PMID- 17494328
TI  - [Investigation of fatty acid composition for identification of clinical isolates
      of Pseudomonas spp].
AB  - The use of commercial test-systems has not allowed to identify 11 atypical
      clinical strains of nonfermenting Gram-negative bacteria. The divergences arised
      not only under their species identification, but also under generic one. On the
      basis of studying the fatty acid composition of the cell wall all isolates were
      referred to Pseudomonas genus. The further control of species belonging of the
      strains carried out with the use of 45 tests and the computer program
      www.imv.kiev.ua/PsmIK/default.htm has confirmed, that five isolates are
      representatives of P. aeruginosa, two ones were identified as P. fluorescens, and
      three more as Pseudomonas spp.

PMID- 17494329
TI  - [Comparative investigation of fructosobisphosphatases of Bacillus subtilis and
      pale-green dwarfism pathogens of cereals in the reaction of double diffusion in
      gel according to Ouchterlony].
AB  - Serological properties of fructosobisphosphatases (FBPases) of Bacillus subtilis
      668 and PGD agent of cereals--the mollicute Acholplasma laidlawii var. granulum
      st. 118 (Alg 118) were studied in a comparative aspect with the help of the
      reaction of double diffusion in gel according to Ouchterlony. It was established
      for each of microorganisms that their extracellular and intracellular enzymes are
      similar in serologic respect, and each of them is composed of two antigens, one
      of them being identical in the both microorganisms, while the other displays only
      partial identity, since it reacts with antibodies in heterological systems with
      formation of a precipitation line looking as a "spur". That indicates to the fact
      that antisera to those enzymes contain antibodies both to general determinants of
      antigens which are compared (FBPases here), and to the determinant absent in one
      of them. Basing on the investigation results it is concluded that FBPase of B.
      subtilis is rather similar than identical, in serological aspect, to the enzyme
      Alg 118 of the same name.

PMID- 17494330
TI  - [Physico-chemical properties of temperate bacteriophage ZF40 of Erwinia
      carotovora].
AB  - A method of efficient purification of the extremely instable virions of the
      temperate bacteriophage ZF40 of Erwinia carotovora was proposed in the work. The
      stage-by-stage centrifugation in mentrizamide and caesium chloride gradients
      permitted to obtain highly purified phage preparations which were used for
      studying the protein composition of the studied erwiniophage. It was established
      that the buoyant density of the phage ZF40 was 1.23 g/cm3, 1.49 g/cm3 and 1.27
      g/cm3 in the gradients of metrizamide, caesium chloride and caesium sulphate,
      respectively. By the polypeptide composition of the virion the phage ZF40 has
      been included in the group of P2-like phages.

PMID- 17494331
TI  - [Nature of the cryptic plasmid pCA25 of Erwinia carotovora subsp. carotovora
      48A].
AB  - High specificity of Tn9 transposition into the cryptic plasmid pCA25 of Erwinia
      carotovora subsp. carotovora 48A was established on the basis of the comparative
      restriction analysis of DNA by endonucleases EcoRV and PstI. Under the extremal
      conditions of growth (1% SDS) the plasmid pCA25:: Tn9 loses about 50 % of
      transpozone sequence, however the cells are not healed of extrachromosomal DNA.
      The inheritance stability, side by side with site-specific transposition and
      deleting of Tn9, confirms a supposition on the prophage origin of
      extrachromosomal element pCA25 of E. carotovora subsp. carotovora 48A.

PMID- 17494332
TI  - [Biosorption ability of mutants of Rhodotorula mucilaginosa UCM Y-1776].
AB  - Twenty stable mutants with various coloration intensity have been allocated in
      carotene-synthesizing natural strain Rhodotorula mucilaginosa UCM Y-1776 (wild
      type) after nitrosoguanidine action. Two brightly orange mutants 4L and 11 and
      one non-pigmented mutant 2 were chosen for the further researches. The
      ultraviolet was inefficient as a mutagen. Resistance to high concentration of
      copper ions (up to 200 mg/g), high sorption ability (Qmax = 9.1 mmol/g) was
      characteristic of R. mucilaginosa UCM Y-1776. Concentration of copper ions 50
      mg/l was toxic for mutants 4L, 11 and 2, which sorption ability was lower in
      comparison with carotene pigmented R. mucilaginosa UCM Y-1776. It was shown, for
      the first time that there was a direct dependence between the presence of
      carotenoid pigments, resistance to high concentration of copper ions and sorption
      ability for yeast R. mucilaginosa UCM Y-1776.

PMID- 17494333
TI  - [Role of Cu, Zn- and Mn-containing superoxide dismutases during the yeast
      Saccharomyces cerevisiae growing on ethanol and glycerol].
AB  - Growth of the yeast Saccharomyces cerevisiae deficient as to superoxidedismutase
      (SOD) genes in the media containing ethanol or glycerol has been investigated. It
      was shown that the role of the two isoforms of SOD was different under conditions
      used in this study. The strain which has only mitochondrial Mn-SOD demonstrated
      higher velocity of culture growth on ethanol compared with the other strains
      investigated. In contrast to that, cytosolic Cu, Zn-SOD played more important
      role under growth on glycerol than Mn-SOD. The levels of carbonyl proteins in SOD
      deficient strains grown on glycerol and in the cells of strain producing only Cu,
      Zn-SOD exposed to inhibitor diethyldithiocarbamate were investigated. The strains
      lacking Mn-SOD and Cu, Zn-SOD demonstrated virtually the same levels of carbonyl
      proteins. It is supposed that Cu, Zn-SOD can compensate Mn-SOD and vice versa.
      Nonlinear correlation between SOD activity and the level of carbonyl proteins was
      found that indicates to the uncertain role of SOD in protein oxidation.

PMID- 17494334
TI  - [Joint cultivation of Bacillus subtilis and Escherichia coli strains promising
      for obtaining complex probiotic].
AB  - The ability of joint cultivation of Bacillus subtilis UCM B-5007 and Escherichia
      coli M-17 in subsurface conditions has been studied. These strains are available
      for creation of a new complex probiotic. Symbiotic relationships between these
      microorganisms were proved. Bacillus subtilis and Escherichia coli strains use
      different growth "strategy". The most optimum ratio of cultures (1:1) for growth,
      biomass accumulation, and for antagonism to test-cultures has been chosen.

PMID- 17494335
TI  - [Optimization of cultivation conditions for strains of Escherichia coli--a
      producer of recombinant alpha-2b-interferon].
AB  - The optimization scheme of cultivation for a strain of Escherichia coli producing
      recombinant alpha-2b-interferon has been developed. The influence of composition
      of a nutrient medium on the level of synthesis of target protein and biomass
      accumulation has been defined. It is experimentally determined that when
      increasing the cultivation time from 8 to 24 hours, the output of recombinant
      alpha-2b-interferon increases twice.

PMID- 17494336
TI  - [Effect of probiotic lactic acid bacteria strains on virus infection].
AB  - The effect of probiotic lactic acid bacteria strains on viral infection was
      studied in experiments in vivo. It was shown that in investigations microbial
      substance based on living cells of L. plantarum and S. salivarius subsp.
      thermophilus strains manifested antiinfluenzal activity under administration of
      0.3 ml of cultural medium per os at a dose of 3 x 10(8)/CFU mouse and
      antiherpetic activity at a dose of 0.3 x 10(9)/CFU mouse. The probiotic
      effectiveness was shown on the model of genital herpes of guinea-pigs at
      concentration of 1 x 10(9) cells/g.p. It was statistically established, that the
      lactic acid bacteria inhibited reproduction of HIV at a dose of cells of 0.1 x
      10(9)/CFU ml.

PMID- 17494337
TI  - [Intein-containing chimeric protein construction and evaluation of its cleavage
      conditions].
AB  - Protein splicing is a post-translational autocatalytic process that results in
      excision of internal peptide (intein) from a precursor protein and the ligation
      of the flanking protein sequences (exteins). High specificity of the intein
      mediated excision of protein precursors allows the use of protein splicing in
      biotechnology. This work was aimed at the obtaining of human growth hormone with
      a native N-terminus in E. coli. Chimerical protein consisting of a short N
      terminal peptide, Mxe GyrA intein and human growth hormone was created. During
      the translation formyl-methionine modified N-terminal peptide should have been
      removed by splicing. Intein was shown to mediate the cleavage of exteins, but
      their subsequent ligation was not observed. That allowed the preparation of human
      growth hormone with a native N-terminus. The effect of various factors on
      cleavage efficiency was studied. The most efficient cleavage of chimeric protein
      (60-80%) was achieved in the presence of inductor (100 mM beta-mercaptoethanol)
      upon the incubation for 4-6 days.

PMID- 17494338
TI  - [Visualization of RNA transcripts with atomic force microscopy].
AB  - RNA transcripts after transcription elongation with T7 RNA polymerase in vitro
      were visualized by using atomic force microscopy (AFM). Fragment of pGEMEX linear
      DNA with the length of 1414 nucleotide pairs carrying promoter and terminator of
      bacteriophage T7 was used as DNA template for transcription. Immobilized on the
      mica (AFM substrate) RNA transcripts formed rod-like condensed structures with
      the length of 122 +/- 10 nm and characteristic aspect ratio ca. 4.5-5. Problems
      of RNA immobilization onto mica for subsequent visualization by AFM are
      discussed.

PMID- 17494339
TI  - [18S-25S rDNA variation in tissue culture of some Gentiana L. species].
AB  - 18S-25S rDNA of intact plants and tissue cultures of G. acaulis, G. punctata and
      G. lutea have been investigated by using blot-hybridization. The decrease of rDNA
      amount was found in the callus cultures as compared with the plants. In contrast
      to other species, G. lutea showed intragenome heterogeneity of rRNA genes as well
      as qualitative rDNA changes in tissue culture, in particular appearance of
      altered repeats. The relationship between the peculiarities of rRNA gene
      structure and their rearrangements in in vitro culture was suggested.

PMID- 17494340
TI  - [Locus Adh and adaptation of cn and vg mutants in the experimental populations of
      Drosophila melanogaster Meig].
AB  - Complex study of adaptation and allozyme belonging of alcoholdehydrogenase (ADH)
      in cn and vg mutants has been carried out in the initial pure lines, in their
      panmixia populations and in condition of substitution of the mutant genotype by
      saturating crossings. It was shown that the high level of adaptation of cn
      mutants and the low level of adaptation of vg mutants was combined with the
      presence of different ADH allozymes. During the saturating crossings the reliable
      coadaptation of the genes cn and Adh(S) as well as vg and Adh(F) was detected
      that confirmes the postulated earlier conception of gene adaptation complexes.

PMID- 17494341
TI  - [The effects of gene Rht8 alleles in agronomic traits of winter bread wheat in
      the conditions of South Steppe of the Ukraine].
AB  - Resistance to frost, winterhardiness, yield and its components were investigated
      in recombinant-inbred lines F5 Odesskaya 16/Bezostaya 1 and 61 winter wheat
      varieties differing on the alleles of Rht8 gene. The absence of influence of gene
      Rht8 different alleles on the tested traits was shown. The high frequency of
      distribution of alleles Rht8c in modern wheat varieties developed in Plant
      Breeding and Genetics Institute is a result of high frequency of use of this
      allele in genetic pool after 1959.

PMID- 17494342
TI  - [Marking of the loci encoding maize resistance to Fusarium].
AB  - Genotyping of F2-population from crossing of maize lines Odesskaya 139 and R221
      contrasting on Fusarium rot resistance has been carried out. Codominant DNA
      marker RGA11 to the locus determining Fusarium resistance was found out at the
      distance of 18.3 cM.

PMID- 17494343
TI  - [Chromosome 11 rearrangements in the different haematological neoplasias].
AB  - The cases of chromosome 11 abnormalities in leukemic bone marrow cells have
      constituted 14.0% in acute lymphoblastic leukemia (ALL), 18.7% in acute myeloid
      leukemia (AML), and 16.7% in refractory anemia (RA). The bands of the short arms
      11p13, 11p14, llp15 and the long arms 11q14, 11q21, 11q23 were involved in
      chromosome rearrangements. The rearrangements of the band 11q23 were detected
      more often. Reciprocal translocations were found with the highest frequency,
      while para- and pericentic invertions, terminal and intestitial deletions occured
      with the lower incidence. Deletions were found in RA cases only. Comparison with
      the clinical features showed no correlation with the age and the main
      haematological indexes including the amount of blast cells in the initial period.
      The results have showed the poor prognosis of the abnormalities not only of
      11q21, 11q23 in acute leukemia (AL), but of 11p13, 11p15 in AML as well, while
      not enough data on this subject is availalbe in the literature.

PMID- 17494344
TI  - [The karyological features of the genus Planorbarius (Gastropoda, Pulmonata,
      Bulinidae) of the Ukrainian fauna].
AB  - The absence of significant distinctions between the species of the genus
      Planorbarius in the narrow sense (P. corneus, P. banaticus, P. purpura and P.
      grandis) has been established. All investigated species had identical chromosomal
      formulas (2n = 30m + 6sm = 36) and fundamental numbers (FN=72). Reliable
      distinctions between them were not found by total complement length (TCL),
      relative length of chromosomes (RL) and centromeric indexes. The species selected
      on the basis of genetic marking differed clearly by centromeric index of
      chromosome 12 that confirms the allospecies frame of P. corneus s. lato.

PMID- 17494345
TI  - The micronucleus assay in exfoliated human cells: a mini-review of papers from
      the CIS.
AB  - The critical analysis of the data concerning micronucleus assay in exfoliated
      epithelial cells presented by the investigators from the CIS is carried out.
      Twenty two articles are evaluated, and shortcomings of some of them are
      discussed. Presented results are compared whenever possible with literature data.
      The aim of the mini-review is a criticism of shortcomings of the papersforfurther
      improvement of the presentation of the data on micronucleus assay which will give
      the possibility to compare the results with the data presented by foreign
      investigators.

PMID- 17494346
TI  - [Molecular-genetic mechanisms of plant resistance to viruses].
AB  - This paper gives a brief overview of the recent ideas about molecular and genetic
      mechanisms of plant resistance to viruses. Two plant antiviral strategies (R-gene
      mediated mechanism and RNA-silencing) are considered. Examples of engineered
      virus resistance are presented.

PMID- 17494347
TI  - Turning over in their suites. At 15%, hospital CEO turnover has barely wavered in
      the past five years, and it's expected to stay that way for a while.
AB  - Hospitals saw nearly the same rate of turnover among CEOs last year-15%-as
      they've experienced in the previous five years, according to the American College
      of Healthcare Executives. But some say that's too high, and the industry has
      begun taking some measures to retain their top execs. Consultant Jim Nelson,
      left, says recently he's seen more hospitals offering incentives for CEOs to stay
      than in all prior years.

PMID- 17494348
TI  - Boost for Medicare Advantage. Congress questions why plans getting payment raise.

PMID- 17494349
TI  - NPI deadline postponed. CMS grants more time to comply with identifier rule.

PMID- 17494350
TI  - CMS tries cash this time. New quality reporting program has financial incentives.

PMID- 17494351
TI  - Premier eyes improved analysis tools with deal. CareScience's database,
      management will be merged within 90 days.

PMID- 17494352
TI  - Joining forces in Milwaukee. Froedtert, Columbia deal could hurt Wheaton.

PMID- 17494353
TI  - Proposed hospital raises ire. Buffalo plan called 'premature' by state health
      official.

PMID- 17494354
TI  - Popping the cost balloon. Angioplasty study should be a harbinger, but budgets,
      entropy stall reform.

PMID- 17494355
TI  - Measures aren't everything. Creating a safe hospital is a lasting, open process
      across the whole enterprise.

PMID- 17494356
TI  - Remote possibilities. Rural communities seek creative solutions as they grapple
      with a nurse shortage that's particularly acute outside metro areas.

PMID- 17494357
TI  - The 'other' category. Hospitals turn to IT systems outside the financial and
      clinical realms.

PMID- 17494358
TI  - By the numbers. Largest national healthcare associations. Organizations ranked by
      2005 revenue, with noted exceptions. Based on Modern Healthcare's review of IRS
      form 990 filings.

PMID- 17494359
TI  - Hospitalist business enters new stage. Some companies buying smaller rivals;
      others grow through contracting.

PMID- 17494360
TI  - From temperance to alcoholism in America.

PMID- 17494362
TI  - An ethicist's commentary on client financial status and treatment.

PMID- 17494361
TI  - Contradicting a unitary theory of general anesthetic action: a history of three
      compounds from 1901 to 2001.

PMID- 17494363
TI  - Nothing to fear, but...part I: the clinician and fear of physical harm.

PMID- 17494364
TI  - Veterinary medicine for a world in crisis.

PMID- 17494365
TI  - Neuronal vacuolation in an adult ferret.
AB  - The brain of a ferret showing abnormal neurologic signs was evaluated by
      histopathologic, histochemical, immunohistochemical, and ultrastructural
      examinations. Extensive neuronal vacuolation was observed. Since the brain was
      negative for protease-resistant protein prion (PrP'"), it was concluded that this
      was not a case of transmissible spongiform encephalopathy.

PMID- 17494366
TI  - Radiographic and functional evaluation of dogs at least 1 year after tibial
      plateau leveling osteotomy.
AB  - The progression of osteoarthritis and clinical function in 29 dogs at least 1
      year after tibial plateau leveling osteotomy was evaluated. A previously reported
      radiographic scoring system was used by 3 investigators to evaluate preoperative
      and postoperative radiographs for evidence of stifle osteoarthritis. The combined
      scores were then used to evaluate the progression of osteoarthritis. The
      difference between the preoperative scores, derived from radiographs taken at the
      time of surgery, and the postoperative scores based on radiographs taken at least
      1 year later was modest but statistically significant. Despite this finding,
      client satisfaction was very good. Clinical function was assessed by using a
      previously reported client questionnaire. According to owner assessment at least
      1 year after surgery, there was a significant improvement in function after
      tibial plateau leveling osteotomy when compared with the preoperative status.
      Improvement in function as measured by the client questionnaire did not
      significantly predict the radiographic osteoarthritis score.

PMID- 17494368
TI  - Portacaval shunt in a calf: clinical, pathologic, and ultrasonographic findings.
AB  - A calf with a previous history of lameness was presented for weakness and
      anorexia. Increased liver enzymes and difficulty in assessing the portal system
      by ultrasonography were compatible with liver disease. Doppler ultrasonography
      revealed an extrahepatic portacaval shunt. This is the first ultrasonographic
      description of extrahepatic portacaval shunt in a ruminant.

PMID- 17494367
TI  - Seroprevalence of and agroecological risk factors for Mycobacterium avium
      subspecies paratuberculosis and neospora caninum infection among adult beef
      cattle in cow-calf herds in Alberta, Canada.
AB  - A province-wide cross-sectional seroprevalence and agroecological risk factor
      study of Mycobacterium avium subspecies paratuberculosis (MAP) and Neospora
      caninum (NC) infection among cattle in 100 cow-calf herds in Alberta was
      conducted. The seroprevalence of MAP in adult cattle was 1.5% across all herds.
      Using a widely accepted herd test cutpoint of 2 or more seropositive cows out of
      30 animals tested, 7.9% of herds were estimated to be infected (95% confidence
      interval (CI): 2.3-23.4%). Seroprevalence of MAP differed by agroecological
      region; specifically, cattle and herds in areas with high soil pH (> 7.0),
      southern latitudes, and arid climates had a moderately reduced risk of infection
      (P < 0.10). Seroprevalence of NC infection was 9.7% among adult beef cattle
      province-wide--these levels also varied by agroecological region--with 91.0% of
      herds infected overall.

PMID- 17494369
TI  - Successful treatment of nasal sporotrichosis in a dog.
AB  - Sporotrichosis is an uncommon mycosis of dogs caused by Sporothrix schenckii.
      This report details the diagnosis and treatment of intranasal sporotrichosis in a
      dog presented for a loss of smell, sneezing, and nasal congestion. Following 6
      months of itraconazole treatment, a computed tomography scan showed a complete
      resolution of previously identified abnormalities.

PMID- 17494370
TI  - Use of grid keratotomy for the treatment of indolent corneal ulcer in a llama.
AB  - A case of indolent corneal ulcer in a llama (Llama glama) is described.
      Diagnostic testing included a complete ophthalmic examination with corneal
      cytologic and histopathologic examination. Successful management involved grid
      keratotomy and topical application of neomycin-polymixin-bacitracin and atropine
      1% ointments. Weekly follow-up examinations are described until healing was
      considered complete.

PMID- 17494371
TI  - Congenital colonic malformation ("short colon") in a 4-month-old standardbred
      foal.
AB  - During exploratory laparotomy of a foal with colic, a congenital abnormally
      developed large colon was identified incidentally. Long-term follow-up showed
      that the colt was more prone to gas-colic with diet and exercise changes than
      were other horses, due possibly to the short colon.

PMID- 17494372
TI  - Liver lobe torsion in a dog.
AB  - Abdominal radiographs of a dog presented for anorexia and vomiting revealed an
      ill-defined increase in opacity caudal to the stomach and caudal displacement of
      the small intestines. Ultrasonographs revealed an enlarged liver lobe with
      vascular thrombosis. Left medial liver lobe torsion was confirmed at postmortem.

PMID- 17494373
TI  - Pelvic fractures.

PMID- 17494375
TI  - Penile hematoma in a Shami buck.

PMID- 17494374
TI  - Veterinary diagnostic imaging.

PMID- 17494376
TI  - Love is a two-way street.

PMID- 17494377
TI  - Recommended vs. alternative treatment options: is one enough?

PMID- 17494378
TI  - Practice management can make a difference.

PMID- 17494379
TI  - In the beginning...
AB  - Dentists have a number of important practice management decisions to make at the
      beginning of their careers. These are often made without a lot of training in the
      business side of dental practice. They include knowledge of what to say to get
      offered the right job and what to ask to choose the best position. New dentists
      need to look inward first and be proactive next to land the best position
      possible.

PMID- 17494380
TI  - Feel like giving up and getting out... from beneath the mid-career squeeze?
AB  - Mid-career provides different opportunities and challenges for different
      dentists. Some are hitting their stride and enjoying success. Others are facing
      financial worries and multiple concerns. While many of the issues that mid-career
      practices experience can be addressed effectively, doing so requires looking
      closely at those areas that tend to be the most troublesome, including patient
      retention, staff hiring and training, and patient satisfaction. If practices take
      measurable steps to address those areas, they make great strides in overcoming
      the mid-career slump.

PMID- 17494381
TI  - Smart approach to practice transition: options and strategies.
AB  - This material discusses contemporary approaches to practice transition for
      practice owners. Although this discussion is not intended to be comprehensive, it
      is intended to provide a good overview in the form of a structured outline of
      selected areas an owner should think about and undertake to implement, as
      appropriate, to their practice and their goals.

PMID- 17494383
TI  - The war against Mother Nature and Father Time.

PMID- 17494382
TI  - A history of arsenic in dentistry.
AB  - The history of the use of arsenic in dentistry has been relegated to dental
      history. Once hailed as a panacea for the relief of pain and the answer to root
      canal therapy, it soon fell out of use mainly because of its misuse by unskilled
      and unscrupulous dentists in search of a quick fix to a complex problem. Such is
      the story of arsenic.

PMID- 17494384
TI  - Optimal scales to observe habitat dynamics: a coral reef example.
AB  - A new technique to estimate the characteristic length scales (CLSs) of real
      ecological systems provides an objective means to identify the optimal scale(s)
      of observation to best detect underlying dynamical trends. Application of the
      technique to natural systems has focused on identifying appropriate scales to
      measure the dynamics of species as descriptors of community and ecosystem
      dynamics. However, ecosystem monitoring is often based not on assessing single
      species, but on species assemblages, functional groups, or habitat types. We
      asked whether the concept of CLSs based on dynamic interactions among species
      could be extended to examine interactions among habitat types and thus to
      identify optimal scales for observing habitat dynamics. A time series of three
      spatial maps of benthic habitats on a Caribbean coral reef was constructed from
      aerial photographs, Compact Airborne Spectrographic Imager (CASI) images, and
      IKONOS satellite images, providing the short time sequence required for this
      technique. We estimated the CLS based on the dynamics of three distinct habitat
      types: dense stands of seagrass, sparse stands of seagrass, and Montastrea patch
      reefs. Despite notable differences in the areal extent of and relative change in
      these habitats over the 21-year observation period, analyses based on each
      habitat type indicated a similar CLS of -300 m. We interpret the consistency of
      CLSs among habitats to indicate that the dynamics of the three habitat types are
      linked. The results are encouraging, and they indicate that CLS techniques can be
      used to identify the appropriate scale at which to monitor ecosystem trends on
      the basis of the dynamics of only one of a disparate suite of habitat types.

PMID- 17494385
TI  - Birds transport nutrients to fragmented forests in an urban landscape.
AB  - The influence of urbanization on nutrient cycling is vaguely known. Here we
      document that birds, especially those increasing in urban areas (such as crows,
      Corvus macrorhynchos and C. corone), affect nutrient cycles. Using fecal traps,
      we measured phosphorus (P) and nitrogen (N) input from the excrement of birds in
      fragmented forests in an urban landscape. Sources of avian feces were examined on
      the basis of carbon (C), N, and P percentages and stable isotopes of delta15N and
      delta13C. Nitrogen and P input was aggregated in the urban landscape, being
      especially high at the forest where crows roosted during winter. The annual P
      input due to bird droppings (range 0.068-0.460 kg x ha(-1) x yr(-1); mean 0.167
      kg x ha(-1) x yr(-1)) was 12.4% of the total of other pathways in typical forests
      and 52.9% in the evergreen forest where crows roosted. The annual N input due to
      bird droppings (range 0.44-3.49 kg x ha(-1) x yr(-1); mean 1.15 kg x ha(-1) x yr(
      1)) was 5.2% of the total of other pathways in typical forests and 27.0% in the
      evergreen forest used by roosting crows. Expected sources of nutrients in feces
      included insects in the breeding season, fruits in autumn, and mammals and birds
      in winter. Stable isotopes suggested that the source of nutrients in forests used
      by roosting crows was from outside the forest. Therefore, birds played a
      significant role as transporters of nutrients from garbage (including fish,
      livestock, and/or C4 plants such as corn, with high delta15N and delta13C) in
      residential and business areas to fragmented evergreen forests, especially near
      their winter roosts.

PMID- 17494386
TI  - Evaluating an invasive species policy: ballast water exchange in the Great Lakes.
AB  - Improvements in environmental policy require an accurate diagnosis of the
      shortcomings of existing policy. We develop a model for assessing the efficacy of
      policy instruments aimed at reducing the introduction of nonindigenous species.
      The model identifies and accounts for several features of the nonindigenous
      species introduction-detection process that complicate interpretations of
      monitoring data. Specifically, the model includes explicit attention to the
      pathway of introduction, a probabilistic description of species detection, and
      the possibility of attenuation of species introductions over time. We apply this
      theoretical model to the case of mid-ocean ballast water exchange, which was
      implemented by the United States in 1990 for the North American Great Lakes.
      Contrary to other authors who take the recent increase in discoveries of
      nonindigeneous species (NIS) in the Great Lakes as evidence that ballast water
      exchange is ineffective, we find that the observed detection record could just as
      plausibly be explained by a lag of a few years between introduction and
      detection, even if ballast water exchange was 100% effective. Model results
      suggest that, under current monitoring regimes, several more years of data would
      be required to make a conclusive evaluation of ballast water exchange. Better
      estimation of the lag time between introduction and detection, and a shortening
      of that lag time with better monitoring, would allow more precise and timely
      evaluation of the efficacy of ballast water exchange and other policy
      instruments.

PMID- 17494387
TI  - Predicting invasion risk using measures of introduction effort and environmental
      niche models.
AB  - The Chinese mitten crab (Eriocheir sinensis) is native to east Asia, is
      established throughout Europe, and is introduced but geographically restricted in
      North America. We developed and compared two separate environmental niche models
      using genetic algorithm for rule set prediction (GARP) and mitten crab
      occurrences in Asia and Europe to predict the species' potential distribution in
      North America. Since mitten crabs must reproduce in water with >15% per hundred
      salinity, we limited the potential North American range to freshwater habitats
      within the highest documented dispersal distance (1260 km) and a more restricted
      dispersal limit (354 km) from the sea. Applying the higher dispersal distance,
      both models predicted the lower Great Lakes, most of the eastern seaboard, the
      Gulf of Mexico and southern extent of the Mississippi River watershed, and the
      Pacific northwest as suitable environment for mitten crabs, but environmental
      match for southern states (below 35 degrees N) was much lower for the European
      model. Use of the lower range with both models reduced the expected range,
      especially in the Great Lakes, Mississippi drainage, and inland areas of the
      Pacific Northwest. To estimate the risk of introduction of mitten crabs, the
      amount of reported ballast water discharge into major United States ports from
      regions in Asia and Europe with established mitten crab populations was used as
      an index of introduction effort. Relative risk of invasion was estimated based on
      a combination of environmental match and volume of unexchanged ballast water
      received (July 1999-December 2003) for major ports. The ports of Norfolk and
      Baltimore were most vulnerable to invasion and establishment, making Chesapeake
      Bay the most likely location to be invaded by mitten crabs in the United States.
      The next highest risk was predicted for Portland, Oregon. Interestingly, the port
      of Los Angeles/Long Beach, which has a large shipping volume, had a low risk of
      invasion. Ports such as Jacksonville, Florida, had a medium risk owing to small
      shipping volume but high environmental match. This study illustrates that the
      combination of environmental niche- and vector-based models can provide managers
      with more precise estimates of invasion risk than can either of these approaches
      alone.

PMID- 17494388
TI  - Life-cycle assessment of net greenhouse-gas flux for bioenergy cropping systems.
AB  - Bioenergy cropping systems could help offset greenhouse gas emissions, but
      quantifying that offset is complex. Bioenergy crops offset carbon dioxide
      emissions by converting atmospheric CO2 to organic C in crop biomass and soil,
      but they also emit nitrous oxide and vary in their effects on soil oxidation of
      methane. Growing the crops requires energy (e.g., to operate farm machinery,
      produce inputs such as fertilizer) and so does converting the harvested product
      to usable fuels (feedstock conversion efficiency). The objective of this study
      was to quantify all these factors to determine the net effect of several
      bioenergy cropping systems on greenhouse-gas (GHG) emissions. We used the DAYCENT
      biogeochemistry model to assess soil GHG fluxes and biomass yields for corn,
      soybean, alfalfa, hybrid poplar, reed canarygrass, and switchgrass as bioenergy
      crops in Pennsylvania, USA. DAYCENT results were combined with estimates of
      fossil fuels used to provide farm inputs and operate agricultural machinery and
      fossil-fuel offsets from biomass yields to calculate net GHG fluxes for each
      cropping system considered. Displaced fossil fuel was the largest GHG sink,
      followed by soil carbon sequestration. N20 emissions were the largest GHG source.
      All cropping systems considered provided net GHG sinks, even when soil C was
      assumed to reach a new steady state and C sequestration in soil was not counted.
      Hybrid poplar and switchgrass provided the largest net GHG sinks, >200 g CO2e-C x
      m(-2) x yr(-1) for biomass conversion to ethanol, and >400 g CO2e-C x m(-2) x yr(
      1) for biomass gasification for electricity generation. Compared with the life
      cycle of gasoline and diesel, ethanol and biodiesel from corn rotations reduced
      GHG emissions by approximately 40%, reed canarygrass by approximately 85%, and
      switchgrass and hybrid poplar by approximately 115%.

PMID- 17494389
TI  - Net primary production of Chinese croplands from 1950 to 1999.
AB  - Considerable efforts have been made to assess the contribution of forest and
      grassland ecosystems to the global carbon budget, while less attention has been
      paid to agriculture. Net primary production (NPP) of Chinese croplands and
      driving factors are seldom taken into account in the regional carbon budget. We
      studied crop NPP by analyzing the documented crop yields from 1950 to 1999 on a
      provincial scale. Total NPP, including estimates of the aboveground and
      belowground components, was calculated from harvested yield data by (1)
      conversion from economic yield of the crop to aboveground mass using the ratio of
      aboveground residue production to the economic yield, (2) estimation of
      belowground mass as a function of aboveground mass, and (3) conversion from total
      dry mass to carbon mass. This approach was applied to 13 crops, representing
      86.8% of the total harvested acreage of crops in China. Our results indicated
      that NPP in Chinese croplands increased markedly during this period. Averaging
      for each decade, the amount of NPP was 146 +/- 32, 159 +/- 34, 260 +/- 55, 394 +/
      85, and 513 +/- 111 Tg C/yr (mean +/- SD) in the 1950s, 1960s, 1970s, 1980s, and
      1990s, respectively. This increase may be attributed to synthetic fertilizer
      application. A further investigation indicated that the climate parameters of
      temperature and precipitation determined the spatial variability in NPP.
      Spatiotemporal variability in NPP can be well described by the consumption of
      synthetic fertilizer and by climate parameters. In addition, the total amount of
      residue C and root C retained by the soils was estimated to be 618 Tg, with a
      range from 300 to 1040 Tg over the 50 years.

PMID- 17494390
TI  - Using nocturnal cold air drainage flow to monitor ecosystem processes in complex
      terrain.
AB  - This paper presents initial investigations of a new approach to monitor ecosystem
      processes in complex terrain on large scales. Metabolic processes in mountainous
      ecosystems are poorly represented in current ecosystem monitoring campaigns
      because the methods used for monitoring metabolism at the ecosystem scale (e.g.,
      eddy covariance) require flat study sites. Our goal was to investigate the
      potential for using nocturnal down-valley winds (cold air drainage) for
      monitoring ecosystem processes in mountainous terrain from two perspectives:
      measurements of the isotopic composition of ecosystem-respired CO2 (delta13C(ER))
      and estimates of fluxes of CO2 transported in the drainage flow. To test if this
      approach is plausible, we monitored the wind patterns, CO2 concentrations, and
      the carbon isotopic composition of the air as it exited the base of a young
      (approximately 40 yr-old) and an old (>450 yr-old) steeply sided Douglas-fir
      watershed. Nocturnal cold air drainage within these watersheds was strong, deep,
      and occurred on more than 80% of summer nights. The depth of cold air drainage
      rapidly increased to tower height or greater when the net radiation at the top of
      the tower approached zero. The carbon isotope composition of CO2 in the drainage
      system holds promise as an indicator of variation in basin-scale physiological
      processes. Although there was little vertical variation in CO2 concentration at
      any point in time, we found that the range of CO2 concentration over a single
      evening was sufficient to estimate delta 13C(ER) from Keeling plot analyses. The
      seasonal variation in delta 13C(ER) followed expected trends: during the summer
      dry season delta 13C(ER) became less negative (more enriched in 13C), but once
      rain returned in the fall, delta 13C(ER) decreased. However, we found no
      correlation between recent weather (e.g., vapor pressure deficit) and delta
      13C(ER) either concurrently or with up to a one-week lag. Preliminary estimates
      suggest that the nocturnal CO2 flux advecting past the 28-m tower is a rather
      small fraction (<20%) of the watershed-scale respiration. This study demonstrates
      that monitoring the isotopic composition and CO2 concentration of cold air
      drainage at the base of a watershed provides a new tool for quantifying ecosystem
      metabolism in mountainous ecosystems on the basin scale.

PMID- 17494391
TI  - Coupling ecology and GIS to evaluate efficacy of marine protected areas in
      Hawaii.
AB  - In order to properly determine the efficacy of marine protected areas (MPAs), a
      seascape perspective that integrates ecosystem elements at the appropriate
      ecological scale is necessary. Over the past four decades, Hawaii has developed a
      system of 11 Marine Life Conservation Districts (MLCDs) to conserve and replenish
      marine resources around the state. Initially established to provide opportunities
      for public interaction with the marine environment, these MLCDs vary in size,
      habitat quality, and management regimes, providing an excellent opportunity to
      test hypotheses concerning MPA design and function using multiple discrete
      sampling units. Digital benthic habitat maps for all MLCDs and adjacent habitats
      were used to evaluate the efficacy of existing MLCDs using a spatially explicit
      stratified random sampling design. Analysis of benthic cover validated the a
      priori classification of habitat types and provided justification for using these
      habitat strata to conduct stratified random sampling and analyses of fish habitat
      utilization patterns. Results showed that a number of fish assemblage
      characteristics (e.g., species richness, biomass, diversity) vary among habitat
      types, but were significantly higher in MLCDs compared with adjacent fished areas
      across all habitat types. Overall fish biomass was 2.6 times greater in the MLCDs
      compared to open areas. In addition, apex predators and other species were more
      abundant and larger in the MLCDs, illustrating the effectiveness of these
      closures in conserving fish populations within their boundaries. Habitat type,
      protected area size, and level of protection from fishing were all important
      determinates of MLCD effectiveness with respect to their associated fish
      assemblages. Although size of these protected areas was positively correlated
      with a number of fish assemblage characteristics, all appear too small to have
      any measurable influence on the adjacent fished areas. These protected areas were
      not designed for biodiversity conservation or fisheries enhancement yet still
      provide varying degrees of protection for fish populations within their
      boundaries. Implementing this type of biogeographic process, using remote sensing
      technology and sampling across the range of habitats present within the seascape,
      provides a robust evaluation of existing MPAs and can help to define ecologically
      relevant boundaries for future MPA design in a range of locations.

PMID- 17494392
TI  - Directional selection by fisheries and the timing of sockeye salmon (Oncorhynchus
      nerka) migrations.
AB  - The timing of migration from feeding to breeding areas is a critical link between
      the growth and survival of adult animals, their reproduction, and the fitness of
      their progeny. Commercial fisheries often catch a large fraction of the migrants
      (e.g., salmon), and exploitation rates can vary systematically over the fishing
      season. We examined daily records of sockeye salmon (Oncorhynchus nerka) in the
      Egegik and Ugashik management districts in Bristol Bay, Alaska (USA), for
      evidence of such temporally selective fishing. In recent years, the early
      migrants have experienced lower fishing rates than later migrants, especially in
      the Egegik district, and the median migration date of the fish escaping the
      fisheries has been getting progressively earlier in both districts. Moreover, the
      overall runs (catch and escapement) in the Egegik district and, to a lesser
      extent the Ugashik district, have been getting earlier, as predicted in response
      to the selection on timing. The trends in timing were not correlated with sea
      surface temperature in the region of the North Pacific Ocean where the salmon
      tend to concentrate, but the trends in the two districts were correlated with
      each other, indicating that there may be some common environmental influence in
      addition to the effect of selection. Despite the selection, both groups of salmon
      have remained productive. We hypothesize that this resilience may result from
      representation of all component populations among the early and late migrants, so
      that the fisheries have not eliminated entire populations, and from density
      dependent processes that may have helped maintain the productivity of these
      salmon populations.

PMID- 17494393
TI  - Macroinvertebrate production and food web energetics in an industrially
      contaminated stream.
AB  - This study examines secondary production and periphyton-invertebrate food web
      energetics at two sites in an industrially contaminated, nutrient-enriched
      stream. Secondary production data and data from the literature were used to
      calculate potential amounts of mercury transferred from periphyton to chironomid
      larvae and into terrestrial food webs with emerging adults. The nutritional
      quality of periphyton was characterized using energy content, chlorophyll a,
      protein, ash-free dry mass (AFDM), and percentage of organic matter. Chironomid
      larvae (Orthocladiinae: Cricotopus spp.) comprised 96% of all macroinvertebrates
      collected from stones at the two sites. Cricotopus production was extremely high:
      production was 59.5 g AFDM x m(-2) x yr(-1) at the site upstream of a 1-ha
      settling basin and 32.4 g AFDM x m(-2) x yr(-1) at the site below the basin.
      Apparent differences in annual secondary production were associated with reduced
      organic content (i.e., nutritional quality) of the periphyton matrix under
      different loading of total suspended solids. The periphyton matrix at both sites
      was contaminated with inorganic (Hg(II)) and methyl (MeHg) mercury. The amount of
      Hg(II) potentially ingested by Cricotopus was calculated to be 49 mg Hg(II) x m(
      1) x yr(-1) at the upstream site and 19 mg Hg(II)x m(-2) x yr(-1) at the
      downstream site. Mercury ingestion by Cricotopus at the downstream site was
      calculated to be 2% of the estimated annual deposition of particulate-bound
      Hg(II) to the stream bed. Emergence of adult Cricotopus was calculated to remove
      563 microg Hg(II)x m(-2) x yr(-1) from the stream at the upstream site and 117
      microg Hg(II) x m(-2) x yr(-1) at the downstream site, which amounted to 4.1 g
      Hg(II)/yr for the 2.1-km reach of stream included in this study. The ratio of
      metal export in emergence production to surface area for the study stream was 10
      to 10(3) times higher than ratios calculated for lakes using data from the
      literature. This study is the first well-documented example of extremely high
      aquatic insect production in an industrially contaminated, nutrient-enriched
      stream, and it highlights the application of production measurements to examine
      the role of aquatic insect production in the trophic transfer of energy and
      persistent contaminants in aquatic food webs and into terrestrial food webs.

PMID- 17494394
TI  - Historical metal concentrations in lacustrine food webs revealed using fossil
      ephippia from Daphnia.
AB  - Metal contamination of freshwater ecosystems is increasingly prevalent due to
      anthropogenic activities such as metal smelting and fossil fuel combustion. While
      toxicological studies focus on aqueous metal concentrations that result in lethal
      or sublethal responses, currently the only method for reconstructing a lake's
      metal contamination history is through an examination of the sedimentary
      deposits. In this paper, we suggest that cladoceran diapausing eggs (ephippia),
      which are abundant in nature and accumulate maternally derived metals, can be
      used to measure historical variations in biologically relevant metals that derive
      from the water column (water, diet). Linear regressions of total metal content
      against ephippia density or mass were strong (R2 > 0.80, P < 0.04) and revealed
      that metals were incorporated into ephippia with little contamination from the
      sediment matrix. Comparison of metal concentrations in ephippia and bulk
      sediments from three lakes demonstrated that some metals associated with urban
      sources (Cd, Cr, Mo) were preferentially concentrated in ephippia, whereas
      concentrations of other metals indicating landscape erosion (Al, Ca, Fe, Mn)
      exhibited greater concentrations in bulk sediments than in diapausing eggs.
      Because historical changes in metals within fossils and bulk sediments were
      uncorrelated in most instances, past variation in the metal content of ephippia
      provided a unique history of food web exposure to metals in the water column.

PMID- 17494395
TI  - Historical eutrophication in a river-estuary complex in mid-coast Maine.
AB  - European settlement of New England brought about a novel disturbance regime that
      impacted rivers and estuaries through overfishing, deforestation, dams, and water
      pollution. The negative consequences of these activities intensified with
      industrialization in the 19th and 20th centuries, often resulting in ecosystem
      degradation. Since environmental legislation was implemented in the 1970s,
      improvement in water quality has been tangible and widespread; however,
      ecological recovery can require substantial amounts of time and may never be
      complete. To document the natural baseline conditions and investigate the
      recovery of a severely degraded river-estuary complex in mid-coast Maine, we
      examined diatoms, pollen, total organic carbon, total nitrogen, stable isotopes,
      total phosphorus, biogenic silica, and trace metals in intertidal sediments and
      established a chronology with 14C, 210Pb, and indicator pollen horizons. Both
      climate variability and human effects were evident in the sedimentary record of
      Merrymeeting Bay, the freshwater tidal portion of the Kennebec estuary. Natural
      climate variability was apparent in an episode of high sedimentation and altered
      diatom abundance during the 12th and 13th centuries and in changing pollen
      abundances between the 16th and 19th centuries, indicative of regional cooling.
      During the 18th century, colonial land clearance began an era of high
      sedimentation and eutrophication that strongly intensified with industrialization
      during the late 19th and 20th centuries. Improvements in water quality over the
      past 30 years in response to environmental regulation had little effect on
      ecosystem recovery as represented by the sedimentary record. Diatom composition
      and productivity and high fluxes of organic C, total P, and biogenic Si in recent
      sediments indicate that rates of nutrient loading remain high. These
      environmental proxies imply that aquatic productivity in Merrymeeting Bay was
      originally nutrient limited and water clarity high, relative to today. Further
      recovery may require more stringent regulation of nutrient inputs from industrial
      and municipal point sources. This historical study can contribute to public
      debate about the environmental management of this unusual river-estuary complex
      by describing its long-term natural baseline, thereby illustrating the upper
      limit of its potential for recovery.

PMID- 17494396
TI  - Evidence, exaggeration, and error in historical accounts of chaparral wildfires
      in California.
AB  - For more than half a century, ecologists and historians have been integrating the
      contemporary study of ecosystems with data gathered from historical sources to
      evaluate change over broad temporal and spatial scales. This approach is
      especially useful where ecosystems were altered before formal study as a result
      of natural resources management, land development, environmental pollution, and
      climate change. Yet, in many places, historical documents do not provide precise
      information, and pre-historical evidence is unavailable or has ambiguous
      interpretation. There are similar challenges in evaluating how the fire regime of
      chaparral in California has changed as a result of fire suppression management
      initiated at the beginning of the 20th century. Although the firestorm of October
      2003 was the largest officially recorded in California (approximately 300,000
      ha), historical accounts of pre-suppression wildfires have been cited as evidence
      that such a scale of burning was not unprecedented, suggesting the fire regime
      and patch mosaic in chaparral have not substantially changed. We find that the
      data do not support pre-suppression megafires, and that the impression of large
      historical wildfires is a result of imprecision and inaccuracy in the original
      reports, as well as a parlance that is beset with hyperbole. We underscore themes
      of importance for critically analyzing historical documents to evaluate
      ecological change. A putative 100 mile long by 10 mile wide (160 x 16 km)
      wildfire reported in 1889 was reconstructed to an area of chaparral approximately
      40 times smaller by linking local accounts to property tax records, voter
      registration rolls, claimed insurance, and place names mapped with a geographical
      information system (GIS) which includes data from historical vegetation surveys.
      We also show that historical sources cited as evidence of other large chaparral
      wildfires are either demonstrably inaccurate or provide anecdotal information
      that is immaterial in the appraisal of pre-suppression fire size. Since
      historical evidence is inadequate for reconstructing a statistical distribution
      of pre-suppression fire sizes to compare with post-suppression data, other more
      propitious methods of evaluating change are discussed.

PMID- 17494397
TI  - Assessing the risk of ignition in the Russian far east within a modeling
      framework of fire threat.
AB  - The forests of high biological importance in the Russian Far East (RFE) have been
      experiencing increasing pressure from growing demands for natural resources under
      the changing economy of post-Soviet Russia. This pressure is further amplified by
      the rising threat of large and catastrophic fire occurrence, which threatens both
      the resources and the economic potential of the region. In this paper we
      introduce a conceptual Fire Threat Model (FTM) and use it to provide quantitative
      assessment of the risk of ignition in the Russian Far East. The remotely sensed
      data driven FTM is aimed at evaluating potential wildland fire occurrence and its
      impact and recovery potential for a given resource. This model is intended for
      use by resource managers to assist in assessing current levels of fire threat to
      a given resource, projecting the changes in fire threat under changing climate
      and land use, and evaluating the efficiency of various management approaches
      aimed at minimizing the fire impact. Risk of ignition (one of the major
      uncertainties within fire threat modeling) was analyzed using the MODIS active
      fire product. The risk of ignition in the RFE is shown to be highly variable in
      spatial and temporal domains. However, the number of ignition points is not
      directly proportional to the amount of fire occurrence in the area. Fire
      ignitions in the RFE are strongly linked to anthropogenic activity
      (transportation routes, settlements, and land use). An increase in the number of
      fire ignitions during summer months could be attributed to (1) disruption of the
      summer monsoons and subsequent changes in fire weather and (2) an increase in
      natural sources of fire ignitions.

PMID- 17494398
TI  - Forest floor depth mediates understory vigor in xeric Pinus palustris ecosystems.
AB  - Longleaf pine (Pinus palustris) woodlands and savannas are among the most
      frequently burned ecosystems in the world with fire return intervals of 1-10
      years. This fire regime has maintained high levels of biodiversity in terms of
      both species richness and endemism. Land use changes have reduced the area of
      this ecosystem by >95%, and inadequate fire frequencies threaten many of the
      remnants today. In the absence of frequent fire, rapid colonization of hardwoods
      and shrubs occurs, and a broad-leaved midstory develops. This midstory
      encroachment has been the focus of much research and management concern, largely
      based on the assumption that the midstory reduces understory plant diversity
      through direction competition via light interception. The general application of
      this mechanism of degradation is questionable, however, because midstory density,
      leaf area, and hardwood species composition vary substantially along a soil
      moisture gradient from mesic to extremely xeric sites. Reanalysis of recently
      reported data from xeric longleaf pine communities suggests that the development
      of the forest floor, a less conspicuous change in forest structure, might cause a
      decline in plant biodiversity when forests remain unburned. We report here a test
      of the interactions among fire, litter accumulation, forest floor development,
      and midstory canopy density on understory plant diversity. Structural equation
      modeling showed that within xeric sites, forest floor development was the primary
      factor explaining decreased biodiversity. The only effects of midstory
      development on biodiversity were those mediated through forest floor development.
      Boundary line analysis of functional guilds of understory plants showed
      sensitivity to even minor development of the forest floor in the absence of fire.
      These results challenge the prevailing management paradigm and suggest that
      within xeric longleaf pine communities, the primary focus of managed fire regime
      should be directed toward the restoration of forest floor characteristics rather
      than the introduction of high-intensity fires used to regulate midstory
      structure.

PMID- 17494399
TI  - Relevance of rangeland degradation in semiarid northeastern South Africa to the
      nonequilibrium theory.
AB  - According to the nonequilibrium theory, livestock grazing has a limited effect on
      long-term vegetation productivity of semiarid rangelands, which is largely
      determined by rainfall. The communal lands in northeastern South Africa contain
      extensive degraded areas which have been mapped by the National Land Cover (NLC)
      program. Much evidence suggests that long-term heavy grazing is the cause of this
      degradation. In order to test for the prevalence of nonequilibrium dynamics, we
      determined the relative effects of rainfall- and grazing-induced degradation on
      vegetation productivity. The vegetation production in the NLC degraded areas was
      estimated using growth-season sums of the Normalized Difference Vegetation Index
      (sigmaNDVI), calculated using data from both the Advanced Very High Resolution
      Radiometer (AVHRR) (1985-2003) and Moderate-resolution Imaging Spectroradiometer
      (MODIS) (2000-2005). On average, rainfall and degradation accounted for 38% and
      20% of the AVHRR sigmaNDVI variance and 50% and 33% of the MODIS sigmaNDVI
      variance, respectively. Thus, degradation had a significant influence on long
      term vegetation productivity, and therefore the rangelands did not behave
      according to the nonequilibrium model, in which grazing is predicted to have a
      negligible long-term impact.

PMID- 17494400
TI  - Long-term patterns in tropical reforestation: plant community composition and
      aboveground biomass accumulation.
AB  - Primary tropical forests are renowned for their high biodiversity and carbon
      storage, and considerable research has documented both species and carbon losses
      with deforestation and agricultural land uses. Economic drivers are now leading
      to the abandonment of agricultural lands, and the area in secondary forests is
      increasing. We know little about how long it takes for these ecosystems to
      achieve the structural and compositional characteristics of primary forests. In
      this study, we examine changes in plant species composition and aboveground
      biomass during eight decades of tropical secondary succession in Puerto Rico, and
      compare these patterns with primary forests. Using a well-replicated
      chronosequence approach, we sampled primary forests and secondary forests
      established 10, 20, 30, 60, and 80 years ago on abandoned pastures. Tree species
      composition in all secondary forests was different from that of primary forests
      and could be divided into early (10-, 20-, and 30-year) vs. late (60- and 80
      year) successional phases. The highest rates of aboveground biomass accumulation
      occurred in the first 20 years, with rates of C sequestration peaking at 6.7 +/-
      0.5 Mg C x ha(-1) x yr(-1). Reforestation of pastures resulted in an accumulation
      of 125 Mg C/ha in aboveground standing live biomass over 80 years. The 80 year
      old secondary forests had greater biomass than the primary forests, due to the
      replacement of woody species by palms in the primary forests. Our results show
      that these new ecosystems have different species composition, but similar species
      richness, and significant potential for carbon sequestration, compared to remnant
      primary forests.

PMID- 17494401
TI  - Restoration of rivers used for timber floating: effects on riparian plant
      diversity.
AB  - Fluvial processes such as flooding and sediment deposition play a crucial role in
      structuring riparian plant communities. In rivers throughout the world, these
      processes have been altered by channelization and other anthropogenic stresses.
      Yet despite increasing awareness of the need to restore natural flow regimes for
      the preservation of riparian biodiversity, few studies have examined the effects
      of river restoration on riparian ecosystems. In this study, we examined the
      effects of restoration in the Ume River system, northern Sweden, where
      tributaries were channelized to facilitate timber floating in the 19th and early
      20th centuries. Restoration at these sites involved the use of heavy machinery to
      replace instream boulders and remove floatway structures that had previously
      lined stream banks and cut off secondary channels. We compared riparian plant
      communities along channelized stream reaches with those along reaches that had
      been restored 3-10 years prior to observation. Species richness and evenness were
      significantly increased at restored sites, as were floodplain inundation
      frequencies. These findings demonstrate how river restoration and associated
      changes in fluvial disturbance regimes can enhance riparian biodiversity. Given
      that riparian ecosystems tend to support a disproportionate share of regional
      species pools, these findings have potentially broad implications for
      biodiversity conservation at regional or landscape scales.

PMID- 17494402
TI  - Mature and old-growth riparian forests: structure, dynamics, and effects on
      Adirondack stream habitats.
AB  - Riparian forests regulate linkages between terrestrial and aquatic ecosystems,
      yet relationships among riparian forest development, stand structure, and stream
      habitats are poorly understood in many temperate deciduous forest systems. Our
      research has (1) described structural attributes associated with old-growth
      riparian forests and (2) assessed linkages between these characteristics and in
      stream habitat structure. The 19 study sites were located along predominantly
      first- and second-order streams in northern hardwood-conifer forests in the
      Adirondack Mountains of New York (U.S.A.). Sites were classified as mature forest
      (6 sites), mature with remnant old-growth trees (3 sites), and old-growth (10
      sites). Forest-structure attributes were measured over stream channels and at
      varying distances from each bank. In-stream habitat features such as large woody
      debris (LWD), pools, and boulders were measured in each stream reach. Forest
      structure was examined in relation to stand age using multivariate techniques,
      ANOVA, and linear regression. We investigated linkages between forest structure
      and stream characteristics using similar methods, preceded by information
      theoretic modeling (AIC). Old-growth riparian forest structure is more complex
      than that found in mature forests and exhibits significantly greater
      accumulations of aboveground tree biomass, both living and dead. In-stream LWD
      volumes were significantly (alpha = 0.05) greater at old-growth sites (200 m3/ha)
      compared to mature sites (34 m3/ha) and were strongly related to the basal area
      of adjacent forests. In-stream large-log densities correlated strongly with
      debris-dam densities. AIC models that included large-log density, debris-dam
      density, boulder density, and bankfull width had the most support for predicting
      pool density. There were higher proportions of LWD-formed pools relative to
      boulder-formed pools at old-growth sites as compared to mature sites. Old-growth
      riparian forests provide in-stream habitat features that have not been widely
      recognized in eastern North America, representing a potential benefit from late
      successional riparian forest management and conservation. Riparian management
      practices (including buffer delineation and restorative silvicultural approaches)
      that emphasize development and maintenance of late-successional characteristics
      are recommended where the associated in-stream effects are desired.

PMID- 17494403
TI  - Impacts of an exotic disease and vegetation change on foliar calcium cycling in
      Appalachian forests.
AB  - Because of the high calcium content of its foliage, Cornus florida (flowering
      dogwood) has been described as a calcium "pump" that draws calcium from deeper
      mineral soil and enriches surface soil horizons. However, over the last two
      decades an exotic fungal disease (dogwood anthracnose, Discula destructiva) has
      decimated populations of this once-common understory species. Its loss, combined
      with forest stand development, could alter intra-stand calcium cycling. We used
      data from long-term vegetation monitoring plots to examine the ecological role of
      C. florida in calcium cycling and to identify changes in annual foliar calcium
      cycling over a 20-year period between two sampling intervals, 1977-1979
      (preanthracnose) and 1995-2000 (post-anthracnose). Published equations were used
      to estimate foliar biomass per species for five forest types: alluvial, typic
      cove, acid cove, oak-hickory, and oak-pine. Calcium concentrations derived from
      foliage samples were used to estimate annual foliar calcium production per
      species for understory woody stems (<20 cm dbh) and total foliar calcium
      production for overstory stems (> or =20 cm dbh). At a given level of soil
      calcium availability, C. florida foliage contained greater concentrations of
      calcium than three other dominant understory species (Tsuga canadensis, Acer
      rubrum, and Rhododendron maximum). Between 1977-1979 and 1995-2000, the annual
      calcium contributions of understory woody vegetation declined across all forest
      types, ranging from 26% in oak-pine stands to 49% in acid coves. Loss of C.
      florida was responsible for only 13% of this decline in oak-pine stands, but
      accounted for 96% of the decline in typic coves. In oak-hickory and oak-pine
      stands, we observed large increases in the foliar biomass of T. canadensis, a
      species whose calcium-poor foliage increases soil acidity. Increases in overstory
      foliar biomass and calcium offset understory losses in three forest types
      (alluvial, typic coves, and oak-pine) but not in oak-hickory and acid cove
      stands. Overall, calcium cycling in oak-hickory stands was more negatively
      affected by the loss of C. florida than the other forest types. Oak-hickory
      forests comprise over a third of the total forest cover in the eastern United
      States, and decreases in annual calcium cycling could have cascading effects on
      forest biota.

PMID- 17494404
TI  - Impact of minimum winter temperatures on the population dynamics of Dendroctonus
      frontalis.
AB  - Predicting population dynamics is a fundamental problem in applied ecology.
      Temperature is a potential driver of short-term population dynamics, and
      temperature data are widely available, but we generally lack validated models to
      predict dynamics based upon temperatures. A generalized approach involves
      estimating the temperatures experienced by a population, characterizing the
      demographic consequences of physiological responses to temperature, and testing
      for predicted effects on abundance. We employed this approach to test whether
      minimum winter temperatures are a meaningful driver of pestilence from
      Dendroctonus frontalis (the southern pine beetle) across the southeastern United
      States. A distance-weighted interpolation model provided good, spatially
      explicit, predictions of minimum winter air temperatures (a putative driver of
      beetle survival). A Newtonian heat transfer model with empirical cooling
      constants indicated that beetles within host trees are buffered from the lowest
      air temperatures by approximately 1-4 degrees C (depending on tree diameter and
      duration of cold bout). The life stage structure of beetles in the most northerly
      outbreak in recent times (New Jersey) were dominated by prepupae, which were more
      cold tolerant (by >3 degrees C) than other life stages. Analyses of beetle
      abundance data from 1987 to 2005 showed that minimum winter air temperature only
      explained 1.5% of the variance in interannual growth rates of beetle populations,
      indicating that it is but a weak driver of population dynamics in the
      southeastern United States as a whole. However, average population growth rate
      matched theoretical predictions of a process-based model of winter mortality from
      low temperatures; apparently our knowledge of population effects from winter
      temperatures is satisfactory, and may help to predict dynamics of northern
      populations, even while adding little to population predictions in southern
      forests. Recent episodes of D. frontalis outbreaks in northern forests may have
      been allowed by a warming trend from 1960 to 2004 of 3.3 degrees C in minimum
      winter air temperatures in the southeastern United States. Studies that combine
      climatic analyses, physiological experiments, and spatially replicated time
      series of population abundance can improve population predictions, contribute to
      a synthesis of population and physiological ecology, and aid in assessing the
      ecological consequences of climatic trends.

PMID- 17494405
TI  - Spatial occurrence of a habitat-tracking saproxylic beetle inhabiting a managed
      forest landscape.
AB  - Because of the dynamic nature of many managed habitats, proper evaluation of
      conservation efforts calls for models that take into account both spatial and
      temporal habitat dynamics. We develop a metapopulation model for successional
      type systems, in which habitat quality changes over time in a predictable
      fashion. The occupancy and recruitment of the predatory saproxylic (dependent on
      dead wood) beetle Harminius undulatus was studied in a managed boreal forest
      landscape, covering 24,449 ha, in central Sweden. In a first step, we analyzed
      the beetle's occupancy pattern in relation to stand characteristics, and the
      amounts of present and past habitat in the surrounding landscape. Managed forest
      is suitable habitat when > or =60 years old, and immediately after cutting, but
      not between the ages of 10 and 60 years. The observed occupancy of H. undulatus
      was positively correlated with the stand's age as habitat. We used a
      metapopulation model to predict the current probability of occurrence in each
      forest stand, given the spatiotemporal distribution of suitable forest stands
      during the last 50 years. Metapopulation parameters were estimated by matching
      predicted spatial distributions with observed spatial distributions. The model
      predicted observed spatial distributions better than a similar model that assumed
      constant habitat quality of each forest stand. Thus, metapopulation models for
      successional-type systems, such as dead wood dependent organisms in managed
      forest landscapes, should include habitat dynamics. An estimated 82% of the
      landscape-wide recruitment took place in managed stands, which covered 87% of the
      forest area, in comparison with 18% in unmanaged stands, which covered 13% of the
      forest area. Among the managed stand types, > or =60-year-old stands and 3-7-year
      old clear-cuttings contributed to 79% of the total recruitment while 8-59-year
      old stands only contributed 3%. The results suggest the following guidelines to
      improve conditions for H. undulatus and other species with similar habitat
      requirements: (1) the proportion of the landscape constituted by younger stands
      should not be allowed to grow too large, (2) the rotation period of managed
      stands should not be allowed to be too short, and (3) dead wood should be
      retained and created at final cutting.

PMID- 17494406
TI  - Resource distributions among habitats determine solitary bee offspring production
      in a mosaic landscape.
AB  - Within mosaic landscapes, many organisms depend on attributes of the environment
      that operate over scales ranging from a single habitat patch to the entire
      landscape. One such attribute is resource distribution. Organisms' reliance on
      resources from within a local patch vs. those found among habitats throughout the
      landscape will depend on local habitat quality, patch quality, and landscape
      composition. The ability of individuals to move among complementary habitat types
      to obtain various resources may be a critical mechanism underlying the dynamics
      of animal populations and ultimately the level of biodiversity at different
      spatial scales. We examined the effects that local habitat type and landscape
      composition had on offspring production and survival of the solitary bee Osmia
      lignaria in an agri-natural landscape in California (U.S.A.). Female bees were
      placed on farms that did not use pesticides (organic farms), on farms that did
      use pesticides (conventional farms), or in seminatural riparian habitats. We
      identified pollens collected by bees nesting in different habitat types and
      matched these to pollens of flowering plants from throughout the landscape. These
      data enabled us to determine the importance of different plant species and
      habitat types in providing food for offspring, and how this importance changed
      with landscape and local nesting-site characteristics. We found that increasing
      isolation from natural habitat significantly decreased offspring production and
      survival for bees nesting at conventional farms, had weaker effects on bees in
      patches of seminatural habitat, and had little impact on those at organic farm
      sites. Pollen sampled from nests showed that females nesting in both farm and
      seminatural habitats relied on pollen from principally native plant species
      growing in seminatural habitat. Thus connectivity among habitats was critical for
      offspring production. Females nesting on organic farms were buffered to isolation
      effects by switching to floral resources growing at the farm site when
      seminatural areas were too distant. Overall local habitat conditions (farm
      management practices) can help bolster pollinators, but maintaining functional
      connectivity among habitats will likely be critical for persistence of pollinator
      populations as natural habitats are increasingly fragmented by human activities.

PMID- 17494407
TI  - Abiotic constraints eclipse biotic resistance in determining invasibility along
      experimental vernal pool gradients.
AB  - Effective management of invasive species requires that we understand the
      mechanisms determining community invasibility. Successful invaders must tolerate
      abiotic conditions and overcome resistance from native species in invaded
      habitats. Biotic resistance to invasions may reflect the diversity, abundance, or
      identity of species in a community. Few studies, however, have examined the
      relative importance of abiotic and biotic factors determining community
      invasibility. In a greenhouse experiment, we simulated the abiotic and biotic
      gradients typically found in vernal pools to better understand their impacts on
      invasibility. Specifically, we invaded plant communities differing in richness,
      identity, and abundance of native plants (the "plant neighborhood") and depth of
      inundation to measure their effects on growth, reproduction, and survival of five
      exotic plant species. Inundation reduced growth, reproduction, and survival of
      the five exotic species more than did plant neighborhood. Inundation reduced
      survival of three species and growth and reproduction of all five species.
      Neighboring plants reduced growth and reproduction of three species but generally
      did not affect survival. Brassica rapa, Centaurea solstitialis, and Vicia villosa
      all suffered high mortality due to inundation but were generally unaffected by
      neighboring plants. In contrast, Hordeum marinum and Lolium multiflorum, whose
      survival was unaffected by inundation, were more impacted by neighboring plants.
      However, the four measures describing plant neighborhood differed in their
      effects. Neighbor abundance impacted growth and reproduction more than did
      neighbor richness or identity, with growth and reproduction generally decreasing
      with increasing density and mass of neighbors. Collectively, these results
      suggest that abiotic constraints play the dominant role in determining
      invasibility along vernal pool and similar gradients. By reducing survival,
      abiotic constraints allow only species with the appropriate morphological and
      physiological traits to invade. In contrast, biotic resistance reduces
      invasibility only in more benign environments and is best predicted by the
      abundance, rather than diversity, of neighbors. These results suggest that
      stressful environments are not likely to be invaded by most exotic species.
      However, species, such as H. marinum, that are able to invade these habitats
      require careful management, especially since these environments often harbor rare
      species and communities.

PMID- 17494408
TI  - Fragmention by agriculture influences reproductive success of birds in a
      shrubsteppe landscape.
AB  - Shrubsteppe communities are among the most imperiled ecosystems in North America
      as a result of conversion to agriculture and other anthropogenic changes. In the
      Intermountain West of the United States, these communities support a unique
      avifauna, including several species that are declining and numerous others that
      are of conservation concern. Extensive research in the eastern and central United
      States and in Scandinavia suggests that fragmentation of formerly continuous
      forests and grasslands adversely affects reproductive success of birds, yet
      little is known of the potential effects on avian communities in Western
      shrublands. I used multi-model inference to evaluate the potential effects of
      local and landscape variables on nest predation and brood parasitism, and
      behavioral observations of color-banded birds to evaluate the potential effects
      of habitat fragmentation on seasonal reproductive success of passerines in the
      shrubsteppe of eastern Washington State, USA. Reproductive success of shrubsteppe
      obligate passerines was lower in landscapes fragmented by agriculture than in
      continuous shrubsteppe landscapes. Daily survival rates for nests of Brewer's
      Sparrows (Spizella breweri; n=496) and Sage Thrashers (Oreoscoptes montanus;
      n=128) were lower in fragmented landscapes, and seasonal reproductive success
      (percentage of pairs fledging young) of Sage Sparrows (Amphispiza belli; n=146)
      and Brewer's Sparrows (n=59) was lower in fragmented landscapes. Rates of
      parasitism by Brown-headed Cowbirds (Molothrus ater) overall were low (4%) but
      were significantly greater in fragmented landscapes for Brewer's Sparrows, and
      parasitism resulted in fewer young fledged from successful nests. Simple models
      of population growth using landscape-specific fecundity and estimates of adult
      survival derived from return rates of banded male Sage Sparrows and Brewer's
      Sparrows suggest that fragmented shrubsteppe in Washington may be acting as a
      population sink for some species. Immediate conservation needs include halting
      further fragmentation of shrubsteppe, restoring low-productivity agricultural
      lands and annual grasslands to shrubsteppe where possible, and convincing the
      public of the intrinsic value of these imperiled ecosystems.

PMID- 17494409
TI  - Factors affecting aural detections of songbirds.
AB  - Many factors affect the number of birds detected on point count surveys of
      breeding songbirds. The magnitude and importance of these factors are not well
      understood. We used a bird song simulation system to quantify the effects of
      detection distance, singing rate, species differences, and observer differences
      on detection probabilities of birds detected by ear. We simulated 40 point counts
      consisting of 10 birds per count for five primary species (Black-and-white
      Warbler Mniotilta varia, Black-throated Blue Warbler Dendroica caerulescens,
      Black-throated Green Warbler Dendroica virens, Hooded Warbler Wilsonia citrina,
      and Ovenbird Seiurus aurocapillus) over a range of 15 distances (34-143 m). Songs
      were played at low (two songs per count) and high (13-21 songs per count) singing
      rates. Detection probabilities averaged across observers ranged from 0.60 (Black
      and-white Warbler) to 0.83 (Hooded Warbler) at the high singing rate and 0.41
      (Black-and-white Warbler) to 0.67 (Hooded Warbler) at the low singing rate.
      Logistic regression analyses indicated that species, singing rate, distance, and
      observer were all significant factors affecting detection probabilities. Singing
      rate x species and singing rate X distance interactions were also significant.
      Simulations of expected counts, based on the best logistic model, indicated that
      observers detected between 19% (for the worst observer, lowest singing rate, and
      least detectable species) and 65% (for the best observer, highest singing rate,
      and most detectable species) of the true population. Detection probabilities on
      actual point count surveys are likely to vary even more because many sources of
      variability were controlled in our experiments. These findings strongly support
      the importance of adjusting measures of avian diversity or abundance from
      auditory point counts with direct estimates of detection probability.

PMID- 17494410
TI  - [Pre-psychotic states--contemporary diagnostic and therapeutic issues. Part I.
      Clinical identification of pre-psychotic states].
AB  - Early intervention in psychotic disorders, particularly schizophrenia, has been
      increasingly recognized as important by clinicians. The benefits of early
      intervention in schizophrenia to patients include prevention of neurobiological
      changes, minimization of secondary morbidity and prevention of relapse. Other
      benefits of prepsychotic intervention include the capacity to research the onset
      phase of psychosis. We would like to support in our paper a statement by Maeres:
      What is needed is not diagnosing the early stages of schizophrenia but the
      diagnosis of prepsychotic schizophrenia. We are interested in recognizing the
      schizophrenia 'prodrome' prospectively using to concepts: subjects 'at risk
      mental state' (ARMS) and subjects from 'ultra high risk' (UHR) group. For
      clinical reasons that involves both some clinical features of pre-psychotic
      states (attenuated psychotic symptoms) and some "trait factors", i.e. schizotypal
      personality or family predisposition factors. Recent data revealed that some
      characteristics of pre-psychotic states had stronger predictive value: longer
      symptoms duration, lower level of GAF (< 40), and presence of attenuated
      psychotic symptoms. The possibility of providing intervention prior to the onset
      of psychosis has risen from recent interest in early intervention in these pre
      psychotic states.

PMID- 17494411
TI  - [Pre-psychotic states--contemporary diagnostic and therapeutic issues. Part II.
      The biological markers of the risk of schizophrenia. Therapy of pre-psychotic
      states].
AB  - The authors review the literature on the topic of early identification and
      intervention in "pre-psychotic" and "pre-schizophrenic" persons. Most of the
      early intervention programmes include more or less "false positive results".
      There is still no classic biological marker of schizophrenia available. Authors
      review the possible markers of schizophrenia, including some neurophysiological
      and neurocognitive disorders (eye-tracking dysfunction, sensory motor gating
      dysfunction, working memory and other neurocognitive dysfunctions) and also
      structural, neurochemical and functional brain abnormalities. Unfortunately, the
      marker of transition to psychosis is still unknown. Only the complex analysis of
      all possible factors: family, social, clinical and biological can be helpful in
      identification of the future schizophrenic persons. The authors also review the
      research on the treatment of "pre-psychotic" persons. The most frequent methods
      used in these cases are the generation antipsychotics in low doses and
      psychotherapy. The results are promising, but need further confirmation, both in
      every day practice and in randomized controlled trials.

PMID- 17494412
TI  - [Functioning and occupational activity of persons with mental disorders--research
      review].
AB  - Occupational functioning of persons with mental disorders is a serious, rarely
      discussed problem in Polish literature. Foreign research review shows that
      occupational activity of persons with mental disorders seriously affects their
      mental functioning. It was suggested that the major way of mental health
      promotion was re-employment. However the risk of mental disorders (especially
      affective and anxiety disorders) increased with loss of some work. Despite of a
      healthy influence of occupational activity on the mental health among people
      suffering from mental disorders, the high level of unemployment in that group
      (higher than among people with somatic diseases) is observed. The aim of this
      article is to describe the problem of occupational activity of persons with
      mental disorders, as well as in comparison to people without mental disorders and
      those with somatic diseases. The relationship between mental disorders and
      occupational activity is shown. Psychological benefits of occupational
      functioning as well as difficulties at work caused by mental disorders are
      explained. The costs connected with mental disorders are described.

PMID- 17494413
TI  - [The social functioning of individuals with various psychiatric disorders].
AB  - AIM: The aim of the study was to compare the social functioning of individuals
      with various psychiatric disorders, as well as finding factors associated with
      the level of social functioning. METHOD: Patients (n = 969) from the F2, F3, F4,
      F5 and F6 diagnostic groups (according to ICD-10) were assessed after admission
      into one of several European hospitals (observation I), as well as 3 months after
      discharge (observation II). The Client Sociodemographic and Clinical History
      Inventory, Brief Psychiatric Rating Scale, v 4.0 and Groningen Social Disability
      Schedule were used in the study. RESULTS: Analysis of partial correlations taking
      age into account indicated a significant association of the level of social
      functioning with diagnosis, city, as well as the professional status of a patient
      and his/her marital status. Taking into account the severity of a condition, the
      diagnostic group was not associated with the level of social functioning. No
      association was found between social disability and either sex, education, the
      number of episodes, psychiatric hospitalisation or duration of the disorder.
      CONCLUSIONS: Both during an acute episode and after hospital treatment, patients
      with personality, eating or schizophrenic disorders functioned less effectively
      than those having affective or anxiety disorders. The severity of a condition was
      significantly associated with the level of disability, regardless of the
      diagnostic group. Married and professionally active patients functioned
      significantly better.

PMID- 17494414
TI  - [Social competencies of persons with a dual diagnosis--literature review].
AB  - Therapy and rehabilitation of mentally ill persons abusing alcohol and other
      psychoactive substances have recently become a growing problem. Rehabilitation of
      these patients is particularly difficult because of the number of deficits
      accompanying schizophrenia. These deficits make traditional methods of substance
      dependence treatment impossible to apply in the case of mentally ill persons. The
      article presents results of the studies on cognitive deficits and limited social
      competencies of persons suffering from schizophrenia and dependent on alcohol and
      other psychoactive substances. We also present two treatment programmes which
      involve improvement of social competencies.

PMID- 17494415
TI  - [Is there a correlation between duration of hospitalization and SCAN diagnosis?].
AB  - AIM: The authors have made an effort to find the answer to the question what are
      the reasons for long hospitalizations in stationary wards and in the day hospital
      of the Wroclaw Mental Health Care Centre? In order to achieve this goal the
      correlation of the SCAN questionnaire diagnoses and length of stay in the
      aforementioned settings was analyzed. METHODS: Analysis included 220 patients
      treated in the Wroclaw Mental Health Care Centre of which 111 patients were
      placed in day hospital and 109 in stationary wards. The correlation of length of
      stay in day hospital and in stationary wards with number of SCAN diagnoses in ICD
      10 diagnostic groups was investigated. RESULTS: Duration of hospitalization was
      relatively long for both day hospital patients (150 days) and stationary ward
      patients (58 days). Contrary to expectations there was no correlation between the
      number of SCAN diagnoses and length of stay in the hospital. Patients who were
      diagnosed using SCAN as having affective disorders and anxiety disorder stayed in
      the hospital shorter despite the fact they had more comorbid disorders than
      patients diagnosed using SCAN as having psychotic disorders both in day hospital
      and in stationary wards. CONCLUSIONS: Examination using the SCAN questionnaire
      cannot be used as prognosis of the length of stay either in day hospital or in
      stationary wards. Duration of hospitalization depends mainly on the diagnostic
      category (anxiety and affective disorders are associated with shorter hospital
      stays than psychotic disorders) irrespective of the number of diagnoses a patient
      received. It also depends on local therapeutic traditions and preferences
      (dominance of long-term care and the rehabilitation model of treatment instead of
      active acute intervention aiming at quick discharge from the hospital).

PMID- 17494416
TI  - [The psychometric properties of the Proverb-Metaphor Test].
AB  - Abstract thinking belongs to intellectual abilities of the highest level of the
      evolutionary development, thanks to which operations such a classification,
      systematisation and comparison are possible. AIM: An analysis of the psychometric
      properties of the Proverb-Metaphor Test (TPM) which has been used in the German
      speaking countries since 2001. The TPM was subject to the process of translation-
      retranslation--travesty in order to be adapted to clinical conditions in Poland.
      MATERIAL: 60 patients of the Department of Psychiatry, Medical University of
      Lublin with diagnosed paranoid schizophrenia (according to ICD-10 criteria).
      METHODS: PANSS and TPM was carried out amongst 15 patients at the beginning of
      the hospitalisation (the first stage of the research) and among all persons
      during the remission of syndromes (the second stage). The WAIS-R (PL) was used in
      the second stage. RESULTS AND CONCLUSION: 1. The TPM is a reliable instrument, of
      high criteria propriety. 2. The evaluated test is a relatively homogeneous
      research tool. 3. The TPM is, thanks to its simple construction and the short
      carrying out time, a practical method of abstract thinking evaluation. 4. The TPM
      may be a useful instrument enabling long term prognosis.

PMID- 17494417
TI  - [Psychiatric aspects of the irritable bowel syndrome].
AB  - Irritable bowel syndrome is one of the most frequent diseases of the
      gastrointestinal tract. Doctors working in different fields deal with this
      problem in their everyday practice. The frequency of this disorder is 10-20% in
      the adult population and it is a frequent cause of work absence. Thus, it is not
      only a general medical problem but also a social one. This syndrome is one of the
      most typical examples of psychosomatic disorders--somatic disorders conditioned
      or worsened by psychosocial factors. The process of disturbance development in
      this syndrome is complex and in most cases, to some degree, associated with
      depressive symptoms. It may be a result of conversion of anxiety into somatic
      symptoms. It is frequently a result of the so-called dissociative conversion--a
      transformation (conversion) of persistent anxiety symptoms into secondary somatic
      disturbances. The authors suggest two possible mechanisms connecting irritable
      bowel syndrome and depression. They also distinguish in a novel way several types
      of this syndrome basing on the accompanying psychopathological symptoms. The
      paper also suggests possible therapeutic approaches in all the presented subtypes
      of irritable bowel syndrome.

PMID- 17494419
TI  - [Co-occurrence of psychiatric and dermatologic disorders. Case studies].
AB  - Cytokine regulation disturbances have a significant role in the pathogenesis of
      psychiatric disorders, schizophrenia and depression, as well as in dermatologic
      disorders. Probably it is one of the reasons of the co-occurrence of these two
      kinds of disorders. Two cases of psychiatric and dermatologic disorders occurring
      together are presented in this paper. In the first case study depression was
      associated with atopic dermatitis, in the second case the delusion disorder was
      described with secondary dermatologic sequellae. In both cases, after
      psychopharmacotherapy, the improvement of the psychic state was correlated with
      the relief or regression of skin symptoms.

PMID- 17494418
TI  - [Age and attitudes in relation to eating in girls with eating disorders and
      healthy girls].
AB  - AIM: The aim of the study was to compare of the D.M. Garner, M.P. Olmsted and J.
      Polivy Eating Disorders Inventory (EDI) results obtained by healthy lower
      secondary, secondary and college students versus the results obtained with their
      peers with eating disorders. METHOD: The examined group consisted of 379 girls
      attending Lublin lower secondary schools (123 persons), secondary schools (50
      persons) and college students (206 persons) as well as 90 girls undergoing
      medical treatment due to eating disorders (30 lower secondary school students and
      30 college students). All these persons were administered the D.M. Garner, M.P.
      Olmsted and J. Polivy Eating Disorders Inventory (EDI). RESULTS: The tests
      conducted revealed significant statistical differences between the Eating
      Disorders Inventory (EDI) results obtained by secondary school students and
      college students with eating disorders and those obtained by their healthy peers
      as well as the lack of significant differences between healthy and ill lower
      secondary school students. CONCLUSIONS: 1. Age is a significant factor related to
      eating disorders. 2. As regards their attitude in relation to eating and their
      own body, healthy lower secondary school students are not much different from
      their peers diagnosed with eating disorders. 3. Incorrect attitudes in relation
      to eating and their own body in girls with eating disorders increase in a
      significant way at secondary school and at college periods.

PMID- 17494420
TI  - [The influence of acute limphoblastic leukaemia and its treatment on the
      patient's mental functioning--a literature review].
AB  - The aim of the literature review was the problem of psychiatric complications of
      intensive chemo- and radiotherapy, which were used in childhood. These days most
      children who suffer from acute leukaemia are successfully treated. Most studies
      indicate cognitive dysfunctions, anxiety and mood disorders. These days a new
      scheme of chemo- and radiotherapy should be introduced, which should consider the
      mental state of the patients.

PMID- 17494421
TI  - [The outcome of inpatient psychotherapy and previous psychotherapy duration].
AB  - AIM: The previous psychotherapy duration was the main independent variable.
      METHOD: 301 patients successively reporting for inpatient treatment in the Clinic
      of Neurotic Disorders received questionnaires. 274 patients completed the
      treatment and returned all the tests and were divided into three groups: a) those
      without previous psychotherapy, b) those with the experience of previous short
      term therapy, c) those with previous long-term psychotherapy. The following tools
      were used: Hopkins Symptom Checklist, Sense of Coherence, Questionnaire of
      Motivation, and Adjective Check List. RESULT: Previous psychotherapy duration
      discriminates symptoms, coherence, motivational factors, personality aspects,
      both in the beginning of psychotherapy and at the time of discharge from the
      hospital.

PMID- 17494422
TI  - ["Incontinence need not be a permanent condition"].

PMID- 17494423
TI  - ["Fit for 100" model project--exercise classes for the oldest old: promoting
      muscle strength and maintaining routine competence].

PMID- 17494424
TI  - [Peripheral vestibular diseases--the salutary perspective: from symptom
      management to health promoting nursing care].

PMID- 17494425
TI  - [Problems from general practice--solutions for general practice: hand cleanliness
      -a never ending story].

PMID- 17494426
TI  - [New bandage system for venous compression in general practice study: better
      patient compliance supports wound healing].

PMID- 17494427
TI  - [Protecting nursing home residents].

PMID- 17494428
TI  - [Physical restraints in geriatric care: attitudes of nurses, patients and their
      families].
AB  - Nurses' attitudes influence decisions on physical restraints. A literature
      analysis was conducted on nurses', patients', and their families' attitudes
      towards physical restraint use in the elderly. While nurses' attitudes are
      characterized by ambivalence, patients and their relatives express mainly
      negative feelings towards the use of physical restraints. Knowledge about
      nurses', patients', and their relatives' attitudes is indispensable for the
      development of alternative interventions. Patients' dignity as well as their
      right to freedom and movement must be respected and protected.

PMID- 17494429
TI  - [Nursing care and services for people with Parkinson's disease in nursing homes.
      An explorative review].
AB  - Actual demographic developments and the incurability of Parkinson's disease force
      the care for the elderly to establish specialised concepts and methods for
      residents who suffer from this disease. Based on an explorative literature review
      the current empirical knowledge concerning the care for persons with Parkinson's
      disease has been compiled. Overall it became visible that topics like care for
      patients with Parkinson's disease have been increasingly considered in scientific
      literature during the recent years, but there is still a lack of scientific
      studies which focus on the field of care for the elderly.

PMID- 17494430
TI  - [Staff development in geriatric nursing. Occupational continuing education
      benefits everyone].

PMID- 17494431
TI  - [Nurse counseling as a component of professional job description: making quality
      noticeable].

PMID- 17494432
TI  - [Coerced treatment according to the right to treatment regulation: never contrary
      to the will of mentally competent patients].

PMID- 17494433
TI  - [Human images in nursing--1: Christianity: God's creation and likeness].

PMID- 17494434
TI  - [From case to case: how one makes the bed...].

PMID- 17494435
TI  - [Recognizing and understanding illnesses: movement impairment].

PMID- 17494436
TI  - Welsh nurses stand to gain from national elections.

PMID- 17494437
TI  - A black and white issue. Interview by Carol Davis.
AB  - Itai Nyamatore is promoting equality for service users in Britain, based on her
      experiences of nursing in Zimbabwe.

PMID- 17494438
TI  - Slavery: here and now. Interview by Alison Moore and Bill Doult.
AB  - Although British slavery was outlawed 200 years ago, many forms of slavery
      persist across the world. And there are resulting health problems.

PMID- 17494439
TI  - Behind the wire. Interview by Mike Hayward.
AB  - Providing health care to immigration detainees, possibly facing deportation, is
      complex and challenging. The culturally diverse population has many demands.

PMID- 17494440
TI  - Back on track.
AB  - Some NHS trusts offer access to a life coach through their occupational health
      programmes.

PMID- 17494441
TI  - Outing anal cancer.

PMID- 17494442
TI  - Nursing students' practice in providing oral hygiene for patients.
AB  - AIM: To explore and identify precedent factors that may influence nursing
      students' oral hygiene practice in hospitalised patients, by using an adaptation
      of the Precede Model. METHOD: A quantitative approach with a descriptive design
      was adopted in this pilot study. A questionnaire was designed and implemented as
      a self-report method of data collection. A convenience sample of 37 second-year
      diploma nursing students in an Irish teaching hospital participated in the study.
      RESULTS: The clinical area and the practices within it are influential factors in
      the provision of oral hygiene. Students are exposed to and influenced by outdated
      and non-research-based practices. Role modelling is an effective means of
      motivating and reinforcing student practices. However, qualified nurses'
      practices need to be critically reviewed before assuming that they can act as
      role models in assisting students to implement research-based oral hygiene.
      CONCLUSION: Formal education, current practices, socialisation and role modelling
      may influence students' behaviour in relation to oral hygiene. The results should
      be tentatively reviewed by clinical staff as an indication of current practices.

PMID- 17494443
TI  - Factors that influence aggressive behaviour in acute care settings.
AB  - Patients with critical illness or severe trauma may feel fear, anxiety and
      powerlessness, which can lead to aggressive behaviour. This article examines
      factors that contribute to patient aggression in acute care areas and identifies
      how these incidents can be minimised.

PMID- 17494444
TI  - Ethical aspects of withdrawing and withholding treatment.
AB  - Decisions about withdrawing and withholding treatment are common in health care.
      During almost every encounter between health professionals and patients a
      decision needs to be made about treatment options. In most cases these choices do
      not pose any difficulty, for example, starting antibiotics when a patient has an
      infection. However, decisions not to treat, or to stop treating, raise
      fundamental questions about the nature and purpose of nursing and the ethics of
      end-of-life care. This article argues that nurses need to be proactive in
      deciding what is nursing care and what is treatment. An ethical distinction is
      drawn between acts and omissions. How this distinction relates to withdrawing and
      withholding treatment will be considered. Further ethical issues discussed relate
      to judgements about the futility of treatment, patient autonomy and nurses' duty
      of care to patients at the end of life.

PMID- 17494445
TI  - Prevention of hepatitis B in travellers: pre-travel consultation.
AB  - Foreign travel is increasing and many travellers are at risk of developing
      hepatitis B. This article examines the epidemiology, diagnosis and prevention of
      this disease to enable health professionals to offer appropriate support and
      advice to travellers at pre-travel consultations.

PMID- 17494446
TI  - Person-centred care.

PMID- 17494447
TI  - Learn to play hardball.

PMID- 17494448
TI  - Shipshape to nurse.

PMID- 17494449
TI  - Closed doors.

PMID- 17494450
TI  - Dietary and holistic treatment of recurrent calcium oxalate kidney stones: review
      of literature to guide patient education.
AB  - Urolithiasis is a condition that can cause significant morbidity among patients.
      Dietary manipulations traditionally advised include fluid, protein, oxalate,
      calcium, citrate, and sodium changes in the diet. Evidence-based practice
      guidelines suggest that there is not ample evidence to confidently recommend
      dietary changes, since inadequate studies have been done to quantify the risks of
      diet in stone formation. While fluid intake patterns have the weightiest evidence
      in the literature, not even fluid intake meets the guidelines for evidence-based
      practice. Health care providers should recognize that current patient education
      is largely based on intuition. It behooves us as clinicians to look critically at
      all our practices, review the available literature, and question what we believe
      we know. A summary of available literature is provided to guide the clinician in
      educating patients in reducing their risk of recurrent calcium oxalate stone
      disease.

PMID- 17494451
TI  - Group session teaching of behavioral modification program for urinary
      incontinence: establishing the teachers.
AB  - In a past study it was determined that a nurse scientist and an urologist were
      able to prevent incontinence in women through teaching strategies in a group
      setting. This study determined that the same knowledge could be taught by an
      experienced nurse practitioner and an experienced urology nurse.

PMID- 17494452
TI  - Demystifying leak point pressures: the valuable tool for functional assessment.
AB  - Leak point pressures have evolved over the last several years as tools for
      functional bladder assessment. Often, the term leak point pressure is used when
      referring to abdominal leak point pressures (ALPP). In fact, there are two leak
      point pressure measurements in urodynamics, ALPP and detrusor or bladder leak
      point pressures (DLPP). Defining these two leak point pressures and understanding
      their very different intrinsic values are important goals for the urodynamicist.

PMID- 17494453
TI  - Evidence-based practice for evaluation and management of female urinary tract
      infection.
AB  - Treatment and management of uncomplicated, lower urinary tract infections in
      adult females is unique in comparison to other patient populations. In this
      article, best practices and evidence-based research for treating a urinary tract
      infection in this group of patients are examined. A typical case of a female
      client in an outpatient urology setting is compared to recommendations in the
      literature. Interventions in the scenario are examined against available
      guidelines, revealing that some practices are supported, others are
      contraindicated, and gaps are identified.

PMID- 17494454
TI  - Laparoscopic radical robotic prostatectomy: a case study.
AB  - The management of prostate cancer includes observation, hormonal therapy, radical
      prostate surgery (open, laparoscopic, or laparoscopic robotic), external beam
      radiation, brachytherapy, or cryotherapy. Laparoscopic radical robotic
      prostatectomy is the newest technology in minimally invasive surgery. This is a
      case study of a patient who chose to undergo laparoscopic robotic prostatectomy
      for his prostate cancer.

PMID- 17494455
TI  - National Pressure Ulcer Advisory Panel's updated pressure ulcer staging system.
AB  - The National Pressure Ulcer Advisory Panel has updated the definition of a
      pressure ulcer and the stages of pressure ulcers based on current research and
      expert opinion solicited from hundreds of clinicians, educators, and researchers
      across the country. The amount of anatomical tissue loss described with each
      stage has not changed. New definitions were drafted to achieve accuracy, clarity,
      succinctness, clinical utility, and discrimination between and among the
      definitions of other pressure ulcer stages and other types of wounds. Deep tissue
      injury was also added as a distinct pressure ulcer in this updated system.

PMID- 17494456
TI  - Adding to the evidence base--a critique of 'group session teaching of behavioral
      modification program for urinary incontinence: establishing the teachers'.

PMID- 17494457
TI  - The new vaccine to prevent HPV.

PMID- 17494458
TI  - Update on vaccination against pertussis.
AB  - Despite the effectiveness of vaccination programs in the United States, pertussis
      continues to occur among all age groups. Vaccination continues to be the most
      effective strategy for preventing pertussis. Prevention efforts should aim at
      maintaining high childhood vaccination rates and promoting adolescent and adult
      vaccination programs.

PMID- 17494459
TI  - Getting ready for certification: general male genital disorders.

PMID- 17494460
TI  - Native Americans: traditional healing.
AB  - There are an estimated 4.1 million people who are classified as American Indian
      and Alaska Native alone or in combination with one or more other races. This
      racial group composes 1.5% of the total U.S. population. The leading causes of
      illness and death among American Indians are heart disease, cancer, unintentional
      injuries (accidents), diabetes, and stroke. American Indians also have a high
      prevalence of obesity, chronic renal failure, alcoholism, and are at increased
      risk for mental health issues and suicide. In an effort to build a trusted
      relationship with these patients and become an active participant in their care,
      the health care provider must demonstrate respect for the traditions of the
      American Indian.

PMID- 17494461
TI  - Cholesterol, cholesterol-lowering agents/statins, and urologic disease: Part V-
      Statins versus aspirin for primary prevention, and the winner is...?
AB  - There are no national guidelines when comparing an aspirin daily to a statin drug
      in individuals with no history of a cardiovascular event (primary prevention).
      However, recent reviews of the medical clinical research on statins and aspirin
      for preventing a first coronary heart disease (CHD) event concluded that compared
      to no treatment, aspirin is cheaper and has more of an impact in middle-aged men
      whose 10-year risk for CHD is 7.5% or higher, and adding a statin to aspirin
      therapy is better in terms of cost effectiveness when a patient's 10-year CHD
      risk before any treatment is greater than 10%. However, when scrutinizing these
      data it seems that statins beat aspirin in every single risk-reduction category,
      and has equal to perhaps less side effects, but a statin costs more. In addition,
      patients should be informed about the recent observational data suggesting that
      statins may reduce mortality from other causes such as prostate cancer.

PMID- 17494462
TI  - Cholesterol, cholesterol-lowering agents/statins, and urologic disease: Part VI-
      The recent rise and fall of the HDL-boosting drug torceptrapib.
AB  - Pfizer Inc. recently discontinued its billion-dollar investment and phase III
      clinical trial of their new high-density lipoprotein (HDL) or "good cholesterol"
      boosting drug torceptrapib because of unexpected life-threatening side effects.
      To provide an objective discussion with patients looking for the next miracle
      drug or even dietary supplement in medicine, it is important to provide an
      overview of the history of this drug. It should serve as an important lesson that
      traditional lifestyle factors and proven heart healthy medications have stood the
      test of time in terms of research. Despite the current interest in drug
      development, traditional HDL-boosting lifestyle initiatives such as exercise,
      weight loss, and smoking cessation can be incorporated now and are heart and
      urologic healthy.

PMID- 17494463
TI  - Ethnographic research.

PMID- 17494464
TI  - Nursing relationships in ethnographic research: what of rapport?
AB  - Julie McGarry examines some of the issues associated with relationships that
      develop in ethnographic research. In particular, she considers questions that
      arise from the notion of 'rapport' between researcher and participant--questions
      that the literature has generally tended to avoid.

PMID- 17494465
TI  - Ethnography and staying in your own nest.
AB  - In a 2004 paper, Martin Johnson suggested that 'too many of us study our own
      students for reasons that can only be explained by excessive convenience'. Here,
      Deborah Roberts argues that studying a group of students known to the researcher
      is anything but convenient. Rather, it requires careful consideration and skill.
      She makes a case for more researchers to study their own students.

PMID- 17494466
TI  - Through the looking glass: being a critical ethnographic researcher in a familiar
      nursing context.
AB  - This article draws on the primary author's experiences of conducting a critical
      ethnographic study within the emergency department where she works. Extracts from
      her journal entries illustrate the tensions that emerged. These are theorised and
      discussed, resulting in a 'troubling' of the ethnographic field.

PMID- 17494467
TI  - Ethical considerations in phenomenological research.
AB  - Wendy Walker examines some important ethical issues that researchers need to
      consider before and during phenomenological research. She argues that failure to
      address such issues means putting at risk the rights of research participants.

PMID- 17494468
TI  - Lost in translation? Undertaking transcultural qualitative research.
AB  - If nurses are to undertake rigorous transcultural research, they must take
      account of the cultural and linguistic diversity of the countries in which they
      propose to complete their work. Fiona Elizabeth Irvine and colleagues describe
      the experiences of researchers undertaking the qualitative phase of a study of
      Japanese and UK nurse educators, and consider the measures that can be taken to
      enhance the rigour of transcultural research.

PMID- 17494469
TI  - Getting started with qualitative research: developing a research proposal.
AB  - The aim of this article is to illustrate in detail important issues that research
      beginners may have to deal with during the design of a qualitative research
      proposal in nursing and health care. Cristina Vivar has developed a 17-step
      process to describe the development of a qualitative research project. This
      process can serve as an easy way to start research and to ensure a comprehensive
      and thorough proposal.

PMID- 17494470
TI  - 'You could have been a doctor'.
AB  - Laura Serrant-Green talks about why she decided to be a nurse, her work in
      research, what she has learned during her career, as well as the women who have
      helped her along the way as she prepares to embark on her third year as editor of
      Nurse Researcher.

PMID- 17494471
TI  - Model empathy and respect when immunizing children who fear needles.

PMID- 17494474
TI  - Cancer changed Donalda MacDonald's perspective on life--and how she teaches.
      Interview by Tara Tosh-Kennedy.

PMID- 17494475
TI  - Educating for tomorrow: enhancing nurses' pain management knowledge.
AB  - The Centre for Education and Research on Aging and Health at Lakehead University,
      Thunder Bay, Ontario, was the lead agency in developing a pain management
      continuing education program for front-line nurses in a variety of settings in
      northwestern Ontario. A committee of experts from the centre as well as from the
      Thunder Bay Regional Health Sciences Centre; Regional Cancer Care; the Pain and
      Symptom Management Team, North West Community Care Access Centre; the Victorian
      Order of Nurses and Lakehead University school of nursing developed the program.
      The program included a pre-test of knowledge and attitudes; four two-hour
      educational sessions focusing on total pain, acute pain, chronic pain and cancer
      pain; and a post self-test at the end of each session. The educational sessions
      were evaluated through a survey to participants. Overall, the nurses expressed
      high satisfaction with the workshops, and the post self-tests indicated a better
      understanding of patients' pain management experiences. As a result of the
      evaluation, the education planning committee refined the program, which is
      currently being delivered to nurses in rural and remote communities via
      telehealth.

PMID- 17494476
TI  - Enduring values in changing times: the CNA Codes of Ethics.

PMID- 17494477
TI  - Reaching milestones in regulation.

PMID- 17494478
TI  - What patients want: A content analysis of key qualities that influence patient
      satisfaction.
AB  - We sought to identify key qualities of healthcare that influence patient
      appraisal of satisfaction with primary care. An Internet survey of patients was
      used to collect anonymous ratings of physicians on several dimensions of
      healthcare experiences, as well as comments about aspects of care that were
      excellent and those that could be improved. Qualitative data analysis was used to
      discern content clusters and relate them to high and low ratings of patient
      satisfaction. Content analysis revealed that patients perceive and value at least
      seven domains of healthcare in defining outstanding quality (access,
      communication, personality and demeanor of provider, quality of medical care
      processes, care continuity, quality of the healthcare facilities, and office
      staff. All seven were cited as reasons for rating physicians as excellent, while
      four domains (communication, care coordination, interpersonal skills, and
      barriers to access) drove negative ratings. We conclude that patient satisfaction
      ratings are highly influenced by a core of communication and follow-up care.
      Physicians who do not possess these traits will not likely attain high ratings,
      while having these core traits does not necessarily ensure high patient
      satisfaction.

PMID- 17494479
TI  - How to perform your own practice operational assessment.
AB  - It is important to evaluate if your practice is operating as an efficient
      business. This article will provide suggestions on how to evaluate each component
      of your medical business yourself.

PMID- 17494480
TI  - 11 techniques to attract patients to your clinical research studies.
AB  - Many physicians are searching for the "Holy Grail", i.e., the ability to earn
      passive medical income without having to see patients. Unfortunately, that rarely
      exists in most medical practices. However, conducting clinical research studies
      is an opportunity to approach the objective of passive income. This article
      discusses tested techniques to increase the number of patients participating in
      clinical research studies.

PMID- 17494481
TI  - Age to age: insight into managing a multigenerational staff.
AB  - Diversity in age and culture-medical practices and healthcare entities mirror the
      business world in the diversity of culture and age groups among their employees
      and patients. Differences create challenges, but with understanding and skillful
      communication, distinctions become opportunities for growth and excellence. The
      concept we are exploring is that as a generation we are who we are because of
      what was going on in our world during our formative years. We find that just
      naming ourselves aspart ofa group is a good starting point. The objective of this
      article is to identify characteristics of various age groups and to present ways
      to promote harmony and to maximize performance through practical management
      techniques. The goal is to better understand ourselves and each other so that our
      work is more productive and rewarding.

PMID- 17494482
TI  - Team spirit: the key to building a united front.

PMID- 17494483
TI  - Compensation for general surgeons.
AB  - Determining salary compensation for general surgeons is very complex for both
      private and academic-based physician practices. In this paper, the development of
      a plan for private practice general surgeons will be addressed.

PMID- 17494484
TI  - What strategic planning can do for you.
AB  - Whether it's playing chess or planning for retirement, we all have strategies for
      different situations in our lives. So why not apply, strategies in our practice ?
      Companies such as Dell, Wal-Mart, and Home Depot have depended on strategic plans
      to generatel millions of dollars and guide their organizations into the future.
      Although most of our practices are not nearly as large as these companies (except
      maybe Kaiser Permanente), formulating strategies for our practice is vital for
      future growth.

PMID- 17494485
TI  - The medical malpractice crisis: what is the cause? Is there a cure?
AB  - Medical malpractice liability insurance premiums have been escalating for years
      and are at an all-time high. Malpractice reform is highly contentious with
      doctors, insurance companies, and other business interests lobbying to shield
      themselves from the high cost of lawsuits and multi-million dollar awards, and
      trial attorneys and patient advocates claiming that suing is the only recourse
      for people harmed by the healthcare system. Until the courts, lawmakers, and/or
      insurance companies agree on a solution, however, there are several things a
      practice and its administration and physicians can do to minimize the occurrence
      of a malpractice lawsuit. In addition to practicing sound medicine, physicians
      and their staffs must follow sound business policies and customer service
      procedures in their practices.

PMID- 17494486
TI  - 50 strategies for working well with doctors: a staff training tool.
AB  - The relationship between the doctor(s) and the employees of a medical practice is
      a critical one. A good working relationship is key to delivering efficient and
      productive healthcare and to creating a happy work environment for everyone. A
      strained or damaged relationship can lead to serious errors and stress, and
      ultimately it can hurt patients and the practice's bottom line. This article,
      designed as a staff training tool, provides 50 specific strategies for employees
      in a medical practice to use to build strong relationships with the doctor or
      doctors with whom they work. It shows employees specific techniques for building
      trust in their relationships with doctors and reveals what doctors expect and
      hope for in their employees. This article also offers useful techniques for
      dealing with difficult situations. It will also help medical practice employees
      identify and appreciate the importance of their working relationship with the
      doctor(s) in the practice and motivate them to work on improving those
      relationships.

PMID- 17494487
TI  - EMRs: a double-edged sword for coding.

PMID- 17494488
TI  - Creating and promoting a sports performance service offering.
AB  - Many private hospitals and physician groups are exploring the possibility of
      expanding their facilities to include advanced ancillary services. Services such
      as a sports performance center provide additional opportunities for quality
      patient care and at the same time augment the bottom line. By offering additional
      ancillary services, healthcare organizations such as an orthopaedics practice can
      become a full-service center enabling clinicians to more fully provide care to
      their patients. Marketing and promotion play a crucial role in this type of
      service. These activities must be designed and carried out in a way that
      encourages productive results and collaboration as the organization strives to
      position itself as a full-service center and as a sports specialist in its
      community.

PMID- 17494489
TI  - Why your practice must do background checks.
AB  - Hiring qualified staff is critical for a medical practice. As many physicians
      have discovered, taking applicants' resumes on faith can be a mistake. Background
      company searches show that one in three applicants provide false, inaccurate,
      misleading, or incomplete information. Fake degrees, false licenses and
      certifications, and criminal histories are a few of the problems that a proper
      background check can reveal. This article describes further why background checks
      are essential, how to incorporate a background check into your hiring process,
      and some of the legalities involved in the process.

PMID- 17494490
TI  - 2006 year-end ERISA developments plan can recover overpayments.

PMID- 17494491
TI  - The case for undergraduate medical education in healthcare business and
      management.
AB  - Current undergraduate medical education does notprepare students to approach the
      intricacies of healthcare business. This absence within medical education creates
      significant challenges for physicians throughout their careers. The field of
      academic medicine has clearly documented the need for medical education to
      prepare students for practice management, yet there exist only a small number of
      attempts at exposing students to healthcare business and management. The authors
      argue that this curriculum must start at the level ofundergraduate medical
      education. Furthermore, this curriculum must possess the basic components of
      support, integration, practicality, application, and continuation. Fulfilling
      these requirements will allow for the successful adaptation of the healthcare
      business and management curriculum.

PMID- 17494492
TI  - I'm a surgeon, not a teammate.

PMID- 17494493
TI  - Protecting yourself against liability from dangerous employees.

PMID- 17494494
TI  - Consumer-driven health plans: latest challenge to practices' cash flow.
AB  - CDHPs are here to stay. Employers welcome CDHPs because they drive costs away
      from themselves and into the hands of both consumers and provides. The consumer
      will make medical purchase decisions tempered by personal economic
      considerations. The providers are left to figure it all out with the hope their
      cash flow, cost budgets, and customer service will not be negatively impacted. It
      will not be easy. Practices must become educated on how CDHPs work, become
      knowledgeable about specific HSA scenarios in their market, develop optimum
      processes and procedures, and train staff.

PMID- 17494495
TI  - Carbon nanotubes in medical technology.
AB  - One of the more important classes of material to emerge from the recent
      developments in nanotechnology has been the carbon nanotube. A variety of
      nanoscale carbon tube structures have been prepared and this article discusses
      their structure, properties and potential medical applications.

PMID- 17494496
TI  - Radiation sterilisation of advanced drug-device combination products.
AB  - Sterilisation of drug-device combination products presents unique challenges and
      demands some new thinking. Issues such as dose setting and controlling free
      radicals for these ultraclean, high-cost products are discussed together with the
      future advancements required for their efficient terminal sterilisation.

PMID- 17494497
TI  - Reinventing micro-and nanomoulding.
AB  - Recent advances in micro- and nanomoulding techniques are expanding the
      possibilities in polymer processing. New materials and ever more demanding end
      uses have prompted a structured rethink of many of the traditional "rules" and
      led to novel processing and measurement developments that are crucial for
      successful industrial exploitation of micromoulding.

PMID- 17494498
TI  - Regenerative medicine. The industry comes of age.
AB  - The regenerative medicine industry has moved into a new era in which
      commercialisation and not research is the number one priority. To achieve its new
      goal, much has had to change, including the introduction of expert business
      management, simpler but superior products and scalability of manufacture. Mass
      public and political support is supplying both long-term resources and the market
      demand to finally create a sustainable new health-care sector.

PMID- 17494499
TI  - Revised standards for sterilisation: the changes.
AB  - The standards for the three main methods of sterilising medical devices, ethylene
      oxide, radiation and moist heat, have been revised. This article discusses the
      major changes in the requirements, which will need to be addressed to demonstrate
      compliance with the revised standards.

PMID- 17494500
TI  - Risk management of European device clinical studies.
AB  - There is an increasing need to perform clinical studies to support device safety
      and performance claims. This article discusses risks associated with conducting
      European clinical studies of medical devices that are unrelated to risks
      concerning the use of the device. These can jeopardise the success of a clinical
      study regardless of the safety and performance aspects of the device.

PMID- 17494501
TI  - Intelligent drug delivery from the oral cavity.
AB  - A novel drug delivery device that is inserted into the oral cavity is being
      developed to treat chronic diseases and drug addiction.

PMID- 17494502
TI  - Packaging design: basic principles.
AB  - This overview of the critical steps of the packaging design process highlights
      the effectiveness of design change and how it must be accommodated.

PMID- 17494503
TI  - Getting medical devices faster to market.
AB  - Rapid injection moulding provides speed and cost advantages say three medical
      device companies.

PMID- 17494504
TI  - Laser welding thermoplastics.
AB  - The use of infrared absorbers is advised for successful laser transmission
      welding of thermoplastics.

PMID- 17494505
TI  - 50 Hz fatigue testing of large diameter stent grafts.
AB  - An aortic stent graft has been fatigue tested in a system that operates at a
      frequency of 50 Hz. The mode of operation and the results that supplement finite
      element model calculations are described.

PMID- 17494506
TI  - A call to action on health management of populations.

PMID- 17494507
TI  - New, integrated model of care targets risk rather than disease.
AB  - That's the key to getting healthcare costs under control, according to one health
      plan that has reengineered its programming with this concept in mind.

PMID- 17494508
TI  - Healthcare collaboratives focus QI efforts on every patient.
AB  - By working together, dozens of community health centers believe they now have a
      methodology to help bring quality care to every patient.

PMID- 17494509
TI  - Alternative models of care get results in diabetic patients.
AB  - Some experts believe this is the way to improve clinical outcomes, and they're
      doing it by getting nurses and pharmacists more involved.

PMID- 17494510
TI  - Alcoholic cerebellar degeneration: a clinicopathological study of six Japanese
      autopsy cases and proposed potential progression pattern in the cerebellar
      lesion.
AB  - Alcoholic cerebellar degeneration (ACD) is one of the most common neurological
      complications in alcoholics. As far as we know, however, only four Japanese
      autopsy cases of ACD have been reported, and only limited clinicopathological
      data on this disease are now available in Japan. The aims of this study were: (i)
      to examine the clinicopathological correlation of six Japanese autopsy cases of
      ACD, including three asymptomatic cases; and (ii) to elucidate the pattern of
      progression of the cerebellar lesion in ACD. All six alcoholics were
      histopathologically diagnosed as having "pure" ACD without Wernicke's
      encephalopathy. The characteristics of the topographical distribution of the
      cerebellar lesion were as follows. Symptomatic cases (cases 1-3) showed more
      severe and widespread change than asymptomatic cases (cases 4-6). Even in case 6,
      which had the mildest lesion, the anterior vermis developed a moderate change
      (Purkinje cell loss and narrowing of the molecular layer). In cases 4 and 5 with
      more severe and widespread lesions, the superior and posterior vermis and the
      adjacent regions of the superior hemisphere, including the anterior lobe and
      simple lobule, were involved. In all symptomatic cases, the anterior superior
      hemisphere had severe lesions involving the granular cell layer. In contrast to
      asymptomatic cases, all symptomatic cases also had severe to moderate lesions in
      the anterior inferior hemisphere. In cases 1 and 2 with the most severe lesions,
      the moderate to severe changes were distributed in the posterior and inferior
      portions of both the vermis and hemisphere. These findings suggest that in ACD,
      severe lesions successively develop: (i) in the anterior superior vermis; (ii)
      anterior superior hemisphere; (iii) anterior inferior hemisphere; and (iv)
      anterior inferior vermis. In addition, cerebellar symptoms may frequently occur
      if the anterior superior hemisphere and anterior inferior hemisphere, in addition
      to the anterior superior vermis, are involved.

PMID- 17494511
TI  - Ki-67 proliferative index predicts clinical outcome in patients with atypical or
      anaplastic meningioma.
AB  - Meningiomas represent the second most common central nervous system neoplasms in
      adults and account for 26% of all primary brain tumors. Although most are benign,
      between 5% and 15% of meningiomas are atypical (grade II) whereas 1-2% are
      anaplastic meningiomas (grade III). Although histological grade is the most
      relevant prognostic factor, there are some unusual cases in which establishing a
      diagnosis of high-grade meningioma following 2000 World Health Organization (WHO)
      histological criteria is extremely difficult. Therefore, the aim of the present
      study was to evaluate the predictive value of Ki-67 labeling index and its
      contribution to current WHO classification in predicting tumor recurrence and
      overall survival in patients with high-grade meningiomas. A total of 28 patients
      (with 16 atypical meningiomas and 12 anaplastic meningiomas) were evaluated for
      demographic, clinical, radiological and therapeutic variables, and for Ki-67
      immunohistochemistry. Median Ki-67 labeling index in the whole series was 7.0
      (0.5-31.5) with no differences with respect to the histological grade (P = 0.87).
      In the univariate analysis, Ki-67 labeling index and postoperative Karnofsky
      performance status were identified as significant prognostic factors of tumor
      recurrence and overall survival. The multivariate analysis demonstrated that Ki
      67 labeling index is the only independent predictor of both tumor recurrence and
      overall survival. More importantly, this predictive value was maintained in both
      patients with atypical and patients with anaplastic meningioma.

PMID- 17494512
TI  - Morphometric and topographical studies of small neurons in sporadic amyotrophic
      lateral sclerosis spinal gray matter.
AB  - Little attention has been paid to the degeneration of small neurons in ALS spinal
      gray matter. The purpose of the present paper was to undertake morphometric and
      quantitative analysis of the spinal gray matter of 15 ALS patients and compare
      findings to those of five controls. A significant reduction of small neurons in
      the anteromedial and intermediate parts of the gray matter were detected in ALS
      spinal cords with diffuse myelin pallor in the ventral aspects of the
      anterolateral columns outside the corticospinal tracts, and the number of small
      neurons in these areas was decreased significantly depending on the intensity of
      the myelin pallor. There were no significant alterations in the number of small
      neurons in the corresponding areas of ALS spinal cords without diffuse myelin
      pallor or in those of controls. In the posterior parts of the gray matter, there
      were no significant differences in the number of small neurons among ALS patients
      and controls. These findings strongly suggest that diffuse myelin pallor in the
      ventral aspects of anterolateral columns in ALS spinal cords is derived from the
      degeneration of small neurons in the anteromedial and intermediate parts of the
      gray matter.

PMID- 17494513
TI  - Granulomatous tissue response in germinoma, a diagnostic pitfall in endoscopic
      biopsy.
AB  - We report a case of a 24-year-old man with a right thalamic germinoma that
      initially mimicked a granulomatous inflammation, compatible with neurosarcoidosis
      based on clinical symptoms, imaging results and histology of an endoscopically
      navigated biopsy. A second biopsy, prompted by clinical course, and performed
      openly from parieto-lateral revealed the underlying germinoma, obscured in the
      first biopsy by a granulomatous tissue response, particularly at the tumor edge.
      The present case highlights granulomatous inflammatory tissue response on the
      tumor edge of germinoma as a tumor-immanent diagnostic challenge. This diagnostic
      problem is aggravated by stereotactic and endoscopic approaches. We conclude that
      granulomatous inflammation in a specimen obtained by biopsy of a midline lesion
      should always be considered for the differential diagnosis of germinoma.
      Stereotactic and endoscopic surgery should sample several different target points
      within the lesion. Because of tumor heterogeneity of germinoma, the open biopsy
      approach is advantageous compared to endoscopic or stereotactic techniques for
      germinoma and should be considered if a germinoma is in the differential
      diagnosis and if allowed by the clinical situation.

PMID- 17494514
TI  - Acute intermittent porphyria with peripheral neuropathy complicated by small
      fiber neuropathy.
AB  - We describe a 60-year-old male patient with acute intermittent porphyria (AIP)
      who presented with initial abdominal pain and subsequent quadriplegia and
      respiratory failure. Small fiber neuropathy was demonstrated by measuring intra
      epidermal nerve fiber density (IENFD) using protein gene product 9.5 (PGP 9.5)
      immunostaining on three consecutive skin punch biopsies of the distal lower limb.
      The biopsy findings demonstrated some correlation with progression of the
      patient's clinical condition. Neuropathy in AIP can have a small-fiber component
      rather than being solely a large-fiber neuropathy.

PMID- 17494515
TI  - Spinal atypical teratoid/rhabdoid tumor in a 7-year-old boy.
AB  - Reported herein is an unusual case of atypical teratoid/ rhabdoid tumor (AT/RT)
      of the lumbar spine with an intradural extramedullary location in a 7-year-old
      boy. Histologically, this tumor contained rhabdoid cells, pale cells, and sickle
      shaped embracing cells without primitive neuroectodermal tumor (PNET),
      mesenchymal or epithelial components. Immunohistochemical staining showed that
      these tumor cells react positively for epithelial membrane antigen (EMA),
      vimentin, cytokeratin (AE1/AE3), CD99 and neurofilament protein, but negatively
      for INI1 antibody. Chromosome 22q deletion was demonstrated on fluorescence in
      situ hybridization.

PMID- 17494516
TI  - A 2-year-old boy with hypoactivity of neonatal onset and profound developmental
      delay.

PMID- 17494517
TI  - Positive change ahead: February 2007 Leadership Council Meeting.

PMID- 17494518
TI  - The conundrum hormones: evidence vs. experience.

PMID- 17494519
TI  - Holistic health coaching: helping clients in times of transition.

PMID- 17494520
TI  - Midlife transition to HN-BC.

PMID- 17494521
TI  - Inner dancer.

PMID- 17494523
TI  - Loving my self.

PMID- 17494522
TI  - Integral and holistic nursing.

PMID- 17494524
TI  - From a cocoon to a butterfly: energetic evolution during transitions.

PMID- 17494526
TI  - A word on demeaning words.

PMID- 17494525
TI  - How does one live well while dying?

PMID- 17494527
TI  - The Yin and Yang of dogs and cats.

PMID- 17494528
TI  - Building a better vet.

PMID- 17494529
TI  - Who let the dogs in?

PMID- 17494530
TI  - The case of the ruined rodents.

PMID- 17494531
TI  - The scent of sickness.

PMID- 17494532
TI  - Prescribe a pet?

PMID- 17494533
TI  - Healthy Minnesota, real reform.

PMID- 17494534
TI  - Health care reform bill introduced.

PMID- 17494535
TI  - Of mice + medicine.

PMID- 17494536
TI  - Dog pals.

PMID- 17494537
TI  - One medicine--today's imperative.

PMID- 17494538
TI  - Diseases pets and people share.
AB  - Having a companion animal such as a dog, cat, or pocket pet is increasingly
      popular in the United States. With more human-animal interactions come additional
      opportunities for disease exchange. This article highlights common zoonoses
      associated with pets and provides recommendations for preventing disease
      transmission, including hand hygiene, client or patient education, and
      appropriate pet care. The article also discusses human diseases in which animals
      may be mistakenly implicated as the source and the recent identification of human
      diseases such as methicillin-resistant Staphylococcus aureus in companion animal
      populations. The article also calls for the strengthening of integrated animal
      and human surveillance systems and cooperation of medical and veterinary
      practitioners.

PMID- 17494539
TI  - Removing hollywood's smoke screen.

PMID- 17494540
TI  - The legend of Clark Jones.

PMID- 17494541
TI  - The noble profession.

PMID- 17494542
TI  - Calling captain pituitary...

PMID- 17494543
TI  - Semen analysis: the test techs love to hate.
AB  - At the heart of better semen analysis is professionalism. The walls of many labs
      are covered with slogans like, "at the end of every test is a worried patient who
      needs an answer". Semen analysis is no different. At its end is a couple
      desperate to have a child or start a family. In spite of the importance of semen
      analysis in fertility diagnosis and treatment, it remains in most clinical
      laboratories "the neglected laboratory test". The tips and recommendations in
      this article should help any lab improve the quality of semen analysis while
      reducing the effort required to produce better results. Knowledge and simple,
      repeatable procedures, combined with QC and competency benchmarks, can put the
      interest and satisfaction back into a test that is the gateway for fertility
      treatment. After all, what is not to love about a cell that swims and comes in so
      many interesting shapes?

PMID- 17494544
TI  - West Nile virus is still with us.

PMID- 17494545
TI  - Dr. Kjeldsberg's practical ARUP academics.

PMID- 17494546
TI  - Roles determine access rights.

PMID- 17494547
TI  - Federal health policy 2007: opportunities and challenges.

PMID- 17494548
TI  - Summary of avian influenza activity in Europe, Asia, Africa, and Australasia,
      2002-2006.
AB  - Between December 2003 and January 2004 highly pathogenic avian influenza (HPAI)
      H5N1 infections of poultry were declared in China, Japan, South Korea, Laos,
      Thailand, Cambodia, Vietnam, and Indonesia. In 2004 an outbreak was reported in
      Malaysia. In 2005 H5N1 outbreaks were recorded in poultry in Russia, Kazakhstan,
      Mongolia, Romania, Turkey, and Ukraine, and virus was isolated from swans in
      Croatia. In 2004 HPAI H5N1 virus was isolated from smuggled eagles detected at
      the Brussels Airport and in 2005 imported caged birds held in quarantine in
      England. In 2006 HPAI was reported in poultry in Iraq, India, Azerbaijan,
      Pakistan, Myanmar, Afghanistan, and Israel in Asia; Albania, France, and Sweden
      in Europe; and Nigeria, Cameroon, and Niger in Africa; as well as in wild birds
      in some 24 countries across Asia and Europe. In 2003, over 25,000,000 birds were
      slaughtered because of 241 outbreaks of HPAI caused by virus of H7N7 subtype in
      the Netherlands. The virus spread into Belgium (eight outbreaks) and Germany (one
      outbreak). HPAI H5N2 virus was responsible for outbreaks in ostriches in South
      Africa during 2005. HPAI H7N3 virus was isolated in Pakistan in 2004. Low
      pathogenicity avian influenza (LPAI) H5 or H7 viruses were isolated from poultry
      in Italy (H7N3 2002-2003; H5N2 2005), The Netherlands (H7N3 2002), France (H5N2
      2003), Denmark (H5N7 2003), Taiwan (H5N2 2004), and Japan (H5N2 2005). Many
      isolations of LPAI viruses of other subtypes were reported from domestic and wild
      birds. Infections with H9N2 subtype viruses have been widespread across Asia
      during 2002-06.

PMID- 17494549
TI  - Avian influenza in North and South America, 2002-2005.
AB  - Between 2002 and 2005, three outbreaks of highly pathogenic avian influenza
      (HPAI) occurred in the Americas: one outbreak in Chile (H7N3) in 2002, one
      outbreak in the United States (H5N2) in 2004, and one outbreak in Canada (H7N3)
      in 2004. The outbreak in Chile was limited to a large broiler breeder operation
      and a nearby turkey flock and represented the first outbreak of HPAI in that
      country. The outbreak of HPAI in the United States occurred in Texas and was
      limited to one premise where chickens were raised for sale in nearby live-bird
      markets. The outbreak in Canada was the largest of the three HPAI outbreaks,
      involving 42 premises and approximately 17 million birds in the Fraser Valley,
      British Columbia. In each of the HPAI outbreaks, the disease was successfully
      eradicated by depopulation of infected farms. All other reports of infections in
      poultry and isolations from wild bird species pertained to low pathogenicity
      avian influenza (LPAI) viruses. Animal Health Officials in Canada reported
      subtypes H3, H5, and H6 in domestic poultry, and H3, H5, H11, and H13 from
      imported and/or wild bird species. An LPAI H5N2 virus continues to circulate in
      Mexico and the Central American countries of Guatemala and El Salvador. Each
      country reported isolations of H5N2 virus from poultry and the large-scale use of
      inactivated and recombinant H5 vaccines in their AI control programs. In
      Colombia, AI was reported for the first time when antibodies to H9N2 were
      detected in chickens by routine surveillance. Intensive surveillance activities
      in the United States detected AI virus or specific antibodies to 13 of the 16
      hemagglutinin (H1-H13) and all nine neuraminidase subtypes in live-bird markets,
      small holder farms, and in commercial poultry from 29 states. The largest
      outbreak of LPAI in the United States occurred in 2002, when 197 farms were
      depopulated (4.7 million birds) to control an outbreak in Virginia and
      surrounding states. The outbreak was caused by an LPAI H7N2 virus closely related
      to an H7N2 virus that has been circulating in the live-bird marketing system in
      the northeastern United States since 1994.

PMID- 17494550
TI  - Lessons learned from Asian H5N1 outbreak control.
AB  - Numerous lessons have been learned so far in controlling H5N1 avian influenza in
      Asia. Early detection of incursions of virus prevented establishment of the
      disease in several countries, notably Japan, South Korea, and Malaysia. In
      countries where detection of early cases was delayed, infection is endemic and
      has been for three or more years. Control measures implemented in these countries
      need to reflect this finding. Vaccination will continue to be one of the key
      measures used in these endemically infected countries. Used alone, vaccination
      will not result in elimination of H5N1 viruses from a country, but, if used
      correctly, it will markedly reduce the prevalence of and susceptibility to
      infection. Vaccination has already played a valuable role in reducing the adverse
      effects of H5N1 viruses. Mass culling also reduces the level of infection in
      infected areas. However, the long-term benefits are limited in endemically
      infected countries owing to the high probability of reinfection on restocking
      unless other measures are used in parallel. Full epidemiological studies have not
      been conducted in many infected countries. Nevertheless, it is recognized that
      the number of clinical cases does not truly reflect the levels of infection.
      Domestic ducks and large live poultry markets have played a key role in the
      persistence of infection, because they can be infected silently. In tackling this
      disease, countries should adopt integrated control programs using the combination
      of measures best suited to the local environment. All surveillance data should be
      shared, both positive and negative, and should include information on cases of
      infection and disease. Socioeconomic and ecological implications of all control
      measures should be assessed before implementation, especially the impact on the
      rural poor.

PMID- 17494551
TI  - Geographic and temporal distribution of highly pathogenic avian influenza A virus
      (H5N1) in Thailand, 2004-2005: an overview.
AB  - Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) occurred in various
      types of domestic poultry in Thailand during 2004-05. H5N1 viruses were also
      detected in humans and other mammalian species. Infections were mainly detected
      in backyard chickens and domestic ducks. The geographic distribution of the 2004
      outbreaks was widespread throughout Thailand; most outbreaks occurred in the
      Central Region, the southern part of the Northern Region, and the Eastern Region.
      In 2005, the H5N1 outbreaks continued and showed a clustered pattern in four
      provinces in the southern part of the Northern Region and in one province in the
      Central Region. H5N1 HPAI outbreaks caused serious socioeconomic consequences to
      the poultry industry, the social community, farmers' livelihood, and human
      health. After key measures were implemented, the incidence of the outbreaks
      declined remarkably in 2005.

PMID- 17494552
TI  - Avian influenza in Pakistan: outbreaks of low- and high-pathogenicity avian
      influenza in Pakistan during 2003-2006.
AB  - From November 2003 to June 2004 an epidemic of high pathogenicity avian influenza
      (HPAI) virus of subtype H7N3 affected the major layer and broiler-breeder raising
      areas of the country. This was accompanied by an outbreak of low pathogenicity
      avian influenza (LPAI) virus of type H9N2 in broilers and layers, which continued
      during 2005. Subsequently, in February 2006 avian influenza virus (AIV) subtype
      H5N1 was for the first time found in two isolated commercial flocks in this
      country. The HPAI outbreak of 2003-2004 was eventually overcome by enforcing
      biosecurity measures, controlling poultry movements, using inactivated vaccines,
      and introducing a comprehensive AI surveillance network throughout the country.
      However, similar measures undertaken to control H9N2 outbreaks have not been
      successful in the affected areas, with continuing increased mortality and heavy
      production losses in broilers and layers, respectively. A similar strategy has
      been devised to combat the spread of newly introduced H5N1 HPAIV. The description
      of these outbreaks and the results of the control strategy are reported here.

PMID- 17494553
TI  - Surveillance activities and molecular analysis of H5N1 highly pathogenic avian
      influenza viruses from Thailand, 2004-2005.
AB  - Avian influenza (AI) outbreaks were first reported in Thailand in January 2004.
      In the past 2 yr, AI viruses have caused three epidemic waves. Disease prevention
      and control in all aspects have been actively carried out. Active and passive
      surveillance based on clinical observation and laboratory analysis were
      intensively conducted, as well as monitoring of genetic variation of the viruses.
      H5N1 viruses isolated from different avian species from different cases and
      locations were selected. We have sequenced specific genes (HA, NA, M, Ns, and
      part of PB2 genes) of 58 H5N1 isolates, as well as whole genome sequencing of 21
      Thai influenza A (H5N1) viruses isolated during the 2004-2005 outbreak. Cluster
      analysis study showed that AI isolates were identified as highly pathogenic avian
      influenza (HPAI) and belonged to genotype Z. The virus had a multiple basic amino
      acid motif at the cleavage site of HA, deletions in the NA stalk region, a five
      amino acid deletion in the NS1 gene, and genetic markers for amantadine
      resistance in the M2 gene. All 58 H5N1 isolates were closely related and grouped
      into the same cluster, together with isolates from wild birds, cats, tigers, and
      humans. Phylogenetic analysis also revealed that Thai isolates were in the same
      cluster as Vietnamese isolates but aligned in a different cluster from
      Indonesian, Hong Kong, and Chinese viruses. In addition, genetic analysis showed
      that most avian influenza virus (AIV) isolates from Thailand had no major genetic
      changes in each gene such as HA (HA cleavage site, receptor binding site, N-link
      glycosylation site), NA (NA stalk region, oseltamivir resistance marker), M (the
      amantadine resistance marker, host specificity site), NS (five amino acid
      deletion site), and PB2 (host specificity site). All Thai poultry isolates
      contained the amantadine resistance marker while none of them had the oseltamivir
      resistance marker. To this end, the molecular characterization of H5N1 viruses
      from Thailand showed that there were no significant point mutations in the
      critical regions, and there was no evidence of changes in the viruses that
      indicate they are capable of sustained human-to-human transmission.

PMID- 17494554
TI  - Review of rapid molecular diagnostic tools for avian influenza virus.
AB  - Molecular diagnostic tests are commonly used to diagnose avian influenza virus
      because they are sensitive and can be performed rapidly, with high throughput,
      and at a moderate cost. Molecular diagnostic tests recently have proven
      themselves to be invaluable in controlling disease outbreaks around the world.
      Several different methods, including traditional reverse transcription-polymerase
      chain reaction (PCR), real-time reverse transcription-polymerase chain reaction,
      and nucleic acid sequence-based amplification among others, have been described
      for the diagnosis of avian influenza in poultry with many different variations of
      primers, probes, enzymes, etc. Few of these tests have been validated, with the
      understanding that validation should be described as a level of comparison
      testing to show "fitness for purpose." None of the molecular diagnostic tests are
      validated for all species or specimen types that might be presented to a
      diagnostic laboratory. The sensitivity and specificity for all the molecular
      tests are governed by three critical control points, including RNA extraction,
      enzymes used for amplification, and the sequence of primers and probes. The RNA
      extraction step is of particular concern, since high-quality RNA is needed for
      any of the molecular tests. Some sample types, including cloacal (fecal) swabs
      and tissues, are difficult to process, with issues of poor RNA extraction or PCR
      inhibitors being common. The development of internal controls, robotics, and bead
      reagents are providing improved performance of existing tests, and new
      technologies will likely provide better tests for the future. With any molecular
      test, assay assurance must be performed on an ongoing basis, which includes the
      use of proficiency panels to measure test performance.

PMID- 17494555
TI  - Appearance of serum antibodies against the avian influenza nonstructural 1
      protein in experimentally infected chickens and turkeys.
AB  - In order to support eradication efforts of avian influenza (AI) infections in
      poultry, the implementation of "differentiation of infected from vaccinated
      animals" (DIVA) vaccination strategies has been recommended by international
      organizations. These systems enable the detection of field exposure in vaccinated
      flocks, and through this detection, infected flocks may be properly managed, thus
      interrupting the perpetuation of the infectious cycle. A promising system, based
      on the detection of antibodies to the nonstructural 1 (NS1) protein of AI, has
      been deemed a good candidate. However, there are presently no data available, in
      support of this DIVA system, with regard to the kinetics of antibody production
      against the NS1 proteins in poultry following infection. The present
      investigation was undertaken to establish the dynamics of the appearance of anti
      NS1 antibodies in a naive population. Following experimental infection of
      turkeys, antibodies to a peptide spanning the c-terminal of the NS1 protein were
      detected by enzyme-linked immunosorbent assay (ELISA) starting between day 3 and
      day 5 postinfection. In contrast, no antibodies to the NS1 peptide could be
      detected in chickens over the test period. In addition, the turkeys and chickens
      reacted differently at a clinical level to the infection by the H9N2 challenge
      virus. Taken together, these findings indicate that there is a significant
      difference in the viral replication in turkeys and chickens, resulting in a
      variation in the production of antibodies to NS1, as detected by the peptide
      based ELISA used. This fact must be taken into consideration when using a DIVA
      system based on the identification of antibodies to the NS1 protein.

PMID- 17494556
TI  - A universal avian endogenous real-time reverse transcriptase-polymerase chain
      reaction control and its application to avian influenza diagnosis and
      quantification.
AB  - Real-time reverse transcriptase-polymerase chain reaction (RRT-PCR) is becoming
      an established first-line diagnostic assay as well as a precise quantification
      tool for avian influenza virus detection. However, there remain some limitations.
      First, we show that the sensitivity of RRT-PCR influenza detection can be 10- to
      100-fold inhibited in oropharyngeal and cloacal swabs. Adding 0.5 U of heat
      activated Taq DNA polymerase successfully reverses PCR inhibition. Second, an
      excellent strategy for detecting false negative samples is the coamplification of
      an internal control from each sample. We developed a universal avian endogenous
      internal control (bird beta-actin) and apply it to influenza A diagnosis.
      Moreover, this internal control proves useful as a normalizer control for virus
      quantification, because beta-actin gene expression does not change in infected
      vs. uninfected ducks. A combined panel of wild bird cloacal swabs, wild bird
      tissue samples, experimental duck swabs, and experimental duck and chicken tissue
      samples was used to validate the endogenous control. The application of an
      endogenous internal control proves an excellent strategy both for avoiding false
      negative diagnostic results and for standardizing virus quantification studies.

PMID- 17494557
TI  - Development of an M2e-specific enzyme-linked immunosorbent assay for
      differentiating infected from vaccinated animals.
AB  - Vaccination programs for the control of avian influenza (AI) in birds have
      restrictions because of some limited efficacy and the difficulty of
      discriminating between vaccinated and virus-infected poultry. We studied M2e, the
      highly conserved external domain of the influenza A M2 protein, as a potential
      differential diagnostic marker for influenza virus infection. The M2 protein is
      an integral membrane protein, scarcely present on virus particles, but abundantly
      expressed on virus-infected cells. M2e-specific enzyme-linked immunosorbent
      assays (ELISAs) for different avian influenza strains were developed by coating
      the peptides corresponding to the first 18 amino acids, without the first
      methionine, of the universal human consensus M2e sequence and the specific M2e
      sequence of two highly pathogenic AI (HPAI) strains, H7N7 and H5N1. Using the M2e
      ELISAs, M2e-specific antibodies were observed in chickens and ducks
      experimentally infected with H7 or H5 HPAI, respectively, that correlated well
      with hemagglutination inhibition (HI) antibodies. Conversely, sera from chicken
      and ducks inoculated with inactivated AI vaccines were positive for HI test but
      negative for the M2e ELISAs. Moreover, ducks inoculated with inactivated vaccine
      and challenged with a HPAI H5N1 seroconverted for antibodies to the M2e peptide,
      with significantly different levels from those measured between the vaccinated
      and infected groups. These results indicate the potential benefit of a simple and
      specific M2e ELISA in the assessment of the efficacy of vaccination as well as
      for diagnostic and survey applications.

PMID- 17494558
TI  - Identification of sensitive and specific avian influenza polymerase chain
      reaction methods through blind ring trials organized in the European Union.
AB  - Many different polymerase chain reaction (PCR) protocols have been used for
      detection and characterization of avian influenza (AI) virus isolates, mainly in
      research settings. Blind ring trials were conducted to determine the most
      sensitive and specific AI PCR protocols from a group of six European Union (EU)
      laboratories. In part 1 of the ring trial the laboratories used their own methods
      to test a panel of 10 reconstituted anonymized clinical specimens, and the best
      methods were selected as recommended protocols for part 2, in which 16 RNA
      specimens were tested. Both panels contained H5, H7, other AI subtypes, and non
      AI avian pathogens. Outcomes included verification of 1) generic AI
      identification by highly sensitive and specific M-gene real-time PCR, and 2)
      conventional PCRs that were effective for detection and identification of H5 and
      H7 viruses. The latter included virus pathotyping by amplicon sequencing. The use
      of recommended protocols resulted in improved results among all six laboratories
      in part 2, reflecting increased sensitivity and specificity. This included
      improved H5/H7 identification and pathotyping observed among all laboratories in
      part 2. Details of these PCR methods are provided. In summary, this study has
      contributed to the harmonization of AI PCR protocols in EU laboratories and
      influenced AI laboratory contingency planning following the first European
      reports of H5N1 highly pathogenic AI during autumn 2005.

PMID- 17494559
TI  - A fully automated procedure for the high-throughput detection of avian influenza
      virus by real-time reverse transcription-polymerase chain reaction.
AB  - The recent spread of highly pathogenic H5N1 avian influenza (AI) has made it
      important to develop highly sensitive diagnostic systems for the rapid detection
      of AI genome and the differentiation of H5N1 variants in a high number of
      samples. In the present paper, we describe a high-throughput procedure that
      combines automated extraction, amplification, and detection of AI RNA, by an
      already described TaqMan real-time reverse transcription-polymerase chain
      reaction (RRT-PCR) assay targeted at the matrix (M) protein gene of AI virus
      (AIV). The method was tested in cloacal and tracheal swabs, the most common type
      of samples used in AI surveillance, as well as in tissue and fecal samples. A
      robotic system (QIAGEN Biosprint 96) extracted RNA and set up reactions for RRT
      PCR in a 96-well format. The recovery of the extracted RNA was as efficient as
      that of a manual RNA extraction kit, and the sensitivity of the detection system
      was as high as with previously described nonautomated methods. A system with a
      basic configuration (one extraction robot plus two real-time 96-well
      thermocyclers) operated by two persons could account for about 360 samples in 5
      hr. Further characterization of AI RNA-positive samples with a TaqMan RRT-PCR
      specific for H5 (also described here) and/or N1 was possible within 2 hr more. As
      this work shows, the system can analyze up to 1400 samples per working day by
      using two nucleic acid extraction robots and a 384-well-format thermocycler.

PMID- 17494560
TI  - Understanding the complex pathobiology of high pathogenicity avian influenza
      viruses in birds.
AB  - Avian influenza (AI) viruses are a diverse group of viruses that can be divided
      into 144 subtypes, based on different combinations of the 16 hemagglutinin and
      nine neuraminidase subtypes, and two pathotypes (low and high pathogenicity
      [HP]), based on lethality for the major poultry species, the chicken. However,
      other criteria are important in understanding the complex biology of AI viruses,
      including host adaptation, transmissibility, infectivity, tissue tropism, and
      lesion, and disease production. Overall, such pathobiological features vary with
      host species and virus strain. Experimentally, HPAI viruses typically produce a
      similar severe, systemic disease with high mortality in chickens and other
      gallinaceous birds. However, these same viruses usually produce no clinical signs
      of infection or only mild disease in domestic ducks and wild birds. Over the past
      decade, the emergent HPAI viruses have shifted to increased virulence for
      chickens as evident by shorter mean death times and a greater propensity for
      massive disseminated replication in vascular endothelial cells. Importantly, the
      Asian H5N1 HPAI viruses have changed from producing inconsistent respiratory
      infections in 2-wk-old domestic ducks to some strains being highly lethal in
      ducks with virus in multiple internal organs and brain. However, the high
      lethality for ducks is inversely related to age, unlike these viruses in
      gallinaceous poultry, which are highly lethal irrespective of the host age. The
      most recent Asian H5N1 HPAI viruses have infected some wild birds, producing
      systemic infections and death. Across all bird species, the ability to produce
      severe disease and death is associated with high virus replication titers in the
      host, especially in specific tissues such as brain and heart.

PMID- 17494561
TI  - Pathobiology of Asian highly pathogenic avian influenza H5N1 virus infections in
      ducks.
AB  - Ducks and other wild aquatic birds are the natural reservoir of type A influenza
      viruses, which normally are nonpathogenic in these birds. However, the Asian
      highly pathogenic avian influenza (HPAI) viruses have evolved from producing no
      disease or mild respiratory infections in ducks to some strains producing severe
      systemic disease and mortality. To further understand the pathogenicity of these
      strains in ducks, we studied the gross and histologic lesions and tissue
      distribution of viral antigen in 2- and 5-wk-old white Pekin ducks infected with
      different Asian-origin H5N1 AI viruses. Seven of eight 2-wk-old ducks inoculated
      with A/Egret/HK/757.2/02 developed acute disease, including severe neurological
      dysfunction and death. However, this virus killed only two of eight 5-wk-old
      ducks. Two additional viruses, A/Vietnam/1203/04 and A/Crow/Thailand/04, also
      produced high mortality in 2-wk-old ducks. Microscopic lesions and AI viral
      antigen were observed most frequently in the nasal cavity, brain, heart, adrenal
      glands, and pancreas. Another virus, A/Thailand PB/6231/04, killed three of eight
      2-wk-old ducks but did not induce neurological signs. Furthermore, older ducks
      infected with this virus did not present clinical signs or gross lesions, and
      their tissues showed very few microscopic lesions. All the viruses studied
      established systemic infections in both younger and older ducks, with viral
      replication in tissues correlating with the severity of the clinical signs. The
      differences in mortality induced by HPAI H5N1 viruses in ducks are reflected in
      the pathological findings and antigen distribution in tissues. However, the
      observed differences in pathology between ducks infected at different ages is
      unclear and may be associated with a variety of factors including the virus
      strain, host immune response, host cell maturation, and capacity to support viral
      replication.

PMID- 17494562
TI  - Assessing potential pathogenicity of avian influenza virus: current and
      experimental system.
AB  - An avian influenza (AI) isolate can be classified as a high pathogenicity avian
      influenza (HPAI) virus based upon the results of the standard intravenous
      pathogenicity index test; molecular classification, which is derived by
      sequencing the hemagglutinin gene across the site coding for the cleavage site;
      or a combination. However, discordant results between the molecular
      classification and virulence for experimentally infected chickens have been
      observed with several H5 and H7 subtype AI viruses. Because the declaration of
      HPAI virus results in severe effects on trade for the entire country, the gap
      between the genetic and phenotypic markers is an important issue, and it requires
      us to reexamine what should be considered an HPAI virus by the Office
      International des Epizooties standards. To better understand and assess the true
      virulence of the virus, potential pathogenicity of H5 and H7 subtype AI virus
      isolates has been assessed by examining the plaquing efficiency of the virus in
      chicken embryo fibroblast cells, conducting 14-day-old embryo passage and
      selection system, and applying in vitro mutagenesis coupled with reverse
      genetics. The potential value of these complimentary methods in assessing
      potential pathogenicity of the AI virus is discussed.

PMID- 17494563
TI  - Adaptation of influenza A/Mallard/Potsdam/178-4/83 H2N2 virus in Japanese quail
      leads to infection and transmission in chickens.
AB  - To assess the potential of quail as an intermediate host of avian influenza, we
      tested the influenza A/Mallard/ Potsdam/178-4/83 (H2N2) virus to determine
      whether through adaptation a mallard strain can replicate and transmit in quail,
      as well as other terrestrial birds. After five serial passages of lung homogenate
      a virus arose that replicated and transmitted directly to contact cage mates. To
      test whether adaptation in quail led to interspecies transmission, white leghorn
      chickens were infected with the wild-type (mall/178) and quail-adapted (qa
      mall/178) viruses. The results show that mall/178 H2N2 does not establish an
      infection in chickens nor does it transmit, while qa-mall/178 H2N2 infects and
      transmits to contact chickens causing clinical signs like depression and
      diarrhea. Completed sequences indicate six amino acid changes spanning four
      genes, PB2, PB1, HA, and NP, suggesting that the internal genes play a role in
      host adaptation. Further adaptation of qa-mall/178 in white leghorn chickens
      created a virus that replicated more efficiently in the upper and lower
      respiratory tract. Sequence analysis of the chicken-adapted virus points to a
      deletion in the neuraminidase stalk region.

PMID- 17494565
TI  - An avian influenza virus from waterfowl in South America contains genes from
      North American avian and equine lineages.
AB  - Apart from an outbreak in commercial poultry in Chile in 2002, there have been
      few reports of avian influenza in South America. However, surveillance in free
      flying birds has been limited. An avian influenza virus was isolated from a
      Cinnamon Teal (Anas cyanoptera) in Bolivia in 2001 from samples collected for an
      avian influenza virus and avian paramyxovirus surveillance study. This isolate
      was determined to be an H7N3 virus by gene sequencing. Analysis of all eight
      genes revealed that five genes were most closely related to the H7N3 in Chile in
      2002. Two genes were most closely related to North American wild aquatic bird
      virus lineages and one gene was most closely related to an equine influenza virus
      from South America.

PMID- 17494564
TI  - Changing epidemiology and ecology of highly pathogenic avian H5N1 influenza
      viruses.
AB  - The H5N1 virus currently circulating is continuing to evolve, and it has already
      resulted in the extension of its host and geographical range. It is likely that
      H5N1 will become a global problem for the poultry industry. How many of the
      recent H5N1 changes observed have been induced by changing patterns in poultry
      raising? A change in attitude on the use of high-quality vaccines is a change
      that would drastically help in the control of the current epidemic in the poultry
      industry. This article provides an overview of the changing properties that have
      been observed during the current H5N1 outbreaks.

PMID- 17494566
TI  - A simulation model for low-pathogenicity avian influenza viruses in dabbling
      ducks in Europe.
AB  - Anseriformes are the reservoir of low-pathogenicity avian influenza viruses
      (LPAIV). Studies have shown a high LPAIV prevalence associated with low antibody
      detection in a wild duck population in northern European countries, whereas in
      winter areas (Mediterranean basin), low viral detection and high seroprevalence
      were observed. In order to gain insight into the role played by both population
      recruitment and migration on AIV persistence, an epidemiological model was
      developed. A susceptible, infectious and removed (immune or dead)-individuals
      model coupling population and infection dynamics was developed to simulate LPAIV
      circulation in dabbling ducks throughout the entire year. The transmission
      coefficient (beta) was calculated using the original dataset of published works,
      whereas dabbling duck demographic parameters were obtained from the literature.
      The estimated host density threshold for virus persistence is 380 susceptible
      individuals per day whereas the critical community size needed for maintaining
      the virus throughout the winter has been estimated to be about 1200 individuals.
      The model showed peaks of viral prevalence after nesting and during the moult
      period because of population recruitment and high host density, respectively.
      During the winter and spring periods, the viruses reach the minimal endemic level
      and local extinction is highly probable because of stochastic phenomena,
      respectively 80% and 90% of probabilities. The most sensitive parameters of the
      model are the recruitment rate of young susceptible animals and the duration of
      virus shedding.

PMID- 17494567
TI  - Phylogenetic analysis of low-pathogenicity avian influenza H6N2 viruses from
      chicken outbreaks (2001-2005) suggest that they are reassortants of historic
      ostrich low-pathogenicity avian influenza H9N2 and H6N8 viruses.
AB  - Low-pathogenicity (LPAI) and high-pathogenicity (HPAI) avian influenza viruses
      are periodically isolated from South African ostriches, but during 2002 the first
      recorded outbreak of LPAI (H6N2) in South African chickens occurred on commercial
      farms in the Camperdown area of KwaZulu/Natal (KZN) Province. Sequence analysis
      of all eight genes were performed and phylogenetic analysis was done based on the
      hemagglutinin and neuraminidasc sequences. Results from phylogenetic analyses
      indicated that the H6N2 chicken viruses most likely arose from a reassortment
      between two South African LPAI ostrich isolates: an H9N2 virus isolated in 1995
      and an H6N8 virus isolated in 1998. Two cocirculating sublineages of H6N2 viruses
      were detected, both sharing a recent common ancestor. One of these sublineages
      was restricted to the KZN province. The neuraminidase gene contained a 22-amino
      acid deletion in the NA-stalk region, which is associated with adaptation to
      growth in chickens, whereas the other group, although lacking the NA-stalk
      deletion, spread to commercial farms in other provinces. The persistence of
      particular H6N2 types in some regions for at least 2 yr supports reports from
      Asia and southern California suggesting that H6N2 viruses can form stable
      lineages in chickens. It is probable that the ostrich H6N8 and H9N2 progenitors
      of the chicken H6N2 viruses were introduced to ostriches by wild birds.
      Ostriches, in which AI infections are often subclinical, may serve as mixing
      vessels for LPAI strains that occasionally spill over into other poultry.

PMID- 17494568
TI  - Persistence of H5 and H7 avian influenza viruses in water.
AB  - Although fecal-oral transmission of avian influenza viruses (AIV) via
      contaminated water represents a recognized mechanism for transmission within wild
      waterfowl populations, little is known about viral persistence in this medium. In
      order to provide initial data on persistence of H5 and H7 AIVs in water, we
      evaluated eight wild-type low-pathogenicity H5 and H7 AIVs isolated from species
      representing the two major influenza reservoirs (Anseriformes and
      Charadriiformes). In addition, the persistence of two highly pathogenic avian
      influenza (HPAI) H5N1 viruses from Asia was examined to provide some insight into
      the potential for these viruses to be transmitted and maintained in the
      environments of wild bird populations. Viruses were tested at two temperatures
      (17 C and 28 C) and three salinity levels (0, 15, and 30 parts per thousand sea
      salt). The wild-type H5 and H7 AIV persistence data to date indicate the
      following: 1) that H5 and H7 AIVs can persist for extended periods of time in
      water, with a duration of infectivity comparable to AIVs of other subtypes; 2)
      that the persistence of H5 and H7 AIVs is inversely proportional to temperature
      and salinity of water; and 3) that a significant interaction exists between the
      effects of temperature and salinity on the persistence of AIV, with the effect of
      salinity more prominent at lower temperatures. Results from the two HPAI H5N1
      viruses from Asia indicate that these viruses did not persist as long as the wild
      type AIVs.

PMID- 17494569
TI  - H9N2 influenza viruses from Israeli poultry: a five-year outbreak.
AB  - Since 2000, hundreds of H9N2 viruses have been isolated from all types of
      domestic birds. Although H9N2 is a low-pathogenicity virus, disease has been
      observed in all types of poultry in the field. Clinical signs ranged from very
      mild disease to high morbidity and mortality when the virus was associated with a
      secondary pathogen. Because of the wide range of the virus and the great losses
      it caused, initially a local vaccination program was implemented, but mass
      vaccination was quickly authorized. A local strain, isolated in 2002 was selected
      and is currently in use as an inactivated vaccine. An intensive operation is in
      progress to characterize the isolates. Several genes (hemagglutinin [HA],
      neuraminidase, nonstructural protein, nucleoprotein, and matrix) were sequenced,
      revealing three main groups: the first group included two isolates from 2000, the
      second group included isolates from 2001 to the beginning of 2003, and the third
      group included all isolates from 2003 to date. The differences between the second
      and third groups, in a part of the HA gene, ranged from 3.49% to 6.97% (average
      4.57%) of the nucleotides. Similar differences were recorded in the other tested
      genes. These data could indicate the probable introduction of distinct progenitor
      viruses into the Israeli poultry population. Furthermore, sequencing of the HA
      protein of some Israeli isolates revealed the presence of L216 in the binding
      site; this finding was typical of the H9N2 viruses isolated from humans, which
      raises the possibility of an influence on host specificity and virulence.

PMID- 17494570
TI  - Practicalities of the implementation of a vaccination campaign for avian
      influenza.
AB  - Emergency vaccination for avian influenza (AI) infections caused by viruses of
      the H5 or H7 subtypes has been used in several instances over the past years. It
      has been applied primarily in the chicken and turkey industry with the general
      objective of controlling, and in some instances eradicating, infection. The use
      of vaccination as a tool to eradicate AI requires the enforcement of a
      coordinated set of control and monitoring measures. In fact, only certain
      attempts at eradicating AI with the support of vaccination have been successful,
      and the outcome of the vaccination campaign has been shown to depend greatly on
      effective application of the field strategy that complemented the vaccination
      program. While it is taken for granted that the product and companion diagnostic
      test are suitable for that given situation, a monitoring system must be in place
      to promptly identify whether vaccinated birds have been field exposed, and the
      latter should be dealt with in an appropriate manner, avoiding the spread of
      infection to other premises. Prophylactic vaccination could also become a tool
      for AI management in the European Union, provided that its application is based
      on a systematic assessment of AI risk. The correct use of this tool can be a
      valuable support for the control of AI in poultry, with the added value of
      limiting the economic losses to the industry and to the taxpayer. Eventually,
      this will also reduce human exposure to potentially dangerous viruses.

PMID- 17494571
TI  - Within-flock mortality during the high-pathogenicity avian influenza (H7N7)
      epidemic in The Netherlands in 2003: implications for an early detection system.
AB  - Daily within-flock mortality data, from a few days before until a few days after
      onset of increased mortality, from H7N7-infected flocks were analyzed with
      nonlinear regression for layer (organic and free-range or caged), broiler, and
      turkey flocks. The following notification thresholds were recommended for The
      Netherlands: 1) organic layer flocks, broiler flocks, and turkey flocks < or = 11
      wk of age: > or = 0.5% mortality/day for two consecutive days; 2) layer flocks
      with birds housed in cages: > or = 0.25% mortality/day for two consecutive days;
      3) turkey flocks > or = 16 wk of age: > or = 1% mortality/day for two consecutive
      days. Notification of increased mortality to the veterinary authorities should
      take place on the second day of increased mortality. Interpretation of mortality
      thresholds should be on the level of the poultry barn in which clinical problems
      arise. Because of nonoptimal specificity of proposed thresholds (mortality
      possibly caused by other diseases), use of PCR-diagnostics (results within 24 hr)
      without costs to the individual farmer should be promoted to exclude avian
      influenza in suspect clinical situations in order to minimize negative economic
      consequence for farmers and stimulate notification by farmers and veterinary
      practitioners.

PMID- 17494572
TI  - The roles of national and provincial diagnostic laboratories in the eradication
      of highly pathogenic H7N3 avian influenza virus from the Fraser Valley of British
      Columbia, Canada.
AB  - In February 2004 a highly pathogenic avian influenza outbreak erupted in the
      Fraser Valley of British Columbia, Canada. The index farm was a chicken broiler
      breeder operation comprising two flocks, 24 and 52 wk of age. Birds in the older
      flock presented with a mild drop in egg production and a small increase in
      mortality. Pathological specimens taken from the older flock were submitted to
      the provincial veterinary diagnostic laboratory from which an influenza A virus
      was isolated. While still under investigation by the provincial veterinary
      authorities, a spike in mortality was observed in birds belonging to the younger
      flock. Diagnostic material from both flocks was forwarded to the Canadian Food
      Inspection Agency's National Centre for Foreign Animal Disease. A low
      pathogenicity H7N3 virus was detected in the older flock and a novel highly
      pathogenic H7N3 virus was found in specimens collected from the younger flock.
      Despite destruction and disposal of birds on the index farm, the virus spread to
      adjacent farms. Given the high density of poultry operations in the Fraser Valley
      and the high level of integration amongst industry support services, a total of
      approximately 17 million chickens, turkeys, ducks, geese, and speciality birds
      were put at immediate risk. Despite movement controls the virus spread and
      established itself in three distinct clusters. To prevent further spread,
      healthy, marketable birds outside of the surveillance areas were pre-emptively
      slaughtered. Although highly pathogenic avian influenza is a federal
      responsibility, the successful control and eradication of this outbreak would not
      have been possible without the cooperative involvement of federal and provincial
      diagnostic laboratories. The success of this collaboration was partly responsible
      for the formation of a national avian influenza laboratory network.

PMID- 17494573
TI  - After the outbreak: how the British Columbia commercial poultry industry
      recovered after H7N3 HPAI.
AB  - In spring 2004, an outbreak of highly pathogenic avian influenza (HPAI), subtype
      H7N3, occurred in the Fraser Valley of British Columbia, Canada. The active
      outbreak lasted more than 90 days; 42 commercial poultry farms were identified as
      infected premises, and more than 17 million birds were culled. Through the
      depopulation of HPAI-positive farms and the strategic depopulation of adjacent
      test-negative farms, a total of 410 commercial poultry farms were emptied. The
      goals for the commercial poultry industry were to expedite restocking, reduce
      nonproductive downtime, negotiate equitable financial compensation, review and
      restructure emergency disease response plans, and identify and implement
      mitigation strategies. After the outbreak, multijurisdictional reviews identified
      the strengths and weaknesses of the outbreak control strategy. Lessons learned
      were incorporated into current emergency disease response protocols for both
      industry and government. The industry-led challenge to initial compensation
      values, especially for specialty poultry and breeder birds, resulted in a review
      of the federal Health of Animals Act. The British Columbia poultry industry, in
      collaboration with the British Columbia Ministry of Agriculture and Lands,
      developed an Enhanced Biosecurity Initiative that included the identification of
      mandatory on-farm biosecurity standards for commercial producers, an educational
      biosecurity self-assessment guide, and provisions for a producer self-quarantine
      to be enacted upon the first suspicion of disease.

PMID- 17494574
TI  - The challenge of controlling notifiable avian influenza by means of vaccination.
AB  - Avian influenza (AI) is an Office International des Epizooties listed disease
      that has become a disease of great importance both for animal and human health.
      The increased relevance of AI in animal and human health has highlighted the lack
      of scientific information on several aspects of the disease, which has hampered
      the adequate management of some of the recent crises. Millions of animals have
      died, and there is growing concern over the loss of human lives and over the
      management of the pandemic potential. The present article reviews the currently
      available control methods for notifiable AI infections in poultry. The
      application of control policies, ranging from stamping out to emergency and
      prophylactic vaccination, is discussed on the basis of data generated in recent
      outbreaks and in light of new regulations, also in view of the maintenance of
      animal welfare. Poultry veterinarians working for the industry or for the public
      sector represent the first line of defense against the pandemic threat and for
      the prevention and control of this infection in poultry and in wild birds.

PMID- 17494575
TI  - Effect of vaccination on transmission of HPAI H5N1: the effect of a single
      vaccination dose on transmission of highly pathogenic avian influenza H5N1 in
      Peking ducks.
AB  - The highly pathogenic H5N1 avian influenza virus is widespread among domestic
      ducks throughout Southeast Asia. Many aspects of the poultry industry and social
      habits hinder the containment and eradication of AI. Vaccination is often put
      forward as a tool for the control of AI. However, vaccination will only lead to
      eradication when it reduces the virus spread to such an extent that herd immunity
      is obtained. To study the effect of a single vaccination dose on the transmission
      of H5N1 in domestic ducks we performed experiments in which infected and
      uninfected ducks were housed together and the infection chain was monitored by
      means of virus isolation and serology. Specifically, Peking ducks were vaccinated
      with A/Chicken/Mexico/232/94/ CPA H5N2 and challenged with A/Chicken/GxLA/1204/04
      H5N1 one week after vaccination. In both the control and vaccinated groups all
      inoculated and contact animals were quickly infected. However, the disease signs
      and mortality differed between the control and treatment groups. This finding may
      have important implications for the control of H5N1 by means of vaccination.

PMID- 17494576
TI  - Efficacy of an inactivated and a fowlpox-vectored vaccine in Muscovy ducks
      against an Asian H5N1 highly pathogenic avian influenza viral challenge.
AB  - The efficacy of an inactivated vaccine containing the Eurasian isolate
      A/chicken/Italy/22A/98 H5N9 (H5N9-It) was compared with that of the fowlpox
      vectored TROVACTM-AIV H5 (rFP-AIV-H5) vaccine against an H5N1 highly pathogenic
      avian influenza challenge. Five-week-old Muscovy ducks were vaccinated with
      either H5N9-It (0.5 ml) or rFP-AIV-H5 (5 log10 50% tissue culture infectious dose
      (TCID50)/dose), followed by a boost at 7 wk of age with the same vaccine (1.0 ml
      of H5N9-It or 5 log10 TCID50/dose rFP-AIV-H5), and a challenge at 9 wk of age
      with 10(7) egg infectious dose (lethality 50%) of A/crested eagle/
      Belgium/01/2004 (H5N1). All unvaccinated challenged birds showed severe nervous
      signs (loss of balance, torticollis) starting 7 days postinfection (dpi). None of
      the vaccinated ducks showed these nervous signs. Shedding was measured in
      oropharyngeal and cloacal swabs, sampled from 3 to 19 dpi by titration in chicken
      embryo fibroblasts and by real-time reverse transcription-polymerase chain
      reaction. Virus shedding was significantly higher in oropharyngeal compared to
      cloacal swabs. Both vaccines reduced the percentage of positive swabs and the
      viral load in the swabs, but the reduction was higher with the H5N9-It vaccine.
      The inactivated vaccine induced hemagglutination inhibition (HI) titers (5.4
      log2) that were boosted after the second administration (7.5 log2). rFP-AIV-H5
      induced HI titers were lower (3 log2 only after the second administration), most
      probably because the fowlpox vector does not replicate in ducks. Altogether,
      these results indicate that significant protection from clinical signs and
      reduction in virus shedding may be achieved in ducks with conventional
      inactivated or fowlpox-vectored vaccine as compared with nonvaccinated challenged
      control birds.

PMID- 17494577
TI  - Efficacy of two H5N9-inactivated vaccines against challenge with a recent H5N1
      highly pathogenic avian influenza isolate from a chicken in Thailand.
AB  - The objective of this study was to compare the efficacy of two avian influenza
      (AI) H5-inactivated vaccines containing either an American (A/turkey/Wisconsin/68
      H5N9; H5N9-WI) or a Eurasian isolate (A/chicken/Italy/22A/98 H5N9; H5N9-It).
      Three-week-old specific pathogen-free chickens were vaccinated once and
      challenged 3 wk later with a H5N1 highly pathogenic AI (HPAI) virus isolated from
      a chicken in Thailand in 2004. All unvaccinated challenged birds died within 2
      days, whereas 90% and 100% of chickens vaccinated with H5N9-WI and H5N9-It,
      respectively, were protected against morbidity and mortality. Both vaccines
      prevented cloacal shedding and significantly reduced oral shedding of the
      challenge HPAI virus. Additional chickens (vaccinated or unvaccinated) were
      placed in contact with the directly challenged birds 18 hr after challenge. All
      unvaccinated chickens in contact with unvaccinated challenged birds died within 3
      days after contact, whereas unvaccinated chickens in contact with vaccinated
      challenged birds either showed a significantly delayed mortality or did not
      become infected. All vaccinated contacts were protected against clinical signs,
      and most chickens did not shed detectable amount of HPAI virus. Altogether, these
      data indicate that both vaccines protected very well against morbidity and
      mortality and reduced or prevented shedding induced by direct or contact exposure
      to Asian H5N1 HPAI virus.

PMID- 17494578
TI  - The new World Organisation for Animal Health standards on avian influenza and
      international trade.
AB  - In 2002, the World Organisation for Animal Health began a review of the chapter
      on avian influenza by convening a group of experts to revise the most recent
      scientific literature. The group drafted the initial text that would provide the
      necessary recommendations on avian influenza control and prevention measures. The
      main objectives of this draft were to provide clear notification criteria, as
      well as commodity-specific, risk-based mitigating measures, that would provide
      safety when trading and encourage transparent reporting.

PMID- 17494579
TI  - Assessment of the risk of introduction of H5N1 HPAI virus from affected countries
      to the U.K.
AB  - The Department for Environment, Food and Rural Affairs (Defra) has monitored
      epidemiologic developments following outbreaks of H5N1 in Asia since the
      beginning of 2004 and publishes risk assessments as the situation evolves. The
      U.K. applies safeguard measures that reflect EU rules to enable imports to
      continue when they present negligible risk. Defra risk assessments (RA) identify
      possible pathways by which the H5N1 virus may be introduced to the U.K. These
      assessments provide a basis for identifying appropriate surveillance activities
      to ensure early detection, should the virus be introduced, and disease control
      measures to be taken, should the virus be detected in the U.K. Nevertheless,
      these assessments have highlighted that many fundamental uncertainties still
      remain. These uncertainties center on the geographic and species distribution of
      infection outside Asia and the means of dissemination of the virus. However, the
      evolving developments demonstrated that regulatory decisions had to be made
      despite these uncertainties. Improvements in our current RA abilities would
      greatly benefit from systematic studies to provide more information on the
      species susceptibility, dynamics of infection, pathogenesis, and ecology of the
      virus along with possible pathways by which the H5N1 virus may be disseminated.
      Such an approach would assist in reducing uncertainties and ensuring that
      regulatory risk management measures are regularly reviewed by taking into account
      the most recent scientific evidence. The likelihood of the persistence of H5N1
      outside Asia in the coming years and the effects of control programs in Asia and
      other affected regions to reduce the prevalence of infection are also important
      factors.

PMID- 17494580
TI  - Assessing the probability of the presence of low pathogenicity avian influenza
      virus in exported chicken meat.
AB  - Avian influenza (AI) is a disease of concern for the poultry industry. In its
      highly pathogenic form, AI viruses (AIVs) can cause a high morbidity and case
      fatality rate as well as severe economic consequences. Low pathogenic AIVs
      (LPAIVs), in contrast, only cause localized infections in the respiratory and
      gastrointestinal tracts of affected birds. Although there is apparently
      sufficient scientific evidence documenting the absence of LPAIV in poultry meat,
      several countries still place restrictions for international trade of poultry
      meat on LPAIV-infected countries. These restrictions are extremely trade
      disruptive and entail significant losses to the poultry industry. This article
      presents a quantitative approach to assess the probability of LPAIV presence in
      chicken meat and provides a model that can be tailored to reflect the
      epidemiology of LPAIV and surveillance systems in different countries. Results
      show that the probability of introducing LPAIV through chicken meat imports is
      insignificant.

PMID- 17494581
TI  - Surveillance for avian influenza in Nepal 2004-2005.
AB  - Highly pathogenic avian influenza has not been reported in Nepal to date.
      Surveillance for the presence of avian influenza viruses was conducted in 16
      districts of Nepal from February 2004 to December 2005. Four hundred forty-six
      serum samples were collected from ducks, chickens, and pigeons and tested for
      antibodies to all influenza A viruses by competitive enzyme-linked immunosorbent
      assay (C-ELISA). Any sera positive by C-ELISA were tested for antibodies to H5,
      H7, and H9 influenza viruses by hemagglutination inhibition tests. One hundred
      and thirty-five cloacal swabs from healthy ducks and chickens were tested by
      commercial avian influenza antigen detection kits. A further 13 tissue samples
      from diseased birds were tested for the presence of virus by virus isolation in
      eggs, cell culture, and immunohistochemistry. No influenza viruses were detected
      in any of the tissues or swabs. All serum samples collected before October 2005
      were negative for antibodies. The first sera positive for antibodies were
      collected on October 13, 2005, which were determined to be of the H9N2 subtype.
      This is the first report of serologic evidence of an avian influenza virus
      infection in Nepal.

PMID- 17494582
TI  - The 2005/2006 avian influenza monitoring of wild birds and commercial poultry in
      Switzerland.
AB  - In October 2005, the second Swiss national avian influenza monitoring in wild
      waterfowl and commercial poultry with free range management started. Cloacal
      swabs were examined by real-time reverse transcription-polymerase chain reaction
      for both M gene of influenza A virus and H5 subtype. The monitoring (more than
      2000 samples tested) documented the introduction of H5N1 in Swiss wild waterfowl
      in mid-February 2006. Until the end of March, 29 water bird carcasses were found
      H5 positive. In the same period, domestic poultry flocks with a permit of free
      range management were kept under surveillance, with negative results.

PMID- 17494583
TI  - Emergency assistance in laboratory development for control of avian influenza in
      Laos and Cambodia.
AB  - Avian influenza (AI) diagnostic laboratories in Laos and Cambodia have been
      established recently to conduct AI surveillance and diagnostic tests to
      coordinate regional efforts for the control of highly pathogenic avian influenza
      (HPAI) in South East Asia. Two laboratories have been provisioned with equipment,
      supplies, and reagents for routine diagnostic testing. Laboratory staff has
      received training to conduct serologic and virologic tests for isolation and
      identification of AI virus. Development of a disease reporting system and an AI
      surveillance program is in progress in Laos and Cambodia. There are plans to
      further upgrade laboratory facilities and to provide more comprehensive and
      advanced molecular diagnostic tests for control of HPAI in Laos and Cambodia.
      These two countries are on the frontline in the battle to fight HPAI H5N1 virus
      and to prevent it from spreading to other regions and mutating to a major human
      pathogen.

PMID- 17494584
TI  - Avian influenza in Chile: a successful experience.
AB  - Avian influenza (AI) was diagnosed in May 2002 for the first time in Chile and
      South America. The epidemic was caused by the highly pathogenic AI (HPAI) virus
      subtype H7N3 that emerged from a low pathogenic virus. The index farm was a
      broiler breeder, located in San Antonio, V Region, which at the time was a
      densely populated poultry area. Stamping of 465,000 breeders, in 27 sheds, was
      immediately conducted. Surveillance activities detected a second outbreak, 1 wk
      later, at a turkey breeding farm from the same company. The second farm was
      located 4 km from the index case. Only 25% of the sheds were infected, and 18,500
      turkeys were destroyed. In both outbreaks, surveillance zones and across-country
      control measures were established: prediagnosis quarantine, depopulation,
      intensive surveillance, movement control, and increased biosecurity. Other
      measures included cleaning, disinfection, and controlling the farms with
      sentinels to detect the potential presence of the virus. Zoning procedures were
      implemented to allow the international trade of poultry products from unaffected
      areas. Positive serologic results to H5N2 virus also were detected in other
      poultry farms, but there was no evidence of clinical signs or virus isolation.
      Epidemiological investigation and laboratory confirmation determined that
      positive serology was related to a contaminated imported batch of vaccine against
      inclusion body hepatitis. All actions taken allowed the control of the epidemic,
      and within 7 mo, Chile was free of AI. Epidemic and control measures that
      prevented further spread are described in this article, which illustrates the
      importance of a combination of control measures during and after an outbreak of
      AI. This study is a good example of how veterinary services need to respond if
      their country is affected by HPAI.

PMID- 17494585
TI  - Effect of different temperatures on the stability of avian influenza reference
      reagents.
AB  - The production and supply of reference reagents for the diagnosis of avian
      influenza (AI) is one of the duties of the World Organization for Animal Health
      reference laboratories. The lyophilized reagents are routinely shipped on dry ice
      to both national and international clients. In order to determine the effect of
      different short-term storage temperatures on the activity of AI reference
      reagents, vials containing lyophilized avian influenza A antigens and antisera
      preparations were maintained at 4 C, 22 C, and 37 C over a 21-day period. At days
      0, 3, 7, 14, and 21 the reagents were titrated using the hemagglutination test,
      the hemagglutination inhibition test, or the agar gel immunodiffusion test
      (AGID). All of the AI antigens that were kept at 4 C and 22 C retained
      hemagglutinating activity for at least 21 days, but when they were stored at 37 C
      several lost their hemagglutinating activity. All of the reference antisera
      tested were still able to inhibit hemagglutination after 21 days, and the antigen
      used in AGID also gave clear results after 21 days even after incubation at 37 C.
      Our results therefore indicate that lyophilized avian influenza antigens maintain
      their hemagglutinating activity at temperatures between 4 C and 22 C for at least
      21 days, and both antisera and antigens prepared for AGID remain stable for 21
      days between 4 C and 37 C. This information will allow for alternative shipping
      temperatures than those presently recommended, in addition to the short-term
      storage of these reagents at nonrefrigerated temperatures.

PMID- 17494586
TI  - Rapid detection of highly pathogenic avian influenza H5N1 virus by TaqMan reverse
      transcriptase-polymerase chain reaction.
AB  - Highly pathogenic avian influenza (AI) H5N1 viruses have been spreading from Asia
      since late 2003. Early detection and classification are paramount for control of
      the disease because these viruses are lethal to birds and have caused fatalities
      in humans. Here, we described TaqMan reverse transcriptase-polymerase chain
      reaction assays for rapid detection of all AI viruses (influenza type A) and for
      identification of H5N1 of the Eurasian lineage. The assays were sensitive and
      quantitative over a 10(5)-10(6) linear range, detected all of the tested AI
      viruses, and enabled differentiation between H5 and H7 subtypes. These tests
      allow definitive confirmation of an AI virus as H5 within hours, which is crucial
      for rapid implementation of control measures in the event of an outbreak.

PMID- 17494587
TI  - Validated H5 Eurasian real-time reverse transcriptase-polymerase chain reaction
      and its application in H5N1 outbreaks in 2005-2006.
AB  - Real time reverse transcriptase (RRT)-polymerase chain reaction (PCR) for the
      detection of Eurasian H5 avian influenza virus (AIV) isolates was adapted from an
      existing protocol, optimized, and validated using a number of genetically diverse
      H5 isolates (n = 51). These included 34 "Asian lineage" H5N1 highly pathogenic
      avian influenza (HPAI) viruses (2004-2006), plus 12 other H5 isolates from
      poultry outbreaks and wild birds in the Eastern Hemisphere (1996-2005). All 51
      were positive by H5 Eurasian RRT-PCR. Specificity was assessed by testing
      representative isolates from all other AL virus subtypes (n = 52), non-AI avian
      pathogens (n = 8), plus a negative population of clinical specimens derived from
      AI-uninfected wild birds and poultry (n = 604); all were negative by H5 Eurasian
      RRT-PCR. RNA was directly extracted from suspect HPAI H5N1 clinical specimens
      (Africa, Asia, and Europe; 2005-2006; n = 58) from dead poultry and wild birds,
      and 55 recorded as positive by H5 Eurasian RRT-PCR: Fifty-one of these 55 were in
      agreement with positive AIV isolation in embryonated chickens' eggs. H5 Eurasian
      RRT-PCR was invaluable in H5 outbreak diagnosis and management by virtue of its
      rapidity and high degree of sensitivity and specificity. This method provides a
      platform for automation that can be applied for large-scale intensive
      investigations, including surveillance.

PMID- 17494588
TI  - A real-time TaqMan RT-PCR method for neuraminidase type 1 (N1) gene detection of
      H5N1 Eurasian strains of avian influenza virus.
AB  - This work describes the development of a real-time RT-PCR (RRT-PCR) procedure for
      detection of the N1 gene from avian influenza virus (AIV), based on the use of
      specific primers and a TaqMan-MGB (minor groove binder) probe. Nucleotide
      sequences of the neuraminidase type 1 gene from a collection of H5N1 Eurasian
      strains of AIV were aligned using ClustalW software. Conserved regions were
      located and used to design specific primers and a TaqMan-MGB probe using Primer
      Express software. A one-step RRT-PCR method was optimized using RNA from the
      Turkey 2005 H5N1 strain of AIV and can be completed in about 2 hr once the RNA is
      extracted from the sample. The specificity of the assay was assessed with non-N1
      AIV strains, another related avian virus, and different avian tissue samples from
      healthy animals. Sensitivity was determined using 10-fold serial dilutions of the
      H5N1 Turkey 2005 strain and was compared with the generic RRT-PCR detection
      method, targeted at the matrix protein gene of AIV, commonly used at the Spanish
      AIV National Reference Laboratory. The N1 detection method proved to be even more
      sensitive than the generic (matrix-based) method, allowing a very quick
      confirmation (or discarding) of any Eurasian N1 strain when a positive result was
      obtained with the matrix RRT-PCR assay. Combined with RRT-PCR tests for general
      detection of AIV and H5 typing in use at the NRL, the procedure here described
      allows characterizing of any H5N1 Eurasian AIV strain in a field sample within a
      working day.

PMID- 17494589
TI  - Surveillance on avian influenza in Bulgaria.
AB  - Nota de Investigacon Bulgaria has a surveillance program on avian influenza to
      keep a close watch on health of poultry, exotic birds, and wild birds. The
      samples include sera for serologic examination, and carcasses, tissue samples,
      tracheal and cloacal swabs, and feces for virologic examination. The number of
      samples depends on the epizootic situation in the country and in neighboring
      countries. Migration and resting and living areas of wild birds also are under
      consideration. The territory of Bulgaria is divided into 28 regions. For each of
      these regions, there are exact types and numbers of samples, depending on
      latitude, water reservoir, farms, and backyards. Since October 2005, surveillance
      has become harder because of the situation in Romania and Turkey. Since 2006, the
      number of samples has vastly increased.

PMID- 17494590
TI  - Sensitive and specific detection of influenza virus A subtype H5 with real-time
      PCR.
AB  - Avian influenza is a serious threat to both animal and human health. To enable
      cutting-edge research in this field, we developed a molecular test on the basis
      of real-time polymerase chain reaction (real-time PCR), which detects influenza
      virus RNA. The test enables highly sensitive detection of influenza virus A and B
      strains, including H5N1, and specific identification of influenza A virus H5
      subtypes. The kit was tested against a broad panel of influenza A and B subtypes
      and other respiratory viruses in collaboration with worldwide authoritative
      laboratories and shows a very high specificity and sensitivity. An internal
      control verifies RNA extraction as well as real-time PCR success. With this kit,
      rapid and reliable detection of influenza A and B viruses and identification of
      H5 subtypes can be achieved.

PMID- 17494591
TI  - Pathobiology of H9N2 avian influenza virus in Japanese quail (Coturnix coturnix
      japonica).
AB  - Clinical signs, serologic response, viral contents of the trachea and intestine,
      and histopathological and ultrastructural changes of the tracheal epithelium of
      Japanese quail experimentally infected with field isolate of H9N2 avian influenza
      were studied. Vaccinated and unvaccinated quail were inoculated with 10(6.3) 50%
      embryo infectious dose/bird of A/ chicken/Iran/SH-110/99 (H9N2) virus via nasal
      inoculation. Clinical signs such as depression, ruffled feathers, diarrhea, and
      nasal and eye discharges were observed 6 days postinfection (PI). No mortality
      was observed; however, there was reduction in feed and water consumption and egg
      production. However, the serologic response of vaccinated challenged and
      unvaccinated challenged birds was not significantly different. Unvaccinated
      challenged quail showed more severe histopathologic reaction in their lungs and
      trachea. Hyperemia, edema, infiltration of inflammatory cells, and deciliation
      and sloughing of the tracheal epithelium were observed. Ultrastructural study
      showed dilatation of endoplasmic reticulum and degeneration of Golgi apparatus
      and cilia of the tracheal lining cells of respiratory epithelium.

PMID- 17494592
TI  - Development of a reverse genetics system enabling the rescue of recombinant avian
      influenza virus A/Turkey/England/50-92/91 (H5N1).
AB  - We previously described the use of an established reverse genetics system for the
      generation of recombinant human influenza A viruses from cloned cDNAs. Here, we
      have assembled a set of plasmids to allow recovery of the avian H5N1 influenza
      virus A/Turkey/England/50-92/91 entirely from cDNA. This system enables us to
      introduce mutations or truncations into the cDNAs to create mutant viruses
      altered specifically in a chosen gene. These mutant viruses can then be used in
      future pathogenesis studies in chickens and in studies to understand the host
      range restrictions of avian influenza viruses in humans.

PMID- 17494593
TI  - Induced increase in virulence of low virulence highly [corrected] pathogenic
      avian influenza by serial intracerebral passage in chickens.
AB  - Two highly pathogenic avian influenza (HPAI) virus clones that met the criteria
      for high-pathogenicity avian influenza viruses, by possessing a multibasic
      hemagglutinin (HA) cleavage site, were isolated from an H5N1 outbreak in Norfolk,
      England, in 1991-92. These two isolates, A/turkey/England/50-92/91 (50-92) and
      A/turkey/England/87-92/91 (87-92), displayed differences in virulence as
      determined by intravenous pathogenicity index-3 and -0, respectively. DNA
      sequencing of these two isolates identified 10 amino acid differences throughout
      the genome: three in HA and polymerase B2 (PB2) and two in polymerase B1 (PB1)
      and single mutations in nucleoprotein (NP) and polymerase A (PA). Serial
      intracerebral passages were performed in 1- or 2-day-old specific pathogen free
      (SPF) chicks with 87-92. Viruses reisolated from each bird passage displayed
      increases in intracerebral pathogenicity index values (from 0 to 1.9) and
      therefore virulence. Reverse transcriptase polymerase chain reaction and DNA
      sequencing on viruses isolated at each passage displayed nine out of the 10
      mutations associated with the higher pathogenic genotype of 50-92, except for the
      mutation found in NP, which retained the amino acid residue associated with 87
      92. Serial passage through 9-day-old SPF embryonated chicken eggs and serial
      intravenous passage in 6-wk-old birds could not reproduce these results. These
      results further highlight that nucleotide changes in the genome other than at the
      HA cleavage site can attenuate the virulence of HPAI viruses.

PMID- 17494594
TI  - Lethality and molecular characterization of an HPAI H5N1 virus isolated from
      eagles smuggled from Thailand into Europe.
AB  - On October 18, 2004, two crested hawk eagles, Spizaetus nipalensis, smuggled into
      Europe from Thailand were seized at Brussels International Airport. A highly
      pathogenic avian influenza virus, denominated A/crested eagle/Belgium/01/2004,
      was isolated from these birds and antigenically characterized as H5N1. Here we
      report on the molecular characterization of A/crested eagle/Belgium/01/2004
      (H5N1). We completely sequenced all eight genome segments. The hemagglutinin (HA)
      and neuraminidase (NA) sequences clustered within the Z genotype and were closely
      related to strains circulating in Thailand during 2004, although some mutations
      in the HA were evident, notably a unique arginine (R) > lysine (K) replacement in
      the cleaving site. The HA cleavage site contained six basic amino acids,
      confirming its high pathogenicity (intravenous pathogenicity index = 2.94). The
      20-amino acid deletion in the NA stalk region is consistent with its Thai-Viet
      origin. We further discuss the assembled genetic information in the light of
      currently known host adaptation, virulence, and antiviral resistance factors.
      Using infection experiments, we show that pathogenicity in chickens depends on
      breed, inoculation route (oculonasal vs. intramuscular), and dose. Additionally,
      in Muscovy ducks, pathogenicity proved to be age dependent.

PMID- 17494596
TI  - Influenza virus surveillance in wild birds in Italy: results of laboratory
      investigations in 2003-2005.
AB  - Following the avian influenza (AI) epidemics occurring in different areas of the
      world, a surveillance program funded by the Italian Ministry of Health was
      implemented. In the framework of this program, an investigation of wild birds was
      carried out to assess the circulation of AI viruses in their natural reservoir.
      More than 3000 samples, mainly cloacal swabs, were collected from migratory wild
      birds belonging to the orders Anseriformes and Charadriiformes. Samples were
      screened by means of a real-time reverse transcriptase polymerase chain reaction
      (RRT-PCR), then processed for attempted virus isolation in embryonated fowl's
      specific pathogen-free eggs. Approximately 5% of the samples were positive for
      type A influenza viruses by RRT-PCR, and from 14 of those samples AI viruses were
      isolated and fully characterized. The isolates, belonging to 8 different avian
      influenza virus subtype combinations (H10N4, H1N1, H4N6, H7N7, H7N4, H5N1, H5N2,
      and H5N3), were obtained from migratory Anseriformes.

PMID- 17494595
TI  - Virologic findings in selected free-range mule duck farms at high risk for avian
      influenza infection.
AB  - Prevalence of avian influenza infection in free-range mule ducks (a cross between
      Muscovy [Cairina moschata domesticus] and Pekin ducks [Anas platyrhychos
      domesticus]) is a matter of concern and deserves particular attention. Thus,
      cloacal swabs were collected blindly from 30 targeted mule flocks at 4, 8, and 12
      wk of age between October 2004 and January 2005. They were stored until
      selection. On the basis of a positive H5 antibody detection at 12 wk of age with
      the use of four H5 antigens, the samples from eight flocks were selectively
      analyzed. Positive samples were first screened with a matrix gene-based real-time
      reverse transcriptase-polymerase chain reaction assay before virus isolation.
      Eight avian influenza subtypes (H5N1, H5N2, H5N3, H6N2, H6N8, and H11N9) and
      three avian paramyxovirus type 1 viruses were isolated. All 11 are characterized
      as low pathogenicity (LP) and avirulent, respectively, by in vivo tests and, when
      relevant, nucleotide sequencing of the hemagglutinin (or fusion [F]) protein
      cleavage site. Regarding H5 isolates, all of their eight genes belong to the
      avian lineage and some particular genetic traits were determined. H5 genes were
      fully sequenced and phylogenetically analyzed; they all belong to the Eurasian
      lineage, lack additional glycosylation sites, and do not cluster, suggesting
      separate introductions from the wild reservoir. None were grouped with the Asian
      isolates. The N1 gene (H5N1 isolate) was very close genetically to an Italian LP
      H7N1 gene. Antigenic relationships between these H5 isolates and others were
      assessed comparatively by crossed hemagglutination inhibition tests. All these
      data are very useful to control the evolution of H5 viruses at the genetic and
      antigenic level to better understand the source of new outbreaks (new
      introductions from wild birds or the result of spread among poultry) and to
      assess the immunity afforded by available vaccines. These data are useful also to
      update antigens for avian influenza survey and to choose the most suitable
      vaccine in the case of preventive vaccination of ducks.

PMID- 17494597
TI  - Description of live poultry markets in the United States and factors associated
      with repeated presence of H5/H7 low-pathogenicity avian influenza virus.
AB  - In 2005 the National Animal Health Monitoring System conducted a survey in 183
      live poultry markets throughout the United States. The objectives of this study
      were to describe characteristics of live poultry markets in the United States and
      to identify potential risk factors for markets to be repeatedly positive for low
      pathogenicity avian influenza virus (LPAIV) H5/H7. A questionnaire was
      administered to market operators that included questions regarding types of birds
      and other animals in the market, biosecurity, and cleaning and disinfecting
      practices. A history of testing for avian influenza from March 2004 through March
      2005 was obtained for each market. Cases were defined as markets with at least 2
      positive LPAI/H5/H7 test results during the year (separate occasions), and
      controls were defined as markets that were tested at least twice during the year
      with all negative results. Markets in the North region (New York, New Jersey,
      Pennsylvania, New England) were larger than markets in the South (Florida,
      California, Texas) and were more likely to slaughter birds on-site. Testing for
      avian influenza virus (AIV) was performed more frequently in the North region
      than in the South region. Markets in the North region tested positive for H5 or
      H7 at 14.6% of the testing visits, and no markets in the South region tested
      positive for H5/H7 at any time during the year. Factors associated with repeated
      presence of LPAIV H5/H7 included number of times the market was cleaned and
      disinfected, being open 7 days per week, and trash disposal of dead birds.

PMID- 17494598
TI  - Spatial analysis of the 1999-2000 highly pathogenic avian influenza (H7N1)
      epidemic in northern Italy.
AB  - The effect of proximity on infected premises was evaluated during the highly
      pathogenic avian influenza (HPAI) epidemic that struck northern Italy in 1999
      2000 by quantifying the spatial and temporal clustering of cases. The epidemic
      was caused by an H7N1 subtype of type A influenza virus that originated from a
      low-pathogenic AI virus that spread among poultry farms in northeastern Italy in
      1999 and eventually became virulent by mutation. More than 90% of 413 infected
      premises were located in Lombardy and Veneto regions; of 382 outbreaks, 60%
      occurred in the Lombardy region and 40% in the Veneto region. Global and local
      spatial statistics were used to estimate the location and degree of clustering of
      cases with respect to the population at risk. Outbreaks were spatially clustered
      primarily in Lombardy, with a large cluster in Brescia province and another in
      Mantua province, on the border of Veneto. Time series analysis was used to assess
      the temporal clustering of outbreaks. Temporal aggregation increased during the
      first 5 wk and decreased thereafter (probably as a result of eradication measures
      enforced in the Veneto region). Spatio-temporal clustering was assessed
      considering the Temporal Risk Window (TRW), the time period during which premises
      remain infectious and infection can spread to neighboring premises. The
      clustering pattern was similar to the one detected when considering spatial
      clustering (i.e., the larger clusters were identified in the Brescia and Mantua
      provinces of Lombardy). These results highlight the role of proximity in the
      spread of AI virus and, when considering the TRW, indicate the possible direction
      of virus spread.

PMID- 17494599
TI  - Avian influenza virus screening in wild waterfowl in Norway, 2005.
AB  - The prevalence of influenza A virus infection, and the distribution of different
      subtypes of the virus, were studied in 604 geese and ducks shot during ordinary
      hunting 2005. The study was based upon molecular screening of cloacal swabs taken
      by the hunters. The sampling included the following species: greylag (Anser
      anser), mallard (Anas platyrhynchos), wigeon (Anas penelope), teal (Anas crecca),
      goosander (Mergus merganser), tufted duck (Aythya fuligula), common scoter
      (Melanitta nigra), goldeneye (Bucephala clangula), and red-breasted merganser
      (Mergus serrator). The samples found to be positive in the initial pan-influenza
      A virus reverse transcription-polymerase chain reaction (RT-PCR) were further
      subtyped by using a specific H5 RT-PCR and full-length RT-PCRs for the
      hemagglutinin (HA) and neuraminidase genes. None of the greylag samples (0/185)
      were positive for influenza Avirus, whereas 19.1% of the ducks (80/419) were
      positive. The prevalences of influenza A virus in the different duck species were
      as follows: mallard, 20.4% (58/284); wigeon, 12.5% (8/64); teal, 30.9% (13/42);
      goosander, 0% (0/5); tufted duck, 0% (0/4); common scoter, 14.3% (1/7);
      goldeneye, 0% (0/11); and red-breasted merganser, 0% (0/2). H5N1 subtype was
      found in one mallard and H5N2 subtype in another mallard and one teal. Sequencing
      of the HA gene identified all three viruses as low-pathogenic strains, closely
      related to low-pathogenic H5 influenza A viruses evidenced in recent years in
      Sweden and the Netherlands. The other subtypes identified included H1N1, H2,
      H3N2, H3N8, H6N1, H6N2, H6N8, H8N4, H9N2, H11N9, and H12 in mallards; H3N2, H6N2,
      H6N8, and H9N2 in teals; and H6N2 in wigeons and common scoter.

PMID- 17494600
TI  - Relationship between H5N2 avian influenza viruses isolated from wild and domestic
      ducks in British Columbia, Canada.
AB  - In the summer of 2005 a Canadian national surveillance program for influenza A
      viruses in wild aquatic birds was initiated. The program involved collaboration
      between federal and provincial levels of government and was coordinated by the
      Canadian Cooperative Wildlife Health Centre. The surveillance plan targeted young
      of-the-year Mallards along with other duck species at six sampling locations
      along the major migratory flyways across Canada. Beginning in early August,
      cloacal swabs were taken from 704 ducks on two lakes adjacent to one another near
      Kamloops, British Columbia. The swabs were screened for the presence of influenza
      A RNA using a real-time reverse transcription-polymerase chain reaction (RRT-PCR)
      assay that targets the M1 gene. Swab samples that gave positive results underwent
      further testing using H5- and H7-specific RRT-PCR assays. One hundred and seventy
      four cloacal swab specimens gave positive or suspicious results for the presence
      of an H5 virus. A portion of these (28/35) were confirmed using an H5-specific
      conventional reverse transcription-polymerase chain reaction assay and an H5
      virus was eventually isolated from 24/127 swab specimens. Neuraminidase typing
      revealed the presence of H5N2 and H5N9 viruses. In mid-November of 2005 an H5N2
      virus was detected in a commercial duck operation in the lower mainland of
      British Columbia, approximately 120 km from where the H5N2-positive wild ducks
      were sampled. Molecular genetic analysis of the H5N2 viruses isolated from wild
      and domestic ducks was carried out to determine their kinship.

PMID- 17494601
TI  - Investigations on infection status with H5 and H7 avian influenza virus in short
      distance and long-distance migrant birds in 2001.
AB  - The role of migrating birds as potential vectors for avian influenza virus (AIV)
      was investigated. We captured 543 migrating passerines during their stopover on
      the island of Helgoland (North Sea) in spring and autumn 2001. These birds were
      sampled for avian influenza A viruses (AIV), specifically the subtypes H5 and H7.
      For virus detection, samples were taken from 1) short-distance migrants, such as
      chaffinches (Fringilla coelebs; n = 131) and song thrushes (Turdus philomelos; n
      = 169); and 2) long-distance migrants, such as garden warblers (Sylvia borin; n =
      142) and common redstarts (Phoenicurus phoenicurus; n = 101). Virus isolation
      assays failed to identify AIV. Therefore, regarding the actual low number of
      samples, we speculate that the tested four species of passerines were not
      infected by AIV, indicating that the passerine species examined in this study may
      play only a minor role as potential vectors of AIV.

PMID- 17494602
TI  - Computational identification of reassortments in avian influenza viruses.
AB  - The avian influenza virus (AIV) has eight genomic segments (hemagglutinin [HA],
      neuraminidase [NA], RNA polymerase subunit A [PA], RNA polymerase subunit B1
      [PB1], RNA polymerase subunit B2 [PB2], nucleoprotein [NP], nonstructural gene
      [NS], and matrix protein [M]). The genetic reassortments, recombinations, and
      mutations lead to a rapid emergence of novel genotypes of the AIVs during their
      evolution. These emerging viruses provide a large reservoir for pandemic strains.
      Here we describe a novel computational strategy for genetic reassortment
      identification. In contrast to the traditional phylogenetic approaches, our
      method views the genotypes through the modules in networks. Genetic segments with
      short phylogenetic distance are grouped into modules. Our method is not limited
      to the number of sequences. We applied this method in reassortment identification
      of NP segments in H5N1 AIVs. We identified two new potential reassortments for
      H5N1 AIVs beyond the reported genotypes in literature.

PMID- 17494603
TI  - The role of wild birds in the spread of HPAI H5N1.
AB  - There is much debate about the relative roles of poultry movements and wild bird
      movements in the spread of highly pathogenic avian influenza H5N1. This article
      looks at the problem from an ornithologic perspective. Outbreaks in wild birds
      are examined in relation to three scenarios of possible wild bird involvement in
      virus transmission. These scenarios are examined separately for five phases of
      the outbreak that began in 1997 and which has recently become more dynamic in
      terms of virus spread. Most outbreaks in wild birds seem to reflect local
      acquisition of infection from a contaminated source, followed by rapid death
      nearby. Outbreaks in Europe in early 2006 indicate that the virus can be spread
      further by wild birds and thus that they can become infected and travel varying
      distances before dying, and probably passing the infection to other wild birds
      before death. There is only limited evidence that some wild birds can carry the
      virus asymptomatically, and no evidence from wild bird outbreaks that they have
      done so over long distances on seasonal migration routes. Other potential sources
      of infection and evidence for asymptomatic infection in wild birds are discussed,
      and the need for more ornithologic input into epidemiological studies of HPAI
      H5N1 is highlighted.

PMID- 17494604
TI  - Molecular epidemiologic studies on North American H9 avian influenza virus
      isolates from waterfowl and shorebirds.
AB  - Because sequence data on H9 avian influenza virus (AIV) from wild birds are
      currently limited, we set out to determine the sequence of the hemagglutinin (HA)
      gene of H9 viruses circulating in North American waterfowl and shorebirds. In
      this study, we examined the HA gene from H9 AIV isolated from mallards (Anas
      platyrhynchos) sampled during 1998 and 1999 in Minnesota and ruddy turnstones
      (Arenaria interpres) sampled during 2003 in Delaware and New Jersey. At these
      sites, the H9N2 subtype represented 12% and 4% of the avian influenza isolates
      from mallards in 1998 and 1999, respectively, and 8% of the AIVs isolated from
      shorebirds between 2000 and 2002. Sequences from these viruses were compared with
      sequences from H9 AIV isolated from commercial poultry and aquatic birds from
      North America, Europe, Asia, and the Middle East: four previously reported and
      three new clades were observed. Sequence data from the HA gene of North American
      waterfowl and shorebird isolates generated in this study most closely group with
      the Eurasian H9 viruses in the Y439 clade. In addition, the HA cleavage site
      (AASNR/G) and receptor binding site was identical to the representative virus of
      that group (DK/Hong Kong/Y439/97). Viruses in that clade are commonly found in
      ducks and chickens in Hong Kong and Korea. Positive evolutionary selection
      (dNonsynonymous > dSynonymous) was observed for the HA gene among the North
      American waterfowl and shorebird H9N2 viruses, indicating that the H9N2-type
      viruses are changing in their natural hosts.

PMID- 17494605
TI  - Genetic comparison of H9N2 AI viruses isolated in Jordan in 2003.
AB  - SUMMARY. During the 1990s, several outbreaks of avian influenza (AI), caused by
      viruses of the H9N2 subtype, were reported in poultry in various parts of the
      world. Currently, this infection seems to be endemic in poultry in the Middle and
      Far East, and the extensive circulation of H9N2 in poultry represents a risk
      factor for infection of humans, because viruses of this subtype have been
      sporadically introduced into the human population. Little is known about the gene
      constellation of the H9N2 viruses that are currently circulating in the Middle
      East; thus, gene sequences of eight IA viruses of the H9N2 subtype isolated in
      Jordan in 2003 from poultry were analyzed. The results of this investigation show
      that all eight Jordanian isolates are closely related to each other and to other
      H9N2 isolates from the Middle East. Seven of eight genes of the Jordanian strains
      show a percentage of homology not higher than 95% with the genes of two H9N2
      strains, A/HK/1073/99 and A/HK/1074/99, isolated from humans in Hong Kong. The M
      gene is more closely related to the corresponding gene of the two H9N2 human
      isolates from Hong Kong (97.7-98.2% homology). This homology suggests that the M
      gene of the Jordanian and human Hong Kong strains could derive from a common
      ancestor.

PMID- 17494606
TI  - Evolutionary analysis of HA and NS1 genes of H5N1 influenza viruses in 2004-2005
      epidemics.
AB  - H5N1 avian influenza viruses circulating in early 2004 in eastern Asia appeared
      to be under strong purifying selection, except for the hemagglutinin (HA) and
      nonstructural 1 (NS1) genes, where few amino acid positions were found under
      positive selection pressure. To evaluate whether the widespread circulation of
      the H5N1 viruses in the following years was accompanied by a change in the
      evolution of the HA and NS1, phylogenetic and positive selection analyses were
      performed on 89 HA and 57 NS1 sequences. Results showed that the number of HA
      positively selected sites decreased compared to 2004; no selection pressure for
      NS1 was found. These findings suggest a possible change in the adaptation of the
      H5N1 virus to birds.

PMID- 17494607
TI  - Practical problems in controlling H5N1 high pathogenicity avian influenza at
      village level in Vietnam and introduction of biosecurity measures.
AB  - After a consultancy mission funded by a nongovernmental organization (NGO),
      information was collected on the dynamics of avian influenza (AI) infection at
      the rural level in a Vietnamese province with several ongoing outbreaks. AI
      outbreaks are frequent at village level due to environmental, ecological,
      agroecological, physical, social, and cultural factors, the underlying factor
      being poor hygienic conditions. Viral circulation is facilitated by the
      interactions of the integrated aquaculture, animal raising, horticulture
      agroecosystem, which relies in the peculiar integration of aquaculture (ponding),
      animal activities, and horticulture and by the connections with the live-bird
      market system. The interactions of these factors determine the complex system in
      which wild birds interact with domestic birds and in which people are constantly
      exposed to sources of infection, leading to the association between poverty and
      AI infection in humans. This experience underlines that despite all efforts by
      the Vietnamese Government, international institutions, and the NGO sector,
      awareness of AI at the village level needs to be improved. In turn, the leading
      institutions and international donors funding projects of technical cooperation
      aimed at tackling AI in Vietnam should invest in a system based on a deep
      knowledge of the practical problems of village condition to address AI with an
      effective approach. On the basis of the data collected during the mission,
      particularly on rural and semi-intensive poultry rearing systems, proposals that
      encompass the application of an effective vaccination strategy including backyard
      flocks coupled with dissemination of relevant information on biosecurity measures
      have been developed for decision makers.

PMID- 17494608
TI  - Evaluation of the efficacy of intervention measures and vaccination for the
      control of LPAI epidemics in Verona province (Veneto, Italy).
AB  - Meat-type turkey farms in Verona province (Veneto, Italy) have been affected by
      three low-pathogenicity avian influenza (LPAI) epidemics between 2000 and 2004.
      Control measures implemented ranged from stamping out to controlled marketing in
      conjunction with restocking bans and movement restriction on live poultry,
      vehicles, and personnel. These measures were complemented with two emergency
      vaccination programs (2000-01, 2002-03) started after the beginning of the
      epidemics, while 2004 outbreaks occurred in vaccinated farms. The three epidemics
      differed in the number of outbreaks, duration, and economic impact. The aim of
      the investigation was to estimate the risk of infection and the effect of
      vaccination on the LPAI epidemics affecting turkey farms in Verona province. Farm
      probability to avoid infection (Ps) was calculated by Kaplan-Meier for each
      epidemic. The vaccination effect was evaluated for the 2000-01 and 2002-03
      epidemics considering different risk before or after the emergency vaccination.
      The epidemics and vaccination entered as predictors in a Cox regression model and
      hazard ratios (HR) were calculated. Ps values at the end of the epidemics were as
      follows: 2000-01 = 0.66, 2002-03 = 0.51, and 2004 = 0.91. Vaccination reduced
      dramatically the risk of infection. The measures implemented had different
      effects on the three epidemics. The lower probability of being infected during
      the 2004 epidemic was most likely related to the protection level of the
      vaccinated farms acquired before the beginning of the epidemic, which was also
      responsible for the reduced spread of infection.

PMID- 17494609
TI  - Avian influenza surveillance in backyard poultry of Argentina.
AB  - Avian influenza (AI) is an exotic disease in Argentina. A surveillance program
      for AI was conducted in backyard poultry during 1998-2005 in two regions: 1)
      region A, which included the avian population in the provinces that border
      Brazil, Bolivia, and Paraguay, and 2) region B, which included the rest of the
      provinces of the country. More than 8000 serum samples were tested for antibodies
      by enzyme-linked immunosorbent assay and/or agar gel immunodiffusion tests, and
      more than 18,000 tracheal and cloacal swabs were tested for virus by isolation in
      embryonated specific-pathogen-free eggs. This study was part of the AI prevention
      program in Argentina, which includes other avian populations such as commercial
      poultry and all the controls for importation and exportation of live birds. The
      results from backyard poultry were negative for AI.

PMID- 17494610
TI  - Intervention strategies for low-pathogenic avian influenza control in Italy.
AB  - Italian poultry production was affected by several outbreaks of low-pathogenicity
      avian influenza (LPAI) between 2000 and 2005. Intervention measures (IM), such as
      stamping out of infected and suspected farms, controlled marketing, restocking
      bans, movement restriction, and emergency vaccination, were put into force in the
      most affected areas of Lombardia and Veneto regions. These two regions also
      showed differences in terms of measures applied and timeliness of application. In
      this study we describe the epidemics and discuss the effectiveness of the IM put
      into effect. The regional surveillance systems provided the data on the epidemics
      and the IM description. The IM effectiveness was compared between the different
      epidemics and the Lombardia and Veneto regions, considering the number of farms
      involved, the duration of the epidemics, and the extension of the area affected.
      With regard to the IM applied, reductions in the number of outbreaks (from 388 in
      2002-03 to 15 in 2005), the duration of the outbreaks (from more than 1 yr to
      approximately 1 mo), and the spatial extension of the outbreaks (from 89 to 8
      municipalities involved) were observed. The emergency vaccination, depopulation,
      and pre-emptive slaughtering reduced significantly the spread of the epidemic.
      Comparing the dynamics of the epidemics, more effective results were observed in
      the Veneto region, where the IM were applied to a greater extent. Emergency
      vaccination and depopulation were effective in the eradication of the disease
      during an epidemic, but vaccination and farm density reduction showed the most
      effective results in controlling the spread of LPAI.

PMID- 17494611
TI  - Characterization of H5N2 influenza A viruses isolated from chickens in Japan.
AB  - A low pathogenic avian influenza virus of the H5N2 subtype was isolated for the
      first time from layer chickens in Japan in 2005. Surveillance in trading
      restriction zones and epidemiologically related farms revealed 41 seropositive
      farms, and 16 H5N2 viruses were isolated and characterized from nine of these
      farms. That these viruses were genetically and antigenically similar to each
      other suggested that these isolates were derived from a common origin. Complete
      genomic characterization of all eight gene segments showed that these H5N2
      isolates in Japan had high homology to the H5N2 strains prevalent in Central
      America since 1994. The virus was reisolated from tracheal and cloacal swabs of
      experimentally inoculated chickens and efficiently transmitted to sentinel
      chickens in adjacent cages.

PMID- 17494612
TI  - Effects of homologous and heterologous neuraminidase vaccines in chickens against
      H5N1 highly pathogenic avian influenza.
AB  - The 2004 Asian H5N1 epizootic outbreak indicates the urgent need for vaccines
      against highly pathogenic avian influenza (HPAI) virus. The manufacture of
      inactivated whole-virus vaccines from HPAI viruses by traditional methods is not
      feasible for safety reasons as well as technical issues. The low pathogenic avian
      influenza A/wild bird feces/CSM2/02 (H5N3) virus was used as a heterologous
      neuraminidase vaccine, and HPAI A/CK/Korea/ES/03 (H5N1) virus was used as a
      homologous neuraminidase vaccine. Protection efficacy of both vaccines was
      evaluated by clinical signs, mortality rates, and virus shedding from oropharynx
      and cloaca of vaccinated chickens after challenge with HPAI A/CK/Korea/ES/03
      (H5N1) virus. One dose of 128 hemagglutinin (HA) homologous H5N1 vaccine induced
      100% protection in mortality and prevented viral shedding completely after lethal
      dose virus challenge, whereas one dose of 64 HA unit of heterologous H5N3 vaccine
      only induced 50% protection in mortality, and it did not prevent viral shedding.
      However, two doses at a 3-wk interval of 64 HA unit of heterologous H5N3 vaccine
      as well as one dose of 1024 HA unit of heterologous H5N3 vaccine induced 100%
      survival rate and could prevent viral shedding completely. Furthermore, we could
      differentiate the sera of infected birds from those of vaccinated birds by
      indirect immunofluorescent antibody test. These results suggest that heterologous
      neuraminidase H5N3 vaccine could be a useful tool for the control of H5N1 HPAI
      epidemic in poultry.

PMID- 17494613
TI  - Generation of avian influenza reassortant viruses of the H7N5 subtype as
      potential vaccine candidates to be used in the framework of a "DIVA" vaccination
      strategy.
AB  - The recent outbreaks of avian influenza (AI) worldwide have highlighted the
      difficulties in controlling this disease. Vaccination has become a recommended
      tool to support the eradication efforts and to limit the economic losses due to
      AI. A vaccination system based on the use of a vaccine containing a heterologous
      neuraminidase to the field virus has been shown to be efficacious in reducing the
      viral shedding and clinical symptoms and in differentiating vaccinated from
      infected animals. To further develop this so called differentiating infected from
      vaccinated animal vaccination system, two reassortant avian influenza viruses of
      the H7N5 subtype have been generated. The aim of this study was to generate a
      prototype strain with a rare N subtype to avoid interference with the anti-N
      discriminatory test.

PMID- 17494614
TI  - Association of serologic and protective responses of avian influenza vaccines in
      chickens.
AB  - A study was conducted to evaluate efficacy of inactivated, reverse genetics-based
      H5N3 avian influenza vaccines and the predictive ability of a
      vaccination/serology model for testing vaccine batches. Serologic response,
      protection against mortality, and protection against viral shedding from trachea
      and cloaca were assessed for vaccines prepared varying only in antigen content.
      When the birds were grouped according to serologic response, a clear association
      with protection could be seen. In general, for birds possessing a nonmeasurable
      titer (< 10), mortality after challenge was a near certainty. Low titers of 10 to
      40 resulted in the prevention of mortality but not viral shedding. Titers greater
      than 40 prevented mortality and reduced viral shedding. The results suggest that
      a test model including vaccination of chickens at 3 wk, bleeding at 6 wk, and
      quantitative assessment of serologic response by using a standardized
      hemagglutination inhibition assay system can be an excellent predictor of vaccine
      efficacy.

PMID- 17494615
TI  - Assessment of the protection afforded by triple baculovirus recombinant
      coexpressing H5, N3, M1 proteins against a homologous H5N3 low-pathogenicity
      avian influenza virus challenge in Muscovy ducks.
AB  - In Asia, domestic ducks have been shown to play a pivotal role in H5 high
      pathogenicity avian influenza virus transmission. We have also observed that the
      same situation may exist for H5 low-pathogenicity avian influenza (LPAI) virus.
      No data are available regarding the protection afforded by commercial inactivated
      vaccines against H5 LPAI virus infection in ducks, and two preliminary
      experiments using commercial inactivated vaccines gave poor results. Virus-like
      particles (VLPs) have been shown to be immunogenic in different species. With
      regard to the influenza model, the matrix (M) protein has been shown to be
      necessary for the formation of VLPs. In order to attempt to develop a VLP
      influenza vaccine expressing hemagglutinin and neuraminidase (NA) of interest, we
      generated a triple recombinant baculovirus (rB) expressing three structural
      proteins: H5, N3, and M, derived from a recent French LPAI virus strain. Although
      the three proteins were successfully expressed in rB-infected cells and displayed
      the expected biological activity, no VLPs were observed. Despite this result, the
      protection afforded to ducks by rB-infected cell lysates was assessed and was
      compared with the protection afforded by an inactivated commercial H5N9 vaccine.
      For this purpose, specific-pathogen-free Muscovy ducks (15 per group) received rB
      infected cell lysates (3 wk apart), while a second group received the H5N9
      vaccine. Ten days after the boost, a homologous virus challenge was implemented.
      Both vaccines induced positive hemagglutination inhibition titers and M immune
      response, whereas lysates of rB-infected cells elicited NA immune response.
      Tracheal and cloacal sheddings were measured using M-based real-time-reverse
      transcription-polymerase chain reaction and were compared with the sheddings of
      vaccinated and unvaccinated infected controls. Lysates of rB-infected cells
      afforded a significant decrease of cloacal shedding and a delayed peak of
      tracheal shedding, whereas the inactivated commercial vaccine afforded a
      significant decrease of tracheal shedding only.

PMID- 17494616
TI  - Importance of a prime-boost DNA/protein vaccination to protect chickens against
      low-pathogenic H7 avian influenza infection.
AB  - Control of H5/H7 low-pathogenic avian influenza (LPAI) virus circulation is a
      major issue regarding animal and public health consequences. To improve vaccines
      and to prevent vaccinated poultry from becoming infected and from shedding wild
      viruses, we initiated studies targeting prevention of H7 infection through DNA
      vaccines encoding H7 and M1 viral proteins from an Italian H7N1 LPAI virus
      isolated from poultry in 1999. More recently, we expressed recombinant H7 and M1
      proteins in the baculovirus system to assess whether they might enhance immunity
      when given as a boost after DNA vaccination. The protection afforded by three
      vaccine combinations-DNA/DNA, DNA/protein, protein/protein-given 3 wk apart were
      experimentally compared in 20 specific-pathogen-free chickens per group. Ten days
      after the boost, chickens were challenged with a homologous (Italian H7N1 LPAI)
      or heterologous (French H7N1 LPAI isolated from mallards in 2001) virus. Tracheal
      and cloacal shedding was measured by a matrix gene (M)-based real-time reverse
      transcription polymerase chain reaction assay and compared with that displayed by
      unvaccinated infected controls. After the homologous challenge, chickens of every
      vaccinated group displayed a significant decrease in cloacal shedding, whereas
      tracheal shedding was not significantly reduced in the protein/protein group.
      After the heterologous challenge, only the DNA/DNA group showed a nonsignificant
      decrease in tracheal shedding. According to these two trials, prime-boost
      DNA/protein vaccination appeared be more advantageous. Further development could
      be aimed at improving protein expression, shifting subtype (H5), and assessing
      the interest of proteins as a boost of recombinant vaccines.

PMID- 17494617
TI  - Conventional H5N9 vaccine suppresses shedding in specific-pathogen-free birds
      challenged with HPAI H5N1 A/chicken/Yamaguchi/7/2004.
AB  - Avian influenza represents one of the greatest concerns for public health that
      has emerged in recent times. Highly pathogenic avian influenza viruses belonging
      to the H5N1 subtype are endemic in Asia and are spreading in Europe and Africa.
      Vaccination is now considered a tool to support eradication efforts, provided it
      is appropriately managed. This study was carried out to establish the degree of
      clinical protection and reduction of viral shedding induced by a high
      specification, commercially available avian influenza vaccine of a different
      lineage and containing a strain with a heterologous neuraminidase (H5N9 subtype)
      to the challenge virus isolate A/chicken/Yamaguchi/7/2004 (H5N1 subtype).

PMID- 17494618
TI  - Efficacy of a fowlpox-vectored avian influenza H5 vaccine against Asian H5N1
      highly pathogenic avian influenza virus challenge.
AB  - A recombinant fowlpox-avian influenza (AI) H5 vaccine (rFP-AIV-HS) expressing the
      hemagglutinin of the A/turkey/Ireland/1378/83 H5N8 AI isolate has been used in
      Central America since 1998 to control H5N2 low pathogenicity AI. Previously, this
      vaccine was shown to induce full protection against a panel of H5 highly
      pathogenic (HP) AI isolates, including HPAI H5N1. Here, we evaluate the efficacy
      of rFP-AIV-H5 against escalating doses of HPAI H5N1 A/chicken/ SouthKorea/ES/03
      isolate and against the HPAI H5N1 A/chicken/Vietnam/0008/2004 isolate. In both
      studies, 1-day-old specific pathogen-free (SPF) chickens were vaccinated by
      subcutaneous route with rFP-AIV-H5 and challenged 3 wk later by the oronasal
      route. In the first study, full protection was observed up to a challenge dose of
      6.5 log10 embryo infectious dose (EID50), and the 50% chicken infectious dose was
      estimated to be 3.1 and 8.5 log10 EID50 in the control and the rFP-AIV-H5
      vaccinated group, respectively. A 2-4 log10 and > 4 log10 reduction of oral and
      cloacal shedding was observed in rFP-AIV-H5 vaccinated birds, respectively. The
      rFP-AIV-H5 vaccine induced hemagglutination inhibition antibodies (5.2 log2)
      detectable with homologous H5N8 antigen. In the second study, rFP-AIV-HS
      vaccinated chicks were fully protected against morbidity and mortality after
      challenge with the 2004 Vietnam isolate, whereas unvaccinated chickens died
      within 2 days of challenge. Shedding in cloacal swabs was detected in all
      unvaccinated controls but in none of the rFP-AIV-H5-vaccinated chickens.
      Together, these results confirm the excellent level of protection induced by rFP
      AIV-H5 in SPF chickens against two recent Asian HPAI H5N1 isolates.

PMID- 17494619
TI  - EFSA scientific risk assessment on animal health and welfare aspects of avian
      influenza (EFSA-Q-2004-075).
AB  - Outbreaks of highly pathogenic avian influenza (HPAI) (2000-2003) resulted in 50
      million EU birds culled or dead. The circulation of H5N1 in Asia could represent
      the origin of a human pandemic. Questions have been raised to combat the ongoing
      AI crisis. HPAI H5N1 has spilled over to resident and migratory wild bird
      populations which could represent a means of the virus reaching the EU, but lack
      of data make any forecast imprudent. Poultry holdings located close to migratory
      bird breeding and resting sites are considered at greater risk of exposure and
      methods to prevent exposure should be implemented. Legal safeguards for
      importation of poultry commodities currently only apply to HPAI and rely on
      detection of clinical signs that may not be observable during incubation period.
      Illegal imports represent an additional risk. Insufficient data on the
      effectiveness of commodity processing are available and few indications can be
      deducted. Biosecurity is the primary tool to prevent AI introduction and
      secondary spread. Massive spread was observed in densely populated poultry areas
      resulting in vaccination programs. Vaccination should be used to support
      eradication together with enhanced biosecurity and restriction measures, which
      shall also be implemented in case of prophylactic vaccination. Animal welfare
      aspects of AI include use of appropriate culling methods, correct vaccine
      application, and availability of trained staff. EFSA has recently set up a new
      scientific work group to further assess the risk of HPAI introduction and spread
      posed in particular by wild, migratory birds, as well as further follow-up of
      recent AI developments.

PMID- 17494620
TI  - Conceptual framework for avian influenza risk assessment in Africa: the case of
      Ethiopia.
AB  - The avian influenza (AI) epidemic is threatening Africa mainly because the
      flyways of migratory birds link the endemic and newly infected countries with
      disease-free areas in this continent and because of the risk of introduction
      through trade. Risk analysis provides a set of tools for supporting decision
      making by the veterinary services and other stakeholders, resulting in more
      effective surveillance and emergency preparedness. The risk assessment process
      could be split into three different steps: 1) risk release through the migratory
      birds and the official and unofficial poultry-product marketing chains; 2) risk
      exposure by means of studying interfaces among imported and exposed poultry and
      among wild and domestic birds; and 3) risk consequences for establishing the
      probability of AI spreading within the poultry population and the probability of
      it escaping detection. A conceptual framework is presented based on preliminary
      data and field missions carried out in Ethiopia. Field surveys and expert opinion
      will be necessary for the parameterization of the risk model. Spatial analysis
      will be used to identify high risk of exposure among wild and domestic birds.
      Risk communication and risk management will be based on the findings from the
      risk assessment model.

PMID- 17494621
TI  - Risk assessment applied to Spain's prevention strategy against highly pathogenic
      avian influenza virus H5N1.
AB  - Notifiable avian influenza (NAI) had never been reported in Spain, until July
      2006 when a dead Great Crested Grebe (Podiceps cristatus) was found positive to
      the highly pathogenic H5N1 subtype as part of the active wild bird surveillance
      plan. The current program of the Spanish Ministry of Agriculture, Fisheries, and
      Food (MAPA)'s strategic preventive plan against NAI is divided in the following
      parts: identification of risk areas and risk wild bird species, increased
      biosecurity measures, early detection of infection with surveillance
      intensification and development of rapid diagnostic tests, and other policies,
      which include continuing education and training to ensure early detection of the
      disease. In 2003 an active surveillance plan was introduced for domestic fowl;
      the plan was extended to wild birds in 2004. A total of 18,780 samples in poultry
      and 3687 samples in wild birds had been analyzed through December 2005 to detect
      the presence and spread of avian influenza subtypes H5 and H7. In the present
      work we suggest some contributions to be implemented in MAPA's action plan: 1)
      the identification of risks because of migratory birds, within the risk
      assessment of the introduction of NAI virus in Spain and 2) an interactive
      digital simulator of the disease developed for continuing education and training.

PMID- 17494622
TI  - Variation in ribosomal RNA gene number in mouse chromosomes.
AB  - Hybridization of 125-I-ribosomal RNA to mouse chromosomes in situ produced
      significant differences in grain count at known rDNA sites, depending on the
      strains from which they were derived. This is interpreted to mean that the number
      of rRNA genes in a given nucleolar chromosome, and in the entire genome, is
      polymorphic among strains and among outbred individuals.

PMID- 17494623
TI  - Fluorescent (F) bodies in the spermatozoa of man and the great apes.
AB  - Mature spermatozoa of the chimpanzee (Pan troglodytes), the gorilla (Gorilla
      gorilla), and the orangutan (Pongo pygmaeus) were stained with quinacrine
      dihydrochloride. Fluorescent (F) bodies were visualized in the spermatozoa of the
      chimpanzee and gorilla but were absent in the orangutan, in which there is no
      brilliant fluorescence in any chromosome. The F bodies appeared to be randomly
      located in the sperm heads of these two species, as they usually are in human
      spermatozoa. However, the proportion of sperm showing one or more F bodies in the
      chimpanzee and gorilla was not comparable to what is usually found in man. The F
      bodies in the chimpanzee presumably represent brilliant regions in the autosomes,
      since the Y chromosome has no brilliant fluorescence in this species. This is
      contrary to man, in which the F body is an useful indicator of the Y chromosome.
      In the gorilla, the F bodies probably correspond to both the Y chromosome and to
      some brilliant regions in the autosomes.

PMID- 17494624
TI  - A polymorphic structural rearrangement in the chromosomes of two populations of
      orangutan.
AB  - A rearranged chromosome 9 was found in 12 of 23 specimens of orangutan, 4 of
      Bornean and 8 of Sumatran origin. Nine animals were heterozygous, and 3 were
      homozygous carriers for the variant chromosome, which was also traced in 4 other
      animals not studied by us. This type of chromosome rearrangement has been
      previously described (Seuanez et al., 1976) and is probably the same chromosome
      shown by Lucas et al. (1973) and reported by Turleau et al. (1975) in other
      specimens. There is obviously a very high incidence of this variant chromosome 9
      in Pongo pygmaeus, and it is unlikely that it could result from independent
      rearrangements occurring in unrelated specimens from two geographically isolated
      populations (Sumatran and Bornean). It is concluded that the rearrangement is of
      ancient origin and that it has been maintained in the populations of Pongo as a
      balanced polymorphism. This type of complex rearrangement resulting from two
      pericentric inversions, one inside the other, is compared with certain sporadic
      pericentric inversions in the human complement, with pericentric inversions which
      are polymorphic in other mammals, and with pericentric inversions involved in
      chromosome evolution in the Hominoidea.

PMID- 17494625
TI  - Localization of the structural genes for hexokinase-1 and inorganic
      pyrophosphatase on region (pter-->q24) of human chromosome 10.
AB  - Concordant expression of human hexokinase-1 and inorganic pyrophosphatase was
      established in somatic cell hybrids between thymidine kinase-deficient Chinese
      hamster cells and human fibroblasts carrying a translocation of the distal third
      of the long arm of chromosome 10 to chromosome 17. Neither human hexokinase-1 nor
      human inorganic pyrophosphatase expression segregated concordantly with human
      cytoplasmic glutamic-oxaloacetic transaminase expression.

PMID- 17494626
TI  - Sex-chromosome aberrations in wood lemmings (Myopus schisticolor).
AB  - The wood lemming displays certain peculiar features: (1) The sex ratio shows a
      prevalence of females (FRANK, 1966; KALELA and OKSALA, 1966), and some females
      produce only female offspring (KALELA and OKSALA, 1966). (2) In a considerable
      proportion (in the present material, slightly less than half) of the females, an
      XY chromosome complement is found in the somatic tissues, but the Y is absent in
      the germ line of those studied (Fredga et al., 1976). Therefore, (3) a mechanism
      of double nondisjunction in early fetal life of XY females has to be postulated,
      which replaces the Y in the germ line by duplication of the X. It is assumed (4)
      that the X of XY females bears a sex-reversal factor that affects the male
      determining action of the Y (Fredga et al., 1977). There is (5) a strong
      presumption that in most cases the XY females are those that produce daughters
      only, but (6) a few exceptions may occur (FRANK, unpublished observations),
      suggesting that the regulation according to assumption 3 (perhaps also to 4) is
      incomplete in XY females. In the present report, four females are described with
      a 31,XO karyotype, two females with 33,XYY or 32,XY/33,XYY, respectively, two
      males with a 33,XXY, and one male with a 32,XX/33,XXY karyotype, as observed in a
      consecutive series of 502 wood lemmings. The incidence of sex-chromosome
      anomalies in liveborn and adult animals was 2.3%; the overall incidence,
      including embryos, was 1.79%. Neither the somatic XO constitution nor the
      existence of an extra Y in females precludes fertility. However, the XXY
      condition in the male results in sterility. There is certain evidence that an
      instability of the proposed mechanism for double mitotic nondisjunction of the
      sex chromosomes in oogonia accounts for the high rate of sex-chromosome
      aberrations in wood lemmings, at least when the mother is XY.

PMID- 17494627
TI  - Oxidant-impaired intracellular Ca2+ signaling in pancreatic acinar cells: role of
      the plasma membrane Ca2+-ATPase.
AB  - Pancreatitis is an inflammatory disease of pancreatic acinar cells whereby
      intracellular calcium concentration ([Ca(2+)](i)) signaling and enzyme secretion
      are impaired. Increased oxidative stress has been suggested to mediate the
      associated cell injury. The present study tested the effects of the oxidant,
      hydrogen peroxide, on [Ca(2+)](i) signaling in rat pancreatic acinar cells by
      simultaneously imaging fura-2, to measure [Ca(2+)](i), and dichlorofluorescein,
      to measure oxidative stress. Millimolar concentrations of hydrogen peroxide
      increased cellular oxidative stress and irreversibly increased [Ca(2+)](i), which
      was sensitive to antioxidants and removal of external Ca(2+), and ultimately led
      to cell lysis. Responses were also abolished by pretreatment with
      (sarco)endoplasmic reticulum Ca(2+)-ATPase inhibitors, unless cells were
      prestimulated with cholecystokinin to promote mitochondrial Ca(2+) uptake. This
      suggests that hydrogen peroxide promotes Ca(2+) release from the endoplasmic
      reticulum and the mitochondria and that it promotes Ca(2+) influx. Lower
      concentrations of hydrogen peroxide (10-100 muM) increased [Ca(2+)](i) and
      altered cholecystokinin-evoked [Ca(2+)](i) oscillations with marked
      heterogeneity, the severity of which was directly related to oxidative stress,
      suggesting differences in cellular antioxidant capacity. These changes in
      [Ca(2+)](i) also upregulated the activity of the plasma membrane Ca(2+)-ATPase in
      a Ca(2+)-dependent manner, whereas higher concentrations (0.1-1 mM) inactivated
      the plasma membrane Ca(2+)-ATPase. This may be important in facilitating "Ca(2+)
      overload," resulting in cell injury associated with pancreatitis.

PMID- 17494628
TI  - Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor
      antagonists.
AB  - Elevated plasma levels of cytokines such as endothelin-1 (ET-1) have been shown
      to be associated with sickle cell disease (SCD). However, the role of ET-1 in the
      pathophysiology of SCD is not entirely clear. I now show that treatment of SAD
      mice, a transgenic mouse model of SCD, with BQ-788 (0.33 mg.kg(-1).day(-1)
      intraperitoneally for 14 days), an ET-1 receptor B (ET(B)) antagonist, induced a
      significant decrease in Gardos channel activity (1.7 +/- 0.1 to 1.0 +/- 0.4
      mmol.10(13) cell(-1).h(-1), n = 3, P = 0.019) and reduced the erythrocyte density
      profile by decreasing the mean density (D(50); n = 4, P = 0.012). These effects
      were not observed in mice treated with BQ-123, an ET-1 receptor A (ET(A))
      antagonist. A mixture of both antagonists induced a similar change in density
      profile as with BQ-788 alone that was associated with an increase in mean
      cellular volume and a decrease in corpuscular hemoglobin concentration mean. I
      also observed in vitro effects of ET-1 on human sickle erythrocyte dehydration
      that was blocked by BQ-788 and a mixture of ET(B)/ET(A) antagonists but not by
      ET(A) antagonist alone. These results show that erythrocyte hydration status in
      vivo is mediated via activation of the ET(B) receptor, leading to Gardos channel
      modulation in SCD.

PMID- 17494629
TI  - S6 kinase inactivation impairs growth and translational target phosphorylation in
      muscle cells maintaining proper regulation of protein turnover.
AB  - A defect in protein turnover underlies multiple forms of cell atrophy. Since S6
      kinase (S6K)-deficient cells are small and display a blunted response to nutrient
      and growth factor availability, we have hypothesized that mutant cell atrophy may
      be triggered by a change in global protein synthesis. By using mouse genetics and
      pharmacological inhibitors targeting the mammalian target of rapamycin (mTOR)/S6K
      pathway, here we evaluate the control of translational target phosphorylation and
      protein turnover by the mTOR/S6K pathway in skeletal muscle and liver tissues.
      The phosphorylation of ribosomal protein S6 (rpS6), eukaryotic initiation factor
      4B (eIF4B), and eukaryotic elongation factor-2 (eEF2) is predominantly regulated
      by mTOR in muscle cells. Conversely, in liver, the MAPK and phosphatidylinositol
      3-kinase pathways also play an important role, suggesting a tissue-specific
      control. S6K deletion in muscle mimics the effect of the mTOR inhibitor rapamycin
      on rpS6 and eIF4B phosphorylation without affecting eEF2 phosphorylation. To gain
      insight on the functional consequences of these modifications, methionine
      incorporation and polysomal distribution were assessed in muscle cells. Rates and
      rapamycin sensitivity of global translation initiation are not altered in S6K
      deficient muscle cells. In addition, two major pathways of protein degradation,
      autophagy and expression of the muscle-specific atrophy-related E3 ubiquitin
      ligases, are not affected by S6K deletion. Our results do not support a role for
      global translational control in the growth defect due to S6K deletion, suggesting
      specific modes of growth control and translational target regulation downstream
      of mTOR.

PMID- 17494630
TI  - Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt
      metabolism, and cell growth.
AB  - Cardiotonic steroids (CTS), long used to treat heart failure, are endogenously
      produced in mammals. Among them are the hydrophilic cardenolide ouabain and the
      more hydrophobic cardenolide digoxin, as well as the bufadienolides
      marinobufagenin and telecinobufagin. The physiological effects of endogenous
      ouabain on blood pressure and cardiac activity are consistent with the "Na(+)
      lag" hypothesis. This hypothesis assumes that, in cardiac and arterial myocytes,
      a CTS-induced local increase of Na(+) concentration due to inhibition of
      Na(+)/K(+)-ATPase leads to an increase of intracellular Ca(2+) concentration
      ([Ca(2+)](i)) via a backward-running Na(+)/Ca(2+) exchanger. The increase in
      [Ca(2+)](i) then activates muscle contraction. The Na(+)-lag hypothesis may best
      explain short-term and inotropic actions of CTS. Yet all data on the CTS-induced
      alteration of gene expression are consistent with another hypothesis, based on
      the Na(+)/K(+)-ATPase "signalosome," that describes the interaction of cardiac
      glycosides with the Na(+) pump as machinery activating various signaling pathways
      via intramembrane and cytosolic protein-protein interactions. These pathways,
      which may be activated simultaneously or selectively, elevate [Ca(2+)](i),
      activate Src and the ERK1/2 kinase pathways, and activate phosphoinositide 3
      kinase and protein kinase B (Akt), NF-kappaB, and reactive oxygen species. A
      recent development indicates that new pharmaceuticals with antihypertensive and
      anticancer activities may be found among CTS and their derivatives: the
      antihypertensive rostafuroxin suppresses Na(+) resorption and the Src-epidermal
      growth factor receptor-ERK pathway in kidney tubule cells. It may be the parent
      compound of a new principle of antihypertensive therapy. Bufalin and oleandrin or
      the cardenolide analog UNBS-1450 block tumor cell proliferation and induce
      apoptosis at low concentrations in tumors with constitutive activation of NF
      kappaB.

PMID- 17494631
TI  - Angiotensin II inhibits native bTREK-1 K+ channels through a PLC-, kinase C-, and
      PIP2-independent pathway requiring ATP hydrolysis.
AB  - Angiotensin II (ANG II) inhibits bTREK-1 (bovine KCNK2) K(+) channels in bovine
      adrenocortical cells through a Gq-coupled AT(1) receptor by activation of
      separate Ca(2+)- and ATP hydrolysis-dependent signaling pathways. Whole cell
      patch-clamp recording from bovine adrenal zona fasciculata (AZF) cells was used
      to characterize the ATP-dependent signaling mechanism for inhibition of bTREK-1
      by ANG II. We discovered that ATP-dependent inhibition of bTREK-1 by ANG II
      occurred through a novel mechanism that was independent of PLC and its
      established downstream effectors. The ATP-dependent inhibition of bTREK-1 by ANG
      II was not reduced by the PLC antagonists edelfosine and U73122, or by the PKC
      antagonists bisindolylmaleimide I (BIM) or calphostin C. bTREK-1 was partially
      inhibited ( approximately 25%) by the PKC activator phorbol 12,13 dibutyrate
      (PDBu) through an ATP-dependent mechanism that was blocked by BIM. Addition of
      Phosphatidylinositol(4,5) bisphosphate diC8 [DiC(8)PI(4,5)P(2)], a water-soluble
      derivative of phosphotidyl inositol 4,5 bisphosphate (PIP(2)) to the pipette
      solution failed to alter inhibition by ANG II. bTREK-1 inhibition by ANG II was
      also insensitive to antagonists of other protein kinases activated by ANG II in
      adrenocortical cells but was completely blocked by inorganic polytriphosphate
      PPPi. DiC(8)PI(4,5)P(2) was a weak activator of bTREK-1 channels, compared with
      the high-affinity ATP analog N(6)-(2-phenylethyl)adenosine-5'-O-triphosphate (6
      PhEt-ATP). These results demonstrate that the modulation of bTREK-1 channels in
      bovine AZF cells is distinctive with respect to activation by phosphoinositides
      and nucleotides and inhibition by Gq-coupled receptors. Importantly, ANG II
      inhibits bTREK-1 channels through a novel pathway that is different from that
      described for inhibition of native TREK-1 channels in neurons, or cloned channels
      expressed in cell lines. They also indicate that, under physiological conditions,
      ANG II inhibits bTREK-1 and depolarizes AZF cells by two, novel, independent
      pathways that diverge proximal to the activation of PLC.

PMID- 17494632
TI  - Deciphering PiT transport kinetics and substrate specificity using
      electrophysiology and flux measurements.
AB  - Members of the SLC20 family or type III Na(+) -coupled P(i) cotransporters (PiT
      1, PiT-2) are ubiquitously expressed in mammalian tissue and are thought to
      perform a housekeeping function for intracellular P(i) homeostasis. Previous
      studies have shown that PiT-1 and PiT-2 mediate electrogenic P(i) cotransport
      when expressed in Xenopus oocytes, but only limited kinetic characterizations
      were made. To address this shortcoming, we performed a detailed analysis of SLC20
      transport function. Three SLC20 clones (Xenopus PiT-1, human PiT-1, and human PiT
      2) were expressed in Xenopus oocytes. Each clone gave robust Na(+)-dependent
      (32)P(i) uptake, but only Xenopus PiT-1 showed sufficient activity for complete
      kinetic characterization by using two-electrode voltage clamp and radionuclide
      uptake. Transport activity was also documented with Li(+) substituted for Na(+).
      The dependence of the P(i)-induced current on P(i) concentration was Michaelian,
      and the dependence on Na(+) concentration indicated weak cooperativity. The
      dependence on external pH was unique: the apparent P(i) affinity constant showed
      a minimum in the pH range 6.2-6.8 of approximately 0.05 mM and increased to
      approximately 0.2 mM at pH 5.0 and pH 8.0. Xenopus PiT-1 stoichiometry was
      determined by dual (22)Na-(32)P(i) uptake and suggested a 2:1 Na(+):P(i)
      stoichiometry. A correlation of (32)P(i) uptake and net charge movement indicated
      one charge translocation per P(i). Changes in oocyte surface pH were consistent
      with transport of monovalent P(i). On the basis of the kinetics of substrate
      interdependence, we propose an ordered binding scheme of Na(+):H(2)PO(4)(
      ):Na(+). Significantly, in contrast to type II Na(+)-P(i) cotransporters, the
      transport inhibitor phosphonoformic acid did not inhibit PiT-1 or PiT-2 activity.

PMID- 17494633
TI  - Neuropeptide substance P upregulates chemokine and chemokine receptor expression
      in primary mouse neutrophils.
AB  - Neuropeptides play an important role in the active communication between the
      nervous and immune systems. Substance P (SP) is a prominent neuropeptide involved
      in neurogenic inflammation and has been reported to exert various proinflammatory
      actions on inflammatory leukocytes including neutrophils. The present study
      further investigated the modulatory effect of SP (1 muM) on chemokine production
      and chemokine receptor expression in primary mouse neutrophils. Our results
      showed that SP primed neutrophils for chemotactic responses not only to the CXC
      chemokine macrophage inflammatory protein (MIP)-2/CXCL2 but also to the CC
      chemokine MIP-1alpha/CCL3. The activating effect of SP on neutrophils was further
      evidenced by upregulation of the CD11b integrin, the activation marker of
      neutrophils. SP induced both the mRNA and protein expression of the chemokines
      MIP-1alpha/CCL3 and MIP-2/CXCL2 in neutrophils and upregulated the chemokine
      receptors CC chemokine receptor (CCR)-1 and CXC chemokine receptor (CXCR)-2. This
      stimulatory effect on chemokine and chemokine receptor expression in neutrophils
      was further found to be neurokinin-1 receptor (NK-1R) specific. Pretreatment with
      selective NK-1R antagonists inhibited SP-triggered activation of neutrophils and
      chemokine and chemokine receptor upregulation. Moreover, SP-induced chemokine
      upregulation was NF-kappaB dependent. SP time dependently induced NF-kappaB p65
      binding activity, IkappaBalpha degradation, and NF-kappaB p65 nuclear
      translocation in neutrophils. Inhibition of NF-kappaB activation with its
      inhibitor Bay11-7082 (10 muM) abolished SP-induced NF-kappaB binding activity and
      upregulation of MIP-1alpha/CCL3 and MIP-2/CXCL2 in neutrophils. Together, these
      results suggest that SP exerts a direct stimulatory effect on the expression of
      chemokines and chemokine receptors in mouse neutrophils. The effect is NK-1R
      mediated, involving NF-kappaB activation.

PMID- 17494634
TI  - Polyamines upregulate the mRNA expression of cationic amino acid transporter-1 in
      human retinal pigment epithelial cells.
AB  - We previously showed that ornithine was mainly transported via cationic amino
      acid transporter (CAT)-1 in human retinal pigment epithelial (RPE) cell line,
      human telomerase RT (hTERT)-RPE, and that CAT-1 was involved in ornithine
      cytotoxicity in ornithine-delta-aminotransferase (OAT)-deficient cell produced by
      a OAT specific inhibitor, 5-fluoromethylornithine (5-FMO). We showed here that
      CAT-1 mRNA expression was increased by ornithne in OAT-deficient RPE cells, which
      was reversed by an inhibitor of ornithine decarboxylase (ODC), alpha
      difluoromethylornithine (DFMO). Polyamines, especially spermine, one of the
      metabolites of ODC, also enhanced the expression of CAT-1 mRNA. ODC mRNA
      expression was also increased by ornithine and polyamines, and gene silencing of
      ODC by siRNA decreased ornithine transport activity and its cytotoxicity. In
      addition, the mRNA of nuclear protein c-myc was also increased in 5-FMO- and
      ornithine-treated hTERT-RPE cells, and gene silencing of c-myc prevented the
      induction of CAT-1 and ODC. Increases in expression of CAT-1, ODC, and c-myc, and
      the inhibition of these stimulated expression by DFMO were also observed in
      primary porcine RPE cells. These results suggest that spermine plays an important
      role in stimulation of mRNA expression of CAT-1, which is a crucial role in
      ornithine cytotoxicity in OAT-deficient hTERT-RPE cells.

PMID- 17494635
TI  - The roles of myosin ATPase activity and myosin light chain relative content in
      the slowing of type IIB fibers with hindlimb unweighting in rats.
AB  - We tested the hypothesis that slowing of shortening velocity generated by type
      IIB fibers from hindlimb-unweighted (HU) rats resulted from a reduced ATPase
      activity and/or a reduction in the relative content of myosin light chain 3f
      isoform content (MLC(3f)). After 2, 3, and 4 wk of HU, maximal unloaded
      shortening velocity (V(o)) of single permeabilized semimembranosus muscle fibers
      was determined by the slack test. Subsequently, the myosin heavy chain and the
      relative content of MLC were determined by SDS-PAGE. The ratio of MLC(3f) to
      MLC(2f) was determined by densitometric analysis. In addition, myofibrils were
      prepared from permeabilized fibers (soleus and semimembranosus muscles) and
      assayed for resting myosin ATPase and Ca(2+)-activated myosin ATPase. After HU,
      V(o) declined by 28-40% and the MLC(3f)/MLC(2f) ratio decreased by 32 to 48%. A
      significant correlation between the relative amount of MLC(3f) and V(o) was found
      (r = 0.48, P < 0.05). Resting myosin ATPase rates were not different between
      myofibrils prepared from corresponding muscles of control and HU rats (P = 0.86).
      Ca(2+)-activated myosin ATPase activities also were not different between
      myofibrils prepared from corresponding muscles of control and HU rats (P = 0.13).
      These data suggest that the slowing of maximal unloaded shortening velocity in
      type IIB fibers with HU is, at least in part, due to a relative change in the
      essential light chain composition, a decrease in the relative amount of MLC(3f)
      and most likely a concomitant increase in MLC(1f). However, this reduction in
      V(o) is independent of myosin ATPase activity.

PMID- 17494636
TI  - Seroprevalence of bactericidal and anti-outer membrane vesicle antibodies to
      Neisseria meningitidis group B in England.
AB  - Outer membrane vesicle (OMV) and recombinant protein-based vaccines targeted
      against multiple strains of group B meningococci are under development. The serum
      bactericidal antibody (SBA) assay has been designated the surrogate of
      protection, but the exact cutoff has not been determined. We measured the SBA
      titers in 2,415 serum samples and the anti-OMV IgG antibody concentrations in
      2,672 serum samples representative of the English population to establish a
      baseline of natural immunity. SBA and anti-OMV IgG antibody titers are high in
      infants in the first 3 months of life, declining thereafter, presumably as
      maternal immunity wanes. About 6% of the subjects in the 1- to 11-year-old age
      group had SBA titers >or=4. During the teenage years, there was a marked increase
      in the percentage of subjects with SBA titers >or=4, rising to over 50% in 19
      year-olds, with about 20% of older adults achieving this titer. The peak in SBA
      and anti-OMV IgG titers coincided with the peak in meningococcal carriage. Simple
      mathematical models confirm that the relationship between observed seroprevalence
      and carriage by age is consistent with carriage inducing SBA and that following
      an episode of carriage, SBA levels may remain elevated for many months. With the
      exception of children aged 3 to 11 months, there was no clear relationship
      between disease incidence and seroprevalence.

PMID- 17494637
TI  - Needle-free skin patch delivery of a vaccine for a potentially pandemic influenza
      virus provides protection against lethal challenge in mice.
AB  - In the event of another influenza virus pandemic, strategies for effective mass
      vaccination will urgently be needed. We used a novel transdermal patch delivery
      technology, known as the PassPort system, to vaccinate mice with recombinant H5
      hemagglutinin with or without immunomodulators. This needle-free form of vaccine
      delivery induced robust serum antibody responses that were augmented by different
      immunomodulators that stimulated the innate immune system and protected mice
      against lethal challenge with a highly pathogenic avian H5N1 influenza virus.

PMID- 17494639
TI  - Contamination by cardboard particles as a cause of false-positive results for
      Aspergillus galactomannan enzyme immunoassays.

PMID- 17494638
TI  - Functional and specific antibody responses in adult volunteers in new zealand who
      were given one of two different meningococcal serogroup B outer membrane vesicle
      vaccines.
AB  - This study presents detailed analyses of total and specific serum antibody levels
      among 26 and 24 adult volunteers before vaccination and after the third dose of
      the meningococcal serogroup B outer membrane vesicle (OMV) vaccines MeNZB and
      MenBvac, respectively, in a clinical trial in New Zealand (V. Thornton, D.
      Lennon, K. Rasanathan, J. O'Hallahan, P. Oster, J. Stewart, S. Tilman, I.
      Aaberge, B. Feiring, H. Nokleby, E. Rosenqvist, K. White, S. Reid, K. Mulholland,
      M. J. Wakefield, and D. Martin, Vaccine 24:1395-1400, 2006). With the homologous
      vaccine strains as targets, both vaccines induced significant increases in serum
      bactericidal and opsonophagocytic activities and in the levels of immunoglobulin
      G (IgG) to OMV antigens in an enzyme-linked immunosorbent assay (ELISA) and to
      live meningococci by flow cytometry. They also induced high levels of activity
      against the heterologous strains, particularly in terms of opsonophagocytic
      activity and IgG binding to live bacteria. The antibody levels with the
      homologous and heterologous strains in the four assays showed high and
      significant positive correlations. Specific IgG binding to 10 major OMV antigens
      in each vaccine was measured by scanning of immunoblots; ELISAs for two antigens,
      lipopolysaccharide and Neisseria surface protein A (NspA), were also performed.
      Both vaccines elicited significant increases in IgG binding to all homologous and
      heterologous OMV antigens except NspA. The total IgG band intensity on the blots
      correlated significantly with the IgG levels determined by the OMV ELISA and flow
      cytometry. In conclusion, the results of the various immunological assays showed
      that both OMV vaccines gave rise to high levels of specific and cross-reacting
      antibodies.

PMID- 17494640
TI  - Induction of specific immune responses by severe acute respiratory syndrome
      coronavirus spike DNA vaccine with or without interleukin-2 immunization using
      different vaccination routes in mice.
AB  - DNA vaccines induce humoral and cellular immune responses in animal models and
      humans. To analyze the immunogenicity of the severe acute respiratory syndrome
      (SARS) coronavirus (CoV), SARS-CoV, spike DNA vaccine and the immunoregulatory
      activity of interleukin-2 (IL-2), DNA vaccine plasmids pcDNA-S and pcDNA-IL-2
      were constructed and inoculated into BALB/c mice with or without pcDNA-IL-2 by
      using three different immunization routes (the intramuscular route,
      electroporation, or the oral route with live attenuated Salmonella enterica
      serovar Typhimurium). The cellular and humoral immune responses were assessed by
      enzyme-linked immunosorbent assays, lymphocyte proliferation assays, enzyme
      linked immunospot assays, and fluorescence-activated cell sorter analyses. The
      results showed that specific humoral and cellular immunities could be induced in
      mice by inoculating them with SARS-CoV spike DNA vaccine alone or by
      coinoculation with IL-2-expressing plasmids. In addition, the immune response
      levels in the coinoculation groups were significantly higher than those in groups
      receiving the spike DNA vaccine alone. The comparison between the three
      vaccination routes indicated that oral vaccination evoked a vigorous T-cell
      response and a weak response predominantly with subclass immunoglobulin G2a
      (IgG2a) antibody. However, intramuscular immunization evoked a vigorous antibody
      response and a weak T-cell response, and vaccination by electroporation evoked a
      vigorous response with a predominant subclass IgG1 antibody response and a
      moderate T-cell response. Our findings show that the spike DNA vaccine has good
      immunogenicity and can induce specific humoral and cellular immunities in BALB/c
      mice, while IL-2 plays an immunoadjuvant role and enhances the humoral and
      cellular immune responses. Different vaccination routes also evoke distinct
      immune responses. This study provides basic information for the design of DNA
      vaccines against SARS-CoV.

PMID- 17494641
TI  - Lipopolysaccharide analogs improve efficacy of acellular pertussis vaccine and
      reduce type I hypersensitivity in mice.
AB  - Pertussis is an infectious disease of the respiratory tract that is caused by the
      gram-negative bacterium Bordetella pertussis. Although acellular pertussis (aP)
      vaccines are safe, they are not fully effective and thus require improvement. In
      contrast to whole-cell pertussis (wP) vaccines, aP vaccines do not contain
      lipopolysaccharide (LPS). Monophosphoryl lipid A (MPL) and Neisseria meningitidis
      LpxL2 LPS have been shown to display immune-stimulating activity while exerting
      little endotoxin activity. Therefore, we evaluated whether these LPS analogs
      could increase the efficacy of the aP vaccine. Mice were vaccinated with
      diphtheria-tetanus-aP vaccine with aluminum, MPL, or LpxL2 LPS adjuvant before
      intranasal challenge with B. pertussis. Compared to vaccination with the aluminum
      adjuvant, vaccination with either LPS analog resulted in lower colonization and a
      higher pertussis toxin-specific serum immunoglobulin G level, indicating
      increased efficacy. Vaccination with either LPS analog resulted in reduced lung
      eosinophilia, reduced eosinophil numbers in the bronchoalveolar lavage fluid, and
      the ex vivo production of interleukin-4 (IL-4) by bronchial lymph node cells and
      IL-5 by spleen cells, suggesting reduced type I hypersensitivity. Vaccination
      with either LPS analog increased serum IL-6 levels, although these levels
      remained well below the level induced by wP, suggesting that supplementation with
      LPS analogs may induce some reactogenicity but reactogenicity considerably less
      than that induced by the wP vaccine. In conclusion, these results indicate that
      supplementation with LPS analogs forms a promising strategy that can be used to
      improve aP vaccines.

PMID- 17494642
TI  - 6-Hydroxybuspirone is a major active metabolite of buspirone: assessment of
      pharmacokinetics and 5-hydroxytryptamine1A receptor occupancy in rats.
AB  - The pharmacokinetics and in vivo potency of 6-hydroxybuspirone (6-OH-buspirone),
      a major metabolite of buspirone, were investigated. The plasma clearance (47.3 +/
      3.5 ml/min/kg), volume of distribution (2.6 +/- 0.3 l/kg), and half-life (1.2 +/
      0.2 h) of 6-OH-buspirone in rats were similar to those for buspirone.
      Bioavailability was higher for 6-OH-buspirone (19%) compared with that for
      buspirone (1.4%). After intravenous infusions to steady-state levels in plasma, 6
      OH-buspirone and buspirone increased 5-hydroxytryptamine (HT)(1A) receptor
      occupancy in a concentration-dependent manner with EC(50) values of 1.0 +/- 0.3
      and 0.38 +/- 0.06 microM in the dorsal raphe and 4.0 +/- 0.6 and 1.5 +/- 0.3
      microM in the hippocampus, respectively. Both compounds appeared to be
      approximately 4-fold more potent in occupying presynaptic 5-HT(1A) receptors in
      the dorsal raphe than the postsynaptic receptors in the hippocampus. Oral dosing
      of buspirone in rats resulted in exposures (area under the concentration-time
      profile) of 6-OH-buspirone and 1-(2-pyrimidinyl)-piperazine (1-PP), another major
      metabolite of buspirone, that were approximately 12 (6-OH-buspirone)- and 49 (1
      PP)-fold higher than the exposure of the parent compound. As a whole, these
      preclinical data suggest that 6-OH-buspirone probably contributes to the clinical
      efficacy of buspirone as an anxiolytic agent.

PMID- 17494644
TI  - Frequency of the frame-shifting CYP2D7 138delT polymorphism in a large,
      ethnically diverse sample population.
AB  - Cytochrome P450 2D7 (CYP2D7) has long been considered a pseudogene. A recent
      report described an indel polymorphism (CYP2D7 138delT) that causes a frameshift
      generating an open reading frame and functional protein. This polymorphism was
      observed in 6 of 12 samples from an Indian population. Individuals with the
      138delT polymorphism expressed CYP2D7 protein from a brain-specific,
      alternatively spliced transcript (J Biol Chem 279:27383-27389, 2004). The
      unexpectedly high frequency of the variant allele and resulting CYP2D7 expression
      could have important implications for brain-specific metabolism of CYP2D
      substrates including many psychoactive drugs. However, the 138delT variant has
      not been detected in other studies (Pharmacogenetics 11:45-55, 2001; Biochem
      Biophys Res Commun 336:1241-1250, 2005). Our goal was to determine the frequency
      of this variant in a larger, ethnically diverse population. CYP2D7 138delT
      genotypes for 163 Caucasians, 95 East Asians, 50 Indians, 68 Hispanic Latinos,
      and 68 African Americans were determined by Pyrosequencing. The 138delT allele
      was observed at a frequency of 1.0% in East Asians and 0.74% in Hispanic Latinos.
      The deletion was not observed in Indians or the other ethnic populations. In
      addition, in each of the three samples with 138delT, the putative brain-specific
      transcript contains a premature stop codon that would preclude protein
      expression. The low frequency of the CYP2D7 138delT polymorphism in our
      ethnically diverse sample, and particularly the absence from 50 Indian samples,
      is in contrast to the high frequency previously reported. Our results suggest
      that CYP2D7 138delT is unlikely to be highly relevant for population variation of
      pharmacokinetics or drug response.

PMID- 17494643
TI  - Mutational analysis of a highly conserved proline residue in MRP1, MRP2, and MRP3
      reveals a partially conserved function.
AB  - The ATP-binding cassette multidrug resistance protein 1 MRP1 (ABCC1) mediates the
      cellular efflux of organic anions including conjugated metabolites,
      chemotherapeutic agents, and toxicants. We previously described a mutation in
      cytoplasmic loop 7 (CL7) of MRP1, Pro1150Ala, which reduced leukotriene C(4)
      (LTC(4)) transport but increased 17beta-estradiol 17beta-d-glucuronide
      (E(2)17betaG) and methotrexate (MTX) transport. Vanadate-induced trapping of
      [alpha-(32)P]8N(3)ADP by the Pro1150Ala mutant in the absence of substrate was
      also greatly reduced compared with wild-type MRP1 suggesting an uncoupling of ATP
      hydrolysis and transport activity. To determine whether the functional importance
      of MRP1-Pro(1150) is conserved, the analogous Pro(1158) and Pro(1147) residues in
      the MRP2 and MRP3 transporters, respectively, were mutated to Ala. Expression
      levels of the three mutants were unaffected; however, the vesicular transport
      activity of at least one organic anion substrate was significantly altered. As
      observed for MRP1-Pro1150Ala, LTC(4) transport by MRP2-Pro1158Ala was decreased.
      However, E(2)17betaG and MTX transport was comparable with that of wild-type MRP2
      rather than increased as was observed for MRP1-Pro1150Ala. In the case of MRP3
      Pro1147Ala, LTC(4) transport was increased, whereas E(2)17betaG transport was
      unaffected. MTX transport by MRP3-Pro1147Ala was also increased but to a lesser
      extent than for MRP1-Pro1150Ala. In contrast, all three mutants showed a marked
      reduction in levels of vanadate-induced trapped [alpha-(32)P]8N(3)ADP. We
      conclude that MRP1-Pro(1150), MRP2-Pro(1158), and MRP3-Pro(1147) in CL7 differ in
      their influence on substrate specificity but share a common role in the
      nucleotide interactions of these transporters.

PMID- 17494647
TI  - Ready or not, here they come: randomized trials evaluating new endovascular
      aneurysm therapies.
AB  - Randomized trials evaluating endovascular therapy are currently underway. The
      results of these trials will present us with both new answers and new questions.

PMID- 17494648
TI  - Basilar artery stent angioplasty for symptomatic intracranial athero-occlusive
      disease: complications and late midterm clinical outcomes.
AB  - BACKGROUND AND PURPOSE: After an initial series of basilar artery stent
      angioplasty indicated a high technical success rate and minimal morbidity,
      subsequent reports suggested significant procedural risks. We retrospectively
      reviewed our experience with basilar artery stent placement to assess
      complications and clinical outcomes. MATERIALS AND METHODS: Ten consecutive
      patients with symptomatic intracranial athero-occlusive disease underwent stent
      placement of the basilar artery at our institution (1999-2003). We collected
      clinical data by chart review and determined outcomes (modified Rankin Scale
      [mRS]) by telephone interview. Angiographic data were analyzed by 2 blinded
      investigators. Clinical and angiographic variables were tested for correlation
      with outcome and complications using the Pearson correlation test. RESULTS: Of 10
      patients (mean follow-up time, 31 months), 4 patients suffered 6 ischemic
      complications that were immediate in 1, early delayed (<2 weeks) in 4, and late
      delayed (>2 weeks) in 1. Complications included basilar artery rupture in 1
      patient, access site complications in 1 patient, and other non-neurologic
      complications in 5. Symptomatic restenosis occurred in 1 patient. Outcomes (mRS)
      were excellent (0-2) in 5 patients, good (3) in 4, and poor (4-6) in 1 patient,
      who died. Ischemic complications were associated with lesion lumen <or=0.5 mm and
      lesion angulation >45 degrees (P<.05). Less favorable clinical outcomes were
      associated with few ischemic complications and the presence of fewer than 2
      patent vertebral arteries (P<.05). CONCLUSIONS: Despite a significant incidence
      of ischemic and nonischemic complications after basilar artery stent placement,
      most patients in this small series achieved freedom from vertebrobasilar ischemia
      and good to excellent clinical outcomes at late midterm follow-up (12-46 months).
      Ischemic complications usually had an early delayed presentation and procedural
      risks correlated with lesion characteristics.

PMID- 17494649
TI  - Self-expanding stents for recanalization of acute cerebrovascular occlusions.
AB  - BACKGROUND AND PURPOSE: Stent-assisted revascularization increases prevailing
      recanalization rates ( congruent with 50%-69%) for vessel occlusions recalcitrant
      to thrombolytics. Although balloon-mounted coronary stents can displace thrombus
      (via angioplasty) and retain clot along vessel walls, intracranial self-expanding
      stents are more flexible and exert less radial outward force during deployment,
      increasing deliverability and safety. To understand the effectiveness of self
      expanding stents for recanalization of acute cerebrovascular occlusions, we
      retrospectively reviewed our preliminary experience with these stents. MATERIALS
      AND METHODS: Eighteen patients (19 lesions) presenting with a clinical diagnosis
      of acute stroke underwent catheter-based angiography documenting focal occlusion
      of an intracranial artery. A self-expanding stent was delivered to the occlusion
      and deployed. Stent placement was the initial mechanical maneuver in 6 cases;
      others involved a combination of pharmacologic and/or mechanical maneuvers
      prestenting. GP IIb/IIIa inhibitors were administered in 10 cases
      intraprocedurally or immediately postprocedurally to avoid acute in-stent
      thrombosis. RESULTS: Stent deployment at the target occlusion (technical success)
      was achieved in all cases. Thrombolysis in Cerebral Ischemia (TICI)/Thrombolysis
      in Myocardial Ischemia (TIMI) 2/3 recanalization (angiographic success) was
      achieved in 15 of 19 lesions (79%). All single-vessel lesions (n=8) were
      recanalized, but only 7 of 11 combination internal carotid artery and middle
      cerebral artery lesions were recanalized. No intraprocedural complications
      occurred. Seven in-hospital deaths occurred: stroke progression, 4; intracranial
      hemorrhage, 2; respiratory failure, 1. Seven patients had >or=4-point National
      Institutes of Health Stroke Scale improvement within 24 hours after the
      procedure, 6 had modified Rankin Score (mRS) <or=3 at discharge, and 4 had mRS
      <or=3 at 3 months. Overall, revascularization and improvement in clinical outcome
      were more likely to occur in women. CONCLUSION: Feasibility of self-expanding
      stents for treatment of acute symptomatic intracranial occlusions is shown. For
      single-vessel lesions, stent placement with concomitant administration of
      IIb/IIIa inhibitors contributed to the achievement of recanalization rates
      exceeding those currently reported for other means of thrombolysis.

PMID- 17494650
TI  - Stent conformity in curved vascular models with simulated aneurysm necks using
      flat-panel CT: an in vitro study.
AB  - BACKGROUND AND PURPOSE: Radiographic visibility of self-expandable intracranial
      stents is insufficient for assessment of conformability and deployment
      characteristics. The purpose of this study was to evaluate stent mechanics in a
      curved vessel model by using Flat-Panel CT (FPCT). MATERIALS AND METHODS: The
      following stents were used: Neuroform 2, Neuroform Treo, Enterprise, and LEO. All
      stents were bent in the same polytetrafluoroethylene tubes with various angles
      ranging from 150 degrees to 30 degrees . To visualize potential prolapse of the
      stent struts, 4-, 5-, and 8-mm openings were created. FPCTs were obtained using a
      C-arm with flat detector. RESULTS: FPCT scans provided excellent visualization of
      deployment characteristics and stent mechanics and was superior to digital
      subtraction angiography (DSA) and digital radiography (DR). The Neuroform2/Treo
      showed, with increasing angle and diameter of the opening, a continuous increase
      in cell size. These stents also showed an outward prolapse at the convexity and
      an inwards prolapse of struts at the concavity of the curvature. The Enterprise
      showed an increasing trend to flatten and to kink with curvatures that are more
      acute. The LEO showed fewer trends to kink but an inward crimping of its ends
      with more acute angles. CONCLUSIONS: Deployment characteristics and
      conformability to a curved vessel model vary considerably, depending on the angle
      and the stent design. Adverse mechanics such as increased cell opening, strut
      prolapse, flattening, and kinking occur during stent placement in a curved vessel
      model, and may gain clinical importance. FPCT is superior to DSA and DR in
      visualizing small metallic stents and enables accurate detection of adverse stent
      mechanics.

PMID- 17494651
TI  - Apollo stent for symptomatic atherosclerotic intracranial stenosis: study
      results.
AB  - BACKGROUND AND PURPOSE: A recent trial shows an 8.3 per 100-patient-years'
      ischemic stroke rate in the territory of the intracranial stenotic artery,
      despite aspirin treatment. Our aim was to prospectively study the feasibility and
      outcome of a new intracranial balloon-expandable Apollo stent for symptomatic
      atherosclerotic intracranial stenosis (SAIS). MATERIALS AND METHODS: Forty-six
      patients (41 men and 5 women; median, 54 years of age) with forty-eight >or=50%
      SAISs were enrolled. Procedural feasibility was evaluated by stent success
      (residual stenosis <or=30%) and procedural time. The primary end point was
      ischemic stroke in the target-lesion artery territory, including any stroke and
      death within 30 days. RESULTS: Forty-four lesions (91.7%) obtained stent success
      within a median procedural time of 50.6 minutes. Severe tortuosity correlated
      with stent failure. Three patients (6.5%, 3/46) had minor strokes within 30 days.
      All patients were available for follow-up (46 had 30-day follow-up, 45 had 6
      month follow-up, 44 had 12- and 18-month follow-up, and 24 had follow-up of
      >or=24 months), which varied from 1 month to 30.7 months (median, 23.9 months).
      After 30 days, 1 patient (2.2%, 1/46) developed minor stroke in the target-lesion
      artery territory at 6.7 months. Primary end point rate was 4.3 per 100 patient
      years. Angiographic follow-up was performed in 25 patients. Seven restenoses
      (28%, 7/25) were detected, 1 of which was symptomatic. CONCLUSION: Angioplasty
      with the Apollo stent for symptomatic atherosclerotic intracranial stenosis is
      feasible. Severe tortuosity is an independent predictor of stent failure. Our
      clinical outcome seems to compare favorably with results of aspirin therapy, but
      the restenotic rate was high.

PMID- 17494652
TI  - Time-resolved MR angiography: optimal parallel imaging method.
AB  - BACKGROUND AND PURPOSE: Time-resolved (TR) MR angiography (MRA) using parallel
      imaging techniques is proving to have clinical utility for improving MRA spatial
      and temporal resolution and separating arterial from venous anatomy. The purpose
      of this study was to evaluate TR MRA of the intracranial vessels at different
      integrated parallel acquisition technique (IPAT) factors. MATERIALS AND METHODS:
      3D TR MRA using time-resolved echo-shared angiographic technique was performed
      with different IPAT factors (0, 2, 3) at 1.5 T, resulting in temporal resolutions
      of 4.0, 1.7, and 1.3 seconds, respectively. We studied 14 subjects, comprising 12
      patients with various pathologic conditions and 2 healthy subjects. The brain
      volume was covered by 36 partitions, and a bolus of 5 mL of gadopentate
      dimeglumine was administered. Signal-to-noise ratio (SNR), contrast-to-noise
      ratio (CNR), the number of frames that distinguished between arterial and venous
      phases, the conspicuity of the vasculature, and artifacts were analyzed. RESULTS:
      There was no significant difference in SNR between IPAT factors 0 and 2.
      Moreover, SNR was significantly lower with IPAT 3 than with IPAT 0 or 2. Smaller
      vessel segments (M3 and P3) were rated significantly inferior with TR MRA IPAT 2
      or 3 compared with MRA without IPAT. For larger proximal vessels (A1 and A2
      segments of anterior cerebral artery, M1 and M2 segments of middle cerebral
      artery, P2 segment of posterior cerebral artery, and basilar artery), there was
      no difference between TR MRA IPAT 0 and 2. CONCLUSION: To obtain arterial and
      venous information in a clinical setting, intracranial TR MRA is best performed
      with an IPAT factor of 2 with at least 5 mL of contrast.

PMID- 17494653
TI  - 3D digital subtraction angiography of intracranial aneurysms: comparison of flat
      panel detector with conventional image intensifier TV system using a vascular
      phantom.
AB  - BACKGROUND AND PURPOSE: Compared with the image intensifier (I.I.)-TV system, the
      flat panel detector (FPD) system of direct conversion type has several theoretic
      advantages, such as higher spatial resolution, wide dynamic range, and no image
      distortion. The purpose of this study was to compare the image quality of 3D
      digital subtraction angiography (DSA) in the FPD and conventional I.I.-TV systems
      using a vascular phantom. MATERIALS AND METHODS: An anthropomorphic vascular
      phantom was designed to simulate the various intracranial aneurysms with
      aneurysmal bleb. The tubes of this vascular phantom were filled with 2
      concentrations of contrast material (300 and 150 mg I/mL), and we obtained 3D DSA
      using the FPD and I.I.-TV systems. First, 2 blinded radiologists compared the
      volume-rendering images for 3D DSA on the FPD and I.I.-TV systems, looking for
      pseudostenosis artifacts. Then, 2 other radiologists independently evaluated both
      systems for the depiction of the simulated aneurysm and aneurysmal bleb using a 5
      point scale. RESULTS: For the degree of the pseudostenosis artifacts at the M1
      segment of the middle cerebral artery at 300 mg I/mL, 3D DSA with FPD system
      showed mild stenoses, whereas severe stenoses were observed at 3D DSA with I.I.
      TV system. At both concentrations, the FPD system was significantly superior to
      I.I.-TV system regarding the depiction of aneurysm and aneurysmal bleb.
      CONCLUSION: Compared with the I.I.-TV system, the FPD system could create high
      resolution 3D DSA combined with a reduction of the pseudostenosis artifacts.

PMID- 17494654
TI  - Safety and feasibility of intra-arterial nicardipine for the treatment of
      subarachnoid hemorrhage-associated vasospasm: initial clinical experience with
      high-dose infusions.
AB  - BACKGROUND AND PURPOSE: Delayed cerebral ischemia from vasospasm is a major
      complication after aneurysmal subarachnoid hemorrhage (SAH), but complications
      and/or low efficacy are associated with current therapy. We report our initial
      experience with intra-arterial use of a calcium channel blocker, nicardipine.
      MATERIALS AND METHODS: A retrospective review of a consecutive series of patients
      with clinical and angiographic vasospasm treated with intra-arterial nicardipine
      was performed. Standard criteria for definition of significant, intractable
      vasospasm after aneurysmal SAH were used. After catheter angiographic
      confirmation of vasospasm, arteries showing severe narrowing were targeted for
      superselective catheterization. Nicardipine was infused at a high dose rate
      (0.415-0.81 mg/min). Contrast injections were performed at 2-5-mg intervals to
      assess effective response (a 60% increase in arterial diameter of the most
      severely decreased in caliber vessel compared with the very first angiographic
      run). RESULTS: Eleven consecutive patients underwent a total of 20 procedures;
      most had SAH with high Hunt and Hess grades (III or IV). All had depressed level
      of consciousness; others had paresis (7/20, 35%), aphasia (1/20, 5%), and facial
      nerve palsy (1/20, 5%). Between 10 and 40 mg of nicardipine was used. A 60%
      increase in diameter of the main affected artery compared with the initial
      diameter measured in the initial angiographic run was achieved in all procedures.
      Clinical improvement (resolved focal symptoms or increased Glasgow Coma Score)
      occurred in 10 of 11 patients (91%). One patient died from complications of the
      initial hemorrhage. No complications occurred after 16 of 20 procedures (80%);
      minor complications without sequelae occurred after the remaining procedures.
      Follow-up of at least 2 months in 10 survivors revealed minor or no deficits in
      most patients with a Glasgow Outcome Score of 1 or 2 in 9 of 10 patients (90%).
      CONCLUSION: In this small series, high-dose intra-arterial nicardipine infusion
      to treat SAH-associated vasospasm seems to be safe and effective.

PMID- 17494655
TI  - Endovascular treatment of aneurysms: healing mechanisms in a Swine model are
      associated with increased expression of matrix metalloproteinases, vascular cell
      adhesion molecule-1, and vascular endothelial growth factor, and decreased
      expression of tissue inhibitors of matrix metalloproteinases.
AB  - BACKGROUND AND PURPOSE: The mechanism of aneurysm healing after coiling remains
      poorly understood. The purpose of the study was to obtain a better understanding
      of the cellular and molecular events that are associated with aneurysm healing
      after endovascular coiling in a swine aneurysm model. MATERIALS AND METHODS:
      Twenty sidewall aneurysms were created surgically in common carotid arteries in
      10 swine. These aneurysms were embolized immediately after creation by using
      platinum coils by endovascular means. Two and 12 weeks after implantation,
      aneurysm samples were collected for histologic and biochemical analysis. RESULTS:
      All aneurysms were completely or nearly completely occluded angiographically at
      the time of embolization and at follow-up. At 2 weeks, aneurysm cavities were
      filled with inflammatory cells and myofibroblasts. At 12 weeks, aneurysm cavities
      were filled with richly vascularized fibrous tissue and disorganized collagen
      bundles. The expression of matrix metalloproteinase (MMP)-2 and -9 was found to
      be elevated at 2 weeks. Expression remained greater than that in control tissue
      at 12 weeks but was significantly decreased compared with the earlier time point.
      Expression of tissue inhibitors of MMPs (TIMPs) was diminished at both time
      points. Expression of vascular cell adhesion molecule-1 (VCAM-1) and vascular
      endothelial growth factor (VEGF) was elevated at both 2 weeks and 12 weeks.
      Endothelial nitric oxide synthase expression was not different from that in
      controls. Transforming growth factor-beta expression was elevated at 2 weeks
      only. CONCLUSION: The coil occlusion in this model that is prone to heal is
      associated with increased expression of MMP-2, MMP-9, VCAM-1, and VEGF, and
      decreased expression of TIMPs.

PMID- 17494656
TI  - Control of aneurysm volume by adjusting the position of ligation during creation
      of elastase-induced aneurysms: a prospective study.
AB  - BACKGROUND AND PURPOSE: Animal models with appropriate volume are crucial for
      preclinical assessment of aneurysm therapies. Our purpose was to control the
      aneurysm volume by adjusting the position of ligation during creation of elastase
      induced aneurysms in rabbits. MATERIALS AND METHODS: Sixty elastase-induced
      aneurysms in rabbits were created. Two different methods were used for creation,
      including group 1 (n=30) by using a lower ligation (from the origin of the right
      common carotid artery [RCCA] to the ligation point, 10 mm) and group 2 (n=30) by
      using a higher ligation (from the origin of the RCCA to the ligation point, 15
      mm). Aneurysm sizes (neck diameter, width, and height) and volumes in the 2
      groups were measured and calculated, and they were compared by using the Student
      t test. RESULTS: The mean aneurysm neck diameter, width, and height for group 2
      were significantly larger than those of group 1 (3.3 +/- 0.8 versus 2.7 +/- 0.6
      mm, P<.001; 3.7 +/- 0.7 versus 2.5 +/- 0.7 mm, P<.001; 9.0 +/- 1.7 versus 7.3 +/-
      1.9 mm, P<.001, respectively). The aneurysm volume in group 2 was significantly
      larger than that in group 1 (102.4 +/- 54.8 mm(3) versus 36.6 +/- 26.8 mm(3),
      P<.001). CONCLUSION: The aneurysm volume of elastase-induced models in rabbits
      can be controlled by adjusting the position of the ligation. Using a higher
      ligation can create relatively more voluminous aneurysms, compared with using a
      lower ligation.

PMID- 17494657
TI  - Rapid intracranial clot removal with a new device: the alligator retriever.
AB  - BACKGROUND AND PURPOSE: Despite availability of an approved drug to treat acute
      cerebral ischemia, most patients with stroke do not realize a good outcome. A
      method that would rapidly increase or restore cerebral perfusion before
      irreversible cell death should improve patient outcomes. MATERIALS AND METHODS:
      We recently had the opportunity to treat 6 middle-aged-to-elderly patients who
      presented with signs and symptoms of acute cerebral ischemia, by mechanically
      removing their (predominantly) middle cerebral artery clots by using a new
      retrieval device that had been previously approved by the US Food and Drug
      Administration for intravascular retrieval of foreign bodies. During a 2-month
      period, the 6 patients were treated in 5 separate institutions. No patient had an
      unsuccessful attempt at clot removal. The cases were collected by personal
      communication with each operator. RESULTS: In all instances, use of the device
      resulted in rapid clot removal. Each patient had a large improvement in National
      Institutes of Health Stroke Scale score. Two of the 6 patients had experienced
      failure of another clot retrieval device, and 3 patients required no systemic
      thrombolytics, reducing the likelihood of one of the most feared complications of
      stroke therapy, intracranial hemorrhage. SUMMARY: We believe that use of this
      device may result in improved outcomes for patients with acute ischemic stroke.
      In our limited experience, it provided a rapid, safe, and effective means for
      achieving revascularization.

PMID- 17494658
TI  - mRNA expression in rabbit experimental aneurysms: a study using gene chip
      microarrays.
AB  - BACKGROUND AND PURPOSE: The molecular characteristics of intracranial aneurysms
      are still poorly documented. A rabbit elastase aneurysm model has been helpful in
      the evaluation of devices and strategies involved in endovascular treatment of
      aneurysms. The goal of this project was to document the molecular changes,
      assessed by gene chip microarrays, associated with the creation of aneurysms in
      this model compared with the contralateral carotid artery. MATERIALS AND METHODS:
      A microarray of rabbit genes of interest was constructed using rabbit nucleotide
      sequences from GenBank. Elastase-induced saccular aneurysms were created at the
      origin of the right common carotid artery in 4 rabbits. Twelve weeks after
      aneurysm creation, RNA was isolated from the aneurysm as well as the
      contralateral common carotid artery and used for microarray experiments. Reverse
      transcription-polymerase chain reaction (RT-PCR) was performed on 1 animal as a
      confirmatory test. RESULTS: Ninety-six (46%) of 209 genes in the microarray were
      differentially expressed in the rabbit aneurysm compared with the contralateral
      common carotid artery. In general, differential gene expression followed specific
      molecular pathways. Similarities were found between rabbit aneurysms and human
      intracranial aneurysms, including increased metalloproteinase activity and
      decreased production of the extracellular matrix. RT-PCR results confirmed the
      differential expression found by the gene chip microarray. CONCLUSIONS: The
      molecular characteristics of the rabbit elastase-induced saccular aneurysm are
      described. The rabbit aneurysm model shares some molecular features with human
      intracranial aneurysms. Future studies can use the rabbit model and the new
      rabbit gene chip microarray to study the molecular aspects of saccular aneurysms.

PMID- 17494659
TI  - Artery of Percheron thrombolysis.
AB  - SUMMARY: A patient with acute top of the basilar syndrome clinically was found to
      have only a small basilar artery filling defect but complete occlusion of the
      artery of Percheron. Intra-arterial thrombolysis resulted in favorable neurologic
      outcome. To our knowledge, this is the only case of angiographically proved and
      treated artery of Percheron occlusion. The value of this report is that
      reperfusion of ischemic areas was only achieved when persistent investigation
      disclosed artery of Percheron occlusion.

PMID- 17494660
TI  - Embolectomy in a rabbit acute arterial occlusion model using a novel
      electromechanical extraction device.
AB  - A prototype endovascular electromechanical clot-extraction device was fabricated
      using a combination of shape memory polymer and shape memory nickel-titanium
      alloy (nitinol). Five embolic vascular occlusions were created in 4 rabbits by
      injecting thermally coagulated blood through a 4F catheter in the common carotid
      artery. Angiography immediately after clot injection showed complete or partial
      occlusion of the common carotid artery. Posttreatment angiography showed complete
      (2/5), partial (2/5), or no (1/5) restoration of blood flow.

PMID- 17494661
TI  - Segmental artery exchange technique for stable 4F guiding-catheter positioning in
      embolization of spinal vascular malformations.
AB  - For anatomic and technical reasons, it is often difficult to achieve guiding
      catheter stability in the segmental arteries during embolization of spinal
      vascular lesions. We have developed a segmental artery exchange technique using a
      thin-walled 4F nontapered catheter that is safe and achieves a stable guiding
      catheter position. This catheter accommodates both the flow-guided and variable
      stiffness microcatheters, allowing selective catheterization and treatment of
      spinal vascular lesions.

PMID- 17494662
TI  - MR angiography of dural arteriovenous fistulas: diagnosis and follow-up after
      treatment using a time-resolved 3D contrast-enhanced technique.
AB  - BACKGROUND AND PURPOSE: Digital subtraction angiography (DSA) is the method of
      reference for imaging of dural arteriovenous fistula (DAVF). The goal of this
      study was to analyze the value of different MR images including 3D contrast
      enhanced MR angiography (MRA) with a high temporal resolution in diagnostic and
      follow-up imaging of DAVFs. MATERIALS AND METHODS: A total of 18 MR/MRA
      examinations from 14 patients with untreated (n=9) and/or treated (n=9) DAVFs
      were evaluated. Two observers assessed all MR and MRA investigations for signs
      indicating the presence of a DAVF, for fistula characteristics such as fistula
      grading, location of fistulous point, and fistula obliteration after treatment.
      All results were compared with DSA findings. RESULTS: On time-resolved 3D
      contrast-enhanced (TR 3D) MRA, the side and presence of all patent fistulas
      (n=13) were correctly indicated, and no false-positive findings were observed in
      occluded DAVFs (n=5). Grading of fistulas with this imaging technique was correct
      in 77% and 85% of patent fistulas for both readers, respectively. On T2-weighted
      images, signs indicative of a DAVF were encountered only in fistulas with
      cortical venous reflux (56%), whereas on 3D time-of-flight (TOF) MRA, most
      fistulas (88%) were correctly detected. In complete fistula occlusion, false
      positive findings were encountered on both T2-weighted images and on TOF MRA
      images. CONCLUSION: In this study, TR 3D MRA proved reliable in detecting DAVFs
      and suitable for follow-up imaging. The technique allowed--within limitations--to
      grade DAVFs. Although 3D TOF MRA can depict signs of DAVFs, its value for follow
      up imaging is limited.

PMID- 17494663
TI  - Endovascular treatment of epistaxis in patients with hereditary hemorrhagic
      telangiectasia.
AB  - BACKGROUND AND PURPOSE: The treatment of epistaxis in patients with hereditary
      hemorrhagic telangiectasia can be very challenging. The purpose of our study was
      to evaluate our experience with endovascular epistaxis embolization in patients
      with hemorrhagic hereditary telangiectasia and to compare this with our
      experience in patients treated for idiopathic epistaxis. MATERIALS AND METHODS:
      Over a 6-year period, we treated 22 patients with epistaxis by using endovascular
      embolization. Twelve of 22 patients had hereditary hemorrhagic telangiectasia; 10
      patients had idiopathic epistaxis. The angiographic findings, efficacy of
      treatment, and complications for both groups were compared. RESULTS: Patients
      with hereditary hemorrhagic telangiectasia had angiographic abnormalities in 92%
      of cases compared with only 30% in the idiopathic epistaxis group. Compared with
      a group of 10 patients treated for other causes of epistaxis, those with
      hereditary hemorrhagic telangiectasia required significantly more re-embolization
      treatments or additional surgical procedures because of continued or recurrent
      bleeding episodes after embolization (P=.03). Complications were rare; a single
      patient in the idiopathic epistaxis group had a self-limited groin hematoma and
      postembolization facial pain. CONCLUSION: Endovascular embolization of epistaxis
      is a safe procedure that can be useful for patients with severe acute epistaxis
      or chronic persistent bleeding. Patients who undergo endovascular embolization
      for epistaxis related to hereditary hemorrhagic telangiectasia require repeat
      embolization and subsequent surgical procedures more often than those with
      idiopathic epistaxis.

PMID- 17494664
TI  - Cisternography and ventriculography gadopentate dimeglumine-enhanced MR imaging
      in pediatric patients: preliminary report.
AB  - BACKGROUND AND PURPOSE: Complex CSF diseases may be underdiagnosed or poorly
      understood on conventional CT or MR imaging. Although intrathecal CT
      cisternography with water-soluble iodinated contrast medium has been used, very
      few studies have dealt with the intrathecal use of gadopentate dimeglumine (Gd
      DTPA), though it appears superior to CT. We report our experience with the
      intrathecal use of Gd-DTPA for MR cisternography and ventriculography in
      pediatric patients referred for study and treatment of complex CSF-related
      diseases. MATERIALS AND METHODS: Ten patients (range, 1 month-16 years of age)
      were selected after we obtained specific informed consent. Intrathecal gadolinium
      injection was performed via transfontanelle ventriculostomy, ventriculoperitoneal
      shunt reservoir, or lumbar puncture. Cases included spontaneous CSF leaks (n=1),
      complex traumatic frontoethmoidal fractures with suspected CSF leak (n=2),
      multiloculated congenital or acquired hydrocephalus (n=3), intraventricular tumor
      (n=1), suspected postoperative arachnoiditis (n=1), complex midline defect (n=1),
      and acquired orbital meningoencephalocele (n=1). RESULTS: No patient showed
      biologic, behavioral, or neurologic alterations. In complex hydrocephalus or
      intraventricular cysts, ventriculography Gd-DTPA MR imaging helped to
      differentiate isolation of a ventricle or noncommunicating cyst in all 4
      patients. In suspected posttraumatic CSF leaks, the procedure established with
      precision the place of the leak in 1 patient and excluded it in the other. In 1
      patient who underwent surgery for spinal cord neoplasm, the procedure excluded
      arachnoiditis. In the other 3 patients with complex CSF-related diseases, the
      procedure showed distinctive radiologic findings for the understanding and
      treatment of the disease. Altogether, in 8 patients, imaging findings influenced
      or changed clinical decisions and surgical planning. CONCLUSIONS: Our preliminary
      results showed no side effects and potential useful clinical applications in the
      evaluation of CNS diseases involving the ventricular system or the subarachnoid
      space in selected pediatric patients.

PMID- 17494665
TI  - Cerebral proton magnetic resonance spectroscopy in children with diabetic
      ketoacidosis.
AB  - BACKGROUND AND PURPOSE: Subclinical cerebral edema occurs in many, if not most,
      children with diabetic ketoacidosis (DKA) and may be an indicator of subtle brain
      injury. Brain ratios of N-acetylaspartate (NAA) to creatine (Cr), measured by
      proton MR spectroscopy, decrease with neuronal injury or dysfunction. We
      hypothesized that brain NAA/Cr ratios may be decreased in children in DKA,
      indicating subtle neuronal injury. MATERIALS AND METHODS: Twenty-nine children
      with DKA underwent cerebral proton MR spectroscopy during DKA treatment (2-12
      hours after initiating therapy) and after recovery from the episode (72 hours or
      more after the initiation of therapy). We measured peak heights of NAA, Cr, and
      choline (Cho) in 3 locations within the brain: the occipital gray matter, the
      basal ganglia, and periaqueductal gray matter. These regions were identified in
      previous studies as areas at greater risk for neurologic injury in DKA-related
      cerebral edema. We calculated the ratios of NAA/Cr and Cho/Cr and compared these
      ratios during the acute illness and recovery periods. RESULTS: In the basal
      ganglia, the ratio of NAA/Cr was significantly lower during DKA treatment
      compared with that after recovery (1.68 +/- 0.24 versus 1.86 +/- 0.28, P<.005).
      There was a trend toward lower NAA/Cr ratios during DKA treatment in the
      periaqueductal gray matter (1.66 +/- 0.38 versus 1.91 +/- 0.50, P=.06) and the
      occipital gray matter (1.97 +/- 0.28 versus 2.13 +/- 0.18, P=.08). In contrast,
      there were no significant changes in Cho/Cr ratios in any region. CONCLUSIONS:
      NAA/Cr ratios are decreased in children during DKA and improve after recovery.
      This finding suggests that during DKA neuronal function or viability or both are
      compromised and improve after treatment and recovery.

PMID- 17494666
TI  - Multimodality imaging of cortical and white matter abnormalities in Sturge-Weber
      syndrome.
AB  - BACKGROUND AND PURPOSE: Impaired cortical venous outflow and abnormal deep venous
      collaterals are common in Sturge-Weber syndrome (SWS), but their relation to
      brain metabolism and function is poorly understood. In this study, advanced MR
      imaging techniques, such as susceptibility-weighted imaging (SWI) and diffusion
      tensor imaging (DTI), were applied in conjunction with positron-emission
      tomography (PET), to assess cortical and white matter structural abnormalities
      and their relation to cortical glucose metabolism and cognitive functions in
      children with unilateral SWS. MATERIALS AND METHODS: Thirteen children (age, 1.5
      10.3 years) with unilateral SWS underwent MR imaging with SWI and DTI, glucose
      metabolism PET, and comprehensive neuropsychologic assessment prospectively. The
      MR imaging and PET images were coregistered and cortical regions showing
      decreased glucose metabolism were compared with locations of SWI signal intensity
      abnormalities, changes in white matter water diffusion, and cognitive functions.
      RESULTS: SWI detected both cortical abnormalities (n=8) and deep transmedullary
      veins (n=9), including those in young children with no cortical SWI signal
      intensity changes. These veins were often located under cortex adjacent to
      hypometabolic regions. DTI showed abnormal water diffusion both under
      hypometabolic cortex and in adjacent white matter with collateral veins.
      Cognitive dysfunction was associated with abnormal water diffusion in the
      posterior white matter. CONCLUSIONS: Transmedullary venous collaterals can be
      detected early by SWI and persist in white matter adjacent to damaged cortex in
      children with SWS. Microstructural white matter damage extends beyond cortical
      abnormalities and may contribute to cognitive impairment. SWI and DTI can be
      incorporated into clinical MR imaging acquisitions to objectively assess
      microstructural abnormalities at different stages of SWS.

PMID- 17494667
TI  - Proton MR spectroscopy and MRI-volumetry in mild traumatic brain injury.
AB  - BACKGROUND AND PURPOSE: More than 85% of brain traumas are classified as "mild";
      MR imaging findings are minimal if any and do not correspond to clinical
      symptoms. Our goal, therefore, was to quantify the global decline of the neuronal
      marker N-acetylaspartate (NAA), as well as gray (GM) and white matter (WM)
      atrophy after mild traumatic brain injury (mTBI). MATERIALS AND METHODS: Twenty
      patients (11 male, 9 female; age range, 19-57 years; median, 35 years) with mTBI
      (Glasgow Coma Scale score 13-15 with loss of consciousness for at least 30
      seconds) and 19 age- and sex-matched control subjects were studied. Seven
      patients were studied within 9 days of TBI; the other 13 ranged from 1.2 months
      to 31.5 years (average and median of 4.6 and 1.7 years, respectively) after
      injury. Whole-brain NAA (WBNAA) concentration was obtained in all subjects with
      nonlocalizing proton MR spectroscopy. Brain volume and GM and WM fractions were
      segmented from T1-weighted MR imaging and normalized to the total intracranial
      volume, suitable for intersubject comparisons. The data were analyzed with least
      squares regression. RESULTS: Patients with mTBI exhibited, on average, a 12%
      WBNAA deficit that increased with age, compared with the control subjects
      (p<.05). Adjusted for age effects, patients also suffered both global atrophy (
      1.09%/year; P=.029) and GM atrophy (-0.89%/year; P=.042). Patients with and
      without visible MR imaging pathology, typically punctate foci of suspected
      shearing injury, were indistinguishable in both atrophy and WBNAA. CONCLUSION:
      WBNAA detected neuronal/axonal injury beyond the minimal focal MR-visible lesions
      in mTBI. Combined with GM atrophy, the findings may provide further, noninvasive
      insight into the nature and progression of mTBI.

PMID- 17494668
TI  - Whole-brain N-acetylaspartate: a marker of the severity of mild head trauma.

PMID- 17494669
TI  - Relevance of common carotid intima-media thickness and carotid plaque as risk
      factors for ischemic stroke in patients with type 2 diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: An increase in the common carotid artery intima-media
      thickness (CCA-IMT) is generally considered an early marker of atherosclerosis.
      This cross-sectional study assessed the CCA-IMT and plaque score as vascular risk
      factors in patients with ischemic stroke and type 2 diabetes. MATERIALS AND
      METHODS: Brain MR imaging and carotid ultrasonography were performed in 133
      subjects with type 2 diabetes. IMT was measured at both CCAs. Differences in the
      variables between case and control subjects were compared statistically. To
      determine the independent factors related to CCA-IMT and plaque score, we
      performed stepwise multiple regression analysis. RESULTS: Sex, current smoking
      habit, history of hypertension, and high-density lipoprotein (HDL) levels
      differed significantly between the case and control groups. CCA-IMT and plaque
      score in patients with diabetes and acute ischemic stroke were significantly
      greater than in patients with diabetes who were stroke-free. The crude odds
      ratios suggested that CCA-IMT and plaque score are risk factors of acute ischemic
      stroke in patients with type 2 diabetes. However, when we adjusted for
      cerebrovascular risk factors, CCA-IMT and plaque score did not remain
      significantly associated with acute ischemic stroke. CONCLUSION: Increased CCA
      IMT and plaque score are associated with acute ischemic stroke in patients with
      type 2 diabetes. The higher CCA-IMT and plaque score found in ischemic stroke in
      patients with type 2 diabetes seem to be induced by cerebrovascular risk factors.
      Therefore, to prevent ischemic stroke in patients with type 2 diabetes, strict
      control of hyperglycemia, hypertension, smoking, and low HDL, together with
      monitoring of CCA-IMT and carotid plaque, may be important.

PMID- 17494670
TI  - CT angiography and diffusion-perfusion MR imaging in a patient with ipsilateral
      reversible cerebral vasoconstriction after carotid endarterectomy.
AB  - Reversible cerebral vasoconstriction syndromes (RCVS) typically affect the
      bilateral medium-sized intracerebral arteries and their branches. We describe a
      woman with RCVS restricted to the ipsilateral hemisphere after carotid
      endarterectomy. Serial CT angiography proved useful in documenting
      vasoconstriction. Perfusion MR imaging showed hypoperfusion in the deep watershed
      regions of the ipsilateral cerebral arteries but relatively normal perfusion in
      superficial cortical regions. Diffusion MR imaging showed progressive borderzone
      infarcts. These novel imaging findings provide insights into the pathophysiology
      of stroke in RCVS.

PMID- 17494671
TI  - Accuracy of pre- and postcontrast 3D time-of-flight MR angiography in patients
      with acute ischemic stroke: correlation with catheter angiography.
AB  - BACKGROUND AND PURPOSE: 3D time-of-flight (TOF) MR angiography (MRA) is
      insensitive to slow flow; however, the use of MR imaging contrast agents helps to
      visualize slow-flow vessels and avoids overestimation of vascular occlusion. The
      purpose of this study was to correlate pre- and postcontrast 3D TOF MRA with the
      results of conventional angiography during endovascular reperfusion therapy and
      to determine the accuracy of postcontrast 3D TOF MRA. MATERIALS AND METHODS:
      Thirteen patients who underwent endovascular reperfusion therapy for acute
      ischemic stroke were retrospectively analyzed. MR imaging techniques included
      single-slab 3D TOF MRA with and without contrast, as well as perfusion-weighted
      imaging. Angiography during reperfusion therapy was used as a standard of
      reference. Affected arteries were divided into segments either proximal or distal
      to the lesion, and pre- and postcontrast MRA signals were graded as absent,
      diminished or narrowed, or normal. RESULTS: In 2 of 5 patients with arterial
      stenosis and 6 of 8 patients with complete occlusion, MRA signal intensity
      proximal to each lesion was absent, indicating a proximal pseudo-occlusion on
      precontrast MRA. Postcontrast MRA demonstrated an arterial signal intensity
      proximal to the stenotic or occlusive lesions in all 13 patients. Arterial signal
      intensity distal to the occlusion was identified on postcontrast MRA in 7 of 8
      patients having complete occlusion, and the extent of occlusion on postcontrast
      MRA was similar to results of conventional angiography. CONCLUSION: In this small
      series, postcontrast 3D TOF MRA more accurately delineated the extent of stenotic
      or occlusive arterial lesions than precontrast MRA.

PMID- 17494672
TI  - Reproducibility of quantitative CT brain perfusion measurements in patients with
      symptomatic unilateral carotid artery stenosis.
AB  - BACKGROUND AND PURPOSE: To establish intraobserver and interobserver variability
      for regional measurement of CT brain perfusion (CTP) and to determine whether
      reproducibility can be improved by calculating perfusion ratios. MATERIALS AND
      METHODS: CTP images were acquired in 20 patients with unilateral symptomatic
      carotid artery stenosis (CAS). We manually drew regions of interest (ROIs) in the
      cortical flow territories of the anterior (ACA), middle (MCA), and posterior
      (PCA) cerebral arteries and the basal ganglia in each hemisphere; recorded
      cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time
      (MTT); and calculated ratios of perfusion values between symptomatic and
      asymptomatic hemisphere. We assessed intraobserver and interobserver variability
      by performing a Bland-Altman analysis of the relative differences between 2
      observations and calculated SDs of relative differences (SDD(rel)) as a measure
      of reproducibility. We used an F test to assess significance of differences
      between SDD(rel) of absolute CTP values and CTP ratios, and the Levine test to
      compare the 4 perfusion territories. RESULTS: MTT was the most reproducible
      parameter (SDD(rel) <or= 10%). Intraobserver and interobserver variability were
      higher for absolute CTP values compared with CTP ratios for CBV (16%-17% versus
      11%-16%) and CBF (18% versus 10%-13%) but not for MTT (5%-9%). Reproducibility
      was best in the MCA territory: SDD(rel) was <or=11% for perfusion ratios of all 3
      parameters. CONCLUSION: MTT is the most reproducible CTP parameter in patients
      with unilateral symptomatic CAS. Measurement variability in CBV and CBF can be
      improved if CTP ratios instead of CTP values are used. The MCA territory shows
      the least measurement variability.

PMID- 17494673
TI  - Analysis of central nervous system vasculitis with diffusion-weighted imaging and
      apparent diffusion coefficient mapping of the normal-appearing brain.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) is a novel method of
      studying the brain that creates tissue contrast secondary to water diffusion.
      Central nervous system (CNS) vasculitis is a rare inflammatory disease that
      continues to be difficult to diagnose and evaluate with MR imaging. DWI with
      apparent diffusion coefficient (ADC) analysis may demonstrate abnormalities
      within the brain that would otherwise be undetected by conventional imaging, thus
      aiding in the diagnosis and evaluation of patients with CNS vasculitis. MATERIALS
      AND METHODS: A retrospective analysis was performed of patients who were
      diagnosed with CNS vasculitis and had undergone DWI. A total of 15 patients who
      had DWI with b = 1000 were analyzed. Regions of interest were drawn in the
      anterior, central, and posterior regions of white matter (WM) at 3 levels.
      Regions of interest were also drawn bilaterally in the caudate heads, putamina,
      thalami, posterior internal capsules, and the cerebellar WM. ADC values were
      measured and compared with 15 healthy controls who were matched for age, sex, and
      MR imaging scanner. RESULTS: There was a significant increase in the ADC values
      (P<.00625) for the anterior WM, central WM, thalami, and posterior internal
      capsules in patients with CNS vasculitis. CONCLUSION: Diffuse increase in water
      diffusion was present in the normal-appearing brain in patients with CNS
      vasculitis, and these abnormalities were not demonstrated by conventional MR
      imaging sequences. The detection and quantification of ADC abnormalities may
      provide useful diagnostic information for patients with CNS vasculitis.

PMID- 17494674
TI  - Cerebral aneurysmal arteriopathy in an adult patient with acquired
      immunodeficiency syndrome.
AB  - In adult patients with acquired immunodeficiency syndrome (AIDS), cerebral
      arteritis usually takes the form of arterial wall thickening, stenosis, and
      occlusion, leading to cerebral ischemia and infarction. Aneurysms and
      intracranial hemorrhage are much less commonly associated with cerebral
      vasculitis. For reasons not entirely clear, this form is seen more often in
      pediatric patients infected with human immunodeficiency virus. We report an adult
      patient with cerebral aneurysmal arteriopathy who presented shortly after his
      AIDS-defining illness in a setting of severe immune suppression and high viral
      load.

PMID- 17494675
TI  - Cerebral venous thrombus signal intensity and susceptibility effects on gradient
      recalled-echo MR imaging.
AB  - BACKGROUND AND PURPOSE: Cerebral venous thrombus (CVT) signal intensity is
      variable on MR imaging, and the appearance of CVT on gradient recalled-echo (GRE)
      sequences has been incompletely assessed. This study was performed to evaluate
      the GRE imaging appearance of CVT in different stages of thrombus evolution and
      its relationship to signal intensity on other MR pulse sequences. MATERIALS AND
      METHODS: The clinical and MR imaging findings in 18 patients with CVT and GRE
      imaging were reviewed. Sixty-nine thrombosed venous segments were evaluated, and
      the signal intensity of thrombus relative to gray matter was determined. The
      degree of thrombus susceptibility effect (SE) was assessed and related to time of
      imaging after onset of symptoms (clinical thrombus age) and appearance on other
      pulse sequences. Segments were classified as SE+ (demonstrating susceptibility
      effect) or SE- (no susceptibility effect). RESULTS: Thirty-six venous segments
      exhibited visible SE. SE+ segments had a clinical thrombus age that was less than
      that in SE- segments (8.1 versus 24.6 days, P=.003). Sixty-three percent (23/36)
      of SE+ segments exhibited hypointensity on T2-weighted images (T2WI) versus 12%
      (4/33) of SE- segments (P<.001). Twenty-nine of 32 (90.6%) segments with clinical
      thrombus age of 0-7 days were SE+, versus 7 of 30 (23.3%) segments with a
      thrombus age of 8 days or greater. CONCLUSION: SEs from CVT can be detected with
      GRE imaging and are most prevalent in patients with hypointense thrombus on T2WI
      within 7 days after the symptom onset. This correlates with the paramagnetic
      effects of deoxyhemoglobin in acute stage thrombus. GRE imaging may be useful in
      detecting thrombus in this stage when difficult to detect on other pulse
      sequences.

PMID- 17494676
TI  - Diagnostic value of multidetector-row CT angiography in the evaluation of
      thrombosis of the cerebral venous sinuses.
AB  - BACKGROUND AND PURPOSE: The diagnosis of cerebral venous and sinus thrombosis
      (CVST) as a rare but important cause of stroke is challenging. We aimed to
      investigate the diagnostic value of multidetector-row CT angiography (MDCTA) as a
      fast and cost-effective imaging tool in diagnosing CVST. MATERIALS AND METHODS:
      Nineteen patients who presented with clinical symptoms of a possible CVST were
      included. All patients had received both MDCTA and MR imaging with venous MR
      angiography. Three blinded readers were asked to identify the cerebral sinuses
      and veins in MDCTA and to evaluate the presence of CVST in MDCTA. Consensus
      reading with interpretation of the MR imaging served to establish the definite
      diagnosis. RESULTS: The consensus reading revealed CVST in 10 of the 19 patients.
      With MDCTA, the venous sinuses could be identified in 99.2% and the cerebral
      veins in 87.6% of cases. The sensitivity and specificity of MDCTA for the
      diagnosis of CVST were 100%. CONCLUSION: Our study demonstrates that MDCTA
      provides excellent sensitivity and specificity for the diagnosis of CVST. Further
      studies are needed to evaluate the diagnostic potential of MDCTA in specific
      subsets of the general entity of CVST such as cortical venous thrombosis,
      thrombosis of the cavernous sinus, and thrombosis of the internal cerebral veins.

PMID- 17494677
TI  - Visualization of intracerebral arteries by synchrotron radiation
      microangiography.
AB  - BACKGROUND AND PURPOSE: Small cerebral vessels are a major site for vascular
      pathology leading to cerebral infarction and hemorrhage. However, such small
      cerebral vessels are difficult to visualize by using conventional methods. The
      goal of our study was the development of methodology allowing visualization of
      small cerebral arteries in rodents, suitable for experimental models. MATERIALS
      AND METHODS: Using barium sulfate as a contrast material, we obtained
      microangiographic images of physiologic and pathologic changes consequent to
      cerebral infarction in mouse brain by monochromatic synchrotron radiation (SR).
      To achieve high-resolution and high-contrast images, we used a new x-ray camera
      with a pixel size of 4.5 microm, and we set the energy level at 37.5 keV, just
      above the K absorption of barium. RESULTS: Small intracerebral arteries (
      approximately 30 microm in diameter) were clearly visualized, as well as the
      cortical branches (50-70 microm in diameter) at the brain surface. The limit of
      detection appeared to be vessels approximately 10 microm in diameter. Compared
      with the noninfarcted side, the number of intracerebral arteries was dramatically
      decreased in the middle cerebral artery area affected by stroke. CONCLUSIONS:
      These results indicate the potential of SR for evaluating pathologic changes in
      small cerebral arteries and for monitoring the impact of pro- and antiangiogenic
      therapeutic strategies.

PMID- 17494678
TI  - Diffusion tensor microscopy indicates the cytoarchitectural basis for diffusion
      anisotropy in the human hippocampus.
AB  - BACKGROUND AND PURPOSE: Observing changes to water diffusivity and fractional
      anisotropy (FA) for particular hippocampal regions may improve the sensitivity
      and specificity of diffusion tensor MR imaging for hippocampal pathologies like
      Alzheimer disease and mesial temporal sclerosis. As a first step toward this
      goal, this study characterized the cytoarchitectural features underlying
      diffusion anisotropy in human hippocampus autopsy specimens at 60-microm in-plane
      resolution. MATERIALS AND METHODS: Eight-millimeter coronal segments of the
      hippocampal body were dissected from 5 autopsy specimens (mean = 55.6 +/- 6.2
      years of age) with short postmortem intervals to fixation (21.2 +/- 5.7 hours)
      and no histologic evidence of neuropathology. Diffusion tensor microscopy data
      were collected from hippocampal specimens by using a 14.1T magnet with a protocol
      that included 21 unique diffusion gradient orientations (diffusion time = 17 ms,
      b = 1250 s/mm(2)). The resulting images were used to determine the mean
      diffusivity, FA, and principal fiber orientation for manually segmented
      hippocampal regions that included the stratum oriens, stratum radiatum, stratum
      pyramidale (CA1 and CA3), stratum lacunosum-molecular, hilus, molecular layer,
      granule cell layer, fimbria, and subiculum. RESULTS: Diffusion-weighted images
      had high signal-to-noise ratios (31.1 +/- 13.0) and delineated hippocampal
      anatomy well. Water diffusivity ranged from 1.21 +/- 0.22 x 10(-4) mm(2)/s in the
      fimbria to 3.48 +/- 0.72 x 10(-4) mm(2)/s in granule cells (analysis of variance,
      P<.001). Color fiber-orientation maps indicated the underlying microstructures
      responsible for diffusion anisotropy in the hippocampal lamina. CONCLUSION:
      Diffusion tensor microscopy provided novel microstructural information about the
      different lamina of the human hippocampus. These ex vivo data obtained at high
      magnetic-field strengths can be used to study injury-specific diffusion changes
      to susceptible hippocampal regions and may lead to more specific MR imaging
      surrogate markers for Alzheimer disease or epilepsy.

PMID- 17494679
TI  - Magnetization transfer ratio in Alzheimer disease: comparison with volumetric
      measurements.
AB  - BACKGROUND AND PURPOSE: Alzheimer disease (AD) is accompanied by macroscopic
      atrophy on volumetric MR imaging. A few studies have also demonstrated reduction
      in magnetization transfer ratio (MTR), suggesting microstructural changes in
      remaining brain tissue. This study assessed the value of measuring MTR in
      addition to volumetric MR in differentiating patients with AD from control
      subjects. MATERIALS AND METHODS: Volumetric T1-weighted images and 3D MTR maps
      were obtained from 18 patients with AD and 18 age-matched control subjects. Whole
      brain (WB) and total hippocampal (Hc) volumes were measured using semiautomated
      techniques and adjusted for total intracranial volume. Mean MTR was obtained for
      WB and in the Hc region. Histogram analysis was performed for WB MTR. Among
      patients, associations between volumetric and MTR parameters and the Mini-Mental
      State Examination (MMSE) were explored. RESULTS: Patients with AD had
      significantly reduced WB volume (P<.0001) and mean WB MTR (P=.002) and Hc volume
      (P<.0001) and Hc mean MTR (P<.0001) compared with control subjects. Histogram
      analysis of WB MTR revealed significant reduction in the 25th percentile point in
      patients with AD (P=.03). Both WB volume and mean MTR were independently
      associated with case-control status after adjusting for the other using linear
      regression models. However, measuring Hc mean MTR added no statistically
      significant discriminatory value over and above Hc volume measurement alone. Of
      all MR imaging parameters, only WB volume was significantly correlated with MMSE
      (r=0.47, P=.048). CONCLUSIONS: This study demonstrates the independent reduction
      of WB volume and mean MTR in AD. This suggests that the 2 parameters reflect
      complementary aspects of the AD pathologic lesion at macrostructural and
      microstructural levels.

PMID- 17494680
TI  - Idiopathic hypereosinophilic syndrome with skull base involvement.
AB  - Idiopathic hypereosinophilic syndrome (HES) is a heterogeneous disorder
      characterized by prolonged eosinophilia without an identifiable cause, ultimately
      resulting in organ dysfunction. Three major types of neurologic involvement have
      been well defined in HES; however, to our knowledge, inflammatory pseudotumor
      (IPT) in association with HES has not been reported. We present a case of IPT of
      the skull base in a patient with HES that suggests that HES may result in an
      exaggerated immunologic or inflammatory response leading to the formation of IPT.

PMID- 17494681
TI  - Lightning strike: a rare cause of bilateral ossicular disruption.
AB  - Otologic injury associated with fatal and nonfatal lightning strikes has been
      sporadically reported in the literature. The most common acoustic insult is a
      conductive hearing loss secondary to rupture of the tympanic membrane. Although
      conjecture has been made of the theoretic possibility of ossicular injury from
      lightning strike, to our knowledge, none has been demonstrated intraoperatively
      or postmortem. We report the first documented case of ossicular disruption in a
      lightning-strike victim.

PMID- 17494682
TI  - Cervical vertebral artery variations: an anatomic study.
AB  - In this article, we present 5 cases of uncommon anomalous vertebral arteries and
      discuss the possible embryologic etiologies. These cases include a left vertebral
      artery as the 2nd branch off the left subclavian, a left vertebral artery with 2
      origins, a right vertebral artery arising as the last branch off the aorta, a
      right vertebral artery arising as the 2nd branch off the right subclavian artery,
      and right vertebral artery with proximal duplication as the 2nd branch off the
      right subclavian artery.

PMID- 17494683
TI  - CT Features of an unusual calcified schwannoma of the superior laryngeal nerve.
AB  - We report the CT findings in a patient with a lateral neck mass histologically
      diagnosed as a laryngeal schwannoma but presenting some uncommon CT features. CT
      showed unusual calcified components, very rarely observed and potentially
      misleading for diagnosis. However, this imaging feature can be found in ancient
      schwannomas. Our case is, therefore, a very rare one and reviews the main
      differential diagnoses.

PMID- 17494684
TI  - Prediction of the jugular venous waveform using a model of CSF dynamics.
AB  - BACKGROUND AND PURPOSE: We have previously reported a model of cerebral
      hydrodynamics in the form of an equivalent electrical circuit. The aim of this
      work was to demonstrate that the model could predict venous flow patterns seen in
      the superior sagittal sinus (SSS), straight sinus (STS), and jugular vein (JV) in
      normal volunteers. MATERIALS AND METHODS: An electrical equivalence model of CSF
      and cerebral blood flow was fitted to measured arterial and CSF data from 16
      healthy volunteers. Predictions of the venous outflow waveform derived from the
      model were compared with measured venous flows in the SSS, STS, and JV. RESULTS:
      The model accurately predicted the measured jugular waveform. The measured
      waveforms from SSS and STS showed a less pronounced and delayed systolic peak
      compared with the predicted outflow. The fitted bulk model parameters provided
      relative values that correspond approximately to the impedance of arterial
      capillaries (1.0), cerebral aqueduct ( approximately 0), venous capillaries (
      approximately 0), and arteries (0.01) and for the elastic capacitance of the
      ventricles (4.11), capillaries ( approximately 0), and veins (271). The elastic
      capacitance of the major cerebral arteries was large and could not be accurately
      determined. CONCLUSIONS: We have confirmed the ability of the model to predict
      the venous waveforms in healthy persons. The absence of any statistically
      significant component of the venous waveform not described by the model implies
      that measurements of venous flow could be used to constrain further the model
      fitting process.

PMID- 17494685
TI  - Low back pain.

PMID- 17494686
TI  - Long-term, selective gene expression in developing and adult hippocampal
      pyramidal neurons using focal in utero electroporation.

PMID- 17494687
TI  - Distinct cis-regulatory elements from the Dlx1/Dlx2 locus mark different
      progenitor cell populations in the ganglionic eminences and different subtypes of
      adult cortical interneurons.
AB  - Distinct subtypes of cortical GABAergic interneurons provide inhibitory signals
      that are indispensable for neural network function. The Dlx homeobox genes have a
      central role in regulating their development and function. We have characterized
      the activity of three cis-regulatory sequences involved in forebrain expression
      of vertebrate Dlx genes: upstream regulatory element 2 (URE2), I12b, and I56i.
      The three regulatory elements display regional and temporal differences in their
      activities within the lateral ganglionic eminence (LGE), medial ganglionic
      eminence (MGE), and caudal ganglionic eminence (CGE) and label distinct
      populations of tangentially migrating neurons at embryonic day 12.5 (E12.5) and
      E13.5. We provide evidence that the dorsomedial and ventral MGE are distinct
      sources of tangentially migrating neurons during midgestation. In the adult
      cortex, URE2 and I12b/I56i are differentially expressed in parvalbumin-,
      calretinin-, neuropeptide Y-, and neuronal nitric oxide synthase-positive
      interneurons; I12b and I56i were specifically active in somatostatin-, vasoactive
      intestinal peptide-, and calbindin-positive interneurons. These data suggest that
      interneuron subtypes use distinct combinations of Dlx1/Dlx2 enhancers from the
      time they are specified through adulthood.

PMID- 17494688
TI  - Postnatal generation of neurons in the ventrobasal nucleus of the rat thalamus.
AB  - Most CNS systems, including the trigeminal-somatosensory system, develop via a
      hierarchical order (from the periphery and up the neuraxis). We tested the
      hypothesis that development of the trigeminal system can proceed via a
      nonhierarchical mechanism (i.e., that neuronogenesis can occur postnatally).
      Preweanling rats were perfused, and brain sections were stained with cresyl
      violet or immunolabeled with NeuN (for neuronal counts), or processed for
      acetylcholinesterase (AChE) activity or p75 immunoreactivity [to identify
      boundaries of the ventrobasal nucleus (VB)]. Neuronal number decreased during the
      first postnatal week but increased 2.5-fold over the next 3 weeks. To determine
      whether this remarkable rise resulted from the generation of new neurons,
      preweanlings were given injections of bromodeoxyuridine (BrdU) on postnatal day 6
      (P6) or P21. BrdU-positive VB cells were apparent on both days. Cumulative BrdU
      labeling showed that the cell cycle was 17.3 h on P6. Moreover, Ki-67, a protein
      elaborated throughout the cell cycle, was expressed by 25.8-29.3% of all VB cells
      on P6-P15, falling to 7.7% by P21. BrdU-positive VB cells coexpressed neuronal
      markers: NeuN, HuC/D, microtubule-associated protein 2, and a dextran placed in
      the somatosensory cortex. Note that postnatal neuronal generation was also
      evident in other thalamic nuclei (e.g., the lateral geniculate nucleus). Thus,
      the developing VB experiences two periods of neuronal generation. Prenatal
      neuronogenesis is part of hierarchical trigeminal-somatosensory development.
      Postnatal nonhierarchical neuronogenesis is intrathalamic and matches changes in
      neuromodulatory systems (exemplified by AChE activity and p75) and the arrival of
      corticothalamic afferents.

PMID- 17494689
TI  - Synaptic Ca2+ in darkness is lower in rods than cones, causing slower tonic
      release of vesicles.
AB  - Rod and cone photoreceptors use specialized biochemistry to generate light
      responses that differ in their sensitivity and kinetics. However, it is unclear
      whether there are also synaptic differences that affect the transmission of
      visual information. Here, we report that in the dark, rods tonically release
      synaptic vesicles at a much slower rate than cones, as measured by the release of
      the fluorescent vesicle indicator FM1-43. To determine whether slower release
      results from a lower Ca2+ sensitivity or a lower dark concentration of Ca2+, we
      imaged fluorescent indicators of synaptic vesicle cycling and intraterminal Ca2+.
      We report that the Ca2+ sensitivity of release is indistinguishable in rods and
      cones, consistent with their possessing similar release machinery. However, the
      dark intraterminal Ca2+ concentration is lower in rods than in cones, as
      determined by two-photon Ca2+ imaging. The lower level of dark Ca2+ ensures that
      rods encode intensity with a slower vesicle release rate that is better matched
      to the lower information content of dim light.

PMID- 17494690
TI  - Rhythmic episodes of subthreshold membrane potential oscillations in the rat
      inferior olive nuclei in vivo.
AB  - In vitro studies of inferior olive neurons demonstrate that they are
      intrinsically active, generating periodic spatiotemporal patterns. These self
      generated patterns of activity extend the role of olivary neurons beyond that of
      a deliverer of teaching or error signals. However, autorhythmicity or patterned
      activity of complex spikes in the cerebellar cortex was observed in only a few
      studies. This discrepancy between the self-generated rhythmicity in the inferior
      olive observed in vitro and the sporadic reports on rhythmicity of complex spikes
      can be reconciled by recording intracellularly from inferior olive neurons in
      situ. To this end, we recorded intracellularly from olivary neurons of
      anesthetized rats. We demonstrate that, in vivo, olivary neurons show both slow
      and fast rhythmic processes. The slow process (0.2-2 Hz) is expressed as rhythmic
      transitions from quiescent periods to periods of fast rhythm, manifested as
      subthreshold oscillations of 6-12 Hz. Spikes, if they occur, are locked to the
      depolarized phase of these subthreshold oscillations and, therefore, hold and
      transfer rhythmic information. The transient nature of these oscillatory epochs
      accounts for the difficulties to uncover them by prolonged recordings of complex
      spikes activity in the cerebellar cortex.

PMID- 17494691
TI  - Competitive integration of visual and preparatory signals in the superior
      colliculus during saccadic programming.
AB  - Efficient behavior requires that internally specified motor plans be integrated
      with incoming sensory information. Motor preparation and visual signals converge
      in the intermediate and deep layers of the superior colliculus (SC) to influence
      saccade planning and execution; however, the mechanism by which these sometimes
      conflicting signals are combined remains unclear. We studied this issue by
      presenting visual distractors as monkeys prepared saccades toward an upcoming
      target whose timing and location were fully predictable. Monkeys made more
      distractor-directed errors when the spatial location of visual distractors more
      closely coincided with the saccadic goal. Concomitant pretarget activity of SC
      visuomotor neurons, whose response fields were centered on the saccadic goal, was
      similarly increased by the presentation of nearby distractors and inhibited by
      the presentation of distant distractors. Finally, subthreshold microstimulation
      of the SC shifted the pattern of distractor-directed errors away from the
      saccadic goal toward that specified by the site of stimulation. Together, our
      results suggest that the likelihood of saccade generation is influenced by the
      spatial register of internal motor preparation signals and external sensory
      signals across the topographically organized SC map.

PMID- 17494692
TI  - Responses of neurons in primary visual cortex to transient changes in local
      contrast and luminance.
AB  - During normal saccadic inspection of natural images, the receptive fields of
      cortical neurons are bombarded with frequent simultaneous changes in local mean
      luminance and contrast, yet there have been no systematic studies of how cortical
      neurons respond to such stimulation. The responses of single neurons in the
      primary visual cortex of the cat were measured for 200 ms presentations of sine
      wave gratings confined to the conventional receptive field. Both local mean
      luminance and contrast were parametrically and randomly varied over the 1-1.5 log
      unit ranges that are typical of natural images. We find that responses are
      strongly modulated by both the local mean luminance and contrast, but in an
      approximately separable manner: the contrast response function is approximately
      invariant except for a scale factor that depends on the local mean luminance. The
      shape of the temporal response profiles were found to be approximately invariant
      with contrast, but were strongly affected by the local mean luminance. The
      results suggest that most, if not all, cortical neurons carry substantial local
      luminance information.

PMID- 17494693
TI  - Identification of compartment- and process-specific molecules required for
      "synaptic tagging" during long-term potentiation and long-term depression in
      hippocampal CA1.
AB  - Protein synthesis-dependent forms of hippocampal long-term potentiation (late
      LTP) and long-term depression (late LTD) are prominent cellular mechanisms
      underlying memory formation. Recent data support the hypothesis that neurons
      store relevant information in dendritic functional compartments during late LTP
      and late LTD rather than in single synapses. It has been suggested that processes
      of "synaptic tagging" are restricted to such functional compartments. Here, we
      show that in addition to apical CA1 dendrites, synaptic tagging also takes place
      within basal CA1 dendritic compartments after LTP induction. We present data that
      tagging in the basal dendrites is restricted to these compartments. Plasticity
      related proteins, partially nonspecific to the locally induced process, are
      synthesized in dendritic compartments and then captured by local, process
      specific synaptic tags. We support these findings in two ways: (1) late LTP/LTD,
      locally induced in apical or basal (late LTP) dendrites of hippocampal CA1
      neurons, does not spread to the basal or apical compartment, respectively; (2)
      the specificity of the synaptic plasticity event is achieved by the activation of
      process- and compartment-specific synaptic tag molecules. We have identified
      calcium/calmodulin-dependent protein kinase II as the first LTP-specific and
      extracellular signal-regulated kinase 1/2 as LTD-specific tag molecules in apical
      dendritic CA1 compartments, whereas either protein kinase A or protein kinase
      Mzeta mediates LTP-specific tags in basal dendrites.

PMID- 17494694
TI  - Defective retrotranslocation causes loss of anti-Bax function in human familial
      prion protein mutants.
AB  - Prion protein (PrP) inhibits the activation of proapoptotic Bax in primary human
      neurons and MCF-7 cells. Because neuronal apoptosis occurs in human prion
      diseases, here we examine the anti-Bax function of familial PrP mutants. All
      Creutzfeldt-Jakob disease and fatal familial insomnia-associated prion protein
      mutations partially or completely lose the anti-Bax function in human neurons
      and, except for A117V and V203I, in MCF-7 cells. The ability of the mutants to
      protect against Bax-mediated cell death is divided into three groups: (1) group
      I, retention of anti-Bax function in both the Val129 and Met129 mutants; (2)
      group II, retention of anti-Bax function only in Val129 mutants; and (3) group
      III, reduction or no anti-Bax function in Val129 and Met129 mutants. The loss of
      anti-Bax function in these PrP mutants correlates completely with a significant
      decrease in the production of cytosolic PrP, a form of PrP shown previously to
      have anti-Bax function in human neurons. Cotransfection of the full-length PrP
      mutants with wild-type or mutant cytosolic PrP, but not with wild type full
      length PrP, rescues the anti-Bax function of PrP. The results show that the
      failure of PrP mutants to produce cytosolic PrP is responsible for the loss of
      anti-Bax function and that the effect of the PrP mutants is dominant over wild
      type PrP. Furthermore, these results imply that misfolded PrP that escapes
      retrotranslocation could accumulate at the cell surface and cause neuronal
      dysfunction.

PMID- 17494695
TI  - Beta-arrestin2 and c-Src regulate the constitutive activity and recycling of mu
      opioid receptors in dorsal root ganglion neurons.
AB  - Beta-arrestins bind to agonist-activated G-protein-coupled receptors regulating
      signaling events and initiating endocytosis. In beta-arrestin2-/- (beta arr2-/-)
      mice, a complex phenotype is observed that includes altered sensitivity to
      morphine. However, little is known of how beta-arrestin2 affects mu receptor
      signaling. We investigated the coupling of mu receptors to voltage-gated Ca2+
      channels (VGCCs) in beta arr2+/+ and beta arr2-/- dorsal root ganglion neurons. A
      lack of beta-arrestin2 reduced the maximum inhibition of VGCCs by morphine and
      DAMGO (D-Ala2-N-Me-Phe4-glycol5-enkephalin) without affecting agonist potency,
      the onset of receptor desensitization, or the functional contribution of N-type
      VGCCs. The reduction in inhibition was accompanied by increased naltrexone
      sensitive constitutive inhibitory coupling of mu receptors to VGCCs. Agonist
      independent mu receptor inhibitory coupling was insensitive to CTAP (Cys-Tyr-D
      Trp-Arg-Thr-Pen-Thr-NH2), a neutral antagonist that inhibited the inverse agonist
      action of naltrexone. These functional changes were accompanied by diminished
      constitutive recycling and increased cell-surface mu receptor expression in beta
      arr2-/- compared with beta arr2+/+ neurons. Such changes could not be explained
      by the classical role of beta-arrestins in agonist-induced endocytosis. The
      localization of the nonreceptor tyrosine kinase c-Src appeared disrupted in beta
      arr2-/- neurons, and there was reduced activation of c-Src by DAMGO. Using the
      Src inhibitor PP2 [4-amino-5-(4-chlorophenyl)-(t-butyl)pyrazolo[3,4
      d]pyrimidine], we demonstrated that defective Src signaling mimics the beta arr2
      /- cellular phenotype of reduced mu agonist efficacy, increased constitutive mu
      receptor activity, and reduced constitutive recycling. We propose that beta
      arrestin2 is required to target c-Src to constitutively active mu receptors,
      resulting in their internalization, providing another dimension to the complex
      role of beta-arrestin2 and c-Src in G-protein-coupled receptor function.

PMID- 17494696
TI  - Encoding of movement fragments in the motor cortex.
AB  - Previous studies have suggested that complex movements can be elicited by
      electrical stimulation of the motor cortex. Most recording studies in the motor
      cortex, however, have investigated the encoding of time-independent features of
      movement such as direction, velocity, position, or force. Here, we show that
      single motor cortical neurons encode temporally evolving movement trajectories
      and not simply instantaneous movement parameters. We explicitly characterize the
      preferred trajectories of individual neurons using a simple exponential encoding
      model and demonstrate that temporally extended trajectories not only capture the
      tuning of motor cortical neurons more accurately, but can be used to decode the
      instantaneous movement direction with less error. These findings suggest that
      single motor cortical neurons encode whole movement fragments, which are
      temporally extensive and can be quite complex.

PMID- 17494697
TI  - CHIP overexpression reduces mutant androgen receptor protein and ameliorates
      phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease
      caused by the expansion of a polyglutamine tract within the androgen receptor
      (AR). The pathologic features of SBMA are motor neuron loss in the spinal cord
      and brainstem and diffuse nuclear accumulation and nuclear inclusions of the
      mutant AR in the residual motor neurons and certain visceral organs. Many
      components of the ubiquitin-proteasome and molecular chaperones are also
      sequestered in the inclusions, suggesting that they may be actively engaged in an
      attempt to degrade or refold the mutant AR. C terminus of Hsc70 (heat shock
      cognate protein 70)-interacting protein (CHIP), a U-box type E3 ubiquitin ligase,
      has been shown to interact with heat shock protein 90 (Hsp90) or Hsp70 and
      ubiquitylates unfolded proteins trapped by molecular chaperones and degrades
      them. Here, we demonstrate that transient overexpression of CHIP in a neuronal
      cell model reduces the monomeric mutant AR more effectively than it does the wild
      type, suggesting that the mutant AR is more sensitive to CHIP than is the wild
      type. High expression of CHIP in an SBMA transgenic mouse model also ameliorated
      motor symptoms and inhibited neuronal nuclear accumulation of the mutant AR. When
      CHIP was overexpressed in transgenic SBMA mice, mutant AR was also preferentially
      degraded over wild-type AR. These findings suggest that CHIP overexpression
      ameliorates SBMA phenotypes in mice by reducing nuclear-localized mutant AR via
      enhanced mutant AR degradation. Thus, CHIP overexpression would provide a
      potential therapeutic avenue for SBMA.

PMID- 17494698
TI  - EphA4 signaling regulates phospholipase Cgamma1 activation, cofilin membrane
      association, and dendritic spine morphology.
AB  - Specialized postsynaptic structures known as dendritic spines are the primary
      sites of glutamatergic innervation at synapses of the CNS. Previous studies have
      shown that spines rapidly remodel their actin cytoskeleton to modify their shape
      and this has been associated with changes in synaptic physiology. However, the
      receptors and signaling intermediates that restructure the actin network in
      spines are only beginning to be identified. We reported previously that the EphA4
      receptor tyrosine kinase regulates spine morphology. However, the signaling
      pathways downstream of EphA4 that induce spine retraction on ephrin ligand
      binding remain poorly understood. Here, we demonstrate that ephrin stimulation of
      EphA4 leads to the recruitment and activation of phospholipase Cgamma1
      (PLCgamma1) in heterologous cells and in hippocampal slices. This interaction
      occurs through an Src homology 2 domain of PLCgamma1 and requires the EphA4
      juxtamembrane tyrosines. In the brain, PLCgamma1 is found in multiple
      compartments of synaptosomes and is readily found in postsynaptic density
      fractions. Consistent with this, PLC activity is required for the maintenance of
      spine morphology and ephrin-induced spine retraction. Remarkably, EphA4 and PLC
      activity modulate the association of the actin depolymerizing/severing factor
      cofilin with the plasma membrane. Because cofilin has been implicated previously
      in the structural plasticity of spines, this signaling may enable cofilin to
      depolymerize actin filaments and restructure spines at sites of ephrin-EphA4
      contact.

PMID- 17494699
TI  - Experience improves feature extraction in Drosophila.
AB  - Previous exposure to a pattern in the visual scene can enhance subsequent
      recognition of that pattern in many species from honeybees to humans. However,
      whether previous experience with a visual feature of an object, such as color or
      shape, can also facilitate later recognition of that particular feature from
      multiple visual features is largely unknown. Visual feature extraction is the
      ability to select the key component from multiple visual features. Using a visual
      flight simulator, we designed a novel protocol for visual feature extraction to
      investigate the effects of previous experience on visual reinforcement learning
      in Drosophila. We found that, after conditioning with a visual feature of objects
      among combinatorial shape-color features, wild-type flies exhibited poor ability
      to extract the correct visual feature. However, the ability for visual feature
      extraction was greatly enhanced in flies trained previously with that visual
      feature alone. Moreover, we demonstrated that flies might possess the ability to
      extract the abstract category of "shape" but not a particular shape. Finally,
      this experience-dependent feature extraction is absent in flies with defective
      MBs, one of the central brain structures in Drosophila. Our results indicate that
      previous experience can enhance visual feature extraction in Drosophila and that
      MBs are required for this experience-dependent visual cognition.

PMID- 17494700
TI  - p75 neurotrophin receptor expression defines a population of BDNF-responsive
      neurogenic precursor cells.
AB  - Although our understanding of adult neurogenesis has increased dramatically over
      the last decade, confusion still exists regarding both the identity of the stem
      cell responsible for neuron production and the mechanisms that regulate its
      activity. Here we show, using flow cytometry, that a small population of cells
      (0.3%) within the stem cell niche of the rat subventricular zone (SVZ) expresses
      the p75 neurotrophin receptor (p75(NTR)) and that these cells are responsible for
      neuron production in both newborn and adult animals. In the adult, the p75(NTR)
      positive population contains all of the neurosphere-producing precursor cells,
      whereas in the newborn many of the precursor cells are p75(NTR) negative.
      However, at both ages, only the neurospheres derived from p75(NTR)-positive cells
      are neurogenic. We also show that neuron production from p75(NTR)-positive but
      not p75(NTR)-negative precursors is greatly enhanced after treatment with brain
      derived neurotrophic factor (BDNF) or nerve growth factor. This effect appears to
      be mediated specifically by p75(NTR), because precursor cells from p75(NTR)
      deficient mice show a 70% reduction in their neurogenic potential in vitro and
      fail to respond to BDNF treatment. Furthermore, adult p75(NTR)-deficient mice
      have significantly reduced numbers of PSA-NCAM (polysialylated neural cell
      adhesion molecule)-positive SVZ neuroblasts in vivo and a lower olfactory bulb
      weight. Thus, p75(NTR) defines a discrete population of highly proliferative SVZ
      precursor cells that are able to respond to neurotrophin activation by increasing
      neuroblast generation, making this pathway the most likely mechanism for the
      increased neurogenesis that accompanies raised BDNF levels in a variety of
      disease and behavioral situations.

PMID- 17494701
TI  - Multifunctional laryngeal premotor neurons: their activities during breathing,
      coughing, sneezing, and swallowing.
AB  - To examine whether motor commands of two or more distinct laryngeal motor
      patterns converge onto a common premotor network, we conducted dual recordings
      from the laryngeal adductor motoneuron and its premotor neuron within the
      brainstem respiratory circuitry during fictive breathing, coughing, sneezing, and
      swallowing in decerebrate paralyzed cats. Expiratory neurons with an augmenting
      firing pattern (EAUG), whose action potentials evoked monosynaptic IPSPs in the
      adductor motoneurons, sharply fired during the expulsive phases of fictive
      coughing and sneezing, during which the adductor motoneurons transiently
      repolarized. In contrast, these premotor neurons were silent during the swallow
      related hyperpolarization in adductor motoneurons. These results show that one
      class of medullary respiratory neuron, EAUG, is multifunctional and shared among
      the central pattern generators (CPGs) for breathing, coughing, and sneezing. In
      addition, although the CPGs underlying these three behaviors and the swallowing
      CPG do overlap, EAUG neurons are not part of the swallowing CPG and, in contrast
      to the other three behaviors, are not a source of inhibitory input to adductor
      motoneurons during swallowing.

PMID- 17494702
TI  - Selective cochlear degeneration in mice lacking the F-box protein, Fbx2, a
      glycoprotein-specific ubiquitin ligase subunit.
AB  - Little is known about the role of protein quality control in the inner ear. We
      now report selective cochlear degeneration in mice deficient in Fbx2, a ubiquitin
      ligase F-box protein with specificity for high-mannose glycoproteins (Yoshida et
      al., 2002). Originally described as a brain-enriched protein (Erhardt et al.,
      1998), Fbx2 is also highly expressed in the organ of Corti, in which it has been
      called organ of Corti protein 1 (Thalmann et al., 1997). Mice with targeted
      deletion of Fbxo2 develop age-related hearing loss beginning at 2 months.
      Cellular degeneration begins in the epithelial support cells of the organ of
      Corti and is accompanied by changes in cellular membrane integrity and early
      increases in connexin 26, a cochlear gap junction protein previously shown to
      interact with Fbx2 (Henzl et al., 2004). Progressive degeneration includes hair
      cells and the spiral ganglion, but the brain itself is spared despite widespread
      CNS expression of Fbx2. Cochlear Fbx2 binds Skp1, the common binding partner for
      F-box proteins, and is an unusually abundant inner ear protein. Whereas cochlear
      Skp1 levels fall in parallel with the loss of Fbx2, other components of the
      canonical SCF (Skp1, Cullin1, F-box, Rbx1) ubiquitin ligase complex remain
      unchanged and show little if any complex formation with Fbx2/Skp1, suggesting
      that cochlear Fbx2 and Skp1 form a novel, heterodimeric complex. Our findings
      demonstrate that components of protein quality control are essential for inner
      ear homeostasis and implicate Fbx2 and Skp1 as potential genetic modifiers in age
      related hearing loss.

PMID- 17494703
TI  - Changes in human muscle spindle sensitivity during a proprioceptive attention
      task.
AB  - The aim of the present study was to test whether fusimotor control of human
      muscle spindle sensitivity changed when attention was selectively directed to the
      recognition of an imposed two-dimensional movement in the form of a written
      symbol. The unitary activities of 32 muscle spindle afferents (26 Ia, 6 II) were
      recorded by microneurography at the level of the common peroneal nerve. The
      patterns of firing rate in response to passive movements of the ankle, forming
      different letters or numbers, were compared in two conditions: control and
      recognition. No visual cues were given in either condition, but subjects had to
      recognize and name the character in one condition compared with not paying
      attention in the control condition. The results showed that 58% of the tested Ia
      afferents presented modified responses to movements when these had to be
      recognized. Changes in Ia afferent responses included decreased depth of
      modulation, increased variability of discharge, and changes in spontaneous
      activity. Not all changes were evident in the same afferent. Furthermore, the
      percentage of correctly recognized movements amounted to 63% when changes were
      observed, but it was only 48% when the primary ending sensitivity was unaltered.
      The responses of group II afferents were only weakly changed or unchanged. It is
      suggested that the altered muscle spindle sensitivity is because of selective
      changes in fusimotor control, the consequence of which might be to feed the brain
      movement trajectory information that is more accurate.

PMID- 17494704
TI  - TRPC3 channels are necessary for brain-derived neurotrophic factor to activate a
      nonselective cationic current and to induce dendritic spine formation.
AB  - Brain-derived neurotrophic factor (BDNF) exerts prominent effects on hippocampal
      neurons, but the mechanisms that initiate its actions are poorly understood. We
      report here that BDNF evokes a slowly developing and sustained nonselective
      cationic current (I(BDNF)) in CA1 pyramidal neurons. These responses require
      phospholipase C, IP3 receptors, Ca2+ stores, and Ca2+ influx, suggesting the
      involvement of transient receptor potential canonical subfamily (TRPC) channels.
      Indeed, I(BDNF) is absent after small interfering RNA-mediated TRPC3 knockdown.
      The sustained kinetics of I(BDNF) appears to depend on phosphatidylinositol 3
      kinase-mediated TRPC3 membrane insertion, as shown by surface biotinylation
      assays. Slowly emerging membrane currents after theta burst stimulation are
      sensitive to the scavenger TrkB-IgG and TRPC inhibitors, suggesting I(BDNF)
      activation by evoked released of endogenous, native BDNF. Last, TRPC3 channels
      are necessary for BDNF to increase dendritic spine density. Thus, TRPC channels
      emerge as novel mediators of BDNF-mediated dendritic remodeling through the
      activation of a slowly developing and sustained membrane depolarization.

PMID- 17494705
TI  - Reversal of synaptic memory by Ca2+/calmodulin-dependent protein kinase II
      inhibitor.
AB  - Long-term potentiation (LTP) is an activity-dependent strengthening of synapses
      that is thought to underlie memory storage. Ca2+/calmodulin-dependent protein
      kinase II (CaMKII) has been a leading candidate as a memory molecule because it
      is persistently activated after LTP induction and can enhance transmission.
      Furthermore, a mutation that blocks persistent activation blocks LTP and forms of
      learning. However, direct evidence for a role of the kinase in maintaining
      synaptic strength has been lacking. Here, we show that a newly developed
      noncompetitive inhibitor of CaMKII strongly reduces synaptic transmission in the
      CA1 region of the hippocampal slice. This occurs through both presynaptic and
      postsynaptic action. To study the role of CaMKII in the maintenance of LTP,
      inhibitor was applied after LTP induction and then removed. Inhibition occurred
      in both LTP and control pathways but only partially recovered. The nonrecovering
      component was attributable primarily to a postsynaptic change. To test whether
      nonrecovery was attributable to a persistent reversal of LTP, we first saturated
      LTP and then transiently applied inhibitor. This procedure allowed additional LTP
      to be induced, indicating a reversal of an LTP maintenance mechanism. This is the
      first procedure that can reverse LTP by chemical means and suggests that a
      component of synaptic memory is attributable to CaMKII. The procedure also
      enhanced the LTP that could be induced in the control pathway, consistent with
      the idea that CaMKII is involved in controlling basal synaptic strength, perhaps
      as a result of LTP that occurred in vivo.

PMID- 17494706
TI  - Motorcortical excitability and synaptic plasticity is enhanced in professional
      musicians.
AB  - Musicians not only have extraordinary motor and sensory skills, but they also
      have an increased ability to learn new tasks compared with non-musicians. We
      examined how these features are expressed in neurophysiological parameters of
      excitability and plasticity in the motor system by comparing the results of 11
      professional musicians and 8 age-matched non-musicians. Parameters of motor
      excitability were assessed using transcranial magnetic stimulation (TMS) to
      measure motor-evoked potentials (MEPs) together with recruitment of corticospinal
      projections [input-output curve (IOcurve)] and of short-latency intracortical
      inhibition (SICIcurve). Plasticity, here defined as change of synaptic
      effectiveness, was tested by measuring MEPs and IOcurves after paired associative
      stimulation (PAS), which consists of an electric median nerve stimulus repeatedly
      paired (200 times at 0.25 Hz) with a TMS pulse over the hand motor area. Using an
      interstimulus interval of 25 ms (PAS25) or 10 ms (PAS10), this leads to long-term
      potentiation- or long-term depression-like plasticity, respectively. Musicians
      showed steeper recruitment of MEPs and SICI (IOcurve and SICIcurve).
      Additionally, PAS25 increased and PAS10 decreased the MEP amplitudes and the
      slope of the IOcurves significantly more in musicians than in non-musicians. This
      is consistent with a wider modification range of synaptic plasticity in
      musicians. Together with the steeper recruitment of corticospinal excitatory and
      intracortical inhibitory projections, this suggests that they regulate plasticity
      and excitability with a higher gain than normal. Because some of these changes
      depend on age at which instrumental playing commenced and on practice intensity,
      they may reflect an increase in number and modifiability of synapses within the
      motor area caused by long-term musical practice.

PMID- 17494707
TI  - Processing asymmetry of transitions between order and disorder in human auditory
      cortex.
AB  - Auditory environments vary as a result of the appearance and disappearance of
      acoustic sources, as well as fluctuations characteristic of the sources
      themselves. The appearance of an object is often manifest as a transition in the
      pattern of ongoing fluctuation, rather than an onset or offset of acoustic power.
      How does the system detect and process such transitions? Based on
      magnetoencephalography data, we show that the temporal dynamics and response
      morphology of the neural temporal-edge detection processes depend in precise ways
      on the nature of the change. We measure auditory cortical responses to
      transitions between "disorder," modeled as a sequence of random frequency tone
      pips, and "order," modeled as a constant tone. Such transitions embody key
      characteristics of natural auditory edges. Early cortical responses (from
      approximately 50 ms post-transition) reveal that order-disorder transitions, and
      vice versa, are processed by different neural mechanisms. Their dynamics suggest
      that the auditory cortex optimally adjusts to stimulus statistics, even when this
      is not required for overt behavior. Furthermore, this response profile bears a
      striking similarity to that measured from another order-disorder transition,
      between interaurally correlated and uncorrelated noise, a radically different
      stimulus. This parallelism suggests the existence of a general mechanism that
      operates early in the processing stream on the abstract statistics of the
      auditory input, and is putatively related to the processes of constructing a new
      representation or detecting a deviation from a previously acquired model of the
      auditory scene. Together, the data reveal information about the mechanisms with
      which the brain samples, represents, and detects changes in the environment.

PMID- 17494708
TI  - Interplay between laminar specificity and activity-dependent mechanisms of
      thalamocortical axon branching.
AB  - Target and activity-dependent mechanisms of axonal branching were studied in the
      thalamocortical (TC) projection using organotypic cocultures of the thalamus and
      cortex. TC axons were labeled with enhanced yellow fluorescent protein (EYFP) by
      a single-cell electroporation method and observed over time by confocal
      microscopy. Changes in the firing activity of cocultures grown on multielectrode
      dishes were also monitored over time. EYFP-labeled TC axons exhibited more branch
      formation in and around layer 4 of the cortical explant during the second week in
      vitro, when spontaneous firing activity increased in both thalamic and cortical
      cells. Time-lapse imaging further demonstrated that branching patterns were
      generated dynamically by addition and elimination with a bias toward branch
      accumulation in the target layer. To examine the relationship between neural
      activity and TC branch formation, the dynamics of axonal branching was analyzed
      under various pharmacological treatments. Chronic blockade of firing or synaptic
      activity reduced the remodeling process, in particular, branch addition in the
      target layer. However, extension of branches was not affected by this treatment.
      Together, these findings suggest that neural activity can modify the molecular
      mechanisms that regulate lamina-specific TC axon branching.

PMID- 17494709
TI  - Excitatory GABA action is essential for morphological maturation of cortical
      neurons in vivo.
AB  - GABA exerts excitatory actions on embryonic and neonatal cortical neurons, but
      the in vivo function of this GABA excitation is essentially unknown. Using in
      utero electroporation, we eliminated the excitatory action of GABA in a
      subpopulation of rat ventricular progenitors and cortical neurons derived from
      these progenitors by premature expression of the Cl- transporter KCC2, as
      confirmed by the changes in the reversal potential of GABA-induced currents and
      the resting membrane potential after GABA(A) receptor blockade. We found that
      radial migration to layer II/III of the somatosensory cortex of neurons derived
      from the transfected progenitors was not significantly affected, but their
      morphological maturation was markedly impaired. Furthermore, reducing neuronal
      excitability of cortical neurons in vivo by overexpressing an inward-rectifying
      K+ channel, which lowered the resting membrane potential, mimicked the effect of
      premature KCC2 expression. Thus, membrane depolarization caused by early GABA
      excitation is critical for morphological maturation of neonatal cortical neurons
      in vivo.

PMID- 17494710
TI  - Differential regulation of endogenous N- and P/Q-type Ca2+ channel inactivation
      by Ca2+/calmodulin impacts on their ability to support exocytosis in chromaffin
      cells.
AB  - P/Q-type (Ca(V)2.1) and N-type (Ca(V)2.2) Ca2+ channels are critical to stimulus
      secretion coupling in the nervous system; feedback regulation of these channels
      by Ca2+ is therefore predicted to profoundly influence neurotransmission. Here we
      report divergent regulation of Ca2+-dependent inactivation (CDI) of native N- and
      P/Q-type Ca2+ channels by calmodulin (CaM) in adult chromaffin cells. Robust CDI
      of N-type channels was observed in response to prolonged step depolarizations, as
      well as repetitive stimulation with either brief step depolarizations or action
      potential-like voltage stimuli. Adenoviral expression of Ca2+-insensitive
      calmodulin mutants eliminated CDI of N-type channels. This is the first
      demonstration of CaM-dependent CDI of a native N-type channel. CDI of P/Q-type
      channels was by comparison modest and insensitive to expression of CaM mutants.
      Cloning of the C terminus of the Ca(V)2.1 alpha1 subunit from chromaffin cells
      revealed multiple splice variants lacking structural motifs required for CaM
      dependent CDI. The physiological relevance of CDI on stimulus-coupled exocytosis
      was revealed by combining perforated-patch voltage-clamp recordings of
      pharmacologically isolated Ca2+ currents with membrane capacitance measurements
      of exocytosis. Increasing stimulus intensity to invoke CDI resulted in a
      significant decrease in the exocytotic efficiency of N-type channels compared
      with P/Q-type channels. Our results reveal unexpected diversity in CaM regulation
      of native Ca(V)2 channels and suggest that the ability of individual Ca2+ channel
      subtypes to undergo CDI may be tailored by alternative splicing to meet the
      specific requirements of a particular cellular function.

PMID- 17494711
TI  - Contribution of downregulation of L-type calcium currents to delayed neuronal
      death in rat hippocampus after global cerebral ischemia and reperfusion.
AB  - Transient forebrain ischemia induces delayed, selective neuronal death in the CA1
      region of the hippocampus. The underlying molecular mechanisms are as yet
      unclear, but it is known that activation of L-type Ca2+ channels specifically
      increases the expression of a group of genes required for neuronal survival.
      Accordingly, we examined temporal changes in L-type calcium-channel activity in
      CA1 and CA3 pyramidal neurons of rat hippocampus after transient forebrain
      ischemia by patch-clamp techniques. In vulnerable CA1 neurons, L-type Ca2+
      channel activity was persistently downregulated after ischemic insult, whereas in
      invulnerable CA3 neurons, no change occurred. Downregulation of L-type calcium
      channels was partially caused by oxidation modulation in postischemic channels.
      Furthermore, L-type but neither N-type nor P/Q-type Ca2+-channel antagonists
      alone significantly inhibited the survival of cultured hippocampal neurons. In
      contrast, specific L-type calcium-channel agonist remarkably reduced neuronal
      cell death and restored the inhibited channels induced by nitric oxide donor.
      More importantly, L-type calcium-channel agonist applied after reoxygenation or
      reperfusion significantly decreased neuronal injury in in vitro oxygen-glucose
      deprivation ischemic model and in animals subjected to forebrain ischemia
      reperfusion. Together, the present results suggest that ischemia-induced
      inhibition of L-type calcium currents may give rise to delayed death of neurons
      in the CA1 region, possibly via oxidation mechanisms. Our findings may lead to a
      new perspective on neuronal death after ischemic insult and suggest that a novel
      therapeutic approach, activation of L-type calcium channels, could be tested at
      late stages of reperfusion for stroke treatment.

PMID- 17494712
TI  - Mechanisms for synapse specificity during striatal long-term depression.
AB  - Endocannabinoid (eCB)-mediated forms of long-term synaptic plasticity occur in
      several brain regions, but much remains unknown about their basic properties and
      underlying mechanisms. Here, we present evidence that eCB-mediated long-term
      depression (eCB-LTD) at excitatory synapses on medium spiny neurons in the
      striatum requires presynaptic activity coincident with CB1 receptor activation.
      This dual requirement for CB1 activation and presynaptic activity is a mechanism
      by which eCB-LTD may be made synapse specific.

PMID- 17494713
TI  - Use of CultureSwab Plus swabs with Amies gel agar for testing of naris specimens
      with the GeneOhm MRSA assay.
AB  - The GeneOhm MRSA assay detects nasal colonization with methicillin-resistant
      Staphylococcus aureus (MRSA). We compared the use of seeded swabs with liquid
      Stuart's medium and that of seeded swabs with Amies gel for the assay. Overall,
      the swabs with liquid Stuart's medium detected significantly greater numbers of
      MRSA than the swabs with Amies gel (P = 0.0003).

PMID- 17494714
TI  - Multiple-locus variable-number tandem-repeat assay analysis of methicillin
      resistant Staphylococcus aureus strains.
AB  - Our objective was to determine if a multiple-locus variable-number tandem-repeat
      assay (MLVA) for Staphylococcus aureus could predict pulsed-field gel
      electrophoresis (PFGE) types (i.e., USA types), thus allowing us to replace PFGE
      with a simpler and more rapid typing method. One hundred three well-characterized
      isolates representing 13 major lineages of S. aureus were tested by both PFGE and
      MLVA. MLVA was performed using a rapid DNA extraction technique and PCR primers
      for sdrCDE, clfA, clfB, sspA, and spa. PFGE was performed with genomic DNA
      fragments generated using SmaI, as per CDC protocols. Banding patterns were
      analyzed both visually and with BioNumerics software. All isolates were typeable
      with MLVA and PFGE. MLVA patterns were highly reproducible. PFGE separated the
      isolates into 13 types with 42 subtypes. Using any band difference to designate a
      novel MLVA type, MLVA produced 45 types, including 9 clusters containing multiple
      isolates. Using BioNumerics and a cutoff of >75% relatedness, MLVA produced 28
      types, 11 of which contained >1 isolate. Epidemiologically related outbreak
      isolates of USA300-0114 from five states clustered in one MLVA pattern. USA100
      isolates were present in several unrelated (<40%) MLVA types. A cutoff of >80%
      separated outbreak strains of USA300-0114 into three distinct MLVA types. MLVA
      did not differentiate community methicillin-resistant S. aureus (MRSA) lineages
      (USA300, USA400, USA1000, and USA1100) from health care MRSA lineages (USA100,
      USA200, or USA500). The ability of MLVA to differentiate among strains that are
      indistinguishable by PFGE may be of epidemiologic value and warrants further
      study.

PMID- 17494715
TI  - Phenotypic prediction rule for community-associated methicillin-resistant
      Staphylococcus aureus.
AB  - Recent studies have suggested that community-associated methicillin-resistant
      Staphylococcus aureus (CA-MRSA) infections are encroaching upon nosocomial
      settings. We assessed the performance characteristics of a rule using the
      antimicrobial phenotype to predict genotype. This rule could be applied for
      epidemiologic purposes to describe the trend in CA-MRSA infections over time.

PMID- 17494716
TI  - Analysis of phenotypic variants of the serogroup C ET-15 clone of Neisseria
      meningitidis by pulsed-field gel electrophoresis.

PMID- 17494717
TI  - Comparative in vitro antimicrobial activity of tigecycline, a new glycylcycline
      compound, in freshly prepared medium and quality control.
AB  - The in vitro spectra of activity of tigecycline and tetracycline were determined
      for 2,490 bacterial isolates representing 50 different species or phenotypic
      groups. All isolates were tested simultaneously by broth microdilution using
      freshly prepared Mueller-Hinton broth and by disk diffusion. Portions of these
      data were submitted to the Food and Drug Administration (FDA) in support of the
      sponsor's application for new drug approval. In a separate study, MIC and disk
      diffusion quality control ranges were determined. The tigecycline MICs at which
      50%/90% of bacteria were inhibited were (in microg/ml) as follows: for
      Streptococcus spp., 0.06/0.12; for Moraxella catarrhalis, 0.06/0.12; for
      Staphylococcus spp., 0.12/0.25; for Enterococcus spp., 0.12/0.25; for Listeria
      monocytogenes, 0.12/0.12; for Neisseria meningitidis, 0.12/0.25; for Haemophilus
      spp., 0.25/0.5; for Enterobacteriaceae, 0.05/2.0; for non-Enterobacteriaceae,
      0.5/8.0. Tigecycline was consistently more potent than tetracycline against all
      species studied. The data from this study confirm the FDA-approved MIC and disk
      diffusion breakpoints for tigecycline for Streptococcus spp. other than
      Streptococcus pneumoniae, enterococci, and Enterobacteriaceae. Provisional
      breakpoints for Haemophilus spp. and S. pneumoniae are proposed based on the data
      from this study. The following MIC and/or disk diffusion quality control ranges
      are proposed: Staphylococcus aureus ATCC 29213, 0.03 to 0.25 microg/ml; S. aureus
      ATCC 25923, 20 to 25 mm; Escherichia coli ATCC 25922, 0.03 to 0.25 microg/ml and
      20 to 27 mm; Pseudomonas aeruginosa ATCC 27853, 9 to 13 mm, Enterococcus faecalis
      ATCC 29212, 0.03 to 0.12 microg/ml; S. pneumoniae ATCC 49619, 0.015 to 0.12
      microg/ml and 23 to 29 mm; Haemophilus influenzae ATCC 49247, 0.06 to 0.5
      microg/ml and 23 to 31 mm; and Neisseria gonorrhoeae ATCC 49226, 30 to 40 mm.

PMID- 17494718
TI  - Insertion sequence 1515 in the ply gene of a type 1 clinical isolate of
      Streptococcus pneumoniae abolishes pneumolysin expression.
AB  - A serotype 1 Streptococcus pneumoniae strain isolated by blood culture from a
      woman with pneumonia was found to harbor insertion sequence (IS) 1515 in the
      pneumolysin gene, abolishing pneumolysin expression. To our knowledge, this is
      the first report of an IS in the pneumolysin gene of S. pneumoniae.

PMID- 17494719
TI  - Legionella jordanis lower respiratory tract infection: case report and review.
AB  - Legionella jordanis was first described in 1982 after isolation from
      environmental sources and is otherwise a very rare human pathogen. Here, we
      report the recovery of L. jordanis from a bronchoalveolar lavage specimen from a
      patient who presented with an indolent lower respiratory tract infection
      associated with constitutional symptoms. This case is the first culture-positive
      case of infection involving this species in Canada.

PMID- 17494720
TI  - Comparison of various blood compartments and reporting units for the detection
      and quantification of Epstein-Barr virus in peripheral blood.
AB  - Epstein-Barr virus (EBV) infection is associated with a broad spectrum of
      disease. While quantification of EBV nucleic acid in the peripheral blood has
      been demonstrated to be useful for diagnosis and patient care, the optimal sample
      type and reporting format for such testing remain uncertain. Using quantitative
      real-time PCR (QRT-PCR), we evaluated EBV in whole blood (WB), peripheral blood
      mononuclear cells (PBMC), and plasma in 249 samples from 122 patients. In WB and
      PBMC, results were reported both in viral copies/ml and in copies/microg of total
      DNA. Trendings of quantitative values over time among the different sample types
      were compared. The sensitivities of QRT-PCR using WB and that using PBMC did not
      differ significantly (P = 0.33), and both were more sensitive than plasma alone
      (P < 0.0001). EBV viral load results from WB and PBMC paired sample types also
      showed a significant correlation (P < 0.05), as did results reported in copies/ml
      and copies/microg DNA for both WB and PBMC (R2 > 0.93). EBV viral loads detected
      using WB and PBMC trended very closely for the few patients who had multiple
      positive samples available for analysis. WB and PBMC show comparable
      sensitivities and a close quantitative correlation when assayed for EBV by QRT
      PCR. The close correlation between copies/ml and copies/microg DNA also suggests
      that normalization to cell number or genomic DNA in cellular specimens may not be
      necessary.

PMID- 17494721
TI  - Comparison of the Digene Hybrid Capture 2 assay and Roche AMPLICOR and LINEAR
      ARRAY human papillomavirus (HPV) tests in detecting high-risk HPV genotypes in
      specimens from women with previous abnormal Pap smear results.
AB  - The development of cervical cancer is strongly associated with the presence of
      persistent high-risk (HR) human papillomavirus (HPV) infection. Recently, the
      commercially manufactured PCR-based Roche AMPLICOR (AMP) and LINEAR ARRAY (LA)
      HPV tests have become available for HPV detection. However, knowledge of their
      clinical performance compared to the U.S. Food and Drug Administration-approved
      Hybrid Capture 2 (HC2) assay is limited. This study evaluated the concordance
      between the HC2, AMP, and LA tests in detecting HR-HPV among a cohort of 1,679
      women with previous abnormal Pap smear results. Overall, 1,393 specimens (81.3%)
      generated concordant results for HR-HPV presence or absence by the three assays.
      The concordance levels were substantial between the HC2 and AMP tests (84.4%,
      kappa = 0.6419) and between the HC2 and LA tests (84.0%, kappa = 0.6341) and
      nearly perfect between the AMP and LA tests (97.8%, kappa = 0.9441). HR-HPV
      prevalence, as detected by the AMP or LA tests, was significantly higher among
      women with cytological or histological high-grade disease (CIN2 or greater) than
      that detected by HC2 (P < 0.0001). The AMP and LA tests exhibited greater
      sensitivity, but lower specificity, than HC2 for detecting HR-HPV among this
      cohort of women with underlying cervical abnormalities, particularly among
      subjects with histologically proven high-grade disease. Both PCR-based HPV tests
      may be valuable in the management of care for women with underlying cervical
      abnormalities, in predicting treatment success, and in studying the clearance or
      acquisition of new infections.

PMID- 17494722
TI  - Diagnosis of a critical respiratory illness caused by human metapneumovirus by
      use of a pan-virus microarray.
AB  - A pan-virus DNA microarray (Virochip) was used to detect a human metapneumovirus
      (hMPV) strain associated with a critical respiratory tract infection in an
      elderly adult with chronic lymphocytic leukemia. This infection had previously
      eluded diagnosis despite extensive microbiological testing for possible etiologic
      agents. The patient's hMPV strain did not grow in viral culture, and only one of
      five specific reverse transcription-PCR assays for hMPV was positive.

PMID- 17494723
TI  - emm Types, virulence factors, and antibiotic resistance of invasive Streptococcus
      pyogenes isolates from Italy: What has changed in 11 years?
AB  - To investigate the epidemiology and characteristics of invasive group A
      streptococcal (GAS) disease over 11 years in Italy, this study compared the emm
      types and the superantigen toxin genes speA and speC as well as the erythromycin,
      clindamycin, and tetracycline susceptibilities of 207 invasive GAS strains
      collected during two national enhanced surveillance periods (1994 to 1996 and
      2003 to 2005) and the time between each set of surveillance periods. The present
      study demonstrated that emm1 strains were consistently responsible for about 20%
      of invasive GAS infections, while variations in the frequencies of the other
      types were noted, although the causes of most cases of invasive infections were
      restricted to emm1, emm3, emm4, emm6, emm12, and emm18. During the 1994 to 1996
      surveillance period, an emm89 epidemic clone spread across the northern part of
      Italy. A restricted macrolide resistance phenotype-type distribution of the
      bacteriophage-encoded speA toxin as well as of macrolide resistance genes was
      noted over time. Indeed, the recent acquisition of macrolide resistance in
      previously susceptible emm types was observed.

PMID- 17494724
TI  - An official ATS workshop report: issues in screening for asthma in children.

PMID- 17494725
TI  - Pathophysiology of dyspnea in chronic obstructive pulmonary disease: a
      roundtable.
AB  - Effective management of dyspnea in chronic obstructive pulmonary disease (COPD)
      requires a clearer understanding of its underlying mechanisms. This roundtable
      reviews what is currently known about the neurophysiology of dyspnea with the aim
      of applying this knowledge to the clinical setting. Dyspnea is not a single
      sensation, having multiple qualitative descriptors. Primary sources of dyspnea
      include: (1) inputs from multiple somatic proprioceptive and bronchopulmonary
      afferents, and (2) centrally generated signals related to inspiratory motor
      command output or effort. Respiratory disruption that causes a mismatch between
      medullary respiratory motor discharge and peripheral mechanosensor afferent
      feedback gives rise to a distressing urge to breathe which is independent of
      muscular effort. Recent brain imaging studies have shown increased limbic system
      activation in response to various dyspneogenic stimuli and emphasize the
      affective dimension of this symptom. All of these mechanisms are likely
      instrumental in exertional dyspnea causation in COPD. Increased central motor
      drive (and effort) is required to increase ventilation during activity because
      the inspiratory muscles become acutely overloaded and functionally weakened.
      Abnormal dynamic ventilatory mechanics and excessive chemostimulation during
      exercise also result in a widening disparity between escalating central neural
      drive and restricted thoracic volume displacement. This neuromechanical
      uncoupling may form the basis for the distressing sensation of unsatisfied
      inspiration. Interventions that alleviate dyspnea in COPD do so by improving
      ventilatory mechanics, reducing central neural drive, or both-thereby partially
      restoring neuromechanical coupling of the respiratory system. Self-management
      strategies address the affective aspect of dyspnea and are essential to
      successful treatment.

PMID- 17494726
TI  - Framing the forum: medical ethics in large-scale, interventional respiratory
      clinical trials.
AB  - Clinical research can create a conflict between the quest for science and the
      quest for individualized best patient care. The researcher must balance the
      degree of uncertainty about a particular treatment with the risk of patient
      exposure to control therapy. This is known as clinical equipoise. Clinical
      research and clinical care are intricately linked, yet they differ significantly
      from each other. This is an important distinction to make for both patients and
      physicians. This overview of ethics in clinical research will discuss some of the
      key contentious issues: informed consent (including payment for participation in
      a clinical trial, use of a placebo, and defining "standard of care"), research in
      critically ill patients, dissemination of study results, race issues, and
      financial disclosure. More research is being conducted by more investigators, in
      more organizations, in more disciplines than ever before. While this environment
      creates enormous opportunities for advances in healthcare, it also poses numerous
      challenges to the ethical conduct of clinical trials and raises numerous
      heretofore unconsidered issues.

PMID- 17494727
TI  - The Council for International Organizations and Medical Sciences (CIOMS)
      guidelines on ethics of clinical trials.
AB  - Numerous bodies from many countries, including governments, government regulatory
      departments, research organizations, medical professional bodies, and health care
      providers, have issued guidance or legislation on the ethical conduct of clinical
      trials. It is possible to trace the development of current guidelines back to the
      post-World War II Nuremburg war crimes trials, more specifically the "Doctors'
      Trial." From that trial emerged the Nuremburg Code, which set out basic
      principles to be observed when conducting research involving human subjects and
      which subsequently formed the basis for comprehensive international guidelines on
      medical research, such as the Declaration of Helsinki. Most recently, the Council
      for International Organizations and Medical Sciences (CIOMS) produced detailed
      guidelines (originally published in 1993 and updated in 2002) on the
      implementation of the principles outlined in the Declaration of Helsinki. The
      CIOMS guidelines set in an appropriate context the challenges of present-day
      clinical research, by addressing complex issues including HIV/AIDS research,
      availability of study treatments after a study ends, women as research subjects,
      safeguarding confidentiality, compensation for adverse events, as well guidelines
      on consent.

PMID- 17494728
TI  - Ethical issues during the conduct of clinical trials.
AB  - While the focus of ethical clinical trial conduct has been on protocol review in
      advance of the research, there has been a recent emphasis on monitoring subject
      welfare during the conduct of research. The ethical conduct of a clinical trial
      does not end with the formulation of study design or the obtainment of a
      signature on the informed consent form. This article defines and describes the
      necessary monitoring responsibilities to ensure the adequate protection of the
      rights and welfare of human subjects and the four parties who share such
      responsibilities: the institutional review board, the data monitoring committee
      (or the data safety and monitoring board), the sponsor, and the investigator.
      This article also reviews the numerous challenges associated with monitoring-
      such as overlapping responsibilities, communication gaps, and lack of standards-
      and attempts to provide recommendations to address some of these issues.

PMID- 17494729
TI  - Population issues in clinical trials.
AB  - Inclusion of underrepresented groups in clinical trials is important for several
      reasons. Age, sex, race, genetic factors, concomitant use of other medications,
      and comorbid conditions all may play pivotal roles in response to a drug or
      intervention. Despite the legislation for broader inclusion of underrepresented
      groups in clinical trials (via the National Institutes of Health [NIH]
      Revitalization Act of 1993), underrepresentation of particular populations,
      particularly minorities, continues to be a problem. Studies of predictors of
      clinical trial enrollment suggest that most people participate in clinical
      research to find relief from a disease, not for financial remuneration. Yet, men
      and whites are more likely to enroll in studies and some data indicate that
      certain patient populations are preferentially (albeit sometimes inadvertently)
      chosen for study enrollment. This tendency toward inclusion stems from human
      nature-the natural tendency for an investigator to relate to a particular
      investigative topic due to a special connection based on a cultural,
      socioeconomic, age, ethnicity, or gender level. This article reviews the most
      common population issues for clinical studies: age, gender, race, socioeconomic
      status, comorbidities, and disease severity, with examples of each from published
      studies. Recommendations are also offered to overcome these barriers.

PMID- 17494730
TI  - Informed consent, confidentiality, and subject rights in clinical trials.
AB  - The informed consent process is designed to inform the subject of the risks,
      rights, and benefits of participation in a clinical research trial. Informed
      consent, while not always necessary, is a critical component of ethical research
      involving human subjects. This article includes an overview of two sets of
      regulations regarding informed consent found in the Code of Federal Regulations
      (CFR) Titles 21 and 45: 21 CFR 50 and 56, the Food and Drug Administration
      Regulations, and 45 CFR 46, where applicable, the Department of Health and Human
      Services Regulations. Also included in this discussion are the general
      requirements of informed consent; challenging issues regarding informed consent;
      determining and obtaining informed consent in research involving vulnerable
      subjects (e.g., children, critically ill patients); the use of genetic
      information; confidentiality and privacy of subject information; and compensation
      for injury during a research study. Examples of acceptable and unacceptable
      (exculpatory) informed consent language are also provided as they may pertain to
      commercial gain, confidentiality, and compensation for injury. The goal of this
      article is to provide the clinical researcher with an explanation of the legal
      requirements for informed consent in clinical research. The researcher faces many
      challenges in implementing effective informed consent beyond the federal
      regulations.

PMID- 17494731
TI  - Ethical considerations in the interpretation and communication of clinical trial
      results.
AB  - The ethical interpretation and communication of research results is essential to
      ensure the validity, timeliness, and accessibility of new knowledge for patients,
      physicians, and regulatory agencies. Failure to adhere to ethical principles may
      cause adverse outcomes for patients because of overestimation of benefit,
      underestimation of harm, and lack of timely awareness of benefit or harm.
      Although fabrication, falsification, and plagiarism are the traditional criteria
      for research misconduct, other more subtle behaviors may cause greater threats to
      public safety and trust in the research enterprise. Growing awareness of research
      misconduct has led to a number of initiatives worldwide during the past decade in
      an attempt to control the problem at various stages of the research process
      through the funding agencies, research institutions, and editorial oversight. The
      objective of this article is to raise awareness among the pulmonary research
      community of the broad range of ethical issues that arise during manuscript
      preparation, review, publication, and dissemination of research results, and
      efforts that are in progress to minimize misconduct.

PMID- 17494732
TI  - Ethical issues confronted in pulmonary clinical trials.
AB  - Pulmonary clinical research possesses no unique ethical issues compared with
      other areas of medicine, but the range of disease states and conditions in
      pulmonary clinical research are broad. The ethical values guiding clinical
      research in pulmonary medicine are defined by the Belmont Report (i.e., patient
      autonomy, justice, and beneficence). This article uses some of the most well
      known clinical trials in pulmonary medicine to illustrate these issues and the
      numerous perspectives that must be considered. Ethical issues covered include
      introduction of new surgical procedures, placebo controls and drug withdrawal
      designs, smoking status in trials of patients with chronic obstructive pulmonary
      disease, and the tensions between community practice, clinical care guidelines,
      and evidence-based medicine.

PMID- 17494733
TI  - Evidence for regulatory function of nucleus-encoded factors on mRNA stabilization
      and translation in the chloroplast.
AB  - A salient feature of organelle gene expression is the requirement for nucleus
      encoded factors that act posttranscriptionally in a gene-specific manner. A
      central issue is to understand whether these factors are merely constitutive or
      have a regulatory function. In the unicellular alga Chlamydomonas reinhardtii,
      expression of the chloroplast petA gene-encoding cytochrome f, a major subunit of
      the cytochrome b(6)f complex, depends on two specific nucleus-encoded factors:
      MCA1, required for stable accumulation of the petA transcript, and TCA1, required
      for its translation. We cloned the TCA1 gene, encoding a pioneer protein, and
      transformed appropriate mutant strains with tagged versions of MCA1 and TCA1. In
      transformed strains expressing decreasing amounts of MCA1 or TCA1, the
      concentration of these factors proved limiting for petA mRNA accumulation and
      cytochrome f translation, respectively. This observation suggests that in
      exponentially growing cells, the abundance of MCA1 sets the pool of petA
      transcripts, some of which are TCA1-selected for an assembly-dependent
      translation of cytochrome f. We show that MCA1 is a short-lived protein. Its
      abundance varies rapidly with physiological conditions that deeply affect
      expression of the petA gene in vivo, for instance in aging cultures or upon
      changes in nitrogen availability. We observed similar but more limited changes in
      the abundance of TCA1. We conclude that in conditions where de novo biogenesis of
      cytochrome b(6)f complexes is not required, a rapid drop in MCA1 exhausts the
      pool of petA transcripts, and the progressive loss of TCA1 further prevents
      translation of cytochrome f.

PMID- 17494734
TI  - High-resolution physical and functional mapping of the template adjacent DNA
      binding site in catalytically active telomerase.
AB  - Telomerase is a cellular reverse transcriptase, which utilizes an integral RNA
      template to extend single-stranded telomeric DNA. We used site-specific
      photocrosslinking to map interactions between DNA primers and the catalytic
      protein subunit (tTERT) of Tetrahymena thermophila telomerase in functional
      enzyme complexes. Our assays reveal contact of the single-stranded DNA adjacent
      to the primer-template hybrid and tTERT residue W187 at the periphery of the N
      terminal domain. This contact was detected in complexes with three different
      registers of template in the active site, suggesting that it is maintained
      throughout synthesis of a complete telomeric repeat. Substitution of nearby
      residue Q168, but not W187, alters the K(m) for primer elongation, implying that
      it plays a role in the DNA recognition. These findings are the first to directly
      demonstrate the physical location of TERT-DNA contacts in catalytically active
      telomerase and to identify amino acid determinants of DNA binding affinity. Our
      data also suggest a movement of the TERT active site relative to the template
      adjacent single-stranded DNA binding site within a cycle of repeat synthesis.

PMID- 17494735
TI  - Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from
      human plasma.
AB  - Neutralizing antibodies directed against hepatitis C virus (HCV) are present in
      Igs made from anti-HCV-positive plasma. However, these HCV-specific Igs are
      largely ineffective in vivo. The mechanism for the poor effectiveness is
      currently unknown. We hypothesize that the presence of nonneutralizing antibodies
      in HCV-specific Igs interferes with the function of neutralizing antibodies,
      resulting in the reduction or blockage of their effect. In the present study, we
      identified at least two epitopes at amino acid residues 412-419 (epitope I) and
      434-446 (epitope II), located downstream of the hypervariable region I within the
      HCV E2 protein. We demonstrated that epitope I, but not epitope II, was
      implicated in HCV neutralization and that binding of a nonneutralizing antibody
      to epitope II completely disrupted virus neutralization mediated by antibody
      binding at epitope I. The dynamic interaction between nonneutralizing and
      neutralizing antibodies may thus play a key role in determining the outcomes of
      HCV infection. Further exploration of this interplay should lead to a better
      understanding of the mechanisms of neutralization and immune escape and may
      indicate pathways for the manufacture of an effective HCV-specific Ig product for
      immune prophylaxis of HCV infection.

PMID- 17494736
TI  - Evolution of nematode-trapping cells of predatory fungi of the Orbiliaceae based
      on evidence from rRNA-encoding DNA and multiprotein sequences.
AB  - Among fungi, the basic life strategies are saprophytism, parasitism, and
      predation. Fungi in Orbiliaceae (Ascomycota) prey on animals by means of
      specialized trapping structures. Five types of trapping devices are recognized,
      but their evolutionary origins and divergence are not well understood. Based on
      comprehensive phylogenetic analysis of nucleotide sequences of three protein
      coding genes (RNA polymerase II subunit gene, rpb2; elongation factor 1-alpha
      gene, ef1-alpha; and ss tubulin gene, bt) and ribosomal DNA in the internal
      transcribed spacer region, we have demonstrated that the initial trapping
      structure evolved along two lineages yielding two distinct trapping mechanisms:
      one developed into constricting rings and the other developed into adhesive
      traps. Among adhesive trapping devices, the adhesive network separated from the
      others early and evolved at a steady and gentle speed. The adhesive knob evolved
      through stalk elongation, with a final development of nonconstricting rings. Our
      data suggest that the derived adhesive traps are at a highly differentiated
      stage. The development of trapping devices is felicitous proof of adaptive
      evolution.

PMID- 17494737
TI  - Prandiology of Drosophila and the CAFE assay.
AB  - Studies of feeding behavior in genetically tractable invertebrate model systems
      have been limited by the lack of proper methodology. We introduce the Capillary
      Feeder (CAFE), a method allowing precise, real-time measurement of ingestion by
      individual or grouped fruit flies on the scale of minutes to days. Using this
      technique, we conducted the first quantitative analysis of prandial behavior in
      Drosophila melanogaster. Our results allow the dissection of feeding into
      discrete bouts of ingestion, defining two separate parameters, meal volume and
      frequency, that can be uncoupled and thus are likely to be independently
      regulated. In addition, our long-term measurements show that flies can ingest as
      much as 1.7x their body mass over 24 h. Besides the study of appetite, the CAFE
      can be used to monitor oral drug delivery. As an illustration, we used the CAFE
      to test the effects of dietary supplementation with two compounds, paraquat and
      ethanol, on food ingestion and preference. Paraquat, a prooxidant widely used in
      stress tests, had a strong anorexigenic effect. In contrast, in a feeding
      preference assay, ethanol-laced food, but not ethanol by itself, acted as an
      attractant.

PMID- 17494738
TI  - APEx 2-hybrid, a quantitative protein-protein interaction assay for antibody
      discovery and engineering.
AB  - We have developed a bacterial system for the discovery of interacting proteins
      that, unlike other two-hybrid technologies, allows for the selection of protein
      pairs on the basis of affinity or expression. This technology relies on the
      anchored periplasmic expression (APEx) of one protein (bait) on the periplasmic
      side of the inner membrane of Escherichia coli and its interacting partner (prey)
      as a soluble, epitope-tagged, periplasmic protein. Upon removal of the outer
      membrane by spheroplasting, periplasmic proteins, including any unbound epitope
      tagged prey, are released into the extracellular fluid. However, if the epitope
      tagged prey can bind to the membrane-anchored bait, it remains associated with
      the cell and can be detected quantitatively by using fluorescent anti-epitope tag
      antibodies. Cells expressing prey:bait pairs exhibiting different affinities can
      be readily distinguished by flow cytometry. The utility of this technology,
      called APEx two-hybrid, was demonstrated in two demanding antibody engineering
      applications: First, single-chain variable fragment (scFvs) with increased
      affinity to the protective antigen of Bacillus anthracis were isolated from cells
      coexpressing libraries of scFv random mutants, together with endogenously
      expressed antigen. Second, APEx two-hybrid coupled with multicolor FACS analysis
      to account for protein expression was used for the selection of mutant Fab
      antibody fragments exhibiting improved expression in the bacterial periplasm.

PMID- 17494739
TI  - Opening of connexin 43 hemichannels is increased by lowering intracellular redox
      potential.
AB  - Nonjunctional membrane in many cells contains connexin gap junction hemichannels
      (or connexons) that can open to allow permeation of small molecules. Opening of
      Cx43 hemichannels is infrequent in normal extracellular Ca(2+) and enhanced by
      low Ca(2+), positive membrane potentials, and dephosphorylation of critical
      residues. Here we report that lowering intracellular redox potential increases
      Cx43 hemichannel open probability under otherwise normal conditions. We studied
      dye uptake and single-channel activity in HeLa cells transfected with wild-type
      Cx43, Cx43 with enhanced GFP attached to its C terminus (Cx43-EGFP), and Cx43
      with enhanced GFP attached to its N terminus (EGFP-Cx43). Dithiothreitol [(DTT)
      10 mM], a membrane permeant-reducing agent, increased the rate of dye uptake by
      cells expressing Cx43 and Cx43-EGFP, but not by parental cells or cells
      expressing EGFP-Cx43. Induced dye uptake was blocked by La(3+), by a peptide gap
      junction and hemichannel blocker (gap 26), and by flufenamic acid. DTT increased
      Cx43-EGFP hemichannel opening at positive voltages. Bath application of reduced
      glutathione, a membrane impermeant-reducing agent, did not increase dye uptake,
      but glutathione in the recording pipette increased hemichannel opening at
      positive voltages, suggesting that it acted intracellularly. DTT caused little
      change in levels of surface Cx43 or Cx43-EGFP, or in intracellular pH. These
      findings suggest that lowering intracellular redox potential increases the
      opening of Cx43 and Cx43-EGFP hemichannels, possibly by action on cytoplasmic
      cysteine residues in the connexin C terminus.

PMID- 17494741
TI  - An experimental test of evolutionary trade-offs during temperature adaptation.
AB  - We used experimental evolution to test directly the important and commonplace
      evolutionary hypothesis that adaptation, increased fitness within the selective
      environment, is accompanied by trade-off, a loss of fitness in other nonselective
      environments. Specifically, we determined whether trade-offs at high temperature
      generally and necessarily accompany genetic adaptation to low temperature. We
      measured the relative fitness increment of 24 lineages of the bacterium
      Escherichia coli evolved for 2,000 generations at 20 degrees C and the relative
      fitness decrement of these lines at 40 degrees C. Trade-offs at the higher
      temperature were examined for their generality, universality, quantitative
      relationship, and historical contingency. Considering all 24 lines as a group, a
      significant decline in fitness was found at 40 degrees C (mean decline = 9.4%),
      indicating the generality of the trade-off effect. However, in a lineage-by
      lineage analysis, only 15 of 24 showed a significant trade-off, and one lineage
      increased fitness at high temperature. Thus, although general, trade-offs were
      not universal. Furthermore, there was no quantitative association between the
      magnitude of adaptive fitness increment at 20 degrees C and fitness decline at 40
      degrees C, and no effect of lineages' historical thermal environment on either
      their improvement at 20 degrees C or the extent of their trade-off at high
      temperature. We do not yet know the underlying mechanisms responsible for the
      trade-off, but they are sufficiently prevalent to drive a general effect.
      However, approximately one-third of the experimental lineages achieved low
      temperature adaptation without detectable high-temperature trade-offs; therefore,
      it cannot be necessary that every change conferring benefit in cold environments
      has a negative effect on function in warmer environments.

PMID- 17494740
TI  - The frailty of adaptive hypotheses for the origins of organismal complexity.
AB  - The vast majority of biologists engaged in evolutionary studies interpret
      virtually every aspect of biodiversity in adaptive terms. This narrow view of
      evolution has become untenable in light of recent observations from genomic
      sequencing and population-genetic theory. Numerous aspects of genomic
      architecture, gene structure, and developmental pathways are difficult to explain
      without invoking the nonadaptive forces of genetic drift and mutation. In
      addition, emergent biological features such as complexity, modularity, and
      evolvability, all of which are current targets of considerable speculation, may
      be nothing more than indirect by-products of processes operating at lower levels
      of organization. These issues are examined in the context of the view that the
      origins of many aspects of biological diversity, from gene-structural
      embellishments to novelties at the phenotypic level, have roots in nonadaptive
      processes, with the population-genetic environment imposing strong directionality
      on the paths that are open to evolutionary exploitation.

PMID- 17494742
TI  - From the Academy: Colloquium Perspective: In the light of evolution I: Adaptation
      and complex design.

PMID- 17494743
TI  - Full restoration of peripheral Foxp3+ regulatory T cell pool by radioresistant
      host cells in scurfy bone marrow chimeras.
AB  - Mutations in the gene encoding the transcription factor Foxp3 lead to fatal
      autoimmune pathology in mice and humans, which is associated with a deficiency in
      Foxp3(+) regulatory T cells (T(reg)). It has also been proposed that Foxp3
      inactivation in nonhematopoietic tissues, particularly in thymic epithelium, is
      required for the pathogenesis, because Foxp3 mutant scurfy bone marrow cells fail
      to transmit the disease to lethally irradiated WT hosts. We demonstrate here that
      the lack of pathology in these radiation chimeras is due to the presence of
      radioresistant endogenous Foxp3(+) T(reg) of the host. In addition, chimeras
      carrying the scurfy mutation only in nonhematopoietic cells exhibit no evidence
      of autoimmune pathology. Thus, Foxp3 deficiency in nonhematopoietic cells does
      not contribute to the scurfy disease. Furthermore, our analyses of radiation
      chimeras revealed that the peripheral T(reg) pool is fully and specifically
      restored and maintained by radioresistant endogenous T(reg) or adoptively
      transferred exogenous T(reg) through "homeostatic" proliferation in the absence
      of T(reg) production from scurfy donor bone marrow cells. These results thus
      provide evidence that the autoimmune pathology in scurfy mice results indeed from
      a T(reg) deficiency and illustrate a robust homeostatic mechanism that strictly
      controls the size of peripheral T(reg) pool by fine-tuning of homeostatic
      proliferation.

PMID- 17494744
TI  - Two routes to functional adaptation: Tibetan and Andean high-altitude natives.
AB  - Populations native to the Tibetan and Andean Plateaus are descended from
      colonizers who arrived perhaps 25,000 and 11,000 years ago, respectively. Both
      have been exposed to the opportunity for natural selection for traits that offset
      the unavoidable environmental stress of severe lifelong high-altitude hypoxia.
      This paper presents evidence that Tibetan and Andean high-altitude natives have
      adapted differently, as indicated by large quantitative differences in numerous
      physiological traits comprising the oxygen delivery process. These findings
      suggest the hypothesis that evolutionary processes have tinkered differently on
      the two founding populations and their descendents, with the result that the two
      followed different routes to the same functional outcome of successful oxygen
      delivery, long-term persistence and high function. Assessed on the basis of basal
      and maximal oxygen consumption, both populations avail themselves of essentially
      the full range of oxygen-using metabolism as populations at sea level, in
      contrast with the curtailed range available to visitors at high altitudes.
      Efforts to identify the genetic bases of these traits have included quantitative
      genetics, genetic admixture, and candidate gene approaches. These reveal
      generally more genetic variance in the Tibetan population and more potential for
      natural selection. There is evidence that natural selection is ongoing in the
      Tibetan population, where women estimated to have genotypes for high oxygen
      saturation of hemoglobin (and less physiological stress) have higher offspring
      survival. Identifying the genetic bases of these traits is crucial to discovering
      the steps along the Tibetan and Andean routes to functional adaptation.

PMID- 17494745
TI  - Functional information and the emergence of biocomplexity.
AB  - Complex emergent systems of many interacting components, including complex
      biological systems, have the potential to perform quantifiable functions.
      Accordingly, we define "functional information," I(E(x)), as a measure of system
      complexity. For a given system and function, x (e.g., a folded RNA sequence that
      binds to GTP), and degree of function, E(x) (e.g., the RNA-GTP binding energy),
      I(E(x)) = -log(2)[F(E(x))], where F(E(x)) is the fraction of all possible
      configurations of the system that possess a degree of function > or = E(x).
      Functional information, which we illustrate with letter sequences, artificial
      life, and biopolymers, thus represents the probability that an arbitrary
      configuration of a system will achieve a specific function to a specified degree.
      In each case we observe evidence for several distinct solutions with different
      maximum degrees of function, features that lead to steps in plots of information
      versus degree of function.

PMID- 17494747
TI  - Biological design in science classrooms.
AB  - Although evolutionary biology is replete with explanations for complex biological
      structures, scientists concerned about evolution education have been forced to
      confront "intelligent design" (ID), which rejects a natural origin for biological
      complexity. The content of ID is a subset of the claims made by the older
      "creation science" movement. Both creationist views contend that highly complex
      biological adaptations and even organisms categorically cannot result from
      natural causes but require a supernatural creative agent. Historically, ID arose
      from efforts to produce a form of creationism that would be less vulnerable to
      legal challenges and that would not overtly rely upon biblical literalism.
      Scientists do not use ID to explain nature, but because it has support from
      outside the scientific community, ID is nonetheless contributing substantially to
      a long-standing assault on the integrity of science education.

PMID- 17494746
TI  - The neoselectionist theory of genome evolution.
AB  - The vertebrate genome is a mosaic of GC-poor and GC-rich isochores, megabase
      sized DNA regions of fairly homogeneous base composition that differ in relative
      amount, gene density, gene expression, replication timing, and recombination
      frequency. At the emergence of warm-blooded vertebrates, the gene-rich,
      moderately GC-rich isochores of the cold-blooded ancestors underwent a GC
      increase. This increase was similar in mammals and birds and was maintained
      during the evolution of mammalian and avian orders. Neither the GC increase nor
      its conservation can be accounted for by the random fixation of neutral or nearly
      neutral single-nucleotide changes (i.e., the vast majority of nucleotide
      substitutions) or by a biased gene conversion process occurring at random genome
      locations. Both phenomena can be explained, however, by the neoselectionist
      theory of genome evolution that is presented here. This theory fully accepts
      Ohta's nearly neutral view of point mutations but proposes in addition (i) that
      the AT-biased mutational input present in vertebrates pushes some DNA regions
      below a certain GC threshold; (ii) that these lower GC levels cause regional
      changes in chromatin structure that lead to deleterious effects on replication
      and transcription; and (iii) that the carriers of these changes undergo negative
      (purifying) selection, the final result being a compositional conservation of the
      original isochore pattern in the surviving population. Negative selection may
      also largely explain the GC increase accompanying the emergence of warm-blooded
      vertebrates. In conclusion, the neoselectionist theory not only provides a
      solution to the neutralist/selectionist debate but also introduces an epigenomic
      component in genome evolution.

PMID- 17494748
TI  - Evolution of individuality during the transition from unicellular to
      multicellular life.
AB  - Individuality is a complex trait, yet a series of stages each advantageous in
      itself can be shown to exist allowing evolution to get from unicellular
      individuals to multicellular individuals. We consider several of the key stages
      involved in this transition: the initial advantage of group formation, the origin
      of reproductive altruism within the group, and the further specialization of cell
      types as groups increase in size. How do groups become individuals? This is the
      central question we address. Our hypothesis is that fitness tradeoffs drive the
      transition of a cell group into a multicellular individual through the evolution
      of cells specialized at reproductive and vegetative functions of the group. We
      have modeled this hypothesis and have tested our models in two ways. We have
      studied the origin of the genetic basis for reproductive altruism (somatic cells
      specialized at vegetative functions) in the multicellular Volvox carteri by
      showing how an altruistic gene may have originated through cooption of a life
      history tradeoff gene present in a unicellular ancestor. Second, we ask why
      reproductive altruism and individuality arise only in the larger members of the
      volvocine group (recognizing that high levels of kinship are present in all
      volvocine algae groups). Our answer is that the selective pressures leading to
      reproductive altruism stem from the increasing cost of reproduction with
      increasing group size. Concepts from population genetics and evolutionary biology
      appear to be sufficient to explain complexity, at least as it relates to the
      problem of the major transitions between the different kinds of evolutionary
      individuals.

PMID- 17494749
TI  - Adaptive evolution of color vision as seen through the eyes of butterflies.
AB  - Butterflies and primates are interesting for comparative color vision studies,
      because both have evolved middle- (M) and long-wavelength- (L) sensitive
      photopigments with overlapping absorbance spectrum maxima (lambda(max) values).
      Although positive selection is important for the maintenance of spectral
      variation within the primate pigments, it remains an open question whether it
      contributes similarly to the diversification of butterfly pigments. To examine
      this issue, we performed epimicrospectrophotometry on the eyes of five Limenitis
      butterfly species and found a 31-nm range of variation in the lambda(max) values
      of the L-sensitive photopigments (514-545 nm). We cloned partial Limenitis L
      opsin gene sequences and found a significant excess of replacement substitutions
      relative to polymorphisms among species. Mapping of these L photopigment
      lambda(max) values onto a phylogeny revealed two instances within Lepidoptera of
      convergently evolved L photopigment lineages whose lambda(max) values were blue
      shifted. A codon-based maximum-likelihood analysis indicated that, associated
      with the two blue spectral shifts, four amino acid sites (Ile17Met, Ala64Ser,
      Asn70Ser, and Ser137Ala) have evolved substitutions in parallel and exhibit
      significant d(N)/d(S) >1. Homology modeling of the full-length Limenitis arthemis
      astyanax L opsin placed all four substitutions within the chromophore-binding
      pocket. Strikingly, the Ser137Ala substitution is in the same position as a site
      that in primates is responsible for a 5- to 7-nm blue spectral shift. Our data
      show that some of the same amino acid sites are under positive selection in the
      photopigments of both butterflies and primates, spanning an evolutionary distance
      >500 million years.

PMID- 17494750
TI  - Insect societies as divided organisms: the complexities of purpose and cross
      purpose.
AB  - Individual organisms are complex in a special way. The organization and function
      of their parts seem directed toward a purpose: the survival and reproduction of
      that individual. Groups of organisms are different. They may also be complex, but
      that is usually because their parts, the individual organisms, are working at
      cross-purposes. The most obvious exception to this rule is the social insects.
      Here, the individuals cooperate in complex ways toward the common goal of the
      success of the colony, even if it means that most of them do not reproduce. Kin
      selection theory explains how this can evolve. Nonreproductive individuals help
      in the reproduction of their kin, who share and transmit their genes. Such help
      is most favored when individuals can give more to their kin than they give up by
      not reproducing directly. For example, they can remain at their natal site and
      help defend a valuable resource ("fortress defenders"), or they can ensure that
      at least one adult survives to care for helpless young ("life insurers").
      Although kin selection explains the extensive cooperation and common purpose of
      social insect colonies, it also predicts a certain amount of cross-purpose and
      conflict behavior. Kin selection has predicted how workers and queens disagree
      over sex ratios, how potential queens struggle to be the colony's head, how
      workers try to produce sons, and how other workers often prevent them. Kin
      selection analysis of cooperation and conflict in social insects is one of the
      outstanding achievements of evolutionary theory.

PMID- 17494751
TI  - On the origin and evolutionary diversification of beetle horns.
AB  - Many scarab beetles produce rigid projections from the body called horns. The
      exaggerated sizes of these structures and the staggering diversity of their forms
      have impressed biologists for centuries. Recent comparative studies using DNA
      sequence-based phylogenies have begun to reconstruct the historical patterns of
      beetle horn evolution. At the same time, developmental genetic experiments have
      begun to elucidate how beetle horns grow and how horn growth is modulated in
      response to environmental variables, such as nutrition. We bring together these
      two perspectives to show that they converge on very similar conclusions regarding
      beetle evolution. Horns do not appear to be difficult structures to gain or lose,
      and they can diverge both dramatically and rapidly in form. Although much of this
      work is still preliminary, we use available information to propose a conceptual
      developmental model for the major trajectories of beetle horn evolution. We
      illustrate putative mechanisms underlying the evolutionary origin of horns and
      the evolution of horn location, shape, allometry, and dimorphism.

PMID- 17494752
TI  - Profiling signaling polarity in chemotactic cells.
AB  - Cell movement requires morphological polarization characterized by formation of a
      leading pseudopodium (PD) at the front and a trailing rear at the back. However,
      little is known about how protein networks are spatially integrated to regulate
      this process at the system level. Here, we apply global proteome profiling in
      combination with newly developed quantitative phosphoproteomics approaches for
      comparative analysis of the cell body (CB) and PD proteome of chemotactic cells.
      The spatial relationship of 3,509 proteins and 228 distinct sites of
      phosphorylation were mapped revealing networks of signaling proteins that
      partition to the PD and/or the CB compartments. The major network represented in
      the PD includes integrin signaling, actin regulatory, and axon guidance proteins,
      whereas the CB consists of DNA/RNA metabolism, cell cycle regulation, and
      structural maintenance. Our findings provide insight into the spatial
      organization of signaling networks that control cell movement and provide a
      comprehensive system-wide profile of proteins and phosphorylation sites that
      control cell polarization.

PMID- 17494753
TI  - Darwin's greatest discovery: design without designer.
AB  - Darwin's greatest contribution to science is that he completed the Copernican
      Revolution by drawing out for biology the notion of nature as a system of matter
      in motion governed by natural laws. With Darwin's discovery of natural selection,
      the origin and adaptations of organisms were brought into the realm of science.
      The adaptive features of organisms could now be explained, like the phenomena of
      the inanimate world, as the result of natural processes, without recourse to an
      Intelligent Designer. The Copernican and the Darwinian Revolutions may be seen as
      the two stages of the one Scientific Revolution. They jointly ushered in the
      beginning of science in the modern sense of the word: explanation through natural
      laws. Darwin's theory of natural selection accounts for the "design" of
      organisms, and for their wondrous diversity, as the result of natural processes,
      the gradual accumulation of spontaneously arisen variations (mutations) sorted
      out by natural selection. Which characteristics will be selected depends on which
      variations happen to be present at a given time in a given place. This in turn
      depends on the random process of mutation as well as on the previous history of
      the organisms. Mutation and selection have jointly driven the marvelous process
      that, starting from microscopic organisms, has yielded orchids, birds, and
      humans. The theory of evolution conveys chance and necessity, randomness and
      determinism, jointly enmeshed in the stuff of life. This was Darwin's fundamental
      discovery, that there is a process that is creative, although not conscious.

PMID- 17494754
TI  - Between "design" and "bricolage": genetic networks, levels of selection, and
      adaptive evolution.
AB  - The extent to which "developmental constraints" in complex organisms restrict
      evolutionary directions remains contentious. Yet, other forms of internal
      constraint, which have received less attention, may also exist. It will be argued
      here that a set of partial constraints below the level of phenotypes, those
      involving genes and molecules, influences and channels the set of possible
      evolutionary trajectories. At the top-most organizational level there are the
      genetic network modules, whose operations directly underlie complex morphological
      traits. The properties of these network modules, however, have themselves been
      set by the evolutionary history of the component genes and their interactions.
      Characterization of the components, structures, and operational dynamics of
      specific genetic networks should lead to a better understanding not only of the
      morphological traits they underlie but of the biases that influence the
      directions of evolutionary change. Furthermore, such knowledge may permit
      assessment of the relative degrees of probability of short evolutionary
      trajectories, those on the microevolutionary scale. In effect, a "network
      perspective" may help transform evolutionary biology into a scientific enterprise
      with greater predictive capability than it has hitherto possessed.

PMID- 17494755
TI  - The theory of facilitated variation.
AB  - This theory concerns the means by which animals generate phenotypic variation
      from genetic change. Most anatomical and physiological traits that have evolved
      since the Cambrian are, we propose, the result of regulatory changes in the usage
      of various members of a large set of conserved core components that function in
      development and physiology. Genetic change of the DNA sequences for regulatory
      elements of DNA, RNAs, and proteins leads to heritable regulatory change, which
      specifies new combinations of core components, operating in new amounts and
      states at new times and places in the animal. These new configurations of
      components comprise new traits. The number and kinds of regulatory changes needed
      for viable phenotypic variation are determined by the properties of the
      developmental and physiological processes in which core components serve, in
      particular by the processes' modularity, robustness, adaptability, capacity to
      engage in weak regulatory linkage, and exploratory behavior. These properties
      reduce the number of regulatory changes needed to generate viable selectable
      phenotypic variation, increase the variety of regulatory targets, reduce the
      lethality of genetic change, and increase the amount of genetic variation
      retained by a population. By such reductions and increases, the conserved core
      processes facilitate the generation of phenotypic variation, which selection
      thereafter converts to evolutionary and genetic change in the population. Thus,
      we call it a theory of facilitated phenotypic variation.

PMID- 17494756
TI  - Low-intensity transplant regimens facilitate recruitment of donor-specific
      regulatory T cells that promote hematopoietic engraftment.
AB  - Low- or reduced-intensity conditioning regimens for allogeneic hemopoietic stem
      cell transplantation are effective at establishing donor hematopoietic
      engraftment and host-vs.-graft (HvG) tolerance. We investigated the mechanisms of
      HvG tolerance induction and maintenance in an animal model in which
      transplantation of sublethally irradiated female recipients with bone marrow (BM)
      from syngeneic male donors produces mixed chimerism. Splenocytes from chimeric
      mice inhibited HY-specific CD8(+) T cell responses both in vitro and in vivo, and
      their adoptive transfer facilitated donor hematopoietic engraftment. These
      properties were contained within the CD4(+)CD25(+) population. The conditioning
      protocol alone led to a proportional expansion of regulatory T cells (T(regs)),
      but the inhibitory activity was induced only if male BM was infused. The
      administration of anti-CD25-depleting antibodies to conditioned recipients at
      time of BM transplantation prevented donor-recipient chimerism but did not affect
      engraftment if performed after the establishment of chimerism, thus indicating
      that recipient T(regs) are required for the generation but not the maintenance of
      HvG tolerance. We conclude that donor-specific T(regs) of recipient origin are
      recruited when the donor antigens are present during reduced-intensity
      conditioning-induced T(reg) expansion.

PMID- 17494757
TI  - Plant domestication, a unique opportunity to identify the genetic basis of
      adaptation.
AB  - Despite the fundamental role of plant domestication in human history and the
      critical importance of a relatively small number of crop plants to modern
      societies, we still know little about adaptation under domestication. Here we
      focus on efforts to identify the genes responsible for adaptation to
      domestication. We start from a historical perspective, arguing that Darwin's
      conceptualization of domestication and unconscious selection provides valuable
      insight into the evolutionary history of crops and also provides a framework to
      evaluate modern methods used to decipher the genetic mechanisms underlying
      phenotypic change. We then review these methods, framing the discussion in terms
      of the phenotype-genotype hierarchy. Top-down approaches, such as quantitative
      trait locus and linkage disequilibrium mapping, start with a phenotype of
      interest and use genetic analysis to identify candidate genes. Bottom-up
      approaches, alternatively, use population genetic analyses to identify
      potentially adaptive genes and then rely on standard bioinformatics and reverse
      genetic tools to connect selected genes to a phenotype. We discuss the successes,
      advantages, and challenges of each, but we conclude that bottom-up approaches to
      understanding domestication as an adaptive process hold greater promise both for
      the study of adaptation and as a means to identify genes that contribute to
      agronomically important traits.

PMID- 17494758
TI  - Platelet glycoprotein Ib alpha supports experimental lung metastasis.
AB  - The platelet paradigm in hemostasis and thrombosis involves an initiation step
      that depends on platelet membrane receptors binding to ligands on a damaged or
      inflamed vascular surface. Once bound to the surface, platelets provide a unique
      microenvironment supporting the accumulation of more platelets and the
      elaboration of a fibrin-rich network produced by coagulation factors. The
      platelet-specific receptor glycoprotein (GP) Ib-IX, is critical in this process
      and initiates the formation of a platelet-rich thrombus by tethering the platelet
      to a thrombogenic surface. A role for platelets beyond the hemostasis/thrombosis
      paradigm is emerging with significant platelet contributions in both
      tumorigenesis and inflammation. We have established congenic (N10) mouse colonies
      (C57BL/6J) with dysfunctional GP Ib-IX receptors in our laboratory that allow us
      an opportunity to examine the relevance of platelet GP Ib-IX in syngeneic mouse
      models of experimental metastasis. Our results demonstrate platelet GP Ib-IX
      contributes to experimental metastasis because a functional absence of GP Ib-IX
      correlates with a 15-fold reduction in the number of lung metastatic foci using
      B16F10.1 melanoma cells. The results demonstrate that the extracellular domain of
      the alpha-subunit of GP Ib is the structurally relevant component of the GP Ib-IX
      complex contributing to metastasis. Our results support the hypothesis that
      platelet GP Ib-IX functions that support normal hemostasis or pathologic
      thrombosis also contribute to tumor malignancy.

PMID- 17494759
TI  - Emerging principles of regulatory evolution.
AB  - Understanding the genetic and molecular mechanisms governing the evolution of
      morphology is a major challenge in biology. Because most animals share a
      conserved repertoire of body-building and -patterning genes, morphological
      diversity appears to evolve primarily through changes in the deployment of these
      genes during development. The complex expression patterns of developmentally
      regulated genes are typically controlled by numerous independent cis-regulatory
      elements (CREs). It has been proposed that morphological evolution relies
      predominantly on changes in the architecture of gene regulatory networks and in
      particular on functional changes within CREs. Here, we discuss recent
      experimental studies that support this hypothesis and reveal some unanticipated
      features of how regulatory evolution occurs. From this growing body of evidence,
      we identify three key operating principles underlying regulatory evolution, that
      is, how regulatory evolution: (i) uses available genetic components in the form
      of preexisting and active transcription factors and CREs to generate novelty;
      (ii) minimizes the penalty to overall fitness by introducing discrete changes in
      gene expression; and (iii) allows interactions to arise among any transcription
      factor and downstream CRE. These principles endow regulatory evolution with a
      vast creative potential that accounts for both relatively modest morphological
      differences among closely related species and more profound anatomical
      divergences among groups at higher taxonomical levels.

PMID- 17494760
TI  - Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via
      androgen receptor tyrosine phosphorylation.
AB  - Activation of the androgen receptor (AR) may play a role in androgen-independent
      progression of prostate cancer. Multiple mechanisms of AR activation, including
      stimulation by tyrosine kinases, have been postulated. We and others have
      recently shown involvement of activated Cdc42-associated tyrosine kinase Ack1 in
      advanced human prostate cancer. Here we provide the molecular basis for interplay
      between Ack1 and AR in prostate cancer cells. Activated Ack1 promoted androgen
      independent growth of LNCaP and LAPC-4 prostate xenograft tumors, AR recruitment
      to the androgen-responsive enhancer, and androgen-inducible gene expression in
      the absence of androgen. Heregulin-stimulated HER2 activation induced Ack1
      activation and AR tyrosine phosphorylation. Ack1 knockdown inhibited heregulin
      dependent AR tyrosine phosphorylation, AR reporter activity, androgen-stimulated
      gene expression, and AR recruitment. Ack1 was recruited to the androgen
      responsive enhancers after androgen and heregulin stimulation. In 8 of 18 primary
      androgen-independent prostate tumor samples, tyrosine-phosphorylated AR protein
      was detected and correlated with the detection of tyrosine-phosphorylated Ack1.
      Neither was elevated in androgen-dependent tumors or benign prostate samples.
      Activated Ack1 phosphorylated AR protein at Tyr-267 and Tyr-363, both located
      within the transactivation domain. Mutation of Tyr-267 completely abrogated and
      mutation of Tyr-363 reduced Ack1-induced AR reporter activation and recruitment
      of AR to the androgen-responsive enhancer. Expression of AR point mutants
      inhibited Ack1-driven xenograft tumor growth. Thus, Ack1 activated by surface
      signals or oncogenic mechanisms may directly enhance AR transcriptional function
      and promote androgen-independent progression of prostate cancer. Targeting the
      Ack1 kinase may be a potential therapeutic strategy in prostate cancer.

PMID- 17494761
TI  - Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins.
AB  - Transcription factors and other allosteric cell signaling proteins contain a
      disproportionate number of domains or segments that are intrinsically disordered
      (ID) under native conditions. In many cases folding of these segments is coupled
      to binding with one or more of their interaction partners, suggesting that
      intrinsic disorder plays an important functional role. Despite numerous
      hypotheses for the role of ID domains in regulation, a mechanistic model has yet
      to be established that can quantitatively assess the importance of intrinsic
      disorder for intramolecular site-to-site communication, the hallmark property of
      allosteric proteins. Here, we present such a model and show that site-to-site
      allosteric coupling is maximized when intrinsic disorder is present in the
      domains or segments containing one or both of the coupled binding sites. This
      result not only explains the prevalence of ID domains in regulatory proteins, it
      also calls into question the classical mechanical view of energy propagation in
      proteins, which predicts that site-to-site coupling would be maximized when a
      well defined pathway of folded structure connects the two sites. Furthermore, in
      showing that the coupling mechanism conferred by intrinsic disorder is robust and
      independent of the network of interactions that physically link the coupled
      sites, unique insights are gained into the energetic ground rules that govern
      site-to-site communication in all proteins.

PMID- 17494762
TI  - Symbiosis as an adaptive process and source of phenotypic complexity.
AB  - Genomics has revealed that inheritance systems of separate species are often not
      well segregated: genes and capabilities that evolve in one lineage are often
      stably acquired by another lineage. Although direct gene transfer between species
      has occurred at some level in all major groups, it appears to be far more
      frequent in prokaryotes than in multicellular eukaryotes. An alternative to
      incorporating novel genes into a recipient genome is acquiring a stable, possibly
      heritable, symbiotic association and thus enjoying benefits of complementary
      metabolic capabilities. These kinds of symbioses have arisen frequently in
      animals; for example, many insect groups have diversified on the basis of
      symbiotic associations acquired early in their evolutionary histories. The
      resulting associations are highly complex, often involving specialized cell types
      and organs, developmental mechanisms that ensure transfer of symbionts between
      generations, and mechanisms for controlling symbiont proliferation and location.
      The genomes of long-term obligate symbionts often undergo irreversible gene loss
      and deterioration even as hosts evolve dependence on them. In some cases, animal
      genomes may have acquired genes from symbionts, mirroring the gene uptake from
      mitochondrial and plastid genomes. Multiple symbionts often coexist in the same
      host, resulting in coadaptation among several phylogenetically distant genomes.

PMID- 17494763
TI  - ApoER2/VLDL receptor and Dab1 in the rostral migratory stream function in
      postnatal neuronal migration independently of Reelin.
AB  - Postnatal migration of interneuron precursors from the subventricular zone to the
      olfactory bulb occurs in chains that form the substrate for the rostral migratory
      stream. Reelin is suggested to induce detachment of neuroblasts from the chains
      when they arrive at the olfactory bulb. Here we show that ApoER2 and possibly
      very-low-density lipoprotein receptor (VLDLR) and their intracellular adapter
      protein Dab1 are involved in chain formation most likely independent of Reelin. F
      spondin, which is present in the stream, may act as ligand for ApoER2 and VLDLR.
      In mice lacking either both receptors or Dab1 chain formation is severely
      compromised, and as a consequence the rostral migratory stream is virtually
      absent and neuroblasts accumulate in the subventricular zone. The mutant animals
      exhibit severe neuroanatomical defects in the subventricular zone and in the
      olfactory bulb. These data demonstrate a cell-autonomous function of ApoER2, and
      most likely VLDLR and Dab1, in postnatal migration of neuroblasts in the
      forebrain, which is suggested to depend on ligands other than Reelin.

PMID- 17494764
TI  - Single-molecule mass spectrometry in solution using a solitary nanopore.
AB  - We introduce a two-dimensional method for mass spectrometry in solution that is
      based on the interaction between a nanometer-scale pore and analytes. As an
      example, poly(ethylene glycol) molecules that enter a single alpha-hemolysin pore
      cause distinct mass-dependent conductance states with characteristic mean
      residence times. The conductance-based mass spectrum clearly resolves the repeat
      unit of ethylene glycol, and the mean residence time increases monotonically with
      the poly(ethylene glycol) mass. This technique could prove useful for the real
      time characterization of molecules in solution.

PMID- 17494765
TI  - Integrated network analysis identifies nitric oxide response networks and
      dihydroxyacid dehydratase as a crucial target in Escherichia coli.
AB  - Nitric oxide (NO) is used by mammalian immune systems to counter microbial
      invasions and is produced by bacteria during denitrification. As a defense,
      microorganisms possess a complex network to cope with NO. Here we report a
      combined transcriptomic, chemical, and phenotypic approach to identify direct NO
      targets and construct the biochemical response network. In particular, network
      component analysis was used to identify transcription factors that are perturbed
      by NO. Such information was screened with potential NO reaction mechanisms and
      phenotypic data from genetic knockouts to identify active chemistry and direct NO
      targets in Escherichia coli. This approach identified the comprehensive E. coli
      NO response network and evinced that NO halts bacterial growth via inhibition of
      the branched-chain amino acid biosynthesis enzyme dihydroxyacid dehydratase.
      Because mammals do not synthesize branched-chain amino acids, inhibition of
      dihydroxyacid dehydratase may have served to foster the role of NO in the immune
      arsenal.

PMID- 17494766
TI  - Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule
      antagonists.
AB  - The developmentally important Hedgehog (Hh) signaling pathway has recently been
      implicated in several forms of solid cancer. Current drug development programs
      focus on targeting the protooncogene Smoothened, a key transmembrane pathway
      member. These drug candidates, albeit promising, do not address the scenario in
      which pathway activation occurs downstream of Smoothened, as observed in cases of
      medulloblastoma, glioma, pericytoma, breast cancer, and prostate cancer. A
      cellular screen for small-molecule antagonists of GLI-mediated transcription,
      which constitutes the final step in the Hh pathway, revealed two molecules that
      are able to selectively inhibit GLI-mediated gene transactivation. We provide
      genetic evidence of downstream pathway blockade by these compounds and
      demonstrate the ineffectiveness of upstream antagonists such as cyclopamine in
      such situations. Mechanistically, both inhibitors act in the nucleus to block GLI
      function, and one of them interferes with GLI1 DNA binding in living cells.
      Importantly, the discovered compounds efficiently inhibited in vitro tumor cell
      proliferation in a GLI-dependent manner and successfully blocked cell growth in
      an in vivo xenograft model using human prostate cancer cells harboring downstream
      activation of the Hh pathway.

PMID- 17494767
TI  - Extreme accumulation of nucleotides in simulated hydrothermal pore systems.
AB  - We simulate molecular transport in elongated hydrothermal pore systems influenced
      by a thermal gradient. We find extreme accumulation of molecules in a wide
      variety of plugged pores. The mechanism is able to provide highly concentrated
      single nucleotides, suitable for operations of an RNA world at the origin of
      life. It is driven solely by the thermal gradient across a pore. On the one hand,
      the fluid is shuttled by thermal convection along the pore, whereas on the other
      hand, the molecules drift across the pore, driven by thermodiffusion. As a
      result, millimeter-sized pores accumulate even single nucleotides more than 10(8)
      fold into micrometer-sized regions. The enhanced concentration of molecules is
      found in the bulk water near the closed bottom end of the pore. Because the
      accumulation depends exponentially on the pore length and temperature difference,
      it is considerably robust with respect to changes in the cleft geometry and the
      molecular dimensions. Whereas thin pores can concentrate only long
      polynucleotides, thicker pores accumulate short and long polynucleotides equally
      well and allow various molecular compositions. This setting also provides a
      temperature oscillation, shown previously to exponentially replicate DNA in the
      protein-assisted PCR. Our results indicate that, for life to evolve, complicated
      active membrane transport is not required for the initial steps. We find that
      interlinked mineral pores in a thermal gradient provide a compelling high
      concentration starting point for the molecular evolution of life.

PMID- 17494768
TI  - A secretory pathway-localized cation diffusion facilitator confers plant
      manganese tolerance.
AB  - Manganese toxicity is a major problem for plant growth in acidic soils, but
      cellular mechanisms that facilitate growth in such conditions have not been
      clearly delineated. Established mechanisms that counter metal toxicity in plants
      involve chelation and cytoplasmic export of the metal across the plasma or
      vacuolar membranes out of the cell or sequestered into a large organelle,
      respectively. We report here that expression of the Arabidopsis and poplar MTP11
      cation diffusion facilitators in a manganese-hypersensitive yeast mutant restores
      manganese tolerance to wild-type levels. Microsomes from yeast expressing AtMTP11
      exhibit enhanced manganese uptake. In accord with a presumed function of MTP11 in
      manganese tolerance, Arabidopsis mtp11 mutants are hypersensitive to elevated
      levels of manganese, whereas plants overexpressing MTP11 are hypertolerant. In
      contrast, sensitivity to manganese deficiency is slightly decreased in mutants
      and increased in overexpressing lines. Promoter-GUS studies showed that AtMTP11
      is most highly expressed in root tips, shoot margins, and hydathodes, but not in
      epidermal cells and trichomes, which are generally associated with manganese
      accumulation. Surprisingly, imaging of MTP11-EYFP fusions demonstrated that MTP11
      localizes neither to the plasma membrane nor to the vacuole, but to a punctate
      endomembrane compartment that largely coincides with the distribution of the
      trans-Golgi marker sialyl transferase. Golgi-based manganese accumulation might
      therefore result in manganese tolerance through vesicular trafficking and
      exocytosis. In accord with this proposal, Arabidopsis mtp11 mutants exhibit
      enhanced manganese concentrations in shoots and roots. We propose that Golgi
      mediated exocytosis comprises a conserved mechanism for heavy metal tolerance in
      plants.

PMID- 17494769
TI  - Directed evolution of gene-shuffled IFN-alpha molecules with activity profiles
      tailored for treatment of chronic viral diseases.
AB  - Type I IFNs are unusually pleiotropic cytokines that bind to a single
      heterodimeric receptor and have potent antiviral, antiproliferative, and immune
      modulatory activities. The diverse effects of the type I IFNs are of differential
      therapeutic importance; in cancer therapy, an enhanced antiproliferative effect
      may be beneficial, whereas in the therapy of viral infections (such as hepatitis
      B and hepatitis C), the antiproliferative effects lead to dose limiting bone
      marrow suppression. Studies have shown that various members of the natural IFN
      alpha family and engineered variants, such as IFN-con1, vary in the ratios
      between various IFN-mediated cellular activities. We used DNA shuffling to
      explore and confirm the hypothesis that one could simultaneously increase the
      antiviral and Th1-inducing activity and decrease the antiproliferative activity.
      We report IFN-alpha hybrids wherein the ratio of antiviral:antiproliferative and
      Th1-inducing: antiproliferative potencies are markedly increased with respsect to
      IFN-con1 (75- and 80-fold, respectively). A four-residue motif that overlaps with
      the IFNAR1 binding site and is derived by cross breeding with a pseudogene
      contributes significantly to this phenotype. These IFN-alphas have an activity
      profile that may result in an improved therapeutic index and, consequently,
      better clinical efficacy for the treatment of chronic viral diseases such as
      hepatitis B virus, human papilloma virus, HIV, or chronic hepatitis C.

PMID- 17494770
TI  - Independent sorting-out of thousands of duplicated gene pairs in two yeast
      species descended from a whole-genome duplication.
AB  - Among yeasts that underwent whole-genome duplication (WGD), Kluyveromyces
      polysporus represents the lineage most distant from Saccharomyces cerevisiae. By
      sequencing the K. polysporus genome and comparing it with the S. cerevisiae
      genome using a likelihood model of gene loss, we show that these species diverged
      very soon after the WGD, when their common ancestor contained >9,000 genes. The
      two genomes subsequently converged onto similar current sizes (5,600 protein
      coding genes each) and independently retained sets of duplicated genes that are
      strikingly similar. Almost half of their surviving single-copy genes are not
      orthologs but paralogs formed by WGD, as would be expected if most gene pairs
      were resolved independently. In addition, by comparing the pattern of gene loss
      among K. polysporus, S. cerevisiae, and three other yeasts that diverged after
      the WGD, we show that the patterns of gene loss changed over time. Initially,
      both members of a duplicate pair were equally likely to be lost, but loss of the
      same gene copy in independent lineages was increasingly favored at later time
      points. This trend parallels an increasing restriction of reciprocal gene loss to
      more slowly evolving gene pairs over time and suggests that, as duplicate genes
      diverged, one gene copy became favored over the other. The apparent low initial
      sequence divergence of the gene pairs leads us to propose that the yeast WGD was
      probably an autopolyploidization.

PMID- 17494771
TI  - Achieving high-density states through shock-wave loading of precompressed
      samples.
AB  - Materials can be experimentally characterized to terapascal pressures by sending
      a laser-induced shock wave through a sample that is precompressed inside a
      diamond-anvil cell. This combination of static and dynamic compression methods
      has been experimentally demonstrated and ultimately provides access to the 10- to
      100-TPa (0.1-1 Gbar) pressure range that is relevant to planetary science,
      testing first-principles theories of condensed matter, and experimentally
      studying a new regime of chemical bonding.

PMID- 17494773
TI  - MSVM-RFE: extensions of SVM-RFE for multiclass gene selection on DNA microarray
      data.
AB  - MOTIVATION: Given the thousands of genes and the small number of samples, gene
      selection has emerged as an important research problem in microarray data
      analysis. Support Vector Machine-Recursive Feature Elimination (SVM-RFE) is one
      of a group of recently described algorithms which represent the stat-of-the-art
      for gene selection. Just like SVM itself, SVM-RFE was originally designed to
      solve binary gene selection problems. Several groups have extended SVM-RFE to
      solve multiclass problems using one-versus-all techniques. However, the genes
      selected from one binary gene selection problem may reduce the classification
      performance in other binary problems. RESULTS: In the present study, we propose a
      family of four extensions to SVM-RFE (called MSVM-RFE) to solve the multiclass
      gene selection problem, based on different frameworks of multiclass SVMs. By
      simultaneously considering all classes during the gene selection stages, our
      proposed extensions identify genes leading to more accurate classification.

PMID- 17494772
TI  - From rhomboid function to structure and back again.

PMID- 17494774
TI  - Managing the nervous system effects of sepsis.

PMID- 17494775
TI  - Statins and lung cancer risk.

PMID- 17494776
TI  - Another nail in albumin's coffin.

PMID- 17494777
TI  - Maintaining therapeutic anticoagulation: the importance of keeping "within
      range".

PMID- 17494778
TI  - Is brachial artery peak velocity variation ready for prime time?

PMID- 17494779
TI  - Statins reduce the risk of lung cancer in humans: a large case-control study of
      US veterans.
AB  - BACKGROUND: Statins are commonly used cholesterol-lowering agents that are noted
      to suppress tumor cell growth in several in vitro and animal models. METHODS: We
      studied the association of lung cancer and the use of statins in patients
      enrolled in the Veterans Affairs (VA) Health Care System. A retrospective case
      control study nested in a cohort study was conducted using prospectively
      collected data from the Veterans Integrated Service Networks 16 VA database from
      1998 to 2004. We analyzed data on 483,733 patients from eight states located in
      south central United States. The primary variables of interest were lung cancer
      and the use of statins prior to the diagnosis of lung cancer. Multiple logistic
      regression analysis was done to adjust for covariates including age, sex, body
      mass index, smoking, diabetes, and race. Statistical software was used for
      statistical computing. RESULTS: Of the 483,733 patients in the study, 163,662
      patients (33.8%) were receiving statins and 7,280 patients (1.5%) had a primary
      diagnosis of lung cancer. Statin use > 6 months was associated with a risk
      reduction of lung cancer of 55% (adjusted odds ratio, 0.45; 95% confidence
      interval, 0.42 to 0.48; p < 0.01). Furthermore, the protective effect of statin
      was seen across different age and racial groups and was irrespective of the
      presence of diabetes, smoking, or alcohol use. CONCLUSIONS: Statins appear to be
      protective against the development of lung cancer, and further studies need to be
      done to define the clinical utility of statins as chemo protective agents.

PMID- 17494780
TI  - Effects of hypercapnia on BP in hypoalbuminemic and Nagase analbuminemic rats.
AB  - STUDY OBJECTIVE: To determine if animals with abnormally low albumin levels are
      more susceptible to the effects of hypercapnia on BP compared to normal animals.
      DESIGN: Prospective, controlled laboratory experiment. SETTING: University
      research laboratory. ANIMALS: Eighteen male Sprague-Dawley rats: 6 rats 10 to 12
      weeks old (young Sprague-Dawley [YSD]), 6 rats 6 to 9 months old (old Sprague
      Dawley [OSD]), and 6 rats 10 to 12 weeks old (Nagase analbuminemic mutant Sprague
      Dawley [NAR]). METHODS: Under general anesthesia and paralysis, we varied the
      Paco(2) by changing the respiratory rate on mechanical ventilation. Mean arterial
      pressure (MAP) was monitored in a continuous fashion. We obtained arterial blood
      for blood gas and electrolyte analysis, and nitric oxide (NO) production.
      RESULTS: OSD rats had reduced serum albumin, while NAR rats were analbuminemic.
      Although NAR animals had a decreased buffer capacity compared to age-matched
      control animals (0.010 vs 0.013, p < 0.05), the MAP decreased in an identical
      fashion in all three groups. NO production increased with hypercapnia but was
      similar in all three groups. However, NAR rats had consistently higher plasma
      strong ion gap (2.8 to 4.1 mEq/L greater) compared to either YSD or OSD rats (p <
      0.01), and baseline strong ion difference (mean +/- SD) was significantly lower
      in NAR rats (28.7 +/- 2.1 mEq/L) compared to either YSD rats (33.0 +/- 5.1 mEq/L)
      or OSD rats (31.2 +/- 5.1 mEq/L) [p < 0.05]. CONCLUSIONS: These findings suggest
      that analbuminemic or hypoalbuminemic rats are not more susceptible to
      hypercapnia-induced hemodynamic instability. Baseline values for apparent strong
      ion difference are lower in NA rats consistent with a reduced buffer base
      resulting from analbuminemia.

PMID- 17494781
TI  - Radial artery pulse pressure variation correlates with brachial artery peak
      velocity variation in ventilated subjects when measured by internal medicine
      residents using hand-carried ultrasound devices.
AB  - BACKGROUND: Rapid prediction of the effect of volume expansion is crucial in
      unstable patients receiving mechanical ventilation. Both radial artery pulse
      pressure variation (DeltaPP) and change of aortic blood flow peak velocity are
      accurate predictors but may be impractical point-of-care tools. PURPOSES: We
      sought to determine whether respiratory changes in the brachial artery blood flow
      velocity (DeltaVpeak-BA) as measured by internal medicine residents using a hand
      carried ultrasound (HCU) device could provide an accurate corollary to DeltaPP in
      patients receiving mechanical ventilation. METHODS: Thirty patients passively
      receiving volume-control ventilation with preexisting radial artery catheters
      were enrolled. The brachial artery Doppler signal was recorded and analyzed by
      blinded internal medicine residents using a HCU device. Simultaneous radial
      artery pulse wave and central venous pressure recordings (when available) were
      analyzed by a blinded critical care physician. RESULTS: A Doppler signal was
      obtained in all 30 subjects. The DeltaVpeak-BA correlated well with DeltaPP (r =
      0.84) with excellent agreement (weighted kappa, 0.82) and limited intraobserver
      variability (2.8 +/- 2.8%) [mean +/- SD]. A DeltaVpeak-BA cutoff of 16% was
      highly predictive of DeltaPP > or = 13% (sensitivity, 91%; specificity, 95%). A
      poor correlation existed between the CVP and both DeltaVpeak-BA (r = - 0.21) and
      DeltaPP (r = - 0.16). CONCLUSIONS: The HCU Doppler assessment of the DeltaVpeak
      BA as performed by internal medicine residents is a rapid, noninvasive bedside
      correlate to DeltaPP, and a DeltaVpeak-BA cutoff of 16% may prove useful as a
      point-of-care tool for the prediction of volume responsiveness in patients
      receiving mechanical ventilation.

PMID- 17494782
TI  - The early phase of the minute ventilation recovery curve predicts extubation
      failure better than the minute ventilation recovery time.
AB  - STUDY OBJECTIVES: To determine, in patients who had successful outcomes in
      spontaneous breathing trials (SBTs), whether the analysis of the minute
      ventilation (Ve) recovery time obtained by minute-by-minute sequential monitoring
      after placing the patient back on mechanical ventilation (MV) may be useful in
      predicting extubation outcome. DESIGN: Twelve-month prospective observational
      study. SETTING: Medical-surgical ICU of a university hospital. PATIENTS: Ninety
      three patients receiving > 48 h of MV. INTERVENTIONS: Baseline respiratory
      parameters (ie, respiratory rate, tidal volume, and Ve) were measured under
      pressure support ventilation prior to the SBT. After tolerating the SBT, patients
      again received MV with their pre-SBT ventilator settings, and respiratory
      parameters were recorded minute by minute. MEASUREMENTS AND RESULTS: Seventy-four
      patients (80%) were successfully extubated, and 19 patients (20%) were
      reintubated. Reintubated patients were similar to non-reintubated patients in
      baseline respiratory parameters and baseline variables, except for age and COPD
      diagnosis. The recovery time needed to reduce Ve to half the difference between
      the Ve measured at the end of a successful SBT and basal Ve (RT50%DeltaVe) was
      lower in patients who had undergone successful extubation than in those who had
      failed extubation (mean [+/- SD] time, 2.7 +/- 1.2 vs 10.8 +/- 8.4 min,
      respectively; p < 0.001). Multiple logistic regression adjusted for age, sex,
      comorbid status, diagnosis (ie, neurocritical vs other), and severity of illness
      revealed that neurocritical disease (odds ratio [OR], 7.6; p < 0.02) and
      RT50%DeltaVe (OR, 1.7; p < 0.01) were independent predictors of extubation
      outcome. The area under the receiver operating characteristic curve for the
      predictive model was 0.89 (95% confidence interval, 0.81 to 0.96). CONCLUSION:
      Determination of the RT50%DeltaVe at the bedside may be a useful adjunct in the
      decision to extubate, with better results found in nonneurocritical patients.

PMID- 17494783
TI  - Area of residence, birthplace, and asthma in Puerto Rican children.
AB  - RATIONALE: Puerto Ricans have the highest prevalence of asthma among all ethnic
      groups in the United States. There have been no studies that directly compare the
      burden of asthma between Puerto Ricans living in Puerto Rico and those living in
      the mainland United States. OBJECTIVE: To examine the relation between
      birthplace, area of residence, and asthma in Puerto Rican children. METHODS:
      Multistage population-based probability sample of children in the San Juan and
      Caguas metropolitan areas in Puerto Rico and in the Bronx, NY. Information was
      collected in a household survey of 2,491 children and their primary caretakers.
      RESULTS: The overall prevalence of asthma among Puerto Rican children in this
      study was very high (38.6%). Although children from Puerto Rico had higher
      socioeconomic status and lower rates of premature birth and prenatal smoke
      exposure, the prevalence of lifetime asthma was higher in Puerto Rican children
      living in Puerto Rico than in Puerto Rican children living in the South Bronx
      (41.3% vs 35.3%, p = 0.01). In multivariable analysis, residence in Puerto Rico
      was associated with increased odds of lifetime asthma (odds ratio [OR], 1.27; 95%
      confidence interval [CI], 1.03 to 1.57) and lifetime hospitalization for asthma
      (OR, 1.47; 95% CI, 1.04-2.07). CONCLUSIONS: Puerto Rican children in Puerto Rico
      had a higher risk of asthma than Puerto Rican children in the South Bronx,
      highlighting the need for further examination of the roles of migration,
      acculturation, and environmental and psychosocial factors on the development of
      asthma in this high-risk population.

PMID- 17494784
TI  - Safety of sputum induction with hypertonic saline solution in exercise-induced
      bronchoconstriction.
AB  - BACKGROUND: The safety of sputum induction (SI) is well described in stable
      asthma, but the safety of SI in exercise-induced bronchoconstriction (EIB) has
      not been established. OBJECTIVES: Our goals were to examine the relationship
      between the severity of EIB and bronchoconstriction during SI, and to determine
      if SI conducted after exercise challenge increases the risk of excess
      bronchoconstriction during SI. METHODS: SI was conducted in 32 patients with mild
      to-moderate asthma (baseline FEV(1), 86 +/- 9% of predicted [mean +/- SD]) with
      EIB (15 to 63% reduction in FEV(1) following exercise challenge) following
      pretreatment with albuterol using 3% saline solution and repeated on a separate
      day 30-min after exercise challenge. RESULTS: There was a reduction in peak
      expiratory flow rate (PEFR) during SI without exercise (mean maximum reduction vs
      baseline, 4.0% at 10 min; 95% confidence interval [CI], 1.0 to 7.1; p = 0.02) and
      during SI 30 min following exercise (mean maximum reduction vs baseline, 5.2% at
      8 min; 95% CI, 1.0 to 7.5; p < or = 0.01); however, there was no difference
      between the PEFR reductions during SI without or following exercise challenge.
      The best predictor of reduction in PEFR during SI was the preprocedure FEV(1),
      while the severity of EIB was not associated with bronchoconstriction during SI.
      CONCLUSIONS: We conclude that SI can be performed safely following exercise
      challenge in asthmatics with EIB, and that the severity of EIB prior to SI is not
      a major determinant of bronchoconstriction during SI.

PMID- 17494785
TI  - Differential flow analysis of exhaled nitric oxide in patients with asthma of
      differing severity.
AB  - BACKGROUND: The majority of asthmatic patients achieve control of their illness;
      others do not. It is therefore crucial to validate/develop strategies that help
      the clinician monitor the disease, improving the response to treatment. METHODS:
      We have quantified the inflammation in central and peripheral airways by
      measuring exhaled nitric oxide (NO) at multiple exhalation flows in 56 asthmatics
      at different levels of severity (mild, n = 10; moderate stable, n = 17; moderate
      during exacerbation, n = 11; severe, n = 18, 7 of whom were receiving oral
      corticosteroids) and 18 healthy control subjects. The reproducibility of the
      measurement was also assessed. RESULTS: Bronchial NO (Jno) in patients with mild
      asthma (2,363 +/- 330 pL/s) [mean +/- SD] was higher than in patients with
      moderate stable asthma (1,300 +/- 59 pL/s, p < 0.0005), in patients with severe
      asthma receiving inhaled corticosteroids (ICS) [1,015 +/- 67 pL/s, p < 0.0005],
      and healthy control subjects (721 +/- 22 pL/s, p < 0.0001). There were no
      differences between Jno in patients with mild asthma compared to patients with
      severe asthma receiving ICS and oral corticosteroids (2,225 +/- 246 pL/s).
      Patients with exacerbations showed a higher Jno (3,475 +/- 368.9 pL/s, p < 0.05)
      compared to the other groups. Alveolar NO was higher in patients with severe
      asthma receiving oral corticosteroids (3.0 +/- 0.1 parts per billion [ppb], p <
      0.0001) than in the other groups but was not significantly higher than in
      patients with moderate asthma during exacerbation (2.8 +/- 0.3 ppb). No
      differences were seen in NO diffusion levels between the different asthma groups.
      All the measurements were highly reproducible and free of day-to-day and diurnal
      variations. CONCLUSIONS: Differential flow analysis of exhaled NO provides
      additional information about the site of inflammation in asthma and may be useful
      in assessing the response of peripheral inflammation to therapy.

PMID- 17494786
TI  - Measurements of desmosine and isodesmosine by mass spectrometry in COPD.
AB  - OBJECTIVES: Application of mass spectrometry (MS) for direct measurements of
      desmosine (D) and isodesmosine (I) in urine, plasma, and sputum as markers of
      elastin degradation in patients with alpha(1)-antitrypsin deficiency (AATD) and
      non-AATD-related COPD. BACKGROUND: In COPD patients, the lungs undergo elastin
      injury, which can be monitored by measurements of D and I in body fluids as
      specific markers of elastin degradation using the specificity and sensitivity of
      MS. METHODS: Acid hydrolysis of blood plasma, 24-h urine and sputum measurements,
      followed by chromatographic separation for mass spectrometric analysis. RESULTS:
      Each patient group had levels of plasma D and I that were statistically
      significantly higher than those of control subjects. AATD patients had higher
      levels than COPD patients with normal alpha(1)-antitrypsin (AAT) levels. Twenty
      four-hour urine measurements demonstrated no significant difference in total
      levels of D and I among control subjects and patients but showed a free (unbound)
      concentration of D and I in urine, which was statistically significantly higher
      in patients with COPD with and without AAT. The D and I levels in the sputum of
      patients with AATD exceeded the levels in COPD patients with normal AAT levels.
      CONCLUSIONS: MS allows a sensitive and specific analysis of D and I in body
      fluids. The quantification of D and I in sputum, along with increases of D and I
      in plasma and an elevated free component of D and I in urine provide indexes that
      characterize patients with COPD and can be followed in relation to the course of
      the disease and/or therapy.

PMID- 17494787
TI  - Obstructive sleep apnea, hypertension, and their interaction on arterial
      stiffness and heart remodeling.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and hypertension are
      independently associated with increased stiffness of large arteries that may
      contribute to left ventricular (LV) remodeling. We sought to investigate the
      impact of OSA, hypertension, and their association with arterial stiffness and
      heart structure. DESIGN: We studied 60 middle-aged subjects classified into four
      groups according to the absence or presence of severe OSA with and without
      hypertension. All participants were free of other comorbidities. The groups were
      matched for age, sex, and body mass index. MEASUREMENTS AND RESULTS: Full
      polysomnography, pulse-wave velocity (PWV), and transthoracic echocardiography
      were performed in all participants. Compared with normotensive subjects without
      OSA, PWV, left atrial diameter, interventricular septal thickness, LV posterior
      wall thickness, LV mass index, and percentage of LV hypertrophy had similar
      increases in normotensive OSA and patients with hypertension and no OSA (p < 0.05
      for all comparisons), with a significant further increase in PWV, LV mass index,
      and percentage of LV hypertrophy in subjects with OSA and hypertension.
      Multivariate regression analysis showed that PWV was associated with systolic BP
      (p < 0.001) and apnea-hypopnea index (p = 0.002). The only independent variable
      associated with LV mass index was PWV (p < 0.0001). CONCLUSIONS: Severe OSA and
      hypertension are associated with arterial stiffness and heart structure
      abnormalities of similar magnitude, with additive effects when both conditions
      coexist. Increased large arterial stiffness contributes to ventricular afterload
      and may help to explain heart remodeling in both OSA and hypertension.

PMID- 17494788
TI  - Obstructive sleep apnea syndrome is associated with some components of metabolic
      syndrome.
AB  - BACKGROUND: Obesity, hypertension, dyslipidemia, and hyperglycemia are prevalent
      in obstructive sleep apnea syndrome (OSAS). Metabolic syndrome, however, is
      defined by visceral fat obesity plus at least two of these factors. However,
      whether OSAS contributes to the development of metabolic syndrome has not been
      defined. We investigated whether the components of metabolic syndrome were
      associated with OSAS in nonobese patients. METHODS: We investigated the
      occurrence of hypertension, dyslipidemia, and hyperglycemia in 42 men with OSAS
      and 52 men without OSAS matched for age, body mass index (BMI), and visceral fat
      accumulation. RESULTS: Although serum levels of triglycerides, high-density
      lipoprotein cholesterol, and diastolic BP did not differ significantly between
      the two groups, fasting blood glucose (111 +/- 6 mg/dL vs 93 +/- 3 mg/dL) [mean
      +/- SE] and the percentage of hypertensive patients (45% vs 15%) were
      significantly higher in the group with OSAS. In addition, a significantly higher
      percentage of patients with OSAS (19% vs 4%) had at least two of the following:
      hypertension, hyperglycemia, and dyslipidemia. Logistic regression analysis
      showed that the apnea-hypopnea index value was the predictor of number of
      metabolic syndrome parameters such as hypertension, hyperglycemia, and
      dyslipidemia, while BMI and lowest arterial oxygen saturation during sleep did
      not. CONCLUSION: Independent of visceral fat obesity, OSAS was associated with
      hypertension, dyslipidemia, and hyperglycemia. It is possible that OSAS may
      predispose even nonobese patients to the development of metabolic syndrome.

PMID- 17494789
TI  - Fixed and autoadjusting continuous positive airway pressure treatments are not
      similar in reducing cardiovascular risk factors in patients with obstructive
      sleep apnea.
AB  - BACKGROUND: A strong association between obstructive sleep apnea (OSA) and the
      risk for cardiovascular and cerebrovascular diseases has been reported.
      Continuous positive airway pressure (CPAP) is the first-line therapy for OSA,
      able not only to reduce daytime sleepiness but also to improve cardiovascular and
      metabolic outcomes. Autoadjusting CPAP (APAP), an alternative treatment to CPAP,
      can reduce OSA symptoms while increasing long-term CPAP compliance without the
      high costs of CPAP titration. However, no data are available on the effects of
      APAP on cardiovascular risk factors METHODS: We performed standard full
      polysomnography; obtained plasma levels of glucose, insulin, and C-reactive
      protein (CRP); and measured systolic BP (SBP) and diastolic BP (DBP) in 31
      patients with newly diagnosed, severe OSA. After standard CPAP titration, all
      subjects were randomized to CPAP or APAP treatment. Measurements were obtained at
      baseline and after 3 months of treatment. RESULTS: The two groups were similar in
      terms of age, sex, body mass index (BMI), and severity of OSA. SBP, DBP, heart
      rate (HR), homeostasis model assessment index (HOMA-IR), and CRP were similar in
      the two groups. After 3 months of treatment, BMI, HR, and compliance to therapy
      were also comparable. OSA indexes were significantly reduced in both groups.
      Significant reductions in SBP, DBP, and HOMA-IR were observed in the CPAP group
      but not in the APAP group, while CRP plasma levels were similarly reduced.
      CONCLUSIONS: Our results suggest that CPAP and APAP, despite significant effects
      on OSA indexes and symptoms, do not improve cardiovascular risk factors in the
      same fashion.

PMID- 17494790
TI  - Relationship between serum substance P levels and daytime sleepiness in
      obstructive sleep apnea syndrome.
AB  - OBJECTIVE: We hypothesized that intermittent hypoxia might influence serum
      substance P levels, and that this effect might in turn contribute in excessive
      daytime sleepiness (EDS) in patients with obstructive sleep apnea syndrome
      (OSAS). PATIENTS AND METHODS: Fifty-five patients with newly diagnosed OSAS and
      15 age-matched nonapneic control subjects were enrolled in this study. Full
      polysomnography was performed in all patients. Single blood samples were drawn
      between 8:00 am and 9:00 am after the sleep study. Substance P levels were
      analyzed with a competitive enzyme immunoassay (substance P EIA kit; Cayman
      Chemical; Ann Arbor, MI). RESULTS: There were no significant differences in age,
      gender, body mass index, smoking habit, and snoring between the two groups. Serum
      substance P levels in the OSAS group were significantly lower than that in the
      control group (p < 0.0001). Serum substance P levels were positively correlated
      with rapid eye movement sleep (r = 0.330, p = 0.049) and slow-wave sleep (r =
      0.324, p = 0.049) phases. Serum substance P levels were negatively correlated
      with Epworth sleepiness scale score (r = - 0.253, p = 0.048), number of total
      apneas during the night (r = - 0.247, p = 0.036), number of respiratory events
      during the night (r = - 0.266, p = 0.024), apnea-hypopnea index (r = - 0.287, p =
      0.015), respiratory arousal index (r = - 0.267, p = 0.026), time spent in apnea
      and hypopnea (r = - 0.307, p = 0.01), average oxygen desaturation (r = - 0.265, p
      = 0.026), and oxygen desaturation index (r = - 0.254, p = 0.031). CONCLUSION: We
      concluded that EDS seen in some of the OSAS patients might be associated with
      various pathophysiologic mechanisms including substance P levels.

PMID- 17494791
TI  - Sympathetic chemoreflex responses in obstructive sleep apnea and effects of
      continuous positive airway pressure therapy.
AB  - BACKGROUND: Sympathetic nerve activity is increased in awake and regularly
      breathing patients with obstructive sleep apnea (OSA). Over time, repetitive
      hypoxic stress could alter sympathetic chemoreflex function in OSA. METHODS: We
      determined the responses to acute hypoxia (fraction of inspired oxygen of 0.1,
      for 5 min), static handgrip exercise, and the cold pressor test (CPT) in 24
      patients with OSA (age, 50 +/- 3 years [mean +/- SEM]; apnea-hypopnea index, 47
      +/- 6 events per hour) and in 14 age- and weight-matched nonapneic control
      subjects. Muscle sympathetic nerve activity (MSNA) [peroneal microneurography],
      BP, and ventilation were monitored. RESULTS: Basal MSNA was higher in OSA
      patients compared to control subjects (45 +/- 4 bursts per minute vs 33 +/- 4
      bursts per minute, respectively; p < 0.05). Furthermore, compared to control
      subjects, the MSNA responses to hypoxia were markedly enhanced in OSA (p <
      0.001). Whereas the ventilatory responses to hypoxia tended to be increased in
      OSA (p = 0.06), the BP responses did not differ between the groups (p = 0.45).
      The neurocirculatory reflex responses to handgrip exercise and to the CPT were
      similar in the two groups (p = not significant). In OSA patients who were
      retested after 1 to 24 months of continuous positive airway pressure (CPAP)
      therapy (n = 11), basal MSNA (p < 0.01) and the responses of MSNA to hypoxia (p <
      0.01) decreased significantly, whereas the ventilatory responses remained
      unchanged (p = 0.82). CONCLUSION: These data suggest that the sympathetic
      responses to hypoxic chemoreflex stimulation are enhanced in OSA and may
      normalize in part following CPAP therapy.

PMID- 17494792
TI  - Cost-effectiveness of interferon-gamma release assay screening for latent
      tuberculosis infection treatment in Germany.
AB  - OBJECTIVES: To assess the cost-effectiveness of the new QuantiFERON-TB Gold In
      Tube (QFT-G) [Cellestis; Carnegie, VIC, Australia] assay for screening and
      treating of persons who have had close contact with tuberculosis (TB) patients
      and are suspected of having latent tuberculosis infection (LTBI) [hereafter
      called close-contacts] in Germany. METHODS: The health and economic outcomes of
      isoniazid treatment of 20-year-old close-contacts were compared in a Markov model
      over a period of 20 years, using two different cutoff values for the tuberculin
      skin test (TST), the QFT-G assay alone, or the QFT-G assay as a confirmatory test
      for the TST results. RESULTS: QFT-G assay-based treatment led to cost savings of
      $542.9 and 3.8 life-days gained per LTBI case. TST-based treatment at a 10-mm
      induration size cutoff gained $177.4 and 2.0 life-days gained per test-positive
      contact. When the cutoff induration size for the TST was reduced to 5 mm, the
      incremental cost-effectiveness ratio fell below the willingness-to-pay threshold
      ($30,170 per life-years gained) but resulted in unnecessary treatment of 77% of
      contacts owing to false-positive TST results. Combination with the 5-mm
      induration size TST cutoff value compared to the results of the QFT-G assay alone
      reduced the total costs per 1,000 contacts by 1.8% to $222,869. The number
      treated to prevent 1 TB case was 22 for the two QFT-G assay-based procedures, 40
      for the TST at a cutoff induration size of 10 mm, and 96 for the TST at a cutoff
      induration size of 5 mm. When the sensitivity rates of the TST and the QFT-G
      assay were compounded, the QFT-G assay strategy alone was slightly less costly
      (0.6%) than the two-step approach. CONCLUSIONS: Using the QFT-G assay, but
      especially combining the QFT-G assay following the TST screening of close
      contacts at a cutoff induration size of 5 mm before LTBI treatment is highly cost
      effective in reducing the disease burden of TB.

PMID- 17494793
TI  - Bronchoalveolar cellularity and interleukin-8 levels in measles bronchiolitis
      obliterans.
AB  - BACKGROUND: Measles virus infection may progress to a chronic obstructive process
      including bronchiolitis obliterans (BO). This study investigates pulmonary
      cellular profiles and interleukin (IL)-8 levels in patients with BO following the
      measles. METHODS: BAL fluid was obtained from 12 children with BO who had a
      history of measles pneumonia during an outbreak in 2000 and 2001. BAL cell counts
      and differentials were compared to control patients as well as BAL IL-8 levels,
      which were measured by enzyme-linked immunosorbent assay. Immunohistochemical
      staining of BAL cells and three open-lung biopsy specimens were also analyzed for
      T-cell surface markers CD3, CD4, and CD8. RESULTS: BAL cellular profiles were
      characterized by a significantly increased percentage of neutrophils in the
      measles BO group (median, 16.0%) compared to the control group (2.3%) [p < 0.01].
      BAL IL-8 levels were also markedly increased in the measles BO group (mean +/-
      SD, 418.6 +/- 286.0 pg/mL) compared to the control group (92.8 +/- 126.7 pg/mL)
      [p < 0.01]. BAL IL-8 levels correlated significantly with neutrophil percentages
      in both the measles BO group (r = 0.86, p = 0.000) and the control group (r =
      0.79, p = 0.007). The lymphocyte subsets were characterized by a significantly
      increased number of CD8+ cells, resulting in a decreased CD4/CD8 ratio in the BAL
      and the biopsy specimens. CONCLUSION: These results suggest that pulmonary
      neutrophils and IL-8, along with CD8+ T lymphocytes may play an important role in
      the pathogenesis of BO after measles virus infection.

PMID- 17494794
TI  - Inhalation of Moli1901 in patients with cystic fibrosis.
AB  - BACKGROUND: In cystic fibrosis (CF) patients, the absence or dysfunction of the
      chloride channel CF transmembrane conductance regulator (CFTR) results in reduced
      chloride ion transport in respiratory epithelial cells. Moli1901 stimulates an
      alternative chloride channel and may thus compensate for the CFTR deficiency in
      the airway epithelium of CF patients. METHODS: A phase II, placebo-controlled,
      double-blinded, single-center, multiple (5 consecutive days), rising-dose (daily
      dose, 0.5, 1.5, or 2.5 mg of Moli1901) study was conducted to investigate the
      safety and tolerability of multiple doses of aerosolized inhaled Moli1901 in 24
      patients with CF and stable lung disease. RESULTS: Moli1901 was well tolerated in
      all but one CF patient, in whom a transient significant decrease in FEV(1)
      developed following inhalation, which resolved spontaneously, and in a second
      patient in whom transient throat numbness developed during drug inhalation. A
      significant improvement of FEV(1) was observed in the group receiving treatment
      with 2.5 mg/d Moli1901 compared to the group receiving placebo (p = 0.01
      [Wilcoxon test]). Moli1901 was not detected in the plasma of the highest dose
      group. CONCLUSIONS: The inhalation of Moli1901 up to a total cumulative dose of
      12.5 mg appears to be safe in adult patients with CF. In addition, Moli1901 had a
      sustained beneficial effect on pulmonary function, which supports further studies
      of its efficacy in CF patients.

PMID- 17494795
TI  - Does endothelin play a role in chemoreception during acute hypoxia in normal men?
AB  - BACKGROUND: The peripheral chemoreceptors are the dominant reflex mechanism
      responsible for the rise in ventilation and muscle sympathetic nerve activity
      (MSNA) in response to hypoxia. Animal studies have suggested that endothelin (ET)
      plays an important role in chemosensitivity. Moreover, several human clinical
      conditions in which circulating ET levels are increased are accompanied by
      enhanced chemoreflex sensitivity. Whether ET plays a role in normal human
      chemosensitivity is unknown. METHODS: We determined whether bosentan, a
      nonspecific ET receptor antagonist, would decrease chemoreflex sensitivity in 14
      healthy subjects. We assessed the effects of bosentan on the response to
      isocapnic hypoxia, using a randomized, crossover, double-blinded study design.
      RESULTS: Bosentan increased mean (+/- SEM) plasma ET levels from 1.97 +/- 0.28 to
      2.53 +/- 0.23 pg/mL (p = 0.01). Hypoxia increased mean minute ventilation from
      6.7 +/- 0.3 to 8+/0.4 L/min (p < 0.01), mean MSNA from 100 to 111 +/- 5% (p <
      0.01), mean heart rate from 67 +/- 3 to 86 +/- 3 beats/min (p < 0.01), and mean
      systolic BP from 116 +/- 3 to 122 +/- 3 mm Hg (p < 0.01). However, none of these
      responses differed between therapy with bosentan and therapy with placebo (p =
      0.26). Bosentan did not affect the mean MSNA responses to the apneas, during
      normoxia (change from baseline: placebo, 259 +/- 58%; bosentan, 201 +/- 28%; p =
      0.17) or during hypoxia (change from baseline: placebo, 469 +/- 139%; bosentan,
      329 +/- 46%; p = 0.24). The durations of the voluntary end-expiratory apneas in
      normoxia and hypoxia, and the subsequent reductions in oxygen saturation, were
      also similar with therapy using bosentan and placebo (p = 0.42). CONCLUSION: In
      healthy men, ET does not play an important role in peripheral chemoreceptor
      activation by acute hypoxia.

PMID- 17494796
TI  - Endogenous urate production augments plasma antioxidant capacity in healthy
      lowland subjects exposed to high altitude.
AB  - BACKGROUND: Both tissue hypoxia in vitro, and whole-body hypoxia in vivo, have
      been found to promote the release of reactive oxygen species (ROS) that are
      potentially damaging to the cardiovascular system. Antioxidant systems protect
      against oxidative damage by ROS and may exhibit some degree of responsiveness to
      oxidative stimuli. Production of urate, a potent soluble antioxidant, is
      increased in hypoxic conditions. We aimed to determine whether urate is an
      important antioxidant defense in healthy subjects exposed to hypoxia. METHODS: We
      conducted a cohort study of 25 healthy lowland volunteers during acute exposure
      to high altitude (4 days at 3,600 m, followed by 10 days at 5,200 m) on the Apex
      high-altitude research expedition to Bolivia. We measured markers of oxidative
      stress (8-isoprostane F2), serum urate concentration, and total plasma
      antioxidant activity by two techniques: 2,2'-amino-di-[3-ethylbenzthiazole
      sulfonate] spectrophotometry (total antioxidant status [TAS]) and enhanced
      chemiluminescence (ECL). RESULTS: On ascent, F2-isoprostane levels were
      significantly elevated compared with those at sea level (p < 0.01). After 1 week
      at high altitude, plasma antioxidant capacity (AOC) by both TAS and ECL, and
      serum urate concentration were significantly elevated (each p < 0.01 vs sea
      level), and F2-isoprostane levels were reduced to values at sea level. There was
      a highly significant correlation between plasma urate and AOC at this stage (ECL,
      r(2) = 0.59, p = 0.0001; TAS, r(2) = 0.30, p = 0.0062). CONCLUSIONS: Our results
      support the hypothesis that urate may act as a responsive endogenous antioxidant
      in high-altitude hypoxia.

PMID- 17494797
TI  - Acute effects of smoking on skeletal muscle microcirculation monitored by near
      infrared spectroscopy.
AB  - BACKGROUND: Cigarette smoking predisposes to vascular disease. Our study aimed to
      assess the acute effects of cigarette smoking on peripheral microcirculation
      using near-infrared spectroscopy (NIRS) and to compare microcirculatory function
      of smokers with that of nonsmokers. METHODS: We examined 65 healthy volunteers:
      25 smokers (14 men and 11 women; age range, 20 to 27 years) and 40 nonsmokers (31
      men and 9 women; age range, 19 to 38 years). Smokers had refrained from smoking
      for 2 h prior to the examination. Tissue O(2) saturation (Sto(2)), defined as the
      percentage of hemoglobin saturation in the microvasculature compartments, was
      measured with a probe placed on the thenar muscle. Sto(2) baseline values were
      recorded for 5 min. Subsequently, the brachial artery occlusion technique was
      applied to evaluate microcirculatory function before, during, and after smoking
      one cigarette. RESULTS: Sto(2) before smoking was 85 +/- 6% (mean +/- SD), not
      differing significantly between men and women (84.4 +/- 6.6% vs 85.6 +/- 5.8%,
      respectively; p = 0.721). Sto(2) did not change significantly during smoking.
      O(2) consumption rate was significantly greater in women (33.4 +/- 6.7 Sto(2)
      U/min vs 25.7 +/- 7.1 Sto(2) U/min, p = 0.032) at baseline and throughout the
      smoking session. O(2) consumption rate was reduced during smoking (p < 0.001) and
      at 5 min after the smoking session. Smoking had a significant effect on vascular
      reactivity (p = 0.015), with no significant differences between genders. Five
      minutes after smoking, vascular reactivity had returned to approximately normal
      levels. CONCLUSION: Smoking acutely affects microcirculatory function. NIRS is a
      noninvasive, operator-independent technique that can document these effects. It
      seems promising for the prospective evaluation of the effects of long-term
      exposure to cigarette smoke.

PMID- 17494798
TI  - Spirometer calibration checks: is 3.5% good enough?
AB  - BACKGROUND: Current standards for spirometry require daily calibration checks to
      come within 3.5% of the inserted volume but do not require evaluation of trends
      over time. We examined the current guidelines and candidate quality control rules
      to determine the best method for identifying spirometers with suboptimal
      performance. METHODS: Daily calibration checks on seven volume spirometers
      recorded over 4 to 11 years were reviewed. Current guidelines and candidate
      quality control rules were applied to determine how well each detected suboptimal
      spirometer performance. RESULTS: Overall, 98% of 7,497 calibration checks were
      within 3.5%. However, based on visual inspection of calibration check data plots,
      spirometers 3 and 5 demonstrated systematic sources of error, drift, and bias.
      The +/- 3.5% criteria did not identify these spirometers. The application of +/-
      2% criteria identified these spirometers (9% out-of control values in spirometers
      3 and 5 vs < 5% in other spirometers). A rule stipulating out-of-control
      conditions when four consecutive checks exceeded 1% deviation identified
      suboptimal spirometers (14% and 20% out-of-control values) but maintained low
      error detection rates in other spirometers (< or = 2%). Other candidate rules
      were less effective or required longer times to error detection. CONCLUSIONS: The
      current recommendation that calibration checks come within +/- 3.5% of the
      inserted volume did not detect subtle errors. Alternative candidate rules were
      more effective in detecting errors and maintained low overall error-detection
      rates. Our findings emphasize the need for laboratories to systematically review
      calibration checks over time and suggest that more stringent guidelines for
      calibration checks may be warranted for volume spirometers. Although our general
      approach may also be appropriate for flow-type spirometers, the details are
      likely to differ since flow-type spirometers are a much more varied category of
      equipment.

PMID- 17494799
TI  - Warfarin and antiplatelet combination use among commercially insured patients
      enrolled in an anticoagulation management service.
AB  - BACKGROUND: Although warfarin and antiplatelet medications have documented
      efficacy for prevention of primary and secondary cardiovascular events, the
      appropriateness of warfarin and antiplatelet combination therapy is not well
      described in national consensus guidelines. METHODS AND RESULTS: Cross-sectional
      data from 4,557 Kaiser Permanente Colorado members > or = 18 years old who were
      receiving warfarin anticoagulation therapy were used to quantify the prevalence
      of warfarin and antiplatelet agent (ie, aspirin, clopidogrel, dipyridamole,
      and/or dipyridamole/aspirin) combination therapy as of September 30, 2005, and to
      identify characteristics of patients receiving combination therapy. The
      prevalence of warfarin and any antiplatelet combination therapy was 385/1,000
      (95% confidence interval [CI], 371/1,000 to 399/1,000). The majority of
      combination therapy was warfarin and aspirin (prevalence, 378/1,000) with a daily
      dose of aspirin, 81 mg, being the most reported dose (prevalence, 328/1,000).
      Patients receiving combination therapy were more likely to be male (63.6% vs
      46.4%; adjusted odds ratio, 1.5; 95% CI, 1.3 to 1.7) and have a comorbidity of
      heart failure (29.0% vs 15.6%; adjusted odds ratio, 1.2; 95% CI, 1.1 to 1.5),
      coronary artery disease (62.4% vs 17.5%; adjusted odds ratio, 7.6; 95% CI, 6.5 to
      8.8), and/or stroke/transient ischemic attack (5.2% vs 1.6%; adjusted odds ratio,
      3.5; 95% CI, 2.3 to 5.3). CONCLUSION: Nearly 4 of 10 patients receiving warfarin
      management care were receiving warfarin and antiplatelet combination therapy. The
      findings suggest that this practice is widespread, especially among patients with
      established cardiovascular disease, and involves a substantially higher number of
      patients than previously reported. The clinical outcomes associated with this
      practice require further investigation.

PMID- 17494800
TI  - Solid or partly solid solitary pulmonary nodules: their characterization using
      contrast wash-in and morphologic features at helical CT.
AB  - BACKGROUND: Solitary pulmonary nodule (SPN) evaluation based on analyses of
      combined wash-in (WI) and washout (WO) values obtained by helical dynamic CT
      (HDCT) scanning is useful for malignant SPN characterization, because this method
      has higher specificity and accuracy than that based on analyses of WI values
      only. However, increased specificity results in reduced sensitivity and the
      missing of malignant SPNs. Thus, the purpose of this study was to seek the most
      effective method for SPN characterization during HDCT scanning. METHODS: After
      obtaining unenhanced CT scans, dynamic CT scanning was performed using a helical
      technique (images were obtained at 30, 60, 90, and 120 s, and at 5 and 15 min
      after the initiation of IV contrast administration) in 486 patients with a solid
      or partly solid SPN. Diagnostic efficacies were compared for three approaches
      involving considerations of WI values (in Housfield units [HU]) only, both WI and
      WO HU values, and WI HU values and morphologic characteristics. RESULTS:
      Considering WI values only (> or = 25 HU), sensitivity, specificity, and accuracy
      for malignancy were 98% (233 of 237 nodules), 46% (114 of 249 nodules), and 71%
      (347 of 486 nodules), respectively. Using both a WI value of > or = 25 HU and a
      WO value of 5 to 36 HU, the corresponding values were 89% (212 of 237 nodules),
      79% (197 of 249 nodules), and 84% (409 of 486 nodules), respectively; for a WI
      value of > or = 25 HU and a malignant morphology, the corresponding values were
      92% (219 of 237 nodules), 79% (197 of 249 nodules), and 86% (416 of 486 nodules),
      respectively (these values were significantly different between the WI-only group
      and the other two groups; p = 0.001). CONCLUSIONS: The efficacy of SPN evaluation
      based on analyses of WI values plus morphologic features during HDCT scanning
      appears to be equivalent to that based on analyses of WI plus WO values, thus
      obviating the need for WO scans, which saves time and reduces radiation exposure
      of the patient.

PMID- 17494801
TI  - A novel technique for localization of small pulmonary nodules.
AB  - BACKGROUND: To show the safety and accuracy of a new marking technique using an
      image-guided technique for preoperative localization of a small pulmonary nodule.
      METHODS: CT data of a patient with a peripheral pulmonary nodule < 20 mm were
      transmitted to a surgical navigation system (StealthStation Treon Treatment
      Guidance System; Medtronic; Louisville, KY). To match preoperative CT image data
      to the physical space occupied by the patient during surgery, five to six
      superficial skin fiducials were used for registration. A 16-gauge needle attached
      by a positioning sensor was advanced into or immediately adjacent to the nodule
      for injection of methylene blue under guidance of the StealthStation system. Then
      the lesion marked by the methylene was thoracoscopically resected. RESULTS:
      Seventeen patients (12 men and 5 women; mean age, 51.3 years) underwent this
      procedure, and all the nodules were identified due to the precise location of the
      probe. They were resected with sufficient margins. There were no surgical
      complications. The average time of registration was 4.8 +/- 0.9 min (+/- SD).
      Registration error was on average 2.7 +/- 0.2 mm. CONCLUSIONS: Image-guided
      navigation is useful, accurate, and safe in the localization of small peripheral
      lung lesions.

PMID- 17494802
TI  - The ethical foundations of professionalism: a sociologic history.
AB  - The purpose of this article is to trace the development of medical
      professionalism in medicine from its origins to the present. Codes of
      professional conduct are the tangible expressions of professionalism. I use them
      as a window into contemporary circumstances of medical practice. The medieval
      guilds are my framework for examining the relationship of the medical profession
      in relation to society. The craft guilds of postmedieval Europe wielded
      considerable power. They controlled entry into a craft, training, and standards
      of quality. By controlling the volume of production, they controlled price. The
      craft guilds flourished until their monopoly powers began to hinder the forces of
      capitalism, which influenced the state to limit the powers of the guild. The
      professions are the offspring of the medieval craft guilds. Since the early 19th
      century, the medical profession in the United States has sought guild powers. The
      triangular relationship between state, capitalism, and the medical profession
      explains the rise of the profession during the 19th century and its decline since
      the mid-20th century. I argue that the codes of conduct of the profession reflect
      what it needs to maintain its guild powers against the forces of capitalism and
      the state. The Charter on Medical Professionalism calls on physicians to take
      into account both the individual patient's needs and those of society. I believe
      this important clause reflects the conflict of the profession with the state and
      capitalism over the aggregate costs of medical care.

PMID- 17494803
TI  - ICU-acquired weakness.
AB  - Observational studies of patients receiving prolonged mechanical ventilation and
      other forms of critical care support have determined acquired neuromuscular
      disorders to be extremely common. Early studies used electrophysiologic
      investigations to diagnose critical illness polyneuropathy (CIP) and muscle
      biopsy to confirm critical illness myopathy (CIM). More recent approaches seek to
      obviate these invasive techniques and build on a standardized bedside
      neuromuscular examination to identify patients with acquired weakness syndromes.
      Serial examination in the alert patient may serve as a reasonable prognosticator
      for most patients. The importance of ICU-acquired weakness syndromes is supported
      by the observation that muscle wasting and weakness are among the most prominent
      long-term complications of survivors of ARDS. In addition, a strong association
      appears to exist between acquired weakness and protracted ventilator dependence,
      an important determinant of ICU length of stay. Multivariate analysis has
      identified several risk factors associated with increased incidence for ICU
      acquired weakness, including severe systemic inflammation, medications
      (specifically, corticosteroids and neuromuscular blocking agents), glycemic
      control, and immobility. We advocate an approach to this common syndrome that
      identifies risk factors early in the hope of minimizing their impact.

PMID- 17494804
TI  - Reducing the toll of inflammatory lung disease.
AB  - Toll-like receptors (TLRs) are pivotal in human response to microbial stimuli.
      Their activation and signaling underpin much of the observed epidemiologic data
      generated by the hygiene hypothesis, and their contribution to infectious
      exacerbations of airways disease is likely to be highly important. Our growing
      knowledge in this field will have a significant impact on the understanding of
      the pathogenesis of inflammatory diseases, and TLR-based therapies are already in
      early clinical trials to modify atopic disease severity.

PMID- 17494805
TI  - Systemic effects of smoking.
AB  - Smoking is one of the major lifestyle factors influencing the health of human
      beings. Life-long cigarette smokers have a higher prevalence of common diseases
      such as atherosclerosis and COPD with significant systemic impact. The present
      review evaluates current knowledge concerning possible pathways through which
      cigarette smoking can affect human health, with special focus on extrapulmonary
      effects. Long-term smoke exposure can result in systemic oxidants-antioxidants
      imbalance as reflected by increased products of lipid peroxidation and depleted
      levels of antioxidants like vitamins A and C in plasma of smokers. A low-grade
      systemic inflammatory response is evident in smokers as confirmed by numerous
      population-based studies: elevated levels of C-reactive protein (CRP),
      fibrinogen, and interleukin-6, as well as increased counts of WBC have been
      reported. Furthermore, rheologic, coagulation and endothelial function markers
      like hematocrit, blood and/or plasma viscosity, fibrin d-dimer, circulating
      adhesion molecules (intracellular adhesion molecule-1, selectins), tissue
      plasminogen activator antigen, and plasminogen activator inhibitor type I are
      altered in chronic cigarette smokers. Although most of smoking-induced changes
      are reversible after quitting, some inflammatory mediators like CRP are still
      significantly raised in ex-smokers up to 10 to 20 years after quitting,
      suggesting ongoing low-grade inflammatory response persisting in former smokers.
      New longitudinal epidemiologic and genetic studies are required to evaluate the
      role of smoking itself and possible gene/environment interplay in initiation and
      development of smoking-induced common diseases affecting humans.

PMID- 17494806
TI  - Elevated glucose in pleural effusion: an early clue to esophageal perforation.
AB  - Esophageal perforation is a rare cause of pleural effusions that carries with it
      a high mortality rate if diagnosis is delayed. The chemical characteristics of
      the pleural effusion include high amylase and low pH levels. However, these
      variables are nonspecific. We present a case of pleural effusion in a patient
      with markedly elevated glucose levels from recent cola ingestion as a specific
      clue to the diagnosis of esophageal perforation.

PMID- 17494807
TI  - Cardiac metastasis from lung adenocarcinoma causing atrioventricular block and
      left ventricular outflow tract obstruction.
AB  - Cardiac metastasis from lung cancer is rarely diagnosed antemortem, as it usually
      causes no symptoms or signs. We report the case of a 56-year-old man with
      recurrent lung adenocarcinoma in whom developed a large mass in the ventricular
      septum, complete atrioventricular block, and obstruction of the left ventricular
      outflow tract.

PMID- 17494808
TI  - Hypersensitivity pneumonitis-like syndrome associated with the use of
      lenalidomide.
AB  - Lenalidomide is an immunomodulatory agent approved for use in patients with
      myelodysplastic syndrome, and in combination with dexamethasone for refractory or
      relapsed multiple myeloma. Pulmonary toxicity is believed to be uncommon. In this
      report, we describe a patient receiving lenalidomide in whom dyspnea, fever,
      hypoxia, and diffuse pulmonary infiltrates developed. BAL demonstrated a
      significant lymphocytic alveolitis typical for hypersensitivity pneumonitis.
      Extensive workup for other causes, including infections, was negative. Finally,
      the patient had improvement in symptoms and oxygenation after withdrawing
      lenalidomide and recurrence of symptoms when the drug was restarted. Thus, the
      patient's clinical course and workup strongly support a diagnosis of lenalidomide
      induced hypersensitivity pneumonitis-like syndrome. Physicians should be
      cognizant of this potential complication in patients receiving thalidomide or
      thalidomide-like drugs who present with fever and pulmonary infiltrates and fail
      to improve despite treatment with broad-spectrum antibiotics.

PMID- 17494809
TI  - Pulmonary hypertension due to a retained totally implantable venous access device
      fragment.
AB  - Pulmonary hypertension can occur from obstruction of the distal pulmonary
      arteries by thrombus, ova and parasites, and foreign material. We report a 62
      year-old patient who had fatal pulmonary hypertension from an 8-cm fragment of a
      totally implantable venous access device (TIVAD) retained in the pulmonary
      artery. Despite long-term therapeutic anticoagulation, pulmonary angiography
      showed chronic occlusion of the posterior branch of the superior right pulmonary
      artery with paucity of distal vasculature consistent with an old right upper lobe
      pulmonary embolus. Retrieval of the fragment was attempted via pulmonary artery
      catheterization techniques but was unsuccessful. In conclusion, progressive
      pulmonary hypertension may result from retention of a TIVAD fragment in a central
      pulmonary artery despite therapeutic anticoagulation. Worsening pulmonary
      hypertension may have been due to partial obstruction of the main pulmonary
      arteries, resulting in recurrent thromboembolism or in situ thrombosis, and
      remodeling of small distal pulmonary arteries.

PMID- 17494810
TI  - Surfactant replacement therapy.
AB  - Surfactant replacement therapy (SRT) has a proven role in the treatment of
      neonatal respiratory distress syndrome and severe meconium aspiration syndrome in
      infants, and may have a role in the treatment of pediatric patients with ARDS.
      Although newer delivery mechanisms and strategies are being studied, the classic
      surfactant administration paradigm consists of endotracheal intubation,
      surfactant instillation into the lung, and stabilization with mechanical
      ventilation followed by extubation when stable on low respiratory support.
      Currently, this surfactant administration procedure is bundled into Current
      Procedural Terminology (CPT) codes used when providing intensive care. A specific
      CPT code for surfactant administration is scheduled to be introduced in 2007.
      This article reviews clinical issues in SRT and the practice management
      considerations necessary to provide this care.

PMID- 17494811
TI  - Controversies in RBC transfusion in the critically ill.
AB  - Transfusion practice has been under great scrutiny over the last 2 decades. The
      examination of transfusion risks and benefits have been particularly important in
      the critically ill patient population. This review will examine some of the
      important controversies still surrounding the use of RBC transfusion in the
      critically ill patient.

PMID- 17494812
TI  - Avoiding common problems during online submission of manuscripts.
AB  - Online submission of manuscripts is normally fast, relatively easy, and timely.
      However, failure to follow journal instructions, omitting required aspects of
      manuscripts, and other problems can delay or stop the submission and peer-review
      process. This article discusses common problems encountered during online
      submission and advises authors on how to avoid those problems and maximize the
      efficiency of the online submission process.

PMID- 17494813
TI  - A 42-year-old woman with sudden onset of back pain and severe dyspnea.

PMID- 17494814
TI  - An unusual cause of cough and dyspnea in an immunocompromised patient.

PMID- 17494815
TI  - A 51-year-old woman with blanched skin, coagulopathy, abdominal pain, and
      cardiopulmonary failure.

PMID- 17494816
TI  - A patient with sickle cell disease with septic shock, purpura, and cold
      extremities.

PMID- 17494817
TI  - Clinicians' competency in bioethics.

PMID- 17494818
TI  - Analytical shortfalls in multivariate regression analysis.

PMID- 17494819
TI  - Effect of work hour restrictions on fellows.

PMID- 17494820
TI  - Risk factors for extubation success in patients following failure of a
      spontaneous breathing trial.

PMID- 17494821
TI  - There are no excuses for not performing spirometry in acute asthmatics in the
      emergency department setting.

PMID- 17494822
TI  - Sister Leena's sign: a sign that may be useful in differentiating colopleural
      fistula (fecal empyema) from usual empyema.

PMID- 17494823
TI  - The role of hypnotics in continuous positive airway pressure compliance.

PMID- 17494825
TI  - Pulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based Clinical Practice
      Guidelines.
AB  - BACKGROUND: Pulmonary rehabilitation has become a standard of care for patients
      with chronic lung diseases. This document provides a systematic, evidence-based
      review of the pulmonary rehabilitation literature that updates the 1997
      guidelines published by the American College of Chest Physicians (ACCP) and the
      American Association of Cardiovascular and Pulmonary Rehabilitation. METHODS: The
      guideline panel reviewed evidence tables, which were prepared by the ACCP
      Clinical Research Analyst, that were based on a systematic review of published
      literature from 1996 to 2004. This guideline updates the previous recommendations
      and also examines new areas of research relevant to pulmonary rehabilitation.
      Recommendations were developed by consensus and rated according to the ACCP
      guideline grading system. RESULTS: The new evidence strengthens the previous
      recommendations supporting the benefits of lower and upper extremity exercise
      training and improvements in dyspnea and health-related quality-of-life outcomes
      of pulmonary rehabilitation. Additional evidence supports improvements in health
      care utilization and psychosocial outcomes. There are few additional data about
      survival. Some new evidence indicates that longer term rehabilitation,
      maintenance strategies following rehabilitation, and the incorporation of
      education and strength training in pulmonary rehabilitation are beneficial.
      Current evidence does not support the routine use of inspiratory muscle training,
      anabolic drugs, or nutritional supplementation in pulmonary rehabilitation.
      Evidence does support the use of supplemental oxygen therapy for patients with
      severe hypoxemia at rest or with exercise. Noninvasive ventilation may be helpful
      for selected patients with advanced COPD. Finally, pulmonary rehabilitation
      appears to benefit patients with chronic lung diseases other than COPD.
      CONCLUSIONS: There is substantial new evidence that pulmonary rehabilitation is
      beneficial for patients with COPD and other chronic lung diseases. Several areas
      of research provide opportunities for future research that can advance the field
      and make rehabilitative treatment available to many more eligible patients in
      need.

PMID- 17494826
TI  - ODD, ADHD, versus ODD+ADHD in clinic and community adults.
AB  - OBJECTIVE: To seek evidence for the validity of oppositional defiant disorder
      (ODD) as a behavioral syndrome in adults. METHOD: Two samples of adults, mental
      health outpatient clinic referrals (N = 490) and community controls (N = 900),
      completed a Diagnostic and Statistic Manual of Mental Disorders-referenced rating
      scale and a brief questionnaire (social, educational, occupational, and treatment
      variables). Participants were separated into four groups: ODD-only, ADHD-only,
      ODD+ADHD, and NONE. RESULTS: In general, the three symptom groups were more
      severe than the NONE group; the ODD+ADHD and NONE groups were the most and least
      severe, respectively; and there were clear differences between the ODD-only and
      ADHD-only groups. The pattern of group differences was generally similar in both
      samples. CONCLUSION: Findings support the distinction between ADHD and ODD
      symptom presentations in adults, and the notion that the comorbid condition is a
      unique clinical entity, both of which are consistent with the child literature.
      Nevertheless, additional research with larger samples of patients will be
      necessary to establish ODD as a potential behavioral syndrome in adults.

PMID- 17494827
TI  - Growing out of ADHD: the relationship between functioning and symptoms.
AB  - OBJECTIVE: The objective is to ascertain whether people in partial remission
      (IPR) or in full remission (IR) of their ADHD symptoms continue to have
      neuropsychological deficits and clinical and psychosocial problems. METHOD: IPR
      and IR groups are compared with fully symptomatic ADHD patients and normal
      controls. RESULTS: The results show a decline across the patient groups
      indicating that symptom remission is associated with improvement in
      neuropsychological, clinical, and psychosocial problems. The two symptomatic
      (ADHD and IPR) groups have the most marked psychosocial and drug-related
      problems, and they seem to continue to attempt to access help by presenting to
      adult psychiatric services. However, the IR group continues to have
      neuropsychological problems in comparison to the normal controls. CONCLUSION:
      Neuropsychological functioning, clinical, and psychosocial problems seem to be
      closely associated with ADHD symptoms and improve steadily with remission.
      However, some residual problems persist for which the patients seek psychiatric
      help.

PMID- 17494828
TI  - Psychiatric comorbidity in ADHD symptom subtypes in clinic and community adults.
AB  - OBJECTIVE: To compare psychiatric comorbidity between the three symptom subtypes
      of Attention-Deficit/Hyperactivity Disorder (ADHD), Inattentive (I), Hyperactive
      Impulsive (H), and Combined (C), in adults. METHOD: A clinic sample (N = 487) and
      a nonreferred community sample (N = 900) completed a DSM-IV-referenced rating
      scale and a questionnaire (social, educational, occupational, and treatment
      variables). Participants were assigned to one of four groups: ADHD:I, ADHD:H,
      ADHD:C, and NONE. RESULTS: All three ADHD symptom groups reported more severe
      comorbid symptoms than the NONE group; the ADHD:C and NONE groups were the most
      and least severe, respectively; and there were clear differences between the
      ADHD:I and ADHD:H groups. The pattern of group differences was similar in both
      samples. CONCLUSION: ADHD symptom subtypes in adults are associated with distinct
      clinical correlates. The diversity of self-reported psychopathology in adults who
      meet symptom criteria for ADHD highlights the importance of conducting broad
      based evaluations.

PMID- 17494829
TI  - Atypical brain activation during simple & complex levels of processing in adult
      ADHD: an fMRI study.
AB  - OBJECTIVE: Executive dysfunction in ADHD is well supported. However, recent
      studies suggest that more fundamental impairments may be contributing. We
      assessed brain function in adults with ADHD during simple and complex forms of
      processing. METHOD: We used functional magnetic resonance imaging with forward
      and backward digit spans to investigate number repetitions and complex working
      memory function. If pathology is limited to higher cognitive operations, group
      differences should be confined to the backward condition. RESULTS: During the
      forward digit span, ADHD participants exhibited greater activation of LH
      linguistic processing areas and increased activation of right frontal and
      parietal cortices. During the backward digit span, they exhibited greater
      activation of LH linguistic processing areas and failed to activate bilateral
      parietal regions important for the complex executive operations. CONCLUSION:
      Abnormal brain function among adult ADHD participants was not limited to complex
      executive functions. Abnormal processing of numeric stimuli was indicated during
      both simple and complex cognitive operations.

PMID- 17494830
TI  - Sibling relationships among children with ADHD.
AB  - OBJECTIVE: This study investigated the quality of sibling relationships among
      children with ADHD relative to those without ADHD. Additional analyses examined
      whether externalizing and internalizing problems comorbid with ADHD affected
      sibling relationships. METHOD: Participants were 77 children with ADHD and 14
      nonproblem control children. Sibling relationships were assessed via three
      informants: mother report, self-report, and sibling report. RESULTS: In analyses
      utilizing hierarchical linear modeling to combine data from the three informants,
      children with ADHD showed increased conflict in sibling relationships, relative
      to nonproblem children. Comorbid externalizing problems were associated with less
      warmth/ closeness and increased conflict in the sibling relationship and largely
      accounted for the finding that children with ADHD showed greater sibling
      relationship problems. Comorbid internalizing problems were associated with less
      warmth/closeness in the sibling relationship. CONCLUSION: It is recommended that
      sibling relationships be incorporated into theories of social impairment in ADHD.

PMID- 17494831
TI  - Inhibitory control of proactive interference in adults with ADHD.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is associated with
      poor inhibition of prepotent responses and deficits in distractor inhibition, but
      relatively few studies have addressed inhibitory control of proactive
      interference (PI) in individuals with ADHD. Thus, the goal of the present study
      was to evaluate resistance to spatial and verbal PI in adults with ADHD. METHOD:
      Adults with ADHD (n = 32) and adults without ADHD (n = 32) performed a spatial
      inhibition of return (IOR) task and a semantic IOR task. RESULTS: Adults with and
      without ADHD showed effective spatial IOR. On the semantic IOR task, adults
      without ADHD showed semantic inhibition, whereas adults with ADHD showed semantic
      facilitation (positive priming) instead. CONCLUSION: Adults with ADHD may have
      domain-specific deficits in resistance to proactive interference. Research has
      theoretical and clinical implications for adults with ADHD.

PMID- 17494832
TI  - Relations between the Test of Variables of Attention (TOVA) and the Children's
      Memory Scale (CMS).
AB  - OBJECTIVE: There is considerable overlap in the constructs of attention and
      memory. The objective of this study was to examine the relationship between the
      Test of Variables of Attention (TOVA), a measure of attention, to components of
      memory and learning as measured by the Children's Memory Scale (CMS). METHOD:
      Participants (N = 105) were consecutive referrals to an out-patient facility,
      generally for learning or behavior problems, who were administered both the TOVA
      and the CMS. RESULTS: Significant correlations were found between the omissions
      score on the TOVA and subscales of the CMS. TOVA variability and TOVA reaction
      time correlated significantly with subscales of the CMS as well. TOVA commission
      errors did not correlate significantly with any CMS Index. CONCLUSION: Although
      significant, the correlation coefficients indicate that the CMS and TOVA are
      measuring either different constructs or similar constructs but in different
      ways. As such, both measures may be useful in distinguishing memory from
      attention problems.

PMID- 17494833
TI  - An analysis of patient adherence to treatment during a 1-year, open-label study
      of OROS methylphenidate in children with ADHD.
AB  - OBJECTIVE: Treatment adherence is an important aspect of ADHD symptom management,
      but there are many factors that may influence adherence. METHOD: This analysis
      assessed adherence to OROS methylphenidate during a 1-year, open-label study in
      children. Adherence was defined as the number of days medication was taken
      divided by the number of days in the study and determined to be high if > or
      =75%. Possible clinical and demographic factors associated with adherence,
      including use of planned medication breaks, were assessed. RESULTS: Mean
      adherence was 86.4%. It was 91.6% for the subgroup of patients who reported not
      taking planned medication breaks (n = 252) and 77.7% for the subgroup taking
      planned medication breaks (n = 155). Overall, 75% of patients showed high
      adherence. Older age, low starting dose, minority ethnic status, and fewer ADHD
      symptoms were associated with low adherence. CONCLUSION: Various factors were
      found to be associated with low adherence, and the results of this analysis
      provide guidance to physicians seeking to identify those patients with ADHD most
      likely not be adherent to stimulant therapy

PMID- 17494834
TI  - Monitoring quality of life in adults with ADHD: reliability and validity of a new
      measure.
AB  - OBJECTIVE: To develop and evaluate a questionnaire, the ADHD Impact Module for
      Adults (AIM-A), to dimension quality of life for adults with attention
      deficit/hyperactivity disorder (ADHD). METHOD: Six multi-item AIM scales were
      developed and evaluated in 317 participants enrolled in an open-label trial.
      Multitrait scaling analysis and correlations between the AIM-A and the ADHD
      Rating Scale were evaluated. Differences in scale scores based on severity
      (clinician rated), subtype, previous medication experience, and sensitivity to
      change were examined, and F statistics were compared for the AIM-A and the ADHD
      Rating Scale. RESULTS: 100-80% scaling successes were observed for the AIM-A
      scales. Alpha coefficients were >or=.83. Significant correlations were observed
      (range: .494 to .200). The AIM-A discriminated based on severity, subtype, and
      medication experience (p <or= .01) and was sensitive to change (n = 23, p <or=
      .001). CONCLUSION: Psychometric findings are encouraging. Future efforts will
      examine validity and responsiveness in larger clinical samples with different
      therapeutic interventions.

PMID- 17494835
TI  - CBCL clinical scales discriminate ADHD youth with structured-interview derived
      diagnosis of oppositional defiant disorder (ODD).
AB  - OBJECTIVE: To evaluate the association between the clinical scales of the child
      behavior checklist (CBCL) and the comorbid diagnosis of oppositional defiant
      disorder (ODD) in a large sample of youth with attention deficit hyperactivity
      disorder (ADHD). METHOD: The sample consisted of 101 girls and 106 boys ages 6
      to17 with ADHD. Conditional probability analysis was used to examine the
      correspondence between CBCL Clinical Scales with the structured-interview derived
      diagnosis of ODD. RESULTS: Conditional probability analysis showed that the CBCL
      Aggression Scale best predicted a structured-interview derived diagnosis of ODD
      in boys and girls with ADHD. CONCLUSION: These findings suggest that the CBCL
      Aggression Scale could serve as a rapid and cost-effective screening instrument
      to help identify cases likely to meet clinical criteria for ODD in the context of
      ADHD

PMID- 17494836
TI  - Early grade repetition and inattention associated with neurofibromatosis type 1.
AB  - OBJECTIVE: The authors analyze the occurrence of grade repetition and inattention
      in children diagnosed with neurofibromatosis type 1 (NF1). METHOD: The
      participant group consisted of 310 patients with NF1 and a control group of 242
      individuals. The number of grade repetitions for each participant during his or
      her time in elementary, middle, and high school was noted and the inattention
      score was calculated from the Barkley's ADHD Clinic Parent Interview form.
      RESULTS: Fifty-three percent of NF1 patients versus 25% of the controls had
      increased grade repetition, P2 (1) = 27.41, p < .0001, and 67% of NF1 patients
      versus 14% of controls were found to be inattentive, 2 (1) = 27.41, p < .0001.
      Repetition mainly affected kindergarten and first-grade levels and the
      inattention score significantly correlated with grade repetition prevalence in
      NF1 patients (r2 = .7429, p < .0004). CONCLUSION: Grade repetition is a frequent
      complication in NF1 and correlates with inattention in individuals with this
      disease.

PMID- 17494837
TI  - Novel stable camptothecin derivatives replacing the E-ring lactone by a ketone
      function are potent inhibitors of topoisomerase I and promising antitumor drugs.
AB  - The E-ring lactone is the Achilles' heel of camptothecin derivatives: although it
      is considered necessary for the inhibition of the enzyme topoisomerase I (topo1),
      the opening of the lactone into a carboxylate abolishes the generation of topo1
      mediated DNA breaks. S38809 is a novel camptothecin analog with a stable 5
      membered E-ring ketone; therefore, it lacks the lactone function. DNA relaxation
      and cleavage assays revealed that S38809 functions as a typical topo1 poison by
      stimulating DNA cleavage at T downward arrow G sites. The activity was strongly
      dependent on the stereochemistry of the C-7 carbon atom that bears the hydroxy
      group. S38809 proved to be a potent cytotoxic agent, with a mean IC50 of 5.4 nM
      versus 11.6 nM for topotecan and 3.3 nM for SN38 (the active metabolite of
      irinotecan) on a panel of 31 human tumor cell lines. The cytotoxicity of S38809
      and its ability to stabilize cleavable complexes was considerably reduced in
      camptothecin-resistant cells that express a mutated topo1, confirming that topo1
      is its primary target. Cell death induced by topo1 poisoning requires the
      conversion of DNA single-strand breaks into double-strand breaks that can be
      detected by the formation of phosphorylated histone H2AX. In HCT116 cells,
      topotecan, SN38, and S38809 induced histone H2AX phosphorylation in S phase of
      the cell cycle, with S38809 being as potent as SN38 and 5-fold more potent than
      topotecan. In vivo, S38809 showed a marked antitumor activity against HCT116
      xenografts. These findings open a new route for improving the pharmacological
      properties of camptothecin derivatives.

PMID- 17494838
TI  - Critical mass: the potential role of the mega-group to address the manpower
      shortage and facilitate office-based practice in interventional radiology.

PMID- 17494839
TI  - Endovascular management of major arterial hemorrhage as a complication of
      inflammatory pancreatic disease.
AB  - PURPOSE: Major arterial hemorrhage is an important complication of inflammatory
      pancreatic disease, with an overall mortality of 37%. The present study was
      undertaken to evaluate the experience of a tertiary referral center for
      pancreaticobiliary disease in the management of major arterial complications of
      pancreatitis with selective visceral angiography and transcatheter arterial
      embolization (TAE). MATERIALS AND METHODS: A 6-year retrospective analysis of all
      patients undergoing visceral angiography for major bleeding as a complication of
      pancreatitis identified 35 patients (26 male, 9 female) with a mean age of 51.2
      years (range, 11-73 y). Patient demographics, history, clinical presentation,
      angiographic findings, angiographic treatment, and follow-up outcomes were
      retrospectively noted. Technical success was defined as the devascularization of
      a focal lesion or reduction or cessation of blood flow to a target vascular bed
      or organ, and clinical success was defined as the resolution of the symptoms and
      signs that prompted the initial embolization. RESULTS: Angiography identified the
      site of bleeding in 54.3% of patients (n=19) and angiographic intervention was
      performed in 77.1% of patients (n=27). Technical success was achieved in 81.5% of
      those 27 patients (n=22), with overall clinical success in 80.0% (n=28). Multiple
      angiograms were required in 12 patients, with four demonstrating bleeding from
      new sites. The mortality rate was 20% (7 of 35). CONCLUSIONS: In major arterial
      hemorrhage resulting from pancreatic inflammatory disease, visceral angiography
      can identify the site of bleeding and hemostasis can be achieved. Repeat
      angiography is often required with bleeding from new sites. The mortality rate is
      comparable to that associated with surgery and reflects multisystem involvement
      in acute severe pancreatitis.

PMID- 17494840
TI  - Percutaneous interventions in subclavian artery-to-contralateral subclavian vein
      "necklace" hemodialysis grafts: experience in five patients.
AB  - PURPOSE: To describe clinical outcomes of endovascular interventions in the
      setting of thrombosis or dysfunction of anterior chest wall ("necklace")
      arteriovenous (AV) hemodialysis grafts. MATERIALS AND METHODS: Eight percutaneous
      interventions (balloon angioplasty, pharmacologic thrombolysis, and mechanical
      thrombectomy) were performed in five patients with anterior chest wall AV grafts.
      Primary, assisted, and secondary patencies, as well as technical success and
      complication rates, were determined. RESULTS: The technical success rate of
      percutaneous interventions in re-establishing a normal blood flow pattern within
      the AV grafts was 100%. Primary patency ranged from one to 23 months (median, 5
      months). Primary assisted patency and secondary patency were 36 months and 8
      months, respectively, in two patients who underwent more than one intervention.
      Postintervention access patency ranged from 5 to 36 months (median, 9 months),
      whereas graft lifetime ranged from 12 to 45 months (median, 24 months). There
      were no complications related to revascularization procedures. CONCLUSION:
      Percutaneous interventions can be performed safely and effectively in anterior
      chest wall AV grafts. Technical success and long-term patency rates appear to be
      similar to those of percutaneous interventions in upper-extremity hemodialysis AV
      grafts.

PMID- 17494841
TI  - Evaluation of renal transplant donors with 16-section multidetector CT
      angiography: comparison of contrast media with low and high iodine
      concentrations.
AB  - PURPOSE: To compare the degree of contrast enhancement, image quality, and
      accuracy of renal computed tomographic (CT) angiography performed with a 16
      detector row CT unit and equal iodine doses of low- and high-iodine-concentration
      contrast medium in the evaluation of renal transplant donors. MATERIALS AND
      METHODS: Eighty donors scheduled to undergo renal CT angiography with 16-detector
      row CT were administered nonionic contrast media with two iodine concentrations.
      The first group (group A, n=40) received a contrast medium with 300 mg of iodine
      per milliliter, and the second group (group B, n=40) received a contrast medium
      with 370 mg of iodine per milliliter. An equal iodine dose of 550 mg per kilogram
      body weight was given to both groups. Contrast enhancement was quantified by
      measuring attenuation in the abdominal aorta and in both renal arteries.
      Subjective assessment of contrast enhancement, quality of reformatted images, and
      visualization of branch order of renal arteries were rated with a 5-point scale.
      The number of renal arteries and veins seen at CT was correlated with the results
      at surgery. RESULTS: The mean enhancement values in group B were significantly
      greater (P<.001) than those in group A. The mean HU (+/-standard deviation) in
      groups A and B were 298+/-76 and 344+/-75, respectively, in the aorta, 284+/-74
      and 331+/-71 in the right renal artery, and 285+/-72 and 329+/-73 in the left
      renal artery. The mean enhancement, image quality, and branch orders visualized
      were rated better in group B than in group A (P<.01). The accuracies for
      correctly identifying renal arteries and veins, respectively, were 91% and 95%
      for group A and 96% and 96% for group B. CONCLUSION: Renal donor CT angiography
      with a contrast medium of 370 mg of iodine per milliliter provides greater
      enhancement and image quality compared with a contrast medium of 300 mg of iodine
      per milliliter. The diagnostic accuracies were similar.

PMID- 17494842
TI  - Hepatocellular carcinoma with internal mammary artery supply: feasibility and
      efficacy of transarterial chemoembolization and factors affecting patient
      prognosis.
AB  - PURPOSE: To determine technical feasibility, therapeutic efficacies, and identify
      prognostic factors in patients with hepatocellular carcinoma (HCC) treated by
      transarterial chemoembolization via the internal mammary artery. MATERIALS AND
      METHODS: From August 1996 to July 2005, the authors identified the internal
      mammary arteries supplying HCCs in 97 (2.2%) of 4,438 HCC patients. Computed
      tomography scans and digital subtraction angiography images of these 97 patients
      were retrospectively reviewed by consensus between two of the authors regarding
      technical success and clinical outcome. The technical success of internal mammary
      artery chemoembolization was defined as achievement of catheterization into
      feeding vessels, delivery of drugs via those vessels, and no residual tumor
      staining fed by the internal mammary artery. Multivariate Cox proportional hazard
      regression analysis was performed to enable evaluation of prognostic factors for
      survival. RESULTS: Technical success by selective chemoembolization via internal
      mammary artery was achieved in 53 (55%) of the 97 patients. The clinical
      responses of the 97 patients were complete remission (n=3), partial remission
      (n=19), no response (n=65), and no available follow-up image (n=10). Overall
      cumulative survival rates, calculated from times of internal mammary artery
      chemoembolization, were 55.9% (at 6 months), 32.5% (at 1 year), 15.4% (at 2
      years), and 8.2% (at 3 years). Multivariate analysis showed that tumor
      multiplicity (single vs multiple nodular or diffuse; P=.013), portal vein
      thrombosis (P=.004), and the technical success of internal mammary artery
      chemoembolization (P=.02) each significantly affected survival. CONCLUSIONS:
      Although patients with HCC supplied by the internal mammary artery had poor
      prognosis because of their advanced stage of disease, chemoembolization via the
      internal mammary artery is possible and worth performing in selective situations.

PMID- 17494843
TI  - 90Y radioembolization of metastatic breast cancer to the liver: toxicity, imaging
      response, survival.
AB  - PURPOSE: To present data from patients with breast cancer liver metastases who
      underwent radioembolization with yttrium (90Y) microspheres. MATERIALS AND
      METHODS: Using standard 90Y lobar treatment protocol, 27 female patients with
      progressing liver metastases on standard of care polychemotherapy were treated
      under an open-label phase 2 protocol. After treatment, we assessed (a) tumor
      response using computed tomography and/or positron emission tomography, (b)
      biochemical toxicity, and (c) survival. RESULTS: The mean age of the patients was
      52. Seventeen (63%) patients received 20 left lobe treatments (median radiation
      dose, 123 Gy; mean, 119 Gy), and 20 (74%) patients received 22 right lobe
      treatments (median radiation dose, 121 Gy; mean, 109 Gy) to the treatment site.
      No significant dose-difference was noted between the two lobes (P=.69). Tumor
      response on 90-day follow-up computed tomography showed (a) complete and partial
      response in nine (39.1%) patients, (b) stable disease in 12 (52.1%) patients, and
      (c) progressive disease in 2 (8.8%) patients. Positive tumor response on positron
      emission tomography was noted in 17 (63%) patients. Three of 27 (11%) patients
      (Eastern Cooperation Oncology Group 1, 2, or 3) showed bilirubin toxicity of
      grade 3, all of which were attributed to disease progression. Median survival for
      Eastern Cooperation Oncology Group 0 versus 1, 2, or 3 patients was 6.8 months
      and 2.6 months, respectively (P=.24) and for patients with tumor burden<25%
      versus >25% was 9.4 and 2.0 months, respectively (P=.46). CONCLUSIONS:
      Radioembolization with 90Y brachytherapy device may be a viable therapeutic
      option for the treatment of breast cancer liver metastases in patients who have
      progressed or failed on standard of care polychemotherapy.

PMID- 17494844
TI  - Endobronchial stent placement for the management of airway complications after
      lung transplantation.
AB  - PURPOSE: To retrospectively evaluate the efficacy and complications of
      endobronchial stent placement for the management of airway complications
      following lung transplant. MATERIALS AND METHODS: From 1992 to 2003,
      tracheobronchial stenting was performed on 25 lung transplant recipients (16 male
      and 9 female; mean age 51.6 years; range 21-65 years). A total of 27 lesions were
      treated and 27 stents were deployed (nine bronchomalacia, 12 bronchial stenosis,
      three bronchial stenosis and bronchomalacia both and three anastomotic
      dehiscence). The clinical and bronchoscopic follow-up ranged from 1 month to 69
      months. RESULTS: The technical success was 100%. Eighty-four percent of patients
      had immediate relief in dyspnea. The overall complication rate following stent
      placement was 0.049 per patient per month (23 complications/471 patient months).
      Stent migration and granulation tissue formation were the most frequent
      complications. The mean percentage change in FEV-1 was significantly greater than
      zero at 1 month and 6 months (P<.05) post-stent placement. The mean percentage
      change in FEV-1 was marginally greater than zero at 12 months (P=.07).The mean
      percentage change in FVC was marginally greater than zero at 1 month and 6 months
      (P=.08) post-stent. It was not significantly greater than zero at 12 months
      (P=1.00). CONCLUSION: Tracheobronchial stent placement provides effective
      palliation of postoperative airway complications in lung transplant with
      morbidity that can be managed effectively by available treatment options. Airway
      stenting may be used as a primary management option for airway complications
      after lung transplantation as a large number of patients are not suitable
      candidates for repeat surgery.

PMID- 17494845
TI  - Awareness of interventional radiology among patients referred to the
      interventional radiology department: a survey of patients in a large Canadian
      community hospital.
AB  - PURPOSE: To quantify the level of knowledge about interventional radiology (IR)
      among patients referred for an IR procedure and to develop recommendations on how
      to increase public awareness of IR. MATERIALS AND METHODS: Paper surveys were
      prospectively administered to consecutive patients scheduled to undergo an IR
      procedure at a community hospital. The study was terminated at the accrual of 100
      completed surveys. RESULTS: Totals of 28% and 6% knew generally the job of a
      diagnostic radiologist and interventional radiologist, respectively, and 6% had
      heard of the field of IR before their referral (despite 21% having undergone a
      procedure previously). Before their arrival in the IR department, 87% had not
      received any information about IR. Three percent, 0%, 4%, 82%, and 82% had heard
      about uterine artery embolization, radiofrequency ablation, vertebroplasty,
      biopsy (any type), and angioplasty, respectively. After the procedures, 84% had a
      clearer view of what interventional radiologists do, but 98% believed that most
      others did not know what IR was. When asked how best to educate the public about
      IR, the responses were: unsure (39%), other (19%), pamphlets (12%), information
      from physicians (9%), television (8%), and Internet (7%). Overall, the mean
      satisfaction rate was 8.8 (with 0 representing the minimum and 10 representing
      the maximum), and 97% would choose IR over surgery for future treatments.
      CONCLUSIONS: These data quantify and strongly support the views that (1) even
      among patients specifically referred to IR for a procedure, the majority of
      people are unaware of what the field is or may offer; and (2) most patients were
      satisfied with their IR experience. Six results-based recommendations are made to
      increase public awareness about IR.

PMID- 17494846
TI  - Effect of transcatheter arterial embolization on levels of hypoxia-inducible
      factor-1alpha in rabbit VX2 liver tumors.
AB  - PURPOSE: To test the hypothesis that transcatheter arterial embolization (TAE) of
      VX2 rabbit liver tumors increases the expression of hypoxia-inducible factor
      1alpha (HIF-1alpha), a transcription factor that regulates the expression of pro
      angiogenic genes. MATERIALS AND METHODS: VX2 tumors were implanted in the livers
      of eight New Zealand white rabbits. Once tumor growth was seen at T2-weighted
      turbo spin-echo magnetic resonance (MR) imaging, four of the eight rabbits
      underwent TAE with 45-150-mum polyvinyl alcohol particles. The remaining four
      rabbits served as non-TAE controls. The TAE end point was stasis of antegrade
      blood flow. All rabbits were sacrificed for tumor harvest 2 hours after TAE.
      Tumor tissue and corresponding normal liver tissue in each rabbit liver were
      stained with anti-human HIF-1alpha monoclonal antibody and reviewed with light
      microscopy. Percentages of stained viable tumor and normal liver cells were
      compared by using the Mann-Whitney U test (alpha=0.05). RESULTS: In eight rabbits
      with 24 discrete liver tumors, the mean percentage (+/-standard deviation) of
      positive HIF-1alpha-stained cells in the TAE group was greater than that in the
      control group (19%+/-7.0 vs 12%+/-8.0, respectively) (P=.05). Normal liver tissue
      in both the TAE and control groups showed no HIF-1alpha staining. CONCLUSION:
      Although HIF-1alpha is not expressed in normal rabbit liver parenchyma-even after
      TAE-HIF-1alpha expression is present in implanted VX2 rabbit liver tumors and
      significantly increased in lesions that have undergone embolization.

PMID- 17494847
TI  - Radiofrequency ablation: variability in heat sensitivity in tumors and tissues.
AB  - PURPOSE: To characterize the thermal dosimetry (ie, heating profile) of
      radiofrequency ablation (RFA) in multiple ex vivo tissues and in vivo tumor
      models. MATERIALS AND METHODS: RFA was performed for 3-24 minutes in ex vivo
      bovine livers (n=20), porcine kidneys (n=20), and turkey muscles (n=20) and in
      vivo canine venereal sarcomas (n=8). RFA was performed by using 1 and 3-cm long
      tips internally cooled electrodes. In addition, RFA was performed in in vivo
      R3220 rat mammary adenocarcinomas (n=36) and human renal cell carcinomas in nude
      mice (n=6) by using 1-cm monopolar electrodes. Continuous temperature monitoring
      was performed at multiple depths to calculate thermal dosimetry, reported as the
      area under the curve (AUC). Cumulative equivalent minutes at 43 degrees C (CEM43)
      were used for the critical ablation margin. Data were compared with analysis of
      variance and regression analysis. RESULTS: For each tissue and/or tumor type,
      statistically significant temperature differences (up to 14 degrees) were
      observed at the ablation margin (P<.01). Temperature was dependent on the
      procedure duration. For 10-minute treatments, temperatures were significantly
      higher in the kidney compared with the R3230 tumor (72 degrees C+/-2.2) (P<.01)
      and lower in R3230 tumor (41.6 degrees C+/-1.4) (P<.05) but were similar for
      liver and muscle (51.6 degrees C+/-1.6 and 54.1 degrees C+/-1.8, respectively).
      Thus, a wide range of ablative temperatures were observed (41.0 degrees C+/-0.7
      to 76.7 degrees C+/-1.9), with coagulation diameter correlating logarithmically
      with radiofrequency duration and AUC (R2=0.85-0.95). The CEM43 demonstrated an
      extreme range of values (10(11)). CONCLUSION: The results of the study
      demonstrate a wide range of thermal sensitivity to RFA among commonly
      investigated tissues and tumor models, suggesting that further characterization
      of tissue-specific end points (ie, the duration and end temperature of ablation)
      is likely warranted. The AUC showed good correlation with ablation sizes, but the
      CEM43 proved unworkable given an extreme range of values for RFA.

PMID- 17494848
TI  - Right thyrocervical trunk bronchial artery collateral: source of type II Endoleak
      after endovascular repair of thoracic aortic aneurysm.
AB  - A patient with an enlarging thoracic aortic aneurysm (TAA) after endovascular
      repair showed a persistent endoleak on follow-up imaging at three and six months.
      He subsequently underwent angiography and transcatheter embolization of a right
      thyrocervical trunk bronchial collateral. Examination of potential anomalous or
      collateral thoracic pathways is mandatory when considering treatment of a Type II
      endoleak following endovascular TAA repair.

PMID- 17494849
TI  - Treatment of a large type II endoleak via extraperitoneal dissection and
      embolization of a collateral vessel using ethylene vinyl alcohol copolymer
      (Onyx).
AB  - Type II endoleak is defined as persistent blood flow and pressure within an
      aneurysmal sac after endovascular deployment of a stent graft from patent aortic
      branches. This paper describes the simultaneous deployment of an endoluminal
      graft, with limited extraperitoneal dissection of a collateral vessel and use of
      an ethylene vinyl alcohol copolymer, Onyx, to obliterate a large type II
      endoleak.

PMID- 17494850
TI  - Cutting balloon angioplasty in children with resistant renal artery stenosis.
AB  - Children with systemic hypertension resulting from a renovascular stenosis
      commonly have fibromuscular dysplasia and respond to percutaneous transluminal
      renal angioplasty (PTRA). There is a subset of children, however, with conditions
      that appear to be resistant to PTRA (eg, syndromic renal artery stenosis and
      arteritis). These patients are often treated surgically. The development of the
      cutting balloon may provide a minimally invasive alternative to surgery in these
      individuals. Associated adverse events may include recurrent stenosis, arterial
      occlusion with renal loss, and arterial rupture with extravasation and
      pseudoaneurysm formation. Some of these adverse events can be successfully
      treated with percutaneous interventional techniques. The authors present four
      cases of cutting balloon angioplasty performed at two large metropolitan
      children's hospitals in children with resistant renal artery stenosis.

PMID- 17494851
TI  - Dual use of an amplatzer device in the transcatheter embolization of a large high
      flow renal arteriovenous fistula.
AB  - Embolization procedures are now considered the first-line therapy in the
      treatment of renal arteriovenous fistulas (AVFs). However, a risk posed by the
      use of these minimally invasive techniques is the migration of occluding agents
      into the venous and pulmonary circulations. The risk is of particular importance
      for larger, high-flow fistulas. The authors describe a case in which an Amplatzer
      Vascular Plug (AVP) was opened upstream of a renal AVF in the dilated feeding
      artery and used as a filter and a buttress during coil embolization to prevent
      coil migration during the treatment of the large, high-flow renal AVF. It was
      then removed and used again as the final embolic device in the renal artery,
      performing a dual role in the closure of the renal AVF.

PMID- 17494852
TI  - Peripheral embolism due to bone entrapment of the popliteal artery after valgus
      osteotomy: a case report.
AB  - The authors report on a case of arterial embolism caused by bone entrapment of
      the popliteal artery due to a protrusion of a hydroxyl-apatite wedge. The wedge
      had been placed 4 years earlier during the course of a valgus osteotomy
      procedure. Thrombolytic therapy was performed, and the wedge was removed. Because
      causes for arterial embolism vary, the knowledge of its underlying mechanism is
      necessary to avoid recurring events. Bone entrapment after knee surgery is a
      differential diagnosis that should be taken into account, even years after
      surgery.

PMID- 17494853
TI  - Features influencing patient selection for fibroid treatment with magnetic
      resonance-guided focused ultrasound.
AB  - Of 333 women inquiring about minimally invasive image-guided treatments for
      fibroids, 209 (63%) were clinically eligible for magnetic resonance-guided
      focused ultrasound (MRgFUS) according to criteria specified by the Food and Drug
      Administration and our institution's institutional review board. One hundred
      three clinically eligible patients had pelvic MR imaging, and 26 (25%) were
      anatomically eligible for MRgFUS. A substantial proportion were anatomically
      ineligible for more than one reason, including too much fibroid volume (19%),
      presence of bowel in the ultrasound beam path (13%), and significant adenomyosis
      (12%). Overall, 14% of women inquiring about minimally invasive image-guided
      treatments for fibroids were eligible for MRgFUS, a percentage that increased
      when additional institutional review board restrictions were lifted.

PMID- 17494854
TI  - Spontaneous coronary artery dissection: noninvasive diagnosis with multidetector
      CT angiography.

PMID- 17494855
TI  - Acute endovascular repair of right subclavian arterial perforation from
      clavicular fracture after blunt trauma.

PMID- 17494856
TI  - Retrieval of a tilted recovery filter from a left-sided inferior vena cava with a
      loop snare.

PMID- 17494857
TI  - Bilateral persistent trigeminal arteries associated with bilateral carotid
      aneurysms.

PMID- 17494859
TI  - MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA
      resistance in patients with AML.
AB  - Overexpression of wild-type MN1 is a negative prognostic factor in patients with
      acute myeloid leukemia (AML) with normal cytogenetics. We evaluated whether MN1
      plays a functional role in leukemogenesis. We demonstrate using retroviral gene
      transfer and bone marrow (BM) transplantation that MN1 overexpression rapidly
      induces lethal AML in mice. Insertional mutagenesis and chromosomal instability
      were ruled out as secondary aberrations. MN1 increased resistance to all-trans
      retinoic acid (ATRA)-induced cell-cycle arrest and differentiation by more than
      3000-fold in vitro. The differentiation block could be released by fusion of a
      transcriptional activator (VP16) to MN1 without affecting the ability to
      immortalize BM cells, suggesting that MN1 blocks differentiation by
      transcriptional repression. We then evaluated whether MN1 expression levels in
      patients with AML (excluding M3-AML) correlated with resistance to ATRA treatment
      in elderly patients uniformly treated within treatment protocol AMLHD98-B.
      Strikingly, patients with low MN1 expression who received ATRA had a
      significantly prolonged event-free (P = .008) and overall (P = .04) survival
      compared with patients with either low MN1 expression and no ATRA, or high MN1
      expression with or without ATRA. MN1 is a unique oncogene in hematopoiesis that
      both promotes proliferation/self-renewal and blocks differentiation, and may
      become useful as a predictive marker in AML treatment.

PMID- 17494858
TI  - Distinct patterns of mutations occurring in de novo AML versus AML arising in the
      setting of severe congenital neutropenia.
AB  - Severe congenital neutropenia (SCN) is an inborn disorder of granulopoiesis. Like
      most other bone marrow failure syndromes, it is associated with a marked
      propensity to transform into a myelodysplastic syndrome (MDS) or acute leukemia,
      with a cumulative rate of transformation to MDS/leukemia that exceeds 20%. The
      genetic (and/or epigenetic) changes that contribute to malignant transformation
      in SCN are largely unknown. In this study, we performed mutational profiling of
      14 genes previously implicated in leukemogenesis using 14 MDS/leukemia samples
      from patients with SCN. We used high-throughput exon-based resequencing of whole
      genome-amplified genomic DNA with a semiautomated method to detect mutations. The
      sensitivity and specificity of the sequencing pipeline was validated by
      determining the frequency of mutations in these 14 genes using 188 de novo AML
      samples. As expected, mutations of tyrosine kinase genes (FLT3, KIT, and JAK2)
      were common in de novo AML, with a cumulative frequency of 30%. In contrast, no
      mutations in these genes were detected in the SCN samples; instead, mutations of
      CSF3R, encoding the G-CSF receptor, were common. These data support the
      hypothesis that mutations of CSF3R may provide the "activated tyrosine kinase
      signal" that is thought to be important for leukemogenesis.

PMID- 17494860
TI  - Myeloma bone disease and proteasome inhibition therapies.
AB  - Bone disease is one of the most debilitating manifestations of multiple myeloma.
      A complex interdependence exists between myeloma bone disease and tumor growth,
      creating a vicious circle of extensive bone destruction and myeloma progression.
      Proteasome inhibitors have recently been shown to promote bone formation in vitro
      and in vivo. Preclinical studies have demonstrated that proteasome inhibitors,
      including bortezomib, which is the first-in-class such agent, stimulate
      osteoblast differentiation while inhibiting osteoclast formation and bone
      resorption. Clinical studies are confirming these observations. Bortezomib
      counteracts the abnormal balance of osteoclast regulators (receptor activator of
      nuclear factor-kappaB ligand and osteoprotegerin), leading to osteoclast
      inhibition and decreased bone destruction, as measured by a reduction in markers
      of bone resorption. In addition, bortezomib stimulates osteoblast function,
      possibly through the reduction of dickkopf-1, leading to increased bone
      formation, as indicated by the elevation in bone-specific alkaline phosphatase
      and osteocalcin. The effect of bortezomib on bone disease is thought to be direct
      and not only a consequence of the agent's antimyeloma properties, making it an
      attractive agent for further investigation, as it may combine potent antimyeloma
      activity with beneficial effects on bone. However, the clinical implication of
      these effects requires prospective studies with specific clinical end points.

PMID- 17494861
TI  - Determination of adenosine effects and adenosine receptors in murine corpus
      cavernosum.
AB  - This study tested the hypothesis that adenosine, in murine corpora cavernosa,
      produces direct relaxation of smooth muscle cells and inhibition of contractile
      responses mediated by sympathetic nerve stimulation. Penes were excised from
      anesthetized male C57BL/6 mice, dissected, and cavernosal strips were mounted to
      record isometric force. Adenosine, 2-chloroadenosine (stable analog of
      adenosine), and 2-phenylaminoadenosine (CV1808) (A2(A)/A2(B) agonist) produced
      concentration-dependent relaxations of phenylephrine-contracted tissues.
      Relaxation to 2-chloroadenosine was inhibited, in a concentration-dependent
      manner, by 2-(2-furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5
      c]pyrimidin-5-amine (SCH58261; A2(A) antagonist; 10(-9)-10(-6) M) and N-(4
      acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8
      yl)phenoxy]acetamida (MRS1706; A2(B) antagonist; 10(-8)-10(-6) M). The
      combination of both antagonists abrogated 2-chloroadenosine-induced relaxation.
      Electrical field stimulation (EFS; 1-32 Hz) of adrenergic nerves produced
      frequency-dependent contractions that were inhibited by compounds that increase
      adenosine levels, such as 5'-iodotubercidin (adenosine kinase inhibitor), erythro
      9-(2-hydroxy-3-nonyl)adenine (adenosine deaminase inhibitor), and dipyridamole
      (inhibitor of adenosine transport). The adenosine A1 receptor agonist N(6)
      cyclopentyladenosine (C8031) right-shifted contractile responses to EFS, with a
      significant inhibitory effect at 10(-6) M. Blockade of adenosine A1 receptors
      with 8-cyclopentyl-1,3-dipropylxanthine (C101) (10(-7) M) enhanced contractile
      responses to EFS and eliminated the inhibitory effects of 5'-iodotubercidin.
      Dipyridamole and 5'-iodotubercidin had no effect on adenosine-mediated
      relaxation. In summary, adenosine directly relaxes cavernosal smooth muscle
      cells, by the activation of A2(A)/A2(B) receptor subtypes. In addition, adenosine
      negatively modulates sympathetic neurotransmission, by A1 receptor subtype
      activation, in murine corpora cavernosa. Adenosine may subserve dual roles in
      modulating the physiological mechanisms of erection in mice.

PMID- 17494862
TI  - Ciglitazone, a peroxisome proliferator-activated receptor gamma inducer,
      ameliorates renal preglomerular production and activity of angiotensin II and
      thromboxane A2 in glycerol-induced acute renal failure.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear
      transcription factor, modulates vascular responses to angiotensin II (AII) or
      thromboxane A(2) (TxA(2)) via regulation of their gene/receptor. Increased
      vasoconstriction and deteriorating renal function in glycerol-induced acute renal
      failure (ARF) may be attributed to down-regulation of PPARgamma. In this study,
      we investigated the effect of ciglitazone (CG), a PPARgamma inducer, on AII and
      TxA(2) production and activity in glycerol-induced ARF. Vascular responses to AII
      or 9,11-dideoxy-11alpha,9alpha-epoxymethano prostaglandin F(2alpha) (U46619), a
      TxA(2) mimetic, were determined in preglomerular vessels following induction of
      ARF with glycerol. Renal damage and function were assessed in CG-treated (9
      nmol/kg for 21 days) rats. PPARgamma protein expression and activity, which were
      significantly lower in ARF rats, were enhanced by CG (26 and 30%). CG also
      increased PPARgamma mRNA by 67 +/- 6%, which was reduced in ARF. In ARF, there
      was significant tubular necrosis and apoptosis, a 5-fold increase in proteinuria
      and a 2-fold enhancement in vasoconstriction to AII and U46619. CG reduced
      proteinuria (49 +/- 3%), enhanced Na(+) (124 +/- 35%) and creatinine excretion
      (92 +/- 25%), markedly diminished tubular necrosis, and reduced ARF-induced
      increase in AII (40 +/- 3%) and TxA(2) (39 +/- 2%) production, the attending
      increase in vasoconstriction to AII (36 +/- 2%) and U46619 (50 +/- 11%), and the
      increase in angiotensin receptor-1 (AT(1)) (23 +/- 3%) or thromboxane
      prostaglandin (TP) receptor (13 +/- 1%). CG reduced free radical generation by 55
      +/- 14% while elevating nitrite excretion (65 +/- 13%). Our results suggest that
      enhanced activity of AII and TxA(2), increased AT(1) or TP receptor expression,
      and renal injury in glycerol-induced ARF are consequent to down-regulation of
      PPARgamma gene. CG ameliorated glycerol-induced effects through maintaining
      PPARgamma gene.

PMID- 17494863
TI  - Mechanisms responsible for the enhanced antinociceptive effects of micro-opioid
      receptor agonists in the rostral ventromedial medulla of male rats with
      persistent inflammatory pain.
AB  - This study investigated three possible mechanisms by which the antinociceptive
      effects of the mu-opioid receptor (MOR) agonist [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]
      enkephalin (DAMGO) and the delta-opioid receptor (DOR) agonist [d-Ala(2),Glu(4)]
      deltorphin (deltorphin II) (DELT), microinjected into the rostral ventromedial
      medulla (RVM), are enhanced in rats with persistent inflammatory injury.
      Radioligand binding determined that neither the B(max) nor the K(d) values of
      [(3)H]DAMGO differed in RVM membranes from rats that received an intraplantar
      injection of saline or complete Freund's adjuvant (CFA) in one hindpaw 4 h, 4
      days, or 2 weeks earlier. Likewise, neither the EC(50) nor the E(max) value for
      DAMGO-induced stimulation of guanosine 5'-O-(3-[(35)S]thio)triphosphate
      ([(35)S]GTPgammaS) binding differed in the RVM of saline- or CFA-treated rats at
      any time point. Microinjection of fixed dose combinations of DAMGO and DELT in
      the RVM of naive rats indicated that these agonists interact synergistically to
      produce antinociception when DAMGO is present in equal or greater amounts than
      DELT and, additively, when DELT is the predominant component. Thus, unlike the
      periphery or spinal cord, potentiation of MOR-mediated antinociception does not
      entail an increase in MOR number, affinity, or coupling. Rather, the data are
      concordant with our proposal that potentiation results from a synergistic
      interaction of exogenous MOR agonist with DOR-preferring enkephalins whose levels
      are increased in CFA-treated rats (J Neurosci 21:2536-2545, 2001). Virtually no
      specific [(3)H]DELT binding nor stimulation of [(35)S]GTPgammaS binding by DELT
      was obtained in RVM membranes from CFA- or saline-treated rats at any time point.
      The mechanisms responsible for the potentiation of DELT-mediated antinociception
      remain to be elucidated.

PMID- 17494864
TI  - The effect of recombinant human erythropoietin on neurovasculature repair after
      focal ischemic stroke in neonatal rats.
AB  - Cerebral ischemia disrupts the neurovascular unit, involving death of neuronal,
      glial, and endothelial cells (ECs) in the core and penumbra regions. Whereas the
      neuroprotective effect of recombinant human erythropoietin (rhEPO) has been
      widely investigated, its effects on ECs remain elusive. We now report the effects
      of rhEPO treatment on EC death and neurovasculature repair following a focal
      ischemic stroke in postnatal day 7 neonatal rats. rhEPO (5000 U/kg i.p.) was
      administered 60 min after ischemia and for the next 3 days. Western blot analysis
      revealed increased expression of neurovascular remodeling proteins, including Tie
      1, angiopoietin-2, and basic fibroblast growth factor in rhEPO-treated pups.
      rhEPO treatment significantly reduced EC death in the ischemic penumbra region 12
      to 72 h after ischemia examined by immunostaining of terminal deoxynucleotidyl
      transferase dUTP nick-end labeling and EC marker glucose transporter-1 (GLUT-1).
      Treatment with rhEPO increased proliferation of ECs and neuronal cells, revealed
      by costaining of 5-bromo-2'-deoxyuridine with GLUT-1 or with the neuronal marker
      protein (NeuN) 7 to 21 days after stroke. Specifically, rhEPO increased number of
      NeuN-positive cells in close proximity to proliferating microvessels. These
      results suggest for the first time that, in addition to its protection on neural
      cells, EPO protects ECs and promotes the neurovascular unit repair, which may
      contribute to its therapeutic benefits after neonatal ischemic stroke.

PMID- 17494865
TI  - Distinct Ca2+ requirement for NO production between proteinase-activated receptor
      1 and 4 (PAR1 and PAR4) in vascular endothelial cells.
AB  - Proteinase-activated receptors 1 and 4 (PAR(1) and PAR(4)) are the major
      receptors mediating thrombin-induced NO production in endothelial cells. The
      intracellular signaling following their activation still remains to be
      elucidated. The present study provides the first evidence for the distinct Ca(2+)
      requirement for the NO production between PAR(1) and PAR(4). The activation of
      PAR(1) by the activating peptide (PAR(1)-AP) elevated cytosolic Ca(2+)
      concentrations ([Ca(2+)](i)) and activated NO production in porcine aortic and
      human umbilical vein endothelial cells, whereas it had little effect on bovine
      aortic endothelial cells. PAR(4) activation by PAR(4)-AP consistently induced NO
      production without an appreciable [Ca(2+)](i) elevation in three types of
      endothelial cells. The PAR(1)-mediated NO production was significantly inhibited
      by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), whereas the
      PAR(4)-mediated NO production was resistant. NO production following the PAR(1)
      and PAR(4) activation was significantly inhibited by pertussis toxin, but it was
      resistant to a Galpha(q/11) inhibitor, YM254890 [(1R)-1
      [(3S,6S,9S,12S,18R,21S,22R)-21-acetamido-18-benzyl-3-[(1R)-1-methoxyethyl]
      4,9,10,12,16,22-hexamethyl-15-methylene-2,5,8,11,14,17,20-heptaoxo-1,19-dioxa
      4,7,10,13,16-pentaazacyclodocosan-6-yl]-2-methylpropyl rel-(2S,3R)-2-acetamido-3
      hydroxy-4-methylpentanoate]. However, YM254890 abrogated the PAR(1)-mediated
      Ca(2+) signal. PAR(4)-mediated NO production was substantially inhibited by the
      inhibitors of phosphotidylinositol-3 kinase (PI3K) and Akt, as well as by the
      dominant negative mutant of Akt. The PAR(1)-mediated NO production was relatively
      resistant to inhibitors of PI3K. An immunoblot analysis revealed a transient
      increase in the phosphorylation of Akt and endothelial NO synthase following the
      PAR(4) stimulation. In conclusion, PAR(1) and PAR(4) engage distinct signal
      transduction mechanisms to activate NO production in vascular endothelial cells.
      PAR(4) preferably activates Galpha(i/o) and induced NO production in a manner
      mostly independent of Ca(2+) but dependent on the PI3K/Akt pathway, whereas
      PAR(1) activates both the Ca(2+)-dependent and -independent mechanisms.

PMID- 17494866
TI  - Depletion of the nucleolar protein nucleostemin causes G1 cell cycle arrest via
      the p53 pathway.
AB  - Nucleostemin (NS) is a nucleolar protein expressed in adult and embryo-derived
      stem cells, transformed cell lines, and tumors. NS decreases when proliferating
      cells exit the cell cycle, but it is unknown how NS is controlled, and how it
      participates in cell growth regulation. Here, we show that NS is down-regulated
      by the tumor suppressor p14(ARF) and that NS knockdown elevates the level of
      tumor suppressor p53. NS knockdown led to G1 cell cycle arrest in p53-positive
      cells but not in cells in which p53 was genetically deficient or depleted by
      small interfering RNA knockdown. These results demonstrate that, in the cells
      investigated, the level of NS is regulated by p14(ARF) and the control of the
      G1/S transition by NS operates in a p53-dependent manner.

PMID- 17494867
TI  - Exogenous MAL reroutes selected hepatic apical proteins into the direct pathway
      in WIF-B cells.
AB  - Unlike simple epithelial cells that directly target newly synthesized
      glycophosphatidylinositol (GPI)-anchored and single transmembrane domain (TMD)
      proteins from the trans-Golgi network to the apical membrane, hepatocytes use an
      indirect pathway: proteins are delivered to the basolateral domain and then
      selectively internalized and transcytosed to the apical plasma membrane. Myelin
      and lymphocyte protein (MAL) and MAL2 have been identified as regulators of
      direct and indirect apical delivery, respectively. Hepatocytes lack endogenous
      MAL consistent with the absence of direct apical targeting. Does MAL expression
      reroute hepatic apical residents into the direct pathway? We found that MAL
      expression in WIF-B cells induced the formation of cholesterol and
      glycosphingolipid-enriched Golgi domains that contained GPI-anchored and single
      TMD apical proteins; polymeric IgA receptor (pIgA-R), polytopic apical, and
      basolateral resident distributions were excluded. Basolateral delivery of newly
      synthesized apical residents was decreased in MAL-expressing cells concomitant
      with increased apical delivery; pIgA-R and basolateral resident delivery was
      unchanged. These data suggest that MAL rerouted selected hepatic apical proteins
      into the direct pathway.

PMID- 17494868
TI  - PI4P promotes the recruitment of the GGA adaptor proteins to the trans-Golgi
      network and regulates their recognition of the ubiquitin sorting signal.
AB  - Phosphatidylinositol 4 phosphate (PI4P) is highly enriched in the trans-Golgi
      network (TGN). Here we establish that PI4P is a key regulator of the recruitment
      of the GGA clathrin adaptor proteins to the TGN and that PI4P has a novel role in
      promoting their recognition of the ubiquitin (Ub) sorting signal. Knockdown of
      PI4KIIalpha by RNA interference (RNAi), which depletes the TGN's PI4P, impaired
      the recruitment of the GGAs to the TGN. GGAs bind PI4P primarily through their
      GAT domain, in a region called C-GAT, which also binds Ub but not Arf1. We
      identified two basic residues in the GAT domain that are essential for PI4P
      binding in vitro and for the recruitment of GGAs to the TGN in vivo. Unlike wild
      type GGA, GGA with mutated GATs failed to rescue the abnormal TGN phenotype of
      the GGA RNAi-depleted cells. These residues partially overlap with those that
      bind Ub, and PI4P increased the affinity of the GAT domain for Ub. Because the
      recruitment of clathrin adaptors and their cargoes to the TGN is mediated through
      a web of low-affinity interactions, our results show that the dual roles of PI4P
      can promote specific GGA targeting and cargo recognition at the TGN.

PMID- 17494869
TI  - A novel AAK1 splice variant functions at multiple steps of the endocytic pathway.
AB  - Phosphorylation is a critical step in regulating receptor transport through the
      endocytic pathway. AAK1 is a serine/threonine kinase that is thought to
      coordinate the recruitment of AP-2 to receptors containing tyrosine-based
      internalization motifs by phosphorylating the micro2 subunit. Here we have
      identified a long form of AAK1 (AAK1L) that contains an extended C-terminus that
      encodes an additional clathrin-binding domain (CBD2) consisting of multiple low
      affinity interaction motifs. Protein interaction studies demonstrate that AAK1L
      CBD2 directly binds clathrin. However, in vitro kinase assays reveal little
      difference between AAK1 isoforms in their basal or clathrin-stimulated kinase
      activity toward the AP-2 micro2 subunit. However, overexpression of AAK1L CBD2
      impairs transferrin endocytosis, confirming an endocytic role for AAK1.
      Surprisingly, CBD2 overexpression or AAK1 depletion by RNA interference
      significantly impairs transferrin recycling from the early/sorting endosome.
      These observations suggest that AAK1 functions at multiple steps of the endosomal
      pathway by regulating transferrin internalization and its rapid recycling back to
      the plasma membrane from early/sorting endosome.

PMID- 17494870
TI  - Anchoring of protein kinase A-regulatory subunit IIalpha to subapically
      positioned centrosomes mediates apical bile canalicular lumen development in
      response to oncostatin M but not cAMP.
AB  - Oncostatin M and cAMP signaling stimulate apical surface-directed membrane
      trafficking and apical lumen development in hepatocytes, both in a protein kinase
      A (PKA)-dependent manner. Here, we show that oncostatin M, but not cAMP, promotes
      the A-kinase anchoring protein (AKAP)-dependent anchoring of the PKA regulatory
      subunit (R)IIalpha to subapical centrosomes and that this requires extracellular
      signal-regulated kinase 2 activation. Stable expression of the RII-displacing
      peptide AKAP-IS, but not a scrambled peptide, inhibits the association of
      RIIalpha with centrosomal AKAPs and results in the repositioning of the
      centrosome from a subapical to a perinuclear location. Concomitantly, common
      endosomes, but not apical recycling endosomes, are repositioned from a subapical
      to a perinuclear location, without significant effects on constitutive or
      oncostatin M-stimulated basolateral-to-apical transcytosis. Importantly, however,
      the expression of the AKAP-IS peptide completely blocks oncostatin M-, but not
      cAMP-stimulated apical lumen development. Together, the data suggest that
      centrosomal anchoring of RIIalpha and the interrelated subapical positioning of
      these centrosomes is required for oncostatin M-, but not cAMP-mediated, bile
      canalicular lumen development in a manner that is uncoupled from oncostatin M
      stimulated apical lumen-directed membrane trafficking. The results also imply
      that multiple PKA-mediated signaling pathways control apical lumen development
      and that subapical centrosome positioning is important in some of these pathways.

PMID- 17494871
TI  - Nudel modulates kinetochore association and function of cytoplasmic dynein in M
      phase.
AB  - The microtubule-based motor cytoplasmic dynein/dynactin is a force generator at
      the kinetochore. It also transports proteins away from kinetochores to spindle
      poles. Regulation of such diverse functions, however, is poorly understood. We
      have previously shown that Nudel is critical for dynein-mediated protein
      transport, whereas mitosin, a kinetochore protein that binds Nudel, is involved
      in retention of kinetochore dynein/dynactin against microtubule-dependent
      stripping. Here we demonstrate that Nudel is required for robust localization of
      dynein/dynactin at the kinetochore. It localizes to kinetochores after nuclear
      envelope breakdown, depending mostly ( approximately 78%) on mitosin and slightly
      on dynein/dynactin. Depletion of Nudel by RNA interference (RNAi) or
      overexpression of its mutant incapable of binding either Lis1 or dynein heavy
      chain abolishes the kinetochore protein transport and mitotic progression.
      Similar to mitosin RNAi, Nudel RNAi also leads to increased stripping of
      kinetochore dynein/dynactin in the presence of microtubules. Taking together, our
      results suggest a dual role of kinetochore Nudel: it activates dynein-mediated
      protein transport and, when interacting with both mitosin and dynein, stabilizes
      kinetochore dynein/dynactin against microtubule-dependent stripping to facilitate
      the force generation function of the motor.

PMID- 17494872
TI  - Recycling endosomes of polarized epithelial cells actively sort apical and
      basolateral cargos into separate subdomains.
AB  - The plasma membranes of epithelial cells plasma membranes contain distinct apical
      and basolateral domains that are critical for their polarized functions. However,
      both domains are continuously internalized, with proteins and lipids from each
      intermixing in supranuclear recycling endosomes (REs). To maintain polarity, REs
      must faithfully recycle membrane proteins back to the correct plasma membrane
      domains. We examined sorting within REs and found that apical and basolateral
      proteins were laterally segregated into subdomains of individual REs. Subdomains
      were absent in unpolarized cells and developed along with polarization.
      Subdomains were formed by an active sorting process within REs, which precedes
      the formation of AP-1B-dependent basolateral transport vesicles. Both the
      formation of subdomains and the fidelity of basolateral trafficking were
      dependent on PI3 kinase activity. This suggests that subdomain and transport
      vesicle formation occur as separate sorting steps and that both processes may
      contribute to sorting fidelity.

PMID- 17494874
TI  - Evidence for the use of hearing assistive technology by adults: the role of the
      FM system.
AB  - Hearing assistive technologies include listening, alerting, and/or signaling
      devices that use auditory, visual, and/or tactile modalities to augment
      communication and/or facilitate awareness of environmental sounds. The importance
      of hearing assistive technologies in the management of adults with hearing loss
      was recently acknowledged in an evidence-based clinical practice guideline
      developed by the American Academy of Audiology. Most currently available evidence
      for hearing assistive technology use by adults focuses on frequency-modulated
      (FM) technology. Previous research is reviewed that demonstrates the efficacy of
      FM devices for adults in terms of laboratory measures of speech understanding in
      noise. Also reviewed are the outcomes from field trials of FM use by community
      dwelling adults, which, to date, have been disappointing. Few to no individuals,
      in previous studies, elected to use FM devices at the end of the trial periods.
      Data are presented from a 1-group pretest-posttest study examining the role of
      extensive counseling, coaching, and instruction on FM use by adults. In addition,
      the potential influence of the cost of devices to the individual was eliminated
      by conducting the study with veterans who were eligible to receive FM systems
      through the Veterans Affairs National Hearing Aid Program. Positive outcomes were
      obtained at the end of a 6-week trial period and were found to remain 1 year
      after study completion. Implications for increasing the evidence base for the use
      of FM devices by adults are discussed.

PMID- 17494873
TI  - Adult aural rehabilitation: what is it and does it work?
AB  - Adult aural rehabilitation is here defined holistically as the reduction of
      hearing-loss-induced deficits of function, activity, participation, and quality
      of life through a combination of sensory management, instruction, perceptual
      training, and counseling. There is a tendency for audiologists to focus on
      sensory management, aural rehabilitation being seen as something done by someone
      else after the provision of hearing aids or cochlear implants. Effective sensory
      management may, by itself, lead to improved activity, participation, and quality
      of life, but there is no guarantee that these outcomes will be automatic or
      optimal. In fact, there is often a disconnect between clinical measures of
      assisted auditory function and self-assessed benefit. Costs associated with a
      holistic approach can be minimized by bundling as many as possible into the cost
      of hearing devices, by taking advantage of computer-based perceptual training,
      and by capitalizing on the benefits of group counseling.

PMID- 17494875
TI  - An internet survey of individuals with hearing loss regarding assistive listening
      devices.
AB  - An Internet survey of individuals with hearing loss was conducted to determine
      their use of assistive listening devices for face-to-face conversation and, while
      part of an audience, their satisfaction with assistive listening devices, their
      interest in the concept of a universal assistive listening device receiver, and
      their interest in receiving audiologic information and services through the
      Internet. The 423 respondents who used assistive listening devices found them to
      be of significant benefit across a range of listening situations. Most
      respondents were open to the idea of purchasing a personal device that could work
      both with hearing aids and a range of transmission media. Probably because of the
      sampling bias inherent in an Internet survey, respondents were inclined to choose
      Internet-based and peer-based sources of information, and made many suggestions
      for both improving assistive listening devices and for improving information
      available about them by using the Internet.

PMID- 17494876
TI  - Technologic advances in aural rehabilitation: applications and innovative methods
      of service delivery.
AB  - The level of interest in aural rehabilitation has increased recently, both in
      clinical use and in research presentations and publications. Advances in aural
      rehabilitation have seen previous techniques such as speech tracking and analytic
      auditory training reappear in computerized forms. These new delivery methods
      allow for a consistent, cost-effective, and convenient training program. Several
      computerized aural rehabilitation programs for hearing aid wearers and cochlear
      implant recipients have recently been developed and were reported on at the 2006
      State of the Science Conference of the Rehabilitation Engineering Research Center
      on Hearing Enhancement at Gallaudet University. This article reviews these
      programs and outlines the similarities and differences in their design. Another
      promising area of aural rehabilitation research is the use of pharmaceuticals in
      the rehabilitation process. The results from a study of the effect of d
      amphetamine in conjunction with intensive aural rehabilitation with cochlear
      implant patients are also described.

PMID- 17494877
TI  - Issues associated with the measurement of psychosocial benefits of group
      audiologic rehabilitation programs.
AB  - The purpose of this review is to describe the psychosocial effects of hearing
      loss, review the literature that has attempted to measure the psychosocial
      benefits of group audiologic rehabilitation programs, and offer suggestions for
      the design of future studies. The psychosocial aspects of hearing loss are
      multidimensional and may include the emotional, cognitive, interpersonal,
      behavioral, and physical responses to hearing loss. As a result of the stigma of
      hearing loss, individuals may isolate themselves, avoid social interactions,
      and/or bluff their way through communication breakdowns. Participation in group
      audiologic rehabilitation programs is a straightforward way to deal with the
      stigma and the loss of social identity associated with hearing loss, and these
      groups are an ideal forum for teaching communication strategies. Yet, the
      literature on the efficacy of group audiologic rehabilitation has produced
      equivocal results. Several factors may have contributed to the lack of
      psychosocial benefits reported in the literature, including the theoretical
      framework upon which the program was designed, the actual class content, the
      effectiveness of the outcome measures, and the demographic characteristics of the
      participants in the programs. Future research should determine (1) if the
      theoretical framework and/or the content covered in group audiologic
      rehabilitation programs influences the psychosocial outcomes, (2) if instructor
      training influences psychosocial outcomes, (3) the ideal test battery to assess
      the psychosocial benefits of group audiologic rehabilitation programs, (4) the
      participant demographic and personality characteristics that influence
      psychosocial outcomes, and (5) whether experienced hearing aid users have
      different hearing-loss related psychosocial needs than new hearing aid users.

PMID- 17494878
TI  - A peer mentor training program for aural rehabilitation.
AB  - This article describes a new training program at Gallaudet University that aims
      to prepare peer mentors to work under the supervision of hearing-health
      professionals in the area of aural rehabilitation (AR). The paucity of AR
      programs for consumers with hearing loss in the United States has been
      documented. The peer mentor training program is an attempt to harness the
      energies, skills, and knowledge of people with hearing loss; to expand them
      through a program of academic and experiential learning; and to put them to work
      in audiologic practices and other hearing-health care settings in order to
      improve the quality and quantity of AR available to consumers. A peer mentor
      training curriculum is described, and the current status of the educational
      program is reported. Initial anecdotal evidence suggests that the program has the
      potential to contribute to the development of a more comprehensive model of AR
      service delivery.

PMID- 17494879
TI  - Renal replacement therapy in the developing world: are we on the right track, or
      should there be a new paradigm?

PMID- 17494880
TI  - Is proteinuria reduction by angiotensin-converting enzyme inhibition enough to
      prove its role in renal protection in IgA nephropathy?

PMID- 17494881
TI  - A randomized, controlled trial of steroids and cyclophosphamide in adults with
      nephrotic syndrome caused by idiopathic membranous nephropathy.
AB  - Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic
      syndrome in adults. Universal consensus regarding the need for and the modality
      of therapy has not been formed because of a lack of controlled trials of
      sufficient size, quality, and duration. This study compared the effect of a 6-mo
      course of alternating prednisolone and cyclophosphamide with supportive treatment
      in adults with nephrotic syndrome caused by IMN on doubling of serum creatinine,
      development of ESRD, and quality of life in a randomized, controlled trial.
      Patients were followed up for 10 yr. Data were analyzed on an intention-to-treat
      basis. A total of 93 patients completed the study. Of the 47 patients who
      received the experimental protocol, 34 achieved remission (15 complete and 19
      partial), compared with 16 (five complete, 11 partial) of 46 in the control group
      (P < 0.0001). The 10-yr dialysis-free survival was 89 and 65% (P = 0.016), and
      the likelihood of survival without death, dialysis, and doubling of serum
      creatinine were 79 and 44% (P = 0.0006) in the two groups. Treated patients
      exhibited significantly lower prevalence of edema, hypertension, hypoalbuminemia,
      hyperlipidemia that required therapy, angiotensin-converting enzyme
      inhibitor/angiotensin II receptor blocker use, and better quality of life on
      follow-up. The incidence of infections was similar in the two groups. In
      conclusion, untreated IMN with nephrotic syndrome is associated with a high risk
      for deterioration of renal function. A 6-mo regimen of cyclophosphamide and
      steroids induces remissions in a high proportion, arrests progression of renal
      insufficiency, and improves quality of life.

PMID- 17494882
TI  - How fibroblast growth factor 23 works.
AB  - There is a discontinuum of hereditary and acquired disorders of phosphate
      homeostasis that are caused by either high or low circulating levels of the novel
      phosphaturic hormone fibroblastic growth factor 23 (FGF23). Disorders that are
      caused by high circulating levels of FGF23 are characterized by hypophosphatemia,
      decreased production of 1,25-dihydroxyvitamin D, and rickets/osteomalacia. On the
      other end of the spectrum are disorders that are caused by low circulating levels
      of FGF23, which are characterized by hyperphosphatemia, elevated production of
      1,25-dihydroxyvitamin D, soft tissue calcifications, and hyperostosis. Knowledge
      of the genetic basis of these hereditary disorders of phosphate homeostasis and
      studies of their mouse homologues have uncovered a bone-kidney axis and new
      systems biology that govern bone mineralization, vitamin D metabolism,
      parathyroid gland function, and renal phosphate handling. Further understanding
      of this primary phosphate homeostatic pathway has the potential to have a
      significant impact on the diagnosis and treatment of disorders of bone and
      mineral metabolism.

PMID- 17494883
TI  - Evidence for the role of reactive nitrogen species in polymicrobial sepsis
      induced renal peritubular capillary dysfunction and tubular injury.
AB  - Acute kidney injury (AKI) remains a frequent and serious complication of human
      sepsis that contributes significantly to mortality. For better understanding of
      the development of AKI during sepsis, the cecal ligation and puncture (CLP)
      murine model of sepsis was studied using intravital video microscopy (IVVM) of
      the kidney. IVVM with FITC-dextran was used to determine the percentage of
      capillaries with continuous, intermittent or no flow at 0 (sham), 10, 16, and 22
      h after CLP. There was a dramatic fall in capillary perfusion as early as 10 h
      after CLP that persisted through 22 h. The percentage of vessels with continuous
      flow at 16 h decreased from 73 +/- 2% in shams to 16 +/- 2% (P < 0.05), whereas
      the percentage of vessels with no flow increased from 4 +/- 1% in shams to 42 +/-
      2% (P < 0.05). The capillary perfusion defect preceded the rise in serum
      creatinine. IVVM with dihydrorhodamine-123 was used to quantify in real time
      reactive nitrogen species (RNS) generation by renal tubules, and the inducible
      nitric oxide synthase inhibitor L-iminoethyl-lysine (mg/kg) was used to examine
      the role of inducible nitric oxide synthase inhibitor on capillary dysfunction
      and RNS generation. Tubular generation of RNS was significantly elevated at 10 h
      after CLP and was associated with tubules that were bordered by capillaries with
      reduced perfusion. L-iminoethyl-lysine significantly reversed the capillary
      perfusion defect, blocked RNS generation, and reduced AKI. These data show that
      capillary dysfunction and RNS generation contribute to tubular injury and suggest
      that RNS should be considered a potential therapeutic target in the treatment of
      sepsis-induced AKI.

PMID- 17494884
TI  - Survival among patients with kidney failure in Jalisco, Mexico.
AB  - ESRD is a serious public health problem in the state of Jalisco, Mexico. This
      study evaluated mortality in poor patients who initiated dialysis at the Jalisco
      Health Secretariat, compared with Hispanic patients without medical insurance who
      initiated dialysis in the United States. All patients who received a diagnosis
      with ESRD between February 1 and December 31, 2003, were studied prospectively at
      a single institution that provides care to the poor of Jalisco. Data from an
      American national dialysis registry and Cox proportional hazards models were used
      to compare the adjusted survival among Jalisco patients with that of a
      contemporaneous group of incident Hispanic patients who did not have Medicare or
      private insurance cover and who initiated peritoneal dialysis in the United
      States. Of 274 consecutive patients who presented with a clinical diagnosis of
      ESRD in Jalisco, mean estimated GFR at dialysis initiation was very low (3.9 +/-
      2.4 ml/min per 1.73 m(2)), and <10% were previously known to a nephrologist. Of
      the 274 patients, 102 (37.2%) did not initiate dialysis therapy, 71 (69.6%) of
      whom died during follow-up. The majority (n = 49) of such deaths occurred in
      hospital before dialysis initiation. Of 172 patients who initiated dialysis, 36
      (20.9%) died within the first 90 d of renal replacement therapy. An additional 31
      (18.0%) patients died during a median follow-up of 186 d. When all 274 Jalisco
      patients who presented with ESRD were considered, survival was 49.6% at the end
      of follow-up. Unadjusted mortality rates among those who survived at least 90 d
      after dialysis initiation were 19.2 (95% confidence interval [CI] 13.5 to 27.3)
      and 5.9 (95% CI 4.6 to 7.7) per 100 patient-years in Jalisco and American
      patients, respectively. After adjustment, the risk for death remained nearly
      three-fold higher in Jalisco patients (hazard ratio 2.7; 95% CI 1.5 to 4.7). Poor
      patients with kidney failure in Jalisco have very advanced disease at the time of
      first nephrologic contact and have exceedingly high rates of mortality after
      dialysis initiation. Our findings demonstrate a tremendous opportunity to reduce
      morbidity and mortality from kidney disease in Jalisco and perhaps other regions
      of Mexico.

PMID- 17494885
TI  - Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized
      controlled study of benazepril and losartan in chronic renal insufficiency.
AB  - The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to
      determine whether titration of benazepril or losartan to optimal antiproteinuric
      doses would safely improve the renal outcome in chronic renal insufficiency. A
      total of 360 patients who did not have diabetes and had proteinuria and chronic
      renal insufficiency were randomly assigned to four groups. Patients received open
      label treatment with a conventional dosage of benazepril (10 mg/d), individual
      uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage
      of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d;
      range 50 to 200). Uptitration was performed to optimal antiproteinuric and
      tolerated dosages, and then these dosages were maintained. Median follow-up was
      3.7 yr. The primary end point was time to the composite of a doubling of the
      serum creatinine, ESRD, or death. Secondary end points included changes in the
      level of proteinuria and the rate of progression of renal disease. Compared with
      the conventional dosages, optimal antiproteinuric dosages of benazepril and
      losartan that were achieved through uptitration were associated with a 51 and 53%
      reduction in the risk for the primary end point (P = 0.028 and 0.022,
      respectively). Optimal antiproteinuric dosages of benazepril and losartan, at
      comparable BP control, achieved a greater reduction in both proteinuria and the
      rate of decline in renal function compared with their conventional dosages. There
      was no significant difference for the overall incidence of major adverse events
      between groups that were given conventional and optimal dosages in both arms. It
      is concluded that uptitration of benazepril or losartan against proteinuria
      conferred further benefit on renal outcome in patients who did not have diabetes
      and had proteinuria and renal insufficiency.

PMID- 17494886
TI  - Carotid intima media thickness predicts cardiovascular diseases in Chinese
      predialysis patients with chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) have a high risk for cardiovascular
      disease. Ultrasound measurements of the intima media thickness (IMT) in the
      carotid arteries is a strong predictor for cardiovascular events in the general
      population and dialysis patients. However, it is unclear whether carotid IMT is
      useful for the prediction of cardiovascular events in predialysis patients with
      CKD. The prediction power of carotid ultrasonography for cardiovascular event,
      rate of renal function decline, and all-cause mortality was tested in a cohort of
      203 Chinese patients with stages 3 to 4 CKD. The average IMT was 0.808 +/- 0.196
      mm; 121 (59.6%) patients had atherosclerotic plaques visualized. IMT correlated
      with patient age (r = 0.373, P < 0.001), serum LDL level (r = 0.164, P = 0.021),
      Charlson's comorbidity score (r = 0.260, P < 0.001), and serum C-reactive protein
      (r = 0.279, P < 0.001). Carotid IMT was significantly higher in patients with
      diabetes than in those without diabetes (0.930 +/- 0.254 versus 0.794 +/- 0.184;
      P = 0.002). At 48 mo, the cardiovascular event-free survival was 94.4, 89.8,
      77.7, and 65.9% for IMT quartiles I, II, III, and IV, respectively (log rank
      test, P = 0.006). By multivariate analysis with the Cox proportional hazard
      model, each higher quartile of IMT conferred 41.6% (95% confidence interval 6.4
      to 88.4%; P = 0.017) excess hazard for developing cardiovascular event. The
      actuarial survival at 48 mo was 96.3, 98.0, 95.7, and 85.7% for IMT quartiles I,
      II, III and IV, respectively (log rank test, P = 0.127), and the difference was
      not statistically significant after Cox proportional hazard model to adjust for
      confounders. Carotid IMT did not correlate with the rate of renal function
      decline in these patients. Carotid IMT is a strong predictor of cardiovascular
      disease in Chinese predialysis patients and may be usefully applied for risk
      stratification in this group of patients.

PMID- 17494887
TI  - Slowly progressive, angiotensin II-independent glomerulosclerosis in human
      (pro)renin receptor-transgenic rats.
AB  - For defining the pathogenic effects of the (pro)renin receptor-transgenic rat,
      strains that overexpressed the human receptor were generated. Although transgenic
      rats were normotensive and euglycemic and had a renal angiotensin II (AngII)
      level that was comparable to that of wild-type rats, transgenic rats developed
      proteinuria with aging and significant glomerulosclerosis at 28 wk of age. In
      kidneys of 28-wk-old transgenic rats, mitogen-activated protein kinases (MAPK)
      were activated without recognizable tyrosine phosphorylation of the EGF receptor,
      and expression of TGF-beta1 was enhanced. In vivo infusion of the (pro)renin
      receptor blocker peptide (formerly handle region decoy peptide) significantly
      inhibited the development of glomerulosclerosis, proteinuria, MAPK activation,
      and TGF-beta1 expression in the kidneys, but the angiotensin-converting enzyme
      inhibitor did not attenuate these changes despite a significant decrease in the
      renal AngII level. In addition, recombinant rat prorenin stimulated MAPK
      activation in the human receptor-expressed cultured cells, but human receptor was
      unable to evoke the enzyme activity of rat prorenin. Thus, human (pro)renin
      receptor elicits slowly progressive nephropathy by AngII-independent MAPK
      activation in rats. This study clearly provided in vivo evidence for the AngII
      independent MAPK activation by human (pro)renin receptor and induction of
      glomerulosclerosis with increased TGF-beta1 expression.

PMID- 17494888
TI  - Selective binding and presentation of CCL5 by discrete tissue microenvironments
      during renal inflammation.
AB  - T cells are differentially recruited to the tubulointerstitium during renal
      inflammation. The selective presentation of chemokines by surface structures may
      in part underlie this phenomenon. In an attempt to better characterize the
      presentation of chemokines by tissue environments an exemplary chemokine with a
      well-defined structure was selected, and a binding assay for the protein on fixed
      archival tissue sections was developed. This article describes the selective
      binding of the chemokine CCL5 to renal structures. CCL5 was shown to bind to
      endothelial regions, interstitial extracellular matrix, tubular epithelial cells,
      and tubular basement membranes but rarely to glomerular structures in well
      preserved kidneys. In contrast, binding of CCL5 to glomerular components was seen
      in renal biopsies with acute allograft glomerulitis (in which T cells accumulate
      in glomeruli). The N terminus mediates receptor binding, whereas two clusters of
      basic amino acid residues ((44)RKNR(47) and (55)KKWVR(59)) are involved in the
      presentation of CCL5 by extracellular structures. Mutation of either loop
      abrogated CCL5 binding to tissue sections. Variations of the N terminus and a
      mutation that prevents higher order oligomerization did not change the binding
      pattern. The data suggest that renal compartments differ in their capacity to
      present chemokines, which may help explain the differential recruitment of
      leukocytes during allograft injury. Both clusters of basic residues in CCL5 are
      necessary for sufficient binding of CCL5 to tissue sections.

PMID- 17494889
TI  - Hospital protocols for targeted glycemic control: Development, implementation,
      and models for cost justification.
AB  - PURPOSE: Evolving elements of best practices for providing targeted glycemic
      control in the hospital setting, clinical performance measurement, basal-bolus
      plus correction-dose insulin regimens, components of standardized subcutaneous
      (s.c.) insulin order sets, and strategies for implementation and cost
      justification of glycemic control initiatives are discussed. SUMMARY: Best
      practices for targeted glycemic control should address accurate documentation of
      hyperglycemia, initial patient assessment, management plan, target blood glucose
      range, blood glucose monitoring frequency, maintenance of glycemic control,
      criteria for glucose management consultations, and standardized insulin order
      sets and protocols. Establishing clinical performance measures, including
      desirable processes and outcomes, can help ensure the success of targeted
      hospital glycemic control initiatives. The basal-bolus plus correction-dose
      regimen for insulin administration will be used to mimic the normal physiologic
      pattern of endogenous insulin secretion. Standardized insulin order sets and
      protocols are being used to minimize the risk of error in insulin therapy.
      Components of standardized s.c. insulin order sets include specification of the
      hyperglycemia diagnosis, finger stick blood glucose monitoring frequency and
      timing, target blood glucose concentration range, cutoff values for excessively
      high or low blood glucose concentrations that warrant alerting the physician,
      basal and prandial or nutritional (i.e., bolus) insulin, correction doses,
      hypoglycemia treatment, and perioperative or procedural dosage adjustments. The
      endorsement of hospital administrators and key physician and nursing leaders is
      needed for glycemic control initiatives. Initiatives may be cost justified on the
      basis of the billings for clinical diabetes management services and/or the return
      on-investment accrued to reductions in hospital length of stay, readmissions,
      and accurate documentation and coding of unrecognized or uncontrolled diabetes,
      and diabetes complications. CONCLUSION: Standardized insulin order sets and
      protocols may minimize risk of insulin errors. The endorsement of these protocols
      by administrators, physicians, nurses, and pharmacists is also needed for
      success.

PMID- 17494892
TI  - Etiology and effect on outcomes of hyperglycemia in hospitalized patients.
AB  - PURPOSE: The prevalence of diabetes in U.S. hospitals, etiology and
      pathophysiology of hyperglycemia in hospitalized patients, impact of
      hyperglycemia on patient outcomes, and benefits of hyperglycemia correction are
      described. SUMMARY: Diabetes mellitus is a common and costly condition with an
      increasing prevalence in the U.S. Hyperglycemia is common among hospital patients
      with and without diabetes. Possible causes of hyperglycemia include illness
      related metabolic stress, parenteral nutrition, and pharmacotherapy. The
      deposition of advanced glycosylation end products, capillary basement membrane
      thickening, impaired immune function, oxidative stress, impaired lipid
      metabolism, prothrombotic changes, activation of protein kinase C-beta, vascular
      leakage, capillary non perfusion, and induction of vascular endothelial growth
      factor are among the harmful effects of hyperglycemia. In various types of
      patients and hospital settings, hyperglycemia increases the mortality rate, risk
      of postoperative nosocomial infection, need for intensive care unit admission,
      length of hospital stay, and hospital charges. The benefits of using intensive
      therapy to correct hyperglycemia in hospitalized patients in reducing mortality
      and the risk of infections and other adverse outcomes are well documented.
      CONCLUSION: Efforts are needed to manage hyperglycemia in hospitalized patients
      with and without diabetes to minimize the morbidity, mortality, and costs
      associated with hyperglycemia.

PMID- 17494893
TI  - Hyperglycemia management in the hospital setting.
AB  - PURPOSE: Recommendations for target blood glucose concentrations; factors that
      can complicate glycemic control; considerations that determine the aggressiveness
      of therapy to manage blood glucose levels; the role of oral antihyperglycemic
      drug therapy, sliding-scale insulin, continuous intravenous (i.v.) insulin
      infusions, and basal-bolus insulin therapy; the pharmacodynamics of various
      insulin products; computer decision support systems; and discharge planning for
      hospitalized patients with hyperglycemia are described. SUMMARY: Target blood
      glucose concentrations depend on whether patients are critically ill or not.
      Factors that can complicate glycemic control include the severity of illness,
      medications, and inconsistent dietary intake. The expected course of treatment,
      anticipated length of stay, and preadmission glycemic control influence the
      aggressiveness of therapy to manage hyperglycemia. The usefulness of oral
      antihyperglycemic agents for managing in-hospital hyperglycemia is limited by
      difficulty titrating the dosage and promptly achieving target blood glucose
      concentrations. Sliding-scale insulin is not recommended because it is
      ineffective and potentially dangerous. Continuous i.v. insulin therapy or
      intermittent subcutaneous (s.c.) basal-bolus plus correction injections is
      preferred. Basal-bolus plus correction insulin therapy usually involves a single
      daily dose of insulin glargine at bedtime to prevent gluconeogenesis and
      ketogenesis, bolus injections of a rapid-acting insulin shortly before or after
      meals to meet prandial requirements, and correction bolus injections of rapid
      acting insulin as needed for blood glucose elevations before or between meals.
      Hypoglycemia is the primary limiting factor for achieving optimal glycemic
      control with insulin therapy. Computer decision support systems can help reduce
      the risk of insulin infusion rate calculation errors and standardize insulin
      therapy. Communication with the primary care physician in the outpatient setting
      is an important part of discharge planning. CONCLUSION: Sliding-scale insulin is
      not effective. Continuous i.v. insulin therapy or intermittent s.c. basal-bolus
      plus correction injections is preferred. Proactive management of hyperglycemia
      using these methods is needed to achieve and maintain glycemic control in
      hospitalized patients.

PMID- 17494894
TI  - Few options available for arthritis pain relief. FDA declines to approve Merck's
      Arcoxia.

PMID- 17494895
TI  - Novartis suspends tegaserod sales at FDA's request.

PMID- 17494898
TI  - New Medicare rule hedges on requiring pharmacist on transplantation team.

PMID- 17494896
TI  - Cost savings just one issue in infection control.

PMID- 17494900
TI  - Hospital admission associated with Medicare Part D "doughnut hole".

PMID- 17494901
TI  - Pursuing a faculty position.

PMID- 17494902
TI  - Cinnamon in diabetes mellitus.

PMID- 17494903
TI  - Medical marijuana and the developing role of the pharmacist.
AB  - PURPOSE: The pharmacology, therapeutic uses, safety, drug-drug interactions, and
      drug-disease interactions of medical marijuana are reviewed, and the legal issues
      related to its use and the implications of medical marijuana for the pharmacist
      are presented. SUMMARY: Marijuana contains more than 460 active chemicals and
      over 60 unique cannabinoids. The legal landscape surrounding marijuana is
      surprisingly complex and unsettled. In the United States, 11 states and several
      municipalities have legalized medical marijuana. Another state provides
      legislation that allows patients to claim a defense of medical necessity.
      Nevertheless, patients using medical marijuana may never interact with a
      pharmacist. Marijuana is a Schedule I controlled substance and its use is illegal
      under federal law. Marijuana has a number of purported therapeutic uses with a
      broad range of supporting evidence. There are five general indications for
      medical marijuana: (1) severe nausea and vomiting associated with cancer
      chemotherapy or other causes, (2) weight loss associated with debilitating
      illnesses, including HIV infection and cancer, (3) spasticity secondary to
      neurologic diseases, such as multiple sclerosis, (4) pain syndromes, and (5)
      other uses, such as for glaucoma. Marijuana is associated with adverse
      psychiatric, cardiovascular, respiratory, and immunologic events. Moreover,
      marijuana may interact with a number of prescription drugs and concomitant
      disease states. CONCLUSION: Several states have legalized the use of marijuana
      for chronic and debilitating medication conditions. Pharmacists need to
      understand the complex legal framework surrounding this issue so that they can
      protect themselves and better serve their patients.

PMID- 17494904
TI  - Quetiapine for acute mania in bipolar disorder.
AB  - PURPOSE: The efficacy and tolerability of quetiapine in the treatment of acute
      mania were reviewed. SUMMARY: Five randomized, placebo-controlled trials
      involving quetiapine as monotherapy or adjunct therapy in combination with either
      divalproex or lithium in the treatment of bipolar mania in either adolescents or
      adults were identified and reviewed. The primary outcome measure used in the
      trials was a change in Young Mania Rating Scale total scores. Monotherapy trials
      evaluated quetiapine, lithium, haloperidol, and placebo. Quetiapine was superior
      to placebo in both trials. Quetiapine and lithium showed comparable efficacy in
      one study, though lithium serum concentrations may have been suboptimal.
      Haloperidol was superior to quetiapine in efficacy at day 21 but similar at day
      84. In the two trials evaluating quetiapine or placebo as adjunct therapy to
      lithium or divalproex, quetiapine was significantly more efficacious than placebo
      in one trial. In adolescents, quetiapine was more effective than placebo as an
      adjunct to divalproex. The most common adverse effects clearly attributable to
      quetiapine in these trials were somnolence and dry mouth. Quetiapine did not
      induce extrapyramidal effects, but weight gain was notable with the drug.
      CONCLUSION: While quetiapine treatment demonstrated efficacy in the majority of
      the studies, the robustness of its efficacy is questionable. The use of
      quetiapine as first-line therapy for acute mania is not recommended based on the
      available results and cost considerations. However, it may be a useful second
      line agent, particularly when sensitivity to extrapyramidal symptoms limits
      treatment options.

PMID- 17494905
TI  - Association between common asthma therapies and recurrent asthma exacerbations in
      children enrolled in a state Medicaid plan.
AB  - PURPOSE: To evaluate the effectiveness of budesonide inhalation suspension
      relative to other common asthma therapies in a high-risk population, a study was
      conducted to compare the risk of having a repeat asthma-related hospitalization
      or emergency department (ED) visit in a Medicaid population of children; the
      relationship between asthma medication adherence level and repeat asthma
      hospitalizations or ED visits was also evaluated. METHODS: Children eight years
      of age or younger, with a hospitalization or ED visit for asthma between January
      1999 and June 2001 (index event), were identified in a Florida Medicaid database.
      Claims data for each child were examined 12 months before and after the index
      event. Cox proportional hazards regression was used to model the risk of
      subsequent asthma exacerbation according to the asthma medication received during
      the first 30 days after the index event. Logistic regression was used to model
      the relationship between medication adherence as measured by the medication
      possession ratio (MPR) and the likelihood of a subsequent asthma exacerbation.
      RESULTS: There were 10,976 children in the study. Patients who had a claim for
      budesonide inhalation suspension had a lower risk of a subsequent hospitalization
      or ED visit (hazard ratio, 0.55; 95% confidence interval, 0.41-0.76; p < 0.001)
      than patients who did not have budesonide inhalation suspension claims. Other
      controller medications were not associated with a reduction in the risk of
      subsequent asthma exacerbations. Adherence to medication was poor (a median MPR
      of 0.08 for budesonide inhalation suspension and a median MPR of 0.16 for any
      asthma controller medication). The odds of a repeat hospitalization or ED visit
      were significantly lower for children who were adherent to their asthma
      controller medication. CONCLUSION: Children with asthma and insured by Medicaid
      were at a high risk of repeat exacerbations leading to increased hospitalizations
      and ED visits. Treatment with budesonide inhalation suspension in the first 30
      days after a hospitalization or ED visit for asthma was associated with a
      significant reduction in the risk of repeat asthma-related hospitalizations or ED
      visits during the following year. Children who were adherent to their asthma
      controller medication had significantly lower odds of having a subsequent asthma
      exacerbation.

PMID- 17494906
TI  - Characterization of prescribing errors in an internal medicine clinic.
AB  - PURPOSE: A pilot study was conducted to characterize the epidemiology of
      prescribing errors, comparing those that occurred pre- to postimplementation of
      an electronic prescribing system; this article describes the results of the study
      during the preimplementation phase, when a handwritten prescription process was
      still in place. SUMMARY: A retrospective review of 1411 prescriptions that were
      handwritten during a five-month time frame was used to identify and characterize
      medication errors and potential medication errors. The review was conducted in an
      internal medicine clinic in a large health system that was preparing to implement
      an electronic prescribing system. The first phase was the implementation of a
      basic system-one that facilitated the writing of a more complete and legible
      prescription. The second phase consisted of adding more sophisticated clinical
      decision support (CDS) capabilities. Three data sources were reviewed: the
      handwritten prescription, the electronic health record and the prescription as it
      had been entered into the pharmacy computer system. Almost 28% of the
      prescriptions evaluated contained one or more errors or potential errors. Over
      90% of the errors were potential errors. Only 0.2% of the errors caused patient
      harm. Non-clinical errors (illegibility, missing information, wrong dose) may be
      affected by a basic electronic prescribing system, and clinical errors (drug
      disease interaction, contraindication of a drug) may be affected only when more
      sophisticated levels of CDS programming are added. CONCLUSION: Potential
      prescribing errors occurred frequently but few reached the patient or caused
      harm. The most severe errors were those that may be reduced by the implementation
      of an electronic prescribing system with CDS capabilities.

PMID- 17494907
TI  - Implementing anticoagulation management by pharmacists in the inpatient setting.
AB  - PURPOSE: This article identifies approaches for implementing an inpatient
      anticoagulation program involving pharmacists; two successful inpatient
      anticoagulation programs previously reported in the literature are described with
      a discussion of steps to consider in developing or expanding such a service.
      SUMMARY: Two institutions implemented pharmacist-managed anticoagulation
      services. One institution identified an undesirable incidence of medication
      related adverse events occurring in hospitalized patients receiving
      anticoagulants. Pharmacists were asked to assist. Pharmacist activities included
      the selection of anticoagulants, patient education, verification of insurance
      coverage of the patient's anticoagulant, and coordination of follow-up.
      Physicians were available to assist. At the other institution, the department of
      pharmacy was asked by the orthopedic surgeons to manage warfarin for the
      prophylaxis against venous thromboembolism. The pharmacy department worked with
      the medical staff to gain approval of all policies, guidelines, and protocols to
      establish an anticoagulation service. Because of the success of the program, the
      pharmacy department expanded the service beyond warfarin. The steps to
      establishment of an anticoagulation service are described. The challenges facing
      such programs are discussed, including the potential anticoagulants in
      development that will create ongoing challenges in deciding which anticoagulation
      approach to use and in identifying patients for whom the newer agents may or may
      not be best suited. CONCLUSION: Requirements for establishing a successful
      inpatient anticoagulation management program included defining the pharmacist's
      role in identifying patient needs, gaining support from other health care
      professionals, designing a program that addresses the needs of the patients, and
      managing unanticipated issues.

PMID- 17494908
TI  - Comparative costs of ertapenem and piperacillin-tazobactam in the treatment of
      diabetic foot infections.
AB  - PURPOSE: To evaluate potential cost savings, trial data were used to determine
      the clinical outcomes for i.v. ertapenem given once daily and i.v. piperacillin
      tazobactam given every six hours daily in treating diabetic foot infections.
      METHODS: A cost-minimization analysis (CMA) was conducted on the drug-dosing data
      of the subset of patients enrolled in a recent double-blind randomized trial who
      were treated solely as inpatients and were clinically evaluable at fi nal
      assessment (n = 99). Cost per dose was calculated from (a) average hospital
      acquisition price per dose for ertapenem ($40.52) or piperacillin-tazobactam
      ($13.58), (b) average U.S. wages and benefits for labor, based on nine published
      time-and-motion studies of i.v. antibiotic preparation and administration
      ($3.10), and (c) consumable supplies, using a 40% discount off the manufacturer
      list price ($2.90). For each patient, the actual number of antibiotic doses given
      was multiplied by total cost per dose. RESULTS: There were no significant
      differences between antibiotic groups with respect to patient demographics,
      percentage with a severe wound, and mean days of i.v. therapy. Compared with
      piperacillin-tazobactam, patients treated with ertapenem received significantly
      fewer mean doses (25.5 versus 7.5; p < 0.0001) and lower antibiotic-related costs
      ($502.76 versus $355.55, respectively; p < 0.001). The $147.21 difference between
      groups accounts for approximately 3% of total hospital Medicare reimbursements
      for these infections. CONCLUSION: A CMA of treatment of diabetic foot infections
      showed that, compared with piperacillin-tazobactam given four times daily i.v.,
      ertapenem given once daily i.v. was associated with lower drug acquisition and
      supply costs and less time and labor devoted to preparation and administration of
      i.v. therapy.

PMID- 17494909
TI  - Medication history reconciliation by pharmacists in an inpatient behavioral
      health unit.
AB  - PURPOSE: The effectiveness of a pharmacy-obtained medication history on the
      medication reconciliation process in the behavioral health unit (BHU) of a
      community hospital was studied. METHODS: Patients admitted to the BHU of a 411
      bed, not-for-profit hospital from 6 a.m. on Monday through 12 p.m. on Friday from
      September 1, 2005, through October 6, 2005, were candidates for the study. Within
      18 hours of admission to the BHU and after the medication history had been
      obtained by a nurse, a pharmacy technician gathered patient demographic and
      medication information from the chart and the patient's medication bottles. Once
      the technician completed the documentation, the pharmacist was notified of a new
      admission. The pharmacist reviewed the collected documentation and patient chart
      before interviewing the patient. RESULTS: Of the 54 patients who met the study's
      inclusion criteria, 91% were seen by a pharmacist within 18 hours of admission.
      The mean +/- S.D. time delay to interview the patient was 11.6 +/- 5.1 hours.
      Pharmacists spent a mean of 13.9 minutes completing patients' medication
      histories. The mean +/- S.D. number of medications identified by nursing on
      admission was 4.0 +/- 3.2, compared with 5.3 +/- 3.7 identified by pharmacists (p
      < 0.05). The mean number of medication discrepancies identified per patient was
      2.9. Of the discrepancies, 48% were related to an omitted or incorrect
      medication, 31% to an omitted or incorrect dose, and 13% to an omitted or
      incorrect frequency; 8% were categorized as miscellaneous. CONCLUSION:
      Pharmacists' participation in obtaining patients' medication histories through
      chart review and patient interview increased the effectiveness of the medication
      reconciliation process in an inpatient BHU.

PMID- 17494910
TI  - Stability of phenylephrine hydrochloride injection in polypropylene syringes.
AB  - PURPOSE: The stability of extemporaneously prepared phenylephrine hydrochloride
      injection stored in polypropylene syringes was studied. METHODS: Dilution of
      phenylephrine hydrochloride to a nominal concentration of 100 mug/mL was
      performed under aseptic conditions by adding 100 mg of phenylephrine
      hydrochloride (total of 10 mL from two 5-mL 10-mg/mL vials) to 1000 mL of 0.9%
      sodium chloride injection. The resulting solution was drawn into 10-mL
      polypropylene syringes and sealed with syringe caps. The syringes were then
      frozen (-20 degrees C), refrigerated (3-5 degrees C), or kept at room temperature
      (23-25 degrees C). Four samples of each preparation were analyzed on days 0, 7,
      15, 21, and 30. Physical stability was assessed by visual examination. The pH of
      each syringe was also measured at each time point. Sterility of the samples was
      not assessed. Chemical stability of phenylephrine hydrochloride was evaluated
      using high-performance liquid chromatography. To demonstrate the stability
      indicating nature of the assay, forced degradation of phenylephrine was
      conducted. Samples were considered stable if there was less than 10% degradation
      of the initial concentration. RESULTS: Phenylephrine hydrochloride diluted to 100
      microg/mL with 0.9% sodium chloride injection was physically stable throughout
      the study. No precipitation was observed. Minimal to no degradation was observed
      over the 30-day study period. CONCLUSION: Phenylephrine hydrochloride diluted to
      a concentration of 100 mug/mL in 0.9% sodium chloride injection was stable for at
      least 30 days when stored in polypropylene syringes at -20 degrees C, 3-5 degrees
      C, and 23-25 degrees C.

PMID- 17494911
TI  - Designing and implementing a hospital-based vaccine standing orders program.
AB  - PURPOSE: An inpatient pneumococcal polysaccharide vaccine (PPV) vaccination
      program was designed and implemented to meet federal and state regulatory
      requirements and national vaccination goals. SUMMARY: In 2002, the Centers for
      Medicare and Medicaid Services published a final rule removing the federal
      requirement for an individual patient physician-signed order for the pneumococcal
      and influenza vaccines in Medicare- and Medicaid- participating hospitals. This
      statute authorized implementation of standing orders programs (SOPs) in health
      care institutions. At the University of Pittsburgh Medical Center-Presbyterian
      (UPMC-P), institutional vaccination rates and the existing mechanism for
      providing adult vaccinations were evaluated. At the peak of the program's
      effectiveness in 2000, in-hospital total vaccination rates were 31%; those rates
      fell to 15% by the end of 2003. To rectify this poor rate of vaccination, a
      multidisciplinary team convened to evaluate the existing program and to design
      the tools and processes for a conversion to a vaccine SOP. A standing order form
      was designed, and it was determined that the SOP should be pharmacy driven. As a
      result of the SOP, the PPV vaccination rate increased dramatically; in 2005, the
      average rate was 69%, with the highest rate occurring in March 2005 (87%).
      CONCLUSION: The cooperative effort of a multidisciplinary work group including
      physicians, nursing staff, and pharmacy personnel led to the creation of a
      successful inpatient PPV SOP. Analysis of the previous vaccination program and
      careful planning were instrumental in designing the SOP. Defined responsibilities
      for daily performance and user-friendly tools with clear instructions were also
      crucial to the success of the program.

PMID- 17494912
TI  - What it means to be free.

PMID- 17494913
TI  - Paternal pronuclear DNA degradation is functionally linked to DNA replication in
      mouse oocytes.
AB  - We recently demonstrated that mouse spermatozoa contain a mechanism to degrade
      their DNA into loop-sized fragments of about 50 kb, mediated by topoisomerase
      IIB, termed sperm chromatin fragmentation (SCF). SCF is often followed by a more
      complete digestion of the DNA with a sperm nuclease. When SCF-induced spermatozoa
      are injected into oocytes, the paternal pronuclei degrade their DNA after the
      initiation of DNA synthesis, but the maternal pronuclei are unaffected and
      replicate normally. Here, we tested whether the nuclease activity changes in
      spermatozoa of different maturation stages, and whether there is a functional
      relationship between the initiation of DNA synthesis and paternal DNA degradation
      induced by SCF in the zygote. We found that spermatozoa from the vas deferens
      have a much higher level of SCF activity than those from the cauda epididymis,
      suggesting that spermatozoa may acquire this activity in the vas deferens.
      Furthermore, paternal pronuclei formed in zygotes from injecting oocytes with SCF
      induced vas deferens spermatozoa degraded their DNA, but this degradation could
      be inhibited by the DNA synthesis inhibitor, aphidicolin. Upon release from a 4 h
      aphidicolin-induced arrest, DNA synthesis was initiated in maternal pronuclei,
      while the paternal pronuclei degraded their DNA. Longer aphidicolin arrest
      resulted in the paternal pronuclei replicating their DNA, suggesting that
      delaying the initiation of DNA synthesis allowed the paternal pronuclei to
      overcome the SCF-induced DNA degradation pathway. These results suggest that the
      paternal DNA degradation, in oocytes fertilized with SCF-induced spermatozoa, is
      coupled to the initiation of DNA synthesis in newly fertilized zygotes.

PMID- 17494914
TI  - Microarray analyses of newborn mouse ovaries lacking Nobox.
AB  - Nobox is a homeobox gene expressed in oocytes and critical in oogenesis. Nobox
      deficiency leads to rapid loss of postnatal oocytes. Early oocyte differentiation
      is poorly understood. We hypothesized that lack of Nobox perturbs global
      expression of genes preferentially expressed in oocytes as well as microRNAs. We
      compared Nobox knockout and wild-type ovaries using Affymetrix 430 2.0 microarray
      platform. We discovered that 28 (74%) of 38 of the genes downregulated more than
      5-fold in the absence of Nobox were preferentially expressed in oocytes, whereas
      only 5 (15%) of 33 genes upregulated more than 5-fold in the absence of Nobox
      were preferentially expressed in oocytes. Protein-binding microarray helped
      identify nucleotide motifs that NOBOX binds and that several downregulated genes
      contain within putative promoter regions. MicroRNA population in newborn ovaries
      deficient of Nobox was largely unaffected. Genes whose proteins are predicted to
      be secreted but were previously unknown to be significantly expressed in early
      oogenesis were downregulated in Nobox knockouts and included astacin-like
      metalloendopeptidase (Astl), Jagged 1 (Jag1), oocyte-secreted protein 1 (Oosp1),
      fetuin beta (Fetub), and R-spondin 2 (Rspo2). In addition, pluripotency
      associated genes Pou5f1 and Sall4 are drastically downregulated in Nobox
      deficient ovaries, whereas testes-determining gene Dmrt1 is overexpressed. Our
      findings indicate that Nobox is likely an activator of oocyte-specific gene
      expression and suggest that the oocyte plays an important role in suppressing
      expression of male-determining genes, such as Dmrt1.

PMID- 17494915
TI  - Wild fulvous fruit bats (Rousettus leschenaulti) exhibit human-like menstrual
      cycle.
AB  - We investigated the menstrual cycle of wild fulvous fruit bats (Rousettus
      leschenaulti), focusing on changes in the endometrial and ovarian structure and
      pituitary and steroid hormones. The menstrual cycle lasts for 33 days in bats
      studied in their natural habitat and in captivity. Vaginal bleeding was
      restricted to a single day (Day 1). A preovulatory follicle was found in the
      ovary on Day 18 when the levels of LH and FSH reached their maxima, accompanied
      by a thickened endometrium. On Day 24, serum levels of progesterone and estradiol
      17 were also maximal, and uterine glands increased in size. After that, the
      levels of progesterone dropped precipitously, leading to menstrual bleeding. Both
      the morphologic and hormonal changes observed in fulvous fruit bats during the
      menstrual cycle resemble similar changes in humans. Fulvous fruit bats may be
      useful nonprimate laboratory models to study menstruation and menstrual
      dysfunction.

PMID- 17494916
TI  - Role of PI3-kinase and PI4-kinase in actin polymerization during bovine sperm
      capacitation.
AB  - We have recently demonstrated the involvement of phospholipase D (PLD) in actin
      polymerization during mammalian sperm capacitation. In the present study, we
      investigated the involvement of phosphatidylinositol 3- and 4-kinases (PI3K and
      PI4K) in actin polymerization, as well as the production of PIP(2(4,5)), which is
      a known cofactor for PLD activation, during bovine sperm capacitation. PIK3R1
      (p85 alpha regulatory subunit of PI3K) and PIKCB (PI4K beta) in bovine sperm were
      detected by Western blotting and immunocytochemistry. Wortmannin (WT) inhibited
      PI3K and PI4K type III at concentrations of 10 nM and 10 microM, respectively.
      PI4K activity and PIP(2(4,5)) production were blocked by 10 microM WT but not by
      10 nM WT, whereas PI3K activity and PIP(3(3,4,5)) production were blocked by 10
      nM WT. Moreover, spermine, which is a known PI4K activator and a component of
      semen, activated sperm PI4K, resulting in increased cellular PIP(2(4,5)) and F
      actin formation. The increases in PIP(2(4,5)) and F-actin intracellular levels
      during sperm capacitation were mediated by PI4K but not by PI3K activity.
      Activation of protein kinase A (PKA) by dibutyryl cAMP enhanced PIP(2(4,5)),
      PIP(3(3,4,5)), and F-actin formation, and these effects were mediated through
      PI3K. On the other hand, activation of PKC by phorbol myristate acetate enhanced
      PIP(2(4,5)) and F-actin formation mediated by PI4K activity, while the PI3K
      activity and intracellular PIP(3(3,4,5)) levels were reduced. These results
      suggest that two alternative pathways lead to PI4K activation: indirect
      activation by PKA, which is mediated by PI3K; and activation by PKC, which is
      independent of PI3K activity. Our results also suggest that spermine, which is
      present in the ejaculate, regulates PI4K activity during the capacitation process
      in vivo.

PMID- 17494917
TI  - Stem cells derived from human fetal membranes display multilineage
      differentiation potential.
AB  - The amnion is the inner of two membranes surrounding the fetus. That it arises
      from embryonic epiblast cells prior to gastrulation suggests that it may retain a
      reservoir of stem cells throughout pregnancy. We found that human amniotic
      epithelial cells (hAECs) harvested from term-delivered fetal membranes express
      mRNA and proteins present in human embryonic stem cells (hESCs), including POU
      domain, class 5, transcription factor 1; Nanog homeobox; SRY-box 2; and stage
      specific embryonic antigen-4. In keeping with possible stem cell-like activity,
      hAECs were also clonogenic, and primary hAEC cultures could be induced to
      differentiate into cardiomyocytic, myocytic, osteocytic, adipocytic (mesodermal),
      pancreatic, hepatic (endodermal), neural, and astrocytic (neuroectodermal) cells
      in vitro, as defined by phenotypic, mRNA expression, immunocytochemical, and/or
      ultrastructural characteristics. However, unlike hESCs, hAECs did not form
      teratomas upon transplantation into severe combined immunodeficiency mice testes.
      Last, using flow cytometry we have shown that only a very small proportion of
      primary hAECs contain class IA and class II human leukocyte antigens (HLAs),
      consistent with a low risk of tissue rejection. However, following
      differentiation into hepatic and pancreatic lineages, significant proportions of
      cells contained class IA, but not class II, HLAs. These observations suggest that
      the term amnion, an abundant and easily accessible tissue, may be a useful source
      of multipotent stem cells that possess a degree of immune privilege.

PMID- 17494918
TI  - The role of trehalose biosynthesis in plants.

PMID- 17494919
TI  - Solar UV radiation drives CO2 fixation in marine phytoplankton: a double-edged
      sword.

PMID- 17494920
TI  - Soybean root suberin: anatomical distribution, chemical composition, and
      relationship to partial resistance to Phytophthora sojae.
AB  - Soybean (Glycine max L. Merr.) is a versatile and important agronomic crop grown
      worldwide. Each year millions of dollars of potential yield revenues are lost due
      to a root rot disease caused by the oomycete Phytophthora sojae (Kaufmann &
      Gerdemann). Since the root is the primary site of infection by this organism, we
      undertook an examination of the physicochemical barriers in soybean root, namely,
      the suberized walls of the epidermis and endodermis, to establish whether or not
      preformed suberin (i.e. naturally present in noninfected plants) could have a
      role in partial resistance to P. sojae. Herein we describe the anatomical
      distribution and chemical composition of soybean root suberin as well as its
      relationship to partial resistance to P. sojae. Soybean roots contain a state I
      endodermis (Casparian bands only) within the first 80 mm of the root tip, and a
      state II endodermis (Casparian bands and some cells with suberin lamellae) in
      more proximal regions. A state III endodermis (with thick, cellulosic, tertiary
      walls) was not present within the 200-mm-long roots examined. An exodermis was
      also absent, but some walls of the epidermal and neighboring cortical cells were
      suberized. Chemically, soybean root suberin resembles a typical suberin, and
      consists of waxes, fatty acids, omega-hydroxy acids, alpha,omega-diacids, primary
      alcohols, and guaiacyl- and syringyl-substituted phenolics. Total suberin
      analysis of isolated soybean epidermis/outer cortex and endodermis tissues
      demonstrated (1) significantly higher amounts in the endodermis compared to the
      epidermis/outer cortex, (2) increased amounts in the endodermis as the root
      matured from state I to state II, (3) increased amounts in the epidermis/outer
      cortex along the axis of the root, and (4) significantly higher amounts in
      tissues isolated from a cultivar ('Conrad') with a high degree of partial
      resistance to P. sojae compared with a susceptible line (OX760-6). This latter
      correlation was extended by an analysis of nine independent and 32 recombinant
      inbred lines (derived from a 'Conrad' x OX760-6 cross) ranging in partial
      resistance to P. sojae: Strong negative correlations (-0.89 and -0.72,
      respectively) were observed between the amount of the aliphatic component of root
      suberin and plant mortality in P. sojae-infested fields.

PMID- 17494921
TI  - Images in clinical medicine. Lymphomatous infiltration of the eyelids.

PMID- 17494922
TI  - Politics, parents, and prophylaxis--mandating HPV vaccination in the United
      States.

PMID- 17494923
TI  - Introducing HPV vaccine in developing countries--key challenges and issues.

PMID- 17494924
TI  - Legal regulation of physician-assisted death--the latest report cards.

PMID- 17494925
TI  - Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical
      lesions.
AB  - BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause
      approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to
      evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV
      6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV
      16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned
      12,167 women between the ages of 15 and 26 years to receive three doses of either
      HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6.
      The primary analysis was performed for a per-protocol susceptible population that
      included 5305 women in the vaccine group and 5260 in the placebo group who had no
      virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the
      third dose (month 7). The primary composite end point was cervical
      intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical
      cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an
      average of 3 years after receiving the first dose of vaccine or placebo. Vaccine
      efficacy for the prevention of the primary composite end point was 98% (95.89%
      confidence interval [CI], 86 to 100) in the per-protocol susceptible population
      and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who
      had undergone randomization (those with or without previous infection). The
      estimated vaccine efficacy against all high-grade cervical lesions, regardless of
      causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31).
      CONCLUSIONS: In young women who had not been previously infected with HPV-16 or
      HPV-18, those in the vaccine group had a significantly lower occurrence of high
      grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did
      those in the placebo group. (ClinicalTrials.gov number, NCT00092534
      [ClinicalTrials.gov].).

PMID- 17494926
TI  - Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.
AB  - BACKGROUND: A phase 3 trial was conducted to evaluate the efficacy of a
      prophylactic quadrivalent vaccine in preventing anogenital diseases associated
      with human papillomavirus (HPV) types 6, 11, 16, and 18. METHODS: In this
      randomized, placebo-controlled, double-blind trial involving 5455 women between
      the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732
      to receive placebo at day 1, month 2, and month 6. The coprimary composite end
      points were the incidence of genital warts, vulvar or vaginal intraepithelial
      neoplasia, or cancer and the incidence of cervical intraepithelial neoplasia,
      adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data
      for the primary analysis were collected for a per-protocol susceptible population
      of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1
      month after administration of the third dose. RESULTS: The women were followed
      for an average of 3 years after administration of the first dose. In the per
      protocol population, those followed for vulvar, vaginal, or perianal disease
      included 2261 women (83%) in the vaccine group and 2279 (83%) in the placebo
      group. Those followed for cervical disease included 2241 women (82%) in the
      vaccine group and 2258 (83%) in the placebo group. Vaccine efficacy was 100% for
      each of the coprimary end points. In an intention-to-treat analysis, including
      those with prevalent infection or disease caused by vaccine-type and non-vaccine
      type HPV, vaccination reduced the rate of any vulvar or vaginal perianal lesions
      regardless of the causal HPV type by 34% (95% confidence interval [CI], 15 to
      49), and the rate of cervical lesions regardless of the causal HPV type by 20%
      (95% CI, 8 to 31). CONCLUSIONS: The quadrivalent vaccine significantly reduced
      the incidence of HPV-associated anogenital diseases in young women.
      (ClinicalTrials.gov number, NCT00092521 [ClinicalTrials.gov].).

PMID- 17494927
TI  - Case-control study of human papillomavirus and oropharyngeal cancer.
AB  - BACKGROUND: Substantial molecular evidence suggests a role for human
      papillomavirus (HPV) in the pathogenesis of oropharyngeal squamous-cell
      carcinoma, but epidemiologic data have been inconsistent. METHODS: We performed a
      hospital-based, case-control study of 100 patients with newly diagnosed
      oropharyngeal cancer and 200 control patients without cancer to evaluate
      associations between HPV infection and oropharyngeal cancer. Multivariate
      logistic-regression models were used for case-control comparisons. RESULTS: A
      high lifetime number of vaginal-sex partners (26 or more) was associated with
      oropharyngeal cancer (odds ratio, 3.1; 95% confidence interval [CI], 1.5 to 6.5),
      as was a high lifetime number of oral-sex partners (6 or more) (odds ratio, 3.4;
      95% CI, 1.3 to 8.8). The degree of association increased with the number of
      vaginal-sex and oral-sex partners (P values for trend, 0.002 and 0.009,
      respectively). Oropharyngeal cancer was significantly associated with oral HPV
      type 16 (HPV-16) infection (odds ratio, 14.6; 95% CI, 6.3 to 36.6), oral
      infection with any of 37 types of HPV (odds ratio, 12.3; 95% CI, 5.4 to 26.4),
      and seropositivity for the HPV-16 L1 capsid protein (odds ratio, 32.2; 95% CI,
      14.6 to 71.3). HPV-16 DNA was detected in 72% (95% CI, 62 to 81) of 100 paraffin
      embedded tumor specimens, and 64% of patients with cancer were seropositive for
      the HPV-16 oncoprotein E6, E7, or both. HPV-16 L1 seropositivity was highly
      associated with oropharyngeal cancer among subjects with a history of heavy
      tobacco and alcohol use (odds ratio, 19.4; 95% CI, 3.3 to 113.9) and among those
      without such a history (odds ratio, 33.6; 95% CI, 13.3 to 84.8). The association
      was similarly increased among subjects with oral HPV-16 infection, regardless of
      their tobacco and alcohol use. By contrast, tobacco and alcohol use increased the
      association with oropharyngeal cancer primarily among subjects without exposure
      to HPV-16. CONCLUSIONS: Oral HPV infection is strongly associated with
      oropharyngeal cancer among subjects with or without the established risk factors
      of tobacco and alcohol use.

PMID- 17494929
TI  - Sodium and potassium in the pathogenesis of hypertension.

PMID- 17494928
TI  - End-of-life practices in the Netherlands under the Euthanasia Act.
AB  - BACKGROUND: In 2002, an act regulating the ending of life by a physician at the
      request of a patient with unbearable suffering came into effect in the
      Netherlands. In 2005, we performed a follow-up study of euthanasia, physician
      assisted suicide, and other end-of-life practices. METHODS: We mailed
      questionnaires to physicians attending 6860 deaths that were identified from
      death certificates. The response rate was 77.8%. RESULTS: In 2005, of all deaths
      in the Netherlands, 1.7% were the result of euthanasia and 0.1% were the result
      of physician-assisted suicide. These percentages were significantly lower than
      those in 2001, when 2.6% of all deaths resulted from euthanasia and 0.2% from
      assisted suicide. Of all deaths, 0.4% were the result of the ending of life
      without an explicit request by the patient. Continuous deep sedation was used in
      conjunction with possible hastening of death in 7.1% of all deaths in 2005,
      significantly increased from 5.6% in 2001. In 73.9% of all cases of euthanasia or
      assisted suicide in 2005, life was ended with the use of neuromuscular relaxants
      or barbiturates; opioids were used in 16.2% of cases. In 2005, 80.2% of all cases
      of euthanasia or assisted suicide were reported. Physicians were most likely to
      report their end-of-life practices if they considered them to be an act of
      euthanasia or assisted suicide, which was rarely true when opioids were used.
      CONCLUSIONS: The Dutch Euthanasia Act was followed by a modest decrease in the
      rates of euthanasia and physician-assisted suicide. The decrease may have
      resulted from the increased application of other end-of-life care interventions,
      such as palliative sedation.

PMID- 17494930
TI  - Images in clinical medicine. Severe proliferative diabetic retinopathy.

PMID- 17494931
TI  - Case records of the Massachusetts General Hospital. Case 14-2007. A 59-year-old
      man with fever and pain and swelling of both eyes and the right ear.

PMID- 17494932
TI  - Human papillomavirus vaccine--opportunity and challenge.

PMID- 17494933
TI  - HPV vaccination--more answers, more questions.

PMID- 17494934
TI  - Human papillomaviruses in head and neck carcinomas.

PMID- 17494935
TI  - Cancer regression by senescence.

PMID- 17494936
TI  - Mandating HPV vaccination--private rights, public good.

PMID- 17494937
TI  - Treatment of infertility in the polycystic ovary syndrome.

PMID- 17494938
TI  - GM-CSF autoantibodies in pulmonary alveolar proteinosis.

PMID- 17494939
TI  - Communicating about dying in the ICU.

PMID- 17494940
TI  - Interleukin-12/23 monoclonal antibody for psoriasis.

PMID- 17494941
TI  - The incidentally discovered adrenal mass.

PMID- 17494942
TI  - Urine fluorescence in ethylene glycol poisoning.

PMID- 17494943
TI  - Superior athletic performance two decades after cardiac transplantation.

PMID- 17494946
TI  - Using GIS to facilitate community-based public health planning of diabetes
      intervention efforts.
AB  - Data from a community survey were analyzed geographically to help facilitate
      local diabetes prevention efforts. Data were available from the Speak to Your
      Health! Community Survey, designed and implemented by The Prevention Research
      Center of Michigan (PRC/MI), whose central mission is to strengthen community
      capacity to improve health. This survey was developed collaboratively by the
      university and community partners that comprise the PRC/MI and focuses on health
      and social issues at the heart of the community of Genesee County, Michigan.
      Survey data were used to calculate and geographically map diabetes-risk scores
      and mapped diabetes-screening rates. These maps indicated that those areas where
      the estimated risk of diabetes was the highest had only moderate rates of
      diabetes screening relative to other areas. It is hoped that these results will
      reach those involved in local diabetes-intervention programs with the intent that
      the data will be used in planning local prevention and intervention efforts.

PMID- 17494947
TI  - Building on the strengths of a Cambodian refugee community through community
      based outreach.
AB  - Literature and practice are limited on strategies to reach elder Southeast Asian
      refugees by using their strengths and resilience. This article presents the
      Centers for Disease Control and Prevention-funded Cambodian Community Health 2010
      Program in Lowell, Massachusetts, as a case example and provides refugee history,
      project background, community survey results about strengths and risks,
      literature on strengths-based approaches, outreach activities, and evaluation.
      The focus is elimination of health disparities in cardiovascular disease and
      diabetes. "Community conversations" and a daylong forum with community leaders
      were used to develop plans for outreach. A Cambodian Elders Council provided
      information and guidance used to refine the program. Key findings highlight
      involving elders in organizing events, avoiding reliance on literacy, integrating
      health promotion with socialization, using ties with Buddhist temples, developing
      transportation alternatives, and utilizing local Khmer-language media.
      Implications include applicability to other refugee communities with low
      literacy, high levels of trauma, limited English, and strong religious
      involvement.

PMID- 17494944
TI  - The proteome of the mouse photoreceptor sensory cilium complex.
AB  - Primary cilia play critical roles in many aspects of biology. Specialized
      versions of primary cilia are involved in many aspects of sensation. The single
      photoreceptor sensory cilium (PSC) or outer segment elaborated by each rod and
      cone photoreceptor cell of the retina is a classic example. Mutations in genes
      that encode cilia components are common causes of disease, including retinal
      degenerations. The protein components of mammalian primary and sensory cilia have
      not been defined previously. Here we report a detailed proteomics analysis of the
      mouse PSC complex. The PSC complex comprises the outer segment and its
      cytoskeleton, including the axoneme, basal body, and ciliary rootlet, which
      extends into the inner segment of photoreceptor cells. The PSC complex proteome
      contains 1968 proteins represented by three or more unique peptides, including
      approximately 1500 proteins not detected in cilia from lower organisms. This
      includes 105 hypothetical proteins and 60 proteins encoded by genes that map
      within the critical intervals for 23 inherited cilia-related disorders,
      increasing their priority as candidate genes. The PSC complex proteome also
      contains many cilia proteins not identified previously in photoreceptors,
      including 13 proteins produced by genes that harbor mutations that cause cilia
      disease and seven intraflagellar transport proteins. Analyses of PSC complexes
      from rootletin knock-out mice, which lack ciliary rootlets, confirmed that 1185
      of the identified PSC complex proteins are derived from the outer segment. The
      mass spectrometry data, benchmarked by 15 well characterized outer segment
      proteins, were used to quantify the copy number of each protein in a mouse rod
      outer segment. These results reveal mammalian cilia to be several times more
      complex than the cilia of unicellular organisms and open novel avenues for
      studies of how cilia are built and maintained and how these processes are
      disrupted in human disease.

PMID- 17494948
TI  - Recruitment strategies and costs for a community-based physical activity program.
AB  - A community-based participatory research project using social marketing
      strategies was implemented to promote physical activity among women aged 35 to 54
      who were insufficiently active or completely inactive. A variety of media were
      used to disseminate messages about how to enroll in Step Up. Step Out! This
      article describes the effectiveness and cost of the recruitment strategies and
      lessons learned in recruiting the women. Of the total inquiries (n = 691), 430
      women were eligible and enrolled in the program. Based on data from
      questionnaires, the most effective method of recruiting women into Step Up. Step
      Out! was word of mouth (36%). Newspaper ads accounted for 29% of the women's
      responses. The least effective method was billboards. Mass media was not as
      effective in recruiting women for the program as interpersonal efforts such as
      word of mouth. Interpersonal efforts are a valuable and possibly underrated
      recruitment and promotion tool.

PMID- 17494949
TI  - Translating efficacious behavioral principles for diabetes prevention into
      practice.
AB  - This case study describes the process of translating efficacy-based Diabetes
      Prevention Program principles into a practical format for delivery within a
      managed care organization. Using Rogers' innovation-decision process model, the
      authors tracked the adoption, implementation, and short-term effectiveness of a
      clinical program. Effectiveness was documented using a pre-post design to detect
      changes in physical activity and dietary habits. Participants (N = 298) were
      Kaiser Permanente of Colorado patients enrolled in diabetes-prevention classes.
      Changes were analyzed using paired-samples t tests and one-way analysis of
      variance. Participants significantly increased reported minutes of moderate (p <
      .001, mu = 84.52, CI: 58.44-110.61) and vigorous (t = 2.220, p = .028, mu =
      19.05, CI: 2.10-36.00) physical activity and their daily servings of fruits and
      vegetables (p < .001, mu = 0.20, CI: 0.13-0.27). By identifying the underlying
      strategies that led to efficacy, professionals can implement sound diabetes
      prevention programs that fit within their context.

PMID- 17494950
TI  - Formative evaluation of AARP's Active for Life campaign to improve walking and
      bicycling environments in two cities.
AB  - AARP conducted a 2.5-year social-marketing campaign to improve physical activity
      levels among older adults in Richmond, Virginia and Madison, Wisconsin. This
      article presents formative evaluation findings from the campaign's
      policy/environmental change component. Evaluation data were abstracted from
      technical-assistance documentation and telephone interviews. Results include 11
      policy and 14 environmental changes attained or in-process by campaign closure.
      Differences between the cities' results are explained through differences in
      program implementation (e.g., types of changes planned, formalization of
      partnerships). Project teams took less time deciding to pursue policy change than
      environmental change; however, planning the policy activities took longer than
      planning environmental-change activities. Recommendations for future
      policy/environmental change interventions focus on the selection of strategies;
      planning for administrative resources; formalizing partnerships to ensure
      sustainability of impact; ensuring training and technical assistance; and
      documenting progress. Similar intervention results may be attainable with a multi
      year timeframe, adequate part-time coordination, and committed volunteers.

PMID- 17494951
TI  - IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric
      oxide synthase mRNA by equine pulmonary artery endothelial cells.
AB  - Little is known concerning the possible contribution of T helper 2 (Th2)-type
      cytokines to the recruitment of neutrophils into the lung tissue. In the present
      study, endothelial cells from equine pulmonary arteries were cultured in the
      presence of recombinant equine (re) IL-4 and reIL-5, and the cytokine mRNA
      expression of molecules implicated in the chemotaxis and migration of neutrophils
      was studied using real-time RT-PCR. The functional response of reIL-4-induced
      endothelial cell stimulation on neutrophil migration was also studied using a
      chemotaxis chamber. ReIL-4 either increased the expression of CXCL-8, E-selectin,
      vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase
      (iNOS), or potentiated the coeffects of lipopolysaccharide (LPS) and tumor
      necrosis factor-alpha (TNF-alpha) on CXCL-8. Supernatants collected from cultured
      endothelial cells stimulated with reIL-4 significantly promoted neutrophil
      migration in a dose-dependent manner. Dexamethasone (DXM) decreased the
      expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W
      dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression
      of E-selectin, VEGF, and iNOS. DXM and 1400W attenuated the mRNA expression of E
      selectin and iNOS induced by the costimulation of reIL-4, reTNF-alpha, and LPS.
      Neither equine nor human recombinant IL-5 influenced the mRNA expression of CXCL
      8, E-selectin, or VEGF. These findings suggest that Th2-type cytokines may
      contribute to pulmonary neutrophilia during allergic inflammation by the
      increased expression of neutrophil chemokines and adhesion molecules by
      endothelial cells. DXM and the iNOS inhibitors may decrease pulmonary
      neutrophilia due, in part, to a direct inhibition of some of these factors.

PMID- 17494952
TI  - Effect of the endothelin receptor antagonist bosentan on chronic hypoxia-induced
      morphological and physiological changes in rat carotid body.
AB  - Previous experiments have repeatedly demonstrated that exposure to chronic
      hypoxia (CH) elicits remarkable structural changes and chemosensory
      hypersensitivity in the mammalian carotid body. Moreover, recent studies have
      shown that CH upregulates the neuroactive peptide, endothelin (ET), in oxygen
      sensitive type I cells. The present study examines the possible involvement of ET
      in adaptation by concurrently exposing rats to hypobaric CH (B(P) = 380 Torr) and
      bosentan, a potent nonpeptide antagonist that blocks ET(A) and ET(B) receptors.
      Carotid body weight indicated that 14 days of CH induced organ enlargement, a
      response that was blunted in bosentan-treated rats (CH: 2.54 +/- 0.19-fold
      increase; CH plus bosentan: 1.92 +/- 0.14-fold increase; P < 0.05). Morphometric
      studies revealed that bosentan substantially eliminated CH-induced hyperplasia of
      chemosensory cell lobules as well as expansion of the connective tissue matrix.
      Vascular dilation associated with CH was not altered by the drug. In untreated
      animals exposed to 3 days of CH, expression of proliferating cell nuclear antigen
      (PCNA), a marker of mitosis, was increased in lobules of oxygen-sensitive type I
      cells and in extralobular vascular and connective tissue cells. The incidence of
      PCNA expression was significantly (P < 0.05) reduced in bosentan-treated animals.
      In vitro assessments of carotid sinus nerve (CSN) activity showed that
      enhancement of basal and hypoxia-evoked chemosensory activity following 9 days of
      CH was significantly (P < 0.001) blunted by concurrent treatment with bosentan.
      Collectively, our data are consistent with the hypothesis that CH-induced
      adaptation in the carotid body is at least partially mediated by signaling
      pathways involving ET receptors.

PMID- 17494953
TI  - MAPK pathway mediates EGR-1-HSP70-dependent cigarette smoke-induced chemokine
      production.
AB  - Cigarette smoking, a major risk factor for chronic obstructive pulmonary disease,
      can cause airway inflammation, airway narrowing, and loss of elasticity, leading
      to chronic airflow limitation. In this report, we sought to define the signaling
      pathways activated by smoke and to identify molecules responsible for cigarette
      smoke-induced inflammation. We applied cigarette smoke water extract (CSE) to
      primary human lung fibroblasts and found that CSE significantly increased CXC
      chemokine IL-8 production. Meanwhile, 70-kDa heat shock protein (HSP70) was also
      induced by CSE in a dose- and time-dependent manner. CSE treatment stimulated
      HSP70 secretion by primary fibroblasts, which augmented IL-8 production. This was
      further confirmed by exogenously added recombinant HSP70. Using HSP70 small
      interfering RNA, we confirmed that CSE-induced chemokine production was dependent
      on heat shock protein expression. Further investigation showed that CSE could
      also stimulate early growth response-1 (EGR-1) in an ERK-dependent manner and
      that the expression of HSP70 was EGR-1 dependent. In view of these findings, we
      hypothesize that the MAPK-EGR-1-HSP70 pathway regulates the cigarette smoke
      induced inflammatory process.

PMID- 17494954
TI  - Novel pressure-to-cornea index in glaucoma.
AB  - BACKGROUND: Several conversion tables and formulas have been suggested to correct
      applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT
      is also thought to represent an independent glaucoma risk factor. In an attempt
      to integrate IOP and CCT into a unified risk factor and avoid uncertain
      correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is
      proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated
      IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal
      controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular
      hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was
      investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non
      glaucoma (controls+OHT) was compared with that of three published formulae for
      correcting IOP for CCT. Receiver operating characteristic (ROC) curves were
      built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD
      25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes
      within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were
      separately compared: control and NTG eyes as well as OHT and POAG eyes differed
      significantly. PCI demonstrated a larger area under the ROC curve (AUC) and
      significantly higher sensitivity at fixed 80% and 90% specificities compared with
      each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A
      PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the
      cut-off value for eyes with untreated pressures <or=21 mm Hg, 140 when untreated
      pressure >or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP
      level, and thus represent a glaucoma risk factor. Longitudinal studies are needed
      to prove its prognostic value.

PMID- 17494955
TI  - Familial aggregation of myopia in the Tehran eye study: estimation of the sibling
      and parent offspring recurrence risk ratios.
AB  - AIM: To determine the potential influence of genetic factors on the prevalence of
      myopia in Tehran. METHODS: Of 6497 citizens of Tehran sampled from 160 clusters
      using stratified random cluster sampling, 4565 (70.3%) participated in the study
      and were referred to a clinic for an extensive eye examination and interview.
      These were from 1259 nuclear families with the average size of 3.6. Refraction
      data obtained from 3321 participants aged 16 years and over are presented. Three
      definitions of myopia, as the spherical equivalent of -0.5, -1, and -2 diopters
      or less, were used. Familial aggregation of myopia was evaluated with odds ratios
      and recurrence risk ratios (lambda(R)) using a multiple logistic regression with
      generalised estimating equations (GEE), adjusted for age, sex, height, and
      education. RESULTS: Multivariate analyses showed a strong familial aggregation of
      myopia among siblings (lambda(R) ranging from 2.09 to 3.86) and parent-offspring
      pairs (lambda(R) from 1.82 to 3.81) adjusted for age, sex, height, and education.
      The aggregation increased with higher myopia thresholds and with the use of
      cycloplegic refraction. The odds ratios for spouse pairs were not significantly
      different from 1.0. The association of myopia with sex, height, and education
      (and not age) remained significant in the final GEE2 model. CONCLUSIONS: The
      findings indicate a relatively high degree of familial aggregation of myopia in
      the Tehran population, independent of age, sex, height, and education. This
      residual aggregation may be a result of heredity or of an unmeasured common
      environmental effect.

PMID- 17494956
TI  - Long-term outcome of trans-scleral diode laser cyclophotocoagulation in
      refractory glaucoma.
AB  - BACKGROUND: Long-term outcome and complications of diode laser
      cyclophotocoagulation (DCPC) may be important, since eyes, once treated with
      DCPC, are less likely to be subjected to other types of interventions in the
      further follow-up. METHODS: Retrospective review of 131 eyes of 127 patients
      treated from 2000 through 2004. Success was defined as intraocular pressure (IOP)
      at last visit 6-21 mm Hg; hypotony: IOP </=5 mm Hg. RESULTS: Mean follow-up (FU)
      was 30.1 (SD 16.7) months. Mean number of treatment sessions per eye was 1.54,
      89% of the eyes having 1 or 2 sessions; overall re-treatment rate: 38.9%. Mean
      total laser energy delivered per eye: 133.9 (73.7) J; mean energy per treatment
      episode: 86.8 (22.0) J. Eyes with 3 or more treatments (11%) had a significantly
      larger proportion of post-traumatic glaucoma, and patients were significantly
      younger. All eyes had refractory glaucomas on maximal medication, neovascular
      glaucoma (NVG) representing the largest subgroup (61%). IOP decreased from 36.9
      (10.7) mm Hg pretreatment to 15.3 (10.4) mm Hg at the end of FU. Success was
      noted in 69.5% (91 eyes), failure (non-response) in 13%. Hypotony occurred in
      17.6% eyes, of which 74% had NVG. Hypotony developed after mean 19.3 (11.0)
      months, range 6 to 36; with 96% of these eyes having received only 1 or 2
      treatments; delivered energy did not differ from that in the successful eyes.
      CONCLUSIONS: DCPC is an efficient treatment for refractory glaucoma. Hypotony,
      the most common complication, may develop as late as 36 months post-treatment.
      Diagnostic category and age seem to influence the outcome stronger than laser
      protocol and delivered energy.

PMID- 17494957
TI  - Antidiabetic activity of the orally effective vanadyl-poly (gamma-glutamic acid)
      complex in streptozotocin(STZ)-induced type 1 diabetic mice.
AB  - Newly synthesized vanadyl-poly(gamma-glutamic acid) complex (VO-gamma-PGA) with a
      VO(O4) coordination mode was found to have potent antidiabetic activity in
      streptozotocin (STZ)-induced type 1 diabetic mice (STZ-mice), compared with that
      of a solution containing only vanadyl sulfate, VOSO4. This was the first example
      of orally active vanadyl complex of gamma-PGA for treating STZ-mice. To better
      define its efficacy, we examined here the effects of VO-gamma-PGA treatment in
      STZ-mice by oral administration at the dose of 10 mg V/kg body mass for a longer
      period time than our previous study. The improvement in diabetic states in STZ
      mice compared with saline-treated nondiabetic normal Std ddY mice. It was found
      that the elevated blood glucose levels in STZ-mice significantly decreased after
      3 days and sustained the normalized blood glucose level around 180-200 mg/dL (10
      11.1 mM) for the last 14 days, which is close to the blood glucose levels 100-200
      mg/dL (5.6-11.1 mM) in nondiabetic normal Std ddY mice. The improvement in
      diabetes was strongly corelated by the improvement in oral glucose tolerance
      ability, glycosylated hemoglobin (HbA1c) levels and blood pressure, and serum
      parameters. The present results confirmed that VO-gamma-PGA complex is a
      promising, orally active insulin-mimetic agent to treat type 1 diabetic mice.

PMID- 17494958
TI  - Microbial leakage of Gutta-Percha and Resilon root canal filling material: a
      comparative study using a new homogeneous assay for sequence detection.
AB  - The sealing ability of gutta-percha/sealer root canal filling was compared to a
      new thermoplastic synthetic polymer-based obturation material (Resilon), using a
      microleakage model and a new sequence detection assay One Cut Event AmplificatioN
      (OCEAN). Eighty-eight extracted human teeth, shaped with K-Files and the ProTaper
      Technique, were randomly assigned to four groups (n = 22) and obturated in the
      apical 5 mm. Group R were obturated with the Resilon/Epiphany technique; group GP
      were obturated with gutta-percha and Zinc oxide eugenoe sealer; group RCH and
      GPCH received calcium hydroxide intracanal medication before being obturated.
      Sterilized specimens were inoculated with Enterococcus faecalis and incubated in
      sterile medium for 47 days. DNA extracted from the specimens was amplified by PCR
      and then identified by the OCEAN technique. Samples obturated with Resilon root
      canal filling material showed a greater number of microleakage events than the
      other groups (p = 0.036). Calcium hydroxide medication did not have a relevant
      impact on the quality of the apical seal (p = 0.044).

PMID- 17494960
TI  - A clinical report of bone regeneration in maxillofacial surgery using bonelike
      synthetic bone graft.
AB  - The objective of this study is to evaluate the osteoconductivity and bioactivity
      of the Bonelike graft in repairing surgical cystic bone defects. Bonelike is
      implanted in 11 patients, aged between 24 and 53 years with a mean age of 36
      years, consisting of 5 men and 6 women. According to the standard follow up
      protocols, radiological examinations are performed and Bonelike/bone retrieved
      samples have been analyzed histologically using non-decalcified sections obtained
      perpendicular to bone length axis. Radiographic examination and histological
      results clearly demonstrate an extensive new bone formation apposed on Bonelike
      granules with a significant degree of maturation. These clinical applications in
      maxillary bone defects indicate perfect bone bonding between new bone formed and
      Bonelike granules, along with partial surface biodegradation. This quick and
      effective osteoconductive response from Bonelike may reduce the time needed to
      reconstruct the bone defected area of patients.

PMID- 17494961
TI  - Preparation and properties of poly(lactide-co-glycolide) (PLGA)/ nano
      hydroxyapatite (NHA) scaffolds by thermally induced phase separation and rabbit
      MSCs culture on scaffolds.
AB  - Biodegradable polymer/bioceramic composites scaffold can overcome the limitation
      of conventional ceramic bone substitutes such as brittleness and difficulty in
      shaping. To better mimic the mineral component and the microstructure of natural
      bone, novel nano-hydroxyapatite (NHA)/polymer composite scaffolds with high
      porosity and well-controlled pore architectures as well as high exposure of the
      bioactive ceramics to the scaffold surface is developed for efficient bone tissue
      engineering. In this article, regular and highly interconnected porous
      poly(lactide-co-glycolide) (PLGA)/NHA scaffolds are fabricated by thermally
      induced phase separation technique. The effects of solvent composition, polymer
      concentration, coarsening temperature, and coarsening time as well as NHA content
      on the micro-morphology, mechanical properties of the PLGA/NHA scaffolds are
      investigated. The results show that pore size of the PLGA/NHA scaffolds decrease
      with the increase of PLGA concentration and NHA content. The introduction of NHA
      greatly increase the mechanical properties and water absorption ability which
      greatly increase with the increase of NHA content. Mesenchymal stem cells are
      seeded and cultured in three-dimensional (3D) PLGA/NHA scaffolds to fabricate in
      vitro tissue engineering bone, which is investigated by adhesion rate, cell
      morphology, cell numbers, and alkaline phosphatase assay. The results display
      that the PLGA/NHA scaffolds exhibit significantly higher cell growth, alkaline
      phosphatase activity than PLGA scaffolds, especially the PLGA/NHA scaffolds with
      10 wt.% NHA. The results suggest that the newly developed PLGA/NHA composite
      scaffolds may serve as an excellent 3D substrate for cell attachment and
      migration in bone tissue engineering.

PMID- 17494962
TI  - Three-dimensional cell growth on structures fabricated from ORMOCER by two-photon
      polymerization technique.
AB  - Two-photon polymerization technique was applied to generate three-dimensional
      (3D) scaffold-like structures using the photosensitive organic-inorganic hybrid
      polymer ORMOCER. The structures were studied with respect to potential
      applications as scaffold for tissue engineering. Cell counting and comet assay,
      respectively, demonstrated that doubling time and DNA strand breaks of CHO cells,
      GFSHR-17 granulosa cells, GM-7373 endothelial cells, and SH-SY5Y neuroblastoma
      cells were not affected by ORMOCER. ORMOCER related alteration of formation of
      tissue specific cell-to-cell adhesions like gap junctions was ruled out by double
      whole-cell patch-clamp technique. Additionally, growth of cells on the vertical
      surfaces of 3D structures composed of ORMOCER is shown.

PMID- 17494964
TI  - An initial evaluation of gellan gum as a material for tissue engineering
      applications.
AB  - Alpha-modified minimum essential medium (alphaMEM) has been found to cross-link a
      1% gellan gum solution, resulting in the formation of a self-supporting hydrogel
      in 1:1 and 5:1 ratios of polysaccharide: alphaMEM. Rheological data from
      temperature sweeps confirm that in addition to orders of magnitude differences in
      G' between 1% gellan and 1% gellan with alphaMEM, there is also a 20 degrees C
      increase in the temperature at which the onset of gelation takes place when
      alphaMEM is present. Frequency sweeps confirm the formation of a true gel;
      mechanical spectra for mixtures of gellan and alphaMEM clearly demonstrate G' to
      be independent of frequency. It is possible to immobilize cells within a three
      dimensional (3D) gellan matrix that remain viable for up to 21 days in culture by
      adding a suspension of rat bone marrow cells (rBMC) in alphaMEM to 1% gellan
      solution. This extremely simple approach to cell immobilization within 3D
      constructs, made possible by the fact that gellan solutions cross-link in the
      presence of millimolar concentrations of cations, poses a very low risk to a cell
      population immobilized within a gellan matrix and thus indicates the potential of
      gellan for use as a tissue engineering scaffold.

PMID- 17494965
TI  - Preparation and characterization of cationic chitosan-modified poly(D,L-lactide
      co-glycolide) copolymer nanospheres as DNA carriers.
AB  - Chitosan (CS)-modified poly(D,L-lactide-co-glycolide) (PLGA/CS) nanoparticles
      with cationic surface were prepared by means of emulsion-solvent evaporation
      technique using polyviny alcohol and chitosan as costabilizers. The preparation
      conditions of the cationic nanoparticles were optimized by orthogonal factorial
      design, and the influences of the experiment variables such as polymer
      concentration, the molecular weight of chitosan, etc., on the size and zeta
      potential of the nanoparticles were evaluated. It was shown that the diameter of
      the PLGA/CS nanoparticles can be controlled in the range of 150-200 nm as
      determined by dynamic light scattering with the optimized conditions. The zeta
      potential of PLGA/CS nanoparticles increased with increasing the concentration of
      CS (C(CS)) or decreasing the pH, it was up to 55 mV when C(CS) was 3 mg/mL at pH
      4 and inversed around pH 8. The optimization conditions for fabricating the
      relatively small diameter and high zeta potential cationic nanoparticles were
      C(CS) 3 mg/mL, C(PLGA) 10 mg/mL, and the volume ratio of organic solution to
      aqueous medium 1/4. X-ray photo electron spectroscopy and fluorescence inverted
      microscope observations approved that CS molecules were adsorbed on the surface
      of PLGA nanoparticles, DNA-condensing ability of the PLGA/CS nanoparticles and
      cell transfection efficiency of the nanoparticle-DNA complexes were estimated by
      gel electrophoresis and transfection experiment to 293FT cell, respectively.

PMID- 17494966
TI  - HRP-loaded bioresorbable microspheres: effect of copolymer composition and
      molecular weight on microstructure and release profile.
AB  - Poly(DL-lactic-co-glycolic acid) microspheres are prepared using a double
      emulsion technique and are loaded with the model enzyme horseradish peroxidase
      (HRP). These microspheres can be used alone or as coatings for bioresorbable
      fibers that may be used as scaffolds for tissue regeneration applications. The
      present study focuses on the effect of the copolymer's composition and initial
      molecular weight on the microsphere structure, encapsulation efficiency, and
      cumulative protein release for 12 weeks. The release profiles generally exhibits
      an initial burst effect accompanied by slow release over an extended period of
      time, during which diffusion rather than degradation controlled HRP release from
      these structures. An increase in the initial molecular weight or in the
      copolymer's lactic acid content results in larger microspheres with smoother
      surfaces, and a decrease in the burst release and in the total HRP release.
      Molecular weight is found to have a stronger effect than copolymer composition.
      We demonstrate that it is possible to obtain versatile release profiles, which
      can be tailored for specific applications by choosing the right initial molecular
      weight and copolymer composition.

PMID- 17494967
TI  - Bone formation on the apatite-coated zirconia porous scaffolds within a rabbit
      calvarial defect.
AB  - Previously, a strong and bioactive ceramic scaffold consisting of a porous
      zirconia body coated with apatite double layers (fluorapatite (FA) as an inner
      layer and hydroxyapatite (HA) as an outer layer) was successfully fabricated. In
      this contribution, the authors investigate the in vivo performance of the
      engineered bioceramic scaffolds using a rabbit calvarial defect model. In
      particular, the porosity and pore size of the scaffolds are varied in order to
      observe the geometrical effects of the scaffolds on their bone formation
      behaviors. The scaffolds supported on a zirconia framework can be produced with
      an extremely high porosity (approximately 84-87%), while retaining excellent
      compressive strength (approximately 7-8 MPa), which has been unachievable in the
      case of pure apatite scaffolds (approximately 74% porosity with approximately 2
      MPa strength). The experimental groups used in this study include three types of
      zirconia scaffolds coated with apatite; high porosity (approximately 87%) with
      large pore size (approximately 500- 700 microm): AZ-HL, high porosity
      (approximately 84%) with small pore size (approximately 150-200 microm): AZ-HS,
      and low porosity (approximately 75%) with large pore size (approximately 500-700
      microm): AZ-LL, as well as one type of HA porous scaffold: low porosity
      (approximately 74%) with a large pore size (approximately 500-700 microm) for the
      purpose of comparison. The scaffolds prepared with dimensions of approximately 10
      mm (diameter) x 1.2 mm (thickness) are grafted in rabbit calvaria defects. The
      histological sections are made at 4 and 12 weeks after surgery and
      immunohistochemical analyses are performed on the samples. All of the specimens
      show a good healing response without adverse tissue reactions. Good healing is
      shown at 4 weeks post-surgery with the ingrowth of new bone into the macropore
      channels of the scaffolds. The newly formed bone amounts to approximately 19.9
      24.2% of the initial defect area, depending on the scaffold type, but there is no
      statistical significance between the scaffold groups. However, the defects
      without the scaffolds (control group) show a significantly lower bone formation
      ratio (approximately 4.3%). At twelve weeks after surgery, the extent of new bone
      formation is more pronounced in all of the scaffold groups. All of the scaffold
      groups show significantly higher bone formation ratios (26.7-46.9%) with respect
      to the control without the graft. In the comparison between the scaffold groups,
      those with high porosities (AZ-HL and AZ-HS) exhibit significantly higher bone
      formation as compared to the scaffold with low porosity (AZ-LL). Based on the
      present in vivo test performed within a rabbit calvaria defect model, it is
      concluded that the apatite-coated zirconia scaffolds show good bone forming
      ability and are considered to be a promising scaffolding material for bone
      regeneration since they possess a high level of both mechanical and biological
      properties.

PMID- 17494968
TI  - C3A cell behaviors on micropatterned chitosan collagen gelatin membranes.
AB  - The influence of the properties and surface micropatterning of chitosan-collagen
      gelatin (CCG) blended membranes on C3A cell's activities has been investigated.
      It is aimed to guide the cell growth and improve the growth rate in vitro for the
      application in tissue engineering. Masters with micropatterns are prepared on
      stainless steel plates by photolithography. The CCG membranes with surface
      micropatterns are then fabricated by soft lithography and dry-wet phase inversion
      techniques. The morphology and metabolic activity of cultured C3A cells on the
      membranes are recorded. When the C3A cells are seeded on the membranes with
      micropattern spacing of 200 microm width and 80 microm depth, they adhere and
      aggregate in the groove of the membranes in a few minutes. The aggregated cells
      migrate up to the surface of the ridge later. This phenomenon, however, is not
      found on membranes with a micropattern spacing of 500 microm width. In addition,
      it is demonstrated that the cells on the CCG membranes with micropatterns have
      higher metabolism and growth rates than those on the flat CCG membranes and on T
      flask discs. Micropatterning on the membrane surface can affect the distribution
      of cells and the communication among cells, and results in a difference in cell
      adhesion, morphology, mobility, and growth activity.

PMID- 17494969
TI  - A global comparison regarding patient access to cancer drugs.

PMID- 17494978
TI  - Anthropometric approximation of body weight in unresponsive stroke patients.
AB  - BACKGROUND AND PURPOSE: Thrombolysis of acute ischaemic stroke is based strictly
      on body weight to ensure efficacy and to prevent bleeding complications. Many
      candidate stroke patients are unable to communicate their body weight, and there
      is often neither the means nor the time to weigh the patient. Instead, weight is
      estimated visually by the attending physician, but this is known to be
      inaccurate. METHODS: Based on a large general population sample of nearly 7000
      subjects, we constructed approximation formulae for estimating body weight from
      simple anthropometric measurements (body height, and waist and hip
      circumference). These formulae were validated in a sample of 178 consecutive
      inpatients admitted to our stroke unit, and their accuracy was compared with the
      best visual estimation of two experienced physicians. RESULTS: The simplest
      formula gave the most accurate approximation (mean absolute difference 3.1 (2.6)
      kg), which was considerably better than the best visual estimation (physician 1:
      6.5 (5.2) kg; physician 2: 7.4 (5.7) kg). It reduced the proportion of weight
      approximations mismatched by >10% from 31.5% and 40.4% (physicians 1 and 2,
      respectively) to 6.2% (anthropometric approximation). Only the patient's own
      estimation was more accurate (mean absolute difference 2.7 (2.4) kg).
      CONCLUSIONS: By using an approximation formula based on simple anthropometric
      measurements (body height, and waist and hip circumference), it is possible to
      obtain a quick and accurate approximation of body weight. In situations where the
      exact weight of unresponsive patients cannot be ascertained quickly, we recommend
      using this approximation method rather than visual estimation.

PMID- 17494979
TI  - Idiopathic chronic inflammatory demyelinating polyneuropathy: an epidemiological
      study in Italy.
AB  - AIM: The clinical and epidemiological characteristics of chronic inflammatory
      demyelinating polyneuropathy (CIDP) in an Italian population were assessed.
      SUBJECTS AND METHODS: All subjects with a diagnosis of demyelinating neuropathy
      after 1990 in Piemonte and Valle d'Aosta (4,334,225 inhabitants) were considered.
      The diagnosis of CIDP was based on the research criteria of the American Academy
      of Neurology. 165 of 294 patients met the diagnostic criteria. RESULTS: The crude
      prevalence rate was 3.58/100,000 population (95% CI 3.02 to 4.20). At the
      prevalence day, 76 (49.0%) cases had definite, 67 (43.2%) probable and 12 (7.7%)
      possible CIDP; disability was mild in 105 (67.7%) cases, moderate in 32 (20.6%)
      and severe in 18 (11.6%). The course was remitting-relapsing in 40 cases (25.8%),
      chronic progressive in 96 (61.9%) and monophasic in 19 (12.3%). Considering the
      95 patients whose disorder presented in the period 1995-2001, the mean annual
      crude incidence rate was 0.36/100,000 population (95% CI 0.29 to 0.44), with a
      male to female ratio of 2.3:1. 14 cases were affected by diabetes mellitus. In
      multivariate analysis, factors related to severe disability at the prevalence day
      were: age >60 years; failure of immunomodulating therapies at the time of
      diagnosis; worse disability at nadir; and chronic course. CONCLUSION: Incidence
      and prevalence rates of CIDP in Italy were higher than those observed in most
      previous studies. At the prevalence day, more than 80% of cases had a mild or
      moderate disability, indicating either a good response to immunomodulating
      therapy or a tendency of CIDP to have a mild course in most cases.

PMID- 17494980
TI  - Neutron measurements around storage casks containing spent fuel and vitrified
      high-level radioactive waste at ZWILAG.
AB  - Spectrometric and dosimetric measurements were made around a cask containing
      spent fuel and a cask containing high-level radioactive waste at the Swiss
      intermediate waste and spent fuel storage facility. A Bonner sphere spectrometer,
      an LB 6411 neutron monitor and an Automess Szintomat 6134A were used to
      characterise the n-gamma fields at several locations around the two casks. The
      results of these measurements show that the neutron fluence spectra around the
      cask containing radioactive waste are harder and higher in intensity than those
      measured in the vicinity of the spent fuel cask. The ambient dose equivalents
      measured with the LB 6411 neutron monitor are in good agreement with those
      obtained using the Bonner spheres, except for locations with soft neutron spectra
      where the monitor overestimates the neutron ambient dose equivalent by almost
      50%.

PMID- 17494981
TI  - Local diagnostic reference levels for some common diagnostic X-ray examinations
      in Tehran county of Iran.
AB  - Various researchers who have carried out national and international surveys have
      reported wide variations in patient dose arising from specific X-ray
      examinations. This study was carried out as a part of a comprehensive project to
      establish national diagnostic reference level (NDRL), for the first time, in
      Iran. Seven most common X-ray examinations in 11 projections were included.
      Thermo luminescence dosimeters (TLD-100) were used to measure entrance surface
      doses (ESDs). The study group consisted of 535 patients who were referred for X
      ray examinations to 12 randomly selected public hospitals in Tehran County.
      Minimum, median, mean, maximum, first and third quartile values of ESDs are
      reported. Our results are evident that mean dose values of patients undertaking a
      specific examination are widely different in various hospitals. Wide dose
      differences may emerge from complex causes, but in general, low peak kilovoltage
      and high milli Amperes are associated with higher doses. The results of this work
      together with further data expected to emerge from the work in progress will
      provide a useful base to establish Iran's DRLs.

PMID- 17494982
TI  - Electromagnetic field spectral evaluation problems in exposure assessment.
AB  - Electromagnetic fields have become an omnipresent factor in our daily
      environment. It has become common that the exposure situations are characterised
      by a cocktail of spectral contributions from different sources, while exposures
      to single frequencies are rare. Thirty-two different types of drilling machines
      were analysed. Even similar devices exhibited large variations of emission levels
      up to two orders of magnitudes. It was found that emissions are not negligible
      and could be close or even above reference levels. Already single spectral peaks
      of magnetic emissions may considerably exceed reference levels, and excess can
      reach even the 90-fold when evaluating the entire spectrum. It is shown that
      approaches to assess complex frequency spectra as proposed by the International
      Commission on Non-Ionising Radiation Protection or defined in compliance
      standards issued by CENELEC or IEC lead to contradictory conclusions on
      conformity or non-conformity. There is an urgent need to clarify this
      discrepancy.

PMID- 17494983
TI  - Parenting: a glut of information.

PMID- 17494984
TI  - 'Childhood': are reports of its death greatly exaggerated?
AB  - What is happening to our children's childhoods? Is childhood itself disappearing
      as children become increasingly 'adultified' and commodified and as the lives and
      worlds of children's experiences seem to shrink in the name of protection and
      safety? Are contemporary concerns justified about children becoming less active
      and more comfortable playing Gameboys rather than games and exploring 'Sim City'
      rather than their own real one? Or, are these simply adult 'moral panics' about
      childhood based on little more than nostalgia for a mythical childhood suffused
      with innocence and happiness? This article explores some of the current concerns
      regarding the changing state of childhood and links these to some of our current
      child health and well-being concerns. It concludes by suggesting some small-scale
      'local' initiatives that parents and adults could support relatively easily,
      which would help to enrich childhood.

PMID- 17494985
TI  - Children's attitudes and behavioural intentions towards a peer with symptoms of
      ADHD: does the addition of a diagnostic label make a difference?
AB  - This article explores the impact of diagnostic/psychiatric labelling on the
      attitudes and behavioural intentions of school-aged children towards a
      hypothetical peer presented with symptoms of attention deficit hyperactivity
      disorder (ADHD). A sample of 120 children aged 11-12 years read one of three
      vignettes describing the behaviour of a gender-neutral, same-age peer presenting
      with symptoms of ADHD. The participants completed self-report measures of
      attitudes and behavioural intentions after reading the respective vignettes. The
      majority of participants perceived the vignette character as being male and the
      attitude held towards him was predominately negative. Significant positive
      relationships were found between attitudes and children's willingness to engage
      in social, academic and physical activities. Diagnostic/psychiatric labelling had
      no additional influence upon attitudes or behavioural intentions. Children's
      negative attitude towards peers with symptoms of ADHD, given its association with
      friendship choice, is an important target for change in reducing stigma.

PMID- 17494986
TI  - Gender differences and similarities in the experience of parenting a child with a
      health problem: current state of knowledge.
AB  - The birth of a child is a transitional situation that triggers stress in the
      family and each person has to use adjustment strategies allowing them to
      reposition gradually in relation to themselves and other members of the family,
      and to make space for the new arrival. When the child has a health problem, the
      stress on the parents is correspondingly greater. Research shows that fathers and
      mothers of a child with a health problem experience this ordeal differently. This
      article reports on the current state of knowledge about the experience of fathers
      and mothers of a child with a health problem, and suggests new directions for
      research to provide a fuller understanding of their experience.

PMID- 17494987
TI  - Disease-related stress in parents of children who are overweight: relations with
      parental anxiety and childhood psychosocial functioning.
AB  - The psychometric properties of the Pediatric Inventory for Parents, a measure of
      chronic disease-related parental stress, were examined in a sample of 72 children
      and adolescents who are overweight. The correlations between disease-related
      parental stress and general parenting stress, parental and child anxiety and
      children's behavioral and psychological maladjustment were examined. The results
      demonstrated excellent internal consistency and modest correlations with a
      measure of general parenting stress. Significant and positive relations of medium
      to large effect sizes between disease-related parenting stress and internalizing
      and externalizing maladjustment were found. Internalizing and externalizing
      behavior moderated the relations between disease-related parenting stress and
      parental distress. Recommendations for use of the Pediatric Inventory for Parents
      in clinical settings and future research directions are discussed.

PMID- 17494988
TI  - Parents with chronic pain: are children equally affected by fathers as mothers in
      pain? A pilot study.
AB  - This study compared the psychological and physical functioning of 12 children in
      each of three groups: mothers with chronic pain, fathers with chronic pain and a
      control, pain-free parents. Parents completed a number of questionnaires
      including the RAND-36 Health Status Inventory, a child health scale and the Child
      Behavior Checklist. Children completed the Revised Child Manifest Anxiety Scale
      and a scale measuring pain and sickness behaviour. Children of mothers with
      chronic pain reported the most physical and psychological problems, followed by
      children of fathers with chronic pain and children from the control group. Pain
      reports between children and parents with chronic pain were significantly
      correlated, suggesting support for a familial pain model. Social learning may
      explain the concordance between parent and child health in families experiencing
      parental chronic pain.

PMID- 17494989
TI  - Home dressing removal following hypospadias repair.
AB  - Hypospadias is a common congenital abnormality that is increasing in incidence.
      There are many articles describing different surgical techniques and the merits
      of different dressings following hypospadias surgery. This article describes
      postoperative nursing management in collaboration with each family following
      surgery. Listening to the wishes of parents identified ways in which improvements
      could be made to the patient journey. The involvement of parents in decision
      making has been at the heart of developments in the care of boys who have
      hypospadias repair. A review of nursing care in combination with partnerships
      with paediatric community nursing teams has enabled the additional benefit of
      developing a home dressing removal service following hypospadias repair.

PMID- 17494990
TI  - Hazardous drinking in New Zealand sportspeople: level of sporting participation
      and drinking motives.
AB  - AIMS: To examine the relationship between athlete drinking motives and hazardous
      drinking across differing levels of sporting participation (club vs elite
      provincial vs elite-international). METHODS: Data from 1214 New Zealand
      sportspeople was collected. We assessed hazardous drinking with the WHO's AUDIT
      questionnaire and sportspeople's psychosocial reasons for drinking with the ADS.
      Level of sporting participation (club/social, provincial/state, or
      international/olympic level) was also assessed. RESULTS: Hazardous drinking
      behaviours differed across levels of sporting participation, with elite
      provincial sportspeople showing the highest level of hazardous drinking,
      club/social sportspeople the next highest and elite-international sportspeople
      the lowest. Sportspeople who placed a greater emphasis on drinking as a reward
      for participating in their sports tended to display more hazardous drinking
      behaviours, but other ADS motives differed over level of sporting participation.
      Elite-provincial sportspeople and elite-international sportspeople placed more
      emphasis on drinking as a way to cope with the stresses of participating in their
      sports. A relationship between team/group motives and AUDIT scores was fully
      mediated by positive reinforcement motives, and partially mediated by stress
      related coping motives. CONCLUSIONS: These findings have implications for alcohol
      education programs targeted at sportspeople and sport administration, and may
      help improve the efficacy and focus of intervention programs.

PMID- 17494991
TI  - Characterization of cyclin L1 as an immobile component of the splicing factor
      compartment.
AB  - Cyclin L1 and cyclin L2 are two closely related members of the cyclin family that
      contain C-terminal arginine- and serine-rich (RS) domains and are localized in
      the splicing factor compartment (nuclear speckles). Here we applied
      photobleaching techniques to show that a green fluorescent protein (GFP) fusion
      protein of cyclin L1, in contrast to cyclin L2, was not mobile within the nucleus
      of living COS7 cells. The objectives of this study were to 1) characterize the
      intranuclear localization and mobility properties of cyclin L1 in different
      cellular states, and 2) dissect the structural elements required for
      immobilization of cyclin L1. Transcriptional arrest by actinomycin D caused
      accumulation of GFP-cyclin L2 in rounded and enlarged nuclear speckles but did
      not affect the subnuclear pattern of distribution of GFP-cyclin L1. Although
      immobile in most phases of the cell cycle, GFP-cyclin L1 was diffusely
      distributed and highly mobile in the cytoplasm of metaphase cells. By analysis of
      a series of chimeras, deletion constructs, and a point mutant, a segment within
      the RS domain of cyclin L1 was identified to be necessary for the immobility of
      the protein in nuclear speckles. This study provides the first characterization
      of an immobile component of nuclear speckles.

PMID- 17494992
TI  - Human pancreatic islet endothelial cells express coxsackievirus and adenovirus
      receptor and are activated by coxsackie B virus infection.
AB  - Enteroviruses, such as the coxsackievirus (CV) group, have been linked to the
      induction of inflammatory and autoimmune diseases. Virus tropism and tissue
      access are modulated by endothelial cells. To examine the susceptibility of
      microvascular endothelial cells (MECs) derived from pancreatic islets to
      infection with CV group B (CVB), purified cultured human islet MECs were infected
      with CVB-4 strain, and the immunological phenotype of the infected cells was
      analyzed. CVB-4 persistently infected the islet MECs, which expressed the CV
      receptors human coxsackievirus and adenovirus receptor (HCAR) and decay
      accelerating factor (DAF) and maintained EC characteristics, without overt
      cytopathic effects. CVB-4 infection transiently up-regulated expression of the
      adhesion molecules ICAM-1 and VCAM-1 and increased production of the
      proinflammatory cytokines IL-1beta and IL-6, and chemokines IL-8 and
      lymphotactin, as well as IFN-alpha. Mononuclear cell adhesion to CVB infected
      monolayers was increased, compared to uninfected monolayers. Moreover, infection
      up-regulated the viral receptors HCAR and DAF and coreceptor alpha(v)beta3
      integrin on islet MECs, while down-regulating expression of HCAR on human aortic
      endothelial cells, indicating potential tissue-specific influence on the
      pathological outcome of infection. These results provide evidence that islet MECs
      are natural targets and reservoirs for persistent CVB infection resulting in
      acute endothelial cell activation by virus, which may contribute to selective
      recruitment of subsets of leukocytes during inflammatory immune responses, such
      as insulitis in type 1 diabetes.

PMID- 17494993
TI  - Bcl-2 overexpression delays caspase-3 activation and rescues cerebellar
      degeneration in prion-deficient mice that overexpress amino-terminally truncated
      prion.
AB  - Prnp knockout mice that overexpress an amino-truncated form of PrPc (deltaPrP)
      are ataxic and display cerebellar cell loss and premature death. Studies on the
      molecular and intracellular events that trigger cell death in these mutants may
      contribute to elucidate the functions of PrPc and to the design of treatments for
      prion disease. Here we examined the effects of Bcl-2 overexpression in neurons on
      the development of the neurological syndrome and cerebellar pathology of
      deltaPrP. We show that deltaPrP overexpression activates the stress-associated
      kinases ERK1-2 in reactive astroglia, p38 and the phosphorylation of p53, which
      leads to the death of cerebellar neurons in mutant mice. We found that the
      expression of deltaPrP in cell lines expressing very low levels of PrPc strongly
      induces the activation of apoptotic pathways, thereby leading to caspase-3
      activation and cell death, which can be prevented by coexpressing Bcl-2. Finally,
      we corroborate in vivo that neuronal-directed Bcl-2 overexpression in deltaPrP
      mice (deltaPrP Bcl-2) markedly reduces caspase-3 activation, glial activation,
      and neuronal cell death in cerebellum by improving locomotor deficits and life
      expectancy.

PMID- 17494994
TI  - Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization.
AB  - Memapsin 2 (beta-secretase, BACE1) is the protease that initiates cleavage of
      beta-amyloid precursor protein leading to the production of amyloid-beta (Abeta)
      and the onset of Alzheimer's disease (AD). Reducing Abeta by targeting memapsin 2
      is a major strategy in developing new AD therapy. Here, in a proof-of-concept
      study, we show that immunization of transgenic AD mice (Tg2576) with memapsin 2
      resulted in Abeta reduction and cognitive improvement. To study the basis of this
      therapy, we demonstrated that anti-memapsin 2 (anti-M2) antibodies were rapidly
      internalized and reduced Abeta production in cultured cells. These antibodies
      also effectively crossed the blood-brain barrier to reach the brain. Two- and 10
      month Tg2576 mice were immunized and monitored over 10 and 6 months,
      respectively. We observed a significant decrease of plasma and brain Abeta40 and
      Abeta42 (approximately 35%) in the immunized mice as compared to controls.
      Immunized mice also showed better cognitive performance than controls in both
      cohorts. Brain histological analyses found no evidence of T
      cell/microglia/astrocyte activation in the immunized mice, suggesting the absence
      of inflammatory responses. These results suggest that memapsin 2 immunization in
      Tg2576 was effective in reducing Abeta production and improving cognitive
      function and that the current approach warrants further investigation as a
      therapy for AD.

PMID- 17494995
TI  - The 69 kDa Escherichia coli maltodextrin glucosidase does not get encapsulated
      underneath GroES and folds through trans mechanism during GroEL/GroES-assisted
      folding.
AB  - Escherichia coli chaperonin GroEL and GroES assist in folding of a wide variety
      of substrate proteins in the molecular mass range of approximately 50 kDa, using
      cis mechanism, but limited information is available on how they assist in folding
      of larger proteins. Considering that the central cavity of GroEL can accommodate
      a non-native protein of approximately 60 kDa, it is important to study the GroEL
      GroES-assisted folding of substrate proteins that are large enough for cis
      encapsulation. In this study, we have reported the mechanism of GroEL/GroES
      assisted in vivo and in vitro folding of a 69 kDa monomeric E. coli protein
      maltodextrin glucosidase (MalZ). Coexpression of GroEL and GroES in E. coli
      causes a 2-fold enhancement of exogenous MalZ activity in vivo. In vitro, GroEL
      and GroES in the presence of ATP give rise to a 7-fold enhancement in MalZ
      refolding. Neither GroEL nor single ring GroEL (SR1) in the presence or absence
      of ATP could enhance the in vitro folding of MalZ. GroES could not encapsulate
      GroEL-bound MalZ. All these experimental findings suggested that GroEL/GroES
      assisted folding of MalZ followed trans mechanism, whereas denatured MalZ and
      GroES bound to the opposite rings of a GroEL molecule.

PMID- 17494996
TI  - Mineralocorticoid receptor blockade attenuates chronic overexpression of the
      renin-angiotensin-aldosterone system stimulation of reduced nicotinamide adenine
      dinucleotide phosphate oxidase and cardiac remodeling.
AB  - The renin-angiotensin-aldosterone system contributes to cardiac remodeling,
      hypertrophy, and left ventricular dysfunction. Angiotensin II and aldosterone
      (corticosterone in rodents) together generate reactive oxygen species (ROS) via
      reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which likely
      facilitate this hypertrophy and remodeling. This investigation sought to
      determine whether cardiac oxidative stress and cellular remodeling could be
      attenuated by in vivo mineralocorticoid receptor (MR) blockade in a rodent model
      of the chronically elevated tissue renin-angiotensin-aldosterone system, the
      transgenic TG (mRen2) 27 rat (Ren2). The Ren2 overexpresses the mouse renin
      transgene with resultant hypertension, insulin resistance, proteinuria, and
      cardiovascular damage. Young (6- to 7-wk-old) male Ren2 and age-matched Sprague
      Dawley rats were treated with spironolactone or placebo for 3 wk. Heart tissue
      ROS, immunohistochemical analysis of 3-nitrotyrosine, and NADPH oxidase (NOX)
      subunits (gp91(phox) recently renamed NOX2, p22(phox), Rac1, NOX1, and NOX4) were
      measured. Structural changes were assessed with cine-magnetic resonance imaging,
      transmission electron microscopy, and light microscopy. Significant increases in
      Ren2 septal wall thickness (cine-magnetic resonance imaging) were accompanied by
      perivascular fibrosis, increased mitochondria, and other ultrastructural changes
      visible by light microscopy and transmission electron microscopy. Although there
      was no significant reduction in systolic blood pressure, significant improvements
      were seen with MR blockade on ROS formation and NOX subunits (each P < 0.05).
      Collectively, these data suggest that MR blockade, independent of systolic blood
      pressure reduction, improves cardiac oxidative stress-induced structural and
      functional changes, which are driven, in part, by angiotensin type 1 receptor
      mediated increases in NOX.

PMID- 17494997
TI  - Fibroblast growth factor-9, a local regulator of ovarian function.
AB  - Fibroblast growth factor 9 (FGF9) is widely expressed in embryos and fetuses and
      has been shown to be involved in male sex determination, testicular cord
      formation, and Sertoli cell differentiation. Given its male gender bias, the
      ovary has not been reported to express FGF9, nor has a role in ovarian function
      been explored. We report here that FGF9 mRNA and protein are present in the rat
      ovary and provide evidence that supports a role for FGF9 in ovarian progesterone
      production. FGF9 mRNA levels as determined by real-time PCR were high in 4-d-old
      rat ovaries, thereafter declining and stabilizing at levels approximately 30% of
      d 4 levels at d 12-25. Levels of FGF9 mRNA in the ovary were significantly higher
      than that present in adult testis, at all ages studied. The FGF9 receptors FGFR2
      and FGFR3 mRNAs were present in postnatal and immature rat ovary and appeared to
      be constitutively expressed. FGF9 protein was localized to theca, stromal cells,
      and corpora lutea and FGFR2 and FGFR3 proteins to granulosa cells, theca cells,
      oocytes, and corpora lutea, by immunohistochemistry. Follicular differentiation
      induced by gonadotropin treatment reduced the expression of FGF9 mRNA by immature
      rat ovaries, whereas the estrogen-stimulated development of large preantral
      follicles had no significant effect. In vitro, FGF9 stimulated progesterone
      production by granulosa cells beyond that elicited by a maximally stimulating
      dose of FSH. When the granulosa cells were pretreated with FSH to induce LH
      receptors, FGF9 was found not to be as potent as LH in stimulating progesterone
      production, nor did it enhance LH-stimulated production. The combined treatments
      of FSH/FGF9 and FSH/LH, however, were most effective at stimulating progesterone
      production by these differentiated granulosa cells. Analyses of steroidogenic
      regulatory proteins indicate that steroidogenic acute regulatory protein and P450
      side chain cleavage mRNA levels were enhanced by FGF9, providing a mechanism of
      action for the increased progesterone synthesis. In summary, the data are
      consistent with a paracrine role for FGF9 in the ovary.

PMID- 17494998
TI  - Cell membrane structures during exocytosis.
AB  - Exocytosis is a key biological process that controls the neurotransmission and
      release of hormones from cells. In endocrine cells, hormones are packed into
      secretory vesicles and released into the extracellular environment via openings
      in the plasma membrane, a few hundred nanometers wide, which form as a result of
      fusion of the membranes of the granule and cell. The complex processes and
      dynamics that result in the formation of the fusion pore, as well as its
      structure, remain scantly understood. A number of different exocytosis mechanisms
      have been postulated. Furthermore, the possibility exists that several mechanisms
      occur simultaneously. We present here an investigation of the cell membrane
      dynamics during exocytosis in anterior pituitary cells, especially gonadotropes,
      which secrete LH, a hormone central to ovulation. Gonadotrope enrichment was
      achieved using immunolabeled magnetic nanobeads. Three complementary imaging
      techniques were used to realize a fine structure study of the dynamics of the
      exocytosis-like sites occurring during secretion. Living pituitary and
      gonadotrope-enriched cells were imaged with atomic force microscopy, as well as
      cells that had been fixed to obtain better resolution. Atomic force microscopy,
      along with scanning and transmission electron microscopy, studies of these cells
      revealed that there are at least two different site configurations: simple single
      fusion pores and a complex association of pores consisting of a simple primary
      site combined with secondary attachments.

PMID- 17494999
TI  - RFamide peptides inhibit the expression of melanotropin and growth hormone genes
      in the pituitary of an Agnathan, the sea lamprey, Petromyzon marinus.
AB  - Neuropeptides with the Arg-Phe-amide motif at their C termini (RFamide peptides)
      were identified in the brains of several vertebrates, and shown to have important
      physiological roles in neuroendocrine, behavioral, sensory, and autonomic
      functions. The present study identified RFamide peptides, which are teleost
      prolactin-releasing peptide (PrRP) homologs, in the sea lamprey, Petromyzon
      marinus and characterized their effect on the release of pituitary hormones in
      vitro. Two RFamide peptides (RFa-A and RFa-B) were isolated from an acid extract
      of sea lamprey brain, including hypothalamus by Sep-Pak C18 cartridge, affinity
      chromatography using anti-salmon PrRP serum, and reverse-phase HPLC on an ODS
      120T column. Amino acid (aa) sequences and mass spectrometric analyses revealed
      that RFa-A and RFa-B consist of 25 and 20 aa, respectively, and have 75% sequence
      identity within the C-terminal 20 aa. The RFa-B cDNA encoding a preprohormone of
      142 aa was cloned from the lamprey brain, and the deduced aa sequence from
      positions 48-67 was identical to the sequence of RFa-B. However, the
      preprohormone does not include an aa sequence similar to the RFa-A sequence. Cell
      bodies, which were immunoreactive to anti-salmon PrRP serum, were located in the
      periventricular arcuate nucleus, ventral part of the hypothalamus, and
      immunoreactive fibers were abundant from the hypothalamus to the brain. A small
      number of immunoreactive fibers were detected in the dorsal half of the rostral
      pars distalis of the pituitary, close to the GH-producing cells. In addition,
      anti-salmon PrRP immunoreactivities were observed in the pars intermedia,
      corresponding to melanotropin cells. Likewise, signal of RFa-B mRNA was detected
      not only in the brain but also in the pars intermedia. The synthetic RFa-A and -B
      inhibited GH mRNA expression in a dose-dependent fashion in vitro, which is
      comparable to the inhibitory effect of teleost PrRP on GH release. Both RFa-A and
      -B also inhibited the expression of proopiomelanotropin mRNA, but no effects were
      observed in the expression of proopiocortin and gonadotropin beta mRNAs. The
      results indicate that RFamide peptides, which are teleost PrRP homologs, are
      present in the hypothalamus and pituitary of sea lamprey, and may be
      physiologically involved in the inhibition of GH and melanotropin release in the
      sea lamprey pituitary.

PMID- 17495000
TI  - Developmental control of plasma leptin and adipose leptin messenger ribonucleic
      acid in the ovine fetus during late gestation: role of glucocorticoids and
      thyroid hormones.
AB  - In developed countries, the increasing incidence of obesity is a serious health
      problem. Leptin exposure in the perinatal period affects long-term regulation of
      appetite and energy expenditure, but control of leptin production in utero is
      unclear. This study investigated perirenal adipose tissue (PAT) and placental
      leptin expression in ovine fetuses during late gestation and after manipulation
      of plasma glucocorticoid and thyroid hormone concentrations. Between 130 and 144
      d of gestation (term at 145 +/- 2 d), plasma leptin and PAT leptin mRNA levels
      increased in association with increments in plasma cortisol and T(3). Fetal
      adrenalectomy prevented these developmental changes, and exposure of intact 130 d
      fetuses to glucocorticoids, by cortisol infusion or maternal dexamethasone
      treatment, caused premature elevations in plasma leptin and PAT leptin gene
      expression. Fetal thyroidectomy increased plasma leptin and PAT leptin mRNA
      abundance, whereas intravenous T(3) infusion to intact 130 d fetuses had no
      effect on circulating or PAT leptin. Leptin mRNA expression was low in the ovine
      placenta. Therefore, in the sheep fetus, PAT appears to be a primary source of
      leptin in the circulation, and leptin gene expression is regulated by both
      glucocorticoids and thyroid hormones. Developmental changes in circulating and
      PAT leptin may mediate the maturational effects of cortisol in utero and have
      long-term consequences for appetite regulation and the development of obesity.

PMID- 17495001
TI  - Disruption of peripheral leptin signaling in mice results in hyperleptinemia
      without associated metabolic abnormalities.
AB  - Although central leptin signaling appears to play a major role in the regulation
      of food intake and energy metabolism, the physiological role of peripheral leptin
      signaling and its relative contribution to whole-body energy metabolism remain
      unclear. To address this question, we created a mouse model (Cre-Tam mice) with
      an intact leptin receptor in the brain but a near-complete deletion of the
      signaling domain of leptin receptor in liver, adipose tissue, and small intestine
      using a tamoxifen (Tam)-inducible Cre-LoxP system. Cre-Tam mice developed marked
      hyperleptinemia (approximately 4-fold; P < 0.01) associated with 2.3-fold
      increase (P < 0.05) in posttranscriptional production of leptin. Whereas this is
      consistent with the disruption of a negative feedback regulation of leptin
      production in adipose tissue, there were no discernable changes in energy
      balance, thermoregulation, and insulin sensitivity. Hypothalamic levels of
      phosphorylated signal transducer and activator of transcription 3, neuropeptide
      expression, and food intake were not changed despite hyperleptinemia. The
      percentage of plasma-bound leptin was markedly increased (90.1-96 vs. 41.8-74.7%;
      P < 0.05), but plasma-free leptin concentrations remained unaltered in Cre-Tam
      mice. We conclude from these results that 1) the relative contribution to whole
      body energy metabolism from peripheral leptin signaling is insignificant in vivo,
      2) leptin signaling in adipocyte constitutes a distinct short-loop negative
      feedback regulation of leptin production that is independent of tissue metabolic
      status, and 3) perturbation of peripheral leptin signaling alone, although
      increasing leptin production, may not be sufficient to alter the effective plasma
      levels of leptin because of the counter-regulatory increase in the level of
      leptin binding protein(s).

PMID- 17495002
TI  - Sensory stimuli directly acting at the central nervous system regulate gastric
      ghrelin secretion. an ex vivo organ culture study.
AB  - Ghrelin, a novel gastrointestinal hormone involved in GH regulation, has been
      postulated as a relevant orexigenic peptide released by splanchnic tissues.
      Descriptive studies have shown that plasma ghrelin levels increase in states of
      negative energy balance or fasting, while decreasing in obesity and after
      feeding. In the present study, a novel organ-culture model of gastric tissue
      explants obtained from rat donors has been validated for ex vivo experiments.
      Fasting induced gastric ghrelin release as well as ghrelin mRNA expression that
      were reflected in plasma. Interestingly, those changes were fully reverted by 15
      min of refeeding before stomach extraction. Unexpectedly, when animals were
      allowed 15 min before explant extraction to see or smell, but not eat, the food
      (tease feeding), ghrelin secretion was suppressed just like in gastric explants
      from refed animals. This effect was blocked when the animals were subjected to
      surgical vagotomy or treated with atropine sulphate. In conclusion, gastric
      explants were a suitable model for testing ghrelin mechanism of secretion in
      vitro, and they were found to maintain memory of the previously received signals.
      Similar to feeding, tease feeding resulted in suppression of ghrelin discharge by
      explants.

PMID- 17495003
TI  - A new rat model exhibiting both ovarian and metabolic characteristics of
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder
      associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and
      insulin resistance. However, its etiology is unclear, and its management is often
      unsatisfactory or requires a diversified approach. Here, we describe a new rat
      PCOS model, the first to exhibit both ovarian and metabolic characteristics of
      the syndrome. Female rats received the nonaromatizable androgen
      dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous
      administration, beginning before puberty, to activate androgen receptors. Adult
      DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed
      from atretic follicles, and a diminished granulosa layer. They also displayed
      metabolic features, including increased body weight, increased body fat, and
      enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin
      resistance. All letrozole rats were anovulatory and developed polycystic ovaries
      with structural changes strikingly similar to those in human PCOS. Our findings
      suggest that the formation of a "hyperplastic" theca interna reflects the
      inclusion of luteinized granulosa cells in the cyst wall rather than true
      hyperplasia. We conclude that the letrozole model is suitable for studies of the
      ovarian features of human PCOS, while the DHT model is suitable for studies of
      both ovarian and metabolic features of the syndrome.

PMID- 17495004
TI  - Acute and selective inhibition of adipocyte glyceroneogenesis and cytosolic
      phosphoenolpyruvate carboxykinase by interferon gamma.
AB  - Interferon gamma (IFN-gamma) was previously shown to promote fatty acid (FA)
      release from adipose tissue (AT). Net lipolysis is an equilibrium between
      triglyceride breakdown and FA re-esterification. The latter requires activated
      glyceroneogenesis for glycerol-3-phosphate synthesis and increased cytosolic
      phosphoenolpyruvate carboxykinase (PEPCK-C), the key enzyme in this pathway. We
      wondered whether glyceroneogenesis and PEPCK-C would be IFN-gamma targets. We
      injected mice with IFN-gamma, and exposed either AT explants and isolated
      adipocytes from humans and mice or 3T3-F442A adipocytes to IFN-gamma before
      monitoring expression of genes involved in lipid metabolism and the metabolic
      consequences. We show that IFN-gamma induces a large increase in FA release
      without affecting glycerol output and decreases [1-(14)C]-pyruvate incorporation
      into lipids, thus demonstrating that FA re-esterification is reduced due to
      diminished glyceroneogenesis. A series of mRNA encoding proteins involved in FA
      metabolism remained unaffected by IFN-gamma, while that of PEPCK-C was rapidly
      and drastically lowered. IFN-gamma effect opposed that of the beta-agonist
      isoproterenol and of 8-Br-cAMP. In IFN-gamma-treated mice, PEPCK-C gene
      expression was decreased in AT, but not in liver or kidney. Thus, IFN-gamma
      exerts a tissue-specific action in rodents and humans, having glyceroneogenesis
      and the PEPCK-C gene as selective targets to intensify FA release from
      adipocytes.

PMID- 17495005
TI  - Distinct roles for steroidogenic factor 1 and desert hedgehog pathways in fetal
      and adult Leydig cell development.
AB  - Testicular Leydig cells produce testosterone and provide the hormonal environment
      required for male virilization and spermatogenesis. In utero, fetal Leydig cells
      (FLCs) are necessary for the development of the Wolffian duct and male external
      genitalia. Steroidogenic factor 1 (Sf1) is a transcriptional regulator of hormone
      biosynthesis genes, thus serving a central role in the Leydig cell. Desert
      hedgehog (Dhh), a Sertoli cell product, specifies the FLC lineage in the
      primordial gonad through a paracrine signaling mechanism. Postnatally, FLCs are
      replaced in the testis by morphologically distinct adult Leydig cells (ALCs). To
      study a putative interaction between Sf1 and Dhh, we crossed Sf1 heterozygous
      mutant mice with Dhh homozygous null mice to test the function of these two genes
      in vivo. All of the compound Sf1(+/-); Dhh(-/-) mutants failed to masculinize and
      were externally female. However, embryonic gonads contained anastomotic testis
      cords with Sertoli cells and germ cells, indicating that sex reversal was not
      attributable to a fate switch of the early gonad. Instead, external feminization
      was attributable to the absence of differentiated FLCs in XY compound mutant
      mice. ALCs also failed to develop, suggesting either a dependence of ALCs on the
      prenatal establishment of Leydig cell precursors or that Sf1 and Dhh are both
      required for ALC maturation. In summary, this study provides genetic evidence
      that combinatorial expression of the paracrine factor Dhh and nuclear
      transcription factor Sf1 is required for Leydig cell development.

PMID- 17495006
TI  - Pharmacological and physiological characterization of d[Leu4, Lys8]vasopressin,
      the first V1b-selective agonist for rat vasopressin/oxytocin receptors.
AB  - Recently, we synthesized and characterized the first selective V(1b) vasopressin
      (VP)/oxytocin receptor agonist, d[Cha(4)]arginine vasopressin. However, this
      agonist was only selective for the human receptors. We thus decided to design a
      selective V(1b) agonist for the rodent species. We started from previous
      observations showing that modifying [deamino(1),Arg(8)]VP in positions 4 and 8
      altered the rat VP/oxytocin receptor selectivity. We synthesized a series of 13
      [deamino(1),Arg(8)]VP analogs modified in positions 4 and 8. Among them, one
      seemed very promising, d[Leu(4), Lys(8)]VP. In this paper, we describe its
      pharmacological and physiological properties. This analog exhibited a nanomolar
      affinity for the rat, human, and mouse V(1b) VP receptors and a strong V(1b)
      selectivity for the rat species. On AtT20 cells stably transfected with the rat
      V(1b) receptor, d[Leu(4), Lys(8)]VP behaved as a full agonist on both
      phospholipase C and MAPK assays. Additional experiments revealed its ability to
      induce the internalization of enhanced green fluorescent protein-tagged human and
      mouse V(1b) receptors as expected for a full agonist. Additional physiological
      experiments were performed to further confirm the selectivity of this peptide.
      Its antidiuretic, vasopressor, and in vitro oxytocic activities were weak
      compared with those of VP. In contrast, used at low doses, its efficiency to
      stimulate adrenocorticotropin or insulin release from mouse pituitary or perfused
      rat pancreas, respectively, was similar to that obtained with VP. In conclusion,
      d[Leu(4), Lys(8)]VP is the first selective agonist available for the rat V(1b) VP
      receptor. It will allow a better understanding of V(1b) receptor-mediated effects
      in rodents.

PMID- 17495007
TI  - Weaning triggers a decrease in receptor activator of nuclear factor-kappaB ligand
      expression, widespread osteoclast apoptosis, and rapid recovery of bone mass
      after lactation in mice.
AB  - A significant portion of milk calcium comes from the mother's skeleton, and
      lactation is characterized by rapid bone loss. The most remarkable aspect of this
      bone loss is its complete reversibility, and the time after weaning is the most
      rapid period of skeletal anabolism in adults. Despite this, little is known of
      the mechanisms by which the skeleton repairs itself after lactation. We examined
      changes in bone and calcium metabolism defining the transition from bone loss to
      bone recovery at weaning in mice. Bone mass decreases during lactation and
      recovers rapidly after weaning. Lactation causes changes in bone
      microarchitecture, including thinning and perforation of trabecular plates that
      are quickly repaired after weaning. Weaning causes a rapid decline in urinary C
      telopeptide levels and stimulates an increase in circulating levels of
      osteocalcin. Bone histomorphometry documented a significant reduction in the
      numbers of osteoclasts on d 3 after weaning caused by a coordinated wave of
      osteoclast apoptosis beginning 48 h after pup removal. In contrast, osteoblast
      numbers and bone formation rates, which are elevated during lactation, remain so
      3 d after weaning. The cessation of lactation stimulates an increase in
      circulating calcium levels and a reciprocal decrease in PTH levels. Finally,
      weaning is associated with a decrease in levels of receptor activator of nuclear
      factor-kappaB ligand mRNA in bone. In conclusion, during lactation, bone turnover
      is elevated, and bone loss is rapid. Weaning causes selective apoptosis of
      osteoclasts halting bone resorption. The sudden shift in bone turnover favoring
      bone formation subsequently contributes to the rapid recovery of bone mass.

PMID- 17495008
TI  - Three distinct modes of intron dynamics in the evolution of eukaryotes.
AB  - Several contrasting scenarios have been proposed for the origin and evolution of
      spliceosomal introns, a hallmark of eukaryotic genes. A comprehensive
      probabilistic model to obtain a definitive reconstruction of intron evolution was
      developed and applied to 391 sets of conserved genes from 19 eukaryotic species.
      It is inferred that a relatively high intron density was reached early, i.e., the
      last common ancestor of eukaryotes contained >2.15 introns/kilobase, and the last
      common ancestor of multicellular life forms harbored approximately 3.4
      introns/kilobase, a greater intron density than in most of the extant fungi and
      in some animals. The rates of intron gain and intron loss appear to have been
      dropping during the last approximately 1.3 billion years, with the decline in the
      gain rate being much steeper. Eukaryotic lineages exhibit three distinct modes of
      evolution of the intron-exon structure. The primary, balanced mode, apparently,
      operates in all lineages. In this mode, intron gain and loss are strongly and
      positively correlated, in contrast to previous reports on inverse correlation
      between these processes. The second mode involves an elevated rate of intron loss
      and is prevalent in several lineages, such as fungi and insects. The third mode,
      characterized by elevated rate of intron gain, is seen only in deep branches of
      the tree, indicating that bursts of intron invasion occurred at key points in
      eukaryotic evolution, such as the origin of animals. Intron dynamics could depend
      on multiple mechanisms, and in the balanced mode, gain and loss of introns might
      share common mechanistic features.

PMID- 17495009
TI  - Evolutionarily conserved genes preferentially accumulate introns.
AB  - Introns that interrupt eukaryotic protein-coding sequences are generally thought
      to be nonfunctional. However, for reasons still poorly understood, positions of
      many introns are highly conserved in evolution. Previous reconstructions of
      intron gain and loss events during eukaryotic evolution used a variety of
      simplified evolutionary models that yielded contradicting conclusions and are not
      suited to reveal some of the key underlying processes. We combine a comprehensive
      probabilistic model and an extended data set, including 391 conserved genes from
      19 eukaryotes, to uncover previously unnoticed aspects of intron evolution--in
      particular, to assign intron gain and loss rates to individual genes. The rates
      of intron gain and loss in a gene show moderate positive correlation. A gene's
      intron gain rate shows a highly significant negative correlation with the coding
      sequence evolution rate; intron loss rate also significantly, but positively,
      correlates with the sequence evolution rate. Correlations of the opposite signs,
      albeit less significant ones, are observed between intron gain and loss rates and
      gene expression level. It is proposed that intron evolution includes a neutral
      component, which is manifest in the positive correlation between the gain and
      loss rates and a selection-driven component as reflected in the links between
      intron gain and loss and sequence evolution. The increased intron gain and
      decreased intron loss in evolutionarily conserved genes indicate that intron
      insertion often might be adaptive, whereas some of the intron losses might be
      deleterious. This apparent functional importance of introns is likely to be due,
      at least in part, to their multiple effects on gene expression.

PMID- 17495010
TI  - An analysis of the gene complement of a marsupial, Monodelphis domestica:
      evolution of lineage-specific genes and giant chromosomes.
AB  - The newly sequenced genome of Monodelphis domestica not only provides the out
      group necessary to better understand our own eutherian lineage, but it enables
      insights into the innovative biology of metatherians. Here, we compare
      Monodelphis with Homo sequences from alignments of single nucleotides, genes, and
      whole chromosomes. Using PhyOP, we have established orthologs in Homo for 82%
      (15,250) of Monodelphis gene predictions. Those with single orthologs in each
      species exhibited a high median synonymous substitution rate (d(S) = 1.02),
      thereby explaining the relative paucity of aligned regions outside of coding
      sequences. Orthology assignments were used to construct a synteny map that
      illustrates the considerable fragmentation of Monodelphis and Homo karyotypes
      since their therian last common ancestor. Fifteen percent of Monodelphis genes
      are predicted, from their low divergence at synonymous sites, to have been
      duplicated in the metatherian lineage. The majority of Monodelphis-specific genes
      possess predicted roles in chemosensation, reproduction, adaptation to specific
      diets, and immunity. Using alignments of Monodelphis genes to sequences from
      either Homo or Trichosurus vulpecula (an Australian marsupial), we show that
      metatherian X chromosomes have elevated silent substitution rates and high G+C
      contents in comparison with both metatherian autosomes and eutherian chromosomes.
      Each of these elevations is also a feature of subtelomeric chromosomal regions.
      We attribute these observations to high rates of female-specific recombination
      near the chromosomal ends and within the X chromosome, which act to sustain or
      increase G+C levels by biased gene conversion. In particular, we propose that the
      higher G+C content of the Monodelphis X chromosome is a direct consequence of its
      small size relative to the giant autosomes.

PMID- 17495011
TI  - Characterization of the opossum immune genome provides insights into the
      evolution of the mammalian immune system.
AB  - The availability of the first marsupial genome sequence has allowed us to
      characterize the immunome of the gray short-tailed opossum (Monodelphis
      domestica). Here we report the identification of key immune genes, including the
      highly divergent chemokines, defensins, cathelicidins, and Natural Killer cell
      receptors. It appears that the increase in complexity of the mammalian immune
      system occurred prior to the divergence of the marsupial and eutherian lineages
      approximately 180 million years ago. Genomes of ancestral mammals most likely
      contained all of the key mammalian immune gene families, with evolution on
      different continents, in the presence of different pathogens leading to lineage
      specific expansions and contractions, resulting in some minor differences in gene
      number and composition between different mammalian lineages. Gene expansion and
      extensive heterogeneity in opossum antimicrobial peptide genes may have evolved
      as a consequence of the newborn young needing to survive without an adaptive
      immune system in a pathogen laden environment. Given the similarities in the
      genomic architecture of the marsupial and eutherian immune systems, we propose
      that marsupials are ideal model organisms for the study of developmental
      immunology.

PMID- 17495013
TI  - Biomechanical analysis of an isolated fibular (lateral) collateral ligament
      reconstruction using an autogenous semitendinosus graft.
AB  - BACKGROUND: The fibular collateral ligament is the primary stabilizer to varus
      instability of the knee. Untreated fibular collateral ligament injuries can lead
      to residual knee instability and can increase the risk of concurrent cruciate
      ligament reconstruction graft failures. Anatomic reconstructions of the fibular
      collateral ligament have not been biomechanically validated. PURPOSE: To describe
      an anatomic fibular collateral ligament reconstruction using an autogenous
      semitendinosus graft and to test the hypothesis that using this reconstruction
      technique to treat an isolated fibular collateral ligament injury will restore
      the knee to near normal stability. STUDY DESIGN: Controlled laboratory study.
      METHODS: Ten nonpaired, fresh-frozen cadaveric knees were biomechanically
      subjected to a 10 N.m varus moment and 5 N.m external and internal rotation
      torques at 0 degrees, 15 degrees, 30 degrees, 60 degrees, and 90 degrees of knee
      flexion. Testing was performed with an intact and sectioned fibular collateral
      ligament, and also after an anatomic reconstruction of the fibular collateral
      ligament with an autogenous semitendinosus graft. Motion changes were assessed
      with a 6 degree of freedom electromagnetic motion analysis system. RESULTS: After
      sectioning, we found significant increases in varus rotation at 0 degrees, 15
      degrees, 30 degrees, 60 degrees, and 90 degrees, external rotation at 60 degrees
      and 90 degrees, and internal rotation at 0 degrees, 15 degrees, 30 degrees, 60
      degrees, and 90 degrees of knee flexion. After reconstruction, there were
      significant decreases in motion in varus rotation at 0 degrees, 15 degrees, 30
      degrees, 60 degrees, and 90 degrees, external rotation at 60 degrees and 90
      degrees, and internal rotation at 0 degrees, 15 degrees, and 30 degrees of knee
      flexion. In addition, we observed a full recovery of knee stability in varus
      rotation at 0 degrees, 60 degrees, and 90 degrees, external rotation at 60
      degrees and 90 degrees, and internal rotation at 0 degrees and 30 degrees of knee
      flexion. CONCLUSION: An anatomic fibular collateral ligament reconstruction
      restores varus, external, and internal rotation to near normal stability in a
      knee with an isolated fibular collateral ligament injury. CLINICAL SIGNIFICANCE:
      An anatomic reconstruction of the fibular collateral ligament with an autogenous
      semitendinosus graft is a viable option to treat nonrepairable acute or chronic
      fibular collateral ligament tears in patients with varus instability.

PMID- 17495012
TI  - Evolutionary dynamics of transposable elements in the short-tailed opossum
      Monodelphis domestica.
AB  - The genome of the gray short-tailed opossum Monodelphis domestica is notable for
      its large size ( approximately 3.6 Gb). We characterized nearly 500 families of
      interspersed repeats from the Monodelphis. They cover approximately 52% of the
      genome, higher than in any other amniotic lineage studied to date, and may
      account for the unusually large genome size. In comparison to other mammals,
      Monodelphis is significantly rich in non-LTR retrotransposons from the LINE-1,
      CR1, and RTE families, with >29% of the genome sequence comprised of copies of
      these elements. Monodelphis has at least four families of RTE, and we report
      support for horizontal transfer of this non-LTR retrotransposon. In addition to
      short interspersed elements (SINEs) mobilized by L1, we found several families of
      SINEs that appear to use RTE elements for mobilization. In contrast to L1
      mobilized SINEs, the RTE-mobilized SINEs in Monodelphis appear to shift from G+C
      rich to G+C-low regions with time. Endogenous retroviruses have colonized
      approximately 10% of the opossum genome. We found that their density is enhanced
      in centromeric and/or telomeric regions of most Monodelphis chromosomes. We
      identified 83 new families of ancient repeats that are highly conserved across
      amniotic lineages, including 14 LINE-derived repeats; and a novel SINE element,
      MER131, that may have been exapted as a highly conserved functional noncoding
      RNA, and whose emergence dates back to approximately 300 million years ago. Many
      of these conserved repeats are also present in human, and are highly over
      represented in predicted cis-regulatory modules. Seventy-six of the 83 families
      are present in chicken in addition to mammals.

PMID- 17495014
TI  - A model for an uncertainty budget for preanalytical variables in clinical
      chemistry analyses.
AB  - BACKGROUND: We sought a practical method to calculate preanalytical
      uncertainties. In clinical chemistry measurements, the combined preanalytical
      uncertainty is a function of the magnitude and probability distribution of the
      different uncertainty sources and the number of such sources. METHODS: Results
      from an optimal practice for handling of the blood samples (termed the standard
      method) were compared with alternative methods that deviate from the standard
      method but are used in current practice. For categorically distributed
      uncertainty sources (e.g., use of different kinds of blood tubes), alternative
      treatments were modeled discretely using a known probability distribution for
      each alternative. For continuously distributed sources (e.g., clotting time), we
      assumed a rectangular distribution. We calculated the expectation, variance, and
      SD of differences between results from current practice and the standard method.
      We tabulated uncertainty budgets for the differences between current practice and
      the standard method for each uncertainty source. The expected individual biases
      and variances were summed to obtain the combined expected bias and variance.
      RESULTS: The combined expected bias (SD) for glucose was -0.15 (0.130) mmol/L,
      with prolonged clotting time giving the greatest contribution. The combined
      expected bias (SD) for calcium was -0.011 (0.0182) mmol/L, for magnesium 0.006
      (0.026) mmol/L, and for creatinine 0.5 (1.81) micromol/L. CONCLUSION: By
      comparing a standard method for preanalytical sample handling to alternative
      methods used in current practice, and considering the distribution of alternative
      methods, our modeling approach allows the development of an uncertainty budget
      for preanalytical variables in clinical chemistry analyses.

PMID- 17495015
TI  - 6-thioguanine nucleotide-adapted azathioprine therapy does not lead to higher
      remission rates than standard therapy in chronic active crohn disease: results
      from a randomized, controlled, open trial.
AB  - BACKGROUND: A prospective randomized trial in patients with Crohn disease studied
      whether 6-thioguanine nucleotide (6-TGN) concentration-adapted azathioprine (AZA)
      therapy is clinically superior to a standard dose of 2.5 mg/kg/day AZA. METHODS:
      After 2 weeks of standard therapy, patients (n = 71) were randomized into
      standard (n = 32) or adapted-dose (n = 25) groups; 14 patients dropped out before
      randomization. In the adapted group, the AZA dose was adjusted to maintain 6-TGN
      concentrations between 250 and 400 pmol/8 x 10(8) erythrocytes (Ery). Response
      criteria were the number of patients in remission after 16 weeks without steroids
      (primary) and remission after 24 weeks, frequency of side effects, and quality of
      life (secondary). RESULTS: After 16 weeks, 14 of 32 (43.8%) patients in the
      standard group vs 11 of 25 (44%) in the adapted group were in remission without
      steroids (intent-to-treat analysis). After 24 weeks, 43.8% vs 40% were in
      remission. No significant differences were found concerning quality of life,
      disease activity, 6-TGN concentrations, AZA dose, or dropouts due to side
      effects. Sixty-six patients had a wild-type thiopurine S-methyltransferase (TPMT)
      genotype, with TPMT activities of 8 to 20 nmol/(mL Ery x h). Five patients
      (dropouts after randomization) were heterozygous, with TPMT activities <8
      nmol/(mL Ery x h). 6-Methyl mercaptopurine (6-MMP) concentrations >5700 pmol/8 x
      10(8) Ery were not associated with hepatotoxicity. CONCLUSION: Standard and
      adapted dosing with the provided dosing scheme led to identical 6-TGN
      concentrations and remission rates. Adapted dosing had no apparent clinical
      benefit for patients with TPMT activity between 8 and 20 nmol/(mL Ery x h).
      Additionally, 6-MMP monitoring had no predictive value for hepatotoxicity.

PMID- 17495016
TI  - Increased plasma concentrations of soluble CD40 ligand in acute coronary syndrome
      depend on in vitro platelet activation.
AB  - BACKGROUND: Soluble CD40 ligand (sCD40L) was suggested as a novel biomarker of
      cardiovascular risk. We examined the effect of preanalytical variation on the
      measurement of sCD40L concentration. METHODS: From healthy control individuals (n
      = 20) and patients with acute coronary syndrome (ACS) (n = 20) or sepsis (n =
      20), we obtained blood drawn into 5 tubes containing citrate or a mixture of
      citrate, theophylline, adenosine, and dipyridamole (CTAD). The tubes were
      incubated for 30 min at room temperature or 0 degrees C before a single or double
      centrifugation (15 min, 2500 g) at room temperature or 4 degrees C, respectively.
      sCD40L, beta-thromboglobulin (betaTG), and platelet factor 4 (PF4) concentrations
      were measured using immunoassays. RESULTS: Concentrations of sCD40L were very low
      in all CTAD and citrated samples maintained at 0 degrees C (median < or = 0.076
      microg/L). Although increased betaTG and PF4 confirmed disease-related in vivo
      platelet activation, sCD40L was not higher in patients than in controls. In
      contrast, if the samples were processed at room temperature, sCD40L was
      significantly higher in ACS patients than in controls (P <0.02 in CTAD and
      citrated plasma at room temperature). Moreover, the betaTG:PF4 ratio decreased in
      patient but not control CTAD samples, suggesting a greater susceptibility of
      patient platelets to in vitro activation. CONCLUSIONS: Increased sCD40L
      concentrations resulted from in vitro platelet activation during sample
      preparation. Disease-related in vivo activation did not contribute to sCD40L
      concentrations in plasma. Therefore, published studies of sCD40L demand cautious
      interpretation, because their preanalytical conditions were not standardized.

PMID- 17495017
TI  - Intraindividual stability of human erythrocyte cholinesterase activity.
AB  - BACKGROUND: Erythrocyte cholinesterase (RBC-ChE) activities serve as useful and
      sensitive biomarkers to monitor exposure to cholinesterase-inhibiting substances,
      such as chemical warfare nerve agents and pesticides. Although the
      interindividual variation of RBC-ChE is well characterized, the magnitude of
      intraindividual variation for RBC-ChE remains controversial. An accurate measure
      of intraindividual variation is critical for establishing the appropriate
      frequency of RBC-ChE testing. METHODS: We retrospectively tracked the
      intraindividual variation of RBC-ChE activities among 46 male nerve agent workers
      from a single US Army depot that participated in a medical surveillance program
      requiring periodic RBC-ChE monitoring. All RBC-ChE analysis was performed by the
      same medical laboratory technician by the delta pH method. RESULTS: A mean of 38
      and a median of 37 RBC-ChE measurements were available for each worker. The mean
      duration of employment for these workers was 20 years (median, 21 years). The
      mean CV for RBC-ChE in this set of 46 workers was 3.9%. Linear regression
      analysis of the data for each worker resulted in a mean slope of 0.0010 delta pH
      units/h per year. CONCLUSIONS: RBC-ChE activities increased in each person by a
      mean of 0.01 delta pH units/h every 10 years, which is a negligible rate. These
      findings highlight the stability of RBC-ChE activities over time in a given
      individual and may have important policy implications regarding the appropriate
      frequency of RBC-ChE testing.

PMID- 17495018
TI  - Quantification of alkylresorcinol metabolites in urine by HPLC with coulometric
      electrode array detection.
AB  - BACKGROUND: Whole-grain rye and wheat cereals contain high amounts of
      alkylresorcinols (ARs), phenolic lipids. ARs can be quantified in plasma. Two
      recently identified urinary AR metabolites, 3,5-dihydroxyphenylbenzoic acid
      (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), may be useful as
      biomarkers of intake of whole-grain rye and wheat. METHODS: We evaluated 4
      pretreatment protocols for quantifying urinary DHBA and DHPPA using HPLC coupled
      with a coulometric electrode array detector. Syringic acid was used as the
      internal calibrator. RESULTS: Measured urinary concentrations of DHBA and DHPPA
      were 0.8-115 micromol/L. The mean recoveries of all added concentrations were 85%
      104% for DHBA and 86%-99% for DHPPA, depending on the degree of the purification.
      The protocol versions with less purification correlated well with the protocol
      including highest purification. The correlation coefficients (r(2)) were 0.9699
      0.8153 for DHBA and 0.9854-0.8371 for DHPPA. CONCLUSION: Although the protocol
      with the most purification steps was most specific, all protocols were suitable
      for measuring DHBA and DHPPA in urine. The rapid protocol with simple hydrolysis
      could be used in large-scale clinical studies. Additional investigation is needed
      to clarify whether these metabolites are useful biomarkers of whole-grain intake
      and helpful in the exploration of its association with human diseases.

PMID- 17495019
TI  - Selected exonic sequencing of the AGXT gene provides a genetic diagnosis in 50%
      of patients with primary hyperoxaluria type 1.
AB  - BACKGROUND: Definitive diagnosis of primary hyperoxaluria type 1 (PH1) requires
      analysis of alanine:glyoxylate aminotransferase (AGT) activity in the liver. We
      have previously shown that targeted screening for the 3 most common mutations in
      the AGXT gene (c.33_34insC, c.508G>A, and c.731T>C) can provide a molecular
      diagnosis in 34.5% of PH1 patients, eliminating the need for a liver biopsy.
      Having reviewed the distribution of all AGXT mutations, we have evaluated a
      diagnostic strategy that uses selected exon sequencing for the molecular
      diagnosis of PH1. METHODS: We sequenced exons 1, 4, and 7 for 300 biopsy
      confirmed PH1 patients and expressed the identified missense mutations in vitro.
      RESULTS: Our identification of at least 1 mutation in 224 patients (75%) and 2
      mutations in 149 patients increased the diagnostic sensitivity to 50%. We
      detected 29 kinds of sequence changes, 15 of which were novel. Four of these
      mutations were in exon 1 (c.2_3delinsAT, c.30_32delCC, c.122G>A, c.126delG), 7
      were in exon 4 (c.447_454delGCTGCTGT, c.449T>C, c.473C>T, c.481G>A, c.481G>T,
      c.497T>C, c.424-2A>G), and 4 were in exon 7 (c.725insT, c.737G>A, c.757T>C, c.776
      + 1G>A). The missense changes were associated with severely decreased AGT
      catalytic activity and negative immunoreactivity when expressed in vitro.
      Missense mutation c.26C>A, previously described as a pathological mutation, had
      activity similar to that of the wild-type enzyme. CONCLUSIONS: Selective exon
      sequencing can allow a definitive diagnosis in 50% of PH1 patients. The test
      offers a rapid turnaround time (15 days) with minimal risk to the patient.
      Demonstration of the expression of missense changes is essential to demonstrate
      pathogenicity.

PMID- 17495020
TI  - Digoxin-like immunoreactive factors induce apoptosis in human acute T-cell
      lymphoblastic leukemia.
AB  - BACKGROUND: Plant-derived cardenolides reportedly possess anticancer properties
      in human leukemic cells via selective induction of apoptosis, cell cycle arrest,
      and differentiation. Selective induction of apoptosis with mammalian-derived
      digoxin-like immunoreactive factor (DLIF) could provide new strategies for
      anticancer drug development or the identification of biomarkers for cancer. We
      investigated whether DLIFs selectively induce apoptosis in human lymphoblastic
      leukemic cells. METHODS: We compared the relative potencies of digoxin, ouabain,
      and DLIF on induction of programmed cell death in Jurkat cells (an acute T
      leukemic cell line), K-562 (a myelogenous leukemia cell line), and nonpathologic
      human peripheral blood mononuclear cells (PBMCs). Apoptosis was measured by flow
      cytometry with the annexin V/propidium iodide method. RESULTS: Digoxin and
      ouabain induced apoptosis in Jurkat cells [digoxin 50% inhibitory concentration
      (IC(50)), 24 nmol/L; ouabain IC(50), 26 nmol/L]. Neither digoxin nor ouabain
      induced apoptosis in K-562 cells or PBMCs. DLIF was more potent (IC(50), 1.9
      nmol/L) and >2-fold more effective than digoxin or ouabain at inducing maximum
      apoptosis in Jurkat cells. The IC(50) values in the apoptosis assays were >100
      fold lower (DLIF) and 20-fold lower (digoxin and ouabain) than the IC(50)
      required for Na(+)- and K(+)-dependent ATPase (DLIF, 200 nmol/L; digoxin, 910
      nmol/L; ouabain, 600 nmol/L). CONCLUSION: DLIF selectively induces apoptosis in a
      human acute T-cell lymphoblastic leukemia cell line but not in K-562 cells or
      PBMCs. These data suggest a new physiological role for these endogenous hormone
      like factors.

PMID- 17495021
TI  - Comparison of brain natriuretic peptide (BNP) and amino-terminal ProBNP for early
      diagnosis of heart failure.
AB  - BACKGROUND: We compared the diagnostic accuracy of brain natriuretic peptide
      (BNP) and amino-terminal proBNP (NT-proBNP) for diagnosis of preclinical and mild
      heart failure (HF). METHODS: We assayed plasma NT-proBNP and BNP in 182 healthy
      controls and in a prospective cohort of 820 HF patients divided according to the
      American Heart Association/American College of Cardiology classification. These
      included 86 patients in stage A [mean (SE) ejection fraction 61% (1%); mean (SE)
      age 47 (2) years], 255 in stage B [65% (2%); 62 (1) years], 420 patients in stage
      C [35% (1%); 68 (1) years] and 59 in stage D [25% (1%); 74 (1) years]. Diagnostic
      accuracies of BNP and NT-proBNP were evaluated by ROC analysis, and a
      multivariate linear regression model was applied to predict HF staging. RESULTS:
      Median BNP and NT-proBNP concentrations increased from stage A to D 57-fold and
      107-fold, respectively. Both assays were accurate (P <0.001) in separating stage
      B from controls or stage A, and stage C from controls or stage A or B. NT-proBNP
      was more accurate (P <0.001) than BNP in differentiating stage C from stages A
      and B patients and controls and was a better predictor of HF classification in a
      model including age, sex, and renal function (P <0.001). CONCLUSIONS: Monitoring
      BNP or NT-proBNP enabled identification of asymptomatic patients at risk for the
      development of HF. NT-proBNP showed better accuracy than BNP for identifying mild
      HF.

PMID- 17495022
TI  - Mass spectral determination of fasting tear glucose concentrations in nondiabetic
      volunteers.
AB  - BACKGROUND: There is considerable disagreement regarding the concentration of
      glucose in tears and its relationship to the concentration in blood. Improved
      sampling and analysis methods may resolve these discrepancies and possibly
      provide a basis for in situ tear glucose sensors. METHODS: We used liquid
      chromatography (LC) with electrospray ionization mass spectrometry (ESI-MS) to
      determine glucose in 1-muL tear fluid samples obtained from 25 fasting study
      participants. Tear fluid was collected with microcapillaries and a slitlamp
      microscope. RESULTS: The median (range) of fasting tear glucose concentrations
      was 28 (7-161) micromol/L or 0.50 (0.13-2.90) mg/dL. The SD of tear glucose
      measurements for individuals varied linearly with the mean tear glucose
      concentration and was approximately half of the mean. We found no significant
      difference in tear glucose concentrations between contact lens users and nonusers
      (P = 0.715). We observed significant correlations between fasting blood and tear
      glucose concentrations (R = 0.50, P = 0.01). CONCLUSIONS: Our tear fluid
      collection and analysis method enables reliable measurement of equilibrium,
      fasting tear glucose concentrations. These concentrations are lower than those
      previously reported for nondiabetic persons. Larger population studies are
      required to determine correlations between blood and tear glucose concentrations
      and to determine the utility of contact lens-based sensors for the monitoring of
      diabetes. Our methods are applicable for study of other tear fluid analytes and
      may prove useful for monitoring other disease states.

PMID- 17495026
TI  - The tumor suppressor CYLD regulates entry into mitosis.
AB  - Mutations in the cylindromatosis (CYLD) gene cause benign tumors of skin
      appendages, referred to as cylindromas. The CYLD gene encodes a deubiquitinating
      enzyme that removes Lys-63-linked ubiquitin chains from I kappa B kinase
      signaling components and thereby inhibits NF-kappaB pathway activation. The
      dysregulation of NF-kappaB activity has been proposed to promote cell
      transformation in part by increasing apoptosis resistance, but it is not clear
      whether this is CYLD's only or predominant tumor-suppressing function. Here, we
      show that CYLD is also required for timely entry into mitosis. Consistent with a
      cell-cycle regulatory function, CYLD localizes to microtubules in interphase and
      the midbody during telophase, and its protein levels decrease as cells exit from
      mitosis. We identified the protein kinase Plk1 as a potential target of CYLD in
      the regulation of mitotic entry, based on their physical interaction and similar
      loss-of-function and overexpression phenotypes. Our findings raise the
      possibility that, as with other genes regulating tumorigenesis, CYLD has not only
      tumor-suppressing (apoptosis regulation) but also tumor-promoting activities
      (enhancer of mitotic entry). We propose that this additional function of CYLD
      could provide an explanation for the benign nature of most cylindroma lesions.

PMID- 17495027
TI  - Angiotensin II up-regulates soluble epoxide hydrolase in vascular endothelium in
      vitro and in vivo.
AB  - Epoxyeicosatrienoic acids (EETs), as metabolites of arachidonic acid, may
      function as antihypertensive and antiatherosclerotic mediators for vasculature.
      EETs are degraded by soluble epoxide hydrolase (sEH). Pharmacological inhibition
      and genetic ablation of sEH have been shown to increase the level of EETs, and
      treating angiotensin II (Ang II)-infused hypertension rats with sEH-selective
      inhibitors increased the levels of EETs, with attendant decrease in systolic
      blood pressure. To elucidate the mechanisms by which Ang II regulates sEH
      expression, we treated human umbilical vein endothelial cells (ECs) and bovine
      aortic ECs with Ang II and found increased sEH expression at both the mRNA and
      protein levels. Transient transfection assays showed that the activity of the
      human sEH promoter was increased in ECs in response to Ang II. Further analysis
      of the promoter region of the sEH gene demonstrated that treatment with Ang II,
      like overexpression of c-Jun/c-Fos, activates the sEH promoter through an AP-1
      binding motif. The binding of c-Jun to the AP-1 site of the sEH promoter was
      confirmed by chromatin immunoprecipitation assays. In contrast, adenovirus
      overexpression of the dominant-negative mutant of c-Jun significantly attenuated
      the effects of Ang II on sEH induction. An elevated level of sEH was found in the
      aortic intima of both spontaneously hypertensive rats and Ang II-infused Wistar
      rats. Blocking Ang II binding to Ang II receptor 1 by losartan abolished the sEH
      induction. Thus, AP-1 activation is involved in the transcriptional up-regulation
      of sEH by Ang II in ECs, which may contribute to Ang II-induced hypertension.

PMID- 17495029
TI  - Mutations in clusters and showers.

PMID- 17495028
TI  - MPS3 mediates meiotic bouquet formation in Saccharomyces cerevisiae.
AB  - In meiotic prophase, telomeres associate with the nuclear envelope and accumulate
      adjacent to the centrosome/spindle pole to form the chromosome bouquet, a well
      conserved event that in Saccharomyces cerevisiae requires the meiotic telomere
      protein Ndj1p. Ndj1p interacts with Mps3p, a nuclear envelope SUN domain protein
      that is required for spindle pole body duplication and for sister chromatid
      cohesion. Removal of the Ndj1p-interaction domain from MPS3 creates an ndj1 Delta
      like separation-of-function allele, and Ndj1p and Mps3p are codependent for
      stable association with the telomeres. SUN domain proteins are found in the
      nuclear envelope across phyla and are implicated in mediating interactions
      between the interior of the nucleus and the cytoskeleton. Our observations
      indicate a general mechanism for meiotic telomere movements.

PMID- 17495030
TI  - Phosphatidylinositol 3-kinase is involved in prostaglandin E2-mediated murine
      duodenal bicarbonate secretion.
AB  - Prostaglandin E(2) (PGE(2)) plays an important role in the regulation of duodenal
      bicarbonate (HCO(3)(-)) secretion, but its signaling pathway(s) are not fully
      understood. In the present study, we investigated the signaling pathways involved
      in PGE(2)-mediated duodenal HCO(3)(-) secretion. Murine duodenal mucosal HCO(3)(
      ) secretion was examined in vitro in Ussing chambers by pH-stat titration in the
      presence of a variety of signal transduction modulators. Phosphatidylinositol 3
      kinase (PI3K) activity was measured by immunoprecipitation of PI3K and ELISA, and
      Akt phosphorylation was measured by Western analysis with anti-phospho-Akt and
      anti-Akt antibodies. PGE(2)-stimulated duodenal HCO(3)(-) secretion was reduced
      by the cAMP-dependent signaling pathway inhibitors MDL-12330A and KT-5720 by 23%
      and 20%, respectively; the Ca(2+)-influx inhibitor verapamil by 26%; and the
      calmodulin antagonist W-13 by 24%; whereas the PI3K inhibitors wortmannin and LY
      294002 reduced PGE(2)-stimulated HCO(3)(-) secretion by 51% and 47%,
      respectively. Neither the MAPK inhibitor PD-98059 nor the tyrosine kinase
      inhibitor genistein altered PGE(2)-stimulated HCO(3)(-) secretion. PGE(2)
      application caused a rapid and concentration-dependent increase in duodenal
      mucosal PI3K activity and Akt phosphorylation. These results demonstrated that
      PGE(2) activates PI3K in duodenal mucosa and stimulates duodenal HCO(3)(-)
      secretion via cAMP-, Ca(2+)-, and PI3K-dependent signaling pathways.

PMID- 17495031
TI  - Development and physiological regulation of intestinal lipid absorption. I.
      Development of intestinal lipid absorption: cellular events in chylomicron
      assembly and secretion.
AB  - The newborn mammal must efficiently absorb dietary fat, predominantly as
      triacylglycerol, and produce chylomicrons to deliver this lipid to peripheral
      tissues. The cellular mechanisms involved in enterocyte chylomicron assembly have
      recently been elucidated, and data on their regulation in the immature gut are
      beginning to emerge. This review focuses on key proteins involved in chylomicron
      assembly: apolipoprotein B-48, microsomal triglyceride transfer protein, and
      apolipoprotein A-IV. Recent studies support a role for apolipoprotein A-IV in
      enhancing chylomicron secretion by promoting production of larger particles.
      These proteins are regulated in a manner to maximize the lipid absorptive
      capacity of the newborn intestine.

PMID- 17495032
TI  - Leptin modulates the expression of secreted and membrane-associated mucins in
      colonic epithelial cells by targeting PKC, PI3K, and MAPK pathways.
AB  - Mucins play an essential role in the protection and repair of gastrointestinal
      mucosa. We recently showed that luminal leptin strongly stimulated mucin
      secretion in vivo in rat colon. In the present study, we challenged the
      hypothesis that leptin may act directly on goblet cells to induce mucin
      expression in rat and human intestinal mucin-producing cells (DHE and HT29-MTX).
      The endoluminal effect of leptin was also studied in vivo in rat perfused colon
      model. The presence of leptin receptors was demonstrated in the two cell lines by
      Western blot and RT-PCR. In rat DHE cells, leptin (0.01-10 nmol/l, 60 min) dose
      dependently increased the secretion of mucins (210 +/- 3% of controls) and the
      expression of Muc2, Muc3, and Muc4 (twofold basal level) but not of Muc1 and
      Muc5AC. Luminal perfusion of leptin (60 min, 0.1-100 nmol/l) in rat colon also
      increased the mRNA level of Muc2, Muc3, and Muc4 but not of Muc1. In human HT29
      MTX cells, leptin (0.01-10 nmol/l, 60 min) dose dependently enhanced MUC2,
      MUC5AC, and MUC4 mRNA levels. These effects were prevented by pretreatment of
      cells with the leptin mutein L39A/D40A/F41A, which acts as a receptor antagonist.
      Finally, pathway inhibition experiments suggest that leptin increased mucin
      expression by activating PKC-, phosphatidyl inositol 3-kinase-, and MAPK
      dependent pathways but not the JAK/STAT pathway. In conclusion, leptin may
      contribute significantly to membrane-associated and secreted mucin production via
      a direct stimulation of colonic epithelial cells and the activation of leptin
      receptors. These data are consistent with a role for leptin in regulation of the
      intestinal barrier function.

PMID- 17495033
TI  - Glutamatergic synaptic inputs and ICAN: the basis for an emergent property
      underlying respiratory rhythm generation?

PMID- 17495034
TI  - Neurally released pituitary adenylate cyclase-activating polypeptide enhances
      guinea pig intrinsic cardiac neurone excitability.
AB  - Intracellular recordings were made in vitro from guinea-pig cardiac ganglia to
      determine whether endogenous neuropeptides such as pituitary adenylate cyclase
      activating polypeptide (PACAP) or substance P released during tetanic neural
      stimulation modulate cardiac neurone excitability and/or contribute to slow
      excitatory postsynaptic potentials (sEPSPs). When nicotinic and muscarinic
      receptors were blocked by hexamethonium and atropine, 20 Hz stimulation for 10 s
      initiated a sEPSP in all innervated neurones. In 40% of the cells, excitability
      was enhanced after termination of the sEPSP. This suggested that non-cholinergic
      receptor-mediated mechanisms contributed to the sEPSP and modulated neuronal
      excitability. Exogenous PACAP and substance P initiated a slow depolarization in
      the neurones whereas neuronal excitability was only increased by PACAP. When
      ganglia were treated with the PAC1 antagonist PACAP6-38 (500 nM), the sEPSP
      evoked by 20 Hz stimulation was reduced by approximately 50% and an enhanced
      excitability occurred in only 10% of the cells. These observations suggested that
      PACAP released from preganglionic nerve terminals during tetanic stimulation
      enhanced neuronal excitability and evoked sEPSPs. After addition of 1 nM PACAP to
      the bath, 7 of 9 neurones exhibited a tonic firing pattern whereas in untreated
      preparations, the neurons had a phasic firing pattern. PACAP6-38 (500 nM)
      diminished the increase in excitability caused by 1 nM PACAP so that only 4 of 13
      neurones exhibited a tonic firing pattern and the other 9 cells retained a phasic
      firing pattern. These findings indicate that PACAP can be released by tetanic
      neural stimulation in vitro and increase the excitability of intrinsic cardiac
      neurones. We hypothesize that in vivo PACAP released during preganglionic firing
      may modulate neurotransmission within the intrinsic cardiac ganglia.

PMID- 17495035
TI  - Genetically manipulated mice: a powerful tool with unsuspected caveats.
AB  - Although genetic manipulations in mice have provided a powerful tool for
      investigating gene function in vivo, recent studies have uncovered a number of
      developmental phenomena that complicate the attribution of phenotype to the
      specific genetic change. A more realistic approach has been to modulate gene
      expression and function in a temporal and tissue-specific manner. The most common
      of these methods, the CreLoxP and tetracycline response systems, are surveyed
      here and their recently identified shortcomings discussed, along with a less well
      known system based on the E. coli lac operon and modified for use in mammals. The
      potential for further complications in interpretation due to hitherto unexpected
      epigenetic effects involving transfer of RNA or protein in oocytes or sperm is
      also explored. Given these problems we reiterate the necessity for the use of
      completely reversible methods that will allow each experimental group of animals
      to act as their own control. Using these methods with a number of specific
      modifications to eliminate non-specific effects from random insertion sites and
      inducer molecules, the full potential of genetic manipulation studies should be
      realized.

PMID- 17495036
TI  - Astrocytic glutamate targets NMDA receptors.

PMID- 17495037
TI  - Dopamine and working memory mechanisms in prefrontal cortex.

PMID- 17495038
TI  - Characterization of flow and mixing regimes within the ileum of the brushtail
      possum using residence time distribution analysis with simultaneous spatio
      temporal mapping.
AB  - We studied the flow and mixing regimes in isolated segments of the terminal ileum
      of brushtail possums during spontaneous circumferential and longitudinal
      contractions under conditions that allowed backflow and compared them with those
      of inactive segments. Residence time distributions (RTDs) were determined by
      perfusion with two probes of different rheological properties to which an inert
      dye marker was added. Ileal segment volume and oscillatory flow during the period
      of RTD determination were derived from spatiotemporal maps. High viscosity guar
      gum solution generated RTDs characteristic of laminar flow in inactive ileal
      segments which confirmed that no slip was occurring at the mucosal layer. In
      active segments, motility and consequent oscillatory flow imparted significant
      additional axial dispersion to the flow patterns of both probes. Mixing occurred
      episodically during periods when intestinal volume was reduced and onflow was
      augmented by peristalsis, which may prevent the establishment of steady state
      conditions. Marker concentration rose more steeply when active ileal segments
      were being perfused with a probe of similar viscosity to normal digesta than with
      low viscosity Earle's/Hepes solution, each being subject to similar levels of
      oscillatory flow. This indicated that a coarser mixing regime prevailed and that
      absorption of nutrients from viscous digesta would rely to a greater degree on
      molecular diffusion.

PMID- 17495039
TI  - Deciphering the nitric oxide to carbon monoxide lung transfer ratio:
      physiological implications.
AB  - Using simultaneous nitric oxide and carbon monoxide lung transfer measurements
      (T(LNO) and T(LCO)), the membrane transfer capacity (D(m)) and capillary lung
      volume (V(c)) as well as the dimensionless ratio T(LNO)/T(LCO) can be calculated.
      The significance of this ratio is yet unclear. Theoretically, the T(LNO)/T(LCO)
      ratio should be inversely related to the product of both lung alveolar capillary
      membrane (mu) and blood sheet thicknesses (K). NO and CO transfers were measured
      in healthy subjects in various conditions likely to be associated with changes in
      K and/or mu. Experimentally, deflation of the lung from 7.4 to 4.8 l decreased
      the T(LNO)/T(LCO) ratio from 4.9 to 4.2 (n=25) which was consistent mainly with a
      thickening of the blood sheet. Compared with continuous negative pressure
      breathing, continuous positive pressure breathing increased this ratio suggesting
      a thinning of the capillary sheet. It was also observed with 12 healthy subjects
      that slight haemodilution that may thicken the blood sheet decreased the
      T(LNO)/T(LCO) ratio from 4.85 to 4.52. In conclusion, the T(LNO)/T(LCO) ratio is
      related to the thickness of the alveolar blood barrier. This ratio provides novel
      information for the analysis of the diffusion properties.

PMID- 17495040
TI  - Dual GABAA receptor-mediated inhibition in rat presympathetic paraventricular
      nucleus neurons.
AB  - The inhibitory neurotransmitter GABA plays a key role in the modulation of
      paraventricular nucleus (PVN) neuronal excitability and sympathoexcitatory
      outflow, under both physiological and pathological conditions. In addition to
      mediating conventional synaptic transmission (phasic inhibition), GABA(A)
      receptors of distinct biophysical, molecular and pharmacological properties have
      been recently found to underlie a slower, persistent form of inhibition (tonic
      inhibition). Whether the 'tonic' inhibitory modality is present in presympathetic
      PVN neurons, and what its role is in modulating their activity is at present
      unknown. Here, we combined tract-tracing techniques with patch-clamp
      electrophysiology to address these questions. Recordings obtained from PVN-RVLM
      (rostral ventrolateral medulla) projecting neurons show that besides blocking
      GABA(A)-mediated inhibitory postsynaptic currents (IPSCs, I(phasic)), the GABA(A)
      receptor blockers bicuculline and picrotoxin caused an outward shift in the
      holding current (I(tonic)). Conversely, the high affinity GABA(A) blocker
      gabazine blocked I(phasic) without affecting I(tonic). THIP, a GABA(A) receptor
      agonist that preferentially activates delta- over gamma-containing receptors,
      enhanced the magnitude of I(tonic). Our results also indicate that during
      conditions of strong and/or synchronous synaptic activity, I(tonic) may be
      activated by spillover of synaptically released GABA. Blockade of I(tonic)
      induced membrane depolarization, increased firing activity, and enhanced the
      input-output function of PVN-RVLM neurons. Altogether, our results support the
      presence of a persistent GABA(A)-mediated inhibitory modality in presympathetic
      PVN neurons, which plays a major role in modulating their excitability and firing
      activity.

PMID- 17495041
TI  - Diverse Kir modulators act in close proximity to residues implicated in
      phosphoinositide binding.
AB  - Inwardly rectifying potassium (Kir) channels were the first shown to be directly
      activated by phosphoinositides in general and phosphatidylinositol bisphosphate
      (PIP(2)) in particular. Atomic resolution structures have been determined for
      several mammalian and bacterial Kir channels. Basic residues, identified through
      mutagenesis studies to contribute to the sensitivity of the channel to PIP(2),
      have been mapped onto the three dimensional channel structure and their
      localization has given rise to a plausible model that can explain channel
      activation by PIP(2). Moreover, mapping onto the three-dimensional channel
      structure sites involved in the modulation of Kir channel activity by a diverse
      group of regulatory molecules, revealed a striking proximity to residues
      implicated in phosphoinositide binding. These observations support the hypothesis
      that the observed dependence of diverse modulators on channel-PIP(2) interactions
      stems from their localization within distances that can affect PIP(2)-interacting
      residues.

PMID- 17495042
TI  - Glucose kinetics and exercise tolerance in mice lacking the GLUT4 glucose
      transporter.
AB  - The absence of GLUT4 severely impairs basal glucose uptake in vivo, but does not
      alter glucose homeostasis or circulating insulin. Glucose uptake in isolated
      contracting skeletal muscle (MGU) is also impaired by the absence of GLUT4, and
      onset of muscle fatigue is hastened. Whether the body can compensate and preserve
      glucose homeostasis during exercise, as it does in the basal state, is unknown.
      One aim was to test the effectiveness of glucoregulatory compensation for the
      absence of GLUT4 in vivo. The absence of GLUT4 was also used to further define
      the role of hexokinase (HK) II, which catalyses glucose phosphorylation after it
      is transported in the cell. HK II increases MGU during exercise, as well as
      exercise endurance. In the absence of GLUT4, HK II expression will not affect
      MGU. A second aim was to test whether, in the absence of GLUT4, HK II retains its
      ability to increase exercise endurance. Wild-type (WT), GLUT4 null (GLUT4(-/-)),
      and GLUT4 null overexpressing HK II (GLUT4(-/-)HK(Tg)) mice were studied using a
      catheterized mouse model that allows blood sampling and isotope infusions during
      treadmill exercise. The impaired capacity of working muscle to take up glucose in
      GLUT4(-/-) is partially offset by an exaggerated increase in the glucagon:
      insulin ratio, increased liver glucose production, hyperglycaemia, and a greater
      capillary density in order to increase the delivery of glucose to the exercising
      muscle of GLUT4(-/-). Hearts of GLUT4(-/-) also exhibited a compensatory increase
      in HK II expression and a paradoxical increase in glucose uptake. Exercise
      tolerance was reduced in GLUT4(-/-) compared to WT. As expected, MGU in GLUT4(-/
      )HK(Tg) was the same as in GLUT4(-/-). However, HK II overexpression retained its
      ability to increase exercise endurance. In conclusion, unlike the basal state
      where glucose homeostasis is preserved, hyperglycaemia results during exercise in
      GLUT4(-/-) due to a robust stimulation of liver glucose release in the face of
      severe impairments in MGU. Finally, studies in GLUT4(-/-)HK(Tg) show that HK II
      improves exercise tolerance, independent of its effects on MGU.

PMID- 17495043
TI  - Changes in firing pattern of lateral geniculate neurons caused by membrane
      potential dependent modulation of retinal input through NMDA receptors.
AB  - An optimal visual stimulus flashed on the receptive field of a retinal ganglion
      cell typically evokes a strong transient response followed by weaker sustained
      firing. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus,
      which receive their sensory input from retina, respond similarly except that the
      gain, in particular of the sustained component, changes with level of arousal.
      Several lines of evidence suggest that retinal input to TC neurons through NMDA
      receptors plays a key role in generation of the sustained response, but the
      mechanisms for the state-dependent variation in this component are unclear. We
      used a slice preparation to study responses of TC neurons evoked by trains of
      electrical pulses to the retinal afferents at frequencies in the range of visual
      responses in vivo. Despite synaptic depression, the pharmacologically isolated
      NMDA component gave a pronounced build-up of depolarization through temporal
      summation of the NMDA receptor mediated EPSPs. This depolarization could provide
      sustained firing, the frequency of which depended on the holding potential. We
      suggest that the variation of sustained response in vivo is caused mainly by the
      state-dependent modulation of the membrane potential of TC neurons which shifts
      the NMDA receptor mediated depolarization closer to or further away from the
      firing threshold. The pharmacologically isolated AMPA receptor EPSPs were rather
      ineffective in spike generation. However, together with the depolarization evoked
      by the NMDA component, the AMPA component contributed significantly to spike
      generation, and was necessary for the precise timing of the generated spikes.

PMID- 17495044
TI  - Mechanical influences on skeletal muscle vascular tone in humans: insight into
      contraction-induced rapid vasodilatation.
AB  - We tested the hypothesis that mechanical deformation of forearm blood vessels via
      acute increases in extravascular pressure elicits rapid vasodilatation in humans.
      In healthy adults, we measured forearm blood flow (Doppler ultrasound) and
      calculated forearm vascular conductance (FVC) responses to whole forearm
      compressions and isometric muscle contractions with the arm above heart level. We
      used several experimental protocols to gain insight into how mechanical factors
      contribute to contraction-induced rapid vasodilatation. The findings from the
      present study clearly indicate that acute increases in extravascular pressure
      (200 mmHg for 2 s) elicit a significant rapid vasodilatation in the human forearm
      (peak DeltaFVC approximately 155%). Brief, 6 s sustained compressions evoked the
      greatest vasodilatation (DeltaFVC approximately 260%), whereas the responses to
      single (2 s) and repeated compressions (five repeated 2 s compressions) were not
      significantly different (DeltaFVC approximately 155% versus approximately 115%,
      respectively). This mechanically induced vasodilatation peaks within 1-2 cardiac
      cycles, and thus is dissociated from the temporal pattern normally observed in
      response to brief muscle contractions ( approximately 4-7 cardiac cycles). A non
      linear relation was found between graded increases in extravascular pressure and
      both the immediate and peak rapid vasodilatory response, such that the responses
      increased sharply from 25 to 100 mmHg, with no significant further dilatation
      until 300 mmHg (maximal DeltaFVC approximately 185%). This was in contrast to the
      linear intensity-dependent relation observed with muscle contractions. Our
      collective findings indicate that mechanical influences contribute largely to the
      immediate vasodilatation (first cardiac cycle) observed in response to a brief,
      single contraction. However, it is clear that there are additional mechanisms
      related to muscle activation that continue to cause and sustain vasodilatation
      for several more cardiac cycles after contraction. Additionally, the potential
      contribution of mechanical influences to the total contraction-induced hyperaemia
      appears greatest for low to moderate intensity single muscle contractions, and
      this contribution becomes less significant for sustained and repeated
      contractions. Nevertheless, this mechanically induced vasodilatation could serve
      as a feedforward mechanism to increase muscle blood flow at the onset of
      exercise, as well as in response to changes in contraction intensity, prior to
      alterations in local vasodilating substances that influence vascular tone.

PMID- 17495045
TI  - Sweet taste receptors in rat small intestine stimulate glucose absorption through
      apical GLUT2.
AB  - Natural sugars and artificial sweeteners are sensed by receptors in taste buds.
      T2R bitter and T1R sweet taste receptors are coupled through G-proteins, alpha
      gustducin and transducin, to activate phospholipase C beta2 and increase
      intracellular calcium concentration. Intestinal brush cells or solitary
      chemosensory cells (SCCs) have a structure similar to lingual taste cells and
      strongly express alpha-gustducin. It has therefore been suggested over the last
      decade that brush cells may participate in sugar sensing by a mechanism analogous
      to that in taste buds. We provide here functional evidence for an intestinal
      sensing system based on lingual taste receptors. Western blotting and
      immunocytochemistry revealed that all T1R members are expressed in rat jejunum at
      strategic locations including Paneth cells, SCCs or the apical membrane of
      enterocytes; T1Rs are colocalized with each other and with alpha-gustducin,
      transducin or phospholipase C beta2 to different extents. Intestinal glucose
      absorption consists of two components: one is classical active Na+-glucose
      cotransport, the other is the diffusive apical GLUT2 pathway. Artificial
      sweeteners increase glucose absorption in the order acesulfame potassium
      approximately sucralose > saccharin, in parallel with their ability to increase
      intracellular calcium concentration. Stimulation occurs within minutes by an
      increase in apical GLUT2, which correlates with reciprocal regulation of T1R2,
      T1R3 and alpha-gustducin versus T1R1, transducin and phospholipase C beta2. Our
      observation that artificial sweeteners are nutritionally active, because they can
      signal to a functional taste reception system to increase sugar absorption during
      a meal, has wide implications for nutrient sensing and nutrition in the treatment
      of obesity and diabetes.

PMID- 17495046
TI  - Prenatal stress in the rat results in increased blood pressure responsiveness to
      stress and enhanced arterial reactivity to neuropeptide Y in adulthood.
AB  - We have shown previously that stress in the pregnant rat leads to a heightened
      cardiovascular response to restraint in adult offspring. The present study was
      undertaken to explore further the persistent cardiovascular effects of prenatal
      stress, with a focus on peripheral vascular function. Sprague-Dawley female rats
      were exposed to restraint/bright light three times daily in the last week of
      pregnancy. Litters from stressed and control females were cross-fostered to
      control dams to eliminate possible effects of maternal stress on nursing
      behaviour. At 120 days, offspring cardiovascular variables were measured by
      radiotelemetry. Reactivity of mesenteric small arteries was assessed by
      myography, and responses to electrical field stimulation determined. Resting
      cardiovascular parameters in prenatally stressed (PS) offspring were similar to
      controls but PS rats showed a greater increase in systolic blood pressure
      following restraint stress (P<0.05). Recovery was also prolonged in PS animals
      compared with controls and was of longer duration in PS females than in PS males
      (P<0.05). Adult PS females, but not males, also had elevated basal plasma
      corticosterone levels in comparison with controls (P<0.05). Vascular reactivity
      to neuropeptide Y (P<0.05) and electrical field stimulation (P<0.05) in
      mesenteric arteries was also significantly increased in PS animals. Vascular
      responses to adrenergic agonists as well as endothelial dilator function did not
      differ between PS and controls. We conclude that prenatal stress during late
      gestation has long-lasting effects on cardiovascular responsiveness and vascular
      reactivity to neuropeptide Y in the offspring.

PMID- 17495049
TI  - Proteomics analysis of human amniotic fluid.
AB  - Amniotic fluid is a dynamic and complex mixture that reflects the physiological
      status of the developing fetus. In this study, the human amniotic fluid (AF)
      proteome of a 16-18-week normal pregnancy was profiled and analyzed to
      investigate the composition and functions of this fluid. Due to the complexity of
      AF, we utilized three different fractionation strategies to provide greater
      coverage. Two types of two-dimensional LC/MS/MS as well as an LC-SDS-PAGE-LC
      MS/MS platform were used. A total of 16 AF samples between gestational ages of 16
      and 18 weeks from women carrying chromosomally normal fetuses were analyzed by
      one of the three fractionation methods followed by a common reverse phase LC
      MS/MS step. Mascot and The Global Proteome Machine engines were used to search
      the International Protein Index human database for peptide sequence
      identification. The list of proteins was generated by combining the results of
      both engines through the PeptideProphet of Scaffold software. All identified
      proteins were combined to generate the AF proteome comprising 1,026 unique gene
      matches or 842 non-redundant proteins. This list includes most of the currently
      used biomarkers for pregnancy-associated pathologic conditions such as preterm
      delivery, intra-amniotic infection, and chromosomal anomalies of the fetus. The
      subcellular localization, tissue expression, functions, and networks of the AF
      proteome were analyzed by various bioinformatic tools. These data will contribute
      to the better understanding of amniotic fluid function and to the discovery of
      novel biomarkers for prenatal diagnosis of fetal abnormalities.

PMID- 17495047
TI  - Age-related physiological and morphological changes of muscle spindles in rats.
AB  - Age-related physiological and morphological changes of muscle spindles were
      examined in rats (male Fischer 344/DuCrj: young, 4-13 months; middle-aged, 20-22
      months; old, 28-31 months). Single afferent discharges of the muscle spindles in
      gastrocnemius muscles were recorded from a finely split dorsal root during ramp
      and-hold (amplitude, 2.0 mm; velocity, 2-20 mm s(-1)) or sinusoidal stretch
      (amplitude, 0.05-1.0 mm; frequency, 0.5-2 Hz). Respective conduction velocities
      (CVs) were then measured. After electrophysiological experimentation, the muscles
      were dissected. The silver-impregnated muscle spindles were teased and then
      analysed using a light microscope. The CV and dynamic response to ramp-and-hold
      stretch of many endings were widely overlapped in old rats because of the
      decreased CV and dynamic response of primary endings. Many units in old rats
      showed slowing of discharge during the release phase under ramp-and-hold stretch
      and continuous discharge under sinusoidal stretch, similarly to secondary endings
      in young and middle-aged rats. Morphological studies revealed that primary
      endings of aged rat muscle spindles were less spiral or non-spiral in appearance,
      but secondary endings appeared unchanged. These results suggest first that
      primary muscle spindles in old rats are indistinguishable from secondary endings
      when determined solely by previously used physiological criteria. Secondly, these
      physiological results reflect drastic age-related morphological changes in
      spindle primary endings.

PMID- 17495048
TI  - Disinhibition of perifornical hypothalamic neurones activates noradrenergic
      neurones and blocks pontine carbachol-induced REM sleep-like episodes in rats.
AB  - Studies in behaving animals suggest that neurones located in the perifornical
      (PF) region of the posterior hypothalamus promote wakefulness and suppress sleep.
      Among such cells are those that synthesize the excitatory peptides, orexins
      (ORX). Lack of ORX, or their receptors, is associated with narcolepsy/cataplexy,
      a disorder characterized by an increased pressure for rapid eye movement (REM)
      sleep. We used anaesthetized rats in which pontine microinjections of a
      cholinergic agonist, carbachol, can repeatedly elicit REM sleep-like episodes to
      test whether activation of PF cells induced by antagonism of endogenous, GABA(A)
      receptor-mediated, inhibition suppresses the ability of the brainstem to generate
      REM sleep-like state. Microinjections of the GABA(A) receptor antagonist,
      bicuculline (20 nl, 1 mm), into the PF region elicited cortical and hippocampal
      activation, increased the respiratory rate and hypoglossal nerve activity,
      induced c-fos expression in ORX and other PF neurones, and increased c-fos
      expression in pontine A7 and other noradrenergic neurones. The ability of pontine
      carbachol to elicit any cortical, hippocampal or brainstem component of the REM
      sleep-like response was abolished during the period of bicuculline-induced
      activation. The activating and REM sleep-suppressing effect of PF bicuculline was
      not attenuated by systemic administration of the ORX type 1 receptor antagonist,
      SB334867. Thus, activation of PF neurones that are endogenously inhibited by
      GABA(A) receptors is sufficient to turn off the brainstem REM sleep-generating
      network; the effect is, at least in part, due to activation of pontine
      noradrenergic neurones, but is not mediated by ORX type 1 receptors. A
      malfunction of the pathway that originates in GABA(A) receptor-expressing PF
      neurones may cause narcolepsy/cataplexy.

PMID- 17495050
TI  - Molecular mechanisms underlying anti-inflammatory phenotype of neonatal splenic
      macrophages.
AB  - Neonatal humans and rodents are susceptible to infection with encapsulated
      bacteria as a result of an inability to make antibodies to capsular
      polysaccharides. This is partly a result of decreased production of
      proinflammatory cytokines by splenic macrophages (MPhi) from neonates. In this
      study, we show that when stimulated with a variety of agonists to TLR2, -4, and 
      9, neonatal MPhi make less proinflammatory cytokines and more IL-10 than adult
      MPhi. IL-10 appears to have a role in the decreased proinflammatory cytokine
      production, as neonatal MPhi treated with anti-IL-10 receptor antibody or from IL
      10(-/-) mice produced levels of proinflammatory cytokines at a level comparable
      with that produced by adult MPhi. A microarray analysis of RNA from resting and
      LPS-stimulated MPhi from neonatal and adult mice showed that expression of a
      large number of genes encoding cytokines, chemokines, and their receptors was
      decreased dramatically in the neonatal MPhi, although some cytokines, including
      IL-10 and IL-16, were enhanced. Several genes in the TLR signaling pathway
      leading to NF-kappaB activation were down-regulated, which may account for the
      decreased chemokine and cytokine synthesis. It is surprising that p38alpha MAPK,
      known to be required for TLR-induced cytokine secretion, was enhanced in the
      neonatal MPhi. Our studies with the p38 MAPK inhibitor SB203580 suggested that
      excess p38 MAPK activity can be inhibitory for TLR2-, -4-, and -9-induced
      production of proinflammatory cytokines but not IL-10. The anti-inflammatory
      phenotype of the neonatal Mphi may be unique to the developing organism, although
      it compromises the neonate's ability to respond to encapsulated bacteria.

PMID- 17495051
TI  - Pivotal advance: endogenous pathway to SIRS, sepsis, and related conditions.
AB  - TLRs are usually thought to recognize substances produced by microorganisms and
      thus, to initiate host defenses. This concept, however, fails to explain some
      functions of this family of receptors. Recognition of endogenous substances may
      explain the broader functions of TLRs in physiology and disease. Activation of
      TLRs by endogenous substances necessitates vigorous control of the function of
      the receptors. This communication will summarize a line of research, which points
      to an endogenous agonist for TLR4 and a putative mechanism for controlling the
      function of that receptor.

PMID- 17495052
TI  - Percutaneous transluminal angioplasty using a pull-through technique for hepatic
      arterial occlusion at the time of port-catheter implantation.
AB  - We report a successful percutaneous transluminal angioplasty using a pull-through
      technique for the treatment of a hepatic arterial occlusion caused by iatrogenic
      subintimal dissection during the percutaneous placement of a port-catheter
      system.

PMID- 17495053
TI  - Differentiated thyroid cancer presenting with thyrotoxicosis due to functioning
      metastases.
AB  - Thyrotoxicosis due to functioning metastases in differentiated thyroid cancer
      (DTC) is exceedingly rare. We report a case of follicular carcinoma in a 54-year
      old manager, who presented with thyrotoxicosis, shortness of breath and lung
      metastases. Transbronchial biopsy of a pulmonary nodule demonstrated normal
      thyroid. This was interpreted as representing very well-differentiated thyroid
      cancer. CT, (131)I whole-body imaging and dosimetry is described following total
      thyroidectomy and repeated radioiodine administration (cumulative activity 34.6
      GBq). The patient became asymptomatic with almost complete eradication of the
      pulmonary metastases. Potential complications of thyroid storm, bone marrow
      failure and pulmonary fibrosis following radioiodine are discussed, together with
      methods to minimise these risks.

PMID- 17495054
TI  - A giant malignant peripheral nerve sheath tumour of the breast: CT and
      pathological findings.
AB  - Malignant peripheral nerve sheath tumour (MPNST) is a rare soft tissue sarcoma.
      In particular, primary MPNST of the breast is extremely rare. We report a case of
      a giant malignant peripheral nerve sheath tumour involving the entire right
      breast, which was not associated with neurofibromatosis type 1 (NF-1) or previous
      radiation therapy. A CT scan showed a huge heterogeneous soft tissue mass with
      well-enhanced nodules at its periphery and low-density internal necrosis, which
      was confirmed by modified radical mastectomy.

PMID- 17495055
TI  - Candida inferior vena cava filter infection and septic thrombophlebitis.
AB  - Candida infection following central venous catheterization (CVC) is a well known
      complication, most common infection being that caused by Candida albicans. Less
      common is infection with Candida glabrata. Candida septic thrombophlebitis of the
      central veins is an uncommon complication after CVC. We report the first case of
      inferior vena cava filter infection with C. glabrata following septic
      thrombophlebitis of the femoral veins and discuss management of this rare
      complication.

PMID- 17495056
TI  - Cardiac metastasis: a cause of recurrent pulmonary emboli.
AB  - Intracavitary cardiac metastasis is rare. Apart from causing intracardiac
      obstruction, this type of metastasis can present as pulmonary emboli. It is
      important to suspect this diagnosis in an oncology patient with recurrent
      pulmonary emboli, particularly in the setting of a negative venous Doppler
      ultrasound of the lower limbs and pelvis. Early recognition may help in improving
      the prognosis. We present a case of intracavitary cardiac metastasis arising from
      a squamous carcinoma of the cervix, in a patient with recurrent pulmonary tumour
      emboli.

PMID- 17495057
TI  - Transcatheter arterial embolisation of a ruptured pseudoaneurysm of the lingual
      artery with n-butyl cyanoacrylate.
AB  - Pseudoaneurysms can arise due to localized arterial wall disruption, owing to
      various factors such as inflammation, trauma, neoplasm, or surgical procedures.
      Once ruptured, bleeding can be life-threatening. Thus, a treatment for
      pseudoaneurysm is necessary. We describe a case of post-surgical ruptured
      pseudoaneurysm of the lingual artery that was successfully treated by
      transcatheter embolisation with n-butyl cyanoacrylate (NCBA).

PMID- 17495058
TI  - Renal artery embolisation in the palliative treatment of renal carcinoma.
AB  - The aim of this study is to review the role and technique of renal artery
      embolisation (RAE), and assess its effectiveness in the palliative treatment of
      unresectable or inoperable renal cell carcinoma (RCC) in our institution. The
      study group consisted of 19 consecutive patients (16 male, 3 female; age range 47
      87 years) who underwent palliative RAE for the treatment of renal carcinoma
      between January 2000 and December 2005. Unresectable disease was present in 11
      patients (3 stage IVa, 8 stage IVb). Potentially resectable disease was present
      in 8 patients (4 stage II, 1 stage IIIa, 1 stage IIIb, 2 stage IIIc); however,
      these patients were unfit for surgery for other reasons. 13 patients presented
      with haematuria, which was gross in 7 patients. Nine patients complained of flank
      pain. RAE was performed using polyvinyl alcohol or embosphere particles, metallic
      coils and, in some cases, absolute alcohol was necessary. At the time of
      analysis, 12 patients had died while 7 patients were still alive, with an overall
      median survival for the study group of 6 months. In the 7 patients with
      transfusion dependant gross haematuria, there was stabilization of the
      haemoglobin level post-embolisation. In the 9 patients who presented with flank
      pain, symptoms improved or resolved in 8 patients. The median length of hospital
      stay for the 18 patients who were discharged was 5.0 days. RAE is a safe and
      tolerable management option for patients with inoperable or unresectable renal
      carcinoma as a means of palliation of local symptoms and improving clinical
      status, with low morbidity and shorter hospital stay.

PMID- 17495059
TI  - The double wire technique: an improved method for treating challenging
      ureteroileal anastomotic strictures and occlusions.
AB  - Up to 10% of patients who undergo ileal conduit urinary diversion may go on to
      develop ureteroileal anastomotic stenosis (UIAS); this can lead to recurrent
      urinary tract infections and deterioration in renal function. Classical
      management has been open revision of the anastomosis. We describe a novel
      technique that allows balloon dilatation and ureteral stent placement in a
      retrograde fashion. All patients in this study had undergone radical cystectomy
      and ileal conduit formation with Wallace type end-to-end refluxing uretero
      intestinal anastomosis. After initial retrograde loopogram, a 6F MPA-1 catheter
      and an 0.035 inch extra stiff guide was passed to the distal ostium.
      Subsequently, a customised 8F bright tip MPA-1 guiding catheter was advanced over
      the guide wire which allowed effective splinting of the equipment to facilitate
      greater control of a second catheter and guide wire combination to access the
      stenotic or occluded anastomosis. Results show that a total of ten anastomoses
      were treated; nine anastomoses were successfully treated with a primary
      retrograde approach with no intra or post-procedural complications. After a mean
      follow-up of 19 months (5-33 months), as assessed by ascending loopograms, all
      anastomoses remained open. In conclusion, morbidity of open surgery has resulted
      in the popularization of endourological techniques in treating anastomotic
      stenoses. However, key to these endourological techniques is access to the
      anastomosis; typically, this has been via a percutaneously placed nephrostomy.
      The ideal route to the anastomosis is via a retrograde approach; we have
      illustrated a safe and successful novel technique that utilized two guidewires
      and a guiding catheter, allowing retrograde ureteral access.

PMID- 17495060
TI  - Awareness of making the best use of a Department of Clinical Radiology amongst
      physicians in Leeds Teaching Hospitals, UK.

PMID- 17495061
TI  - Relative biological effectiveness and exposure of the female breast.

PMID- 17495062
TI  - Abdominal distension 3 days post-high-speed road traffic accident.

PMID- 17495063
TI  - Helmets for skiers and snowboarders: an injury prevention program.
AB  - The authors' Level I trauma center has advocated the use of ski helmets for
      several years and in 1998, undertook a social-marketing campaign and a helmet
      loaner program to increase helmet use among skiers and snowboarders. The loaner
      program's effect on helmet acceptance was measured by comparing helmet acceptance
      in participating rental stores with acceptance in nonparticipating stores during
      3 years. For the 1998-1999 season, 13.8% of renters in the participating stores
      accepted a helmet compared to 1.38% in the nonparticipating stores (p < .01); for
      2000-2001, 33.5% to 3.93% (p < .01); and for 2001-2002, 30.3% to 4.48% (p < .01).
      The authors believe that efforts to increase helmet use--by increasing education
      and public awareness and decreasing barriers, such as through helmet loaner
      programs or routinely including helmets in rental packages--have significant
      potential to decrease the incidence and severity of brain injuries from skiing
      and/or snowboarding accidents in Colorado.

PMID- 17495071
TI  - Up-regulation and increased activity of KV3.4 channels and their accessory
      subunit MinK-related peptide 2 induced by amyloid peptide are involved in
      apoptotic neuronal death.
AB  - The aim of the present study was to investigate whether K(V)3.4 channel subunits
      are involved in neuronal death induced by neurotoxic beta-amyloid peptides
      (Abeta). In particular, to test this hypothesis, three main questions were
      addressed: 1) whether the Abeta peptide can up-regulate both the
      transcription/translation and activity of K(V)3.4 channel subunit and its
      accessory subunit, MinK-related peptide 2 (MIRP2); 2) whether the increase in
      K(V)3.4 expression and activity can be mediated by the nuclear factor-kappaB (NF
      kappaB) family of transcriptional factors; and 3) whether the specific inhibition
      of K(V)3.4 channel subunit reverts the Abeta peptide-induced neurodegeneration in
      hippocampal neurons and nerve growth factor (NGF)-differentiated PC-12 cells. We
      found that Abeta(1-42) treatment induced an increase in K(V)3.4 and MIRP2
      transcripts and proteins, detected by reverse transcription-polymerase chain
      reaction and Western blot analysis, respectively, in NGF-differentiated PC-12
      cells and hippocampal neurons. Patch-clamp experiments performed in whole-cell
      configuration revealed that the Abeta peptide caused an increase in I(A) current
      amplitude carried by K(V)3.4 channel subunits, as revealed by their specific
      blockade with blood depressing substance-I (BDS-I) in both hippocampal neurons
      and NGF-differentiated PC-12 cells. The inhibition of NF-kappaB nuclear
      translocation with the cell membrane-permeable peptide SN-50 prevented the
      increase in K(V)3.4 protein and transcript expression. In addition, the SN-50
      peptide was able to block Abeta(1-42)-induced increase in K(V)3.4 K(+) currents
      and to prevent cell death caused by Abeta(1-42) exposure. Finally, BDS-I produced
      a similar neuroprotective effect by inhibiting the increase in K(V)3.4
      expression. As a whole, our data indicate that K(V)3.4 channels could be a novel
      target for Alzheimer's disease pharmacological therapy.

PMID- 17495072
TI  - The global importance of poultry.

PMID- 17495073
TI  - Effect of chronic heat exposure on fat deposition and meat quality in two genetic
      types of chicken.
AB  - The effects of chronic heat stress on growth, proportion of carcass and fat
      deposition, and meat quality were investigated in 2 genetic types of chickens.
      One hundred and eight 5-wk-old male chickens from a commercially fast-growing
      strain (Arbor Acres, AA) and a locally slow-growing species (Beijing You chicken,
      BJY) were kept in the following conditions: constant optimal ambient temperature
      at 21 degrees C and ad libitum feeding (21AL), constant high ambient temperature
      at 34 degrees C and ad libitum feeding (34AL), and constant optimal ambient
      temperature 21 degrees C and pair-fed to the 34AL chickens (21PF). The results
      showed that feed intakes were decreased by heat exposure in both type of chickens
      at 8 wk of age (P<0.001). At 34 degrees C, AA broilers exhibited greatly
      decreased weight gain (22.38 vs. 61.45 g/d for 21AL) and lower breast proportion
      compared with 21AL, while the relevant indices of BJY chickens were not affected
      in hot condition. Abdominal fat deposition of BJY chickens was enhanced by heat
      exposure (P<0.05). Fat deposition of AA broilers was decreased in heat-exposed
      and pair-fed chickens. Abdominal and intermuscular fat deposition in 34AL birds,
      however, were enhanced compared with 21PF birds (P<0.01). The L* values, drip
      loss, initial pH, and shear force of breast meat in BJY chickens were not
      affected by treatments. In AA birds, chronic heat stress increased L* values and
      drip loss compared with 21AL, but pH and shear force were not affected by
      treatments. The results from this study indicated that the impact of heat stress
      was breed dependent and that BJY chickens showed higher resistance to high
      ambient temperature, which could be related to their increased feed efficiency
      and deposition of abdominal fat under heat exposure.

PMID- 17495074
TI  - Stress in broilers resulting from shackling.
AB  - The aim of this study was to assess stress response of broilers to different
      periods of shackling. Stress effects of shackling were monitored in a group of
      male Ross 308 broilers (total number: 400) aged 42 d. Three shackling treatments
      were used in our experiment: shackling of broilers for 30 s (group T30), 60 s
      (group T60), and 120 s (group T120). Corticosterone plasma concentration was
      elevated in T60 broilers (P<0.05) and in T120 birds (P<0.01); glucose plasma
      concentration was increased (P<0.05) in both T60 and T120 broilers when compared
      with nonshackled control. Lactate concentrations increased in T30 birds (P<0.05)
      and in both T60 and T120 birds (P<0.01). Furthermore, T120 broilers exhibited an
      increase (P<0.01) in heterophil counts and heterophil:lymphocyte ratio. Duration
      of tonic immobility was increased (P<0.05) in T60 and T120 broilers. Number of
      attempts to induce tonic immobility decreased (P<0.01) in all test groups (T30,
      T60, T120). Duration of shackling period was positively correlated (P<0.001) with
      corticosterone, glucose and lactate level, tonic immobility duration, and
      heterophil:lymphocyte ratio. The number of inductions was negatively correlated
      (P<0.001) with duration of the shackling period. According to the results of our
      study, the act of shackling is a considerable traumatic procedure for broilers,
      and its stress effect is markedly dependent on duration of shackling period that
      the broiler chickens experience. It follows from our study that the optimal
      shackling period should be less than 60 s.

PMID- 17495075
TI  - Effects of purified lignin and mannan oligosaccharides on intestinal integrity
      and microbial populations in the ceca and litter of broiler chickens.
AB  - A study was conducted to evaluate lignin and mannan oligosaccharides as potential
      alternatives to antibiotic growth promoters in broilers. Dietary treatments
      included an antibiotic-free diet (CTL-), a positive control (CTL+, 11 mg/kg of
      virginiamycin), and an antibiotic-free diet containing BioMos (MOS, 0.2% to 21 d
      and 0.1% thereafter) or Alcell lignin at 1.25% (LL) or 2.5% (HL) of the diet.
      Each treatment was randomly assigned to 4 floor pen replicates (40 birds each).
      Body weight and feed conversion were recorded weekly throughout 42 d. Jejunum
      histology was analyzed at d 14, 28, and 42. At d 28 and 42, cecal contents were
      assayed for Escherichia coli, Salmonella, lactobacilli, and bifidobacteria, and
      the litter was analyzed for E. coli and Salmonella. Birds fed the CTL- diet were
      heavier (P<0.05) than those fed the other dietary treatments, but feed conversion
      was not affected by dietary treatments. Birds fed MOS and LL had increased
      jejunum villi height and a higher number of goblet cells per villus (P<0.05) when
      compared with those fed the CTL+ diet. At d 42, birds fed MOS, LL, or HL had
      greater lactobacilli numbers than those fed the CTL+ diet. Compared with the CTL+
      diet, the MOS diet increased the populations of bifidobacteria (P<0.05) in the
      ceca. Litter E. coli load was lower in birds fed MOS (P<0.05) than in birds fed
      the CTL+ diet but comparable to that of birds fed the LL or HL diet. Broiler
      performance was similar in birds fed antibiotics or antibiotic-free diets
      containing either MOS or lignin. However, birds fed MOS and LL had a comparative
      advantage over birds fed antibiotics as evidenced by an increased population of
      beneficial bacteria in the ceca, increased villi height and number of goblet
      cells in the jejunum, and lower population of E. coli in the litter.

PMID- 17495076
TI  - Identification of Avai polymorphisms in the third intron of GH gene and their
      associations with abdominal fat in chickens.
AB  - Growth hormone (GH) plays a diverse role in animals together with other hormones
      of somatotropic axis. In the current research, chicken GH (cGH) as a candidate
      gene affecting carcass traits was investigated in the chickens from 2 local
      chicken breeds [Mountainous Black-Bone (Wugu) and Caoke chicken] in the Sichuan
      province, 1 pure line of a quality chicken (Sanhuang chicken) from the Guangdong
      province, and commercial crossbreds. The RFLP method was used to identify
      polymorphisms of the cGH gene. Three restriction enzyme polymorphic sites were
      detected in the cGH gene. Sequence alignment from GenBank revealed 2 mutations in
      the third intron of the cGH gene, which were identified by the AvaI enzyme. Two
      novel AvaI polymorphic sites were genotyped in 240 chickens from the above
      mentioned chicken populations. One EcoRV polymorphic site, the previously
      reported polymorphism, was also detected in these populations. Significant
      differences in allelic and genotypic frequencies among all the chicken
      populations were observed. In AvaI polymorphic sites, allele A2 and B1 had higher
      frequencies than allele A1 and B2, respectively. In EcoRV polymorphic sites, the
      frequency of allele N2 was higher than that of allele N1. Associations of
      polymorphisms of the cGH gene with carcass traits were analyzed by using a GLM
      procedure. Significant associations were found between AvaI genotypes or combined
      genotypes and abdominal fat weight and abdominal fat percentage (P<or=0.05). The
      allele A2 and B1 had a beneficial effect on increasing the live BW, breast muscle
      weight, and breast muscle percentage while decreasing the abdominal fat weight,
      abdominal fat percentage, and s.c. fat thickness. No significant associations
      were observed between EcoRV genotypes and carcass traits. In conclusion, the cGH
      gene may be a potential marker affecting the abdominal fat trait of chickens.

PMID- 17495077
TI  - Mapping quantitative trait loci affecting body weight and abdominal fat weight on
      chicken chromosome one.
AB  - Body weight and abdominal fat traits are complex and important economic traits
      that may benefit from the implementation of MAS. The objective of the current
      study was to identify QTL associated with BW and abdominal fat traits. The
      Northeast Agricultural University resource population was used in the current
      study. Body weight and abdominal fat weight were measured in the F2 population. A
      total of 369 F2 individuals produced from 4 F1 families, their parents, and F0
      birds were genotyped by 23 fluorescent microsatellite markers on chromosome 1. A
      linkage map was constructed, and interval mapping was conducted to identify
      putative QTL. For BW, 10 QTL were identified at the 1% chromosome wide level, and
      these 10 QTL were grouped to 3 different regions; 2 QTL were identified at the 5%
      chromosome wide level, and these 2 QTL were grouped to 2 different regions; and 5
      QTL were identified at the suggestive level, and these 5 QTL were grouped to 4
      different regions. For the abdominal fat traits, 1 QTL was identified at the 1%
      chromosome wide level, 1 QTL was identified at the 5% chromosome wide level, and
      2 QTL were identified at the suggestive level. The QTL for BW at 12 wk of age
      explained 13.51% of the phenotypic variance, and 2 QTL for abdominal fat weight
      explained 2.53 and 3.97% of the phenotypic variance, respectively. The present
      study identified chromosome regions harboring significant QTL affecting BW and
      abdominal fat traits. The results provide a useful reference for further
      candidate gene research and MAS for BW and abdominal fat traits.

PMID- 17495078
TI  - Natural humoral immune competence and survival in layers.
AB  - The relation between survival and levels of humoral components of innate (and
      specific) immune competence of laying hens was investigated in a population of
      1,063 laying hens from 12 purebred layer lines. Natural immune competence of the
      chickens was studied by measuring levels of natural antibodies (NAb) binding to
      keyhole limpet hemocyanin (KLH) or lipopolysaccharide (LPS), respectively, and
      hemolytic (classical and alternative) complement activity at 20, 40, and 65 wk of
      age. In addition, levels of antibodies binding a Newcastle disease vaccine strain
      as a measure of specific immunity were investigated at 20 wk of age. A
      distinction could be made between lines showing high or low immune competence
      with respect to NAb, complement activity, and specific antibodies. Within lines,
      significant correlations were found for each of the innate parameters among the 3
      ages. The innate and specific parameters were, however, not correlated with each
      other. Based on the limited data set, it was not possible to draw conclusions on
      line differences for innate or specific immune competence in relation to
      survival. However, regardless of line, low levels of NAb binding to KLH or high
      levels of NAb binding to LPS were detected in chickens that did not survive the
      laying period. The major difference between the responses of NAb binding to KLH
      or LPS was that the chickens probably did not encounter KLH, which suggests a
      reflection of the capacity to respond, whereas the chickens most probably did
      encounter LPS, which suggests a reflection of the active status of the innate
      humoral immune system. In conclusion, we propose that levels (KLH) and activation
      (LPS) of components of natural antibodies are indicative for the probability that
      chickens survive a laying period.

PMID- 17495079
TI  - Direct-fed microbial PrimaLac and salinomycin modulate whole-body and intestinal
      oxygen consumption and intestinal mucosal cytokine production in the broiler
      chick.
AB  - The current study investigated whole-body O2 consumption, intestinal O2
      consumption, and intestinal inflammation status through mucosal cytokine
      production on broiler chicks fed the direct-fed microbial PrimaLac. One hundred
      twenty 1-d-old broiler chicks were randomly assigned to 1 of 3 experimental
      diets: standard starter diet (control), standard starter diet with added
      salinomycin (SAL), and standard starter diet with added PrimaLac (DFM). Birds
      were housed in 2 separate rooms, the control and SAL treatments in one room and
      the DFM in another. Intact ileal and cecal samples were collected on d 19, 20,
      and 21 after measuring whole-body O2 consumption using indirect calorimetry. The
      O2 up-take of ileal tissue was measured using an in vitro O2 monitor. Analysis of
      intestinal immune status of broilers was measured by the relative differences in
      mRNA of both pro- and antiinflammatory cytokines: interleukin-(IL) 1beta, IL-6,
      and IL-10 using real-time reverse transcription-PCR. Broilers exhibited a 6 to
      16% decrease in whole-body energy expenditures and up to a 47% decrease (P<0.05)
      in ileal energy expenditures in the DFM group compared with other treatments. The
      reverse transcription-PCR data demonstrated that DFM consortium numerically
      altered both pro- and antiinflammatory cytokines within the ileum of 19-d
      posthatch broilers. These data suggest that direct-fed microbials like PrimaLac
      increase metabolic efficiency via changes in intestinal physiology and
      metabolism.

PMID- 17495081
TI  - Use of guar by-products in high-production laying hen diets.
AB  - A 5x5 Latin square experiment was conducted to evaluate the effect of feeding low
      concentrations of guar germ or a combination of guar germ and hull (guar meal) in
      high-production laying hen diets. A total of 125 Lohmann laying hens (21 wk old)
      of similar BW were randomly assigned to 5 blocks. Each block was divided into 5
      experimental units, consisting of 5 hens per unit. Hens were fed either a nonguar
      control diet, or 1 of 4 diets containing either 2.5 or 5% guar germ, or 2.5 or 5%
      guar meal over a 20-wk trial period (five 4-wk periods). No significant
      differences were observed when feeding either 2.5 or 5% guar germ or meal
      (P>0.05) on hen-day egg production or feed consumption. Significant differences
      in egg weight, total egg mass per hen, and feed conversion ratio were detected in
      hens fed 2.5% guar meal, whereas they remained unchanged for diets containing
      either level of guar germ or 5% guar meal. Feeding either level of guar germ or
      guar meal did not affect shell quality (shell thickness, egg breaking force, and
      specific gravity), Haugh units, or egg yolk color (L*, a*, b*). The results
      showed that both guar germ and guar meal can be fed to high-production laying
      hens at up to 5% without adverse effects on laying hen performance.

PMID- 17495080
TI  - Effects of chito-oligosaccharide supplementation on performance, nutrient
      digestibility, and serum composition in broiler chickens.
AB  - A total of 196 day-old male broiler chicks were randomly allocated to 1 of 4
      treatments in a study conducted to determine the effects of dietary
      supplementation of chito-oligosaccharide (COS) on growth, nutrient digestibility,
      and serum composition. The experimental diets consisted of an unsupplemented
      control diet based on corn, soybean meal, and fish meal or similar diets
      supplemented with either chlortetracycline, 50 mg/kg of COS, or 100 mg/kg of COS.
      Each treatment was fed to 7 replicate pens of birds, with 7 birds per pen.
      Broiler performance, nutrient digestibility, cecal microbial concentrations, and
      serum indices were measured at the end of the starter (d 21) and grower phases (d
      42). During the starter period and overall, broilers fed 50 or 100 mg/kg of COS
      had better (P<0.05) average daily gain, average daily feed intake, and feed
      conversion than the control birds. The performance of birds fed chlortetracycline
      was generally intermediate between that of the control and the 2 COS treatments.
      Compared with the birds in the control or chlortetracycline treatments, the birds
      receiving 100 mg/kg of COS had better nutrient digestibility of DM, energy,
      calcium, and phosphorus; higher (P<0.05) concentrations of cecal Lactobacillus;
      and lower (P<0.05) serum triglyceride and total cholesterol during the starter
      phase. During the grower phase, the birds fed 100 mg/kg of COS had higher
      (P<0.05) calcium digestibility and CP retention than those fed the
      chlortetracycline treatment, and lower concentrations of cecal Escherichia coli
      than birds in the control treatment. The serum growth hormone level in birds fed
      50 mg/kg of COS was higher (P<0.05) than in the other treatments. The birds fed
      100 mg/kg of COS had lower (P<0.05) serum triglyceride, higher (P<0.05) serum
      high-density lipoprotein cholesterol, and higher serum total protein content than
      birds in the other treatments. In conclusion, dietary supplementation with COS
      appeared to improve the average daily gain of broilers by increasing the average
      daily feed intake and nutrient digestibility and modulating the concentrations of
      cecal microbial flora. Additionally, COS increased serum protein and high-density
      lipoprotein cholesterol and decreased serum triglyceride.

PMID- 17495082
TI  - Microarchitecture and spatial relationship between bacteria and ileal, cecal, and
      colonic epithelium in chicks fed a direct-fed microbial, PrimaLac, and
      salinomycin.
AB  - Direct-fed microbials (DFM) could serve as a potential alternative to the feeding
      of antibiotics in poultry production. In this study, the effects of providing a
      DFM were compared with the feeding of salinomycin on intestinal
      histomorphometrics, and microarchitecture was examined. Broiler chicks (n=18 per
      treatment; trials 1 and 2) were fed a standard starter diet (control),
      control+PrimaLac (DFM; 0.3% wt/wt), and control+salinomycin (SAL; 50 ppm) from
      hatch to 21d. The birds were euthanized on d 21, and the ileal, jejunal, cecal,
      and colon tissues were dissected. Samples were examined by light microscopy
      (jejunum and ileum; trial 1) and scanning electron microscopy (ileum, cecum, and
      colon; trial 2). Feeding of the DFM increased intestinal muscle thickness
      (P<0.05) up to 33% compared with the control treatment. The DFM group also had
      increased villus height and perimeter (P=0.009 and 0.003, respectively) in
      jejunum. Segmented filamentous-like bacteria were less numerous in DFM-treated
      chicks than in the control chicks. Very few segmented filamentous-like bacteria
      were found near other microbes in the ileum. The DFM chicks had a larger number
      of bacteria positioned over or near goblet cells and in intervilli spaces.
      Bacteria in the colon were observed to be attached primarily around and within
      the crypts. Mucous thickness was less, and the density of bacteria embedded in
      the mucous blanket appeared to be lower in DFM-treated animals than in the
      control in all intestinal segments. The birds fed SAL had fewer bacteria and
      enterocytes in the ileum than in the control-and DFM-treated birds, and they had
      thicker and fewer microvilli. Because gastrointestinal track colonization by the
      DFM organisms can prevent the attachment of pathogens to the epithelium, spatial
      relationships, in this study, demonstrate the functionality of DFM and probiotics
      in preventing disease. It also supports previous observations that the feeding of
      salinomycin may alter intestinal function.

PMID- 17495083
TI  - Effect of a kestose and nystose preparation on growth performance and
      gastrointestinal tract function of turkeys.
AB  - The aim of the present study was to determine the effects of dietary
      administration of a fructooligosaccharide preparation rich in kestose and nestose
      on growth performance and gastrointestinal parameters in young turkeys. The
      kestose and nestose preparation was obtained through bioconversion of sucrose
      using fungi fructosyl transferase and contained in DM 39.9% of kestose, 17.6% of
      nystose, as well as 26.5% of glucose and 14.7% of sucrose. Three dietary levels
      of the sum of kestose and nystose (0.3, 0.6, and 1.2%) were fed to growing
      turkeys for 8 wk. When compared with the control treatment, addition of the
      kestose and nestose preparation had no effect on feed intake, feed conversion,
      and BW. The kestose and nestose-supplemented diet, especially the medium level of
      kestose and nystose, influenced microbial metabolism, especially in the ceca.
      Compared with the control group, the medium level of kestose and nestose
      decreased relative weight of gizzard (from 18.67 to 16.51 g/kg of BW) and weight
      of small intestine tissue (from 23.3 to 19.6 g/kg of BW) and increased weight of
      ceca digesta (from 3.51 to 4.77 g/kg of BW) as well as activities of microbial
      beta-glucosidase (an increase from 0.22 to 0.38 U/g) and alpha-galactosidase (an
      increase from 0.90 to 1.61 U/g), pH of digesta (a decrease from 6.13 to 5.79),
      concentration of NH3 (an increase from 0.60 to 0.98 mg/g), and concentration of
      total short-chain fatty acids (an increase from 81.1 to 107.7 micromol/g) in the
      cecal digesta. A high content of kestose and nestose in the diet caused a
      decrease in ileal and cecal pH (to 5.42 and 5.49, respectively).

PMID- 17495084
TI  - Threonine requirement of slow-growing male chickens depends on age and dietary
      efficiency of threonine utilization.
AB  - Nitrogen-balance experiments were conducted with a total of 288 male chickens to
      assess Thr requirement data on 2 commercial slow-growing genotypes (I 657 and Red
      JA from Hubbard ISA) by use of a modeling procedure described previously. Six
      graded levels of dietary protein supply from high-protein soybeanmeal were used
      within 4 age periods (period I: 10 to 25 d; period II: 30 to 45 d; period III: 5
      to 65 d; and period IV: 70 to 85 d). The provided dietary amino acid ratio
      (Lys:Met+Cys:Thr=1:0.85:0.54), with 3.87% Thr in the feed protein, identified Thr
      as the first limiting dietary amino acid. The nitrogen maintenance requirement
      (NMR) was established by exponential approximation of N excretion depending on N
      intake (on average, NMR=173 mg of N/BWkg0.67 per d). The theoretical maximum for
      daily N deposition was estimated by the Levenberg-Marquardt algorithm (SPSS
      program, version 11.5) and by exponential fitting of N balance data depending on
      N intake. The observed dietary Thr efficiency was used to model Thr requirements
      for a given protein deposition depending on age. The optimal dietary Thr
      concentration (percentage of feed) was established by different predictions for
      daily feed intake. Daily CP deposition of approximately 60% of the potential
      required 0.83 and 0.87% (10 to 25 d), 0.73 and 0.75% (30 to 45 d), 0.66 and 0.69%
      (50 to 65 d), and 0.51 and 0.53% (70 to 85 d) of Thr in feed for genotype I 657
      and genotype Red JA, respectively (average daily feed intakes of 30, 75, 100, and
      100 g in age periods I to IV). Results of model calculations need verification in
      comparative growth studies with assessment of nutrient deposition and varying
      dietary Thr efficiencies.

PMID- 17495085
TI  - Effects of fermented soybean meal on digestive enzyme activities and intestinal
      morphology in broilers.
AB  - The experiment was performed to compare the effects of fermented soybean meal
      (fermented with Aspergillus oryzae 3.042, FSBM) and soybean meal on digestive
      enzyme activities and intestinal morphology in broilers. Three hundred twenty 1-d
      old Ross x Ross male broiler chicks were randomly allocated into 2 dietary
      treatments for a 6-wk feeding trial, including 0- to 21-d and 21- to 42-d
      periods. At the end of each stage, 8 broilers of each treatment were killed, and
      pancreas, small intestine digesta, and duodenum, jejunum, and ileum segments were
      collected for digestive enzymes and intestinal morphology evaluation. Results of
      the experiment showed that replacing soybean meal with FSBM in diet increased the
      activities of trypsin, lipase, and protease significantly in intestinal content
      of starter broilers (P<0.05) and enhanced the protease activity of grower
      broilers (P<0.05). Amylase activity was not affected in both feeding periods by
      the treatments. Compared with the control, broilers fed with FSBM had lower
      pancreatic trypsin activity (P<0.05) in the starter phase. There were no
      significant differences on lipase, amylase, and protease activity between the
      treatments in both growth phases. Increased villus height (P<0.05) and decreased
      crypt depth (P<0.05) of jejunum mucosa could be observed in the whole growth
      stage of broilers fed with FSBM. Also, duodenal villus height of starter chicks
      was also significantly increased (P<0.05).

PMID- 17495086
TI  - Dose-dependent effects of T-2 toxin on performance, lipid peroxidation, and
      genotoxicity in broiler chickens.
AB  - The objective of the present study was to evaluate the effects of different
      concentrations of T-2 toxin in feed on performance, lipid peroxidation, and
      genotoxicity in vivo. For a 17-d period, T-2 toxin was added to the diet of the
      chickens. Fifty 22-d-old male broiler chickens were divided into 5 groups that
      were supplemented with different concentrations of T-2 toxin: control (0.0 mg/kg
      of feed), T 0.5 (0.5 mg/kg of feed), T 1.5 (1.5 mg/kg of feed), T 4.5 (4.5 mg/kg
      of feed), and T 13.5 (13.5 mg/kg of feed). Deoxyribonucleic acid fragmentation in
      spleen leukocytes, malondialdehyde in plasma and liver, total plasma
      antioxidative status, glutathione peroxidase activity, and total serum Ig (IgA
      and IgG) were measured. Feed consumption and BW gain decreased when the
      concentration of T-2 toxin was 4.5 and 13.5 mg/kg of feed. Compared with the
      control group, the rate of DNA damage increased significantly in the group fed
      13.5 mg of T-2 toxin/kg of feed. In contrast to DNA fragmentation, indicators of
      oxidative stress did not show differences between groups fed T-2 toxin and the
      control. More serum IgA was detected in the group T 13.5 compared with the
      control, whereas there were no differences in serum IgG levels. The results of
      the present study indicate that impaired performance, DNA fragmentation in spleen
      leukocytes, and elevated serum IgA levels induced by T-2 toxin are dose
      dependent. Based on our results, we could not confirm the hypothesis that
      oxidative stress is among the mechanisms by which T-2 toxin induces DNA
      fragmentation.

PMID- 17495087
TI  - The effects of several oligosaccharides on true amino acid digestibility and true
      metabolizable energy in cecectomized and conventional roosters.
AB  - Prebiotics, such as indigestible oligosaccharides, are considered to be possible
      dietary alternatives to antibiotic growth promoters in poultry. The effects of
      indigestible oligosaccharides on nutrient digestibility in poultry are largely
      unknown. Therefore, an experiment was conducted to evaluate the effects of
      several oligosaccharides on amino acid digestibility and TMEn in roosters. The
      dietary treatments consisted of a corn-isolated soy protein control diet or that
      diet supplemented with 4 or 8 g/kg of inulin, oligofructose,
      mannanoligosaccharide (MOS), short-chain fructooligosaccharide, or
      transgalactooligosaccharide (TOS). Each of the 11 diets was tube-fed (30 g) to 4
      cecectomized and 4 intact Single Comb White Leghorn roosters that had been fasted
      for 24 h. Excreta were then collected for the following 48 h, freeze-dried, and
      analyzed for amino acid content. The true digestibility of lysine and valine was
      increased (P<0.05) in cecectomized roosters fed 8 g/kg of MOS or TOS when
      compared with roosters fed the control diet. In addition, methionine
      digestibility was improved (P<0.05) in cecectomized roosters fed 4 g/kg of MOS or
      short-chain fructooligosaccharide and by 8 g/kg of oligofructose or TOS. The true
      digestibility of isoleucine was increased (P<0.05) in cecectomized roosters fed 8
      g/kg of MOS or 4 or 8 g/kg of TOS. The magnitude of the increases in amino acid
      digestibility coefficients for cecectomized roosters ranged from 3 to 9
      percentage units. Feeding either 4 or 8 g/kg of inulin to intact roosters
      decreased (P<0.05) the true digestibility of methionine. The oligosaccharides
      generally had no significant effect on TMEn. The results of this study indicated
      that the indigestible oligosaccharides had no significant effect on the
      digestibility of most amino acids in a corn-isolated soy protein diet. The
      digestibility of a few amino acids, however, was increased by some
      oligosaccharides in cecectomized roosters but not in intact roosters.

PMID- 17495088
TI  - Expression of cell-cycle-regulating genes in the development of atherosclerosis
      in Japanese quail (Coturnix japonica).
AB  - The levels of mRNA expression in regulatory genes that are involved in the
      pathological changes of aortic atherosclerotic and fibroblastic intimal
      thickening was investigated in Japanese quail. The quail were divided into a
      control diet group and an atherogenic diet group. The quail were euthanized at 2,
      4, 8, and 12 wk after consuming either a control diet or an atherogenic diet.
      Thereafter, both histological and immunohistochemical studies and mRNA expression
      analysis of the cell-cycle-regulating genes in aortic atherosclerotic lesions
      were performed on selected ascending aortas and their large branches. In the
      atherogenic diet group, aortic lipid-containing intimal and atheromatous lesions
      were seen mainly at 8 and 12 wk, respectively. Semiquantitative reverse
      transcription PCR was used to analyze the alterations of mRNA expression on the
      development of atherosclerotic lesions. Messenger RNA expression of the c-fos and
      c-src genes showed peak levels at 8 wk in the atherogenic diet group. However, no
      significant alteration of c-jun mRNA expression was noted during the entire
      experimental period. According to the progression of aortic atherosclerotic
      lesions, c-myc mRNA expression in the atherogenic diet group increased
      chronologically, and the highest level was observed at 12 wk. Alterations in mRNA
      expression of proliferating cell nuclear antigen and the p27 gene were similar to
      that of c-myc. The levels of c-myc, proliferating cell nuclear antigen, and p27
      mRNA expression was significantly correlated with the degree of aortic
      atherosclerotic lesion development at 12 wk in our experiment.

PMID- 17495089
TI  - Ontogenesis of the expression of prolactin receptor messenger ribonucleic acid
      during late embryogenesis in turkeys and chickens.
AB  - Changes in circulating levels of prolactin (PRL) and tissue content of PRL
      receptor (PRLR) messenger RNA (mRNA) in the liver, pancreas, kidney, and gonads
      (testis/ovary) were measured in turkey and chicken embryos from embryonic day
      (ED) 21 or ED15, respectively, to 1 d after hatch by real-time PCR. There were no
      differences between the sexes in chickens or turkeys. Both species had very
      similar patterns of PRL release and expression of PRLR mRNA, and no major
      differences were observed between turkey or chicken embryos. Plasma levels of PRL
      increased from low levels during the last week of embryonic development and were
      at significantly higher levels (about 4-fold) by 1 d after hatch. Similarly, in
      all tissues the content of PRLR mRNA was minimal at the outset and increased to
      reach maxima about the time of hatch. In both species, the highest levels of
      transcript were observed in the kidney followed by the gonad, liver, and
      pancreas. The tissue content of PRLR was correlated (0.6 to 0.8 dependent on the
      tissue) to circulating levels of PRL, which suggested that PRL may be associated
      with an increase in its receptor number around the time of hatch. Because levels
      of PRL and tissue content of PRLR mRNA increased around the time of hatch, this
      suggests that these tissues may be targets for PRL and may be involved in the
      physiologic changes occurring in embryos around the time of hatching.

PMID- 17495090
TI  - Effect of dietary supplementation with conjugated linoleic acid, with oleic,
      linoleic, or linolenic acid, on egg quality characteristics and fat accumulation
      in the egg yolk.
AB  - The effects of conjugated linoleic acid (CLA) with other fatty acids on the fatty
      acid composition of egg yolk and on egg quality characteristics were studied in 5
      groups: 1) CLA 0% (control), 2) CLA 2%, 3) CLA 2%+oleic acid (OA) 2% (CLA+OA), 4)
      CLA 2%+linoleic acid (LA) 2% (CLA+LA), and 5) CLA 2%+alpha-linolenic acid (LNA)
      2% (CLA+LNA). Some parameters of egg quality such as shell thickness, shell
      strength, yolk color, yolk index, egg diameter, and Haugh units were aggravated
      when CLA was fed alone, but the quality was improved when CLA was combined with
      some other fatty acids. The egg production rate, which was decreased by feeding
      CLA alone, was improved by co-supplementation with LA or OA. An increase in CLA
      content was observed in all the dietary groups fed CLA for 2 wk. Feeding hens
      with CLA+LNA led to a linear increase in CLA content in the egg yolk after the
      fourth week of the feeding trial. Egg yolks from hens given CLA had considerably
      higher amounts of saturated fatty acids and lower amounts of monounsaturated
      fatty acids than egg yolks from the control group. The pattern of change in CLA
      concentration during the feeding trial was similar to the level of C18:0, which
      was inversely correlated with the level of C18:1. The unsaturated fatty acid co
      supplementation strategy applied in this study offers insight into the mechanism
      of CLA accumulation in the egg yolk without apparent adverse effects on egg
      quality and egg production.

PMID- 17495091
TI  - Effects of clofibrate treatment in laying hens.
AB  - Expression of peroxisome proliferator-activated receptor-alpha (PPARalpha) has
      been shown in liver of chicks, but effects of its activation have not yet been
      investigated. In this study, laying hens were treated with clofibrate, a
      synthetic PPARalpha agonist, to investigate the effects of PPARalpha activation
      on liver lipid metabolism. Hens receiving a diet containing 5 g of clofibrate/kg
      had a lower food intake and higher liver mRNA concentrations of typical PPARalpha
      target genes (carnitine palmitoyltransferase 1A, acyl-coenzyme A oxidase,
      bifunctional enzyme, lipoprotein lipase) involved in hepatic mitochondrial and
      peroxisomal beta-oxidation and plasma triglyceride clearance than control hens
      that received the same diet without clofibrate (P<0.05). Hens treated with
      clofibrate also had lower mRNA concentrations of fatty acid synthase, 3-hydroxy-3
      methylglutaryl-coenzyme A reductase, and low-density lipoprotein receptor,
      proteins involved in fatty acid biosynthesis and cholesterol biosynthesis and
      uptake, than hens fed the control diet (P<0.05). These changes in clofibrate
      treated hens were accompanied by reduced liver triglyceride concentrations,
      strongly diminished very low density triglyceride and cholesterol concentrations
      (P<0.05), a disturbed maturation of egg follicles, a complete stop of egg
      production, and a markedly reduced plasma 17-beta-estradiol concentration
      (P<0.05). In conclusion, it is shown that clofibrate has complex effects on
      hepatic lipid metabolism in laying hens that mimic PPARalpha activation in
      mammals, affect maturation of egg follicles, and lead to a stop of egg
      production. Because clofibrate treatment strongly reduced food intake in the
      hens, some of these effects (i.e., egg production) may have been due to a low
      energy and nutrient intake.

PMID- 17495092
TI  - Production of a polyclonal anti-myostatin antibody and the effects of in ovo
      administration of the antibody on posthatch broiler growth and muscle mass.
AB  - In this study, we produced a polyclonal antibody against unprocessed chicken
      myostatin and examined the effect of in ovo administration of the antibody on
      posthatch chicken growth and muscle mass. A PCR-amplified unprocessed chicken
      myostatin cDNA was cloned into an Escherichia coli expression vector, and
      myostatin proteins were expressed. Recombinant myostatin purified by electro
      elution of the SDS-PAGE fractionated myostatin band was used as an immunogen to
      produce rabbit polyclonal antimyostatin antibody (pAb-AVM46). In Western blot
      analysis, the pAb-AVM46 showed high affinity to the myostatin propeptide, but
      little affinity to the mature myostatin. Two experiments examined the effect of
      in ovo administration of the pAb-AVM46 on posthatch chicken growth and skeletal
      muscle mass. In experiment 1, broilers from eggs injected once with 35 microg of
      the antibody into the yolk on d 3 of incubation had significantly lower combined
      thigh and leg weight at 4 wk posthatch than the controls that received no
      injection, or the broilers from eggs received the same dose of antibody into the
      albumen. In experiment 2, 2 different doses of the antibody (9 or 70 microg) were
      injected into the yolk, and the effects on body and muscle weight were examined
      at 5 wk posthatch. Birds from eggs injected with 70 microg of the antibody had
      significantly lighter (11.6%) combined thigh and leg weight than the control
      birds. The percentage of the combined thigh and leg weight to BW of the 70-microg
      group was also significantly lower than that of the control group (20.95 vs.
      23.08%). The results of this study indicate that unprocessed full-length
      myostatin as an immunogen produced antibody populations having affinity mostly to
      the propeptide with little to the mature form. The decreased muscle weight
      observed in broilers injected with the antibody in the yolk indicates that
      myostatin activity was probably elevated by the binding of the antibody to the
      propeptide, and provides evidence that myostatin propeptide inhibits the
      biological activity of myostatin in broilers.

PMID- 17495093
TI  - The differential expression of hepatic genes between prelaying and laying geese.
AB  - Suppression subtractive hybridization was used to detect differential expression
      of genes in the livers of laying and prelaying geese. Liver tissues from
      prelaying and laying geese were dissected for mRNA extraction. The cDNA, reverse
      transcribed from liver mRNA of prelaying geese, was subtracted from the cDNA
      generated from the laying geese (forward subtraction). Five hundred seventy-six
      clones with possible differentially expressed gene fragments were observed by
      forward subtraction hybridization. After differential screening using the reverse
      and forward subtraction cDNA, 164 clones were subjected to gene sequence
      determination and further analysis. Using Northern analysis, 5 known and 8
      unknown genes were shown to be highly expressed in the livers of laying geese
      compared with prelaying geese. Vitellogenin I, apoVLDL-II, ethanolamine kinase, G
      protein gamma-5 subunit, and leucyl-tRNA synthase were highly expressed in the
      livers of laying geese compared with that from the prelaying geese (P<0.05). The
      expression of these known genes suggests that their function in the liver of
      laying geese is primarily involved in lipid and lipoprotein metabolism. Several
      of these differentially expressed genes were found to be responsive to estrogen
      stimulation, confirming the involvement of these genes in the egg-laying function
      of the goose.

PMID- 17495094
TI  - Cloacal gland growth differences in high and low plasma corticosterone stress
      response line male quail reared under short daylengths.
AB  - Mail quail selected (generation 32) for reduced [low stress (LS)] or exaggerated
      [high stress (HS)] plasma corticosterone stress response to brief mechanical
      restraint (5 min of immobilization) were studied for differences in the growth of
      their cloacal glands when reared essentially lifelong on short day lengths of
      8L:16D. Post-brooding, at 4 wk of age, 96 quail (48 LS+48 HS) were housed in
      cages (1 LS and 1 HS male/cage), and the short day light treatment was
      instigated. Using a digital caliper, cloacal gland (CG) size measurements (length
      and width, mm) were made biweekly beginning at 42 d of age and ending at 196 d of
      age (28 wk old). The CG volume (CVOL) was calculated from these measurements
      using a literature-proposed formula. The CVOL in both lines increased similarly
      with increasing age from 6 to 12 wk of age. However, beginning at 14 wk of age
      and thereafter, LS males showed greater (P<0.05) CVOL than HS ones. No further
      increases in CVOL were observed in either line at 24 wk of age beyond that seen
      at 22 wk. This study demonstrated that although both lines show CG development
      under short days, eventually CG growth becomes comparatively stymied in the HS
      males. Furthermore, the maintenance of similarly lower CVOL in HS than LS males,
      CVOL that showed no further increase from 22 to 24 wk of age, suggests that
      holding these quail lifelong on short days results in, comparatively, yet another
      permanent negative reproductive consequence in quail selected for exaggerated
      plasma corticosterone stress responsiveness.

PMID- 17495095
TI  - Aerobic and anaerobic microbiology of the immersion chilling procedure during
      poultry processing.
AB  - The development of treatments to reduce bacterial numbers on poultry carcasses is
      important for the overall hygienic quality of birds. The important washing effect
      of the immersion chilling procedure is discussed. Systematic monitoring of fecal
      bacterial indicators as well as some classic pathogens was performed at selected
      critical points in a water chiller ecosystem. Clostridium perfringens, fecal
      coliforms, Enterococcus sp., and Streptococcus sp. were found in all water
      chiller samples. The temperature of the chiller ecosystem varied according to
      location: Escherichia coli and Salmonella sp. were found at 16 degrees C,
      compared with the 4 degrees C location, where these species were found in lower
      numbers. Moreover, the psychrotrophic bacterium Pseudomonas was found only at
      this last location. The temperature of the water during the immersion chilling
      procedure was unfavorable for the growth of Campylobacter sp., whose presence was
      always strictly associated with a pH close to 6. Spore forms of C. perfringens
      were persistent in all locations and seemed to be a reliable indicator of
      contamination of the water chiller ecosystem.

PMID- 17495096
TI  - Campylobacter in Finnish organic laying hens in autumn 2003 and spring 2004.
AB  - A total of 642 fecal samples and 360 table eggs from Finnish organic laying hens
      were collected in autumn 2003 (19 farms) and spring 2004 (17 farms) and studied
      for the presence of Campylobacter. In autumn, 84% of the farms were positive for
      Campylobacter and in spring, 76%. The percentage of positive samples within a
      flock varied between 5 and 100%. In addition, Campylobacter was isolated in a
      single eggshell sample. Campylobacter jejuni was the species isolated most often,
      although Campylobacter coli was detected on 3 farms in autumn and on 4 farms in
      spring. KpnI pulsed-field gel electrophoresis genotyping revealed a high level of
      diversity among the isolates; 47 different patterns were detected among a total
      of 162 isolates studied. On most of the farms, the genotypes identified in autumn
      and spring were different, also indicating temporal diversity among colonizing
      isolates. However, some predominant persistent genotypes were also detected among
      the isolates. These results suggest that the pool of colonizing isolates may
      include both variants with capability for persistent intestinal colonization in
      hens as well as variants with short-term colonization characteristics. In
      antimicrobial susceptibility testing, the majority of isolates were susceptible
      to ciprofloxacin, tetracycline, ampicillin, and nalidixic acid. On 2 farms,
      isolates resistant to nalidixic acid and to ciprofloxacin were detected. In
      conclusion, Finnish organic laying hens are often colonized by a diversity of
      Campylobacter pulsed-field gel electrophoresis genotypes.

PMID- 17495097
TI  - Subtherapeutic tylosin phosphate in broiler feed affects Campylobacter on
      carcasses during processing.
AB  - Tylosin phosphate is an antimicrobial drug approved for use in broiler feed at
      subtherapeutic levels for growth promotion. Erythromycin is often the drug of
      choice for treating humans with campylobacteriosis. Both tylosin and erythromycin
      are classified as macrolide drugs and cross-resistance between these
      antimicrobials occurs. Commercial broiler chicks were placed in isolation grow
      out chambers and colonized with Campylobacter jejuni. From 14 d of age through
      grow-out, broilers were fed ad libitim a diet that included 22 ppm of tylosin
      phosphate (20 g/ton). Control broilers received the same diet without tylosin
      phosphate. At 42 d of age, broilers were processed in a pilot plant with
      equipment that closely modeled commercial conditions. Carcass rinses were
      collected after feather removal, after inside and outside washing, and after
      immersion chilling. Campylobacter numbers recovered from carcasses after feather
      removal did not differ according to feed type (3.53 log cfu/mL of rinse for
      control carcasses, and 3.60 log cfu/mL of rinse for those fed medicated feed).
      Likewise, medicated feed did not affect Campylobacter numbers on carcasses after
      inside-outside washing (3.11 and 3.07 log cfu/mL of rinse). However, carcasses of
      broilers fed tylosin phosphate had lower numbers of Campylobacter after chilling
      (1.45 log cfu/mL of rinse) than control carcasses (2.31 log cfu/mL of rinse). No
      Campylobacter isolated from control carcasses were resistant to erythromycin; all
      Campylobacter recovered from carcasses fed tylosin phosphate were resistant to
      erythromycin. Application of tylosin phosphate in feed results in lower numbers
      of Campylobacter on chilled carcasses; however, the Campylobacter that do remain
      are resistant to erythromycin.

PMID- 17495098
TI  - Performance and histological responses of internal organs of broiler chickens fed
      raw, dehulled, and aqueous and dry-heated kidney bean meals.
AB  - The objective of the present study was to investigate the effect of raw and
      differently processed [aqueous heating, dehulled, and dry heating (toasted)]
      kidney bean meals on the performance, weights, and histology of internal organs
      of broiler chicken. The feeding trial lasted for 56 d. Two hundred twenty-five 1
      d-old broiler chicks (Anak strain) were used for the study. There were 5
      treatment groups of 3 replicates with 15 birds per replicate. Raw and processed
      kidney bean meals were used to replace 50% protein supplied by soybean in the
      control diet. Data collected were used to evaluate feed intake, weight gain, and
      efficiency of feed utilization. The weights of liver, pancreas, kidney, heart,
      and lungs were also recorded and tissue samples of each collected for
      histological examination. Average daily food intake, average daily gain, and
      efficiency of feed utilization were influenced by the dietary treatments. Average
      daily food intake and average daily gain in birds fed the control diet and heat
      treated kidney bean meals were similar and significantly (P<0.05) higher than
      those fed raw or dehulled meals. Feed conversion ratio was significantly (P<0.05)
      higher in birds fed raw or dehulled meals compared with those fed the control
      diet. The relative weight of the pancreas was significantly (P<0.05) increased as
      a result of acinar hypertrophy. The kidney had severe congestion of glomeruli and
      distention of the capillary vessels with numerous thrombi in birds fed raw and
      dehulled kidney bean meals. The weight of the liver was significantly (P<0.05)
      reduced in birds fed raw and dehulled meals, and the liver was characterized by
      marked coagulative necrosis and degeneration of the hepatocytes. The structural
      alterations were attributed to intake of trypsin inhibitors and haemagglutinins
      in the processed seeds. In conclusion, aqueous heated kidney bean meal can be
      used to replace 50% protein supplied by soybean meal in broiler starter and
      finisher diets without any adverse effect on the performance and the internal
      organs.

PMID- 17495099
TI  - Effect of external or internal fecal contamination on numbers of bacteria on
      prechilled broiler carcasses.
AB  - During processing, fecal material may contact broiler carcasses externally or
      internally. A study was conducted to determine the effect of external vs.
      internal fecal contamination on numbers of bacteria on broiler carcasses. In each
      of 3 trials, 12 carcasses just prior to evisceration were obtained from a
      commercial processing plant, placed on a shackle line, and eviscerated with
      commercial equipment in a pilot scale processing plant. Also, approximately 20
      intestinal tracts were collected from the processing plant; then cecal contents
      were collected and pooled. One gram of cecal content was placed on the exterior
      breast skin (external), inside the carcass cavity (internal), or not applied
      (control). All carcasses were held 10 min, then placed on the shackle line and
      passed through a commercial inside-outside bird washer set at 552 kPa, 5 s dwell
      time, using approximately 189 L per min of tap water at ambient temperature.
      After a 1-min drip, whole carcass rinses were conducted on each carcass, and
      coliforms, Escherichia coli, and Campylobacter counts were determined and
      reported as log cfu/mL of rinse. External carcass contamination resulted in
      significantly higher (P<0.05) coliform, E. coli, and Campylobacter numbers than
      internal contamination (5.0 vs. 4.5, 4.9 vs. 4.2, and 3.6 vs. 2.6, respectively).
      Control carcass counts were significantly lower than external or internal carcass
      contamination counts for coliforms (3.7), E. coli (3.6), and Campylobacter (2.2).
      External contamination resulted in higher numbers of bacteria after carcass
      washing, but carcasses with internal contamination still have higher numbers of
      bacteria after washing than carcasses without applied contamination.

PMID- 17495100
TI  - Role of interleukin-6 in the pathogenesis of an avian model of Staphylococcus
      aureus arthritis.
AB  - To evaluate the role of interleukin-6 (IL-6) in arthritis induced by
      Staphylococcus aureus, a chicken model was developed for study. A total of 120
      healthy broilers (8 wk old) were randomly divided into 4 groups. Two groups were
      injected with 0.35 mL of Staph. aureus (7.1x10(9) cfu/mL) into the right hock
      joints and the other 2 were injected with 0.35 mL of sterile saline into the same
      joints. One group of each of the 2 treatment groups was fed levofloxacin at a
      dose of 5 mg/kg of BW on the third day postinoculation for 4 successive days.
      Chicken blood samples were obtained on d 0, 1, 4, 7, 14, 21, 28, and 35
      postinoculation. Chicken IL-6 (chIL-6) activities and concentrations in serum
      were quantified by B9 bioassay and human IL-6 ELISA, respectively. The results
      showed that chIL-6 activities and concentrations were reduced (P<0.05) in the
      serum of infected broilers treated with levofloxacin compared with birds injected
      only with Staph. aureus. Levofloxacin treatment had no effect on IL-6 activities
      and concentrations in uninfected broilers. There was a strong correlation
      (r=0.91) between serum chIL-6 activities by the B9 bioassay and serum IL-6
      concentrations determined by the human IL-6 ELISA. We concluded that chIL-6 is
      involved in the progression of chicken arthritis induced by Staph. aureus, and
      that it contributes to disease incidence and mortality.

PMID- 17495101
TI  - Realistic views concerning poultry welfare.
AB  - The animal welfare (rights) issue we face today is not one that will be resolved
      through research or factual knowledge. It is an emotional issue that resides on
      philosophical beliefs that are often associated with the religion of an
      individual or his or her lack thereof. Individuals who oppose the use of animals
      for research, food, companionship, etc., based on personal feelings or
      philosophies, may never change their minds based on scientific facts. However,
      the opportunity we have is the minds of those people who have not yet made up
      their mind. We can instill in them a respect for life and a clear understanding
      that it is okay to utilize animals for companionship and for food production
      provided the animals are maintained under acceptable and reasonable conditions
      and that they are cared for in a humane manner. This issue will continue to be a
      tough battle, because, from past experience, animal rightists will sometimes
      stage animal abuse to prove their viewpoint. We must also realize that due to the
      nature of humans, not everyone who is responsible for animals, in both research
      and production settings, will properly care for them. Animal mistreatment or
      abuse is a major black eye for everyone, and it is always caused by individuals
      who do not handle animals in a humane and proper manner. However, we have to
      admit that humanity has reverted to some very deplorable states in history.

PMID- 17495102
TI  - Animal care guidelines and future directions.
AB  - Two notions broadly accepted in developed western societies have made animal care
      guidelines inevitable. These are that domestic animals are sentient and that
      humans are responsible to ensure the proper care of domestic animals. Despite
      these common views, people have differing moral understandings of the human
      animal relationship, and there are sharp divisions over how these views should be
      applied to domestic animal care. Animal care guidelines have been developed by
      different nations at several organizational levels to represent a compromise that
      is acceptable to most people. These organizational levels include individual
      poultry companies, national poultry associations, individual customers of the
      poultry industry, national associations of customer companies, national
      governments, and international organizations. Animal care guideline development
      has typically included input from producers and scientists and, depending on the
      sponsoring organization, animal advocates and government representatives as well.
      Animal advocacy groups have also sought to influence domestic animal care by
      campaigning against animal production practices or by offering their preferred
      guidelines for producers to adopt in the hope that the endorsement of the welfare
      group would add value to the product. Originally, animal care guidelines were
      only recommended, with little or no requirement for compliance. In recent years,
      the need for retail companies to assure certain welfare standards has led to
      animal welfare auditing of production facilities. Animal care guidelines
      primarily have sought to establish standards for handling and husbandry in
      existing production systems. Future guidelines may put increasing emphasis on
      adoption of alternative management practices or housing systems. International
      animal care guidelines are being developed on 2 levels (i.e., among national
      governments to create a common standard for trade in animal products and within
      international retail companies to create company-wide animal care standards).
      These initiatives should tend to unify farm animal care standards worldwide but
      perhaps at a level some nations might consider lower than preferable.

PMID- 17495103
TI  - Molting layers--alternative methods and their effectiveness.
AB  - The molting of commercial layers has been under increased scrutiny by animal
      rights groups, who have said that this practice is highly stressful and one which
      negatively affects the welfare of the hen due to the initial period of fasting
      that has been used to stop egg production. In recent years, there has been a
      recognized need to develop practical alternatives to molting layers other than
      the use of fasting. Thus, the University of Illinois, University of Nebraska,
      North Carolina State University, and the University of California have all
      researched this area. In all of these studies, the methods involved comparing a
      normal fasting method (i.e., 5 to 13 d), to feeding low-energy and protein diets
      using ingredients such as wheat middlings, soybean hulls, and corn or diets with
      graded levels of added salt and without salt (University of Nebraska, University
      of California). The molt period (28 d) included full-feeding of these diets. In
      these studies, postmolt production performance for the nonfeed withdrawal
      techniques was comparable to the fasting method. Several researchers have also
      evaluated the behavioral repertoire of laying hens, which includes feeding,
      drinking, comfort, social, reproductive, and anti-predator behaviors. In
      addition, related behaviors such as aggression, escape-avoidance, and submission
      have been of particular interest as potential indicators of welfare during
      molting. In these studies, genetic selection, strain, density, or molt program do
      not appear to adversely influence the behavioral patterns during the molt. The
      behavior patterns displayed during a molt program appear consistent with the
      response to physiological changes that layers experience and do not appear to
      compromise the welfare status of the hens. Appetitive behaviors were not affected
      by strain but were affected by production phase and molting. Strain or production
      phase did not influence the frequency of aggressive and submissive acts. Thus,
      the use of alternative nonfeed withdrawal molting methods provide comparable
      laying hen well-being and may enhance the transition from a productive to a
      resting state.

PMID- 17495104
TI  - Density allowances for broilers: where to set the limits?
AB  - Stocking density has critical implications for the broiler industry because
      higher returns can be obtained as the number of birds per unit space increases.
      Assigned densities have been primarily driven by cost-benefit analysis, but
      economic profit may come at the cost of reduced bird performance, health, and
      welfare if densities are excessive. These negative consequences are the primary
      reason for the increasing demands for guidelines that limit density allowances,
      even through legislation. Current recommended densities are rather variable, and
      therefore it is critical if guidelines are to be established that they be based
      on sound science. Published research consistently indicates that the health and
      welfare of broilers is compromised if space allowances drop below 0.0625 to 0.07
      m2/bird (equivalent to about 34 to 38 kg/m2 depending on final BW). Negative
      consequences include reduced final BW, feed intake and food conversion, and
      greater incidence of foot-pad dermatitis, scratches, bruising, poorer feathering,
      and condemnations. A few studies have also found higher mortalities, tibial
      dischondroplasia, and some evidence of physiological stress. At the behavioral
      level, most studies indicate a reduction in space use and movement and higher
      frequencies of disturbances, which has been linked with a higher frequency of
      scratches and decline in carcass quality. Other main behavioral categories remain
      largely unchanged. However, results overwhelmingly suggest that while stocking
      density has major consequences for the health and welfare of broilers, the
      quality of the environment, which has been largely underestimated, is far more
      relevant. Advances in broiler welfare will be difficult to achieve unless some
      criteria for environmental quality are also established. The implications of this
      are that the welfare of broilers can be ensured at a range of (reasonable)
      densities, as long as the requirements for environmental quality are fulfilled.
      It is also essential for industry to realize that returns per unit of space in
      broiler production do tend to plateau if density is excessive, a result of the
      reduction in bird performance. In this paper I suggest a model that may be used
      to maximize productivity, health, and welfare.

PMID- 17495105
TI  - Neurobiological basis of sensory perception: welfare implications of beak
      trimming.
AB  - The practice of beak trimming in the poultry industry occurs to prevent excessive
      body pecking, cannibalism, and to avoid feed wastage. To assess the welfare
      implications of the procedure, an emphasis of this paper has been placed on the
      anatomical structures that comprise the beak and mouth parts and a representation
      of the structures removed following beak trimming. Five animal welfare concerns
      regarding the procedure have been addressed, including the following: loss of
      normal beak function, short-term pain and temporary debilitation, tongue and
      nostril damage, neuromas and scar tissue, and long-term and phantom limb pain.
      Because all of the concerns involve the nervous system, the current knowledge of
      the avian somatosensory system was summarized. The critical components include
      touch, pain, and thermal receptors in the buccal cavity and bill, the trigeminal
      system, and neural projections mapped to the pallium (cortical-like tissue in the
      avian forebrain). At the present time, a need remains to continue the practice of
      beak trimming in the poultry industry to prevent head, feather, and vent pecking
      in some lines of birds. The procedure, however, should involve conservative
      trimming and be limited to young birds. Importantly, data show that removing 50%
      or less of the beak of chicks can prevent the formation of neuromas and allow
      regeneration of keratinized tissue to prevent deformed beaks and therefore
      positively affect the quality of life of birds during their lifetime.

PMID- 17495107
TI  - Human amniotic epithelial cells as novel feeder layers for promoting ex vivo
      expansion of limbal epithelial progenitor cells.
AB  - Human amniotic epithelial cells (HAECs) are a unique embryonic cell source that
      potentially can be used as feeder layers for expanding different types of stem
      cells. In vivo, HAECs uniformly expressed pan-cytokeratins (pan-CK) and
      heterogeneously expressed vimentin (Vim). The two phenotypes expressing either
      pan-CK(+)/Vim(+) or pan-CK(+)/Vim(-) were maintained in serum-free media with
      high calcium. In contrast, all HAECs became pan-CK(+)/Vim(+) in serum-containing
      media, which also promoted HAEC proliferation for at least eight passages,
      especially supplemented with epidermal growth factor and insulin. Mitomycin C
      arrested HAEC feeder layers were more effective in promoting clonal growth of
      human limbal epithelial progenitors than conventional 3T3 murine feeder layers.
      Cells in HAEC-supported clones were uniformly smaller, sustained more
      proliferation, and expressed less CK12 and connexin 43 but higher levels of stem
      cell-associated markers such as p63, Musashi-1, and ATP-binding cassette
      subfamily G2 than those of 3T3-supported clones. Subculturing of clonally
      expanded limbal progenitors from HAEC feeder layers, but not from 3T3 feeder
      layers, gave rise to uniformly p63-positive epithelial progenitor cells as well
      as nestin-positive neuronal-like progenitors. Collectively, these results
      indicated that HAECs can be used as a human feeder layer equivalent for more
      effective ex vivo expansion of adult epithelial stem cells from the human limbus.
      Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 17495108
TI  - Extensive studies on perfusion method plus intra-bone marrow-bone marrow
      transplantation using cynomolgus monkeys.
AB  - The collection of bone marrow cells (BMCs) using a perfusion method has been
      advantageous not only because of the low contamination of BMCs with T cells from
      the peripheral blood but also the enrichment of stromal cells, which support
      hemopoiesis. Before the application of this new method to humans, its safety
      needed to be confirmed using cynomolgus monkeys. We therefore performed the
      perfusion method on more than 100 cynomolgus monkeys using the long bones (such
      as the humerus and femur) and also the iliac bones (for human application); in
      the more than 150 trials to date, there have been no accidental deaths.
      Furthermore, the technical safety of a new method for the intra-bone marrow (IBM)
      injection of BMCs (termed IBM-bone marrow transplantation) has also been
      confirmed using 30 monkeys. Disclosure of potential conflicts of interest is
      found at the end of this article.

PMID- 17495109
TI  - Concise review: trends in stem cell proteomics.
AB  - Gene expression analyses of stem cells (SCs) will help to uncover or further
      define signaling pathways and molecular mechanisms involved in the maintenance of
      self-renewal, pluripotency, and/or multipotency. In recent years, proteomic
      approaches have produced a wealth of data identifying proteins and mechanisms
      involved in SC proliferation and differentiation. Although many proteomics
      techniques have been developed and improved in peptide and protein separation, as
      well as mass spectrometry, several important issues, including sample
      heterogeneity, post-translational modifications, protein-protein interaction, and
      high-throughput quantification of hydrophobic and low-abundance proteins, still
      remain to be addressed and require further technical optimization. This review
      summarizes the methodologies used and the information gathered with proteome
      analyses of SCs, and it discusses biological and technical challenges for
      proteomic study of SCs. Disclosure of potential conflicts of interest is found at
      the end of this article.

PMID- 17495110
TI  - Phosphoserine phosphatase is expressed in the neural stem cell niche and
      regulates neural stem and progenitor cell proliferation.
AB  - Phosphoserine phosphatase (PSP) metabolizes the conversion of l-phosphoserine to
      l-serine, classically known as an amino acid necessary for protein and nucleotide
      synthesis and more recently suggested to be involved in cell-to-cell signaling.
      Previously, we identified PSP as being enriched in proliferating neural
      progenitors and highly expressed by embryonic and hematopoietic stem cells,
      suggesting a general role in stem cells. Here we demonstrate that PSP is highly
      expressed in periventricular neural progenitors in the embryonic brain. In the
      adult brain, PSP expression was observed in slowly dividing or quiescent glial
      fibrillary acidic protein (GFAP)-positive cells and CD24-positive ependymal cells
      in the forebrain germinal zone adjacent to the lateral ventricle and within GFAP
      positive cells of the hippocampal subgranular zone, consistent with expression in
      adult neural stem cells. In vitro, PSP overexpression promoted proliferation,
      whereas small interfering RNA-induced knockdown inhibited proliferation of neural
      stem cells derived from embryonic cortex and adult striatal subventricular zone.
      The effects of PSP knockdown were partially rescued by exogenous l-serine. These
      data support a role for PSP in neural stem cell proliferation and suggest that in
      the adult periventricular germinal zones, PSP may regulate signaling between
      neural stem cells and other cells within the stem cell niche. Disclosure of
      potential conflicts of interest is found at the end of this article.

PMID- 17495111
TI  - The myogenic factor Myf5 supports efficient skeletal muscle regeneration by
      enabling transient myoblast amplification.
AB  - The myogenic factor Myf5 defines the onset of myogenesis in mammals during
      development. Mice lacking both Myf5 and MyoD fail to form myoblasts and are
      characterized by a complete absence of skeletal muscle at birth. To investigate
      the function of Myf5 in adult skeletal muscle, we generated Myf5 and mdx compound
      mutants, which are characterized by constant regeneration. Double mutant mice
      show an increase of dystrophic changes in the musculature, although these mice
      were viable and the degree of myopathy was modest. Myf5 mutant muscles show a
      small decrease in the number of muscle satellite cells, which was within the
      range of physiological variations. We also observed a significant delay in the
      regeneration of Myf5 deficient skeletal muscles after injury. Interestingly, Myf5
      deficient skeletal muscles were able to even out this flaw during the course of
      regeneration, generating intact muscles 4 weeks after injury. Although we did not
      detect a striking reduction of MyoD positive activated myoblasts or of Myf5-LacZ
      positive cells in regenerating muscles, a clear decrease in the proliferation
      rate of satellite cell-derived myoblasts was apparent in satellite cell-derived
      cultures. The reduction of the proliferation rate of Myf5 mutant myoblasts was
      also reflected by a delayed transition from proliferation to differentiation,
      resulting in a reduced number of myotube nuclei after 6 and 7 days of culture. We
      reason that Myf5 supports efficient skeletal muscle regeneration by enabling
      transient myoblast amplification. Disclosure of potential conflicts of interest
      is found at the end of this article.

PMID- 17495112
TI  - Finding fluorescent needles in the cardiac haystack: tracking human mesenchymal
      stem cells labeled with quantum dots for quantitative in vivo three-dimensional
      fluorescence analysis.
AB  - Stem cells show promise for repair of damaged cardiac tissue. Little is known
      with certainty, however, about the distribution of these cells once introduced in
      vivo. Previous attempts at tracking delivered stem cells have been hampered by
      the autofluorescence of host tissue and limitations of existing labeling
      techniques. We have developed a novel loading approach to stably label human
      mesenchymal stem cells with quantum dot (QD) nanoparticles. We report the
      optimization and validation of this long-term tracking technique and highlight
      several important biological applications by delivering labeled cells to the
      mammalian heart. The bright QD crystals illuminate exogenous stem cells in
      histologic sections for at least 8 weeks following delivery and permit, for the
      first time, the complete three-dimensional reconstruction of the locations of all
      stem cells following injection into the heart. Disclosure of potential conflicts
      of interest is found at the end of this article.

PMID- 17495113
TI  - Matrix metalloprotease activity is an essential link between mechanical stimulus
      and mesenchymal stem cell behavior.
AB  - Progenitor cells are involved in the regeneration of the musculoskeletal system,
      which is known to be influenced by mechanical boundary conditions. Furthermore,
      matrix metalloproteases (MMPs) and tissue-specific inhibitors of metalloproteases
      (TIMPs) are crucial for matrix remodelling processes that occur during
      regeneration of bone and other tissues. This study has therefore investigated
      whether MMP activity affects mesenchymal stem cell (MSC) behavior and how MMP
      activity is influenced by the mechanical stimulation of these cells. Broad
      spectrum inhibition of MMPs altered the migration, proliferation, and osteogenic
      differentiation of MSCs. Expression analysis detected MMP-2, -3, -10, -11, -13,
      and -14, as well as TIMP-2, in MSCs at the mRNA and protein levels. Mechanical
      stimulation of MSCs led to an upregulation of their extracellular gelatinolytic
      activity, which was consistent with the increased protein levels seen for MMP-2, 
      3, -13, and TIMP-2. However, mRNA expression levels of MMPs/TIMPs showed no
      changes in response to mechanical stimulation, indicating an involvement of post
      transcriptional regulatory processes such as alterations in MMP secretion or
      activation. One potential regulatory molecule might be the furin protease.
      Specific inhibition of MMP-2, -3, and -13 showed MMP-13 to be involved in
      osteogenic differentiation. The results of this study suggest that MSC function
      is controlled by MMP activity, which in turn is regulated by mechanical
      stimulation of cells. Thus, MMP/TIMP balance seems to play an essential role in
      transferring mechanical signals into MSC function. Disclosure of potential
      conflicts of interest is found at the end of this article.

PMID- 17495114
TI  - The significant cardiomyogenic potential of human umbilical cord blood-derived
      mesenchymal stem cells in vitro.
AB  - We tested the cardiomyogenic potential of the human umbilical cord blood-derived
      mesenchymal stem cells (UCBMSCs). Both the number and function of stem cells may
      be depressed in senile patients with severe coronary risk factors. Therefore,
      stem cells obtained from such patients may not function well. For this reason,
      UCBMSCs are potentially a new cell source for stem cell-based therapy, since such
      cells can be obtained from younger populations and are being routinely utilized
      for clinical patients. The human UCBMSCs (5 x 10(3) per cm(2)) were cocultured
      with fetal murine cardiomyocytes ([CM] 1 x 10(5) per cm(2)). On day 5 of
      cocultivation, approximately half of the green fluorescent protein (GFP)-labeled
      UCBMSCs contracted rhythmically and synchronously, suggesting the presence of
      electrical communication between the UCBMSCs. The fractional shortening of the
      contracted UCBMSCs was 6.5% +/- 0.7% (n = 20). The UCBMSC-derived cardiomyocytes
      stained positive for cardiac troponin-I (clear striation +) and connexin 43
      (diffuse dot-like staining at the margin of the cell) by the immunocytochemical
      method. Cardiac troponin-I positive cardiomyocytes accounted for 45% +/- 3% of
      GFP-labeled UCBMSCs. The cardiomyocyte-specific long action potential duration
      (186 +/- 12 milliseconds) was recorded with a glass microelectrode from the GFP
      labeled UCBMSCs. CM were observed in UCBMSCs, which were cocultivated in the same
      dish with mouse cardiomyocytes separated by a collagen membrane. Cell fusion,
      therefore, was not a major cause of CM in the UCBMSCs. Approximately half of the
      human UCBMSCs were successfully transdifferentiated into cardiomyocytes in vitro.
      UCBMSCs can be a promising cellular source for cardiac stem cell-based therapy.
      Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 17495115
TI  - Methacholine responsiveness in mice from 2 to 8 wk of age.
AB  - Many chronic human lung diseases have their origin in early childhood, yet most
      murine models used to study them utilize adult mice. An important component of
      the asthma phenotype is exaggerated airway responses, frequently modelled by
      methacholine (MCh) challenge. The present study was undertaken to characterize
      MCh responses in mice from 2 to 8 wk of age measuring absolute lung volume and
      volume-corrected respiratory mechanics as outcome variables. Female BALB/c mice
      aged 2, 3, 4, 6, and 8 wk were studied during cumulative intravenous MCh
      challenge. Following each MCh dose, absolute lung volume was measured
      plethysmographically at functional residual volume and during a slow inflation to
      20-hPa transrespiratory pressure. Respiratory system impedance was measured
      continuously during the inflation maneuver and partitioned into airway and
      constant-phase parenchymal components by model fitting. Volume-corrected
      (specific) estimates of respiratory mechanics were calculated. Intravenous MCh
      challenge induced a predominantly airway response with no evidence of airway
      closure in any age group. No changes in functional residual volume were seen in
      mice of any age during the MCh challenge. The specific airway resistance MCh dose
      response curves did not show significant differences between the age groups. The
      results from the present study do not show systematic differences in MCh
      responsiveness in mice from 2 to 8 wk of age.

PMID- 17495116
TI  - Prior exercise speeds pulmonary O2 uptake kinetics by increases in both local
      muscle O2 availability and O2 utilization.
AB  - The effect of prior exercise on pulmonary O(2) uptake (Vo(2)(p)), leg blood flow
      (LBF), and muscle deoxygenation at the onset of heavy-intensity alternate-leg
      knee-extension (KE) exercise was examined. Seven subjects [27 (5) yr; mean (SD)]
      performed step transitions (n = 3; 8 min) from passive KE following no warm-up
      (HVY 1) and heavy-intensity (Delta50%, 8 min; HVY 2) KE exercise. Vo(2)(p) was
      measured breath-by-breath; LBF was measured by Doppler ultrasound at the femoral
      artery; and oxy (O(2)Hb)-, deoxy (HHb)-, and total (Hb(tot)) hemoglobin/myoglobin
      of the vastus lateralis muscle were measured continuously by near-infrared
      spectroscopy (NIRS; Hamamatsu NIRO-300). Phase 2 Vo(2)(p), LBF, and HHb data were
      fit with a monoexponential model. The time delay (TD) from exercise onset to an
      increase in HHb was also determined and an HHb effective time constant (HHb - MRT
      = TD + tau) was calculated. Prior heavy-intensity exercise resulted in a speeding
      (P < 0.05) of phase 2 Vo(2)(p) kinetics [HVY 1: 42 s (6); HVY 2: 37 s (8)], with
      no change in the phase 2 amplitude [HVY 1: 1.43 l/min (0.21); HVY 2: 1.48 l/min
      (0.21)] or amplitude of the Vo(2)(p) slow component [HVY 1: 0.18 l/min (0.08);
      HVY 2: 0.18 l/min (0.09)]. O(2)Hb and Hb(tot) were elevated throughout the on
      transient following prior heavy-intensity exercise. The tauLBF [HVY 1: 39 s (7);
      HVY 2: 47 s (21); P = 0.48] and HHb-MRT [HVY 1: 23 s (4); HVY 2: 21 s (7); P =
      0.63] were unaffected by prior exercise. However, the increase in HHb [HVY 1: 21
      microM (10); HVY 2: 25 microM (10); P < 0.001] and the HHb-to-Vo(2)(p) ratio
      [(HHb/Vo(2)(p)) HVY 1: 14 microM x l(-1) x min(-1) (6); HVY 2: 17 microM x l(-1)
      x min(-1) (5); P < 0.05] were greater following prior heavy-intensity exercise.
      These results suggest that the speeding of phase 2 tauVo(2)(p) was the result of
      both elevated local O(2) availability and greater O(2) extraction evidenced by
      the greater HHb amplitude and HHb/Vo(2)(p) ratio following prior heavy-intensity
      exercise.

PMID- 17495117
TI  - Dangerous exercise: lessons learned from dysregulated inflammatory responses to
      physical activity.
AB  - Exercise elicits an immunological "danger" type of stress and inflammatory
      response that, on occasion, becomes dysregulated and detrimental to health.
      Examples include anaphylaxis, exercise-induced asthma, overuse syndromes, and
      exacerbation of intercurrent illnesses. In dangerous exercise, the normal balance
      between pro- and anti-inflammatory responses is upset. A possible
      pathophysiological mechanism is characterized by the concept of exercise
      modulation of previously activated leukocytes. In this model, circulating
      leukocytes are rendered more responsive than normal to the immune stimulus of
      exercise. For example, in the case of exercise anaphylaxis, food-sensitized
      immune cells may be relatively innocuous until they are redistributed during
      exercise from gut-associated circulatory depots, like the spleen, into the
      central circulation. In the case of asthma, the prior activation of leukocytes
      may be the result of genetic or environmental factors. In the case of overuse
      syndromes, the normally short-lived neutrophil may, because of acidosis and
      hypoxia, inhibit apoptosis and play a role in prolongation of inflammation rather
      than healing. Dangerous exercise demonstrates that the stress/inflammatory
      response caused by physical activity is robust and sufficiently powerful,
      perhaps, to alter subsequent responses. These longer term effects may occur
      through as yet unexplored mechanisms of immune "tolerance" and/or by a training
      associated reduction in the innate immune response to brief exercise. A better
      understanding of sometimes failed homeostatic physiological systems can lead to
      new insights with significant implication for clinical translation.

PMID- 17495118
TI  - Mechanism of partial adaptation in airway smooth muscle after a step change in
      length.
AB  - The phenomenon of length adaptation in airway smooth muscle (ASM) is well
      documented; however, the underlying mechanism is less clear. Evidence to date
      suggests that the adaptation involves reassembly of contractile filaments,
      leading to reconfiguration of the actin filament lattice and polymerization or
      depolymerization of the myosin filaments within the lattice. The time courses for
      these events are unknown. To gain insights into the adaptation process, we
      examined ASM mechanical properties and ultrastructural changes during adaptation.
      Step changes in length were applied to isolated bundles of ASM cells; changes in
      force, shortening velocity, and myosin filament mass were then quantified. A
      greater decrease in force was found following an acute decrease in length,
      compared with that of an acute increase in length. A decrease in myosin filament
      mass was also found with an acute decrease in length. The shortening velocity
      measured immediately after the length change was the same as that measured after
      the muscle had fully adapted to the new length. These observations can be
      explained by a model in which partial adaptation of the muscle leads to an
      intermediate state in which reconfiguration of the myofilament lattice occurred
      rapidly, followed by a relatively slow process of polymerization of myosin
      filaments within the lattice. The partially adapted intermediate state is perhaps
      more physiologically relevant than the fully adapted state seen under static
      conditions, and it simulates a more realistic behavior for ASM in vivo.

PMID- 17495119
TI  - Dose effects of modified alternate-day fasting regimens on in vivo cell
      proliferation and plasma insulin-like growth factor-1 in mice.
AB  - Reduced cell proliferation is associated with lower cancer risk. Alternate-day
      fasting (ADF), defined as alternating 24-h periods of ad libitum feeding and
      fasting, decreases cell proliferation. The effect of modified regimens of ADF on
      cell proliferation, however, has not been examined. This study measured the
      effects of modified ADF regimens on prostate and splenic T-cell proliferation and
      circulating insulin-like growth factor-1 (IGF-1) levels in mice. In a 4-wk study,
      24 male C57BL/6J mice were randomized to one of four interventions: 1) ADF-25%
      [25% calorie restriction (CR) on fast day], 2) ADF-50% (50% CR on fast day), 3)
      ADF-100% (100% CR on fast day), and 4) control. Body weight of the ADF-100% group
      was less (P < 0.005) than that of the ADF-25% and ADF-50% groups posttreatment.
      On the feast day, the ADF-100% and ADF-50% groups ate 85% and 45% more food,
      respectively, than controls, indicating a hyperphagic response to fasting.
      Proliferation rates of T-cells were 6% and 30% lower (P < 0.05) in the ADF-50%
      and ADF-100% groups, respectively, relative to controls. Prostate cell
      proliferation was reduced (P < 0.05) by 49% in the ADF-100% group, relative to
      controls, but did not change in the other groups. IGF-1 levels were reduced (P <
      0.05) by 40%, relative to controls, in the ADF-100% group. These findings confirm
      the beneficial effects of ADF-100% on cancer risk by decreasing cell
      proliferation and IGF-1 levels and suggest that modified ADF regimens comprising
      25-50% CR on the fast day do not replicate these effects.

PMID- 17495120
TI  - Exercise modulates platelet-nasopharyngeal carcinoma cell aggregation and
      subsequent tissue factor and matrix metalloproteinase activities.
AB  - Interaction between platelet and carcinoma cell contributes to pathogenesis of
      cancer-related thrombosis and metastasis. This study investigated whether
      physical exercise affects platelet-nasopharyngeal carcinoma cell (NPC)
      interaction and platelet-promoted tissue factor (TF) and matrix metalloproteinase
      (MMP) activities of NPC. Thirty sedentary men performed on three occasions
      moderate-intensity exercise [MIE, 60% maximal oxygen consumption (V(.)o(2max))
      for 40 min] and high-intensity exercise (HIE, up to V(.)o(2max)), with and
      without warm-up exercise (WUE, 60% V(.)o(2max) for 20 min) on a bicycle
      ergometer. Before and immediately after exercise, platelet-NPC aggregation, the
      TF, MMP-2 and MMP-9 expressions and activities, and TF pathway inhibitor (TFPI)
      and tissue inhibitor of MMP-1 levels of NPC and platelet were measured. The
      results of this study demonstrated that HIE enhanced platelet-NPC aggregation in
      the presence of fibrinogen and was accompanied by increased platelet-promoted TF
      activity, expression of NPC, decreased platelet-promoted MMP-2 and MMP-9
      activities, and TFPI release of NPC, whereas these alterations to HIE on platelet
      NPC interactions were ameliorated by WUE pretreatment. Conversely, MIE reduced
      the formation of platelet-NPC aggregates, but did not change the TF, TFPI, MMP-2,
      MMP-9, tissue inhibitor of MMP activities, and/or levels of NPC mediated by
      platelet. It is concluded that HIE may enhance aggregation and coagulation and
      reduce MMP bioactivity related to platelet-NPC interactions, by raising the
      binding affinity to fibrinogen and TF activity and expression and lowering TFPI
      release and MMP-2 and -9 activities. These effects on HIE diminish after WUE.
      However, MIE minimizes the risk of thrombosis induced by platelet-NPC
      interactions.

PMID- 17495121
TI  - CO2 relaxes parenchyma in the liquid-filled rat lung.
AB  - CO(2) regulation of lung compliance is currently explained by pH- and CO(2)
      dependent changes in alveolar surface forces and bronchomotor tone. We
      hypothesized that in addition to, but independently of, those mechanisms, the
      parenchyma tissue responds to hypercapnia and hypocapnia by relaxing and
      contracting, respectively, thereby improving local matching of ventilation (Va)
      to perfusion (Q). Twenty adult rats were slowly ventilated with modified Krebs
      solution (rate = 3 min(-1), 37 degrees C, open chest) to produce unperfused
      living lung preparations free of intra-airway surface forces. The solution was
      gassed with 21% O(2), balance N(2), and CO(2) varied to produce alveolar
      hypocapnia (Pco(2) = 26.1 +/- 2.4 mmHg, pH = 7.56 +/- 0.04) or hypercapnia
      (Pco(2) = 55.0 +/- 2.3 mmHg, pH = 7.23 +/- 0.02). The results show that lung
      recoil, as indicated from airway pressure measured during a breathhold following
      a large volume inspiration, is reduced approximately 30% when exposed to
      hypercapnia vs. hypocapnia (P < 0.0001, paired t-test), but stress relaxation and
      flow-dependent airway resistance were unaltered. Increasing CO(2) from hypo- to
      hypercapnic levels caused a substantial, significant decrease in the quasi-static
      pressure-volume relationship, as measured after inspiration and expiration of
      several tidal volumes, but hysteresis was unaltered. Furthermore, addition of the
      glycolytic inhibitor NaF abolished CO(2) effects on lung recoil. The results
      suggest that lung parenchyma tissue relaxation, arising from active elements in
      response to increasing alveolar CO(2), is independent of (and apparently in
      parallel with) passive tissue elements and may actively contribute to Va/Q
      matching.

PMID- 17495122
TI  - Estimating changes in mean body temperature for humans during exercise using core
      and skin temperatures is inaccurate even with a correction factor.
AB  - Changes in mean body temperature (DeltaT(b)) estimated by the traditional two
      compartment model of "core" and "shell" temperatures and an adjusted two
      compartment model incorporating a correction factor were compared with values
      derived by whole body calorimetry. Sixty participants (31 men, 29 women) cycled
      at 40% of peak O(2) consumption for 60 or 90 min in the Snellen calorimeter at 24
      or 30 degrees C. The core compartment was represented by esophageal, rectal
      (T(re)), and aural canal temperature, and the shell compartment was represented
      by a 12-point mean skin temperature (T(sk)). Using T(re) and conventional core-to
      shell weightings (X) of 0.66, 0.79, and 0.90, mean DeltaT(b) estimation error
      (with 95% confidence interval limits in parentheses) for the traditional model
      was -95.2% (-83.0, -107.3) to -76.6% (-72.8, -80.5) after 10 min and -47.2% (
      40.9, -53.5) to -22.6% (-14.5, -30.7) after 90 min. Using T(re), X = 0.80, and a
      correction factor (X(0)) of 0.40, mean DeltaT(b) estimation error for the
      adjusted model was +9.5% (+16.9, +2.1) to -0.3% (+11.9, -12.5) after 10 min and
      +15.0% (+27.2, +2.8) to -13.7% (-4.2, -23.3) after 90 min. Quadratic analyses of
      calorimetry DeltaT(b) data was subsequently used to derive best-fitting values of
      X for both models and X(0) for the adjusted model for each measure of core
      temperature. The most accurate model at any time point or condition only
      accounted for 20% of the variation observed in DeltaT(b) for the traditional
      model and 56% for the adjusted model. In conclusion, throughout exercise the
      estimation of DeltaT(b) using any measure of core temperature together with mean
      skin temperature irrespective of weighting is inaccurate even with a correction
      factor customized for the specific conditions.

PMID- 17495123
TI  - The apneic threshold during non-REM sleep in dogs: sensitivity of carotid body
      vs. central chemoreceptors.
AB  - The relative importance of peripheral vs. central chemoreceptors in causing
      apnea/unstable breathing during sleep is unresolved. This has never been tested
      in an unanesthetized preparation with intact carotid bodies. We studied three
      unanesthetized dogs during normal sleep in a preparation in which intact carotid
      body chemoreceptors could be reversibly isolated from the systemic circulation
      and perfused. Apneic thresholds and the CO(2) reserve (end-tidal Pco(2) eupneic -
      end-tidal Pco(2) apneic threshold) were determined using a pressure support
      ventilation technique. Dogs were studied when both central and peripheral
      chemoreceptors sensed transient hypocapnia induced by the pressure support
      ventilation and again with carotid body isolation such that only the central
      chemoreceptors sensed the hypocapnia. We observed that the CO(2) reserve was
      congruent with4.5 Torr when the carotid chemoreceptors sensed the transient
      hypocapnia but more than doubled (>9 Torr) when only the central chemoreceptors
      sensed hypocapnia. Furthermore, the expiratory time prolongations observed when
      only central chemoreceptors were exposed to hypocapnia differed from those
      obtained when both the central and peripheral chemoreceptors sensed the
      hypocapnia in that they 1) were substantially shorter for a given reduction in
      end-tidal Pco(2), 2) showed no stimulus: response relationship with increasing
      hypocapnia, and 3) often occurred at a time (>45 s) beyond the latency expected
      for the central chemoreceptors. These findings agree with those previously
      obtained using an identical pressure support ventilation protocol in carotid body
      denervated sleeping dogs (Nakayama H, Smith CA, Rodman JR, Skatrud JB, Dempsey
      JA. J Appl Physiol 94: 155-164, 2003). We conclude that hypocapnia sensed at the
      carotid body chemoreceptor is required for the initiation of apnea following a
      transient ventilatory overshoot in non-rapid eye movement sleep.

PMID- 17495124
TI  - Flavonoid glycosides are not transported by the human Na+/glucose transporter
      when expressed in Xenopus laevis oocytes, but effectively inhibit electrogenic
      glucose uptake.
AB  - There is controversy as to whether intestinal absorption of glycosylated
      flavonoids, and particularly quercetin glycosides, involves their uptake in
      intact form via the human sodium-coupled glucose transporter hSGLT1. We here
      describe studies using Xenopus oocytes that express hSGLT1 and the two-electrode
      voltage clamp technique to determine the transport characteristics of a variety
      of flavonoids carrying glucose residues at different positions as well as of
      their aglycones (altogether 27 compounds). Neither quercetin, luteolin, apigenin,
      naringenin, pelarginidin, daidzein, or genistein, nor any of their glycosylated
      derivatives generated significant transport currents. However, the inward current
      evoked by 1 mM of the hSGLT1 substrate alpha-methyl-D-glucopyranoside was
      potently reduced by the simultaneous application of not only various flavonoid
      glycosides but also by some aglycones. The inhibitory potency remained unchanged
      when the attached glucose was replaced by galactose, suggesting that these
      residues may bind to SGLT1. Kinetic analysis by Dixon plots revealed inhibition
      of competitive type with high affinities, particularly when the glucose was
      attached to the position 4' of the aromatic ring of the flavonoids. The
      affinities became lower when the glucose was attached to a different position.
      Unexpectedly, the aglycone form of luteolin also inhibited the transport
      competitively with high affinity. These data show that hSGLT1 does not transport
      any of the flavonoids and seems therefore not involved in their intestinal
      absorption. However, not only glycosylated but also a few nonglycosylated
      flavonoids show a structure-dependent capability for effective inhibition of
      SGLT1.

PMID- 17495125
TI  - Transport of paraquat by human organic cation transporters and multidrug and
      toxic compound extrusion family.
AB  - Paraquat (N,N-dimethyl-4-4'-bipiridinium; PQ), a widely used herbicide, when
      ingested accidentally or intentionally can cause major organ toxicities in lung,
      liver, and kidney. Because PQ is primarily eliminated in the kidney, renal
      elimination, including tubular transport, plays a critical role in controlling
      systemic exposure to the herbicide. The goal of this study was to determine the
      molecular identities of the transporters involved in the renal elimination of PQ.
      Using stably transfected human embryonic kidney (HEK)-293 cells, we examined the
      role of human organic cation transporters (hOCTs, SLC22A1-3) and human multidrug
      and toxic compound extrusion (hMATE)1 in the cellular accumulation and
      cytotoxicity of PQ. We found that overexpression of hOCT2 but not hOCT1 and hOCT3
      in HEK-293 cells significantly enhanced the accumulation and cytotoxicity of PQ (
      fold increase for uptake was 12 +/- 0.5, p < 0.01; -fold increase of cytotoxicity
      was 18 +/- 1.5, p < 0.001). The kinetics of PQ transport was altered in cells
      expressing a genetic polymorphism of hOCT2 (A270S) in comparison with those
      expressing the reference hOCT2. In addition, the cellular accumulation and
      cytotoxicity of PQ were also enhanced in cells expressing hMATE1 (-fold increase
      for uptake was 18 +/- 3.7, p < 0.0001; -fold increase of cytotoxicity was 5.7 +/-
      0.5, p < 0.0001). These results suggest that hOCT2 and hMATE1 mediate PQ
      transport. These transporters may play an important role in the accumulation and
      renal excretion of PQ, and they may serve as molecular targets for the prevention
      and treatment of PQ-induced nephrotoxicity.

PMID- 17495126
TI  - Testing the bipartite model of the sulfonylurea receptor binding site: binding of
      A-, B-, and A + B-site ligands.
AB  - ATP-sensitive K(+) (K(ATP)) channels are composed of pore-forming subunits
      (Kir6.x) and of regulatory subunits, the sulfonylurea receptors (SURx). Subtypes
      of K(ATP) channels are expressed in different organs. The sulfonylureas and
      glinides (insulinotropes) close the K(ATP) channel in pancreatic beta-cells and
      stimulate insulin secretion. The insulinotrope binding site of the pancreatic
      channel (Kir6.2/SUR1) consists of two overlapping (sub)-sites, site A, located on
      SUR1 and containing Ser1237 (which in SUR2 is replaced by Tyr1206), and site B,
      formed by SUR1 and Kir6.2. Insulinotropes bind to the A-, B-, or A + B-site(s)
      and are grouped accordingly. A-ligands are highly selective in closing the
      pancreatic channel, whereas B-ligands are nonselective and insensitive to the
      mutation S1237Y. We have examined the binding of insulinotropes representative of
      the three groups in [(3)H]glibenclamide competition experiments to determine the
      contribution of Kir6.x to binding affinity, the effect of the mutation Y1206S in
      site A of SUR2, and the subtype selectivity of the compounds. The results show
      that the bipartite nature of the SUR1 binding site applies also to SUR2. Kir6.2
      as part of the B-site may interact directly or allosterically with structural
      elements common to all insulinotropes, i.e., the negative charge and/or the
      adjacent phenyl ring. The B-site confers a moderate subtype selectivity on B
      ligands. The affinity of B-ligands is altered by the mutation SUR2(Y1206S),
      suggesting that the mutation affects the binding chamber of SUR2 as a whole or
      subsite A, including the region where the subsites overlap.

PMID- 17495127
TI  - CJ-023,423, a novel, potent and selective prostaglandin EP4 receptor antagonist
      with antihyperalgesic properties.
AB  - The prostaglandin (PG) EP(4) receptor subtype is expressed by peripheral sensory
      neurons. Although a potential role of EP(4) receptor in pain has been suggested,
      a limited number of selective ligands have made it difficult to explore the
      physiological functions of EP(4) or its potential as a new analgesic target.
      Here, we describe the in vitro and in vivo pharmacology of a novel EP(4) receptor
      antagonist, N-[({2-[4-(2-ethyl-4,6-dimethyl-1H-imidazo [4,5-c] pyridin-1-yl)
      phenyl]ethyl}amino) carbonyl]-4-methylbenzenesulfonamide (CJ-023,423). In vitro,
      CJ-023,423 inhibits [(3)H]PGE(2) binding to both human and rat EP(4) receptors
      with K(i) of 13 +/- 4 and 20 +/- 1 nM, respectively. CJ-023,423 is highly
      selective for the human EP(4) receptor over other human prostanoid receptor
      subtypes. It also inhibits PGE(2)-evoked elevation in intracellular cAMP at the
      human and rat EP(4) receptors with pA(2) of 8.3 +/- 0.03 and 8.2 +/- 0.2 nM,
      respectively. In vivo, oral administration of CJ-023,423 significantly reduces
      thermal hyperalgesia induced by intraplantar injection of PGE(2) (ED(50) = 12.8
      mg/kg). CJ-023,423 is also effective in models of acute and chronic inflammatory
      pain. CJ-023,423 significantly reduces mechanical hyperalgesia in the carrageenan
      model. Furthermore, CJ-023,423 significantly reverses complete Freund's adjuvant
      induced chronic inflammatory pain response. Taken together, the present data
      indicate that CJ-023,423, a highly potent and selective antagonist of both human
      and rat EP(4) receptors, produces antihyperalgesic effects in animal models of
      inflammatory pain. Thus, specific blockade of the EP(4) receptor signaling may
      represent a novel therapeutic approach for the treatment of inflammatory pain.

PMID- 17495128
TI  - Tumor necrosis factor (TNF)-soluble high-affinity receptor complex as a TNF
      antagonist.
AB  - A novel high-affinity inhibitor of tumor necrosis factor (TNF) is described,
      which is created by the fusion of the extracellular domains of TNF-binding
      protein 1 (TBP-1) to both the alpha and beta chains of an inactive version of the
      heterodimeric protein hormone, human chorionic gonadotropin. The resulting
      molecule, termed TNF-soluble high-affinity receptor complex (SHARC), self
      assembles into a heterodimeric protein containing two functional TBP-1 moieties.
      The TNF-SHARC is a potent inhibitor of TNF-alpha bioactivity in vitro and has a
      prolonged pharmacokinetic profile compared with monomeric TBP-1 in vivo.
      Consistent with the long half-life, the duration of action in an
      lipopolysaccharide-mediated proinflammatory mouse model is prolonged similarly.
      In a collagen-induced arthritis mouse model, this molecule demonstrates improved
      efficacy over monomeric TBP-1. Based on these results, we demonstrated that
      inactivated heterodimeric protein hormones are flexible and efficient scaffolds
      for the creation of soluble high-affinity receptor complexes.

PMID- 17495129
TI  - Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis:
      clinical and therapeutic implications.
AB  - Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis in vitro. We
      have now examined whether PF4 regulates megakaryopoiesis in vivo by studying PF4
      knockout mice and transgenic mice that overexpress human (h) PF4. Steady-state
      platelet count and thrombocrit in these animals was inversely related to platelet
      PF4 content. Growth of megakaryocyte colonies was also inversely related to
      platelet PF4 content. Function-blocking anti-PF4 antibody reversed this
      inhibition of megakaryocyte colony growth, indicating the importance of local PF4
      released from developing megakaryocytes. The effect of megakaryocyte damage and
      release of PF4 on 5-fluorouracil-induced marrow failure was then examined.
      Severity of thrombocytopenia and time to recovery of platelet counts were
      inversely related to initial PF4 content. Recovery was faster and more extensive,
      especially in PF4-overexpressing mice, after treatment with anti-PF4 blocking
      antibodies, suggesting a means to limit the duration of such a chemotherapy
      induced thrombocytopenia, especially in individuals with high endogenous levels
      of PF4. We found that approximately 8% of 250 healthy adults have elevated (> 2
      times average) platelet PF4 content. These individuals with high levels of
      platelet PF4 may be especially sensitive to developing thrombocytopenia after
      bone marrow injury and may benefit from approaches that block the effects of
      released PF4.

PMID- 17495130
TI  - Eosinophils contribute to innate antiviral immunity and promote clearance of
      respiratory syncytial virus.
AB  - Eosinophils are recruited to the lungs in response to respiratory syncytial virus
      (RSV) infection; however, their role in promoting antiviral host defense remains
      unclear. Here, we demonstrate that eosinophils express TLRs that recognize viral
      nucleic acids, are activated and degranulate after single-stranded RNA (ssRNA)
      stimulation of the TLR-7-MyD88 pathway, and provide host defense against RSV that
      is MyD88 dependent. In contrast to wild-type mice, virus clearance from lung
      tissue was more rapid in hypereosinophilic (interleukin-5 transgenic) mice.
      Transfer of wild-type but not MyD88-deficient eosinophils to the lungs of RSV
      infected wild-type mice accelerated virus clearance and inhibited the development
      of airways hyperreactivity. Similar responses were observed when infected
      recipient mice were MyD88 deficient. Eosinophils isolated from infected
      hypereosinophilic MyD88-sufficient but not MyD88-deficient mice expressed greater
      amounts of IFN regulatory factor (IRF)-7 and eosinophil-associated ribonucleases
      EAR-1 and EAR-2. Hypereosinophilia in the airways of infected mice also
      correlated with increased expression of IRF-7, IFN-beta, and NOS-2, and
      inhibition of NO production with the NOS-2 inhibitor L-NMA partially reversed the
      accelerated virus clearance promoted by eosinophils. Collectively, our results
      demonstrate that eosinophils can protect against RSV in vivo, as they promote
      virus clearance and may thus limit virus-induced lung dysfunction.

PMID- 17495131
TI  - AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest,
      apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II
      inhibitor in human acute leukemia cells in vitro and in vivo.
AB  - Aurora kinases play an important role in chromosome alignment, segregation, and
      cytokinesis during mitosis. We have recently shown that hematopoietic malignant
      cells including those from acute myeloid leukemia (AML) and acute lymphoblastic
      leukemia (ALL) aberrantly expressed Aurora A and B kinases, and ZM447439, a
      potent inhibitor of Aurora kinases, effectively induced growth arrest and
      apoptosis of a variety of leukemia cells. The present study explored the effect
      of AZD1152, a highly selective inhibitor of Aurora B kinase, on various types of
      human leukemia cells. AZD1152 inhibited the proliferation of AML lines (HL-60,
      NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute
      eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia
      K562 cells with an IC50 ranging from 3 nM to 40 nM, as measured by thymidine
      uptake on day 2 of culture. These cells had 4N/8N DNA content followed by
      apoptosis, as measured by cell-cycle analysis and annexin V staining,
      respectively. Of note, AZD1152 synergistically enhanced the antiproliferative
      activity of vincristine, a tubulin depolymerizing agent, and daunorubicin, a
      topoisomerase II inhibitor, against the MOLM13 and PALL-2 cells in vitro.
      Furthermore, AZD1152 potentiated the action of vincristine and daunorubicin in a
      MOLM13 murine xenograft model. Taken together, AZD1152 is a promising new agent
      for treatment of individuals with leukemia. The combined administration of
      AZD1152 and conventional chemotherapeutic agent to patients with leukemia
      warrants further investigation.

PMID- 17495132
TI  - Anti factor H autoantibodies block C-terminal recognition function of factor H in
      hemolytic uremic syndrome.
AB  - The atypical form of the kidney disease hemolytic uremic syndrome (aHUS) is
      associated with defective complement regulation. In addition to mutations in
      complement regulators, factor H (FH)-specific autoantibodies have been reported
      for aHUS patients. The aim of the present study was to understand the role of
      these autoantibodies in aHUS. First, the binding sites of FH autoantibodies from
      5 unrelated aHUS patients were mapped using recombinant FH fragments and
      competitor antibodies. For all 5 autoantibodies, the binding site was localized
      to the FH C-terminus. In a functional assay, isolated patient IgG inhibited FH
      binding to C3b. In addition, autoantibody-positive patients' plasma caused
      enhanced hemolysis of sheep erythrocytes, which was reversed by adding FH in
      excess. These results suggest that aHUS-associated FH autoantibodies mimic the
      effect of C-terminal FH mutations, as they inhibit the regulatory function of FH
      at cell surfaces by blocking its C-terminal recognition region.

PMID- 17495133
TI  - The unexpected effect of cyclosporin A on CD56+CD16- and CD56+CD16+ natural
      killer cell subpopulations.
AB  - Cyclosporin A (CSA) is commonly used to prevent graft-versus-host disease. The
      influence of CSA on T-cell function has been extensively investigated; however,
      the effect of CSA on natural killer (NK) cells is less understood. NK cells were
      cultured with IL-2 and IL-15 with and without CSA for 1 week. Compared with
      controls, CSA-treated cultures showed fewer CD56(+)CD16(+)KIR(+) NK cells and a
      reciprocal increase in CD56(+)CD16(-)KIR(-) cells. These changes were due mainly
      to a reduced proliferation of the CD56(dim) NK-cell subpopulation and a relative
      resistance of CD56(bright) NK cells to CSA. Following coculture with K562
      targets, CSA-exposed NK cells differed from controls and lacked Ca(2+)
      oscillations, nuclear factor of activated T cells (NFAT) dephosphorylation, and
      NFAT nuclear translocation. NK cells cultured in CSA retained cytotoxicity
      against K562, Raji, and KIR ligand-expressing lymphoblastoid cells. NK cells
      cultured in CSA showed increases in NKp30 and reductions in NKp44 and NKG2D.
      Following IL-12 and IL-18 stimulation, CSA-treated NK cells showed more IFN-gamma
      producing cells. Using in vitro NK-cell differentiation, progenitor cells gave
      rise to more CD56(+)KIR(-) NK cells in the presence of CSA than controls.
      Collectively, these studies show that CSA influences NK-cell function and
      phenotype, which may have important implications for graft-versus-leukemia
      effects.

PMID- 17495136
TI  - Physiology. Proteasomes keep the circadian clock ticking.

PMID- 17495135
TI  - The immune response to lentiviral-delivered transgene is modulated in vivo by
      transgene-expressing antigen-presenting cells but not by CD4+CD25+ regulatory T
      cells.
AB  - Systemic delivery of lentiviral vector (LV) in immunocompetent mice leads to
      efficient in vivo cell transduction and expression of the encoded protein under
      the control of the ubiquitous promoter of human cytomegalovirus (CMV). However,
      antitransgene immune response results in clearance of transduced cells 4 weeks
      after injection. T regulatory cells (Tregs), which have been demonstrated to
      control immune responses in vivo, were tested for their ability to suppress
      antitransgene response leading to stable long-term expression. Adoptive transfer
      of natural CD4(+)CD25(+) Tregs (nTregs) isolated from wild type (wt) mice or from
      transgene tolerant transgenic (tg) mice did not suppress the antitransgene immune
      response after LV delivery. These data demonstrate that neither increasing the
      endogenous pool of natural Tregs nor transferring nTregs selected in a transgene
      expressing thymus can modulate the immune response and mediate sustained
      transgene expression. Conversely, adoptive transfer of antigen-presenting cells
      (APCs) isolated from transgene-tolerant tg mice efficiently reduced the immune
      response leading to stable LV-encoded protein expression in vivo. Reduction of
      CD8(+) effector T cells was observed in LV-treated mice coinjected with transgene
      expressing APCs compared with control mice. These data indicate that
      antitransgene immune response can be modulated by transgene-expressing APCs
      possibly through deletion of effector T cells.

PMID- 17495134
TI  - Identification of genomic classifiers that distinguish induction failure in T
      lineage acute lymphoblastic leukemia: a report from the Children's Oncology
      Group.
AB  - The clinical and cytogenetic features associated with T-cell acute lymphoblastic
      leukemia (T-ALL) are not predictive of early treatment failure. Based on the
      hypothesis that microarrays might identify patients who fail therapy, we used the
      Affymetrix U133 Plus 2.0 chip and prediction analysis of microarrays (PAM) to
      profile 50 newly diagnosed patients who were treated in the Children's Oncology
      Group (COG) T-ALL Study 9404. We identified a 116-member genomic classifier that
      could accurately distinguish all 6 induction failure (IF) cases from 44 patients
      who achieved remission; network analyses suggest a prominent role for genes
      mediating cellular quiescence. Seven genes were similarly upregulated in both the
      genomic classifier for IF patients and T-ALL cell lines having acquired
      resistance to neoplastic agents, identifying potential target genes for further
      study in drug resistance. We tested whether our classifier could predict IF
      within 42 patient samples obtained from COG 8704 and, using PAM to define a
      smaller classifier for the U133A chip, correctly identified the single IF case
      and patients with persistently circulating blasts. Genetic profiling may identify
      T-ALL patients who are likely to fail induction and for whom alternate treatment
      strategies might be beneficial.

PMID- 17495137
TI  - Atmosphere. Deglaciation mysteries.

PMID- 17495138
TI  - Missing mass in collisional debris from galaxies.
AB  - Recycled dwarf galaxies can form in the collisional debris of massive galaxies.
      Theoretical models predict that, contrary to classical galaxies, these recycled
      galaxies should be free of nonbaryonic dark matter. By analyzing the observed gas
      kinematics of such recycled galaxies with the help of a numerical model, we
      demonstrate that they do contain a massive dark component amounting to about
      twice the visible matter. Staying within the standard cosmological framework,
      this result most likely indicates the presence of large amounts of unseen,
      presumably cold, molecular gas. This additional mass should be present in the
      disks of their progenitor spiral galaxies, accounting for a substantial part of
      the so-called missing baryons.

PMID- 17495139
TI  - Marine radiocarbon evidence for the mechanism of deglacial atmospheric CO2 rise.
AB  - We reconstructed the radiocarbon activity of intermediate waters in the eastern
      North Pacific over the past 38,000 years. Radiocarbon activity paralleled that of
      the atmosphere, except during deglaciation, when intermediate-water values fell
      by more than 300 per mil. Such a large decrease requires a deglacial injection of
      very old waters from a deep-ocean carbon reservoir that was previously well
      isolated from the atmosphere. The timing of intermediate-water radiocarbon
      depletion closely matches that of atmospheric carbon dioxide rise and effectively
      traces the redistribution of carbon from the deep ocean to the atmosphere during
      deglaciation.

PMID- 17495140
TI  - Environment. Tropical forests and climate policy.

PMID- 17495142
TI  - Climate change. IPCC report lays out options for taming greenhouse gases.

PMID- 17495141
TI  - Your genes and privacy.

PMID- 17495143
TI  - Climate change. Meanwhile, back in Washington...

PMID- 17495144
TI  - Physics. All paired up but unable to flow, atoms strain key conceptual link.

PMID- 17495145
TI  - AIDS drugs. Brazil, Thailand override big pharma patents.

PMID- 17495146
TI  - Gender equity. Women are scarce in new NAS class.

PMID- 17495147
TI  - Budget policy. U.S. science adviser tells researchers to look elsewhere.

PMID- 17495148
TI  - Biodiversity. The ultimate life list.

PMID- 17495149
TI  - French science. Researchers await changes--and clashes--after Sarkozy's victory.

PMID- 17495150
TI  - Genome-wide association. Closing the net on common disease genes.

PMID- 17495151
TI  - Ecology. Back to the no-analog future?

PMID- 17495153
TI  - "Overshoot" scenarios and climate change.

PMID- 17495152
TI  - Neurological disorders. The mystery of the missing smile.

PMID- 17495154
TI  - CO2 emissions: a piece of the pie.

PMID- 17495155
TI  - Biobanking primer: down to basics.

PMID- 17495156
TI  - Medicine. Reestablishing the researcher-patient compact.

PMID- 17495157
TI  - Ocean science. Biomixing of the oceans?

PMID- 17495158
TI  - Planetary science. A local wiggle in the turbulent interstellar magnetic field.

PMID- 17495159
TI  - Immunology. Keeping a tight leash on Notch.

PMID- 17495160
TI  - Geophysics. Slippery when hot.

PMID- 17495161
TI  - Planetary science. Titan's organic factory.

PMID- 17495162
TI  - Cell signaling. The art of the soluble.

PMID- 17495163
TI  - Global desertification: building a science for dryland development.
AB  - In this millennium, global drylands face a myriad of problems that present tough
      research, management, and policy challenges. Recent advances in dryland
      development, however, together with the integrative approaches of global change
      and sustainability science, suggest that concerns about land degradation,
      poverty, safeguarding biodiversity, and protecting the culture of 2.5 billion
      people can be confronted with renewed optimism. We review recent lessons about
      the functioning of dryland ecosystems and the livelihood systems of their human
      residents and introduce a new synthetic framework, the Drylands Development
      Paradigm (DDP). The DDP, supported by a growing and well-documented set of tools
      for policy and management action, helps navigate the inherent complexity of
      desertification and dryland development, identifying and synthesizing those
      factors important to research, management, and policy communities.

PMID- 17495164
TI  - Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene
      LRF.
AB  - Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors,
      which subsequently differentiate into B and T lymphocytes. Here we show that the
      proto-oncogene LRF plays an essential role in the B versus T lymphoid cell-fate
      decision. We demonstrate that LRF is key for instructing early lymphoid
      progenitors in mice to develop into B lineage cells by repressing T cell
      instructive signals produced by the cell-fate signal protein, Notch. We propose a
      new model for lymphoid lineage commitment, in which LRF acts as a master
      regulator of the cell's determination of B versus T lineage.

PMID- 17495165
TI  - Pairing without superfluidity: the ground state of an imbalanced Fermi mixture.
AB  - We used radio-frequency spectroscopy to study pairing in the normal and
      superfluid phases of a strongly interacting Fermi gas with imbalanced spin
      populations. At high spin imbalances, the system does not become superfluid even
      at zero temperature. In this normal phase, full pairing of the minority atoms was
      observed. Hence, mismatched Fermi surfaces do not prevent pairing but can quench
      the superfluid state, thus realizing a system of fermion pairs that do not
      condense even at the lowest temperature.

PMID- 17495166
TI  - The process of tholin formation in Titan's upper atmosphere.
AB  - Titan's lower atmosphere has long been known to harbor organic aerosols (tholins)
      presumed to have been formed from simple molecules, such as methane and nitrogen
      (CH4 and N2). Up to now, it has been assumed that tholins were formed at
      altitudes of several hundred kilometers by processes as yet unobserved. Using
      measurements from a combination of mass/charge and energy/charge spectrometers on
      the Cassini spacecraft, we have obtained evidence for tholin formation at high
      altitudes (approximately 1000 kilometers) in Titan's atmosphere. The observed
      chemical mix strongly implies a series of chemical reactions and physical
      processes that lead from simple molecules (CH4 and N2) to larger, more complex
      molecules (80 to 350 daltons) to negatively charged massive molecules
      (approximately 8000 daltons), which we identify as tholins. That the process
      involves massive negatively charged molecules and aerosols is completely
      unexpected.

PMID- 17495167
TI  - The orientation of the local interstellar magnetic field.
AB  - The orientation of the local interstellar magnetic field introduces asymmetries
      in the heliosphere that affect the location of heliospheric radio emissions and
      the streaming direction of ions from the termination shock of the solar wind. We
      combined observations of radio emissions and energetic particle streaming with
      extensive three-dimensional magnetohydrodynamic computer simulations of magnetic
      field draping over the heliopause to show that the plane of the local
      interstellar field is approximately 60 degrees to 90 degrees from the galactic
      plane. This finding suggests that the field orientation in the Local Interstellar
      Cloud differs from that of a larger-scale interstellar magnetic field thought to
      parallel the galactic plane.

PMID- 17495168
TI  - Ultralow friction of carbonate faults caused by thermal decomposition.
AB  - High-velocity weakening of faults may drive fault motion during large
      earthquakes. Experiments on simulated faults in Carrara marble at slip rates up
      to 1.3 meters per second demonstrate that thermal decomposition of calcite due to
      frictional heating induces pronounced fault weakening with steady-state friction
      coefficients as low as 0.06. Decomposition produces particles of tens of
      nanometers in size, and the ultralow friction appears to be associated with the
      flash heating on an ultrafine decomposition product. Thus, thermal decomposition
      may be an important process for the dynamic weakening of faults.

PMID- 17495169
TI  - GRACE gravity data constrain ancient ice geometries and continental dynamics over
      Laurentia.
AB  - The free-air gravity trend over Canada, derived from the Gravity Recovery and
      Climate Experiment (GRACE) satellite mission, robustly isolates the gravity
      signal associated with glacial isostatic adjustment (GIA) from the longer-time
      scale mantle convection process. This trend proves that the ancient Laurentian
      ice complex was composed of two large domes to the west and east of Hudson Bay,
      in accord with one of two classes of earlier reconstructions. Moreover, GIA
      models that reconcile the peak rates contribute approximately 25 to approximately
      45% to the observed static gravity field, which represents an important boundary
      condition on the buoyancy of the continental tectosphere.

PMID- 17495170
TI  - The role of wheat awns in the seed dispersal unit.
AB  - The dispersal unit of wild wheat bears two pronounced awns that balance the unit
      as it falls. We discovered that the awns are also able to propel the seeds on and
      into the ground. The arrangement of cellulose fibrils causes bending of the awns
      with changes in humidity. Silicified hairs that cover the awns allow propulsion
      of the unit only in the direction of the seeds. This suggests that the dead
      tissue is analogous to a motor. Fueled by the daily humidity cycle, the awns
      induce the motility required for seed dispersal.

PMID- 17495171
TI  - Bat flight generates complex aerodynamic tracks.
AB  - The flapping flight of animals generates an aerodynamic footprint as a time
      varying vortex wake in which the rate of momentum change represents the
      aerodynamic force. We showed that the wakes of a small bat species differ from
      those of birds in some important respects. In our bats, each wing generated its
      own vortex loop. Also, at moderate and high flight speeds, the circulation on the
      outer (hand) wing and the arm wing differed in sign during the upstroke,
      resulting in negative lift on the hand wing and positive lift on the arm wing.
      Our interpretations of the unsteady aerodynamic performance and function of
      membranous-winged, flapping flight should change modeling strategies for the
      study of equivalent natural and engineered flying devices.

PMID- 17495172
TI  - Emotional stimulation alters olfactory sensitivity and odor judgment.
AB  - Emotions have a strong influence on the perception of visual and auditory
      stimuli. Only little is known about the relation between emotional stimulation
      and olfactory functions. The present study investigated the relationship between
      the presentation of affective pictures, olfactory functions, and sex. Olfactory
      performance was assessed in 32 subjects (16 male). Olfactory sensitivity was
      significantly reduced following unpleasant picture presentation for all subjects
      and following pleasant picture presentation for male subjects only. Pleasantness
      and intensity ratings of a neutral suprathreshold odor were related to the
      valence of the pictures: After unpleasant picture presentation, the odor was
      rated as less pleasant and more intense, whereas viewing positive pictures
      induced a significant increase in reported odor pleasantness. We conclude that
      inducing a negative emotional state reduces olfactory sensitivity. A relation to
      functional deviations within the primary olfactory cortices is discussed.

PMID- 17495173
TI  - Trying to detect taste in a tasteless solution: modulation of early gustatory
      cortex by attention to taste.
AB  - Selective attention is thought to be associated with enhanced processing in
      modality-specific cortex. We used functional magnetic resonance imaging to
      evaluate brain response during a taste detection task. We demonstrate that trying
      to detect the presence of taste in a tasteless solution results in enhanced
      activity in insula and overlying operculum. The same task does not recruit
      orbitofrontal cortex (OFC). Instead, the OFC responds preferentially during
      receipt of an unpredicted taste stimulus. These findings demonstrate functional
      specialization of taste cortex in which the insula and the overlying operculum
      are recruited during taste detection and selective attention to taste, and the
      OFC is recruited during receipt of an unpredicted taste stimulus.

PMID- 17495174
TI  - Head and neck cancer: dedicated FDG PET/CT protocol for detection--phantom and
      initial clinical studies.
AB  - PURPOSE: To retrospectively compare the sensitivity of a dedicated fluorine 18
      fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography
      (CT) protocol versus a standard whole-body PET/CT protocol for detection of head
      and neck cancer, with biopsy and follow-up as reference standards. MATERIALS AND
      METHODS: Institutional review board approval and informed consent were obtained
      for this HIPAA-compliant study. Dedicated and standard PET/CT protocols were
      performed in a phantom and in 55 patients suspected of having head and neck
      cancer (28 men, 27 women; age range, 21-79 years). The neck phantom contained
      four 4.4-9.8-mm-diameter spheres. Standard protocol consisted of a midcranium to
      proximal thigh emission scan of 2-4 minutes per bed position. Dedicated protocol
      was an 8-minute head and neck scan. Reconstructed field of view and pixel size,
      respectively, were 30 cm and 2.34 mm for the dedicated and 50 cm and 3.91 mm for
      the standard protocol. FDG uptake was evaluated visually and semiquantitatively
      by using standardized uptake values (SUVs). Mean SUV was compared between
      dedicated and standard protocols with a t test modified for clustered sampling.
      Receiver operating characteristic (ROC) curves were calculated. A two-tailed P
      value was used. RESULTS: In the phantom study, a larger percentage difference
      (20%-27%) in sphere-to-background ratios with the dedicated than with the
      standard protocol was observed for 6.0-9.8-mm spheres. In the clinical study, a
      total of 149 lymph nodes were identified. Five malignant and six benign lymph
      nodes (mean diameter, 7.1 mm) were visually identified with the dedicated
      protocol only. SUVs with the dedicated protocol were significantly higher than
      those with the standard protocol (P<.001). Area under the ROC curve was 0.94 for
      the dedicated and 0.92 for the standard protocol (P=.56). CONCLUSION: FDG PET
      with either the standard or dedicated protocol was more sensitive than CT for
      evaluating head and neck lymph nodes. The dedicated protocol improved the
      detectability of smaller nodes.

PMID- 17495175
TI  - Renal artery stenosis in swine: feasibility of MR assessment of renal function
      during percutaneous transluminal angioplasty.
AB  - PURPOSE: To prospectively test--in a swine model of renal artery stenosis (RAS)-
      the hypothesis that magnetic resonance (MR) imaging can reveal changes in renal
      function at the time of percutaneous transluminal angioplasty (PTA). MATERIALS
      AND METHODS: In this animal care and use committee-approved study, high-grade
      unilateral RAS was surgically induced in six pigs. MR imaging at 3.0 T was used
      for intraprocedural assessment of the anatomic and physiologic changes induced by
      x-ray-guided PTA. With use of MR imaging, changes in single-kidney glomerular
      filtration rate, extraction fraction, and renal blood flow were assessed during
      PTA. The arterial diameter of stenosis before and after PTA was assessed by using
      conventional digital subtraction angiography. Mean changes in functional and
      anatomic parameters were compared by using the Wilcoxon signed rank test (alpha =
      .05). RESULTS: At digital subtraction angiography, the mean percentage of
      stenosis was 69% +/- 10 (standard deviation) before PTA and 26% +/- 10 after PTA
      (P<.03). Mean pre- and post-PTA extraction fraction values were 0.11 +/- 0.03 and
      0.19 +/- 0.06, respectively (P<.03). The mean single-kidney glomerular filtration
      rate before PTA, 19 mL/min +/- 13, increased to 41 mL/min +/- 33 after PTA
      (P<.03). There was no significant change in mean renal blood flow after PTA
      (P=.44). CONCLUSION: In swine, MR imaging can reveal changes in renal function
      after x-ray-guided PTA for unilateral RAS.

PMID- 17495176
TI  - Coronary CT angiography.
AB  - Owing to ongoing technical refinements and intense scientific and clinical
      evaluations, computed tomography (CT) of the heart has left the research realm
      and matured into a clinical application that is about to fulfill its promise to
      replace invasive cardiac catheterization in selected patient populations. CT
      coronary angiography is technically more challenging than other CT applications
      owing to the nature of its target, the continuously moving heart. Rapid technical
      developments in this field require constant adaptation of acquisition protocols.
      These challenges, however, are in no way insurmountable for users with knowledge
      of the general CT technique. The intent of this communication is to provide those
      interested in and involved with coronary CT angiography with a step-by-step
      "manual" describing the authors' approach to performing coronary CT angiography.
      Included are considerations regarding appropriate patient selection, patient
      medication, radiation protection, contrast enhancement, acquisition and
      reconstruction parameters, image display and analysis techniques, and the
      radiology report. The recommendations are based on the authors' experience, which
      spans the evolution of multi-detector row CT for cardiac applications, from its
      beginning to the advent of the most current generations of 64-section and dual
      source CT technologies, which they believe herald the entrance of this
      examination into routine clinical practice.

PMID- 17495177
TI  - Does two-segment image reconstruction at 64-section CT coronary angiography
      improve image quality and diagnostic accuracy?
AB  - PURPOSE: To prospectively evaluate the effect of single- versus two-segment image
      reconstruction on image quality and diagnostic accuracy at 64-section
      multidetector computed tomographic (CT) coronary angiography by using
      conventional coronary angiography as the reference standard. MATERIALS AND
      METHODS: The study design was approved by a human research committee; patients
      gave informed consent. The study was HIPAA compliant. Forty consecutive patients
      (22 men, 18 women; mean age, 61 years +/- 8 [standard deviation]) underwent both
      64-section multidetector CT coronary angiography and conventional angiography.
      All data sets were reconstructed by using single- and two-segment image
      reconstruction algorithms, with resulting temporal resolution of 82.5-165 msec.
      Two experienced observers independently evaluated image quality and signs of
      coronary artery disease. A five-level grading scheme was used to grade stenosis
      (0%, <50%, <70%, <99%, 100%) and image quality (1[unacceptable] to 5[excellent]).
      Interobserver correlation, Spearman correlation coefficients, and diagnostic
      accuracy were calculated. RESULTS: Six hundred coronary artery segments were
      visible on conventional angiograms, of which 560 (93.3%) were seen by using
      single-segment and 561 (93.5%) were seen by using two-segment image
      reconstruction (P=.35). Mean quality scores were not significantly different
      (P=.22) for single- (3.1 +/- 0.9) and two-segment (3.2 +/- 0.8) reconstruction.
      Significantly (P=.03) better image quality was observed for two-segment
      reconstruction only at heart rates of 80-82 beats per minute, at which temporal
      resolution was approximately 83 msec. For grading coronary artery stenosis,
      correlation was 0.64 for single- and 0.66 for two-segment reconstruction (P=.43).
      Significant stenosis (>50%) was detected on a per-segment basis with 77.1%
      sensitivity and 98.6% specificity by using single-segment and with 79.2%
      sensitivity and 99.1% specificity by using two-segment image reconstruction.
      CONCLUSION: At heart rates of more than 65 beats per minute, use of two-segment
      reconstruction improves image quality at multidetector CT coronary angiography
      but does not significantly affect overall diagnostic accuracy compared with
      single-segment reconstruction.

PMID- 17495178
TI  - Prostate cancer: body-array versus endorectal coil MR imaging at 3 T--comparison
      of image quality, localization, and staging performance.
AB  - PURPOSE: To prospectively compare image quality and accuracy of prostate cancer
      localization and staging with body-array coil (BAC) versus endorectal coil (ERC)
      T2-weighted magnetic resonance (MR) imaging at 3 T, with histopathologic findings
      as the reference standard. MATERIALS AND METHODS: After institutional review
      board approval and written informed consent, 46 men underwent 3-T T2-weighted MR
      imaging with a BAC (voxel size, 0.43 x 0.43 x 4.00 mm) and an ERC (voxel size,
      0.26 x 0.26 x 2.50 mm) before radical prostatectomy. Four radiologists
      independently evaluated data sets obtained with the BAC and ERC separately. Ten
      image quality characteristics related to prostate cancer localization and staging
      were assigned scores. Prostate cancer presence was recorded with a five-point
      probability scale in each of 14 segments that included the whole prostate.
      Disease stage was classified as organ-confined or locally advanced with a five
      point probability scale. Whole-mount-section histopathologic examination was the
      reference standard. Areas under the receiver operating characteristic curve
      (AUCs) and diagnostic performance parameters were determined. A difference with a
      P value of less than .05 was considered significant. RESULTS: Forty-six patients
      (mean age, 61 years) were included for analysis. Significantly more motion
      artifacts were present with ERC imaging (P<.001). All other image quality
      characteristics improved significantly (P<.001) with ERC imaging. With ERC
      imaging, the AUC for localization of prostate cancer was significantly increased
      from 0.62 to 0.68 (P<.001). ERC imaging significantly increased the AUCs for
      staging, and sensitivity for detection of locally advanced disease by experienced
      readers was increased from 7% (one of 15) to a range of 73% (11 of 15) to 80% (12
      of 15) (P<.05), whereas a high specificity of 97% (30 of 31) to 100% (31 of 31)
      was maintained. Extracapsular extension as small as 0.5 mm at histopathologic
      examination could be accurately detected only with ERC imaging. CONCLUSION: Image
      quality and localization improved significantly with ERC imaging compared with
      BAC imaging. For experienced radiologists, the staging performance was
      significantly better with ERC imaging.

PMID- 17495179
TI  - Multipath curved planar reformation of the peripheral arterial tree in CT
      angiography.
AB  - The study was approved by the institutional review board, and informed consent
      was obtained. The purpose of the study was to prospectively quantify the angular
      visibility range, determine the existence of orthogonal viewing pairs, and
      characterize the conditions that cause artifacts in multipath curved planar
      reformations (MPCPRs) of the peripheral arterial tree in 10 patients (eight men
      and two women; mean age, 69 years; range, 54-80 years) with peripheral arterial
      occlusive disease. Percentage of segments with the maximal possible visibility
      score of 1 was significantly greater (odds ratio, 1.42; P<.001) for MPCPRs than
      for maximum intensity projections. One or more orthogonal viewing pairs were
      identified for all above-knee arterial segments, and artifactual vessel
      distortion was observed when the vessel axis approached a horizontal course in
      MPCPRs.

PMID- 17495180
TI  - Waist Circumference and Cardiometabolic Risk: a Consensus Statement from Shaping
      America's Health: Association for Weight Management and Obesity Prevention;
      NAASO, the Obesity Society; the American Society for Nutrition; and the American
      Diabetes Association.

PMID- 17495181
TI  - Peroxisome proliferator-activated receptor gamma 2 and acyl-CoA synthetase 5
      polymorphisms influence diet response.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) and its response
      gene, Acyl CoA synthetase 5 (ACSL5), which has an important role in fatty acid
      metabolism, may affect weight loss in response to caloric restriction. Therefore,
      we aimed to determine whether these genes were involved in the interindividual
      response to dietary treatment. Genotypic/phenotypic comparisons were made between
      selected obese women from the quintiles losing the most (diet responsive, n = 74)
      and the quintiles losing the least (diet-resistant, n = 67) weight in the first 6
      weeks of a 900-kcal formula diet. Two common PPARgamma single nucleotide
      polymorphisms, Pro(12)Ala and C1431T, and eight polymorphisms across the ACSL5
      gene were selected for single locus and haplotypic association analyses. The
      PPARgamma Pro(12)Ala single nucleotide polymorphism was associated with diet
      resistance (odds ratio = 3.48, 95% confidence interval = 1.41 to 8.56, p = 0.03),
      and the rs2419621, located in the 5'untranslated region of the ACSL5 gene,
      displayed the strongest association with diet response (odds ratio = 3.45, 95%
      confidence interval = 1.61 to 7.69, p = 0.001). Skeletal muscle ACSL5 mRNA
      expression was significantly lower in carriers of the wildtype compared with the
      variant rs2419621 allele (p = 0.03). Our results suggest a link between
      PPARgamma2 and ACSL5 genotype and diet responsiveness.

PMID- 17495182
TI  - Heterogeneous effect of peroxisome proliferator-activated receptor gamma2 Ala12
      variant on type 2 diabetes risk.
AB  - Conflicting results have been reported regarding whether the PPARgamma2 Pro12Ala
      polymorphism plays a role in the risk of type 2 diabetes (T2D), suggesting
      genetic heterogeneity. To investigate this issue, a meta-analysis of 41 published
      and 2 unpublished studies (a total of 42,910 subjects) was conducted. Ala12
      carriers had a 19% T2D risk reduction, but this association was highly
      heterogeneous (p = 0.005). A great proportion (48%) of heterogeneity was
      explained by the controls' BMI, with risk reduction being greater when BMI was
      lower. Risk reduction of Ala12 carriers in Asia (35%) was higher than in Europe
      (15%, p = 0.02) and tended to be higher than in North America (18%, p = 0.10).
      Difference between Asians and Europeans was no longer significant (p = 0.15)
      after adjusting for the controls' BMI. Studies from Europe were still
      heterogeneous (p = 0.02) with risk reduction in Ala12 carriers being
      progressively smaller (test for trend in the odds ratios, p = 0.02) from Northern
      (26% reduction, p < 0.0001) to Central (10%, p = 0.04) and Southern (0%, p =
      0.94) Europe. In conclusion, in our meta-analysis, the reduced risk of T2D in
      Ala12 carriers is not homogeneous. It is greater in Asia than in Europe and,
      among Europeans, it is higher in Northern Europe, barely significant in Central
      Europe, and nonexistent in Southern Europe.

PMID- 17495183
TI  - Tenomodulin is associated with obesity and diabetes risk: the Finnish diabetes
      prevention study.
AB  - We recently showed that long-term weight reduction changes the gene expression
      profile of adipose tissue in overweight individuals with impaired glucose
      tolerance (IGT). One of the responding genes was X-chromosomal tenomodulin
      (TNMD), a putative angiogenesis inhibitor. Our aim was to study the associations
      of individual single nucleotide polymorphisms and haplotypes with adiposity,
      glucose metabolism, and the risk of type 2 diabetes (T2D). Seven single
      nucleotide polymorphisms from two different haploblocks were genotyped from 507
      participants of the Finnish Diabetes Prevention Study (DPS). Sex-specific
      genotype effects were observed. Three markers of haploblock 1 were associated
      with features of adiposity in women (rs5966709, rs4828037) and men (rs11798018).
      Markers rs2073163 and rs1155794 from haploblock 2 were associated with 2-hour
      plasma glucose levels in men during the 3-year follow-up. The same two markers
      together with rs2073162 associated with the conversion of IGT to T2D in men. The
      risk of developing T2D was approximately 2-fold in individuals with genotypes
      associated with higher 2-hour plasma glucose levels; the hazard ratios were 2.192
      (p = 0.025) for rs2073162-A, 2.191 (p = 0.027) for rs2073163-C, and 1.998 (p =
      0.054) for rs1155974-T. These results suggest that TNMD polymorphisms are
      associated with adiposity and also with glucose metabolism and conversion from
      IGT to T2D in men.

PMID- 17495184
TI  - Trends in the prevalence of overweight and obesity among young Australians, 1985,
      1997, and 2004.
AB  - OBJECTIVE: To determine secular trends in overweight/obesity among 7- to 15-year
      olds for the periods 1985, 1997, and 2004. RESEARCH METHOD AND PROCEDURES: Data
      from representative surveys conducted in New South Wales, Australia, in 1985,
      1997, and 2004 were analyzed. Height and weight were measured, and BMI categories
      were created using International Obesity Task Force definitions. Students were
      grouped as Grades 2 + 4 + 6 and 8 + 10. RESULTS: The prevalences of
      overweight/obesity for 1985, 1997, and 2004 were 10.9%, 20.6%, and 25.7% among
      the younger boys and 10.6%, 19.5%, and 26.1% among the older boys. The average
      annual rate of increase for 1985 to 1997 was 0.81% and for 1997 to 2004 was 0.73%
      among the younger boys and was 0.74% and 0.94% for the two periods among the
      older boys. The prevalences of overweight/obesity in 1985, 1997, and 2004 were
      14.0%, 22.0%, and 24.8% among the younger girls and 8.3%, 17.9%, and 19.8% among
      the older girls, respectively. The average annual rates of increase for the two
      periods were 0.8% and 0.4% among the younger girls and 0.80% and 0.27% among the
      older girls. Change in the prevalence of overweight/obesity and socioeconomic
      status were not associated. DISCUSSION: Over the period 1985 to 1997, the
      prevalence of overweight and obesity increased significantly among the younger
      and older boys and the younger girls. The prevalence of overweight, but not
      obesity, increased among the older girls over this period. Over the period 1997
      to 2004, the prevalence of overweight/obesity combined increased significantly
      among boys of both age groups but not among girls.

PMID- 17495185
TI  - Probable blind spot in the International Diabetes Federation definition of
      metabolic syndrome.
AB  - OBJECTIVES: The International Diabetes Federation (IDF) proposed a novel
      definition of the metabolic syndrome (MS) in 2005, which designated central
      obesity as mandatory. The new National Cholesterol Education Program (NCEP)
      version, announced by the American Heart Association and National Heart Lung and
      Blood Institute in October 2005, did not favor any of the five components. We set
      out to compare the cardiovascular profiles of patients cross-defined by these two
      definitions to shed light on the differential meanings of the two. RESEARCH
      METHODS AND PROCEDURES: We analyzed data from 2608 non-institutionalized adults
      (> or =19 years old) in the National Nutrition and Health Survey in Taiwan, who
      had complete data for the five MS defining components. Both definitions adopted
      lower cut-points for fasting glucose and race-specific cut-points for waist
      circumference. RESULTS: Under the IDF's and new NCEP's definitions, the MS
      prevalence was 6.2% and 11.6% in men and 12.6% and 16.5% in women, respectively.
      Although the two definitions had high agreement, IDF failed to pick up
      approximately 4% to 5% of people with more than three MS component disorders but
      a waist circumference less than the cut-point. Subjects whose physical conditions
      only satisfied NCEP's definition had similar or worse metabolic profiles than
      those whose conditions satisfied both IDF's definition and the new NCEP's
      definition. DISCUSSION: The IDF definition would fail to identify a portion of
      people who have more than three MS component disorders but a small waistline.
      Further research and discussion are needed on whether and how to implement the
      IDF's definition.

PMID- 17495186
TI  - Self-identities and BMI of Minnesotan soy consumers and non-consumers.
AB  - OBJECTIVE: The purpose of this study was to identify self-identities among
      mainstream and natural foods shoppers and the relationship of these self
      identities to soy consumption and BMI. We hypothesized that soy consumers (SCs)
      would have lower BMIs than non-consumers (NCs) and that persons who self-identify
      themselves as SCs, natural foods, organic foods, health conscious, whole foods
      consumers, and vegetarians would have higher intakes of soy. RESEARCH METHODS AND
      PROCEDURES: A validated soy foods frequency questionnaire was administered to 298
      adult mainstream and natural foods grocery store shoppers in Minneapolis/St.
      Paul, MN. An additional survey gathered information on consumers' self
      identification with several dietary and lifestyle descriptors. Principal
      component analysis was used to extract factors representing overarching self
      identities. Correlation coefficients between derived scales for each factor and
      BMI and soy servings per week were generated using a Spearman correlation. One
      way ANOVA was used to test significance between derived scales for factors and
      demographic variables and store type. Multiple regression models were used to
      test association between derived scales and BMI and soy servings per week while
      adjusting for demographic covariates. RESULTS: Asians and those who shopped at
      natural food grocery stores consumed more soy foods and had lower BMIs than other
      ethnicities or those who shopped at mainstream grocery stores. Five overarching
      self-identities were found: vegetarian, mainstream, nouveau gourmet, pleasure,
      and bargain. Vegetarian and nouveau gourmet self-identities consumed
      significantly greater amounts of soy foods and had significantly lower BMIs,
      whereas mainstream self-identities consumed significantly less soy foods and had
      significantly higher BMIs. DISCUSSION: Self-identities influence soy food
      consumption and BMI.

PMID- 17495187
TI  - Transcriptomic characterization of the long-term dihydrotestosterone effects in
      adipose tissue.
AB  - OBJECTIVE: To study the long-term transcriptomic effects of dihydrotestosterone
      (DHT) in adipose tissue. Fat distribution is regulated by sexual hormones. It is
      still unclear if androgens are promoting or reducing intra-abdominal fat
      accumulation. RESEARCH METHODS AND PROCEDURES: Retroperitoneal adipose tissue
      were isolated from each group of gonadectomized (GDX) C57BL6 male mice treated
      with vehicle or DHT for 21 days. Serial analysis of gene expression (SAGE) was
      performed to generate approximately 150,000 SAGE tags from each sample. RESULTS:
      Among the numerous genes regulated by DHT, transcripts involved in glycolysis,
      such as aldolase 1 A isoform and pyruvate kinase muscle as well as lipogenic
      transcripts, such as malic enzyme supernatant and ELOVL family member 6
      elongation of long chain fatty acids were down-regulated by androgen
      supplementation. In contrast, transcripts involved in lipolysis and fatty acid
      oxidation, such as carboxylesterase 3, acetyl-coenzyme A acyltransferase 1, 3
      ketoacyl-CoA thiolase B and enoyl-coenzyme A hydratase/3-hydroxyacyl coenzyme A
      dehydrogenase were up-regulated by DHT. Pro-apoptotic transcripts such as cell
      death-inducing DFFA-like effector c, BCL2/adenovirus E1B 19 kDa-interacting
      protein 1 NIP3 and -interacting protein 3-like were up-regulated by DHT, whereas
      transcripts involved in promotion of cell cycle such as cyclin D2 were down
      regulated by DHT. DISCUSSION: These results suggest that chronic androgen
      treatment may help to improve metabolic profile by regulating various critical
      pathways involved in adipose tissue physiology. In addition, several genes
      associated with a healthier metabolic profile, such as adiponectin and CD36
      antigen, were up-regulated by 21 days of DHT treatment.

PMID- 17495188
TI  - Potential of intestinal electrical stimulation for obesity: a preliminary canine
      study.
AB  - OBJECTIVE: The aims of this study were to investigate the therapeutic potential
      of intestinal electrical stimulation (IES) for obesity. Experiments were
      performed to investigate the effects of IES on food intake, gastric tone, gastric
      accommodation, and its possible pathway. RESEARCH METHODS AND PROCEDURES: Ten
      normal dogs and six dogs with truncal vagotomy were used in this study. Each dog
      was equipped with a gastric cannula for the measurement of gastric tone and
      accommodation by barostat and one pair of duodenal serosal electrodes for IES.
      The experiment on food intake was composed of both control session without IES
      and IES session after a 28-hour fast. The experiment on gastric tone and
      accommodation was performed in the fasting and fed states and composed of three
      sessions: control, IES, and IES with N(G)-nitro-l-arginine. RESULTS: IES
      significantly reduced food intake in the normal dogs (459.0 vs. 312.6 grams, p <
      0.001). The food intake was negatively correlated with the fasting gastric volume
      during IES. IES significantly decreased fasting gastric tone in the normal dogs
      reflected as a decrease in gastric volume (89.1 vs. 261.3 mL, p < 0.01), which
      was abolished by vagotomy and N(G)-nitro-l-arginine. DISCUSSION: IES reduces food
      intake and inhibits gastric tone in the fasting state. The inhibitory effect of
      IES on gastric tone is mediated by both vagal and nitrergic pathway.

PMID- 17495189
TI  - Intake of dietary magnesium and the prevalence of the metabolic syndrome among
      U.S. adults.
AB  - OBJECTIVE: Limited data suggest that people with the metabolic syndrome have
      lower intakes or circulating concentrations of magnesium than those who do not
      have the syndrome. The aim of this study was to examine the associations between
      dietary intake of magnesium and the prevalence of the metabolic syndrome in a
      nationally representative sample of U.S. adults. RESEARCH METHODS AND PROCEDURES:
      We used data for 7669 participants > or =20 years of age of the Third National
      Health and Nutrition Examination Survey (1988 to 1994). The metabolic syndrome
      was defined using the criteria of the National Cholesterol Education Program.
      Magnesium intake was determined from a single dietary 24-hour recall. RESULTS:
      The unadjusted prevalences of the metabolic syndrome were 29.0% (quintile of
      lowest magnesium intake), 27.5%, 25.8%, 23.9%, and 21.8% for increasing quintiles
      of magnesium intake (p for trend = 0.002). After multiple adjustment, the odds
      ratios for the second through the fifth quintiles (highest intake) of magnesium
      intake among all participants included in the analysis were 0.84 [95% confidence
      interval (CI): 0.58, 1.23], 0.76 (95% CI: 0.54, 1.07), 0.62 (95% CI: 0.40, 0.98),
      and 0.56 (95% CI: 0.34, 0.92), respectively (p for trend = 0.029). The
      associations were similar for men and women. DISCUSSION: Our results showing an
      inverse association between dietary magnesium intake and the prevalence of the
      metabolic syndrome add to the evidence that adequate magnesium intake or a diet
      rich in magnesium may be important for maintaining good cardiometabolic health.

PMID- 17495190
TI  - Dehydroepiandrosterone sulfate and high-density lipoprotein-cholesterol levels in
      overweight children.
AB  - OBJECTIVE: The association of childhood overweight with cardiovascular risk
      factors seems to change by sex and age, which may indicate that hormonal status
      could be the cause of this different association. In this study, we analyzed the
      relationship of dehydroepiandrosterone sulfate (DHEA-S) with the alterations
      associated with overweight by analyzing the influence of this hormone in the
      differences found in biochemical variables between normal-weight and overweight
      prepubertal children. RESEARCH METHODS AND DESIGN: The study included 684 6- to 8
      year-old children (350 boys and 334 girls) categorized by the presence or absence
      of overweight, according to the age- and sex-specific cut-off points proposed for
      children. Lipid levels were determined by standard methods. DHEA-S and insulin
      levels were measured by radioimmunoassay. Biochemical variables were compared
      between normal-weight and overweight children by tertiles of DHEA-S. RESULTS: We
      observed that plasma high-density lipoprotein-cholesterol (HDL-C) and
      apolipoprotein (apo)-AI levels were significantly lower in overweight than in
      normal-weight boys only in the highest tertile of DHEA-S. No significant
      differences in plasma glucose levels, total cholesterol, low-density lipoprotein
      cholesterol, or apo B were found between overweight and normal-weight children in
      any DHEA-S tertile. In a Spearman correlation analysis, we observed a significant
      and negative correlation for weight and BMI with HDL-C and for weight and apo-AI
      levels only in the highest tertile of DHEA-S. DISCUSSION: Our study showed that,
      in our prepubertal population, the association of overweight with decreased HDL-C
      and apo-AI levels was present only in boys within the highest levels of DHEA-S,
      supporting the importance of hormonal influences on the association of metabolic
      alterations with overweight.

PMID- 17495191
TI  - Omental 11beta-hydroxysteroid dehydrogenase 1 correlates with fat cell size
      independently of obesity.
AB  - OBJECTIVES: In ideopathic obesity, there is evidence that enhanced cortisol
      regeneration within abdominal subcutaneous adipose tissue may contribute to
      adiposity and metabolic disease. Whether the cortisol regenerating enzyme, 11beta
      hydroxysteroid dehydrogenase type 1 (11betaHSD1), or glucocorticoid receptor
      (GRalpha) levels are altered in other adipose depots remains uncertain. Our
      objective was to determine the association between 11betaHSD1 and GRalpha mRNA
      levels in four distinct adipose depots and measures of obesity and the metabolic
      syndrome. RESEARCH METHODS AND PROCEDURES: Adipose tissue biopsies were collected
      from subcutaneous (abdominal, thigh, gluteal) and intra-abdominal (omental)
      adipose depots from 21 women. 11betaHSD1 and GRalpha mRNA levels were measured by
      real-time polymerase chain reaction. Body composition, fat distribution, fat cell
      size, and blood lipid, glucose, and insulin levels were measured. RESULTS:
      11betaHSD1 mRNA was highest in abdominal subcutaneous (p < 0.001) and omental (p
      < 0.001) depots and was positively correlated with BMI and visceral adiposity in
      all depots. Omental 11betaHSD1 correlated with percent body fat (R = 0.462, p <
      0.05), fat cell size (R = 0.72, p < 0.001), and plasma triglycerides (R = 0.46, p
      < 0.05). Conversely, GRalpha mRNA was highest in omental fat (p < 0.001). GRalpha
      mRNA was negatively correlated with BMI in the abdominal subcutaneous (R = 
      0.589, p < 0.05) and omental depots (R = -0.627, p < 0.05). Omental GRalpha mRNA
      was inversely associated with visceral adiposity (R = -0.507, p < 0.05), fat cell
      size (R = -0.52, p < 0.01), and triglycerides (R = -0.50, p < 0.05). DISCUSSION:
      Obesity was associated with elevated 11betaHSD1 mRNA in all adipose compartments.
      GRalpha mRNA is reduced in the omental depot with obesity. The novel correlation
      of 11betaHSD1 with omental fat cell size, independent of obesity, suggests that
      intracellular cortisol regeneration is a strong predictor of hypertrophy in the
      omentum.

PMID- 17495192
TI  - Relationships of cardiac autonomic function with metabolic abnormalities in
      childhood obesity.
AB  - OBJECTIVE: The objective was to examine cardiovascular autonomic (cANS) function
      and its potential relationships with leptin resistance, insulin resistance,
      oxidative stress, and inflammation in a pediatric sample with varying levels of
      obesity. RESEARCH METHODS AND PROCEDURES: Participants were normal-weight (NW;
      BMI <85th percentile, 6 male, 4 female), overweight (OW; 85th percentile < BMI
      <95th percentile, 6 male, 4 female), and obese children (OB; BMI >95th
      percentile, 6 male, 10 female) who had cANS function assessed via heart rate
      variability (HRV) methods during resting conditions. Standard time-domain and
      frequency-domain measures [high-frequency normalized units (HFnu; measure of
      parasympathetic nervous system activity) and low frequency:high-frequency ratio
      (LF:HF; overall sympathovagal balance)] of HRV were calculated. Fasting blood
      samples were drawn for measurement of glucose, insulin, lipids, 8-isoprostane,
      leptin, soluble leptin-receptor (sOB-R), C-reactive protein (CRP), interleukin-6
      (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Results were reported as
      mean +/- standard error of the mean. RESULTS: OB had significantly elevated LF:HF
      and decreased HFnu when compared with NW (p < 0.05), but no differences between
      OW and NW were observed. Measures of HRV were significantly related to leptin,
      insulin resistance, 8-isoprostane, and CRP (p < 0.05), but these relationships
      were not significant after adjustment for fat mass. DISCUSSION: When compared
      with NW, OB but not OW children are characterized by cANS dysfunction and
      increased leptin, insulin resistance, oxidative stress, and inflammation (CRP).
      The relationships between these factors seem to be dependent on quantity of fat
      mass and/or other factors associated with being obese.

PMID- 17495193
TI  - Effects of pronounced weight loss on adiponectin oligomer composition and
      metabolic parameters.
AB  - OBJECTIVE: Adiponectin is an adipocytokine secreted into circulation in three
      isoforms. The aim of the study was to investigate changes of adiponectin isoforms
      during profound weight loss and its relation to anthropomorphometric and
      metabolic parameters. RESEARCH METHODS AND PROCEDURES: Thirteen severely obese
      female subjects were examined before and 1 year after surgical treatment. Total
      adiponectin was determined by radioimmunosorbent assay, and oligomer composition
      was detected by nondenaturing Western blot. RESULTS: BMI decreased substantially
      (p < 0.001), which was associated with an increase of total adiponectin from 12.9
      +/- 5.9 to 14.3 +/- 6.1 microg/mL (p = 0.055). Medium molecular weight (MMW)
      adiponectin increased from 7.5 +/- 3.6 to 9.1 +/- 4.1 microg/mL (p = 0.009),
      whereas high (HMW) and low molecular weight adiponectin remained unchanged. Delta
      values of total adiponectin correlated significantly with Delta values of
      anthropometric parameters. Similar correlations were found for Delta values of
      MMW (Delta weight: r(2) = 0.4132, p = 0.0178; Delta BMI: r(2) = 0.3319, p =
      0.0393; Delta fat mass: r(2) = 0.5202, p = 0.0054). DISCUSSION: Thus, profound
      weight loss was associated with an increase in total adiponectin, which was
      mainly and consistently caused by increases in MMW adiponectin (p = 0.009). These
      changes result in a shift from low molecular weight to MMW and HMW adiponectin
      isoforms, which may be related to improvements in both anthropometric and
      metabolic parameters.

PMID- 17495194
TI  - Low-dose pramlintide reduced food intake and meal duration in healthy, normal
      weight subjects.
AB  - OBJECTIVE: We previously reported that a single preprandial injection (120
      microg) of pramlintide, an analog of the beta-cell hormone amylin, reduced ad
      libitum food intake in obese subjects. To further characterize the meal-related
      effects of amylin signaling in humans, we studied a lower pramlintide dose (30
      microg) in normal-weight subjects. RESEARCH METHODS AND PROCEDURES: In a
      randomized, double-blind, placebo-controlled, cross-over study, 15 healthy men
      (age, 24 +/- 7 years; BMI, 22.2 +/- 1.8 kg/m(2)) underwent a standardized buffet
      meal test on two occasions. After an overnight fast, subjects received a single
      subcutaneous injection of pramlintide (30 microg) or placebo, followed
      immediately by a standardized pre-load meal. After 1 hour, subjects were offered
      an ad libitum buffet meal, and total caloric intake and meal duration were
      measured. RESULTS: Compared with placebo, pramlintide reduced total caloric
      intake (1411 +/- 94 vs. 1190 +/- 117 kcal; Delta, -221 +/- 101 kcal; -14 +/- 9%;
      p = 0.05) and meal duration (36 +/- 2 vs. 31 +/- 3 minutes; Delta, -5.1 +/- 1.4
      minutes; p < 0.005). Visual analog scale profiles of hunger trended lower and
      fullness higher during the first hour after pramlintide administration. In
      response to the buffet, hunger and fullness changed to a similar degree after
      pramlintide and placebo, despite subjects on pramlintide consuming 14% fewer
      kilocalories. Visual analog scale nausea ratings remained near baseline, without
      differences between treatments. Plasma peptide YY, cholecystokinin, and ghrelin
      concentrations did not differ with treatment, whereas glucagon-like peptide-1
      concentrations after meals were lower in response to pramlintide than to placebo.
      DISCUSSION: These observations add support to the concept that amylin agonism may
      have a role in human appetite control.

PMID- 17495195
TI  - Changes in body composition with weight loss: obese subjects randomized to
      surgical and medical programs.
AB  - OBJECTIVE: To assess changes in body composition with weight loss in obese
      subjects randomized to a laparoscopic adjustable gastric band surgical program or
      a medical program using a very-low-energy diet and orlistat. RESEARCH METHODS AND
      PROCEDURES: Using body composition measurements by DXA, neutron activation for
      total body nitrogen, and whole body gamma counting for total body potassium, we
      studied changes in fat mass, fat distribution, fat-free mass, total bone mineral
      content, total body protein, and body cell mass at 6 (n = 61 paired) and 24
      months (n = 53 paired) after randomization. RESULTS: At 24 months, the surgical
      group had lost significantly more weight (surgical, 20.3 +/- 6.5 kg; medical, 5.9
      +/- 8.0 kg). There was favorable fat-free mass to fat mass loss ratios for both
      groups (surgical, 1:5.5; medical, 1:5.9). Changes in total body nitrogen or
      potassium were favorable in each group. A small reduction in mean bone mineral
      content occurred throughout the study but was not associated with extent of
      weight loss or treatment group. At 6 months, weight loss for both groups was
      similar (surgical, 14.1 +/- 4.5 kg; medical, 13.3 +/- 7.3 kg). The medical
      program subjects lost less fat-free mass and skeletal muscle and had increased
      total body protein. The proportion of body fat to limb fat remained remarkably
      constant throughout the study. DISCUSSION: Weight loss programs used in this
      study induced fat loss without significant deleterious effects on the components
      of fat-free mass.

PMID- 17495196
TI  - Body mass, DRD4, physical activity, sedentary behavior, and family socioeconomic
      status: the add health study.
AB  - OBJECTIVE: To investigate the joint role of the 48-base pair repeat polymorphism
      of the dopamine receptor 4 gene (DRD4) and environmental factors in body mass
      variation among an ethnically diverse sample of U.S. adolescents and young
      adults. RESEARCH METHODS AND PROCEDURES: Approximately 2600 adolescent and young
      adults in the National Longitudinal Study of Adolescent Health (Add Health) who
      provided DNA measures and measures of height and weight were included in the
      analysis. Mixed regression modeling was used to investigate the effects of the
      7R/7R and any5R variants in the DRD4 gene simultaneously with the effects of
      physical activity (PA), sedentary behavior (SB), and family socioeconomic status
      (SES) on body mass variation. European Americans, African Americans, and Hispanic
      Americans were modeled separately. RESULTS AND DISCUSSION: Both the 7R/7R and
      any5R genotypes of the DRD4 gene were associated with age- and sex-specific BMI
      percentile score (BMI-P) based on the Centers for Disease Control and
      Prevention/National Center for Health Statistics 2000 reference curves among
      African Americans and only among African Americans (N = 413) 20 years old or
      younger. Neither genetic variants are associated with the BMI measure among white
      (N = 1386) and Hispanic-American (N = 331) adolescents. The presence of the 7R/7R
      genotype was associated with a reduction of 15.1 in BMI percentile (p = 0.005),
      and the presence of any5R was associated with an increase of 15.5 in BMI
      percentile (p = 0.003), after adjusting for PA, SB, and family SES. Neither PA
      nor SB as measured in Add Health is importantly associated with BMI-P, suggesting
      a complex relationship between body mass and PA/SB among adolescents and young
      adults. Family SES is negatively related to BMI-P in the European-American
      sample.

PMID- 17495197
TI  - A genome-wide scan of loci linked to serum adiponectin in two populations of
      African descent.
AB  - OBJECTIVE: The objectives were to identify quantitative trait loci linked to
      serum adiponectin concentration and to estimate heritability in two populations
      of African descent. RESEARCH METHODS AND PROCEDURES: We conducted a genome scan
      for serum adiponectin concentration in two populations of African descent. Genome
      wide microsatelitte markers were typed in an African-American population
      consisting of 203 families from the Chicago area and in a Nigerian Yoruba
      population consisting of 146 families. Linkage analysis was performed to identify
      loci. Variance component model was used to estimate heritability. RESULTS:
      Estimates of heritability adjusted for age, gender, and BMI were 0.45 and 0.70
      for the African-American and Nigerian families, respectively. In both
      populations, adiponectin was significantly negatively correlated with BMI,
      height, and weight. After adjusting for age, gender, and BMI, we found evidence
      of genetic linkage to adiponectin on chromosomes 11 [limit of detection (LOD)
      score = 2.89] and 17 (LOD score = 1.35) in the Nigerian sample. Among the African
      Americans, we found genetic linkage on chromosomes 2 (LOD score = 1.82), 4 (LOD
      score = 2.12), and 11 (LOD score = 2.33). Analysis based on combined data yielded
      a maximum LOD score of 3.21 on chromosome 11. DISCUSSION: Consistency of the
      finding on chromosome 11 suggests that this region is likely to be involved in
      regulation of adiponectin, either through a primary influence on hormone levels
      or through pathways influencing body composition. These results suggest that
      adiponectin could be a potential therapeutic target for obesity.

PMID- 17495198
TI  - Effects of acute and chronic protein intake on metabolism, appetite, and ghrelin
      during weight loss.
AB  - OBJECTIVE: This study evaluated the effects of acute and chronic consumption of
      higher dietary protein on energy expenditure, macronutrient use, appetite, and
      appetite-regulating hormones during weight loss in women. RESEARCH METHODS AND
      PROCEDURES: Thirty-eight women chronically consuming a 750 kcal/d energy-deficit
      diet with a protein content of 30% (higher protein-chronic diet, HP-CD, n = 21)
      or 18% (normal protein-chronic diet, NP-CD, n = 17) for 9 weeks were tested. On
      separate days, metabolic, appetite, and hormonal responses were measured over 4
      hours when the women consumed a higher protein-acute meal (HP-AM) (30% of energy
      as protein) or a normal protein-acute meal (NP-AM) (18% of energy as protein).
      RESULTS: With chronic diet groups combined, HP-AM led to lower respiratory
      exchange ratio (0.829 +/- 0.005 vs. 0.843 +/- 0.008; p < 0.05), lower
      carbohydrate oxidation (p < 0.05), and higher fat oxidation (p < 0.05) compared
      with NP-AM. HP-AM also led to reduced self-reported postprandial hunger (p <
      0.001) and desire to eat (p < 0.001) and lower postprandial ghrelin (252 +/- 16
      vs. 274 +/- 18 ng/mL x 240 minutes, p < 0.05) compared with NP-AM. No differences
      in postprandial energy expenditure (PPEE) occurred between meals. When combining
      acute meals, respiratory exchange ratio was lower (p < 0.05) and protein
      oxidation (p < 0.001) was higher in the HP-CD vs. NP-CD. An acute meal-by-chronic
      diet interaction was observed with PPEE such that HP-AM led to greater PPEE in
      the HP-CD vs. NP-CD (28.7 +/- 2.7 vs. 19.9 +/- 2.7 kcal/min for 195 minutes; p <
      0.05). CONCLUSIONS: During weight loss, thermogenesis and protein use appear to
      be influenced by chronic protein intake, while appetite and ghrelin are more
      responsive to acute protein intake.

PMID- 17495199
TI  - Physical activity patterns during weight maintenance following a low-energy
      density dietary intervention.
AB  - OBJECTIVE: The objective was to determine the role of physical activity (PA) and
      energy intake on weight maintenance among former University of Alabama at
      Birmingham EatRight Weight Management Program participants. RESEARCH METHODS AND
      PROCEDURES: Eighty-nine former participants completed follow-up visits > or =1
      year after completing EatRight. BMI was calculated using measured height and
      weight. Diet intake was estimated from 4-day food records. PA was assessed using
      a module from the Behavioral Risk Factor Surveillance System Survey. Cut-off
      points were chosen based on the distribution of minutes of activity. For moderate
      and total activity, cut-off points were 0, 1 to 30, 31 to 60, and >60 minutes.
      For vigorous activity, the categories were 0, 1 to 20, 21 to 30, and >30 minutes.
      General linear models determined the association of PA with change in weight at
      follow-up controlling for gender and total energy intake (kcal/d). RESULTS: At
      follow-up, 80% (n = 71) of participants maintained (regained <5% of program end
      weight) their body weight and 20% had gained weight. Mean weight change was 1.0
      +/- 6.5 kg. Maintainers consumed 384 fewer kcal/d on average. Maintainers had a
      lower energy density dietary pattern (1.58 vs. 2.01 kcal/g, p < 0.01). There was
      no significant difference in PA min/d reported by maintainers and gainers.
      DISCUSSION: Our results suggest that, despite being minimally active, weight
      reduced individuals can successfully maintain their newly achieved body weight
      with appropriate caloric intake. Adopting a lower calorie, low energy density
      dietary pattern may reduce the amount of PA that is truly necessary for weight
      maintenance.

PMID- 17495200
TI  - Triaxial accelerometry for assessment of physical activity in young children.
AB  - OBJECTIVE: The purpose of the present study was to derive linear and non-linear
      regression equations that estimate energy expenditure (EE) from triaxial
      accelerometer counts that can be used to quantitate activity in young children.
      We are unaware of any data regarding the validity of triaxial accelerometry for
      assessment of physical activity intensity in this age group. RESEARCH METHODS AND
      PROCEDURES: EE for 27 girls and boys (6.0 +/- 0.3 years) was assessed for nine
      activities (lying down, watching a video while sitting and standing, line drawing
      for coloring-in, playing blocks, walking, stair climbing, ball toss, and running)
      using indirect calorimetry and was then estimated using a triaxial accelerometer
      (ActivTracer, GMS). RESULTS: Significant correlations were observed between
      synthetic (synthesized tri-axes as the vector), vertical, and horizontal
      accelerometer counts and EE for all activities (0.878 to 0.932 for EE). However,
      linear and non-linear regression equations underestimated EE by >30% for stair
      climbing (up and down) and performing a ball toss. Therefore, linear and non
      linear regression equations were calculated for all activities except these two
      activities, and then evaluated for all activities. Linear and non-linear
      regression equations using combined vertical and horizontal acceleration counts,
      synthetic counts, and horizontal counts demonstrated a better relationship
      between accelerometer counts and EE than did regression equations using vertical
      acceleration counts. Adjustment of the predicted value by the regression
      equations using the vertical/horizontal counts ratio improved the overestimation
      of EE for performing a ball toss. DISCUSSION: The results suggest that triaxial
      accelerometry is a good tool for assessing daily EE in young children.

PMID- 17495201
TI  - Dietary interaction of high fat and marginal copper deficiency on cardiac
      contractile function.
AB  - OBJECTIVE: High-fat and marginally copper-deficient diets impair heart function,
      leading to cardiac hypertrophy, increased lipid droplet volume, and compromised
      contractile function, resembling lipotoxic cardiac dysfunction. However, the
      combined effect of the two on cardiac function is unknown. This study was
      designed to examine the interaction between high-fat and marginally copper
      deficient diets on cardiomyocyte contractile function. RESEARCH METHODS AND
      PROCEDURES: Weanling male rats were fed diets incorporating a low- or high-fat
      diet (10% or 45% of kcal from fat, respectively) with adequate (6 mg/kg) or
      marginally deficient (1.5 mg/kg) copper content for 12 weeks. Contractile
      function was determined with an IonOptix system including peak shortening (PS),
      time-to-PS, time-to-90% relengthening, maximal velocity of
      shortening/relengthening, and intracellular Ca(2+) ([Ca(2+)](I)) rise and decay.
      RESULTS: Neither dietary treatment affected blood pressure or glucose levels,
      although the high-fat diet elicited obesity and glucose intolerance. Both diets
      depressed PS, maximal velocity of shortening/relengthening, and intracellular
      Ca(2+) ([Ca(2+)](I)) rise and prolonged time-to-90% relengthening and Ca(2+)
      decay without an additive effect between the two. Ca(2+) sensitivity, apoptosis,
      lipid peroxidation, nitrosative damage, tissue ceramide, and triglyceride levels
      were unaffected by either diet or in combination. Phospholamban (PLB) but not
      sarco(endo)plasmic reticulum Ca(2+)-ATPase was increased by both diets.
      Endothelial NO synthase was depressed with concurrent treatments. The electron
      transport chain was unaffected, although mitochondrial aconitase activity was
      inhibited by the high-fat diet. DISCUSSION: These data suggest that high-fat and
      marginally copper deficient diets impaired cardiomyocyte contractile function and
      [Ca(2+)](i) homeostasis, possibly through a similar mechanism, without obvious
      lipotoxicity, nitrosative damage, and apoptosis.

PMID- 17495202
TI  - Successful long-term weight maintenance: a 2-year follow-up.
AB  - OBJECTIVE: To find factors associated with successful weight maintenance (WM) in
      overweight and obese subjects after a very low-calorie diet (VLCD). RESEARCH
      METHODS AND PROCEDURES: Subjects (133) followed a VLCD (2.1 MJ/d) for 6 weeks in
      a free-living situation. Of these, 103 subjects (age, 49.6 +/- 9.7 years; BMI,
      30.9 +/- 3.8 kg/m(2)) completed the following 2-year WM period. Body weight (BW),
      body composition, leptin concentration, attitude toward eating, and physical
      activity were determined right before (t0) and after (t1) the VLCD, after 3
      months (t2), after 1 year (t3), after 1.5 years (t4), and after 2 years (t5).
      RESULTS: BW loss during VLCD was 7.2 +/- 3.1 kg. After 2 years, follow-up BW
      regain was 69.0 +/- 98.4%. After 2 years of WM, 13 subjects were successful (<10%
      BW regain), and 90 were unsuccessful (>10% BW regain). At baseline, these groups
      were significantly different in BMI (33.7 +/- 4.7 vs. 30.5 +/- 3.5 kg/m(2),
      respectively; p < 0.05) and fat mass (38.3 +/- 9.8 vs. 32.1 +/- 8.3 kg, p <
      0.05). Successful subjects increased their dietary restraint significantly more
      during the whole study period (dietary restraint score, -4.9 +/- 4.4 vs. -2.1 +/-
      3.8). Furthermore, %BW regain was associated with the amount of percentage body
      fat lost during VLCD, which indicates that the more fat lost, the better the WM,
      suggesting a fat free mass-sparing effect. DISCUSSION: Characteristics such as
      the ability to increase dietary restraint and maintain this high level of
      restraint, fat free mass sparing, and a relatively high baseline BMI and fat mass
      were associated with successful long-term WM (<10% regain after 2 years).

PMID- 17495203
TI  - Weight gain prevention among women.
AB  - OBJECTIVE: Women 25 to 45 years old are at risk for weight gain and future
      obesity. This trial was designed to evaluate the efficacy of two interventions
      relative to a control group in preventing weight gain among normal or overweight
      women and to identify demographic, behavioral, and psychosocial factors related
      to weight gain prevention. RESEARCH METHODS AND PROCEDURES: Healthy women (N =
      284), ages 25 to 44, with BMI < 30 were randomized to one of three intervention
      conditions: a clinic-based group, a correspondence course, or an information-only
      control. Intervention was provided over 2 years, with a follow-up at Year 3. BMI
      and factors related to eating and weight were assessed yearly. RESULTS: Over the
      3-year study period, 40% (n = 114) of the women remained at or below baseline
      body weight (+/-2 lbs), and 60% gained weight (>2 lbs). Intervention had no
      effect on weight over time. Independently of intervention, women who were older,
      not actively dieting to lose weight, and who reported less perceived hunger at
      baseline were more likely to be successful at weight maintenance. Weight
      maintenance also was associated with increasing dietary restraint (conscious
      thoughts and purposeful behaviors to control calorie intake) and decreasing
      dietary disinhibition (the tendency to lose control over eating) over time.
      DISCUSSION: This study raises concern about the feasibility and efficacy of
      weight gain prevention interventions because most women were interested in weight
      loss, rather than weight gain prevention, and the interventions had no effect on
      weight stability. Novel approaches to the prevention of weight gain are needed.

PMID- 17495204
TI  - Does excess pregnancy weight gain constitute a major risk for increasing long
      term BMI?
AB  - OBJECTIVE: The objective was to assess the relevance of the recommendations of
      the Institute of Medicine (IOM), regarding gestational weight gain (GWG) for long
      term BMI development. RESEARCH METHODS AND PROCEDURES: The Stockholm Pregnancy
      and Women's Nutrition is a follow-up study of 483 women who delivered children in
      1984 to 1985. ANOVA was used to examine the change in body weight before
      pregnancy, at 6 months, and 1 year postpartum and 15 years after childbirth.
      Multiple linear regression was used to assess the predictors of BMI at 15-year
      follow-up. RESULTS: The weight increase from baseline to 15-year follow-up was
      6.2 kg for IOM-insufficient, 6.7 kg for IOM-recommended, and 10.0 kg for IOM
      excessive weight gain (p < 0.01). ANOVA showed a main effect of time, group and
      group by time interaction. The weight of the women who had excessive GWG was
      significantly greater at each time-point of follow-up than the weight of those
      who gained within or below recommendations. GWG was related to BMI at 15-year
      follow-up even after accounting for several confounders. Women who gained
      excessive weight during pregnancy had an increase of 0.72 kg/m(2) in long-term
      BMI compared with women who gained within recommendations. DISCUSSION: The
      findings support the adequateness of IOM guidelines, not only for the pregnancy
      related health matters, but also for preventing long-term weight retention after
      delivery. Healthcare providers should give women appropriate advice for
      controlling GWG and motivate them to lose pregnancy-related weight during
      postpartum to prevent future overweight.

PMID- 17495205
TI  - Binge eating disorder and night eating syndrome in adults with type 2 diabetes.
AB  - OBJECTIVE: To determine the prevalence of binge eating disorder (BED) and night
      eating syndrome (NES) among applicants to the Look AHEAD (Action for Health in
      Diabetes) study. RESEARCH METHODS AND PROCEDURES: The Eating Disorders
      Examination-Questionnaire (EDE-Q) and the Night Eating Questionnaire (NEQ) were
      used to screen patients. Phone interviews were conducted using the EDE for those
      who reported at least eight episodes of objective binge eating in the past month
      and using the Night Eating Syndrome History and Interview for those who scored >
      or =25 on the NEQ. Recruitment at four sites (Birmingham, n = 200; Houston, n =
      259; Minneapolis, n = 182; and Philadelphia, n = 204) yielded 845 participants
      (58% women; mean age = 60.1 +/- 6.7 years; mean BMI = 36.2 +/- 6.3 kg/m(2)).
      RESULTS: Screening scores were met by 47 (5.6%) applicants on the EDE-Q and 71
      (8.4%) on the NEQ. Of the 85% (40/47) who completed the EDE interview, 12 were
      diagnosed with BED, representing 1.4% of the total sample. Of the 72% (51/71) who
      completed the Night Eating Syndrome History and Interview, 32 were diagnosed with
      NES, equal to 3.8% of the total sample. Three participants had both BED and NES.
      Participants with eating disorders were younger, heavier, and reported more
      eating pathology than those without eating disorders. DISCUSSION: Among obese
      adults with type 2 diabetes, NES was reported more frequently than BED, which, in
      turn, was less common than expected.

PMID- 17495206
TI  - Which obesity index best explains prevalence differences in type 2 diabetes
      mellitus?
AB  - OBJECTIVE: Obesity drives the diabetes epidemic. However, it is not known which
      obesity index best explains variations in type 2 diabetes mellitus prevalence
      across populations. RESEARCH METHODS AND PROCEDURES: We analyzed three cross
      sectional studies from San Antonio, TX, (Mexican-Americans and non-Hispanic
      whites, n = 2839), Mexico City (n = 2233), and Spain (n = 2161) (age range, 35 to
      64 years). We used the area under the receiver operating characteristic curve
      (AUC) to assess performance for identifying diabetic subjects and logistic
      regression analysis to examine differences in diabetes prevalence. RESULTS: AUCs
      for waist circumference and BMI were similar in white subjects, but the AUC for
      waist circumference was greater in Mexican-origin subjects (Mexican men, 0.594
      vs. 0.549, p = 0.008; and women, 0.605 vs. 0.557, p = 0.002; Mexican-American
      men, 0.648 vs. 0.600, p < 0.001; and women, 0.744 vs. 0.693, p < 0.001). The AUC
      for waist-to-height ratio tended to be greater than that for waist circumference,
      but statistical significance was demonstrated only in Mexican women (0.628 vs.
      0.613, p = 0.044), Mexican-American women (0.774 vs. 0.758, p < 0.001), and
      Spanish women (0.734 vs. 0.715, p = 0.039). No obesity index was consistently
      superior to the others for explaining differences in diabetes prevalence among
      populations. CONCLUSIONS: In white and Mexican-origin men, waist circumference
      may be the preferred marker for identifying diabetic subjects on account of its
      simplicity; in women, waist-to-height ratio may be better. Differences in
      diabetes prevalence among these populations cannot be attributed to a single
      measure of obesity.

PMID- 17495207
TI  - Calcium and body fat in peripubertal girls: cross-sectional and longitudinal
      observations.
AB  - OBJECTIVE: The objective was to investigate whether calcium intake is
      independently associated with body fat in peripubertal girls. RESEARCH METHODS
      AND PROCEDURES: A total of 45 healthy premenarcheal girls (initially 10.5 +/- 0.6
      years of age) completed a 2-year prospective observational study. Percent body
      fat and trunk fat (by DXA), height, weight, maturational stage, and eating
      attitudes (children's Eating Attitudes Test [EAT]) were measured at baseline and
      at 1 and 2 years. Physical activity (by questionnaire) and calcium intake (by
      calcium-specific food frequency questionnaire and 3-day food records) were
      assessed at 6-month intervals. RESULTS: Girls with 2-year mean calcium intake
      below and above the median had similar age, height, lean mass, and maturational
      stage at baseline, but girls below the median had significantly higher baseline
      percentage body fat (29.3 +/- 10.3% vs. 22.0 +/- 6.8%, p < 0.01) and trunk fat
      (24.2 +/- 10.6% vs. 15.8 +/- 6.8%, p < 0.01). However, differences were no longer
      significant when covariates (most notably children's EAT dieting score) were
      considered. Regression analysis revealed that dieting score was a consistent
      positive predictor of percentage body and trunk fat at all cross-sectional time
      points, accounting for >20% of the variance, but did not predict 2-year change in
      percentage fat. Calcium intake did not enter longitudinal regression equations
      for 2-year change in percentage fat. DISCUSSION: In this group of girls, an
      inverse cross-sectional association between calcium intake and body fat appeared
      to result from avoidance of foods high in calcium by girls who were concerned
      about their body weight or shape. Calcium intake was not associated with change
      in fat over time.

PMID- 17495208
TI  - Association of cigarettes smoked daily with obesity in a general adult
      population.
AB  - OBJECTIVE: We analyzed the cross-sectional association between obesity and
      smoking habits, taking into account diet, physical activity, and educational
      level. RESEARCH METHODS AND PROCEDURES: We used data from the 2002 Swiss Health
      Survey, a population-based cross-sectional telephone survey assessing health and
      self-reported health behaviors. Reported smoking habits, height, and weight were
      available for 17,562 subjects (7844 men and 9718 women) > or =25 years of age.
      BMI was calculated as (self-reported) weight divided by height(2). RESULTS: Mean
      BMI was 25.1 kg/m(2) for non-smokers, 26.1 kg/m(2) for ex-smokers, 24.6 kg/m(2)
      for light smokers (1 to 9 cigarettes/d), 24.8 kg/m(2) for moderate smokers (10 to
      19 cigarettes/d), and 25.3 kg/m(2) for heavy smokers (> or =20 cigarettes/d) in
      men and 24.0, 24.1, 22.9, 22.9, and 23.3 kg/m(2), respectively, in women. Obesity
      (BMI > or = 30 kg/m(2)) was increasingly frequent with older age, lower physical
      activity, lower fruits/vegetables intake, and lower educational level. Compared
      with non-smokers, the odds ratio for obesity vs. normal weight (BMI = 18.5 to
      25.0 kg/m(2)) adjusted for age, nationality, educational level, leisure time
      physical activity, and fruit/vegetable intake were 1.9 (95% confidence interval:
      1.5 to 2.3) for ex-smokers, 0.5 (0.3 to 0.8) for light smokers, 0.7 (0.4 to 1.0)
      for moderate smokers, and 1.3 (1.0 to 1.7) for heavy smokers in men and 1.3 (1.1
      to 1.6), 0.7 (0.5 to 1.0), 0.8 (0.5 to 1.0), and 1.1 (0.8 to 1.4), respectively,
      in women. DISCUSSION: Among smokers, obesity was associated in a graded manner
      with the number of cigarettes daily smoked, particularly in men. More emphasis
      should be put on the risk of obesity among smokers.

PMID- 17495209
TI  - Evaluation of risk profiles by subcutaneous adipose tissue topography in obese
      juveniles.
AB  - OBJECTIVE: To compare subcutaneous adipose tissue topography (SAT-top) in obese
      juveniles with age-matched normal-weight controls. RESEARCH METHODS AND
      PROCEDURES: The optical device LIPOMETER (European Patent EP 0516251) enables the
      non-invasive, rapid, safe, and precise measurement of the thickness of
      subcutaneous adipose tissue. Fifteen defined body sites (1 = neck to 15 = calf)
      characterize the individual SAT-top like an individual fingerprint. SAT-top of
      1351 juveniles (obese: 42 boys, 59 girls, normal weight: 680 boys, 570 girls)
      from 7 to 19 years of age were measured. For visual comparison, the 15
      dimensional SAT-top information was condensed by factor analysis into a two
      dimensional factor plot. RESULTS: Both female and male obese juveniles had
      markedly increased adipose tissue layers at 7 = upper abdomen, 8 = lower abdomen,
      5 = front chest, and 6 = lateral chest. The pubertal changes of body shape and
      fat distribution of the normal-weight boys and girls (boys show thinner adipose
      tissue layers on their legs, whereas girls had thicker adipose tissue layers at
      the extremities) were not seen in the obese group. Independently of age and sex,
      all of the obese juveniles showed a similar, more android body fat distribution
      with increased trunk fat. DISCUSSION: SAT-top of the obese juveniles is similar
      to that of patients with type 2 diabetes, polycystic ovary syndrome, and coronary
      heart disease. Patients with these metabolic disorders and obese juveniles are
      located in the factor plot in the same area. This body shape may indicate a risk
      profile for developing polycystic ovary syndrome (women), type 2 diabetes, and
      early atherosclerosis (both sexes).

PMID- 17495210
TI  - A community intervention reduces BMI z-score in children: Shape Up Somerville
      first year results.
AB  - OBJECTIVE: The objective was to test the hypothesis that a community-based
      environmental change intervention could prevent weight gain in young children
      (7.6 +/- 1.0 years). RESEARCH METHODS AND PROCEDURES: A non-randomized controlled
      trial was conducted in three culturally diverse urban cities in Massachusetts.
      Somerville was the intervention community; two socio-demographically-matched
      cities were control communities. Children (n = 1178) in grades 1 to 3 attending
      public elementary schools participated in an intervention designed to bring the
      energy equation into balance by increasing physical activity options and
      availability of healthful foods within the before-, during-, after-school, home,
      and community environments. Many groups and individuals within the community
      (including children, parents, teachers, school food service providers, city
      departments, policy makers, healthcare providers, before- and after-school
      programs, restaurants, and the media) were engaged in the intervention. The main
      outcome measure was change in BMI z-score. RESULTS: At baseline, 44% (n = 385),
      36% (n = 561), and 43% (n = 232) of children were above the 85th percentile for
      BMI z-score in the intervention and the two control communities, respectively. In
      the intervention community, BMI z-score decreased by -0.1005 (p = 0.001, 95%
      confidence interval, -0.1151 to -0.0859) compared with children in the control
      communities after controlling for baseline covariates. DISCUSSION: A community
      based environmental change intervention decreased BMI z-score in children at high
      risk for obesity. These results are significant given the obesigenic
      environmental backdrop against which the intervention occurred. This model
      demonstrates promise for communities throughout the country confronted with
      escalating childhood obesity rates.

PMID- 17495212
TI  - Assessing resting metabolic rate using a multi-sensor armband.

PMID- 17495213
TI  - Mismatch and defuse: harvesting the riches of multicenter neuroimaging-based
      stroke studies.

PMID- 17495214
TI  - Anticoagulation in cerebral ischemia associated with intracranial artery
      dissections is safe, but is it enough to recommend it?

PMID- 17495215
TI  - Complex hemodynamics at the apex of an arterial bifurcation induces vascular
      remodeling resembling cerebral aneurysm initiation.
AB  - BACKGROUND AND PURPOSE: Arterial bifurcation apices are common sites for cerebral
      aneurysms, raising the possibility that the unique hemodynamic conditions
      associated with flow dividers predispose the apical vessel wall to aneurysm
      formation. This study sought to identify the specific hemodynamic insults that
      lead to maladaptive vascular remodeling associated with aneurysm development and
      to identify early remodeling events at the tissue and cellular levels. METHODS:
      We surgically created new branch points in the carotid vasculature of 6 female
      adult dogs. In vivo angiographic imaging and computational fluid dynamics
      simulations revealed the detailed hemodynamic microenvironment for each
      bifurcation, which were then spatially correlated with histologic features
      showing specific tissue responses. RESULTS: We observed 2 distinct patterns of
      vessel wall remodeling: (1) hyperplasia that formed an intimal pad at the
      bifurcation apex and (2) destructive remodeling in the adjacent region of flow
      acceleration that resembled the initiation of an intracranial aneurysm,
      characterized by disruption of the internal elastic lamina, loss of medial smooth
      muscle cells, reduced proliferation of smooth muscle cells, and loss of
      fibronectin. CONCLUSIONS: Strong localization of aneurysm-type remodeling to the
      region of accelerating flow suggests that a combination of high wall shear stress
      and a high gradient in wall shear stress represents a "dangerous" hemodynamic
      condition that predisposes the apical vessel wall to aneurysm formation.

PMID- 17495216
TI  - The 2006 William Feinberg lecture: shifting the paradigm from stroke to global
      vascular risk estimation.
AB  - By the year 2010, it is estimated that 18.1 million people worldwide will die
      annually because of cardiovascular diseases and stroke. "Global vascular risk"
      more broadly includes the multiple overlapping disease silos of stroke,
      myocardial infarction, peripheral arterial disease, and vascular death.
      Estimation of global vascular risk requires consideration of a variety of
      variables including demographics, environmental behaviors, and risk factors. Data
      from multiple studies suggest continuous linear relationships between the
      physiological vascular risk modulators of blood pressure, lipids, and blood
      glucose rather than treating these conditions as categorical risk factors.
      Constellations of risk factors may be more relevant than individual categorical
      components. Exciting work with novel risk factors may also have predictive value
      in estimates of global vascular risk. Advances in imaging have led to the
      measurement of subclinical conditions such as carotid intima-media thickness and
      subclinical brain conditions such as white matter hyperintensities and silent
      infarcts. These subclinical measurements may be intermediate stages in the
      transition from asymptomatic to symptomatic vascular events, appear to be
      associated with the fundamental vascular risk factors, and represent
      opportunities to more precisely quantitate disease progression. The expansion of
      studies in molecular epidemiology and detection of genetic markers underlying
      vascular risks also promises to extend our precision of global vascular risk
      estimation. Global vascular risk estimation will require quantitative methods
      that bundle these multi-dimensional data into more precise estimates of future
      risk. The power of genetic information coupled with data on demographics, risk
      inducing behaviors, vascular risk modulators, biomarkers, and measures of
      subclinical conditions should provide the most realistic approximation of an
      individual's future global vascular risk. The ultimate public health benefit,
      however, will depend on not only identification of global vascular risk but also
      the realization that we can modify this risk and prove the prediction models
      wrong.

PMID- 17495217
TI  - Evaluation of the clinical-diffusion and perfusion-diffusion mismatch models in
      DEFUSE.
AB  - BACKGROUND AND PURPOSE: The perfusion-diffusion mismatch (PDM) model has been
      proposed as a tool to select acute stroke patients who are most likely to benefit
      from reperfusion therapy. The clinical-diffusion mismatch (CDM) model is an
      alternative method that is technically less challenging because it does not
      require perfusion-weighted imaging. This study is an evaluation of these 2 models
      in the DEFUSE dataset. METHODS: DEFUSE is an open-label multicenter study in
      which acute stroke patients were treated with intravenous tPA between 3 and 6
      hours after symptoms onset and an MRI was obtained before and 3 to 6 hours after
      treatment. Presence of PDM and CDM was determined for each patient. RESULTS:
      Based on conventional predefined mismatch criteria, PDM was present in 54% of the
      DEFUSE population and CDM in 62%. There was no agreement beyond chance between
      the 2 mismatch models (kappa 0.07). The presence of PDM was associated with an
      increased chance of favorable clinical response after reperfusion (OR, 5.4;
      P=0.039). Reperfusion was not associated with a significant increase in the rate
      of favorable clinical response in patients with CDM (OR, 2.2; P=0.34). Using
      optimized mismatch criteria, determined retrospectively based on DEFUSE data, the
      OR for favorable clinical response was 70 (P=0.001) for PDM and 5.1 (P=0.066) for
      CDM. CONCLUSIONS: The PDM model appears to be more accurate than the CDM model
      for selecting patients who are likely to benefit from reperfusion therapy in the
      3- to 6-hour time window.

PMID- 17495218
TI  - Prognosis and safety of anticoagulation in intracranial artery dissections in
      adults.
AB  - BACKGROUND AND PURPOSE: To characterize different forms of intracranial artery
      dissections (IADs), and to test the assumption that IADs are frequently
      associated with subarachnoid hemorrhage (SAH) and poor outcome, and that
      anticoagulant therapy is contraindicated in these patients. METHODS: We studied
      81 consecutive non-SAH IAD patients and 22 IAD patients with SAH, diagnosed
      between 1994 and 2004 and 1998 and 2004, respectively, and treated the former
      patients immediately with heparin, followed with at least 3 months of warfarin.
      Outcomes were recorded at 3 months. RESULTS: Approximately one-third of all
      cervicocephalic artery dissections were identifiably either completely located
      intracranially or extended into the intracranial space. At 3 months, 64 of the 81
      non-SAH patients (79%) had a favorable outcome (modified Rankin Scale, 0 to 2); 1
      patient died of brain infarction in the acute stage. Only 1 aneurysm developed
      during follow-up in the non-SAH group, and no intracranial bleeding was observed
      during anticoagulant treatment. Those presenting with SAH formed approximately
      25% of all IADs, and 21 cases out of 22 (95%) were associated with ruptured
      fusiform dissecting aneurysm. This latter group displayed significantly worse
      outcomes: 7 died, and only 7 had modified Rankin Scale 0 to 2 at 3 months.
      CONCLUSIONS: Our results provide important information for clinical practice.
      IADs appear to polarize into 2 groups: (1) nonaneurysmatic IADs presenting
      without SAH that are associated with favorable outcomes and safe anticoagulant
      therapy; and (2) aneurysmatic IADs, characterized by SAH and poorer prognosis.
      Literature on IADs may have been biased toward group 2.

PMID- 17495219
TI  - Maternal and infant characteristics associated with perinatal arterial stroke in
      the preterm infant.
AB  - BACKGROUND AND PURPOSE: Most perinatal arterial stroke (PAS) studies that
      investigated infant characteristics have excluded preterm infants from the study
      population. We sought to analyze the imaging findings and antenatal and perinatal
      risk factors in preterm infants with PAS. METHODS: This was a hospital-based,
      case-control study of preterm infants. Case infants were confirmed by reviewing
      brain imaging scans and medical records (n=31). Three controls per case were
      individually matched with case infants from the study population. RESULTS:
      Gestational age ranged between 27 and 36 weeks, and birth weight ranged between
      580 and 3180 g. PAS was more common on the left side (61%), and 7% had bilateral
      PAS. The majority of strokes involved the middle cerebral artery distribution.
      Involvement of 1 or more lenticulostriate branches was most common among infants
      with a gestational age of 28 to 32 weeks, but main branch involvement was seen
      only in those with a gestational age of >32 weeks. Twin-to-twin-transfusion
      syndrome, fetal heart rate abnormality, and hypoglycemia were identified as
      independent risk factors for PAS. CONCLUSIONS: Preterm PAS is associated with
      prenatal, perinatal, and postpartum risk factors. We were unable to identify any
      maternal risk factors. Involvement of the different branches of the middle
      cerebral artery changed with an increase in gestational age.

PMID- 17495220
TI  - Therapy of basilar artery occlusion: individual protocols needed.

PMID- 17495221
TI  - Cyclin A2 induces cardiac regeneration after myocardial infarction and prevents
      heart failure.
AB  - Mammalian myocardial infarction is typically followed by scar formation with
      eventual ventricular dilation and heart failure. Here we present a novel model
      system in which mice constitutively expressing cyclin A2 in the myocardium elicit
      a regenerative response after infarction and exhibit significantly limited
      ventricular dilation with sustained and remarkably enhanced cardiac function. New
      cardiomyocyte formation was noted in the infarcted zones as well as cell cycle
      reentry of periinfarct myocardium with an increase in DNA synthesis and mitotic
      indices. The enhanced cardiac function was serially assessed over time by MRI.
      Furthermore, the constitutive expression of cyclin A2 appears to augment
      endogenous regenerative mechanisms via induction of side population cells with
      enhanced proliferative capacity. The ability of cultured transgenic
      cardiomyocytes to undergo cytokinesis provides mechanistic support for the
      regenerative capacity of cyclin A2.

PMID- 17495222
TI  - Substance P targets sympathetic control neurons in the paraventricular nucleus.
AB  - The paraventricular nucleus (PVN) contains spinally-projecting neurons implicated
      in fine-tuning the cardiovascular system. In vivo activity of "presympathetic"
      parvocellular neurons is suppressed by tonic inhibition from GABA-ergic inputs,
      inhibition of which increases sympathetic pressor activity and heart rate.
      Targeting of this specific neuronal population could potentially limit elevations
      of heart rate and blood pressure associated with disease. Here we show, for the
      first time, that "presympathetic" PVN neurons are disinhibited by the
      neuropeptide substance P (SP) acting via tachykinin NK1 receptor inhibition of
      GABA(A) currents. Application of SP to the paraventricular nucleus of rats
      increases heart rate and blood pressure. In in vitro brain slice experiments, in
      the presence of GABA, 1 micromol/L SP increased action current frequency by a
      factor of 2.7+/-0.6 (n=5, P< or =0.05, ANOVA). Furthermore, 1 micromol/L SP
      inhibited GABA(A) currents by 70+/-8% (n=8, P< or =0.005 paired t test). These
      effects were abolished by NK1 antagonists, but not NK2 and NK3 antagonists.
      GABA(A) inhibition was not reproduced by NK2 or NK3 agonists. The inhibition of
      parvocellular GABA(A) currents by SP was also abolished by a protein kinase C
      (PKC) inhibitor peptide and mimicked by application of phorbol-12-myristate-13
      acetate (PMA), implicating a PKC-dependent mechanism. Single-channel analysis
      indicates that SP acts through reduction of channel mean open-time (cmot):
      GABA(A) cmot being reduced by approximately 60% by SP (P< or =0.05 ANOVA,
      Bonferroni). These data suggest that tachykinins mediate their pressor activity
      by increasing the excitability of spinally-projecting neurons and identifies NK1
      receptors as potential targets for therapeutic modulation of the cardiovascular
      system.

PMID- 17495223
TI  - Nitrite reductase function of deoxymyoglobin: oxygen sensor and regulator of
      cardiac energetics and function.
AB  - Although the primary function of myoglobin (Mb) has been considered to be
      cellular oxygen storage and supply, recent studies have suggested to classify Mb
      as a multifunctional allosteric enzyme. In the heart, Mb acts as a potent
      scavenger of nitric oxide (NO) and contributes to the attenuation of oxidative
      damage. Here we report that a dynamic cycle exists in which a decrease in tissue
      oxygen tension drives the conversion of Mb from being an NO scavenger in normoxia
      to an NO producer in hypoxia. The NO generated by reaction of deoxygenated Mb
      with nitrite is functionally relevant and leads to a downregulation of cardiac
      energy status, which was not observed in mice lacking Mb. As a consequence,
      myocardial oxygen consumption is reduced and cardiac contractility is dampened in
      wild-type mice. We propose that this pathway represents a novel homeostatic
      mechanism by which a mismatch between oxygen supply and demand in muscle is
      translated into the fractional increase of deoxygenated Mb exhibiting enhanced
      nitrite reductase activity. Thus, Mb may act as an oxygen sensor which through NO
      can adjust muscle energetics to limited oxygen supply.

PMID- 17495224
TI  - Heme oxygenase-1 expression in macrophages plays a beneficial role in
      atherosclerosis.
AB  - Heme oxygenase (HO-1) is the rate-limiting enzyme in the catabolism of heme,
      which leads to the generation of biliverdin, iron, and carbon monoxide. It has
      been shown to have important antioxidant and antiinflammatory properties that
      result in a vascular antiatherogenic effect. To determine whether HO-1 expression
      in macrophages constitutes a significant component of the protective role in
      atherosclerosis, we evaluated the effect of decreased or absent HO-1 expression
      in peritoneal macrophages on oxidative stress and inflammation in vitro, and the
      effect of complete deficiency of HO-1 expression in macrophages in
      atherosclerotic lesion formation in vivo. We found that compared with HO-1(+/+)
      controls, peritoneal macrophages from HO-1(-/-) and HO-1(+/-) mice exhibited (1)
      increased reactive oxygen species (ROS) generation, (2) increased proinflammatory
      cytokines such as monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL
      6), and (3) increased foam cell formation when treated with oxLDL, attributable
      in part to increased expression of scavenger receptor A (SR-A). Bone marrow
      transplantation experiments performed in lethally irradiated LDL-R null female
      mice, reconstituted with bone marrow from HO-1(-/-) versus HO-1(+/+) mice,
      revealed that HO-1(-/-) reconstituted animals exhibited atherosclerotic lesions
      with a greater macrophage content as evaluated by immunohistochemistry and
      planimetric assessment. We conclude that HO-1 expression in macrophages
      constitutes an important component of the antiatherogenic effect by increasing
      antioxidant protection and decreasing the inflammatory component of
      atherosclerotic lesions.

PMID- 17495225
TI  - Inhibition of progression and stabilization of plaques by postnatal interferon
      gamma function blocking in ApoE-knockout mice.
AB  - A role of interferon-gamma is suggested in early development of atherosclerosis.
      However, the role of interferon-gamma in progression and destabilization of
      advanced atherosclerotic plaques remains unknown. Thus, the aim of this study was
      to determine whether postnatal inhibition of interferon-gamma signaling could
      inhibit progression of atherosclerotic plaques and stabilize the lipid- and
      macrophage-rich advanced plaques. Atherosclerotic plaques were induced in ApoE
      knockout (KO) mice by feeding high-fat diet from 8 weeks old (w). Interferon
      gamma function was postnatally inhibited by repeated gene transfers of a soluble
      mutant of interferon-gamma receptors (sIFNgammaR), an interferon-gamma inhibitory
      protein, into the thigh muscle every 2 weeks. When sIFNgammaR treatment was
      started at 12 w (atherosclerotic stage), sIFNgammaR not only prevented plaque
      progression but also stabilized advanced plaques at 16 w: sIFNgammaR decreased
      accumulations of the lipid and macrophages and increased fibrotic area with more
      smooth muscle cells. Moreover, sIFNgammaR downregulated expressions of
      proinflammatory cytokines, chemokines, adhesion molecules, and matrix
      metalloproteinases but upregulated procollagen type I. sIFNgammaR did not affect
      serum cholesterol levels. In conclusion, postnatal blocking of interferon-gamma
      function by sIFNgammaR treatment would be a new strategy to inhibit plaque
      progression and to stabilize advanced plaques through the antiinflammatory
      effects.

PMID- 17495226
TI  - Gene transfer of connexin43 mutants attenuates coupling in cardiomyocytes: novel
      basis for modulation of cardiac conduction by gene therapy.
AB  - Modification of electrical conduction would be a useful principle to recruit in
      preventing or treating certain arrhythmias, notably ventricular tachycardia (VT).
      Here we pursue a novel gene transfer approach to modulate electrical conduction
      by reducing gap junctional intercellular communication (GJIC) and hence
      potentially modify the arrhythmia substrate. The ultimate goal is to develop a
      nondestructive approach to uncouple zones of slow conduction by focal gene
      transfer. Lentiviral vectors encoding connexin43 (Cx43) internal loop mutants
      were produced and studied in vitro. Transduction of neonatal rat ventricular
      myocytes (NRVMs) revealed the expected subcellular localization of the mutant
      gene product. Fluorescent dye transfer studies showed a significant reduction of
      GJIC in NRVMs that had been genetically modified. Additionally, adjacent mutant
      gene-modified NRVMs displayed delayed calcium transients, indicative of
      electrical uncoupling. Multi-site optical mapping of action potential (AP)
      propagation in gene-modified NRVM monolayers revealed a 3-fold slowing of
      conduction velocity (CV) relative to nontransduced NRVMs. In conclusion,
      lentiviral vector-mediated gene transfer of Cx43 mutants reduced GJIC in NRVMs.
      Electrical charge transfer was also reduced as evidenced by delayed calcium
      transients in adjacent NRVMs and reduced CV in NRVM monolayers. These data
      validate a molecular tool that opens the prospect for gene transfer targeting gap
      junctions as an approach to modulate cardiac conduction.

PMID- 17495227
TI  - Cardiac sympathetic rejuvenation: a link between nerve function and cardiac
      hypertrophy.
AB  - Neuronal function and innervation density is regulated by target organ-derived
      neurotrophic factors. Although cardiac hypertrophy drastically alternates the
      expression of various growth factors such as endothelin-1, angiotensin II, and
      leukemia inhibitory factor, little is known about nerve growth factor expression
      and its effect on the cardiac sympathetic nerves. This study investigated the
      impact of pressure overload-induced cardiac hypertrophy on the innervation
      density and cellular function of cardiac sympathetic nerves, including kinetics
      of norepinephrine synthesis and reuptake, and neuronal gene expression. Right
      ventricular hypertrophy was induced by monocrotaline treatment in Wistar rats.
      Newly developed cardiac sympathetic nerves expressing beta(3)-tubulin (axonal
      marker), GAP43 (growth-associated cone marker), and tyrosine hydroxylase were
      markedly increased only in the right ventricle, in parallel with nerve growth
      factor upregulation. However, norepinephrine and dopamine content was
      paradoxically attenuated, and the protein and kinase activity of tyrosine
      hydroxylase were markedly downregulated in the right ventricle. The reuptake of
      [(125)I]-metaiodobenzylguanidine and [(3)H]-norepinephrine were also
      significantly diminished in the right ventricle, indicating functional
      downregulation in cardiac sympathetic nerves. Interestingly, we found cardiac
      sympathetic nerves in hypertrophic right ventricles strongly expressed highly
      polysialylated neural cell adhesion molecule (PSA-NCAM) (an immature neuron
      marker) as well as neonatal heart. Taken together, pressure overload induced
      anatomical sympathetic hyperinnervation but simultaneously caused deterioration
      of neuronal cellular function. This phenomenon was explained by the rejuvenation
      of cardiac sympathetic nerves as well as the hypertrophic cardiomyocytes, which
      also showed the fetal form gene expression.

PMID- 17495228
TI  - A three-kilobase fragment of the human Robo4 promoter directs cell type-specific
      expression in endothelium.
AB  - Robo4, a member of the roundabout family, is expressed exclusively in endothelial
      cells and has been implicated in endothelial cell migration and angiogenesis.
      Here we report the cloning and characterization of the human Robo4 promoter. The
      3-kb 5'-flanking region directs endothelial cell-specific expression in vitro.
      Deletion and mutation analyses revealed the functional importance of two 12-bp
      palindromic DNA sequences at -2528 and -2941, 2 SP1 consensus motifs at -42 and 
      153, and an ETS consensus motif at -119. In electrophoretic mobility shift assays
      using supershifting antibodies, the SP1 motifs bound SP1 protein, whereas the ETS
      site bound a heterodimeric member of the ETS family, GA binding protein (GABP).
      These DNA-protein interactions were confirmed by chromatin immunoprecipitation
      assays. Transfection of primary human endothelial cells with small interfering
      RNA against GABP and SP1 resulted in a significant (approximately 50%) reduction
      in endogenous Robo4 mRNA expression. The 3-kb Robo4 promoter was coupled to LacZ,
      and the resulting cassette was introduced into the Hprt locus of mice by
      homologous recombination. Reporter gene activity was observed in the vasculature
      of adult organs (particularly in microvessels), tumor xenografts, and embryos,
      where it colocalized with the endothelial cell-specific marker CD31. LacZ mRNA
      levels in adult tissues and tumors correlated with mRNA levels for endogenous
      Robo4, CD31, and vascular endothelial cadherin. Moreover, the pattern of reporter
      gene expression was similar to that observed in mice in which LacZ was knocked
      into the endogenous Robo4 locus. Together, these data suggest that 3-kb upstream
      promoter of human Robo4 contains information for cell type-specific expression in
      the intact endothelium.

PMID- 17495229
TI  - Effect of cell-based intercellular delivery of transcription factor GATA4 on
      ischemic cardiomyopathy.
AB  - Recent loss-of-function studies highlight the importance of the transcription
      factor GATA4 in the myocardial response to injury in the adult heart. However,
      the potential effects of gain-in-function of GATA4 overexpression, and
      transcription factors in general, is hindered by the fact that transcription
      factors are neither secreted nor taken up by cells. Chimeric proteins
      incorporating motifs of cell-penetrating proteins are secreted from cells and
      internalized by surrounding cells. We engineered a chimeric protein consisting of
      GATA4 and the cell-penetrating protein VP22. Cardiac fibroblasts stably
      transfected with the GATA4:VP22, GFP:VP22, or green fluorescent protein (GFP)
      constructs were transplanted into Lewis rats 1 month after left anterior
      descending ligation. GATA4:VP22 expression in the border zone was associated with
      increased cardiac myosin expression and cardiac myocyte size (30 mum versus 19
      mum, P<0.01). Compared with the GFP:VP22 control group, 6 weeks after cardiac
      fibroblast transplantation (10 weeks after myocardial infarction), animals that
      received GATA4:VP22-expressing cardiac fibroblasts demonstrated increased cardiac
      function and less negative remodeling. These data demonstrate a novel strategy
      for transcription factor delivery to injured myocardium and indicate that the
      delivery of GATA4 locally to the infarct border zone induces multiple local
      effects in the border zone cardiac myocytes resulting in beneficial ventricular
      remodeling and improved global left ventricular function.

PMID- 17495230
TI  - Endothelial progenitor cells: sowing the seeds for vascular repair.

PMID- 17495231
TI  - Hypoplastic left heart syndrome: new insights.

PMID- 17495233
TI  - Clinical aspects of platelet inhibitors and thrombus formation.
AB  - The platelet, once thought to be solely involved in clot formation, is now known
      to be a key mediator in various others processes such as inflammation,
      thrombosis, and atherosclerosis. Supported by the wealth of evidence from
      clinical trials demonstrating their benefits in patient outcomes, antiplatelet
      agents have become paramount in the prevention and management of various diseases
      involving the cardiovascular, cerebrovascular, and peripheral arterial systems.
      Despite being among the most widely used and studied classes of medical
      therapies, new discoveries regarding important clinical aspects and properties of
      these agents continue to be made. As our understanding of platelet biology
      expands, more effective and safer novel therapies continue to be developed. The
      use of more refined agents in conjunction with a better understanding of their
      effects will further the ability to provide more optimized care on an individual
      basis.

PMID- 17495232
TI  - Adipose-derived stem cells for regenerative medicine.
AB  - The emerging field of regenerative medicine will require a reliable source of
      stem cells in addition to biomaterial scaffolds and cytokine growth factors.
      Adipose tissue represents an abundant and accessible source of adult stem cells
      with the ability to differentiate along multiple lineage pathways. The isolation,
      characterization, and preclinical and clinical application of adipose-derived
      stem cells (ASCs) are reviewed in this article.

PMID- 17495234
TI  - Ubiquitin and ubiquitin-like proteins in protein regulation.
AB  - The discovery of the ubiquitin system was awarded with the Nobel Prize in
      Chemistry in 2004. Labeling of intracellular proteins for degradation by a
      multienzymatic complex, called the proteasome, was identified as the main
      function of this system. Subsequently, it was discovered that the attachment of
      ubiquitin to proteins can modify their function without degradation. Finally, a
      number of other molecules were recognized to be conjugated to proteins in a
      manner similar to ubiquitin and were henceforth called ubiquitin-like proteins.
      This review provides an overview of this class of molecules and its implication
      for function, subcellular location, and half-life of proteins.

PMID- 17495235
TI  - Endothelial outgrowth cells are not derived from CD133+ cells or CD45+
      hematopoietic precursors.
AB  - OBJECTIVE: Two types of endothelial progenitor cells (EPCs), early EPCs and late
      EPCs (also called endothelial outgrowth cells [EOCs]), were described in vitro
      previously. In this report, we dissect the phenotype of the precursor(s) that
      generate these cell types with focus on the markers CD34, CD133, and vascular
      endothelial growth factor receptor-2 (VEGFR2) that have been used to identify
      putative circulating endothelial precursors. We also included CD45 in the
      analysis to assess the relation between CD34+ hematopoietic progenitors (HPC),
      CD34+ endothelial precursors, and both in vitro generated EPC types. Addressing
      this issue might lead to a better understanding of the lineage and phenotype of
      the precursor(s) that give rise to both cell types in vitro and may contribute to
      a consensus on their flowcytometric enumeration. METHODS AND RESULTS: Using cell
      sorting of human cord blood (UCB) and bone marrow (BM) cells, we demonstrate that
      EOC generating precursors are confined to a small CD34+ CD45- cell fraction, but
      not to the CD34+ CD45+ HPC fraction, nor any other CD45+ subpopulation. CD34+
      CD45+ HPC generated monocytic cells that displayed characteristics typical for
      early EPCs. Phenotypic analysis showed that EOC generating CD34+ CD45- cells
      express VEGFR2 but not CD133, whereas CD34+ CD45+ HPC express CD133 as expected,
      but not VEGFR2. CONCLUSION: EOCs are not derived from CD133+ cells or CD45+
      hematopoietic precursors.

PMID- 17495236
TI  - Cooperation of SRC-1 and p300 with NF-kappaB and CREB in angiotensin II-induced
      IL-6 expression in vascular smooth muscle cells.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of coactivator
      histone acetyltransferases (HATs) p300 and SRC-1 in angiotensin II (Ang II)
      induced interleukin-6 (IL-6) gene expression in vascular smooth muscle cells
      (VSMCs). METHODS AND RESULTS: Ang II increased IL-6 mRNA expression via NF-kappaB
      and CREB in an extracellular signal-regulated kinase (ERK)-dependent manner in
      rat VSMCs. It was also significantly enhanced by the histone deacetylase
      inhibitor, Trichostatin A. Chromatin immunoprecipitation (ChIP) assays showed
      that Ang II increased Histone H3 Lysine (K9/14) acetylation on the IL-6 promoter.
      Ang II-induced IL-6 promoter transactivation was significantly enhanced by p300
      and SRC-1, with maximal activation in cells cotransfected with NF-kappaB (p65)
      and SRC-1. Nucleofection of VSMCs with either an ERK phosphorylation site mutant
      of SRC-1 or p300/CBP HAT deficient mutants significantly blocked Ang II-induced
      IL-6 expression. ChIP assays revealed that Ang II enhanced coordinate occupancy
      of p65, CREB, p300, and SRC-1 at the IL-6 promoter. An ERK pathway inhibitor
      blocked Ang-induced IL-6 promoter SRC-1 occupancy and histone acetylation.
      CONCLUSIONS: Ang II-induced IL-6 expression requires NF-kappaB and CREB as well
      as ERK-dependent histone acetylation mediated by p300 and SRC-1. These results
      provide new insights into nuclear chromatin mechanisms by which Ang II regulates
      inflammatory gene expression.

PMID- 17495237
TI  - Type A eagerness-energy across developmental periods predicts adulthood carotid
      intima-media thickness: the Cardiovascular Risk in Young Finns Study.
AB  - OBJECTIVE: We examined the Type A behavior across developmental periods as a
      predictor of adult carotid artery intima-media thickness (IMT). METHODS AND
      RESULTS: In this prospective cohort study of 408 men and 606 women, socioeconomic
      background and biological risk factors of participants were assessed at baseline
      at age 6 to 18 years of age, Type A behavior (Hunter-Wolf A-B Rating Scale) at
      the 6-, 9-, and 21-year follow-ups (subjects being 12 to 24, 15 to 27, and 27 to
      39 years, respectively), and carotid IMT, adulthood socioeconomic situation, and
      biological risk factors at the 21-year follow-up when participants were at age 27
      to 39 years of age. In men, the eagerness-energy component of Type A behavior,
      measured at any time point, was associated with thicker carotid IMT (P<0.008,
      P<0.04, P<0.03, and P<0.02 for the first, second, and third assessment, and for
      the average score, respectively), and this association was independent of early
      and adult risk factors. In women, the hard-driving component at baseline (P<0.04)
      but not later was independently related to thinner carotid IMT. The other
      components of Type A behavior (impatience-aggression and leadership) were not
      associated with IMT. CONCLUSIONS: Eagerness-energy component of Type A behavior
      over different developmental transitions seems to be a robust predictor of IMT in
      men.

PMID- 17495238
TI  - Elevated cholesterol levels in the plasma membranes of macrophages inhibit
      migration by disrupting RhoA regulation.
AB  - OBJECTIVE: Atherogenesis begins as small subendothelial accumulations of foam
      cells that develop through unregulated uptake of modified and aggregated low
      density lipoprotein (LDL). The reason why foam cells remain in the
      atherosclerotic plaque rather than migrating out of the area is unclear. We
      tested the hypothesis that elevated membrane cholesterol levels, which may result
      from interactions with aggregated LDL, affect macrophage migration. METHODS AND
      RESULTS: Cholesterol loading by incubation with cholesterol-chelated methyl-beta
      cyclodextrin decreased migration of J774A.1 macrophages toward complement 5a
      (C5a) in transwell migration assays, even though cholesterol-loaded macrophages
      responded to a bath application of C5a. In a micropipette polarization assay,
      cholesterol-loaded cells polarized toward a C5a gradient. In a transwell
      migration assay, cholesterol-loaded cells extended lamellae through the filter
      pores but were unable to translocate their cell bodies. Cholesterol loading
      decreased both the cellular levels of GTP-bound active RhoA and the
      phosphorylation of myosin light chain. Expression of constitutively active RhoA
      largely prevented the inhibition of cell migration by cholesterol loading.
      CONCLUSIONS: These results suggest that increases in plasma membrane cholesterol
      content alter RhoA activation, resulting in inhibition of cell migration. These
      findings provide one possible explanation for the retention of foam cells in
      atherosclerotic lesions.

PMID- 17495239
TI  - The expression of adult ADHD symptoms in daily life: an application of experience
      sampling methodology.
AB  - OBJECTIVE: To use experience sampling method (ESM) to examine the impact of
      inattentive and hyperactive-impulsive ADHD symptoms on emotional well-being,
      activities and distress, cognitive impairment, and social functioning assessed in
      the daily lives of young adults. The impact of subjective appraisals on their
      experiences is also examined. METHOD: Participants (n = 206) complete up to 56 in
      the-moment assessments of mood and current activities using Personal Digital
      Assistants for 1 week. RESULTS: Multilevel modeling techniques reveal that ADHD
      inattentive and hyperactive-impulsive symptoms differentially relate to daily
      experiences. Higher inattentive symptoms are associated with indices of general
      distress, including less positive and more negative mood as well as more
      concentration problems. Higher hyperactive-impulsive symptoms are associated with
      reduced sensitivity to contextual factors in perceptions of situations.
      CONCLUSION: These findings demonstrate predictive validity for adult self-report
      of ADHD symptoms in a general population sample and suggest future research
      directions using ESM.

PMID- 17495240
TI  - A comparative study of performance in the Conners' Continuous Performance Test
      between Brazilian and North American children.
AB  - OBJECTIVE: The present study investigated the performance of Brazilian children
      in the Continuous Performance Test, CPT-II, and compared results to those of the
      norms obtained in the United States. METHOD: The U.S. norms were compared to
      those of a Brazilian sample composed of 6- to 11-year-olds separated into 4 age
      groups (half boys) that represented the socioeconomic class distribution of Sao
      Paulo City. The children were prescreened for attention deficit disorders (ADHD).
      RESULTS: Age and gender effects in the Brazilian sample were similar to those
      previously described. However, the Brazilian sample showed better performance in
      almost all measures in all age-groups compared to that of the United States.
      CONCLUSION: It is discussed that differences between samples probably reflect
      lack of ADHD screening of the U.S. children. More studies are necessary to
      determine if the CPT-II is a cross-cultural test with participants from different
      samples matched for age, gender, and socioeconomic status screened for ADHD.

PMID- 17495241
TI  - Localization of thymosin beta-4 in tumors.
AB  - Overexpression of thymosin beta-4 has been linked to malignant progression but
      the localization of this polypeptide within tumors is incompletely known. We
      therefore examined breast cancers for thymosin beta-4 using immunofluorescence.
      Reactive cells were identified with monoclonal cell marker antibodies. A very
      heterogeneous staining pattern for thymosin beta-4 was observed. Thus, while
      leukocytes and macrophages showed intense reactivity for this polypeptide, cancer
      cells, and endothelial cells showed a much more variable reactivity. A similar
      heterogeneous staining was observed also in colorectal carcinomas. The degree of
      staining of breast cancer cells for thymosin beta-4 correlated neither to
      histological grade nor to endothelial cell staining. However, there was a
      tendency toward correlation (P = 0.07) between staining of endothelial cells and
      histological grade. Treatment of cultured breast cancer cells (SK-BR-3) with 1-4
      microg thymosin beta-4/mL significantly increased cell numbers, as determined by
      MTT-assays. These data reveal an unexpected cellular heterogeneity of thymosin
      beta-4 expression in breast and colonic carcinomas and suggest that local release
      of this polypeptide in the tumor microenvironment may modulate tumor behavior.

PMID- 17495242
TI  - Thymosin alpha1: an endogenous regulator of inflammation, immunity, and
      tolerance.
AB  - Thymosin alpha1 (Talpha1), first described and characterized by Allan Goldstein
      in 1972, is used worldwide for the treatment of some immunodeficiencies,
      malignancies, and infections. Although Talpha1 has shown a variety of effects on
      cells and pathways of the immune system, its central role in modulating dendritic
      cell (DC) function has only recently been appreciated. As DCs have the ability to
      sense infection and tissue stress and to translate collectively this information
      into an appropriate immune response, an action on DCs would predict a central
      role for Talpha1 in inducing different forms of immunity and tolerance. Recent
      results have shown that Talpha1: (a) primed DCs for antifungal Th1 resistance
      through Toll-like receptor (TLR)/MyD88-dependent signaling and this translated in
      vivo in protection against aspergillosis; (b) activated plasmacytoid DCs (pDC)
      via the TLR9/MyD88-dependent viral recognition, thus leading to the activation of
      interferon regulatory factor 7 and the promotion of the IFN-alpha/IFN-gamma
      dependent effector pathway, which resulted in vivo in protection against primary
      murine cytomegalovirus infection; (c) induced indoleamine 2,3-dioxygenase
      activity in DCs, thus affecting tolerization toward self as well as microbial non
      self-antigens, and this resulted in vivo in transplantation tolerance and
      protection from inflammatory allergy. Talpha1 is produced in vivo by cleavage of
      prothymosin alpha in diverse mammalian tissues. Our data qualify Talpha1 as an
      endogenous regulator of immune homeostasis and suggest that instructive
      immunotherapy with Talpha1, via DCs and tryptophan catabolism, could be at work
      to control inflammation, immunity, and tolerance in a variety of clinical
      settings.

PMID- 17495243
TI  - Thymosin beta4 is not always the main beta-thymosin in mammalian platelets.
AB  - beta-thymosins constitute a family of highly conserved 5-kDa polypeptides.
      Thymosin beta(4), the most abundant member of this family, is expressed in most
      mammalian cell types and is regarded as the main intracellular G-actin
      sequestering peptide. In addition to this important intracellular function
      several other activities have been attributed to this peptide. Thymosin beta(4)
      is released from human platelets and cross-linked to fibrin after activation of
      platelets with thrombin. While in most mammalian tissues thymosin beta(4) is
      accompanied by a second member of this peptide family, in human platelets only
      thymosin beta(4) is present. To elucidate if it is common to mammalian platelets
      that only one beta-thymosin is present, we analyzed platelets from several
      mammals for their beta-thymosin content. In human platelets only thymosin beta(4)
      could be detected, whereas in bovine platelets thymosin beta(9), which is
      normally the minor beta-thymosin in bovine tissues, was identified as the main
      beta-thymosin. In rabbit platelets, thymosin beta(4) is not simply replaced by
      the most homologous thymosin beta(4)(Ala), as might be expected from sequence
      homology. Thymosin beta(4)(Ala) and thymosin beta(10) were found, but thymosin
      beta(10) is present in about 2.5-fold higher amounts. Because thymosin
      beta(4)(Ala) possesses about threefold higher affinity to G-actin, compared to
      thymosin beta(4), beta(10), and beta(9), we suggest that expression of beta
      thymosins is triggered by functional requirements and not sequence homology.

PMID- 17495244
TI  - Determination of thymosin beta4 and protein in human wound fluid after abdominal
      surgery.
AB  - Wound fluids were collected up to 60 h after abdominal surgery. Immediately after
      obtaining the wound fluid by Robinson drainage, wound fluid was centrifuged to
      remove blood cells and inflammatory cells. The concentration of total protein as
      well as of thymosin beta(4) was determined in the cell-free supernatant solution.
      Total protein concentration decreased from about 50 g/L to 30 g/L within 60 h
      after surgery. After surgery we observed a concentration of up to 20 mg thymosin
      beta(4) per liter decreasing to about 1 mg/L with time. Neither thymosin beta(10)
      nor oxidized thymosin beta(4) was detected in human wound fluid.

PMID- 17495245
TI  - Adhesive and proteolytic phenotype of migrating endothelial cells induced by
      thymosin beta-4.
AB  - The early stages of angiogenesis are usually accompanied by the occurrence of
      vascular leakage, and the deposition of fibrin in extravascular spaces.
      Initially, the fibrin network acts as a sealing matrix, but later on also as a
      scaffolding for invading endothelial cells. This process is induced by angiogenic
      growth factors, particularly by vascular endothelial growth factor (VEGF).
      Angiogenesis involves proteolytic activities, in particular cell-bound
      urokinase/plasmin and matrix metalloproteinase (MMPs) activities that modulate
      the fibrin structure and affect adhesion and migration of endothelial cells.
      Recent data show that formation of new vessels may be stimulated by thymosin beta
      4 (Tbeta-4), but it is still not clear whether Tbeta-4 alone is angiogenic or the
      angiogenic potential of Tbeta-4 is mediated by VEGF. In this report to further
      characterize Tbeta-4 angiogenic activity, we produced its mutants that were
      deprived of the N-terminal tetrapeptide AcSDKP (Tbeta-4((AcSDKPT/4A))), the actin
      binding sequence KLKKTET (Tbeta-4((KLKKTET/7A))) and with the nuclear
      localization sequence damaged by a point mutation Lys16Ala (Tbeta-4((K16A))).
      Then we tested their activity to induce expression and release of MMPs as well as
      plasminogen activators inhibitor type-1 (PAI-1). We also analyzed their effect on
      migration and proliferation of endothelial cells in three-dimensional (3D) fibrin
      matrix as well as on their ability to stimulate the outgrowth of human
      endothelial cells in capillary-like tubular structures. Our data demonstrate that
      increased intracellular expression of Tbeta-4 and its mutants is necessary and
      sufficient to induce PAI-1 gene expression in endothelial cells. Similarly, they
      stimulate expression and release of MMP-1, -2, and -3. As evaluated by using
      specific inhibitors to these MMPs, they modified specifically the structure of
      fibrin and thus facilitated migration of endothelial cells. To sum up, our data
      show that the mechanism by which Tbeta-4 induced transition of endothelial cells
      from quiescent to proangiogenic phenotype is characterized by increased
      expression of PAI-1 and MMPs did not require the presence of the N-terminal
      sequence AcSDKP, and depended only partially on its ability to bind G-actin or to
      enter the nucleus.

PMID- 17495246
TI  - In vivo sampling of extracellular beta-thymosin by ultrafiltration probes.
AB  - In vivo detection and monitoring of extracellular beta-thymosin will facilitate
      the understanding of their biological function and association with disease
      progression. A novel technique using capillary ultrafiltration (CUF) probes
      linked to mass spectrometry is capable of sensing extracellular thymosin beta-4
      and/or thymosin beta-10 in vivo in wounded skin and other tissue
      microenvironments. In this review, we highlight the association of extracellular
      beta-thymosin with skin wound healing and the potential adjuvant effects on
      vaccination. The fabrication and biological application of CUF probes are also
      described. Data from CUF probe-captured beta-thymosin may guide future
      exploration of extracellular beta-thymosin.

PMID- 17495247
TI  - Function of prothymosin alpha in chromatin decondensation and expression of
      thymosin beta-4 linked to angiogenesis and synaptic plasticity.
AB  - Prothymosin alpha (ProTalpha) is an abundant highly acidic protein found in the
      nuclei of virtually all mammalian cells. The expression of this protein is
      increased in proliferating mammalian cells. However, the function of this
      molecule is still controversial. Here I present a model explaining the role of
      this protein in chromatin decondensation through its interaction with histone H1.
      beta-thymosins are a family of small actin-binding peptides widely distributed in
      eukaryotic cells. Here I will focus on thymosin beta-4, the most abundant member
      of this family. In particular, I will discuss its expression in the mammalian
      development of cardiovascular and nervous systems as well as its implications in
      neuronal plasticity.

PMID- 17495248
TI  - The beta-thymosin enigma.
AB  - Actin dynamics in nonmuscle cells is controlled by the availability of actin
      nucleating sites and actin monomers. Thymosin beta-4 (Tbeta-4) has been
      implicated in modulating the availability of actin monomers in a large variety of
      cells. It together with actin nucleating, severing, and uncapping proteins,
      harnesses the intrinsic dynamic properties of actin to regulate the actin
      polymerization response in cells. Overexpression or addition of exogenous Tbeta-4
      or its homolog, Tbeta-10, alters the actin cytoskeleton, and has multiple effects
      on cellular functions related to motility. Some of these effects are consistent
      with beta-thymosins functioning exclusively as monomer-binding proteins, while
      others are not. Therefore, the complex pleiotropic effects of beta-thymosin in
      cells may be due to direct and indirect effects on the actin cytoskeleton, as
      well as modulation of signaling pathways that will impact the cytoskeleton and a
      variety of cell functions.

PMID- 17495249
TI  - Thymosin beta-4 and the eye: I can see clearly now the pain is gone.
AB  - The cornea epithelium responds to injury by synthesizing several cytokines,
      growth factors, and tissue remodeling molecules. Proinflammatory cytokines have
      been implicated in the inflammation that follows corneal epithelial injury and
      cytokine-mediated processes play a significant role in corneal epithelial wound
      healing. Poorly regulated corneal inflammatory reactions that occur after injury
      can retard healing. In turn, persistent corneal epithelial defects and
      inflammation may lead to ocular morbidity and permanent visual loss. Therefore,
      treatments with agents that enhance corneal reepithelialization and regulate the
      inflammatory response without the deleterious side effects of currently used
      agents, such as corticosteroids, would result in improved clinical outcome and
      would represent a major advance in the field. Evidence is mounting to support the
      idea that thymosin beta-4 (Tbeta-4) has multiple, seemingly diverse, cellular
      functions. In the cornea, as in other tissues, Tbeta-4 promotes cell migration
      and wound healing, has anti-inflammatory properties, and suppresses apoptosis.
      Prior studies from our laboratory have demonstrated the potent wound healing and
      anti-inflammatory effects of Tbeta-4 in numerous models of corneal injury.
      Recently, we demonstrated that Tbeta-4 suppresses the activation of the
      transcription factor, nuclear factor-kappa b (NF-kappaB) in TNF-alpha-stimulated
      cells. TNF-alpha initiates cell signaling pathways that converge on the
      activation of NF-kappaB, thus both are known mediators of the inflammatory
      process. These results have important clinical implications for the potential
      role of Tbeta-4 as a corneal anti-inflammatory and wound-healing agent.

PMID- 17495250
TI  - Thymosin beta-4 and venous ulcers: clinical remarks on a European prospective,
      randomized study on safety, tolerability, and enhancement on healing.
AB  - The objective of this double-blind, placebo-controlled, dose-escalation study is
      to evaluate safety, tolerability, and enhancement on healing of thymosin beta-4
      (Tbeta-4) administered topically in patients with venous ulcers. Three groups of
      patients, coming from 10 sites, 5 from Italy and 5 from Poland, will be enrolled
      sequentially. Twenty-four patients within each group will be randomized to Tbeta
      4 or placebo in a 3:1 ratio and will be treated with increasing doses of Tbeta-4.
      When review safety data show no-dose-limiting adverse events, a new group will be
      enrolled. So, the study design comprehends 72 patients treated for 84 days and
      followed for 14 days at the end of treatment. Blood samples will be taken on day
      0 and at the end of treatment visit to measure plasma levels of Tbeta-4. Every
      week each patient is visited and blood samples are taken for clinical chemistry,
      hematology, coagulation, and urinalysis. Each ulcer is treated with debridement,
      if necessary, and compression therapy with standard compression stockings class
      2. Efficacy parameters are incidence of healing defined as the percentage of
      patients who have complete closure of the index ulcer at day 84 and, mean time to
      complete healing. Ulcer area will be calculated by digital planimetry and
      photographic analysis. The study is ongoing and a total of 21 patients have been
      enrolled so far in the first treatment group at the lower dose. Patients'
      compliance and motivated and well-trained teams seem to be the most suitable
      parameters of a successfully conducted study.

PMID- 17495251
TI  - Influence of the N terminus and the actin-binding motif of thymosin beta4 on its
      interaction with G-actin.
AB  - Thymosin beta(4) binds G-actin in a 1:1 ratio and prevents its aggregation to F
      actin by sequestration. Substitution or modification of single amino acid
      residues within the N-terminal sequence 1 to 22 of thymosin beta(4) alters its
      interaction with G-actin. We generated thymosin beta(4) variants with amino acid
      substitutions within the N-terminal alpha-helix and the putative actin-binding
      motif. None of the E. coli-generated thymosin beta(4) variants was modified or
      acetylated at its N terminus. The stability of the complex of G-actin with
      nonacetylated thymosin beta(4) or beta(4)(A7V) is higher than the one with
      naturally occurring thymosin beta(4), which is always acetylated. The complex of
      G-actin with nonacetylated thymosin beta(4)(A7V,K18,19A) and
      beta(4)(K14,16,18,19A) is 15 times less stable compared to the complex with
      thymosin beta(4). The G-actin sequestering activities of all thymosin beta(4)
      variants correspond to their complex stabilities with G-actin, except for
      nonacetylated thymosin beta(4)(A7V), where it is attenuated. Thymosin
      beta(4)(Delta17-23) missing the putative actin-binding motif shows no interaction
      with G-actin.

PMID- 17495252
TI  - Thymosin beta-4 is essential for coronary vessel development and promotes
      neovascularization via adult epicardium.
AB  - Ischemic heart disease leading to myocardial infarction causes irreversible cell
      loss and scarring and is a major cause of morbidity and mortality in humans.
      Significant effort in the field of cardiovascular medicine has been invested in
      the search for adult cardiac progenitor cells that may replace damaged muscle
      cells and/or contribute to new vessel formation (neovascularization) and in the
      identification of key factors, which may induce such progenitor cells to
      contribute to myocardial repair and collateral vessel growth. We recently
      demonstrated that the actin monomer-binding protein, thymosin beta-4 (Tbeta-4),
      when secreted from the myocardium provides a paracrine stimulus to the cells of
      the epicardium-derived cells (EPDCs) to promote their inward migration and
      differentiation into endothelial and smooth muscle cells to form the coronary
      vasculature. Translating this essential role for Tbeta-4 in coronary vessel
      development to the adult, we found that treatment of cultured adult explants with
      Tbeta-4 stimulated extensive outgrowth of epicardin-positive epicardial cells,
      which, as they migrated away from the explant, differentiated into procollagen
      type I, SMalphaA, and Flk1-positive cells indicative of fibroblasts, smooth
      muscle, and endothelial cells; thus releasing the adult epicardium from a
      quiescent state and restoring pluripotency. The ability of Tbeta-4 to promote
      coronary vessel development and potentially induce new vasculature in the adult
      is essential for cardiomyocyte survival and could contribute significantly toward
      the reported Tbeta4-induced cardioprotection and repair in the adult heart. Tbeta
      4 is currently subject to multicenter phase 1 clinical trials for treatment of
      cardiovascular disease (http://www.regenerx.com), therefore, insight into the
      repair mechanism(s) induced by Tbeta-4 is an essential step toward harnessing
      therapeutic survival, migration, and repair properties of the peptide in the
      context of acute myocardial damage.

PMID- 17495253
TI  - Pathophysiological basis of right ventricular remodeling.
AB  - The pathophysiology of right ventricular (RV) remodeling is a complex process and
      may include unique elements not observed in left ventricular (LV) remodeling. The
      RV also has a relatively irregular geometry not accounted for in LV analyses. RV
      remodeling includes basic changes in geometry, wall thickness, and ventricular
      pressure-volume relationships. Also, myocyte dimensions and number increase, and
      myocardial extracellular matrix and biochemical milieu are modified. Remodeling
      has been associated with such diseases as pulmonary hypertension, lung
      transplant, LV pathology, Chagas' disease, and arrhythmogenic right ventricular
      cardiomyopathy. Disease progression may lead to further RV changes, including
      hypertrophy, dilatation, and subsequently to variable alterations in RV
      hemodynamic status. The multiple methods to assess RV hypertrophy include cine
      magnetic resonance imaging and 3-D echocardiography. Each technique offers
      different precision in evaluating RV dimensions and functional performance
      characteristics. Strategies to prevent RV remodeling include pharmacological
      agents, such as vasodilators and angiotensin-converting enzyme inhibitors, as
      well as more invasive interventions, such as ventricular assist devices.

PMID- 17495254
TI  - A review of the investigational antiarrhythmic agent dronedarone.
AB  - Arrhythmias are a major cause of morbidity and mortality, and atrial fibrillation
      is the most widespread disorder of cardiac rhythm. Amiodarone is an effective
      antiarrhythmic agent that has been in clinical use for about 20 years. It is
      effective for multiple types of arrhythmias, including atrial fibrillation, and
      has a low incidence of cardiac adverse events, including Torsade de Pointes. It
      has many noncardiac adverse effects that are serious and limit its long-term use.
      Dronedarone is an investigational antiarrhythmic agent that is designed to have
      similar cardiac effects to amiodarone but with fewer adverse effects. This review
      presents some of the animal and human studies that evaluate the effects of
      dronedarone.

PMID- 17495255
TI  - Lipid-lowering therapy and outcomes in heart failure.
AB  - Lipid-lowering therapy, particularly with statins, reduces the risk of
      cardiovascular mortality; however, there is uncertainty about their efficacy in
      patients with heart failure, including those without coronary artery stenosis. A
      clinical database was studied to determine whether lipid-lowering therapy is
      associated with improved survival in persons with heart failure-with or without
      concomitant coronary artery stenosis. During an 8-year period, 6060 people with a
      history of heart failure underwent coronary angiography. At the time of
      angiography, 1216 received a lipid-lowering agent. During a median follow-up of
      4.7 years, 7.1 deaths per 100 person-years occurred among users of lipid-lowering
      therapy, compared with 7.8 per 100 person-years among nonusers (adjusted hazard
      ratio 0.87, 95% confidence interval 0.77-0.97). Use of lipid-lowering therapy was
      associated with a reduced risk of death in patients with heart failure. Current
      evidence supports statin use in individuals with recognized heart failure and
      concomitant coronary heart disease, dyslipidemia, or diabetes mellitus. More data
      are needed before statins can be recommended in those with isolated heart
      failure.

PMID- 17495257
TI  - Transmyocardial revascularization: peril and potential.
AB  - Transmyocardial laser revascularization is a technique for the treatment of
      patients with chronic angina pectoris that is refractory to medical therapy and
      who are not eligible for surgical intervention. Percutaneous myocardial
      revascularization is a less-invasive catheter-based procedure that has been
      adapted from transmyocardial laser revascularization. Six prospective randomized
      clinical trials have been performed with transmyocardial laser revascularization
      and 5 have been performed using percutaneous myocardial revascularization. All of
      the transmyocardial laser revascularization and 4 of the percutaneous myocardial
      revascularization studies showed a significant improvement in angina class;
      however, results for improved survival, increased exercise tolerance, improved
      ejection fraction, and improved myocardial perfusion were less definitive.
      Transmyocardial laser revascularization has significant potential for morbidity
      and mortality. This article summarizes the results of the randomized trials,
      explains the current theories for the mechanism of transmyocardial laser
      revascularization, and discusses its current role in treatment for patients,
      considering the evidence that currently exists.

PMID- 17495256
TI  - Observations on the safety and effectiveness of dofetilide in patients with
      paroxysmal atrial fibrillation and normal left ventricular function.
AB  - Dofetilide is currently recommended as second-tier therapy to maintain sinus
      rhythm in patients with paroxysmal atrial fibrillation (PAF) and normal left
      ventricular function, yet limited data support this recommendation. We examined
      the safety and efficacy of dofetilide in this setting through a retrospective
      chart review. We evaluated patients who had symptomatic PAF, normal left
      ventricular function, and no significant valvular disease. The end points were
      complete suppression of symptomatic PAF and subjective symptomatic improvement
      with dofetilide treatment. Over a 3-year period, 34 patients who had failed
      previous antiarrhythmic therapy were included. Of these, 3 discontinued
      dofetilide treatment before discharge. Of the remaining 31 who continued
      treatment after discharge, it was eventually discontinued in 13. At 12 months,
      symptomatic improvement was observed in 18 of 31 patients, 6 of whom remained
      asymptomatic. Treatment with dofetilide in this study was successful in less than
      1 in 5 patients. Despite careful precautions, serious proarrhythmias, the major
      limiting side effect of dofetilide, still occurred during long-term follow-up.

PMID- 17495258
TI  - Preoperative platelet inhibition with eptifibatide during coronary artery bypass
      grafting with cardiopulmonary bypass.
AB  - Platelet glycoprotein IIb-IIIa antagonists reduce cardiac events in acute
      coronary syndromes (ACSs), but their use is limited during coronary artery bypass
      grafting (CABG) because of bleeding concerns. Patients with ACS, however, are at
      increased risk for cardiac events after CABG. The use of short-acting
      glycoprotein IIbIIIa inhibitor eptifibatide in patients with ACS undergoing CABG
      was investigated. Fifteen patients with ACS and undergoing CABG with
      cardiopulmonary bypass were enrolled. One withdrew before surgery. Patients
      received heparin and eptifibatide preoperatively. Eptifibatide concentration and
      receptor occupancy (RO) at termination of infusion were similar in the two
      groups. Immediately before surgery, eptifibatide levels in the 2-hour group were
      twice that in the 4-hour group, and platelet RO was higher. Cessation of
      eptifibatide 4 hours before surgery results in less bleeding and transfusions
      than 2 hours before surgery. The optimal balance between bleeding and platelet
      inhibition is approximately 60% platelet RO. Further investigation of upstream
      therapy should target this threshold.

PMID- 17495259
TI  - Short-term intra-arterial infusion of monocyte chemoattractant protein-1 results
      in sustained collateral artery growth.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a stimulator of collateral artery
      growth and has been shown to increase collateral artery conductance in rabbits
      and pigs. The minimal infusion duration and the minimally effective dose of MCP-1
      are currently unknown, as is the sustainability of the therapeutic effect over a
      longer observation period than tested before. MCP-1 was infused intra-arterially
      in pigs after unilateral femoral artery occlusion in different doses and infusion
      durations between 2 hours and 2 weeks. Two weeks after ligation, arterial
      conductance under maximal vasodilatation was measured. The long-term efficacy was
      investigated in 2 additional groups of animals after 6 weeks. Infusion with 2
      microg/min of MCP-1 for 6 hours was sufficient to double arterial conductance,
      and arterial conductance after 6 weeks was still significantly increased.

PMID- 17495260
TI  - Effects of rotigaptide, a gap junction modifier, on defibrillation energy and
      resuscitation from cardiac arrest in rabbits.
AB  - The gap junction modifier Rotigaptide (ZP123), which promotes cellular coupling,
      was hypothesized to decrease defibrillation thresholds during prolonged
      ventricular fibrillation (VF). Thirty-two New Zealand white rabbits were
      randomized to receive saline (control, n = 16) or Rotigaptide (n = 16). Following
      4 min of untreated VF, biphasic defibrillation shocks were applied through chest
      wall patches, starting either at 300 volts (V) (n = 16) or 500 V (n = 16), with
      200 V increasing steps to 900 V in case of shock failure. Rotigaptide
      significantly decreased defibrillation voltage requirements (average cumulative
      voltage of all shocks: 1206 +/- 709 V in control group vs. 844 +/- 546 V in
      treated group, P = .002). Rotigaptide had no effect on heart rate, QRS duration,
      QT interval, ventricular effective refractory period, monophasic action potential
      duration or on connexin 43 density using immunofluorescence. Rotigaptide improves
      the ability to defibrillate after untreated VF.

PMID- 17495261
TI  - Effect of coronary angiography on oxidative DNA damage observed in circulating
      lymphocytes.
AB  - Endogenous oxidative DNA damage is caused by multiple endogenous and exogenous
      factors. It is not completely known whether coronary angiography has an effect on
      DNA damage. The aim of this study was to investigate whether coronary angiography
      causes oxidative DNA damage. Fifty-four patients who underwent elective coronary
      angiography for diagnostic purpose were enrolled to the study. For each subject,
      the frequency of oxidative DNA damage was analyzed by using the comet assay,
      which is a sensitive biomarker of DNA damage, before and after diagnostic
      procedures. A highly significant increase of DNA damage mean score was observed
      in all patients after the coronary angiography procedure (p < 0.001). No
      significant associations were found between the change in oxidative DNA damage
      and dose of contrast media and radiation exposure time. A significant correlation
      was observed between the change of DNA damage and age, hyperlipidemia,
      hypertension, smoking, Gensini score index, and vitamin B(12) (r = 0.496, p<
      0.001 ; r = 0.416, p = 0.002; r = 0.284, p = 0.038; r = 0.275, p = 0.044; r =
      0.742, p < 0.001; r = -0.347, p = 0.048, respectively). The change of oxidative
      DNA damage was higher in patients with 3-vessel disease compared with 2-vessel
      disease, 1-vessel disease, and normal coronary arteries (99.6 +/-8.4, 62.0 +/
      2.0, 43.2 +/-8.4, 21.6 +/-11.6 respectively; ANOVA p < 0.001). Multiple linear
      regression analysis showed that age and Gensini score index were independent
      predictors of the change of DNA damage (beta = 0.425, p = 0.003, beta = 0.684, p
      = 0.001 respectively). Our findings demonstrate that increased oxidative DNA
      damage in undergoing coronary angiography might be dependent on the severity of
      coronary artery disease and age, rather than on contrast media and radiation
      exposure time.

PMID- 17495262
TI  - Role of novel biomarkers of inflammation in patients with stable coronary heart
      disease.
AB  - Atherosclerosis is a dynamic chronic inflammatory process, and some inflammatory
      biomarkers have roles in this process. The levels of C-reactive protein (CRP) in
      patients with chronic stable coronary heart disease (CHD) have not been
      investigated well, and the levels of macrophage colony-stimulating factor (M-CSF)
      and interleukin-3 (IL-3) in patients with chronic stable CHD and the effects of
      these cytokines on atherogenesis are not known. To determine whether new
      inflammatory biomarkers have roles in atherosclerosis, the authors measured the
      levels of CRP, M-CSF, and IL-3 in patients with chronic stable CHD and in healthy
      controls. They measured plasma CRP concentrations by using a highly sensitive CRP
      reagent with immunonephelometric method, and plasma M-CSF and IL-3 concentrations
      with the help of a commercial enzyme-linked immunoassay test in 31 patients with
      chronic stable CHD documented by coronary angiography and in 22 age-matched
      healthy control subjects documented by coronary angiography. Mean plasma CRP, M
      CSF, and IL-3 concentrations in patients with chronic stable CHD were
      significantly higher than those in controls (8.2 vs 4.6 mg/L, 195.3 vs 28.9
      pg/mL, 173 vs 118 ng/mL, respectively, ppi.05). CRP, M-CSF, and IL-3 were all
      increased in patients with chronic stable CHD relative to controls. These
      findings suggest that these are new inflammatory biomarkers that may have
      important roles in the development of atherosclerotic lesions.

PMID- 17495263
TI  - Coronary artery spasm-related acute coronary syndrome in patients with coexisting
      spasm of angiographically normal coronary artery and fixed narrowing of the
      remaining vessels.
AB  - Fourteen patients with acute coronary syndrome are presented in this study.
      During angiography, hemodynamically significant coronary artery disease was
      demonstrated; however, it was not consistent with the electrocardiographic
      findings. The coronary artery spasm could be provoked in the rest of the
      angiographically normal coronary artery. Patient chest pain disappeared after
      administration of calcium channel blockers and/or isosorbide dinitrite. It is
      suggested that (1) both coronary artery spasm with no fixed stenosis and coronary
      atherosclerosis with fixed coronary stenosis can coexist in the same patient and
      cause symptoms, and (2) it is important to identify the predominant cause of
      symptoms, which then guides correct management.

PMID- 17495264
TI  - Defective adrenergic responses in patients with arsenic-induced peripheral
      vascular disease.
AB  - Blackfoot disease is an endemic arsenic-induced peripheral vascular disease in
      southern Taiwan. The main pathologic feature is atherosclerosis, which may relate
      to imbalances of the adrenergic system. The purpose of this study is to
      investigate the peripheral adrenergic responses of patients with blackfoot
      disease. Eight patients with blackfoot disease and four age-matched healthy
      controls were enrolled in this study. Baseline cutaneous perfusion was measured
      with a laser Doppler flowmeter. The response of alpha-adrenoceptors in the
      cutaneous microcirculation was assessed with laser Doppler flowmetry with
      iontophoresis of phenylephrine into the nailfold. In vitro binding with (125)I
      cyanopindolol determined beta-adrenoceptor density in lymphocytes. The cyclic
      adenosine monophosphate (cAMP) level at baseline and after isoproterenol
      stimulation reflects lymphocyte beta-adrenergic responsiveness. Results revealed
      persistently decreased skin perfusion in patients with blackfoot disease. In
      contrast, there was a transient decrease in skin perfusion in healthy controls
      after iontophoresis of phenylephrine. Both beta-2 receptor density and
      isoproterenol-stimulated cAMP levels in lymphocytes decreased. Increased
      peripheral alpha-adrenergic response and decreased beta-2-adrenergic response are
      related to increased vascular tone and result in atherosclerosis. Our findings of
      accentuated alpha-adrenergic response in microcirculation and decreased
      lymphocyte beta-2-adrenoceptor response play an important role in the
      pathogenesis of atherosclerosis in blackfoot disease.

PMID- 17495265
TI  - Platelet receptor HPA-1 polymorphism of alphaIIbbeta3 and 807 C/T polymorphism of
      alpha2beta1 and Buerger's disease.
AB  - Thromboangiitis obliterans or Buerger's disease is an episodic and segmental
      inflammatory and thrombotic process of the medium and small arteries of the lower
      extremities. Even though the disease was described 90 years ago, the
      etiopathogenesis is still under consideration. Afflicted patients are mostly
      young male cigarette smokers without signs of atherosclerosis or other risk
      factors for peripheral arterial occlusive disease. This indicates that hereditary
      thrombophilic factors could play a role in the etiopathogenesis. Recently,
      increasing evidence shows that platelet receptor polymorphisms (HPA-1
      polymorphism of beta3 subunit of alphaIIbbeta3 and 807 C/T polymorphism
      alpha2beta1) are associated with early onset of arterial thrombosis (myocardial
      infarction, stroke). This case-control study was designed to assess whether the
      807 C/T polymorphism or the HPA-1 polymorphism is involved in the pathogenesis of
      Buerger's disease or has any influence on the clinical course of Buerger's
      disease. Eighteen patients with Buerger's disease and 81 (sex and age matched)
      healthy control subjects (mean age 44 +/- 10 vs 45 +/- 8 years, respectively)
      were genotyped for platelet receptor HPA-1 and GPIa 807 C/T polymorphism. The
      gene frequency of HPA-1 and GPIa 807 C/T polymorphisms was identical in both
      groups. Prevalence of hetero- and homozygous carriers of the HPA-1b allel (1a1b
      and 1b1b genotype) as well as the prevalence of the 807 C/T and 807 T/T carriers
      did not differ significantly between the two groups, p >0.05. The grade of
      clinical disease manifestation as well as disease progression did not reveal any
      significant relationship with HPA-1 and 807 C/T polymorphisms. A relationship
      between the age at onset of the disease and HPA-1 polymorphism was not found.
      Otherwise analysis of the GPIa 807 C/T platelet receptor polymorphism showed that
      the average age of patients who are carriers of the T allele at early onset of
      disease was 32 +/- 6 years (range 27-48 years) compared to 42 +/- 6 years (range
      34-53 years) of the C/C carriers (p <0.05). This indicates that the GPIa 807 C/T
      polymorphism does not represent a risk factor for Buerger's disease itself, but
      could be associated with premature onset of this disorder in predisposed
      individuals.

PMID- 17495266
TI  - Reduced arterial circulation to the legs in spinal cord injury as a cause of skin
      breakdown lesions.
AB  - Skin breakdown lesions (SBLs) of the legs are common in spinal cord injury (SCI).
      It is assumed that the cause is deficient sensitivity and immobility of the
      limbs, which result in areas subjected to prolonged pressures. However, poor
      circulation may also be a significant factor. Indeed, strong reasons suggest that
      small vessel circulation is decreased in SCI because these patients have
      increased arteriosclerotic risk factors. Patients in the SCI population have
      advanced age, are sedentary, often have abnormal carbohydrate and lipid
      metabolism, and many use tobacco products. Total blood flow (TBF) to the legs and
      skin blood flows (SBFs) to 4 areas of the feet were measured simultaneously by
      duplex Doppler sonography and laser Doppler flowmetry in 10 healthy control and
      10 chronic subjects with SCI when supine and during 30 minutes in a wheelchair.
      The average supine control TBF was 540 mL/minute, but greatly reduced between 24
      76 mL/minute in 4 of the subjects. During sitting, the average TBF fell by 41% in
      the controls and increased by 6% in SCI. Nonetheless, in all control and SCI
      subjects the average sitting SBFs were severely decreased in all areas between 53
      75%, similar to results found by others elsewhere in the foreleg. Ischemia of the
      skin and underlying muscles is important as a cause for the poor healing of SBLs
      in persons with SCI who daily spend many hours in a wheelchair.

PMID- 17495267
TI  - Impact of enhanced external counterpulsation on peripheral circulation.
AB  - Enhanced external counterpulsation (EECP) is a noninvasive counterpulsation
      technique that reduces angina and improves exercise capacity in patients with
      coronary artery disease. Diastolic coronary perfusion is augmented by pneumatic
      compression of 3 sets of cuffs wrapped around the lower extremities. Although
      central hemodynamic changes are well investigated, almost no data exist about the
      changes of peripheral circulation during EECP. In this study, 12 patients with
      angina and angiographic evidence of coronary artery disease were treated for 1
      hour with EECP. In these patients, peripheral artery disease was excluded by
      duplex sonography. The patients rested 1 hour before EECP in supine position, and
      they remained in that position for 1 hour after the procedure. Changes of flow
      volumes and flow pattern of the posterior tibial artery and the brachial artery
      were measured by sonography at the end of all 3 periods. Furthermore, we measured
      the concentration of circulating prostanoids at these 3 time points. Averaged
      flow volume of the posterior tibial artery decreased to 69% +/- 23% (P < .05)
      during EECP and increased to 133% +/- 34% (P < .05) of baseline 1 hour after the
      procedure. In contrast, the averaged flow volume of the brachial artery increased
      by 9% +/- 4% (P < .05) during EECP and returned to baseline values after EECP.
      The flow pattern of the posterior tibial artery showed a second early diastolic
      antegrade flow caused by the cuff inflation and a reverse end-diastolic flow
      after the deflation of the cuffs. These flow changes caused an increase of the
      pulsatility index by Gosling (397% during EECP), returning to baseline values in
      the recovery period. Plasma concentrations of circulating prostanoids showed no
      significant change during EECP. Thus, pedal flow volume decreased to
      approximately two thirds of baseline during EECP followed by reactive hyperemia
      even 1 hour after the procedure; however, this decreased perfusion triggered no
      change of the prostacyclin/thromboxane ratio and was well tolerated by all
      investigated patients. The observed 4-fold increase of the peripheral pulsatility
      index supports the thesis of increase of shear-stress-related improvement of
      endothelial function during EECP.

PMID- 17495268
TI  - Abdominal aortic aneurysm or aortic occlusive disease: role of trace element
      imbalance.
AB  - The nature of the relationship between atheromatous disease and degenerative
      aneurysm is yet to be defined. The purpose of this study was to compare tissue
      Fe, Cu, Zn, and thiobarbituric acid reactive substances (TBARS) levels (as a
      marker of lipid peroxidation) in the abdominal aorta in relation to the
      development of aneurysmal and occlusive disease in the infrarenal aorta. This was
      a prospective clinical study in an institutional referral center, in hospitalized
      patients. Eighty male patients who underwent surgery for abdominal aortic
      aneurysm (AAA) or aortic occlusive disease (AOD) were included in the study. Age,
      risk factors and comorbid conditions were recorded, including diabetes mellitus,
      hypertension, coronary artery disease, smoking, and chronic obstructive pulmonary
      disease. Aortic wall biopsies were collected at operation from the anterolateral
      section of the infrarenal aorta. Tissue Fe, Cu, Zn, and TBARS levels were
      determined. The mean age of the AAA group was 66.2 (56-75) years and of the AOD
      group 57.8 (47-72) years (p <0.001). There was a higher prevalence of
      hypertension in AAA patients compared to AOD patients (62.5%, 35% respectively; p
      <0.05). The comparison of tissue Zn levels showed no significant difference.
      Tissue levels of Fe, Cu, and TBARS were found to be higher in the AAA group,
      compared with the AOD group (p<0.001 for each). These results suggest that higher
      oxidative stress as a result of higher Fe and Cu levels in the AAA, compared with
      AOD, may be one of the contributing factors in aneurysmal formation as a result
      of promoted wall erosion.

PMID- 17495269
TI  - Afterload reduction may halt and beta-adrenergic blockade may worsen progression
      of left ventricular dysfunction in patients with chronic compensated mitral
      regurgitation: a retrospective cohort study.
AB  - Severe chronic mitral regurgitation (MR) is associated with progressive left
      ventricular (LV) systolic dysfunction. Both afterload reduction and beta
      adrenergic blockade have been suggested as methods for preventing LV dysfunction
      in asymptomatic patients with MR and normal LV function, who are therefore not
      yet candidates for surgical intervention. The objective of this study was to
      determine if afterload reduction reduces progression of LV dysfunction in
      patients with severe MR. The reports of echocardiographic studies performed 20 +/
      14 months apart were compared in a retrospective cohort of 134 asymptomatic
      patients with moderate-severe chronic MR and baseline ejection fraction (LVEF)
      >50%. Groups were defined by exposure to any afterload-reducing drug: Group 0, no
      exposure; Group 1, exposure beginning after the first echocardiogram; and Group
      2, drug exposure beginning before the baseline echocardiogram. The groups
      differed importantly only in treatment duration. In 72 patients not exposed to
      beta-adrenergic blockade, LVEF decreased by a relative -3.2% in Group 0, while
      Group 1 increased by 3.4% and Group 2 increased by 5.1%, p <0.01. Among 62
      patients exposed to beta-adrenergic blockade, LVEF consistently worsened (Group
      0, 4.8%; Group 1, -3.3%; Group 2, -1.7%; p = 0.71) compared to the 72 patients
      without beta-adrenergic blockade. In a multivariate model that included treatment
      duration and exposure to other medications, the beneficial effect of afterload
      reduction (p <0.03) and the deleterious effect of beta-adrenergic blockade (p <
      0.02) were significant. Afterload reduction halted or reversed the progressive
      worsening of left ventricular function while beta-adrenergic blockade had a
      deleterious effect.

PMID- 17495270
TI  - Success, safety, and efficacy of implantation of diamond-like carbon-coated
      stents.
AB  - The aim of this study was to evaluate safety and clinically defined efficacy of
      the implantation of a new stent coated with diamond-like carbon (DLC stent), in a
      group of patients who underwent percutaneous transluminal coronary
      revascularization procedures in two hemodynamic centers. This study was an
      observational prospective nonrandomized study that included 196 patients with a
      total of 236 significant de novo atheromatous coronary lesions, in which 245 DLC
      stents were implanted. The primary end point of this study was a composite of
      major cardiovascular events (death or acute myocardial infarction with or without
      Q) and need for target lesion revascularization (TLR) or target vessel
      revascularization (TVR) procedure during the first 48 hours and at 6 months after
      the DLC stent implantation. All patients had a myocardial perfusion imaging study
      with Tl(201) at 6 months after DLC stent implantation. Only patients with a
      myocardial perfusion imaging study indicative of myocardial ischemia were then
      submitted for a new coronary angiogram. No major cardiovascular event or
      emergency TVR occurred during hospitalization. At 6-month follow-up no major
      cardiovascular event occurred either, whereas the rate for TLR was 5.6% and that
      for TVR was 7.65%. This preliminary study provides enough clinical evidence that
      implantation of intracoronary bare metal stents coated with diamond-like carbon
      is associated with high success rates, safety, and efficacy, both in the hospital
      and at the 6-month follow-up after the interventional procedure.

PMID- 17495271
TI  - The effects of acute passive smoke exposure on endothelium-dependent brachial
      artery dilation in healthy individuals.
AB  - Passive smoking has both short-term and long-term vascular effects. It is not
      clear whether impairment of endothelial function reflects the acute effects of
      passive smoke exposure or the chronic effects. The purpose of this study was to
      assess the hypothesis that short-term exposure to passive smoke impairs
      endothelium-dependent vasodilation in healthy nonsmokers. Eighteen healthy young
      never smokers (12 men, 6 women) 21 to 55 years old (mean +/- SD: 34 +/-9 years)
      underwent ultrasonography measuring baseline brachial-artery diameter and
      brachial-artery diameter during hyperemia and after sublingual administration of
      nitroglycerin, twice: in a smoke-free environment, and then in the same
      environment polluted by 30 to 35 ppm carbon monoxide. Each subject served as
      his/her control. Carboxyhemoglobin was measured in blood samples of subjects
      tested. Mean value of carboxyhemoglobin was 0.6 +/-0.5% in a smoke-free
      environment and 1.4 +/- 0.5% in a smoking environment (p <0.02). Mean values of
      flow-mediated dilation (FMD) were 12.6% +/- 7.8% in a smoke-free environment
      versus 6.8 +/- 7.8% in a smoking environment (p <0.01). On the contrary,
      nitroglycerin-induced vasodilation did not show any statistical difference (21 +/
      9.8% versus 23 +/-1.4%). Finally, the increase of carboxyhemoglobin was related
      statistically to the impairment of flow-mediated dilation (r = 0.51; p <0.002).
      Passive smoking impaired flow-mediated vasodilation in healthy never smokers in a
      smoking environment. The impairment was strongly related to carboxyhemoglobin
      level.

PMID- 17495272
TI  - QT interval analysis in patients with chronic liver disease: a prospective study.
AB  - In previous studies, it has been shown that QT interval prolongation is related
      to an increased mortality rate in chronic liver disease (CLD). But QT dispersion
      (QTd) and its clinical significance in CLD has not been well studied. The
      objectives of this study were to investigate the relation between QTd and
      severity of the disease and determine its prognostic value in cirrhotic patients.
      Thirty-three consecutive patients with cirrhosis and 35 sex- and age-matched
      healthy subjects were studied. QT intervals and QT dispersions were measured on
      admission, and all intervals were corrected for heart rate according to Bazett's
      formula. The authors analyzed the potential relationship between QT parameters
      and the disease severity according to Child-Pugh classification and compared
      these values between survivors and nonsurvivors after a 3-year follow-up. Child
      Pugh classification is used to assess liver function in cirrhosis. Corrected QT
      (QTc) prolongations were found in 32% of patients with cirrhosis and 5.7% of the
      healthy controls (p <0.001). The prevalence of increased (>70 ms) corrected QT
      dispersion (QTcd) was 45% in patients with cirrhosis. According to Child-Pugh
      criteria: QTd, maximum QT interval (QTmax), corrected QTmax (QTcmax), and QTcd in
      class C were significantly higher than those of class A and B (p <0.05, for all
      comparison). But there was no significant difference between class A and B in
      QTmax, QTcmax, QTd, and QTcd. There were 10 (30%) deaths from all causes during 3
      year follow-up in the study group. Cox regression analysis showed that QTd and
      QTcd were better mortality indicators than QTmax and QTcmax, and Child's
      classification was the best predictor for mortality among all variables. In
      conclusion, QT dispersion and corrected QT dispersion parameters were better
      mortality indicators than other QT interval parameters and also may give
      additional prognostic information in patients with chronic liver disease.

PMID- 17495273
TI  - Diet, exercise, and C-reactive protein levels in people with abdominal obesity:
      the ATTICA epidemiological study.
AB  - We evaluated the association of physical activity and diet with C-reactive
      protein (CRP) levels among subjects with abdominal obesity. During 2001-2002, we
      enrolled 625 men (18 to 87 years old) and 712 women (18 to 89 years old) with
      abdominal obesity (waist-to-hip ratio > or =0.95 in men and > or =0.8 in women)
      from the Attica area, Greece. The sampling was stratified by the age-gender
      distribution of the region (census 2001). Among several variables, we also
      measured plasma high-sensitivity CRP, physical activity status, dietary habits,
      blood lipids, and blood pressure levels. Adherence to the Mediterranean diet was
      evaluated through a diet score (0 to 55) that assessed the inherent
      characteristics of the diet. Compared with those with low CRP levels, subjects
      with high CRP levels (ie, >3.0 mg/L) were physically inactive (P = .01), were
      less likely to adopt the Mediterranean diet (P = .008), had higher glucose
      levels, had a higher prevalence of hypertension, had a lower high-density
      lipoprotein cholesterol, and had increased smoking habits and higher
      anthropometric indices (all P < .05). Moreover, adoption of the Mediterranean
      diet in combination with medium physical activity seems to reduce the likelihood
      of having high CRP levels by 72% (P = .018), irrespective of smoking and various
      clinical and biological characteristics. Among subjects with abdominal obesity,
      low-grade systemic inflammation appears to be associated with the adoption of an
      unfavorable lifestyle, including physical inactivity and unhealthy dietary
      habits, as well as increased blood pressure levels and low high-density
      lipoprotein cholesterol.

PMID- 17495274
TI  - Bilateral lower extremity gangrene requiring amputation associated with heparin
      induced thrombocytopenia: a case report.
AB  - Heparin is a common cause of thrombocytopenia in hospitalized patients. Between
      10% and 15% of patients receiving therapeutic doses of heparin develop
      thrombocytopenia. Heparin-induced thrombocytopenia (HIT) can cause severe
      bleeding and thrombosis owing to intravascular platelet aggregation. HIT must be
      distinguished from other causes of thrombocytopenia. Importantly, heparin use is
      often associated with an early fall in the platelet count that usually occurs
      within the first 4 days of initiation and recovers without cessation of heparin
      treatment. This nonimmune heparin-associated thrombocytopenia has not been found
      to be associated with thrombosis and does not necessitate discontinuation of
      heparin. The authors present a case report of a 70-year-old man who received
      heparin therapy following aortic tissue valve replacement and aortic root repair
      with graft and developed bilateral lower extremity arterial clots 6 days
      postoperatively in the setting of positive heparin antibody titers. Ultimately
      the patient required bilateral above-knee amputations.

PMID- 17495275
TI  - Heart failure in systemic lupus erythematosus treated by cardiac
      resynchronization: a case report.
AB  - The presented case report describes a female patient suffering from systemic
      lupus erythematosus, in whom dilated cardiomyopathy with progressive heart
      failure was a very first symptom of the disease. The advanced invasive treatment
      method, cardiac resynchronization therapy, was successfully applied to improve
      the quality of life, clinical symptoms, and exercise tolerance.

PMID- 17495276
TI  - Coronary-subclavian steal: case series and review of diagnostic and therapeutic
      strategies: three case reports.
AB  - Due to the increased use of internal mammary artery grafts for coronary
      revascularization, proximal subclavian stenosis resulting in coronary-subclavian
      steal has become an important clinical entity. Patients present with varying
      signs and symptoms of recurrent myocardial ischemia that not only can limit
      lifestyle but also be life-threatening. A careful history and physical
      examination with the identification of risk factors such as peripheral vascular
      disease and arm blood pressure differential >20 mm Hg can identify patents at
      high risk for developing this syndrome. Identifying these patients before
      coronary artery bypass grafting can prevent this important problem by altering
      the therapeutic approach to coronary revascularization. When patients present
      after coronary artery bypass grafting with coronary-subclavian steal, therapeutic
      options of percutaneous transluminal angioplasty and stent placement to the
      subclavian artery, carotid-subclavian bypass, and axillary-axillary bypass all
      have high success rates with excellent long-term patency rates. The choice for
      the type of revascularization needs to be individualized based on the lesion
      morphology and clinical comorbidities. Three patients who presented with signs
      and symptoms of myocardial ischemia due to coronary subclavian steal are
      presented. All 3 patients had incapacitating symptoms, and all 3 were treated
      successfully with different revascularization techniques due to other medical
      conditions or comorbidities.

PMID- 17495277
TI  - An unusual case of renal artery stent restenosis: a case report.
AB  - The authors report a case of renal artery stent restenosis exacerbated by the
      likely displacement of multiple bare metal stents that had been contiguously
      deployed 3 months previously. The unusual features of this case are discussed
      along with putative mechanisms of stent displacement in visceral arteries. The
      restenotic disease was successfully treated with excimer laser atherectomy and
      cutting balloon atherotomy.

PMID- 17495278
TI  - Intracavitary mass as the initial manifestation of primary pericardial
      mesothelioma: a case report.
AB  - A 31-year-old woman presented with a 3-month history of progressing fatigue and
      effort dyspnea. Echocardiography depicted a tumor within the free wall of the
      right ventricle and right atrium, located on both sides of the tricuspid annulus.
      Computed tomography showed disseminated circular shadows sized up to 7 mm--most
      likely metastatic lesions--in both lungs. The diagnosis of low-grade mesothelioma
      bifasicum was confirmed with histopathologic and immunohistochemical studies of
      the samples taken by thoracoscopy from parietal pleura, lung tumor, and diaphragm
      region. Chemotherapy, which included gemcitabine and carboplatin, resulted in
      transient improvement of the clinical status of the patient and reduction of the
      tumor mass lasting several months followed by progression of the disease.
      Significant amounts of pleural fluid and huge tumors within both pleural cavities
      emerged. The patient died due to respiratory and circulatory insufficiency 11
      months following the diagnosis.

PMID- 17495279
TI  - The effects of food on the pharmacokinetics of a formulated ACP-103 tablet in
      healthy volunteers.

PMID- 17495280
TI  - Tolerability, pharmacokinetics, and neuroendocrine effects of PRX-00023, a novel
      5-HT1A agonist, in healthy subjects.
AB  - PRX-00023 is a novel, nonazapirone 5-HT1A agonist in clinical development for
      treatment of affective disorders. The objectives of the initial clinical phase I
      studies (a single ascending dose study and multiple dose-ascending and high-dose
      titration studies) were to measure the pharmacokinetics, pharmacodynamic
      (neuroendocrine) effects, and tolerability of PRX-00023 in healthy subjects. The
      studies evaluated 10-mg to 150-mg doses of PRX-00023 in up to 112 healthy male
      and female subjects aged 18 to 54 years. Single and multiple oral doses of PRX
      00023 were found to be safe and well tolerated in healthy subjects. PRX-00023 was
      absorbed relatively rapidly, with a tmax of 0.5 to 2 hours, and eliminated with a
      half-life of approximately 12 hours. PRX-00023 treatment transiently increased
      blood prolactin levels 2 to 3 hours after administration, consistent with its
      mechanism as a 5-HT1A agonist.

PMID- 17495281
TI  - What every radiologist should know about idiopathic interstitial pneumonias.
AB  - The American Thoracic Society-European Respiratory Society classification of
      idiopathic interstitial pneumonias (IIPs), published in 2002, defines the
      morphologic patterns on which clinical-radiologic-pathologic diagnosis of IIPs is
      based. IIPs include seven entities: idiopathic pulmonary fibrosis, which is
      characterized by the morphologic pattern of usual interstitial pneumonia (UIP);
      nonspecific interstitial pneumonia (NSIP); cryptogenic organizing pneumonia
      (COP); respiratory bronchiolitis-associated interstitial lung disease (RB-ILD);
      desquamative interstitial pneumonia (DIP); lymphoid interstitial pneumonia (LIP);
      and acute interstitial pneumonia (AIP). The characteristic computed tomographic
      findings in UIP are predominantly basal and peripheral reticular opacities with
      honeycombing and traction bronchiectasis. In NSIP, basal ground-glass opacities
      tend to predominate over reticular opacities, with traction bronchiectasis only
      in advanced disease. COP is characterized by patchy peripheral or
      peribronchovascular consolidation. RB-ILD and DIP are smoking-related diseases
      characterized by centrilobular nodules and ground-glass opacities. LIP is
      characterized by ground-glass opacities, often in combination with cystic
      lesions. AIP manifests as diffuse lung consolidation with ground-glass opacities,
      which usually progress to fibrosis in patients who survive the acute phase of the
      disease. Correct diagnosis of IIPs can be achieved only by means of
      interdisciplinary consensus and stringent correlation of clinical, imaging, and
      pathologic findings. (c) RSNA, 2007.

PMID- 17495282
TI  - Eosinophilic lung diseases: a clinical, radiologic, and pathologic overview.
AB  - Eosinophilic lung diseases are a diverse group of pulmonary disorders associated
      with peripheral or tissue eosinophilia. They are classified as eosinophilic lung
      diseases of unknown cause (simple pulmonary eosinophilia [SPE], acute
      eosinophilic pneumonia [AEP], chronic eosinophilic pneumonia [CEP], idiopathic
      hypereosinophilic syndrome [IHS]), eosinophilic lung diseases of known cause
      (allergic bronchopulmonary aspergillosis [ABPA], bronchocentric granulomatosis
      [BG], parasitic infections, drug reactions), and eosinophilic vasculitis
      (allergic angiitis, granulomatosis [Churg-Strauss syndrome]). The percentages of
      eosinophils in peripheral blood and bronchoalveolar lavage fluid are essential
      parts of the evaluation. Chest computed tomography (CT) demonstrates a more
      characteristic pattern and distribution of parenchymal opacities than does
      conventional chest radiography. At CT, SPE and IHS are characterized by single or
      multiple nodules with a surrounding ground-glass-opacity halo, AEP mimics
      radiologically hydrostatic pulmonary edema, and CEP is characterized by
      nonsegmental airspace consolidations with peripheral predominance. ABPA manifests
      with bilateral central bronchiectasis with or without mucoid impaction. The CT
      manifestations of BG are nonspecific and consist of a focal mass or lobar
      consolidation with atelectasis. The most common CT findings in Churg-Strauss
      syndrome include sub-pleural consolidation with lobular distribution,
      centrilobular nodules, bronchial wall thickening, and interlobular septal
      thickening. The integration of clinical, radiologic, and pathologic findings
      facilitates the initial and differential diagnoses of various eosinophilic lung
      diseases.

PMID- 17495283
TI  - Imaging manifestations of blastomycosis: a pulmonary infection with potential
      dissemination.
AB  - Pulmonary blastomycosis is an uncommon pathologic condition that is endemic to
      Canada and the upper Midwest of the United States. Blastomycosis has a variety of
      radiologic manifestations, including airspace consolidation, focal masses,
      intermediate-sized nodules, interstitial disease, miliary disease, and cavitary
      lesions. Affected patients may be asymptomatic or may present with clinical
      manifestations ranging from mild chronic cough to acute respiratory distress
      syndrome-like symptoms. Patients with acute symptoms are more likely to have
      airspace consolidation, whereas chronic manifestations may be associated with
      masslike lesions. Intermediate-sized nodules with accompanying airspace
      consolidation, particularly in the upper lobes, should raise suspicion for fungal
      disease. Lymphadenopathy and pleural effusions are quite uncommon, and
      calcification is not often seen. Blastomycosis may be aggressive and require
      treatment. Dissemination from the lung is not unusual and can involve any organ.
      Diagnosis is often delayed because blastomycosis can mimic many other disease
      processes, including bacterial pneumonia, malignancy, and tuberculosis.
      Radiologists can best contribute to the care of patients who live or travel in
      endemic areas by maintaining a high degree of suspicion for blastomycosis and
      being familiar with its myriad manifestations.

PMID- 17495284
TI  - A diagnostic approach to mediastinal abnormalities.
AB  - A number of mediastinal reflections are visible at conventional radiography that
      represent points of contact between the mediastinum and adjacent lung. The
      presence or distortion of these reflections is the key to the detection and
      interpretation of mediastinal abnormalities. Anterior mediastinal masses can be
      identified when the hilum overlay sign is present and the posterior mediastinal
      lines are preserved. Widening of the right paratracheal stripe and convexity
      relative to the aortopulmonary window reflection indicate a middle mediastinal
      abnormality. Disruption of the azygoesophageal recess can result from disease in
      either the middle or posterior mediastinum. Paravertebral masses disrupt the
      paraspinal lines, and the location of masses above the level of the clavicles can
      be inferred by their lateral margins, which are sharp in posterior masses but not
      in anterior masses. The divisions of the mediastinum are not absolute; however,
      referring to the local anatomy of the mediastinal reflections in an attempt to
      more accurately localize an abnormality may help narrow the differential
      diagnosis. Identification of the involved mediastinal compartment helps determine
      which imaging modality might be appropriate for further study.

PMID- 17495285
TI  - Herbert Y. Kressel, MD, named editor of radiology.

PMID- 17495286
TI  - Advances in digital radiography: physical principles and system overview.
AB  - During the past two decades, digital radiography has supplanted screen-film
      radiography in many radiology departments. Today, manufacturers provide a variety
      of digital imaging solutions based on various detector and readout technologies.
      Digital detectors allow implementation of a fully digital picture archiving and
      communication system, in which images are stored digitally and are available
      anytime. Image distribution in hospitals can now be achieved electronically by
      means of web-based technology with no risk of losing images. Other advantages of
      digital radiography include higher patient throughput, increased dose efficiency,
      and the greater dynamic range of digital detectors with possible reduction of
      radiation exposure to the patient. The future of radiography will be digital, and
      it behooves radiologists to be familiar with the technical principles, image
      quality criteria, and radiation exposure issues associated with the various
      digital radiography systems that are currently available.

PMID- 17495287
TI  - Inferior phrenic artery: anatomy, variations, pathologic conditions, and
      interventional management.
AB  - The inferior phrenic artery (IPA) is the most common source of extra-hepatic
      collateral blood supply for hepatocellular carcinoma (HCC) and frequently
      supplies HCCs located in the bare area of the liver. Other pathologic conditions
      including hemoptysis, diaphragmatic or hepatic bleeding due to trauma or surgery,
      and bleeding caused by gastroesophageal problems (eg, Mallory-Weiss tear or
      gastroesophageal cancer) may be related to the IPA. Over a 4-year period, the
      authors performed 383 interventional procedures related to the IPA. The right and
      left IPAs originate with almost equal frequency from the aorta and celiac axis
      and with lesser frequency from the renal arteries. Various other sites of origin
      such as the left gastric, hepatic, superior mesenteric, spermatic, and adrenal
      arteries-are also seen. Radiologists must be familiar with the normal spectrum of
      IPA anatomy so that detection and adequate interventional management can be
      achieved when pathologic conditions related to the IPA are present.

PMID- 17495288
TI  - Greater and lesser omenta: normal anatomy and pathologic processes.
AB  - The peritoneum is the largest serous membrane in the body and the one with the
      most complex structure. The omentum is a double-layered extension of the
      peritoneum that connects the stomach to adjacent organs. The peritoneal
      reflections form the greater and lesser omenta, and the natural flow of
      peritoneal fluid determines the route of spread of intraperitoneal fluid and
      consequently of disease processes within the abdominal cavity. The omenta serve
      both as boundaries for disease processes and as conduits for disease spread. The
      omenta are frequently involved by infectious, inflammatory, neoplastic, vascular,
      and traumatic processes. Computed tomography (CT) is a primary diagnostic method
      for evaluation of omental diseases, most of which may manifest with nonspecific
      clinical features. Multidetector CT with multiplanar reformation allows accurate
      examination of the complex anatomy of the peritoneal cavity, knowledge of which
      is the key to understanding the pathologic processes affecting the greater and
      lesser omenta.

PMID- 17495289
TI  - MR imaging of acute right lower quadrant pain in pregnant and nonpregnant
      patients.
AB  - The use of magnetic resonance (MR) imaging in the evaluation of acute abdominal
      pain is increasing, particularly in those circumstances where computed tomography
      (CT) is not desirable (eg, pregnancy, allergy to iodinated contrast material).
      Although ultrasonography (US) is considered the imaging study of choice for
      evaluation of abdominal pain in pregnant patients, MR imaging is a valuable
      adjunct to US in evaluation of pregnant patients with acute right lower quadrant
      (RLQ) pain who have inconclusive US results. MR imaging is also frequently used
      in patients with renal failure, in whom the use of iodinated contrast material is
      contraindicated, as well as in cases where CT results are inconclusive. In
      patients with acute RLQ pain, the breadth of abnormalities visible at MR imaging
      is very broad, with pathologic conditions potentially originating from multiple
      organ systems, but most commonly from the gastrointestinal and genitourinary
      systems. MR imaging is an excellent imaging modality for evaluation of RLQ pain
      and should be strongly considered in those patients in whom use of iodinated
      contrast media or radiation is not desirable.

PMID- 17495291
TI  - American Board of Radiology Perspective on Maintenance of Certification: Part IV-
      Practice Quality Improvement for Diagnostic Radiology.

PMID- 17495290
TI  - Improved detection and characterization of adrenal disease with PET-CT.
AB  - Positron emission tomography (PET)-computed tomography (CT) combines
      complementary modalities, thereby providing useful structural and functional
      information for the detection and characterization of a variety of conditions
      affecting the adrenal gland. The coregistered information provided by PET-CT is
      often superior to that provided by CT or PET owing to a variety of pitfalls
      inherent in the use of either modality alone. In addition, PET-CT can prove
      invaluable in the differentiation between benign and malignant adrenal disease.
      However, this combined modality also has certain limitations. Benign entities
      such as lipid-poor adenomas may demonstrate increased uptake at 2-[fluorine
      18]fluoro-2-deoxy-d-glucose PET while being indeterminate at standard CT.
      Moreover, the combined information from PET-CT will not always obviate additional
      studies or biopsy. Nevertheless, radiologists and nuclear physicians should be
      familiar with the common as well as the atypical manifestations of adrenal
      disease at PET and CT. They should also be meticulous in the performance and
      interpretation of PET-CT, which is crucial for optimal diagnosis and treatment.

PMID- 17495292
TI  - Complications of spinal instrumentation.
AB  - Despite tremendous technical advances in spine surgery in recent decades,
      patients may experience residual or recurrent pain and other symptoms after such
      surgery. The standard history and physical examination have only limited utility
      for assessing the postoperative anatomy, and radiologists can play an important
      role in diagnosing complications and guiding postoperative care. To do so
      effectively, they must be familiar with the imaging features of successful and
      unsuccessful fusion, instrumentation fracture and loosening, complications due to
      faulty hardware placement, and postoperative infection. A basic knowledge of
      spinal biomechanics and common approaches to surgical instrumentation also may
      help radiologists anticipate and identify complications.

PMID- 17495293
TI  - Overcoming artifacts from metallic orthopedic implants at high-field-strength MR
      imaging and multi-detector CT.
AB  - At magnetic resonance (MR) imaging and multidetector computed tomography (CT),
      artifacts arising from metallic orthopedic hardware are an obstacle to obtaining
      optimal images. Although various techniques for reducing such artifacts have been
      developed and corroborated by previous researchers, a new era of more powerful MR
      imaging and multidetector CT modalities has renewed the importance of a
      systematic consideration of methods for artifact reduction. Knowledge of the
      factors that contribute to artifacts, of related theories, and of artifact
      reduction techniques has become mandatory for radiologists. Factors that affect
      artifacts on MR images include the composition of the metallic hardware, the
      orientation of the hardware in relation to the direction of the main magnetic
      field, the strength of the magnetic field, the pulse sequence type, and other MR
      imaging parameters (mainly voxel size, which is determined by the field of view,
      image matrix, section thickness, and echo train length). At multidetector CT, the
      factors that affect artifacts include the composition of the hardware,
      orientation of the hardware, acquisition parameters (peak voltage, tube charge,
      collimation, and acquired section thickness), and reconstruction parameters
      (reconstructed section thickness, reconstruction algorithm used, and whether an
      extended CT scale was used). A comparison of images obtained with different
      hardware and different acquisition and reconstruction parameters facilitates an
      understanding of methods for reducing or overcoming artifacts related to metallic
      implants.

PMID- 17495294
TI  - Pitfalls in MR image interpretation prompting referrals to an orthopedic oncology
      clinic.
AB  - Patients referred to the authors' hospital for evaluation on suspicion of a bone
      or soft-tissue malignancy frequently present to the Orthopaedic Oncology Clinic
      with magnetic resonance (MR) images that show typical features of nonmalignant or
      nonneoplastic entities. The purpose of this article is to review the benign
      entities that may be mistaken by the radiologist for a malignancy and thus lead
      to needless referral to an orthopedic oncologist. Normal hematopoietic marrow and
      marrow edema due to a stress reaction may mimic a neoplasm at MR imaging, but
      knowledge of the typical patterns and locations of these features allows an
      accurate radiologic interpretation. The MR imaging appearance of osteonecrosis,
      Paget disease, benign bone lesions, and rheumatologic conditions may be
      confusing; in such circumstances, radiographic findings may help formulate a
      correct diagnosis. Knowledge of the common locations and appearances of bursae
      and ganglia is necessary so that radiologists do not misinterpret these benign
      entities as soft-tissue sarcomas. Soft-tissue trauma and inflammation also may
      mimic tumors at MR imaging, but a familiarity with the imaging patterns of
      nonneoplastic change in muscle allows the avoidance of misinterpretation. The
      clinical history, as always, is an important component of proper diagnosis. The
      radiologist can be especially useful to both the clinician and the patient by
      recognizing entities that are highly unlikely to represent malignancy and by
      confidently reporting those entities as benign, thereby sparing the patient an
      unnecessary trip to the orthopedic oncologist.

PMID- 17495295
TI  - Pre- and postoperative evaluation of congenital heart disease in children and
      adults with 64-section CT.
AB  - Although echocardiography is the imaging method of choice for diagnostic,
      preoperative, and postoperative evaluation of congenital heart disease, computed
      tomography (CT) is a helpful complementary imaging modality, particularly for
      postoperative evaluation. A thorough understanding of the normal anatomy and the
      morphologic features of congenital heart diseases is a prerequisite for choosing
      the optimal CT technique and achieving an accurate diagnosis. Furthermore, a
      close collaboration with a cardiologist with special training and expertise in
      congenital heart diseases is required. A sequential segmental approach should be
      used in evaluating morphologic features, especially during the review of CT
      images obtained in patients with rare congenital cardiac defects and in
      postoperative adult patients. To accurately document and interpret the altered
      flow conditions in patients with congenital heart disease, knowledge of the wide
      spectrum of surgical procedures and familiarity with the dedicated protocols for
      performing 64-section CT are needed.

PMID- 17495296
TI  - US Features of thyroid malignancy: pearls and pitfalls.
AB  - Thyroid nodules are common and occur in up to 50% of the adult population;
      however, less than 7% of thyroid nodules are malignant. High-resolution
      ultrasonography (US) is commonly used to evaluate the thyroid gland, but US is
      frequently misperceived as unhelpful for identifying features that distinguish
      benign from malignant nodules. Microcalcifications are one of the most specific
      US findings of a thyroid malignancy. Other useful US features include a marked
      hypoechogenicity, irregular margins, and the absence of a hypoechoic halo around
      the nodule. Lymphadenopathy and local invasion of adjacent structures are highly
      specific features of thyroid malignancy but are less commonly seen. The number,
      size, and interval growth of nodules are nonspecific characteristics. Suspicious
      US features may be useful for selecting patients for fine-needle aspiration
      biopsy when incidental nodules are discovered and when multiple nodules are
      present. Common interpretative pitfalls that may lead to failure to recognize a
      malignancy include mistaking cystic or calcified nodal metastases for nodules in
      a multinodular thyroid, mistaking diffusely infiltrative thyroid carcinomas and
      multifocal carcinomas for benign disease, and failing to recognize
      microcalcifications in papillary thyroid cancer.

PMID- 17495297
TI  - From the Archives of the AFIP: pulmonary veno-occlusive disease and pulmonary
      capillary hemangiomatosis.
AB  - Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis
      (PCH) are two unusual idiopathic disorders that almost uniformly manifest to the
      clinician as pulmonary arterial hypertension (PAH). Impressive clinical signs and
      symptoms often obscure the true underlying capillary or postcapillary disorder,
      thus severely compromising timely and appropriately directed therapy. The
      hemodynamics of PVOD and PCH are the consequence of a widespread vascular
      obstructive process that originates in either the alveolar capillary bed (in
      cases of PCH) or the pulmonary venules and small veins (in PVOD). Since the
      earliest descriptions of PVOD and PCH, there has been a debate as to whether
      these are two distinct diseases or varied expressions of a single disorder. The
      cause of PVOD or PCH has not yet been identified, although there are several
      reported associations. Without curative lung or heart-lung transplantation,
      patients with these conditions face inexorable clinical deterioration and death
      within months to a few short years of initial presentation. Surgical lung biopsy
      is the definitive diagnostic test, but it is a risky undertaking in such
      critically ill patients. The imaging manifestations of PVOD and PCH often reflect
      the underlying hemodynamic derangements, and these findings may assist the
      clinician in discerning PAH from an underlying capillary or postcapillary process
      with findings of septal lines, characteristic ground-glass opacities, and
      occasionally pleural effusion.

PMID- 17495298
TI  - Best cases from the AFIP: glioblastoma multiforme.

PMID- 17495299
TI  - Informatics in radiology: GridCAD: grid-based computer-aided detection system.
AB  - Grid computing-the use of a distributed network of electronic resources to
      cooperatively perform subsets of computationally intensive tasks-may help improve
      the speed and accuracy of radiologic image interpretation by enabling
      collaborative computer-based and human readings. GridCAD, a software application
      developed by using the National Cancer Institute Cancer Biomedical Informatics
      Grid architecture, implements the fundamental elements of grid computing and
      demonstrates the potential benefits of grid technology for medical imaging. It
      allows users to query local and remote image databases, view images, and
      simultaneously run multiple computer-assisted detection (CAD) algorithms on the
      images selected. The prototype CAD systems that are incorporated in the software
      application are designed for the detection of lung nodules on thoracic computed
      tomographic images. GridCAD displays the original full-resolution images with an
      overlay of nodule candidates detected by the CAD algorithms, by human observers,
      or by a combination of both types of readers. With an underlying framework that
      is computer platform independent and scalable to the task, the software
      application can support local and long-distance collaboration in both research
      and clinical practice through the efficient, secure, and reliable sharing of
      resources for image data mining, analysis, and archiving.

PMID- 17495301
TI  - Tree swallows (Tachycineta bicolor) nesting on wetlands impacted by oil sands
      mining are highly parasitized by the bird blow fly Protocalliphora spp.
AB  - Oil sands mining is steadily expanding in Alberta, Canada. Major companies are
      planning reclamation strategies for mine tailings, in which wetlands will be used
      for the bioremediation of water and sediments contaminated with polycyclic
      aromatic hydrocarbons and naphthenic acids during the extraction process. A
      series of experimental wetlands were built on companies' leases to assess the
      feasibility of this approach, and tree swallows (Tachycineta bicolor) were
      designated as upper trophic biological sentinels. From May to July 2004,
      prevalence and intensity of infestation with bird blow flies Protocalliphora spp.
      (Diptera: Calliphoridae) were measured in nests on oil sands reclaimed wetlands
      and compared with those on a reference site. Nestling growth and survival also
      were monitored. Prevalence of infestation was surprisingly high for a small
      cavity nester; 100% of the 38 nests examined were infested. Nests on wetlands
      containing oil sands waste materials harbored on average from 60% to 72% more
      blow fly larvae than those on the reference site. Nestlings on reclaimed sites
      suffered mean parasitic burdens about twice that of those on the reference site;
      and for comparable parasitic load, they exhibited greater pathologic effects
      (e.g., decreased body mass) than control nestlings. The heavy blow fly
      infestation on oil sands-impacted wetlands suggests that oil sands mining
      disturbs several components of the local ecosystem, including habitat
      characteristics, blow fly predators, and host resistance to parasites.

PMID- 17495302
TI  - Hookworm enteritis with bacteremia in California sea lion pups on San Miguel
      Island.
AB  - Large breeding populations of California sea lions (Zalophus californianus) are
      located on San Miguel and San Nicolas Islands in the Southern California Bight.
      In 2001, there was a substantial increase in pup mortality in late summer and
      fall. From June 2002 to January 2003, 208 freshly dead pups were examined on San
      Miguel Island, the most western of the Channel Islands off the coast of southern
      California. Tissues from 186 of these pups were examined histologically. The
      primary lesions in 133 (72%) of the pups were an enteritis associated with
      hookworms and infections in major organs. Emaciation/starvation in 43 pups (26%)
      was the second most important cause of death.

PMID- 17495303
TI  - Protostrongylid parasites and pneumonia in captive and wild thinhorn sheep (Ovis
      dalli).
AB  - We describe health significance of protostrongylid parasites (Parelaphostrongylus
      odocoilei and Protostrongylus stilesi) and other respiratory pathogens in more
      than 50 naturally infected Dall's sheep (Ovis dalli dalli) from the Mackenzie
      Mountains, Northwest Territories (1998-2002) as well as in three Stone's sheep
      (O. d. stonei) experimentally infected with P. odocoilei (2000-2002).
      Histological lesions in the brain and distribution of P. odocoilei in the muscles
      of experimentally and naturally infected sheep were consistent with a previously
      hypothesized "central nervous system to muscle" pattern of migration for P.
      odocoilei. Dimensions of granulomas associated with eggs of P. odocoilei and
      density of protostrongylid eggs and larvae in the cranial lung correlated with
      intensity of larvae in feces, and all varied with season of collection.
      Prevalence of P. stilesi based on the presence of larvae in feces underestimated
      true prevalence (based on examination of lungs) in wild Dall's sheep collected in
      summer and fall. Similarly, counts of both types of protostrongylid larvae in
      feces were unreliable indicators of parasitic infection in wild Dall's sheep with
      concomitant bacterial pneumonia associated with Arcanobacterium pyogenes,
      Pasteurella sp., and Mannheimia sp. Diffuse, interstitial pneumonia due to P.
      odocoilei led to fatal pulmonary hemorrhage and edema after exertion in one
      experimentally infected Stone's sheep and one naturally infected Dall's sheep.
      Bacterial and verminous pneumonia associated with pathogens endemic in wild
      Dall's sheep in the Mackenzie Mountains caused sporadic mortalities. There was no
      evidence of respiratory viruses or bacterial strains associated with domestic
      ruminants, from which this population of wild sheep has been historically
      isolated.

PMID- 17495304
TI  - Raptor mortality due to West Nile virus in the United States, 2002.
AB  - West Nile virus (WNV) has affected many thousands of birds since it was first
      detected in North America in 1999, but the overall impact on wild bird
      populations is unknown. In mid-August 2002, wildlife rehabilitators and local
      wildlife officials from multiple states began reporting increasing numbers of
      sick and dying raptors, mostly red-tailed hawks (Buteo jamaicensis) and great
      horned owls (Bubo virginianus). Commonly reported clinical signs were nonspecific
      and included emaciation, lethargy, weakness, inability to perch, fly or stand,
      and nonresponse to danger. Raptor carcasses from 12 states were received, and
      diagnostic evaluation of 56 raptors implicated WNV infection in 40 (71%) of these
      cases. Histologically, nonsuppurative encephalitis and myocarditis were the
      salient lesions (79% and 61%, respectively). Other causes of death included lead
      poisoning, trauma, aspergillosis, and Salmonella spp. and Clostridium spp.
      infections. The reason(s) for the reported increase in raptor mortality due to
      WNV in 2002 compared with the previous WNV seasons is unclear, and a better
      understanding of the epizootiology and pathogenesis of the virus in raptor
      populations is needed.

PMID- 17495305
TI  - Pathology and epidemiology of natural West Nile viral infection of raptors in
      Georgia.
AB  - Carcasses from 346 raptors found between August 2001 and December 2004 were
      tested for West Nile virus (WNV) using virus isolation and immunohistochemistry;
      40 were positive for WNV by one or both methods. Of these 40 birds, 35 had
      histologic lesions compatible with WNV infection, one had lesions possibly
      attributable to WNV, and four had no histologic evidence of WNV. The most common
      histologic lesions associated with WNV infection were myocardial inflammation,
      necrosis, and fibrosis; skeletal muscle degeneration, inflammation, and fibrosis;
      and lymphoplasmacytic encephalitis. Other lesions included hepatitis, lymphoid
      depletion in spleen and bursa, splenic and hepatic hemosiderosis, pancreatitis,
      and ganglioneuritis. Gross lesions included calvarial and leptomeningeal
      hemorrhage, myocardial pallor, and splenomegaly. Red-tailed hawks (Buteo
      jamaicensis) (10/56), sharp-shinned hawks (Accipiter striatus) (8/40), and
      Cooper's hawks (Accipiter cooperii) (10/103) were most commonly affected. Also
      affected were red-shouldered hawks (Buteo lineatus) (2/43), an osprey (Pandion
      haliaetus) (1/5), barred owls (Strix varia) (4/27), a great horned owl (Bubo
      virginianus) (1/18), and eastern screech owls (Megascops asio) (4/42). Although
      birds were examined throughout the year, positive cases occurred only during the
      summer and late fall (June-December). Yearly WNV mortality rates ranged from 7
      15% over the four years of the study. This study indicates trends in infection
      rates of WNV in raptorial species over a significant time period and supports the
      available information regarding pathology of WNV infection in Strigiformes and
      Falconiformes. Although many species tested were positive for WNV infection,
      severity of lesions varied among species.

PMID- 17495306
TI  - Prion protein genes in caribou from Alaska.
AB  - Prion protein genes were sequenced in free-ranging Alaska caribou (Rangifer
      tarandus grantii). Caribou prion alleles are identical or nearly so to those of
      wapiti, white-tailed deer, and mule deer. Five single-nucleotide polymorphisms
      were detected with substitutions at residues 2 (V-->M), 129 (G-->S), 138 (S-->N),
      146 (N-->N), and 169 (V-->M). The 138N codon had been previously reported only in
      prion pseudogenes of other cervids. In caribou, the 138S and 138N alleles are
      present at frequencies of approximately 0.7 and 0.3, respectively, and they are
      seen in both homozygotes and heterozygotes of three geographically separated
      herds, each a component of the continental metapopulation. Genetics seems to
      permit the spread of chronic wasting disease from middle-latitude deer to high
      latitude caribou in North America.

PMID- 17495307
TI  - Infectious disease monitoring of the endangered Hawaiian monk seal.
AB  - As part of conservation efforts between 1997 and 2001, more than 25% (332
      animals) of the endangered Hawaiian monk seal (Monachus schauinslandi) population
      was sampled in the northwestern Hawaiian Islands. Serum samples were tested for
      antibodies to viruses, bacteria, and parasites known to cause morbidity and
      mortality in other marine mammal species. Antibodies were found to phocine
      herpesvirus-1 by using an enzyme-linked immunosorbent assay, but seropositive
      results were not confirmed by virus neutralization test. Antibodies to Leptospira
      bratislava, L. hardjo, L. icterohaemorrhagiae, and L. pomona were detected in
      seals from several sites with the microagglutination test. Antibodies to Brucella
      spp. were detected using 10 conventional serologic tests, but because of
      inconsistencies in test results and laboratories used, and the lack of validation
      by culture, the Brucella serology should be interpreted with caution. Antibodies
      to B. canis were not detected by card test. Chlamydophila abortus antibodies were
      detected by complement fixation (CF) test, and prevalence increased significantly
      as a function of age; the low sensitivity and specificity associated with the CF
      make interpretation of results difficult. Antibodies to Toxoplasma gondii and
      Dirofilaria immitis were rarely found. There was no serologic evidence of
      exposure to four morbilliviruses, influenza A virus, canine adenovirus,
      caliciviruses, or other selected viruses. Continuous surveillance provides a
      means to detect the introduction or emergence of these or other infectious
      diseases, but it is dependent on the development or improvement of diagnostic
      tools. Continued and improved surveillance are both needed as part of future
      conservation efforts of Hawaiian monk seals.

PMID- 17495308
TI  - The elimination of raccoon rabies from Wolfe Island, Ontario: animal density and
      movements.
AB  - During 1996 to 1998, an average of 52% to 55% of the raccoon (Procyon lotor)
      population on Wolfe Island, Ontario was vaccinated against rabies during
      proactive trap-vaccinate-release (TVR) operations. However, during 1999, the
      percent of the population vaccinated declined to 39% and an outbreak (6 cases) of
      raccoon rabies occurred on the island from December 1999 to January 2000. The
      raccoon population on Wolfe Island declined dramatically (71% reduction) from
      1,067 raccoons (mean density = 8.4/km(2) [6.4-12.4, 95% CI]) during 1999 to 305
      raccoons (mean density = 2.4/km(2) [0.87-4.1, 95% CI]) in the spring of 2000.
      Raccoon density immediately following the outbreak was significantly lower in
      cells with rabies cases, suggesting that rabies had a negative effect on
      population size. However, raccoon density had doubled by 1 yr following the
      outbreak. Movement of raccoons on Wolfe Island was as great as 24 km. Male
      raccoons moved greater distances than females. Movements to surrounding islands
      were also noted for raccoons ear tagged on Wolfe Island which indicates the
      island could serve as a focus for greater geographic rabies spread. Point
      infection control (PIC) during 2000, TVR during 2001-02, and the aerial
      distribution of Vaccinia-Rabies Glycoprotein (V-RG) baits during 2000 and 2003-05
      were used to eliminate rabies from Wolfe Island. No cases have been detected
      since late January 2000 (to February 2007).

PMID- 17495309
TI  - Direct and indirect costs of rabies exposure: a retrospective study in southern
      California (1998-2002).
AB  - The direct and indirect costs of suspected human rabies exposure were estimated
      for San Luis Obispo and Santa Barbara counties, California, USA. Clinic,
      hospital, and county public health records (1998-2002) were examined to determine
      direct costs for postexposure prophylaxis (PEP), and 55 (41%) former patients
      were contacted to voluntarily provide estimates of their indirect costs
      associated with receiving PEP. Additional costs due to public health and animal
      control personnel responses to rabid animals were collected, including diagnostic
      testing and wages. The mean total cost of a suspected human rabies exposure was
      $3,688, the direct costs per case were $2,564, and the indirect costs were $1,124
      of that total. About one third of the total cost for suspected human rabies
      exposure was attributed to indirect costs (e.g., lost wages, transportation, and
      day-care fees), most of which were not reimbursable to the patient.

PMID- 17495310
TI  - Haptoglobin concentrations in free-range and temporarily captive juvenile steller
      sea lions.
AB  - Haptoglobin (Hp) is an acute-phase protein synthesized in the liver that
      circulates at elevated concentrations in response to tissue damage caused by
      inflammation, infection, and trauma. As part of a larger study, sera Hp
      concentrations were measured in temporarily captive (n = 21) and free-range (n =
      38) western stock juvenile Steller sea lions (Eumetopias jubatus) sampled from
      2003 to 2006. Baseline Hp concentration at time of capture was 133.3 +/- 17.4
      mg/dl. Temporarily captive animals exhibited a 3.2-fold increase in Hp
      concentrations during the first 4 wk of captivity, followed by a return to entry
      levels by week 5. Haptoglobin levels were not influenced by age, season, or
      parasite load. There was a significant positive correlation between Hp
      concentrations and white blood cell count (P < 0.001) and globulin levels (P <
      0.001) and a negative correlation to red blood cell count and hematocrit (P <
      0.001 for both). There was no correlation between Hp levels and platelet count (P
      = 0.095) or hemoglobin (P = 0.457). Routine blubber biopsies collected under gas
      anesthesia did not produce a measurable Hp response. One animal with a large
      abscess had an Hp spike of 1,006.0 mg/dl that returned to entry levels after
      treatment. In conclusion, serum Hp levels correlate to the stable clinical health
      status observed during captivity, with moderate Hp response during capture and
      initial acclimation to captivity and acute response to inflammation and
      infection.

PMID- 17495312
TI  - Intestinal Acanthocephaladiosis in Olrog's gulls (Larus atlanticus):
      Profilicollis chasmagnathi as possible cause of death.
AB  - In 2003 and 2005, mortality events were observed among hatch-year Olrog's gulls
      (Larus atlanticus) in a breeding colony in the Bahia Blanca estuary, Argentina.
      Freshly dead chicks were collected for parasitologic and parasite-associated
      pathologic studies. Profilicollis chasmagnathi was found at various intensities
      in all of the birds examined (n=28). On gross and histopathologic examinations,
      severe lesions ranging from intestinal obstruction to complete perforation were
      present in small and large intestines of the birds. Larval forms of P.
      chasmagnathi were being found in prey items of L. atlanticus in the study area,
      which suggests that diet may play a central role in the epidemiology of disease
      and mortality events in this species.

PMID- 17495311
TI  - Pruritic facial dermatitis in a population of free-living stitchbirds.
AB  - From September 2001 to February 2005, observations of an island population of the
      New Zealand stitchbird (Notiomystis cincta) revealed a progressive feather-losing
      dermatitis, which developed during the breeding season around the birds' eyes,
      base of the bill, and ventral neck. The lesions were significantly more likely to
      develop in males (96%) than females (51%), with males exhibiting a more severe
      form of the condition at the end of the breeding season. Histology from a dead
      bird revealed the presence of ovoid burrowing mites within the lesions, and
      isolation of mites from skin crusts of a live bird were identified as
      Knemidocoptes spp. Although other factors might be involved in the expression of
      the condition, Knemidocoptes appears to be a likely causative agent in the
      development of skin lesions in this population.

PMID- 17495313
TI  - Notoedric mange in two free-ranging mountain lions (Puma concolor).
AB  - Two mountain lions (Puma con-color) were found dead in the Simi Hills area of
      southern California (Ventura County). Postmortem examination and toxicological
      analyses indicated that the cause of death was anticoagulant rodenticide
      intoxication. In addition, both lions had marked alopecia and skin crusts, caused
      by Notoedres cati. The diagnosis of notoedric mange was confirmed by histology
      and direct examination of mites obtained from skin scrapings of the two animals.
      Histologically, the affected skin showed acanthotic epidermis with parakeratosis
      and parasitic tunnels in the stratum corneum. This is the first report of the
      pathological changes associated with notoedric mange in free-ranging mountain
      lions.

PMID- 17495315
TI  - Susceptibility of the endangered California tiger salamander, Ambystoma
      californiense, to ranavirus infection.
AB  - Emerging infectious diseases are implicated in the declines and extinctions of
      amphibians worldwide. Ranaviruses in the family Iridoviridae are a global concern
      and have caused amphibian die-offs in wild populations in North America, Europe,
      South America, and in commercial populations in Asia and South America. The
      movement of amphibians for bait, food, pets, and research provides a route for
      the introduction of ranaviruses into naive and potentially endangered species. In
      this report, we demonstrate that the California tiger salamander, Ambystoma
      californiense, is susceptible to Ambystoma tigrinum virus (ATV). This virus has
      not been previously reported in California tiger salamander, but observed
      mortality in experimentally infected animals suggests that California tiger
      salamander populations could be adversely affected by an ATV introduction.

PMID- 17495314
TI  - Tiletamine-zolazepam-xylazine immobilization of fishers (Martes pennanti).
AB  - The effectiveness of tiletamine plus zolazepam (Telazol) and xylazine as an
      immobilizing combination for fishers (Martes pennanti) was evaluated. Ten fishers
      were intramuscularly injected using a 5:3 mixture of Telazol (2.9+/-0.6 mg/kg
      [mean+/-SD]) and xylazine (2.1+/-0.4 mg/kg) at Pictured Rocks National Lakeshore,
      Michigan (USA) during May to October, 2001-05. Mean induction time was 4.7+/-4.4
      min; mean recovery time was 94.6+/-46.0 min. There was no relationship between
      the amount (mg/kg) of Telazol-xylazine injected and time to first effect of
      immobilants, dosage and time to induction, or between dosage and time to
      recovery. Mean heart rate remained constant through 20 min postinduction.
      Respiratory rate and body temperature declined through 10 and 20 min
      postinduction, respectively. No mortality occurred and no adverse effects were
      observed in individuals up to 19 mo later. It was concluded that a 5:3 mixture of
      Telazol-xylazine is a safe and effective immobilizing agent for fishers when
      conducting nonsurgical field procedures. Immobilizing fishers with 6-7 mg/kg of
      the combination (3.8-4.4 mg/kg Telazol and 2.3-2.6 mg/kg xylazine) should provide
      > or =30 min of handling time and allow full recovery in < 90 min.

PMID- 17495316
TI  - Rabies in bats from Alabama.
AB  - Data on rabies virus infection in bats that were submitted to the Alabama
      Department of Public Health from 1995-2005 were analyzed. Demographic factors,
      such as species and sex, and temporal aspects, such as yearly and monthly trends,
      were investigated. Thirteen species of bats were submitted, and of those,
      individuals from seven species were rabid; prevalence was highest in Lasiurus
      borealis and Pipistrellus subflavus and lowest in Eptesicus fuscus and Nycticeius
      humeralis. There was no difference in prevalence of rabies between sexes or
      years. Statistically, more rabid bats were submitted in August, September, and
      November; and fewer were submitted in March, June, and July. Results were similar
      to those from other regions of North America; these data from Alabama can help to
      present a more complete view of rabies in bats in North America.

PMID- 17495317
TI  - Rabies in vaccinated raccoons from Ontario, Canada.
AB  - From 1999 to 2006, 132 cases of raccoon rabies, caused by the raccoon variant of
      rabies virus, were confirmed in eastern Ontario, Canada. Trap-vaccinate-release
      (TVR) and point infection control (PIC) programs were implemented to control the
      disease; 43,014 raccoons (Procyon lotor) were vaccinated against rabies by
      injection (Imrab3) during that period. Two vaccinated raccoons were diagnosed
      with rabies at 6 mo and at 2 wk postvaccination. One may have been due to a
      vaccination failure. The other was likely due to the animal being in the late
      stages of incubation for rabies at the time of vaccination. This information will
      be useful to wildlife rehabilitators and agencies that hold raccoons in captivity
      in that a vaccinated raccoon is not necessarily immune to rabies.

PMID- 17495318
TI  - Mycobacterium avium subsp. paratuberculosis in scavenging mammals in Wisconsin.
AB  - The presence of Mycobacterium avium subsp. paratuberculosis (MAP) in non-ruminant
      wildlife has raised questions regarding the role of these species in Johne's
      disease transmission. In this study we tested 472 tissues from 212 animals of six
      different species of scavenging mammals. All animals were taken from within a 210
      square-mile area in Dane and Iowa counties of south central Wisconsin from
      September to May in 2003-04 and tested for the presence of MAP. We detected MAP
      specific DNA in 81 of 212 (38%) scavenging mammals, in 98 of the 472 (21%)
      tissues; viable MAP was cultured from one coyote's ileum and lymph node tissue.
      Despite the low numbers of viable MAP isolated in this study, our data adds to
      the increasing evidence demonstrating the potential for transmission and
      infection of MAP in nonruminant species and provides possible evidence of
      interspecies transmission. The apparently high exposure of nonruminant wildlife
      provides potential evidence of a spill-over of MAP to wildlife species and raises
      the question of spillback to domestic and wild ruminants. These results
      demonstrate the importance of understanding the role of wildlife species in
      developing management strategies for Johne's disease in domestic livestock.

PMID- 17495319
TI  - A natural case of chronic wasting disease in a free-ranging moose (Alces alces
      shirasi).
AB  - Chronic wasting disease (CWD) was diagnosed in a free-ranging moose (Alces alces
      shirasi) killed by a hunter in Jackson County, Colorado, USA, in September 2005.
      The diagnosis was based upon immunohistochemistry (IHC) demonstrating the
      presence of accumulations of CWD-associated prion protein (PrP(CWD)) in tissue
      sections of medulla oblongata at the level of the obex (dorsal motor nucleus of
      the vagus) and in retropharyngeal lymph node (RPLN); additional testing by IHC
      revealed deposits of PrP(CWD) in multiple sections of medulla oblongata and
      cervical spinal cord as well as palatine tonsil and submandibular lymph node
      tissues. Western blot confirmed the presence of PrP(CWD) in RPLN and tonsil
      tissue. The PrP(CWD) also was detected via enzyme-linked immunosorbent assay of
      RPLN tissue. Spongiform encephalopathy was observed in sections of the brainstem
      and cervical spinal cord, although no clinical signs were noted by the hunter who
      killed the animal. The affected moose was homozygous for methionine at codon 209
      of the prion protein coding region. In October 2006, two additional free-ranging
      moose were diagnosed with CWD. Epidemiology and implications of CWD in moose
      remain to be determined.

PMID- 17495320
TI  - Evidence of feline immunodeficiency virus, feline leukemia virus, and Toxoplasma
      gondii in feral cats on Mauna Kea, Hawaii.
AB  - We determined prevalence to feline immunodeficiency virus (FIV) antibodies,
      feline leukemia virus (FeLV) antigen, and Toxoplasma gondii antibodies in feral
      cats (Felis catus) on Mauna Kea Hawaii from April 2002 to May 2004. Six of 68
      (8.8%) and 11 of 68 (16.2%) cats were antibody positive to FIV and antigen
      positive for FeLV, respectively; 25 of 67 (37.3%) cats were seropositive to T.
      gondii. Antibodies to FeLV and T. gondii occurred in all age and sex classes, but
      FIV occurred only in adult males. Evidence of current or previous infections with
      two of these infectious agents was detected in eight of 64 cats (12.5%). Despite
      exposure to these infectious agents, feral cats remain abundant throughout the
      Hawaiian Islands.

PMID- 17495322
TI  - Inhibition of p38alpha mitogen-activated protein kinase prevents the development
      of osteolytic bone disease, reduces tumor burden, and increases survival in
      murine models of multiple myeloma.
AB  - The bone microenvironment plays a critical role in supporting the growth and
      survival of multiple myeloma as well as in the development of osteolytic bone
      disease. Signaling through p38alpha mitogen-activated protein kinase (MAPK)
      mediates synthesis of multiple myeloma cell growth factors, and its inhibition
      reduces proliferation in vitro. However, it is unclear whether targeting p38alpha
      MAPK prevents multiple myeloma growth and the development of bone disease in
      vivo. In this study, we determined whether SCIO-469, a selective p38alpha MAPK
      inhibitor, inhibits multiple myeloma growth and prevents bone disease in the
      5T2MM and 5T33MM models. SCIO-469 decreased constitutive p38alpha MAPK
      phosphorylation of both 5T2MM and 5T33MM cells in vitro. This was associated with
      decreased DNA synthesis and an induction of apoptosis when the cells were
      cultured with bone marrow stromal cells. Treatment of C57Bl/KaLwRij mice bearing
      5T33MM cells with SCIO-469 inhibited p38alpha MAPK phosphorylation and was
      associated with a significant decrease in serum paraprotein, an almost complete
      reduction in tumor cells in the bone marrow, a decrease in angiogenesis, and a
      significant increase in disease-free survival. Injection of 5T2MM murine myeloma
      cells into C57Bl/KaLwRij mice resulted in myeloma bone disease characterized by
      increased osteoclast occupation of the bone surface, reduced cancellous bone, and
      the development of osteolytic bone lesions. Treatment of 5T2MM-injected mice with
      SCIO-469 reduced this development of bone disease. Together, these data show that
      targeting p38alpha MAPK with SCIO-469 decreases myeloma burden in vivo, in
      addition to preventing the development of myeloma bone disease.

PMID- 17495324
TI  - Myeloid cell leukemia-1 inversely correlates with glycogen synthase kinase-3beta
      activity and associates with poor prognosis in human breast cancer.
AB  - Myeloid cell leukemia-1 (Mcl-1), an antiapoptotic Bcl-2 family member, is
      overexpressed in many types of human cancer and associates with cell
      immortalization, malignant transformation, and chemoresistance. Glycogen synthase
      kinase-3beta (GSK-3beta), a key component of the Wnt signaling pathway, is
      involved in multiple physiologic processes such as protein synthesis,
      tumorigenesis, and apoptosis. Here, we report that expression of Mcl-1 was
      correlated with phosphorylated GSK-3beta (p-GSK-3beta) at Ser(9) (an inactivated
      form of GSK-3beta) in multiple cancer cell lines and primary human cancer
      samples. In addition, Mcl-1 was strikingly linked with poor prognosis of human
      breast cancer, in which the high level of Mcl-1 was related to high tumor grade
      and poor survival of breast cancer patients. Furthermore, we found that
      activation of GSK-3beta could down-regulate Mcl-1 and was required for proteasome
      mediated Mcl-1 degradation. Under some physiologic conditions, such as UV
      irradiation, anticancer drug treatment, and inhibition of growth factor pathways,
      Mcl-1 was down-regulated through activation of GSK-3beta. Our results indicate
      that Mcl-1 stabilization by GSK-3beta inactivation could be involved in
      tumorigenesis and serve as a useful prognostic marker for human breast cancer.

PMID- 17495323
TI  - Enhanced hepatocyte growth factor signaling by type II transforming growth factor
      beta receptor knockout fibroblasts promotes mammary tumorigenesis.
AB  - Transforming growth factor-beta (TGF-beta) plays complex dual roles as an
      inhibitor and promoter of tumor progression. Although the influence of the
      stromal microenvironment on tumor progression is well recognized, little is known
      about the functions of TGF-beta signaling in the stroma during tumor progression.
      Using cre-lox technology, expression of the type II TGF-beta receptor was
      selectively knocked out in fibroblasts (Tgfbr2(FspKO)). In a co-xenograft model,
      we show that Tgfbr2(FspKO) fibroblasts enhance mammary carcinoma growth and
      metastasis in mice while increasing hepatocyte growth factor (HGF) expression and
      c-Met signaling downstream pathways including signal transducers and activators
      of transcription 3 (Stat3) and p42/44 mitogen-activated protein kinase (MAPK).
      Treatment of tumor-bearing mice with a pharmacologic inhibitor (EXEL-7592) of c
      Met blocks tumor progression and reduces levels of phospho-Stat3 and phospho
      p42/44 MAPK. Similarly, small interfering RNA knockdown of c-Met expression in
      mammary tumor cells reduces metastasis and c-Met signaling caused by
      Tgfbr2(FspKO) fibroblasts. The results show that TGF-beta signaling in
      fibroblasts suppresses tumor metastasis by antagonizing HGF/c-Met signaling
      within tumor epithelial cells. Furthermore, this co-xenograft model represents a
      unique context to study stromal TGF-beta and HGF signaling in mammary
      tumorigenesis.

PMID- 17495325
TI  - Computation of localized flow for steady and unsteady vector fields and its
      applications.
AB  - We present, extend, and apply a method to extract the contribution of a subregion
      of a data set to the global flow. To isolate this contribution, we decompose the
      flow in the subregion into a potential flow that is induced by the original flow
      on the boundary and a localized flow. The localized flow is obtained by
      subtracting the potential flow from the original flow. Since the potential flow
      is free of both divergence and rotation, the localized flow retains the original
      features and captures the region-specific flow that contains the local
      contribution of the considered subdomain to the global flow. In the remainder of
      the paper, we describe an implementation on unstructured grids in both two and
      three dimensions for steady and unsteady flow fields. We discuss the application
      of some widely used feature extraction methods on the localized flow and describe
      applications like reverse-flow detection using the potential flow. Finally, we
      show that our algorithm is robust and scalable by applying it to various flow
      data sets and giving performance figures.

PMID- 17495326
TI  - Tabletop computed lighting for practical digital photography.
AB  - We apply simplified image-based lighting methods to reduce the equipment, cost,
      time, and specialized skills required for high-quality photographic lighting of
      desktop-sized static objects such as museum artifacts. We place the object and a
      computer-steered moving-head spotlight inside a simple foam-core enclosure and
      use a camera to record photos as the light scans the box interior. Optimization,
      guided by interactive user sketching, selects a small set of these photos whose
      weighted sum best matches the user-defined target sketch. Unlike previous image
      based relighting efforts, our method requires only a single area light source,
      yet it can achieve high-resolution light positioning to avoid multiple sharp
      shadows. A reduced version uses only a handheld light and may be suitable for
      battery-powered field photography equipment that fits into a backpack.

PMID- 17495327
TI  - Seeing people in different light--joint shape, motion, and reflectance capture.
AB  - By means of passive optical motion capture, real people can be authentically
      animated and photo-realistically textured. To import real-world characters into
      virtual environments, however, surface reflectance properties must also be known.
      We describe a video-based modeling approach that captures human shape and motion
      as well as reflectance characteristics from a handful of synchronized video
      recordings. The presented method is able to recover spatially varying surface
      reflectance properties of clothes from multiview video footage. The resulting
      model description enables us to realistically reproduce the appearance of
      animated virtual actors under different lighting conditions, as well as to
      interchange surface attributes among different people, e.g., for virtual
      dressing. Our contribution can be used to create 3D renditions of real-world
      people under arbitrary novel lighting conditions on standard graphics hardware.

PMID- 17495328
TI  - Topology repair of solid models using skeletons.
AB  - We present a method for repairing topological errors on solid models in the form
      of small surface handles, which often arise from surface reconstruction
      algorithms. We utilize a skeleton representation that offers a new mechanism for
      identifying and measuring handles. Our method presents two unique advantages over
      previous approaches. First, handle removal is guaranteed not to introduce invalid
      geometry or additional handles. Second, by using an adaptive grid structure, our
      method is capable of processing huge models efficiently at high resolutions.

PMID- 17495329
TI  - Stereoscopic video synthesis from a monocular video.
AB  - This paper presents an automatic and robust approach to synthesize stereoscopic
      videos from ordinary monocular videos acquired by commodity video cameras.
      Instead of recovering the depth map, the proposed method synthesizes the
      binocular parallax in stereoscopic video directly from the motion parallax in
      monocular video. The synthesis is formulated as an optimization problem via
      introducing a cost function of the stereoscopic effects, the similarity, and the
      smoothness constraints. The optimization selects the most suitable frames in the
      input video for generating the stereoscopic video frames. With the optimized
      selection, convincing and smooth stereoscopic video can be synthesized even by
      simple constant-depth warping. No user interaction is required. We demonstrate
      the visually plausible results obtained given the input clips acquired by
      ordinary handheld video camera.

PMID- 17495330
TI  - Space-time light field rendering.
AB  - In this paper, we propose a novel framework called space-time light field
      rendering, which allows continuous exploration of a dynamic scene in both space
      and time. Compared to existing light field capture/rendering systems, it offers
      the capability of using unsynchronized video inputs and the added freedom of
      controlling the visualization in the temporal domain, such as smooth slow motion
      and temporal integration. In order to synthesize novel views from any viewpoint
      at any time instant, we develop a two-stage rendering algorithm. We first
      interpolate in the temporal domain to generate globally synchronized images using
      a robust spatial-temporal image registration algorithm followed by edge
      preserving image morphing. We then interpolate these software-synchronized images
      in the spatial domain to synthesize the final view. In addition, we introduce a
      very accurate and robust algorithm to estimate subframe temporal offsets among
      input video sequences. Experimental results from unsynchronized videos with or
      without time stamps show that our approach is capable of maintaining
      photorealistic quality from a variety of real scenes.

PMID- 17495331
TI  - Derivative particles for simulating detailed movements of fluids.
AB  - We present a new fluid simulation technique that significantly reduces the
      nonphysical dissipation of velocity. The proposed method is based on an apt use
      of particles and derivative information. We note that a major source of numerical
      dissipation in the conventional Navier-Stokes equations solver lies in the
      advection step. Hence, starting with the conventional grid-based simulator, when
      the details of fluid movements need to be simulated, we replace the advection
      part with a particle simulator. When swapping between the grid-based and particle
      based simulators, the physical quantities such as the level set and velocity must
      be converted. For this purpose, we develop a novel dissipation-suppressing
      conversion procedure that utilizes the derivative information stored in the
      particles, as well as in the grid points. For the fluid regions where such
      details are not needed, the advection is simulated using an octree-based
      constrained interpolation profile (CIP) solver, which we develop in this work.
      Through several experiments, we show that the proposed technique can reproduce
      the detailed movements of high-Reynolds-number fluids such as droplets/bubbles,
      thin water sheets, and whirlpools. The increased accuracy in the advection, which
      forms the basis of the proposed technique, can also be used to produce better
      results in larger scale fluid simulations.

PMID- 17495332
TI  - Isocube: exploiting the cubemap hardware.
AB  - This paper proposes a novel six-face spherical map, isocube, that fully utilizes
      the cubemap hardware built in most GPUs. Unlike the cubemap, the proposed isocube
      uniformly samples the unit sphere (uniformly distributed), and all samples span
      the same solid angle (equally important). Its mapping computation contains only a
      small overhead. By feeding the cubemap hardware with the six-face isocube map,
      the isocube can exploit all built-in texturing operators tailored for the cubemap
      and achieve a very high frame rate. In addition, we develop an anisotropic
      filtering that compensates aliasing artifacts due to texture magnification. This
      filtering technique extends the existing hardware anisotropic filtering and can
      be applied not only to the proposed isocube, but also to other texture mapping
      applications.

PMID- 17495333
TI  - Data-driven grasp synthesis using shape matching and task-based pruning.
AB  - Human grasps, especially whole-hand grasps, are difficult to animate because of
      the high number of degrees of freedom of the hand and the need for the hand to
      conform naturally to the object surface. Captured human motion data provides us
      with a rich source of examples of natural grasps. However, for each new object,
      we are faced with the problem of selecting the best grasp from the database and
      adapting it to that object. This paper presents a data-driven approach to grasp
      synthesis. We begin with a database of captured human grasps. To identify
      candidate grasps for a new object, we introduce a novel shape matching algorithm
      that matches hand shape to object shape by identifying collections of features
      having similar relative placements and surface normals. This step returns many
      grasp candidates, which are clustered and pruned by choosing the grasp best
      suited for the intended task. For pruning undesirable grasps, we develop an
      anatomically-based grasp quality measure specific to the human hand. Examples of
      grasp synthesis are shown for a variety of objects not present in the original
      database. This algorithm should be useful both as an animator tool for posing the
      hand and for automatic grasp synthesis in virtual environments.

PMID- 17495334
TI  - Blood flow in its context: combining 3D B-mode and color Doppler ultrasonic data.
AB  - Visualization of volumetric multicomponent data sets is a high-dimensional
      problem, especially for color data. Medical 3D ultrasound (US) technology has
      rapidly advanced during the last few decades and scanners can now generate joint
      3D scans of tissues (B-mode) and blood flow (power or color Doppler) in real
      time. Renderings of such data sets have to comprehensively convey both the
      relevant structures of the tissues that form the context for blood flow, as well
      as the distribution of blood flow itself. The narrow field of view in US data,
      which is often used to make real-time imaging possible, complicates volume
      exploration since only parts of organs are usually visible; that is, clearly
      defined anatomical landmarks are scarce. In addition, the noisy nature and low
      signal-to-contrast ratio of US data make effective visualization a challenge,
      whereby there are currently no convincing solutions for combined US B-mode and
      color Doppler data rendering. Therefore, displaying 2D slices out of the 3D data
      is still often the preferred visualization method. We present new combinations of
      photorealistic and nonphotorealistic rendering strategies for combined
      visualization of B-mode and color Doppler data, which are straightforward to
      implement, flexible, and suited for a wide range of US applications.

PMID- 17495335
TI  - A coherent grid traversal approach to visualizing particle-based simulation data.
AB  - We present an approach to visualizing particle-based simulation data using
      interactive ray tracing and describe an algorithmic enhancement that exploits the
      properties of these data sets to provide highly interactive performance and
      reduced storage requirements. This algorithm for fast packet-based ray tracing of
      multilevel grids enables the interactive visualization of large time-varying data
      sets with millions of particles and incorporates advanced features like soft
      shadows. We compare the performance of our approach with two recent particle
      visualization systems: one based on an optimized single ray grid traversal
      algorithm and the other on programmable graphics hardware. This comparison
      demonstrates that the new algorithm offers an attractive alternative for
      interactive particle visualization.

PMID- 17495336
TI  - Vector field editing and periodic orbit extraction using Morse decomposition.
AB  - Design and control of vector fields is critical for many visualization and
      graphics tasks such as vector field visualization, fluid simulation, and texture
      synthesis. The fundamental qualitative structures associated with vector fields
      are fixed points, periodic orbits, and separatrices. In this paper, we provide a
      new technique that allows for the systematic creation and cancellation of fixed
      points and periodic orbits. This technique enables vector field design and
      editing on the plane and surfaces with desired qualitative properties. The
      technique is based on Conley theory, which provides a unified framework that
      supports the cancellation of fixed points and periodic orbits. We also introduce
      a novel periodic orbit extraction and visualization algorithm that detects, for
      the first time, periodic orbits on surfaces. Furthermore, we describe the
      application of our periodic orbit detection and vector field simplification
      algorithms to engine simulation data demonstrating the utility of the approach.
      We apply our design system to vector field visualization by creating data sets
      containing periodic orbits. This helps us understand the effectiveness of
      existing visualization techniques. Finally, we propose a new streamline-based
      technique that allows vector field topology to be easily identified.

PMID- 17495337
TI  - Style grammars for interactive visualization of architecture.
AB  - Interactive visualization of architecture provides a way to quickly visualize
      existing or novel buildings and structures. Such applications require both fast
      rendering and an effortless input regimen for creating and changing architecture
      using high-level editing operations that automatically fill in the necessary
      details. Procedural modeling and synthesis is a powerful paradigm that yields
      high data amplification and can be coupled with fast-rendering techniques to
      quickly generate plausible details of a scene without much or any user
      interaction. Previously, forward generating procedural methods have been proposed
      where a procedure is explicitly created to generate particular content. In this
      paper, we present our work in inverse procedural modeling of buildings and
      describe how to use an extracted repertoire of building grammars to facilitate
      the visualization and quick modification of architectural structures and
      buildings. We demonstrate an interactive application where the user draws simple
      building blocks and, using our system, can automatically complete the building
      "in the style of" other buildings using view-dependent texture mapping or
      nonphotorealistic rendering techniques. Our system supports an arbitrary number
      of building grammars created from user subdivided building models and captured
      photographs. Using only edit, copy, and paste metaphors, the entire building
      styles can be altered and transferred from one building to another in a few
      operations, enhancing the ability to modify an existing architectural structure
      or to visualize a novel building in the style of the others.

PMID- 17495338
TI  - NPU-based image compositing in a distributed visualization system.
AB  - This paper describes the first use of a Network Processing Unit (NPU) to perform
      hardware-based image composition in a distributed rendering system. The image
      composition step is a notorious bottleneck in a clustered rendering system.
      Furthermore, image compositing algorithms do not necessarily scale as data size
      and number of nodes increase. Previous researchers have addressed the composition
      problem via software and/or custom-built hardware. We used the heterogeneous
      multicore computation architecture of the Intel IXP28XX NPU, a fully programmable
      commercial off-the-shelf (COTS) technology, to perform the image composition
      step. With this design, we have attained a nearly four-times performance increase
      over traditional software-based compositing methods, achieving sustained
      compositing rates of 22-28 fps on a 1,024 x 1,024 image. This system is fully
      scalable with a negligible penalty in frame rate, is entirely COTS, and is
      flexible with regard to operating system, rendering software, graphics cards, and
      node architecture. The NPU-based compositor has the additional advantage of being
      a modular compositing component that is eminently suitable for integration into
      existing distributed software visualization packages.

PMID- 17495339
TI  - Runtime visualization of the human arterial tree.
AB  - Large-scale simulation codes typically execute for extended periods of time and
      often on distributed computational resources. Because these simulations can run
      for hours, or even days, scientists like to get feedback about the state of the
      computation and the validity of its results as it runs. It is also important that
      these capabilities be made available with little impact on the performance and
      stability of the simulation. Visualizing and exploring data in the early stages
      of the simulation can help scientists identify problems early, potentially
      avoiding a situation where a simulation runs for several days, only to discover
      that an error with an input parameter caused both time and resources to be
      wasted. We describe an application that aids in the monitoring and analysis of a
      simulation of the human arterial tree. The application provides researchers with
      high-level feedback about the state of the ongoing simulation and enables them to
      investigate particular areas of interest in greater detail. The application also
      offers monitoring information about the amount of data produced and data transfer
      performance among the various components of the application.

PMID- 17495340
TI  - Value-cell bar charts for visualizing large transaction data sets.
AB  - One of the common problems businesses need to solve is how to use large volumes
      of sales histories, Web transactions, and other data to understand the behavior
      of their customers and increase their revenues. Bar charts are widely used for
      daily analysis, but only show highly aggregated data. Users often need to
      visualize detailed multidimensional information reflecting the health of their
      businesses. In this paper, we propose an innovative visualization solution based
      on the use of value cells within bar charts to represent business metrics. The
      value of a transaction can be discretized into one or multiple cells: high-value
      transactions are mapped to multiple value cells, whereas many small-value
      transactions are combined into one cell. With value-cell bar charts, users can 1)
      visualize transaction value distributions and correlations, 2) identify high
      value transactions and outliers at a glance, and 3) instantly display values at
      the transaction record level. Value-Cell Bar Charts have been applied with
      success to different sales and IT service usage applications, demonstrating the
      benefits of the technique over traditional charting techniques. A comparison with
      two variants of the well-known Treemap technique and our earlier work on Pixel
      Bar Charts is also included.

PMID- 17495341
TI  - Terrain synthesis from digital elevation models.
AB  - In this paper, we present an example-based system for terrain synthesis. In our
      approach, patches from a sample terrain (represented by a height field) are used
      to generate a new terrain. The synthesis is guided by a user-sketched feature map
      that specifies where terrain features occur in the resulting synthetic terrain.
      Our system emphasizes large-scale curvilinear features (ridges and valleys)
      because such features are the dominant visual elements in most terrains. Both the
      example height field and user's sketch map are analyzed using a technique from
      the field of geomorphology. The system finds patches from the example data that
      match the features found in the user's sketch. Patches are joined together using
      graph cuts and Poisson editing. The order in which patches are placed in the
      synthesized terrain is determined by breadth-first traversal of a feature tree
      and this generates improved results over standard raster-scan placement orders.
      Our technique supports user-controlled terrain synthesis in a wide variety of
      styles, based upon the visual richness of real-world terrain data.

PMID- 17495342
TI  - Multicolour FISH in an analysis of chromosome aberrations induced by N-nitroso-N
      methylurea and maleic hydrazide in barley cells.
AB  - The present study is a rare example of a detailed characterization of chromosomal
      aberrations by identification of individual chromosomes (or chromosome arms)
      involved in their formation in plant cells by using fluorescent in situ
      hybridization (FISH). In addition, the first application of more than 2 DNA
      probes in FISH experiments in order to analyse chromosomal aberrations in plant
      cells is presented. Simultaneous FISH with 5S and 25S rDNA and, after reprobing
      of preparations, telomeric and centromeric DNA sequences as probes, were used to
      compare the cytogenetic effects of 2 chemical mutagens: N-nitroso-N-methylurea
      (MNU) and maleic hydrazide (MH) on root tip meristem cells of Hordeum vulgare
      (2n=14). The micronucleus (MN) test combined with FISH allowed the quantitative
      analysis of the involvement of specific chromosome fragments in micronuclei
      formation and thus enabled the possible origin of mutagen-induced micronuclei to
      be explained. Terminal deletions were most frequently caused by MH and MNU. The
      analysis of the frequency of micronuclei with signals of the investigated DNA
      probes showed differences between the frequency of MH- and MNU-induced
      micronuclei with specific signals. The micronuclei with 2 signals, telomeric DNA
      and rDNA (5S and/or 25S rDNA), were the most frequently observed in the case of
      both mutagens, but with a higher frequency after treatment with MH (46%) than MNU
      (37%). Also, 10% of MH-induced micronuclei were characterized by the presence of
      only telomere DNA sequences, whereas there were almost 3-fold more in the case of
      MNU-induced micronuclei (28%). Additionally, by using FISH with the same probes,
      an attempt was made to identify the origin of chromosome fragments in mitotic
      anaphase.

PMID- 17495343
TI  - IRAP and REMAP assessments of genetic similarity in rice.
AB  - Rice is a model genome for cereal research, providing important information about
      genome structure and evolution. Retrotransposons are common components of grass
      genomes, showing activity at transcription, translation and integration levels.
      Their abundance and ability to transpose make them good potential markers. In
      this study, we used 2 multilocus PCR-based techniques that detect retrotransposon
      integration events in the genome: IRAP (inter-retrotransposon amplified
      polymorphism) and REMAP (retrotransposon-microsatellite amplified polymorphism).
      Markers derived from Tos17, a copia-like endogenous retrotransposon of rice, were
      used to identify genetic similarity among 51 rice cultivars (Oryza sativa L.).
      Genetic similarity analysis was performed by means of the Dice coefficient, and
      dendrograms were developed by using the average linkage distance method. A
      cophenetic correlation coefficient was also calculated. The clustering techniques
      revealed a good adjustment between matrices, with correlation coefficients of
      0.74 and 0.80, or lower (0.21) but still significant, between IRAP and REMAP
      based techniques. Consistent clusters were found for Japanese genotypes, while a
      subgroup clustered the irrigated Brazilian genotypes.

PMID- 17495344
TI  - Molecular identification of new varieties of Nierembergia linariaefolia (Graham),
      a native Argentinean ornamental plant.
AB  - Six Nierembergia linariaefolia clones were selected for ornamental traits during
      a native germplasm development program. For fingerprinting diagnosis, 13 anchored
      inter-simple sequence repeat (ISSR) primers and 6 amplified fragment length
      polymorphism (AFLP) primer-enzyme combinations were used. Both markers revealed
      high levels of polymorphism, enabling genetic discrimination of the accessions
      analyzed by using 443 informative ISSRs and 541 AFLP markers. Both molecular
      techniques are suitable for monitoring genetic diversity in Nierembergia
      linariaefolia and, under our experimental conditions, they showed correlation
      coefficients of 0.629 for similarity matrices and of 0.649 in the cophenetic
      matrices. These results suggest that ISSRs are a good choice for DNA analysis in
      N. linariaefolia when simple manipulation and a low budget are required.

PMID- 17495345
TI  - Genetic base of tea (Camellia sinensis L.) cultivars in Sri Lanka as revealed by
      pedigree analysis.
AB  - An understanding of genetic diversity and relationships among breeding materials
      is a prerequisite for crop improvement. Coefficient of parentage (COP) can be
      used to measure the genetic diversity among genotypes on the basis of pedigree
      information. In the present study, COP was estimated for 56 cultivars, including
      commercial tea cultivars developed by the Tea Research Institute of Sri Lanka and
      their parental lines. Mean COP of the 56 accessions studied was 0.097 and the
      value was raised up to 0.272 when non-related pair-wise comparisons were
      excluded. A single cultivar (Assam/Cambod introduction) was the nucleus of the
      commercial cultivars. Group mean COP of the cultivars derived from Assam/Cambod
      parentage was 0.17. Thirty-three percent of the pair-wise comparisons had 0.00
      COP, highlighting that many cultivars were unrelated. Within the pedigree, 2
      major COP clusters were identified: Assam/Cambod open-pollinated half-sib
      progenies, and full-sib progenies derived from crosses between Assam/Cambod and
      other parental lines. The elite groups within the pedigree, where Assam/Cambod
      parentage was concentrated, were also identified. Information generated in this
      study should be useful for effective utilization of available diversity in future
      breeding programmes as well as for proper conservation of genetic diversity in
      the adapted germplasm. This is the first report on estimates of genetic diversity
      based on COP in a woody perennial crop, such as tea.

PMID- 17495346
TI  - Identification of molecular markers for selection of supermale (YY) asparagus
      plants.
AB  - The research was aimed to elaborate a method for selection of male plants (XY,
      YY) and female ones (XX) as well as for identification of supermale genotypes
      (YY) among male phenotypes. The population obtained by self-pollination of
      andromonoecious plants was analysed. In order to identify the bands
      differentiating the male from the female genotypes, Bulk Segregant Analysis (BSA)
      was carried out. Primers identified by BSA analysis were used for RAPD
      amplification on the template of the male and female individuals. Among the
      products obtained by the use of primer OPB-20, some bands were linked with sex. A
      band of about 700 bp was found in all female plants, and in 4 phenotypically male
      specimens. In the male plants, the band showed a much lower intensity, compared
      with the female specimens. It seems that this fragment can be linked to the X
      chromosome in the investigated specimens. In the female specimens with XX
      karyotype, template duplication occurs and hence the band intensity is twice as
      high as in the XY karyotype. Three male plants did not include the OPB-20-700
      fragment so they could potentially have the supermale (YY) karyotype. If the
      obtained marker proved its usefulness for identification of supermale plants, it
      could become a valuable tool facilitating breeding work.

PMID- 17495347
TI  - Differentially expressed genes in adipose tissues of high body weight-selected
      (obese) and unselected (lean) mouse lines.
AB  - Recently, quantitative trait loci (QTLs) for body weight and obesity have been
      mapped in an intercross population between the high body weight-selected mouse
      line DU6i and the inbred line DBA/2. Most QTLs were highly significant, but had
      small effects only. Under the hypothesis that small-effect QTLs might result from
      changes in gene activity, our strategy to identify candidate genes for the
      observed effects was directed towards the identification of differentially
      expressed genes. Therefore, here we compare the transcription profile of about 11
      000 genes in epididymal fat tissues of males of two high body weight-selected
      (DU6 and DU6i) and two unselected mouse lines (DUKs and DBA/2). For the
      hybridisation of GeneChips, we used pooled samples of 20 individual mice. By pair
      wise comparisons between selected and unselected mouse lines, a set of 77 genes
      was identified representing genes whose level of expression differed between
      obese and lean mouse strains. According to the functional classification of
      genes, 69 differentially expressed genes were involved in regulatory and
      metabolic pathways, cell division, cell stability, or immune response, and thus
      might have an effect on body weight and fat accumulation. 14 out of these genes,
      occur in QTL regions for body weight or abdominal fat weight. Further analyses
      are necessary to discriminate between genes directly causing QTL effects and
      indirectly regulated differentially expressed genes.

PMID- 17495348
TI  - Genetic evaluation of performance traits in Brazilian Quarter Horse.
AB  - The aim of this study was to estimate genetic parameters for racing performance
      traits in Quarter Horses in Brazil. The data (provided by the Sorocaba Jockey
      Club) came from 3 Brazilian hippodromes in 1994-2003, with 11 875 observations of
      race time and 7775 of the speed index (SI), distributed in 2403 and 2169 races,
      respectively. The variance components were estimated by the MTGSAM program, under
      animal models including the random additive genetic effect, random permanent
      environmental effect, and the fixed effects of sex, age and race. Heritabilities
      for race time and the SI, for the 3 distances studied (301, 365 and 402 m),
      varied from 0.26 to 0.41 and from 0.14 to 0.19, respectively, whereas
      repeatabilities varied from 0.36 to 0.68 (time) and from 0.27 to 0.42 (SI) and
      the genetic correlations from 0.90 to 0.97 (time) and from 0.67 to 0.73 (SI).

PMID- 17495349
TI  - Low incidence of bovine leukocyte adhesion deficiency (BLAD) carriers in Indian
      cattle and buffalo breeds.
AB  - BLAD is an autosomal recessive genetic disease that affects Holstein-Friesian
      (HF) cattle worldwide. It is a disease characterized by a reduced expression of
      the adhesion molecules on neutrophils. The disease is caused by a mutation that
      replaces adenine at 383 with guanine, which causes an amino acid change from
      aspartic acid to glycine. Blood samples and a few semen samples were collected
      from 1250 phenotypically normal individuals, including HF (N=377), HF crossbred
      (N=334), Jersey (105), other breeds of cattle (N=160) and water buffalo Bubalus
      bubalis (N=274) belonging to various artificial insemination stations, bull
      mother farms (BMFs) and embryo transfer (ET) centres across the country. PCR-RFLP
      was performed to detect a point mutation in CD18, surface molecules of
      neutrophils. The results indicate that out of 1250 cattle and buffaloes tested
      for BLAD, 13 HF purebreds out of 377 and 10 HF crossbreds out of 334 appear to be
      BLAD carriers. In the HF and HF crossbred population, the percentage of BLAD
      carriers was estimated as 3.23%. The condition is alarming as the mutant gene has
      already entered the HF crossbred cattle population and therefore, the population
      of HF and its crossbreds needs regular screening to avoid the risk of spreading
      BLAD in the breeding cattle population of India.

PMID- 17495350
TI  - Chromosome abnormalities without phenotypic consequences.
AB  - Some changes in chromosome morphology, detected during cytogenetic analysis, are
      not associated with clinical defects. Therefore a proper discrimination of
      harmless variants from true abnormalities, especially during prenatal diagnosis,
      is crucial to allow precise counseling. In this review we described chromosome
      variants and examples of chromosome anomalies that are considered to be unrelated
      to phenotypic consequences. The correlation between the presence of marker
      chromosomes and a risk of clinical signs is also discussed. Structural
      rearrangements of heterochromatic material, satellite polymorphism, or fragile
      sites, are well-known examples of common chromosome variation. However, the
      absence of clinical effects has also been reported in some cases of chromosome
      abnormalities concerning euchromatin. Such euchromatic anomalies were divided
      into 2 categories: unbalanced chromosome abnormalities (UBCAs), such as deletions
      or duplications, and euchromatic variants (EVs). Recently so-called molecular
      karyotyping, especially whole-genome screening by the use of high-resolution
      array-CGH technique, contributed to revealing a high number of previously unknown
      small genomic variations, which seem to be asymptomatic, as they are present in
      phenotypically normal individuals.

PMID- 17495351
TI  - Molecular cytogenetic characterization of eight small supernumerary marker
      chromosomes originating from chromosomes 2, 4, 8, 18, and 21 in three patients.
AB  - Small supernumerary marker chromosomes (sSMCs) are a morphologically
      heterogeneous group of additional structurally abnormal chromosomes that cannot
      be identified unambiguously by conventional banding techniques alone. Molecular
      cytogenetic methods enable detailed characterization of sSMCs; however, in many
      cases interpretation of their clinical significance is problematic. The aim of
      our study was to characterize precisely sSMCs identified in three patients with
      dysmorphic features, psychomotor retardation and multiple congenital anomalies.
      We also attempted to correlate the patients' genotypes with phenotypes by
      inclusion of data from the literature. The sSMCs were initially detected by G
      banding analysis in peripheral blood lymphocytes in these patients and were
      subsequently characterized using multicolor fluorescence in situ hybridization (M
      FISH), (sub)centromere-specific multicolor FISH (cenM-FISH, subcenM-FISH), and
      multicolor banding (MCB) techniques. Additionally, the sSMCs in two patients were
      also studied by hybridization to whole-genome bacterial artificial chromosome
      (BAC) arrays (array-CGH) to map the breakpoints on a single BAC clone level. In
      all three patients, the chromosome origin, structure, and euchromatin content of
      the sSMCs were determined. In patient RS, only a neocentric r(2)(q35q36) was
      identified. It is a second neocentric sSMC(2) in the literature and the first
      marker chromosome derived from the terminal part of 2q. In the other two
      patients, two sSMCs were found, as M-FISH detected additional sSMCs that could
      not be characterized in G-banding analysis. In patient MK, each of four cell
      lines contained der(4)(:p11.1-->q12:) accompanied by a sSMC(18): r(18)(:p11.2-
      >q11.1::p11.2-->q11.1:), inv dup(18)(:p11.1-->q11.1::q11.1-->p11.1:), or der(18)
      (:p11.2-->q11.1::q11.1-->p11.1:). In patient NP, with clinical features of
      trisomy 8p, three sSMCs were characterized: r(8)(:p12-->q11.1::q11.1-->p21:)
      der(8) (:p11.22-->q11.1::q11.1-->p21::p21-->p11.22:) and der(21)(:p11.1-
      >q21.3:). The BAC array results confirmed the molecular cytogenetic results and
      refined the breakpoints to the single BAC clone resolution. However, the complex
      mosaic structure of the marker chromosomes derived from chromosomes 8 and 18
      could only be identified by molecular cytogenetic methods. This study confirms
      the usefulness of multicolor FISH combined with whole-genome arrays for
      comprehensive analyses of marker chromosomes.

PMID- 17495352
TI  - P53 mutations in urinary bladder cancer patients from Central Poland.
AB  - The present study aimed at detection of P53 gene mutations in cells of urinary
      bladder neoplasms, as the mutations may be regarded as an independent prognostic
      factor for progression and recurrence of tumours. In the study, 82 patients with
      clinically diagnosed urinary bladder tumour were included. The control was
      composed of DNA samples from urine and blood of 202 healthy patients. Exons 5-8
      of the P53 gene were screened for mutations by using multitemperature single
      strand conformational polymorphism (MSSCP) analysis. Samples with abnormal MSSCP
      patterns were subjected to direct sequencing. The frequency of mutations in exons
      5-8 of the P53 gene in patients with bladder cancer was lower (3.3% in grade G1,
      24% in G2, and 39% in G3) than the data reported in the literature. We found a
      higher percentage of polymorphism at codon 213 of the P53 gene in bladder cancer
      patients (6%), compared with the values in the reference group (2.5%). These
      results were matched with those of the loss of heterozygosity (LOH) analysis. In
      conclusion, mutations were found mainly in more advanced histopathological and
      clinical stages of the disease and at the CIS stage (carcinoma in situ). It
      cannot be excluded that the observed polymorphism at codon 213 may be a
      predisposing factor for urinary bladder carcinoma development.

PMID- 17495353
TI  - Mutation of the MYH7 gene in a child with hypertrophic cardiomyopathy and Wolff
      Parkinson-White syndrome.
AB  - Familial hypertrophic cardiomyopathy (HCM) displays autosomal dominant
      inheritance with incomplete penetration of defective genes. Data concerning the
      familial occurrence of ventricular preexcitation, i.e. Wolff-Parkinson-White
      (WPW) syndrome, also indicate autosomal dominant inheritance. In the literature,
      only a gene mutation on chromosome 7q3 has been described in familial HCM
      coexisting with WPW syndrome to date. The present paper describes the case of a 7
      year-old boy with HCM and coexisting WPW syndrome. On his chromosome 14,
      molecular diagnostics revealed a C 9123 mutation (arginine changed into cysteine
      in position 453) in exon 14 in a copy of the gene for beta-myosin heavy chain
      (MYH7). It is the first known case of mutation of the MYH7 gene in a child with
      both HCM and WPW. Since no linkage between MYH7 mutation and HCM with WPW
      syndrome has been reported to date, we cannot conclude whether the observed
      mutation is a common cause for both diseases, or this patient presents an
      incidental co-occurrence of HCM (caused by MYH7 mutation) and WPW syndrome.

PMID- 17495355
TI  - The retinoid induced pancreatic cancer redifferentiation-apoptosis sequence and
      the mitochondria: a suggested obligatory sequence of events.
AB  - Retinoic acid induces redifferentiation and apoptosis in pancreatic
      adenocarcinoma cell lines. Redifferentiation includes early reversion into
      aerobic metabolism as reflected by an increase of mitochondrial activity and mass
      with normal membrane potential and terminal ductal cell differentiation. Cells in
      such a state either attempt to correct their DNA abnormalities or commit suicide
      by apoptosis. In some cell systems, such as pancreatic ductal cells, the stem
      cells show potential to transdifferentiate into functional normal endocrine cell
      type. However, since it is impossible to correct a highly corrupted genome, cells
      eventually succumb to apoptosis. Mitochondrial changes appear to be the enforcing
      factor for this process. The Transformation--Normalizing-redifferentiation-
      Apoptosis sequence has been shown by several studies, utilizing various cell
      types, apoptotic inducers, biomarkers and time frames. Although some studies have
      shown concomitant apoptosis and redifferentiation, others have reported apoptosis
      without prior redifferentiation. However, utilizing the appropriate time frame
      and the markers of earlier mitochondrial changes, one would detect a scenario
      similar to the retinoid model. This situation can be achieved by delaying
      apoptosis or reducing the inducer concentration in such systems. The final
      physiological fate of a normal terminally differentiated cells is apoptosis.
      Similarly, it is suggested that a degree of normalizing redifferentiation of
      transformed cells might be expected prior to apoptosis. The former seemed
      obligatory at least in the retinoid-pancreatic model.

PMID- 17495356
TI  - Is there an optimal neoadjuvant therapy for locally advanced pancreatic cancer?
AB  - Treatment of locally advanced pancreatic cancer is challenging. Despite
      continuing research, effective treatments continue to be elusive with median
      survival of only 8-12 months. Treatment options for locally advanced pancreatic
      cancer include radiation therapy, concurrent chemoradiation or chemotherapy. It
      is felt that radiation therapy is a suboptimal treatment as most of patients will
      die of systemic disease. In the past, radiation with 5-FU was the standard
      treatment for locally advanced pancreatic cancer. But now radiation has been used
      with combination other chemo agents such as paclitaxel or gemcitabine in order to
      increase the efficacy. Chemotherapy such as gemcitabine alone or gemcitabine
      doublet also has been studied in patients with locally advanced pancreatic cancer
      as well with overall survival being approximately the same magnitude as
      chemoradiation. The exact role of chemoradiation or chemotherapy in treatment of
      locally advanced pancreatic cancer is yet to be defined. Hence, this review
      summarizes and compares of role of radiation, chemoradiation and chemotherapy in
      treating this disease.

PMID- 17495357
TI  - Gene polymorphisms of the macrophage migration inhibitory factor and acute
      pancreatitis.
AB  - CONTEXT: Macrophage migration inhibitory factor (MIF) is a proinflammatory
      cytokine that is released by macrophages and lymphocytes and plays an important
      pathogenetic role in acute pancreatitis. It is present in large amounts in the
      serum and ascitic fluid in rats with experimental pancreatitis and its levels are
      elevated in humans with pancreatitis. Polymorphisms associated with inflammatory
      joint diseases exist in the promoter region of the macrophage migration
      inhibitory factor gene that alter its expression. OBJECTIVE: We investigated the
      association of macrophage migration inhibitory factor polymorphisms with acute
      pancreatitis in a population in the UK. PARTICIPANTS: A cohort of 164 patients
      with acute pancreatitis and 197 healthy controls. MAIN OUTCOME MEASURES: The -173
      G to C single nucleotide polymorphism and the -794 (CATT) n repeat microsatellite
      were investigated. Restriction fragment length polymorphism (RFLP) was used to
      assay the -173 polymorphism and PCR followed by polyacrylamide gel
      electrophoresis (PAGE) was used for the microsatellite. RESULTS: The
      microsatellite did not show any significant differences in distribution between
      patients and controls. The -173 GG genotype showed a trend towards reduced
      frequency seen in patients (P=0.056) and the C allele was significantly over
      expressed in patients (P=0.025). No differences were observed in subgroups based
      on severity or aetiology of pancreatitis. CONCLUSIONS: The -173 C allele is over
      expressed in acute pancreatitis, however studies are needed to explore this
      further. Our distribution of the microsatellite alleles was quite different to a
      previously reported Caucasian population and needs further study from viewpoint
      of population genetics.

PMID- 17495358
TI  - Nuclear expression of E-cadherin in solid pseudopapillary tumors of the pancreas.
AB  - CONTEXT: Solid pseudopapillary tumors of the pancreas are rare and have recently
      been shown to harbor mutations of the beta-catenin gene with resultant nuclear
      localization of beta-catenin protein to the nucleus. Moreover, there is a close
      relationship between beta-catenin and E-cadherin. OBJECTIVE: To explore the
      protein expression of E-cadherin in a series of solid pseudopapillary tumors of
      the pancreas. PARTICIPANTS: Eighteen cases of solid pseudopapillary tumors of the
      pancreas. DESIGN: The cases were studied using a tissue microarray that was
      constructed as follows: for each case, 4 to 14 cores measuring 1.0 mm each were
      drilled from the blocks. Tissue cores from normal pancreas were used as controls
      and for orientation purposes. MAIN OUTCOME MEASURES: The slides were stained with
      the following commercially available antibodies: CD10, CD56, vimentin, alpha-1
      antitrypsin, alpha-1-antichymotrypsin, neuron-specific enolase, chromogranin,
      synaptophysin, beta-catenin and E-cadherin. RESULTS: All the tumors were CD10,
      vimentin, alpha-1-antitrypsin and alpha-1-antichymotrypsin diffusely positive
      (50% or more of the tumor cells staining) and CD56 showed focal positivity in all
      cases with 5-10% of tumor cells displaying immunolabeling. All cases were
      negative for chromogranin and synaptophysin. All 18 cases displayed cytoplasmic
      and nuclear localization of beta-catenin protein. Similarly, E-cadherin protein
      was localized to the nucleus in all 18 cases, with loss of the characteristic
      membranous decoration of cells. CONCLUSION: This study is the first demonstration
      of aberrant nuclear localization of E-cadherin protein in solid pseudopapillary
      tumors of the pancreas. Whilst the exact mechanism is not know and nuclear E
      cadherin is not related to tumor aggression, this staining pattern may be of
      diagnostic value in concert with beta-catenin staining.

PMID- 17495359
TI  - Pancreas transplantation with histidine-tryptophan-ketoglutarate (HTK) solution
      and University of Wisconsin (UW) solution: is there a difference?
AB  - CONTEXT: In clinical pancreas transplantation the choice of preservation solution
      may have an impact on graft pancreatitis. Experience with histidine-tryptophan
      ketoglutarate (HTK) is still limited whereas University of Wisconsin (UW)
      solution is currently the preferred perfusate worldwide. OBJECTIVE: The aim of
      this study was to analyze our experience with HTK in pancreas transplantation.
      PARTICIPANTS: In a retrospective analysis, data from 95 primary simultaneous
      pancreas-kidney transplantations were reviewed. The use of HTK (n=48) and UW
      (n=47) solution was stratified into two groups. MAIN OUTCOME MEASURES:
      Patient/graft survival and early graft function were compared. RESULTS: No
      significant differences between 1, 3 and 12 month patient survival (HTK: 97.9%,
      97.9%, and 95.7% vs. UW: 95.7%, 89.4%, and 89.4%, respectively), and pancreas
      graft survival (HTK: 87.5%, 87.5%, and 85.4% vs. UW: 87.0%, 82.6%, and 82.6%,
      respectively) were detected. Higher values for peak lipase were observed on day 1
      in the HTK group (not reaching significance: P=0.131) whereas no differences were
      noted for amylase and C-reactive protein. CONCLUSIONS: HTK is clinically
      comparable to UW. Both solutions have been shown to be safe for pancreas
      preservation. Successful pancreas transplantation depends on many factors such as
      donor and recipient factors, but skilled organ procurement techniques, organ
      preservation, and transplant experience in this field is mandatory. The choice of
      organ preservation solution is only one point in this context.

PMID- 17495360
TI  - Carcinoma of the body of pancreas in evolution: an aggressive disease affecting
      younger patients?
AB  - CONTEXT: Pancreatic body carcinoma has a poor prognosis with advanced disease at
      presentation. Recent experience at multidisciplinary team (MDT) meetings suggests
      increasing prevalence. OBJECTIVE: Our aim was to determine if introduction of MDT
      meetings has affected the natural history of this disease. DESIGN: Retrospective
      diagnostic and survival data were collected from 1995 to 2006 at two large
      teaching hospitals, and divided into pre- and post 2003 groups (based on MDT
      introduction). PARTICIPANTS: Thirty-one patients with pancreatic body carcinoma
      (median age at diagnosis 72 years; range 43-87 years). RESULTS: Commonest
      symptoms at presentation were abdominal pain and weight loss. Eight patients
      (25.8%) were diagnosed pre MDT (median age 71.5 years, range: 60-87 years) and 23
      patients (74.2%) were diagnosed post MDT (median age 67 years, range: 43-85
      years; P=0.299 vs. pre MDT). There was a significantly (P=0.024) greater
      prevalence of more advanced tumours post MDT (stage IV: 15/23, 65.2%) than pre
      MDT (stage IV: 2/8, 25.0%). Neither tumour markers nor liver biochemistry
      differentiated tumour stage. Best supportive care was offered to 16 patients
      (51.6%) while 12 patients (38.7%) were suitable for chemotherapy: 2 out of 8 pre
      MDT (25.0%) and 10 out of 23 (43.5%) post MDT (P=0.433). For stage III tumours,
      post MDT patients tended to be younger (median 59 years vs. 74.5 years, P=0.042).
      Survival was not significantly increased after MDT introduction but chemotherapy
      offered significant survival benefit on multivariate analysis (P=0.042; hazard
      ratio: 0.39, 95% CI: 0.16-0.97). CONCLUSION: The trend is towards increased
      prevalence of pancreatic body cancer and more advanced disease at presentation.
      Chemotherapy was associated with a survival benefit, although the introduction of
      the MDT has not significantly altered disease management.

PMID- 17495361
TI  - A case of autoimmune pancreatitis associated with retroperitoneal fibrosis.
AB  - CONTEXT: Autoimmune pancreatitis is characterized by diffuse enlargement of the
      pancreas, diffuse irregular narrowing of the main pancreatic duct, severe
      lymphoplasmacytic infiltration and fibrosis of the pancreas. Retroperitoneal
      fibrosis may occasionally be associated with autoimmune pancreatitis. CASE
      REPORT: We report a 77-year-old man with autoimmune pancreatitis associated with
      retroperitoneal fibrosis. Abdominal ultrasonography and computed tomography
      demonstrated diffuse enlargement of the pancreas and a capsule-like rim.
      Furthermore, a retroperitoneal mass was recognized anterior to the abdominal
      aorta. Antinuclear antibody, IgG and IgG4 values were elevated. Therefore, this
      patient was diagnosed as having autoimmune pancreatitis associated with
      retroperitoneal fibrosis. We performed steroid therapy using prednisolone. After
      4 weeks, both IgG and IgG4 values decreased and both the swelling of the pancreas
      and also the retroperitoneal mass were obviously diminished. CONCLUSION: This is
      a rare case of autoimmune pancreatitis associated with retroperitoneal fibrosis.

PMID- 17495362
TI  - Peripancreatic tuberculous lymphadenopathy. An impostor posing diagnostic
      difficulty.
AB  - CONTEXT: Involvement of the peripancreatic lymph nodes by tuberculosis is rare
      and the clinical presentation varies. It can mimic cystic neoplasms of the
      pancreas. CASE REPORT: We report the case of a patient having peripancreatic
      tuberculosis who presented with fever, jaundice, supraclavicular lymphadenopathy
      and weight loss. Imaging and tumor markers also suggested a pancreatic
      malignancy. MRI helped to identify the peripancreatic lymph node involvement and
      biopsy of the supraclavicular lymph node clinched the diagnosis. CONCLUSION:
      Pancreatic and peripancreatic tuberculosis should be considered in the
      differential diagnosis of cystic lesions of the head of the pancreas.

PMID- 17495363
TI  - Adenosquamous carcinoma of the pancreas with clear cell and rhabdoid components.
      A case report.
AB  - CONTEXT: In as much as no such variant of this pancreatic tumour has been
      previously reported in the literature, we report an unusual case of an
      adenosquamous carcinoma of the pancreas characterized by clear cells and rhabdoid
      cells. CASE REPORT: A 75-year-old man presented with upper abdominal distention,
      dyspepsia, jaundice, and significant weight loss over a period of 3 months.
      Imaging of the abdomen showed a solid mass with cystic components in the region
      of the uncinate process of the pancreas. Endoscopic retrograde pancreatography
      showed mild to moderate dilatation of the intrapancreatic biliary tract and of
      the pancreatic duct, and a biliary stent was placed. The patient subsequently
      underwent a Whipple's procedure with curative intent. Histological evaluation of
      the pancreatic mass revealed an adenosquamous carcinoma displaying both clear
      cell and rhabdoid components. CONCLUSIONS: Assessing the predominant histology of
      pancreatic adenosquamous carcinoma variants such as those characterized by clear
      cells and rhabdoid cells may help select and improve upon therapies in this
      aggressive lesion.

PMID- 17495364
TI  - Autoimmune pancreatitis: medical and surgical management.
AB  - CONTEXT: Autoimmune pancreatitis is characterised by a lymphoplasmacytic
      infiltrate consisting in part of plasma cells that produce large amounts of IgG4.
      It can manifest as focal or diffuse enlargement of the pancreas with associated
      strictures of the pancreato-bilary tree giving rise to symptoms including
      abdominal pain, weight loss and obstructive jaundice; thus it can be extremely
      difficult in both presentation and investigation to distinguish from pancreatic
      carcinoma. Recent advances now facilitate preoperative diagnosis and effective
      medical management, including steroid treatment of autoimmune pancreatitis so
      preventing major surgical intervention. CASE REPORT: Two cases of autoimmune
      pancreatitis are described, each of which presented with obstructive jaundice and
      a relatively painless pancreatic mass, one with vascular involvement. They each
      had elevated serum CA 19-9 and ultimately required surgical exploration to
      definitely exclude malignancy before embarking on non operative treatment. The
      first case settled spontaneously while the second rapidly improved with steroid
      treatment. CONCLUSION: These two cases illustrate the difficulties in diagnosing
      this condition, the efficacy of steroid therapy and the role of surgical
      intervention in unresponsive cases or those where a diagnostic dilemma remains.

PMID- 17495365
TI  - Metastatic mucinous cystic adenocarcinoma of the pancreas presenting as Sister
      Mary Joseph's nodule.
AB  - CONTEXT: Sister Mary Joseph's nodule usually represents metastatic cancers from
      gastrointestinal malignancy including adenocarcinoma of the pancreas. Mucinous
      cystadenocarcinoma is a rare malignancy of the pancreas. However, pancreatic
      mucinous cystadenocarcinoma metastasized to Sister Mary Joseph's nodule is much
      rarer and has never been reported before. CASE REPORT: A 73-year-old Thai woman
      presented with progressive epigastric discomfort, severe back pain and
      significant weight loss over a 3 month period. Physical examination revealed
      right supraclavicular lymphadenopathy and Sister Mary Joseph's nodule at the
      umbilicus. A CT scan showed a large cystic lesion with internal septation at the
      pancreatic tail. Cyst fluid analysis revealed a brown mucoid fluid having high
      carcinoembryonic antigen and carbohydrate antigen 19-9 levels. Skin biopsy from
      the nodule confirmed the presence of metastatic mucinous cystadenocarcinoma.
      CONCLUSION: To our knowledge, this is the first report of pancreatic mucinous
      cystadenocarcinoma metastasized as Sister Mary Joseph's nodule.

PMID- 17495366
TI  - Positron emission tomography with 2-deoxy-2-[18f] fluoro-D-glucose in the
      detection of malignancy in intraductal papillary mucinous neoplasms of the
      pancreas.
AB  - A 79-year-old Indian male was admitted with upper abdominal discomfort of 1-year
      duration which was associated with loss of weight and appetite. Serum tumor
      markers, including carcinoembryonic antigen and carbohydrate antigen 19-9, were
      within normal limits. A computed tomographic scan demonstrated a cystically
      dilated and tortuous pancreatic duct measuring 1.9 cm, suggestive of an
      intraductal papillary mucinous neoplasm. Fusion positron emission
      tomography/computed tomography with 2-deoxy-2-[18F] fluoro-D-glucose positron
      emission tomography (FDG-PET/CT) which was subsequently performed confirmed a
      metabolically active focus within the pancreatic head mass with a standard uptake
      value (SUVmax) of 3.5 compatible with carcinoma. A total pancreatectomy was
      performed and the final histology demonstrated a main-duct type intraductal
      papillary mucinous neoplasm with a focus of high-grade dysplasia compatible with
      carcinoma-in-situ. These images illustrate the emerging utility of FDG-PET/CT in
      the preoperative detection of malignancy in intraductal papillary mucinous
      neoplasm.

PMID- 17495367
TI  - How to cure chronic pancreatitis: endoscopic or surgical approach?

PMID- 17495368
TI  - Stress in the workplace amongst medical professionals.

PMID- 17495369
TI  - Does immunoglobulin A nephropathy affect long-term graft outcome after kidney
      transplantation?

PMID- 17495371
TI  - Noncompliance with conventional medicine and use of complementary/alternative
      medicine.

PMID- 17495370
TI  - The validation of an instrument to diagnose depression: beyond the yes/no
      question.

PMID- 17495372
TI  - Bullying among trainee doctors in Southern India: a questionnaire study.
AB  - BACKGROUND: Workplace bullying is an important and serious issue in a healthcare
      setting because of its potential impact on the welfare of care-providers as well
      as the consumers. AIMS: To gauge the extent of bullying among the medical
      community in India; as a subsidiary objective, to assess the personality trait of
      the bullying victims. SETTINGS AND DESIGN: A cross-sectional, anonymous, self
      reported questionnaire survey was undertaken among a convenient sample of all the
      trainee doctors at a Government Medical College in Tamil Nadu, India. MATERIALS
      AND METHODS: A questionnaire, in English with standard written explanation of
      bullying was used. Basic information like age, sex, job grade and the specialty
      in case of Postgraduates (PGs) were also collected. STATISTICAL ANALYSIS: The
      results were subjected to descriptive statistical analysis and Chi-square test
      for comparison of frequencies. RESULTS: A total of 174 doctors (115 PGs and 59
      junior doctors), took part in the study with a cent percent response. Nearly half
      of the surveyed population reported being subjected to bullying. Nearly 54 (53%)
      of the men and 35 (48%) of women were subjected to bullying. Significant
      proportions (P < 0.0001) of medical personnel and paramedical staff bullied the
      PGs and junior doctors, respectively. More than 85 (90%) of bullying incidents
      went unreported. A significant (P < 0.0001) percentage of PGs and junior doctors
      revealed a personality trait towards bully. CONCLUSIONS: Workplace bullying is
      common among trainee doctors and usually goes unreported.

PMID- 17495373
TI  - Outcomes of renal transplantation in patients with immunoglobulin A nephropathy
      in India.
AB  - BACKGROUND: There is a paucity of data on the course of renal transplant in
      patients with immunoglobulin A (IgA) nephropathy (IgAN) from India. While the
      natural history of IgAN in the Indian context is rapidly progressive, the post
      transplant course remains speculative. AIM: To study the graft survival in renal
      transplant recipients whose native kidney disease was IgAN and the incidence and
      correlates of recurrent disease. SETTINGS AND DESIGNS: Retrospective case control
      study from a Nephrology unit of a large tertiary care center. MATERIALS AND
      METHODS: The outcomes of 56 transplant patients (58 grafts) with biopsy-proven
      IgAN and of 116 patients without IgAN or diabetic nephropathy, transplanted
      during the same period were analyzed. Correlates of biopsy-confirmed recurrent
      disease were determined. STATISTICAL ANALYSIS: Means were analyzed by Student's t
      test and Mann-Whitney test; proportions were determined by Chi-square analysis
      and graft survival curves were generated using the Kaplan-Meier. RESULTS: Five
      year graft survival for IgA patients was not significantly different from that in
      the reference group (90% and 79%, P = 0.6). During a mean follow-up of 42 months
      (range, 1-144), 28 event graft biopsies were required in 20 grafts of IgAN.
      Histological recurrence was diagnosed in five of the 20 available biopsies (25%)
      after a mean duration of 28 months. Recurrence did not correlate with donor
      status, HLA B35 and A2, recipient age, gender or immunosuppression. CONCLUSIONS:
      Renal transplantation is an appropriate treatment modality for IgA nephropathy
      patients with end-stage renal disease in India, despite the potential for
      recurrent disease. The posttransplant course is an indolent one when compared to
      the malignant pretransplant phase.

PMID- 17495374
TI  - Study of association between use of complementary and alternative medicine and
      non-compliance with modern medicine in patients presenting to the emergency
      department.
AB  - CONTEXT: Complementary and alternative medicines (CAMs) are extensively used by
      the public. Noncompliance is an important cause of therapy failure. AIM: This
      study was done to determine prevalence of emergency admission due to
      noncompliance with modern medicine following switching over to CAM and to
      identify any significant association for CAM use among noncompliers. SETTING AND
      DESIGN: This cross-sectional study was conducted in the emergency unit of a
      tertiary healthcare institute. MATERIALS AND METHODS: Demographic factors and
      system affected were compared between compliers and noncompliers. Prevalence,
      reasons and nature of noncompliance were determined. Age, gender, outcome,
      relation strength and potential preventability of noncompliance, precipitating
      and previous disease and noncompliant drugs were compared for significant
      association between CAM using and other noncompliers. STATISTICAL ANALYSIS:
      Student's 't' test, Chi square test and odds ratio were used. RESULTS: Of the 506
      patients interviewed 168 (33%) were noncompliant. In 160 (95%) patients
      noncompliance was due to under-dosing. Lack of knowledge and CAM use constituted
      144 (86%) noncompliance-related admissions. Thirty-three (7%) admissions were
      strongly related to noncompliance and CAM use. Age, gender, outcome, drug use and
      diseases except chronic obstructive pulmonary disease (COPD) and asthma showed no
      association while relation strength and potential preventability of emergency
      admission was less with CAM-using noncompliers. Noncompliance was observed for
      hypertension, diabetes, COPD and asthma, seizure disorder, tuberculosis and
      hemophilia besides hepatic and renal failure. The CAM noncompliers used CAM more
      for modern medicine incurable or unaffordable than curable diseases. CONCLUSION:
      Advice for regular treatment and frequent monitoring can decrease CAM use-related
      noncompliance admissions.

PMID- 17495375
TI  - Translation and validation of brief patient health questionnaire against DSM IV
      as a tool to diagnose major depressive disorder in Indian patients.
AB  - CONTEXT: Depression is frequently encountered in the primary care setting but is
      often unrecognized and hence untreated. There is a need for a uniform user
      friendly screening instrument for depression for primary healthcare personnel in
      India. AIMS: Translation and validation of the brief patient health questionnaire
      (BPHQ) as a screening tool for depression in major Indian languages. MATERIALS
      AND METHODS: This was a prospective study conducted at 18 sites, in psychiatric
      and general clinics. The English version of the BPHQ was translated into 11
      Indian languages. The translations were reviewed by experts and volunteers and
      proofread for the final translated BPHQ. The validation exercise included more
      than 3000 subjects. A psychiatrist and a psychiatry social worker / coordinator
      conducted the study under the supervision of the principal investigator. For each
      language, the presence or absence of major depressive disorder (MDD) as diagnosed
      with the help of a patient-completed BPHQ and the psychiatrist DSM-IV diagnosis
      was matched. The kappa coefficient was used as a measure of inter-observer
      agreement between the two diagnostic methods. RESULTS: Seven languages failed the
      primary validation exercise. These translations were reviewed and the updated
      versions, after proofreading were re-run for validation. The self-administered
      BPHQ was successfully translated and validated for diagnosis of MDD against DSM
      IV diagnosis made by a psychiatrist, in English, Hindi, Marathi oriya, Malayalam,
      Assamese, Gujarati, Kannada, Telugu, Bengali and Tamil. CONCLUSIONS: BPHQ is a
      simple, quick and reliable instrument, which facilitates rapid and accurate
      diagnosis of depression in the primary care setting in our country.

PMID- 17495376
TI  - Melioidosis presenting as genitourinary infection in two men with diabetes.
AB  - Melioidosis is an infectious disease caused by Burkholderia pseudomallei. It
      occurs predominantly in tropical regions. The manifestations are protean which
      include pneumonia, visceral abscesses, septic arthritis, osteomyelitis, acute
      suppurative and chronic granulomatous lesions with involvement of almost all
      organ systems. Fulminant sepsis is much more common and is associated with high
      mortality. Hence prompt recognition and early treatment is warranted. We report
      unusual presentations of urinary tract melioidosis in two diabetic men.

PMID- 17495377
TI  - Severe nitrofurantoin lung disease resolving without the use of steroids.
AB  - We report a case of an elderly woman who developed a severe, chronic pulmonary
      reaction to nitrofurantoin therapy that she had taken continuously for three
      years to prevent urinary tract infections. The patient was taking no other drug
      known to cause lung disease but the diagnosis was delayed by failure to recognize
      the association between nitrofurantoin and adverse drug reactions affecting the
      lung. When originally seen, the patient was unable to care for herself due to
      dyspnea. Bronchoscopy with biopsy ruled out other causes of her pulmonary
      disease. Immediate withdrawal of nitrofurantoin led to substantial, sustained
      improvement and disappearance of symptoms over several months without
      administration of corticosteroids. Nitrofurantoin toxicity should always be
      considered in any person taking that drug who develops bilateral infiltrates.

PMID- 17495378
TI  - Pott's puffy tumor following an insect bite.
AB  - Pott's puffy tumor, a feature of osteomyelitis of the frontal bone, is a rare
      entity, especially in adults. Sir Percival Pott originally described this
      condition as a complication of trauma to the frontal bone. This is also a
      recognized complication of fronto-ethmoidal sinusitis. We present a rare case of
      Pott's puffy tumor caused by an insect bite presenting initially as a preseptal
      cellulitis and explore its pathogenesis and management.

PMID- 17495379
TI  - Bilateral pleural effusions following central venous cannulation.
AB  - We describe a patient who developed bilateral pleural effusions as a delayed
      complication following central venous catheter insertion. Respiratory distress
      should not only raise the clinical suspicion of a pneumothorax but also of
      erosion and perforation of the central vein. The mechanism, diagnosis, management
      and prevention of this complication are discussed.

PMID- 17495380
TI  - Post-thoracentesis trapped lung.

PMID- 17495381
TI  - Adult mesenchymal stem cells: differentiation potential and therapeutic
      applications.
AB  - Adult mesenchymal stem cells (MSCs) are a population of multipotent cells found
      primarily in the bone marrow. They have long been known to be capable of
      osteogenic, adipogenic and chondrogenic differentiation and are currently the
      subject of a number of trials to assess their potential use in the clinic.
      Recently, the plasticity of these cells has come under close scrutiny as it has
      been suggested that they may have a differentiation potential beyond the
      mesenchymal lineage. Myogenic and in particular cardiomyogenic potential has been
      shown in vitro. MSCs have also been shown to have the ability to form neural
      cells both in vitro and in vivo, although the molecular mechanisms underlying
      these apparent transdifferentiation events are yet to be elucidated. We describe
      here the cellular characteristics and differentiation potential of MSCs, which
      represent a promising stem cell population for future applications in
      regenerative medicine.

PMID- 17495382
TI  - Polycystic ovary syndrome: a component of metabolic syndrome?
AB  - In 1935, Stein and Leventhal first described the polycystic ovary (PCO) as a
      frequent cause of irregular ovulation in women seeking treatment for
      subfertility. Although the initial management was surgical with wedge resection
      of ovary, the availability of radioimmunoassay and increased clinical use of
      ultrasound made it clear that many women had the ultrasound characteristics of
      PCO with or without the biochemical or clinical features of PCOS and therefore
      that PCO were not associated with a single syndrome. The association between
      increased insulin resistance and PCOS is a consistent finding in all ethnic
      groups. Obesity is a common factor in the majority of women with PCOS. It is
      postulated that a woman may be genetically predisposed to developing PCOS but it
      is only the interaction of environmental factors (obesity) with the genetic
      factors that results in the characteristic metabolic and menstrual disturbances.
      Weight loss, altered diet and exercise have been shown to be effective in the
      management of PCOS. Importance of early recognition, proper intervention, long
      term monitoring and health implications needs more concern.

PMID- 17495383
TI  - Exemestane: a milestone against breast cancer.
AB  - Rapid advances in the treatment of breast cancer, especially in the form of
      hormone therapy have truly increased the hope of longer and better disease-free
      survival for these patients. Exemestane, a third generation aromatase inhibitor
      has been extensively evaluated in metastatic as well as adjuvant therapy of
      breast cancer. It has also been evaluated for its safety profile, especially on
      bone and lipids. Exemestane provides hope to the patients with breast cancer both
      in early and metastatic disease. This review analyzes all the aspects of
      exemestane therapy.

PMID- 17495384
TI  - A new approach to the study of diet and risk of type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is a polygenetic disorder resulting from
      interaction of both hereditary and environmental factors. Diet is an important
      environmental factor in the development of T2DM. However, there existed
      inconsistent conclusions among previous studies. The validity of a study of
      associations between diet and diabetes depends on the method used in the study.
      Associations between individual nutrients/foods and T2DM have been explored even
      till today, but the controversy is still unsolved due to the limitations of the
      study methods such as interactions among nutrients. Emergence of analyses on
      dietary patterns and diabetes shows its popularity in the studies of associations
      of dietary patterns with T2DM, but only a few articles have been published. In
      this review, dietary-pattern-related studies since 1990 were identified by
      searching through Medline and PubMed in order to analyze methods used in the
      studies of diabetes. A dietary pattern approach was introduced as an alternative
      complementary way used to test associations of diet with risk of T2DM and the
      advantages of the studies of T2DM using this new approach are also explored. It
      is concluded that the dietary pattern approach shows its advantages over that
      using individual nutrients or foods in studies on associations between the diet
      and diabetes, but its reproducibility and validity for such effects, however,
      need to be further verified in different ethnic population-based on diverse
      eating habits. The long-term effects of a beneficial dietary pattern on T2DM also
      require clarifying in future studies.

PMID- 17495385
TI  - Ofloxacin-induced reversible arthropathy in a child.

PMID- 17495386
TI  - An unusual cause of colitis.

PMID- 17495387
TI  - Prenatal diagnosis of a case of pentalogy of Cantrell with spina bifida.

PMID- 17495388
TI  - Successful treatment of palmar-plantar erythrodysesthesia possibly due to
      temozolomide with dexamethasone.

PMID- 17495389
TI  - Blocked or delayed atrioventricular nodal conduction due to concealed conduction
      due to interpolated ventricular ectopics.

PMID- 17495390
TI  - Usefulness of prenatal detection of RhD typing by molecular analysis in Indians.

PMID- 17495391
TI  - Mania associated with interferon.

PMID- 17495392
TI  - Real-time analysis of secondary organic aerosol particles formed from cyclohexene
      ozonolysis using a laser-ionization single-particle aerosol mass spectrometer.
AB  - A real-time analysis of secondary organic aerosol (SOA) particles formed from
      cyclohexene ozonolysis in a smog chamber was performed using a laser-ionization
      single-particle aerosol mass spectrometer (LISPA-MS). The instrument obtains both
      size and chemical compositions of individual aerosol particles with a high time
      resolution (approximately 2 s at the maximum). Both positive and negative-ion
      mass spectra are obtained. Standard particles generated from dicarboxylic acid
      solutions using an atomizer were also analyzed. For both standard and SOA
      particles, the negative-ion mass spectra provided information about the molecular
      weights of the organic compounds in the particles, since the intense ions in the
      negative-ion mass spectra are mainly attributable to the molecular-related ions
      [M-H]-. It was demonstrated that the real-time single-particle analysis of SOA
      particles by the LISPA-MS technique can reveal the formation and transformation
      processes of SOA particle in smog chambers.

PMID- 17495393
TI  - Rapid and sensitive determination of the conversion of UV-cured acrylic ester
      resins by pyrolysis-gas chromatography in the presence of an organic alkali.
AB  - The double-bond conversion of UV-cured resins prepared from pentaerythritol
      triacrylate (PETA) was determined by pyrolysis-gas chromatography in the presence
      of an organic alkali, tetramethylammonium hydroxide (TMAH). The pyrogram of the
      uncured prepolymer compound, consisting of PETA and a photoinitiator, 2,2
      dimethoxy-2-phenylacetophenone, contained specific products reflecting the
      original acrylate structure, such as methyl acrylate (MA) and methyl ethers of
      pentaerithritol. Meanwhile, in pyrograms of the UV-cured PETA, the yields of MA
      considerably decreased. The double-bond conversions of the cured resins,
      irradiated with various UV dosages, were calculated based on the relative yields
      of MA among specific products in the pyrograms. The conversions determined by
      this approach were analyzed by comparing them with those estimated by Fourier
      transform infrared spectroscopy.

PMID- 17495394
TI  - Simultaneous measurements of K+ and calcein release from liposomes and the
      determination of pore size formed in a membrane.
AB  - The changes induced by biologically active substances in the permeability to K+
      and calcein of liposomes composed of egg phosphatidylcholine and cholesterol were
      measured simultaneously in order to rapidly screen the sizes of pores formed in a
      membrane, using different sized markers. The substances examined in the present
      study were classified into three types based on differences in the rates at which
      K+ and calcein were released. The first type released only K+, and included
      gramicidin A. The second type predominantly released K+, preceding the release of
      calcein, and included amphotericin B and nystatin. The third type, including
      antimicrobial peptides, such as gramicidin S, alamethicin, and melittin, and
      several membrane-active drugs, like celecoxib (non-steroidal anti-inflammatory
      drug), 1-dodecylazacycloheptan-2-one (named azone; skin permeation enhancer), and
      chlorpromazine (tranquilizer), caused the release of K+ and calcein
      simultaneously. Thus, the sizes of pores formed in a liposomal membrane increased
      in the following order: types one, two, and three. We determined the size more
      precisely by conducting an osmotic protection experiment, measuring the release
      of calcein in the presence of osmotic protectants of different sizes. The radii
      of pores formed by the second type, amphotericin B and nystatin, were 0.36 - 0.46
      nm, while the radii of pores formed by the third type were much larger, 0.63 -
      0.67 nm or more. The permeability changes induced by substances of the third type
      are discussed in connection with a transient pore formed in a lipid packing
      mismatch taking place during the phase transition of
      dipalmitoylphosphatidylcholine liposomes.

PMID- 17495395
TI  - Rapid and sensitive HPLC method for the simultaneous determination of paraquat
      and diquat in human serum.
AB  - A rapid and sensitive HPLC method for the simultaneous determination of paraquat
      and diquat in human serum has been developed. After deproteinization of the serum
      with 10% trichloroacetic acid, the samples were separated on a reversed-phase
      column, and subsequently reduced to their radicals with alkaline sodium
      hydrosulfite solution. These radicals were monitored with a UV detector at 391
      nm. This method permitted the reliable quantification of paraquat over linear
      ranges of 50 ng - 10 microg/ml and 100 ng - 10 microg/ml for diquat in human
      serum. The within- and between-day variations are lower than 2.3 and 2.2%,
      respectively. This technique was also utilized to determine the paraquat and
      diquat serum levels in a patient who had ingested herbicide (Prigrox L)
      containing paraquat and diquat.

PMID- 17495396
TI  - Cloud-point formation based on mixed micelles for the extraction,
      preconcentration and spectrophotometric determination of trace amounts of
      beryllium in water samples.
AB  - A cloud-point extraction process using a mixed micelle of the cationic surfactant
      cetyl pyridinium chloride (CPC) and non-ionic surfactant Triton X-114 to extract
      beryllium from aqueous solutions was investigated. The method is based on the
      color reaction of beryllium with Chrome Azurol S (CAS) in acetate buffer and the
      mixed micelle-mediated extraction of the complex. This complex was concentrated
      in a surfactant-rich phase after separation. The optimal extraction and reaction
      conditions (e.g. pH, reagent and surfactant concentrations, temperature,
      incubation and centrifuge times) were evaluated and optimized. Under the
      optimized conditions, the analytical characteristics of the method (e.g. limit of
      detection, linear range and preconcentration factor) were obtained. Linearity was
      obeyed in the range of 0.30 - 18 ng mL(-1) of beryllium and the detection limit
      of the method was 0.05 ng mL(-1). The interference effect of some cations and
      anions was also studied. The proposed method was successfully applied to the
      determination of beryllium in real water samples.

PMID- 17495397
TI  - Resonance light scattering of 1-hydroxypyrene-ethyl violet-anionic surfactant
      system and its analytical application.
AB  - A novel method for the rapid and sensitive analysis of 1-hydroxypyrene (1-OHP) in
      human urine has been developed that uses a resonance light scattering (RLS)
      technique. The assay was based on the interaction of ethyl violet (EV) with 1
      hydroxypyrene to form an ion-associate complex, which resulted in the enhancement
      of RLS intensity and the appearance of new RLS spectra. In the presence of
      anionic surfactant, the maximum RLS peak of the system was located at 396 nm at
      pH 8.0. Under the optimum conditions, it was found that the enhanced RLS
      intensity was directly proportional to the concentration of 1-hydroxypyrene in
      the range of 4.0 - 982 microg l(-1). The detection limit was 1.2 microg l(-1) and
      the recoveries of 1-hydroxypyrene were 92.8 - 102.3% (n = 6). The proposed method
      was successfully applied to the analysis of human urine samples. The results of 1
      hydroxypyrene were in agreement with those obtained by the method of high
      performance liquid chromatography.

PMID- 17495398
TI  - An improved method for the extraction of low molecular weight organic acids in
      variable charge soils.
AB  - Due to specific adsorption to variable charge soils, low molecular weight organic
      acids (LMWOAs) have not been sufficiently extracted, even if common extractants,
      such as water and 0.1 M sodium hydroxide (NaOH), were employed. In this work, the
      method for extracting LMWOAs in soils with 0.1 M NaOH was improved for variable
      charge soils; e.g. 1.0 M potassium fluoride (KF) with pH 4.0 was applied as an
      extractant jointed with 0.1 M NaOH based on its stronger ability to change the
      electrochemical properties of variable charge soils by specific adsorption. With
      the proposed method, the recoveries of oxalic, tartaric, malic, citric and
      fumaric acids were increased from 83 +/- 4, 93 +/- 1, 22 +/- 2, 63 +/- 5 and 84
      +/- 3% to 98 +/- 2, 100 +/- 2, 85 +/- 2, 90 +/- 2 and 89 +/- 2%, respectively,
      compared with NaOH alone. Simultaneously, the LMWOAs in Agri-Udic Ferrosol with
      field moisture were measured with a satisfactory result.

PMID- 17495399
TI  - Optimization of critical factors affecting the performance of an allergen chip
      for the analysis of an allergen-specific human IgE in serum.
AB  - A sensitive and multiplexed assay of allergen-specific human immunoglobulin E
      (IgE) is of great significance in the precise diagnosis of allergies. We report
      on the optimization of critical factors for chip-based analysis of IgE in human
      serum with a high reliability. Extracts of two mite species were used as model
      allergens, and were spotted onto a glass slide for the construction of an
      allergen chip. Respective allergen-specific IgE in human serum was analyzed by
      using biotinylated anti-human IgE and a streptavidin-Cy3 conjugate. Factors
      affecting the performance of the allergen chip were investigated and optimized.
      Especially, the effect of additives, the concentrations of biotinylated anti
      human IgE and the streptavidin-Cy3 conjugate, the serum dilution factor, and the
      concentration of allergen extract as a capturing agent were examined in detail.
      Under the optimized conditions, a chip-based analysis for sera from 43 patients
      revealed a reliable and reproducible diagnosis of respective allergies, showing a
      good correlation with a conventional CAP assay.

PMID- 17495400
TI  - An optode sensor for Cu2+ with high selectivity based on porphyrin derivative
      appended with bipyridine.
AB  - A porphyrin derivative (fluorophore) appended with bipyridine (ionophore) has
      been applied for preparation of a Cu2+-sensitive optical chemical sensor, which
      is based on fluorescence quenching of porphyrin derivative entrapped in a
      poly(vinyl chloride) membrane by the energy transfer process. The sensor exhibits
      a linear response toward Cu2+ in the concentration range 2.0 x 10(-8) - 1.0 x 10(
      5) M, with a working pH range from 6.0 to 8.0 and a high selectivity. The
      detection limit is 5 x 10(-9) M. The response time for Cu2+ is less than 5 min
      with concentrations lower than 5 x 10(-6) M. The optode can be regenerated using
      0.3 M EDTA (pH 9) and acetate buffer solution. The effect of the composition of
      the sensor membrane was studied, and the experimental conditions were optimized.
      The sensor has been used for direct determination of Cu2+ in water samples with
      satisfied results.

PMID- 17495401
TI  - A new spectrofluorometric probe for the determination of trace amounts of CoA in
      injection, human serum and pig livers.
AB  - A new spectrofluorometric method has been developed for the determination of
      trace amounts of coenzyme A (CoA). Using europium (Eu3+)-tetracycline (TC)
      complex as a fluorescent probe in the buffer solution of pH 6.80, CoA could
      remarkably enhance the fluorescence intensity of the Eu3+-TC complex at lambda =
      612 nm after adding H(5)IO(6) and the enhanced fluorescence intensity is in
      proportion to the concentration of CoA. Optimum conditions for the determination
      of CoA were also investigated. The dynamic range for the determination of CoA is
      6.08 x 10(-8) - 1.84 x 10(-5) mol L(-1) with detection limit of 4.62 x 10(-8) mol
      L(-1). This method is simple, practical and relatively free of interference from
      coexisting substances and can be successfully applied to determination of CoA in
      injection, human serum and pig liver samples. Moreover, the enhancement
      mechanisms of the fluorescence intensity in the Eu3+-TC system and the CoA-Eu3+
      TC system have been also discussed.

PMID- 17495402
TI  - Self-doped anthranilic acid-pyrrole copolymer/gold electrodes for selective
      preconcentration and determination of Cu(I) by differential pulse anodic
      stripping voltammetry.
AB  - Electropolymerization of anthranilic acid/pyrrole (AA/PY) at solid substrate
      electrodes (platinum, gold, and glassy carbon) gave stable and water-insoluble
      films under a wide range of pH. Combining high conductivity of the polypyrrole
      (PPY) and pH independence of the electrochemical activity of the self-doped
      carboxylic acid-substituted polyaniline allows us to prepare an improved
      functionalized PPY-modified electrode to collect and measure Cu(I) species. The
      differential pulse stripping analysis of the copper ions using a polyanthranilic
      acid-co-polypyrrole (PAA/PPY)-modified electrode consisted of three steps:
      accumulation, electrochemical reduction to the elemental copper and stripping
      step. Factors affecting these steps, including electropolymerization conditions,
      accumulation and stripping medium, reduction potential, reduction time and
      accumulation time, were systematically investigated. A detection limit of 5.3 x
      10(-9) M Cu(I) was achieved for a 7.0 min accumulation. For 12 determinations of
      Cu(I) at concentrations of 1.0 x 10(-8) M, an RSD of 3.5% was obtained. The log
      I(p) was found to vary linearly with log[Cu(I)] in the concentration range from
      7.0 x 10(-9) to 1.0 x 10(-5) M.

PMID- 17495403
TI  - Electrochemical determination of trace promethazine hydrochloride by a pretreated
      glassy carbon electrode modified with DNA.
AB  - A highly sensitive electrochemical biosensor for the detection of trace amounts
      of promethazine has been designed. Double stranded (ds)DNA molecules are
      immobilized onto a pretreated glassy carbon electrode (GCE(ox)) surface. The
      voltammetric behaviors of promethazine on DNA-modified electrode were explored by
      means of cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The
      promethazine gave rise to a pair of well-defined peaks, which appeared at E(pc) =
      52 mV and E(pa) = 96 mV (vs. Ag/AgCl) in 0.10 M acetate buffer (pH 5.0). The peak
      current was linearly enhanced with increasing the concentration of promethazine.
      The calibration was linear for promethazine over the range of 4.7 x 10(-10) to
      9.3 x 10(-9) M with a correlation coefficient of 0.999. The limit of detection
      (LODs) was 3.0 x 10(-10) M (S/N = 3). The modified electrode was applied to
      determine promethazine in human blood samples with satisfactory results.

PMID- 17495404
TI  - Modified carbon paste sensor for cetyltrimethylammonium ion based on its ion
      associate with tetrachloropalladate(II).
AB  - A comparative study was made between developed chemically modified carbon paste
      electrodes and PVC membrane electrodes for the cationic surfactant
      cetyltrimethylammonium bromide (CTAB). The carbon paste electrode modified with
      cetyltrimethylammonium-tetrachloropalladate(II) (CTA-TClP) provides a more
      sensitive and stable device than that shown by electrodes with an inner reference
      solution. The best performance was obtained by an electrode based on the paste
      containing 3.6 wt% CTA-TCIP, 1.8 wt% ethylhexadecyldimethylammonium bromide, 37.6
      wt% graphite and 57 wt% tricresyl phosphate. The sensor exhibited a Nernstian
      response for CTAB over a wide concentration range of 3.5 x 10(-7) to 1.0 x 10(-3)
      M with a detection limit of 2.0 x 10(-7) M between pH 2.7 and 8.2 with a fast
      response time of <or=15 s. The electrode showed excellent selectivity for CTAB
      over a large number of ions. Interferences caused by common cationic surfactants
      have been investigated in simulated mixtures containing high concentration levels
      of interfering surfactants, and the sensor was found to be tolerant against these
      compounds.

PMID- 17495405
TI  - Elimination of matrix effect and simultaneous determination of multi-components
      in complex systems by matrix coefficient non-linearity multivariate calibration
      based on single point response signals.
AB  - In order to deal with the matrix effect in the simultaneous determination of
      multi-components in a complex system, we have developed a novel method named
      matrix coefficient multivariate calibration method (MCMCM) for simultaneously
      determining n analytes in complex systems. The calibration models of n analytes,
      which are based on the experimental data of known samples, are first transformed
      into n linear equations, and then the equations are solved to obtain matrix
      calibration coefficients of the analytes in congeneric samples. In this way, the
      concentrations of n analytes in the unknown sample could be obtained easily and
      simultaneously by solving another n-variate linear equations with the help of the
      matrix calibration coefficients obtained-above. The method proposed in this work
      has been tested by voltammetry and atomic absorption spectrometry (AAS) with
      satisfactory results. On determining the elements such as Cu, Pb, Cd, Ni, Zn, Fe,
      Mn, Co, Ca, Mg, etc. in synthetic samples, the relative standard deviations
      (RSDs) of the results were 0.91 - 4.5%, and the recoveries were 95.8 - 105%. For
      actual samples, the RSDs and the recoveries were 1.5 - 6.9 and 92.0 - 110%,
      respectively.

PMID- 17495406
TI  - Cyclic voltammetry of the electron transfer reaction between
      bis(cyclopentadienyl)iron in 1,2-dichloroethane and hexacyanoferrate in water.
AB  - The electron transfer (ET) reaction between bis(cyclopentadienyl)iron(II)
      ([Fe(II)(C(5)H(5))2]) in 1,2-dichloroethane (1,2-DCE) and hexacyanoferrate redox
      couple ([Fe(II/III)(CN)6](4-/3-)) in water (W) at the interface has been studied
      by using cyclic voltammetry. The voltammetric results can be explained well by a
      theoretical equation for the so-called IT-mechanism, in which a homogeneous ET
      reaction between [Fe(C(5)H(5))2] (partially distributed from 1,2-DCE) and
      [Fe(CN)6](3-) takes place in the W phase and the resultant [Fe(C(5)H(5))2]+ ion
      is responsible for current passage across the interface. The forward rate
      constant of the homogeneous ET reaction, [Fe(C(5)H(5))2] + [Fe(CN)6](3-) =
      [Fe(C(5)H(5))2]+ + [Fe(CN)6](4-) in W phase, k(f)(IT), was determined to be (2.9
      +/- 2.2)x 10(10) M(-1) s(-1), which was in good agreement with k(f)(IT) = (3.2 +/
      2.0)x 10(10) M(-1) s(-1), which had been determined by using normal-pulse
      voltammetry.

PMID- 17495407
TI  - Development of an egg-white bioassay for monitoring biotin levels in urine and
      serum.
AB  - This article reports on the development of a simple and cost-effective bioassay
      for the detection of biotin in urine and serum, based on the very selective
      binding of avidin and biotin. Avidin was allowed to react without isolating it
      from egg white. Egg white was treated with the dye HABA, which binds to avidin.
      Upon subsequent treatment with biotin, HABA is released due to the high affinity
      of biotin to avidin. The amount of HABA released is proportional to the amount of
      biotin used.

PMID- 17495408
TI  - Flow injection chemiluminescence determination of imipramine in tablets, human
      plasma and urine samples based upon oxidation with singlet oxygen generated in N
      bromosuccinimide-hydrogen peroxide reaction.
AB  - Singlet oxygen generated in a reaction between N-bromosuccinimide and hydrogen
      peroxide was used for the chemiluminescence oxidation of imipramine. A strong
      chemiluminescence signal was observed when imipramine was mixed with N
      bromosuccinimide and hydrogen peroxide under an alkaline condition. The
      chemiluminescence signal was linearly dependent on the concentration of
      imipramine in the range of 0.01 - 1.0 mg/L. The detection limit was 0.005 mg/L
      imipramine and the relative standard deviation was 1.5% for a 0.4 mg/L imipramine
      solution in 11 repeated measurements. The proposed method was successfully
      applied to the determination of imipramine in tablets, human plasma and urine
      samples.

PMID- 17495409
TI  - Spectrophotometric determination of oxalate ion with N,N'-diethyl-N,N'-[[4,4'
      dihydroxy-1,1'-binaphthalene]-3,3'-diyl]bisbenzamide and copper(II).
AB  - A simple and rapid spectrophotometric method for the determination of oxalate ion
      was established by the fading of a colored complex between N,N'-diethyl-N,N'
      [[4,4'-dihydroxy-1,1'-binaphthalene]-3,3'-diyl]bisbenzamide and copper(II).
      Beer's law was obeyed in the concentration range of 0.1 - 2.0 microg cm(-3) for
      oxalate ion, with an effective molar absorptivity at 533 nm and the relative
      standard deviation being 8.0 x 10(3) dm(3) mol(-1) cm(-1) and 1.0% (n = 5),
      respectively. This proposed method has excellent reproducibility, and was applied
      to recovery tests of oxalate ion in tap water and human urine; the results were
      satisfactory. This is suggested that the method is based on the reaction of
      copper(II) to copper(I) with oxalate ion.

PMID- 17495410
TI  - Ion-interaction chromatography of several metallocyanide complexes stabilized by
      adding cyanide in a neutral mobile phase.
AB  - Standard solutions (at 10(-5) M levels) of Cu(I)- and Fe(II)-cyanide complexes
      were stabilized for at least 5 h using 0.5 mM cyanide solution (around pH 9) as a
      medium. Complexes of Cu(I)- and Fe(III)-cyanide also could be stabilized without
      any dissociation by adding 1 mM cyanide to an acetonitrile-water (18:82, v/v)
      mobile phase (pH 7.0) containing 10 mM tetra-n-propylammonium salt (TPA). Under
      the optimal conditions, the six complexes of Cu(I)-, Ag(I)-, Ni(II)-, Fe(II)-,
      Fe(III)- and Au(I)-cyanides were resolved from their mixtures within about 45
      min, with well-shaped chromatographic peaks.

PMID- 17495411
TI  - Precise determination of Pu isotopes in a seawater reference material using ID-SF
      ICP-MS combined with two-stage anion-exchange chromatography.
AB  - In order to obtain the precise Pu isotope composition of Irish Sea water
      reference material issued by the International Atomic Energy Agency (IAEA-381),
      we analyzed the activities of (239)Pu, (240)Pu and the atom ratio of
      (240)Pu/(239)Pu by a highly sensitive isotope dilution SF-ICP-MS method combined
      with two-stage chromatographic separation and purification. With a mean chemical
      yield of 65% for (242)Pu tracer, the experimentally established values for
      (239)Pu, (240)Pu and (239+240)Pu activities are in good agreement with the
      certified ones. For the (240)Pu/(239)Pu atom ratio, we obtain a value of 0.2315
      +/- 0.0008 with a high precision (RSD, 0.35%), which is much more precise than
      the information value of 0.22 +/- 0.03 (RSD, 13.6%) provided by the IAEA
      certification report. The precise determination of Pu isotopes in this seawater
      reference material will be useful for the validation of analytical methods for
      the study of radionuclides in the marine environment.

PMID- 17495412
TI  - SNP communications: coalition of toxicology and drug metabolism and
      pharmacokinetics.

PMID- 17495413
TI  - Mechanistic analysis for drug permeation through intestinal membrane.
AB  - For drug absorption, intestinal drug permeability's through both the paracellular
      and transcellular routes were analyzed. Absorption enhancers, such as sodium
      caprate (C10), decanoylcarnitine (DC) and tartaric acid (TA), increased the
      paracellular permeability of water-soluble, low lipophilic and poorly absorbable
      drugs by enlargement of tight junction (TJ) adhering to the intercellular
      portion; that is, expansion of the paracellular routes. C10 increased the
      intracellular calcium level to induce contraction of calmodulin-dependent actin
      filaments. Although DC also increased the intracellular calcium level, the action
      was independent of calmodulin, and thus the action mechanism of DC was considered
      to differ from that of C10. DC and TA decreased the intracellular ATP level and
      the intracellular pH, suggesting that intracellular acidosis increases the
      calcium level through decrease in ATP level followed by opening TJ. TA had no
      effect on Western blot analysis, but TA significantly inhibited excretion of
      rhodamine 123, one of the P-glycoprotein (P-gp) substrates, from the serosal to
      mucosal side, suggesting that TA increases the intestinal absorption of P-gp
      substrates, possibly by inhibiting the P-gp function without changing the
      expression of P-gp. During ischemia/reperfusion (I/R) injury during small
      intestine grafting, TJ opening and decrease in P-gp function simultaneously
      occurred. The in vitro model of I/R showed that lipid peroxidation is a trigger
      of the injury, and superoxide and iron ion participate in TJ opening and decrease
      in P-gp function. Colonic epithelial cells have the specific transcellular
      transport systems for lipopolysaccharide (LPS), one of which shows substrate
      specificity in the interaction with CD14 and/or that of TLR4. In the infective
      disease induced by LPS, the mucosal LPS sensitive transport capability was
      decreased and in the secretory direction, the receptor-mediated uptake mechanism
      disappeared. LPS taken up into the cells can be excreted by P-gp or mrp. The
      expression levels and function of the secretory transporters were considered to
      be increased in the infective condition. In conclusion, changes in TJ as the
      membrane structure and P-gp as the membrane function are important factors
      controlling intestinal membrane transport.

PMID- 17495414
TI  - P450 phenotyping of the metabolism of selegiline to desmethylselegiline and
      methamphetamine.
AB  - Although there is evidence in the literature of the participation of CYP2B6 in
      the metabolism of selegiline, it is not clear which other CYP isoforms contribute
      to its metabolism. The aim of this study was to investigate the P450 isozymes
      (CYPs) involved in the metabolism of selegiline to desmethylselegiline (DMS) and
      methamphetamine (MA) using four assays: incubation of selegiline with cDNA
      expressed CYPs, inhibition of DMS and MA formations in human liver microsomes by
      CYP-selective chemical inhibitors or CYP-specific antibodies, and correlation
      analysis. Correlation analysis, performed in a bank of 15 individual human liver
      microsomes, yielded correlation coefficients for DMS and MA formation of 0.769
      and 0.792, respectively, for CYP2B6 (p<0.0001) and 0.333 and 0.349, respectively,
      for CYP3A4 (p<0.05). These results were supported by chemical/specific antibody
      inhibition assays. The results of correlation analysis and chemical inhibition
      also indicated that CYP2A6 seems to play a small role in the metabolism of
      selegiline. These findings confirm that CYP2B6 plays a major role in the
      metabolism of selegiline and also suggest the involvement of CYP3A4 and CYP2A6.

PMID- 17495415
TI  - Pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration of
      ciprofloxacin for the treatment of respiratory infections.
AB  - The pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration
      of ciprofloxacin (CPFX) for the treatment of respiratory infections caused by
      pathogenic microorganisms resisting sterilization systems of alveolar macrophages
      (AMs) was evaluated by comparison with an oral administration. The time-courses
      of the concentration of CPFX in AMs and lung epithelial lining fluid (ELF)
      following intrapulmonary administration of CPFX solution to rats (200 microg/kg)
      were markedly higher than that following oral administration (10 mg/kg). The time
      course of the concentrations of CPFX in plasma following intrapulmonary
      administration was markedly lower than that in AMs and ELF. These results
      indicate that intrapulmonary administration is more effective in delivering CPFX
      to AMs and ELF, compared with oral administration, in spite of a low dose and it
      avoids distribution of CPFX to the blood. In addition, the antibacterial effects
      of CPFX in AMs and ELF following intrapulmonary administration were evaluated by
      pharmacokinetics/pharmacodynamics analysis. The concentration of CPFX in AMs and
      ELF-time curve (AUC)/minimum inhibitory concentration of CPFX (MIC) ratio and the
      maximum concentration of CPFX in AMs and ELF (Cmax)/MIC ratio were markedly
      higher than the effective values. The present study indicates that intrapulmonary
      administration of CPFX is an effective technique for the treatment of respiratory
      infections.

PMID- 17495416
TI  - Effect of Lactobacillus casei on the absorption of nifedipine from rat small
      intestine.
AB  - Lactobacillus casei Shirota strain (L. casei) has a modulating effect on the
      production of cytokines, which often play important roles in drug metabolism, in
      the inflamed intestinal mucosa. We evaluated the effect of L. casei administered
      orally in advance for 4 weeks on the absorption of nifedipine from the rat small
      intestine. The maximum concentration of nifedipine in plasma after administration
      into the intestinal loop (0.8 mg/kg) was significantly higher in L. casei-treated
      rats (3.26 microg/mL) than in those untreated rats (2.33 microg/mL) by 40%.
      Accordingly, the bioavailability of nifedipine was tended to be higher in the
      former, while the effect of L. casei on the disposition of intravenously
      administered nifedipine was negligible. We also found that the availability of
      nifedipine for the passage through the intestinal mucosa was significantly
      increased in L. casei-treated rats from the single-pass intestinal perfusion
      experiments. Therefore, it is likely that the exposure to nifedipine after its
      administration into rat intestine was increased by oral ingestion of L. casei due
      to an increase in absorption by increased intestinal availability (decreased
      metabolic extraction) during passage through the intestinal mucosa. This study
      has suggested that L. casei has some effect on the metabolic activity in the
      intestinal mucosa, though it seems to be only mild.

PMID- 17495417
TI  - Morphine glucuronosyltransferase activity in human liver microsomes is inhibited
      by a variety of drugs that are co-administered with morphine.
AB  - Morphine is an analgesic drug used for the treatment of acute and chronic pain
      syndromes for cancer patients. Glucuronidation is a major pathway of the
      elimination of morphine in humans. Morphine is metabolized to 3-glucuronide (no
      analgesic effect) and 6-glucuronide (more potently analgesic than morphine)
      mainly by UGT2B7. In the present study, we investigated the inhibitory effects of
      a variety of drugs on the morphine glucuronosyltransferase activities in human
      liver microsomes. Twenty-one drugs including anticancer drugs,
      immunosuppressants, analgesics, anticonvulsants, antidepressants, antipsychotic
      drugs were selected in this study, because they are frequently co-administered
      with morphine. We found that 10 out of 21 drugs, tamoxifen, tacrolimus,
      diclofenac, carbamazepine, imipramine, clomipramine, amitriptyline, diazepam,
      lorazepam and oxazepam extensively inhibited the morphine 3- and 6
      glucuronosyltransferase activities. Although some of the drugs are not substrates
      of UGT2B7, they would be potent inhibitors of UGT2B7. If patients receive
      morphine and these drugs simultaneously, the drug-drug interaction may change the
      levels of morphine and these glucuronides, resulting in altered analgesic
      efficacy and the risk of side effects. The results presented here will assist
      clinicians in choosing the proper drugs and/or dosages, and enable them to
      anticipate potential drug-drug interactions.

PMID- 17495418
TI  - Effect of ion suppression on judgment of enzyme inhibition and avoidance of error
      by utilizing a stable isotope-labeled probe substrate: example of CYP3A4
      inhibition with [13C4,15N] labeled midazolam as a substrate.
AB  - An advantage of using LC-MS(/MS) for in vitro CYP inhibition screening is that it
      does not require extensive sample preparation and chromatographic separation.
      Attention must be paid, however, to ion suppression effects on analytes caused by
      the test compound as well as endogenous compounds. In this study, we have shown
      the ion suppression of 1'-hydroxymidazolam (analyte) and dextrorphan (IS) by
      erythromycin, as an example, which may cause over- or underestimation of CYP3A4
      inhibition. To avoid this kind of effect, we proposed to use a stable isotope
      labeled substrate and determine labeled metabolites by using unlabeled authentic
      compounds of each metabolite. We showed that CYP3A4 activity was determined with
      high accuracy and precision by using stable isotope-labeled midazolam even in the
      presence of an ion suppressor at high concentrations in the samples. This method
      is useful not only for the CYP inhibition screening but also for testing drug
      candidates to predict changes in metabolite formation by the possible co
      administered drugs.

PMID- 17495419
TI  - Developmental changes of aldehyde oxidase in postnatal rat liver.
AB  - In this study, the developmental changes and variability of aldehyde oxidase in
      postnatal rat liver were examined. Postnatal day 1, 7 and 14 rats showed little
      or no liver aldehyde oxidase activity, as evaluated in terms of the activities
      for oxidation of benzaldehyde to benzoic acid, N-1-methylnicotinamide (NMN) to N
      1-methyl-2-pyridone-5-carboxamide (2-PY) and N-1-methyl-4-pyridone-3-carboxamide
      (4-PY), and methotrexate (MTX) to 7-hydroxymethotrexate (7-OH-MTX). However,
      these oxidase activities were markedly increased in liver cytosol from the rats
      after postnatal day 14. The activity was then maintained up to 6 weeks. The
      amounts of 2-PY and 4-PY formed from NMN were almost the same. The development of
      aldehyde oxidase activity toward benzaldehyde was closely correlated with that of
      oxidase activity toward NMN and MTX. The expression of aldehyde oxidase at
      postnatal day 14 was confirmed by Western blotting analysis. The density of bands
      of aldehyde oxidase was closely correlated with the oxidase activity toward
      benzaldehyde. The developmental changes of aldehyde oxidase activities during
      postnatal reflected the changes in the amount of the oxidase protein. Thus,
      aldehyde oxidase activity in rats rapidly increases from birth, reaching a
      plateau within 4 weeks, and is regulated by expression of the protein.

PMID- 17495420
TI  - Genetic polymorphism of bile acid CoA: amino acid N-acyltransferase in Japanese
      individuals.
AB  - In the present study, we identified three novel single nucleotide polymorphisms
      (SNPs), 147C>T in exon 2 (silent), 602G>C in exon 3 (Arg201Pro), and 1134C>T in
      exon 4 (silent), in the gene of bile acid CoA: amino acid N-acyltransferase
      (BAAT) by resequencing the entire coding region and the exon-intron junctions of
      100 Japanese individuals. The allelic frequencies were 0.005 for 147C>T, 0.095
      for 602G>C, and 0.015 for 1134C>T. The two known SNPs, 59G>A (Arg20Gln,
      rs1572983) and UTR1513G>A (rs2229594), were detected at a frequency of 0.500 and
      0.425, respectively. In the haplotype analysis for the 59G>A and 602G>C
      polymorphisms, the allelic frequency of 59G-602G, 59G-602C, 59A-602G and 59A-602C
      was 0.405, 0.095, 0.500 and 0.000, respectively. On the other hand, the allelic
      frequency of the nonsynonymous SNP 602G>C was 0.194 in a Caucasian population.

PMID- 17495421
TI  - Genetic variations of the ABC transporter gene ABCC3 in a Japanese population.
AB  - An ATP-binding cassette transporter, multidrug resistance-related protein 3
      (MRP3), is encoded by the ABCC3 gene. The MRP3 protein is expressed in several
      tissues, and functions as an efflux transporter for conjugated as well as
      unconjugated substrates. In this study, the 31 ABCC3 exons and their flanking
      introns were comprehensively screened for genetic variations in 89 Japanese
      subjects. Forty-six genetic variations, including 21 novel ones, were found: 8
      were located in the 5'-flanking region, 14 in the coding exons (8 synonymous and
      6 nonsynonymous variations), and 24 in the introns. Of these 46 variations, five
      novel nonsynonymous variations, 2221C>T (Gln741Stop), 2395G>A (Val799Met),
      2798_2799delAG (Gln933ArgfsX64), 3657C>A (Ser1219Arg), and 4217C>T (Thr1406Met),
      were found as heterozygous variations. The allele frequencies were 0.011 for
      Ser1219Arg and 0.006 for the other four variations. Gln741Stop induces a stop
      codon at codon 741. Gln933ArgfsX64 causes a frame-shift at codon 933, resulting
      in early termination at codon 997. Both variations result in loss of 6
      transmembrane helices (from the 12th to 17th helices) in the C-terminus and all
      regions of nucleotide binding domain 2. Thus, both variant proteins are assumed
      to be inactive. These data provide fundamental and useful information for
      pharmacogenetic studies on MRP3-transported drugs in Japanese.

PMID- 17495422
TI  - Three novel single nucleotide polymorphisms (SNPs) of CYP2S1 gene in Japanese
      individuals.
AB  - We analyzed all nine exons and exon-intron junctions of the CYP2S1 gene in 200
      Japanese individuals and identified the following three novel single nucleotide
      polymorphisms (SNPs): 4612G>A (Glu147Glu) in exon 3, 5478C>T (Leu230Leu) and
      5479T>G (Leu230Arg, CYP2S1*5A) in exon 5. The allele frequencies were 0.013 for
      4612G>A, 0.058 for 5478C>T, and 0.003 for 5479T>G. In addition, a known SNP
      1324C>G (Pro74Pro) was detected at a frequency of 0.300.

PMID- 17495423
TI  - Forty month follow-up of persistent and difficultly controlled acromegalic
      patients treated with depot long acting somatostatin analog octreotide.
AB  - The objective of the present study was to investigate the effects of octreotide
      long acting release (S-LAR) preparation on GH and IGF-1 serum concentrations and
      pituitary tumor size in patients with persistent and difficultly controlled
      acromegaly even after adjuvant irradiation and/or dopamine agonists. Thirty-three
      patients with active acromegaly (26 female and 7 male, mean age; 43.94 +/- 14.01
      SD years) were included in this study. Patients were evaluated at baseline and at
      6, 12, 30 and 40 months for GH, IGF-1, and GH response to OGTT and biliary
      ultrasonography. Sella MRI was performed at initial and at 40 months. All
      patients received 20 mg S-LAR. Afterwards, the dosage was titrated to improve
      individual GH response and reduction of IGF-1 into normal ranges. Basal serum IGF
      1 levels decreased from median: 530 microg/l [IQR: 420-600] to 340 microg/l [IQR:
      230-460] at 6 months (p = 0.01), to 400 microg/l [IQR: 222.4-600] at 12 months (p
      = 0.48), to 396 microg/l [IQR: 318-468] at 30 months (p = 0.49), to 482 microg/l
      [308-580] at 40 months (p = 0.47). Nadir GH levels in OGTT fell from 2.70 ng/ml
      [IQR: 1.35-6.90] to 1.60 ng/ml [IQR: 0.36-4.10] at 6 months (p = 0.03), to 0.31
      ng/ml [IQR: 0.18-0.65] at 12 months (p<0.0001), to 1.50 ng/ml [IQR: 0.83-4.00] at
      30 months (p = 0.398) and to 0.89 ng/ml [IQR: 0.58-1.35] at 40 months (p<0.0001).
      Initially, pituitary adenoma volume was median: 1.18 ml [IQR: 0.08-3.50] and it
      shrank to 0.21 ml [IQR: 0-2.1] at 40 months (p = 0.08). Gallstones were detected
      in 12 patients and six of them underwent cholecystectomy. S-LAR is an effective
      treatment regimen in reducing GH and IGF-1 concentrations and as well as in
      shrinking tumor volume in persistent and difficultly controlled acromegalic
      patients.

PMID- 17495424
TI  - TGF-beta-like transcriptional effects of thyroglobulin (Tg) in mouse mesangial
      cells.
AB  - TGF-beta-like activities of proteins unrelated to the cytokine could mimic its
      actions in fibrosis and cell proliferation. Thyroglobulin (Tg) has been
      identified as having a TGF-beta receptor (TGFbetaR)-binding activity and is
      deposited in the glomerulus in certain immune-complex diseases. The aim of the
      present study is to determine whether Tg can reproduce the transcriptional
      activity of TGF-beta1 in the mouse glomerular mesangial cell (MC), and to examine
      whether such activity is manifested through TGFbetaR. Real-time RT-PCR was
      employed to examine the effects of TGF-beta1 and bovine Tg on the expression of
      three genes (TGF-beta1, plasminogen activator inhibitor 1 [PAI-1], and Pax-8)
      regulated by TGF-beta1 in other cell types. In addition, a pentacosapeptide TGF
      beta1 antagonist, beta(1)(25) (41-65) was employed to determine whether the
      transcriptional activity of Tg was mediated through the TGF-beta binding site on
      the TGFbetaR. A 6h exposure to TGF-beta1 resulted in increased TGF-beta1 and PAI
      1 transcript, and a decrease in Pax-8. Similarly, a 6h exposure to Tg resulted in
      increases of about 5-fold in TGF-beta1 and PAI-1 mRNA and a decrease of 53% in
      Pax-8. In comparison with other proteins, Tg had the greatest positive effect on
      TGF-beta1 transcript levels. beta(1)(25) (41-65) significantly reduced the TGF
      beta1-, but not the Tg-induced changes in TGF-beta1, PAI-1 and Pax-8 transcript
      levels. We conclude from these studies that Tg possesses a TGF-beta-mimetic
      transcriptional activity in the MC that is not mediated by its binding to
      TGFbetaR. These results suggest that Tg and other proteins could initiate
      glomerular injury by reproducing the actions of TGF-beta1 in the mesangial cell.

PMID- 17495425
TI  - Investigation of mRNA expression for secreted frizzled-related protein 2 (sFRP2)
      in chick embryos.
AB  - The roles of secreted frizzled-related protein 2 (sFRP2) in organ development of
      vertebrate animals are not well understood. We investigated expression of sFRP2
      during embryogenesis of Arbor Acre broiler chicken eggs. Expression of sFRP2 was
      detected in the folds and lateral layer of developing brains. The sFRP2 signals
      in the developing eye were marked as a circle along the orbit. In younger embryos
      on days 3-6, the sFRP2 signals were consistent with growth of the sclerotome,
      suggesting that sFRP2 may be associated with somite development. Furthermore,
      with the exception of bones, sFRP2 mRNA was detectable in the interdigital tissue
      of embryos older than eight days as the limbs matured. This revealed that sFRP2
      might play a role in myogenesis. In situ hybridization was also used to analyze
      the expression of sFRP2 in day 3-10 chick embryos. Signals were expressed in the
      gray matter of the developing brain coelom, including the optic lobe,
      metencephalon, myelencephalon, mesencephalon and diencephalon. The developing
      eyes contained an intercellular distribution of sFRP2 in the pigmented layer of
      the retina and photoreceptors. Furthermore, sFRP2 was expressed in the mantle
      layer of the neural tube and notochord. Based on these findings, it seems
      reasonable to suggest that sFRP2 may play an active role in embryogenesis,
      especially in development of the neural system, eyes, muscles and limbs.

PMID- 17495426
TI  - Dyspnea and symptom amplification in asthma.
AB  - BACKGROUND: The severity of a patient's asthma and the intensity with which he
      describes his dyspnea do not correlate. OBJECTIVES: There is an indirect
      relationship between airway function in asthma and the intensity of dyspnea; this
      relationship is found only when the measure of a patient's general tendency to
      exaggerate the intensity of any somatic symptom is considered simultaneously.
      METHODS: Lung function, including spirometry (forced expiratory volume in 1 s,
      FEV(1)) and plethysmography (airway resistance, R(aw)), dyspnea (Borg scale
      score) and the tendency to exaggerate (the somatosensory amplification scale
      score, SSAS) have been quantified in 42 stable asthmatic patients. RESULTS: There
      was no correlation between the Borg score and any spirometric or plethysmographic
      measure in these subjects. By contrast, there was a moderate correlation between
      the Borg score and the SSAS (r = 0.36, p = 0.03). However, when FEV(1) or R(aw)
      (abscissa) and Borg scores (ordinate) were converted to residuals, there was a
      moderate correlation between the residuals and the SSAS score (for FEV(1), r =
      0.33 and p = 0.05; for R(aw), r = -0.36 and p = 0.03). CONCLUSION: A physician
      may make a reasonable estimate of an asthmatic patient's lung function from the
      intensity of his complaint only if he - the physician - considers the patient's
      tendency to symptom amplify as well.

PMID- 17495427
TI  - Differential regulation of Toll-like receptor 4 gene expression in renal cells by
      angiotensin II: dependency on AP1 and PU.1 transcriptional sites.
AB  - BACKGROUND: Toll-like receptor 4 (TLR4) is involved in the sensing of
      lipopolysaccharide and, therefore, plays a central role in innate immune
      responses to gram-negative bacteria. Interestingly, TLR4 expression occurs within
      the kidney. We have previously demonstrated that angiotensin II (ANG II)
      upregulates TLR4 expression on mesangial cells. However, the factors controlling
      transcriptional activation of the Tlr4 gene in mesangial cells are not known, and
      the specificity of this response for other renal cells is unclear. METHODS:
      Cultured murine proximal tubular cells (mouse cortical tubule cell line; MCT
      cells), murine mesangial cells (MMCs), and murine podocytes were treated with ANG
      II. The expression of ANG II receptor mRNA and TLR4 mRNA and protein was
      determined by polymerase chain reaction and Western blotting. The transcriptional
      activity of wild-type and mutant mouse TLR4 promoter reporter constructs was
      determined upon transient transfection of the three cell types. RESULTS: Although
      MMCs, podocytes, and syngeneic proximal MCT cells similarly expressed ANG II
      receptors, ANG II stimulated TLR4 mRNA and protein expression in MMCs and
      podocytes only. A mouse TLR4 promoter construct (-518/+129), previously shown to
      contain all important transcriptional regulatory elements in various cell types,
      was activated by ANG II in MMCs and podocytes, but not in MCT cells. Mutation of
      a proximal PU.1-binding consensus site or an AP1 site abolished ANG-II-mediated
      transcriptional activation of the TLR4 promoter. Finally, basal transcription of
      the Tlr4 gene depended in all three cell lines on an intact AP1 site and
      additionally on the proximal PU.1 site in MMCs. CONCLUSIONS: ANG II stimulates
      TLR4 transcription through AP1 and PU.1 sites in a cell-specific manner. Since
      the intrarenal ANG II concentrations are enhanced in many pathophysiological
      situations, ANG-II-stimulated transcription of TLR4 on MMCs and podocytes may
      contribute to renal inflammation.

PMID- 17495429
TI  - Prevalence of nondiabetic renal disease in diabetic patients.
AB  - BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease
      in the USA, yet most patients with type 2 diabetes mellitus are not formally
      evaluated with a renal biopsy. Our aim was to evaluate the prevalence of
      nondiabetic renal disease (NDRD) in patients with type 2 diabetes mellitus to
      determine common clinical indicators suggestive of NDRD. METHODS: A retrospective
      analysis was performed on biopsy reports of patients who had undergone native
      renal biopsy between January 1, 1995, and December 31, 2005. RESULTS: After
      exclusion of 57 patients, 233 patients with DM2 were included in our analysis.
      Mean age at the time of biopsy was 58.1 +/- 13.7 years, and 53.0% of the study
      population were male. There were 124 cases (53.2%) with a pathologic diagnosis of
      NDRD, 64 (27.5%) with pure diabetic glomerulosclerosis (DGS) and 45 (19.3%) with
      concurrent NDRD and DGS (CD). Patients with NDRD tended to be younger than those
      with DGS and had significantly less associated diabetic retinopathy. Focal
      segmental glomerulosclerosis was the most common lesion found in patients with
      NDRD and accounted for 21.0% of all NDRD, followed by minimal-change disease
      (15.3%). IgA nephropathy (15.6%) and membranous glomerulonephritis (13.3%) were
      the most prevalent lesions found in patients with CD. CONCLUSIONS: The high
      prevalence of NDRD found in our population underscores the need for clinicians to
      consider renal biopsy in diabetic patients with an atypical clinical course,
      since additional disease-specific therapies may be helpful for this subset of the
      population.

PMID- 17495428
TI  - Hyperthermia alters kidney function and renal scintigraphy.
AB  - BACKGROUND/AIM: Fever can be caused by different reasons such as environmental
      conditions, acute rejection after kidney transplantation and bacterial diseases
      including kidney and urinary tract infections. The present study represents a
      novel idea of investigating the direct effect of body temperature elevation on
      kidney function to determine whether hyperthermia alters the kidney function
      transiently leading to inaccurate findings and possible misinterpretation of the
      radionuclide (99mTc-MAG-3) renography studies. METHODS: Renography studies were
      performed on New Zealand White rabbits weighing approximately 3-3.5 kg. Each
      rabbit was inject with 48.1 MBq (1.3 mCi) technetium-99m-mercaptoacetyltriglycine
      (99mTc-MAG-3). Studies were acquired using a gamma camera equipped with a low
      energy, high-resolution collimator interfaced with a computer. Dynamic images
      were acquired as 2-s frames for the first 1 min and every 30 s for the next 30
      min on a matrix of 64 x 64. Regions of interest were drawn over the whole
      kidneys. Radioactivity time curves were generated from the regions of interest.
      Time to peak activity (Tmax), time from peak to 50% activity (T1/2), and the
      uptake slope of each kidney were calculated from the renograms. Three days later
      the same protocol was repeated for the same rabbit but with a higher body
      temperature by 2 degrees C. Then it was repeated with a higher body temperature
      by 3 degrees C, then 4 degrees C with the same interval period. Blood pressure
      was measured using a catheter inserted into the femoral artery connected to a
      Lectromid recorder at normal temperature and during increasing the temperature by
      2, 3 and 4 degrees C. Renal blood flow was also measured via the renal artery
      using an electromagnetic blood flow sensor connected to a flowmeter. Creatinine
      and blood urea nitrogen (BUN) in blood were measured in control and hyperthermic
      rabbits. RESULTS: During hyperthermia the experimental curves shifted to the
      right of the control curves indicating that there was a delayed renal uptake of
      99mTc-MAG-3 and clearance of radioactivity. This delay was proportional to body
      temperature. Calculated averages were: Tmax 1.6 +/- 0.1, 2.8 +/- 0.3, 8.8 +/- 1,
      15 +/- 4 min; T1/2 2.77 +/- 0.2, 3 +/- 0.4, 8.9 +/- 1.1, 20 +/- 3.4 min, and
      perfusion index 190 +/- 5, 201 +/- 4, 218 +/- 7, 224 +/- 9 of control and
      hyperthermic (elevation of temperature 2, 3, and 4 degrees C) rabbits,
      respectively (n = 6; p < 0.05). Mean arterial pressure and renal blood flow did
      not significantly change during hyperthermia. Creatinine and BUN were
      proportionally elevated to high temperature. CONCLUSIONS: Our results indicate
      that hyperthermia causes a transient alteration in the function of the kidney and
      scintigraphic pattern on radionuclide renography. Radionuclide renography studies
      may be performed at normothermic temperature since interpretation at higher body
      temperature could lead to misleading results, and temperature should be checked
      and recorded for single and follow-up radionuclide renography studies.

PMID- 17495430
TI  - Pathogenesis of IgA nephropathy.
AB  - IgA nephropathy is generally considered to be an immune-complex-mediated or
      aggregated (polymerized) IgA (IgA1)-mediated glomerulonephritis. Since the
      pathogenesis of IgA nephropathy is still obscure, it is important to determine
      the initiation and progression of this disease using the spontaneous animal
      model. The ddY mouse strain can serve as a spontaneous animal model for IgA
      nephropathy. Genetic factors are considered to be involved in the initiation and
      progression of IgA nephropathy. It has been hypothesized that susceptibility
      genes for IgA nephropathy can be detected by a genome-wide scan using this model.
      The peak marker D10MIT 86 on chromosome 10 is located on the region syntenic to
      human 6q22-23 with IGAN1, which is responsible for familiar IgA nephropathy.
      There are several developmental and/or exacerbating factors in this disease.
      Among them, the loss of glomerular epithelial cells (podocytes) and interstitial
      mast cell infiltration are important factors for progression of
      glomerulosclerosis and tubulointerstitial injury in patients with IgA
      nephropathy.

PMID- 17495431
TI  - Treatment for IgA nephropathy.
AB  - The Committee on IgA nephropathy in Japan has published new clinical guidelines
      (2nd edition) for the diagnosis and treatment of patients with this disease. The
      nonspecific therapeutic approach involves a reduction of dietary intake of
      protein in patients with IgA nephropathy who have developed renal failure. At
      present, the most important therapeutic goal in patients with IgA nephropathy is
      the control of hypertension. It has been assumed that removal of tonsillar
      tissues might reduce the production of polymeric IgA and decrease the frequency
      of renal parenchymal damage resulting from episodes of macroscopic hematuria and
      proteinuria. Although there have been no randomized controlled trials (RCT) of
      tonsillectomy, these are necessary to determine the efficacy of tonsillectomy in
      patients with IgA nephropathy.

PMID- 17495432
TI  - International IgA nephropathy network clinico-pathological classification of IgA
      nephropathy.
AB  - There is no international consensus for the pathological or clinical
      classification of IgA nephropathy (IgAN). This has limited international
      comparisons between outcome studies which use different histological
      classifications, and made it more difficult to identify appropriate patients to
      enter into clinical intervention trials, as well as making it harder to choose
      appropriate therapy in individual patients. The International IgA Nephropathy
      Network (www.igan-world.org), working with members of the Renal Pathology
      Society, has established an international working group which is developing a
      consensus classification. Agreement has been reached on definitions of
      pathological features, and the consistency of scoring these features has been
      tested by pathologists around the world. Pathological features are now being
      scored in biopsies from large cohorts of patients from many parts of the world in
      whom sequential clinical information is available. From the integrated analysis
      of these clinical and pathological features, a clinico-pathological
      classification will be proposed which will be further refined and tested in
      additional cohorts of patients. The goal is to establish a reproducible and
      clinically effective classification which will gain worldwide acceptance for use
      in clinical practice and research.

PMID- 17495433
TI  - IgA nephropathy: a clinical overview.
AB  - Our understanding of the clinical aspects of IgA nephropathy (IgAN) has advanced
      since the 10th International Symposium on IgA Nephropathy in 2004. In this review
      we discuss new developments in areas of familial IgAN, the emerging field of
      biomarkers, and prognostic features. Familial disease continues to account for a
      significant number of newly diagnosed patients with IgAN. These patients have
      clinical manifestations and long-term outcomes similar to those of patients with
      sporadic disease. Characterization of the IgAN1 gene linked to IgAN in some
      Italian and American multiplex families has remained elusive. Other multiplex
      IgAN pedigrees have shown no linkage to any locus. With advances in technology to
      better measure and characterize polypeptides in small concentrations, the area of
      biomarkers has generated substantial interest since 2004. New potential disease
      specific biomarkers of IgAN include the IgA1 neoepitope at the threonine228
      and/or serine230IgA1 hinge-region residues, serum levels of galactose-deficient
      IgA, and urinary IgA-IgG immune complexes. Other investigators have used
      proteomic approaches to find panels of urinary polypeptides (many of which have
      not been sequenced) that discriminate patients with IgAN from normal healthy
      controls as well as patients with various other proteinuric renal diseases. These
      or other related findings may provide the necessary tools to better classify
      phenotypes in multiplex pedigrees and to improve monitoring of disease
      progression or response to therapy.

PMID- 17495434
TI  - Angiotensin antagonists and fish oil for treating IgA nephropathy.
AB  - In IgA nephropathy (IgAN), ACE inhibitors (ACE-I) and angiotensin receptor
      blockers (ARB) are beneficial against hypertension, and their anti-proteinuric
      effect has been clearly demonstrated. However, sub-analyses of IgAN patients
      enrolled in large studies failed to prove a benefit against progression to renal
      failure. The European Community Biomed Concerted Action - a placebo-controlled
      randomized controlled trial begun in 1995 - in children and adults (9-35 years
      old) with proteinuria > 1 < 3.5 g/day/1.73 m(2) and normal or moderately reduced
      renal function proved the significant benefit of ACE-I on progression of kidney
      disease. The combination of ACE-I and ARB in proteinuric normotensive IgAN
      patients showed greater antiproteinuric effect and the COOPERATE trial also
      reported a superior effect of combination therapy in protecting against renal
      function deterioration. Treating IgAN with fish oil has a good rationale for
      renal inflammation as well as for prevention of cardiovascular morbidity.
      However, the published reports gave conflicting conclusions and also very recent
      data did not show significant benefits. In conclusion, ACE-I and ARB have a
      definite role in treating IgAN, particularly the hypertensive and proteinuric
      forms. These patients should be treated to target BP to <130/70 mm Hg and
      proteinuria <0.5 g/day.

PMID- 17495435
TI  - Treatment of IgA nephropathy: corticosteroids, tonsillectomy, and mycophenolate
      mofetil.
AB  - Previous studies exploring the potential of glucocorticoid therapy on proteinuria
      and renal survival of patients with IgA nephropathy (IgAN) indicate that
      corticosteroid therapy is recommended if the patients show a moderate degree of
      proteinuria and their creatinine clearance exceeds 70 ml/min, although these
      studies, most of which are not prospective or randomized, have not provided
      conclusive results. Recently, Pozzi et al. demonstrated that treatment with
      glucocorticoids for 6 months significantly improved renal survival and
      proteinuria for 10 years of follow-up. A recent meta-analysis by Samuels et al.
      supports the use of corticosteroids in reducing proteinuria and preventing
      progression to end-stage renal disease. Increasing attention has been drawn to
      the role of tonsillectomy in the longterm prognosis of IgAN. The notion that
      tonsillectomy not only helps to prevent episodic macroscopic hematuria in the
      short-term but also gives long-term renal protection in IgAN is supported by two
      large retrospective studies from Japan. A study of 329 patients with IgAN by
      Hotta et al. found that tonsillectomy plus high-dose methylprednisolone was
      identified as one of the independent variables in predicting remission of
      clinical findings and lack of renal progression. Moreover, Xie et al. have
      reported that, for 20 years of follow-up, renal survival was significantly better
      in IgAN patients who underwent tonsillectomy than those who did not undergo the
      procedure. However, the role of tonsillectomy in the long-term prognosis of IgAN
      remains unclear, since it has not yet been tested in a controlled randomized
      trial. The role of mycophenolate mofetil (MMF) in IgAN has been examined in four
      major trials. Two prospective randomized studies report no benefit from MMF. The
      remaining two studies showed a greater reduction of proteinuria in patients
      treated with MMF compared to prednisone or placebo. In both studies, however, MMF
      did not effectively modify the progressive course of the disease. Thus, despite
      promising results in large randomized controlled trials in lupus nephritis, the
      evidence for the use of MMF in IgAN is inconclusive.

PMID- 17495436
TI  - Interpretation of renal biopsies in IgA nephropathy.
AB  - The renal biopsy is essential for the diagnosis of IgA nephropathy. It should
      also be possible to derive important information from the biopsy about prognosis
      and likely response to treatment. Biopsy features that are associated with
      progression to end-stage renal disease are glomerulosclerosis and
      tubulointerstitial scarring, marked crescent formation and marked arteriolar
      hyalinosis. However, with our present classification systems the renal biopsy
      adds little over and above clinical features in predicting outcome. It may be
      possible to improve the predictive value of the renal biopsy by adopting the
      following recommendations in developing new classifications: (1) looking at the
      ability of the biopsy to predict changes in renal function in the short term
      after biopsy rather than prediction of progression to end stage renal disease;
      (2) examining subgroups of patients where the biopsy is likely to be most
      informative; (3) distinguishing the effects of reversible and irreversible
      changes particularly with regard to response to treatment; (4) ensuring
      uniformity of definitions between pathologists, and (5) paying attention to small
      lesions and considering including additional biopsy features. The most important
      role for the renal biopsy in the future is likely to be in predicting response to
      therapy rather than predicting progression to end-stage renal disease.

PMID- 17495437
TI  - Altered expression of lymphocyte homing chemokines in the pathogenesis of IgA
      nephropathy.
AB  - Defective adaptive humoral immune responses to mucosal immunogens, but intact
      systemic responses, are increasingly recognized in patients with IgA nephropathy
      (IgAN). Reduced expression of IgA+, J chain+ cells in the gut lamina propria,
      with collateral increases in these cells in the marrow, is also documented. Thus,
      there seems to be a derangement in a 'mucosa-marrow axis' in IgAN patients.
      Recent evidence indicates that chemokines regulate the localization of B cells
      and their progeny into respiratory and intestinal lamina propria, and into other
      lymphoid organs as well. Particularly, secretory epithelial cells express the
      chemokine CCL28, whereas small bowel cells uniquely express CCL25. Extramucosal
      sites preferentially express CXCL12, CXCL13 and/or CXCL16. Reciprocally,
      plasmablasts committed to IgA synthesis ubiquitously express the receptor (CCR10)
      for CCL28, and a subset also express the receptor (CCR9) for CCL25; neither of
      these is present on cells committed to IgG or IgM synthesis. Herein, the
      potential contributions of virally induced innate responses to defective mucosal
      immunity and overproduction of oligomeric IgA in the marrow and tonsils will be
      reviewed, particularly with respect to the influence that viral infection exerts
      upon the expression of selected chemokine and receptor pairs. The ramifications
      for pathogenesis of IgAN will be considered.

PMID- 17495438
TI  - IgA nephropathy: current views of immune complex formation.
AB  - Characteristic features of IgA nephropathy (IgAN) include IgA1-containing immune
      complexes (IC) in the circulation, urine, and renal mesangium. IC contain IgA1
      deficient in hinge region-associated galactose (Gal) and antibodies specific for
      antigenic determinants present on the hinge region. The biological effects of IC
      are primarily related to their molecular size and composition: when added to a
      culture of human mesangial cells, large IC exhibit a proliferative effect while
      small complexes are inhibitory. These activities have been observed using IC
      obtained from sera of IgAN patients or generated in vitro. Specifically, various
      preparations of human IgA1 with modified glycan moieties formed IC in vitro when
      incubated with sera from IgAN patients or healthy individuals, cord blood serum,
      or tissue culture supernatants of EBV-immortalized peripheral blood B cells
      secreting IgG. Interestingly, IgG antibodies specific for the IgA1 Gal-deficient
      hinge region are commonly found in sera of hominoid as well as non-hominoid
      primates and many other vertebrate species, and suggest the evolutionary
      uniqueness of the human IgA1 hinge region. Because of the molecular defect in
      IgA1 glycosylation and its subsequent recognition by naturally-occurring
      antibodies, experimental approaches that diminish or prevent formation of large
      immunostimulatory IC should be further explored.

PMID- 17495439
TI  - Pathogenic role of IgA receptors in IgA nephropathy.
AB  - The pathogenesis of IgA nephropathy (IgAN) involves the deposition of aberrant
      glycosylated IgA1 and/or of IgA1-immune complexes (IC) in the glomerular
      mesangium. The mechanisms involved in the generation of IgA1-IC and how they are
      deposited in the mesangium are just emerging. We propose a model whereby two
      types of IgA receptors participate in sequential steps to promote the development
      of IgAN, with soluble FcalphaRI (CD89) being initially involved in the formation
      and/or amplification of the size of circulating IgAIC and, subsequently,
      transferrin receptor (CD71), in mediating mesangial deposition of nephritogenic
      IgA1-IC. Activation of transmembrane FcalphaRI associated with FcRgamma adaptor
      following interaction with IgA-IC is involved in aggravation of IgAN through
      induction of leukocyte infiltration. Taken together, understanding of the role of
      IgA receptors in physiology and physiopathology will open new avenues for
      therapeutic strategies in IgAN.

PMID- 17495440
TI  - The mucosa-bone-marrow axis in IgA nephropathy.
AB  - Large numbers of studies have demonstrated that abnormal humoral and cellular
      immunity may contribute to the pathogenesis of IgA nephropathy. On the other
      hand, clinical evidence indicates that bone marrow cells and mucosal immunity may
      also play a key role. Based on these findings, impaired immune regulation in the
      'mucosa-bone-marrow axis' has been postulated in IgA nephropathy patients.
      However, the underlying mechanisms still remain unclear. This is mainly due to
      difficulties in the clinical approach to the complicated immune system.
      Therefore, appropriate animal models are required. We recently established
      several useful animal models. Using these models, our group is approaching
      underlying mechanisms in which bone marrow and mucosal cells interrelate and
      finally induce this disease. Up to now, results from these models and its
      clinical feedback have suggested that mucosal IgA responses to antigens may be
      altered by Th2-biased background or dysregulation of innate immunity in this
      disease. This abnormal mucosal IgA immune system may result in failure of mucosal
      antigen elimination and thus increases in memory cells in the bone marrow.

PMID- 17495441
TI  - Searching for IgA nephropathy candidate genes: genetic studies combined with high
      throughput innovative investigations.
AB  - Idiopathic IgA Nephropathy (IgAN) is the most common biopsy-proven
      glomerulonephritis worldwide. All races with the exception of Blacks and Indians
      are involved. Families with two or more relatives affected by IgAN may be
      observed in 15-20% of pedigrees of IgAN patients. Genome wide linkage study has
      been considered the most promising approach to identify IgAN susceptibility
      genes. Therefore, some European investigators constituted the European IgAN
      Consortium which was initially funded by the European Union. Data from linkage
      analysis studies, family association studies and case-control association studies
      are reported. To date, the Consortium has identified two loci (located on
      chromosomes 4q26-31 and 17q12-22), in addition to the previous study which
      described the first IgAN locus on chromosome 6q22-23. The functional mapping of
      genes involved in the disease proceeds from the identification of susceptibility
      loci identified by linkage analysis (step 1) to the isolation of candidate genes
      within gene disease-susceptibility loci, after obtaining information by
      microarray analysis carried out on peripheral leukocytes and renal tissue samples
      (step 2). Then, the process will proceed from the design of RNA
      interferenceagents against selected genes (step 3) to the application of
      systematically tested effect of RNA agents on functional cellular assay (step 4).
      The above combined high-throughput technologies will give information on the
      pathogenic mechanisms of IgAN. In addition, these data may indicate potential
      targets for screening, prevention and early diagnosis of the disease and more
      appropriate and effective treatment.

PMID- 17495442
TI  - Clinicopathological influence of obesity in IgA nephropathy: comparative study of
      74 patients.
AB  - The pathological role of obesity has rarely been studied in primary glomerular
      diseases. The purpose of this study is to examine the clinicopathological
      influence of obesity in IgA nephropathy (IgAN). 74 patients with IgA nephropathy
      in our institution from October 2000 to January 2004 were retrospectively divided
      into two groups according to body mass index (BMI): the non-obese group (group N)
      with BMI < 25 kg/m(2), and the obese group (group O) with BMI > or = 25 kg/m(2).
      There were 50 patients in group N and 24 patients in group O. Clinical analysis
      showed no significant difference between these two groups in blood pressure,
      serum cholesterol, creatinine clearances or grade of hematuria. However, urinary
      protein excretion and serum creatinine were significantly greater in group O than
      in group N. Although semiquantitative analysis of light-microscopical findings
      showed no significant differences in the severity of mesangial proliferation,
      matrix expansion, glomerulosclerosis or crescent formation, image analysis showed
      that total glomerular area and tuft area were significantly larger in group O. In
      addition, ultrastructural study revealed significantly higher glomerular basement
      membrane thickness in group O. 62 patients (46 patients, group N; 16 patients,
      group O) were followed in our institution for one year. Urinary protein was
      significantly decreased only in patients who received steroid in both groups.
      Although administration of ACE inhibitor or ARB tended to decrease urinary
      protein in group O, the change was not statistically significant. Our findings
      indicate that obesity may accelerate the increase of proteinuria in IgAN through
      ultrastructural modification of the glomerular basement membrane.

PMID- 17495443
TI  - A multicenter prospective cohort study of tonsillectomy and steroid therapy in
      Japanese patients with IgA nephropathy: a 5-year report.
AB  - Tonsillectomy combined with corticosteroids has been performed for IgA
      nephropathy (IgAN) mainly in Japan. We, the Japanese Multicenter Study Group on
      the Treatment of IgA Nephropathy (JST-IgAN), have conducted a multicenter
      prospective cohort study including the combination therapy from 1999. A total of
      101 patients (43 male, 58 female) were observed for 5 years. Their average age
      was 34.4 +/- 11.8 (15-55). Subjects were classified by daily proteinuria (UP) and
      serum creatinine (sCr); UP excreted below 0.5 g/day was defined as stage 1, 0.5
      1.0 g/da y defined as stage 2, more than 1.0 g/da y and sCr < or =1.2 mg/dl in
      females or < or =1.4 mg/dl in males defined as stage 3, and sCr >1.2 mg/dl in
      females or >1.4 mg/dl in male defined as stage 4. Both tonsillectomy and high
      dose corticosteroid were performed in 75 patients. Of these, 29 patients were
      stage 1, 26 were stage 2, 16 were stage 3, and 4 were stage 4. The number of
      subjects with steroid monotherapy were 1 (stage 1), 7 (stage 2), 9 (stage 3) and
      1 (stage 4). The primary endpoint in this study was normalized urinalysis as
      clinical remission. The remission rate treated with combined therapy was 86.2% in
      stage 1, 73.1% in stage 2, and 43.8% in stage 3. On the other hand, it was 71.4%
      in stage 2, and 11.1% in stage 3 in steroid monotherapy subjects. Although the
      number in each treatment group varied because of the non-randomized study,
      tonsillectomy combined with 3 courses of high-dose corticosteroid therapy was
      more effective for clinical remission in the higher proteinuria group. We
      concluded that the goal should be cure and release from disease at an earlier
      stage of IgAN.

PMID- 17495444
TI  - Tonsillectomy and corticosteroid therapy with concomitant methylprednisolone
      pulse therapy for IgA nephropathy.
AB  - IgA nephropathy (IgAN) is the most common chronic kidney disease in Japan, but
      the optimum treatment remains controversial. Our objective was to evaluate the
      effect of tonsillectomy and corticosteroid therapy combined with methylprednisone
      pulse therapy in patients at our hospital who had IgAN. Tonsillectomy plus pulse
      therapy was evaluated in 72 patients (33 men and 39 women) with a diagnosis of
      IgAN based on renal biopsy who were followed up for more than 1 year. The mean
      age of the patients was 35.2 +/- 10.9 years (range: 20-58 years) and the mean
      observation period after tonsillectomy was 20.3 +/- 9.7 months (range: 12-36
      months). After tonsillectomy, steroid pulse therapy was administered
      (methylprednisolone at 500 mg daily for 3 days) 1-3 times and was followed by
      oral prednisolone from an initial dose of 30 mg on alternate days that was
      tapered gradually over one year. At 2 years after tonsillectomy, serum creatinine
      was unchanged or improved in the majority of patients, but worsened in 5
      patients. Hematuria (erythrocytes/HPF) improved from Grade 3.76 (11-30/HPF) to
      Grade 1.94 (1-5/HPF) on average (we defined the grade of hematuria). None of the
      patients experienced exacerbation of hematuria. Proteinuria decreased from 1.32
      g/day to 0.86 g/day (65% of the pretreatment value), and only 4 patients showed
      an increase of proteinuria. Mean protein loss decreased to less than 0.5 g/day in
      patients with creatinine clearance > or =90 ml/min and/or patients with initial
      protein excretion < or =1.0 g/day.

PMID- 17495445
TI  - Impact of annual urine health check-up system to obtain clinical remission in
      patients with IgA nephropathy.
AB  - PURPOSE: In Japan, the annual urine health check-up system is well developed.
      Recently we reported a significant impact of tonsillectomy and steroid pulse
      therapy on clinical remission in our IgA nephropathy (IgAN) patients and
      indicated that clinical remission might terminate the progressive deterioration
      in renal function. We surveyed whether early detection of urinary abnormalities
      by annual urine health check-ups contribute to clinical remission in IgAN
      patients treated with tonsillectomy and steroid pulse therapy. METHODS: We
      investigated 380 IgAN patients in whom the onset year was identified by annual
      urine check-ups. Group A consisted of 264 patients in whom treatment intervention
      was initiated within 3 years after the first appearance of urinary abnormalities,
      and group B consisted of 116 patients who were diagnosed after more than 3 years
      duration of urinary abnormalities. We also classified our 380 patients by the
      degree of glomerular lesions; 233 patients with mild, 83 with moderate, and 64
      with severe glomerular lesions. All patients were treated with tonsillectomy and
      steroid pulse therapy in our renal unit. RESULTS: The clinical remission rate of
      group A was 87.1%, while that of group B was 54.3%. In the mild glomerular lesion
      group, group B had a significantly lower remission rate than group A. Even in the
      severe glomerular lesion group, the remission rate of group A was significantly
      higher than that of group B. CONCLUSION: Our results indicate the annual health
      check-up system to be very useful for achieving clinical remission in IgAN
      patients, if they are treated with tonsillectomy and steroid pulse therapy.

PMID- 17495446
TI  - Sequential immunosuppressive therapy in progressive IgA nephropathy.
AB  - BACKGROUND: Cyclophosphamide and high-dose steroids have been used as limited
      induction therapy in progressive IgA nephropathy (IgAN) to reduce the loss of
      renal function and proteinuria. We evaluated the effect of cyclophosphamide
      pulses (CyP) and mycophenolic acid (MPA) as sequential therapy on renal function
      in patients with progressive IgAN. METHODS: Twenty patients with progressive IgAN
      and advanced renal failure (median GFR 22 ml/min per 1.73 m2) and further disease
      activity (triangle downGFR -0.8 ml/min per month) after cyclophosphamide (CyP; n
      = 18) or steroid pulse therapy (n = 2) were treated with mycophenolate mofetil 1
      g per day for a median of 27 months. RESULTS: The monthly loss of renal function
      was significantly reduced in linear regression analysis from -2.4 ml/min before
      CyP to -0.12 ml/min with CyP/MPA (p = 0.0009). Estimated renal survival time was
      significantly prolonged by a median of 65 months (p = 0.0014). Proteinuria
      decreased significantly from 1.7 to 0.4 g/l during MPA treatment (p = 0.015). In
      Cox regression analysis, only proteinuria >1.0 g/l was an independent risk factor
      for doubling of creatinine during CyP/MPA treatment (p = 0.03). CONCLUSION: A
      sequential therapy with CyP/MPA may arrest or slow down the loss of renal
      function and reduces proteinuria even in patients who passed the so called 'point
      of no return' with progressive IgAN.

PMID- 17495447
TI  - Prospective trial of combined therapy with heparin/warfarin and renin-angiotensin
      system inhibitors in progressive IgA nephropathy.
AB  - We previously reported that a combined therapy with heparin/warfarin and renin
      angiotensin system (RAS) inhibitors dramatically reduces proteinuria for
      prolonged periods in advanced IgA nephropathy (IgAN). In the present study, we
      prospectively analyzed whether the combined therapy can inhibit the progressive
      decline in renal function of patients with progressive IgAN. Patients who had a
      marked linearity of decline in loss of glomerular filtration rate (GFR), assessed
      by reciprocal serum creatinine plots vs. time for more than one year, were
      recruited in this study if they were histologically diagnosed as IgAN at this
      point of declining renal function. Twelve patients were eligible for trial entry;
      reciprocal serum creatinine plot suggested end-stage renal failure within 5
      years. All patients were treated with continuous intravenous infusion of heparin
      for 8 weeks, followed by oral administration of warfarin, ACE inhibitors and/or
      angiotensin II receptor blockers and dypiridamole. Eight patients were further
      given corticosteroid for 2 years because of the presence of acute glomerular
      lesions such as cellular crescent or angionecrosis. All patients were followed-up
      for at least 12 months, and the mean follow-up period was 34 +/- 20 (range 12-79)
      months. After the combined therapy, urinary protein excretion was significantly
      reduced from 2.4 +/- 1.5 g/day at baseline to 0.7 +/- 0.5 g/day at final
      observation, while the mean serum creatinine was not significantly different. Of
      note, the mean slope of 1/serum creatinine significantly increased from -0.009 to
      +0.0002 dl/mg/week (p < 0.05). Moreover, histological analysis of a repeat kidney
      biopsy which was performed in 5 patients at 2 years after the institution of the
      combined therapy revealed that the percentage of cellular/fibrocellular crescent
      and the degree of mesangial matrix expansion were significantly attenuated (19-
      >0.1% and 1.6-->0.6 score, respectively) while the percentage of global sclerosis
      and tubulointerstitial lesion did not increase. These results indicate that our
      combined therapy with heparin/warfarin and RAS inhibitors can inhibit the
      progressive decline in renal function Combined Heparin/Warfarin and RAS
      Inhibitors in Progressive IgAN 115 of patients with progressive IgAN through its
      marked antiproteinuric and anti-inflammatory effects.

PMID- 17495448
TI  - Downregulation of the beta1,3- galactosyltransferase gene in tonsillar B
      lymphocytes and aberrant lectin bindings to tonsillar IgA as a pathogenesis of
      IgA nephropathy.
AB  - IgA is a glycoprotein with multiple O-glycans. Under-O-glycosylation of the hinge
      in IgA in patients with IgA nephropathy (IgAN) is reported. The development of
      IgAN is frequently preceded by episodes of upper respiratory tract infections
      such as tonsillitis. Therefore, the tonsils may be related to the pathogenesis of
      IgAN. However, the mechanism of underglycosylation in tonsillar IgA has not yet
      been fully elucidated. Since O-glycans in IgA are produced by
      glycosyltransferases, we hypothesized that dysregulation of the enzymes is
      associated with underglycosylation.

PMID- 17495449
TI  - Development of IgA nephropathy-like disease with high serum IgA levels and
      increased proportion of polymeric IgA in Beta-1,4-galactosyltransferase-deficient
      mice.
AB  - The glycosylation of glycoproteins is important for their biological activity,
      conformation and stability. Recent studies indicate that aberrant glycosylation
      causes various human disorders. Here we report that mice lacking beta-1,4
      galactosyltransferase-I (beta4GalT-I), which transfers galactose from UDP-Gal to
      terminal GlcNAc of N- and O-glycans in a beta-1,4- linkage, developed IgA
      nephropathy (IgAN)-like disease. Urinary albumin levels were significantly
      increased in the beta4GalT-I-deficient mice. Hematuria was detected in some of
      the beta4GalT-I-deficient mice, suggesting impaired renal function. Furthermore,
      histological and immunohistochemical examination showed expanded mesangial
      matrix, IgA deposition with mesangial pattern and electron-dense deposits in the
      paramesangial regions in the beta4GalT-Ideficient mice. These results demonstrate
      that the beta4GalT-I-deficient mice developed IgANlike disease. Furthermore, high
      serum IgA levels with increased polymeric forms were detected. In humans, serum
      IgA derived from patients with IgAN has aberrant beta3-galactosylation and
      sialylation on its O-linked glycans of the hinge region. Mouse IgA does not have
      O-glycans of the hinge region and has several N-glycans. As expected, beta4
      galactosylation on the N-glycans of the serum IgA of the beta4GalT-I-deficient
      mice was completely absent. This is the first report demonstrating that genetic
      remodeling of protein glycosylation causes IgAN. We suggest that aberrant beta4
      galactosylation of serum IgA participates in the
      Nishie/Miyaishi/Azuma/Kameyama/Naruse/Hashimoto/Yokoyama/Narimatsu/Wada/Asano 126
      development of IgAN, including deposition of IgA, polymerization of IgA, and
      glomerular injury after IgA deposition.

PMID- 17495450
TI  - IgA nephropathy: characterization of IgG antibodies specific for galactose
      deficient IgA1.
AB  - The circulating immune complexes in IgA nephropathy (IgAN) are composed of
      galactose (Gal)-deficient IgA1 bound to IgG or IgA1 antibodies specific for hinge
      region O-linked glycans of Gal-deficient IgA1. To analyze properties of the anti
      glycan antibodies, we determined the binding of serum IgG and IgG secreted by
      Epstein-Barr virus (EBV)- immortalized B cells from patients with biopsy-proven
      IgAN (n = 12) and healthy controls (n = 5) to a panel of antigens coated on ELISA
      plates. These antigens were: (1) enzymatically desialylated and degalactosylated
      IgA1 myeloma protein (dd-IgA1), (2) Fab fragment of Gal-deficient IgA1 containing
      part of the hinge region with O-glycans (Fab-IgA1), (3) synthetic hinge-region
      peptide linked to bovine albumin (HR-BSA), and (4) synthetic hingeregion
      glycopeptide with three GalNAc residues linked to BSA (HR-GalNAc-BSA). IgG
      secreting EBV-immortalized cell lines were subcloned by limiting dilution. The
      concentration of total IgG and distribution of IgG subclasses were measured by
      ELISA. The levels of IgG in sera and supernatants directed against dd-IgA1 and
      Fab-IgA1 were significantly higher in IgAN patients than in controls (p < 0.01).
      IgG from IgAN patients exhibited strong reactivity with HR-GalNAc-BSA, but not
      with HR-BSA. The IgG-secreting cell lines produced antibodies specific to dd
      IgA1; the antigen-specific IgG was most frequently of the IgG2 subclass. In
      summary, sera and supernatants from IgG-secreting cell lines from patients with
      IgAN were characterized by high levels of IgG antibodies with specificity to the
      Gal-deficient O-linked glycans of IgA1. The immortalized cell lines will provide
      a stable and convenient source of IgG for molecular studies of antibodies
      specific to the aberrant O-glycans in IgA1.

PMID- 17495451
TI  - IgA nephropathy and Henoch-Schoenlein purpura nephritis: aberrant glycosylation
      of IgA1, formation of IgA1-containing immune complexes, and activation of
      mesangial cells.
AB  - IgA1 in the circulation and glomerular deposits of patients with IgA nephropathy
      (IgAN) is aberrantly glycosylated; the hinge-region O-linked glycans are
      galactose-deficient. The circulating IgA1 of patients with Henoch-Schoenlein
      purpura nephritis (HSPN) has a similar defect. This aberrancy exposes N
      acetylgalactosamine-containing neoepitopes recognized by naturally occurring IgG
      or IgA1 antibodies resulting in formation of immune complexes. IgA1 contains up
      to six O-glycosylation sites per heavy chain; it is not known whether the
      glycosylation defect occurs randomly or preferentially at specific sites. We
      sought to define the aberrant glycosylation of a galactose-deficient IgA1 myeloma
      protein and analyze the formation of the immune complexes and their biological
      activities. Supplementation of serum or cord-blood serum with this IgA1 protein
      resulted in formation of new IgA1 complexes. These complexes stimulated
      proliferation of cultured human mesangial cells, as did the naturally-occurring
      IgA1-containing complexes from sera of patients with IgAN and HSPN. Uncomplexed
      IgA1 did not affect cellular proliferation. Using specific proteases, lectin
      Western blots, and mass spectrometry, we determined the O-glycosylation sites in
      the hinge region of the IgA1 myeloma protein and IgA1 proteins from sera of IgAN
      patients. The IgA1 myeloma protein had galactose-deficient sites at residues 228
      and/or 230 and 232. These sites reacted with IgG specific to galactose-deficient
      IgA1. IgA1 from the IgAN patients had galactose-deficient O-glycans at the same
      residues. In summary, we identified the neoepitopes on IgA1 responsible for
      formation of the pathogenic immune complexes. These studies may lead to
      development of noninvasive diagnostic assays and future disease-specific therapy.

PMID- 17495452
TI  - Patients with IgA nephropathy respond strongly through production of IgA with low
      avidity against Staphylococcus aureus.
AB  - BACKGROUND: Post-methicillin-resistant Staphylococcus aureus infection
      glomerulonephritis (post-MRSA infection GN) is seen after MRSA infection and is a
      similar disorder to IgA nephropathy (IgAN). We have found that immune complexes
      composed of staphylococcal cell membrane antigen and IgA are deposited in the
      glomerular mesangial areas in patients with post-MRSA infection GN and in more
      than 60% of patients with IgAN. AIM: To examine the characteristics of serum IgA
      obtained from patients with IgAN. PATIENTS AND METHODS: Experiment 1. Serum
      samples were obtained from patients with IgAN (n = 16) and post-MRSA infection GN
      (n = 19), and from healthy donors (n = 13). Serum IgA and IgG titers against
      Staphylococcus aureus (S. aureus) were measured using an ELISA. Experiment 2.
      Relative antibody avidities of serum IgA and IgG against S. aureus from patients
      and healthy donors were determined in a dissociation assay using an ELISA.
      RESULTS: Experiment 1. IgA class titers of anti-S. aureus antibodies in patients
      with IgAN and post-MRSA infection GN were significantly higher than in healthy
      controls, and IgG class titers of anti-S. aureus antibodies in patients with post
      MRSA infection GN were significantly higher than those in IgAN patients and
      healthy donors. A significant correlation between IgG and IgA titers was found
      across all cases, and this was particularly evident in patients with IgAN.
      Experiment 2. No significant correlation was observed between avidity and titer
      of IgA class antibodies. The avidity of anti-S. aureus IgG did not differ
      significantly between IgAN patients, post-MRSA infection GN patients, and healthy
      donors, but the avidity of anti-S. aureus IgA from patients with IgAN was
      significantly lower than that from the other groups. There was a significant
      correlation between antibody titer and antibody avidity for the IgG class in
      patients with post-MRSA GN, but no significant correlation was observed for the
      IgA class. CONCLUSION: These results suggest that patients with IgAN have a
      strong response through production of IgA with low avidity against S. aureus.

PMID- 17495453
TI  - Transferrin receptor engagement by polymeric IgA1 induces receptor expression and
      mesangial cell proliferation: role in IgA nephropathy.
AB  - IgA nephropathy (IgAN) is characterized by IgA immune complex-mediated mesangial
      cell proliferation. We have previously identified the transferrin receptor (TfR)
      as an IgA1 receptor and found that, in kidney biopsies of patients with IgAN, TfR
      is overexpressed and co-localized with IgA1 mesangial deposits. We also showed
      that IgA1 binding to TfR was strikingly increased when IgA1 was
      hypogalactosylated and of high molecular weight, both features found in IgA from
      IgAN patients. More recently, we showed that purified polymeric IgA1 (pIgA1) is a
      major inducer of TfR expression (3-fold increase) in quiescent human mesangial
      cells (HMC). In addition, sera from IgAN patients upregulate TfR expression in
      cultured HMC in an IgA-dependent manner. IgA1-induced HMC proliferation is
      dependent on TfR engagement and can be inhibited by both TfR1 and TfR2
      ectodomains as well as by the anti-TfR mAb A24. Finally, activation of mesangial
      cells through pIgA1 binding to TfR induced secretion of IL-6 and TGF-beta from
      the cells, that could be involved, respectively, in the inflammatory and pro
      fibrogenic events observed in IgAN. We propose that deposited pIgA1 or IgA immune
      complexes could initiate an auto-amplification process involving hyper-expression
      of TfR allowing increased IgA1 mesangial deposition. Altogether, these data
      unveil a functional cooperation between pIgA1 and TfR for IgA1 deposition and HMC
      proliferation, features which are commonly implicated in the chronic mesangial
      injuries observed in IgAN.

PMID- 17495454
TI  - IgA Fc receptor I is a molecular switch that determines IgA activating or
      inhibitory functions.
AB  - IgA Fc receptor I, FcalphaRI or CD89, an ITAM-bearing receptor, has revealed
      unique genetic, structure and function features among immunoreceptors. While all
      genes encoding for the human Fc receptors are located in chromosome 1, the
      FcalphaRI gene has been found in a cluster in 19q13 that includes the killer
      inhibitory receptors (KIRs) and the leukocyteimmunoglobulin- like receptors
      (LIRs). FcalphaRI-IgA complexes display an original crystal structure and a 2:1
      stoichiometry. Our results show that intrinsic signals elicited by FcalphaRI have
      outlined the particularity of this receptor, since it could function in two
      opposite ways: cell activation and inhibition of a heterologous FcR. Contrary to
      the dogma that receptor multimerization is necessary to ensure signaling, we
      demonstrated that monomeric targeting of FcalphaRI is sufficient to trigger a low
      intensity signaling cascade that leads to cell desensitization by recruiting the
      tyrosine phosphatase SHP-1. By contrast, multimerization of FcalphaRI allows a
      high-intensity signaling pathway that leads to the recruitment of tyrosine kinase
      Syk and cell activation. Both types of signals require the FcRgamma-ITAM motif.
      This dual function is unique among ITAM-bearing FcR and led us to postulate that
      ITAM motifs could deliver an unexpected array of signaling intensity. These
      findings redefine FcalphaRI as a molecular switch of the immune system that
      mediates both pro- and anti-inflammatory functions of IgA.

PMID- 17495455
TI  - The role of PDGF-D in mesangioproliferative glomerulonephritis.
AB  - In view of increasing numbers of patients with end-stage renal disease (ESRD),
      new approaches to common underlying diseases, such as mesangioproliferative
      glomerulonephritis, including IgA nephropathy, are urgently needed. Whereas the
      role of the platelet-derived growth factor (PDGF) B chain in mediating
      mesangioproliferative changes is well established, the role of the PDGF-D chain
      has only recently been elucidated. The PDGF-D chain, like PDGF-B, signals through
      the PDGF beta-receptor and therefore shares a number of biological activities
      with PDGF-B. Recent studies have shown that PDGF-D induces mesangial cell
      proliferation in vitro and is overexpressed in mesangioproliferative
      glomerulonephritis in vivo. Hepatic transfection with an adenoviral vector
      expressing PDGF-D induced prominent mesangioproliferative nephritis in mice,
      whereas antagonism of PDGF-D in a rat model of mesangioproliferative disease
      ameliorated the renal changes. These four observations establish PDGF-D, like -B,
      as an important mediator of mesangioproliferative nephritis in vivo and suggest
      that it may be an attractive therapeutic target. In addition, first observations
      suggest that PDGF-D may also contribute to secondary renal changes that
      characterize progressive renal failure, i.e. tubulointerstitial fibrosis.

PMID- 17495456
TI  - Analysis of innate immune responses in a model of IgA nephropathy induced by
      Sendai virus.
AB  - In a model of IgA nephropathy (IgAN) induced by Sendai virus (SeV) without
      Th1/Th2 polarizing immunization, Th2-prone BALB/c mice develop more severe
      nephritis with acute renal insufficiency than Th1-prone C3H mice. To determine
      whether Th1 or Th2 predominance influences the severity of experimental IgAN in
      mice, we employed polarizing immunizations in a SeV-induced IgAN model in Th1
      prone C57Bl/6 mice and Th2-prone BALB/c mice. C57Bl/6 mice, immunized with SeV
      +CFA or +IFA, showed: (1) clear cytokine polarity by splenocytes in recall
      assays. (2) Total serum IgA and especially SeV-specific IgA from the IFA group
      showed a selective defect in galactosylation, not seen in the CFA group, and (3)
      serum creatinine in the IFA group was higher than in the CFA group or nonimmune
      controls. However, BALB/c mice did not show clear cytokine polarity with CFA/IFA
      adjuvant. Moreover, spleen cells from naive BALB/c mice produce IFN-gamma (but
      not IL-2, -4, -5, or -13) upon stimulation with inactivated SeV in vitro. By flow
      cytometry, IFN-gamma producing cells are CD3(-), CD19(-), CD49b(+) natural killer
      cells. IFN-gamma production by naive splenocytes is blocked partially by anti
      IL12 blocking Abs, and completely by anti-IL18R blocking Abs. In conclusion,
      C57Bl/6 mice with polarizing priming with SeV showed clear cytokine polarity and
      distinct kidney injuries. However, BALB/c mice did not show clear cytokine
      polarity in the same immunizing system, presumably due to the effects of innate
      responses to SeV upon antigen-specific lymphocytes. Natural IFN-gamma production
      may influence the risk of renal failure in IgAN.

PMID- 17495457
TI  - Roles of bone marrow, mucosa and lymphoid tissues in pathogenesis of murine IgA
      nephropathy.
AB  - Previous studies indicated that bone marrow cells may contribute to the
      pathogenesis of IgA nephropathy (IgAN). However, the cell types and mechanisms
      responsible remain unclear. Our recent study showed that 'grouped ddY mice' is a
      useful model to approach the pathogenesis of IgAN. Moreover, we also reported
      that bone marrow transplantation (BMT) from the onset mice of this model
      reconstituted IgAN in healthy recipients with strong Th1-polarization. We aimed
      to examine the roles of bone marrow (BM) cells, mucosa and lymphoid tissues in
      IgAN. We employed onset ddY mice and mutant mice lacking all systemic lymph
      nodes, Payer's patch, isolated lymphoid follicles in the lamina propria (LP) and
      IgA producing cells. BM cells from the onset mice were transplanted into the
      mutant and wild type (C57BL/6:B6). After BMT, serum elevation of IgA and
      IgA(+)B220(-) plasma cells in BM, but not IgA producing cells in LP, were
      observed in the mutant mice. Although both transplanted mice showed mesangial IgA
      deposition, glomerular lesions with IgG2a co-deposition were detected only in B6
      mice. The present results suggest that glomerular IgA deposition, but not
      glomerular damage, can be induced by BM-derived or -primed IgA-producing cells
      independently of priming in mucosa and secondary lymphoid tissues.

PMID- 17495458
TI  - Concluding remarks.

PMID- 17495462
TI  - Effect of cardioactive drugs on action potential generation and propagation in
      embryonic stem cell-derived cardiomyocytes.
AB  - Extracellular recordings of spontaneous electrical activity in contracting
      cardiac clusters differentiated from murine embryonic stem cells enable to study
      electrophysiological features of this in-vitro cardiac-like tissue as well as
      effects of pharmacological compounds on its chronotropy and electrical
      conduction. To test if the microelectrode array (MEA) system could serve as a
      basis for development of a pharmacological screening tool for cardioactive drugs,
      we used spontaneously beating outgrowths of three-dimensional ES cell aggregates
      ("embryoid bodies", EBs) plated onto substrate-integrated MEAs. The effects of
      the L-type Ca(2+) channel antagonist verapamil and Na(+) and K(+) channel
      blockers (tetrodotoxin, 4-aminopyridine, and sparfloxacin) on the deduced
      interrelated cardiac network function were investigated. Application of 10(-6) M
      verapamil led to arrhythmic spiking with a burst-like pattern; at a higher
      concentration (10(-5) M) the drug caused a sustained negative chronotropy up to
      complete stop of beating. In the presence of tetrodotoxin a conduction block was
      observed. Since modulation of K(+) channel activity can cause anti- or
      proarrhythmic effects, the influence of K(+) channel blockers, namely 4
      aminopyridine and sparfloxacin, was investigated. 4-aminopyridine (2x10(-3) M)
      significantly stabilized beating frequency, while the field potential duration
      (FPD) was concentration-dependently prolonged up to 2.7-fold. Sparfloxacin (3x10(
      6) M) stabilized the beating frequency as well. At a higher concentration of
      sparfloxacin (3x10(-5) M), a significant prolongation of the spike duration was
      registered; application of the drug caused also early afterdepolarizations. The
      results demonstrate a suitability of the studied in-vitro cardiac cell model for
      pharmacological drug testing in cardiovascular research.

PMID- 17495463
TI  - Ionic mechanisms underlying abnormal QT prolongation and the associated
      arrhythmias in diabetic rabbits: a role of rapid delayed rectifier K+ current.
AB  - Abnormal QT prolongation with the associated arrhythmias is considered the major
      cardiac electrical disorder and a significant predictor of mortality in diabetic
      patients. The precise ionic mechanisms for diabetic QT prolongation remained
      unclear. We performed whole-cell patch-clamp studies in a rabbit model of alloxan
      induced insulin-dependent diabetes mellitus. We demonstrated that heart rate
      corrected QT interval and action potential duration (APD) were prolonged by
      approximately 20% with frequent occurrence of ventricular tachyarrhythmias.
      Several K(+) currents were found decreased in diabetic rabbits including
      transient outward K(+)current (I(to)) that was reduced by approximately 60%,
      rapid delayed rectifier K(+) current (I(Kr)) reduced by approximately 70% and
      slow delayed rectifier K(+) current (I(Ks)) reduced by approximately 40%. The
      time-dependent kinetics of these currents remained unaltered. The peak amplitude
      of L-type Ca% current (I(CaL)) was reduced by approximately 22% and the
      inactivation kinetics was slowed; the integration of these two effects yielded
      approximately 15% reduction of I(CaL). The inward rectifier K(+) current (I(K1))
      and fast sodium current (I(Na)) were unaffected. Simulation with LabHEART, a
      computer model of rabbit ventricular action potentials, revealed that inhibition
      of I(to) or I(Ks) alone fails to alter APD whereas inhibition of I(Kr) alone
      results in 30% APD prolongation and inhibition of I(CaL) alone causes 10% APD
      shortening. Integration of changes of all these currents leads to approximately
      20% APD lengthening. Protein levels of the pore-forming subunits for these ion
      channels were decreased to varying extents, as revealed by immunoblotting
      analysis. Our study represents the first documentation of I(Kr) channelopathy as
      the major ionic mechanism for diabetic QT prolongation.

PMID- 17495464
TI  - Functional characterization of a novel CFTR mutation P67S identified in a patient
      with atypical cystic fibrosis.
AB  - Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene. CFTR serves as a cAMP-stimulated chloride
      channel in a wide range of epithelial tissues and its dysfunction is a hallmark
      of CF. Over 1400 mutations in the CFTR gene are known, but functional data exist
      only for a minority of the mutant channels. The aim of the present study was to
      functionally characterize a novel CFTR mutation identified in a patient with
      atypical CF. Full length sequencing of the patient's CFTR gene revealed a
      homozygous C to T transition at nucleotide position 331 (CCT>TCT), which results
      in a P67S amino acid substitution. Mutant and wild-type CFTR were heterologously
      expressed in Xenopus laevis oocytes. CFTR whole-cell currents were studied using
      the two-electrode voltage-clamp technique. Channel surface expression was
      assessed by a chemiluminescence assay. Expression of P67S-CFTR resulted in
      functional CFTR chloride channels. However, the CFTR chloride conductance
      observed in oocytes expressing the mutant channel averaged only 24% of that in
      oocytes expressing wild-type CFTR. Similarly, surface expression of the mutant
      channel was reduced. In contrast, the mutation did not alter the anion
      selectivity of the channel, and Western blot analysis indicated a similar protein
      expression level of mutant and wild-type CFTR. Our findings indicate that the
      P67S mutation reduces CFTR chloride channel function by reducing channel surface
      expression. The mild disease phenotype of the patient indicates that the residual
      function of the mutant channel is sufficient to prevent the development of severe
      CF symptoms.

PMID- 17495465
TI  - Blockage of volume-activated chloride channels inhibits migration of
      nasopharyngeal carcinoma cells.
AB  - Cell migration is crucial for tumor metastasis. Membrane ion channels may play a
      major role in tumor cell migration because the cells must undergo changes in
      shape and volume during migration. In the present study, we used the transwell
      migration assay, an in vitro model for cell migration, and the patch-clamp
      technique to investigate the role of the volume-activated Cl(-) current
      (I(cl,vol)) in the regulation of the migration of nasopharyngeal carcinoma CNE-2Z
      cells. 5-Nitro-2- (3-phenylpropylamino) benzoic acid (NPPB) inhibited the
      I(cl,vol) and the migration of CNE-2Z cells with almost identical dose-dependent
      pattern (IC(50) of 98.1 microM and 97.7 microM for I(cl,vol) and cell migration,
      respectively). Extracellular adenosine triphosphate (ATP) also showed similar
      dose-dependent inhibitory effects on the currents and migration (IC(50) of
      1.07mM, and 1.11mM for I(cl,vol) and cell migration, respectively). Hypotonic
      treatments, which activated I(cl,vol), increased cell migration. Exposure to
      hypertonic solutions, which was shown to suppress I(cl,vol), inhibited cell
      migration. Replacement of Cl(-) with gluconate, which is relatively chloride
      channel-impermeable, impaired cell migration, whereas substitution of Cl(-) by I(
      ) and Br(-), the chloride channel-permeable ions, did not significantly affect
      cell migration. Analysis of the effects of all the above treatments on I(cl,vol)
      and cell migration indicated that the inhibition of migration was positively
      correlated with the blockage of I(cl,vol), with a correlation coefficient (r) of
      0.97, suggesting a functional relationship between I(cl,vol) and cell migration.
      These data suggest that the volume-activated Cl(-) channels are involved in cell
      migration.

PMID- 17495466
TI  - Differential regulation of cell volume and shape in confluent rat hepatocytes
      under hypertonic stress.
AB  - In confluent primary cultures of rat hepatocytes,hypertonic stress leads to cell
      shrinkage and activates non-selective cation channels as the main mechanism of
      regulatory cell volume increase. The process is found to employ the exocytotic
      insertion of channels into the plasma membrane and (in addition to PKC) PLC,
      tyrosine kinases and G proteins, but not PI 3-kinase are part of the signalling
      network. Furthermore, hypertonic stress leads to the formation of stress fibres
      and significantly alters the activity of RhoA, Rac and Cdc42. These latter
      effects, however, are likely to reflect the restoration of cell shape rather than
      the regulation of cell volume, both most probably converging at the level of
      focal adhesions and integrins.

PMID- 17495467
TI  - Effect of hypoxia on 2-deoxyglucose uptake and cell cycle regulatory protein
      expression of mouse embryonic stem cells: involvement of Ca2+ /PKC, MAPKs and HIF
      1alpha.
AB  - This study investigated the signal molecules linking the alteration in 2
      dexoyglucose (2-DG) uptake and DNA synthesis in mouse embryonic stem (ES) cells
      under hypoxia. Hypoxia increased the 2-DG uptake and GLUT-1 protein expression
      level while the undifferentiated state of ES cells and cell viability were not
      affected by the hypoxia (1 - 48h). Subsequently, [(3)H] thymidine incorporation
      was significantly increased at 12 hours of hypoxic exposure. Hypoxia increased
      the Ca(2+) uptake and PKC beta (I), epsilon, and zeta translocation from the
      cytosol to the membrane fraction. Moreover, hypoxia increased the level of p44/42
      mitogen-activated protein kinases (MAPKs) phosphorylation and hypoxia inducible
      factor-1alpha (HIF-1alpha) in a time-dependent manner. On the other hand,
      inhibition of these pathways blocked the hypoxia-induced increase in the 2-DG
      uptake and GLUT-1 protein expression level. Under hypoxia, cell cycle regulatory
      protein expression [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK
      4] were increased in a time-dependent manner, which were blocked by PD 98059. pRB
      protein was also increased in a time-dependent manner. In conclusion, under
      hypoxia, there might be a parallel relationship between the expression of GLUT1
      and DNA synthesis, which is mediated by the Ca(2+) /PKC, MAPK, and the HIF-1alpha
      signal pathways in mouse ES cells.

PMID- 17495468
TI  - Lactone ring of pectenotoxins: a key factor for their activity on cytoskeletal
      dynamics.
AB  - BACKGROUND: Pectenotoxins are a group of natural products from marine origin that
      can accumulate in shellfish and intoxicate humans. Recently, novel homologues
      such as pectenotoxin-11 (PTX-11) and pectenotoxin-2 seco acid (PTX-2SA) have been
      identified. Their toxic potential towards experimental animals has been evaluated
      however their interaction with cellular systems is almost unknown. This is the
      first report showing (i) the biological activity of PTX-11 and PTX-2SA on actin
      cytoskeleton and morphology of living cells and (ii) the structure- activity
      relationship for this family of toxic compounds. METHODS: Fluorescent phalloidin
      was utilized to quantify and visualize any modification in polymerized actin.
      Fluorescence values were obtained with laser-scanning cytometer and cells were
      imaged through confocal microscopy. For structure-activity evaluations,
      pectenotoxin-1 (PTX-1) and pectenotoxin-2 (PTX-2) was also analyzed. RESULTS:
      Data showed that PTX-11 triggered a remarkable depolymerizing effect on actin
      cytoskeleton and also modifications in the shape of cells. In contrast, PTX-2SA
      did not evidence the same effects. CONCLUSION: Our findings point out that (i)
      the actin cytoskeleton is a common target for PTX-11, PTX-2 and PTX-1, but not
      for PTX-2SA, and (ii) this difference in activity is related to the presence or
      absence of an intact lactone ring in their structures.

PMID- 17495469
TI  - Role of cyclic ADP-ribose-Ca2+ signaling in mediating renin production and
      release in As4.1 cells.
AB  - The present study was designed to test the hypothesis that cyclic-ADP-ribose
      (cADPR) serves as a novel second messenger to mediate intracellular Ca(2+)
      concentration in As4.1 cells, a prototype of renal juxtaglomerular cells, and
      thereby regulates the renin production and release. Western blot analysis showed
      that CD38, an enzyme responsible for the production of cADPR, was abundant in
      As4.1 cells. Using cADPR cycling assay, it was found that NaCl stimulated cADPR
      production in these cells, which was blocked by inhibition of ADP-ribosyl cyclase
      with nicotinamide. HPLC analysis showed that the conversion rate of beta-NGD into
      cGDPR was dramatically increased by NaCl, which was attenuated by nicotinamide.
      Using fluorescent microscopic imaging analysis, NaCl (100 mM) was demonstrated to
      stimulate a rapid Ca(2+) increase from the endoplasmic reticulum (ER), which was
      inhibited by a cADPR antagonist, 8-bromo-cADPR (30 microM), an inhibitor of ADP
      ribosyl cyclase, nicotinamide (6 mM), the ryanodine receptors blocker, ryanodine
      (30 microM), or a Ca(2+)-induced Ca(2+) release inhibitor, tetracaine (10 microM)
      by 70-90%. Finally, NaCl was found to significantly lower the renin production
      and release levels in As4.1 cells, which was accompanied by decreases in renin
      mRNA levels. Pretreatment of these cells with various inhibitors or blockers
      above significantly blocked the inhibitory effect of NaCl on renin production and
      release. These results indicate that cADPR-mediated Ca(2+) signaling pathway is
      present in As4.1 cells and that this signaling pathway may play a contributing
      role in the regulation of renin production and release.

PMID- 17495470
TI  - Separate locations of urocortin and its receptors in mouse testis: function in
      male reproduction and the relevant mechanisms.
AB  - Urocortin (UCN), a newly identified corticotrophin-releasing-factor (CRF) related
      peptide, has been demonstrated to play important roles in female reproductive
      system. However, few studies were reported about its effects on male
      reproduction. This study aimed to investigate the expression profile of UCN and
      CRF receptors (CRFR) in mouse testis and functions of UCN in male reproduction.
      Expression of UCN and CRFR mRNA was detected by RT-PCR. Localization of UCN
      peptide was determined by immunohistochemistry and double-immunostaining. We
      found that both UCN mRNA and peptide were obviously expressed in mature
      spermatozoa, whereas CRFR1 and CRFR2 were expressed respectively in spermatocytes
      and spermatogonia. Double-immunostaining results showed that UCN expression
      decreased with acrosome reaction (AR) proceeding. UCN significantly inhibited AR
      initiated by progesterone with chlortetracycline staining and decreased
      spermatozoa motility concentration-dependently. Pre-incubation of spermatozoa
      with astressin, a CRFR antagonist, did not affect these inhibitions. In addition,
      flow cytometry showed that UCN concentration-dependently decreased intracellular
      Ca(2+) [Ca(2+)](i) in spermatozoa. In summary, UCN located in mouse spermatozoa
      and exerted inhibitory effects on male reproductive functions including motility
      and AR. UCN's inhibition on [Ca(2+)](i) via T-type calcium channels might be
      responsible for these effects.

PMID- 17495471
TI  - Procollagen synthesis is increased in hypothyroid rat ovary by a parallel and
      compensatory pathway.
AB  - Collagen biosynthesis is a multistep process that starts with the transcription
      and translation of the individual collagen gene. It is characterized by the
      presence of a large number of co- and posttranslational modifications.
      Hydroxylysine is found only in animal proteins and mostly in collagens.
      Procollagen lysyl hydroxylation is the first step in collagen biosynthetic
      pathway and lysyl hydroxylases (Plod isoforms) are responsible for this enzymatic
      process. Previously we showed the down regulation of Plod isoforms in hypothyroid
      ovary. As hypothyroidism is a stress for normal animals, we wanted to explore
      whether any compensatory pathway exists to balance the reduced lysyl
      hydroxylation of collagen in hypothyroid rat ovary. In this report we have shown
      that procollagen I and III are increased in hypothyroid condition and
      subsequently decreased upon T(3) add-back. Heat Shock Protein-47 is a collagen
      specific molecular chaperone and its existence in ovary has been documented. The
      genes encoding HSP-47, prolyl-4-hydroxylase-alpha and -beta (P4H-alpha and -beta)
      are increased in hypothyroid condition. Down regulation of lysyl hydroxylase in
      hypothyroid condition results less collagen formation. At the same time over
      production of procollagens, HSP-47 and P4H is very significant as they may
      compensate the damage whatsoever caused due to hypothyroidism in ovarian tissue.

PMID- 17495472
TI  - Is antioxidant therapy a viable alternative for mild cognitive impairment?
      Examination of the evidence.
AB  - Therapeutic interventions for the prodromal stages of dementia are currently
      being sought with a view to delaying if not preventing disease onset. Uncertainty
      as to whether cognitive disorder in a given individual will progress towards
      dementia and adverse drug side effects has led to hesitancy on the part of drug
      regulators to instigate preventive pharmacotherapies. In this context,
      antioxidant therapies may provide a low-risk alternative, targeting very early
      biological changes. While a growing body of knowledge demonstrates both the
      importance of oxidative stress in the aetiology of dementia and the efficacy of
      antioxidant treatment in animal and cellular models, studies in humans are
      presently inconclusive. While some antioxidants, notably flavonoid- or vitamin
      rich diets, appear to lower the relative risk for Alzheimer's disease in humans
      in observational studies, these results must be interpreted in the light of the
      biological complexity of the relationship between oxidative stress and
      neurodegeneration, and the methodological and theoretical shortcomings of studies
      conducted to date. A clearer understanding of these factors will assist in the
      interpretation of the results of the intervention studies which are now being
      undertaken; these studies being the only current means of establishing efficacy
      for preventive drug treatment of Alzheimer's disease.

PMID- 17495473
TI  - Cognitive predictors of donepezil therapy response in Alzheimer disease.
AB  - OBJECTIVES: To examine whether the presence of domain-specific cognitive
      impairments would predict a response to donepezil medication in patients with
      mild-to-moderate Alzheimer disease (AD). METHODS: The protocol was an open-label
      study of 30 AD subjects (mean age 74 years; education 11 years; Mini-Mental State
      Exam (MMSE) 23 of 30) beginning a 6-month course of treatment with donepezil.
      Global response to treatment was determined using a combination algorithm based
      on changes over 6 months in the ADAS-cog, MMSE and CIBIC. In addition, a set of
      neuropsychological and experimental cognitive tests designed to test five domains
      of cognition were administered before beginning therapy in order to determine
      which domain of testing would be predictive to response to treatment. The tests
      examined attention, short-term and working memory, learning and memory, visuo
      spatial motor skills, and lexical-semantic knowledge. RESULTS: Eighteen of the
      thirty subjects were rated as having responded (stable or improved scores on the
      combination algorithm) to the therapy. Responders were significantly less
      impaired prior to treatment on the following tests: the Clock Drawing Test, a
      Visual-Spatial Motor Tracking Test, and the Boston Picture Naming Test. No
      significant initial group differences were noted on the other neuropsychological
      or experimental cognitive measures. CONCLUSION: The tests that most reliably
      predicted response to donepezil in AD subjects were in the domains of visual
      spatial motor abilities and lexical-semantic functioning.

PMID- 17495475
TI  - Frequency and clinical characteristics of early-onset dementia in consecutive
      patients in a memory clinic.
AB  - AIMS: To investigate the frequency, rate of causes of dementia, and clinical
      characteristics of early-onset dementia in consecutive patients of a memory
      clinic. METHODS: A total of 668 consecutive demented patients were involved in
      this study. We examined the distribution of patients' diagnosis, differences in
      sex, education, dementia severity and cognitive function at the first visit, and
      the duration from onset to consultation. We also examined the changes in the
      proportion of subjects during the research period. RESULTS: There were 185 early
      onset patients, 28% of all demented patients. No significant differences were
      observed between the early-onset and late-onset dementia groups in Clinical
      Dementia Rating and Mini-Mental State Examination score at the first
      consultation, but the duration from onset to consultation was significantly
      longer in the early-onset group. In the early-onset group, the rates of patients
      with Alzheimer's disease and dementia with Lewy bodies were relatively low and
      the rate of patients with frontotemporal lobar degeneration was relatively high.
      There were no significant differences in the proportion between either demented
      subjects and nondemented subjects or early-onset dementia patients and late-onset
      dementia patients during the research period. CONCLUSION: We conclude that early
      onset dementia is not rare and its clinical characteristics and causes are
      different from late-onset dementia.

PMID- 17495474
TI  - A placebo-controlled double-blind randomized study of venlafaxine in the
      treatment of depression in dementia.
AB  - BACKGROUND/AIMS: To evaluate the efficacy and safety of venlafaxine in the
      treatment of major depression in dementia. METHODS: Thirty-one outpatients who
      had dementia and major depression participated in this randomized, double-blind,
      placebo-controlled, 6-week, flexible dose clinical trial. The screening measures
      were Cornell Scale for depression in dementia, DSM-IV for depression and dementia
      and Mini-Mental State Examination. The outcome measures were response rate,
      Montgomery-Asberg Depression Rating scale and Clinical Global Impressions.
      RESULTS: The percentage of patients defined as Montgomery-Asberg Depression
      Rating scale responders was approximately the same in the placebo and in the
      venlafaxine groups. Clinical Global Impressions showed no significant difference
      between the groups. The reasons for dropouts show borderline significance between
      the two groups. There was no statistically significant difference in the
      incidence of adverse events between the venlafaxine and placebo-treated groups.
      CONCLUSIONS: Our data do not support the hypothesis that venlafaxine improves
      mood in elderly demented patients.

PMID- 17495476
TI  - Prevention of abdominal adhesions--present state and what's beyond the horizon?
AB  - Intra-abdominal adhesions are normally found after most surgical procedures. Many
      of the adhesions are asymptomatic, but in about 5% they will lead to readmission
      due to adhesion-related disorders, such as small bowel obstruction, pelvic pain
      and infertility. This review discusses possible ways to prevent abdominal
      adhesions and provides an update as comes to where we stand today in research
      regarding experimental and clinical use of various antiadhesive agents.

PMID- 17495477
TI  - Effects of varicocele on electrical field stimulation-induced biphasic twitch
      responses in the ipsilateral and contralateral rat vasa deferentia.
AB  - AIM: Although little is known about the mechanisms, varicocele is considered as
      one of the factors leading to male infertility. Since reduced motility of the vas
      deferens was shown to contribute to male infertility, in this study we aimed to
      investigate the effect of varicocele on electrical field stimulation (EFS)
      induced biphasic contractions of the vas deferens in order to evaluate the effect
      of varicocele on the motility of the vas deferens. MATERIAL AND METHODS: A total
      of 26 Sprague-Dawley rats (200-250 g) were assigned randomly into two groups:
      sham (n = 10) and varicocele (n = 16). Varicocele was produced by partial
      obstruction of the left renal vein. Four weeks after the surgical procedure, vasa
      deferentia were harvested and EFS-induced responses were recorded from the strips
      prepared from ipsilateral and contralateral sides via Grass isometric force
      displacement transducers. Exogenous alpha-beta methyl ATP was applied at the
      concentration of 10(-5)M to the vasa deferentia strips, and exogenous
      noradrenalin was applied cumulatively at the concentrations between 10(-7) and
      10(-4)M. At the end of each experiment, 80 mM KCl was applied to induce
      contractions. All contractions were expressed as the percentage of the 80 mM KCl
      induced contractions. RESULTS: Varicocele significantly inhibited both phases of
      EFS-induced biphasic contractions in the ipsilateral side, whereas in the
      contralateral site it did not produce any change. However, there was no change in
      exogenously applied alpha-beta methyl ATP, noradrenalin and KCl-evoked
      contractions of the vasa deferentia obtained from both sides. CONCLUSIONS: These
      results suggest that varicocele affects the ipsilateral vas deferens motility by
      reducing neurotransmitter release.

PMID- 17495478
TI  - CITES proposal highlights rarity of Asian nocturnal primates (Lorisidae:
      Nycticebus).

PMID- 17495479
TI  - The response of adult orang-utans to flanged male long calls: inferences about
      their function.
AB  - Flanged male orang-utans emit loud vocalizations called long calls. In this
      study, we examined the correlates of variation in long-calling rates among
      flanged male Sumatran orang-utans, as well as the ranging responses of adult
      females and flanged males to these long calls. Males that gave calls more often
      were more likely to approach calls by others. Results bolster a female attraction
      function of long calls. Flanged males did not significantly avoid or approach
      long calls. However, males called more when alone than when guarding a female
      mate, and adult females significantly approached long calls, especially those of
      the dominant male, and did so regardless of their reproductive state, allowing
      them to remain within earshot of calling males. The possible selective advantages
      of this response include avoidance of harassment and infanticide by males. These
      findings confirm the existence of some form of social organization above the
      mother-infant unit.

PMID- 17495480
TI  - Upper extremity function, an independent predictor of adverse events in
      hospitalized elderly.
AB  - OBJECTIVE: To examine the relationships between upper extremity function (UEF)
      and mortality, need for social assistance and change of residence, at discharge
      from hospital and at 1 month following discharge. METHODS: Observational, cohort
      study. SETTING: Acute Geriatric Unit of a Tertiary Teaching Hospital. SUBJECTS:
      356 Consecutive patients admitted over a 6-month period. Performance of 4 UEF
      tasks (UEFTs) was assessed by direct observation on admission, at discharge and
      at 1 month after discharge: picking up a full glass, touching the scapula,
      cutting with a knife and unfastening a button. UEF was correlated with measures
      of global physical and mental functioning, namely the Barthel index, the Lawton
      index, Holden's FAC scale and Pfeiffer's test. The association of UEF with
      adverse events such as mortality, need for social assistance and change of
      residence was also assessed. RESULTS: UEF was well-correlated with global
      functioning scales (p<0.001). Using multivariant models, the inability to perform
      3 or 4 UEFTs on admission was an independent predictor of mortality at discharge
      (OR 15.2; CI 95% 5.2-44.4) and at 1 month (OR 3.3; CI 95% 1.8-6.2), of need for
      social assistance at discharge (OR 2.1; CI 95% 1.1-4.1) and at 1 month (OR 3.3;
      CI 95% 1.1-10.1), and of change of residence at discharge (OR 3.5; CI 95% 1.2
      10.4). CONCLUSIONS: UEF, independently of global functioning, is a predictor of
      adverse events in the hospitalized elderly. Its determination by direct
      observation may be an indirect measure of global functioning during
      hospitalization, avoiding potentially biased data facilitated by caregivers.

PMID- 17495481
TI  - Premature ovarian failure.
AB  - The diagnosis of premature ovarian failure is based on the finding of amenorrhoea
      before age 40 associated with follicle-stimulating hormone levels in the
      menopausal range. Screening for associated autoimmune disorders and karyotyping,
      particularly in early onset disease, constitute part of the diagnostic work up.
      There is no role for ovarian biopsy or ultrasound in making the diagnosis.
      Management essentially involves hormone replacement and infertility treatment,
      the most successful being assisted conception with donated oocytes. Embryo
      cryopreservation, ovarian tissue or oocyte cryopreservation and in vitro
      maturation of oocytes hold promise in cases where ovarian failure is foreseeable
      as in women undergoing cancer treatments.

PMID- 17495482
TI  - Endothelin-1-induced pulmonary vasoreactivity is regulated by ET(A) and ET(B)
      receptor interactions.
AB  - BACKGROUND: Roles of endothelin (ET) receptors (R) and of the endothelium on ET-1
      induced pulmonary vasoreactivity are subjects of debate. This stems from
      endothelial ET(B)-R that can release both vasodilators and vasoconstrictors. The
      aim of this study was to evaluate the roles of the endothelium and of ET-Rs on ET
      1-induced pulmonary vasoreactivity. METHODS: Pharmacological experiments were
      performed in isolated rat lungs and in pulmonary resistance arteries. RESULTS: In
      isolated lungs, ET-1 and the selective ET(B)-R agonist sarafotoxin 6c (S6c)
      induced a similar vasoconstriction. ET-1 constriction was reduced by a selective
      ET(A)-R antagonist; however, the selective ET(B)-R antagonist had no significant
      effect. In preconstricted lungs, ET(B)-R stimulation caused mild vasodilation at
      low concentrations but severe vasoconstriction at higher concentrations. In
      isolated arteries, responses to ET-1 and S6c were not different and unaffected by
      removal of endothelium. Interestingly, concentrations of ET(A)-R and ET(B)-R
      antagonists that only mildly reduced ET-1 vasoconstriction when used alone,
      prevented maximal constriction and greatly reduced vascular sensitivity to ET-1
      when used in combination. CONCLUSION: In rat lungs, both ET(A)-R and ET(B)-R
      contribute to ET-1-induced pulmonary vasoconstriction with evidence of
      interaction between receptors. A mild vasodilator role of the endothelial ET(B)-R
      is evident only at low agonist concentration and when baseline vascular tone is
      increased.

PMID- 17495484
TI  - Physiology and pharmacology of the human ureter: basis for current and future
      treatments.
AB  - INTRODUCTION: This article sets out to be a review regarding agents that affect
      contraction and relaxation of the ureter in order to establish a basis for
      current and future treatments for upper urinary tract obstruction. MATERIAL AND
      METHODS: A complete review of the English literature using MEDLINE was performed
      between 1960 and 2007 on ureter physiology and pharmacology with special emphasis
      on signal transduction mechanisms involved in the contractile regulation of the
      human ureter. RESULTS: Activation of muscarinic and adrenergic receptors
      increases the amplitude of ureteral contractions. The sympathetic nerves modulate
      the contractions by alpha-adrenoceptors and relaxation by beta-adrenoceptors. The
      purinergic system is important in sensory/motor functions and ATP is an important
      non-adrenergic non-cholinergic (NANC) agent causing contraction. Nitric oxide
      (NO) is a major inhibitory NANC neurotransmitter causing relaxation. Serotonin
      causes contraction. Prostaglandin-F(2)alpha contracts whereas prostaglandin
      E(1)/E(2) relaxes the ureter. Phosphodiesterases (PDE) and the Rho-kinase pathway
      have recently been identified in the human ureter. PDE-IV inhibitors, K(+)
      channel openers, calcium antagonists, alpha(1)-adrenoceptor antagonists and NO
      donors seem to be promising drugs in relieving obstruction and facilitating stone
      passage. CONCLUSIONS: Further understanding of the ureteral function and
      pharmacology may lead to the discovery of promising new drugs that could be
      useful in relieving ureteral colic, facilitating spontaneous stone passage,
      preparing the ureter for ureteroscopy as well as acting adjunctive to
      extracorporeal shock-wave lithotripsy.

PMID- 17495485
TI  - Impact factors in urology. How well do our journals stack up against other
      medical and surgical journals?
AB  - INTRODUCTION: The purpose of our analysis was to assess the performance of
      urological journals in terms of the standardized measures created by the
      Institute of Scientific Information (ISI) Journal Citation Report (JCR) in
      comparison to other medical and surgical fields. Additionally, an evaluation of
      all original articles, clinical or experimental, published in the year 2005,
      assessing the time interval needed from submission to publication, submission to
      acceptance, and acceptance to publication of a manuscript was conducted for all
      urologic journals. MATERIALS AND METHODS: The study was conducted with the help
      of the ISI JCR and the University of Erlangen Medical Center's library (and on
      line library). RESULTS: The field of urology demonstrates satisfactory measures
      created by the (ISI) JCR in comparison with various fields of medicine. In
      comparison with the surgical field, urological journals demonstrate outstanding
      results. DISCUSSION: The impact factor is a measure of the importance of
      scientific journals. Urological journals stack up quite well against other
      medical and especially surgical journals.

PMID- 17495486
TI  - Chronic hypoxia, physical exercise and PSA: correlation during high-altitude
      trekking (2004 K2 expedition).
AB  - The aim of the present study was to identify the effects of physical exercise on
      PSA serum levels and the diagnostic validity of PSA in the screening of prostate
      cancer in subjects undergoing physical exercise during chronic hypoxia. The study
      was performed during trekking between 3,200 and 5,600 meters of altitude on K2
      mountain for 26 days. Mean serum PSA values before and after exposure did not
      show significant difference due to physical exercise. These data indicate that
      physical exercise or mountain hypoxia do not affect the diagnostic validity of
      PSA.

PMID- 17495487
TI  - Prevalence and clinical significance of prostate cancer among 12,682 men with
      normal digital rectal examination, low PSA levels (< or =4 ng/ml) and percent
      free PSA cutoff values of 15 and 20%.
AB  - AIM: To report prevalence and clinical relevance of T1c prostate cancers (PCa) in
      a selected population of men with serum prostate-specific antigen (PSA) levels <
      or =4 ng/ml enrolled in a multicenter case-finding protocol. PATIENTS AND
      METHODS: A number of 16,298 men, aged 40-75 years, from the urology units they
      had been referred to, in most cases (81.6%) for lower urinary tract symptoms,
      were evaluated. Eighty percent of them had PSA < or =4 ng/ml and about 40% PSA <
      or =2.5 ng/ml. Patients with PSA < or =2.5 ng/ml and PSA between 2.6 and 4 ng/ml
      and with percent free PSA < or =15 and < or =20%, respectively, were eligible for
      biopsy; 28 patients refused it, and 11 patients were excluded from the study
      because of an abnormal digital rectal examination. Among 403 biopsied men, 82 had
      PSA < or =2.5 ng/ml (group A) and 321 PSA between 2.6 and 4 ng/ml (group B).
      RESULTS: A PCa was found in 109 cases (27.0%): 21 in group A and 88 in group B.
      48 (44%) of the 109 patients with a PCa underwent radical prostatectomy: all
      cancers had a volume >0.5 cm(3), and 41% had a final Gleason sum > or =7; the PCa
      was organ confined in 34 patients (70.8%) and locally advanced in 14 patients
      (29.1%), and in 12 patients (25%) positive surgical margins were found.
      CONCLUSIONS: Using percent free PSA thresholds of 15 and 20%, 25.6% of the men
      with PSA < or =2.5 ng/ml and 27.4% of the men with PSA between 2.6 and 4 ng/ml
      were found to have a PCa, respectively. Most of these cancers, when submitted to
      radical prostatectomy, were found to be clinically significant. As these cancers
      are mostly organ confined, these patients are ideal candidates for curative nerve
      sparing surgery.

PMID- 17495488
TI  - Impact of additional sampling in the TRUS-guided biopsy for the diagnosis of
      prostate cancer.
AB  - AIM: To evaluate the diagnostic value of 10+ systematic sampling technique when
      performing transrectal ultrasound-guided (TRUS) prostate biopsy, compared with
      the sextant biopsy technique for patients with suspected prostate cancer.
      METHODS: 286 patients with suspected prostate cancer were included in the study.
      Patients were eligible for the study if they had serum levels of prostate
      specific antigen (PSA) >4 ng/ml or ratio PSA <0.25 and/or an abnormal digital
      rectal examination (DRE). The population sample was divided in three groups: (1)
      those with positive PSA, PSA ratio and DRE (70 patients); (2) those with positive
      PSA and PSA ratio but normal DRE (178 patients), and (3) those with positive PSA
      and PSA ratio, positive PSA velocity and a negative biopsy in the previous 6
      month period (38 patients). In addition to the conventional sextant prostate
      biopsy cores, four more biopsies were obtained from the lateral peripheral zone
      (10 core biopsy protocol). Additional cores (total of 12-14) were also randomly
      selected in case of larger prostates (>60 ml) or from suspicious foci revealed by
      transrectal ultrasound. All additional biopsy cores were submitted separately to
      the pathological department. RESULTS: Cancer was detected in 55.7% (39/70) and
      69% (48/70) of the patients (for sextant core and for the extended biopsy
      protocols, respectively) in the first study group, 11% (20/178) and 23% (41/178)
      of the patients (for the sextant and the extended biopsy protocols, respectively)
      in the second study group, and 42% (16/38) and 63% (24/38) of the patients (for
      the sextant and the extended biopsy protocols, respectively) in the third study
      group. The addition of the lateral peripheral zone (PZ) of the prostate to the
      sextant biopsy showed a 23, 105 and 50% increase in the number of cancers
      diagnosed in the first, second and third study groups, respectively. The
      improvement of cancer detection rate (sensitivity) was statistically significant
      for all groups evaluated. CONCLUSION: The 10+ systematic TRUS-guided prostate
      biopsy improves the detection rate of prostate cancer compared to the sextant
      biopsy technique alone, especially when performed in men with positive PSA, PSA
      ratio, and negative DRE.

PMID- 17495489
TI  - Patients with low prostate-specific antigen levels (< or =4 ng/ml) would benefit
      from a twelve-core biopsy protocol for prostate cancer detection.
AB  - INTRODUCTION: Prostate biopsy protocols using twelve cores rather than the
      standard six cores have consistently shown improved prostate cancer detection
      rates. The aim of our study was to evaluate whether the improved rate of prostate
      cancer detection in patients with low prostate-specific antigen levels warrants
      the standardization of a twelve-core biopsy protocol in this group. PATIENTS AND
      METHODS: The clinical and pathological records from 241 patients treated between
      2000 and 2003 were evaluated, and the impact of a twelve-core biopsy protocol on
      the prostate cancer detection rate relative to prostate-specific antigen levels
      compared to the standardized six-core biopsies was analyzed. RESULTS: Prostate
      cancer was detected in 34% (81/241) of the patients who underwent transrectal
      ultrasound-guided biopsy. An additional 23.5% (19/81) of the carcinomas were
      diagnosed using the twelve-core biopsy protocol, and 84.2% (16/19) of these
      fulfilled the clinical significance criterion developed by Epstein and coworkers
      (see text). Interestingly, the greatest increase was found in the patient group
      with prostate-specific antigen levels < or =4 ng/ml. CONCLUSIONS: Patients with
      low prostate-specific antigen levels (< or =4 ng/ml) would benefit from the
      standardized use of a twelve-core biopsy protocol using peripheral cores.

PMID- 17495490
TI  - Transrectal ultrasound versus magnetic resonance imaging in the estimation of
      prostate volume as compared with radical prostatectomy specimens.
AB  - INTRODUCTION: There are relatively few studies that compare the use of
      transrectal ultrasound (TRUS) to magnetic resonance imaging (MRI) to estimate the
      prostate volume. In this study, we compared the prostate volumes measured with
      MRI and TRUS with a surgical specimen volume. PATIENTS AND METHODS: Seventy-three
      patients underwent TRUS examination of the prostate prior to radical
      prostatectomy. All specimens were weighed and measured when freshly excised. The
      corresponding volume measurements calculated using TRUS and MRI were compared
      retrospectively with the measured volumes of freshly excised prostate. RESULTS:
      The volume measured with TRUS and MRI was linearly related to the radical
      prostatectomy volume. The estimated increase in the prostate volumes measured
      with TRUS and MRI per specimen volume was 0.9508 and 0.9331 by regression
      analysis, respectively. If the prostate volumes were <35 cm(3), the prostate
      volumes measured with MRI overestimated the specimen volumes. If the prostate
      volumes were >35 cm(3), the prostate volumes measured with MRI underestimated the
      specimen volumes. The classic ellipsoid formula was adequate for determining the
      prostate volume. CONCLUSIONS: In this study, MRI and TRUS gave different volumes.
      MRI is more accurate than TRUS for determining the prostate volume. However,
      because TRUS is inexpensive, noninvasive, and almost as accurate as MRI, it
      should be the preferred method for measuring the prostate volume.

PMID- 17495491
TI  - Percentage of cancer in prostate biopsies as prognostic factor for staging and
      postoperative biochemical failure after radical prostatectomy.
AB  - OBJECTIVE: To assess if the percentage of cancer in prostate needle biopsies
      provides independent prognostic information for predicting pathological stage
      and/or biochemical relapse after radical prostatectomy. METHODS: One hundred and
      forty prostate cancer patients who underwent radical prostatectomy were
      evaluated. Preoperative parameters analyzed were patient age, PSA, clinical
      stage, and the information obtained from sextant biopsies (Gleason score, maximum
      percentage of cancer in a core, percentage of tissue with cancer in all biopsies
      and the number of cores positive for cancer). Univariate and multivariate
      analyses (logistic regression) for the dependent variables (prostate cancer,
      organ-confined and biochemical relapse) were performed. RESULTS: The tumor was
      organ-confined in 73.6% of patients. In those patients studied for disease
      progression (n = 126), no biochemical recurrence was observed in 76.2%. In the
      multivariate analysis for organ-confined disease, the total percentage of biopsy
      tissue with cancer, the preoperative PSA level, the Gleason score and the
      clinical stage were the most accurate predictive factors of pathological stage.
      The multivariate analysis for the study of biochemical failure indicated that
      only the total percentage of biopsy tissue with cancer, the preoperative PSA
      level and the Gleason score were independent predictive factors. According to the
      logistic regression analysis for disease recurrence, 3 risk groups could be
      identified: low risk (less than 10% probability of disease progression),
      intermediate risk (30%) and high risk (more than 70%). CONCLUSIONS: The
      percentage of cancer in prostate biopsy provides independent prognostic
      information for predicting pathological stage and the risk of biochemical failure
      after radical prostatectomy.

PMID- 17495492
TI  - Prostate cancer screening with prostate-specific antigen in hemodialysis
      patients.
AB  - BACKGROUND/AIMS: The diagnostic validity of prostate-specific antigen (PSA) among
      men receiving hemodialysis (HD) has not been well defined. The aim of this study
      was to evaluate PSA levels in HD men and to compare them with those of non-uremic
      controls. METHODS: PSA levels were measured in 620 HD men (40-89 years old, mean
      age 62.4 years). In patients with PSA >4.1 ng/ml, prostate biopsies were
      performed. Cancer-free men were defined as having PSA ranging between 0 and 4.0
      ng/ml, or PSA >4.1 ng/ml but with a pathologically negative biopsy. The resulting
      data was compared with that for 3,636 non-uremic controls (55-59- (n = 468), 60
      69- (n = 2,220), and 70-79-year-old men (n = 948)). RESULTS: Of 45 HD men with
      PSA >4.1 ng/ml, 22 consented to undergo a biopsy. Ten were positive and 12 were
      negative. The mean PSA of cancer-free HD men of 50-59 (n = 159), 60-69 (n = 214),
      70-79 (n = 116), and 80-89 (n = 30) were 1.0, 1.0, 1.3, and 2.1 ng/ml,
      respectively. Cancer-free HD men demonstrated significantly lower PSA compared to
      controls. CONCLUSIONS: HD men had lower PSA levels than those of controls.

PMID- 17495493
TI  - Comparison of 1998 WHO/ISUP and 1973 WHO classifications for interobserver
      variability in grading of papillary urothelial neoplasms of the bladder.
      Pathological evaluation of 258 cases.
AB  - AIM: Our aim was to compare the interobserver variability between the 1998
      WHO/ISUP and 1973 WHO classifications. METHODS: 258 consecutive papillary
      urothelial carcinomas were reviewed by two pathologists and assigned a tumor
      grade according to the 1973 WHO and 1998 WHO/ISUP without the knowledge of
      primary diagnosis and clinical follow-up. All cases were also histologically
      staged by the two pathologists separately as follows: pTa (noninvasive), pT1
      (lamina propria invasion only), pT2 (muscularis propria invasion). Findings of
      both pathologists and degree of agreement were compared statistically by using
      Pearson's chi(2) test and kappa statistics respectively. A kappa value of 0.21
      0.40 is accepted as fair, 0.41-0.60 moderate and 0.61-0.80 substantial agreement.
      RESULTS: Regardless of the pathologist, tumor grades of two classifications
      correlated to each other and the pathological stage (p < 0.05). Overall degree of
      agreement between pathologists was higher in the 1998 WHO/ISUP (kappa 0.59) than
      the 1973 WHO (kappa 0.41), but both were still moderate. Papillary urothelial
      neoplasia with low malignant potential was the group of 1998 WHO/ISUP that showed
      the lowest degree of agreement and if excluded, interobserver variability of the
      1998 WHO/ISUP decreased significantly (kappa 0.84). CONCLUSION: The diagnosis of
      papillary urothelial neoplasia with low malignant potential and the criteria that
      differentiates it from low-grade carcinomas needs improvement in order to compare
      the different studies and therapies and to provide more accurate information for
      management.

PMID- 17495494
TI  - Palliative treatment of bone metastases in hormone-refractory prostate cancer:
      effects of pamidronate on the carboxyterminal telopeptide of type-I collagen
      level in patients with increasing prostate-specific antigen levels.
AB  - PURPOSE: Bisphosphonates have been reported to be effective in reducing bone pain
      and skeletal-related events associated with bone metastases in hormone-refractory
      prostate cancer (HRPC). However, whether bone resorption is reduced primarily by
      these particular drugs is difficult to evaluate because patients with HRPC are
      usually treated with secondary or tertiary hormonal manipulations including
      second-line antiandrogens, high-dose diethylstilbestrol, or low-dose
      dexamethasone therapies, some of which may also be effective. Thus, we assessed
      changes in the level of the carboxyterminal telopeptide of type-I collagen
      (ICTP), a bone resorption marker, before and after pamidronate administration in
      HRPC patients with increasing prostate-specific antigen (PSA) levels. PATIENTS
      AND METHODS: Twenty-one HRPC patients with bone metastases and increasing PSA
      levels were intravenously treated with pamidronate at a dose of 30 mg either
      every 2 or every 4 weeks. Pamidronate administration was started immediately
      after confirmation of three consecutive increases in the PSA level. RESULTS: In
      14 patients (67%), the ICTP levels decreased after the administration of
      pamidronate, despite increasing PSA levels. In 7 of these cases, the ICTP levels
      were lower than those recorded for 6 months or longer before the start of
      pamidronate administration. The characteristics of the responders were compared
      with those of the non-responders. CONCLUSION: In 67% of the HRPC patients with
      increasing PSA levels, pamidronate reduced the accelerated turnover of bone
      metabolism caused by metastases of prostate cancer.

PMID- 17495495
TI  - Effect of patient position on pain experienced during prostate biopsy.
AB  - OBJECTIVES: To compare pain during prostate biopsy performed in two different
      positions. METHODS: We carried out a prospective, randomized study to compare the
      pain experienced during biopsy in two different positions: lithotomy (group 1)
      and lateral (group 2). Pain was evaluated using a visual analog scale (VAS).
      RESULTS: 70 patients were randomized to the two positions for biopsy. The median
      number of samples taken was the same for both groups (n = 10). The median VAS
      rating after biopsy was 30 in group 1 and 45 in group 2. 96.6% of the men in
      group 1 were prepared to undergo a repeat examination according to the same
      modalities, against only 86.7% in group 2. Only 14.3% of the men in group 1 would
      have preferred more analgesic against 37.1% in group 2. Pain after biopsy was
      less in group 1. The men with prostate adenocarcinoma tolerated biopsies better
      than the others. CONCLUSION: Our results suggest that the lithotomy position
      induced less pain and less post-biopsy hematuria than did the lateral position
      during prostate biopsy. Men with prostate adenocarcinoma tolerated the procedures
      better.

PMID- 17495496
TI  - Protective effects of trimetazidine on testicular ischemia-reperfusion injury in
      rats.
AB  - INTRODUCTION: We tried to prove the effectiveness of trimetazidine (TMZ) on
      testicular torsion-detorsion injury. MATERIALS AND METHODS: 15 male rats were
      equally divided into three groups: group 1 was the sham-operated control group;
      group 2 had 2 h of unilateral testicular ischemia followed by 3 days of
      reperfusion, and group 3 had 2 h of unilateral testicular ischemia followed by 3
      days of oral TMZ treatment (5 mg/kg, bid) during reperfusion. In the removed
      testicles, tissue reduced glutathione (GSH), glutathione reductase (GR),
      glutathione peroxidase (GPx), malondialdehyde (MDA) levels and pathological
      modified Johnson scores (MJS) were evaluated. Mann-Whitney U test was used for
      statistical evaluations. RESULTS: In group 2, on the ipsilateral side, GSH were
      significantly lower and MDA were higher than in groups 1 and 3, though GSH and
      MDA were not statistically different between groups 1 and 3. On the other hand,
      GPx in the control testicles of group 3 was significantly lower compared to those
      in the counterparts of both groups 1 and 2. Among three groups, GR determined in
      both testicles were not statistically different. On the ipsilateral side, MJS in
      group 3 were lower than in the sham group, but significantly higher than in group
      2. CONCLUSIONS: According to this study, TMZ has an antioxidant effect on
      testicular torsion-detorsion injury, though the protective effect of TMZ seems to
      decrease in control testicles. Consequently it has been considered that TMZ can
      be only used in torsion patients with a healthy contralateral testicle after
      further studies have been conducted.

PMID- 17495497
TI  - The real diagnosis of cystinuria.

PMID- 17495498
TI  - Synchronous epidermoid cyst and mature teratoma of the testis: an unusual
      association.
AB  - We describe here the first case of a synchronous epidermoid cyst and mature
      teratoma of the testis occurring in a young man presenting a with bilateral
      testicular tumor. After a clinical, biological and ultrasound evaluation, testis
      sparing surgery was performed on the left testis and a total orchiectomy on the
      right side in accordance with oncological principles. Histopathological
      examination revealed a simple epidermoid cyst on the left side and a mature
      teratoma on the right side, following Price's criteria. No metastasis was
      detected, and the patient was closely followed. The patient remains disease-free
      and has normal postoperative testosterone levels 3 years after the surgery.

PMID- 17495499
TI  - Seminal vesicle-rectal fistula with preceding right acute epididymitis.
AB  - A case of seminal vesicle-rectal fistula is reported. A 74-year-old Japanese man
      was admitted to our hospital due to repeated right scrotal swelling and high
      fever with pneumaturia. A diagnosis of the right acute epididymitis was made.
      Bilateral vesiculography showed contrast medium leakage to the rectum, and
      colonoscopy revealed ostium of the fistula in the anterior wall of the rectum.
      Symptoms were improved by extirpation of the right scrotal contents.

PMID- 17495500
TI  - Bilateral percutaneous nephrolithotomy in a patient with hemophilia A disorder.
AB  - A 50-year-old man with hemophilia A presented with recurrent hematuria due to
      renal stone disease. He was receiving approximately 50,000 units of recombinant
      factor (rF) VIII concentrate every year due to hematuria. Between 1996 and 2002,
      his serum creatinine level increased from 0.7 to 1.2 ng/ml. In an effort to
      resolve the problems of excessive blood loss with transfusions, recurrent rF VIII
      replacements and deteriorating renal function, he was offered treatment with
      percutaneous nephrolithotomy (PNL) in conjunction with rF VIII administration. He
      underwent left PNL for left staghorn calculi in November 2002 with administration
      of 52,000 units rF VIII, and another PNL for the right kidney in April 2004 with
      the administration of 90,500 units rF VIII. A pneumatic lithotriptor was used in
      both operations. The serum creatinine level was 0.8 ng/ml upon completion of
      treatment and the patient was symptom and stone free at 10-month follow-up. He
      has not suffered from hematuria since that time. We conclude that bleeding
      disorders may not be a contraindication for PNL if corrected and monitored
      appropriately.

PMID- 17495501
TI  - Synchronous endoscopic management of bilateral kidney and ureter fungal bezoar.
AB  - Candidiasis of the lower urinary tract is common in immunocompromised patients.
      Diabetes and chronic indwelling catheter are two common risk factors for such
      opportunistic infections. However, upper urinary candidiasis is rare. Further,
      bilateral synchronous involvement of kidneys and ureter is extremely rare.
      Treatment usually requires relief of obstruction by percutaneous drainage of the
      kidney and systemic infusion or local irrigation of antifungal agents. When these
      measures fail, percutaneous surgical debulking of the fungal bezoar is indicated.
      We present a case of obstructive anuria due to fungal bezoar in both the
      pelvicalyceal system and ureter managed by bilateral synchronous endoscopic
      removal of fungal bezoar.

PMID- 17495502
TI  - Painting after right-hemisphere stroke - case studies of professional artists.
AB  - Changes in the style of professional artists as an immediate consequence of
      cerebrovascular disease are an intriguing phenomenon for the neuroscientist.
      While left-hemisphere damage is commonly provoking alterations in verbal
      production and comprehension, right-hemisphere stroke often leads to left-sided
      visuospatial neglect. We present a case series of 13 professional artists with
      right-hemisphere stroke and compare examples of their poststroke artwork with
      their prestroke artwork.

PMID- 17495503
TI  - I and me: self-portraiture in brain damage.
AB  - Human bodily experience is characterized by the immediate feeling that our body
      is localized at a certain position in space and that the self is localized within
      these body borders (embodiment). Recent research from cognitive neuroscience and
      neurology suggests that embodiment is of major importance for neuroscientific
      models of self and self-consciousness. This is suggested by illusory own body
      perceptions (such as autoscopic hallucinations, heautoscopy, and out-of-body
      experiences) during which the self may be experienced as being localized outside
      one's body borders. I have previously argued that self-portraiture may rely on
      similar brain mechanisms and have proposed a classification of self-portraiture
      based on neurological classifications of illusory own body perceptions. Here I
      extend this model focussing on three types of self-portraits: visual self
      portraits, disembodied self-portraits, and corporeal self-portraits. This is
      followed by a discussion of visuospatial, linguistic, and mnestic mechanisms in
      self-portraiture that are examined in selected painters.

PMID- 17495504
TI  - Lovis Corinth: integrating hemineglect and spatial distortions.
AB  - Lovis Corinth suffered a right-hemispheric stroke at the age of 53 years, but
      died only 14 years later. The huge number of artworks that he produced after this
      life-threatening disease allows a detailed analysis of his poststroke artwork in
      comparison to his prestroke artwork. When performing this analysis as a
      neurologist, an enormous diversity of subtle stroke sequelae can be discovered,
      which can mostly be explained by a left-sided hemineglect. These findings clearly
      go far beyond pure psychological processes. Moreover, Corinth is a good and
      motivating example for patients suffering disability after a stroke, because he
      was able to produce great artwork after his stroke. Lovis Corinth was struggling
      against motor disability that admittedly was not severely affecting his artistic
      production but he also had to fight against severe neuropsychological deficits
      that did have clear consequences for his artistic production. Corinth's credo was
      'true art means to use unreality'. Taken together with the often cited phrase of
      'drawing means to [details]', there will be a clear-cut interpretation for the
      neurologist that can be derived from the understanding of a right-hemisphere
      lesion and subsequent left-sided neglect.

PMID- 17495505
TI  - Visconti and Fellini: from left social neorealism to right-hemisphere stroke.
AB  - The acclaimed Italian directors Luchino Visconti and Federico Fellini had very
      different life trajectories that led them to become major figures in the history
      of cinema. Similarities, however, can be found in their debuts with the
      neorealist genre, their personalities, creative styles and politicocultural
      involvement, and ultimately in the neurological disease that struck them at the
      end of their careers. Both suffered a right-hemispheric stroke that left them
      hemiplegic on the left side. We review their life and career to put that event
      into perspective, and then discuss its aftermath for both artists in the light of
      our current knowledge of right-hemispheric functions. Visconti showed a
      tremendous resilience following the accident and managed to direct several films
      and plays as an infirm, whereas Fellini had to put an end to his career but still
      was able to display his talents to the neuropsychologists that treated him. A
      speculative account is given of the links between right-hemispheric
      symptomatology and the premorbid personality of these highly prolific patients.

PMID- 17495506
TI  - De novo artistic behaviour following brain injury.
AB  - The effect of brain injury and disease on the output of established artists is an
      object of much study and debate. The emergence of de novo artistic behaviour
      following such injury or disease, while very rare, has been recorded in cases of
      frontotemporal dementia, epilepsy, subarachnoid haemorrhage and Parkinson's
      disease. This may be an underdiagnosed phenomenon and may represent an
      opportunity to further understand the neural bases of creative thought and
      behaviour in man and those of cognitive change after brain injury. There is
      clearly an important role for hemispheric localization of pathology, which is
      usually within the temporal cortex, upon the medium of artistic expression, and a
      likely role for mild frontal cortical dysfunction in producing certain
      behavioural and cognitive characteristics that may be conducive to the production
      of art. Possible mechanisms of 'artistic drive' and 'creative idea generation' in
      these patients are also considered. The increased recognition and responsible
      nurturing of this behaviour in patients may serve as a source of great comfort to
      individuals and their families at an otherwise difficult time.

PMID- 17495507
TI  - Marcel Proust's diseases and doctors: the neurological story of a life.
AB  - Marcel Proust (1871-1922), one of the greatest writers of all times, suffered
      from asthma beginning at age 9, in an era when the illness was considered a
      'nervous' disorder belonging to what Beard, in 1870, called 'neurasthenia'.
      Proust's father, Adrien, was himself a professor of medicine (hygiene) who had
      met Charcot, and who contributed to neurology with studies on aphasia, stroke,
      hysteria, and neurasthenia - a condition about which he, along with Gilbert
      Ballet, published a book in 1897. Through his father, Proust met Edouard
      Brissaud, the co-founder of the Revue Neurologique in 1893, and, in 1896, the
      author of The Hygiene of the Asthmatics, with a foreword by Adrien Proust.
      Shortly after his mother's death in 1905, Proust contemplated admitting himself
      to a private hospital to reset his irregular sleep patterns and to improve his
      asthma. He hesitated in his choice of care between Jules Dejerine in Paris, Henry
      Auguste Widmer at Valmont, and Paul Dubois in Bern. Finally, he decided to enter
      Paul Sollier's clinic, in Boulogne-sur-Seine, on the advice of Brissaud, and
      stayed there for 6 weeks in semi-isolation. Together with Babinski, Sollier was,
      at that time, considered the most gifted follower of Charcot. He was a forerunner
      of studies on emotional memory, which strongly influenced Proust. In Proust's
      opus magnum work In Search of Lost Time, 'involuntary memory' indeed forms the
      core mechanism of the entire novel, counterbalancing the decaying effects of
      time. A few years before his death from complicated bronchopneumonia at age 52,
      Proust became terrified of developing a stroke, like his mother and father, and
      he consulted with Joseph Babinski, who tried to reassure him. Proust's life
      followed an unusual neurological itinerary, which has been largely overlooked,
      but which is in fact critical for an understanding of his literary work.

PMID- 17495508
TI  - Heinrich Heine and syphilis.
AB  - Though Heinrich Heine died 151 years ago, the underlying illness responsible for
      his suffering of many years has never been fully clarified. The diagnosis put
      forward most frequently in retrospect was that of a venereal disease. However,
      this diagnosis was the result of an interpretation in disregard of the historical
      context. Only by evaluating and interpreting the entire source material in its
      historical context (Heine's complete works, his correspondence, records of
      conversations kept by contemporaries and prescriptions) can this diagnosis be
      confirmed on a reliable basis. Above all, medical records dated 1848 and their
      interpretation in the context of contemporary syphilis nosology and therapy show
      that Heinrich Heine was treated for syphilis from 1848 onward. After 8 years
      confinement to the proverbial 'mattress grave', Heine's death can ultimately be
      explained by his long-standing and well-documented abuse of opium.

PMID- 17495509
TI  - Baudelaire's aphasia: from poetry to cursing.
AB  - At 45 years of age, Charles Baudelaire suffered a left hemispheric stroke that
      left him with a right hemiplegia and severe aphasia. In this chapter, we
      investigate the nature of his symptoms, drawing mostly on his own and his
      contemporaries' correspondence. Before specifically examining his aphasia, we put
      the poet's life, work, and health in context, notably his tormented mind, his
      probable syphilitic infection and the intellectual milieu of 19th century France.
      The time when Baudelaire was struck with aphasia coincides with early discoveries
      and debates that centered on the nature and implications of this neurological
      disorder. Many of the questions raised at that time still await definitive
      answers. Here, we compare Baudelaire's language disorder with recent research
      that has shed new light on the poet's disease. Most interestingly, we explore the
      nature of his dramatic use of the expletive Cre nom!, which was the only word he
      was able to express. Finally, we discuss the links between disease and creativity
      and dismiss the frequent notion that Baudelaire, in the end, paid the price of
      his genius.

PMID- 17495510
TI  - Memory and the creation of art: the syndrome, as in de Kooning, of 'creating in
      the midst of dementia'.
AB  - The creation of abstract art demands high intellectual capacities. Willem de
      Kooning, nonetheless, accomplished his last paintings while crippled by
      impairments diagnosed as Alzheimer's disease. Until my research neither art nor
      science offered an explanation, or a thinking method, for identifying this
      phenomenon, for solving a mystery that pertains to human discovery and creation.
      In this 'ArtScience' study of the de Kooning phenomenon I use 'Thinking Methods'
      which I devised by a systematic application of information on the workings of the
      brain, the 'Brain Methods'. With my 'Method of Observation' I examined de
      Kooning's paintings, created both before and during dementia, and found them
      comparable in technique and expression. This demonstrates the authenticity of art
      created in dementia. With my 'Cognitive Analysis' I identified in de Kooning the
      syndrome herein called 'Creating in the Midst of Dementia'. This Syndrome, unique
      in mechanisms and presentation, is characterized by (1) a specific combination of
      brain functions and malfunctions, in this case, preservation of three memory
      systems - working, procedural, and episodic - and deficit of the semantic memory
      system, and by (2) a response to precise stimuli, one that triggers brain
      reactivation, and as a consequence enables creating in the midst of dementia. My
      work offers: (1) The identification of the 'Syndrome of Creating in the Midst of
      Dementia'. It (a) presents its definition, the criteria of diagnosis, mechanism,
      rationale, and possibility of 'cognitive repair' and (b) solves the mystery of de
      Kooning creating art while crippled by dementia. (2) New Thinking Methods, the
      'Brain Methods', that based on information on the workings of the brain, open a
      new path in the pursuit of truth. The 'Method of Observation' serves to define
      stimuli, and the 'Cognitive Analysis' to assess cognitive faculties. (3) The
      integration of art and science into a new discipline of study, 'ArtScience'.

PMID- 17495511
TI  - Persisting aphasia, cerebral dominance, and painting in the famous artist Carl
      Fredrik Reutersward.
AB  - What about artistic creativity following a cerebral lesion? We studied the case
      of a prominent right-handed Swedish painter and sculptor who suffered a cerebral
      hemorrhage at the age of 55 years. The patient displayed a lesion of the left
      capsular lenticular region, which resulted in a right hemiplegia and sensory
      loss, with aphasia of the subcortical type. The linguistic impairments recovered
      well but at 1 year postonset, the right hand was still completely paralyzed.
      After a period of a few weeks, during which the patient refused to use his
      nondominant hand, he produced his first left-handed drawing, and by 1 year
      postonset, he had once again resumed an intensive artistic activity using his
      nondominant hand. The pictorial works were reviewed by several renowned art
      specialists: changes of style and even of contents were judged without loss of
      artistic quality. The result was described as a gain in emotional and artistic
      intensity. We discuss our observation in the context of the literature and focus
      on the crucial role of cerebral dominance and hand preference. We conclude that
      pictorial creativity and language are distinct forms of expressions.

PMID- 17495512
TI  - Mozart in the neurological department - who has the tic?
AB  - In Wolfgang Amadeus Mozart's medical history quite an impressive list of possible
      diseases has been collected. In the 1980s the diagnosis of Tourette's syndrome
      was added to the list. Evidence of vocal tics was derived from the scatological
      expressions found in the letters of Mozart. In addition there are a few
      contemporary reports on striking motor behavior suggesting the existence of motor
      tics. However, in a critical light the arguments for the diagnosis are quite
      weak. Most problematic is the concept that involuntary vocal utterances are
      transferred to the written form. One would expect to find similar written
      manifestations of vocal tics in the work of authors suffering from Tourette's
      syndrome. This is neither the case in the work of Samuel Johnson (1709-1784) nor
      in that of Andre Malraux (1901-1976). In conclusion, Tourette's syndrome is an
      inventive but implausible diagnosis in the medical history of Mozart.

PMID- 17495513
TI  - Hans von Bulow: creativity and neurological disease in a famous pianist and
      conductor.
AB  - Hans von Bulow (1830-1894) was a conductor and pianist of worldwide reputation
      and founder of many stylistic interpretations of classic and romantic symphonies.
      The close friendship with Richard Wagner, but not the enthusiastic admiration of
      his dramatic musical opus, ended abruptly when Hans von Bulow became aware of the
      betrayal of his wife Cosima and Richard Wagner. Hans von Bulow reported symptoms
      and signs of neurological disease in many letters that were kept and edited by
      his second wife Marie. For decades he suffered from chronic neuralgiforme
      headaches, which were caused by a tumor of the cervical radicular nerves. At the
      age of 45 years, he suddenly developed a motorsensory deficit in the right arm
      and hand and a contralateral facial deficit, suggestive of brainstem infarction.
      He recovered and celebrated even greater successes as a musician, although phases
      of major depression also interfered with his professional life. In the last,
      phase of his life, he experienced the consequences of generalized atherosclerosis
      and cerebral microangiopathy. It was a second cerebrovascular accident of the
      brainstem that caused his death, only 10 months after his last concert
      performance. Although his death occurred in Egypt, an autopsy was performed by
      Professor Ludwig Edinger and the results will be presented.

PMID- 17495514
TI  - Synaesthesia, the arts and creativity: a neurological connection.
AB  - For over 100 years the link between synaesthesia and the arts has attracted
      controversy. This has been spurred by the production of auditory, literary and
      visual art by famous individuals who report experiences synonymous with the
      neurological condition. Impressive protagonists in this discussion include Arthur
      Rimbaud, Charles Baudelaire, Vasily Kandinsky, Vladimir Nabokov, Alexander
      Scriabin, Olivier Messiaen and David Hockney. Interdisciplinary debates have
      concerned whether synaesthesia can actively contribute to an artist's ability,
      whether it is a driving force or a mere idiosyncratic quirk and whether,
      fundamentally, it is a distinct idiopathic condition or an unusual metaphorical
      description of normal perception. Recent psychological and neuroscientific
      evidence offers a new level to the debate. Coherent patterns of a neural basis of
      synaesthesia have been confirmed with high spatial resolution brain imaging
      techniques and the link with the arts is transpiring to be more than superficial
      or coincidental. Moreover, the neural distinction of the synaesthete brain may
      prove to be a window into a neural basis of creative cognition, and therefore
      conducive to the expression of creativity in various media.

PMID- 17495515
TI  - The hallucinating art of Heinrich Fussli.
AB  - Der Nachtmahr (The Nightmare) was painted 1781 by the Swiss-born artist Heinrich
      Fussli (1741-1825). Neurologists, sleep medicine specialists and sleep
      researchers are familiar with this popular work, which became a symbol for the
      phenomenon of sleep paralysis. Notably, Fussli created this work decades before
      the first scientific description of the syndrome. Therefore, the following
      chapter aims to reflect the painting against the background of Fussli's
      biography, neuropsychological interpretations, and of pathophysiological and
      neurobiological considerations on sleep paralysis.

PMID- 17495516
TI  - Modulating autophagy for therapeutic benefit.
AB  - Autophagy is an ancient cell survival pathway that allows cells to recoup ATP and
      essential building blocks for biosynthesis when they are starved of nutrients or
      when they are exposed to hypoxia, which are hallmarks of the tumor
      microenvironment. This pathway involves the formation of double-membraned
      vesicles, coined autophagosomes, which envelop bulk cellular material and/or
      organelles and that subsequently fuse with lysosomes that degrade their cargo.
      Autophagy has been suggested to play important roles in chemoresistance of cancer
      to some therapeutic agents, which typically induce an apoptotic response. For
      example, the histone deacetylase inhibitor SAHA induces both apoptosis and
      autophagy, suggesting that agents that disrupt the autophagy pathway might
      augment its efficacy as a therapeutic agent. We tested this notion in a model of
      Imatinib-refractory chronic myelogenous leukemia (CML) and in imatinib-resistant
      primary CML cells from patients bearing mutations in Bcr-Abl, including the T315I
      mutation that causes resistance to currently utilized tyrosine kinase inhibitors
      and translates into a very poor clinical prognosis. Agents that disrupt autophagy
      were shown to synergize with SAHA in provoking apoptotic death of these
      refractory tumors. These findings support the use of agents that disrupt the
      autophagy pathway in settings of chemorefractory malignancies.

PMID- 17495517
TI  - Autophagy during conidiation, conidial germination and turgor generation in
      Magnaporthe grisea.
AB  - Autophagy is a ubiquitous and evolutionarily conserved process found in all
      eukaryotic cells that allows for the degradation and recycling of old proteins
      and organelles. Starvation can induce autophagy, and autophagic pathway is an
      essential process for cellular function under starvation. In Magnaporthe grisea,
      starvation is one of the key induced factors for the germ tube tip to
      differentiate into an appressorium. Considering the importance of the rice blast
      fungus as a primary model for host-pathogen interaction, the role of autophagy in
      fungal development, appressorium turgor generation and pathogenicity of M. grisea
      via its role in organelle and protein turnover is a very significant subject.

PMID- 17495518
TI  - Cathepsin D deficiency and NCL/Batten disease: there's more to death than
      apoptosis.
AB  - Animal models of cathepsin D (CD) deficiency are characterized by a progressive
      and relentless neurodegenerative phenotype similar to that observed in Neuronal
      Ceroid Lipofuscinoses (NCL), a group of pediatric neurodegenerative diseases
      known collectively as Batten Disease. We have shown recently that the targeted
      deletion of the pro-apoptotic molecule Bax prevents apoptotic markers but not
      neuron death and neurodegeneration induced by CD deficiency, which suggests that
      alterations in the macroautophagy-lysosomal degradation pathway can mediate
      neuron death in NCL/Batten Disease in the absence of apoptosis. Herein, we review
      CD deficiency in the broader context of NCL and offer potential mechanisms for
      neuron death and neurodegeneration induced by CD deficiency.

PMID- 17495519
TI  - Signal-dependent control of autophagy and cell death in colorectal cancer cell:
      the role of the p38 pathway.
AB  - Autophagy is a vacuolar process leading to the degradation of long-lived proteins
      and cytoplasmic organelles in eukaryotes. This process has an important role in
      normal and cancer cells during adaptation to changing environmental conditions,
      cellular and tissue remodeling, and cell death. To date, several signaling
      cascades have been described to regulate autophagy in a cell type-specific and
      signal-dependent manner. We found that pharmacological blockade of the p38
      pathway in colorectal cancer cells, either by the inhibitor SB202190 or by
      genetic ablation of p38 alpha kinase, causes cell cycle arrest and autophagic
      cell death. In these cells, a complex network of intracellular kinase cascades
      controls autophagy and survival since the effect of p38 alpha blockade is
      differentially affected by the pharmacological inhibition of MEK1, PI(3)K class I
      and III, and mTOR or by the differentiation status. Collectively, our results
      suggest an opportunity for exploiting the pharmacological manipulation of the p38
      alpha pathway in the treatment of colorectal cancer. Given the number of drugs,
      currently available or under development, that target the p38 pathway, it stands
      to reason that elucidating the molecular mechanisms that link p38 and autophagy
      might have an impact on the clinical translation of these drugs.

PMID- 17495521
TI  - Immune response to firefly luciferase as a naked DNA.
AB  - Firefly luciferase (Fluc) has been widely used as a reporter gene. The aim of
      this study was to investigate immune response to luciferase protein after an
      intradermal injection of pcDNA3.1-Fluc in immunocompetent BALB/c mice. We
      observed bioluminescence at injection sites from one to seven days post-injection
      when pcDNA3.1-Fluc was intradermally injected into ear-pinnae. To observe induced
      immune response, the percentages of CD8+IFNgamma+ cells in the draining lymphoid
      cells of immunocompetent BALB/c mice immunized by pcDNA3.1-Fluc were measured.
      And the tumor growths of CT26/Fluc in pcDNA3.1-Fluc group were monitored by
      observing bioluminescent signals and measuring tumor mass, and these were
      compared with those of the pcDNA3.1 group in immunocompetent BALB/c mice and
      immunodeficient Nu/Nu mice. In the immunocompetent BALB/c mice, percentages of
      CD8+IFNgamma+ cells in the pcDNA3.1-Fluc group were higher than those in the
      pcDNA3.1 group. Ten days after tumor inoculation, tumor growth inhibition was
      found in the pcDNA3.1-Fluc group, but not in the pcDNA3.1 group in the
      immunocompetent BALB/c mice. No significant difference in tumor growth inhibition
      was observed when CT26/Fluc was injected into immunodeficient Nu/Nu mice. In
      terms of cytokine profiles of draining lymphoid cells of immunized mice, IFNgamma
      protein levels in the pcDNA3.1-Fluc group were higher than in pcDNA3.1 group
      animals among the immunocompetent BALB/c mice. In conclusion, Fluc induced a Th1
      immune response to Fluc protein delivered by injecting pcDNA3.1-Fluc into
      immunocompetent BALB/c mice. We suggest that immune response to the Fluc gene is
      cautionary in preclinical or clinical trials involving the Fluc gene, and that
      the immunologic potential of firefly luciferase as a naked DNA may be useful in
      cancer immunotherapy.

PMID- 17495520
TI  - Epidermal growth factor receptor plays a significant role in hepatocyte growth
      factor mediated biological responses in mammary epithelial cells.
AB  - Breast cancers often have deregulated hepatocyte growth factor (HGF) and c-Met
      signaling that results in increased tumor growth and invasion. Elucidating the
      mechanism responsible for HGF/c-Met action in breast cancer progression has been
      difficult as c-Met communicates with a number of secondary receptors that can
      lead to various pathological outcomes. Understanding how these secondary
      receptors facilitate HGF/c-Met cellular responses will aid in the development of
      better therapeutic treatment options for breast cancer patients with elevated HGF
      signaling. In the present study it was shown that the epidermal growth factor
      receptor (EGFR) plays a significant role in HGF/c-Met mediated biological
      activities indicative of advanced tumor pathology, including enhanced
      proliferation and invasion. The clinically relevant EGFR inhibitor gefitinib was
      used to determine the role of EGFR in HGF-induced proliferation and motility in
      several mammary carcinoma cells including PyVmT, MDA-MB-231 and 4T1. Our analyses
      indicated that EGFR inhibition significantly blocked HGF activation of c-Met and
      EGFR and that inhibition of these pathways mitigated HGF induced proliferation
      and motility. The data indicate that this inhibition was not through a direct
      effect of gefitinib on c-Met, but that EGFR is necessary for c-Met activation in
      the assays performed. These results provide a novel mechanism of action for EGFR
      as a mediator of HGF signaling thereby linking EGFR to the oncogenic potential of
      c-Met in mammary carcinomas cells.

PMID- 17495522
TI  - Defibrotide: an endothelium protecting and stabilizing drug, has an anti
      angiogenic potential in vitro and in vivo.
AB  - Defibrotide (DF) is a polydisperse mixture of 90% single-stranded
      oligonucleotides with anti-thrombotic and anti-apoptotic functions. DF is used in
      the treatment of endothelial complications in the course of allogeneic stem cell
      transplantation. Recent preclinical evidence suggests that DF might also have
      anti-neoplastic properties. In the present study we hypothesized that DF might
      inhibit tumors via an anti-angiogenic effect. The anti-angiogenic potential of DF
      was tested in vitro using human microvascular endothelial cells forming vessel
      structures across a layer of dermal fibroblasts. Our results show that
      pharmacologic DF concentrations (100 mug/ml) significantly reduced vessel
      formation in this assay. Similarly, DF blocked sprouting from cultured rat aortic
      rings. In vivo, angiogenesis in a human gastric tumor (TMK1) implanted in dorsal
      skin-fold chambers (in nude mice) was inhibited by i.v. application of 450 mg/kg
      DF. Notably, due to its short half-life, DF was most effective when given on a
      daily basis. Although the precise mechanism of DF remains to be elucidated,
      initial Western blots show that DF reduces phosphorylation-activation of p70S6
      kinase, which is a key target in the PI3K/Akt/mTOR signaling pathway linked to
      endothelial cell and pericyte proliferation and activation. However, in vitro
      data suggest that DF acts independently of vascular endothelial growth factor.
      Taken together, our data suggest that while DF is known for its endothelium
      protecting function in SCT, it also inhibits formation of new blood vessels, and
      thus should be considered for further testing as an adjuvant anti-cancer agent,
      either alone, or in combination with other drugs.

PMID- 17495523
TI  - Allele-dependent variation in the relative cellular potency of distinct EGFR
      inhibitors.
AB  - Targeted cancer therapies impede cancer cell growth by inhibiting the function of
      activated oncogene products. Patients with non-small cell lung cancer and somatic
      mutations of EGFR can have a dramatic response to treatment with erlotinib and
      gefitinib; different somatic mutations are associated with different times to
      progression and survival. In this study, the relative and absolute potencies of
      two distinct EGFR tyrosine kinase inhibitors, erlotinib and an investigational
      irreversible inhibitor, HKI-272, were found to vary significantly in a panel of
      Ba/F3 cells transformed by representative EGFR somatic mutations. HKI-272 more
      potently inhibited the primary exon 20 insertion mutants, the secondary erlotinib
      resistance mutants including T790M and many erlotinib-sensitive mutants including
      L858R. In contrast, erlotinib is a more potent inhibitor of the major exon 19
      deletion mutants than is HKI-272. Analyses of EGFR autophosphorylation patterns
      confirmed the mutation-specific variation in relative potency of these tyrosine
      kinase inhibitors. Our finding that distinct EGFR inhibitors are more effective
      in vitro for different mutant forms of the protein suggests that tyrosine kinase
      inhibitor treatment could be tailored to specific EGFR mutations. More broadly,
      these results imply that the development and deployment of targeted therapies
      should focus on inhibition of specific cancer-causing mutations, not only on the
      mutated target.

PMID- 17495524
TI  - Interim analysis of toxicity and response in phase 1 trial of systemic targeted
      alpha therapy for metastatic melanoma.
AB  - PURPOSE: The aim is to assess toxicity and response of systemic alpha therapy for
      metastatic melanoma. EXPERIMENTAL DESIGN: This is an open-labelled Phase 1 dose
      escalation study to establish the effective dose of the alpha-immunoconjugate
      (213)Bi-cDTPA-9.2.27 mAb (AIC). Tools used to investigate the effects were
      physical examination; imaging of tumors; pathology; GFR; CT and changes in tumor
      marker. Responses were assessed using RECIST criteria. RESULTS AND DISCUSSION:
      Twenty-two patients with stage IV melanoma/in-transit metastasis were treated
      with activities of 55-947 MBq. Using RECIST criteria 50% showed stable disease
      and 14% showed partial response. One patient (6%) showed near complete response
      and was retreated because of an excellent response to the initial treatment.
      Another patient showed response in his tumor on mandible and reduction in lung
      lesions. Overall 30% showed progressive disease. The tumor marker melanoma
      inhibitory activity protein (MIA) showed reductions over eight weeks in most of
      the patients. The disparity of dose with responders is discussed. No toxicity was
      observed over the range of administered activities. CONCLUSION: Observation of
      responses without any toxicity indicates that targeted alpha therapy has the
      potential to be a safe and effective therapeutic approach for metastatic
      melanoma.

PMID- 17495525
TI  - The expression level of the tumor suppressor retinoblastoma protein (Rb)
      influences the antileukemic efficacy of erucylphospho-N,N,N
      trimethylpropylammonium (ErPC3).
AB  - The alkylphosphocholine erucylphospho-N,N,N-trimethylpropylammonium (ErPC3) is a
      promising new drug for treating various types of cancer. Its mechanism of action
      is not yet fully understood but is related to the Rb tumor suppressor protein. In
      the present study, we investigated the role of decreased Rb expression levels for
      the antileukemic efficacy of ErPC3 in BV-173 and K-562 CML-derived cell lines. We
      used antisense technique to knock down Rb levels in the two cell lines in
      addition to ErPC3 treatment. Cells with reduced Rb expression showed a diminished
      sensitivity to ErPC3 exposure, as determined by MTT (BV-173 and K-562) and
      clonogenicity assays (K-562 only), if concentrations below the IC50 were used.
      The feasibility of Rb knockdown varied between BV-173 and K-562 cells, with the
      former being distinctly more sensitive than the latter. We conclude that
      sufficient Rb levels are important for the cytotoxic and anticlonogenic effects
      of ErPC3 at levels below the IC(50), but that higher concentrations of ErPC3 are
      less dependent on Rb status.

PMID- 17495526
TI  - Cell cycle regulation targets of MYCN identified by gene expression microarrays.
AB  - BACKGROUND: We have previously shown that MYCN knockdown causes a G1 arrest in
      MYCN amplified (MNA), p53 wild type (wt) and p53 mutant MNA neuroblastoma cell
      lines, with increases in p21(WAF1) and hypo RB in p53 wt cell lines. HYPOTHESIS:
      MYCN acts by inhibiting p21(WAF1), and also by p21(WAF1) independent mechanisms
      to override the G1 checkpoint in exponentially growing cells. METHODS: Genes
      potentially regulated by MYCN were identified using gene expression microarrays
      in p53 wt MNA IMR-32 and p53 mutant MNA SKNBE(2c) neuroblastoma cell lines
      treated with MYCN or scrambled siRNA. Results were validated using qRT-PCR and
      confirmed using the regulatable MYCN expression system (SHEP Tet21N). RESULTS:
      MYCN knockdown altered the expression of several cell cycle related genes. SKP2
      was down regulated in both cell lines, and up regulated in MYCN+ Tet21N cells.
      Expression of the WNT antagonist DKK3 increased in both cell lines and decreased
      in MYCN+ Tet21N cells. Expression of CDKN1C (p57(cip2)) and TP53INP1 also
      increased after MYCN knockdown. CONCLUSIONS: MYCN may override the G1 checkpoint
      through down-regulation of SKP2 and TP53INP1 resulting in reduced p21(WAF1)
      expression in p53 wt cell lines, and in addition may act through the WNT
      signaling pathway in a p53 independent manner.

PMID- 17495527
TI  - Localized treatment with a novel FDA-approved proteasome inhibitor blocks the
      degradation of dystrophin and dystrophin-associated proteins in mdx mice.
AB  - Duchenne Muscular Dystrophy (DMD) is an incurable inherited disease of childhood,
      characterized by progressive muscle degeneration and weakness. Our previous
      findings supported the idea that dystrophin and associated proteins, absent or
      greatly reduced in DMD, are degraded in dystrophin-deficient muscle by the
      proteasomal-dependent pathway. Indeed, treatment with the proteasome inhibitor MG
      132 of skeletal muscles from mdx mice--a spontaneous mouse model of DMD--as well
      as from DMD patients, effectively rescued the expression and correct cellular
      localization of dystrophin and associated proteins. These promising results led
      us to further explore the use of proteasome inhibitors as a therapy for DMD.
      Therefore, we directed our attention towards two new dipeptide boronic acid
      inhibitors blocking the proteasomal-dependent degradation pathway: Velcade
      (bortezomib or PS-341) and MLN273 (PS-273). The exciting aspect of this
      development is that these drugs have already progressed to preclinical and
      clinical trials, in different fields than muscular dystrophy. Indeed, Velcade has
      been already FDA-approved for treatment of multiple myeloma and its side effects
      had been already explored and managed. Promisingly, MLN273 is currently in the
      preclinical trial phase. Here, we test the effectiveness of Velcade and MLN273 by
      local injection into the gastrocnemius muscle of mdx mice. We show the rescue of
      expression and membrane localization of alpha-dystroglycan, beta-dystroglycan,
      alpha-sarcoglycan, and dystrophin after Velcade and MLN273 localized treatment,
      versus untreated (PBS only) mdx mice. Intriguingly, we also show that localized
      treatment with Velcade and MLN273 reduces the activation of Nuclear Factor-kappaB
      (NFkB). Because the NFkB pathway has been shown to be involved in inflammation
      responses in myopathies and DMD, our current results may have important clinical
      implications. Clearly, more investigations are needed, but our results emphasize
      the effectiveness of the pharmacological approach as a potential treatment for
      Duchenne muscular dystrophy.

PMID- 17495528
TI  - The DEAD-box p68/p72 proteins and the noncoding RNA steroid receptor activator
      SRA: eclectic regulators of disparate biological functions.
AB  - p68 and p72 are RNA-binding proteins endowed with RNA helicase and RNA-protein
      complex remodeling activities. One of the RNAs associated with p68/p72 is the
      noncoding Steroid Receptors RNA Activator (SRA). Here we review recent findings
      on the cellular processes regulated by either p68/p72 alone or in combination
      with SRA and discuss the transcriptional events influenced by these molecules.

PMID- 17495529
TI  - The spindle midzone microtubule-associated proteins Ase1p and Cin8p affect the
      number and orientation of astral microtubules in Saccharomyces cerevisiae.
AB  - The nucleus of the budding yeast S. cerevisiae has to move to the bud neck during
      mitosis in order for proper DNA segregation to take place. This movement is
      mediated by spindle and astral microtubules, and it relies on forces generated by
      microtubule-associated motor proteins. When budding yeast cells express the non
      cleavable cohesin subunit, Scc1-RRDD, sister chromatid separation is blocked,
      preventing the spindle from elongating. Thus, in the presence of Scc1-RRDD
      nuclear positioning is mediated solely by forces acting through astral
      microtubules. We have previously shown that under these conditions cells exit
      mitosis with the nucleus in the mother cells, and that the position of the
      nucleus is determined, at least in part, by the FEAR pathway, which regulates
      various aspects of mitotic exit. When the FEAR pathway is inactivated, cells
      expressing Scc1-RRDD exit mitosis with the nucleus in the daughter cells
      (referred to as a "daughterly phenotype"). In order to find additional proteins
      that participate in nuclear positioning, we screened a series of mutant strains
      for those that displayed a daughterly phenotype when Scc1-RRDD was expressed. The
      most prominent defects were seen in ase1delta and cin8delta mutant cells. Both
      Ase1p and Cin8p were previously shown to be nuclear and to be involved in spindle
      function. We show here that deletion of ASE1 or CIN8 causes a defect in SPB
      separation and leads to an abnormal number of astral microtubules and a change in
      their orientation within the cell. Taken together, these results suggest that in
      budding yeast Ase1p and Cin8p affect nuclear positioning through astral micro
      tubule-dependent mechanisms.

PMID- 17495530
TI  - Signal transduction in human embryo implantation.
AB  - Determining the molecular mechanism of human embryo implantation is an extremely
      challenging task due to the limitation of materials and significant differences
      in this process among mammalian species. Trophinin has been identified as an
      apical cell adhesion molecule with potential involvement in human embryo
      implantation. We found that trophinin-mediated cell adhesion triggers signal
      transduction in human trophoblastic cells for proliferation and invasion,
      implicating in trophectoderm cell activation for placental formation. Prior to
      cell adhesion trophinin arrests ErbB4 by binding through bystin, which prevents
      ErbB4 from activation. Trophinin-mediated cell adhesion causes dissociation of
      bystin from trophinin, freeing ErbB4 from arrest and enabling tyrosine
      phosphorylation. Therefore trophinin functions as an adhesion molecule on the
      cell surface and as a molecular switch for trophoblast activation in the
      cytoplasm.

PMID- 17495531
TI  - Cyclin B and cyclin A confer different substrate recognition properties on CDK2.
AB  - The transitions of the cell cycle are regulated by the cyclin dependent protein
      kinases (CDKs). The cyclins activate their respective CDKs and confer substrate
      recognition properties. We report the structure of phospho-CDK2/cyclin B and show
      that cyclin B confers M phase-like properties on CDK2, the kinase that is usually
      associated with S phase. Cyclin B produces an almost identical activated
      conformation of CDK2 as that produced by cyclin A. There are differences between
      cyclin A and cyclin B at the recruitment site, which in cyclin A is used to
      recruit substrates containing an RXL motif. Because of sequence differences this
      site in cyclin B binds RXL motifs more weakly than in cyclin A. Despite
      similarity in kinase structures, phospho-CDK2/cyclin B phosphorylates substrates,
      such as nuclear lamin and a model peptide derived from p107, at sequences SPXX
      that differ from the canonical CDK2/cyclin A substrate recognition motif, SPXK.
      CDK2/cyclin B phosphorylation at these non-canonical sites is not dependent on
      the presence of a RXL recruitment motif. The p107 peptide contains two SP motifs
      each followed by a non-canonical sequence of which only one site (Ser640) is
      phosphorylated by pCDK2/cyclin A while two sites are phosphorylated by
      pCDK2/cyclin B. The second site is too close to the RXL motif to allow the cyclin
      A recruitment site to be effective, as previous work has shown that there must be
      at least 16 residues between the catalytic site serine and the RXL motif. Thus
      the cyclins A and B in addition to their role in promoting the activatory
      conformational switch in CDK2, also provide differential substrate specificity.

PMID- 17495532
TI  - Terminal myeloid differentiation is uncoupled from cell cycle arrest.
AB  - It has been assumed that terminal myeloid differentiation and cell cycle arrest
      are coupled processes, and that prohibiting cell cycle arrest would block
      differentiation. Previously we have shown that, using the murine M1 myeloid
      leukemic cell line, deregulated expression of the proto-oncogene c-myc results in
      cells that cannot be induced to undergo terminal differentiation and continued to
      proliferate. It has also been shown that ectopic expression of Egr-1 abrogated
      the c-Myc block in terminal myeloid differentiation, yet there was no
      accumulation of cells in the G0/G1 phase of the cell cycle. In this study we
      conclusively demonstrate that M1Myc/Egr-1 cells terminally differentiate while
      still actively cycling and synthesizing DNA, concluding that the terminal myeloid
      differentiation program is uncoupled from growth arrest. How deregulated
      expression/activation of proto-oncogenes that promote cell cycle progression
      interferes with differentiation and how differentiation is regulated
      independently of cell cycle control are discussed, as well as the implications
      with regard to differentiation therapy.

PMID- 17495533
TI  - The crystal structure of human cyclin B.
AB  - Cyclin B is the key regulatory protein controlling mitosis in all eukaryotes,
      where it binds cyclin-dependent kinase, cdk1, forming a complex which initiates
      the mitotic program through phosphorylation of select proteins. Cyclin B
      regulates the activation, subcellular localization, and substrate specificity of
      cdk1, and destruction of cyclin B is necessary for mitotic exit. Overexpression
      of human cyclin B1 has been found in numerous cancers and has been associated
      with tumor aggressiveness. Here we report the crystal structure of human cyclin
      B1 to 2.9 A. Comparison of the structure with cyclin A and cyclin E reveals
      remarkably similar N-terminal cyclin box motifs but significant differences among
      the C-terminal cyclin box lobes. Divergence in sequence gives rise to unique
      interaction surfaces at the proposed cyclin B/cdk1 interface as well as the 'RxL'
      motif substrate binding site on cyclin B. Examination of the structure provides
      insight into the molecular basis for differential affinities of protein based
      cyclin/cdk inhibitors such as p27, substrate recognition, and cdk interaction.

PMID- 17495534
TI  - Identification of a missing sequence and functionally important residues of 16S
      rRNA:m(1)A1408 methyltransferase KamB that causes bacterial resistance to
      aminoglycoside antibiotics.

PMID- 17495535
TI  - Chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine, is a specific
      activator of oncogenic Ras.
AB  - N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a well-known chemical carcinogen
      that is widely used for animal carcinogenesis model. Treatment of MNNG, through
      drinking-water, can evoke multiple tumors in gastro-intestinal tract. In
      addition, MNNG shows the synergic effect with infection such as H. pylori on
      gastric cancer formation. Although tumorigenic ability of MNNG is known to be
      related with DNA alkylation, however, recent reports suggested that MNNG-induced
      tumors do not show the difference in DNA methylation, and genetic mutation
      profile is quite different from similar DNA alkylating agent, MNU-inducing
      cancer. Otherwise, genetic mutation of Ras is frequently detected in MNNG-induced
      tumors. Considering them, tumorigenic property of MNNG would be related with Ras.
      So we checked the effect of MNNG on Ras pathway. In this study, we demonstrated
      that MNNG could activate Ras-MAPK pathway as oncogenic Ras dependent manner.
      Activation of Erk by MNNG could not suppressed by cycloheximide and ALLN. In
      addition, Inhibition of PI3K, p38/HOG1, Raf, and CDK could not block the MNNG
      induced p-Erk activation, whereas U0126 and PD98059 abolished it. Moreover, MNNG
      could reduce the expression of E-cadherin and promote dissociation of beta
      catenin from E-cadherin through oncogenic-Ras-MAPK pathway. These results
      strongly suggested that oncogenic Ras would be direct target of MNNG and provided
      new insight that carcinogen also possesses it specific target.

PMID- 17495536
TI  - Clamping the Mec1/ATR checkpoint kinase into action.
AB  - The yeast checkpoint protein kinase Mec1, the ortholog of human ATR, is the
      essential upstream regulator of the cell cycle checkpoint in response to DNA
      damage and to stalling of DNA replication forks. The activity of Mec1/ATR is not
      directly regulated by the DNA substrates that signal checkpoint activation.
      Rather the signal appears to be transduced to Mec1 by factors that interact with
      the signaling DNA substrates. One of these factors, the DNA damage checkpoint
      clamp Rad17-Mec3-Ddc1 (human 9-1-1) is loaded onto gapped DNA resulting from the
      partial repair of DNA damage, and the Ddc1 subunit of this complex activates
      Mec1. In vertebrate cells, the TopBP1 protein (Cut5 in S. pombe and Dpb11 in S.
      cervisiae) that is also required for establishment of the replication fork,
      functions during replication fork dysfunction to activate ATR. Both mechanisms of
      activation generally upregulate the kinase activity towards all downstream
      targets.

PMID- 17495537
TI  - Order in the classroom: graded responses to instructive Hh signaling in the CNS.
AB  - In many animals, the secreted Hedgehog (Hh) signaling proteins play important
      roles during development and in adults. Studies in both flies and vertebrates
      indicate that Hh functions as a morphogen to elicit different responses at
      distinct concentration thresholds. In vertebrates, Gli proteins are the primary
      transcriptional mediators of Hh target genes. However, the mechanisms that
      implement specific genetic responses to graded Hh-Gli signaling are only just
      beginning to be understood. In particular, it is unclear whether target gene
      responses are determined solely by the ambient levels of pathway activity, or if
      other pathways or factors function to amplify or attenuate the response to this
      signal to provide an additional level of context that permits a more fine-tuned
      outcome. Here, I will review recent evidence suggesting that the response of some
      Hh-Gli target genes in the CNS is regulated by the activity of another important
      extracellular signal, the canonical Wnt pathway. The possibility that the Hh and
      Wnt pathways interact at the transcriptional level has broad significance for
      understanding normal embryogenesis and diagnosing and treating the numerous
      developmental disorders and cancers that involve these two pathways. Thus, while
      Hh-Gli signals provide important information, it is likely that they receive
      assistance from other "instructors".

PMID- 17495538
TI  - Integrating biomedical knowledge to model pathways of prostate cancer
      progression.
AB  - Due to pathologic, histologic, and biologic variation within prostate cancers,
      profiling the genetic changes associated with disease progression has been
      difficult. Although initial integration of data from profiling studies had been
      limited by platform variation, bioinformatic tools and analytic techniques have
      enabled integrative analysis of profiling studies and the identification of more
      robust and valid profiles. The identification of key transition points in the
      progression of prostate cancer relies on profiling precursor lesions and "pure"
      cell populations. Utilizing laser-capture microdissection to isolate 101 cell
      populations, a more specific genetic profile of progression from benign
      epithelium to metastatic disease was obtained. This laser-capture profile was
      analyzed in the context of the molecular concepts map (MCM), a compendium of over
      20,000 molecular concepts including other expression profiles of prostate cancer,
      to obtain an integrative molecular model of progression. The conceptual
      connections associated with progression confirm that prostate cancer biology is
      largely driven by pathways related to androgen signaling and epithelial cell
      biology; however, further analysis of concepts associated with progression
      suggests stromal factors are highly associated with progression of prostate
      cancer. The effect of stromal signatures on the progression model suggests the
      impact of stromal signature downregulation may reflect both a change in the
      epithelia:stroma ratio within higher grade tumors and also a microenvironment
      influence on prostate epithelia. Analyzing complex gene expression signatures in
      the context of molecular concepts improves integrative models and may improve
      detection, prognostication, or targeted therapy.

PMID- 17495539
TI  - Chk1 is required for G2/M checkpoint response induced by the catalytic
      topoisomerase II inhibitor ICRF-193.

PMID- 17495540
TI  - Myocardin in tumor suppression and myofibroblast differentiation.
AB  - The malignant transformation process is associated with defects in cell cycle
      regulation and disruption of the normal differentiation programs in both
      neoplastic and adjacent stroma cells. However, the relationships between the cell
      cycle, differentiation and cancer are very complex and tissue specific. Recently
      we have demonstrated a previously unrecognized role in human carcinogenesis for
      the important regulator of cardiac and smooth muscle differentiation, myocardin.
      Myocardin expression is frequently repressed during human malignant
      transformation contributing to a differentiation defect in the premalignant
      mesenchymal cells. TGFbeta treatment, serum deprivation and intact contact
      inhibition response all contribute to myocardin induction and differentiation.
      Positive regulation of myocardin mRNA levels and activity by the p16/Rb pathway
      provides a molecular link between cell cycle and differentiation defects during
      cancer development. In addition, we show that myocardin represses its own
      expression in human fibroblasts. This negative autoregulatory loop might be
      potentially important for restraining myocardin activity and allowing
      reversibility of fibroblast-myofibroblast phenotypic conversion. Here we discuss
      the emerging role of myocardin in tumor suppression as well as novel aspects of
      its regulation in normal and malignant conditions.

PMID- 17495541
TI  - Genetic screen for chromosome instability in mice: Mcm4 and breast cancer.
AB  - We recently isolated a hypomorphic mutation of Mcm4 in a phenotype-based screen
      for chromosome instability in mice. This mutation, named Chaos3 (chromosome
      aberrations occurring spontaneously 3), causes exclusively mammary
      adenocarcinomas in approximately 80% of homozygous females. Mcm4 encodes a
      subunit of the MCM2-7 complex, the replication-licensing factor and the
      replicative helicase. The Mcm4(Chaos3) mutation appears to destabilize the MCM2-7
      complex, causing impaired DNA replication. These findings demonstrate, for the
      first time, the causative role of an Mcm mutation in cancer development.
      Furthermore, this raises the possibility that hypomorphic mutations in MCM2-7
      genes may increase breast cancer risk in humans.

PMID- 17495542
TI  - Coordinated regulation of growth genes in Saccharomyces cerevisiae.
AB  - It is imperative that quiescent Saccharomyces cerevisiae cells respond rapidly to
      fresh medium: the cell that initiates growth and division soonest has the most
      progeny. Several laboratories have used DNA microarrays to identify transcripts
      that are altered when fresh medium is added to quiescent cells. We combined
      published data with our own to address several questions: Do these experiments
      taken together identify a core set of genes that is reproducibly affected when
      quiescent cells are stimulated by nutrient repletion? Is this gene set
      coregulated in response to other environmental challenges? Does promoter histone
      occupancy correlate with the mRNA data? Despite diverse experimental designs, the
      data were highly correlated, generating a set of nutrient repletion transcripts.
      Glucose addition accounted for the response. These transcripts were also
      coregulated in response to diverse stresses. Promoters were associated with
      increased histone acetylation and decreased histone occupancy when induced, and
      high histone occupancy with low acetylation when repressed. The presence of RRPE
      and PAC promoter elements correlated with nutrient responsiveness and a dynamic
      pattern of histone occupancy and acetylation. Correlative evidence supports the
      idea that some mRNAs may be upregulated by release from sequestration in RNA
      protein complexes.

PMID- 17495543
TI  - Protein synthesis and aging: eIF4E and the soma vs. germline distinction.
AB  - Classic studies in diverse organisms, including humans, have demonstrated that
      aging is accompanied by marked alterations in both general and specific protein
      synthesis. These early observations established a link between the aging process
      and the regulation of protein synthesis. However, two important questions
      remained. First, what are the molecular mechanisms underlying the changes in
      protein synthesis during aging? Second, are these changes simply a consequence of
      aging or do they actually have a causative role in senescent decline? We have
      recently shown that elimination of a specific isoform of the eukaryotic mRNA
      translation initiation factor 4E (eIF4E) that functions in somatic cells, reduces
      protein synthesis and extends lifespan in the nematode Caenorhabditis elegans.
      Depletion of eIF4E in the soma extends lifespan via a mechanism independent of
      the insulin/IGF pathway that modulates aging in diverse species. Our findings
      suggest that regulation of protein synthesis is an important determinant of
      longevity and provide a framework for elucidating the mechanisms by which the
      rate of protein synthesis influences the process of aging.

PMID- 17495544
TI  - The cell division cycle puts up with unprotected telomeres: cell cycle regulated
      telomere uncapping as a means to achieve telomere homeostasis.
AB  - Telomeres have unique properties that distinguish natural chromosomal ends from
      accidental DNA double-strand interruptions arising elsewhere in the genome.
      However, the slightest perturbation in their unique organization may obliterate
      this distinction, channelling chromosomal ends into unwarranted repair events,
      eventually causing genome instability. Recent results revealed that the
      processing of both dysfunctional telomeres and accidental DNA double strand
      breaks (DSB) by DNA repair activities is tightly regulated in a cell cycle
      dependent manner by the S phase-promoting cell cycle kinase CDK1 (Clb-Cdc28p).
      Surprisingly, the cell cycle determinants and the timing of processing at
      unprotected telomeres closely match the requirements of other transactions that
      occur at telomeres. In particular, the replenishment of telomeric repeats by
      telomerase is tightly linked to cell cycle progression and occurs in the same
      interval. Furthermore, cell survival in the absence of essential telomeric
      proteins being dependent on telomere-telomere recombination mechanisms may
      require a similar regulation. Thus, a temporally limited state of telomere
      dysfunction leading to chromosome end processing may represent a well-governed
      cell cycle event that constitutes an integral part of the assembly of a new
      functional telomere.

PMID- 17495546
TI  - The value of professional certification for clinical nurse specialists.

PMID- 17495547
TI  - Computerized provider order entry and prescribing and the evidence for safe
      practice: update for the clinical nurse specialist.

PMID- 17495548
TI  - The entrepreneur and the business plan.

PMID- 17495549
TI  - Tool development for evaluation of clinical nurse specialist competencies in
      graduate students: a pilot study.
AB  - PURPOSE: The purpose of this study was psychometric testing of the tool, Self
      Evaluation of CNS Competency Development. METHODS: The tool was developed using
      the NACNS competencies, with some concepts added to reflect graduate program
      objectives. The student sample was 33 students who provided informed consent and
      completed the tool. The preceptor sample was 6 preceptors who clinically
      supervised 6 students. RESULTS: As expected, independent samples t tests with
      matched pairs of 6 students and preceptors showed that there were no mean
      differences in 9 of the 12 categories within the 3 spheres of influence. Using
      the contrasted groups approach, discriminant function analysis showed that 91.7%
      of beginning and ending students were correctly classified. Cronbach alpha was
      estimated as .96. CONCLUSION: Results show partial support for criterion-related
      validity and construct validity. Tool reliability is satisfactory. Further
      testing with larger samples of students and clinical nurse specialists is
      recommended.

PMID- 17495550
TI  - Seeking control through the determination of diet: a qualitative investigation of
      women with irritable bowel syndrome and inflammatory bowel disease.
AB  - PURPOSE: The overall objective of this investigation was to study the lived
      experience, in relation to diet, of women who have been diagnosed with
      Inflammatory Bowel Disease and/or Irritable Bowel Syndrome. This study
      specifically explored pre-illness and postdiagnosis dietary patterns of
      participants with an emphasis on the changes, if any, that participants had made
      to their diet. METHODS: This study took place on a university campus in
      southwestern Ontario, Canada. Eight women between the ages of 18 and 23 years
      were recruited. Participants completed a consent form, background questionnaire,
      and a 14-day food diary. Participant also engaged in one-on-one semistructured
      interviews that consisted of 8 open-ended questions aimed at gaining a thorough
      understanding of the lived experience of these women, with respect to their
      dietary practices. RESULTS: The 3 major themes identified included: control;
      family and friend support; and adverse behaviors. The salient theme of control
      included the subthemes timing and awareness of surroundings, giving into
      temptations, and determination of diet. Determining one's diet, the subtheme that
      is addressed in this article, involved several key elements, including (1) the
      role of the physician(s), (2) experimentation, (3) seeking information, and (4)
      food modifications. CONCLUSIONS: Diet was the primary behavioral factor
      manipulated by participants to manage their conditions. The determination of
      potential trigger foods/beverages, however, entailed an often frustrating process
      of trial and error, in which few of the women received assistance from primary
      healthcare professionals. As a result, many of the women sought dietary
      information from alternate sources, some of which may not provide reliable
      information. Through experimentation and, for some, the documentation of food
      intake and symptom production, all participants identified food/beverage items
      they believed to cause symptom development. Although similar items were
      identified by many, all participants had individual triggers and sensitivities.

PMID- 17495551
TI  - Massage therapy: a comfort intervention for cardiac surgery patients.
AB  - Integrative therapies have gained support in the literature as a method to
      control pain and anxiety. Many institutions have integrated massage therapy into
      their programs. Few studies have looked at the specific benefits of massage
      therapy for cardiac surgical patients. These patients undergo long surgical
      procedures and often complain of back, shoulder, and neck pain or general stress
      and tension. Clinical nurse specialist identify the benefits for patients and
      bring the evidence on massage therapy to the clinical setting. This article will
      provide an overview of the benefits of massage in the reduction of pain, anxiety,
      and tension in cardiac surgical patients. Reports of benefits seen with
      integration of massage in 1 cardiac surgical unit as part of evidence-based
      practice initiative for management of pain will be described. A clinical case
      example of a patient who has experienced cardiac surgery and received massage
      therapy will be shared.

PMID- 17495553
TI  - Clinical nurse specialist profile: Mary Fran Tracy. Interview by Jo Ellen Rust.

PMID- 17495554
TI  - The inspiring and regenerative power of the arts.

PMID- 17495556
TI  - Post-traumatic stress disorder at the end of life.

PMID- 17495557
TI  - Wounded warriors: their last battle.

PMID- 17495560
TI  - The AD-LIFE trial: working to integrate medical and psychosocial care management
      models.
AB  - Interdisciplinary care management that fully integrates medical and social care
      is advocated for optimal care of patients with many types of chronic illnesses,
      yet the effectiveness of this care model has been insufficiently tested using
      randomized controlled trials. This article presents the results of a pilot care
      management program and a description of a larger randomized controlled trial
      modeled after the pilot program (the After Discharge Care Management of Low
      Income Frail Elderly [AD-LIFE] trial). It compares an integrated medical and
      social care management model (intervention group) with a purely social model
      (control group) involving low-income elderly patients with chronic conditions and
      functional impairment at high risk for rehospitalization or nursing home
      placement. A case study of a patient participant in the AD-LIFE study is
      presented. The case illustrates the positive effects of the intervention on
      biopsychosocial outcomes.

PMID- 17495561
TI  - Home-based primary care: the care of the veteran at home.
AB  - Home-Based Primary Care is a program designed by the Department of Veteran
      Affairs (VA) to care for frail, medically complex, elderly veteran patients in
      their home setting. Unique to the VA, the program has similarities and
      differences in relation to typical Medicare/Medicaid home health and hospice
      programs. The VA has demonstrated success in maintaining the patients'
      independence and quality of life as well as exceptional management of chronic
      disease and prevention.

PMID- 17495562
TI  - Use of the electronic record in the home-based primary care programs of the
      Department of Veterans Affairs Health Care System.
AB  - Use of the electronic record in the Home-Based Primary Care (HBPC) programs of
      the Department of Veterans Affairs (VA) Health Care System is described. The VA
      electronic record is a complete computerized system for a patient's record. The
      use of this system provides instant information on the health status of each
      patient referred to and managed by home care.

PMID- 17495563
TI  - Evolution of evidence-based guidelines for home care: Wisconsin's experience.
AB  - In a pay-for-performance home health system, achieving superior patient outcomes
      becomes the key to agency success. Evidence-based guidelines help in the
      achievement of exceptional patient outcomes. In this article, the Wisconsin
      Homecare Organization (WHO) describes its journey toward basing its home health
      practice on evidence-based guidelines.

PMID- 17495564
TI  - Veterans' healthcare concerns: hepatitis C.

PMID- 17495566
TI  - Acute care hospitalization reduction efforts make us believers.

PMID- 17495567
TI  - What might the 110th Congress have in store for home health and hospice care in
      2007-2008?

PMID- 17495568
TI  - The other side of the door.

PMID- 17495569
TI  - Lost in time: the person in nursing research.

PMID- 17495570
TI  - Structural model for osteoporosis preventing behavior in postmenopausal women.
AB  - BACKGROUND: Osteoporosis prevention behaviors (OPBs) can prevent and delay bone
      deterioration; dual-energy X-ray absorptiometry (DXA) scan can identify
      osteoporosis and provide personal osteoporosis risk information that may promote
      prevention behaviors. OBJECTIVES: This study was designed to estimate
      relationships between receiving personal knowledge of bone mineral density
      (gained through DXA scan), general knowledge of osteoporosis, health beliefs, and
      the two OPBs of calcium intake and weight-bearing exercise in healthy
      postmenopausal women 50 to 65 years. METHODS: In this longitudinal, randomized
      clinical trial (including covariates), receipt of personal DXA information was
      manipulated by random assignment to the experimental or control group. The
      remaining antecedent and outcome variable measures were collected by
      questionnaire at three time points (initial [T1; pre-DXA], 6 months [T2], 12
      months [T3]) and by bone density assessment from 203 women over an 18-month
      period in 2001-2003. RESULTS: The experimental manipulation (DXA results) had a
      direct positive effect (beta = .23, p < .05) on calcium intake at T2, and
      indirectly at T3 through T2. Women in the experimental group who were informed
      they had osteopenia or osteoporosis had a greater T1-T2 change in daily calcium
      intake than those with normal bone density (beta = .23, p < .05). However,
      providing DXA results did not relate to change in exercise. Health beliefs and
      general osteoporosis knowledge predicted initial calcium and exercise levels;
      there was tentative evidence that susceptibility beliefs partially mediate
      between DXA results and change in calcium intake. DISCUSSION: Personal knowledge
      of DXA results was related significantly to increases in calcium intake in
      postmenopausal women, but not to exercise. Directions for further study are
      discussed.

PMID- 17495571
TI  - Understanding and measuring patients' assessment of the quality of nursing care.
AB  - BACKGROUND: Traditionally, patients have been considered incapable of evaluating
      the quality of care they receive, leading to their minimal involvement.
      OBJECTIVE: To develop the Patient's Assessment of Quality Scale--Acute Care
      Version (PAQS-ACV) to provide a mechanism through which patients can evaluate
      meaningfully the nursing care they receive. METHODS: Developed from qualitative
      interviews with patients, the original 90-item PAQS-ACV was tested with 1,470
      medical surgical patients in 43 units across seven hospitals. The typical patient
      was a married, 50-year-old, high school-educated patient hospitalized for the
      fourth time. Every 10th patient was asked to complete the PAQS-ACV 2 weeks later.
      RESULTS: After exploratory factor analysis, 45 items remained in five factors,
      accounting for 54% of the variance. Internal consistency estimates were above.83
      for four of the five factors, with the fifth factor being.68. Test-retest
      reliability ranged from .58 to .71. Content validity was established and
      construct validity has been explored preliminarily by examining the relationship
      between the PAQS-ACV scores and patients' compliance. DISCUSSION: Although the
      PAQS-ACV is a relatively new measure of quality nursing care, it has met many
      criteria for an adequate measure of quality care. The instrument fills a void in
      the assessment of quality by including patients in the direct evaluation of the
      care received.

PMID- 17495572
TI  - The impact of the parental illness representation on disease management in
      childhood asthma.
AB  - BACKGROUND: Despite significant advances in treatment modalities, morbidity due
      to childhood asthma has continued to increase, particularly for poor and minority
      children. OBJECTIVES: To describe the parental illness representation of asthma
      in juxtaposition to the professional model of asthma and to evaluate the impact
      of that illness representation on the adequacy of the child's medication regimen.
      METHODS: Parents (n = 228) of children with asthma were interviewed regarding
      illness beliefs using a semistructured interview. The impact of background
      characteristics, parental beliefs, the child's symptom interpretation, and the
      parent-healthcare provider (HCP) relationship on the adequacy of the child's
      medication regimen were evaluated. RESULTS: The parental and professional models
      of asthma differ markedly. Demographic risk factors (p = .005), low parental
      education (p < .0001), inaccurate symptom evaluation by the child (p = .02), and
      a poor parent-HCP relationship (p < .0001) had a negative effect on the parental
      illness representation. A parental illness representation concordant with the
      professional model of asthma (p = .05) and more formal asthma education (p = .02)
      had a direct positive effect on the medication regimen. Demographic risk factors
      (p = .006) and informal advice-seeking (p = .0003) had a negative impact on the
      regimen. The parental illness representation mediated the impact of demographic
      risk factors (p = .10), parental education (p =.07), and the parent-HCP
      relationship (p = .06) on the regimen. DISCUSSION: Parents and HCPs may come to
      the clinical encounter with markedly different illness representations.
      Establishing a partnership with parents by eliciting and acknowledging parental
      beliefs is an important component of improving disease management.

PMID- 17495573
TI  - Perceived prejudice in healthcare and women's health protective behavior.
AB  - BACKGROUND: The literature documents significant claims of experienced prejudice
      in healthcare delivery in relationship to ethnicity, race, female gender, and
      homosexual orientation. Studies link perceived prejudice with negative healthcare
      outcomes, particularly in hypertension, heart disease, depression, and human
      immunodeficiency virus or acquired immune deficiency syndrome. OBJECTIVES: To
      examine the impact of perceived prejudice in healthcare delivery on women's early
      cancer detection behavior and women's decisions to seek care for illness
      symptoms. METHODS: Community women stratified by age, income, education, and race
      or ethnicity were surveyed regarding healthcare visits and cancer detection
      behavior. Perceived and experienced prejudice in healthcare delivery was measured
      by the Perceived Prejudice in Health Care Scale and follow-up interview. RESULTS:
      Experienced prejudice in healthcare delivery was linked significantly with failed
      adherence to cancer screening guidelines and fewer provider visits for serious
      illness. After controlling for demographics, experienced prejudice explained
      significant variance in perceived access to care. Although many who experienced
      prejudice in relationship to their race, income level, sexual orientation, or a
      combination of these returned for healthcare services, others were alienated
      sufficiently to decrease their health protective behavior. DISCUSSION: Subjective
      perceptions of prejudice are a significant influence in women's health protective
      behaviors. These findings demonstrate that policies requiring healthcare teams to
      be trained in professional ethics and cultural competence are vital to the goal
      of quality in care delivery and are needed to achieve optimal healthcare outcomes
      for women.

PMID- 17495574
TI  - Performance obstacles of intensive care nurses.
AB  - BACKGROUND: The work environment of intensive care nurses may have substantial
      impact on both nursing outcomes and patient safety. The factors in a nurse's
      immediate work environment, in the local work context, have not been studied in
      detail to provide useful, specific information for work redesign efforts to
      improve nurse's work and patient safety. Performance obstacles are the factors
      that hinder intensive care nurses' capacity to perform their jobs and that are
      associated closely with their immediate work environment. OBJECTIVES: To identify
      the performance obstacles experienced by intensive care nurses in their work
      environment. METHODS: A multisite, cross-sectional study was conducted. Data were
      collected using a 36-item questionnaire and analyzed using univariate statistical
      analysis. The frequencies of performance obstacles reported by intensive care
      nurses were computed. RESULTS: Nurses (n = 272) from 17 intensive care units
      (ICUs) of seven hospitals in Wisconsin participated in the study. The most
      frequently experienced performance obstacles included noisy work environment
      (46%), distractions from families (42%), hectic (40%) and crowded work
      environments (37%), delay in getting medications from pharmacy (36%), spending
      considerable amount of time teaching families (34%), equipment not being
      available-someone else using it (32%), patient rooms not well-stocked (32%),
      insufficient workspace for completing paperwork (26%), seeking for supplies (24%)
      or patients' charts (23%), receiving many phone calls from families (23%), delay
      in seeing new medical orders (21%), and misplaced equipment (20%). DISCUSSION:
      Intensive care nurses experience a variety of performance obstacles in their work
      environment. Future research should investigate the impact of various performance
      obstacles on nursing workload, nursing quality of working life, and quality and
      safety of care, as well as the impact of interventions aimed at redesigning the
      work system of ICU nurses to remove performance obstacles.

PMID- 17495575
TI  - Visual graphical analysis: a technique to investigate symptom trajectories over
      time.
AB  - BACKGROUND: Research to address clinical symptoms and the way they change over
      time in an individual is of paramount importance to healthcare researchers who
      are interested in improving the quality of life for ill patients. However,
      typical statistical methods that rely on means can obscure individual
      trajectories of change. Visual graphical analysis (VGA) is a technique that can
      provide researchers with an alternative method of quantitative statistical
      analysis that is more sensitive to individual change and variation. OBJECTIVES:
      To (a) describe the use of VGA as a method to evaluate longitudinal data, (b)
      discuss challenges to using this method, and (c) offer recommendations for future
      research in which the method could be implemented. APPROACH: This methodological
      article uses data collected from a primary study to present the method of VGA.
      Daily self-reported sore mouth severity scores from patients receiving outpatient
      chemotherapy were used in this VGA. The steps of VGA include (a) determining
      inclusion criteria, (b) managing missing data, (c) creating visual graphs, (d)
      identifying specific patterns, and (e) performing validation and verification.
      DISCUSSION: Because symptoms occur differently for each patient, this method
      allows researchers to see symptom trajectories on an individual basis. Creation
      and analysis of longitudinal graphs could be used also to inspect other symptoms
      or clinical problems such as headaches, fatigue, constipation, nausea and
      vomiting, and psychological difficulties. The value of VGA is that it allows a
      researcher to study the patterns of an individual's experience, as opposed to
      averaging all individuals' responses over time. Although graphical analysis is
      exploratory in nature, it may lead to enhanced longitudinal recognition of
      symptoms that might not be identified otherwise by quantitative data analysis
      using summary statistics.

PMID- 17495576
TI  - Evaluation of an integrated communication skills training program for nurses in
      cancer care in Beijing, China.
AB  - BACKGROUND: Nurses have considerable needs for communication skills training in
      cancer care because of the general lack of education and training on oncology
      specific communication skills in Mainland China. OBJECTIVES: To evaluate the
      effectiveness of an integrated communication skills training program, in which an
      intensive learning session was combined with practice in the clinical unit to
      create a supportive ward atmosphere where nurses could practice skills in the
      workplace and obtain support of head nurses. METHODS: To implement the
      communication skills training for 129 nurses, a quasi-experimental research
      design with a nonequivalent control group was used. Measures, including basic
      communication skills, self-efficacy in oncology-specific communication skills,
      communication outcome expectancies, and self-perceived support for communication,
      were administered at pretraining evaluation, formative evaluation (1 month after
      training), and summative evaluation (6 months after training) in the training
      group. Formative evaluation was not administered in the control group. RESULTS:
      There was continued significant improvement in the overall basic communication
      skills, self-efficacy, outcome expectancy beliefs, and perceived support in the
      training group. No significant improvement was found in the control group over
      the same period. DISCUSSION: Nurses' communication skills could be developed and
      consolidated under the integrated communication skills training model.
      Development of effective interventions to change nurses' negative outcome
      expectancies in communication with cancer patients is needed in further study.

PMID- 17495578
TI  - Effects of acculturation on the reporting of depressive symptoms among Hispanic
      pregnant women.
AB  - BACKGROUND: Significant differences have been reported in the prevalence of
      depression between Mexicans and Mexican Americans. Whether the differences in
      prevalence are real or are the results of cultural bias in instrumentation is not
      known. OBJECTIVES: To examine the association between acculturation and the
      responses to the individual depressive symptom item of the Center for
      Epidemiologic Studies Depression Scale (CES-D). METHODS: The CES-D was
      administered to 395 Hispanic women during their 22-24 weeks' pregnancy clinic
      visit. Acculturation was defined by a subject's language preference of English or
      Spanish when completing the CES-D. Those who preferred English belong to the
      acculturated group and those who preferred Spanish are considered
      nonacculturated. Logistic regression was used to conduct differential item
      functioning (DIF) analysis for each of the 20 CES-D items to determine whether
      they operated differently between the acculturated Hispanic group and the
      nonacculturated Hispanic group. RESULTS: Reliability of the CES-D total score was
      .86 and .88 for the nonacculturated and acculturated groups, respectively. None
      of the items of the Depressed Affect Subscale showed DIF. However, DIF was found
      in four out of the seven items in the Somatic Activity Subscale and in three out
      of the four items in the Positive Affect Subscale. DISCUSSION: The results
      suggest that even within a homogenous Hispanic group of mostly Mexican Americans,
      responses to the CES-D differ by acculturation. The nonacculturated group are
      less likely to endorse somatic symptoms but more likely to endorse positive items
      than the acculturated group. Depression screening in this population needs to
      account for acculturation differences within the Hispanic group.

PMID- 17495577
TI  - Behavioral therapies trials: a case example.
AB  - BACKGROUND: Behavior change is integral to the prevention and treatment of many
      disorders associated with deleterious lifestyles. Rigorous scientific testing of
      behavior change interventions is an important goal for nursing research.
      APPROACH: The stage model for behavioral therapy development is recommended as a
      useful framework for evaluating behavior change strategies. The NIH model
      specifies three stages from initial testing of novel behavioral therapies to
      their dissemination in community settings. Definitions of each step in a Stage I
      trial and a case example of Mindfulness-Based Stress Reduction (MBSR) in
      therapeutic community treatment are provided. RESULTS: It is feasible to adapt a
      behavioral therapy such as MBSR using the stage model framework. Steps in the
      process include: (a) determining pilot study design and describing the
      population; (b) modifying the intervention and developing the manual; (c)
      training the teachers; (d) implementing a pilot study; and (e) monitoring
      treatment integrity. DISCUSSION: The development of behavior therapies requires
      the same scientific rigor used in pharmacotherapy research. Stage I of the model
      enables consideration of the "dose" of a behavioral intervention necessary to
      achieve behavior change in a defined population. The stage model offers an
      excellent approach to achieving rigor in a variety of potentially useful
      therapies of interest to nurse researchers.

PMID- 17495580
TI  - Evidence-based spine surgery.
AB  - STUDY DESIGN: Literature review. OBJECTIVE: To describe the state of the
      literature regarding the performance of lumbar fusion for low back pain due to
      degenerative disease of the spine. SUMMARY OF BACKGROUND DATA: The effectiveness
      and costs associated with spinal surgery have been a topic of significant debate
      in both the popular press and professional literature. METHODS: Evidence-based
      medicine techniques have been applied to many areas of spinal surgery. The
      results of these analyses are being used by practicing physicians, payors, and
      others to determine what procedures are appropriate for certain patient
      populations. RESULTS: This manuscript describes the methodology, strengths, and
      weaknesses of evidence-based medicine approaches to spinal surgery. The case for
      lumbar fusion as a treatment for chronic low back pain due to degenerative disc
      disease is described as an example. CONCLUSION: Evidence-based medicine is a
      useful tool for summarizing and grading the evidence available in the literature
      for or against a particular treatment strategy. Its utility is limited by the
      quality of the primary literature, and the absence of proof cannot be equated
      with the proof of absence.

PMID- 17495581
TI  - To err is human: quality and safety issues in spine care.
AB  - STUDY DESIGN: A review of issues linking advocacy, patient safety, and quality.
      OBJECTIVE: To heighten awareness of patient safety issues that require ongoing
      advocacy efforts by physicians treating spinal disorders. SUMMARY OF BACKGROUND
      DATA: The 1999 Institute of Medicine report "To Err is Human. Building a Safer
      Health System" was a landmark publication that vaulted patient safety into the
      limelight of public awareness and media attention. The American Academy of
      Orthopedic Surgeons had addressed the wrong site surgery issue with its Sign Your
      Site Program even before the Institute of Medicine report. Several professional
      medical societies involved in spine care have made advocating for patient safety
      a priority. METHODS: A summary of areas of advocacy efforts involving patient
      safety and quality. These include the Sign Your Site Program from the American
      Academy of Orthopedic Surgeons, Sign, Mark and X-ray from the North American
      Spine Society, Joint Commission on the Accreditation of Healthcare Organizations
      Universal Protocol, and technology assessment. Advocacy on the Federal, state,
      and local levels concerning patient safety is reviewed. RESULTS: Awareness of
      patient safety issues has increased. Several patient safety protocols (Sign Your
      Site, Sign, Mark and X-ray, and the Universal Protocol) are in place. There is
      increased monitoring of medical errors on the state and local, especially
      hospital, levels. CONCLUSIONS: Patient safety is an absolute provision of health
      care. Physicians need to set a personal example for compliance with existing
      patient safety systems such as the Universal Protocol and be active advocates for
      patient safety.

PMID- 17495582
TI  - SF-36 PCS benefit-cost ratio of lumbar fusion comparison to other surgical
      interventions: a thought experiment.
AB  - STUDY DESIGN: A retrospective review of prospectively collected data. OBJECTIVES:
      To review systematically the SF-36 PCS outcomes of a large data set, including
      several randomized clinical trials for lumbar spine fusion at 1 and 2 years after
      surgery. We also present for comparison a review of typical changes in SF-36 PCS
      in other surgical interventions (total knee replacement, total hip replacement,
      and coronary artery bypass surgery) to define the average reimbursement costs per
      PCS improvement with each of these interventions. SUMMARY AND BACKGROUND DATA:
      Data from 11 prospective multicenter studies (9 Food and Drug Administration
      Investigational Device Exemption, Randomized Prospective Clinical Trials, class 1
      data) accounted for the lumbar spine fusion group (n = 1826). Data for total knee
      replacement, total hip replacement, and coronary artery bypass surgery were
      obtained from a comprehensive review of the literature. METHODS: Comparisons of
      SF-36 PCS improvements were made at defined postoperative time points and with
      published study findings of other medical conditions. Reimbursement estimates
      (not including estimated physician and rehabilitation fees) for each surgical
      intervention were based on Centers for Medicare and Medicaid Services Medicare
      Provider Analysis and Review and All Payer Data (2002). Cost estimates were
      calculated for a minimal clinical important improvement (reimbursement
      dollars/mean PCS change *5.42 point PCS improvement). RESULTS: SF-36 PCS
      significantly improved at both 1 and 2 years following lumbar spine fusion
      surgery (P < 0.0001), and was comparable to the control surgical outcomes. With
      the use of data from Centers for Medicare and Medicaid Services Medicare Provider
      Analysis and Review and All Payer Data, hospital reimbursement averaged $15.2
      18.2K for lumbar spine fusion, $9.8-11.3K for total knee replacement, $9.6-11.3K
      for total hip replacement, and $9.8-11.3K for coronary artery bypass surgery.
      Calculations of reimbursement dollars to elicit minimum clinically important
      change in PCS of 5.42 points following surgery ranged from $6.1 to $7.3K for
      lumbar spine fusion, $5.7 to $6.6K for total knee arthroplasty, $3.9 to $4.5K for
      total hip replacement, and $18.2 to $22.5K for coronary artery bypass surgery.
      CONCLUSION: While the exact numbers may vary for each treatment based on the
      population studied and the cost estimates used, lumbar fusion cost per benefit
      achieved was very comparable to other well-accepted medical interventions (total
      hip replacement, total knee replacement, and coronary artery bypass surgery).

PMID- 17495583
TI  - Controlling costs: opportunities for physician-hospital collaborations and
      ventures.
AB  - STUDY DESIGN: Analysis of federal laws, regulations, and commentary relevant to
      gainsharing and other physician-hospital collaborations. Review of health, legal,
      and medical literature to identify relevant case studies, primarily from 2000 to
      the present. OBJECTIVE: To illustrate a number of physician-hospital
      collaboration and joint venture models to explore opportunities for physicians
      and hospital partners to enhance revenues and contain costs in the provision of
      health care. SUMMARY OF BACKGROUND DATA: There are numerous physician-hospital
      joint ventures throughout the United States and 8 approved gainsharing programs.
      Few comparisons of gainsharing as compared to other joint venture structures are
      available to hospitals and physicians. METHODS: A narrative review of health,
      legal, and business literature, regulations, and commentary to identify physician
      hospital collaborations and ventures as well as applicable regulatory
      authorities. RESULTS: There are numerous joint venture and collaboration models
      used throughout the country for physician-hospital collaborations with varying
      degrees of success. Eight approved gainsharing programs have been implemented.
      CONCLUSIONS: Physician-hospital collaborations, gainsharing, and joint ventures
      are expanding throughout the country in response to reimbursement pressures and
      movement of care into the ambulatory setting. These partnerships can be
      successful where there is sufficient alignment of interests to offset the
      operational and regulatory complexities that such partnerships present.

PMID- 17495584
TI  - Pay-for-performance: considerations in application to the management of spinal
      disorders.
AB  - STUDY DESIGN: Descriptive review. OBJECTIVES: To describe the role of pay-for
      performance as a health care policy that has a significant influence on the
      management of spinal disorders, and to consider parameters of quality measure
      that are likely to optimize the efficacy of a pay-for-performance system as
      applied to spine care. SUMMARY OF BACKGROUND DATA: Pay-for-performance
      arrangements have been adopted in many areas of medicine with limited evidence
      for improvement in quality of care. There is an important role for a system that
      will improve quality of care in the management of spinal disorders. The absence
      of accepted evidence-based approaches to the management of spinal disorders makes
      the choice of parameters to measure for quality difficult. RESULTS: Performance
      parameters to consider include a continuum of measures from process variables
      that focus on a discrete component of the health care experience, to outcome
      variables that encompass the end result of care. There are advantages and
      limitations to each parameter discussed. CONCLUSION: A pay-for-performance system
      in the management of spinal disorders should include both process variables that
      measure safety and outcome variables that reflect the end result of care.

PMID- 17495585
TI  - Technology assessment: approach and reimbursement.
AB  - STUDY DESIGN: Review of technology assessment process for novel spine patient
      care. OBJECTIVE: To discuss the issues surrounding the introduction of novel
      technologies for spine patient care. SUMMARY OF BACKGROUND DATA: The parties
      involved in the technology development and assessment process include clinicians,
      researchers, academic institutions, governmental organizations, and private
      health care payors. METHODS: Description of the responsibilities and processes of
      various parties involved in technology assessment. RESULTS: The process for
      introduction of novel spine technologies is complex and will become more
      efficient as each party involved increases its understanding of the roles played
      by all the others. CONCLUSIONS: The technology assessment process involves
      clinicians, researchers, governmental agencies, and private payors. All must work
      in concert for the efficient introduction of safe, efficacious, reasonable, and
      cost-effective novel treatments for spine patients.

PMID- 17495586
TI  - The spine service line: optimizing patient-centered spine care.
AB  - STUDY DESIGN: Literature review and expert opinion on the delivery of spine care.
      OBJECTIVE: Our objective was to describe the goals of a spine service line and
      encourage the implementation of a systems-based approach to spine care. The
      benefits to patients and institutions are discussed. SUMMARY OF BACKGROUND DATA:
      Spine care delivery and its associated costs are rising rapidly. There exists
      tremendous variability in the rate at which it is delivered. With so many options
      for spine care, patients are subject to decisions of providers with disparate
      backgrounds and expertise. This leads to inefficiencies in diagnosis and delivery
      of care. All these factors lead to increased costs of care of uncertain benefit
      and increased burden to society. METHODS: The literature on systems-based
      approaches to spine care was reviewed. Those relating to health care policy and
      recent clinical trials were emphasized. How these data work in a systems-based
      approach was described. Additionally, the authors' experiences working in and
      within a structured spine care system were related and included. RESULTS: We
      describe 3 spine care episodes and where each possesses particular inefficiencies
      that lead to increased costs without added value to the delivery of spine care.
      The primary episode is the start of the patient's painful incident. We propose a
      more uniform guidelines-based approach using appropriate (and similar) diagnostic
      testing and education. The secondary phase of care can be costly as more
      sophisticated diagnostic and treatment methods are instituted. Within an
      institution or spine care practice, matching the level of providers with the
      patients at this phase of care would lead to better utilization of resources.
      Additionally, benefits to the institution would be greater if managed properly.
      The third phase of care focuses on intervention with long-term benefits. We
      discuss the use of registry like data and analysis of outcomes on these patients.
      Agreement within a group or institution on operative indications would allow for
      more uniform analysis of these outcomes. Alternative revenue streams are also
      discussed. CONCLUSIONS: The patient with spinal disease is in need of high
      quality, proven, and efficient care. Using a systems-based approach, we can
      minimize escalating costs associated with inefficient health care and delivery.
      Cooperation between physicians and institutions is critical to this process.

PMID- 17495587
TI  - Physician-owned companies.
AB  - STUDY DESIGN: The author relates his experience in the development of a spinal
      implant development company (K2M) that is significantly advised by physicians.
      OBJECTIVES: To provide information about the development of a spinal implant
      company (K2M) advised by a group of professional spinal surgeons. To relate the
      federal laws (STARK and anti-kickback) as they pertain to surgeon-influenced
      companies. To discuss the role of a scientific advisory board. METHODS: A self
      developed company was developed together with significant, but minority physician
      financial input and majority scientific advice. RESULTS: A privately owned spinal
      implant development corporation (K2M) was developed 3 years ago. Physician
      financial participation was less than 20% (Stark laws state no more than 40%).
      Users of product are greater than 60% non-investor physicians. The development of
      a large scientific advisory board has been very influential in product
      development. CONCLUSIONS: A privately owned spinal implant company (K2M) has been
      developed strictly within Federal laws. Its board of scientific advisors that
      receives recompense commissurate only with effort significantly impacts the
      company policy.

PMID- 17495588
TI  - Counterpoint: physician-industry relationships can be ethically established, and
      conflicts of interest can be ethically managed.
AB  - STUDY DESIGN: Review of the nature of conflicts of interest in physician-industry
      relationships, with a focus on the efforts to ethically manage physician-industry
      relationships. OBJECTIVE: To illustrate the perspective that physician-industry
      relationships can be ethically established, and conflicts of interest can be
      ethically managed. SUMMARY OF BACKGROUND DATA: The interest in considering the
      appropriateness of physician-industry relationships has recently become focused
      on spine surgery. Many of the conflicts of interest inherent to these
      relationships have been interpreted as problematic, and have been scrutinized by
      the media, industry, medical and legal professions, and Federal government.
      METHODS: The basis for conflicts of interest, manner in which bias may be
      introduced, and methods to reduce bias are presented. The potential risks and
      benefits to patients that are inherent to physician-industry relationships are
      considered. A framework, developed by medical ethicists, is provided to guide
      analysis of conflicts of interest in physician-industry relationships. RESULTS:
      Collaboration between spine surgeons and industry is necessary to improve patient
      care. The conflicts of interest that often arise in physician-industry
      relationships must be recognized, and keenly managed in order to eliminate the
      risk and maximize the benefit to the patient. Ethical management of conflicts
      must include disclosure. To preserve patient autonomy, management should also
      include a discussion of the quality of the medical evidence on which treatment
      recommendations are made. Guidelines from industry and medical professional
      organizations, including the "Standards of Professionalism" currently under
      development by the American Academy of Orthopedic Surgery, are also expected to
      aid in the ethical establishment and management of conflicts of interest.
      CONCLUSIONS: Careful consideration of conflicts of interest in physician-industry
      relationships has provided an opportunity to review our goals as physicians in
      society, and to continue collaborative advancement of our field for the benefit
      of our patients.

PMID- 17495589
TI  - Threats to scientific advancement in clinical practice.
AB  - STUDY DESIGN: Point/counterpoint. OBJECTIVE: To facilitate debate regarding
      conflicts of interest and ethical considerations in physician/industry
      relationships. SUMMARY OF BACKGROUND DATA: We find ourselves working in a health
      care system in which nearly $2 trillion are spent, only to rank 37th in world
      health. That much money at stake piques peoples' interest, and various parties,
      without loyalty to the Hippocratic principles, will find opportunities to gain
      financially. Clearly, current health expenditures do not always coincide with
      better outcomes. Yet some believe that over 20% of the gross national product
      will be necessary to maintain our health care system in the future. Medical
      liability causes a paradoxical situation: physicians are at times driven to use
      the newest technology and perform many diagnostic tests, for fear of litigation.
      This practice is often independent of the best evidence. METHODS: Literature
      search and experience. RESULTS: The nature or magnitude of conflict(s) of
      interest influences the risk of bias in research. It is important to acknowledge
      and disclose these potential conflicts while recognizing that the existence of
      such conflict does not necessarily adversely affect the quality of the research.
      CONCLUSIONS: Conflict of interest need not be a conflict of the mind and is not
      an evil. Physicians need to disclose all relationships to industry and/or other
      potential conflicts in order to maintain the trust of one's community, and in
      order to advance the best science.

PMID- 17495590
TI  - Measuring outcomes in back care.
AB  - STUDY DESIGN: Narrative review. OBJECTIVE: Describe current issues of outcomes
      assessment in spine research, with a focus on their application to advocacy
      oriented research. SUMMARY OF BACKGROUND DATA: Outcomes measurement in back pain
      has advanced substantially over the past decade. METHODS: Qualitative assessment
      of outcomes assessment methods when used in advocacy settings. RESULTS:
      Researchers and clinicians now have multiple instruments that can assess patient
      outcomes with adequate psychometric properties. The domains generally assessed
      include: biologic measures (range of motion, fusion rate); patient-reported
      outcomes (functional status, quality of life); process measures (hospital days,
      medication use); and outcomes of interest to society (days off work, health care
      costs). When research is conducted in the context of advocacy work, care is
      needed to avoid introduction of bias into the work. Bias in outcomes assessment
      can occur through multiple phases of the research process, including selection of
      the research question, study design, measurement, choice of the outcome measures
      used, and analysis. Bias can also occur in assessing outcomes across studies in
      literature synthesis. CONCLUSIONS: Transparency in research methods and clear
      communication can avoid many of the described pitfalls in outcomes assessment,
      allowing researchers to advocate appropriately for improvement in patient care.

PMID- 17495591
TI  - A nested case-control study of sexual practices and risk factors for prevalent
      HIV-1 infection among young men in Kisumu, Kenya.
AB  - OBJECTIVES: To investigate sexual practices and risk factors for prevalent HIV
      infection among young men in Kisumu, Kenya. GOAL: The goal of this study was to
      identify behaviors associated with HIV in Kisumu to maximize the effectiveness of
      future prevention programs. STUDY DESIGN: Lifetime sexual histories were
      collected from a nested sample of 1337 uncircumcised participants within the
      context of a randomized controlled trial of male circumcision to reduce HIV
      incidence. RESULTS: Sixty-five men (5%) tested positive for HIV. Multiple
      logistic regression revealed the following independent predictors of HIV: older
      age, less education, being married, being Catholic, >4 lifetime sex partners,
      prior treatment for an STI, sex during partner's menstruation, ever practicing
      bloodletting, and receipt of a medical injection in the last 6 months. Prior HIV
      testing and postcoital cleansing were protective. CONCLUSIONS: This analysis
      confirms the importance of established risk factors for HIV and identifies
      practices that warrant further investigation.

PMID- 17495592
TI  - Sexually transmitted infections in Western Europe among HIV-positive men who have
      sex with men.
AB  - BACKGROUND: Since 1996, there has been a resurgence in sexually transmitted
      infections (STIs) among men who have sex with men (MSM) in Western Europe. This
      has coincided with a significant decrease in HIV-associated mortality following
      the introduction of highly active antiretroviral therapies (HAART) and a
      corresponding increase in the number of MSM living with HIV. Levels of
      unprotected anal intercourse have also increased. In this article, we use STI
      surveillance data from a number of Western European countries to better
      understand the contribution of HIV-positive MSM to the recent increase in STIs.
      METHODS: Published literature, surveillance reports, and ad hoc publications
      relating to HIV prevalence trends and STIs among HIV-positive MSM in Western
      Europe were reviewed. RESULTS: Post-HAART, HIV prevalence among community samples
      of MSM ranged from 5% to 18%. HIV prevalence among MSM diagnosed with an STI was
      substantially higher. On average, HIV prevalence among MSM diagnosed with
      syphilis in 11 countries was 42% (range 14%-59%). Most HIV-positive MSM with
      syphilis were aware of their HIV status. In England and Wales, 32% of MSM with
      gonorrhea were HIV-positive in 2004. Outbreaks of lymphogranuloma venereum have
      been documented in 9 countries; HIV-positive MSM accounted for 75% of cases on
      average (range 0%-92%). Cases of sexually transmitted hepatitis C have been
      predominantly identified among HIV-positive MSM in Rotterdam, Paris, Amsterdam,
      and the United Kingdom. CONCLUSIONS: In Western Europe, STIs have been
      disproportionately diagnosed among HIV-positive MSM post-HAART. Improved survival
      coupled with serosorting among HIV-positive MSM appears to explain the high
      prevalence of HIV among MSM with STIs. STI transmission among HIV-positive men
      will have contributed substantially to increasing STI trends seen among MSM in
      Western Europe, since 1996. These findings highlight the need for routine STI
      testing among HIV-positive MSM as well as safer sex messages highlighting the
      implications of STI coinfection.

PMID- 17495594
TI  - Lipid metabolism and metabolic disease: defining new targets.

PMID- 17495595
TI  - Plasminogen activator inhibitor-1, adipose tissue and insulin resistance.
AB  - PURPOSE OF REVIEW: Plasminogen activator inhibitor (PAI)-1 is a physiological
      inhibitor of plasminogen activators (urokinase and tissue types) and vitronectin.
      It is synthesized by adipose tissue, and its levels in plasma are increased in
      obesity and reduced with weight loss. Circulating PAI-1 level predicts
      development of type 2 diabetes, suggesting that it may be causally related to
      development of obesity. A role for PAI-1 in development of obesity has only
      partially been established, however. This review summarizes current knowledge,
      gives context to developments thus far and discusses controversies. RECENT
      FINDINGS: In addition to its role in atherothrombosis, PAI-1 might be involved in
      adipose tissue development. PAI-1 is produced by ectopic fat depots under the
      influence of inducers. Among the most recently described inducers are
      inflammation, oxidative stress and circadian clock protein. PAI-1 may play
      several roles in contributing to obesity: through indirect effects on insulin
      signalling, by influencing adipocyte differentiation and by regulating
      recruitment of inflammatory cells within adipose tissue. SUMMARY: These recent
      findings emphasize the involvement of PAI-1 in controlling the biology of adipose
      tissue; PAI-1 is an attractive new therapeutic target to retard the metabolic
      complications that accompany obesity.

PMID- 17495596
TI  - The role of neutral lipases in human adipose tissue lipolysis.
AB  - PURPOSE OF REVIEW: The aim of this article is to describe the relative roles of
      hormone sensitive lipase and adipose triglyceride lipase in human fat cell
      lipolysis. RECENT FINDINGS: Until recently, only hormone sensitive lipase was
      considered important for the regulation of lipolysis within fat cells. Recent
      rodent studies have suggested that adipose triglyceride lipase may, however, be
      more important. The few human adipose triglyceride lipase studies that have been
      published point to species differences between humans and rodents. Selective
      inhibition of hormone sensitive lipase in human fat cells completely counteracts
      hormone-activated lipolysis, though there is a considerable (>>50%) residual
      nonhormonal (basal) lipolysis. In rodents, adipose triglyceride lipase enzyme
      activity is stimulated by a cofactor termed CGI-58. In the absence of CGI-58,
      lipase activity in fat cells is much higher for hormone sensitive lipase than
      adipose triglyceride lipase. Hormone sensitive lipase expression is regulated by
      obesity and body weight reduction (decreased and increased, respectively), but
      this is not the case for adipose triglyceride lipase. A role of adipose
      triglyceride lipase in human lipolysis is suggested by studies of gene
      polymorphisms. SUMMARY: Two lipases the 'old' hormone sensitive lipase and the
      'new' adipose triglyceride lipase are of importance for the regulation of
      lipolysis in rodent fat cells. In humans, adipose triglyceride lipase seems
      essential for maintaining basal lipolytic activity, while hormone sensitive
      lipase is the enzyme most responsive to stimulated lipolysis.

PMID- 17495597
TI  - Concerted actions of cholesteryl ester transfer protein and phospholipid transfer
      protein in type 2 diabetes: effects of apolipoproteins.
AB  - PURPOSE OF REVIEW: Type 2 diabetes frequently coincides with dyslipidemia,
      characterized by elevated plasma triglycerides, low high-density lipoprotein
      cholesterol levels and the presence of small dense low-density lipoprotein
      particles. Plasma lipid transfer proteins play an essential role in lipoprotein
      metabolism. It is thus vital to understand their pathophysiology and determine
      which factors influence their functioning in type 2 diabetes. RECENT FINDINGS:
      Cholesteryl ester transfer protein-mediated transfer is increased in diabetic
      patients and contributes to low plasma high-density lipoprotein cholesterol
      levels. Apolipoproteins A-I, A-II and E are components of the donor lipoprotein
      particles that participate in the transfer of cholesteryl esters from high
      density lipoprotein to apolipoprotein B-containing lipoproteins. Current evidence
      for functional roles of apolipoproteins C-I, F and A-IV as modulators of
      cholesteryl ester transfer is discussed. Phospholipid transfer protein activity
      is increased in diabetic patients and may contribute to hepatic very low-density
      lipoprotein synthesis and secretion and vitamin E transfer. Apolipoprotein E
      could stimulate the phospholipid transfer protein-mediated transfer of surface
      fragments of triglyceride-rich lipoproteins to high-density lipoprotein, and
      promote high-density lipoprotein remodelling. SUMMARY: Both phospholipid and
      cholesteryl ester transfer proteins are important in very low and high-density
      lipoprotein metabolism and display concerted actions in patients with type 2
      diabetes.

PMID- 17495598
TI  - Monocyte chemotactic protein-1 and its role in insulin resistance.
AB  - PURPOSE OF REVIEW: In obesity, there is a strong link between increased adipose
      tissue mass and development of insulin resistance in tissues such as liver and
      muscle. Under these conditions, adipose tissue synthesizes various pro
      inflammatory chemokines such as monocyte chemotactic protein-1. This review
      provides a summary of recent knowledge on the role of monocyte chemotactic
      protein-1 in adipose tissue inflammation and insulin resistance. RECENT FINDINGS:
      Monocyte chemotactic protein-1 is a proinflammatory adipokine that is believed to
      play a role in the pathogenesis of obesity and diabetes. New in-vitro data
      demonstrate that monocyte chemotactic protein-1 has the ability to induce insulin
      resistance in adipocytes and skeletal muscle cells. By using mice that either
      overexpress monocyte chemotactic protein-1 or are deficient in monocyte
      chemotactic protein-1 or its receptor, exciting new insights have been obtained
      into the role of monocyte chemotactic protein-1 in adipose tissue inflammation
      and insulin resistance. SUMMARY: Monocyte chemotactic protein-1 is an adipokine
      with insulin-resistance-inducing capacity that is related to increased adipose
      tissue mass in obesity and insulin resistance. It plays an important role in
      adipose tissue inflammation by recruiting macrophages into fat. Monocyte
      chemotactic protein-1 is thus a therapeutic target, and may represent an
      important factor linking adipose tissue inflammation, obesity and type 2
      diabetes.

PMID- 17495599
TI  - Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic
      and cardiovascular disease.
AB  - PURPOSE OF REVIEW: Adiponectin is secreted exclusively by adipocytes, aggregates
      in multimeric forms, and circulates at high concentrations in blood. This review
      summarizes recent studies highlighting cellular effects of adiponectin and its
      role in human lipid metabolism and atherosclerosis. RECENT FINDINGS: Adiponectin
      is an important autocrine/paracrine factor in adipose tissue that modulates
      differentiation of preadipocytes and favors formation of mature adipocytes. It
      also functions as an endocrine factor, influencing whole-body metabolism via
      effects on target organs. Adiponectin multimers exert differential biologic
      effects, with the high-molecular-weight multimer associated with favorable
      metabolic effects (i.e. greater insulin sensitivity, reduced visceral adipose
      mass, reduced plasma triglycerides, and increased HDL-cholesterol). Adiponectin
      influences plasma lipoprotein levels by altering the levels and activity of key
      enzymes (lipoprotein lipase and hepatic lipase) responsible for the catabolism of
      triglyceride-rich lipoproteins and HDL. It thus influences atherosclerosis by
      affecting the balance of atherogenic and antiatherogenic lipoproteins in plasma,
      and by modulating cellular processes involved in foam cell formation. SUMMARY:
      Recent studies emphasize the role played by adiponectin in the homeostasis of
      adipose tissue and in the pathogenesis of the metabolic syndrome, type 2
      diabetes, and atherosclerosis. These pleiotropic effects make it an attractive
      therapeutic target for obesity-related conditions.

PMID- 17495600
TI  - Fatty acid transport proteins.
AB  - PURPOSE OF REVIEW: Fatty acid transport proteins are a family of proteins
      involved in fatty acid uptake and activation. This review summarizes recent
      progress in elucidating the function of fatty acid transport proteins. RECENT
      FINDINGS: Recent experiments clearly establish FATP1 as a regulated fatty acid
      transporter in both adipose tissue and muscle with important roles in energy
      homeostasis, thermogenesis and insulin resistance. Knockout of FATP5 in mice show
      it to be a bifunctional protein required for both hepatic fatty acid uptake and
      bile acid reconjugation. The most striking phenotype of FATP4 deletion is a
      defect in skin homeostasis, which may be due to its very long chain acyl-coenzyme
      A synthetase activity. Fatty acid transport proteins are increasingly being
      recognized as multifunctional proteins that can mediate the uptake of fatty acids
      as well as catalyze the formation of coenzyme A derivatives using long-chain and
      very-long chain fatty acids, bile acids and bile acid precursors as substrates.
      SUMMARY: Modulation of fatty acid transport protein function can result in
      altered energy homeostasis and insulin sensitivity, defective skin homeostasis,
      and altered bile acid metabolism. Both fatty acid uptake and enzymatic activity
      of fatty acid transport proteins likely contribute to these phenotypes. Future
      studies are needed to better understand the molecular mechanism of fatty acid
      transport protein function and the physiological role of FATP2, FATP3, and FATP6.

PMID- 17495602
TI  - Oxysterols: functional significance in fetal development and the maintenance of
      normal retinal function.
AB  - PURPOSE OF REVIEW: Recent findings extend the biologic activities of oxysterols
      as ligands for nuclear receptors to a role in morphogenesis during fetal
      development and to a role in the metabolism of photooxidation products of
      cholesterol in the retina. RECENT FINDINGS: A 1000-fold increase of the 27
      hydroxy metabolite of 7-dehydrocholesterol in the plasma of children with Smith
      Lemli-Opitz syndrome imply that intermediates in cholesterol synthesis follow
      alternate pathways of metabolism that generate novel oxysterols. A mouse model
      also finds an increase in sterol intermediates as the proximate cause of
      dysmorphisms. A role for oxysterols in the effects of Sonic hedgehog protein
      focuses on their role in normal fetal development. Both CYP27A1 and CYP46A1 are
      expressed in primate retina indicating that local metabolism of 7-ketocholesterol
      to nontoxic derivatives is important for preventing retinal degeneration.
      SUMMARY: Recent data expand the functional roles of oxysterols to fetal
      development and to the detoxification of oxidation products of cholesterol. This
      review shifts the focus of attention from studies of their ligand-binding
      activity to studies of animal models that indicate a number of important biologic
      effects during fetal development and during the aging process.

PMID- 17495601
TI  - Lipids in the heart: a source of fuel and a source of toxins.
AB  - PURPOSE OF REVIEW: How do lipids arrive in the heart and other tissues? This
      review focuses on new information on pathways of lipid uptake into the heart.
      RECENT FINDINGS: Fatty acids, the major cardiac fuel, are obtained from either
      lipoproteins or free fatty acids associated with albumin. The heart is the tissue
      with the most robust expression of lipoprotein lipase, and recent data attest to
      the importance of this enzyme in supplying optimal amounts of fatty acids for the
      heart. Genetic deletion of CD36 also shows that this transporter is important for
      cardiac uptake of lipids. Retinoid acquisition by the heart involves pathways
      parallel to those used for fatty acid uptake: a pathway for acquisition of core
      lipoprotein retinyl ester and another for nonlipoprotein retinol. Dilated
      lipotoxic cardiomyopathy is the consequence of excess lipid uptake. SUMMARY:
      Genetic modifications that affect lipid uptake, oxidation, and storage are being
      exploited to elucidate the pathophysiology of cardiomyopathies and to discover
      how lipids relate to heart failure in humans with obesity and diabetes mellitus.
      This information is likely to lead to new diagnostic categories of cardiomyopathy
      and more pathophysiologically appropriate treatments.

PMID- 17495603
TI  - Bile acids, farnesoid X receptor, atherosclerosis and metabolic control.
AB  - PURPOSE OF REVIEW: Bile acids are amphiphilic molecules synthesized from
      cholesterol exclusively in the liver that are essential for effective absorption
      of dietary fat. In addition to this 'classical role', bile acids act as
      signalling molecules that control their own metabolism by activating the nuclear
      receptor, farnesoid X receptor. RECENT FINDINGS: Recent work demonstrates that
      farnesoid X receptor exerts metabolic control beyond bile acid homeostasis,
      notably effects on HDL, triglyceride and glucose metabolism. Farnesoid X receptor
      influences insulin sensitivity of tissues that are not part of the enterohepatic
      circulation, for example, adipose tissue. Certain metabolic effects in the liver
      appear to be mediated via farnesoid X receptor-stimulated release of an
      intestinal growth factor. In addition, novel signalling pathways independent of
      farnesoid X receptor have been identified that may contribute to bile acid
      mediated metabolic regulation. SUMMARY: Farnesoid X receptor represents a
      potentially attractive target for treatment of various aspects of the metabolic
      syndrome and for prevention of atherosclerosis. Yet, in view of its pleiotropic
      effects and apparent species-specificity, it is evident that successful
      interference of the farnesoid X receptor signalling system will require the
      development of gene-specific and/or organ-specific farnesoid X receptor
      modulators and extensive testing in human models of disease.

PMID- 17495604
TI  - Endothelial lipase and the metabolic syndrome.
AB  - PURPOSE OF REVIEW: Several in-vitro and in-vivo animal studies indicate that
      endothelial lipase plays a key role in the intravascular remodeling of
      lipoproteins, particularly HDL. This review integrates this body of knowledge
      with more recent data in humans linking endothelial lipase to HDL metabolism and
      other features of the metabolic syndrome. RECENT FINDINGS: Human studies
      generally support the involvement of endothelial lipase in modulating plasma HDL.
      The association between endothelial lipase and metabolism of apolipoprotein B
      containing lipoproteins in humans, however, has not been entirely consistent with
      previous findings in vitro and in animals. Finally, elevated plasma endothelial
      lipase has been associated with abdominal obesity and hypertension, and there is
      now compelling evidence that inflammation and in-vivo regulation of endothelial
      lipase may be intrinsically related. SUMMARY: Accumulating evidence indicates
      that endothelial lipase plays a role in the etiology of the atherogenic plasma
      lipoprotein profile characteristic of the metabolic syndrome. Increased
      endothelial lipase activity is linked to the underlying proinflammatory state in
      this condition. Further studies are required, however, to define the extent to
      which endothelial lipase contributes to the dyslipidemia of the metabolic
      syndrome relative to other important regulating factors, such as lipoprotein
      lipase, hepatic lipase, and cholesterol ester transfer protein.

PMID- 17495605
TI  - Unravelling the functional significance of PCSK9.
AB  - PURPOSE OF REVIEW: Proprotein convertase subtilisin kexin type 9 (PCSK9) has
      emerged as a potential target for lowering plasma LDL cholesterol levels. This
      review summarizes recent studies published in print or online before January 2007
      which have investigated the functional significance of this intriguing protease.
      RECENT FINDINGS: Increasing interest in PCSK9 has given rise to landmark
      epidemiological studies, the generation of animal models, the discovery of new
      human mutations, as well as numerous in-vitro studies. These studies have helped
      to unravel the molecular functions of PCSK9. SUMMARY: Mutations of PCSK9 are
      associated either with hypercholesterolemia or with hypocholesterolemia. In the
      latter case, the incidence of coronary heart disease is reduced, thereby
      demonstrating that low LDL cholesterol levels from birth are highly beneficial.
      PCSK9 promotes the degradation of the LDL receptor in hepatocytes apparently both
      intracellularly and by being a secreted protein that can bind the LDL receptor
      and be internalized. By virtue of its role as a major inhibitor of the LDL
      receptor, PCSK9 is a promising therapeutic target. Specific PCSK9 pharmacological
      inhibitors may prove to be useful in amplifying the well documented benefits of
      statins.

PMID- 17495606
TI  - Intestinal cholesterol transport proteins: an update and beyond.
AB  - PURPOSE OF REVIEW: Various studies have delineated the causal role of dietary
      cholesterol in atherogenesis. Strategies have thus been developed to minimize
      cholesterol absorption, and cholesterol transport proteins found at the apical
      membrane of enterocytes have been extensively investigated. This review focuses
      on recent progress related to various brush-border proteins that are potentially
      involved in alimentary cholesterol transport. RECENT FINDINGS: Molecular
      mechanisms responsible for dietary cholesterol and plant sterol uptake have not
      been completely defined. Growing evidence, however, supports the concept that
      several proteins are involved in mediating intestinal cholesterol transport,
      including SR-BI, NPC1L1, CD36, aminopeptidase N, P-glycoprotein, and the caveolin
      1/annexin-2 heterocomplex. Other ABC family members (ABCA1 and ABCG5/ABCG8) act
      as efflux pumps favoring cholesterol export out of absorptive cells into the
      lumen or basolateral compartment. Several of these cholesterol carriers influence
      intracellular cholesterol homeostasis and are controlled by transcription
      factors, including RXR, LXR, SREBP-2 and PPARalpha. The lack of responsiveness of
      NPC1L1-deficient mice to ezetimibe suggests that NPC1L1 is likely to be the
      principal target of this cholesterol-lowering drug. SUMMARY: The understanding of
      the role, genetic regulation and coordinated function of proteins mediating
      intestinal cholesterol transport may lead to novel ways of treating
      cardiovascular disease.

PMID- 17495607
TI  - Characterization of apolipoprotein A-V structure and mode of plasma
      triacylglycerol regulation.
AB  - PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of death in the
      USA, and hypertriglyceridemia represents an independent risk factor contributing
      to its premature onset. Apolipoprotein (apo)A-V has been shown to be a potent
      regulator of plasma triacylglycerol. We highlight structural aspects of apoA-V
      and discuss recent findings that provide mechanistic insight into its function as
      a regulator of plasma triacylglycerol metabolism. RECENT FINDINGS: Recent
      findings indicate that apoA-V is comprised of two independently folded domains.
      Fluorescence spectroscopy and truncation analysis revealed that the carboxyl
      terminal region functions in apoA-V lipid binding, consistent with its known
      association with plasma lipoproteins. An indirect triacylglycerol-modulating
      effect of apoA-V has been attributed to heparan sulfate proteoglycan binding, as
      confirmed by structural studies. Furthermore, apoA-V has been shown to interact
      with cell surface receptors, potentially facilitating lipoprotein particle
      endocytosis. SUMMARY: Several features of apoA-V, including extremely low plasma
      concentration, lack of correlation with plasma cholesterol levels despite its
      association with HDL, and insolubility at neutral pH in the absence of lipid, are
      unlike those of other exchangeable apolipoproteins. Current and future studies of
      apoA-V will help to shed light on the molecular basis whereby this protein
      functions to modulate plasma lipid homeostasis.

PMID- 17495609
TI  - Current world literature. Lipid metabolism.

PMID- 17495608
TI  - Cholesterol metabolism, apolipoprotein E, adenosine triphosphate-binding cassette
      transporters, and Alzheimer's disease.
AB  - PURPOSE OF REVIEW: Recent evidence suggests that cholesterol metabolism
      participates in the pathogenesis of Alzheimer's disease. Apolipoprotein E is the
      main lipid carrier in the brain and the best-established risk factor for late
      onset Alzheimer's disease. Intracellular cholesterol levels influence the
      generation of amyloid-beta peptides, the toxic species thought to be a primary
      cause of Alzheimer's disease. Finally, compounds that modulate cholesterol
      metabolism affect amyloid-beta generation. This review summarizes data linking
      apolipoprotein E and adenosine triphosphate-binding cassette transporters to
      aspects of cholesterol metabolism and Alzheimer's disease pathogenesis. RECENT
      FINDINGS: In vivo, the lipidation status of apolipoprotein E affects amyloid-beta
      burden in mice with Alzheimer's disease, which appears to caused by the
      modulation of amyloid-beta deposition or clearance rather than amyloid-beta
      production. State-of-the-art in-vivo assays reveal that amyloid-beta is cleared
      from the brain by multiple pathways. Members of the adenosine triphosphate
      binding cassette superfamily of transporters regulate lipid homeostasis and
      apolipoprotein metabolism in the brain, and may affect Alzheimer's disease
      pathogenesis by modulating apolipoprotein E lipidation as well as intracellular
      sterol homeostasis. SUMMARY: Proteins involved in brain cholesterol metabolism
      may affect the pathogenesis of Alzheimer's disease. Compounds that modulate the
      expression of these proteins may be of therapeutic benefit in Alzheimer's
      disease.

PMID- 17495610
TI  - Nutrition and metabolism.

PMID- 17495611
TI  - Genetics and molecular biology: micro RNAs are welcome to the lipid field.

PMID- 17495612
TI  - New interests in the measurement of plasma adiponectin concentration.

PMID- 17495613
TI  - Hyperlipidaemia and cardiovascular disease: statin update.

PMID- 17495614
TI  - Therapy and clinical trials.

PMID- 17495616
TI  - Acute disseminated encephalomyelitis: an acute hit against the brain.
AB  - PURPOSE OF REVIEW: In this review, the possible etiology, clinical
      characteristics, diagnosis, and treatment of acute disseminated encephalomyelitis
      (ADEM) are discussed. ADEM is a para- or postinfectious autoimmune demyelinating
      disease of the central nervous system and has been considered a monophasic
      disease. The highest incidence of ADEM is observed during childhood. RECENT
      FINDINGS: Over the last decade, many cases of multiphasic ADEM have been
      reported. The occurrence of relapses potentially poses a diagnostic dilemma for
      the treating physician, as it may be difficult to distinguish multiphasic ADEM
      from multiple sclerosis (MS). Many retrospective patient studies have thus
      focused on the clinical and paraclinical features of ADEM and have attempted to
      define specific diagnostic criteria. Additionally, several experimental models
      have provided insight with respect to the pathogenic relation of an infectious
      event and subsequent demyelinating autoimmunity. SUMMARY: Capitalizing on
      experience based on a large body of well characterized patient data collected
      both cross-sectionally and longitudinally, pharmacotherapy has been improved and
      mortality and comorbidities due to ADEM have been reduced. Unfortunately, the
      pathogenic events that trigger the initial clinical attack, and possibly pave the
      way for ongoing relapsing disease, remain unknown. Clinically applicable
      diagnostic criteria are still lacking.

PMID- 17495617
TI  - Neuromyelitis optica.
AB  - PURPOSE OF REVIEW: We review recent advances in neuromyelitis optica, an
      idiopathic inflammatory demyelinating disease of the central nervous system
      predominantly affecting optic nerves and spinal cord. We concentrate on a
      recently identified serum antibody biomarker, neuromyelitis optica immunoglobulin
      G (NMO-IgG), which distinguishes neuromyelitis optica from multiple sclerosis.
      RECENT FINDINGS: NMO-IgG is detected by indirect immunofluorescence. Its presence
      and specificity for neuromyelitis optica was confirmed in diverse populations.
      Seropositivity is now incorporated into new diagnostic criteria for neuromyelitis
      optica. Testing for this biomarker has suggested that the neuromyelitis optica
      spectrum is broader than previously recognized. Recently, the molecular target of
      NMO-IgG was identified as aquaporin-4. Immunopathologic studies suggest that loss
      of aquaporin-4 immunostaining is detectable in early lesions of neuromyelitis
      optica. A B-cell-specific monoclonal antibody, rituximab, may be an effective
      treatment even in patients not responding to other treatments. SUMMARY: Clinical,
      radiologic, and immunologic features distinguish neuromyelitis optica from other
      severe cases of multiple sclerosis. NMO-IgG is the first specific marker for a
      central nervous system demyelinating disease. The discovery of aquaporin-4 as the
      putative target of NMO-IgG, and recent data suggesting that aquaporin-4-specific
      antibodies are pathogenic may enhance our understanding of idiopathic
      inflammatory demyelinating diseases and their treatment.

PMID- 17495618
TI  - Multiple sclerosis: the environment and causation.
AB  - PURPOSE OF REVIEW: We review current thinking on the aetiology of multiple
      sclerosis, how genetic susceptibility interacts with environmental risk factors
      at the population level, multiple sclerosis-associated risk factors and
      contemporary causation theory. RECENT FINDINGS: Two large genomic studies have
      confirmed the unambiguous associations with the DRB1 and DQB alleles of the human
      leucocyte antigen class II region. No other region with genome-wide significance
      has been identified. Family-based genetic epidemiological approaches have found
      no evidence of nongenetic transmissibility. This indicates that the action of the
      environment in influencing multiple sclerosis risk is operative at a
      macroenvironmental or population level, and not within families or the
      microenvironment. Environmental factors receiving renewed attention include
      vitamin D status, Epstein-Barr virus infection and smoking. Bradford Hill's
      criteria for causation have been modified and should be adopted as a framework
      for demonstrating causation in relationship to multiple sclerosis. SUMMARY:
      Multiple sclerosis is a complex disease because of interaction between genes and
      the environment. Any theory of causation for a specific agent will have to be
      congruent with the biology of the disease.

PMID- 17495619
TI  - Natural history of multiple sclerosis: risk factors and prognostic indicators.
AB  - PURPOSE OF REVIEW: To highlight progress in the description of the natural course
      and prognosis of multiple sclerosis. RECENT FINDINGS: The general evolution of
      multiple sclerosis is now well known at the level of patient groups.
      Characteristics of relapses early in the disease and the occurrence of a
      progressive phase seemed to be the most reliable prognostic factors. Recent works
      suggest that the progressive phase in multiple sclerosis could be an age
      dependent, degenerative process, independent of previous relapses, and that the
      initial course of the disease does not substantially influence age at disability
      milestones. By contrast, a younger age at disease onset strongly correlates with
      a younger age when reaching disability landmarks, confirming that even if it
      takes longer for younger patients to accumulate irreversible disability, they are
      disabled at a younger age than patients with later onset. Multiple sclerosis
      might be considered as one disease with different clinical phenotypes, rather
      than an entity encompassing several distinct diseases. SUMMARY: Overall course
      and prognosis in multiple sclerosis is most likely to be related to age and the
      occurrence of the progressive phase of the disease, rather than to relapses or
      other clinical parameters. Individual prognosis remains hazardous.

PMID- 17495620
TI  - Cognitive impairment in multiple sclerosis.
AB  - PURPOSE OF REVIEW: For a long time, cognitive impairment in multiple sclerosis
      patients has been considered less important than, for instance, physical
      disability. This is no longer true because of the crucial role that cognitive
      deficits play in the good day-to-day adjustment of patients. This review
      highlights recent progress made in this area. A special focus lies on studies
      investigating the neural correlates of cognitive impairment in multiple sclerosis
      patients as detectable by conventional, quantitative and functional magnetic
      resonance imaging. RECENT FINDINGS: Measures of information-processing speed
      appear to be the most robust and sensitive markers of cognitive impairment in
      multiple sclerosis patients. Recent studies demonstrate that single,
      predominantly speed-related cognitive tests may be superior to extensive and time
      consuming test batteries in screening overall cognitive decline. Quantitative
      magnetic-resonance-imaging findings suggest the extent of subtle tissue damage in
      normal-appearing white and grey matter to correlate best with the severity of
      cognitive impairment in multiple sclerosis patients. SUMMARY: From
      neuropsychological test data, and findings from magnetic resonance imaging and
      functional magnetic resonance imaging it is evident that cognitive impairment in
      multiple sclerosis is not just the result of tissue destruction, but rather a
      balance between tissue destruction, tissue repair, and adaptive functional
      reorganization.

PMID- 17495621
TI  - Combination therapies for multiple sclerosis: scientific rationale, clinical
      trials, and clinical practice.
AB  - PURPOSE OF REVIEW: To outline the scientific rationale for combination therapy in
      multiple sclerosis and to discuss the evidence for combination treatment
      strategies from animal models and clinical trials of multiple sclerosis. RECENT
      FINDINGS: Experiments conducted in experimental autoimmune encephalomyelitis have
      recently shown beneficial effects of numerous combination therapies. The
      combination of approved and experimental drugs and two or more experimental
      agents may positively impact clinical disease activity, inflammation within the
      central nervous system, and neurorepair. Clinical trials are currently underway
      to establish the therapeutic efficacy and safety of various combination therapies
      for multiple sclerosis patients. SUMMARY: More effective therapies are needed to
      treat multiple sclerosis. There are good scientific rationales for the use of
      combination therapy in multiple sclerosis, and the pharmacologic principles for
      evaluating and understanding their actions are available. The evaluation of
      specific combination therapies in the controlled setting of clinical trials
      should be a priority in clinical multiple sclerosis research.

PMID- 17495622
TI  - Treatment and treatment trials in multiple sclerosis.
AB  - PURPOSE OF REVIEW: This review focuses on advances in current and novel treatment
      approaches in multiple sclerosis. RECENT FINDINGS: New therapeutic approaches in
      multiple sclerosis are emerging. Orally available treatment strategies are more
      acceptable for patients and may improve adherence to therapy. An oral formulation
      of glatiramer acetate failed to demonstrate efficacy in a clinical trial, but
      other promising compounds are on the horizon, such as FTY720. Advances are
      currently being made in use of therapeutic monoclonal antibodies that
      specifically target key molecules involved in the immunopathogenesis of multiple
      sclerosis. Natalizumab directed against the adhesion molecule very late antigen-4
      represents the first specific antibody to be added to our therapeutic
      armamentarium for multiple sclerosis. Further evidence that immunomodulation
      should be initiated as early as possible has been reported. SUMMARY: Treatment of
      multiple sclerosis has changed dramatically over the past decade. Enhanced
      understanding of the immunopathological processes that underlie the disease,
      advances in biotechnology and development of powerful magnetic resonance imaging
      technologies, together with improvements in clinical trial design have led to a
      variety of valuable therapeutic approaches, which are currently being studied in
      detail.

PMID- 17495623
TI  - Myelin regeneration in demyelinating disorders: new developments in biology and
      clinical pathology.
AB  - PURPOSE OF REVIEW: The following article reviews recent advances in remyelination
      biology and its presentation in demyelinating diseases such as multiple
      sclerosis. It is based primarily on articles published during 2006. RECENT
      FINDINGS: The principal themes are the identity and properties of remyelinating
      cells; the role of inflammation in remyelination; and the complexity of and
      redundancy within the signalling environment regulating remyelination. SUMMARY:
      Central nervous system remyelination is mainly mediated by oligodendrocyte
      precursor cells, although subventricular zone-derived cells contribute to the
      repair of periventricular lesions. Oligodendrocyte precursor cells may
      differentiate into astrocytes and Schwann cells following injury and exhibit more
      stem cell-like features than previously recognized. A complex matrix of
      environmental factors, including cytokines, chemokines and growth factors, act
      upon oligodendrocyte precursor cells, causing their activation and eventual
      differentiation into remyelinating oligodendrocytes. Inflammatory cells
      contribute by providing components of the signalling matrix and by the phagocytic
      removal of myelin debris. Many factors within the signalling environment have
      redundant functions - a feature of regeneration with implications for developing
      remyelination therapies. Advances in remyelination biology have been accompanied
      by more detailed analyses of remyelination in multiple sclerosis and important
      translational developments, including the ability to identify myelin by positron
      emission tomography.

PMID- 17495624
TI  - Migraine: gene mutations and functional consequences.
AB  - PURPOSE OF REVIEW: Genetic and functional studies of mutations in familial
      hemiplegic migraine reveal a major role for disturbed ion transport. Gene
      identification in common, multifactorial migraine remains challenging. RECENT
      FINDINGS: Several new mutations have been identified in FHM1, FHM2 and FHM3
      genes. Functional consequences of familial hemiplegic migraine mutations point to
      an important role for cortical spreading depression in migraine pathophysiology.
      New genetic approaches have been tested in common migraine - novel chromosomal
      loci - but no gene variants have been identified. SUMMARY: Identification and
      analysis of gene mutations in familial hemiplegic migraine revealed a major role
      for disturbed ion transport in this disorder. Cellular and transgenic mouse
      models of familial hemiplegic migraine genes suggest that increased potassium and
      glutamate play a role in the pathophysiology of the disorder. Despite progress,
      no genes have been discovered for common migraine.

PMID- 17495625
TI  - New insights into migraine: application of functional and structural imaging.
AB  - PURPOSE OF REVIEW: Functional neuroimaging in headache patients has
      revolutionized our understanding of these syndromes. Further insights into the
      pathophysiology of headache syndromes have been provided by innovative
      neuroimaging analysis using structural data. This review highlights the recent
      advances made in studying migraine using neuroimaging techniques. RECENT
      FINDINGS: Several independent studies have reinforced the crucial role for the
      brainstem in acute and probably also chronic migraine. Recently described
      structural abnormalities in the visual network of motion-processing areas could
      account for, or be caused by, the cortical hyperexcitability observed in
      migraineurs. Although data from morphometric studies are heterogeneous, a recent
      study suggests an increased density of brainstem structures and decreased grey
      matter in pain-transmitting areas in migraine patients. SUMMARY: Given the rapid
      advances in functional neuroimaging, in particular newer techniques such as voxel
      based morphometry and magnetic resonance spectrometry, functional imaging
      continues to play a significant role and opens new avenues in targeting the
      neural substrates in individual primary headache syndromes.

PMID- 17495626
TI  - Patent foramen ovale, stroke, and cardiovascular disease in migraine.
AB  - PURPOSE OF REVIEW: We will review the literature on the association between
      migraine with patent foramen ovale, stroke, and coronary heart disease. RECENT
      FINDINGS: The prevalence of patent foramen ovale in patients with migraine with
      aura is significantly higher than in nonmigraine controls and migraineurs without
      aura. However, there is currently no evidence to support a causal relationship.
      Migraine with aura has been consistently associated with increased risk of
      ischemic stroke in several epidemiologic studies. Migraine with aura is
      associated with a more unfavourable cardiovascular risk profile and recent data
      suggest that the association between migraine with aura and stroke may extend to
      overall cardiovascular disease. Identification of migraine patients at particular
      risk for stroke or other vascular events is impossible based on current
      knowledge. SUMMARY: Migraine with aura and patent foramen ovale have higher
      coincidences than expected by chance only. It is possible that both conditions
      are inherited together. Until now there has been no evidence from placebo
      controlled randomized trials that closure of patent foramen ovale improves
      migraine with aura. There is increasing evidence that migraine with aura is not
      only a risk factor for ischemic stroke but also for myocardial infarction and
      other ischemic vascular events.

PMID- 17495627
TI  - Muscle pain in the head: overlap between temporomandibular disorders and tension
      type headaches.
AB  - PURPOSE OF REVIEW: A variety of painful problems can affect the muscles in the
      head and face. Both temporomandibular disorders and tension-type headaches are
      believed to have a significant contribution from the skeletal muscles and have
      several clinical features in common. It still unclear, however, to what extent
      these two prevalent disorders are separate entities or have similar
      pathophysiological background. RECENT FINDINGS: There is now reasonably good
      evidence that myofascial temporomandibular disorder patients are more likely to
      have a tension-type headache problem and vice versa, but the overlap is not
      complete. Studies have documented similarities regarding sensitization of the
      nociceptive pathways, dysfunction of the endogenous pain modulatory systems as
      well as contributing genetic factors, but there are also a number of distinct
      differences between temporomandibular disorders and tension-type headaches that
      need to be considered. SUMMARY: Using the current classification systems,
      myofascial temporomandibular disorder pain and tension-type headache disorders do
      overlap and appear to share many of the same pathophysiological mechanisms, but
      it would be premature to consider them as identical entities since the importance
      of, for example, the affected muscles and associated function and genetic
      background needs to be established. Orofacial pain and headache specialists
      should collaborate to further develop diagnostic procedures and management
      strategies of temporomandibular disorders and tension-type headaches.

PMID- 17495628
TI  - Medication-overuse headache: where are we now?
AB  - PURPOSE OF REVIEW: Many important studies on medication-overuse headache have
      been published in the last year. Some of them investigated the pathophysiology of
      headache chronicity, others focused on evaluation of risk factors. The
      International Headache Society revised the classification criteria. We provide a
      summary of the new findings and concepts. RECENT FINDINGS: Medication-overuse
      headache was previously defined by the International Headache Society as a
      chronic headache which occurs following overuse of headache drugs and improves
      after withdrawal. Hence, the improvement of headache after withdrawal was
      mandatory for diagnosis. The new appendix criteria appeared last year and
      established a broader concept of medication-overuse headache no longer requiring
      improvement after discontinuation of medication overuse. Several large population
      based longitudinal studies clearly demonstrated that overuse of any kind of acute
      headache medication is the main risk factor leading to development of chronic
      headache. Imaging studies provided new important insights into the
      pathophysiology of headache chronicity. New treatment strategies have been
      suggested. SUMMARY: Recent data provide better insight into pathophysiology of
      medication-overuse headache. Epidemiological studies clearly demonstrate the
      necessity of establishing a predictive model for early recognition of patients at
      high risk to intervene early and avoid development of chronic headache.

PMID- 17495629
TI  - The increasing importance of inflammation in neurological disease.

PMID- 17495630
TI  - Inflammation and ischaemic stroke.
AB  - PURPOSE OF REVIEW: Inflammation is implicated in ischaemic stroke as a general
      cardiovascular risk factor, a possible immediate trigger, a component (and
      possible exacerbating factor) of the response to tissue injury, a marker of
      future risk, and as a therapeutic target. Each aspect is reviewed. RECENT
      FINDINGS: Evidence of epidemiological association of inflammatory markers,
      particularly C-reactive protein, has accrued, but the independence of
      inflammation from more conventional risk indicators is under question. Other
      inflammatory markers are associated with intermediate phenotypes such as
      hypertension. Tissue inflammation in atherosclerotic plaque is of probable
      relevance in identifying recently symptomatic carotid disease. Both humoral and
      cellular inflammation are evident following stroke, with evidence that these
      responses may exacerbate tissue injury. Blockade of interleukin-1, or of
      neutrophil chemotaxis, has reduced infarct volume in models of stroke but has yet
      to show benefit in clinical trials. Other anti-inflammatory strategies are
      promising. SUMMARY: Inflammation is implicated in several aspects of acute
      ischaemic stroke. It remains to be established whether the inflammatory response
      is a truly independent risk factor in general, or whether specific anti
      inflammatory interventions are beneficial either in prevention or acute
      treatment.

PMID- 17495631
TI  - Comparative immunopathogenesis of acute disseminated encephalomyelitis,
      neuromyelitis optica, and multiple sclerosis.
AB  - PURPOSE OF REVIEW: Advanced immunopathological techniques hold promise for more
      precise diagnosis of idiopathic demyelinating diseases of the central nervous
      system. We review recent progress in differentiating and understanding the
      disease mechanisms of acute disseminated encephalomyelitis, neuromyelitis optica,
      and classical multiple sclerosis. RECENT FINDINGS: Four distinct
      immunopathological patterns have been described in multiple sclerosis patients,
      potentially implicating different inflammatory, demyelinating, and apoptotic
      mechanisms. A specific serum biomarker, neuromyelitis optica immunoglobulin G, is
      strongly associated with neuromyelitis optica and identifies patients with severe
      optic nerve and spinal cord lesions with specific pathological features such as
      eosinophilic and neutrophilic inflammatory infiltrates, necrosis, vascular
      hyalinization, and extensive vasculocentric immunoglobulin and complement
      deposition. This biomarker targets the water channel aquaporin-4, which is lost
      in neuromyelitis optica lesions. Acute disseminated encephalomyelitis still has
      no validated clinical diagnostic criteria but its perivenous pathological
      findings distinguish it from multiple sclerosis and neuromyelitis optica.
      SUMMARY: The clinically heterogeneous group of idiopathic inflammatory
      demyelinating diseases of the central nervous system is characterized by several
      immunopathological patterns that suggest the involvement of diverse pathogenic
      effector mechanisms. Future advances in experimental pathology, immunology,
      molecular genetics, and neuroimaging, as well as the discovery of specific
      biomarkers, will more precisely define these disorders and lead to better
      targeted therapies.

PMID- 17495632
TI  - Therapeutic approaches to inflammation in neurodegenerative disease.
AB  - PURPOSE OF REVIEW: According to the neuroinflammatory hypothesis of
      neurodegenerative diseases, drugs with an anti-inflammatory mode of action should
      slow the disease progression. Here we review recent advances in our understanding
      of one such disorder, Parkinson's disease, in which anti-inflammatory drugs are
      now becoming a new therapeutic focus. RECENT FINDINGS: The involvement of
      inflammatory mechanisms in Parkinson's disease has been revealed through in-vitro
      and in-vivo experimental studies supported by pathological and epidemiological
      findings. Several of the demonstrated inflammatory mechanisms are shared by other
      neurodegenerative disorders but some Parkinson's disease-specific mechanisms have
      also emerged. These include inflammatory stimulation by interaction of alpha
      synuclein with microglia and astrocytes and a suppressive action by nonsteroidal
      anti-inflammatory drugs on dopamine quinone formation. SUMMARY: It can be
      anticipated that a more detailed understanding of neuroinflammatory mechanisms in
      Parkinson's disease will lead to new cellular and molecular targets, which may,
      in turn, permit design of Parkinson's disease modifying drugs. Future treatment
      may involve combination therapies with drugs directed at both inflammatory and
      non-inflammatory mechanisms.

PMID- 17495633
TI  - Bibliography. Current world literature. Demyelinating diseases.

PMID- 17495635
TI  - Intra-uterine adhesions and fertility outcome: how to optimize success?
AB  - PURPOSE OF REVIEW: To review the etiology, diagnosis, and clinical manifestations
      of intra-uterine adhesions and to address treatment with a specific focus on
      fertility outcome. RECENT FINDINGS: Intra-uterine adhesions can cause recurrent
      pregnancy loss and infertility. The gravid or recently postpartum uterus is
      particularly susceptible to adhesion formation following instrumentation. While
      sonohysterography and hysterosalpingography are useful as screening tests of
      intra-uterine adhesions, hysteroscopy remains the mainstay of diagnosis and
      treatment. Hysteroscopic lysis of adhesions with scissors, electrosurgery, or
      laser can restore the size and shape of the endometrial cavity. Significantly
      obliterated cavities may require multiple procedures to achieve a satisfactory
      anatomical result. Postoperative mechanical distention of the endometrial cavity
      and hormonal treatment to facilitate endometrial regrowth appear to decrease the
      high rate of adhesion reformation. Newer antiadhesive barriers may also prevent
      the recurrence of intra-uterine adhesions. Endometrial development can remain
      stunted due to a scant amount of residual functioning endometrium and fibrosis.
      Potential pregnancy complications, especially placenta accreta, after the
      treatment of intra-uterine adhesions should be anticipated and discussed with the
      patient. SUMMARY: Diagnosis and treatment of intra-uterine adhesions are integral
      to the optimization of fertility outcomes. Favorable results in terms of
      pregnancy and live birth rates can be expected after hysteroscopic adhesiolysis.

PMID- 17495636
TI  - The impact of dietary oestrogens on male and female fertility.
AB  - PURPOSE OF REVIEW: Modern consumer needs have stimulated a vast expansion in the
      dietary supplement market, in an attempt to improve general well being and
      prevent, rather than cure, disease. Isoflavones form a large part of this market.
      Their oestrogenic properties are still largely unknown and must be thoroughly
      researched to ensure they cause no adverse effects, particularly on hormone
      dependent reproductive physiology. RECENT FINDINGS: As a result of the increasing
      availability of phytoestrogens, research into their actions now covers a very
      wide field, many of which impact on reproductive potential. Time of exposure is
      crucial, as is interaction with other dietary components. Their putative role as
      chemoprotective agents has been expanded in recent years which may have an
      indirect impact on fertility by decreasing mortality rates in both men and women.
      SUMMARY: Phytoestrogens are still a current research topic in reproduction and
      fertility. Genistein is a putative therapeutic tool in cancer treatment although
      this must be considered along with evidence that it may cause DNA damage in
      sperm, depending on the concentration. The effects of phytoestrogen in the body
      are not limited to oestrogenic action. Much more epidemiological data are
      required to interpret current molecular studies, and those of previous years.

PMID- 17495637
TI  - The impact of male factor on recurrent pregnancy loss.
AB  - PURPOSE OF REVIEW: The present paper reviews the current literature on the impact
      of male factor on recurrent pregnancy loss. RECENT FINDINGS: Most clinicians
      focus their evaluation of recurrent pregnancy loss on the female, without much,
      if any, consideration of the other half of the couple - the male. Yet, the male
      contributes one-half of the genes for the embryo. Recent literature demonstrates
      that the male contributes to recurrent pregnancy loss due to genetic factors,
      semen factors or due to other factors such as age. SUMMARY: Recurrent pregnancy
      loss results as a factor of a couple. This paper emphasizes the contribution of
      the male to implantation failure, miscarriage, and congenital anomalies suggested
      by recent literature. The current data are preliminary. With further
      investigation, evaluation of the male may be considered a routine part of the
      evaluation in the near future.

PMID- 17495638
TI  - Reproductive performance of women with mullerian anomalies.
AB  - PURPOSE OF REVIEW: This review discusses current diagnostic techniques for
      mullerian anomalies, reproductive outcome data, and management options in
      reproductive-age women. RECENT FINDINGS: Multiple retrospective studies have
      investigated reproductive outcomes with mullerian anomalies, but few current
      prospective studies exist. Uterine anomalies are associated with normal and
      adverse reproductive outcomes such as recurrent pregnancy loss and preterm
      delivery, but not infertility. Furthermore, unicornuate, didelphic, bicornuate,
      septate, arcuate, and diethylstilbestrol-exposed uteri have their own
      reproductive implications and associated abnormalities. Common presentations of
      mullerian anomalies and current diagnostic techniques are reviewed. Surgical
      intervention for mullerian anomalies is indicated in women with pelvic pain,
      endometriosis, obstructive anomalies, recurrent pregnancy loss, and preterm
      delivery. Although surgery for most uterine anomalies is a major intervention,
      the uterine septum is preferentially managed with a hysteroscopic procedure.
      Several recent studies and review articles discuss management of the septate
      uterus in asymptomatic women, infertile women, and women with a history of poor
      reproductive outcomes. Current assessment of reproductive outcomes with uterine
      anomalies and management techniques is warranted. SUMMARY: Mullerian anomalies,
      especially uterine anomalies, are associated with both normal and adverse
      reproductive outcomes, and management in infertile women remains controversial.

PMID- 17495639
TI  - The impact of cesarean birth on subsequent fertility.
AB  - PURPOSE OF REVIEW: Recently, the rate of cesarean delivery has increased to 25
      30% of all births, the highest rate ever reported in the USA. Primary cesarean
      deliveries, especially elective procedures, mainly contribute to this increase.
      Currently, controversy concerning elective cesarean delivery is an area of
      growing debate. Women should be well informed about the benefits and risks of on
      demand cesarean delivery. This may be problematic, however, due to the limited
      current scientific data on the benefits and risks. One of the issues causing
      debate is the association between cesarean section and subsequent infertility. In
      the present review, we aim to analyze the evidence for the impact of cesarean
      delivery on subsequent fertility. RECENT FINDINGS: Cesarean section has been
      reported to be associated with decreased subsequent fertility. Recent studies,
      which have tried to explain this association, suggest that this is most probably
      voluntary or due to some other biases, or possible confounding factors, which are
      due to organic or psychosocial effects of an emergency cesarean section or labor
      preceding the cesarean delivery. SUMMARY: Elective cesarean section does not
      appear to cause infertility. What we need now, however, are more qualitative
      studies to determine the contribution of cesarean section per se on fecundity.

PMID- 17495640
TI  - The effect of oral contraceptives on assisted reproductive technology [corrected]
      cycles.
AB  - PURPOSE OF REVIEW: To summarize the available data regarding the value of oral
      contraceptive pill addition in ovarian stimulation schemes used for in-vitro
      fertilization. RECENT FINDINGS: In agonists cycles, a decreased incidence of
      ovarian cyst formation is expected in patients pretreated with the oral
      contraceptive pill after gonadotropin-releasing hormone agonist administration
      compared to those treated according to a long follicular protocol. In antagonist
      cycles, oral contraceptive pill pretreatment appears to be feasible and has been
      used for programming cycle initiation. Solid evidence regarding its effect on the
      probability of pregnancy is, however, currently lacking. SUMMARY: The optimal use
      of oral contraceptive pretreatment as well as its effect on in-vitro
      fertilization outcome have not yet been fully explored. The effect of oral
      contraceptive pill pretreatment is worth further investigation in properly
      designed trials.

PMID- 17495641
TI  - New advances in ovulation induction.
AB  - PURPOSE OF REVIEW: To review recent advances in ovulation induction. RECENT
      FINDINGS: Aromatase inhibitors can replace clomiphene citrate as ovulation
      inducing substances. The most widely used aromatase inhibitor for this purpose is
      letrozole and the optimal dose is 5 mg daily for 5 days. Compared to clomiphene
      citrate, it is associated with a thicker endometrium and a better pregnancy rate.
      It is as effective as gonadotropin but yet less expensive. The overall rates of
      congenital malformation among newborns conceived after infertility treatment with
      letrozole or clomiphene citrate are similar. When letrozole is combined with
      gonadotropin, it leads to lower gonadotropin requirements with pregnancy rates
      comparable to gonadotropin treatment alone. Another promising aromatase inhibitor
      is anastrazole. Recent evidence suggests that luteinizing hormone activity in
      human menopausal gonadotropin modifies follicular development so that fewer
      intermediate-sized follicles develop. Compared to the use of follicular
      stimulating hormone only, human menopausal gonadotropin is associated with less
      ovarian hyperstimulation. SUMMARY: Aromatase inhibitors are alternative drugs to
      clomiphene or gonadotropin for ovulation induction or superovulation.

PMID- 17495642
TI  - The impact of luteinizing hormone in assisted reproduction: a review.
AB  - PURPOSE OF REVIEW: Although the key role of luteinizing hormone in ovarian
      function, the promotion of follicular growth and maturation, is widely
      acknowledged, its usefulness as a predictor of ovarian status, and as a
      supplement during fertility treatment, remains controversial. RECENT FINDINGS:
      Luteinizing hormone alone is not an effective predictor of ovarian function. In
      combination with follicle-stimulating hormone, as the so-called follicle
      stimulating hormone: luteinizing hormone ratio, it serves as a useful marker of
      ovarian status. Although published data on luteinizing hormone supplementation
      during ovarian hyperstimulation are somewhat limited, recent well-designed
      studies suggest a beneficial effect of: (1) luteinizing hormone supplementation
      for women with inadequate responses to follicle-stimulating hormone-only
      stimulation; (2) in primarily young patients with low baseline luteinizing
      hormone levels and, consequently, insufficient remaining endogenous luteinizing
      hormone concentration during pituitary suppression; and (3) in older women with
      higher baseline luteinizing hormone levels and age-appropriate ovarian function,
      who require higher luteinizing hormone thresholds, even during pituitary
      suppression. SUMMARY: Luteinizing hormone levels, as a component of the follicle
      stimulating hormone: luteinizing hormone ratio, contribute to the assessment of
      ovarian function, whereas the supplementation of luteinizing hormone on an
      individualized basis, in carefully selected patients, improves outcomes of
      ovarian stimulation with gonadotropins.

PMID- 17495643
TI  - Effects of gonadotropin-releasing hormone agonists and antagonists on luteal
      function.
AB  - PURPOSE OF REVIEW: This review addresses the effects of gonadotropin-releasing
      hormone agonists and antagonists on various aspects of the luteal phase. RECENT
      FINDINGS: Recent studies have shown that use of both gonadotropin-releasing
      hormone agonists and antagonists during in-vitro fertilization cycles leads to
      alterations in the hormonal profiles of the luteal phase as well as changes in
      endometrial histology. Gonadotropin-releasing hormone agonists are effective in
      triggering final oocyte maturation and reducing the incidence of ovarian
      hyperstimulation syndrome. Ongoing pregnancy rates are excellent after
      gonadotropin-releasing hormone agonist trigger when luteal phase and early
      pregnancy supplementation with estradiol and progesterone is provided.
      Gonadotropin-releasing hormone agonists have recently been used for luteal phase
      support in in-vitro fertilization cycles. SUMMARY: Although gonadotropin
      releasing hormone agonists and antagonists are clinically useful, they may have
      adverse effects on luteal function. Luteal phase supplementation significantly
      improves clinical outcomes in in-vitro fertilization cycles because it may
      correct some of these detrimental effects. Use of gonadotropin-releasing hormone
      agonist to induce oocyte maturation is beneficial to patients who are at
      increased risk for ovarian hyperstimulation syndrome. The key factor in achieving
      favorable ongoing pregnancy rates with use of gonadotropin-releasing hormone
      agonist to induce oocyte maturation appears to be adequate luteal phase support.

PMID- 17495644
TI  - Role of chemokines in the endometrium and in embryo implantation.
AB  - PURPOSE OF REVIEW: Chemokines are well known for their roles in the immune
      system; convincing evidence has emerged demonstrating a broader role for
      chemokines in the endometrium, particularly during embryo implantation. This
      review highlights the evidence on newly defined roles for chemokines in the
      endometrium during embryo implantation, with particular focus on those chemokines
      expressed by the endometrium. RECENT FINDINGS: The highly regulated temporal and
      spatial expression of chemokines in the endometrium leads not only to specific
      recruitment and activation of appropriate leucocytes but also coordinates the
      precisely orchestrated invasion of trophoblasts through the decidua and maternal
      vasculature. Results to date implicate chemokine signalling at the maternal
      foetal interface in important processes during implantation and placentation,
      such as leucocyte recruitment and controlled trophoblast invasion. Unravelling
      such actions of chemokines in the endometrium has provided new insights into
      these complex processes. SUMMARY: Disturbances of chemokine production,
      processing, or actions are likely to contribute to dysfunction of implantation
      and placentation, with implications for early pregnancy loss and disturbed
      placental and foetal development. More research into altered chemokine function
      in such conditions may provide leads for new clinical interventions.

PMID- 17495645
TI  - How can we improve current blastocyst grading systems?
AB  - PURPOSE OF REVIEW: To give an overview of the current status and future
      directions of blastocyst transfer and outcome with particular focus on markers of
      blastocyst quality and their relationship with implantation. RECENT FINDINGS: In
      addition to morphological markers, future embryo grading systems, in general, and
      blastocyst grading systems, in particular, will be based upon metabolic, genetic
      and epigenetic markers that will increase their efficiency. Metabolic markers
      such as soluble human leukocyte antigen-G, analysis of specific gene mutations in
      the trophectoderm by real-time multiplex polymerase chain reaction and analysis
      by microarray of differential gene expression will be operational in the near
      future for accurate blastocyst grading and selection. SUMMARY: Gamete and embryo
      quality as well as culture conditions affect blastocyst formation and quality.
      Characteristics of the zygote and the cleavage-stage embryo determine the
      developmental potential of the embryo up to the blastocyst stage. There appears
      to be a strong relationship between blastocyst quality and implantation. Accurate
      grading is important for selection of the most implantation-competent blastocyst.
      Similar to grading systems used in the cleavage-stage embryo, current blastocyst
      grading systems are mainly based upon morphological characteristics.
      Incorporation of metabolic, genetic and epigenetic markers will undoubtedly
      improve the selection process, making it possible to transfer a single blastocyst
      yielding high pregnancy rates.

PMID- 17495646
TI  - The impact of uterine artery embolization on fertility and pregnancy outcome.
AB  - PURPOSE OF REVIEW: Uterine artery embolization for management of symptomatic
      fibroids is an effective and increasingly popular treatment option. There are
      several studies evaluating the effects of uterine artery embolization on later
      pregnancies; however, the effects on fertility are still largely uncertain. This
      paper reviews the current literature on the effects of this technique on
      fertility and pregnancy outcome. RECENT FINDINGS: Two recent studies have
      reported pregnancy rates following uterine artery embolization in women seeking
      pregnancy. A small, third study reported preliminary results in a randomized
      controlled trial comparing uterine artery embolization with myomectomy in women
      wishing to preserve fertility. SUMMARY: The body of medical literature supports
      use of uterine artery embolization as an effective treatment for symptoms of
      vaginal bleeding and pelvic pressure from uterine fibroids. Patient selection is
      critical in determining the appropriateness of this treatment option. Myomectomy
      remains the standard of care for women with symptomatic fibroids seeking
      fertility preservation.

PMID- 17495647
TI  - Long-term use of gonadotropin-releasing hormone analogues before IVF in women
      with endometriosis.
AB  - PURPOSE OF REVIEW: To discuss the relationship between endometriosis and
      infertility, the impact of endometriosis on assisted reproductive techniques and
      also the benefits of prolonged use of gonadotropin-releasing hormone analogue
      before IVF in women with endometriosis. RECENT FINDINGS: The available evidence
      suggests that endometriosis is strongly associated with infertility. Many studies
      indicate lower pregnancy and implantation rates even in assisted reproductive
      cycles in women with endometriosis. It is well known that medical suppression of
      endometriosis does not appear to be warranted for endometriosis-associated
      infertility. Prolonged pretreatment with gonadotropin-releasing hormone analogue
      before IVF has been reported to improve clinical pregnancy rates in infertile
      women with endometriosis. SUMMARY: Based on the recently published data,
      infertile women with endometriosis may benefit from long-term pretreatment of
      gonadotropin-releasing hormone analogue prior to IVF.

PMID- 17495648
TI  - Bibliography. Current world literature. Fertility.

PMID- 17495650
TI  - EMF dosimetry and biophysical aspects relevant to setting exposure guidelines.
      Proceedings of an international workshop. March 20-22, 2006. Berlin, Germany.

PMID- 17495651
TI  - Different basic dosimetric quantities for the characterization of exposure to low
      frequency electric and magnetic fields and the implication for practical exposure
      conditions and guidelines.
AB  - In this paper, the different quantities for characterizing human exposure at
      extremely low frequencies (ELF) up to 100 kHz are described. It is explained how
      the incident field is disturbed by the human body and how the in-situ fields and
      current densities are created in the body. Incident electric and magnetic fields
      are treated separately. Incident field characteristics such as homogeneity, time
      dependence, and polarization and body characteristics such as dimensions, shape,
      and position will influence the induced quantities. The use of in situ fields or
      of induced current densities to set the basic restrictions is discussed. The
      methods for deriving the reference levels from the basic restrictions in the
      international standards such as ICNIRP and IEEE guidelines are mentioned.
      Elliptical human models have been typically used in the past. In recent years,
      high-resolution anatomical models have become available. In this case maximum
      induced field levels or current densities can be determined for each organ. The
      validity of using elliptical or high-resolution anatomical models to derive
      reference levels is discussed. Special attention is paid to non-uniform (such as
      domestic exposure) or partial exposure of the human body.

PMID- 17495652
TI  - Numerical dosimetry ELF: accuracy of the method, variability of models and
      parameters, and the implication for quantifying guidelines.
AB  - In situ electric fields and current densities are investigated by numerical
      simulations for exposure to ELF electric and magnetic fields. Computations are
      based on the finite-difference time-domain method (FDTD). The computational
      uncertainty is determined by comparison of analytical and numerical results and
      amounts to a worst-case expanded uncertainty (95% confidence interval) of +/-9.89
      dB for both dosimetric quantities (E, J). Detailed investigations based on the
      Visible Human body model with a resolution of 2 mm show a strong influence of the
      tissue boundaries on the simulation results, which is caused by the numerical
      method. For the tissue specific in situ electric field and current density
      changes in excess of 10 dB are observed when comparing the results with and
      without evaluation of the dosimetric quantities at tissue boundaries. Moderate
      sensitivities with respect to tissue boundaries are observed only for low
      conductivity tissues when evaluating the in situ electric field whereas this
      behavior is observed for high conductivity tissues when evaluating the current
      density. For exposure to a 50 Hz magnetic field corresponding to the ICNIRP
      reference level, the simulated current density for central nervous system (CNS)
      tissue is in compliance with the ICNIRP guidelines. Exposure to a 50 Hz electric
      field may exceed the ICNIRP basic restriction for CNS tissue at least in a worst
      case scenario (grounded human body, vertical electric field, tissue boundaries
      included for the evaluation of the current density). The in situ electric field
      is the more stable dosimetric quantity with respect to changes of the tissue
      conductivity of the Visible Human body model. The maximum conductivity
      sensitivity coefficient amounts to +122% for the current density whereas the
      maximum sensitivity coefficient for the in situ electric field is -20%. For
      electric field exposure the in situ electric field remains comparable (-6% to 
      4%), the averaged current density change ranges from -57% to -16% for the tissues
      under investigation. Magnetic field exposure of a scaled model of a five year old
      child leads to a decrease of the dosimetric quantities (J: -74% to -45%, E: -42%
      to -23%) compared to the Visible Human results.

PMID- 17495653
TI  - Assessment of complex EMF exposure situations including inhomogeneous field
      distribution.
AB  - Assessment of exposure to time varying electric and magnetic fields is difficult
      when the fields are non-uniform or very localized. Restriction of the local
      spatial peak value below the reference level may be too restrictive. Additional
      problems arise when the fields are not sinusoidal. The objective of this review
      is to present practical measurement procedures for realistic and not too
      conservative exposure assessment for verification of compliance with the exposure
      guidelines of ICNIRP. In most exposure situations above 10 MHz the electric field
      (E) is more important than the magnetic field (B). At frequencies above 500 MHz
      the equivalent electric field power density averaged over the body is the most
      relevant indicator of exposure. Assessment of specific absorption rate (SAR) is
      not needed when the spatial peak value does not exceed by 6 dB the average value.
      Below 50 MHz down to 50 Hz, the electric field induces currents flowing along the
      limbs and torso. The current is roughly directly proportional to the electric
      field strength averaged over the body. A convenient way to restrict current
      concentration and hot spots in the neck, ankle and wrist, is to measure the
      current induced in the body. This is not possible for magnetic fields. Instead,
      for a non-uniform magnetic field below 100 kHz the average magnetic flux density
      over the whole body and head are valid exposure indicators to protect the central
      nervous system. The first alternative to analyze exposure to non-sinusoidal
      magnetic fields below 100 kHz is based on the spectral comparison of each
      component to the corresponding reference level. In the second alternative the
      waveform of B or dB/dt is filtered in the time domain with a simple filter, where
      the attenuation varies proportionally to the reference level as a function of
      frequency, and the filtered peak value is compared to the peak reference level
      derived from the ICNIRP reference levels.

PMID- 17495654
TI  - Assessment of non-sinusoidal, pulsed, or intermittent exposure to low frequency
      electric and magnetic fields.
AB  - The correct assessment of non-sinusoidal, pulsed, or intermittent exposure to low
      frequency electric and magnetic fields already is a key issue in the occupational
      environment while becoming more and more important in the domain of the general
      public. The method presented provides a simple and safe solution for the
      assessment of arbitrary field types--including sinusoidal and continuous-wave
      signals--with frequencies up to several 100 kHz and has already proven its
      practicability and usefulness for more than 5 years. The concept is based on
      fundamental laws of physics and electrostimulation and well-established
      physiological data. It allows for a seamless and easy integration in any standard
      or guideline dealing with human safety in electric, magnetic, and electromagnetic
      fields. A very simple-to-use graphical version allows an easy and fast assessment
      of the exposure to non-sinusoidal, pulsed, or intermittent low-frequency magnetic
      fields without introducing a large overestimation of the exposure situation. A
      computer-based version makes a much more detailed signal analysis possible and
      can provide useful information for exposure reduction using modifications of the
      magnetic field's time parameters (e.g., rise/fall times).

PMID- 17495655
TI  - Dosimetric comparison between different quantities for limiting exposure in the
      RF band: rationale and implications for guidelines.
AB  - While source type and its distance from the subject are influential parameters,
      the fundamental exposure metrics are the physically measurable quantities of
      currents, external electric field and magnetic field strengths, and incident
      power density (when appropriate), which induce electric and magnetic fields that
      bring about the interaction of radiofrequency (RF) electromagnetic energy with
      biological systems. Induced fields are the primary cause for biological effect of
      RF exposure, regardless of the mechanism. Thus, in order to achieve a
      quantitative understanding of biological response, the induced electric field and
      the derived dosimetric quantities of specific absorption rate (SAR) and current
      density must be quantified and correlated with the observed phenomenon. In the
      established exposure guidelines, reference levels expressed in terms of physical
      quantities are introduced for practical exposure assessment purposes since the
      basic restrictions are often specified as dosimetric quantities that may be
      impractical to measure. The dosimetric quantity SAR, current density, and their
      determinations are tissue-type dependent and require a region of specific tissue
      mass for averaging. Thus, a smaller averaging region is scientifically more
      relevant and precise. It is emphasized that the sensitivity and resolution of
      present-day computational resources and experimental measurement techniques can
      provide accurate SAR values with a spatial resolution on the order of a 1 mm, in
      dimensions. Furthermore, most exposure guidelines are promulgated on a 4 W kg SAR
      to prevent any whole-body exposure from raising the body temperature to 1 degrees
      C above the norm at 37 degrees C. Special guidance may be needed for higher
      ambient temperature and humidity variations.

PMID- 17495656
TI  - Requirements for reliable worst-case assessment of human exposure to RF
      electromagnetic fields with known uncertainty.
AB  - This paper gives an overview of the current state of science on numerical and
      experimental assessment of the exposure of the human body to radio frequency
      electromagnetic fields. Differences of near- and far-field exposure conditions
      are discussed with respect to the requirements on the correct representation of
      the human body and on the numerical or experimental technique. The general
      requirements for the application of these techniques on the assessment of human
      exposure are defined, and a combined numerical and experimental approach is
      proposed that allows the evaluation of the worst-case absorption considering the
      variability of exposure situations and anatomical properties with known
      uncertainty.

PMID- 17495657
TI  - Implications of clinical RF hyperthermia on protection limits in the RF range.
AB  - The systemic temperature is meticulously regulated to 37-37.5 degrees C. Organ
      systems (skin, digestive system, muscles) have a considerable potential to
      regulate the perfusion for thermal regulation, physical activity, or digestion.
      While the regulation of the systemic temperature (37.5 degrees C) is quite
      strict, the tolerance and regulation potential with respect to local heat is more
      variable. Laboratory studies provided the relationship between thermal doses and
      cytotoxic effects. Tissue damage for short-term expositions (in the range of
      minutes) is only possible for temperatures above 50 degrees C. Radiofrequency
      radiation is utilized in cancer therapy, inducing local tissue temperatures in
      the range of 40-45 degrees C for 30-60 min. During local hyperthermia (with
      heated volumes <1 L) specific absorption rates (SARs) of 100-200 W kg, reactive
      perfusions of 20-40 mL/100 g/min, and tumor temperatures of 42-43 degrees C are
      achieved. Normally no side effects or damage in the normal tissue, such as muscle
      or skin, have been seen. During regional hyperthermia, SARs of 30-40 W kg are
      found in heated volumes of 10 L with temperatures of 41-42 degrees C in tumor
      related measurement points. Then the reactive average perfusion is 6-9 mL/100
      g/min (mean value 8 mL/100 g/min). Local temperatures even for higher SAR are
      regulated to values of not more than 40-42 degrees C. For these temperatures no
      damages in normal tissues have been found after regional hyperthermia in hundreds
      of patients. We conclude that the thermoregulatory potential for the whole body
      or large body regions is limited by the cardiac output, which can at least double
      the output from 5 to 10 L min. Even higher is the potential to compensate in
      smaller volumes. Here the perfusion in muscle can be increased from the basal
      value of 2-4 mL/100 g/min more than 5-10-fold.

PMID- 17495658
TI  - Exposure of biological material to ultra-wideband electromagnetic pulses:
      dosimetric implications.
AB  - Interest in ultra-wideband (UWB) electromagnetic pulses in the communications
      industry and various applications in biotechnology and medicine is constantly
      increasing. While more and more scientific research of bioelectromagnetic
      phenomena is focusing on bioeffects of exposure to non-ionizing UWB pulses,
      characterization of those effects is far from complete. In this paper, a
      synthesis of experimental studies from the point of computational modeling is
      presented. The complexity of the experiments requires a numerical rather than an
      analytical approach. Solving Maxwell's equations using a finite-difference time
      domain (FDTD) method is a necessary step in visualizing and understanding
      broadband response. The advantages of this method include having almost no limits
      in the description of geometrical and dispersive properties of the simulated
      material, numerical robustness, and appropriateness for the computer technology
      of today. Some of the results of the computation and their importance in future
      experimental design are discussed. Improvements in the computational modeling and
      dielectric material description are suggested. This paper aims at justifying a
      scientific basis for UWB exposure safety standards relevant for setting the non
      ionizing UWB radiation exposure guidelines. The results of this research will be
      of interest to people who work with electronic devices involving UWB radiation.

PMID- 17495659
TI  - Static fields: biological effects and mechanisms relevant to exposure limits.
AB  - Recently, the International EMF Project of the World Health Organization (WHO)
      published an Environmental Health Criteria monograph on static electric and
      magnetic fields. In the present paper a short overview is given of the biological
      and health effects discussed in this document. The main conclusions are that no
      acute effects other than transient phenomena such as vertigo and nausea have been
      observed with exposure to static magnetic flux densities up to 8 T. There are no
      reports of long term or chronic adverse effects following prolonged static
      magnetic field exposure, but few data are available on which to base any
      judgment. The guidelines on static field exposure recommended by ICNIRP in 1994
      are discussed in the light of current scientific knowledge.

PMID- 17495660
TI  - Perception of ELF electromagnetic fields: excitation thresholds and inter
      individual variability.
AB  - So far, in guidelines limiting exposure to electromagnetic fields, basic limits
      of intracorporal electric current densities have been recommended to prevent from
      nerve cell stimulation. They were based on experimental data and extrapolated to
      the general population with limited knowledge on the inter-individual
      variability. To assess the variability of cellular excitability the perception
      thresholds for directly applied electric currents were used as surrogate.
      However, until recently, the data on perception ability of electric currents were
      gained from small groups only and led to controversial results, differing by more
      than one order of magnitude. This paper discusses the results of our previous
      research comprising extensive measurements on 1,071 individuals (349 men and 359
      women aging 16 to 60 y, 117 girls and 123 boys aging 9 to 16 years, and 123
      individuals older than 60 y). Their electric current perception thresholds fit
      fairly well with a log-normal distribution. The electric 50 Hz current perception
      threshold was measured by directly applied pairs of electrodes at the lower
      forearms. It was found that the inter-individual variability comprises two orders
      of magnitudes which is one order of magnitude higher than assumed so far. Women
      were found to be significantly more sensitive than men. Depending on the level of
      probability p, the perception threshold for women was 0.77-fold (p = 50%) or even
      0.45-fold (p = 0.5%) lower than for men. Surprisingly, children turned out to be
      considerably more sensitive than men but similar to women. The age dependence
      exhibited a decrease of perception thresholds with age from adult men to boys
      joining the values of girls at ages around 10 y. The results indicate that
      existing safety limits for touch currents need critical review. Apart from the
      inter-individual variability, it was estimated to which place within the
      distribution of perception levels the basic limits were related. Therefore,
      numerical simulations were made to calculate intracorporal electric current
      densities associated with the applied electric currents. The results confirm that
      the basic limits of intracorporal electric current densities as recommended by
      ICNIRP are conservative to prevent cellular excitation.

PMID- 17495661
TI  - A neurobiological basis for ELF guidelines.
AB  - It is well understood that electric currents applied directly to the body can
      stimulate peripheral nerve and muscle tissue; such effects can be fatal if
      breathing is inhibited or ventricular fibrillation is induced. Exposure to
      extremely low frequency electric and magnetic fields will also induce electric
      fields and currents within the body, but these are almost always much lower than
      those that can stimulate peripheral nerve tissue. Guidance on exposure to such
      fields is based on the avoidance of acute effects in the central nervous system.
      This paper reviews the physiological processes involved in nerve cell
      excitability in the peripheral and central nervous system, and the experimental
      evidence for physiologically weak electric field effects. It is concluded that
      the integrative properties of the synapses and neural networks of the central
      nervous system render cognitive function sensitive to the effects of
      physiologically weak electric fields, below the threshold for peripheral nerve
      stimulation. However, the only direct evidence of these weak field interactions
      within the central nervous system is the induction of phosphenes in humans--the
      perception of faint flickering light in the periphery of the visual field, by
      magnetic field exposure. Other tissues are potentially sensitive to induced
      electric fields through effects on voltage-gated ion channels, but the
      sensitivity of these ion channels is likely to be lower than those of nerve and
      muscle cells specialized for rapid electrical signaling. In addition, such
      tissues lack the integrative properties of synapses and neuronal networks that
      render the central nervous system potentially more vulnerable.

PMID- 17495662
TI  - Demodulation in tissue, the relevant parameters and the implications for limiting
      exposure.
AB  - In the biomedical literature there are a number of reports that speculate about
      possible effects in the body due to the demodulation of electromagnetic fields.
      However, only few interactions in amplitude-modulated or even pulse-modulated
      electromagnetic waves are fundamentally plausible and have been demonstrated to
      occur in humans. The following observations fall into this specific category:
      thermal effects of amplitude- or pulse-modulated microwaves; demodulation of
      amplitude- or pulse-modulated electromagnetic waves in cell membranes; and
      demodulation of amplitude- or pulse-modulated electromagnetic fields in the
      electronics of implants such as cardiac pacemakers or cardioverter
      defibrillators. The possible consequences of these effects for the organism,
      their probability of occurrence in everyday life field conditions, and,
      consequently, the implications for limiting exposure are very different.
      Microwave hearing is a harmless effect which is perceived by humans only in
      strong fields with high peak power densities of more than 100 mW cm(-2). In
      normal residential or occupational environments the peak power density of even
      the strongest microwave sources is only around 1 mW cm(-2). Demodulation of pulse
      modulated electromagnetic fields in the cell membranes decreases the stimulation
      threshold of nerves and muscles and can introduce numerous adverse effects
      ranging from perception of pain to dangerous cardiac fibrillations. The
      stimulation and demodulation effects are restricted to carrier frequencies up to
      several MHz. In experiments with 900 and 1,800 MHz packets with lengths of up to
      100 ms and applied powers of up to 100 W, neither a direct stimulation of
      superficial nerves and muscles nor the conditioning of an electrical current
      stimulus could be confirmed. Pulse-modulated electromagnetic waves are
      demodulated in the electronic circuits of implants and can inhibit cardiac
      pacemakers and introduce cardiac arrest in this way. The highest sensitivity
      results from repetition rates of pulses below 100 Hz. The preceding two
      implications should be considered in the elaboration of new general guidelines
      limiting the exposure for healthy as well as for sick persons in the future.

PMID- 17495663
TI  - Thermal mechanisms of interaction of radiofrequency energy with biological
      systems with relevance to exposure guidelines.
AB  - This article reviews thermal mechanisms of interaction between radiofrequency
      (RF) fields and biological systems, focusing on theoretical frameworks that are
      of potential use in setting guidelines for human exposure to RF energy. Several
      classes of thermal mechanisms are reviewed that depend on the temperature
      increase or rate of temperature increase and the relevant dosimetric
      considerations associated with these mechanisms. In addition, attention is drawn
      to possible molecular and physiological reactions that could be induced by
      temperature elevations below 0.1 degrees, which are normal physiological
      responses to heat, and to the so-called microwave auditory effect, which is a
      physiologically trivial effect resulting from thermally-induced acoustic stimuli.
      It is suggested that some reported "nonthermal" effects of RF energy may be
      thermal in nature; also that subtle thermal effects from RF energy exist but have
      no consequence to health or safety. It is proposed that future revisions of
      exposure guidelines make more explicit use of thermal models and empirical data
      on thermal effects in quantifying potential hazards of RF fields.

PMID- 17495664
TI  - Hearing of microwave pulses by humans and animals: effects, mechanism, and
      thresholds.
AB  - The hearing of microwave pulses is a unique exception to the airborne or bone
      conducted sound energy normally encountered in human auditory perception. The
      hearing apparatus commonly responds to airborne or bone-conducted acoustic or
      sound pressure waves in the audible frequency range. But the hearing of microwave
      pulses involves electromagnetic waves whose frequency ranges from hundreds of MHz
      to tens of GHz. Since electromagnetic waves (e.g., light) are seen but not heard,
      the report of auditory perception of microwave pulses was at once astonishing and
      intriguing. Moreover, it stood in sharp contrast to the responses associated with
      continuous-wave microwave radiation. Experimental and theoretical studies have
      shown that the microwave auditory phenomenon does not arise from an interaction
      of microwave pulses directly with the auditory nerves or neurons along the
      auditory neurophysiological pathways of the central nervous system. Instead, the
      microwave pulse, upon absorption by soft tissues in the head, launches a
      thermoelastic wave of acoustic pressure that travels by bone conduction to the
      inner ear. There, it activates the cochlear receptors via the same process
      involved for normal hearing. Aside from tissue heating, microwave auditory effect
      is the most widely accepted biological effect of microwave radiation with a known
      mechanism of interaction: the thermoelastic theory. The phenomenon, mechanism,
      power requirement, pressure amplitude, and auditory thresholds of microwave
      hearing are discussed in this paper. A specific emphasis is placed on human
      exposures to wireless communication fields and magnetic resonance imaging (MRI)
      coils.

PMID- 17495665
TI  - Effects of exposure of animals to ultra-wideband pulses.
AB  - Publications reporting biological effects of whole-animal exposures to ultra
      wideband (UWB) pulses are reviewed. Conditions and results of the published
      studies are grouped by type of exposure: free-field, parallel-plate transmission
      line, and giga transverse electromagnetic cell (GTEM). The studies investigated
      the cardiovascular system, the nervous system, teratology, tumor production, and
      genotoxicity in different experimental animals, primarily rodents. Depending on
      the study, pulses had peak electric fields of 10 to 250 kV m(-1), durations of
      0.8 to 8 ns, and rise times between 140 and 340 ps. In most cases only small,
      sometimes spurious, differences between exposed and nonexposed animals were seen.
      Effects on interaction with an inhibitor of nitric oxide synthase and on long
      term blood pressure were statistically significant in the studies reviewed.

PMID- 17495666
TI  - A comparison of important international and national standards for limiting
      exposure to EMF including the scientific rationale.
AB  - A comparison of Eastern (from Russia, Hungary, Bulgaria, Poland, and the Czech
      Republic) and Western (represented by the International Commission on Non
      Ionizing Radiation Protection guidelines and the Institute of Electrical and
      Electronic Engineers standards) radiofrequency standards reveals key differences.
      The Eastern approach is to protect against non-thermal effects caused by chronic
      exposure to low level exposure, and the occupational basic restriction is power
      load (the product of intensity and exposure duration). In contrast, the Western
      approach is to protect against established acute biological effects that could
      signal an adverse health effect, and the principal basic restriction is the
      specific absorption rate to protect against thermal effects. All of the standards
      are science-based, but a fundamental difference arises from a lack of agreement
      on the composition of the reference scientific database and of which adverse
      effect needs to be protected against. However, differences also exist between the
      ICNIRP and IEEE standards. An additional complication arises when standards are
      derived or modified using a precautionary approach. For ELF the differences
      between ICNIRP and IEEE are more fundamental; namely, differences in the basic
      restriction used (induced current; in-situ electric field) and the location of
      breakpoints in the strength-frequency curves result in large differences. In
      2006, ICNIRP will initiate the review of their ELF and radiofrequency guidelines,
      and this will provide an opportunity to address differences in standards and the
      move towards harmonization of EMF standards and guidelines.

PMID- 17495667
TI  - Implications from epidemiologic studies on magnetic fields and the risk of
      childhood leukemia on protection guidelines.
AB  - The objective of this review is to discuss the impact of findings in
      epidemiological studies on magnetic fields and the risk of childhood leukemia on
      the definition of exposure limits. A large number of epidemiological studies have
      consistently shown an association between the risk of childhood leukemia and
      residential extremely low-frequency magnetic field exposures. There is virtually
      no supportive data from experimental research and, so far, no proposed
      explanation has reached a level beyond speculation. The contradictory results
      from epidemiological and experimental research may either be due to
      methodological limitations creating a spurious association in the epidemiological
      studies or to a failure of experimental research to examine mechanisms relevant
      in the complex origin of childhood leukemia. Taking this together, the overall
      evidence is not strong enough to demand a revision of the current guidelines for
      public protection. Application of precautionary measures may be an option;
      however, decision-makers should be advised that these measures are often not
      straightforward and a careful evaluation of a possible benefit needs to be
      performed for each individual situation. Undoubtedly there are gaps in research,
      and no substantial contribution for clarification of the apparent inconsistencies
      emerges from recent studies. However, there are important lessons to learn,
      either with respect to the etiology of childhood leukemia or with respect to the
      need for improving epidemiological methods for the identification of presumably
      weak associations.

PMID- 17495668
TI  - Accounting for human variability and sensitivity in setting standards for
      electromagnetic fields.
AB  - Biological sensitivity and variability are key issues for risk assessment and
      standard setting. Variability encompasses general inter-individual variations in
      population responses, while sensitivity relates to unusual or extreme responses
      based on genetic, congenital, medical, or environmental conditions. For risk
      assessment and standard setting, these factors affect estimates of thresholds for
      effects and dose-response relationships and inform efforts to protect the more
      sensitive members of the population, not just the typical or average person.
      While issues of variability and sensitivity can be addressed by experimental and
      clinical studies of electromagnetic fields, investigators have paid little
      attention to these important issues. This paper provides examples that illustrate
      how default assumptions regarding variability can be incorporated into estimates
      of 60-Hz magnetic field exposures with no risk of cardiac stimulation and how
      population thresholds and variability of peripheral nerve stimulation responses
      at 60-Hz can be estimated from studies of pulsed gradient magnetic fields in
      magnetic resonance imaging studies. In the setting of standards for
      radiofrequency exposures, the International Commission for Non-Ionizing Radiation
      Protection uses inter-individual differences in thermal sensitivity as one of the
      considerations in the development of "safety factors." However, neither the range
      of sensitivity nor the sufficiency or excess of the 10-fold and the additional 5
      fold safety factors have been assessed quantitatively. Data on the range of
      responses between median and sensitive individuals regarding heat stress and
      cognitive function should be evaluated to inform a reassessment of these safety
      factors and to identify data gaps.

PMID- 17495669
TI  - Rapporteur Report: ICNIRP international workshop on EMF dosimetry and biophysical
      aspects relevant to setting exposure guidelines.
AB  - The International Commission on Non-Ionizing Radiation Protection has commenced
      the revision of its EMF guidelines in the frequency range up to 300 GHz. The
      ICNIRP International EMF Dosimetry Workshop has brought together a range of
      scientists to discuss the basis of the existing guidelines and to highlight those
      areas where attention needs to be given. This report is an attempt to extract the
      key messages from each of the presentations. A tabulation of the important issues
      discussed in the summary and conclusion session is provided at the end of this
      report.

PMID- 17495670
TI  - On absorbed dose coefficients calculated by Veinot and Hertel.

PMID- 17495676
TI  - The influence of cost containment strategies and physicians' financial
      arrangements on patients' trust and satisfaction.
AB  - Concerns have been raised about the potential for negative effects of health
      plans' cost containment strategies on the patient-physician relationship. We
      surveyed Minnesota patients with diabetes or hypertension (N = 595) and their
      physicians (N = 389) to assess the associations of gatekeeping, utilization
      profiling, and financial arrangements with patients' trust in and satisfaction
      with their physician. We found that patients of physicians exposed to various
      cost containment strategies were generally not less trusting in or less satisfied
      with their physicians than other patients. These results suggest that physicians
      may have managed potential conflicts to avoid compromising the patient-physician
      relationship.

PMID- 17495677
TI  - Developing a culture of safety in ambulatory care settings.
AB  - The focus on medical error prevention has prompted forward-thinking healthcare
      providers to increasingly support an organizational culture that supports and
      promotes patient safety. A culture of safety is necessary before other patient
      safety practices can be introduced successfully. Various elements of a culture of
      safety are discussed. Some organizations have implemented survey tools to assess
      their safety culture. Assessing an organization's culture of safety is just the
      beginning. Setting priorities for action and identifying strategies to improve
      healthcare safety must follow with support of the organization's leaders and
      frontline staff. Recommendations for action are provided.

PMID- 17495678
TI  - Risk management tips for ambulatory surgery centers.
AB  - As the number of complex procedures performed in ambulatory surgery centers
      continues to increase, facilities should ensure periodic review of their
      strategies to ensure patient safety and minimize risks. Several measures ranging
      from proper patient selection to an effective informed consent process to a
      comprehensive credentialing program are key strategies to reducing risks to
      patients and managing patient expectations.

PMID- 17495679
TI  - Standardize concepts, not tools for quality improvement.
AB  - Pay for performance has become a new mantra in the ongoing efforts to improve the
      quality of healthcare and stabilize healthcare costs. In response to complaints
      of employers and others, numerous organizations have emerged to try and
      standardize the tools used to measure quality. This article maintains that such
      an approach will not lead to improvement in quality. Rather, we should be
      standardizing on specific quality of care concepts, such as hospital satisfaction
      or bypass graft mortality. In turn, appropriate federal agencies should calibrate
      (or translate) well-validated tools measuring desired concepts. This would allow
      consumers to take action on quality reports calibrated to allow comparison of
      results based on a standardized concept such as hospital satisfaction but which
      in turn contains results using different, well-validated satisfaction
      questionnaires. This article provides a road map for the implementation of a
      process of standardizing on concepts rather than tools.

PMID- 17495680
TI  - Empowerment.
AB  - The term "empowerment" has different meanings in different sociocultural and
      political contexts. Broadly speaking, empowerment refers to the expansion of
      assets and capabilities of poor people to participate in, negotiate with,
      influence, control, and hold accountable institutions that affect people's lives.
      The paper explores each of these aspects and identifies access to information,
      inclusion and participation, accountability, and local organizational capacity as
      the four main elements of empowerment. These elements are closely intertwined and
      act in synergy, in order to create more effective, responsive, inclusive, and
      accountable institutions. The paper also highlights the crucial role empowerment
      plays in providing access to basic services and improved local and national
      governance. This will enable poor people to develop their own capabilities,
      increase their assets, and move out of poverty.

PMID- 17495681
TI  - The emerging role of cell phone technology in ambulatory care.
AB  - Three factors are coinciding to reshape the ambulatory care market: chronic
      disease prevalence, workforce shortages, and the availability of cell phone
      technology with very high consumer penetration. These factors will
      disproportionately drive the business strategies and practices of ambulatory care
      providers, payers, and delivery systems this decade. Market dynamics are driving
      the healthcare industry to adopt new strategies to deal with the swelling
      prevalence of chronic disease. Healthcare organizations are constrained by money
      and inadequate tools to systematically manage chronic care patients. As a result,
      traditional notions of ambulatory care are changing from being provider-centered
      to becoming more patient-centric. A host of new remote monitoring and
      communication technologies are available so that providers can now interact with
      patients "anywhere, anytime." The traditional care setting is shifting to where
      the patient is rather than where the physician is located. Patients are the most
      underutilized resource in healthcare, and patient engagement is the key to
      managing chronic illness. Cell phones are particularly suited for leveraging the
      time and expertise of providers while engaging patients in their own self-care.
      To demonstrate this concept, data are presented that illustrate how cell phone
      applications significantly reduced the cost of treating severely asthmatic
      children and teens in 2 ways: through more frequent communication between
      patients and their medical teams, and by motivating patients to become more
      engaged and knowledgeable about their care. The healthcare industry can support
      consumer choice by making available as many options as possible for engaging
      patients in their care. Consumers like having choices and patients are no
      different: they are not all one type. This suggests an emerging role for cell
      phone applications and platforms that enable both Internet and medical device
      connectivity where appropriate for managing chronic conditions. As a management
      tool, cell phones have the potential to become a standard of care in the field.
      If so, cell phones may materially offset the cost of chronicity by helping
      patients avoid preventable events of care in licensed health facilities,
      something much more economically powerful than attempting to reduce the costs of
      producing care in those settings.

PMID- 17495682
TI  - Extremely obese patients in the healthcare setting: patient and staff safety.
AB  - As a growing number of people in the United States are classified as overweight
      or obese, healthcare facilities and practices are considering ways to address the
      needs of this population. Issues to be addressed include facility construction,
      equipment selection, availability of certain supplies, staff sensitivity, and
      staff training and education in appropriate patient lifting. The ever-increasing
      prevalence of obesity in the US population makes implementing these features a
      valuable long-term investment and significantly reduces the risk of injury to
      patients and staff.

PMID- 17495683
TI  - Disparities in perceptions of healthcare access in a community sample.
AB  - Disparities in health status persist for many sociodemographic groups in the
      United States. An understanding of barriers to healthcare access and utilization
      can assist community-based initiatives in developing strategies to improve the
      health of minority and low-income populations. Using self-reported information
      from 3014 community residents, a factor analysis was conducted that defined
      barriers to healthcare by 4 dimensions: (1) time and competing priorities, (2)
      convenience and availability, (3) healthcare utilization, and (4) healthcare
      affordability. Differential effects of demographics were observed on all factors.
      Racial disparities were found where African Americans experienced more problems
      based on the convenience and availability of services (P < .02) than did whites,
      after controlling for income, education, age, and marital status. In addition,
      gender differences showed that women experienced greater difficulty with time and
      competing priorities than men (P < .001); however, women experienced fewer
      problems related to utilization (P < .001). Of the covariates, income was
      significant (P < .01) on 3 of the 4 indicators. This study points to the need to
      develop interventions that address the unique challenges faced by different
      population groups to ensure timely healthcare. In addition, the reduction of
      economic disparities should be considered as an important strategy to improve
      public health.

PMID- 17495684
TI  - Disparities in smoking: data from the Nashville REACH 2010 project.
AB  - The Nashville REACH 2010 project is funded by the Centers for Disease Control and
      Prevention to reduce health disparities in diabetes and heart disease among
      African Americans in Nashville, Tenn. While Tennessee has the third highest
      smoking rate (26.1%) in the United States, there are few appropriate local data
      useful for planning and evaluating local antismoking interventions. Data gathered
      for Nashville REACH 2010 from 4 large random telephone surveys were pooled to
      produce a database (n = 15,076) to define the extent of the local smoking
      disparity and the subgroups with the highest and lowest prevalence of smoking.
      African American women were least likely to smoke (21.3%) followed by white women
      (24.9%), and then African American and white men (27.3% and 27.9%, respectively).
      Among African American subgroups, smoking was lowest in students (10.8%) and
      retirees (17.1%) and highest in unemployed men (45.9%). In a logistic regression,
      smoking was highest among single men, the lowest educational level, the
      unemployed, the lowest income groups, and those between 40 and 50 years of age.

PMID- 17495685
TI  - The role of community health centers in delivering primary care to the
      underserved: experiences of the uninsured and Medicaid insured.
AB  - Community health centers (CHCs) have long served an important safety-net
      healthcare delivery role for vulnerable populations. Federal efforts to expand
      CHCs, while potentially reducing the Federal budget for Medicaid, raise concern
      about how Medicaid and uninsured patients of CHCs will continue to fare. To
      examine the primary care experiences of uninsured and Medicaid CHC patients and
      compare their experiences with those of similar patients nationally, cross
      sectional analyses of the 2002 CHC User Survey with comparison data from the 1998
      and 2002 National Health Interview surveys were done. Self-reported measures of
      primary care access, longitudinality, and comprehensiveness of care among adults
      aged 18 to 64 years were used. Despite poorer health, CHCs were positively
      associated with better primary care experiences in comparison with similar
      patients nationally. Uninsured CHC patients were more likely than similar
      patients nationally to report a generalist physician visit in the past year (82%
      vs 68%, P < .001), having a regular source of care (96% vs 60%, P < .001),
      receiving a mammogram in the past 2 years (69% vs 49%, P < .001), and receiving
      counseling on exercise (68% vs 48%, P < .001). Similar results were found for CHC
      Medicaid patients versus Medicaid patients nationally. Even within CHCs, however,
      Medicaid patients tended to report better primary care experiences than the
      uninsured. Health centers appear to fill an important gap in primary care for
      Medicaid and uninsured patients. Nonetheless, this study suggests that Medicaid
      insurance remains fundamental to accessing high-quality primary care, even within
      CHCs.

PMID- 17495687
TI  - Women's rights--a case study of Palestinian Arabs.

PMID- 17495688
TI  - Occupational asthma due to welding fumes from stellite.

PMID- 17495689
TI  - Health and exposure concerns of veterans deployed to Iraq and Afghanistan.
AB  - OBJECTIVE: We report the clinical concerns of US veterans of Operations Iraqi
      Freedom and Enduring Freedom evaluated at the New Jersey War-Related Illness and
      Injury Study Center (NJ WRIISC) between June 2004 and January 2006. METHODS: We
      conducted a retrospective chart review of veterans' health and exposure concerns.
      RESULTS: Veterans (n=56) reported an average of 4 (standard deviation [SD] = 2.1;
      range, 0-9) physical health concerns, and 2.7 (SD=2.3; range, 0-10) exposure
      concerns. The majority of veterans (55%) had a mental health concern, most
      commonly, posttraumatic stress disorder. The most common exposure concerns were
      depleted uranium, multiple vaccinations, and poor air quality. Greater
      proportions of Reserve veterans reported genitourinary concerns and exposure to
      smoke from burning trash than active duty veterans. CONCLUSIONS: Veterans of
      military operations in Southwest Asia have deployment-related health and exposure
      concerns that will need to be addressed by their ambulatory care physicians.

PMID- 17495690
TI  - Prevalence of cardiovascular risk factors in middle-aged type 2 diabetic
      automobile employees assessed at the workplace--the Praeford study.
AB  - OBJECTIVE: The purpose of this study was to provide contemporary data on the
      prevalence of cardiovascular risk factors in middle-aged diabetic employees in
      Germany. METHODS: Cardiovascular risk factors were assessed at the workplace in
      employees of the automobile industry who identified themselves as having type 2
      diabetes mellitus. The proportion of subjects reaching the target values for
      hemoglobin A1c (HbA1c), systolic blood pressure, and low-density lipoprotein
      (LDL) cholesterol was analyzed. RESULTS: Among 4234 employees, 91 employees with
      diabetes were identified (mean age, 52 years). Only 7 of 91 (8%) diabetic
      employees achieved all three recommended target values. Blood pressure targets
      were achieved by 26%, HbA1c target value by 54%, and LDL target value by 31% of
      employees. CONCLUSION: Only a negligible proportion of working people with
      diabetes achieve the recommended target values. This sobering result questions
      current management modalities and calls for new treatment and monitoring
      strategies for working people with diabetes.

PMID- 17495691
TI  - Hypertension and road traffic noise exposure.
AB  - OBJECTIVE: The purpose of this study was to assess the relationship between road
      traffic noise exposure at home and the prevalence of hypertension. METHODS: We
      conducted cross-sectional analyses in a large random sample (N=40,856) of
      inhabitants of Groningen City, and in a subsample (the Prevention of Renal and
      Vascular End-Stage Disease [PREVEND]) study cohort; N=8592). RESULTS: Before
      adjustment for confounders, road traffic noise exposure was associated with self
      reported use of antihypertensive medication in the city of Groningen sample (odds
      ratio [OR]=1.31 per 10-dB increase in Lden). Adjusted odds ratios were
      significant for the subjects between 45 and 55 years old in the full model when
      adjusted for PM10 (OR=1.19) and at higher exposure (Lden >55 dB) only (OR=1.21;
      with adjustment for PM10, OR=1.31). In the PREVEND cohort, the unadjusted odds
      ratio was 1.35 for hypertension (systolic and diastolic blood pressure >140 and
      >90 mm Hg, respectively, or use of antihypertensive medication). Again, the
      adjusted odds ratio was significant for subjects between 45 and 55 years old
      (OR=1.27; with adjustment for PM10, OR=1.39). CONCLUSIONS: Exposure to road
      traffic noise may be associated with hypertension in subjects who are between 45
      and 55 years old. Associations seemed to be stronger at higher noise levels.

PMID- 17495692
TI  - The direct and indirect cost burden of clinically significant and symptomatic
      uterine fibroids.
AB  - OBJECTIVE: To estimate direct medical costs and indirect (productivity related)
      for women age 25 to 54 who had clinically significant and symptomatic uterine
      fibroids (UF). METHODS: We compared direct medical expenditures among 30,659
      women who had clinically significant and symptomatic UF to expenditures among an
      equal number of matched controls who did not. We also compared indirect costs for
      a sub-sample of 910 employed women in each group. Regression analyses controlled
      for demographic and casemix factors. RESULTS: Mean 12-month direct medical costs
      for women with UF were $11,720 versus $3257 for controls, and mean 12-month
      indirect costs for women with UF were $11,752 versus $8083 for controls.
      Differences were statistically significant (P<0.0001). CONCLUSIONS: UF is a
      costly disorder and merits thought as interventions are considered to improve
      women's health and productivity.

PMID- 17495693
TI  - Pregnancy protection program in a large chemical company: design and initial
      survey results.
AB  - OBJECTIVES: To describe the BASF pregnancy protection program and provide initial
      results regarding selected pregnancy outcomes. METHODS: Pregnancies (n=1148)
      occurring between 1997 and 2002 were identified and outcomes were documented by
      questionnaires administered after the pregnancy announcement, end of pregnancy,
      and one year later. Potential maternal exposures were assessed via job histories,
      workplace inspections, and questionnaire. RESULTS: Participation was 90% overall
      and was consistently high across employee subgroups. Pregnancy losses (11.5%) did
      not differ significantly by type of work. Among pregnancy symptoms vaginal
      bleeding was weakly associated with two exposure measures. Preterm births (8.7%)
      were in agreement with general population norms and did not vary by maternal
      exposure category. CONCLUSIONS: High participation rates and a structured
      approach to employee education and documentation of reproductive outcomes may be
      of value in addressing reproductive health issues in the workplace.

PMID- 17495694
TI  - Pregnancy protection program in a large chemical company: infant outcomes.
AB  - OBJECTIVES: The purpose of this study was to investigate reproductive outcomes in
      infants relative to maternal exposures in the chemical industry. METHODS: Via
      questionnaires administered after the pregnancy announcement, end of pregnancy,
      and 1 year later, infant outcomes were documented for 1147 live births. Maternal
      exposure factors were evaluated relative to birth height and weight, sex ratio,
      Apgar score at 5 minutes, and major malformations. RESULTS: Birth height and
      weight, sex ratio, and Apgar score did not differ by maternal work area or
      chemical hazard categories. Major malformations (3.1%) and organ-specific
      anomalies were consistent with the experience of a regional birth defects
      registry. Rates of malformation were marginally higher in infants born to women
      assigned to chemical versus office jobs. CONCLUSIONS: Infant outcomes to date
      have been consistent with comparable findings from population-based studies.
      Longer-term observation will be needed to assess trends for low-frequency
      outcomes and more specific maternal exposures.

PMID- 17495695
TI  - General mortality from 1944 through 1994 for a silicon-based chemical company.
AB  - The objective of this study is to reevaluate the statistically significant
      elevated risk of lung cancer among men with >or=20 years of employment at Dow
      Corning Corporation, a manufacturer of silicon-based materials. The cohort
      included 712 deaths among 8266 employees who were hired from 1943 to 1992 with
      follow-up through 1994. Standardized mortality ratios (SMRs) were calculated for
      63 causes of death. Analysis confirmed a statistically significant increased
      mortality from cancer of the bronchus, trachea, and lung among men, prior to
      1985, who jointly classified with >or=30 years of work duration and >or=30 years
      since first employed. SMRs for lung cancer after 1985, however, were not
      statistically significant and were inconsistent across work duration and years
      since first employed intervals. The study provides no evidence for elevated
      mortality among Dow Corning workers since the 1991 cohort mortality study. This
      study describes the updated mortality experience of a large employee cohort from
      a major silicon-based manufacturer. It illustrates that a well-designed mortality
      study can be a key component of employee health surveillance efforts in an
      industrial setting with potential hazardous workplace exposures.

PMID- 17495696
TI  - Estimating the cosmic radiation dose for a cabin crew with flight timetables.
AB  - OBJECTIVE: Because of the lack of recorded flight history for cabin crew, a
      retrospective assessment of exposure to cosmic radiation is complicated. Our aim
      was to develop an assessment method for occupational exposure based on flight
      timetables. METHODS: The frequency of flights, aircraft types, and flight
      profiles from timetables were collected. The cosmic radiation dose was calculated
      with the EPCARD software. Based on annual doses and work history, the cumulative
      dose was estimated. RESULTS: The annual dose increased linearly: 0.7 milliSievert
      (mSv) in 1960, 1.6 mSv in 1980, 2.3 mSv in 1985, and 2.1 mSv in 1995. The median
      cumulative dose was 20.8 mSv (minimum 0.4 mSv, maximum 61.6 mSv). CONCLUSIONS:
      This method provides a simple algorithm for occupational dose assessment for
      cabin crew and can be used in other research settings as well.

PMID- 17495697
TI  - A 26-year cohort mortality study of French construction workers aged 20 to 64
      years.
AB  - OBJECTIVE: The purpose of this report was to study the cause-specific mortality
      of French workers in the construction industry. METHODS: From a cohort of 12,788
      male workers, standardized mortality ratios (SMRs) and 95% confidence intervals
      (CI) were calculated for the years between 1974 and 1999 for workers aged 20 to
      64 years. RESULTS: All-cause mortality was significantly increased (SMR=111,
      CI=106-206). Excess mortality was found for cancers (SMR=125, CI=117-134),
      especially for the oral cavity and pharynx (SMR=134, CI=108-163), digestive
      (SMR=120, CI=104-137) and respiratory (SMR=143, CI=128-159) systems;
      cerebrovascular disease (SMR=130, CI=106-158); diseases of the digestive system
      (SMR=130, CI=113-149), and accidental falls (SMR=158, CI=105-125). Excess risks
      were limited to blue-collar workers. CONCLUSIONS: Despite a probable role of
      lifestyle and potential limitations of the study, elevated mortality was observed
      for several causes possibly related to occupational factors.

PMID- 17495698
TI  - A 56-year mortality follow-up of Texas petroleum refinery and chemical employees,
      1948-2003.
AB  - OBJECTIVE: To further investigate the mortality risk of employees who worked in
      the petroleum refinery industry, we updated an earlier investigation by extending
      the mortality follow-up by an additional 14 years through 2003. METHODS: The
      cohort consisted of 10,621 employees with an average follow-up of 34 years. We
      used the standardized mortality ratio (SMR) adjusted for age, race, and calendar
      years as a measure of risk. RESULTS: Overall mortality (SMR=0.77, 95% confidence
      interval [CI], 0.74-0.79), all cancer mortality (SMR=0.87, 95% CI=0.82-0.93), and
      most cause-specific mortalities for the total study population were lower than or
      similar to that of the population of Harris County, Texas. This study did not
      show a significant increase in leukemia in the total population or in any of the
      subgroups. The only statistically significant excess of mortality found in this
      study was an increase in mesothelioma among maintenance employees; the SMR was
      4.78 (95% CI=2.54-8.17) among employees who worked for a minimum of one year and
      was 7.51 (95% CI=3.75-13.45) among those with 10 or more years of employment and
      20 or more years of latency. CONCLUSIONS: After more than half a century of
      follow-up, employees at this facility continue to show more favorable mortality
      outcomes than the general local population. Overall, no statistically significant
      increase of leukemia or of any of the specific cell types was found. The
      increased mesothelioma is likely related to past exposure to asbestos.

PMID- 17495699
TI  - Health complaints and satisfied with the job? A cross-sectional study on work
      environment, job satisfaction, and subjective health complaints.
AB  - OBJECTIVE: The aim of this study was to examine the prevalence of subjective
      health complaints (SHCs) among satisfied and dissatisfied workers. The second aim
      was to evaluate whether any SHC differences were attributable directly to the
      work environment or mediated by the individual perception of the environment
      (satisfactory or not). METHOD: In a cross-sectional study of 458 employees (56%
      women) in 5 different organizations, work environment, job satisfaction, and SHC
      were measured. RESULTS: Satisfied workers reported an average of five to six
      subjective health complaints that correspond to the prevalence found in a
      Norwegian general population. Work environment explained 43% of the variance for
      job satisfaction and 9% of the variance in SHCs. CONCLUSION: SHCs are common
      among satisfied workers. Work environment has only a limited influence on this
      validated health indicator.

PMID- 17495701
TI  - Can the concept of environmental public health tracking work in a real-life
      setting?

PMID- 17495700
TI  - Chronic bronchitis among nonsmoking farm women in the agricultural health study.
AB  - OBJECTIVE: The purpose of this study was to examine agricultural risk factors for
      chronic bronchitis among nonsmoking farm women. METHODS: We used self-reported
      enrollment data from the 21,541 nonsmoking women in the Agricultural Health Study
      to evaluate occupational risk factors for prevalent chronic bronchitis among farm
      women. Odds ratios (ORs) for chronic bronchitis for occupational exposures were
      adjusted for age, state, and related agricultural exposures. RESULTS: Applying
      manure and driving combines were independently associated with chronic
      bronchitis. Off-farm job exposures associated with chronic bronchitis were
      organic dusts, asbestos, gasoline, and solvents. Five pesticides were associated
      with chronic bronchitis after multivariate adjustment and sensitivity analyses:
      dichlorvos (OR=1.63, 95% CI=1.01, 2.61), DDT (OR=1.67, 95% CI=1.13, 2.47),
      cyanazine (OR=1.88, 95% CI=1.00, 3.54), paraquat (OR=1.91, 95% CI=1.02, 3.55),
      and methyl bromide (OR=1.82, 95% CI=1.02, 3.24). CONCLUSION: Pesticides as well
      as grain and dust exposures were associated with chronic bronchitis among
      nonsmoking farm women.

PMID- 17495705
TI  - Dalteparin versus enoxaparin for venous thromboembolism prophylaxis in acute
      spinal cord injury and major orthopedic trauma patients: 'DETECT' trial.
AB  - BACKGROUND: To compare the impact of switching from enoxaparin 30 mg
      subcutaneously (SC) twice daily to dalteparin 5,000 units SC once daily for
      venous thromboembolism (VTE) prophylaxis in critically-ill major orthopedic
      trauma and/or acute spinal cord injury (SCI) patients. METHODS: DETECT was a
      retrospective, cohort study at a tertiary care referral teaching center-phase 1
      from December 1, 2002 to November 30, 2003 (enoxaparin); and phase 2 from January
      1, 2004 to December 31, 2004 (dalteparin). Major orthopedic trauma patients with
      pelvic, femoral shaft, or complex lower extremity fractures, and/or acute SCI
      patients admitted to the intensive care unit and who received a low-molecular
      weight heparin (LMWH) for VTE prophylaxis were included. RESULTS: DETECT reviewed
      135 patients (63 enoxaparin, 72 dalteparin), with similar baseline demographics,
      clinical characteristics, injuries, severity of illness, and risk factors for
      VTE. Clinically symptomatic proximal deep vein thrombosis (DVT) or pulmonary
      embolism (PE) rates were 1.6% with enoxaparin and 9.7% with dalteparin (p=0.103,
      absolute risk increase [ARI] of 8.1% [-0.6% to 15.6%]), with no differences in
      major bleeding (6.4% versus 6.9%) or minor bleeding (64% versus 69%), or
      mortality (4.8% versus 6.9%). Switching from enoxaparin to dalteparin was
      associated with $12,485 (CAD) in LMWH acquisition cost savings. CONCLUSIONS:
      DETECT raises the hypothesis that dalteparin 5,000 units SC daily may not be
      clinically noninferior to enoxaparin 30 mg SC twice daily for VTE prophylaxis in
      this high-risk population. Until an adequately-powered, prospective
      noninferiority trial is performed, enoxaparin is supported by level 1 evidence
      and should be the prophylactic agent of choice.

PMID- 17495706
TI  - Coagulation and complement protein differences between septic and uninfected
      systemic inflammatory response syndrome patients.
AB  - BACKGROUND: Systemic inflammatory response syndrome (SIRS) represents a host
      response to various insults. Recent advances have demonstrated an interconnection
      between inflammation, complement, and coagulation. This experiment was designed
      to evaluate differences in plasma protein profiles between clinically identical
      patients: septic versus uninfected SIRS patients, prior to clinical diagnosis of
      infection. METHODS: Patients admitted to an intensive care unit of a major
      university, meeting two of four SIRS criteria were followed prospectively for
      development of sepsis. Plasma samples were collected daily and divided into two
      groups: a preseptic group that subsequently developed sepsis and a SIRS group
      that remained uninfected. Protein profiling was accomplished by three-dimensional
      liquid chromatography fractionation with electrospray ion trap mass spectrometry
      after immunodepletion of abundant proteins and a trypsin digest. Spectra peaks
      were identified using Agilent Technologies Spectrum Mill Workbench software.
      Relevance to biologic pathways was analyzed and statistical significance
      determined with DAVID 2.1 available at the National Institutes of Health.
      RESULTS: A total of 134 unique proteins were significantly different between
      groups. Thirty-two of these (23.5%) mapped to the complement and coagulation
      cascade (KEGG), 10 (7.5%) mapped to classic complement pathway; 11 (8.2%) mapped
      to complement pathway, and 8 (6.0%) mapped to lectin binding complement pathway
      (Biocarta). These pathways were all significantly (p<0.0001) over-represented in
      sepsis patients compared to SIRS-only patients. CONCLUSION: Using novel mass
      spectrometry methodology, we were able to demonstrate differential protein
      profiles in septic versus uninfected SIRS patients prior to clinical diagnosis of
      sepsis.

PMID- 17495707
TI  - Early versus late recombinant factor VIIa in combat trauma patients requiring
      massive transfusion.
AB  - BACKGROUND: Coagulopathy is a consequence of severe trauma, especially in
      massively transfused patients (>or=10 units of red blood cells in 24 hours), and
      is associated with increased mortality. We hypothesized that recombinant factor
      VIIa (rFVIIa) administered to massive transfusion patients before transfusion of
      8 units of blood (early) would reduce transfusion requirements compared with
      rFVIIa after 8 units (late). METHODS: We retrospectively reviewed records for
      trauma admissions to combat support hospitals in Iraq between January 2004 and
      October 2005. Patients requiring a massive transfusion and receiving rFVIIa were
      identified. Groups were divided into those who received rFVIIa early or late.
      RESULTS: Of 5,334 trauma patients (civilian and military), 365 (6.8%) required
      massive transfusion. Of these, 117 (32%) received rFVIIa. Complete records for
      blood transfusions were available for 61 patients: 90% had penetrating trauma, 17
      received rFVIIa early, and 44 received it late. At admission, temperature, heart
      rate, blood pressure, Glasgow Coma Scale score, base deficit, hemoglobin,
      platelets, prothrombin time/International Normalized Ratio, and Injury Severity
      Score were similar in both groups as were administered units of fresh frozen
      plasma, fresh whole blood, cryoprecipitate (cryo), and crystalloid. The early
      rFVIIa group required fewer units of blood during the first 24-hour period (mean
      20.6 vs. 25.7, p=0.048) and fewer units of stored red blood cells (mean 16.7 vs.
      21.7, p=0.049). Early and late mortality (33.3% vs. 34.2%, p=NS), acute
      respiratory distress syndrome (5.9 vs. 6.8%, p=NS), infection (5.9% vs. 9.1%,
      p=NS), and thrombotic events (0% vs. 2.3%, p=NS) were similar. CONCLUSIONS: Early
      administration of rFVIIa decreased red blood cell use by 20% in trauma patients
      requiring massive transfusion.

PMID- 17495708
TI  - A controlled trial of brief intervention versus brief advice for at-risk drinking
      trauma center patients.
AB  - BACKGROUND: Numerous reports document that preinjury alcohol use is associated
      with all modes of injury requiring treatment in a trauma center, with 25% to 50%
      or more of patients testing positive for alcohol at the time of admission. There
      is evidence that in trauma patients unaddressed alcohol use problems result in
      recurrent injury requiring readmission to a trauma center and/or death. METHODS:
      A randomized clinical trial was conducted to assess the effectiveness of two
      types of brief interventions to reduce drinking and the consequences of drinking.
      Trauma patients defined as at-risk alcohol users (n=497) were randomized into two
      treatment options: a brief personalized motivational intervention (PMI), or brief
      information and advice (BIA). After a brief assessment, PMI subjects received a
      motivational session, feedback letter, and two postdischarge telephone contacts,
      whereas the BIA group received a brochure and one postdischarge telephone
      contact. Both groups were reassessed at 6 and 12 months postinjury. RESULTS: Both
      the PMI and BIA groups had statistically significant reductions in drinking,
      binge episodes, and consequences related to drinking that persisted from the 6-
      to the 12-month follow-up. However, although not statistically significant, for
      those classified as lower-level drinkers (<or=1 drink per day), there was a
      consistent pattern of maintaining reductions for the PMI group at 12 months
      compared with the BIA group. CONCLUSION: Our results suggest that brief
      interventions (PMI and BIA) that link alcohol consumption with trauma injury and
      consequences of drinking can be effective in reducing drinking and consequences
      related to drinking in a significant portion of at-risk nondependent drinkers.

PMID- 17495709
TI  - How dangerous is BASE jumping? An analysis of adverse events in 20,850 jumps from
      the Kjerag Massif, Norway.
AB  - BACKGROUND: Extreme sports, including BASE (building, antenna, span, earth)
      jumping, are rapidly increasing in popularity. Associated with risk for injuries
      and deaths, this activity may pose a burden on the emergency system. Hitherto, no
      reports exist on accidents and deaths associated with BASE jumping. METHODS: We
      reviewed records of 20,850 BASE jumps from 1995 to 2005 at the Kjerag massif in
      Norway. Frequency of deaths, accidents, and involvement of helicopter and
      climbers in rescue are analyzed. Fatalities were scored for injury severity
      scores (Abbreviated Injury Scale score, Injury Severity Score, New Injury
      Severity Score) on autopsy. RESULTS: During an 11-year period, a total of 20,850
      jumps (median, 1,959; range, 400-3,000) resulted in 9 fatal (0.04% of all jumps;
      1 in every 2,317 jumps) and 82 nonfatal accidents (0.4% of all jumps; 1 in every
      254 jumps). Accidents increased with the number of jumps (r=0.66; p=0.007), but
      fatalities did not increase, nor did activation of helicopter or climbers in
      rescue (p>0.05). Helicopter activation (in one-third of accidents) in rescue
      correlated with number of accidents (r=0.76, p=0.007), but not climbers.
      Postmortem examination (n=7) of fatalities revealed multiple, severe injuries
      (Abbreviated Injury Scale score>or=3) sustained in several body regions (median,
      Injury Severity Score 75; range, 23-75). Most nonfatal accidents were related to
      ankle sprains/fracture, minor head concussion, or a bruised knee. CONCLUSION:
      BASE jumping appears to hold a five- to eightfold increased risk of injury or
      death compared with that of skydiving. The number of accidents and helicopter
      activation increases with the annual number of jumps. Further analysis into the
      injury severity spectrum and associated hospital burden is required.

PMID- 17495710
TI  - The current injury situation of bicyclists--a medical and technical crash
      analysis.
AB  - BACKGROUND: The purpose of the study was to analyze the actual injury situation
      of bicyclists in Germany to create a basis for effective preventive measures.
      METHODS: Technical and medical data were prospectively collected shortly after
      the crash at the crash scenes. RESULTS: Included were 4,264 injured bicyclists
      from 1985 to 2003. Fifty-five percent of the bicyclists were male and 45% were
      women. The mean age of bicyclists was 52.0 years. The crashes took place in urban
      areas in 95.2% of the cases, and in rural areas in 4.8% of the cases. Collision
      opponents were cars in 65.8%, trucks in 7.2%, bicyclists in 7.4%, standing
      objects in 8.8%, multiple opponents or objects in 4.3%, and others in 6.5%. The
      mean collision speed was 21.3 km/h. The helmet use rate was 1.7%. Fifty-five
      percent of bicyclists used bicycle traffic lanes before the crash. The mean
      Maximum Abbreviated Injury Scale/Injury Severity Score (ISS) was 1.45 of 3.9. The
      incidence of multiple injuries (ISS>16)/death was 2.0%/1.5%. The ISS/Maximum
      Abbreviated Injury Scale score was higher in bicyclists without a helmet than in
      bicyclists with a helmet, and in bicyclists who had not used bicycle traffic
      lanes than in bicyclists who had used bicycle traffic lanes (t test, p<0.05).
      CONCLUSION: In bicyclists, head and extremities are at high risk for injuries.
      The helmet use rate is unsatisfactorily low. Remarkably, two-thirds of the head
      injuries could have been prevented by helmets. More consequent helmet use and an
      extension of bicycle traffic lanes for a better separation of bicyclists and
      motorized vehicles would be simple but very effective preventive measures.

PMID- 17495711
TI  - Experience with railroad injuries at a major urban trauma center serving the
      United States-Mexico border.
AB  - BACKGROUND: In the United States (US), railroads are commonly used to transport
      humans and commerce, especially along the US-Mexico border. Some people will use
      freight trains to travel within the US. Some of these people will suffer a train
      related injury with extensive soft tissue and bone trauma. There is little
      information about the demographics, injuries, or outcomes of these patients, and
      the financial expense of providing care for these individuals. We attempt to
      provide insight into some of these issues. METHODS: We performed a retrospective
      chart review of patients from the University of Texas Health Science Center at
      San Antonio from January 1996 to September 2003. Various demographic, total
      hospital costs, operative procedures, and outcomes were examined. RESULTS: Men
      were well represented (61 of 67 patients), and the overall mean age was 28.8
      years. Hispanics (58 of 67 patients) were the main ethnic group and 61% were
      undocumented aliens (41 of 67 patients). Bony and soft tissue injuries were
      common, necessitating an amputation in 38 patients. The mean operative procedures
      per patient were 2.97. Follow-up was poor. Total hospital cost for all the
      patients was $2,468,004.47 with a mean of $36,835.89 ($1,305.00-$331, 452.74) per
      patient. CONCLUSION: Victims of train-related injuries were predominantly young
      and male. Many patients required an amputation. Multistaged and complex
      reconstructive procedures may not be realistic in a group of patients in whom
      follow-up is poor.

PMID- 17495712
TI  - Assessing behind armor blunt trauma in accordance with the National Institute of
      Justice Standard for Personal Body Armor Protection using finite element
      modeling.
AB  - BACKGROUND: To assess the possibility of injury as a result of behind armor blunt
      trauma (BABT), a study was undertaken to determine the conditions necessary to
      produce the 44-mm clay deformation as set forth in the National Institute of
      Justice (NIJ) Standard 0101.04. These energy levels were then applied to a three
      dimensional Human Torso Finite Element Model (HTFEM) with soft armor vest. An
      examination will be made of tissue stresses to determine the effects of the
      increased kinetic energy levels on the probability of injury. METHODS: A clay
      finite element model (CFEM) was created with a material model that required
      nonlinear properties for clay. To determine these properties empirically, the
      results from the CFEM were matched with experimental drop tests. A soft armor
      vest was modeled over the clay to create a vest over clay block finite element
      model (VCFEM) and empirical methods were again used to obtain material properties
      for the vest from experimental ballistic testing. Once the properties for the
      vest and clay had been obtained, the kinetic energy required to produce a 44-mm
      deformation in the VCFEM was determined through ballistic testing. The resulting
      kinetic energy was then used in the HTFEM to evaluate the probability of BABT.
      RESULTS: The VCFEM, with determined clay and vest material properties, was
      exercised with the equivalent of a 9-mm (8-gm) projectile at various impact
      velocities. The 44-mm clay deformation was produced with a velocity of 785 m/s.
      This impact condition (9-mm projectile at 785 m/s) was used in ballistic
      exercises of the HTFEM, which was modeled with high-strain rate human tissue
      properties for the organs. The impact zones were over the sternum anterior to T6
      and over the liver. The principal stresses in both soft and hard tissue at both
      locations exceeded the tissue tensile strength. CONCLUSIONS: This study indicates
      that although NIJ standard 0101.04 may be a good guide to soft armor failure, it
      may not be as good a guide in BABT, especially at large projectile kinetic
      energies. Further studies, both numerical and experimental, are needed to assist
      in predicting injury using the NIJ standard.

PMID- 17495713
TI  - Repeated thoracic discharges from a stun device.
AB  - BACKGROUND: Little objective laboratory data are available describing the
      physiologic effects of stun guns or electromuscular incapacitation (EMI) devices,
      but increasing morbidity and even deaths are associated with their use. We
      hypothesized that exposure to EMI discharges in a model animal system would
      induce clinically significant acidosis and cardiac arrhythmia. METHODS: Ten
      Yucatan mini-pigs, six experimental and four sham controls, were anesthetized
      with ketamine, xylazine, and glycopyrrolate. Experimental pigs were exposed to
      two 40-second discharges from an EMI device over the left thorax.
      Electrocardiograms, troponin I, blood gases, and lactate levels were obtained pre
      exposure, at 5, 15, 30, 60 minutes, and at 24, 48, and 72 hours postdischarge.
      RESULTS: No acute or delayed cardiac arrhythmias were seen. Heart rate was not
      affected significantly (p>0.05). A subclinical increase in troponin I was seen at
      24 hours postdischarge (0.040+/-0.030 ng/mL, p>0.05). Central venous blood pH
      (7.432+/-0.014) and pCO2 (36.1+/-0.9 mm Hg) were not changed significantly
      (p>0.05) during the 60-minute postdischarge period. A moderate significant
      increase in lactate occurred in the 5-minute postdischarge group (4.9+/-0.3
      mmol/L, p=0.0179). All blood chemistry and vital signs were normal at 24, 48, and
      72 hours postdischarge. CONCLUSIONS: Although significant changes in some
      parameters were seen, these changes were small and of little clinical
      significance. Lengthy EMI exposures did not cause extreme acidosis or cardiac
      arrhythmias. These findings may differ from those seen with other EMI devices
      because of the unique MK63 waveform characteristics or to specific
      characteristics of the model systems.

PMID- 17495714
TI  - The utility of serial computed tomography imaging of blunt splenic injury: still
      worth a second look?
AB  - BACKGROUND: Serial computed tomography (CT) imaging of blunt splenic injury (BSI)
      can identify the latent formation of splenic artery pseudoaneurysms (PSAs),
      contributing to improved success in splenic salvage. The practice of serial CT
      imaging, however, has not been embraced. The purpose of this study was to
      reevaluate the clinical practice of serial CT imaging within the context of an
      institutional protocol for the nonoperative management (NOM) of BSI. METHOD:
      Consecutive patients with BSI selected for NOM were identified from our trauma
      registry. Patients were managed according to protocol, whereby hemodynamically
      stable patients with PSA on initial or follow-up CT imaging were referred for
      angiography. Follow-up CT was performed 24 to 48 hours after the initial CT. Data
      were abstracted from hospital, clinic, and radiology records, and included age,
      Injury Severity Score, splenic injury grade (SIG), and CT findings. The incidence
      and timing of PSA identification with respect to subsequent management and
      outcome were reviewed. RESULTS: Of 426 BSI admissions during a 2.5-year period,
      341 (80%) were selected for NOM. Mean follow-up was 39 days, with 76% followed
      for >or=7 days. Serial CT imaging resulted in the angiographic detection of 14
      (4%) early PSAs and 11 (3%) latent PSAs. PSAs were associated with increasing SIG
      (p<0.001); however, 24% of PSAs were observed in SIG 1 and 2. Embolization was
      successful in 13 of 14 (93%) patients with early PSAs and 10 of 11 (91%) with
      latent PSAs. The splenic salvage rate for all patients selected for NOM during
      the study period was 329 of 341 (97%). CONCLUSIONS: Adherence to a NOM protocol
      guided by serial CT imaging has resulted in one of the highest splenic salvage
      rates reported to date. Identification and embolization of latent PSA likely
      contributes to NOM success, given the unfavorable natural history of these
      lesions. Although PSA formation is correlated with increasing SIG, PSAs are not
      exclusive to higher-grade injury, warranting serial CT surveillance regardless of
      SIG.

PMID- 17495715
TI  - Significance of contrast extravasation in patients with pelvic fracture.
AB  - BACKGROUND: Contained contrast extravasation (CE) in solid organ injury is not
      well correlated with the need for operative intervention, but the significance of
      CE in patients with pelvic fracture is unknown. METHODS: The trauma registry at a
      Level I trauma center was queried for all patients with pelvic fracture from
      January 1, 1998 to May 31, 2005. All computed tomography (CT) scans used helical
      technology. Demographic and injury information were abstracted from the trauma
      registry and medical record. CT and angiography reports of all patients were
      reviewed. Angiograms and abdominal and pelvic CT studies (AP-CT) of patients with
      CE were then reviewed by a radiologist. RESULTS: A total of 604 patients with a
      pelvic fracture and an AP-CT were identified. Of these, 42 patients had a pelvic
      CE on CT study. Patients with CE had a higher Injury Severity Score (24.5 vs.
      18.3, p<0.001) and higher mortality (24 vs. 6%, p<0.001). Twenty-five patients
      with CE underwent angiography, with CE confirmed in 19 patients and embolization
      performed in 17. Six patients without CE underwent angiography. CE was confirmed
      in two patients and both were embolized. A significantly higher number of
      patients undergoing angiography required ongoing transfusion. CONCLUSIONS: CE is
      a marker of severe injury but does not mandate angiography. Associated injuries
      are common and other sources of blood loss must be excluded. CE is not reliable
      enough to exclude significant vascular injury, as the therapeutic embolization
      rate for CE-negative patients undergoing angiography is 33%.

PMID- 17495716
TI  - Changes in thoracolumbar computed tomography and radiography utilization among
      trauma patients after deployment of multidetector computed tomography in the
      emergency department.
AB  - BACKGROUND: Diagnostic-quality thoracolumbar spine (TLS) images, generated from
      routine thoracoabdominal multidetector computed tomography (MDCT) data, have been
      demonstrated superior to conventional radiography (CR) for TLS injury. We
      evaluated thoracoabdominal computed tomography (CT) and TLS utilization among
      trauma patients after deployment of MDCT. We hypothesized that reformatted MDCT
      images replaced CR for evaluation of TLS trauma among patients undergoing chest
      or abdominal CT, and that utilization of thoracoabdominal CT and TLS screening in
      trauma increased postMDCT. METHODS: We reviewed all TLS imaging for trauma
      patients undergoing chest or abdominal CT for 18 months pre- and postMDCT. We
      compared the relative use of CR and CT in TLS imaging, and the volume of TLS
      screening, and chest and abdominal CT across the study period. We also reviewed
      TLS CR in patients not undergoing chest or abdominal CT. RESULTS: After MDCT
      deployment, CT replaced CR for TLS imaging among those undergoing chest or
      abdominal CT for trauma. Utilization of chest and abdominal CT and TLS screening
      significantly increased, despite unchanged volume and severity of trauma patients
      during the study period. There was a corresponding decrease in patients evaluated
      with thoracic spine CR alone CONCLUSIONS: Reformatted TLS images using
      thoracoabdominal CT data have replaced CR in our evaluation of TLS trauma.
      However, reasons for increased utilization remain unclear. Further studies are
      needed to determine whether clinical yield and cost-effectiveness warrant these
      changes in utilization.

PMID- 17495717
TI  - Nonunion after functional brace treatment of diaphyseal humerus fractures.
AB  - OBJECTIVE: To assess which fractures of the humeral diaphysis are prone to
      nonunion after functional bracing by analyzing patients that present for
      treatment of nonunion after brace treatment. METHODS: Thirty-two patients treated
      operatively for a nonunion of the diaphyseal humerus after functional brace
      treatment were analyzed with respect to the location and the pattern of the
      original fracture. There were 21 women and 11 men with an average age of 53 years
      (range 23-84 years). RESULTS: The fracture involved the proximal third of the
      diaphysis in 17 patients, the middle third in 14 patients, and the distal third
      in 1 patient. The pattern of the fracture was oblique or spiral in 27 patients
      with a butterfly fragment in 11 of those patients. Only four patients had a
      transverse fracture. Operative fixation ultimately achieved union in all 32
      patients, but a second procedure was necessary for loosening of fixation or
      persistent nonunion in 3 older-aged patients. The functional results were good or
      excellent in all 32 patients. CONCLUSIONS: Compared with the epidemiology of
      acute diaphyseal humerus fractures, nonunions after functional bracing are more
      likely to follow spiral/oblique fractures that involve the mid- or proximal-third
      of the diaphysis. Operative treatment can gain union and improve arm function.

PMID- 17495718
TI  - The value of conservative treatment in ruptures of the anterior cruciate ligament
      (ACL).
AB  - BACKGROUND: Thirty-eight of the 73 consecutive acute ruptures of the anterior
      cruciate ligament (ACL) proven by a magnetic resonance imaging scan (MRI) in
      skeletally mature patients (16-55 years old) were classified as suitable for
      primarily conservative treatment. Patient selection was performed using a
      preoperative screening protocol based on the structural damage, clinical
      symptoms, compliance, sportive activity, and the consent of a well-informed
      patient. METHODS: In 12 of the 38 treated patients, the conservative protocol
      showed a good to very good outcome, 2 patients had persistent giving-way and were
      considering ACL reconstruction, 14 patients had a secondary ACL reconstruction in
      our clinic (average 5.3 months after injury), 9 patients were operated on in
      other hospitals (average 13.3 months after injury), and 1 patient was lost to
      follow-up. RESULTS: All patients with successful conservative treatment were able
      to perform low-risk pivoting sports and two patients are practicing high-risk
      pivoting sports. The average International Knee Documentation Committee (IKDC)
      score was 92.5 (82.8-98.9); the subjective overall knee function was 93% (60% to
      100%). Of the 12 patients with good and very good results, 6 continued playing
      the same sports at an unreduced intensity, 4 patients reduced their activities
      slightly, and 1 patient played more sports than before. CONCLUSIONS: Although the
      authors performed a preoperative screening to select patients suitable for
      conservative treatment, almost two-thirds of the primarily conservatively treated
      ACL ruptures needed an operative reconstruction in the long term. In one-third of
      the patients, conservative treatment led to a good or very good result. At the
      endpoint of the study only 12 (16%) of a total of 73 patients with acute injuries
      of the ACL had successful conservative treatment. Therefore, patients must be
      comprehensively instructed about the treatment program and the chances of success
      of conservative ACL treatment.

PMID- 17495719
TI  - Orthopedic trauma from recreational all-terrain vehicle use in central Kentucky:
      a 6-year review.
AB  - BACKGROUND: All-terrain vehicle (ATV) crashes and injuries have become an
      increasing concern for the medical community. After the expiration of federal
      guidelines in 1998, the United States Consumer Product Safety Commission has
      tracked an increasing incidence of usage and injury. This retrospective review of
      data from a Level I trauma center presents ATV crash-related injury prevalence,
      type, and location sustained in central Kentucky and compares the data with
      previous reports. METHODS: Patient demographics, helmet and alcohol use,
      insurance type, injury type and location, Injury Severity Score (ISS), Glasgow
      Coma Scale (GCS) score, Functional Independence Measure (FIM), duration of
      hospital stay, days in an intensive care unit (ICU), internal disposition, and
      discharge destination were analyzed among individuals who had sustained ATV crash
      related injuries between January 1998 and December 2003. RESULTS: Patients were
      primarily male (85.4%), white (98%), resided in a rural county (85.1%), and
      relied on commercial insurance (36.2%) or self-pay (31.4%) for medical expenses.
      Alcohol use before injury was documented for 25% and 85.5% were not wearing a
      helmet. Rollover was the primary ATV crash mechanism (63.3%) and 52.1% of
      patients lost consciousness. Of 707 total injuries, 319 (45.1%) were fractures or
      dislocations with the spine (26%), ribs (24.1%), clavicle (6%), radius-ulna
      (5.3%), and tibia-fibula (4.7%) being the most common locations. Admitted
      patients were hospitalized for 8.1+/-12.7 days (range=0-127 days), 42% were
      transferred to the standard care ward, 28.2% spent 8.4+/-7.7 days (range=1-34
      days) in the ICU, and 18.6% were taken directly to the operating room. At
      discharge 78.2% of patients went home, 12.8% were transferred to a rehabilitation
      facility, 4.8% died, and 3.2% were transferred to another hospital. Patients who
      never lost consciousness or who were discharged to home had lower ISSs and
      greater composite and component GCS and FIM scores. CONCLUSION: Almost half of
      all patients sustained one fracture or joint dislocation with the spine being the
      most prevalent location. Injury severity, the low number referred to
      rehabilitation facilities, and predominantly rural residence locations suggests
      that many may not be accessing needed healthcare services. Prospective
      longitudinal outcome studies are needed to assess patient functional
      independence, quality of life, and health care system effectiveness.

PMID- 17495720
TI  - Multiple subfailures characterize blunt aortic injury.
AB  - BACKGROUND: Blunt aortic injuries result from rapid deceleration of the thorax as
      may occur during automotive impacts and falls from extreme heights. Pathological
      findings can range from failure of specific vessel layers to immediate vessel
      wall rupture. The purpose of this investigation was to determine the sequence of
      local structural events that may lead to aortic wall disruption. METHODS:
      Fourteen porcine aorta specimens were opened to expose the intima and
      longitudinally distracted until rupture. Longitudinal mechanics were quantified
      and subfailures were identified. Histology was used to examine internal layer
      subfailure. RESULTS: Videography demonstrated that subfailures propagated into
      complete vessel wall rupture. Subfailures occurred before complete vessel rupture
      in 93% of specimens. Intimal and medial subfailures were present at 74% of the
      stress and 82% of the strain to rupture. Multiple subfailures were evident in 79%
      of specimens. CONCLUSION: Present results supported the clinical theory that
      nonimmediate death as a result of blunt aortic injury is commonly caused by
      propagation of lesser lesions, initiating on the intimal layer, into complete
      vessel rupture including the adventitial layer. This finding, along with
      histologic evidence of subfailure pathological findings, confirms the presence of
      an acute window during which recognition and initiation of permissive hypotension
      may be lifesaving.

PMID- 17495721
TI  - Intrapleural thrombolysis for the management of undrained traumatic hemothorax: a
      prospective observational study.
AB  - BACKGROUND: Tube thoracostomy is usually sufficient treatment for traumatic
      hemothorax. Occasionally, significant residual collections remain undrained. Open
      thoracotomy and video-assisted thoracoscopic surgery (VATS) have been used to
      manage undrained traumatic hemothoraces (UTHs). Both techniques are invasive and
      harbor risks. More recently, intrapleural administration of thrombolytic agents
      (streptokinase and urokinase) has been reported as an effective nonoperative
      treatment of residual collections caused by a variety of diseases. The role of
      intrapleural thrombolysis (IT) for the treatment of an UTH is inadequately
      explored. METHODS: Patients with an UTH, defined as more than 300 mL of
      intrathoracic blood estimated by computed tomographic scan on the third day after
      chest tube insertion, were followed prospectively for 16 months. IT was
      instituted according to a standardized protocol using streptokinase or urokinase.
      IT effectiveness, defined by the incidence of successful resolution of the UTH,
      and IT safety, defined by the incidence of uncomplicated therapy, was calculated.
      RESULTS: Of 203 patients with a traumatic hemothorax, managed by tube
      thoracostomy, 25 (12.3%) developed an UTH. Successful resolution of the UTH was
      achieved in 23 (92%) patients within 3.4+/-1.4 days. No bleeding or other
      significant complications related to IT were recorded. CONCLUSIONS: IT should be
      the initial treatment of choice for the management of an UTH.

PMID- 17495722
TI  - Cost-utility analysis of emergency department thoracotomy for trauma victims.
AB  - BACKGROUND: Our objective was to assess the cost-effectiveness of emergency
      department thoracotomy (EDT) performed on both penetrating and blunt trauma
      victims, using both published survival and outcome data and previously
      unaccounted for data on the cost of occupational exposure. METHODS: Cost-utility
      analysis was performed using decision-analytic models constructed for both
      penetrating and blunt trauma scenarios. Survival and impairment data, the rates
      and costs of occupational exposure, and the utilities of neurologic impairment
      and provider seroconversion were all based on published literature. Costs of EDT
      were estimated using the National Inpatient Sample (NIS) from the Health Care
      Utilization Project database. One-way sensitivity analyses on input parameters
      and probabilistic sensitivity analyses using Monte Carlo simulations were
      performed. RESULTS: The incremental cost-effectiveness ratio of EDT for
      penetrating trauma was $16,125 per quality-adjusted life year (QALY), and less
      than $50,000 per QALY with a 93.4% probability. The incremental cost
      effectiveness ratio for blunt trauma was $163,136 per QALY, and less than $50,000
      per QALY with a 37% probability. Neither model was sensitive to provider
      exposure. The penetrating model was insensitive to the probability of
      neurologically intact survival, the utility adjustment, procedure costs, and long
      term care. The blunt model was sensitive to the probabilities of survival and of
      neurologic impairment. CONCLUSIONS: EDT is cost-effective for penetrating trauma,
      and not cost-effective for blunt trauma given current rates of survival and
      impairment. Occupational exposure does not significantly impact the cost
      effectiveness of the procedure.

PMID- 17495723
TI  - Trauma associated with cardiac dysrhythmias: results from a large matched case
      control study.
AB  - BACKGROUND: Various cardiac dysrhythmias such as supraventricular and ventricular
      premature beats, supraventricular and ventricular paroxysmal tachycardia, atrial
      and ventricular fibrillation and atrial flutter have been reported in case
      series, as complications of blunt cardiac and thoracic trauma. The objective of
      this research was to determine whether thoracic or blunt cardiac injury is
      associated with cardiac dysrhythmia in a large multistate hospitalized
      population. METHODS: Cases and matched (by age) controls were identified based on
      hospital discharge information that was collected from 986 acute general
      hospitals across 33 states in 2001. Both the exposure (thoracic trauma and blunt
      cardiac injury) and the outcome (cardiac dysrhythmias) were identified based on
      ICD-9-CM discharge diagnoses. Unadjusted and conditional adjusted (for gender,
      race, length of stay, and primary source of payment) multivariate logistic
      regression analyses were performed. RESULTS: After adjusting for potential
      confounders, patients 50 years and younger diagnosed with blunt cardiac injury
      had a fourfold (95% confidence interval, 1.40-11.60) increase in the risk of
      cardiac dysrhythmia. Independent of potential confounding factors, discharge for
      blunt cardiac injury among patients 51 to 70 years old was associated with a
      twofold (95% confidence interval, 1.36-3.82) increased risk for cardiac
      dysrhythmia. CONCLUSION: Blunt cardiac injury was found to be a significant risk
      factor for cardiac dysrhythmia. Longitudinal studies are needed to better
      establish the association between trauma and cardiac dysrhythmias.

PMID- 17495724
TI  - Effects of age and obesity on hemodynamics, tissue oxygenation, and outcome after
      trauma.
AB  - OBJECTIVE: The aims of this study are (1) to describe the early time course of
      hemodynamic and tissue perfusion/oxygenation patterns in the elderly and in obese
      patients who survive and those who die after trauma; and (2) to evaluate
      postinjury hemodynamic patterns for use as guides for resuscitation and
      subsequent treatment. METHODS: We noninvasively monitored 625 trauma patients
      upon arrival in the emergency department to assess the temporal hemodynamic
      patterns associated with age and obesity. Cardiac index (CI), mean arterial
      pressure, and heart rate were monitored to assess cardiac function, pulse
      oximetry (Sapo2) to reflect changes in pulmonary function and transcutaneous
      oxygen (PtcO2), carbon dioxide (PtcCO2), and oxygen delivery (DO2) to reflect
      tissue perfusion. We evaluated these hemodynamic data after they were stratified
      by the patient age and body mass index. RESULTS: When all trauma patients were
      considered together, the predominant findings were high CI, transient
      hypotension, tachycardia, normal pulmonary function, and reduced tissue
      oxygenation. The elderly and, to a lesser extent the obese, had lower flow and
      tissue perfusion. The survivors had higher CI and better tissue oxygenation than
      did the nonsurvivors of each category. CONCLUSIONS: Elderly and obese
      nonsurvivors of severe injury had low CI with reduced tissue oxygenation
      associated with organ failures and death. The study suggests that survivors' CIs
      and tissue oxygenation may be used as markers of circulatory deterioration and
      shock as well as resuscitation.

PMID- 17495725
TI  - Prone ventilation in trauma or surgical patients with acute lung injury and adult
      respiratory distress syndrome: is it beneficial?
AB  - BACKGROUND: To compare the effectiveness of supine versus prone kinetic therapy
      in mechanically ventilated trauma and surgical patients with acute lung injury
      (ALI) and adult respiratory distress syndrome (ARDS). METHODS: A retrospective
      review of all patients with ALI/ARDS who were placed on either a supine (roto
      rest) or prone (roto-prone) oscillating bed was performed. Data obtained included
      age, revised trauma score (RTS), base deficit, Injury Severity Score (ISS), head
      Abbreviated Injury Scale score (AIS), chest (AIS), PaO2/FiO2 ratio, FiO2
      requirement, central venous pressure (CVP), days on the bed, ventilator days, use
      of pressors, complications, mortality, and pulmonary-associated mortality. Data
      are expressed as mean+/-SE with significance attributed to p<0.05. RESULTS: From
      March 1, 2004 through May 31, 2006, 4,507 trauma patients were admitted and 221
      were identified in the trauma registry as having ALI or ARDS. Of these, 53 met
      inclusion criteria. Additionally, 8 general surgery patients met inclusion
      criteria. Of these 61 patients, 44 patients were positioned supine, 13 were
      placed prone, and 4 patients that were initially placed supine were changed to
      prone positioning. There was no difference between the groups in age, CVP, ISS,
      RTS, base deficit, head AIS score, chest AIS score, abdominal AIS score, or
      probability of survival. The PaO2/FiO2 ratios were not different at study entry
      (149 vs. 153, p=NS), and both groups showed improvement in PaO2/FiO2 ratios.
      However, the prone group had better PaO2/FiO2 ratios than the supine group by day
      5 (243 vs. 200, p=0.066). The prone group had fewer days on the ventilator (13.6
      vs. 24.2, p=0.12), and shorter hospital lengths of stay (22 days vs. 40 days,
      p=0.08). There were four patients who failed to improve with supine kinetic
      therapy that were changed to prone kinetic therapy. These patients had
      significant improvements in PaO2/FiO2 ratio, and significantly lower FiO2
      requirements. There were 18 deaths (7 pulmonary related) in the supine group and
      1 death in the prone group (p < 0.01 by chi test). CONCLUSIONS: ALI/ARDS patients
      who received prone kinetic therapy had greater improvement in PaO2/FiO2 ratio,
      lower mortality, and less pulmonary-related mortality than did supine positioned
      patients. The use of a prone-oscillating bed appears advantageous for trauma and
      surgical patients with ALI/ARDS and a prospective, randomized trial is warranted.

PMID- 17495726
TI  - Agreement between emergency room and discharge diagnoses in a population of
      injured inpatients: determinants and mortality.
AB  - BACKGROUND: Various factors contribute to the quality of care of an injured
      patient at the emergency room (ER), and a correct diagnosis can improve and
      accelerate care. The aim of this study was to evaluate the agreement between
      diagnoses assigned in the ER and those assigned after hospital admission to
      patients with unintentional injuries. We also tried to determine the factors that
      influenced the disagreement, and to evaluate if discordant diagnoses were
      associated with higher mortality risk. METHODS: All ER visits for unintentional
      injuries that were followed by hospital admission at the 60 emergency departments
      in the Lazio Region in 2000. Concordant diagnoses (ER/discharge) were established
      based on the Barell matrix cells. Logistic regression was used to assess the role
      of individual and ER care factors on the probability of concordance. A logistic
      regression was performed, where death within 30 days was the outcome and
      concordance was the determinant. RESULTS: We considered 22,892 ER visits for
      injury that were followed by hospital admission. In 62.2% of cases, the ER and
      discharge diagnoses were concordant. Higher concordance was found for older
      patients and less urgent cases. Factors influencing concordance were the hour of
      the visit, ER specialization degree, initial outcome, and length of hospital
      stay. Patients who had disconcordant diagnoses had a 30% higher probability of
      death. CONCLUSIONS: A correct diagnosis (i.e. confirmed at hospital discharge) at
      first contact with the emergency room is associated with lower mortality.
      Comparing administrative ER and hospital discharge data can be useful in
      emergency department management studies.

PMID- 17495727
TI  - An analysis of hospital trauma care performance evaluation.
AB  - OBJECTIVE: The purpose of this article was to report on a study on the hospital
      trauma care performance evaluation based on a database of trauma events of
      participating UK and European hospitals. METHODS: Performance evaluation has
      become increasingly important in the quality assessment of health care in general
      and trauma care in particular. For many years, attempts to quantifying the
      performance of trauma care systems on a numerical scale have been developed and
      applied, including the use of Ws statistic. The Trauma Audit and Research Network
      collected and managed the data. We first investigated the currently used
      approaches in the evaluation of trauma care systems, and then proposed an
      alternative using a statistical control based approach for the comparison of
      different hospitals at one time. Different control charts and types of
      calculations were also proposed for the chronologic outcome chart, which plots
      the variation of trauma care within one hospital over time. RESULTS: New
      graphical methods for hospital trauma care performance evaluation based on
      statistical process plots were developed and tested on the project database.
      CONCLUSION: A control chart approach to the presentation of the outcome charts
      for hospital trauma care performance evaluation is presented in this article. The
      charts are more meaningful than the "caterpillar" plot traditionally used, and
      avoid the ranking of institutions into "league tables".

PMID- 17495728
TI  - Implementation of a rapid response team decreases cardiac arrest outside of the
      intensive care unit.
AB  - BACKGROUND: Patient safety and preventable inhospital mortality remain crucial
      aspects of optimum medical care and continue to receive public scrutiny. Signs of
      physiologic instability often precede overt clinical deterioration in many
      patients. The purpose of this study was to evaluate our early experience with
      implementation of a rapid response team (RRT) which would evaluate and treat
      nonintensive care unit (nonICU) patients with early signs of physiologic
      instability. We hypothesized that early evaluation and intervention before
      deterioration would avoid progression to cardiac arrest in patients. METHODS: In
      March 2005, our urban Level I trauma center implemented an RRT to react to
      patient clinical deterioration; in effect, bringing critical care to the bedside.
      This team is available 24 hours/day, 7 seven days/week and consists of an
      intensivist, an ICU nurse, and a respiratory therapist. Activation criteria
      include pulse<40 or>130 beats per minute, systolic blood pressure<90 mm Hg,
      respiratory rate<8 or>24 breaths per minute, seizure, an acute change in mental
      status, or nursing staff concern for any other reason. Data were prospectively
      collected, including the number of RRT activations and the occurrence of
      inhospital cardiac arrest. RESULTS: Between March and December 2005, the RRT was
      activated 76 times. All RRT activations were reviewed and thought to be
      appropriate. During the same time period the year before initiation of the RRT,
      there were 27 nonICU cardiac arrests. After RRT implementation, there were 13
      cardiac arrests that occurred on the floor, representing just over a 50%
      reduction in cardiac arrest. Medical staff feedback regarding the RRT was
      uniformly positive. CONCLUSIONS: Implementation of the RRT was well received by
      the hospital staff. Despite initial concerns to the contrary, the RRT was not
      over utilized. RRT activation resulted in early patient transfer to a higher
      level of care and avoided progression to cardiac arrest.

PMID- 17495729
TI  - Transfer of pediatric trauma patients to a tertiary pediatric trauma centre:
      appropriateness and timeliness.
AB  - OBJECTIVE: To study the appropriateness of, and time taken, to transfer pediatric
      trauma patients in New South Wales to The Children's Hospital at Westmead (CHW),
      a pediatric trauma center. METHODS: All trauma patients transferred to CHW from
      June 2003 to July 2004 were included in the study. Indications and time periods
      relevant to the transfer of the patient from the referring institute were
      retrieved and analyzed. Pediatric and adult retrieval services were compared.
      RESULTS: Three hundred ninety-eight patients were transferred to CHW, of whom 332
      were from the metropolitan region. Falls and burns were the commonest mechanism
      of injury. Burn was the commonest indication for transfer (107 of 398). Mean
      Injury Severity Score was eight. Nearly half the patients had minor injuries
      (Injury Severity Score<9). Patients spent an average of 5 hours at the referring
      hospital. Pediatric retrieval ambulances had significantly longer mean transfer
      times than did nonpediatric ambulance services with a total time spent of about
      2.64 hours versus 1.30 hours, respectively. For aeromedical transfers, on the
      other hand, the difference between pediatric retrieval services and nonpediatric
      air ambulances was not significant. CONCLUSIONS: The majority of the patients
      transferred had minor injuries. Pediatric trauma patients spend considerable time
      in their referring hospitals. Pediatric retrieval services appear to take
      significantly longer to transfer patients than nonpediatric ambulance transfers
      even after allowing for patient age and injury severity. Although this did not
      result in mortality or morbidity, there appears to be considerable scope for a
      reduction in transfer times through better coordination of these services.

PMID- 17495730
TI  - Civilian hospital response to a mass casualty event: the role of the intensive
      care unit.
AB  - BACKGROUND: We studied the response of the Shaare Zedek Medical Center (SZMC) in
      Jerusalem, Israel, to terrorist multiple- or mass-casualty events (TMCEs) that
      occurred between 1983 and 2004, to document the role of the intensive care unit
      (ICU) in this response. METHODS: The SZMC Disaster Plan was reviewed in detail.
      Hospital and ICU records were retrospectively reviewed for all patients
      presenting to SZMC between 1983 and 2004 after a TMCE. Data were coded for age,
      sex, injuries, length of stay, and mortality. RESULTS: Eight hundred seventy-five
      patients presented to SZMC after 31 TMCEs. The number of patients presenting
      ranged from 1 to 84 with an average of 28 patients per TMCE. Forty-one (4.7%) of
      the patients were admitted to the ICU. The age of the ICU patients ranged from 4
      to 80 with an average of 30.9 years. Twenty-nine (70%) of the patients had blast
      lung injury, 3 (7%) had intestinal blast injury, and 30 (73%) had ruptured
      tympanic membranes. Forty-two surgical procedures were performed in 23 patients.
      Thirty (73%) patients required mechanical ventilation. One patient (2.4%) died of
      multiple organ failure caused by a delay in diagnosis of intestinal blast injury.
      CONCLUSION: Of the patients presenting to SZMC after TMCE, 4.7% required ICU
      care. Seventy-three percent of the ICU patients required mechanical ventilation.
      The ICU plays a critical role in the SZMC response to TMCEs.

PMID- 17495731
TI  - A comprehensive renal injury concept based on a validated finite element model of
      the human abdomen.
AB  - BACKGROUND: The identification of abdominal injury mechanisms, development of
      effective countermeasures, and refinement of clinical approach to injury
      treatment are greatly facilitated by the employment of numerical models that can
      predict injuries resulting from complicated soft tissue interactions during blunt
      abdominal impact. METHODS: The present study introduces a detailed three
      dimensional finite element model of the human abdomen that was developed
      specifically for the investigation of renal trauma. The model geometry and
      materials reflect the complex mechanical environment of the abdomen, and is
      validated against both published and novel experiments. RESULTS: It is shown that
      use of the proposed model, in combination with appropriate mechanical organ
      injury criteria, provides a significant step toward a comprehensive renal injury
      concept. Specifically, the abdominal model offers the possibility to investigate
      injury likelihood and identify injury mechanisms over a broad range of impact
      loading scenarios. CONCLUSIONS: A sophisticated numerical model of renal trauma
      has been developed that can be used to effectively predict renal injury outcome
      for lateral impact.

PMID- 17495732
TI  - Timing of surgery after multisystem injury with traumatic brain injury: effect on
      neuropsychological and functional outcome.
AB  - OBJECTIVE: The optimal timing for noncranial surgery after multisystem injury is
      not known. Early surgery may lead to decreased pulmonary complications and length
      of stay, but also predispose to secondary brain injury if decreased cerebral
      perfusion occurs intraoperatively. Previous work has not consistently evaluated
      neuropsychological or functional outcome. We sought to determine whether 6-month
      neuropsychological and functional outcome was associated with timing of
      noncranial surgery after traumatic brain injury. MATERIALS: We performed a cohort
      study to evaluate the effect of timing of non-neurosurgical operative
      interventions on neuropsychological and functional outcome, morbidity, and
      mortality. Early surgery was defined as <or=24 hours after injury, and late
      surgery, >24 hours after injury but during the same admission. Patients with a
      nonoperative brain injury and an operative facial or orthopedic fracture were
      selected from two randomized trials previously performed at our Level I trauma
      center. Data were abstracted from medical records and outcome had been
      prospectively gathered as part of the two clinical trials. RESULTS: Patients
      undergoing early or late surgery had similar demographics, overall injury
      severity, traumatic brain injury severity, and admission characteristics. The
      early group had more open orthopedic fractures, but also underwent multiple
      operations more often than did the late group. At 6 months postinjury, patients
      in the early group had a better composite neuropsychological score than did those
      in the late group on unadjusted analysis and after including a propensity score.
      After adjusting for potential confounders, this difference was significant. No
      significant differences in return to work or Glasgow Outcome Score were noted.
      The late group had a higher incidence of pneumonia and a longer hospital stay
      (p<0.10). CONCLUSIONS: In traumatic brain injury patients with multisystem
      trauma, early timing of orthopedic and facial fracture fixation under general
      anesthesia was not associated with worse neuropsychological or functional outcome
      when compared with the outcomes associated with late surgery. Clinical
      conclusions may be limited by inherent selection bias and unmeasured confounding.
      However, these results contribute to equipoise regarding timing of surgery after
      multiple injuries, and emphasize the need for a randomized trial.

PMID- 17495733
TI  - Black children experience worse clinical and functional outcomes after traumatic
      brain injury: an analysis of the National Pediatric Trauma Registry.
AB  - BACKGROUND: Recent studies suggest racial disparities in the treatment and
      outcomes of children with traumatic brain injury (TBI). This study aims to
      identify race-based clinical and functional outcome differences among pediatric
      TBI patients in a national database. METHODS: A total of 41,122 patients (ages 2
      16 years) who were included in the National Pediatric Trauma Registry (from 1996
      2001) were studied. TBI was categorized by Relative Head Injury Severity Score
      (RHISS) and patients with moderate to severe TBI were included. Individual race
      groups were compared with white as the majority group. Differences between races
      in functional outcomes at discharge in three domains-speech, locomotion, and
      feeding-were determined using multiple logistic regression. Cases were adjusted
      for age, sex, severity of head injury (using RHISS), severity of injury (using
      New Injury Severity Score and Pediatric Trauma Score), premorbidities, mechanism,
      and injury intent. RESULTS: A total of 7,778 children had moderate or severe TBI
      with or without associated injuries. All races had similar demographics.
      Hispanics (n=1,041) had outcomes comparable to whites (n=4,762). Black children
      (n=1,238) had significantly increased premorbidities, penetrating trauma, and
      violent intent. They also had higher unadjusted mortality and longer mean
      intensive care unit and floor stays. After adjustment, there was no difference in
      the odds of death between black and white children. However, black patients were
      more likely to be discharged to an inpatient rehabilitation facility and had
      increased odds of possessing a functional deficit at discharge for all three
      domains studied. CONCLUSION: Black children with traumatic brain injury have
      worse clinical and functional outcomes at discharge when compared with
      equivalently injured white children.

PMID- 17495734
TI  - Pitfalls of implementing acute care surgery.
AB  - BACKGROUND: Incorporating emergency general surgery into the current practice of
      the trauma and critical care surgeon carries sweeping implications for future
      practice and training. METHODS: Herein, we examine the known benefits of the
      practice of emergency general surgery, contrast it with the emerging paradigm of
      acute care surgery, and examine pitfalls already encountered in integration of
      emergency general surgery into a traditional trauma/critical care surgery
      service. A MEDLINE literature search was supplemented with local experience and
      national presentations at major meetings to provide data for this review.
      RESULTS: Considerations including faculty complement, service structure, resident
      staffing, physician extenders, the decreased role of community hospitals in
      providing trauma and emergency general surgery care, and the effects on an
      elective operative schedule are inadequately explored at present. There are no
      firm recommendations as to how to incorporate emergency general surgery into a
      trauma/critical care practice that will satisfy both academic and community
      practice paradigms. CONCLUSIONS: The near future seems likely to embrace the
      expanded training and clinical care program termed acute care surgery. A host of
      essential elements have yet to be examined to undertake a critical analysis of
      the applicability, advisability, and appropriate structure of both emergency
      general surgery and acute care surgery in the United States. Proceeding along
      this pathway may be fraught with training, education, and implementation pitfalls
      that are ideally addressed before deploying acute care surgery as a national
      standard.

PMID- 17495735
TI  - Reconstruction of a post-traumatic infected bone defect of an open diaphyseal
      femur fracture by double LISS fixation: a case report.

PMID- 17495736
TI  - Reconstruction of open pelvic fracture skin defect with an anterolateral thigh
      island flap: a case report.

PMID- 17495737
TI  - Transient osteoporosis of pregnancy complicated by a pathologic subcapital hip
      fracture.

PMID- 17495738
TI  - Porta hepatis injury: a multidisciplinary approach.

PMID- 17495739
TI  - Traumatic orbital injury.

PMID- 17495740
TI  - Traumatic blindness after a displaced lateral orbital wall fracture.

PMID- 17495741
TI  - Muscle splitting approach with MetrX system for removal of intrathecal bullet
      fragment: a case report.

PMID- 17495742
TI  - Airway pressure release and biphasic intermittent positive airway pressure
      ventilation: are they ready for prime time?
AB  - Airway pressure release ventilation and biphasic positive airway pressure
      ventilation are being used increasingly as alternative strategies to conventional
      assist control ventilation for patients with acute respiratory distress syndrome
      (ARDS) and acute lung injury. By permitting spontaneous breathing throughout the
      ventilatory cycle, these modes offer several advantages over conventional
      strategies to improve the pathophysiology in these patients, including gas
      exchange, cardiovascular function, and reducing or eliminating the need for heavy
      sedation and paralysis. Whether these surrogate outcomes will translate into
      better patient outcomes remains to be determined. The purpose of this review is
      to summarize the rationale behind the use of these ventilatory strategies in
      ARDS, the clinical experience with the use of these modes, and their future
      applications in trauma patients.

PMID- 17495743
TI  - Myth or reality: hematocrit and hemoglobin differ in trauma.
AB  - BACKGROUND: Estimating blood loss in trauma patients usually involves the
      determination of hematocrit (Ht) or hemoglobin (Hb). However, in trauma patients,
      a poorly substantiated habit exists to determine both Ht and Hb in assessing
      acute blood loss. This suggests that Ht and Hb provide different information.
      Moreover, a survey of the literature showed a significant association of the
      subject trauma with the use of Ht. We investigated whether Ht and Hb differ in
      trauma patients. METHODS: Trauma patients with an Injury Severity Score>15
      admitted from 1996 to 2004 to the University Medical Center Groningen were
      analyzed. All blood samples obtained during the first 7 days postinjury in which
      both Ht and Hb were determined were studied. Ht and Hb were measured with a
      Coulter Counter. The relation between Ht and Hb was analyzed with linear
      regression. The potential effect of hemolysis was studied by analyzing lactate
      dehydrogenase levels. RESULTS: In 671 patients 2,461 paired Ht levels and Hb
      levels were obtained. The mean Ht was 30.9%+/-6.9% (interquartile range 25.8%
      35.8%). The mean concentration of Hb was 10.4+/-2.3 g/dL (interquartile range 8.7
      12.1 g/dL). Ht and Hb had a Pearson's R of 0.99 and the following relations
      applied: Ht (%)=2.953xHb (g/dL) or Hb (g/dL)=0.334xHt (%). Lactate dehydrogenase
      was not related with Ht and Hb, indicating hemolysis was not relevant.
      CONCLUSIONS: In a large series of trauma patients, Ht and Hb behaved as identical
      parameters. The idea that Ht is different from or even superior to Hb is a
      misconception. There is no reason for determining both Ht and Hb in trauma
      patients.

PMID- 17495744
TI  - Detection of viable autotransplanted splenic tissue by Tc-99m sulfur colloid.

PMID- 17495745
TI  - Cost effectiveness of using computed tomography (CT) for minor head injury
      compared with several other management strategies.

PMID- 17495746
TI  - High-frequency oscillatory ventilation (HFOV) in trauma patients.

PMID- 17495748
TI  - Use of a stent to treat a traumatic right renal artery injury.

PMID- 17495749
TI  - Use of laparoscopic forceps for removal of broken intramedullary locking screws.

PMID- 17495750
TI  - Report of preventable prehospital trauma deaths in a Greek health care region:
      importance of editorial comments.

PMID- 17495752
TI  - Results of blind subxyphoid pericardiotomy (BSP) for cardiac tamponade.

PMID- 17495754
TI  - Contribution of depression to cognitive impairment and dementia in older adults.
AB  - BACKGROUND: The objective of this review is to provide information for clinicians
      regarding current research and opinions on the association of depression to
      conditions of cognitive impairment and dementia. We also intend to integrate this
      current research and thinking into strategies for the assessment and treatment of
      depression in the context of cognitive impairment. REVIEW SUMMARY: Depression is
      highly prevalent in mild cognitive impairment and most dementias. It may be a
      risk factor for the subsequent development of dementia and in some conditions may
      be a prodromal symptom. It is important to detect and effectively treat
      depression because the comorbidity of depression and cognitive impairment is
      associated with greater cognitive and functional decline and higher rates of
      institutionalization. Depression often can be differentiated from Alzheimer
      disease and other dementias based on characteristics of clinical history and
      presentation. Screening of depression and cognitive impairment will help
      characterize the presence and severity of these conditions, but limitations in
      screening approaches may necessitate comprehensive assessment in complex cases
      where differential diagnosis is important to treatment planning. CONCLUSION:
      Although depression and cognitive impairment are important issues in the
      treatment of older adults, there are particular risks when they occur together.
      Appropriate assessment and screening can help guide the clinician to appropriate
      and timely interventions. Pharmacologic and nonpharmacologic treatment approaches
      are both efficacious in reducing depression in cognitive impairment and dementia.

PMID- 17495755
TI  - Migraine aura.
AB  - Recurrent episodes of transient focal neurologic symptoms, known as aura, occur
      in association with migraine headache in about 11.9 million people in the United
      States. At present, the International Headache Society has recognized 3 "typical"
      auras: visual, sensory, and language. Increasing evidence from investigations in
      human subjects suggests that typical auras may be the clinical manifestation of a
      cortical spreading depression (CSD)-like phenomenon. Other studies have shown
      altered reactivity and processing within the cortices of migraineurs who
      experience an aura, which might render them more vulnerable to CSD-like events.
      Recent investigations also support the hypothesis that events intrinsic to the
      cerebral cortex are capable of activating trigeminal nociceptive neurons and of
      affecting the caliber of vascular structures innervated by them. A better
      understanding of the mechanisms underlying the aura may potentially lead to more
      effective therapies, which will aim at preventing migraine headaches before they
      start.

PMID- 17495756
TI  - Advances in the pharmacologic management of early Parkinson disease.
AB  - BACKGROUND: Levodopa, in combination with a dopa decarboxylase inhibitor,
      provides the greatest symptomatic benefit with the fewest short-term side effects
      in the treatment of Parkinson disease (PD). However, the disease continues to
      progress, and the long-term use of levodopa is associated with the development of
      motor fluctuations and dyskinesias. REVIEW SUMMARY: Alternatives to the use of
      levodopa in early PD include monoamine oxidase B (MAO-B) inhibitors, dopamine
      agonists, and amantadine. Although no medication has been proven to slow the
      progression of Parkinson disease, preclinical studies have demonstrated
      neuroprotective effects of MAO-B inhibitors, and a recent study of rasagiline
      found that PD patients treated with rasagiline for 12 months experienced less
      progression of symptoms than patients treated with placebo for 6 months followed
      by rasagiline for 6 months. Several clinical trials have demonstrated that the
      initial use of a dopamine agonist to which levodopa can be added is associated
      with fewer motor complications than treatment with levodopa alone. In addition,
      preclinical studies suggest that adjunctive use of the catechol-O
      methyltransferase (COMT) inhibitor entacapone when levodopa is first introduced
      may be associated with fewer motor complications than treatment with levodopa
      alone. CONCLUSION: Treatment of early PD with an MAO-B inhibitor, dopamine
      agonist, or amantadine, may provide useful alternatives to treatment with
      levodopa. Adding entacapone at the initiation of levodopa therapy may reduce the
      development of motor complications. Long-term studies are required to evaluate
      the potential long-term benefits of these treatment strategies.

PMID- 17495757
TI  - A new look at the second-generation antiepileptic drugs: a decade of experience.
AB  - OBJECTIVE: To review data from the literature regarding the efficacy and
      tolerability of the second-generation antiepileptic drugs which were approved by
      the Food and Drug Administration (FDA) since 1994. METHODS: A MEDLINE search of
      the literature, as well as review of bibliographies, was performed to identify
      randomized controlled trials and other reports evaluating efficacy,
      pharmacokinetic profile, adverse effects, and drug interactions of the second
      generation antiepileptic drugs. Key search terms included felbamate, gabapentin,
      lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, zonisamide, and
      pregabalin. RESULTS: Each of the second-generation antiepileptic drugs has
      demonstrated statistically significant reductions in seizure frequency over
      baseline compared with placebo or active control. Limited studies of efficacy of
      the new agents compared with the traditional antiepileptic drugs found no
      significant differences. Each of the second-generation antiepileptic drugs has a
      unique pharmacokinetic and side-effect profile. Compared with the traditional
      agents, the second-generation antiepileptic drugs have fewer serious adverse
      effects, as well as drug interactions. CONCLUSION: Knowledge of the second
      generation antiepileptic drugs has greatly expanded over the past decade. The
      newer agents offer many options in the treatment of epilepsy that are safe,
      efficacious, and well tolerated.

PMID- 17495758
TI  - Autoimmune encephalopathies.
AB  - BACKGROUND: Evaluation of patients with recent onset of progressive cognitive and
      behavioral problems can be challenging. Psychiatric disorders, metabolic
      derangements, toxins and infections are generally considered in the differential
      diagnosis along with prion disorders (Creutzfeldt-Jakob disease) and rapidly
      progressive degenerative dementias. Some subacute encephalopathies are caused by
      autoimmune or inflammatory mechanisms, recognized by the association with
      autoantibody markers and/or clear response to immunomodulatory treatment. This
      review describes the clinical features of these potentially reversible autoimmune
      encephalopathies. REVIEW SUMMARY: Morvan syndrome, paraneoplastic limbic
      encephalitis (PLE), and nonparaneoplastic autoimmune limbic encephalitis have
      characteristic clinical and serological features. Limbic encephalitis is
      characterized by short-term memory impairment, complex partial temporal lobe
      seizures and psychiatric symptoms. Signal abnormalities in the mesial temporal
      lobes without contrast enhancement are the typical MRI findings. Morvan syndrome
      presents with behavioral changes, hallucinations, severe insomnia, autonomic
      hyperactivity and neuromyotonia (spontaneous muscle activity). Corticosteroid
      responsive encephalopathy associated with evidence of thyroid autoimmunity
      (sometimes called Hashimoto encephalopathy) has a broad range of clinical
      presentation. Cognitive impairment with tremor, seizures, stroke-like events
      (including transient aphasia) and normal thyroid hormone levels is a common
      scenario. In the absence of diagnostic serological findings, clinical improvement
      with corticosteroids may be the only evidence of autoimmune encephalopathy.
      CONCLUSIONS: Autoimmune encephalopathies are an important cause of rapidly
      progressive cognitive and behavioral decline that probably remain under
      recognized. Electroencephalography, brain MRI, cerebrospinal fluid examination
      and serological tests are useful diagnostic tools. With increased clinical
      suspicion, these diseases may be diagnosed and treated successfully.

PMID- 17495759
TI  - Simultaneous onset of hemorrhagic and ischemic strokes.
AB  - Primary brain hemorrhage and infarction only very rarely occur simultaneously. We
      report a patient with the simultaneous onset of hemorrhagic and ischemic strokes
      who had uncontrolled hypertension and atrial fibrillation. Neuroradiologic
      investigations revealed a large right thalamic hematoma with ventricular
      extension and an infarct in the territory of the left internal carotid artery.
      The patient died at the end of the second day because of herniation in spite of
      anti-edema and antihypertensive medication.

PMID- 17495760
TI  - Lymphomatosis cerebri presenting as rapidly progressive dementia.
AB  - BACKGROUND: As the population ages, the incidence of dementing illness is
      increasing. Accurate and timely diagnosis provides the best hope for instituting
      appropriate treatment and educating the patient and family members as to
      prognosis based upon likely etiology in a given patient. REVIEW SUMMARY: We
      present a case of an elderly patient referred to our tertiary-care center for
      further evaluation of a rapidly progressive dementia, whose definitive diagnosis
      was delayed by nonspecific MRI findings, presence of 14-3-3 protein in the CSF,
      and nonspecific cutaneous lesions. At brain biopsy, he was thought to have a
      diffusely infiltrating lymphoma, with distinctive immunohistochemical features.
      CONCLUSION: This case is notable in that it presents a patient with progressive
      dementia whose diagnosis of primary central nervous system lymphoma (PCNSL) was
      delayed because of the lymphoma's atypical diffusely infiltrating nature.
      Awareness of this unique presentation may hasten the time between clinical
      presentation, diagnosis, and subsequent treatment.

PMID- 17495761
TI  - Multiple sclerosis-like clinical and magnetic resonance imaging findings in human
      immunodeficiency virus positive-case.
AB  - OBJECTIVE: Neurologic complications may develop during the course of acquired
      immunodeficiency syndrome. Differential diagnosis of the chronic progressive
      myelopathy related to human immunodeficiency virus must include multiple
      sclerosis. CASE REPORT: We report a human immunodeficiency virus-positive case
      with progressive myelopathy who showed multiple sclerosis-like white matter
      lesions on cranial magnetic resonance imaging. Viral screening revealed positive
      serology for human immunodeficiency virus. CONCLUSION: This case suggests that in
      a patient who presents with a multiple sclerosis-like clinical course and
      cerebral white matter lesions, a human immunodeficiency virus-related clinical
      picture should be taken into consideration in the differential diagnosis.

PMID- 17495762
TI  - Locked-in syndrome due to invasive fungal rhinosinusitis in an immunosuppressed
      patient.
AB  - BACKGROUND: The locked-in syndrome is typically caused by basilar artery
      thrombosis, resulting in ventral pontine infarction. Infectious basilar arteritis
      is a rare alternative etiology. CASE SUMMARY: We present a 24-year-old female
      with a prodrome of facial pain without fever or meningismus, who developed a
      locked-in syndrome due to an invasive fungal infection after bone marrow
      transplantation. The clinical course and neuroimaging demonstrating sinusitis
      with adjacent pontine infarction but without basilar artery thrombosis are
      presented. The infectious differential diagnosis and management of invasive
      fungal infection are discussed. CONCLUSION: Facial pain without fever or
      meningismus may be an early symptom of invasive fungal rhinosinusitis, which may
      involve small basilar pontine perforating arteries, leading to a locked-in
      syndrome in immunosuppressed patients. Early recognition and treatment may
      prevent life-threatening neurologic complications.

PMID- 17495763
TI  - Saccadic ping pong gaze in coma.
AB  - In this report, we describe the peculiar eye movements of a young man who became
      comatose after a head injury. The eyes moved rhythmically from one side to
      another, without pausing in the lateral positions. This phenomenon has been
      described as "ping pong gaze" (PPG), referring to short-cycling periodic
      alternating gaze with smooth eye deviations. In the present patient, however, a
      saccadic type of PPG could be confirmed by oculography. Possible clinical and
      pathophysiological implications are discussed.

PMID- 17495764
TI  - Alpha-lipoic acid may improve symptomatic diabetic polyneuropathy.
AB  - OBJECTIVE: In patients with symptomatic diabetic polyneuropathy, is oral alpha
      lipoic acid (ALA) effective in improving neuropathic symptoms compared with
      placebo? METHODS: The question was addressed with a structured evidence-based
      clinical neurologic practice review via videoconferencing between 3 academic
      institutions. Participants included consultant and resident neurologists,
      clinical epidemiologists, medical librarians, and clinical content experts. A
      critically appraised topic format was employed, with a clinical scenario,
      structured question, search strategy, appraisal, results, summary of evidence,
      commentary, and bottom-line conclusions. RESULTS: A single modestly valid
      randomized controlled trial demonstrated that oral ALA in doses of 600 mg, 1200
      mg, and 1800 mg was effective in reducing neuropathic symptoms of diabetic distal
      symmetric polyneuropathy (DSP) at 5 weeks, as assessed by the Total Symptom Score
      (>or=50% reduction), with number needed to treat (NNT) (95% CI) of 2.7 (1.8 to
      5.8), 4.1 (2.3 to 20.2), and 3.2 (2.0 to 8.6), respectively. Adverse events,
      including nausea, vomiting, and vertigo, were identified but occurred most
      frequently with ALA doses of 1200 mg and 1800 mg. Overall, treatment emergent
      adverse events for ALA 600 mg were not significantly different than placebo, but
      ALA 1200 mg and 1800 mg had number needed to harm (95% CI) of 4.5 (2.4 to 31.0)
      and 3.0 (1.9 to 7.1), respectively. CONCLUSION: Oral ALA may improve neuropathic
      symptoms in diabetic DSP. A single modestly valid RCT demonstrated that 600 mg
      was an effective and well-tolerated dose, with NNT 2.7 to significantly reduce
      neuropathic pain symptoms over a 5-week period. ALA's role and place in an
      algorithm among other commonly prescribed oral treatments for symptomatic relief
      of neuropathic pain in diabetic DSP remains unclear.

PMID- 17495765
TI  - Stroke prevention.

PMID- 17495766
TI  - Biomechanical testing simulation of a cadaver spine specimen: development and
      evaluation study.
AB  - STUDY DESIGN: This article describes a computer model of the cadaver cervical
      spine specimen and virtual biomechanical testing. OBJECTIVES: To develop a
      graphics-oriented, multibody model of a cadaver cervical spine and to build a
      virtual laboratory simulator for the biomechanical testing using physics-based
      dynamic simulation techniques. SUMMARY OF BACKGROUND DATA: Physics-based computer
      simulations apply the laws of physics to solid bodies with defined material
      properties. This technique can be used to create a virtual simulator for the
      biomechanical testing of a human cadaver spine. An accurate virtual model and
      simulation would complement tissue-based in vitro studies by providing a
      consistent test bed with minimal variability and by reducing cost. METHOD: The
      geometry of cervical vertebrae was created from computed tomography images.
      Joints linking adjacent vertebrae were modeled as a triple-joint complex,
      comprised of intervertebral disc joints in the anterior region, 2 facet joints in
      the posterior region, and the surrounding ligament structure. A virtual
      laboratory simulation of an in vitro testing protocol was performed to evaluate
      the model responses during flexion, extension, and lateral bending. RESULTS: For
      kinematic evaluation, the rotation of motion segment unit, coupling behaviors,
      and 3-dimensional helical axes of motion were analyzed. The simulation results
      were in correlation with the findings of in vitro tests and published data. For
      kinetic evaluation, the forces of the intervertebral discs and facet joints of
      each segment were determined and visually animated. CONCLUSIONS: This methodology
      produced a realistic visualization of in vitro experiment, and allowed for the
      analyses of the kinematics and kinetics of the cadaver cervical spine. With
      graphical illustrations and animation features, this modeling technique has
      provided vivid and intuitive information.

PMID- 17495767
TI  - Immunohistochemical demonstration of advanced glycation end products and the
      effects of advanced glycation end products in ossified ligament tissues in vitro.
AB  - STUDY DESIGN: This study correlates advanced glycation end products with ossified
      ligament tissues of the cervical spine in vitro. OBJECTIVE: To investigate the
      effect of advanced glycation end products on ossification of the spinal ligaments
      in vitro. SUMMARY OF BACKGROUND DATA: We have hypothesized that an accumulation
      of advanced glycation end products in the spinal ligament might result in some
      observable change in specific growth factors responsible for ossification in the
      spinal ligaments. METHODS: Samples of the posterior longitudinal and yellow
      ligaments were harvested from patients (n = 5) with ossification of the posterior
      longitudinal ligament, and analyzed for the presence of advanced glycation end
      products and their receptor advanced glycation end product receptor by
      immunohistochemistry. Real-time polymerase chain reaction (PCR) was used to
      quantify the messenger ribonucleic acid (mRNA) levels of bone morphogenetic
      protein (BMP)-2, BMP-7, alkaline phosphatase, an osteoblast-specific
      transcription factor 1 (Cbfa1), and osteocalcin from yellow ligament cells
      treated with advanced glycation end products. RESULTS: Immunohistochemical
      analysis revealed that advanced glycation end products and advanced glycation end
      product receptor were localized to within the posterior longitudinal and yellow
      ligaments. Advanced glycation end products were found to increase significantly
      the expression of BMP-2, BMP-7, Cbfa1, and osteocalcin at the mRNA levels after
      treatment with advanced glycation end products (1 microg/mL). CONCLUSIONS: This
      is the first report to investigate the correlation, if any, between the ossified
      spinal ligament and advanced glycation end products. These results suggested that
      accumulation in advanced glycation end products and their interaction with
      advanced glycation end product receptor were 1 of the important risk factors in
      the process of ossification in the spinal ligaments.

PMID- 17495768
TI  - Lumbar ligamentum flavum hypertrophy is due to accumulation of inflammation
      related scar tissue.
AB  - STUDY DESIGN: A histologic, biologic, and immunohistochemical assessment using
      human samples of the lumbar ligamentum flavum. OBJECTIVE: To prove our hypothesis
      that hypertrophy of the ligamentum flavum is caused by accumulation of
      inflammation-related scar tissue. SUMMARY OF BACKGROUND DATA: Lumbar spinal canal
      stenosis is 1 of the most common spinal disorders in elderly patients. Canal
      narrowing, in part, results from hypertrophy of the ligamentum flavum. The
      hypertrophy mechanism remains unclear. Based on our preliminary analyses, we have
      previously proposed that the hypertrophy may be due to accumulation of scar
      tissue in the ligament. Scar tissue is reported to develop after inflammation;
      however, there is no report, including our previous study, on inflammation in the
      ligamentum flavum. There is a need for an in-depth investigation of any
      relationship between inflammation and scar formation in the ligamentum flavum. If
      inflammation is related to hypertrophy, we may control/delay the hypertrophy by
      inhibiting the inflammation. METHODS: Twenty-one ligamentum flavum samples were
      obtained for the histologic study. Trichrome and Verhoeff-van Gieson stains were
      used to assess the degree of fibrosis (scarring) and content of elastic fibers,
      respectively. Two ligamentum flavum samples, hypertrophied and thin control
      ligaments, were used for a global genetic assessment by oligonucleotide gene
      array technology with gene chips. Messenger ribonucleic acid expression of
      cyclooxygenase (COX)-2 was quantitatively measured from 16 ligamentum flavum
      samples using real-time reverse transcriptase polymerase chain reaction.
      Immunohistochemistry evaluated the cellular location of COX-2 in ligamentum
      flavum. RESULTS: In the hypertrophied ligament, severe fibrosis (scarring) was
      observed in the entire area of the ligamentum flavum, and the severity of
      scarring showed a significant (r = 0.79; P < 0.0001) and positive linear
      correlation with ligamentum flavum thickness. Gene array results showed in both
      thin/control and hypertrophied ligaments expression of inflammation-related genes
      such as COX-2, tumor necrosis factor-alpha, and interleukin-1, 6, 8, and 15. Real
      time polymerase chain reaction showed COX-2 messenger ribonucleic acid expression
      in all ligamentum flavum samples. Its expression showed weak positive linear
      correlation with the thickness of ligament. COX-2 was released from vascular
      endothelial cells in ligamentum flavum as per the immunohistochemical analysis.
      CONCLUSIONS: Accumulation of fibrosis (scarring) causes hypertrophy of the
      ligamentum flavum. Inflammation-related gene expression is found in the
      ligamentum flavum. It might be possible to prevent the hypertrophy of ligamentum
      flavum with antiinflammatory drugs.

PMID- 17495770
TI  - Results of the prospective, randomized, multicenter Food and Drug Administration
      investigational device exemption study of the ProDisc-L total disc replacement
      versus circumferential fusion for the treatment of 1-level degenerative disc
      disease.
AB  - STUDY DESIGN: A prospective, randomized, multicenter, Food and Drug
      Administration-regulated Investigational Device Exemption clinical trial.
      OBJECTIVE: To evaluate the safety and effectiveness of the ProDisc-L (Synthes
      Spine, West Chester, PA) lumbar total disc replacement compared to
      circumferential spinal fusion for the treatment of discogenic pain at 1 vertebral
      level between L3 and S1. SUMMARY OF BACKGROUND DATA: As part of the
      Investigational Device Exemption clinical trial, favorable single center results
      of lumbar total disc replacement with the ProDisc-L have been reported
      previously. METHODS: Two hundred eighty-six (286) patients were treated on
      protocol. Patients were evaluated before and after surgery, at 6 weeks, 3, 6, 12,
      18, and 24 months. Evaluation at each visit included patient self-assessments,
      physical and neurologic examinations, and radiographic evaluation. RESULTS:
      Safety of ProDisc-L implantation was demonstrated with 0% major complications. At
      24 months, 91.8% of investigational and 84.5% of control patients reported
      improvement in the Oswestry Low Back Pain Disability Questionnaire (Oswestry
      Disability Index [ODI]) from preoperative levels, and 77.2% of investigational
      and 64.8% of control patients met the > or =15% Oswestry Disability Index
      improvement criteria. Overall neurologic success in the investigational group was
      superior to the control group (91.2% investigational and 81.4% control; P =
      0.0341). At 6 weeks and 3 months follow-up time points, the ProDisc-L patients
      recorded SF-36 Health Survey scores significantly higher than the control group
      (P = 0.018, P = 0.0036, respectively). The visual analog scale pain assessment
      showed statistically significant improvement from preoperative levels regardless
      of treatment (P < 0.0001). Visual analog scale patient satisfaction at 24 months
      showed a statistically significant difference favoring investigational patients
      over the control group (P = 0.015). Radiographic range of motion was maintained
      within a normal functional range in 93.7% of investigational patients and
      averaged 7.7 degrees. CONCLUSIONS: ProDisc-L has been found to be safe and
      efficacious. In properly chosen patients, ProDisc-L has been shown to be superior
      to circumferential fusion by multiple clinical criteria.

PMID- 17495772
TI  - Brain-derived neurotrophic factor gene transfer with adeno-associated viral and
      lentiviral vectors prevents rubrospinal neuronal atrophy and stimulates
      regeneration-associated gene expression after acute cervical spinal cord injury.
AB  - STUDY DESIGN: Experimental animal study. OBJECTIVE: To determine if viral vectors
      carrying the gene for brain-derived neurotrophic factor (BDNF) could be used to
      promote an axonal regenerative response in rubrospinal neurons after an acute
      cervical spinal cord injury. SUMMARY OF BACKGROUND DATA: Following axotomy in the
      cervical spinal cord, rubrospinal neurons undergo severe atrophy and fail to up
      regulate important genes for regeneration. This can be attenuated or reversed
      with the infusion of BDNF to the injured cell bodies. This infusion technique,
      however, causes substantial parenchymal damage around the red nucleus and is
      limited by occlusion of the infusion pumps. This study examined whether viral
      vectors could be used to deliver the BDNF gene in a less damaging fashion and
      whether this could promote a regenerative response in injured rubrospinal
      neurons. METHODS: Following a cervical spinal cord injury, the viral vectors were
      injected into the vicinity of the injured red nucleus. The extent of parenchymal
      damage around the red nucleus was assessed, as was the immunoreactivity to BDNF
      and cellular transfection patterns. Rubrospinal neuronal cross-sectional area was
      measured to determine if atrophy had been reversed, and in situ hybridization for
      GAP-43 and Talpha1 tubulin was performed to determine if there genes, which are
      important for axonal regeneration, were up-regulated. RESULTS: Parenchymal damage
      associated with viral injection was significantly less than with previous
      infusion techniques. BDNF immunoreactivity around the red nucleus indicated that
      the BDNF transgene was expressed. Both viral vectors reversed rubrospinal
      neuronal atrophy and promoted the expression of GAP-43 and Talpha1 tubulin.
      CONCLUSIONS: Viral-mediated transfer of the BDNF gene was successful at promoting
      a regenerative response in rubrospinal neurons following acute cervical spinal
      cord injury, with significantly less parenchymal damage than previously observed
      when infusing the BDNF protein.

PMID- 17495773
TI  - The in vivo biological effects of intradiscal recombinant human bone
      morphogenetic protein-2 on the injured intervertebral disc: an animal experiment.
AB  - STUDY DESIGN: Prospective analysis. OBJECTIVE: To investigate biologic influences
      of recombinant human bone morphogenetic protein (rhBMP)-2 on intervertebral discs
      after anular tears. SUMMARY OF BACKGROUND DATA: Treatments for intervertebral
      disc injury or degeneration are unsatisfactory. rhBMP-2, a high-potency
      osteoinductive and chondroinductive substance, is approved for use in anterior
      lumbar interbody fusions. rhBMP-2 stimulates the proliferation of rat disc cells
      and the secretion of extracellular matrix in vitro. In vivo responses in the
      intervertebral disc after anular tears are rarely studied. METHODS: Twenty New
      Zealand white rabbits received full-thickness anular tears and intradiscal
      injections of saline (control) and rhBMP-2 0.1 mg with and without coral grafts
      at L2-L3, L3-L4, and L4-L5, respectively. Three died or had infection. Therefore,
      17 underwent radiography and sacrifice at 12 weeks. Spinal sections were stained
      with hematoxylin and eosin to examine responses to rhBMP-2. RESULTS: Radiographs
      revealed degenerative changes, such as disc space narrowing and irregularity,
      subchondral sclerosis, osteophyte formation, and hypertrophy of vertebral
      endplates in all groups. Degeneration was more frequent and severe with rhBMP-2
      with (P < 0.01) and without (P < 0.05) coral than with saline. Two rabbits
      receiving rhBMP-2 and coral achieved solid interbody bony fusion. New bone
      formation was noted in 2 controls, in 3 animals treated with rhBMP-2, and in 4
      treated with rhBMP-2 and coral. Vascularity and fibroblast proliferation
      increased with rhBMP-2 (n = 14) and rhBMP-2 with coral (n = 9) compared with
      control (n = 3; P < 0.01 and P = 0.03, respectively). Inflammatory infiltrates
      increased with rhBMP-2 (n = 8) compared with control (n = 2; P = 0.03).
      CONCLUSIONS: Degenerative changes were more frequent and severe in the groups
      treated with rhBMP-2 with or without coral in radiographic findings. In
      histopathologic findings, rhBMP-2 promoted hypervascularity and fibroblast
      proliferation of the intervertebral disc after an anular tear.

PMID- 17495774
TI  - Microarray analysis of laser capture microdissected-anulus cells from the human
      intervertebral disc.
AB  - STUDY DESIGN: Five Thompson Grade I/II discs (Group 1), 7 Grade III discs (Group
      2), and 3 Grade IV discs (Group IV) were studied here in a project approved by
      the authors' Human Subjects Institutional Review Board. OBJECTIVES: Our objective
      was to use laser capture microdissection (LCM) to harvest cells from the human
      anulus and to derive gene expression profiles using microarray analysis. SUMMARY
      OF BACKGROUND DATA: Appropriate gene expression is essential in the
      intervertebral disc for maintenance of extracellular matrix (ECM), ECM
      remodeling, and maintenance of a viable disc cell population. During disc
      degeneration, cell numbers drop, making gene expression studies challenging.
      METHODS: LCM was used to harvest cells from paraffin-embedded sections of human
      anulus tissue. Gene profiling used Affymetrix GeneChip Human X3P arrays. ANOVA
      and SAM permutation analysis were applied to dCHIP normalized, filtered, and log
      transformed gene expression data ( approximately 33,500 probes), and data
      analyzed to identify genes that were significantly differentially expressed
      between the 3 groups. RESULTS: We identified 47 genes that were significantly
      differentially expressed between the 3 groups (P < 0.001 and lowest q values).
      Compared with the healthiest discs (Grade I/II), 13 genes were up-regulated and
      19 down-regulated in both the Grade III and the Grade IV discs. Genes with
      biologic significance regulated during degeneration involved cell senescence, low
      cell division rates, hypoxia-related genes, heat-shock protein 70 interacting
      protein, neuropilin 2, and interleukin-23p19 (interleukin-12 family).
      CONCLUSIONS: Results expand our understanding of disc aging and degeneration and
      show that LCM is a valuable technique that can be used to collect mRNA amounts
      adequate for microarray analysis from the sparse cell population of the human
      anulus.

PMID- 17495775
TI  - Nucleus pulposus cellular longevity by telomerase gene therapy.
AB  - STUDY DESIGN: Nonviral transfection of nucleus pulposus cells with a telomerase
      expression construct to assess the effects on cellular lifespan, function,
      karyotypic stability, and transformation properties. OBJECTIVES: To investigate
      whether telomerase gene therapy can extend the cellular lifespan while retaining
      functionality of nucleus pulposus cells in a safe manner. SUMMARY OF BACKGROUND
      DATA: Degeneration of the intervertebral disc is an age-related condition in
      which cells responsible for the maintenance and health of the disc deteriorate
      with age. Telomerase can extend the cellular lifespan and function of other
      musculoskeletal tissues, such as the heart, bones, and connective tissues.
      Therefore, extension of the cellular lifespan and matrix production of
      intervertebral disc cells may have the potential to delay the degeneration
      process. METHODS: Ovine nucleus pulposus cells were lipofectamine transfected in
      vitro with a human telomerase reverse transcriptase (hTERT) expression construct.
      Cellular lifespan and matrix transcript levels were determined by cumulative
      population doublings and real-time RT-PCR, respectively. G1-cell cycle
      checkpoint, p53 functionality, growth of transfected cells in anchorage
      independent or serum starvation conditions, and karyotypic analysis were
      performed. RESULTS: Transfection was achieved successfully with 340% +/- 7% (mean
      +/- SD) relative telomerase activity in hTERT-transfected cells. hTERT
      transfection enabled a 50% extension in mean cellular lifespan and prolonged
      matrix production of collagen 1 and 2 for more than 282 days. Karyotypic
      instability was detected but G1-cell cycle checkpoint and p53 was functionally
      comparable to parental cells with no growth in serum starvation or anchorage
      independent conditions. CONCLUSIONS: Telomerase can extend the cellular lifespan
      of nucleus pulposus cells and prolong the production of extracellular matrix.
      Safety is still unresolved, as karyotypic instability was detected but no loss of
      contact inhibition, mitogen dependency, or G1-cell cycle checkpoint control was
      evident.

PMID- 17495776
TI  - Restoration of disc height loss by recombinant human osteogenic protein-1
      injection into intervertebral discs undergoing degeneration induced by an
      intradiscal injection of chondroitinase ABC.
AB  - STUDY DESIGN: In vivo study of the effect of an injection of recombinant human
      osteogenic protein-1 into degenerated discs induced by chondroitinase ABC.
      OBJECTIVE: To investigate the efficacy of an injection of recombinant human
      osteogenic protein-1 to induce the recovery of disc height, and biochemical and
      histologic repair, in discs degenerated through enzymatic digestion by
      chondroitinase ABC. SUMMARY OF THE BACKGROUND DATA: Chondroitinase ABC is
      currently proposed as a chemonucleolysis agent; however, postchemonucleolysis
      degeneration is currently unavoidable. Recombinant human OP-1 has been shown to
      promote extracellular matrix repair in vitro and in vivo. METHODS: Fifty-four
      adolescent New Zealand white rabbits were used. Four weeks after an initial
      injection of chondroitinase ABC (10 mU/disc), 5% lactose (10 microL/disc) or
      recombinant human osteogenic protein-1 (100 microg in 10 microL lactose/disc) was
      injected. Disc heights were monitored radiographically at 2-week intervals, and
      rabbits were killed at 6, 8, 12, and 16 weeks after the initial chondroitinase
      ABC injections. The intervertebral discs were subjected to histologic and
      biochemical analyses. RESULTS: Significant disc space narrowing was observed in
      both groups 2 weeks after the injection of chondroitinase ABC. In the
      chondroitinase ABC/lactose group, this narrowing progressed after the vehicle
      injection and was sustained for up to 16 weeks. In the chondroitinase
      ABC/recombinant human osteogenic protein-1 group, the disc height index showed a
      significant increase at 6 weeks (lactose vs. recombinant human osteogenic protein
      1; P < 0.01); this recovery was sustained for up to 16 weeks. The proteoglycan
      content was higher in the chondroitinase ABC/recombinant human osteogenic protein
      1 group than in the chondroitinase ABC/lactose group. However, histologic
      changes, after the recombinant human osteogenic protein-1 injection, were not
      observed. CONCLUSIONS: A single injection of recombinant human osteogenic protein
      1 into a rabbit disc dramatically reversed the decrease in disc height induced by
      chondroitinase ABC chemonucleolysis. The recovery was significant and sustained
      over the next 12 weeks. The therapeutic effects of both chondroitinase ABC
      chemonucleolysis and recombinant human osteogenic protein-1 injections should be
      further explored in higher animals before it is applied to humans.

PMID- 17495777
TI  - rhBMP-2 (ACS and CRM formulations) overcomes pseudarthrosis in a New Zealand
      white rabbit posterolateral fusion model.
AB  - STUDY DESIGN: The study design consisted of a New Zealand white rabbit model of
      pseudarthrosis repair. Study groups consisting of no graft, autograft, or
      recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen
      sponge (ACS) or compression resistant matrix (CRM) were evaluated. OBJECTIVE: To
      evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM).
      SUMMARY OF BACKGROUND DATA: rhBMP-2 has been shown to have a 100% fusion rate in
      a primary rabbit fusion model, even in the presence of nicotine, which is known
      to inhibit fusion. METHODS: Seventy-two New Zealand white rabbits underwent
      posterolateral lumbar fusion with iliac crest autograft. To establish
      pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines
      were explored and all pseudarthroses were redecorticated and implanted with no
      graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed
      by manual palpation and histology. RESULTS: Eight rabbits (11%) were lost to
      complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted
      pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17
      autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%).
      Histologic analysis demonstrated more mature bone formation in the rhBMP-2
      groups. CONCLUSIONS: The 2 rhBMP-2 formulations led to significantly higher
      fusion rates and histologic bone formation than no graft and autograft controls
      in this pseudarthrosis repair model.

PMID- 17495778
TI  - The load-sharing classification of thoracolumbar fractures: an in vitro
      biomechanical validation.
AB  - STUDY DESIGN: An in vitro biomechanical investigation. OBJECTIVES: The purpose of
      this study was to investigate the association between various load-sharing score
      and the acute flexibility of thoracolumbar fractures by measuring the 3
      dimensional flexibility data. SUMMARY OF BACKGROUND DATA: The load-sharing
      classification is a way to describe the injury severity of a spinal fracture and
      can be very useful in determining successful candidates for the choice of
      operative approaches. However, this classification needs to be validated by
      biomechanical and more clinical studies before its widespread use. To date, no
      biomechanical study was available. METHODS: Eighteen fresh bovine T12-L3
      specimens were harvested and divided into 3 groups, and subjected to axial
      compressive impact with 63.8, 107.8, and 137.2 J energy, respectively. Radiograph
      films and computed tomography scans of the experimental spine were taken in
      neutral posture after trauma. Multidirectional flexibility of each specimen was
      measured under flexion-extension, right/left lateral bending, and right/left
      axial rotation before and after trauma. The association between the
      multidirectional instabilities and the vertebral injuries to each of load-sharing
      point score was analyzed. RESULTS: The load-sharing score of a fracture increased
      with the level of impact energy. Significant positive correlations were found
      between the load-sharing score and the motion parameters (average R = 0.434,
      average P = 0.004). Fractures with mild comminution (< or =6 points) showed more
      stability as compared to those with more comminution (> or =7 points) (P < or =
      0.016). CONCLUSION: This study confirms that assessing the load-sharing score
      should be helpful in evaluating the acute instability of thoracolumbar fractures,
      and justifies the use of load-sharing classification in the thoracolumbar
      fractures.

PMID- 17495779
TI  - Biomechanical comparison of instrumented and uninstrumented multilevel cervical
      discectomy versus corpectomy.
AB  - STUDY DESIGN: In vitro flexibility test comparing biomechanics of cervical
      corpectomy versus discectomy with and without instrumentation. OBJECTIVES: To
      evaluate whether the additional effort required to perform multilevel
      discectomies instead of corpectomies is worthwhile biomechanically. SUMMARY OF
      BACKGROUND DATA: Both cervical corpectomy and discectomy have been shown to be
      effective clinically. No previous biomechanical comparison exists. METHODS:
      Fourteen human cadaveric cervical spines were studied: 1) intact, 2) after
      discectomy and wedge grafting at C4-C5, C5-C6, and C6-C7 (Group 1) or corpectomy
      and strut grafting of C5 and C6 (Group 2), 3) after attaching a locking metal
      plate from C4-C7, and 4) after adding posterior locking lateral mass screw/rod
      instrumentation across C4-C7. Non-constraining, nondestructive torques induced
      flexion, extension, lateral bending, and axial rotation (maximum, 1.5 Nm) while
      angular motion was measured stereophotogrammetrically. RESULTS: Discectomy and
      grafting did not alter the range of motion (ROM) significantly from normal during
      any loading mode (P > 0.11). Corpectomy and grafting allowed a significantly
      greater range of motion than normal during flexion, lateral bending, and axial
      rotation (P < 0.05). Addition of an anterior plate reduced ROM to significantly
      less than normal during all loading modes in both groups (P < 0.005). Addition of
      posterior instrumentation further reduced ROM significantly in both groups (P <
      0.01). There was no significant difference in ROM between corpectomy and
      discectomy groups in any loading mode whether uninstrumented (P > 0.18),
      anteriorly plated (P > 0.33), or anteriorly and posteriorly instrumented (P >
      0.30). CONCLUSIONS: Less difference in stability was observed than was predicted
      between specimens receiving multilevel discectomy versus multilevel corpectomy,
      regardless of whether specimens were left unplated, plated anteriorly, or fixated
      with combined anterior/posterior instrumentation.

PMID- 17495780
TI  - Natural history of progressive adult scoliosis.
AB  - STUDY DESIGN: A retrospective analysis of the progression of adult scoliosis.
      OBJECTIVE: To establish an individual prognosis. SUMMARY OF BACKGROUND DATA: Most
      studies have investigated the adolescent scoliosis after skeletal maturity, but
      the results are discordant. METHODS: Two senior physicians measured all the
      radiographs of 51 adults who had a progressive scoliosis. The mean delay between
      the first and last radiograph was 27 years. For each patient, a diagram was
      established with the Cobb angle on the y-axis and the corresponding age on the x
      axis. We noted the age and Cobb angle of the first radiograph showing a rotatory
      subluxation and the age of menopause. We used linear regression and the analysis
      of variance test. RESULTS: The mean number of radiographs per patient was 6. The
      linear test was significant in 46 patients. Two main types exist. Type A is an
      adolescent scoliosis that continues to progress after skeletal maturity, whereas
      type B appears or progresses late. There were 13 type A and 20 type B of which 11
      progressed around menopause. Significant differences were noted between groups A
      and B regarding loss of body height (group A, 5 cm and group B, 9.5 cm; P <
      0.001), rate of progression in lumbar single and thoracolumbar single curves
      (group A, 0.82 degrees/y and group B, 1.64 degrees/y; P < 0.004), Cobb first
      radiograph (group A, 37 degrees and group B, 20 degrees; P < 0.0001), age
      rotatory subluxation (group A, 42 years and group B, 56 years; P < 0.0001), and
      Cobb rotatory subluxation (group A, 52 degrees and group B, 29 degrees; P <
      0.0001). CONCLUSIONS: The originality of our study is the diagram. We
      demonstrated that the rate of progression was linear, and it can be used to
      establish an individual prognosis. The diagrams visualized 2 main distinct types.
      There was a significantly faster rate of progression in type B. In type A, rotary
      subluxation occurs during progression of the curvature. In type B, it seems to be
      the initial event. Menopause is a period of deterioration in type B.

PMID- 17495782
TI  - Erector spinae muscle changes on magnetic resonance imaging following lumbar
      surgery through a posterior approach.
AB  - STUDY DESIGN: Prospective randomized study of patients undergoing lumbar
      arthrodesis. OBJECTIVES: To quantify MRI changes of the erector spinae following
      lumbar surgery through a posterior approach and the possible protection of these
      muscles during surgery by the use of cholinergic blockade. SUMMARY OF BACKGROUND
      DATA: It has been shown that lumbar spine surgery through a posterior approach
      can induce iatrogenic lesions in the erector spinae. We have shown in a previous
      study that histologic changes on muscular biopsy performed in the multifidus at
      the end of the surgical procedure were not modified by the use of cholinergic
      blockade during surgery. METHODS: Twenty patients scheduled to undergo pedicle
      screw enhanced L4-L5 arthrodesis were enrolled in this study. Ten patients
      received curare during anesthesia and 10 patients did not. MRI was obtained the
      day before the operation and at 6 months of follow-up on the same MR scanner. T1
      weighted images were obtained in the axial plane. The 2 slices immediately
      proximal and distal to the pedicle screw construct on the postoperative MRI were
      selected. The corresponding slices were selected on the preoperative MRI. Each
      erector spinae on the 4 slices was surrounded using a mouse-guided tool. The
      contractile component of the cross-sectional area (CCSA) was calculated from the
      number of pixels surrounded and the signal intensity of each pixel. RESULTS:
      There was only slight changes in the erector spinae CCSA proximal to a posterior
      lumbar arthrodesis. Erector spinae CCSA decreased by 27% distal to the
      arthrodesis. Curare showed no efficacy in preventing muscle damage. CONCLUSIONS:
      Erector spinae muscle alterations mainly occur distal to posterior lumbar
      surgical procedures.

PMID- 17495783
TI  - Three-dimensional lumbar spine postures measured by magnetic resonance imaging
      reconstruction.
AB  - STUDY DESIGN: Investigation of method. OBJECTIVE: This study presents a novel
      method of accurately determining relative bone position in vivo using magnetic
      resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: Biomechanical modeling of
      the human body requires measurement of the relative positions of skeletal
      elements. Spinal orientation is particularly difficult to measure due to small
      joint movements, relative inaccessibility of the bones to direct measurement, and
      joint complexity. METHODS: A process incorporating both positional and
      conventional MRI was used to measure the skeletal positions of the lumbar spine
      and pelvis. The method uses higher quality conventional MRI to determine bone
      geometries and then registers these with lower resolution, positional MRI images
      of various postures to determine the relative locations of the bones.
      Flexion/extension, lateral bend, and axial twist rotations were measured for each
      joint. RESULTS: The results indicate good intrameasurer reliability, with a
      maximum rotational difference for all vertebral registrations of less than 1
      degrees and a maximum translational difference of less than 3 mm. While there did
      not appear to be significant patterns between the 2 Subjects, there were trends
      within each Subject as well as identifiable postural characteristics.
      CONCLUSIONS: Although processing times are currently lengthy, the data collected
      are 3-dimensional, and represent the anatomy and movement of a specific
      individual.

PMID- 17495785
TI  - Clinical research in burns: state of the science, 2006.

PMID- 17495784
TI  - Cervical transforaminal epidural steroid injections: more dangerous than we
      think?
AB  - STUDY DESIGN: Survey/case series. OBJECTIVE: To survey pain physicians about
      neurologic infarctions following cervical transforaminal epidural steroid
      injections (TF-ESIs). SUMMARY OF BACKGROUND DATA: Cervical TF-ESIs are commonly
      performed in patients with cervical radiculopathy, although there are no
      randomized controlled studies supporting their efficacy. Eight case reports of
      brain and spinal cord infarction have been published. In addition, one of the
      investigators (M.S.W.) has reviewed 4 cases of major cerebellum/brainstem
      infarction following cervical TF-ESIs with methylprednisolone. METHODS: To better
      characterize these complications, anonymous surveys were sent to all U.S.
      physician members of the American Pain Society. Respondents were asked about
      awareness of complications, year of occurrence, practice setting and specialty of
      the treating physician, use of fluoroscopy/contrast/local
      anesthetic/corticosteroid, doses administered, and CT/MRI/autopsy findings.
      RESULTS: Overall response rate was 21.4% (287 of 1340). In all, 78 complications
      were reported, including 16 vertebrobasilar brain infarcts, 12 cervical spinal
      cord infarcts, and 2 combined brain/spinal cord infarcts. Brain infarcts
      invariably involved the cerebellum, brainstem, or posterior cerebral artery
      territory. Thirteen cases resulted in a fatal outcome: 5 with brain infarcts, 1
      with combined brain/spinal cord infarcts, 1 following high spinal anesthesia, 1
      associated with a seizure, and 5 with unspecified etiology. All 4 cases with
      corticosteroid alone involved methylprednisolone, resulting in 3 cerebellar
      infarcts and 1 posterior cerebral territory infarct. Of these, 3 had fatal
      outcomes and 2 autopsies revealed no vertebral artery trauma. CONCLUSIONS: This
      study demonstrates a significant risk of serious neurologic injury after cervical
      TF-ESIs. A growing body of evidence supports an embolic mechanism, whereby
      inadvertent intra-arterial injection of particulate corticosteroid causes a
      distal infarct. Embolism to the distal basilar artery region can cause midbrain,
      pons, cerebellum, thalamus, temporal and occipital lobe infarctions. Other
      potential mechanisms of infarction include vertebral artery perforation causing
      dissection/thrombosis and needle-induced vasospasm.

PMID- 17495786
TI  - Lip incompetence and psychosocial effects: a pilot study.
AB  - OBJECTIVE: The purpose of the study was to determine whether children are more
      negatively perceived because of a lip incompetence. STUDY DESIGN: A sample survey
      study. METHODS: Two sets of colored pictures (1 set with the mouth open and 1 set
      with the mouth closed) were taken of four children with lip incompetence and
      mouth breathing and four children with normal lip closure and breathing patterns.
      These pictures were presented to a group of judges in Belgium and Brazil. Judges
      were presented either pictures of the closed mouth sets or pictures of the open
      mouth sets and were asked to rate on a 10-point scale the chance that the child
      was shy, had few friends, belonged to a lower socioeconomic class, had problems
      with reading, writing, or arithmetic, had ever manifested thumb-sucking, and had
      difficulties breathing through the nose. In each child, scores obtained for the
      open mouth set were compared with those obtained for the closed mouth set.
      RESULTS: There was no consistent pattern of higher scores being assigned to the
      pictures of the open mouth set, neither in the Belgian survey nor in the
      Brazilian survey. CONCLUSION: Contrary with past and present claims, results
      suggest that children with a lip incompetence are not necessarily perceived
      negatively.

PMID- 17495790
TI  - Progress in hepatitis B prevention through universal infant vaccination--China,
      1997-2006.
AB  - Hepatitis B virus (HBV) infection is a leading cause of illness and death in
      China. Approximately 60% of the population has a history of HBV infection, and
      9.8% of persons in China are chronically infected with HBV and at risk for
      premature death from liver disease. Each year, an estimated 263,000 persons in
      China die from HBV-related liver cancer or cirrhosis, accounting for 37%-50% of
      HBV-related deaths worldwide. Because most HBV infections occur during infancy or
      early childhood, when HBV infection is most likely to become chronic, vaccination
      of infants beginning at birth is the key strategy for preventing chronic HBV
      infection. This report describes China's progress in increasing coverage among
      infants with hepatitis B vaccine (HepB) and timely administration of the HepB
      birth dose (i.e., within 24 hours of birth). Infant vaccination coverage with
      both the timely birth dose and the complete vaccine series was substantially
      higher among children born during 2003 than among those born during 1997; timely
      birth-dose coverage increased from 29.1% to 75.8%, and HepB series completion
      increased from 70.7% to 89.8%. Furthermore, in economically disadvantaged
      populations in western and middle provinces targeted by the China-Global Alliance
      for Vaccines and Immunization (China-GAVI) project, reported coverage with timely
      HepB birth dose increased from 64% in 2004 to 81% in 2006, and coverage with the
      complete HepB series increased from 52% in 2001 to 92% in 2006. China has
      established a goal to reduce chronic HBV infection among children aged <5 years
      to <1% by 2010. Achieving this goal will require continued commitment to
      increasing vaccination coverage in impoverished regions and ensuring that infants
      born at home are vaccinated within 24 hours of birth.

PMID- 17495791
TI  - Characteristics of persons with chronic hepatitis B--San Francisco, California,
      2006.
AB  - Chronic hepatitis B is the most common cause of cirrhosis and liver cancer
      worldwide. Approximately 45% of the world's population lives in regions where
      chronic hepatitis B virus (HBV) infection is endemic, including most of Asia and
      the Pacific Islands, Africa, and the Middle East. Nearly one fourth of the
      population of San Francisco was born in Asia and the Pacific Islands. In 2006,
      the San Francisco Department of Public Health (SFDPH) received reports consistent
      with probable chronic HBV infection for 2,238 persons. To characterize persons
      with reported confirmed chronic HBV infection in San Francisco in 2006, SFDPH
      collected additional data on a subset of 567 cases reported to the SFDPH chronic
      hepatitis B registry. Eighty-four percent of the persons were Asians/Pacific
      Islanders (A/PIs), 80% of whom were foreign born. Fewer than half had been
      referred to a gastroenterologist/hepatologist for evaluation at the time of
      reporting. Persons with chronic HBV infection can benefit from medical care by
      providers with expertise in viral hepatitis. In addition, close contacts of
      infected persons should be screened and offered vaccination if found to be
      susceptible to HBV infection. Culturally appropriate counseling for and follow-up
      of persons with chronic HBV infection and their contacts could help reduce the
      transmission of HBV infection.

PMID- 17495792
TI  - CDC's 60th anniversary: director's perspective--William L. Roper, M.D., M.P.H.,
      1990-1993.
AB  - The years 1990-1993 saw tremendous change in public health. CDC expanded its
      effectiveness and capacity by building key partnerships with academia, public
      health agencies, and the private sector. The explosion of telecommunications
      greatly enhanced CDC's ability to communicate the results of studies and
      recommendations directly with the public, which increased the visibility of the
      agency and the public health community. The agency's priorities were clear:
      strengthening the public health infrastructure, improving the health of children,
      and making prevention a practical reality in the nation's health system.

PMID- 17495793
TI  - Surveillance of certain health behaviors among states and selected local areas-
      United States, 2005.
AB  - PROBLEM: Behavioral risk factors such as smoking, poor diet, physical inactivity,
      and excessive drinking are linked to the leading causes of death in the United
      States. Controlling these behavioral risk factors and using preventive health
      services (e.g., influenza and pneumococcal vaccination of adults aged > or =65
      years and hypertension and cholesterol screenings) can substantially reduce the
      morbidity and mortality in the U.S. population. Continuous monitoring of these
      behaviors and preventive services are essential for developing health promotion,
      intervention programs, and health policies at the state, city, and county level.
      REPORTING PERIOD COVERED: Data collected in 2005 are presented for
      states/territories, selected metropolitan and micropolitan statistical areas
      (MMSAs), metropolitan divisions, and selected counties. DESCRIPTION OF THE
      SYSTEM: The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing,
      state-based, random-digit--dialed telephone survey of the noninstitutionalized
      U.S. population aged > or =18 years. BRFSS collects information on health risk
      behaviors and preventive health services related to leading causes of death. All
      50 states, the District of Columbia (DC), the Commonwealth of Puerto Rico, and
      the U.S. Virgin Islands participated in BRFSS during 2005. Within these states
      and territories, 153 MMSAs and 232 counties that reported data for at least 500
      respondents or a minimum sample size of 19 per weighting class were included in
      the analyses. RESULTS: Prevalence of health-risk behaviors, awareness of specific
      medical conditions, and use of preventive services varied substantially by
      state/territory, MMSA, and county. In 2005, prevalence of health insurance ranged
      from 60% to 95% for states/territories, MMSAs, and counties. Prevalence of
      leisure-time physical inactivity ranged from 16% to 49% for states/territories,
      14% to 36% for MMSAs, and 12% to 41% for counties. Prevalence of adults who
      engaged in at least moderate physical activity ranged from 33% to 62%, and
      prevalence of vigorous physical activity ranged from 15% to 42% for
      states/territories, MMSAs, and counties. Prevalence of adults who currently smoke
      cigarettes ranged from 6% to 35% for states/territories, MMSAs, and counties. The
      prevalence of binge drinking was substantially higher than the prevalence of
      heavy drinking across all the states/territories, MMSAs, and counties. Prevalence
      of adults who were overweight ranged from 53% to 67 % for states/territories, 49%
      to 70% for MMSAs, and 44% to 71% for counties. Prevalence of current asthma
      ranged from 4% to 14% for states/territories, MMSAs, and counties. Prevalence of
      diabetes ranged from 4% to 14% for states/territories and MMSAs and from 3% to
      14% for counties. Proportion of respondents with high blood pressure ranged from
      13% to 39% for states/territories, MMSAs and counties. Prevalence of respondents
      with high cholesterol ranged from 31% to 41% for states/territories and 26% to
      47% for MMSAs and counties. The prevalence estimates for respondents who reported
      being limited in any way in any activities because of physical, mental, or
      emotional problems ranged from 10% to 27% for states/territories, 12% to 31% for
      MMSAs, and 10% to 27% for counties. The percentage of respondents who required
      use of special equipment ranged from 4% to 10% for the states/territories, 3% to
      15% for MMSAs, and 3% to 11% for counties. Prevalence of fair or poor health
      ranged from 11% to 34% for states/territories and 6% to 26% for MMSAs and
      counties. The prevalence of adults who checked their cholesterol during the
      preceding 5 years ranged from 55% to 86% for states/territories, MMSAs, and
      counties. Prevalence of annual influenza vaccination among adults aged > or =65
      years ranged from 32% to 78% for states/territories, 48% to 83% for MMSAs, and
      41% to 84% for counties. The estimated prevalence of pneumococcal vaccination
      among adults aged > or =65 years ranged from 28% to 72% for states/territories,
      52% to 82% for MMSAs, and 35% to 83% for counties. INTERPRETATION: The findings
      in this report indicate a wide variation in health-risk behaviors, chronic
      conditions, and use of preventive services among U.S. adults at the
      state/territory, MMSA, and county level. The findings underscore a need for
      continuous efforts to evaluate public health intervention programs and policies
      designed to reduce morbidity and mortality caused by chronic disease and injury.
      PUBLIC HEALTH ACTION: The 2005 BRFSS data indicate a need for continued
      monitoring of health-risk behaviors, specific disease conditions, and use of
      preventive services to identify high-risk populations and to implement and
      monitor health-promotion programs and health policies at the state/territory,
      MMSA, and county level.

PMID- 17495794
TI  - [Diagnosis and treatment of benign paroxysmal postural vertigo].
AB  - The article describes pathogenetic aspects, clinical picture, principal
      diagnostic methods and treatment of patients with benign paroxysmal postural
      vertigo (BPPV). The evidence obtained at examination of 148 patients with
      complaints for vertigo episodes is provided. The group of 29 patients with a
      positive Dix-Holpike test was analysed. BPPV onset correlated with age, gender,
      prevalence of the pathological process location on the right, presence of
      labyrinthine hydropse.

PMID- 17495795
TI  - [Laser destruction of labyrinthine receptors as a treatment for benign paroxysmal
      postural vertigo and otolith symptoms].
AB  - Outcomes of surgical laser treatment are presented for 15 patients with resistant
      to conservative therapy benign paroxysmal postural vertigo (BPPV) and otolith
      related disorders. Nine patients with Meniere's disease with BPPV (n=3) and
      otoliths (in all the patients) were exposed to laser impulses on the bony wall of
      the horizontal semicircular canal. The impulse was directed in the lumen of the
      canal in 6 patients with BPPV and otolith symptoms. In Meniere's patients vertigo
      stopped, hearing was at the preoperative level. Neither threy had BPPV nor
      otolith problems. The same results were obtained in 6 patients with the other
      diseases. Vestibular excitability of all surgically treated patients decreased to
      the fifth degree.

PMID- 17495796
TI  - [Acoustic dysfunction and microcirculation in patients with diabetes mellitus].
AB  - Modern electrophysiological methods (audiometry and biomicroscopy of the bulbar
      conjunctiva vessels) have been used in 157 patients with diabetes mellitus (DM)
      to study the acoustic function and microcirculation. Common vascular reactions of
      the eyeball and brain allow using the data of biomicroscopy of bulbar conjunctiva
      vessels for evaluation of cerebral hemodynamics in DM patients. DM causes hearing
      and microcirculatory disorders. A close correlation exists between duration of DM
      and disturbances in the acoustic analyzer (microcirculation). This should be
      considered in planning preventive and therapeutic measures in neurosensory
      hypoacusis in DM.

PMID- 17495797
TI  - [Clinical features of vocal disorders in population of megapolis].
AB  - Vocal problems in population of a megapolis are caused, primarily, by acute
      inflammation of the upper respiratory tract of viral etiology and exacerbation of
      chronic pharyngolaryngitis in smokers and vocal professionals. Organic diseases
      of the vocal folds are rare finding in outpatients (0.2-0.3%). Functional vocal
      disorders are accompanied by other diseases: hypertension, cervical
      osteochondrosis, hormonal abnormalities. Therefore, normalization of voice is
      impossible without treatment os such diseases. Functional voice disorders
      manifest with reduction of time of fonation expiration >17 seconds, by clavicular
      or thoracic-clavicular respiration, abdominal respiration, a decrease of vital
      capacity of the lungs, positive ventalin test, low voice sound intensity,
      constrained timbre.

PMID- 17495798
TI  - [Correlation between immunohistochemical indices of adenoid vegetations and
      health of ailing children].
AB  - We studied correlations between clinical characteristics of ailing children and
      their immunohistochemical parameters. Clinical status was assessed by the degree
      of adenoid vegetations, duration of the disease, the presence of chronic
      tonsillitis or its combination with adenoiditis. We used the following
      immunohistochemical parameters: the level of CD3+ in histological slices and the
      presence or absence of IgA-producing cells. Correlation was found between the
      presence or absence of IgA-producing cells and the degree of adenoid vegetations
      as well as the presence only of chronic tonsillitis or chronic tonsillitis plus
      adenoiditis. We found also important but statistically insignificant differences:
      in a group of patients with the disease duration up to 2 years CD3+ cells were
      absent, while in children with the disease duration more than 5 years these cells
      were present. Thus, immunohistochemical parameters are rather informative in
      interpretation of a clinical picture in ailing children.

PMID- 17495799
TI  - [Prevention of stable hypoacusis in patients with acute otitis media].
AB  - We studied 788 patients with acute otitis media caused by cooling, common cold
      and made an experiment with cooling guinea pigs and white rats that developed
      noninvasive acute otitis media (AOM). We registered morphological and
      histochemical changes in the hearing organ at different stages of AOM. We
      discovered that neurosensory hypoacusis in AOM results from disturbed
      microcirculation in the ear leading to hypoxia and affection of metabolic
      processes in the receptors of the hearing system. We propose a scheme of combined
      therapy at different stages of AOM. We believe that rehabilitation of the hearing
      system should be started as early as the initial symptoms of acute inflammation
      of the middle ear and continued to a complete recovery of the acoustic function.

PMID- 17495800
TI  - [Modification of indirect optic videolaryngoscopy in diagnosis of laryngeal
      pathology in infants].
AB  - Laryngeal examination of infants with rigid optic instruments is described.
      Clinical cases are reported.

PMID- 17495801
TI  - [Alloplasty of laryngotracheostoma with polypropylene net Esfil].
AB  - Application of artificial materials in laryngotracheoplasty is reviewed. The
      experience in implantation of a net prosthesis Esfil made of polypropylene
      monofilament for repair of laryngo- and tracheostomas in 7 patients is described.
      A positive long-term outcome of alloplasty occurred in 6 cases. Factors promoting
      uncomplicated incorporation of the prosthesis are outlined.

PMID- 17495802
TI  - [Therapeutic and diagnostic policy in nasal bleeding in patients with acute
      leukemia].
AB  - The algorithm of the otorhinolaryngologist's actions in nasal bleeding (NB) in
      acute leukemia (AL) patients is presented. Some aspects of NB pathogenesis in AL
      are considered. A working classification and an original technique of nasal
      tamponade using the drug tahocomb in AL patients with nasal bleeding are
      proposed.

PMID- 17495803
TI  - [Variants of plastic operations on the anterior wall of the frontal sinus].
AB  - Variants of plastic reconstruction of the frontal sinus anterior wall in its
      traumatic lesion is reviewed. Examination and treatment of 17 patients with the
      diagnosis of fracture of the frontal sinus anterior wall with a cosmetic defect
      were performed in Moscow hospital N 1. Plastic reconstruction consisted of
      reposition of the bone fragments with elevator (6 patients), reposition and
      suturing of the fragments to the border of the bone defect (9 patients). Follow
      up proved efficacy of the above surgical treatment in repair of the cosmetic
      defect. Architectonics of the walls of the frontal sinus was restored,
      pyoinflammation in the sinus was absent, passability of the frontonasal
      anastomosis was unaffected.

PMID- 17495804
TI  - [Parodontal tissues reaction to filling of dental root defect with different
      materials in experiment].
AB  - In experimental study on 4 mongrel 4-5 year old dogs under intravenous anesthesia
      (rometar) after turning back of mucous-periosteum flap and forming artificial
      defects of hard tissues in the upper third of a dental root the defects were
      filled with glass-ionomer cement (Ketac-molar, 3M-Espe), composite light cured
      material (Heliomolar flow, Ivoclar-Vivadent), amalgam with high silver content
      (Amalcap Plus regular non-Gamma-2, Ivoclar-Vivadent) or with material for dental
      root perforation closure (PRO-Poot mta, Dentsply). It was found that parodontium
      reacted to these filling materials by inflammation. The glass-ionomer cement and
      material for dental root perforation closure had lesser effect on parodontium in
      comparison with composite and amalgam.

PMID- 17495805
TI  - [Parodontal tissues microcirculatory status of the abutment teeth in cases of
      restricted dentition defect prosthetic treatment].
AB  - The study of the parodontal tissues microcirculatory status of the abutment teeth
      in restricted dentition defect has established that microvessel reaction in
      gingival tissues at the stage of supporting teeth preparation was accompanied by
      development of congestion development in microcirculatory bed that was relieved
      in 2 weeks in intact parodontium and in case of its inflammation--increased even
      greater. Functional loading of supporting teeth in case of restricted dentition
      defect prosthetic treatment with bridge constructions led to congestive hyperemia
      in gingival microcirculatory bed that was relieved in 1-3 months depending upon
      the parodontium status.

PMID- 17495806
TI  - [Immediate implantation and the role of early functional loading of the implant].
AB  - Experimental morphologic study was performed on lab mini-pigs (biological model)
      to determine optimal time for functional loading in intraosseous implantation (1,
      3, 6.5 months). Morphologically, connective tissue capsule developed around the
      implant within 1 to 6.5 months. It quickly matured, condensed and thinned due to
      reparative osteogenesis. It was also observed that the bone mass grew on the
      implant surface and alveolar process changed equivalent to functional loads.
      Prevalence of connective tissue or supporting structures in implant/bone tissue
      zone depended mainly upon anatomical-topographical conditions in the oral cavity
      and achievement of primary stabilization.

PMID- 17495807
TI  - [Study of different adhesive systems adhesion to dentine].
AB  - The breaking strength of different adhesive systems (AdheSE, Contax, Ecusit
      Primer Mono and Clearfil Se Bond) was studied on 60 teeth. The most breaking
      strength was demonstrated by system Clearfil Se Bond--29.434+/-0.350 MPa. The
      least breaking strength from the studied bondings was demonstrated by the system
      AdheSe--23.708+/-0.068 MPa. The breaking strength of the adhesive system Clearfil
      Se Bond was by 21% higher than the corresponding value of the system Contax
      (24.312+/-0.086 MPa) and by 11% higher than the corresponding value of the system
      Ecusit (26.504+/-0.143 MPa).

PMID- 17495808
TI  - [Comparative study of immunocompetent cells of dental pulp of intact teeth, teeth
      with carious lesion and its complications combined with parodontitis].
AB  - Results of the comparative immunohistochemical study of dental pulp by means of
      monoclonal antibodies to CD3, CD20, capital ES, CD68 are described. Pulp from the
      patients with caries, acute and chronic pulpitis in combination with
      periodontitis on different stages was studied, the qualitative and quantitative
      feature of dental pulp immune cells--T- and B-lymphocytes and macrophages was
      determined.

PMID- 17495809
TI  - [Clinical laboratory substantiation of immunocorrection use in comprehensive
      treatment of chronic catarrhal gingivitis].
AB  - The role of immune system in development of chronic catarrhal gingivitis in 60
      primary patients was defined and substantition of immunocorrection with Licopid
      in combined treatment was done.

PMID- 17495810
TI  - [Evaluation of efficacy of demineralized bone transplant use in surgical
      treatment of patients with periapical inflammatory-destructive processes in the
      jaws].
AB  - The aim of the study was to raise the efficacy of surgical treatment of patients
      with periapical inflammatory-destructive processes in the jaws in chronic and
      exacerbation stages. It was established that the use of demineralized bone
      transplant as osteoplastic material intensified bone tissue reparative
      regeneration, promoted complete bone regenerate recovery in the region of remote
      destruction foci earlier than preparations based on calcium hydroxyapatite.

PMID- 17495811
TI  - [Diagnosis of temporo-mandibular joint dysfunction caused by occlusion pathology
      and treatment of such patients].
AB  - Patients with temporo-mandibular joint (TMJ) dysfunction need complex treatment
      that includes prosthetic treatment in intrajoint relation stabilization. In cases
      of TMJ pathology it is necessary to examine patients and make axiography,
      function analysis, MPI-analysis, magnetic resonance tomography and zonography of
      TMJ, electromyography of the masticatory muscles. The authors examined 47
      patients with TMJ dysfunction, 43 of them had occlusion pathology. We managed to
      eliminate the dysfunction symptoms and to receive stable result of the treatment
      in all the patients.

PMID- 17495812
TI  - [Study of static strength of screw connection of intra- and extraosseous parts of
      the implants LIKo].
AB  - An examination was done in an attempt to reveal the connection between
      configuration of a nexus and the inner and outer-ortho (bone-constituted) parts
      (supra-structures) of the bi-leveled dental implants at a point of connectivity
      of the entire system. The ensuing recommendation (in accordance with the
      examination) focuses on the analysis of the strength of the fixation of the
      implants' screws with the aim of excluding a possibility of micro-mobility at the
      connection point of the entire system. The result of the examination yielded the
      principles of resistance against the lateral pressure, dependent upon the shape
      of the supra-structures.

PMID- 17495813
TI  - [A new method of complex diagnosis and treatment of temporo-mandibular joint
      dysfunction].
AB  - Three cases of a new method of complex diagnosis and treatment of temporo
      mandibular joint dysfunction using individual jaws articulator designed and
      patented by the author are reported.

PMID- 17495814
TI  - [Two-layer adhesive film Diplen-denta C--a new compound containing polymer base
      and active component Solcoseryl].
AB  - Characteristics of the main components of a new effective long-lasting dosage
      form--biopolymer two-layer adhesive solcoseryl containing film Diplen-denta C-
      are presented. It has a potent wound-healing action on oral mucosa, retains
      therapeutic properties during long time, is self dissolving and can be easily
      fixed on oral mucous membrane.

PMID- 17495815
TI  - [Effect of therapy with atorvastatin on parameters of postprandial lipemia and
      factors of inflammation in patients with ischemic heart disease].
AB  - Reaction of parameters of lipid transport system to standard fat load (J.Patsch
      method), C-reactive protein (CRP) and fibrinogen levels were studied in 30
      patients with ischemic heart disease before and after 3 months of therapy with
      atorvastatin (10 mg/day). Atorvastatin therapy resulted in 25, 34, 17 and 16%
      lowering of concentrations of total cholesterol (CH), low density lipoprotein CH,
      triglycerides (TG), and apolipoprotein (apo) B, respectively, 6 and 9% elevation
      of high density lipoprotein CH and apo A-1 levels, respectively. Moreover
      atorvastatin improved although not completely normalized parameters of
      postprandial lipemia: significant lowering of baseline (-17%), 3 (-19%) and 6
      hour (-14%) post load TG levels was noted. However relative TG elevation from
      baseline level to 3 and 6 hours after fat load did not change (+100 and 148%
      before, +95 and 156% after treatment, respectively). Changes of CRP (-22%) and
      fibrinogen (-8%) were not significant (p>0.05).

PMID- 17495816
TI  - [Insulin-glucose parameters in healthy women and patients with arterial
      hypertension and ischemic heart disease in dependence on age and follicle
      stimulating hormone levels].
AB  - Insulin-glucose parameters in healthy women do not significantly change with
      changes of functional state of ovaries. Women with hypertension and normal levels
      of glycemia have significantly higher values of basal insulinemia and HOMA-R
      index reflecting presence of moderate insulin resistance degree of which is more
      pronounced in middle aged patients. In women with documented ischemic heart
      disease values of basal insulinemia, HOMA-R index, and glycemia are comparable
      with those in patients with hypertension and follicle-stimulating hormone level
      above 30 IE/l and significantly differ from corresponding parameters in healthy
      women in peri- and postmenopause.

PMID- 17495817
TI  - [Immediate results of endovascular treatment of coronary arteries in patients
      with ischemic heart disease].
AB  - AIM: To assess immediate results of percutaneous coronary interventions (PCI) and
      finding the predictors of the successful outcomes in various subgroups of
      patients with coronary artery disease (CAD). MATERIAL: Patients (n=1066, (average
      age 55.7+/-9.2 years, women 12%) treated with coronary artery stenting between
      1999 and 2004. According to coronary angiography, 383 (36%) patients had 1
      vessel, 502 (47%) - 2-vessel, and 181 (17%) - 3-vessel CAD. The endovascular
      treatment was made on 1694 coronary stenoses (in average 1.6 stenosis/patient),
      356 stenoses (21%) was defined as type A, 745 (44%) - type capital B, and 593
      (35%) - type C. PCI was performed with use of inhibitors of glycoprotein
      receptors IIb/IIIa in 107 (18%) patients. RESULTS: The complete or partial
      immediate procedural success of PCI (elimination of at least one coronary
      stenosis) was achieved in 1002 (94%) patients. The immediate success was achieved
      in 1575 stenoses (93%). Total rate of major adverse cardiac events (MACE) was
      1.3%. There were no deaths, 11 patients (1%) had acute myocardial infarctions, 3
      (0.28%) patients had an emergent coronary artery bypass grafting. The immediate
      procedural success was significantly lower in patients with chronic coronary
      occlusions (76%) than in patients without coronary occlusions (97%, p<0.0001), as
      well in patients with stenoses type C as compared with stenoses type A, and B
      (success rate 77%, 98% and 100%, accordingly, p<0.0001). CONCLUSION: By
      multifactorial analysis, independent predictors of procedural failure were
      stenosis type C (small p<0.0001) and chronic occlusion of coronary artery
      (p=0,03).

PMID- 17495818
TI  - [Derangements of contractility of left ventricular myocardium in patients
      subjected to coronary bypass surgery. Methods of their correction].
AB  - Coronary bypass grafting with the use of cardiopulmonary bypass was performed in
      119 patients (age 41-75 years) with stable angina. In addition to standard
      therapy in pre and post operative periods patients of group 1 (n=40) received
      mildronate (750 mg/day for 3 days then 750 mg twice weekly), patients of group 2
      (n=41) received trimetazidine (70 mg/day). Patients of group 3 (n=38) received no
      "metabolic" drugs. The use of cardioprotectors mildronate and trimetazidine
      facilitated improvement of total and local myocardial contractility both before
      and after surgery, and caused limitation of development of myocardial stunning,
      associated with derangement of local contractility in post operative period.

PMID- 17495819
TI  - [Randomized FARVATER study. Part 2. Effect of atorvastatin on endothelial
      function, distensibility and stiffness of vascular wall].
AB  - AIM: To elucidate effect of two doses of atorvastatin (10 and 20 mg/day) on
      endothelial function, distensibility and stiffness of vascular wall. MATERIAL AND
      METHODS: Patients (n=50) with documented ischemic heart disease and
      hyperlipidemia were randomized to 10 or 20 mg/day of atorvastatin (Atoris, KRKA).
      Endothelial function and common carotid artery wall distensibility and stiffness
      were assessed at baseline and after 12 and 24 weeks of treatment. RESULTS:
      Administration of both 10 and 20 mg/day doses of atorvastatin for 6 weeks was
      associated with significant lowering of total cholesterol (CH), triglycerides
      (TG) and low density lipoprotein (LDL) CH (24.5, 18.4, 34.9% and 29.1, 28.2,
      40.9%, respectively). After 24 weeks LDL CH lowering from baseline reached 34.9
      and 43.9% (p<0.001) and that of TG - 22 and 15%, in 10 and 20 mg/day groups,
      respectively. There were no significant differences between 10 and 20 mg/day
      groups in baseline values of endothelium dependent vasodilation (EDV), carotid
      artery distensibility and stiffness (7.28 and 6.64%, 21.60 and 20.15, 8.04 and
      9.19 U, in 10 and 20 mg/day groups, respectively). After 3 months of treatment
      there occurred significant 38.4% (10 mg/day) and 45.4% (20 mg/day) increases of
      EDV. Significant 27.6% (10 mg/day) and 28.8% (20 mg/day) enhancement of vascular
      distensibility was noted after 24 weeks. Vascular wall stiffness decreased 33.4%
      (p=0.008) and 31.3% (p=0.002) in 10 and 20 mg/day groups, respectively.

PMID- 17495820
TI  - [Effect of cardiac resynchronization therapy on quality of life of patients with
      chronic heart failure].
AB  - AIM: To study quality of life of heart failure patients who underwent cardiac
      resynchronization therapy. MATERIAL AND METHODS: Cardiac resynchronization
      devices were implanted to 27 consecutive patients (69.7+/-11.9 years of age) with
      severe heart failure (NYHA class III-IV). Follow up period was 11.6+/-4.9 months.
      Changes of parameters of quality of life (measured by questionnaire SF-36), ECHO
      characteristics (left ventricular ejection fraction, end-diastolic diameter, end
      systolic diameter, pulmonary artery blood pressure, mitral and tricuspid
      regurgitation), six-minute walk distance were assessed at baseline and in 2, 6,
      and 12 months after implantation of resynchronization device. RESULTS: Cardiac
      resynchronization therapy improved quality of life according to physical and
      emotional scales. Changes of the following hemodynamic characteristics were
      positive: ejection fraction (from 30.6+/-4,2% at baseline to 43.4+/-5.1, 46.8+/
      0.3, 45.7+/-3.4% in 2, 6, 12 months after implantation, respectively), end
      diastolic diameter (from 82+/-2 mm at baseline to 76+/-3, 73+/-2, 75+/-4 mm in 2,
      6, 12 months after implantation, respectively), end-systolic diameter (from 56+/
      2 mm at baseline to 53+/-2, 51+/-1, 52+/-3 mm in 2, 6, 12 months after
      implantation, respectively), pulmonary artery blood pressure (from 44+/-4 mm Hg
      at baseline to 35+/-3, 30+/-5, 34+/-4 mm Hg in 2, 6, 12 months after
      implantation, respectively), mitral regurgitation degree (from 2.8+/-0.2 at
      baseline to 2.4+/-0.2, 2.3+/-0.1, 2.5+/-0.3 in 2, 6, 12 months after
      implantation, respectively) and tricuspid regurgitation degree (from 2.5+/-0.1 at
      baseline to 2.1+/-0.2, 2.1+/-0.1, 2.2+/-0.2 in 2, 6, 12 months after
      implantation, respectively). Moreover, six minutes walk distance significantly
      improved (from 212+/-18 m at baseline to 270+/-14, 286+/-17 and 278+/-13 m in 2,
      6, and 12 months after cardiac resynchronization device implantation,
      respectively). CONCLUSION: Cardiac resynchronization therapy improves quality of
      life of patients with terminal stage heart failure.

PMID- 17495821
TI  - [Pulmonary hypertension and right ventricular failure. Part VII. Epidemiology,
      risk factors, and pathogenesis of primary (idiopathic) pulmonary arterial
      hypertension].
AB  - In a series of articles the authors discuss literature data concerning
      epidemiology of pulmonary arterial hypertension (PAH), its modern classification;
      peculiarities of its pathogenesis and analysis of results of epidemiological and
      cohort studies. Rate of new cases of PAH is 1-2, prevalence - approximately 15
      cases per million of adult population. This part contains detailed discussion of
      definite, probable and possible risk factors of PAH which comprise some drugs
      (anorexigens, amphetamines, meta- amphetamines), HIV infection, collagen vascular
      diseases, congenital systemic-to-pulmonary shunts, portal hypertension, and some
      hematological diseases. Analysis of literature data concerning interaction of
      genetic predisposition and factors of internal and external environment in
      pathogenesis of PAH as well as presentation of direct and indirect proofs of key
      role of serotonin in pathogenesis of PAH of various genesis are also included.

PMID- 17495822
TI  - [ Psychological stress and acknowledgement of its value as a first order
      cardiovascular risk factor].
AB  - The paper contains analysis of results of recent studies of relationships between
      stress and cardiovascular morbidity and mortality. A variety of stress reactions
      are depicted: acute stress, chronic stress, as well as models of work stress.
      Pathophysiologic mechanisms of links between stress and cardiovascular morbidity
      and mortality are discussed, and most effective methods of correction of elevated
      levels of stress and their clinical and prognostic value for treatment of
      ischemic heart disease are presented.

PMID- 17495823
TI  - [Thoracoscopy in the treatment of intrapleural bleeding due to injury of chest
      wall vessels].
AB  - Thoracoscopy was used in the treatment of 141 patients with penetrating wounds of
      chest. Injuries of chest wall vessels were diagnosed at 68 (48.2%) patients. Rate
      of thoracoscopy conversion due to bleeding from chest wall wounds was 4.3%.
      Thoracoscopy is effective at injuries of intercostals arteries and their muscular
      branches, but injuries of internal thoracic artery require conversion into
      thoracotomy at 50% cases. It is revealed that expediency of thoracoscopy is in
      direct proportion to time from injury point and is inversely to hemothorax
      volume.

PMID- 17495824
TI  - [Clinical and special diagnosis of aneurysms of descending and thoracoabdominal
      aorta].
AB  - Clinical and special diagnosis of aneurysms of descending and thoracoabdominal
      aorta is discussed. Polymorphism and non-specificity of clinical symptoms
      (clinical masks to 31.9%), asymptomatic forms (to 55.5%) demand special
      diagnostic methods for right diagnosis and choice of surgery type.

PMID- 17495825
TI  - [Surgical procedures on aorto-iliac segment from mini-approach in chronic lower
      limb ischemia].
AB  - First experience of reconstructive surgeries on aorto-iliac segment from mini
      approach at 62 patients (1st group) is analyzed. Control (2nd) group consisted of
      80 patients operated with traditional techniques. Both groups were similar by
      main parameters; patients of 1st groups had more concomitant diseases. Mini
      invasive methods did not lead to increase of overall surgery and aorta clamping
      time. Postoperative period was easier at patients of 1st group. Postoperative
      complications were seen at 5 (8%) patients of 1st group, 1 (1.6%) patient died;
      at 2nd group the postoperative complications were diagnosed at 8 (10%) patients,
      2 (2.5%) patients died. The postoperative hospital stay was 8.47+/-0.9 days at
      patients of 1st group compared with 15.7+/-1 days at patients of 2nd group.

PMID- 17495826
TI  - [Comparative results of standard and mini-invasive approaches at aorto-bifemoral
      grafting].
AB  - Technical features and results of aorto-bifemoral grafting from complete median
      laparotomy (20 patients) and median mini-laparotomy (20 patients) were compared
      in randomized study. Time of operation, stay in postoperative room,
      intraoperative bloodless, time of rehabilitation were less in mini-laparotomy
      group. Technical results at both groups were identical. General efficacy
      evaluated as sum of tested parameters (including subjective scale of health
      state) was also statistically higher at this group.

PMID- 17495827
TI  - [Surgical aspects of the treatment of generalized peritonitis].
AB  - Advantages and disadvantages of different methods of surgery termination at
      generalized peritonitis are discussed. Drainage of abdominal cavity can not
      guarantee adequate sanation. Disadvantages of peritoneal lavage exceed the
      clinical value of this method. Active influence on infectious process during
      postoperative period can be realized with laparostomy, programmed revisions and
      sanations of abdominal cavity. These methods lead to recovery of more 80%
      patients with generalized peritonitis. Laparoscopic sanation is effective when
      bacterial contamination of peritoneal exudation doesn't exceed 10(5) mb/g.

PMID- 17495828
TI  - [New technologies in the treatment of gastroesophageal reflux disease].
AB  - Surgical treatment of 298 patients with gastroesophageal reflux disease with both
      laparotomy and mini-invasive technologies is analyzed. New method of anti-reflux
      surgeries using synthetic implants is described. Short- and long-term results are
      analyzed. Advantage of laparoscopic procedures is demonstrated in long-term
      period. Excellent and good results were achieved at 82.3% patients.

PMID- 17495829
TI  - [Early diagnosis and surgical tactics at acute destructive pancreatitis].
AB  - Based on retrospective analysis of 292 case histories of patients with acute
      pancreatitis the computed model permitted to differentiate destructive and
      hydropic pancreatitis and to predict clinical course of pancreonecrosis has been
      constructed. Algorithm of treatment tactics depending on this analysis has been
      developed. Use of laparoscopy in early period with results of computed prognosis
      permitted to decrease the rate of diagnostic mistakes at pancreonecrosis from
      59.2 to 39.5%. Algorithm of surgical tactics permitted to reduce lethality at
      small- and medium-focal pancreonecrosis from 51.7 to 5.1%, and the rate of
      purulent complication--from 23.8 to 2.5%.

PMID- 17495830
TI  - [Blood-preserving technologies at abdominal surgery].
AB  - Results of treatment of 112 patients with surgical diseases of abdominal cavity
      are analyzed. Blood-preserving technologies were used at 52 of them; the others
      were treated with traditional allohemotransfusion. It was demonstrated that
      ozonation of auto-blood before reinfusion permitted to exfuse the great volume of
      blood without negative effects. Ozone therapy during and after operation promoted
      decrease of postoperative complications and overall number of antibiotics and
      analgetics.

PMID- 17495831
TI  - [Regional intraarterial chemoimmunotherapy in complex treatment of patients with
      colon cancer complicated by metastatic lesion of the liver].
AB  - Results of combined treatment of 48 colon cancer patients with metastases to the
      liver are analyzed. Efficacy of regional intraarterial chemoimmunotherapy with
      recombinant interleukine-2 (ronkoleukine) is evaluated. The results of the
      treatment demonstrate that regional intraarterial chemoimmunotherapy with
      recombinant interleukine-2 is a safe and promising method in combined treatment
      of advanced colon cancer, increases survival and improves quality of life.

PMID- 17495832
TI  - [Prophylaxis of acute postoperative gastroduodenal ulcers at the patients with
      colorectal cancer].
AB  - Effective method for prophylaxis of acute postoperative gastric ulcers and
      erosions was developed. The core of this method is ozone therapy in preoperative
      period. Intensity of blood serum and erythrocytes chemiluminescence and ATPase
      activity of erythrocytes were studied at 86 patients with colorectal cancer
      before surgery and at 1st and 4th days of postoperative period. It was
      demonstrated that preoperative ozone therapy promoted normalization of free
      radical reactions and ATPase activity at postoperative period.

PMID- 17495833
TI  - [Laparoscopic-assisted method of surgical treatment of perforated gastric and
      duodenal ulcer].
AB  - Conversion (laparoscopic-assisted) method of surgical treatment of perforated
      gastric and duodenal ulcer was used at 103 patients. This method combines
      minilaparotomy with videolaparoscopy. Mean duration of surgery was 53 min, mean
      hospital stay - 6 bed-days. Postoperative complications were seen at one patient.
      There was no lethal outcome whereas lethality after open surgeries was 3.8%. It
      is concluded that mini-invasive methods of perforated ulcers suturing can not be
      oppose to traditional laparotomy; each method has own indications and
      contraindications. But mini-invasive surgical procedures may be regarded as real
      alternative to traditional open surgeries because of minimal approach, minimal
      surgical trauma and high economic effect in treatment and rehabilitation of these
      patients.

PMID- 17495834
TI  - [Selective proximal vagotomy with duodenoplasty for the treatment of ulcerous
      duodenal stenosis].
AB  - Short- and long-term results of isolated selective proximal vagotomy (SPV)
      performed at non-complicated duodenal ulcer and SPV with duodenoplastic and
      drainage surgeries at ulcerous pyloroduodenal stenosis were analyzed. Principles
      of choice of duodenoplastic and drainage surgeries are discussed. Six variants of
      duodenoplasty is used depending on anatomic characteristics and localization of
      stenosis. Advantage of duodenoplasty over drainage surgeries is demonstrated. It
      is concluded that SPV with duodenoplasty should be regarded as surgical method of
      choice at the treatment of ulcerous duodenal stenosis because of low rate of
      stomach and duodenum functional disorders at long-term period after surgery.

PMID- 17495835
TI  - [Surgical treatment at combination of duodenal ulcers with reflux-esophagitis].
AB  - Selective proximal vagotomy (SPV) was performed at 352 patients with duodenal
      ulcer (DU), 213 of them had reflux-esophagitis (RE). SPV was performed with
      correcting cardia function operations at all the patients (including ones without
      RE). It is demonstrated that SPV at combination of RE with DU is safe but
      effective surgical method and permits to achieve complete recovery from both
      diseases. SPV is radical if indications are correct and surgical technical
      requirements are fulfilled.

PMID- 17495836
TI  - [Gastroduodenoscopy at diagnosis and treatment of ulcerous gastroduodenal
      bleedings].
AB  - Results of treatment of 458 patients with ulcerous gastroduodenal bleedings are
      analyzed. It is demonstrated that argon-plasma coagulation (APC) is the most
      effective at primary endoscopic hemostasis and amounts to 92.5% compared with
      87.5% at radio-wave coagulation and 79.7% at injection method. Treatment and
      diagnostic algorithm based on patients state severity assessment (by SAPS scale)
      and risk of bleeding (by Forrest) was developed. Use of this algorithm led to
      decrease of lethality due to acute blood less from 6.1 to 2.7% (including at
      conservative treatment from 4.5 to 2.2%) and postoperative lethality from 14.5 to
      5.6%.

PMID- 17495837
TI  - [Problems of diagnosis and surgical treatment of early postoperative abdominal
      complications].
AB  - Results of treatment of 419 patients with early postoperative abdominal
      complications have been analyzed. Diagnosis of complication has been made at
      postmortem examination at 26 patients (1st group). The indications to
      relaparotomy at 165 patients (2nd group) were based on clinical and laboratory
      data. Lethality at this group was 35.8%. Complex method of diagnosis including
      special methods (laparoscopy, ultrasound) was used at 228 patients (3rd group).
      Mini-invasive surgical treatment technologies were used at 118 of them. Lethality
      at this group was 17.1%.

PMID- 17495838
TI  - [Diagnosis and prophylaxis of latent hepatic failure at patients with hepatic
      echinococcosis].
AB  - Morphological and biochemical (NAD, NADF, xanthine oxidase, lipid peroxidation
      products) disorders at liver tissue samplings were studied at 60 patients with
      hepatic echinococcosis. It is demonstrated that hydatid cysts of both lobe of
      liver are associated with high level of lipid peroxidation products and low level
      of respiratory coenzymes at liver tissue. It is concluded that morphological and
      biochemical examinations of liver tissue samplings are the main methods for early
      diagnosis of hepatic failure at patients with hepatic echinococcosis.

PMID- 17495839
TI  - [Functional state of lower extremities muscles at the patients with shin
      congenital defects before and after treatment with Ilizarov device].
AB  - Results of examination (dynamometry, electromyography, ultrasonography) of 34
      patients aged 6 to 23 years before and after treatment with Ilizarov's method are
      analyzed. Decrease of dynamometry and electromyography parameters, ultrasonic
      data are evidence of hard structural and functional disorders of motor system of
      these patients. Decrease of force and activation characteristics of tested
      muscles of operated extremity after removal of external fixator relates to high
      level of central protective inhibition and prolonged afferentation dysbalance at
      somatosensory system. Degree of recovery is limited and depends on patient age:
      recovery resources are presented at children before 8 years, but at juveniles
      they are depleted during the growth.

PMID- 17495840
TI  - [Surgical treatment of osteomyelitis defects of long bones].
AB  - Results of treatment of 116 patients with gunshot osteomyelitis are analyzed.
      Positive and negative moments of different surgical methods (sequestrnecrectomy,
      Ilizarov's method, auto- and alloplasty) are discussed. Two-stage method of
      treatment of long bones gunshot osteomyelitis (with osteoplastic surgeries after
      elimination of inflammation and before severe scarring process into tissues) is
      developed.

PMID- 17495841
TI  - [Ligature fixation of floating ribs at closed injury of chest].
AB  - Original devices (pericostal needle for passage of ligatures around ribs and
      sternum, and breast splint for ligature fixation of floating ribs) have been
      produced and patented. This method has been clinically approved at 111 patients
      with multiple fragmentary fractures of ribs. These devices made the surgical
      procedures easier and were effective at the treatment of severe closed injury of
      chest. Frame of chest is restored, severe respiratory failure is eliminated. In
      one day lung vital capacity increases in 1.5-2 times, blood oxygenation - on 12%.
      Lethality has been reduced in 3 times compared with traditional methods of
      floating ribs traction. Forty-one of 43 severe patients have been successfully
      cured.

PMID- 17495842
TI  - [Choice of optimal surgical reconstruction at patients with critical limb
      ischemia due to infrainguinal atherosclerotic arterial occlusive disease].
AB  - One hundred and four patients with atherosclerotic lesion of femoro-popliteal
      segment and III-IV stage of ischemia underwent vascular surgical procedures.
      Results of these operations were analyzed depending on state of distal arterial
      bed. Autovenous femoro-popliteal bypass (FPB) with reversed autovein was
      performed at 49 (47.1%) patients, femoro-tibial bypass (FTB) with autovein in
      situ - at 55 (52.9%). Clinical and angiographic variants of favorable and
      unfavorable prognosis of FBP and FTB are described. It is demonstrated that
      severe lesion of outflow distal arteries is the main cause of bypasses
      thrombosis. Protective arteriovenous fistula in the region of FTB distal
      anastomosis improves significantly short-term results of operation.

PMID- 17495843
TI  - [Microcirculation disorders as the cause of capsular contraction after
      augmentative mammoplasty].
AB  - Fragments of fibrous capsules removed during operations on account of III - IV
      degree fibrous capsular contraction around mammoimplant or prosthesis
      (oleoimplant) deformation were studied with light microscopy. Signs of
      lymphostasis were detected in all the layers of capsule at all the patients.
      Fibrous capsular contraction progresses due to dysbalance between volumes of
      areolar (boundary) and thick (basic) parts of capsule. This dysbalance may be
      caused by activation of inflammatory reaction at tissues surrounding implant
      after trauma of them, or by microcirculation disorders due to blockade of vessels
      with implants or tissue detritus.

PMID- 17495844
TI  - [Sensitization of lymphocytes to insulin as one of risk factors of ischemic heart
      disease].
AB  - Prevalence and character of sensitization of lymphocytes to insulin and its
      prognostic significance were studied in 71 patients with ischemic heart disease
      and 55 healthy people. Direct overt sensitization of lymphocytes to insulin was
      found in 14 of 71 patients (p<0.01 compared with control group). This type of
      reaction was associated with myocardial infarction. Concealed indirect reaction
      of lymphocytes to insulin was revealed at inhibition of cells with receptors to
      histamine or prostaglandin synthesizing cells in 13 and 19 of 71 patients,
      respectively (p<0.01 and p<0.05 compared with control group). Direct overt
      sensitization of lymphocytes to insulin and concealed indirect sensitization
      revealed at inhibition of functional activity of cells with receptors to
      histamine serve as prognostically unfavorable factors because they are associated
      with development of heart failure and higher rate of lethal outcome.

PMID- 17495845
TI  - [Ischemic heart disease in patients with schizophrenia (clinico-epidemiological
      study)].
AB  - We carried out a multicenter controlled study of case histories of patients with
      schizophrenia and acute myocardial infarction (AMI) or postinfarction
      cardiosclerosis (PIC) from cardiological (n=44), psychosomatic (n=19) and
      psychiatric (n=23) hospitals was. In hospital mortality, ischemic heart disease
      (IHD) risk factors, peculiarities of IHD course, antipsychotic therapy were
      analyzed. Elevation of in hospital mortality related to PIC and its complications
      was revealed in somatopsychiatric (21% vs 1.26%; p<0.05) and psychiatric (29% vs
      1.26%; p<0.05) hospitals. Hypercholesterolemia, excess weight in patients with
      schizophrenia were met more rarely (36, 32, 9, 21%, 16, 0% vs 61, 45%,
      respectively; p<0.05) while diabetes mellitus (5, 5, 9% vs 15%, respectively;
      p>0.05), arterial hypertension (89, 84, 45% vs 77%, respectively; p>0.05) - with
      same frequency as in comparison group. Patients with schizophrenia do not differ
      from persons not suffering from this psychiatric disease by proportion of
      patients with AMI (39, 47, 49% vs 43%; p>0.05) and PIC (73, 74, 61% vs 73%;
      p>0.05). Probability of effect of inadequate body weight and psychotherapy with
      phenothiazine derivatives and antiparkinsonian cholinolytic medications on
      elevation of mortality of patients with IHD and schizophrenia is discussed.

PMID- 17495846
TI  - [Cytotoxic effect of lymphocytes with cardiolipin in diagnosis of acute coronary
      syndrome].
AB  - Cytotoxic effect of lymphocytes sensitized to cardiolipin antigen was studied in
      172 patients with acute coronary syndrome. In this phenomenon effector cells were
      peripheral blood T-lymphocytes and target cells were erythrocytes loaded with
      cardiolipin antigen. It was found that cytotoxic effect of lymphocytes in these
      patients carries diagnostic information and can have supplementary value in
      difficult cases of diagnostics of this disease.

PMID- 17495847
TI  - [Clinico-epidemiological program of the study of depression in cardiological
      practice in patients with arterial hypertension and ischemic heart disease
      (COORDINATA)].
AB  - COORDINATA - first Russian multicenter prospective (3 year long) study having the
      aim to elucidate prevalence of symptoms of anxiety and depression among patients
      with arterial hypertension (AH) and ischemic heart disease (IHD) and their
      influence on cardiovascular (CV) prognosis. Results of baseline epidemiological
      part of the study are presented. Results of prospective phase will be published
      in 2008. MATERIAL AND METHODS: Symptoms of depression and anxiety were assessed
      by validated in Russia Hospital Anxiety and Depression Scale (HDS) in 5038
      patients with AH and/or IHD aged 55 years and older. Prevalence of CV risk
      factors was also studied and their association with anxiety/depressive symptoms
      were evaluated in a framework of multivariate regression analysis. RESULTS:
      Clinically significant symptoms of anxiety (HADS score >or=11) took place in 33
      and 38%, symptoms of depression - in 30 and 38% of patients with AH and IHD,
      respectively. Relationship of symptoms of anxiety and depression was established
      with a number of psychosocial and biological risk factors of CV diseases (D)
      specifically low levels of education and income, insufficient level of physical
      activity, high level of chronic psychoemotional stress, exposition to acute
      stresses of great power, lack of social support, social isolation, elevated blood
      pressure level. It was shown that CVD comorbid anxiety and depressive states
      might cause excessive use of health care resources by patients.

PMID- 17495848
TI  - [Problems of a physician-patient interaction and control of arterial hypertension
      in Russia. Main results of scientific-practical program ARGUS-2].
AB  - OBJECTIVE: To study the problems of physician-patient cooperation, patient- and
      physician related barrieres to target blood pressure (BP) achievement and to
      demonstrate improvement of BP control with indapamide SR 1.5 mg, when given to
      patients remaining uncontrolled while receiving antihypertensive therapy without
      thiazide diuretics (TD). METHODS: The trial Improvement of Arterial Hypertension
      Control in High-Risk Hypertensive Patients (ARGUS-2) run in 15 Russian centres
      during the year 2006. Retrospective analysis of medical notes of 684 outpatients
      and 575 inpatients with arterial hypertension. Validated questionnaires were used
      for interview of 373 physicians and 1298 patients. The study of Arifon retard
      efficacy was carried out in 1438 outpatients with difficult-to-control
      hypertension. RESULTS: BP was above the goal level in 97.1% pts at the first
      analyzed visit to an outpatient department. Antihypertensive therapy was
      unchanged in 20.5% cases, the drug dose was increased in 46,6%, additional
      medication was administered in 36,8%. In 30.8% pts antihypertensive agent was
      substituted by another class drug. At the last analyzed visit target BP was found
      in 24.4% pts. BP control was poorer in pts with BP goal <130/80 mmHg (20.1%) than
      in those with higher target BP (25.9%). Achievement of BP goal was associated
      with combination therapy, higher rate of TD administration and with more frequent
      visits to physician. During hospitalization target BP <140/<90 mmHg was achieved
      in 87.1%,<130/<80 mmHg in. 76.2%. Arifon retard administration resulted in target
      BO achievement in 84.5% patients. Physicians percept low adherence to
      antihypertensive treatment, lack of patients knowledge about risk related to
      arterial hypertension, economical problems as main barriers to improvement of
      arterial hypertension management. Patients considered economical problems related
      to antihypertensive treatment more much less important than physicians did.
      CONCLUSION: The study results suggest the importance of therapeutic inertia
      overcome to improve arterial hypertension management in Russia. Low rate of
      multiple combination therapy and TD prescription are important features of
      therapeutic inertia. Polar perception of problems related to arterial
      hypertension by physicians and patients should be considered as influencing
      factors for educational programs development.

PMID- 17495849
TI  - [The efficacy and safety of nibentan for pharmacological cardioversion in
      patients with persistent atrial fibrillation and flutter: the role of dose
      limitation and magnesium sulfate administration].
AB  - The aim of the study was to evaluate the influence of magnesium sulfate on the
      efficacy and safety of pharmacological cardioversion with nibentan (NB) in doses
      up to 0,125 mg/kg in patients with persistent atrial fibrillation (AF) and
      flutter (AFL). Calculated dose of NB was 0.125 mg/kg. It was administered as 2
      bolus injections (0.0625 mg/kg each) performed with the interval of 15 minutes.
      The study included 64 patients (pts) (45 male, age 54+/-9,9 years) with
      persistent AF (n=56) and AFL (n=8) with median arrhythmia duration 6,7+/-6,8
      months (8 days to 36 months). Pts were divided into two groups. In the first (I)
      group NB was used without preliminary magnesium sulfate administration, in the
      second group (II) magnesium sulfate was injected in a dose of 50 mg/kg, followed
      by 0.83 mg/kg/min infusion before NB administration. There was no difference
      between groups in conversion rates of atrial arrhythmias: 74% and 69%, in groups
      I and II, respectively (p>0.4). Mean effective dose of NB was the same in
      investigated groups - 0.09 mg/kg. Administration of initial dose of NB (0.0625
      mg/kg) converted AF/AFL to sinus rhythm within 15-min interval in 29.7% of
      patients. Efficacy of full dose of NB (0.125 mg/kg) was 100% in AFL, 68% in AF.
      No side effects were registered after initial injection of 0.0625 mg/kg. After
      administration of 2 boluses (0.125 mg/kg) "torsade de pointes" developed in 2 pts
      (3%). Magnesium sulfate administration had no influence on NB efficacy and rate
      of its proarrhythmic events. Limitation of NB total dose to <or= 0.125 mg/kg
      divided into 2 bolus injections does not lead to loss of antiarrhythmic efficacy
      and makes its administration more safe.

PMID- 17495850
TI  - [Chronic asymptomatic hyperuricemia as a marker of atherogenic risk in children].
AB  - A cross-sectional study of a representative sample of boys aged 7-17 years
      (n=569) was carried out in Arkhangelsk. The rate of asymptomatic hyperuricemia
      was 27.59 %. Serum level of uric acid correlated with levels of triglycerides,
      total cholesterol, low density lipoprotein cholesterol, fasting glycemia,
      systolic and diastolic blood pressure (r = 0.49; 0.27; 0.27; 0.26; 0.34 u 0.35,
      respectively; p<0,05). Prevalence of borderline and pronounced hyperlipidemia,
      elevated blood pressure, and impaired fasting glycemia among children with
      elevated uric acid level was higher than among children with normal level of uric
      acid. Chronic asymptomatic hyperuricemia in childhood can be regarded as marker
      of atherogenic risk because of its association with atherogenic phenotype of
      lipids and lipoproteins levels, increased fasting glycemia and elevated blood
      pressure.

PMID- 17495851
TI  - [Pulmonary hypertension and right ventricular failure. Part VIII. Diagnosis,
      course, and prognosis of primary (idiopathic) 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 eight communication they describe presentations of PH and
      methods of its instrumental diagnostics. This part also contains discussion of
      problems of differential diagnosis of diseases which can be complicated by PH,
      contemplation of natural course of primary (idiopathic) PH and factors
      determining its prognosis.

PMID- 17495852
TI  - [Compliance to treatment of arterial hypertension and ischemic heart disease -
      key condition of lowering of cardiovascular mortality].
AB  - The paper contains consideration of the problem of compliance to treatment of
      arterial hypertension and ischemic heart disease. Various aspects of compliance
      to treatment related to patients, physicians, special features of diseases and
      character of drug and nondrug recommendations.

PMID- 17495853
TI  - Microinjection and electroporation of embryonic kidney explants: an improved
      method.
AB  - Embryonic kidney explants are routinely used to study the molecular regulation of
      kidney development. One of the major technical challenges has been the need to
      express transgenes at high levels for prolonged periods of time. Existing
      protocols derived from work with the chick have used microinjection and
      electroporation with low voltage and long pulse time. In this study, we show that
      a high voltage with a short pulse time is preferable for mouse kidney explants.
      Using these conditions, gene expression is enhanced 10-fold over a 96-h period in
      culture with minimal toxicity. Furthermore, by modifying the site of
      microinjection, the ureteric bud or the metanephric mesenchyme can be targeted.
      We suggest that our described conditions will make microinjection and
      electroporation a more effective method to study gene function in the developing
      mouse kidney.

PMID- 17495854
TI  - Gender-specific effects of endogenous testosterone: female alpha-estrogen
      receptor-deficient C57Bl/6J mice develop glomerulosclerosis.
AB  - Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis
      (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates
      while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly
      mutant mice on an ROP background. To explore the effects of sex hormones on
      glomerular structure and function in the context of gender and genetic
      background, we studied mice in which the estrogen-receptor (ER) genes alpha- or 
      beta were deleted (alpha- or betaER knockout (KO)) and crossed into the B6
      background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male
      and female betaERKO and male alphaERKO mice had no glomerular dysfunction at 9
      months of age; however, alphaERKO female mice displayed albuminuria and GS. Ovx
      prevented glomerular dysfunction in alphaERKO female mice by eliminating
      endogenous testosterone production while exogenous testosterone induced GS in Ovx
      B6 mice. Androgen receptor (AR) expression and function was found in
      microdissected glomeruli and cultured mesangial cells. Testosterone compared to
      placebo increased both AR expression and TGF-beta1 mRNA levels in glomeruli
      isolated from female B6 mice. Estrogen deficiency had no deleterious effects on
      the glomeruli in B6 mice. Our study shows that genetic traits strongly influence
      the GS-promoting effects of estrogen deficiency while testosterone induces GS in
      a gender-specific manner.

PMID- 17495855
TI  - Microsomal prostaglandin E synthase-1 and blood pressure regulation.
AB  - Prostaglandin E (PGE)(2) is a major arachidonic acid metabolite in a wide variety
      of tissues and is implicated in the control of inflammatory as well as
      physiological responses. At least three major forms of PGE synthase (PGES) have
      recently been cloned and characterized: membrane-associated PGES (mPGES)-1, mPGES
      2, and cytosolic PGES (cPGES). Among them, mPGES-1 is highly inducible by
      cytokine and is critically involved in pain and inflammatory responses. Emerging
      evidence suggests that mPGES-1 may also participate in blood pressure (BP)
      regulation through an impact on renal and vascular functions. Within the kidney,
      mPGES-1 predominates in the distal nephron where its expression is highly
      inducible by salt loading. Mice lacking mPGES-1 exhibit blunted natriuretic
      response paralleled with remarkably suppressed nitric oxide production, leading
      to salt-sensitive hypertension. These mice also exhibit an exaggerated
      hypertensive response to angiotensin II infusion. Together, these results suggest
      that mPGES-1 may be an important physiological regulator of BP.

PMID- 17495856
TI  - Fibrocytes: a new insight into kidney fibrosis.
AB  - Fibrocytes are supposed to be a circulating connective tissue cell progenitor,
      which consists of a novel population of peripheral blood cells. This distinct
      population of blood-borne cells shares markers of leukocytes as well as
      mesenchymal cells. Accumulating evidence indicates that fibrosis is
      characteristic of progressive chronic kidney diseases of any etiologies,
      resulting in kidney failure. We have uncovered that CCR7-positive fibrocytes
      migrate into the kidney in response to secondary lymphoid tissue chemokine
      (SLC/CCL21) and contribute to kidney fibrosis induced by unilateral ureteral
      obstruction in mice. In addition, the blockade of CCL21/CCR7 signaling by anti
      CCL21 antibodies reduced kidney fibrosis, which was confirmed by a decrease in
      fibrosis in CCR7-null mice with concomitant reduction in macrophage recruitment
      along with reduced renal transcripts of monocyte chemoattractant protein-1 (MCP
      1/CCL2). These findings suggest that fibrocytes dependent on CCL21/CCR7 signaling
      pathways contribute to the pathogenesis of kidney fibrosis, thereby providing
      that regulating fibrocytes may provide a novel therapeutic benefit for kidney
      fibrosis.

PMID- 17495857
TI  - Organic cation transport in the rat kidney in vivo visualized by time-resolved
      two-photon microscopy.
AB  - Secretion of cationic drugs and endogenous metabolites is a major function of the
      kidney accomplished by tubular organic cation transport systems. A cationic
      styryl dye (ASP(+)) was developed as a fluorescent substrate for renal organic
      cation transporters. The dye was injected intravenously and continuously
      monitored in externalized rat kidneys by time-resolved two-photon laser scanning
      microscopy. To investigate changes in transport activity, cimetidine, a
      competitive inhibitor of organic cation transport was co-injected with ASP(+).
      Shortly after injection, fluorescence increased in peritubular capillaries.
      Simultaneously, fluorescence was transiently found at the basolateral membrane of
      the proximal and distal tubules at a higher intensity and shorter wavelength
      indicating membrane association of ASP(+). Subsequently, intracellular
      fluorescence increased steeply within 10 s. In the proximal tubules,
      intracellular fluorescence decreased by 50% within 5 min, while in the distal
      tubules the fluorescence decreased by only 5% within the same time frame.
      Intracellular uptake of ASP(+) into proximal tubules was significantly reduced by
      cimetidine. Our studies show that organic cation transport of the kidney can be
      visualized in vivo by two-photon laser scanning microscopy.

PMID- 17495858
TI  - The endothelial cell in ischemic acute kidney injury: implications for acute and
      chronic function.
AB  - Recent evidence suggests that injury to the renal vasculature may play an
      important role in the pathogenesis of both early and chronic ischemic acute
      kidney injury (AKI). Established and new data support the suggestion that
      vascular injury, in particular, endothelial cell injury, participates in the
      extent and maintenance of AKI by pathways that are related to vascular tone.
      Early alterations in peritubular capillary blood flow during reperfusion has been
      documented and associated with loss of normal endothelial cell function, which
      can be replaced pharmacologically or with cell replacement interventions.
      Distorted peritubular capillary morphology is associated with loss of barrier
      function that may contribute to early alterations in vascular stasis. In
      addition, ischemia induces alterations in endothelial cells that may promote
      inflammation and procoagulant activity, thus contributing to vascular congestion.
      Reductions in microvasculature density may play a critical part in the
      progression of chronic kidney disease following initial recovery from
      ischemia/reperfusion-induced AKI. The exact nature of how capillary loss alters
      renal function and predisposes renal disease is thought to be due at least in
      part to hypoxia. Finally, the loss of endothelial cell function may represent an
      important therapeutic target in which nitric oxide, vascular trophic support,
      and/or endothelial progenitor cells may show potential importance in ameliorating
      the acute and/or chronic effects of ischemic AKI.

PMID- 17495859
TI  - Prenatal programming of nephron number and blood pressure.
AB  - A low nephron number has been advocated to explain the association between
      intrauterine growth restriction (IUGR) and hypertension in later life. IUGR not
      only leads to a low birth weight but is also hypothesized to reprogram
      nephrogenesis, which results in a low nephron endowment. Several methods are used
      to estimate the total glomerular number, but only stereological techniques result
      in accurate (unbiased) and precise (reproducible) data. Several studies, both in
      humans and animal models that have used these methods indeed revealed that IUGR
      leads to a low nephron number. According to the hyperfiltration hypothesis, this
      reduction in renal mass is supposed to lead to glomerular hyperfiltration and
      hypertension in remnant nephrons with subsequent glomerular injury with
      proteinuria, systemic hypertension and glomerulosclerosis. Even though IUGR is
      associated with both a low nephron endowment and an increased risk of
      hypertension, only circumstantial evidence is available to support the
      hyperfiltration hypothesis after prenatal programming. A prerequisite for
      establishment of this association in long-term, prospective follow-up studies is
      the ability to estimate glomerular numbers in living human beings, for which a
      further advancement in radiological techniques is necessary. Only then can the
      association between nephron endowment and blood pressure in humans be studied
      more conclusively.

PMID- 17495860
TI  - Amylin deposition in the kidney of patients with diabetic nephropathy.
AB  - Amylin (islet amyloid peptide) plays a critical role in islet amyloidosis and in
      the development of beta-cell dysfunction in patients with diabetes; however, the
      involvement of amylin in renal amyloidosis has not been studied. For this reason,
      we surveyed 149 patients with biopsy-proven diabetic nephropathy (DN). The
      results were compared to 95 renal disease control patients, which included
      membranoproliferative glomerulonephritis, light-chain deposition, IgA
      nephropathy, and obesity-related glomerulopathy (ORG). Seventy-two of the 149
      patients with DN showed amylin deposition in their renal tissue. Amylin was
      mainly distributed in the expanded mesangial area, Kimmelstiel-Wilson nodules,
      Bowman's capsule, and in blood vessels. The frequencies of mesangial
      proliferation, glomerular nodule lesions, and glomerular sclerosis were higher in
      DN patients with amylin deposits. Furthermore, the tubular interstitial lesions
      were more severe in these patients. Of the 95 disease-control patients, four with
      ORG were positive for renal amylin deposits. Our study has found renal amylin
      deposition in patients with DN and that the deposition was associated with
      disease severity. We suggest that strict metabolic control and reversing insulin
      resistance in patients with diabetes may blunt the process of amylin deposition
      in the kidney and possibly protect renal function in these patients.

PMID- 17495861
TI  - A role of liver fatty acid-binding protein in cisplatin-induced acute renal
      failure.
AB  - Previous studies from our laboratory showed that increased fatty acid oxidation
      by the kidney is cytoprotective during cisplatin (CP)-mediated nephrotoxicity. In
      this study, we determined the effects of CP and fibrates on peroxisome
      proliferation and the expression of liver fatty acid-binding protein (L-FABP) in
      normal mice, and in mice transgenically overexpressing human L-FABP (h-L-FABP).
      Labeling of peroxisomes demonstrated reduced peroxisomal staining in the proximal
      tubule of CP-treated mice compared with control mice. There was increased
      peroxisomal labeling in the proximal tubules of both control and CP-treated mice
      when either was treated with fibrate; a known peroxisome proliferator-activated
      receptor-alpha ligand. L-FABP protein expression, not detected in control or CP
      treated mice, was significantly increased in the proximal tubules of fibrate
      treated mice of either group. In the transgenic mice, CP increased the shedding
      of h-L-FABP in the urine, which was decreased by fibrate as was the acute renal
      failure. A cytosolic pattern of h-L-FABP expression was found in the proximal
      tubules of untreated transgenic mice with a nuclear presence in CP-treated mice.
      Fibrate pretreatment restored the cytosolic expression pattern in CP-treated
      mice. Our study shows that fibrate may improve CP-induced acute renal failure due
      to both peroxisome proliferation and increased L-FABP in the cytosol of the
      proximal tubule.

PMID- 17495862
TI  - Post-renal acute renal failure.

PMID- 17495863
TI  - Th1 polarization in murine IgA nephropathy directed by bone marrow-derived cells.
AB  - IgA nephropathy is the most common form of progressive glomerulonephritis
      although the pathophysiology of this nephropathy is unclear. The ddY mouse is a
      spontaneous animal model with variable incidence and extent of glomerular injury
      mimicking human IgA nephropathy. Here, we transplanted bone marrow cells from 20
      week-old ddY mice with beginning or quiescent IgA nephropathy into irradiated
      similar ddY mice, C57Bl/6 (Th1 prone) mice, or BALB/c (Th2 prone) mice. Serum
      IgA/IgG complex and Th1/Th2 polarization of spleen cells was determined by enzyme
      linked immunosorbent assay and confirmed by fluorescent cytometric analysis. The
      ddY mice with commencing IgA nephropathy demonstrated strong polarization toward
      Th1, while those with quiescent disease were Th2 polarized. Serum levels of
      IgA/IgG2a immune complex significantly correlated with the severity of the
      glomerular lesions. Bone marrow taken from mice with commencing IgA nephropathy
      conferred IgA nephropathy with Th1 polarization in recipient-quiescent mice,
      while transplantation from the quiescent mice ablated glomerular injury and
      mesangial IgA/IgG deposition in those commencing IgA disease. However, adoptive
      transfer of CD4(+) T cells from those whose disease began failed to induce any
      IgA deposition or renal injury. Our study suggests that bone marrow cells,
      presuming IgA producing cells, may initiate this disease. Th1 cells may be
      involved in the pathophysiology of the disease after glomerular IgA deposition.

PMID- 17495864
TI  - Different roles of TiR8/Sigirr on toll-like receptor signaling in intrarenal
      antigen-presenting cells and tubular epithelial cells.
AB  - Toll-like receptors (TLRs) exist on both myeloid and intrinsic renal cells
      contributing to the initiation of innate immunity during renal infection with
      uropathogenic Escherichia coli. Toll-interleukin 1 receptor (IL-1R) (TIR)8/SIGIRR
      is an orphan receptor of the TLR/IL-1R family, which suppresses TLR signaling of
      immune cells and is highly expressed in the kidney. Lack of TIR8/SIGIRR is
      associated with enhanced renal chemokine signaling upon exposure to
      lipopolysaccharide (LPS). This was because of TIR8/SIGIRR expression on resident
      intrarenal myeloid cells rather than tubular epithelial cells which express it on
      basolateral and luminal membranes. The lack of TIR8/SIGIRR does not enhance
      TLR/IL-1R signaling in tubular epithelial cells as was observed in monocytes.
      TIR8/SIGIRR is induced in monocytes treated with LPS or tumor necrosis factor and
      interferon-gamma in a dose-dependent manner but was downregulated in treated
      tubule epithelial cells. This cell type-specific regulation and function did not
      relate to mRNA splice variants but was associated with N- and O-glycosylation of
      the receptor in renal cells of myeloid and nonmyeloid origin. Our studies show
      that resident myeloid cells contribute to TLR-mediated antimicrobial immunity in
      the kidney and that this function is controlled by Tir8/sigirr. TIR8/SIGIRR does
      not suppress TLR signaling in tubular epithelial cells, which supports their role
      as sensors of microbial infection in the kidney.

PMID- 17495865
TI  - Specific glycosaminoglycans promote unseeded amyloid formation from beta2
      microglobulin under physiological conditions.
AB  - Dialysis-related amyloidosis (DRA) is a complication of hemodialysis where beta2
      microglobulin (beta2m) forms plaques mainly in cartilaginous tissues. The tissue
      specific deposition, along with a known intransigence of pure beta2m to form
      fibrils in vitro at neutral pH in the absence of preformed fibrillar seeds,
      suggests a role for factors within cartilage in enhancing amyloid formation from
      this protein. To identify these factors, we determined the ability of a
      derivative lacking the N-terminal six amino acids found in ex vivo beta2m amyloid
      deposits to form amyloid fibrils at pH 7.4 in the absence of fibrillar seeds. We
      show that the addition of the glycosaminoglycans (GAGs) chrondroitin-4 or 6
      sulfate to fibril growth assays results in the spontaneous generation of amyloid
      like fibrils. By contrast, no fibrils are observed over the same time course in
      the presence of hyaluronic acid, a nonsulfated GAG that is abundant in
      cartilaginous joints. Based on the observation that hyaluronic acid has no effect
      on fibril stability, while chrondroitin-6-sulfate decreases the rate of fibril
      disassembly, we propose that the latter GAG enhances amyloid formation by
      stabilizing the rare fibrils that form spontaneously. This leads to the
      accumulation of beta2m in fibrillar deposits. Our data rationalize the joint
      specific deposition of beta2m amyloid in DRA, suggesting mechanisms by which
      amyloid formation may be promoted.

PMID- 17495866
TI  - Leprecan distribution in the developing and adult kidney.
AB  - The temporal and spatial deposition of extracellular matrix proteins is critical
      for nephrogenesis and glomerular maturation. We previously characterized leprecan
      as a novel chondroitin sulfate proteoglycan which has been recently shown to have
      prolyl hydroxylase activity. In this study, we examine the distribution of
      leprecan during nephrogenesis and after a hypertrophic stimulus to the adult
      kidney. During development, leprecan was localized to mesenchymal aggregates,
      early comma- and S-phase structures as determined by immunohistochemistry and in
      situ hybridization. Leprecan mRNA was increased in cells around the vascular
      cleft of the S- and comma-phase glomeruli. Expression was found in podocytes,
      mesangial cells, and parietal epithelial cells of loop-phase glomeruli. Leprecan
      mRNA was substantially decreased in the glomeruli of the adult kidney compared to
      the developing kidney with a uniform distribution between the glomeruli and the
      tubules. Within adult glomeruli, leprecan was found in the mesangium mesangial
      matrix, podocytes, and in Bowman's capsule. In response to glomerular
      hypertrophy, produced by unilateral nephrectomy, leprecan synthesis was increased
      in the adult kidney. We suggest that the regulated expression of leprecan during
      glomerular development or hypertrophy coupled with its reported prolyl
      hydroxylase activity plays a role during basement membrane assembly.

PMID- 17495867
TI  - HMG-CoA reductase inhibitors and the kidney.
AB  - During the last two decades, numerous studies have demonstrated that 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors (statins) diminish the risk of
      cardiovascular morbidity and mortality. Although these studies have focused
      primarily on the ability of statins to lower circulating levels of low-density
      lipoprotein cholesterol, more recent research has shown that statins may protect
      the vasculature via pleiotropic effects not directly related to lipid lowering.
      These include adjustments in cell-signaling pathways that play a role in
      atherogenesis and that affect the expression of inflammatory elements, curtail
      oxidative stress, and enhance endothelial function. More recently, researchers
      have begun to explore whether these agents exert similar beneficial effects in
      renal parenchymal and renovascular disease. This review examines the available
      evidence that dyslipidemia may augment the inflammatory reaction of cytokines in
      patients with renal disease and that statins may improve renal dysfunction by
      altering the response of the kidney to dyslipidemia, even in persons with end
      stage renal disease on dialysis or with renal transplantation. In this context,
      some data suggest that statin-mediated alterations in inflammatory responses and
      endothelial function may reduce proteinuria and the rate of progression of kidney
      disease.

PMID- 17495868
TI  - Making sense of human biomonitoring data: findings and recommendations of a
      workshop.
AB  - The ability to measure chemicals in humans (often termed biomonitoring) is far
      outpacing the ability to interpret reliably these data for public health
      purposes, creating a major knowledge gap. Until this gap is filled, the great
      promise of routinely using biomonitoring data to support decisions to protect
      public health cannot be realized. Research is needed to link biomonitoring data
      quantitatively to the potential for adverse health risks, either through
      association with health outcomes or using information on the concentration and
      duration of exposure, which can then be linked to health guidelines. Developing
      such linkages in the risk assessment paradigm is one of the primary goals of the
      International Council of Chemical Associations' (ICCA) Long-Range Research
      Initiative (LRI) program in the area of biomonitoring. Therefore, ICCA sponsored
      a workshop to facilitate development of a coordinated agenda for research to
      enable an improved interpretation of human biomonitoring data. Discussions
      addressed three main topics: (1) exploration of the link between exposure, dose,
      and human biomonitoring data, (2) the use of computational tools to interpret
      biomonitoring data, and (3) the relevance of human biomonitoring data to the
      design of toxicological studies. Several overarching themes emerged from the
      workshop: (a) Interpretation and use of biomonitoring data should involve
      collaboration across all sectors (i.e., industry, government, and academia) and
      countries. (b) Biomonitoring is not a stand-alone tool, and it should be linked
      to exposure and toxicological dose information. (c) Effective communication is
      critical, because when uncertainty about the actual risks is high, the perceived
      risks grow in the absence of communication. (d) The scope of future biomonitoring
      activities encompasses a variety of research approaches - from advancing the
      science to fill data gaps to advancing the accessibility of the current knowledge
      to enable better information sharing.

PMID- 17495869
TI  - Pesticide loadings of select organophosphate and pyrethroid pesticides in urban
      public housing.
AB  - We investigated the magnitude and distribution of pyrethroid and organophosphate
      pesticide loadings within public housing dwellings in Boston, Massachusetts and
      compared the results using various sampling methods. We collected dust matrices
      from living room and kitchen in 42 apartments and analyzed for eleven pyrethoids
      (e.g., permethrin and cyfluthrin) and two organophosphates (chlorpyrifos and
      diazinon) in house dust using GC/MS. Agreement between sampling methods were
      evaluated using Spearman correlations and Kappa statistics. Permethrin and
      chlorpyrifos were detected in kitchen floor wipes in all homes, followed in
      frequency of detects by diazinon (98%), cypermethrin (90%) and cyfluthrin (71%).
      At least six pesticides were detected in kitchen floor wipes in the majority of
      the homes (range 3-8). Positive and statistically significant correlations among
      dust matrices were observed between kitchen floor wipes and living room vacuum
      dust, including for diazinon (r=0.62) and cyfluthrin (r=0.69). Detection of
      several pesticides including banned or restricted use products in some public
      housing units, underscore the need for alternative pest management strategies
      that embrace the safe and judicious use of pest control products.

PMID- 17495870
TI  - Scientific governance and the process for exposure scenario development in REACH.
AB  - The primary process established by the European Commission to address the science
      needed to define key REACH concepts and to help rationally implement REACH's
      ambitions is enshrined in a series of activities known as the REACH
      Implementation Projects (RIPs). These are projects that aim to define the
      methodology that could be used, and present the basis for guidance on the actual
      principles and procedures that may be (are proposed to be) followed in the
      development of the required documentation that ensures the safe use of chemicals.
      In order to develop soundly based and equitable regulation, it is necessary that
      science governance using established and accepted scientific principles must take
      a leading role. The extent to which such governance is embraced will be
      determined by many factors, but notably the process adopted to enable scientific
      discussion to take place. This article addresses the issues of science as they
      have impacted on the exemplification of the Exposure Scenario concept under
      REACH. The current RIP activities have created a non-adversarial process in which
      the key stakeholders are able to discuss the key REACH challenges. But the RIP
      activities will be finalised before REACH comes into force. A suitable mechanism
      should perhaps now be identified to ensure that this positive spirit of
      scientific discussion and collaboration can continue to benefit REACH and those
      that it serves well into the future.

PMID- 17495871
TI  - Cumulative asbestos exposure for US automobile mechanics involved in brake repair
      (circa 1950s-2000).
AB  - We analyzed cumulative lifetime exposure to chrysotile asbestos experienced by
      brake mechanics in the US during the period 1950-2000. Using Monte Carlo methods,
      cumulative exposures were calculated using the distribution of 8-h time-weighted
      average exposure concentrations for brake mechanics and the distribution of job
      tenure data for automobile mechanics. The median estimated cumulative exposures
      for these mechanics, as predicted by three probabilistic models, ranged from 0.16
      to 0.41 fibers per cubic centimeter (f/cm(3)) year for facilities with no dust
      control procedures (1970s), and from 0.010 to 0.012 f/cm(3) year for those
      employing engineering controls (1980s). Upper-bound (95%) estimates for the 1970s
      and 1980s were 1.96 to 2.79 and 0.07-0.10 f/cm(3) year, respectively. These
      estimates for US brake mechanics are consistent with, but generally slightly
      lower than, those reported for European mechanics. The values are all
      substantially lower than the cumulative exposure of 4.5 f/cm(3) year associated
      with occupational exposure to 0.1 f/cm(3) of asbestos for 45 years that is
      currently permitted under the current occupational exposure limits in the US.
      Cumulative exposures were usually about 100- to 1,000-fold less than those of
      other occupational groups with asbestos exposure for similar time periods. The
      cumulative lifetime exposure estimates presented here, combined with the negative
      epidemiology data for brake mechanics, could be used to refine the risk
      assessments for chrysotile-exposed populations.

PMID- 17495872
TI  - Ambient particle source apportionment and daily hospital admissions among
      children and elderly in Copenhagen.
AB  - An association between particulate air pollution and morbidity and mortality is
      well established. However, little is known about which sources of particulate
      matter contribute most to the adverse health effects. Identification of
      responsible sources would merit more efficient control. For a 6-year period (01
      January 1999 to 31 December 2004), we examined associations between urban
      background PM(10) in the presence of gaseous pollutants (CO, NO(2)) and hospital
      admissions due to cardiovascular and respiratory disease in the elderly
      (age>/=65), and asthma in children (age 5-18) in Copenhagen, Denmark. We further
      studied associations between fractions of PM(10) assigned to six sources
      (biomass, secondary, oil, crustal, sea salt, and vehicle) and admissions during a
      1(1/2) -year campaign. We used Poisson generalized additive time-series model
      adjusted for season, day of the week, public holidays, influenza epidemics, grass
      pollen, school holidays, and meteorology, with up to 5 days lagged air pollution
      exposure. We found positive associations between PM(10) and the three health
      outcomes, with strongest associations for asthma. The PM(10) effect remained
      robust in the presence of CO and NO(2). We found different PM(10) sources to be
      variably associated with different outcomes: crustal and secondary sources showed
      strongest associations with cardiovascular, biomass with respiratory, and vehicle
      with asthma admissions. These novel results may merit future research of
      potential mechanism, whereas at present, no single PM(10) source can be
      attributed to all morbidity.

PMID- 17495873
TI  - Time for quantitative clinical pharmacology: a proposal for a pharmacometrics
      curriculum.
AB  - A formal training program in pharmacometrics is essential to train clinical
      pharmacology scientists. A proposal is made for a pharmacometrics curriculum. The
      curriculum has components at the undergraduate, graduate and postgraduate levels.

PMID- 17495875
TI  - The current state of knowledge on age, sex, and their interactions on clinical
      pharmacology.
AB  - Pharmacokinetic and pharmacodynamic changes occur with increasing age. Sex
      differences in pharmacokinetics and pharmacodynamics exist and persist at older
      age. The issue for the clinician is how to best treat the older patient with
      currently available knowledge. This communication highlights age- and sex-related
      differences in pharmacokinetics that should influence clinical practice and
      prescribing guidelines to optimize clinical responses. The most compelling data
      for sex-specific medication dosing guidelines for older patients are related to
      volume of distribution differences, or size differences, between the sexes and to
      differences in glomerular filtration rates.

PMID- 17495874
TI  - Contribution of itraconazole metabolites to inhibition of CYP3A4 in vivo.
AB  - Itraconazole (ITZ) is metabolized in vitro to three inhibitory metabolites:
      hydroxy-itraconazole (OH-ITZ), keto-itraconazole (keto-ITZ), and N-desalkyl
      itraconazole (ND-ITZ). The goal of this study was to determine the contribution
      of these metabolites to drug-drug interactions caused by ITZ. Six healthy
      volunteers received 100 mg ITZ orally for 7 days, and pharmacokinetic analysis
      was conducted at days 1 and 7 of the study. The extent of CYP3A4 inhibition by
      ITZ and its metabolites was predicted using this data. ITZ, OH-ITZ, keto-ITZ, and
      ND-ITZ were detected in plasma samples of all volunteers. A 3.9-fold decrease in
      the hepatic intrinsic clearance of a CYP3A4 substrate was predicted using the
      average unbound steady-state concentrations (C(ss,ave,u)) and liver microsomal
      inhibition constants for ITZ, OH-ITZ, keto-ITZ, and ND-ITZ. Accounting for
      circulating metabolites of ITZ significantly improved the in vitro to in vivo
      extrapolation of CYP3A4 inhibition compared to a consideration of ITZ exposure
      alone.

PMID- 17495876
TI  - Patient-reported adverse events under asthma therapy: a community pharmacy-based
      survey.
AB  - The characteristics of patients who report adverse events (AEs) attributed to
      asthma therapy have been little investigated. Asthma patients aged 18-50 years
      were surveyed in pharmacies. Patients completed a questionnaire linked to
      computerized records of dispensed medications. Patients reported all AEs that
      they attributed to asthma therapy. The correlates of reporting 2+ AEs were
      identified. Almost 59% of the 1,351 patients (mean age: 37, 56% females)
      attributed AEs to asthma therapy, and 35% at least two. Most common AEs included
      tiredness (21.8%) and palpitations (21.1%). Poor asthma control and perception of
      asthma as a handicap were the major correlates of reporting 2+ AEs (odds ratio
      (OR)=2.5, 95% confidence interval (CI)=[1.7-3.7] and OR=1.9, 95% CI=[1.4-2.5]).
      Other significant correlates included age >30 years, female gender, and receiving
      psychotropic therapy. Inadequate control may partly account for AEs attributed by
      patients to asthma therapy. Improving patients' education may help to improve
      acceptability of asthma therapy.

PMID- 17495877
TI  - Zebrafish: an emerging model system for human disease and drug discovery.
AB  - In vivo studies represent an essential step in drug development and currently
      rely largely on mice, yet limitations of mammalian models motivated the search
      for complementary vertebrate model systems. This review focuses on zebrafish,
      Danio rerio, as a facile model system to study human disease and drug responses.
      Zebrafish are particularly suited for this purpose because they represent a
      vertebrate species, their genome is sequenced, and a large number of
      synchronously developing, transparent embryos can be produced. Zebrafish embryos
      are permeable to drugs and can easily be manipulated using well-established
      genetic and molecular approaches. Here, we summarize recent work on drug
      discovery and toxicity in zebrafish embryos. In addition, we provide a synopsis
      of current efforts to establish disease models in zebrafish focusing on
      neoplasia. The results of these studies highlight the potential of zebrafish as a
      viable addition to established animal models by offering medium and, potentially,
      high throughput capabilities.

PMID- 17495878
TI  - Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper
      methysticum), inhibits human CYP3A activity in vivo.
AB  - The effects of goldenseal (Hydrastis canadensis) and kava kava (Piper
      methysticum) supplementation on human CYP3A activity were evaluated using
      midazolam (MDZ) as a phenotypic probe. Sixteen healthy volunteers were randomly
      assigned to receive either goldenseal or kava kava for 14 days. Each
      supplementation phase was followed by a 30-day washout period. MDZ (8 mg, per os)
      was administered before and after each phase, and pharmacokinetic parameters were
      determined using standard non-compartmental methods. Comparisons of pre- and post
      supplementation MDZ pharmacokinetic parameters revealed significant inhibition of
      CYP3A by goldenseal (AUC(0-infinity), 107.9+/-43.3 vs 175.3+/-74.8 ng x h/ml;
      Cl/F/kg, 1.26+/-0.59 vs 0.81+/-0.45 l/h/kg; T(1/2), 2.01+/-0.42 vs 3.15+/-1.12 h;
      Cmax, 50.6+/-26.9 vs 71.2+/-50.5 ng/ml). MDZ disposition was not affected by kava
      kava supplementation. These findings suggest that significant herb-drug
      interactions may result from the concomitant ingestion of goldenseal and CYP3A
      substrates.

PMID- 17495880
TI  - CYP3A5 and CYP3A4 but not MDR1 single-nucleotide polymorphisms determine long
      term tacrolimus disposition and drug-related nephrotoxicity in renal recipients.
AB  - The impact of CYP3A and MDR1 gene single-nucleotide polymorphisms on long-term
      tacrolimus disposition and drug-related toxicity has not been assessed. A study
      was performed in 95 genotyped recipients by measuring (12 and 4 h) concentration
      time curves on day 7; 3, 6 months; 1, 2, 3, 4, and 5 years after transplantation.
      In contrast to recipients carrying the CYP3A4*1/CYP3A5*1 or CYP3A4*1B/CYP3A5*1
      genotypes, dose-corrected tacrolimus exposure almost doubled over 5 years in
      patients with the CYP3A4*1/ CYP3A5*3 genotype (AUC(0-12 h): from 41.7+/-18.7 to
      80+/-39.2 ng h/ml/mg; P<0.05), whereas apparent oral steady-state clearance and
      dose requirements significantly decreased accordingly. The CYP3A4*1/CYP3A5*1 and
      CYP3A4*1B/CYP3A5*1 genotypes were significantly more frequently associated with
      the development of biopsy-proven tacrolimus-related nephrotoxicity than the
      CYP3A4*1/ CYP3A5*3 genotype (37.5 vs 11.2%; P=0.03 and 42.8 vs 11.2%; P=0.02).
      The lack of a time-related increase in dose-corrected tacrolimus exposure
      observed with the CYP3A4*1/CYP3A5*1 and CYP3A4*1B/CYP3A5*1 genotypes is
      associated with tacrolimus-related nephrotoxicity, possibly as a result of higher
      concentrations of toxic metabolites.

PMID- 17495879
TI  - Cyclooxygenase polymorphisms and risk of cardiovascular events: the
      Atherosclerosis Risk in Communities (ARIC) study.
AB  - Cyclooxygenase-derived prostaglandins modulate cardiovascular disease risk. We
      genotyped 2212 Atherosclerosis Risk in Communities study participants (1,023
      incident coronary heart disease (CHD) cases; 270 incident ischemic stroke cases;
      919 non-cases) with available DNA for polymorphisms in PTGS1 and PTGS2. Using a
      case-cohort design, associations between genotype and CHD or stroke risk were
      evaluated using proportional hazards regression. In Caucasians, the reduced
      function PTGS1 -1006A variant allele was significantly more common among stroke
      cases compared to non-cases (18.2 versus 10.6%, P=0.027). In African Americans,
      the reduced function PTGS2 -765C variant allele was significantly more common in
      stroke cases (61.4 versus 49.4%, P=0.032). No significant relationships with CHD
      risk were observed. However, aspirin utilization appeared to modify the
      relationship between the PTGS2 G-765C polymorphism and CHD risk (interaction
      P=0.072). These findings suggest that genetic variation in PTGS1 and PTGS2 may be
      important risk factors for the development of cardiovascular disease events.
      Confirmation in independent populations is necessary.

PMID- 17495881
TI  - Imatinib disposition and ABCB1 (MDR1, P-glycoprotein) genotype.
AB  - The aim of this study was to explore the impact of individual variation in drug
      elimination on imatinib disposition. Twenty-two patients with gastrointestinal
      stromal tumor or chronic myeloid leukemia initially received imatinib 600 mg
      daily with dosage subsequently toxicity adjusted. Pharmacokinetic parameters on
      day 1 and at steady-state were compared with elimination phenotype and single
      nucleotide polymorphisms of CYP3A5 and ABCB1. A fivefold variation in estimated
      imatinib clearance (CL/F) was present on day 1 and mean CL/F had fallen by 26% at
      steady state. This reduction in imatinib CL/F was associated with ABCB1 genotype,
      being least apparent in thymidine homozygotes at the 1236T>C, 2677G>T/A and
      3435C>T loci. Toxicity-related dose reduction also tended to be less common in
      these individuals. ABCB1 genotype was associated with steady-state CL/F due to an
      apparent genotype-specific influence of imatinib on elimination. Further
      evaluation of ABCB1 genotype and imatinib dosage is warranted.

PMID- 17495885
TI  - Starting at the top.

PMID- 17495886
TI  - A clear direction.

PMID- 17495887
TI  - Under the microscope.

PMID- 17495890
TI  - A clash of cosmologies.

PMID- 17495891
TI  - Snapshot: Ghosts of destruction.

PMID- 17495889
TI  - Climate panel offers grounds for optimism.

PMID- 17495893
TI  - Seven-year grant offers immune tolerance a boost.

PMID- 17495894
TI  - Wind farms' deadly reputation hard to shift.

PMID- 17495895
TI  - Microbe meeting promotes habitat conservation.

PMID- 17495897
TI  - Misspent energy.

PMID- 17495898
TI  - Cheap at any price?

PMID- 17495899
TI  - Climate change: is this what it takes to save the world?

PMID- 17495900
TI  - The good, the bad and the ugly.

PMID- 17495901
TI  - Chemistry: teetering on the edge.

PMID- 17495902
TI  - Codes must be updated so that names are known to all.

PMID- 17495903
TI  - Human reference sequence makes sense of names.

PMID- 17495904
TI  - Structured digital abstract makes text mining easy.

PMID- 17495905
TI  - A handful of carbon.

PMID- 17495910
TI  - Kinds of minds.

PMID- 17495911
TI  - Organic chemistry: radical catalysis.

PMID- 17495912
TI  - Developmental biology: a chordate with a difference.

PMID- 17495914
TI  - Extrasolar planets: remote climes.

PMID- 17495916
TI  - Condensed-matter physics: let's twist again.

PMID- 17495915
TI  - Biochemistry: the big catch.

PMID- 17495917
TI  - Obituary: Ransom Aldrich Myers (1952-2007).

PMID- 17495918
TI  - Completing the map of human genetic variation.

PMID- 17495920
TI  - A map of the day-night contrast of the extrasolar planet HD 189733b.
AB  - 'Hot Jupiter' extrasolar planets are expected to be tidally locked because they
      are close (<0.05 astronomical units, where 1 au is the average Sun-Earth
      distance) to their parent stars, resulting in permanent daysides and nightsides.
      By observing systems where the planet and star periodically eclipse each other,
      several groups have been able to estimate the temperatures of the daysides of
      these planets. A key question is whether the atmosphere is able to transport the
      energy incident upon the dayside to the nightside, which will determine the
      temperature at different points on the planet's surface. Here we report
      observations of HD 189733, the closest of these eclipsing planetary systems, over
      half an orbital period, from which we can construct a 'map' of the distribution
      of temperatures. We detected the increase in brightness as the dayside of the
      planet rotated into view. We estimate a minimum brightness temperature of 973 +/-
      33 K and a maximum brightness temperature of 1,212 +/- 11 K at a wavelength of 8
      mum, indicating that energy from the irradiated dayside is efficiently
      redistributed throughout the atmosphere, in contrast to a recent claim for
      another hot Jupiter. Our data indicate that the peak hemisphere-integrated
      brightness occurs 16 +/- 6 degrees before opposition, corresponding to a hotspot
      shifted east of the substellar point. The secondary eclipse (when the planet
      moves behind the star) occurs 120 +/- 24 s later than predicted, which may
      indicate a slightly eccentric orbit.

PMID- 17495919
TI  - Genome of the marsupial Monodelphis domestica reveals innovation in non-coding
      sequences.
AB  - We report a high-quality draft of the genome sequence of the grey, short-tailed
      opossum (Monodelphis domestica). As the first metatherian ('marsupial') species
      to be sequenced, the opossum provides a unique perspective on the organization
      and evolution of mammalian genomes. Distinctive features of the opossum
      chromosomes provide support for recent theories about genome evolution and
      function, including a strong influence of biased gene conversion on nucleotide
      sequence composition, and a relationship between chromosomal characteristics and
      X chromosome inactivation. Comparison of opossum and eutherian genomes also
      reveals a sharp difference in evolutionary innovation between protein-coding and
      non-coding functional elements. True innovation in protein-coding genes seems to
      be relatively rare, with lineage-specific differences being largely due to
      diversification and rapid turnover in gene families involved in environmental
      interactions. In contrast, about 20% of eutherian conserved non-coding elements
      (CNEs) are recent inventions that postdate the divergence of Eutheria and
      Metatheria. A substantial proportion of these eutherian-specific CNEs arose from
      sequence inserted by transposable elements, pointing to transposons as a major
      creative force in the evolution of mammalian gene regulation.

PMID- 17495921
TI  - Superconductivity in lithium below 0.4 millikelvin at ambient pressure.
AB  - Elements in the alkali metal series are regarded as unlikely superconductors
      because of their monovalent character. A superconducting transition temperature
      as high as 20 K, recently found in compressed lithium (the lightest alkali
      element), probably arises from pressure-induced changes in the conduction
      electron band structure. Superconductivity at ambient pressure in lithium has
      hitherto remained unresolved, both theoretically and experimentally. Here we
      demonstrate that lithium is a superconductor at ambient pressure with a
      transition temperature of 0.4 mK. As lithium has a particularly simple conduction
      electron system, it represents an important case for any attempts to classify
      superconductors and transition temperatures, especially to determine if any non
      magnetic configuration can exclude superconductivity down to zero temperature.
      Furthermore, the combination of extremely weak superconductivity and relatively
      strong nuclear magnetism in lithium would clearly lead to mutual competition
      between these two ordering phenomena under suitably prepared conditions.

PMID- 17495922
TI  - Chiral magnetic order at surfaces driven by inversion asymmetry.
AB  - Chirality is a fascinating phenomenon that can manifest itself in subtle ways,
      for example in biochemistry (in the observed single-handedness of biomolecules)
      and in particle physics (in the charge-parity violation of electroweak
      interactions). In condensed matter, magnetic materials can also display single
      handed, or homochiral, spin structures. This may be caused by the Dzyaloshinskii
      Moriya interaction, which arises from spin-orbit scattering of electrons in an
      inversion-asymmetric crystal field. This effect is typically irrelevant in bulk
      metals as their crystals are inversion symmetric. However, low-dimensional
      systems lack structural inversion symmetry, so that homochiral spin structures
      may occur. Here we report the observation of magnetic order of a specific
      chirality in a single atomic layer of manganese on a tungsten (110) substrate.
      Spin-polarized scanning tunnelling microscopy reveals that adjacent spins are not
      perfectly antiferromagnetic but slightly canted, resulting in a spin spiral
      structure with a period of about 12 nm. We show by quantitative theory that this
      chiral order is caused by the Dzyaloshinskii-Moriya interaction and leads to a
      left-rotating spin cycloid. Our findings confirm the significance of this
      interaction for magnets in reduced dimensions. Chirality in nanoscale magnets may
      play a crucial role in spintronic devices, where the spin rather than the charge
      of an electron is used for data transmission and manipulation. For instance, a
      spin-polarized current flowing through chiral magnetic structures will exert a
      spin-torque on the magnetic structure, causing a variety of excitations or
      manipulations of the magnetization and giving rise to microwave emission,
      magnetization switching, or magnetic motors.

PMID- 17495923
TI  - Short-circuiting of the overturning circulation in the Antarctic Circumpolar
      Current.
AB  - The oceanic overturning circulation has a central role in the Earth's climate
      system and in biogeochemical cycling, as it transports heat, carbon and nutrients
      around the globe and regulates their storage in the deep ocean. Mixing processes
      in the Antarctic Circumpolar Current are key to this circulation, because they
      control the rate at which water sinking at high latitudes returns to the surface
      in the Southern Ocean. Yet estimates of the rates of these processes and of the
      upwelling that they induce are poorly constrained by observations. Here we take
      advantage of a natural tracer-release experiment-an injection of mantle helium
      from hydrothermal vents into the Circumpolar Current near Drake Passage-to
      measure the rates of mixing and upwelling in the current's intermediate layers
      over a sector that spans nearly one-tenth of its circumpolar path. Dispersion of
      the tracer reveals rapid upwelling along density surfaces and intense mixing
      across density surfaces, both occurring at rates that are an order of magnitude
      greater than rates implicit in models of the average Southern Ocean overturning.
      These findings support the view that deep-water pathways along and across density
      surfaces intensify and intertwine as the Antarctic Circumpolar Current flows over
      complex ocean-floor topography, giving rise to a short circuit of the overturning
      circulation in these regions.

PMID- 17495924
TI  - The depth distribution of azimuthal anisotropy in the continental upper mantle.
AB  - The most likely cause of seismic anisotropy in the Earth's upper mantle is the
      lattice preferred orientation of anisotropic minerals such as olivine. Its
      presence reflects dynamic processes related to formation of the lithosphere as
      well as to present-day tectonic motions. A powerful tool for detecting and
      characterizing upper-mantle anisotropy is the analysis of shear-wave splitting
      measurements. Because of the poor vertical resolution afforded by this type of
      data, however, it has remained controversial whether the splitting has a
      lithospheric origin that is 'frozen-in' at the time of formation of the craton,
      or whether the anisotropy originates primarily in the asthenosphere, and is
      induced by shear owing to present-day absolute plate motions. In addition,
      predictions from surface-wave-derived models are largely incompatible with shear
      wave splitting observations. Here we show that this disagreement can be resolved
      by simultaneously inverting surface waveforms and shear-wave splitting data. We
      present evidence for the presence of two layers of anisotropy with different fast
      axis orientations in the cratonic part of the North American upper mantle. At
      asthenospheric depths (200-400 km) the fast axis is sub-parallel to the absolute
      plate motion, confirming the presence of shear related to current tectonic
      processes, whereas in the lithosphere (80-200 km), the orientation is
      significantly more northerly. In the western, tectonically active, part of North
      America, the fast-axis direction is consistent with the absolute plate motion
      throughout the depth range considered, in agreement with a much thinner
      lithosphere.

PMID- 17495925
TI  - Sexual dimorphism and adaptive radiation in Anolis lizards.
AB  - Sexual dimorphism is widespread and substantial throughout the animal world. It
      is surprising, then, that such a pervasive source of biological diversity has not
      been integrated into studies of adaptive radiation, despite extensive and growing
      attention to both phenomena. Rather, most studies of adaptive radiation either
      group individuals without regard to sex or focus solely on one sex. Here we show
      that sexual differences contribute substantially to the ecomorphological
      diversity produced by the adaptive radiations of West Indian Anolis lizards:
      within anole species, males and females occupy mostly non-overlapping parts of
      morphological space; the overall extent of sexual variation is large relative to
      interspecific variation; and the degree of variation depends on ecological type.
      Thus, when sexual dimorphism in ecologically relevant traits is substantial,
      ignoring its contribution may significantly underestimate the adaptive component
      of evolutionary radiation. Conversely, if sexual dimorphism and interspecific
      divergence are alternative means of ecological diversification, then the degree
      of sexual dimorphism may be negatively related to the extent of adaptive
      radiation.

PMID- 17495926
TI  - Maintaining a behaviour polymorphism by frequency-dependent selection on a single
      gene.
AB  - Accounting for the abundance of genetic variation in the face of natural
      selection remains a central problem of evolutionary biology. Genetic
      polymorphisms are constantly arising through mutation, and although most are
      promptly eliminated, polymorphisms in functionally important traits are common.
      One mechanism that can maintain polymorphisms is negative frequency-dependent
      selection on alternative alleles, whereby the fitness of each decreases as its
      frequency increases. Examples of frequency-dependent selection are rare,
      especially when attempting to describe the genetic basis of the phenotype under
      selection. Here we show frequency-dependent selection in a well-known natural
      genetic polymorphism affecting fruitfly foraging behaviour. When raised in low
      nutrient conditions, both of the naturally occurring alleles of the foraging gene
      (for(s) and for(R)) have their highest fitness when rare-the hallmark of negative
      frequency-dependent selection. This effect disappears at higher resources levels,
      demonstrating the role of larval competition. We are able to confirm the
      involvement of the foraging gene by showing that a sitter-like mutant allele on a
      rover background has similar frequency-dependent fitness as the natural sitter
      allele. Our study represents a clear demonstration of frequency-dependent
      selection, and we are able to attribute this effect to a single, naturally
      polymorphic gene known to affect behaviour.

PMID- 17495927
TI  - The human RNA kinase hClp1 is active on 3' transfer RNA exons and short
      interfering RNAs.
AB  - RNA interference allows the analysis of gene function by introducing synthetic,
      short interfering RNAs (siRNAs) into cells. In contrast to siRNA and microRNA
      duplexes generated endogenously by the RNaseIII endonuclease Dicer, synthetic
      siRNAs display a 5' OH group. However, to become incorporated into the RNA
      induced silencing complex (RISC) and mediate target RNA cleavage, the guide
      strand of an siRNA needs to display a phosphate group at the 5' end. The identity
      of the responsible kinase has so far remained elusive. Monitoring siRNA
      phosphorylation, we applied a chromatographic approach that resulted in the
      identification of the protein hClp1 (human Clp1), a known component of both
      transfer RNA splicing and messenger RNA 3'-end formation machineries. Here we
      report that the kinase hClp1 phosphorylates and licenses synthetic siRNAs to
      become assembled into RISC for subsequent target RNA cleavage. More importantly,
      we reveal the physiological role of hClp1 as the RNA kinase that phosphorylates
      the 5' end of the 3' exon during human tRNA splicing, allowing the subsequent
      ligation of both exon halves by an unknown tRNA ligase. The investigation of this
      novel enzymatic activity of hClp1 in the context of mRNA 3'-end formation, where
      no RNA phosphorylation event has hitherto been predicted, remains a challenge for
      the future.

PMID- 17495928
TI  - The hottest planet.
AB  - Of the over 200 known extrasolar planets, just 14 pass in front of and behind
      their parent stars as seen from Earth. This fortuitous geometry allows direct
      determination of many planetary properties. Previous reports of planetary thermal
      emission give fluxes that are roughly consistent with predictions based on
      thermal equilibrium with the planets' received radiation, assuming a Bond albedo
      of approximately 0.3. Here we report direct detection of thermal emission from
      the smallest known transiting planet, HD 149026b, that indicates a brightness
      temperature (an expression of flux) of 2,300 +/- 200 K at 8 microm. The planet's
      predicted temperature for uniform, spherical, blackbody emission and zero albedo
      (unprecedented for planets) is 1,741 K. As models with non-zero albedo are
      cooler, this essentially eliminates uniform blackbody models, and may also
      require an albedo lower than any measured for a planet, very strong 8 microm
      emission, strong temporal variability, or a heat source other than stellar
      radiation. On the other hand, an instantaneous re-emission blackbody model, in
      which each patch of surface area instantly re-emits all received light, matches
      the data. This planet is known to be enriched in heavy elements, which may give
      rise to novel atmospheric properties yet to be investigated.

PMID- 17495930
TI  - Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine
      phosphatases.
AB  - Reactive oxygen species trigger cellular responses by activation of stress
      responsive mitogen-activated protein kinase (MAPK) signalling pathways. Reversal
      of MAPK activation requires the transcriptional induction of specialized cysteine
      based phosphatases that mediate MAPK dephosphorylation. Paradoxically, oxidative
      stresses generally inactivate cysteine-based phosphatases by thiol modification
      and thus could lead to sustained or uncontrolled MAPK activation. Here we
      describe how the stress-inducible MAPK phosphatase, Sdp1, presents an unusual
      solution to this apparent paradox by acquiring enhanced catalytic activity under
      oxidative conditions. Structural and biochemical evidence reveals that Sdp1
      employs an intramolecular disulphide bridge and an invariant histidine side chain
      to selectively recognize a tyrosine-phosphorylated MAPK substrate. Optimal
      activity critically requires the disulphide bridge, and thus, to the best of our
      knowledge, Sdp1 is the first example of a cysteine-dependent phosphatase that
      couples oxidative stress with substrate recognition. We show that Sdp1, and its
      paralogue Msg5, have similar properties and belong to a new group of phosphatases
      unique to yeast and fungal taxa.

PMID- 17495931
TI  - Experimental and theoretical study of mitotic spindle orientation.
AB  - The architecture and adhesiveness of a cell microenvironment is a critical factor
      for the regulation of spindle orientation in vivo. Using a combination of theory
      and experiments, we have investigated spindle orientation in HeLa (human) cells.
      Here we show that spindle orientation can be understood as the result of the
      action of cortical force generators, which interact with spindle microtubules and
      are activated by cortical cues. We develop a simple physical description of this
      spindle mechanics, which allows us to calculate angular profiles of the torque
      acting on the spindle, as well as the angular distribution of spindle
      orientations. Our model accounts for the preferred spindle orientation and the
      shape of the full angular distribution of spindle orientations observed in a
      large variety of different cellular microenvironment geometries. It also
      correctly describes asymmetric spindle orientations, which are observed for
      certain distributions of cortical cues. We conclude that, on the basis of a few
      simple assumptions, we can provide a quantitative description of the spindle
      orientation of adherent cells.

PMID- 17495929
TI  - Prion recognition elements govern nucleation, strain specificity and species
      barriers.
AB  - Prions are proteins that can switch to self-perpetuating, infectious
      conformations. The abilities of prions to replicate, form structurally distinct
      strains, and establish and overcome transmission barriers between species are
      poorly understood. We exploit surface-bound peptides to overcome complexities of
      investigating such problems in solution. For the yeast prion Sup35, we find that
      the switch to the prion state is controlled with exquisite specificity by small
      elements of primary sequence. Strikingly, these same sequence elements govern the
      formation of distinct self-perpetuating conformations (prion strains) and
      determine species-specific seeding activities. A Sup35 chimaera that traverses
      the transmission barrier between two yeast species possesses the critical
      sequence elements from both. Using this chimaera, we show that the influence of
      environment and mutations on the formation of species-specific strains is driven
      by selective recognition of either sequence element. Thus, critical aspects of
      prion conversion are enciphered by subtle differences between small, highly
      specific recognition elements.

PMID- 17495932
TI  - Disulphide-isomerase-enabled shedding of tumour-associated NKG2D ligands.
AB  - Tumour-associated ligands of the activating NKG2D (natural killer group 2, member
      D; also called KLRK1) receptor-which are induced by genotoxic or cellular stress
      trigger activation of natural killer cells and co-stimulation of effector T
      cells, and may thus promote resistance to cancer. However, many progressing
      tumours in humans counter this anti-tumour activity by shedding the soluble major
      histocompatibility complex class-I-related ligand MICA, which induces
      internalization and degradation of NKG2D and stimulates population expansions of
      normally rare NKG2D+CD4+ T cells with negative regulatory functions. Here we show
      that on the surface of tumour cells, MICA associates with endoplasmic reticulum
      protein 5 (ERp5; also called PDIA6 or P5), which, similar to protein disulphide
      isomerase, usually assists in the folding of nascent proteins inside cells.
      Pharmacological inhibition of thioreductase activity and ERp5 gene silencing
      revealed that cell-surface ERp5 function is required for MICA shedding. ERp5 and
      membrane-anchored MICA form transitory mixed disulphide complexes from which
      soluble MICA is released after proteolytic cleavage near the cell membrane.
      Reduction of the seemingly inaccessible disulphide bond in the membrane-proximal
      alpha3 domain of MICA must involve a large conformational change that enables
      proteolytic cleavage. These results uncover a molecular mechanism whereby domain
      specific deconstruction regulates MICA protein shedding, thereby promoting tumour
      immune evasion, and identify surface ERp5 as a strategic target for therapeutic
      intervention.

PMID- 17495934
TI  - Placental ischemia and soluble fms-like tyrosine kinase 1: cause or consequence
      of preeclampsia?
AB  - Elevated circulating soluble fms-like tyrosine kinase 1 (sFLT-1) is associated
      with the development of the clinical signs and symptoms of preeclampsia.
      Placental ischemia has been suggested as one of the etiological factors that
      mediate increased sFLT-1 production in patients with preeclampsia, but definitive
      evidence for this hypothesis was lacking. Makris et al. demonstrate that inducing
      placental ischemia in primates is sufficient to induce sFLT-1 upregulation and
      the clinical signs and symptoms of preeclampsia.

PMID- 17495935
TI  - Evidence mounts for a role of the kidney in lipoprotein(a) catabolism.
AB  - Numerous studies have suggested a role of the kidney in lipoprotein(a) (Lp(a))
      catabolism, but direct evidence is still lacking. Frischmann et al. demonstrate
      that the marked elevation of Lp(a) observed in hemodialysis patients results from
      a decrease in Lp(a) clearance rather than an increase in Lp(a) production,
      consistent with the notion that the kidney degrades Lp(a). More studies are
      needed to prove the biological relevance.

PMID- 17495936
TI  - Pediatric acute kidney injury: the use of the RIFLE criteria.
AB  - Outcome in pediatric acute kidney injury (AKI) is in part related to diagnosis
      and intervention. Standard markers of severity of illness do not identify AKI.
      Modified RIFLE criteria are shown to identify patients who develop AKI,
      potentially allowing for early intervention.

PMID- 17495938
TI  - Risk factors affecting the incidence of chronic kidney disease.

PMID- 17495941
TI  - Reduced kidney function in living kidney donors.

PMID- 17495942
TI  - Glycosylated hemoglobin, glycemic control, and mortality in hemodialyzed diabetic
      patients.

PMID- 17495944
TI  - Nephrology image. A cyst in a stone?

PMID- 17495945
TI  - Nephrology image. Hand-digit gangrene in a hemodialysis patient following
      brachioaxillary bridge graft creation.

PMID- 17495946
TI  - HSV-1 amplicon-mediated post-transcriptional inhibition of Rad51 sensitizes human
      glioma cells to ionizing radiation.
AB  - Standard treatment for glioblastoma multiforme and other brain tumors consists of
      surgical resection followed by combined radio-/chemotherapy. However, radiation
      resistance of tumor cells limits the success of this treatment, and the tumors
      invariably recur. Therefore, the selective inhibition of molecular mediators of
      radiation resistance may provide therapeutic benefit to the patient. One of these
      targets is the Rad51 protein, which is a key component of the homologous
      recombinational repair of DNA double-strand breaks. Here, we investigated whether
      post-transcriptional silencing of Rad51 by herpes simplex virus-type 1 (HSV-1)
      amplicon vector-mediated short interfering RNA expression can enhance the
      antitumor effect of radiation therapy. We demonstrate that these vectors
      specifically and efficiently inhibited the radiation-induced recruitment of Rad51
      into nuclear foci in human glioma cells. The combination of vector-mediated
      silencing of Rad51 expression and treatment with ionizing radiation resulted in a
      pronounced reduction of the survival of human glioma cells in culture. In athymyc
      mice, a single intratumoral injection of Rad51-specific HSV-1 amplicon vector
      followed by a single radiation treatment resulted in a significant decrease in
      tumor size. In control animals, including mice that received an intratumoral
      injection of Rad51-specific amplicon vector but no radiation treatment, the tumor
      sizes increased.

PMID- 17495947
TI  - Synergistic antileukemia effect of combinational gene therapy using murine beta
      defensin 2 and IL-18 in L1210 murine leukemia model.
AB  - Murine beta-defensin 2 (MBD2) is not only chemotactic for immature dendritic
      cells but also activates them by Toll-like receptor 4. We have previously
      demonstrated that vaccine with MBD2 elicited potent antileukemia responses in the
      L1210 murine model. Interleukin-18 (IL-18) is an essential cytokine for the
      generation of Th1 response and natural killer cells and cytotoxic T lymphocytes
      (CTL) activation. As MBD2 and IL-18 appear to function on different components
      required by an effective antitumor immune response including both innate and
      adaptive immunity, we investigated whether combinatorial delivery of MBD2 and IL
      18 transduced L1210 cells could elicit synergistic antileukemia effects. First,
      we constructed a single plasmid vector carrying both pro-IL-18 and IL-1beta
      converting enzyme (ICE) genes, and found that transfection of this vector into
      L1210 cells resulted in efficient secretion of bioactive IL-18. Combinatorial
      delivery of MBD2 and pro-IL-18-ICE modified L1210 cells conferred a superior
      inhibition of leukemogenicity over either L1210-MBD2 or L1210-pro-IL-18-ICE
      alone; moreover, the survived mice developed long-lasting protective immunity as
      determined by rechallenge experiments. This combined vaccine also elicited the
      most marked therapeutic effect, CTL activity and interferon-gamma production.
      These results suggest that the combination of MBD2 and IL-18 induces more
      effective antileukemia activity and provides a promising strategy for cancer
      therapy.

PMID- 17495948
TI  - Mutation of Escherichia coli cytosine deaminase significantly enhances molecular
      chemotherapy of human glioma.
AB  - Combined treatment using adenoviral (Ad)-directed enzyme/prodrug therapy and
      radiation therapy has the potential to become a powerful method of cancer
      therapy. We have developed an Ad vector encoding a mutant bacterial cytosine
      deaminase (bCD) gene (AdbCD-D314A), which has a higher affinity for cytosine than
      wild-type bCD (bCDwt). The purpose of this study was to evaluate cytotoxicity in
      vitro and therapeutic efficacy in vivo of the combination of AdbCD-D314A with the
      prodrug 5-fluorocytosine (5-FC) and ionizing radiation against human glioma. The
      present study demonstrates that AdbCD-D314A infection resulted in increased 5-FC
      mediated cell killing, compared with AdbCDwt. Furthermore, a significant increase
      in cytotoxicity following AdbCD-D314A and radiation treatment of glioma cells in
      vitro was demonstrated as compared to AdbCDwt. Animal studies showed significant
      inhibition of subcutaneous or intracranial tumor growth of D54MG glioma
      xenografts by the combination of AdbCD-D314A/5-FC with ionizing radiation as
      compared with either agent alone, and with AdbCDwt/5-FC plus radiation. The
      results suggest that the combination of AdbCD-D314A/5-FC with radiation produces
      markedly increased cytotoxic effects in cancer cells in vitro and in vivo. These
      data indicate that combined treatment with this novel mutant enzyme/prodrug
      therapy and radiotherapy provides a promising approach for cancer therapy.

PMID- 17495949
TI  - Urinary albumin excretion, endothelial dysfunction and cardiovascular risk: study
      in Bartter's/Gitelman's syndromes and relevance for hypertension.

PMID- 17495950
TI  - Insertion/deletion gene polymorphism of the angiotensin-converting enzyme and
      blood pressure changes in older adults. The Rotterdam study.
AB  - The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme
      (ACE) gene may be involved in determining blood pressure changes. The aim of the
      present study was to assess the relationship between the ACE I/D gene and the
      change of blood pressure levels during follow-up. We calculated the difference
      between mean levels of SBP, DBP and PP obtained during the two observations as
      follows: BP mean levels obtained at third phase minus the BP mean levels at
      baseline and subsequently we investigated the association of the ACE I/D
      polymorphism and the mean changes of SBP, DBP and PP levels. The study was
      conducted within the Rotterdam Study, a population-based cohort study including
      subjects aged 55 years and older. Information on the II, ID and DD genotypes of
      the ACE gene and mean change of blood pressure levels were available in 3966
      subjects. In adjusted models, subjects with the D allele had higher mean changes
      of systolic and pulse pressure (PP) than subjects with the I allele. The mean
      changes of systolic blood pressure were 6.1 (4.7-7.5), 8.2 (7.5-9.3) and 7.4 (5.9
      8.5) mm Hg in subjects with the II, ID and DD genotype, respectively. The
      corresponding mean changes of PP through genotypes were 4.3 (3.3-5.4), 6.0 (5.3
      6.7) and 5.9 (4.9-6.9) mm Hg, respectively. No difference was found for mean
      change of diastolic blood pressure among genotypes. In conclusion, the results of
      this population-based study show that the ACE ID/DD genotypes are associated with
      increased mean changes of systolic and PP.

PMID- 17495951
TI  - Epigenetic control of the S100A6 (calcyclin) gene expression.
AB  - S100A6 (calcyclin) is a calcium-binding protein of cell-specific expression whose
      gene is clustered with other S100 genes within the epidermal differentiation
      complex, on human chromosome 1q21. Many S100 proteins, including S100A6, are
      expressed in human epidermis at various stages of differentiation and their
      expression is often deregulated in skin and epithelial cancers. To gain insight
      into the mechanism of regulation of S100A6 expression, we examined epigenetic
      marks, that is DNA methylation and histone modifications along the S100A6 gene.
      Sequencing of bisulfite-modified DNA within a 3,247 bp long genomic region
      encompassing the promoter/first exon CpG island, the coding sequence of the
      S100A6 gene and a downstream region showed that it is almost entirely methylation
      free in S100A6 expressing human epidermoid carcinoma (Hep-2) cells and
      lymphocytes and methylated in S100A6-negative embryonic epithelial (HEK293)
      cells. Chromatin immunoprecipitation revealed profound differences in the level
      of histone H3 acetylation and methylation and in the in vivo binding of upstream
      regulatory factor (USF), to the S100A6 gene promoter in S100A6-negative and 
      positive cells. These data demonstrate that cell-specific S100A6 expression is
      under control of epigenetic mechanisms.

PMID- 17495952
TI  - Patients with recessive dystrophic epidermolysis bullosa develop squamous-cell
      carcinoma regardless of type VII collagen expression.
AB  - Recent data suggest that individuals with recessive dystrophic epidermolysis
      bullosa (RDEB) only develop squamous-cell carcinoma (SCC) in the presence of the
      NC1 domain of type VII collagen. This conclusion was based on experimental work
      in which cryosections of SCCs from 10 people with RDEB all showed positive type
      VII collagen immunostaining and observations in a murine model of SCC development
      in which tumors only occurred using keratinocytes from RDEB subjects that
      expressed detectable levels of the NC1 domain of the type VII collagen protein.
      To assess whether the clinical interpretation was valid in another cohort of RDEB
      patients, we examined expression of type VII collagen in 17 SCC tumors excised
      from 11 patients. Indirect immunofluorescent staining of SCC cryosections and
      Western blotting of cultured keratinocyte lysates identified two RDEB individuals
      who did not express detectable levels of type VII collagen. Mutation analysis
      revealed that these two patients harbor compound heterozygous nonsense mutations
      within the region of the COL7A1 gene encoding the NC1 domain. These data suggest
      that individuals with RDEB can develop SCC regardless of type VII collagen
      expression and that additional factors have a role in explaining the high
      incidence of tumors complicating this genodermatosis.

PMID- 17495953
TI  - Cross-cultural inequivalence of dermatology-specific health-related quality of
      life instruments in psoriasis patients.
AB  - The dermatology life questionnaire index (DLQI) and the Skindex are the most
      commonly used dermatology-specific health-related quality of life (HRQOL)
      instruments. Although these tools are used in international surveys and clinical
      trials, the cross-cultural equivalence of their items has not been documented. We
      used differential item functioning (DIF), which is part of the Rasch model, to
      assess the impact of cultural background on the items of the DLQI and Skindex-29
      and-17. The data of the 450 psoriasis patients, who attended in- and outpatient
      dermatology centers, was collected retrospectively from five European and one US
      center. The DLQI and Skindex-29 scales did not fit the Rasch model (P<0.0008) and
      10/10 of the DLQI and 19/29 of the Skindex-29 items displayed significant DIF.
      Although the psychosocial scale of the Skindex-17 fitted the Rasch model, half or
      more of the items of the psychosocial (6/12) and the symptom scale (4/5) showed
      significant DIF across countries. These findings suggest that psoriasis patients
      from different countries respond differently to a substantial proportion of DLQI
      and Skindex items despite having the same level of underlying HRQOL impairment.
      Therefore, these instruments should not be used in their current form in
      international studies.

PMID- 17495954
TI  - Upregulation of hypoxia-inducible factors in normal and psoriatic skin.
AB  - Angiogenesis induced by vascular endothelial growth factor (VEGF) plays an
      important role in psoriasis. Hypoxic adaptation is conferred through hypoxia
      inducible transcription factors (HIFs). VEGF and its receptor Flt-1 are HIF
      target genes. Growth factors and inflammatory cytokines activate the
      phosphoinositol-3 kinase pathway, and via activated protein kinase B (phospho
      Akt) augment HIF activity. Here, we demonstrate that the major oxygen-dependent
      HIF isoforms are strongly upregulated in psoriatic skin: HIF-1alpha mainly in the
      epidermis, in an expression pattern similar to VEGF mRNA; HIF-2alpha in both the
      epidermis and in capillary endothelial cells of the dermis. In contrast, normal
      human skin shows low expression of HIF-alpha proteins, with the exception of hair
      follicles, and glands, which strongly express HIF-1alpha. In normal human skin,
      phospho-Akt appeared in the basal epidermal layer, in hair follicles, and in
      dermal glands. In contrast, in psoriasis, phospho-Akt expression was low in the
      epidermis, but markedly enhanced in the dermal capillaries and in surrounding
      interstitial/inflammatory cells. Our data suggest that hypoxia initiates a
      potentially self-perpetuating cycle involving HIF, VEGF, and Akt activation,
      which could drive physiologic growth of hair follicles and skin glands.
      Furthermore, such a cycle may exist in psoriasis in dermal capillaries and
      contribute to disease progression.

PMID- 17495955
TI  - CXCL13 and CCL21 are expressed in ectopic lymphoid follicles in cutaneous
      lymphoproliferative disorders.

PMID- 17495956
TI  - Galectin-1 knockdown increases sensitivity to temozolomide in a B16F10 mouse
      metastatic melanoma model.
AB  - The rapid increase in the incidence of malignant melanomas has not been
      associated with improved therapeutic options over the years. Indeed melanomas
      have proven resistant to apoptosis (type I programmed cell death (PCD)) and
      consequently to most chemotherapy and immunotherapy. It is believed that this
      resistance can be partly overcome by proautophagic drugs inducing type II
      (autophagy) PCD. Change at the genomic, transcriptional, and post-translational
      level of G-proteins and protein kinases, including Ras, plays an important role
      in the ability of melanomas to resist apoptosis. Ras transformation itself
      requires membrane anchorage and the overexpression of galectin-1 increases
      membrane-associated Ras. In this study, it has been found that decreasing
      galectin-1 expression in B16F10 mouse melanoma cells in vitro by means of an anti
      galectin-1 small interfering RNA approach does not modify their sensitivity to
      type I and type II PCD. However, it does induce heat shock protein 70-mediated
      lysosomal membrane permeabilization, a process associated with cathepsin B
      release into the cytosol, which in turn is believed to sensitize the cells to the
      proautophagic effects of temozolomide when grafted in vivo. Furthermore,
      temozolomide when compared to the proapoptotic drug cisplatin, significantly
      increased the survival times of mice in the B16F10 melanoma model.

PMID- 17495957
TI  - Blockade of death receptor-mediated pathways early in the signaling cascade
      coincides with distinct apoptosis resistance in cutaneous T-cell lymphoma cells.
AB  - Control of apoptosis via death ligands plays a basic role for lymphocyte
      homeostasis and lymphoma development. In this study, cutaneous T-cell lymphoma
      (CTCL) cell lines revealed pronounced resistance to death ligands as compared to
      cell lines of T-cell acute lymphoblastic leukemia (T-ALL). The proapoptotic
      activity of tumor necrosis factor (TNF)-alpha was blocked, sensitivity to TNF
      related apoptosis-inducing ligand was significantly reduced, and 1/4 CTCL cell
      lines was resistant to CD95 activation. In parallel, there was no activation of
      effector caspase-3 and initiator caspase-8 in nonresponsive CTCL cells, whereas
      caspase-10 was cleaved selectively in sensitive CTCL cells. No indication for a
      responsibility of typical downstream regulators of apoptosis was obtained, but
      loss of CD95 was found in 1/4, loss of TNF-R1 in 3/4, loss of caspase-10 in 2/4,
      loss of Bid in 1/4, and overexpression of cellular flice inhibitory protein was
      found in 4/4 CTCL cell lines. This clearly indicates an inhibition of apoptosis
      early in the extrinsic cascade, namely at the formation of the death-inducing
      signaling complex. Parallels with regard to expression of apoptosis regulators
      were seen in peripheral blood mononuclear cells and biopsies of CTCL patients.
      This study may indicate defects in apoptosis in CTCL and may help to guide CTCL
      therapy.

PMID- 17495958
TI  - Biphasic regulation of AP-1 subunits during human epidermal wound healing.
AB  - Cutaneous wound healing is a well-coordinated process that includes inflammation,
      proliferation, and differentiation. Activator protein 1 (AP-1) subunits have been
      implicated in the regulation of genes important for these processes and have been
      shown to be involved in wound healing. However, investigation of human healing
      and non-healing wounds in vivo and ex vivo, and the comparative analysis of
      several members of the Jun and Fos families are still missing. Here, we show that
      normal human epidermal wound healing is biphasic. In the first phase all AP-1
      subunits investigated, that is c-Jun, Jun B, Jun D, c-Fos, and Fos B are absent
      from the nuclei at the wound margins/leading edges. This downregulation coincides
      with that of the gap junction protein connexin 43. Later on, c-Jun, Jun B, Jun D,
      and c-Fos reappear in the nuclei of the leading edges in a time-dependent manner.
      In non-healing wounds, a more intensive staining of keratinocytes at the wound
      margins is often observed. Our findings suggest that coordinated down- and
      upregulation of the various AP-1 subunits in the course of epidermal wound
      healing is important for its undisturbed progress, putatively by influencing
      inflammation and cell-cell communication.

PMID- 17495959
TI  - Epidermal growth factor receptor pathway mitigates UVA-induced G2/M arrest in
      keratinocyte cells.
AB  - UVA irradiation contributes largely to photocarcinogenesis. In the process of
      keratinocyte transformation, the activation of EGFR by UV is now considered as a
      critical event. However, the mechanism that links the EGFR pathway and
      photocarcinogenesis is not totally understood. In this study, we report that the
      EGFR/Akt pathway mitigated G2/M arrest in human HaCaT keratinocytes and normal
      human keratinocytes treated with low doses of UVA irradiation. EGFR-mediated Akt
      activation resulted in increased level of checkpoint 1 kinase (Chk1) inhibitory
      phosphorylation (Ser280). In contrast, EGFR/Akt pathway inhibition resulted in
      the abrogation of Ser280 Chk1 phosphorylation, increased level of Chk1
      stimulatory phosphorylation (Ser345), and restoration of G2/M arrest. Altogether,
      these results suggest that, after UVA exposure, the EGFR/Akt pathway subverts the
      G2/M checkpoint. This effect may have serious implications in photocarcinogenesis
      by allowing damaged cells to transit through the cell cycle.

PMID- 17495960
TI  - A novel S115G mutation of CGI-58 in a Turkish patient with Dorfman-Chanarin
      syndrome.

PMID- 17495961
TI  - Dimethylfumarate specifically inhibits the mitogen and stress-activated kinases 1
      and 2 (MSK1/2): possible role for its anti-psoriatic effect.
AB  - The p38 mitogen-activated protein kinase (MAPK) signaling pathway, which
      regulates the activity of different transcriptions factors including NF-kappaB,
      is activated in lesional psoriatic skin. The purpose of this study was to
      investigate the effect of fumaric acid esters (FAEs) on the p38 MAPK and the
      downstream kinases mitogen- and stress-activated protein kinase (MSK)1 and 2 in
      cultured human keratinocytes. Cell cultures were incubated with dimethylfumarate
      (DMF), methylhydrogenfumarate (MHF), or fumaric acid (FA) and then stimulated
      with IL-1beta before kinase activation was determined by Western blotting. A
      significant inhibition of both MSK1 and 2 activations was seen after
      preincubation with DMF and stimulation with IL-1beta, whereas MHF and FA had no
      effect. In addition, DMF decreased phosphorylation of NF-kappaB/p65 (Ser276),
      which is known to be transactivated by MSK1. Furthermore, incubation with DMF
      before stimulation with IL-1beta resulted in a significant decrease in NF-kappaB
      binding to the IL-8 kappaB and the IL-20 kappaB-binding sites as well as a
      subsequent decrease in IL-8 and IL-20 mRNA expression. Our results suggest that
      DMF specifically inhibits MSK1 and 2 activations and subsequently inhibits NF
      kappaB-induced gene-transcriptions, which are believed to be important in the
      pathogenesis of psoriasis. These effects of DMF explain the anti-psoriatic effect
      of FAEs.

PMID- 17495962
TI  - CGRP, PACAP, and VIP modulate Langerhans cell function by inhibiting NF-kappaB
      activation.
AB  - The neuropeptides calcitonin gene-related peptide (CGRP), pituitary adenylate
      cyclase-activating polypeptide (PACAP), and vasoactive intestinal peptide (VIP)
      suppress Langerhans cell (LC) antigen presentation and modulate cytokine
      production. We have tested the hypothesis that these neuropeptides (NP) inhibit
      LC function by modulating activation of NF-kappaB. Lipopolysaccharide (LPS)
      activates NF-kappaB in both a LC-like cell line (XS52) and epidermal LC enriched
      to approximately 95% and this effect is inhibited by each of the NP. Furthermore,
      CGRP, PACAP, and VIP suppress phosphorylation of IkappaB kinase beta (P-IKKbeta),
      prevent degradation of the IkappaB alpha, and inhibit activation of NF-kappaB.
      Thus, these NP modulate LC function by reducing NF-kappaB activation. Bay 11
      7085, an inhibitor of IKK, reduced tumor necrosis factor-alpha (TNFalpha)
      production from LPS-stimulated XS52 cells and inhibited the ability of LC to
      present antigen to a T-cell clone in vitro. Each NP also inhibited LPS-induced
      secretion of TNFalpha by XS52 cells and LC enriched to approximately 95%
      homogeneity. We suggest that the inhibitory activities of CGRP, PACAP, and VIP on
      LC function are mediated, at least in part, by inhibition of P-IKKbeta, which
      prevents IkappaB alpha degradation and activation of NF-kappaB. Modulation of
      this signaling pathway may be useful for therapeutic modulation of immunity in
      the skin.

PMID- 17495963
TI  - Homo- and heterotypic cell contacts in malignant melanoma cells and desmoglein 2
      as a novel solitary surface glycoprotein.
AB  - During progression of melanomas, a crucial role has been attributed to
      alterations of cell-cell adhesions, specifically, to a "cadherin switch" from E-
      to N-cadherin (cad). We have examined the adhesion of melanoma cells to each
      other and to keratinocytes. When different human melanoma cell lines were studied
      by protein analysis and immunofluorescence microscopy, six of eight lines
      contained N-cad, three E-cad, and five P-cad, and some lines had more than one
      cad. Surprisingly, two N-cad-positive lines, MeWo and C32, also contained
      desmoglein 2 (Dsg2), a desmosomal cad previously not reported for melanomas,
      whereas other desmosome-specific proteins were absent. This finding was confirmed
      by reverse transcriptase-PCR, immunoprecipitation, and matrix-assisted laser
      desorption ionization-time of flight analyses. Double-label confocal and
      immunoelectron microscopy showed N-cad, alpha- and beta-catenin in plaque-bearing
      puncta adhaerentia, whereas Dsg2 was distributed rather diffusely over the cell
      surface. In cocultures with HaCaT keratinocytes Dsg2 was found in heterotypic
      cell contact regions. Correspondingly, immunohistochemistry revealed Dsg2 in five
      of 10 melanoma metastases. Together, we show that melanoma cell adhesions are
      more heterogeneous than expected and that certain cells devoid of desmosomes
      contain Dsg2 in a non-junction-restricted form. Future studies will have to
      clarify the diagnostic and prognostic significance of these different adhesion
      protein subtypes.

PMID- 17495964
TI  - Epigenetic control of MAGE gene expression by the KIT tyrosine kinase.
AB  - The Class I MAGE proteins include the MAGE-A, MAGE-B, and MAGE-C antigens, which
      are normally expressed only in male germ cells but may be aberrantly expressed in
      melanomas and other tumors. It is known that MAGE gene expression is
      epigenetically repressed by promoter region methylation in most cells but factors
      controlling MAGE gene promoter methylation have not been identified. Using
      transcript microarray analysis and immunoblotting we found that MAGE-A and MAGE-C
      mRNA and protein are selectively downregulated by pharmacologic inhibition of KIT
      in KIT-dependent mast cell lines. Methylation-specific polymerase chain reaction
      studies showed that the MAGE-A3 and MAGE-C2 gene promoter regions were de
      methylated in the presence of activated KIT but became methylated on inhibition
      of KIT, consistent with the downregulation of mRNA and protein. This is early
      evidence of a tyrosine kinase affecting MAGE gene promoter region methylation and
      expression, and represents early evidence of a tyrosine kinase in the epigenetic
      control of gene expression. MAGE proteins suppress apoptosis and promote tumor
      survival, and are novel targets for functional manipulation and immunotherapy.
      Understanding the factors controlling MAGE gene expression may allow more
      effective therapeutic strategies targeting MAGE antigens.

PMID- 17495965
TI  - DNA damage check points prevent leukemic transformation in myelodysplastic
      syndrome.

PMID- 17495966
TI  - Elevated mRNA transcripts of non-homologous end-joining genes in pediatric acute
      lymphoblastic leukemia.

PMID- 17495967
TI  - The dynamics of the B follicle: understanding the normal counterpart of B-cell
      derived malignancies.
AB  - The repertoire of B cells secreting antibodies with unique antigen-binding
      specificities is produced at two stages: a primary B-cell repertoire is formed in
      the bone marrow through immunoglobulin gene rearrangements, whereas a secondary B
      cell repertoire is generated in the peripheral lymphoid organs (spleen, lymph
      nodes and mucosa-associated lymphoid tissue) through somatic hypermutation and
      class-switch recombination upon antigen encounter. The latter events take place
      within highly specialized histological structures, designated B follicles, which
      are composed of distinct microanatomical compartments namely the follicle centre,
      lymphocytic corona and marginal zone. Each compartment comprises a particular
      subset of B cells, characterized by unique properties, thereby reflecting the
      complexity and variability in the spectrum of defence mechanisms against invading
      pathogens. The past years have spawned an avalanche of new data and information
      that encompasses both the structure and function of each compartment and its B
      cells. This review incorporates up-to-date information on peripheral B-cell
      differentiation into a challenging working model, thereby pointing to the
      structural and functional imprint of both the T-cell-dependent and T-cell
      independent immune response on the B follicle. As such, this article aims to form
      an excellent base for a better understanding of the normal counterpart of B-cell
      derived haematological malignancies (leukemias and lymphomas).

PMID- 17495968
TI  - Conventional cytogenetics of nodular lymphocyte-predominant Hodgkin's lymphoma.

PMID- 17495969
TI  - Arsenic trioxide and proteasome inhibitor bortezomib synergistically induce
      apoptosis in leukemic cells: the role of protein kinase Cdelta.
AB  - Arsenic trioxide (ATO) and proteasome inhibitor bortezomib have been successfully
      applied to treat acute promyelocytic leukemia (APL) and multiple myeloma (MM),
      respectively. Their synergistic effects with other anticancer drugs have been
      widely studied. Here, we investigated the potential synergy of bortezomib and ATO
      on Bcr-Abl(+) leukemic K562 cells. The results showed that cotreatment of
      bortezomib at 32 nM, a half concentration for growth arrest, and ATO at 1 microM,
      a dose with no significant cytotoxic effect, synergistically induced apoptosis in
      the cell line, followed by enhanced mitochondrial dysfunction, release of
      cytochrome c and apoptosis-inducing factor, caspase-3 cleavage and degradation of
      poly-adenosine diphosphate-ribose polymerase together with the decreased Bcr-Abl
      protein. These two drugs synergistically induced proteolytic activation of
      protein kinase Cdelta (PKCdelta) with enhanced activation of two mitogen
      activated protein kinases phospho-c-Jun NH(2)-terminal kinase and p38. The
      specific PKCdelta inhibitor rottlerin markedly decreased bortezomib plus ATO
      induced apoptosis, suggesting that PKCdelta plays an important role in bortezomib
      plus ATO-induced apoptosis. Moreover, apoptosis synergy of bortezomib and ATO
      could also be seen in some kinds of acute leukemic cell lines and primary cells.
      Totally, our results indicate that combined regimen of bortezomib and ATO might
      be a potential therapeutic remedy for the treatment of leukemia.

PMID- 17495970
TI  - Bortezomib significantly impairs the immunostimulatory capacity of human myeloid
      blood dendritic cells.
AB  - Bortezomib is a potent drug for the treatment of multiple myeloma. Its anti-tumor
      activity is mediated by proteasome inhibition leading to decreased cell
      proliferation and induction of apoptosis. However, an unimpaired proteasomal
      function plays a crucial role for the induction of anti-tumor immunity by
      dendritic cells (DCs), which are currently used for therapeutic vaccination
      against various tumors including myeloma. In the present study, we investigated
      the impact of bortezomib on the immunostimulatory capacity of 6-sulfo LacNAc
      (slan) DCs, which represent a major subset of human blood DCs. We demonstrated
      that this proteasome inhibitor efficiently impairs the spontaneous in vitro
      maturation of slanDCs and the release of tumor necrosis factor (TNF)-alpha as
      well as interleukin (IL)-12 upon lipopolysaccharide (LPS) stimulation. Functional
      data revealed that bortezomib profoundly inhibits slanDC-induced proliferation
      and differentiation of CD4(+) T cells. In addition, the capacity of slanDCs to
      promote interferon-gamma secretion and tumor-directed cytotoxicity of natural
      killer (NK) cells is markedly impaired by bortezomib. These results provide
      evidence that bortezomib significantly reduces the ability of native human blood
      DCs to regulate innate and adaptive anti-tumor immunity and may have implications
      for the design of therapeutic strategies combining DC vaccination and bortezomib
      treatment.

PMID- 17495971
TI  - Chronic myeloid leukemia--some topical issues.

PMID- 17495972
TI  - Treatment of steroid-resistant acute GVHD with OKT3 and high-dose steroids
      results in better disease control and lower incidence of infectious complications
      when compared to high-dose steroids alone: a randomized multicenter trial by the
      EBMT Chronic Leukemia Working Party.

PMID- 17495973
TI  - Comparison of a quantitative PCR method with FISH for the assessment of the four
      aneuploidies commonly evaluated in CLL patients.
AB  - Four chromosomal defects associated with outcome are commonly evaluated by
      fluorescent in situ hybridization (FISH) in chronic lymphocytic leukemia (CLL),
      namely deletions of the 13q13-q14, 11q22 and 17p13 regions and trisomy 12. In
      this study, we compared a quantitative PCR method--quantitative multiplex PCR of
      short fluorescent fragment (QMPSF)--with FISH for the detection of these acquired
      aneuploidies in a series of 110 patients with Binet stage A CLL. Genes located in
      the deleted or gained regions were selected as target genes and amplified using a
      method based on the simultaneous amplification of short fluorescent genomic
      fragments under quantitative conditions. A chromosomal imbalance involving one or
      several of the four loci was detected by either method in 72 patients (65%). A
      chromosome 13 deletion was present in 61 patients (54%), a 11q22 deletion in nine
      (8%), a trisomy 12 in nine and a 17p deletion in one. FISH and QMPSF results were
      identical for 103 out of 110 patients and discrepancies could be explained in
      most cases. This study demonstrates that a quantitative multiplex PCR represents
      a cost-effective method that could replace FISH in CLL patients. However,
      although QMPSF is perfectly adapted to the detection of primary defects, care
      should be taken when searching for clonal evolutions present in a small
      proportion of tumor cells.

PMID- 17495974
TI  - The HOXB4 homeoprotein improves ex vivo generation of functional human NK-cell
      progenitors.

PMID- 17495975
TI  - The novel tyrosine kinase inhibitor EXEL-0862 induces apoptosis in human FIP1L1
      PDGFR-alpha-expressing cells through caspase-3-mediated cleavage of Mcl-1.
AB  - The FIP1-like-1 (FIP1L1)-platelet-derived growth factor receptor-alpha (FIP1L1
      PDGFR-alpha) fusion kinase causes hypereosinophilic syndrome (HES) in a defined
      subset of patients. Imatinib mesylate is a potent inhibitor of ABL but also of
      PDGFR-alpha, and has been associated with durable hematologic responses in
      patients with HES. However, development of mutations in the tyrosine kinase
      domain may hamper the activity of tyrosine kinase inhibitors (TKIs), which
      suggests that novel agents are warranted to prevent or overcome resistance. We
      evaluated the efficacy of the novel TKI EXEL-0862 in FIP1L1-PDGFR-alpha
      expressing cell lines and in cells from a patient with HES harboring the FIP1L1
      PDGFR-alpha gene. EXEL-0862 inhibited the proliferation of EOL-1 and imatinib
      resistant T674I FIP1L1-PDGFR-alpha-expressing cells and resulted in potent
      inhibition of the phosphorylation of PDGFR-alpha and downstream proteins STAT3
      and Erk1/2, both in vitro and ex vivo. Moreover, EXEL-0862 induced apoptotic
      death in EOL-1 cells and imatinib-resistant T674I FIP1L1-PDGFR-alpha-expressing
      cells, and resulted in significant downregulation of the antiapoptotic protein
      Mcl-1 through a caspase-dependent mechanism. Our data establish EXEL-0862 as a
      solid candidate for the targeted treatment of patients with FIP1L1-PDGFR-alpha
      positive HES.

PMID- 17495976
TI  - Genome-wide detection of recurring sites of uniparental disomy in follicular and
      transformed follicular lymphoma.
AB  - Single-nucleotide polymorphism (SNP) array analysis was performed using the 10K
      GeneChip array on a series of 26 paired follicular lymphoma (FL) and transformed
      FL (t-FL) biopsies and the lymphoma cell lines SCI-1, DoHH2 and RL2261. Regions
      of acquired homozygosity were detected in 43/52 (83%) primary specimens with a
      mean of 1.7 and 3.0 aberrations in the FL and t-FL, respectively. A notable
      feature was the occurrence of recurring sites of acquired uniparental disomy
      (aUDP) on 6p, 9p, 12q and 17p in cell lines and primary samples. Homozygosity of
      9p and 17p arose predominantly in t-FL and in three cases rendered the cell
      homozygous for a pre-existing mutation of either CDKN2A or TP53. These data
      suggest that mutation precedes mitotic recombination, which leads to the removal
      of the remaining wild-type allele. In all, 18 cases exhibited abnormalities in
      both FL and t-FL samples. In 10 cases blocks of homozygosity were detected in FL
      that were absent in the subsequent t-FL sample. These differences support the
      notion that FL and t-FL may arise in a proportion of patients by divergence from
      a common malignant ancestor cell rather than by clonal evolution from an
      antecedent FL.

PMID- 17495977
TI  - A comprehensive genetic and histopathologic analysis identifies two subgroups of
      B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation.
AB  - The biologic and pathologic features of B-cell malignancies bearing a
      translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 are still
      poorly described. Herein we report the results of a comprehensive cytogenetic,
      fluorescence in situ hybridization (FISH), molecular and histopathological survey
      of a large series of B-cell malignancies with t(14;19) or variant translocations.
      A total of 56 B-cell malignancies with a FISH-proven BCL3 involvement were
      identified with the translocation partners being IGH (n=51), IGL (n=2), IGK (n=2)
      and a non-IG locus (n=1). Hierarchical clustering of chromosomal changes
      associated with the t(14;19) indicated the presence of two different groups of
      IG/BCL3-positive lymphatic neoplasias. The first group included 26 B-cell
      malignancies of various histologic subtypes containing a relatively high number
      of chromosomal changes and mostly mutated IgVH genes. This cluster displayed
      three cytogenetic branches, one with rearrangements in 7q, another with deletions
      in 17p and a third one with rearrangements in 1q and deletions in 6q and 13q. The
      second group included 19 cases, mostly diagnosed as B-cell chronic lymphocytic
      leukemia (B-CLL), and characterized by few additional chromosomal changes (e.g.
      trisomy 12) and unmutated IgVH genes. In conclusion, our study indicates that
      BCL3 translocations are not restricted to B-CLL but present in a heterogeneous
      group of B-cell malignancies.

PMID- 17495978
TI  - A CD19-specific single-chain immunotoxin mediates potent apoptosis of B-lineage
      leukemic cells.
AB  - CD19 is a B-lineage-specific transmembrane signaling protein participating in the
      control of proliferation and differentiation. It is present at high surface
      density on chronic B-lymphocytic leukemia (B-CLL) cells and cells of other B-cell
      malignancies, and is a prime target for therapy with antibody-derived agents.
      Many attempts have been made to target malignant cells via CD19, but to date none
      of these agents have received drug approval. Here we report the design of a
      monovalent immunotoxin consisting of a CD19-specific single-chain Fv antibody
      fragment fused to a derivative of Pseudomonas Exotoxin A. This fusion protein
      induced efficient antigen-restricted apoptosis of several human leukemia- and
      lymphoma-derived cell lines including Nalm-6, which it eliminated at an effective
      concentration (EC(50)) of 2.5 nM. The agent displayed synergistic toxicity when
      used in combination with valproic acid and cyclosporin A in cell-culture assays.
      It induced apoptosis of primary malignant cells in 12/12 samples from B-CLL
      patients, including patients responding poorly to fludarabine, and of cells from
      one pediatric acute lymphoblastic leukemia patient. In NOD/SCID mice transplanted
      with Nalm-6 cells, the toxin prevented engraftment and significantly prolonged
      survival of treated mice. Owing to its efficient antigen-restricted antileukemic
      activity, the agent deserves further development towards clinical testing.

PMID- 17495979
TI  - Possible role of pectin-containing mucilage and dew in repairing embryo DNA of
      seeds adapted to desert conditions.
AB  - BACKGROUND AND AIMS: Repair of damage to DNA of seed embryos sustained during
      long periods of quiescence under dry desert conditions is important for
      subsequent germination. The possibility that repair of embryo DNA can be
      facilitated by small amounts of water derived from dew temporarily captured at
      night by pectinaceous surface pellicles was tested. These pellicles are secreted
      during early seed development and form mucilage when hydrated. METHODS: Seeds of
      Artemisia sphaerocephala and Artemisia ordosica were collected from a sandy
      desert. Their embryos were damaged by gamma radiation to induce a standard level
      of DNA damage. The treated seeds were then exposed to nocturnal dew deposition on
      the surface of soil in the Negev desert highlands. The pellicles were removed
      from some seeds and left intact on others to test the ability of mucilage to
      support repair of the damaged DNA when night-time humidity and temperature
      favoured dew formation. Repair was assessed from fragmentation patterns of
      extracted DNA on agarose gels. KEY RESULTS: For A. sphaerocephala, which has
      thick seed pellicles, DNA repair occurred in seeds with intact pellicles after 50
      min of cumulative night dew formation, but not in seeds from which the pellicles
      had been removed. For A. ordosica, which has thin seed pellicles, DNA repair took
      at least 510 min of cumulative night dewing to achieve partial recovery of DNA
      integrity. The mucilage has the ability to rehydrate after daytime dehydration.
      CONCLUSIONS: The ability of seeds to develop a mucilaginous layer when wetted by
      night-time dew, and to repair their DNA under these conditions, appear to be
      mechanisms that help maintain seed viability under harsh desert conditions.

PMID- 17495980
TI  - Longevity of white clover (Trifolium repens) leaves, stolons and roots, and
      consequences for nitrogen dynamics under northern temperate climatic conditions.
AB  - BACKGROUND AND AIMS: White clover (Trifolium repens) is, due to nitrogen (N)
      fixation, important to the N dynamics of several northern temperate
      agroecosystems. This study aimed at monitoring growth and death of major white
      clover plant organs to assess their potential contribution to within-season N
      input and risk of off-season N losses. METHODS: White clover ('Snowy') was
      studied in a plot and root window experiment in southeast Norway (60 degrees
      42'N, 10 degrees 51'E). Leaves, stolons and roots were tagged for lifespan
      measurement in harvested and unharvested stands during two experimental years.
      The availability of soil inorganic N was measured by plant root simulator (PRS)
      probes. KEY RESULTS: The longevity of leaves and petioles ranged from 21 to 86 d
      (mean = 59 d), of main stolon sections from 111 to over 677 d (mean = 411 d) and
      of roots from 27 to 621 d (mean = 290 d). About 60 % of the leaves produced had
      turned over by the end of the growing season and another 30 % had died or
      disappeared by the subsequent spring. Harvesting reduced the longevity of stolons
      and increased plant fragmentation, but did not decrease leaf or root lifespan or
      increase soil N availability. From the plant organ turnover data, it was
      estimated that the gross N input to the soil-plant system from white clover in
      pure stand during two growing seasons corresponded to a 2.5-fold increase over
      the total N in harvestable shoots. CONCLUSIONS: The short lifespan and poor over
      wintering of leaves showed their potential importance as a nitrogen source in the
      soil-plant ecosystem but also their potential contribution to the risk of off
      season N losses.

PMID- 17495981
TI  - The role of leaf lobation in elongation responses to shade in the rosette-forming
      forb Serratula tinctoria (Asteraceae).
AB  - BACKGROUND AND AIMS: Lobed leaves are considered selectively advantageous in
      conditions of high irradiance. However, most studies have involved woody species,
      with only a few considering the role of leaf lobation in herbaceous rosette
      species. In this study, it is hypothesized that, in addition to its adaptive
      value in high light, leaf lobation may add to the function of petioles as
      vertical spacers in herbaceous species in conditions of strong competition for
      light. METHODS: To test this hypothesis, leaf development was examined under
      seasonally changing natural light conditions and a field experiment was conducted
      in which light climate was manipulated in a wooded meadow population of Serratula
      tinctoria. KEY RESULTS: No changes in leaf lobation were observed in response to
      experimental shading or different natural light conditions. However, in tall
      herbaceous vegetation, plants with highly lobed leaves achieved significantly
      greater vertical elongation than plants with less-lobed leaves. In contrast to
      herbaceous shade, tree shade had no effect on leaf elongation, suggesting
      differential responsiveness to competition from neighbouring herbs versus
      overhead shade. In shading treatments, imposed shade could only be responded to
      by the elongation of leaves that were produced late in development. CONCLUSIONS:
      The results show that extensive leaf lobation can enable greater leaf elongation
      in response to shade from surrounding herbaceous vegetation. The different
      morphological responses displayed by Serratula tinctoria to different types of
      shade demonstrate the importance of critically assessing experimental designs
      when investigating phenotypic plasticity in response to shade.

PMID- 17495982
TI  - Plant KT/KUP/HAK potassium transporters: single family - multiple functions.
AB  - BACKGROUND AND AIMS: Potassium transporters belonging to the KT/KUP/HAK family
      are important for various aspects of plant life including mineral nutrition and
      the regulation of development. Genes encoding these transporters are present in
      the genomes of all plants, but have not been found in the genomes of Protista or
      Animalia. The aim of this Botanical Briefing is to analyse the function of
      KT/KUP/HAK transporters from evolutionary, molecular and physiological
      perspectives. SCOPE: This Briefing covers the phylogeny and evolution of
      KT/KUP/HAK transporters, the role of transporters in plant mineral nutrition and
      potassium homeostasis, and the role of KT/KUP/HAK transporters in plant
      development.

PMID- 17495983
TI  - Finding the way in phenotypic space: the origin and maintenance of constraints on
      organismal form.
AB  - BACKGROUND: One of the all-time questions in evolutionary biology regards the
      evolution of organismal shapes, and in particular why certain forms appear
      repeatedly in the history of life, others only seldom and still others not at
      all. Recent research in this field has deployed the conceptual framework of
      constraints and natural selection as measured by quantitative genetic methods.
      SCOPE: In this paper I argue that quantitative genetics can by necessity only
      provide us with useful statistical summaries that may lead researchers to
      formulate testable causal hypotheses, but that any inferential attempt beyond
      this is unreasonable. Instead, I suggest that thinking in terms of coordinates in
      phenotypic spaces, and approaching the problem using a variety of empirical
      methods (seeking a consilience of evidence), is more likely to lead to solid
      inferences regarding the causal basis of the historical patterns that make up
      most of the data available on phenotypic evolution.

PMID- 17495984
TI  - Hybridization between two polyploid Cardamine (Brassicaceae) species in North
      western Spain: discordance between morphological and genetic variation patterns.
AB  - BACKGROUND AND AIMS: Hybridization is an important evolutionary phenomenon, and
      therefore a detailed understanding of the dynamics of interspecific gene flow and
      resulting morphological and genetic patterns is of widespread interest. Here
      hybridization between the polyploids Cardamine pratensis and C. raphanifolia at
      four localities is explored. Using different types of data, the aim is to provide
      simultaneous and direct comparisons between genotype and phenotype variation
      patterns in the studied hybrid populations. METHODS: Evidence of hybridization
      has been gathered from morphology, molecular markers (amplified fragment length
      polymorphism and chloroplast DNA sequences), pollen viability, karyology and
      nuclear DNA content. KEY RESULTS: All data support extensive gene flow occurring
      in the hybrid populations. A wide range of morphological and genetic variation is
      observed, which includes both parental and intermediate types. Unbalanced pollen
      fertility and several ploidy levels are recorded. CONCLUSIONS: Incongruence
      reported between genotype and phenotype suggests that parental phenotypes are
      affected by introgression, and intermediate hybrid phenotypes can be genetically
      closer to one of the parents. Thus, it is evident that morphology, when used
      alone, can be misleading for interpreting hybridization, and critical evaluation
      of other data is needed.

PMID- 17495985
TI  - Morphological variation among Betula nana (diploid), B. pubescens (tetraploid)
      and their triploid hybrids in Iceland.
AB  - BACKGROUND AND AIMS: Introgressive hybridization between two co-existing Betula
      species in Iceland, diploid dwarf birch B. nana and tetraploid downy birch B.
      pubescens, has been well documented. The two species are highly variable
      morphologically, making taxonomic delineation difficult despite stable ploidy
      levels. Here an analysis is made of morphological variation within each ploidy
      group with an aim to establishing a reliable means to distinguish the species.
      METHODS: Plant materials were collected from 14 woodlands in Iceland. The plants
      were identified based on 2n chromosome numbers. Morphological variation in
      species-specific characters within each ploidy group was analysed qualitatively
      and quantitatively. The morphological index was based on eight discrete
      characters, whereas the multivariate analysis was based on nine leaf variables.
      KEY RESULTS: Of the 461 plants examined, 9.5 % were found to be triploid hybrids.
      The three ploidy groups were morphologically distinguishable but their variation
      overlapped. The diploid, triploid and tetraploid groups had average scores of
      1.3, 4.1 and 8.3, respectively, in the morphology index scale from 0 (B. nana) to
      13 (B. pubescens). A linear discriminant analysis also revealed significant
      separation among the three ploidy groups and the model assigned 96 % and 97 % of
      the B. nana and B. pubescens individuals correctly. The triploid hybrids were
      difficult to predict since only half of them could be assigned correctly. Leaf
      length was the most useful variable identifying triploid hybrids. Geographical
      patterns within the ploidy groups could partly be explained by differences in
      mean July temperature. CONCLUSIONS: Hybridization between B. nana and B.
      pubescens is widespread in Iceland. The species can be distinguished from each
      other morphologically, and from the triploid hybrids. The overlapping
      morphological variation indicates bidirectional introgression between the two
      species via triploid hybrids. Iceland could be considered a birch hybrid zone,
      harbouring genetic variation which may be advantageous in subarctic regions.

PMID- 17495986
TI  - Contrasting patterns in crop domestication and domestication rates: recent
      archaeobotanical insights from the Old World.
AB  - BACKGROUND: Archaeobotany, the study of plant remains from sites of ancient human
      activity, provides data for studying the initial evolution of domesticated
      plants. An important background to this is defining the domestication syndrome,
      those traits by which domesticated plants differ from wild relatives. These
      traits include features that have been selected under the conditions of
      cultivation. From archaeological remains the easiest traits to study are seed
      size and in cereal crops the loss of natural seed dispersal. SCOPE: The rate at
      which these features evolved and the ordering in which they evolved can now be
      documented for a few crops of Asia and Africa. This paper explores this in
      einkorn wheat (Triticum monococcum) and barley (Hordeum vulgare) from the Near
      East, rice (Oryza sativa) from China, mung (Vigna radiata) and urd (Vigna mungo)
      beans from India, and pearl millet (Pennisetum glaucum) from west Africa. Brief
      reference is made to similar data on lentils (Lens culinaris), peas (Pisum
      sativum), soybean (Glycine max) and adzuki bean (Vigna angularis). Available
      quantitative data from archaeological finds are compiled to explore changes with
      domestication. The disjunction in cereals between seed size increase and
      dispersal is explored, and rates at which these features evolved are estimated
      from archaeobotanical data. Contrasts between crops, especially between cereals
      and pulses, are examined. CONCLUSIONS: These data suggest that in domesticated
      grasses, changes in grain size and shape evolved prior to non-shattering ears or
      panicles. Initial grain size increases may have evolved during the first
      centuries of cultivation, within perhaps 500-1000 years. Non-shattering
      infructescences were much slower, becoming fixed about 1000-2000 years later.
      This suggests a need to reconsider the role of sickle harvesting in
      domestication. Pulses, by contrast, do not show evidence for seed size increase
      in relation to the earliest cultivation, and seed size increase may be delayed by
      2000-4000 years. This implies that conditions that were sufficient to select for
      larger seed size in Poaceae were not sufficient in Fabaceae. It is proposed that
      animal-drawn ploughs (or ards) provided the selection pressure for larger seeds
      in legumes. This implies different thresholds of selective pressure, for example
      in relation to differing seed ontogenetics and underlying genetic architecture in
      these families. Pearl millet (Pennisetum glaucum) may show some similarities to
      the pulses in terms of a lag-time before truly larger-grained forms evolved.

PMID- 17495987
TI  - Low-grade albuminuria and the incidence of heart failure in a community-based
      cohort of elderly men.
AB  - AIMS: To investigate associations of urinary albumin excretion rate (UAER) and
      heart failure (HF) incidence in a community-based sample. METHODS AND RESULTS: In
      a prospective study of 70-year-old men free from HF at baseline (n = 1106), UAER
      (from timed overnight samples) was analysed with established risk factors for HF
      [acute MI before baseline, acute MI during follow-up (modelled as a time
      dependent covariate), hypertension, diabetes, left ventricular hypertrophy,
      smoking, body mass index, and glomerular filtration rate] and more recently
      described risk factors [high-sensitive C-reactive protein and insulin sensitivity
      (clamp glucose disposal rate)] as predictors of HF incidence. Ninety-eight
      participants developed HF during a median follow-up of 9.0 years. In Cox
      proportional hazards models adjusted for established and novel risk factors for
      HF, a 1 SD increase in log UAER increased the risk of HF in individuals without
      anti-hypertensive treatment (hazard ratio 1.49; 95% CI 1.13-1.98; P = 0.005).
      Furthermore, UAER remained an independent predictor of HF, also in participants
      without diabetes at baseline or myocardial infarction at baseline or during
      follow-up. There were no significant associations between UAER and HF incidence
      in individuals with anti-hypertensive treatment. CONCLUSION: Our observations
      support the notion that low-grade albuminuria is a marker for subclinical
      cardiovascular damage that predisposes to future HF in the community.

PMID- 17495988
TI  - Post-traumatic stress disorder in the context of terrorism and other civil
      conflict in Northern Ireland: randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of cognitive therapy for post-traumatic
      stress disorder related to terrorism and other civil conflict in Northern
      Ireland. DESIGN: Randomised controlled trial. SETTING: Community treatment
      centre, Northern Ireland. PARTICIPANTS: 58 consecutive patients with chronic post
      traumatic stress disorder (median 5.2 years, range 3 months to 32 years) mostly
      resulting from multiple traumas linked to terrorism and other civil conflict.
      INTERVENTIONS: Immediate cognitive therapy compared with a waiting list control
      condition for 12 weeks followed by treatment. Treatment comprised a mean of 5.9
      sessions during 12 weeks and 2.0 sessions thereafter. MAIN OUTCOME MEASURES:
      Primary outcome measures were patients' scores for post-traumatic stress disorder
      (post-traumatic stress diagnostic scale) and depression (Beck depression
      inventory). The secondary outcome measure was scores for occupational and social
      functioning (work related disability, social disability, and family related
      disability) on the Sheehan disability scale. RESULTS: At 12 weeks after
      randomisation, immediate cognitive therapy was associated with significantly
      greater improvement than the waiting list control group in the symptoms of post
      traumatic stress disorder (mean difference 9.6, 95% confidence interval 3.6 to
      15.6), depression (mean difference 10.1, 4.8 to 15.3), and self reported
      occupational and social functioning (mean difference 1.3, 0.3 to 2.5). Effect
      sizes from before to after treatment were large: post-traumatic stress disorder
      1.25, depression 1.05, and occupational and social functioning 1.17. No change
      was observed in the control group. CONCLUSION: Cognitive therapy is an effective
      treatment for post-traumatic stress disorder related to terrorism and other civil
      conflict. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16228473
      [controlled-trials.com].

PMID- 17495989
TI  - 'Smoke gets in your eyes': a research-informed professional education and
      advocacy programme.
AB  - Smoking is associated with common sight-threatening eye conditions. We suspected
      that this link was little known and it might be a potent novel health promotional
      tool. We therefore developed a programme ultimately aiming to reduce the burden
      of eye disease attributable to smoking. The programme aims were to (1) raise
      awareness of the link between smoking and eye disease and advocate changes in
      relevant policies and (2) investigate and promote change in professional practice
      so that smokers are identified and routinely offered smoking cessation
      advice/support in eyecare settings. An inter-professional team developed a
      programme of research and education targeting policy-makers, healthcare
      professionals, the public and patients. We reviewed evidence about the causal
      link between smoking and eye disease, researched current awareness of the link,
      researched current practice of eyecare health professionals, produced health
      education materials and campaigned for policy changes. The series of projects was
      completed successfully, achieving media coverage, confirming the causal link
      between smoking and eye disease and demonstrating low awareness of this
      association. Healthcare leaders and policy-makers were engaged in our programme
      resulting in commitment, in principle, from the UK's Chief Medical Officer and
      the European Commission to consider including warning labels related to blindness
      on cigarette packets.

PMID- 17495990
TI  - Trends in admissions to hospital involving an assault using a knife or other
      sharp instrument, England, 1997-2005.
AB  - OBJECTIVES: To investigate recent trends in in-patient admissions in England for
      assaults that involve a stabbing. Design and data source Time-series analysis of
      the NHS Health and Social Care Information Centre's Hospital Episode Statistics
      (HES) database. Setting England, April 1997 to March 2005. Main outcome measure
      All completed hospital admissions with a mention of assault by sharp object
      (International Classification of Diseases, Tenth Revision, code X99) in the
      relevant diagnosis fields in HES. RESULTS: In the eight years between 1st April
      1997 and 31st March 2005 the number of people admitted to hospital reportedly
      following an assault involving a sharp object rose by 30%, from 3770 patients in
      1997/8 to 4891 in 2004/5. One hundred and fifty-four of these people died (0.5%).
      Forty-two percent (14 220) of admissions were on a Saturday or Sunday. Males
      accounted for 90% (males 30 464 and females 3406) of admissions. Forty-nine
      percent (14 786) of the men, and 41% (1383) of the women, had injuries to the
      head, neck or thorax. CONCLUSIONS: The number of recorded hospital admissions
      from stabbing assaults increased between 1997 and 2005. Approximately 13 people a
      day are currently admitted to hospital for treatment after being stabbed. Further
      research is required to identify effective interventions to reduce the number of
      stabbings.

PMID- 17495991
TI  - Developing the public health role of a front line clinical service: integrating
      stop smoking advice into routine podiatry services.
AB  - BACKGROUND: Although smoking is a major public health problem, many clinicians do
      not routinely provide evidence-based health improvement advice to smokers to help
      them to quit. METHODS: Plan, Do, Study, Act (PDSA) cycle methodology was used to
      design and implement a service development so that health improvement advice for
      smokers featured in all podiatry consultations provided by a Primary Care Trust
      in North East England. IT systems were developed to record the number and
      proportion of patients for whom smoking status was assessed, and the number and
      proportion of smokers who were given advice to quit and referred for specialist
      support. A questionnaire to staff explored their perceptions of the development
      on their clinics and consultations. RESULTS: During a 6-month period, smoking
      status was recorded for all 8831 (100%) patients attending podiatry clinics; 83%
      of smokers were given brief advice to quit; 7% of smokers were given help to
      access specialist stop smoking support services. Improvements were introduced
      within existing budgets and did not prolong clinics. CONCLUSIONS: It is
      straightforward and inexpensive to develop clinical services so that public
      health guidance is routinely implemented. More widespread implementation of
      similar service developments could lead to national improvements in public
      health.

PMID- 17495992
TI  - Organizational change--key to capacity building and effective health promotion.
AB  - Contemporary health promotion is now a well-defined discipline with a strong
      (albeit diverse) theoretical base, proven technologies (based on program
      planning) for addressing complex social problems, processes to guide practice and
      a body of evidence of efficacy and increasingly, effectiveness. Health promotion
      has evolved principally within the health sector where it is frequently
      considered optional rather than core business. To maximize effectiveness, quality
      health promotion technologies and practices need to be adopted as core business
      by the health sector and by organizations in other sectors. It has proven
      difficult to develop the infrastructure, workforce and resource base needed to
      ensure the routine introduction of high-quality health promotion into
      organizations. Recognizing these problems, this paper explores the use of
      organizational theory and practice in building the capacity of organizations to
      design, deliver and evaluate health promotion effectively and efficiently. The
      paper argues that organizational change is an essential but under-recognized
      function for the sustainability of health promotion practice and a necessary
      component of capacity-building frameworks. The interdependence of quality health
      promotion with organizational change is discussed in this paper through three
      case studies. While each focused on different aspects of health promotion
      development, the centrality of organizational change in each of them was
      striking. This paper draws out elements of organizational change to demonstrate
      that health promotion specialists and practitioners, wherever they are located,
      should be building organizational change into both their practice and capacity
      building frameworks because without it, effectiveness and sustainability are at
      risk.

PMID- 17495993
TI  - Managerial attitudes on the development of health promoting hospitals in Beijing.
AB  - In 2002, the Beijing Committee for Disease Prevention launched guidelines based
      on the Ottawa Charter for Health Promotion on health promoting hospitals (HPHs).
      HPH pilot projects were then initiated, on a voluntary basis, in 44 Beijing
      hospitals. Evaluations have been undertaken to assess the impacts of the pilot
      project. This article outlines this HPH project, its development and evaluation
      and reports on the attitudes and contribution of hospital management as
      determined by questionnaires and interviews from 281 managerial employees from
      106 Beijing hospitals (93 from pilot hospitals and 188 from control). The results
      of the evaluation indicate that long-term health promotion planning and health
      promotion specialized funds have been better established in pilot hospitals than
      in the control group and also that the concept of HPH is better understood by
      managerial staff in pilot hospitals than by those in control hospitals. The main
      perceived barriers faced in the development of HPH are shortages of funds,
      personnel, time management and professional skills. To further develop HPHs in
      China, effort needs to be made to ensure that hospital leaders and management are
      considered first. If managerial staff have an appropriate understanding of the
      concept and principles of HPH, then it is more likely that health promotion
      activities can be introduced into the daily workings of hospitals, and the
      necessary funds, personnel and training on health promotion skills be provided.

PMID- 17495995
TI  - Nucleotide composition string selection in HIV-1 subtyping using whole genomes.
AB  - MOTIVATION: The availability of the whole genomic sequences of HIV-1 viruses
      provides an excellent resource for studying the HIV-1 phylogenies using all the
      genetic materials. However, such huge volumes of data create computational
      challenges in both memory consumption and CPU usage. RESULTS: We propose the
      complete composition vector representation for an HIV-1 strain, and a string
      scoring method to extract the nucleotide composition strings that contain the
      richest evolutionary information for phylogenetic analysis. In this way, a large
      scale whole genome phylogenetic analysis for thousands of strains can be done
      both efficiently and effectively. By using 42 carefully curated strains as
      references, we apply our method to subtype 1156 HIV-1 strains (10.5 million
      nucleotides in total), which include 825 pure subtype strains and 331
      recombinants. Our results show that our nucleotide composition string selection
      scheme is computationally efficient, and is able to define both pure subtypes and
      recombinant forms for HIV-1 strains using the 5000 top ranked nucleotide strings.
      AVAILABILITY: The Java executable and the HIV-1 datasets are accessible through
      'http://www.cs.ualberta.ca/~ghlin/src/WebTools/hiv.php. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 17495996
TI  - Biological network mapping and source signal deduction.
AB  - MOTIVATION: Many biological networks, including transcriptional regulation,
      metabolism, and the absorbance spectra of metabolite mixtures, can be represented
      in a bipartite fashion. Key to understanding these bipartite networks are the
      network architecture and governing source signals. Such information is often
      implicitly imbedded in the data. Here we develop a technique, network component
      mapping (NCM), to deduce bipartite network connectivity and regulatory signals
      from data without any need for prior information. RESULTS: We demonstrate the
      utility of our approach by analyzing UV-vis spectra from mixtures of metabolites
      and gene expression data from Saccharomyces cerevisiae. From UV-vis spectra,
      hidden mixing networks and pure component spectra (sources) were deduced to a
      higher degree of resolution with our method than other current bipartite
      techniques. Analysis of S. cerevisiae gene expression from two separate
      environmental conditions (zinc and DTT treatment) yielded transcription networks
      consistent with ChIP-chip derived network connectivity. Due to the high degree of
      noise in gene expression data, the transcription network for many genes could not
      be inferred. However, with relatively clean expression data, our technique was
      able to deduce hidden transcription networks and instances of combinatorial
      regulation. These results suggest that NCM can deduce correct network
      connectivity from relatively accurate data. For noisy data, NCM yields the
      sparsest network capable of explaining the data. In addition, partial knowledge
      of the network topology can be incorporated into NCM as constraints.
      AVAILABILITY: Algorithm available on request from the authors. Soon to be posted
      on the web, http://www.seas.ucla.edu/~liaoj/. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 17495997
TI  - PLMaddon: a power-law module for the Matlab SBToolbox.
AB  - PLMaddon is a General Public License (GPL) software module designed to expand the
      current version of the SBToolbox (a Matlab toolbox for systems biology;
      www.sbtoolbox.org) with a set of functions for the analysis of power-law models,
      a specific class of kinetic models, set in ordinary differential equations (ODE)
      and in which the kinetic orders can have positive/negative non-integer values.
      The module includes functions to generate power-law Taylor expansions of other
      ODE models (e.g. Michaelis-Menten type models), as well as algorithms to estimate
      steady-states. The robustness and sensitivity of the models can also be analysed
      and visualized by computing the power-law's logarithmic gains and sensitivities.

PMID- 17495998
TI  - MutationFinder: a high-performance system for extracting point mutation mentions
      from text.
AB  - Discussion of point mutations is ubiquitous in biomedical literature, and
      manually compiling databases or literature on mutations in specific genes or
      proteins is tedious. We present an open-source, rule-based system,
      MutationFinder, for extracting point mutation mentions from text. On blind test
      data, it achieves nearly perfect precision and a markedly improved recall over a
      baseline. AVAILABILITY: MutationFinder, along with a high-quality gold standard
      data set, and a scoring script for mutation extraction systems have been made
      publicly available. Implementations, source code and unit tests are available in
      Python, Perl and Java. MutationFinder can be used as a stand-alone script, or
      imported by other applications. PROJECT URL: http://bionlp.sourceforge.net.

PMID- 17495999
TI  - WilcoxCV: an R package for fast variable selection in cross-validation.
AB  - In the last few years, numerous methods have been proposed for microarray-based
      class prediction. Although many of them have been designed especially for the
      case n << p (much more variables than observations), preliminary variable
      selection is almost always necessary when the number of genes reaches several
      tens of thousands, as usual in recent data sets. In the two-class setting, the
      Wilcoxon rank sum test statistic is, with the t-statistic, one of the standard
      approaches for variable selection. It is well known that the variable selection
      step must be seen as a part of classifier construction and, as such, be performed
      based on training data only. When classifier accuracy is evaluated via cross
      validation or Monte-Carlo cross-validation, it means that we have to perform p
      Wilcoxon or t-tests for each iteration, which becomes a daunting task for
      increasing p. As a consequence, many authors often perform variable selection
      only once using all the available data, which can induce a dramatic
      underestimation of error rate and thus lead to misleadingly reporting predictive
      power. We propose a very fast implementation of variable selection based on the
      Wilcoxon test for use in cross-validation and Monte Carlo cross-validation (also
      known as random splitting into learning and test sets). This implementation is
      based on a simple mathematical formula using only the ranks calculated from the
      original data set. AVAILABILITY: Our method is implemented in the freely
      available R package WilcoxCV which can be downloaded from the Comprehensive R
      Archive Network at http://cran.r
      project.org/src/contrib/Descriptions/WilcoxCV.html.

PMID- 17496000
TI  - Data reduction of isotope-resolved LC-MS spectra.
AB  - MOTIVATION: Data reduction of liquid chromatography-mass spectrometry (LC-MS)
      spectra can be a challenge due to the inherent complexity of biological samples,
      noise and non-flat baseline. We present a new algorithm, LCMS-2D, for reliable
      data reduction of LC-MS proteomics data. RESULTS: LCMS-2D can reliably reduce LC
      MS spectra with multiple scans to a list of elution peaks, and subsequently to a
      list of peptide masses. It is capable of noise removal, and deconvoluting peaks
      that overlap in m/z, in retention time, or both, by using a novel iterative peak
      picking step, a 'rescue' step, and a modified variable selection method. LCMS-2D
      performs well with three sets of annotated LC-MS spectra, yielding results that
      are better than those from PepList, msInspect and the vendor software BioAnalyst.
      AVAILABILITY: The software LCMS-2D is available under the GNU general public
      license from http://www.bioc.aecom.yu.edu/labs/angellab/as a standalone C program
      running on LINUX.

PMID- 17496001
TI  - Retraction. Dynamics of pulmonary O2 uptake, leg blood flow and muscle
      deoxygenation during heavy-intensity exercise in young adults.

PMID- 17496002
TI  - Superoxide dismutase mimetic tempol inhibits hypoxic pulmonary vasoconstriction
      in rats independently of nitric oxide production.
AB  - Hypoxic pulmonary vasoconstriction (HPV), an important physiological mechanism,
      is regulated by changes in the production of and interactions among reactive
      oxygen species (ROS). There is controversy, however, over whether HPV is mediated
      by an increase or a decrease in ROS production. Also, the role of NO in HPV
      remains unclear. The aim of this study was to investigate whether the inhibition
      of HPV by the antioxidant tempol was dependent on the concentration of NO, and
      how its effect was influenced by increased basal pulmonary vascular tone. In
      isolated rat lungs, we measured vasoconstrictor responses to acute ventilatory
      hypoxia before and after administration of tempol during perfusion with or
      without L-NAME. We found that tempol abolished HPV independently of NO
      production. When we increased basal vascular tone by K(+)-induced depolarization,
      we also found that tempol completely inhibited HPV. Our results indicate that
      inhibition of HPV by the superoxide dismutase mimetic tempol does not depend on
      either NO production or a decrease in basal vascular tone.

PMID- 17496003
TI  - Blood volume analysis: a new technique and new clinical interest reinvigorate a
      classic study.
AB  - Blood volume studies using the indicator dilution technique and radioactive
      tracers have been performed in nuclear medicine departments for over 50 y. A
      nuclear medicine study is the gold standard for blood volume measurement, but the
      classic dual-isotope blood volume study is time-consuming and can be prone to
      technical errors. Moreover, a lack of normal values and a rubric for
      interpretation made volume status measurement of limited interest to most
      clinicians other than some hematologists. A new semiautomated system for blood
      volume analysis is now available and provides highly accurate results for blood
      volume analysis within only 90 min. The availability of rapid, accurate blood
      volume analysis has brought about a surge of clinical interest in using blood
      volume data for clinical management. Blood volume analysis, long a low-volume
      nuclear medicine study all but abandoned in some laboratories, is poised to enter
      the clinical mainstream. This article will first present the fundamental
      principles of fluid balance and the clinical means of volume status assessment.
      We will then review the indicator dilution technique and how it is used in
      nuclear medicine blood volume studies. We will present an overview of the new
      semiautomated blood volume analysis technique, showing how the study is done, how
      it works, what results are provided, and how those results are interpreted.
      Finally, we will look at some of the emerging areas in which data from blood
      volume analysis can improve patient care. The reader will gain an understanding
      of the principles underlying blood volume assessment, know how current nuclear
      medicine blood volume analysis studies are performed, and appreciate their
      potential clinical impact.

PMID- 17496004
TI  - The value of quantitative uptake of (99m)Tc-MDP and (99m)Tc-HMPAO white blood
      cells in detecting osteomyelitis in violated peripheral bones.
AB  - Our objective in this study was to evaluate whether measurement of quantitative
      uptake of (99m)Tc-methylene diphosphate (MDP) and (99m)Tc
      hexamethylpropyleneamine oxime (HMPAO) white blood cells (WBCs) is useful in
      detecting osteomyelitis in peripheral bony lesions. METHODS: Twenty-four patients
      (12 men and 12 women; age range, 25-72 y) were referred for imaging because of
      clinically suspected osteomyelitis. They had a traumatic fracture (n = 10), knee
      prosthesis (n = 5), hip prosthesis (n = 2), diabetic foot (n = 4), or chronic
      osteomyelitis (n = 3). Three-phase bone scanning and (99m)Tc-HMPAO WBC studies
      were performed on all patients within the same week. Regions of interest were
      drawn over the abnormal bony sites and the contralateral normal sites, and the
      abnormal-to-normal uptake ratios (A/N ratios) were obtained for both studies.
      RESULTS: All patients had abnormal findings on 3-phase bone scanning, whereas 17
      (71%) had abnormal findings on (99m)Tc-HMPAO WBC studies, of which 15 were
      confirmed to be true-positive. In those 15 patients, the mean A/N ratios for
      (99m)Tc-MDP and (99m)Tc-HMPAO WBC were 3.0 +/- 1.6 (range, 1.3-6.2) and 1.8 +/-
      0.3 (range, 1.4-2.2), respectively. In the other 9 patients, whose scan results
      were clinically confirmed to be true-negative, the mean A/N ratios for (99m)Tc
      MDP and (99m)Tc-HMPAO WBC were 2.1 +/- 1.2 and 1.2 +/- 0.2, respectively. In the
      group with a (99m)Tc-MDP A/N ratio greater than 2 (n = 15), 87% (13/15) had a
      high (99m)Tc-HMPAO WBC A/N ratio (>1.5), including 2 that were false-positive. In
      the remaining 2 patients, one with chronic osteomyelitis and the other with a
      recent hip prosthesis, (99m)Tc-HMPAO WBC ratios were normal. In the group with a
      bone A/N ratio of less than 2 (n = 9), only 4 patients (44%) were true-positive
      for acute osteomyelitis. CONCLUSION: (99m)Tc-MDP bone scanning alone, with an A/N
      ratio of more than 2, is useful in detecting osteomyelitis in violated bone
      except in the case of a recent hip prosthesis or chronic osteomyelitis.

PMID- 17496005
TI  - Substitution of oral (18)F-FDG for intravenous (18)F-FDG in PET scanning.
AB  - The aim of this study was to see whether oral administration of (18)F-FDG could
      be substituted-without significant loss of information-for intravenous injection
      of (18)F-FDG in patients with difficult intravenous access of any cause, such as
      that often seen in cancer patients after many cycles of chemotherapy. METHODS:
      PET after both oral and intravenous administration of (18)F-FDG was performed on
      2 healthy volunteers and 7 patients. An interval of 48 h was maintained between
      the oral administration and the intravenous administration. All scans were
      visually analyzed. Semiquantitative analysis of specific areas was done by
      calculating standardized uptake values (SUVs). Scanning was performed 60 min
      after intravenous tracer administration and 90 min after oral tracer
      administration. RESULTS: All lesions seen after intravenous administration were
      visualized on the oral study as well. SUVs were lower on the oral study than on
      the intravenous study. CONCLUSION: Oral (18)F-FDG can successfully be substituted
      for intravenous (18)F-FDG in patients with difficult intravenous access. However,
      because of the large amount of (18)F-FDG retained in the gut, careful
      interpretation will be required when disease of the gastrointestinal tract is
      being evaluated.

PMID- 17496006
TI  - Improved detection and localization of lower gastrointestinal hemorrhage using
      subtraction scintigraphy: clinical evaluation.
AB  - Does subtraction scintigraphy improve the diagnostic utility of scintigraphic
      evaluation in acute lower gastrointestinal hemorrhage? METHODS: This research was
      a retrospective clinical study using a repeat-measures design of randomized
      control and experimental groups. A single patient dataset provided both the
      control group (conventional scintigraphy) and the experimental group
      (conventional and subtraction techniques). Forty-nine raw (99m)Tc-red blood cell
      studies were randomized and interpreted by 4 independent physicians as
      conventional scintigraphy data only (round 1). The conventional scintigraphy
      studies were combined with subtraction images and randomized for reinterpretation
      (round 2). RESULTS: Although there was a decrease in the mean, no statistically
      significant difference was noted between the mean time to bleed detection between
      interpretive rounds 1 and 2 (P = 0.524). The addition of subtraction scintigraphy
      to the interpretation process changed the outcome from "probably present" to
      "absent" for 14% of patients and from "equivocal" to "absent" for another 12%,
      and this change had a marked effect on the false-positive rate. The false
      positive rate decreased from 9.6% in round 1 to 3.6% in round 2. Receiver
      operator characteristic analysis showed that combining conventional scintigraphy
      with subtraction scintigraphy improved test performance. CONCLUSION: False
      positive studies can be reduced by using subtraction scintigraphy in conjunction
      with conventional scintigraphy in the interpretive process.

PMID- 17496007
TI  - Prevalence, challenges, and solutions for (18)F-FDG PET studies of obese
      patients: a technologist's perspective.
AB  - Obesity has reached epidemic proportions in the United States; hence, it is
      frequently encountered in patients undergoing (18)F-FDG PET studies. The purpose
      of the current study was to present a technologist's perspective on the
      prevalence of obesity and the challenges and solutions in imaging obese patients
      in our PET facility. METHODS: From October 2002 to October 2003, whole-body (18)F
      FDG PET was performed on 1,164 patients with a known or suspected malignancy.
      Images were acquired 45-60 min after (18)F-FDG injection (7.4 MBq [0.2 mCi]/kg,
      with a maximum of 925 MBq [25 mCi]) on a PET scanner using a 4-min emission and 3
      min transmission time per bed position. A database was maintained of patient
      height and weight, and body mass index (BMI) was calculated. Patient obesity was
      classified as overweight (BMI > or = 25 kg/m(2)), obese (BMI > or = 30 kg/m(2)),
      or malignantly obese (BMI > or = 40 kg/m(2)). In addition, PET technologists
      recorded any problems and attempted solutions related to the patient weight.
      RESULTS: BMI calculations showed that 528 patients (45.4%) were overweight or
      obese (322 men and 206 women; mean age, 55 y). Of those, 201 (38%) were
      overweight, 270 (51%) were obese, and 57 (11%) were malignantly obese. Problems
      encountered in these patients included difficult intravenous access (15%),
      difficult patient positioning (10%), patient motion (7%), an incomplete study
      (emission only) (1%), and potentially higher radiation exposure to the
      technologist because of extra time spent near the patient. Attempted solutions
      included adjusting the schedule to allow more time per patient, adjusting the
      dose based on body weight, using varied positioning techniques, dividing the
      study to allow a respite between different image combinations, and dividing time
      spent with obese patients among the technologists involved. CONCLUSION: Excessive
      body weight and related problems have commonly been encountered in our PET
      facility. (18)F-FDG PET studies of obese patients represent an ongoing challenge,
      which requires patient-tailored solutions to avoid compromising image quality and
      risking higher radiation exposure to the technologists.

PMID- 17496008
TI  - Inter- and intraobserver variability of (99m)Tc-DMSA renal scintigraphy: impact
      of oblique views.
AB  - (99m)Tc-Dimercaptosuccinic acid (DMSA) scintigraphy is a frequently used
      diagnostic test to assess the presence and severity of cortical damage. The aim
      of this study is to investigate the variability in the interpretation of (99m)Tc
      DMSA scans, evaluate the usefulness of oblique images, and assess their impact on
      scan interpretation. METHODS: Two experienced nuclear medicine physicians
      independently interpreted 100 (99m)Tc-DMSA scans (197 kidneys) 4 times.
      Interpretation was twice based on posterior projection images and twice based on
      posterior and posterior oblique projection images. For each kidney, the observers
      had to choose between the following results: normal, abnormal, and indeterminate.
      The indices of variability used were the percentage of agreement, kappa
      statistic, and marginal homogeneity. RESULTS: Intraobserver and interobserver
      reproducibility (kappa-values) varied between 0.683 and 0.708 and between 0.609
      and 0.671, respectively, for posterior images. Disagreement in (99m)Tc-DMSA scan
      interpretation occurred in 18% of kidneys within observers and in 21% of kidneys
      between observers when only posterior images were used. Oblique views changed the
      interpretation in 14% and 11.5% of kidneys for the first and second observers,
      respectively. The use of oblique views increased the agreement rate within and
      between observers (kappa-values, 0.725-0.812 and 0.768-0.732, respectively; mean
      agreement, 86.5 and 87.25, respectively). CONCLUSION: Oblique views were found
      useful in approximately 13% of kidneys and affected inter- and intraobserver
      variability. Our results suggest that oblique views should be used routinely in
      children with clinically suspected urinary tract infection to reliably interpret
      images.

PMID- 17496009
TI  - Subtraction SPECT for parathyroid scintigraphy based on maximization of mutual
      information.
AB  - Our objective was to investigate the feasibility of subtraction for SPECT images
      of (99m)Tc-MIBI double-phase parathyroid scintigraphy. METHODS: Fourteen patients
      with hyperparathyroidism were enrolled in the present study. Histopathologically,
      excised tissue specimens showed hyperplasia in 11 patients and adenoma in 3
      patients. Both ultrasonography and (99m)Tc-sestamibi (MIBI) SPECT images were
      obtained from all patients. As standard lines to ensure that patient positioning
      remained identical between the different phases, we used the cross-marker
      produced by a pair of laser pointers, the orbitomeatal line, and the vertical
      midline through the patient's nose. Data processing was performed with software
      that enables image registration by maximization of mutual information. The
      results of subtraction SPECT imaging were compared with those of ultrasonography.
      RESULTS: The registration of double-phase SPECT images was successful in all
      patients when the salivary glands were excluded from the image reconstruction
      region. The overall sensitivities of scintigraphy and ultrasonography were 90.9%
      (40/44) and 70.5% (31/44), respectively, with respective specificities of 83.3%
      (10/12) and 75.0% (9/12). Scintigraphy and ultrasonography showed accuracies of
      92.8% (52/56) and 71.4% (40/56), respectively. CONCLUSION: The new technique used
      in the present study allowed the subtraction for SPECT images. The sensitivity of
      parathyroid lesion detection using this technique was superior to that of
      ultrasonography.

PMID- 17496010
TI  - An introduction to Na(18)F bone scintigraphy: basic principles, advanced imaging
      concepts, and case examples.
AB  - Na(18)F, an early bone scintigraphy agent, is poised to reenter mainstream
      clinical imaging with the present generations of stand-alone PET and PET/CT
      hybrid scanners. (18)F PET scans promise improved imaging quality for both benign
      and malignant bone disease, with significantly improved sensitivity and
      specificity over conventional planar and SPECT bone scans. In this article, basic
      acquisition information will be presented along with examples of studies related
      to oncology, sports medicine, and general orthopedics. The use of image fusion of
      PET bone scans with CT and MRI will be demonstrated. The objectives of this
      article are to provide the reader with an understanding of the history of early
      bone scintigraphy in relation to Na(18)F scanning, a familiarity with basic
      imaging techniques for PET bone scanning, an appreciation of the extent of
      disease processes that can be imaged with PET bone scanning, an appreciation for
      the added value of multimodality image fusion with bone disease, and a
      recognition of the potential role PET bone scanning may play in clinical imaging.

PMID- 17496011
TI  - Nucleation and growth of insulin fibrils in bulk solution and at hydrophobic
      polystyrene surfaces.
AB  - A technique was developed for studying the nucleation and growth of fibrillar
      protein aggregates. Fourier transform infrared and attenuated total reflection
      spectroscopy were used to measure changes in the intermolecular beta-sheet
      content of bovine pancreatic insulin in bulk solution and on model polystyrene
      (PS) surfaces at pH 1. The kinetics of beta-sheet formation were shown to evolve
      in two stages. Combined Fourier transform infrared, dynamic light scattering,
      atomic force microscopy, and thioflavin-T fluorescence measurements confirmed
      that the first stage in the kinetics was related to the formation of nonfibrillar
      aggregates that have a radius of 13 +/- 1 nm. The second stage was found to be
      associated with the growth of insulin fibrils. The beta-sheet kinetics in this
      second stage were used to determine the nucleation and growth rates of fibrils
      over a range of temperatures between 60 degrees C and 80 degrees C. The
      nucleation and growth rates were shown to display Arrhenius kinetics, and the
      associated energy barriers were extracted for fibrils formed in bulk solution and
      at PS surfaces. These experiments showed that fibrils are nucleated more quickly
      in the presence of hydrophobic PS surfaces but that the corresponding fibril
      growth rates decrease. These observations are interpreted in terms of the
      differences in the attempt frequencies and energy barriers associated with the
      nucleation and growth of fibrils. They are also discussed in the context of
      differences in protein concentration, mobility, and conformational and colloidal
      stability that exist between insulin molecules in bulk solution and those that
      are localized at hydrophobic PS interfaces.

PMID- 17496012
TI  - Theoretical analysis of an iron mineral-based magnetoreceptor model in birds.
AB  - Sensing the magnetic field has been established as an essential part of
      navigation and orientation of various animals for many years. Only recently has
      the first detailed receptor concept for magnetoreception been published based on
      histological and physical results. The considered mechanism involves two types of
      iron minerals (magnetite and maghemite) that were found in subcellular
      compartments within sensory dendrites of the upper beak of several bird species.
      But so far a quantitative evaluation of the proposed receptor is missing. In this
      article, we develop a theoretical model to quantitatively and qualitatively
      describe the magnetic field effects among particles containing iron minerals. The
      analysis of forces acting between these subcellular compartments shows a
      particular dependence on the orientation of the external magnetic field. The iron
      minerals in the beak are found in the form of crystalline maghemite platelets and
      assemblies of magnetite nanoparticles. We demonstrate that the pull or push to
      the magnetite assemblies, which are connected to the cell membrane, may reach a
      value of 0.2 pN -- sufficient to excite specific mechanoreceptive membrane
      channels in the nerve cell. The theoretical analysis of the assumed
      magnetoreceptor system in the avian beak skin clearly shows that it might indeed
      be a sensitive biological magnetometer providing an essential part of the
      magnetic map for navigation.

PMID- 17496013
TI  - Membrane insertion and bilayer perturbation by antimicrobial peptide CM15.
AB  - Antimicrobial peptides (AMPs) are an important component of innate immunity and
      have generated considerable interest as a potential new class of antibiotic. The
      biological activity of AMPs is strongly influenced by peptide-membrane
      interactions; however, for many of these peptides the molecular details of how
      they disrupt and/or translocate across target membranes are not known. CM15 is a
      linear, synthetic hybrid AMP composed of the first seven residues of the cecropin
      A and residues 2-9 of the bee venom peptide mellitin. Previous studies have shown
      that upon membrane binding CM15 folds into an alpha-helix with its helical axis
      aligned parallel to the bilayer surface and have implicated the formation of 2.2
      3.8 nm pores in its bactericidal activity. Here we report site-directed spin
      labeling electron paramagnetic resonance studies examining the behavior of CM15
      analogs labeled with a methanethiosulfonate spin label (MTSL) and a brominated
      MTSL as a function of increasing peptide concentration and utilize phospholipid
      analog spin labels to assess the effects of CM15 binding and accumulation on the
      physical properties of membrane lipids. We find that as the concentration of
      membrane-bound CM15 is increased the N-terminal domain of the peptide becomes
      more deeply immersed in the lipid bilayer. Only minimal changes are observed in
      the rotational dynamics of membrane lipids, and changes in lipid dynamics are
      confined primarily to near the membrane surface. However, the accumulation of
      membrane-bound CM15 dramatically increases accessibility of lipid-analog spin
      labels to the polar relaxation agent, nickel (II) ethylenediaminediacetate,
      suggesting an increased permeability of the membrane to polar solutes. These
      results are discussed in relation to the molecular mechanism of membrane
      disruption by CM15.

PMID- 17496014
TI  - Hydrodynamic interactions between two swimming bacteria.
AB  - This article evaluates the hydrodynamic interactions between two swimming
      bacteria precisely. We assume that each bacterium is force free and torque free,
      with a Stokes flow field around it. The geometry of each bacterium is modeled as
      a spherical or spheroidal body with a single helical flagellum. The movements of
      two interacting bacteria in an infinite fluid otherwise at rest are computed
      using a boundary element method, and the trajectories of the two interacting
      bacteria and the stresslet are investigated. The results show that as the two
      bacteria approach each other, they change their orientations considerably in the
      near field. The bacteria always avoided each other; no stable pairwise swimming
      motion was observed in this study. The effects of the hydrodynamic interactions
      between two bacteria on the rheology and diffusivity of a semidilute bacterial
      suspension are discussed.

PMID- 17496015
TI  - External K activation of Kir1.1 depends on the pH gate.
AB  - The inward rectifier Kir1.1 (ROMK) family is gated by both internal pH and
      external K, where the putative pH gate is formed by the convergence of leucine
      side chains, near the inner helical bundle crossing at L160-Kir1.1. However, it
      is unclear whether K activation is mediated at the pH gate or by another gate in
      the permeation path. In this study, we used the whole-cell conductance increase
      during rapid K elevation as a measure of K activation, assuming that activation
      is inherently slower than changes in channel conduction. Results indicate that
      structural disruption of the Kir1.1 bundle-crossing pH gate prevents both
      inactivation by low external K and reactivation by high external K.

PMID- 17496016
TI  - Ab initio protein structure prediction using chunk-TASSER.
AB  - We have developed an ab initio protein structure prediction method called chunk
      TASSER that uses ab initio folded supersecondary structure chunks of a given
      target as well as threading templates for obtaining contact potentials and
      distance restraints. The predicted chunks, selected on the basis of a new
      fragment comparison method, are folded by a fragment insertion method. Full
      length models are built and refined by the TASSER methodology, which searches
      conformational space via parallel hyperbolic Monte Carlo. We employ an optimized
      reduced force field that includes knowledge-based statistical potentials and
      restraints derived from the chunks as well as threading templates. The method is
      tested on a dataset of 425 hard target proteins < or =250 amino acids in length.
      The average TM-scores of the best of top five models per target are 0.266, 0.336,
      and 0.362 by the threading algorithm SP(3), original TASSER and chunk-TASSER,
      respectively. For a subset of 80 proteins with predicted alpha-helix content > or
      =50%, these averages are 0.284, 0.356, and 0.403, respectively. The percentages
      of proteins with the best of top five models having TM-score > or =0.4 (a
      statistically significant threshold for structural similarity) are 3.76, 20.94,
      and 28.94% by SP(3), TASSER, and chunk-TASSER, respectively, overall, while for
      the subset of 80 predominantly helical proteins, these percentages are 2.50,
      23.75, and 41.25%. Thus, chunk-TASSER shows a significant improvement over TASSER
      for modeling hard targets where no good template can be identified. We also
      tested chunk-TASSER on 21 medium/hard targets <200 amino-acids-long from CASP7.
      Chunk-TASSER is approximately 11% (10%) better than TASSER for the total TM-score
      of the first (best of top five) models. Chunk-TASSER is fully automated and can
      be used in proteome scale protein structure prediction.

PMID- 17496017
TI  - Nano-scale dynamic recognition imaging on vascular endothelial cells.
AB  - Combination of high-resolution atomic force microscope topography imaging with
      single molecule force spectroscopy provides a unique possibility for the
      detection of specific molecular recognition events. The identification and
      localization of specific receptor binding sites on complex heterogeneous
      biosurfaces such as cells and membranes are of particular interest in this
      context. Here simultaneous topography and recognition imaging (TREC) was applied
      to gently fixed microvascular endothelial cells from mouse myocardium (MyEnd) to
      identify binding sites of vascular endothelial (VE)-cadherin, known to play a
      crucial role in calcium-dependent, homophilic cell-to-cell adhesion. TREC images
      were acquired with magnetically oscillating atomic-force microscope tips
      functionalized with a recombinant VE-cadherin-Fc cis-dimer. The recognition
      images revealed single molecular binding sites and prominent, irregularly shaped
      dark spots (domains) with sizes ranging from 10 to 100 nm. These domains arose
      from a decrease of the oscillation amplitude during specific binding between
      active VE-cadherin cis-dimers. The VE-cadherin clusters were subsequently
      assigned to topography features. TREC represents an exquisite method to quickly
      obtain the local distribution of receptors on cellular surface with an
      unprecedented lateral resolution of 5 nm.

PMID- 17496018
TI  - Proton transfer in water wires in proteins: modulation by local constraint and
      polarity in gramicidin a channels.
AB  - The transfer of protons in membrane proteins is an essential phenomenon in
      biology. However, the basic rules by which H(+) transfer occurs in water wires
      inside proteins are not well characterized. In particular, the effects of
      specific atoms and small groups of atoms on the rate of H(+) transfer in water
      wires are not known. In this study, new covalently linked gramicidin-A (gA)
      peptides were synthesized, and the effects of specific atoms and peptide
      constraints on the rate of H(+) transfer were measured in single molecules. The N
      termini of two gA peptides were linked to various molecules: S,S-cyclopentane
      diacid, R,R-cyclopentane diacid, and succinic acid. Single-channel proton
      conductances (g(H)) were measured at various proton concentrations ([H(+)]) and
      compared to previous measurements obtained in the S,S- and R,R-dioxolane-linked
      as well as in native gA channels. Replacing the S,S-dioxolane by an S,S
      cyclopentane had no effects on the g(H)-[H(+)] relationships, suggesting that the
      constrained and continuous transition between the two gA peptides via these S,S
      linkers is ultimately responsible for the two- to fourfold increase in g(H)
      relative to native gA channels. It is likely that constraining a continuous
      transition between the two gA peptides enhances the rate of H(+) transfer in
      water wires by decreasing the number of water wire configurations that do not
      transfer H(+) at higher rates as in native gA channels (a decrease in the
      activation entropy of the system). On the other hand, g(H) values in the R,R
      cyclopentane are considerably larger than those in R,R-dioxolane-linked gA
      channels. One explanation would be that the electrostatic interactions between
      the oxygens in the dioxolane and adjacent carbonyls in the R,R-dioxolane-linked
      gA channel attenuate the rate of H(+) transfer in the middle of the pore.
      Interestingly, g(H)-[H(+)] relationships in the R,R-cyclopentane-linked gA
      channel are quite similar to those in native gA channels. g(H) values in succinyl
      linked gA channels display a wide distribution of values that is well represented
      by a bigaussian. The larger peaks of these distributions are similar to g(H)
      values measured in native gA channel. This observation is also consistent with
      the notion that constraining the transition between the two beta-helical gA
      peptides enhances the rate of H(+) transfer in water wires by decreasing the
      activation entropy of the system.

PMID- 17496019
TI  - Formation of ceramide/sphingomyelin gel domains in the presence of an unsaturated
      phospholipid: a quantitative multiprobe approach.
AB  - To better understand how ceramide modulates the biophysical properties of the
      membrane, the interactions between palmitoyl-ceramide (PCer) and palmitoyl
      sphingomyelin (PSM) were studied in the presence of the fluid phospholipid
      palmitoyl-oleoyl-phosphatidylcholine (POPC) in membrane model systems. The use of
      two fluorescent membrane probes distinctly sensitive to lipid phases allowed a
      thorough biophysical characterization of the ternary system. In these mixtures,
      PCer recruits POPC and PSM in the fluid phase to form extremely ordered and
      compact gel domains. Gel domain formation by low PCer mol fraction (up to 12 mol
      %) is enhanced by physiological PSM levels (approximately 20-30 mol % total
      lipid). For higher PSM content, a three-phase situation, consisting of fluid
      (POPC-rich)/gel (PSM-rich)/gel (PCer-rich) coexistence, is clearly shown. To
      determine the fraction of each phase a quantitative method was developed. This
      allowed establishing the complete ternary phase diagram, which helps to predict
      PCer-rich gel domain formation and explains its enhancement through PSM/PCer
      interactions.

PMID- 17496020
TI  - Stability and robustness of an organelle number control system: modeling and
      measuring homeostatic regulation of centriole abundance.
AB  - Control of organelle abundance is a fundamental unsolved problem in cell biology.
      Mechanisms for number control have been proposed in which organelle assembly is
      actively increased or decreased to compensate for deviations from a set-point,
      but such phenomena have not been experimentally verified. In this report we
      examine the control of centriole copy number. We develop a simple scheme to
      represent organelle inheritance as a first-order Markov process and describe two
      figures of merit based on entropy and convergence times that can be used to
      evaluate performance of organelle number control systems. Using this approach we
      show that segregation of centrioles by the mitotic spindle can shape the
      specificity of the steady-state centriole number distribution but is neither
      necessary nor sufficient for stable restoration of centriole number following
      perturbations. We then present experimental evidence that living cells can
      restore correct centriole copy number following transient perturbation, revealing
      a homeostatic control system. We present evidence that correction occurs at the
      level of single cell divisions, does not require association of centrioles with
      the mitotic spindle, and involves modulation of centriole assembly as a function
      of centriole number during S-phase. Combining our experimental and modeling
      results, we identify two processes required for error correction, de novo
      assembly and number-limiting, and show that both processes contribute to robust
      and stable homeostatic control of centriole number, yielding a system capable of
      suppressing biological noise at the level of organelle abundance.

PMID- 17496021
TI  - Specific adsorption of osteopontin and synthetic polypeptides to calcium oxalate
      monohydrate crystals.
AB  - Protein-crystal interactions are known to be important in biomineralization. To
      study the physicochemical basis of such interactions, we have developed a
      technique that combines confocal microscopy of crystals with fluorescence imaging
      of proteins. In this study, osteopontin (OPN), a protein abundant in urine, was
      labeled with the fluorescent dye AlexaFluor-488 and added to crystals of calcium
      oxalate monohydrate (COM), the major constituent of kidney stones. In five to
      seven optical sections along the z axis, scanning confocal microscopy was used to
      visualize COM crystals and fluorescence imaging to map OPN adsorbed to the
      crystals. To quantify the relative adsorption to different crystal faces,
      fluorescence intensity was measured around the perimeter of the crystal in
      several sections. Using this method, it was shown that OPN adsorbs with high
      specificity to the edges between {100} and {121} faces of COM and much less so to
      {100}, {121}, or {010} faces. By contrast, poly-L-aspartic acid adsorbs
      preferentially to {121} faces, whereas poly-L-glutamic acid adsorbs to all faces
      approximately equally. Growth of COM in the presence of rat bone OPN results in
      dumbbell-shaped crystals. We hypothesize that the edge-specific adsorption of OPN
      may be responsible for the dumbbell morphology of COM crystals found in human
      urine.

PMID- 17496022
TI  - Two-state model of acto-myosin attachment-detachment predicts C-process of
      sinusoidal analysis.
AB  - The force response of activated striated muscle to length perturbations includes
      the so-called C-process, which has been considered the frequency domain
      representation of the fast single-exponential force decay after a length step
      (phases 1 and 2). The underlying molecular mechanisms of this phenomenon,
      however, are still the subject of various hypotheses. In this study, we derived
      analytical expressions and created a corresponding computer model to describe the
      consequences of independent acto-myosin cross-bridges characterized solely by 1),
      intermittent periods of attachment (t(att)) and detachment (t(det)), whose values
      are stochastically governed by independent probability density functions; and 2),
      a finite Hookian stiffness (k(stiff)) effective only during periods of
      attachment. The computer-simulated force response of 20,000 (N) cross-bridges
      making up a half-sarcomere (F(hs)(t)) to sinusoidal length perturbations
      (L(hs)(t)) was predicted by the analytical expression in the frequency domain,
      (F(hs)(omega)/L(hs)(omega))=(t(att)/t(cycle))Nk(stiff)(iomega/(t(att)(
      1)+iomega)), where t(att) = mean value of t(att), t(cycle) = mean value of t(att)
      + t(det), k(stiff) = mean stiffness, and omega = 2pi x frequency of perturbation.
      The simulated force response due to a length step (L(hs)) was furthermore
      predicted by the analytical expression in the time domain,
      F(hs)(t)=(t(att)/t(cycle))Nk(stiff)L(hs)e(-t/t(att)). The forms of these
      analytically derived expressions are consistent with expressions historically
      used to describe these specific characteristics of a force response and suggest
      that the cycling of acto-myosin cross-bridges and their associated stiffnesses
      are responsible for the C-process and for phases 1 and 2. The rate constant 2pic,
      i.e., the frequency parameter of the historically defined C-process, is shown
      here to be equal to t(att)(-1). Experimental results from activated cardiac
      muscle examined at different temperatures and containing predominately alpha- or
      beta-myosin heavy chain isoforms were found to be consistent with the above
      interpretation.

PMID- 17496023
TI  - Nav channel mechanosensitivity: activation and inactivation accelerate reversibly
      with stretch.
AB  - Voltage-gated sodium channels (Nav) are modulated by many bilayer mechanical
      amphiphiles, but whether, like other voltage-gated channels (Kv, HCN, Cav), they
      respond to physical bilayer deformations is unknown. We expressed human heart
      Nav1.5 pore alpha-subunit in oocytes (where, unlike alphaNav1.4, alphaNav1.5
      exhibits normal kinetics) and measured small macroscopic currents in cell
      attached patches. Pipette pressure was used to reversibly stretch the membrane
      for comparison of I(Na)(t) before, during, and after stretch. At all voltages,
      and in a dose-dependent fashion, stretch accelerated the I(Na)(t) time course.
      The sign of membrane curvature was not relevant. Typical stretch stimuli
      reversibly accelerated both activation and inactivation by approximately 1.4
      fold; normalization of peak I(Na)(t) followed by temporal scaling ( approximately
      1.30- to 1.85-fold) resulted in full overlap of the stretch/no-stretch traces.
      Evidently the rate-limiting outward voltage sensor motion in the Nav1.5
      activation path (as in Kv1) accelerated with stretch. Stretch-accelerated
      inactivation occurred even with activation saturated, so an independently stretch
      modulated inactivation transition is also a possibility. Since Nav1.5 channel
      stretch modulation was both reliable and reversible, and required stretch stimuli
      no more intense than what typically activates putative mechanotransducer channels
      (e.g., stretch-activated TRPC1-based currents), Nav channels join the ranks of
      putative mechanotransducers. It is noteworthy that at voltages near the
      activation threshold, moderate stretch increased the peak I(Na) amplitude
      approximately 1.5-fold. It will be important to determine whether stretch
      modulated Nav current contributes to cardiac arrhythmias, to mechanosensory
      responses in interstitial cells of Cajal, to touch receptor responses, and to
      neuropathic (i.e., hypermechanosensitive) and/or normal pain reception.

PMID- 17496024
TI  - Formation and reversible dissociation of coiled coil of peptide to the C-terminus
      of the HSV B5 protein: a time-resolved spectroscopic analysis.
AB  - An understanding of the molecular mechanisms of the newly characterized herpes
      simplex virus (HSV) B5 protein is important to further elucidate the HSV cell
      entry and infection. The synthetic peptide of B5 (wtB5) was functionalized with
      the nonlinear optical chromophore cascade yellow and its molecular dynamics was
      probed at physiological and endosomal pH (pH 7.4 and 5.5, respectively). Steady
      state CD spectroscopy was utilized to characterize the peptides at different pH.
      These spectra showed structural changes in the peptide with time measured over
      several days. Nonlinear optical measurements were carried out to probe the
      interactions and local environment of the labeled peptide, and the increase in
      the two-photon cross section of this system suggests an increase in chromophore
      peptide interactions. Time-resolved fluorescence upconversion measurements
      reflected changes in the hydrophilic and hydrophobic local environments of the
      labeled peptide-chromophore system. Ultrafast depolarization measurements gave
      rotational correlation times indicative of a reversible change in the size of the
      peptide. The time-resolved results provide compelling evidence of a reversible
      dissociation of the coiled coils of the wtB5 peptide. This process was found to
      be pH-insensitive. The data from this unique combination of techniques provide an
      initial step to understanding the molecular dynamics of B5 and a framework for
      the development of novel imaging methods based on two-photon emission, as well as
      new therapeutics for HSV.

PMID- 17496025
TI  - Interactions of cationic-hydrophobic peptides with lipid bilayers: a Monte Carlo
      simulation method.
AB  - We present a computational model of the interaction between hydrophobic cations,
      such as the antimicrobial peptide, Magainin2, and membranes that include anionic
      lipids. The peptide's amino acids were represented as two interaction sites: one
      corresponds to the backbone alpha-carbon and the other to the side chain. The
      membrane was represented as a hydrophobic profile, and its anionic nature was
      represented by a surface of smeared charges. Thus, the Coulombic interactions
      between the peptide and the membrane were calculated using the Gouy-Chapman
      theory that describes the electrostatic potential in the aqueous phase near the
      membrane. Peptide conformations and locations near the membrane, and changes in
      the membrane width, were sampled at random, using the Metropolis criterion,
      taking into account the underlying energetics. Simulations of the interactions of
      heptalysine and the hydrophobic-cationic peptide, Magainin2, with acidic
      membranes were used to calibrate the model. The calibrated model reproduced
      structural data and the membrane-association free energies that were measured
      also for other basic and hydrophobic-cationic peptides. Interestingly,
      amphipathic peptides, such as Magainin2, were found to adopt two main membrane
      associated states. In the first, the peptide resided mostly outside the polar
      headgroups region. In the second, which was energetically more favorable, the
      peptide assumed an amphipathic-helix conformation, where its hydrophobic face was
      immersed in the hydrocarbon region of the membrane and the charged residues were
      in contact with the surface of smeared charges. This dual behavior provides a
      molecular interpretation of the available experimental data.

PMID- 17496026
TI  - Effects of serine-to-cysteine mutations on beta-lactamase folding.
AB  - B. licheniformis exo-small beta-lactamase (ESBL) has two nonsequential domains
      and a complex architecture. We replaced ESBL serine residues 126 and 265 with
      cysteine to probe the conformation of buried regions in each domain.
      Spectroscopic, hydrodynamic, and chemical methods revealed that the mutations do
      not alter the native fold but distinctly change stability (S-126C > wild-type > S
      126/265C > S-265C ESBL) and the features of partially folded states. The observed
      wild-type ESBL equilibrium intermediate has decreased fluorescence but full
      secondary structure. S-126C ESBL intermediate has the fluorescence of the
      unfolded state, no thiol reactivity, and partial secondary structure. S-265C and
      S-126/265C ESBL populate intermediate states unfolded by fluorescence and thiol
      reactivity but with full secondary structure. Mass analysis of S-126/265C ESBL in
      the partially folded state proved that both thiol groups become exposed
      simultaneously. None of the intermediates is compatible with sequential domain
      unfolding. Molecular dynamics simulation suggests that the stabilizing effect of
      the S-126C substitution is due to optimization of van der Waals interactions and
      packing. On the other hand, destabilization induced by the S-265C mutation
      results from alteration of the hydrogen-bond network. The results illustrate the
      large impact that seemingly conservative serine-to-cysteine changes can have on
      the energy landscape of proteins.

PMID- 17496027
TI  - Development of linear irreversible thermodynamic model for oxidation reduction
      potential in environmental microbial system.
AB  - Nernst equation has been directly used to formulate the oxidation reduction
      potential (ORP) of reversible thermodynamic conditions but applied to
      irreversible conditions after several assumptions and/or modifications. However,
      the assumptions are sometimes inappropriate in the quantification of ORP in
      nonequilibrium system. We propose a linear nonequilibrium thermodynamic model,
      called microbial related reduction and oxidation reaction (MIRROR Model No. 1)
      for the interpretation of ORP in biological process. The ORP was related to the
      affinities of catabolism and anabolism. The energy expenditure of catabolism and
      anabolism was directly proportional to overpotential (eta), straight coefficient
      of electrode (L(EE)), and degree of coupling between catabolism and ORP
      electrode, respectively. Finally, the limitations of MIRROR Model No. 1 were
      discussed for expanding the applicability of the model.

PMID- 17496029
TI  - Solution conformation of the His-47 to Ala-47 mutant of Pseudomonas stutzeri
      ZoBell ferrocytochrome c-551.
AB  - In the cytochrome c-551 family, the heme 17-propionate caboxylate group is always
      hydrogen bonded to an invariant Trp-56 and conserved residues (His and Arg
      mainly, Lys occasionally) at position 47. The mutation of His-47 to Ala-47 for
      Pseudomas stutzeri ZoBell cytochrome c-551 removes this otherwise invariant
      hydrogen bond. The solution structure of ferrous H47A has been solved based on
      NMR-derived constraints. Results indicate that the mutant has very similar main
      chain folding compared to wild-type. However, less efficient packing of residues
      in the mutant surrounding the heme propionates leads to more solvent exposure for
      both propionate groups, which may account for decreased stability of the mutant.
      The mutant has a reduction potential different from wild-type, and furthermore,
      the pH dependence of this potential is not the same as for wild-type. The
      structure of the mutant suggests that these changes are related to the loss of
      the residue-47 propionate hydrogen bond and the loss of charge on the side chain
      of residue 47.

PMID- 17496028
TI  - Kinetics of oligonucleotide hybridization to DNA probe arrays on high-capacity
      porous silica substrates.
AB  - We have investigated the kinetics of DNA hybridization to oligonucleotide arrays
      on high-capacity porous silica films that were deposited by two techniques. Films
      created by spin coating pure colloidal silica suspensions onto a substrate had
      pores of approximately 23 nm, relatively low porosity (35%), and a surface area
      of 17 times flat glass (for a 0.3-microm film). In the second method, latex
      particles were codeposited with the silica by spin coating and then pyrolyzed,
      which resulted in larger pores (36 nm), higher porosity (65%), and higher surface
      area (26 times flat glass for a 0.3-microm film). As a result of these favorable
      properties, the templated silica hybridized more quickly and reached a higher
      adsorbed target density (11 vs. 8 times flat glass at 22 degrees C) than the pure
      silica. Adsorption of DNA onto the high-capacity films is controlled by
      traditional adsorption and desorption coefficients, as well as by morphology
      factors and transient binding interactions between the target and the probes. To
      describe these effects, we have developed a model based on the analogy to
      diffusion of a reactant in a porous catalyst. Adsorption values (k(a), k(d), and
      K) measured on planar arrays for the same probe/target system provide the
      parameters for the model and also provide an internally consistent comparison for
      the stability of the transient complexes. The interpretation of the model takes
      into account factors not previously considered for hybridization in three
      dimensional films, including the potential effects of heterogeneous probe
      populations, partial probe/target complexes during diffusion, and non-1:1 binding
      structures. The transient complexes are much less stable than full duplexes
      (binding constants for full duplexes higher by three orders of magnitude or
      more), which may be a result of the unique probe density and distribution that is
      characteristic of the photolithographically patterned arrays. The behavior at 22
      degrees C is described well by the predictive equations for morphology, whereas
      the behavior at 45 degrees C deviates from expectations and suggests that more
      complex phenomena may be occurring in that temperature regime.

PMID- 17496030
TI  - Gold-nanoparticle-assisted laser perturbation of chromatin assembly reveals
      unusual aspects of nuclear architecture within living cells.
AB  - Chromatin organization within the nucleus is a vital regulator of genome
      function, yet its mechanical coupling to the nuclear architecture has remained
      elusive. To directly investigate this coupling, we locally modulated chromatin
      structure in living cells using nanoparticle-based laser perturbation. Unusual
      differences in the response of the cell nucleus were observed depending on the
      nuclear region that was perturbed--the heterochromatin, the euchromatin, and the
      nuclear envelope. This response varied under different conditions of cellular
      perturbations such as ATP depletion, apoptosis, and inhibition of histone
      deacetylases. Our studies implicate heterochromatin organization in imparting
      mechanical stability to the cell nucleus and suggest that nuclear size and shape
      are the result of interplay between nuclear and cytoplasmic anchors.

PMID- 17496031
TI  - Role of a conserved salt bridge between the PAS core and the N-terminal domain in
      the activation of the photoreceptor photoactive yellow protein.
AB  - The effect of ionic strength on the conformational equilibrium between the I(2)
      intermediate and the signaling state I(2)' of the photoreceptor PYP and on the
      rate of recovery to the dark state were investigated by time-resolved absorption
      and fluorescence spectroscopy. With increasing salt concentration up to
      approximately 600 mM, the recovery rate k(3) decreases and the I(2)/I(2)'
      equilibrium (K) shifts in the direction of I(2)'. At higher ionic strength both
      effects reverse. Experiments with mono-(KCl, NaBr) and divalent (MgCl(2),
      MgSO(4)) salts show that the low salt effect depends on the ionic strength and
      not on the cation or anion species. These observations can be described over the
      entire ionic strength range by considering the activity coefficients of an
      interdomain salt bridge. At low ionic strength the activity coefficient decreases
      due to counterion screening whereas at high ionic strength binding of water by
      the salt leads to an increase in the activity coefficient. From the initial
      slopes of the plots of log k(3) and log K versus the square root of the ionic
      strength, the product of the charges of the interacting groups was found to be 
      1.3 +/- 0.2, suggesting a monovalent ion pair. The conserved salt bridge K110/E12
      connecting the beta-sheet of the PAS core and the N-terminal domain is a prime
      candidate for this ion pair. To test this hypothesis, the mutants K110A and E12A
      were prepared. In K110A the salt dependence of the I(2)/I(2)' equilibrium was
      eliminated and of the recovery rate was greatly reduced below approximately 600
      mM. Moreover, at low salt the recovery rate was six times slower than in wild
      type. In E12A significant salt dependence remained, which is attributed to the
      formation of a novel salt bridge between K110 and E9. At high salt reversal
      occurs in both mutants suggesting that salting out stabilizes the more compact
      I(2) structure. However, chaotropic anions like SCN shift the I(2)/I(2)'
      equilibrium toward the partially unfolded I(2)' form. The salt linkage K110/E12
      stabilizes the photoreceptor in the inactive state in the dark and is broken in
      the light-induced formation of the signaling state, allowing the N-terminal
      domain to detach from the beta-scaffold PAS core.

PMID- 17496032
TI  - Effect of calcium concentration on the structure of casein micelles in thin
      films.
AB  - The structure of thin casein films prepared with spin-coating is investigated as
      a function of the calcium concentration. Grazing incidence small-angle x-ray
      scattering and atomic force microscopy are used to probe the micelle structure.
      For comparison, the corresponding casein solutions are investigated with dynamic
      light-scattering experiments. In the thin films with added calcium three types of
      casein structures, aggregates, micelles, and mini-micelles, are observed in
      coexistence with atomic force microscopy and grazing incidence small-angle x-ray
      scattering. With increasing calcium concentration, the size of the aggregates
      strongly increases, while the size of micelles slightly decreases and the size of
      the mini-micelles increases. This effect is explained in the framework of the
      particle-stabilizing properties of the hairy layer of kappa-casein surrounding
      the casein micelles.

PMID- 17496033
TI  - Analyzing forced unfolding of protein tandems by ordered variates, 1: Independent
      unfolding times.
AB  - Most of the mechanically active proteins are organized into tandems of identical
      repeats, (D)N, or heterogeneous tandems, D1-D2-...-DN. In current atomic force
      microscopy experiments, conformational transitions of protein tandems can be
      accessed by employing constant stretching force f (force-clamp) and by analyzing
      the recorded unfolding times of individual domains. Analysis of unfolding data
      for homogeneous tandems relies on the assumption that unfolding times are
      independent and identically distributed, and involves inference of the (parent)
      probability density of unfolding times from the histogram of the combined
      unfolding times. This procedure cannot be used to describe tandems characterized
      by interdomain interactions, or heteregoneous tandems. In this article, we
      introduce an alternative approach that is based on recognizing that the observed
      data are ordered, i.e., first, second, third, etc., unfolding times. The approach
      is exemplified through the analysis of unfolding times for a computer model of
      the homogeneous and heterogeneous tandems, subjected to constant force. We show
      that, in the experimentally accessible range of stretching forces, the
      independent and identically distributed assumption may not hold. Specifically,
      the uncorrelated unfolding transitions of individual domains at lower force may
      become correlated (dependent) at elevated force levels. The proposed formalism
      can be used in atomic force microscopy experiments to infer the unfolding time
      distributions of individual domains from experimental histograms of ordered
      unfolding times, and it can be extended to analyzing protein tandems that exhibit
      interdomain interactions.

PMID- 17496034
TI  - Oligomerization of the EGF receptor investigated by live cell fluorescence
      intensity distribution analysis.
AB  - Recent evidence suggests that the EGF receptor oligomerizes or clusters in cells
      even in the absence of agonist ligand. To assess the status of EGF receptors in
      live cells, an EGF receptor fused to eGFP was stably expressed in CHO cells and
      studied using fluorescence correlation spectroscopy and fluorescent brightness
      analysis. By modifying FIDA for use in a two-dimensional system with quantal
      brightnesses, a method was developed to quantify the degree of clustering of the
      receptors on the cell surface. The analysis demonstrates that under physiological
      conditions, the EGF receptor exists in a complex equilibrium involving single
      molecules and clusters of two or more receptors. Acute depletion of cellular
      cholesterol enhanced EGF receptor clustering whereas cholesterol loading
      decreased receptor clustering, indicating that receptor aggregation is sensitive
      to the lipid composition of the membrane.

PMID- 17496035
TI  - Computational prediction of atomic structures of helical membrane proteins aided
      by EM maps.
AB  - Integral membrane proteins pose a major challenge for protein-structure
      prediction because only approximately 100 high-resolution structures are
      available currently, thereby impeding the development of rules or empirical
      potentials to predict the packing of transmembrane alpha-helices. However, when
      an intermediate-resolution electron microscopy (EM) map is available, it can be
      used to provide restraints which, in combination with a suitable computational
      protocol, make structure prediction feasible. In this work we present such a
      protocol, which proceeds in three stages: 1), generation of an ensemble of alpha
      helices by flexible fitting into each of the density rods in the low-resolution
      EM map, spanning a range of rotational angles around the main helical axes and
      translational shifts along the density rods; 2), fast optimization of side chains
      and scoring of the resulting conformations; and 3), refinement of the lowest
      scoring conformations with internal coordinate mechanics, by optimizing the van
      der Waals, electrostatics, hydrogen bonding, torsional, and solvation energy
      contributions. In addition, our method implements a penalty term through a so
      called tethering map, derived from the EM map, which restrains the positions of
      the alpha-helices. The protocol was validated on three test cases: GpA, KcsA, and
      MscL.

PMID- 17496036
TI  - Mechanical properties of inner-arm dynein-f (dynein I1) studied with in vitro
      motility assays.
AB  - Inner-arm dynein-f of Chlamydomonas flagella is a heterodimeric dynein. We
      performed conventional in vitro motility assays showing that dynein-f
      translocates microtubules at the comparatively low velocity of approximately 1.2
      microm/s. From the dependence of velocity upon the surface density of dynein-f,
      we estimate its duty ratio to be 0.6-0.7. The relation between microtubule
      landing rate and surface density of dynein-f are well fitted by the first-power
      dependence, as expected for a processive motor. At low dynein densities,
      progressing microtubules rotate erratically about a fixed point on the surface,
      at which a single dynein-f molecule is presumably located. We conclude that
      dynein-f has high processivity. In an axoneme, however, slow and processive
      dynein-f could impede microtubule sliding driven by other fast dyneins (e.g.,
      dynein-c). To obtain insight into the in vivo roles of dynein-f, we measured the
      sliding velocity of microtubules driven by a mixture of dyneins -c and -f at
      various mixing ratios. The velocity is modulated as a function of the ratio of
      dynein-f in the mixture. This modulation suggests that dynein-f acts as a load in
      the axoneme, but force pushing dynein-f molecules forward seems to accelerate
      their dissociation from microtubules.

PMID- 17496037
TI  - Functional modularity of the beta-subunit of voltage-gated Ca2+ channels.
AB  - The beta-subunit of voltage-gated Ca(2+) channels plays a dual role in
      chaperoning the channels to the plasma membrane and modulating their gating. It
      contains five distinct modular domains/regions, including the variable N- and C
      terminus, a conserved Src homology 3 (SH3) domain, a conserved guanylate kinase
      (GK) domain, and a connecting variable and flexible HOOK region. Recent
      crystallographic studies revealed a highly conserved interaction between the GK
      domain and alpha interaction domain (AID), the high-affinity binding site in the
      pore-forming alpha(1) subunit. Here we show that the AID-GK domain interaction is
      necessary for beta-subunit-stimulated Ca(2+) channel surface expression and that
      the GK domain alone can carry out this function. We also examined the role of
      each region of all four beta-subunit subfamilies in modulating P/Q-type Ca(2+)
      channel gating and demonstrate that the beta-subunit functions modularly. Our
      results support a model that the conserved AID-GK domain interaction anchors the
      beta-subunit to the alpha(1) subunit, enabling alpha(1)-beta pair-specific low
      affinity interactions involving the N-terminus and the HOOK region, which confer
      on each of the four beta-subunit subfamilies its distinctive modulatory
      properties.

PMID- 17496038
TI  - Perlinhibin, a cysteine-, histidine-, and arginine-rich miniprotein from abalone
      (Haliotis laevigata) nacre, inhibits in vitro calcium carbonate crystallization.
AB  - We have isolated a 4.785 Da protein from the nacreous layer of the sea snail
      Haliotis laevigata (greenlip abalone) shell after demineralization with acetic
      acid. The sequence of 41 amino acids was determined by Edman degradation
      supported by mass spectrometry. The most abundant amino acids were cysteine
      (19.5%), histidine (17%), and arginine (14.6%). The positively charged amino
      acids were almost counterbalanced by negatively charged ones resulting in a
      calculated isoelectric point of 7.86. Atomic-force microscopy studies of the
      interaction of the protein with calcite surfaces in supersaturated calcium
      carbonate solution or calcium chloride solution showed that the protein bound
      specifically to calcite steps, inhibiting further crystal growth at these sites
      in carbonate solution and preventing crystal dissolution when carbonate was
      substituted with chloride. Therefore this protein was named perlinhibin. X-ray
      diffraction investigation of the crystal after atomic-force microscopy growth
      experiments showed that the formation of aragonite was induced on the calcite
      substrate around holes caused by perlinhibin crystal-growth inhibition. The
      strong interaction of the protein with calcium carbonate was also shown by vapor
      diffusion crystallization. In the presence of the protein, the crystal surfaces
      were covered with holes due to protein binding and local inhibition of crystal
      growth. In addition to perlinhibin, we isolated and sequenced a perlinhibin
      related protein, indicating that perlinhibin may be a member of a family of
      closely related proteins.

PMID- 17496039
TI  - Violation of the fluctuation-dissipation theorem in a protein system.
AB  - We report the results of molecular dynamics simulations of the protein myosin
      carried out with an elastic network model. Quenching the system, we observe
      glassy behavior of a density correlation function and a density response function
      that are often investigated in structure glasses and spin glasses. In the
      equilibrium, the fluctuation-response relation, a representative relation of the
      fluctuation-dissipation theorem, holds that the ratio of the density correlation
      function to the density response function is equal to the temperature of the
      environment. We show that, in the quenched system that we study, this relation
      can be violated. In the case that this relation does not hold, this ratio can be
      regarded as an effective temperature. We find that this effective temperature of
      myosin is higher than the temperature of the environment. We discuss the relation
      between this effective temperature and energy transduction that occurs after ATP
      hydrolysis in the myosin molecule.

PMID- 17496040
TI  - Sodium channels: ionic model of slow inactivation and state-dependent drug
      binding.
AB  - Inactivation is a fundamental property of voltage-gated ion channels. Fast
      inactivation of Na(+) channels involves channel block by the III-IV cytoplasmic
      interdomain linker. The mechanisms of nonfast types of inactivation
      (intermediate, slow, and ultraslow) are unclear, although the ionic environment
      and P-loops rearrangement appear to be involved. In this study, we employed a TTX
      based P-loop domain model of a sodium channel and the MCM method to investigate a
      possible role of P-loop rearrangement in the nonfast inactivation. Our modeling
      predicts that Na(+) ions can bind between neighboring domains in the outer
      carboxylates ring EEDD, forming an ordered structure with interdomain contacts
      that stabilize the conducting conformation of the outer pore. In this model, the
      permeant ions can transit between the EEDD ring and the selectivity filter ring
      DEKA, retaining contacts with at least two carboxylates. In the absence of Na(+),
      the electrostatic repulsion between the EEDD carboxylates disrupts the permeable
      configuration. In this Na(+)-deficient model, the region between the EEDD and
      DEKA rings is inaccessible for Na(+) but is accessible for TMA. Taken together,
      these results suggest that Na(+)-saturated models are consistent with
      experimental characteristics of the open channels, whereas Na(+)-deficient models
      are consistent with experimentally defined properties of the slow-inactivated
      channels. Our calculations further predict that binding of LAs to the inner pore
      would depend on whether Na(+) occupies the DEKA ring. In the absence of Na(+) in
      the DEKA ring, the cationic group of lidocaine occurs in the focus of the pore
      helices' macrodipoles and would prevent occupation of the ring by Na(+). Loading
      the DEKA ring with Na(+) results in the electrostatic repulsion with lidocaine.
      Thus, there are antagonistic relations between a cationic ligand bound in the
      inner pore and Na(+) in the DEKA ring.

PMID- 17496041
TI  - Lipid lateral segregation driven by diacyl cyclodextrin interactions at the
      membrane surface.
AB  - Cyclodextrins are hydrophilic molecular cages with a hydrophobic interior
      allowing the inclusion of water-insoluble drugs. Amphiphilic cyclodextrins
      obtained by appending a hydrophobic anchor were designed to improve the cell
      targeting of the drug-containing cavities through their liposome transportation
      in the organism. After insertion in model membranes, they were found to induce a
      lateral phase separation into a pure lipid phase and a fluid cyclodextrin-rich
      phase (L(CD)) with reduced acyl chain order parameters, as observed with a
      derivative containing a cholesterol anchor (M. Roux, R. Auzely-Velty, F. Djedaini
      Pilard, and B. Perly. 2002. Biophysical Journal, 8:813-822). We present another
      class of amphiphilic cyclodextrins obtained by grafting aspartic acid esterified
      by two lauryl chains on the oligosaccharide core via a succinyl spacer. The
      obtained dilauryl-beta-cyclodextrin (betaDLC) was inserted in chain perdeuterated
      dimyristoylphosphatidylcholine (DMPC-d54) membranes and studied by deuterium NMR
      ((2)H-NMR). A laterally segregated mixed phase was found to sequester three times
      more lipids than the cholesteryl derivative (approximately 4-5 lipids per monomer
      of betaDLC), and a quasipure L(CD) phase could be obtained with a 20% molar
      concentration of betaDLC. When cooled below the main fluid-to-gel transition of
      DMPC-d54 the betaDLC-rich phase stays fluid, coexisting with pure lipid in the
      gel state, and exhibits a sharp transition to a gel phase with frozen DMPC acyl
      chains at 12.5 degrees C. No lateral phase separation was observed with partially
      or fully methylated betaDLC, confirming that the stability of the segregated
      L(CD) phase was governed through hydrogen-bond-mediated intermolecular
      interactions between cyclodextrin headgroups at the membrane surface. As opposed
      to native betaDLC, the methylated derivatives were found to strongly increase the
      orientational order of DMPC acyl chains as the temperature reaches the membrane
      fluid-to-gel transition. The results are discussed in relation to the "anomalous
      swelling" of saturated phosphatidylcholine multilamellar membranes known to occur
      in the vicinity of the main fluid-to-gel transition.

PMID- 17496043
TI  - A comparative study on axial coordination and ligand binding in ferric mini
      myoglobin and horse heart myoglobin.
AB  - The absorption and resonance Raman spectra and the azide binding kinetics of
      ferric horse heart myoglobin (Mb) and mini myoglobin (a chemically truncated form
      of horse heart Mb containing residues 32-139) have been compared. The steady
      state spectra show that an additional six-coordinated low-spin form (not present
      in entire horse heart Mb, which is purely six-coordinated high spin) predominates
      in mini Mb. The distal histidine is possibly the sixth ligand in this species.
      The presence of two species corresponds to a kinetic biphasicity for mini Mb that
      is not observed for horse heart Mb. Azide binds to horse heart Mb much more
      slowly than to sperm whale Mb. This difference may result from a sterically
      hindered distal pocket in horse heart Mb. In both cases, the rate constants level
      off at high azide concentrations, implying the existence of a rate-limiting step
      (likely referable to the dissociation of the axial sixth ligand). The faster rate
      constant of mini Mb is similar to that of sperm whale Mb, whereas the slower one
      is similar to that of entire horse heart Mb.

PMID- 17496042
TI  - Hybrid stochastic and deterministic simulations of calcium blips.
AB  - Intracellular calcium release is a prime example for the role of stochastic
      effects in cellular systems. Recent models consist of deterministic reaction
      diffusion equations coupled to stochastic transitions of calcium channels. The
      resulting dynamics is of multiple time and spatial scales, which complicates far
      reaching computer simulations. In this article, we introduce a novel hybrid
      scheme that is especially tailored to accurately trace events with essential
      stochastic variations, while deterministic concentration variables are
      efficiently and accurately traced at the same time. We use finite elements to
      efficiently resolve the extreme spatial gradients of concentration variables
      close to a channel. We describe the algorithmic approach and we demonstrate its
      efficiency compared to conventional methods. Our single-channel model matches
      experimental data and results in intriguing dynamics if calcium is used as charge
      carrier. Random openings of the channel accumulate in bursts of calcium blips
      that may be central for the understanding of cellular calcium dynamics.

PMID- 17496044
TI  - Origin of individuality of two daughter cells during the division process
      examined by the simultaneous measurement of growth and swimming property using an
      on-chip single-cell cultivation system.
AB  - We examined the origin of individuality of two daughter cells born from an
      isolated single Escherichia coli mother cell during its cell division process by
      monitoring the change in its swimming behavior and tumbling frequency using an on
      chip single-cell cultivation system. By keeping the isolated condition of an
      observed single cell, we compared its growth and swimming property within a
      generation and over up to seven generations. It revealed that running speed
      decreased as cell length smoothly increased within each generation, whereas
      tumbling frequency fluctuated among generations. Also found was an extraordinary
      tumbling mode characterized by the prolonged duration of pausing in predivisional
      cells after cell constriction. The observed prolonged pausing may imply the
      coexistence of two distinct control systems in a predivisional cell, indicating
      that individuality of daughter cells emerges after a mother cell initiates
      constriction and before it gets physically separated into two new cell bodies.

PMID- 17496045
TI  - Step length measurement--theory and simulation for tethered bead constant-force
      single molecule assay.
AB  - Linear molecular motors translocate along polymeric tracks using discrete steps.
      The step length is usually measured using constant-force single molecule
      experiments in which the polymer is tethered to a force-clamped microsphere.
      During the enzymatic cycle the motor shortens the tether contour length.
      Experimental conditions influence the achievable step length resolution, and
      ideally experiments should be conducted with high clamp-force using slow motors
      linked to small beads via stiff short tethers. We focus on the limitations that
      the polymer-track flexibility, the thermal motion of the microsphere, and the
      motor kinetics pose for step-length measurement in a typical optical tweezers
      experiment. An expression for the signal/noise ratio in a constant-force, worm
      like chain tethered particle, single-molecule experiment is developed. The
      signal/noise ratio is related to the Fourier transform of the pairwise distance
      distribution, commonly used to determine step length from a time-series. Monte
      Carlo simulations verify the proposed theory for experimental parameter values
      typically encountered with molecular motors (polymerases and helicases)
      translocating along single- or double-stranded nucleic acids. The predictions are
      consistent with recent experimental results for double-stranded DNA tethers. Our
      results map favorable experimental conditions for observing single motor steps on
      various substrates but indicate that principal resolution limits are set by
      thermal fluctuations.

PMID- 17496046
TI  - Solute transport in growth plate cartilage: in vitro and in vivo.
AB  - Bone elongation originates from cartilaginous discs (growth plates) at both ends
      of a growing bone. Here chondrocytes proliferate and subsequently enlarge
      (hypertrophy), laying down a matrix that serves as the scaffolding for subsequent
      bone matrix deposition. Because cartilage is generally avascular, all nutrients,
      oxygen, signaling molecules, and waste must be transported relatively long
      distances through the tissue for it to survive and function. Here we examine the
      transport properties of growth plate cartilage. Ex vivo, fluorescence
      photobleaching recovery methods are used in tissue explants. In vivo, multiphoton
      microscopy is used to image through an intact perichondrium and into the
      cartilage of anesthetized mice. Systemically introduced fluorescent tracers are
      monitored directly as they move from the vasculature into the cartilage. We
      demonstrate the existence of a relatively permissive region at the midplane of
      the growth plate, where chondrocytes transition from late proliferative to early
      hypertrophic stages and where paracrine communication is known to occur between
      chondrocytes and cells in the surrounding perichondrium. Transport in the living
      mouse is also significantly affected by fluid flow from the two chondro-osseus
      junctions, presumably resulting from a pressure difference between the bone
      vasculature and the cartilage.

PMID- 17496047
TI  - Tectorial membrane stiffness gradients.
AB  - The mammalian inner ear processes sound with high sensitivity and fine resolution
      over a wide frequency range. The underlying mechanism for this remarkable ability
      is the "cochlear amplifier", which operates by modifying cochlear micromechanics.
      However, it is largely unknown how the cochlea implements this modification.
      Although gradual improvements in experimental techniques have yielded ever-better
      descriptions of gross basilar membrane vibration, the internal workings of the
      organ of Corti and of the tectorial membrane have resisted exploration. Although
      measurements of cochlear function in mice with a gene mutation for alpha-tectorin
      indicate the tectorial membrane's key role in the mechanoelectrical
      transformation by the inner ear, direct experimental data on the tectorial
      membrane's physical properties are limited, and only a few direct measurements on
      tectorial micromechanics are available. Using the hemicochlea, we are able to
      show that a tectorial membrane stiffness gradient exists along the cochlea,
      similar to that of the basilar membrane. In artificial perilymph (but with low
      calcium), the transversal and radial driving point stiffnesses change at a rate
      of -4.0 dB/mm and -4.9 dB/mm, respectively, along the length of the cochlear
      spiral. In artificial endolymph, the stiffness gradient for the transversal
      component was -3.4 dB/mm. Combined with the changes in tectorial membrane
      dimensions from base to apex, the radial stiffness changes would be able to
      provide a second frequency-place map in the cochlea. Young's modulus, which was
      obtained from measurements performed in the transversal direction, decreased by 
      2.6 dB/mm from base to apex.

PMID- 17496048
TI  - A molecular dynamics study of slow base flipping in DNA using conformational
      flooding.
AB  - Individual DNA bases are known to be able to flip out of the helical stack,
      providing enzymes with access to the genetic information otherwise hidden inside
      the helix. Consequently, base flipping is a necessary first step to many more
      complex biological processes such as DNA transcription or replication. Much
      remains unknown about this elementary step, despite a wealth of experimental and
      theoretical studies. From the theoretical point of view, the involved timescale
      of milliseconds or longer requires the use of enhanced sampling techniques. In
      contrast to previous theoretical studies employing umbrella sampling along a
      predefined flipping coordinate, this study attempts to induce flipping without
      prior knowledge of the pathway, using information from a molecular dynamics
      simulation of a B-DNA fragment and the conformational flooding method. The
      relevance to base flipping of the principal components of the simulation is
      assayed, and a combination of modes optimally related to the flipping of the base
      through either helical groove is derived for each of the two bases of the central
      guanine-cytosine basepair. By applying an artificial flooding potential along
      these collective coordinates, the flipping mechanism is accelerated to within the
      scope of molecular dynamics simulations. The associated free energy surface is
      found to feature local minima corresponding to partially flipped states,
      particularly relevant to flipping in isolated DNA; further transitions from these
      minima to the fully flipped conformation are accelerated by additional flooding
      potentials. The associated free energy profiles feature similar barrier heights
      for both bases and pathways; the flipped state beyond is a broad and rugged
      attraction basin, only a few kcal/mol higher in energy than the closed
      conformation. This result diverges from previous works but echoes some aspects of
      recent experimental findings, justifying the need for novel approaches to this
      difficult problem: this contribution represents a first step in this direction.
      Important structural factors involved in flipping, both local (sugar-phosphate
      backbone dihedral angles) and global (helical axis bend), are also identified.

PMID- 17496049
TI  - Fluorescence lifetime imaging to detect actomyosin states in mammalian muscle
      sarcomeres.
AB  - We investigated the use of fluorescence lifetime imaging microscopy (FLIM) of a
      fluorescently labeled ATP analog (3'-O-{N-[3-(7-diethylaminocoumarin-3
      carboxamido)propyl]carbamoyl}ATP) to probe in permeabilized muscle fibers the
      changes in the environment of the nucleotide binding pocket caused by interaction
      with actin. Spatial averaging of FLIM data of muscle sarcomeres reduces photon
      noise, permitting detailed analysis of the fluorescence decay profiles. FLIM
      reveals that the lifetime of the nucleotide, in its ADP form because of the low
      concentration of nucleotide present, changes depending on whether the nucleotide
      is free in solution or bound to myosin, and on whether the myosin is bound to
      actin in an actomyosin complex. Characterization of the fluorescence decays by a
      multiexponential function allowed us to resolve the lifetimes and amplitudes of
      each of these populations, namely, the fluorophore bound to myosin, bound to
      actin, in an actomyosin complex, and free in the filament lattice. This novel
      application of FLIM to muscle fibers shows that with spatial averaging, detailed
      information about the nature of nucleotide complexes can be derived.

PMID- 17496050
TI  - Effects of monovalent anions of the hofmeister series on DPPC lipid bilayers Part
      II: modeling the perpendicular and lateral equation-of-state.
AB  - The effects of Hofmeister anions on the perpendicular and lateral equation-of
      state (EOS) of the dipalmitoylphosphatidylcholine lamellar phase discussed in the
      companion article are here examined using appropriate free energy models for the
      intra- and interbilayer interactions. Minimizing the free energy with respect to
      the two basic geometrical parameters of the lamellar phase, which are the
      interbilayer water thickness, d(w), and the lipid headgroup area, a(L), provides
      the perpendicular (osmotic pressure balance) and lateral EOS. Standard models
      were used for the hydration, undulation, and Van der Waals attractive force
      between the bilayers in the presence of electrolytes whereas two alternative
      treatments of electrostatic interactions were used to obtain "binding" or
      "partitioning" constants of anions to the lipid bilayers both in the absence and
      in the presence of sodium binding. The computed binding constants depend on anion
      type and follow the Hofmeister series, but were found to increase with
      electrolyte concentration, implying that the local binding approximation cannot
      fit bilayer repulsion data. The partitioning model was also found inadequate at
      high electrolyte concentrations. The fitting attempts revealed two additional
      features worthy of future investigation. First, at maximum swelling in the
      presence of electrolytes the osmotic pressure of the bilayer system cannot be set
      equal to zero. Second, at high salt concentrations an additional repulsion
      appears to come into effect in the presence of strongly adsorbing anions such as
      I(-) or SCN(-). Both these phenomena may reflect an inconsistent treatment of the
      ion-surface interactions, which have an impact on the osmotic pressure.
      Alternatively, they may arise from bulk solution nonidealities that cannot be
      handled by the classical Poisson-Boltzmann formalism. The inability of current
      models to explain the "lateral" EOS by fitting the area per lipid headgroup as a
      function of salt type and concentration shows that current understanding of
      phospholipid-ion interactions is still very incomplete.

PMID- 17496051
TI  - Effects of monovalent anions of the hofmeister series on DPPC lipid bilayers Part
      I: swelling and in-plane equations of state.
AB  - Aiming to improve understanding of the mechanisms behind specific anion effects
      in biological systems we have studied the effects of sodium salts of simple
      monovalent anions belonging to the Hofmeister series on the bilayers of the
      zwitterionic lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine using small-angle
      x-ray scattering and the osmotic stress technique. NaCl, NaBr, NaNO(3), NaI, and
      NaSCN were used in this investigation. The electrolytes were found to swell the
      bilayers and to increase the area per lipid headgroup at each value of the
      osmotic pressure, suggesting the association of anions with the bilayer-lipid
      interfaces. The effects follow the Hofmeister series with SCN(-) inducing the
      most pronounced changes. "Ion competition" experiments with mixed NaI/NaCl
      solutions at total salinity 0.1 and 0.5 M revealed that the effect of ions on the
      lipid equation-of-state is roughly linear at low concentrations, but strongly
      nonlinear at high concentrations. The experimental results are fitted in a
      companion article to provide "binding" or "partitioning" constants of anions in
      the lipid bilayers.

PMID- 17496053
TI  - Chlamydia trachomatis infection, Fallopian tube damage and a mannose-binding
      lectin codon 54 gene polymorphism.
AB  - BACKGROUND: Mannose-binding lectin (MBL), a component of the innate immune
      system, provides a first-line defense against invading microorganisms.
      Polymorphisms in the MBL gene have been associated with increased risk of
      infection. Chlamydia trachomatis genital tract infections are a major cause of
      Fallopian tube occlusion. Our objective was to test whether an MBL codon 54
      polymorphism might contribute to development of C. trachomatis-associated tubal
      damage. METHODS: In a case-control study, 97 women with occluded and 104 women
      with patent Fallopian tubes were tested for a history of chlamydial infection by
      serology and for their MBL codon 54 genotype by PCR and restriction fragment
      length polymorphism analysis. Clinical data were blinded to those performing all
      laboratory analyses. RESULTS: Women with tubal occlusion who also had a positive
      chlamydial serology had the highest rate of variant MBL B allele carriage
      (P<0.001). Among women who were chlamydial antibody negative, allele B carriage
      was also more frequent in those with blocked, as opposed to patent, Fallopian
      tubes (P<0.01). CONCLUSIONS: Wild-type allele A homozygosity is protective
      against, while carriage of the variant allele B is a risk factor for, Fallopian
      tube occlusion in women who are seropositive or seronegative for C. trachomatis.

PMID- 17496052
TI  - Secondary and tertiary structure elasticity of titin Z1Z2 and a titin chain
      model.
AB  - The giant protein titin, which is responsible for passive elasticity in muscle
      fibers, is built from approximately 300 regular immunoglobulin-like (Ig) domains
      and FN-III repeats. While the soft elasticity derived from its entropic regions,
      as well as the stiff mechanical resistance derived from the unfolding of the
      secondary structure elements of Ig- and FN-III domains have been studied
      extensively, less is known about the mechanical elasticity stemming from the
      orientation of neighboring domains relative to each other. Here we address the
      dynamics and energetics of interdomain arrangement of two adjacent Ig-domains of
      titin, Z1, and Z2, using molecular dynamics (MD) simulations. The simulations
      reveal conformational flexibility, due to the domain-domain geometry, that lends
      an intermediate force elasticity to titin. We employ adaptive biasing force MD
      simulations to calculate the energy required to bend the Z1Z2 tandem open to
      identify energetically feasible interdomain arrangements of the Z1 and Z2
      domains. The finding is cast into a stochastic model for Z1Z2 interdomain
      elasticity that is generalized to a multiple domain chain replicating many Z1Z2
      like units and representing a long titin segment. The elastic properties of this
      chain suggest that titin derives so-called tertiary structure elasticity from
      bending and twisting of its domains. Finally, we employ steered molecular
      dynamics simulations to stretch individual Z1 and Z2 domains and characterize the
      so-called secondary structure elasticity of the two domains. Our study suggests
      that titin's overall elastic response at weak force stems from a soft entropic
      spring behavior (not described here), from tertiary structure elasticity with an
      elastic spring constant of approximately 0.001-1 pN/A and, at strong forces, from
      secondary structure elasticity.

PMID- 17496054
TI  - Limited value of morphological assessment at days 1 and 2 to predict blastocyst
      development potential: a prospective study based on 4042 embryos.
AB  - BACKGROUND: Non-invasive and routine developmental markers are available to
      select the most viable embryo; however their respective values in terms of
      blastocyst development potential remain difficult to distinguish. METHODS: During
      this prospective study, the sequential growth of 4042 embryos individually
      cultured from day 1 to day 5/6 was recorded. Pronuclear morphology on day 1, and
      early cleavage, cell number and fragmentation rate on day 2 were evaluated for
      each zygote. Additionally, blastocyst transfers were analysed with regard to
      their implantation ability and early embryo development parameters. RESULTS: Once
      adjusted to each other, each of the four parameters remained related to
      blastocyst development. Early cleavage and cell number on day 2 were the most
      powerful parameters to predict the development of a good morphology blastocyst at
      day 5. Moreover, whereas transfers of a good morphology blastocyst were
      associated with high implantation and live birth rates, parameters of early
      development were not helpful in predicting their implantation ability.
      CONCLUSIONS: The combination of all four parameters allowed the prediction of
      blastocyst development with an area under the receiver operating characteristics
      curve of 0.688, which represents a fairly low prediction of embryo viability.
      Such results indicate that it is necessary to search for additional criteria,
      including the ability of the blastocyst to develop.

PMID- 17496055
TI  - SPP1 polymorphisms associated with HBV clearance and HCC occurrence.
AB  - BACKGROUND: Secreted phosphoprotein-1 (SPP1) is a secreted arginine-glycine
      aspartate (RGD)-containing phosphoprotein. SPP1 is overexpressed in metastatic
      hepatocellular carcinoma (HCC), and therefore could act as both a diagnostic
      marker and a potential therapeutic target for metastatic HCC. We investigated the
      genetic polymorphisms in SPP1 to determine whether it is a potential candidate
      gene for a host genetic study of hepatitis B virus (HBV) clearance and HCC
      occurrence. METHODS: Five genetic variants in SPP1 were genotyped by TaqMan assay
      and the genetic association with HBV clearance and HCC occurrence was analysed.
      RESULTS: Genetic association analysis of SPP1 polymorphisms with an HBV cohort (n
      = 1,069) from the Korean population revealed that the most common haplotype (SPP1
      ht2 [T-T-C-T-A]) was associated with HBV clearance. The frequency of the SPP1-ht2
      bearing genotype in the chronic carrier (CC) group was higher than in the
      spontaneously recovered (SR) group (OR = 1.44 [95% CI 1.11-1.87], P = 0.006,
      P(corr) = 0.02). By Cox relative hazard analysis, both SPP1-ht2 and -1,800G > T
      were associated with age of HCC occurrence among chronic hepatitis patients, e.g.
      ht2/h2- and 1800T/T-bearing patients showed earlier progression to HCC than did
      others (RH = 1.85, P = 0.004, P(corr) = 0.01 and RH = 1.85, P = 0.003, P(corr) =
      0.01, respectively). CONCLUSION: Our findings suggest that SPP1 polymorphisms
      might be among the genetic factors for HBV clearance and/or HCC occurrence.

PMID- 17496056
TI  - Simultaneous development of Fanconi syndrome and acute renal failure associated
      with cidofovir.

PMID- 17496057
TI  - Prolonged survival of an HIV-infected subject with severe lymphoproliferative
      disease and rhinocerebral mucormycosis.

PMID- 17496058
TI  - Community emergence of CTX-M type extended-spectrum beta-lactamases among urinary
      Escherichia coli from women.
AB  - OBJECTIVES: To conduct a territory-wide study of extended-spectrum beta
      lactamases (ESBLs) among community isolates of urinary Escherichia coli from
      women in Hong Kong. METHODS: Up to 50 consecutive single-patient E. coli
      isolates, collected from 13 laboratories in 2004, were studied. The ESBLs were
      characterized by PCR sequencing using specific primers. The epidemiological
      relationship of the isolates was studied by PFGE and phylogenetic group PCRs.
      RESULTS: Forty-two ESBL producers were found among 600 consecutive isolates
      tested. The ESBL prevalence was 7.3% (15/205) for women aged 18-35 years, 5%
      (11/219) for women aged 36-50 years, 6.3% (4/63) for women aged 51-64 years and
      10.6% (12/113) for women aged >or=65 years (P=0.3). The ESBL-producing isolates
      were often multidrug-resistant and CTX-M-14 was found in 37 isolates, CTX-M-15 in
      3 isolates and CTX-M-3 in 2 isolates. PFGE revealed no significant clusters among
      the ESBL producers. Overall, CTX-M-14 producers were significantly more likely to
      belong to group D than non-ESBL producers [18/37 (48.6%) versus 13/57 (22.8%),
      P=0.009]. However, 7 of 13 (53.8%) CTX-M-14 producers from women aged 18-35 years
      represented phylogenetic group B2, compared with 7 of 24 (29.2%) for women of all
      other ages (P=0.1). CONCLUSIONS: The study documented the community emergence of
      CTX-M as the predominant ESBL type among urinary isolates from women. The spread
      of CTX-M enzymes among isolates from young women is concerning and deserves close
      monitoring.

PMID- 17496059
TI  - Nitric oxide attenuates epithelial-mesenchymal transition in alveolar epithelial
      cells.
AB  - Patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis
      (IPF) and bronchopulmonary dysplasia (BPD), suffer from lung fibrosis secondary
      to myofibroblast-mediated excessive ECM deposition and destruction of lung
      architecture. Transforming growth factor (TGF)-beta1 induces epithelial
      mesenchymal transition (EMT) of alveolar epithelial cells (AEC) to myofibroblasts
      both in vitro and in vivo. Inhaled nitric oxide (NO) attenuates ECM accumulation,
      enhances lung growth, and decreases alveolar myofibroblast number in experimental
      models. We therefore hypothesized that NO attenuates TGF-beta1-induced EMT in
      cultured AEC. Studies of the capacity for endogenous NO production in AEC
      revealed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide
      synthase (iNOS) are expressed and active in AEC. Total NOS activity was 1.3 pmol
      x mg protein(-1) x min(-1) with 67% derived from eNOS. TGF-beta1 (50 pM)
      suppressed eNOS expression by more than 60% and activity by 83% but did not
      affect iNOS expression or activity. Inhibition of endogenous NOS with l-NAME led
      to spontaneous EMT, manifested by increased alpha-smooth muscle actin (alpha-SMA)
      expression and a fibroblast-like morphology. Provision of exogenous NO to TGF
      beta1-treated AEC decreased stress fiber-associated alpha-SMA expression and
      decreased collagen I expression by 80%. NO-treated AEC also retained an
      epithelial morphology and expressed increased lamellar protein, E-cadherin, and
      pro-surfactant protein B compared with those treated with TGF-beta alone. These
      findings indicate that NO serves a critical role in preserving an epithelial
      phenotype and in attenuating EMT in AEC. NO-mediated regulation of AEC fate may
      have important implications in the pathophysiology and treatment of diseases such
      as IPF and BPD.

PMID- 17496060
TI  - Identification of multiple MAPK-mediated transcription factors regulated by
      tobacco smoke in airway epithelial cells.
AB  - Activation and regulation of transcription factors (TFs) are the major mechanisms
      regulating changes in gene expression upon environmental exposure. Tobacco smoke
      (TS) is a complex mixture of chemicals, each of which could act through different
      signal cascades, leading to the regulation of distinct TFs and alterations in
      subsequent gene expression. We proposed that TS exposure affects inflammatory
      gene expression at the transcriptional level by modulating the DNA binding
      activities of TFs. To investigate transcriptional regulation upon TS exposure, a
      protein/DNA array was applied to screen TFs that are affected by TS exposure.
      This array-based screening allowed us to simultaneously detect 244 different TFs.
      Our results indicated that multiple TFs were rapidly activated upon TS exposure.
      DNA-binding activity of differentially expressed TFs was confirmed by EMSA. Our
      results showed that at least 20 TFs displayed more than twofold expressional
      changes after smoke treatment. Ten smoke-induced TFs, including NF-kappaB, VDR,
      ISRE, and RSRFC4, were involved in MAPK signaling pathways. The NF-kappaB family,
      which is involved in inflammation-induced gene activation, was selected for
      further study to characterize TS exposure-induced transcriptional activation.
      Western blot analysis and immunofluorescence microscopy indicated that TS
      exposure induced phosphorylation of IkappaB and translocation of NF-kappaB
      p65/p50 heterodimers into the nucleus. This activity was abrogated by the MAPK
      inhibitors PD98059 and U0126. Our results confirmed that activation of MAPK
      signaling pathways by TS exposure increased transcriptional activity of NF
      kappaB. These data provide a potential mechanism for TS-induced inflammatory gene
      expression.

PMID- 17496061
TI  - Regulation of surfactant secretion in alveolar type II cells.
AB  - Molecular mechanisms of surfactant delivery to the air/liquid interface in the
      lung, which is crucial to lower the surface tension, have been studied for more
      than two decades. Lung surfactant is synthesized in the alveolar type II cells.
      Its delivery to the cell surface is preceded by surfactant component synthesis,
      packaging into specialized organelles termed lamellar bodies, delivery to the
      apical plasma membrane and fusion. Secreted surfactant undergoes reuptake,
      intracellular processing, and finally resecretion of recycled material. This
      review focuses on the mechanisms of delivery of surfactant components to and
      their secretion from lamellar bodies. Lamellar bodies-independent secretion is
      also considered. Signal transduction pathways involved in regulation of these
      processes are discussed as well as disorders associated with their malfunction.

PMID- 17496062
TI  - Lipid A fraction of LPS induces a discrete MAPK activation in acute lung injury.
AB  - Lipopolysaccharide (LPS) induces acute lung injury (ALI) via Toll-like receptor 4
      (TLR4)-mediated MAPK activation. The lipid A fraction of LPS is considered to be
      the active moiety, but whether the lipid A-TLR4 interaction accounts completely
      for ALI-associated MAPK activation in vivo has not been determined. The lipid A
      fraction of LPS induces a discrete MAPK activation pattern in murine ALI. Mice
      (C57BL/6J, C3H/HeJ) were treated with intratracheal instillations of purified
      lipid A or LPS (10, 30, and 100 microg per mouse) or vehicle. ALI was assessed by
      histology. Chromogenic myeloperoxidase (MPO) activity was measured in lung
      homogenates. MAPK expression was quantified by immunoblotting. In vitro ERK
      inhibitor studies using thioglycollate-elicited macrophages were also performed.
      MPO increased in a dose- and time-responsive fashion. Notably, MPO was 2.4-fold
      greater after lipid A compared with LPS and vehicle at 6 h after instillation
      (lipid A, 0.88 +/- 0.25 vs. LPS, 0.37 +/- 0.21 optical density units.min(-1).mg(
      1); P < 0.05). However, ALI scores were comparable at 6 and 24 h between LPS and
      lipid A. MPO was also comparable in vehicle-treated or C3H/HeJ mice treated with
      LPS or lipid A at 6 and 24 h. Phospho-ERK activation was pronounced at 6 and 24 h
      after lipid A but not LPS treatment. In vitro studies confirmed the relationship
      between phospho-ERK activation and cytokine expression in macrophage stimulated
      with either LPS or lipid A. Compared with whole LPS, the lipid A fraction is
      associated with amplified whole lung MPO and ERK activation 6 h after
      intratracheal instillation in mice.

PMID- 17496063
TI  - The role of DNA and actin polymers on the polymer structure and rheology of
      cystic fibrosis sputum and depolymerization by gelsolin or thymosin beta 4.
AB  - Mucus clearance is the first line of pulmonary defense against inhaled irritants,
      microorganisms, and allergens. In health, the gel-forming mucins are the
      principal polymeric components of airway mucus but in cystic fibrosis (CF), the
      necrotic death of inflammatory and epithelial cells releases a network of
      copolymerized extracellular DNA and filamentous (F-) actin-producing secretions
      that are similar to pus and difficult to clear by cilia or airflow. The large
      amounts of F-actin in CF sputum suggested that thymosin beta4 (Tbeta4) or
      gelsolin could depolymerize the secondary polymer network of CF sputum. Dose
      dependent CF sputum rheology and polymer structure were measured before and after
      the addition of excipient, dornase alfa, Tbeta4, gelsolin, and Tbeta4 or gelsolin
      with dornase for 30 min. Sputum was also incubated with Tbeta4 30 microg/mL,
      gelsolin 10 microg/mL or excipient for 0, 5, 10, 15, 20, or 60 min. There was a
      dose-dependent decrease in cohesivity with Tbeta4 and a time-dependent decrease
      in cohesivity at 30 microg/mL. With the combination of dornase alfa and Tbeta4 at
      1.5 microg/mL, there was a 65% decrease in elasticity (P = 0.013). There was a
      time-dependent decrease in cohesivity (P = 0.0004) and elasticity (P = 0.047)
      with gelsolin and a dose-dependent fall in cohesivity (P = 0.0008). An apparent
      synergy of Tbeta4 or gelsolin on actin and dornase on DNA may be explained by the
      combined effect of actin depolymerization and DNA filament severing or by virtue
      of actin depolymerization increasing the effectiveness of dornase alfa.

PMID- 17496064
TI  - Saccadometry: the possible application of latency distribution measurement for
      monitoring concussion.
AB  - Premature return to play after concussion may have debilitating or even fatal
      consequences. Computerised neuropsychological test batteries are widely used to
      monitor recovery, but none meet all specified criteria. One possible alternative
      is to measure saccadic reaction time or latency. Latency reflects the operation
      of cerebral decision mechanisms, and is strongly influenced by many agents that
      impair cortical function. A portable, micro-miniature device (saccadometer) was
      used to record the eye movements of amateur boxers before and after competitive
      bouts. Individual latency distributions were significantly affected after blows
      to the head, though the effects seemed to be reversible, with recovery over a few
      days. This quantitative, objective and easy to use technique should perhaps be
      deployed more widely to evaluate its potential in monitoring the effects of
      sports-related head injuries.

PMID- 17496065
TI  - Influence of exercise on oxidant stress products in elite Indian cyclists.
AB  - The influence of exercise on free-radical chemistry is not well understood. It is
      yet to be confirmed whether an adequate biochemical defence system exists in the
      human body to provide protection from oxy-centred radicals generated by exercise.
      Fifty trained elite cyclists undertaking exhaustive endurance training were
      compared with a control group of 50 sedentary workers. Serum malondialdehyde
      (MDA), uric acid, superoxide dismutase (SOD), catalase, vitamin E, vitamin C and
      susceptibility to oxidative stress were assessed. Exhaustive exercise resulted in
      significantly (p<0.05) higher concentrations of serum MDA, vitamin E and vitamin
      C, significantly (p<0.001) higher SOD activity, but less significantly (p<0.01)
      higher concentrations of uric acid and significantly (p<0.05) lower catalase
      activity in elite cyclists than in the controls. Alterations in the activities of
      erythrocyte scavenger enzymes (SOD) and higher level of non-enzymatic defences in
      trained subjects may not be sufficient to counteract the increase in reactive
      oxygen species produced by endurance training.

PMID- 17496066
TI  - Sclerosing therapy and eccentric training in flexor carpi radialis tendinopathy
      in a tennis player.
AB  - BACKGROUND: Tendinopathy of the flexor carpi ulnaris tendon is a rare entity.
      Recent research revealed the role of a neurovascular ingrowth at the point of
      pain in various tendinopathic locations, such as at the Achilles and patellar
      tendon, in plantar fasciitis as well as in supraspinatus and tennis elbow
      tendinopathy. However, beyond the elbow no such neovascularisation has been
      reported to date. METHODS: We present a 35-year old tennis player suffering
      tremendous pain (visual analogue scale (VAS) rating of 9/10) at the flexor carpi
      ulnaris tendon with adjacent calcification in close proximity to the pisiform
      bone. The patient was assessed with power Doppler and laser Doppler
      quantification of neovascularisation at the point of pain. RESULTS: Power Doppler
      and laser Doppler quantification of neovascularisation at the point of pain
      identified higher capillary blood flow at three points over the painful vs the
      non-painful tendon (146/240/232rU vs 93/74/70rU at the non-affected side).
      Sclerosing therapy using polidocanol under power and laser Doppler guidance was
      initiated, with immediate decrease of capillary blood flow by 25% with resolution
      of the neovascularisation in power Doppler. Immediately following sclerosing, the
      patient's reported pain level on the VAS was reduced from 9/10 to 4/10. Following
      a short period of rest, eccentric training of the forearm muscle was initiated
      over 12 weeks with functional complete recovery and complete resolution of wrist
      pain. CONCLUSION: Sclerosing therapy using polidocanol under power- and laser
      Doppler guidance can decrease capillary blood flow by 25% with resolution of the
      neovascularisation. Subsequent eccentric training of the forearm muscle over 12
      weeks can result in complete resolution of wrist pain.

PMID- 17496067
TI  - Factors associated with menstrual dysfunction and self-reported bone stress
      injuries in female runners in the ultra- and half-marathons of the Two Oceans.
AB  - OBJECTIVE: To investigate factors associated with menstrual dysfunction, self
      reported bone stress injuries and energy balance in women runners. METHODS: 613
      runners were randomly sampled during the registration period for an endurance
      event. Demographic information, including self-reported height and weight,
      training and injury history and menstrual history, was collected by
      questionnaire. RESULTS: Ultra-marathon (ULTRA) participants (n = 276) were
      significantly older (mean (SD) 39 (8.2) vs 34 (10.5) years; p<0.001), lighter
      (58.2 (6.6) vs 59.6 (8.3) kg; p<0.05) and reported a higher training volume
      (p<0.001) than half-marathon (HALF) participants (n = 337). Significantly more
      ULTRA subjects than HALF subjects reported a previous bone stress injury (21% vs
      14%; p<0.05). There was no difference between the groups for menstrual status,
      but age at menarche was later (p<0.01) in the ULTRA group. Data were combined
      according to the absence (REG; n = 368/602 (61%)) or presence (IRREG; n = 234/602
      (39%)) of a history of menstrual irregularity. Subject morphology was similar
      between groups, but the IRREG group had a higher self-reported measure on the
      self-loathing subscale (SLSS; p<0.01). The whole group was then classified
      according to current menstrual status, with 165 women being classified as
      currently irregular. (OLIGO/AMEN; 11.6%) and 445 women as currently regular
      (EUMEN; 88.4%). There were no morphological differences between the groups,
      however the OLIGO/AMEN group had a later age of menarche (p<0.01) than the EUMEN
      group. Further, women who reported a previous bone stress injury had higher SLSS
      scores than those who did not (2.91 (0.98) vs 2.68 (0.84); p<0.05). CONCLUSIONS:
      There may be two independent mechanisms associated with energy balance, which are
      related to bone stress injuries, but may not necessarily be related to menstrual
      dysfunction.

PMID- 17496068
TI  - No neurochemical evidence for brain injury caused by heading in soccer.
AB  - BACKGROUND: The possible injurious effect to the brain of heading in soccer is a
      matter of discussion. OBJECTIVE: To determine whether standardised headings in
      soccer are associated with increased levels of biochemical markers for neuronal
      injury in cerebrospinal fluid (CSF) and serum. METHODS: 23 male amateur soccer
      players took part in a heading training session involving heading a ball kicked
      from a distance of 30 m at least 10 m forward. Ten players performed 10 and 13
      players performed 20 approved headings. The players underwent lumbar puncture and
      serum sampling 7-10 days after the headings. The study also included 10 healthy
      male non-athletic control subjects. CSF was analysed for neurofilament light
      protein, total tau, glial fibrillary acidic protein, S-100B and albumin
      concentrations. Serum was analysed for S-100B and albumin. RESULTS: None of the
      biomarker levels were abnormal and there were no significant differences between
      any of the three groups, except for a slightly increased CSF S-100B concentration
      in controls compared with headers. Biomarker levels did not correlate with the
      number of headings performed. CONCLUSION: Repeated low-severity head impacts due
      to heading in soccer are not associated with any neurochemical signs of injury to
      the brain.

PMID- 17496069
TI  - Head injuries in the female football player: incidence, mechanisms, risk factors
      and management.
AB  - Although all injuries in sports are a concern for participants, head injuries are
      particularly troublesome because of the potential for long-term cognitive
      deficits. To prevent any specific injury, it is important to understand the basic
      frequency and incidence of injury and then the mechanism of injury. Once these
      are established, prevention programmes can be tested to see if the rate of injury
      changes. A primary problem with head injuries is recognising that the injury has
      occurred. Many athletes are not aware of the seriousness of concussive injury,
      thus this type of injury is probably under-reported. Once the diagnosis of a
      concussion is made, the next difficult decision is when to return a player to the
      game. These two management issues dominate the continuing development of
      understanding of concussive head injury. This paper explores the known gender
      differences between head injuries and highlights the areas that need to be
      considered in future research.

PMID- 17496070
TI  - Strategies to prevent injury in adolescent sport: a systematic review.
AB  - This systematic review set out to identify randomised controlled trials and
      controlled intervention studies that evaluated the effectiveness of preventive
      strategies in adolescent sport and to draw conclusions on the strength of the
      evidence. A literature search in seven databases (Medline, SportDiscus, EMBASE,
      CINAHL, PEDro, Cochrane Review and DARE) was carried out using four keywords:
      adolescent, sport, injury and prevention (expanded to capture any relevant
      literature). Assessment of 154 papers found 12 studies eligible for inclusion. It
      can be concluded that injury prevention strategies that focus on preseason
      conditioning, functional training, education, balance and sport-specific skills,
      which should be continued throughout the sporting season, are effective. The
      evidence for the effectiveness of protective equipment in injury prevention is
      inconclusive and requires further assessment.

PMID- 17496071
TI  - Rectus sheath haematoma: a rare presentation of non-contact strenuous exercises.
AB  - Rectus sheath haematoma (RSH) is a well-documented but uncommon clinical
      condition. It is usually a self-limiting condition but can present as a life
      threatening emergency. RSH after non-contact vigorous exercise is unknown. Two
      such cases secondary to yoga and laughter therapy sessions, respectively, are
      reported. One of them required surgical intervention, whereas the other was
      successfully treated conservatively.

PMID- 17496073
TI  - Effects of experience in a dynamic environment on postural control.
AB  - BACKGROUND: Surfing is a balance-reliant, open skill performed in a dynamic
      environment rich in visual, somatosensory and vestibular information. OBJECTIVE:
      To evaluate adaptations to the postural control system by surfing experience.
      METHODS: Postural control was assessed in an upright bipedal stance in 60 male
      volunteers (21 elite surfers, 20 intermediate level surfers, and 19 controls)
      using various closed-stance positions. Six tasks were performed with two trials
      including a cognitive task, in the following order: eyes open, head in a neutral
      position (EO1); eyes closed, head in a neutral position (EC); eyes closed, head
      back (ECHB); eyes open, head in a neutral position, cognitive task 1 (EOC1); eyes
      open head in a neutral position, cognitive task 2 (EOC2); eyes open head in a
      neutral position (EO2). Dependent variables were area of 95th centile ellipse
      (AoE) and sway path length (SPL). RESULTS: All participants showed systematic
      increases in SPL and AoE in EC and ECHB trials. Expert surfers displayed
      significantly (p<0.05) increased SPL but not AoE when sharing attention with both
      concurrent mental tasks compared with controls. Controls showed a slight, non
      significant change in postural control (reduced SPL and AoE) when attending to
      concurrent mental tasks. CONCLUSIONS: The findings indicate that standard
      postural sway indices are not able to elucidate whether expertise in surfing
      facilitates adaptations to the postural control system. However, concurrent
      mental task findings illustrate that systematic differences in balance abilities
      between expert surfers and controls may exist.

PMID- 17496072
TI  - Nitric oxide synthase-derived plasma nitrite predicts exercise capacity.
AB  - BACKGROUND: Nitrite is the main oxidation product of nitric oxide (NO) in plasma.
      It sensitively reflects changes in endothelial NO synthase (eNOS) activity under
      fasting conditions and serves as an endocrine NO donor, contributing to the
      regulation of blood flow through reaction with haemoglobin. As NO is necessary to
      maintain an adequate vascular response to the increased demands of blood flow, it
      is believed to be important for vasodilation induced by exercise. OBJECTIVE: To
      investigate whether the capacity of the vasculature to produce nitrite is
      associated with exercise performance. DESIGN: With the use of chemiluminescence
      detection, nitrite concentrations in 55 healthy subjects (mean (SEM) age 40 (2)
      years; 22 men) were studied before and after an exercise test, and endothelial
      function was determined by measuring flow-mediated dilation of the brachial
      artery using high-resolution ultrasound. In a subset of subjects, the NOS
      inhibitor, N(G)-monomethyl-L-arginine, was applied to elucidate the effect of
      eNOS on changes in nitrite. RESULTS: Exercise significantly (p<0.001) increased
      plasma nitrite from 97 (6) to 125 (8) nM. The relative increase in plasma nitrite
      was related to flow-mediated dilation (6.1 (0.3)%; r = 0.36; p = 0.01). N(G)
      Monomethyl-L-arginine blocked increases in nitrite. Post-exercise nitrite
      concentration correlated with exercise performance, as determined by maximally
      reached stress power (r = 0.37; p<0.007), and inversely with age. Multivariate
      analysis showed that both age and post-exercise nitrite concentration were
      independent predictors of stress endurance and power. CONCLUSION: The results
      suggest a role for plasma nitrite in the adaptation of haemodynamics during
      exercise. An impaired increase in plasma nitrite may limit exercise capacity.

PMID- 17496074
TI  - Exercise pretraining protects against cerebral ischaemia induced by heat stroke
      in rats.
AB  - BACKGROUND: In the rat brain, heat-stroke-induced damage to cerebral neurons is
      attenuated through heat-shock-induced overexpression of heat-shock protein 72
      (HSP72). OBJECTIVE: To ascertain whether progressive exercise preconditioning
      induces HSP72 expression in the rat brain and prevents heat-stroke-induced
      cerebral ischaemia and injury. METHODS: Male Wistar rats were randomly assigned
      to either a sedentary group or an exercise group. Those in the exercise group
      progressively ran on a treadmill 5 days/week, for 30-60 min/day at an intensity
      of 20-30 m/min for 3 weeks. The effects of heat stroke on mean arterial pressure,
      cerebral blood flow, brain ischaemia markers (glutamate, lactate/pyruvate ratio
      and nitric oxide), a cerebral injury marker (glycerol) and brain neuronal damage
      score in the preconditioned animals were compared with effects in unexercised
      controls. Heat stroke was induced by exposing urethane-anaesthetised animals to a
      temperature of 43 degrees C for 55 min, which caused the body temperature to
      reach 42 degrees C. RESULTS: Three weeks of progressive exercise pretreatment
      induced HSP72 preconditioning in the brain and conferred significant protection
      against heat-stroke-induced hyperthermia, arterial hypotension, cerebral
      ischaemia and neuronal damage; it also prolonged survival. CONCLUSIONS: Exercise
      for 3 weeks can improve heat tolerance as well as attenuate heat-stroke-induced
      cerebral ischaemia in rats. The maintenance of mean arterial pressure and
      cerebral blood flow at appropriate levels in the rat brain may be related to
      overexpression of HSP72.

PMID- 17496075
TI  - VapC-1 of nontypeable Haemophilus influenzae is a ribonuclease.
AB  - Nontypeable Haemophilus influenzae (NTHi) organisms are obligate parasites of the
      human upper respiratory tract that can exist as commensals or pathogens. Toxin
      antitoxin (TA) loci are highly conserved gene pairs that encode both a toxin and
      antitoxin moiety. Seven TA gene families have been identified to date, and NTHi
      carries two alleles of the vapBC family. Here, we have characterized the function
      of one of the NTHi alleles, vapBC-1. The gene pair is transcribed as an operon in
      two NTHi clinical isolates, and promoter fusions display an inverse relationship
      to culture density. The antitoxin VapB-1 forms homomultimers both in vitro and in
      vivo. The expression of the toxin VapC-1 conferred growth inhibition to an
      Escherichia coli expression strain and was successfully purified only when cloned
      in tandem with its cognate antitoxin. Using total RNA isolated from both E. coli
      and NTHi, we show for the first time that VapC-1 is an RNase that is active on
      free RNA but does not degrade DNA in vitro. Preincubation of the purified toxin
      and antitoxin together results in the formation of a protein complex that
      abrogates the activity of the toxin. We conclude that the NTHi vapBC-1 gene pair
      functions as a classical TA locus and that the induction of VapC-1 RNase activity
      leads to growth inhibition via the mechanism of mRNA cleavage.

PMID- 17496076
TI  - Histidine auxotrophy in commensal and disease-causing nontypeable Haemophilus
      influenzae.
AB  - Histidine biosynthesis is one of the best studied metabolic pathways in bacteria.
      Although this pathway is thought to be highly conserved within and between
      bacterial species, a previous study identified a genetic region within the
      histidine operon (his) of nontypeable strains of Haemophilus influenzae (NTHI)
      that was more prevalent among otitis media strains than among throat commensal
      NTHI strains. In the present study, we further characterized this region and
      showed that genes in the complete his operon (hisG, -D, -C, -NB, -H, -A, -F, and 
      IE) are >99% conserved among four fully sequenced NTHI strains, are present in
      the same location in these four genomes, and are situated in the same gene order.
      Using PCR and dot blot hybridization, we determined that the his operon was
      significantly more prevalent in otitis media NTHI strains (106/121; 87.7%) than
      in throat strains (74/137; 54%) (prevalence ratio, 1.62; P<0.0001), suggesting a
      possible role in middle ear survival and/or acute otitis media. NTHI strains
      lacking the his operon showed attenuated growth in histidine-restricted media,
      confirming them as his-negative auxotrophs. Our results suggest that the ability
      to make histidine is an important factor in bacterial growth and survival in the
      middle ear, where nutrients such as histidine may be found in limited amounts.
      Those isolates lacking the histidine pathway were still able to survive well in
      the throat, which suggests that histidine is readily available in the throat
      environment.

PMID- 17496077
TI  - Two ABC transporter operons and the antimicrobial resistance gene mtrF are pilT
      responsive in Neisseria gonorrhoeae.
AB  - Retraction of type IV pili is mediated by PilT. We show that loss of pilT
      function leads to upregulation of mtrF (multiple transferable resistance) and two
      operons encoding putative ABC transporters in Neisseria gonorrhoeae MS11. This
      effect occurs indirectly through the transcriptional regulator FarR, which until
      now has been shown to regulate only farAB. L-Glutamine can reverse pilT
      downregulation of the ABC transporter operons and mtrF.

PMID- 17496078
TI  - Transcriptional regulation of the virR operon of the intracellular pathogen
      Rhodococcus equi.
AB  - The virR operon, located on the virulence plasmid of the intracellular pathogen
      Rhodococcus equi, contains five genes, two of which (virR and orf8) encode
      transcriptional regulators. The first gene of the operon (virR), encoding a LysR
      type transcriptional regulator, is transcribed at a constitutive low level,
      whereas the four downstream genes are induced by low pH and high growth
      temperature. Differential regulation of the virR operon genes could not be
      explained by differential mRNA stability, as there were no major differences in
      mRNA half-lives of the transcripts representing each of the five genes within the
      virR operon. Transcription of virR is driven by the P(virR) promoter, with a
      transcription start site 53 bp upstream of the virR initiation codon. The four
      genes downstream of virR are transcribed from P(virR) and from a second promoter,
      P(orf5), located 585 bp downstream of the virR initiation codon. VirR binds to a
      site overlapping the initiation codon of virR, resulting in negative
      autoregulation of the virR gene, explaining its low constitutive transcription
      level. The P(orf5) promoter is induced by high temperature and low pH, thus
      explaining the observed differential gene expression of the virR operon. VirR has
      a positive effect on P(orf5) activity, whereas the response regulator encoded by
      orf8 is not involved in regulating transcription of the virR operon. The P(virR)
      promoter is strikingly similar to those recognized by the principal sigma factors
      of Streptomyces and Mycobacterium, whereas the P(orf5) promoter does not share
      sequence similarity with P(virR). This suggests that P(orf5) is recognized by an
      alternative sigma factor.

PMID- 17496079
TI  - Global transcriptional analysis of Streptococcus mutans sugar transporters using
      microarrays.
AB  - The transport of carbohydrates by Streptococcus mutans is accomplished by the
      phosphoenolpyruvate-phosphotransferase system (PTS) and ATP-binding cassette
      (ABC) transporters. To undertake a global transcriptional analysis of all S.
      mutans sugar transporters simultaneously, we used a whole-genome expression
      microarray. Global transcription profiles of S. mutans UA159 were determined for
      several monosaccharides (glucose, fructose, galactose, and mannose),
      disaccharides (sucrose, lactose, maltose, and trehalose), a beta-glucoside
      (cellobiose), oligosaccharides (raffinose, stachyose, and maltotriose), and a
      sugar alcohol (mannitol). The results revealed that PTSs were responsible for
      transport of monosaccharides, disaccharides, beta-glucosides, and sugar alcohol.
      Six PTSs were transcribed only if a specific sugar was present in the growth
      medium; thus, they were regulated at the transcriptional level. These included
      transporters for fructose, lactose, cellobiose, and trehalose and two
      transporters for mannitol. Three PTSs were repressed under all conditions tested.
      Interestingly, five PTSs were always highly expressed regardless of the sugar
      source used, presumably suggesting their availability for immediate uptake of
      most common dietary sugars (glucose, fructose, maltose, and sucrose). The ABC
      transporters were found to be specific for oligosaccharides, raffinose,
      stachyose, and isomaltosaccharides. Compared to the PTSs, the ABC transporters
      showed higher transcription under several tested conditions, suggesting that they
      might be transporting multiple substrates.

PMID- 17496080
TI  - Identical, independent, and opposing roles of ppGpp and DksA in Escherichia coli.
AB  - The recent discovery that the protein DksA acts as a coregulator of genes
      controlled by ppGpp led us to investigate the similarities and differences
      between the relaxed phenotype of a ppGpp-deficient mutant and the phenotype of a
      strain lacking DksA. We demonstrate that the absence of DksA and ppGpp has
      similar effects on many of the observed phenotypes but that DksA and ppGpp also
      have independent and sometimes opposing roles in the cell. Specifically, we show
      that overexpression of DksA can compensate for the loss of ppGpp with respect to
      transcription of the promoters P(uspA), P(livJ), and P(rrnBP1) as well as amino
      acid auxotrophy, cell-cell aggregation, motility, filamentation, and stationary
      phase morphology, suggesting that DksA can function without ppGpp in regulating
      gene expression. In addition, ppGpp and DksA have opposing effects on adhesion.
      In the course of our analysis, we also discovered new features of the relaxed
      mutant, namely, defects in cell-cell aggregation and motility.

PMID- 17496081
TI  - Quorum-sensing regulation of the biofilm matrix genes (pel) of Pseudomonas
      aeruginosa.
AB  - Quorum sensing (QS) has been previously shown to play an important role in the
      development of Pseudomonas aeruginosa biofilms (D. G. Davies et al., Science
      280:295-298, 1998). Although QS regulation of swarming and DNA release has been
      shown to play important roles in biofilm development, regulation of genes
      directly involved in biosynthesis of biofilm matrix has not been described. Here,
      transcription of the pel operon, essential for the production of a glucose-rich
      matrix exopolysaccharide, is shown to be greatly reduced in lasI and rhlI
      mutants. Chemical complementation of the lasI mutant with 3-oxo-dodecanoyl
      homoserine lactone restores pel transcription to the wild-type level and biofilm
      formation ability. These findings thus connect QS signaling and transcription of
      genes responsible for biofilm matrix biosynthesis.

PMID- 17496082
TI  - Vibrio cholerae strains possess multiple strategies for abiotic and biotic
      surface colonization.
AB  - Despite its notoriety as a human pathogen, Vibrio cholerae is an aquatic microbe
      suited to live in freshwater, estuarine, and marine environments where biofilm
      formation may provide a selective advantage. Here we report characterization of
      biofilms formed on abiotic and biotic surfaces by two non-O1/O139 V. cholerae
      strains, TP and SIO, and by the O1 V. cholerae strain N16961 in addition to the
      isolation of 44 transposon mutants of SIO and TP impaired in biofilm formation.
      During the course of characterizing the mutants, 30 loci which have not
      previously been associated with V. cholerae biofilms were identified. These loci
      code for proteins which perform a wide variety of functions, including amino acid
      metabolism, ion transport, and gene regulation. Also, when the plankton
      colonization abilities of strains N16961, SIO, and TP were examined, each strain
      showed increased colonization of dead plankton compared with colonization of live
      plankton (the dinoflagellate Lingulodinium polyedrum and the copepod Tigriopus
      californicus). Surprisingly, most of the biofilm mutants were not impaired in
      plankton colonization. Only mutants impaired in motility or chemotaxis showed
      reduced colonization. These results indicate the presence of both conserved and
      variable genes which influence the surface colonization properties of different
      V. cholerae subspecies.

PMID- 17496083
TI  - Temperature-hypersensitive sites of the flagellar switch component FliG in
      Salmonella enterica serovar typhimurium.
AB  - Three flagellar proteins, FliG, FliM, and FliN (FliGMN), are the components of
      the C ring of the flagellar motor. The genes encoding these proteins are
      multifunctional; they show three different phenotypes (Fla(-), Mot(-), and Che(
      )), depending on the sites and types of mutations. Some of the Mot(-) mutants
      previously characterized are found to be motile. Reexamination of all Mot(-)
      mutants in fliGMN genes so far studied revealed that many of them are actually
      temperature sensitive (TS); that is, they are motile at 20 degrees C but
      nonmotile at 37 degrees C. There were two types of TS mutants: one caused a loss
      of function that was not reversed by a return to the permissive temperature
      (rigid TS), and the other caused a loss that was reversed (hyper-TS). The rigid
      TS mutants showed an all-or-none phenotype; that is, once a structure was formed,
      the structure and function were stable against temperature shifts. All of fliM
      and fliN and most of the fliG TS mutants belong to this group. On the other hand,
      the hyper-TS mutants (three of the fliG mutants) showed a temporal swimming/stop
      phenotype, responding to temporal temperature shifts when the structure was
      formed at a permissive temperature. Those hyper-TS mutation sites are localized
      in the C-terminal domain of the FliG molecules at sites that are different from
      the previously proposed functional sites. We discuss a role for this new region
      of FliG in the torque generation of the flagellar motor.

PMID- 17496084
TI  - Adaptor function of PapF depends on donor strand exchange in P-pilus biogenesis
      of Escherichia coli.
AB  - P-pilus biogenesis occurs via the highly conserved chaperone-usher pathway and
      involves the strict coordination of multiple subunit proteins. All nonadhesin
      structural P-pilus subunits possess the same topology, consisting of two domains:
      an incomplete immunoglobulin-like fold (pilin body) and an N-terminal extension.
      Pilus subunits form interactions with one another through donor strand exchange,
      occurring at the usher, in which the N-terminal extension of an incoming subunit
      completes the pilin body of the preceding subunit, allowing the incorporation of
      the subunit into the pilus fiber. In this study, pilus subunits in which the N
      terminal extension was either deleted or swapped with that of another subunit
      were used to examine the role of each domain of PapF in functions involving donor
      strand exchange and hierarchical assembly. We found that the N-terminal extension
      of PapF is required to adapt the PapG adhesin to the tip of the fiber. The pilin
      body of PapF is required to efficiently initiate assembly of the remainder of the
      pilus, with the assistance of the N-terminal extension. Thus, distinct functions
      were assigned to each region of the PapF subunit. In conclusion, all pilin
      subunits possess the same overall architectural topology; however, each N
      terminal extension and pilin body has specific functions in pilus biogenesis.

PMID- 17496085
TI  - Octanoyl-homoserine lactone is the cognate signal for Burkholderia mallei BmaR1
      BmaI1 quorum sensing.
AB  - Acyl-homoserine lactones (HSLs) serve as quorum-sensing signals for many
      Proteobacteria. Members of the LuxI family of signal generators catalyze the
      production of acyl-HSLs, which bind to a cognate receptor in the LuxR family of
      transcription factors. The obligate animal pathogen Burkholderia mallei produces
      several acyl-HSLs, and the B. mallei genome has four luxR and two luxI homologs,
      each of which has been established as a virulence factor. To begin to delineate
      the relevant acyl-HSL signals for B. mallei LuxR homologs, we analyzed the BmaR1
      BmaI1 system. A comparison of acyl-HSL profiles from B. mallei ATCC 23344 and a
      B. mallei bmaI1 mutant indicates that octanoyl-HSL synthesis is BmaI1 dependent.
      Furthermore, octanoyl-HSL is the predominant acyl-HSL produced by BmaI1 in
      recombinant Escherichia coli. The synthesis of soluble BmaR1 in recombinant E.
      coli requires octanoyl-HSL or decanoyl-HSL. Insoluble aggregates of BmaR1 are
      produced in the presence of other acyl-HSLs and in the absence of acyl-HSLs. The
      bmaI1 promoter is activated by BmaR1 and octanoyl-HSL, and a 20-bp inverted
      repeat in the bmaI1 promoter is required for bmaI1 activation. Purified BmaR1
      binds to this promoter region. These findings implicate octanoyl-HSL as the
      signal for BmaR1-BmaI1 quorum sensing and show that octanoyl-HSL and BmaR1
      activate bmaI1 transcription.

PMID- 17496086
TI  - Functional comparison of the two Bacillus anthracis glutamate racemases.
AB  - Glutamate racemase activity in Bacillus anthracis is of significant interest with
      respect to chemotherapeutic drug design, because L-glutamate stereoisomerization
      to D-glutamate is predicted to be closely associated with peptidoglycan and
      capsule biosynthesis, which are important for growth and virulence, respectively.
      In contrast to most bacteria, which harbor a single glutamate racemase gene, the
      genomic sequence of B. anthracis predicts two genes encoding glutamate racemases,
      racE1 and racE2. To evaluate whether racE1 and racE2 encode functional glutamate
      racemases, we cloned and expressed racE1 and racE2 in Escherichia coli. Size
      exclusion chromatography of the two purified recombinant proteins suggested
      differences in their quaternary structures, as RacE1 eluted primarily as a
      monomer, while RacE2 demonstrated characteristics of a higher-order species.
      Analysis of purified recombinant RacE1 and RacE2 revealed that the two proteins
      catalyze the reversible stereoisomerization of L-glutamate and D-glutamate with
      similar, but not identical, steady-state kinetic properties. Analysis of the pH
      dependence of L-glutamate stereoisomerization suggested that RacE1 and RacE2 both
      possess two titratable active site residues important for catalysis. Moreover,
      directed mutagenesis of predicted active site residues resulted in complete
      attenuation of the enzymatic activities of both RacE1 and RacE2. Homology
      modeling of RacE1 and RacE2 revealed potential differences within the active site
      pocket that might affect the design of inhibitory pharmacophores. These results
      suggest that racE1 and racE2 encode functional glutamate racemases with similar,
      but not identical, active site features.

PMID- 17496087
TI  - Effect of a recD mutation on DNA damage resistance and transformation in
      Deinococcus radiodurans.
AB  - The bacterium Deinococcus radiodurans is resistant to extremely high levels of
      DNA-damaging agents such as UV light, ionizing radiation, and chemicals such as
      hydrogen peroxide and mitomycin C. The organism is able to repair large numbers
      of double-strand breaks caused by ionizing radiation, in spite of the lack of the
      RecBCD enzyme, which is essential for double-strand DNA break repair in
      Escherichia coli and many other bacteria. The D. radiodurans genome sequence
      indicates that the organism lacks recB and recC genes, but there is a gene
      encoding a protein with significant similarity to the RecD protein of E. coli and
      other bacteria. We have generated D. radiodurans strains with a disruption or
      deletion of the recD gene. The recD mutants are more sensitive than wild-type
      cells to irradiation with gamma rays and UV light and to treatment with hydrogen
      peroxide, but they are not sensitive to treatment with mitomycin C and methyl
      methanesulfonate. The recD mutants also show greater efficiency of transformation
      by exogenous homologous DNA. These results are the first indication that the D.
      radiodurans RecD protein has a role in DNA damage repair and/or homologous
      recombination in the organism.

PMID- 17496088
TI  - Identification of two Mycobacterium smegmatis lipoproteins exported by a SecA2
      dependent pathway.
AB  - The SecA2 protein is part of a specialized protein export system of mycobacteria.
      We set out to identify proteins exported to the bacterial cell envelope by the
      mycobacterial SecA2 system. By comparing the protein profiles of cell wall and
      membrane fractions from wild-type and DeltasecA2 mutant Mycobacterium smegmatis,
      we identified the Msmeg1712 and Msmeg1704 proteins as SecA2-dependent cell
      envelope proteins. These are the first endogenous M. smegmatis proteins
      identified as dependent on SecA2 for export. Both proteins are homologous to
      periplasmic sugar-binding proteins of other bacteria, and both contain functional
      amino-terminal signal sequences with lipobox motifs. These two proteins appeared
      to be genuine lipoproteins as shown by Triton X-114 fractionation and sensitivity
      to globomycin, an inhibitor of lipoprotein signal peptidase. The role of SecA2 in
      the export of these proteins was specific; not all mycobacterial lipoproteins
      required SecA2 for efficient localization or processing. Finally, Msmeg1704 was
      recognized by the SecA2 pathway of Mycobacterium tuberculosis, as indicated by
      the appearance of an export intermediate when the protein was expressed in a
      DeltasecA2 mutant of M. tuberculosis. Taken together, these results indicate that
      a select subset of envelope proteins containing amino-terminal signal sequences
      can be substrates of the mycobacterial SecA2 pathway and that some determinants
      for SecA2-dependent export are conserved between M. smegmatis and M.
      tuberculosis.

PMID- 17496089
TI  - Distinct centromere-like parS sites on the two chromosomes of Vibrio spp.
AB  - Vibrio cholerae, the cause of cholera, has two circular chromosomes. The parAB
      genes on each V. cholerae chromosome act to control chromosome segregation in a
      replicon-specific fashion. The chromosome I (ChrI) parAB genes (parAB1) govern
      the localization of the origin region of ChrI, while the chromosome II (ChrII)
      parAB genes (parAB2) control the segregation of ChrII. In addition to ParA and
      ParB proteins, Par systems require ParB binding sites (parS). Here we identified
      the parS sites on both V. cholerae chromosomes. We found three clustered origin
      proximal ParB1 binding parS1 sites on ChrI. Deletion of these three parS1 sites
      abrogated yellow fluorescent protein (YFP)-ParB1 focus formation in vivo and
      resulted in mislocalization of the ChrI origin region. However, as observed in a
      parA1 mutant, mislocalization of the ChrI origin region in the parS1 mutant did
      not compromise V. cholerae growth, suggesting that additional (non-Par-related)
      mechanisms may mediate the partitioning of ChrI. We also identified 10 ParB2
      binding parS2 sites, which differed in sequence from parS1. Fluorescent
      derivatives of ParB1 and ParB2 formed foci only with the cognate parS sequence.
      parABS2 appears to form a functional partitioning system, as we found that
      parABS2 was sufficient to stabilize an ordinarily unstable plasmid in Escherichia
      coli. Most parS2 sites were located within 70 kb of the ChrII origin of
      replication, but one parS2 site was found in the terminus region of ChrI. In
      contrast, in other sequenced vibrio species, the distribution of parS1 and parS2
      sites was entirely chromosome specific.

PMID- 17496090
TI  - CfaD-dependent expression of a novel extracytoplasmic protein from
      enterotoxigenic Escherichia coli.
AB  - H10407 is a strain of enterotoxigenic Escherichia coli (ETEC) that utilizes CFA/I
      pili to adhere to surfaces of the small intestine, where it elaborates toxins
      that cause profuse watery diarrhea in humans. Expression of the CFA/I pilus is
      positively regulated at the level of transcription by CfaD, a member of the
      AraC/XylS family. DNase I footprinting revealed that the activator has two
      binding sites upstream of the pilus promoter cfaAp. One site extends from
      positions -23 to -56, and the other extends from positions -73 to -103 (numbering
      relative to the transcription start site of cfaAp). Additional CfaD binding sites
      were predicted within the genome of H10407 by computational analysis. Two of
      these sites lie upstream of a previously uncharacterized gene, cexE. In vitro
      DNase I footprinting confirmed that both sites are genuine binding sites, and
      cexEp::lacZ reporters demonstrated that CfaD is required for the expression of
      cexE in vivo. The amino terminus of CexE contains a secretory signal peptide that
      is removed during translocation across the cytoplasmic membrane through the
      general secretory pathway. These studies suggest that CexE may be a novel ETEC
      virulence factor because its expression is controlled by the virulence regulator
      CfaD, and its distribution is restricted to ETEC.

PMID- 17496091
TI  - Low concentrations of bile salts induce stress responses and reduce motility in
      Bacillus cereus ATCC 14579 [corrected].
AB  - Tolerance to bile salts was investigated in forty Bacillus cereus strains,
      including 17 environmental isolates, 11 dairy isolates, 3 isolates from food
      poisoning outbreaks, and 9 other clinical isolates. Growth of all strains was
      observed at low bile salt concentrations, but no growth was observed on LB agar
      plates containing more than 0.005% bile salts. Preincubation of the B. cereus
      type strain, ATCC 14579, in low levels of bile salts did not increase tolerance
      levels. B. cereus ATCC 14579 was grown to mid-exponential growth phase and
      shifted to medium containing bile salts (0.005%). Global expression patterns were
      determined by hybridization of total cDNA to a 70-mer oligonucleotide microarray.
      A general stress response and a specific response to bile salts were observed.
      The general response was similar to that observed in cultures grown in the
      absence of bile salts but at a higher (twofold) cell density. Up-regulation of
      several putative multidrug exporters and transcriptional regulators and down
      regulation of most motility genes were observed as part of the specific response.
      Motility experiments in soft agar showed that motility decreased following bile
      salts exposure, in accordance with the transcriptional data. Genes encoding
      putative virulence factors were either unaffected or down-regulated.

PMID- 17496092
TI  - CcpA-dependent and -independent control of beta-galactosidase expression in
      Streptococcus pneumoniae occurs via regulation of an upstream phosphotransferase
      system-encoding operon.
AB  - A spontaneous mutant of Streptococcus pneumoniae strain D39 exhibiting elevated
      beta-galactosidase activity was identified. We determined that the beta
      galactosidase activity was due to BgaA, a surface protein in S. pneumoniae, and
      that the expression of bgaA was regulated. Transcription analyses demonstrated
      expression of bgaA in the constitutive beta-galactosidase (BgaA(C)) mutant, but
      not in the parent. beta-Galactosidase expression was induced in the parent under
      specific growth conditions; however, the levels did not reach those of the
      BgaA(C) mutant. We localized the mutation resulting in the BgaA(C) phenotype to a
      region upstream of bgaA and in the promoter of a phosphoenolpyruvate-dependent
      phosphotransferase system (PTS) operon. The mutation was in a catabolite
      responsive element (cre) and affected the binding of CcpA (catabolite control
      protein A), a key regulator of many carbon metabolism genes. The pts operon and
      bgaA were cotranscribed, and their transcription was regulated by CcpA. Deletion
      of ccpA altered beta-galactosidase activity, leading to a sevenfold increase in
      the parent but a fivefold decrease in the BgaA(C) mutant. The resulting beta
      galactosidase activities were the same in the two strains, suggesting the
      presence of a second repressor. The presence of glucose in the growth medium
      resulted in pts-bgaA repression by both CcpA and the second repressor, with the
      latter being important in responding to the glucose concentration. Expression of
      beta-galactosidase is important for S. pneumoniae adherence during colonization
      of the nasopharynx, a site normally devoid of glucose. CcpA and environmental
      glucose concentrations thus appear to play important roles in the regulation of a
      niche-specific virulence factor.

PMID- 17496093
TI  - Mycobacterial nonhomologous end joining mediates mutagenic repair of chromosomal
      double-strand DNA breaks.
AB  - Bacterial nonhomologous end joining (NHEJ) is a recently described DNA repair
      pathway best characterized in mycobacteria. Bacterial NHEJ proteins LigD and Ku
      have been analyzed biochemically, and their roles in linear plasmid repair in
      vivo have been verified genetically; yet the contributions of NHEJ to repair of
      chromosomal DNA damage are unknown. Here we use an extensive set of NHEJ- and
      homologous recombination (HR)-deficient Mycobacterium smegmatis strains to probe
      the importance of HR and NHEJ in repairing diverse types of chromosomal DNA
      damage. An M. smegmatis Delta recA Delta ku double mutant has no apparent growth
      defect in vitro. Loss of the NHEJ components Ku and LigD had no effect on
      sensitivity to UV radiation, methyl methanesulfonate, or quinolone antibiotics.
      NHEJ deficiency had no effect on sensitivity to ionizing radiation in logarithmic
      or early-stationary-phase cells but was required for ionizing radiation
      resistance in late stationary phase in 7H9 but not LB medium. In addition, NHEJ
      components were required for repair of I-SceI mediated chromosomal double-strand
      breaks (DSBs), and in the absence of HR, the NHEJ pathway rapidly mutates the
      chromosomal break site. The molecular outcomes of NHEJ-mediated chromosomal DSB
      repair involve predominantly single-nucleotide insertions at the break site,
      similar to previous findings using plasmid substrates. These findings demonstrate
      that prokaryotic NHEJ is specifically required for DSB repair in late stationary
      phase and can mediate mutagenic repair of homing endonuclease-generated
      chromosomal DSBs.

PMID- 17496094
TI  - QseA and GrlR/GrlA regulation of the locus of enterocyte effacement genes in
      enterohemorrhagic Escherichia coli.
AB  - Transcription of the locus of enterocyte effacement (LEE) genes in
      enterohemorrhagic Escherichia coli (EHEC) is regulated by the LEE-encoded Ler and
      GrlR/GrlA proteins as well as the non-LEE-encoded regulator QseA. This work
      demonstrates that GrlR/GrlA activate LEE2 transcription in a Ler-independent
      fashion, whereas transcription of grlRA is activated by QseA in both Ler
      dependent and -independent manners.

PMID- 17496095
TI  - DNA polymerases BI and D from the hyperthermophilic archaeon Pyrococcus furiosus
      both bind to proliferating cell nuclear antigen with their C-terminal PIP-box
      motifs.
AB  - Proliferating cell nuclear antigen (PCNA) is the sliding clamp that is essential
      for the high processivity of DNA synthesis during DNA replication. Pyrococcus
      furiosus, a hyperthermophilic archaeon, has at least two DNA polymerases,
      polymerase BI (PolBI) and PolD. Both of the two DNA polymerases interact with the
      archaeal P. furiosus PCNA (PfuPCNA) and perform processive DNA synthesis in
      vitro. This phenomenon, in addition to the fact that both enzymes display 3'-5'
      exonuclease activity, suggests that both DNA polymerases work in replication fork
      progression. We demonstrated here that both PolBI and PolD functionally interact
      with PfuPCNA at their C-terminal PIP boxes. The mutant PolBI and PolD enzymes
      lacking the PIP-box sequence do not respond to the PfuPCNA at all in an in vitro
      primer extension reaction. This is the first experimental evidence that the PIP
      box motif, located at the C termini of the archaeal DNA polymerases, is actually
      critical for PCNA binding to form a processive DNA-synthesizing complex.

PMID- 17496096
TI  - Only one of four oligopeptide transport systems mediates nitrogen nutrition in
      Staphylococcus aureus.
AB  - Oligopeptides internalized by oligopeptide permease (Opp) transporters play key
      roles in bacterial nutrition, signaling, and virulence. To date, two opp operons,
      opp-1 and opp-2, have been identified in Staphylococcus aureus. Systematic in
      silico analysis of 11 different S. aureus genomes revealed the existence of two
      new opp operons, opp-3 and opp-4, plus an opp-5A gene encoding a putative peptide
      binding protein. With the exception of opp-4, the opp operons were present in all
      S. aureus strains. Within a single strain, the different opp operons displayed
      little sequence similarity and distinct genetic organization. Transcriptional
      studies showed that opp-1, opp-2, opp-3, and opp-4 operons were polycistronic and
      that opp-5A is monocistronic. We designed a minimal chemically defined medium for
      S. aureus RN6390 and showed that all opp genes were expressed but at different
      levels. Where tested, OppA protein production paralleled transcriptional
      profiles. opp-3, which encodes proteins most similar to known peptide transport
      proteins, displayed the highest expression level and was the only transporter to
      be regulated by specific amino acids, tyrosine and phenylalanine. Defined
      deletion mutants in one or several peptide permeases were constructed and tested
      for their capacity to grow in peptide-containing medium. Among the four putative
      Opp systems, Opp-3 was the only system able to provide oligopeptides for growth,
      ranging in length from 3 to 8 amino acids. Dipeptides were imported exclusively
      by DtpT, a proton-driven di- and tripeptide permease. These data provide a first
      complete inventory of the peptide transport systems opp and dtpT of S. aureus.
      Among them, the newly identified Opp-3 appears to be the main Opp system
      supplying the cell with peptides as nutritional sources.

PMID- 17496097
TI  - Identification of regions critically affecting kinetics and allosteric regulation
      of the Escherichia coli ADP-glucose pyrophosphorylase by modeling and
      pentapeptide-scanning mutagenesis.
AB  - ADP-glucose pyrophosphorylase (ADP-Glc PPase) is the enzyme responsible for the
      regulation of bacterial glycogen synthesis. To perform a structure-function
      relationship study of the Escherichia coli ADP-Glc PPase enzyme, we studied the
      effects of pentapeptide insertions at different positions in the enzyme and
      analyzed the results with a homology model. We randomly inserted 15 bp in a
      plasmid with the ADP-Glc PPase gene. We obtained 140 modified plasmids with
      single insertions of which 21 were in the coding region of the enzyme. Fourteen
      of them generated insertions of five amino acids, whereas the other seven created
      a stop codon and produced truncations. Correlation of ADP-Glc PPase activity to
      these modifications validated the enzyme model. Six of the insertions and one
      truncation produced enzymes with sufficient activity for the E. coli cells to
      synthesize glycogen and stain in the presence of iodine vapor. These were in
      regions away from the substrate site, whereas the mutants that did not stain had
      alterations in critical areas of the protein. The enzyme with a pentapeptide
      insertion between Leu(102) and Pro(103) was catalytically competent but
      insensitive to activation. We postulate this region as critical for the
      allosteric regulation of the enzyme, participating in the communication between
      the catalytic and regulatory domains.

PMID- 17496098
TI  - Generation of a membrane potential by Lactococcus lactis through aerobic electron
      transport.
AB  - Lactococcus lactis, a facultative anaerobic lactic acid bacterium, is known to
      have an increased growth yield when grown aerobically in the presence of heme. We
      have now established the presence of a functional, proton motive force-generating
      electron transfer chain (ETC) in L. lactis under these conditions. Proton motive
      force generation in whole cells was measured using a fluorescent probe (3',3'
      dipropylthiadicarbocyanine), which is sensitive to changes in membrane potential
      (Delta psi). Wild-type cells, grown aerobically in the presence of heme,
      generated a Delta psi even in the presence of the F(1)-F(o) ATPase inhibitor N,N'
      dicyclohexylcarbodiimide, while a cytochrome bd-negative mutant strain (CydA
      Delta) did not. We also observed high oxygen consumption rates by membrane
      vesicles prepared from heme-grown cells, compared to CydA Delta cells, upon the
      addition of NADH. This demonstrates that NADH is an electron donor for the L.
      lactis ETC and demonstrates the presence of a membrane-bound NADH-dehydrogenase.
      Furthermore, we show that the functional respiratory chain is present throughout
      the exponential and late phases of growth.

PMID- 17496099
TI  - NrdR controls differential expression of the Escherichia coli ribonucleotide
      reductase genes.
AB  - Escherichia coli possesses class Ia, class Ib, and class III ribonucleotide
      reductases (RNR). Under standard laboratory conditions, the aerobic class Ia
      nrdAB RNR genes are well expressed, whereas the aerobic class Ib nrdEF RNR genes
      are poorly expressed. The class III RNR is normally expressed under
      microaerophilic and anaerobic conditions. In this paper, we show that the E. coli
      YbaD protein differentially regulates the expression of the three sets of genes.
      YbaD is a homolog of the Streptomyces NrdR protein. It is not essential for
      growth and has been renamed NrdR. Previously, Streptomyces NrdR was shown to
      transcriptionally regulate RNR genes by binding to specific 16-bp sequence
      motifs, NrdR boxes, located in the regulatory regions of its RNR operons. All
      three E. coli RNR operons contain two such NrdR box motifs positioned in their
      regulatory regions. The NrdR boxes are located near to or overlap with the
      promoter elements. DNA binding experiments showed that NrdR binds to each of the
      upstream regulatory regions. We constructed deletions in nrdR (ybaD) and showed
      that they caused high-level induction of transcription of the class Ib RNR genes
      but had a much smaller effect on induction of transcription of the class Ia and
      class III RNR genes. We propose a model for differential regulation of the RNR
      genes based on binding of NrdR to the regulatory regions. The model assumes that
      differences in the positions of the NrdR binding sites, and in the sequences of
      the motifs themselves, determine the extent to which NrdR represses the
      transcription of each RNR operon.

PMID- 17496101
TI  - A functional homing endonuclease in the Bacillus anthracis nrdE group I intron.
AB  - The essential Bacillus anthracis nrdE gene carries a self-splicing group I intron
      with a putative homing endonuclease belonging to the GIY-YIG family. Here, we
      show that the nrdE pre-mRNA is spliced and that the homing endonuclease cleaves
      an intronless nrdE gene 5 nucleotides (nt) upstream of the intron insertion site,
      producing 2-nt 3' extensions. We also show that the sequence required for
      efficient cleavage spans at least 4 bp upstream and 31 bp downstream of the
      cleaved coding strand. The position of the recognition sequence in relation to
      the cleavage position is as expected for a GIY-YIG homing endonuclease.
      Interestingly, nrdE genes from several other Bacillaceae were also susceptible to
      cleavage, with those of Bacillus cereus, Staphylococcus epidermidis (nrdE1), B.
      anthracis, and Bacillus thuringiensis serovar konkukian being better substrates
      than those of Bacillus subtilis, Bacillus lichenformis, and S. epidermidis
      (nrdE2). On the other hand, nrdE genes from Lactococcus lactis, Escherichia coli,
      Salmonella enterica serovar Typhimurium, and Corynebacterium ammoniagenes were
      not cleaved. Intervening sequences (IVSs) residing in protein-coding genes are
      often found in enzymes involved in DNA metabolism, and the ribonucleotide
      reductase nrdE gene is a frequent target for self-splicing IVSs. A comparison of
      nrdE genes from seven gram-positive low-G+C bacteria, two bacteriophages, and
      Nocardia farcinica showed five different insertion sites for self-splicing IVSs
      within the coding region of the nrdE gene.

PMID- 17496102
TI  - Target genes and DNA-binding sites of the response regulator PhoR from
      Corynebacterium glutamicum.
AB  - The two-component signal transduction system PhoRS of Corynebacterium glutamicum
      is involved in the phosphate (P(i)) starvation response. To analyze the binding
      of unphosphorylated and phosphorylated PhoR to the promoters of phosphate
      starvation-inducible (psi) genes, this response regulator and the kinase domain
      of its cognate sensor, PhoS (MBP-PhoSDelta1-246), were overproduced and purified.
      MBP-PhoSDelta1-246 showed constitutive autophosphorylation activity, and a rapid
      phosphoryl group transfer from phosphorylated MBP-PhoSDelta1-246 to PhoR was
      observed. Gel mobility shift assays revealed that phosphorylation increases the
      DNA-binding affinity of PhoR. The affinity of PhoR approximately P to different
      promoters varied and decreased in the order pstSCAB > phoRS > phoC > ushA > porB
      > ugpA > pitA > nucH and phoH1 > glpQ1. The binding sites in front of pstSCAB and
      phoRS were localized at positions -194 to -176 and -61 to -43 upstream of the
      transcriptional start sites, respectively. Alignment of these two 19-bp binding
      sites revealed a high identity in the 5'-terminal part, but not in the 3'
      terminal part. As many OmpR-type response regulators bind to direct repeats, the
      19-bp sequence might be interpreted as a loosely conserved 8-bp direct repeat
      separated by 3 bp. This idea was supported by the fact that the highest binding
      affinity was observed with a perfect 8-bp direct repeat of the sequence
      CCTGTGAAaatCCTGTGAA. Inspection of the other target promoters revealed sequences
      with some similarity to this binding motif, which might represent PhoR binding
      sites. The in vivo relevance of the PhoR-binding site within the phoRS promoter
      was supported by reporter gene studies.

PMID- 17496100
TI  - Horizontal gene transfer and homologous recombination drive the evolution of the
      nitrogen-fixing symbionts of Medicago species.
AB  - Using nitrogen-fixing Sinorhizobium species that interact with Medicago plants as
      a model system, we aimed at clarifying how sex has shaped the diversity of
      bacteria associated with the genus Medicago on the interspecific and
      intraspecific scales. To gain insights into the diversification of these
      symbionts, we inferred a topology that includes the different specificity groups
      which interact with Medicago species, based on sequences of the nodulation gene
      cluster. Furthermore, 126 bacterial isolates were obtained from two soil samples,
      using Medicago truncatula and Medicago laciniata as host plants, to study the
      differentiation between populations of Sinorhizobium medicae, Sinorhizobium
      meliloti bv. meliloti, and S. meliloti bv. medicaginis. The former two can be
      associated with M. truncatula (among other species of Medicago), whereas the last
      organism is the specific symbiont of M. laciniata. These bacteria were
      characterized using a multilocus sequence analysis of four loci, located on the
      chromosome and on the two megaplasmids of S. meliloti. The phylogenetic results
      reveal that several interspecific horizontal gene transfers occurred during the
      diversification of Medicago symbionts. Within S. meliloti, the analyses show that
      nod genes specific to different host plants have spread to different genetic
      backgrounds through homologous recombination, preventing further divergence of
      the different ecotypes. Thus, specialization to different host plant species does
      not prevent the occurrence of gene flow among host-specific biovars of S.
      meliloti, whereas reproductive isolation between S. meliloti bv. meliloti and S.
      medicae is maintained even though these bacteria can cooccur in sympatry on the
      same individual host plants.

PMID- 17496103
TI  - Evidence for modified mechanisms of chloroethene oxidation in Pseudomonas
      butanovora mutants containing single amino acid substitutions in the hydroxylase
      alpha-subunit of butane monooxygenase.
AB  - The properties of oxidation of dichloroethene (DCE) and trichloroethylene (TCE)
      by three mutant strains of Pseudomonas butanovora containing single amino acid
      substitutions in the alpha-subunit of butane monooxygenase hydroxylase (BMOH
      alpha) were compared to the properties of the wild-type strain (Rev WT). The
      rates of oxidation of three chloroethenes (CEs) were reduced in mutant strain
      G113N and corresponded with a lower maximum rate of butane oxidation. The rate of
      TCE degradation was reduced by one-half in mutant strain L279F, whereas the rates
      of DCE oxidation were the same as those in Rev WT. Evidence was obtained that the
      composition of products of CE oxidation differed between Rev WT and some of the
      mutant strains. For example, while Rev WT released nearly all available chlorine
      stoichiometrically during CE oxidation, strain F321Y released about 40% of the
      chlorine during 1,2-cis-DCE and TCE oxidation, and strain G113N released between
      14 and 25% of the available chlorine during oxidation of DCE and 56% of the
      available chlorine during oxidation of TCE. Whereas Rev WT, strain L279F, and
      strain F321Y formed stoichiometric amounts of 1,2-cis-DCE epoxide during
      oxidation of 1,2-cis-DCE, only about 50% of the 1,2-cis-DCE oxidized by strain
      G113N was detected as the epoxide. Evidence was obtained that 1,2-cis-DCE epoxide
      was a substrate for butane monooxygenase (BMO) that was oxidized after the parent
      compound was consumed. Yet all of the mutant strains released less than 40% of
      the available 1,2-cis-DCE chlorine, suggesting that they have altered activity
      towards the epoxide. In addition, strain G113N was unable to degrade the epoxide.
      TCE epoxide was detected during exposure of Rev WT and strain F321Y to TCE but
      was not detected with strains L279F and G113N. Lactate-dependent O(2) uptake
      rates were differentially affected by DCE degradation in the mutant strains,
      providing evidence that some products released by the altered BMOs reduced the
      impact of CE on cellular toxicity. The use of CEs as substrates in combination
      with P. butanovora BMOH-alpha mutants might allow insights into the catalytic
      mechanism of BMO to be obtained.

PMID- 17496104
TI  - The Haemophilus influenzae hFbpABC Fe3+ transporter: analysis of the membrane
      permease and development of a gallium-based screen for mutants.
AB  - The obligate human pathogen Haemophilus influenzae utilizes a siderophore
      independent (free) Fe(3+) transport system to obtain this essential element from
      the host iron-binding protein transferrin. The hFbpABC transporter is a binding
      protein-dependent ABC transporter that functions to shuttle (free) Fe(3+) through
      the periplasm and across the inner membrane of H. influenzae. This investigation
      focuses on the structure and function of the hFbpB membrane permease component of
      the transporter, a protein that has eluded prior characterization. Based on
      multiple-sequence alignments between permease orthologs, a series of site
      directed mutations targeted at residues within the two conserved permease motifs
      were generated. The hFbpABC transporter was expressed in a siderophore-deficient
      Escherichia coli background, and effects of mutations were analyzed using growth
      rescue and radiolabeled (55)Fe(3+) transport assays. Results demonstrate that
      mutation of the invariant glycine (G418A) within motif 2 led to attenuated
      transport activity, while mutation of the invariant glycine (G155A/V/E) within
      motif 1 had no discernible effect on activity. Individual mutations of well
      conserved leucines (L154D and L417D) led to attenuated and null transport
      activities, respectively. As a complement to site-directed methods, a mutant
      screen based on resistance to the toxic iron analog gallium, an hFbpABC
      inhibitor, was devised. The screen led to the identification of several
      significant hFbpB mutations; V497I, I174F, and S475I led to null transport
      activities, while S146Y resulted in attenuated activity. Significant residues
      were mapped to a topological model of the hFbpB permease, and the implications of
      mutations are discussed in light of structural and functional data from related
      ABC transporters.

PMID- 17496105
TI  - Phosphatidylinositol 4-kinase activation is an early response to salicylic acid
      in Arabidopsis suspension cells.
AB  - Salicylic acid (SA) has a central role in defense against pathogen attack. In
      addition, its role in such diverse processes as germination, flowering,
      senescence, and thermotolerance acquisition has been documented. However, little
      is known about the early signaling events triggered by SA. Using Arabidopsis
      (Arabidopsis thaliana) suspension cells as a model, it was possible to show by in
      vivo metabolic phospholipid labeling with (33)P(i) that SA addition induced a
      rapid and early (in few minutes) decrease in a pool of phosphatidylinositol (PI).
      This decrease paralleled an increase in PI 4-phosphate and PI 4,5-bisphosphate.
      These changes could be inhibited by two different inhibitors of type III PI 4
      kinases, phenylarsine oxide and 30 microm wortmannin; no inhibitory effect was
      seen with 1 microm wortmannin, a concentration inhibiting PI 3-kinases but not PI
      4-kinases. We therefore undertook a study of the effects of wortmannin on SA
      responsive transcriptomes. Using the Complete Arabidopsis Transcriptome
      MicroArray chip, we could identify 774 genes differentially expressed upon SA
      treatment. Strikingly, among these genes, the response to SA of 112 of them was
      inhibited by 30 microm wortmannin, but not by 1 microm wortmannin.

PMID- 17496106
TI  - Distinct expression patterns of natural antisense transcripts in Arabidopsis.
AB  - It has been shown that overlapping cis-natural antisense transcripts (cis-NATs)
      can form a regulatory circuit in which small RNAs derived from one transcript
      regulate stability of the other transcript, which manifests itself as
      anticorrelated expression. However, little is known about how widespread
      antagonistic expression of cis-NATs is. We have determined how frequently cis-NAT
      pairs, which make up 7.4% of annotated transcription units in the Arabidopsis
      (Arabidopsis thaliana) genome, show anticorrelated expression patterns. Indeed,
      global expression profiles of pairs of cis-NATs on average have significantly
      lower pairwise Pearson correlation coefficients than other pairs of neighboring
      genes whose transcripts do not overlap. However, anticorrelated expression that
      is greater than expected by chance is found in only a small number of cis-NAT
      pairs. The degree of anticorrelation does not depend on the length of the overlap
      or on the distance of the 5' ends of the transcripts. Consistent with earlier
      findings, cis-NATs do not exhibit an increased likelihood to give rise to small
      RNAs, as determined from available small RNA sequences and massively parallel
      signature sequencing tags. However, the overlapping regions of cis-NATs appeared
      to be enriched for small RNA loci compared to nonoverlapping regions.
      Furthermore, expression of cis-NATs was not disproportionately affected in
      various RNA-silencing mutants. Our results demonstrate that there is a trend
      toward anticorrelated expression of cis-NAT pairs in Arabidopsis, but currently
      available data do not produce a strong signature of small RNA-mediated silencing
      for this process.

PMID- 17496107
TI  - Monoacylglycerols are components of root waxes and can be produced in the aerial
      cuticle by ectopic expression of a suberin-associated acyltransferase.
AB  - The interface between plants and the environment is provided for aerial organs by
      epicuticular waxes that have been extensively studied. By contrast, little is
      known about the nature, biosynthesis, and role of waxes at the root-rhizosphere
      interface. Waxes isolated by rapid immersion of Arabidopsis (Arabidopsis
      thaliana) roots in organic solvents were rich in saturated C18-C22 alkyl esters
      of p-hydroxycinnamic acids, but also contained significant amounts of both alpha-
      and beta-isomers of monoacylglycerols with C22 and C24 saturated acyl groups and
      the corresponding free fatty acids. Production of these compounds in root waxes
      was positively correlated to the expression of sn-glycerol-3-P acyltransferase5
      (GPAT5), a gene encoding an acyltransferase previously shown to be involved in
      aliphatic suberin synthesis. This suggests a direct metabolic relationship
      between suberin and some root waxes. Furthermore, when ectopically expressed in
      Arabidopsis, GPAT5 produced very-long-chain saturated monoacylglycerols and free
      fatty acids as novel components of cuticular waxes. The crystal morphology of
      stem waxes was altered and the load of total stem wax compounds was doubled,
      although the major components typical of the waxes found on wild-type plants
      decreased. These results strongly suggest that GPAT5 functions in vivo as an
      acyltransferase to a glycerol-containing acceptor and has access to the same pool
      of acyl intermediates and/or may be targeted to the same membrane domain as that
      of wax synthesis in aerial organs.

PMID- 17496108
TI  - Deletion of glycine decarboxylase in Arabidopsis is lethal under
      nonphotorespiratory conditions.
AB  - The mitochondrial multienzyme glycine decarboxylase (GDC) catalyzes the
      tetrahydrofolate-dependent catabolism of glycine to 5,10-methylene
      tetrahydrofolate and the side products NADH, CO(2), and NH(3). This reaction
      forms part of the photorespiratory cycle and contributes to one-carbon
      metabolism. While the important role of GDC for these two metabolic pathways is
      well established, the existence of bypassing reactions has also been suggested.
      Therefore, it is not clear to what extent GDC is obligatory for these processes.
      Here, we report on features of individual and combined T-DNA insertion mutants
      for one of the GDC subunits, P protein, which is encoded by two genes in
      Arabidopsis (Arabidopsis thaliana). The individual knockout of either of these
      two genes does not significantly alter metabolism and photosynthetic performance
      indicating functional redundancy. In contrast, the double mutant does not develop
      beyond the cotyledon stage in air enriched with 0.9% CO(2). Rosette leaves do not
      appear and the seedlings do not survive for longer than about 3 to 4 weeks under
      these nonphotorespiratory conditions. This feature distinguishes the GDC-lacking
      double mutant from all other known photorespiratory mutants and provides evidence
      for the nonreplaceable function of GDC in vital metabolic processes other than
      photorespiration.

PMID- 17496109
TI  - High-throughput, high-sensitivity analysis of gene expression in Arabidopsis.
AB  - High-throughput gene expression analysis of genes expressed during salt stress
      was performed using a novel multiplexed quantitative nuclease protection assay
      that involves customized DNA microarrays printed within the individual wells of
      96-well plates. The levels of expression of the transcripts from 16 different
      genes were quantified within crude homogenates prepared from Arabidopsis
      (Arabidopsis thaliana) plants also grown in a 96-well plate format. Examples are
      provided of the high degree of reproducibility of quantitative dose-response data
      and of the sensitivity of detection of changes in gene expression within limiting
      amounts of tissue. The lack of requirement for RNA purification renders the assay
      particularly suited for high-throughput gene expression analysis and for the
      discovery of novel chemical compounds that specifically modulate the expression
      of endogenous target genes.

PMID- 17496110
TI  - Comparative cross-species alternative splicing in plants.
AB  - Alternative splicing (AS) can add significantly to genome complexity. Plants are
      thought to exhibit less AS than animals. An algorithm, based on expressed
      sequence tag (EST) pairs gapped alignment, was developed that takes advantage of
      the relatively small intron and exon size in plants and directly compares pairs
      of ESTs to search for AS. EST pairs gapped alignment was first evaluated in
      Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and tomato (Solanum
      lycopersicum) for which annotated genome sequence is available and was shown to
      accurately predict splicing events. The method was then applied to 11 plant
      species that include 17 cultivars for which enough ESTs are available. The
      results show a large, 3.7-fold difference in AS rates between plant species with
      Arabidopsis and rice in the lower range and lettuce (Lactuca sativa) and sorghum
      (Sorghum bicolor) in the upper range. Hence, compared to higher animals, plants
      show a much greater degree of variety in their AS rates and in some plant species
      the rates of animal and plant AS are comparable although the distribution of AS
      types may differ. In eudicots but not monocots, a correlation between genome size
      and AS rates was detected, implying that in eudicots the mechanisms that lead to
      larger genomes are a driving force for the evolution of AS.

PMID- 17496111
TI  - The Flaveria bidentis beta-carbonic anhydrase gene family encodes cytosolic and
      chloroplastic isoforms demonstrating distinct organ-specific expression patterns.
AB  - Carbonic anhydrase (CA) catalyzes the interconversion of CO(2) and bicarbonate,
      the forms of inorganic carbon used by the primary carboxylating enzymes of C(3)
      and C(4) plants, respectively. Multiple forms of CA are found in both
      photosynthetic subtypes; however, the number of isoforms and the location and
      function of each have not been elucidated for any single plant species. Genomic
      Southern analyses showed that the C(4) dicotyledon Flaveria bidentis 'Kuntze'
      contains a small gene family encoding beta-CA and cDNAs encoding three distinct
      beta-CAs, named CA1, CA2, and CA3, were isolated. Quantitative reverse
      transcription-polymerase chain reactions showed that each member of this beta-CA
      family has a specific expression pattern in F. bidentis leaves, roots, and
      flowers. CA3 transcripts were at least 50 times more abundant than CA2 or CA1
      transcripts in leaves. CA2 transcripts were detected in all organs examined and
      were the most abundant CA transcripts in roots. CA1 mRNA levels were similar to
      those of CA2 in leaves, but were considerably lower in roots and flowers. In
      vitro import assays showed CA1 was imported into isolated pea (Pisum sativum)
      chloroplasts, whereas CA2 and CA3 were not. These results support the following
      roles for F. bidentis CAs: CA3 is responsible for catalyzing the first step in
      the C(4) pathway in the mesophyll cell cytosol; CA2 provides bicarbonate for
      anapleurotic reactions involving nonphotosynthetic forms of phosphoenolpyruvate
      carboxylase in the cytosol of cells in both photosynthetic and nongreen tissues;
      and CA1 carries out nonphotosynthetic functions demonstrated by C(3)
      chloroplastic beta-CAs, including lipid biosynthesis and antioxidant activity.

PMID- 17496112
TI  - Identification of a bipartite jasmonate-responsive promoter element in the
      Catharanthus roseus ORCA3 transcription factor gene that interacts specifically
      with AT-Hook DNA-binding proteins.
AB  - Jasmonates are plant signaling molecules that play key roles in defense against
      certain pathogens and insects, among others, by controlling the biosynthesis of
      protective secondary metabolites. In Catharanthus roseus, the APETALA2-domain
      transcription factor ORCA3 is involved in the jasmonate-responsive activation of
      terpenoid indole alkaloid biosynthetic genes. ORCA3 gene expression is itself
      induced by jasmonate. By loss- and gain-of-function experiments, we located a 74
      bp region within the ORCA3 promoter, which contains an autonomous jasmonate
      responsive element (JRE). The ORCA3 JRE is composed of two important sequences: a
      quantitative sequence responsible for a high level of expression and a
      qualitative sequence that appears to act as an on/off switch in response to
      methyl jasmonate. We isolated 12 different DNA-binding proteins having one of
      four different types of DNA-binding domains, using the ORCA3 JRE as bait in a
      yeast (Saccharomyces cerevisiae) one-hybrid transcription factor screening. The
      binding of one class of proteins bearing a single AT-hook DNA-binding motif was
      affected by mutations in the quantitative sequence within the JRE. Two of the AT
      hook proteins tested had a weak activating effect on JRE-mediated reporter gene
      expression, suggesting that AT-hook family members may be involved in determining
      the level of expression of ORCA3 in response to jasmonate.

PMID- 17496113
TI  - Hawaiian skirt: an F-box gene that regulates organ fusion and growth in
      Arabidopsis.
AB  - A fast neutron-mutagenized population of Arabidopsis (Arabidopsis thaliana)
      Columbia-0 wild-type plants was screened for floral phenotypes and a novel
      mutant, termed hawaiian skirt (hws), was identified that failed to shed its
      reproductive organs. The mutation is the consequence of a 28 bp deletion that
      introduces a premature amber termination codon into the open reading frame of a
      putative F-box protein (At3g61590). The most striking anatomical characteristic
      of hws plants is seen in flowers where individual sepals are fused along the
      lower part of their margins. Crossing of the abscission marker, Pro(PGAZAT):beta
      glucuronidase, into the mutant reveals that while floral organs are retained it
      is not the consequence of a failure of abscission zone cells to differentiate.
      Anatomical analysis indicates that the fusion of sepal margins precludes shedding
      even though abscission, albeit delayed, does occur. Spatial and temporal
      characterization, using Pro(HWS):beta-glucuronidase or Pro(HWS):green fluorescent
      protein fusions, has identified HWS expression to be restricted to the stele and
      lateral root cap, cotyledonary margins, tip of the stigma, pollen, abscission
      zones, and developing seeds. Comparative phenotypic analyses performed on the hws
      mutant, Columbia-0 wild type, and Pro(35S):HWS ectopically expressing lines has
      revealed that loss of HWS results in greater growth of both aerial and below
      ground organs while overexpressing the gene brings about a converse effect. These
      observations are consistent with HWS playing an important role in regulating
      plant growth and development.

PMID- 17496114
TI  - Patterns of selection and tissue-specific expression among maize domestication
      and crop improvement loci.
AB  - The domestication of maize (Zea mays sp. mays) from its wild progenitors
      represents an opportunity to investigate the timing and genetic basis of
      morphological divergence resulting from artificial selection on target genes. We
      compared sequence diversity of 30 candidate selected and 15 reference loci
      between the three populations of wild teosintes, maize landraces, and maize
      inbred lines. We inferred an approximately equal ratio of genes selected during
      early domestication and genes selected during modern crop breeding. Using an
      expanded dataset of 48 candidate selected and 658 neutral reference loci, we
      tested the hypothesis that candidate selected genes in maize are more likely to
      have transcriptional functions than neutral reference genes, but there was no
      overrepresentation of regulatory genes in the selected gene dataset. Electronic
      northern analysis revealed that candidate genes are significantly overexpressed
      in the maize ear relative to vegetative tissues such as maize shoot, leaf, and
      root tissue. The maize ear underwent dramatic morphological alteration upon
      domestication and has been a continuing target of selection for maize yield.
      Therefore, we hypothesize that genes targeted by selection are more likely to be
      expressed in tissues that experienced high levels of morphological divergence
      during domestication and crop improvement.

PMID- 17496115
TI  - Pentraxin 3 is elevated in haemodialysis patients and is associated with
      cardiovascular disease.
AB  - BACKGROUND: Pentraxins are mediators of inflammation as well as markers of the
      acute-phase reaction. While elevation of C-reactive protein (CRP) in patients
      with renal failure and its association with cardiovascular disease is well
      described, there are no data on pentraxin 3 (PTX3) in this population. METHODS:
      Plasma was obtained from 44 chronic haemodialysis (HD) patients, 35 peritoneal
      dialysis (PD) patients, 39 patients with chronic renal failure (CRF) not on
      dialysis therapy and 14 age-matched normal subjects. PTX3 production in whole
      blood was also investigated in samples taken before and during HD. RESULTS: PTX3
      plasma levels were significantly higher in HD patients (5.8 +/- 0.6 ng/ml)
      compared with the other three groups. There were no significant differences
      between PD patients (1.5 +/- 0.4 ng/ml), CRF patients (1.5 +/- 0.4 ng/ml) and
      normal subjects (0.76 +/- 0.2 ng/ml). In dialysis patients, PTX3 levels
      correlated significantly with time on renal replacement therapy (RRT) and with
      weekly erythropoietin dose. PTX3 levels were significantly higher in patients
      with coronary artery disease and peripheral artery disease compared with those
      without. During a single HD session, PTX3 production was higher in whole blood
      samples taken after 3 h HD compared with samples taken before HD. CONCLUSIONS:
      PTX3 levels are markedly elevated in HD patients. The increase in PTX3 production
      in whole blood after HD indicates that the HD procedure itself contributes to
      elevated PTX3 levels in HD patients. The association between PTX3 and
      cardiovascular morbidity suggests a possible connection of PTX3 with
      atherosclerosis and cardiovascular disease in HD patients.

PMID- 17496116
TI  - Increasing plasma membrane phosphatidylinositol(4,5)bisphosphate biosynthesis
      increases phosphoinositide metabolism in Nicotiana tabacum.
AB  - A genetic approach was used to increase phosphatidylinositol(4,5)bisphosphate
      [PtdIns(4,5)P2] biosynthesis and test the hypothesis that PtdInsP kinase (PIPK)
      is flux limiting in the plant phosphoinositide (PI) pathway. Expressing human
      PIPKIalpha in tobacco (Nicotiana tabacum) cells increased plasma membrane
      PtdIns(4,5)P2 100-fold. In vivo studies revealed that the rate of 32Pi
      incorporation into whole-cell PtdIns(4,5)P2 increased >12-fold, and the ratio of
      [3H]PtdInsP2 to [3H]PtdInsP increased 6-fold, but PtdInsP levels did not
      decrease, indicating that PtdInsP biosynthesis was not limiting. Both
      [3H]inositol trisphosphate and [3H]inositol hexakisphosphate increased 3-and 1.5
      fold, respectively, in the transgenic lines after 18 h of labeling. The
      inositol(1,4,5)trisphosphate [Ins(1,4,5)P3] binding assay showed that total
      cellular Ins(1,4,5)P3/g fresh weight was >40-fold higher in transgenic tobacco
      lines; however, even with this high steady state level of Ins(1,4,5)P3, the
      pathway was not saturated. Stimulating transgenic cells with hyperosmotic stress
      led to another 2-fold increase, suggesting that the transgenic cells were in a
      constant state of PI stimulation. Furthermore, expressing Hs PIPKIalpha increased
      sugar use and oxygen uptake. Our results demonstrate that PIPK is flux limiting
      and that this high rate of PI metabolism increased the energy demands in these
      cells.

PMID- 17496117
TI  - G-boxes, bigfoot genes, and environmental response: characterization of
      intragenomic conserved noncoding sequences in Arabidopsis.
AB  - A tetraploidy left Arabidopsis thaliana with 6358 pairs of homoeologs that, when
      aligned, generated 14,944 intragenomic conserved noncoding sequences (CNSs). Our
      previous work assembled these phylogenetic footprints into a database. We show
      that known transcription factor (TF) binding motifs, including the G-box, are
      overrepresented in these CNSs. A total of 254 genes spanning long lengths of CNS
      rich chromosomes (Bigfoot) dominate this database. Therefore, we made
      subdatabases: one containing Bigfoot genes and the other containing genes with
      three to five CNSs (Smallfoot). Bigfoot genes are generally TFs that respond to
      signals, with their modal CNS positioned 3.1 kb 5' from the ATG. Smallfoot genes
      encode components of signal transduction machinery, the cytoskeleton, or involve
      transcription. We queried each subdatabase with each possible 7-nucleotide
      sequence. Among hundreds of hits, most were purified from CNSs, and almost all of
      those significantly enriched in CNSs had no experimental history. The 7-mers in
      CNSs are not 5'- to 3'-oriented in Bigfoot genes but are often oriented in
      Smallfoot genes. CNSs with one G-box tend to have two G-boxes. CNSs were shared
      with the homoeolog only and with no other gene, suggesting that binding site
      turnover impedes detection. Bigfoot genes may function in adaptation to
      environmental change.

PMID- 17496118
TI  - The two AGPase subunits evolve at different rates in angiosperms, yet they are
      equally sensitive to activity-altering amino acid changes when expressed in
      bacteria.
AB  - The rate of protein evolution is generally thought to reflect, at least in part,
      the proportion of amino acids within the protein that are needed for proper
      function. In the case of ADP-glucose pyrophosphorylase (AGPase), this premise led
      to the hypothesis that, because the AGPase small subunit is more conserved
      compared with the large subunit, a higher proportion of the amino acids of the
      small subunit are required for enzyme activity compared with the large subunit.
      Evolutionary analysis indicates that the AGPase small subunit has been subject to
      more intense purifying selection than the large subunit in the angiosperms.
      However, random mutagenesis and expression of the maize (Zea mays) endosperm
      AGPase in bacteria show that the two AGPase subunits are equally predisposed to
      enzyme activity-altering amino acid changes when expressed in one environment
      with a single complementary subunit. As an alternative hypothesis, we suggest
      that the small subunit exhibits more evolutionary constraints in planta than does
      the large subunit because it is less tissue specific and thus must form
      functional enzyme complexes with different large subunits. Independent approaches
      provide data consistent with this alternative hypothesis.

PMID- 17496119
TI  - UDP-glucose 4-epimerase isoforms UGE2 and UGE4 cooperate in providing UDP
      galactose for cell wall biosynthesis and growth of Arabidopsis thaliana.
AB  - Five Arabidopsis thaliana genes that encode UDP-glucose 4-epimerase (UGE) and
      represent two ancient plant UGE clades might be involved in the regulation of
      cell wall carbohydrate biosynthesis. We tested this hypothesis in a genome-wide
      reverse genetic study. Despite significant contributions of each gene to total
      UGE activity, none was essential for normal growth on soil. uge2 uge4 displayed
      dramatic general growth defects, while other mutant combinations were partially
      aberrant. UGE2 together with UGE3 influenced pollen development. UGE2 and UGE4
      synergistically influenced cell wall galactose content, which was correlated with
      shoot growth. UGE2 strongly and UGE1 and UGE5 lightly supported UGE4 in
      influencing root growth and cell wall galactose content by affecting galactan
      content. By contrast, only UGE4 influenced xyloglucan galactosylation in roots.
      Secondary hypocotyl thickening and arabinogalactan protein carbohydrate structure
      in xylem parenchyma depended on the combination of UGE2 and UGE4. As opposed to
      cell wall galactose content, tolerance to external galactose strictly paralleled
      total UGE activity. We suggest a gradual recruitment of individual UGE isoforms
      into specific roles. UGE2 and UGE4 influence growth and cell wall carbohydrate
      biosynthesis throughout the plant, UGE3 is specialized for pollen development,
      and UGE1 and UGE5 might act in stress situations.

PMID- 17496120
TI  - TIME FOR COFFEE encodes a nuclear regulator in the Arabidopsis thaliana circadian
      clock.
AB  - The plant circadian clock is required for daily anticipation of the diurnal
      environment. Mutation in Arabidopsis thaliana TIME FOR COFFEE (TIC) affects free
      running circadian rhythms. To investigate how TIC functions within the circadian
      system, we introduced markers for the evening and morning phases of the clock
      into tic and measured evident rhythms. The phases of evening clock genes in tic
      were all advanced under light/dark cycles without major expression level defects.
      With regard to morning-acting genes, we unexpectedly found that TIC has a closer
      relationship with LATE ELONGATED HYPOCOTYL (LHY) than with CIRCADIAN CLOCK
      ASSOCIATED1, as tic has a specific LHY expression level defect. Epistasis
      analysis demonstrated that there were no clear rhythms in double mutants of tic
      and evening-acting clock genes, although double mutants of tic and morning-acting
      genes exhibited a similar free-running period as tic. We isolated TIC and found
      that its mRNA expression is continuously present over the diurnal cycle, and the
      encoded protein appears to be strictly localized to the nucleus. Neither its
      abundance nor its cellular distribution was found to be clock regulated. We
      suggest that TIC encodes a nucleus-acting clock regulator working close to the
      central oscillator.

PMID- 17496121
TI  - CYP703 is an ancient cytochrome P450 in land plants catalyzing in-chain
      hydroxylation of lauric acid to provide building blocks for sporopollenin
      synthesis in pollen.
AB  - CYP703 is a cytochrome P450 family specific to land plants. Typically, each plant
      species contains a single CYP703. Arabidopsis thaliana CYP703A2 is expressed in
      the anthers of developing flowers. Expression is initiated at the tetrad stage
      and restricted to microspores and to the tapetum cell layer. Arabidopsis CYP703A2
      knockout lines showed impaired pollen development and a partial male-sterile
      phenotype. Scanning electron and transmission electron microscopy of pollen from
      the knockout plants showed impaired pollen wall development with absence of
      exine. The fluorescent layer around the pollen grains ascribed to the presence of
      phenylpropanoid units in sporopollenin was absent in the CYP703A2 knockout lines.
      Heterologous expression of CYP703A2 in yeast cells demonstrated that CYP703
      catalyzes the conversion of medium-chain saturated fatty acids to the
      corresponding monohydroxylated fatty acids, with a preferential hydroxylation of
      lauric acid at the C-7 position. Incubation of recombinant CYP703 with methanol
      extracts from developing flowers confirmed that lauric acid and in-chain hydroxy
      lauric acids are the in planta substrate and product, respectively. These data
      demonstrate that in-chain hydroxy lauric acids are essential building blocks in
      sporopollenin synthesis and enable the formation of ester and ether linkages with
      phenylpropanoid units. This study identifies CYP703 as a P450 family specifically
      involved in pollen development.

PMID- 17496122
TI  - Arabidopsis VIRE2 INTERACTING PROTEIN2 is required for Agrobacterium T-DNA
      integration in plants.
AB  - Agrobacterium tumefaciens-mediated genetic transformation is an efficient tool
      for genetic engineering of plants. VirE2 is a single-stranded DNA binding
      Agrobacterium protein that is transported into the plant cell and presumably
      protects the T-DNA from degradation. Using a yeast two-hybrid system, we
      identified Arabidopsis thaliana VIRE2-INTERACTING PROTEIN2 (VIP2) with a NOT
      domain that is conserved in both plants and animals. Furthermore, we provide
      evidence supporting VIP2 interaction with VIP1, a basic domain/leucine zipper
      motif-containing protein required for nuclear import and integration of T-DNA.
      Virus-induced gene silencing of VIP2 in Nicotiana benthamiana and
      characterization of the Arabidopsis vip2 mutant (At vip2) demonstrate that VIP2
      is required for Agrobacterium-mediated stable transformation but not for
      transient transformation. Assays based upon a promoter-trap vector and
      quantification of T-DNA integration further confirmed VIP2 involvement in T-DNA
      integration. Interestingly, VIP2 transcripts were induced to a greater extent
      over prolonged periods after infection with a T-DNA transfer-competent
      Agrobacterium strain compared with the transfer-deficient Agrobacterium strain.
      Transcriptome analyses of At vip2 suggest that VIP2 is likely a transcriptional
      regulator, and the recalcitrancy to transformation in At vip2 is probably due to
      the combination of muted gene expression response upon Agrobacterium infection
      and repression of histone genes resulting in decreased T-DNA integration events.

PMID- 17496123
TI  - The Schizosaccharomyces pombe Cdc7 protein kinase required for septum formation
      is a client protein of Cdc37.
AB  - Cdc37 is an essential molecular chaperone found in fungi and metazoa whose main
      specificity is for certain protein kinases. Cdc37 can act as an Hsp90 cochaperone
      or alone; in yeasts, the interaction with Hsp90 is weak and appears not to be
      essential for Cdc37 function. Numerous genetic interactions between Cdc37 and
      likely client proteins have been observed in yeasts, but biochemical confirmation
      has been reported in only a few cases. We and others have generated and
      characterized temperature-sensitive cdc37 alleles in S. pombe and have used them
      to investigate the cellular roles of Cdc37: previous work has shown that mitotic
      Cdc2 is a major client. In this paper, we describe a screen for mutations
      synthetically lethal with a cdc37ts mutant with the aim of identifying genes
      encoding further client proteins of Cdc37. Ten such strains were isolated, and
      genomic libraries were screened for rescuing plasmids. In one case, a truncated
      cdc7 gene was identified. Further experiments showed that the mutation in this
      strain was indeed in cdc7. Cdc7 is a protein kinase required for septum
      initiation, and we show that its kinase activity is greatly reduced when Cdc37
      function is impaired. Cdc7 normally locates to the spindle pole body during
      mitosis, and this appears to be unaffected in the cdc37ts mutant. Other evidence
      suggests that, in addition to mitosis and septum initiation, Cdc37 may also be
      required for septum cleavage.

PMID- 17496124
TI  - Development and application of a green fluorescent protein sentinel system for
      identification of RNA interference in Blastomyces dermatitidis illuminates the
      role of septin in morphogenesis and sporulation.
AB  - A high-throughput strategy for testing gene function would accelerate progress in
      our understanding of disease pathogenesis for the dimorphic fungus Blastomyces
      dermatitidis, whose genome is being completed. We developed a green fluorescent
      protein (GFP) sentinel system of gene silencing to rapidly study genes of unknown
      function. Using Gateway technology to efficiently generate RNA interference
      plasmids, we cloned a target gene, "X," next to GFP to create one hairpin to
      knock down the expression of both genes so that diminished GFP reports target
      gene expression. To test this approach in B. dermatitidis, we first used LACZ and
      the virulence gene BAD1 as targets. The level of GFP reliably reported
      interference of their expression, leading to rapid detection of gene-silenced
      transformants. We next investigated a previously unstudied gene encoding septin
      and explored its possible role in morphogenesis and sporulation. A CDC11 septin
      homolog in B. dermatitidis localized to the neck of budding yeast cells. CDC11
      silenced transformants identified with the sentinel system grew slowly as flat or
      rough colonies on agar. Microscopically, they formed ballooned, distorted yeast
      cells that failed to bud, and they sporulated poorly as mold. Hence, this GFP
      sentinel system enables rapid detection of gene silencing and has revealed a
      pronounced role for septin in morphogenesis, budding, and sporulation of B.
      dermatitidis.

PMID- 17496125
TI  - Two novel, putatively cell wall-associated and glycosylphosphatidylinositol
      anchored alpha-glucanotransferase enzymes of Aspergillus niger.
AB  - In the genome sequence of Aspergillus niger CBS 513.88, three genes were
      identified with high similarity to fungal alpha-amylases. The protein sequences
      derived from these genes were different in two ways from all described fungal
      alpha-amylases: they were predicted to be glycosylphosphatidylinositol anchored,
      and some highly conserved amino acids of enzymes in the alpha-amylase family were
      absent. We expressed two of these enzymes in a suitable A. niger strain and
      characterized the purified proteins. Both enzymes showed transglycosylation
      activity on donor substrates with alpha-(1,4)-glycosidic bonds and at least five
      anhydroglucose units. The enzymes, designated AgtA and AgtB, produced new alpha
      (1,4)-glycosidic bonds and therefore belong to the group of the 4-alpha
      glucanotransferases (EC 2.4.1.25). Their reaction products reached a degree of
      polymerization of at least 30. Maltose and larger maltooligosaccharides were the
      most efficient acceptor substrates, although AgtA also used small
      nigerooligosaccharides containing alpha-(1,3)-glycosidic bonds as acceptor
      substrate. An agtA knockout of A. niger showed an increased susceptibility
      towards the cell wall-disrupting compound calcofluor white, indicating a cell
      wall integrity defect in this strain. Homologues of AgtA and AgtB are present in
      other fungal species with alpha-glucans in their cell walls, but not in yeast
      species lacking cell wall alpha-glucan. Possible roles for these enzymes in the
      synthesis and/or maintenance of the fungal cell wall are discussed.

PMID- 17496126
TI  - Host factors that control long terminal repeat retrotransposons in Saccharomyces
      cerevisiae: implications for regulation of mammalian retroviruses.

PMID- 17496127
TI  - Localization of RHO-4 indicates differential regulation of conidial versus
      vegetative septation in the filamentous fungus Neurospora crassa.
AB  - Rho-4 mutants of the filamentous fungus Neurospora crassa lack septa and asexual
      spores (conidia) and grow slowly. In this report, localization of green
      fluorescent protein-tagged RHO-4 is used to elucidate the differences in factors
      controlling RHO-4 localization during vegetative growth versus asexual
      development. RHO-4 forms a ring at incipient vegetative septation sites that
      constricts with the formation of the septum toward the septal pore; RHO-4
      persists around the septal pore after septum completion. During the formation of
      conidia, RHO-4 localizes to the primary septum but subsequently is relocalized to
      the cytoplasm after the placement of the secondary septum. Cytoplasmic
      localization and inactivation of RHO-4 are mediated by a direct physical
      interaction with RDI-1, a RHO guanosine nucleotide dissociation inhibitor.
      Inappropriate activation of the cyclic AMP-dependent protein kinase A pathway
      during vegetative growth causes mislocalization of RHO-4 away from septa to the
      cytoplasm, a process which was dependent upon RDI-1. An adenylate cyclase cr-1
      mutant partially suppresses the aconidial defect of rho-4 mutants but only rarely
      suppresses the vegetative septation defect, indicating that conidial septation is
      negatively regulated by CR-1. These data highlight the differences in the
      regulation of septation during conidiation versus vegetative septation in
      filamentous fungi.

PMID- 17496128
TI  - High-level production of beta-carotene in Saccharomyces cerevisiae by successive
      transformation with carotenogenic genes from Xanthophyllomyces dendrorhous.
AB  - To determine whether Saccharomyces cerevisiae can serve as a host for efficient
      carotenoid and especially beta-carotene production, carotenogenic genes from the
      carotenoid-producing yeast Xanthophyllomyces dendrorhous were introduced and
      overexpressed in S. cerevisiae. Because overexpression of these genes from an
      episomal expression vector resulted in unstable strains, the genes were
      integrated into genomic DNA to yield stable, carotenoid-producing S. cerevisiae
      cells. Furthermore, carotenoid production levels were higher in strains
      containing integrated carotenogenic genes. Overexpression of crtYB (which encodes
      a bifunctional phytoene synthase and lycopene cyclase) and crtI (phytoene
      desaturase) from X. dendrorhous was sufficient to enable carotenoid production.
      Carotenoid production levels were increased by additional overexpression of a
      homologous geranylgeranyl diphosphate (GGPP) synthase from S. cerevisiae that is
      encoded by BTS1. Combined overexpression of crtE (heterologous GGPP synthase)
      from X. dendrorhous with crtYB and crtI and introduction of an additional copy of
      a truncated 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene (tHMG1) into
      carotenoid-producing cells resulted in a successive increase in carotenoid
      production levels. The strains mentioned produced high levels of intermediates of
      the carotenogenic pathway and comparable low levels of the preferred end product
      beta-carotene, as determined by high-performance liquid chromatography. We
      finally succeeded in constructing an S. cerevisiae strain capable of producing
      high levels of beta-carotene, up to 5.9 mg/g (dry weight), which was accomplished
      by the introduction of an additional copy of crtI and tHMG1 into carotenoid
      producing yeast cells. This transformant is promising for further development
      toward the biotechnological production of beta-carotene by S. cerevisiae.

PMID- 17496129
TI  - Identification of the biosynthetic gene cluster and an additional gene for
      resistance to the antituberculosis drug capreomycin.
AB  - Capreomycin (CMN) belongs to the tuberactinomycin family of nonribosomal peptide
      antibiotics that are essential components of the drug arsenal for the treatment
      of multidrug-resistant tuberculosis. Members of this antibiotic family target the
      ribosomes of sensitive bacteria and disrupt the function of both subunits of the
      ribosome. Resistance to these antibiotics in Mycobacterium species arises due to
      mutations in the genes coding for the 16S or 23S rRNA but can also arise due to
      mutations in a gene coding for an rRNA-modifying enzyme, TlyA. While
      Mycobacterium species develop resistance due to alterations in the drug target,
      it has been proposed that the CMN-producing bacterium, Saccharothrix mutabilis
      subsp. capreolus, uses CMN modification as a mechanism for resistance rather than
      ribosome modification. To better understand CMN biosynthesis and resistance in S.
      mutabilis subsp. capreolus, we focused on the identification of the CMN
      biosynthetic gene cluster in this bacterium. Here, we describe the cloning and
      sequence analysis of the CMN biosynthetic gene cluster from S. mutabilis subsp.
      capreolus ATCC 23892. We provide evidence for the heterologous production of CMN
      in the genetically tractable bacterium Streptomyces lividans 1326. Finally, we
      present data supporting the existence of an additional CMN resistance gene.
      Initial work suggests that this resistance gene codes for an rRNA-modifying
      enzyme that results in the formation of CMN-resistant ribosomes that are also
      resistant to the aminoglycoside antibiotic kanamycin. Thus, S. mutabilis subsp.
      capreolus may also use ribosome modification as a mechanism for CMN resistance.

PMID- 17496130
TI  - Glutathione reductase from Lactobacillus sanfranciscensis DSM20451T: contribution
      to oxygen tolerance and thiol exchange reactions in wheat sourdoughs.
AB  - The effect of the glutathione reductase (GshR) activity of Lactobacillus
      sanfranciscensis DSM20451(T) on the thiol levels in fermented sourdoughs was
      determined, and the oxygen tolerance of the strain was also determined. The gshR
      gene coding for a putative GshR was sequenced and inactivated by single-crossover
      integration to yield strain L. sanfranciscensis DSM20451(T)DeltagshR. The gene
      disruption was verified by sequencing the truncated gshR and surrounding regions
      on the chromosome. The gshR activity of L. sanfranciscensis DSM20451(T)DeltagshR
      was strongly reduced compared to that of the wild-type strain, demonstrating that
      gshR indeed encodes an active GshR enzyme. The thiol levels in wheat doughs
      fermented with L. sanfranciscensis DSM20451 increased from 9 microM to 10.5
      microM sulfhydryl/g of dough during a 24-h sourdough fermentation, but in
      sourdoughs fermented with L. sanfranciscensis DSM20451(T)DeltagshR and in
      chemically acidified doughs, the thiol levels decreased to 6.5 to 6.8 microM
      sulfhydryl/g of dough. Remarkably, the GshR-negative strains Lactobacillus pontis
      LTH2587 and Lactobacillus reuteri BR11 exerted effects on thiol levels in dough
      comparable to those of L. sanfranciscensis. In addition to the effect on thiol
      levels in sourdough, the loss of GshR activity in L. sanfranciscensis
      DSM20451(T)DeltagshR resulted in a loss of oxygen tolerance. The gshR mutant
      strain exhibited a strongly decreased aerobic growth rate on modified MRS medium
      compared to either the growth rate under anaerobic conditions or that of the wild
      type strain, and aerobic growth was restored by the addition of cysteine.
      Moreover, the gshR mutant strain was more sensitive to the superoxide-generating
      agent paraquat.

PMID- 17496131
TI  - Effective heat inactivation of Mycobacterium avium subsp. paratuberculosis in raw
      milk contaminated with naturally infected feces.
AB  - The effectiveness of high-temperature, short holding time (HTST) pasteurization
      and homogenization with respect to inactivation of Mycobacterium avium subsp.
      paratuberculosis was evaluated quantitatively. This allowed a detailed
      determination of inactivation kinetics. High concentrations of feces from cows
      with clinical symptoms of Johne's disease were used to contaminate raw milk in
      order to realistically mimic possible incidents most closely. Final M. avium
      subsp. paratuberculosis concentrations varying from 10(2) to 3.5 x 10(5) cells
      per ml raw milk were used. Heat treatments including industrial HTST were
      simulated on a pilot scale with 22 different time-temperature combinations,
      including 60 to 90 degrees C at holding (mean residence) times of 6 to 15 s.
      Following 72 degrees C and a holding time of 6 s, 70 degrees C for 10 and 15 s,
      or under more stringent conditions, no viable M. avium subsp. paratuberculosis
      cells were recovered, resulting in >4.2- to >7.1-fold reductions, depending on
      the original inoculum concentrations. Inactivation kinetic modeling of 69
      quantitative data points yielded an E(a) of 305,635 J/mol and an lnk(0) of 107.2,
      corresponding to a D value of 1.2 s at 72 degrees C and a Z value of 7.7 degrees
      C. Homogenization did not significantly affect the inactivation. The conclusion
      can be drawn that HTST pasteurization conditions equal to 15 s at > or =72
      degrees C result in a more-than-sevenfold reduction of M. avium subsp.
      paratuberculosis.

PMID- 17496132
TI  - Probiotics affect virulence-related gene expression in Escherichia coli O157:H7.
AB  - The attachment of enterohemorrhagic Escherichia coli O157:H7 (EHEC O157) to host
      intestinal epithelial cells is essential for the development of hemorrhagic
      colitis and hemolytic-uremic syndrome in humans. Genes involved in attachment are
      carried within a pathogenicity island named the locus of enterocyte effacement
      (LEE), known to be directly activated by quorum sensing (QS). In the present
      study, we investigated autoinducer-2 (AI-2) production and the expression of
      several virulence-related genes in EHEC O157 grown in the absence and presence of
      a Lactobacillus acidophilus-secreted molecule(s). Transcription of important EHEC
      O157 virulence-related genes was studied by constructing promoter-reporter
      fusions and reverse transcriptase PCR. Shiga toxin (Stx) production was assayed
      by an enzyme immunoassay. When EHEC O157 was grown in the presence of
      chromatographically selected fractions of L. acidophilus La-5 cell-free spent
      medium, we observed a significant reduction of both extracellular AI-2
      concentration and the expression of important virulence-related genes, although
      no significant difference in Stx production was observed. We show here that L.
      acidophilus La-5 secretes a molecule(s) that either acts as a QS signal inhibitor
      or directly interacts with bacterial transcriptional regulators, controlling the
      transcription of EHEC O157 genes involved in colonization.

PMID- 17496133
TI  - Viral abundance, decay, and diversity in the meso- and bathypelagic waters of the
      north atlantic.
AB  - To elucidate the potential importance of deep-water viruses in controlling the
      meso- and bathypelagic picoplankton community, the abundance, decay rate, and
      diversity of the virioplankton community were determined in the meso- and
      bathypelagic water masses of the eastern part of the subtropical North Atlantic.
      Viral abundance averaged 1.4 x 10(6) ml(-1) at around 100 m of depth and
      decreased only by a factor of 2 at 3,000 to 4,000 m of depth. In contrast,
      picoplankton abundance decreased by 1 order of magnitude to the Lower Deep Water
      (LDW; 3,500- to 5,000-m depth). The virus-to-picoplankton ratio increased from 9
      at about 100 m of depth to 110 in the LDW. Mean viral decay rates were 3.5 x 10(
      3) h(-1) between 900 m and 2,750 m and 1.1 x 10(-3) h(-1) at 4,000 m of depth,
      corresponding to viral turnover times of 11 and 39 days, respectively. Pulsed
      field gel electrophoresis fingerprints obtained from the viral community between
      2,400 m and 4,000 m of depth revealed a maximum of only four bands from 4,000 m
      of depth. Based on the high viral abundance and the low picoplankton production
      determined via leucine incorporation, we conclude that the viral production
      calculated from the viral decay is insufficient to maintain the high viral
      abundance in the deep North Atlantic. Rather, we propose that substantial
      allochthonous viral input or lysogenic or pseudolysogenic production is required
      to maintain the high viral abundance detected in the meso- and bathypelagic North
      Atlantic. Consequently, deep-water prokaryotes are apparently far less controlled
      in their abundance and taxon richness by lytic prokaryotic phages than the high
      viral abundance and the virus-to-picoplankton ratio would suggest.

PMID- 17496134
TI  - Development and application of real-time PCR assays for quantification of erm
      genes conferring resistance to macrolides-lincosamides-streptogramin B in
      livestock manure and manure management systems.
AB  - Erythromycin and tylosin are commonly used in animal production, and such use is
      perceived to contribute to the overall antimicrobial resistance (AR) reservoirs.
      Quantitative measurements of this type of AR reservoir in microbial communities
      are required to understand AR ecology (e.g., emergence, persistence, and
      dissemination). We report here the development, validation, and use of six real
      time PCR assays for quantifying six classes of erm genes (classes A through C, F,
      T, and X) that encode the major mechanism of resistance to macrolides
      lincosamides-streptogramin B (MLS(B)). These real-time PCR assays were validated
      and used in quantifying the six erm classes in five types of samples, including
      those from bovine manure, swine manure, compost of swine manure, swine waste
      lagoons, and an Ekokan upflow biofilter system treating hog house effluents. The
      bovine manure samples were found to contain much smaller reservoirs of each of
      the six erm classes than the swine manure samples. Compared to the swine manure
      samples, the composted swine manure samples had substantially reduced erm gene
      abundances (by up to 7.3 logs), whereas the lagoon or the biofilter samples had
      similar erm gene abundances. These preliminary results suggest that the methods
      of manure storage and treatment probably have a substantial impact on the
      persistence and decline of MLS(B) resistance originating from food animals, thus
      likely affecting the dissemination of such resistance genes into the environment.
      The abundances of these erm genes appeared to be positively correlated with those
      of the tet genes determined previously among these samples. These real-time PCR
      assays provide a rapid, quantitative, and cultivation-independent measurement of
      six major classes of erm genes, which should be useful for ecological studies of
      AR.

PMID- 17496135
TI  - Unexpected mechanism of symbiont-induced reversal of insect sex: feminizing
      Wolbachia continuously acts on the butterfly Eurema hecabe during larval
      development.
AB  - When the butterfly Eurema hecabe is infected with two different strains (wHecCI2
      and wHecFem2) of the bacterial endosymbiont Wolbachia, genetic males are
      transformed into functional females, resulting in production of all-female
      broods. In an attempt to understand how and when the Wolbachia endosymbiont
      feminizes genetically male insects, larval insects were fed an antibiotic
      containing diet beginning at different developmental stages until pupation. When
      the adult insects emerged, strikingly, many of them exhibited sexually
      intermediate traits in their wings, reproductive organs, and genitalia. The
      expression of intersexual phenotypes was strong in the insects treated from first
      instar, moderate in the insects treated from third instar, and weak in the
      insects treated from fourth instar. The insects treated from early larval instar
      grew and pupated normally but frequently failed to emerge and died in the pupal
      case. The dead insects in the pupal case contained lower densities of the
      feminizing Wolbachia endosymbiont than the successfully emerged insects, although
      none of them were completely cured of the symbiont infection. These results
      suggest the following: (i) the antibiotic treatment suppressed the population of
      feminizing Wolbachia endosymbionts; (ii) the suppression probably resulted in
      attenuated feminizing activity of the symbiont, leading to expression of
      intersexual host traits; (iii) many of the insects suffered pupal mortality,
      possibly due to either intersexual defects or Wolbachia-mediated addiction; and
      hence (iv) the feminizing Wolbachia endosymbiont continuously acts on the host
      insects during larval development for expression of female phenotypes under a
      male genotype. Our finding may prompt reconsideration of the notion that
      Wolbachia-induced reproductive manipulations are already complete before the
      early embryonic stage and provide insights into the mechanism underlying the
      symbiont-induced reversal of insect sex.

PMID- 17496136
TI  - High abundances of aerobic anoxygenic photosynthetic bacteria in the South
      Pacific Ocean.
AB  - Little is known about the abundance, distribution, and ecology of aerobic
      anoxygenic phototrophic (AAP) bacteria, particularly in oligotrophic
      environments, which represent 60% of the ocean. We investigated the abundance of
      AAP bacteria across the South Pacific Ocean, including the center of the gyre,
      the most oligotrophic water body of the world ocean. AAP bacteria,
      Prochlorococcus, and total prokaryotic abundances, as well as bacteriochlorophyll
      a (BChl a) and divinyl-chlorophyll a concentrations, were measured at several
      depths in the photic zone along a gradient of oligotrophic conditions. The
      abundances of AAP bacteria and Prochlorococcus were high, together accounting for
      up to 58% of the total prokaryotic community. The abundance of AAP bacteria alone
      was up to 1.94 x 10(5) cells ml(-1) and as high as 24% of the overall community.
      These measurements were consistent with the high BChl a concentrations (up to
      3.32 x 10(-3) microg liter(-1)) found at all stations. However, the BChl a
      content per AAP bacterial cell was low, suggesting that AAP bacteria are mostly
      heterotrophic organisms. Interestingly, the biovolume and therefore biomass of
      AAP bacteria was on average twofold higher than that of other prokaryotic cells.
      This study demonstrates that AAP bacteria can be abundant in various oligotrophic
      conditions, including the most oligotrophic regime of the world ocean, and can
      account for a large part of the bacterioplanktonic carbon stock.

PMID- 17496137
TI  - Revealing the prehistoric settlement of Australia by Y chromosome and mtDNA
      analysis.
AB  - Published and new samples of Aboriginal Australians and Melanesians were analyzed
      for mtDNA (n=172) and Y variation (n=522), and the resulting profiles were
      compared with the branches known so far within the global mtDNA and the Y
      chromosome tree. (i) All Australian lineages are confirmed to fall within the
      mitochondrial founder branches M and N and the Y chromosomal founders C and F,
      which are associated with the exodus of modern humans from Africa approximately
      50-70,000 years ago. The analysis reveals no evidence for any archaic maternal or
      paternal lineages in Australians, despite some suggestively robust features in
      the Australian fossil record, thus weakening the argument for continuity with any
      earlier Homo erectus populations in Southeast Asia. (ii) The tree of complete
      mtDNA sequences shows that Aboriginal Australians are most closely related to the
      autochthonous populations of New Guinea/Melanesia, indicating that prehistoric
      Australia and New Guinea were occupied initially by one and the same Palaeolithic
      colonization event approximately 50,000 years ago, in agreement with current
      archaeological evidence. (iii) The deep mtDNA and Y chromosomal branching
      patterns between Australia and most other populations around the Indian Ocean
      point to a considerable isolation after the initial arrival. (iv) We detect only
      minor secondary gene flow into Australia, and this could have taken place before
      the land bridge between Australia and New Guinea was submerged approximately
      8,000 years ago, thus calling into question that certain significant developments
      in later Australian prehistory (the emergence of a backed-blade lithic industry,
      and the linguistic dichotomy) were externally motivated.

PMID- 17496138
TI  - Carotenoid silk coloration is controlled by a carotenoid-binding protein, a
      product of the Yellow blood gene.
AB  - Mechanisms for the uptake and transport of carotenoids, essential nutrients for
      humans, are not well understood in any animal system. The Y (Yellow blood) gene,
      a critical cocoon color determinant in the silkworm Bombyx mori, controls the
      uptake of carotenoids into the intestinal mucosa and the silk gland. Here we
      provide evidence that the Y gene corresponds to the intracellular carotenoid
      binding protein (CBP) gene. In the Y recessive strain, the absence of an exon,
      likely due to an incorrect mRNA splicing caused by a transposon-associated
      genomic deletion, generates a nonfunctional CBP mRNA, resulting in colorless
      hemolymph and white cocoons. Enhancement of carotenoid uptake and coloration of
      the white cocoon was achieved by germ-line transformation with the CBP gene. This
      study demonstrates the existence of a genetically facilitated intracellular
      process beyond passive diffusion for carotenoid uptake in the animal phyla, and
      paves the way for modulating silk color and lipid content through genetic
      engineering.

PMID- 17496139
TI  - High relatedness maintains multicellular cooperation in a social amoeba by
      controlling cheater mutants.
AB  - The control of cheating is important for understanding major transitions in
      evolution, from the simplest genes to the most complex societies. Cooperative
      systems can be ruined if cheaters that lower group productivity are able to
      spread. Kin-selection theory predicts that high genetic relatedness can limit
      cheating, because separation of cheaters and cooperators limits opportunities to
      cheat and promotes selection against low-fitness groups of cheaters. Here, we
      confirm this prediction for the social amoeba Dictyostelium discoideum;
      relatedness in natural wild groups is so high that socially destructive cheaters
      should not spread. We illustrate in the laboratory how high relatedness can
      control a mutant that would destroy cooperation at low relatedness. Finally, we
      demonstrate that, as predicted, mutant cheaters do not normally harm cooperation
      in a natural population. Our findings show how altruism is preserved from the
      disruptive effects of such mutant cheaters and how exceptionally high relatedness
      among cells is important in promoting the cooperation that underlies
      multicellular development.

PMID- 17496140
TI  - A theory of measuring, electing, and ranking.
AB  - The impossibility theorems that abound in the theory of social choice show that
      there can be no satisfactory method for electing and ranking in the context of
      the traditional, 700-year-old model. A more realistic model, whose antecedents
      may be traced to Laplace and Galton, leads to a new theory that avoids all
      impossibilities with a simple and eminently practical method, "the majority
      judgement." It has already been tested.

PMID- 17496141
TI  - Fetal gene therapy of alpha-thalassemia in a mouse model.
AB  - Fetuses with homozygous alpha-thalassemia usually die at the third trimester of
      pregnancy or soon after birth. Hence, the disease could potentially be a target
      for fetal gene therapy. We have previously established a mouse model of alpha
      thalassemia. These mice mimic the human alpha-thalassemic conditions and can be
      used as preclinical models for fetal gene therapy. We tested a lentiviral vector
      containing the HS 2, 3, and 4 of the beta-LCR, a central polypurine tract
      element, and the beta-globin gene promoter directing either the EGFP or the human
      alpha-globin gene. We showed that the GFP expression was erythroid-specific and
      detected in BFU-E colonies and the erythroid progenies of CFU-GEMM. For in utero
      gene delivery, we did yolk sac vessel injection at midgestation of mouse embryos.
      The recipient mice were analyzed after birth for human alpha-globin gene
      expression. In the newborn, human alpha-globin gene expression was detected in
      the liver, spleen, and peripheral blood. The human alpha-globin gene expression
      was at the peak at 3-4 months, when it reached 20% in some recipients. However,
      the expression declined at 7 months. Colony-forming assays in these mice showed
      low abundance of the transduced human alpha-globin gene in their BFU-E and CFU
      GEMM and the lack of its transcript. Thus, lentiviral vectors can be an effective
      vehicle for delivering the human alpha-globin gene into erythroid cells in utero,
      but, in the mouse model, delivery at late midgestation could not transduce
      hematopoietic stem cells adequately to sustain gene expression.

PMID- 17496142
TI  - Deletion of PrBP/delta impedes transport of GRK1 and PDE6 catalytic subunits to
      photoreceptor outer segments.
AB  - The mouse Pde6d gene encodes a ubiquitous prenyl binding protein, termed
      PrBP/delta, of largely unknown physiological function. PrBP/delta was originally
      identified as a putative rod cGMP phosphodiesterase (PDE6) subunit in the retina,
      where it is relatively abundant. To investigate the consequences of Pde6d
      deletion in retina, we generated a Pde6d(-/-) mouse by targeted recombination.
      Although manifesting reduced body weight, the Pde6d(-/-) mouse was viable and
      fertile and its retina developed normally. Immunocytochemistry showed that
      farnesylated rhodopsin kinase (GRK1) and prenylated rod PDE6 catalytic subunits
      partially mislocalized in Pde6d(-/-) rods, whereas rhodopsin was unaffected. In
      Pde6d(-/-) rod single-cell recordings, sensitivity to single photons was
      increased and saturating flash responses were prolonged. Pde6d(-/-) scotopic
      paired-flash electroretinograms indicated a delay in recovery of the dark state,
      likely due to reduced levels of GRK1 in rod outer segments. In Pde6d(-/-) cone
      outer segments, GRK1 and cone PDE6alpha' were present at very low levels and the
      photopic b-wave amplitudes were reduced by 70%. Thus the absence of PrBP/delta in
      retina impairs transport of prenylated proteins, particularly GRK1 and cone PDE,
      to rod and cone outer segments, resulting in altered photoreceptor physiology and
      a phenotype of a slowly progressing rod/cone dystrophy.

PMID- 17496143
TI  - Coupling between allosteric transitions in GroEL and assisted folding of a
      substrate protein.
AB  - Escherichia coli chaperonin, GroEL, helps proteins fold under nonpermissive
      conditions. During the reaction cycle, GroEL undergoes allosteric transitions in
      response to binding of a substrate protein (SP), ATP, and the cochaperonin GroES.
      Using coarse-grained representations of the GroEL and GroES structures, we
      explore the link between allosteric transitions and the folding of a model SP, a
      de novo-designed four-helix bundle protein, with low spontaneous yield. The
      ensemble of GroEL-bound SP is less structured than the bulk misfolded structures.
      Upon binding, which kinetically occurs in two stages, the SP loses not only
      native tertiary contacts but also experiences a decrease in helical content.
      During multivalent binding and the subsequent ATP-driven transition of GroEL the
      SP undergoes force-induced stretching. Upon encapsulation, which occurs upon
      GroES binding, the SP finds itself in a "hydrophilic" cavity in which it can
      reach the folded conformation. Surprisingly, we find that the yield of the native
      state in the expanded GroEL cavity is relatively small even after it remains in
      it for twice the spontaneous folding time. Thus, in accord with the iterative
      annealing mechanism, multiple rounds of binding, partial unfolding, and release
      of the SP are required to enhance the yield of the folded SP.

PMID- 17496144
TI  - Restructuring of the dinucleotide-binding fold in an NADP(H) sensor protein.
AB  - NAD(P) has long been known as an essential energy-carrying molecule in cells.
      Recent data, however, indicate that NAD(P) also plays critical signaling roles in
      regulating cellular functions. The crystal structure of a human protein, HSCARG,
      with functions previously unknown, has been determined to 2.4-A resolution. The
      structure reveals that HSCARG can form an asymmetrical dimer with one subunit
      occupied by one NADP molecule and the other empty. Restructuring of its NAD(P)
      binding Rossmann fold upon NADP binding changes an extended loop to an alpha
      helix to restore the integrity of the Rossmann fold. The previously unobserved
      restructuring suggests that HSCARG may assume a resting state when the level of
      NADP(H) is normal within the cell. When the NADP(H) level passes a threshold, an
      extensive restructuring of HSCARG would result in the activation of its
      regulatory functions. Immunofluorescent imaging shows that HSCARG redistributes
      from being associated with intermediate filaments in the resting state to being
      dispersed in the nucleus and the cytoplasm. The structural change of HSCARG upon
      NADP(H) binding could be a new regulatory mechanism that responds only to a
      significant change of NADP(H) levels. One of the functions regulated by HSCARG
      may be argininosuccinate synthetase that is involved in NO synthesis.

PMID- 17496145
TI  - Dissecting the multistep reaction pathway of an RNA enzyme by single-molecule
      kinetic "fingerprinting".
AB  - Single-molecule FRET is a powerful tool for probing the kinetic mechanism of a
      complex enzymatic reaction. However, not every reaction intermediate can be
      identified via a distinct FRET value, making it difficult to fully dissect a
      multistep reaction pathway. Here, we demonstrate a method using sequential
      kinetic experiments to differentiate each reaction intermediate by a distinct
      time sequence of FRET signal (a kinetic "fingerprint"). Our model system, the two
      way junction hairpin ribozyme, catalyzes a multistep reversible RNA cleavage
      reaction, which comprises two structural transition steps (docking/undocking) and
      one chemical reaction step (cleavage/ligation). Whereas the docked and undocked
      forms of the enzyme display distinct FRET values, the cleaved and ligated forms
      do not. To overcome this difficulty, we used Mg(2+) pulse-chase experiments to
      differentiate each reaction intermediate by a distinct kinetic fingerprint at the
      single-molecule level. This method allowed us to unambiguously determine the rate
      constant of each reaction step and fully characterize the reaction pathway by
      using the chemically competent enzyme-substrate complex. We found that the
      ligated form of the enzyme highly favors the docked state, whereas undocking
      becomes accelerated upon cleavage by two orders of magnitude, a result different
      from that obtained with chemically blocked substrate and product analogs. The
      overall cleavage reaction is rate-limited by the docking/undocking kinetics and
      the internal cleavage/ligation equilibrium, contrasting the rate-limiting
      mechanism of the four-way junction ribozyme. These results underscore the kinetic
      interdependence of reversible steps on an enzymatic reaction pathway and
      demonstrate a potentially general route to dissect them.

PMID- 17496146
TI  - Parietal stimulation destabilizes spatial updating across saccadic eye movements.
AB  - Saccadic eye movements cause sudden and global shifts in the retinal image.
      Rather than causing confusion, however, eye movements expand our sense of space
      and detail. In macaques, a stable representation of space is embodied by neural
      populations in intraparietal cortex that redistribute activity with each saccade
      to compensate for eye displacement, but little is known about equivalent updating
      mechanisms in humans. We combined noninvasive cortical stimulation with a double
      step saccade task to examine the contribution of two human intraparietal areas to
      transsaccadic spatial updating. Right hemisphere stimulation over the posterior
      termination of the intraparietal sulcus (IPSp) broadened and shifted the
      distribution of second-saccade endpoints, but only when the first-saccade was
      directed into the contralateral hemifield. By interleaving trials with and
      without cortical stimulation, we show that the shift in endpoints was caused by
      an enduring effect of stimulation on neural functioning (e.g., modulation of
      neuronal gain). By varying the onset time of stimulation, we show that the
      representation of space in IPSp is updated immediately after the first-saccade.
      In contrast, stimulation of an adjacent IPS site had no such effects on second
      saccades. These experiments suggest that stimulation of IPSp distorts an eye
      position or displacement signal that updates the representation of space at the
      completion of a saccade. Such sensory-motor integration in IPSp is crucial for
      the ongoing control of action, and may contribute to visual stability across
      saccades.

PMID- 17496147
TI  - Principal-components analysis of shape fluctuations of single DNA molecules.
AB  - Thermal fluctuations agitate molecules in solution over a broad range of times
      and distances. By passively watching the shape fluctuations of a thermally driven
      biomolecule, one can infer properties of the underlying interactions that
      determine the motion. We applied this concept to single molecules of
      fluorescently labeled lambda-DNA, a key model system for polymer physics. In
      contrast to most other single-molecule DNA experiments, we examined the
      unstretched, equilibrium state of DNA by using an anti-Brownian electrokinetic
      trap to confine the center of mass of the DNA without perturbing its internal
      dynamics. We analyze the long-wavelength conformational normal modes, calculate
      their spring constants, and measure linear and nonlinear couplings between modes.
      The modes show strong signs of nonlinear hydrodynamics, a feature of the
      underlying equations of polymer dynamics that has not previously been reported
      and is neglected in the widely used Rouse and Zimm approximations.

PMID- 17496148
TI  - Crystal structure of RseB and a model of its binding mode to RseA.
AB  - The bacterial envelope stress response senses stress signals in the
      extracytoplasmic compartment, and activates sigma(E)-dependent transcription by
      degrading its antisigma factor RseA. RseB, a binding partner of RseA, plays a
      pivotal role in regulating this response, but its molecular mechanism is not
      understood. We therefore determined the crystal structure of Escherichia coli
      RseB at a resolution of 2.4 A. RseB is composed of two domains linked by a
      flexible linker and forms a loosely packed dimer with two grooves on each side.
      This structural feature is confirmed by small-angle scattering in solution.
      Analysis of the binding of various RseA mutants to RseB allowed us to identify
      the major RseB-binding motif in RseA. These data, coupled with analysis of small
      angle scattering of the RseA/RseB complex in solution, leads us to propose that
      two RseAs bind to the grooves of the dimeric RseB by conserved residues. The
      implications for modulating proteolytic cleavage of RseA are discussed.

PMID- 17496149
TI  - Selective adapter recruitment and differential signaling networks by VEGF vs.
      shear stress.
AB  - Vascular endothelial cells are continuously exposed to mechanical and chemical
      stimuli, such as shear stress and VEGF, respectively. It is still not clear how
      cells perceive these stimuli and orchestrate their responses. Studying the
      molecular mechanism by which shear stress and VEGF regulate the signaling
      pathways in bovine endothelial aortic cells, we found that VEGF induced a rapid
      association of VEGF receptor 2 (Flk-1) with Nck beta, but shear stress did not
      have such an effect. SU1498 (a specific inhibitor of Flk-1) and Nck beta(nm) (a
      negative mutant of Nck beta) blocked the VEGF-induced ERK and JNK activities.
      Only SU1498, but not Nck beta(nm), inhibited the shear-induced ERK activity.
      Furthermore, neither SU1498 nor Nck beta(nm) had significant effects on the shear
      induced JNK activity, which can be blocked by inhibitors of Src family kinase and
      ROCK kinase. Therefore, mechanical (shear stress) and chemical (VEGF) stimuli
      diverge at the receptor Flk-1 in terms of the recruitment of the adapter protein
      Nck beta, and they employ different components of the complex signaling network
      in regulating downstream molecules, e.g., ERK and JNK.

PMID- 17496150
TI  - Studies on peptide:N-glycanase-p97 interaction suggest that p97 phosphorylation
      modulates endoplasmic reticulum-associated degradation.
AB  - During endoplasmic reticulum-associated degradation, the multifunctional AAA
      ATPase p97 is part of a protein degradation complex. p97 associates via its N
      terminal domain with various cofactors to recruit ubiquitinated substrates. It
      also interacts with alternative substrate-processing cofactors, such as Ufd2,
      Ufd3, and peptide:N-glycanase (PNGase) in higher eukaryotes. These cofactors
      determine different fates of the substrates and they all bind outside of the N
      terminal domain of p97. Here, we describe a cofactor-binding motif of p97
      contained within the last 10 amino acid residues of the C terminus, which is both
      necessary and sufficient to mediate interactions of p97 with PNGase and Ufd3. The
      crystal structure of the N-terminal domain of PNGase in complex with this motif
      provides detailed insight into the interaction between p97 and its substrate
      processing cofactors. Phosphorylation of p97's highly conserved penultimate
      tyrosine residue, which is the main phosphorylation site during T cell receptor
      stimulation, completely blocks binding of either PNGase or Ufd3 to p97. This
      observation suggests that phosphorylation of this residue modulates endoplasmic
      reticulum-associated protein degradation activity by discharging substrate
      processing cofactors.

PMID- 17496151
TI  - Cyclooxygenase-2 deficiency exacerbates bleomycin-induced lung dysfunction but
      not fibrosis.
AB  - Cyclooxygenase (COX)-derived eicosanoids have been implicated in the pathogenesis
      of pulmonary fibrosis. Uncertainty regarding the influence of COX-2 on
      experimental pulmonary fibrosis prompted us to clarify the fibrotic and
      functional effects of intratracheal bleomycin administration in mice genetically
      deficient in COX-2. Further, the effects of airway-specific COX-1 overexpression
      on fibrotic and functional outcomes in wild-type and COX-2 knockout mice were
      assessed. Equivalent increases in airway cell influx, lung collagen content, and
      histopathologic evidence of fibrosis were observed in wild-type and COX-2
      knockout mice 21 d after bleomycin treatment, suggesting that COX-2 deficiency
      did not alter the extent or severity of fibrosis in this model. However,
      bleomycin-induced alterations in respiratory mechanics were more severe in COX-2
      knockout mice than in wild-type mice, as illustrated by a greater decrease in
      static compliance compared with genotype-matched, saline-treated control mice (26
      +/- 3% versus 11 +/- 4% decreases for COX-2 knockout and wild-type mice,
      respectively; P < 0.05). The influence of COX-1 overexpression in airway Clara
      cells was also examined. Whereas the fibrotic effects of bleomycin were not
      altered in wild-type or COX-2 knockout mice overexpressing COX-1, the exaggerated
      lung function decrement in bleomycin-treated COX-2 knockout mice was prevented by
      COX-1 overexpression and coincided with decreased airway cysteinyl leukotriene
      levels. Collectively, these data suggest an important regulatory role for COX-2
      in the maintenance of lung function in the setting of lung fibrosis, but not in
      the progression of the fibrotic process per se.

PMID- 17496153
TI  - Identification of a mouse ghrelin gene transcript that contains intron 2 and is
      regulated in the pituitary and hypothalamus in response to metabolic stress.
AB  - The mouse ghrelin gene contains 5 exons (Ex), with Ex2-Ex5 encoding a 117 amino
      acid preproprotein that is processed to yield a 28 amino acid mature peptide. The
      current study examined if pituitary (PIT) and hypothalamus (HPT) ghrelin
      expression is up-regulated in response to fasting and down-regulated in obesity,
      as previously reported in the stomach. In the process of establishing a
      quantitative real-time RT-PCR system to accurately assess the changes in PIT and
      HPT ghrelin mRNA levels, we observed that primer sets located in Ex2 and Ex3
      amplified a ghrelin transcript that contained the entire intron 2 (In2). Size and
      sequence analysis of RT-PCR products using multiple primer sets located
      throughout the ghrelin gene suggested that the In2-ghrelin variant contains Ex2
      and Ex3, but lacks Ex1, Ex4, and Ex5. In2-ghrelin variant mRNA was not detected
      in stomach extracts, while expression levels were 10- and 50-fold greater than
      that of the native ghrelin transcript in the PIT and HPT respectively. In2
      ghrelin variant mRNA levels increased in the PIT after 24 h fasting and decreased
      in the HPT and PIT of diet-induced obese mice. These changes may be due to the
      changes in circulating insulin or IGF-I, since both decreased In2-ghrelin variant
      expression in a mouse HPT cell line (N6) and in primary mouse PIT cell cultures.
      The fact that In2-ghrelin variant mRNA levels are dependent on energy intake in
      the PIT and HPT suggests that this transcript may encode a peptide important in
      coordinating the neuroendocrine response to metabolic stress.

PMID- 17496152
TI  - Genomic profile of matrix and vasculature remodeling in TGF-alpha induced
      pulmonary fibrosis.
AB  - Expression of transforming growth factor alpha (TGF-alpha) in the respiratory
      epithelium of transgenic mice caused pulmonary fibrosis, cachexia, pulmonary
      hypertension, and altered lung function. To identify genes and molecular pathways
      mediating lung remodeling, mRNA microarray analysis was performed at multiple
      times after TGF-alpha expression and revealed changes consistent with a role for
      TGF-alpha in the regulation of extracellular matrix and vasculogenesis.
      Transcripts for extracellular matrix proteins were augmented along with
      transcripts for genes previously identified to have roles in pulmonary fibrosis,
      including tenascin C, osteopontin, and serine (or cysteine) peptidase inhibitor,
      clade F, member 1. Transcripts regulating vascular processes including endothelin
      receptor type B, endothelial-specific receptor tyrosine kinase, and caveolin,
      caveolae protein 1 were decreased. When TGF-alpha expression was no longer
      induced, lung remodeling partially reversed and lung function and pulmonary
      hypertension normalized. Transcripts increased during resolution included
      midkine, matrix metalloproteinase 2, and hemolytic complement. Hierarchical
      clustering revealed that genes regulated by TGF-alpha were similar to those
      altered in the lungs of patients with idiopathic pulmonary fibrosis. These
      studies support a role for epithelial cell-derived TGF-alpha in the regulation of
      processes that alter the airway and vascular architecture and function.

PMID- 17496154
TI  - Expression of thyroid hormone receptors A and B in developing rat tissues;
      evidence for extensive posttranscriptional regulation.
AB  - The perinatal changes in the pattern of expression of the thyroid hormone
      receptor (TR) isoforms TRalpha (1) TRalpha (2), TRbeta (1), and TRbeta (2) were
      investigated using in situ hybridization and immunohistochemistry, and RT-PCR and
      western blotting as visualization and quantification techniques respectively. In
      liver, lung, and kidney, TRalpha mRNA was expressed in the stromal and TRbeta
      mRNA in the parenchymal component of the tissues. When compared with liver,
      TRalpha mRNA concentrations were tenfold higher in lung, kidney, and intestine,
      and 100-fold higher in brain, with TRalpha (2) mRNA concentrations exceeding
      those of TRalpha (1) 5-to 10-fold. Tissue TRbeta (1) mRNA concentrations were
      similar in liver, lung, and brain, and 3- to 5-fold higher in kidney and
      intestine. None of the TRbeta (2) mRNA could be detected outside the pituitary.
      Tissue TRalpha (2) and TRbeta (1) protein levels reached adult levels at 5 days
      before birth, whereas TRalpha (1) protein peaked after birth. Because of the
      distinct time-course of thyroid hormone-binding receptors TRalpha (1) and TRbeta
      (1), we speculate that an initiating, TRbeta (1)-mediated signaling from the
      parenchyma is followed by a TRalpha (1)-mediated response in the stroma. When
      compared with organs with a complementary parenchymal-stromal expression pattern,
      organs with extensive cellular co-expression of TRalpha and TRbeta (brain and
      intestinal epithelium) were characterized by a very low TRalpha protein: mRNA
      ratio, implying a low translational efficiency of TR mRNA or a high turnover of
      TR protein. The data indicate that the TR-dependent regulatory cascades are
      controlled differently in organs with a complementary tissue expression pattern
      and in those with cellular co-expression of the TRalpha and TRbeta genes.

PMID- 17496155
TI  - Sp1-mediated transcription is involved in the induction of leptin by insulin
      stimulated glucose metabolism.
AB  - We have previously demonstrated that insulin-stimulated glucose metabolism, and
      not insulin per se, mediates the effects of insulin to increase the
      transcriptional activity of the leptin promoter in adipocytes. Here, we sought to
      identify the specific cis-acting DNA elements required for the upregulation of
      leptin gene transcription in response to insulin-mediated glucose metabolism. To
      accomplish this, 3T3-L1 cells and primary rat adipocytes were transfected with a
      series of luciferase reporter genes containing portions of the mouse leptin
      promoter. Using this method, we identified an element between -135 and -95 bp
      (relative to the transcriptional start site) that mediated transcription in
      response to insulin-stimulated glucose metabolism in adipocytes. This effect was
      abolished by incubation with 2-deoxy-d-glucose, a competitive inhibitor of
      glucose metabolism. Gel shift electrophoretic mobility shift assays confirmed
      that the stimulatory effect of insulin-mediated glucose metabolism on leptin
      transcription was mediated by a previously identified Sp1 site. Consistent with
      these findings, incubation of primary rat adipocytes with WP631, a specific
      inhibitor of specificity protein (Sp)1-dependent transcription, inhibited glucose
      and insulin-stimulated, but not basal, leptin secretion. Together, these
      findings support a key role for Sp1 in the transcriptional activation of the
      leptin gene promoter by insulin-mediated glucose metabolism.

PMID- 17496156
TI  - Coexpression of Wilms' tumor suppressor 1 (WT1) and androgen receptor (AR) in the
      genital tract of human male embryos and regulation of AR promoter activity by
      WT1.
AB  - The Wilms' tumor suppressor 1 (WT1) is one of the key regulators of early male
      genital development. The androgen receptor (AR) is the major local factor
      responsible for the development of the male genitalia. As a subset of patients,
      with WT1 mutations and virilization defects, were found to present normal
      testosterone producing testes after birth, which suggests androgen resistance, we
      hypothesized that WT1 and AR might functionally interact during the development
      of the external genitalia. Coexpression of WT1 and AR was found in the mesenchyme
      surrounding the urogenital sinus, the mesonephros, and the Mullerian duct at 7
      weeks p.c. and in the epididimys, vas deferens, and the gubernaculum testes from
      13 to 27 weeks p.c. in human male embryos. A modification of AR expression by WT1
      (WT1+/+, WT1+/-, and WT1+/- R394W) was seen in CV1, Hela, LNCaP, and T293 cells.
      WT1 was shown to increase or decrease AR expression depending on the cell line
      (1.6- to 3.7-fold). In this study, we consider LNCaP and T293 cells as the most
      physiological cell system, as both originate from the human urogenital tract. In
      these cell lines, a repressional effect of the mutant WT1+/- R394W (0.5-fold) on
      AR expression in comparison to the wild-type WT1+/- could be demonstrated. From
      our data, we conclude that a functional interaction of WT1 and AR might play a
      role during the development of the male external genitalia, but as the regulatory
      effects were moderate most likely in concert with other local cofactors.

PMID- 17496157
TI  - Two differentially active alternative promoters control the expression of the
      zebrafish orphan nuclear receptor gene Rev-erbalpha.
AB  - The orphan nuclear receptor Rev-erbalpha (NR1D1) plays an important role in the
      regulation of the circadian pacemaker and its expression has been shown to be
      regulated with a robust circadian rhythm in zebrafish and mammals. In addition,
      in zebrafish its expression has been shown to be developmentally regulated. In
      order to analyze the mechanisms of the zfRev-erbalpha gene regulation, we have
      isolated its 5'-upstream region. We found that two promoters control the zfRev
      erbalpha expression. The first one (ZfP1) is characterized by a very high degree
      of sequence identity with the mammalian P1 promoter and contains, as the
      mammalian P1, a functional Rev-erbalpha-binding site (RevDR2). Inhibition of
      zfRev-erbalpha activity in zebrafish embryos using antisense-morpholino knockdown
      results in an increase of zfRev-erbalpha gene expression suggesting that zfRev
      erbalpha is repressing its own transcription in vivo. In addition, we show that
      ROR orphan receptors also regulate in vitro and in vivo zfRev-erbalpha gene
      expression through the same RevDR2 element. In contrast, the second promoter ZfP2
      is strikingly different from the mammalian P2: its sequence is not conserved
      between zebrafish and mammals and is not regulated by the same transcription
      factors. Together, these data suggest that ZfP1 is orthologous to the mammalian
      P1 promoter, whereas zebrafish ZfP2 has no mammalian ortholog and does not
      function like ZfP1 to control Rev-erbalpha expression.

PMID- 17496158
TI  - Non-monotonic dose-response relationship in steroid hormone receptor-mediated
      gene expression.
AB  - Steroid hormone receptors are the targets of many environmental endocrine active
      chemicals (EACs) and synthetic drugs used in hormone therapy. While most of these
      chemical compounds have a unidirectional and monotonic effect, certain EACs can
      display non-monotonic dose-response behaviors and some synthetic drugs are
      selective endocrine modulators. Mechanisms underlying these complex endocrine
      behaviors have not been fully understood. By formulating an ordinary differential
      equation-based computational model, we investigated in this study the steady
      state dose-response behavior of exogenous steroid ligands in an endogenous
      hormonal background under various parameter conditions. Our simulation revealed
      that non-monotonic dose-responses in gene expression can arise within the
      classical genomic framework of steroid signaling. Specifically, when the
      exogenous ligand is an agonist, a U-shaped dose-response appears as a result of
      the inherently nonlinear process of receptor homodimerization. This U-shaped dose
      response curve can be further modulated by mixed-ligand heterodimers formed
      between endogenous ligand-bound and exogenous ligand-bound receptor monomers.
      When the heterodimer is transcriptionally inactive or repressive, the magnitude
      of U-shape increases; conversely, when the heterodimer is transcriptionally
      active, the magnitude of U-shape decreases. Additionally, we found that an
      inverted U-shaped dose-response can arise when the heterodimer is a strong
      transcription activator regardless of whether the exogenous ligand is an agonist
      or antagonist. Our work provides a novel mechanism for non-monotonic,
      particularly U-shaped, dose-response behaviors observed with certain steroid
      mimics, and may help not only understand how selective steroid receptor
      modulators work but also improve risk assessment for EACs.

PMID- 17496159
TI  - Resolvin E1 promotes mucosal surface clearance of neutrophils: a new paradigm for
      inflammatory resolution.
AB  - Migration of neutrophils (PMN) across epithelia is a pathological hallmark of
      numerous mucosal diseases. Whereas lesions at mucosal surfaces are generally self
      limiting, endogenous mechanisms of resolution are incompletely understood.
      Previous studies revealed that resolvins directly act on PMN to attenuate
      transendothelial migration, less is known about the influence of resolvins on PMN
      epithelial interactions and whether they act on epithelia. We studied the
      dynamics of resolvin E1 (RvE1) actions on leukocyte transepithelial migration.
      PMN exposure to RvE1 or chemerin (peptide agonist of ChemR23) reduced
      transepithelial migration in a concentration-dependent manner. Conversely,
      activation of epithelial ChemR23 promoted apical clearance of PMN. A nonbiased
      screen of known PMN ligands expressed on epithelial cells in response to RvE1
      revealed selective induction of CD55, an apically expressed antiadhesive
      molecule. CD55 promoter analysis demonstrated that both RvE1 and chemerin
      activate the CD55 promoter. Inhibition of CD55 by neutralizing antibody prevented
      RvE1-dependent augmentation of apical PMN clearance. Taken together these
      findings implicate a "two-hit" model of inflammatory resolution, whereby
      activation of the PMN RvE1 receptor attenuates transepithelial migration and
      subsequent actions on the epithelium promote CD55-dependent clearance of PMN
      across the epithelial cell surface promoting active inflammatory resolution.

PMID- 17496160
TI  - Messenger RNA oxidation is an early event preceding cell death and causes reduced
      protein expression.
AB  - We previously reported that up to 50% of messenger RNAs (mRNA) are oxidatively
      damaged in the affected area of Alzheimer's disease (AD) brains. The role of RNA
      oxidation in the cell death process is unknown. In the present study, we used
      cortical primary dissociated cultures to investigate the relationship between RNA
      oxidation and neuron degeneration induced by various insults, including hydrogen
      peroxide, glutamate, and amyloid beta peptide. These insults mediate the
      production of reactive oxygen species and thus induce oxidative stress. The
      results showed that RNA oxidation was an early event far preceding cell death,
      not merely a consequence of dying cells. RNA oxidation occurred primarily in a
      distinct group of neurons that died later. Identification of oxidized RNA species
      revealed that significant amounts of mRNAs were oxidized and that some mRNA
      species were more susceptible to oxidative damage, consistent with findings in
      the AD brain. The level of protein corresponding to the oxidized mRNA species was
      significantly decreased. Polyribosome analysis indicated that oxidized bases in
      mRNAs caused ribosome stalling on the transcripts, which led to a decrease of
      protein expression. These results suggest that RNA oxidation may be directly
      associated with neuronal deterioration, rather than harmless epiphenomena, during
      the process of neurodegeneration.

PMID- 17496161
TI  - Post-translational modification of POU domain transcription factor Oct-4 by SUMO
      1.
AB  - POU domain transcription factor Oct-4 plays a crucial role in maintaining self
      renewal and pluripotency of embryonic stem (ES) cells in a concentration
      dependent manner. However, the molecular mechanism controlling Oct-4 levels in ES
      cells remains largely unknown. To explore the molecular mechanism regulating Oct
      4 function, we constructed a mouse ES cell cDNA library and performed yeast two
      hybrid screening using the POU domain of Oct-4 as bait. Here, we present novel
      evidence for Oct-4 interaction with Ubc9, an E2 conjugation enzyme for SUMO
      modification, and its modification by SUMO-1. The SUMO acceptor site was
      identified at lysine residue 118. Importantly, disruption of Oct-4 sumoylation
      reduced Oct-4 protein stability and self-renewal capacity in ES cells.
      Interestingly, expression of cYes was found to reduce when Oct-4 sumoylation was
      disrupted or Oct-4 expression downregulated in ES cells. We further demonstrate
      that Oct-4 was recruited to the cYes promoter region, suggesting that cYes might
      be a novel downstream gene of Oct-4. Taken together, we first demonstrate the
      post-translational modification of endogenous Oct-4 by SUMO and the role of
      sumoylation in regulating Oct-4 protein stability and function. Our findings
      provide new evidence for the important role of post-translational modification in
      controlling Oct-4 function in ES cells.

PMID- 17496162
TI  - SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac
      myocytes after myocardial infarction.
AB  - Stem cell transplantation at the time of acute myocardial infarction (AMI)
      improves cardiac function. Whether the improved cardiac function results from
      regeneration of cardiac myocytes, modulation of remodeling, or preservation of
      injured tissue through paracrine mechanisms is actively debated. Because no
      specific stem cell population has been shown to be optimal, we investigated
      whether the benefit of stem cell transplantation could be attributed to a trophic
      effect on injured myocardium. Mesenchymal stem cells secrete SDF-1 and the
      interaction of SDF-1 with its receptor, CXCR4, increases survival of progenitor
      cells. Therefore, we compared the effects of MSC and MSC engineered to
      overexpress SDF-1 on cardiac function after AMI. Tail vein infusion of syngeneic
      MSC and MSC:SDF-1 1 day after AMI in the Lewis rat led to improved cardiac
      function by echocardiography by 70.7% and 238.8%, respectively, compared with
      saline controls 5 wk later. The beneficial effects of MSC and MSC:SDF-1
      transplantation were mediated primarily through preservation, not regeneration of
      cardiac myocytes within the infarct zone. The direct effect of SDF-1 on cardiac
      myocytes was due to the observation that, between 24 and 48 h after AMI, SDF-1
      expressing MSC increased cardiac myocyte survival, vascular density (18.2+/-4.0
      vs. 7.6+/-2.3 vessels/mm2, P<0.01; SDF-1:MSC vs. MSC), and cardiac myosin
      positive area (MSC: 49.5%; mSC:SDF-1: 162.1%) within the infarct zone. There was
      no evidence of cardiac regeneration by the infused MSC or endogenous cardiac stem
      cells based on lack of evidence for cardiac myocytes being derived from
      replicating cells. These results indicate that stem cell transplantation may have
      significant beneficial effects on injured organ function independent of tissue
      regeneration and identify SDF-1:CXCR4 binding as a novel target for myocardial
      preservation.

PMID- 17496163
TI  - Human hydroxysteroid sulfotransferase SULT2B1 pharmacogenomics: gene sequence
      variation and functional genomics.
AB  - The human hydroxysteroid sulfotransferase (SULT) 2B1 gene is a member of the
      cytosolic SULT gene superfamily. The two SULT2B1 isoforms, SULT2B1a and SULT2B1b,
      are encoded by a single gene as a result of alternative transcription initiation
      and alternative splicing. SULT2B1b catalyzes the sulfonation of 3beta
      hydroxysteroid hormones and cholesterol, whereas SULT2B1a preferentially
      catalyzes pregnenolone sulfonation. We used a genotype-to-phenotype approach to
      identify and characterize common sequence variation in SULT2B1. Specifically, we
      resequenced all exons, splice junctions, and approximately 2.5 kb of the 5'
      flanking regions (FRs) for each isoform using 60 DNA samples each from African
      American and Caucasian-American subjects. We observed 100 polymorphisms,
      including four nonsynonymous coding single nucleotide polymorphisms and one 6
      base pair deletion-all within the "shared" region of the open reading frame.
      Functional genomic studies of the wild type (WT) and five variant allozymes for
      each isoform performed with a mammalian expression system showed that variant
      allozyme activities ranged from 64 to 88% of WT for SULT2B1a and from 76 to 98%
      for SULT2B1b. Relative levels of immunoreactive protein were similar to those for
      enzyme activity. Luciferase reporter gene constructs for 2.5 kb of the SULT2B1b
      5'-FR displayed a cell line-dependent pattern of variation in activity. Finally,
      deletion of the proline-rich SULT2B1 carboxyl terminus resulted in intracellular
      protein aggregate formation and accelerated degradation of the truncated protein.
      These studies resulted in the identification of common SULT2B1 gene sequence
      variation, as well as insight into the effects of that variation on the function
      of this important steroid-metabolizing enzyme.

PMID- 17496164
TI  - Memantine inhibits ATP-dependent K+ conductances in dopamine neurons of the rat
      substantia nigra pars compacta.
AB  - 1-Amino-3,5-dimethyl-adamantane (memantine) is a noncompetitive N-methyl-D
      aspartate (NMDA) receptor antagonist used in clinical practice to treat
      neurodegenerative disorders that could be associated with excitotoxic cell death.
      Because memantine reduces the loss of dopamine neurons of the substantia nigra
      pars compacta (SNc) in animal models of Parkinson's disease, we examined the
      effects of this drug on dopamine cells of the SNc. Besides inhibition of NMDA
      receptor-mediated currents, memantine (30 and 100 microM) increased the
      spontaneous firing rate of whole-cell recorded dopamine neurons in a midbrain
      slice preparation. Occasionally, a bursting activity was observed. These effects
      were independent from the block of NMDA receptors and were prevented in neurons
      dialyzed with a high concentration of ATP (10 mM). An increase in firing rate was
      also induced by the ATP-sensitive potassium (K(ATP)) channel antagonist
      tolbutamide (300 microM), and this increase occluded further effects of
      memantine. In addition, K(ATP) channel-mediated outward currents, induced by
      hypoxia, were inhibited by memantine (30 and 100 microM) in the presence of the
      NMDA receptor antagonist (5S, 10R)-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) (10 microM). An increase in
      the spontaneous firing rate by memantine was observed in dopamine neurons
      recorded with extracellular planar 8 x 8 multielectrodes in conditions of
      hypoglycemia. These results highlight K(ATP) channels as possible relevant
      targets of memantine effects in the brain. Moreover, in view of a proposed role
      of K(ATP) conductances in dopamine neuron degeneration, they suggest another
      mechanism of action underlying the protective role of memantine in Parkinson's
      disease.

PMID- 17496165
TI  - A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits
      neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal
      models of pulmonary inflammation.
AB  - Sch527123 [2-hydroxy-N,N-dimethyl-3-[[2-[[1(R)-(5-methyl-2-furanyl)propyl]amino]
      3,4-dioxo-1-cyclobuten-1-yl]amino]ben-zamide] is a potent, selective antagonist
      of the human CXCR1 and CXCR2 receptors (Gonsiorek et al., 2007). Here we describe
      its pharmacologic properties at rodent CXCR2 and at the CXCR1 and CXCR2 receptors
      in the cynomolgus monkey, as well as its in vivo activity in models demonstrating
      prominent pulmonary neutrophilia, goblet cell hyperplasia, and mucus production.
      Sch527123 bound with high affinity to the CXCR2 receptors of mouse (K(d) = 0.20
      nM), rat (K(d) = 0.20 nM), and cynomolgus monkey (K(d) = 0.08 nM) and was a
      potent antagonist of CXCR2-mediated chemotaxis (IC(50) approximately 3-6 nM). In
      contrast, Sch527123 bound to cynomolgus CXCR1 with lesser affinity (K(d) = 41 nM)
      and weakly inhibited cynomolgus CXCR1-mediated chemotaxis (IC(50) approximately
      1000 nM). Oral treatment with Sch527123 blocked pulmonary neutrophilia (ED(50) =
      1.2 mg/kg) and goblet cell hyperplasia (32-38% inhibition at 1-3 mg/kg) in mice
      following the intranasal lipopolysaccharide (LPS) administration. In rats,
      Sch527123 suppressed the pulmonary neutrophilia (ED(50) = 1.8 mg/kg) and increase
      in bronchoalveolar lavage (BAL) mucin content (ED(50) =<0.1 mg/kg) induced by
      intratracheal (i.t.) LPS. Sch527123 also suppressed the pulmonary neutrophilia
      (ED(50) = 1.3 mg/kg), goblet cell hyperplasia (ED(50) = 0.7 mg/kg), and increase
      in BAL mucin content (ED(50) = <1 mg/kg) in rats after i.t. administration of
      vanadium pentoxide. In cynomolgus monkeys, Sch527123 reduced the pulmonary
      neutrophilia induced by repeat bronchoscopy and lavage (ED(50) = 0.3 mg/kg).
      Therefore, Sch527123 may offer benefit for the treatment of inflammatory lung
      disorders in which pulmonary neutrophilia and mucus hypersecretion are important
      components of the underlying disease pathology.

PMID- 17496166
TI  - Pharmacological characterization of Sch527123, a potent allosteric CXCR1/CXCR2
      antagonist.
AB  - In neutrophils, growth-related protein-alpha (CXCL1) and interleukin-8 (CXCL8),
      are potent chemoattractants (Cytokine 14:27-36, 2001; Biochemistry 42:2874-2886,
      2003) and can stimulate myeloperoxidase release via activation of the G protein
      coupled receptors CXCR1 and CXCR2. The role of CXCR1 and CXCR2 in the
      pathogenesis of inflammatory responses has encouraged the development of small
      molecule antagonists for these receptors. The data presented herein describe the
      pharmacology of 2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5-methyl-furan-2-yl)
      propyl]amino]-3,4-dioxo-cyclobut-1-enylamino}-benzamide (Sch527123), a novel
      antagonist of both CXCR1 and CXCR2. Sch527123 inhibited chemokine binding to (and
      activation of) these receptors in an insurmountable manner and, as such, is
      categorized as an allosteric antagonist. Sch527123 inhibited neutrophil
      chemotaxis and myeloperoxidase release in response to CXCL1 and CXCL8 but had no
      effect on the response of these cells to C5a or formyl-methionyl-leucyl
      phenylalanine. The pharmacological specificity of Sch527123 was confirmed by
      testing in a diversity profile against a panel of enzymes, channels, and
      receptors. To measure compound affinity, we characterized [(3)H]Sch527123 in both
      equilibrium and nonequilibrium binding analyses. Sch527123 binding to CXCR1 and
      CXCR2 was both saturable and reversible. Although Sch527123 bound to CXCR1 with
      good affinity (K(d) = 3.9 +/- 0.3 nM), the compound is CXCR2-selective (K(d) =
      0.049 +/- 0.004 nM). Taken together, our data show that Sch527123 represents a
      novel, potent, and specific CXCR2 antagonist with potential therapeutic utility
      in a variety of inflammatory conditions.

PMID- 17496167
TI  - Reciprocal regulation of endothelial nitric-oxide synthase and NADPH oxidase by
      betulinic acid in human endothelial cells.
AB  - Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is a protective
      principle in the vasculature. Many cardiovascular diseases are associated with
      reduced NO bioactivity and eNOS uncoupling due to oxidative stress. Compounds
      that reverse eNOS uncoupling and increase eNOS expression are of therapeutic
      interest. Zizyphi Spinosi semen (ZSS) is one of the most widely used traditional
      Chinese herbs with protective effects on the cardiovascular system. In human
      umbilical vein endothelial cells (HUVEC) and HUVEC-derived EA.hy 926 cells, an
      extract of ZSS increased eNOS promoter activity, eNOS mRNA and protein
      expression, and NO production in a concentration- and time-dependent manner.
      Major ZSS constituents include saponins, such as jujuboside A and B, and
      pentacyclic triterpenes, such as betulin and betulinic acid. Jujuboside A,
      jujuboside B, or betulin had no significant effect on eNOS expression, whereas
      betulinic acid increased eNOS mRNA and protein expression in HUVEC and EA.hy 926
      cells. Interestingly, betulinic acid also attenuated the expression of NADPH
      oxidase subunits Nox4 and p22phox, thereby reducing oxidative stress and
      improving eNOS function. Consequently, betulinic acid-treated endothelial cells
      showed an increased production of bioactive NO (as indicated by a higher efficacy
      in stimulating cGMP generation in RFL-6 reporter cells). Thus, betulinic acid
      possesses combined properties of eNOS up-regulation and NADPH oxidase down
      regulation. Compounds such as betulinic acid may have a therapeutic potential in
      cardiovascular disease.

PMID- 17496168
TI  - Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a
      novel drug candidate for amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      characterized by progressive death of cortical and spinal motor neurons, for
      which there is no effective treatment. Using a cell-based assay for compounds
      capable of preventing motor neuron cell death in vitro, a collection of
      approximately 40,000 low-molecular-weight compounds was screened to identify
      potential small-molecule therapeutics. We report the identification of cholest-4
      en-3-one, oxime (TRO19622) as a potential drug candidate for the treatment of
      ALS. In vitro, TRO19622 promoted motor neuron survival in the absence of trophic
      support in a dose-dependent manner. In vivo, TRO19622 rescued motor neurons from
      axotomy-induced cell death in neonatal rats and promoted nerve regeneration
      following sciatic nerve crush in mice. In SOD1(G93A) transgenic mice, a model of
      familial ALS, TRO19622 treatment improved motor performance, delayed the onset of
      the clinical disease, and extended survival. TRO19622 bound directly to two
      components of the mitochondrial permeability transition pore: the voltage
      dependent anion channel and the translocator protein 18 kDa (or peripheral
      benzodiazepine receptor), suggesting a potential mechanism for its
      neuroprotective activity. TRO19622 may have therapeutic potential for ALS and
      other motor neuron and neurodegenerative diseases.

PMID- 17496170
TI  - Enhancing the international status of academic psychiatry.

PMID- 17496169
TI  - Building individualized medicine: prevention of adverse reactions to warfarin
      therapy.
AB  - Warfarin is the most widely used oral anticoagulant in the world for patients
      with venous thrombosis, pulmonary embolism, chronic atrial fibrillation, and
      prosthetic heart valves. Approximately 30 genes contribute to therapeutic effects
      of warfarin, and genetic polymorphisms in these genes may modulate its
      anticoagulant activity. In contrast to monogenic pharmacogenetic traits, warfarin
      drug response is a polygenic trait, and development of diagnostic tools
      predictive of adverse reactions to warfarin requires a novel approach. A
      combination of two strategies, biochemical isolation of allelic variants and
      linkage disequilibrium association studies, was used to find an association
      between genetic polymorphisms in the candidate genes and warfarin response. A
      strong association was found between genetic polymorphisms in six genes,
      including VKORC1, CYP2C9, PROC, EPHX1, GGCX, and ORM1, and interindividual
      variability in the anticoagulant effect of warfarin; the strongest predictors
      were VKORC1 and CYP2C9. Generation of single nucleotide polymorphism (SNP)-based
      dense genetic maps made it possible to identify haplotypes associated with
      drugresponse phenotypes. Discrimination between haplotypes associated with
      warfarin dose phenotypes can be achieved by a limited set of informative
      polymorphisms (tag SNPs). The use of tag SNPs in pharmacogenomic analysis
      provides a promising tool for dissecting polygenic traits of drug response.

PMID- 17496171
TI  - Hurricane Katrina: disasters teach us and we must learn.

PMID- 17496172
TI  - In the eye of Katrina: surviving the storm and rebuilding an academic department
      of psychiatry.

PMID- 17496173
TI  - Opportunity missed: a lesson learned from evacuating mentally ill patients
      following Hurricanes Katrina and Rita.

PMID- 17496174
TI  - Lessons learned from Katrina: one department's perspective.

PMID- 17496175
TI  - Katrina relief: lessons for the academic medical center.

PMID- 17496176
TI  - Psychiatric issues and answers following Hurricane Katrina.

PMID- 17496177
TI  - Medical student education in psychiatry after Katrina: disaster and renewal.

PMID- 17496178
TI  - Improving the pedagogy associated with the teaching of psychopharmacology.
AB  - OBJECTIVE: The authors summarize two special sessions focused on the teaching of
      psychopharmacology at the 2003 and 2004 annual meeting of the American College of
      Neuropsychopharmacology (ACNP). The focus was on whether "improving the teaching
      learning process" in psychiatric residency programs could improve clinical
      practice. METHOD: Problems of strategies and pedagogic techniques that have been
      used were presented from multiple perspectives (e.g., from a dean, department
      chair, training director, and former students). CONCLUSIONS: There was a
      consensus that action involving psychopharmacology organizations and the American
      Association of Directors of Residency Training in Psychiatry (AADPRT) was
      necessary to improve "evidence-based" competencies before graduation and to
      follow prescribing patterns into clinical practice to determine whether the
      standards of care could be improved.

PMID- 17496179
TI  - Use of dialectical behavior therapy in borderline personality disorder: a view
      from residency.
AB  - OBJECTIVE: The authors describe the use of dialectical behavior therapy (DBT) in
      treating borderline personality disorder during psychiatry residency, and assess
      the status of DBT education within psychiatry residencies in the United States.
      METHOD: The authors present a patient with borderline personality disorder
      treated by a resident using DBT, along with perspectives from the resident's
      supervisors. Additionally, self-report surveys inquiring about the attitudes and
      experiences of residency directors and PGY-4 residents regarding DBT were sent to
      program directors with available e-mail addresses on FREIDA online. RESULTS: The
      DBT method employed by the resident had to be modified to fit the constraints of
      a residency program. The patient in therapy had a tumultuous course, ultimately
      resulting in the discontinuation of treatment. Survey results suggested an
      underemphasis on the education and use of DBT during residency, though the
      strength of this conclusion is limited by the small proportion of surveys
      returned. CONCLUSIONS: Achieving the efficacy of DBT-based treatment of
      borderline personality disorder reported in the literature in the setting of a
      residency program is challenging. Greater exposure to DBT during residency may
      increase residents' skills in using the technique and the likelihood that they
      will use it after residency.

PMID- 17496180
TI  - Medical students' interest in child psychiatry: a clerkship intervention.
AB  - OBJECTIVE: The authors examine the efficacy of a brief presentation to enhance
      clerkship student interest in child and adolescent psychiatry as a career choice.
      METHOD: Attitudes of students attending a brief presentation on the positive
      aspects of child psychiatry were compared with those of non-attenders. RESULTS:
      Students who attended the presentation were more accurate in reporting salaries
      and acknowledging a shortage in the field. Their interest in child and adolescent
      psychiatry as a career choice, however, did not change. Student interest was
      related to having had prior contact with a psychiatrist, whereas decreased
      interest was related to having an adult-only experience during the clerkship.
      CONCLUSIONS: A brief presentation can be effective in changing certain factual
      perceptions about child and adolescent psychiatry but may be ineffective in
      enhancing medical students' interest in it. However, exposure to child patients
      during the clerkship may prevent a decline in student interest in the field.

PMID- 17496181
TI  - A practical approach to implementing the core competencies in a child and
      adolescent psychiatry residency program.
AB  - OBJECTIVE: The authors describe the development and implementation of the
      Accreditation Council for Graduate Medical Education's core competencies in a
      child and adolescent psychiatry residency program. METHOD: The authors identify
      the program's organizational approach and participants and detail various
      strategies and methods of defining, describing, and utilizing the core
      competencies, with an emphasis on using practical, easily employed techniques
      within existing systems and structures. RESULTS: Using this approach to
      developing and implementing the core competencies was effective and accepted well
      by the participants. CONCLUSIONS: Existing program structures and systems can be
      used successfully to develop and implement the core competencies in a residency
      program.

PMID- 17496182
TI  - Psychiatric education: does it affect stigma?

PMID- 17496183
TI  - Should we be teaching philosophy to psychiatrists-in-training?

PMID- 17496184
TI  - Ligers lived.

PMID- 17496186
TI  - Napoleon Dynamite has Asperger's? Gosh, It's called cultural competence, you
      freakin' idiots.

PMID- 17496188
TI  - Best of the web in pathology: a practical guide to finding specific pathology
      resources on the internet.
AB  - BACKGROUND: Although a large number of pathology-specific websites (PSWs) are
      accessible on the internet, the potential use of PSWs is relatively unknown among
      pathologists. As a PSW-directory does not exist, it may be difficult to find
      certain resources that are scattered over the internet. AIMS: To critically
      revisit PSWs in order to create a collection of selected websites that may be
      useful for practising pathologists worldwide. METHODS: Using special medical
      databases and link collections, extensive search for PSWs was performed on the
      world wide web. Each website was evaluated with regard to content and practical
      use for pathologists. RESULTS: PSWs contain electronic training manuals,
      journals, case collections, photo-archives, link directories, or slide
      collections of virtual microscopy. PSWs offer lavishly illustrated education
      material for undergraduates and postgraduates in pathology, but may also be very
      useful as reference books or as an instrument of continuing medical education for
      experienced pathologists. The paper shows how to find PSWs, and presents an
      annotated list of 100 of the best PSWs. CONCLUSIONS: PSWs as a whole form a
      heterogeneous patchwork of information. It is suggested that a central catalogue
      listing all PSWs that are available worldwide be established. This database would
      enable pathologists to have immediate access to all up-to-date pathology-specific
      resources on the internet, without the need to perform any laborious web research
      for themselves. It is hoped that in the future, the repertoire of on-line
      resources in pathology will be systematically perfected. The internet will then
      play a central role in the daily practice of pathologists as a medium of
      information and communication.

PMID- 17496187
TI  - Best practice in primary care pathology: review 10.
AB  - This tenth best practice review examines four series of common primary care
      questions in laboratory medicine: (i) antenatal testing in pregnant women; (ii)
      estimated glomerular filtration rate calculation; (iii) safety testing for
      methotrexate; and (iv) blood glucose measurement in diabetes. The review is
      presented in question-answer format, referenced for each question series. The
      recommendations represent a precis of guidance found using a standardised
      literature search of national and international guidance notes, consensus
      statements, health policy documents and evidence-based medicine reviews,
      supplemented by Medline Embase searches to identify relevant primary research
      documents. They are not standards but form a guide to be set in the clinical
      context. Most are consensus rather than evidence-based. They will be updated
      periodically to take account of new information.

PMID- 17496189
TI  - Development of real time PCR to detect Toxoplasma gondii and Borrelia burgdorferi
      infections in postal samples.
AB  - BACKGROUND: Most of the samples sent to reference laboratories are delivered by
      post. Thus, diagnostic PCR tests on blood samples have to be performed using
      methods which are optimised and validated for such conditions. There is a low
      probability that the organisms Toxoplasma gondii and Borrelia burgdorferi will be
      present. AIM: To confirm that robotic extraction methods followed by real time
      PCR will detect as little as one organism/test sample in postal specimens.
      METHODS: Human blood samples spiked with decreasing numbers of each organism
      (range 10(5)-1/per extract) were extracted using two commercial kits on a Qiagen
      BioRobot EZ1 Workstation. Extracts of whole blood and blood fractions were tested
      by real time PCR. The effect of storage of blood for 1-6 days at room temperature
      was also investigated. RESULTS: Maximum sensitivity (1 organism/test sample) was
      achieved for T gondii with either extraction method; the sensitivity for B
      burgdorferi was between 1 and 10 organisms/test. Whole blood was the most
      suitable sample to extract, as both organisms were as likely to be detectable in
      the red cell as the white cell fraction. Sensitivity was not reduced by storing
      spiked samples at room temperature for up to 6 days. Inhibitory effects on PCR
      were not a significant problem provided that samples were extracted using the
      blood extraction kit. CONCLUSIONS: Using appropriate robotic extraction methods,
      both T gondii and B burgdorferi can be detected by real time PCR with near
      maximum possible sensitivity in whole blood samples. Blood samples can be
      transferred to reference laboratories by post without loss of sensitivity over
      the likely transit period.

PMID- 17496190
TI  - Diagnostic value of combining immunostaining for CD3 and nuclear morphometry in
      mycosis fungoides.
AB  - BACKGROUND: Mycosis fungoides (MF) is the most common skin lymphoid neoplasm. In
      initial stages, differential diagnosis of MF from other benign dermal lymphoid
      infiltrates (BDLI) may be impossible on morphological basis alone. In previous
      studies, only deletion of CD7 in MF proved to be of diagnostic help, but not the
      ratio between immunoexpression of CD4 and CD8. METHODS: 30 cases of MF and 11
      cases of BDLI were analysed, in order to compare morphometric parameters, which
      could be of diagnostic aid. As CD7 is frequently deleted in MF,
      immunohistochemical detection of T-cells was made using an antibody to CD3.
      Images of 100 CD3-positive cells per case in both groups were captured and
      analysed using a simple computer program for nuclear perimeter, area, diameter
      and nuclear contour index. RESULTS: All parameters showed statistically
      significant higher values for MF. Area was the variable with the strongest
      discriminating power between the two groups of patients. Thus even if
      morphological evaluation is not accurate to distinguish benign versus malignant
      dermal lymphoid infiltrates, due to the variability of size and shape of these
      cells, a more sensitive method promptly shows this difference. CONCLUSION:
      Results suggest that morphometry of CD3-positive lymphoid cells may add valuable
      information in the differential diagnosis of MF and benign dermatoses.

PMID- 17496191
TI  - Demystifying basal-like breast carcinomas.
AB  - "Basal" breast cancers are dominating the breast research literature at present
      and pathologists are under increasing pressure to evaluate for such a phenotype
      by their surgical and oncological colleagues. There is also much confusion about
      how to assess cancers, which immunohistochemical markers to use, what meaning and
      benefit this provides, and what the surgeons and oncologists will do with the
      information. Much remains to be done to answer all these questions but here we
      try to shed light on some of the issues and suggest what is still to come.

PMID- 17496192
TI  - Multiple myeloma with bone marrow extracellular crystal deposition.

PMID- 17496193
TI  - The effect of automated test rejection on repeat requesting.

PMID- 17496194
TI  - Differences in ATP7A gene expression underlie intrafamilial variability in Menkes
      disease/occipital horn syndrome.
AB  - BACKGROUND: Pronounced intrafamilial variability is unusual in Menkes disease and
      its variants. We report two unrelated families featuring affected members with
      unusually disparate clinical and biochemical phenotypes and explore the
      underlying molecular mechanisms. METHODS: We measured biochemical markers of
      impaired copper transport in five patients from two unrelated families and used
      RNase protection, quantitative reverse transcription (RT)-PCR, Western blot
      analysis and yeast complementation studies to characterise two ATP7A missense
      mutations, A1362D and S637L. RESULTS: In two brothers (family A) with A1362D,
      RNase protection and Western blot analyses revealed higher amounts of ATP7A
      transcript and protein in the older, mildly affected patient, who also had a
      higher plasma copper level and lower cerebrospinal fluid dihydroxyphenylalanine :
      dihydroxyphenylglycol ratio. These findings indicate greater gastrointestinal
      absorption of copper and higher activity of dopamine-beta-hydroxylase, a copper
      dependent enzyme, respectively. In family B, three males with a missense mutation
      (S637L) in an exon 8 splicing enhancer showed equally reduced amounts of ATP7A
      transcript and protein by quantitative RT-PCR and western blot analysis,
      respectively, despite a more severe phenotype in the youngest. This patient's
      medical history was notable for cardiac arrest as a neonate, to which we
      attribute his more severe neurodevelopmental outcome. CONCLUSIONS: These families
      illustrate that genetic and non-genetic mechanisms may underlie intrafamilial
      variability in Menkes disease and its variants.

PMID- 17496195
TI  - Pregnancy does not influence colonic polyp multiplicity but may modulate upper
      gastrointestinal disease in patients with FAP.
AB  - BACKGROUND: Reproductive factors have been shown by epidemiology studies to alter
      colorectal cancer risk in women. Familial adenomatous polyposis (FAP) patients
      carry a germline adenomatous polyposis coli (APC) mutation predisposing to
      multiple adenoma formation in the intestine. The Min mouse provides a good model
      of FAP, and we recently reported a significant increase in intestinal tumour
      multiplicity in a recombinant line of mice following pregnancy. AIM: We
      considered whether reproduction modulates intestinal tract disease in a large
      cohort of female patients with FAP (n = 180). RESULTS: Multiple regression
      analysis showed that the number of colonic polyps observed was not related to the
      person's pregnancy status nor the position of their APC germline mutation. The
      proportion of women attaining a high Spigelman stage (3 or 4) was unrelated to
      having a pregnancy prior to attaining the maximum Spigelman stage (p = 0.6). On
      the other hand, having a pregnancy significantly increased the proportion of
      women that attained the highest Spigelman stage when their APC germline mutation
      occurred within the mutation cluster region or at or after codon 1020 (50%, 6/12,
      p = 0.005 and 42%, 13/31, p = 0.006, respectively; multivariable logistic
      regression). CONCLUSION: Our data suggest that reproduction may influence disease
      severity in the upper gastrointestinal tract in patients with FAP.

PMID- 17496196
TI  - Mutations of the Birt Hogg Dube gene in patients with multiple lung cysts and
      recurrent pneumothorax.
AB  - RATIONALE: Birt-Hogg-Dube (BHD) syndrome, a rare inherited autosomal
      genodermatosis first recognised in 1977, is characterised by fibrofolliculomas of
      the skin, an increased risk of renal tumours and multiple lung cysts with
      spontaneous pneumothorax. The BHD gene, a tumour suppressor gene located at
      chromosome 17p11.2, has recently been shown to be defective. Recent genetic
      studies revealed that clinical pictures of the disease may be variable and may
      not always present the full expression of the phenotypes. OBJECTIVES: We
      hypothesised that mutations of the BHD gene are responsible for patients who have
      multiple lung cysts of which the underlying causes have not yet been elucidated.
      METHODS: We studied eight patients with lung cysts, without skin and renal
      disease; seven of these patients have a history of spontaneous pneumothorax and
      five have a family history of pneumothorax. The BHD gene was examined using PCR,
      denaturing high-performance liquid chromatography and direct sequencing. MAIN
      RESULTS: We found that five of the eight patients had a BHD germline mutation.
      All mutations were unique and four of them were novel, including three different
      deletions or insertions detected in exons 6, 12 and 13, respectively and one
      splice acceptor site mutation in intron 5 resulting in an in-frame deletion of
      exon 6. CONCLUSIONS: We found that germline mutations of the BHD gene are
      involved in some patients with multiple lung cysts and pneumothorax.
      Pulmonologists should be aware that BHD syndrome can occur as an isolated
      phenotype with pulmonary involvement.

PMID- 17496197
TI  - Coordinated transcriptional regulation patterns associated with infertility
      phenotypes in men.
AB  - INTRODUCTION: Microarray gene-expression profiling is a powerful tool for global
      analysis of the transcriptional consequences of disease phenotypes. Understanding
      the genetic correlates of particular pathological states is important for more
      accurate diagnosis and screening of patients, and thus for suggesting appropriate
      avenues of treatment. As yet, there has been little research describing gene
      expression profiling of infertile and subfertile men, and thus the underlying
      transcriptional events involved in loss of spermatogenesis remain unclear. Here
      we present the results of an initial screen of 33 patients with differing
      spermatogenic phenotypes. METHODS: Oligonucleotide array expression profiling was
      performed on testis biopsies for 33 patients presenting for testicular sperm
      extraction. Significantly regulated genes were selected using a mixed model
      analysis of variance. Principle components analysis and hierarchical clustering
      were used to interpret the resulting dataset with reference to the patient
      history, clinical findings and histological composition of the biopsies. RESULTS:
      Striking patterns of coordinated gene expression were found. The most significant
      contains multiple germ cell-specific genes and corresponds to the degree of
      successful spermatogenesis in each patient, whereas a second pattern corresponds
      to inflammatory activity within the testis. Smaller-scale patterns were also
      observed, relating to unique features of the individual biopsies.

PMID- 17496198
TI  - Insulin-degrading enzyme is genetically associated with Alzheimer's disease in
      the Finnish population.
AB  - The gene for insulin-degrading enzyme (IDE), which is located at chromosome
      10q24, has been previously proposed as a candidate gene for late-onset
      Alzheimer's disease (AD) based on its ability to degrade amyloid beta-protein.
      Genotyping of single nucleotide polymorphisms (SNPs) in the IDE gene in Finnish
      patients with AD and controls revealed SNPs rs4646953 and rs4646955 to be
      associated with AD, conferring an approximately two-fold increased risk. Single
      locus findings were corroborated by the results obtained from haplotype analyses.
      This suggests that genetic alterations in or near the IDE gene may increase the
      risk for developing AD.

PMID- 17496199
TI  - Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3
      mediated induction of microRNA-21 through a highly conserved enhancer.
AB  - Signal transducer and activator of transcription 3 (Stat3) is implicated in the
      pathogenesis of many malignancies and essential for IL-6-dependent survival and
      growth of multiple myeloma cells. Here, we demonstrate that the gene encoding
      oncogenic microRNA-21 (miR-21) is controlled by an upstream enhancer containing 2
      Stat3 binding sites strictly conserved since the first observed evolutionary
      appearance of miR-21 and Stat3. MiR-21 induction by IL-6 was strictly Stat3
      dependent. Ectopically raising miR-21 expression in myeloma cells in the absence
      of IL-6 significantly reduced their apoptosis levels. These data provide strong
      evidence that miR-21 induction contributes to the oncogenic potential of Stat3.

PMID- 17496200
TI  - Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for
      chronic myeloid leukemia.
AB  - Mutations in the kinase domain (KD) of BCR-ABL are the most prevalent mechanism
      of acquired imatinib resistance in patients with chronic myeloid leukemia (CML).
      Here we examine predisposing factors underlying acquisition of KD mutations,
      evidence for acquisition of mutations before and during therapy, and whether the
      detection of a KD mutation universally implies resistance. We also provide a
      perspective on how the second-line Abl inhibitors dasatinib and nilotinib are
      faring in the treatment of imatinib-resistant CML, especially in relation to
      specific KD mutations. We discuss the growing importance of the multi-inhibitor
      resistant 315T>I mutant and the therapeutic potential that a 315T>I inhibitor
      would have. Last, we assess the potential of Abl kinase inhibitor combinations to
      induce stable responses even in advanced CML and interpret the emerging data in
      the context of CML pathogenesis.

PMID- 17496201
TI  - Dasatinib induces rapid hematologic and cytogenetic responses in adult patients
      with Philadelphia chromosome positive acute lymphoblastic leukemia with
      resistance or intolerance to imatinib: interim results of a phase 2 study.
AB  - Patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia
      (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral,
      multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously
      induced responses in patients with imatinib-resistant or -intolerant Ph-positive
      ALL. We present the interim results of a phase 2 study designed to further assess
      the efficacy, safety, and tolerability of dasatinib 140 mg in this patient
      population (n = 36). With a minimum follow-up of 8 months, treatment with
      dasatinib resulted in substantial hematologic and cytogenetic response rates.
      Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom
      remained progression-free. Complete cytogenetic responses were attained by 58%
      (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib
      resistance did not preclude a response to dasatinib. Dasatinib was also
      tolerable, with 6% (2/36) of patients discontinuing therapy as a result of study
      drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile neutropenia
      was the most frequent severe AE, but this and other cytopenias were manageable
      with dose reduction. Dasatinib represents a safe and effective treatment option
      and an important therapeutic advance for patients with Ph-positive ALL. This
      trial was registered at www.clinicaltrials.gov as #CA180015.

PMID- 17496202
TI  - Stable differentiation and clonality of murine long-term hematopoiesis after
      extended reduced-intensity selection for MGMT P140K transgene expression.
AB  - Efficient in vivo selection increases survival of gene-corrected hematopoietic
      stem cells (HSCs) and protects hematopoiesis, even if initial gene transfer
      efficiency is low. Moreover, selection of a limited number of transduced HSCs
      lowers the number of cell clones at risk of gene activation by insertional
      mutagenesis. However, a limited clonal repertoire greatly increases the
      proliferation stress of each individual clone. Therefore, understanding the
      impact of in vivo selection on proliferation and lineage differentiation of stem
      cell clones is essential for its clinical use. We established minimal cell and
      drug dosage requirements for selection of P140K mutant O6-methylguanine-DNA
      methyltransferase (MGMT P140K)-expressing HSCs and monitored their
      differentiation potential and clonality under long-term selective stress. Up to
      17 administrations of O6-benzylguanine (O6-BG) and 1,3-bis(2-chloroethyl)-1
      nitroso-urea (BCNU) did not impair long-term differentiation and proliferation of
      MGMT P140K-expressing stem-cell clones in mice that underwent serial
      transplantation and did not lead to clonal exhaustion. Interestingly, not all
      gene-modified hematopoietic repopulating cell clones were efficiently selectable.
      Our studies demonstrate that the normal function of murine hematopoietic stem and
      progenitor cells is not compromised by reduced-intensity long-term in vivo
      selection, thus underscoring the potential value of MGMT P140K selection for
      clinical gene therapy.

PMID- 17496203
TI  - Dosage-dependent requirement of BMP type II receptor for maintenance of vascular
      integrity.
AB  - Germ-line mutations in bone morphogenic protein type II receptor (Bmpr2) confer
      susceptibility to pulmonary arterial hypertension (PAH), which is characterized
      by obstructive vascular lesions in small arteries. The molecular and cellular
      mechanisms that account for the etiology of this disorder remain elusive, as does
      the role of Bmpr2 in postnatal tissue homeostasis. Here we show that in adult
      mice, stably silencing Bmpr2 expression by RNA interference does not increase
      pulmonary arterial resistance but results in severe mucosal hemorrhage,
      incomplete mural cell coverage on vessel walls, and gastrointestinal hyperplasia.
      We present evidence that BMP receptor signaling regulates vascular remodeling
      during angiogenesis by maintaining the expression of endothelial guidance
      molecules that promote vessel patterning and maturation and by counteracting
      growth factor-induced AKT activation. Attenuation of this function may cause
      vascular dysmorphogenesis and predisposition to angioproliferative diseases. Our
      findings provide a mechanistic link between PAH and other diseases associated
      with the BMP/TGF-beta pathways, such as hereditary hemorrhagic telangiectasia and
      juvenile polyposis syndrome.

PMID- 17496205
TI  - Metabolism, distribution and excretion of a selective N-methyl-D-aspartate
      receptor antagonist, traxoprodil, in rats and dogs.
AB  - Disposition of traxoprodil ({1-[2-hydroxy-2-(4-hydroxy-phenyl)-1-methyl-ethyl]-4
      phenyl-piperidin-4-ol}mesylate; TRX), a selective antagonist of the N-methyl-d
      aspartate class of glutamate receptors, was investigated in rats and dogs after
      administration of a single i.v. bolus dose of [(14)C]TRX. Total mean recoveries
      of the radiocarbon were 92.5 and 88.2% from rats and dogs, respectively.
      Excretion of radioactivity was rapid and nearly complete within 48 h after dosing
      in both species. Whole-body autoradioluminography study suggested that TRX
      radioactivity was retained more by uveal tissues, kidney, and liver than by other
      tissues. TRX is extensively metabolized in rats and dogs since only 8 to 15% of
      the administered radioactivity was excreted as unchanged drug in the urine of
      these species. The metabolic pathways included aromatic hydroxylation at the
      phenylpiperidinol moiety, hydroxylation at the hydroxyphenyl ring, and O
      glucuronidation. There were notable species-related qualitative and quantitative
      differences in the metabolism of TRX in rats and dogs. The hydroxylation at the 3
      position of the phenol ring followed by methylation of the resulting catechol
      intermediate and subsequent conjugation were identified as the main metabolic
      pathways in dogs. In contrast, formation of the major metabolites in rats was due
      to oxidation at the 4'-position of the phenylpiperidinol moiety followed by
      further oxidation and phase II conjugation. TRX glucuronide conjugate was
      identified as the major circulating component in rats, whereas the glucuronide
      and sulfate conjugates of O-methyl catechol metabolite were the major metabolites
      in dog plasma. The site of conjugation of regioisomeric glucuronides was
      established from the differences in the collision-induced dissociation product
      ion spectra of their methylated products.

PMID- 17496206
TI  - Kinetics of valproic acid glucuronidation: evidence for in vivo autoactivation.
AB  - Sigmoidal or autoactivation kinetics has been observed in vitro for both
      cytochrome P450- and UDP-glucuronosyltransferase-catalyzed enzymatic reactions.
      However, the in vivo relevance of sigmoidal kinetics has never been clearly
      demonstrated. In the current study we investigate the kinetics of valproic acid
      glucuronide (VPAG) formation both in vivo in adult sheep and in vitro in sheep
      liver microsomes (pool of 10). After a 100 mg/kg i.v. bolus dose of valproic acid
      (VPA) to adult sheep (n = 5), the majority of the dose was recovered in urine as
      VPAG (approximately 79%). Eadie-Hofstee plots of the VPAG formation rate
      (calculated from urinary excretion rate data for VPAG) were characteristic of
      autoactivation kinetics and provided estimates of the apparent maximum velocity
      of an enzymatic reaction (V(max)(app)), the substrate concentration resulting in
      50% of V(max)(app) (S(50)(app)), and Hill coefficient (n) of 2.10 +/- 0.75
      micromol/min/kg, 117 +/- 56 microM, and 1.34 +/- 0.14, respectively. Comparable
      estimates of V(max)(app) (2.63 +/- 0.33 micromol/min/kg), S(50)(app) (118 +/- 53
      microM), and n (2.06 +/- 0.47) describing overall VPA elimination from plasma
      were obtained by fitting VPA unbound plasma concentration-time data to a two
      compartment model with elimination described by the Hill equation. Consistent
      with our in vivo observations, Eadie-Hofstee plots of VPAG formation in sheep
      liver microsomes were characteristic of autoactivation kinetics. To our
      knowledge, these data provide the first clear demonstration that autoactivation
      kinetics observed in vitro in liver preparations can translate to the in vivo
      situation at least under certain experimental conditions and confirm its
      relevance.

PMID- 17496204
TI  - Trousseau's syndrome: multiple definitions and multiple mechanisms.
AB  - In 1865, Armand Trousseau noted that unexpected or migratory thrombophlebitis
      could be a forewarning of an occult visceral malignancy. An analysis by Sack and
      colleagues in 1977 extended the term Trousseau's syndrome to include chronic
      disseminated intravascular coagulopathy associated with microangiopathy,
      verrucous endocarditis, and arterial emboli in patients with cancer, often
      occurring with mucin-positive carcinomas. In recent times the term has been
      ascribed to various clinical situations, ranging all the way from these classic
      descriptions to any kind of coagulopathy occurring in the setting of any kind of
      malignancy. These multiple definitions of Trousseau's syndrome are partly the
      consequence of multiple pathophysiologic mechanisms that apparently contribute to
      the hypercoagulability associated with cancer. Even the classic syndrome probably
      represents a spectrum of disorders, ranging from exaggerated fluid-phased
      thrombosis dependent on prothrombotic agents such as tissue factor to a platelet-
      and endotheliumum-based selectin-dependent microangiopathy associated with mucin
      producing carcinomas, along with thrombin and fibrin production. Also considered
      here are recent hypotheses about genetic pathways within tumor cells that might
      trigger these thrombotic phenomena, and the reasons why therapy with heparins of
      various kinds remain the preferred treatment, probably because of their salutary
      actions on several of the proposed pathologic mechanisms.

PMID- 17496207
TI  - Expression of thirty-six drug transporter genes in human intestine, liver,
      kidney, and organotypic cell lines.
AB  - This study was designed to quantitatively assess the mRNA expression of 36
      important drug transporters in human jejunum, colon, liver, and kidney.
      Expression of these transporters in human organs was compared with expression in
      commonly used cell lines (Caco-2, HepG2, and Caki-1) originating from these
      organs to assess their value as in vitro transporter system models, and was also
      compared with data obtained from the literature on expression in rat tissues to
      assess species differences. Transporters that were highly expressed in the
      intestine included HPT1, PEPT1, BCRP, MRP2, and MDR1, whereas, in the liver,
      OCT1, MRP2, OATP-C, NTCP and BSEP were the main transporters. In the kidney, OAT1
      was expressed at the highest levels, followed by OAT3, OAT4, MCT5, MDR1, MRP2,
      OCT2, and OCTN2. The best agreement between human tissue and the representative
      cell line was observed for human jejunum and Caco-2 cells. Expression in liver
      and kidney ortholog cell lines was not correlated with that in the associated
      tissue. Comparisons with rat transporter gene expression revealed significant
      species differences. Our results allowed a comprehensive quantitative comparison
      of drug transporter expression in human intestine, liver, and kidney. We suggest
      that it would be beneficial for predictive pharmacokinetic research to focus on
      the most highly expressed transporters. We hope that our comparison of rat and
      human tissue will help to explain the observed species differences in in vivo
      models, increase understanding of the impact of active transport processes on
      pharmacokinetics and distribution, and improve the quality of predictions from
      animal studies to humans.

PMID- 17496208
TI  - Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic
      uptake as the common mechanism of its interactions with cyclosporin A,
      rifampicin, and sildenafil.
AB  - The elimination process of the endothelin receptor antagonist bosentan (Tracleer)
      in humans is entirely dependent on metabolism mediated by two cytochrome P450
      (P450) enzymes, i.e., CYP3A4 and CYP2C9. Most interactions with concomitantly
      administered drugs can be rationalized in terms of inhibition of these P450
      enzymes. The increased bosentan concentrations observed in the presence of
      cyclosporin A, rifampicin, or sildenafil, however, are incompatible with this
      paradigm and prompted the search for alternative mechanisms governing these
      interactions. In the present article, we identify bosentan and its active plasma
      metabolite, Ro 48-5033 (4-(2-hydroxy-1,1-dimethyl-ethyl)-N-[6-(2-hydroxy-ethoxy)
      5-(2-methoxy-phenoxy)-[2,2']bipyrimidinyl-4-yl]-benzenesulfonamide), as
      substrates of the human organic anion transporting polypeptides (OATP) OATP1B1
      and OATP1B3. Bosentan uptake into Chinese hamster ovary cells expressing these
      OATP transporters was efficiently inhibited by cyclosporin A and rifampicin with
      IC(50) values significantly below their effective plasma concentrations in
      humans. The phosphodiesterase-5 inhibitor sildenafil was also shown to interfere
      with OATP-mediated transport, however, at concentrations above those achieved in
      therapeutic use. Therefore, inhibition of bosentan hepatic uptake may represent
      an alternative/complementary mechanism to rationalize some of the pharmacokinetic
      interactions seen in therapeutic use. A similar picture has been drawn for drugs
      like pitavastatin and fexofenadine, drugs that are mainly excreted in unchanged
      form. Bosentan elimination, in contrast, is entirely dependent on metabolism.
      Therefore, the described interactions with rifampicin, cyclosporin A, and, to a
      lesser extent, sildenafil represent evidence that inhibition of hepatic uptake
      may become the rate-limiting step in the overall elimination process even for
      drugs whose elimination is entirely dependent on metabolism.

PMID- 17496209
TI  - Angiotensin-(1 7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat
      heart in vivo: role of the AT1 and Mas receptors.
AB  - Angiotensin (ANG) II exerts a negative modulation on insulin signal transduction
      that might be involved in the pathogenesis of hypertension and insulin
      resistance. ANG-(1-7), an endogenous heptapeptide hormone formed by cleavage of
      ANG I and ANG II, counteracts many actions of ANG II. In the current study, we
      have explored the role of ANG-(1-7) in the signaling crosstalk that exists
      between ANG II and insulin. We demonstrated that ANG-(1-7) stimulates the
      phosphorylation of Janus kinase 2 (JAK2) and insulin receptor substrate (IRS)-1
      in rat heart in vivo. This stimulating effect was blocked by administration of
      the selective ANG type 1 (AT(1)) receptor blocker losartan. In contrast to ANG
      II, ANG-(1-7) stimulated cardiac Akt phosphorylation, and this stimulation was
      blunted in presence of the receptor Mas antagonist A-779 or the
      phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. The specific JAK2
      inhibitor AG-490 blocked ANG-(1-7)-induced JAK2 and IRS-1 phosphorylation but had
      no effect on ANG-(1-7)-induced phosphorylation of Akt, indicating that activation
      of cardiac Akt by ANG-(1-7) appears not to involve the recruitment of JAK2 but
      proceeds through the receptor Mas and involves PI3K. Acute in vivo insulin
      induced cardiac Akt phosphorylation was inhibited by ANG II. Interestingly,
      coadministration of insulin with an equimolar mixture of ANG II and ANG-(1-7)
      reverted this inhibitory effect. On the basis of our present results, we
      postulate that ANG-(1-7) could be a positive physiological contributor to the
      actions of insulin in heart and that the balance between ANG II and ANG-(1-7)
      could be relevant for the association among insulin resistance, hypertension, and
      cardiovascular disease.

PMID- 17496210
TI  - Early changes in rat hearts with developing pulmonary arterial hypertension can
      be detected with three-dimensional electrocardiography.
AB  - The study aim was to assess three-dimensional electrocardiogram (ECG) changes
      during development of pulmonary arterial hypertension (PAH). PAH was induced in
      male Wistar rats (n = 23) using monocrotaline (MCT; 40 mg/kg sc). Untreated
      healthy rats served as controls (n = 5). ECGs were recorded with an orthogonal
      three-lead system on days 0, 14, and 25 and analyzed with dedicated computer
      software. In addition, left ventricular (LV)-to-right ventricular (RV) fractional
      shortening ratio was determined using echocardiography. Invasively measured RV
      systolic pressure was 49 (SD 10) mmHg on day 14 and 64 (SD 10) mmHg on day 25 vs.
      25 (SD 2) mmHg in controls (both P < 0.001). Baseline ECGs of controls and MCT
      rats were similar, and ECGs of controls did not change over time. In MCT rats,
      ECG changes were already present on day 14 but more explicit on day 25: increased
      RV electromotive forces decreased mean QRS-vector magnitude and changed QRS-axis
      orientation. Important changes in action potential duration distribution and
      repolarization sequence were reflected by a decreased spatial ventricular
      gradient magnitude and increased QRS-T spatial angle. On day 25, LV-to-RV
      fractional shortening ratio was increased, and RV hypertrophy was found, but not
      on day 14. In conclusion, developing PAH is characterized by early ECG changes
      preceding RV hypertrophy, whereas severe PAH is marked by profound ECG changes
      associated with anatomical and functional changes in the RV. Three-dimensional
      ECG analysis appears to be very sensitive to early changes in RV afterload.

PMID- 17496211
TI  - Microvascular network remodeling in dura mater of ovariectomized pigs: role for
      angiopoietin-1 in estrogen-dependent control of vascular stability.
AB  - Estrogen is a key regulator of vascular responses and angioadaptation in multiple
      organs and tissues, including brain. However, the consequences of a loss of
      ovarian steroid hormone secretion on the status of microvascular networks in
      brain and meninges are largely unknown. Here, using the perfused dura mater model
      coupled with high-resolution digital epifluorescence and laser scanning confocal
      microscopy and computer-assisted morphometric analysis, we demonstrate that
      cessation of ovarian hormone production causes dramatic vascular remodeling in
      meningeal microvascular networks characterized by a threefold decrease in
      microvessel density and capillary rarefaction and an almost fourfold increase in
      vascular permeability. These changes were accompanied by a significant decrease
      in angiopoietin-1 (Ang-1) expression and Ang-1/Tie-2 ratio (1.4-fold, P < 0.01,
      and 1.5-fold, P < 0.05, respectively) in ovariectomized animals compared with
      intact females, but no changes were detected in the expression of estrogen
      receptors (ER)-alpha and -beta. We conclude that estrogen-dependent control of
      Ang-1 expression plays an important role in stabilizing meningeal microvessel and
      maintaining healthy microvascular networks.

PMID- 17496212
TI  - Tumor necrosis factor-alpha reduces argininosuccinate synthase expression and
      nitric oxide production in aortic endothelial cells.
AB  - Endothelial dysfunction associated with elevated serum levels of TNF-alpha
      observed in diabetes, obesity, and congenital heart disease results, in part,
      from the impaired production of endothelial nitric oxide (NO). Cellular NO
      production depends absolutely on the availability of arginine, substrate of
      endothelial nitric oxide synthase (eNOS). In this report, evidence is provided
      demonstrating that treatment with TNF-alpha (10 ng/ml) suppresses not only eNOS
      expression but also the availability of arginine via the coordinate suppression
      of argininosuccinate synthase (AS) expression in aortic endothelial cells.
      Western blot and real-time RT-PCR demonstrated a significant and dose-dependent
      reduction of AS protein and mRNA when treated with TNF-alpha with a corresponding
      decrease in NO production. Reporter gene analysis demonstrated that TNF-alpha
      suppresses the AS proximal promoter, and EMSA analysis showed reduced binding to
      three essential Sp1 elements. Inhibitor studies suggested that the repression of
      AS expression by TNF-alpha may be mediated, in part, via the NF-kappaB signaling
      pathway. These findings demonstrate that TNF-alpha coordinately downregulates
      eNOS and AS expression, resulting in a severely impaired citrulline-NO cycle. The
      downregulation of AS by TNF-alpha is an added insult to endothelial function
      because of its important role in NO production and in endothelial viability.

PMID- 17496213
TI  - Vasomotor control in mice overexpressing human endothelial nitric oxide synthase.
AB  - Nitric oxide (NO) plays a key role in regulating vascular tone. Mice
      overexpressing endothelial NO synthase [eNOS-transgenic (Tg)] have a 20% lower
      systemic vascular resistance (SVR) than wild-type (WT) mice. However, because
      eNOS enzyme activity is 10 times higher in tissue homogenates from eNOS-Tg mice,
      this in vivo effect is relatively small. We hypothesized that the effect of eNOS
      overexpression is attenuated by alterations in NO signaling and/or altered
      contribution of other vasoregulatory pathways. In isoflurane-anesthetized open
      chest mice, eNOS inhibition produced a significantly greater increase in SVR in
      eNOS-Tg mice compared with WT mice, consistent with increased NO synthesis.
      Vasodilation to sodium nitroprusside (SNP) was reduced, whereas the vasodilator
      responses to phosphodiesterase-5 blockade and 8-bromo-cGMP (8-Br-cGMP) were
      maintained in eNOS-Tg compared with WT mice, indicating blunted responsiveness of
      guanylyl cyclase to NO, which was supported by reduced guanylyl cyclase activity.
      There was no evidence of eNOS uncoupling, because scavenging of reactive oxygen
      species (ROS) produced even less vasodilation in eNOS-Tg mice, whereas after eNOS
      inhibition the vasodilator response to ROS scavenging was similar in WT and eNOS
      Tg mice. Interestingly, inhibition of other modulators of vascular tone
      [including cyclooxygenase, cytochrome P-450 2C9, endothelin, adenosine, and Ca
      activated K(+) channels] did not significantly affect SVR in either eNOS-Tg or WT
      mice, whereas the marked vasoconstrictor responses to ATP-sensitive K(+) and
      voltage-dependent K(+) channel blockade were similar in WT and eNOS-Tg mice. In
      conclusion, the vasodilator effects of eNOS overexpression are attenuated by a
      blunted NO responsiveness, likely at the level of guanylyl cyclase, without
      evidence of eNOS uncoupling or adaptations in other vasoregulatory pathways.

PMID- 17496215
TI  - Hemodynamic consequences of chronic parasympathetic blockade with a peripheral
      muscarinic antagonist.
AB  - Whereas the sympathetic nervous system has a well-established role in blood
      pressure (BP) regulation, it is not clear whether long-term levels of BP are
      affected by parasympathetic function or dysfunction. We tested the hypothesis
      that chronic blockade of the parasympathetic nervous system has sustained effects
      on BP, heart rate (HR), and BP variability (BPV). Sprague-Dawley rats were
      instrumented for monitoring of BP 22-h per day by telemetry and housed in
      metabolic cages. After the rats healed from surgery and a baseline control
      period, scopolamine methyl bromide (SMB), a peripheral muscarinic antagonist, was
      infused intravenously for 12 days. This was followed by a 10-day recovery period.
      SMB induced a rapid increase in mean BP from 98 +/- 2 mmHg to a peak value of 108
      +/- 2 mmHg on day 2 of the SMB infusion and then stabilized at a plateau value of
      +3 +/- 1 mmHg above control (P < 0.05). After cessation of the infusion, the mean
      BP fell by 6 +/- 1 mmHg. There was an immediate elevation in HR that remained
      significantly above control on the last day of SMB infusion. SMB also induced a
      decrease in short-term (within 30-min periods) HR variability and an increase in
      both short-term and long-term (between 30-min periods) BPV. The data suggest that
      chronic peripheral muscarinic blockade leads to modest, but sustained, increases
      in BP, HR, and BPV, which are known risk factors for cardiovascular morbidity.

PMID- 17496214
TI  - Inhibition of p38 MAPK and AMPK restores adenosine-induced cardioprotection in
      hearts stressed by antecedent ischemia by altering glucose utilization.
AB  - p38 mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase
      (AMPK) are activated by metabolic stresses and are implicated in the regulation
      of glucose utilization and ischemia-reperfusion (IR) injury. This study tested
      the hypothesis that inhibition of p38 MAPK restores the cardioprotective effects
      of adenosine in stressed hearts by preventing activation of AMPK and the
      uncoupling of glycolysis from glucose oxidation. Working rat hearts were perfused
      with Krebs solution (1.2 mM palmitate, 11 mM [(3)H/(14)C]glucose, and 100 mU/l
      insulin). Hearts were stressed by transient antecedent IR (2 x 10 min I/5 min R)
      before severe IR (30 min I/30 min R). Hearts were treated with vehicle, p38 MAPK
      inhibitor (SB-202190, 10 microM), adenosine (500 microM), or their combination
      before severe IR. After severe IR, the phosphorylation (arbitrary density units)
      of p38 MAPK and AMPK, rates of glucose metabolism (micromol x g dry wt(-1) x min(
      1)), and recovery of left ventricular (LV) work (Joules) were similar in vehicle
      , SB-202190- and adenosine-treated hearts. Treatment with SB-202190 + adenosine
      versus adenosine alone decreased p38 MAPK (0.03 +/- 0.01, n = 3 vs. 0.48 +/-
      0.10, n = 3, P < 0.05) and AMPK (0.00 +/- 0.00, n = 3 vs. 0.26 +/- 0.08, n = 3 P
      < 0.05) phosphorylation. This was accompanied by attenuated rates of glycolysis
      (1.51 +/- 0.40, n = 7 vs. 3.95 +/- 0.65, n = 7, P < 0.05) and H(+) production
      (2.12 +/- 0.76, n = 7 vs. 6.96 +/- 1.48, n = 7, P < 0.05), and increased glycogen
      synthesis (1.91 +/- 0.25, n = 6 vs. 0.27 +/- 0.28, n = 6, P < 0.05) and improved
      recovery of LV work (0.81 +/- 0.08, n = 7 vs. 0.30 +/- 0.15, n = 8, P < 0.05).
      These data indicate that inhibition of p38 MAPK abolishes subsequent
      phosphorylation of AMPK and improves the coupling of glucose metabolism, thereby
      restoring adenosine-induced cardioprotection.

PMID- 17496216
TI  - Systemic alpha-adrenergic and nitric oxide inhibition on basal limb blood flow:
      effects of endurance training in middle-aged and older adults.
AB  - Endurance training improves endothelium-dependent vasodilation, yet it does not
      increase basal blood flow in the legs. We determined the effects of a 3-mo
      aerobic exercise intervention on basal leg blood flow and alpha-adrenergic
      vasoconstriction and nitric oxide (NO) release in seven apparently healthy middle
      aged and older adults (60 +/- 3 yr). Basal femoral artery blood flow (via Doppler
      ultrasound) (pretraining: 354 +/- 29; posttraining: 335 +/- 34 ml/min) and
      vascular conductance did not change significantly with the exercise training.
      Before the exercise intervention, femoral artery blood flow increased 32 +/- 16%
      with systemic alpha-adrenergic blockade (with phentolamine) (P < 0.05), and the
      addition of nitric oxide synthase (NOS) inhibition using N(G)-monomethyl-L
      arginine (L-NMMA) did not affect femoral artery blood flow. After training was
      completed, femoral artery blood flow increased 47 +/- 7% with alpha-adrenergic
      blockade (P < 0.01) and then decreased 18 +/- 7% with the subsequent
      administration of L-NMMA (P < 0.05). Leg vascular conductance showed a greater
      alpha-adrenergic blockade-induced vasodilation (+1.7 +/- 0.5 to +3.0 +/- 0.5
      units, P < 0.05) as well as NOS inhibition-induced vasoconstriction (-0.8 +/- 0.4
      to -2.7 +/- 0.7 units, P < 0.05) after the exercise intervention. Resting plasma
      norepinephrine concentration significantly increased after the training. These
      results suggest that regular aerobic exercise training enhances NO
      bioavailability in middle-aged and older adults and that basal limb blood flow
      does not change with exercise training because of the contrasting influences of
      sympathetic nervous system activity and endothelium-derived vasodilation on the
      vasculature.

PMID- 17496217
TI  - Contribution of mitral annular dynamics to LV diastolic filling with alteration
      in preload and inotropic state.
AB  - Mitral annular (MA) excursion during diastole encompasses a volume that is part
      of total left ventricular (LV) filling volume (LVFV). Altered excursion or area
      variation of the MA due to changes in preload or inotropic state could affect LV
      filling. We hypothesized that changes in LV preload and inotropic state would not
      alter the contribution of MA dynamics to LVFV. Six sheep underwent marker
      implantation in the LV wall and around the MA. After 7-10 days, biplane
      fluoroscopy was used to obtain three-dimensional marker dynamics from sedated,
      closed-chest animals during control conditions, inotropic augmentation with
      calcium (Ca), preload reduction with nitroprusside (N), and vena caval occlusion
      (VCO). The contribution of MA dynamics to total LVFV was assessed using volume
      estimates based on multiple tetrahedra defined by the three-dimensional marker
      positions. Neither the absolute nor the relative contribution of MA dynamics to
      LVFV changed with Ca or N, although MA area decreased (Ca, P < 0.01; and N, P <
      0.05) and excursion increased (Ca, P < 0.01). During VCO, the absolute
      contribution of MA dynamics to LVFV decreased (P < 0.001), based on a reduction
      in both area (P < 0.001) and excursion (P < 0.01), but the relative contribution
      to LVFV increased from 18 +/- 4 to 45 +/- 13% (P < 0.001). Thus MA dynamics
      contribute substantially to LV diastolic filling. Although MA excursion and mean
      area change with moderate preload reduction and inotropic augmentation, the
      contribution of MA dynamics to total LVFV is constant with sizeable magnitude.
      With marked preload reduction (VCO), the contribution of MA dynamics to LVFV
      becomes even more important.

PMID- 17496218
TI  - Immunofluorescence localization of the receptor Mas in cardiovascular-related
      areas of the rat brain.
AB  - The G protein-coupled receptor Mas was recently described as an angiotensin-(1-7)
      [ANG-(1-7)] receptor. In the present study we evaluated the anatomical
      localization of Mas using immunofluorescence in the central nervous system of
      adult male Wistar rats. An abundant labeling was found in the hippocampus,
      amigdala, anterodorsal thalamic nucleus, cortex, and hypoglossal nucleus. More
      importantly, a dense ANG-(1-7) receptor Mas immunoreactivity was observed in
      cardiovascular-related areas of the medulla and forebrain, shown in several
      previous studies as sites for the action of ANG-(1-7) in the brain. A strong
      staining was found in the nucleus of the solitary tract, caudal and rostral
      ventrolateral medulla, inferior olive, parvo and magnocellular portions of the
      paraventricular hypothalamic nucleus, supraoptic nucleus, and lateral preoptic
      area. Furthermore, Mas staining was predominantly present in neurons. At the
      medullary sites, a specific and high-intensity binding for rhodamine-ANG-(1-7)
      was also shown. The specific ANG-(1-7) binding was completely displaced by the
      anti-Mas antibody or by the ANG-(1-7) antagonist, A-779. The data presented
      provide the first anatomical basis for the physiological role of ANG-(1-7)/Mas
      axis in the modulation of different cardiovascular functions and give new
      insights for clarifying the role of ANG-(1-7) in the central nervous system.

PMID- 17496219
TI  - Atrioventricular conduction with and without AV nodal delay: two pathways to the
      bundle of His in the rabbit heart.
AB  - The electrophysiological properties of atrioventricular (AV) nodal dual pathways
      have traditionally been investigated with premature stimuli delivered with right
      atrial pacing. However, little is known about the functional characteristics of
      AV nodal inputs outside of this context. Superfused rabbit triangle of Koch
      preparations (n = 8) and Langendorff-perfused hearts (n = 10) were paced
      throughout the triangle of Koch and mapped electrically and optically for
      activation pattern, electrogram and optical action potential morphologies,
      stimulation thresholds, and stimulus-His (S-H) intervals. Optical mapping and
      changes in His electrogram morphology were used to confirm the activation
      pathway. Pacing stimuli >or=2 mm above the tricuspid valve caused fast-pathway
      activation of the AV node and His with a threshold of 2.4 +/- 1.6 mA. An area
      directly below the coronary sinus had high thresholds (8.6 +/- 1.4 mA) that also
      resulted in fast-pathway excitation (P < 0.001). S-H intervals (81 +/- 19 ms) for
      fast-pathway activation remained constant throughout the triangle of Koch,
      reflecting the AV delay. Stimuli applied <2 mm from the tricuspid valve resulted
      in slow pathway (SP) excitation or direct His excitation (4.4 +/- 2.2 mA
      threshold; P < 0.001 compared with fast pathway). For SP/His pacing, S-H
      intervals showed a strong dependence on the distance from the His electrode and
      were significantly lower than S-H intervals for fast-pathway activation. SP/His
      pacing also displayed characteristic changes in His electrogram morphology. In
      conclusion, optical maps and S-H intervals for SP/His activation suggest that AV
      conduction via SP bypasses the compact AV node via the lower nodal bundle, which
      may be utilized to achieve long-term ventricular synchronization.

PMID- 17496220
TI  - Effects of D-4F on vasodilation, oxidative stress, angiostatin, myocardial
      inflammation, and angiogenic potential in tight-skin mice.
AB  - Systemic sclerosis (scleroderma, SSc) is an autoimmune, connective tissue
      disorder that is characterized by impaired vascular function, increased oxidative
      stress, inflammation of internal organs, and impaired angiogenesis. Tight skin
      mice (Tsk(-/+)) have a defect in fibrillin-1, resulting in replication of many of
      the myocardial and vascular features seen in humans with SSc. D-4F is an
      apolipoprotein A-I (apoA-I) mimetic that improves vascular function in diverse
      diseases such as hypercholesterolemia, influenza, and sickle cell disease. Tsk(
      /+) mice were treated with either phosphate-buffered saline (PBS) or D-4F (1
      mg.kg(-1).day(-1) for 6-8 wk). Acetylcholine and flow-induced vasodilation were
      examined in facialis arteries. Proinflammatory HDL (p-HDL) in murine and human
      plasma samples was determined by the cell-free assay. Angiostatin levels in
      murine and human plasma samples were determined by Western blot analysis. Hearts
      were examined for changes in angiostatin and autoantibodies against oxidized
      phosphotidylcholine (ox-PC). Angiogenic potential in thin sections of murine
      hearts was assessed by an in vitro vascular endothelial growth factor (VEGF)
      induced endothelial cell (EC) tube formation assay. D-4F improved endothelium-,
      endothelial nitric oxide synthase-dependent, and flow-mediated vasodilation in
      Tsk(-/+) mice. Tsk(-/+) mice had higher plasma p-HDL and angiostatin levels than
      C57BL/6 mice, as did SSc patients compared with healthy control subjects. Tsk(
      /+) mice also had higher triglycerides than C57BL/6 mice. D-4F reduced p-HDL,
      angiostatin, and triglycerides in the plasma of Tsk(-/+) mice. Tsk(-/+) hearts
      contained notably higher levels of angiostatin and autoantibodies against ox-PC
      than those of control hearts. D-4F ablated angiostatin in Tsk(-/+) hearts and
      reduced autoantibodies against ox-PC by >50% when compared with hearts from
      untreated Tsk(-/+) mice. Angiogenic potential in Tsk(-/+) hearts was increased
      only when the Tsk(-/+) mice were treated with D-4F (1 mg.kg(-1).day(-1), 6-8 wk),
      and cultured sections of hearts from the D-4F-treated Tsk(-/+) mice were
      incubated with D-4F (10 microg/ml, 5-7 days). Failure to treat the thin sections
      of hearts and Tsk(-/+) mice with D-4F resulted in loss of VEGF-induced EC tube
      formation. D-4F improves vascular function, decreases myocardial inflammation,
      and restores angiogenic potential in the hearts of Tsk(-/+) mice. As SSc patients
      have increased plasma p-HDL and angiostatin levels similar to the Tsk(-/+) mice,
      D-4F may be effective at treating vascular complications in patients with SSc.

PMID- 17496221
TI  - Summary of the Northeast Regional Life Science Core Directors (NERLSCD) 2006
      meeting.

PMID- 17496222
TI  - Optimizing Phytoplasma DNA purification for genome analysis.
AB  - Genome analysis of uncultivable plant pathogenic phytoplasmas is hindered by the
      difficulty in obtaining sufficient quantities of phytoplasma enriched DNA. We
      investigated a combination of conventional enrichment techniques such as cesium
      chloride (CsCl) buoyant gradient centrifugation, and new methods such as rolling
      circle amplification (RCA), suppression subtractive hybridization (SSH), and
      mirror orientation selection (MOS) to obtain DNA with a high phytoplasma:host
      ratio as the major first step in genome analysis of Candidatus Phytoplasma
      australiense. The phytoplasma:host ratio was calculated for five different
      plasmid libraries. Based on sequence data, 90% of clones from CsCl DNA enrichment
      contained chromosomal phytoplasma DNA, compared to 60% from RCA CsCl DNA and 20%
      from SSH subtracted libraries. Based on an analysis of representative libraries,
      none contained plant DNA. A high percentage of clones (80-100%) from SSH
      libraries contained extrachromosomal DNA (eDNA), and we speculate that eDNA in
      the original DNA preparation was amplified in subsequent SSH manipulations.
      Despite the availability of new techniques for nucleic acid amplification, we
      found that conventional CsCl gradient centrifugation was the best enrichment
      method for obtaining chromosomal phytoplasma DNA with low host DNA content.

PMID- 17496223
TI  - DNA sequencing research group: 2006 general survey of DNA sequencing facilities.
AB  - Over the past few years, technological advances in automated DNA sequencing have
      had a profound effect on the nature of DNA sequencing laboratories. To
      characterize the changes occurring within DNA sequencing facilities, the DNA
      Sequencing Research Group conducted three previous studies, in 1998, 2000, and
      2003. A new general survey has been designed and conducted by the DSRG to capture
      the current status of DNA sequencing facilities in all sectors. Included were
      questions regarding facility administration, pricing, instrumentation,
      technology, protocols, and operation. The results of the survey are presented
      here, accompanied by comparisons to the previous surveys. These comparisons
      formed a basis for the discussion of trends within the facilities in response to
      the dynamics of a changing technology.

PMID- 17496224
TI  - Comparison of doxycycline delivery methods for Tet-inducible gene expression in a
      subcutaneous xenograft model.
AB  - Doxycycline (Dox) controlled Tet systems provide a powerful and commonly used
      method for functional studies on the consequences of gene
      overexpression/downregulation. However, whereas Dox delivery in tissue culture in
      vitro is relatively simple, the situation in vivo is more complex. Several
      methods of Dox delivery in vivo have been described-e.g., in drinking water
      containing alcohol, in drinking water containing various concentrations of
      sucrose, and in feed. Unfortunately there are no reports directly comparing the
      advantages and disadvantages of these diverse methods, and there is no generally
      accepted standard. We therefore compared four non-invasive methods of Dox
      delivery in vivo-in drinking water, by gavage, as a jelly, and in standard feed.
      To assess the delivery of Dox by these methods, we used a subcutaneous xenograft
      model based on colorectal carcinoma cells engineered for Dox-inducible expression
      of an activated mutant of c-Src and the luciferase reporter gene. Our results
      indicate that feed represents the most favorable method of Dox administration.

PMID- 17496225
TI  - ABRF-PRG04: differentiation of protein isoforms.
AB  - Accurate protein identification sometimes requires careful discrimination between
      closely related protein isoforms that may differ by as little as a single amino
      acid substitution or post-translational modification. The ABRF Proteomics
      Research Group sent a mixture of three picomoles each of three closely related
      proteins to laboratories who requested it in the form of intact proteins, and
      participating laboratories were asked to identify the proteins and report their
      results. The primary goal of the ABRF-PRG04 Study was to give participating
      laboratories a chance to evaluate their capabilities and practices with regards
      to sample fractionation (1D- or 2D-PAGE, HPLC, or none), protein digestion
      methods (in-solution, in-gel, enzyme choice), and approaches to protein
      identification (instrumentation, use of software, and/or manual techniques to
      facilitate interpretation), as well as determination of amino acid or post
      translational modifications. Of the 42 laboratories that responded, 8 (19%)
      correctly identified all three isoforms and N-terminal acetylation of each, 16
      (38%) labs correctly identified two isoforms, 9 (21%) correctly identified two
      isoforms but also made at least one incorrect identification, and 9 (21%) made no
      correct protein identifications. All but one lab used mass spectrometry, and data
      submitted enabled a comparison of strategies and methods used.

PMID- 17496226
TI  - The use of exhaled nitric oxide to guide asthma management: a randomized
      controlled trial.
AB  - RATIONALE: Current asthma guidelines recommend adjusting antiinflammatory
      treatment on the basis of the results of lung function tests and symptom
      assessment, neither of which are closely associated with airway inflammation.
      OBJECTIVES: We tested the hypothesis that titrating corticosteroid dose using the
      concentration of exhaled nitric oxide in exhaled breath (Fe(NO)) results in fewer
      asthma exacerbations and more efficient use of corticosteroids, when compared
      with traditional management. METHODS: One hundred eighteen participants with a
      primary care diagnosis of asthma were randomized to a single-blind trial of
      corticosteroid therapy based on either Fe(NO) measurements (n = 58) or British
      Thoracic Society guidelines (n = 60). Participants were assessed monthly for 4
      months and then every 2 months for a further 8 months. The primary outcome was
      the number of severe asthma exacerbations. Analyses were by intention to treat.
      MEASUREMENTS AND MAIN RESULTS: The estimated mean (SD) exacerbation frequency was
      0.33 per patient per year (0.69) in the Fe(NO) group and 0.42 (0.79) in the
      control group (mean difference, -21%; 95% confidence interval [CI], -57 to 43%; p
      = 0.43). Overall the Fe(NO) group used 11% more inhaled corticosteroid (95% CI, 
      17 to 42%; p = 0.40), although the final daily dose of inhaled corticosteroid was
      lower in the Fe(NO) group (557 vs. 895 microg; mean difference, 338 microg; 95%
      CI, -640 to -37; p = 0.028). CONCLUSIONS: An asthma treatment strategy based on
      the measurement of exhaled nitric oxide did not result in a large reduction in
      asthma exacerbations or in the total amount of inhaled corticosteroid therapy
      used over 12 mo, when compared with current asthma guidelines. Clinical trial
      registered with www.controlled-trials.com (ISRCTN08067387).

PMID- 17496228
TI  - Engraftment of bone marrow progenitor cells in a rat model of asbestos-induced
      pulmonary fibrosis.
AB  - RATIONALE: Bone marrow-derived cells have been shown to engraft during lung
      fibrosis. However, it is not known if similar cells engraft consequent to
      inhalation of asbestos fibers that cause pulmonary fibrosis, or if the cells
      proliferate and differentiate at sites of injury. OBJECTIVES: We examined whether
      bone marrow-derived cells participate in the pulmonary fibrosis that is produced
      by exposure to chrysotile asbestos fibers. METHODS: Adult female rats were
      lethally irradiated and rescued by bone marrow transplant from male transgenic
      rats ubiquitously expressing green fluorescent protein (GFP). Three weeks later,
      the rats were exposed to an asbestos aerosol for 5 hours on three consecutive
      days. Controls were bone marrow-transplanted but not exposed to asbestos.
      MEASUREMENTS AND MAIN RESULTS: One day and 2.5 weeks after exposure, significant
      numbers of GFP-labeled male cells had preferentially migrated to the bronchiolar
      alveolar duct bifurcations, the specific anatomic site at which asbestos produces
      the initial fibrogenic lesions. GFP-positive cells were present at the lesions as
      monocytes and macrophages, fibroblasts, and myofibroblasts or smooth muscle
      cells. Staining with antibodies to PCNA demonstrated that some of the engrafted
      cells were proliferating in the lesions and along the bronchioles. Negative
      results for TUNEL at the lesions confirmed that both PCNA-positive endogenous
      pulmonary cells and bone marrow-derived cells were proliferating rather than
      undergoing apoptosis, necrosis, or DNA repair. CONCLUSIONS: Bone marrow-derived
      cells migrated into developing fibrogenic lesions, differentiated into multiple
      cell types, and persisted for at least 2.5 weeks after the animals were exposed
      to aerosolized chrysotile asbestos fibers.

PMID- 17496229
TI  - Carbon monoxide poisoning: risk factors for cognitive sequelae and the role of
      hyperbaric oxygen.
AB  - RATIONALE: Carbon monoxide poisoning is common and causes cognitive sequelae.
      Hyperbaric oxygen (HBO(2)) reduces cognitive sequelae incidence, but which
      patients may benefit from HBO(2) is unclear. OBJECTIVES: Risk factor
      determination for 6-wk cognitive sequelae from CO poisoning and risk modification
      with HBO(2). METHODS: Patients were from a randomized controlled trial, enrolling
      acutely CO-poisoned patients more than 15 years of age. Patients eligible but not
      enrolled in the randomized trial, and not receiving HBO(2), were followed during
      the study interval. In patients not receiving HBO(2), we performed univariate
      analyses including risk factors identified by randomized trial subgroup analyses.
      A multivariable analysis was performed using univariate results with and without
      HBO(2). MEASUREMENTS AND MAIN RESULTS: In 163 patients not receiving HBO(2), 68
      (42%) manifested sequelae. Risk factors for sequelae from subgroup analyses were
      loss of consciousness, age of 36 years or more, and carboxyhemoglobin levels
      greater than or equal to 25%. By univariate analyses, risks for sequelae were age
      of 36 years or more (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.3-4.9;
      P = 0.005), and exposure intervals greater than or equal to 24 hours (OR, 2.4;
      95% CI, 1.2-4.8; P = 0.019). Including 75 patients receiving HBO(2), cognitive
      sequelae was reduced in patients age of 36 years or more (OR, 0.3; 95% CI, 0.2
      0.6; P < 0.001). Exposure intervals greater than or equal to 24 hours are an
      independent risk factor for sequelae (OR, 2.0; 95% CI, 1.0-3.8; P = 0.046).
      CONCLUSIONS: HBO(2) oxygen is indicated for patients with acute CO poisoning who
      are 36 years or older or have exposure intervals greater than or equal to 24
      hours. In addition, subgroup analyses support that patients with loss of
      consciousness or higher carboxyhemoglobin levels warrant HBO(2).

PMID- 17496230
TI  - Characteristics and trends of published emergency medicine research.
AB  - OBJECTIVES: Despite its importance in improving patient care, the state of
      published emergency medicine (EM) research is poorly understood. The countries of
      origin, methodological characteristics, sources of funding, and ongoing trends in
      this research are unknown. Knowledge of these characteristics has important
      policy, research, and clinical implications for academic EM. METHODS: The
      National Library of Medicine's PubMed database was searched for all articles
      published from 1996 to 2005 that originated from EM departments. The date and
      journal of publication, country of origin, study methodology, and, in the case of
      U.S. articles, acknowledgment of National Institutes of Health (NIH) grant
      support were noted. Journal impact factors of the publishing journal were
      assigned to each article. The aggregated data were then analyzed for country,
      journal of origin, and trend. RESULTS: Of the 14,605 articles originating from EM
      departments, the United States published 8,550 (58.54%), followed by the United
      Kingdom with 1,222 (8.37%) and Japan with 663 (4.54%). Significant publication
      growth was detected worldwide (116.6 articles per year; 95% confidence interval =
      101.1 to 132.1; p < 0.0001) and in 17 of the top 20 EM research-producing
      countries. Among published U.S. studies, the NIH funded 388 (4.5%). Of all
      articles, 6,152 (41.8%) were published in dedicated EM journals. CONCLUSIONS:
      Emergency medicine research output is increasing worldwide. The United States is
      the largest producer of EM research, only a small fraction of which is supported
      by the NIH. The majority of research published by emergency researchers is
      published in non-EM journals.

PMID- 17496231
TI  - Human rhinovirus attenuates the type I interferon response by disrupting
      activation of interferon regulatory factor 3.

PMID- 17496232
TI  - Mitochondrial nitric oxide in the signaling of cell integrated responses.
AB  - Mitochondria are the specialized organelles for energy metabolism, but, as a
      typical example of system biology, they also activate a multiplicity of pathways
      that modulate cell proliferation and mitochondrial biogenesis or oppositely
      promote cell arrest and programmed cell death by a limited number of oxidative or
      nitrosative reactions. These reactions are influenced by matrix nitric oxide (NO)
      steady-state concentration, either from local production or by gas diffusion to
      mitochondria from the canonical sources. Likewise, in a range of approximately 30
      200 nM, NO turns mitochondrial O(2) utilization down by binding to cytochrome
      oxidase and elicits a burst of superoxide anion and hydrogen peroxide that
      diffuses outside mitochondria. Depending on NO levels and antioxidant defenses,
      more or less H(2)O(2) accumulates in cytosol and nucleus, and the resulting redox
      grading contributes to dual activation of proliferating and proapoptotic
      cascades, like ERK1/2 or p38 MAPK. Moreover, these sequential activating pathways
      participate in rat liver and brain development and in thyroid modulation of
      mitochondrial metabolism and contribute to hypothyroid phenotype through complex
      I nitration. On the contrary, lack of NO disrupts pathways like S-nitrosylation
      or H(2)O(2) production and likewise is a gateway to disease in amyotrophic
      lateral sclerosis with superoxide dismutase 1 mutations or to cancer
      proliferation.

PMID- 17496233
TI  - LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1
      (EDG2) in breast carcinoma cells.
AB  - Lysophosphatidic acid (LPA) acts via binding to specific G protein-coupled
      receptors and has been implicated in the biology of breast cancer. Here, we
      characterize LPA receptor expression patterns in common established breast cancer
      cell lines and their contribution to breast cancer cell motility. By measuring
      expression of the LPA receptors LPA1, LPA2, and LPA3 with real-time quantitative
      PCR, we show that the breast cancer cell lines tested can be clustered into three
      main groups: cells that predominantly express LPA1 (BT-549, Hs578T, MDA-MB-157,
      MDA-MB-231, and T47D), cells that predominantly express LPA2 (BT-20, MCF-7, MDA
      MB-453, and MDA-MB-468), and a third group that shows comparable expression level
      of these two receptors (MDA-MB-175 and MDA-MB-435). LPA3 expression was detected
      primarily in MDA-MB-157 cells. Using a Transwell chemotaxis assay to monitor dose
      response, we find that cells predominantly expressing LPA1 have a peak migration
      rate at 100 nM LPA that drops off dramatically at 1 microM LPA, whereas cells
      predominantly expressing LPA2 show the peak migration rate at 1 microM LPA, which
      remains high at 10 microM. Using BT-20 cells, LPA2-specific small interfering
      RNA, and C3 exotransferase, we demonstrate that LPA2 can mediate LPA-stimulated
      cell migration and activation of the small GTPase RhoA. Using LPA2 small
      interfering RNA, exogenous expression of LPA1, and treatment with Ki16425 LPA
      receptor antagonist in the BT-20 cells, we further find that LPA1 and LPA2
      cooperate to promote LPA-stimulated chemotaxis. In summary, our results suggest
      that the expression of both LPA1 and LPA2 may contribute to chemotaxis and may
      permit cells to respond optimally to a wider range of LPA concentrations, thus
      revealing a new aspect of LPA signaling.

PMID- 17496234
TI  - The actions of a novel potent islet beta-cell specific ATP-sensitive K+ channel
      opener can be modulated by syntaxin-1A acting on sulfonylurea receptor 1.
AB  - Islet beta-cell-specific ATP-sensitive K(+) (K(ATP)) channel openers thiadiazine
      dioxides induce islet rest to improve insulin secretion, but their molecular
      basis of action remains unclear. We reported that syntaxin-1A binds nucleotide
      binding folds of sulfonylurea receptor 1 (SUR1) in beta-cells to inhibit K(ATP)
      channels. As a strategy to elucidate the molecular mechanism of action of these
      K(ATP) channel openers, we explored the possibility that 6-chloro-3-(1
      methylcyclobutyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NNC55
      0462) might influence syntaxin-1A-SUR1 interactions or vice versa. Whole-cell and
      inside-out patch-clamp electrophysiology was used to examine the effects of
      glutathione S-transferase (GST)-syntaxin-1A dialysis or green fluorescence
      protein/syntaxin-1A cotransfection on NNC55-0462 actions. In vitro pull-down
      binding studies were used to examine NNC55-0462 influence on syntaxin-1A-SUR1
      interactions. Dialysis of GST-syntaxin-1A into the cell cytoplasm reduced both
      potency and efficacy of extracellularly perfused NNC55-0462 in a HEK cell line
      stably expressing Kir6.2/SUR1 (BA8 cells) and in rat islet beta-cells. Moreover,
      inside-out membrane patches excised from BA8 cells showed that both GST-syntaxin
      1A and its H3 domain inhibited K(ATP) channels previously activated by NNC55
      0462. This action on K(ATP) channels is isoform-specific to syntaxin-1A because
      syntaxin-2 was without effect. Furthermore, the parent compound diazoxide showed
      similar sensitivity to GST-syntaxin-1A inhibition. NNC55-0462, however, did not
      influence syntaxin-1A-SUR1 binding interaction. Our results demonstrated that
      syntaxin-1A interactions with SUR1 at its cytoplasmic domains can modulate the
      actions of the K(ATP) channel openers NNC55-0462 and diazoxide on K(ATP)
      channels. The reduced levels of islet syntaxin-1A in diabetes would thus be
      expected to exert a positive influence on the therapeutic effects of this class
      of K(ATP) channel openers.

PMID- 17496235
TI  - Transfusion of apoptotic beta-cells induces immune tolerance to beta-cell
      antigens and prevents type 1 diabetes in NOD mice.
AB  - In vivo induction of beta-cell apoptosis has been demonstrated to be effective in
      preventing type 1 diabetes in NOD mice. Based on the notion that steady-state
      cell apoptosis is associated with self-tolerance and the need for developing a
      more practical approach using apoptotic beta-cells to prevent type 1 diabetes,
      the current study was designed to investigate apoptotic beta-cells induced ex
      vivo in preventing type 1 diabetes. The NIT-1 cell line serves as a source of
      beta-cells. Apoptotic NIT-1 cells were prepared by ultraviolet B (UVB)
      irradiation. Three weekly transfusions of UVB-irradiated NIT-1 cells (1 x
      10(5)/mouse) or PBS were used to determine whether transfusions of UVB-irradiated
      NIT-1 cells induce immune tolerance to beta-cell antigens in vivo and prevent
      type 1 diabetes. The suppression of anti-beta-cell antibodies, polarization of T
      helper (Th) cells, and induction of regulatory T-cells by UVB-irradiated NIT-1
      cell treatment were investigated. The transfusions of apoptotic NIT-1 cells
      suppress anti-beta-cell antibody development and induce Th2 responses and
      interleukin-10-producing regulatory type 1 cells. Importantly, this treatment
      significantly delays and prevents the onset of diabetes when 10-week-old NOD mice
      are treated. Adoptive transfer of splenocytes from UVB-irradiated NIT-1 cell
      treated mice prevents diabetes caused by simultaneously injected diabetogenic
      splenocytes in NOD-Rag(-/-) mice. Moreover, the proliferation of adoptively
      transferred carboxyfluorescein diacetate succinimidyl ester-labeled beta-cell
      antigen-specific T-cell receptor-transgenic T-cells in UVB-irradiated NIT-1-cell
      treated mice is markedly suppressed. The transfusion of apoptotic beta-cells
      effectively protects against type 1 diabetes in NOD mice by inducing immune
      tolerance to beta-cell antigens. This approach has great potential for immune
      intervention for human type 1 diabetes.

PMID- 17496236
TI  - Effect of 2 years of testosterone replacement on insulin secretion, insulin
      action, glucose effectiveness, hepatic insulin clearance, and postprandial
      glucose turnover in elderly men.
AB  - OBJECTIVE: We sought to determine whether, and if so the mechanism by which,
      testosterone replacement improves carbohydrate tolerance. RESEARCH DESIGN AND
      METHODS: Fifty-five elderly men with relative testosterone deficiency ingested a
      labeled mixed meal and underwent a frequently sampled labeled intravenous glucose
      tolerance test before and after either placebo or treatment with testosterone
      patch (5 mg/day) for 2 years. RESULTS: Despite restoring bioavailable
      testosterone to values observed in young men, the change (24 months minus
      baseline values) in fasting and postprandial glucose, insulin, and C-peptide
      concentrations and meal appearance, glucose disposal, and endogenous glucose
      production were virtually identical to those observed after 2 years of placebo.
      The change over time in insulin and C-peptide concentrations post-intravenous
      glucose injection also did not differ. Furthermore, the change over time in
      insulin action and glucose effectiveness (measured with the unlabeled and labeled
      "oral" and "intravenous" minimal models), as well as insulin secretion and
      hepatic insulin clearance (measured with the C-peptide model), did not differ in
      the testosterone and placebo groups. CONCLUSIONS: We conclude that 2 years of
      treatment with testosterone in elderly men does not improve carbohydrate
      tolerance or alter insulin secretion, insulin action, glucose effectiveness,
      hepatic insulin clearance, or the pattern of postprandial glucose metabolism.
      Thus, testosterone deficiency is unlikely the cause of the age-associated
      deterioration in glucose tolerance commonly observed in elderly men.

PMID- 17496237
TI  - Diabetes epidemiology: guiding clinical and public health practice: the Kelly
      West Award Lecture, 2006.

PMID- 17496238
TI  - Single oral challenge by advanced glycation end products acutely impairs
      endothelial function in diabetic and nondiabetic subjects.
AB  - OBJECTIVE: The current study was designed to test the acute effects of dietary
      advanced glycation end products (AGEs) on endothelial function of diabetic and
      nondiabetic subjects. RESEARCH DESIGN AND METHODS: Flow-mediated dilation (FMD)
      of the brachial artery and serum levels of AGEs, plasminogen activator inhibitor
      1 (PAI-1), vascular cell adhesion molecule 1 (VCAM-1), and glucose were assessed
      before and after a single oral AGE challenge (approximately 1.8 x 10(6) AGE
      units) in 44 diabetic and 10 nondiabetic subjects. RESULTS: The diabetic patients
      had higher baseline levels of serum AGEs (P = 0.020), PAI-1 (NS), and VCAM-1 (P =
      0.033) and lower baseline values of FMD compared with nondiabetic subjects (P =
      0.032). Ninety minutes after a single oral AGE challenge, serum AGEs and PAI-1
      levels increased and FMD decreased significantly in both healthy subjects (AGEs:
      7.2 +/- 0.5 to 9.3 +/- 1 units/ml, P = 0.014; PAI-1: 5.4 +/- 0.4 to 6.8 +/- 0.4
      ng/ml, P = 0.007; and FMD: 9.9 +/- 0.7 to 7.4 +/- 0.9%, P = 0.019) and diabetic
      subjects (AGEs: 10.5 +/- 0.7 to 14.2 +/- 1 units/ml, P = 0.020; PAI-1: 6.5 +/- 1
      to 10 +/- 2 ng/ml, P = 0.030; and FMD: 5.4 +/- 0.4 to 4.0 +/- 0.3%, P = 0.032).
      Serum glucose and VCAM-1 levels remained unchanged. CONCLUSIONS: Significant
      increases in serum AGEs can occur together with altered clinical measures of
      endothelial function in diabetic and nondiabetic subjects after a single modest
      AGE-rich beverage. Thus, repeated or chronic exposure to high AGE diets could
      over time lead to and/or accelerate vascular disease.

PMID- 17496227
TI  - Effect of lung volume reduction surgery on resting pulmonary hemodynamics in
      severe emphysema.
AB  - RATIONALE: To determine the effect of medical treatment versus lung volume
      reduction surgery (LVRS) on pulmonary hemodynamics. METHODS: Three clinical
      centers of the National Emphysema Treatment Trial (NETT) screened patients for
      additional inclusion into a cardiovascular (CV) substudy. Demographics were
      determined, and lung function testing, six-minute-walk distance, and maximum
      cardiopulmonary exercise testing were done at baseline and 6 months after medical
      therapy or LVRS. CV substudy patients underwent right heart catheterization at
      rest prerandomization (baseline) and 6 months after treatment. MEASUREMENTS AND
      MAIN RESULTS: A total of 110 of the 163 patients evaluated for the CV substudy
      were randomized in NETT (53 were ineligible), 54 to medical treatment and 56 to
      LVRS. Fifty-five of these patients had both baseline and repeat right heart
      catheterization 6 months postrandomization. Baseline demographics and lung
      function data revealed CV substudy patients to be similar to the remaining 1,163
      randomized NETT patients in terms of age, sex, FEV(1), residual volume, diffusion
      capacity of carbon monoxide, Pa(O(2)), Pa(CO(2)), and six-minute-walk distance.
      CV substudy patients had moderate pulmonary hypertension at rest (Ppa, 24.8 +/-
      4.9 mm Hg); baseline hemodynamic measurements were similar across groups. Changes
      from baseline pressures to 6 months post-treatment were similar across treatment
      groups, except for a smaller change in pulmonary capillary wedge pressure at end
      expiration post-LVRS compared with medical treatment (-1.8 vs. 3.5 mm Hg, p =
      0.04). CONCLUSIONS: In comparison to medical therapy, LVRS was not associated
      with an increase in pulmonary artery pressures.

PMID- 17496239
TI  - Medicare cost effects of recent U.S. disability trends in the elderly: future
      implications.
AB  - OBJECTIVE: The authors examine how trends in disability prevalence and in
      inflation-adjusted per capita, per annum Medicare costs, 1982 to 1999 and 1989 to
      1999, affected total Medicare costs projected to 2004 and 2009. METHOD: To
      describe disability trends, the authors applied grade of membership analyses to
      27 measures of disability from the 1982 to 1999 National Long Term Care Surveys
      (NLTCS). This identified seven disability profiles for which individual scores
      were calculated. These were used to calculate sample weighted Medicare costs and
      cost trends. RESULTS: Significant declines (up to 19%) in Medicare costs were
      found in 2004 and 2009 assuming continuation of the 1982 to 1999 disability
      declines and Medicare cost trends. In addition to declines in disability
      prevalence, inflation-adjusted per capita, per annum Medicare costs declined for
      nondisabled persons aged 65 to 84. DISCUSSION: Preserving health in the growing
      nondisabled population did not require increased health care expenditures.

PMID- 17496240
TI  - Severity of concurrent visual and hearing impairment and mortality: the 1986-1994
      National Health Interview Survey.
AB  - PURPOSE: Visual impairment and, to a lesser extent, hearing impairment are
      independent predictors of reduced survival in selected studies of community
      residing adults. To date, the association of severity of concurrent impairment
      and mortality has not been examined. METHOD: The National Health Interview Survey
      is a continuous, multistage, area probability survey of the U.S. civilian
      noninstitutionalized population. Mortality linkage with the National Death Index
      of 116,796 adult participants from 1986 to 1994 with complete impairment data was
      performed through 1997. RESULTS: Findings indicate that moderate to severe
      concurrent hearing and visual impairment in women is associated with
      significantly increased risk of mortality. More modest mortality associations are
      evident for men and for adults with less severe impairments, irrespective of
      gender. DISCUSSION: Prevention of severe visual and hearing impairment should be
      a national public health priority, especially given the aging of the U.S.
      population.

PMID- 17496241
TI  - Complexity of primary lifetime occupation and cognition in advanced old age.
AB  - OBJECTIVE: The authors explored the association between complexity of primary
      lifetime occupation and cognition in older adulthood. METHOD: The study included
      386 participants from the Swedish Panel Study of Living Conditions of the Oldest
      Old, a nationally representative sample aged 77 years or older. The authors
      examined complexity of work with data, people, and things in relation to
      cognitive functioning, measured with a shortened version of Mini-Mental State
      Examination (MMSE) and cognitive impairment based on MMSE score cutoff. RESULTS:
      Complexity of work with data and people were associated with better MMSE scores,
      controlling for age, sex, childhood socioeconomic status, and education. The
      association between complexity of work with data and MMSE remained statistically
      significant when adult occupational status was substituted for education as a
      covariate. DISCUSSION: Complexity of primary lifetime occupation may be reflected
      in cognitive functioning even in advanced old age. This effect may be independent
      of education or occupational status.

PMID- 17496242
TI  - Chronic disease and lifestyle transitions: results from the Longitudinal Aging
      Study Amsterdam.
AB  - OBJECTIVE: This article addresses the association between course of chronic
      disease and lifestyle. METHOD: We examined differences in unhealthy lifestyles-
      smoking, excessive alcohol use, being sedentary--and transitions herein after 6
      years in prevalent and incident chronic disease categories--lung and
      cardiovascular disease, diabetes, and osteoarthritis and/or rheumatic arthritis-
      among 2,184 respondents aged 55 years and older from the Netherlands. We also
      examined if transitions in lifestyle co-occurred with changes in disease-related
      symptomatology. RESULTS: Proportions of respondents who smoked decreased over
      time, whereas proportions of respondents who were sedentary increased.
      Respondents with incident cardiovascular disease demonstrated more lifestyle
      transitions than respondents from other disease categories. Respondents
      demonstrating healthy lifestyle transitions did not differ from those persisting
      in unhealthy lifestyles in change in disease-related symptoms. DISCUSSION: Health
      promotion may benefit from these findings in a way that patient groups at risk
      for not initiating healthy lifestyles might be identified sooner.

PMID- 17496243
TI  - The mediating role of health perceptions in the relation between physical and
      mental health: a study of older residents in assisted living facilities.
AB  - OBJECTIVE: Responding to the increased need for research on older residents in
      assisted living facilities (ALFs), this study assessed the connections between
      physical and mental health among 150 older residents in ALF settings. METHOD: The
      major focus of the study was to explore whether individuals' subjective
      perceptions of their own health mediate the associations between health-related
      variables (chronic conditions and functional disability) and depressive symptoms.
      RESULTS: The analyses showed that the adverse effects of chronic conditions and
      functional disability on depressive symptoms were not only direct but also
      indirect through negative health perceptions. DISCUSSION: The findings that
      health perceptions serve as an intervening step between physical and mental
      health provide important implications for promotion of mental well-being among
      older residents in ALFs. In addition to disease/disability prevention and health
      promotion efforts, attention should be paid to ways to enhance older individuals'
      positive beliefs and attitudes toward their own health and to promote healthful
      behaviors.

PMID- 17496244
TI  - Symptoms, affects, and self-rated health: evidence for a subjective trajectory of
      health.
AB  - OBJECTIVE: Self-rated health (SRH) is known to predict mortality and other health
      outcomes better than objective ratings, suggesting that patients have important
      knowledge that physicians do not. The study assessed whether SRH reflects changes
      in internal states, specifically symptoms and affects. METHOD: In an event
      sampling study, 54 elders completed a SRH measure, positive and negative affect
      scale, a symptom checklist, and a pain scale every evening for 8 weeks. Using
      lagged (time series) hierarchical regression, the authors modeled associations of
      SRH with previous symptoms, moods, and changes in symptoms and mood. RESULTS: The
      SRH was highest when symptoms had decreased from the previous day and lowest when
      symptoms had increased, suggesting that SRH reflects a sense of change. Symptoms
      and affects contributed independently to SRH. Self-rated health was more
      sensitive to positive than negative affect and also sensitive to changes of
      positive but not negative affect. DISCUSSION: Patients may possess a subjective
      trajectory of health-an awareness of changes in symptoms and affect. This
      trajectory may constitute an important component of SRH and help to explain its
      ability to predict health outcomes.

PMID- 17496245
TI  - Factors that promote and prevent exercise engagement in older adults.
AB  - OBJECTIVE: This study aimed to (a) identify factors that motivate or prevent
      older Australians from exercising; (b) determine how these factors differ as a
      function of age, gender, and exercise level; and (c) examine how they relate to
      intentions to exercise in the future. METHOD: In all, 217 older adults (aged 63
      to 86) completed a questionnaire in their own home. Participants rated various
      motivators and barriers to exercise and indicated future intention to exercise.
      RESULTS: Health concerns were the strongest motivators to exercise, whereas
      physical ailments were the most common barrier to exercise. Older Australians
      were fairly motivated to exercise and experienced few barriers to exercise. Age,
      gender, and exercise level differentiated between reported motivators and
      barriers, which in turn were associated with future intentions to exercise.
      DISCUSSION: Reasons that promote and prevent exercise engagement are quite varied
      and depend on personal factors. Exercise intervention programs for older adults
      should incorporate these factors.

PMID- 17496246
TI  - Adult children and their parents' expectations of future elder care needs.
AB  - OBJECTIVE: Lifestyle changes and medical advances warrant an investigation into
      perceptions of elder care needs held by today's adult children (AC) and their
      parents. METHOD: Surveys were distributed to 200 AC. Eighty AC and 102 of their
      parents responded. RESULTS: Paired sample t tests revealed that AC (M = 10.61, SD
      = 4.5) and parents (M = 10.4, SD = 4.60) did not differ in their own expectations
      of future care needs. However, ACs' expectations of their parents' needs (M =
      15.82, SD = 5.77) were significantly higher than both self-expectations. In
      addition, among six caregiving tasks minimal but significant differences were
      found in expected receipt of assistance. DISCUSSION: Consistent with Weinstein's
      (1980) theory of unrealistic optimism, results demonstrated the tendency for AC
      and parents to underestimate their own future care needs. Such underestimation
      may in turn, lead to inadequate planning for future care needs.

PMID- 17496247
TI  - Use of selection, optimization, and compensation strategies in health self
      regulation: interplay with resources and successful development.
AB  - PURPOSE: This study investigated the interplay of exercise strategy use (i.e.,
      strategies of selection, optimization, and compensation) and perceived loss of
      exercise resources in individuals prescribed to engage in physical exercise.
      METHOD: Specifically, 368 individuals (18 to 80 years) were assessed during
      orthopedic rehabilitation and 6 and 12 months thereafter. Exercise, orthopedic
      outcome, and subjective well-being served as indicators of successful
      development. RESULTS: There was no evidence for an interaction of age and
      strategy use. There was also no support for an interaction between resource loss
      and strategy use but rather for a mediating role of strategy use between resource
      loss and exercise. The effect of strategy use on orthopedic outcome and
      subjective well-being was mediated by exercise. DISCUSSION: Strategy use seems to
      be beneficial for exercise regardless of age. In addition, strategy use seems to
      enhance resources and is not only associated with exercise but also with
      orthopedic outcome and subjective well-being.

PMID- 17496248
TI  - The effectiveness of interventions to increase advance directive completion
      rates.
AB  - OBJECTIVE: Despite federal and state laws governing advance directives (ADs),
      interventions to increase rates of legally completed ADs have not produced
      significant results. This study synthesizes the state of the science regarding
      effectiveness of interventions to increase AD completion rates. METHODS:
      Garrard's method for conducting a systematic literature review was followed. In
      all, 25 studies meeting inclusion criteria were reviewed. Interventions fell into
      two types: (a) didactic-information distributed through an educational program or
      clinical encounter or by a mailing and (b) interactive-person-to-person
      interaction where participants had the opportunity to ask questions and/or
      receive assistance completing the forms. RESULTS: Postintervention rates of AD
      completion were: didactic = no change to 34% increase; interactive = 23% to 71%
      increase. DISCUSSION: Education without the ability to ask questions does not
      significantly increase the AD completion rate. Didactic interventions did not
      usually increase completion rates higher than the predicted average rate for the
      general population.

PMID- 17496249
TI  - Using religious services to improve health: findings from a sample of middle-aged
      and older adults with multiple sclerosis.
AB  - PURPOSE: The purpose of this study is to examine the use of religious services to
      improve health among middle-aged and older adults with multiple sclerosis (MS).
      METHOD: Data from the study "Aging With MS: Unmet Needs in the Great Lakes
      Region" were used to investigate religious service use among 1,275 adults with
      MS. RESULTS: The findings indicate that nearly two thirds of the sample currently
      use religious services to improve their health or well-being. Individuals whose
      MS is stable and those who have had the disease longer are significantly more
      likely to use religious services to improve their health. CONCLUSIONS: Religious
      organizations should continue providing out-reach and increasing accessibility
      for individuals with disabling conditions. In addition, health care professionals
      should be aware of the importance of religious services to individuals with MS
      and do their part to facilitate participation for those who desire it.

PMID- 17496250
TI  - The in vivo phosphorylation and glycosylation of human insulin-like growth factor
      binding protein-5.
AB  - Mass spectrometry is often used to determine post-translational modifications by
      analysis of tryptic digests of proteins. Here we demonstrate that the analysis of
      tryptic peptides together with analysis of the full-length protein provided
      optimal characterization of insulin-like growth factor-binding protein-5 (IGFBP
      5) phosphorylation and glycosylation. IGFBP-5 binds insulin-like growth factors
      with high affinity and has important roles in cell survival, differentiation, and
      apoptosis. Until now, the primary structure of IGFBP-5 has been incompletely
      defined. We analyzed human IGFBP-5 from T47D cells by mass spectrometry to
      determine all of the in vivo post-translational modifications. In full-length
      IGFBP-5, 31% of the protein was unmodified, 37% was monophosphorylated, and 4%
      was diphosphorylated with no other modification. The remaining 27% was
      glycosylated, more than half of which was also monophosphorylated. The major
      phosphorylation site was Ser(96) in the central domain, and a minor
      phosphorylation site was Ser(248) near the C terminus. Neither site was
      phosphorylated in vitro by casein kinase 2, ruling it out as the in vivo kinase.
      An in vivo phosphorylation site was also found in IGFBP-2 at an analogous
      position, Ser(106). IGFBP-5 was heterogeneously O-glycosylated mainly by
      sialylated core 1 type glycans. The most abundant structure contained N
      acetylhexosamine, hexose, and two N-acetylneuraminic acid carbohydrates. A small
      amount of sialylated core 2 type glycan was also present. Phosphorylation and O
      glycosylation both affected IGFBP-5 binding to heparin but not insulin-like
      growth factor binding or ternary complex formation with the acid-labile subunit.
      The results reveal the first description of the in vivo phosphorylation of IGFBP
      5 and its glycan composition.

PMID- 17496251
TI  - Social inequalities in health among the elderly: a challenge for public health
      research.

PMID- 17496252
TI  - The predictability of research in chronic illness.

PMID- 17496253
TI  - Local leadership in public health: the role of the medical officer of health in
      Britain, 1872-1974.
AB  - The recent policy focus in British public health on the importance of local
      action invites consideration of historical precedent. The role and achievements
      of the medical officer of health (MOH), the local government official charged
      with public health responsibilities, is discussed. The gradual accretion of
      duties is traced in the first section: the mid-Victorian concern with urban
      sanitation; the preventive strategies adopted after the bacteriological
      revolution; the extension of personal health services in the early 20th century;
      and the more diminished role under the National Health Service (NHS), when
      infectious diseases retreated. The historical verdicts passed on the MOsH are
      reviewed in the second section. The leading role of the MOsH in the late 19th
      century mortality decline has been reasserted, and although there is some
      justification in the argument that in the 20th century public health lost its
      focus, it is important to recall that the extension of personal health services
      under MOH direction signified a major extension of access to care. Similarly, the
      charge that MOsH did not redefine their role in the period before their final
      demise in 1974 is not entirely justified. The emphasis of the NHS on curative
      rather than preventive medicine, and the economic constraints on local authority
      health service expansion limited their room for manoeuvre. The history of local
      leadership in public health may offer some enduring lessons. These include the
      importance of monitoring local population health, acting as a public interface
      between medicine and the community, facilitating joined-up working and
      confronting vested interests.

PMID- 17496254
TI  - A typology of actions to tackle social inequalities in health.

PMID- 17496255
TI  - Childhood adversities as a predictor of disability retirement.
AB  - BACKGROUND: There is a large body of research on adulthood risk factors for
      retirement due to disability, but studies on the effect of adverse childhood
      experiences are scarce. AIM: To examine whether adverse childhood experiences
      predict disability retirement. METHODS: Data were derived from the Health and
      Social Support Study. The information was gathered from postal surveys in 1998
      (baseline) and in 2003 (follow-up questionnaire). The analysed data consisted of
      8817 non-retired respondents aged 40-54 years (5149 women, 3668 men). Negative
      childhood experiences, such as financial difficulties, serious conflicts and
      alcohol-related problems, were assessed at baseline and disability retirement at
      follow-up. RESULTS: The risk of disability retirement increased in a dose
      response manner with increasing number of childhood adversities. Respondents who
      had experienced multiple childhood adversities had a 3.46-fold increased risk
      (95% CI 2.09 to 5.71) of disability retirement compared with those who reported
      no such adversities. Low socioeconomic status, depression (Beck Depression
      Inventory-21), use of drugs for somatic diseases as well as health-related risk
      behaviour, such as smoking, heavy alcohol consumption and obesity, were also
      predictors of disability retirement. After simultaneous adjustments for all these
      risk factors, the association between childhood adversities and the risk of
      disability retirement attenuated, but remained significant (OR 1.90, 95% CI 1.07
      to 3.37). CONCLUSIONS: Information on childhood conditions may increase our
      understanding of the determinants of early retirement, especially due to mental
      disorders. Childhood adversities should be taken into account when considering
      determinants of disability retirement and identifying groups at risk.

PMID- 17496256
TI  - School culture as an influencing factor on youth substance use.
AB  - OBJECTIVE: To determine whether value-added education is associated with lower
      risk of substance use among adolescents: early initiation of alcohol use (regular
      monthly alcohol consumption in grade 7), heavy alcohol use (>10 units per week)
      and regular illicit drug use. DESIGN: Cross-sectional self-reported survey of
      alcohol and drug use. Analysis used two-level logistic modelling to relate
      schools providing value-added education with pupils' substance use. The value
      added education measure was derived from educational and parenting theories
      proposing that schools providing appropriate support and control enhance pupil
      functioning. It was operationalised by comparing observed and expected
      examination success and truancy rates among schools. Expected examination success
      and truancy rates were based on schools' sociodemographic profiles. PARTICIPANTS:
      Data were collected across 15 West Midlands English school districts and included
      25,789 pupils in grades 7, 9 and 11 from 166 UK secondary schools. RESULTS: Value
      added education was associated with reduced risk of early alcohol initiation (OR
      (95% CI) 0.87 (0.78 to 0.95)) heavy alcohol consumption (OR 0.91 (0.85 to 0.96))
      and illicit drug use (OR 0.90 (0.82 to 0.98)) after adjusting for gender, grade,
      ethnicity, housing tenure, eligibility for free school meal, drinking with
      parents and neighbourhood deprivation. CONCLUSIONS: The prevalence of substance
      use in school is influenced by the school culture. Understanding the mechanism
      through which the school can add value to the educational experience of pupils
      may lead to effective prevention programmes.

PMID- 17496257
TI  - Socioeconomic and food-related physical characteristics of the neighbourhood
      environment are associated with body mass index.
AB  - OBJECTIVE: To determine whether socioeconomic and food-related physical
      characteristics of the neighbourhood are associated with body mass index (BMI;
      kg/m(2)) independently of individual-level sociodemographic and behavioural
      characteristics. DESIGN AND METHODS: Observational study using (1) individual
      level data previously gathered in five cross-sectional surveys conducted by the
      Stanford Heart Disease Prevention Program between 1979 and 1990 and (2)
      neighbourhood-level data from (a) the census to describe socioeconomic
      characteristics and (b) data obtained from government and commercial sources to
      describe exposure to different types of retail food stores as measured by store
      proximity, and count of stores per square mile. Data were analysed using
      multilevel modelling procedures. The setting was 82 neighbourhoods in
      agricultural regions of California. PARTICIPANTS: 7595 adults, aged 25-74 years.
      RESULTS: After adjusting for age, gender, ethnicity, individual-level
      socioeconomic status, smoking, physical activity and nutrition knowledge, it was
      found that (1) adults who lived in low socioeconomic neighbourhoods had a higher
      mean BMI than adults who lived in high socioeconomic neighbourhoods; (2) higher
      neighbourhood density of small grocery stores was associated with higher BMI
      among women; and (3) closer proximity to chain supermarkets was associated with
      higher BMI among women. CONCLUSION: Living in low socioeconomic neighbourhoods,
      and in environments where healthy food is not readily available, is found to be
      associated with increased obesity risk. Unlike other studies which examined
      populations in other parts of the US, a positive association between living close
      to supermarkets and reduced obesity risk was not found in this study. A better
      understanding of the mechanisms by which neighbourhood physical characteristics
      influence obesity risk is needed.

PMID- 17496258
TI  - Change in the total and independent effects of education and occupational social
      class on mortality: analyses of all Finnish men and women in the period 1971
      2000.
AB  - OBJECTIVES: To estimate changes in the total and independent effects of education
      and occupational social class on mortality over 30 years, and to assess the
      causes of changes in the independent effects. METHODS: Census records linked with
      death records for 1971-2000 for all Finns aged 30-59 years were studied. The
      total and independent effects of education and social class on mortality were
      calculated from relative risks in nested Poisson regression models. RESULTS:
      Among men and women, the model shows that the total effects of education, and
      particularly occupational social class on mortality, have increased over time.
      Among 40-59-year-old people, the effects of education are currently less
      independent of social class than in the 1970s, but among younger Finns the
      independent effects have remained stable. The effects of social class on
      mortality that are independent of education have grown among people of older
      ages, particularly among men. CONCLUSIONS: Changes in the independent effects of
      socioeconomic measures on mortality are determined by changes in their
      associations with mortality, and distributional changes that affect the strength
      of the associations between these measures. Distributional changes are driven by
      changes in educational systems and labour markets, and are of major importance
      for the understanding of socioeconomic inequalities in mortality.

PMID- 17496259
TI  - Symptomatology attributable to psychological exposure to a chemical incident: a
      natural experiment.
AB  - BACKGROUND: Exposure to a complex emergency has a substantial psychological
      component, which is rarely assessed. This study compares the health impact of
      physically and psychologically mediated exposure to a complex emergency. SETTING:
      The Sea Empress oil tanker spill. DESIGN: A cross-sectional analysis of self
      report questionnaire responses collected from inhabitants of 6 different coastal
      towns-4 of them physically exposed to the oil spill, 2 unexposed-was undertaken.
      The towns were known to be psychologically homogeneous before the incident.
      Perceived risk was used as a measure of psychological exposure. Anxiety,
      depression and symptom reporting were used as measures of health impact.
      PARTICIPANTS: 1089 (69%) men and women aged 18-65 years responded. MAIN RESULTS:
      Perceived risk was associated with raised anxiety and non-toxicologically related
      symptom reporting, whereas physical exposure to oil was only associated with
      toxicologically related symptom reporting. The impact of raised perceived risk on
      the population was greater than that of physical oil exposure, involving more
      persons over a wider area. CONCLUSIONS: Psychological exposure was shown to be
      quantifiable, and to be a substantially more sensitive measure of health impact
      than physical exposure in relation to psychological outcomes. This type of
      analysis has important implications for emergency response planning, and for the
      interpretation of a complex emergency by the general public.

PMID- 17496260
TI  - Unfairness and health: evidence from the Whitehall II Study.
AB  - OBJECTIVE: To examine the effects of unfairness on incident coronary events and
      health functioning. DESIGN: Prospective cohort study. Unfairness,
      sociodemographics, established coronary risk factors (high serum cholesterol,
      hypertension, obesity, exercise, smoking and alcohol consumption) and other
      psychosocial work characteristics (job strain, effort-reward imbalance and
      organisational justice) were measured at baseline. Associations between
      unfairness and incident coronary events and health functioning were determined
      over an average follow-up of 10.9 years. PARTICIPANTS: 5726 men and 2572 women
      from 20 civil service departments in London (the Whitehall II Study). MAIN
      OUTCOME MEASURES: Incident fatal coronary heart disease, non-fatal myocardial
      infarction and angina (528 events) and health functioning. RESULTS: Low
      employment grade is strongly associated with unfairness. Participants reporting
      higher levels of unfairness are more likely to experience an incident coronary
      event (HR 1.55, 95% CI 1.11 to 2.17), after adjustment for age, gender,
      employment grade, established coronary risk factors and other work-related
      psychosocial characteristics. Unfairness is also associated with poor physical
      (OR 1.46, 95% CI 1.20 to 1.77) and mental (OR 1.54, 95% CI 1.19 to 1.99)
      functioning at follow-up, controlling for all other factors and health
      functioning at baseline. CONCLUSIONS: Unfairness is an independent predictor of
      increased coronary events and impaired health functioning. Further research is
      needed to disentangle the effects of unfairness from other psychosocial
      constructs and to investigate the societal, relational and biological mechanisms
      that may underlie its associations with health and heart disease.

PMID- 17496261
TI  - Evaluation of the quality of cause of death statistics in rural China using
      verbal autopsies.
AB  - BACKGROUND: Death registration systems in rural China are in a developmental
      stage. The Disease Surveillance Points (DSP) system provides the only nationally
      representative information on causes of death. In this system, there are no
      standard procedures or instruments for ascertaining causes of death; hence
      available statistics require careful evaluation before use. AIM: To assess the
      reliability of data from the DSP. METHODS: 14 DSP sites were selected through
      stratified sampling, enrolling 2482 deaths registered during June-November 2002.
      Defined verbal autopsy (VA) procedures were used to derive underlying causes of
      death. kappa Measures of agreement between VA and registered diagnoses were
      computed. VA diagnoses were used as references to compute sensitivity and
      positive predictive values. Finally, patterns of cause-specific discordance
      between the two data sources were studied. RESULTS: kappa Scores indicate only
      moderate agreement for chronic obstructive pulmonary disease (COPD) and ischaemic
      heart disease (IHD). The results also suggest that COPD is undercounted in
      registration data. A significant degree of cross attribution of cause was found
      between the two data sources. Overall, the VA was successful in limiting deaths
      with ill-defined causes to <10%. CONCLUSIONS: Diagnoses based on structured
      symptom questionnaires in the VA approach seem plausible and reliable as compared
      with lay-reported diagnoses in registration data. Concerns with attribution of
      cause of death due to COPD, IHD and tuberculosis in registration data suggest
      caution in their use for research and health programme purposes. The VA methods
      tested in this study offer promise for implementation in the routine registration
      system.

PMID- 17496262
TI  - Neighbourhood environment and the incidence of depressive symptoms among middle
      aged African Americans.
AB  - AIM: To investigate the association between attributes of subject location and
      incidence of clinically relevant levels of depressive symptoms (CRLDS), and to
      investigate whether an association remained after adjusting for individual-level
      factors using data from the population-based African American Health Study.
      METHODS: An 11-item depression scale (Center for Epidemiologic Studies Depression
      scale) was obtained at baseline and 3 years later through in-home evaluations.
      Census tract and block group deprivation indices were obtained from the 2000
      census. The external appearance of the block where the subject lived was rated
      during sample enumeration, and the interior and exterior of the subject's
      dwelling were observed during the initial in-home interview. RESULTS: Of 998
      subjects at baseline, 21.1% had CRLDS. Although 12.7% of the 672 people without
      CRLDS at baseline developed them by the 3-year follow-up, univariate and
      propensity-adjusted analyses revealed no association between the subject's
      location and the incidence of CRLDS. Sensitivity analyses confirmed the
      robustness of the findings. CONCLUSION: Despite other studies showing independent
      effects of neighbourhood characteristics on the prevalence of CRLDS, attributes
      of subject location are not independent contributors to the incidence of CRLDS in
      middle-aged urban African Americans.

PMID- 17496263
TI  - The long shadow of work - does time since labour market exit affect the
      association between socioeconomic position and health in a post-working
      population.
AB  - OBJECTIVE: To test the effect of time since labour market exit (LME) on
      associations between socioeconomic position (SEP) and self-rated health. METHODS:
      Retirees from the English Longitudinal Study of Ageing (ELSA) were divided into
      three groups on the basis of the length of time since LME. Seven different
      indicators of SEP were identified: socioeconomic class, income, wealth,
      education, tenure, area deprivation and subjective social status. Unadjusted and
      mutually adjusted logistic regression analyses were performed with poor self
      rated health as the outcome. The sample consisted of 2617 men (mean (SD) age
      71.69 (7.04) years) and 2619 women (71.29 (8.26) years). RESULTS: In the
      unadjusted analyses, patterns of association between SEP measures and health were
      similar for men and women. Most SEP measures were associated with poor health,
      although the effects were attenuated by time since LME. In the mutually adjusted
      analyses, wealth was found to have a strong independent effect on health among
      men, especially in those groups that left the labour market < or = 20 years
      ago,while for women subjective social status seemed to have the most important
      effect on health after LME. CONCLUSIONS: Time since LME is an important factor to
      consider when studying health inequalities in a post-working population. The
      effect of time since LME varies according to gender and the measures of SEP used.
      Further work in this area should take account of age, period and cohort effects
      using multiple measures of SEP and more refined measures of LME.

PMID- 17496264
TI  - Long-term impact of celebrity suicide on suicidal ideation: results from a
      population-based study.
AB  - BACKGROUND: The short-term effect of celebrity suicide on the overall suicide
      rate is widely known, but long-term effects remain unclear. OBJECTIVE: To examine
      whether celebrity suicide is associated with suicidal ideation over a longer
      period. DESIGN: This is a study on the effect of the suicide of a famous Hong
      Kong entertainment celebrity, who committed suicide on 1 April 2003, on suicide
      thoughts of the community. A population-based survey was conducted between
      December 2003 and July 2004. Respondents were asked about their suicidal
      ideation, psychological well-being, life events, and whether or not they had been
      affected by celebrity suicide. SETTING: Hong Kong Special Administrative Region,
      the People's Republic of China. PARTICIPANTS: 2016 respondents aged between 20
      and 59 years. RESULTS: After controlling for some known suicide risk factors,
      celebrity suicide was shown to be independently associated with suicidal
      ideation. People who had indicated to have been affected by celebrity suicide
      were 5.93 times (95% CI 2.56% to 13.72%, p = 0) more likely to have severe level
      of suicidal ideation (Adult Suicidal Ideation Questionnaire score > or = 31) than
      people who had not been affected. Respondents having greater anxiety symptoms,
      less reason for living and more focus on irrational values were also found to
      have had their suicide ideation affected by celebrity suicide. CONCLUSIONS:
      Celebrity suicide is a risk factor for suicidal ideation over a short term as
      well as over a long term. Raising awareness of the possible negative effect of
      celebrity suicide through suicide prevention programmes in the community is
      needed.

PMID- 17496266
TI  - A framework for the delivery of public health: an ecological approach.
AB  - The "Framework for the Delivery of Public Health" presented in this paper
      provides a new structure that brings together the multiple components of public
      health, relates them to key influencing factors and provides greater clarity,
      balance and direction for the effective delivery of public health. The paper
      outlines the development of the framework and describes the significance behind
      the key constructs. The symbolisms within the picture and interactions between
      the varied components are compared with the dynamics of an ecosystem; this aims
      to emphasise that improving health occurs within a constantly changing and
      interactive environment. Finally, the applications of the framework are explored,
      including embedding public health within an organisation or setting, assisting in
      strategy development for specific topics and as a training and educational aid.

PMID- 17496265
TI  - Dying of cancer in Italy: impact on family and caregiver. The Italian Survey of
      Dying of Cancer.
AB  - OBJECTIVE: To describe the effect of terminal cancer on the patient's family,
      finances and daily life. METHODS: A cluster sample of 2000 adults (> or = 18
      years old) who had died from cancer, and who were representative of Italy, was
      studied. 1900 caregivers were identified and 68% responded to a post-bereavement
      survey. Caregivers included the patient's child (46%), his/her spouse (31%),
      other relatives or friends (20%) or a health professional (3%). The median age of
      a caregiver was 54 years and 69% were females. During the last 3 months of the
      patient's life, 44% of caregivers reported difficulties in their regular
      employment. RESULTS: Of the 68% of families who had to pay for some of the care,
      37% had to pay for drugs, 36% for nursing and assistance and 22% for physicians.
      Paying for care was more frequent in the south of Italy (OR 2.5; 95% CI 1.0 to
      6.3) and when the patient was a housewife (OR for unit increase 2.7; 95% CI 1.6
      to 6.1). To cover the costs of patient care, 26% of families used all or most of
      their savings. Economic difficulties were greater in the south of Italy (OR 3;
      95% CI 1.8 to 5.1), for female caregivers (OR 1.4; 95% CI 1.0 to 1.9) and for
      disadvantaged patients. The duration of time the patient was completely dependent
      strongly determined the effect caregiving had on their regular employment and on
      the family's financial situation. CONCLUSIONS: Although in Italy families are
      responsible for a small percentage of the overall costs of patient care, the
      effect of cancer on savings and daily life can be substantial. Strong
      geographical and gender differences emerged from this study.

PMID- 17496267
TI  - Cellular spelunking: exploring adipocyte caveolae.
AB  - It has been known for decades that the adipocyte cell surface is particularly
      rich in small invaginations we now know to be caveolae. These structures are
      common to many cell types but are not ubiquitous. They have generated
      considerable curiosity, as manifested by the numerous publications on the topic
      that describe various, sometimes contradictory, caveolae functions. Here, we
      review the field from an "adipocentric" point of view and suggest that caveolae
      may have a function of particular use for the fat cell, namely the modulation of
      fatty acid flux across the plasma membrane. Other functions for adipocyte
      caveolae that have been postulated include participation in signal transduction
      and membrane trafficking pathways, and it will require further experimental
      scrutiny to resolve controversies surrounding these possible activities.

PMID- 17496268
TI  - Proteinuria increases oxylipid concentrations in VLDL and HDL but not LDL
      particles in the rat.
AB  - We previously established that proteinuria alters the apolipoprotein content of
      lipoproteins. This study was conducted to establish whether proteinuria also
      alters the concentrations of oxidized lipids within lipoprotein density
      fractions. To this end, we induced passive Heymann nephritis in Sprague Dawley
      rats and measured an array of alkaline-stable oxylipids in VLDL, LDL, and HDL
      particles. Proteinuria increased the total oxylipid amounts in the HDL and VLDL
      fractions. More importantly, these levels were increased when expressed per unit
      lipoprotein protein, indicating that the oxidized lipid load per particle was
      increased. Epoxides and diols increased approximately 2-fold in HDL and
      approximately 5-fold in VLDL, whereas LDL showed approximately 2-fold decreases.
      The hydroxyeicosatetraenoic acids and hydroxyoctadecadienoic acids (HODEs)
      increased >4-fold in HDL and >20-fold in VLDL, whereas LDL showed approximately 2
      fold decreases in the HODEs. Therefore, nephrotic syndrome alters the lipoprotein
      oxylipid composition independently of an increase in total lipoprotein levels.
      These proteinuria-induced changes may be associated with the cardiovascular risk
      of lipoprotein oxidation.

PMID- 17496269
TI  - Direct evidence of lipid translocation between adipocytes and prostate cancer
      cells with imaging FTIR microspectroscopy.
AB  - Various epidemiological studies show a positive correlation between high intake
      of dietary FAs and metastatic prostate cancer (CaP). Moreover, CaP metastasizes
      to the bone marrow, which harbors a rich source of lipids stored within
      adipocytes. Here, we use Fourier transform infrared (FTIR) microspectroscopy to
      study adipocyte biochemistry and to demonstrate that PC-3 cells uptake
      isotopically labeled FA [deuterated palmitic acid (D(31)-PA)] from an adipocyte.
      Using this vibrational spectroscopic technique, we detected subcellular locations
      in a single adipocyte enriched with D(31)-PA using the upsilon(as+s)(C-D)(2+3)
      (D(31)-PA): upsilon(as+s)(C-H)(2+3) (lipid hydrocarbon) signal. In addition,
      larger adipocytes were found to consist of a higher percentage of D(31)-PA of the
      total lipid found within the adipocyte. Following background subtraction, the
      upsilon(as)(C-D)(2+3) signal illuminated starved PC-3 cells cocultured with D(31)
      PA-loaded adipocytes, indicating translocation of the labeled FA. This study
      demonstrates lipid-specific translocation between adipocytes and tumor cells and
      the use of FTIR microspectroscopy to characterize various biomolecular features
      of a single adipocyte without the requirement for cell isolation and lipid
      extraction.

PMID- 17496270
TI  - CLA differently regulates adipogenesis in stromal vascular cells from porcine
      subcutaneous adipose and skeletal muscle.
AB  - Conjugated linoleic acid (CLA), a mixture of isomers of linoleic acid, has
      previously been shown to be able to decrease porcine subcutaneous (SC) adipose
      tissue levels while increasing the count of intramuscular (IM) adipose tissue in
      vivo. However, the underlying mechanisms through which it acts are poorly
      understood. The objective of this study was to investigate the different effects
      of CLA on adipogenesis in cultured SC adipose tissue and IM stromal vascular
      cells obtained from neonatal pigs. As shown here, trans-10, cis-12 CLA decreased
      the expression of adipocyte-specific genes as well as adipose precursor cell
      numbers and the accumulation of lipid in cultured SC adipose tissue stromal
      vascular cells. However, the cis-9, trans-11 CLA did not alter adipogenesis in SC
      cultures. On the other hand, both CLA isomers increased the expression of
      adipocyte-specific genes in IM cultures, together with the increasing
      accumulation of lipid and Oil Red O-stained cells. Collectively, these data show
      that CLA decreases SC adipose tissue but increases IM adipose tissue by different
      regulation of adipocyte-specific gene expression. These results suggest that
      adipogenesis in IM adipocytes differs from that in SC adipocytes.

PMID- 17496272
TI  - Lack of GNB3 exon 9 polymorphism in primary hypertensive and normotensive dogs.
AB  - The 5500T allele variant of the C5500T single nucleotide polymorphism in the
      human G protein beta3 subunit (GNB3) has been reported to be associated with
      primary hypertension. In this study, the GNB3 gene of primary hypertensive and
      normotensive dogs was examined for an analogous nucleotide polymorphism
      associated with hypertension. The genomic GNB3 dna, with 10 exons and nine
      introns coding for 340 amino acids, is described. PCR product sequencing of the
      GNB3 exon 9 from 25 dogs (including five hypertensive animals) failed to detect
      any nucleotide polymorphism. In contrast to human beings, there was no
      polymorphism at either the analogous nucleotide or in the respective exon. Only
      the human hypertension-associated thymine was detected, regardless of whether the
      dogs were hypertensive or normotensive. Furthermore, examinations of 565 dogs of
      85 distinct breeds for the presence of the human 5500C nucleotide at the
      analogous nucleotide side failed to detect a cytosine that is present with high
      allele frequency in normotensive man. Owing to the lack of allele variance, it is
      concluded that canine primary hypertension is not associated with a polymorphism
      at either the respective human hypertension-associated nucleotide site or in the
      entire exon.

PMID- 17496271
TI  - Evaluation of laboratory tests for SAT serotypes of foot-and-mouth disease virus
      with specimens collected from convalescent cattle in Zimbabwe.
AB  - During a field study in Zimbabwe, clinical specimens were collected from 403
      cattle in six herds, in which the history of foot-and-mouth disease (FMD)
      vaccination and infection appeared to be known with some certainty. Five herds
      had reported outbreaks of disease one to five months previously but clinical FMD
      had not been observed in the sixth herd. A trivalent vaccine (South African
      Territories [SAT] types 1, 2 and 3) had been used in some of the herds at various
      times either before and/or after the recent outbreaks of FMD. The primary aim of
      this study was to evaluate the performance of serological tests for the detection
      of SAT-type FMD virus infection, particularly elisas for antibodies to non
      structural proteins (NSPs) of FMD virus and solid phase competition ELISAS
      (SPCEs) for serotypes SAT1 and SAT2. Secondary aims were to examine NSP
      seroconversion rates in cattle that had been exposed to infection and to compare
      virus detection rates by virus isolation and real-time reverse transcriptase-PCR
      (rtRT-PCR) tests on both oesophagopharyngeal fluids and nasopharyngeal brush
      swabbings. In addition, the hooves of sampled animals were examined for growth
      arrest lines as clinical evidence of FMD convalescence. Laboratory tests provided
      evidence of FMD virus infection in all six herds; SAT2 viruses were isolated from
      oesophagopharyngeal fluids collected from two herds in northern Zimbabwe, and
      SAT1 viruses were isolated from three herds in southern Zimbabwe. Optimised rtRT
      PCR was more sensitive than virus isolation at detecting FMD virus persistence
      and when the results of the two methods were combined for oesophagopharyngeal
      fluids, between 12 and 35 per cent of the cattle sampled in the convalescent
      herds were deemed to be carriers. In contrast, nasopharyngeal swabs yielded only
      two virus-positive specimens. The overall seroprevalence in the five affected
      herds varied with the different NSPS from 56 per cent to 75 per cent, compared
      with 81 per cent and 91 per cent by homologous SPCE and virus neutralisation
      tests respectively. However, if serological test results were considered only for
      the cattle in which persistent infection with FMD virus had been demonstrated, 70
      to 90 per cent scored seropositive in the different NSPs.

PMID- 17496273
TI  - Ultrasonographic evaluation of the size of the adrenal glands of 24 diseased cats
      without endocrinopathies.
AB  - The ultrasonographic measurements of the adrenal glands of 24 diseased cats
      without a clinically or laboratory identifiable endocrinopathy were evaluated
      retrospectively. The mean (sd) thickness of the left adrenal glands was 3.8 (0.8)
      mm and their mean length was 11.3 (2.8) mm; the thickness of the right glands was
      4.5 (1.0) mm and their length was 9.8 (2.4) mm. The products of thickness and
      length were 43.9 (20.2) mm(2) for the left gland and 45.7 (19.7) mm(2) for the
      right gland. There were no significant correlations between the bodyweight, body
      surface area or body condition scores of the cats and the thickness, length or
      the product of thickness and length of either gland.

PMID- 17496274
TI  - Influence of skin testing and blood storage on interferon-gamma production in
      cattle affected naturally with Mycobacterium bovis.

PMID- 17496275
TI  - Bilateral Horner's syndrome in a dog with diabetes mellitus.

PMID- 17496276
TI  - Nor98-like sheep scrapie in the United Kingdom in 1989.

PMID- 17496277
TI  - Gastrocnemius myopathy in yearling beef cattle.

PMID- 17496278
TI  - Maintaining essential veterinary services.

PMID- 17496279
TI  - Out-of-hours emergency cover.

PMID- 17496280
TI  - Out-of-hours emergency cover.

PMID- 17496281
TI  - Anthelmintic resistance in cattle.

PMID- 17496282
TI  - Sheep nasal bot fly and differential diagnosis of bluetongue.

PMID- 17496283
TI  - Cattle fertility problems and Histophilus somni.

PMID- 17496284
TI  - Bilateral renal agenesis in two cavalier King Charles spaniels.

PMID- 17496285
TI  - Haemangiosarcoma in German shepherd dogs.

PMID- 17496286
TI  - Variations in the use of emergency PCI for the treatment of re-infarction
      following intravenous fibrinolytic therapy: impact on outcomes in HERO-2.
AB  - BACKGROUND: Patients who suffer re-infarction during initial hospitalization for
      ST-elevation myocardial infarction (STEMI) have decreased survival compared to
      patients without re-infarction, so treatment of re-infarction may influence
      survival. METHODS AND RESULTS: To determine whether the utilization of
      reperfusion therapies varied within 12 h of re-infarction and was associated with
      30-day mortality, we studied 552 patients with re-infarction of 17,073 patients
      with STEMI enrolled in HERO-2 in five regions (Russia, Eastern Europe, Western
      Countries, Asia, and Latin America). Patients presenting within 6 h of symptom
      onset were randomized to receive either bivalirudin or unfractionated heparin
      intravenously just prior to streptokinase. Re-infarction occurred in 2.8 and 3.6%
      of bivalirudin and heparin treated patients, respectively (P = 0.004), but
      treatment assignment did not influence mortality after re-infarction. Patients
      with re-infarction had a higher 30-day mortality than those without re-infarction
      (24 vs. 10%; P < 0.001 by Cox model). Within 12 h of re-infarction, fibrinolytic
      therapy was administered to 12.0 and 8.2% underwent percutaneous coronary
      intervention (PCI); these two treatments were more frequently utilized in
      patients from Western countries (n = 112), compared to patients from other
      countries (n = 440) (34.8 and 16.1% compared to 6.1 and 6.1%, respectively, P <
      0.001). Mortality was 15% in patients receiving reperfusion therapy for re
      infarction and 27% for those with conservative management, hazard ratio (HR) 0.53
      (95% CI 0.32-0.88), P = 0.01. In multiple Cox regression analysis which included
      adjustment for clinical variables and randomized treatment assignment, 30-day
      mortality after re-infarction varied by region (highest Latin America 29%, lowest
      Western countries 15%; P = 0.01). Other independent prognostic factors included
      age, time from randomization to re-infarction, and Killip class at randomization.
      The HR for PCI treatment of re-infarction was 0.18 [(95% CI 0.04-0.76), P = 0.02]
      in analyses which excluded deaths within 12 h. CONCLUSION: Treatment of re
      infarction with reperfusion therapies was markedly under-utilized, especially in
      non-western countries. PCI for re-infarction, in particular, was associated with
      a lower 30-day mortality, which may reflect both patient selection and effects of
      treatment.

PMID- 17496287
TI  - Comment on: High tigecycline resistance in multidrug-resistant Acinetobacter
      baumannii.

PMID- 17496288
TI  - Impedance cardiography: a useful and reliable tool in optimization of cardiac
      resynchronization devices.
AB  - AIMS: Optimizing cardiac resynchronization therapy (CRT) devices has become more
      complex since modification of both atrioventricular (AV) and interventricular
      (VV) stimulation intervals has become possible. The current paper presents data
      from the routine use of impedance cardiography (IC)-based cardiac output (CO)
      measurements to guide the optimization of AV- and VV-interval timing of CRT
      devices. METHODS AND RESULTS: Forty-six patients with heart failure (left
      ventricular ejection fraction <35%, New York Heart Association (NYHA) III-IV) and
      left bundle branch block (>130 ms) in sinus rhythm were evaluated 3-5 days after
      implantation of a CRT device by means of IC. CO was measured without pacing and
      with biventricular pacing using a standard protocol of VV- and AV-interval
      modification from -60 to +60 ms and 80 to 140 ms, respectively, in 20 ms steps.
      Mean CO without pacing was 3.66 +/- 0.85 L/min and significantly increased to
      4.40 +/- 1.1 L/min (P<0.05) with simultaneous biventricular pacing and an AV
      interval of 120 ms. 'Optimizing' both VV and AV intervals further increased CO to
      4.86 +/- 1.1 L/min (P<0.05). Maximum CO was measured in most patients with left
      ventricular pre-excitation. The proportion of 'non-responders' to CRT was reduced
      by 56% following AV- and VV-interval modification using IC guidance. CONCLUSION:
      Modification of both AV and VV intervals in patients with a CRT device
      significantly improves CO compared with standard simultaneous biventricular
      pacing and no pacing. IC is a useful non-invasive technique for guiding this
      modification. Marked variability of optimal AV and VV intervals between patients
      requires optimization of these intervals for each patient individually.

PMID- 17496289
TI  - Long-term outcomes of patients with acute myocardial infarction.

PMID- 17496290
TI  - Characterization of neutron reference fields at US Department of Energy
      calibration fields.
AB  - The Health Physics Measurements Group at the Los Alamos National Laboratory
      (LANL) has initiated a study of neutron reference fields at selected US
      Department of Energy (DOE) calibration facilities. To date, field
      characterisation has been completed at five facilities. These fields are
      traceable to the National Institute for Standards and Technology (NIST) through
      either a primary calibration of the source emission rate or through the use of a
      secondary standard. However, neutron spectral variation is caused by factors such
      as room return, scatter from positioning tables and fixtures, source anisotropy
      and spectral degradation due to source rabbits and guide tubes. Perturbations
      from the ideal isotropic point source field may impact the accuracy of instrument
      calibrations. In particular, the thermal neutron component of the spectrum, while
      contributing only a small fraction of the conventionally true dose, can
      contribute a significant fraction of a dosemeter's response with the result that
      the calibration becomes facility-specific. A protocol has been developed to
      characterise neutron fields that relies primarily on spectral measurements with
      the Bubble Technology Industries (BTI) rotating neutron spectrometer (ROSPEC) and
      the LANL Bonner sphere spectrometer. The ROSPEC measurements were supplemented at
      several sites by the BTI Simple Scintillation Spectrometer probe, which is
      designed to extend the ROSPEC upper energy range from 5 to 15 MeV. In addition,
      measurements were performed with several rem meters and neutron dosemeters.
      Detailed simulations were performed using the LANL MCNPX Monte Carlo code to
      calculate the magnitude of source anisotropy and scatter factors.

PMID- 17496291
TI  - Characterization and utilization of a Bonner sphere set based on gold activation
      foils.
AB  - Bonner sphere (BS) sets which use activation foils as the central thermal neutron
      sensor have advantages over active BS systems in certain environments, for
      example, pulsed fields, or fields with high photon components. In such
      environments, they may be the only type of neutron spectrometer which can be
      used. This paper describes work, using both measurements and calculations, to
      validate the response functions for a BS set based on gold activation foils. As
      an illustration of the use of such a system, a measurement is described of the
      contaminant neutron spectrum in the treatment room of a 21 MV hospital linear
      accelerator providing photon beams for radiotherapy.

PMID- 17496292
TI  - The problems associated with the monitoring of complex workplace radiation fields
      at European high-energy accelerators and thermonuclear fusion facilities.
AB  - The European Commission is funding within its Sixth Framework Programme a three
      year project (2005-2007) called CONRAD, COordinated Network for RAdiation
      Dosimetry. The organisational framework for this project is provided by the
      European Radiation Dosimetry Group EURADOS. One task within the CONRAD project,
      Work Package 6 (WP6), was to provide a report outlining research needs and
      research activities within Europe to develop new and improved methods and
      techniques for the characterisation of complex radiation fields at workplaces
      around high-energy accelerators, but also at the next generation of thermonuclear
      fusion facilities. The paper provides an overview of the report, which will be
      available as CERN Yellow Report.

PMID- 17496293
TI  - On the neutron contribution to the exposure level onboard space vehicles.
AB  - The neutron contribution to the spacecraft crew exposure could represent an
      important part of the total dose equivalent value. The determination of this
      contribution represents a rather complex and difficult task, both through
      experimental and theoretical estimation. This paper will present an attempt to
      determine the neutron contribution onboard the International Space Station and
      Foton capsule using the data measured by means of a Si-diode based energy
      deposition spectrometer. As such a spectrometer, the MDU-Liulin equipment,
      developed in one of our laboratories was used. The equipment allows the data
      accumulated during the passage in or out of the South Atlantic Anomaly (SAA). In
      this paper, only the data obtained out of the SAA were analysed, assuming that
      the neutron spectra are similar to those onboard aircraft and/or at the CERF high
      energy radiation field. The excess of deposited energy in the region above 1 MeV,
      when comparing with the aircraft field, was expected to represent the primary
      high-energy charged particles. Total dosimetry characteristics obtained in this
      way are in reasonable agreement with other data, neutron contribution
      representing approximately 40% of the total dose equivalent for the flight
      duration outside of the SAA.

PMID- 17496294
TI  - Light charged-particle production in 96 MeV neutron-induced reactions on carbon
      and oxygen.
AB  - In recent years, an increasing number of applications involving fast neutrons
      have been developed or are under consideration, e.g. radiation treatment of
      cancer, neutron dosimetry at commercial aircraft altitudes, soft-error effects in
      computer memories, accelerator-driven transmutation of nuclear waste and energy
      production and determination of the response of neutron detectors. Data on light
      ion production in light nuclei such as carbon, nitrogen and oxygen are
      particularly important in calculations of dose distributions in human tissue for
      radiation therapy at neutron beams, and for dosimetry of high-energy neutrons
      produced by high-energy cosmic radiation interacting with nuclei (nitrogen and
      oxygen) in the atmosphere. When studying neutron dose effects, it is especially
      important to consider carbon and oxygen, since they are, by weight, the most
      abundant elements in human tissue. Preliminary experimental double-differential
      cross sections of inclusive light-ion (p, d, t, (3)He and alpha) production in
      carbon induced by 96-MeV neutrons have been presented. Energy spectra were
      measured at eight laboratory angles: 20, 40, 60, 80, 100, 120, 140 and 160
      degrees. Measurements were performed at The Svedberg Laboratory (TSL), Uppsala,
      using the dedicated MEDLEY experimental setup. The authors have earlier reported
      experimental double-differential cross sections of inclusive light-ion production
      in oxygen. In this paper, the deduced kerma coefficients for oxygen has been
      presented and compared with reaction model calculations.

PMID- 17496295
TI  - Pre- and post-irradiation fading of 6LiF:Mg,Ti (TLD-600) exposed to thermal
      neutrons.
AB  - The results of (6)LiF:Mg,Ti (TLD-600) glow peaks fading after irradiation by
      thermal neutrons, as a function of pre- and post-irradiation times up to 3
      months, are presented. The measured glow curves were analysed using the
      computerised glow curve deconvolution and region of integration methods, to study
      the decay characteristics of each individual peak and the sum of selected peak
      areas in the glow curve. The results confirm a high stability for the sum of
      peaks 4 + 5 and 6 + 7, whereas peaks 2 and 3 have a dominant contribution to the
      fading effect.

PMID- 17496296
TI  - Measurement and calculation of the emission anisotropy of an X1 252Cf neutron
      source.
AB  - The authors have measured the emission anisotropy from a (252)Cf spontaneous
      fission neutron source in an X1 encapsulation. The measurements were made in a
      large low-scatter laboratory using a long counter, and data were taken at angles
      varying in 10 degrees steps from 0 degrees to 180 degrees relative to the
      cylindrical axis of the source. Corrections were made for room scatter, loss of
      neutrons due to air scatter and detector dead time. Calculations corresponding to
      these measurements were subsequently carried out using the two Monte Carlo codes
      MCNP and MCBEND, and the results are compared with the measurements and with each
      other.

PMID- 17496297
TI  - Calibration of personal dosemeters in mixed neutron-photon fields: some problems
      and their solution.
AB  - In neutron reference radiation fields, the conventional true value of the
      personal dose equivalent, H(p)(10), is derived from the spectral neutron fluence
      and recommended conversion coefficients. This procedure requires the phantom on
      which the personal dosemeter is mounted to be irradiated with a broad and
      parallel beam. In many practical situations, the change of the neutron fluence
      and/or the energy distribution over the surface of the phantom may not be
      neglected. For a selection of typical irradiation conditions in neutron reference
      radiation fields, the influence of this effect has been analysed using numerical
      methods. A further problem, which is of relevance for the calibration of
      dosemeters measuring both the neutron and the photon component of mixed fields,
      is the 'double counting' of the dose equivalent due to neutron-induced photons.
      The relevance of this conceptual problem for calibrations in mixed-field
      dosimetry was analysed.

PMID- 17496298
TI  - Design and characterisation of a pulsed neutron interrogation facility.
AB  - The Joint Research Centre recently obtained a license to operate a new
      experimental device intended for research in the field of nuclear safeguards. The
      research projects currently being planned for the new device includes mass
      determination of fissile materials in matrices and detection of contraband non
      nuclear materials. The device incorporates a commercial pulsed neutron generator
      and a large graphite mantle surrounding the sample cavity. In this configuration,
      a relatively high thermal neutron flux with a long lifetime is achieved inside
      the sample cavity. By pulsing the neutron generator, a sample may be interrogated
      by a pure thermal neutron flux during repeated time periods. The paper reports on
      the design of the new device and the pulsed fast and thermal neutron source. The
      thermal neutron flux caused by the neutron generator and the graphite structure
      has been characterised by foil activation, fission chamber and (3)He proportional
      counter measurements.

PMID- 17496299
TI  - New descriptors of radiation quality based on nanodosimetry, a first approach.
AB  - After a short overview on the latest developments in nanodosimetry, measured
      frequency distributions of ionisation cluster size caused by 4.6 MeV alpha
      particles or low-energy electrons in 'nanometric' volumes of nitrogen are
      compared with cluster-size distributions for liquid water cylinders that are
      equal in size to segments of DNA of 10 base-pairs length. Such frequency
      distributions are, to a greater part, governed by the same basic physical
      interaction data as those to be expected, if charged particles interact with DNA
      segments. Quantities derived from ionisation cluster-size distributions should,
      therefore, behave as a function of radiation quality similarly to the yields of
      single or double strand breaks in the DNA. To test this assumption, extensive
      Monte Carlo simulations were performed for electrons in the energy range between
      12.5 eV and 100 keV for protons at energies between 0.7 MeV and 250 MeV and for
      alpha-particles in the energy range between 2 MeV and 100 MeV. The results are
      then compared with the yields of single- or double-strand breaks in the DNA,
      taken from the literature.

PMID- 17496300
TI  - Nuclear theory for high-energy nuclear reactions of biomedical relevance.
AB  - A full description of all possible nuclear reactions that take place in a
      macroscopic device can only be accomplished with a nuclear model code in
      combination with key experimental data. To address this issue, the authors
      demonstrate some of the capabilities of TALYS, a nuclear reaction program which
      simulates nuclear reactions that involve neutrons, gamma rays, protons,
      deuterons, tritons, helions and alpha particles, in the 1 keV to 200 MeV energy
      range. A suite of nuclear reaction models has been implemented into a single code
      system, enabling to evaluate basically all nuclear reactions beyond the resonance
      range. The main nuclear models used, such as newly developed optical models,
      various compound nucleus, fission, gamma-ray strength, level density and pre
      equilibrium models, all driven by a comprehensive database of nuclear structure
      parameters have been briefly mentioned. The predictive power of the code is
      demonstrated by comparing calculated results with a diverse set of experimental
      observables. The aim is to show that TALYS represents a robust computational
      approach that covers the whole path from fundamental nuclear reaction models to
      the creation of complete data libraries for nuclear applications.

PMID- 17496301
TI  - Darwin: dose monitoring system applicable to various radiations with wide energy
      ranges.
AB  - A new radiation dose monitor, designated as DARWIN (Dose monitoring system
      Applicable to various Radiations with Wide energy ranges), has been developed for
      real-time monitoring of doses in workspaces and surrounding environments of high
      energy accelerator facilities. DARWIN is composed of a phoswitch-type
      scintillation detector, which consists of liquid organic scintillator BC501A
      coupled with ZnS(Ag) scintillation sheets doped with (6)Li, and a data
      acquisition system based on a Digital-Storage-Oscilloscope. DARWIN has the
      following features: (1) capable of monitoring doses from neutrons, photons and
      muons with energies from thermal energy to 1 GeV, 150 keV to 100 MeV and 1 MeV to
      100 GeV, respectively, (2) highly sensitive with precision and (3) easy to
      operate with a simple graphical user-interface. The performance of DARWIN was
      examined experimentally in several radiation fields. The results of the
      experiments indicated the accuracy and wide response range of DARWIN for
      measuring dose rates from neutrons, photons and muons with wide energies. It was
      also found from the experiments that DARWIN enables us to monitor small
      fluctuations of neutron dose rates near the background level because of its high
      sensitivity. With these properties, DARWIN will be able to play a very important
      role for improving radiation safety in high-energy accelerator facilities.

PMID- 17496302
TI  - Gel dosimetry in the BNCT facility for extra-corporeal treatment of liver cancer
      at the HFR Petten.
AB  - A thorough evaluation of the dose inside a specially designed and built facility
      for extra-corporeal treatment of liver cancer by boron neutron capture therapy
      (BNCT) at the High Flux Reactor (HFR) Petten (The Netherlands) is the necessary
      step before animal studies can start. The absorbed doses are measured by means of
      gel dosemeters, which help to validate the Monte Carlo simulations of the
      spheroidal liver holder that will contain the human liver for irradiation with an
      epithermal neutron beam. These dosemeters allow imaging of the dose due to gammas
      and to the charged particles produced by the (10)B reaction. The thermal neutron
      flux is extrapolated from the boron dose images and compared to that obtained by
      the calculations. As an additional reference, Au, Cu and Mn foil measurements are
      performed. All results appear consistent with the calculations and confirm that
      the BNCT liver facility is able to provide an almost homogeneous thermal neutron
      distribution in the liver, which is a requirement for a successful treatment of
      liver metastases.

PMID- 17496303
TI  - Construction of monoenergetic neutron calibration fields using 45Sc(p, n)45Ti
      reaction at JAEA.
AB  - The 8 and 27 keV monoenergetic neutron calibration fields have been developed by
      using (45)Sc(p, n)(45)Ti reaction. Protons from a 4-MV Pelletron accelerator are
      used to bombard a thin scandium target evaporated onto a platinum disc. The
      proton energies are finely adjusted to the resonance to generate the 8 and 27 keV
      neutrons by applying a high voltage to the target assemblies. The neutron
      energies were measured using the time-of-flight method with a lithium glass
      scintillation detector. The neutron fluences at a calibration point located at 50
      cm from the target were evaluated using Bonner spheres. A long counter was placed
      at 2.2 m from the target and at 60 degrees to the direction of the proton beam in
      order to monitor the fluence at the calibration point. Fluence and dose
      equivalent rates at the calibration point are sufficient to calibrate many types
      of the neutron survey metres.

PMID- 17496304
TI  - A monitor for neutron flux measurements up to 20 MeV.
AB  - A liquid scintillation detector aimed for neutron energy and fluence measurements
      in the energy region <20 MeV has been calibrated using monoenergetic and white
      spectrum neutron fields. Careful measurements of the proton light output function
      and the response matrix have been performed allowing for the application of
      unfolding techniques using existing codes. The response matrix is used to
      characterise monoenergetic neutron fields produced by the T(d,n) at a low-energy
      deuteron accelerator installed at the Swedish Defense Research Agency (FOI).

PMID- 17496305
TI  - A first class service? Setting the standard of care for the contemporary NHS.

PMID- 17496306
TI  - Trends in alcohol consumption in Singapore 1992 2004.
AB  - AIMS: To present trends in alcohol consumption between 1992 and 2004 in
      Singapore. METHODS: Alcohol consumption data were derived from national health
      surveys conducted in 1992, 1998 and 2004. Age-adjusted prevalence of frequent
      (drinking 1-4 days a week), regular (drinking more than 4 days a week) and binge
      (having five or more drinks during a drinking session at least once in the month)
      drinking by gender and age group for the three surveys were compared.
      Multivariate analyses for binge drinking in 2004 were performed using logistic
      regression models. RESULTS: Prevalence of frequent, regular and binge drinking
      increased between 1992 and 2004. Prevalence increase in binge drinking was
      highest (from 5.1 to 10.0%), followed by frequent drinking (from 4.5 to 7.5%) and
      regular drinking (from 2.9 to 3.1%). Uptake in binge drinking increased in both
      genders and across all age groups but was most evident among adults aged 18-29.
      Frequent drinking increase was observed for both genders but was most pronounced
      among women aged 18-29. The level of regular drinking declined in men but
      increased in women, especially those aged 18-29 and 30-49. Being younger, male,
      separated, divorced or widowed, a current smoker, or having a monthly household
      income of S$6000 and above were attributes positively associated with binge
      drinking. CONCLUSIONS: Alcohol consumption, especially binge drinking, has
      increased among Singaporeans between 1992 and 2004. There is gender convergence
      in alcohol consumption.

PMID- 17496308
TI  - Systematic review of cytoreductive surgery and heated intraoperative
      intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis in
      primary and recurrent ovarian cancer.
AB  - The aim of this systematic review is to critically evaluate cytoreductive surgery
      combined with heated intraoperative intraperitoneal chemotherapy in the treatment
      of ovarian cancer. A systematic review of all manuscripts published in the
      English literature that met predetermined inclusion criteria was carried out.
      Data concerning cytoreductive surgery, method and agents for administration of
      heated intraoperative intraperitoneal chemotherapy, morbidity, mortality,
      hospital stay and survival were extracted, critically reviewed and tabulated.
      Fourteen studies were analyzed. A wide variety of drug doses, methods of
      intraperitoneal chemotherapy administration and volume of chemotherapy solution
      were used. Seven studies showed that patients with complete cytoreduction had the
      greatest benefit. The median overall survival for primary and recurrent disease
      ranged from 22 to 54 months and the median disease-free survival from 10 to 26
      months. The rates of significant morbidity associated with this combined
      treatment were low, ranging from 5% to 36%. The median mortality was 3% (range 0%
      10%). Cytoreductive surgery combined with heated intraoperative intraperitoneal
      chemotherapy is a treatment option for patients with ovarian cancer that is
      worthy of further investigation. Selection criteria for patients most likely to
      benefit need to be defined.

PMID- 17496307
TI  - Peripheral blood natural killer cell count is associated with clinical outcome in
      patients with aaIPI 2-3 diffuse large B-cell lymphoma.
AB  - BACKGROUND: Lymphocytopenia is a prognostic factor in Hodgkin's disease. In
      diffuse large B-cell lymphoma (DLBCL), data are much less established, in spite
      of numerous reports on immune system-lymphoma interactions. This study addresses
      the prognostic value of blood lymphocyte subsets at diagnosis in DLBCL. PATIENTS
      AND METHODS: Absolute values of blood lymphocyte subsets and monocytes were
      prospectively determined by flow cytometry in 140 patients with 2 or 3 adverse
      age-adjusted International Prognostic Index (aaIPI) factors included in a Groupe
      d'Etude des Lymphomes de l'Adulte protocol (LNH98B3). Absolute cell counts at
      diagnosis and aaIPI were evaluated with regard to clinical outcome. RESULTS: Low
      median cell counts of 337, 211, and 104/mul were evidenced for the CD4+, CD8+ T,
      and natural killer (NK) cells, respectively. In univariate analysis, only NK cell
      count [odds ratio (OR) = 1.81 (1.27, 2.57), P = 0.001] and aaIPI [OR = 2.29
      (0.95, 5.45), P = 0.06] were associated with induction treatment response. Low NK
      cell count [Hazard ratio (HR) = 1.27 (1.06, 1.52), P = 0.01] and aaIPI 3 [HR =
      1.95 (1.20, 3.16), P = 0.01] were also associated with a shorter event free
      survival (EFS). In multivariate analysis, NK cell count was associated with
      response [OR = 1.77 (1.24, 2.54), P = 0.002] and EFS [HR = 1.25 (1.04, 1.50) P =
      0.02] independently of aaIPI. CONCLUSIONS: This study shows an association
      between circulating NK cell number and clinical outcome in DLBCL, possibly
      important in the context of the broadening use of rituximab, a likely NK
      dependent therapy.

PMID- 17496309
TI  - Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients
      with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy.
AB  - BACKGROUND: High-dose therapy (HDT) with stem-cell support is the reference
      treatment for relapsed lymphoma, but is not appropriate for all patients.
      Conventional salvage chemotherapies have been used with limited efficacy and
      significant toxicity. Rituximab, gemcitabine and oxaliplatin are active as single
      agents in relapsed or refractory lymphoma, and have demonstrated synergistic
      effects in vitro and in vivo. PATIENTS AND METHODS: Forty-six patients with
      relapsed or refractory B-cell lymphoma received up to eight cycles of R-GemOx
      (rituximab 375 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) and oxaliplatin 100
      mg/m(2) on day 2). The majority (72%) had diffuse large B-cell lymphoma. RESULTS:
      After four cycles of R-GemOx, the overall response rate was 83% [50% complete
      response (CR)/unconfirmed CR (CRu)]. High CR/CRu rates were observed in all
      histological subtypes. In patients who had previously received rituximab, the
      CR/CRu rate after eight cycles was 65%. The 2-year event-free and overall
      survival rates (median follow-up of 28 months) were 43% and 66%, respectively.
      Among responders, the probability of being disease free for 2 years was 62%.
      Treatment was generally well tolerated. CONCLUSION: R-GemOx shows promising
      activity with acceptable toxicity in patients with relapsed/refractory B-cell
      lymphoma who are not eligible for HDT.

PMID- 17496310
TI  - Polymorphism in cytokine genes as prognostic markers in Hodgkin's lymphoma.
AB  - BACKGROUND: In Hodgkin's lymphoma (HL), the production of cytokines by Reed
      Sternberg cells and the surrounding tissue is thought to contribute to the
      biology of the disease. Cytokine expression can be altered by common single
      nucleotide polymorphisms (SNPs) in the 5'-promoter regions. PATIENTS AND METHODS:
      We studied polymorphic allele variants of the cytokine genes interleukin (IL)-10
      (T-3575A, G-2849A, C-2763A, A-1082G and C-592A), IL-6 (G-174C) and tumor necrosis
      factor-alpha (C-863A and G-308A) in 184 patients with HL, and analyzed for
      associations with treatment outcome. RESULTS: Carriers of the IL-10-592AA and the
      IL-6-174GG genotypes had a significantly lower probability of freedom from
      treatment failure (FFTF) with adjusted hazard ratios (HRs) for failure of 2.92
      [95% CI (confidence interval) 1.58-5.41, P = 0.001] and of 1.75 (95% CI 1.04
      2.92, P = 0.03), respectively. Reconstructing haplotypes from the five SNPs in
      the IL-10 promoter revealed that homozygous carriers of the IL-10.4 haplotype (T
      G-C-A-A) had a worse FFTF (HR, 2.35; 95% CI 1.2-4.6, P = 0.01). In the Cox
      multivariate analysis, the IL-10-592AA, the IL-6-174GG genotypes and stage were
      independent prognostic factors. CONCLUSIONS: Our study indicates that cytokine
      genotypes predict clinical outcome in patients with HL and points to the
      importance of the genetic background of the host for treatment response.

PMID- 17496312
TI  - The general epidemiologist: is there a place in today's epidemiology?
AB  - Epidemiology has changed remarkably during its growth in the past quarter
      century. One of those changes has been the ever-increasing specialization among
      its practitioners. In this commentary, the author explores the degree to which
      this phenomenon has shaped the field. A partial explanation for this trend is
      found in the decline in the availability of training funds not focused on
      specific disease areas. Although it appears likely that epidemiology can continue
      to flourish without general epidemiologists, the field will lose some of its
      ability to quickly respond to emerging public health challenges. The author
      considers steps necessary for the training and inclusion of general
      epidemiologists.

PMID- 17496311
TI  - Genetic susceptibility according to three metabolic pathways in cancers of the
      lung and bladder and in myeloid leukemias in nonsmokers.
AB  - BACKGROUND: We chose a set of candidate single nucleotide polymorphisms (SNPs) to
      investigate gene-environment interactions in three types of cancer that have been
      related to air pollution (lung, bladder and myeloid leukemia). PATIENTS AND
      METHODS: The study has been conducted as a nested case-control study within the
      European Prospective Investigation into Cancer and Nutrition cohort (409 cancer
      cases and 757 matched controls). We included never and ex-smokers. SNPs were in
      genes involved in oxidative stress, phase I metabolizing genes, phase II
      metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). RESULTS: The
      most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio
      (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33
      3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD
      and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73
      37.3; homozygotes). Other statistically significant associations were found in
      subgroups defined by smoking habits (never or ex-smokers), environmental tobacco
      smoke or gender, with no obvious pattern. When gene variants were organized
      according to the three main pathways, the emerging picture was of a strong
      involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4)
      for those having three or more variant alleles. The association was considerably
      stronger for leukemias arising before the age of 55.

PMID- 17496313
TI  - Association of periconceptional multivitamin use and risk of preterm or small-for
      gestational-age births.
AB  - The authors' objective was to determine the relation between periconceptional
      multivitamin use and the risk of small-for-gestational-age (SGA: <5th percentile;
      5th-<10th percentiles) or preterm (<34 weeks; 34-<37 weeks) births. Women in the
      Pregnancy Exposures and Preeclampsia Prevention Study (1997-2001) reported at
      enrollment their regular multivitamin use in the past 6 months (n=1,823). Women
      were classified as users or nonusers in multinomial logistic models. After
      adjustment for race, age, education, enrollment gestational age, and household
      density, periconceptional multivitamin use was associated with a reduced risk of
      preterm births (<34 weeks) (odds ratio (OR)=0.29, 95% confidence interval (CI):
      0.13, 0.64) and spontaneous preterm births (<34 weeks) (OR=0.40, 95% CI: 0.16,
      0.99). Risk of SGA (<5th percentile) was marginally lower (OR=0.64, 95% CI: 0.40,
      1.03) after adjustment for smoking, education, parity, enrollment gestational
      age, and body mass index. Prepregnancy body mass index modified this relation.
      Nonobese users had a reduction (OR=0.54, 95% CI: 0.32, 0.91) in risk of SGA (<5th
      percentile); there was no effect among obese women. There was no effect of
      multivitamin use on risk of preterm births (34-<37 weeks) or SGA (5th-<10th
      percentiles). Sensitivity analysis for unmeasured confounding by folate intake
      supported these findings. Study results indicate lower rates of severe preterm
      births and extreme SGA in women who report periconceptional vitamin use, although
      these should be considered cautiously until replicated.

PMID- 17496314
TI  - Hepatitis C virus infection and the development of type 2 diabetes in a community
      based longitudinal study.
AB  - The temporal relation of hepatitis C virus (HCV) infection to the development of
      type 2 diabetes remains unknown. The authors followed 4,958 persons aged > or =40
      years without diabetes (3,486 seronegative, 812 anti-HCV+, 116 with hepatitis B
      virus/HCV coinfection, and 544 hepatitis B surface antigen (HBsAg)+) from a
      community-wide cohort in southern Taiwan for 7 years (1997-2003) to study the
      risk of diabetes associated with HCV infection. A total of 474 participants
      developed diabetes. The 7-year cumulative incidence was 7.5% for HBsAg+, 8.6% for
      seronegative, 14.3% for anti-HCV+, and 14.7% for coinfected participants.
      Compared with HCV- persons, HCV+ persons had a higher cumulative incidence of
      diabetes (log-rank test, p < 0.0001). A multivariate Cox proportional hazards
      model showed that anti-HCV+ (hazard ratio = 1.7, 95% confidence interval: 1.3,
      2.1), coinfection (hazard ratio = 1.7), overweight, obesity, and increasing age
      were significantly associated with diabetes (p < 0.05). Gender, educational
      level, HBsAg+ status, alcohol consumption, and smoking were not significant.
      After stratification by age and body mass index, the risk ratio for diabetes in
      anti-HCV+ participants increased when age decreased and body mass index levels
      increased (p < 0.001). Results show that HCV infection is an independent
      predictor of diabetes, especially for anti-HCV+ persons who are younger or have a
      higher body mass index.

PMID- 17496315
TI  - Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine
      model of asthma via regulatory T cells.
AB  - We previously reported high levels of the soluble form of the IL-6R (sIL-6R) in
      the airways of asthmatic subjects. Here, we analyzed the IL-6R effects on Th2
      cell survival in the lung by locally antagonizing sIL-6R-mediated trans-signaling
      with a designer fusion protein (gp130-Fc) as well as IL-6R signaling with an
      antibody against the gp80 unit of the IL-6R (alphaIL-6R) in a murine model of
      asthma after ovalbumin peptide (OVA) sensitization and challenge. Blockade of the
      sIL-6R led to a significant decrease in inflammatory cells by an apoptosis
      independent mechanism. In contrast, local treatment with alphaIL-6R antibodies
      that also block signaling via the membrane-bound IL-6R (mIL-6R) led to decreased
      signal transducers and activators of transcription (STAT)-3 but not STAT-1
      phosphorylation in the lung of treated mice as compared with control-treated
      mice. Moreover, this treatment induced apoptosis of the cells present in the
      airways of OVA-treated mice as well as apoptosis of lung CD4+ effector T cells.
      Subsequent studies showed that this effect was mediated by lung CD4+CD25+Foxp3+ T
      regulatory cells by a cell-cell interaction, thereby contributing to the
      resolution of airway hyperresponsiveness in OVA-treated mice given anti-IL-6R
      antibodies. Taken together, these data suggest that blockade of mIL-6R signaling
      leads to cell death of lung effector T cells by activating regulatory T cells in
      experimental asthma. Local targeting of IL-6R signaling could be a novel approach
      for inducing Th2 T cell death in allergic airways via regulatory T cells.

PMID- 17496316
TI  - FGF 10 and Sprouty 2 modulate trophoblast invasion and branching morphogenesis.
AB  - Branching morphogenesis (BM) of the chorionic villous tree is a crucial component
      of early placental formation. Fibroblast growth factors (FGFs), their receptor
      tyrosine kinase (RTK) and negative regulators like Sprouty (Spry) proteins are
      pivotal factors in the development of diverse branching organ systems. The aim of
      this study was to examine the effect of FGF10 and Sprouty 2 on BM of the
      chorionic villi in vitro. Villous explants of first trimester placentas were
      cultured and their outgrowths were monitored. The effect of FGF10 was tested on
      matrigel migration/invasion assay, collagenolytic activity of single cell
      trophoblasts and on villous explants outgrowths. siRNA of Spry2 was used to
      reduce its expression and to investigate the role of Sprouty 2 in villous
      explants outgrowths. Quantitative RT-PCR and immunohistochemistry were performed
      to determine Sprouty 2 and HLA-G (a marker of invasion) expression. FGF 10
      stimulated by 8-fold the migration/invasion of single cell trophoblast enhanced
      their collagenolytic activity. Reduction of Spry2 expression in villous explants
      showed a marked increase in villous outgrowths. This was accompanied by enhanced
      staining for HLA-G and by the reduction of Spry2 expression that was confirmed by
      immunohistochemistry and by quantitative RT-PCR. We conclude that trophoblast
      outgrowth and invasion (part of placental villi sprouting) at the fetal maternal
      interface is in part under delicate control of FGF 10 and Sprouty 2. FGF 10
      promotes invasion and outgrowth of trophoblasts. In addition, it increases Spry2
      expression, which attenuates trophoblast sprouting.

PMID- 17496317
TI  - OBO to OWL: a protege OWL tab to read/save OBO ontologies.
AB  - The Open Biomedical Ontologies (OBO) format from the GO consortium is a very
      successful format for biomedical ontologies, including the Gene Ontology. But it
      lacks formal computational definitions for its constructs and tools, like DL
      reasoners, to facilitate ontology development/maintenance. We describe the OBO
      Converter, a Java tool to convert files from OBO format to Web Ontology Language
      (OWL) (and vice versa) that can also be used as a Protege Tab plug-in. It uses
      the OBO to OWL mapping provided by the National Center for Biomedical Ontologies
      (NCBO) (a joint effort of OBO developers and OWL experts) and offers options to
      ease the task of saving/reading files in both formats. AVAILABILITY:
      bioontology.org/tools/oboinowl/obo_converter.html. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 17496318
TI  - Rapid assessment of correlated amino acids from pair-to-pair (P2P) substitution
      matrices.
AB  - Identification of correlated amino acids in proteins has been a topic of broad
      interest in view of its functional implications and importance in protein design.
      A new set of pair-to-pair (P2P) substitution matrices for amino acids was
      recently introduced as a useful tool for inferring information on such correlated
      sites. We present a website developed for automated application of these matrices
      for analysis of query sequences. The site offers options for graphical analysis
      of correlations, as well as visualization of correlated amino acids on
      representative, structurally characterized, members of the examined family of
      sequences. AVAILABILITY: http://www.ccbb.pitt.edu/p2p.

PMID- 17496319
TI  - DoriC: a database of oriC regions in bacterial genomes.
AB  - Replication origins (oriCs) of bacterial genomes currently available in GenBank
      have been predicted by using a systematic method comprising the Z-curve analysis
      for nucleotide distribution asymmetry, DnaA box distribution, genes adjacent to
      candidate oriCs and phylogenetic relationships. These oriCs are organized into a
      MySQL database, DoriC, which provides extensive information and graphical views
      of the oriC regions. In addition, users can Blast a query sequence or even a
      whole genome against DoriC to find a homologous one. DoriC will be updated timely
      and the latest version is DoriC 1.8, in which oriCs of 425 genomes (468
      chromosomes) are identified. AVAILABILITY: DoriC can be accessed from
      http://tubic.tju.edu.cn/doric/. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at http://tubic.tju.edu.cn/doric/supplementary.htm.

PMID- 17496320
TI  - GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor.
AB  - Microarray technology has become a standard molecular biology tool. Experimental
      data have been generated on a huge number of organisms, tissue types, treatment
      conditions and disease states. The Gene Expression Omnibus (Barrett et al.,
      2005), developed by the National Center for Bioinformatics (NCBI) at the National
      Institutes of Health is a repository of nearly 140,000 gene expression
      experiments. The BioConductor project (Gentleman et al., 2004) is an open-source
      and open-development software project built in the R statistical programming
      environment (R Development core Team, 2005) for the analysis and comprehension of
      genomic data. The tools contained in the BioConductor project represent many
      state-of-the-art methods for the analysis of microarray and genomics data. We
      have developed a software tool that allows access to the wealth of information
      within GEO directly from BioConductor, eliminating many the formatting and
      parsing problems that have made such analyses labor-intensive in the past. The
      software, called GEOquery, effectively establishes a bridge between GEO and
      BioConductor. Easy access to GEO data from BioConductor will likely lead to new
      analyses of GEO data using novel and rigorous statistical and bioinformatic
      tools. Facilitating analyses and meta-analyses of microarray data will increase
      the efficiency with which biologically important conclusions can be drawn from
      published genomic data. AVAILABILITY: GEOquery is available as part of the
      BioConductor project.

PMID- 17496321
TI  - BioMoby web services to support clustering of co-regulated genes based on
      similarity of promoter configurations.
AB  - Here we present a computational protocol to analyze the promoter regions of a
      given set of co-expressed genes, and its implementation through the use of Web
      services technologies. This protocol aims to cluster a set of co-regulated genes
      in subsets of genes showing similar configurations of transcription factor
      binding sites. All the steps of this protocol have been developed as web services
      that are compliant with BioMoby specifications. AVAILABILITY:
      {http://genome.imim.es/cgi-bin/moby/GeneClustering_DataSubmission.cgi}.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at
      {http://genome.imim.es/webservices/}

PMID- 17496322
TI  - A review of 116 cases of breastfeeding-associated hypernatremia in rural area of
      central Turkey.
AB  - We aimed to assess the incidence, neurologic and neurodevelopmental outcome of
      breastfeeding-associated hypernatremic dehydration among hospitalized neonates in
      rural area of central Turkey. A retrospective study was conducted at Gevher
      Nesibe Hospital over a 6-year period, to identify otherwise healthy term and near
      term (> or = 35 weeks of gestation) breastfed neonates (<29 days of age) who were
      admitted with serum sodium concentrations of >150 mEq/l and no explanation for
      hypernatremia other than inadequate milk intake. The incidence of breastfeeding
      associated hypernatremic dehydration among hospitalized term and near-term
      neonates (n = 5592) was 2.1%, occurring for 116 breastfed infants. More than one
      half of the infants admitted with breastfeeding-associated hypernatremia
      exhibited abnormal development at 12 or more months of age. Increased efforts are
      required to establish successful breastfeeding.

PMID- 17496323
TI  - A 5-year PICU experience of disseminated staphylococcal disease, part 2:
      management, critical care needs and outcome.
AB  - Staphylococcus aureus causes an impressive spectrum of disease in tropics and
      subtropics. Scanty data are available regarding disseminated staphylococcal
      disease (DSD) in children, especially on their critical care needs. It is
      important to recognize and prioritize patients who may benefit most from
      Pediatric Critical Care. The objective of this article is to review the, critical
      care needs, management and outcome of patients with DSD and to identify clinical
      indicators for need of critical care. The study setting is a Pediatric Intensive
      Care Unit of an urban tertiary care teaching hospital in a developing economy.
      Fifty-three patients (age, 1 month to 12 years) with DSD, admitted to PICU during
      June 1994 to June 1999, form the subjects for the study. DSD was defined as
      involvement of at least two distant organs with presence of Gram-positive cocci
      in clusters and/or growth of S. aureus from at least one normally sterile body
      fluid. Data regarding demographic and clinical picture, microbiological profile,
      indication for PICU admission, monitoring needs, medical and surgical management
      and outcome was retrieved from the case records. Critical care problems included
      septic shock (28/53), pericardial effusion (21/53, cardiac tamponade in six),
      raised intracranial pressure (5 patients) and refractory status epilepticus (1
      patient). The majority developed septic shock after first few doses of parenteral
      antimicrobials. They required an impressive amount of fluid [100 (56) ml/kg]
      during initial 6 h of resuscitation, and 90% had myocardial dysfunction requiring
      inotropic support. Tracheal intubation was needed in 18 (34%) and ventilatory
      support in 17 (32%) patients. About 60% patients had metabolic abnormalities.
      Soft tissue disease was associated with high risk of septic shock (RR, 1.77; P <
      0.05). Presence of both septic shock and need for ventilation was associated with
      high mortality (RR, 20.5; P < 0.001). Patients with suspected DSD need intensive
      cardio-respiratory monitoring during initial 48-72 h of therapy; and those who
      develops shock, respiratory failure, pericardial effusion and necrotizing soft
      tissue disease should be prioritized for PICU admission.

PMID- 17496324
TI  - Evaluation of immunochromatography tests for detection of rotavirus and norovirus
      among Vietnamese children with acute gastroenteritis and the emergence of a novel
      norovirus GII.4 variant.
AB  - A prospective study was conducted to evaluate two immunochromatography (ICG)
      tests for detection of group A rotavirus and norovirus GII, the commercial
      Dipstick 'Eiken' Rota kit (SA Scientific, USA) and the NV IC-1 stick (Immuno
      Probe, Japan). Polymerase chain reaction (PCR) with specific primer pairs (Beg9
      and VP7-1', for group A rotavirus; COG2F and G2SKR, for norovirus GII) was used
      as the reference method. The results of ICG tests were compared with those of
      reference method. The sensitivity, specificity and agreement between ICG tests
      and PCR were 87.8%, 93.3% and 89.4%, respectively, for rotavirus ICG test; and
      73.7%, 100% and 95.2%, respectively, for norovirus ICG test. The
      immunochromatography assay for norovirus used in this study could detect not only
      common noroviruses, but also a novel norovirus GII.4 variant, which emerged in Ho
      Chi Minh City in 2006. Immunochromatography tests are easy, rapid and useful
      assays for detection of rotavirus and norovirus among pediatric patients with
      acute gastroenteritis in Vietnam.

PMID- 17496325
TI  - Two cases of subacute sclerosing panencephalitis associated with brainstem
      involvement.
AB  - The most commonly involved areas in subacute sclerosing panencephalitis (SSPE)
      are periventricular and subcortical white matter. The basal ganglia, cerebellum,
      spinal cord and corpus callosum are less commonly involved. Brainstem involvement
      is rare and usually accompanied by other intracranial lesions. In this article,
      we report two cases of SSPE associated with brainstem involvement. The first case
      a 9-year-old girl had the typical symptom of SSPE. Magnetic resonance imaging
      (MRI) of the brain revealed a focal lesion 2 x 2.5 cm a diameter in the pons. The
      second case was a 6-year-old girl. On admission, MRI of the brain was normal.
      During 6th month of follow-up, T2-weighted MRI showed a hyperintense lesion in
      the pons and pedincule of cerebellum. On account of these cases we would like to
      stress that brainstem involvement may be seen in patients with SSPE; therefore,
      these patients should be monitored for this disorder.

PMID- 17496326
TI  - Urodynamic evaluation in primary enuresis: an investigative and treatment outcome
      correlation.
AB  - A prospective study was done in pediatric out-patient department of a tertiary
      care hospital to evaluate the role of urodynamics in the management of primary
      enuresis in the 5-14-year-old children and to compare the effectiveness of
      multidimensional behavioral therapy with pharmacological therapy. Hundred and
      nineteen children between 5-14 years with primary enuresis were evaluated
      clinically and investigated. Three patients with obvious organic causes were then
      excluded. The remaining patients were given either behavioral or pharmacological
      treatment on the basis of urodynamic assessment. Urodynamic abnormalities were
      seen in 80/116 (68.9%) patients namely uninhibited bladder contraction 50/116
      (43.1%), small bladder capacity 20/116 (17.2%), large bladder capacity 4/116
      (3.4%), decreased bladder compliance 3/116 (2.5%) and detrusor sphincter
      dyssenergia 3/116 (2.5%). Combination of abnormal micturition history stating
      daytime urgency or frequency or dysfunctional voiding symptoms like squatting
      and/or abnormal voiding charts could predict abnormal results of urodynamics
      correctly with sensitivity of 81% and specificity of 86.2%. Ultrasound identified
      only 38/80 enuretics with urodynamic abnormalities although it was 100% specific.
      Additionally one patient who was identified as having a small bladder capacity on
      voiding chart was seen to have mild pelvicalyceal dilatation on ultrasound and
      subsequently on urodynamic assessment was found to have Detrusor sphincter
      dyssenergia (DSD). Behavioral therapy as compared to drug therapy produced more
      complete remission (17/18 vs. 14/18) and lesser relapse rate (2/17 vs. 5/14) in
      monosymptomatic enuretics with normal urodynamics. In patients with urodynamic
      abnormality, response rates with behavioral therapy, imipramine, oxybutynin and
      flavoxate were 73.9% (CI 56-91.8%), 89.4% (CI 75.7-100%), 94.2% (CI 84.7-100%)
      and 89.4% (CI 75.7-100%), respectively. Specific drug therapy as per the
      urodynamic abnormality was significantly more effective 49/57 [86% (CI 77-95%)]
      vs 17/23 [73.9% (CI 56.1-91.9%)] at P < 0.05 than behavioral therapy in patients
      with underlying abnormal urodynamics. Micturition history and voiding chart can
      be used as screening tool for enuretics. Behavioral therapy should be the first
      line treatment for mono symptomatic and drug therapy for polysymptomatic
      enuretics. Urodynamic testing may be reserved for polysymptomatic enuretics with
      abnormal ultrasound or those who fail to respond to first line treatment.

PMID- 17496327
TI  - Congenital nephrotic syndrome in a Nigerian infant.
AB  - Although nephrotic syndrome is common among African children, the congenital
      forms of it are rare. This report describes the clinical presentation of a 6-week
      old Nigerian infant who presented with marked pedal oedema, heavy proteinuria and
      serum hypoproteinaemia leading to the diagnosis of congenital nephrotic syndrome.
      This case is being reported to create awareness about this condition and to
      highlight diagnostic and therapeutic challenges.

PMID- 17496328
TI  - Oleamide synthesizing activity from rat kidney: identification as cytochrome c.
AB  - Oleamide (cis-9-octadecenamide) is the prototype member of an emerging class of
      lipid signaling molecules collectively known as the primary fatty acid amides.
      Current evidence suggests that oleamide participates in the biochemical
      mechanisms underlying the drive to sleep, thermoregulation, and antinociception.
      Despite the potential importance of oleamide in these physiologic processes, the
      biochemical pathway for its synthesis in vivo has not been established. We report
      here the discovery of an oleamide synthetase found in rat tissues using
      [(14)C]oleoyl-CoA and ammonium ion. Hydrogen peroxide was subsequently found to
      be a required cofactor. The enzyme displayed temperature and pH optima in the
      physiologic range, a remarkable resistance to proteolysis, and specificity for
      long-chain acyl-CoA substrates. The reaction demonstrated Michaelis-Menten
      kinetics with a K(m) for oleoyl-CoA of 21 microm. Proteomic, biochemical, and
      immunologic analyses were used to identify the source of the oleamide
      synthesizing activity as cytochrome c. This identification was based upon peptide
      mass fingerprinting of isolated synthase protein, a tight correlation between
      enzymatic activity and immunoreactivity for cytochrome c, and identical
      functional properties shared by the tissue-derived synthetase and commercially
      obtained cytochrome c. The ability of cytochrome c to catalyze the formation of
      oleamide experimentally raises the possibility that cytochrome c may mediate
      oleamide biosynthesis in vivo.

PMID- 17496329
TI  - Regulation of lipid flux between liver and adipose tissue during transient
      hepatic steatosis in carnitine-depleted rats.
AB  - Rats with carnitine deficiency due to trimethylhydrazinium propionate
      (mildronate) administered at 80 mg/100 g body weight per day for 10 days
      developed liver steatosis only upon fasting. This study aimed to determine
      whether the transient steatosis resulted from triglyceride accumulation due to
      the amount of fatty acids preserved through impaired fatty acid oxidation and/or
      from up-regulation of lipid exchange between liver and adipose tissue. In liver,
      mildronate decreased the carnitine content by approximately 13-fold and, in
      fasted rats, lowered the palmitate oxidation rate by 50% in the perfused organ,
      increased 9-fold the triglyceride content, and doubled the hepatic very low
      density lipoprotein secretion rate. Concomitantly, triglyceridemia was 13-fold
      greater than in controls. Hepatic carnitine palmitoyltransferase I activity and
      palmitate oxidation capacities measured in vitro were increased after treatment.
      Gene expression of hepatic proteins involved in fatty acid oxidation,
      triglyceride formation, and lipid uptake were all increased and were associated
      with increased hepatic free fatty acid content in treated rats. In periepididymal
      adipose tissue, mildronate markedly increased lipoprotein lipase and hormone
      sensitive lipase activities in fed and fasted rats, respectively. On refeeding,
      carnitine-depleted rats exhibited a rapid decrease in blood triglycerides and
      free fatty acids, then after approximately 2 h, a marked drop of liver
      triglycerides and a progressive decrease in liver free fatty acids. Data show
      that up-regulation of liver activities, peripheral lipolysis, and lipoprotein
      lipase activity were likely essential factors for excess fat deposit and release
      alternately occurring in liver and adipose tissue of carnitine-depleted rats
      during the fed/fasted transition.

PMID- 17496330
TI  - Eps8 facilitates cellular growth and motility of colon cancer cells by increasing
      the expression and activity of focal adhesion kinase.
AB  - In an attempt to study the role of Eps8 in human carcinogenesis, we observe that
      ectopic overexpression of Eps8 in SW480 cells (low Eps8 expression) increases
      cell proliferation. By contrast, expressing eps8 small interference RNA in SW620
      and WiDr cells (high Eps8 expression) reduces their proliferation rate.
      Interestingly, attenuation of Eps8 decreases Src Pi-Tyr-416, Shc Pi-Tyr-317, and
      serum-induced FAK Pi-Tyr-397 and Pi-Tyr-861. Remarkably, by virtue of mammalian
      target of rapamycin/STAT3 Pi-Ser-727, Eps8 modulates FAK expression required for
      cell proliferation. Within 62% of colorectal tumor specimens examined, >2-fold
      enhancement of Eps8 as compared with their normal counterparts is observed,
      especially for those from the advanced stage. In agreement with the modulation of
      FAK by Eps8, the concomitant expression of these two proteins in tumor specimens
      is observed. Notably, Eps8 attenuation also impedes the motility of SW620 and
      WiDr cells, which can be rescued by ectopically expressed FAK. This finding
      discloses the indispensability of Eps8 and FAK in cell locomotion. These results
      provide a novel mechanism for Eps8-mediated FAK expression and activation in
      colon cancer cells.

PMID- 17496331
TI  - Quantitative proteomics analysis reveals that proteins differentially expressed
      in chronic pancreatitis are also frequently involved in pancreatic cancer.
AB  - The effective treatment of pancreatic cancer relies on the diagnosis of the
      disease at an early stage, a difficult challenge. One major obstacle in the
      development of diagnostic biomarkers of early pancreatic cancer has been the dual
      expression of potential biomarkers in both chronic pancreatitis and cancer. To
      better understand the limitations of potential protein biomarkers, we used ICAT
      technology and tandem mass spectrometry-based proteomics to systematically study
      protein expression in chronic pancreatitis. Among the 116 differentially
      expressed proteins identified in chronic pancreatitis, most biological processes
      were responses to wounding and inflammation, a finding consistent with the
      underlining inflammation and tissue repair associated with chronic pancreatitis.
      Furthermore 40% of the differentially expressed proteins identified in chronic
      pancreatitis have been implicated previously in pancreatic cancer, suggesting
      some commonality in protein expression between these two diseases. Biological
      network analysis further identified c-MYC as a common prominent regulatory
      protein in pancreatic cancer and chronic pancreatitis. Lastly five proteins were
      selected for validation by Western blot and immunohistochemistry. Annexin A2 and
      insulin-like growth factor-binding protein 2 were overexpressed in cancer but not
      in chronic pancreatitis, making them promising biomarker candidates for
      pancreatic cancer. In addition, our study validated that cathepsin D, integrin
      beta1, and plasminogen were overexpressed in both pancreatic cancer and chronic
      pancreatitis. The positive involvement of these proteins in chronic pancreatitis
      and pancreatic cancer will potentially lower the specificity of these proteins as
      biomarker candidates for pancreatic cancer. Altogether our study provides some
      insights into the molecular events in chronic pancreatitis that may lead to
      diverse strategies for diagnosis and treatment of these diseases.

PMID- 17496332
TI  - Remnant-like lipoprotein particles impair endothelial function: direct and
      indirect effects on nitric oxide synthase.
AB  - Remnant-like lipoprotein particles (RLPs) have been implicated as potentially
      atherogenic lipoproteins. Endothelial dysfunction is known to be an early event
      in atherosclerosis and an important contributor to the pathogenesis of coronary
      artery disease. Moreover, there is considerable evidence linking increased RLP
      cholesterol levels with endothelial dysfunction, reflected by impaired
      endothelial vasodilatation and abnormal endothelial secretion. The underlying
      mechanisms by which RLPs may contribute to endothelial dysfunction are complex
      and have not been completely elucidated. Because the expression and activation of
      endothelial nitric oxide synthase (eNOS) are vital to endothelial function, and
      recent data have implied an association between RLPs and eNOS, this manuscript
      proposes the hypothesis that RLPs could impair endothelial function via direct
      and indirect effects on eNOS: RLPs may affect the autophosphorylation of focal
      adhesion kinase and its downstream phosphatidylinositol kinase/Akt (protein
      kinase B) signaling pathway, resulting in eNOS inactivation through induction of
      intracellular oxidative stress in endothelial cells; and RLPs could affect the
      expression or activation of eNOS indirectly by stimulating secretion of various
      inflammatory factors from multiple origins. The practical applications of this
      manuscript provide new insights for the future investigation of RLPs.

PMID- 17496333
TI  - Mapping genetic loci that regulate lipid levels in a NZB/B1NJxRF/J intercross and
      a combined intercross involving NZB/B1NJ, RF/J, MRL/MpJ, and SJL/J mouse strains.
AB  - The NZB/B1NJ (NZB) mouse strain exhibits high cholesterol and HDL levels in blood
      compared with several other strains of mice. To study the genetic regulation of
      blood lipid levels, we performed a genome-wide linkage analysis in 542 chow-fed
      F2 female mice from an NZBxRF/J (RF) intercross and in a combined data set that
      included NZBxRF and MRL/MpJxSJL/J intercrosses. In the NZBxRF F2 mice, the
      cholesterol and HDL concentrations were influenced by quantitative trait loci
      (QTL) on chromosome (Chr) 5 [logarithm of odds (LOD) 17-19; D5Mit10] that was in
      the region identified earlier in crosses involving NZB mice, but two QTLs on Chr
      12 (LOD 4.7; D12Mit182) and Chr 19 (LOD 5.7; D19Mit1) were specific to the NZBxRF
      intercross. Triglyceride levels were affected by two novel QTLs at D12Mit182 (LOD
      8.7) and D15Mit13 (LOD 3.5). The combined-cross linkage analysis (1,054 mice, 231
      markers) 1) identified four shared QTLs (Chrs 5, 7, 14, and 17) that were not
      detected in one of the parental crosses and 2) improved the resolution of two
      shared QTLs. In summary, we report additional loci regulating lipid levels in NZB
      mice that had not been identified earlier in crosses involving the NZB strain of
      mice. The identification of shared loci from multiple crosses increases
      confidence toward finding the QTL gene.

PMID- 17496334
TI  - Water-extended polyester neutron shield for a 252Cf neutron source.
AB  - A Monte Carlo study to determine the shielding features to neutrons of water
      extended polyester was carried out. During calculations, (252)Cf and shielding
      were modelled and the neutron spectra as well as the H(10) were calculated in
      four sites. The calculation was extended to include a water shielding, the source
      in vacuum and in air. Besides neutron shielding characteristics, the Kerma in air
      due to gammas emitted by (252)Cf and due to capture gamma rays in the shielding
      were included.

PMID- 17496336
TI  - Mathematical modeling of flow and kinetics in a reactor for dilute-Acid
      hydrolysis of cellulose particles: a mixture flow approach.
AB  - A mathematical model to simulate the dilute-acid hydrolysis process of cellulose
      particles is presented. In this model, the mass is treated as a mixture of
      different components. A test case is considered for which transport equations for
      components are developed and solved together with the momentum equation for the
      fluid flow. To solve the model equations, a commercially available flow solver
      was used. All input data were taken from previously published works. For the
      small static mixer considered as test geometry, the result, in terms of the
      conversion of the cellulose particles, was reasonable. With input parameters that
      are relevant to a plant-size reactor, the model can be used to predict the
      conversion of both cellulose and hemicellulose particles.

PMID- 17496337
TI  - Evaluation of kinetic parameters for enzymatic interesterification synthesis of L
      ascorbyl lactate by response surface methodology.
AB  - The kinetics of lipase-catalyzed interesterification synthesis of L-ascorbyl
      lactate was studied. To determine the enzyme kinetic constants of the
      interesterification, a three-factor and five-level central composite design was
      used. The factors studied were ethyl lactate concentration, reaction temperature
      (T), and water content (w). Moreover, a statistical approach called the response
      surface method (RSM) was used to predict the kinetic constants. Finally, the
      relationships between the kinetic constants (Vm and Km) and the reaction
      parameters (T and w) were obtained. To assess the accuracy of the RSM approach
      for determining Vm and Km, detailed validation experiments were carried out by
      the conventional approach at four different reaction parameters(35 degrees C, 10
      microL; 45 degrees C, 20 microL; 55 degrees C, 15 microL; 65 degrees C, 18
      microL). The results indicated that the RSM approach gave reasonable results for
      the determination of Vm and Km in the range of tested parameters.

PMID- 17496338
TI  - Influence of inhibitory compounds and minor sugars on xylitol production by
      Debaryomyces hansenii.
AB  - To obtain in-depth information on the overall metabolic behavior of the new good
      xylitol producer Debaryomyces hansenii UFV-170, batch bioconversions were carried
      out using semisynthetic media with compositions simulating those of typical
      acidic hemicellulose hydrolysates of sugarcane bagasse. For this purpose, we used
      media containing glucose (4.3-6.5 g/L), xylose (60.1-92.1 g/L), or arabinose (5.9
      9.2 g/L), or binary or ternary mixtures of them in either the presence or absence
      of typical inhibitors of acidic hydrolysates, such as furfural (1.0-5.0 g/L),
      hydroxymethylfurfural (0.01- 0.30 g/L), acetic acid (0.5-3.0 g/L), and vanillin
      (0.5-3.0 g/L). D. hansenii exhibited a good tolerance to high sugar
      concentrations as well as to the presence of inhibiting compounds in the
      fermentation media. It was able to produce xylitol only from xylose, arabitol
      from arabinose, and no glucitol from glucose. Arabinose metabolization was
      incomplete, while ethanol was mainly produced from glucose and, to a lesser less
      extent, from xylose and arabinose. The results suggest potential application of
      this strain in xyloseto- xylitol bioconversion from complex xylose media from
      lignocellulosic materials.

PMID- 17496339
TI  - Production of lipase by a newly isolated Bacillus coagulans under solid-state
      fermentation using melon wastes.
AB  - An extracellular lipase was produced by Bacillus coagulans by solid-state
      fermentation. Solid waste from melon was used as the basic nutrient source and
      was supplemented with olive oil. The highest lipase production (78,069 U/g) was
      achieved after 24 h of cultivation with 1% olive oil enrichment. Enzyme had an
      optimal activity at 37 degrees C and pH 7.0, and sodium dodecyl sulfate increased
      lipase activity. NH4NO3 increased enzyme production, whereas organic nitrogen had
      no effect. The effect of the type of carbon sources on lipolytic enzyme
      production was also studied. The best results were obtained with starch and
      maltose (148,932 and 141,629 U/g, respectively), whereas a rather low enzyme
      activity was found in cultures grown on glucose and galactose (approx 118,769 and
      123,622 U/g, respectively). Enzyme was inhibited with Mn+2 and Ni+2 by 68 and
      74%, respectively. By contrast, Ca+2 enhanced enzyme production by 5%.

PMID- 17496340
TI  - Influence of temperature on performance of an anaerobic sequencing biofilm batch
      reactor with circulation applied to treatment of low-strength wastewater.
AB  - The effect of temperature on the performance of an anaerobic sequencing biofilm
      batch reactor (ASBBR) with liquid-phase recirculation was assessed. Assays were
      performed using a recirculation velocity of 0.20 cm/s, 8-h cycles, and an average
      treated synthetic wastewater volume of 2 L/cycle with a concentration of 500 mg
      of Chemical Oxygen Demand (COD)/L. Operation temperatures were 15, 20, 25, 30,
      and 35 degrees C. At 25, 30, and 35 degrees C, organic matter removal
      efficiencies for filtered samples ranged from 81 to 83%. At lower temperatures,
      namely 15 and 20 degrees C, removal efficiency decreased significantly to 61 and
      65%, respectively. A first-order model could be fitted to the experimental
      concentration profile values. The first-order kinetic parameter value of this
      model varied from 0.46 to 0.81 h-1 considering the lowest and highest temperature
      studied. Moreover, analysis of the removal profile values allowed fitting of an
      Arrhenius-type equation with an activation energy of 5715 cal/mol.

PMID- 17496341
TI  - Effects of tetrazolium chloride concentration, O2, and cell age on dehydrogenase
      activity of Aspergillus niger.
AB  - The effects of triphenyl tetrazolium chloride (TTC) concentration, cell age, and
      presence of O2 on the dehydrogenase activity of Aspergillus niger as measured by
      triphenyl formazan (TF) yield were investigated. The results indicated that
      increasing TTC concentration initially increased the TF yield and then decreased
      it. The maximum TF yield was observed at a TTC concentration of 30 g/L for young
      cells (4 d old) and 20 g/L for old cells (12 d old). Conducting the test under
      anaerobic conditions increased the TF yield. About 18% of the TF produced was
      converted back into TTC in the presence of oxygen. The relationship between
      dehydrogenase activity of A. niger (as measured by TF yield) and cell mass was
      found to be linear. A kinetic model describing the relationship between reaction
      rate (micromoles of TF formed per hour) and TTC concentration while accounting
      for substrate inhibition was developed, and the model constants were calculated.
      The optimum TTCtest conditions for dehydrogenase activity measurement of A. niger
      were a TTC concentration of 20 g/L, a pH of 9.0, a temperature of 55 degrees C,
      an incubation time of 3 h, and anaerobic conditions.

PMID- 17496342
TI  - Effects of different carbon and nitrogen sources on naphthoquinone production of
      Cordyceps unilateralis BCC 1869.
AB  - The production of six naphthoquinone derivatives, erythrostominone,
      deoxyerythrostominone, 4-O-methyl erythrostominone, epierythrostominol,
      deoxyerythrostominol, and 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa- 1,3-dienyl)
      1,4-naphthoquinone, was examined during the growth of Cordyceps unilateralis BCC
      1869 on different carbon and nitrogen sources. Erythrostominone production by the
      fungus accounted for more than 50% of total naphthoquinones, but production of
      each of the other five derivatives accounted for less than 20% of total
      naphthoquinones. The highest volumetric production rate of erythrostominone and
      overall naphthoquinone production rate were obtained on mannose as a sole carbon
      source and ammonium sulfate as a sole nitrogen source (4922.4 +/- 118.8 mg/[L.d]
      and 5.03 g/[L.d], respectively). The highest growth rate was obtained on
      arabinose (0.043 h-1), whereas the maximum overall naphthoquinone concentration
      was obtained on lactose (2 g/L) at 237 h. These naphthoquinones were produced
      with no pH control and were first detected at a pH of about 3.0 to 4.0. These
      results suggest that carbon and nitrogen influenced directly the production of
      naphthoquinones.

PMID- 17496343
TI  - Decoding IgE Fc receptors.
AB  - Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic
      diseases by interacting with two membrane receptors: high-affinity FcepsilonRI
      and low-affinity FcepsilonRII (CD23). Allergeninduced IgE-occupied FcepsilonRI
      aggregation on the mast cell or basophil cell surface leads to the activation of
      intracellular signaling events and eventually the release of pre-formed and de
      novo synthesized inflammatory mediators. The role of FcepsilonRII in allergic
      diseases has been proposed to include regulation of IgE synthesis, enhanced
      histamine release from basophils, and a contribution to Ag-IgE complex
      presentation but the exact function of CD23 remains poorly understood. This
      review summarizes some new developments in IgE Fc-receptor studies with an
      emphasis on regulation of FcepsilonRI expression and signal transduction,
      including monomeric IgE, lipid raft segregation, and some recently identified
      negative regulators. A better understanding of signaling events following IgE FcR
      aggregation will shed new light on how allergy patients might be treated more
      safely and effectively.

PMID- 17496344
TI  - LIGHT-related molecular network in the regulation of innate and adaptive
      immunity.
AB  - The LIGHT-related molecular network is composed of at least seven interacting
      receptors and ligands. Recent studies reveal that this network has profound
      immune regulatory functions for both innate and adaptive immunity. Experimental
      data support the concept that this network may also play roles in the
      pathogenesis of human diseases including cancer, infection, transplantation
      tolerance, and autoimmune diseases. In this review, we attempt to dissect each
      molecular interaction in detail and assemble them in the context of their roles
      in the pathogenesis and possible therapeutic potential in human diseases.

PMID- 17496345
TI  - Mechanisms controlling production of membrane and secreted immunoglobulin during
      B cell development.
AB  - The immunoglobulin gene which encodes both membrane-associated and secreted
      proteins through alternative RNA processing reactions has been a model system
      used for over 25 yr to better understand the regulatory mechanisms governing
      alternative RNA processing. This gene contains competing cleavage-polyadenylation
      and RNA splicing reactions and the relative use of the two pathways is
      differentially regulated between B cells and plasma cells. General cleavage
      polyadenylation and RNA splicing reactions are both altered during B cell
      maturation to affect immunoglobulin expression. However, the specific factors
      involved in this regulation have yet to be identified clearly. As transcriptional
      regulators stimulate the developmental RNA processing switch, microarray analysis
      is a promising approach to identify candidate regulators of this complex RNA
      processing mechanism.

PMID- 17496346
TI  - Is the sugar always sweet in intestinal inflammation?
AB  - Immune responses are mediated mainly by protein/protein interactions. In
      addition, protein/carbohydrate (sugar) interactions through specific protein
      families termed lectin and chi-lectin are also involved in several immune and
      biological responses under not only the state of health but also inflammatory
      conditions. Interestingly, recent studies have identified unexpected roles of
      animal lectins (galectin-1 and galectin-4) and chi-lectin (chitinase 3-like-1) in
      intestinal inflammation. Galectin-1 contributes to the suppression of intestinal
      inflammation by the induction of effector T cell apoptosis. In contrast, galectin
      4 is involved in the exacerbation of this inflammation by specifically
      stimulating intestinal CD4+ T cells to produce IL-6. CHI3L1 enhances the
      host/microbial interaction that leads to the exacerbation of intestinal
      inflammation. In this review, we discuss a novel aspect of lectin/carbohydrate
      interactions in intestinal inflammation.

PMID- 17496347
TI  - Intestinal innate immunity and the pathogenesis of Salmonella enteritis.
AB  - Acute gastroenteritis caused by Salmonella typhimurium infection is a clinical
      problem with significant public health impact. The availability of several
      experimental models of this condition has allowed detailed investigation of the
      cellular and molecular interactions involved in its pathogenesis. Such studies
      have shed light on the roles played by bacterial virulence factors and host
      innate immune mechanisms in the development of intestinal inflammation.

PMID- 17496350
TI  - Diabetes research: are we doing enough?

PMID- 17496349
TI  - Diabetes in 2007--what are the promises & challenges?

PMID- 17496348
TI  - Transcription factors in the control of dendritic cell life cycle.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that guard all parts of
      the body. They have the unique ability to prime T cells and generate primary
      immune responses. Their journey beginning with the development from precursor
      cells and ending with their death is controlled by a group of transcription
      factors. Some of the transcription factors like PU.1 are involved in more than
      one stage of DC life. Other transcription factors including Ikaros and JAK3 are
      involved in the development of more than one cell type. For a long time, the
      cellular and molecular mechanisms underlying the development, differentiation,
      maturation, and other stages of DC life were not well understood. However, in
      recent years novel information has been published by many researchers to better
      understand the molecular mechanisms of the development and function of DCs in
      immunological diseases such as asthma, cancer, autoimmunity, and transplantation.
      This review will discuss the various transcription factors and signaling pathways
      involved in each stage of the life cycle of DCs.

PMID- 17496351
TI  - Health related quality of life in patients with type I diabetes mellitus: generic
      & disease-specific measurement.
AB  - BACKGROUND & OBJECTIVE: An ideal instrument for the assessment of health related
      quality of life (HRQOL) in patients with diabetes mellitus type I (T1DM) should
      incorporate the benefits of both generic and disease-specific instruments. The
      objective of this study was to investigate the responsiveness and the ability to
      provide information about diabetes-specific associations with HRQOL, of two
      generic instruments, in comparison with two diabetes-specific instruments, in
      patients with T1DM. METHODS: In a Dutch cohort of 234 patients with T1DM we
      longitudinally assessed HRQOL using both generic and diabetes-specific
      instruments. We investigated the responsiveness, the associations with diabetes
      specific variables and the identification of specific patients by the instruments
      used. RESULTS: The generic RAND-36 was able to detect statistically significant
      and clinically relevant changes in HRQOL over time. Moreover, the RAND-36 was
      associated with (changes in) diabetes-specific variables. The generic and
      diabetes-specific instruments partly identified different patients with lowest
      HRQOL. INTERPRETATION & CONCLUSION: The RAND-36 was highly responsive to changes
      in HRQOL in patients with T1DM and revealed diabetes-specific associations with
      HRQOL. A low correlation between the generic and diabetes-specific instruments
      and partly different identification of patients with lower HRQOL support the
      complementary use of these instruments in patients with T1DM.

PMID- 17496352
TI  - Epidemiology of type 2 diabetes: Indian scenario.
AB  - India leads the world with largest number of diabetic subjects earning the
      dubious distinction of being termed the "diabetes capital of the world".
      According to the Diabetes Atlas 2006 published by the International Diabetes
      Federation, the number of people with diabetes in India currently around 40.9
      million is expected to rise to 69.9 million by 2025 unless urgent preventive
      steps are taken. The so called "Asian Indian Phenotype" refers to certain unique
      clinical and biochemical abnormalities in Indians which include increased insulin
      resistance, greater abdominal adiposity i.e., higher waist circumference despite
      lower body mass index, lower adiponectin and higher high sensitive C-reactive
      protein levels. This phenotype makes Asian Indians more prone to diabetes and
      premature coronary artery disease. At least a part of this is due to genetic
      factors. However, the primary driver of the epidemic of diabetes is the rapid
      epidemiological transition associated with changes in dietary patterns and
      decreased physical activity as evident from the higher prevalence of diabetes in
      the urban population. Even though the prevalence of microvascular complications
      of diabetes like retinopathy and nephropathy are comparatively lower in Indians,
      the prevalence of premature coronary artery disease is much higher in Indians
      compared to other ethnic groups. The most disturbing trend is the shift in age of
      onset of diabetes to a younger age in the recent years. This could have long
      lasting adverse effects on nation's health and economy. Early identification of
      at-risk individuals using simple screening tools like the Indian Diabetes Risk
      Score (IDRS) and appropriate lifestyle intervention would greatly help in
      preventing or postponing the onset of diabetes and thus reducing the burden on
      the community and the nation as a whole.

PMID- 17496353
TI  - Childhood diabetes mellitus: recent advances & future prospects.
AB  - Diabetes mellitus (DM) is a metabolic disease characterized by absolute or
      relative insulin deficiency. Absolute deficiency of insulin most commonly results
      from an autoimmune destruction of insulin producing cells in the pancreas and in
      general, the term Type 1 DM (T1DM) is used to denote childhood diabetes
      associated with autoimmunity and absolute insulin deficiency. The term Type 2 DM
      (T2DM) is used to denote diabetes resulting from a relative deficiency of insulin
      when insulin secretion is inadequate to overcome co-existent resistance to
      insulin action on carbohydrate, protein or fat metabolism; T2DM is most commonly
      associated with the prototypic insulin resistant state of obesity. In the western
      hemisphere DM is one of the most prevalent chronic diseases in childhood, whereas
      the incidence of T1DM in developing countries is significantly less than that in
      the western hemisphere. Epidemiological studies indicate that there is gradual
      but steady increase in the incidence of both T1DM and T2DM in both developed and
      developing countries. This review provides an overview of the major advances in
      our understanding of the aetiology, pathogenesis, and clinical management of DM
      in children with the focus being on T1DM. Genetic predisposition, environmental
      causes, and emerging concepts of the pathogenesis of T1DM such as the accelerator
      hypothesis are discussed. The goals of treating a child with DM are to achieve
      normal growth and development with prevention of acute and chronic complications
      of DM. These goals are achieved by co-ordinated care delivered by a
      multidisciplinary team focusing on insulin administrations, glucose monitoring,
      meal planning, and screening for complications. Newer insulin analogues
      ("designer" insulin) and automated methods of delivery via programmable pumps
      have revolutionized the care of the child with diabetes. Though T1DM cannot yet
      be prevented, ongoing trials and strategies aimed at modulating the autoimmune
      response and the burgeoning science of embryonic stem cell biology, and isolating
      and propagating islet cell progenitor cells are discussed in this review.

PMID- 17496354
TI  - Ethnicity, type 2 diabetes & migrant Asian Indians.
AB  - The rapid increase of diabetes prevalence in the US population and across all
      westernized world has been associated with environmental changes that promote
      obesity. However, studies conducted in various ethnic groups within the US
      population have pointed out differences in susceptibility to diabetes within the
      same environmental pressure. Of particular interest is the growing evidence that
      Asian Indians, i.e., persons originating from the Indian Subcontinent, are at
      uniquely heightened risk for type 2 diabetes when compared to other populations.
      The elucidation of the mechanisms responsible for the heterogeneous relationship
      between obesity and type 2 diabetes in various ethnic groups, and particularly in
      Asian Indians, may give important contributions to better understand the complex
      mechanisms involved in the development of type 2 diabetes. This review examines
      epidemiological and pathophysiological aspects of the interaction between
      environment and ethnic predisposition to type 2 diabetes in Asian Indians
      migrated to the US.

PMID- 17496355
TI  - Genetic predisposition to type 2 diabetes among Asian Indians.
AB  - Genes play an important role in the development of diabetes mellitus. Type 2
      diabetes is a polygenic disorder with multiple genes located on different
      chromosomes contributing to its susceptibility. Analysis of the genetic factors
      is further complicated by the fact that numerous environmental factors interact
      with genes to produce the disorder. Only a minority of cases of type 2 diabetes
      are caused by single gene defects and one example is maturity onset diabetes of
      the young (MODY). Till date knowledge of the genetics of type 2 diabetes is
      limited. Consistent with the complex web of physiologic defects in type 2
      diabetes, the genetics of the disorder involves a large number of susceptibility
      genes, each with a relatively small effect. In this article, the studies on
      genetics of diabetes in Asian Indians are reviewed. As Asian Indians have an
      increased susceptibility to diabetes and have increased insulin resistance, they
      are a unique population for carrying out genetic studies. There appears to be
      certain genes which predispose Indians to diabetes while other genes (for example
      Pro 12 Ala polymorphism of PPAR gamma gene) which afford protection against
      diabetes and insulin resistance to Caucasians, do not appear to protect Indians.
      Further studies are needed to unravel the genetics of diabetes in South Asians .

PMID- 17496356
TI  - New frontiers in the management of type 2 diabetes.
AB  - Type 2 diabetes is a chronic, debilitating disease characterized by insulin
      resistance, impaired insulin secretion, and hyperglycaemia, and afflicting at
      least 171 million people worldwide (31.7 million in India). This chronic disease
      is not benign and patients with diabetes suffer from numerous microvascular and
      macrovascular complications which cause a lot of morbidity and mortality. Results
      from the UKPDS (United Kingdom Prospective Diabetes Study) clearly demonstrate
      that tight glucose and blood pressure control in patients with type 2 diabetes
      prevents the development of and delays the progression of microvascular
      complications and possibly macrovascular disease. In addition, results from the
      UKPDS and other studies like the Heart Protection Study (HPS) have also shown
      that treatment of concomitant risk factors like lipids and blood pressure and the
      use of aspirin have favourable effects on cardiovascular complications and
      mortality in patients with type 2 diabetes. In order to achieve glycaemic goals,
      we have several anti-hyperglycaemic agents in our therapeutic armamentarium
      today. However, despite their availability, we have not been able to achieve
      glycaemic goals in our patients with diabetes due to a variety of reasons.
      However, there appears to be hope for the future. The progress of research in all
      fields of diabetes therapeutics from diabetes treatment to continuous glucose
      monitoring systems to novel insulin delivery systems has been spectacular. These
      advances have resulted in newer pharmacologic agents, implantable glucose sensors
      and inhaled insulin. There is also hope that large scale implementation of
      intensive lifestyle programmes and education efforts may help to prevent diabetes
      in high risk individuals. Indeed, the repertoire of options and strategies
      currently available (and in the pipeline) to treat and prevent/delay diabetes and
      its complications is impressive. In this review, we will discuss the evolving
      cardiovascular benefits of the thiazolidinediones (TZDs); describe in detail the
      newer glucose lowering gut hormones with novel mechanisms of action; delineate
      the recent advances in non invasive insulin delivery systems (including inhaled
      insulin); review the ongoing developments in continuous glucose measuring devices
      and finally present an update on the prevention of diabetes.

PMID- 17496357
TI  - Diabetic retinopathy: an Indian perspective.
AB  - Diabetic retinopathy (DR) can be defined as damage to microvascular system in the
      retina due to prolonged hyperglycaemia. The prevalence of DR in the Chennai Urban
      Rural Epidemiology (CURES) Eye Study in south India was 17.6 per cent,
      significantly lower than age-matched western counterparts. However, due to the
      large number of diabetic subjects, DR is likely to pose a public health burden in
      India. CURES Eye study showed that the major systemic risk factors for onset and
      progression of DR are duration of diabetes, degree of glycaemic control and
      hyperlipidaemia. Hypertension did not play a major role in this cross-sectional
      analysis. The role of oxidative stress, atherosclerotic end points and genetic
      factors in susceptibility to DR has been studied. It was found that DR was
      associated with increased intima-media thickness and arterial stiffness in type 2
      Indian diabetic subjects suggesting that common pathogenic mechanisms might
      predispose to diabetic microangiopathy. Curcumin, an active ingredient of
      turmeric, has been shown to inhibit proliferation of retinal endothelial cells in
      vivo. Visual disability from DR is largely preventable if managed with timely
      intervention by laser. It has been clearly demonstrated that in type 2 south
      Indian diabetic patients with proliferative DR who underwent Pan retinal
      photocoagulation, 73 per cent eyes with good visual acuity (6/9) at baseline
      maintained the same vision at 1 yr follow up. There is evidence that DR begins to
      develop years before the clinical diagnosis of type 2 diabetes. Our earlier study
      demonstrated that DR is present in 7 per cent of newly diagnosed subjects, hence
      routine retinal screening for DR even at the time of diagnosis of type 2 diabetes
      may help in optimized laser therapy. Annual retinal examination and early
      detection of DR can considerably reduce the risk of visual loss in diabetic
      individuals.

PMID- 17496358
TI  - Psychiatric co-morbidity & diabetes.
AB  - Diabetes mellitus as well as psychiatric disorders are common. These may occur
      with one another and/or one may worsen the other. Psychological stress may follow
      screening for diabetes, as well as when diabetes is first identified. Acting
      through the hypothalamo-pituitary-adrenal axis, stress may initiate or worsen
      hyperglycaemia. Depression may be a risk factor for the development of diabetes;
      it also commonly occurs in subjects with diabetes. Identification and management
      are both important in preventing the disability. A variety of antipsychotic
      medications, especially the newer agents can induce weight gain, dyslipidaemia,
      insulin resistance and diabetes. Therefore in choosing a drug, one must consider
      the risk factors and screen for metabolic syndrome. Subjects with type 1 diabetes
      can have cognitive dysfunction, eating disorders and developmental disturbances.
      Physicians caring for people with diabetes must be trained to recognize and
      manage co-morbid psychiatric conditions that commonly occur. A biopsychosocial
      disease model for both conditions can leverage the social strengths and medical
      knowledge in developing countries.

PMID- 17496359
TI  - Biomarkers of susceptibility to type 1 diabetes with special reference to the
      Indian population.
AB  - Type 1 diabetes (T1D) is a polygenic autoimmune disease. Susceptibility to T1D is
      strongly linked to a major genetic locus that is the major histocompatibility
      complex (MHC) and several other minor loci including insulin, CTLA4 that
      contribute to diabetes risk in an epistatic way. MHC harbours genes whose primary
      function is to govern immune responsiveness. Being the most polymorphic genomic
      region known in humans, MHC serves as a very exciting minigenome model for
      studying susceptibility to T1D. We have observed enormous diversity in HLA class
      I and class II genes in the north Indian population and identified several 'novel
      alleles' and 'unique haplotypes'. For example, multiple DR3+ve autoimmunity
      favouring haplotypes have been identified, some of which are unique to the Asian
      north Indian T1D patients. Our molecular studies have revealed that (i) the
      classical Caucasian autoimmunity favouring AH8.1 (HLA-A1 B8 DR3) is rare in the
      Indian population and has been replaced by a variant AH8.1v that differs from the
      Caucasian AH8.1 at several gene loci, (ii) AH8.2 (HLA-A26 B8 DR3) is the most
      common DR3 positive haplotype in this population and resembles the Indian AH8.1v
      rather than Caucasian AH8.1, and (iii) there are additional HLA-DR3 haplotypes
      HLA-A24 B8 DR3 (AH8.3), A3 B8 DR3 (AH8.4) and A31 B8 DR 3 (AH 8.5) that occur in
      the Indian population. The studies have led to a hypothesis that AH8.1 and AH8.1v
      might have co-evolved from a common ancestor but preferential divergence of AH8.2
      over AH8.1 leading to survival advantage might have been driven by vigorous
      pathogenic challenges encountered by the Indian population. These studies have
      important implications in our understanding of disease pathogenesis,
      identification of high risk individuals, disease diagnosis, disease management
      and immunological therapeutic approaches.

PMID- 17496360
TI  - The metabolic syndrome in South Asians: continuing escalation & possible
      solutions.
AB  - The metabolic syndrome is a crucial factor in causation of type 2 diabetes
      mellitus (T2DM) and coronary heart disease (CHD) in South Asians. Approximately
      20-25 per cent of urban South Asians have evidence of the metabolic syndrome.
      Furthermore, insulin resistance was reported to be present in nearly 30 per cent
      of children and adolescents in India, more so in girls. At the same time many
      young individuals have clustering of other risk factors/conditions related to
      insulin resistance (e.g., non-alcoholic fatty liver disease, obstructive sleep
      apnoea, etc.). Rapid nutritional and lifestyle transition in urbanized areas in
      various countries in South Asia are prime reasons for increasing prevalence of
      obesity and the metabolic syndrome. It is particularly important to effectively
      implement and strengthen population-based primary prevention strategies for the
      prevention of 'epidemic' of obesity and the metabolic syndrome. The lifestyle
      factor modification to prevent the metabolic syndrome and T2DM in South Asians
      should start in early childhood. Finally, there is an urgent need to conduct
      research studies regarding the correct definitions of the metabolic syndrome and
      genetic and perinatal factors related to insulin resistance in South Asians.

PMID- 17496361
TI  - Antioxidants: do they have a role in the treatment of insulin resistance?
AB  - Insulin resistance, defined as an attenuated or inadequate response to a given
      amount of insulin, is associated with a wide variety of conditions including
      obesity, type 2 diabetes, essential hypertension, cardiovascular disease,
      polycystic ovary syndrome, non-alcoholic fatty liver, breast cancer, and acquired
      immune deficiency syndrome. Although pharmacological options for the management
      of insulin resistance and type 2 diabetes have been increasing, not all patients
      benefit, as the cost of prescription medications is often beyond the financial
      capacity of many patients. A potential new approach is the use of antioxidants.
      The objectives of this review are to discuss the scientific rationale for
      proposing the evaluation of antioxidants for insulin resistance, and to provide
      an update of intervention studies, with an emphasis on clinical trials, in which
      antioxidants have been tested. Briefly, this approach capitalizes on emerging
      data implicating lipid oversupply, chronic, lowgrade inflammation, and oxidative
      stress as root causes in the development and exacerbation of insulin resistance.

PMID- 17496362
TI  - GLUT4's itinerary in health & disease.
AB  - Following the discovery of insulin 85 yr ago and the realization thereafter that
      in some individuals, tissues lose their responsiveness to this hormone, an
      enormous world-wide effort began to dissect the cellular mechanisms of insulin
      action and define abnormalities in the insulin-resistant state. A clear goal
      through the years has been to unravel the insulin signal transduction network
      regulating glucose transport. This line of investigation has provided tremendous
      insight into the physiology and pathophysiology surrounding the cellular
      processes controlled by insulin. Between the plasma membrane insulin receptor and
      the intracellularly sequestered insulin-responsive glucose transporter GLUT4,
      many events participate in the transduction of the insulin signal. In this
      review, we detail our current state of knowledge on the intricate insulin
      signaling network responsible for glucose transport in peripheral adipose and
      skeletal muscle tissues. In particular, we identify signaling connections
      spanning the insulin receptor and GLUT4. In addition, we discuss cytoskeletal
      mechanics and membrane docking and fusion mechanisms pertinently involved in the
      cellular redistribution of GLUT4 to the plasma membrane. On the whole, this
      review highlights the considerable progress in our understanding of insulin
      signaling in health and disease as we rapidly approach the centennial anniversary
      of insulin's discovery.

PMID- 17496363
TI  - The role of AMP kinase in diabetes.
AB  - Type 2 diabetes is characterized by abnormal metabolism of glucose and fat, due
      in part to resistance to the actions of insulin in peripheral tissues. If
      untreated it leads to several complications such as blindness, kidney failure,
      neuropathy and amputations. The benefit of exercise in diabetic patients is well
      known and recent research indicates that AMP activated protein kinase (AMPK)
      plays a major role in this exercise related effect. AMPK is considered as a
      master switch regulating glucose and lipid metabolism. The AMPK is an enzyme that
      works as a fuel gauge, being activated in conditions of high energy phosphate
      depletion. AMPK is also activated robustly by skeletal muscle contraction and
      myocardial ischaemia, and is involved in the stimulation of glucose transport and
      fatty acid oxidation produced by these stimuli. In liver, activation of AMPK
      results in enhanced fatty acid oxidation and decreased production of glucose,
      cholesterol, and triglycerides. The two leading diabetic drugs namely, metformin
      and rosiglitazone, show their metabolic effects partially through AMPK. These
      data, along with evidence from studies showing that chemical activation of AMPK
      in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood
      glucose concentrations and lipid profiles, make this enzyme an attractive
      pharmacological target for the treatment of type 2 diabetes and other metabolic
      disorders.

PMID- 17496364
TI  - Skeletal muscle mitochondrial dysfunction & diabetes.
AB  - Skeletal muscle insulin resistance is a key contributor to the pathophysiology of
      type 2 diabetes. Recent studies have shown that insulin resistance in a variety
      of conditions including type 2 diabetes, ageing and in offspring of type 2
      diabetes is associated with muscle mitochondrial dysfunction. The important
      question is whether insulin resistance results from muscle mitochondrial
      dysfunction or vise versa. Gene array studies from muscle biopsy samples showed
      that transcript levels of several genes, especially OXPHOS genes are altered in
      type 2 diabetic patients during poor glycaemic control but many of these
      alterations are normalized by insulin treatment suggesting that reduced insulin
      action is a factor involved in muscle mitochondrial dysfunction. Moreover,
      insulin infusion while maintaining glucose and amino acid levels results in
      increase in muscle mitochondrial gene transcript levels and ATP production
      indicating that insulin is a key regulator of muscle mitochondrial biogenesis. At
      a similar post-absorptive insulin levels both type 2 diabetic patients and non
      diabetic controls have similar muscle mitochondrial ATP production but increasing
      insulin from low to high levels stimulate ATP production only in non diabetic
      people but not in the diabetic people. The lack of muscle mitochondrial response
      to insulin in type 2 diabetic patients is likely to be related to insulin
      resistance and reduced substrate utilization.

PMID- 17496365
TI  - Endoplasmic reticulum (ER) stress & diabetes.
AB  - The endoplasmic reticulum (ER) is a central organelle entrusted with lipid
      synthesis, protein folding and protein maturation. It is endowed with a quality
      control system that facilitates the recognition and targeting of aberrant
      proteins for degradation. When the capacity of this quality control system is
      exceeded, a stress response (ER stress) is switched on. Prolonged stress leads to
      apoptosis and may thus be an important factor in the pathogenesis of many
      diseases. A complex homeostatic signaling pathway, known as the unfolded protein
      response (UPR), has evolved to maintain a balance between the load of newly
      synthesized proteins and the capacity of the ER to aid in their maturation.
      Dysfunction of the UPR plays an important role in certain diseases, especially
      those involving tissues dedicated to extracellular protein synthesis. Diabetes is
      an example of such a disease, since pancreatic beta-cells depend on efficient UPR
      signaling to meet the demands for constantly varying levels of insulin synthesis.
      Recent studies have indicated that the importance of the UPR in diabetes is not
      restricted to the beta-cell but also to tissues of peripheral insulin resistance
      such as liver and adipose tissue. Better understanding of the basic mechanisms of
      ER stress and development of insulin resistance/type 2 diabetes is pivotal for
      the identification of newer molecular targets for therapeutic interventions.

PMID- 17496366
TI  - Isolated islets in diabetes research.
AB  - This review highlights some recent developments and diversified applications of
      islets in diabetes research as they are rapidly emerging as a model system in
      biomedical and biotechnological research. Isolated islets have formed an
      effective in vitro model in antidiabetic drug development programme, screening of
      potential hypoglycaemic agents and for investigating their mechanisms of action.
      Yet another application of isolated islets could be to understand the mechanisms
      of beta cell death in vitro and to identify the sites of intervention for
      possible cytoprotection. Advances in immunoisolation and immunomodulation
      protocols have made xeno-transplantation feasible without immunosuppression thus
      increasing the availability of islets. Research in the areas of pancreatic and
      non pancreatic stem cells has given new hope to diabetic subjects to renew their
      islet cell mass for the possible cure of diabetes. Investigations of the factors
      leading to differentiation of pancreatic stem/progenitor cells would be of
      interest as they are likely to induce pancreatic regeneration in diabetics.
      Similarly search for the beta cell protective agents has a great future in
      preservation of residual beta cell mass left after diabetogenic insults. We have
      detailed various applications of islets in diabetes research in context of their
      current status, progress and future challenges and long term prospects for a
      cure.

PMID- 17496367
TI  - Telomere shortening & metabolic/vascular diseases.
AB  - Telomeres are specialized DNA-protein structures located at the ends of
      eukaryotic chromosomes whose length is progressively reduced in most somatic
      cells during ageing. Over the past decade, emerging evidence has shown that the
      telomeres are essential regulators of cellular life span and chromosome integrity
      in a dynamic fashion. By inducing genomic instability, replicative senescence and
      apoptosis, shortening of telomeres is thought to contribute to organismal ageing.
      While the aetiology of cardiovascular diseases and diabetes represent a complex
      interaction between various risk factors overlaid on different genetic
      backgrounds, the conventional risk factors often did not explain the inter
      individual variability related to predisposition of disease states. This
      underscores the need for biological indicators of ageing in evaluating the
      aetiology of several age-related disorders, and recent studies indicate that
      telomere length could qualify as an ideal marker of biological ageing. Short
      telomeres have been detected in senescent endothelial cells and vascular smooth
      muscle cells from human atherosclerotic plaque as well as in myocardial tissue
      from patients with end-stage heart failure and cardiac hypertrophy. In addition,
      telomere shortening has been demonstrated in WBCs from patients with coronary
      heart disease, premature myocardial infarction, hypertension and diabetes
      mellitus. In this review, we discuss the telomere hypothesis of ageing as well as
      human studies that address the role of telomeres in cardiovascular, diabetes and
      other cardio-metabolic pathologies.

PMID- 17496368
TI  - Animal models in type 2 diabetes research: an overview.
AB  - Type 2 diabetes is a complex and heterogeneous disorder presently affecting more
      than 100 million people worldwide and causing serious socio-economic problems.
      Appropriate experimental models are essential tools for understanding the
      pathogenesis, complications, and genetic or environmental influences that
      increase the risks of type 2 diabetes and testing of various therapeutic agents.
      The animal models of type 2 diabetes can be obtained either spontaneously or
      induced by chemicals or dietary or surgical manipulations and/or by combination
      thereof. In recent years, large number of new genetically modified animal models
      including transgenic, generalized knock-out and tissue-specific knockout mice
      have been engineered for the study of diabetes. This review gives an overview on
      the animal models of type 2 diabetes with reference to their origin/source,
      characteristic features, underlying causes/mechanism(s), advantages and
      disadvantages to the investigators in diabetes research. In addition, it
      especially describes the appropriate selection and usefulness of different animal
      models in preclinical testing of various new chemical entities (NCEs) for the
      treatment of type 2 diabetes.

PMID- 17496369
TI  - Economic analysis of diabetes care.
AB  - Many socio-economic factors and health care system related issues impact the
      outcome of diabetes and consequently its costs and vice versa. Factors that
      influence delay in diagnosis also determine complication rates and thus costs.
      Presence and severity of complications as well as co-morbid conditions are the
      most important determinants of treatment and monitoring regimen as well as the
      need for hospitalization and are therefore important factors related to costs.
      The average annual direct costs of hospitalized patients are more than double to
      those not hospitalized. Complications are also responsible for indirect costs in
      terms of productivity loss and absenteeism. Our studies show that the cost of
      providing routine care is only a fraction of the overall costs and is perhaps
      still manageable; however when this is not available or its quality is poor the
      overall direct and indirect costs, escalate with disastrous health and economic
      consequences to the individual, his family and society. Effective intervention
      means prevention both primary (health promotion and awareness) as well as
      secondary prevention (reducing the burden of complications by early diagnosis and
      effective care). Everyone involved in diabetes care need to be aware of what
      drives cost: proper effective treatment of diabetes is not but not treating
      diabetes or treating it ineffectively is very costly.

PMID- 17496370
TI  - Diabetes research in India--a citation profile.

PMID- 17496371
TI  - Active shape models with invariant optimal features: application to facial
      analysis.
AB  - This work is framed in the field of statistical face analysis. In particular, the
      problem of accurate segmentation of prominent features of the face in frontal
      view images is addressed. We propose a method that generalizes linear Active
      Shape Models (ASMs), which have already been used for this task. The technique is
      built upon the development of a nonlinear intensity model, incorporating a
      reduced set of differential invariant features as local image descriptors. These
      features are invariant to rigid transformations, and a subset of them is chosen
      by Sequential Feature Selection for each landmark and resolution level. The new
      approach overcomes the unimodality and Gaussianity assumptions of classical ASMs
      regarding the distribution of the intensity values across the training set. Our
      methodology has demonstrated a significant improvement in segmentation precision
      as compared to the linear ASM and Optimal Features ASM (a nonlinear extension of
      the pioneer algorithm) in the tests performed on AR, XM2VTS, and EQUINOX
      databases.

PMID- 17496372
TI  - Value-directed human behavior analysis from video using partially observable
      Markov decision processes.
AB  - This paper presents a method for learning decision theoretic models of human
      behaviors from video data. Our system learns relationships between the movements
      of a person, the context in which they are acting, and a utility function. This
      learning makes explicit that the meaning of a behavior to an observer is
      contained in its relationship to actions and outcomes. An agent wishing to
      capitalize on these relationships must learn to distinguish the behaviors
      according to how they help the agent to maximize utility. The model we use is a
      partially observable Markov decision process, or POMDP. The video observations
      are integrated into the POMDP using a dynamic Bayesian network that creates
      spatial and temporal abstractions amenable to decision making at the high level.
      The parameters of the model are learned from training data using an a posteriori
      constrained optimization technique based on the expectation-maximization
      algorithm. The system automatically discovers classes of behaviors and determines
      which are important for choosing actions that optimize over the utility of
      possible outcomes. This type of learning obviates the need for labeled data from
      expert knowledge about which behaviors are significant and removes bias about
      what behaviors may be useful to recognize in a particular situation. We show
      results in three interactions: a single player imitation game, a gestural robotic
      control problem, and a card game played by two people.

PMID- 17496373
TI  - Learning and removing cast shadows through a multidistribution approach.
AB  - Moving cast shadows are a major concern for foreground detection algorithms. The
      processing of foreground images in surveillance applications typically requires
      that such shadows be identified and removed from the detected foreground. This
      paper presents a novel pixel-based statistical approach to model moving cast
      shadows of nonuniform and varying intensity. This approach uses the Gaussian
      mixture model (GMM) learning ability to build statistical models describing
      moving cast shadows on surfaces. This statistical modeling can deal with scenes
      with complex and time-varying illumination, including light saturated areas, and
      prevent false detection in regions where shadows cannot be detected. The proposed
      approach can be used with pixel-based descriptions of shadowed surfaces found in
      the literature. It significantly reduces their false detection rate without
      increasing the missed detection rate. Results obtained with different scene types
      and shadow models show the robustness of the approach.

PMID- 17496374
TI  - Robust image segmentation using resampling and shape constraints.
AB  - Automated segmentation of images has been considered an important intermediate
      processing task to extract semantic meaning from pixels. We propose an integrated
      approach for image segmentation based on a generative clustering model combined
      with coarse shape information and robust parameter estimation. The sensitivity of
      segmentation solutions to image variations is measured by image resampling. Shape
      information is included in the inference process to guide ambiguous groupings of
      color and texture features. Shape and similarity-based grouping information is
      combined into a semantic likelihood map in the framework of Bayesian statistics.
      Experimental evidence shows that semantically meaningful segments are inferred
      even when image data alone gives rise to ambiguous segmentations.

PMID- 17496375
TI  - A linear programming approach to max-sum problem: a review.
AB  - The max-sum labeling problem, defined as maximizing a sum of binary (i.e.,
      pairwise) functions of discrete variables, is a general NP-hard optimization
      problem with many applications, such as computing the MAP configuration of a
      Markov random field. We review a not widely known approach to the problem,
      developed by Ukrainian researchers Schlesinger et al. in 1976, and show how it
      contributes to recent results, most importantly, those on the convex combination
      of trees and tree-reweighted max-product. In particular, we review Schlesinger et
      al.'s upper bound on the max-sum criterion, its minimization by equivalent
      transformations, its relation to the constraint satisfaction problem, the fact
      that this minimization is dual to a linear programming relaxation of the original
      problem, and the three kinds of consistency necessary for optimality of the upper
      bound. We revisit problems with Boolean variables and supermodular problems. We
      describe two algorithms for decreasing the upper bound. We present an example
      application for structural image analysis.

PMID- 17496376
TI  - Algorithmic differentiation: application to variational problems in computer
      vision.
AB  - Many vision problems can be formulated as minimization of appropriate energy
      functionals. These energy functionals are usually minimized, based on the
      calculus of variations (Euler-Lagrange equation). Once the Euler-Lagrange
      equation has been determined, it needs to be discretized in order to implement it
      on a digital computer. This is not a trivial task and, is moreover, error-prone.
      In this paper, we propose a flexible alternative. We discretize the energy
      functional and, subsequently, apply the mathematical concept of algorithmic
      differentiation to directly derive algorithms that implement the energy
      functional's derivatives. This approach has several advantages: First, the
      computed derivatives are exact with respect to the implementation of the energy
      functional. Second, it is basically straightforward to compute second-order
      derivatives and, thus, the Hessian matrix of the energy functional. Third,
      algorithmic differentiation is a process which can be automated. We demonstrate
      this novel approach on three representative vision problems (namely, denoising,
      segmentation, and stereo) and show that state-of-the-art results are obtained
      with little effort.

PMID- 17496377
TI  - Weighted minimal hypersurface reconstruction.
AB  - Many problems in computer vision can be formulated as a minimization problem for
      an energy functional. If this functional is given as an integral of a scalar
      valued weight function over an unknown hypersurface, then the sought-after
      minimal surface can be determined as a solution of the functional's Euler
      Lagrange equation. This paper deals with a general class of weight functions that
      may depend on surface point coordinates as well as surface orientation. We derive
      the Euler-Lagrange equation in arbitrary dimensional space without the need for
      any surface parameterization, generalizing existing proofs. Our work opens up the
      possibility of solving problems involving minimal hypersurfaces in a dimension
      higher than three, which were previously impossible to solve in practice. We also
      introduce two applications of our new framework: We show how to reconstruct
      temporally coherent geometry from multiple video streams, and we use the same
      framework for the volumetric reconstruction of refractive and transparent natural
      phenomena, here bodies of flowing water.

PMID- 17496378
TI  - Conformal geometry and its applications on 3D shape matching, recognition, and
      stitching.
AB  - Three-dimensional shape matching is a fundamental issue in computer vision with
      many applications such as shape registration, 3D object recognition, and
      classification. However, shape matching with noise, occlusion, and clutter is a
      challenging problem. In this paper, we analyze a family of quasi-conformal maps
      including harmonic maps, conformal maps, and least-squares conformal maps with
      regards to 3D shape matching. As a result, we propose a novel and computationally
      efficient shape matching framework by using least-squares conformal maps.
      According to conformal geometry theory, each 3D surface with disk topology can be
      mapped to a 2D domain through a global optimization and the resulting map is a
      diffeomorphism, i.e., one-to-one and onto. This allows us to simplify the 3D
      shape-matching problem to a 2D image-matching problem, by comparing the resulting
      2D parametric maps, which are stable, insensitive to resolution changes and
      robust to occlusion, and noise. Therefore, highly accurate and efficient 3D shape
      matching algorithms can be achieved by using the above three parametric maps.
      Finally, the robustness of least-squares conformal maps is evaluated and analyzed
      comprehensively in 3D shape matching with occlusion, noise, and resolution
      variation. In order to further demonstrate the performance of our proposed
      method, we also conduct a series of experiments on two computer vision
      applications, i.e., 3D face recognition and 3D nonrigid surface alignment and
      stitching.

PMID- 17496379
TI  - An approximate and efficient method for optimal rotation alignment of 3D models.
AB  - In many shape analysis applications, the ability to find the best rotation that
      aligns two models is an essential first step in the analysis process. In the
      past, methods for model alignment have either used normalization techniques, such
      as PCA alignment, or have performed an exhaustive search over the space of
      rotation to find the best optimal alignment. While normalization techniques have
      the advantage of efficiency, providing a quick method for registering two shapes,
      they are often imprecise and can give rise to poor alignments. Conversely,
      exhaustive search is guaranteed to provide the correct answer, but, even using
      efficient signal processing techniques, this type of approach can be
      prohibitively slow. In this paper, we present a new method for aligning two 3D
      shapes. We show that the method is markedly faster than existing approaches based
      on efficient signal processing and we provide registration results demonstrating
      that the alignments obtained using our method have a high degree of precision and
      are markedly better than those obtained using normalization.

PMID- 17496380
TI  - A two-level generative model for cloth representation and shape from shading.
AB  - In this paper, we present a two-level generative model for representing the
      images and surface depth maps of drapery and clothes. The upper level consists of
      a number of folds which will generate the high contrast (ridge) areas with a
      dictionary of shading primitives (for 2D images) and fold primitives (for 3D
      depth maps). These primitives are represented in parametric forms and are learned
      in a supervised learning phase using 3D surfaces of clothes acquired through
      photometric stereo. The lower level consists of the remaining flat areas which
      fill between the folds with a smoothness prior (Markov random field). We show
      that the classical ill-posed problem-shape from shading (SFS) can be much
      improved by this two-level model for its reduced dimensionality and incorporation
      of middle-level visual knowledge, i.e., the dictionary of primitives. Given an
      input image, we first infer the folds and compute a sketch graph using a sketch
      pursuit algorithm as in the primal sketch [10], [11]. The 3D folds are estimated
      by parameter fitting using the fold dictionary and they form the "skeleton" of
      the drapery/cloth surfaces. Then, the lower level is computed by conventional SFS
      method using the fold areas as boundary conditions. The two levels interact at
      the final stage by optimizing a joint Bayesian posterior probability on the depth
      map. We show a number of experiments which demonstrate more robust results in
      comparison with state-of-the-art work. In a broader scope, our representation can
      be viewed as a two-level inhomogeneous MRF model which is applicable to general
      shape-from-X problems. Our study is an attempt to revisit Marr's idea [23] of
      computing the 2(1/2)D sketch from primal sketch. In a companion paper [2], we
      study shape from stereo based on a similar two-level generative sketch
      representation.

PMID- 17496381
TI  - Extraction and analysis of multiple periodic motions in video sequences.
AB  - The analysis of periodic or repetitive motions is useful in many applications,
      such as the recognition and classification of human and animal activities.
      Existing methods for the analysis of periodic motions first extract motion
      trajectories using spatial information and then determine if they are periodic.
      These approaches are mostly based on feature matching or spatial correlation,
      which are often infeasible, unreliable, or computationally demanding. In this
      paper, we present a new approach, based on the time-frequency analysis of the
      video sequence as a whole. Multiple periodic trajectories are extracted and their
      periods are estimated simultaneously. The objects that are moving in a periodic
      manner are extracted using the spatial domain information. Experiments with
      synthetic and real sequences display the capabilities of this approach.

PMID- 17496382
TI  - On the dimensionality of face space.
AB  - The dimensionality of face space is measured objectively in a psychophysical
      study. Within this framework, we obtain a measurement of the dimension for the
      human visual system. Using an eigenface basis, evidence is presented that
      talented human observers are able to identify familiar faces that lie in a space
      of roughly 100 dimensions and the average observer requires a space of between
      100 and 200 dimensions. This is below most current estimates. It is further
      argued that these estimates give an upper bound for face space dimension and this
      might be lowered by better constructed "eigenfaces" and by talented observers.

PMID- 17496383
TI  - Multiple collaborative kernel tracking.
AB  - Those motion parameters that cannot be recovered from image measurements are
      unobservable in the visual dynamic system. This paper studies this important
      issue of singularity in the context of kernel-based tracking and presents a novel
      approach that is based on a motion field representation which employs redundant
      but sparsely correlated local motion parameters instead of compact but
      uncorrelated global ones. This approach makes it easy to design fully observable
      kernel-based motion estimators. This paper shows that these high-dimensional
      motion fields can be estimated efficiently by the collaboration among a set of
      simpler local kernel-based motion estimators, which makes the new approach very
      practical.

PMID- 17496384
TI  - Minimizing nonsubmodular functions with graph cuts - a review.
AB  - Optimization techniques based on graph cuts have become a standard tool for many
      vision applications. These techniques allow to minimize efficiently certain
      energy functions corresponding to pairwise Markov Random Fields (MRFs).
      Currently, there is an accepted view within the computer vision community that
      graph cuts can only be used for optimizing a limited class of MRF energies (e.g.,
      submodular functions). In this survey, we review some results that show that
      graph cuts can be applied to a much larger class of energy functions (in
      particular, nonsubmodular functions). While these results are well-known in the
      optimization community, to our knowledge they were not used in the context of
      computer vision and MRF optimization. We demonstrate the relevance of these
      results to vision on the problem of binary texture restoration.

PMID- 17496385
TI  - Analytical results on style-constrained bayesian classification of pattern
      fields.
AB  - We formalize the notion of style context, which accounts for the increased
      accuracy of the field classifiers reported in this journal recently. We argue
      that style context forms the basis of all order-independent field classification
      schemes. We distinguish between intraclass style, which underlies most adaptive
      classifiers, and interclass style, which is a manifestation of interpattern
      dependence between the features of the patterns of a field. We show how style
      constrained classifiers can be optimized either for field error (useful for short
      fields like zip codes) or for singlet error (for long fields, like business
      letters). We derive bounds on the reduction of error rate with field length and
      show that the error rate of the optimal style-constrained field classifier
      converges asymptotically to the error rate of a style-aware Bayesian singlet
      classifier.

PMID- 17496386
TI  - Snapshots: a novel local surface descriptor and matching algorithm for robust 3D
      surface alignment.
AB  - In this paper, a novel local surface descriptor is proposed and applied to the
      problem of aligning partial views of a 3D object. The descriptor is based on
      taking "snapshots" of the surface over each point using a virtual camera oriented
      perpendicularly to the surface. This representation has the advantage of imposing
      minimal loss of information be robust to self-occlusions and also be very
      efficient to compute. Then, we describe an efficient search technique to deal
      with the rotation ambiguity of our representation and experimentally demonstrate
      the benefits of our approaches which are pronounced especially when we align
      views with small overlap.

PMID- 17496387
TI  - Distinct multicolored region descriptors for object recognition.
AB  - The problem of object recognition has been considered here. Color descriptions
      from distinct regions covering multiple segments are considered for object
      representation. Distinct multicolored regions are detected using edge maps and
      clustering. Performance of the proposed methodologies has been evaluated on three
      data sets and the results are found to be better than existing methods when a
      small number of training views is considered.

PMID- 17496389
TI  - Toll-like receptors and glomerulonephritis.

PMID- 17496388
TI  - Childhood Henoch Schonlein purpura in Middle East countries.
AB  - HSP is the most common systemic vasculitis in children that is characterized by
      small vessel leukocytoclastic vasculitis. However, it is a self limiting disease,
      with few documented cases in Middle Eastern countries. Classic symptoms of the
      disease have been established in the literature, but new clinical features have
      recently been reported from Middle Eastern countries which include penile
      swelling, temperomandibular joint involvement, skin rash over the flexor surfaces
      of the extremities and pleural hemorrhagic effusion. Familial Mediterranean fever
      (FMF) may present as HSP. The prevalence of the FMF gene in Middle Eastern
      countries raises interesting questions regarding the use of colchicine in HSP
      patients.

PMID- 17496390
TI  - Evaluation of insulin like growth factor-1 (IGF-1) in children with different
      stages of chronic renal failure.
AB  - Growth retardation in children with chronic kidney disease (CKD) is
      multifactorial that include inadequate protein and calorie intake, persistent
      metabolic acidosis, calcitriol deficiency, renal osteodystrophy, drug toxicity,
      uremic toxins and growth factor abnormalities such as insulin-like growth factor
      (IGF) and IGF binding proteins. In this study, we compare the IGF-1 levels in
      normal and growth retarded CKD children. Serum IGF-1 levels were determined in 22
      children with end-stage renal disease, 26 children with CKD at different stages,
      23 children with normal height and weight for age and 23 children with
      constitutionally short stature. Mean serum levels of IGF-1 were 209 +/- 141 ng/ml
      in the ESRD group (group 1), 159 +/- 163 ng/ml in the CKD group (group 2), 420 +/
      182 ng/ml in normal children (group 3) and 360 +/- 183 ng/ml in children with
      constitutional short stature (group 4). The differences in the levels of IGF-1 in
      groups 1 and 2 were statistically significant when compared to groups 3 and 4 (p<
      0.0001 and p< 0.02, respectively), while the levels of IGF-1 were not
      statistically different between groups 1 and 2. No correlation was found between
      IGF-1 levels and glomerular filtration rate, height or weight in groups 1 and 2.
      In conclusion, serum levels of IGF-1 in children with CKD are significantly lower
      than healthy children.

PMID- 17496391
TI  - Successful kidney transplantation does not reverse the coagulopathy in patients
      with chronic renal failure on either hemo or peritoneal dialysis.
AB  - There is wide disagreement about the measurement of various hemostatic parameters
      in patients with chronic renal failure (CRF) concerning treatment with either
      hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). This study
      aims to characterize the coagulopathy in patients with CRF both before initiating
      dialysis, when the patients are expected to have a steady hemostatic state and
      after starting regular HD or CAPD. The measurements were repeated in a group of
      patients who received a successful renal transplant to see whether the
      coagulopathy associated with CRF would be corrected by this lasting therapy. The
      study, which was mainly cross-sectional and prospective, included two groups: 49
      patients with CRF with their age ranging from 17 to 67 years were divided as
      follows: those on regular HD (n=20), CAPD (n=9) and patients after transplant
      (n=20). The tests were also done on 34 healthy controls. Significant hyper
      fibrinogenemia was recorded in all three study groups. The HD group showed
      significant elevation in the plasma levels of AT III and total protein S and a
      significant reduction in free protein S and protein C, when compared with healthy
      controls. These inhibitors, except total PS, displayed similar fluctuations in
      the CAPD group. In the transplant patients, there was significant elevation of AT
      III and total protein S, a reduction in free PS and no significant changes in PC
      levels. A significant elevation was found in the levels of F1+2, TAT and D-Dimer
      in HD and in transplant patients, when compared with controls. In CAPD patients,
      only D-Dimer levels showed a significant increase. The tPA and PAI-1 levels in
      the three study groups were similar to the control group. Our study revealed
      significant activation of the hemostatic system, more pronounced in patients on
      HD than CAPD. This coagulopathy remained only partly corrected following
      successful kidney transplantation.

PMID- 17496392
TI  - The effect of rectourogenital fistula in high imperforate anus.
AB  - To determine the incidence of rectourogenital fistulae and the possible role of
      fistulae on the mechanism of defecation in patients with high imperforate anus,
      we retrospectively studied 42 children, 38 males and four females, all with high
      imperforate anus presenting in the period from 1982 to 1995. All children
      underwent radiological evaluation, to determine the level of the rectal pouch 18
      24 hours after birth and to study the bony spine. A preliminary colostomy was
      performed in all patients after the diagnosis shortly after birth.
      Ultrasonography was performed in all the cases to assess the kidneys and ureters.
      All patients but one was operated on via a posterior sagittal anorectoplasty.
      Bowel control was assessed clinically regarding the presence of voluntary bowel
      movement, fecal soiling, incontinence and constipation. Eighteen (42.8%) patients
      were found to have recto-urogenital fistulae; 15 rectourethral, two rectovaginal
      and one rectovesical. Outcomes were known for 36 out of 42 patients; 15(41.6 %)
      had voluntary bowel movements, nine (25 %) had soiling, six (16.6%) had
      constipation and six (16.6 %) had incontinence. In conclusion, the presence of
      rectourogenital fistula in patients with high imperforate anus is another new
      prognostic factor for anorectal function which needs further clarification.

PMID- 17496393
TI  - Epidemiology of chronic renal failure in Iran: a four year single- center
      experience.
AB  - Chronic renal failure (CRF) is a major public health problem. Early diagnosis and
      proper management have important roles in prevention of CRF progression to end
      stage renal disease (ESRD). For this purpose, determining the etiology of CRF may
      be helpful. This study was conducted in the nephrology department at the Mostafa
      Khomeini Hospital in Tehran, Iran from March 2001 to March 2005, to determine the
      etiology of CRF in adult Iranian patients. A total of 1200 patients with a
      diagnosis of CRF were involved in the study. Relevant data were collected using a
      reliable questionnaire. All data analyses were carried out using SPSS and the
      chi2 test. Of the 1200 patients, 61% were males and 39% females. The most
      frequent age group was 61-75 years (38.3%) and the mean age of the study patients
      was 51.6 +/- 17 years. The etiology of CRF in our series included: diabetes
      mellitus in 26.8%, hypertension in 13.5%, obstructive uropathy in 12%, cystic and
      congenital disorders in 10.3%, glomerulonephritis in 6.5%, urinary tract
      infections in 4%, vasculitis in 2%, tubulo-interstitial nephritis and pregnancy
      related in 0.8% each and unknown causes in 29.5% of the patients. Laboratory and
      ultrasonographic assessment at initiation of the study revealed blood urea
      nitrogen> 100 mg/dl in 57.8% of the patients, serum creatinine> 10 mg/dl in
      40.3%, glomerular filtration rate (GFR) < 10 ml/min in 61.3%, hemoglobin < 10
      g/dl in 65.8% and kidney size lesser than 8 cm in 46% of the cases. There was a
      significant statistical relationship between kidney size and duration of
      hypertension greater than five years (P = 0.017). The high frequency of CRF of
      unknown etiology in this study may be attributed to diagnostic limitations
      prevailing in our country. A GFR of < 10 ml/min in 61.3% of the cases at
      presentation suggests late diagnosis and/or referral. Aggressive screening and
      treatment strategies to prevent ESRD are recommended.

PMID- 17496394
TI  - Peritoneal dialysis for adults with acute renal failure: an underutilized
      modality.
AB  - In order to evaluate the effects of peritoneal dialysis as a modality of renal
      replacement therapy for adults with acute renal failure (ARF) of varied
      etiologies, we studied 43 ARF patients who underwent peritoneal dialysis at our
      hospital from April 2004 to November 2005. The age of the patients ranged from 18
      to 75 years with a mean of 35 years. There was no significant difference in the
      incidence of ARF between males and females. Acute tubular necrosis secondary to
      acute gastroenteritis was the cause of ARF in 32 (80%) patients; four (10%)
      patients expired secondary to ARF. There was an average fall of around 60% in the
      S. creatinine at the end of PD. We did not notice any significant complications
      related to the procedure. We conclude that peritoneal dialysis is still a good
      option for the treatment of patients with ATN.

PMID- 17496395
TI  - Comparison of the effect of body position, prone or supine, on the result of
      extracorpreal shock wave lithotripsy in patients with stones in the proximal
      ureter.
AB  - The aim of this study was to determine whether positioning of the patient, prone
      or supine, plays a significant role on the treatment of stones in the proximal
      ureter with extracorporeal shock wave lithotripsy (ESWL). 68 patients with
      proximal ureteric stones underwent ESWL. The procedure was performed in the
      supine position in 35 (Group 1) and the prone position in 33 patients (Group 2).
      Stone-free rates, repeat ESWL rates, shocks per patient and shocks per session
      were compared in both groups. The mean session number per patient was 1.93 +/-
      0.82 in Group 1 and 1.88 +/- 0.79 in Group 2 (P = 0.786). The stone-free rates,
      three months after ESWL, were 81.8% in Group 1 and 82.9% in Group 2 (P = or >
      0.05). Thus, these two parameters were similar in both Groups. Also, the number
      of shocks per session was 3066.1 +/- 346.3 in Group 1 and 3148.5 +/- 621.0 in
      Group 2. This difference was nonsignificant (P = 0.49). Our study suggests that
      the treatment of proximal ureteric stones with ESWL in the prone position is as
      safe and effective as when the patient is placed in the supine position.

PMID- 17496396
TI  - The Gulf Survey on Anemia Management (GSAM 2005).
AB  - We conducted this study to determine the achievements of the current practice
      guidelines in the management of anemia in the Arabian Gulf Countries. The survey
      was designed as a retrospective, one day screening of adult patients with end
      stage renal disease in six Arabian Gulf countries including Saudi Arabia, Kuwait,
      Bahrain, Oman, United Arab Emirates and Qatar. Data were collected on patients
      undergoing chronic dialysis. For random patient sampling, each participating
      center drew up an alphabetical list of all hemodialysis (HD) or peritoneal
      dialysis (PD) patients which were 18 years or older and selected every fourth
      patient on the list. A total of 563 patients from 18 centers were included in the
      survey. The most common cause of end-stage renal failure was diabetic
      nephropathy, closely followed by chronic glomerulonephritis. The majority of
      patients were treated by HD, with only 20% receiving PD. The mean (+/-SD)
      hemoglobin (Hgb) concentration was 115 +/- 15 g/L (median, 115 g/L; range, 61-159
      g/L). The Hgb concentration was > or = 110 g/L in 28%, > or = 120 g/L in 38% and
      < 100 g/L in 16%. Information on their iron status was available for 97% of
      patients, ferritin levels were available for 97% and TSAT values for 67% were
      available. The mean serum ferritin concentration for the study patients was 503
      +/- 406 ng/ml (median, 390 ng/ml; range, 20.0-2960 ng/ml); 90.5% had a serum
      ferritin concentration > 100 ng/ml. We conclude that the results of our study
      demonstrate anemia management in the Gulf countries which is comparable to the
      European Survey on Anemia Management 2003 (ESAM 2003). However, many patients
      still have not reached the current recommendation of anemia management.

PMID- 17496397
TI  - The influence of serum 25-hydroxy vitamin D levels on Helicobacter Pylori
      Infections in patients with end-stage renal failure on regular hemodialysis.
AB  - This study was designed to determine whether the serum levels of 25-OH vitamin D
      influence the occurrence of infection with Helicobacter Pylori (H.Pylori) in
      patients on maintenance hemodialysis (HD). The study subjects were patients with
      end-stage renal disease who were undergoing maintenance dialysis at the
      hemodialysis section, Hajar Medical, Educational and Therapeutic Center,
      Shahrekord, Iran. The serum 25-OH vitamin D level and serum H. Pylori specific
      IgG antibody titers were measured using an enzyme-linked immunosorbent assay
      (ELISA) method. A total of 36 patients were studied including 21 males and 15
      females. The mean age of the study group was 47 (+/- 17) years. The mean level of
      serum 25-OH vitamin D was 0.5 +/- 18.7 nmol/L (median: 3.5) while the mean value
      of serum H.Pylori specific IgG antibody titer was 7.7 (+/-9.9) u/ml (median: 2
      u/ml). Thus, a significant positive correlation was found between the levels of
      serum 25-OH vitamin D and serum H. Pylori specific IgG antibody titers (data
      adjusted for age, urea reduction rate, duration and dose of dialysis) (r=0.36,
      p=0.043). Our study suggests that vitamin D may positively affect the chronic
      inflammatory status of dialysis patients and may potentiate the immune response
      in such patients. Because of this immuno-modulatory effect, vitamin D analogs may
      offer new means to control the inflammatory status in patients on maintenance
      dialysis.

PMID- 17496398
TI  - Patterns of "severe acute renal failure" in a referral center in Sudan: excluding
      intensive care and major surgery patients.
AB  - Acute renal failure (ARF) is a common health problem worldwide. There is limited
      data on the pattern of ARF in Sudan. Moreover, glomerular diseases, which are a
      well-known cause of ARF, have not been accurately and adequately diagnosed
      previously. A retrospective study on the patterns of ARF was carried out in a
      general nephrology referral center in Sudan during the period from February 2003
      February 2004. Patients from intensive care units with ARF and those who
      developed ARF after massive surgery were excluded from the study. Renal biopsy
      was performed when indicated and studied with light and immunofluorescent
      microscopy. Eighty-nine patients (57 (64%) cases were males and mean age was 39+/
      19.4 years) fulfilled the criteria for the diagnosis of advanced renal failure
      requiring renal function replacement therapy. Acute tubular necrosis (ATN) was
      diagnosed in 50 (56%) patients; 33 (66%) ATN patients had renal failure as a
      complication of volume depletion, fulminant infections (particularly malaria and
      typhoid fever) or snakebites and 12 (13.4%) patients ingested paraphenylene
      diamine (PPD) (hair/Henna dye) in suicidal attempts. Eight (9%) patients of the
      total study group had glomerular diseases and 11 (12.3%) had obstructive uropathy
      associated with ARF; the cause of ARF could not be determined in 17 (19%)
      patients. Fifty-three (60%) patients recovered their renal function, six (6.7%)
      patients progressed to chronic kidney disease (CKD), 16 (18%) died and 14 (16%)
      were lost to follow-up. In conclusion, patients with ARF associated with ATN had
      a favorable prognosis except when ATN was associated with PPD poisoning.

PMID- 17496399
TI  - Pathogenesis of focal and segmental glomerulosclerosis: a review.

PMID- 17496400
TI  - Successful treatment of chyluria, glomerular and tubular abnormalities in a young
      lady with silver nitrate instillation.
AB  - A 21- year-old lady presented with chyluria, severe malnutrition, secondary
      amenorrhea, profound hypoalbuminemia, heavy proteinuria and renal tubular
      abnormalities suggestive of Type IV renal tubular acidosis. No particular cause
      for chyluria could be ascertained. She was successfully treated with an injection
      of 2% silver nitrate into the left ureter and urinary bladder. She continues to
      be well after 15 years of follow-up.

PMID- 17496401
TI  - Goodpasture's syndrome - four case reports.
AB  - Goodpasture's syndrome (GPS) is a rare but severe immunological disease, which is
      characterised by rapidly progressive glomerulonephritis and intraalveolar
      hemorrhage (IAH) with the presence of anti-glomerular basement membrane (GBM)
      antibodies. We report four cases of GP's syndrome referred to the nephrology unit
      at Ibn Rochd UHC in Casablanca from January 1995 to December 2003. All patients
      had rapidly progressive glomerulonephritis (RPGN) with proteinuria and
      microscopic hematuria. Elevated blood pressure was noted in one case. IAH was
      manifested as hemoptysis in two cases, radiological signs in three cases and
      confirmed by broncho-alveolar lavage in all cases. Laboratory assessment revealed
      anemia in all cases. Renal biopsy showed extracapillary glomerulonephritis with
      linear deposits of IgG along the GBM. Renal failure was severe and hemodialysis
      was required in all cases. All patients were treated with prednisone and
      cyclophosphamide and none recovered renal function. Two patients died due to
      severe lung hemorrhage.

PMID- 17496402
TI  - Successful prevention of tunneled, central catheter infection by antibiotic lock
      therapy using vancomycin and gentamycin.
AB  - Tunneled, cuffed central vein catheters (TCC) are widely used for delivering
      hemodialysis (HD). Among the complications associated with central vein catheters
      in HD patients, infection is the principal cause of morbidity and mortality. The
      optimal strategy for management of TCC infections is unclear. This prospective
      study was aimed at assessing the efficacy of antibiotic-lock therapy using
      vancomycin and gentamycin in preventing catheter-related blood stream bacterial
      infection in patients on HD. A total of 63 HD patients with 81 TCC were enrolled
      at the time of catheter insertion. Patients were randomized into two groups:
      Group I (33 patients, 37 insertions) included TCC with antibiotic lock therapy
      and Group II (30 patients, 44 insertions) with routine TCC management. Infection
      free catheter survival of both groups was evaluated and compared at the end of
      the 12-month study period. A total of 57 TCC infections were encountered with an
      incidence rate of 8.95 infections per 1000 dialysis sessions (DS). The rate of
      infection was significantly lower in Group I (4.54 per 1000 DS) as compared to
      Group II (13.11 per 1000 DS), p 0.05). Our study suggests that antibiotic-lock
      therapy using a combination of vancomycin and gentamycin is useful in preventing
      catheter-related blood stream infection in patients on HD.

PMID- 17496403
TI  - Unusual causes of sudden anuria in renal transplant patients.
AB  - Sudden unexplained anuria in renal transplant patients could well be secondary to
      occult internal hemorrhage rather than the usual vascular thrombotic or
      obstructive event, even in the completely stable patient. Urgent intervention in
      such bleeding states can save a patient's life and graft function. Graft survival
      is very exceptional in graft artery or vein thrombosis. Contrary to hemorrahagic
      events, life is usually not threatened by thrombotic events involving the renal
      graft vasculature. We present here three unfortunate cases that shared the
      problem of unexpected anuria due to a hemorrhagic event in apparently stable
      renal transplant patients.

PMID- 17496404
TI  - Oxalosis presenting as early renal allograft failure.
AB  - Hyperoxaluria can result in the deposition of oxalate in bones, arteries, eyes,
      heart, nerves, kidneys and other structures when there is a reduction in
      glomerular filtration rate. Liver and kidney transplantation is curative for
      patients with Type I primary hyperoxaluria. Here we report a case of recurrent
      oxalosis in a post-transplant kidney with early graft failure in an adult male.

PMID- 17496405
TI  - Successful pregnancy in a patient with hemodialysis in Iraq.
AB  - An 18-year-old woman patient was discovered to have severe anemia and advanced
      renal failure during a routine prenatal follow-up at her 6th week of gestation.
      During the first few weeks of therapy, the hemodialysis frequency was increased
      gradually and Erythropoietin was administered with intravenous iron therapy to
      keep the patient's hemoglobin above 115 gm/L. Blood pressure rose was controlled
      by alpha methyldopa. Obstetric follow-up consisted of monitoring the fetal
      activity and growth, placental maturity and umbilical artery perfusion. On the
      32nd week of gestation, the patient had a normal vaginal delivery of live female
      weighing 2,100 gm. the patient had a completely uneventful postpartum course and
      the newborn baby was well. In conclusion, our index case illustrates that
      intensified dialysis regimens and attentive medical care results in a successful
      outcome of pregnancy in patients with end stage renal disease on hemodialysis.

PMID- 17496406
TI  - Possible increased risk of pulmonary edema in patients with hepatorenal syndrome
      on adding octreotide to albumin / noradrenaline therapies.

PMID- 17496407
TI  - Up-date on renal fibrosis: a time for action.

PMID- 17496408
TI  - Anaesthesia and I.

PMID- 17496409
TI  - Adult-to-adult living related donor renal transplantation in Yemen: the first
      experience.
AB  - Between May 1998 and June 2006, 31 patients (21 males and 10 females) received a
      renal allograft from live-related donors at the Urology and Nephrology Center in
      the Al-Thawra Modern General Hospital Sana'a, Republic of Yemen. The cold
      ischemia time ranged between 48 and 68 minutes. The immunosuppressive protocol
      was double therapy (steroids and mycophenolate) in the first 8 cases. The
      subsequent cases received triple therapy with steroids, cyclosporine and
      mycophenolate. Episodes of acute rejection were treated with high dose steroids
      while anti-thymocyte globulin (ATG) was also used in cases of vascular or steroid
      resistant rejection. Primary graft function was achieved in 29 recipients
      (93.5%). The post-transplant complications, either surgical or medical, were
      comparable to those reported in the literature. The kidney transplantation
      program started sporadically in Yemen since 1998. However, a well-established
      program has been running regularly since the beginning of 2005.

PMID- 17496410
TI  - Organ failure in Syria: initiating a national deceased donation program.
AB  - In the absence of formal registry data, the volume and causes of organ failure in
      Syria are difficult to establish with certainty. However, we evaluated in this
      study the extent of organ failure by collecting data from health care authorities
      in different medical institutions who are involved in caring for patients with
      organ failure. Subsequently, we assessed the problem of the widening gap between
      organ supply and demand in our country and we highlighted the obstacles to
      initiating a national deceased donation program as a viable option to address the
      challenge of organ shortage. The estimated prevalence of corneal blindness in
      Syria is 2.3 per one thousand population. The estimated incidence of viral
      induced cirrhosis is 49 - 67 per one million population (pmp); these include both
      HCV and HBV, which constitute the leading causes of liver failure. We estimated
      the incidence of end-stage renal disease (ESRD) to be from 80 - 100 pmp.
      Obstacles to initiating a national deceased donation program include lack of
      awareness of the public at large and health care professionals to the importance
      of organ donation and transplantation. Other obstacles include lack of adequate
      resources in terms of finance, personnel and services and the unavailability of a
      national center for organ transplantation that influences public attitude, sets
      national guidelines and supervises all activities related to organ donation and
      transplantation.

PMID- 17496411
TI  - Ultrasound assessment of renal size in healthy term neonates: a report from Benin
      City, Nigeria.
AB  - Knowledge of the normal range of renal size is useful in appreciating variations
      that may occur due to morbidities. Ultrasound is a simple and safe method of
      evaluating renal sizes in all age groups. This is a prospective study of the
      assessment of renal dimensions in apparently healthy neonates at the University
      of Benin Teaching Hospital, Nigeria. One hundred and fifty neonates were studied,
      including eighty-five males (56.7%) and sixty-five females (43.3%). The mean
      length of the right kidney was 44.9 +/- 3.2 mm and the mean length of the left
      kidney was 44.4 +/- 3.5 mm. The difference in renal length between the two sides
      was not statistically significant. The height and weight of the child showed
      strong correlation with longitudinal renal measurements. The study also showed
      the independence of neonatal renal sizes on gender and race.

PMID- 17496412
TI  - Bronchoalveolar lavage in interstitial lung diseases: does the recovery rate
      affect the results?
AB  - BACKGROUND: Bronchoalveolar lavage (BAL) is an established diagnostic tool in
      interstitial lung diseases. BAL frequently yields findings of diagnostic value
      and at times even confirmatory diagnostic results. OBJECTIVES: The present study
      has been designed to investigate whether the recovery rate affects BAL results
      relative to the instilled volume. METHODS: Six hundred and eighteen patients with
      the following diagnoses were included into the study: 236 with sarcoidosis, 85
      with idiopathic pulmonary fibrosis, 83 with cryptogenic organizing pneumonitis,
      64 with connective tissue disease affecting the lungs, 54 with respiratory
      bronchiolitis with interstitial lung disease, 51 with extrinsic allergic
      alveolitis and 45 control patients. BAL was performed during flexible
      bronchoscopy with an irrigation volume of 100 ml 0.9% saline solution in 5
      aliquots of 20 ml each. Only patients with a recovery of at least 30 ml were
      evaluated. Initially, the entire patient population was analysed, followed by an
      analysis within the different diagnostic groups and a comparison between patients
      with a high (>50 ml) and low (< or =50 ml) recovery rate. RESULTS: The recovery
      rate varied between the diagnostic groups (p < 0.001) and was negatively
      correlated with age (r = -0.21, p < 0.001) and smoking history (r = -0.11, p <
      0.035). There were no correlations with inspiratory vital capacity (%pred.; p =
      0.26) and forced expiratory volume in 1 s (%pred.; p = 0.15), but a positive
      correlation with the index (forced expiratory volume in 1 s/inspiratory vital
      capacity) x 100 (r = 0.23, p < 0.001). The cellular and non-cellular constituents
      of BAL were not affected by the recovery: cells/millilitre BAL (p = 0.71),
      relative proportion of macrophages (p = 0.92), lymphocytes (0 = 0.33),
      neutrophils (p = 0.14) and eosinophils (p = 0.11), albumin concentration (p =
      0.13), and proportion of albumin in total protein (p = 0.06). The same applied
      for the lymphocyte surface markers CD4 (p = 0.72) and CD8 (p = 0.53). In the
      group with a high recovery rate, patients with sarcoidosis had a lower proportion
      of eosinophils (p = 0.04) and patients with cryptogenic organizing pneumonitis a
      higher concentration of albumin (p = 0.02) and lymphocytes (p = 0.007).
      Otherwise, no further differences were detected. CONCLUSIONS: The recovery rate
      hardly affected the cellular and non-cellular constituents of BAL at a lower
      limit of 30% of the instilled volume.

PMID- 17496413
TI  - Cytotoxic activity of schisandrolic and isoschisandrolic acids involves induction
      of apoptosis.
AB  - Cycloartane triterpenoid schisandrolic acid and isoschisandrolic acid were
      isolated from Schisandra propinqua (Wall.) Baill (Schisandraceae). Their
      cytotoxicity was evaluated in several cancer cell lines and primary cultured
      normal mouse hepatocytes. The two triterpenoids showed moderate cytotoxic
      activity on all tested cell lines. Fluorescence staining and cell cycle analyses
      were employed to elucidate the primary mechanisms of their cytotoxicity. Our
      results showed that two triterpenoids exerted their cytotoxic activity via
      G(0)/G(1) arrest and subsequent apoptosis. Furthermore, proteolytic cleavage of
      poly-ADP-ribose polymerase (PARP), substrate of the caspase family, was detected
      and associated with apoptosis in HepG2 cells induced by the two compounds.

PMID- 17496414
TI  - Sequential administration of 5-fluorouracil (5FU)/leucovorin (LV) followed by
      irinotecan (CPT-11) at relapse versus CPT-11 followed by 5-FU/LV in advanced
      colorectal carcinoma. A phase III randomized study.
AB  - PURPOSE: The purpose of the present study was to evaluate the differences in the
      sequence of administration of 5-fluorouracil (5-FU)/leucovorin (LV) followed by
      irinotecan (CPT-11), or CPT-11 followed by 5-FU/LV in advanced colorectal cancer
      (ACC). PATIENTS AND METHODS: Chemotherapy-naive patients with ACC were allocated
      to the following treatment groups: group A, a bolus of 20 mg/m(2) LV and 425
      mg/m(2) 5-FU for 5 days until progression/relapse, and upon progression treatment
      with weekly CPT-11 (100 mg/m(2)), and group B, CPT-11 followed at
      progression/relapse by 5-FU/LV at the same doses and schedules as in group A.
      RESULTS: 120 patients were randomized to receive one of the two treatment
      sequences and their pretreatment characteristics were equally balanced between
      treatment arms. No statistically significant difference was found in the
      objective response rate to CPT-11 (p = 0.45); partial response (PR) was 23.3% for
      group A patients and 33.3% for group B. Following documented progression and
      second line treatment there was a significant difference between the response
      rate in group A (23.3%) and group B where no patients were found to respond to
      second-line treatment with 5-FU/LV (p = 0.024). The median overall survival was
      42.0 weeks (range, 36.6-47.4 weeks) for group A and 32.0 weeks (range, 28.2-35.8
      weeks) for group B. The median time to progression for patients in group A
      following first-line 5-FU/LV was 18 weeks (range, 10-36 weeks) and 12 weeks
      (range, 10-16 weeks) for group B following first-line CPT-11 (p = 0.0005).
      Toxicity, according to WHO, was similar between groups. CONCLUSIONS: Treating
      patients with CPT-11 upon progression to 5-FU/LV treatment seems to be superior
      to the opposite sequence. We used these treatments as sequential monotherapies
      (at progression/relapse), and the best results are gained when 5-FU/LV is
      followed by CPT-11 at disease progression or relapse.

PMID- 17496415
TI  - Sustained virological response in the antiviral therapy of chronic hepatitis C:
      is there a predictive value of interferon-induced depression?
AB  - BACKGROUND: The study objective was to determine the contribution of cytokine
      induced depression to a predictive model of sustained virological response (SVR)
      in chronic hepatitis C. METHODS: One hundred and one therapy-naive hepatitis C
      virus (HCV) outpatients received treatment with peginterferon alfa-2b and
      ribavirin. Neuropsychiatric side effects were monitored prospectively (Hospital
      Anxiety and Depression Scale, DSM-IV criteria for major depression). SVR was
      defined as a failure to detect HCV by PCR 24 weeks after therapy. RESULTS: SVR
      rate was 72.3% (73 of 101 patients). Classification data and the extent of
      interferon-induced depression were not significantly linked to SVR. Virus
      genotype (p = 0.045) and gender (p = 0.016) contributed significantly to a
      logistic regression model. Mean (p = 0.811) and maximum (p = 0.744) depression
      increases were no significant predictors of SVR. Major depression rates (DSM-IV
      criteria) were 12.3% (9 of 73 patients) in the subgroup with SVR and 10.7% (3 of
      28) in patients without SVR. CONCLUSIONS: We found no significant association
      between depression and the efficacy of antiviral treatment in chronic hepatitis
      C. Interferon-induced depressive symptoms are important to be monitored and
      treated if necessary; however, they cannot be used to predict therapy success.

PMID- 17496416
TI  - Antifungal susceptibility of Cryptococcus neoformans isolates in HIV-infected
      patients to fluconazole, itraconazole and voriconazole in Spain: 1994-1996 and
      1997-2005.
AB  - The antifungal drug susceptibility of 70 Cryptococcus neoformans isolates
      obtained in Spain from 1994 to 1996 (23 isolates) and from 1997 to 2005 (47
      isolates) was investigated. The MICs of fluconazole, itraconazole and
      voriconazole were determined by the modified Clinical and Laboratory Standards
      Institute (CLSI; formerly National Committee for Clinical Laboratory Standards)
      broth microdilution method. The MIC(50) and MIC(90) for itraconazole and
      voriconazole did not change significantly from 1994 to 2005. The MIC(50) of
      fluconazole remained stable and the MIC(90) decreased by 2 log(2) dilution in the
      isolates collected from 1997 to 2005. We conclude that the in vitro resistance to
      fluconazole decreased over an 11-year period. In addition, a tendency for the
      development of possible cross-resistance between the three triazoles was
      observed.

PMID- 17496417
TI  - Memantine in moderate to severe Alzheimer's disease: a meta-analysis of
      randomised clinical trials.
AB  - The efficacy of memantine in Alzheimer's disease (AD) has been investigated in
      multiple randomised, placebo-controlled phase III trials. Recently, the
      indication label for memantine in Europe was extended to cover patients with
      moderate to severe AD, i.e. Mini-Mental State Exam total scores below 20. The
      efficacy data for memantine in this patient subgroup has been summarised by a
      meta-analysis of 1,826 patients in six trials. Efficacy was assessed using
      measures of global status (Clinician's Interview-Based Impression of Change Plus
      Caregiver Input), cognition (Alzheimer's Disease Assessment Scale - Cognitive
      Subscale, or Severe Impairment Battery), function (Alzheimer's Disease
      Cooperative Study Activities of Daily Living 19- or 23-item scale), and behaviour
      (Neuropsychiatric Inventory). Results (without replacement of missing values)
      showed statistically significant effects for memantine (vs. placebo) in each
      domain. Memantine was well tolerated, and the overall incidence rates of adverse
      events were comparable to placebo. This meta-analysis supports memantine's
      clinically relevant efficacy in patients with moderate to severe AD.

PMID- 17496418
TI  - Comparison of two antacid preparations on intragastric acidity--a two-centre open
      randomised cross-over placebo-controlled trial.
AB  - BACKGROUND: Rennie and Riopan Gel are 2 of the most well-known and popular over
      the-counter antacids; for heartburn symptoms, pain relief is fast with both
      preparations. A direct comparison with respect to intragastric acidity has not
      been done yet. The aim of our study was therefore to compare the effects of both
      preparations on intragastric acidity of fasting volunteers. METHODS: The study
      was conducted as an open, randomised, placebo-controlled, 2-centre cross-over
      study. On different days, 24 healthy adult volunteers (11 males and 13 females)
      received equimolar acid-neutralising amounts of either Riopan Gel (800 mg
      magaldrate) or 2 tablets of Rennie (680 mg calcium carbonate and 80 mg magnesium
      carbonate) or no drug (control) with a wash-out period of at least 4 days between
      applications. The intragastric pH was measured for 3 h by intragastric pH-metry.
      The primary endpoint was the median time lag before intragastric pH >3.0 was
      reached for 10 consecutive min after drug administration. RESULTS: For both
      antacids, the median pH during the first 30 min after drug administration was
      statistically significantly different from placebo (p < 0.05), but there was a
      statistically significant increase in pH during the first 5 min for Riopan Gel
      only. CONCLUSION: Compared to placebo, both antacids (Rennie and Riopan Gel) have
      short-lasting effects on intragastric acidity. There is no statistically
      significant difference between the 2 preparations, except in the first 5 min,
      indicating a faster onset of action for Riopan Gel. We conclude that the antacid
      formulation (tablet or liquid) has little influence on intragastric acidity.

PMID- 17496419
TI  - Use of the hemostatic agent QuikClot for the treatment of massive splenic injury
      in a rat model.
AB  - BACKGROUND: In the present study, QuikClot (QC) was used to treat intra-abdominal
      bleeding induced by massive splenic injury (MSI) in rats. STUDY DESIGN: 40
      animals were divided into five groups: (1) sham operated; (2) MSI untreated; (3)
      MSI treated with 41.5 ml/kg lactated Ringer's solution (RL); (4) MSI treated with
      QC, and (5) MSI treated with QC and RL. RESULTS: Untreated MSI was followed by
      mortality of 60%, total blood loss (TBL) of 33.69% and mean survival time (MST)
      of 153.9 min. MSI treatment with RL resulted in mortality of 100%, TBL of 61.8%
      (p < 0.001), and MST of 92.2 min (p < 0.05). MSI treated with QC was followed by
      TBL of 14.1% (p < 0.005) and MST of 237.5 min (p < 0.05) with no mortality. MSI
      treated by QC and RL led TBL of 27.4% (p < 0.001 vs. group 3), and MST of 233.3
      min (p < 0.05) and no mortality. CONCLUSIONS: QC significantly reduced blood loss
      from the injured spleen with improved survival. Combination of RL and QC
      prevented the increase in blood loss and improved survival compared to RL alone.

PMID- 17496420
TI  - Vocal responses of captive gibbon groups to a mate change in a pair of white
      cheeked gibbons (Nomascus leucogenys).
AB  - The singing behaviour of 3 pairs of white-cheeked gibbons (Nomascus leucogenys)
      held at the Perth Zoo was observed for 6 months in 2005. These groups included a
      family (mated pair and 2 immature offspring) and a pair without offspring. During
      the study, the female without offspring was exchanged for an unpaired female from
      New Zealand. After the new pair had been released onto the island enclosure and
      began to duet, the duetting rate of the white-cheeked gibbon family increased.
      The increased singing began after the new female had started to sing solo female
      great calls. These observations support the hypothesis that duets have an
      intergroup communication function in white-cheeked gibbons. The pair that duetted
      most frequently also copulated most frequently but allogroomed the least. We
      suggest that duetting may be more important to intergroup relations than to pair
      bond maintenance in this species.

PMID- 17496421
TI  - A case of 3beta-hydroxysteroid dehydrogenase type II (HSD3B2) deficiency picked
      up by neonatal screening for 21-hydroxylase deficiency: difficulties and delay in
      etiologic diagnosis.
AB  - BACKGROUND: 3beta-Hydroxysteroid dehydrogenase type II deficiency, a rare form of
      congenital adrenal hyperplasia, is characterized by varying degrees of salt loss
      and incomplete masculinization in males and mild virilization or normal external
      genitalia in females. The clinical signs may be difficult to recognize,
      increasing the risk of a neonatal adrenal crisis. In addition, elevated 17alpha
      hydroxyprogesterone and androstenedione levels due to peripheral HSD3B1 activity
      may lead to a delay of the correct diagnosis and even to misdiagnosis as CYP21
      deficiency. METHOD: We report a patient who was detected on neonatal screening
      for 21-hydroxylase deficiency, in part because of cross-reactivity in the
      commonly used assay. RESULTS: The diagnostic difficulties in this case were
      overcome by the use of more specific antibodies. CONCLUSION: This case emphasizes
      the importance of confirming the etiological diagnosis with molecular genetic
      analyses.

PMID- 17496423
TI  - Molecular characterization of arginine kinase, an allergen from the shrimp
      Litopenaeus vannamei.
AB  - BACKGROUND: Consumption of seafood can produce allergic symptoms in susceptible
      individuals and crustacean allergies are the most frequently reported causes of
      allergic reactions. METHODS: An allergen from the muscle of the white shrimp
      Litopenaeus vannamei was purified by ion exchange chromatography and identified
      by mass spectrometry of tryptic peptides and its specific enzymatic activity.
      Moreover, the corresponding full-length cDNA was obtained from an L. vannamei
      muscle cDNA library. RESULTS: A 40-kDa protein was purified and identified as
      arginine kinase and its cDNA of 1.4 kb encoded a 356 amino acid protein. The
      obtained arginine kinase was recognized by IgE in serum from shrimp-allergic
      individuals using ELISA and immunoblotting analysis. CONCLUSIONS: This is the
      first allergen reported for the Pacific white shrimp species; it was named Lit v
      2 and has a 96% identity to Pen m 2 from Penaeus monodon.

PMID- 17496422
TI  - Wheat IgE-mediated food allergy in European patients: alpha-amylase inhibitors,
      lipid transfer proteins and low-molecular-weight glutenins. Allergenic molecules
      recognized by double-blind, placebo-controlled food challenge.
AB  - BACKGROUND: Three main problems hamper the identification of wheat food
      allergens: (1) lack of a standardized procedure for extracting all of the wheat
      protein fractions; (2) absence of double-blind, placebo-controlled food challenge
      studies that compare the allergenic profile of Osborne's three protein fractions
      in subjects with real wheat allergy, and (3) lack of data on the differences in
      IgE-binding capacity between raw and cooked wheat. METHODS: Sera of 16 wheat
      challenge-positive patients and 6 patients with wheat anaphylaxis, recruited from
      Italy, Denmark and Switzerland, were used for sodium dodecyl sulfate
      polyacrylamide gel electrophoresis/immunoblotting of the three Osborne's protein
      fractions (albumin/globulin, gliadins and glutenins) of raw and cooked wheat.
      Thermal sensitivity of wheat lipid transfer protein (LTP) was investigated by
      spectroscopic approaches. IgE cross-reactivity between wheat and grass pollen was
      studied by blot inhibition. RESULTS: The most important wheat allergens were the
      alpha-amylase/trypsin inhibitor subunits, which were present in all three protein
      fractions of raw and cooked wheat. Other important allergens were a 9-kDa LTP in
      the albumin/globulin fraction and several low-molecular-weight (LMW) glutenin
      subunits in the gluten fraction. All these allergens showed heat resistance and
      lack of cross-reactivity to grass pollen allergens. LTP was a major allergen only
      in Italian patients. CONCLUSIONS: The alpha-amylase inhibitor was confirmed to be
      the most important wheat allergen in food allergy and to play a role in wheat
      dependent exercise-induced anaphylaxis, too. Other important allergens were LTP
      and the LMW glutenin subunits.

PMID- 17496424
TI  - A proteomic study to identify soya allergens--the human response to transgenic
      versus non-transgenic soya samples.
AB  - BACKGROUND: In spite of being among the main foods responsible for allergic
      reactions worldwide, soybean (Glycine max)-derived products continue to be
      increasingly widespread in a variety of food products due to their well
      documented health benefits. Soybean also continues to be one of the elected
      target crops for genetic modification. The aim of this study was to characterize
      the soya proteome and, specifically, IgE-reactive proteins as well as to compare
      the IgE response in soya-allergic individuals to genetically modified Roundup
      Ready soya versus its non-transgenic control. METHODS: We performed two
      dimensional gel electrophoresis of protein extracts from a 5% genetically
      modified Roundup Ready flour sample and its non-transgenic control followed by
      Western blotting with plasma from 5 soya-sensitive individuals. We used peptide
      tandem mass spectrometry to identify soya proteins (55 protein matches),
      specifically IgE-binding ones, and to evaluate differences between transgenic and
      non-transgenic samples. RESULTS: We identified 2 new potential soybean allergens-
      one is maturation associated and seems to be part of the late embryogenesis
      abundant proteins group and the other is a cysteine proteinase inhibitor. None of
      the individuals tested reacted differentially to the transgenic versus non
      transgenic samples under study. CONCLUSION: Soybean endogenous allergen
      expression does not seem to be altered after genetic modification. Proteomics
      should be considered a powerful tool for functional characterization of plants
      and for food safety assessment.

PMID- 17496425
TI  - Anaphylaxis from mandarin (Citrus reticulata): identification of potential
      responsible allergens.
AB  - We report on a patient with anaphylaxis from mandarin. Temporal relationship
      between consumption of the fruit, the presence of positive specific IgE, the
      positive skin test and the basophil activation test for mandarin strongly
      supported the diagnosis of an IgE-mediated allergy from mandarin. The lipid
      transfer protein allergen from mandarin fruit was isolated and characterized.
      Specific IgE levels and IgE immunodetection data indicated the patient's
      sensitization to orange (Cit s 3) and mandarin (Cit r 3) lipid transfer protein
      allergens, as well as to germin-like (Cit s 1) allergen. These results were fully
      confirmed by skin prick test and basophil activation test (BAT) for lipid
      transfer proteins, and a BAT for Cit s 1. This case report has several
      particularities. First, in Central and Northern Europe, it is not widely
      appreciated that citrus fruits, particularly mandarin, can elicit anaphylaxis.
      Second, this case report re-emphasizes sensitization from lipid transfer proteins
      to predispose for severe allergic reactions. Finally, it provides an opportunity
      to summarize the applications of flow cytometry-assisted analysis and
      quantification of in vitro activated basophils in the diagnostic approach of
      anaphylaxis from food.

PMID- 17496426
TI  - Significance of molecular signaling for protein translation control in
      neurodegenerative diseases.
AB  - It has long been known that protein synthesis is inhibited in neurological
      disorders. Protein synthesis includes protein transcription and translation.
      While many studies about protein transcription have been done in the last decade,
      we are just starting to understand more about the impact of protein translation.
      Protein translation control can be accomplished at the initiation or elongation
      steps. In this review, we will focus on translation control at initiation.
      Neurons have long neurites in which proteins have to be transported from the cell
      body to the end of the neurite. Since supply of proteins cannot meet the need of
      neuronal activity at the spine, protein locally translated at the spine will be a
      good solution to replace the turnover of proteins. Therefore, local protein
      translation is an important mechanism to maintain normal neuronal functions. In
      this notion, we have to separate the concept of global and local protein
      translation control. Both global and local protein translation control modulate
      normal neuronal functions from development to cognitive functions. Increasing
      lines of evidence show that they also play significant roles in neurodegenerative
      diseases, e.g. neuronal apoptosis, synaptic degeneration and autophagy. We
      summarize all the evidence in this review and focus on the control at initiation.
      The new live-cell imaging technology together with photoconvertible fluorescent
      probes allows us to investigate newly translated proteins in situ. Protein
      translation control is another line to modulate neuronal function in neuron
      neuron communication as well as in response to stress in neurodegenerative
      diseases.

PMID- 17496427
TI  - Paul Ehrlich no end: antibodies as therapeutic molecules.

PMID- 17496428
TI  - Bispecific antibodies: molecules that enable novel therapeutic strategies.
AB  - Bispecific antibodies are unique in the sense that they can bind simultaneously
      two different antigens. This property enables the development of therapeutic
      strategies that are not possible with conventional monoclonal antibodies. The
      large panel of imaginative bispecific antibody formats that has been developed
      reflects the strong interest for these molecules. Although in many cases the
      manufacturing of clinical grade material remains challenging, several bispecific
      antibody formats are currently in clinical trials.

PMID- 17496429
TI  - Nuclear expression of phosphorylated EGFR is associated with poor prognosis of
      patients with esophageal squamous cell carcinoma.
AB  - OBJECTIVES: Although it has been reported that epidermal growth factor receptor
      (EGFR) is able to translocate from the plasma membrane to the nucleus, the
      pathophysiological role of this translocation in tumorigenicity is still unclear.
      In the present study, to elucidate the pathophysiological significance of EGFR
      translocation, we investigated the expression not only of conventional EGFR but
      also its phosphorylated form (pEGFR), focusing on its cellular localization in
      esophageal cancer tissues. METHODS: Fifty-two specimens of esophageal squamous
      cell carcinoma (SCC) obtained by surgery were examined immunohistochemically for
      their EGFR and pEGFR immunostaining patterns. The relationships between
      clinicopathological parameters and EGFR or pEGFR immunostaining patterns were
      then analyzed. RESULTS: In 37 (71.2%) of the 52 esophageal SCCs, EGFR
      immunoreactivity was clearly localized at the plasma membrane of the cancer
      cells, whereas pEGFR immunoreactivity was clearly localized in the nucleus in 19
      (36.5%) cases. Nuclear expression of pEGFR significantly correlated with TNM
      stage and lymph node metastasis, and moreover was associated with a poor outcome
      of esophageal SCC. CONCLUSIONS: Nuclear translocalization of pEGFR is associated
      with an increase in the malignant potential of esophageal SCC and may affect
      prognosis in patients with esophageal SCC.

PMID- 17496430
TI  - Retinoblastoma protein prevents staurosporine-induced cell death in a
      retinoblastoma-defective human glioma cell line.
AB  - OBJECTIVE: To investigate the mechanism of staurosporine-induced glioma cell
      death and cell cycle arrest using adenovirus-mediated gene transfection, as well
      as the function of retinoblastoma (Rb) and genetic instability induced by
      staurosporine. METHODS: Cell cycle regulation, cell death and nuclear
      abnormalities induced by staurosporine were examined using an adenovirus vector
      expressing Rb, p16 or p21 genes in human glioma cell lines. RESULTS: The Rb
      defective SF-539 cell line was resistant to staurosporine compared with cell
      lines expressing intact Rb. SF-539 glioma cells exposed to staurosporine became
      multinucleated and then died. Multinucleation was prevented in SF-539 cells
      transfected with the Rb gene, thus decreasing the death rate of these cells.
      CONCLUSIONS: These results imply that enforced Rb expression protects cells from
      genomic instability induced by staurosporine regardless of its upstream molecular
      effects.

PMID- 17496431
TI  - Heterogeneous expression of claudin-4 in human colorectal cancer: decreased
      claudin-4 expression at the invasive front correlates cancer invasion and
      metastasis.
AB  - OBJECTIVE: Claudin-4 plays a key role in constructing the tight junction (TJ),
      and altered claudin-4 expression has been documented in various human
      malignancies; however, little is known about the biological significance of
      claudin-4 in colorectal cancers (CRCs). The aim of this study is to investigate
      the significance of claudin-4 expression in CRC and its association with
      clinicopathological factors. METHODS: The levels of claudin-4 expression in a
      total of 129 CRCs and 44 metastatic tumors were examined by immunohistochemistry.
      A small interfering RNA (siRNA)-mediated claudin-4 knockdown examination was also
      conducted to assess the biological role(s) of claudin-4 in cultured cells.
      RESULTS: Expression of claudin-4 at the intercellular membrane was well preserved
      at the surface of the tumor; however, decreased claudin-4 expression was detected
      in 57% of CRCs, particularly at the invasive front. Interestingly, decreased
      claudin-4 expression was detected in metastatic lesions of CRC. The siRNA
      mediated claudin-4 knockdown in SW480 claudin-4-positive CRC cells upregulated
      cell motility, whereas no significant change was detected in cell proliferation.
      CONCLUSIONS: These observations suggested that disruption of claudin-4-mediated
      TJ construction enhances cancer cell invasion and metastasis in human CRC.
      Claudin-4 might be a good biomarker for diagnosing the risk of distant
      metastasis.

PMID- 17496432
TI  - Protective effect of ischemic preconditioning against liver injury after major
      hepatectomy using the intermittent pringle maneuver in swine.
AB  - OBJECTIVE: To investigate whether ischemic preconditioning (IP) protects the
      liver against ischemia-reperfusion injury (I/R-I) after major hepatectomy through
      intermittent hepatic pedicle clamping (IC) in a swine liver resection model.
      BACKGROUND: Although many studies have reported a protective effect of IP against
      continuous hepatic ischemia, it has not been elucidated whether IP protects the
      liver against I/R-I after hepatectomy using IC. This is the first study to
      evaluate the effect of IP in a swine major hepatectomy model using IC. METHODS:
      Pigs (n = 12) were divided into 2 groups (IP or non-IP). In the IP group, livers
      were subjected to IP (10 min ischemia and 10 min reperfusion) before liver
      resection using IC (15 min ischemia and 5 min reperfusion). A left
      hemihepatectomy was then performed using IC in both groups. Hemodynamic changes
      and plasma concentrations of aspartate aminotransferase, lactate dehydrogenase,
      lactic acid and hyaluronic acid were measured at 60, 120 and 180 min after
      hepatectomy. Apoptosis (TUNEL staining and electron microscopy), plasma tumor
      necrosis factor-alpha (TNF-alpha) and NO(2)(-)/NO(3)(-) were evaluated for 180
      min after hepatectomy. RESULTS: There were no significant differences in body
      weight, blood loss, resected liver weight, Pringle time or hemodynamic changes
      between the 2 groups. IP significantly reduced plasma aspartate aminotransferase
      levels for 180 min after hepatectomy (IP: 135.8 +/- 13.5 vs. non-IP: 199 +/- 16.8
      IU/l; p = 0.018). In the non-IP group, apoptotic changes in sinusoidal
      endothelial cells were observed with increased plasma TNF-alpha levels. IP
      protected liver injury from increase in plasma TNF-alpha (p = 0.042).
      Significantly fewer apoptotic cells were seen in the IP than in the non-IP group
      (p = 0.002). Plasma levels of lactate dehydrogenase, lactic acid and NO(2)(
      )/NO(3)(-) in the IP group tended to be lower than those in the non-IP group.
      CONCLUSIONS: IP prior to hepatectomy with IC resulted in less hepatic injury and
      apoptotic cell death than in livers not subjected to IP. IP with IC has the
      potential to improve the clinical postoperative course of patients undergoing
      hepatectomy.

PMID- 17496433
TI  - Reactivity of synthetic SAG1 (p30) peptide sequences with RH, S273 and Beverley
      strain-induced anti-Toxoplasma gondii antibodies.
AB  - OBJECTIVES: We compared the reactivity of IgG1 and IgG2a antibodies in mouse sera
      after infection with virulent RH and low-virulent S273 and Beverley strains of
      Toxoplasma gondii against RH SAG1 recombinant p30 (rp30) and synthetic SAG1
      peptides. METHODS: Infected mouse serum samples were collected 9 days after
      infection, and the level of total IgG, IgG1 and IgG2a against the RH SAG1 rp30
      protein and twenty peptides of the RH SAG1 protein were assessed. The
      glycosylphosphatidylinositol (GPI) modification site, the hydrophilic-hydrophobic
      structure, the transmembrane region and the secondary structure of the SAG1
      sequence of virulent and low-virulent strains were analyzed using software.
      RESULTS: The virulent strain-infected mice produced a higher level of IgG1 but a
      lower IgG2a against the rp30 antigen, while the low-virulent strain-infected mice
      produced a higher level of IgG2a than the virulent strain. The difference in the
      secondary structure of SAG1 protein between the virulent and low-virulent strain
      was largely confined to amino acid positions 291-336, showing mutations and GPI
      anchor site. CONCLUSION: The difference in the reactivity of IgG against the rp30
      antigen and synthetic peptides between virulent and low-virulent strains points
      to the importance of the primary and secondary structure assumed by antigens in
      the activation of Th cells and, subsequently, in the induction of IgG and its
      subclasses.

PMID- 17496434
TI  - PPAR ligands: are they potential agents for cardiovascular disorders?
AB  - Peroxisome proliferator activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors. The PPAR
      subfamily consists of three members: PPARalpha, PPARgamma, and PPARbeta/delta.
      Fibrates are acting via PPARalpha, and they are used as lipid-lowering agents.
      PPARgamma agonists reduce insulin resistance and have been used in the treatment
      of type 2 diabetes. As the knowledge of the pleiotropic effects of these agents
      advances, further potential indications are being revealed, including a novel
      role in the management of cardiovascular disorders (CVD). PPARalpha/gamma dual
      agonists are currently under development and hold considerable promise in the
      management of type 2 diabetes and provide an effective therapeutic option for
      treating the multifactorial components of CVD. Several experimental and clinical
      evidences elucidated the beneficial effects of PPAR ligands in prevention and
      treatment of various CVD. However, PPARalpha and PPARgamma agonists have been
      shown to be proinflammatory and proatherogenic in a few studies. Further,
      PPARgamma ligands have been noted to be involved in the pathogenesis of
      congestive heart failure. These controversial results obtained from a few studies
      created further complication in understanding the role of PPARs. The function of
      PPARdelta and its potential as a cardiovascular therapeutic target are currently
      under investigation. The present review focuses on the merits and limitations of
      PPAR agonists with regard to their use in CVD.

PMID- 17496435
TI  - Sodium nitroprusside regulates mRNA expressions of LTC4 synthesis enzymes in
      hepatic ischemia/reperfusion injury rats via NF-kappaB signaling pathway.
AB  - Leukotriene (LT) C4 (LTC4) synthesis enzymes including LTC4 synthase (LTC4S),
      microsomal glutathione S-transferase (MGST) 2 and MGST3 can all conjugate LTA4
      and reduced glutathione (GSH) to form LTC4, which is related to hepatic
      ischemia/reperfusion (I/R) injury. The relationship between nitric oxide (NO) and
      cysteinyl LTs has been shown in previous studies. However, the mechanisms of NO
      action on gene expression of LTC4 synthesis enzymes are still largely unclear
      during hepatic I/R. Adult male Sprague-Dawley rats were divided into 5 groups: a
      sham group (control), an I/R group, and sodium nitroprusside (SNP, 2.5, 5 and 10
      microg/kg/min)+I/R groups. Livers were subjected to 60 min of partial hepatic
      ischemia followed by 5 h of reperfusion, saline or SNP (2.5, 5 and 10
      microg/kg/min) administered intravenously. The mRNA levels of LTC4 synthesis
      enzymes, inducible NO synthase (iNOS) and endothelial No synthase (eNOS) in rat
      liver tissue were examined by RT-PCR; the protein expressions of NF-kappaB p65,
      p50 and IkappaBalpha in liver cell lysates and nuclear extracts were detected by
      Western blot analysis, and serum NO2. levels were also evaluated. Serum NO2.
      levels, the protein expressions of NF-kappaB p65 and p50 in the nucleus extract,
      and hepatic mRNA expressions of LTC4S and iNOS were decreased while hepatic mRNA
      of eNOS was increased in the SNP (5 and 10 microg/kg/min)+I/R groups when
      compared with those in the I/R group. SNP (2.5 microg/kg/min) promoted the mRNA
      expressions of both MGST2 and MGST3, whereas SNP (10 microg/kg/min) increased
      MGST2 mRNA but decreased MGST3 mRNA compared to those in I/R group. Compared with
      control, the mRNA expression of MGST2 and MGST3 were elevated in SNP (2.5
      microg/kg/min)+I/R group, MGST3 mRNA was significantly declined in the SNP (5 and
      10 microg/kg/min)+I/R groups. Immunohistochemistry staining revealed that I/R
      liver exhibited strong cytoplasmic and nuclear staining for NF-kappaB p65, but
      the livers of the SNP (2.5 microg/kg/min)+I/R group presented slight cytoplasmic
      and nuclear staining. But IkappaBalpha protein in all groups remains unchanged.
      It was concluded that SNP downregulated LTC4S mRNA expression by inhibiting NF
      kappaB activation independent of IkappaBalpha, but appeared to have a dual
      influence on the mRNA expressions of MGST2 and MGST3 by other signaling pathways
      during hepatic I/R injury.

PMID- 17496436
TI  - Effects of AIT-082, a purine derivative, on tremor induced by arecoline or
      oxotremorine in mice.
AB  - The effects of AIT-082, a hypoxanthine derivative, on tremor in mice were
      investigated. The mice received intragastric administration of AIT-082 for
      consecutive 60 days at doses of 150, 300 and 600 mg.kg(-1). The results showed
      that AIT-082 not only effectively inhibited the tremor induced by arecoline or
      oxotremorine, but also alleviated the tremor intensity and significantly
      shortened the tremor durations. The inhibition of tremor was perhaps associated
      with the central cholinergic nerve depressant effects as well as the stimulation
      of proliferation and differentiation of nerve cells.

PMID- 17496437
TI  - [TP53 mutations and molecular epidemiology].
AB  - Tumor suppressor p53 protein is activated by a variety of cellular stresses
      through several pathways and transactivates its downstream genes, including
      regulators of cell cycle, apoptosis and DNA repair. The loss of p53 function by
      TP53 gene mutations therefore fails to activate these genes and is thought to be
      a critical cause of carcinogenesis and/or tumor progression. TP53 is one of the
      most frequently mutated genes in human cancer. TP53 mutations are found in about
      50% of human cancers, although the frequency of TP53 mutations differs among
      tumor types. However, the degree of functional disorder of mutant p53 varies
      according to the type of TP53 mutation. And the effects of p53 on cancer
      formation and/or progression are influenced by the degree of p53 dysfunction. So
      it is important to analyze the effects of TP53 mutations carefully according to
      the oncogenicity of each mutation from the molecular epidemiological point of
      view. Here, together with some cautions needed for analyzing and interpreting the
      significance of TP53 gene mutations, we present some examples of the identified
      specific mutation spectrum and the correlation between the prognosis and TP53
      mutation in some cancers.

PMID- 17496438
TI  - [The differences of standard therapy for breast cancer between Europe/America and
      Japan--chemotherapy, operation,and radiotherapy].
AB  - As increased incidence of breast cancer, the concept of standard therapy based on
      the evidence based medicine (EBM) has been widely applied to breast cancer
      treatment in Japan. Since the major parts of evidences are common in Western
      countries and Japan,general treatment strategy for standard care seems to be
      identical in both countries. However, there are still some differences due to the
      limited usages of anti-cancer drugs and supporting drugs. We would discuss about
      these issues in this paper.

PMID- 17496439
TI  - [Comparisons of standard treatments for colorectal cancer between Japan and
      Western Countries].
AB  - In order to distinguish the differences in standard treatment for colorectal
      cancer between Japan and Western countries, we compared several issues in
      clinical practice guidelines (guidance) of Japan, the United States and the
      United Kingdom. Endoscopic resection is not common in Western countries, so its
      feasibility and efficacy should be determined in Japan. Laparoscopic resection,
      however, is applied to more advanced diseases. Expansion of the indication is now
      also under consideration in Japan a waiting the results from clinical trials.
      Although with chmeotherapy for advanced or metastatic diseases, the use of
      molecular targeting agents is recommended in the United States, it is not in the
      United Kingdom mainly because it is not cost-effective. The indication of
      adjuvant chemotherapy is similar in Japan and Western countries. Patients with
      Stage III disease and high-risk Stage II are good candidates for adjuvant
      chemotherapy. Enrollment in clinical trial should be considered for remaining
      Stage II patients. Surgery is considered to be the major treatment modality in
      Japan for the treatment of liver and lung metastases and advanced rectal cancer.
      However, neo-adjuvant chemo (-radio) therapy is considered to be the standard
      treatment in Western countries. Development of a new treatment modality for
      colorectal cancer has progressed very rapidly, and the standard treatment has
      changed dramatically. While guidelines should be revised frequently according to
      new evidence, the standard treatment must be cautiously determined based on cost
      effectiveness.

PMID- 17496440
TI  - [Comparison the standard therapies of gastric cancer in Japan with those in the
      West].
AB  - We compare Japanese practice guidelines for gastric cancer with those published
      from National Comprehensive Cancer Network (NCCN). In surgery, D1 dissection is
      referred as standard in NCCN, because mortality of D2 dissection was higher than
      that of D1 (10% vs 4%). However, Japanese investigators show lower mortality rate
      (0.8%) of D2 dissection, so D2 dissection is referred as standard for stage
      II/III disease in Japan. Chemoradiotherapy is chosen for residual disease or
      unresectable disease (M0) in NCCN, but these categories are required D2
      dissection or extensive resection in Japan. Because Japanese D2 dissection has
      better optimized survival rate than chemoradiotherapy,chemoradiotherapy will not
      be introduced to Japan. In chemotherapy, ECF or taxanes (e.g., DCF) is referred
      as a prior therapy in NCCN, but 5-FU contain regimen (e.g., FP, LV/5-FU, S-1, or
      S-1/CDDP) as a prior therapy in Japan. Both ECF and DCF are too toxic regimen for
      Japanese patient to use. Difference of race seem to be relevant to difference of
      mortality or toxicities. From the results of ACTS-GC, we think that adjuvant
      chemotherapy is referred as standard in Japan. Future, results of JCOG 9912 and
      many other trials will be coming soon, so the guidelines will be changed.

PMID- 17496441
TI  - [Differences in the therapeutic strategies for lung cancer between Europe/United
      States and Japan].
AB  - Lung cancer is a leading cause of malignancy-related death worldwide. Recently,
      therapeutic strategies for lung cancer have dramatically progressed, and attempts
      have been made to standardize the therapy for lung cancer. Because the disease
      prevalence and the susceptibility to the drugs differ with the circumstances,
      such as lifestyle, and genetic background, and ethnicity, the standard
      therapeutic strategies for lung cancer may differ with the individual country or
      region. Actually, the EGFR tyrosine kinase inhibitor, gefitinib, is well known to
      be significantly effective for oriental people, including Japanese, female,
      adenocarcinoma and never-smoker, suggesting an inherited difference. Here we
      describe not only the standard therapeutic strategies but also the difference in
      therapeutic strategies for lung cancer between Europe/United States and Japan.

PMID- 17496442
TI  - [The standard treatments for patients with hematological malignancies in Japan].
AB  - Recently, the standard treatments for hematological malignancies have shown
      dramatic improvement. For chronic myeloid leukemia, imatinib has become the
      treatment of choice in initial treatment, and its long-term effectiveness and
      safety have been confirmed. For acute myelogenous leukemia, cytarabine with
      anthracycline agent is believed to be the standard treatment in first remission
      induction therapy. To improve the efficacy of the first remission induction
      chemotherapy, the addition of gemutuzumab ozogamicin has been investigated
      intensively all over the world. However, there are many obstacles to conducting
      its clinical trial in Japan. The addition of rituximab to CHOP improves the
      survival of patients with diffuse large B-cell lymphoma. For follicular lymphoma
      patients, rituximab with conventional chemotherapies are considered the standard
      treatments, but the question of which conventional chemotherapy is better is
      unsolved. MP therapy had long been the standard treatment for elderly patients
      with multiple myeloma, but MP therapy plus thalidomide with MP therapy has been
      found to be superior. In patients who are candidates for autologous stem-cell
      transplantation, VAD therapy or high-dose dexamethasone therapy followed by
      autologous stem-cell transplantation is considered the treatment of choice. But
      the number of transplantations and the timing of second transplantation need more
      investigation. Considering the overall situation with regard to the standard
      treatments of hematological malignancies in Japan, there is little difference in
      practice from western countries. However, the framework of conducting clinical
      trials to investigate standard treatment in Japan is unsatisfactory.

PMID- 17496443
TI  - [Nedaplatin (NDP)-combination therapy (NDP/5-FU,NDP/S-1) for oral cancer].
AB  - PURPOSE: The present study evaluated the efficacy and safety of nedaplatin
      combination therapy (NDP/5-FU [5-FU arm] or NDP/S-1 [S-1 arm] ) for the treatment
      of oral squamous cell carcinoma. PATIENTS AND METHOD: Previously non-treated oral
      squamous cell carcinoma patients were eligible. Patients received 5-FU 600
      mg/m(2)iv, as a 24-hour infusion (day 1 to 5) followed by NDP 80 to 100 mg/m(2)
      iv (day 1), or S-1 60 to 80 mg/m(2) orally twice a day (day 1 to 14) followed by
      NDP 80 mg/m(2) iv (day 8) every 28 days for one or two cycles. RESULTS: In total,
      32 patients (18 in the 5-FU arm, 14 in the S-1 arm) were enrolled. Twenty
      patients were male and 12 were female. Median age was 57 years (range 20 years to
      87 years). Thirty-one patients had a performance status (PS) oF 0, and 1 patient
      had a PS 1. Three patients were stage I, 12 stage III, and 12 were stage IV. The
      overall response rate was 69% (5-FU arm,72%;S-1 arm,64%). Two patients achieved a
      complete response, 20 patients a partial response, and 10 patients had no change.
      Grade 3 leucopenia, grade 3 and 4 thrombocytopenia and liver injury occurred in
      6% (one in the 5-FU arm, and one in the S-1 arm), 9% (two in the 5-FU arm, and
      one in the S-1 arm), and 3% (one in the 5-FU arm), respectively. No other severe
      toxicities were observed. RESULTS: Response rate and toxicities were similar in
      both arms. However, the psychosocial stress on patients in the S-1 arm was
      reduced compared to that in the 5-FU arm, which required hospitalization for a
      longer period. The outcome in the present study needs further investigation.

PMID- 17496444
TI  - [Clinical evaluation of palliative chemotherapy with S-1 for oral cancer
      patients].
AB  - The purpose of this study was to investigate the effectiveness and safety of
      palliative chemotherapy using S-1. We treated 19 advanced oral SCC patients
      including 8 men and 11 women with S-1. Of the 19 patients studied, two patients
      were classified as UICC Stage II, two patients as Stage III, 14 patients as Stage
      IV A, and one patient was classified as StageIV C. The ages varied from 54 to 9 1
      years (mean ages; 78.3 years-old). The patients received this chemotherapy (80
      120 mg/day) consisting of 2 weeks' administration including 5-days'
      administration and 2-days' termination (named 'Weekday-on/Weekend-off
      administration schedule' ) following 1 week rest. After this treatment, 7 CR and
      4 PR were achieved, but the toxicities were only anorexia, leukopenia,
      thrombocytopenia, and uritication of NCI-CTC grade 1. The prognosis of 19 cases
      was 7 terminal by primary disease, 3 terminal by other disease, 7 lives with
      tumor bearing, and 2 lives without tumor bearing. We concluded that our novel S-1
      administration method was extremely effective for oral SCC, including lymph node
      metastasis, providing high potential without any severe adverse effects for
      palliative therapy.

PMID- 17496445
TI  - [A feasible study of docetaxel/nedaplatin combined chemotherapy for relapsed or
      refractory esophageal cancer patients as a 2nd-line chemotherapy].
AB  - As a 2nd-line treatment for relapsed or refractory esophageal cancer patients
      after chemoradiotherapy, we performed a combination chemotherapy of DOC/CDGP for
      11 patients. Intravenous drip infusion of DOC 30 mg/m(2)and CDGP 30 mg/m(2)on
      days 1, 8 and 15, and 4 weeks treatment was assumed as 1 cycle. We treated 8 of
      11 patients with more than 2 cycles, and 4 of 8 patients were treated with
      radiation therapy (RT). The effects by RECIST revealed partial response (PR) in 2
      patients (50%), stable disease (SD) in 1 patient and progress disease (PD) in 1
      patient without RT, and PR in 3 patients and not effective in 1 patient with RT,
      respectively. There was no treatment-related death nor adverse event of grade 4.
      The Hematological toxicities of leukopenia of grade 3 were observed in 3
      patients. Non-hematological toxicites more than grade 3 were not observed. The
      combination chemotherapy of DOC/CDGP was concluded to be safe and effective for
      relapsed or refractory esophageal cancer patients as a 2nd line treatment.

PMID- 17496446
TI  - [Clinical study of low-dose cisplatin and 5-fluorouracil chemotherapy via
      implanted fusion port in 20 patients with advanced hepatocellular carcinoma with
      portal vein tumor thrombosis].
AB  - We experienced 20 cases of advanced hepatocellular carcinoma with portal vein
      tumor thrombosis treated with low-dose cisplatin and 5-fluorouracil (5-FU)
      chemotherapy via implanted fusion port between August 1999 and September 2003. A
      fusion port was implanted by inserting an intraarterial catheter into the hepatic
      artery. Cisplatin (10 mg/day, 5 times/week, 4 weeks) and 5-FU (250 mg/day, 5
      times/week, 4 weeks) were administered for one cycle. The treatment was performed
      repeatedly until the patient showed progressive disease (PD) with an off period
      of 4 to 12 weeks. The average number of cycles was 1.7+/-0.73. Responses were
      complete response (CR) 0/20, partial response (PR) 6/20, no change (NC) 8/20, and
      PD 6/20, and the overall response rate was 30%. The 1-year survival rate was
      48.5%, and the average observation period was 357 days. The toxicities of grade 3
      and above were leukocytopenia (2 cases; 10%), thrombocytopenia (2 cases; 10%),
      nausea (1 case; 5%), and epigastralgia (1 case; 5%). Complications with reservoir
      implantation included 2 cases of catheter dislocation, 1 case of wound
      separation,1 case of bleeding from the port implantation site, 1 case of
      development of collateral circulation,and 1 case of catheter occlusion. The
      outcomes were survival in 5 cases (25%) and death in 15 cases (75%). The causes
      of death included cancer (12 cases; 60%), varices rupture (2 cases; 10%),and
      hemoptysis (1 case; 5%). The group with a CLIP score of 3 or less showed a
      significantly higher survival rate than the group with a CLIP score of 4 or more
      (survival rates were 80% and 12.5%, respectively; p=0.0032, logrank test). Among
      CLIP score factors, tumor morphology (TM) was particularly related to life
      convalescence,and TM 1 group with the tumor occupying less than half of the liver
      showed a significantly higher survival rate than the TM 2 group with the tumor
      occupying more than half of the liver (p=0.0003, logrank test) with one-year
      survival rates of 88.9% and 10.9%, respectively. CLIP score and TM were also
      significantly reflected in life convalescence on multivariate analysis. While low
      dose cisplatin and 5-FU chemotherapy via an implanted fusion port were regarded
      as a useful therapeutic regimen to improve life convalescence for cases of
      progressive hepatocellular carcinoma with portal vein tumor thrombosis (Vp 3/4),
      life convalescence in those with a CLIP score of 3 and above,particularly in the
      TM 2 group, was poor. We consider that treatment in such cases should be decided
      carefully, taking into consideration their quality of life.

PMID- 17496447
TI  - [Clinical evaluation of lung cancer patients with only best supportive care].
AB  - Eighteen cases with only symptomatically treated lung cancer admitted to our
      hospital from May 2002 to October 2006 were retrospectively investigated
      clinically. The patients consisted of 10 males and 8 females, aged 50-9 8 years
      old (mean age 78.1 yo). Clinical stage distribution revealed a higher incidence
      in the advanced stages. The performance status according to the ECOG
      classification was predominantly grade 2-4. The average survival time was 5.9 4
      months. The cell type was the major prognosticator followed by clinical stage and
      age. There was a tendency to die early in any case that had a poor whole-body
      state, such as weight reduction and a feeling of whole body fatigue. There was a
      tendency for the at home period to be short in cases that required control of
      pleural effusion, and the survival period was short.

PMID- 17496448
TI  - [Clinical study of combination chemotherapy of methotrexate, epirubicin and
      nedaplatin (MEN) in patients with advanced urothelial carcinoma].
AB  - The toxicity of platinum-based chemotherapies is a common problem for patients
      with advanced urothelial carcinoma. We performed a prospective study to assess
      the efficacy and safety of the combination chemotherapy of methotrexate,
      epirubicin and nedaplatin (MEN) as first-line treatment in patients with advanced
      urothelial carcinoma. Eligible patients had pathologically proven measurable
      unresectable or metastatic urothelial carcinoma. Between February 2003 and
      February 2006, 11 patients with a mean age of 70 years were treated every 3 weeks
      with methotrexate (30 mg/m(2) on day 1) and epirubicin (50 mg/m(2) on day 1) and
      nedaplatin (80 mg/m(2) on day 2). A median of 2.6 cycles were administered. None
      of the 11 patients achieved a complete response (CR), but 6 patients (55%)
      achieved a partial response (PR) with a median duration of response of 10 months,
      and no responses occurred in 4 patients. The median survival time was 11 months.
      Grade 4 hematological toxicities included neutropenia in 1 case (9%),
      thrombocytopenia in 2 cases (19%) and anemia in 1 case (9%). None of the 11
      patients had febrile neutropenic episodes, and no toxic death was observed. Our
      results suggest that the combination chemotherapy of methotrexate, epirubicin and
      nedaplatin (MEN) was effective and acceptable treatment in patients with advanced
      urothelial carcinoma.

PMID- 17496449
TI  - [A case of advanced oral squamous cell carcinoma responding to concurrent
      radiotherapy with S-1].
AB  - A 68-year-old patient with advanced oral squamous cell carcinoma (T3N2bM0, Stage
      IVA) was treated by concurrent radiotherapy with S-1.S-1 (120 mg/body/day) was
      orally administered for 4 weeks followed by a 2-week rest period as one course,
      and radiation was given (1.8 Gy/day; 5 days/week) for a total of 61.2 Gy. After
      61.2 Gy radiation and two courses of S-1, the primary region showed a complete
      response (CR), and that the tumor cell was not identified as a result of biopsy.
      In addition, the metastatic lymph nodes in the neck were no longer seen on head
      and neck computed tomography (CT). Although the patient is still taking UFT, he
      is well with no signs of recurrence 27 months from the initial treatment.

PMID- 17496450
TI  - [A case of maxillary sinus carcinoma showing long time survival after lung
      metastasis with administration of S-1 as tumor dormancy therapy].
AB  - The patient is a 65-year-old man, who underwent curative resection for maxillary
      sinus carcinoma after chemoradiation. Lung metastases were observed two months
      following resection, and were treated with S-1 at a dose of 120 mg/day. One
      course of the S-1 administration regimen consisted of 2 weeks and a 1-week
      interval. The patient achieved long survival for 527 days with no adverse
      reaction. Therefore, this treatment on an outpatient basis greatly contributed to
      his quality of life. We consider S-1 as a first-line anti-cancer drug for tumor
      dormancy therapy.

PMID- 17496451
TI  - [An advanced aged case of intrapulmonary metastasis of non-small cell lung cancer
      successfully controlled with S-1 capsule therapy alone for an extended period].
AB  - The patient was an 84-year-old male. About 7 months after surgery for a non-small
      cell lung cancer StageIII B, granular shadows were noted on his bilateral lungs
      on CT; and the level of CA 19-9 , a tumor marker, had increased. These findings
      led to a diagnosis of intrapulmonary tumor metastasis. Treatment with a platinum
      based antineoplastic agent was recommended,but the patient refused it because of
      his age. The patient was thus placed under observation. Because the tumor
      appeared to increase in size, treatment was initiated using S-1 capsules
      (hereafter abbreviated to S-1) alone. Each course consisted of S-1 at a dosage of
      100 mg/body/day, twice daily for 21 days, followed by 14 days of drug withdrawal.
      After the completion of one course, the level of the tumor marker was reduced to
      normal. After 6 courses were completed, CT indicated a marked reduction or
      elimination of the intrapulmonary metastatic foci. Malignant phenomenon exceeding
      grade 3 was no longer recognized,and it was possible to deliver the scheduled
      dosage of S-1 throughout the entire series of courses. At the end of the 14th
      course, no signs of exacerbation or recurrence were recognized. It has been about
      18 months after the S-1 single therapy was started. This therapy is still being
      continued.

PMID- 17496452
TI  - [A case of postoperative multiple pulmonary metastases of non-small-cell lung
      cancer successfully treated with S-1].
AB  - We report a case of postoperative multiple pulmonary metastases of NSCLC
      successfully treated with S-1. A 72-year-old man underwent rt. lower lobectomy +
      ND 2 a by VATS. The histopathological examination showed squamous cell carcinoma,
      pT4 (satellite nodules in same lobe) N0M0. Multiple pulmonary metastases appeared
      3 months after operation. We started combination chemotherapy with S-1 and CBDCA.
      S-1 (100 mg/body) was administered on days 1-21. CBDCA (AUC=5.0) was administered
      on day 8. Multiple pulmonary metastases almost disappeared after 2 courses of
      combination chemotherapy. After 6 courses of combination chemotherapy with S-1
      and CBDCA, we then converted to S-1 only. Every cycle was repeated every 5 weeks.
      One year later, there was no sign of disease progression. S-1 is considered to be
      effective and safely administered in patients with NSCLC.

PMID- 17496453
TI  - [A case of liver metastasis of gastric cancer undergoing non-curative operation
      responding completely to combination therapy of S-1 and CDDP].
AB  - We experienced a case with liver metastasis of gastric cancer that disappeared by
      S-1 administration following non-curative operation. A distal gastrectomy for
      advanced gastric cancer with liver metastasis was performed on a 71-year-old
      male. S-1 was administered at 100 mg/body/day for 4 weeks followed by withdrawal
      for 2 weeks, and CDDP was prescribed at 5 mg/body/day div, for 2 days per a week
      as 1 course. After one course of treatment, the liver metastatic lesion decreased
      in size (reduction ratio was 87.4%). For side effect, S-1 100 mg alone was
      administered beginning with the second course. This lesion became CR after four
      courses. The adverse events of grade 3 observed during S-1 administration were
      neutropenia and diarrhea. We changed S-1 to UFT after nine courses, and the
      patient has now survived 1 year without recurrence after the disappearance of
      liver metastasis.

PMID- 17496454
TI  - [Two patients with StageIV gastric cancer responding to combination therapy with
      S-1 and low-dose CDDP after reduction surgery].
AB  - Two patients with advanced gastric cancer who underwent gastrectomy and
      pathological examination were both diagnosed as having Stage IV gastric cancer
      with distant lymph-node metastases and peritoneal dissemination, respectively.
      The patients received S-1 and low-dose CDDP in combination therapy after
      reduction surgery. Each treatment course consisted of S-1 100 mg/body oral
      administration for 3 weeks and intravenous administration of CDDP at a dose of 25
      mg/m(2) on days 7, 14 and 21. The course repeated after a two-week rest period,
      and the treatment was repeated every five weeks. After three courses of
      treatment, both patients received S-1 100 mg/body for 2 weeks on and 2 weeks off
      as long as possible. They remain alive 15 and 12 months after initial treatment,
      respectively, without any sign of recurrence. The patients did not experience
      grade 3 or more adverse events and received this regimen as an outpatient. These
      results suggest that combination therapy with S-1 and low-dose CDDP is effective
      against advanced gastric cancer.

PMID- 17496455
TI  - [Three advanced gastric cancer patients successfully treated by combination
      therapy of paclitaxel and cisplatin].
AB  - We report 3 gastric cancer patients with peritoneal dissemination who were
      successfully treated with weekly paclitaxel and cisplatin. The patients were 2
      men and 1 woman from 57 to 70 years in age. The histological types were 2 poorly
      differentiated adenocarcinomas and 1 moderately-differentiated adenocarcinoma.
      Intravenous infusion of PTX (80 mg/m(2)) and CDDP (25 mg/m(2)) after short
      premedication was continued for 3 weeks followed by 1 week rest. Ascites improved
      only after administration of 1 course in all patients.PTX/CDDP is thought to be
      an effective chemotherapy showing acceptable toxicity against advanced gastric
      cancer with ascites.

PMID- 17496456
TI  - [A resected case of effective treatment with gemcitabine for advanced pancreatic
      cancer with peritoneal metastasis].
AB  - We report a resected case of advanced pancreatic cancer after successful
      chemotherapy. A 69-year-old man with abdominal pain was diagnosed as locally
      advanced pancreatic tail cancer with peritoneal metastasis based on computed
      tomography (CT). Preoperative serum CA 19-9 was 5,046 U/mL. In the outpatient
      setting, gemcitabine (GEM) at a dose of 1,000 mg/m(2)was administered once a week
      for 3 weeks with a 1-week rest as 1 cycle. Abdominal CT scan after 5 cycles of
      chemotherapy revealed that ascites disappeared and the tumor dramatically shrank.
      Serum CA 19-9 also dropped to 12 U/mL. Thus, we considered the patient had a
      partial response, and performed distal pancreatectomy and splenectomy with D 3
      lymph node dissection. Peritoneal seeding was not found and peritoneal washing
      cytology was negative. Histological examination of the primary lesion revealed a
      small amount of residual cancer cells. However, he died of peritoneal metastasis
      only 3 months after the operation. Surgical resection following chemotherapy
      should be performed carefully after close evaluation of the antitumor efficacy
      including residual isolated tumor cell for patients with previously distant
      metastases.

PMID- 17496457
TI  - [A case of ascending colon cancer with enlarged metastatic lymph nodes around
      superior mesenteric arterial root that responded dramatically to S-1 and CPT-11
      combination chemotherapy].
AB  - A 50-year-old man was admitted because of right lateral abdominal pain, easy
      fatigue and anemia. An endoscopic examination revealed advanced ascending colon
      cancer, and abdominal CT scan demonstrated enlarged metastatic lymph nodes of
      superior mesenteric arterial circumference. The Serum CEA rose considerably. The
      preoperative diagnosis was cStage IV (SS, N(4), P(0), H(0), M(-)), and right
      colectomy was performed on March 2, 2005. The metastatic lymph nodes around the
      superior mesenteric arterial root macroscopically remained. From the 20th
      postoperative day, we started combination chemotherapy using S-1 plus CPT-11 as
      one course for three weeks. S-1 (120 mg/body/day) was orally administered for 2
      weeks continuously, and CPT-11 (80 mg/m(2)) was done intravenously on day 1 and
      8. Serum CEA was normalized in the middle of 3 courses. Moreover, after 13
      courses, a complete response (CR) was noted on the follow-up abdominal CT scan.
      No severe side effect more than grade 2 was observed, there was no interruption
      of the dosage, and PS was sufficiently maintained kept enough through this
      combination chemotherapy. The course has been without metastasis, recurrence and
      a rise of serum CEA now in the 16th postoperative month. S-1/CPT-11 combination
      chemotherapy is a promising and effective cure for unresectable progressive
      recurrent colorectal cancer in future.

PMID- 17496458
TI  - Successfully-treated mesenteric non-Hodgkin's lymphoma involving hepatic mass--a
      case report.
AB  - A mesenteric diffuse large B-cell lymphoma which also involves the liver is very
      rare. We describe herein a mesenteric diffuse large B-cell lymphoma with hepatic
      involvement successfully treated by the combination of surgical resection and
      multiagent chemotherapy. A 77-year-old man was referred to our hospital because
      of a right lower abdominal tumor. Abdominal computed tomography showed a mass in
      the mesenterium at the ileocoecal region and multiple mass in the liver. Gallium
      scintigram showed focal hot uptake at the ileocoecal region and multiple areas of
      increased Gallium uptake in the liver. With the diagnosis of a mesenteric tumor
      with liver metastases, a laparotomy was performed. By an intraoperative
      pathological examination, non-Hodgkin's lymphoma was suggested. The mesenteric
      mass was completely resected, but additional operative procedures were not done
      to the liver. After the operation, the patient was determined to have Stage IVB
      diffuse large B-cell lymphoma, and chemotherapy based on the CHOP-like regimen
      was given. After the 8th course of such chemotherapy, he was confirmed to have
      achieved a complete remission by abdominal computed tomography and Gallium
      scintigram.The Stage IV mesenteric diffuse large B-cell lymphoma involving the
      liver seems to be an indication for combination therapy of surgical resection and
      multiagent chemotherapy.

PMID- 17496459
TI  - [Improved outcome in brain abscess during induction in acute myelocytic
      leukemia].
AB  - A 31-year-old female with acute myelocytic leukemia was admitted to our hospital
      in June 2004. She had complications of brain abscess at the WBC nadir after the
      second course of induction therapy. However,because the platelet count was low,
      neurosurgical procedures, including craniotomy/abscess resection, or abscess
      drainage, were not performed, and we could not detect bacteria or fungus as the
      cause of brain abscess. Combination therapy with meropenem trihydrate and
      fosfluconazole was effective. Thereafter, she underwent related peripheral blood
      stem cell transplantation, and has had no recurrence of brain abscess. Brain
      abscess during chemotherapy for patients with acute leukemia is commonly due to
      fungus,particularly Aspergillus, which has a very high fatality rate. Therefore,
      the treatment of brain abscess without the detection of bacteria and fungus
      requires combination therapy with antifungal agents and antibiotics. In this
      case, methionine-positron emission tomography was useful for the evaluation of
      therapeutic effectiveness for brain abscess.

PMID- 17496460
TI  - [Three cases of necrotizing pneumonia by pseudomonas aeruginosa infection in
      hematological malignancy, including dead and alive cases].
AB  - Pseudomonas aeruginosa (P. aeruginosa) is a common nosocomial pathogen that often
      causes pneumonia, especially in immunocompromised patients including cancer
      bearing-hosts. In cancer patients who have great risk of gram-negative bacteria
      leading to fatal infection, P. aeruginosa bacteremia easily results in septicemia
      with shock and life-threatening complications such as vital organ failure. Among
      those complications, necrotizing pneumonia is an infectious disease of lung
      caused by P. aeruginosa characterized by rapid cavitation and progressive
      clinical course, which is fatal not only in cancer patients but also in healthy
      hosts. P.aeruginosa is one of the pathogens targeted for empirical therapy
      neutropenic patients. Three case series of necrotizing pneumonia were reviewed in
      this report. All three had hematological malignancies and were immunocompromised.
      One of the three cases,a 30-year-old man with malignant lymphoma, recovered from
      pneumothorax and pyothorax complicated with lung cavitation. The other two
      patients died with a short course; a 55-year-old man with chronic myelogeneous
      leukemia within 7 hours, and a 54-year-old man with malignant lymphoma within 2
      days after the onset of pneumonia, respectively. In these 3 cases, there were no
      obvious associations between prognosis and neutrophil counts, duration of
      neutropenia and steroid administration.

PMID- 17496461
TI  - [Adjuvant chemotherapy for colorectal cancer in Japan-current state and problem
      areas].
AB  - Chemotherapy that targets metastatic colorectal cancer originally developed in
      Europe and the US, and was introduced to Japan in April, 2005, where it has since
      headed toward full scale clinical applications. This event created an opportunity
      to re-evaluate the role of postoperative adjuvant chemotherapy in Japan. In
      Europe and the US, adjuvant therapy has centered on the intravenous
      administration of leucovorin/fluorouracil, while in Japan, it has been long-term
      continuous administration of oral fluoropyrimidine preparations. Despite this
      difference in historical background,guidelines created in 2005 recommend both
      LV/5-FU and LV/UFT regimens and there has been increased application of evidence
      based adjuvant chemotherapy. The benefits of postoperative adjuvant chemotherapy
      in stage II and III (high risk of recurrence) colorectal cancer patients have
      also come to be recognized. Examination of a new survey of 100 medical
      specialists on the current state of adjuvant chemotherapy for colorectal cancer
      in Japanese clinical settings revealed that for stage III patients, there is a
      tendency to choose treatment based on evidence gathered from both home and
      abroad. In contrast, a solid majority (60%) of stage II patients are treated
      exclusively with oral fluoropyrimidine despite a lack of, or limited evidence of
      efficacy. At the same time, half of the physicians who treated stage II patients
      with adjuvant chemotherapy initially attempted to identify those with a high risk
      of cancer recurrence and treat them accordingly; which was a breakthrough in the
      clinical treatment approach. While ongoing comparative Japanese clinical studies
      that use adjuvant chemotherapy for the treatment of colorectal cancer were noted,
      consideration was also given to the desired future direction clinical research
      should take.

PMID- 17496462
TI  - Is HOMA index a predictor of nocturnal nondipping in hypertensives with newly
      diagnosed type 2 diabetes mellitus?
AB  - OBJECTIVE: Insulin resistance is involved in glucose intolerance, type 2 diabetes
      mellitus and hypertension. We aimed to analyze relationship between insulin
      resistance and nocturnal nondipping. METHODS: Patients underwent physical and
      biochemical evaluation, clinic and ambulatory blood pressure measurements. The
      homeostasis model assessment (HOMA) index was calculated. RESULTS: Ninety-six
      essential hypertensive patients, of whom 42 were dippers, with newly diagnosed
      type 2 diabetes mellitus were included. Nighttime average heart rate and mean
      arterial pressure of nondippers were higher than dippers (P<0.0001 and 0.001).
      Nondippers had higher fasting plasma glucose, serum insulin levels and HOMA
      indices than dipper patients (P=0.006, <0.0001 and <0.0001). Ten dippers and 36
      nondippers were insulin resistant (P<0.0001). Clinic (r=+0.22, P=0.031), daytime
      average (r=+0.27, P=0.007), nighttime average (r=+0.33, P=0.001), 24-h average
      systolic (r=+0.25, P=0.015) and nighttime average diastolic blood pressures
      (r=+0.31, P=0.002) were positively correlated with homeostasis model assessment
      index. Nighttime mean arterial pressure and heart rates (daytime, nighttime, 24-h
      average) showed positive correlation with homeostasis model assessment index. In
      multivariate analysis, high homeostasis model assessment index was associated
      with increased nondipping risk (odds ratio: 1.85, confidence interval: 1.24-2.76,
      P=0.003). After adjustment of several factors, average nighttime systolic
      (P<0.0001), diastolic (P<0.0001) and 24-h diastolic blood pressure (P=0.029) and
      heart rate (P=0.001) measurements of insulin resistant patients were higher than
      nonresistant patients. CONCLUSIONS: Insulin resistance is related with diurnal
      blood pressure variation. The HOMA index may be a predictor of nocturnal
      nondipping in patients with essential hypertension and newly diagnosed type 2
      diabetes mellitus.

PMID- 17496463
TI  - The effect of telmisartan and ramipril on early morning blood pressure surge: a
      pooled analysis of two randomized clinical trials.
AB  - OBJECTIVES: The period of early morning blood pressure surge is associated with a
      higher incidence of cardiovascular events than at other times of the day.
      Antihypertensive medication given once daily in the morning may not protect
      against this surge if its duration of action is too short. We compared
      telmisartan, an angiotensin II receptor blocker with a trough-to-peak ratio >90%,
      with ramipril, an angiotensin-converting enzyme inhibitor with a trough-to-peak
      ratio of around 50%. METHODS: Data from two prospective, randomized, open-label,
      blinded endpoint studies comparing telmisartan force titrated to 80 mg once daily
      and ramipril 10 mg once daily were pooled. Patients had mild-to-moderate
      hypertension and were assessed using 24-h ambulatory blood pressure monitoring at
      baseline and endpoint. Early morning blood pressure surge was defined as the
      difference between mean blood pressure within 2 h after arising and night-time
      low. Patients were grouped into quartiles according to their baseline systolic
      surge. RESULTS: Data from 1279 patients were analyzed. Telmisartan changed the
      overall mean (SE) systolic surge by -1.5 (0.47) mmHg, and ramipril by +0.3 (0.47)
      mmHg (P=0.0049). The magnitude of surge reduction was greatest in the quartile
      with highest baseline systolic surge: telmisartan -12.7 (0.91), ramipril -7.8
      (1.02) mmHg (P=0.0004). Telmisartan also reduced the surge compared with ramipril
      in dippers, but there were no differences between the two groups in nondippers.
      CONCLUSIONS: Telmisartan significantly reduced the early morning systolic blood
      pressure surge compared with ramipril. A reduction in this surge may help to
      reduce cardiovascular events in the morning period.

PMID- 17496464
TI  - Comparison of noninvasive oscillometric and intra-arterial blood pressure
      measurements in hyperacute stroke.
AB  - OBJECTIVES: This study aims to compare automatic oscillometric blood pressure
      recordings with simultaneous direct intra-arterial blood pressure measurements in
      hyperacute stroke patients to test the accuracy of oscillometric readings.
      METHODS: A total of 51 first-ever stroke patients underwent simultaneous
      noninvasive automatic oscillometric and intra-arterial blood pressure monitoring
      within 3 h of ictus. Casual blood pressure was measured in both arms using a
      standard mercury sphygmomanometer on hospital admission. Patients who received
      antihypertensive medication during the blood pressure monitoring were excluded.
      RESULTS: The estimation of systolic blood pressure (SBP) using oscillometric
      recordings underestimated direct radial artery SBP by 9.7 mmHg (95% confidence
      interval: 6.5-13.0, P<0.001). In contrast, an upward bias of 5.6 mmHg (95%
      confidence interval: 3.5-7.7, P<0.001) was documented when noninvasive diastolic
      blood pressure (DBP) recordings were compared with intra-arterial DBP recordings.
      For SBP and DBP, the Pearson correlation coefficients between noninvasive and
      intra-arterial recordings were 0.854 and 0.832, respectively. When the study
      population was stratified according to SBP bands (group A: SBP<or=160 mmHg; group
      B: SBP>160 mmHg and SBP<or=180 mmHg, group C: SBP>180 mmHg), higher mean DeltaSBP
      (intra-arterial SBP-oscillometric SBP) levels were documented in group C (+19.8
      mmHg, 95% confidence intervals: 12.2-27.4) when compared with groups B (+8.5
      mmHg, 95% confidence intervals: 2.7-14.5; P=0.025) and A (+5.9 mmHg, 95%
      confidence intervals: 1.8-9.9; P=0.002). CONCLUSION: Noninvasive automatic
      oscillometric BP measurements underestimate direct SBP recordings and
      overestimate direct DBP readings in acute stroke. The magnitude of the
      discrepancy between intra-arterial and oscillometric SBP recordings is even more
      prominent in patients with critically elevated SBP levels.

PMID- 17496465
TI  - Comparison of different methods of blood pressure measurements.
AB  - OBJECTIVE: To compare different methods of measuring and averaging blood pressure
      readings, and see how they affect classification of patients as normotensive or
      hypertensive. METHODS: The comparisons were made in up to 145 suitable patients
      in the first and last week of a 6-week surveillance. Ambulatory blood pressure
      measurements were taken from the nondominant arm, as the average of up to 78
      measurements over 24 h (24-h ambulatory blood pressure measurements), or 60 from
      0700 h to 2200 h (daytime ambulatory blood pressure measurements), or 18 from
      2200 h to 0700 h (night-time ambulatory blood pressure measurements). Office
      blood pressure measurements were taken by the outpatient department nurse in
      triplicate from both arms, and the averages were taken of the second and third of
      each triplicate. Home blood pressure measurements were taken in duplicate each
      morning and evening, entered by patients into diaries, and the available readings
      of up to four values per day were averaged for the first and sixth week. The
      classifications of normotensive versus hypertensive produced by criterion values
      of 24-h ambulatory blood pressure measurements of 125/80 and 130/80 mmHg were
      compared with the classifications produced by the other measurements with a range
      of criterion values. RESULTS: The home blood pressure measurements and office
      blood pressure measurements of systolic values underestimated the corresponding
      24-h ambulatory blood pressure measurements values by 3-9 average (SD 9-18) mmHg,
      and the diastolic values overestimated them by averages of 3-6 (SD 6-13) mmHg.
      Daytime ambulatory blood pressure measurement systolic and diastolic values
      overestimated them by 2-4 (SD 2-4) mmHg and night-time ambulatory blood pressure
      measurement values underestimated them by 7-12 (SD 5-9) mmHg. In comparing the 24
      h ambulatory blood pressure measurement classifications of hypertensives versus
      normotensives with those produced from the other types of measurements, it was
      easiest to detect criterion values for daytime ambulatory blood pressure
      measurement that gave the best agreement and they appeared different for the
      different criterion values of 24-h ambulatory blood pressure measurement. For the
      other types of measurement, the agreement was generally worse and it was harder
      to detect a best criterion value for agreement with either of the 24-h ambulatory
      blood pressure measurement classifications. A subsample of 63 patients identified
      as needing institution, maintenance or modification of antihypertensive treatment
      excluded about half of the patients classified as hypertensive by either 24-h
      ambulatory blood pressure measurement criterion. CONCLUSION: Limited agreement
      existed between different ways of classifying patients. The utility of the
      classifications depends on the purpose to which they are put.

PMID- 17496466
TI  - Measuring orthostatic hypotension with the Finometer device: is a blood pressure
      drop of one heartbeat clinically relevant?
AB  - OBJECTIVE: The role of orthostatic hypotension in falls in older people is
      generally accepted. Because of the high degree of intra- and interobserver
      variability in conventional measurements of orthostatic hypotension, application
      of continuous measurement systems has been proposed. The clinical relevance of a
      blood pressure drop lasting one heartbeat, however, is unknown. We therefore
      investigated which time average of continuous-finger-blood-pressure measurement
      (Finometer) showed the best association between orthostatic hypotension and
      falls. This was also compared with conventional sphygmomanometer measurements.
      METHODS: In 217 geriatric outpatients supine and standing (finger) blood pressure
      to diagnose orthostatic hypotension was monitored with Finometry (beat-to-beat
      and 1, 5, 10, 15, 20 and 30 s averages) and sphygmomanometry. History of fall
      incidents (previous year) was registered. RESULTS: The best association (C=0.22,
      P=0.003) with falls history was found for the 5-s average of Finometry, whereas
      falls and orthostatic hypotension assessed by sphygmomanometry did not correlate.
      The odds ratio of a fall according to orthostatic hypotension using the 5-s
      average was 2.54 (95% CI: 1.37 to 4.71). CONCLUSIONS: Orthostatic hypotension and
      falls are correlated when using Finometry, with the best association found when
      using 5-s averages. As the etiology of falls is often multifactorial, orthostatic
      hypotension and falls are poorly correlated, irrespective of the method or time
      average that is applied.

PMID- 17496467
TI  - Validation of the OMRON M7 (HEM-780-E) blood pressure measuring device in a
      population requiring large cuff use according to the International Protocol of
      the European Society of Hypertension.
AB  - BACKGROUND: A high percentage of hypertensive patients present an arm
      circumference of over 32 cm; the use of a large cuff is therefore recommended.
      Validation studies are usually performed in the general population using a
      standard-size cuff. The aim of this study was to assess the accuracy of the Omron
      M7 device in a population with an arm circumference ranging from 32 to 42 cm.
      DESIGN: A validation study was performed according to the International Protocol
      of the European Society of Hypertension. This protocol is divided into two
      phases: the first phase is performed on 15 selected participants (45 pairs of
      blood-pressure measurements); if the device passes this phase, 18 supplementary
      participants are included (54 pairs of blood-pressure measurements), making a
      total number of 33 participants (99 pairs of blood-pressure measurements), on
      whom the analysis is performed. METHODS: For each participant, four blood
      pressure measurements were performed simultaneously by two trained observers,
      using mercury sphygmomanometers fitted with a Y tube; the measurements alternated
      with three by the test device. The difference between the blood-pressure value
      given by the device and that obtained by the two observers (mean of the two
      observations) was calculated for each measure. The 99 pairs of blood-pressure
      differences were classified into three categories (<or=5, <or=10 and <or=15
      mmHg). The number of differences in each category was compared with the number
      required by the European Society of Hypertension protocol. RESULTS: The Omron M7
      device passed the first and the second phases of the validation process. The
      average differences between the two observers were 1.5+/-3.2 and -0.5+/-2.2 mmHg
      for systolic blood pressure and diastolic blood pressure, and those between the
      device and the mercury sphygmomanometer were -1.6+/-6.7 for systolic blood
      pressure and -0.12+/-4.0 mmHg for diastolic blood pressure Readings that differ
      by less than 5, 10 and 15 mmHg for systolic blood-pressure and diastolic blood
      pressure values fulfill the recommendation criteria of the European Society of
      Hypertension protocol. CONCLUSIONS: The Omron M7 (HEM-780-E) device fulfilled the
      validation criteria of the international protocol in a population with an arm
      circumference ranging from 32 to 42 cm.

PMID- 17496468
TI  - Validation of the Artsana CSI 610 automated blood pressure monitor in adults
      according to the International Protocol of the European Society of Hypertension.
AB  - BACKGROUND: There is evidence that blood pressure measurement outside the
      doctor's office can provide valuable information for the diagnostic evaluation of
      hypertensive patients and for monitoring their response to treatment. Home blood
      pressure monitoring devices have a major role in this setting, provided that
      their accuracy in measuring blood pressure is demonstrated by validation studies.
      OBJECTIVE: This study aimed at verifying whether the automatic electronic
      oscillometric blood pressure measuring device Artsana CSI 610 complied with the
      standard of accuracy indicated by the ESH International Protocol. METHODS:
      Sequential measurements of systolic and diastolic blood pressure were obtained in
      33 participants using the mercury sphygmomanometer (two observers) and the test
      device (one supervisor). A standard adult cuff was always employed during the
      study. According to the ESH validation protocol, 99 couples of test device and
      reference blood pressure measurements were obtained during the two phases of the
      study (three pairs for each of the 33 participants). RESULTS: The Artsana CSI 610
      device successfully passed phase 1 of study validation with the number of
      absolute differences between test and reference device never <35 within 5 mmHg
      and never <40 within 10 and 15 mmHg. The test device also passed phase 2 of the
      validation study with a mean (+/-SD) device-observer difference of -1.4+/-4.8
      mmHg for systolic and -0.9+/-3.5 mmHg for diastolic blood pressure. CONCLUSIONS:
      According to the results of the validation study on the basis of the ESH
      International Protocol, the Artsana CSI 610 can be recommended for clinical use
      in adults.

PMID- 17496469
TI  - Validation of the Microlife WatchBP Home device for self home blood pressure
      measurement according to the International Protocol.
AB  - OBJECTIVE: Current guidelines recommend that self monitoring of blood pressure at
      home should only be performed using validated devices. This study assessed the
      accuracy of the Microlife WatchBP Home device for self home blood pressure
      measurement according to the European Society of Hypertension International
      Protocol. METHODS: Thirty-three participants were included (15 in phase 1 and an
      additional 18 in phase 2). Simultaneous blood pressure measurements were taken by
      two observers (Y-tube-connected mercury sphygmomanometers) four times
      sequentially, with three measurements taken using the tested device. Absolute
      differences between observer and device measurements were classified into three
      zones (within 5, 10 and 15 mmHg). The number of measurements with a difference
      within 5 mmHg was calculated for each individual. RESULTS: In phase 1, the device
      produced 38, 43 and 43 measurements within 5, 10 and 15 mmHg, respectively, for
      systolic blood pressure and 35, 45 and 45 for diastolic blood pressure. In phase
      2.1, the device produced 75, 91 and 97 measurements within 5, 10 and 15 mmHg for
      systolic, and 74, 93 and 99 for diastolic blood pressure. In phase 2.2, 30
      participants had at least two of their differences within 5 mmHg and two
      participants had no differences within 5 mmHg for systolic blood pressure,
      whereas for diastolic blood pressure the number of participants were 27 and
      three, respectively. Mean difference for systolic blood pressure was -0.3+/-5.6
      mmHg and for diastolic -2.4+/-4.8 mmHg. CONCLUSIONS: The Microlife WatchBP Home
      device for self home blood pressure measurement fulfills all the validation
      criteria of the International Protocol and can, therefore, be recommended for
      clinical use in the adult population.

PMID- 17496470
TI  - The effect of crossing legs on blood pressure.
AB  - OBJECTIVE: To determine whether crossing of the legs at the knee or at the ankles
      during blood pressure measurement in sitting position has an effect on blood
      pressure. METHODS: One hundred and eleven patients, 60 women, mean age 52+/-17
      years (19-80): 49 chronically treated hypertensives, 28 treated diabetics and 34
      normotensives were measured by one trained investigator, with an oscillometric
      device (Omron 705CP) on the left arm. We looked for the difference of blood
      pressure with the ankle or the knee crossed versus the uncrossed position.
      RESULTS: Leg crossing at the knee during blood pressure measurement increased
      systolic blood pressure significantly by 6.7 (95% confidence interval 5.0-8.4)
      mmHg in the hypertensives and 7.9 (4.0-11.8) mmHg in the treated diabetics.
      Diastolic blood pressure increased by 2.3 (0.8-3.8) mmHg in the hypertensives and
      1.7 (0.1-3.4) mmHg for the treated diabetics. Normotensive participants showed a
      smaller, though significant, increase of systolic blood pressure 2.7 (1.2-4.2)
      mmHg, but not significant for diastolic blood pressure, -0.1 (-1.5-1.3) mmHg,
      respectively. In all groups there was no effect of crossing the ankles on blood
      pressure. No differences were found between men and women. No significant
      correlation between the increase of the blood pressure when the knees were
      crossed and BMI, age or baseline blood pressure was present. CONCLUSIONS: Blood
      pressure increased when legs were crossed at the knee in the sitting position. No
      significant increase of blood pressure was found when crossing the legs at the
      ankles. Leg position during measurement of blood pressure should be standardized
      and mentioned in publications.

PMID- 17496471
TI  - The effect of temperature on systolic blood pressure.
AB  - OBJECTIVES: To quantify the association between systolic blood pressure and
      season, indoor and outdoor temperature and short-term trends in outdoor
      temperature. METHODS: The study used data from the WHO MONICA Project risk
      factors surveys from 25 populations in 16 countries. Random samples of men and
      women aged 35-64 years were invited to participate. Systolic blood pressure
      measurements were available for 115 434 participants. Hierarchical models were
      used to quantify the association between blood pressure and temperature, and
      account for differences in the associations between populations. RESULTS:
      Populations closer to the equator showed larger seasonal changes in blood
      pressure. A 1 degrees C increase in indoor temperature reduced systolic blood
      pressure by an average of 0.31 mmHg (95% posterior interval: -0.44, -0.19). A 1
      degrees C increase in outdoor temperature reduced blood pressure by the smaller
      average of 0.19 mmHg (95% posterior interval: -0.26, -0.11). Increased outdoor,
      but not indoor, temperatures had a stronger effect in women than in men. The
      effect of outdoor temperature remained after controlling for indoor temperature.
      Short-term trends in temperature did not have a statistically signicant effect.
      CONCLUSIONS: Indoor and outdoor temperature have independent effects on systolic
      blood pressure, and both should be controlled for in studies that measure blood
      pressure. Improved protection against cold temperatures could lead to a reduction
      in the winter excess of cardiovascular mortality.

PMID- 17496472
TI  - Distance education in nursing: 25 years and going strong.

PMID- 17496475
TI  - Welcome to the dark side: how nurses in information systems contribute to patient
      care.

PMID- 17496476
TI  - Camtasia studio: a teaching tool for academicians and clinicians.

PMID- 17496477
TI  - Mail merge: a time-saving tool.

PMID- 17496478
TI  - Postpartum women's evaluations of an audio/video computer-assisted perinatal
      violence screen.
AB  - For universal screening to become a reality, research must first validate the
      effectiveness and acceptability of violence screening. This study describes
      postpartum women's perceptions of an anonymous computer-assisted self-interview
      for perinatal violence screening. A sample of 519 postpartum women completed
      interviews that included audio and video enhancements. Post-response evaluations
      were positive with most women, indicating that they preferred computer interviews
      to face-to-face or written abuse screening. In addition, participants indicated
      that the computer format and associated anonymity positively influenced their
      willingness to answer the violence questions truthfully. Computer interviews
      offer an alternative approach to violence screening that may help women who are
      hesitant to disclose abuse directly to their healthcare providers.

PMID- 17496479
TI  - WebQuests: a new instructional strategy for nursing education.
AB  - A WebQuest is a model or framework for designing effective Web-based
      instructional strategies featuring inquiry-oriented activities. It is an
      innovative approach to learning that is enhanced by the use of evolving
      instructional technology. WebQuests have invigorated the primary school (grades K
      through 12) educational sector around the globe, yet there is sparse evidence in
      the literature of WebQuests at the college and university levels. WebQuests are
      congruent with pedagogical approaches and cognitive activities commonly used in
      nursing education. They are simple to construct using a step-by-step approach,
      and nurse educators will find many related resources on the Internet to help them
      get started. Included in this article are a discussion of the critical attributes
      and main features of WebQuests, construction tips, recommended Web sites
      featuring essential resources, a discussion of WebQuest-related issues identified
      in the literature, and some suggestions for further research.

PMID- 17496481
TI  - Nursing outcomes classification in the systematized nomenclature of medicine
      clinical terms: a cross-mapping validation.
AB  - The Systematized Nomenclature of Medicine Clinical Terms is a reference
      terminology that can be used to cross-map standardized healthcare languages
      across healthcare disciplines. It is important to ensure that the knowledge
      represented in individual source systems has been preserved during the process of
      cross-mapping to the target system. The purpose of this study was to validate the
      cross-mapping between the Nursing Outcomes Classification and the Systematized
      Nomenclature of Medicine Clinical Terms. The methodology to detect incorrectly
      assigned (mis-assigned) concepts from the source system to the target system was
      developed by the authors. The methodology compared knowledge representations of
      Nursing Outcomes Classification concepts in both systems by using human expert
      judgments. Each concept's meaning is defined by both the structures and
      definitions in the concept model. Sixteen (4.8%) mis-assigned Nursing Outcomes
      Classification concepts in the Systematized Nomenclature of Medicine Clinical
      Terms, and one inconsistent concept representation in the Nursing Outcomes
      Classification were found. Results and recommendations were given to both the
      Nursing Outcomes Classification and Systematized Nomenclature of Medicine
      Clinical Terms developers for consideration of future system improvements.

PMID- 17496482
TI  - Development and testing of an evaluation scale of personal digital assistants.
AB  - With the increasingly popular use of PDAs in healthcare, the need for a reliable
      scale to evaluate this technology has become critical. The authors describe the
      development and testing of an evaluation scale for PDAs in nurses' daily
      practice. A review of the literature generated a 30-item questionnaire that was
      administered online to a convenience sample of 334 hospital nurses in Taiwan. The
      scale's reliability and validity were established by item and factor analyses.
      From the original pool of 30 items, 24 were selected and grouped into six major
      constructs: user preference, nursing efficiency, user training, device features,
      drug content, and user support. The scale's overall reliability (alpha
      coefficient) was 0.88. Survey results showed an overall slightly negative score
      for the evaluation scale for PDAs, indicating a slightly moderate evaluation of
      PDA use. Additional psychometric analysis and refinement of item wordings are
      recommended.

PMID- 17496483
TI  - Survey demonstrates importance of nurse informaticist role in health information
      technology design and implementation.

PMID- 17496484
TI  - Care transformation and the promise of health information technology: a nursing
      perspective.

PMID- 17496486
TI  - Impaired ventricular electrical stability and sympathetic hyperactivity in
      patients with multivessel coronary artery disease.
AB  - OBJECTIVES: The extent of atherosclerotic disease is identified as one of the
      most important predictors of long-term cardiac events in patients with coronary
      artery disease. Heart rate variability and QT dynamicity have been used as
      independent predictors for sudden death in coronary artery disease. Heart rate
      variability and QT dynamicity, however, have never been investigated in
      multivessel coronary artery disease. The aim of this study was to identify
      autonomic nervous system activity and ventricular vulnerability in multivessel
      coronary artery disease. METHODS: We examined 204 patients who underwent coronary
      angiography. According to the number of the three major coronary vessels with
      significant stenosis (>70%), we divided the patients into three groups: normal
      coronary arteries (n=61), single-vessel coronary artery disease (n=53) and the
      multivessel coronary artery disease (n=90). Twenty-four-hour ambulatory
      electrocardiographic recording was performed by a three-channel recorder. Heart
      rate variability and QT dynamicity parameters were obtained by ELA TEC software.
      RESULTS: Baseline characteristics were similar in multivessel coronary artery
      disease, single-vessel coronary artery disease and controls. SDNN (90+/-35, 117+/
      52, 134+/-53, respectively; P<0.001) and HFnu (9.6+/-8.2, 8.9+/-3.7, 12.2+/-7.4,
      respectively; P=0.011) were significantly lower, whereas LFnu (27.2+/-11.3,
      26.1+/-8.4, 22.0+/-13.4, respectively; P=0.014) and LF/HF ratio (4.4+/-3.2, 3.3+/
      1.4, 2.1+/-1.6, respectively; P<0.001) were significantly higher in multivessel
      coronary artery disease. QTend/RR and QTapex/RR slopes were more significantly
      increased in multivessel coronary artery disease than in single-vessel coronary
      artery disease and control participants [QTend/RR: 0.15 (0.04-0.66), 0.12 (0.02
      0.33), 0.12 (0.01-0.22), respectively; P=0.002; QTapex/RR: 0.16 (0.06-0.30), 0.12
      (0.02-0.29), 0.11 (0.01-0.19), respectively; P<0.001]. CONCLUSIONS: Heart rate
      variability and QT dynamicity are impaired in patients with multivessel coronary
      artery disease. Our results may indicate that heart rate variability and QT
      dynamicity parameters can be useful noninvasive methods that may detect autonomic
      nervous system activity and ventricular vulnerability in multivessel coronary
      artery disease.

PMID- 17496487
TI  - Metabolic syndrome and risk of acute coronary syndromes in patients younger than
      45 years of age.
AB  - OBJECTIVE: There is a paucity of data with regard to the association of the
      metabolic syndrome with cardiovascular risk in young adults. We investigated the
      association of the metabolic syndrome with acute coronary syndrome in adults aged
      45 years or younger. PATIENTS AND METHODS: A total of 136 consecutive patients
      (128 men and eight women; mean age, 41.2+/-3.7 years) presenting with a first
      ever acute coronary syndrome, and 136 age-matched and sex-matched controls were
      evaluated. The diagnosis of the metabolic syndrome was established according to
      the Adult Treatment Panel III criteria. RESULTS: The prevalence of the metabolic
      syndrome was significantly higher in the patients' group compared with the
      control group (40.4 versus 23.5%; P=0.003). Multivariate logistic regression
      analysis showed that smoking, positive family history of premature coronary
      artery disease, and the metabolic syndrome were associated with odds ratios 4.46
      (95% confidence interval, 2.30-8.66; P<0.001), 3.11 (95% confidence interval,
      1.71-5.66; P<0.001), and 1.97 (95% confidence interval, 1.08-3.56; P=0.02) higher
      odds, respectively, of having an acute coronary syndrome, after taking into
      account the matching for age and sex and controlling for potential confounders.
      Moreover, a 10-mg/dl increase in total cholesterol was associated with 1.06
      higher odds of having an acute coronary syndrome. Analysis of interaction showed
      that smoking and a positive family history of premature coronary artery disease
      in young individuals with metabolic syndrome had an incremental effect on the
      odds of suffering an acute coronary syndrome (odds ratio, 7.12; 95% confidence
      interval, 2.42-20.96; P<0.001). CONCLUSION: The metabolic syndrome is highly
      associated with acute coronary syndrome in patients younger than 45 years of age,
      indicating the need for early and intensive preventive measures.

PMID- 17496488
TI  - Brain natriuretic peptide concentration in pericardial fluid is independently
      associated with atrial fibrillation after off-pump coronary artery bypass
      surgery.
AB  - OBJECTIVES: Postoperative atrial fibrillation is associated with the increased
      incidence of morbidities and mortality. Predisposing determinants of atrial
      fibrillation development after off-pump coronary artery bypass grafting remain
      unclear. We hypothesized that pericardial fluid natriuretic peptide
      concentrations have a predictive value for developing postoperative atrial
      fibrillation in patients who have undergone off-pump coronary artery bypass
      grafting. METHODS: We prospectively measured atrial natriuretic peptide and brain
      natriuretic peptide concentrations in plasma and pericardial fluid in 42
      consecutive patients undergoing off-pump coronary artery bypass grafting, then
      continuously observed the occurrence of atrial fibrillation following off-pump
      coronary artery bypass grafting until the time of discharge. RESULTS:
      Postoperative atrial fibrillation was documented in nine patients (21%, atrial
      fibrillation group), and not in 33 patients (no atrial fibrillation group).
      Between the groups, there was neither significant difference in plasma atrial
      natriuretic peptide concentrations nor in pericardial atrial natriuretic peptide
      concentrations. Plasma brain natriuretic peptide concentrations were comparable
      in both groups [56.2 (interquartile range 42.7-102.8) vs. 35.2 pg/ml (13.8-75.0),
      P=0.07]. Pericardial fluid brain natriuretic peptide concentrations were
      significantly higher in the atrial fibrillation group than in the no atrial
      fibrillation group [188.0 (124.8-411.0) vs. 39.3 pg/ml (10.0-88.4), P=0.0001]. In
      a multivariable logistic regression model, pericardial brain natriuretic peptide
      concentration was significantly associated with a higher risk of postoperative
      atrial fibrillation (odds ratio=3.0 every 50 pg/ml increase; 95% confidence
      interval, 1.1-8.6; P=0.04). CONCLUSION: Our results suggested that pericardial
      fluid brain natriuretic peptide concentration is independently associated with
      the development of atrial fibrillation after off-pump coronary artery bypass
      grafting.

PMID- 17496489
TI  - Trimetazidine to reverse ischemia in patients with class I or II angina: a
      randomized, double-blind, placebo-controlled dobutamine-atropine stress
      echocardiography study.
AB  - AIMS: We sought to evaluate the effects of trimetazidine on ischemia induced by
      dobutamine-atropine stress echocardiography in patients with class I or class II
      angina. METHODS: In a randomized, double-blind, placebo-controlled study, 66
      patients with proved coronary disease were subjected to dobutamine-atropine
      stress echocardiography. Ischemia was proved in 56 patients who were included in
      the study and who had been on standard maintenance medications (propranolol,
      aspirin and statin). They were randomized to placebo or trimetazidine, 20 mg
      three times daily for a 12-week period, when dobutamine-atropine stress
      echocardiography was repeated. RESULTS: Fifty-two patients (56.53+/-8.9 years
      old) completed the study. No differences were seen between groups at entry.
      Thirty patients had class I and 26 class II angina. At the end of the study, 42
      had class I and 14 class II angina (P=0.01), owing to patients being in the
      trimetazidine arm. We did not observe any differences between groups either for
      onset time of ventricular ischemic dysfunction, or for wall-motion score index.
      Comparing variation at peak using the delta wall-motion score index, we observed
      no differences, but only a trend toward reduction favoring trimetazidine
      (P=0.09). CONCLUSION: We did not detect a significant anti-ischemic effect of
      trimetazidine in patients with mild angina, but there was a clear improvement in
      angina class.

PMID- 17496490
TI  - Diagnostic work-up of unselected patients with suspected coronary artery disease:
      complementary role of multidetector computed tomography, symptoms and
      electrocardiogram stress test.
AB  - AIM: We evaluated the accuracy of multidetector computed tomography in detecting
      coronary artery disease and how it could change the indication to coronary
      angiography in patients with suspected cardiac chest pain. METHODS AND RESULTS:
      We enrolled 142 consecutive patients who had already performed an exercise
      electrocardiogram test referred to our hospital and scheduled for coronary
      angiography for chest pain. According to the characteristics of chest pain and
      the results of exercise electrocardiogram, patients were divided into four
      groups: atypical chest pain and negative exercise electrocardiogram (group 1);
      typical chest pain and negative exercise electrocardiogram (group 2); atypical
      chest pain and positive exercise electrocardiogram (group 3); and typical chest
      pain with positive exercise electrocardiogram (group 4). We evaluated the
      accuracy of multidetector computed tomography and whether it could reduce the
      number of unnecessary coronary angiography in the study groups. Of 1801 segments
      larger than 1.5 mm, 1696 (94%) were assessable. In a segment based-model,
      sensitivity, specificity, negative predictive value, positive predictive value
      and accuracy were 81% (95% confidence interval 75-89%), 94% (95% confidence
      interval 90-98%), 96% (95% confidence interval 93-98%), 75% (95% confidence
      interval 69-82%) and 91% (95% confidence interval 89-93%), respectively. In a
      patient-based model, sensitivity, specificity, negative predictive value,
      positive predictive value and accuracy were 95% (95% confidence interval 91-99%),
      78% (95% confidence interval 67-89%), 88% (95% confidence interval 79-97%), 89%
      (95% confidence interval 83-95%) and 89% (95% confidence interval 84-94%).
      Unnecessary coronary angiography may be avoided by multidetector computed
      tomography results particularly in group 2 (16%) and group 3 (24%), whereas in
      groups 1 and 4 the role of multidetector computed tomography in facilitating the
      correct indication to coronary angiography was less relevant. CONCLUSIONS:
      Multidetector computed tomography is a particularly helpful technique in patients
      with discordance between the clinical features of chest pain and stress-test
      results. This technique may be introduced in the diagnostic work-up of patients
      with suspected coronary artery disease and may potentially reduce the number of
      unnecessary coronary angiography.

PMID- 17496491
TI  - Determinants of amount of contrast utilized in patients undergoing percutaneous
      coronary procedures.
AB  - OBJECTIVE: To determine predictors of contrast amount during coronary angiography
      and percutaneous coronary intervention. BACKGROUND: Contrast-induced nephropathy
      is a leading cause of hospital-acquired acute renal insufficiency. During
      percutaneous coronary procedures, contrast amount is a major risk factor
      incriminated in development of contrast-induced nephropathy. METHODS: Demographic
      and procedural details were obtained for consecutive patients undergoing
      percutaneous coronary procedures between January 2002 and October 2005 (N=962,
      mean+/-standard error of contrast amount: 216.6+/-3.0 ml) at a tertiary care
      hospital. RESULTS: A significant difference (P value <0.05) in unadjusted mean
      contrast volume was observed between subgroups of percutaneous coronary
      intervention vs. coronary angiography, patients with a history of coronary artery
      bypass grafting, patients undergoing additional procedures and multivessel and
      multisite percutaneous coronary interventions. On General Linear Model analysis,
      independent predictors (beta coefficient, 95% confidence interval, P value) of
      increased contrast amount during percutaneous coronary procedures were history of
      coronary artery bypass grafting (44.4, 30.6-58.2, <0.001), type of coronary
      procedure (85.2, 73.4-97.0, <0.001 for percutaneous coronary intervention vs.
      coronary angiography), number of interventions and number of additional
      procedures performed. Among additional procedures, rotablation, intravascular
      ultrasound and Angiojet were associated with increased contrast use. No
      significant independent effect on the contrast amount was observed with
      percutaneous coronary intervention location (right coronary artery vs. left
      anterior descending artery vs. circumflex artery) site (ostial vs. proximal vs.
      mid vs. distal) of percutaneous coronary intervention or with interventions on
      chronic total occlusions on the contrast amount. CONCLUSION: Data from our study
      could guide the coronary angiographer in moderating the volume of contrast
      utilized as well as assist with the elective planning of complex therapeutic
      procedures.

PMID- 17496492
TI  - Reproducibility of transthoracic echocardiography in small animals using clinical
      equipment.
AB  - OBJECTIVE: Transthoracic echocardiography has been employed to assess left
      ventricular dimensions and function in small animals. The aim of this study was
      to identify the limits of transthoracic echocardiography in a commonly used
      Wistar rat model by assessing intraobserver variability, interobserver
      variability, and day-to-day variability of examinations implying registrations
      and measurements. METHODS: Twenty male adult Wistar rats (body weight 496+/-52 g)
      were examined under volatile isoflurane anesthesia (heart rate 302+/-26 bpm) by
      transthoracic echocardiography (Sonos 7500; Philips) with a 15 MHz-transducer.
      For calculation of intraobserver variability, examinations were repeated by the
      same examiner and for interobserver variability, examinations were performed
      independently by two investigators. For day-to-day variability, examinations were
      repeated 14 days later. Left ventricular diameters and areas were analyzed in
      parasternal short axis and in a modified parasternal long axis. Fractional
      shortening, area shortening, ejection fraction, stroke volume, and cardiac output
      were calculated. RESULTS: Left ventricular end-diastolic diameter was 8.9+/-0.6
      mm, fractional shortening 39.0+/-5.3%, area shortening 59.6+/-6.1%, ejection
      fraction 83.3+/-5.1%, stroke volume 0.24+/-0.06 ml, and cardiac output 72.9+/
      20.6 ml/min. Intraobserver variability of left ventricular end-diastolic
      diameter, fractional shortening, area shortening, and ejection fraction was less
      than 10%, increasing to 19% for stroke volume and cardiac output. Interobserver
      variability of left ventricular end-diastolic diameter, fractional shortening,
      area shortening, ejection fraction was less than 13%, increasing to 23% for
      stroke volume and 25% for cardiac output. Day-to-day variability of left
      ventricular end-diastolic diameter, area shortening, ejection fraction was less
      than 11% whereas for stroke volume it was 21% and for cardiac output it was 22%.
      F-ratio test comparing investigated variabilities did not reveal significant
      differences. CONCLUSIONS: M-mode and two-dimensional echocardiography in large
      rats by clinically common high-end ultrasound systems can be assessed reliably.
      Parameters of global left ventricular performance like stroke volume and cardiac
      output could not be assessed with similar reliability.

PMID- 17496493
TI  - Is there delayed restenosis in patients with coronary artery disease treated with
      sirolimus-eluting stent?
AB  - BACKGROUND: Although long-term follow-up after sirolimus-eluting stent
      implantation shows a sustained clinical benefit in several randomized and
      registered trials, little is known about the pattern of neointimal growth beyond
      the first 6 to 9 months. In this study, we therefore evaluated the possible
      delayed restenosis in patients with coronary artery disease treated with
      sirolimus-eluting stent. METHODS: A total of consecutive 333 patients with 453
      lesions were enrolled in this study (among 782 consecutive patients with 1023
      lesions). Lesions were subjected to follow-up by quantitative coronary
      angiography, and patients were divided into two groups according to the time of
      follow-up by quantitative coronary angiography: early group (< or =270 days,
      n=270 with 369 lesions) and late group (>270 days, n=63 with 84 lesions). Binary
      restenosis was defined as stenosis of more than 50% of the lumen diameter in the
      target lesion. RESULTS: Baseline clinical, demographic or angiographic
      characteristics were well balanced between the two groups. The in-stent
      restenosis rate was not significant between the early group and the late group
      (3.5 vs. 6.0%; P>0.05). The late loss and target lesion revascularization
      appeared higher in late group but there were no significant differences (0.15+/
      0.38 mm vs. 0.24+/-0.44 mm; and 4.9 vs. 9.5%, P>0.05, respectively). Similarly,
      overall thrombosis rate was also same in both groups. In-segment restenosis was,
      however, higher in late group compared with that in early group (7.9 vs. 16.7%,
      P=0.013). CONCLUSION: In this unrestricted population, the beneficial effects of
      sirolimus-eluting stent implantation extend out more than 1 year in real world
      practice, that has been confirmed by the results of the large randomized clinical
      trials. The late in-segment restenosis could, however, be found, suggesting that
      a prolonged clinical and angiographic surveillance in this subset of patients
      seems to be warranted.

PMID- 17496494
TI  - More aggressive pharmacological treatment may improve clinical outcome in
      patients with non-ST-elevation acute coronary syndromes treated conservatively.
AB  - INTRODUCTION: Increased adherence to guideline-recommended therapies, especially
      early invasive strategy introduction may improve clinical outcome in patients
      with non-ST-elevation acute coronary syndromes. The aim of this study was to
      assess the impact of more aggressive pharmacological treatment and application of
      current guidelines in everyday clinical practice in hospitals without on-site
      invasive facility, with a special focus on its influence on in-hospital mortality
      in non-ST-elevation acute coronary syndromes patients. METHODS: We identified 807
      non-ST-elevation acute coronary syndromes patients treated conservatively in the
      29 hospitals participating in the Malopolska Registry of Acute Coronary Syndromes
      from February to March 2005 and from December 2005 to January 2006. For all
      patients, pharmacotherapy index based on the use of pharmacological treatment
      regimen during hospital stay was assessed. Each patient received 1 point for each
      of the following guideline-recommended drugs used: aspirin, clopidogrel,
      glycoprotein IIb/IIIa inhibitor, low-molecular-weight heparin, beta-blocker,
      angiotensin converting enzyme inhibitor/angiotensin II receptor blocker, statin -
      range of points from 0 to 7. RESULTS: The in-hospital mortality decreased with
      increase of pharmacotherapy index (0 points - 80.0%, 1 point - 36.4%, 2 points -
      17.4%, 3 points - 7.6%, 4 points - 5.6%, 5 points - 1.7%, 6 points - 0.0%;
      P<0.0001, total mortality-5.3%). Independent predictors of in-hospital death were
      cardiogenic shock, thrombolysis in myocardial infarction (TIMI) risk score, renal
      insufficiency and pharmacotherapy index. CONCLUSIONS: Our findings support the
      need for more aggressive pharmacological treatment of patients with non-ST
      elevation acute coronary syndromes remaining in community hospitals for
      conservative treatment. Broader implementation of current guidelines and more
      frequent invasive treatment could improve the outcomes of non-ST-elevation acute
      coronary syndromes patients.

PMID- 17496495
TI  - Small vessel stenting with cobalt-chromium stents (Arthos Pico) in a real world
      setting.
AB  - BACKGROUND: In current clinical practice, 35-67% of significant coronary artery
      lesions are located in small (<3.0 mm) vessels, a setting with poor short- and
      long-term results after percutaneous coronary interventions. OBJECTIVES: The aim
      of the present Arthos Pico Austria Multicenter Registry is to demonstrate the
      safety and efficacy of the Arthos Pico (cobalt-chromium alloy) stent implantation
      in small coronary arteries in a real world setting. METHODS: Two hundred and
      three patients (mean age, 67+/-12 years; 63% male) were included in the Registry;
      199 patients (98%) were controlled clinically (including noninvasive stress
      tests) 6 and 12 months after stent implantation. Clinically driven angiographic
      controls were performed in 37 patients (18.2%) at mean 6 months after stenting.
      The primary endpoint of the study was the 6-month rate of major adverse cardiac
      events (as target vessel revascularization, all cause death, and acute myocardial
      infarction), the secondary endpoints were the intervention complications, and the
      occurrence of acute and subacute stent thrombosis. RESULTS: The procedural
      success was 99%. The rates of acute and subacute stent thrombosis were 0.5 and
      1.5%, respectively. During the 6-month clinical follow-up, primary endpoint
      events (major adverse cardiac events) were recorded in 13% of the clinically
      controlled patients: four patients (2%) with acute myocardial infarction; 12
      patients (6%) with target vessel revascularization; and 10 patients died (5%),
      resulting in an event-free survival rate of 87%. Between the 6- and 12-month
      follow-up, additional target vessel revascularization was performed in three
      patients, acute myocardial infarction and death occurred in one patient each,
      respectively. Thus, the 12-month major adverse cardiac event-free survival rate
      was 85%. Patients who died had older age (76+/-7 years) and a high proportion of
      type C lesions (50%) at the initial angiography. Multivariate analysis revealed
      older age (P=0.026) and type C lesions (P=0.016) as significant predictors for
      all causes of death. CONCLUSION: In conclusion, stenting of small arteries with
      Arthos Pico is safe and effective in the prevention of major adverse cardiac
      events during 6- and 12-month follow-up.

PMID- 17496496
TI  - QRS score improves diagnostic ability of treadmill exercise testing in women.
AB  - OBJECTIVE: The accuracy of treadmill exercise testing to detect coronary artery
      disease is limited in women. This study was undertaken to evaluate whether QRS
      score can improve the accuracy of treadmill exercise testing in women. METHODS:
      The study population consisted of 114 women with angina-like symptoms, who
      underwent both treadmill exercise testing and coronary angiography. The impact of
      QRS score on the standard ST-segment based diagnostic ability of treadmill
      exercise testing to detect coronary artery disease was studied. RESULTS:
      Incorporation of QRS score in standard ST-segment diagnostic criteria
      significantly enhanced sensitivity (from 59 to 80%), specificity (from 40 to 94%)
      and diagnostic accuracy (from 50 to 87%) of treadmill exercise testing. The QRS
      score was shown to reduce significantly the false-positive results from 60 to 6%.
      Furthermore, QRS score accuracy was correlated with the extent of coronary artery
      disease. The diagnostic ability of QRS score was greater both among patients with
      normal and impaired systolic function of the left ventricle. CONCLUSIONS: QRS
      score can improve the limited diagnostic accuracy of treadmill exercise testing
      in women, by predominantly decreasing the high prevalence of false-positive
      results.

PMID- 17496497
TI  - Remnant-like lipoprotein particle level and insulin resistance are associated
      with in-stent restenosis in patients with stable angina.
AB  - BACKGROUND: The aim of this study was to evaluate the independent effect of serum
      remnant-like lipoprotein particle level and insulin resistance on in-stent
      restenosis in nondiabetic patients with stable angina. METHODS: The study
      included 64 nondiabetic patients with stable angina who underwent successful
      coronary stenting. At the time of stenting, we evaluated the patients' lipid
      profiles including remnant-like lipoprotein particles cholesterol, plasma glucose
      and insulin levels, and insulin resistance by the homeostasis model assessment.
      RESULTS: There was no significant difference in total cholesterol, low-density
      lipoprotein cholesterol, and high-density lipoprotein cholesterol levels between
      two patient groups with (n=15) and without (n=49) in-stent restenosis. Plasma
      remnant-like lipoprotein particles cholesterol level was significantly higher in
      patients with restenosis than in patients without restenosis (8.2+/-7.0 mg/dl vs.
      4.5+/-2.6 mg/dl, P=0.006). Although plasma glucose level was similar between the
      two groups, insulin level and homeostasis model assessment were significantly
      higher in patients with restenosis, compared with those without restenosis
      (11.2+/-12.4 vs. 7.1+/-2.8, P=0.039; and 2.6+/-2.9 vs. 1.7+/-0.7, P=0.040,
      respectively). In multivariate logistic regression analysis, plasma remnant-like
      lipoprotein particles cholesterol level (>4.8 mg/dl; the 75th percentile of the
      distribution of remnant-like lipoprotein particles cholesterol level) was the
      independent predictor of in-stent restenosis (odds ratio: 8.15; confidence
      interval: 1.02-65.16; P=0.048). CONCLUSIONS: Our findings suggest that high serum
      remnant-like lipoprotein particles cholesterol level, and not insulin resistance
      may be an independent risk factor on in-stent restenosis in nondiabetic patients
      with stable angina.

PMID- 17496498
TI  - Bibliography current world literature.

PMID- 17496499
TI  - New age literacy: expectations for deans.
AB  - Many new nursing leaders assuming deanships, assistant or interim deanships have
      limited education, experience, or background to prepare them for the job. To
      assist new deans and those aspiring to be deans, the authors of this department,
      2 deans, offer survival tips based on their personal experiences and insights.
      They address common issues, challenges, and opportunities that face academic
      executive teams, such as negotiating an executive contract, obtaining faculty
      lines, building effective work teams, managing difficult employees, and creating
      nimble organizational structure to respond to changing consumer, healthcare
      delivery, and community needs. The authors welcome counterpoint discussions with
      readers.

PMID- 17496500
TI  - Strategies for creating social presence online.

PMID- 17496501
TI  - Nurses' perceptions of working with students in the clinical setting.

PMID- 17496502
TI  - Setting the passing standard for the National Council Licensure Examination for
      Registered Nurses.
AB  - The Board of Directors of the National Council of State Boards of Nursing
      evaluates the NCLEX-RN examination passing standard every 3 years. In December
      2006, the Board decided that the NCLEX-RN passing standard should be increased
      from -0.2800 to -0.2100 logits. This article provides information regarding
      standard-setting methodologies, empirical data used by the Board of Directors in
      determining the passing standard, and implications of the new passing standard
      for faculty.

PMID- 17496503
TI  - Decreasing transactional distance in a Web-based course.
AB  - The Horizon Wimba online Web-conferencing voice system was used to facilitate
      dialogue and decrease transactional distance in a Web-based course. Small-group
      (< or =6)discussion sessions were held and addressed topics pertinent to clinical
      practice. Students were asked to evaluate the synchronous voice discussion groups
      via a Flashlight survey at the end of the semester. Anecdotal and survey
      responses indicated that discussion groups increased dialogue between faculty and
      students.

PMID- 17496504
TI  - Engaging students through the use of classroom response systems.
AB  - Nursing faculty strive to stimulate learning and actively engage students in the
      classroom. Developing new approaches to student engagement in large classrooms
      can be a challenging task. The use of a classroom response system encourages
      students to actively participate while learning essential nursing knowledge in a
      way that adheres to principles of adult learning.

PMID- 17496505
TI  - Individualized student advisement for preparation for the national council
      licensure examination for registered nurses: a community college experience.
AB  - The success of faculty is, in part, measured by the success of their students.
      One measurement of student success is passing the National Council Licensure
      Examination for Registered Nurses. However, some students require assistance
      beyond routine class work; they require a personalized plan for studying based on
      individualized areas of weakness. The author reviews the process of implementing
      a program of individualized student advisement. Included are samples of forms
      that have been developed to assist in this process.

PMID- 17496506
TI  - Online tutors as a solution to the shortage of nurse practitioner educators.
AB  - The shortage of nursing faculty in Canada, particularly those qualified to teach
      students in nurse practitioner programs, has contributed to the use of adjunct
      teachers and online methodologies. The author discusses 1 nurse practitioner
      online program's use of nurse practitioners who work in full-time clinical roles
      as tutors. Learning through experience, the author shares how the online tutor
      role was developed to assist those who are considering using tutors as a program
      delivery strategy.

PMID- 17496507
TI  - Lessons learned from 12 years of teaching second-degree BSN students.
AB  - Second-degree BSN-accelerated nursing programs are no longer considered new or
      rare, with many schools of nursing having programs that have been in place for
      over a decade. Auburn University is one such school. The focus and motivation of
      these students make teaching them challenging and rewarding. The authors describe
      lessons learned including how to promote socialization of accelerated nursing
      degree students and use faculty resources efficiently.

PMID- 17496508
TI  - Preventing musculoskeletal disorders in nurses: a safe patient handling
      curriculum module for nursing schools.
AB  - Nursing educators who teach outmoded manual patient handling techniques
      contribute to the widespread problem of musculoskeletal disorders in student and
      practicing nurses. The authors discuss the development and implementation of a
      new safe patient handling curriculum module, which was pilot tested in 26 nursing
      programs. The module changes the focus of patient handling education from body
      mechanics to equipment-assisted safe patient lifting programs that have been
      shown to protect nurses from injury and improve care.

PMID- 17496509
TI  - Interdisciplinary clinical education: implementing a gerontological home visiting
      program.
AB  - The Interdisciplinary House Calls program was a collaborative effort between a
      Midwestern medical school and a university, designed to give students from
      various health-related disciplines the opportunity to experience
      interdisciplinary team work in a clinical setting. Medical, nursing,
      communication disorders, and health sciences students formed teams and completed
      4 home visits to assigned elderly patients over 18 months. Students learned the
      importance of collaboration and reported an appreciation of the contributions of
      each health-related discipline.

PMID- 17496511
TI  - A preliminary report--heparin counteracts indomethacin effect on ductus
      arteriosus in very low birthweight infants.
AB  - OBJECTIVE: We report a clinical observation showing that continuous exposure to
      heparin via a central venous catheter is associated with patent ductus arteriosus
      treatment failure with indomethacin in very low birthweight infants. STUDY
      SELECTION: A clinical observational case report in infants weighting <1501 g.
      DATA EXTRACTION: This study compares the rates of patent ductus arteriosus
      treatment failure during a) the index period from June 2, 2003, to August 22,
      2003, when all very low birthweight infants with a peripherally inserted central
      venous catheter received continuous infusion of heparinized parenteral nutrition;
      b) the baseline period of 1 yr before the index period; and c) the postindex
      period of 1 yr after the index period. DATA SYNTHESIS: The rate of patent ductus
      arteriosus treatment failure with indomethacin increased significantly during the
      index period compared with the baseline (odds ratio, 7.0; 95% confidence
      interval, 1.41-34.7; p = .017) and postindex periods (odds ratio, 33.8; 95%
      confidence interval, 4.72-243; p = .0005). The result was confirmed in logistic
      multivariable regression analysis. CONCLUSION: This observation, based on a case
      series and their controls, serves as a basis for a new hypothesis suggesting that
      continuous exposure to heparin through heparinized central venous infusion
      significantly increases patent ductus arteriosus treatment failure with
      indomethacin. This hypothesis needs to be tested in a randomized controlled
      trial.

PMID- 17496512
TI  - Critical pertussis may model organ failure in critical illness and injury.

PMID- 17496513
TI  - Organ donation after cardiac death: the subtle line between patient and donor
      care.

PMID- 17496514
TI  - Parental presence during bedside pediatric intensive care unit rounds.

PMID- 17496515
TI  - Can policy spoil compassion?

PMID- 17496516
TI  - Community-acquired methicillin-resistant Staphylococcus aureus: a new scourge so
      virulent even extracorporeal membrane oxygenation may not help?

PMID- 17496517
TI  - Rapid response systems: is yet another before-and-after trial needed?

PMID- 17496518
TI  - Transhepatic approach as an alternative long-term central venous access in
      critically ill children with complex congenital heart disease: a new angle to an
      old problem?

PMID- 17496519
TI  - Calcium: a double-edged sword.

PMID- 17496520
TI  - Patency of the ductus arteriosus in the newborn--now you want it, now you don't.

PMID- 17496521
TI  - Computerized physician order entry: friend or foe?

PMID- 17496522
TI  - Testing the waters.

PMID- 17496524
TI  - Can somatostatin derivatives really be suggested in the treatment of chylothorax?

PMID- 17496526
TI  - Reducing the risks of cardiovascular disease in liver allograft recipients.
AB  - Liver allograft recipients are at increased risk of death from cerebrovascular
      and cardiovascular disease. We propose the following strategy of risk-reduction,
      based on currently available literature. Lifestyle: standard advice should be
      given (avoidance of smoking, excess alcohol and obesity, adequate exercise,
      reduction of excess sodium intake). Hypertension: target blood pressure should be
      140/90 mmHg or lower, but for those with diabetes or renal disease, 130/80 mmHg
      or lower. For patients without proteinuria, antihypertensive therapy should be
      initiated with a calcium channel blocker and for those with proteinuria, an
      angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker.
      If monotherapy fails to achieve adequate response, calcium channel blockers and
      ACE-inhibitors or angiotensin II receptor blockers should be combined. If
      hypertension remains uncontrolled, an alpha-blocker may be added. Consideration
      should be given to changing immunosuppression and avoiding use of calcineurin
      inhibitors. Diabetes: recipients should be regularly screened for diabetes. For
      patients with new-onset diabetes after transplant, stepwise therapy should be
      guided by HbA1c concentrations, as with type II diabetes mellitus.
      Hyperlipidemia: annual screening of lipid profile should be undertaken, with
      treatment thresholds and targets based on those advocated for the high risk
      general population. Dietary intervention is appropriate for all patients. A
      statin should be considered as the first line treatment to achieve specified
      targets. In patients receiving a calcineurin inhibitor, Pravastatin should be
      commenced at a dose of 10 mg/day. In patients receiving other forms of
      immunosuppression, pravastatin may be commenced at a dose of 20 mg/day. Liver
      tests should be monitored and patients warned to report myalgia. If monotherapy
      is inadequate, ezetimibe or a fibrate may be added. Consideration may be given to
      change in immunosuppression if combination lipid-lowering therapy proves
      inadequate.

PMID- 17496527
TI  - The new deceased donor pancreas allocation schema: do the recommendations go far
      enough?

PMID- 17496529
TI  - The rationale for the new deceased donor pancreas allocation schema.
AB  - BACKGROUND: To ensure the continued success of whole organ pancreas and islet
      transplantation, deceased donor pancreas allocation policy must continue to
      evolve. METHODS: To assess the existing system, the Organ Procurement and
      Transplantation Network (OPTN)/United Network for Organ Sharing Kidney and
      Pancreas Transplant Committee retrospectively analyzed the disposition and
      outcomes of deceased donor pancreata in the United States between January 1, 2000
      and December 31, 2003. RESULTS: During the time period studied, consent was
      obtained but the pancreas was not recovered in 48% (11,820) of organ donors. The
      most common reasons given for nonrecovery were poor quality of the pancreas and
      difficulty in placement. Of whole organ pancreata that were transplanted, 90%
      were from donors with a body mass index (BMI) <or=30 kg/m and age <or=50 years.
      Pancreata from older and more obese donors were used more often for islet
      transplantation or research. For simultaneous pancreas-kidney transplants, the 1-
      and 3-year pancreas graft survival was lower when the donor was age >50 years
      (P=0.04), and there were trends toward lower graft survival with donor BMI >30
      (P=0.06) and increasing cold-ischemia time. CONCLUSIONS: Based on these data, the
      OPTN adopted a new allocation algorithm in which pancreata from donors >30 kg/m
      or >50 years of age are, unless accepted for a local whole organ pancreas
      transplant candidate, preferentially allocated for islet transplantation. These
      data also suggest that many good quality pancreata are not procured, emphasizing
      the need for improved communication and cooperation between organ procurement
      organizations and pancreas and islet transplant programs.

PMID- 17496528
TI  - Implementation of a Protocol for ABO-incompatible kidney transplantation--a three
      center experience with 60 consecutive transplantations.
AB  - BACKGROUND: A new protocol for ABO-incompatible kidney transplantation has
      recently been introduced. We report here on the joint experience of the
      implementation in Stockholm and Uppsala, Sweden and Freiburg, Germany. METHODS:
      The new protocol utilizes antigen-specific immunoadsorption to remove existing
      ABO-antibodies, rituximab, and intravenous immunoglobulin to prevent the rebound
      of antibodies, and conventional tacrolimus, mycophenolate-mofetil, and
      prednisolone immunosuppression. Sixty consecutive ABO-incompatible kidney
      transplantations were included in the study. The outcome is compared with the
      results of 274 ABO-compatible live donor transplantations performed during the
      same period. RESULTS: Two of the ABO-incompatible grafts have been lost (non
      compliance and death with functioning graft). All the remaining 58 grafts had
      good renal function at a follow-up of up to 61 months. We did not observe any
      late rebound of antibodies and there were no humoral rejections. Graft survival
      was 97% for the ABO-incompatible compared with 95% for the ABO-compatible.
      Patient survival was 98% in both groups. There was a significant variation in
      preoperative A/B-antibody titer between the centers, with a median 1:8 in
      Uppsala, median 1:32 in Stockholm and median 1:128 in Freiburg. More preoperative
      antibody adsorptions were therefore needed in Freiburg than in Stockholm and
      Uppsala. CONCLUSIONS: The new protocol was easily implemented and there were no
      graft losses that could be related to ABO-incompatibility. A significant inter
      institutional variation in the measurement of anti-AB-antibodies was found,
      having a substantial impact on the number of immunoadsorptions and consequently
      on the total cost for the procedure. A standardized fluorescence-activated cell
      sorting technique for antibody quantification is much needed.

PMID- 17496530
TI  - De novo sirolimus-based immunosuppression after liver transplantation for
      hepatocellular carcinoma: long-term outcomes and side effects.
AB  - BACKGROUND: We report long-term outcomes and side effects after transplantation
      for hepatocellular carcinoma (HCC) using de novo, sirolimus-based
      immunosuppression (IS). METHODS: A total of 70 patients with HCC (mean age:
      54.4+/-7 years, female/male: 12/58) were transplanted and included in the study.
      Immunosuppression included de novo sirolimus, low-dose calcineurin inhibitor for
      6 to 12 months, with short-course (3 months) or no steroids. RESULTS: After 49
      months-median follow-up, eight patients have experienced an HCC recurrence, 2 of
      34 when Milan criteria were respected (6%) and 6 of 36 when beyond Milan criteria
      (17%). One- and 4-year tumor-free survivals were 85 and 73%, when Milan criteria
      were respected and 82% and 75% when they were not, respectively. (P=0.9). After
      recurrence, mean survival was 23+/-28 months. Half (35 of 70) of the patients
      experienced a rejection. Incisional hernia (24 of 70, 34%), wound infection (12
      of 70, 17%), anemia (39 of 70, 56%), leucopenia (39 of 70, 56%), high
      triglyceride (43 of 70, 61%), and cholesterol (28 of 70, 40%) levels and mouth
      ulcers (20 of 70, 29%) were among the most frequent complications. No hepatic
      artery thrombosis was observed. CONCLUSIONS: These data suggest that de novo
      sirolimus-based immunosuppression is associated with satisfactory outcomes after
      transplantation, even in selected patients beyond Milan criteria. The protocol
      has proven safe, with an acceptable side-effect profile. This study supports the
      conduct of larger randomized trials investigating sirolimus after transplantation
      for HCC.

PMID- 17496531
TI  - Renal transplantation in the United Kingdom for patients from ethnic minorities.
AB  - BACKGROUND: To investigate any differences in access to transplant and post
      transplant outcomes for ethnic minority patients in the United Kingdom, national
      data on ethnicity of patients on the waiting list, those receiving a transplant,
      and deceased donors were analyzed. METHODS: Adult patients and donors were
      included. Ethnic origin was classified as white, Asian, black, or "other."
      National data were analyzed, and 2001 U.K. National census data were used for
      comparative purposes. Median waiting times to transplant were obtained from
      Kaplan-Meier estimates for patients registered 1998-2000. Transplant survival was
      estimated for patients transplanted from 1998 to 2003. RESULTS: A total of 92% of
      the U.K. population was white, compared with 77% of waiting list patients, 88% of
      transplant recipients, and 97% of deceased donors. Median waiting time to
      transplantation for white patients was 719 days (95% confidence interval 680-758)
      compared with 1368 (1131-1605) days for Asian patients and 1419 (1165-1673) days
      for black patients. The degree of human leukocyte antigen matching achieved was
      inferior for Asian and black patients. There is some evidence of inferior 3-year
      transplant survival for black patients compared with white and Asian patients
      (P=0.03). CONCLUSIONS: There are imbalances in the ethnic make up of the waiting
      list, the donor pool, and renal transplant recipients. There are significant
      differences in both post-transplant outcomes and time to transplantation between
      patients of different ethnic origin. Waiting times are influenced by allocation
      schemes, and the 2006 U.K. National Kidney Allocation Scheme is designed to
      achieve greater equity of access to transplant for all patients, regardless of
      geography, blood group, or ethnicity.

PMID- 17496532
TI  - Effect of brain-dead donor resuscitation on delayed graft function: results of a
      monocentric analysis.
AB  - BACKGROUND: We have previously shown that a delayed graft function (DGF) longer
      than 6 days was a crucial threshold for long-term graft outcome. The aim of this
      study was to analyze the correlation of DGF >or=6 days with brain-dead donor
      variables, including those related to resuscitation, in a population of 262
      consecutive brain-dead donors from 1990 to 2003. METHODS: We used a marginal
      logistic model in which DGF was considered as a binary variable with a cutoff of
      6 days. RESULTS: Monovariate analysis of donor parameters showed that male, age
      above 35 years, primary history of hypertension, hydroxyethyl starch (HES) fluid
      greater than 1500 mL or epinephrine infusion during resuscitation were risk
      factors for prolonged DGF. The multivariate logistic regression model showed that
      epinephrine use during donor resuscitation (P<0.001, odds ratio [OR]=4.35), cold
      ischemia time (CIT) >or=16 hr (P=0.01, OR=2.16), and recipient age >55 years
      (P=0.003, OR=2.75), were associated with a risk of prolonged DGF. A long stay
      (>40 hr) in intensive care and a large volume of colloids (>1250 mL, except HES)
      correlated with a lower risk of DGF. CONCLUSION: Our study shows an impact for
      only a limited number of brain dead donor resuscitation parameters on DGF
      duration. We also show that CIT has a much lower threshold (<16 hr) for DGF risk
      than previously described. Importantly, we show that recipient age is clearly a
      major independent risk factor for prolonged DGF, whereas donor age seems to act
      mostly as a dependent risk factor.

PMID- 17496533
TI  - The prevention of recrudescent coccidioidomycosis after solid organ
      transplantation.
AB  - BACKGROUND: Coccidioidomycosis is an endemic fungal infection of the southwestern
      United States that causes considerable morbidity and mortality in transplant
      recipients, often as the result of reactivated infection. METHODS: A
      retrospective review of the medical records of 47 patients with prior
      coccidioidomycosis who underwent solid organ transplantation (18 liver, 24
      kidney, 3 pancreas, and 2 combined organ) at our tertiary care academic medical
      center. RESULTS: Of 47 transplant recipients with a history of
      coccidioidomycosis, 44 had quiescent infection at transplantation. Of the three
      with active coccidioidomycosis at transplantation, two were taking azole
      prophylaxis and had no further coccidioidal infection after transplantation. One
      of the three had positive serologic findings identified only on the day of
      transplantation, and prophylaxis was initiated a few hours after surgery along
      with immunosuppression; nevertheless, the treatment course was complicated by
      disseminated coccidioidomycosis. Seven patients did not initiate or self
      discontinued prophylaxis; one patient who discontinued prophylaxis experienced
      recurrent pulmonary infection. CONCLUSIONS: For patients undergoing
      transplantation in an area endemic for coccidioidomycosis, we recommend routine
      evaluation for evidence of prior infection and initiation of azole prophylaxis.
      For our patients with quiescent infection, azoles suppressed any recrudescent
      coccidioidomycosis after transplantation. The selection of patients who would
      benefit from prophylaxis and the optimal dose and duration of such prophylaxis
      should be studied further.

PMID- 17496534
TI  - A single-center experience of renal transplantation in elderly patients: a paired
      kidney analysis.
AB  - BACKGROUND: Chronic renal failure is a disease of the elderly. The elderly are
      the fastest growing population among dialysis patients and also on waiting lists
      for kidney transplantation. The objective for this study was to analyze the
      results of the renal transplantation in recipients elder than 60 years. To
      minimize the donor variability and bias, a paired kidney analysis was used.
      METHODS: The older renal transplantation (ORT) group included 44 patients (30
      men, 14 women) aged 60 to 72 (mean 64+/-3) years. Their pairs created a younger
      renal transplantation (YRT) group consisting of 44 patients (30 men, 14 women)
      aged 14 to 59 (mean 40+/-12) years. RESULTS: Graft function estimated 1 year
      after transplantation applying abbreviated Modification of Diet in Renal Disease
      formula was significantly better in ORT (46.8+/-10.2 ml/min) versus YRT (43.7+/
      16.8 ml/min). Studied groups (ORT vs. YRT) did not differ significantly with
      respect to 1-year patient survival (93.2% vs. 95.5%), 1-year graft survival
      (88.6% vs. 86.3%), 1-year death-censored graft survival (93% vs. 90.1%), and the
      incidences of delayed graft function and acute rejection. The most common
      complications noticed after ORT were cardiovascular complications, surgical
      complications, and infections. CONCLUSIONS: Our single-center results confirm
      that renal transplantation is a good option of renal replacement therapy in
      patients older than 60 years. Thorough recipient selection and preparation as
      well as customized immunosuppressive protocols are particularly important in that
      group of renal transplant recipients.

PMID- 17496535
TI  - Outcome of kidney transplantation from nonheart-beating versus heart-beating
      cadaveric donors.
AB  - BACKGROUND: This study aimed to assess outcomes of kidney transplants from
      nonheart-beating (NHB) compared with heart-beating (HB) cadaveric donors with
      meta-analytical techniques. METHODS: A literature search was performed for
      studies comparing kidney transplants from NHB vs. HB cadaveric donors between
      1992 and 2005. The following outcomes were evaluated: warm and cold ischemia
      times, primary nonfunction, delayed graft function, length of hospital stay,
      acute graft rejection, patient and graft survival, and post-transplant serum
      creatinine. RESULTS: Eighteen comparative studies of 114,081 patients matched the
      selection criteria; 1,858 received kidney from NHB and 112,223 from HB donor.
      Warm ischemia time was significantly longer for the NHB group by 24 min
      (P<0.001). Cold ischemia time was similar for the two groups (P=0.97). The
      incidence of primary nonfunction and delayed graft function was 2.4 times
      (P<0.001) and 3.6 times (P<0.001) greater, respectively, in the NHB group. Length
      of hospital stay was longer for the NHB group by 4.6 days (P<0.001). The 6-month,
      2-year, and 5-year patient survival were similar between the two groups. The
      incidence of acute rejection was similar between the two groups whereas the
      initial graft survival advantage in favor of the HB group diminished gradually
      over the course of time. There was no statistically significant difference
      between the two groups for the recipient serum creatinine levels at 3 and 12
      months after transplantation. CONCLUSION: NHB donors carry the potential of
      expanding the cadaveric kidney pool. Although, transplants from NHB donors are
      associated with a greater incidence of early adverse events, long-term outcomes
      appear comparable with those of transplants from HB donors.

PMID- 17496536
TI  - A prospective assessment of cytomegalovirus immune evasion gene transcription
      profiles in transplant patients with cytomegalovirus infection.
AB  - BACKGROUND: The cytomegalovirus (CMV) immune evasion genes US3, US6, and US11 may
      disrupt the host immune response via downregulation of major histocompatibility
      complex molecules. Transplant recipients with CMV infection were prospectively
      assessed for immune evasion gene expression. METHODS: Seventy solid organ
      transplant patients with CMV infection who were given antiviral therapy were
      enrolled. Quantitative mRNA levels of US3, US6, and US11 were assessed using real
      time polymerase chain reaction assays from peripheral blood mononuclear cells at
      regular time-points after starting therapy. RESULTS: High immune evasion mRNA
      levels were detectable at start-of-therapy (median US3-4.5 log10 copies; US6- 3.7
      log10 copies, and US11-3.3 log10 copies/10 cells). With therapy, immune evasion
      mRNA levels declined exponentially. For example, median calculated US3 half-life
      was 1.59 days (range 0.74-12.5 days). By day7, US3 mRNA was detectable in 55.7%,
      US6 in 38.6%, and US11 in 41.4% of patients. Early phase kinetics correlated with
      outcomes. When adjusted for baseline DNA level, there was a trend to higher mRNA
      levels in patients who relapsed. Also, detectable mRNA at day 14 after start of
      therapy was associated with virologic relapse after initial treatment (P<or=0.001
      for US3, US6, and US11). For example, if US3 mRNA was still detectable at day 14,
      then risk of relapse was 84.2% vs. 29.4% if US3 mRNA not detectable at day 14
      (P<0.001). This correlation was independent of the DNA viral load. CONCLUSION:
      CMV immune evasion gene expression is detectable at high levels in patients with
      CMV infection and declines exponentially with therapy. Expression levels can be
      independently correlated with outcomes.

PMID- 17496537
TI  - Simpler and equitable allocation of kidneys from postmortem donors primarily
      based on full HLA-DR compatibility.
AB  - BACKGROUND: The introduction of human leukocyte antigen (HLA)-matching in
      nonliving kidney transplantation has resulted into a better graft outcome, but
      also in an increase of waiting time, especially for patients with rare HLA
      phenotypes. We addressed the question of the differential influence of HLA-DR
      matching versus HLA-A,B in clinical kidney transplantation. METHODS: We used
      Kaplan-Meier product limit method to estimate survival rates, and Cox
      proportional hazard regression for the estimation of relative risks (Hazard
      ratios) for different variables. RESULTS: A single center study (n=456
      transplants, performed between 1985 and 1999) showed that full HLA-DR
      compatibility leads to a lower incidence of biopsy confirmed acute rejections in
      the first 180 posttransplantation days. These results were substantiated using
      the Eurotransplant database (n=39,205 transplants performed between 1985 and
      2005) where graft survival in the full HLA-DR compatible group was significantly
      better than in the incompatible. An additional positive effect of HLA-A,B
      matching was only found in the full HLA-DR compatible group. In both studies, the
      introduction of a single HLA-DR incompatibility eliminates the HLA-A,B matching
      effect. CONCLUSIONS: We propose to allocate postmortem kidneys only to patients
      with full HLA-DR compatibility, and use HLA-A,B compatibility as an additional
      selection criterion. All patients, irrespective of their ethnic origin, will
      profit since the polymorphism of HLA-DR is by far lower than that of HLA-A,B.
      Excessive kidney travel and cold ischemia time will be significantly reduced.

PMID- 17496538
TI  - Alcohol use in donors is a protective factor on recipients' outcome after heart
      transplantation.
AB  - OBJECTIVE: The outcome of heart transplantation is highly influenced by good
      donor selection. Because a history of alcoholism is prevalent among potential
      heart donors, we sought to explore the effect of alcohol use in donors on the
      outcome of heart transplantation in the recipient. METHOD: A total of 437
      consecutive patients underwent heart transplantation from January 2002 through
      September 2005. Patients' files were retrospectively studied. Mean follow-up
      period was 3.14+/-1.9 years (range, 3 days to 6.5 yrs). The cohort was divided
      into two subgroups. The alcoholic donor group (ADG) included 98 of 421 patients
      and the nonalcoholic donor group (NADG) included 323 of 421 patients. Mean age
      was 35.3+/-11.4 yrs (range, 18-66) for the ADG and 33+/-12.2 yrs (range, 18-62)
      for the NADG. RESULTS: Mortality among the ADG was 7 of 98 (7.1%) and for NADG
      was 55 of 323 (17.1%) (P=0.015). The mean interval time between transplant and
      mortality was, for ADG, 27.7+/-20.6 months (range, 0.07-51) and for NADG, 16.4+/
      19.6 months (range, 0.14-73) (P=0.031). Survival rate was significantly higher
      among the ADG at 72.8+/-1.9 months compared with NADG at 66.2+/-1.5 months
      (P=0.019). Overall rejection rate was 22 of 421 (5.2%); rejection rate was 17 of
      323 (5.2%) in NADG and 5 of 98 (5.1%) in ADG. Rejection free survival was 74.6+/
      0.85 with no significant difference between the two groups (P=0.85). CONCLUSION:
      The chronic alcoholism of donors was found to be a protective factor regarding
      the outcome after heart transplantation. Significant differences were found in
      mortality rate and survival after heart transplantation between the ADG and NADG.
      These data support the fact that it is safe to use donors' hearts regardless of a
      history of alcoholism.

PMID- 17496539
TI  - CD154 blockade, sirolimus, and donor-specific transfusion prevents renal
      allograft rejection in cynomolgus monkeys despite homeostatic T-cell activation.
AB  - BACKGROUND: CD154-specific antibodies have been shown to prevent acute rejection
      in many preclinical models including nonhuman primates (NHPs). However, they have
      been ineffective in pilot clinical trials, suggesting a need for more robust
      preclinical analysis. One factor affecting the disparate results may be related
      to the recipient's immune activation state. Specifically, adult humans have a
      high percentage of memory-phenotype T cells compared to young animals.
      Postdepletional homeostatic repopulation has been shown to enrich for memory
      phenotype T cells and interfere with CD154-based therapies in rodents. METHODS:
      We developed a NHP model nonspecifically enriched for peripheral memory-phenotype
      T cells. Thymectomized cynomolgus macaques underwent depletion with polyclonal
      anti-thymocyte globulin followed by repopulation. Peripheral phenotype was
      serially determined using polychromatic flow cytometry. In vitro response to
      donor and environmental antigens was also confirmed before and after
      manipulation. We then tested a regimen previously successful in rhesus monkeys
      combining anti-CD154, sirolimus, and donor-specific blood transfusion (DST), in a
      second primate species with and without the provocation of increased peripheral
      homeostatic T-cell activation. RESULTS: Monkeys that were thymectomized (n=3) and
      depleted recovered via homeostatic repopulation with a repertoire enriched for
      cells with a memory surface phenotype compared to unmanipulated controls (n=3).
      Despite a repertoire markedly enriched for memory-phenotype cells, the regimen
      effectively prevented acute rejection for the duration of therapy. CONCLUSIONS:
      Cynomolgus monkeys can be rendered memory phenotype enriched using homeostatic
      repopulation. Despite a generally activated T-cell repertoire, anti-CD154,
      sirolimus, and DST effectively prevents rejection in cynomolgus monkeys.

PMID- 17496540
TI  - Spleen plays an important role in maintaining tolerance after removal of the
      vascularized heart graft.
AB  - BACKGROUND: This study addresses the question of the mechanism for maintaining
      tolerance to donor alloantigen in the absence of antigen and the role of
      secondary lymphoid tissues. METHODS: Depleting anti-CD4 antibody administration
      in conjunction with allogeneic heart transplantation generates donor-specific
      operational tolerance. Primary C57BL/6 heart grafts were transplanted into the
      neck cavity of the anti-CD4 antibody pretreated C3H/He mice. At day 50,
      functioning heart grafts were removed from tolerant mice. At day 100, a secondary
      C57BL/6 or a third-party heart was transplanted into the abdomen. RESULTS: Anti
      CD4 antibody therapy induced CD4CD25 regulatory T cells by 50 days after
      transplantation, as depleting anti-CD25 treatment in tolerant mice abrogated
      graft prolongation when spleen leukocytes were adoptively transferred to
      syngeneic mice. Tolerance was maintained by CD4CD25 regulatory T cells via a CTLA
      4 signal at 100 days, even after removal of the primary graft at day 50.
      Administration of anti-CD25 antibody immediately after removal of the primary
      graft did not break tolerance, as five out of six second allografts transplanted
      at day 100 were accepted. Anti-CD25 antibody therapy in conjunction with
      splenectomy, but not thymectomy, immediately after removal of primary heart
      grafts at day 50 broke tolerance at day 100; all allografts were rejected.
      CONCLUSION: The spleen is important in maintaining CD4CD25 regulatory T cells
      after primary allograft removal.

PMID- 17496541
TI  - Low molecular weight fucoidan prevents neointimal hyperplasia after aortic
      allografting.
AB  - BACKGROUND: Fucoidan, a new low molecular weight sulfated polysaccharide (LMWF),
      has previously been shown to mobilize bone marrow-derived progenitors cells via
      stimulation of stromal derived factor (SDF)-1 release. Mobilized progenitor cells
      have been suggested to repair intimal lesions after immune-mediated endothelial
      injury and thus prevent intimal proliferation. The aim of this study was to
      evaluate the effect of LMWF treatment in a rat aortic allograft model of
      transplant arteriosclerosis (TA). METHODS: Aortic grafts were performed in Brown
      Norway (BN, donor) and Lewis (Lew, recipient) rats. The recipient rats were
      treated with LMWF (5 mg/kg/day) and sacrificed at 30 days. To determine the role
      of SDF-1 in mediating the effects of LMWF, a specific inhibitor of the SDF-1
      receptor CXCR4, AMD 3100 (20 microg/kg/day), was used. The grafted segments were
      evaluated by morphometric (histochemical) analyses. RESULTS: Untreated aortic
      allografts exhibited severe intimal proliferation, indicative of TA. In contrast,
      LMWF treatment significantly prevented allograft intimal proliferation as
      compared with controls (5.7+/-3 vs. 66.2+/-6 microm, P<0.01) and permitted a
      normalization of the intima/media ratio (0.1+/-0.1 vs. 1.7+/-0.3, P<0.01).
      Further, LMWF treatment stimulated allograft reendothelialization, as evidenced
      by strong intimal endothelial nitric oxide synthase antibody and CD31 signals.
      Unexpectedly, AMD treatment failed to prevent the protective effect of LMWF on
      intimal thickening and AMD treatment alone was found to reduced intimal
      proliferation in allografts. CONCLUSIONS: We found that LMWF treatment reduced
      intimal thickness and induced the presence of an endothelial cell lining in the
      vascular graft at 30 days. Our findings may suggest a novel therapeutic strategy
      in the prevention of TA.

PMID- 17496542
TI  - A single minor histocompatibility antigen encoded by UGT2B17 and presented by
      human leukocyte antigen-A*2902 and -B*4403.
AB  - BACKGROUND: T-cell responses to minor histocompatibility antigens are mediators
      of graft-versus-host disease and organ graft rejection. We previously identified
      a human minor histocompatibility antigen that is recognized by CD8 cytotoxic T
      lymphocytes (CTLs) and encoded by the UDP glycosyltransferase 2 family,
      polypeptide B17 (UGT2B17) gene, which is highly expressed in the liver, colon,
      and small intestine. The UGT2B17 is presented by human leukocyte antigen (HLA)
      A*2902, and the immunogenicity of this minor histocompatibility antigen results
      from differential protein expression in donor and recipient cells as a
      consequence of a UGT2B17 gene deletion. METHODS: An HLA-B*4403-restricted CD8 CTL
      clone was isolated from the same hematopoietic stem cell transplant recipient
      that exhibited an HLA-A*2902-restricted UGT2B17-specific response. The minor
      histocompatibility antigen recognized by the HLA-B*4403-restricted clone was
      identified, and the ability of the peptide to be presented by HLA-B*4402 was
      examined. RESULTS: The HLA-B*4403-restricted CTL clone recognized a peptide
      encoded by UGT2B17, which is identical to the peptide presented by HLA-A*2902.
      Peptide binding assays revealed this UGT2B17 peptide binds with comparable
      affinity to HLA-B*4402 as to HLA-B*4403. This patient had acute graft-versus-host
      disease involving liver and gastrointestinal tract, suggesting the T-cell
      response directed against UGT2B17 is involved in graft-versus-host disease.
      CONCLUSIONS: A single peptide encoded by UGT2B17 can be presented by HLA-A*2902,
      B*4402 and B*4403, and may serve as an immunodominant minor histocompatibility
      antigen in individuals with these HLA alleles that undergo transplantation of
      stem cells or organ grafts from UGT2B17 disparate donors.

PMID- 17496543
TI  - Improvement of kidney failure with fetal kidney precursor cell transplantation.
AB  - BACKGROUND: Current therapies for end-stage renal disease have severe
      limitations. Dialysis is only a temporary treatment and does not restore kidney
      function. Transplantation is limited by donor organ shortage and immune-related
      problems. Here, we show that the transplantation of fetal kidney precursor cells
      reconstitutes kidney tissues, reduces uremic symptoms, and provides life-saving
      metabolic support in kidney failure animal models. METHODS: Kidney failure was
      surgically induced by resecting kidneys, leaving approximately 1/6 of the total
      kidney mass (5/6 nephrectomy). Fetal kidney precursor cells were isolated from
      metanephroi of E17.5 rat fetuses using collagenase/dispase digestion. Five weeks
      after the nephrectomy procedure, isolated fetal kidney precursor cells were
      transplanted under the kidney capsule of rats using fibrin gel matrix. Six and
      ten weeks after transplantation, animals were analyzed biochemically and the
      grafts were retrieved for histological analyses. RESULTS: Five weeks after the
      nephrectomy, glomerular hypertrophy, and increased blood urea nitrogen and serum
      creatinine levels were observed. The cell transplantation into the kidneys of
      kidney failure-induced rats resulted in kidney tissue reconstitution and the
      transplanted cells were observed in the reconstitution region of the kidneys as
      evidenced by the presence of fluorescently labeled cells. In addition,
      biochemical parameters from serum and urine samples showed improved kidney
      functions compared with non-treated group without severe immune response after
      ten weeks. CONCLUSION: Transplanting fetal kidney precursor cells showed the
      potential for the partial augmentation of kidney structure and function in the
      treatment of kidney failure.

PMID- 17496544
TI  - Anti-LFA-1 improves pig islet xenograft function in diabetic mice when long-term
      acceptance is induced by CTLA4Ig/anti-CD40L.
AB  - BACKGROUND: It has been previously demonstrated that addition of anti-LFA-1 to a
      combination of CTLA4Ig and anti-CD40L induces the permanent acceptance of
      dopaminergic fetal pig xenografts when transplanted into the brain of wild-type
      mice. The purpose of this study was to test whether this costimulation blockade
      also can induce acceptance of adult pig islets transplanted to C57BL/6 mice with
      streptozotocin-induced diabetes. METHODS: Recipients were treated with
      CTLA4Ig/anti-CD40L+/-anti-LFA-1 or isotype control antibodies during the first
      week after transplantation. Half of the costimulation blockade-treated recipients
      had their grafts removed after 8 weeks. The other half was observed up to 5
      months. RESULTS: Recipients treated with CTLA4Ig/anti-CD40L/anti-LFA-1 had
      significantly lower blood glucose and gained more weight than CTLA4Ig/anti-CD40L
      treated recipients. CTLA4Ig/anti-CD40L-treated recipients exhibited unstable
      blood glucose. IPGTT of these recipients revealed a slow recovery to normal blood
      glucose levels at week 4. In comparison, CTLA4Ig/anti-CD40L/anti-LFA-1 treated
      recipients exhibited a significantly superior glucose clearance. CTLA4Ig/anti
      CD40L+/-anti-LFA-1 treated recipients did not produce anti-pig IgG, whereas
      control antibody-treated mice did. CD4+ T cells from costimulation blockade
      treated recipients proliferated less than CD4+ T cells from control antibody
      treated mice when co-cultured with syngeneic antigen presenting cells loaded with
      pig islet antigens. CONCLUSIONS: CTLA4Ig/anti-CD40L/anti-LFA-1-treated recipients
      had superior islet function compared with CTLA4Ig/anti-CD40L-treated recipients.
      However, both costimulation blockade regimens led to islet graft acceptance up to
      5 months after a 1-week treatment.

PMID- 17496545
TI  - Alemtuzumab depletes dendritic cells more effectively in blood than in skin: a
      pilot study in patients with chronic lymphocytic leukemia.
AB  - The antibody alemtuzumab (anti-CD52) is effective in preventing acute graft
      versus-host disease (GvHD) after allogeneic hematopoietic stem cell
      transplantation (aHSCT). As well as depleting donor T cells, alemtuzumab may also
      work by targeting host dendritic cells (DC). To determine whether this second
      mechanism of action is significant, we investigated the effects of intravenous
      alemtuzumab by comparing skin and blood DC numbers of patients with chronic
      lymphocytic leukemia, before and after a 4-week course of alemtuzumab treatment.
      Although skin DC express CD52, the epitope is only weakly detectable and their
      numbers were not consistently reduced by alemtuzumab. In contrast, circulating
      blood DC, with stronger CD52 expression, were invariably diminished by
      alemtuzumab. Because DC depletion in the transplant recipient remains a promising
      approach for GvHD prophylaxis and therapy, more potent techniques, such as an
      antibody of different specificity, may be required for effective DC eradication
      in GvHD target organs.

PMID- 17496546
TI  - Simultaneous vascularized bone marrow transplantation to promote acceptance of
      hind limb allografts and its effects on central and peripheral chimerism.
AB  - Administration of donor bone marrow (BM) cells can improve the outcome of
      transplantation. The ability of donor vascularized bone marrow transplantation
      (VBM) to provide an ongoing source of donor cells and improve survival in a
      rigorous rat model of hind limb transplantation (HLTX) was investigated. HLTX
      were performed between Brown Norway (BN) donors and Lewis recipients in three
      groups: HLTX; HLTX plus intravenous donor BM cells and HLTX plus simultaneous VBM
      transplantation. Animals received 12 weeks triple immunosuppression. Survival was
      compared at 4 months and donor chimerism was evaluated. Simultaneous VBM
      transplantation led to slight but nonsignificant prolongation of survival
      (P=0.056). Donor cells in the VBM were eventually replaced by recipient and there
      was no long-term increase in chimerism. Few donor cells were observed in thymus.
      Simultaneous VBM transplantation showed a trend for improved survival of HLTX
      however the VBM failed to provide a sustained increase in chimerism.

PMID- 17496547
TI  - Rituximab therapy for acute humoral rejection after kidney transplantation.
AB  - A pilot study was performed on eight consecutive renal-transplant (RT) patients
      presenting with acute humoral rejection (AHR) to assess the efficacy of
      monoclonal anti-B cell antibodies, such as rituximab (375 mg/m weekly) for 3 to 5
      consecutive weeks, in addition to plasma exchange (PE), steroids, mycophenolate
      mofetil, and tacrolimus. AHR was associated with increased serum creatinine, the
      appearance of donor-specific alloantibodies (DSA), and the presence of C4d in a
      transplant biopsy. After a follow-up of 10 months (range 7-23), patient and graft
      survivals were 100% and 75%, respectively. Renal function improved in six cases
      in which serum creatinine decreased from 297+/-140 to 156+/-53 micromol/L
      (P=0.015); graft loss occurred in two cases; and four patients had infectious
      complications. At last follow-up, DSA had disappeared or decreased in four cases.
      Rituximab therapy, in addition to PE, might be of benefit for RT patients
      presenting with AHR.

PMID- 17496548
TI  - Successful engraftment in reduced-intensity cord blood transplantation (CBT) as a
      salvage therapy for graft failure after primary CBT in adults.

PMID- 17496549
TI  - In response to transplantation 2005; 79: 1236-40. Laparoscopic versus open living
      donor nephrectomy: experiences from a prospective, randomized, single-center
      study focusing on donor safety.

PMID- 17496550
TI  - Late introduction of sirolimus induces anemia in renal transplant recipients.

PMID- 17496551
TI  - Alternative strategy for overcoming ABO incompatibility.

PMID- 17496554
TI  - Analysis of anatomic periarticular tibial plate fit on normal adults.
AB  - Implant manufacturers are producing anatomically contoured periarticular plates
      to improve the treatment of proximal tibia fractures. We assessed the accuracy of
      the designation anatomic. We applied eight-hole medial and lateral anatomically
      contoured periarticular plates to 101 cadaveric tibiae. The tibiae and the plate
      fits were mapped, quantified, and analyzed using a MicroScribe G2LX digitizer,
      Rhinoceros software, and MATLAB software. By corresponding the clinical
      appearance of good fit with our digital findings, we created numerical criteria
      for plate fit in three planes: coronal (volume of free space between the plate
      and bone), sagittal (alignment with the tibial plateau and shaft), and axial
      (match in curvature between the proximal horizontal part of the plate and the
      tibial plateau). An anatomic fit should mirror the shape of the tibia in all
      three planes, and only four medial and four lateral plate fits qualified.
      Recognizing and understanding the substantial variations in fit that exist
      between anatomically contoured plates and the tibia may help lead to a more
      stable fixation and prevent malreduction of the fracture and/or soft tissue
      impingement.

PMID- 17496555
TI  - Chronic recurrent multifocal osteomyelitis: a concise review and genetic update.
AB  - Chronic recurrent multifocal osteomyelitis is an autoinflammatory disorder
      characterized by bone pain and fever, a course of exacerbations and remissions,
      and a frequent association with other inflammatory conditions. Because its
      etiology is largely unknown, the diagnosis is still based on clinical criteria;
      treatment is empiric and not always successful. The diagnosis is supported by the
      presence of osteolytic lesions with surrounding sclerosis apparent on
      radiographs, and silent asymptomatic lesions frequently appear on nuclear scans.
      The histologic findings in bone biopsies are nonspecific, showing inflammatory
      changes with granulocytic infiltration. Several observations suggest the
      contribution of genetic factors to the etiology of chronic recurrent multifocal
      osteomyelitis. Indeed, mutations in LPIN2 cause a syndromic form of chronic
      recurrent multifocal osteomyelitis known as Majeed syndrome, while mutations in
      pstpip2 cause a murine form of the disorder. The roles played by LPIN2 and the
      human homolog of pstpip2, PSTPIP2, in the etiology of chronic recurrent
      multifocal osteomyelitis are uncertain but are currently being investigated. We
      emphasize the need to validate diagnostic clinical criteria and develop new
      pathogenesis-based targeted therapy.

PMID- 17496556
TI  - Competing events influence estimated survival probability: when is Kaplan-Meier
      analysis appropriate?
AB  - The Kaplan-Meier estimator is the current method for estimating the probability
      of an event to occur with time in orthopaedics. However, the Kaplan-Meier
      estimator was designed to estimate the probability of an event that eventually
      will occur for all patients, ie, death, and this does not hold for other
      outcomes. For example, not all patients will experience hip arthroplasty
      loosening because some may die first, and some may have their implant removed to
      treat infection or recurrent hip dislocation. Such events that preclude the
      observation of the event of interest are called competing events. We suggest the
      Kaplan-Meier estimator is inappropriate in the presence of competing events and
      show that it overestimates the probability of the event of interest to occur with
      time. The cumulative incidence estimator is an alternative approach to Kaplan
      Meier in situations where competing risks are likely. Three common situations
      include revision for implant loosening in the long-term followup of
      arthroplasties or implant failure in the context of limb-salvage surgery or
      femoral neck fracture.

PMID- 17496557
TI  - Timeliness of appropriate antibiotics in hand infections.
AB  - We retrospectively reviewed the charts of 110 patients to determine if there was
      a difference in the time to appropriate antibiotic treatment between methicillin
      resistant staphylococcus aureus (MRSA) and non-MRSA hand infections. Patients
      were included in the study only if they had a culture-positive hand infection and
      received antibiotic treatment. Thirty-two patients (18 male and 14 female) with
      an average age of 39.1 years (range, 6 months-72 years) met the inclusion
      criteria. We recorded patient age, gender, date of presentation, time to
      receiving any antibiotic, time to final culture results, and time to receiving
      culture-appropriate antibiotics. The overall prevalence of MRSA infection was
      34%. When compared to those with non-MRSA infections, patients with MRSA hand
      infections experienced a substantial delay in receiving appropriate antibiotics.

PMID- 17496558
TI  - A modified transfemoral approach using modular cementless revision stems.
AB  - The transfemoral approach in its traditional form, using a nonmodular Wagner self
      locking revision stem, has the disadvantages of a less predictable union rate of
      the bony flap and a high rate of stem subsidence. To investigate whether this
      situation can be improved by using a modified transfemoral approach and modular
      curved cementless revision stems, we prospectively analyzed 68 hip revisions and
      followed them clinically and radiographically for a minimum of 24 months (mean +/
      standard deviation, 32.4 +/- 11.2 months). One year after the operation, the
      osteotomy showed bony consolidation in all but one case (98.5%). We noted
      subsidence in six cases (8.8%) and two of these stems became loose. In all of
      these cases, the circular fixation zone of the stem in the isthmus of the femur
      was less than 3 cm. The Harris hip score improved continuously from 41.4 +/- 14.5
      points preoperatively to 85.9 +/- 14.6 points 24 months postoperatively. The
      modified transfemoral approach in combination with a curved, modular revision
      stem showed reproducibly good results concerning union of the bony flap and
      subsidence of the stem if the fixation zone was not less than 3 cm.

PMID- 17496559
TI  - Dynamic biomechanics correlate with histopathology in human tibial cartilage: a
      preliminary study.
AB  - Improved staging of cartilage degeneration is required, particularly during early
      stages when minimal surface damage is visible arthroscopically. Degradation of
      articular cartilage extracellular matrix, resulting from degenerative changes
      associated with osteoarthritis, can influence its functional properties.
      Cartilage mechanical properties therefore may provide a quantitative method for
      monitoring degenerative change in this tissue. We determined whether dynamic
      mechanical properties of cartilage (effective shear modulus and phase lag)
      measured with a handheld indenter correlated with histopathology scores,
      proteoglycan, and collagen content or expression of chondrocyte-specific
      (aggrecan, collagen II) or dedifferentiation (collagen I and III) genes in human
      osteoarthritic cartilage with International Cartilage Repair Society scores of 0
      to 1. We observed an association between the histopathologic stage of cartilage
      disease and dynamic shear modulus and phase lag. In contrast, there generally was
      a poor relationship between cartilage biomechanical properties and biochemistry
      with the only noteworthy correlation being between shear modulus and collagen.
      Phase lag but not shear modulus correlated with gene expression. These data
      support the potential of dynamic indentation for assessing the stage of cartilage
      degeneration in tissue with minimal gross surface damage.

PMID- 17496560
TI  - The spread of HIV-1 subtypes B and CRF01_AE among injecting drug users in
      Bangkok, Thailand.
AB  - The HIV epidemic among injecting drug users (IDUs) in Bangkok was initially
      dominated by HIV subtype B and later by the recombinant CRF01_AE. The present
      study investigates the distribution of the 2 variants in time and how it is
      affected by changes in injecting risk behavior and treatment. A mathematic model
      describing the spread of HIV subtype B and CRF01_AE among IDUs was developed, and
      data from the AIDSVAX B/E cohort of IDUs in Bangkok were used. From the model, it
      was calculated that during 1999 to 2003, the annual incidence of HIV was around
      0.6 and 2.7 to 3.9 infections per 100 person-years for subtype B and CRF01_AE,
      respectively. Of the new infections, 18% and 72% are first infections with
      subtype B and CRF01_AE, respectively, and 9% are superinfections. With increases
      in risk behavior, the fraction of superinfections rises. If treatment reduces the
      infectivity of CRF01_AE more than that of subtype B, the fraction of subtype B
      infections should increase. Subtype B should remain prevalent in a small but
      considerable fraction of the population for a long time. Changes in risk behavior
      and the introduction of treatment may alter the distribution of subtypes, but
      CRF01_AE should remain dominant.

PMID- 17496561
TI  - Virologic characterization of HIV type 1 with a codon 70 deletion in reverse
      transcriptase.
AB  - We identified a deletion at codon 70 (Delta70) of HIV-1 reverse transcriptase
      (RT) occurring together with L74V and Q151M mutations in a sample from a
      tenofovir (TFV)- and abacavir (ABC)-treated patient with extensive prior
      antiretroviral treatment. To investigate the characteristics of this mutant, we
      studied the drug susceptibility, relative infectivity, and fitness of viruses
      carrying Delta70 and associated RT mutations. The Delta70, L74V, and Q151M
      mutations were introduced into Hxb2 RT by site-directed mutagenesis and expressed
      in HIV-1 recombinants. The Delta70 mutation increased resistance to lamivudine
      and emtricitabine alone and in combination with various resistance mutations and
      augmented resistance to ABC and didanosine when present together with L74V. A
      recombinant virus expressing RT from the original clinical viral sample (Delta70
      PRT) exhibited greater fitness than one in which the deletion had been repaired
      (K70-PRT). The Delta70 mutation also increased fitness of Hxb2 wild-type and 74V
      and Q151M mutants. Recombinants carrying Delta70-PRT showed greater relative
      infectivity in the presence of ABC (but not TFV) compared with K70-PRT
      recombinants. These results show that Delta70 enhances resistance to certain
      purine and pyrimidine analogues and contributes to multinucleoside resistance in
      the appropriate viral genetic background.

PMID- 17496562
TI  - The evolving cost of HIV in South Africa: changes in health care cost with
      duration on antiretroviral therapy for public sector patients.
AB  - A retrospective costing study of 212 patients enrolled in a nongovernmental
      organization-supported public sector antiretroviral treatment (ART) program near
      Cape Town, South Africa was performed from a health care system perspective.
      gamma-Regression was used to analyze total costs in 3 periods: Pre-ART (median
      length=30 days), first 48 weeks on ART (Year One), and 49 to 112 weeks on ART
      (Year Two). Average cost per patient Pre-ART was $404. Average cost per patient
      year of observation was $2502 in Year One and $1372 in Year Two. The proportion
      of costs attributable to hospital care fell from 70% Pre-ART to 24% by Year Two;
      the proportion attributable to ART rose from 31% in Year One to 55% in Year Two.
      In multivariate analysis, Pre-ART and Year One costs were significantly lower for
      asymptomatic patients compared with those with AIDS. Costs were significantly
      higher for those who died Pre-ART or in Year One. In Year Two, only week 48 CD4
      cell count and being male were significantly associated with lower costs. This
      analysis suggests that the total cost of treatment for patients on ART falls by
      almost half after 1 year, largely attributable to a reduction in hospital costs.

PMID- 17496563
TI  - Improvement in survival among symptomatic AIDS patients by exposure category in
      Sao Paulo.
AB  - OBJECTIVE: The study assesses AIDS survival time per AIDS-case definition and
      exposure category in Sao Paulo State, Brazil during the periods 1992 to 1995 and
      1998 to 2001. METHODS: Case-fatality rate per AIDS case, Cox proportional hazards
      analysis, and Kaplan-Meier survival time. RESULTS: The case-fatality rate per
      AIDS case in 1998 to 2001 was 37.6% for symptomatic (Centers for Disease Control
      and Prevention/modified and/or Paho/Caracas) and 9.7% for the Brazilian
      asymptomatic CD4 count<350 cells/mm3 AIDS-case definitions. Heterosexual/female
      patients were diagnosed earlier and presented the lowest case-fatality rate,
      followed by homosexual/male patients, heterosexual/male patients, and injecting
      drug users. In the multivariate Cox proportional hazards model, the period of
      diagnosis (hazard ratio=2.66; 95% confidence interval [CI]: 2.58 to 2.74) and
      AIDS-case definition (hazard ratio=4.48; 95% CI: 4.53 to 5.16) were strong
      predictors of survival. For the total AIDS cases, excluding death definition and
      undetermined exposure category, the estimated first quarter survival time
      improved from 4 months in 1992 to 1995 to 50 months in 1998 to 2001. Considering
      only the symptomatic AIDS-case definition, however, the improvement was from 4
      months in the period 1992 to 1995 to 14 months in the period 1998 to 2001.
      CONCLUSION: The survival improvement in Sao Paulo State was attributable to the
      introduction of antiretroviral therapy with free universal access in 1996 and to
      earlier diagnosis associated with the introduction in 1998 of the Brazilian
      asymptomatic CD4 count<350 cells/mm3 AIDS-case definition with superior
      sensitivity compared with the symptomatic AIDS-case definitions.

PMID- 17496564
TI  - Epidemiologic and evolutionary trends of HIV-1 CRF31_BC-related strains in
      southern Brazil.
AB  - BACKGROUND: To evaluate the impact of HIV-1 CRF31_BC in the southern Brazilian
      HIV epidemic. METHODS: Blood plasma from 284 patients was collected from July
      2002 to January 2003 at 2 reference HIV/AIDS centers in southern Brazil. Viral
      protease and reverse transcriptase (RT) genomic regions were amplified by RT
      polymerase chain reaction, sequenced, and subtyped. Evolutionary analyses were
      performed to estimate the CRF31_BC most recent common ancestor and its population
      growth rate with BEAST version 1.3. RESULTS: CRF31_BC was responsible for 7.4% of
      infections. The average time of HIV diagnosis and the proportion of patients on
      antiretroviral treatment were shorter for CRF31_BC and subtype C than for subtype
      B. CRF31_BC was found as early as in 1990 in the Brazilian epidemic. Evolutionary
      analysis of CRF31_BC revealed that it appeared immediately after the introduction
      of subtype C in Brazil and has been growing at a similar rate as subtype C.
      CONCLUSIONS: CRF31_BC plays an important role in the HIV epidemic of southern
      Brazil, and its prevalence has increased throughout the years. This circulating
      recombinant form corresponds to approximately 25% of total HIV isolates in this
      region in 2004. Understanding the cause of this spread is important for public
      health strategies in Brazil and in Latin America.

PMID- 17496567
TI  - Fusarium infections of the skin.

PMID- 17496565
TI  - Transient viremia, plasma viral load, and reservoir replenishment in HIV-infected
      patients on antiretroviral therapy.
AB  - When antiretroviral therapy (ART) is administered for long periods to HIV-1
      infected patients, most achieve viral loads that are "undetectable" by standard
      assay methods (ie, HIV-1 RNA <50 copies/mL). Despite sustaining viral loads lower
      than the level of detection, a number of patients experience unexplained episodes
      of transient viremia or viral "blips." We propose that transient activation of
      the immune system by infectious agents may explain these episodes of viremia.
      Using 2 different mathematical models, one in which blips arise because of target
      cell activation and subsequent infection and another in which latent cell
      activation generates blips, we establish a nonlinear (power law) relationship
      between blip amplitude and viral load (under ART) that suggest blips should be of
      lower amplitude, and thus harder to detect, as increasingly potent therapy is
      used. This effect can be more profound than is predicted by simply lowering the
      baseline viral load from which blips originate. Finally, we suggest that sporadic
      immune activation may elevate the level of chronically infected cells and
      replenish viral reservoirs, including the latent cell reservoir, providing a
      mechanism for recurrent viral blips and low levels of viremia under ART.

PMID- 17496568
TI  - Acute bacterial skin infections and cellulitis.
AB  - PURPOSE OF REVIEW: Acute bacterial skin infections are very common, with various
      presentations and severity. This review focuses on deep skin infections. We
      separate acute nonnecrotizing infections of the hypodermis (erysipelas), forms
      with abscesses or exudates and necrotizing fasciitis. These three types actually
      differ in risk factors, bacteriology, treatment and prognosis. RECENT FINDINGS:
      Leg erysipelas/cellulitis occurs in more than one person/1000/year. It remains
      mainly due to streptococci. Foot intertrigo is an important risk factor.
      Necrotizing fasciitis is much rarer and usually occurs in patients with chronic
      diseases. Staphylococci, especially community-acquired methicillin-resistant
      strains in some areas, play a growing role in the intermediate form of cellulitis
      with abscesses and exudates. For erysipelas or noncomplicated cellulitis,
      antibiotic treatment at home, when feasible, is much less expensive and as
      effective as hospital treatment. Intermediate cases with collections and exudates
      often require surgical drainage. For necrotizing fasciitis early surgery remains
      essential in order to decrease the mortality rate. SUMMARY: Antibiotic treatment
      of deep skin infections must be active on streptococci; the choice of a larger
      spectrum of activity depends on clinical presentation, risk factors and the
      burden of methicillin-resistant staphylococci in the environment.

PMID- 17496569
TI  - Infection following soft tissue injury: its role in wound healing.
AB  - PURPOSE OF REVIEW: Wound infection has always been an unconquered problem
      temporarily improved with the discovery of antibiotics but now struggling with an
      epidemic of resistant organisms. Wound healing has become a popular sub
      speciality for the doctor and allied health professional working in the
      laboratory or at the bedside. It is a field with many new journals and frequent
      congresses that publish elaborate proceedings. These have been examined for this
      review. RECENT FINDINGS: Measurement of infection remains elusive. A clear
      difference between contamination and infection is difficult to delineate. In the
      era of the HIV/AIDS epidemic attention is drawn to host factors, which when
      attended to are as effective in suppressing infection as antisepsis. The
      bacterial capacity to put on a protective coat known as biofilm is a newly
      investigated system. SUMMARY: Antisepsis and antibiotics continue to provide a
      wealth of studies and some new technology. The evidence base, as examined by
      Cochrane systematic reviews, suggests that our strategy for preventing and
      dealing with infection of wounds needs further refinement.

PMID- 17496570
TI  - Infectious keratitis.
AB  - PURPOSE OF REVIEW: Infectious keratitis is a medical emergency. Improper
      management can lead to marked loss of vision. This review identifies recent
      trends in the study of infectious keratitis. RECENT FINDINGS: A multicountry
      outbreak of Fusarium keratitis emphasizes that contact lens wear is a major risk
      factor for infectious keratitis. Acanthamoeba and fungal keratitis are the most
      expensive forms of infectious keratitis to treat. Noninvasive methods and
      molecular techniques have improved diagnosis of infectious keratitis. Fortified
      topical antibiotics and fluoroquinolones are still the mainstay of bacterial
      keratitis therapy. Voriconazole and new routes of administration of conventional
      antifungals appear promising for fungal keratitis. Antivirals and amelioration of
      host inflammatory response are promising for viral keratitis; the host response
      is also crucial in pathogenesis of Pseudomonas aeruginosa keratitis. Trauma
      induced bacterial and fungal keratitis and contact lens-associated keratitis are
      preventable entities. SUMMARY: Improved modalities of diagnosis and treatment
      have improved the outcome of infectious keratitis, but therapy of acanthamoebal,
      fungal and P. aeruginosa keratitis is still a challenge. Effective strategies
      must neutralize potential risk factors and counter host response overactivity
      without impairing killing of infecting microorganisms. Trauma-induced bacterial
      and fungal keratitis can be prevented.

PMID- 17496571
TI  - New fungal nail infections.
AB  - PURPOSE OF REVIEW: The number of people affected by onychomycosis continues to
      increase. The prevalence of different pathogens in different areas depends on
      several factors, such as climate, geography and migration. We reviewed the recent
      literature to identify new agents responsible for onychomycosis. RECENT FINDINGS:
      Recent studies performed in different countries are not only reporting molds and
      yeasts as contaminants, but are increasingly reporting them as pathogens.
      Infection by novel agents is also being reported, although the individual cases
      do not necessarily indicate that these are emerging agents. SUMMARY: Clinicians
      should bear in mind the increased number of case series reporting the role of
      molds and yeasts in onychomycosis, and should not treat the disease without first
      examining the mycology results. The question remains as to whether these agents
      are truly new fungi responsible for onychomycosis, or whether improvement of
      diagnostic techniques and increasing reference to such species in the literature
      has resulted in better identification of such agents.

PMID- 17496572
TI  - Management of mycetoma: major challenge in tropical mycoses with limited
      international recognition.
AB  - PURPOSE OF REVIEW: The present review highlights an orphan infectious disease in
      alarming need of international recognition. While money is being invested to
      develop new broad-spectrum antimicrobial drugs to treat infection in general,
      improvement in the management of complicated infections such as mycetoma receives
      little support. RECENT FINDINGS: Many case presentations describe single-center
      experience in the management of mycetoma. Unfortunately, randomized and blinded
      clinical studies into the efficacy of antimicrobial treatment are desperately
      lacking. Response to medical treatment is usually better in actinomycetoma than
      eumycetoma. Eumycetoma is difficult to treat using current therapies. Surgery in
      combination with azole treatment is the recommended regimen for small eumycetoma
      lesions in the extremities. Bone involvement complicates clinical management,
      leaving surgical amputation as the only treatment option. Although clinical
      management has not received major attention recently, laboratory technology has
      improved in areas of molecular diagnosis and epidemiology. SUMMARY: Management of
      mycetoma and laboratory diagnosis of its etiological agents need to be improved
      and better implemented in endemic regions. Optimized therapeutic approaches and
      more detailed epidemiological data are urgently needed. It is vital to initiate
      multicenter collaborations on national and international levels to develop
      consensus clinical score sheets and state-of-the-art treatment regimens for
      mycetoma patients.

PMID- 17496573
TI  - Transmission of human herpesvirus 8: an update.
AB  - PURPOSE OF REVIEW: Human herpesvirus 8 is associated with neoplastic diseases in
      the immunocompromised host, including Kaposi's sarcoma, multicentric Castleman
      disease and primary effusion lymphoma. Acquisition and control of human
      herpesvirus 8 infection have not yet been fully elucidated. This review focuses
      on the most recent findings on human herpesvirus 8 transmission. RECENT FINDINGS:
      Horizontal transmission by saliva appears the most common route not only in
      families in endemic regions, but also among high-risk groups in Western
      countries. Vertical, sexual, and blood and transplant-related transmission,
      however, remain of significant concern worldwide. Novel approaches to standardize
      and optimize the assessment of human herpesvirus 8 infection have been reported.
      New insights on the host immune cell mechanisms devoted to the control of human
      herpesvirus 8 infection have also been presented. SUMMARY: The increasing
      knowledge about the routes of human herpesvirus 8 transmission, which appear now
      more similar to those of other more ubiquitous human herpesviruses (i.e. Epstein
      Barr virus and cytomegalovirus), the growing efforts in improving laboratory
      diagnosis and the caution in the research of new biological associations are the
      major recent findings. They constitute a fundamental background for directing
      more appropriate future research and achieving more stringent evidence useful for
      the control of human herpesvirus 8 spread and for the management of human
      herpesvirus 8-related diseases.

PMID- 17496574
TI  - Molecular diagnostic methods in pneumonia.
AB  - PURPOSE OF REVIEW: Molecular techniques offer the promise of improving diagnosis
      of lower respiratory tract infections. This review focuses on currently used
      molecular diagnostic techniques for various types of pneumonia and highlights
      potential future applications of this technology. RECENT FINDINGS: Lower
      respiratory tract infections result in a high degree of morbidity and mortality,
      but a definitive microbiologic diagnosis is often not obtained by traditional
      culture or serologic methods. In addition, culture of certain organisms may be
      difficult or require extended periods of time. Molecular techniques have the
      potential to improve diagnostic yield and decrease time to pathogen
      identification. These techniques are also helpful in the determination of drug
      sensitivity and the understanding of transmission and outbreaks. Most currently
      used techniques employ some variation of the polymerase chain reaction.
      Limitations include high costs, the need for specialized equipment, and problems
      with false-positive and -negative results. SUMMARY: Molecular diagnosis of
      pneumonia has the potential to improve identification of pathogens in patients
      with suspected lower respiratory tract infection. Limitations of molecular
      techniques currently prevent their widespread use, but future developments will
      likely lead to inclusion of these tests in routine diagnostic evaluations.

PMID- 17496575
TI  - Prognostic scoring systems: which one is best?
AB  - PURPOSE OF REVIEW: In the initial evaluation of patients with community-acquired
      pneumonia, a number of important assessments are made, including that of the
      severity of the illness. This assessment will determine the appropriate site of
      care, diagnostic work-up, and choice of empiric antibiotics. A number of severity
      assessment tools have been developed and some of the recent findings are
      reviewed. RECENT FINDINGS: A number of studies of the efficacy of the individual
      scoring systems, as well as comparator studies, have been undertaken. A
      significant number of patients with community-acquired pneumonia in Pneumonia
      Severity Index classes I and II are admitted to hospital and several of these
      patients suffer complications. Clinical and social factors other than those
      contained in the scoring systems need to be taken into consideration when
      deciding about hospitalization of patients with community-acquired pneumonia. A
      number of studies of the efficacy of the various scoring systems in predicting
      'severe pneumonia' have been undertaken, as well as studies of their accuracy in
      the sub-set of patients with pneumococcal infections and in the elderly. SUMMARY:
      The various scoring systems have reasonable sensitivity and specificity and their
      own strengths and weaknesses, but should always be used in association with good
      clinical judgment.

PMID- 17496576
TI  - New guidelines for the management of adult community-acquired pneumonia.
AB  - PURPOSE OF REVIEW: Community-acquired pneumonia is a major cause of morbidity and
      mortality, and is the leading cause of death from an infectious disease.
      International societies have published and revised guidelines aiming to improve
      the management of adult community-acquired pneumonia, based on the best available
      evidence. The aim of this review is to compare the current guideline
      recommendations. RECENT FINDINGS: Aspects of guidelines differ based on local
      factors including resources and antimicrobial factors, as well as the differences
      in interpretation of existing evidence. SUMMARY: The lack of robust evidence
      behind aspects of guideline recommendations as well as the lack of adherence to
      published guidelines both need to be addressed if the management of community
      acquired pneumonia is to be improved.

PMID- 17496577
TI  - How long should we treat community-acquired pneumonia?
AB  - PURPOSE OF REVIEW: The studies reviewed in this article suggest that a shorter
      duration of antibiotic therapy is comparable to standard therapy in the treatment
      of community-acquired pneumonia and promotes reduction of adverse events,
      microbial resistance, cost, and improved patient compliance. RECENT FINDINGS:
      Community-acquired pneumonia has traditionally been treated with a 7-14-day
      course of antimicrobial therapy. Since there have been few well controlled trials
      regarding the optimal duration of therapy, however, there has been no consensus
      on length of therapy among different organizational guidelines. Several recent
      studies have demonstrated that shorter course antibiotic regimens are effective
      in the treatment of community-acquired pneumonia. SUMMARY: Short-course
      antibiotic therapy is equivalent to standard length of therapy for clinical cure
      and bacterial eradication. Minimization of drug exposure, however, reduces
      selection pressure for resistant strains, strengthens patient compliance, and
      potentially reduces adverse events such as Clostridium difficile infections.

PMID- 17496578
TI  - Performance measures for pneumonia: are they valuable, and are process measures
      adequate?
AB  - PURPOSE OF REVIEW: Pneumonia has been the target of large national initiatives to
      measure and report quality of care. Measures of pneumonia care are now being used
      for public reporting and pay-for-performance in an effort to increase provider
      accountability for healthcare quality in the USA. Increasingly, concerns have
      been raised about the potential for unintended consequences of performance
      measurement and reporting that might lead to patient harm. RECENT FINDINGS: Since
      1999, there have been substantial improvements in performance on measures of
      pneumonia processes of care, and patient clinical outcomes have improved. The
      association between improved clinical outcomes and processes of care for
      pneumonia, however, is not clear based on available national data. The increasing
      use of process measures for hospital accountability has created the continual
      need to re-evaluate the relationship between processes being measured and desired
      patient outcomes. While there is little direct evidence of unintended
      consequences of performance measurement, concerns have been raised about the
      potential for direct or indirect harm to patients. SUMMARY: Measuring processes
      of care for pneumonia is feasible and appears to have accelerated the pace of
      quality improvement. There is an ongoing need to develop new measures of
      pneumonia quality that focus on patient outcomes, care transitions, and
      efficiency of care.

PMID- 17496579
TI  - Prevention measures for ventilator-associated pneumonia: a new focus on the
      endotracheal tube.
AB  - PURPOSE OF REVIEW: The aim of this article is to analyze the aspects related to
      the endotracheal tube which may influence the development of ventilator
      associated pneumonia and to review the possible measures of prevention. RECENT
      FINDINGS: The endotracheal tube participates in the pathogenesis of ventilator
      associated pneumonia by the elimination of natural defense mechanisms, thereby
      allowing the entry of bacteria by the aspiration of subglottic secretions or the
      formation of biofilm on the endotracheal tube. The preventive measures of
      ventilator-associated pneumonia related to the endotracheal tube include these
      two mechanisms. It has been suggested that substitution of the endotracheal tube
      by early tracheostomy may reduce the risk of ventilator-associated pneumonia.
      SUMMARY: Aspiration of the subglottic secretions seems to be an effective measure
      with little risk; decontamination or exhaustive control of the sealing of the
      cuff has not demonstrated a positive risk/benefit balance. The causal
      relationship between biofilm and ventilator-associated pneumonia has not been
      clearly established. Treatment of the biofilm with antibiotics, changes in the
      composition of the endotracheal tube or mechanical cleansing have achieved a
      reduction or elimination of the biofilm but their effect on the incidence of
      ventilator-associated pneumonia has not been studied. The benefit of early
      tracheostomy in reducing ventilator-associated pneumonia is still controversial.

PMID- 17496580
TI  - Therapy of nontuberculous mycobacterial disease.
AB  - PURPOSE OF REVIEW: Nontuberculous mycobacterial disease, especially pulmonary
      disease, is increasingly encountered by clinicians. Therapy of the most common
      nontuberculous mycobacterial pathogen, Mycobacterium avium complex, improved with
      the introduction of macrolide-containing regimens, but treatment for this and
      most other nontuberculous mycobacterial pathogens remains difficult. RECENT
      FINDINGS: Treatment trials with macrolide-containing regimens for Mycobacterium
      avium complex lung disease have yielded generally favorable outcomes. Studies
      consistently show that in-vitro susceptibility to macrolides remains the only in
      vitro susceptibility for Mycobacterium avium complex that correlates with in-vivo
      response. Patients who have macrolide-resistant Mycobacterium avium complex
      isolates are much harder to treat and have higher mortality than patients with
      macrolide-susceptible isolates. Studies also consistently show that patients who
      fail therapy, even those who remain macrolide susceptible in vitro, are more
      difficult to treat than patients without previous therapy. SUMMARY: There have
      been no significant treatment advances for Mycobacterium avium complex lung
      disease, and nontuberculous mycobacterial disease in general, since the advent of
      the newer macrolides. It has become clear that the best opportunity for treatment
      success is the first treatment effort. It is also clear that protection against
      the emergence of macrolide-resistant Mycobacterium avium complex isolates is
      critically important. For further progress in the treatment of these pathogens,
      new and more active drugs must be developed.

PMID- 17496581
TI  - Current world literature. Skin and soft tissue infections.

PMID- 17496582
TI  - Congenital erythroleukemia presenting as a congenital infantile hemangioma.

PMID- 17496583
TI  - The surgical treatment of brachial plexus injuries in adults.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Evaluate clinically a patient with brachial plexus paralysis and define
      the appropriate electrophysiologic and radiographic studies. 2. Differentiate
      between preganglionic (root) avulsion and postganglionic lesions and identify
      appropriate motor donors and nerve grafts. 3. Describe various nerve
      reconstructive strategies and make appropriate selection of secondary procedures
      for shoulder stability, elbow flexion, and hand reanimation. 4. Anticipate the
      possible functional outcome.

PMID- 17496584
TI  - Functional capacity and postural pain outcomes after reduction mammaplasty.
AB  - BACKGROUND: Neck, shoulder, and lower back pain and reduction of functional
      capacity can be caused by breast hypertrophy. Reduction mammaplasty appears to
      improve these aspects. After a systematic review of the literature, no scientific
      evidence was found to confirm this hypothesis. The authors' objective was to
      evaluate the impact of reduction mammaplasty on pain and functional capacity of
      patients with mammary hypertrophy. METHODS: One hundred patients with mammary
      hypertrophy, between 18 and 55 years old, with no previous mammary surgery, were
      consecutively selected from the Plastic Surgery Outpatient Clinic of the
      Universidade Federal de Sao Paulo-Escola Paulista de Medicina and randomly
      allocated into two groups. Group A (n = 50) underwent mammaplasty reduction
      immediately, whereas group B patients (n = 50) were placed on a waiting list
      (control group). All patients were interviewed for clinical and demographic data
      and evaluated to measure pain and functional capacity. To measure shoulder, neck,
      and lower back pain, a visual analogue scale (0 = no pain, 10 = unbearable pain)
      was used. The Stanford Health Assessment Questionnaire (HAQ-20), Brazilian
      validated version (0 = best, 3 = worst), was applied to assess functional
      capacity. Pain and functional capacity were measured at baseline and 6 months
      after surgery. RESULTS: Forty-six of 50 patients, from both groups, completed the
      study. The mean (+/-SD) patient age in groups A and B was 31.6 +/- 11 and 32.3 +/
      10 years, respectively. The mean breast tissue weight was 1052 +/- 188 g.
      Functional capacity in group A was improved 6 months after reduction mammaplasty,
      compared with group B (control), in the following aspects: getting dressed,
      getting up, walking, maintaining personal hygiene, reaching, and grasping
      objects. The mean pain intensity dropped in the lower back, from 5.7 to 1.3; in
      the shoulders, from 6.1 to 1.1; and in the neck, from 5.2 to 0.9. CONCLUSION:
      Reduction mammaplasty improved functional capacity and relieved pain in the lower
      back, shoulders, and neck of patients with mammary hypertrophy.

PMID- 17496586
TI  - Completely autologous platelet gel in breast reduction surgery: a blinded,
      randomized, controlled trial.
AB  - BACKGROUND: The objective of this study was to assess the effectiveness of
      topical application of completely autologous platelet gel during breast surgery
      to reduce postoperative wound drainage. An increasing number of surgical centers
      are using tissue sealants to reduce postoperative drainage and improve surgical
      outcomes. However, there is a paucity of randomized, double-blind, controlled
      trials assessing the efficacy of these agents. METHODS: The authors conducted a
      within-patient, randomized, patient- and assessor-blinded, controlled trial
      assessing the use of completely autologous platelet gel in 111 patients
      undergoing bilateral reduction mammaplasty. Patients were randomized to receive
      the gel applied to the left or right breast after hemostasis was achieved; the
      other breast received no treatment. The primary outcome was the difference in
      wound drainage over 24 hours. Secondary outcomes included subjective and
      objective assessments of pain and wound healing. RESULTS: No statistically
      significant differences in the drainage, level of pain, size of open areas,
      clinical appearance, degree of scar pliability, or scar erythema were noted.
      CONCLUSION: The authors' results do not support the use of completely autologous
      platelet gel to improve outcomes after reduction mammaplasty.

PMID- 17496587
TI  - Vascular reliability of nipple-areola complex-bearing pedicles: an anatomical
      microdissection study.
AB  - BACKGROUND: Vascular-dependent necrosis of the nipple-areola complex following
      reduction mammaplasty is still present. Concerning anatomy, there is a lack of
      literature comparing the vasculature of different nipple-areola complex-bearing
      pedicles in detail. Including six arterial sources supplying the breast, this
      anatomical work intends to clarify arterial impact and vascular reliability of
      different nipple-areola complex-bearing pedicles. METHODS: Microdissections of
      anterior chest walls following vessel filling with dye were performed to examine
      the architecture of the arteries supplying the breast and their contribution to
      the blood supply of the nipple-areola complex on seven female corpses (14
      breasts). RESULTS: Four of six arterial sources supporting the breast were found
      to be mainly responsible for the blood supply of the nipple-areola complex. These
      are, in descending order of reproducibility, branches originating from the
      lateral thoracic artery, the internal mammary artery, the anterior branches of
      the intercostal arteries, and those deriving from the highest thoracic arteries.
      Despite vessel variability, both arrangements and subcutaneous courses of
      arteries advancing to the nipple-areola complex showed characteristic
      relationships. CONCLUSIONS: Vascular variability and overlap may account for the
      remarkable safety of diverse nipple-areola complex-bearing pedicles, even though
      pedicle thickness influences vascular reliability. Lateral and medial approaches,
      however, clearly show vascular advantages over that which can be observed in
      inferior and superior pedicles. The former may therefore be regarded as more
      reliable. Especially the full-thickness glandular dermal superolaterally based
      pedicle should regularly enclose dominant branches originating from the lateral
      thoracic artery and supplementary arteries deriving from minor important sources
      in this region.

PMID- 17496588
TI  - The endoscope as an adjunct to correction of nipple inversion deformity.
AB  - BACKGROUND: Correction of the inverted nipple requires release of constricting
      fibrous tissue and suspension of the nipple. Despite the simplicity, lasting
      repair is often difficult to achieve, as is the ability to assure preservation of
      functioning lactiferous ducts during release. METHODS: Since 2002, the authors
      have used the endoscope to guide selective division of retracted fibrous bands,
      followed by the use of a dermal fat graft and purse-string suture to the base to
      achieve stable nipple projection. RESULTS: In this series of 28 nipples of 15
      patients, the patients were followed up for a mean period of 14 months (range, 6
      to 26 months). The outcome was judged to be excellent in 23 nipples (82 percent)
      and fair in five (18 percent). There were no instances of any changes in
      sensitivity of the nipple-areola complex. Four patients experienced lactation
      afterward. CONCLUSIONS: The endoscope clearly delineated band from duct. The
      authors' technique was able to maintain excellent projection, with preservation
      of breast feeding as well as normal breast sensation, except in grade IIIB
      inverted nipples.

PMID- 17496589
TI  - Internal pedicle shaping to improve aesthetic results in reduction mammaplasty.

PMID- 17496590
TI  - Autologous lipofilling: coenzyme Q10 can rescue adipocytes from stress-induced
      apoptotic death.
AB  - BACKGROUND: Autologous fat transplantation (or lipofilling) is an excellent
      technique for correction of cosmetic defects. The success of the procedure relies
      strongly on the techniques of harvesting and transferring viable adipocytes. The
      purpose of this study was to evaluate effects of two harvesting methods and
      coenzyme Q10 on the viability and apoptotic death of adipocytes collected for
      autologous lipofilling. METHODS: Human adipose tissue from six patients was
      collected by Luer-Lok syringe according to Coleman's technique or by means of an
      aspirator with a 680-mmHg vacuum. Half of each sample collected using Coleman's
      technique was treated with 10 muM Coenzyme Q10, and the other half served as
      untreated control. Viability and apoptosis were assessed by immunoenzymatic,
      biochemical, and morphological methods. RESULTS: The harvesting of adipose tissue
      by aspirator reduced the viability and increased apoptotic death significantly
      more than harvesting tissue using Coleman's technique. Biochemical and
      morphological analyses confirmed that treatment of adipose tissue with coenzyme
      Q10 reduced and even inhibited apoptotic death of harvested adipocytes.
      CONCLUSION: Coenzyme Q10 can rescue adipocytes from stress-induced apoptotic
      death.

PMID- 17496591
TI  - Anti-TGF-beta2 antibody therapy inhibits postoperative resynostosis in
      craniosynostotic rabbits.
AB  - BACKGROUND: Postoperative resynostosis is a common clinical finding. It has been
      suggested that an overexpression of transforming growth factor (TGF)-beta2 may be
      related to craniosynostosis and may contribute to postoperative resynostosis.
      Interference with TGF-beta2 function with the use of neutralizing antibodies may
      inhibit resynostosis. The present study was designed to test this hypothesis.
      METHODS: New Zealand White rabbits with bilateral coronal suture synostosis were
      used as suturectomy controls (group 1, n = 9) or given suturectomy with
      nonspecific, control immunoglobulin G antibody (group 2, n = 9) or suturectomy
      with anti-TGF-beta2 antibody (group 3, n = 11). 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 0.1 cc of a slowly resorbing collagen gel mixed with either
      immunoglobulin G (100 mug per suture) or anti-TGF-beta2 (100 mug per suture).
      Three-dimensional computed tomography scan reconstructions of the defects were
      obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for
      histomorphometric analysis. RESULTS: Computed tomography scan data revealed that
      the suturectomy sites treated with anti-TGF-beta2 showed significantly (p < 0.05)
      greater areas through 84 days of age compared with controls. Histomorphometry
      also showed that suturectomy sites treated with anti-TGF-beta2 had patent
      suturectomy sites and more fibrous tissue in the defects compared with sites in
      control rabbits and had significantly (p < 0.001) less new bone area (by
      approximately 215 percent) in the suturectomy site. CONCLUSIONS: These data
      support the initial hypothesis that interference with TGF-beta2 function
      inhibited postoperative resynostosis in this rabbit model. They also suggest that
      this biologically based therapy may be a potential surgical adjunct to retard
      postoperative resynostosis in infants with craniosynostosis.

PMID- 17496593
TI  - Comparison of guided bone formation from periosteum and muscle fascia.
AB  - BACKGROUND: Muscle fascia and periosteum have been used clinically to guide
      prefabrication of vascularized bone flaps for reconstruction of complex three
      dimensional tissues. Although it seems that both locations have the capacity to
      generate vascularized bone, there have been no studies that directly compare
      different implantation sites. The authors performed a rigorous, quantitative,
      histomorphometric comparison of bone prefabrication in a large-animal model
      comparing graft implanted against muscle fascia and periosteum. METHODS: Twenty
      skeletally mature domestic sheep were implanted with rectangular chambers
      containing equal weights of morcellized bone graft. Two chambers were implanted
      into each sheep, one with the open face apposed to the cambium layer of the rib
      periosteum and the other with the open face apposed to the fascia of the
      latissimus dorsi muscle. Animals were euthanized at 3, 6, 9, 12, and 24 weeks and
      the chambers were harvested. Tissue inside the chambers was analyzed for shape
      conformation to chamber geometry, gross tissue volume, and bone histomorphology.
      RESULTS: There were no differences in volume or shape of tissue formed in the
      chambers. However, chambers in contact with fascia consisted almost entirely of
      fibrovascular tissue, with progressive resorption of the morcellized bone graft
      and little evidence of new bone. Chambers in contact with periosteum showed
      active endochondral, direct, and appositional bone formation over time, with
      increasing calcified tissue area and new bone formation. CONCLUSIONS: Both
      periosteum and muscle fascia were able to vascularize bone grafts, but bone
      formation was higher in the periosteum. The periosteum appears to be a more
      suitable foundation from which to promote flap prefabrication.

PMID- 17496594
TI  - Analysis of salvage treatments following the failure of free flap transfer caused
      by vascular thrombosis in reconstruction for head and neck cancer.
AB  - BACKGROUND: Few authors have reported the subsequent treatment for patients in
      whom free tissue transfers in the head and neck have failed as a result of
      vascular thrombosis. METHODS: Between 1993 and May of 2005, 502 free flaps were
      transferred after head and neck cancer ablation in the authors' hospital, 19 of
      which resulted in total necrosis caused by vascular thrombosis. The authors
      categorized these 19 cases into four groups and analyzed the salvage treatment.
      RESULTS: For failed free jejunal transfer, early initiation of oral intake was
      obtained when another free jejunum was transferred. For failed free soft-tissue
      transfer for intraoral defects, reconstruction with common free (first choice) or
      pedicled flaps was used: a voluminous musculocutaneous flap for extensive
      defects, forearm flap or pedicled pectoralis major flap for intermediate defects,
      and direct closure for small defects of the oral floor. For failed secondary soft
      tissue transfer to improve a certain function, salvage flap transfer was not
      chosen in the acute setting. For failed secondary maxillary reconstruction,
      simple reconstruction using the rectus abdominis musculocutaneous flap combined
      with costal cartilage achieved stable results. The overall success rate of the
      repeated free flap was 89 percent (eight of nine patients). CONCLUSIONS: When a
      free flap is judged unsalvageable, surgeons should determine subsequent
      treatments, considering the success rate as one of the most important factors.
      The authors believe that simple reconstruction using a common free flap is the
      first choice in most cases. When regional or general conditions do not permit
      further free flap transfer or when defects are comparatively small,
      reconstruction with a pedicled flap or direct closure of the defect may be
      considered.

PMID- 17496595
TI  - Outcomes of periocular reconstruction for facial nerve paralysis in cancer
      patients.
AB  - BACKGROUND: Facial nerve paralysis is a common event in patients with head and
      neck cancer or metastasis of cancer to the parotid region. The aim of this study
      was to evaluate the outcomes of periocular reconstruction for facial nerve
      paralysis in cancer patients. METHODS: The medical records of all patients who
      had undergone periocular surgery for facial nerve paralysis between January of
      1999 and December of 2003 were retrospectively reviewed. The outcome measures
      included the ocular symptoms and signs, improvement in symptoms of exposure
      keratopathy postoperatively, timing of periocular surgery in relation to
      radiotherapy, and surgical complications. RESULTS: Preoperative symptoms included
      burning sensation (25 of 78 patients), difficulty with vision (30 of 78),
      frequent use of lubricating drops and ointments (52 of 78), and excessive tearing
      (37 of 78). The degree of lagophthalmos ranged from 1.5 to 12 mm (mean, 6.5 mm)
      preoperatively and from 0 to 4.5 mm (mean, 1.5 mm) postoperatively. Seventy-eight
      patients had gold weight placement; 72 of them also had lateral tarsorrhaphy, 56
      had lower eyelid tightening via a lateral tarsal strip procedure in addition to
      the gold weight and lateral tarsorrhaphy, and 22 had brow elevation in addition
      to all the above-mentioned procedures. Four also required a medial tarsorrhaphy.
      All patients reported less dependence on lubricating drops and ointments after
      periocular surgery. Eighteen of 25 patients who had foreign body sensation as
      their main preoperative symptom experienced improvement after surgery. Forty-four
      patients had radiotherapy to the head and neck region. Twenty-seven patients
      completed radiotherapy before and 17 after periocular reconstruction.
      Complication rates were low and comparable in both preoperative and postoperative
      radiation groups. CONCLUSIONS: Periocular reconstruction for facial paralysis
      results in improvement of exposure keratopathy and less dependence on lubricating
      drops and ointments. Complications are minimal and infrequent. The timing of
      external beam radiotherapy does not affect the outcomes of periocular surgery.

PMID- 17496596
TI  - Comparison of acellular dermal matrix and synthetic mesh for lateral chest wall
      reconstruction in a rabbit model.
AB  - BACKGROUND: Synthetic mesh is used for chest wall reconstruction, but infection
      or exposure can occur and necessitate removal. Human acellular dermal matrix
      (AlloDerm) has been used to reconstruct musculofascial defects in the trunk with
      low infection and herniation rates. AlloDerm may have advantages over synthetic
      mesh for chest wall reconstruction. This study compared outcomes and repair
      strengths of AlloDerm to expanded polytetrafluoroethylene mesh used for repair of
      rib cage defects. METHODS: A 3 x 3-cm, full-thickness, lateral rib cage defect
      was created in each rabbit and repaired with expanded polytetrafluoroethylene (n
      = 8) or acellular dermal matrix (n = 9). At 4 weeks, the animals were euthanized
      and evaluated for lung herniation/dehiscence, strength of adhesions between the
      implant and intrapleural structures, and breaking strength of the implant
      materials and the implant-fascia interface. Tissue sections were analyzed with
      histologic and immunohistochemical staining to evaluate cellular infiltration and
      vascularization. RESULTS: No herniation or dehiscence occurred with either
      material. The incidence and strength of adhesions was similar between materials.
      The mean breaking strength of the AlloDerm-fascia interface (14.5 +/- 8.9 N) was
      greater than the expanded polytetrafluoroethylene-fascia interface (8.7 +/- 4.4
      N; p = 0.027) and similar to the rib-intercostal-rib interface of the
      contralateral native chest wall (14.0 +/- 5.6 N). The AlloDerm grafts became
      infiltrated with cells and vascularized after implantation. CONCLUSIONS: AlloDerm
      used for chest wall reconstruction results in greater implant-defect interface
      strength than expanded polytetrafluoroethylene. The ability of AlloDerm to become
      vascularized and remodeled by autologous cells and to resist infection may be
      advantageous for chest wall reconstruction.

PMID- 17496599
TI  - The perforator-sparing buttock rotation flap for coverage of pressure sores.
AB  - BACKGROUND: The rotation fasciocutaneous flap for buttock pressure sore coverage
      has the distinct advantage of allowing rerotation in the event of ulcer
      recurrence. The authors describe their approach of preserving and incorporating
      musculocutaneous perforators into the conventional rotation design. METHODS: The
      skin incision is the same as that for the conventional gluteal rotation flap. The
      flap is elevated subfascially until one or two large musculocutaneous perforators
      of the superior or inferior gluteal arteries are encountered. Intramuscular
      dissection by splitting fibers of the gluteus maximus muscle is then performed to
      free the perforator down to its emergent point at the level of the piriformis
      muscle to enable the perforator to pivot freely with the rotation of the skin
      flap. Further elevation of the flap beyond the location of the perforator is then
      performed as necessary to enable tension-free rotation of the skin flap into the
      defect. Muscle to fill dead space when needed is raised as a separate flap. Seven
      patients underwent closure of buttock pressure sores in the sacral, ischial, and
      trochanteric areas using this technique. RESULTS: All wounds healed, with no
      recurrence, at a mean follow-up of 30 months. This technique can be used to cover
      pressure sores over the sacral, trochanteric, and ischial regions. CONCLUSIONS:
      This modification of the conventional rotation flap affords the flexibility of
      rerotation in the event of ulcer recurrence while providing the flap with
      enhanced blood supply. This is an ideal flap for patients in whom the risk of
      ulcer recurrence is high.

PMID- 17496597
TI  - Incidence and management of abdominal wall defects after intestinal and
      multivisceral transplantation.
AB  - BACKGROUND: Successful primary closure of the abdominal wall following visceral
      organ transplantation is not always feasible. Primary closure under tension can
      lead to fascial ischemia or necrosis, with subsequent dehiscence. Thus, alternate
      techniques to achieve abdominal wall closure are an important technical aspect in
      intestinal transplantation. The authors review their experience managing
      abdominal wall defects following intestinal or multivisceral transplantation.
      METHODS: A retrospective review of the transplant database revealed 28 intestinal
      transplants in 24 patients from program inception in 1991 to January of 2002. The
      management of six intestinal transplant recipients with giant posttransplant
      abdominal wall defects is reviewed, and a novel technique is described for
      initially managing defects with prosthetic grafts that were serially reduced in
      size until a clean granulating bed was established, at which time they underwent
      permanent coverage using a meshed split-thickness skin graft. RESULTS: Of the 28
      transplants, primary fascial closure was possible in only 14. In the other 14
      patients, the fascia could not be closed primarily at the time of
      transplantation. The donor weight-to-recipient weight ratio was significantly
      greater in patients with abdominal wall closure problems (0.64 versus 1.09; p <
      0.005). The incidence of retransplantation was also higher in those with
      abdominal closure problems compared with those whose fascia could be closed
      primarily (five of 14 versus one of 14). The six patients managed with skin graft
      closure did not have any wound complications after grafting. CONCLUSIONS:
      Abdominal wall defect after intestinal and multivisceral transplantation is a
      common problem without an ideal solution. Use of a skin graft on granulating
      abdominal viscera frozen with adhesions is a simple and reasonable solution to a
      complex problem.

PMID- 17496600
TI  - Introduction of microsurgery in Vietnam by a charitable organization: a 15-year
      experience.
AB  - BACKGROUND: Microsurgical procedures, although equipment- and labor-intensive,
      allow efficient treatment of selected soft-tissue, bone, and peripheral nerve
      defects. The precise surgical skills required and the high equipment and
      institutional costs have been deterrents to initiating programs in developing
      countries. The authors report their 15-year international effort in facilitating
      the development of microsurgical techniques in Vietnam. METHODS: The authors
      reviewed their educational, logistical, and operative experience from 11
      Operation Smile International missions to Vietnam and the microsurgical
      procedures performed independently by Vietnamese surgeons at the Central Military
      Hospital 108 in Hanoi. RESULTS: Over 15 years, Operation Smile International
      missions to Vietnam performed 108 free tissue transfer operations with 15
      peripheral nerve transfer procedures and 143 nonmicrosurgical reconstructive
      operations. Visiting surgeons with specialized expertise taught facial
      reanimation, flap prefabrication, and perforator flaps. During this same period,
      Vietnamese surgeons became facile with microsurgical techniques and independently
      performed a wide array of these procedures in the institutions visited.
      Vietnamese surgeons have organized microsurgery divisions within some hospital
      departments and now teach microsurgical techniques. Repeated missions allowed for
      patient follow-up, staged procedures, educational exchange, and quality control.
      Several Vietnamese surgeons have traveled abroad to obtain additional training
      and have set up training programs in other areas of Vietnam. CONCLUSIONS:
      Charitable organizations can help surgeons in developing countries master complex
      microsurgical techniques through short-term medical missions, donation of
      equipment and supplies, and the encouragement of institutional support. A
      continuing education program, including local conferences, microsurgical
      laboratory training facilities, and study abroad, can aid this introduction.

PMID- 17496603
TI  - The place of chemical leeching with heparin in digital replantation: subcutaneous
      calcium heparin for patients not treatable with systemic heparin.
AB  - BACKGROUND: In patients with replanted digits, systemic heparinization or other
      techniques may be used for prevention of thrombosis of the vascular anastomoses
      or to prevent coagulation at the drainage site (e.g., a fish-mouth incision or
      partially removed nail). However, systemic heparin may be contraindicated or
      require cautious administration in certain patients. The authors injected calcium
      heparin subcutaneously into the congested replanted digits of seven patients with
      a history of or undergoing treatment for hemorrhoids or gastric ulcer and drained
      the congestion by means of a fish-mouth incision. METHODS: With this method, 0.8
      ml (20,000 U) of calcium heparin for subcutaneous injection was diluted with 1.2
      ml of saline to prepare a solution containing 1000 U in 0.1 ml; this calcium
      heparin solution (1000 U) was initially injected into the tip of the congested
      digit. If required, additional doses of 500 U each were administered every 24
      hours until the congestion improved. RESULTS: No worsening of bleeding from
      hemorrhoids or gastric ulcer was seen after the administration of calcium heparin
      in these patients. Regarding duration of action, continuous bleeding for
      approximately 6 hours was obtained after subcutaneous injection of 1000 U, and
      thereafter, adequate drainage was achieved for approximately 24 hours by
      stimulating the drainage site. CONCLUSIONS: Among patients in whom systemic
      heparin is contraindicated or who require cautious administration, this is a very
      effective technique in those in whom congestion fails to improve despite
      thrombectomy, patients in whom thrombectomy or vascular reanastomosis is not
      possible, and patients with congestion caused by narrow anastomosed veins.

PMID- 17496602
TI  - Use of quantitative abductor pollicis brevis strength testing in patients with
      carpal tunnel syndrome.
AB  - BACKGROUND: Diagnosis of carpal tunnel syndrome remains clinical, despite many
      objective clinical and electrophysiologic tests. There is also a need to
      objectively assess the severity of involvement and the need for surgery, and to
      document response to treatment. The authors evaluated a hand-held strength
      testing device for assessment of abductor pollicis brevis strength in patients
      with carpal tunnel syndrome. METHODS: Sixty-two hands in 50 patients (39 women
      and 11 men) aged 26 to 57 years were examined. All hands were evaluated before
      and 6 weeks after surgery. Nineteen hands were available for 7-year follow-up.
      RESULTS: Abductor pollicis brevis strength following carpal tunnel release
      increased significantly from a mean of 2.3 kg to 3.1 kg. The strength further
      increased in all long-term follow-up patients. CONCLUSIONS: Quantitative strength
      testing can be used to document changes in abductor pollicis brevis strength in
      response to treatment in patients with carpal tunnel syndrome. Further study is
      needed to assess the reliability of this testing method using multiple examiners
      in patients with carpal tunnel syndrome, and to evaluate the utility of using
      this device in tracking the long-term outcome of patients after carpal tunnel
      release.

PMID- 17496604
TI  - Preoperative osseous dysmorphology in unilateral complete cleft lip and palate: a
      quantitative analysis of computed tomography data.
AB  - BACKGROUND: The purpose of this study was to quantitate preoperative osseous
      dysmorphology in a homogeneous group of 3-month-old infants with unilateral
      complete cleft lip and palate. METHODS: High-resolution computed tomography scans
      of 28 infants with unilateral complete cleft lip and palate were the basis for
      study. Coordinate data from 43 landmarks on the skull were collected using
      surface-rendered reconstructions of scan data. Euclidean distance matrix analysis
      was used to assess the degree of asymmetry between the cleft and noncleft sides
      of the craniofacial skeleton. RESULTS: Linear distances involving primary and
      secondary landmarks (those that are located on or within the bony cleft and those
      that are near the cleft in the adjacent oronasal area, respectively) were highly
      asymmetric, with significantly greater distances on the cleft side. In addition,
      small (1 to 5 percent) but statistically significant asymmetries in linear
      distances were found involving tertiary landmarks (those that are not directly
      associated with the cleft or adjacent oronasal area). Most linear distances
      involving the nasion, zygomaxillare superius, and frontozygomatic junction were
      significantly greater on the cleft side, and certain linear distances in and
      around the middle cranial fossa were significantly smaller on the cleft side.
      CONCLUSIONS: The extreme asymmetry of primary and secondary landmarks is
      explained by the cleft itself and the obvious displacement of the premaxilla
      toward the noncleft side. The subtler, statistically significant asymmetry of the
      tertiary landmarks supports the idea that the unilateral cleft affects
      development of the entire face and possibly the cranial base. Euclidean distance
      matrix analysis of computed tomography landmark data is a useful methodology for
      the quantitative morphometry of children with untreated unilateral cleft lip and
      palate.

PMID- 17496605
TI  - Delayed closure of the hard palate leads to speech problems and deleterious
      maxillary growth.
AB  - BACKGROUND: Hard palate cleft closure has been associated with maxillary
      hypoplasia. The Schweckendiek procedure offers delayed hard palate closure to
      avoid early subperiosteal dissection and palatal scarring. This study sought to
      compare single-stage versus delayed hard palate closure for speech outcome and
      maxillary growth. METHODS: A retrospective outcome study was performed of
      unilateral cleft lip and palate patients with either delayed hard palate repair
      with a pinned-retained speech prosthesis (Schweckendiek repair) (group 1, delayed
      hard palate repair, 1978 to 1983) or single-stage cleft palate repair (group 2,
      single-stage repair, 1983 to 1988). Patients with complete records to maturity at
      the University of Pittsburgh Cleft Palate Craniofacial Center (n = 82, two equal
      groups of 41 patients) were studied. Comparative data were collected from
      multidisciplinary evaluations, perceptual speech scores, speech tests, and
      cephalometric analysis. RESULTS: Single-stage cleft palate repair had a lower
      fistulization rate (11 percent) compared with delayed hard palate repair (58
      percent). It also had better speech outcomes compared with delayed hard palate
      repair: mean speech score, 3.1 versus 7.8; final speech score, 0.9 versus 2.9;
      velopharyngeal incompetency, 21 percent versus 66 percent; failed video
      fluoroscopy or nasoendoscopy, 18 percent versus 52 percent; and need for
      secondary speech procedure, 20 percent versus 63 percent. Single-stage repair
      showed less maxillary growth disturbance, with class III malocclusion, 31 percent
      versus 66 percent; cephalometric SNA, 78.2 versus 74.8; need for Le Fort I
      advancement, 24 percent versus 42 percent; and amount of maxillary advancement
      required, 6 mm versus 9 mm. CONCLUSION: The delayed cleft palate repair led to
      worse speech outcomes; thus, the authors' center abandoned this technique in
      favor of single-stage repair. In addition, their data showed that the delayed
      cleft palate repair led to deleterious maxillary growth.

PMID- 17496606
TI  - Surgical management of posttraumatic temporomandibular joint ankylosis by
      functional restoration with disk repositioning in children.
AB  - BACKGROUND: Management of temporomandibular joint ankylosis poses a challenge
      because of technical difficulties and recurrence. The problem is more troublesome
      in children because of the involvement of postoperative development of the
      mandible. During the process of management of temporomandibular joint ankylosis,
      in many cases, the authors observed that the disk may exist outside of the bone
      mass in posttraumatic ankylosis. On the basis of this fact, the authors' working
      hypothesis was that if the disk could be retained and repositioned, with limited
      resection of the residual stump of the ramus to maintain its height, the
      structure and function of temporomandibular joint could be restored to a maximum
      degree to provide normal function and growth in children. METHODS: Ten children
      with temporomandibular joint ankylosis underwent this approach, in which the disk
      was retained and repositioned and the residual stump of the ascending ramus was
      preserved and reshaped to maintain its height. All patients were reviewed
      regularly and evaluated retrospectively. RESULTS: The follow-up period ranged
      from 17 to 52 months (average, 32.9 months). All patients had significant
      improvement in mouth opening and showed a distinctive improvement both in
      articular functionality and in symptoms. No relapse occurred and no secondary
      deformity in the mandible resulted. CONCLUSIONS: The approach described not only
      helps to prevent relapse of temporomandibular joint ankylosis but also takes
      postoperative mandible development into consideration. The authors deem that it
      is a good choice for surgical management of posttraumatic temporomandibular joint
      ankylosis in children.

PMID- 17496607
TI  - Increased intraabdominal pressure in abdominoplasty: delineation of risk factors.
AB  - BACKGROUND: Abdominoplasty is associated with a 1.1 percent risk of deep venous
      thrombosis. This has been attributed to rectus plication causing intraabdominal
      hypertension, known to effect decreased venous return, venous stasis, and thus
      thrombosis. The authors conducted a pilot study to determine which components of
      the abdominoplasty procedure (i.e., general anesthesia, flexion of the bed,
      plication, and/or binder placement) may elevate intraabdominal pressures and
      whether this was clinically relevant. METHODS: Twelve abdominoplasty and 10
      breast reduction (control) patients were enrolled prospectively. Intraabdominal
      pressure was transduced through the bladder before plication in the supine and
      flexed positions, after plication in both positions, after skin closure in the
      flexed position, and on postoperative day 1 with and without a binder in the
      flexed position. RESULTS: All intraabdominal pressures measured were clinically
      insignificant (<20 mm Hg). A statistically significant increase was found from
      flexion of the bed (mean difference, 3.80 +/- 2.0, p < 0.001, in the control
      group; and 4.39 +/- 1.68, p < 0.001, in the study group); rectus plication (mean
      difference, 2.78 +/- 2.11, p = 0.001, in the supine position; and 2.03 +/- 2.48,
      p = 0.016, in the flexed position); and binder placement (2.63 mm Hg for no
      binder versus 4.5 mm Hg with binder, p = 0.004). Both groups also showed an
      increase from preoperative to skin closure (mean difference, 2.03 +/- 6.7, p =
      0.035, for the control group; and 2.83 +/- 3.97, p = 0.031, for the study group),
      suggesting general anesthesia as a risk factor. CONCLUSIONS: This study confirms
      the effect of rectus plication on increasing intraabdominal pressures but also
      implicates bed position, binder placement, and general anesthetic as risk
      factors. A larger study is needed to clarify the role of these variables in
      elevating intraabdominal pressure during abdominoplasty.

PMID- 17496608
TI  - The use of polyacrylamide gel in soft-tissue augmentation: an experimental
      assessment.
AB  - BACKGROUND: An increasing number of soft-tissue filler substances that lack
      experimental and clinical data have been introduced into plastic surgery practice
      outside the United States. One of these substances is polyacrylamide gel. It
      contains 2.5% polyacrylamide and 97.5% water. It is homogenous and stable, and
      has optimum viscosity and elasticity. METHODS: One milliliter of polyacrylamide
      gel was injected into the subcutaneous layer of the right ear in 28 rabbits. The
      rabbits were divided into two groups, according to when the material was
      harvested and evaluated. Material was harvested at 4 months in 15 rabbits and 7
      months in 13 rabbits. Each group underwent volumetric ultrasound evaluation,
      magnetic resonance imaging, and histological evaluation with hematoxylin and
      eosin and CD68 staining. RESULTS: Results were easily observed because of the
      superficial position of the injected material. There were no systemic or local
      complications. The samples harvested showed a clear and jelly-like consistency
      similar to that of the initially injected material. The volume was constant after
      6 weeks, after an initial period of acute stretching. Ultrasound volumetric
      analysis was also constant in all groups. At 7 months, a stable volume of 1.0 +/-
      0.2 ml was observed. Magnetic resonance imaging scanning showed that the material
      was stable and that there was no inflammatory reaction. Histological analysis
      revealed a minimal foreign-body reaction, and the injected material was
      occasionally surrounded by a thin collagen membrane. The material remained in
      place. CONCLUSIONS: Polyacrylamide gel has a long-lasting effect, with minimal
      volume variation. It remains soft to the touch and in place.

PMID- 17496609
TI  - Classification of brachial ptosis: strategy for treatment.
AB  - BACKGROUND: The author presents a clinical classification of brachial ptosis
      based on the amount of adipose tissue deposit and the degree of ptosis. This
      system offers guidelines for graduated treatment of fat deposit and brachial
      ptosis. Minor modifications to previous techniques are reported to keep the scar
      short, as low as possible, and not wide, and to avoid postoperative contour
      deformities. Five groups of upper arm problems are described, as follows: stage
      1, patients with minimal fat deposit and no ptosis; stage 2a, patients with
      moderate fat deposit and grade 1 ptosis; stage 2b, patients with severe fat
      deposit and grade 2 ptosis; stage 3, patients with severe fat deposit and grade 3
      ptosis; and stage 4, patients with minimal or no fat deposit and with grade 3
      ptosis. METHODS: Between 1996 and 2005, four modalities were used to treat 60
      patients with brachial deformities: single-stage liposuction, staged liposuction,
      suction-assisted short scar brachioplasty, and conventional brachioplasty. Age at
      operation ranged between 24 and 56 years. All patients were seen and the author
      reviewed their medical charts during the follow-up period (12 to 38 months).
      RESULTS: All patients who underwent liposuction-assisted arm dermolipectomy
      (stages 2a and 3) were free of incorrectly placed incisions and postoperative
      contour deformities. Postoperatively, skin laxity and ptosis in the axillary
      regions were encountered in two stage 4 patients. One patient experienced widened
      and hypertrophied scar secondary to wound infection. One stage 3 patient and one
      stage 4 patient developed postoperative distal edema. CONCLUSION: The clinical
      classification and treatment guidelines reported are designed to provide simple
      procedures with minimal complications that tremendously rejuvenate the arm.

PMID- 17496610
TI  - Realistic expectations: to morph or not to morph?
AB  - BACKGROUND: The purpose of this study was to determine whether computer-morphed
      images convey realistic expectations of the postoperative cosmetic result to
      patients seeking rhinoplasty. METHODS: This was a retrospective study in which
      preoperative, computer-morphed, and 1-year postoperative images of 25 consecutive
      rhinoplasty patients were analyzed by 12 anonymous, skilled observers and by the
      operating surgeon in a double-blind fashion. Each patient's photographs were
      accompanied by an identical four-question survey. The survey assessed whether the
      morphed image represented an obtainable goal, the degree of similarity between
      the morphed image and the actual postoperative result, and the quality of the
      surgical outcome as compared with the computer image. RESULTS: As expected based
      on variations in individual surgeons' aesthetic opinions, the cumulative data
      from the 12 blinded raters across all patients indicated that 82 percent of the
      raters would have performed the imaging in either the same way or, at most, a
      "slightly different" way from the operating surgeon. Approximately half thought
      that the computer-morphed image did realistically predict the postoperative
      result but that it could be a bit closer. Seventy-five percent felt that the
      actual surgical result was either the same as or better than the predicted
      result. CONCLUSIONS: Computer imaging for patients undergoing rhinoplasty does
      portray a realistic picture of the anticipated cosmetic result. However, because
      an average of 32 percent of respondents felt that the computer-morphed image did
      not predict the postoperative result, conservative imaging is encouraged to
      prevent false expectations.

PMID- 17496612
TI  - Bariatric surgery: an overview of obesity surgery.

PMID- 17496613
TI  - I want my trophy: setting expectations for life.

PMID- 17496614
TI  - The Pied Piper of Hamelin.

PMID- 17496618
TI  - An anatomical comparison of transpalpebral, endoscopic, and coronal approaches to
      demonstrate exposure and extent of brow depressor muscle resection.

PMID- 17496620
TI  - Antibiotic breast irrigation in breast implant surgery.

PMID- 17496622
TI  - Unusually successive deflation of textured-surface implants.

PMID- 17496623
TI  - One-stage reconstruction of large scalp defect assisted with endoscopic forehead
      lifting and miniscrew external fixation techniques.

PMID- 17496624
TI  - Open rhinoplasty technique for columella defect.

PMID- 17496625
TI  - Bilateral free DIEP breast reconstruction using contralateral internal mammary
      and ipsilateral thoracodorsal vessels.

PMID- 17496626
TI  - A novel tension-reducing suture to protect the T-junction after reduction
      mammaplasty.

PMID- 17496627
TI  - Transareolar and H-incisions for the surgical treatment of gynecomastia.

PMID- 17496628
TI  - Exteriorized pedicle technique in dorsal reverse adipofascial flap for nail
      complex reconstruction.

PMID- 17496629
TI  - Suction-curettage as a surgical treatment of focal axillary hyperhidrosis:
      recommendation for an aggressive approach.

PMID- 17496630
TI  - A new position to hide the abdominoplasty scar.

PMID- 17496631
TI  - Tufted angioma-associated Kasabach-Merritt syndrome treated with embolization and
      vincristine.

PMID- 17496632
TI  - Operative techniques for the minimization of skin graft donor-site pain in flap
      surgery.

PMID- 17496633
TI  - The obsessive patient by proxy.

PMID- 17496634
TI  - Removal of large inclusion cysts with minimal incisional scars.

PMID- 17496635
TI  - Editorial: Before the first Asia-Pacific Symposium on Cochlear Implant and
      Related Sciences (APSCI) ten years ago.

PMID- 17496636
TI  - Ensuring the long-term use of cochlear implants in children: the importance of
      engaging local resources and expertise.
AB  - Cochlear implantation for children is now a mature service, recognized as being
      safe and effective. Early identification is enabling implantation to be
      undertaken in the first years of life, with the likelihood of better outcomes.
      Traditional models of service delivery provided excellent clinic-based services,
      with intensive early habilitation. However, the current challenges extend beyond
      this time frame, and clinic-based services are overstretched with the growing
      numbers of children with implants. Needs analyses of parents and teachers in
      Europe provide evidence that they are keen to have regular links between implant
      center and home and school and that for both parents and teachers a major concern
      is the long-term management of the technology. There are major challenges, not in
      the implant clinic, but at home and school where implant systems are used.
      Implementing complex technology in the child's community in the long term is only
      possible by engaging parents and the local professionals, particularly teachers,
      from the outset, and using their expertise. This calls for a critical appraisal
      of the traditional approach to service delivery. Such engagement of local
      professionals does not happen automatically but can be achieved by educational
      programs for parents and local professionals that are adapted to local needs and
      cultures. Communication between implant center and home and school is essential,
      ensuring that the technology of implantation is used effectively at all times and
      is accessible to all wherever they live. This article recommends ways in which
      parents, teachers, and local professionals can play a central role in the
      management of children with implants to ensure the successful long-term use of
      their implant systems. Engaging and using the skills and expertise of those who
      know the child best, parents and teachers, will not only ensure that implantation
      is sustainable in the long term in diverse cultures, but is also cost-effective.

PMID- 17496637
TI  - Variation in consonant cluster production by pediatric cochlear implant users.
AB  - OBJECTIVE: To provide an account of variation in the production of consonant
      clusters by pediatric cochlear implant users. DESIGN: Productions of consonant
      clusters by pediatric cochlear implant users were analyzed for variation in
      number of segments, reduction patterns, and segmental substitutions within the
      framework of Optimality Theory. RESULTS: A finite set of faithfulness and
      markedness constraints and variable constraint ranking can account for much of
      the variation in the production of consonant clusters by pediatric cochlear
      implant users. CONCLUSION: Variation in consonant cluster production by pediatric
      cochlear implant users is not structurally random but subject to the same
      principles of phonological organization that govern other linguistic systems.

PMID- 17496638
TI  - Communication development in children who receive the cochlear implant younger
      than 12 months: risks versus benefits.
AB  - BACKGROUND: The advent of universal neonatal hearing screening in some countries
      and the availability of screening programs for at-risk infants in other countries
      has facilitated earlier referral, diagnosis, and intervention for infants with
      hearing loss. Improvements in device technology, two decades of pediatric
      clinical experience, a growing recognition of the efficacy of cochlear implants
      for young children, and the recent change in the U.S. Food and Drug
      Administration's age criteria to include children as young as 12 mo has led to
      increasing numbers of young children receiving cochlear implants. Evidence to
      support provision for infants younger than 12 mo is extrapolated from
      physiological studies, studies of children using hearing aids, and studies of
      children older than 12 mo of age with implants. To date, however, there are few
      published research findings regarding communication development in children
      between 6 and 12 mo of age who receive implants. The current study hypothesized
      that earlier implantation would lead to increased rates of language acquisition
      as the children were still in the critical period for their development. METHOD:
      A retrospective review was completed for 19 infants (mean age at implantation,
      0.88 yr; range, 0.61-1.07, SD 0.15) and 87 toddlers (mean age at implantation,
      1.60 yr; range, 1.13-2.00, SD 0.24) who received the multichannel implant in
      Melbourne, Australia. Preimplantation audiological assessments for these children
      included aided and unaided audiograms, auditory brain stem response, auditory
      steady state response (ASSR), and otoacoustic emission and indicated profound to
      total bilateral hearing loss in all cases. Communication assessment included
      completion of the Rossetti Infant-Toddler Language Scale and educational
      psychologists' cognitive and motor assessment. Computed tomography scan, magnetic
      resonance imaging, and surgical records for all cases were reviewed.
      Postimplantation language assessments were reported in terms of the rate of
      growth over time on the language comprehension and language expression subscales
      of the Rossetti Infant-Toddler Language Scale. RESULTS: Results demonstrated that
      cochlear implantation may be performed safely in very young children with
      excellent language outcomes. The mean rates of receptive (1.12) and expressive
      (1.01) language growth for children receiving implants before the age of 12 mo
      were significantly greater than the rates achieved by children receiving implants
      between 12 and 24 mo, and matched growth rates achieved by normally hearing
      peers. These preliminary results support the provision of cochlear implants for
      children younger than 12 mo of age within experienced pediatric implantation
      centers.

PMID- 17496639
TI  - 12-month post-operative results for older children using sequential bilateral
      implants.
AB  - Within a long-term project investigating the perceptual benefits of bilateral
      implants, six children aged 5 to 15 yr received a second implant. Parent reports
      of functional performance were collected, and localization and spondee
      discrimination in noise was assessed. Outcomes varied from no benefit to
      significant benefit, although no improvement in localization was demonstrated. A
      major proportion of the benefit was likely due to headshadow effect. Success did
      not correlate with hearing aid use, age, time between implants, or second implant
      experience.

PMID- 17496640
TI  - Comparison of cognitive function in deaf children between before and after
      cochlear implant.
AB  - OBJECTIVES: This study was conducted to examine improvements of cognitive
      abilities after cochlear implantation in deaf children. We also examined the
      psychosocial factors that predict good outcomes of cochlear implantation. DESIGN:
      A neuropsychological test battery was administered to 17 deaf children (mean age,
      7 yr 2 mo) before receiving the cochlear implant, and they were reassessed with
      the same test at 6-mo follow-up. Their parents completed questionnaires
      concerning their medical and educational history, parenting style, and parental
      emotional problems. RESULTS: Deaf children showed marked improvement in speedy
      and delicate motor coordination and visual organization abilities. Their
      cognitive functions of comprehension, concentration, and sequential processing,
      as measured by nonverbal tests, were found to have improved from the levels of
      borderline to mild mental retardation to that of near-normal range. However,
      their performances on Information, Comprehension and Similarity, and Mathematics
      subtests requiring verbal abilities did not show significant changes. Deaf
      children's working memory improved significantly after cochlear implantation.
      However, they showed more omission errors in the visual attention test at follow
      up than before cochlear implantation. Such inattentiveness for visual stimuli in
      children post-implantation could be attributed to distractibility of these
      children toward external noise. Mothers' depression was negatively correlated
      with scores of acquired knowledge of deaf children. CONCLUSION: At the 6-mo
      follow-up after cochlear implant, deaf children showed marked improvement in
      nonverbal cognitive functions and working memory. Conversely, their verbal
      abilities did not significantly change. Maternal factors were found to be
      important for predicting the prognosis of cochlear implantation. The absence of a
      control group precludes the possibility of drawing any firm conclusions because
      the effect of the implant cannot be teased apart from the effects of maturation
      and training. Future studies should address this question with the use of
      appropriate control groups.

PMID- 17496641
TI  - Music recognition, music listening, and word recognition by deaf children with
      cochlear implants.
AB  - OBJECTIVES: To examine the ability of congenitally deaf children to recognize
      music from incidental exposure and the relations among age at implantation, music
      listening, and word recognition. DESIGN: Seventeen child implant users who were 4
      to 8 yr of age were tested on their recognition and liking of musical excerpts
      from their favorite television programs. They were also assessed on open-set
      recognition of three-syllable words. Their parents completed a questionnaire
      about the children's musical activities. RESULTS: Children identified the musical
      excerpts at better than chance levels, but only when they heard the original
      vocal/instrumental versions. Children's initiation of music listening at home was
      associated with younger ages at implantation and higher word recognition scores.
      CONCLUSIONS: Child implant users enjoy music more than adult implant users.
      Moreover, younger age at implantation increases children's engagement with music,
      which may enhance their progress in other auditory domains.

PMID- 17496642
TI  - The tone production performance of children receiving cochlear implants at
      different ages.
AB  - Sixty prelingually deaf children were tested on Cantonese tone production ability
      at seven time intervals. Results of linear regression showed children in general
      improved in tone production performance over time. The magnitude of improvement,
      nevertheless, was different for children implanted at different ages. For
      children to acquire tone acquisition satisfactory, a critical age of four to
      receive implant is suggested. Optimally, children should receive their implant
      before two where they will be able to achieve around 80% accuracy in tone
      production within 1 yr of implant use. Children received their implant from two
      to just below 4 yr old achieved high tone production accuracy but needed a longer
      duration of implant experience. Children who received their implants at the age
      of 4 yr or older made little, if any, progress in producing tones correctly even
      after four to 5 yr of implant use.

PMID- 17496643
TI  - Using current steering to increase spectral resolution in CII and HiRes 90K
      users.
AB  - OBJECTIVES: The HiResolution Bionic Ear has the capability of creating virtual
      spectral channels using current steering. Through simultaneous delivery of
      current to pairs of adjacent electrodes, it is hypothesized that the effective
      locus of stimulation can be steered to sites between the contacts by varying the
      proportion of current delivered to each electrode of the pair. Thus,
      theoretically, many intermediate regions of stimulation can be created with fine
      control over the proportion and amplitude of current delivered to each electrode.
      This study investigated the number of spectral channels-or different pitches-that
      could be resolved by adult users of the CII and HiRes 90K cochlear implants when
      current steering was applied to three pairs of electrodes along the implanted
      array. DESIGN: Subjects were postlinguistically deafened adults recruited from
      the general CII and HiRes 90K user populations at 11 participating study sites.
      After loudness balancing and pitch ranking electrode pairs (2 and 3, 8 and 9, 13
      and 14), an adaptive paradigm was used to estimate the number of intermediate
      pitch percepts that could be heard for each pair when current steering was
      implemented. Those data were used to estimate the potential number of spectral
      channels for each electrode pair. RESULTS: Data from 57 implanted ears indicated
      that the numbers of spectral channels per electrode pair ranged from one
      (subjects who could not tell the electrodes apart) to 52 (an individual who had
      52 different pitch percepts for the midarray pair of electrodes). The average
      numbers of spectral channels that could be distinguished were 5.4 for the basal
      electrode pair, 8.7 for the midarray electrode pair, and 7.2 for the apical
      electrode pair. Assuming that the average numbers of spectral channels for these
      three electrode pairs were representative of the entire 16-contact array, the
      potential total numbers of spectral channels could be estimated. For the 57 ears,
      the number of potential channels ranged from 8 to 466, with an average of 93.
      CONCLUSIONS: The HiResolution Bionic Ear has the ability to steer current through
      simultaneous stimulation of adjacent electrode contacts. These data show that the
      majority of subjects perceive additional spectral channels other than those
      associated with stimulation of the fixed electrodes when current steering is
      implemented. The results suggest that the average cochlear implant user may have
      significantly more place-pitch capability than is exploited presently by cochlear
      implant systems. Current steering will be implemented in a wearable sound
      processing strategy that can deliver up to 120 spectral channels to CII and HiRes
      90K recipients. The new strategy takes advantage of untapped capabilities of the
      CII/HiRes 90K implanted electronics and will be implemented through software,
      with no additional surgery required. It is anticipated that the improved spectral
      resolution offered by current steering will lead to better speech perception in
      noise and improved music appreciation.

PMID- 17496644
TI  - Comparing neural response telemetry amplitude growth functions with loudness
      growth functions: preliminary results.
AB  - Comparisons of the subjective loudness growth function and the objective evoked
      compound action potential (ECAP) amplitude growth function indicate that both
      functions are exponential in nature. This implies that a more accurate estimate
      of the ECAP threshold would be obtained using exponential regression of the
      amplitude growth function instead of the currently used linear regression. The
      perceptual threshold and the ECAP threshold seem to approach each other when the
      stimulation rate is lowered to reduce temporal summation effects. The effect of
      the stimulation rate on the perceptual threshold will have to be taken into
      account when trying to use the ECAP threshold for predicting the perceptual
      threshold.

PMID- 17496645
TI  - Performance and preference for ACE stimulation rates obtained with nucleus RP 8
      and freedom system.
AB  - Cochlear recently released the Nucleus Freedom System which has been based on the
      Nucleus Research Platform 8. Both systems make use of the same implant, the
      CI24RE, which includes expanded total stimulation rates up to 32 kHz. In this
      study the performance of the ACE strategy at 500, 1200 and 3500 pps/channel was
      investigated using an ABC-CBA design. At the end of each period speech tests were
      performed. In the CBA phase the patients completed a comparative questionnaire to
      determine the subjective rate preference. Preliminary results in 13 recipients
      indicate no differences in for the ACE strategy at rates ranging from 500 pps to
      3500 pps/channel.

PMID- 17496646
TI  - Comparison of musical activities of cochlear implant users with different speech
      coding strategies.
AB  - Speech coding might have an impact on music perception of cochlear implant users.
      This questionnaire study compares the musical activities and perception of
      postlingually deafened cochlear implant users with three different coding
      strategies (CIS, ACE, SPEAK) using the Munich Music Questionnaire. Overall, the
      self-reported perception of music of CIS, SPEAK, and ACE users did not differ by
      very much.

PMID- 17496647
TI  - Performance of older adult cochlear implant users in Hong Kong.
AB  - OBJECTIVE: To compare the speech perception performance of older adults with that
      of adult cochlear implant (CI) recipients in a single center in Hong Kong.
      DESIGN: A retrospective study of 14 older adult CI users (age at operation, 56 to
      77 yr old) and 14 adults (age at operation, 18 to 53 yr old) who received CIs and
      were matched for duration of profound deafness. The outcome indicator of their
      performance includes ratings of 0 to 7 on the speech perception category (SPC),
      which is based on their speech perception test scores at 6, 12, and 24 mo after
      implantation. Statistical analyses were used to compare SPC ratings between the
      two groups at the tested intervals. Results of specific speech perception tests
      between the two groups were also analyzed at the tested intervals, along with the
      rate of improvement of the specific tasks from 0 to 6 mo, 0 to 12 mo, and 0 to 24
      mo postoperatively. Multiple regression analysis was used to assess which
      variables would independently predict the outcome performance of CIs. RESULTS:
      There were no significant differences (p = 0.228 to 0.724) between the SPC
      ratings of the adult group and the older adult group at the tested intervals. The
      adult group scored significantly better in the postoperative 0- to 6-mo
      improvement rate (p = 0.047) in open-set sentence recognition, but the
      improvement decelerated so that it was comparable with that of the older adult
      group by 12 mo after implantation. The adult group also scored significantly
      better (p = 0.031) in tone identification at 24 mo after implantation compared
      with the older adult group. The majority of the speech perception task scores,
      and rates of improvement were comparable between the older adult group and the
      adult group at the tested time intervals. Multiple regression analysis revealed a
      significant relationship (p = 0.025) between the outcome indicator of everyday
      sentence recognition at 12 mo after implantation and the outcome predictor of
      duration of profound deafness. However, the goodness of fit (r) of this model was
      0.11, suggesting that only 11% of the variance in 12-mo postoperative everyday
      sentence recognition was explained by duration of profound deafness, leaving a
      large proportion of unexplained variance. CONCLUSION: : The overall performance
      of the older adult CI recipients is comparable with that of the adult group.
      Duration of profound deafness, irrespective of age, is accountable for a small
      part of the outcome. Because older adults as well as younger adults can benefit
      from CIs, age should not be the predominant factor for declining CIs among older
      adults.

PMID- 17496648
TI  - Age and outcome of cochlear implantation for patients with bilateral congenital
      deafness in a Cantonese-speaking population.
AB  - OBJECTIVE: To evaluate the effect of age at implantation by assessment of speech
      perception in cochlear implant users with bilateral congenital deafness. DESIGN:
      A retrospective cohort analysis of 60 cochlear implant users (age at
      implantation, 1.01 to 22.0 yr) who have at least 2 yr of experience. Their
      outcome performance was defined by the change in i) speech perception category
      (SPC) score based on postoperative assessment results and ii) the type of
      education attended after implantation. The association of age at implantation
      with SPC scores was analyzed at different ages at implantation (2, 3, 4, 5, and 6
      yr old). The SPC scores for a particular age at implantation were compared at 6,
      12, and 24 mo after implantation. The impact of age at implantation on choice of
      education was evaluated by analyzing the transition from a school for the deaf to
      mainstream education for the 45 children who were operated on before the age of
      10, because older children are less likely to make such a change. RESULTS:
      Children implanted at the ages of 2, 3, 4, 5, and 6 yr all obtained significant
      improvements in SPC scores 24 mo after implantation. The greatest improvement was
      noted at 24 mo after implantation among those operated on before age 3. For all
      age groups, improvement at 24 mo after implantation is greater than at 12 mo,
      whereas the latter is greater than the improvement noted at 6 mo after
      implantation. Comparison of children implanted before the age of 3 and between
      ages 3 and 10 showed a significant difference in the choice of education after
      implantation. Children who were implanted before the age of 3 were more likely to
      attend mainstream education after implantation. CONCLUSION: Results from the
      present study are consistent with the current belief that implantation at a
      younger age provides greater benefit. The proportion of children attending
      mainstream education was significantly higher for those implanted before age 3,
      which may be a potential benefit to early implantation for relieving the burden
      of governments in providing special education.

PMID- 17496649
TI  - Comparisons of quality ratings for music by cochlear implant and hearing aid
      users.
AB  - OBJECTIVES: This study aimed to compare the quality ratings by cochlear implant
      (CI) and hearing aid (HA) users in response to musical sounds. DESIGN: The
      ratings of 15 experienced adult Nucleus CI users (using the Advanced Combination
      Encoder (ACE) or Spectral Peak (SPEAK) strategy) were compared with those of 15
      experienced adult HA users who met the audiological criteria for implantation.
      Additionally, nine subjects on the waiting list (WL) for an implant were tested
      before and after implantation. Three types of musical stimuli were used: single
      instruments, solo instruments with background accompaniment, and ensembles. For
      each of these categories, 12 different instruments or ensembles were presented
      four times each. Subjects were asked to provide a rating out of 10 according to
      how pleasant each extract sounded, with 10 being "very pleasant." RESULTS: For
      the WL subjects, ratings provided after implantation were significantly higher
      than their preimplant ratings obtained when using HAs (p = 0.026). This was
      consistent with a trend observed from the experienced CI and HA groups, whereby
      the CI group provided higher ratings than the HA group for all three subtests,
      although the difference was not statistically significant. For all groups, single
      instrument stimuli received significantly higher ratings than those involving
      multiple instruments (CI and HA subjects: p < 0.001; WL subjects: p = 0.034).
      With this research being part of a larger study in which identification testing
      of these stimuli had previously been conducted, significant correlations were
      also obtained between the subjects' ability to identify musical stimuli and the
      corresponding quality ratings (CI: rho = 0.325, p = 0.029; HA: rho = 0.491, p =
      0.001). CONCLUSIONS: The findings of this study suggest that although neither
      device enables highly satisfactory music appreciation, the CI users judged music
      to sound more pleasant than the HA users (who had similar levels of hearing
      impairment). Also, all subject groups appraised music that involved multiple
      instruments to sound less pleasant, on average, than music played by single
      instruments.

PMID- 17496650
TI  - Psychophysical performance and Mandarin tone recognition in noise by cochlear
      implant users.
AB  - OBJECTIVE: The present study was aimed to examine the relationship between
      psychophysical performance in temporal and spectral resolution and Mandarin tone
      recognition in noise by cochlear-implant (CI) listeners. DESIGN: Seventeen
      Nucleus-24 implant users, 10 postlingually deafened and 7 prelingually deafened,
      participated in the experiments. A 3-interval, forced-choice procedure was used
      to measure gap detection and pure-tone frequency discrimination at 250 to 4,000
      Hz in octave steps. A 4-alternative forced-choice procedure was used to measure
      Mandarin tone recognition in quiet and in noise. Signal-to-noise ratios (SNRs)
      varied from +10 to -10 dB. All stimuli were delivered to the clinical processor
      via a speaker in a sound free field. The obtained data were compared to data
      collected from normal-hearing control subjects, as well as cochlear-implant users
      who performed similar tasks using single-electrode stimulation via a research
      interface. RESULTS: Postlingually-deafened CI subjects generally performed better
      than prelingually-deafened subjects. The average gap detection threshold was 30
      ms with a range from 4 to 128 ms. The average frequency difference limen was 100
      Hz with a range from 12 to 192 Hz, regardless of the standard frequency. The
      average tone recognition was 80% correct in quiet, which dropped to 55% at +10 dB
      SNR and essentially chance performance at -5 dB SNR. In comparison, the normal
      hearing control subjects maintained essentially perfect performance over this SNR
      range. Only frequency discrimination at 1,000 Hz was significantly correlated
      with tone recognition in quiet but all psychophysical measures were correlated to
      tone recognition in noise. CONCLUSIONS: The present result suggests that the CI
      users can rely on either temporal or spectral cues to perform tone recognition in
      quiet, but need both cues for tone recognition in noise. Future CI processors
      need to extract and encode these acoustic cues to achieve better performance in
      tone perception and production.

PMID- 17496651
TI  - Telephone speech perception by Mandarin-speaking cochlear implantees.
AB  - OBJECTIVE: To evaluate Mandarin-speaking cochlear implant patients' understanding
      of telephone speech. DESIGN: Telephone speech was simulated by band-limiting
      broadband speech stimuli (300-3200 Hz) and adding Gaussian noise (35 dB signal-to
      noise ratio). Recognition of multitalker vowels, consonants, voice gender, and
      Chinese tones was measured for both simulated telephone speech and broadband
      speech in fifteen Mandarin-speaking cochlear implant patients. RESULTS: Results
      showed no significant difference in Chinese tone recognition scores between
      broadband and telephone speech. However, mean recognition scores for vowels,
      consonants and voice gender were significantly lower with telephone speech. The
      effect of the limited telephone bandwidth on speech recognition was highly
      variable among subjects. Some subjects were more sensitive to high-frequency
      speech cues, resulting in a significant drop in performance with band-limited
      telephone speech, while other subjects were less sensitive to high-frequency
      speech cues, resulting in similar performance between broadband and band-limited
      telephone speech. CONCLUSIONS: These results suggest that the limited bandwidth
      negatively affects cochlear implant patients' understanding of telephone speech.
      Because the effect of band-limited speech was highly variable among subjects, the
      results also suggest that the contribution of high frequency information to
      speech recognition may vary significantly among cochlear implant patients. For
      patients who receive little benefit from high-frequency speech cues, speech
      processor adjustments may be necessary to access the additional cues provided in
      broadband speech.

PMID- 17496652
TI  - Development of the Mandarin Hearing in Noise Test (MHINT).
AB  - OBJECTIVE: To develop two versions of the Mandarin Hearing In Noise Test (MHINT).
      These tests are adaptive tests that measure the reception threshold for sentences
      (RTSs) in quiet and in noise. The RTS is the presentation level at which half the
      sentences are correctly recognized. DESIGN: Four studies were undertaken to (1)
      develop sentence materials, (2) equalize sentence difficulty, (3) create
      phonemically balanced sentence lists; and (4) evaluate within-list response
      variability, inter-list reliability, and produce normative data. A total of 137
      native Mandarin (Putonghua) speaking subjects in Mainland China and 89 native
      Mandarin speakers in Taiwan participated. They had normal hearing thresholds at
      25 dB HL or better. RTSs were measured under four headphone test conditions:
      Quiet, and in noise with noise originating from the 0 degree (Noise Front), 90
      degrees to the right (Noise Right), and 90 degrees to the left (Noise Left). The
      speech originated from the front (0 degree) in all conditions. The noise level
      was fixed at 65 dBA, and the speech was varied adaptively to find the RTS.
      RESULTS: Two versions of the test materials, consisting of 24, 20-sentence lists
      each in Mandarin spoken in the Mainland (the MHINT-M) and the dialect of Mandarin
      spoken in Taiwan (the MHINT-T), were created from two sets of 240 sentences
      containing 10 syllables per sentence. The mean Quiet RTS was 14.7 dBA, using the
      MHINT-M, and 19.4 dBA, using the MHINT-T. Using the MHINT-M, the mean RTS for
      Noise Front was -4.3 dB signal-to-noise ratio (SNR), -11.7 dB SNR for Noise
      Right, and -11.7 dB SNR for Noise Left. Using the MHINT-T, the Noise Front RTS
      was -4.0 dB SNR, -10.7 dB SNR for Noise Right, and -11.0 dB SNR for Noise Left.
      Results in noise are slightly better than those seen for the English HINT norms.
      Response variability within list was low, and inter-list reliability was high,
      indicating that consistent results can be obtained using any list. Confidence
      intervals are reported. CONCLUSIONS: The two versions of the MHINT are the first
      standardized Mandarin sentence speech intelligibility tests. Similar to other
      language versions of the HINT, the MHINT was developed using the same rationale
      as the English HINT, allowing norm-referenced results for the MHINT to be
      compared directly with results in other languages. The MHINT would benefit from
      further evaluation of its validity.

PMID- 17496653
TI  - Quality control after insertion of the nucleus contour and contour advance
      electrode in adults.
AB  - OBJECTIVE: To evaluate the quality of insertion of the Nucleus Contour and the
      newly developed Contour Advance electrode in adult cochlear implant recipients
      and to compare results of speech performance tests with regard to electrode
      position. DESIGN: A total of 43 adult patients with a history of progressive
      hearing loss having received a Nucleus cochlear implant, 21 of which had received
      a Contour electrode and 22 a Contour Advance electrode, were evaluated by
      rotational tomography after surgery. Electrode position was determined to be in
      scala tympani, scala vestibuli, or with a dislocation from one scala to the
      other. Speech test results were collected for Freiburg numbers, Freiburg
      monosyllables, and Oldenburg sentence tests 1 yr after surgery. RESULTS: The
      Contour array presented with a high rate of scala vestibuli insertions and a high
      rate of dislocations from scala tympani to scala vestibuli, whereas the Contour
      Advance array showed a high rate of scala tympani insertions with very few
      dislocations and few scala vestibuli insertions. Speech tests results varied with
      respect to the location of the intracochlear electrode position, with insertions
      into the scala tympani being significantly superior to the scala vestibuli.
      CONCLUSIONS: Results of studying the Contour array influenced the surgical
      procedure that improved surgical ability to perform insertions into the scala
      tympani by using the Contour Advance array. In addition, a comparison between
      Contour and Contour Advance electrode demonstrated an improved mechanical
      behavior of the Contour Advance electrode with a decrease of dislocation rate.
      The use of the Contour Advance electrode allows a more atraumatic electrode
      insertion, which is of interest with extending indications and the use of further
      advanced coding strategies. The intracochlear electrode position with regard to
      speech performance results demonstrated advantages of scala tympani insertions.

PMID- 17496654
TI  - More challenging speech-perception tasks demonstrate binaural benefit in
      bilateral cochlear implant users.
AB  - OBJECTIVE: Preliminary studies show that bilateral cochlear implantation improves
      speech-recognition ability in many subjects; however, the magnitude of this
      improvement has been variable. The objective of our research was to explore means
      to better differentiate the binaural benefit that many patients who receive
      bilateral cochlear implants (CIs) describe. HYPOTHESIS: Binaural improvements in
      speech-perception performance will be consistently evident across patients when
      they are tested in more challenging listening situations. DESIGN: This was a
      prospective clinical study. Speech-perception performance was compared between
      the unilateral and bilateral cochlear implant conditions. Because the purpose was
      to investigate testing parameters that would demonstrate binaural benefit, word-
      and sentence-recognition tests were administered under several stimulation
      conditions: with and without noise and at three presentation levels. In addition,
      all subjects completed the Abbreviated Profile of Hearing Aid Benefit as a
      measure of subjective benefit. Subjects were adult cochlear implant recipients.
      Three device manufacturers were represented (Advanced Bionics Corporation,
      Cochlear Americas, and the Med-El Corporation); three patients received
      simultaneous implantation, and the other four patients received sequential CIs.
      The setting was a comprehensive cochlear implant program/tertiary referral
      center. The main outcomes measures were speech-recognition scores in percent
      correct, mean score difference for unilateral versus bilateral conditions, and
      subjective benefit scores. RESULTS: The most significant improvements in binaural
      cochlear implant use were found when subjects were tested with sentence material
      presented at 60 dB SPL with a +8 dB signal-to-noise ratio. Six of seven subjects
      showed significant binaural improvement, with a mean improvement score of 12.43%
      (SD = 5.32). All subjects preferred the binaural listening condition. Measured
      improvements in quality of life were seen. CONCLUSIONS: Preliminary study
      findings suggest that significant cochlear implant binaural benefit in speech
      perception may be observed when testing in more difficult listening situations
      (i.e., lower presentation levels and in noise). According to the outcome of our
      study, testing the binaural benefit of CIs requires consideration of suitable
      test materials and stimulation parameters.

PMID- 17496655
TI  - Speech perception and localization with adults with bilateral sequential cochlear
      implants.
AB  - This investigation reports measures of binaural hearing of all of our seven
      adults who have received sequential bilateral cochlear implants (range of time
      between implantation of 6 yr/8 mo and 17 yr). All subjects used both devices in
      everyday life. The internal array, number of channels, rate, and signal
      processing strategies were usually quite different between devices. Speech
      recognition was tested by using words in quiet and sentences in noise with the
      sentence stimuli presented from the front and the noise presented from the front,
      the right, or the left at a 90 degrees angle. Bilateral localization was tested
      by using an everyday sounds test with stimuli presented from one of eight
      loudspeakers. Results showed that all subjects received a significant bilateral
      improvement on at least one speech perception test compared to either implant
      alone. Four of seven subjects with bilateral devices demonstrated some (root-mean
      square error below 30 degrees ) localization abilities. The two subjects tested
      unilaterally before receiving a second implant showed a bilateral improvement on
      localization after implantation of the second side. We conclude that sequential
      implants can be beneficial even after many years of monaural use and even with
      very different cochlear implants.

PMID- 17496656
TI  - Standardization of reliability reporting for cochlear implants: an interim
      report.
AB  - OBJECTIVE: To propose a standard definition of "out of specification" for
      cochlear implants and a paradigm for inclusion of category C of the ISO standard
      5841-2:2000 for reporting in cumulative survival statistics. HYPOTHESIS: A
      standard definition of "out of specification" and consistent reporting by
      manufacturers of cochlear implants will create a fair and consistent
      representation of cumulative survival. This will allow discernment of differences
      between manufacturers for reliability and for detection of trends in reliability
      between model types from the same manufacturer. DESIGN: Three separate meetings
      with representatives of the three manufacturers of cochlear implants marketed in
      the United States were staged over a 13-mo period. Standard questions, created by
      the authors, were addressed by each representative to determine the current state
      of device reliability reporting. Results were presented to clinicians at the
      William House Cochlear Implant study Group and the Implantable devices sub
      committee of the American Academy of Otolaryngology (2004, 2005) and at the 8th
      International Cochlear Implant Conference (2004) for feedback. After assimilation
      of feedback by all parties, the standard was written and reviewed by
      representatives from each manufacturer for accuracy of data. RESULTS: A complaint
      driven standard was developed. A "cochlear implant" as an internal device placed
      and skin closed in surgery. An internal device is "out of specification" when one
      or more technical characteristics is outside the limits of normal function and
      results in explantation or non-use by the patient." Children will be reported
      separately from adults, each model of device will be reported on annually, a
      minimum of 200 devices must be in each model group for Cumulative Survival
      Reporting (CSR). Confidence limits are set at 95%. Explants will be determined to
      be "biological" or "technical." Technical explants are included in CSR reports.
      Devices failing to meet specifications set by the manufacturer, not in use but
      still in situ due to patient choice not to be re-implanted are considered
      category C and included in CSR reports. Implants that cannot be classified at
      explant are placed in an "under investigation" category while evaluation is
      completed. If no classification is made by 6 months, these devices will be
      included in the CSR report. Notification to the implant center regarding "in" or
      "out of specification" will be made within 60 d of the explant arriving at the
      manufacturer with final root cause of failure reported to centers when complete.
      Information will be passed on to patients by members of the implant team. A
      standardized form will be created to provide the manufacturers with necessary
      patient information to guide reliability analysis, including performance after re
      implant. CONCLUSIONS: The standard for reliability reporting described in this
      paper improves patient care by presenting data which are understandable to
      clinicians delivering cochlear implant services. It fosters fair and accurate
      reporting without discriminating or granting perceived advantage to any
      manufacturer. This standard provides a basis for reporting research related to or
      including device reliability in the medical literature.

PMID- 17496657
TI  - A multicenter study of device failure in European cochlear implant centers.
AB  - OBJECTIVE: To evaluate the failure rate of cochlear implant systems across a
      range of European implant centers. STUDY DESIGN: Retrospective review. SETTING:
      Tertiary care cochlear implant centers in Europe. MATERIAL AND METHODS: A postal
      questionnaire was designed to assess the incidence and mode of total device
      failure and was sent to 34 European clinics. RESULTS: Twenty seven (79%) centers
      replied providing data on 12,856 devices of which 488 (3.79%) had undergone total
      device failure. Of 8,581 Nucleus devices (Cochlear, Sydney, Australia), 169 had
      failed; of 1,761 Advanced Bionics systems (Advanced Bionics, Sylmar, USA), 123
      had failed; of 1987 Med El devices (Med-El, Innsbruck, Austria), 179 had failed;
      and of 527 MXM devices (Laboratoires MXM, Vallauris, France), 17 had failed. Six
      (22%) centers never reported failures to competent authorities. CONCLUSIONS: The
      study suggests that the overall reliability of cochlear implant systems is
      satisfactory but that reliability varies considerably between individual systems.
      There is a compelling need for agreed international definitions of failure and
      for the adoption of uniform reporting protocols. A common database, independent
      of the industry, would offer greater transparency to users and clinics.

PMID- 17496658
TI  - The totally implantable cochlear implant.
AB  - The concept of a totally implantable cochlear implant (TICI) offers the following
      advantages over the present generation of semi-implantable cochlear implants.
      These advantages include (1) cosmetics: deafness can be "hidden," because there
      is no external hardware during use; (2) no external hardware (e.g., cables,
      speech processor) to fail or be damaged; and (3) hearing possible 24/7, during
      sleep, in the shower, and while swimming. The TICI would incorporate all of the
      current external hardware within the buried device itself. There would also have
      to be external hardware for recharging the batteries and to serve other important
      diagnostic and functional purposes. All of this must be accomplished safely,
      without sacrificing performance.

PMID- 17496659
TI  - Auditory neuropathy: an update.
AB  - OBJECTIVES: To describe the round window electrocochleography (RWECochG) and
      electric auditory brainstem responses (EABR) in ears affected by auditory
      neuropathy (AN), and to determine if these electrophysiological tests can predict
      the outcome following cochlear implant surgery. METHODS: A longitudinal study of
      all pediatric cochlear implant patients between 1994 and 2005 was undertaken.
      Speech perception outcomes after cochlear implantation and electrophysiological
      data were collected prospectively and analyzed. Some otoacoustic emissions (OAE)
      data were collected retrospectively during the neonatal period. All subjects were
      tested using round window electrocochleography (RWEcochG), auditory brainstem
      responses (ABR), and implant-evoked electric auditory brainstem responses (EABR).
      The auditory neuropathy (AN) group consisted of 39 children (78 ears) which had
      present OAE and absent or grossly abnormal ABR (a broad N1 component only).
      RESULTS: All 78 ears from the 39 AN children showed large cochlear microphonics
      (CM) and an abnormal positive potential (APP) using RW ECochG. A further 21
      children showed large CM and APP but had not been tested for OAE. In total, 60
      children were discovered to have APP among 435 pediatric patients who received a
      cochlear implant. Electrically evoked ABR (EABR) from the implanted ear were
      normal in 45 and abnormal in 15. 46 age matched patients without large CM and APP
      were used as a control group. Two year postimplant scores (Melbourne categories)
      were: 6.27 (APP and normal EABR), 2.25 (APP and abnormal EABR) and 5.37 (control
      group). Mann-Whitney U Test for nonparametric data was used to test for
      significant difference at significance level p < 0.005 (two tailed). The APP ears
      which provided normal EABR had significantly better outcomes after cochlear
      implantation than APP ears which had abnormal EABR. Furthermore, the APP ears
      which provided normal EABR performed significantly better after cochlear implant
      surgery than the control group of patients with no OAE, appropriate ABR results
      and normal EABR. CONCLUSIONS: Ears affected by AN provide large CM and APP on RW
      ECochG. The presence of normal EABR may indicate a significantly better outcome
      after cochlear implant surgery than for those APP ears which had abnormal or
      absent EABR. Based on these findings it is suggested that the presence of APP
      and/ or OAE in 75% of the ears which have absent or abnormal ABR may not indicate
      a pathological condition affecting the auditory nerve or synapse but only
      survival of outer hair cells despite extensive loss of inner hair cells.

PMID- 17496660
TI  - Frequency-specific temporal envelope and periodicity components for lexical tone
      identification in Cantonese.
AB  - OBJECTIVES: Temporal envelope and periodicity components (TEPC) in the speech
      signal have potentials to offer important cues for speech recognition especially
      in tonal languages. The aims of this study are: (i) to investigate the degree of
      contributions of TEPC to lexical tone identification in Cantonese; and (ii) to
      investigate whether or not the contributions vary among different frequency
      bands. The results of these investigations would reveal if there are any
      frequency-specific TEPC that are important for lexical tone identification.
      DESIGN: TEPC of monosyllable words carrying different lexical tones, were
      extracted by the method of full-wave rectification and low-pass filtering. They
      were used to modulate a speech spectrum noise to create the test stimuli. Thus
      the stimuli contain only temporal envelope and periodicity components but no
      temporal fine structures of the original speech signal. Multiple sets of stimuli
      were created with different combinations of TEPC modulated frequency bands,
      Eighteen adult subjects with normal hearing participated in the study. RESULTS:
      Lexical tone identification was the best when only the TEPC from the two high
      frequency bands (1-2 kHz and 2-4 kHz) of the original signal were provided, but
      the worst when only the TEPC from the two low frequency bands (60-500 Hz and 500
      1000 Hz) were provided. The findings suggested that high frequency bands are
      carrying TEPC which are important for lexical-tone identification. Lexical tone
      identification performance was better for the male stimuli than the female ones.
      CONCLUSIONS: The results indicate the potential on improving speech recognition
      in tonal languages by manipulating TEPC via new signal processing algorithms in
      hearing prosthesis.

PMID- 17496662
TI  - APSCI panel discussion I: imaging and surgical issues.
AB  - This is a short overview on imaging techniques in pre-, peri- and postoperative
      evaluation of cochlear-implant patients. Surgery techniques are described as well
      as possible complications and how to avoid them.

PMID- 17496661
TI  - Auditory function and speech understanding in listeners who qualify for EAS
      surgery.
AB  - OBJECTIVE: For patients with relatively good low-frequency hearing and relatively
      poor high-frequency hearing, who met the pre-implant criteria for combined
      electric and acoustic stimulation (EAS), our aims were to i) assess deficits in
      low-frequency auditory function, ii) to identify measures which might be
      sensitive to changes resulting from the insertion of an intracochlear electrode
      array, and iii) to quantify the relationship between measures of auditory
      function and performance on tasks of speech and melody recognition. DESIGN:
      Measures of frequency selectivity, temporal resolution, and nonlinear cochlear
      function, along with measures of word, sentence, consonant, vowel, and melody
      recognition, were obtained from 5 normal-hearing and 17 hearing-impaired
      listeners. The hearing-impaired listeners had auditory thresholds at 500 Hz,
      ranging from 20 to 60 dB HL, and thresholds at 1 kHz, ranging from 60 to 100 dB
      HL. RESULTS: Nonlinear cochlear function was either reduced or absent. Frequency
      selectivity at 500 Hz was significantly reduced but still present in most
      patients. Temporal resolution, when measured at low modulation frequencies, was
      normal. Speech recognition in a modulated background revealed significantly
      poorer performance than normal. Speech and melody recognition varied over a large
      range. No measure of auditory function was correlated significantly with speech
      recognition. However, frequency selectivity was related to melody recognition.
      CONCLUSIONS: (1) Patients who qualify for EAS surgery have a wide range of speech
      and melody recognition abilities. (2) A number of the psychophysical measures
      tested may prove more sensitive than the audiogram in determining the degree of
      damage inflicted by the intracochlear electrode array. (3) Speech recognition was
      not correlated with any of the measures of auditory function.

PMID- 17496663
TI  - Evoked potentials in the management of patients with cochlear implants: research
      and clinical applications.
AB  - Evoked potential measures are integral to the treatment of patients with cochlear
      implants. In particular, these techniques are useful in the management of the
      pediatric patient. This brief report describes three categories of evoked
      potentials including clinical and research examples: electrically evoked auditory
      brain stem responses with transtympanic stimulation, middle-latency responses
      with cochlear implant stimulation, and cognitive evoked potentials elicited by
      speech stimuli.

PMID- 17496664
TI  - Panel discussion IV: cochlear implant candidacy, elderly and residual hearing.
AB  - Cochlear implant technology continues to advance, placing new challenges on
      physicians, audiologists, speech-language pathologists, and deaf educators to
      properly determine cochlear implant candidacy. This panel addressed the topics of
      new technology applied to elderly and to very young children. Six panelists were
      selected to represent varied regions of the world, prompting interesting
      discussion and interaction with the audience.

PMID- 17496666
TI  - Effect of training rate on recognition of spectrally shifted speech.
AB  - OBJECTIVE: Previous studies have shown that the protocol used for auditory
      training may significantly affect the outcome of training. However, it is unclear
      how often training should be performed to maximize its benefit. The present study
      investigated how the frequency of training contributed to normal-hearing
      listeners' adaptation to spectrally shifted speech. METHODS: Eighteen normal
      hearing listeners were trained with spectrally shifted and compressed speech via
      an 8-channel acoustic simulation of cochlear implant speech processing. Five
      short training sessions (1 hr per session) were completed by each subject;
      subjects were trained at one of three training rates: five sessions per week,
      three sessions per week, or one session per week. Subjects were trained to
      identify medial vowels presented in a cVc format; depending on the level of
      difficulty, the number of response choices was increased and/or the acoustic
      differences between vowels were reduced. Vowel and consonant recognition was
      measured before and after training as well as at regular intervals during the
      training period. Sentence recognition was measured before and after training
      only. RESULTS: Results showed that pretraining vowel recognition scores were poor
      (14.0% correct, on average) for all subjects, due to the severe spectral shift.
      After five sessions of targeted vowel contrast training, there was a significant
      improvement of shifted vowel recognition for most subjects. The mean improvement
      was comparable (approximately 15 percentage points) across the three training
      rate conditions, despite significant intersubject variability in pre- and
      pretraining baseline performance. There was no significant difference in training
      outcomes among the three training rates. Spectrally shifted consonant and
      sentence recognition also improved by approximately 20 percentage points after
      training, even though consonants and sentences were not explicitly trained.
      Similar to vowel recognition, there was no significant difference in training
      outcomes among the three training rates for shifted consonant and sentence
      recognition. CONCLUSIONS: The results demonstrated that the training rate had
      little effect on normal-hearing listeners' adaptation to spectrally shifted
      speech, at least for the training periods (ranging from 1 to 5 wk) used in the
      present study. The outcome of auditory training may depend more strongly on the
      amount of training (i.e., total number of training sessions) rather than the
      frequency of training (i.e., daily or once per week). Although more frequent
      training may accelerate listeners' adaptation to spectrally shifted speech, there
      may be significant benefits from training as little as one session per week. The
      results of the present study suggest that appropriate training schedules can be
      developed to optimize the effectiveness, efficiency, and effort associated with
      hearing-impaired patients' auditory rehabilitation.

PMID- 17496667
TI  - Personality, hearing problems, and amplification characteristics: contributions
      to self-report hearing aid outcomes.
AB  - OBJECTIVE: When we evaluate the success of a hearing aid fitting, or the
      effectiveness of new amplification technology, self-report data occupy a position
      of critical importance. Unless patients report that our efforts are helpful, it
      is difficult to justify a conclusion that the intervention has been successful.
      Although it is generally assumed that subjective reports primarily reflect the
      excellence of the fitted hearing aid(s) within the context of the patient's
      everyday circumstances, there is relatively little research that assesses the
      validity of this assumption. In previous work, we have reported some
      contributions of the service delivery setting (private practice versus public
      health) to self-report outcomes. The purpose of the present investigation was to
      assess the relative contributions of patient variables (such as personality and
      hearing problems) and amplification variables (such as soft sound audibility,
      gain and maximum output) to self-reports of hearing aid fitting outcomes. DESIGN:
      A cross-sectional survey of 205 patients was conducted with cooperation of eleven
      Audiology clinics. All subjects were recruited when they were seeking new hearing
      aids. Before the hearing aid fitting, measurements of personality and response
      bias were made, as well as measures of hearing problems and expectations about
      amplification. At the fitting, traditional verification data were measured
      including sound field thresholds, preferred gain for conversation, and maximum
      output. Six months after the fitting, a set of 12 standardized self-report
      outcomes was completed. Analyses concerned: (1) the associations among
      personality, response bias, and self-reports about hearing problems that are
      available before the hearing aid fitting, and (2) the associations of these
      precursor variables, and fitting verification data, with self-report data
      assessing the outcome of hearing aid provision. RESULTS: Self-reports of hearing
      problems, sound aversiveness, and hearing aid expectations obtained before the
      fitting were found to be more closely related to the strength of certain
      personality traits than to audiometric hearing loss. Response bias also was
      associated with personality variables. Analyses of the collection of outcome
      measures produced a set of three components that were interpreted as a Device
      component, a Success component, and an Acceptance component. The Device component
      was construed as reflecting characteristics of the hearing aid whereas the two
      other components were construed as reflecting attributes of the wearer. The
      Success and Acceptance components were each significantly associated with several
      personality traits, but the Device component was not associated with personality.
      Variables available before the fitting accounted for 20 to 30% of each outcome
      component whereas amplification variables measured to verify the fitting
      accounted for only 10% on only one component. CONCLUSIONS: As reported in
      previous research, personality is associated with self-report outcome data.
      However, if practitioners utilize existing measures of hearing problems at the
      prefitting stage, separate personality data will not yield additional leverage in
      prediction of long-term fitting outcomes. Traditional fitting verification data
      as measured in this study, proved minimally useful in prediction of long-term
      outcomes of the fitting. A large proportion of variance in self-report fitting
      outcomes has yet to be accounted for. Finally, it appears that certain types of
      questionnaires might be more appropriate for research evaluating new
      amplification devices, whereas a different questionnaire approach might be
      optimal for evaluating intervention effectiveness in a clinical context.

PMID- 17496668
TI  - Clinical evaluation of expanded input dynamic range in Nucleus cochlear implants.
AB  - OBJECTIVE: The aim of this study was to investigate whether expanded
      instantaneous input dynamic ranges (IIDRs) in the Nucleus cochlear implant system
      benefit speech perception in the laboratory and listening in the real world.
      DESIGN: Until recently, Nucleus cochlear implants have used an IIDR of
      approximately 30 dB. In this study, an IIDR of 31 dB was compared with 46 dB and
      56 dB in the SPEAR3 research processor with nine adult implant recipients.
      Subjects were given two, 2-wk blocks of take-home experience with each of the
      three IIDRs. A single IIDR setting was used in each trial period. During the take
      home experience with the expanded IIDRs, subjects used two programs: a standard
      program (with clinically measured electrode dynamic ranges) and a program with
      adjusted thresholds (decreased T levels). After each block of take-home
      experience, speech perception testing was conducted for CNC words in quiet (at 45
      dB and 55 dB SPL) and for CUNY sentences in the presence of multi-taker babble.
      RESULTS: On average, CNC word recognition at low presentation levels was
      significantly better with the 46 dB and 56 dB IIDRs, compared with the 31 dB
      IIDR; however, there was no significant difference between the 46 dB and 56 dB
      IIDR conditions. These benefits were greater for standard programs than for
      reduced T level programs. For CUNY sentences in babble, group results indicated
      no significant difference in performance across IIDR. The three IIDRs were rated
      similarly in real-life listening situations, and two of the subjects expressed
      tolerance problems with the expanded standard IIDRs. CONCLUSIONS: IIDRs of 46 and
      56 dB provided benefit in accessing low-level speech without a decrement in
      sentence perception in babble. Most subjects accepted the standard, wider IIDR
      programs in everyday life. No significant differences were found between the 46
      dB and 56 dB IIDR programs.

PMID- 17496669
TI  - Effects of noise source configuration on directional benefit using symmetric and
      asymmetric directional hearing aid fittings.
AB  - OBJECTIVE: The benefits of directional processing in hearing aids are well
      documented in laboratory settings. Likewise, substantial research has shown that
      speech understanding is optimized in many settings when listening binaurally.
      Although these findings suggest that speech understanding would be optimized by
      using bilateral directional technology (e.g., a symmetric directional fitting),
      recent research suggests similar performance with an asymmetrical fitting
      (directional in one ear and omnidirectional in the other). The purpose of this
      study was to explore the benefits of using bilateral directional processing, as
      opposed to an asymmetric fitting, in environments where the primary speech and
      noise sources come from different directions. DESIGN: Sixteen older adults with
      mild-to-severe sensorineural hearing loss (SNHL) were recruited for the study.
      Aided sentence recognition using the Hearing in Noise Test (HINT) was assessed in
      a moderately reverberant room, in three different speech and noise conditions in
      which the locations of the speech and noise sources were varied. In each speech
      and noise condition, speech understanding was assessed in four different
      microphone modes (bilateral omnidirectional mode; bilateral directional mode;
      directional mode left and omnidirectional mode right; omnidirectional mode left
      and directional mode right). The benefits and limitations of bilateral
      directional processing were assessed by comparing HINT thresholds across the
      various symmetric and asymmetric microphone processing conditions. RESULTS: Study
      results revealed directional benefit varied based on microphone mode symmetry
      (i.e., symmetric versus asymmetric directional processing) and the specific
      speech and noise configuration. In noise configurations in which the speech was
      located in the front of the listener and the noise was located to the side or
      surrounded the listener, maximum directional benefit (approximately 3.3 dB) was
      observed with the symmetric directional fitting. HINT thresholds obtained when
      using bilateral directional processing were approximately 1.4 dB better than when
      an asymmetric fitting (directional processing in only one ear) was used. When
      speech was located on the side of the listener, the use of directional processing
      on the ear near the speech significantly reduced speech understanding.
      CONCLUSIONS: Although directional benefit is present in asymmetric fittings, the
      use of bilateral directional processing optimizes speech understanding in noise
      conditions in which the speech comes from in front of the listener and the noise
      sources are located to the side of or surround the listener. In situations in
      which the speech is located to the side of the listener, the use of directional
      processing on the ear adjacent to the speaker is likely to reduce speech
      audibility and thus degrade speech understanding.

PMID- 17496670
TI  - Hearing impairment and health-related quality of life: the Blue Mountains Hearing
      Study.
AB  - OBJECTIVES: To assess the association between hearing impairment and health
      related quality of life (HRQOL) in an older population, using the self
      administered 36-item Short-Form Health Survey (SF-36). DESIGN: Participants of
      the Blue Mountains Hearing Study (BMHS, N = 2956) attended a comprehensive
      interview and hearing examination in which both self-reported and measured
      hearing impairments were assessed. Hearing impairment was defined as the pure
      tone average of air-conduction hearing thresholds >25 decibels hearing level (dB
      HL) for the four frequencies (0.5 to 4.0 kHz) in the better ear. RESULTS: Of the
      2431 participants with complete data (mean age, 67.0 yr), 1347 (55.4%) did not
      have measured hearing loss, whereas 324 (13.3%) had unilateral (285 mild, 22
      moderate, 17 severe) and 760 (31.3%) had bilateral hearing impairment (478 mild,
      207 moderate, 75 severe). After adjusting for demographic and medical
      confounders, bilateral hearing impairment was associated with poorer SF-36 scores
      in both physical and mental domains (fall in physical component score, PCS of 1.4
      points, p = 0.025; fall in mental component score, MCS of 1.0 point, p = 0.13),
      with poorer scores associated with more severe levels of impairment (PCS p(trend)
      = 0.04, MCS p(trend) = 0.003). Participants with bilateral hearing impairment who
      habitually used hearing aids had a slightly better PCS (mean, 43.1; standard
      error [SE], 0.9) than those with the same impairment who did not have hearing
      aids or who only used them occasionally (mean, 41.2; SE 0.5), although this
      finding was not statistically significant (p = 0.055). Persons with self-reported
      hearing loss had significantly poorer HRQOL than corresponding persons without,
      but persons with unilateral or high-frequency hearing loss did not have
      significantly different HRQOL scores than their corresponding counterparts.
      CONCLUSIONS: This study quantifies the associated disease burden of age-related
      hearing impairment on health-related quality of life in a population-based cohort
      of older persons.

PMID- 17496671
TI  - Development of the Listening in Spatialized Noise-Sentences Test (LISN-S).
AB  - OBJECTIVE: The goals of this research were to develop and evaluate a new version
      of the Listening in Spatialized Noise Test (LISN; Cameron Dillon & Newall, 2006a)
      by incorporating a simplified and more objective response protocol to make the
      test suitable for assessing the ability of children as young as 5 yr to
      understand speech in background noise. The LISN-Sentences test (LISN-S; Cameron &
      Dillon, Reference Note 1) produces a three-dimensional auditory environment under
      headphones and is presented by using a personal computer. A simple repetition
      response protocol is used to determine speech reception thresholds (SRTs) for
      sentences presented in competing speech under various conditions. In four LISN-S
      conditions, the maskers are manipulated with respect to location (0 degrees
      versus +/-90 degrees azimuth) and vocal quality of the speaker(s) of the stories
      (same as, or different than, the speaker of the target sentences). Performance is
      measured as two SRT measures and three "advantage" measures. These advantage
      measures represent the benefit in decibels gained when either talker, spatial, or
      both talker and spatial cues combined, are incorporated in the maskers. This use
      of difference scores minimizes the effects of between-listener variation in
      factors such as linguistic skills and general cognitive ability on LISN-S
      performance. DESIGN: An initial experiment was conducted to determine the
      relative intelligibility of the sentences used in the test. Up to 30 sentences
      were presented adaptively to 24 children ages 8 to 9 yr to estimate the SRT
      (eSRT). Fifty sentences each were then presented at each participant's eSRT, eSRT
      +2 dB, and eSRT -2 dB. Psychometric functions were fitted and the sentences were
      adjusted in amplitude for equal intelligibility. After adjustment,
      intelligibility increased across sentences by approximately 17% for each 1 dB
      increase in signal-to-noise ratio (SNR). A second experiment was conducted to
      gather normative data on the LISN-S from 82 children with normal hearing, ages 5
      to 11 yr. RESULTS: For the 82 children in the normative data study, regression
      analysis showed that there was a strong trend of decreasing SRT and increasing
      advantage as age increased across all LISN-S performance measures. Analysis of
      variance revealed that significant differences in performance were most
      pronounced between the 5-yr-olds and the other age groups on the LISN-S measures
      that assess the ability to use spatial cues to understand speech in background
      noise, suggesting that binaural processing skills are still developing at age 5
      yr. Inter-participant variation in performance on the various SRT and advantage
      measures was minimal for all groups, including the 5- and 6-yr-olds who exhibited
      standard deviations ranging from only 1.0 dB to 1.8 dB across measures. The intra
      participant standard error ranged from 0.6 dB to 2.0 dB across age groups and
      conditions. Total time taken to administer all four LISN-S conditions was on
      average 12 minutes. CONCLUSIONS: The LISN-S provides a quick, objective method of
      measuring a child's ability to understand speech in background noise. The small
      degree of inter- and intra-participant variation in the 5- and 6-yr-old children
      suggests that the test is capable of assessing auditory processing in this age
      group. However, because there appears to be a strong developmental curve in
      binaural processing skills in the 5-yr-olds, it is suggested that the LISN-S be
      used clinically with children from 6 yr of age. Cut-off scores, calculated as 2
      standard deviations below the mean adjusted for age, were calculated for each
      performance measure for children ages 6 to 11 yr. These scores, which represent
      the level below which performance on the LISN-S is considered to be outside
      normal limits, will be used to in future studies with children with suspected
      central auditory processing disorder.

PMID- 17496672
TI  - A randomized controlled trial evaluating the active communication education
      program for older people with hearing impairment.
AB  - OBJECTIVE: To evaluate the effectiveness of the Active Communication Education
      (ACE) program for older people with hearing impairment and to investigate factors
      that influence response to the program. The ACE is a group program that runs for
      2 hr per week for 5 wk. DESIGN: In this double-blinded, randomized, controlled
      trial, 178 older people with, on average, mild to moderate hearing impairment
      were randomly allocated to one of two groups. Approximately half had been fitted
      with hearing aid/s in the past. One group (N = 78) undertook a placebo social
      program for the first 5 wk, followed by the ACE program. They were assessed
      before the social program, immediately after it, and then again immediately post
      ACE. The other group (N = 100) undertook the ACE program only and were assessed
      before and after ACE. In addition, 167 participants were reassessed 6 mo after
      completing ACE. Assessments were all self-report and included two sets of
      measures: 1) those administered both before and after the program-the Hearing
      Handicap Questionnaire, the Quantified Denver Scale of Communicative Function,
      the Self-Assessment of Communication, the Ryff Psychological Well-Being Scale,
      the Short-Form 36 health-related quality of life measure; and 2) those
      administered postprogram only-the Client Oriented Scale of Improvement, the
      International Outcome Inventory-Alternative Interventions, and a qualitative
      questionnaire. All assessments were conducted by a researcher blinded to
      participants' group membership. The relationships between participant response to
      the ACE program and a number of client-related factors were also investigated.
      These factors were the participants' age, gender, hearing loss, hearing aid use,
      attitudes to hearing impairment (as measured using the Hearing Attitudes to
      Rehabilitation Questionnaire) and the involvement of significant others. RESULTS:
      For those participants who completed the social program initially, significant
      improvements were found on the Quantified Denver Scale of Communicative Function
      and on the Mental Component Score of the Short-Form 36 only, when pre- and
      postprogram scores were compared. For those who completed the ACE program, there
      were significant pre-to-post improvements on the Hearing Handicap Questionnaire,
      the Quantified Denver Scale of Communicative Function, the Self-Assessment of
      Communication, and the Ryff Psychological Well-Being Scale. These improvements
      after ACE were maintained at 6 mo. Higher scores on the Hearing Attitudes to
      Rehabilitation Questionnaire before the ACE program were associated with greater
      positive change on a number of the pre-post program measures. Using the Client
      Oriented Scale of Improvement, 75% of participants reported some improvement on
      the primary goal they wished to achieve with the ACE. Positive outcomes were also
      recorded with the International Outcome Inventory-Alternative Interventions.
      CONCLUSIONS: This research study provides evidence for the effectiveness of the
      ACE program and indicates that such communication programs have an important
      place in the audiological rehabilitation of older adults. They should be
      considered as an alternative or a supplement to traditional interventions such as
      hearing aid fitting.

PMID- 17496673
TI  - Prevalence of dead regions in subjects with sensorineural hearing loss.
AB  - OBJECTIVE: To estimate the prevalence of dead regions in adult subjects with
      sensorineural hearing impairment as a function of audiometric threshold and
      frequency and to assess the extent to which the presence/absence of a dead region
      can be predicted from the audiogram, gender, or age. DESIGN: Data were obtained
      from a random sample of adults attending an audiology clinic in Mysore, India.
      Audiometric air and bone conduction thresholds and tympanometry were used to
      identify 317 subjects (592 ears) with sensorineural hearing loss. Their ages
      ranged from 17 to 95 yr (mean = 57 yr). The threshold-equalizing noise hearing
      level (TEN (HL)) test, administered using the TEN(HL)-test CD and an audiometer,
      was used to determine the presence or absence of dead regions in these subjects
      for test frequencies ranging from 0.5 to 4 kHz. Nine subjects had to be excluded
      as the absolute thresholds were too high for the TEN(HL) test to be administered.
      Of the remaining 308 subjects (556 ears), 209 (68%) were male and 99 (32%) were
      female. The hearing losses ranged from mild to severe. RESULTS: Results are
      presented only for frequencies and ears for which the TEN level could be made
      high enough to produce at least 10 dB of masking. Classifying by subject, 177
      (57.4%) were found to have a dead region in one or both ears for at least one
      frequency. Fifty-four women (54.5%) and 123 men (58.8%) had dead regions in one
      or both ears. Classifying by ear, 256 (46%) were diagnosed as having a dead
      region at one frequency or more: 233 ears (41.9%) had only a high-frequency dead
      region, 13 ears (2.3%) had only a low-frequency dead region, and 10 ears (1.8%)
      had a dead region at both low and high frequencies, with a surviving middle
      frequency region. It was not possible to achieve both high sensitivity and high
      specificity when attempting to predict the presence/absence of a dead region from
      the audiogram. However, for each test frequency, 59% or more of ears had a dead
      region when the absolute threshold was above 70 dB HL. A very steep slope of the
      audiogram is suggestive of a high-frequency dead region but does not provide a
      reliable diagnostic method. Chi-square tests indicated that the prevalence of
      dead regions did not vary significantly with age or gender. CONCLUSIONS: The
      results indicate a relatively high prevalence of dead regions in adults with
      sensorineural hearing impairment, especially for frequencies at which the hearing
      loss exceeds 70 dB HL.

PMID- 17496674
TI  - Neuromonics Tinnitus Treatment: third clinical trial.
AB  - OBJECTIVES: The Neuromonics Tinnitus Treatment combines the use of a novel
      approach to acoustic stimulation with a structured program of counseling and
      support by a clinician specifically trained in tinnitus rehabilitation. The
      distinctive acoustic component has been designed to provide stimulation to
      auditory pathways deprived by hearing loss, engage positively with the limbic
      system, and allow intermittent, momentary tinnitus perception within a pleasant
      and relaxing stimulus, thereby facilitating desensitization to the tinnitus
      signal. The purposes of this study were (1) to demonstrate the efficacy of the
      treatment, when enhanced with various modifications since previously reported
      trials and (2) to test the relative clinical effectiveness of two variations of
      the approach. In the first, intermittent tinnitus perception was facilitated
      throughout treatment through the use of a stimulus in which intensity peaks
      allowed the patients' tinnitus perception to be completely covered up, whereas in
      the intensity troughs their tinnitus was briefly discernible. In the second,
      subjects experienced little tinnitus perception while listening to the treatment
      for the first 2 mo, then experienced intermittent perception. DESIGN: Thirty-five
      subjects with a predominantly moderate to severe level of tinnitus-related
      distress before treatment were randomly allocated into one of two treatment
      groups, corresponding to the two stage-based variations of the Neuromonics
      Tinnitus Treatment. Participants were provided with a high-fidelity personal
      sound player with earphones and an acoustic stimulus that had been spectrally
      modified according to their individual audiometric profile. They were instructed
      to use the acoustic stimulus for at least 2 hr per day, particularly at those
      times when their tinnitus was usually disturbing. Each group had equal amounts of
      clinician time for education, monitoring, and support. RESULTS: At 2, 4, 6, and
      12 mo after commencing treatment, both groups displayed clinically and
      statistically significant improvements in tinnitus distress, awareness, and
      minimum masking levels as well as loudness discomfort levels. Improvements
      increased with time over the first 6 mo of therapy, at which time 91% of all
      subjects across the two groups reported an improvement in tinnitus disturbance
      (as measured by the Tinnitus Reaction Questionnaire) of at least 40%, with a mean
      improvement of 65%. Also, 80% of subjects at 6 mo reported a level of tinnitus
      disturbance that was no longer clinically significant. There was some indication
      of a more consistent benefit over 12 mo for the group that was provided initially
      with a high level of tinnitus interaction; however, inter-group differences were
      not statistically significant. A relation between reported treatment usage (hours
      per day) and clinical outcomes was observed, suggesting that a "dosage effect"
      may apply with the stimulus provided. CONCLUSIONS: This study found that the
      Neuromonics Tinnitus Treatment provides rapid and profound improvements to the
      severity of tinnitus symptoms and their effect on the subject's quality of life.
      This was a consistent effect, provided by a treatment that subjects reported as
      being pleasant to use. Both of the stage-based variations of the treatment that
      were tested in this study were shown to be successful in achieving these
      outcomes.

PMID- 17496677
TI  - Detection of occult pneumothoraces in the significantly injured adult with blunt
      trauma.
AB  - BACKGROUND: Identification of pneumothoraces is essential during the initial
      assessment of major injury. Prompt intervention is crucial for effective
      resuscitation and for subsequent safe management. Historically, emergency
      departments have relied on chest X-ray for detection of pneumothoraces. More
      recently, the increasing availability of computed tomography (CT) has provided a
      more sensitive means of detection. Occult pneumothoraces are those that are
      missed on clinical examination and chest X-ray, but are detected on subsequent
      CT. OBJECTIVE: To determine the incidence of occult pneumothoraces and their
      impact on subsequent management. PATIENTS: All blunt trauma patients with CT
      scans from a single, large, adult emergency department in 1 year. METHODS:
      Patient records were analysed to determine the proportion of pneumothoraces
      detected on CT that had not been previously detected on chest X-ray. Records were
      further examined to determine how many occult pneumothoraces required additional
      management after detection. RESULTS: In all, 134 blunt trauma patients required a
      CT scan. Thirty-five pneumothoraces were detected in 27 patients; 15 were occult.
      Six of these 15 were managed with intercostal drain insertion, all proceeding to
      mechanical ventilation. Of the eight patients (one bilateral) managed
      observantly, all had uncomplicated recoveries. CT was significantly more
      sensitive in the detection of pneumothoraces (P=0.03). Retrospective review by a
      radiology specialist identified three chest X-rays that had findings (deep sulcus
      sign and prominent cardiac outline) that were suggestive of pneumothorax.
      CONCLUSIONS: A sufficiently high proportion of pneumothoraces is missed on chest
      X-ray to advocate a low threshold for use of CT in the early assessment of blunt
      trauma patients, especially if mechanical ventilation is required for ongoing
      management.

PMID- 17496675
TI  - Performance of patients using different cochlear implant systems: effects of
      input dynamic range.
AB  - OBJECTIVE: To determine, for patients who had identical levels of performance on
      a monosyllabic word test presented in quiet, whether device differences would
      affect performance when tested with other materials and in other test conditions.
      DESIGN: For Experiment 1, from a test population of 76 patients, three groups (N
      = 13 in each group) were created. Patients in the first group used the CII Bionic
      Ear behind-the-ear (BTE) speech processor, patients in the second group used the
      Esprit3G BTE speech processor, and patients in the third group used the Tempo+
      BTE speech processor. The patients in each group were matched on (i) monosyllabic
      word scores in quiet, (ii) age at testing, (iii) duration of deafness, and (iv)
      experience with their device. Performance of the three groups was compared on a
      battery of tests of speech understanding, voice discrimination, and melody
      recognition. In Experiments 2 (N = 10) and 3 (N = 10) the effects of increasing
      input dynamic range in the 3G and CII devices, respectively, was assessed with
      sentence material presented at conversational levels in quiet, conversational
      levels in noise, and soft levels in quiet. RESULTS: Experiment 1 revealed that
      patients fit with the CII processor achieved higher scores than Esprit3G and
      Tempo+ patients on tests of vowel recognition. CII and Tempo+ patients achieved
      higher scores than Esprit3G patients on difficult sentence material presented in
      noise at +10 and +5 dB SNR. CII patients achieved higher scores than Esprit3G
      patients on difficult sentence material presented at a soft level (54 dB SPL).
      Experiment 2 revealed that increasing input dynamic range in the Esprit3G device
      had (i) no effect at conversational levels in quiet, (ii) degraded performance in
      noise, and (iii) improved performance at soft levels. Experiment 3 revealed that
      increasing input dynamic range in the CII device improved performance in all
      conditions. CONCLUSIONS: Differences in implant design can affect patient
      performance, especially in difficult listening situations. Input dynamic range
      and the method by which compression is implemented appear to be the major factors
      that account for our results.

PMID- 17496678
TI  - Were attendances to accident and emergency departments in England and Australia
      influenced by the Rugby World Cup Final 2003?
AB  - OBJECTIVES: To determine changes in volume and timing of accident and emergency
      (A&E) attendances associated with the Rugby World Cup Final 2003. METHODS:
      Retrospective analysis of A&E attendance data from the West Midlands Surveillance
      Centre and the New South Wales Emergency Department Collection. SETTING: West
      Midlands, England and New South Wales, Australia. MAIN OUTCOME MEASURES: Relative
      risk of accident and emergency attendance during a 18-h period in 2003 compared
      with the same 18-h period in the years 2000-2002. RESULTS: In the West Midlands,
      in the 2 h before kick-off there were 72 attendances compared with an expected
      101 in 2000-2002 [relative risk (RR) 0.71, 95% confidence interval (CI) 0.55
      0.89]. For New South Wales, there were 326 attendances compared with an expected
      384 (RR 0.85, 95% CI 0.76-0.95). The West Midlands saw a significant increase in
      attendance peaking 6-8 h after the kick-off (RR 1.27, 95% CI 1.10-1.46).
      CONCLUSION: In the West Midlands, it appears that attendance was reduced in the
      hours immediately surrounding the final, but in subsequent hours attendances
      increased, potentially as a result of celebration of the win. In New South Wales,
      the final was associated with reduced attendance in the hours leading up to the
      final, but they quickly returned to normal. Major sporting events can influence
      accident and emergency workload.

PMID- 17496679
TI  - Intracranial stab wound: a case report.
AB  - OBJECTIVE: Intracranial stab wounds are relatively uncommon, as the adult skull
      usually provides an effective barrier to penetration. We present an interesting
      case of a penetrating intracranial stab wound with several important teaching
      points. CLINICAL PRESENTATION: A 44-year-old man presented to the emergency
      department with a 1.2-cm stab wound to the left temporal area. His initial
      Glasgow Coma Score was 14/15. Computerized tomography of his brain revealed a
      left temporal lobe haemorrhage and contusion. Magnetic resonance images of his
      brain revealed a linear haematoma extending from his left temporal lobe into the
      left middle cerebellar peduncle, consistent with a penetrating injury. He was
      managed conservatively with intravenous antibiotics and made an excellent
      recovery. Three weeks after injury, he had mild residual problems with recall and
      attention. CONCLUSION: Several leaning points exist in this case. Firstly, as
      stab wounds to the brain frequently present as apparently innocuous facial or
      scalp lacerations, a high index of suspicion is needed to prevent these injuries
      presenting with serious late infective complications. Secondly, reports of
      similar cases in the literature suggest that stab wounds to the temporal region
      are associated with a high morbidity and mortality. This case demonstrates that a
      patient with an injury such as this can occasionally make a good functional
      recovery. Finally, this case highlights the advantage of magnetic resonance
      imaging over computerized tomography in patients with these injuries once it has
      been established that there is no residual intracranial metal fragment prior to
      magnetic resonance imaging. In this case, the entire wound tract was only evident
      on magnetic resonance imaging and not on the initial computerized tomography
      scans.

PMID- 17496680
TI  - Adherence to resuscitation guidelines during prehospital care of cardiac arrest
      patients.
AB  - OBJECTIVE: The impact of prehospital care after the return of spontaneous
      circulation in out-of-hospital cardiac arrest patients is not known. This study
      describes adherence to the resuscitation guidelines, factors associated with poor
      adherence and possible impact of prehospital postresuscitation care on the
      outcome of out-of-hospital cardiac arrest. METHODS: One hundred and fifty-seven
      Finnish out-of-hospital cardiac arrest patients hospitalized during 1 year, were
      analyzed retrospectively. Patient and arrest characteristics, prehospital
      postresuscitation care and survival to hospital discharge were analyzed using
      multivariate logistic regression. RESULTS: Forty percent of the patients received
      care accordant with the guidelines. Male sex (P=0.045), witnessed arrest
      (P=0.031), initial ventricular fibrillation/ventricular tachycardia rhythm
      (P=0.007) and the presence of an emergency physician (P=0.017) were associated
      with care in line with the current guidelines. In multivariate logistic
      regression analysis, age over median (odds ratio=3.6, 95% confidence interval 1.5
      8.6), nonventricular fibrillation/ventricular tachycardia initial rhythm (odds
      ratio=4.0, 95% confidence interval 1.6-9.8), administration of adrenaline (odds
      ratio=7.0, 95% confidence interval 2.3-21.4) and unsatisfactory prehospital
      postresuscitation care (odds ratio=2.5, 95% confidence interval 1.1-6.3) were
      associated with a failure to survive up to hospital discharge. CONCLUSIONS: Less
      than 50% of out-of-hospital cardiac arrest patients received prehospital
      postresuscitation care compatible with the current guidelines. Markers of poor
      prognosis were associated with unsatisfactory care, which in turn was more
      frequent among the patients who did not survive to hospital discharge. The
      importance of the guidelines should be highlighted in the future.

PMID- 17496681
TI  - Is routine electrolyte testing necessary for diabetic patients who present to the
      emergency department with moderate hyperglycemia?
AB  - OBJECTIVES: No consensus standard is established for the workup of diabetic
      patients with moderate hyperglycemia [fingerstick glucose of 11.00-33.00 mmol/l
      (200-600 mg/dl)]. We measured the incidence of serious electrolyte abnormalities
      in patients with moderate hyperglycemia and attempted to identify a subset of
      these patients who can safely forego routine electrolyte testing. METHODS:
      Prospective cohort study in two affiliated emergency departments. INCLUSION
      CRITERIA: Moderate hyperglycemia. EXCLUSION CRITERIA: new onset diabetes or renal
      failure. The composite outcome was defined as an abnormal potassium K >5.00 or
      <3.50 mmol/l or diabetic ketoacidosis. Univariate analyses were performed using t
      test and Fisher's exact test (alpha=0.05, two-tails). Logistic regression models
      were generated to identify variables that could predict the composite outcome.
      RESULTS: Three hundred and ninety-nine adults were enrolled (294 type II, 38%
      men). Mean age was 59+/-15 (20-97 years) years. The incidence of the composite
      outcome was 22% (95% confidence interval, 17.8-26.0%, n=86). The univariate
      analysis identified potassium-altering medications and insulin use as risk
      factors for the composite outcome. Logistic regression analysis identified
      potassium-altering medications as an increased risk (relative risk: 1.64, 95%
      confidence interval, 1.14-2.37) and use of oral hypoglycemics as a decreased risk
      (relative risk: 0.62, 95% confidence interval, 0.43-0.90) of the composite
      outcome. Cross-validation of the model demonstrated poor sensitivity (76%) and
      even worse accuracy (51%). CONCLUSION: We failed to identify any subgroup of
      patients with moderate hyperglycemia who can be safely excluded from routine
      electrolyte testing. We recommend routine electrolyte testing for all moderate
      hyperglycemia patients in the emergency department.

PMID- 17496682
TI  - Severe disseminated intravascular coagulation caused by congestive heart failure
      and left ventricular thrombus.
AB  - We present a patient who visited emergency department owing to the skin
      manifestation of disseminated intravascular coagulation. Recent anterior
      myocardial infarction induced congestive heart failure and left ventricular
      thrombus, which were considered to be the cause of disseminated intravascular
      coagulation. Anticoagulant therapy with heparin and warfarin was used
      successfully to treat the disseminated intravascular coagulation and left
      ventricular thrombus.

PMID- 17496683
TI  - A complete tear of the pectoralis major muscle from a seat belt injury.
AB  - Rupture of the pectoralis major muscle is a rare injury that can result in both
      functional and cosmetic deficiency, with fewer than 150 cases reported in the
      literature. To date, the injury has been reported exclusively in men and is most
      common among weight lifters and high-performance athletes. The treatment of
      partial rupture is conservative, whereas in cases of total rupture surgical
      repair is advocated, particularly in young active patients. Here, we report the
      case of a complete proximal tear of the pectoralis major muscle from a seat belt
      injury sustained in a motor vehicle accident. To the best of our knowledge, this
      is the first time such a case has been reported in the literature.

PMID- 17496684
TI  - Terminal ileum perforation from a misplaced percutaneous suprapubic cystostomy.
AB  - Iatrogenic bowel injury is a recognized complication of percutaneous suprapubic
      cystostomy. In the present report, we report an unusual case of small bowel
      perforation caused by a misplacement of suprapubic catheter into terminal ileum.
      For safe placement of a suprapubic catheter, the patients must have an adequately
      distended bladder and be placed in Trendelenburg position that allows safe
      extraperitoneal puncture of the bladder.

PMID- 17496685
TI  - Emergency ultrasound and gallstone ileus.
AB  - Gallstone ileus is an uncommon cause of mechanical obstruction due to a biliary
      stone that wedges the intestinal lumen. It is a surgical emergency representing a
      clinical and diagnostic challenge: the clinical manifestations are rarely
      specific, often causing diagnostic delay that can adversely affect the prognosis.
      Emergency ultrasound could be useful in assessing the level and identifying the
      cause of bowel obstruction. We report a case of a 74-year-old patient with a 6
      day history of constipation and crampy abdominal pain without previous history of
      abdominal diseases. Emergency ultrasound led to an early diagnosis showing
      dilated small bowel loops with a shadowing mass inside consistent with an ileal
      stone, in the absence of aberrant located stone on plain abdominal film.

PMID- 17496686
TI  - Rupture of the right main bronchus: a case of a 4-year-old girl.
AB  - Tracheobronchial rupture after a blunt chest trauma is rare, especially in
      children. If the diagnosis is overlooked, severe ventilatory complications or
      mediastinitis may occur. We describe a case of a 4-year-old girl with a rupture
      of the right main bronchus after she was hit by a frame of steel (like a mini
      goal) that fell down while she was playing. The diagnosis was initially missed
      owing to a variety of symptoms. Difficulty with ventilation and persistent air
      leak after insertion of a chest tube in the case of a pneumothorax is suspect for
      a tracheobronchial rupture. This emphasizes once again the importance of the
      concept of rechecking and searching for the underlying cause when a pneumothorax
      persists. Bronchoscopy is the gold standard in establishing the diagnosis.
      Surgical treatment is in most cases the best option, especially in a ventilated
      patient. Without treatment mortality rates are up to 30%. In conclusion,
      tracheobronchial rupture should be excluded if mediastinal emphysema or a
      persistent air leak is present after a blunt thoracic trauma.

PMID- 17496687
TI  - Economy class syndrome: still a recurrent complication of long journeys.
AB  - Economy class syndrome is a rare but still unavoidable complication of long haul
      flights, particularly in patients who carry various intrinsic risk factors. The
      tendency to affect even asymptomatic young people and the greater risk to
      fragment and propagate to the pulmonary circulation are the main characteristics
      of deep vein thrombosis of long-flight travelers. We report the clinical history
      of eight patients admitted to intensive care unit for confirmed or highly
      suspected economy class syndrome. Seven of them developed the syndrome within 72
      h from a long return flight, one suffered from pulmonary embolism after a 12-h
      car trip. Two out of eight patients died, one because of extremely severe
      hemodynamic impairment, the other as a consequence of multiple organ failure
      caused by a concomitant myocardial infarction. Deep vein thrombosis and pulmonary
      embolism represent one of the main medical problems of air travel and cause
      almost 20% of deaths in people with no medical history. Although economy class
      syndrome occurs mostly in elderly, even the healthy young population can be
      affected and, in fact, three out of eight patients of our series were under 50
      years of age. All our patients but one carried a well recognized risk factor for
      deep vein thrombosis. Clinical symptoms of deep vein thrombosis can sometimes be
      aspecific and confusing, so that a certain proportion of post-travel deep vein
      thrombosis, evolving favorably and not giving rise to pulmonary embolism, might
      effectively remain undiagnosed. Economy class syndrome is still quite difficult
      to deal with and controversial in terms of preventive strategies.

PMID- 17496688
TI  - A case of mesenteric panniculitis: multiple involvement of the emergency
      department before final diagnosis and appropriate treatment.
AB  - Mesenteric panniculitis is a rare disease leading to recurrent acute abdominal
      pain, whose recognition is important to avoid any unwarranted aggressive surgery.
      A case of this condition is described. The patient, a 73-year-old man, attended
      our emergency room with acute abdominal pain, fever and prolonged partial
      thromboplastin time. He had a history of recurrent emergency department access
      and complained of the same rapidly reversible clinical picture. Findings at
      abdominal computed tomography and at diagnostic laparascopy (including histology
      of a biopsy) helped reach a correct diagnosis and treatment. In this brief report
      from literature analysis, we present diagnosis and treatment of mesenteric
      panniculitis from what is known so far. Finally, we briefly discuss some peculiar
      pathogenesis and hypothesis.

PMID- 17496689
TI  - Chemical burn in domestic setting with an uncommon agent: hydrofluoric acid.
AB  - Chemical burns, in particular because of hydrofluoric acid, are not common in the
      pediatric emergency department. Here, we describe an infant presenting with
      digital ischemic findings owing to late diagnosis of hydrofluoric acid splash in
      domestic setting.

PMID- 17496690
TI  - Methods of assessing cardiopulmonary resuscitation skills: a systematic review.
AB  - Valid and reliable instruments are needed for assessment and comparison of
      training outcomes after various methods of cardiopulmonary resuscitation
      training. Trials were retrieved by searching MEDLINE (1990-February 2005) and
      using the reference lists of original communications and reviews. Studies were
      considered relevant if they included an intervention, a study population of life
      support providers randomized and divided into groups and an evaluation or
      assessment of the performance. The studies were analyzed and scored to assess
      their validity. Twenty-five studies fulfilled the criteria. Nineteen of them
      assessed cardiopulmonary resuscitation skills, four cardiopulmonary resuscitation
      and defibrillation and two assessed defibrillation only. The mean number of
      participants was 107 (range 36-495). A wide variety of assessment methods were
      used in the studies with methodological shortcomings. Most studies in this review
      compared participants with each other, not against a standard or a defined
      passing level. Qualified studies with well defined study populations,
      standardized study settings and explicit, comparable outcomes would be needed to
      assess the quality of cardiopulmonary resuscitation and defibrillation
      performance.

PMID- 17496691
TI  - Mass gathering medicine for the First East Asian Football Championship and the
      24th European/South American Cup in Japan.
AB  - It is very important to collect and accumulate data of same-type events from the
      point of view of appropriate preparedness for mass gathering medicine. On the
      basis of the experience of the 2002 FIFA World Cup Korea/Japan, the Japanese
      Association of Disaster Medicine organized the emergency medical assistance team
      during large football events. The objective was to analyze all clinical
      presentations available to the on-site physicians during this event. The total
      number of patients was 51 (patient presentation rate: 0.25/1000 spectators).
      Trauma, abdominal pain and common cold were the main pathologies encountered.
      Eight patients were transported to hospital. Forty-one patients (80.4% of total)
      were treated within the medical station and were not transported to hospital.
      These dispositions were considered to lighten the burden imposed on activities of
      local emergency medical services. Sharing databases with local medical services
      and surveying the outcome of patients are needed to allow patient presentation
      provision.

PMID- 17496692
TI  - Spontaneous pneumomediastinum as a result of SCUBA diving.

PMID- 17496693
TI  - Near-fatal betaxolol self-poisoning treated with percutaneous extracorporeal life
      support.
AB  - We present a case of successful treatment of near-fatal beta-blocker self
      poisoning but requiring extracorporeal circulatory support with severe
      complications. A 38-year-old woman ingested a mixture of tablets including
      betaxolol (5.32 g). Despite intensive treatment with fluid, dobutamine,
      isoprenaline, epinephrine, nor-epinephrine and glucagon, sustained cardiogenic
      shock occurred with almost complete hypokinesia of the left ventricular 14 h
      later. Therefore, a cardiac support was performed with a percutaneous
      cardiopulmonary bypass device at bedside. We review the literature with emphasis
      on both the best time to start this technique and its complications.

PMID- 17496694
TI  - Bilateral spontaneous pneumothorax in a patient with ankylosing spondylitis.

PMID- 17496696
TI  - Novel method for determining hydrogel and silicone hydrogel contact lens
      transmission curves and their spatially specific ultraviolet radiation protection
      factors.
AB  - PURPOSE: Anterior ocular tissues exposed to high levels of toxic ultraviolet (UV)
      radiation may undergo physiologic changes leading to diseases that can alter the
      ocular surface, particularly in the stem cell-rich limbal region. UV radiation
      blocking hydrogel contact lenses provide protection across the ocular surface,
      which varies according to the lens thickness. METHODS: A novel fiber optic
      spectrophotometer front-end system has been developed to measure lens
      transmission curves at test points across lens surfaces to determine optical
      properties based on the Beer-Lambert law. Factors determining the transmission
      curves include the hydrogel lens used, its refractive index, whether a UV
      radiation-blocking dopant is incorporated, the water content, and the thickness
      of the lens. Test lenses of equal power were placed over a detecting fiber optic
      and illuminated by a deuterium source, and transmission spectra were recorded.
      The small optical sampling size allowed the spectral transmission profile to be
      determined across the lens surface, and comparisons were made with different
      lenses. RESULTS: Transmission curves across the lenses showed greater UV
      radiation-blocking capacity at the thicker peripheral region, with the 50% cutoff
      wavelength moving toward the visible spectrum by 10 nm from the center to the
      periphery. In addition, the ability to determine the spatially specific
      absorption coefficient and the related UV radiation protection factor was
      demonstrated. CONCLUSIONS: The system measures spatial variation in lens
      transmission and comparing different lens types while overcoming many of the
      handling limitations of cuvette-based spectrophotometer methods. The data show
      good agreement with published transmission curves and allow intralens and
      interlens comparisons.

PMID- 17496697
TI  - Contact lens-induced infectious keratitis in Japan.
AB  - PURPOSE: To identify microbiologic characteristics of infectious keratitis
      associated with contact lenses. METHODS: The authors retrospectively examined the
      microorganism isolated from patients with microbial corneal ulcer associated with
      contact lenses during a 5-year period. Herpetic and other viral infections were
      excluded from this study. Patient age, sex, type of contact lens, and isolated
      organisms were collected from medical records. RESULTS: Sixty-seven eyes of 66
      patients (54.5%) who possibly had contact lens-induced infectious keratitis were
      reviewed. Cultures of corneal scrapings or eye discharge were positive in 30
      (44.8%) of 67 eyes. A total of 35 strains of bacteria were detected, among which
      there were 29 (82.9%) gram-positive bacteria, two (5.7%) gram-negative bacteria,
      three (8.6%) fungi, and one (2.9%) species of Acanthamoeba. The most common type
      of contact lens was a conventional soft contact lens (25 eyes, including extended
      wear in seven eyes), whereas hard contact lenses, including rigid gas-permeable
      contact lenses, were worn in 19 eyes. In addition, frequent-replacement lenses
      were used in 17 eyes, whereas weekly lenses and daily lenses were used for three
      eyes each. The largest age group was the 20s for all types of lenses.
      CONCLUSIONS: The results of isolation and culture are essential for improving the
      cure rate, especially for patients who have severe corneal ulcers.

PMID- 17496698
TI  - Trends in microbial keratitis in Japan.
AB  - PURPOSE: To identify microbiologic characteristics of infectious keratitis and
      predisposing factors. METHODS: The microorganisms isolated from patients with
      infectious corneal ulcers during the 5 years between January 1999 and December
      2003 were retrospectively examined. Herpetic and other viral infections were
      excluded from this study. Patient age, sex, risk factors, and isolated organisms
      were collected. RESULTS: In 123 eyes of 122 patients, organisms were isolated
      from 72 (58.5%) eyes. In total, 99 different organisms were isolated. Among
      these, 77 (77.8%) were gram-positive bacteria; 18 (18.2%) were gram-negative
      bacteria; six (6.1%) were fungi; and one (1.0%) was acanthamoeba. Contact lens
      wear was the main risk factor (54.5%), and ocular surface disease and previous
      ocular surgery were present in 20.5% and 13.1% of cases, respectively.
      Posttreatment visual acuity was significantly improved by pretreatment in culture
      positive groups treated according to the antibiotic susceptibilities (Wilcoxon t
      test, P<0.01). CONCLUSIONS: The results are changing to those reported by other
      countries and generations. Contact lens wear is the most important risk factor in
      Japan. The results of isolation and culture are essential for improving the cure
      rate.

PMID- 17496699
TI  - Long-term clinical results: 3 years of up to 30-night continuous wear of
      lotrafilcon A silicone hydrogel and daily wear of low-Dk/t hydrogel lenses.
AB  - PURPOSE: To summarize results of a 3-year clinical trial assessing subjective and
      objective experience with lotrafilcon A silicone hydrogel (SH) lenses for up to
      30 nights of continuous wear or low-Dk/t daily-wear (LDW) hydrogel lenses.
      METHODS: Nineteen sites dispensed SH lenses to 317 subjects (286 current wearers
      and 31 new wearers) and 2-week replacement LDW lenses to 81 new wearers in a 3
      year study. RESULTS: For the SH cohort, limbal redness, conjunctival redness, and
      corneal neovascularization improved among 23%, 21%, and 13% of eyes, respectively
      (P<0.001), with no signs increasing significantly. For the LDW cohort, limbal
      redness, papillary conjunctivitis, and corneal staining increased among 11%, 21%,
      and 13% of eyes, respectively (P<0.02), with no signs improving significantly.
      The change in average spherical equivalent power was -0.03 diopters for the age
      matched SH cohort and -0.40 diopters for the LDW cohort (P=0.007). During the 3
      years, the SH group reported significantly less frequent dryness during and at
      the end of the day, redness, photophobia, lens awareness, and blurred vision.
      Significantly more LDW lens wearers reported frequent during-the-day and end-of
      day dryness and blurred vision. CONCLUSIONS: During the 3 years, lotrafilcon A
      lens wearers who wore their lenses continuously for up to 30 nights showed
      stable, long-term improvements in many signs of corneal health and symptoms along
      with less myopic progression versus daily wearers of low-Dk/t hydrogel lenses.
      Many biomicroscopy signs and symptoms worsened among neophytes wearing daily-wear
      low-Dk/t hydrogel lenses. The use of lotrafilcon A lenses may minimize many
      ocular changes from soft contact lens wear.

PMID- 17496700
TI  - Contact lens fitting profile in Portugal in 2005: strategies for first fits and
      refits.
AB  - PURPOSE: To evaluate the standards of contact lens practice in Portugal, with
      particular attention paid to the characteristics of first fits and refits
      regarding aspects such as symptoms of dryness, overnight wear, silicone hydrogel
      and multifocal prescriptions, and care systems. METHODS: A questionnaire was
      distributed to 300 contact lens practitioners in Portugal, and they were asked to
      complete them with the following first 10 fittings (only right eye of each
      patient). Fifty-six questionnaires were returned to total 529 fittings. RESULTS:
      The mean age of contact lens wearers was 28.1 +/- 10.1 years, and 94.4% of the
      wearers were fitted with soft contact lenses (67.9% hydrogel lenses, 21.2%
      silicone hydrogel lenses, and 5.2% biomimetic soft contact lenses). Sixty percent
      of patients wore their contact lenses for 9 to 12 hours per day. The lenses were
      replaced on a monthly basis in 71% of cases, and 82.8% of wearers used a
      multipurpose solution for lens cleaning and disinfection. Significant differences
      were found between first fits and refits regarding the prevalence of dryness
      symptoms (higher incidence of frequent symptoms in the evening in the refitting
      group, P<0.01, chi2), replacement schedule (lower incidence of monthly disposable
      lenses in refits compared to first fits, P<0.05, chi2), and care regimen (lower
      incidence of multipurpose solutions and higher incidence of hydrogen peroxide in
      refits, P<0.01, chi2). CONCLUSIONS: Statistical analysis of the current trends in
      the Portuguese contact lens fitting profile showed that contact lens
      practitioners in Portugal are receptive to use innovations in contact lens
      products, such as silicone hydrogel and biomimetic materials, and daily
      disposable contact lenses to refit patients who have not succeeded with previous
      lenses. Multifocal lenses also experienced a significant increase in their
      prevalence among refits and new fits. Rigid gas-permeable materials maintained
      and even experienced a slight increase in refits. Conversely, there is still a
      low incidence of extended-wear prescriptions, most of them being made with low-Dk
      soft contact lenses.

PMID- 17496701
TI  - Insertion of a bandage contact lens with Minims.
AB  - PURPOSE: To describe a new technique for the insertion of a bandage contact lens
      with the help of sterile Minims. METHODS: The bandage contact lens is picked up
      with the nozzle of the Minims by suction. The lens is then taken to the patient,
      placed on the cornea, and released by breaking the vacuum. RESULTS: Examination
      of the contact lens under the microscope after insertion showed no damage.
      CONCLUSIONS: Insertion of a bandage contact lens with Minims is a nontouch,
      inexpensive, easy, and patient-friendly method. It can reduce the risk of
      infection in already compromised eyes.

PMID- 17496702
TI  - External factors affecting data acquisition during corneal topography
      examination.
AB  - PURPOSE: To analyze the factors affecting data acquisition during corneal
      topography examination with the Medmont E-300 videokeratoscope and to provide
      strategies to minimize their effects. METHODS: Sixty eyes from thirty young
      adults were examined. A second observer registered incidences with the potential
      to affect data acquisition. Those factors were correlated with the difficulty of
      measurements as judged subjectively by the practitioner who performed the
      examination. Measurements of axial curvature were analyzed to evaluate the
      variability expressed as intrasession and intersession coefficient of variation
      and the standard error of the mean (SEM). RESULTS: The level of difficulty rated
      by the practitioner was in general low, with 70% of the eyes being easy or very
      easy to measure. For the remaining 30% of the eyes, corneal topography
      measurements were considered to be difficult (27%) or very difficult (3%). Of the
      external parameters investigated, only fixation instability (P<0.001, chi2) and
      the need for head repositioning (P=0.024, chi2) were associated significantly
      with a higher level of difficulty, as rated subjectively by the practitioner.
      Further analysis showed that some external factors, including those previously
      mentioned and others related to tear instability, affect the variability of
      measurements at certain corneal locations, particularly in the vertical meridian
      when related to tear instability and in the horizontal meridian when related to
      the need for head repositioning on the chin rest owing to physiognomy
      interferences with the keratoscope cone. Intersession SEM improved when three
      readings from each session were considered. CONCLUSIONS: The level of subjective
      difficulty found during videokeratoscopy examination is correlated strongly with
      fixation instability and the need for head reorientation in the chin rest,
      whereas tear-related events seem to be less relevant in the practitioner
      perception of test ease or difficulty. Those factors have relevance in
      measurement variability.

PMID- 17496703
TI  - Contrast visual acuity with bifocal contact lenses.
AB  - PURPOSE: To compare the quality of vision of a bifocal rigid gas-permeable
      contact lens versus a bifocal soft contact lens in subjects with presbyopia.
      METHODS: Sixteen healthy presbyopic subjects with no ocular disease but
      experienced with contact lens wear were enrolled in the study. Subjects randomly
      wore both types of bifocal lenses for 30 minutes with a washout period of 30
      minutes each in a crossover manner. The primary outcome measure was the
      difference in contrast visual acuity. Distance and near contrast visual acuities
      with the two bifocal lens types were measured in different lighting environments
      and at multiple contrast levels. After the measurement, subjects were asked to
      rate their subjective vision by using the four categories with both lens types
      throughout the study. At the end of the study, subjects were also asked which of
      the two lens types they preferred. RESULTS: Under photopic conditions, distance
      and near visual acuities decreased at the 25% and 10% contrast levels,
      respectively, in subjects wearing bifocal soft contact lenses (P<0.05). Under
      scotopic conditions, distance visual acuity decreased at the 5% contrast level
      with the bifocal rigid gas-permeable contact lenses (P<0.05). For subjective
      responses of clarity, there were no differences between lens types for distance
      vision (P>0.05), but bifocal rigid gas-permeable lenses were clearer than bifocal
      soft contact lenses for near vision (P<0.05). CONCLUSIONS: Bifocal rigid gas
      permeable contact lenses showed better visual performance than bifocal soft
      contact lenses did.

PMID- 17496704
TI  - A retrospective case series: use of SoftPerm contact lenses in patients with
      keratoconus.
AB  - PURPOSE: To evaluate the performance of the SoftPerm contact lens in patients
      with irregular astigmatism caused by keratoconus. METHODS: Twenty-four eyes of 14
      patients with keratoconus who had intolerance to rigid gas-permeable contact
      lenses and were fitted with SoftPerm lenses at Kartal Training and Research
      Hospital between August 1998 and January 2002 were evaluated retrospectively. The
      average follow-up time was 23 months. Patients were between the ages of 16 and 39
      years. All patients were examined by corneal topography before a SoftPerm contact
      lens trial. A standard protocol was used to select the initial trial lens on the
      basis of computer-generated topographic keratometric readings. Final lens
      selection was based on clinical performance. Visual acuity and complications were
      analyzed after fitting. RESULTS: Best-corrected spectacle visual acuity of 20/40
      or better was noted in 12.5% of eyes before the SoftPerm contact lens trial and
      increased to 83.3% after the SoftPerm contact lens fitting. Lens damage
      especially related to separation at the junction was observed in 29.1% of
      patients, discomfort in 29.1%, giant papillary conjunctivitis in 25%, and
      peripheral corneal neovascularization in 25%. Discomfort was the most common
      reason for discontinuation. CONCLUSIONS: SoftPerm lenses can be considered when
      high astigmatism is encountered in patients with keratoconus who have better
      visual acuity with SoftPerm lenses than with spectacles and who are intolerant of
      rigid gas-permeable lenses.

PMID- 17496705
TI  - Corneal nerve structure and function in keratoconus: a case report.
AB  - PURPOSE: To investigate corneal nerve structure and function in a 24-year-old
      patient with keratoconus and prominent corneal nerves. METHODS: Corneal nerve
      appearance was assessed by using a corneal confocal microscope, and corneal nerve
      function was assessed by using a Cochet-Bonnet aesthesiometer. Findings were
      compared to those of an age-matched control subject without keratoconus. RESULTS:
      The patient with keratoconus was found to have thicker nerve fiber bundles in the
      stroma (keratoconus vs. control, 9.8 +/- 5.0 microm vs. 5.4 +/- 2.7 microm) and
      reduced nerve fiber density in the subepithelial plexus (keratoconus vs. control,
      269.7 +/- 145.6 microm vs. 1,258 +/- 254.8 mum) compared to the control subject.
      The patient with keratoconus was found to have reduced corneal sensitivity
      compared to the control subject (keratoconus vs. control 0.39 gr/mm2 vs. 1.59
      gr/mm2). CONCLUSIONS: Corneal confocal microscopy proved to be a useful in vivo
      technique for assessing corneal nerve structure in this patient with keratoconus.
      Although the total number of stromal nerve fiber bundles was reduced in the
      patient with keratoconus versus the control subject, the increased tortuosity and
      increased nerve fiber diameter may explain why the corneal nerves appear more
      visible in this patient with keratoconus.

PMID- 17496706
TI  - Microbial keratitis in keratoglobus-associated vernal keratoconjunctivitis and
      atopic dermatitis.
AB  - PURPOSE: The authors describe a patient with keratoglobus and a history of vernal
      keratoconjunctivitis and atopic dermatitis who acutely developed corneal hydrops
      and severe microbial keratitis. The infectious keratitis responded poorly to
      medical management and resulted in enucleation of the eye. METHODS: A 25-year-old
      man presented with an acutely painful, red left eye. He had an ocular history of
      keratoglobus in association with vernal keratoconjunctivitis and atopic
      dermatitis. His visual acuity was light perception in the left eye and 20/40 in
      the right eye. Ocular examination showed a grossly edematous cornea with breaks
      in Descemet's membrane, a central infiltrative ulcer, and hypopyon. RESULTS:
      Corneal scrapings showed gram-positive beta-hemolytic streptococci, for which
      topical treatment of ceftazidime and benzylpenicillin every 30 minutes by day and
      night was commenced with an oral course of ciprofloxacin 750 mg twice a day.
      Despite aggressive therapy, the microbial keratitis progressed, and the hypopyon
      increased in size. The patient subsequently underwent enucleation of his left
      eye. CONCLUSIONS: This is the first reported case of microbial keratitis with
      corneal hydrops in a patient with keratoglobus, vernal keratoconjunctivitis, and
      atopic dermatitis. His ocular and dermatologic comorbidity may have impaired
      corneal integrity and allowed penetration of organisms, resulting in a severe
      case of keratitis that responded poorly to medical management.

PMID- 17496707
TI  - Role of mini-scleral gas-permeable lenses in the treatment of corneal disorders.
AB  - PURPOSE: Case report on the clinical implications of mini-scleral gas-permeable
      contact lenses in the treatment of corneal disorders. METHODS: Three patients
      with different corneal disorders were fitted with Jupiter design mini-scleral gas
      permeable contact lenses. RESULTS: All three patients achieved excellent vision
      and comfort. The contact lenses were tolerated well, and no complications were
      observed. CONCLUSIONS: Mini-scleral gas-permeable contact lenses provide a good
      option for patients who require gas-permeable contact lenses for optimal visual
      function but do not tolerate corneal contact lenses. Mini-scleral lenses are also
      an excellent therapeutic tool in the treatment of at least some forms of severe
      dry eyes.

PMID- 17496708
TI  - Why rescue the administrative data version of the "failure to rescue" quality
      indicator.

PMID- 17496709
TI  - Finally present on admission but needs attention.

PMID- 17496710
TI  - Failure to rescue: validation of an algorithm using administrative data.
AB  - BACKGROUND: Failure to rescue (FTR), the rate of death in patients suffering 1 of
      6 in-hospital complications, is an Agency for Healthcare Research and Quality
      (AHRQ) Patient Safety Indicator calculated from administrative data. OBJECTIVE: :
      We sought to assess the accuracy of the AHRQ FTR algorithm. METHODS: We undertook
      a retrospective chart review of 60 denominator cases of FTR identified by the
      algorithm at each of 40 University HealthSystem Consortium institutions. The
      primary outcome was the overall accuracy of the algorithm compared with chart
      review. We also assessed accuracy by complication type, patient characteristics,
      institution, service assignment, and mortality. RESULTS: Of 2354 cases, 1193
      (50.7%) were accurately identified by the algorithm as having had at least one of
      the FTR-qualifying complications during hospitalization. Of the 3073
      complications identified in these patients, 1497 (48.7%) were correctly flagged
      by the algorithm, 907 (29.5%) were present on admission, 419 (13.6%) were not
      confirmed by chart review, and 250 (8.1%) met a predefined complication-specific
      criterion for exclusion. The case accuracy rate varied significantly by
      institution (mean, 50.7%; range, 18.3-100%; P < 0.001), service assignment
      (surgical service, 62.9% vs. nonsurgical service, 42.9%; P < 0.001), and
      mortality (alive, 43.9% vs. dead, 67.5%; P < 0.001) but was not affected by
      patients' age, gender, race, or insurance status. CONCLUSIONS: As currently
      calculated from administrative data, the FTR algorithm misidentifies half of the
      cases on average, is least accurate for nonsurgical cases, and is widely variable
      across institutions. This indicator may be useful internally to flag possible
      cases of quality failure but has limitations for external institutional
      comparisons. Improvements in coding quality and consistency across institutions
      are needed.

PMID- 17496711
TI  - Modifying DRG-PPS to include only diagnoses present on admission: financial
      implications and challenges.
AB  - OBJECTIVE: The inability to distinguish complications acquired in hospital from
      comorbid conditions that are present on admission (POA) has long hampered the use
      of claims data in quality and safety research. Now pay-for-performance
      initiatives and legislation requiring Medicare to reduce payment for acquired
      infections add imperative for POA coding. This study used data from 2 states
      currently coding POA to assess the financial impact if Medicare pays based on POA
      conditions only and to examine the challenges in implementing POA coding.
      METHODS: Medicare payments were calculated based first on all diagnoses and then
      on POA diagnoses in the Medicare discharge abstracts from California and New York
      in 2003, using the Diagnosis Related Group (DRG)-based Prospective Payment System
      (PPS) formula. The potential savings that result from excluding non-POA diagnoses
      were calculated. Patterns of POA coding were explored. RESULTS: Medicare could
      have saved $56 million in California, $51 million in New York, and $800 million
      nationwide in 2003 had it paid hospital claims based only on POA diagnoses.
      Approximately 15% of the claims had non-POA codes, but only 1.4% of the claims
      were reassigned to lower-cost DRGs after excluding non-POA diagnoses. Excluding
      non-POA diagnoses resulted in reduced payment for operating costs, but increased
      outlier payments because some of the claims were designated as "unusually high
      cost" in the lower-cost DRGs. POA coding patterns suggest some problems in
      current POA coding. CONCLUSIONS: To be consistent with pay-for-performance
      principles and make claims data more useful for quality assurance, incorporating
      POA coding into DRG-PPS could produce sizable savings for Medicare.

PMID- 17496712
TI  - Use of a matching algorithm to evaluate hospital coronary artery bypass grafting
      performance as an alternative to conventional risk adjustment.
AB  - BACKGROUND: Although public reporting of hospital and physician performance is a
      cornerstone of the effort to improve health care quality, the optimal approach to
      risk adjustment is unknown. OBJECTIVE: We sought to assess hospital quality using
      a matching algorithm based on a generalized distance metric and to compare this
      approach to the more traditional regression-based approach. DESIGN/ DATA SOURCE:
      This was a retrospective study using the New York State (NYS) Coronary Artery
      Bypass Surgery Reporting System (CSRS), focusing on all patients undergoing
      isolated CABG surgery in NYS who were discharged in 1999 (18,116 patients).
      Patients from specific hospital were matched to a control group using the
      Mahalanobis distance. The hospitals' expected mortality rate was calculated in 2
      ways: (1) as the mortality rate of the control group or (2) as the mortality rate
      predicted by the NYS CABG model. Hospitals whose observed mortality rate was
      significantly different from their expected mortality rate (OE difference) were
      defined as quality outliers. RESULTS: The 2 risk-adjustment methodologies
      disagreed on the outlier status of 4 of the 33 hospitals. Kappa analysis
      demonstrated substantial agreement between these 2 methods for identifying
      quality outliers: kappa = 0.61. There was excellent agreement between the point
      estimates of the OE difference obtained using these 2 risk adjustment
      methodologies. CONCLUSION: Basing outcome assessment on either matching or
      regression modeling yielded similar findings on hospital ranking but only
      moderate level of agreement on hospital quality. The use of matching may enhance
      the transparency and acceptance of outcome report cards by hospitals and
      physicians.

PMID- 17496713
TI  - Hospital episodes and physician visits: the concordance between self-reports and
      medicare claims.
AB  - BACKGROUND: Health services use typically is examined using either self-reports
      or administrative data, but the concordance between the 2 is not well
      established. OBJECTIVE: We evaluated the concordance of hospital and physician
      utilization data from self-reports and claims data, and identified factors
      associated with disagreement. METHODS: We performed a secondary analysis on
      linked observational and administrative data. A national sample of 4310
      respondents who were 70 years old or older at their baseline interviews was used.
      Self-reported and Medicare claims-based hospital episodes and physician visits
      for 12 months before baseline were examined. Kappa statistics were used to
      evaluate concordance, and multivariable multinomial logistic regression was used
      to identify factors associated with overreporting (self-reports > claims),
      underreporting (self-reports < claims), and concordant-reporting (self-reports
      approximately claims). RESULTS: The concordance of hospital episodes was high
      (kappa = 0.767 for the 2 x 2 comparison of none vs. some and kappa = 0.671 for
      the 6 x 6 comparison of none, 1, ..., 4, or 5 or more), but concordance for
      physician visits was low (kappa = 0.255 for the 2 x 2 comparison of none versus
      some and kappa = 0.351 for the 14 x 14 comparison of none, 1, ..., 12, and 13 or
      more). Multivariable multinomial logistic regression indicated that over-, under
      , and concordant-reporting of hospital episodes was significantly associated with
      gender, alcohol consumption, arthritis, cancer, heart disease, psychologic
      problems, lower body functional limitations, self-rated health, and depressive
      symptoms. Over-, under-, and concordant-reporting of physician visits were
      significantly associated with age, gender, race, living alone, veteran status,
      private health insurance, arthritis, cancer, diabetes, hypertension, heart
      disease, lower body functional limitations, and poor memory. CONCLUSIONS:
      Concordance between self-reported and claims-based hospital episodes was high,
      but concordance for physician visits was low. Factors significantly associated
      with bidirectional (over- and underreporting) and unidirectional (over- or
      underreporting) error patterns were detected. Therefore, caution is advised when
      drawing conclusions based on just one physician visit data source.

PMID- 17496714
TI  - Short-term statin exposure is associated with reduced all-cause mortality in
      persons with diabetes.
AB  - BACKGROUND: The survival benefit of statins in nontrial populations of persons
      with diabetes is unknown. OBJECTIVE: : We sought to determine all-cause mortality
      in fiscal year 2001 (FY01) after statin initiation in FY 99 and/or FY00 in
      individuals with diabetes in the Veterans Healthcare Administration (VHA).
      METHODS: Using a retrospective longitudinal cohort analysis, we analyzed 201,102
      veterans with diabetes from 104 VHA facilities with medical, pharmacy, and
      laboratory information from VHA and Medicare databases. Patients with statin
      exposure, defined as having medication possession coverage >50% of eligible days
      in FY99 and/or FY00, were characterized as initiators if no statin prescription
      was found in FY98. Otherwise, they were characterized as continuing users. We
      defined 4 statin exposure groups: FY99 only, FY00 only, both FY99 and 00, and
      neither year. All-cause mortality was determined in FY01. Propensity score
      matched comparisons were used to corroborate results from mixed effects logistic
      models. RESULTS: FY01 mortality was no different between FY99-only initiators and
      the nonexposure group (odds ratio [OR] = 1.08, P = 0.429). In contrast, FY00-only
      and FY99-00 initiator groups showed odds ratio of 0.75 (P < 0.0001) and 0.71 (P <
      0.0001), respectively. There was a similar benefit for continuing users.
      Propensity analysis demonstrated consistent findings. Increased statin adherence
      from >50% to >75% was associated with increased benefit (OR = 0.71, P < 0.0001
      versus OR = 0.62, P = 0.0002). CONCLUSIONS: One to 2-year statin exposure is
      associated with a 25% to 29% risk reduction in all-cause mortality of the
      subsequent year in a high-risk diabetes cohort.

PMID- 17496715
TI  - Predicted quality-adjusted life years as a composite measure of the clinical
      value of diabetes risk factor control.
AB  - BACKGROUND: Control of blood pressure, low-density lipoprotein cholesterol (LDL
      c), and A1c can lower the risk for diabetes complications. These quality
      indicators often are examined separately and weighted equally in performance
      measurement, potentially discarding important information. OBJECTIVES: We sought
      to create a composite indicator of the clinical benefit, or value, of diabetes
      risk factor control that appropriately weights the clinical importance of A1c,
      LDL-c, and blood pressure, and to test its usability for quality measurement.
      METHODS: The combined value of control for 3 diabetes risk factors, measured by
      predicted quality-adjusted life years (QALYs), was compared in diabetes patients
      (n = 129,236 in 2001; n = 185,006 in 2003) in Kaiser Permanente Northern
      California across 16 medical center populations in 2001 and 2003 using
      hierarchical linear regression to adjust for case-mix differences. Patient-level
      QALYs, simulated from risk factor and case-mix variables in a Markov model, was
      the main outcome variable. RESULTS: There was significant cross-sectional
      variability in average case-mix adjusted QALYs for diabetes patients across
      centers in 2003. QALYs increased from 2001 to 2003 as the result of improved risk
      factor control; longitudinal improvements in QALYs also showed variation across
      centers. Regression analyses demonstrated the greater impact of blood pressure
      versus LDL-c or A1c control on QALYs, and the greater value of risk factor
      control in those with poor versus near or in-control blood pressure. CONCLUSION:
      Using predicted QALYs to measure value holds promise as a sensitive composite
      indicator for quality measurement. Complex, evidence-based quality indicators
      such as these can potentially provide accurate and useful information to health
      plans, providers, and consumers.

PMID- 17496716
TI  - Trends in obesity-related counseling in primary care: 1995-2004.
AB  - OBJECTIVE: We sought to ascertain whether the percentage of visits in which
      physicians provided obesity-related counseling services increased between 1995
      and 2004. METHOD: Data came from the 1995 to 2004 National Ambulatory Medical
      Care Survey, an annual national survey of visits to office-based physicians.
      Analyses are restricted to visits by adults to a primary care physician (PCP;
      general/family or internal medicine). The main outcome measure is the percentage
      of visits to physicians where patients were counseled about exercise,
      diet/nutrition or weight loss. RESULTS: Sample sizes ranged from 9,583 to 14,071.
      In 2003/2004, approximately 20% of visits to PCPs included counseling for
      diet/nutrition, 14% for exercise, and 6% for weight loss. Approximately 24% of
      visits included at least one of these types of counseling. The odds of receiving
      counseling for any of these services were 22% lower in 2001/2002 and 18% lower in
      2003/2004 compared with 1995/1996. Patients who went to the doctor for weight
      related concerns or with an obesity-related diagnosis were more likely to receive
      counseling than the general population. Longer visits were associated with
      greater probability of obesity-related counseling. CONCLUSIONS: Obesity-related
      counseling does not appear to be a substantial part of the services provided by
      physicians. Further efforts in developing interventions that can be used by
      physicians and demonstrating their effectiveness within clinical practice are
      needed.

PMID- 17496717
TI  - Medical specialists' patient-centered communication and patient-reported
      outcomes.
AB  - BACKGROUND: Physicians' patient-centered communication in the medical
      consultation is generally expected to improve patient outcomes. However,
      empirical evidence is contradictory so far, and most studies were done in primary
      care. OBJECTIVE: We sought to determine the association of specialists' patient
      centered communication with patient satisfaction, adherence, and health status.
      METHODS: Residents and specialists in internal medicine (n = 30) and their
      patients (n = 323) completed a questionnaire before a (videotaped) follow-up
      encounter. Patients' satisfaction was assessed immediately after the consultation
      and their self-reported treatment adherence, symptoms, and distress 2 weeks
      later. Specialists' patient-centered communication was assessed by coding
      behaviors that facilitate or rather inhibit patients to express their
      perspective. Patient participation was assessed by determining their relative
      contribution to the conversation and their active participation behavior.
      Outcomes were assessed using standard questionnaires. Analyses accounted for
      relevant patient, visit and physician characteristics. RESULTS AND CONCLUSIONS:
      Medical specialists' facilitating behavior was associated with greater
      satisfaction in patients who were less confident in communicating with their
      doctor. Patient-centered communication was not associated with patients' health
      status or adherence in general, but facilitating behavior was positively related
      to the adherence of patients with a foreign primary language. In general,
      patients appeared to be more satisfied after an encounter with a more
      facilitating and a less-inhibiting physician, but these associations diminished
      when controlling for background characteristics. We conclude that the absence of
      strong associations between patient-centered communication and patient-reported
      outcomes may be explained by medical specialists being responsive to patients'
      characteristics.

PMID- 17496718
TI  - Communication interventions make a difference in conversations between physicians
      and patients: a systematic review of the evidence.
AB  - OBJECTIVE: We sought to synthesize the findings of studies examining
      interventions to enhance the communication behaviors of physicians and patients
      during outpatient encounters. METHODS: We conducted searches of 6 databases
      between 1966 and 2005 to identify studies for a systematic review and synthesis
      of the literature. Eligible studies tested a communication intervention; were
      randomized controlled trials (RCTs); objectively assessed verbal communication
      behaviors as the primary outcome; and were published in English. Interventions
      were characterized by type (eg, information, modeling, feedback, practice),
      delivery strategy, and overall intensity. We abstracted information on the
      effects of the interventions on communication outcomes (eg, interpersonal and
      information exchanging behaviors). We examined the effectiveness of the
      interventions in improving the communication behaviors of physicians and
      patients. RESULTS: Thirty-six studies were reviewed: 18 involved physicians; 15
      patients; and 3 both. Of the physician interventions, 76% included 3 or 4 types,
      often in the form of practice and feedback sessions. Among the patient
      interventions, 33% involved 1 type, and nearly all were delivered in the waiting
      room. Intervention physicians were more likely than controls to receive higher
      ratings of their overall communication style and to exhibit specific patient
      centered communication behaviors. Intervention patients obtained more information
      from physicians and exhibited greater involvement during the visit than controls.
      CONCLUSIONS: The interventions were associated with improved physician and
      patient communication behaviors. The challenge for future research is to design
      effective patient and physician interventions that can be integrated into
      practice.

PMID- 17496719
TI  - Adoption of system strategies for tobacco cessation by state medicaid programs.
AB  - BACKGROUND: The Public Health Service's Clinical Practice Guideline for treating
      tobacco dependence recommends 6 system-wide strategies for health administrators,
      insurers, and purchasers to support tobacco cessation. METHODS: A 24-question
      survey was sent to each state Medicaid program office in the fall of 2005,
      including questions to assess whether each state Medicaid program adopted 4 of
      the 6 system strategies most relevant to Medicaid contracting. RESULTS: The
      number of system strategies adopted by state Medicaid programs in 2005 ranged
      from 0 to 4 of the 4 strategies examined. Oregon, Pennsylvania, and West Virginia
      adopted all 4 systems strategies for cessation in their Medicaid programs. Seven
      states adopted 3 strategies, and 14 states adopted 2. Seventeen states adopted
      only 1 of the system strategies, and 10 state Medicaid programs had not adopted
      any of the recommended system strategies for tobacco cessation. The most
      frequently adopted strategy was Medicaid coverage for tobacco dependence
      treatments, with 75% of the states covering at least 1 recommended treatment
      under their Medicaid program. CONCLUSIONS: Although most state Medicaid programs
      have made efforts to adopt at least one of the recommended system strategies to
      support tobacco cessation, there remains substantial room for improvement. More
      research is needed regarding the barriers to Medicaid program adoption of
      comprehensive system strategies to promote cessation among their enrolled
      populations.

PMID- 17496720
TI  - Depression-free day to utility-weighted score: is it valid?
AB  - BACKGROUND: Cost-utility analyses using formulas to convert depression-free days
      (DFDs) to utility-weighted scores are increasingly common. These formulas are
      based on linear extrapolation of data documenting the correlation between
      depression symptom severity and generic health-related quality of life.
      OBJECTIVE: We sought to examine the validity of formulas converting DFDs to
      utility weights. METHODS: We undertook an observational study with data
      collection at baseline, 1 week and 1, 3, 6, 9, and 12 months on 77 subjects (42
      inpatient, 35 outpatient) diagnosed with current major depression. Subjects were
      divided into treatment response categories based on changes in depression
      severity. Depression severity measures used were the Hamilton Rating Scale for
      Depression (HAM-17) and Beck Depression Inventory (BDI) and the health-related
      quality of life measure was the self-administered Quality of Well-Being scale
      (QWB-SA). DFD calculations were based on depression severity scores and converted
      to utility weights using available formulas. Utility-weighted data collected over
      the course of 1 year were used to estimate quality-adjusted life years (QALYs).
      RESULTS: QALYs estimated from the QWB-SA were significantly lower than those
      based on utility-weighted DFD calculations but the incremental QALYs were not
      significantly different. Using a slightly lower utility-weighted conversion
      factor for the BDI or a larger BDI severity range to calculate DFDs resulted in a
      better fit compared with the QWB-SA. CONCLUSIONS: Our results support the
      validity of the existing HAM-17 utility-weighted formula and suggest
      modifications for the BDI formula. If generic health-related quality of life
      measures are not available for conducting cost-utility analyses of depression
      interventions then the existing HAM-17 and modified BDI formulas appear to be
      reasonable alternatives.

PMID- 17496722
TI  - Molecular pathogenesis of Gilbert's syndrome: decreased TATA-binding protein
      binding affinity of UGT1A1 gene promoter.
AB  - OBJECTIVES: Gilbert's syndrome is a congenital, nonhemolytic, unconjugated
      hyperbilirubinemia. The most common genotype of Gilbert's syndrome is the
      homozygous polymorphism, A(TA)7TAA, in the promoter of the gene for UDP
      glucuronosyltransferase 1A1 (UGT1A1), with a thymine adenine insertion in the
      TATA-box-like sequence, which results in a decrease in UGT1A1 activity. The
      mechanism responsible for this decrease in UGT1A1 activity, however, has not been
      elucidated. To clarify the mechanism underlying this deficiency in UGT1A1
      activity in patients with Gilbert's syndrome. METHODS: The promoter activity
      assay using the wild-type A(TA)6TAA or the mutant A(TA)7TAA promoter and a
      luciferase reporter was performed in two different hepatoma cell lines. The
      binding affinity for a nuclear protein complex or for TATA-binding protein was
      evaluated by a competitive electophoretic mobility shift assay using wild-type or
      mutant TATA-box-like oligonucleotide probes and nuclear extract or TATA-binding
      protein. The formation of complexes between TATA-binding protein and wild-type or
      mutant oligonucleotide probes was also studied by a quantitive electophoretic
      mobility shift assay. RESULTS: A TA insertion in the TATA-box-like sequence of
      the promoter activity of UGT1A1 gene. A competitive electrophoretic mobility
      shift assay showed a decrease in nuclear protein complex binding affinity and
      TATA-binding protein binding affinity of the mutant TATA-box-like sequence
      A(TA)7TAA. When the mutants A(TA)5TAA and A(TA)8TAA were also compared,
      quantitative electrophoretic mobility shift assay demonstrated that the TATA
      binding protein binding affinity progressively decreased as the number of TA
      repeats in the TATA-box-like sequence increased. CONCLUSION: TA insertion in the
      TATA-box-like sequence of the UGT1A1 promoter affected its binding affinity for
      TATA-binding protein, causing a decrease in its activity. This explains the
      pathogenesis of Gilbert's syndrome.

PMID- 17496721
TI  - Adherence to antidepressant treatment among privately insured patients diagnosed
      with depression.
AB  - BACKGROUND: Antidepressants are effective in treatment of depression, but poor
      adherence to medication is a major obstacle to effective care. OBJECTIVE: We
      sought to describe patient and provider level factors associated with treatment
      adherence. METHODS: This was a retrospective, observational study using medical
      and pharmacy claims from a large health plan, for services provided between
      January 2003 and January 2005. We studied a total of 4312 subjects ages 18 or
      older who were continuously enrolled in the health plan with a new episode of
      major depression and who initiated antidepressant treatment. Treatment adherence
      was measured by using pharmacy refill records during the first 16 weeks (acute
      phase) and the 17-33 weeks after initiation of antidepressant therapy
      (continuation phase). Measures were based on Health Plan Employer Data and
      Information Set (HEDIS) quality measures for outpatient depression care. RESULTS:
      Fifty-one percent of patients were adherent through the acute phase; of those,
      42% remained adherent in the continuation phase. Receipt of follow-up care from a
      psychiatrist and higher general pharmacy utilization (excluding psychotropics)
      were associated with better adherence in both phases. Younger age, comorbid
      alcohol or other substance abuse, comorbid cardiovascular/metabolic conditions,
      use of older generation antidepressants, and residence in lower-income
      neighborhoods were associated with lower acute-phase adherence. Continuation
      phase adherence was lower for HMO participants than for others. CONCLUSION: In an
      insured population, many patients fall short of adherence to guideline
      recommended therapy for depression. Information from existing administrative data
      can be used to predict patients at highest risk of nonadherence, such as those
      with substance abuse, and to target interventions.

PMID- 17496723
TI  - Genomic and functional conservation of sedative-hypnotic targets in the
      zebrafish.
AB  - OBJECTIVES: The zebrafish is an ideally suited vertebrate animal model for large
      scale genetic screens and is emerging as a model organism in pharmacological and
      behavioral research. We investigated the effects of sedative hypnotics commonly
      used in humans on zebrafish locomotor activity and identified the corresponding
      genomic and receptor binding targets. METHODS: We studied radioreceptor binding
      and behavioral responses to compounds with known sedative hypnotic properties
      representing multiple pharmacological classes. These included GABAergic hypnotics
      such as benzodiazepines, barbiturates, and baclofen; alpha-2 adrenergic agonists;
      and histaminergic H1 antagonists. An automated system was used to quantify
      behavioral effects. Zebrafish homologs of histamine receptor H1, gamma-amino-n
      butyric acid type A (alpha-subunit), and gamma-amino-n-butyric acid type B (1 and
      2) receptor genes were identified through translating queries of the zebrafish
      Zv4 database with human receptor protein sequences. A pilot screen of 154 N-ethyl
      N-nitroso-urea-mutagenized F2 families was conducted with pentobarbital,
      flurazepam and mepyramine. RESULTS: Radioreceptor binding studies revealed high
      affinity binding sites for known gamma-amino-n-butyric acid type A, gamma-amino-n
      butyric acid type B, and histaminergic ligands. Drug immersion of 5-7-day-old
      larvae reduced mobility and, in some cases, produced a complete state of
      unresponsive immobility similar to anesthesia. These effects were dose-dependent
      and rapidly reversible in water. As established in mammals, (R)-baclofen was more
      active behaviorally and had higher affinity in binding studies when compared with
      (S)-baclofen. In this model, (S)-baclofen only partially reduced activity at high
      dose and blocked (R)-baclofen behavioral hypnotic effects. Genomic sequences with
      high similarity to the corresponding pharmacological targets were identified, but
      no mutants were found in the pilot screen. CONCLUSIONS: These results demonstrate
      conservation of gene, protein and function for many established sedative hypnotic
      pathways. The results indicate feasibility of conducting large-scale
      pharmacogenomic screens to isolate novel proteins modulating susceptibility to
      hypnotic compounds in a vertebrate system.

PMID- 17496724
TI  - Naturally occurring variations in the human 5-HT3A gene profoundly impact 5-HT3
      receptor function and expression.
AB  - BACKGROUND: The serotonin [5-hydroxytryptamine (5-HT)]-gated ion channel 5-HT3 is
      involved in the mediation of postoperative and radiotherapy/chemotherapy-induced
      nausea/emesis and in irritable bowel syndrome. It has also been suggested to play
      a role in various psychiatric diseases. Five naturally occurring single
      nucleotide polymorphisms leading to amino acid changes have been identified in
      the human 5-HT3A gene. METHODS AND RESULTS: We investigated the functional
      effects of these polymorphisms on the 5-HT3A receptor using fluorescence-based
      cellular assays. Notably, variants A33T, S253N, and M257I displayed 5-HT-induced
      maximal responses of 3-64% of the wild-type response, whereas R344H and P391R
      exhibited wild-type-like function. All variants displayed wild-type-like
      potencies of 5-HT and three 5-HT3 antagonists. Furthermore, all variants
      displayed Kd values similar to that of the wild-type receptor in a [H]GR65630
      binding assay. The surface expression of A33T, M257I, and R344H was reduced 2-4
      fold compared with the wild-type, despite similar total expression levels.
      Finally, coexpression of wild-type 5-HT3A or 5-HT3B subunits with 5-HT3A variants
      A33T, S253N, or M257I resulted in mixed or heteromeric receptors, characterized
      by significantly reduced maximal responses to 5-HT compared with the wild-type
      receptors. CONCLUSIONS: Three polymorphisms of the 5-HT3A gene gave rise to
      functionally impaired receptors whose function could not be rescued by either
      wild-type 5-HT3A or 5-HT3B. Three of the variant receptors were surface-expressed
      at reduced levels in spite of total expression levels similar to wild-type,
      indicating that these variants affect receptor biogenesis and/or trafficking.
      These severe single nucleotide polymorphism effects hold promise for
      identification of new 5-HT3A gene-disease causalities.

PMID- 17496725
TI  - Single nucleotide polymorphism discovery and haplotype analysis of Ca2+-dependent
      K+ channel beta-1 subunit.
AB  - The large-conductance, Ca-dependent K channel plays a key role in the control of
      vascular tone. Variation in the gene encoding the beta-1 subunit of the Ca
      dependent K channel (KCNMB1) has been reported to be associated with
      hypertension, however, variants in KCNMB1 have not been systematically
      characterized to date. In this study, we have performed the most comprehensive
      evaluation to date of single nucleotide polymorphisms in KCNMB1 using genomic DNA
      from 60 individuals of European, African and native American ancestry. We
      identified and characterized single nucleotide polymorphisms in the exons,
      intron/exon junctions, upstream region and 3' untranslated regions of KCNMB1
      using denaturing high-performance liquid chromatography combined with direct DNA
      sequencing. A total of 25 single nucleotide polymorphisms in KCNMB1 were
      identified. Seven of the polymorphisms (28%) are novel single nucleotide
      polymorphisms not reported previously. Allele frequencies range from less than
      1.7 to 50% and 19 single nucleotide polymorphisms had a minor allele frequency
      greater than 5%. A lack of strong linkage disequilibrium among the 25 single
      nucleotide polymorphisms was observed in all three race/ethnicity groups;
      therefore the identification of haplotype 'tag' single nucleotide polymorphisms
      for genetic association studies is not likely to be appropriate for KCNMB1.
      Multiple species comparative analysis and in-silico functional analysis were
      performed to identify potential functionally important single nucleotide
      polymorphisms within the gene. These data highlight that a tag single nucleotide
      polymorphism approach will not be appropriate for the study of genes such as
      KCNMB1, although potentially important functionally significant single nucleotide
      polymorphisms are suggested for future studies investigating the influence of
      this gene's variability on disease and drug response.

PMID- 17496726
TI  - Synergistic polymorphisms of beta1 and alpha2C-adrenergic receptors and the
      influence on left ventricular ejection fraction response to beta-blocker therapy
      in heart failure.
AB  - OBJECTIVES: The Arg389Gly polymorphism (Arg389Gly) in the beta1-adrenergic
      receptor gene (ADRB1) has been associated with improvement in left-ventricular
      remodeling with beta-blocker treatment. One study of risk for heart failure
      suggested a synergistic effect of ADRB1 Arg389Gly with the insertion/deletion
      polymorphism in the alpha2C-adrenergic receptor gene (ADRA2C). We tested whether
      the ADRA2C insertion/deletion polymorphism was associated with beta-blocker
      response in heart failure, either alone or in combination with the ADRB1Arg389Gly
      polymorphism. METHODS: Fifty-four beta-blocker naive heart failure patients
      underwent echocardiography before and after 5-6 months of metoprolol CR/XL
      therapy. Multivariant linear regression modeling was performed to assess the
      impact of genotypes and other variables on changes in left-ventricular function
      in response to metoprolol therapy. RESULTS: Deletion carriers had a significantly
      greater negative chronotropic response. Predictors of the end of study ejection
      fraction were baseline ejection fraction, deletion carrier status and Arg389Arg
      genotype. Patients with Arg389Arg/Del-carrier status showed the greatest ejection
      fraction increase with metoprolol CR/XL. Adjusting for baseline ejection
      fraction, final S-metoprolol plasma concentration and race, final ejection
      fraction in patients with this genotype combination was significantly higher than
      all other genotype combination groups. CONCLUSION: ADRB1 and ADRA2C polymorphisms
      synergistically influence the ejection fraction response to beta-blocker therapy
      of heart failure patients.

PMID- 17496727
TI  - A novel variant L263F in human inosine 5'-monophosphate dehydrogenase 2 is
      associated with diminished enzyme activity.
AB  - BACKGROUND AND OBJECTIVE: Inosine 5'-monophosphate dehydrogenase 2 is required
      for purine synthesis in activated lymphocytes. Variants in the IMPDH2 gene may
      account for the large inter-individual variability in baseline enzyme activity,
      immunosuppressive efficacy and side effects in transplant recipients receiving
      mycophenolic acid. Therefore, the objective of this study was to identify and
      functionally characterize IMPDH2 variants. METHODS: DNA samples from 152 solid
      organ transplant patients were screened at exons and exon/intron junctions of the
      IMPDH2 genes by PCR amplification followed by bidirectional direct DNA
      sequencing. Genetic variant was constructed by site-directed mutagenesis and
      transformed to an inosine 5'-monophosphate dehydrogenase-deficient strain of
      Escherichia coli h712. Proteins were purified to homogeneity and the enzymatic
      activity was measured by reduced nicotinamide adenine dinucleotide production.
      RESULTS: Nine genetic variants were identified in the IMPDH2 gene, with
      frequencies of the rarer alleles ranging from 0.5 to 10.2%. A novel nonsynonymous
      variant L263F was identified, and the kinetic assay demonstrated that the inosine
      5'-monophosphate dehydrogenase activity of L263F variant was decreased to 10% of
      the wild-type. The Ki for mycophenolic acid inhibition of the L263F variant was
      comparable with the wild-type, and the variant Km for inosine 5'-monophosphate
      and nicotinamide adenine dinucleotide did not change significantly. CONCLUSIONS:
      IMPDH2 has low genetic diversity, but the nonsynonymous variant L263F has a
      significant impact on inosine 5'-monophosphate dehydrogenase activity. This novel
      functional variant may be one of the factors contributing to the inter-individual
      difference of baseline inosine 5'-monophosphate dehydrogenase activity as well as
      drug efficacy and adverse events in transplant patients.

PMID- 17496728
TI  - Haplotype of growth hormone and angiotensin I-converting enzyme genes, serum
      angiotensin I-converting enzyme and ventricular growth: pathway inference in
      pharmacogenetics.
AB  - OBJECTIVES: An insertion/deletion (I/D) polymorphism in the angiotensin I
      converting enzyme (ACE) gene is associated with variations in circulating and
      tissue angiotensin I-converting enzyme activity, and differences in exercise
      induced left ventricular hypertrophic response. A genetic marker (CSH1.01) in the
      syntenic GH-CSH gene cluster correlates with metabolic syndrome in adult life in
      males. Approximately 24% linkage disequilibrium between CSH1.01T and D alleles of
      ACE I/D has also been reported. The objective was to examine the hypothesis that
      effects ascribed to ACE genotype may reflect causality in the GH-CSH cluster.
      METHODS: The ACE I/D polymorphism and GH-CSH BglII-B single nucleotide
      polymorphism (in strong linkage disequilibrium with CSH1.01) were determined in
      847 British Army recruits. Serum angiotensin I-converting enzyme activity and
      left ventricular mass were measured before and after a 12-week physical training
      program. Genotype and haplotype analyses of both markers were performed in
      relation to these phenotypes. RESULTS: The ACE I/D polymorphism was in linkage
      disequilibrium with BglII-B (D'=0.3). Strong association was seen between ACE I/D
      genotypes and serum angiotensin I-converting enzyme activity (P<0.0001), but not
      left ventricular mass change. BglII-B genotypes also associated significantly
      with serum angiotensin I-converting enzyme level (P<0.0001). Haplotype analysis,
      however, showed that most of this association resulted from linkage
      disequilibrium between BglII-B and ACE I/D. BglII-B did not associate with left
      ventricular mass change. CONCLUSIONS: GH-CSH BglII-B genotype associates
      significantly with angiotensin I-converting enzyme levels, but only through
      linkage disequilibrium with ACE I/D. Every phenotype with which ACE I/D has been
      associated merits investigation of potential causal effects originating in the GH
      CSH cluster (and vice versa), otherwise the chain of causality could be
      misinterpreted.

PMID- 17496729
TI  - Association between polymorphisms in prostanoid receptor genes and aspirin
      intolerant asthma.
AB  - BACKGROUND: Genetic predisposition is linked to the pathogenesis of aspirin
      intolerant asthma. Most candidate gene approaches have focused on leukotriene
      related pathways, whereas there have been relatively few studies evaluating the
      effects of polymorphisms in prostanoid receptor genes on the development of
      aspirin-intolerant asthma. Therefore, we investigated the potential association
      between prostanoid receptor gene polymorphisms and the aspirin-intolerant asthma
      phenotype. METHODS: We screened for genetic variations in the prostanoid receptor
      genes PTGER1, PTGER2, PTGER3, PTGER4, PTGDR, PTGIR, PTGFR, and TBXA2R using
      direct sequencing, and selected 32 tagging single nucleotide polymorphisms among
      the 77 polymorphisms with frequencies >0.02 based on linkage disequilibrium for
      genotyping. We compared the genotype distributions and allele frequencies of
      three participant groups (108 patients with aspirin-intolerant asthma, 93
      patients with aspirin-tolerant asthma, and 140 normal controls). RESULTS: Through
      association analyses studies of the 32 single nucleotide polymorphisms, the
      following single nucleotide polymorphisms were found to have significant
      associations with the aspirin-intolerant asthma phenotype: -616C>G (P=0.038) and 
      166G>A (P=0.023) in PTGER2; -1709T>A (P=0.043) in PTGER3; -1254A>G (P=0.018) in
      PTGER4; 1915T>C (P=0.015) in PTGIR; and -4684C>T (P=0.027), and 795T>C (P=0.032)
      in TBXA2R. In the haplotype analysis of each gene, the frequency of PTGIR ht3[G-G
      C-C], which includes 1915T>C, differed significantly between the aspirin
      intolerant asthma patients and aspirin-tolerant asthma patients (P=0.015).
      CONCLUSION: These findings suggest that genetic polymorphisms in PTGER2, PTGER3,
      PTGER4, PTGIR, and TBXA2R play important roles in the pathogenesis of aspirin
      intolerant asthma.

PMID- 17496730
TI  - Tumor necrosis factor-alpha inhibitor associated ulcerative colitis.
AB  - BACKGROUND: Flares or onset of inflammatory bowel disease in association with
      immunosuppression has been reported in the literature. METHODS: We studied 4
      cases of patients with rheumatic disease who developed or had a flare of
      ulcerative colitis either after initiation of or while taking a tumor necrosis
      factor-alpha inhibitor. RESULTS: We identified 4 patients, three male and one
      female. Two of the male patients had a seronegative spondyloarthropathy and one
      had rheumatoid arthritis. The female patient had amyopathic dermatomyositis. Two
      of the 4 patients had ulcerative colitis prior to tumor necrosis factor-alpha
      treatment. Both of these patients had quiescent ulcerative colitis that flared
      after they began taking etanercept. Two patients developed de novo ulcerative
      colitis while taking a tumor necrosis factor-alpha inhibitor. CONCLUSIONS: The
      data presented in these 4 cases supports a temporal relationship between
      initiating a tumor necrosis factor-alpha inhibitor and onset or flare of
      ulcerative colitis. These observations raise the possibility that tumor necrosis
      factor-alpha inhibitor therapy, which has been used as treatment for inflammatory
      bowel disease, may rarely be a factor in the development of disease.

PMID- 17496731
TI  - Hypoadiponectinemia in patients with cerebral infarction: comparison with other
      atherosclerotic disorders.
AB  - The present study was undertaken to determine serum adiponectin level in patients
      with cerebral infarction and to further analyze any difference in serum
      adiponectin levels among atherosclerotic disorders. One hundred fifty-two
      subjects with atherosclerotic disorders were enrolled, 110 males and 42 females,
      with the age of 67.0 +/- 9.9 years (mean +/- SD). They were divided into 62
      patients with cerebral infarction, 48 patients with ischemic heart disease, and
      42 patients with arteriosclerosis obliterans. Thirty-two subjects matched by age,
      gender, and body mass index served as controls. Serum adiponectin levels were 7.2
      +/- 0.6 microg/mL (mean +/- SE) in the patients with cerebral infarction, 7.2 +/-
      0.8 microg/mL in those with ischemic heart disease, and 6.9 +/- 0.9 microg/mL in
      those with arteriosclerosis obliterans. They were significantly less than the
      level of 12.6 +/- 1.9 microg/mL in the control group (P < 0.01). However, there
      was no difference in serum adiponectin level among three groups of
      atherosclerotic disorders. In the patients with acute cerebral infarction, serum
      adiponectin level was temporarily reduced from 7.3 +/- 0.9 to 6.2 +/- 0.8
      microg/mL 14 days after the hospitalization (P < 0.01), followed by recovery to
      the basal value. The present findings indicate that serum adiponectin levels are
      equivalently reduced in patients with atherosclerotic disorders, and that serum
      adiponectin is changeable under acute phase of cerebral infarction.

PMID- 17496732
TI  - Chromium picolinate and biotin combination reduces atherogenic index of plasma in
      patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded,
      randomized clinical trial.
AB  - BACKGROUND: The atherogenic index of plasma (AIP), defined as logarithm [log] of
      the ratio of plasma concentration of triglycerides to high-density lipoprotein
      (HDL) cholesterol, has recently been proposed as a predictive marker for plasma
      atherogenicity and is positively correlated with cardiovascular disease risk. The
      nutrient combination of chromium picolinate and biotin (CPB) has been previously
      shown to reduce insulin resistance and hyperglycemia in patients with type 2
      diabetes (T2DM). METHODS: Thirty-six moderately obese subjects with T2DM and with
      impaired glycemic control were randomized to receive CPB or placebo in addition
      to their oral hyperglycemic agents for 4 weeks. Measurements of blood lipids
      (including ratio of triglycerides to HDL cholesterol), fructosamine, glucose, and
      insulin were taken at baseline and after 4 weeks. RESULTS: At the final visit,
      the active group had a significantly lower AIP compared to the placebo group (P <
      0.05). A significant difference in triglyceride level (P < 0.02) and the ratio of
      low-density lipoprotein (LDL) to HDL cholesterol (P < 0.05) was also observed
      between the groups at the final visit. In the active group, the changes in
      urinary chromium levels were inversely correlated with the change in AIP (P <
      0.05). Urinary chromium levels were significantly increased in the CPB group. In
      the CPB group, glucose levels decreased at 1 hour and 2 hours and glucose area
      under the curve and fructosamine level were significantly decreased. Ratios of
      total to HDL cholesterol, LDL to HDL cholesterol, and non-HDL to HDL cholesterol
      were significantly decreased between the treatments at final visit. No
      significant adverse events were observed in the CPB or placebo groups.
      CONCLUSIONS: These results suggest that the combination of chromium picolinate
      and biotin may be a valuable nutritional adjuvant therapy to reduce AIP and
      correlated CVD risk factors in people with T2DM.

PMID- 17496733
TI  - Decreased hemoglobin levels are associated with higher plasma level of
      fibrinogen, irrespective of age.
AB  - BACKGROUND: Increased plasma levels of fibrinogen are been associated with an
      increased risk of cardiovascular accident. We aimed at verifying whether the
      changes of fibrinogen levels are associated with red blood cell (and/or
      hemoglobin) concentration. METHODS: A group of 381 carefully selected healthy
      volunteers (219 male and 162 female), aged from 18 to 101 years, were enrolled in
      this study. Fasting blood samples were taken and all measurements (fibrinogen
      plasma level, whole blood viscosity, hemoglobin concentration, hematocrit value,
      red blood cell and white blood cell count, platelet count, glucose, total
      cholesterol and triglycerides plasma concentration, and C-reactive protein level)
      were obtained with standardized methodology using appropriate equipment,
      procedures, and controls. RESULTS AND CONCLUSIONS: In the male but not in the
      female group, plasma fibrinogen concentration inversely correlated with
      hemoglobin (P < 0.0001) and hematocrit value (P < 0.01). In a post hoc analysis,
      plasma fibrinogen level inversely correlated with hemoglobin in the subgroup of
      the 93 premenopausal women and directly correlated with age and inversely
      correlated with platelet count in the subgroup of the 69 postmenopausal women.
      Results of multiple regression analysis revealed that in all the subjects, except
      in the postmenopausal women, hemoglobin level is an independent predictor of
      fibrinogen plasma level. Considering the physiopathologic role of increased
      plasma fibrinogen concentration and the scarcity of pharmacologic approaches to
      decrease its level, these findings could be important in designing a preventive
      therapy of cardiovascular disease.

PMID- 17496734
TI  - Penicillin resistance not a factor in outcome from invasive Streptococcus
      pneumoniae community-acquired pneumonia in adults when appropriate empiric
      therapy is started.
AB  - BACKGROUND: Invasive Streptococcus pneumoniae pneumonia among adults due to
      penicillin-resistant or intermediate resistant strains was investigated to
      determine whether these patients responded poorly to common antibiotic regimens
      compared to pneumonia due to susceptible strains. METHODS: During a 21-year
      period (1983-2003), clinical outcome was analyzed among 3 groups of adults, 19
      with resistant, 33 with intermediate, and 133 with susceptible invasive S
      pneumoniae pneumonia admitted to hospitals in Huntington, West Virginia. Adults
      with resistant and intermediate infections were matched by age and month of
      admission to a group of 133 adults with penicillin-susceptible infections. All
      isolates of resistant and intermediate infections were capsular
      serotypes/serogroups 6, 9, 14, 19, and 23, and isolates of susceptible infections
      included 24 different serotypes/serogroups. Case fatality rates were calculated
      for deaths that occurred during the first 7, first 14, and first 21 days of
      hospitalization. Minimal inhibitory concentration (MIC) was determined by E-test
      and capsular serotype by Quellung procedures. RESULTS: The resistant and
      susceptible groups did not differ in several measures of severity of illness,
      including admission vital signs, duration of fever, mean total leukocyte count,
      number of lobes involved, preexisting underlying diseases, and antibiotic
      treatment regimens. There were no significant differences in case fatality rates
      between the 3 groups of pneumonia by days in hospital, age, severity of illness,
      and empiric antibiotic treatment regimen with a cephalosporin and a macrolide,
      the most common antibiotic regimen. CONCLUSIONS: These findings provide evidence
      that combination antibiotic regimens effective in the treatment of invasive
      susceptible S pneumoniae pneumonia are equally effective in the treatment of
      invasive resistant (MIC = 2-4 microg/mL) and of intermediate (MIC = 0.1-1
      microg/mL) S pneumoniae pneumonia.

PMID- 17496735
TI  - Effect of combination lipid-modifying therapy on the triglyceride lowering effect
      of fish oil.
AB  - BACKGROUND: Marine fish oil supplements are frequently administered with other
      lipid medications for treatment of hypertriglyceridemia. The efficacy of fish oil
      may be reduced in the presence of other lipid agents, particularly fibrates that
      also act as PPARalpha agonists. We therefore sought to determine the efficacy of
      fish-oil supplements when coadministered with other lipid-modifying agents.
      METHODS: Patients receiving fish oil supplements were identified from the
      computer database of a large governmental HMO. Change in plasma lipoprotein
      levels after administration of fish oil was compared between patients receiving
      fish oil as their only treatment and those for whom fish oil was added to other
      drugs. RESULTS: A total of 166 evaluable records were identified, 66 from
      patients treated with fish oil alone and 100 from patients for whom fish oil was
      added to another agent or other agents. Fish oil effectively reduced triglyceride
      levels to an equal extent in the fish oil only and fish oil added groups (-30%
      versus -27% respectively; P = 0.84). CONCLUSION: Fish oil effectively reduces
      plasma triglyceride levels when administered with concomitant lipid medications.
      These findings suggest the presence of additional and even complementary
      mechanisms of action of fish oil to lower triglyceride when added to other lipid
      drugs. These findings validate the common clinical practice of combining fish oil
      supplements with other lipid-lowering medications in patients with
      hypertriglyceridemia.

PMID- 17496736
TI  - Cushing syndrome caused by topical corticosteroid: a case report.
AB  - Development of iatrogenic Cushing syndrome from topical steroid therapy is very
      rare in adults. A 48-year-old woman with a diagnosis of Cushing syndrome caused
      by long-term topical clobetasol propionate application was presented. Laboratory
      studies were consistent with adrenal suppression that improved after
      discontinuation of the use of topical glucocorticoids. Patients who will take
      treatment with steroids, even with topical steroids, should be offered
      information about the dose, duration, and type of the treatment and its systemic
      side-effects.

PMID- 17496737
TI  - Chorea-ballism as a manifestation of decompensated type 2 diabetes mellitus.
AB  - Chorea and ballism are movement disorders that result from a variety of
      conditions. Hyperglycemia is an unusual recognized cause of these movement
      disorders. We report 3 cases of new-onset chorea-ballism induced by nonketotic
      hyperglycemia in elderly patients, highlighting that chorea may be the first
      manifestation of undiagnosed decompensated diabetes mellitus.

PMID- 17496738
TI  - Primary hyperaldosteronism associated with vitiligo vulgaris and autoimmune
      hypothyroidism.
AB  - Type 3 polyendocrine autoimmune syndrome (PAS) is defined as the association
      between an autoimmune thyroid disease and 1 or more other autoimmune diseases,
      except for autoimmune Addison disease or hypoparathyroidism. Here we report an
      extremely rare case of type 3 PAS in which vitiligo vulgaris and symptomless
      autoimmune hypothyroidism were observed during the study of primary
      hyperaldosteronism.

PMID- 17496739
TI  - Piperacillin/tazobactam-induced seizure rapidly reversed by high flux
      hemodialysis in a patient on peritoneal dialysis.
AB  - Despite popular use of piperacillin, the dire neurotoxicity associated with
      piperacillin still goes unrecognized, leading to a delay in appropriate
      management. We report a 57-year-old woman with end-stage renal disease receiving
      continuous ambulatory peritoneal dialysis (CAPD), who developed slurred speech,
      tremor, bizarre behavior, progressive mental confusion, and 2 episodes of
      generalized tonic-clonic seizure (GTCS) after 5 doses of piperacillin/tazobactam
      (2 g/250 mg) were given for bronchiectasis with secondary infection. The
      laboratory data revealed normal plasma electrolyte and ammonia levels but
      leukocytosis. Neurologic examinations showed dysarthria and bilateral Babinski
      sign. Computed tomography of brain and electroencephalogram were unremarkable.
      Despite the use of antiepileptic agents, another GTCS episode recurred after the
      sixth dose of piperacillin/tazobactam. Brain magnetic resonance imaging did not
      demonstrate acute infarction and organic brain lesions. Initiation of high-flux
      hemodialysis rapidly reversed the neurologic symptoms within 4 hours.
      Piperacillin-induced encephalopathy should be considered in any uremic patients
      with unexplained neurological manifestations. CAPD is inefficient in removing
      piperacillin, whereas hemodialysis can rapidly terminate the piperacillin-induced
      encephalopathy.

PMID- 17496740
TI  - A case of hypomyopathic dermatomyositis associated with rapid progressive
      interstitial pneumonia resistant to multi-immunosuppressive therapy.
AB  - The prognosis of interstitial pneumonia in patients with dermatomyositis is
      thought to depend on the histologic type and response to therapy. We report a
      case of hypomyopathic dermatomyositis with rapid development of a fatal
      interstitial pneumonia. Although the histology of lung biopsy indicated minimal
      alveolitis, the patient died despite multi-immunosuppressive therapy. The autopsy
      revealed acute and organizing diffuse alveolar damage. In this case, the lung
      biopsy taken before the acute deterioration did not predict the patient's poor
      prognosis. Interstitial pneumonia in patients with amyopathic or hypomyopathic
      dermatomyositis would develop rapidly progressive and refractory. We need larger
      and better prospective studies to determine whether early and intensive
      immunosuppressive therapy improves the prognosis of interstitial pneumonia in
      patients with amyopathic or hypomyopathic dermatomyositis.

PMID- 17496741
TI  - Combined herpes viral and candidal esophagitis in a CAPD patient: case report and
      review of literature.
AB  - Concomitant herpetic and candidal esophagitis is a very rare disease that had not
      been reported in uremic patients. A 57-year-old woman receiving continuous
      ambulatory peritoneal dialysis (CAPD) therapy for 3 years was admitted due to
      CAPD-related peritonitis. Endoscopic examination was performed due to severe
      epigastralgia and upper gastrointestinal bleeding, and combined herpetic and
      candidal esophagitis was diagnosed. Intravenous acyclovir and fluconazole were
      prescribed and symptoms improved. The patient subsequently died due to
      progressive sepsis and respiratory failure. This is the first report of a dual
      infectious esophagitis in a uremic patient. Since infectious esophagitis may
      cause severe complications, early diagnosis and aggressive treatment are
      important.

PMID- 17496742
TI  - Clomiphene-induced acute pancreatitis without hypertriglyceridemia.
AB  - Acute pancreatitis may be caused by drugs. In the literature, there are more than
      260 different drugs that have been blamed for causing pancreatitis. Among these
      drugs, only 1 case has been reported as clomiphene-induced acute pancreatitis.
      However, in this single case, there was concomitant hypertriglyceridemia. We
      report the case of a woman who developed 2 attacks of acute pancreatitis without
      hypertriglyceridemia while receiving treatment with clomiphene.

PMID- 17496743
TI  - Prosthetic valve endocarditis due to Acinetobacter spp: a rare case and
      literature review.
AB  - A rare case of prosthetic valve endocarditis from Acinetobacter spp occurring 9
      months postoperatively is described. The patient initially received empirical
      therapy against pathogens commonly associated with prosthetic valve endocarditis,
      but his condition did not improve. Identification of bacteremia due to
      Acinetobacter spp was not attributed to any of the classic nosocomial factors
      such as presence of a catheter or a recent invasive procedure. The patient did
      well with an intravenous regimen of meropenem and tobramycin instituted according
      to susceptibility testing. Physicians should be aware of this rare association of
      a nosocomial pathogen such as Acinetobacter spp with prosthetic valve
      endocarditis occurring long after the initial cardiothoracic procedure.

PMID- 17496744
TI  - Joint contractures.

PMID- 17496745
TI  - The correction of deformity at the hip, the result of disease: a study of the
      best methods and best positions. 1903.

PMID- 17496746
TI  - Joint contractures: comment on the classics.

PMID- 17496747
TI  - On the treatment of ankylosis by the formation of artificial joints. 1827.

PMID- 17496748
TI  - Deformities of the human frame. 1843.

PMID- 17496749
TI  - Ischaemic muscle paralyses and contractures. 1881.

PMID- 17496750
TI  - Statins and dietary fish oils improve lipid composition in bone marrow and
      joints.
AB  - There have been numerous efforts to alter the lipid content of cardiovascular
      tissues. Although equally important, only limited information is available about
      musculoskeletal tissues. I characterized joint and bone marrow lipids in patients
      having joint replacement surgery and explored the effects of fish oils and
      statins on lipid composition in bone marrow and joint fluid. Joint drainage
      catheters were used to collect marrow lipids from 84 patients having 128 hip and
      knee replacements for osteoarthritis, osteonecrosis, and femoral neck fractures
      (osteoporosis). Statins reduced the amount of lipid by 22% in patients with
      osteoporosis, 26% in patients with osteoarthritis, and 41% in patients with
      osteonecrosis compared with pretreatment lipid levels in the same patients.
      Taking fish oils reduced the amount of lipid in bone marrow by 20%. Lipid
      profiles of disturbed marrow and joint fluid from patients who took statins or
      dietary fish oil showed an increase in the proportion of unsaturated fatty acids
      and longer-chain fatty acids relative to pretreatment profiles. The ability to
      change the amount and character of bone and joint lipids may have major
      importance for strengthening bone, reducing the severity or preventing
      osteonecrosis, and enhancing joint lubrication.

PMID- 17496751
TI  - The use of corticosteroids in the treatment of painful and still shoulders.

PMID- 17496754
TI  - Use of inhaled nitric oxide in the preterm infant.
AB  - PURPOSE OF REVIEW: Inhaled nitric oxide is established therapy for term infants
      with hypoxemic respiratory failure. Laboratory studies demonstrate that inhaled
      nitric oxide improves lung function and morphology in animal models of
      bronchopulmonary dysplasia, creating a rationale for clinical studies in
      premature infants. Four large multicenter randomized trials have now completed
      enrollment, and one trial has reported neurodevelopmental outcomes at 18-22
      months. The purpose of this review is to summarize the results of the most recent
      preclinical studies and clinical trials. RECENT FINDINGS: In 2006, short-term
      outcomes from two large multicenter randomized trials were published. These
      studies differed in their target population and study design. Early use of
      inhaled nitric oxide was associated with a decrease in brain injury, and
      decreased chronic lung disease in infants over 1000 g. Inhaled nitric oxide use
      in older infants (7-21 days) was associated with decreased chronic lung disease,
      particularly if started early. SUMMARY: Neurodevelopmental outcomes after
      discharge are still needed from three large multicenter randomized trials. These
      results will help confirm the long-term implications of the benefits reported in
      the two most recent trials.

PMID- 17496755
TI  - Safety and effectiveness of permissive hypercapnia in the preterm infant.
AB  - PURPOSE OF REVIEW: Bronchopulmonary dysplasia continues to be an important cause
      of morbidity in premature infants who require mechanical ventilation. Management
      strategies have historically focused on normalizing blood gases but new research
      suggests that a higher PCO2 level may be well tolerated in premature infants.
      There are physiologic rationale and recent experimental data to support the
      potential benefits of permissive hypercapnia. RECENT FINDINGS: Higher PCO2 levels
      may allow a reduction in ventilatory support which reduces the risk of lung
      injury in intubated patients. Targeting PCO2 levels above 45 mmHg has been tested
      in randomized controlled trials. These trials report that neonates managed with
      permissive hypercapnia have a shorter duration of mechanical ventilation and
      reduced severity of bronchopulmonary dysplasia without an increase in adverse
      events. SUMMARY: Permissive hypercapnia appears as a safe and effective
      management strategy to decrease morbidity from bronchopulmonary dysplasia in
      premature infants. Although the preliminary results are promising, further
      research is needed to determine whether this strategy improves pulmonary outcomes
      without adverse effects.

PMID- 17496756
TI  - Identifying infants at risk for sudden infant death syndrome.
AB  - PURPOSE OF REVIEW: This review examines recent research relevant to the
      underlying pathophysiology and risk factors for sudden infant death syndrome.
      RECENT FINDINGS: Current research focuses on the linkage between known risk
      factors and vulnerability, genetic contributions, and the role of dysfunctional
      brainstem neurotransmission in the pathogenesis of this syndrome. While social
      inequalities, prematurity, maternal smoking, infant sleeping practices and sleep
      environment, arousal failures and environmental pollutants remain important risk
      factors, new evidence is emerging that certain genetic polymorphisms may
      contribute to vulnerability. New neuropathological studies have provided strong
      support for abnormal brainstem serotonergic function. Since serotonin influences
      a wide range of physiological systems including breathing, the cardiovascular
      system, temperature, and sleep-wake cycles, this finding strongly supports the
      hypothesis that sudden infant death syndrome is the result of dysregulation of
      the autonomic nervous system and provides biological plausibility for certain
      risk reduction strategies. SUMMARY: Despite a putative diagnostic shift, sudden
      infant death syndrome remains the most common cause of death from 1 month to 1
      year of age. Recent studies confirmed established risk factors and have suggested
      new genetic vulnerabilities. Finally, new evidence supports a key role for
      abnormalities in brainstem serotonin systems in the pathophysiology of this
      syndrome.

PMID- 17496757
TI  - Surfactant for respiratory distress syndrome: are there important clinical
      differences among preparations?
AB  - PURPOSE OF REVIEW: Respiratory distress syndrome is the leading cause of
      mortality and morbidity among infants born prematurely. The disorder arises from
      the developmental and biochemical abnormalities associated with preterm delivery.
      The decreased number of type II alveolar pneumocytes results in absent or reduced
      surfactant production, which leads to alveolar instability and a tendency to
      collapse during expiration and increased work of breathing necessitating the
      institution of supplemental oxygen therapy and positive pressure mechanical
      ventilation. RECENT FINDINGS: Exogenous surfactant replacement therapy has been
      shown to be effective in the treatment of neonatal respiratory distress syndrome
      and has become a standard of care in neonatal intensive care units. A number of
      controversies still exist over a number of issues, however, such as the
      comparative effectiveness of one surfactant preparation over another, timing of
      administration, dosing volumes and short versus long-term benefits. Furthermore,
      the emergence of a newer generation of synthetic, peptide-containing surfactants
      has opened a new era in surfactant therapy which may have implications for future
      practice and research. SUMMARY: This paper discusses these developments and
      analyses the effectiveness of surfactant therapy against respiratory distress
      syndrome by appraising the evidence produced from published trials and systemic
      reviews.

PMID- 17496758
TI  - Aerosolized surfactants.
AB  - PURPOSE OF REVIEW: To present existing data on the potential use of aerosolized
      surfactants for treatment of neonatal respiratory distress syndrome in the era of
      noninvasive ventilatory support. RECENT FINDINGS: Current surfactant therapy
      requires endotracheal intubation and application of positive pressure
      ventilation. Instillation of the drug itself can be complicated by 'peridosing
      adverse events' including, but not limited to, desaturations, bradycardias,
      changes in blood pressure, drug reflux and even the need for reintubations.
      Increasing use of noninvasive ventilatory support for neonatal respiratory
      distress syndrome has motivated clinicians and researchers to look for alternate
      ways of introducing surfactants to patients. Aerosolized surfactants have been
      tested in animal models of respiratory distress syndrome. In addition, four small
      clinical studies have been performed to date. The effectiveness of this form of
      treatment requires further study, however, which will need to include optimizing
      the dose of aerosolized surfactant, choosing particle size, developing the best
      delivery system, and using a surfactant formulation that maintains its activity
      once aerosolized. SUMMARY: Aerosolized surfactants for neonatal respiratory
      distress syndrome may prevent the need for endotracheal intubation. Appropriately
      designed randomized controlled studies are required to determine if this form of
      surfactant administration is as effective and safe as tracheal instillation.

PMID- 17496760
TI  - Evaluation of hypertension by the general pediatrician.
AB  - PURPOSE OF REVIEW: To summarize the recommended work-up in a child who presents
      with elevated blood pressure as well as innovative evaluation techniques under
      development. RECENT FINDINGS: 'The fourth report on the diagnosis, evaluation,
      and treatment of high blood pressure in children and adolescents' contains
      several updates on the diagnosis, evaluation and treatment of childhood
      hypertension. New risk factors for hypertension have been identified and include
      obesity, sleep apnea, and low birth weight. The roles of uric acid, leptin and C
      reactive protein in the pathophysiology of hypertension have been examined. The
      presence of hypertensive end-organ damage has been demonstrated in hypertensive
      children. SUMMARY: Current knowledge emphasizes the need to diagnose and treat
      hypertension when it develops in childhood to decrease the risk of cardiovascular
      morbidity in adulthood. End-organ injury is evident, illustrated by the presence
      of left ventricular hypertrophy, even in young children. Assessment for the
      presence of comorbidities and end-organ damage should be emphasized. Further
      study is needed to isolate the etiologic factors for childhood hypertension,
      improve evaluation techniques, and determine if end-organ damage is reversible
      with proper therapy.

PMID- 17496761
TI  - Hypertension in children: an update on treatment strategies.
AB  - PURPOSE OF REVIEW: Hypertension is among the more prevalent treatable diseases
      that afflict children. Pediatric hypertension carries significant short-term
      morbidity and long-term risk for the development of cardiovascular disease. This
      review addresses issues significant to the chronic management of hypertension and
      discusses common pharmacological agents currently used to treat elevated blood
      pressure in children. RECENT FINDINGS: The recent change in the Federal 2002 Best
      Pharmaceuticals for Children Act has led to the study and approval of new
      antihypertensive medications for use in pediatrics. Several antihypertensive
      medications are commercially available in liquid form or can be extemporaneously
      compounded for flexible dosing and ease of administration. SUMMARY: The
      availability of normative blood pressure data and several pharmacologic
      antihypertensive agents makes early detection and treatment of hypertension in
      children a realizable goal. The long-term effect of chronic antihypertensive
      therapy on growth, as well as the prevention of future development of
      cardiovascular disease, is not fully understood.

PMID- 17496762
TI  - Ambulatory blood pressure monitoring: what a pediatrician should know.
AB  - PURPOSE OF REVIEW: Ambulatory blood pressure monitoring is a useful tool for the
      evaluation and management of hypertension in children and adolescents. This
      review provides a basic overview of ambulatory blood pressure monitoring and
      summarizes the most recent available knowledge regarding its use in the pediatric
      population. RECENT FINDINGS: Evaluation and validation of ambulatory blood
      pressure monitoring equipment in children remains limited, although advances in
      the interpretation of results for this age group have been reported specifically
      in the area of circadian (24 h) and ultradian (<24 h) variability. Blood pressure
      is a dynamic phenomenon that varies not only with time but also with changing
      patient and environmental circumstances. Growing evidence regarding conditions
      identified when this variability is considered, specifically white coat and
      masked hypertension, suggests that office blood pressure measurement may not be a
      sufficient screening test for hypertension-related target-organ damage. SUMMARY:
      Information regarding ambulatory blood pressure monitoring use in children is
      increasing, although due to its limitations and expense, it remains a tool
      primarily utilized by the pediatric sub-specialist.

PMID- 17496763
TI  - Update on the metabolic syndrome in children.
AB  - PURPOSE OF REVIEW: Provides an update on the metabolic syndrome in childhood.
      RECENT FINDINGS: The metabolic syndrome is increasingly recognized among
      children. It is nearly exclusively encountered in overweight and obese
      individuals and is associated with atherosclerosis. Development and clustering of
      cardiovascular risk factors is influenced by many characteristics including
      heritable traits, prenatal and infantile influences, diet, physical activity, and
      socioeconomic status. SUMMARY: Epidemiological data have become mature in this
      area. Efforts to design and implement systems to prevent and treat the metabolic
      syndrome are required.

PMID- 17496764
TI  - Advances in genetic hypertension.
AB  - PURPOSE OF REVIEW: Mendelian forms of hypertension are rare genetic disorders
      that cause severe hypertension. This review will explore the recently identified
      molecular mechanisms and pathogenesis of genetic disorders that cause
      hypertension in children. RECENT FINDINGS: Hypertension is now believed to be a
      polygenic disorder resulting from the interaction of multiple genes and the
      environment. A few forms of severe hypertension have been linked to single genes.
      The genes responsible for these disorders have all been cloned and all
      participate in pathways involved in heightened renal sodium reabsorption. The
      increased sodium reabsorption arises in the distal nephron and leads to volume
      expansion and hypertension. SUMMARY: Investigating forms of monogenic
      hypertension has advanced the understanding of sodium transport and volume
      control by the kidney. Future studies will identify novel genes, pathways and
      treatment targets important in the fight against primary hypertension.

PMID- 17496765
TI  - Old antidotes, new antidotes, and a 'universal antidote': what should we be using
      for pediatric poisoning?

PMID- 17496766
TI  - Physostigmine: is there a role for this antidote in pediatric poisonings?
AB  - PURPOSE OF REVIEW: Ingestion of anticholinergic medications is common in
      pediatrics. Toxicity may result in symptoms such as severe agitation requiring
      physical restraint. Physostigmine, an antidote for anticholinergic poisoning,
      could be useful in this situation. Many physicians are hesitant to use
      physostigmine after case series suggested its use in tricyclic antidepressant
      overdose was associated with asystole. This paper reviews the anticholinergic
      toxidrome and pathophysiology, recent literature on the efficacy and toxicity of
      physostigmine, and its dosing, indications, and contraindications. RECENT
      FINDINGS: Recent articles suggest that toxicity associated with physostigmine
      consists mostly of seizures and cardiac arrhythmia, and occurs when used in the
      absence of anticholinergic symptoms. Despite potential complications,
      physostigmine has been shown to be useful in cases of confirmed anticholinergic
      poisoning by controlling agitation and reversing delirium, and appears to be
      safer and more effective than benzodiazepines in this situation. SUMMARY: In the
      proper clinical situation such as pure anticholinergic overdose with severe
      symptoms, physostigmine can be beneficial. The potential for side effects is not
      insignificant, and the antidote should be used with caution in any patient with
      unknown ingestions or those with cardiac conduction defects. More research is
      needed, especially involving children, before we will fully understand the
      indications and toxicities associated with physostigmine.

PMID- 17496767
TI  - Carnitine as an antidote for acute valproate toxicity in children.
AB  - PURPOSE OF REVIEW: Valproic acid is a widely used anticonvulsant that has
      recently been approved for stabilization of manic episodes in patients with
      bipolar disorder. As the use of valproic acid increases, the number of both
      accidental and intentional exposures increases. This is paralleled by more
      reports of valproic-acid-induced toxicity. The purpose of this article is to
      review the pathophysiology and toxicology of valproic acid and determine whether
      the literature supports the use of carnitine as a treatment for acute valproic
      acid-induced toxicity. RECENT FINDINGS: Recent literature documents no cases of
      allergic reactions or serious side effects associated with the administration of
      carnitine when given patients with acute ingestions of valproic acid. Other
      findings suggest that carnitine increases the survival rate of patients who
      develop valproic-acid-induced hepatotoxicity. Early intervention with intravenous
      rather than enteral L-carnitine was associated with the greatest hepatic
      survival. Isolated pediatric case reports show that carnitine administration may
      reverse toxic metabolic pathways but may not hasten clinical improvement.
      SUMMARY: Based on this recent literature, it seems reasonable to use carnitine
      for documented severe valproic acid toxicity, particularly in cases where
      patients present with coma, rising ammonia level, or valproic acid levels greater
      than 450 mg/l.

PMID- 17496768
TI  - Antidotes for nerve agent poisoning: should we differentiate children from
      adults?
AB  - PURPOSE OF REVIEW: Chemical terrorism presents a threat to the civilian
      population, including children. Nerve agent antidotes are available in
      prepackaged autoinjectors that can be delivered rapidly following an exposure.
      The published evidence on the use of nerve agent antidotes consists of case
      reports, extrapolation from pediatric organophosphate poisonings, and expert
      opinion. This review examines the evidence supporting the use of nerve agent
      antidotes in children. RECENT FINDINGS: The use of adult formulated atropine and
      pralidoxime autoinjectors will deliver doses above current recommendations for
      infants and children. Data demonstrate, however, that atropine overdose is
      generally well tolerated in young children. Children symptomatic of nerve agent
      poisoning will likely need both supraphysiologic doses and frequent re-dosing of
      atropine. SUMMARY: Based on limited data, the Mark 1 autoinjector kit (Meridian
      Medical Technologies, Columbia, Maryland, USA) appears to be the most efficacious
      antidote delivery system following a nerve agent attack. Symptomatic children
      under 1 year of age should be given a full atropine dose from the Atropen
      (Meridian Medical Technologies) (0.5 mg) or Mark 1 kits (2 mg), while children
      over 1 year of age should be given a full dose of both atropine and pralidoxime
      from the Mark 1 kit when more accurate weight-based dosing of antidotes is
      impossible.

PMID- 17496769
TI  - Activated charcoal for pediatric poisonings: the universal antidote?
AB  - PURPOSE OF REVIEW: For decades, activated charcoal has been used as a 'universal
      antidote' for the majority of poisons because of its ability to prevent the
      absorption of most toxic agents from the gastrointestinal tract and enhance the
      elimination of some agents already absorbed. This manuscript will review the
      history of activated charcoal, its indications, contraindications, and the
      complications associated with its use as reported in the literature. RECENT
      FINDINGS: Recent randomized prospective studies, although with small numbers,
      have shown no difference in length of hospital stay, morbidity, and mortality
      between groups who received and did not receive activated charcoal. No study has
      had sufficient numbers to satisfactorily address clinical outcome in patients who
      received activated charcoal less than 1 h following ingestion. SUMMARY: If used
      appropriately, activated charcoal has relatively low morbidity. Due to the lack
      of definitive studies showing a benefit in clinical outcome, it should not be
      used routinely in ingestions. AC could be considered for patients with an intact
      airway who present soon after ingestion of a toxic or life-threatening dose of an
      adsorbable toxin. The appropriate use of activated charcoal should be determined
      by the analysis of the relative risks and benefits of its use in each specific
      clinical scenario.

PMID- 17496771
TI  - Current world literature. Neonatology and perinatology.

PMID- 17496770
TI  - Update on child maltreatment.
AB  - PURPOSE OF REVIEW: Recent literature regarding assessment, management and
      prevention of child maltreatment will be considered. Unexplained infant and child
      death will also be reviewed. RECENT FINDINGS: Controversies in the evaluation of
      unexpected infant death and inflicted traumatic brain injury are ongoing.
      Evidence continues to accumulate describing the serious long-term sequelae of
      child maltreatment. Studies have examined the earliest beginnings of these
      adverse outcomes commencing in childhood. Despite sustained efforts to develop a
      variety of training and intervention programs, the deployment of these efforts
      has been hampered by the lack of evidence that they make any difference in
      improving recognition of child abuse or in preventing recurrent maltreatment.
      There is a great need in the child abuse field for more formal, rigorous
      assessment of all manner of intervention programs. SUMMARY: Efforts to improve
      the recognition of and management of child abuse need to be sustained. As our
      understanding of child maltreatment continues to grow, evidence-based
      interventions will likely improve outcomes for abused children and their
      families. General pediatricians are often the first to notice signs and symptoms
      of possible child maltreatment; collaboration with hospital-based Child
      Protection Teams is critical when considering the possibility of abuse or
      neglect.

PMID- 17496772
TI  - Collaborative synergy: practice and academic partnerships in evidence-based
      practice.
AB  - In this department, Dr Newhouse highlights hot topics in nursing outcomes,
      research, and evidence-based practice relevant to the nurse administrator. The
      goal is to discuss the practical implications for nurse leaders in diverse
      healthcare settings. Content includes evidence-based projects and decision
      making, locating measurement tools for quality improvement and safety projects,
      using outcome measures to evaluate quality, practice implications of
      administrative research, and exemplars of projects that demonstrate innovative
      approaches to organizational problems. This column describes potential
      collaborations in evidence-based practice between clinical settings and colleges
      or universities.

PMID- 17496773
TI  - Nurse executive leadership competencies for health facility design.
AB  - Nearly US$200 billion of healthcare construction is expected by the year 2015,
      and nurse leaders must expand their knowledge and capabilities in healthcare
      design. The goal of this bimonthly department is to prepare the nurse leader in
      using the evidence-based design process to ensure that new, expanded, and
      renovated hospitals facilitate optimal patient outcomes, enhance the work
      environment for healthcare providers, and improve organizational performance. In
      this article, the editor discusses the leadership competencies that are necessary
      to ensure nursing input into the design of hospitals and healthcare facilities.

PMID- 17496774
TI  - The graduate nurse rotational internship: a successful recruitment and retention
      strategy in medical-surgical services.

PMID- 17496775
TI  - Small state, big problem: Rhode Island nurse leaders take a second look at the
      state's shortage.

PMID- 17496776
TI  - First-receiver hospital decontamination: an 8-step approach to a progressive and
      practical program.
AB  - The effectiveness of hospital decontamination programs begins with planning,
      preparation, and practice. A well-thought-out hospital decontamination program
      encompasses complexities that are not always apparent. In disaster situations,
      the victim, hospital, patients, and staff are placed at serious risk if
      untrained, unprepared employees perform emergency decontamination procedures at
      the hospital-receiving site. The authors describe 8 steps to developing an
      emergency preparedness program and team with decontamination capabilities to
      facilitate emergency response in the first-receiver hospital.

PMID- 17496777
TI  - Lessons learned when Magnet designation is not received.
AB  - Magnet designation is the highest level of acknowledgement accorded healthcare
      organizations in recognition of professional nursing care. After our nursing
      leadership team attended a Magnet conference in 1998, we were inspired, and so
      was our staff. In 2004, we submitted our documentation and were notified that it
      met the criteria, and our site visit was scheduled. We did not receive Magnet
      designation, but we viewed our experience as an opportunity to learn. The authors
      describe how a disappointing outcome was turned into an experience of great
      learning and transformation.

PMID- 17496778
TI  - Nursing research internship: enhancing evidence-based practice among staff
      nurses.
AB  - Many barriers inhibit nurses from using evidence to guide their practice. The
      authors describe the development of a Nursing Research Internship Program
      designed to overcome barriers to evidence-based practice and provide staff nurses
      with an opportunity for professional growth. Evaluation of the program indicates
      it has increased staff nurses' use of the literature to identify and solve
      clinical problems, fostered positive attitudes about research, and led to
      increased professional development activities.

PMID- 17496779
TI  - The magnetism of theory: resonance to radiance.
AB  - Theory was largely considered to be the province of academia until the Magnet
      Recognition Program brought it into the mainstream of hospital nursing practice.
      The author describes how 1 hospital selected a nursing theory and philosophy,
      integrated the concepts across nursing services, and positively affected the
      hospital as a whole. Jean Watson's theory of human caring was chosen because it
      closely aligned with the culture of the organization. Specific implementation
      strategies are discussed, and outcomes of the process are described. This article
      will assist others engaged in similar endeavors.

PMID- 17496780
TI  - Fourteen unit attributes to guide staffing.
AB  - Given the evolving body of academic literature tying patient outcomes to specific
      nurse staffing variables (ratios, education, experience, etc), hospitals are
      increasingly challenged to balance ideal investments in care quality with current
      nurse labor constraints. The Nursing Executive Center conducted structured
      interviews with chief nurses from a cross section of the nation's leading
      hospitals to understand how nursing leaders are incorporating recent academic
      findings in workforce planning and unit-level staffing. Study findings
      demonstrate a clear consensus among chief nurses on which staffing enhancements
      hold the greatest promise for positively impacting each of 14 distinct unit
      attributes.

PMID- 17496781
TI  - Role of acidic cell organelles in the higher nonmelanoma retention of melanoma
      markers based on N-(2-dialkylaminoethyl)benzamides and the cytotoxicity of
      alkylating benzamides.
AB  - Melanoma markers based on both N-(2-dialkylaminoethyl)benzamides and
      lysosomotropic agents comprise a N-(2-dialkylaminoethyl)aminocarbamoyl
      pharmacophore, suggesting that benzamides and lysosomotropic probes should show
      affinity to melanoma and acidic cell organelles. We prepared novel fluorescent N
      (2-dialkylaminoethyl)benzamides to prove this presumption. Lysosomotropic probes
      showed a melanin affinity comparable to benzamides. Lysosomal markers and
      benzamides colocalized in acidic organelles. Various nonmelanoma cell lines
      showed equal benzamide uptake and retention compared with melanoma cells. In
      nonmelanoma cells the amount of retained benzamides correlates with the number of
      acidic cell organelles. Benzamides almost completely failed to accumulate in
      melanoma cells with neutralized acidic organelles but normal melanin content. In
      melanoma retention of benzamides, acidic cell organelles are the main
      determinant. N-(2-dialkylaminoethyl)benzamides are lysosomotropic probes with
      high accumulation in nonmelanoma tumors with many acidic cell organelles.
      Alkylating benzamides were reported previously to show a melanoma unselective, in
      general enhanced cytotoxicity. Alkylating benzamides can act as lysosomotropic
      detergents or as DNA alkylators. The ability of alkylating benzamides to disrupt
      the membrane of lysosomes and cause liberation of lysosomal-trapped fluorescent
      dyes was demonstrated by fluorescence microscopy. Whether they act as an
      alkylating agent or a lysosomotropic detergent in a specific cell line is
      dependent on the amount of acidic cell organelles. In cell lines with small
      amounts of acidic cell organelles alkylating benzamides act as alkylating agents,
      whereas in cell lines with many acidic cell organelles they act as lysosomotropic
      detergents. In cell lines with high amounts of acidic cell organelles they do not
      reach the nucleus.

PMID- 17496782
TI  - Prognostic relevance of baseline and sequential peripheral blood tyrosinase
      expression in 200 consecutive advanced metastatic melanoma patients.
AB  - The relationship between the disease course and the prognostic relevance of
      sequential tyrosinase reverse transcription-PCR assay in the peripheral blood of
      advanced metastatic melanoma patients was ascertained. The clinical usefulness of
      tyrosinase in stage IV melanoma patients is still debated, owing to the wide
      range of variability (positive expression from 30 up to 100% of patients) and the
      possibility of a transient shedding of melanoma cells into the bloodstream. A
      total of 200 consecutive stage IV metastatic patients treated at our department
      were included, 149 with active metastatic disease undergoing systemic therapies
      (group A), and 51 disease free after surgery (group B). For each patient, a
      baseline sample was obtained within 3 weeks of either the clinical/radiological
      demonstration of metastatic disease or the surgical treatment; thereafter,
      tyrosinase determinations were performed at day 1 of each therapy course before
      chemotherapy administration or at each follow-up visit. Tyrosinase expression was
      determined using standard reverse transcription-PCR nested techniques. A baseline
      positive determination was obtained in 72.5% of the patients with active
      metastatic disease (group A) but not in any of the patients who were disease free
      after surgery (group B). Therapy administration induced an early clearance of
      circulating melanoma cells, from 72.5 to 44.9% at the second down to 29.5% at the
      third determination. Tyrosinase expression before the third cycle was
      significantly associated with the clinical response: 56/81 (69.1%) patients with
      a negative tyrosinase determination obtained a response or a stable disease,
      whereas 29/34 (85.3%) patients with a positive test developed a progressive
      disease (P<0.001). A clinical response was observed in all the patients who had a
      negative tyrosinase at the first three determinations, although all patients
      whose first three determinations were positive developed a progressive disease.
      Multivariate analysis showed that baseline tyrosinase status carries an
      independent prognostic value on both overall survival and time to progression;
      moreover, tyrosinase results during follow-up were entered as time-dependent
      covariates in a multivariate analysis and were shown to be the most significant
      prognostic parameter associated to both overall survival and time to progression.
      In particular, the presence of a constant positive expression during follow-up
      was associated with the development of new metastatic sites in 95.6% of patients
      with active metastatic disease. Our results demonstrate that the discrepancies in
      the positive tyrosinase rates reported in the literature are related to the
      disease status at the time of sampling and to chemotherapy administration.
      Tyrosinase expression in the peripheral blood both at baseline and during follow
      up can be considered a reliable prognostic parameter associated with the response
      to treatment, development of new metastatic sites, time to progression and
      survival.

PMID- 17496783
TI  - Prognostic role of circulating melanoma cells detected by reverse transcriptase
      polymerase chain reaction for tyrosinase mRNA in patients with melanoma.
AB  - A need for factors predictive of prognosis is present in patients who are
      diagnosed with malignant melanoma. The detection of circulating melanoma cells by
      reverse transcriptase-polymerase chain reaction for tyrosinase mRNA is a possible
      negative prognostic factor. The aim of this study was to assess the prognostic
      value of reverse transcriptase-PCR for tyrosinase mRNA in peripheral blood
      samples. From January 2000 to February 2003, duplicate blood samples were drawn
      from 114 melanoma patients following surgery and informed consent, and were
      tested with reverse transcriptase-PCR, for tyrosinase mRNA. Outer primers for the
      first PCR were R1 (sense): TTGGCAGATTGTCTGTAGCC and R2 (antisense):
      AGGCATTGTGCATGCTGCT. For the second round of PCR, nested primers were R3 (sense):
      GTCTTTATGCAATGGAACGC and R4 (antisense): GCTATCCCAGTAAGTGGACT. Threshold for
      detection of the technique was determined by adding serially diluted MelJuSo
      cells to healthy volunteer blood samples. Overall, 91 (79.1%) patients tested
      negative for tyrosinase mRNA and 24 (20.9%) tested positive. The number of
      patients who tested positive by stage was 3/38 (7.9%) for stage I, 3/22 (13.6%)
      for stage II, 5/30 (16.7%) for stage III and 13/24 (54.2%) for stage IV (P<
      0.0001). 11/90 (12.2%) patients with no evidence of disease (stage I, II and III)
      tested positive and 13/24 (54.2%) patients with clinically confirmed distant
      metastases (stage IV) tested positive (P<0.00001). With median follow-up of 372
      days or to death (range: 0-1303 days), median progression-free survival has not
      been reached for tyrosinase-negative patients and was 265 days for tyrosinase
      positive patients (P<0.00001, log-rank test=21.07). Median overall survival was
      344 days for tyrosinase-positive patients and has not been reached for tyrosinase
      negative patients (P=0.0001, log-rank test=21.38). Stage, Breslow thickness and
      result of RT-PCR were significant prognostic factors for disease-free survival in
      a multivariate analysis, and stage was the only significant prognostic factor for
      overall survival. In conclusion, detection of circulating melanoma cells by
      reverse transcriptase-PCR for tyrosinase mRNA is a significant adverse prognostic
      factor for disease-free survival in patients with malignant melanoma.

PMID- 17496785
TI  - The Y152X MC1R gene mutation: occurrence in ethnically diverse Jewish malignant
      melanoma patients.
AB  - MC1R sequence variants are associated with malignant melanoma risk, and most
      commonly are missense mutations. Few (n=9) truncating mutations have been
      described in this gene as predisposing to malignant melanoma. In this study,
      three Jewish individuals were found to harbor an identical truncating MC1R
      mutation--Y152X: an Ashkenazi patient with two malignant melanomas, a non
      Ashkenazi malignant melanoma patient with familial malignant melanoma and her
      asymptomatic mother. Both malignant melanoma patients carried additional,
      seemingly pathogenic MC1R variants. Haplotype analysis revealed that all three
      mutation carriers shared the same haplotype. This sequence variant was previously
      described in ethnically diverse, non-Jewish individuals and in all likelihood
      represents an error-prone domain that, in conjunction with other genetic and
      environmental factors, increases malignant melanoma risk.

PMID- 17496786
TI  - Molecular genetic analysis of NBS1 in German melanoma patients.
AB  - The aim of this study was to investigate the role of NBS1 in the pathogenesis of
      malignant melanoma of the skin. To exclude the common 657del5 founder mutation, a
      total of 376 melanoma patients from Southern Germany were analyzed for sequence
      alterations in exon 6 of NBS1 by direct sequencing. Analyses revealed one 657del5
      mutation and three nonsynonymous sequence variations in exon 6 of NBS1 (V210F,
      R215W, and F222L). Analysis of an additional sample of 629 melanoma patients and
      604 controls revealed no F222L mutation, indicating that this newly identified
      sequence alteration is not a common polymorphism. In a case-control association
      study including 632 melanoma patients and 615 cancer-free control participants
      from Southern Germany, three publicly known single nucleotide polymorphisms
      located in the NBS1 gene region were analyzed. No significant associations
      between single nucleotide polymorphisms (rs9995, rs867185 and rs1063045) or
      referring calculated haplotypes and melanoma risk were identified. These results
      suggest that NBS1 does not play a major role in predisposition to melanoma in the
      Southern German population but that alterations of this gene might contribute to
      the risk of this cancer.

PMID- 17496784
TI  - CCAAT displacement protein regulates nuclear factor-kappa beta-mediated chemokine
      transcription in melanoma cells.
AB  - Members of the nuclear factor-kappa beta (NF-kappaB) family maintain cellular
      homeostasis by enhancing the transcription of genes involved in inflammation,
      immune response, cell proliferation, and apoptosis. Melanoma tumor cells often
      express inflammatory mediators through enhanced activation of NF-kappaB. The NF
      kappaB activation appears to result from the enhancer formation including NF
      kappaB and lysine acetyl transferases such as p300, CREB (cyclic AMP-responsive
      element binding protein)-binding protein (CBP), and/or p300/CBP associating
      factor (PCAF). We observed that proteins expressed by Hs294T metastatic melanoma
      cells are highly acetylated compared with normal melanocytes, and dominant
      negative PCAF reduced the basal and tumor necrosis factor-alpha-stimulated
      transcriptional activity of NF-kappaB. The promoter activity of NF-kappaB
      regulated chemokines was also reduced by the expression of dominant-negative
      PCAF. The promoters of these chemokines contain a CCAAT displacement protein
      (CDP)-binding site near the NF-kappaB element. compared with vector-transduced
      cells, in CDP-transduced Hs294T cells: (i) over-expressed CDP bound efficiently
      to PCAF, (ii) tumor necrosis factor-alpha-stimulated chemokine expression and NF
      kappaB-mediated transcription were reduced, and (iii) the binding of CBP to Rel A
      was reduced. These data suggest that CDP inhibits cytokine-induced NF-kappaB
      regulated chemokine transcription. This study contributes to our understanding of
      the role of CDP in an enhanceosome of NF-kappaB-mediated chemokine transcription
      in human melanoma cells.

PMID- 17496787
TI  - Diagnosis and treatment of cutaneous melanoma: state of the art 2006.
AB  - Although the incidence of melanoma is still rising in Caucasian populations, the
      increase in mortality has leveled off. Improvements in early diagnosis, with more
      frequent diagnosis of low-risk patients (i.e. those with <1 mm of tumor
      thickness), is the main reason for these divergent developments. Primary
      prevention has not yet been successful and recent studies have demonstrated the
      lack of effectiveness of sunscreen in preventing nevi in children. Progress was
      made in early melanoma diagnosis when dermoscopy and digital dermoscopy were
      introduced, and computer algorithms have proved to be highly efficacious for
      automated melanoma diagnosis. Primary melanomas are now excised with narrower
      surgical margins of 1-2 cm. Sentinel-node biopsy is recommended as a nodal
      staging procedure in patients with tumor thickness of 1 mm and more, but the
      prognostic impact of this procedure has not yet been demonstrated. New imaging
      techniques, e.g. whole-body MRI and PET-CT, provide more accurate staging,
      particularly in patients with apparent metastasis, and facilitate decisions on
      surgical treatment strategies. Staging is now based on the 2001 TNM
      classification including tumor thickness and histopathologic ulceration in stages
      I and II and lymph node micro and macro-metastasis in stage III. A stage- and
      risk-adopted follow-up schedule is proposed for melanoma surveillance. Adjuvant
      therapy with interferon-alpha in high-risk patients offers a small benefit in
      terms of recurrence-free and overall survival; the optimal dosage and duration of
      this treatment are still to be defined. Almost no progress has been made in the
      medical treatment of disseminated metastasis of melanoma. Therapy with
      dacarbazine and a few other single agents remains the first-line treatment
      approach of choice. A number of new treatment modalities, including targeted
      molecules and immunologic approaches with monoclonal antibodies, are under
      development; hopefully, new treatment modalities will be available in the near
      future.

PMID- 17496788
TI  - The melanoma epidemic debate: some evidence for a real phenomenon from Tuscany,
      Italy.
AB  - Our objective was to evaluate whether or not recent mortality data for the region
      of Tuscany confirm the hypothesis that an epidemic in the incidence of melanoma
      is an apparent phenomenon reflecting an overdiagnosis of indolent cases. We
      considered 1755 melanoma deaths in Tuscany in the period 1987-2003, and 2644
      incidence cases of melanoma diagnosed in 1985-2003 in a subset of the same
      population. We calculated annual mortality and incidence trends using the
      National Cancer Institute's Joinpoint Program (version 2.6). We observed an
      increasing mortality from melanoma from 1987 to 2003 in both sexes, but mainly in
      women (estimated annual percentage changes=2.25; P<0.05). We also observed a
      statistically significant rise in melanoma incidence in both sexes, mainly of
      thin lesions. Furthermore, we observed an increase in thick lesions, especially
      in females (estimated annual percentage changes=2.9; P<0.05), and for lesions
      without Breslow definition. In conclusion, the rise in melanoma mortality and
      incidence, especially of thick lesions, suggests that the observed growth in
      melanoma incidence is not wholly apparent.

PMID- 17496789
TI  - Reduced pSmad2 immunodetection correlates with increased primary melanoma
      thickness.
AB  - Cutaneous melanoma is the most aggressive of cutaneous neoplasms. Identifying
      patients with an increased risk for the development of metastases is critical.
      This study investigates phospho-Smad2, a central factor of the transforming
      growth factor beta pathway, on formalin-fixed, paraffin-embedded tissues from 60
      primary cutaneous melanomas (Breslow >1 mm), for its candidacy for being a
      prognostic marker in primary cutaneous melanoma. Phospho-Smad2 positivity was
      assessed for correlation with clinical parameters including Breslow index,
      melanoma type, survival, development of metastases, sentinel lymph node status
      and age. Phospho-Smad2 positivity was not associated with survival or development
      of metastases, suggesting that it would not be a useful prognostic marker.
      Despite this, we found phospho-Smad2 positivity to be correlated with low tumour
      thickness, indicating that as the primary tumour grows there is an increased
      inhibition of transforming growth factor beta signalling resulting in suppressed
      Smad2 phosphorylation. Additionally, phosphorylation of Smad2 in neighbouring
      melanoma cells and keratinocytes was interrelated, which is a further indication
      that Smad2 phosphorylation in primary melanoma is affected by local area
      microenvironmental factors. We hypothesize that the observed decrease in
      transforming growth factor beta signalling in thicker primary melanomas is due to
      the increased production of signalling inhibitors.

PMID- 17496790
TI  - In vivo conversion of TIB to MEE not an artifact generated by heat.

PMID- 17496792
TI  - Saccade-related activity in areas 18 and 21a of cats freely viewing complex
      scenes.
AB  - Although saccadic eye movements can radically change the retinal image,
      perceptually their impact is surprisingly small. Here, we investigate possible
      neuronal correlates of saccadic suppression in cats freely viewing natural
      stimuli. By comparing changes attributable to saccadic events with passive
      stimulus changes, we find that during saccades: (i) evoked and induced activity
      is reduced in areas 18 and 21a by equal amounts, (ii) the variability of neuronal
      activity with stimulus category is abolished in both areas, and (iii) the high
      power transient induced by stimulus change is not observed. These results present
      electrophysiological evidence for saccadic suppression at the level of primary
      and higher visual cortex under natural conditions.

PMID- 17496793
TI  - Who is telling what from where? A functional magnetic resonance imaging study.
AB  - The human central-auditory system exhibits distinct lateralization effects
      (speech, space) and encompasses different processing pathways (where, what, who).
      Using spatialized pseudoword utterances, attentional modulation of the networks
      bound to sound source localization ('where'), voice recognition ('who'), and the
      encoding of phonetic-linguistic information ('what') was evaluated by silent
      functional magnetic resonance imaging. The 'where'-pathway was found to be
      restricted to posterior parts of the left superior temporal gyrus, speaker
      ('auditory face') identification exclusively activated temporal lobe structures,
      and the representation of the sound structure of the utterances was associated
      with hemodynamic activation of Broca's area. Speech perception in space,
      therefore, engages at least three distinct neural networks. Furthermore, the
      findings indicate that voice recognition may depend upon template matching within
      auditory association cortex whereas the sequencing of phonetic-linguistic
      information extends to frontal areas.

PMID- 17496794
TI  - Progression of neuronal processing of visual objects.
AB  - We studied, with functional MRI, how neuronal processing for visual objects
      progresses in the human brain by measuring suppressive responses to stimulus
      pairs. Two concentric rectangular frames of slightly different sizes were
      presented such that the smaller frame was shown first, followed by the larger
      dominant frame, with interstimulus intervals of 0, 50 and 240-ms. The functional
      MRI response at 50-ms decreased along the ventral visual pathway. The response at
      240-ms interstimulus interval was suppressed after a fusiform area at which the
      response at 50-ms interstimulus interval was highly suppressed already and the
      responses at 0, 50 and 240-ms interstimulus intervals showed a V-shaped
      dependence on those interstimulus intervals. These observations show a way of
      progression of the information processing along visual object recognition
      pathway.

PMID- 17496795
TI  - Reduced signal of locus ceruleus in depression in quantitative neuromelanin
      magnetic resonance imaging.
AB  - We used a neuromelanin-magnetic resonance imaging technique to investigate
      abnormalities in the locus ceruleus in depression. We examined 20 patients with
      major depression and 43 age-matched controls using a 3 T scanner with a
      neuromelanin-sensitive sequence. The signal intensities of the areas
      corresponding to the rostral, middle, and caudal portions of the locus ceruleus
      were measured, and the contrast ratio relative to the adjacent pontine tegmentum
      was calculated. In controls, the contrast ratio in the middle portion was higher
      than in the rostral and caudal areas. In patients, contrast ratios in the rostral
      and middle portions were significantly decreased in comparison with controls,
      suggesting dysfunction of the ascending noradrenergic system. Neuromelanin
      magnetic resonance imaging can be used to visualize abnormalities in the locus
      ceruleus of depressive patients.

PMID- 17496796
TI  - Theta synchronization networks emerge during human object-place memory encoding.
AB  - Recent rodent hippocampus studies have suggested that theta rhythm-dependent
      neural dynamics ('theta phase precession') is essential for an on-line memory
      formation. A computational study indicated that the phase precession enables a
      human object-place association memory with voluntary eye movements, although it
      is still an open question whether the human brain uses the dynamics. Here we
      elucidated subsequent memory-correlated activities in human scalp
      electroencephalography in an object-place association memory designed according
      the former computational study. Our results successfully demonstrated that
      subsequent memory recall is characterized by an increase in theta power and
      coherence, and further, that multiple theta synchronization networks emerge.
      These findings suggest the human theta dynamics in common with rodents in
      episodic memory formation.

PMID- 17496797
TI  - Anti-myelin basic protein T cells protect hippocampal neurons against
      trimethyltin-induced damage.
AB  - We investigated the influence of administration of autoimmune T cells on
      trimethyltin-induced degeneration of hippocampal neurons. Female Lewis rats
      received 8 mg/kg trimethyltin intraperitoneally alone, or followed 24 h later by
      a second intravenous injection of anti-myelin basic protein T cells (green
      fluorescent protein-tagged). Neurodegeneration was assessed by NeuN and Nissl
      cell counts 21 days after trimethyltin injection. We found that neurodegeneration
      in the CA4 region of the hippocampus was significantly reduced in the group
      receiving T cells. T cells also caused an augmentation of trimethyltin-induced
      hippocampal astrocytic activation and astrocytic TrkA expression, which was
      particularly intense in the CA4 region. Our study provides the first evidence of
      neuroprotection evoked by transferred T cells following a neurotoxic brain
      insult. The data suggest that mediation of the neuroprotective effects of T-cell
      released nerve growth factor occurs mainly via hippocampal astroglial TrkA
      receptors.

PMID- 17496798
TI  - Role of left inferior frontal gyrus in the processing of particles in Japanese.
AB  - Particles are a crucial component of sentences in Japanese. They mainly follow
      nouns, and indicate their thematic role in the sentence, such as agent or
      patient. This study used functional MRI to investigate the neural basis of the
      processing of particles. We compared brain activity when participants were
      required to judge whether a presented character was a particle or whether the
      character as spoken ended with a specific vowel sound. Differential brain
      activity during particle judgment was found only in the left inferior frontal
      gyrus. We further confirmed that this activity was not a feature of categorical
      judgments in general. Our results indicate that the left inferior frontal gyrus
      is involved in the processing of thematic role indicated by Japanese particles.

PMID- 17496799
TI  - Longitudinal changes in neuroanatomy and neural activity in early schizophrenia.
AB  - Although there is substantial evidence indicating that patients with first
      episode schizophrenia exhibit both anatomical and electrophysiological
      abnormalities, there has been little research investigating the relationship
      between these two indices. We acquired structural magnetic resonance images and
      resting electroencephalographic recordings from 19 patients with schizophrenia,
      both at the time of their first presentation to mental health services and 2-3
      years subsequently. Patients' grey matter images were parcellated into four brain
      lobes, and slow-wave, alpha- and beta-electroencephalographic power was
      calculated in four corresponding cortical regions. Although grey matter volume
      decreased longitudinally, particularly fronto-parietally, electroencephalographic
      power increased in the slow-wave and beta-frequency bands. These results suggest
      that first-episode schizophrenia may be associated with abnormally elevated
      levels of neural synchrony.

PMID- 17496800
TI  - Nrsf silencing induces molecular and subcellular changes linked to neuronal
      plasticity.
AB  - Neurite outgrowth involves various molecular mechanisms generating complex brain
      connections. These mechanisms have been linked to plasticity and learning and are
      thought to be deregulated in neuropsychiatric diseases. The transcription factor
      REST/NRSF regulates a subset of genes encoding neurite outgrowth molecules. We
      demonstrate here the downregulation of Rest/Nrsf expression in a mouse
      neuroblastoma cell line. This downregulation induced a clear increase in neurite
      length. Quantitative polymerase chain reaction showed deregulation of the
      candidate genes L1cam, Elmo2, Ulip1 and Ulip2. These genes are bona fide
      candidates known to be involved in dendrite and axonal outgrowth. This approach
      could be adapted to high-throughput techniques for determination of the mammalian
      neurite outgrowth gene repertoire.

PMID- 17496801
TI  - Expression of IP3 receptor isoforms at the nodes of Ranvier in rat sciatic nerve.
AB  - Inositol 1,4,5-trisphosphate receptors (IP3R) are modulated by the second
      messenger IP3, which induces intracellular calcium release. Using
      immunohistochemical techniques, we show that the three isoforms are expressed in
      sciatic nerve. IP3R1 and IP3R2 are mainly present in the nucleus of Schwann
      cells. IP3R1 is also expressed in Schmidt-Lanterman incisures. IP3R3 is primarily
      localized at very high levels in nonmyelinating Schwann cells. Interestingly, the
      three isoforms are expressed at the nodes of Ranvier. IP3R1 is clustered at the
      node of Ranvier, in a distribution that is similar to the Nav1.6 sodium channels
      in the sciatic nerve. IP3R3 is present in the paranodal regions of the nodes.
      IP3R2 is concentrated in the vicinity of the node, and the outer Schwann cell
      cytoplasm similar to the Kv1.5 potassium channel.

PMID- 17496802
TI  - Cortical activation during sequences of memory-guided saccades: a functional MRI
      study.
AB  - Blood oxygenation-level dependent changes in the cerebral cortex were measured
      using event-related functional magnetic resonance imaging in participants while
      they performed triple-step memory-guided saccades. To explore the role of
      dorsolateral prefrontal cortex in the manipulation of the contents of working
      memory, the sequence of saccade targets in the memory-guided task was either
      constant or was manipulated using coloured cues. The dorsolateral prefrontal
      cortex was significantly activated only during the period when participants had
      to reorder the locations of the saccade targets and not during the maintenance of
      spatial locations. This finding suggests that dorsolateral prefrontal cortex is
      primarily involved in the manipulation, and to a lesser extent, in the
      maintenance of the contents of working memory.

PMID- 17496803
TI  - Impaired orientation processing in hemispatial neglect.
AB  - Patients with hemispatial neglect show deficits in size perception. We
      investigated how this effect would be modulated by a change in object
      orientation. Seven right-hemisphere-lesioned patients, with and without neglect,
      and a control group, were asked to indicate which one of two bilaterally
      presented lines was longer, shorter or the same. Depending on the participant's
      response, the length was increased or decreased in a staircase-like procedure.
      Line orientation was varied over separate blocks. All neglect patients judged a
      line on the left as shorter, predominantly for horizontal lines and lines rotated
      by 30 degrees. Moreover, the magnitude of the distortion effect varied
      considerably between patients from as little as 2% objective underestimation to
      as much as 20%.

PMID- 17496804
TI  - Behavioral and neuronal aspects of developmental sensitive periods.
AB  - Neural and behavioral development is characterized by two features. First, brain
      and behavior are organized by an interplay of genetic instruction and information
      from the environment. Second, the acquisition of external information is, in many
      cases, not a steady process. Instead, information is often acquired only for a
      limited time span, the sensitive period. During development, an animal may
      experience many of these sensitive periods, all of them needed for a distinct
      purpose. The basic features of such sensitive periods are described, and the
      neurophysiological basis of the neuronal rewiring that underlies the acquisition
      of early learning is discussed. An example is presented which may serve as a
      general scenario for early learning in sensitive periods.

PMID- 17496805
TI  - Big thoughts in small brains? Dogs as a model for understanding human social
      cognition.
AB  - In this review we argued that dogs can provide a good model for both the
      evolution of human social-cognitive abilities and studying the underlying neural
      and genetic structures of these behavioural features. The key difference between
      the present and other approaches for modelling human social evolution lies in the
      assumption that there is a large overlap between the human and dog behaviour
      complex because during their evolution in close contact with human groups dogs
      evolved functionally similar social skills. Thus the parallel investigation of
      the human and dog behaviour complex widens our possibility for understanding
      human social cognition because it allows the modelling of the interaction between
      various components in contrast to other models which are often restricted to
      modelling a single aspect of human social cognitive skills.

PMID- 17496806
TI  - Limbic and prefrontal responses to facial emotion expressions in
      depersonalization.
AB  - Depersonalization disorder, characterized by emotional detachment, has been
      associated with increased prefrontal cortical and decreased autonomic activity to
      emotional stimuli. Event-related fMRI with simultaneous measurements of skin
      conductance levels occurred in nine depersonalization disorder patients and 12
      normal controls to neutral, mild and intense happy and sad facial expressions.
      Patients, but not controls, showed decreases in subcortical limbic activity to
      increasingly intense happy and sad facial expressions, respectively. For both
      happy and sad expressions, negative correlations between skin conductance
      measures in bilateral dorsal prefrontal cortices occurred only in
      depersonalization disorder patients. Abnormal decreases in limbic activity to
      increasingly intense emotional expressions, and increases in dorsal prefrontal
      cortical activity to emotionally arousing stimuli may underlie the emotional
      detachment of depersonalization disorder.

PMID- 17496807
TI  - Simvastatin treatment prolongs the survival of scrapie-infected mice.
AB  - Statins, drugs that decrease cholesterol biosynthesis, are known to reduce the
      formation of the disease-associated isoform of the prion protein (PrP) in
      neuroblastoma cells in vitro. In this study, we report the effects of
      simvastatin, a clinically approved statin that penetrates the brain, on mice
      infected with the ME7 strain of scrapie. The decline in motor functions
      associated with scrapie infection was delayed in mice receiving (1 mg/kg)
      simvastatin, a dosage used to treat hypercholesterolemia in humans. Simvastatin
      treatment also significantly prolonged the survival times of infected mice (193
      vs. 183 days). These results indicate that low-dosage simvastatin treatment
      affects the progression of experimental scrapie, and supports the concept that
      statin treatment may influence the prion pathogenesis.

PMID- 17496808
TI  - The effect of viewing graspable objects and actions in Parkinson's disease.
AB  - Viewing action-relevant stimuli such as a graspable object or another person
      moving can affect the observer's own motor system. Evidence exists that external
      stimuli may facilitate or hinder movement in Parkinson's disease, so we
      investigated whether action-relevant stimuli would exert a stronger influence. We
      measured the effect of action-relevant stimuli (graspable door handles and finger
      movements) on reaction times compared with baseline stimuli (bars and object
      movements). Parkinson's patients were influenced by the location of the baseline
      stimuli, but unlike healthy controls, action-relevant stimuli did not exert a
      stronger influence. This suggests that external cues exert their influence in
      Parkinson's disease through lower-level visual processes and the influence of
      action-relevant stimuli on the motor system is disrupted.

PMID- 17496809
TI  - The synaptic scaffolding protein Delphilin interacts with monocarboxylate
      transporter 2.
AB  - Delphilin, which interacts with a glutamate receptor (GluR) delta2-subunit, is a
      postsynaptic density scaffolding protein at the cerebellar parallel fiber
      Purkinje cell synapses. Delphilin specifically interacts with the GluRdelta2 C
      terminus via its postsynaptic density-95/discs-large/ZO-1 (PDZ) domain. As a
      number of PDZ-containing scaffolding proteins bind to several membrane proteins,
      we expected that Delphilin might also have other binding partners besides
      GluRdelta2. To search for the link between Delphilin and other binding proteins,
      we carried out screening among candidate membrane proteins localized in Purkinje
      cells by surface plasmon resonance analyses. As a result, we found that the C
      terminus of the monocarboxylate transporter 2 binds specifically and
      significantly with Delphilin PDZ and there is a probable existence of GluRdelta2
      Delphilin-monocarboxylate transporter 2 complex in synaptic membranes.

PMID- 17496810
TI  - Interleukin-1ra inhibits Fos expression and hyperalgesia in rats.
AB  - It is known that interleukin-1beta facilitates pain, but the mechanisms of this
      are not understood. This study investigated the role of interleukin-1beta in the
      expression of Fos, a marker of neuronal activation, and hyperalgesia caused by
      injecting complete Freund's adjuvant into one hind paw of the rat. Interleukin
      receptor antagonist (interleukin-1ra, 0.005 mg/rat) was given intrathecally
      twice, 24 h before complete Freund's adjuvant and immediately before complete
      Freund's adjuvant injection, to block interleukin-1beta action. Fos expression
      was measured 2 h after complete Freund's adjuvant injection. Paw withdrawal
      latency was used to assess hyperalgesia. The findings were that interleukin-1ra
      inhibited inflammation-induced Fos expression and hyperalgesia, which suggests
      that endogenous interleukin-1beta facilitates transmission of noxious messages at
      the spinal level by processes involving an enhanced Fos expression.

PMID- 17496812
TI  - Activation of right insular cortex during imaginary speech articulation.
AB  - Human speech articulation is a complex process controlled by a form of
      'programming' implemented in the brain. Analysis of speech articulation using
      neuroimaging techniques is difficult, however, because motor noise is time-locked
      to the articulatory events. The current magnetoencephalography study, in which 12
      participants were required to imagine vocalizing a phonogram after a visual cue,
      was designed to visualize the prearticulatory 'automatic' processes corresponding
      to the motor initiation. Magnetic activity correlating with the preparation for
      articulation occurred in the insular cortices at about 160 ms after the visual
      cue, and had a relative dominance in the right hemisphere. This suggests that
      motor control of speech proceeds from the insular regions, although the
      'automatic' nature of our task might have led to the observed right-sided
      dominance.

PMID- 17496811
TI  - Intraventricular ghrelin activates oxytocin neurons: implications in feeding
      behavior.
AB  - Ghrelin affects behavioral and physiological responses, such as feeding or the
      activity of the HPA axis. Distribution of its receptor in central sites involved
      in neuroendocrine control, including the hypothalamic paraventricular nucleus,
      indicates that interplay with multiple neuropeptidergic systems underlies
      ghrelin's actions. We report that intracerebroventricular ghrelin increases c-Fos
      immunoreactivity of oxytocin neurons in magno and parvocellular portions of the
      paraventricular nucleus. The orexigenic response to ghrelin administered at the
      dose that activates oxytocin neurons can be further elevated by pretreatment with
      a selective oxytocin receptor antagonist. Our data suggest that oxytocin may be
      responsible for the mediation of some effects induced by ghrelin. Modifications
      in the activity of the oxytocin system may alter some of these effects.

PMID- 17496813
TI  - Increased immunoreactivity of cdk5 activators in hippocampal sclerosis.
AB  - Cyclin-dependent kinase 5 is important in several in-vitro neurodegeneration
      paradigms. Whether cyclin-dependent kinase 5 contributes to cell death in human
      neurodegenerative diseases remains uncertain, particularly because post-mortem
      delay and other extrinsic factors might influence cyclin-dependent kinase 5
      activity. Here we demonstrate increased immunoreactivity for the activators of
      cyclin-dependent kinase 5 in post-mortem human hippocampi affected by the
      neurodegenerative condition hippocampal sclerosis, but not in histologically
      normal hippocampi. Moreover, in post-mortem brain tissue from patients with
      unilateral hippocampal sclerosis, increased immunoreactivity for cyclin-dependent
      kinase 5 activators was detected in the hippocampus with sclerosis, but not in
      the contralateral hippocampus, suggesting that extrinsic factors are unlikely to
      account for the differential staining observed. Our findings suggest that
      deregulation of cyclin-dependent kinase 5 might contribute to the pathogenesis of
      hippocampal sclerosis.

PMID- 17496814
TI  - Association study between the transferrin gene and schizophrenia in the Japanese
      population.
AB  - Several lines of evidence, including diffusion tensor imaging and microarray
      studies, indicate that abnormalities in myelination play an important role in the
      pathophysiology of schizophrenia. Of myelin and oligodendrocyte-related genes, a
      significant decrease in the mRNA levels of transferrin in schizophrenics has been
      reported by both microarray and quantitative polymerase chain reaction studies.
      We performed an association analysis of the transferrin gene in a Japanese
      population of 384 schizophrenic patients and 384 controls. Six single nucleotide
      polymorphisms were genotyped by polymerase chain reaction-restriction fragment
      length polymorphism and a TaqMan assay. No significant differences in genotype,
      allele, or haplotype frequencies of the six single nucleotide polymorphisms were
      observed between schizophrenic patients and controls. The present results suggest
      that the transferrin gene is not related to the development of schizophrenia in
      the Japanese population.

PMID- 17496815
TI  - Insulin resistance of hypothalamic arcuate neurons in neonatally overfed rats.
AB  - Rats exposed to early postnatal overfeeding by rearing in small litters become
      hyperphagic, hyperleptinemic, and hyperinsulinemic throughout later life. Medial
      arcuate neurons are involved in body weight regulation. They were tested in brain
      slices of control and small-litter rats concerning differences in responses to
      insulin. Insulin induced suppression of firing in controls, whereas in small
      litter rats inhibition was significantly reduced and activation increased. This
      could be observed in juvenile as well as adult rats. A gamma-aminobutyric acid
      type A receptor antagonist did not change the responses. Thus, negative feedback
      to the satiety signal insulin on medial arcuate neurons is reduced in neonatally
      overfed small-litter rats. This can be regarded as insulin resistance, which is
      induced during early development and persists in later life.

PMID- 17496816
TI  - Healthy student, healthy nurse: a stress management workshop.

PMID- 17496817
TI  - You've got mail: a new tool to help millennials prepare for the national council
      licensure examination.

PMID- 17496818
TI  - "Closet skeletons" that accompany all deanships.
AB  - Many new nursing leaders assuming deanships or assistant or interim deanships
      have limited education, experience, or background to prepare them for the job. To
      assist new deans and those aspiring to be deans, the authors of this department,
      2 deans, offer survival tips based on their personal experiences and insights.
      They address the common issues, challenges, and opportunities that academic
      executive teams face, such as negotiating an executive contract, obtaining
      faculty lines, building effective work teams, managing difficult employees, and
      creating nimble organizational structure to respond to changing consumer,
      healthcare delivery, and community needs. The authors welcome counterpoint
      discussions with readers.

PMID- 17496819
TI  - Elders as mentors of nursing students.

PMID- 17496820
TI  - Professional commitment in RN-BSN and basic BSN students: program evaluation.
AB  - This program evaluation study compared the outcome of professional commitment in
      RN-BSN, full-time basic, and part-time basic nursing students using the Health
      Care Professional Attitude Inventory. Students' responses did not differ on a
      pretest during the first course of the nursing major. Posttest professional
      commitment scores differed significantly. Faculty reviewed student performance
      and considered revising the evaluation plan of the undergraduate nursing program.

PMID- 17496821
TI  - Enhancing the ability of nursing students to perform a spiritual assessment.
AB  - According to the literature, a majority of nurses and nursing students report a
      lack of comfort and ability to perform a spiritual assessment. The researchers
      designed and implemented an intervention program to address the 4 barriers most
      frequently identified as obstacles to performing a spiritual assessment. They
      discuss this study and suggest teaching interventions to assist nursing students
      to assess and implement spiritual care. Researcher-developed tools are presented
      and can be made available for use.

PMID- 17496822
TI  - Evaluation of online and on-site options for master's degree and post-master's
      certificate programs.
AB  - Measures related to program evaluation were selected to compare on-site and
      online options of a master's and post-master's nursing program. Although some
      differences were found in student-related outcomes, the decision to continue the
      online options was based on program and organizational effectiveness. The decline
      in the number of on-site students has been offset by the expanding enrollments of
      online students and their national distribution. Increased costs were associated
      with offering online courses.

PMID- 17496823
TI  - Monitoring entry-level practice: keeping the national council licensure
      examination for registered nurses current.
AB  - The National Council Licensure Examination for Registered Nurses assesses whether
      a candidate has the ability to provide safe and effective nursing care upon entry
      into practice. It is essential that this assessment be current and relevant to
      nursing practice. The authors discuss methods that are used to provide evidence
      to support the 2007 NCLEX-RN Test Plan and to maintain the currency of the
      examination.

PMID- 17496824
TI  - Transforming student perspectives through reflective writing.
AB  - One of the primary goals of registered nurse-to-bachelor of science in nursing
      education is to help registered nurses see things in a new way or to transform
      their perspective. A package of 4 commonly used reflective writing activities
      used before, during, and after class is described as it is used for perspective
      transformation. This learning package goal is to push registered nurse-to
      bachelor of science in nursing students in their first course to consider new
      ways of thinking about their practice and their education.

PMID- 17496827
TI  - Effect of fatigue, workload, and environment on patient safety in the pediatric
      intensive care unit.
AB  - INTRODUCTION: Pediatric intensive care unit patient care occurs in an
      unpredictable, technology-rich environment that is dependent on highly skilled
      providers who need constant communication-all features providing the setting for
      potential error. This review examines basic principles of human error and sleep
      physiology and evaluates the evidence for potential effects of fatigued
      healthcare workers and workload on medical error. BODY: The pediatric intensive
      care unit setting, examined from a human factors engineering standpoint, is a
      highly complex environment in which fatigue and excessive workload can provide
      potential "holes" that may allow errors to occur. A large body of evidence is
      examined that suggests sleep deprivation can impair medical and surgical
      performance and can be improved with scheduling intervention. Nursing fatigue and
      workload have documented effects on increasing intensive care unit error,
      infections, and cost. Specific environmental factors such as distractions and
      communication barriers are also associated with greater error. CONCLUSION:
      Fatigue, excessive workload, and the pediatric intensive care unit environment
      can adversely affect the performance of physicians and nurses working in the
      pediatric intensive care unit. The weight of the evidence suggests that these
      factors have the potential to contribute to medical error in the pediatric
      intensive care unit.

PMID- 17496825
TI  - Multicultural healthcare: a transatlantic project.
AB  - Healthcare is increasingly multicultural, posing a challenge for nurse educators
      in both Europe and the United States. Nursing education faculties are responding
      to the challenge of internationalization, for instance, by participating in
      international student exchange projects to foster students' intercultural
      competence. The authors describe an educational model constructed during a
      transatlantic project between European and American universities. The benefits of
      the project from the Finnish partner's perspective are also reported.

PMID- 17496828
TI  - Electronic medical record, error detection, and error reduction: a pediatric
      critical care perspective.
AB  - INTRODUCTION: Automated extraction of data from computer-based medical records
      for use in quality improvement has been described for >20 yrs. OBJECTIVE: This
      article reviews the role of the electronic medical record in automating adverse
      event detection in the study of medication errors, nosocomial infection, and in
      the perioperative setting. In addition, the use of the electronic medical record
      in the detection and reduction of delays in STAT (at once) radiology testing and
      respiratory therapy treatment will be reviewed. CONCLUSION: The electronic
      medical record, including computerized provider order entry, can have an
      important effect on medical error detection and reduction.

PMID- 17496829
TI  - Nosocomial infections in the pediatric intensive care unit: affecting the impact
      on safety and outcome.
AB  - OBJECTIVE: To define the most common types of nosocomial infections in critically
      ill children and to summarize the effect of methods to reduce their prevalence.
      DESIGN: Review of published literature. RESULTS: While in the pediatric intensive
      care unit, 16% of children develop a nosocomial infection. Processes affecting
      modifiable factors of care can reduce the prevalence of hospital-acquired
      infections. CONCLUSIONS: The occurrence of a nosocomial infection represents
      failure and is not an acceptable outcome of treating critically ill children.
      Evidence-based process improvement can lead to significant reductions in hospital
      acquired infections in children. Most of the processes and practices discussed
      are not novel or intriguing but, when performed routinely and appropriately, can
      lead to reductions in hospital-acquired infections.

PMID- 17496830
TI  - Determining pediatric intensive care unit quality indicators for measuring
      pediatric intensive care unit safety.
AB  - INTRODUCTION: The measurement of quality and patient safety continues to gain
      increasing importance, as these measures are used for both healthcare improvement
      and accountability. Pediatric care, particularly that provided in pediatric
      intensive care units, is sufficiently different from adult care that specific
      metrics are required. BODY: Pediatric critical care requires specific measures
      for both quality and safety. Factors that may affect measures are identified,
      including data sources, risk adjustment, intended use, reliability, validity, and
      the usability of measures. The 18-month process to develop seven pediatric
      critical care measures proposed for national use is described. Specific patient
      safety metrics that can be applied to pediatric intensive care units include
      error-, injury-, and risk-based approaches. CONCLUSION: Measurement of pediatric
      critical care quality and safety will likely continue to evolve. Opportunities
      exist for intensivists to contribute and lead in the development and refinement
      of measures.

PMID- 17496831
TI  - Disclosure of medical error: is it worth the risk?
AB  - INTRODUCTION: The climate within the United States is rapidly changing with
      respect to patient and family knowledge of medical error and their expectations
      of the events that should occur after an error. OBJECTIVE: This article examines
      the history and changing tide of medical error disclosure, reviews the limited
      but growing body of literature surrounding patient and physician attitudes toward
      disclosing and discussing medical error, makes suggestions on what and how to
      disclose to patients and families that an error has occurred, and finally,
      discusses the effect of error disclosure. CONCLUSION: It seems that if disclosure
      of medical error is made with compassion, in a timely manner, and with good
      communication skills both during and after the disclosure process, patients and
      their families are at least no more likely to seek legal action and some lawsuits
      may actually be avoided.

PMID- 17496832
TI  - Sheddases and intramembrane-cleaving proteases: RIPpers of the membrane.
      Symposium on regulated intramembrane proteolysis.

PMID- 17496833
TI  - Transport of the leaderless protein Ku on the cell surface of activated monocytes
      regulates their migratory abilities.
AB  - Recent evidence shows that the DNA repair protein Ku is expressed on the surface
      of a subset of cells, where it contributes to adhesion and invasion processes,
      and also to viral or bacterial entry into target cells. Here, we show that Ku was
      expressed on the cell surface during activation of human monocytes and that its
      expression was independent of the conventional endoplasmic reticulum (ER)/Golgi
      secretory pathway. Ku inhibition, by blocking antibodies, decreases the migration
      of monocytes on fibronectin and laminin. On activation, nuclear Ku seems to move
      to the periphery of the cell and it shows a punctuate staining in the cytoplasm.
      The cytoplasmic distribution of Ku was shown to be unaltered by brefeldin A.
      Protease protection experiments show that Ku is contained within vesicles in
      activated monocytes. These data support a new role for Ku in the migration of
      monocytes into tissues, which depends on a tightly regulated pathway of
      intracellular redistribution.

PMID- 17496834
TI  - It is all about motivation.

PMID- 17496835
TI  - Fluoride allergy.

PMID- 17496836
TI  - Keep it simple.

PMID- 17496837
TI  - Too late?

PMID- 17496838
TI  - Maintaining values.

PMID- 17496839
TI  - Unreasonable CPD.

PMID- 17496840
TI  - Restorative nomenclature.

PMID- 17496841
TI  - Double teeth.

PMID- 17496842
TI  - Learn these lessons.

PMID- 17496843
TI  - Therapy myths.

PMID- 17496844
TI  - News accountability.

PMID- 17496845
TI  - Inadequate education.

PMID- 17496846
TI  - Orthodontic restrictions.

PMID- 17496847
TI  - Drawn into the backwash.

PMID- 17496848
TI  - Lost in the system.

PMID- 17496860
TI  - Malocclusion--a term in need of dropping or redefinition?
AB  - I believe the time is coming when we should consider dropping the term
      'malocclusion'. In its present meaning it is too mechanical and misrepresents the
      fundamental fact that an occlusion can only be judged against the tissue
      reactions to it or the patient's assessment of it.

PMID- 17496861
TI  - Laser regulation and safety in general dental practice.
AB  - Laser devices, instruments and machines vary in their potential for light energy
      emission from low-powered hand-held or integrated devices, to high-powered units
      capable of cutting and ablating tissue and materials. The safe use of lasers in
      dentistry extends to all personnel who might be exposed, either deliberately or
      by accident, and demands of the lead clinician an approach to their use in order
      that risk of accidental exposure to laser light is minimised. The scope for
      regulations extends in similar ways to those imposed on the use of ionising
      radiation in the dental practice. Laser safety measures in the dental surgery are
      often drawn from the safe approach to the use of lasers in general and other
      specialties in medicine and surgery. This article serves to examine the risks
      involved in laser use in dentistry, the regulations governing safe use and the
      responsibilities of personnel involved in providing treatment to patients.

PMID- 17496862
TI  - Introduction to the world wide web.
AB  - The World Wide Web used to be nicknamed the 'World Wide Wait'. Now, thanks to
      high speed broadband connections, browsing the web has become a much more
      enjoyable and productive activity. Computers need to know where web pages are
      stored on the Internet, in just the same way as we need to know where someone
      lives in order to post them a letter. This section explains how the World Wide
      Web works and how web pages can be viewed using a web browser.

PMID- 17496863
TI  - Change in cardiovascular risk status after dental clearance.
AB  - There is considerable debate over the relationship between periodontal and
      cardiovascular disease. It has been postulated that inflammatory mediators
      prevalent in periodontal disease may impact on atheroma formation and the
      thrombotic process. In cross-sectional, observational studies, periodontitis is
      associated with elevated C-reactive protein (CRP), hyperfibrinogenaemia and
      moderate leukocytosis. CRP levels have also been shown to decrease following
      periodontal therapy. CRP is a reliable marker of the acute phase reaction to
      infections and/or inflammation and is a powerful predictor of future coronary
      events.

PMID- 17496870
TI  - Review: the use of sodium hypochlorite in endodontics--potential complications
      and their management.
AB  - Aqueous sodium hypochlorite (bleach) solution is widely used in dental practice
      during root canal treatment. Although it is generally regarded as being very
      safe, potentially severe complications can occur when it comes into contact with
      soft tissue. This paper discusses the use of sodium hypochlorite in dental
      treatment, reviews the current literature regarding hypochlorite complications,
      and considers the appropriate management for a dental practitioner when faced
      with a potentially adverse incident with this agent.

PMID- 17496886
TI  - Management of periodontal diseases within the NHS three years on: are things any
      better?
AB  - This paper will begin by briefly analysing the provision of periodontal care
      under the old and new contracts and introduce the concept of medical management
      formulas under the 'wellness model' rather than the traditional surgical approach
      that comprises the 'repair model'. A new online risk (and disease) calculator
      'PreViser' developed in the United States and now available in the UK
      (Previser.co.uk) will be presented as an example of how UK Dentists can start
      working towards adopting the wellness model in modern preventative care
      practices. The presentation will then discuss the myths and realities surrounding
      one-stage full mouth disinfection, and ask how strong the evidence is for
      benefit, before taking a look into the future of novel host-modulation therapies
      and demonstrating how we can control what our genes do by what we eat!

PMID- 17496887
TI  - p73 supports cellular growth through c-Jun-dependent AP-1 transactivation.
AB  - The cause or consequence of overexpression of p73 (refs 1, 2), the structural and
      functional homologue of the tumour-suppressor gene product p53 (refs 3, 4), in
      human cancers is poorly understood. Here, we report a role for p73 in supporting
      cellular growth through the upregulation of AP-1 transcriptional activity. p73
      suppresses growth when overexpressed alone, but synergises with the proto
      oncogene c-Jun to promote cellular survival. Conversely, silencing of p73
      expression compromises cellular proliferation. Molecular analysis revealed that
      expression of the AP-1 target-gene product cyclinD1 (ref. 5) is reduced
      concomitant with p73, but not p53, silencing. Moreover, cyclinD1 was induced by
      p73 expression in a c-Jun-dependent manner, and was required for p73-mediated
      cell survival. Furthermore, c-Jun-dependent AP-1 transcriptional activity was
      augmented by p73 and, consistently, induction of endogenous AP-1 target genes was
      compromised in the absence of p73. Chromatin immunoprecipitation and
      electrophoretic mobility shift analysis indicated that p73 enhanced the binding
      of phosphorylated c-Jun and Fra-1, another AP-1 family member, to AP-1 consensus
      DNA sequences, by regulating c-Jun phosphorylation and Fra-1 expression.
      Collectively, our data demonstrates a novel and unexpected role of p73 in
      augmenting AP-1 transcriptional activity through which it supports cellular
      growth.

PMID- 17496888
TI  - Diarylquinolines target subunit c of mycobacterial ATP synthase.
AB  - The diarylquinoline R207910 (TMC207) is a promising candidate in clinical
      development for the treatment of tuberculosis. Though R207910-resistant
      mycobacteria bear mutations in ATP synthase, the compound's precise target is not
      known. Here we establish by genetic, biochemical and binding assays that the
      oligomeric subunit c (AtpE) of ATP synthase is the target of R207910. Thus
      targeting energy metabolism is a new, promising approach for antibacterial drug
      discovery.

PMID- 17496889
TI  - Probing the dynamics of O-GlcNAc glycosylation in the brain using quantitative
      proteomics.
AB  - The addition of the monosaccharide beta-N-acetyl-D-glucosamine to proteins (O
      GlcNAc glycosylation) is an intracellular, post-translational modification that
      shares features with phosphorylation. Understanding the cellular mechanisms and
      signaling pathways that regulate O-GlcNAc glycosylation has been challenging
      because of the difficulty of detecting and quantifying the modification. Here, we
      describe a new strategy for monitoring the dynamics of O-GlcNAc glycosylation
      using quantitative mass spectrometry-based proteomics. Our method, which we have
      termed quantitative isotopic and chemoenzymatic tagging (QUIC-Tag), combines
      selective, chemoenzymatic tagging of O-GlcNAc proteins with an efficient isotopic
      labeling strategy. Using the method, we detect changes in O-GlcNAc glycosylation
      on several proteins involved in the regulation of transcription and mRNA
      translocation. We also provide the first evidence that O-GlcNAc glycosylation is
      dynamically modulated by excitatory stimulation of the brain in vivo. Finally, we
      use electron-transfer dissociation mass spectrometry to identify exact sites of O
      GlcNAc modification. Together, our studies suggest that O-GlcNAc glycosylation
      occurs reversibly in neurons and, akin to phosphorylation, may have important
      roles in mediating the communication between neurons.

PMID- 17496890
TI  - RIM1 confers sustained activity and neurotransmitter vesicle anchoring to
      presynaptic Ca2+ channels.
AB  - The molecular organization of presynaptic active zones is important for the
      neurotransmitter release that is triggered by depolarization-induced Ca2+ influx.
      Here, we demonstrate a previously unknown interaction between two components of
      the presynaptic active zone, RIM1 and voltage-dependent Ca2+ channels (VDCCs),
      that controls neurotransmitter release in mammalian neurons. RIM1 associated with
      VDCC beta-subunits via its C terminus to markedly suppress voltage-dependent
      inactivation among different neuronal VDCCs. Consistently, in pheochromocytoma
      neuroendocrine PC12 cells, acetylcholine release was significantly potentiated by
      the full-length and C-terminal RIM1 constructs, but membrane docking of vesicles
      was enhanced only by the full-length RIM1. The beta construct beta-AID dominant
      negative, which disrupts the RIM1-beta association, accelerated the inactivation
      of native VDCC currents, suppressed vesicle docking and acetylcholine release in
      PC12 cells, and inhibited glutamate release in cultured cerebellar neurons. Thus,
      RIM1 association with beta in the presynaptic active zone supports release via
      two distinct mechanisms: sustaining Ca2+ influx through inhibition of channel
      inactivation, and anchoring neurotransmitter-containing vesicles in the vicinity
      of VDCCs.

PMID- 17496891
TI  - The dynamics of memory as a consequence of optimal adaptation to a changing body.
AB  - There are many causes for variation in the responses of the motor apparatus to
      neural commands. Fast-timescale disturbances occur when muscles fatigue. Slow
      timescale disturbances occur when muscles are damaged or when limb dynamics
      change as a result of development. To maintain performance, motor commands need
      to adapt. Computing the best adaptation in response to any performance error
      results in a credit assignment problem: which timescale is responsible for this
      disturbance? Here we show that a Bayesian solution to this problem accounts for
      numerous behaviors of animals during both short- and long-term training. Our
      analysis focused on characteristics of the oculomotor system during learning,
      including the effects of time passage. However, we suggest that learning and
      memory in other paradigms, such as reach adaptation, adaptation of visual neurons
      and retrieval of declarative memories, largely follow similar rules.

PMID- 17496892
TI  - Variation in FTO contributes to childhood obesity and severe adult obesity.
AB  - We identified a set of SNPs in the first intron of the FTO (fat mass and obesity
      associated) gene on chromosome 16q12.2 that is consistently strongly associated
      with early-onset and severe obesity in both adults and children of European
      ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected
      individuals and 5,100 controls. The at-risk haplotype yields a proportion of
      attributable risk of 22% for common obesity. We conclude that FTO contributes to
      human obesity and hence may be a target for subsequent functional analyses.

PMID- 17496893
TI  - Root tip contact with low-phosphate media reprograms plant root architecture.
AB  - Plant roots are able to sense soil nutrient availability. In order to acquire
      heterogeneously distributed water and minerals, they optimize their root
      architecture. One poorly understood plant response to soil phosphate (P(i))
      deficiency is a reduction in primary root growth with an increase in the number
      and length of lateral roots. Here we show that physical contact of the
      Arabidopsis thaliana primary root tip with low-P(i) medium is necessary and
      sufficient to arrest root growth. We further show that loss-of-function mutations
      in Low Phosphate Root1 (LPR1) and its close paralog LPR2 strongly reduce this
      inhibition. LPR1 was previously mapped as a major quantitative trait locus (QTL);
      the molecular origin of this QTL is explained by the differential allelic
      expression of LPR1 in the root cap. These results provide strong evidence for the
      involvement of the root cap in sensing nutrient deficiency, responding to it, or
      both. LPR1 and LPR2 encode multicopper oxidases (MCOs), highlighting the
      essential role of MCOs for plant development.

PMID- 17496894
TI  - Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1.
AB  - Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell
      expression patterns and inhibitory capacity upon binding to their ligands, HLA-B
      Bw4 molecules, present on target cells. Using a sample size of over 1,500 human
      immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic
      combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence
      both AIDS progression and plasma HIV RNA abundance in a consistent manner. These
      genetic data correlate very well with previously defined functional differences
      that distinguish KIR3DL1 allotypes. The various epistatic effects observed here
      for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with
      regard to any pair of genetic loci in human disease, and indicate that NK cells
      may have a critical role in the natural history of HIV infection.

PMID- 17496895
TI  - Cell surface 4-1BBL mediates sequential signaling pathways 'downstream' of TLR
      and is required for sustained TNF production in macrophages.
AB  - The stimulation of Toll-like receptors (TLRs) on macrophages triggers production
      of the cytokine tumor necrosis factor (TNF). TNF production occurs within 1 h of
      TLR stimulation and is sustained for 1 d. Here we document a function for the TNF
      family member 4-1BB ligand (4-1BBL) in sustaining TLR-induced TNF production. TLR
      signaling induced 4-1BBL, and 4-1BBL interacted with TLRs on the macrophage
      surface. The influence of 4-1BBL on TNF production was independent of its
      receptor (4-1BB) and did not require the adaptors MyD88 or TRIF. It did not
      influence TLR4-induced activation of transcription factor NF-kappaB (an early
      response) but was required for TLR4-induced activation of transcription factors
      CREB and C/EBP (a late event). Transient TLR4-MyD88 complexes appeared during the
      first hour after lipopolysaccharide stimulation, and TLR4-4-1BBL interactions
      were detected between 2 h and 8 h after lipopolysaccharide stimulation. Our
      results indicate that two different TLR4 complexes sequentially form and
      selectively control early and late TNF production.

PMID- 17496896
TI  - Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype
      triggering Rho-GTPase activity required for HIV-1 replication.
AB  - DC-SIGN, a C-type lectin expressed on dendritic cells (DCs), can sequester human
      immunodeficiency virus (HIV) virions in multivesicular bodies. Here, using large
      scale gene expression profiling and tyrosine-phosphorylated proteome analyses, we
      characterized signaling mediated by DC-SIGN after activation by either HIV or a
      DC-SIGN-specific antibody. Activation of DC-SIGN resulted in downregulation of
      genes encoding major histocompatibility complex class II, Jagged 1 and interferon
      response molecules and upregulation of the gene encoding transcription factor
      ATF3. Phosphorylated proteome analysis showed that HIV- or antibody-stimulated DC
      SIGN signaling was mediated by the Rho guanine nucleotide-exchange factor LARG
      and led to increased Rho-GTPase activity. Activation of LARG in DCs exposed to
      HIV was required for the formation of virus-T cell synapses. Thus, HIV
      sequestration by and stimulation of DC-SIGN helps HIV evade immune responses and
      spread to cells.

PMID- 17496897
TI  - Metallated conjugated polymers as a new avenue towards high-efficiency polymer
      solar cells.
AB  - Bulk heterojunction solar cells have been extensively studied owing to their
      great potential for cost-effective photovoltaic devices. Although recent advances
      resulted in the fabrication of poly(3-hexylthiophene) (P3HT)/fullerene derivative
      based solar cells with efficiencies in the range 4.4-5.0%, theoretical
      calculations predict that the development of novel donor materials with a lower
      bandgap is required to exceed the power-conversion efficiency of 10%. However,
      all of the lower bandgap polymers developed so far have failed to reach the
      efficiency of P3HT-based cells. To address this issue, we synthesized a soluble,
      intensely coloured platinum metallopolyyne with a low bandgap of 1.85 eV. The
      solar cells, containing metallopolyyne/fullerene derivative blends as the
      photoactive material, showed a power-conversion efficiency with an average of
      4.1%, without annealing or the use of spacer layers needed to achieve comparable
      efficiency with P3HT. This clearly demonstrates the potential of metallated
      conjugated polymers for efficient photovoltaic devices.

PMID- 17496898
TI  - Microgram-scale protein structure determination by NMR.
AB  - Using conventional triple-resonance nuclear magnetic resonance (NMR) experiments
      with a 1 mm triple-resonance microcoil NMR probe, we determined near complete
      resonance assignments and three-dimensional (3D) structure of the 68-residue
      Methanosarcina mazei TRAM protein using only 72 mug (6 microl, 1.4 mM) of
      protein. This first example of a complete solution NMR structure determined using
      microgram quantities of protein demonstrates the utility of microcoil-probe NMR
      technologies for protein samples that can be produced in only limited quantities.

PMID- 17496899
TI  - Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental
      cerebral malaria.
AB  - Cerebral malaria claims more than 1 million lives per year. We report that heme
      oxygenase-1 (HO-1, encoded by Hmox1) prevents the development of experimental
      cerebral malaria (ECM). BALB/c mice infected with Plasmodium berghei ANKA
      upregulated HO-1 expression and activity and did not develop ECM. Deletion of
      Hmox1 and inhibition of HO activity increased ECM incidence to 83% and 78%,
      respectively. HO-1 upregulation was lower in infected C57BL/6 compared to BALB/c
      mice, and all infected C57BL/6 mice developed ECM (100% incidence).
      Pharmacological induction of HO-1 and exposure to the end-product of HO-1
      activity, carbon monoxide (CO), reduced ECM incidence in C57BL/6 mice to 10% and
      0%, respectively. Whereas neither HO-1 nor CO affected parasitemia, both
      prevented blood-brain barrier (BBB) disruption, brain microvasculature congestion
      and neuroinflammation, including CD8(+) T-cell brain sequestration. These effects
      were mediated by the binding of CO to hemoglobin, preventing hemoglobin oxidation
      and the generation of free heme, a molecule that triggers ECM pathogenesis.

PMID- 17496900
TI  - TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and
      inhibited by IL-27/STAT1.
AB  - T-helper type 17 cells (T(H)17) are implicated in rodent models of immune
      mediated diseases. Here we report their involvement in human uveitis and
      scleritis, and validate our findings in experimental autoimmune uveoretinitis
      (EAU), a model of uveitis. T(H)17 cells were present in human peripheral blood
      mononuclear cells (PBMC), and were expanded by interleukin (IL)-2 and inhibited
      by interferon (IFN)-gamma. Their numbers increased during active uveitis and
      scleritis and decreased following treatment. IL-17 was elevated in EAU and
      upregulated tumor necrosis factor (TNF)-alpha in retinal cells, suggesting a
      mechanism by which T(H)17 may contribute to ocular pathology. Furthermore, IL-27
      was constitutively expressed in retinal ganglion and photoreceptor cells, was
      upregulated by IFN-gamma and inhibited proliferation of T(H)17. These findings
      suggest that T(H)1 cells may mitigate uveitis by antagonizing the T(H)17
      phenotype through the IFN-gamma-mediated induction of IL-27 in target tissue. The
      finding that IL-2 promotes T(H)17 expansion provides explanations for the
      efficacy of IL-2R antibody therapy in uveitis, and suggests that antagonism of
      T(H)17 by IFN-gamma and/or IL-27 could be used for the treatment of chronic
      inflammation.

PMID- 17496901
TI  - The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas.
AB  - We analyzed the PI3K-AKT signaling cascade in a cohort of sarcomas and found a
      marked induction of insulin receptor substrate-2 (IRS2) and phosphorylated AKT
      and a concomitant upregulation of downstream effectors in most leiomyosarcomas.
      To determine the role of aberrant PI3K-AKT signaling in leiomyosarcoma
      pathogenesis, we genetically inactivated Pten in the smooth muscle cell lineage
      by cross-breeding Pten(loxP/loxP) mice with Tagln-cre mice. Mice carrying
      homozygous deletion of Pten alleles developed widespread smooth muscle cell
      hyperplasia and abdominal leiomyosarcomas, with a very rapid onset and elevated
      incidence (approximately 80%) compared to other animal models. Constitutive mTOR
      activation was restricted to the leiomyosarcomas, revealing the requirement for
      additional molecular events besides Pten loss. The rapamycin derivative
      everolimus substantially decelerated tumor growth on Tagln-cre/Pten(loxP/loxP)
      mice and prolonged their lifespan. Our data show a new and critical role for the
      AKT-mTOR pathway in smooth muscle transformation and leiomyosarcoma genesis, and
      support treatment of selected sarcomas by the targeting of this pathway with new
      compounds or combinations of these with conventional chemotherapy agents.

PMID- 17496902
TI  - Mechanism for expanding the decoding capacity of transfer RNAs by modification of
      uridines.
AB  - One of the most prevalent base modifications involved in decoding is uridine 5
      oxyacetic acid at the wobble position of tRNA. It has been known for several
      decades that this modification enables a single tRNA to decode all four codons in
      a degenerate codon box. We have determined structures of an anticodon stem-loop
      of tRNA(Val) containing the modified uridine with all four valine codons in the
      decoding site of the 30S ribosomal subunit. An intramolecular hydrogen bond
      involving the modification helps to prestructure the anticodon loop. We found
      unusual base pairs with the three noncomplementary codon bases, including a G.U
      base pair in standard Watson-Crick geometry, which presumably involves an enol
      form for the uridine. These structures suggest how a modification in the uridine
      at the wobble position can expand the decoding capability of a tRNA.

PMID- 17496903
TI  - Swi3p controls SWI/SNF assembly and ATP-dependent H2A-H2B displacement.
AB  - Yeast SWI/SNF is a multisubunit, 1.14-MDa ATP-dependent chromatin-remodeling
      enzyme required for transcription of a subset of inducible genes. Biochemical
      studies have demonstrated that SWI/SNF uses the energy from ATP hydrolysis to
      generate superhelical torsion, mobilize mononucleosomes, enhance the
      accessibility of nucleosomal DNA and remove H2A-H2B dimers from mononucleosomes.
      Here we describe the ATP-dependent activities of a SWI/SNF sub complex that is
      composed of only three subunits, Swi2p, Arp7p and Arp9p. Whereas this sub complex
      is fully functional in most remodeling assays, Swi2p-Arp7p-Arp9p is defective for
      ATP-dependent removal of H2A-H2B dimers. We identify the acidic N terminus of the
      Swi3p subunit as a novel H2A-H2B-binding domain required for ATP-dependent dimer
      loss. Our data indicate that H2A-H2B dimer loss is not an obligatory consequence
      of ATP-dependent DNA translocation, and furthermore they suggest that SWI/SNF is
      composed of at least four interdependent modules.

PMID- 17496904
TI  - Expression of matrix metalloproteinases MMP-2 and MMP-9 is altered during
      nephrogenesis in fetuses from diabetic rats.
AB  - Remodeling of extracellular matrix (ECM) is an important physiological feature of
      normal growth and development. Recent studies have emphasized the role of matrix
      metalloproteinases (MMP-2 and MMP-9) in normal mouse nephrogenesis. We have
      demonstrated previously in the rat that in utero exposure to maternal diabetes
      impairs renal development leading to a 30% reduction in the nephron number.
      Transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor
      (CTGF) are known to mediate high glucose effects on matrix degradation. The aim
      of the present study was to address the expression of type IV collagenase and TGF
      beta1/CTGF systems in rat kidney during normal development and after in utero
      exposure to maternal diabetes. Both MMP-2 and MMP-9 mRNA metanephric expressions
      and activities were dramatically downregulated in kidneys issued from diabetic
      fetuses and in metanephros cultured in the presence of high glucose
      concentration. TGF-beta1 and CTGF expressions were significantly enhanced in
      diabetic fetal kidneys and in high glucose cultured metanephroi. Conditioned
      media obtained from metanephroi grown with high glucose concentration upregulated
      functional TGF-beta activity in transfected ATDC5 cells. In conclusion, in
      impaired nephrogenesis resulting from in utero exposure to maternal diabetes,
      alteration of both type IV collagenase and TGF-beta1/CTGF systems may lead to
      abnormal remodeling of ECM, which may, in turn, induce defects in ureteral bud
      branching leading to the observed reduction in the nephron number with
      consequences later in life: progression of chronic renal disease and
      hypertension.

PMID- 17496905
TI  - Alteration of beta-secretase traffic by the receptor tyrosine kinase signaling
      pathway - a new mechanism for regulating Alzheimer's beta-amyloid production.

PMID- 17496906
TI  - PAT: waking up a lazy sleeping beauty.

PMID- 17496908
TI  - MAPKs: function, regulation, role in cancer and therapeutic targeting.

PMID- 17496909
TI  - Differential regulation and properties of MAPKs.
AB  - Mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs
      including embryogenesis, proliferation, differentiation and apoptosis based on
      cues derived from the cell surface and the metabolic state and environment of the
      cell. In mammals, there are more than a dozen MAPK genes. The best known are the
      extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase
      (JNK(1-3)) and p38(alpha, beta, gamma and delta) families. ERK3, ERK5 and ERK7
      are other MAPKs that have distinct regulation and functions. MAPK cascades
      consist of a core of three protein kinases. Despite the apparently simple
      architecture of this pathway, these enzymes are capable of responding to a
      bewildering number of stimuli to produce exquisitely specific cellular outcomes.
      These responses depend on the kinetics of their activation and inactivation, the
      subcellular localization of the kinases, the complexes in which they act, and the
      availability of substrates. Fine-tuning of cascade activity can occur through
      modulatory inputs to cascade component from the primary kinases to the
      scaffolding accessory proteins. Here, we describe some of the properties of the
      three major MAPK pathways and discuss how these properties govern pathway
      regulation and activity.

PMID- 17496910
TI  - Integrating signals from RTKs to ERK/MAPK.
AB  - Signals received at the cell surface must be properly transmitted to critical
      targets within the cell to achieve the appropriate biological response. This
      process of signal transduction is often initiated by receptor tyrosine kinases
      (RTKs), which function as entry points for many extracellular cues and play a
      critical role in recruiting the intracellular signaling cascades that orchestrate
      a particular response. Essential for most RTK-mediated signaling is the
      engagement and activation of the mitogen-activated protein kinase (MAPK) cascade
      comprised of the Raf, MEK and extracellular signal-regulated kinase (ERK)
      kinases. For many years, it was thought that signaling from RTKs to ERK occurred
      only at the plasma membrane and was mediated by a simple, linear Ras-dependent
      pathway. However, the limitation of this model became apparent with the discovery
      that Ras and ERK can be activated at various intracellular compartments, and that
      RTKs can modulate Ras/ERK signaling from these sites. Moreover, ERK scaffolding
      proteins and signaling modulators have been identified that play critical roles
      in determining the strength, duration and location of RTK-mediated ERK signaling.
      Together, these factors contribute to the diversity of biological responses
      generated by RTK signaling.

PMID- 17496911
TI  - G protein regulation of MAPK networks.
AB  - G proteins provide signal-coupling mechanisms to heptahelical cell surface
      receptors and are critically involved in the regulation of different mitogen
      activated protein kinase (MAPK) networks. The four classes of G proteins, defined
      by the G(s), G(i), G(q) and G(12) families, regulate ERK1/2, JNK, p38MAPK, ERK5
      and ERK6 modules by different mechanisms. The alpha- as well as betagamma
      subunits are involved in the regulation of these MAPK modules in a context
      specific manner. While the alpha- and betagamma-subunits primarily regulate the
      MAPK pathways via their respective effector-mediated signaling pathways, recent
      studies have unraveled several novel signaling intermediates including receptor
      tyrosine kinases and small GTPases through which these G-protein subunits
      positively as well as negatively regulate specific MAPK modules. Multiple
      mechanisms together with specific scaffold proteins that can link G-protein
      coupled receptors or G proteins to distinct MAPK modules contribute to the
      context-specific and spatio-temporal regulation of mitogen-activated protein
      signaling networks by G proteins.

PMID- 17496912
TI  - KSR and CNK: two scaffolds regulating RAS-mediated RAF activation.
AB  - The RAS-RAF-MEK-extracellular-regulated kinase (RAS/ERK) pathway is a major
      intracellular route used by metazoan cells to channel to downstream targets a
      diverse array of signals, including those controlling cell proliferation and
      survival. Recent findings suggest that the pathway is assembled by specific
      scaffolding proteins that in turn regulate the efficiency, the location and/or
      the duration of signal transmission. Here, through the angle of studies conducted
      in Drosophila and C. elegans, we present two such proteins, the kinase suppressor
      of RAS (KSR) and connector enhancer of KSR (CNK) scaffolds, and highlight their
      implication in a novel mechanism regulating RAS-mediated RAF activation. Based on
      recent findings, we discuss the possibility that KSR, a RAF-like protein, does
      not solely act as a scaffold, but directly induces RAF catalytic function by a
      kinase-independent mechanism apparently shared by RAF-like proteins.

PMID- 17496913
TI  - Role of mitogen-activated protein kinase kinase kinases in signal integration.
AB  - Mitogen-activated protein kinases (MAPKs) are members of a dynamic protein kinase
      network through which diverse stimuli regulate the spatio-temporal activities of
      complex biological systems. MAPKs regulate critical cellular functions required
      for homeostasis such as the expression of cytokines and proteases, cell cycle
      progression, cell adherence, motility and metabolism. MAPKs therefore influence
      cell proliferation, differentiation, survival, apoptosis and development. In
      vertebrates, five MAPK families are regulated by MAPK kinase kinase-MAPK kinase
      MAPK (MKKK-MKK-MAPK) phosphorelay systems. There are at least 20 MKKKs that
      selectively phosphorylate and activate different combinations of the seven MKKs,
      resulting in a specific activation profile of members within the five MAPK
      families. MKKKs are differentially activated by upstream stimuli including
      cytokines, antigens, toxins and stress insults providing a mechanism to integrate
      the activation of different MAPKs with the cellular response to each stimulus.
      Thus, MKKKs can be considered as 'signaling hubs' that regulate the specificity
      of MAPK activation. In this review, we describe how the MKKK 'hub' function
      regulates the specificity of MAPK activation, highlighting MKKKs as targets for
      therapeutic intervention in cancer and other diseases.

PMID- 17496914
TI  - Role of mitogen-activated protein kinase kinase 4 in cancer.
AB  - Mitogen-activated protein (MAP) kinase kinase 4 (MKK4) is a component of stress
      activated MAP kinase signaling modules. It directly phosphorylates and activates
      the c-Jun N-terminal kinase (JNK) and p38 families of MAP kinases in response to
      environmental stress, pro-inflammatory cytokines and developmental cues. MKK4 is
      ubiquitously expressed and the targeted deletion of the Mkk4 gene in mice results
      in early embryonic lethality. Further studies in mice have indicated a role for
      MKK4 in liver formation, the immune system and cardiac hypertrophy. In humans, it
      is reported that loss of function mutations in the MKK4 gene are found in
      approximately 5% of tumors from a variety of tissues, suggesting it may have a
      tumor suppression function. Furthermore, MKK4 has been identified as a suppressor
      of metastasis of prostate and ovarian cancers. However, the role of MKK4 in
      cancer development appears complex as other studies support a pro-oncogenic role
      for MKK4 and JNK. Here we review the biochemical and functional properties of
      MKK4 and discuss the likely mechanisms by which it may regulate the steps leading
      to the formation of cancers.

PMID- 17496915
TI  - Scaffold proteins of MAP-kinase modules.
AB  - Mitogen-activated protein kinases (MAPKs) regulate critical signaling pathways
      involved in cell proliferation, differentiation and apoptosis. Recent studies
      have shown that a novel class of scaffold proteins mediates the structural and
      functional organization of the three-tier MAPK module. By linking the MAP3K,
      MAP2K and MAPK into a multienzyme complex, these MAPK-specific scaffold proteins
      provide an insulated physical conduit through which signals from the respective
      MAPK can be transmitted to the appropriate spatiotemporal cellular loci. Scaffold
      proteins play a determinant role in modulating the signaling strength of their
      cognate MAPK module by regulating the signal amplitude and duration. The scaffold
      proteins themselves are finely regulated resulting in dynamic intra- and inter
      molecular interactions that can modulate the signaling outputs of MAPK modules.
      This review focuses on defining the diverse mechanisms by which these scaffold
      proteins interact with their respective MAPK modules and the role of such
      interactions in the spatiotemporal organization as well as context-specific
      signaling of the different MAPK modules.

PMID- 17496916
TI  - Differential regulation of MAP kinase signalling by dual-specificity protein
      phosphatases.
AB  - The regulated dephosphorylation of mitogen-activated protein kinases (MAPKs)
      plays a key role in determining the magnitude and duration of kinase activation
      and hence the physiological outcome of signalling. In mammalian cells, an
      important component of this control is mediated by the differential expression
      and activities of a family of 10 dual-specificity (Thr/Tyr) MAPK phosphatases
      (MKPs). These enzymes share a common structure in which MAPK substrate
      recognition is determined by sequences within an amino-terminal non-catalytic
      domain whereas MAPK binding often leads to a conformational change within the C
      terminal catalytic domain resulting in increased enzyme activity. MKPs can either
      recognize and inactivate a single class of MAP kinase, as in the specific
      inactivation of extracellular signal regulated kinase (ERK) by the cytoplasmic
      phosphatase DUSP6/MKP-3 or can regulate more than one MAPK pathway as illustrated
      by the ability of DUSP1/MKP-1 to dephosphorylate ERK, c-Jun amino-terminal kinase
      and p38 in the cell nucleus. These properties, coupled with transcriptional
      regulation of MKP expression in response to stimuli that activate MAPK
      signalling, suggest a complex negative regulatory network in which individual
      MAPK activities can be subject to negative feedback control, but also raise the
      possibility that signalling through multiple MAPK pathways may be integrated at
      the level of regulation by MKPs.

PMID- 17496917
TI  - Ubiquitin-mediated activation of TAK1 and IKK.
AB  - Transforming growth factor beta activated kinase-1 (TAK1), a member of the
      mitogen-activated protein kinase kinase kinase family, has emerged as a key
      regulator of signal transduction cascades leading to the activation of the
      transcription factors nuclear factor-kappa B (NF-kappaB) and activator protein-1
      (AP-1). Stimulation of cells with cytokines and microbial pathogens results in
      the activation of TAK1, which subsequently activates the I-kappa B kinase complex
      (IKK) and mitogen-activated protein (MAP) kinases, culminating in the activation
      of NF-kappaB and AP-1, respectively. Recent studies have shown that
      polyubiquitination of signalling proteins through lysine (Lys)-63-linked
      polyubiquitin chains plays an important role in the activation of TAK1 and IKK.
      Unlike Lys-48-linked polyubiquitination, which normally targets proteins for
      degradation by the proteasome, Lys-63-linked polyubiquitin chains act as
      scaffolds to assemble protein kinase complexes and mediate their activation
      through proteasome-independent mechanisms. The concept of ubiquitin-mediated
      activation of protein kinases is supported by the discoveries of ubiquitination
      and deubiquitination enzymes as well as ubiquitin-binding proteins that function
      upstream of TAK1 and IKK. Recent biochemical and genetic studies provide further
      insights into the mechanism and function of ubiquitin signalling and these
      advances will be the focus of this review.

PMID- 17496918
TI  - The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the
      G1- to S-phase transition.
AB  - The Ras-dependent extracellular signal-regulated kinase (ERK)1/2 mitogen
      activated protein (MAP) kinase pathway plays a central role in cell proliferation
      control. In normal cells, sustained activation of ERK1/ERK2 is necessary for G1-
      to S-phase progression and is associated with induction of positive regulators of
      the cell cycle and inactivation of antiproliferative genes. In cells expressing
      activated Ras or Raf mutants, hyperactivation of the ERK1/2 pathway elicits cell
      cycle arrest by inducing the accumulation of cyclin-dependent kinase inhibitors.
      In this review, we discuss the mechanisms by which activated ERK1/ERK2 regulate
      growth and cell cycle progression of mammalian somatic cells. We also highlight
      the findings obtained from gene disruption studies.

PMID- 17496919
TI  - MAP kinases and the control of nuclear events.
AB  - The mitogen-activated protein kinases (MAPKs) are a family of serine/threonine
      kinases that play an essential role in signal transduction by modulating gene
      transcription in the nucleus in response to changes in the cellular environment.
      They include the extracellular signal-regulated protein kinases (ERK1 and ERK2);
      c-Jun N-terminal kinases (JNK1, JNK2, JNK3); p38s (p38alpha, p38beta, p38gamma,
      p38delta) and ERK5. The molecular events in which MAPKs function can be separated
      in discrete and yet interrelated steps: activation of the MAPK by their upstream
      kinases, changes in the subcellular localization of MAPKs, and recognition,
      binding and phosphorylation of MAPK downstream targets. The resulting pattern of
      gene expression will ultimately depend on the integration of the combinatorial
      signals provided by the temporal activation of each group of MAPKs. This review
      will focus on how the specificity of signal transmission by MAPKs is achieved by
      scaffolding molecules and by the presence of structural motifs in MAPKs that are
      dynamically regulated by phosphorylation and protein-protein interactions. We
      discuss also how MAPKs recognize and phosphorylate their target nuclear proteins,
      including transcription factors, co-activators and repressors and chromatin
      remodeling molecules, thereby affecting an intricate balance of nuclear
      regulatory molecules that ultimately control gene expression in response to
      environmental cues.

PMID- 17496920
TI  - Systems biology analysis of G protein and MAP kinase signaling in yeast.
AB  - Approximately a third of all drugs act by binding directly to cell surface
      receptors coupled to G proteins. Other drugs act indirectly on these same
      pathways, for example, by inhibiting neurotransmitter reuptake or by blocking the
      inactivation of intracellular second messengers. These drugs have revolutionized
      the treatment of human disease. However, the complexity of G protein signaling
      mechanisms has significantly hampered our ability to identify additional new drug
      targets. Moreover, today's molecular pharmacologists are accustomed to working on
      narrowly focused problems centered on a single protein or enzymatic process. Here
      we describe emerging efforts in yeast aimed at identifying proteins and processes
      that modulate the function of receptors, G proteins and MAP kinase effectors. The
      scope of these efforts is far more systematic, comprehensive and quantitative
      than anything attempted previously, and includes integrated approaches in
      genetics, proteomics and computational biology.

PMID- 17496921
TI  - Wiring the cell signaling circuitry by the NF-kappa B and JNK1 crosstalk and its
      applications in human diseases.
AB  - Integration of the cell signaling circuitry determines the ultimate response of a
      cell to extracellular stimuli. The transcription factor nuclear factor-kappa B
      (NF-kappaB) and mitogen-activated protein kinase JNK1 are major players in the
      cell signaling circuitry, regulating numerous cellular events and being
      implicated in the process of many human diseases and certain types of cancer. The
      interplay between NF-kappaB and JNK1 provides a paradigm that shows how the
      crosstalk between different signaling pathways decides the function of the cell
      signaling circuitry. Understanding the wiring of the cell signaling circuitry may
      hold the key for cell signaling-based therapy of human diseases.

PMID- 17496922
TI  - MAP kinase signalling pathways in cancer.
AB  - Cancer can be perceived as a disease of communication between and within cells.
      The aberrations are pleiotropic, but mitogen-activated protein kinase (MAPK)
      pathways feature prominently. Here, we discuss recent findings and hypotheses on
      the role of MAPK pathways in cancer. Cancerous mutations in MAPK pathways are
      frequently mostly affecting Ras and B-Raf in the extracellular signal-regulated
      kinase pathway. Stress-activated pathways, such as Jun N-terminal kinase and p38,
      largely seem to counteract malignant transformation. The balance and integration
      between these signals may widely vary in different tumours, but are important for
      the outcome and the sensitivity to drug therapy.

PMID- 17496923
TI  - Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the
      treatment of cancer.
AB  - Mitogen-activated protein kinase (MAPK) cascades are key signaling pathways
      involved in the regulation of normal cell proliferation, survival and
      differentiation. Aberrant regulation of MAPK cascades contribute to cancer and
      other human diseases. In particular, the extracellular signal-regulated kinase
      (ERK) MAPK pathway has been the subject of intense research scrutiny leading to
      the development of pharmacologic inhibitors for the treatment of cancer. ERK is a
      downstream component of an evolutionarily conserved signaling module that is
      activated by the Raf serine/threonine kinases. Raf activates the MAPK/ERK kinase
      (MEK)1/2 dual-specificity protein kinases, which then activate ERK1/2. The
      mutational activation of Raf in human cancers supports the important role of this
      pathway in human oncogenesis. Additionally, the Raf-MEK-ERK pathway is a key
      downstream effector of the Ras small GTPase, the most frequently mutated oncogene
      in human cancers. Finally, Ras is a key downstream effector of the epidermal
      growth factor receptor (EGFR), which is mutationally activated and/or
      overexpressed in a wide variety of human cancers. ERK activation also promotes
      upregulated expression of EGFR ligands, promoting an autocrine growth loop
      critical for tumor growth. Thus, the EGFR-Ras-Raf-MEK-ERK signaling network has
      been the subject of intense research and pharmaceutical scrutiny to identify
      novel target-based approaches for cancer treatment. In this review, we summarize
      the current status of the different approaches and targets that are under
      evaluation and development for the therapeutic intervention of this key signaling
      pathway in human disease.

PMID- 17496925
TI  - A role of estrogen/ERalpha signaling in BRCA1-associated tissue-specific tumor
      formation.
AB  - Estrogen and its receptor alpha (ERalpha) have been implicated in the tissue
      specific tumorigenesis associated with BRCA1 mutations. However, the majority of
      breast cancers developed in human BRCA1 mutation carriers are ERalpha-negative,
      challenging the link between BRCA1 and estrogen/ERalpha in breast cancer
      formation. Using a mouse model lacking the full-length form of BRCA1, here we
      show that ERalpha is highly expressed in the premalignant mammary gland and
      initiation stages of tumorigenesis, although its expression is gradually
      diminished during mammary tumor progression. We demonstrate that the absence of
      full-length BRCA1 increases sensitivity of cells to estrogen-induced
      extracellular signal-regulated kinase 1/2 phosphorylation and cyclin D1
      expression. The absence of BRCA1 turns the proliferation of ERalpha-positive
      cells from a paracrine fashion to an autocrine or endocrine fashion.
      Consequently, BRCA1-mutant cells are sensitized to estrogen-induced cell
      proliferation in vitro and mammary tumorigenesis in vivo. These findings
      illustrate a molecular mechanism for estrogen/ERalpha signals in BRCA1-associated
      tissue-specific tumor formation, and identify several key elements in the
      estrogen/ERalpha-signaling cascade that can serve as potential therapeutic
      targets for BRCA1-associated tumorigenesis.

PMID- 17496924
TI  - Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1
      pathway.
AB  - Endoglin is a transforming growth factor beta (TGFbeta) superfamily auxiliary
      receptor. We had previously shown that it suppressed prostate cancer (PCa) cell
      motility, and that its expression was lost during PCa progression. The mechanism
      by which endoglin inhibits PCa cell motility is unknown. Here we demonstrate that
      endoglin abrogates TGFbeta-mediated cell motility, but does not alter cell
      surface binding of TGFbeta. By measuring Smad-specific phosphorylation and Smad
      responsive promoter activity, endoglin was shown to constitutively activate
      Smad1, with little-to-no effect upon Smad3. Knockdown of Smad1 increased motility
      and abrogated endoglin's effects. As type I activin receptor-like kinases (ALKs)
      are necessary for Smad activation, we went on to show that knockdown of ALK2, but
      not TGFbetaRI (ALK5), abrogated endoglin-mediated decreases in cell motility and
      constitutively active ALK2 was sufficient to restore a low-motility phenotype in
      endoglin deficient cells. These findings provide the first evidence that endoglin
      decreases PCa cell motility through activation of the ALK2-Smad1 pathway.

PMID- 17496926
TI  - Glucocorticoid receptor overexpression exerts an antisurvival effect on human
      small cell lung cancer cells.
AB  - Small cell lung cancer (SCLC) is an aggressive tumour with an abysmal prognosis.
      These cancers are characteristically resistant to glucocorticoid (Gc) action,
      owing to impaired expression of the glucocorticoid receptor (GR). We identified
      reduced GR expression in human SCLC cell lines, compared to a non-SCLC cell line.
      The SCLC cells also showed no Gc inhibition of proliferation, in contrast to non
      SCLC cells. Retroviral overexpression of GR resulted in significantly increased
      cell death, which was partially blocked by the GR antagonist, RU486. Indeed, in
      cells sorted for GR expression, there was rapid, near complete loss of live cells
      by 72 h, in contrast to control cells that proliferated as expected. Flow
      cytometry using Annexin V revealed that cell death was by apoptosis. In addition,
      confocal analysis of fixed cells showed that cells overexpressing GR displayed a
      significant increase in fragmenting apoptotic nuclei. Microarray studies showed
      that transgenic GR expression upregulated the proapoptotic genes, BAD and BAX. We
      have, therefore, identified a profound apoptotic effect of GR in SCLC cells,
      which may explain the low levels of endogenous GR in SCLC cells. Understanding
      how GR overexpression leads to apoptotic cell death in SCLC cells may uncover new
      therapeutic strategies.

PMID- 17496927
TI  - Expression profiling of Ral-depleted bladder cancer cells identifies RREB-1 as a
      novel transcriptional Ral effector.
AB  - Although the monomeric GTPases RalA and RalB have been shown to regulate a
      variety of transcription factors, little is known regarding the differences or
      similarities in transcriptional programs regulated by RalA compared to RalB.
      Further, the association of these transcriptional pathways to human
      carcinogenesis and progression remains unclear. Here, we studied the role of RalA
      and/or RalB in transcriptional regulation by combining short interfering RNA
      depletion of Ral with gene expression profiling via microarray in the human
      bladder cancer cell line, UMUC-3. A large number of genes were found to be
      similarly modulated in cells with RalA and RalB depletion, suggesting that RalA
      and RalB impinge on overlapping transcriptional signaling pathways. However,
      smaller sets of genes were modulated by depletion of RalA or RalB, indicating
      that these closely related proteins also regulate nonoverlapping transcriptional
      pathways. Computational analysis of upstream sequences of genes modulated by Ral
      depletion identified Ras-responsive element-binding protein (RREB)-1, as a
      putative Ral transcriptional target, which we verified experimentally.
      Importantly, as a group, Ral-regulated probe sets identified here were
      disproportionally represented among those differentially expressed as a function
      of human bladder transformation. Taken together, these data strongly suggest that
      Ral family members mediate both common and specific transcriptional programs that
      are associated with human cancer and identify RREB-1 as a novel transcriptional
      effector of Ral.

PMID- 17496928
TI  - Homeostatic chemokines increase survival of B-chronic lymphocytic leukemia cells
      through inactivation of transcription factor FOXO3a.
AB  - B-chronic lymphocytic leukemia (B-CLL) cell is characterized by the accumulation
      of long-lived CD5+ B lymphocytes, whose survival in vivo is in part dependent on
      exogenous factors such as cytokines and/or extracellular matrix proteins.
      Homeostatic chemokines are critical mediators of lymphoid cell trafficking.
      However, how they function in cell signaling and survival remains ill-defined. In
      this study, we have investigated the role of the homeostatic chemokines, CXCL12,
      CCL21, CCL19 and CXCL13, in B-CLL cell survival. Using primary leukemic cells
      isolated from 26 patients, we observed that each chemokine enhances cell
      survival. Chemokines induced the phosphorylation of ERK1/2 and p90RSK, and of Akt
      and its effectors GSK3 and FOXO3a. Consistently, inhibitors against mitogen
      activated protein kinase/extracellular signal-regulated kinase and
      phosphatidylinositol 3-kinase inhibited chemokine-induced survival. Moreover,
      using a constitutively active mutated form of FOXO3a or siRNAs against FOXO3a in
      transfection experiments performed in primary B-CLL cells, we directly
      demonstrated the critical role of FOXO3a in both spontaneous and chemokine
      induced B-CLL cell survival. Overall, our data support the notion that
      homeostatic chemokines contribute to B-CLL resistance to cell death through
      inactivation of the transcription factor FOXO3a, which may represent a novel
      therapeutic target in this hematopoietic malignancy.

PMID- 17496929
TI  - Eighth international mesothelioma interest group.
AB  - The eighth International Mesothelioma Interest Group (IMIG) meeting was held in
      Chicago, IL, United States, in 19-22 October 2006 to discuss mesothelioma - the
      cancer often linked to asbestos exposure. It is a very aggressive malignancy with
      a median survival of less than 1 year from diagnosis. Millions of people have
      been exposed worldwide to asbestos, especially during the second half of the
      twentieth century when asbestos use increased significantly. The tons of asbestos
      utilized in the past remain a health hazard for current and future generations
      because asbestos is difficult to be disposed off. This makes asbestos and
      mesothelioma research a public health issue in addition to a medical problem.
      Moreover, the very high costs of asbestos litigation have a significant impact on
      the whole economy. In the United States, up until 2001, defendant companies had
      paid 54 billion dollars in claims and estimated future liabilities ranged from
      145 to 210 billion. Therefore, asbestos research is of great interest to a large
      audience that includes patients, millions of asbestos-exposed individuals,
      scientists, physicians, public health officials, politicians, unions of asbestos
      workers, lawyers and the public at large. During the past few years, there has
      been significant progress in understanding the process of mineral fiber
      carcinogenesis and mesothelioma pathogenesis. With improved understanding of the
      pathogenesis of mesothelioma, new diagnostic, preventive and therapeutic options
      are being developed. A total of 247 papers were presented at the IMIG: the
      abstracts of these presentations were published in Lung Cancer, Supplement 1,
      October 2006. Here, experts in different disciplines critically review some of
      the most exciting presentations of the IMIG meeting. The result is a
      comprehensive review of the research field of asbestos carcinogenesis and
      mesothelioma, and of the progress that has been made in recent years in both
      basic and clinical sciences.

PMID- 17496930
TI  - Structure-function analysis of the interaction between Bax and the
      cytomegalovirus-encoded protein vMIA.
AB  - The viral mitochondrial inhibitor of apoptosis (vMIA) encoded by the human
      cytomegalovirus exerts cytopathic effects and neutralizes the proapoptotic
      endogenous Bcl-2 family member Bax by recruiting it to mitochondria, inducing its
      oligomerization and membrane insertion. Using a combination of computational
      modeling and mutational analyses, we addressed the structure-function
      relationship of the molecular interaction between the protein Bax and the viral
      antiapoptotic protein vMIA. We propose a model in which vMIA exhibits an overall
      fold similar to Bcl-X(L). In contrast to Bcl-X(L), however, this predicted
      conformation of vMIA does not bind to the BH3 domain of Bax and rather engages in
      electrostatic interactions that involve a stretch of amino acids between the BH3
      and BH2 domains of Bax and an alpha-helical domain located within the previously
      defined Bax-binding domain of vMIA, between the putative BH1-like and BH2-like
      domains. According to this model, vMIA is likely to bind Bax preferentially in
      its membrane-inserted conformation. The capacity of vMIA to cause fragmentation
      of the mitochondrial network and disorganization of the actin cytoskeleton is
      independent of its Bax-binding function. We found that Delta131-147 vMIA mutant,
      which lacks both the Bax-binding function and cell-death suppression but has
      intact mitochondria-targeting capacity, is similar to vMIA in its ability to
      disrupt the mitochondrial network and to disorganize the actin cytoskeleton.
      vMIADelta131-147 is a dominant-negative inhibitor of the antiapoptotic function
      of wild-type vMIA. Our experiments with vMIADelta131-147 suggest that vMIA forms
      homo-oligomers, which may engage in cooperative and/or multivalent interactions
      with Bax, leading to its functional neutralization.

PMID- 17496931
TI  - UVC inhibits HIF-1alpha protein translation by a DNA damage- and topoisomerase I
      independent pathway.
AB  - Hypoxia inducible factor 1 (HIF-1) is a key player in cancer progression and an
      attractive target for cancer therapy. Several small molecule inhibitors of HIF
      1alpha also induce a DNA damage response. However, whether or not DNA damage is
      required for or associated with the inhibition of HIF-1alpha protein accumulation
      is poorly understood. In this report we investigated the effects of distinct DNA
      damaging conditions on the hypoxic induction of HIF-1alpha protein in cancer cell
      lines. We demonstrate that in addition to topotecan (TPT), a known inhibitor of
      HIF-1alpha, UVC, but not other DNA damaging agents (cisplatin, ionizing radiation
      and doxorubicin), inhibited HIF-1alpha protein accumulation in a dose-dependent,
      p53-independent fashion. Low doses UVC decreased HIF-1alpha translation without
      affecting global protein synthesis. Inhibition of HIF-1alpha by UVC required
      ongoing RNA transcription, but not DNA replication. Moreover, a functional ATR
      was required for the activation of DNA damage-dependent responses by both UVC and
      TPT, but was dispensable for the inhibition of HIF-1alpha protein. Notably,
      unlike TPT, inhibition of HIF-1alpha protein by UVC did not require topoisomerase
      I, suggesting a similar yet distinct mode of action. Our data reveal that UVC is
      a novel signal associated with inhibition of HIF-1alpha protein accumulation, and
      they uncouple the DNA damage-dependent signaling pathway exerted by UVC and TPT
      from HIF-1alpha inhibition.

PMID- 17496932
TI  - ACTuDB, a new database for the integrated analysis of array-CGH and clinical data
      for tumors.
AB  - In recent years, an increasing number of projects have investigated tumor genome
      structure, using microarray-based techniques like array comparative genomic
      hybridization (array-CGH) or single nucleotide polymorphism (SNP) arrays. The
      forthcoming studies have to integrate these former results and compare their
      findings to the existing sets of copy number data for validation. These sets also
      form the basis from which many comparative retrospective analyses can be carried
      out. Nevertheless, exploitation of this mass of data relies on a homogeneous
      preparation of copy number data, which will make it possible to compare them
      together, and their integration into a unified bioinformatics environment with ad
      hoc analysis tools and interfaces. To our knowledge, no such data integration has
      been proposed yet. Therefore the biologists and clinicians involved in cancer
      research urgently need such an integrative tool, which motivated us to undertake
      the construction of a database for array-CGH and other DNA copy number data for
      tumors (ACTuDB). When available, the associated clinical, transcriptome and loss
      of heterozygosity data were also integrated into ACTuDB. ACTuDB contains
      currently about 1500 genomic profiles for tumors and cell lines for the bladder,
      brain, breast, colon, liver, lymphoma, neuroblastoma, mouth and pancreas,
      together with data for replication timing experiments. The CGH array data were
      processed, using ad hoc algorithms (probe mapping, breakpoint detection, gain or
      loss status assignment and visualization) developed at Institut Curie. The
      database is available from http://bioinfo.curie.fr/actudb/ and can be browsed
      with a user-friendly interface. This database will be a useful resource for the
      genomic profiling of tumors, a field of highly active research. We invite
      research groups involved in tumor genome profiling to submit their data to
      ACTuDB.

PMID- 17496933
TI  - The prognostic impact of some cell cycle regulatory proteins in Egyptian breast
      cancer patients.
AB  - PURPOSE: The particular goal of this work is to study some cell cycle regulatory
      proteins and their potential impact on prognosis of breast cancer; p53, cyclin D1
      and p27 are potential effectors being the major contributors to the control of
      the restriction (R) check point of the cell cycle. We also aimed to evaluate
      different techniques used to detect these cell cycle proteins. MATERIAL AND
      METHODS: Forty five breast cancer patients as well as 10 controls with non
      malignant pathology were assessed for cell cycle regulators each by 2 different
      techniques; p53 was assessed by enzyme immunoassay (EIA) and immunohistochemistry
      (IHC), cyclin D1 by Western Blotting (WB) and IHC and p27 by WB and IHC. The cut
      off was calculated as the mean of the normal controls +2 SD. Patients were
      followed up for 4 years and their laboratory data were correlated with different
      clinical parameters and with other studied regulators. RESULTS: Eighty seven
      percent of cases (39/45) were positive for p53 by EIA with a range from 20 to
      4300, and a mean of 464 +/- 971 pg/mg protein. By IHC, 80% (24/30) of the cases
      showed varying degrees of positivity. Using WB, cyclin D1 showed high expression
      levels above cut off values in 69% of patients (31/45) and in 67% (20/30) by IHC.
      The corresponding positive figures for p27 were 82% (37/45) and 73% (22/30) using
      the two techniques, respectively. No significant association was found between
      p53, cyclin D1 and p27 on one side and different clinical parameters as lymph
      node status, tumor size or presence of distant metastases on the other side.
      Survival was poor in patients with high p53 expression. Cyclin D1 positive cases
      showed comparable survival with negative cases, whereas high p27 levels favored a
      longer disease free survival. CONCLUSIONS: Techniques more suitable for
      assessment of each of these markers in our consideration were EIA for p53, WB for
      cyclin D1 and IHC for p27. Moreover, this study demonstrated that these markers
      were relevant to the biological behavior of the tumor cell per se with a possible
      impact on prognosis and survival, independent of other clinical prognostic
      factors.

PMID- 17496934
TI  - Histopathological assessment and immunohistochemical study of nasopharyngeal low
      grade MALT lymphoma.
AB  - INTRODUCTION: MALT lymphoma arises in a variety of body tissues, but most often
      in the stomach. Though relatively rare, these MALT lymphomas may arise within
      several sites in the head and neck, and often present diagnostic and therapeutic
      challenges. Immunohistochemical analysis are helpful in confirming the diagnosis
      between the MALT-lymphoma and the reactive lymphoid hyperplasia. MALT-type
      lymphoma demonstrated characteristic negative staining for CD3, CD5 and CD43,
      positive staining for CD20, and monotypic staining for either kappa or lambda
      light chain immunoglobulin markers, whereas reactive lymphoid hyperplasia all
      expressed B and T cell markers. MATERIAL AND METHODS: 41 Cases of nasopharyngeal
      masses were obtained from the files at pathology department, Mansoura Faculty of
      Medicine through the period from 2002 till 2006. 31 cases were corresponded
      histomorphologically to low-grade B-cell lymphoma of mucosa-associated lymphoid
      tissue (MALT) type and 10 patients with reactive lymphoid hyperplasia of the
      adenoid. Hematoxylin- eosin-stained slides were reviewed to confirm the
      diagnosis. Immunohistochemical studies were performed on formalin-fixed, paraffin
      embedded sections using the labeled streptavidin-biotin-peroxidase complex method
      with DAB as chromogen. The following antibodies were evaluated CD20, CD3, Kappa,
      lambda and cytokeratin antibodies. RESULTS: All cases of low grade MALT lymphoma
      show lymphoepithelial lesion and proliferation of centrocyte like cells. 14 cases
      (45.1%) show subepithelial plasma cells. Dutcher bodies were demonstrated in 10
      cases (32.2%). Monocytoid B-cells were seen in 12 cases (38.7%). Six (60%) out of
      the ten cases of adenoids show transmigrating lymphocyte without formation of
      lymphoepithelial lesion. All cases with MALT-type lymphoma expressed CD20 and not
      CD3 whereas 10 cases of adenoid, all expressed B and T cell markers.
      Immunohistochemical staining showed that 31 cases of low grade MALT lymphoma were
      positive for immunoglobin light chain (kappa or lambda) while 10 cases of adenoid
      were positive for both kappa and lambda light chain. CONCLUSION:
      Immunohistochemical analysis are helpful in confirming the diagnosis between the
      MALT-lymphoma and the reactive lymphoid hyperplasia of the nasopharynx.

PMID- 17496935
TI  - Molecular detection of BCR/ABL fusion gene in Saudi acute lymphoblastic leukemia
      patients.
AB  - BACKGROUND: Molecular cytogenetics is becoming one of the most useful tools
      targeting some genes which are generally considered to lead to leukemic
      transformation (as well as for numerical abnormalities). A fraction of acute
      lymphoblastic leukemia (ALL) cases carry the translocation t(9;22) (q34;q11.2)
      which juxtaposes the ABL proto-oncogene to the BCR gene generating a chimeric
      gene, BCR/ABL. This aberration is more frequent in adult ALL (20%-40%) than in
      pediatric ALL (<5%), and predicts poor clinical outcome. AIM OF OUR WORK: Is to
      study BCR/ABL fusion gene in ALL cases using fluorescent in situ hybridization.
      PATIENTS AND METHODS: Twenty newly diagnosed ALL patients, 16 adult and 4
      paediatric cases, were included in the study, 11 cases (55%) were of precursor B
      phenotype, 8 cases (40%) belonged to T lineage, while one case was biphenotypic
      expressing mainly precursor B cell markers tether with CD13, CD33, CD117,
      Detection of BCR/ABL fusion gene was done using interphase FISH technique and was
      confirmed molecularly using the RT-PCR technique. RESULTS: BCR/ABL fusion gene
      was negative in all the examined cases, yet abnormality involving 9q34, ABL gene,
      either by addition or deletion was detected in three cases (15%). Two of these
      cases were associated with BCR gene extra copies (three and four copies,
      respectively). CONCLUSION: This may reflect the frequency of association of ABL
      gene and BCR gene abnormality in our cases, and that absence of fusion gene
      BCR/ABL does not exclude their role in the leukomogenic process, yet a larger
      study is required to confirm and detect the prevalence of these gene disturbances
      in ALL and their association.

PMID- 17496936
TI  - Role of human papilloma virus (HPV) in common and genital warts and its relation
      to P53 expression.
AB  - BACKGROUND:  BACKGROUND AND AIM: Human papilloma viruses (HPVs) are small DNA
      tumor viruses that infect epithelial tissues and cause warts. One of the viral
      genes responsible for HPV's oncogenic activity is E6 which is known to inactivate
      the cellular p53 tumor suppressor gene. We aim to detect the presence of HPV
      infection and its different types in human warts, and to identify the relation
      between HPV and p53 expression in skin and genital lesions. PATIENTS AND METHODS:
      We studied markers of HPV infection in overall of 30 patients (20 with common
      warts, and 10 with genital warts). Also, 30 normal skin samples were taken from
      each patient as a normal control. Detection of HPV was done using polymerase
      chain reaction (PCR), and HPV typing was performed using LiPA (Line immuno Probe
      Assay). In addition, all skin lesions were examined by immunohistochemistry for
      p53 expression. RESULTS: In patients with common warts, HPV DNA was found in 4/20
      (20%) of cases which was of HPV types 11, 31, 6, 33 (p=0.28). Also, P53
      expression was found in 4/20 (20%) of cases (p=0.26). No single patient showed
      reactivity of both HPV and p53 expression. In patients with genital warts,
      however, HPV DNA was found in 6/10 (60%) of cases. Of these, 5 cases were
      positive for HPV type 6 and one case had HPV type 11. Three patients (30%) were
      positive for p53, and two of them (66%) were positive for both HPV and p53. In
      the normal skin control, 2/30 (6.6%) were positive for HPV DNA which were of
      types 5, and 31. CONCLUSIONS: We conclude that; (1) Prevalence rate of HPV
      infection in warts is higher than those of normal control group, and Egyptian
      patients with genital warts had higher prevalence rate of HPV than those with
      common warts, (2) In Egypt, HPV types 6, and 11 are the most prevalent genotypes
      associated with genital warts and HPV types 6, 11, 31, and 33 are associated with
      common warts, (3) There was no definite relation between p53 expression and HPV
      detection, (4) Also, there was no association between the different HPV types and
      p53 detection in these non-cancerous lesions.

PMID- 17496937
TI  - Predictive factors of local recurrence and survival following primary surgical
      treatment of phyllodes tumors of the breast.
AB  - BACKGROUND AND PURPOSE: The phyllodes tumor is characterized by its tendency to
      recur locally and occasionally to metastasize. Local recurrence and death from
      metastases are occasional, but consistent, theme in reports of patients with
      phyllodes tumors (PTs). The aim of this study was to determine parameters that
      influence outcome in this uncommon neoplasm. PATIENTS AND METHODS: Data from 79
      patients with phyllodes tumors were reviewed retrospectively, reclassifying the
      pathological material using the World Health Organization (WHO) criteria.
      RESULTS: The median age of the patients was 42 years with a range from 16 to 70
      years. The tumor size ranged from 2.5 to 24 cm, with a median of 11 cm. Based on
      the criteria proposed by WHO, 31 cases were benign tumors (39.2%), 27 borderline
      tumors (34.2%), and 21 malignant tumors (26.6%). The median duration of follow up
      was 60 months ranging from 3 to 138 months. Following local excision, the local
      recurrence rates were 14.3%, 50%, and 75% in patients with benign, borderline,
      and malignant tumors; respectively, while after wide local excision the local
      recurrence rates were 0%, 36.3% and 40%; respectively. Whereas, 0%, 8.3%, and
      8.3% of patients with benign, borderline and malignant tumors; respectively,
      locally recurred after mastectomy. The 5-year disease free survival was 63.3%
      after local excision, 70% after wide local excision, and was 87% after mastectomy
      (p=0.04). Distant metastases (DM) were recorded in 10 patients (12.6%) after a
      median duration of 14 months (range 3- 36). All cases with DM died after an
      average of 5 months with a range of 1 to 11 months. Distant metastases developed
      in 3.2%, 11.1%, and in 28.6% of patients with benign, borderline and malignant
      tumors; respectively. The 5-year survival with no evidence of disease was 90% for
      the patients with benign tumors compared to 69% for borderline and 61% for
      malignant PTs (p= 0.02). CONCLUSIONS: The histotype of phyllodes tumors and
      resection margins were the principal determinants of local recurrence and distant
      metastases. Complete surgical excision by either wide local excision or
      mastectomy if necessary is important in the primary surgical treatment of
      phyllodes tumors.

PMID- 17496938
TI  - Immediate breast reconstruction with expander assisted latissimus dorsi flap
      after skin sparing mastectomy.
AB  - BACKGROUND AND PURPOSE: The latissimus dorsi myocutaneous flap (LDMF) used to be
      the standard practice for breast reconstruction; however, with the increased use
      of tissue expanders and the development of the transverse rectus-abdominis
      myocutaneous flap for autologous tissue breast reconstruction, its use has
      decreased. To reassess the role of the LDMF in breast reconstruction, a
      prospective study was performed to evaluate women who had a skin sparing
      mastectomy followed by immediate reconstruction with a latissimus dorsi flap and
      tissue expander implant. PATIENTS AND METHODS: Twenty-five women with early
      breast cancer underwent immediate latissimus dorsi myocutaneous flaps with tissue
      expander after skin sparing mastectomy. The oncologic safety of skin sparing
      mastectomy, the postoperative aesthetic results and complications were evaluated.
      RESULTS: Between May 2003 and April 2005, 25 consecutive women diagnosed with
      breast cancer underwent skin sparing mastectomy and expander assisted immediate
      latissimus dorsi breast reconstruction. Their median age was 42 years, ranging
      from 34 to 48 years. The procedure duration ranged from 2.5 to 6 hours, with a
      median of 3.9 hours, however, expansion was completed by 4 months (range 1 to 8
      months). Patients were discharged 7 days after surgery with a range of 5 to 15
      days. The complication rate was low, manifesting with skin flap necrosis in 12%,
      wound infection in 4%, and port site extrusion in 4%. There was no flap loss.
      With the exception of seroma formation, the donor site morbidity was low (seroma
      40%, hematoma 4%, back pain 8%, and limited arm movement 4%). No local recurrence
      was recorded. The aesthetic result of surgery was rated as excellent in 20%, good
      in 60%, fair in 24%, and poor in 4% of cases. The duration of post-operative
      follow up was 14.7 months, ranging from 6 to 24 months. CONCLUSIONS: Skin sparing
      mastectomy and immediate breast reconstruction is an oncologically safe
      technique. The use of latissimus dorsi myocutaneous flap with tissue expansion
      has proved to be an effective and aesthetic method of immediate breast
      reconstruction after skin sparing mastectomy.

PMID- 17496939
TI  - Locally advanced cheek carcinoma; radical surgery and reconstruction of though
      and through defects.
AB  - BACKGROUND: Squamous cell carcinoma of the cheek is a locoregionally aggressive
      tumor. Radical resection may be curative in cases of large tumor without distant
      metastases. We reviewed forty eight consecutive cases of Sq.c.c. of the oral
      cavity to evaluate the feasibility and efficacy of the reconstructive method.
      PATIENTS AND METHODS: Forty eight cases of invasive Sq.c.c. affecting the cheek
      performed in Mansoura University, Surgical Oncology Department. From November
      2001 to October 2004 were included. Twenty cafes presented primarily, and 28 were
      relapsing after previous surgery or radiotherapy. Tumors of T3 and T4 size were
      included. Radical excision with adequate safety margin followed by reconstruction
      was done in the same setting using: A- Double layered pectoralis major flap
      (n=30). B- Pectoralis major flap for external surface and tongue flap for mucosal
      lining (n=10). C- Pectoralis major flap plus free Latissmus dorsi flap (n=3). D-
      Latissmus dorsi flap plus tongue flap (n=5). RESULTS: Nine cases (18.7%) had
      local and distant relapse after a median follow up period of 36 months. However,
      total flap loss was not encountered. There were partial loss of three tongue
      flaps, seven pectoralis flaps corrected with debridement and reapproximation. Two
      patients had oral incompetence. Orocutaneous salivary fistula persistent more
      than three weeks occurred in eight patients. Functional outcome in terms of oral
      competence, sensibility, chewing movements was satisfactory in all but three
      cases. IN CONCLUSION: Radical resection of extensive cheek carcinoma and
      reconstruction using pedicled flaps is an effective, economic and reliable method
      for oncologic and functional purposes.

PMID- 17496940
TI  - Treatment results of nasopharyngeal carcinoma: a 15-year single institutional
      experience.
AB  - BACKGROUND: Nasopharyngeal Carcinoma (NPC) is a common malignant neoplasm of the
      head and neck that occurs most commonly in people in the South Eastern Asia but
      its condition in Iran is not much clear. OBJECTIVE: In this retrospective study,
      we evaluated the treatment characteristics determining the outcome in patients
      with NPC. PATIENTS AND METHODS: In this retrospective study, we reviewed the
      records of one hundred and seven patients with biopsy proven diagnosis of NPC who
      were referred to the radiation oncology department, Nemazee Hospital, Shiraz
      University of Medical Sciences, Iran, during the time period from January 1985 to
      December 2000. Eightyfive patients (79.4%) received 60-70Gy radiation (1.8-
      2Gy/fraction, one fraction per day, and 5 fractions per week). Sixty-two patients
      (57.5%) received radiotherapy combined with adjuvant chemotherapy which consisted
      of cisplatin and 5-fluorouracil. Eighty-six patients (80.4%) had WHO II-III
      histopathologic diagnosis. According to the AJCC 1997 staging system, 4 (3.6%), 3
      (2.7%), 33 (30.8%) and 67 (62%) patients were in stages I, II, III and IV,
      respectively. RESULTS: With a median follow-up of 12 months, the 2-year overall
      and disease-free survival rates were 35% and 21%, respectively. According to the
      multivariate analysis for overall survival, patients under 40 years had a better
      prognosis (p=0.041). Node stage and stage of disease were significant prognostic
      factors (p=0.0001). On multivariate analysis for disease-free survival, age and
      node stage were significant prognostic factors. The patients who received more
      than 60Gy radiation had a better prognosis (p=0.02), however; sequential adjuvant
      chemotherapy had no impact on survival and response (p=0.6). CONCLUSION: Our
      experience confirmed earlier reports showing poor outcomes for locoregionally
      advanced nasopharyngeal carcinomas. This study failed to demonstrate improvement
      in the outcome regarding overall and disease-free survival by adding sequential
      adjuvant chemotherapy after radiotherapy for patients with advanced NPC.

PMID- 17496941
TI  - Sigmoid colon is an unexpected organ at risk in brachytherapy for cervix cancer.
AB  - PURPOSE: To identify organs at risk (OAR) and analyze the dose volume histograms
      (DVHs) for intracavitary brachytherapy in cancer of the cervix. Late toxicities
      are our concern in treatment of cancer cervix especially as it is presenting in
      younger age population. MATERIAL AND METHODS: Patients with cancer of the cervix
      were treated using CT and MRI compatible, high dose rate, (HDR) applicators. CT
      images were acquired with the intra-uterine tube and colpostats in place and
      subsequently imported into Varian Brachyvision planning software. We identified
      the gross tumour volume (GTV) and organs at risk (OARs) and analyzed the dose
      distribution using dose volume histograms (DVHs). Doses were calculated according
      to ICRU 38. Critical tissue DVHs were analysed following the American
      Brachytherapy Society rules. Dose points are recorded as the dose encompassed by
      the greatest contiguous 1 cm3, 2 cm3, and 5 cm3 volumes in the plan. RESULTS: We
      found the sigmoid colon to be a relatively immobile structure that repeatedly
      received doses in excess of 70% of the intended point A dose. The only solution
      in order to bring sigmoid DVHs within 5% toxicity limits was to reduce the dose
      to point A. Planning images and DVHs for the OARs are shown as an example of our
      work. CONCLUSION: The recto-sigmoid colon is identified as an unexpected OAR in a
      majority of cervix brachytherapy plans. A new consensus on the DVH limit of this
      structure will be needed in the era of CT planned brachytherapy, if arbitrary
      dose reductions to point A are to be the solution to the problem of sigmoid DVHs
      that exceed conventional tolerance limits.

PMID- 17496942
TI  - Spinal cord doses in palliative lung radiotherapy schedules.
AB  - AIM: We aim to check the safety of the standard palliative radiotherapy
      techniques by using the Linear quadratic model for a careful estimation of the
      doses received by the spinal cord, in all standard palliative lung radiotherapy
      fields and fractionation. MATERIAL AND METHODS: All patients surveyed at this
      prospective audit were treated with palliative chest radiotherapy for lung cancer
      over a period from January to June 2005 by different clinical oncology
      specialists within the department. Radiotherapy field criteria were recorded and
      compared with the recommended limits of the MRC trial protocols for the dose and
      fractionation prescribed. Doses delivered to structures off the field central
      axis were estimated using a standard CT scan of the chest. Dose estimates were
      made using an SLPLAN planning system. As unexpected spinal cord toxicity has been
      reported after hypofractionated chest radiotherapy, a sagittal view was used to
      calculate the isodoses along the length of the spinal cord that could lie within
      the RT field. Equivalent dose estimates are made using the Linear- Quadratic
      Equivalent Dose formula (LQED). The relative radiation sensitivity of spinal cord
      for myelopathy (the a/b dose) cord has been estimated as a/b = 1 Gy. RESULTS: 17
      Gy in 2 fraction and 39 Gy in 13 fraction protocols have spinal cord equivalent
      doses (using the linear-quadratic model) that lie within the conventional safe
      limits of 50 Gy in 25 fractions for the 100% isodose. However when the dosimetry
      is modelled for a 6 MV 100 cm isocentric linnac in 3 dimensions, and altered
      separations and air space inhomogeneity are considered, the D-Max doses
      consistently fall above this limit on our 3 model patients. CONCLUSION: The 17 Gy
      in 2 fraction and 39 Gy in 13 fraction protocol would risk spinal cord damage if
      the radiotherapist was unaware of the potential spinal cord doses. Alterative
      doses are suggested below 15.5 Gy/ 2 fractions (7 days apart) would be most
      acceptable.

PMID- 17496943
TI  - Concomitant weekly vincristine and radiation followed by adjuvant vincristine and
      carboplatin in the treatment of high risk medulloblastoma: Ain Shams University
      Hospital and Sohag Cancer Center study.
AB  - PURPOSE: To evaluate survival, progression free survival (PFS) and toxicity of
      children with newly diagnosed high risk medulloblastoma who were treated with
      weekly vincristine concurrently during irradiation followed by adjuvant
      carboplatin and vincristine. PATIENTS AND METHODS: High risk medulloblastoma
      patients with postoperative gross residual disease that was >1.5 cm2 and/or
      metastatic disease (M+) were planned to receive craniospinal irradiation (CSI) 36
      Gy followed by boost to the posterior fossa for a total of 55.8 Gy. Concomitantly
      during radiation, patients received weekly vincristine 1.5 mg/m2. Six weeks after
      completion of radiation therapy, patients were scheduled on a regimen of weekly
      vincristine (1.5 mg/m2) and carboplatin (150 mg/m2) for 4 weeks, 3 weeks rest
      then another cycle for a total of 48 weeks. RESULTS: The study included seventeen
      high risk medulloblastoma patients presented to Ain Shams University hospitals
      and Sohag Cancer Center between November 2001 and March 2005. Their median age
      was 8.4 years (range from 5 to 14 years), they were 12 males and 5 females. The
      overall survival at three year was 70.6% and the 3-year PFS was 58.8%. The 3-year
      overall survival for M+ patients was 50% Vs. 81.8% for M0 patients (p=0.04). The
      3-year PFS was 50% for M+ patients Vs. 63.6% for M0 patients (p=0.15). The
      treatment was well tolerated. During CSI, 3 patients only (17.6%) developed grade
      3 neutropenia. During adjuvant chemotherapy, the complications were more frequent
      and of deeper degree. Grade 3 and 4 neutropenia were observed in 5 patients
      (29%). One patient (6%) developed grade 3 peripheral neuropathy. CONCLUSION: Our
      results show that the present chemotherapy and radiotherapeutic approach is able
      to improve overall survival and PFS in high risk patients with gross residual
      disease but not in patients with metastatic disease (M+) that may require more
      intensive therapy.

PMID- 17496944
TI  - Microfungi associated with Abies needles and Betula leaf litter in a subalpine
      coniferous forest.
AB  - We investigated microfungal assemblages on leaf litter within a subalpine forest
      in central Japan and their variation with season, litter depth, and litter
      species. Microfungal assemblages were compared for Abies needles and Betula leaf
      litter collected from litter and fermentation layers of the forest floor during
      the growing season in spring, summer, and autumn. A total of 35 and 42 species
      were isolated from Abies needles and Betula leaf litter, respectively. The
      observed variation in microfungal assemblages was primarily attributable to
      seasonal differences. The frequencies of Trichoderma viride, Volutella ciliata,
      Mucor sp., and Umbelopsis ramanniana increased in summer, leading to a high
      degree of similarity of microfungal assemblages in different litter depths and
      litter species. Microfungal assemblages on Abies needles in spring and autumn and
      those on Betula leaves in spring were characterized by Trichoderma viride, V.
      ciliata, Thysanophora penicillioides, Trichoderma polysporum, and (or)
      Mortierella alpina. Microfungal assemblages on Betula leaves in autumn were
      characterized by the absence of these species and the occurrence of Cladosporium
      cladosporioides. The results were discussed with an emphasis on the role of
      microfungi in decomposition processes and the impact on fungi of predicted future
      increases in global temperature.

PMID- 17496945
TI  - Haloarchaeal communities in the crystallizers of two adriatic solar salterns.
AB  - Solar salterns operate only for short dry periods of the year in the north shore
      of the Adriatic Sea because of its relatively humid and cold Mediterranean
      climate. In a previous paper, we showed that the NaCl precipitation ponds
      (crystallizers) of Northern Adriatic Secovlje salterns have different
      haloarchaeal populations from those typically found in dry and hot climates such
      as Southern Spain. To check whether there is a common pattern of haloarchaeal
      diversity in these less extreme conditions, diversity in crystallizers of other
      Adriatic solar salterns in Ston, Croatia was ascertained by molecular and culture
      methods. In addition, the cultivation approach was used to further describe
      haloarchaeal diversity in both salterns. Over the period of two solar salt
      collection seasons, isolates related to species of the genera Haloferax,
      Haloarcula, and Haloterrigena were recovered from both salterns. Within the same
      sampling effort, relatives of the genus Halorubrum and a Natrinema-like isolate
      were cultivated from Slovenian Secovlje salterns while Halobacterium related
      isolates were obtained from the Croatian Ston salterns. Concurrent with our
      previous findings, a library of Croatian saltern crystallizer PCR-amplified 16S
      rRNA genes was dominated by sequences related to the genus Halorubrum. The
      microbial community structure was similar in both salterns but diversity indices
      showed greater values in Slovenian salterns when compared with Croatian salterns.

PMID- 17496946
TI  - Comparison of enterotoxigenic Escherichia coli isolated from surface water and
      diarrhoeal stool samples in Bangladesh.
AB  - Enterotoxigenic Escherichia coli (ETEC) is a common cause of bacterial infection
      leading to acute watery diarrhea in infants and young children. Although the
      prevalence of ETEC is high in Bangladesh and infections can be spread through
      food and contaminated water, limited information is available about ETEC in the
      surface water. We carried out studies to isolate ETEC from surface water samples
      from ponds, rivers, and a lake from a site close to field areas known to have a
      high incidence of diarrhea in Dhaka, Bangladesh, and Matlab, Bangladesh. ETEC
      strains isolated from the water sources were compared with ETEC strains isolated
      from patients with diarrhea at two hospitals in these areas. ETEC were isolated
      from 30% (45 of 150) of the samples from the surface water sources and 19% (518
      of 2700) of the clinical specimens. One hundred ETEC strains isolated from
      patients with similar phenotypes as the environmental strains were compared for
      phenotypic and genotypic properties. The most common O serogroups on ETEC were
      O6, O25, O78, O115, and O126 in both types of strains. Pulsed-field gel
      electrophoresis analyses of the ETEC strains showed that multiple clones of ETEC
      were present within each colonization factor type and that some clones detected
      in the environment were also isolated from the stools of patients. The strains
      showed multiple and similar antibiotic resistance patterns. This study shows that
      ETEC is prevalent in surface water sources in Bangladesh suggesting a possible
      reason for the endemicity of this pathogen in Bangladesh.

PMID- 17496947
TI  - Phylogenetic relationships of Campylobacter jejuni based on porA sequences.
AB  - Campylobacter porins are the dominant major outer membrane protein (MOMP) of
      these bacteria. They are composed of hypervariable, surface-exposed, peptide
      loops and membrane-embedded, conserved peptide regions. Porins are functionally
      important and may also be useful for molecular subtyping methods but have not yet
      been well characterized. We therefore sequenced the porA gene from 39
      Campylobacter isolates, including multilocus sequence type (MLST) reference
      strains, isolates from patients with the Guillain-Barre syndrome, other clinical
      isolates, and serotyping reference strains. These were compared with additional
      sequences available from GenBank. Three distinct porA lineages were observed
      after phylogenetic analysis. Both Campylobacter coli and Campylobacter jejuni
      were found with group 3 porA sequences, and this was the only group showing any
      evidence of recombination among porA genes. There was no recombination between
      porA genes from C. jejuni groups 1 and 2, suggesting there may be functional
      constraints on changes at this locus. Most of the amino acid differences among
      the three groups were present in surface-exposed loops, and dissimilar
      substitutions were found when groups 1 and 2 MOMP were compared. Different MOMP
      sequence groups may have different biological or antigenic properties, which in
      turn may be associated with survival in different environments, host adaptation,
      or virulence.

PMID- 17496948
TI  - Sampling bias created by ampicillin in isolation media for Aeromonas.
AB  - Members of the bacterial genus Aeromonas are widely isolated from aquatic
      environments and studied in part for their ability to act as opportunistic
      pathogens in a variety of animals. All aeromonads, with the exception of
      Aeromonas trota, are generally thought to be resistant to ampicillin, so the
      antibiotic is frequently added to isolation medium as a selective agent. In this
      study, 282 aeromonads from environmental sources were isolated on a medium
      without ampicillin and their resistance to ampicillin determined. Of the 104 of
      these isolates that were judged to be independent (nonredundant), 18 (17.3%) were
      susceptible to ampicillin. A chi-square analysis was performed to determine the
      impact of ampicillin use on enumerating Aeromonas species from environmental
      samples. Our results indicate that, when ampicillin is used as a selective agent,
      a significant portion of the aeromonad population in at least some environments
      can be omitted from isolation.

PMID- 17496949
TI  - Agrichemical impact on growth and survival of non-target apple phyllosphere
      microorganisms.
AB  - The impact of conventional agrichemicals commonly used in New Zealand apple
      production on non-target, culturable phyllosphere microbial populations was
      studied in the laboratory (agar, leaf, and seedling assays) and field (apple
      orchard). Morphologically distinct bacteria (three), yeasts (five), and
      filamentous microfungi (two) were used as indicator species. The agar assay
      showed that agrichemical toxicity to microorganisms was dependent on product
      type, product rate, and organism studied. While the fungicides metiram and captan
      stopped or severely reduced growth of nearly all microorganisms studied, the
      insecticides tebufenozide and lufenuron and the fungicide nitrothal-isopropyl
      showed the least amount of microbial toxicity, each affecting 2 of the 10
      indicator organisms studied. In the leaf assay a single agrichemical application
      at field rate either reduced or increased microbial population counts, again
      depending on product and microorganism. Repeated agrichemical applications,
      however, reduced microbial population numbers from 10- to 10,000-fold in planta.
      Further field research validated these findings, although differences in
      microbial numbers before and after agrichemical applications were less dramatic.
      In the orchard, total organism numbers recovered within 2-6 days, but species
      richness (sum of recognizable taxonomic units) declined. Agrichemicals clearly
      affected non-target, culturable surface microorganisms. The importance of
      diversity and stability of microbial populations for disease control still needs
      to be established.

PMID- 17496950
TI  - An efficient system for markerless gene replacement applicable in a wide variety
      of enterobacterial species.
AB  - We describe an improved allelic-exchange method for generating unmarked mutations
      and chromosomal DNA alterations in enterobacterial species. Initially developed
      for use in Salmonella enterica, we have refined the method in terms of time,
      simplicity, and efficiency. We have extended its use into related bacterial
      species that are more recalcitrant to genetic manipulations, including
      enterohemorrhagic and enteropathogenic Escherichia coli and Vibrio
      parahaemolyticus. Data from over 50 experiments are presented including gene
      inactivations, site-directed mutagenesis, and promoter exchanges. In each case,
      desired mutations were identified by polymerase chain reaction screening
      typically from as few as 10-20 colonies up to a maximum of 300 colonies. The
      method does not require antibiotic nor nutritional markers in target genes and
      works efficiently in wild-type strains, obviating the need for specialized hosts
      or genetic systems. The use is simple, requiring basic laboratory materials, and
      represents an alternative to existing methods for gene manipulation in the
      Enterobacteriaceae.

PMID- 17496951
TI  - Characterization and control of endophytic bacterial contaminants in in vitro
      cultures of Piper spp., Taxus baccata subsp. wallichiana, and Withania somnifera.
AB  - Bacterial contamination is a serious problem that causes severe loss of in vitro
      grown cultures of a number of plants. This problem becomes even more acute if the
      bacterial contamination is of endophytic origin. In such cases, identification
      and characterization of the contaminants is essential for achieving specific
      control of the contaminants through selective use of antibiotic agents,
      especially if the routinely used contamination control methods practiced
      elsewhere in tissue culture studies are ineffective. Such is the case with the
      bacterial contamination observed in the present study. The five endophytic
      bacteria associated with Piper nigrum and Piper colubrinum, four endophytic
      bacteria associated with Taxus baccata subsp. wallichiana, two endophytic
      bacteria associated with Withania somnifera, and two bacteria common to all these
      plant species were isolated and characterized based on morphological and
      biochemical tests. Their taxonomic positions based on similarity indices were
      determined. A control strategy against these bacteria has been developed based on
      bacteriostatic or bactericidal actions of 12 antibiotics at three different
      concentrations by solid and liquid antibiogramme assays.

PMID- 17496952
TI  - Antibacterial activity of aerial parts as well as in vitro raised calli of the
      medicinal plant Saraca asoca (Roxb.) de Wilde.
AB  - Leaves, stem, and flowers of Saraca asoca, an endangered medicinal plant in
      India, and young explants cultivated on Murashige & Skoog's medium containing 6
      benzylaminopurine were analyzed for antibacterial potential. Alcoholic and
      aqueous extracts from parent explants and their in vitro raised calli were tested
      by an agar well diffusion method. Minimal inhibitory concentrations (MICs) of the
      extracts were determined by broth microdilution method. Aqueous extracts showed
      antibacterial activity against limited bacterial species, whereas alcoholic
      extracts were active against a wider range of bacteria. Although the alcoholic
      extracts of all the explants and calli showed antibacterial activity, the
      extracts derived from flowers and their calli showed better results. Extracts
      derived from calli showed comparable results to the extracts from explants.
      Overall, the MICs of the extracts ranged from 0.039 to 1.25 mg/mL. MICs against
      gram-positive bacteria ranged from 0.078 to 1.25 mg/mL, whereas they ranged
      between 0.039 and 0.625 mg/mL against gram-negative bacteria. A MIC distribution
      plot showed that gram-negative bacteria were more susceptible to the extracts
      than gram-positive bacteria. It is concluded that extracts of S. asoca contain
      antibacterial agent, and as the calli gave good results, in vitro cultivation of
      the explants may be used to obtain antibacterial compounds. This is the first
      report on antibacterial activity of S. asoca, especially through in vitro raised
      calli.

PMID- 17496953
TI  - SigmaB and SarA independently regulate polysaccharide intercellular adhesin
      production in Staphylococcus epidermidis.
AB  - The production of polysaccharide intercellular adhesin (PIA) is an essential
      process in foreign body infections mediated by Staphylococcus epidermidis.
      Transcriptional regulation of the icaADBC operon, the genes responsible for
      production of enzymes that synthesize PIA, is multi-factorial and involves at
      least SarA and sigmaB. Transcriptional and promoter fusion studies revealed that
      the decreased transcription of the icaADBC operon observed in a S. epidermidis
      1457 sigB mutant is not mediated through a direct interaction of sigmaB-RNA
      polymerase at the icaADBC promoter region but instead through the upregulation of
      IcaR, a known repressor of icaADBC transcription. Transcriptional analysis of a
      1457 sigB-icaR double mutant confirmed that the decreased icaADBC transcript in
      1457 sigB is IcaR dependent. Furthermore, primer extension studies suggest that
      the icaR promoter appears to be sigmaA dependent, suggesting that sigmaB
      indirectly controls icaR transcription through an unknown pathway. In addition,
      it was confirmed that the loss of SarA results in the loss of icaADBC
      transcription and PIA production in S. epidermidis. It was further demonstrated,
      through the over-production of SarA in 1457 sigB, that the loss of sarP1 promoter
      activity in 1457 sigB has little or no effect on the loss of PIA production in
      this mutant. Finally, it was demonstrated that PIA production could be restored
      in both 1457 sigB and 1457 sarA by complementing these mutants with a full-length
      icaADBC operon controlled by a cadmium-inducible noncognate promoter. It is
      concluded that sigmaB and SarA operate independently of each other to regulate
      PIA production and biofilm development in S. epidermidis.

PMID- 17496954
TI  - Identification of mycobacteria in peat moss processing plants: application of
      molecular biology approaches.
AB  - Peat moss processing plant workers are exposed to high concentrations of
      bioaerosols. Although mycobacteria have been cultured from peat moss, no study
      has examined the workers' exposure to mycobacterial bioaerosols. We evaluated the
      presence of mycobacteria in air samples from peat moss processing plants using
      molecular biology approaches (cloning-sequencing and polymerase chain reaction
      (PCR)) and the workers exposure using immunoglobulin G (IgG) complexes to
      mycobacteria. In addition, species detected in air samples and in peat moss were
      compared. Two peat moss processing plants were chosen among 14 previously
      studied. A total of 49 clones were sequenced. Real-time PCR was also performed on
      the same air samples to evaluate the airborne concentration of mycobacteria and
      estimate exposure levels. Several Mycobacterium species were present in the air
      samples (M. malmoense, M. smegmatis, M. graceum, M. bohemicum, and M.
      interjectum). Mycobacterium avium was recovered by culture in peat moss but not
      in the air using the molecular approach. Total airborne Mycobacterium
      concentration was estimated at 8.2 x 10(8)/m3. Workers had IgG against the
      mycobacterial mix and M. avium, suggesting significant exposure. The findings
      from air samples, supported by IgG measurements, demonstrate that peat moss
      processing plant workers are exposed to mycobacteria in addition to other
      biological agents.

PMID- 17496955
TI  - The glnAntrBC operon of Herbaspirillum seropedicae is transcribed by two
      oppositely regulated promoters upstream of glnA.
AB  - Herbaspirillum seropedicae is an endophytic bacterium that fixes nitrogen under
      microaerophilic conditions. The putative promoter sequences glnAp1 (sigma70
      dependent) and glnAp2 (sigma54), and two NtrC-binding sites were identified
      upstream from the glnA, ntrB and ntrC genes of this microorganism. To study their
      transcriptional regulation, we used lacZ fusions to the H. seropedicae glnA gene,
      and the glnA-ntrB and ntrB-ntrC intergenic regions. Expression of glnA was up
      regulated under low ammonium, but no transcription activity was detected from the
      intergenic regions under any condition tested, suggesting that glnA, ntrB and
      ntrC are co-transcribed from the promoters upstream of glnA. Ammonium regulation
      was lost in the ntrC mutant strain. A point mutation was introduced in the
      conserved -25/-24 dinucleotide (GG-->TT) of the putative sigma54-dependent
      promoter (glnAp2). Contrary to the wild-type promoter, glnA expression with the
      mutant glnAp2 promoter was repressed in the wild-type strain under low ammonium
      levels, but this repression was abolished in an ntrC background. Together our
      results indicate that the H. seropedicae glnAntrBC operon is regulated from two
      functional promoters upstream from glnA, which are oppositely regulated by the
      NtrC protein.

PMID- 17496956
TI  - The effect of Penicillium fungi on plant growth and phosphorus mobilization in
      neutral to alkaline soils from southern Australia.
AB  - The phosphate solubilizing fungi Penicillium radicum, Penicillium bilaiae (strain
      RS7B-SD1), and an unidentified Penicillium sp. designated strain KC6-W2 were
      tested for their ability to increase the growth and phosphorus (P) nutrition of
      wheat, medic, and lentil in three soils of neutral to alkaline pH reaction. The
      strongest plant growth promoting (PGP) strain was Penicillium sp. KC6-W2, which
      stimulated significant increases in shoot growth and dry mass in seven of the
      nine experiments conducted. Levels of PGP by Penicillium sp. KC6-W2 ranged from
      6.6% to 19% and were associated with increased uptake of P to the shoot. The PGP
      properties of Penicillium sp. KC6-W2 were evident on each of the three different
      plant species and soil types, a level of reliability not observed in other
      strains tested. Inoculation of seed with P. radicum increased lentil growth by
      5.5% (P < 0.05) in soil from Tarlee but did not affect plant growth in the eight
      other experiments. Inoculation of plant seed with P. bilaiae RS7B-SD1 resulted in
      significant PGP in two of the nine experiments conducted. However, when
      significant, stimulation of PGP by P. bilaiae RS7B-SD1 was strong and resulted in
      increases in medic dry matter (19%) and lentil shoot dry matter (15%). A soil
      microcosm experiment investigated the effect of Penicillium fungi on cycling of
      soil P. Penicillium bilaiae RS7B-SD1 was the only fungus to significantly
      increase HCO3-extractable P (23% increase; P < 0.05). Production of phosphatase
      enzymes was not associated with increased HCO3-extractable P. Addition of carbon
      in the form of ryegrass seed significantly increased microbial respiration and
      movement of P to the microbial biomass (P < 0.05), but these parameters were
      irrespective of Penicillium treatment. This work has established the potential
      for use of Penicillium inoculants to increase plant growth on alkaline soils in
      Australia. The role of Penicillium fungi in plant P uptake and soil P cycling
      requires further exploration.

PMID- 17496957
TI  - Heterogeneity between 16S ribosomal RNA gene copies borne by one
      Desulfitobacterium strain is caused by different 100-200 bp insertions in the 5'
      region.
AB  - Strains of Desulfitobacterium hafniense, such as strains PCP-1, DP7, TCE1, and
      TCP-A, have unusual long 16S ribosomal RNA (rRNA) genes due to an insertion of
      approximately 100 bp in the 5' region. In this report, we analyzed the 16S rRNA
      genes of different Desulfitobacterium strains to determine if such an insertion
      is a common feature of desulfitobacteria. We amplified this region by polymerase
      chain reaction (PCR) from eight Desulfitobacterium strains (D. hafniense strains
      PCP-1, DP7, TCP-A, TCE1, and DCB-2; D. dehalogenans; D. chlororespirans; and
      Desulfitobacterium sp. PCE1) and resolved each PCR product by denaturing gradient
      gel electrophoresis (DGGE). All strains had from two to seven DGGE- migrating
      bands, suggesting heterogeneity in their 16S rRNA gene copies. For each strain,
      the 5' region of the 16S rRNA genes was amplified and a clone library was
      derived. Clones corresponding to most PCR-DGGE migration bands were isolated.
      Sequencing of representative clones revealed that the heterogeneity was generated
      by insertions of 100-200 bp. An insertion was found in at least one copy of the
      16S rRNA gene in all examined strains. In total, we found eight different types
      of insertions (INS1-INS8) that varied from 123 to 193 nt in length. Two
      dimensional structural analyses of transcribed sequences predicted that all
      insertions would form an energetically stable loop. Reverse transcriptase-PCR
      experiments revealed that most of the observed insertions in the
      Desulfitobacterium strains were excised from the mature 16S rRNA transcripts.
      Insertions were not commonly found in bacterial 16S rRNA genes, and having a
      different insertion in several 16S rRNA gene copies borne by a single bacterial
      species was rarely observed. The function of these insertions is not known, but
      their occurrence can have an important impact in deriving 16S rRNA
      oligonucleotidic fluorescence in situ hybridization probes, as these insertions
      can be excised from 16S rRNA transcripts.

PMID- 17496958
TI  - Novel soil lineages of Archaea are present in semi-arid soils of eastern
      Australia.
AB  - The diversity of Archaea was studied in vertisolic and loam soils of a semi-arid
      region in Australia. Sampling was undertaken at an agricultural site, two
      grassland environments, and a brigalow (Acacia harpophylla) woodland. Archaeal
      community structure was profiled using amplified ribosomal DNA restriction
      analysis (ARDRA) combined with rDNA sequencing of an example of each restriction
      fragment length polymorphism type. Sequence comparison and phylogenetic analysis
      demonstrated that both crenarchaeotal and euryarchaeotal Archaea were present at
      oxic depths in the soil at all field sites. Along with previously described soil
      archaeal lineages, novel soil lineages and the deeply divergent Pendant-33 group
      of Euryarchaeota were also detected. A novel statistical method for comparing
      ARDRA derived data was demonstrated and implemented using the archaeal
      communities from the four field sites. Archaeal diversity, as measured by this
      method, was significantly higher in the agricultural site than at either of the
      grassland sites or the brigalow woodland.

PMID- 17496959
TI  - Effect of the addition of nitrogen sources to cassava fiber and carbon-to
      nitrogen ratios on Agaricus brasiliensis growth.
AB  - The same substratum formulation to grow Agaricus bisporus has been used to grow
      Agaricus brasiliensis since its culture started in Brazil. Despite being
      different species, many of the same rules have been used for composting or axenic
      cultivation when it comes to nitrogen content and source in the substrate. The
      aim of this study was to verify the mycelial growth of A. brasiliensis in
      different ammonium sulfate and (or) urea concentrations added to cassava fiber
      and different carbon-to-nitrogen (C:N) ratios to increase the efficiency of
      axenic cultivation. Two nitrogen sources (urea and (or) ammonium sulfate) added
      to cassava fiber were tested for the in vitro mycelial growth in different C:N
      ratios (ranging from 2.5:l to 50:l) in the dark at 28 degrees C. The radial
      mycelial growth was measured after 8 days of growth and recorded photographically
      at the end of the experiment. Nitrogen from urea enhanced fungal growth better
      than ammonium sulfate or any mixture of nitrogen. The best C:N ratios for fungal
      growth were from 10:l to 50:l; C:N ratios below 10:l inhibited fungal growth.

PMID- 17496960
TI  - Acetylation and nitrosation of ciprofloxacin by environmental strains of
      mycobacteria.
AB  - To determine the ability of environmental bacteria to metabolize the frequently
      prescribed fluoroquinolone drug ciprofloxacin, eight Mycobacterium spp. cultures
      were grown for 4 days in a medium containing sorbitol and yeast extract with 100
      mg x L(-1) ciprofloxacin. After the cultures had been centrifuged and the
      supernatants extracted with ethyl acetate, two metabolites were purified by using
      high-performance liquid chromatography. They were identified with liquid
      chromatography/electrospray ionization mass spectrometry and proton nuclear
      magnetic resonance spectroscopy. Ciprofloxacin was transformed to both N
      acetylciprofloxacin (2.5%-5.5% of the total peak area at 280 nm) and N
      nitrosociprofloxacin (6.0%-8.0% of the peak area) by Mycobacterium gilvum PYR-GCK
      and Mycobacterium sp. PYR100 but it was transformed only to N-acetylciprofloxacin
      by Mycobacterium frederiksbergense FAn9, M. gilvum ATCC 43909, M. gilvum BB1,
      Mycobacterium smegmatis mc2155, Mycobacterium sp. 7E1B1W, and Mycobacterium sp.
      RJGII-135. The results suggest that biotransformation may serve as a
      ciprofloxacin resistance mechanism for these bacteria.

PMID- 17496961
TI  - Agrobacterium-mediated insertional mutagenesis of the ochratoxigenic fungus
      Aspergillus westerdijkiae.
AB  - Aspergillus westerdijkiae is a potent ochratoxin A (OTA) producer that has been
      found in coffee beans. OTA is known to have nephrotoxic effects and carcinogenic
      potential in animal species. Here we report for the first time the Agrobacterium
      mediated transformation for Aspergillus westerdijkiae and the generation of
      ochratoxin-defective mutants. Conidia were transformed to hygromycin B resistance
      using strain AGL-1 of Agrobacterium tumefaciens. The obtained transformation
      frequency was up to 47 transformants per 10(6) target conidia. Among 600
      transformants, approximately 5% showed morphological variations. Eight
      transformants with consistently reduced OTA production were obtained. Two of
      these transformants did not produce OTA (detection limit: 0.1 microg/kg); the
      other six mutants produced lower amounts of OTA (1%-32%) compared with the wild
      type strain. By using thermal asymmetric interlaced polymerase chain reaction, we
      successfully identified a putative flavin adenine dinucleotide monooxygenase
      gene.

PMID- 17496962
TI  - Transgenic sequences are frequently lost in Phytophthora parasitica transformants
      without reversion of the transgene-induced silenced state.
AB  - Little data exist on the mechanism and stability of transformation in
      Phytophthora parasitica, a major oomycete parasite of plants. Here, we studied
      the stability of drug-resistant protoplast transformants by analyzing single
      zoospore derivatives. We show that the transgenic sequences are not stably
      integrated into the chromosomes, resulting in the loss of drug resistance in
      single-zoospore derivatives. However, in strains where the P. parasitica gene
      encoding the CBEL elicitor was silenced by transformation with sense or antisense
      constructs, silencing is not reversed when the transgenic sequences are lost.
      This suggests that instability of P. parasitica transformants is not an obstacle
      for loss-of-function studies in this organism.

PMID- 17496963
TI  - Photoperiod regulates elicitation of growth promotion but not induced resistance
      by plant growth-promoting rhizobacteria.
AB  - For several years, we have noticed that plant growth-promoting rhizobacteria
      (PGPR), which consistently promote plant growth in greenhouse tests during
      spring, summer, and fall, fail to elicit plant growth promotion during the
      midwinter under ambient light conditions. This report tests the hypothesis that
      photoperiod regulates elicitation of growth promotion and induced systemic
      resistance (ISR) by PGPR. A commercially available formulation of PGPR strains
      Bacillus subtilis GB03 and Bacillus amyloliquefaciens IN937a (BioYield) was used
      to grow tomato and pepper transplants under short-day (8 h of light) (SD) and
      long-day (12 h of light) (LD) conditions. Results of many experiments indicated
      that under LD conditions, BioYield consistently elicited significant increases in
      root and shoot mass as well as in several parameters of root architecture.
      However, under SD conditions, such increases were not elicited. Differential root
      colonization of plants grown under LD and SD conditions and changes in leachate
      quality partially account for these results. BioYield elicited ISR in tomato and
      pepper under both LD and SD conditions, indicating that although growth promotion
      was not elicited under SD conditions, induced resistance was. Overall, the
      results indicate that PGPR-mediated growth promotion is regulated by photoperiod,
      while ISR is not.

PMID- 17496964
TI  - Differential expression of Rho1GTPase and Rho3GTPase during isotropic and
      polarized growth of Mucor circinelloides.
AB  - Evidence has been obtained that indicates the presence of small 22 kDa GTP
      binding Rho proteins through ADP-ribosylation by Clostridium botulinum C3
      exotoxin in Mucor circinelloides. Rho protein was detected at all stages of
      growth studied. During polarized growth, both under aerobic conditions and during
      the yeast-mycelia transition, the radiolabeling of the [32P]ADP-ribosylated
      protein increased when tube formation occurred and decreased as the hyphae
      branched. However, when Mucor grew isotropically, the Rho protein band was thick
      and its intensity did not vary significantly even after bud formation and
      separation of daughter cells. Crude extracts of yeast and mycelial cells
      exhibited a broad 22 kDa band of the [32P]ADP-ribosylated Rho protein that was
      resolved into a protein with a pI of 6.0, after two-dimensional electrophoresis,
      corresponding to the Rho1p homolog. Furthermore, [32P]ADP-ribosylated Rho protein
      from soluble and particulate extracts of multipolarized mycelial cells obtained
      from the yeast-mycelia transition was separated into two proteins with pI of 6.0
      and 6.4, respectively, after two-dimensional electrophoresis. These correspond to
      the Rho1p and Rho3p homologs, respectively. Therefore, our results show that an
      increase in Rho accumulation is associated with polarized growth.

PMID- 17496965
TI  - Chemical modification results in hyperactivation and thermostabilization of
      Fusarium solani glucoamylase.
AB  - Chemical modification of carboxyl groups of glucoamylase from a mesophilic
      fungus, Fusarium solani, was carried out using ethylenediamine as nucleophile in
      the presence of water-soluble 1-ethyl-3(3-dimethylaminopropyl)carbodiimide.
      Modification brought about a dramatic enhancement of catalytic activity and
      thermal stability of glucoamylase. Temperature and pH optima of ethylenediamine
      coupled glucoamylase (ECG) increased as compared with those of native enzyme. The
      specificity constant (k(cat)/K(m)) of native, ECG-2, ECG-11, and ECG-17 was 136,
      173, 225, and 170, respectively, at 55 degrees C. The enthalpy of activation
      (Delta H*) and free energy of activation (Delta G*) for soluble starch hydrolysis
      were lower for the chemically modified forms. All of the modified forms were
      stable at higher temperatures and possessed high Delta G* against thermal
      unfolding. The effects of alpha-chymotrypsin and subtilisin on the modified forms
      were activating as compared with native. Moreover, denaturation of ECG-2, ECG-11,
      and ECG-17 in urea at 4 mol x L(-1) also showed an activation trend. A possible
      explanation for the thermal denaturation of native and increased thermal
      stability of ECG-2, ECG-11, and ECG-17 at higher temperatures is also discussed.

PMID- 17496966
TI  - Gene cloning and heterologous expression of a serine protease from Streptomyces
      fradiae var.k11.
AB  - The gene sfp1, which encodes a predicted serine proteinase designated SFP1, was
      isolated by the screening of a gene library of the feather-degrading strain
      Streptomyces fradiae var.k11. The open reading frame of sfp1 encodes a protein of
      454 amino acids with a calculated molecular mass of 46.19 kDa. Sequence analysis
      reveals that SFP1 possesses a typical pre-pro-mature organization that consists
      of a signal sequence, an N-terminal propeptide region, and a mature proteinase
      domain. The pre-enzyme of SFP1 was expressed in Escherichia coli and consequently
      purified. The 25.6 kDa fraction with protease activity separated by gel
      filtration chromatography indicated that the mature enzyme of SFP1 was formed by
      autolysis of the propeptide after its expression. The purified SFP1 is active
      under a broad range of pH and temperature. SFP1 has pH and temperature optima of
      pH 8.5 and 65 degrees C for its caseinolytic activity and pH 9 and 62 degrees C
      for its keratinolytic activity. SFP1 was sharply inhibited by the serine
      proteinase inhibitor phenylmethyl sulfonyl fluoride and exhibited a good
      stability to solvents, detergents, and salts. Comparison of the protease activity
      of SFP1 with other commercial proteases indicates that SFP1 has a considerable
      caseinolytic and keratinolytic activity as does proteinase K.

PMID- 17496967
TI  - Potential of plant extracts in combination with bacterial antagonist treatment as
      biocontrol agent of red rot of sugarcane.
AB  - Plant extracts and antifungal microorganisms were tested singly and in
      combination for biocontrol of sugarcane red rot disease (Colletotrichum falcatum)
      using two sugarcane (Saccharum officinarum L.) cultivars, CoC671 and CoC92061, in
      pot and field experiments. Leaf extracts of Abrus precatorius and Bassia
      latifolia and the rhizome extract of Curcuma longa reduced Colletotrichum
      falcatum mycelial growth by 80%, 58%, and 57%, respectively. Although sugarcane-
      planting materials (setts) treated individually with either Pseudomonas
      fluorescens Md1 or A. precatorius in pot experiments had the lowest incidences of
      red rot, 20.1% and 24.2%, respectively, none of the plant extracts were effective
      in the field. In contrast, when the two varieties were tested separately in two
      field locations, the setts treated with A. precatorius in combination with a
      spray or soil application of P. fluorescens Md1 had the lowest incidence of red
      rot in both locations, e.g., 3.1% and 3.4% incidence for CoC92061 in one
      location, and had a similar response to the chemical control. The results suggest
      the applicability of plant-based extracts for the suppression of sugarcane red
      rot disease in the field as an environment-friendly tool in combination with
      antagonists.

PMID- 17496968
TI  - Role of chitinase and beta-1,3-glucanase activities produced by a fluorescent
      pseudomonad and in vitro inhibition of Phytophthora capsici and Rhizoctonia
      solani.
AB  - A study was conducted to investigate the possibility of involvement of chitinase
      and beta-1,3-glucanase of an antagonistic fluorescent Pseudomonas in growth
      suppression of phytopathogenic fungi, Phytophthora capsici and Rhizoctonia
      solani. Fluorescent Pseudomonas isolates GRC(3) and GRC(4) were screened for
      their antifungal potential against phytopathogenic fungi by using dual culture
      technique both on solid and liquid media. The percent inhibition was calculated.
      Various parameters were monitored for optimization of enzyme activities by
      fluorescent Pseudomonas GRC(3). The involvement of chitinases, beta-1,3
      glucanases, and antifungal metabolites of nonenzymatic nature was correlated with
      the inhibition of P. capsici and R. solani. The results provide evidence for
      antibiosis as a mechanism for antagonism. The study also confirms that multiple
      mechanisms are involved in suppressing phytopathogens as evidenced by the
      involvement of chitinase and beta-1,3-glucanase in inhibition of R. solani but
      not P. capsici by isolate GRC3.

PMID- 17496969
TI  - Bioformulation of Burkholderia sp. MSSP with a multispecies consortium for growth
      promotion of Cajanus cajan.
AB  - The present work was undertaken to formulate an effective bioformulation using
      Burkholderia sp. strain MSSP, a known plant-growth-promoting rhizobacterium. MSSP
      was tagged with the reporter gene of green fluorescent protein (gfp) to monitor
      its population in cost-effective solid carriers, including sugarcane-bagasse,
      sawdust, cocoa peat, rice husk, wheat bran, charcoal, and rock phosphate, and
      paneer-whey as liquid carrier. Physical and chemical properties of different low
      cost carrier materials were studied. The viability of the green fluorescent
      tagged variant of MSSP was estimated in different sterile carrier materials. Whey
      and wheat bran proved to be efficient carrier materials for the bioformulation.
      Sawdust, rock phosphate, rice husk, and cocoa peat were average, while charcoal
      and sugarcane-bagasse proved to be inferior carriers. The viability of strain
      MSSP was also assessed in wheat bran and whey-based consortium, having three
      other bacterial strains, namely Sinorhizobium meliloti PP3, Rhizobium
      leguminosarum Pcc, and Bacillus sp. strain B1. Presence of other plant-growth
      promoting bacteria did not have any detrimental effect on the viability of MSSP.
      Efficiency of the wheat-bran-based multispecies consortium was studied on the
      growth of pigeonpea in field conditions. A considerable increase in plant
      biomass, nodule number and weight, and number of pods was recorded as compared
      with individual trials and with the control.

PMID- 17496971
TI  - Effect of water activity and temperature on growth of Penicillium citreoviride
      and Penicillium citrinum on MiGao (rice cake).
AB  - Contamination by mold is a serious problem in steam-cooked rice cake, a
      traditional Chinese food. Growth responses to different temperatures and water
      activity values for Penicillium citreoviride and Penicillium citrinum, two of the
      most common molds, were investigated. Partial least square regression analysis
      showed that the growth of the two fungi did not differ in response to changes in
      water activity and temperature. Optimum water activity for growth was 0.90 and
      optimum temperatures for growth were 30 degrees C in most cases.

PMID- 17496970
TI  - Induction and characterization of morphologic mutants in a natural Saccharomyces
      cerevisiae strain.
AB  - Saccharomyces cerevisiae is a good model with which to study the effects of
      morphologic differentiation on the ecological behaviour of fungi. In this work,
      33 morphologic mutants of a natural strain of S. cerevisiae, obtained with UV
      mutagenesis, were selected for their streak shape and cell shape on rich medium.
      Two of them, showing both high sporulation proficiency and constitutive
      pseudohyphal growth, were analysed from a genetic and physiologic point of view.
      Each mutant carries a recessive monogenic mutation, and the two mutations reside
      in unlinked genes. Flocculation ability and responsiveness to different stimuli
      distinguished the two mutants. Growth at 37 degrees C affected the cell but not
      the colony morphology, suggesting that these two phenotypes are regulated
      differently. The effect of ethidium bromide, which affects mitochondrial DNA
      replication, suggested a possible "retrograde action" of mitochondria in
      pseudohyphal growth.

PMID- 17496972
TI  - Expression of CaPTC7 is developmentally regulated during serum-induced
      morphogenesis in the human fungal pathogen Candida albicans.
AB  - Type 2C protein phosphatases (PP2C) represent a diversified protein phosphatase
      family and play various roles in cells. We previously identified and
      characterized a novel PP2C phosphatase encoded by the CaPTC7 gene in the human
      fungal pathogen Candida albicans. The CaPtc7p has 365 amino acids with a PP2C
      core domain at the C terminus and an additional 116-residue N-terminal sequence
      containing a mitochondrion-targeting sequence. Here, we show that CaPtc7p is
      indeed localized in the mitochondrion, the only eukaryotic PP2C phosphatase that
      has been directly shown to reside in the mitochondrion, suggesting its potential
      role in the regulation of mitochondrial physiology. Furthermore, we show that the
      expression of CaPTC7 at both transcriptional and protein levels is
      developmentally regulated during the serum-induced morphogenesis of C. albicans
      cells. However, disruption of the two alleles of CaPTC7 does not affect cell
      viability or filamentous development in C. albicans.

PMID- 17496973
TI  - Optimization of laccase production from Trametes versicolor by solid
      fermentation.
AB  - The regulation of culture conditions, especially the optimization of substrate
      constituents, is crucial for laccase production by solid fermentation. To develop
      an inexpensive optimized substrate formulation to produce high-activity laccase,
      a uniform design formulation experiment was devised. The solid fermentation of
      Trametes versicolor was performed with natural aeration, natural substrate pH
      (about 6.5), environmental humidity of 60% and two different temperature stages
      (at 37 degrees C for 3 days, and then at 30 degrees C for the next 17 days). From
      the experiment, a regression equation for laccase activity, in the form of a
      second-degree polynomial model, was constructed using multivariate regression
      analysis and solved with unconstrained optimization programming. The optimized
      substrate formulation for laccase production was then calculated. Tween 80 was
      found to have a negative effect on laccase production in solid fermentation; the
      optimized solid substrate formulation was 10.8% glucose, 27.7% wheat bran, 9.0%
      (NH4)2SO4, and 52.5% water. In a scaled-up verification of solid fermentation at
      a 10 kg scale, laccase activity from T. versicolor in the optimized substrate
      formulation reached 110.9 IU/g of dry mass.

PMID- 17496974
TI  - Insight into heterogeneity in cell-surface hydrophobicity and ability to degrade
      hydrocarbons among cells of two hydrocarbon-degrading bacterial populations.
AB  - The sequential bacterial adherence to hydrocarbons (BATH) of successive
      generations of hydrophobic fractions of Paenibacillus sp. R0032A and Burkholderia
      cepacia gave rise to bacterial populations of increasing cell-surface
      hydrophobicity. Thus, hydrophobicity of the first generation (H1) was less than
      that of the second generation (H2), which was less than that of the third
      generation (H3). Beyond H3, the hydrophobic populations became less stable and
      tended to lyse in hexadecane after violent (vortex) agitation, resulting in an
      apparent decline in BATH value. The exhaustively fractionated aqueous-phase
      population (L) was very hydrophilic. The overall cell-surface distribution of the
      population was L < parental strain < H1 < H2 < H3. The ability to degrade crude
      oil, hexadecane, or phenanthrene matched the degree of cell-surface
      hydrophobicity: L < P < H1 < H2 < H3. Thus, in natural populations of hydrocarbon
      degrading Paenibacillus sp. R0032A and B. cepacia, there is a heterogeneity in
      the hydrophobic surface characteriistics that affects the ability of cells to use
      various hydrocarbon substrates.

PMID- 17496975
TI  - Importance of flagella and enterotoxins for Aeromonas virulence in a mouse model.
AB  - A genetic characterization of eight virulence factor genes, elastase, lipase,
      polar flagella (flaA/flaB, flaG), lateral flagella (lafA), and the enterotoxins
      alt, act, and ast, was performed using polymerase chain reaction with 55 drinking
      water and nine clinical isolates. When 16 Aeromonas hydrophila strains, seven
      Aeromonas veronii strains, and seven Aeromonas caviae strains exhibiting
      different combinations of virulence factor genes were tested in immunocompromised
      mice by intraperitoneal injection, only those strains that had one or more of the
      enterotoxins flaA, flaB, and either flaG or lafA showed signs of being virulent.
      The correlation was seen in 97% (29/30) of the strains, which included strains
      from drinking water. Thus, Aeromonas water isolates have the potential to be
      pathogenic in immunocompromised hosts.

PMID- 17496976
TI  - Mycoplasmal membrane protein p37 promotes malignant changes in mammalian cells.
AB  - Evidence of Mycoplasma hyorhinis infection in human gastric cancer tissues has
      been found in previous work. In this study, we demonstrate that the expression of
      p37, a membrane lipoprotein of M. hyorhinis, in mammalian cells induces
      antisenescence, enhances clonogenicity in soft agar, and co-operates with human
      epidermal growth factor receptor-related 2 to inhibit cell adhesion. Conversely,
      truncated p37 protein, with the first 28 amino acids deleted from its N terminal,
      promotes cell senescence. Taken together, our findings suggest that p37 promotes
      malignant changes in mammalian cells. With the identification of this molecular
      component, which is responsible for mycoplasma malignancy-promoting activity, it
      is possible that a better understanding of the relationship between M. hyorhinis
      infection and human gastric cancers will lead to novel diagnostics and
      therapeutics.

PMID- 17496977
TI  - Comparison of rhizobia that nodulate Medicago laciniata and Medicago truncatula
      present in a single Tunisian arid soil.
AB  - The rhizobia present in a single arid region Tunisian soil that nodulate Medicago
      laciniata and Medicago truncatula were compared. All isolates, 40 from each host,
      were Sinorhizobium meliloti based on 16S rRNA polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) patterns and subsequent
      confirmation by sequence analysis of the 16S rRNA genes in four representatives
      from each host species. There was no apparent relationship between Medicago host
      species of isolation and the nodulating rhizobial genome as determined by
      repetitive extragenic palandromic PCR. The isolates of M. laciniata were
      distinguished from those of M. truncatula present in the same soil by variation
      in PCR-RFLP of nifDK, indicating that this dissimilarity is originally genetic
      and not geographic. While forming effective symbioses with their own respective
      isolates, both M. laciniata and M. truncatula formed ineffective true nodules,
      nodule-like structures, or no nodules at all in cross-inoculation tests, as
      confirmed by the histological observations.

PMID- 17496978
TI  - Purification and partial amino acid sequence of thuricin S, a new anti-Listeria
      bacteriocin from Bacillus thuringiensis.
AB  - We report the isolation and characterization of a new bacteriocin, thuricin S,
      produced by the Bacillus thuringiensis subsp. entomocidus HD198 strain. This
      antibacterial activity is sensitive to proteinase K, is heat-stable, and is
      stable at a variety of pH values (3-10.5). The monoisotopic mass of thuricin S
      purified by high performance liquid chromatography, as determined with mass
      spectrometry ESI-TOF-MS, is 3137.61 Da. Edman sequencing and NanoESI-MS/MS
      experiments provided the sequence of the 18 N-terminal amino acids.
      Interestingly, thuricin S has the same N-terminal sequence (DWTXWSXL) as
      bacthuricin F4 and thuricin 17, produced by B. thuringiensis strains BUPM4 and
      NEB17, respectively, and could therefore be classified as a new subclass IId
      bacteriocin.

PMID- 17496979
TI  - Exploring the diversity of marine-derived fungal polyketide synthases.
AB  - Using an approach based on polymerase chain reaction (PCR), we examined the
      diversity of polyketide synthase (PKS) genes present in 160 marine fungal
      isolates, representing 142 species. We obtained ketosynthase (KS) domain PCR
      products from 99 fungal isolates, representing Dothideomycetes, Sordariomycetes,
      Eurotiomycetes, and incertae sedis. Sequence similarity searches and phylogenetic
      analysis of 29 marine partial-KS-encoding sequences revealed domains predicted to
      encode reducing, nonreducing, and 6-methylsalicylic acid PKSs. Bioinformatic
      analysis of an alignment of the KS sequences from marine-derived fungi revealed
      no unique motifs in this region. However, several specificity-determining
      positions were apparent between fungal 6-methylsalicylic acid PKSs as compared
      with either reducing or nonreducing PKSs. Evaluation of these positions in the
      context of a modelled three-dimensional protein structure highlighted their
      potential use as PKS classification markers. Evaluating primer-binding sites was
      necessary to obtain KS domain fragments from putative PKSs while maintaining a
      level of sequence information adequate to properly classify and characterize
      them.

PMID- 17496980
TI  - Studies on uroporphyrinogen decarboxylase from Chlorella kessleri
      (Trebouxiophyceae, Chlorophyta).
AB  - Uroporphyrinogen decarboxylase (UroD) (EC 4.1.1.37) is an enzyme from the
      tetrapyrrole biosynthetic pathway, in which chlorophyll is the main final product
      in algae. This is the first time that a study on UroD activity has been performed
      in a green alga (Chlorella). We isolated and partially purified the enzyme from a
      Chlorella kessleri (Trebouxiophyceae, Chlorophyta) strain (Copahue, Neuquen,
      Argentina), and describe for the first time some of its properties. In C.
      kessleri, the decarboxylation of uroporphyrinogen III occurs in two stages, via 7
      COOH and then 6 and 5 COOH intermediates, with the decarboxylation of the 7 COOH
      compound being the rate-limiting step for the reaction. Cultures in the
      exponential growth phase showed the highest specific activity values. The most
      suitable conditions to measure UroD activity in C. kessleri were as follows: 0.23
      0.3 mg protein/mL, approximately 6-8 micromol/L uroporphyrinogen III, and 20 min
      incubation time. Gel filtration chromatography and Western blot assays indicated
      that UroD from C. kessleri is a dimer of approximately 90 kDa formed by species
      of lower molecular mass, which conserves enzymatic activity.

PMID- 17496981
TI  - Decoloration of Amaranth by the white-rot fungus Trametes versicolor. Part I.
      Statistical analysis.
AB  - The white-rot fungus Trametes versicolor decolorized the mono-azo-substituted
      naphthalenic dye Amaranth. The relationship between the amount of enzymes present
      in the system and the efficiency of the decoloration process was investigated.
      The two responses used to quantify the process of decoloration (i.e., initial
      decoloration rate, v0, and the percent concentration of dye decolorized in 1 h,
      %c) were correlated with the amount of three enzymes considered for the study
      (lignin peroxidase, manganese peroxidase, and laccase) and analyzed through
      stepwise regression analysis (forward, backward, and mixed). The results of the
      correlation analysis and those of the regression analysis indicated that lignin
      peroxidase is the enzyme having the greatest influence on the two responses.

PMID- 17496982
TI  - Decoloration of Amaranth by the white-rot fungus Trametes versicolor. Part II.
      Verification study.
AB  - The involvement of lignin peroxidase (LiP) in the decoloration of the mono-azo
      substituted napthalenic dye Amaranth was investigated with pure enzymes and whole
      cultures of Trametes versicolor. The verification study confirmed that LiP has a
      direct influence on the initial decoloration rate and showed that another enzyme,
      which does not need hydrogen peroxide to function and is not a laccase, also
      plays a role during decoloration. These results confirm the results of a previous
      statistical analysis. Furthermore, the fungal mycelium affects the performance of
      the decoloration process.

PMID- 17496984
TI  - Oral Health Manpower - What are Ghana's requirements?

PMID- 17496983
TI  - Utilizing IL-12, IL-15 and IL-7 as Mucosal Vaccine Adjuvants.
AB  - In this paper we review and discuss three of the most exciting and promising
      cytokines for therapeutic intervention and immunomodulation of immune responses
      including those on mucosal surfaces. The main properties of IL-12, IL-15 and IL-7
      are described and the studies utilizing these cytokines as immunomodulators and
      vaccine adjuvants discussed.

PMID- 17496985
TI  - Options for types of dental health personnel to train for ghana.
AB  - SUMMARY OBJECTIVES: To explore the degree of agreement on issues surrounding the
      proposals for dental health personnel requirements among key oral health
      personalities who are central to determining policy on oral health personnel
      requirements for Ghana and to make recommendations to assist in the future
      development of dental health personnel requirements. DESIGN: A review of the
      literature, published documents and in-depth semi-structured interviews. SETTING:
      Dental health service in Ghana PARTICIPANTS: Key oral health personalities who
      are central to determining policy on oral health personnel requirements for Ghana
      RESULTS: There was a lack of consensus regarding key aspects of planning
      personnel requirements including the numbers and the kinds of professionals
      complementary to dentistry (PCDs) to develop, who should be responsible for their
      training, and which people to admit as trainees of PCDs. CONCLUSION: Greater
      discussion between the various agencies involved should take place to help ensure
      consensus on the overall policy objectives.

PMID- 17496986
TI  - Human pulmonary infections with bovine and environment (atypical) mycobacteria in
      jos, Nigeria.
AB  - SUMMARY OBJECTIVES: To examine sputum specimens from patients with persistent
      bronchopulmonary disorders for mycobacterium species and to characterize the
      recovered isolates with a view to determining the extent of involvement of
      environmental mycobacteria in pulmonary infections. DESIGN: Analytical study
      using standard microscopy, culture and biochemical test for the identification of
      mycobacterium species. SETTING: Jos University Teaching Hospital (JUTH) and 2
      referral hospitals: Plateau Specialist Hospital and Evangelical Churches of West
      Africa (ECWA) Evangel Hospital in Jos, Nigeria. PARTICIPANTS: Three hundred and
      twenty nine (329) volunteer new patients seen at the chest clinic and general out
      patient departments with broncho-pulmonary disorders. Patients already on anti
      tuberculosis were excluded from the study. INTERVENTIONS: Subjects were
      administered antituberculosis drugs and or other treatment regimes after proper
      diagnosis RESULTS: Sixty-five (65) mycobacterial isolates were obtained and
      differentiated into human tubercle bacilli, bovine and or environmental
      (atypical) mycobacteria on the basis of nine identification tests. Of the 65
      mycobacterial isolates subjected to the tests, 40 (61.54%) were identified as
      mycobacterium tuberculosis, 10 (15.38%) as M. bovis and 15 (23.08%) as
      environmental mycobacteria. Among the environmental group, 9 (20.69%) were
      classified as M. avium 3 (3.45%) each as M. kansasi and M. fortuitum.
      CONCLUSIONS: The study confirms the involvement of bovine and environmental
      mycobacteria in pulmonary infections. This may be related to the rising
      prevalence of HIV/AIDS globally. The need for adequate bacteriological analysis
      in current-day diagnosis of pulmonary tuberculosis in indicated.

PMID- 17496987
TI  - Surveillance of viral haemorrhagic fevers in ghana: entomological assessment of
      the risk of transmission in the northern regions.
AB  - SUMMARY OBJECTIVES: To assess the risk of transmission of viral haemorrhagic
      fevers in northern Ghana. DESIGN: A two-year cross-sectional entomological study
      was carried out in four communities in the northern part of Ghana. Standard WHO
      methods were used to collect adult and larvae of Aedes mosquitoes to estimate man
      vector contact rates and larval indices. RESULTS: A total of 2804 households were
      surveyed to estimate larval indices and man-vector contacts of potential vectors
      of viral haemorrhagic fevers such as Yellow fever and Dengue. Over 56% households
      in each study site were positive for Aedes larvae. Relatively higher Breteaux
      index (BI) and Container index (CI) were estimated in Damongo (BI: 180 and CI:
      44.8) and Jirapa (BI: 149.7 and CI: 41.5) compared to Tumu (BI: 76.1 and CI:
      19.5) and Bolgatanga (BI: 72.4 and CI: 20.6). Man-biting rates of 9.8 and 18.5
      bites /man/hour were estimated for Damongo and Jirapa respectively whilst
      Bolgatanga recorded 10 B/M/H. Generally, man-vector contact rates in all the
      study sites were higher during the dry season than the wet season. Larval indices
      showed seasonal variations and the dry season was identified as the high-risk
      period for transmission of viral haemorrhagic fevers and possible disease
      outbreaks. No flavivirus was detected in the 2034 Aedes mosquitoes from the study
      sites by RT-PCR. CONCLUSIONS: Aedes mosquito larval densities and adult biting
      rates, in all the study areas were sufficient to promote outbreaks of viral
      haemorrhagic fevers.

PMID- 17496988
TI  - Ten years of preoperative autologous blood donation in accra.
AB  - SUMMARY BACKGROUND: Preoperative autologous blood donation (PABD) is utilized to
      circumvent the use of allogenic blood for various reasons. OBJECTIVE: To describe
      the distribution in terms of demographic characteristic, trends in participation
      and result of screening test of the PABD programme of the Accra Area Blood Center
      from 1993-2003. DESIGN AND SETTING: Retrospective descriptive study of PABD in
      patients scheduled for a variety of elective surgical procedures. SETTING:
      Different levels of institutional health care in Accra, Ghana. METHODS: Data from
      existing records of patients who had participated in PABD were collated and
      analyzed RESULTS: Five hundred and forty six (546) females and 89 males
      participated, with ages ranging between 14-74 years. Majority of the patients
      (76.7%) underwent gynaecological surgery. A total of 330 (52%) donated one unit
      only, and 299 (47.1%) donated two units. Majority of the patients (56.4%) had the
      surgery at the Korle-Bu Teaching Hospital (KBTH). Of the donations, 21 (3.3%), 1
      (0.2%), 1 (0.3%) and nil were positive for HBV, HIV I & II, HCV and VDRL
      respectively. A total of 848 (89.4%) autologous cross-matched units were issued
      out. There was a steady progressive increase in participation. CONCLUSION: Mainly
      adult females scheduled for gynaecological surgeries in KBTH participated, while
      almost equal proportions donated one or two units of blood which meets the blood
      needs of most elective surgeries. Therefore healthy patients going for elective
      surgeries in regions with limited blood supply must be encouraged to enter a PABD
      Programme. Further studies in this field should evaluate motivational factors for
      participation.

PMID- 17496989
TI  - Classical cornelia de lange syndrome.
AB  - SummaryThese two case reports illustrate the importance of doing a thorough
      dysmorphology examination for all so called "Multiple congenital anomalies"
      children and attempting to fit them into a recognized syndrome. Well over 2000
      dysmorphic syndromes are now recognized and diagnosis of these children can be
      extremely difficult.

PMID- 17496990
TI  - Concurrent malakoplakia of cervical lymph nodes and prostatic adenocarcinoma with
      bony metastasis: case report.
AB  - SummaryAn unusual case of malakoplakia of the cervical lymph nodes in a patient
      with bony metastasis from prostrate cancer is reported. An 80-year-old patient
      with metastatic prostatic cancer presented with bilateral cervical
      lymphadenopathy, and a hard cervical mass in the left supraclavicular region.
      Biopsy of the lymph gland revealed the presence of malakoplakia, with no evidence
      of metastatic prostatic carcinoma. Though co-existence of malakoplakia and
      adenocarcinoma within the prostrate gland has been reported before, this case is
      unique, as it highlights the rare occurrence of malakoplakia involving distant
      nodes in a patient with bony metastatic prostate cancer. This report reflects the
      fact that things are not always what they seem in medicine, and not infrequently
      we come across a different pathology which mimics another.

PMID- 17496991
TI  - A retrospective analysis of vinorelbine chemotherapy for patients with previously
      treated soft-tissue sarcomas.
AB  - Introduction. The role of vinorelbine in specific soft tissue sarcoma subtypes is
      unclear. We present retrospective single institution experience with single-agent
      vinorelbine in subjects with metastatic soft tissue malignancies. Methods. Fifty
      eight patients were treated with single agent intravenous vinorelbine between
      April 1997 and December 2004. Doxorubicin had been administered previously to 53
      subjects (91%), and the median number of lines of previous chemotherapy was 3
      (range 0-7). Results. Patients received a median 6 doses of vinorelbine (range 1
      65). The overall response rate was 6% (3 patients: 1 angiosarcoma, 1 epithelioid
      sarcoma, and 1 embryonal rhabdomyosarcoma). Fourteen patients (26%) experienced a
      best result of stable disease. Median time to progression was 1.8 months (95%
      confidence intervals 1.5-2.1 months, Kaplan-Meier estimate). Eight patients
      experienced grade 3 or 4 toxicity, most commonly febrile neutropenia. Conclusion.
      Vinorelbine demonstrates limited activity in a heavily pretreated group of soft
      tissue sarcoma patients. Prospective investigation may be considered for selected
      sarcoma subtypes.

PMID- 17496992
TI  - Focus on the tumour periphery in MRI evaluation of soft tissue sarcoma:
      infiltrative growth signifies poor prognosis.
AB  - Purpose. Infiltrative microscopical peripheral growth of soft tissue sarcomas
      (STS) has been shown to be of prognostic importance and preoperative risk
      stratification could individualize neoadjuvant treatment. Patients and methods.
      We assessed peripheral tumour growth pattern on preoperative MRI from 78 STS. The
      findings were correlated to histopathology and to outcome. Results. The MRI-based
      peripheral tumour growth pattern was classified as pushing in 34 tumours, focally
      infiltrative in 25, and diffusely infiltrative in 19. All tumours with diffuse
      infiltration on MRI also showed microscopical infiltration, whereas MRI failed to
      identify infiltration in two-thirds of the microscopically infiltrative tumours.
      Diffusely infiltrative growth on MRI gave a 2.5 times increased risk of
      metastases (P = .01) and a 3.7 times higher risk of local recurrence (P = .02).
      Discussion. Based on this observation we suggest that MRI evaluation of STS
      should focus on the peripheral tumour growth pattern since it adds prognostic
      information of value for decisions on neoadjuvant therapies.

PMID- 17496993
TI  - Late-onset meningeal metastases in liposarcoma: a case report and review of the
      literature.
AB  - Intracranial metastases from liposarcoma are rare and almost always preceded by
      the development of systemic tumour spread. We report here a case of liposarcoma
      with spread to the cranial nervous system 23 years after treatment of the primary
      tumour. The literature on brain metastases from soft tissue sarcoma is also
      reviewed.

PMID- 17496994
TI  - Contralateral total hip arthroplasty after hindquarter amputation.
AB  - We describe the management and outcome of a 62-year old lady who developed severe
      osteoarthritis of the hip, nine years after a hindquarter amputation for
      radiation-induced sarcoma of the contralateral pelvis. The difficulties of
      stabilising the pelvis intraoperatively and the problems of postoperative
      rehabilitation are outlined. The operation successfully relieved her pain and
      restored limited mobility.

PMID- 17496995
TI  - Primary intracranial leiomyosarcoma: report of a case and review of the
      literature.
AB  - A 26-year old man presented with a 3-month history of a progressively enlarging
      palpable parieto-occipital mass. A CT scan indicated the lesion arose from the
      dura with bony destruction. A stealth assisted craniotomy was performed with the
      provisional diagnosis of osteoblastic meningioma. Further histopathologic
      analysis of the intracranial mass was consistent with leiomyosarcoma. Staging
      evaluation, including CT and PET scans, demonstrated no other sites of disease.
      Despite complete surgical resection and radiotherapy to the resection site, the
      disease recurred locally and systematically 5 months later. Primary intracranial
      mesenchymal tumors are rare and few cases have been previously reported. Outcomes
      have been universally poor and current therapeutic approaches appear to have only
      limited benefit.

PMID- 17496997
TI  - Improving Outcomes After Relapse in Ewing's Sarcoma: Analysis of 114 Patients
      From a Single Institution.
AB  - The outcome for patients with relapsed Ewing's sarcoma is poor. A retrospective
      analysis was carried out to identify factors associated with improved survival.
      Between 1992 and 2002, 114 patients presented with relapsed or progressive
      disease. Median time to progression/relapse was 13 months (range, 2-128).
      Treatment at relapse included high dose treatment (HDT) in 29 patients, and
      surgery or definitive radiotherapy in 29. 2 and 5-year post relapse survival
      (PRS) was 23.5% and 15.2%, respectively. In multivariate analysis, the most
      significant factors associated with improved survival were disease confined
      locally or to the lungs (2-year PRS, 40% versus 6%; P < .001), relapse > 18
      months from diagnosis (2-year PRS, 53% versus 8%; P < .001), HDT at relapse (2
      year PRS, 62% versus 11%; P < .001), and surgery and/or radiotherapy at relapse
      (2-year PRS, 51% versus 14%; P < .001). First treatment failure in Ewing's
      sarcoma is mostly fatal. Improved survival can be achieved in selective patients
      with aggressive treatment. These improvements are confined to those without bone
      or bone marrow metastases.

PMID- 17496996
TI  - Ecteinascidin-743: evidence of activity in advanced, pretreated soft tissue and
      bone sarcoma patients.
AB  - Purpose. To evaluate the activity and safety of ecteinascidin (ET-743) in
      pretreated patients with advanced or metastatic soft tissue and bone sarcoma.
      Patients or subjects. Eighty-nine patients received ET-743 as a 24-hour
      continuous infusion at a dose of 900-1500 mug/m(2) every 3 weeks. Results. We
      observed one complete remission, 5 partial remissions, one minimal response, and
      16 patients with a disease stabilization of 6 months or more. The objective
      response rate was 6.7% and the clinical benefit rate at 3 and 6 months was 37.7%
      and 23.4%, respectively. Responses were noted in patients with lipo-, leiomyo-,
      osteo-, and myogenic sarcoma, with a median duration of 9.85 months. Toxicity
      mainly involved an asymptomatic elevation of transaminases and neutropenia.
      Estimated 1- and 2-year survival rates were 39.4% and 15.8%. Median overall
      survival was 8.25 months. Discussion. This retrospective analysis confirms that
      ET-743 induces objective responses and progression arrest in a clinically
      relevant proportion of patients.

PMID- 17496998
TI  - Synthesis, characterization, and biotoxicity of N N donor sulphonamide imine
      silicon(IV) complexes.
AB  - The organosilicon derivatives of 2-[1-(2-furayl)ethyledene]sulphathiazole with
      organosilicon chlorides have been synthesised and characterized on the basis of
      analytical, conductance, and spectroscopic techniques. Probable trigonal
      bipyramidal and octahedral structures for the resulting derivatives have been
      proposed on the basis of electronic, IR, (1)H, (13)C NMR, and (29)Si NMR spectral
      studies. In the search for better fungicides, bactericides, nematicides, and
      insecticides studies were conducted to assess the growth-inhibiting potential of
      the synthesized complexes against various pathogenic fungal, bacterial strains,
      root-knot nematode Meloidogyne incognita, and insect Trogoderma granarium. These
      studies demonstrate that the concentrations reached levels which are sufficient
      to inhibit and kill the pathogens, nematode, and insect.

PMID- 17496999
TI  - Antispermatogenic activity of the benzothiazoline ligand and corresponding
      organoantimony(V) derivative in male albino rats.
AB  - Triphenylantimony(V) derivative, Ph(3)Sb(OPr(i)) [SC(6)H(4)N :
      C(CH(3))CH(2)C(O)CH(3)], 1b, and the corresponding benzothiazoline ligand [1, 2],
      HNC(6)H(4)SC(CH(3))CH(2)C(O)CH(3), 1a, have been tested for their effects on the
      reproductive system of male albino rats. The oral administration of both 1a and
      1b at the dose level of 10 mg/rat/day produced significant reduction in the
      weights of testes, epididymides, seminal vesicles, and ventral prostate.
      Significant decrease in sperm motility as well as in sperm density resulted in
      100% sterility. Significant (P < .01) alterations were also found in biochemical
      parameters of reproductive organs in treated male rats as compared to the control
      group. Production of preleptotene, pachytene, and secondary spermatocytes was
      decreased by 42%, 43%, 39%, and by 44%, 49%, 55% in the ligand, 1a, and
      organoantimony(V) derivative, 1b, treated rats, respectively. These results
      indicate that both compounds 1a and 1b are antispermatogenic in nature and on
      oral administration in male rats, and finally caused sterility. A comparison
      indicates that the organoantimony(V) derivative 1b is more effective pertaining
      to its antispermatogenic activity than the corresponding ligand 1a.

PMID- 17497000
TI  - Fertility regulation in male rats by implemented tetraazamacrocyclic compounds of
      iron(II): synthetic, spectroscopic, and applied aspects with toxicological
      screening.
AB  - Antifertility and histopathological investigations were carried out on
      reproductive organs of male albino rats induced by tetraazamacrocyclic complexes
      of iron(II). The complexes were synthesized by the template condensation of 1,2
      diaminoethane, 1,3-diaminopropane with succinic acid and phthalic acid in 2 : 2
      molar ratios which are abbreviated as [Fe(TAML(n))OAc] (n = 1 or 2 and TAML(n)
      represents tetraazamacrocyclic ligand). The complexes have been characterized by
      elemental analysis, conductivity measurements, IR, and electronic spectra.

PMID- 17497001
TI  - Effect of benzothiazoline ligand and corresponding organoantimony(V) derivative
      on the reproductive system of male rats.
AB  - Benzothiazoline HNC(6)H(4)SC(C6H5)CH:C(OH)COOCH(3) 1 prepared by the condensation
      reaction of aroyl pyruvate and 2-aminothiophenol has been treated with
      Ph(3)Sb(OPr(i))(2) to yield Ph(3)Sb[SC(6)H(4)NC(C6H5)CH:COCOOCH(3)] 2. These
      compounds have been characterized by elemental analyses and molecular weight
      determinations. The probable structures of the ligand as well as antimony complex
      have been tentatively proposed on the basis of IR and NMR ((1)H and (13)C)
      spectral evidences. Both compounds have been tested for their antifertility
      activity in male albino rats. The oral administration of compounds 1 and 2 at the
      dose level of 10 mg/rat/day significantly reduced the weights of testes,
      epididymides, ventral prostate, and seminal vesicles. The production of
      preleptotene spermatocytes was decreased by 36.57%; 57.23%, pachytene
      spermatocytes by 40.06%; 62.01%, and secondary spermatocytes by 52.45%; 63.22%,
      following the treatment of compounds 1 and 2, respectively. The marked reduction
      in sperm motility and density resulted in infertility by 100%. Significant (P <
      .01) alterations were found in biochemical parameters of reproductive organs in
      treated animals as compared to control group. It is concluded that all these
      effects may finally impair the fertility of male rats.

PMID- 17497002
TI  - Bioinorganic chemistry in thyroid gland: effect of antithyroid drugs on
      peroxidase-catalyzed oxidation and iodination reactions.
AB  - Propylthiouracil (PTU) and methimazole (MMI) are the most commonly used
      antithyroid drugs. The available data suggest that these drugs may block the
      thyroid hormone synthesis by inhibiting the thyroid peroxidase (TPO) or diverting
      oxidized iodides away from thyroglobulin. It is also known that PTU inhibits the
      selenocysteine-containing enzyme ID-1 by reacting with the selenenyl iodide
      intermediate (E-SeI). In view of the current interest in antithyroid drugs, we
      have recently carried out biomimetic studies to understand the mechanism by which
      the antithyroid drugs inhibit the thyroid hormone synthesis and found that the
      replacement of sulfur with selenium in MMI leads to an interesting compound that
      may reversibly block the thyroid hormone synthesis. Our recent results on the
      inhibition of lactoperoxidase (LPO)-catalyzed oxidation and iodination reactions
      by antithyroid drugs are described.

PMID- 17497003
TI  - Synthetic, structural, and biochemical studies of organotin(IV) with Schiff bases
      having nitrogen and sulphur donor ligands.
AB  - Three bidentate Schiff bases having nitrogen and sulphur donor sequences were
      prepared by condensing S-benzyldithiocarbazate (NH(2)NHCS(2)CH(2)C(6)H(5)) with
      heterocyclic aldehydes. The reaction of diphenyltin dichloride with Schiff bases
      leads to the formation of a new series of organotin(IV) complexes. An attempt has
      been made to prove their structures on the basis of elemental analyses,
      conductance measurements, molecular weights determinations, UV, infrared, and
      multinuclear magnetic resonance ((1)H, (13)C, and (119)Sn) spectral studies.
      Organotin(IV) complexes were five- and six-coordinate. Schiff bases and their
      corresponding organotin complexes have also been screened for their antibacterial
      and antifungal activities and found to be quite active in this respect.

PMID- 17497004
TI  - Kinetic study of DNA modification by phthalocyanine derivative of the
      oligonucleotide.
AB  - Design of chemically modified oligonucleotides for regulation of gene expression
      has attracted considerable attention over the last decades. One actively pursued
      approach involves antisense or antigene constructs carrying reactive groups, many
      of these based on transition metal complexes. The complexes of Co(II) with
      phthalocyanines are extremely good catalysts of oxidation of organic compounds
      with molecular oxygen and hydrogen peroxide. In this study, we have investigated
      the kinetics and thermodynamics of sequence-specific modification of DNA with
      deoxyribooligonucleotide linked to Co(II)-tetracarboxyphthalocyanine (PtcCo(II))
      in the presence of H(2)O(2).

PMID- 17497005
TI  - Synthesis, characterization, and cytotoxic activity of new lanthanum(III)
      complexes of bis-coumarins.
AB  - Complexes of lanthanum(III) with bis-coumarins: 3,3'-benzylidene-bis(4-hydroxy-2H
      1-benzopyran-2-one) (H(2)L1) and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol
      3-yl)-methane (H(2)L2) were synthesized by reaction of lanthanum(III) salt and
      the ligands, in amounts equal to metal : ligand molar ratio of 1 : 2. The
      complexes were prepared by adding an aqueous solution of lanthanum(III) salt to
      an aqueous solution of the ligand subsequently raising the pH of the mixture
      gradually to circa 5.0 by adding dilute solution of sodium hydroxide. The
      lanthanum(III) complexes with bis-coumarins were characterized by different
      physicochemical methods-elemental analysis, IR-, (1)H-, and (13)C-NMR
      spectroscopies, and mass spectral data. The spectral data of lanthanum(III)
      complexes were interpreted on the basis of comparison with the spectra of the
      free ligands. This analysis showed that in the La(III) complexes, the ligands
      coordinated to the metal ion through both deprotonated hydroxyl groups. On the
      basis of the nu(C=O) red shift observed, participation of the carbonyl groups in
      the coordination with the metal ion was also suggested. In the present study, we
      performed a cytotoxic-effects screening of the lanthanum complexes with H(2)L1
      and H(2)L2 in a panel of human tumor cell lines, using the standard MTT-dye
      reduction assay for cell viability. The panel consisted of the acute myeloid
      leukemia-derived HL-60 and the chronic myeloid leukemia-derived BV-173. Following
      a 24- hour treatment of BV-173 cells with lanthanum complex of H(2)L1 at 100 or
      200 microM led to a DNA-laddering. The findings suggest that the observed
      cytotoxicity of the lanthanum complex of H(2)L1 on BV-173 is at least partly
      mediated through induction of programmed cell death.

PMID- 17497006
TI  - Synthesis, Biological, Spectral, and Thermal Investigations of Cobalt(II) and
      Nickel(II) Complexes of N-Isonicotinamido -2',4'-Dichlorobenzalaldimine.
AB  - A new series of 12 complexes of cobalt(II) and nickel(II) with N-isonicotinamido
      2',4'-dichlorobenzalaldimine (INH-DCB) with the general composition MX(2) . n(INH
      DCB) [M = Co(II) or Ni(II), X = Cl(-) ,Br(-), NO(3) (-), NCS(-), or CH(3)COO(-),
      n = 2; X = ClO(4) (-), n = 3] have been synthesized. The nature of bonding and
      the stereochemistry of the complexes have been deduced from elemental analyses,
      infrared, electronic spectra, magnetic susceptibility, and conductivity
      measurements. An octahedral geometry has been suggested for all the complexes.
      The metal complexes were screened for their antifungal and antibacterial
      activities on different species of pathogenic fungi and bacteria and their
      biopotency has been discussed.

PMID- 17497007
TI  - New Dihydro OO'Bis(Salicylidene) 2,2' Aminobenzothiazolyl Borate Complexes:
      Kinetic and Voltammetric Studies of Dimethyltin Copper Complex with Guanine,
      Adenine, and Calf Thymus DNA.
AB  - The newly synthesized ligand, dihydro OO'bis(salicylidene) 2,2'
      aminobenzothiazolyl borate (2), was derived from the reaction of Schiff base of 2
      aminobenzothiazole and salicylaldehyde with KBH(4). Cu(II) (3) and Zn(II) (4)
      complexes of (2) were synthesized and further metallated with
      dimethyltindichloride to yield heterobimetallic complexes (5) and (6). All
      complexes have been thoroughly characterized by elemental analysis, and IR, NMR,
      EPR, and UV-Vis spectroscopy and conductance measurements. The spectroscopic data
      support square planar environment around the Cu(II) atom, while the Sn(IV) atom
      acquires pentacoordinate geometry. The interaction of complex (5) with guanine,
      adenine, and calf thymus DNA was studied by spectrophotometric, electrochemical,
      and kinetic methods. The absorption spectra of complex (5) exhibit a remarkable
      "hyperchromic effect" in the presence of guanine and calf thymus DNA. Indicative
      of strong binding of the complex to calf thymus DNA preferentially binds through
      N(7) position of guanine base, while the adenine shows binding to a lesser
      extent. The kinetic data were obtained from the rate constants, k(obs), values
      under pseudo-first-order conditions. Cyclic voltammetry was employed to study the
      interaction of complex (5) with guanine, adenine, and calf thymus DNA. The CV of
      complex (5) in the absence and in the presence of guanine and calf thymus DNA
      altered drastically, with a positive shift in formal peak potential E(pa) and
      E(pc) values and a significant increase in peak current. The positive shift in
      formal potentials with increase in peak current favours strong interaction of
      complex (5) with calf thymus DNA. The net shift in E(1/2) has been used to
      estimate the ratio of equilibrium constants for the binding of Cu(II) and Cu(I)
      complexes to calf thymus DNA.

PMID- 17497009
TI  - Synthesis, Spectral, and Biological Properties of Copper(II) Complexes of
      Thiosemicarbazones of Schiff Bases Derived from 4-Aminoantipyrine and Aromatic
      Aldehydes.
AB  - We have synthesized a novel series of Schiff bases by condensation of 4
      aminoantipyrine and various aromatic aldehydes followed by reaction with
      thiosemicarbazide. These thiosemicarbazones are potential ligands toward
      transition metal ions. The reaction of copper(II) salts with 4[N
      (benzalidene)amino]antipyrinethiosemicarbazone (BAAPTS), 4[N-(4'
      methoxybenzalidene) amino] antipyrinethiosemicarbozone (MBAAPTS), 4[N-(4'
      dimethylamino benzalidene) amino] antipyrinethiosemicarbazone (DABAAPTS), and 4[N
      (cinnamalidene) amino] antipyrinethiosemicarbazone (CAAPTS) resulted in the
      formation of solid complexes with the general composition CuX(2) . (H(2)O)(L)(X =
      Cl, Br,NO(3),NCS, or CH(3)COO; L = BAAPTS, MBAAPTS, DABAAPTS, or CAAPTS). These
      complexes were characterized through elemental analysis, molecular weight,
      electrical conductance, infrared, electronic spectra, and magnetic
      susceptibilities at room temperature. Copper(II) complexes with BAAPTS and
      MBAAPTS were screened for antibacterial and antifungal properties and have
      exhibited potential activity. Thermal stabilities of two representative complexes
      were also investigated.

PMID- 17497008
TI  - Reactions Between Chalcogen Donors and Dihalogens/Interalogens: Typology of
      Products and Their Characterization by FT-Raman Spectroscopy.
AB  - The chemical bond and structural features for the most important classes of solid
      products obtained by reacting chalcogen donors with dihalogens and interhalogens
      are reviewed. Particular attention is paid to the information the FT-Raman
      spectroscopy can confidently give about each structural motif considered in the
      absence of X-ray structural analyses.

PMID- 17497010
TI  - Assessment of Toxicity of Some Penta- and Hexacoordinated Organotin(IV) and
      Tetracoordinated Tin(II) Complexes of Heterocyclic beta-Diketones.
AB  - A number of penta- and hexacoordinated organotin(IV) complexes and
      tetracoordinated tin(II) complexes of compositions Me2SnCl[RCOC:CON(C6H5)N:CCH3]
      (where R = - CH(3), -p-ClC(6)H(4), and -C(6)H(5)), Me2Sn[RCOC:CON(C6H5)N:CCH3]2
      (where R = -CH(3), and -C(6)H(5)), and Sn(II) [RCOC:CON(C6H5)N:CCH3]2 (where R = 
      p-ClC(6)H(4) and -C(6)H(5)) were screened for their toxicity against Musca
      domestica (house fly). In general, organotin(IV) complexes contribute more to the
      activity than tin(II) complexes.

PMID- 17497011
TI  - Interaction of thioamides, selenoamides, and amides with diiodine.
AB  - We review the results of our work on the iodine interaction with thioamides,
      selenoamides, and amides. Complexes with (i) "spoke" or "extended spoke"
      structures, D . I(2) and D . I(2) . I(2), respectively, (D is the ligand donor)
      (ii) iodonium salts of {[D(2) - I](+)[I(n)](-)} (n = 3, 7) and {[D(2) -
      I](+)[FeCl(4)](-)} formulae and (iii) disulfides of the categories (a) [D - D],
      (b) {[D - DH](+)[I(3)](-)} have been isolated and characterized. A compound of
      formula {[D(2) - I](+)[I(3)](-)[D . I(2)]} containing both types of complexes (i)
      and (ii) was also isolated. The interaction of diiodine with selenium analogs of
      the antithyroid drug 6-n-propyl-2-thiouracil (PTU), of formulae RSeU (6-alkyl-2
      Selenouracil) results in the formation of complexes with formulae [(RSeU)I(2)].
      All these results are correlated with the mechanism of action of antithyroid
      drugs. Finally, we review here our work on the diiodine interaction with the
      amides (LO).

PMID- 17497012
TI  - Conjugates of phthalocyanines with oligonucleotides as reagents for sensitized or
      catalytic DNA modification.
AB  - Several conjugates of metallophthalocyanines with deoxyribooligonucleotides were
      synthesized to investigate sequence-specific modification of DNA by them.
      Oligonucleotide parts of these conjugates were responsible for the recognition of
      selected complementary sequences on the DNA target. Metallophthalocyanines were
      able to induce the DNA modification: phthalocyanines of Zn(II) and Al(III) were
      active as photosensitizers in the generation of singlet oxygen (1)O(2), while
      phthalocyanine of Co(II) promoted DNA oxidation by molecular oxygen through the
      catalysis of formation of reactive oxygen species ((.)O(2) (-), H(2)O(2), OH).
      Irradiation of the reaction mixture containing either Zn(II)- or Al(III)
      tetracarboxyphthalocyanine conjugates of oligonucleotide pd(TCTTCCCA) with light
      of > 340 nm wavelength (Hg lamp or He/Ne laser) resulted in the modification of
      the 22-nucleotide target d(TGAATGGGAAGAGGGTCAGGTT). A conjugate of Co(II)
      tetracarboxyphthalocyanine with the oligonucleotide was found to modify the DNA
      target in the presence of O(2) and 2-mercaptoethanol or in the presence of
      H(2)O(2). Under both sensitized and catalyzed conditions, the nucleotides G(13)
      G(15) were mainly modified, providing evidence that the reaction proceeded in the
      double-stranded oligonucleotide. These results suggest the possible use of
      phthalocyanine-oligonucleotide conjugates as novel artificial regulators of gene
      expression and therapeutic agents for treatment of cancer.

PMID- 17497013
TI  - Protective Effect of Meso-Tetrakis-(3,5-di-tert-butyl-4-hydroxyphenyl)porphyrin
      on the In Vivo Impact of Trimethyltin Chloride on the Antioxidative Defense
      System.
AB  - The in vivo effect of trimethyltin chloride (Me(3)SnCl), free base meso
      tetrakis(3,5-di-tert-butyl-4-hydroxyphenyl)porphyrin (R'(4)PH(2)) and their
      equimolar mixture, on the enzymatic activity of catalase (CAT), superoxide
      dismutase (SOD), and on the total content of free sulfhydryl groups has been
      studied in rat liver and kidney. It was demonstrated that the simultaneous
      treatment of tested animals with the combination of Me(3)SnCl and R'(4)PH(2)
      reduced the toxic impact of Me(3)SnCl.

PMID- 17497014
TI  - Structure-Activity Relationships of Synthetic Coumarins as HIV-1 Inhibitors.
AB  - HIV/AIDS pandemics is a serious threat to health and development of mankind, and
      searching for effective anti-HIV agents remains actual. Considerable progress has
      been made in recent years in the field of drug development against HIV. A lot of
      structurally different coumarins were found to display potent anti-HIV activity.
      The current review demonstrates the variety of synthetic coumarins having unique
      mechanism of action referring to the different stages of HIV replication. Recent
      studies based on the account of various synthetic coumarins seem to indicate that
      some of them serve as potent non-nucleoside RT-inhibitors, another as inhibitors
      of HIV-integrase or HIV-protease. The merits of selecting potential anti-HIV
      agents to be used in rational combination drugs design and structure-activity
      relationships are discussed.The scientific community is looking actively for new
      drugs and combinations for treatment of HIV infection effective for first-line
      treatment, as well as against resistant mutants. The investigation on chemical
      anti-HIV agents gives hope and optimism about it. This review article describes
      recent progress in the discovery, structure modification, and structure-activity
      relationship studies of potent anti-HIV coumarin derivatives.

PMID- 17497015
TI  - Pressure-tuning Raman spectra of diiodine thioamide compounds: models for
      antithyroid drug activity.
AB  - The pressure-tuning Raman spectra of five solid, diiodine heterocyclic thioamide
      compounds (mbztS)I(2) (mbztS = N-methyl-2-mercaptobenzothiazole) (1);
      [(mbztS)(2)I](+)[I(7)](-) (2); (pySH)I(2) (pySH = 2-mercaptopyridine) (3);
      [(pySH)(pyS](+)[I(3)](-) (4); (thpm)(I(2))(2) or possibly [(thpm)I(2)](+)[I(3)](
      ) (thpm = 2-mercapto-3,4,5,6-tertahydropyrimidine (5) have been measured for
      pressures up to approximately 50 kbar using a diamond-anvil cell. Compounds 1, 4,
      and 5 undergo pressure-induced phase transitions at approximately 35,
      approximately 25, and approximately 32 kbar, respectively. Following the phase
      transition in 1, the pressure dependences of the vibrational modes, which were
      originally located at 84, 111, and 161 cm(-1) and are associated with the
      S(cdots, three dots, centered)I-I linkage, are 2.08, 1.78, and 0.57 cm(-1)/kbar,
      respectively. These pressure dependences are typical of low-energy vibrations.
      The pressure-tuning FT-Raman results for the pairs of compounds 1 , 2, 3, and 4
      are remarkably similar to each other suggesting that the compounds are most
      probably perturbed diiodide compounds rather than ionic ones. The Raman data for
      5 show that it is best formulated as (thpm)(I(2))(2) rather than
      [(thpm)(2)I](+)[I(3)](-).

PMID- 17497016
TI  - Antihuman Immunodeficiency Virus Type 1 (HIV-1) Activity of Rare Earth Metal
      Complexes of 4-Hydroxycoumarins in Cell Culture.
AB  - The cerium Ce(III), lanthanum La(III), and neodymium Nd(III) complexes with 4
      hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one (warfarin) (W) and 3,3'
      benzylidenebis[4-hydroxycoumarin] (1) were synthesized and studied for the first
      time for cytotoxicity (on MT-2 cells) and as anti-HIV agents under acute and
      chronic infection. The complexes were characterized by different physicochemical
      methods: mass spectrometry, (1)H NMR, (13)C NMR, and IR spectroscopy. The spectra
      of the complexes were interpreted on the basis of comparison with the spectrum of
      the free ligands. Anti-HIV effect of the complexes/ligands was measured in MT-2
      cells by microtiter infection assay. Detection of endogenous reverse
      transcriptase (RT) activity and RT processivity by PCR indicative for proviral
      DNA synthesis demonstrated that anti-HIV activity has not been linked to early
      stages of viral replication. No effect on late steps of viral replication has
      been found using cells chronically producing HIV-1(LAI) virus. La(W) demonstrated
      anti-HIV activity (IC50=21.4 muM) close to maximal nontoxic concentration. Nd(W),
      Ce(1), and Nd(1) demonstrated limited anti-HIV potency, so none of the complexes
      seems appropriate to be used in clinic. Further targeting of HIV-1 inhibition by
      La(W) is under progress.

PMID- 17497017
TI  - Lanthanide(III) and Yttrium(III) Complexes of Benzimidazole-2-Acetic Acid:
      Synthesis, Characterisation and Effect of La(III) Complex on Germination of
      Wheat.
AB  - The synthesis and characterisation of lanthanide(III) and yttrium(III) nitrate
      complexes of benzimidazole-2-acetic acid (HBIA) are reported. The complexes have
      been characterised by elemental analysis, molar conductance, magnetic studies,
      IR, (1)H NMR, UV-visible, EPR, and TG/DTA studies. They have the stoichiometry
      [Ln(3)(BIA)(2)(NO(3))(7)(H(2)O)(4)] . 3H(2)O where Ln=La(III), Pr(III), Nd(II),
      Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), and Y(III). The effect of La(III)
      complex on germination, coleoptile, and root length of two local varieties of
      wheat DWR-195 and GW-349 for different treatment periods has been investigated.
      The complex was found to exhibit enhanced activity, compared to HBIA or metal
      salt alone at lower treatment periods.

PMID- 17497018
TI  - Proposal for sets of se NMR chemical shifts in planar and perpendicular
      orientations of aryl group and the applications.
AB  - The orientational effect of p-YC(6)H(4) (Ar) on delta(Se) is elucidated for
      ArSeR, based on experimental and theoretical investigations. Sets of delta(Se)
      are proposed for pl and pd employing 9-(arylselanyl)anthracenes (1) and 1
      (arylselanyl)anthraquinones (2), respectively, where Se-C(R) in ArSeR is on the
      Ar plane in pl and perpendicular to the plane in pd. Absolute magnetic shielding
      tensors of Se (sigma(Se)) are calculated for ArSeR (R = H, Me, and Ph), assuming
      pl and pd, with the DFT-GIAO method. Observed characters are well reproduced by
      the total shielding tensors (sigma(t)(Se)). The paramagnetic terms (sigma(P)(Se))
      are governed by sigma(P)(Se)(xx) + sigma(P)(Se)(yy), where the direction of
      n(P)(Se) is set to the z-axis. The mechanisms of the orientational effect are
      established both for pl and pd. Sets of delta(Se: 1) and delta(Se: 2) act as the
      standards for pl and pd, respectively, when delta(Se) of ArSeR are analyzed based
      on the orientational effect.

PMID- 17497019
TI  - Synthesis, Superoxide Dismutase Mimetic and Anticancer Activities of Metal
      Complexes of 2,2-Dimethylpentanedioic Acid(2dmepdaH(2)) and 3,3
      Dimethylpentanedioic acid(3dmepdaH(2)): X-Ray Crystal Structures of
      [Cu(3dmepda)(bipy)](2). 6H(2)O and [Cu(2dmepda)(bipy)(EtOH)](2). 4EtOH (bipy =
      2,2'Bipyridine).
AB  - 2,2-dimethylpentanedioic acid (2dmepdaH(2)) and 3,3-dimethylpentanedioic acid
      (3dmepdaH(2)) reacted with copper(II) acetate to give [Cu(2dmepda)(H(2)O)(3)](2)
      (1) and [Cu(3dmepda)(H(2)O)(3)](2) (2). Reaction of (1) and (2) with 1,10
      phenanthroline and 2,2'-bipyridine yielded [Cu(2dmepda)(phen)(H(2)O)](2)0.5phen
      (3), [Cu(2dmepda)(bipy)(H(2)O)](2) (4), [Cu(2dmepda)(bipy)(EtOH)](2). 2EtOH (4A),
      [Cu(3dmepda)(phen)(H(2)O)](2) (5), and [Cu(3dmepda)(bipy)(H(2)O)](2). (6). The
      structures of (4A) and (6) each consists of a
      [Cu(bipy)(dicarboxylate)(solvent)](2) dimer. The superoxide dismutase (SOD)
      mimetic activity of the novel copper complexes and their manganese analogues was
      investigated. The dimethyl sulphoxide(DMSO) soluble complexes (1)-(4) and (6)
      were assessed for their cancer chemotherapeutic potential towards hepatocellular
      carcinoma and kidney adenocarcinoma cell lines. The 1,10-phenanthroline
      containing complex [Cu(2dmepda)(phen)(H(2)O)](2)0.5phen (3) was the most potent
      with activity that compares well to that of cisplatin.

PMID- 17497020
TI  - Metal-Based Antibacterial and Antifungal Agents: Synthesis, Characterization, and
      In Vitro Biological Evaluation of Co(II), Cu(II), Ni(II), and Zn(II) Complexes
      With Amino Acid-Derived Compounds.
AB  - A series of antibacterial and antifungal amino acid-derived compounds and their
      cobalt(II), copper(II), nickel(II), and zinc(II) metal complexes have been
      synthesized and characterized by their elemental analyses, molar conductances,
      magnetic moments, and IR, and electronic spectral measurements. Ligands (L(1))
      (L(5)) were derived by condensation of beta-diketones with glycine,
      phenylalanine, valine, and histidine and act as bidentate towards metal ions
      (cobalt, copper, nickel, and zinc) via the azomethine-N and deprotonated-O of the
      respective amino acid. The stoichiometric reaction between the metal(II) ion and
      synthesized ligands in molar ratio of M : L (1 : 1) resulted in the formation of
      the metal complexes of type [M(L)(H(2)O)(4)]Cl (where M = Co(II), Cu(II), and
      Zn(II)) and of M : L (1 : 2) of type [M(L)(2)(H(2)O)(2)] (where M = Co(II),
      Cu(II), Ni(II), and Zn(II)). The magnetic moment data suggested for the complexes
      to have an octahedral geometry around the central metal atom. The electronic
      spectral data also supported the same octahedral geometry of the complexes.
      Elemental analyses and NMR spectral data of the ligands and their metal(II)
      complexes agree with their proposed structures. The synthesized ligands, along
      with their metal(II) complexes, were screened for their in vitro antibacterial
      activity against four Gram-negative (Escherichia coli, Shigella flexeneri,
      Pseudomonas aeruginosa, and Salmonella typhi) and two Gram-positive (Bacillus
      subtilis and Staphylococcus aureus) bacterial strains and for in vitro antifungal
      activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus,
      Microsporum canis, Fusarium solani, and Candida glaberata. The results of these
      studies show the metal(II) complexes to be more antibacterial/antifungal against
      one or more species as compared to the uncomplexed ligands. The brine shrimp
      bioassay was also carried out to study their in vitro cytotoxic properties. Five
      compounds, (3), (7), (10), (11), and (22), displayed potent cytotoxic activity as
      LD(50) = 8.974 x 10(-4), 7.022 x 10(-4), 8.839 x 10(-4), 7.133 x 10(-4), and
      9.725 x 10(-4) M/mL, respectively, against Artemia salina.

PMID- 17497021
TI  - Design and synthesis of redox-switched lariat ethers and their application for
      transport of alkali and alkaline-Earth metal cations across supported liquid
      membrane.
AB  - A new class of redox-switched anthraquinone derived lariat ethers 1-(1
      anthraquinonyloxy) 3, 6, 9 trioxaundecane 11-ol (M(1)), 1-(1-anthraquinonyloxy)
      3, 6 dioxaoctane 9-ol (M(2)), 1-(1-anthraquinonyloxy) 3 oxapentane 5-ol (M(3)), 1
      (1-anthraquinonyloxy) 3 oxapentane 5-butane (M(4)), 1-(1-anthraquinonyloxy) 3, 6
      dioxaoctane 9-methane (M(5)) and 1-(1-anthraquinonyloxy) 3 oxapentane 5-methane
      (M(6)) have been synthesized and characterized by spectral analysis. These
      ionophores were used in liquid membrane carrier facilitated transport of main
      group metal cations across supported liquid membrane (SLM). Cellulose nitrate
      membrane was used as membrane support. Effect of various parameters such as
      variation in concentration of metal as well as ionophore, effect of chain length
      and end group of ionophore have been studied. The sequence of metal ions
      transported by ionophore M(1) is Na(+) > Li(+) > K(+) > Ca(2+) > Mg(2+) and the
      order of metal ions transported by ionophores (M(2)-M(6)) is Li(+) > Na(+) > K(+)
      > Ca(2+) > Mg(2+). Ionophore M(1) is selective for Na(+), Li(+), and K(+) and
      ionophores (M(2)-M(6)) are selective for Li(+) and Na(+).

PMID- 17497022
TI  - Therapeutic potential of retinoid x receptor modulators for the treatment of the
      metabolic syndrome.
AB  - The increasing prevalence of obesity is a fundamental contributor to the growing
      prevalence of the metabolic syndrome. Rexinoids, a class of compounds that
      selectively bind and activate RXR, are being studied as a potential option for
      the treatment of metabolic syndrome. These compounds have glucose-lowering,
      insulin-sensitizing, and antiobesity effects in animal models of insulin
      resistance and type 2 diabetes. However, undesirable side effects such as
      hypertriglyceridemia and suppression of the thyroid hormone axis also occur. This
      review examines and compares the effects of four RXR-selective ligands: LGD1069,
      LG100268, AGN194204, and LG101506, a selective RXR modulator. Similar to
      selective modulators of other nuclear receptors such as the estrogen receptor
      (SERMs), LG101506 binding to RXR selectively maintains the desirable
      characteristic effects of rexinoids while minimizing the undesirable effects.
      These recent findings suggest that, with continued research efforts, RXR-specific
      ligands with improved pharmacological profiles may eventually be available as
      additional treatment options for the current epidemic of obesity, insulin
      resistance, type 2 diabetes, and all of the associated metabolic sequelae.

PMID- 17497023
TI  - Distinction between pore assembly by staphylococcal alpha-toxin versus
      leukotoxins.
AB  - The staphylococcal bipartite leukotoxins and the homoheptameric alpha-toxin
      belong to the same family of beta-barrel pore-forming toxins despite slight
      differences. In the alpha-toxin pore, the N-terminal extremity of each protomer
      interacts as a deployed latch with two consecutive protomers in the vicinity of
      the pore lumen. N-terminal extremities of leukotoxins as seen in their three
      dimensional structures are heterogeneous in length and take part in the beta
      sandwich core of soluble monomers. Hence, the interaction of these N-terminal
      extremities within structures of adjacent monomers is questionable. We show here
      that modifications of their N-termini by two different processes, using fusion
      with glutathione S-transferase (GST) and bridging of the N-terminal extremity to
      the adjacent beta-sheet via disulphide bridges, are not deleterious for
      biological activity. Therefore, bipartite leukotoxins do not need a large
      extension of their N-terminal extremities to form functional pores, thus
      illustrating a microheterogeneity of the structural organizations between
      bipartite leukotoxins and alpha-toxin.

PMID- 17497024
TI  - Expression by streptomyces lividans of the rat alpha integrin CD11b A-domain as a
      secreted and soluble recombinant protein.
AB  - We already reported the use of a long synthetic signal peptide (LSSP) to secrete
      the Streptomyces sp. TO1 amylase by Streptomyces lividans strain. We herein
      report the expression and secretion of the rat CD11b A-domain using the same LSSP
      and S. lividans as host strain. We have used the Escherichia coli/Streptomyces
      shuttle vector pIJ699 for the cloning of the A-domain DNA sequence downstream of
      LSSP and under the control of the constitutive ermE-up promoter of Streptomyces
      erythraeus. Using this construct and S. lividans as a host strain, we achieved
      the expression of 8 mg/L of soluble secreted recombinant form of the A-domain of
      the rat leukocyte beta2 integrin CD11/CD18 alpha M subunit (CD11b). This secreted
      recombinant CD11b A-domain reacted with a function blocking antibody showing that
      this protein is properly folded and probably functional. These data support the
      capability of Streptomyces to produce heterologous recombinant proteins as
      soluble secreted form using the "LSSP" synthetic signal peptide.

PMID- 17497025
TI  - Impact of lactic Acid bacteria on dendritic cells from allergic patients in an
      experimental model of intestinal epithelium.
AB  - Lactic acid bacteria (LAB) are Gram positive nonpathogenic commensal organisms
      present in human gastrointestinal tract. In vivo, LAB are separated from antigen
      presenting cells such as dendritic cells (DC) by the intestinal epithelial
      barrier. In this study, the impact of one LAB strain (Lactobacillus casei
      ATCC393) on human monocyte-derived DC from allergic and healthy donors was
      assessed by using a polarized epithelium model. Confocal and flow cytometer
      analyses showed that immature DC efficiently captured FITC-labelled L. casei
      through the epithelial layer. After interaction with L. casei, DC acquired a
      partial maturation status (i.e., CD86 and CD54 increase) and increased their
      interleukin (IL)-10 and IL-12 production. Interestingly, after activation by L.
      casei in the presence of experimental epithelium, DC from allergic patients
      instructed autologous naive CD4(+) T cells to produce more interferon-gamma than
      without the epithelium. Thus by modulating human DC reactivity, LAB and
      intestinal epithelium might modify T cell immune response and regulate the
      development of allergic reaction.

PMID- 17497026
TI  - Thermolabile methylenetetrahydrofolate reductase C677T polymorphism and
      homocysteine are risk factors for coronary artery disease in Moroccan population.
AB  - Increased plasma total homocysteine (tHcy) levels have been shown to be a risk
      factor for coronary artery disease (CAD). The common methylenetetrahydrofolate
      reductase C677T (MTHFR C677T) polymorphism has been reported to be a strong
      predictor of mild hyperhomocysteinaemia (HHcy). We assessed whether this mutation
      was associated with increased risk of CAD and plasma levels of tHcy. We also
      evaluated interactions between this polymorphism, mild elevated tHcy levels and
      conventional risk factors of CAD. Method. Using PCR-RFLP analysis, we studied the
      frequency of the C677T genotypes and its effect on CAD and on tHcy concentrations
      in 400 subjects without and with CAD angiographically confirmed. There were 210
      subjects with CAD and 190 subjects without CAD. Results. The frequencies of the
      C677T genotypes were 53% (59.5% in controls versus 48.1% in cases), 34.8% (32.1
      in controls versus 37.1 in cases), and 11.8% (8.4% in controls versus 14.8% in
      cases), respectively, for 677CC, 677CT, and 677TT. The genotype frequencies were
      significantly different between case and control groups (P < .05). The 677T
      allele enhances the risk of CAD associated to HHcy (P < .01). In multivariate
      analysis models, MTHFR C677T polymorphism effect on CAD was masked by other risk
      factors. HHcy was only and independently influenced by MTHFR polymorphism and
      smoking habits, and it is a strong predictor of CAD independently of conventional
      risk factors. Conclusion. Our data suggest that HHcy is strongly and
      independently associated to CAD risk increase; and MTHFR C677T polymorphism and
      smoking habits were the main predictors of tHcy levels. The CAD risk increase is
      mainly associated with mild HHcy in 677TT, whereas in 677CT and 677CC it is
      mainly associated with the conventional risk factors.

PMID- 17497027
TI  - Insights to clinical use of serial determination in titers of cyclic
      citrullinated peptide autoantibodies.
AB  - Anti-cyclic citrullinated peptide (CCP) antibody is a useful marker for the
      diagnosis and prognosis of rheumatoid arthritis (RA). Recently, clinical
      significance of follow-up in anti-CCP antibody titer has been pointed out. Thus,
      we investigated the serial determination in anti-CCP antibodies titer in RA
      patients. Six patients with RA, who were followed up for longer than 5 years,
      were assessed in anti-CCP antibodies and radiographs (Larsen score). Anti-CCP
      antibodies in frozen sera were measured using ELISA. As a result, 6 patients with
      RA were divided into two groups: one possessed high titers without variation, and
      the other was without high titers. Joint damage progressed during observation in
      2 out of 3 patients with high anti-CCP titers in a retrospective assessment. In
      contrast, the RA patient, whose anti-CCP titer decreases although it had been
      high titer at baseline, did not show increase in the Larsen score. These findings
      suggest that it might be necessary to analyze changes in anti-CCP to predict the
      prognosis of joint destruction.

PMID- 17497028
TI  - Association of GST genes polymorphisms with asthma in Tunisian children.
AB  - BACKGROUND: A positive association between genetic polymorphism and asthma may
      not be extrapolated from one ethnic group to another based on intra- and
      interethnic allelic and genotype frequencies differences. OBJECTIVE: We assessed
      whether polymorphisms of GST genes (GSTM1, GSTT1, and GSTP1) are associated with
      asthma and atopy among Tunisian children. METHODS: 112 unrelated healthy
      individuals and 105 asthmatic (73 atopic and 32 nonatopic) children were studied.
      Genotyping the polymorphisms in the GSTT1 and GSTM1 genes was performed using the
      multiplex PCR. The GSTP1 ILe105Val polymorphism was determined using PCR-RFLP.
      RESULTS: GSTM1 null genotype was significantly associated with the increased risk
      of asthma (P = .002). Asthmatic children had a higher prevalence of the
      GSTP1Ile105 allele than the control group (43.8% and 33.5%, respectively; P =
      .002). Also, the presence of the GSTP1 homozygote Val/Val was less common in
      subjects with asthma than in control group. We have found that GSTT1 null
      genotype (GSTT1 *0/*0) was significantly associated with atopy (P = .008).
      CONCLUSION: Polymorphisms within genes of the GST superfamily were associated
      with risk of asthma and atopy in Tunisia.

PMID- 17497029
TI  - Th1/Th2 cytokine ratio in tissue transudates from patients with oral lichen
      planus.
AB  - OBJECTIVE: The characteristics of oral lichen planus (OLP) provoke investigators
      to explore possible biomarkers by which to monitor disease activity and
      therapeutic efficacy. Oral fluids may provide an accessible medium for analysis
      of such biomarkers. Previous studies have shown that activation of nuclear factor
      kappa B (NF-kappa B) plays an important role in the pathogenesis of oral lichen
      planus (OLP), which is a chronic inflammatory disorder mediated by T cells. Prior
      to the present investigation, reports of the levels of NF-kappa B and its
      dependent cytokines in oral fluids have not been forthcoming. The purpose of this
      study was to detect the level of NF-kappa B dependent cytokines, TNF-alpha, IL-1
      alpha, IL-6, and IL-8 in tissue transudates directly from lesions of OLP, and
      explore the feasibility of the data for clinical application. STUDY DESIGN:
      Thirteen definitively diagnosed OLP subjects were enrolled in the study as were
      13 age-sex matched controls. In each subject, lesion tissue transudates (TTs)
      were collected by a novel collection technique with a filter paper. The level of
      cytokines, TNF-alpha, IL-1-alpha, IL-6, and IL-8 in three types of oral fluids
      were determined by ELISA. RESULTS: In the tissue transudate(TT), there were
      significantly higher level of cytokines TNF-alpha, IL-1-alpha, IL-6, and IL-8
      detected in OLP patients than in controls: (TT: 40.0 +/- 9.8 versus 4.5 +/- 0.7,
      710 +/- 114 versus 305 +/- 78, 150 +/- 25 versus 1.7 +/- 0.5, 2800 +/- 260 versus
      1450 +/- 130, P < .0001; unit: pg/mL). CONCLUSIONS: These results indicate that
      NF-kappa B dependent inflammatory cytokines may be detected at increased levels
      in oral lesion tissue transudates which may have diagnostic and prognostic
      potentials for monitoring disease activity and making therapeutic decisions in
      patients with OLP.

PMID- 17497030
TI  - Tumor necrosis factor-alpha and interleukin 6 in human periapical lesions.
AB  - AIM: The aim of this study was to evaluate the presence of the cytokines tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in human periapical
      lesions. SUBJECTS AND METHODS: Samples were obtained from three groups of teeth:
      symptomatic teeth, asymptomatic lesions, and uninflamed periradicular tissues as
      a control. RESULTS: TNF-alpha levels were significantly increased in symptomatic
      lesions compared to control. Group with asymptomatic lesions had significantly
      higher concentrations compared to control. There were no significant differences
      in TNF-alpha levels between symptomatic and asymptomatic lesions. In group with
      symptomatic lesions, IL-6 levels were significantly higher than in group with
      asymptomatic lesions. The IL-6 levels in symptomatic group also showed
      significantly higher concentration in comparison with control group. In
      asymptomatic group, the IL-6 level had significantly higher concentrations
      compared to control. CONCLUSION: These results indicate that symptomatic lesions
      represent an immunologically active stage of disease, and asymptomatic lesions
      are the point from which the process advances toward healing.

PMID- 17497031
TI  - Insulin-like growth factor (IGF)-I and insulin in normal and growth-restricted
      mother/infant pairs.
AB  - Insulin-like growth factor (IGF)-I and insulin are essential for fetal growth. We
      investigated perinatal changes of both factors in 40 mothers and their 20
      appropriate-for-gestational-age (AGA) and 20 intrauterine-growth-restricted
      (IUGR) fetuses and neonates on day 1 (N1) and day 4 (N4) postpartum. Fetal and
      N1, but not N4, IGF-I levels were increased in AGA (P < .001 and P = .037,
      resp.). N1 insulin levels were lower in IUGR (P = .048). Maternal, fetal, and N1
      IGF-I, and fetal insulin levels positively correlated with customized centiles (r
      = .374, P = .035, r = .608, P < .001, r = .485, P = .006, and r = .654, P = .021,
      resp.). Female infants presented elevated fetal and N4 IGF-I levels (P = .023 and
      P = .016, resp.). Positive correlations of maternal, fetal, and neonatal IGF-I
      levels, and fetal insulin levels with customized centiles underline implication
      of both hormones in fetal growth. IUGR infants present gradually increasing IGF-I
      levels. Higher IGF-I levels are documented in females.

PMID- 17497033
TI  - Leptin levels in various manifestations of pulmonary tuberculosis.
AB  - BACKGROUND: Proinflammatory cytokines are prime candidates as causative agents of
      the metabolic changes that eventually result in tuberculosis-associated weight
      loss. Microbial products and cytokines such as TNF and IL-1 increase leptin
      expression dose dependently in adipose tissue. Leptin plays an important role in
      cellular immunity. OBJECTIVES: In this study, we investigated serum leptin and
      TNF-alpha levels before and after antituberculosis therapy in patients with
      active pulmonary tuberculosis (TB). METHODS: Twenty five in patients with active
      pulmonary TB and 18 healthy controls participated in the study. Leptin and TNF
      alpha levels were measured before treatment and six months after the treatment
      and they were compared with the control group. Body mass index (BMI) and chest X
      rays before and after the treatment were also evaluated. RESULTS: The leptin
      levels before and after the treatment were 1.66+/-1.68 ng/mL and 3.26+/-3.81
      ng/mL, respectively. The leptin levels of tuberculous patients were significant
      than in healthy patients (P < .05). The BMI was 19.36+/-2.55 kg/m2 before the
      treatment and 22.87+/-3.13 kg/m2 after the treatment. The TNF-alpha level was
      23.19+/-12.78 pg/mL before the treatment and 15.95+/-6.58 pg/mL after the
      treatment. There was no correlation between leptin and TNF-alpha levels. Leptin
      levels were low in patients who had sequela lesion on chest radiographs.
      CONCLUSION: Leptin levels are suppressed in tuberculous patients and low leptin
      levels may contribute to increased susceptibility to infection and recovery with
      sequela lesions.

PMID- 17497032
TI  - Calotropis procera latex extract affords protection against inflammation and
      oxidative stress in Freund's complete adjuvant-induced monoarthritis in rats.
AB  - In view of the well-established anti-inflammatory properties of latex of
      Calotropis procera (DL), the present study was carried out to evaluate the
      protective effect of its methanol extract (MeDL) against inflammation and
      oxidative stress in monoarthritis induced by Freund's complete adjuvant (FCA) in
      rats. Intra-articular injection of FCA produced inflammation of the joint with a
      peak effect occurring on day 4 where a maximum increase in the levels of
      myeloperoxidase and inflammatory mediators like PGE2, TNF-alpha, and nitric oxide
      was observed. This was associated with oxidative stress with a marked reduction
      in the levels of glutathione, catalase, superoxide dismutase and glutathione
      peroxidase and an increase in the lipid peroxidation as indicated by the higher
      levels of thiobarbituric acid reactive substances (TBARSs). Subsequently on day
      28 the histological analysis of the joint also revealed arthritic changes. Daily
      treatment of rats with MeDL (50 and 500 mg/kg) and standard anti-inflammatory
      drug rofecoxib (20 and 100 mg/kg), produced a significant attenuation in the
      inflammatory response and ameliorated the arthritic changes in the joint. The
      protection afforded by MeDL and rofecoxib was more pronounced than that of
      phenylbutazone and was associated with normalization of the levels of
      inflammatory mediators and biochemical parameters of oxidative stress. However,
      the overall protection afforded by rofecoxib was better than that of MeDL.

PMID- 17497034
TI  - No correlation exists between disease activity and the expression of killer-cell
      immunoglobulin-like receptors in patients with rheumatoid arthritis.
AB  - OBJECTIVE: The genes for killer-cell immunoglobulin-like receptors (KIRs) have
      been cloned and their functions and expression in patients with rheumatoid
      arthritis (RA) have been partially clarified. However, the correlation between
      their expression and disease activity has not been analyzed in patients with RA.
      Thus, we measured KIR expression on lymphocytes in patients with RA, and assessed
      the correlation between KIR expression and disease activity. PATIENTS AND
      METHODS: In the cross-sectional study, 15 patients (9 females and 6 males) who
      fulfilled the diagnostic criteria for RA were assessed. In the longitudinal
      study, patients who were followed-up for 3 months were assessed. CD158a/b
      expression on peripheral blood mononuclear cells (PBMC) of RA patients was
      analyzed using flow cytometry. RESULTS: No significant correlation between KIR
      expression and CRP, ESR, or IgM-RF was observed. There was no remarkable change
      in the expression of KIRs between the baseline and after 3 months. Additionally,
      in the 5 patients whose expression of KIRs particularly changed, the time-related
      changes in the expression of KIRs were independent from those of inflammation
      parameters and IgM-RF. CONCLUSION: There was no correlation between KIR
      expression and disease activity; therefore, the clinical use of KIR expression
      should be limited, while unnatural KIR expression may be involved in the
      pathogenesis of RA, but not a recruitment of chronic inflammation to induce joint
      damage.

PMID- 17497035
TI  - Plasma levels of tumor necrosis factor-alpha and interleukin-6 in obsessive
      compulsive disorder.
AB  - AIM: Recent research implicated place of an immune mechanism in the
      pathophysiology of obsessive-compulsive disorder (OCD). Despite increasing
      evidence involvement of cytokine release in OCD, results of the studies are
      inconsistent. The aim of this study was to evaluate the plasma levels of the
      cytokines; tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in
      OCD patients. METHODS: Plasma concentrations of TNF-alpha and IL-6 were measured
      in 31 drug-free outpatients with OCD, and 31-year age and sex-matched healthy
      controls. TNF-alpha and IL-6 concentrations in blood were determined by enzyme
      linked immunosorbent assay (ELISA). RESULTS: Both TNF-alpha and IL-6 levels
      showed statistically significant increases in OCD patients compared to controls
      (P < .000, P < .001, resp.). In addition, the age of onset was negatively
      correlated with TNF-alpha level (r = -.402, P = .025) and duration of illness was
      weakly correlated with IL-6 levels (r: .357; P: .048) in patients group.
      CONCLUSION: OCD patients showed increases in TNF-alpha and IL-6 levels compared
      to the healthy controls. This study provides evidence for alterations in the
      proinflammatory cytokines which suggest the involvement of the immune system in
      the pathophysiology of OCD.

PMID- 17497036
TI  - Antioxidant mechanism is involved in the gastroprotective effects of ozonized
      sunflower oil in ethanol-induced ulcers in rats.
AB  - This research was performed in order to determine the potential protective
      effects of ozonized sunflower oil (OSO) in the injury of rat gastric mucosa
      induced by absolute ethanol and as well as to elucidate the role of reactive
      oxygen species (ROS), lipid peroxidation, and some important constituents of
      antioxidant defense such as superoxide dismutase (SOD), glutathione peroxidase
      (GSH-Px), and catalase (CAT) in these effects. OSO was administered to rats
      intragastrically by a cannula and it was applied during four days to animals. The
      doses of OSO administered daily to each group of rats were 4, 12, and 24 mg/kg,
      respectively, and one hour after the last treatment, absolute ethanol (1 mL/200
      mg body weight) was administered. Our results showed that gastric ulcer index was
      significantly reduced in rats pretreated with OSO as compared with ethanol
      treated controls. However, in rats pretreated with OSO, no significant reduction
      of TBARS content in gastric mucosa was found as compared to those rats treated
      with ethanol alone. In contrast, SOD and GSH-Px activities were significantly
      increased in gastric mucosa of OSO-pretreated rats with respect to those treated
      with ethanol alone. In summary, our results demonstrate that OSO pretreatment
      exerts protective effects in ethanol-induced gastric ulcers in rats. Furthermore,
      these results provide evidence that these protective effects of OSO are mediated
      at least partially by stimulation of some important antioxidant enzymes such as
      SOD and GSH-Px, which are scavengers of ROS and therefore prevent gastric injury
      induced by them.

PMID- 17497037
TI  - Angiogenic factor expression in hepatic cirrhosis.
AB  - The pathogenesis of fibrosis in hepatic cirrhosis remains obscure. This study
      examines the eventual role of angiogenic factors in the fibrotic process. A
      series of 55 cirrhotic livers was studied for the proliferation state of
      fibroblasts, and the expression of vascular endothelial growth factor (VEGF),
      thymidine phosphorylase (TP) and the basic and acidic fibroblast growth factor
      (bFGF, aFGF) in both fibroblasts and hepatic cells. The angiogenic and/or
      fibrogenic factors VEGF, TP, bFGF, and aFGF were clearly expressed in
      regenerative hepatocytes, but not in fibroblasts of diffuse hepatic fibrosis. The
      immunohistochemical findings suggest that angiogenic factors and factors
      promoting oxidative stress (i.e., TP) produced by hepatocytes may contribute to
      the development of fibrous bands in hepatic cirrhosis.

PMID- 17497038
TI  - Evaluation of C-reactive protein, endothelin-1, adhesion molecule(s), and lipids
      as inflammatory markers in type 2 diabetes mellitus patients.
AB  - This study compared lipids, the product of lipid peroxidation malondialdehyde
      (MDA), the acute phase reactant high-sensitive C-reactive protein (hsCRP),
      endothelin-1 (ET-1), P-selectin, intercellular adhesion molecule-1 (ICAM-1), and
      vascular cell adhesion molecule-1 (VCAM-1) between healthy controls, subjects
      with ischemic heart disease (IHD) and type 2 diabetes mellitus (DM) subjects who
      did not perform coronary artery bypass graft (CABG) surgery as well as type 2 DM
      subjects who performed CABG. HbA1c, lipids, MDA, hsCRP, ET-1, P-selectin, ICAM-1,
      and VCAM-1 levels were significantly higher in the diabetic groups than in either
      healthy controls or IHD subjects. In the diabetic groups, there was a negative
      association among hsCRP and HDL-C. ET-1, ICAM-1 levels, and TAG were positively
      correlated, as do the association between P-selectin, VCAM-1, and HbA1c%. Also a
      positive relation was found among hsCRP levels and ICAM-1, as well as MDA and ET
      1. P-selectin and ICAM-1 were significantly positively correlated. This study
      indicates that increased level of oxidative stress marker, proinflammatory
      markers, and their downstream effectors adhesion molecules occur in type 2 DM.

PMID- 17497039
TI  - Accumulation of oxidized low-density lipoprotein in psoriatic skin and changes of
      plasma lipid levels in psoriatic patients.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by an
      accelerated turnover of epidermal cells and an incomplete differentiation in
      epidermis with lesion. However, the exact etiology of psoriasis is unknown.
      Abnormalities in essential fatty acid metabolism, free radical generation, lipid
      peroxidation, and release of lymphokines have been proposed. OBJECTIVE: Our
      purpose was to evaluate the plasma lipids and oxidized low-density lipoprotein
      accumulation in psoriatic skin lesion in order to ascertain the possible
      participation of oxidative stress and oxidative modification of lipids in
      pathogenesis of psoriasis. METHODS: The study group included 84 patients with
      psoriasis, and 40 sex- and age-matched healthy volunteers. Blood lipid profile
      was determined. Psoriatic and nonlesional skin samples of psoriatic patients were
      evaluated for the presence of oxidized low-density lipoprotein by using an immune
      fluorescent staining method. RESULTS: The mean levels of lipids (total
      cholesterol, triglyceride, and LDL cholesterol) in patients with psoriasis were
      found to be significantly higher than those of healthy subjects. Psoriatic skins
      were shown positive oxidized low-density lipoprotein staining. There was no
      staining in nonlesional skin samples of the same individuals. CONCLUSION: Lipid
      peroxidation mediated by free radicals is believed to be one of the important
      causes of cell membrane destruction and cell damage. This study shows for the
      first time the accumulation of oxidized low-density lipoprotein in psoriatic skin
      lesion. We believe that accumulation of ox-LDL in psoriatic skin may have an
      important role in the immune-inflammatory events that result in progressive skin
      damage.

PMID- 17497040
TI  - The level of hs-CRP in coronary artery ectasia and its response to statin and
      angiotensin-converting enzyme inhibitor treatment.
AB  - BACKGROUND/AIM: Coronary artery ectasia (CAE) was thought of as a variant of
      atherosclerosis. C-reactive protein (CRP) which is among the most sensitive
      markers of systemic inflammation, and elevation of systemic and local levels of
      this inflammatory marker which has been associated with an increased risk for
      cardiovascular disease in the obstructive coronary artery disease (O-CAD) are
      well known, but little was known in CAE. The anti-inflammatory effects of statins
      and the effect of angiotensin-converting enzyme (ACE) inhibitors on endothelial
      dysfunction are well established in atherosclerosis. The aim of the present study
      was to investigate CRP level and its response to statin and ACE inhibitor
      treatment in CAE. MATERIALS AND METHOD: We measured serum hs-CRP level in 40 CAE
      (26 males, mean age: 56.32 +/- 9 years) and 41 O-CAD (34 males, mean age: 57.19
      +/- 10 years) patients referred for elective coronary angiography at baseline and
      after 3-month statin and ACE inhibitor treatment. RESULTS: Plasma hs-CRP levels
      were significantly higher in CAE group than O-CAD group at baseline (2.68 +/- 66
      mg/L versus 1, 64 +/- 64, resp., P < .0001). Plasma hs-CRP levels significantly
      decreased from baseline 3 months later in the CE (from 2.68 +/- 0.66 mg/L to 1.2
      +/- 0.53 mg/L, P < .0001) as well as in the O-CAD group (from 1.64 +/- 0.64 mg/L
      to 1.01 +/- 0.56 mg/L, P < .001). CONCLUSION: We think that hs-CRP measurement
      may be a good prognostic value in CAE patients as in stenotic ones. Further
      placebo-controlled studies are needed to evaluate the clinical significance of
      this decrease in hs-CRP.

PMID- 17497042
TI  - Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous
      leaf extract in experimental animals.
AB  - The cardiovascular effects of Persea americana Mill (Lauraceae) aqueous leaf
      extract (PAE) have been investigated in some experimental animal paradigms. The
      effects of PAE on myocardial contractile performance was evaluated on guinea pig
      isolated atrial muscle strips, while the vasodilatory effects of the plant
      extract were examined on isolated portal veins and thoracic aortic rings of
      healthy normal Wistar rats in vitro. The hypotensive (antihypertensive) effect of
      the plant extract was examined in healthy normotensive and hypertensive Dahl salt
      sensitive rats in vivo. P americana aqueous leaf extract (25-800 mg/ml) produced
      concentration-dependent, significant (p < 0.05-0.001), negative inotropic and
      negative chronotropic effects on guinea pig isolated electrically driven left and
      spontaneously beating right atrial muscle preparations, respectively. Moreover,
      PAE reduced or abolished, in a concentration-dependent manner, the positive
      inotropic and chronotropic responses of guinea pig isolated atrial muscle strips
      induced by noradrenaline (NA, 10(-10)-10(-5) M), and calcium (Ca(2+), 5-40 mM).
      PAE (50-800 mg/ml) also significantly reduced (p < 0.05-0.001) or abolished, in a
      concentration-dependent manner, the rhythmic, spontaneous, myogenic contractions
      of portal veins isolated from healthy normal Wistar rats. Like acetylcholine
      (ACh, 10(-8)-10(-5) M), the plant extract (25- 800 mg/ml) produced concentration
      related relaxations of isolated endothelium-containing thoracic aortic rings pre
      contracted with noradrenaline. The vasorelaxant effects of PAE in the isolated,
      endothelium-intact aortic rings were markedly inhibited or annulled by N(G)-nitro
      L-arginine methyl ester (L-NAME, 10(-5) M), a nitric oxide synthase inhibitor.
      Furthermore, PAE (25-400 mg/kg iv) caused dose-related, transient but significant
      reductions (p < 0.05-0.001) in the systemic arterial blood pressure and heart
      rates of the anaesthetised normotensive and hypertensive rats used. The results
      of this laboratory animal study indicate that PAE caused bradycardia,
      vasorelaxation and hypotension in the mammalian experimental models used. The
      vasorelaxant action of PAE was endothelium dependent, and was, therefore,
      possibly dependent on the synthesis and release of nitric oxide (NO). The
      vasorelaxant effects of PAE appeared to contribute significantly to the
      hypotensive (antihypertensive) effects of the plant extract. However, the
      findings of this study tend to suggest that P americana leaf could be used as a
      natural supplementary remedy in essential hypertension and certain cases of
      cardiac dysfunctions in some rural Africa communities.

PMID- 17497041
TI  - Increased endothelin-1 levels of BAL fluid in patients with Behcet's disease.
AB  - OBJECTIVE AND BACKGROUND: Pulmonary aneurysms and thrombosis constitute a
      significant cause of morbidity and mortality in Behcet's disease (BD). Various
      factors have been studied to explore the pathogenesis of vascular involvement in
      BD. As endothelin (ET) is known for its potent vasoconstrictor and
      proinflammatory properties, we supposed that it is involved during the
      inflammatory process of BD pulmonary vasculitis. METHODS: To investigate the role
      of ET in BD, ET-1 concentrations were measured in bronchoalveolar lavage fluid
      (BALF) of 18 nonsmoking BD patients with pulmonary manifestations and 12 control
      subjects. Immunoreactivity of ET-1 was also evaluated in alveolar macrophages
      (AMs) cytoplasm. RESULTS: ET-1 levels in BD-BALF were significantly higher than
      those of controls. ET-1 levels were correlated with the number of alveolar
      macrophages, but not with BAL-CD4/CD8 ratio. ET-1-immunoreactivity was found
      mainly in AM of BD-BAL. CONCLUSIONS: Increased ET-1 production from AM is
      associated with pulmonary BD manifestations.

PMID- 17497043
TI  - Unexpectedly high prevalence of target-organ damage in newly diagnosed Nigerians
      with hypertension.
AB  - INTRODUCTION: Hypertension remains a formidable cardiovascular problem in the
      entire world. Untreated or poorly controlled hypertension predisposes to target
      organ damage and is often followed by serious cardiovascular events. Knowledge of
      the type and distribution of endorgan damage in newly diagnosed hypertensive
      patients would help to determine the interventions or preventative measures
      needed in such patients. OBJECTIVE: To assess target-organ involvement in newly
      diagnosed, untreated hypertensive patients presenting at the University College
      Hospital, Ibadan, Nigeria. METHODS: Newly diagnosed hypertensive men and women
      were recruited consecutively into the study. Target-organ damage was assessed
      using electroctrocardiography, echocardiography, renal function assessment
      (including tests for albuminuria) and fundoscopy. RESULTS: A total of 68 subjects
      were recruited, but only 54 (79.4%), with a mean age of 59.1 ( +/- 12.4) years,
      completed the study. There were 29 ( +/- 53.7%) men, mean age 63.5 ( +/- 12.6)
      years, and 25 (46.3%) women, mean age 54.1 ( +/- 10.4) years. Fifty per cent of
      the subjects had no symptoms. Some form of albuminuria was found in about 40.7%.
      Seventy-one per cent (71%) had between grade 1 and 2 hypertensive retinopathy.
      Only six (11.1%) had glomerular filtration rate greater than 90 ml/min. Systolic
      function was impaired in three (5.6%) of the subjects. Diastolic dysfunction was
      present in 36 (66.7%) subjects. CONCLUSION: Target-organ damage already exists in
      newly diagnosed hypertensive subjects before presentation. We suggest early
      screening for cardiovascular risk factors and possibly a reduction in the
      criteria for the definition of hypertension in black Africans.

PMID- 17497044
TI  - Pulmonary arterial hypertension after splenectomy for hereditary spherocytosis.
AB  - Hereditary spherocytosis consists of a group of haemolytic anaemias caused by
      defects in the proteins involved in the vertical interactions between the
      membrane skeleton and the lipid bilayer of the red blood cell. Inheritance is
      most commonly autosomal dominant with variable expression. Splenectomy may be
      indicated because of anaemia or for the prevention of gall-stones. We describe a
      patient who presented with symptoms of pulmonary hypertension 32 years after
      splenectomy. Idiopathic pulmonary arterial hypertension (IPAH) and chronic
      thromboembolic pulmonary hypertension (CTEPH) have been associated with
      splenectomy, while chronic haemolysis may result in haemolysis-associated
      pulmonary hypertension. We briefly discuss the current views on the
      pathophysiology, diagnosis and management of this rare condition.

PMID- 17497045
TI  - Beta-blockers in 2007?

PMID- 17497046
TI  - Eprosartan in secondary prevention of stroke: the economic evidence.

PMID- 17497053
TI  - [Protective effects of the growth hormone (GH) on the irradiated spinal cord in
      rats].
AB  - Radiotherapy or irradiation of SNC AVM's or tumors also presents a high risk for
      provoking lesions in adjacent surrounding tissue. The objective of our study is
      to demonstrate radiotherapy induced alterations in a rat spinal cord model and
      evaluate the protective effect of Growth Hormone (GH) on rats exposed to high
      radiotherapy doses. The experimental study employed two groups of Wistar rats:
      Group A (control group):10 rats, which received 30 Gy at the spinal cord . Group
      B: 10 rats, these animals received 30 Gy and dose of 2mg/kg/day GH. Growth
      hormone administration was begun three days before radiotherapy and continued
      until two days after radiotherapy for a total of six days. At 14 days
      postradiotherapy, all the rats were sacrificed and the spinal cord extracted
      immediately. Hematoxyline-eosine histologic studies showed that control animals
      only exposed to radiotherapy had severe alterations with hemorrhage and
      vacuolisation of the entire irradiated segment while these alterations were much
      less severe in the GH-treated group. In conclusion, 30 Gy irradiation produced
      morphological changes including vascular endothelial oedema, necrosis,
      hemorrhage, and inflammatory exudates. A 2 mg/kg/day dose of GH protected the rat
      spinal cord against the noxious effects of the radiotherapy, decreasing the
      clinical, macro and microscopic damage in the treated animals.

PMID- 17497054
TI  - [Neurological sequelae of child abuse. Literature review].
AB  - Child abuse is both socially and medically troublesome and many times produces
      permanent consequences. A review of the literature is done from a neurosurgical
      standpoint, and the lesions produced at the Central Nervous System are evaluated
      in detail, including their physiopathology, neurological sequels and implications
      for rehabilitation treatment and the child's future life.

PMID- 17497055
TI  - [Diagnostic and therapeutic difficulties in neurocysticercosis: presentation of 6
      cases and review of the literature].
AB  - INTRODUCTION: The incidence of neurocysticercosis (NCC) is increasing currently
      in developed countries due to the migration movements from endemic countries. Due
      to NCC polymorphism, treatment would be individualized in each case. Countries
      not used to this disease have to deal with. GOALS: To set up diagnostic and
      therapeutic guidelines in all sorts of NCC and choose the correct treatment would
      be challenging. PATIENTS AND METHODS: To perform a descriptive and retrospective
      analysis of six cases of NCC seen in the Neurosurgery Department of the Hospital
      Clinic de Barcelona from 1992 to 2000 (both included). We have performed a
      revision of the literature about diagnostic and therapeutic methods. DISCUSSION:
      Definitive or probable diagnosis of NCC is based on clinical, imaging,
      immunological, and epidemiological criteria. In patients with inactive disease
      only symptomatic treatment is indicated. In active parenchymal forms there are
      not consensus if antiparasitic treatment is indicated. However, in
      extraparenchymal active disease aggressive treatment with antiparasitic agents
      and steroids is recommended. In cases of intracranial hypertension, neurological
      deficits or hydrocephalus surgery is the treatment of choice.

PMID- 17497056
TI  - Late prevertebral abscess following anterior cervical plating: the missing screw.
AB  - A 51-year-old man underwent a C5-C7 anterior decompression and fusion. Six years
      later the patient complained of dysphagia caused by displacement of the cervical
      plate. One week after the scheduled removal of the implanted material, the
      patient developed a painful cervical swelling and fever. His cervical radiographs
      showed that a screw was missing compared to previous studies. Computerized
      tomography showed a large prevertebral abscess anterior to C4-C7. He underwent
      emergency surgical drainage of the abscess that was followed by total recovery.
      This report is aimed at describing this unusual complication of cervical
      instrumentation and to briefly review its pathogenesis and management options.

PMID- 17497057
TI  - [Chordoid glioma of the III ventricle. Case report and revision of the
      literature].
AB  - Chordoid glioma of the third ventricle is an infrequent brain tumour that was
      described for the first time by Brat et al. in 1998; since then, only 39 cases
      have been reported. We present a new case of chordoid glioma of the third
      ventricle in a 51-year-old-man that was treated with total surgical removal, with
      a good initial postoperative evolution. Sudden death, most likely due to a
      massive pulmonary embolism, occurred in the third postoperative day. We present
      the histological characteristics of the tumour and review the literature
      regarding this entity.

PMID- 17497058
TI  - Ganglioglioma with lytic skull lesions: a case report.
AB  - Gangliogliomas represent only 0.4% of central nervous system neoplasms and 1.3%
      of brain tumors. They are benign neoplasms with low morbidity and mortality and
      the patients usually present with seizures, but there has been no adult
      ganglioglioma with lytic skull lesion. A 49-year-old right handed woman suffering
      from generalized epileptic seizures was admitted to our hospital. She had also
      left hemiparesis with 4/5 motor strength. Magnetic resonance imaging and
      immunohistochemical studies revealed WHO Grade II ganglioglioma. Skull X-ray
      showed the lytic skull lesions. We have to consider gangliogliomas in the
      differential diagnosis of lytic skull lesions.

PMID- 17497059
TI  - Delayed intracerebral hemorrhage after ventriculoperitoneal shunt insertion. Case
      report and literature review.
AB  - We present another case of delayed intracerebral hemorrhage after a
      ventriculoperitoneal (VP) shunting procedure. In this case, a right occipital
      intraparenchymal hematoma and associated intraventricular hemorrhage occurred six
      days after the operation for hydrocephalus secondary to subarachnoid hemorrhage
      in a 64 year old woman. It is a rare complication of VP shunting, with few cases
      reported previously in the literature. The presumed mechanism is the erosion of a
      cerebral blood vessel secondary to a close contact with the ventricular catheter;
      bleeding disorder, vascular malformation, head trauma or brain tumor were
      excluded in this patient.

PMID- 17497060
TI  - [Intraventricular tension pneumocephalus after transsphenoidal surgery: a case
      report and literature review].
AB  - Tension pneumocephalus is a rare complication of transsphenoidal approaches. The
      case of a 37 year old woman with a transsphenoidal resection of a pituitary
      adenoma who presented self-limited rhinoliquorrhea postoperatively is reported.
      Three days later the patient developed progressive decreased consciousness,
      amnesia and headache, showing an intraventricular tension pneumocephalus on CT
      scan. Urgent treatment with bilateral external ventricular drainage and anterior
      nasal tamponade was performed with good clinical outcome. Later transsphenoidal
      sealing of the dural defect was achieved without recurrence. Tension
      pneumocephalus following transsphenoidal surgery usually occurs after the
      presentation of a cerebrospinal fluid leak due to an incomplete sealing of the
      sphenoid sinus. The postoperative insertion of a lumbar drainage seems to be a
      predisposing condition for this complication. The combined approach of tension
      pneumocephalus with external ventricular drainage and repair of the sphenoid
      sinus offers optimal results solving the acute neurological deterioration and
      avoiding recurrence.

PMID- 17497061
TI  - [Spontaneous resolution of a lumbar disc herniation].
AB  - Lumbar disc herniation is a common cause of lower leg radiculopathy and the most
      effective methods of treatment remain in question. Both surgical and nonsurgical
      treatments may provide a successful outcome in appropriately selected patients.
      The spontaneous resolution of herniated lumbar discs is a well-established
      phenomenon. The authors present a case of spontaneous regression of a herniated
      lumbar nucleus pulpous in a patient with radiculopathy.

PMID- 17497062
TI  - [Symptomatic cervical stenosis due to calcification of the ligamentum flavum
      after mild cervical trauma].
AB  - INTRODUCTION: The calcification of ligamentum flavum (CLF) is a rare disease
      mainly affecting middle or advanced aged Japanese women. Several clinical and
      radiological features differentiate CLF from the ossification of the ligamentum
      flavum (OLF). We present a case of symptomatic cervical-dorsal stenosis
      presenting after mild cervical trauma in a patient with a remarkable CLF who
      underwent decompressive laminectomy. The literature regarding CLF is reviewed.
      CASE REPORT: A 65 year-old female suffered mild cervical trauma as a consequence
      of a car accident. A year later she referred progressive cervical and upper
      dorsal pain without any sensory or motor defect. Spinal magnetic resonance images
      showed a well-delineated posterior epidural mass, from C2 to T2, which compressed
      the spinal cord, without signal of myelopathy. She underwent bilateral
      laminectomy of the affected levels but no clear improvement occurred. The
      pathological study of the resected pieces showed a remarkable calcification of
      the ligamentum flavum. DISCUSSION: The CLF is a kind of dystrophic calcification
      of unknown pathogenesis but likely related to the spinal degenerative changes. It
      usually presents in Japanese females. A definite relation between CLF and
      cervical trauma has not been established so far, although the latter may possibly
      trigger the symptoms. Typically, CLF presents in women in the seventh decade,
      affects preferably the cervical region, it shows nodular or diffuse pattern in
      the computerized tomography, it is hypointense in TI and T2-weighted MR sequences
      and exhibits minimum enhancement after gadolinium administration. CLF
      differentiates from OLF easily by demonstrating the presence of mature bone
      formation in the latter. Clinically, CLF may present as radiculopathy or
      myelopathy. The treatment of choice in symptomatic patients is posterior
      decompression. Excellent results after laminectomy are reported. Future similar
      observations will be important from a medical-legal point of view if a relation
      between CLF and cervical trauma is established since CLF may potentially turn
      into a severe condition.

PMID- 17497063
TI  - Patient-selected goals: the fourth dimension in assessment of pelvic floor
      disorders.
AB  - The purpose of the study was to assess the relationship between self-expressed
      urogynecologic goals, symptoms, and treatment choice. Charts of women presenting
      for urogynecology consultation were reviewed. Demographics, diagnoses and
      responses to the pelvic floor distress inventory and medical, social, and
      epidemiologic aspects of aging questionnaires were recorded. Patients listed
      urogynecology goals before consultation. We categorized goals into five
      categories and then compared these categories by symptom type, severity, and
      treatment. Three hundred five women reported 635 goals (median 2, range 1-6). The
      number of goals listed per patient did not differ by age, race, comorbidities, or
      clinical diagnosis (p > 0.05). The most frequent goal category was symptoms
      (67%), followed by information seeking (12%), lifestyle (11%), emotional (4%),
      and "other" (6%). Women selecting non-surgical treatment were more likely to list
      information seeking as primary goal than those who chose surgery (p = 0.009). One
      third of participants expressed a primary non-symptom goal and were more likely
      to seek non-surgical therapy.

PMID- 17497064
TI  - Use of the Amplatzer Vascular Plug as a coil constrainer during endovascular
      occlusion of a dialysis shunt.

PMID- 17497065
TI  - Stenting in acute lower limb arterial occlusions.
AB  - Management of critical limb ischemia of acute onset includes surgical
      embolectomy, bypass grafting, aspiration thrombectomy, thrombolysis, and
      mechanical thrombectomy followed by treatment of the underlying cause. We present
      our experience with the use of stents to treat acute embolic/thrombotic
      occlusions in one iliac and three femoropopliteal arteries. Although this is a
      small case series, excellent immediate and midterm results suggest that stenting
      of acute occlusions of the iliac, superficial femoral, and popliteal arteries is
      a safe and effective treatment option.

PMID- 17497066
TI  - Initial clinical experience using the Amplatzer Vascular Plug.
AB  - BACKGROUND AND PURPOSE: The Amplatzer Vascular Plug (AVP) is a self-expanding
      nitinol wire mesh vascular embolization device derived from the Amplatz septal
      occluder. We assessed the results of vascular embolization obtained using the
      AVP. METHODS: A retrospective review was carried out of 23 consecutive cases of
      vascular embolization using the AVP in a variety of different clinical settings.
      The AVP was chosen to have a diameter approximately 30-50% greater than the
      target vessel. The device was delivered via an appropriately sized guide catheter
      and was released when satisfactorily positioned. Additional embolic agents were
      used in some cases. RESULTS: All target vessels were successfully occluded with
      no device malpositioning or malfunction. In 14 (61%) patients the AVP was the
      sole embolic material. In the remaining patients additional agents were used,
      particularly in preoperative embolization of highly vascular renal tumors. The
      AVP does not cause instantaneous thrombosis and in high-flow situations
      thrombosis typically takes up to 15 min. CONCLUSION: The AVP is a safe, effective
      embolization device that provides a useful adjunct to the therapeutic
      armamentarium. It is particularly suited to the treatment of short high-flow
      vessels where coil migration and catheter dislodgment might occur. In the
      majority of cases no additional embolic agents are necessary but it may take up
      to 15 min for complete thrombosis to occur.

PMID- 17497067
TI  - Embolotherapy of an arterioportal fistula.
AB  - We present a complex case of a splanchnic arterioportal vein fistula in a patient
      who presented with weight loss, abdominal pain, diarrhea, and pancreatitis. We
      report successful use of the Guglielmi Detachable Coil (GDC) and N-butyl
      cyanoacrylate glue for the therapeutic embolization of the fistula between the
      superior mesenteric artery, the common hepatic artery, and the portal vein. On
      the day following the procedure, the patient reported total remission of the
      abdominal pain and diarrhea. These results were maintained at 3 months follow-up.

PMID- 17497068
TI  - Endovascular exclusion of an external carotid artery pseudoaneurysm using a
      covered stent.
AB  - Aneurysmal lesions of the external carotid artery are extremely rare. A case is
      presented of a 3.8 cm right external carotid artery pseudoaneurysm treated by
      transluminal exclusion using an endovascular stent-graft. Following stent-graft
      placement, complete occlusion of the aneurysmal sac and main vessel lumen patency
      was successfully demonstrated. This report demonstrates the technical feasibility
      of utilizing stent-grafts to treat aneurysmal lesions involving the external
      carotid artery.

PMID- 17497069
TI  - CT-guided placement of a drainage catheter within a pelvic abscess using a
      transsacral approach.
AB  - A 66-year-old man underwent CT-guided drainage catheter placement within a pelvic
      abscess with a diameter of 46 mm. We performed the drainage by a transsacral
      approach because it was considered the safest and most feasible approach. An 8G
      bone marrow biopsy needle was used to penetrate the sacrum to create a path for
      subsequent drainage catheter insertion. After withdrawal of the biopsy needle, a
      6 Fr catheter was advanced into the abscess cavity through the path using the
      Seldinger technique. Except for bearable pain, no procedure-related complications
      occurred. Twenty-nine days after the placement, the catheter was withdrawn safely
      and the abscess cavity had shrunk remarkably.

PMID- 17497070
TI  - Endovascular repair of a ruptured mycotic aneurysm of the common iliac artery.
AB  - This report describes the case of a ruptured mycotic aneurysm of the left common
      iliac artery, successfully treated with endovascular stent-grafting. A 64-year
      old woman underwent diagnostic coronary angiography complicated by an infected
      hematoma of the left groin. Seven days later, she developed methicillin-resistant
      Staphylococcus aureus septicemia and CT scan evidence of perivascular
      inflammation around the left common iliac artery. This was followed by rupture of
      a mycotic aneurysm of the left common iliac artery. The lesion was successfully
      treated with a stent-graft and prolonged antibiotic therapy, and the patient
      remains free of infection 10 months later. Accumulating evidence suggests that
      endovascular repair can be used safely for the repair of ruptured infected
      aneurysms.

PMID- 17497071
TI  - Percutaneous radiofrequency ablation and transcatheter arterial chemoembolization
      for hypervascular hepatocellular carcinoma: rate and risk factors for local
      recurrence.
AB  - PURPOSE: To analyze local recurrence-free rates and risk factors for recurrence
      following percutaneous radiofrequency ablation (RFA) or transcatheter arterial
      chemoembolization (TACE) for hypervascular hepatocellular carcinoma (HCC).
      METHODS: One hundred and nine nodules treated by RFA and 173 nodules treated by
      TACE were included. Hypovascular nodules were excluded from this study. Overall
      local recurrence-free rates of each treatment group were calculated using the
      Kaplan-Meier method. The independent risk factors of local recurrence and the
      hazard ratios were analyzed using Cox's proportional-hazards regression model.
      Based on the results of multivariate analyses, we classified HCC nodules into
      four subgroups: central nodules < or =2 cm or >2 cm and peripheral nodules < or
      =2 cm or >2 cm. The local recurrence-free rates of these subgroups for each
      treatment were also calculated. RESULTS: The overall local recurrence-free rate
      was significantly higher in the RFA group than in the TACE group (p = 0.013). The
      24-month local recurrence-free rates in the RFA and TACE groups were 60.0% and
      48.9%, respectively. In the RFA group, the only significant risk factor for
      recurrence was tumor size >2 cm in greatest dimension. In the TACE group, a
      central location was the only significant risk factor for recurrence. In central
      nodules that were < or =2 cm, the local recurrence-free rate was significantly
      higher in the RFA group than in the TACE group (p < 0.001). In the remaining
      three groups, there was no significant difference in local recurrence-free rate
      between the two treatment methods. CONCLUSION: A tumor diameter of >2 cm was the
      only independent risk factor for local recurrence in RFA treatment, and a central
      location was the only independent risk factor in TACE treatment. Central lesions
      measuring < or =2 cm should be treated by RFA.

PMID- 17497072
TI  - Analysis of carbonylated proteins in bronchoalveolar lavage of patients with
      diffuse lung diseases.
AB  - Diffuse lung diseases (DLD) are a heterogeneous group of diseases with different
      etiopathogenesis, clinical course, and prognosis. It has been demonstrated that
      oxidative stress can contribute to the pathogenesis of these diseases. In the
      present study we measured carbonylated protein concentrations in the BAL of
      patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis,
      idiopathic pulmonary fibrosis, and for the first time in patients with chronic
      eosinophilic pneumonia and extrinsic allergic alveolitis. Our aim was to further
      investigate oxidation products in diffuse lung diseases. Oxidatively modified
      protein concentrations were increased in the BAL of patients than in that of
      controls (0.22 nmol/mg protein vs 0.05 nmol/mg protein; p < 0.001) and in each
      group of disease versus controls, suggesting that proteins that have become
      dysfunctional by oxidation could play a role in the pathogenesis of diffuse lung
      diseases. Further studies in a greater number of patients are needed to
      understand the contribution of oxidatively modified proteins to the pathogenesis
      of DLD and, in particular, to the development of extrinsic allergic alveolitis
      where the highest levels of carbonylated proteins were found.

PMID- 17497073
TI  - Dietary flavones suppresses IgE and Th2 cytokines in OVA-immunized BALB/c mice.
AB  - BACKGROUND: The flavonoids are a diverse family of chemicals commonly found in
      fruits and vegetables. Previously, we have shown that the two flavones, chrysin
      and apigenin could suppress the expression of the high affinity IgE receptor
      FcepsilonRI in human basophilic KU812 cells. We also demonstrated that dietary
      apigenin decreased IgE level in C57BL/6N mice sera. AIM OF THE STUDY: To evaluate
      the anti-allergic effect of the two flavones in vivo, we evaluated the effect of
      the two flavones, chrysin and apigenin, on the immune system in BALB/c mice
      sensitized with ovalbumin (OVA). METHODS: Mice were fed experimental diets
      containing either of the flavones for 3 weeks and immunized with OVA. After the
      experimental feeding period, measurement of Igs concentration in the mice sera
      was performed using a sandwich ELISA. Cytokines expression in mice sera was
      assessed using a cytokine array. Furthermore, cytokines mRNA levels in spleen
      lymphocytes from mice sensitized with OVA were measured by RT-PCR. RESULTS: The
      total IgE level in mice fed one of the two flavones were suppressed, whereas
      levels of IgG, IgM, and IgA were not affected. The production of interleukin (IL)
      4, which is known as one of Th2 cytokines and regulates the production of IgE,
      was down-regulated by the chrysin or the apigenin diet. Moreover, OVA-induced
      mRNA expression of Th2 cytokines in spleen lymphocytes from mice sensitized with
      OVA, such as IL-4 and IL-13 were down-regulated by the chrysin or the apigenin
      diet. CONCLUSIONS: The results suggest that the diet containing one of the two
      flavones might suppress the up-regulation of serum IgE induced by OVA
      immunization through the suppression of Th2-type immune response.

PMID- 17497074
TI  - Iodine prophylaxis--the protective factor against stomach cancer in iodine
      deficient areas.
AB  - BACKGROUND: Poland has one of the highest death rates for stomach cancer in
      Europe. Moderate iodine deficiency and in consequence high goitre prevalence led
      to the implementation in 1996 of a very efficient mandatory model of iodine
      prophylaxis, based on household salt iodisation (30 +/- 10 mg KI/1 kg of salt).
      AIM OF THE STUDY: The aim of the study was evaluation of incidence rate of
      stomach cancer and its possible relation to increased iodine consumption in the
      years 1992-2004. METHODS: Iodine supply and effectiveness of iodine prophylaxis
      were evaluated on the basis of comparative analysis of goitre prevalence and
      ioduria in schoolchildren. To allow comparison between time periods with varying
      population age structures, the incidence rates of stomach cancer were
      standardized for age, using the "world standard population". The direct
      standardization method has been applied. For each sex, the time-trend of
      incidence rates was shown in graphs over the years 1991-2004. RESULTS: Evident
      increase in iodine consumption in this period of time was proved by rise in
      percentage of schoolchildren (6-8 years old) with ioduria above 100 microg/l from
      11.4% in 1992-1993 to 52.9.1% in 2003. It was correlated with the decrease in
      goitre prevalence from 18.8% to 3.2% respectively. The 24-h thyroid uptake of
      (131)I in investigated population fell from 45.5% in 1986 to 26.8% in 1998. In
      Krakow the standardized incidence ratio of stomach cancer for men decreased from
      19.1 per 100,000 to 15.7 per 100,000, and for women from 8.3 per 100,000 to 5.9
      per 100,000 in the years 1992-2004. A significant decline of average rate of
      decrease was observed in men and women (2.3% and 4.0% per year respectively).
      CONCLUSION: Observed association between improved iodine supply and decrease of
      incidence of stomach cancer could indicate the protective role against stomach
      cancer of iodine prophylaxis in iodine deficient areas--further studies are
      necessary.

PMID- 17497075
TI  - Colostrum TGF-beta-1 associates with the duration of breast-feeding.
AB  - BACKGROUND: Several stressful environmental factors are associated with short
      term breast-feeding. A high concentration of sodium in colostrum has predicted
      early failure. AIM OF THE STUDY: We studied the association of growth factors in
      colostrum and the length of breast-feeding (BF). METHODS: We measured
      concentrations of TGF-beta1 and -beta2; epidermal growth factor, total protein,
      and sodium and compared their concentrations in colostral samples from mothers
      who either breast-fed their infants exclusively less than 0.5 months (n = 109) or
      longer than 3.5 months (n = 119). RESULTS: In the short BF group more mothers
      smoked and were primiparous more frequently and had less often a university
      education. They also provided the colostral samples significantly later than did
      those with long BF. Geometric mean concentration for TGF-beta1 was 1.9 times as
      high in the samples from short BF mothers as in those with long BF; significant
      difference remained in comparisons of samples taken equally long postpartum.
      Samples from the short BF group showed higher levels for sodium, TGF-beta2 and
      total protein, whereas concentrations of epidermal growth factor were similar
      between groups. CONCLUSIONS: We thus infer that concentrations of factors in
      breast milk with an effect on the development and involution of the mammary
      gland, like TGF-beta1 in milk, may be one of many biological factors having an
      impact on the successful initiation of breast-feeding.

PMID- 17497077
TI  - A dissipative particle dynamics study of the realignment of a nanodroplet of a
      nematic in a weak external magnetic field.
AB  - We present a dissipative particle dynamics (DPD) approach for simulating the
      realignment of a nematic nanodroplet suspended in an isotropic fluid following a
      switch in the direction of an applied external magnetic field. The interaction of
      the mesogens with the external field is weak relative to the inter-molecular
      interactions. The simulations were used to investigate the way orientational
      equilibrium is re-established. The results reveal that the realignment process of
      the nanodroplet is consistent with its fluid structure. The reorientation of the
      nanodroplet as a whole is found to be caused by an internal structural
      rearrangement rather than a coherent rotation of the centres of mass of the
      mesogens about the centre of the nanodroplet. The switch in the field direction
      furthermore is found to induce a transient spatial variation in the orientational
      order of the long axes of the mesogens: the orientational order parameters
      decreases on moving from the core of the nanodroplet to the surface in contact
      with the isotropic environment. The results highlight differences between the
      time evolution of the orientation of the long molecular axes in the field and the
      rotations of the centres of mass of the mesogens about the centre of the
      nanodroplet.

PMID- 17497076
TI  - Food intake and plasma ghrelin response during potato-, rice- and pasta-rich test
      meals.
AB  - OBJECTIVE: Complex carbohydrates such as potato, rice and pasta are frequently
      consumed accompaniments of meat meals and have different effects on satiety, food
      intake, glucose, and insulin concentrations. The orexigenic gastric hormone
      ghrelin contributes to feeding regulation and as yet it is unknown whether there
      is any differential ghrelin response to these starchy food items corresponding to
      their effects on food intake. METHODS: In 11 subjects the effect of satiating
      amounts of potatoes, rice or pasta consumed together with 150 g pork steak was
      examined on hunger/satiety ratings, food intake, plasma insulin, glucose and
      ghrelin concentrations. RESULTS: All meals led to comparable quantities of food
      intake while energy intake was significantly lower after potatoes. Satiety/hunger
      ratings were significantly different from basal for the entire 4 h period after
      rice and pasta meals, while they had returned to basal during the 4th hour after
      potatoes. After rice and pasta insulin rose significantly for 4 h. Ghrelin
      decreased during the 2nd and 3rd hour. In contrast potatoes stimulated insulin
      for the initial 2 h only while ghrelin rose significantly by 120 pg/ml over the 4
      h period. A significant correlation was observed between ghrelin and hunger
      ratings while subsequent second meal food and energy intake did not differ
      irrespective of the preceding ghrelin concentration. CONCLUSION: Compared to rice
      and pasta satiating amounts of potatoes coingested with meat result in lower
      energy intake and postprandial insulin concentrations, which is not
      counterbalanced during subsequent food intake despite higher ghrelin
      concentrations. The present data support the concept that ghrelin can affect
      hunger sensations but not necessarily food and energy intake.

PMID- 17497078
TI  - Quantifying the A1AR distribution in peritumoural zones around experimental F98
      and C6 rat brain tumours.
AB  - Quantification of growth in experimental F98 and C6 rat brain tumours was
      performed on 51 rat brains, 17 of which have been further assessed by 3D tumour
      reconstruction. Brains were cryosliced and radio-labelled with a ligand of the
      peripheral type benzodiazepine-receptor (pBR), (3)H-Pk11195 [(1-(2-chlorophenyl)
      N-methyl-N-(1-methyl-propylene)-3-isoquinoline-carboxamide)] by receptor
      autoradiography. Manually segmented and automatically registered tumours have
      been 3D-reconstructed for volumetric comparison on the basis of (3)H-Pk11195
      based tumour recognition. Furthermore automatically computed areas of -300 microm
      inner (marginal) zone as well as 300 microm and 600 microm outer tumour space
      were quantified. These three different regions were transferred onto other
      adjacent slices that had been labelled by receptor autoradiography with the A(1)
      Adenosine receptor (A(1)AR)-ligand (3)H-CPFPX ((3)H-8-cyclopentyl-3-(3
      fluorpropyl)-1-propylxanthine) for quantitative assessment of A(1)AR in the three
      different tumour zones. Hence, a method is described for quantifying various
      receptor protein systems in the tumour as well as in the marginal invasive zones
      around experimentally implanted rat brain tumours and their representation in the
      tumour microenvironment as well as in 3D space. Furthermore, a tool for
      automatically reading out radio-labelled rat brain slices from auto radiographic
      films was developed, reconstructed into a consistent 3D-tumour model and the
      zones around the tumour were visualized. A(1)AR expression was found to depend
      upon the tumour volume in C6 animals, but is independent on the time of tumour
      development. In F98 animals, a significant increase in A(1)AR receptor protein
      was found in the Peritumoural zone as a function of time of tumour development
      and tumour volume.

PMID- 17497079
TI  - Antibacterial activity of four glass ionomer cements used in atraumatic
      restorative treatment.
AB  - The in vitro antibacterial activity of four glass ionomer cements (Fuji IX, Ketac
      Molar, Vidrion R and Vitromolar) indicated for Atraumatic Restorative Treatment
      (ART) was studied against strains of bacteria involved in the development of oral
      diseases, Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus
      and Actinomyces viscosus. The agar plate diffusion test was used for the
      cultures, which included chlorhexidine as a positive control. The results
      demonstrated that all the cements evaluated presented antibacterial activity.
      Based on the results of this study, it can be concluded that Fuji IX and Ketac
      Molar presented the most effective antibacterial activity considering the ART
      approach.

PMID- 17497080
TI  - P-glycoprotein in proteoliposomes with low residual detergent: the effects of
      cholesterol.
AB  - PURPOSE: There is evidence that cholesterol affects the ATPase and transport
      functions of P-glycoprotein (P-gp). To study the influence of cholesterol on P-gp
      in a well defined lipid environment, we reconstituted P-gp in egg
      phosphatidylcholine (PhC) and PhC/cholesterol proteoliposomes with negligible
      residual amounts of detergents. MATERIALS AND METHODS: P-gp proteoliposomes were
      prepared by continuous dialysis from micelles consisting of P-gp, lipids, sodium
      dodecyl sulfate and cholate. Basal and modulator-induced ATPase activities were
      studied in an established enzyme assay. Modulator affinities to P-gp and to the
      lipid bilayers were determined by equilibrium dialysis. RESULTS: In the absence
      of cholesterol the basal ATPase activity was six fold lower than in the presence
      of 20 or 40% cholesterol, and no P-gp binding and ATPase induction was detected
      for the tested modulators verapamil and progesterone. In proteoliposomes
      containing 20 and 40% cholesterol, respectively, the modulators showed
      significant P-gp binding and ATPase activation. The concentration of the
      modulators for half maximal activation of the ATPase was higher with 40% than
      with 20% cholesterol. CONCLUSIONS: Cholesterol influences P-gp in three ways: (a)
      it enhances its basal ATPase activity, (b) it renders P-gp sensitive towards the
      modulators verapamil and progesterone and (c) it affects the modulator
      concentration at half maximal ATPase activation.

PMID- 17497081
TI  - Assessment of the "skin reservoir" of urea by confocal Raman microspectroscopy
      and reverse iontophoresis in vivo.
AB  - PURPOSE: To demonstrate the "skin reservoir" of urea by confocal Raman
      microspectroscopy in vivo and to evaluate its impact on the non-invasive
      monitoring of the analyte by reverse iontophoresis. METHODS: Urea was extracted
      iontophoretically over a 2-h period across the skin of adult volunteers and
      patients with chronic kidney disease. Confocal Raman microspectroscopic profiles
      of skin were recorded before and after 30 min of current application. RESULTS:
      Urea extraction was higher at the beginning of current passage, but then
      decreased to achieve stable values after 2 h of iontophoresis. After 30 min of
      iontophoresis, the Raman spectra highlighted a clear depletion of urea at the
      surface of the skin. Lactate distribution was also modified both at the surface
      and deeper into the skin. CONCLUSIONS: A source of urea in the skin, unrelated to
      the concentration circulating in the blood, was strongly suggested by extracted
      urea flux observed over time and by the Raman spectroscopy. This "urea reservoir"
      must be removed before systemic urea levels can be non-invasively monitored by
      reverse iontophoresis.

PMID- 17497082
TI  - Structural features of GmIRCHS, candidate of the I gene inhibiting seed coat
      pigmentation in soybean: implications for inducing endogenous RNA silencing of
      chalcone synthase genes.
AB  - Most commercial soybean varieties have yellow seeds due to loss of pigmentation
      in the seed coat. The I gene inhibits pigmentation over the entire seed coat,
      resulting in a uniform yellow color of mature harvested seeds. We previously
      demonstrated that the inhibition of seed coat pigmentation by the I gene results
      from post-transcriptional gene silencing (PTGS) of chalcone synthase (CHS) genes.
      Little is known about the structure of the I gene and the mechanism by which it
      induces PTGS of CHS genes. Here, we report a candidate of the I gene, GmIRCHS,
      which consists of a 5'-portion of a DnaJ-like gene containing a promoter region
      and a perfect inverted repeat (IR) of 1.1-kb truncated CHS3 sequences (5'
      DeltaCHS3 and 3'-DeltaCHS3). RT-PCRs and RNase protection assay indicated the
      existence of the read-through product from 5'-DeltaCHS3 to 3'-DeltaCHS3 and the
      dsRNA region of DeltaCHS3, suggesting that dsRNA of DeltaCHS3 could be
      transcribed from GmIRCHS and could induce PTGS of CHS genes. Moreover, the IR
      structure of DeltaCHS3 in GmIRCHS was lost in the soybean mutants in which I was
      changed to i, supporting the conclusion that GmIRCHS is the I gene.

PMID- 17497083
TI  - Histo-blood group antigen expression and proliferative activity of fibroblasts
      treated with dental monomers.
AB  - The present work is focused on examining the effect of the structurally similar
      dental monomers bis-GA and bis-GMA on the expression of histo-blood group
      antigens (HBGAs) in comparison with fibroblast vitality and proliferation. The
      fibroblast cell line McCoy-Plovdiv was cultivated in a serum-free medium and was
      treated with both monomers. Cell vitality was measured by the crystal violet
      test. Mitotic index and cell morphology were assessed. An immunocytochemical
      technique was applied to follow the expression of proliferative antigens PCNA and
      Ki-67 and of HBGA. The expression level of HBGA was measured by an improved pixel
      selection algorithm with proprietary software. The lowest concentration of 2.5
      micromol/L did not significantly affect morphology, vitality, or proliferation
      activity. Interestingly, the quantitative analysis revealed augmented expression
      of HBGA B at 2.5 micromol/L. The higher concentrations of the dental monomers
      reduced cell vitality and mitotic indices and altered proliferative antigen
      expression. Bis-GA proved to be more toxic than bis-GMA and caused more prominent
      alterations including greater enhancement of HBGA B expression. We present novel
      evidence for altered expression of proliferative antigens and enhanced expression
      of HBGA B in fibroblasts treated with dental monomers bis-GA and bis-GMA
      suggesting that these substances affect cell morphology, proliferative activity,
      and antigenic profile.

PMID- 17497084
TI  - [High-performance medicine and humanitarian principles].

PMID- 17497085
TI  - [Epidemiology of hepatitis B in Germany].
AB  - BACKGROUND AND PURPOSE: Little is known about the epidemiology of chronic
      hepatitis B virus (HBV) infection in Germany. The present study analyzes
      demographic, socioeconomic and virologic data of a cohort of German HBV-infected
      patients. PATIENTS AND METHODS: As a project of the Hepatitis Competence Network,
      250 outpatients with chronic HBV infection were included during the last 5 years.
      RESULTS: Mean age was 40.5+/-14.6 years; 63.2% were men. HBV-DNA was negative by
      polymerase chain reaction in 12.8%; alanine aminotransferase ALT) was normal in
      56.3%; even at DNA levels>1 million copies/ml ALT was normal in 38%
      ("immunotolerance"). About one third of patients were born in Germany, Turkey or
      one of 34 other countries. The unemployment rate in migrants from Turkey and
      other countries was more than three times the rate of subjects born in Germany;
      this difference, however, is the same in non-HBV-infected subjects. In the total
      cohort HBeAg-negative subjects were more frequent than HBeAg-positive subjects
      (66.4% vs. 33.6%). About 40% of patients with a liver biopsy had significant
      fibrosis (F2-4). Multivariate regression showed that significant fibrosis was
      associated only with age and ALT, but not with HBV-DNA or other variables. 38.4%
      of subjects had antiviral therapy; the rate of therapy increased with increasing
      DNA and ALT. The majority of treated patients received lamivudine (58%), adefovir
      (31%), or both (5%). Only 3% each received interferon or other antivirals.
      CONCLUSION: The present cohort study shows that about two thirds of HBV-infected
      subjects who live in the Ruhrgebiet originate from migrants many of whom have
      significant economic problems. Special programs should be designed for migrants
      in order to detect HBV infection and to inform infected subjects about their
      individual and infectious risks.

PMID- 17497086
TI  - [Congenital left ventricular aneurysms and diverticula. Pathophysiology, clinical
      relevance, and treatment].
AB  - A congenital left ventricular aneurysm or diverticulum is a rare cardiac
      malformation described in 418 cases since the first description in 1816, being
      associated with other cardiac, vascular or thoracoabdominal abnormalities in
      about 75%. It appears to be a developmental anomaly, starting in the 4th
      embryonic week. Diagnosis can be made after exclusion of coronary artery disease,
      local or systemic inflammation or traumatic causes as well as cardiomyopathies.
      Clinically, most congenital left ventricular aneurysms and diverticula are
      asymptomatic, but some of them may cause systemic embolization, heart failure,
      valvular regurgitation, ventricular wall rupture, ventricular tachycardia, or
      sudden cardiac death. Diagnosis is established by imaging studies such as
      echocardiography, magnetic resonance imaging or left ventricular angiography,
      visualizing the structural changes and accompanying abnormalities. Mode of
      treatment has to be individually tailored and depends on clinical presentation,
      accompanying abnormalities and possible complications, options include surgical
      resection, especially in symptomatic patients, anticoagulation after systemic
      embolization, radiofrequency ablation or implantation of a cardioverter
      defibrillator in case of symptomatic ventricular tachycardias, occasionally
      combined with class I or III antiarrhythmic drugs. Because of the usually benign
      course of congenital left ventricular aneurysms and diverticula in the adulthood,
      most of them can be managed conservatively.

PMID- 17497087
TI  - [External and internal financing in health care].
AB  - The objective of this contribution is to characterize the functional and
      institutional features of the German health-care system. This takes place after a
      short introduction and examination of the ongoing debate on health care in
      Germany. External funding describes the form of revenue generation. Regarding
      external funding of the German health care system, one of the favored
      alternatives in the current debate is the possibility of introducing per capita
      payments. After a short introduction to the capitation option, focus is on the so
      called health fund that is currently debated on and being made ready for
      implementation in Germany, actually a mixed system of capitation and
      contributions based on income. On the other hand, internal funding is the method
      of how different health-care services are purchased or reimbursed. This becomes a
      rather hot topic in light of new trends for integrated and networked care to
      patients and different types of budgeting. Another dominating question in the
      German health-care system is the liberalization of the contractual law, with its
      "joint and uniform" regulations that have to be loosened for competition gains.
      After a discussion of the consequences of diagnosis-related groups (DRGs) in
      Germany, the article is concluded by a note on the political rationality of the
      current health-care reform for increased competition within the Statutory Health
      Insurance and its players as exemplified by the health fund. To sum up, it has to
      be said that the complexity and specific features of how the German system is
      financed seem to require ongoing reform considerations even after realization of
      the currently debated health-care reform law which, unfortunately, is dominated
      by political rationalities rather than objective thoughts.

PMID- 17497089
TI  - [The German program for disease management guidelines. Results and perspectives].
AB  - The Program for National Disease Management Guidelines (German DM-CPG Program) is
      a joint initiative of the German Medical Association (umbrella organization of
      the German Chambers of Physicians), the Association of the Scientific Medical
      Societies (AWMF), and of the National Association of Statutory Health Insurance
      Physicians (NASHIP). The program aims at developing, implementing and
      continuously updating best-practice recommendations for countrywide and regional
      disease management programs in Germany. Since 2003 twelve national guidelines
      (topics: asthma, chronic obstructive pulmonary disease, HI (Chronic heart
      failure), CVD (Chronic coronary heart disease) back pain, depression, several
      aspects of diabetes) have been produced by use of a standardized procedure in
      accordance with internationally consented methodologies. For countrywide
      dissemination and implementation the program uses a wide range of specialist
      journals, continuous medical education and quality management programs. So far,
      36 out of 150 national scientific medical associations, four allied health
      profession organizations, and twelve national consumer organizations have been
      participating in the DM-CPG Program. Studies to evaluate the program's effects on
      health-care providers' behavior and patients' outcomes are under way.

PMID- 17497088
TI  - [Gastroesophageal reflux: diagnostics and therapy of a widespread disease].

PMID- 17497090
TI  - [Occlusion of the femoral arteries in de novo AML].
AB  - BACKGROUND: Leukemic emboli in acute (AML) and chronic myelocytic leukemia (CML)
      are associated with hyperleukocytosis (>100,000/microl leukocytes) and most
      frequently detected at autopsy. They mainly occur in the small- and middle-sized
      arteries of lung and brain. Less frequently, leukemic emboli have also been
      observed in the cardiac chambers. The occlusion of large arteries by a leukemic
      embolus is a rare event. CASE REPORT: A 53-year-old woman was admitted with
      hyperleukocytosis and acute pain in her right leg. An occlusion of the right
      femoral arteries as the presenting symptom of a de novo AML (FAB M1/WHO: AML
      without maturation) with hyperleukocytosis was diagnosed. CONCLUSION: Leukemic
      emboli of large vessels are uncommon in leukemia with hyperleukocytosis. Most
      frequently, small- and middle-sized vessels of the brain and lung are affected.
      Leukemic emboli mainly occur in AML and CML in blast crisis and are rare in acute
      (ALL) and chronic lymphocytic leukemia (CLL). Risk factors are hyperleukocytosis
      and the expression of adhesion surface molecules which modulate blast-blast and
      endothelium interaction. Therapeutic options, apart from the immediate start of
      chemotherapy, are leukapheresis and embolectomy.

PMID- 17497091
TI  - [Pseudotumoral laryngeal tuberculosis].

PMID- 17497092
TI  - [New perspectives in GINA Asthma Guideline 2006].
AB  - The GINA (Global Initiative for Asthma) 2006 guideline contains far-reaching
      innovations in asthma management and control. The dose and choice of recommended
      medication depend on the degree of asthma severity and the quality of asthma
      control, rather than using the known stepwise severity approach. This flexible
      scheme gives the treating physician great freedom in the choice of substance
      used. However, the coexistence of the nonetheless valid four-degree severity
      grading with the new five-degree therapy scheme may cause confusion. The asthma
      control-guided new treatment recommendations are based on the experience with the
      GOAL (Gaining Optimal Asthma controL) trial. Altogether, the GINA 2006 guideline
      represents a shift of paradigm in asthma management. The efficacy of these
      recommendations and their practicability, however, have still to be proven. The
      aim of this review is, first, to introduce these new aspects and, second, to
      critically discuss advantages and potential disadvantages.

PMID- 17497093
TI  - Integration of novel agents into combined-modality treatment for rectal cancer
      patients.
AB  - BACKGROUND: With optimized local treatment--achieved through preoperative
      radiochemotherapy (RCT) and total mesorectal excision (TME) surgery--distant
      metastases are by far the predominate sites of tumor failure in rectal cancer
      today. The challenge is to integrate more effective systemic therapy into
      combined-modality programs. MATERIAL AND METHODS: Capecitabine, oxaliplatin,
      irinotecan as well as targeted therapies improved results for colorectal cancer
      patients when treated in the metastatic and adjuvant setting. These agents have
      now been incorporated into phase I-II studies for rectal cancer. RESULTS: Phase
      I/II studies with combination chemotherapy suggest higher pathologic complete
      response (pCR) rates in the range of 15-25% and improved tumor regression
      compared with 5-fluorouracil (5-FU) RCT alone. However, the pCR rate is an early
      surrogate endpoint that may not necessarily translate into improved long-term
      outcomes. For some studies, this increased pCR rate is associated with an
      increase in acute toxicity--and data on long-term toxic sequelae are not yet
      available. Further challenges are to define the best sequence of combinations,
      including neoadjuvant combination chemotherapy prior to RCT, the role of
      postoperative chemotherapy, and the best sequence of targeted therapies.
      CONCLUSION: Phase III trials are needed to determine, if these novel combination
      regimens offer an advantage compared with 5-FU-based combined modality. These
      studies have now been started in Germany (CAO/ARO/AIO-04), Europe (PETACC 6), and
      the USA (NSAPB-R04, E5204 Intergroup Trial).

PMID- 17497094
TI  - Craniospinal radiotherapy in adult medulloblastoma.
AB  - PURPOSE: To evaluate the outcome and prognostic factors of adult patients with
      medulloblastoma. PATIENTS AND METHODS: 26 adult medulloblastoma patients with a
      median age of 27 were subjected to craniospinal radiotherapy. A dose of 30.6 Gy
      with 1.8 Gy/fraction/day was prescribed to M0 patients, while 36 Gy were to be
      applied in patients with positive cerebrospinal liquor findings. The posterior
      fossa was boosted to 54 Gy. While 20 patients underwent external-beam radiotheray
      alone, only six received sequential adjuvant chemotherapy. RESULTS: Male/female
      ratio was 1.2. Preradiotherapy Karnofsky performance status was recorded as
      median 100%. 50% were classified as poor risk (n = 10, subtotal resection; n = 3,
      M+). The median follow-up time was 46.5 months. The 5-year actuarial survival
      rates for recurrence-free, distant metastasis-free, disease-free, and overall
      survival were 82.5%, 90.8%, 73.5%, and 89.7%, respectively. Patient
      characteristics, treatment factors and tumor characteristics failed to show any
      significance in univariate analysis. Grade 3 or 4 late morbidities were not
      observed. CONCLUSION: Yet, the current standard of care seems to remain
      craniospinal irradiation after maximal surgical resection of the primary neoplasm
      without clear indications for adjuvant chemotherapy.

PMID- 17497095
TI  - Long-term follow-up of patients with pituitary macroadenomas after postoperative
      radiation therapy: analysis of tumor control and functional outcome.
AB  - PURPOSE: Evaluation of long-term tumor control, normalization of hormonal
      hypersecretion, including incidence and time course of pituitary dysfunction
      following postoperative radiotherapy of pituitary macroadenomas. PATIENTS AND
      METHODS: In a retrospective study, the data of 87 patients with pituitary
      macroadenomas (61 non-secreting adenomas, 26 secreting adenomas) treated between
      1984 and 1994 were analyzed. All patients underwent surgery and received
      postoperative external-beam radiotherapy with a mean dose of 50.4 Gy (range 46-54
      Gy). RESULTS: After a follow-up of 15 years the local tumor control rate achieved
      was 93.0% for non-secreting adenomas and 100% for secreting adenomas,
      respectively. Normalization of endocrine hypersecretion was noted in 24 of 26
      patients (92%). Detailed endocrinological follow-up data were analyzed by an
      experienced endocrinologist in 77 patients. After a median follow-up of 10.54
      years (mean 10.22; range 1.39-20.75 years), in 75 of 77 patients (97%) a
      hypopituitarism was observed (partial hypopituitarism, n = 28 [36%],
      panhypopituitarism, n = 47 [61%]), and 68 out of 77 patients (88%) showed
      evidence of radiotherapy-induced pituitary disorders. The somatotropic function
      was most commonly affected, followed by gonadal, thyroid and adrenal function.
      The gonadal axis showed to be the first to be disturbed. 67 patients (87%)
      required a hormone replacement therapy. CONCLUSION: Radiotherapy after pituitary
      surgery is highly effective in reducing hormonal hypersecretion and preventing
      recurrences of pituitary adenomas. However, pituitary insufficiencies are
      commonly observed after radiotherapy requiring a close follow-up to ensure timely
      diagnosis of pituitary dysfunction and an early inception of hormone replacement
      therapy.

PMID- 17497096
TI  - Differential expression of egr1 and activation of microglia following irradiation
      in the rat brain.
AB  - BACKGROUND: Little is known about the immediate effects of whole-brain gamma
      irradiation. The authors hypothesize that Egr1 as an immediate early gene and
      microglia both participate in early reactions. MATERIAL AND METHODS: Both,
      expression of Egr1 and cellular distribution were studied in a temporal sequence
      in different brain regions of rats subjected to irradiation with 10 Gy. Brain
      tissue was examined using immunohistochemistry, real-time RT-PCR (reverse
      transcription-polymerase chain reaction), and Western blotting. RESULTS:
      Astroglia and oligodendroglia showed increased Egr1 immunoreactivity within the
      first hours following irradiation. This was accompanied by a strong peak in CD68
      immunoreactivity histologically attributable to activated microglia. A high
      constitutive expression of Egr1 protein in the nuclei of activated neurons was
      reduced following irradiation and RT-PCR demonstrated significantly reduced
      levels of egr1-lv as a neuronal activity-related mRNA variant. CONCLUSION: The
      induction of Egr1 in glial cells, as well as the activation of microglia take
      place earlier than histological changes reported so far. The authors revealed a
      temporal sequence of reactions that point toward the initiation of an immediate
      inflammatory response including reduced neuronal activity.

PMID- 17497097
TI  - Combination of EGFR/HER2 tyrosine kinase inhibition by BIBW 2992 and BIBW 2669
      with irradiation in FaDu human squamous cell carcinoma.
AB  - PURPOSE: To investigate the effect of the dual EGFR/HER2 (ErbB2) tyrosine kinase
      inhibitors BIBW 2992 and BIBW 2669 on proliferation and clonogenic cell survival
      of FaDu human squamous cell carcinoma in vitro, and on tumor growth after single
      dose irradiation in nude mice. MATERIAL AND METHODS: Cell proliferation, cell
      cycle distribution and clonogenic cell survival after irradiation were assayed
      with and without BIBW 2992 or BIBW 2669 (3, 30, and 300 nM) in vitro. Tumor
      volume and tumor growth delay (GD(V2)) were determined in tumors growing in NMRI
      (nu/nu) nude mice, treated with (a) BIBW 2992 (20 mg kg(-1) body weight orally),
      BIBW 2669 (3-4 mg kg(-1) body weight orally) or carrier until a final tumor
      diameter of 15 mm, or, (b) 3 days before a 20-Gy single-dose irradiation or, (c)
      after a 20-Gy single-dose irradiation until reaching the final tumor diameter.
      RESULTS: BIBW 2992 and BIBW 2669 significantly increased the doubling time of
      FaDu cells in vitro. A marked dose-dependent antiproliferative effect with
      blockade of the cells in G0/G1-phase of the cell cycle was found. Incubation with
      BIBW 2669 or BIBW 2992 for 3 days marginally increased radiosensitivity of FaDu
      cells in vitro. For BIBW 2992, this effect was statistically significant (p =
      0.006). Daily oral application of BIBW 2669 or BIBW 2992 in mice bearing
      unirradiated FaDu tumors showed a marked antiproliferative effect with a
      significant prolongation of tumor growth delay (p < 0.0001). After drug
      application for 3 days, followed by 20-Gy single-dose irradiation, a slight
      effect of both drugs on tumor growth delay was seen. For BIBW 2669, this effect
      was statistically significant (p = 0.007). However, this effect disappeared when
      tumor volumes were normalized to the time point of irradiation suggesting that
      both drugs showed no or only a slight radiosensitizing effect in vivo. Daily
      application of BIBW 2669 or BIBW 2992 after a single-dose irradiation showed a
      clear inhibition of tumor growth with a significantly longer tumor growth delay
      after drug treatment compared to control tumors (p < 0.002). Enhancement ratios
      were smaller for irradiated than for unirradiated tumors, suggesting an additive
      effect for combinations with radiotherapy. In all treatment arms, the effects of
      BIBW 2669 were not significantly different from BIBW 2992. CONCLUSION: BIBW 2669
      and BIBW 2992 showed a clear antiproliferative effect in vitro, whereas
      radiosensitization was only marginal. The present data are the first to show an
      effect of combined irradiation and dual EGFR/ErbB2 inhibition on tumor growth
      delay in vivo. Further preclinical investigations using fractionated irradiation
      schedules and local tumor control as experimental endpoint are needed to evaluate
      a possible curative potential for the combination treatment.

PMID- 17497098
TI  - Technical improvement of pO(2) measurements in breast cancer: investigation of
      the feasibility in patients and in vitro validation of the method.
AB  - PURPOSE: Investigating tumor oxygenation in breast cancer with the Eppendorf
      device is hampered by the deep location and inadequate fixation of the tumor
      within the breast. In order to ensure the correct site of pO(2) measurements,
      guiding aids were introduced and the reliability of the refined method was
      evaluated. MATERIAL AND METHODS: For guidance of the needle electrode, a metal
      trocar was inserted up to the tumor rim. Its positioning and all transtumoral
      tracks of the needle electrode were monitored continuously by ultrasonography.
      Thus, 150 tumor measurements in 148 patients were evaluated. In a phantom, the
      possible influence of the metal trocar was assessed and the measurements of two
      histographs with five different needle electrodes were compared. RESULTS: In 88%
      of measurements (132/150) complete or partial sonographic demarcation of the
      tumor was possible. 83.2% of the tracks (437/525) could be controlled by
      ultrasonography. Overall, in 60% of measurements (90/150) all values derived
      reliably from within the tumor. In vitro, an influence of the metal trocar on the
      measurements could be excluded. Differences between histographs were in
      accordance with tolerance limits. CONCLUSION: From theoretical considerations and
      the phantom experiments a significant negative impact of the technical
      modifications could be excluded. Instead, the method described here showed to be
      beneficial in measuring tumor oxygenation in breast tumors. The authors strongly
      advise to consider exclusively intratumoral pO(2) values as proven by
      ultrasonography for oxygenation profiling, as in 40% of all measurements the
      origin of single pO(2) values or tracks was questionable.

PMID- 17497099
TI  - Thermoplastic patient fixation: influence on chest wall and target motion during
      radiotherapy of lung cancer.
AB  - BACKGROUND AND PURPOSE: Several methods have been developed to reduce tumor
      motions and patient movements during radiotherapy of lung cancer. In this study,
      a multislice CT-based analysis was performed to examine the effect of a
      thermoplastic patient immobilization system on the chest wall and tumor motions.
      PATIENTS AND METHODS: Ten patients with stage II-IV lung cancer were enrolled
      into the study. According to tumor localization, five patients had peripheral,
      and five patients central lung cancer (T2-T4). In total, six series of
      measurements were made with a multislice CT scanner, both with and without mask
      fixation, in normal breathing, at maximal tidal volume inhalation, and at maximal
      tidal volume exhalation. RESULTS: Movements of chest wall, diaphragm and tumor,
      with and without mask, under different breathing conditions were registered. With
      the use of the immobilization system, no significant difference was found in
      diaphragmatic movements (mean deviation of diaphragm: 41.7-40.5 mm to the right,
      and 40.5-36.8 mm to the left side) and in tumor motions (mean deviation of tumor:
      15.3-12.4 mm in craniocaudal, and 11.5-8.8 mm in posterolateral direction, mean
      medial deviation: 4.6-4.1 mm, mean lateral deviation: 7.2-5 mm). Significant
      differences were observed concerning tumor motions in anteroposterior direction
      (mean: 8.9-6.3 mm) and transverse chest movements in anteroposterior direction.
      CONCLUSION: Besides the advantage of optimal patient positioning, the movements
      of the bony chest wall can be considerably reduced by using the immobilization
      system. However, this fixation system has limitations concerning its suitability
      for minimizing tumor motions.

PMID- 17497100
TI  - Carcinomatous meningitis appearing as acoustic neuromas: two cases.
AB  - BACKGROUND: For acoustic neuromas, stereotactic radiotherapy (radiosurgery or
      stereotactic fractionated radiotherapy) has been established as an important
      alternative to microsurgery. In most cases initial symptoms are slow progression
      of unilateral hearing loss, tinnitus or vertigo or acute hearing loss with
      vertigo. MRI scan shows a contrast-enhancing tumor within the inner auditory
      channel. If the patient undergoes primary radiotherapy, diagnosis is usually not
      verified histologically. Therefore, careful evaluation of the medical history is
      mandatory despite a typical appearance on the MRI scan. If medical history does
      not match with acoustic neuroma, further diagnostics are necessary to rule out
      infectious disease or carcinomatous meningitis. CASE REPORT: Two patients with
      hearing loss, vertigo and the diagnosis of acoustic neuromas by MRI scan were
      referred for radiotherapy. In both cases the symptoms progressed very rapidly,
      not typical of acoustic neuromas, and in both patients repeated liquor puncture
      finally revealed carcinomatous meningitis. One patient died during therapy; in
      the second patient intrathecal chemotherapy and additional radiotherapy of the
      skull base led to partial remission continuing for several months. CONCLUSION:
      Before primary radiotherapy of small intrameatal lesions diagnosis must be
      reassessed carefully. This is especially true for bilateral lesions suspicious
      for acoustic neuromas and rapid progression and persistence of clinical symptoms
      where carcinomatous meningitis has to be taken into account.

PMID- 17497101
TI  - [Impact of prophylactic HPV vaccines on dermatology and venereology].
AB  - Prophylactic HPV L1 VLP quadrivalent and bivalent vaccines are of great
      importance for patients seen by dermatologists and venereologists. Both vaccines
      protect against HPV16- and HPV18-associated anogenital cancers, as well as
      cancers of the mouth, the upper respiratory tract and skin, especially of the
      fingers and periungual region. The quadrivalent HPV6, 11, 16, 18 vaccine also
      prevents anogenital warts (condylomata acuminata) which are the most common
      benign tumors of this body region. HPV-vaccination (Gardasil) has been approved
      in Germany since October 2006 for young girls between 9-16 and young women
      between 16-26 years of age. Many experts feel that boys and young men should also
      be vaccinated. Men would profit from a vaccine that protects against HPV
      infections, especially anogenital warts, as well as penile and anal carcinomas.
      In immunosuppressed organ transplant recipients and HIV-positive individuals, HPV
      can be widespread, chronic and often rapidly progressive to malignant tumors;
      thus these groups would greatly benefit from HPV immunization.

PMID- 17497102
TI  - [Prophylactic and therapeutic HPV immunization].
AB  - Papilloma viruses (PV) have been known to cause benign and malignant tumors in
      animals for more than 100 years. It took over 20 years to win general acceptance
      for their causative role in anogenital carcinomas in humans in particular in
      cervial carcinoma. Extensive research has led to the development of a
      prophylactic vaccine which is now commercially available. It remains to be
      investigated if HPV-specific therapeutic vaccines can be developed.

PMID- 17497103
TI  - [What does HPV vaccination mean for gynecologic cancer screening?].
AB  - Human papilloma viruses (HPV) of the high-risk type cause almost all cervical
      carcinomas and some other anogenital tumors. Development of a carcinoma is
      uncommon; most infections heal spontaneously. When carcinomas develop, the latent
      phase is at least 8, more often 15-30 years. A negative HPV test thus excludes
      the risk of developing cervical carcinoma for many years. The approved vaccine
      against HPV 6/11/16/18 and the soon-to-be-approved one against HPV 16/18 are
      extremely safe and effective. Vaccinated individuals are almost 100% protected by
      the vaccines containing virus-like particles. Current studies suggest that 70-80%
      of high-grade cervical neoplasias can be avoided, as well as other vaginal,
      vulvar, and anal neoplasias. The yearly costs for treating precursors of these
      cancers exceed the cost of vaccinating all girls born in a given year. Thus HPV
      vaccination is cost effective, even when a modified cancer screening program is
      retained.

PMID- 17497104
TI  - [Humoral and cellular immune response in HPV vaccination].
AB  - Human papillomaviruses (HPV) infect skin or mucosal epithelia causing warts and
      dysplasia. Infections with certain high-risk HPV types in the anogenital tract
      can lead to malignant transformation. Cervical cancer is the second most common
      malignant disease in young women responsible for 275000 deaths annually
      worldwide. More than 50% of sexually active people acquire HPV infections over
      their lifetime. Around 80% of infections remain subclinical and are cleared by
      the immune system. Recently prophylactic vaccines against the two most common
      high-risk types HPV16 and 18, and additionally low-risk types HPV6 and 11,
      respectively, have become available. We present an overview concerning recent
      knowledge on natural and vaccine-induced immunity against HPV infections.

PMID- 17497105
TI  - Is it possible to predict renal function in small animals using a multi-pinhole
      SPECT system.

PMID- 17497106
TI  - Targeting of matrix metalloproteinase activation for noninvasive detection of
      vulnerable atherosclerotic lesions.
AB  - INTRODUCTION: Inflammation plays an important role in vulnerability of
      atherosclerotic plaques to rupture and hence acute coronary events. The monocyte
      macrophage infiltration in plaques leads to upregulation of cytokines and
      metalloproteinase enzymes. Matrix metalloproteinases result in matrix dissolution
      and consequently expansive remodeling of the vessel. They also contribute to
      attenuation of fibrous cap and hence susceptibility to rupture. Assessment of
      metalloproteinase expression and activity should provide information about plaque
      instability.

PMID- 17497107
TI  - Estimation of coronary flow reserve by SPECT: myth or reality?

PMID- 17497109
TI  - Growing up and living with neurofibromatosis1 (NF1): a British Bangladeshi case
      study.
AB  - In this article, I analyse a narrative by Rohima(1), a Bangladeshi woman now
      living in the UK who was diagnosed in adulthood as having NF1
      (neurofibromatosis). While some themes in her narrative account resemble those of
      persons with NF1 in the general European and American population, other themes
      relate specifically to Bangladeshi cultural issues and practices. These
      particularly concern gender, sexual identity and marriage. As a young woman,
      Rohima's dark skin coloration and the tumors or lumps associated with her
      condition led her parents and relatives to regard her as unmarriageable and in
      effect, despite her evident intelligence and competence, to deny that she was a
      woman. Bangladeshi men and women alike found her appearance a bar to any social
      acceptability. Even after her marriage (to a non-Bangladeshi man), her family
      have been unwilling to accept her and her children fully into their kinship
      network. The article explores the consequences of genetic disorders such as NF1
      in cultures where social identity and concepts of personhood, particularly for
      women, are inextricably related to appearance and to judgements regarding
      marriageability.

PMID- 17497110
TI  - Genetics support to primary care practitioners - a demonstration project.
AB  - Primary care practitioners need to be supported by specialist genetics services
      to enable them to cope effectively with the expanding relevance of genetics to
      their patients. Genetic counselors could be effective in such a role. This
      exploratory project set out to improve the Primary-Tertiary interface through
      piloting such a service to general practice for 1 year. Tailored genetic
      educational outreach was delivered by a genetic counselor to ten randomly
      selected general practices in central England for 12 months. A range of services
      were provided to the practices these included facilitated genetic update
      sessions, a responsive advice service and referral guidelines. The service was
      evaluated through pre and post intervention questionnaires and via seven semi
      structured interviews. This article presents a description of the development and
      delivery of this service and also reports on the experiences of a sample of the
      participants. Participants reported positive attitudes to the service and said
      that they had gained knowledge and confidence, as well as recognized limitations
      and gaps in their current knowledge. The consistent link with a specialist
      genetics service provided by a genetic counselor had a positive impact during the
      project and participants have continued to utilize the genetic counselor for
      advice and support with genetic patient issues since the project was completed.
      This is the first example of this model of service provision. Further research,
      utilizing a larger sample and other measures of behavioral change needs to be
      carried out to assess whether this model should be adopted on a wider basis.

PMID- 17497108
TI  - Recommendations from multi-disciplinary focus groups on cascade testing and
      genetic counseling for fragile X-associated disorders.
AB  - The purpose of this paper is to report the outcome of a collaborative project
      between the Fragile X Research and Treatment Center at the Medical Investigation
      of Neurodevelopmental Disorders (M.I.N.D.) Institute at the University of
      California at Davis, the National Fragile X Foundation (NFXF), and the Centers
      for Disease Control and Prevention (CDC). The objective of this collaboration was
      to develop and disseminate protocols for genetic counseling and cascade testing
      for the multiple disorders associated with the fragile X mental retardation 1
      (FMR1) mutation. Over the last several years, there has been increasing insight
      into the phenotypic range associated with both the premutation and the full
      mutation of the FMR1 gene. To help develop recommendations related to screening
      for fragile X-associated disorders, four, two day advisory focus group meetings
      were conducted, each with a different theme. The four themes were: (1) fragile X
      associated tremor/ataxia syndrome (FXTAS); (2) premature ovarian failure (POF)
      and reproductive endocrinology; (3) psychiatric, behavioral and psychological
      issues; and (4) population screening and related ethical issues.

PMID- 17497111
TI  - [Efficacy of atypical antipsychotics in patients with Alzheimer's dementia. CATIE
      AD-Study (Clinical Antipsychotic Trials of Intervention Effectiveness Alzheimer's
      Disease)].

PMID- 17497112
TI  - [The development of internal medicine. Observations within the context of all
      medicine and future prospects].

PMID- 17497113
TI  - [Surgical resection of the thyroid and parathyroid glands].
AB  - The main indication for surgery of the thyroid gland is the resection of nodular,
      suspicious or hyperfunctioning tissue. Following thyroidectomy, L-thyroxine
      therapy is initiated adjusted to the remnant thyroid function. To prevent
      recurrence of a multinodular goiter, supplementation with iodine is strongly
      recommended. The management of patients with differentiated thyroid cancer
      depends on risk stratification. Although large prospective studies are missing,
      low-risk patients probably do not benefit from total thyroid ablation and
      lifelong thyroxine suppression therapy. As a result of impaired parathyroid
      function or resection of the parathyroid glands for hyperparathyroidism, acute or
      chronic hypocalcaemia can develop. If treatment with oral calcium is
      insufficient, the addition of a vitamin D analogue is necessary. This requires
      close monitoring to avoid renal or other hypercalcaemic complications.

PMID- 17497114
TI  - Lymphotoxin-alpha and galectin-2 SNPs are not associated with myocardial
      infarction in two different German populations.
AB  - Recent data provided strong evidence for the association of single nucleotide
      polymorphisms (SNPs) in the lymphotoxin-alpha (LTA) and galectin-2 (LGALS2) genes
      with myocardial infarction (MI) in a Japanese population. For populations of
      other genetic background, the relevance of these polymorphisms in the
      pathogenesis of MI remains controversial. We aimed to define the role of LTA and
      LGALS2 SNPs in two German MI populations with markedly different ascertainment
      strategies. Two different MI populations were studied. In the first population,
      MI patients were ascertained by a strong family history of MI (n = 1214).
      Controls were unrelated disease-free participants of the study (n = 1080). The
      second population included patients suffering from sporadic (nonfamilial) MI from
      the German KORA register (n = 607). The control group consisted of participants
      of the WHO MONICA survey in Germany (n = 1492). TaqMan assays were used to
      determine the genotypes of 4 SNPs in the LTA genomic region and 1 SNP in the
      LGALS2 gene. Single SNPs in both genomic regions as well as haplotypes in the LTA
      genomic region were tested for association in various models of inheritance. No
      association with MI could be found for any of the examined SNPs in the LTA
      genomic region and LGALS2 gene, or for haplotypes spanning the LTA genomic
      region. In two MI populations of European descent with markedly different
      ascertainment strategies, we were not able to identify a significant association
      of SNPs in the LTA genomic region or the LGALS2 gene with MI. These variants are
      unlikely to play a significant role in populations of European origin.

PMID- 17497115
TI  - MIM: a multifunctional scaffold protein.
AB  - The protein "missing in metastasis", known as MIM, has been characterised as an
      actin-binding scaffold protein that may be involved in cancer metastasis. In this
      paper, we summarise the literature surrounding the role of MIM in actin and
      membrane dynamics and in signalling to transcription via the sonic hedgehog
      pathway. MIM is postulated to have many potential activities, including a BAR
      like domain termed the IMD (IRS-MIM domain), which can interact with membranes to
      induce membrane deformation and also with actin and the small GTPase Rac. How
      this multifunctional protein and its close relative ABBA-1 regulate cellular
      behaviour is still very much an open question.

PMID- 17497116
TI  - [Management of metaphyseal nonunions of the femur with retrograde nailing].
AB  - We report on the therapy of two hypertrophic, metaphyseal nonunions of the distal
      femur by retrograde nailing. Two patients with an old nonunion were successfully
      treated only by interlocking the retrograde nail according to the principle of
      transfixation. Both cases illustrate that an angular stable fixation might be
      critical to bony consolidation in the metaphyseal region. If toggling of the nail
      within the medullary cavity is limited by interlocking at appropriate positions,
      retrograde intramedullary nailing will provide angular stable fixation.

PMID- 17497117
TI  - [Minimally invasive fixed-angle plate osteosynthesis for complex humeral
      fracture].
AB  - Two cases of complex humeral fractures are presented that were stabilised by a
      minimally invasive approach using a long fixed-angle humerus plate. Postoperative
      treatment and bone healing were uneventful. Followed by careful preparation of a
      proximal deltoid split access and a subtle dissection of the m. brachialis the
      plate can be placed epiperiosteally and the screws can be applied using
      the"moving window" principle. Fixed-angle fixation with the internal fixator
      principle allows treating the radial nerve in the direct neighbourhood of the
      plate with circumspect without full contact between the bone and the plate. The
      technique can be recommended for complex combined meta- and diaphyseal fractures
      of the upper two-thirds of the humerus.

PMID- 17497118
TI  - [Balloon assisted cement application for stable fixation of pedicle screws in
      osteoporosis].
AB  - In Germany more than 40,000 patients suffer from osteoporotic vertebral fractures
      every year. Most of these fractures do not require operative stabilisation.
      However, if surgical stabilisation is necessary, stable fixation of
      transpedicular implants will be difficult to obtain. In a case study we report on
      the possibility of a kyphoplasty-guided technique for stable pedicle screw
      fixation.

PMID- 17497119
TI  - [Management of bicondylar fractures of the tibial plateau with unilateral fixed
      angle plate fixation].
AB  - BACKGROUND: This study was initiated to evaluate early results of a locked screw
      plate for unilateral fixation of bicondylar fractures of the tibial plateau.
      Emphasis was laid on malreduction, secondary loss of reduction, union rate, and
      infection. MATERIAL AND METHODS: A case series of patients with AO/ASIF 41-C type
      fractures treated with the less invasive stabilization system for the proximal
      lateral tibia (LISS PLT) were prospectively followed up until 11-13 months after
      surgery. Malreduction and malalignment were defined as an intra-articular step
      off of 2 mm or more or as a malalignment in the frontal or sagittal plane of more
      than 5 degrees. RESULTS: Sixty-eight patients with 69 fractures were involved.
      Fourteen fractures were open. Primary bone grafting was performed in 13 patients.
      Significant malreduction was seen in 16 patients. Sixty-two (91%) patients
      returned for follow-up. All but one fracture healed eventually. The number of
      infections was low (4 superficial, 1 deep). Nine patients had a significant loss
      of reduction. Of 54 patients outcome scores were good to excellent in 47 patients
      on the Lysholm score (average 87.2) and in 44 patients on the Rasmussen score
      (average 26.7). CONCLUSION: We concluded that unilateral locked screw plating is
      a good alternative in the treatment of problematic fractures of the tibial
      plateau that are associated with soft tissue damage and metaphyseal comminution.
      The reduction technique for exact alignment is demanding.

PMID- 17497120
TI  - [Horner's syndrome after fracture of the first rib].
AB  - Horner's syndrome after trauma is rare. After visual diagnosis, a search for the
      cause is urgent due to possible life threatening damage. Intracerebral bleeding
      and carotid dissection must be excluded. Traumatic Horner's syndrome often seems
      to be, as in the case described here, caused by a fracture of the first rib. As
      persistent symptoms are not described, conservative therapy is recommended.

PMID- 17497121
TI  - Are the polygenic architectures of resistance to Phytophthora capsici and P.
      parasitica independent in pepper?
AB  - The pepper accession Criollo de Morelos 334 is the most efficient source of
      resistance currently known to Phytophthora capsici and P. parasitica. To
      investigate whether genetic controls of resistance to two Phytophthora species
      are independent, we compared the genetic architecture of resistance of CM334 to
      both Phytophthora species. The RIL population F5YC used to construct the high
      resolution genetic linkage map of pepper was assessed for resistance to one
      isolate of each Phytophthora species. Inheritance of the P. capsici and P.
      parasitica resistance was polygenic. Twelve additive QTLs involved in the P.
      capsici resistance and 14 additive QTLs involved in the P. parasitica resistance
      were detected. The QTLs identified in this progeny were specific to these
      Phytophthora species. Comparative mapping analysis with literature data
      identified three colocations between resistance QTLs to P. parasitica and P.
      capsici in pepper. Whereas this result suggests presence of common resistance
      factors to the two Phytophthora species in pepper, which possibly derive from
      common ancestral genes, calculation of the colocation probability indicates that
      these colocations could occur by chance.

PMID- 17497123
TI  - [Is it possible to calculate minimum provider volumes for total knee replacement
      using routine data? Results of a threshold value analysis of German quality
      assurance data for inpatient treatment].
AB  - AIM OF THE STUDY: The aim of this study was to calculate, for the first time,
      minimum provider volumes in total knee replacement using routine German data.
      MATERIALS AND METHODS: In patients with primary total knee replacement (TKR), the
      relationship between hospital volume per year and risk of "insufficient mobility"
      (primary quality indicator) and "wound infection" (secondary quality indicator)
      was calculated by means of logistic regression models. RESULTS: For both
      indicators, a statistically significant relationship between hospital volume and
      outcome could be demonstrated. Other risk factors such as age and ASA status also
      had a significant influence, but did not appear as important confounders. The
      risk for the secondary quality indicator "infection" decreased constantly with
      increasing hospital volume, thus the curve was very flat. This supports the
      hypothesis that high volume hospitals have a higher quality level than low volume
      hospitals. A threshold value could be calculated. However, the explanation value
      for hospital volume was too low to derive a threshold level that clearly
      discriminates between good and bad quality of care. The relationship between the
      primary quality indicator "insufficient mobility" and hospital volume
      unexpectedly showed a U-shaped distribution. This questions the concept of a
      minimum provider volume regulation for primary total knee replacement for the
      quality indicator "insufficient mobility". Therefore, in this case no
      quantitative threshold values were calculated. CONCLUSION: This analysis supports
      the hypothesis of a volume-outcome relationship in primary total knee
      replacement. However, a minimum provider volume that clearly discriminates
      between good and bad quality of care could not be calculated on the basis of
      these German quality assurance data.

PMID- 17497122
TI  - Acute nutrient regulation of the unfolded protein response and integrated stress
      response in cultured rat pancreatic islets.
AB  - AIMS/HYPOTHESIS: Inadequate chaperone function relative to client protein load in
      the endoplasmic reticulum triggers an adaptive unfolded protein response (UPR),
      including the integrated stress response (ISR), the latter being also activated
      by other types of stresses. It is well established that pancreatic beta cells,
      which synthesise and secrete insulin upon nutrient stimulation, are markedly
      affected by pathological disruption or excessive activation of the UPR. However,
      whether and how physiological nutrient stimulation affects the beta cell UPR has
      been little investigated. MATERIALS AND METHODS: We compared the effects of
      increasing glucose concentrations and of endoplasmic reticulum Ca(2+) emptying
      with thapsigargin on the UPR (X-box binding protein [Xbp1] mRNA splicing and
      XBP1/activating transcription factor [ATF] 6-target gene expression) and ISR
      (eukaryotic translation initiation factor 2A phosphorylation, ATF4 protein levels
      and target gene expression) in isolated rat islets. RESULTS: Thapsigargin
      strongly increased both UPR and ISR. In comparison, glucose moderately increased
      the UPR between 5 and 30 mmol/l, but exerted complex effects on the ISR as
      follows: (1) marked reduction between 2 and 10 mmol/l; (2) moderate increase
      parallel to the UPR between 10 and 30 mmol/l. These glucose effects occurred
      within 2 h, were mimicked by other metabolic substrates, but were independent of
      changes in Ca(2+) influx or insulin secretion. Remarkably, attenuating the
      glucose stimulation of protein synthesis with a low concentration of
      cycloheximide prevented UPR activation but not ISR reduction by high glucose.
      CONCLUSIONS/INTERPRETATION: Nutrient stimulation acutely activates rat islet UPR
      in a manner dependent on protein synthesis, while exerting complex effects on the
      ISR. These effects may contribute to nutrient-induced maintenance of the beta
      cell phenotype.

PMID- 17497124
TI  - Is hyperlipasemia in critically ill patients of clinical importance? An
      observational CT study.
AB  - OBJECTIVE: To assess morphological alterations of the pancreas by contrast
      enhanced computed tomography (cCT) and subclinical cellular damage of the
      pancreas by measuring pancreatitis-associated protein (PAP) in critically ill
      patients without prior pancreatic disorder who presented with raised serum lipase
      levels. DESIGN: Prospective, observational study SETTING: Mixed
      surgical/neurosurgical intensive care unit of a German university hospital.
      PATIENTS: One hundred and thirty consecutive critically ill patients without
      prior damage or disease of the pancreas and an expected length of stay of more
      than 5 days. INTERVENTIONS: Daily serum lipase measurements and daily serum PAP
      measurements. Contrast-enhanced upper abdominal cCT study in patients with triple
      increase of serum lipase. MEASUREMENTS AND RESULTS: Thirty-eight patients showed
      raised serum lipase levels and qualified for the cCT scan study. In 20 patients
      cCT scans were performed. Morphological alterations of the pancreas were found in
      7 out these 20 patients while serum PAP levels were raised in all patients.
      CONCLUSION: Hyperlipasemia is a common finding in critically ill patients without
      prior pancreatic disorder. While elevated serum PAP levels indicate pancreatic
      cellular stress morphological alterations of the pancreas are rare and of little
      clinical importance.

PMID- 17497125
TI  - Prolonged exposure to inhaled nitric oxide does not affect haemostasis in
      piglets.
AB  - OBJECTIVE: To examine possible adverse effects on haemostasis from prolonged
      exposure to inhaled nitric oxide (iNO). DESIGN AND SETTING: Blinded, randomised,
      experimental animal study in a university animal laboratory. INTERVENTIONS:
      Anaesthetised and intubated piglets received central venous, arterial, and
      transabdominal urinary catheters. Twelve piglets were studied with triggered
      pressure support ventilation breathing with an air-oxygen mixture for 30 h with
      nitric oxide (NO), 40 parts per million (ppm) (n = 6) or without NO gas (n = 6)
      added. The tests of platelet function were assessed in a separate 1-h experiment
      in which 12 additional animals were blindly randomised to receive intravenous
      acetylsalicylic acid (ASA) (n = 7) or placebo (n = 5). MEASUREMENTS AND RESULTS:
      All 12 animals were clinically stable during the study period of 30 h.
      Haemostasis was assessed in terms of bleeding time and platelet function by
      Adeplat-S, reflecting platelet adhesion. Prothrombin fragment 1 + 2, fibrin D
      dimer, tissue plasminogen activator and prothrombin complex were measured to
      investigate whether inhaled NO (iNO) had any effects on thrombin formation,
      fibrin formation, fibrinolysis or coagulation. All parameters including bleeding
      time and Adeplat-S were unaffected by iNO. ASA significantly increased bleeding
      time, but did not affect Adeplat-S. Nitrate in plasma and NOx (nitrate and
      nitrite) in urine increased significantly in pigs receiving iNO compared with
      controls. CONCLUSIONS: Prolonged exposure to iNO at 40[Symbol: see text]ppm did
      not affect bleeding time or coagulation parameters in healthy piglets. The
      findings do not support the hypothesis that iNO increases the risk of bleeding in
      humans.

PMID- 17497126
TI  - Clinical presentation of femoroacetabular impingement.
AB  - The purpose of this study was to identify subjective complaints and objective
      findings in patients treated for femoroacetabular impingement (FAI). Three
      hundred and one arthroscopic hip surgeries were performed to treat FAI. The most
      frequent presenting complaint was pain, with 85% of patients reporting moderate
      or marked pain. The most common location of pain was the groin (81%). The average
      modified Harris Hip score was 58.5 (range 14-100). The average sports hip outcome
      score was 44.0 (range 0-100). The anterior impingement test was positive in 99%
      of the patients. Range of motion was reduced in the injured hip. Patients who had
      degenerative changes in the hip had a greater reduction in range of motion. The
      most common symptom reported in patients with FAI was groin pain. Patient showed
      decreased ability to perform activities of daily living and sports. Significant
      decreases in hip motion were observed in operative hips compared to non-operative
      hips.

PMID- 17497127
TI  - Lateral unicompartimental knee arthroplasty: indications, technique and short
      medium term results.
AB  - Lateral unicompartmental knee arthroplasty (UKA) is a valid alternative treatment
      in the event of arthritis confined to the lateral compartment. This paper
      examines its indications, technique and short to medium-term results. A total of
      159 Miller-Galante cemented UKA prostheses (Zimmer, Warsaw, Indiana) were
      implanted consecutively (131 medial and 28 lateral) by the same surgeon. This
      study investigates 28 lateral UKAs in 27 patients. Twenty-five implants in 24
      patients (including a subject operated bilaterally) were followed up for 12-60
      months. Three patients were discarded on account of to short a follow-up period.
      The Hospital for Special Surgery (HSS) knee score was used to compare the pre-
      and post-operative results of the lateral UKA patients. The HSS score improved
      from a pre-op mean of 59.92 (range 48-68) to 88.04 (range 71-95) at the last
      follow-up. There was a positive increase in the pain, function and ROM components
      of the score. The lateral UKA prosthesis can be regarded as a sound alternative
      to total knee replacement. Correct patient selection on the basis of optimum
      surgical indications, however, is essential.

PMID- 17497128
TI  - Arthroscopic management of calcific tendinitis of the subscapularis tendon.
AB  - Calcific tendinitis is a common disorder of the rotator cuff. Conservative
      treatment is frequently successful. For the patients remaining symptomatic after
      conservative treatment, excision of the calcium deposits offers a generally
      reliable pain relief. While calcific tendinitis is seen commonly affecting the
      supraspinatus tendon, it has been rarely reported involving the subscapularis
      tendon. We report on the clinical features, radiographic findings, arthroscopic
      treatment and results of one patient who presented a calcific tendonitis
      involving the subscapularis tendon of the left shoulder unresponsive to
      conservative treatment and associated subcoracoid stenosis and coracoid
      impingement.

PMID- 17497129
TI  - Effect of blood on the morphological, biochemical and biomechanical properties of
      engineered cartilage.
AB  - The use of autologous chondrocytes seeded onto a biological scaffold represents a
      current valid tool for cartilage repair. However, the effect of the contact of
      blood to the engineered construct is unknown. The aim of this work was to
      investigate in vitro the effect of blood on the morphological, biochemical and
      biomechanical properties of engineered cartilage. Articular chondrocytes were
      enzymatically isolated from swine joints, expanded in monolayer culture and
      seeded onto collagen membranes for 2 weeks. Then, the seeded membranes were
      placed for 3 days in contact with peripheral blood, which was obtained from
      animals of the same species and diluted with a standard medium. As controls, some
      samples were left in the standard medium. After the 3 days' contact, some samples
      were retrieved for analysis; others were returned to standard culture conditions
      for 21 additional days, in order to investigate the "long-term effect" of the
      blood contact. Upon retrieval, all seeded samples showed increasing sizes and
      weights over time. However, the samples exposed to blood presented lower values
      with respect to the controls. Biochemical evaluation demonstrated a reduction in
      the mitochondrial activity due to blood contact at the early culture time (3 days
      post blood contact), followed by a partial recovery at the longer culture time
      (21 days post blood contact). Histological evaluation demonstrated evident
      cartilage-like matrix production for both groups. Biomechanical data showed a
      reduction of the values, followed by stabilization, regardless of the presence of
      blood. Based on the data obtained in this study, we can conclude that blood
      contact affects the chondrocyte activity and determines a delay in the
      dimensional growth of the engineered cartilage; however, at the experimental
      times utilized in this study, this delay did not affect the histological pattern
      and the biomechanical properties of the construct.

PMID- 17497130
TI  - 3-T MR imaging of partial ACL tears: a cadaver study.
AB  - Magnetic resonance imaging (MRI) is the most commonly used diagnostic imaging
      procedure for suspected injuries to the anterior cruciate ligament (ACL).
      However, MRI has less utility for the evaluation of partial ACL tears. The goal
      of this study was to evaluate the possibility of distinguishing partial ACL tears
      applying the double bundle concept by dividing the ACL anatomy in the
      anteromedial (AM) and posterolateral bundle (PL). Six human cadaver knees were
      used in this laboratory study. The protocol consisted of sagittal, oblique
      coronal, and oblique sagittal proton-density-weighted fast spin echo sequences.
      After MRI the AM and the PL bundle were severed to mimic different partial ACL
      rupture patterns. MRI scanning of each knee was repeated, to record the
      quantitative parameters tilt and ACL angles and discontinuity as a
      nonquantitative parameter. Three orthopaedic surgeons and two radiologists were
      enlisted as blinded observers to evaluate the images. The transection patterns
      could be differentiated by evaluating discontinuity both in the paracoronal and
      in the sagittal plane. Evaluating the transection patterns, the AM bundle reached
      a better result in both planes compared to the PL bundle and the paracoronal
      plane had a better result in assessing the transection patterns compared to the
      sagittal plane for the PL bundle. Partial ACL transections could predictably be
      recognized on oblique sagittal and oblique coronal planes utilizing 3-T MRI
      technology. This concept allows a more precise description of ACL rupture
      patterns and might lead to a more distinctive approach for reconstructive
      surgery. The presurgical planning could be improved by applying a treatment
      algorithm based on a description of each bundle as intact or ruptured, leading to
      a reconstruction of the torn and a preservation of the intact bundle.

PMID- 17497131
TI  - Double-bundle anterior cruciate ligament reconstruction using two different
      suspensory femoral fixation: a technical note.
AB  - We describe a novel double-bundle reconstruction method for ACL deficient knee.
      Grafts are tibialis allograft for AMB (anteromedial bundle) and semitendinosus
      autograft for PLB (posterolateral bundle). Femoral fixations are done by Bio
      TransFix for AMB and EndoButton for PLB. Tibial fixations are done by Bio
      interference screw for AMB at 60-70 degrees knee flexion and secure the PLB and
      remnant AMB graft simultaneously onto anteromedial aspect of tibia at 10-20
      degrees knee flexion with spiked washer and screw. With our technique, graft
      lengths are not restricted and we provide strong femoral and tibial fixation if
      it is compared with previous techniques.

PMID- 17497132
TI  - Arthroscopic treatment of calcifying tendonitis of subscapularis and
      supraspinatus tendon: a case report.
AB  - Reports concerning the surgical treatment of calcifying tendinits of the
      subscapularis tendon are rare. We present the case of a symptomatic calcifying
      tendonitis involving the subscapularis and supraspinatus tendons. The patient was
      treated with an arthroscopic removal of the calcific deposits. One year after the
      surgical procedure the patient was completely pain free, had full range-of-motion
      and negative supraspinatus and subscapularis signs on manual muscle testing. The
      overall constant score was 93 points. Radiographic evaluation revealed a complete
      removal of the calcific deposits immediately after the procedure without
      recurrence after 1 year. We conclude that a combined arthroscopic removal of the
      calcific deposits of the subscapularis and supraspinatus tendons can lead to an
      excellent clinical outcome without compromising the functional integrity of the
      rotator cuff tendons.

PMID- 17497133
TI  - Isolated and combined Type II SLAP repairs in a military population.
AB  - The study compares the clinical results of isolated arthroscopic repair of Type
      II SLAP tears with those of combined treatment for Type II SLAP and other
      associated shoulder conditions. The population was composed of 36 aged-matched
      active duty males with a mean age of 31.6 years (range 22-41 years); mean follow
      up was 29.1 months (range 24-42 months). Eighteen subjects in Group I had
      isolated Type II SLAP tears. Eighteen subjects in Group II had Type II SLAP tear
      and concomitant ipsilateral shoulder conditions, including subacromial
      impingement in six patients, acromioclavicular arthrosis in three patients,
      subacromial impingement and acromioclavicular arthrosis in four patients,
      spinoglenoid cyst in four patients, and intra-articular loose bodies in one
      patient. Arthroscopic SLAP repair was performed with biodegradable suture
      anchors. Subacromial decompression and spinoglenoid cyst decompression were
      performed arthroscopically. Distal claviculectomy was performed in open fashion.
      Loose bodies were removed arthroscopically. At minimum 2-year follow-up, the mean
      UCLA score for Group I (30.2 +/- 3.0 points) was not significantly different from
      Group II (30.8 +/- 2.0 points) (P = 0.48). The mean post-operative ASES score for
      Group I (84.1 +/- 13.4 points) was significantly lower than for Group II (91.8 +/
      5.4 points) (P < 0.04). The mean VAS pain score for Group I (1.6 +/- 1.3 points)
      was significantly higher than for Group II (0.7 +/- 0.7 points) (P < 0.02).
      Seventeen of 18 patients (94%) in each group returned to full duty. In a
      population of active duty males, arthroscopic repair of isolated Type II SLAP had
      comparable results with a cohort of Type II SLAP repairs treated in combination
      with other shoulder conditions, with the combined treatment group having
      significantly better results in two of three parameters measured. Return to duty
      rates were identical. Therefore, concurrent treatment of other associated extra
      articular shoulder conditions improves the overall success of SLAP repair and the
      presence of these other conditions should be recognized and treated along with
      the SLAP tears in order to maximize clinical results.

PMID- 17497134
TI  - Diverse bacteria isolated from root nodules of Trifolium, Crotalaria and Mimosa
      grown in the subtropical regions of China.
AB  - To analyze the diversity and relationships of rhizobia in the subtropical and
      tropical zones of China, we characterized 67 bacterial strains isolated from root
      nodules of five legume species in the genera Trifolium, Crotalaria and Mimosa .
      PCR-amplified 16S rDNA RFLP, numerical taxonomy, SDS-PAGE of whole cell proteins,
      sequencing of 16S rDNA and DNA-DNA hybridization grouped the isolates into 17
      lineages belonging to Bradyrhizobium, Mesorhizobium, Rhizobium, Sinorhizobium and
      Burkholderia, as well as a non-symbiotic group of Agrobacterium. The Rhizobium
      group contained twenty strains isolated from Mimosa pudica, Crotalaria pallida
      and two species of Trifolium. Fifteen of them were R. leguminosarum. Twenty-one
      strains isolated from four species of Trifolium, Crotalaria and Mimosa were
      classified into five groups of Bradyrhizobium, including B. japonicum.
      Agrobacterium group composed of 20 isolates from Mimosa pudica, C. pallida and
      Trifolium fragiferum. In addition, several strains of Sinorhizobium and
      Mesorhizobium associated with Trifolium and Burkholderia associated with Mimosa
      pudica were also identified. The predominance of Bradyrhizobium in the nodules of
      Trifolium was a novel finding and it demonstrated that the nodule microsymbionts
      might be selected by both the geographic factors and the legume hosts.

PMID- 17497135
TI  - Validation of a rapid, non-radioactive method to quantify internalisation of G
      protein coupled receptors.
AB  - Agonist exposure can cause internalisation of G-protein coupled receptors
      (GPCRs), which may be a part of desensitisation but also of cellular signaling.
      Previous methods to study internalisation have been tedious or only poorly
      quantitative. Therefore, we have developed and validated a quantitative method
      using a sphingosine-1-phosphate (S1P) receptor as a model. Because of a lack of
      suitable binding studies, it has been difficult to study S1P receptor
      internalisation. Using a N-terminal HisG-tag, S1P(1) receptors on the cell
      membrane can be visualised via immunocytochemistry with a specific anti-HisG
      antibody. S1P-induced internalisation was concentration dependent and was
      quantified using a microplate reader, detecting either absorbance, a fluorescent
      or luminescent signal, depending on the antibodies used. Among those, the
      fluorescence detection method was the most convenient to use. The relative ease
      of this method makes it suitable to measure a large number of data points, e.g.
      to compare the potency and efficacy of receptor ligands.

PMID- 17497136
TI  - NMDA receptor modulation by D-cycloserine promotes episodic-like memory in mice.
AB  - RATIONALE: NMDA-R (N-methyl-D-aspartate receptors) have been implicated in
      synaptic plasticity underlying one-trial learning of event-place associations. In
      rodents, episodic-like memory (ELM) of personally experienced events can be
      inferred from behavior that reflects the remembrance of the content (what kind of
      object was presented), place (where was this object placed), and temporal context
      (when was the object presented). We have previously shown that that D-cycloserine
      (DCS), an NMDA-R agonist, ameliorates stress-induced deficits in ELM. OBJECTIVES:
      In this study, we used an experimental protocol designed to detect promnestic
      drug effects and investigated whether DCS, which is known to enhance learning and
      memory, can induce ELM under conditions where mice normally do not show ELM.
      RESULTS: Mice that have been treated i.p. with DCS (20 mg/kg) both remembered the
      temporal order in which two different objects had been encountered during two
      consecutive sample trials, as well as their spatial position during the sample
      trials. Most importantly, the test trial performance of these mice is compatible
      with ELM in terms of an integrated memory for unique experiences comprising
      "what", "where", and "when" information. In contrast, mice that have received
      either a saline injection or lower doses of DCS (0.2 and 2.0 mg/kg) did not show
      such an integrated ELM. CONCLUSIONS: To our knowledge, this is the first report
      showing that DCS can promote ELM in mice.

PMID- 17497137
TI  - Lack of behavioral sensitization after repeated exposure to THC in mice and
      comparison to methamphetamine.
AB  - RATIONALE: Recent evidence has provided support for the incentive-sensitization
      model of addiction, where repeated stimulation of neural reward circuits leads to
      a long-lasting sensitization of mesolimbic dopaminergic activity. This phenomenon
      has been demonstrated with many drugs of abuse, most often by measuring
      progressively increased activating effects of drugs on locomotor activity,
      thought to reflect an underlying neural sensitization. Whether cannabinoids, and
      in particular Delta(9)-tetrahydrocannabinol (THC), produce similar effects in
      this model is somewhat controversial, with mixed evidence in the literature.
      OBJECTIVES: These experiments were conducted to determine whether behavioral
      sensitization could be established in mice after repeated exposure to THC.
      Sensitization to repeated methamphetamine treatment was used as a positive
      control. METHODS: The effects of acute and repeated intermittent (every 3-4 days)
      treatment with THC or methamphetamine on locomotor activity were determined in
      Institute of Cancer Research (ICR) mice. Additional experiments with THC employed
      a dosing regimen that increased the number of injections, controlled for
      behavioral tolerance, examined different aspects of behavior, and used a
      different species (Sprague-Dawley rats). RESULTS: Both methamphetamine and THC
      acutely increased activity. A robust dose-dependent sensitization was observed
      after intermittent treatment with methamphetamine but not with THC. Additionally,
      no evidence for behavioral sensitization to the effects of THC was found with any
      of the various protocols. CONCLUSION: These data suggest that repeated THC
      treatment is less likely to produce behavioral sensitization than are other drugs
      of abuse. It appears that this phenomenon may only occur under very particular
      conditions, which raises doubts about its relevance to chronic cannabis users.

PMID- 17497140
TI  - Half-titration challenge.

PMID- 17497139
TI  - Serotonin transporter occupancy of high-dose selective serotonin reuptake
      inhibitors during major depressive disorder measured with [11C]DASB positron
      emission tomography.
AB  - RATIONALE: Previous work has shown 80% serotonin transporter (5-HTT) occupancy to
      be a consistent finding at the minimum therapeutic dose during selective
      serotonin reuptake inhibitor (SSRI) treatment. [(11)C]N,N-dimethyl-2-(2-amino-4
      cyanophenylthio) benzylamine positron emission tomography ([(11)C]DASB PET) is
      currently the best method available to quantify 5-HTT occupancy in humans.
      OBJECTIVES: The purpose of the present study is to determine 5-HTT occupancy
      during high dose SSRI treatment using [(11)C]DASB PET. MATERIALS AND METHODS:
      Twelve healthy subjects and 12 subjects with major depressive disorder completed
      the protocol. Depressed subjects received one [(11)C]DASB PET scan after a
      minimum of 4 weeks treatment at high doses of venlafaxine, sertraline, or
      citalopram. Baseline 5-HTT binding potential (BP) was taken as the average 5-HTT
      BP of the 12 healthy subjects. RESULTS: Mean striatal 5-HTT occupancy for each
      antidepressant group was approximately 85% at high therapeutic dose. This was
      significantly greater than 80% (one-sample t test; p < 0.04, venlafaxine group; p
      < 0.02, sertraline group; p < 0.01, citalopram group) for each high dose
      antidepressant group. CONCLUSIONS: Significantly greater 5-HTT blockade at high
      dose provides a rationale for raising the dose from the minimum therapeutic dose
      in specific clinical circumstances. It is likely that 15% unoccupied 5-HTT
      remains, which should be addressed in future drug development.

PMID- 17497138
TI  - Cognitive-disruptive effects of the psychotomimetic phencyclidine and attenuation
      by atypical antipsychotic medications in rats.
AB  - BACKGROUND: Cognitive deficits in schizophrenia are severe and do not respond
      well to available treatments. The development and validation of animal models of
      cognitive deficits characterizing schizophrenia are crucial for clarifying the
      underlying neuropathology and discovery of improved treatments for such deficits.
      MATERIALS AND METHODS: We investigated whether single and repeated
      administrations of the psychotomimetic phencyclidine (PCP) disrupt performance in
      the five-choice serial reaction time task (5-CSRTT), a test of attention and
      impulsivity. We also examined whether PCP-induced disruptions in this task are
      attenuated by atypical antipsychotic medications. RESULTS: A single injection of
      PCP (1.5-3 mg/kg, s.c., 30-min pre-injection time) had nonspecific response
      depressing effects. Repeated PCP administration (2 mg/kg for two consecutive days
      followed by five consecutive days, s.c., 30-min pre-injection time) resulted in
      decreased accuracy, increased premature and timeout responding, and increased
      response latencies. The atypical antipsychotic medications clozapine,
      risperidone, quetiapine, and olanzapine and the typical antipsychotic medication
      haloperidol did not disrupt 5-CSRTT performance under baseline conditions except
      at high doses. The response depression induced by a single PCP administration was
      exacerbated by acute clozapine or risperidone and was unaffected by chronic
      clozapine. Importantly, chronic clozapine partially attenuated the performance
      disruptions induced by repeated PCP administration, significantly reducing both
      the accuracy impairment and the increase in premature responding. CONCLUSIONS:
      Disruptions in 5-CSRTT performance induced by repeated PCP administration are
      prevented by chronic clozapine treatment and may constitute a useful animal model
      of some cognitive symptoms of schizophrenia.

PMID- 17497141
TI  - Analytical procedures for water-soluble vitamins in foods and dietary
      supplements: a review.
AB  - Water-soluble vitamins include the B-group vitamins and vitamin C. In order to
      correctly monitor water-soluble vitamin content in fortified foods for compliance
      monitoring as well as to establish accurate data banks, an accurate and precise
      analytical method is a prerequisite. For many years microbiological assays have
      been used for analysis of B vitamins. However they are no longer considered to be
      the gold standard in vitamins analysis as many studies have shown up their
      deficiencies. This review describes the current status of analytical methods,
      including microbiological assays and spectrophotometric, biosensor and
      chromatographic techniques. In particular it describes the current status of the
      official methods and highlights some new developments in chromatographic
      procedures and detection methods. An overview is made of multivitamin extractions
      and analyses for foods and supplements.

PMID- 17497142
TI  - Biosensor-guided screening for macrolides.
AB  - Macrolides are complex polyketides of microbial origin that possess an
      extraordinary variety of pharmacological properties, paired with an impressive
      structural diversity. Bioassays for specific detection of such compounds will be
      of advantage for a class-specific drug screening. The current paper describes a
      cell-based microbial biosensor, assigning a luminescence response to natural or
      chemically modified macrolides, independent from their biological activity. This
      biosensor is based on the coupling of the structural luciferase genes of Vibrio
      fischeri to the regulatory control mechanism of a bacterial erythromycin
      resistance operon. The bioassays is easy to handle and can be applied to various
      screening formats. The feasibility of the test system for natural products
      screening is exemplified by the isolation and characterization of picromycin from
      a Streptomyces species. Biosensor-guided screening for macrolides is based on
      macrolide-promoted expression of lux genes and induction of luminescence
      (independent of macrolide antibiotic activity).

PMID- 17497143
TI  - Lamotrigine in children and adolescents: the impact of age on its serum
      concentrations and on the extent of drug interactions.
AB  - OBJECTIVE: To investigate the impact of age and co-treatment with other drugs on
      the serum concentrations of lamotrigine in children and adolescents. METHODS: A
      review of routine serum concentration measurements of lamotrigine performed in
      our laboratory yielded a total of 744 serum samples from 296 subjects (110 males,
      186 females, age: 2-19 years) suitable for statistical analysis. The primary
      outcome variable was the dose-corrected lamotrigine serum concentration,
      expressed as the lamotrigine concentration/dose (C/D) ratio. A linear mixed model
      that allowed multiple observations from the same patient was used to identify and
      quantify the effect of factors influencing the lamotrigine C/D ratio. RESULTS:
      According to the model, the lamotrigine C/D ratio decreases by 6% per year of
      age. Valproate and levetiracetam were found to raise the lamotrigine C/D ratio,
      whereas the following co-medications reduced it: carbamazepine, clobazam,
      fluoxetine, clonazepam and ethinyl estradiol. The effect of carbamazepine
      decreased with increasing age. No gender difference was detected. CONCLUSIONS:
      Age is an important factor with respect to the pharmacokinetics and the extent of
      drug interactions of lamotrigine in children and adolescents. In this population,
      older individuals will need higher doses than younger ones in order to achieve
      the same serum concentrations.

PMID- 17497144
TI  - Therapeutic amoxicillin levels achieved with oral administration in term
      neonates.
AB  - AIMS: The standard treatment of neonatal group B Streptococcus infection is
      intravenous amoxicillin for 10 days. We investigated whether effective serum
      amoxicillin concentrations could be reached by switching to oral amoxicillin
      after 48 h of intravenous administration in full-term neonates with group B
      Streptococcus infection. METHODS: Over 2 years, we included 222 full-term
      neonates who had early onset group B streptococcal disease responsive to 48 h of
      intravenous amoxicillin, at which point they were asymptomatic and fed orally.
      They were switched to oral amoxicillin (300 or 200 mg/kg per day in four divided
      doses). Steady-state serum amoxicillin concentrations were determined 48 h later
      by high-performance liquid chromatography; values > or =5 mg/l were considered
      effective. RESULTS: Mean gestational age was 39.32 +/- 1.5 weeks ,and mean birth
      weight was 3,422 +/- 533 g; 29 newborns were bacteremic. Median serum amoxicillin
      concentration on oral therapy was 31,.15 (range 11-118) and 25.80 (range 5-84.8)
      with 300 and 200 mg/kg per day, respectively. None of the infants had a
      concentration <5 mg/l (p < 0.001). Gastrointestinal tolerance was satisfactory;
      216 patients were discharged at 5 days of age, and none was readmitted within the
      3-month follow-up. CONCLUSION: Early switching to the oral route in asymptomatic
      full-term newborns with early onset group B streptococcal disease maintained
      serum amoxicillin concentrations within our predefined therapeutic range (error
      risk<0.001). This strategy may hold potential for reducing treatment invasiveness
      and shortening hospital length of stay.

PMID- 17497146
TI  - A strategy for cloning glycosyltransferase genes involved in natural product
      biosynthesis.
AB  - The soil-borne and marine gram-positive Actinomycetes are a particularly rich
      source of carbohydrate-containing metabolites. With the advent of molecular tools
      and recombinant methods applicable to Actinomycetes, it has become feasible to
      investigate the biosynthesis of glycosylated compounds at genetic and biochemical
      levels, which has finally set the basis for engineering novel natural product
      derivatives. Glycosyltransferases (GT) are key enzymes for the biosynthesis of
      many valuable natural products that contain sugar moieties and they are most
      important for drug engineering. So far, the direct cloning of unknown
      glycosyltransferase genes by polymerase chain reaction (PCR) has not been
      described because glycosyltransferases do not share strongly conserved amino acid
      regions. In this study, we report a method for cloning of novel so far
      unidentified glycosyltransferase genes from different Actinomycetes strain. This
      was achieved by designing primers after a strategy named consensus-degenerate
      hybrid oligonucleotide primer (CODEHOP). Using this approach, 22 novel
      glycosyltransferase encoding genes putatively involved in the decoration of
      polyketides were cloned from the genomes of 10 Actinomycetes. In addition, a
      phylogenetic analysis of glycosyltransferases from Actinomycetes is shown in this
      paper.

PMID- 17497145
TI  - The spectrum of HLA-DQ and HLA-DR alleles, 2006: a listing correlating sequence
      and structure with function.
AB  - The list of alleles in the HLA-DRB, HLA-DQA, and HLA-DQB gene loci has grown
      enormously since the last listing in this journal 8 years ago. Crystal structure
      determination of several human and mouse HLA class II alleles, representative of
      two gene loci in each species, enables a direct comparison of ortholog and
      paralog loci. A new numbering system is suggested, extending earlier suggestions
      by [Fremont et al. in Immunity 8:305-317, (1998)], which will bring in line all
      the structural features of various gene loci, regardless of animal species. This
      system allows for structural equivalence of residues from different gene loci.
      The listing also highlights all amino acid residues participating in the various
      functions of these molecules, from antigenic peptide binding to homodimer
      formation, CD4 binding, membrane anchoring, and cytoplasmic signal transduction,
      indicative of the variety of functions of these molecules. It is remarkable that
      despite the enormous number of unique alleles listed thus far (DQA = 22, DQB =
      54, DRA = 2, and DRB = 409), there is invariance at many specific positions in
      man, but slightly less so in mouse or rat, despite their much lower number of
      alleles at each gene locus in the latter two species. Certain key polymorphisms
      (from substitutions to an eight-residue insertion in the cytoplasmic tail of
      certain DQB alleles) that have thus far gone unnoticed are highly suggestive of
      differences or diversities in function and thus call for further investigation
      into the properties of these specific alleles. This listing is amenable to
      supplementation by future additions of new alleles and the highlighting of new
      functions to be discovered, providing thus a unifying platform of reference in
      all animal species for the MHC class II allelic counterparts, aiding research in
      the field and furthering our understanding of the functions of these molecules.

PMID- 17497147
TI  - Single molecule techniques for the study of membrane proteins.
AB  - Single molecule techniques promise novel information about the properties and
      behavior of individual particles, thus enabling access to molecular
      heterogeneities in biological systems. Their recent developments to accommodate
      membrane studies have significantly deepened the understanding of membrane
      proteins. In this short review, we will describe the basics of the three most
      common single-molecule techniques used on membrane proteins: fluorescence
      correlation spectroscopy, single particle tracking, and atomic force microscopy.
      We will discuss the most relevant findings made during the recent years and their
      contribution to the membrane protein field.

PMID- 17497148
TI  - Biotransformation of glycerol to dihydroxyacetone by recombinant Gluconobacter
      oxydans DSM 2343.
AB  - The genus Gluconobacter is well known for its rapid and incomplete oxidation of a
      wide range of substrates. Therefore, Gluconobacter oxydans especially is used for
      several biotechnological applications, e.g., the efficient oxidation of glycerol
      to dihydroxyacetone (DHA). For this reaction, G. oxydans is equipped with a
      membrane-bound glycerol dehydrogenase that is also described to oxidize sorbitol,
      gluconate, and arabitol. Here, we demonstrated the impact of sldAB overexpression
      on glycerol oxidation: Beside a beneficial effect on the transcript level of the
      sldB gene, the growth on glycerol as a carbon source was significantly improved
      in the overexpression strains (OD 2.8 to 2.9) compared to the control strains (OD
      2.8 to 2.9). Furthermore, the DHA formation rate, as well as the final DHA
      concentration, was affected so that up to 350 mM of DHA was accumulated by the
      overexpression strains when 550 mM glycerol was supplied (control strain: 200 to
      280 mM DHA). Finally, we investigated the effect on sldAB overexpression on the
      G. oxydans transcriptome and identified two genes involved in glycerol
      metabolism, as well as a regulator of the LysR family.

PMID- 17497149
TI  - MR imaging of erosions in interphalangeal joint osteoarthritis: is all
      osteoarthritis erosive?
AB  - OBJECTIVE: Erosive osteoarthritis is usually considered as an inflammatory subset
      of osteoarthritis (OA). However, an inflammatory component is now recognised in
      all subsets of OA, so this subgroup of erosive or inflammatory OA is more
      difficult to conceptualise. The aim of this study was to compare routine CR and
      MRI to investigate erosion numbers and morphology to determine whether hand OA in
      general is a more erosive disease than previously recognised. DESIGN AND METHODS:
      Fifteen patients with clinical (OA) of the small joints of the hand underwent MRI
      of one of the affected proximal interphalangeal (PIP) or distal interphalangeal
      (DIP) joints. Conventional radiographs (CR) of the hand were also obtained. The
      MR images were reviewed by two observers for the presence of central and marginal
      erosions. The site and morphology of any erosions was recorded. CR images of the
      same hand joint were scored independently for central and marginal erosions by
      the same observers. RESULTS: There was 100% agreement between the observers for
      scoring erosions on CR. Agreement for the MRI scores was also excellent (kappa =
      0.84). MRI detected 37 erosions, of which only 9 were seen on CR. The increase in
      sensitivity using MRI was much greater for marginal erosions (1 detected on CR,
      19 on MRI) than for central erosions (8 on CR, 18 on MRI). Using MRI 80% of
      joints examined showed 1 or more erosions compared with 40% using CR. If only
      marginal erosions were considered 80% of joints were still considered erosive by
      MRI criteria, but only 1 showed evidence of erosion on CR. Morphologically
      central erosions appeared to represent areas of subchondral collapse and pressure
      atrophy. In contrast, marginal erosions resembled those seen in inflammatory
      arthritides. CONCLUSION: Erosions, and particularly marginal erosions typical of
      those seen in inflammatory arthritis, are a more common feature of small joint OA
      than conventional radiographs have previously indicated.

PMID- 17497150
TI  - Anterior cervical locking plate-related complications; prevention and treatment
      recommendations.
AB  - A retrospective study evaluating complications in 2,233 consecutive patients of
      subaxial cervical disorders treated with an anterior cervical locking plate was
      performed, and recommendations for prevention and treatment were made. The
      average length of follow-up was 1.3 years. Any loosening or breaking of the
      plates and screws or malpositions that threatened tracheoesophageal or
      neurovascular structures were defined as the complications. There were 239 cases
      (10.7%) with different kinds of complications. The complications included oblique
      plating in 56 cases in which the screw could irritate the nerve root. Screws were
      driven into the disc space in four cases, which ultimately led to plate
      loosening. Screws penetrated the endplate or passed excessively close to it
      producing a triangle fracture in 19 cases. Loosening or breaking of the plate and
      the screw was found in 115 cases. These phenomena were always associated with non
      union. Three oesophageal perforations occurred and conservative treatments proved
      effective. Finally, overlong plates impinged on the adjacent level in 14 cases
      and promoted disc degeneration ultimately leading to revision surgery. Good
      training and careful operation may help to decrease the complication rate. Most
      hardware complications are not symptomatic and can be treated conservatively.
      Only a few of them need immediate reoperation.

PMID- 17497151
TI  - Travelling-wave behaviour in a multiphase model of a population of cells in an
      artificial scaffold.
AB  - This paper analyses travelling-wave behaviour in a recently-formulated multiphase
      model for the growth of biological tissue that comprises motile cells and water
      inside a porous scaffold. The model arises in the context of tissue engineering,
      and its purpose is to study how cells migrate and proliferate inside porous
      biomaterials. In suitable limits, tissue growth in the model is shown to occur in
      the form of travelling waves that can propagate either forwards or backwards,
      depending on the values of the parameters. In the case where the drag force
      between the scaffold and the cells is non-zero, the growth of the aggregate can
      be analysed in terms of the propagation of a constant-speed wavefront in a semi
      infinite domain. A numerical (shooting) method is described for calculating the
      wave speed, and detailed results for how the speed varies with respect to the
      parameters are given. In the case where the drag force is zero, the size of the
      aggregate is shown either to grow or to shrink exponentially with time. These
      results may be of importance in determining the experimental factors that control
      tissue invasiveness in scaffolds thereby allowing greater control over engineered
      tissue growth.

PMID- 17497153
TI  - Progressive myelopathy due to meningeal thickening in shunted patients:
      description of a novel entity and the role of surgery.

PMID- 17497152
TI  - Analysis of a LEA gene promoter via Agrobacterium-mediated transformation of the
      desiccation tolerant plant Lindernia brevidens.
AB  - An Agrobacterium tumefaciens-based transformation procedure was developed for the
      desiccation tolerant species Lindernia brevidens. Leaf explants were infected
      with A. tumefaciens strain GV3101 harbouring a binary vector that carried the
      hygromycin resistance gene and an eGFP reporter gene under the control of a
      native dehydration responsive LEA promoter (Lb2745pro). PCR analysis of the
      selected hygromycin-resistant plants revealed that the transformation rates were
      high (14/14) and seeds were obtained from 13/14 of the transgenic lines. A
      combination of RNA gel blot and microscopic analyses demonstrated that eGFP
      expression was induced upon dehydration and ABA treatment. Comparison with
      existing procedures used to transform the well studied resurrection plant and
      close relative, Craterostigma plantagineum, revealed that the transformation
      process is both rapid and leads to the production of viable seed thus making L.
      brevidens a candidate species for functional genomics approaches to determine the
      genetic basis of desiccation tolerance.

PMID- 17497154
TI  - Progressive myelopathy due to meningeal thickening in shunted patients:
      description of a novel entity and the role of surgery.

PMID- 17497155
TI  - Progressive myelopathy due to meningeal thickening in shunted patients:
      description of a novel entity and the role of surgery.

PMID- 17497156
TI  - Progressive myelopathy due to meningeal thickening in shunted patients:
      description of a novel entity and the role of surgery.

PMID- 17497157
TI  - Progressive myelopathy due to meningeal thickening in shunted patients:
      description of a novel entity and the role of surgery.

PMID- 17497158
TI  - Progressive myelopathy due to meningeal thickening in shunted patients:
      description of a novel entity and the role of surgery.
AB  - INTRODUCTION: Spinal cord compression due to meningeal thickening is a rare
      occurrence in shunted patients. Because of the long delay to clinical onset, this
      complication has not been identified as yet. AIMS: We report on nine cases of
      shunt-related progressive myelopathy due to meningeal thickening (SPMMT).
      MATERIALS AND METHODS: We reviewed our database of shunted children, for cases
      having developed progressive tetraparesis due to cervical meningeal thickening.
      RESULTS: We identified nine observations of SPMMT, eight of these with
      hydrocephalus due to neonatal meningitis; the last case had Dandy-Walker
      malformation shunted at birth and suffered postoperative meningitis. The age of
      clinical onset of myelopathy was between 6 and 20 years (median 12.8). All
      patients presented with slowly progressive walking difficulties with falls and no
      spinal pain. Magnetic resonance imaging (MRI) showed typically a thickened dura
      mater with collapse of the arachnoid space, compensatory expansion of the
      epidural fat, and T2 hyperintensity in the spinal cord. We operated on seven
      patients for surgical decompression and arachnoidolysis: One died postoperatively
      because of shunt malfunction, and two others died later of complications of
      tetraplegia. Three patients were aggravated after surgery, three experienced
      partial improvement, but one of these subsequently deteriorated again.
      CONCLUSION: SPMMT appears to be a novel and well-defined clinical and
      pathological entity; its pathological and radiological features are stereotyped;
      however, the diagnosis is delayed because of the slow pace of the disease.
      Although surgical decompression may be the only option, its results were poor in
      our experience; earlier surgery might improve this grim prognosis.

PMID- 17497159
TI  - Testicular nubbins and prosthesis insertion: is it all just in the timing?

PMID- 17497160
TI  - Effect of neoadjuvant chemoradiation on postoperative fecal continence and anal
      sphincter function in rectal cancer patients.
AB  - BACKGROUND AND AIMS: Neoadjuvant chemoradiation (nCRT) followed by curative
      surgery has gained acceptance as the therapy of choice in locally advanced rectal
      cancer. This prospective study evaluates the effect of nCRT on postoperative
      anorectal function and continence. PATIENTS AND METHODS: Group A consisted of 12
      patients (59.8 +/- 11.9 years, male:female = 8:4) who received nCRT (5-FU, CPT
      11. 45 + 5.4 Gy boost) before surgery and Group B of 27 patients (61.9 +/- 10.6
      years, male:female = 16:11) who were treated by surgery alone. All patients
      received a questionnaire to evaluate stool continence and anorectal function
      before as well as after surgery. Anorectal function was further analyzed by
      perfusion manometry pre- and postoperatively. RESULTS: Preoperatively, none of
      the patients had signs or symptoms of fecal incontinence, and preoperative
      measurements showed values within normal limits. Postoperatively, fecal
      continence was impaired in both groups, but no significant difference was found
      between patients with or without nCRT. Anorectal manometry revealed an impairment
      of anorectal function after low anterior resection regardless of the treatment
      regime. CONCLUSION: nCRT does not impair anorectal function and fecal continence.
      The deterioration of continence and anal sphincter function after sphincter
      preserving surgery is solely caused by the surgical procedure.

PMID- 17497161
TI  - Two-staged decompression for thoracic paraparesis due to the combined
      ossification of the posterior longitudinal ligament and the ligamentum flavum: a
      case report.
AB  - STUDY DESIGN: A case report of ossification of the posterior longitudinal
      ligament (OPLL) combined with ossification of the ligamentum flavum, or yellow
      ligament (OYL), in the upper thoracic spine. OBJECTIVE: To describe a rare
      clinical entity and its management pitfalls in a patient with upper thoracic
      myelopathy due to combined OPLL and OYL. METHODS: A 52-year-old woman developed
      paresthesia and paraparesis of both legs. One month prior to admission she fell
      and became unable to walk. She was diagnosed as having upper thoracic myelopathy
      due to combined OPLL and OYL and was treated by two-stage anterior and posterior
      spinal decompression. Posterior decompression was achieved first by laminoplasty
      at C3-Th1 and laminectomy of Th2 and Th3. RESULTS: After posterior decompression,
      her symptoms immediately and dramatically improved. However, symptoms recurred
      after she was able to achieve a sitting or standing position. We then performed
      anterior decompression at Th2, which again improved her symptoms. At two years
      post-surgery, she is ambulatory with the use of a cane. CONCLUSION: Upper
      thoracic myelopathy due to OPLL and OYL was treated by combined 2-staged anterior
      and posterior decompression. In this case, posterior decompression alone was
      inadequate to relieve the symptoms of this pathological condition.

PMID- 17497163
TI  - High levels of CA125 (over 1,000 IU/ml) in patients with gynecologic disease and
      no malignant conditions: three cases and literature review.
AB  - OBJECTIVE: To report the very high serum levels of CA125 in patients with benign
      gynecologic disease which manifests as pelvic mass. METHODS: Clinical data of
      three cases with high levels of CA125 over 1,000 IU/ml and benign gynecologic
      conditions were gathered. in Vali-Asr hospital. RESULTS: Three patients were
      scheduled for laparatomy as ovarian cancer and leiomyosarcoma. Histologic results
      after laparatomy showed uterine myoma in two patients and endometrioma in a third
      patient. CONCLUSION: High levels of CA125 over 1,000 IU/ml, may be showed in
      other gynecologic conditions with no malignancy. So, other clinical and imaging
      data could be helpful for differential diagnosis of these patients.

PMID- 17497162
TI  - German evidence-based guidelines for the treatment of Psoriasis vulgaris (short
      version).
AB  - Psoriasis vulgaris is a common and chronic inflammatory skin disease which has
      the potential to significantly reduce the quality of life in severely affected
      patients. The incidence of psoriasis in Western industrialized countries ranges
      from 1.5 to 2%. Despite the large variety of treatment options available, patient
      surveys have revealed insufficient satisfaction with the efficacy of available
      treatments and a high rate of medication non-compliance. To optimize the
      treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and
      the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to
      develop evidence-based guidelines for the management of psoriasis. The guidelines
      focus on induction therapy in cases of mild, moderate, and severe plaque-type
      psoriasis in adults. The short version of the guidelines reported here consist of
      a series of therapeutic recommendations that are based on a systematic literature
      search and subsequent discussion with experts in the field; they have been
      approved by a team of dermatology experts. In addition to the therapeutic
      recommendations provided in this short version, the full version of the
      guidelines includes information on contraindications, adverse events, drug
      interactions, practicality, and costs as well as detailed information on how best
      to apply the treatments described (for full version, please see Nast et al.,
      JDDG, Suppl 2:S1-S126, 2006; or http://www.psoriasis-leitlinie.de ).

PMID- 17497165
TI  - Occurrence of "mammalian" lignans in plant and water sources.
AB  - Enterolignans, also called "mammalian" lignans because they are formed in the
      intestine of mammals after ingestion of plant lignans, were identified for the
      first time in extracts of four tree species, i.e., in knot heartwood of the
      hardwood species Fagus sylvatica and in knot or stem heartwood of the softwood
      species Araucaria angustifolia, Picea smithiana, and Abies cilicia. They were
      also identified for the first time in grain extracts of cultivated plants, i.e.,
      in 15 cereal species, in 3 nut species, and in sesame and linseeds. Furthermore,
      some plant lignans and enterolignans were identified in extracts of water from
      different sources, i.e., in sewage treatment plant influent and effluent and in
      humic water, and for the first time also in tap and seawater. They were present
      also in water processed through a water purification system (ultrapure water). As
      enterolignans seem to be abundant in the aquatic environment, the occurrence of
      enterolignans in plant sources is most likely due to uptake by the roots from the
      surrounding water. This uptake was also shown experimentally by treating wheat
      (Triticum aestivum ssp. vulgare) seeds with purified lignan-free water spiked
      with enterolactone (EL) during germination and growth. Both the remaining seeds
      and seedlings contained high EL levels, especially the roots. They also contained
      metabolites of EL, i.e., 7-hydroxy-EL and 7-oxo-EL.

PMID- 17497164
TI  - Rhizobacterial volatile emissions regulate auxin homeostasis and cell expansion
      in Arabidopsis.
AB  - Certain plant growth-promoting rhizobacteria (PGPR), in the absence of physical
      contact with a plant stimulate growth via volatile organic compound (VOC)
      emissions, through largely unknown mechanisms. To probe how PGPR VOCs trigger
      growth in plants, RNA transcript levels of Arabidopsis seedlings exposed to
      Bacillus subtilus (strain GB03) were examined using oligonucleotide microarrays.
      In screening over 26,000 protein-coded transcripts, a group of approximately 600
      differentially expressed genes related to cell wall modifications, primary and
      secondary metabolism, stress responses, hormone regulation and other expressed
      proteins were identified. Transcriptional and histochemical data indicate that
      VOCs from the PGPR strain GB03 trigger growth promotion in Arabidopsis by
      regulating auxin homeostasis. Specifically, gene expression for auxin synthesis
      was up regulated in aerial regions of GB03-exposed plants; auxin accumulation
      decreased in leaves and increased in roots with GB03 exposure as revealed in a
      transgenic DR5::GUS Arabidopsis line, suggesting activation of basipetal auxin
      transport. Application of the auxin transport inhibitor 1-naphthylphthalamic acid
      (NPA) restricted auxin accumulation to sites of synthesis thereby preventing GB03
      mediated decreases in shoot auxin levels as well as thwarting GB03-mediated
      growth promotion. In addition, microarray data revealed coordinated regulation of
      cell wall loosening enzymes that implicated cell expansion with GB03 exposure,
      which was confirmed by comparative cytological measurements. The discovery that
      bacterial VOCs, devoid of auxin or other known plant hormones regulate auxin
      homeostasis and cell expansion provides a new paradigm as to how rhizobacteria
      promote plant growth.

PMID- 17497166
TI  - A complement response may activate metamorphosis in the ascidian Boltenia
      villosa.
AB  - Ascidian metamorphosis transforms a free-swimming larval chordate ascidian into a
      sessile adult through a distinct series of metamorphic events. Initially, larvae
      must become competent to respond to settlement cues. Settlement is then marked by
      dramatic body plan remodeling and may be accompanied by attachment to the
      substrate. Subtractive hybridization has revealed that many innate immunity
      transcripts are upregulated during metamorphosis in the ascidian Boltenia
      villosa. Several of these genes have well-known roles in the mannose-binding
      lectin (MBL)-complement pathway of innate immunity, including MBL and MBL
      activated serine protease (MASP). MBL recognizes and binds to bacterial
      pathogens, activates MASP, and triggers the complement cascade. In B. villosa,
      larvae upregulate BvMASP at the time of competency to initiate settlement. We
      show that several bacterial strains can induce settlement and that the timing of
      BvMASP expression in the papillae-associated tissue (PAT) cells is tightly
      correlated with larval competency. We further demonstrate that serine protease
      inhibitors used to block the complement response also block metamorphosis,
      allowing tail resorption, but preventing further morphological changes. Based on
      these experiments, we propose that the MBL-complement pathway may be important
      for competency, bacterial substrate detection and body plan remodeling during
      metamorphosis.

PMID- 17497167
TI  - CD10 is expressed by mammary myofibroblastoma and spindle cell lipoma of soft
      tissue: an additional evidence of their histogenetic linking.

PMID- 17497168
TI  - Down-regulation of retinol binding protein 5 is associated with aggressive tumor
      features in hepatocellular carcinoma.
AB  - PURPOSE: Acyclic retinoid (ACR) has been shown to be a promising chemopreventive
      agent for hepatocellular carcinoma (HCC) after curative resection. The effects of
      retinoid are mediated by retinol-binding proteins (RBPs) through regulating cell
      proliferation and differentiation. PATIENTS AND METHODS: This study investigated
      the clinical significance of RBP5 in HCC. RBP5 mRNA level was examined by real
      time quantitative PCR on 52 matched tumor and adjacent non-tumor liver tissues,
      and on ten normal livers. Expression of RBP5 protein was examined using Western
      blotting analysis and immunohistochemistry. RESULTS: Down-regulation of RBP5 was
      found in HCC tissues at both mRNA and protein levels. Decreased RBP5 level was
      closely related to poor differentiation (P=0.02) and large tumor size (P=0.01).
      Low level of RPB5 was associated with poor overall survival (P=0.02), and was an
      independent prognostic factor for HCC. CONCLUSIONS: Our study revealed that RBP5
      down-regulation in HCC was associated with aggressive tumor features, suggesting
      an important role of RPB5 in HCC progression.

PMID- 17497169
TI  - Molecular identification of a Cryptosporidium saurophilum from corn snake (Elaphe
      guttata guttata).

PMID- 17497170
TI  - Effects of Schistosoma mansoni and Schistosoma haematobium infections on calcium
      content in their intermediate hosts.
AB  - Flame atomic absorption spectrometry was performed to determine the alteration of
      calcium concentration in the soft parts and shells of Biomphalaria alexandrina
      and Bulinus truncatus due to the infection with Schistosoma mansoni and S.
      haematobium, respectively. The results showed significant lowering in the calcium
      content of the shells of cercariae shedding B. alexandrina and B. truncatus
      relative to the calcium content in the shells of uninfected ones. In contrast,
      the calcium content in the soft parts of cercariae shedding snails was higher
      than in the soft parts of uninfected snails; the differences were statistically
      significant. Generally, calcium content was significantly higher in the shells
      than in the soft parts of the snails, regardless infected or uninfected. The
      results obtained and the hypothesis of hypercalcification in shells of infected
      snails were discussed.

PMID- 17497171
TI  - The use of an excreted superoxide dismutase in an ELISA and Western blotting for
      the diagnosis of Leishmania (Leishmania) infantum naturally infected dogs.
AB  - An excreted iron superoxide dismutase of pI 3.75 and a molecular mass of
      approximately 25 kDa was partially purified by QAE Sephadex ion-exchange
      chromatography from the in vitro culture of Leishmania (Leishmania) infantum.
      This enzyme was detected by enzyme-linked immunosorbent assay and Western blot of
      anti-L. infantum antibodies in dog serum. For the determination of the
      sensitivity and specificity of this protein, the results using the complete
      parasite antigen fraction were taken as references. For this, 39 sera were
      assayed in dogs from different Spanish provinces. By Western blot, at a dilution
      of 1:250, 82% of the sera were positive when superoxide dismutase excreted was
      used as the antigen, against 56.4% positivity when the complete parasite was used
      as the antigen. These findings support the results of a previous study,
      indicating that the superoxide dismutase excreted can be useful in diagnosing L.
      (L.) infantum.

PMID- 17497172
TI  - Utility of ITS1-5.8S-ITS2 sequences for species discrimination and phylogenetic
      inference of two closely related bucephalid digeneans (Digenea: Bucephalidae):
      Dollfustrema vaneyi and Dollfustrema hefeiensis.
AB  - The complete internal transcribed spacer 1 (ITS1), 5.8S ribosomal DNA, and ITS2
      region of the ribosomal DNA from 60 specimens belonging to two closely related
      bucephalid digeneans (Dollfustrema vaneyi and Dollfustrema hefeiensis) from
      different localities, hosts, and microhabitat sites were cloned to examine the
      level of sequence variation and the taxonomic levels to show utility in species
      identification and phylogeny estimation. Our data show that these molecular
      markers can help to discriminate the two species, which are morphologically very
      close and difficult to separate by classical methods. We found 21 haplotypes
      defined by 44 polymorphic positions in 38 individuals of D. vaneyi, and 16
      haplotypes defined by 43 polymorphic positions in 22 individuals of D.
      hefeiensis. There is no shared haplotypes between the two species. Haplotype
      rather than nucleotide diversity is similar between the two species. Phylogenetic
      analyses reveal two robustly supported clades, one corresponding to D. vaneyi and
      the other corresponding to D. hefeiensis. However, the population structures
      between the two species seem to be incongruent and show no geographic and host
      specific structure among them, further indicating that the two species may have
      had a more complex evolutionary history than expected.

PMID- 17497173
TI  - Immunomodulative effect of glucan and/or glucan supplemented with zinc in
      albendazole therapy for murine alveolar echinococcosis.
AB  - The effect of glucan immunomodulator (GI) and glucan supplemented with zinc
      (GIZn) administered separately or with albendazole (ABZ) on cellular immunity of
      mice with alveolar echinococcosis was observed. The stimulative effect of GI and
      GI + ABZ therapy on proliferative response of T lymphocytes was prolonged by GIZn
      or GIZn + ABZ from week 6 to 14 postinfection (p.i.). The increased proliferation
      of B lymphocytes was observed during combined therapies GI + ABZ and GIZn + ABZ
      from week 6 to 12 p.i. Number of splenic CD4 T cells in mice with GI or GI + ABZ
      therapy was increased only on weeks 6 and 8 p.i. GIZn and GIZn + ABZ therapy
      prolonged this stimulation from week 6 to 14 p.i. Serum concentration of
      interferon-gamma (IFN-gamma) was increased after GIZn therapy and reduced after
      GI therapy from week 8 to 12 p.i. GIZn + ABZ therapy had the highest effect on
      the IFN-gamma rise from week 8 to 22 p.i. Both GI and GIZn inhibited the serum
      concentration of interleukin-5 (IL-5) from week 6 p.i. The production of
      superoxide anion was increased after GI therapy from week 6 to 14 p.i. and after
      GI + ABZ or GIZn + ABZ therapies from week 12 to 18 p.i. The most effective
      antiparasitic therapy for alveolar echinococcosis was reached by GIZn + ABZ
      therapy.

PMID- 17497175
TI  - Genetic variation in catechol-O-methyltransferase (COMT) and obesity in the
      prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial.
AB  - Catechol-O-methyltransferase (COMT) is an important modulator in the catabolism
      of extraneural dopamine, which plays an important role in drug reward mechanisms.
      It is hypothesized that genetic variations in the COMT gene, which can result in
      a three to fourfold difference in COMT enzyme activity, may be associated with
      several reward-motivated behaviors. The aim of our study was to examine the
      relationship between COMT polymorphisms with smoking, obesity and alcohol. Three
      single nucleotide polymorphisms (SNPs) in COMT were genotyped in 2,371
      participants selected randomly from the screening arm of the PLCO Cancer
      Screening Trial after stratifying by sex, age, and smoking status. Smoking,
      obesity, and alcohol consumption were assessed by questionnaire. SNP and
      haplotype associations were estimated using odds ratios (ORs) and 95% confidence
      intervals (CIs) derived from conditional logistic regression models, adjusted for
      race/ethnicity. The COMT Ex4-76C > G (Leu136Leu) polymorphism was statistically
      significantly associated with individuals who had >30% increases in BMI from ages
      20 to 50 years, compared to those with 0-5% increase in BMI (0-5%) over the same
      age period: (CC is referent; OR(CG )= 1.42, OR(GG )= 1.46, P (trend )= 0.06). By
      sex, the increased risk was further pronounced among females (OR(CG )= 1.50,
      OR(GG )= 2.10, P (trend )= 0.03). Consistent with our analyses of single
      polymorphisms, individuals whose BMI increased >30% from ages 20 to 50 years were
      more likely than individuals with 0-5% increases in BMI to possess COMT
      haplotypes [COMT Ex3-104C > T-COMT Ex4-76 C > G-COMT Ex4-12 A > G] that included
      the variant allele for COMT Ex4-76 C > G: C-G-G (T-C-A is referent: OR(C-G-G )=
      1.33, 95% CI 1.01-1.77) and C-G-A (OR(C-G-A )= 1.79, 95% CI 0.72-4.49). We
      observed no association between any of the COMT polymorphisms with smoking
      behavior or alcohol intake. The COMT Ex4-76C > G (Leu136Leu) polymorphism appears
      to play a role in large increases in BMI. The null association with smoking and
      alcohol and the pronounced association with increasing BMI among women further
      implicates COMT's role in estrogen metabolism as a potentially culpable pathway.
      Our results support a need for comprehensive evaluation of COMT variations and
      their functional relevance as COMT may be an important molecular target to
      evaluate for new treatments regarding obesity.

PMID- 17497176
TI  - Influence of extended operation time and of occlusal force on determination of
      pulpal healing pattern in replanted mouse molars.
AB  - The mechanism regulating the divergent healing processes following tooth
      replantation is unclear. This study clarifies the relationship between the
      healing pattern, the time taken for tooth replantation, and the influence of
      occlusal force. We investigated the pulpal healing process after tooth
      replantation by immunohistochemistry for 5-bromo-2'-deoxyuridine and nestin and
      by histochemistry for tartrate-resistant acid phosphatase. The upper right first
      molar of 3-week-old mice was extracted and repositioned in the original socket
      immediately or 30 min to 6 h after the operation. We divided the animals into a
      non-occluded group in which the lower right first molar was extracted and an
      occluded group without extraction of the counterpart tooth. In control teeth
      (upper left first molar), the periphery of the coronal dental pulp showed intense
      nestin-positive reaction. Tooth replantation weakened the nestin-positive
      reaction in the pulp tissue. On postoperative days 5-7, tubular dentin formation
      commenced next to preexisting dentin in which nestin-positive odontoblast-like
      cells were arranged in successful cases. In other cases, bone-like tissue
      formation occurred in the pulp chamber until day 14. The ratio of tertiary dentin
      formation was significantly higher in the non-occluded group. The intentionally
      prolonged time for the completion of tooth replantation induced bone-like tissue
      formation, expanded inflammatory reaction, or fibrous tissue formation in pulp
      tissue. Thus, the lack of a proper oxygenated medium is probably decisive for the
      survival of odontoblast-lineage cells, and occlusal force during and/or after
      operation worsens the fate of these cells.

PMID- 17497174
TI  - Analysis of EST sequences suggests recent origin of allotetraploid colonial and
      creeping bentgrasses.
AB  - Advances in plant genomics have permitted the analysis of several members of the
      grass family, including the major domesticated species, and provided new insights
      into the evolution of the major crops on earth. Two members, colonial bentgrass
      (Agrostis capillaris L.) and creeping bentgrass (A. stolonifera L.) have only
      recently been domesticated and provide an interesting case of polyploidy and
      comparison to crops that have undergone human selection for thousands of years.
      As an initial step of characterizing these genomes, we have sampled roughly 10%
      of their gene content, thereby also serving as a starting point for the
      construction of their physical and genetic maps. Sampling mRNA from plants
      subjected to environmental stress showed a remarkable increase in transcription
      of transposable elements. Both colonial and creeping bentgrass are
      allotetraploids and are considered to have one genome in common, designated the
      A2 genome. Analysis of conserved genes present among the ESTs suggests the
      colonial and creeping bentgrass A2 genomes diverged from a common ancestor
      approximately 2.2 million years ago (MYA), thereby providing an enhanced
      evolutionary zoom in respect to the origin of maize, which formed 4.8 MYA, and
      tetraploid wheat, which formed only 0.5 MYA and is the progenitor of domesticated
      hexaploid wheat.

PMID- 17497177
TI  - Expression of retinaldehyde dehydrogenase 1 in the anterior pituitary glands of
      adult rats.
AB  - Retinoic acid (RA) plays a critical role in cell growth and tissue development
      and is also a regulatory factor of pituitary function. However, whether RA is
      generated in the pituitary gland and plays a role as a paracrine and/or autocrine
      factor is generally unknown. RA is synthesized from retinoids through oxidation
      processes. Dehydrogenases that catalyze the oxidation of retinal to RA are
      members of the retinaldehyde dehydrogenase (RALDH) family. Recently, we
      demonstrated that RALDH2 and RALDH3, but not RALDH1, were expressed in the
      developing anterior pituitary gland of rats, but the expression of RALDHs in the
      adult pituitary gland was not determined. Therefore, we have now examined the
      expression of RALDH1, RALDH2, and RALDH3 mRNAs in the pituitary gland of adult
      rats. Analysis by quantitative real-time polymerase chain reaction of adult
      pituitary glands has revealed a high level of RALDH1 mRNA but not of RALDH2 mRNA
      or RALDH3 mRNA. We have also detected mRNA expression for RALDH1 in the anterior
      pituitary gland by in situ hybridization with digoxigenin-labeled cRNA probes.
      Double-staining for RALDH1 mRNA and pituitary hormones or S-100 protein, a marker
      of folliculo-stellate cells (FS-cells), has revealed RALDH1 mRNA expression in a
      portion of prolactin-producing cells, marginal layer cells, and FS-cells. Our
      results suggest that RA is generated in the adult anterior pituitary gland, and
      that it may act locally on pituitary cells.

PMID- 17497178
TI  - Differential expression of a subunit isoforms of the vacuolar-type proton pump
      ATPase in mouse endocrine tissues.
AB  - Vacuolar-type proton ATPase (V-ATPase) is a multi-subunit enzyme that couples ATP
      hydrolysis to the translocation of protons across membranes. Mammalian cells
      express four isoforms of the a subunit of V-ATPase. Previously, we have shown
      that V-ATPase with the a3 isoform is highly expressed in pancreatic islets and is
      located in the membranes of insulin-containing granules in the beta cells. The a3
      isoform functions in the regulation of hormone secretion. In this study, we have
      examined the distribution of a subunit isoforms in endocrine tissues, including
      the adrenal, parathyroid, thyroid, and pituitary glands, with isoform-specific
      antibodies. We have found that the a3 isoform is strongly expressed in all these
      endocrine tissues. Our results suggest that functions of the a3 isoform are
      commonly involved in the process of exocytosis in regulated secretion.

PMID- 17497179
TI  - Expression of pigment-epithelium-derived factor during kidney development and
      aging.
AB  - Inhibitors and stimulators of endothelial cell growth are essential for the
      coordination of blood vessel formation during organ growth and development. In
      the adult kidney, one of the major inhibitors of angiogenesis is pigment
      epithelium-derived factor (PEDF). We have analyzed the expression and
      distribution of PEDF during various stages of renal development and aging with
      particular emphasis on the formation of functional glomeruli. We show that PEDF
      gene expression and protein levels in the kidney significantly increase with age.
      We have detected PEDF in the mesenchyme and endothelial cells at all
      developmental stages studied, in all regions of the nephrogenic zone in which the
      formation of new blood vessels is associated with the development of nephrons and
      collecting ducts, and in mature podocytes in the adult kidney. Our results are
      the first to suggest that PEDF is important in early renal postnatal development,
      that it could be relevant to the maturation of glomerular function and the
      filtration barrier formed by these cells, and that it may serve as an anti
      angiogenic modulator during kidney development.

PMID- 17497180
TI  - Climate and species affect fine root production with long-term fertilization in
      acidic tussock tundra near Toolik Lake, Alaska.
AB  - Long-term fertilization of acidic tussock tundra has led to changes in plant
      species composition, increases in aboveground production and biomass and
      substantial losses of soil organic carbon (SOC). Root litter is an important
      input to SOC pools, although little is known about fine root demography in
      tussock tundra. In this study, we examined the response of fine root production
      and live standing fine root biomass to short- and long-term fertilization, as
      changes in fine root demography may contribute to observed declines in SOC. Live
      standing fine root biomass increased with long-term fertilization, while fine
      root production declined, reflecting replacement of the annual fine root system
      of Eriophorum vaginatum, with the long-lived fine roots of Betula nana. Fine root
      production increased in fertilized plots during an unusually warm growing season,
      but remained unchanged in control plots, consistent with observations that B.
      nana shows a positive response to climate warming. Calculations based on a few
      simple assumptions suggest changes in fine root demography with long-term
      fertilization and species replacement could account for between 20 and 39% of the
      observed declines in SOC stocks.

PMID- 17497181
TI  - Selective predation, parasitism, and trophic cascades in a bluegill-Daphnia
      parasite system.
AB  - As disease incidence increases worldwide, there is increased interest in
      determining the factors controlling parasitism in natural populations. Recently,
      several studies have suggested a possible role of predation in reducing
      parasitism, but this idea has received little experimental attention. Here, I
      present the results of an experiment in which I manipulated predation rate in
      large field enclosures to test the effects of predation on parasitism using a
      bluegill predator-Daphnia host-yeast parasite system. Based on previous work
      showing high bluegill sunfish selectivity for infected over uninfected Daphnia, I
      anticipated that predators would reduce infection levels. Contrary to
      expectations, predation did not reduce infection prevalence. Instead, there were
      large epidemics in all treatments, followed by reductions of host density to very
      low levels. As Daphnia density decreased, phytoplankton abundance increased and
      water clarity decreased, suggesting a parasite-driven trophic cascade. Overall,
      these results suggest that selective predation does not always reduce infection
      prevalence, and that parasites have the potential to drastically reduce host
      densities even in the presence of selective predators.

PMID- 17497182
TI  - Linkage study of 14 candidate genes and loci in four large Dutch families with
      vesico-ureteral reflux.
AB  - Vesico-ureteral reflux (VUR) is a major contributing factor to end-stage renal
      disease in paediatric patients. Primary VUR is a familial disorder, but little is
      known about its genetic causes. To investigate the involvement of 12 functional
      candidate genes and two reported loci in VUR, we performed a linkage study in
      four large, Dutch, multi-generational families with multiple affected
      individuals. We were unable to detect linkage to any of the genes and loci and
      could exclude the GDNF, RET, SLIT2, SPRY1, PAX2, AGTR2, UPK1A and UPK3A genes and
      the 1p13 and 20p13 loci from linkage to VUR. Our results provide further evidence
      that there appears to be genetic heterogeneity in VUR.

PMID- 17497183
TI  - [Measuring pressure pain thresholds. Comparison of an electromechanically
      controlled algometer with established methods].
AB  - BACKGROUND: Measurement of the pressure pain threshold and suprathreshold
      pressure pain sensitivity using a newly developed computer controlled algometer
      was compared to established methods in this pilot study. METHODS: The pressure
      pain threshold was measured in 64 chronic pain patients and 37 healthy volunteers
      with a manual electronic algometer (Somedic) and the computer controlled
      Algoforce PA3. Stimulus-response curves with painful stimuli were applied using
      the Algoforce PA3 and a hydraulic algometer. RESULTS: Overall means and variance
      of the pressure pain thresholds for both methods were similar. For low pain
      thresholds the Algoforce PA3 generally resulted in lower values and for high pain
      thresholds in higher values. No differences were seen for suprathreshold pain
      sensitivity. Gender and the presence of chronic pain had no relevant effect on
      the different methods in both comparisons. CONCLUSION: For clinical use, the
      algometers investigated deliver comparable results. For studies requiring high
      precision with low levels of stimulation the use of the Algoforce PA3 could be
      considered.

PMID- 17497184
TI  - [Reduction in pain intensity after treatment for chronic back pain. When is it
      clinically meaningful?].
AB  - AIM: The aim of this study was to evaluate how much change in pain intensity is
      necessary to discriminate between good, bad or no treatment outcome from the
      patient's point of view after therapy for chronic back pain. METHODS: A total of
      153 patients with chronic back pain were admitted to a 3 week multimodal
      treatment program including functional restoration and cognitive behavioral
      support (outpatient). Pain intensity was measured at the beginning of treatment
      and 6 months after discharge using a visual analogue scale (VAS). At this time,
      patients had to evaluate their back pain compared to the beginning of treatment
      as of better, equal or worse (global self-assessment). RESULTS: Six months after
      therapy, 48% of the patients assessed their back pain as better, 28% reported no
      change and 14% stated that their pain was worse. Mean pain reduction among the
      patients who assessed themselves as better was 25 points, while those who stated
      that their pain was worse had an average of 9 points more (VAS). CONCLUSION:
      Patients' global self-assessment is a valid parameter to determine the outcome
      after treatment of chronic back pain. A clinically meaningful pain reduction can
      be assumed if there is at least a 25/100 point reduction (VAS), while a worsening
      of pain is already found to be important when there is a rise of 9/100 points.

PMID- 17497186
TI  - Adolescent scar contracture scoliosis caused by back scalding during the
      infantile period.
AB  - The study design was a retrospective study in adolescent scar contracture
      scoliosis caused by back scalding during the infantile period. The objective of
      the study was to investigate the pathogenesis, clinical manifestation and
      treatment of adolescent scar contracture scoliosis caused by back scalding during
      the infantile period. This condition seldom occurs and is not reported in current
      English literature. One patient was first treated with skin expansion, back scar
      excision and skin flap transfer, followed by anterior correction with TSRH
      instrumentation. Two patients were first treated with back scar excision and
      anterior spinal release. One patient was treated with posterior correction with
      TSRH instrumentation, and thoracoplasty was performed after 50 days in halo
      wheelchair traction. The other patient was treated with posterior correction with
      TSRH instrumentation. No management of scalding was performed on the fourth
      patient. Anterior release and posterior correction were performed at an interval
      of 3 weeks. The deformities of four patients were well corrected. Trunk balance
      was restored and the pelvis leveled. The skin incision wounds healed well. Minor
      loss of correction was recorded during the last follow-up. Severe scar
      contracture caused by back scalding during the infantile period could lead to
      adolescent scoliosis. Its pathogenesis and clinical manifestation are different
      from the typical adolescent idiopathic scoliosis. The treatment of this kind of
      scoliosis should be individualized.

PMID- 17497187
TI  - Harms titanium mesh cage fracture.
AB  - Interbody fusion has become a mainstay of surgical management for lumbar
      fractures, tumors, spondylosis, spondylolisthesis and deformities. Over the
      years, it has undergone a number of metamorphoses, as novel instrumentation and
      approaches have arisen to reduce complications and enhance outcomes. Interbody
      fusion procedures are common and successful, complications are rare and most
      often do not involve the interbody device itself. We present here a patient who
      underwent an anterior L4 corpectomy with Harms cage placement and who later
      developed a fracture of the lumbar titanium mesh cage (TMC). This report details
      the presentation and management of this rare complication, as well as discusses
      the biomechanics underlying this rare instrumentation failure.

PMID- 17497188
TI  - CT-based classification of long spinal allograft fusion.
AB  - Anterior column reconstruction of the thoracolumbar spine by structural allograft
      has an increased potential for biological fusion when compared to synthetic
      reconstructive options. Estimation of cortical union and trabecular in-growth is,
      however, traditionally based on plain radiography, a technique lacking in
      sensitivity. A new assessment method of bony union using high-speed spiral CT
      imaging is proposed which reflects the gradually increasing biological stability
      of the construct. Grade I (complete fusion) implies cortical union of the
      allograft and central trabecular continuity. Grade II (partial fusion) implies
      cortical union of the structural allograft with partial trabecular incorporation.
      Grade III (unipolar pseudarthrosis) denotes superior or inferior cortical non
      union of the central allograft with partial trabecular discontinuity centrally
      and Grade IV (bipolar pseudarthrosis) suggests both superior and inferior
      cortical non-union with a complete lack of central trabecular continuity. Twenty
      five patients underwent anterior spinal reconstruction for a single level burst
      fracture between T4 and L5. At a minimum of two years follow up the subjects
      underwent high-speed spiral CT scanning through the reconstructed region of the
      thoracolumbar spine. The classification showed satisfactory interobserver (kappa
      score = 0.91) and intraobserver (kappa score = 0.95) reliability. The use of high
      speed CT imaging in the assessment of structural allograft union may allow a more
      accurate assessment of union. The classification system presented allows a
      reproducible categorization of allograft incorporation with implications for
      treatment.

PMID- 17497189
TI  - Value of MRI in three patients with major vascular injuries after laparoscopic
      cholecystectomy.
AB  - The aim of this study was to describe three cases of major vascular injuries
      after laparoscopic cholecystectomy depicted on magnetic resonance (MR)
      examination. Three female patients (mean age, 32 years; range, 22-39 years) were
      studied with clinical suspicion of bilio-vascular injuries after laparoscopic
      cholecystectomy. All MR examinations were performed within 24 h after the
      laparoscopic procedure. MR imaging was evaluated for major vascular injuries
      involving the arterial and portal venous system, for bile duct discontinuity,
      presence or absence of biliary dilation, stricture, excision injury, free fluid
      and collections. In the first patient, a type-IV Bismuth injury with associated
      intrahepatic bile ducts dilation was observed. Contrast-enhanced MR revealed lack
      of enhancement in the right hepatic lobe due to occlusion of the right hepatic
      artery and the right portal branch. This patient underwent right hepatectomy with
      hepatico-jejunostomy. In the other two cases, no visualization of the right
      hepatic artery and the right portal branch was observed on MR angiography. In the
      first case, the patient underwent right hepatectomy; in the second case, because
      of stable liver condition, the patient was managed conservatively. MR imaging
      combined with MR angiography and MR cholangiography can be performed emergently
      in patients with suspicion of bilio-vascular injury after laparoscopic
      cholecystectomy allowing the simultaneous evaluation of the biliary tree and the
      hepatic vascular supply that is essential for adequate treatment planning.

PMID- 17497190
TI  - Dynamic modeling for shear stress induced ATP release from vascular endothelial
      cells.
AB  - A dynamic model is proposed for shear stress induced adenosine triphosphate (ATP)
      release from endothelial cells (ECs). The dynamic behavior of the ATP/ADP
      concentration at the endothelial surface by viscous shear flow is investigated
      through simulation studies based on the dynamic ATP release model. The numerical
      results demonstrate that the ATP/ADP concentration against time at endothelium
      fluid interface predicted by the dynamic ATP release model is more consistent
      with the experimental observations than that predicted by previous static ATP
      release model.

PMID- 17497191
TI  - Medicare prescription drug plan costs and affordability--2007.

PMID- 17497192
TI  - Role of Nd:YAG laser for prevention of neuroma formation: an in vivo experimental
      study.
AB  - Nerve transection is commonly followed by the development of neuroma at the
      proximal stump. It can be very painful especially at exposed sites. It may arise
      spontaneously or after mechanical irritation. Neuroma and its high recurrence
      rate might be resisting problems to treat. Various treatment modalities for
      neuroma and its recurrence have been proposed, but none has provided satisfactory
      results. The present study was conducted to evaluate the neodymium:yttrium
      aluminum garnet (Nd:YAG) laser (1,064 nm) nerve transection technique for
      prevention of neuroma formation. There were 48 facial nerves out of 24 Rex
      rabbits divided into two equal groups. The 24 left-sided facial nerves at group A
      were subjected to Nd:YAG laser for nerve transection, while the 24 right-sided
      facial nerves at group B were subjected to scalpel nerve transection. The results
      were grossly and histopathologically evaluated. Grossly, laser-transected nerves
      showed an infrequent incidence of neuroma formation. Histopathologically, laser
      transected nerves showed photothermal degenerative changes of the axons and
      myelin sheaths with intact perineurium and endoneurium. No Schwann cell
      hyperactivity could also be elicited among laser-transected nerves. Nd:YAG laser
      was found to be an effective tool that could be applied, whenever it is possible,
      for division of major nerves to prevent the formation of the subsequent stump
      neuroma. Moreover, this technique should be considered during treatment of well
      established neuroma to prevent the challenging reported high incidence of
      recurrence.

PMID- 17497194
TI  - Nissen fundoplication improves gastric myoelectrical activity characteristics and
      symptoms in gastroesophageal reflux patients: evaluation in transcutaneous
      electrogastrography.
AB  - BACKGROUND: Gastric myoelectrical activity disorders play an essential role in
      the pathophysiology of gastroesophageal reflux disease (GERD), although little is
      known about gastric motility following surgical treatment of the disease. The aim
      of present study was to analyze the impact of Nissen fundoplication on both
      gastric myoelectrical activity, measured using the transcutaneous
      electrogastrography technique (EGG), and change in digestive symptoms. METHODS:
      In 43 patients with GERD, EGG was recorded before and after the Nissen procedure
      and compared with the EGG obtained in eight healthy volunteers. Symptoms of
      epigastric pain, belching, regurgitation, heartburn, postprandial abdominal
      distension, and early satiety were recorded. At a three-week and a one-year
      postoperative follow-up, these tests were repeated. RESULTS: In fasted patients
      before the operation, the slow-wave frequency distribution (normogastria, 53.7%;
      bradygastria, 44.2%; dysrhythmia, 47.1%) was significantly different compared
      with that of controls (89.2%, 7.0%, and 10.4%, respectively). No major changes in
      slow-wave frequency distribution were observed after a meal in examined patients,
      besides a significant rise in tachygastria (12.4%). Three weeks following the
      Nissen fundoplication, the fasting slow-wave frequency distribution did not
      change significantly compared with the preoperative period, being 58.1% for
      normogastria, 43.2% for bradygastria, and 12.0% for tachygastria. The abnormal
      distribution of slow waves (bradygastria + tachygastria) was not significantly
      affected by Nissen fundoplication, being 47.1% before and 44.9% after the
      operation, respectively. At the same time and still one year after operation
      there was a significant improvement in all clinical symptoms measured.
      CONCLUSION: EGG showed that Nissen fundoplication influenced and might improve
      the slow-wave generation in gastric pacemaker. Dyspeptic symptoms were also
      improved up to one year postoperatively.

PMID- 17497195
TI  - Phylogenetic diversity and distribution of dissimilatory sulfite reductase genes
      from deep-sea sediment cores.
AB  - The diversity and distribution of sulfate-reducing prokaryotes (SRP) was
      investigated in the Nankai Trough sediments of off-central Japan by exploring the
      diversity of a functional gene, dissimilatory sulfite reductase (dsrAB). Bulk
      DNAs were extracted from five piston-cored samples (up to 4.5 m long) with 41
      vertical sections, and full-length dsrABgene sequences (ca. 1.9 kb) were PCR
      amplified and cloned. A total of 382 dsrAB clones yielded eight phylogenetic
      groups with an indigenous group forming a unique dsrAB lineage. The
      deltaproteobacterial dsrAB genes were found in almost all sediment samples,
      especially in the surface layer. One unique dsrAB clone group was also widespread
      in the dsrAB profiles of the studied sediments, and the percentage of its clones
      was generally shown gradual increase with sediment depth.

PMID- 17497196
TI  - Marine biofilms as mediators of colonization by marine macroorganisms:
      implications for antifouling and aquaculture.
AB  - In the marine environment, biofilms on submerged surfaces can promote or
      discourage the settlement of invertebrate larvae and macroalgal spores. The
      settlement-mediating effects of biofilms are believed to involve a variety of
      biofilm attributes including surface chemistry, micro-topography, and a wide
      range of microbial products from small-molecule metabolites to high-molecular
      weight extracellular polymers. The settled organisms in turn can modify microbial
      species composition of biofilms and thus change the biofilm properties and
      dynamics. A better understanding of biofilm dynamics and chemical signals
      released and/or stored by biofilms will facilitate the development of antifouling
      and mariculture technologies. This review provides a brief account of 1) existing
      knowledge of marine biofilms that are relevant to settlement mediation, 2)
      biotechnological application of biofilms with respect to developing non-toxic
      antifouling technologies and improving the operation of aquaculture facilities,
      and 3) challenges and future directions for advancing our understanding of
      settlement-mediating functions of biofilms and for applying this knowledge to
      real-life situations.

PMID- 17497197
TI  - Extended query refinement for medical image retrieval.
AB  - The impact of image pattern recognition on accessing large databases of medical
      images has recently been explored, and content-based image retrieval (CBIR) in
      medical applications (IRMA) is researched. At the present, however, the impact of
      image retrieval on diagnosis is limited, and practical applications are scarce.
      One reason is the lack of suitable mechanisms for query refinement, in
      particular, the ability to (1) restore previous session states, (2) combine
      individual queries by Boolean operators, and (3) provide continuous-valued query
      refinement. This paper presents a powerful user interface for CBIR that provides
      all three mechanisms for extended query refinement. The various mechanisms of man
      machine interaction during a retrieval session are grouped into four classes: (1)
      output modules, (2) parameter modules, (3) transaction modules, and (4) process
      modules, all of which are controlled by a detailed query logging. The query
      logging is linked to a relational database. Nested loops for interaction provide
      a maximum of flexibility within a minimum of complexity, as the entire data flow
      is still controlled within a single Web page. Our approach is implemented to
      support various modalities, orientations, and body regions using global features
      that model gray scale, texture, structure, and global shape characteristics. The
      resulting extended query refinement has a significant impact for medical CBIR
      applications.

PMID- 17497198
TI  - Anal sphincter advancement flap for low transsphincteric anal fistula.
AB  - Laying open a transsphincteric anal fistula can be associated with risk of
      incontinence, especially in females. Therefore, an alternative option should be
      available to preserve the sphincter mechanism and cure the anal fistula. This
      article illustrates a new technique of using the distal part of the anal
      sphincter as an advancement flap to cover the internal opening and thereby effect
      a cure. In selected cases, anal sphincter advancement flap for low
      transsphincteric anal fistula is safe, effective, and has a low risk of
      incontinence.

PMID- 17497201
TI  - A male sex pheromone in a scorpionfly.
AB  - It has been postulated that males of a number of scorpionfly species produce sex
      pheromones. This is based on the observation that females often respond only to
      conspecific males when they evert their genital pouch, the proposed site of
      pheromone release. In this study, we prove that in Panorpa germanica (Mecoptera,
      Panorpidae), the eversion of a male's genital pouch is associated with the
      release of a volatile sex pheromone. In dual choice situations, females showed a
      high preference for 'calling' (males with everted genital pouch) over noncalling
      individuals. Volatiles emitted by males and females were collected and identified
      by coupled gas chromatography-mass spectrometry. Two aldehydes [(2E,6Z)-nona-2,6
      dienal and (E)-non-2-enal] were characteristic of calling males but not of
      noncalling or immature males or females. Bioassays with synthetic compounds
      confirmed that the identified substances are attractive to females. To the best
      of our knowledge, this is the first identification of a sex pheromone in
      scorpionflies.

PMID- 17497202
TI  - Estimation of the comparative therapeutic superiority of QD and BID dosing
      regimens, based on integrated analysis of dosing history data and
      pharmacokinetics.
AB  - Once-daily dosing almost invariably shows a slightly higher percentage of
      prescribed doses taken than does twice-daily dosing. Many pharmaceutical
      scientists, regulators, and prescribers have considered this finding to signify
      the therapeutic superiority of once-daily dosing. The therapeutically more
      relevant question, however, is not the percentage of prescribed doses taken but
      the comparative impact of missed doses on the pharmacologic effects of a drug
      under the two dosing regimens. A key point in this regard is that the
      pharmacokinetic equivalent of a single missed once-daily dose is 2-3 sequentially
      omitted twice-daily doses. Thus, an important parameter in comparing the two
      regimens is the probability of two or three twice-daily doses being sequentially
      omitted, versus the probability of missing a single once-daily dose. Our data
      indicate that the probability of sequential omission of 2-3 twice daily doses is
      half the probability of omission of a single once-daily dose. For that reason, a
      twice-daily regimen could prove to be superior to a once-daily regimen in
      maintaining drug concentrations within a therapeutically desirable range. A more
      important consideration, however, is to maintain not just the concentration of
      drug in plasma, but the drug's therapeutic action. The duration of therapeutic
      drug action following a last-taken dose is not only drug-specific, but also, for
      some drug, dependent on the pharmacodynamic properties. Judging the comparative
      superiority of one dosing regimen over another requires knowledge of the drug's
      duration action after a last-taken dose, plus knowledge of the comparative
      probabilities of the various patterns of dose omission. When applied to HIV
      protease inhibitors, a twice-daily regimen appears to be better than an once
      daily regimen in maintaining therapeutically effective drug actions.

PMID- 17497203
TI  - Weighted target interval stochastic control methods with global optimization and
      their applications in individualizing therapy.
AB  - Several improvements on the target interval stochastic control (TISC) method are
      addressed for individualizing therapy. In particular, a global optimization
      control strategy is implemented to obtain the optimal dosage regimen, and
      weighting functions are introduced to balance the drug efficacy and the risk of
      toxicity. Since general guidance is often lacking in the determination of a
      weighting function, we introduce a systematic approach, i.e., the standard
      reference gamble method of medical decision theory, for the determination of the
      weighting function. The population model for the individualization of
      theophylline therapy reported by D'Argenio and Katz is applied in this research.
      The present method of the integration of weighting functions and global optimal
      strategy offer an effective and safe means to balance the drug efficacy and risk
      of toxicity. In addition, it also achieves better accuracy than the existing TISC
      method which uses a local optimal strategy.

PMID- 17497205
TI  - Abstracts of the 3rd Annual Congress of the European Cardiac Arrhythmia Society,
      June 3-5, 2007, Marseille, France.

PMID- 17497204
TI  - Anti-inflammation role for mesenchymal stem cells transplantation in myocardial
      infarction.
AB  - The aim of the present study was to investigate the role of anti-inflammation for
      MSCs transplantation in rat models of myocardial infarction. Rats with AMI
      induced by occlusion of the left coronary artery were randomized to MSCs
      transplantation group, MI group and sham operated group. The effects of MSCs
      transplantation on cardiac inflammation and left ventricular remodeling in non
      infarcted zone were observed after 4 weeks of MI. We found that MSC
      transplantation (1) decreased protein production and gene expression of
      inflammation cytokines TNF-alpha, IL-1beta and IL-6, (2) inhibited deposition of
      type I and III collagen, as well as gene and protein expression of MMP-1 and TIMP
      1, (3) attenuated LV cavitary dilation and transmural infarct thinning, thus
      prevent myocardial remodeling after myocardial infarction, and (4) increased EF,
      FS, LVESP and dp/dtmax (P < 0.01), decreased LVDd, LVEDV, LVEDP (P < 0.05). Anti
      inflammation role for MSCs transplantation might partly account for the cardiac
      protective effect in ischemic heart disease.

PMID- 17497213
TI  - Complete genomic sequence of Dracaena mottle virus, a distinct badnavirus.
AB  - The genome of Dracaena mottle virus (DrMV) was cloned from infected Dracaena
      sanderiana plants, and its complete nucleotide sequence was determined and
      analyzed. The circular DNA genome consists of 7531 base pairs (bp) and possesses
      seven putative open reading frames (ORFs) on the plus-strand that potentially
      encode proteins of 17.6, 14.9, 215.0, 11.9, 11.3, 16.1, and 11.0 kDa,
      respectively. ORF 3, the largest ORF, encodes a putative polyprotein that
      contains sequences for viral aspartyl proteinase, reverse transcriptase (RT) and
      ribonuclease H (RNase H), characteristic of pararetroviruses. Phylogenetic
      analysis based on the amino acid sequence of ORF 3 showed that DrMV is related to
      other badnaviruses. However, the nucleotide sequence coding for the RT and RNase
      H domain of DrMV shares less than 68% homology with that of any known
      badnaviruses. The seventh ORF of DrMV is not found in other badnaviruses
      described before. Our results strongly support that DrMV is a distinct species of
      the genus Badnavirus, family Caulimoviridae. Evidence that the DrMV sequence is
      integrated in the D. sanderiana genome is presented and discussed.

PMID- 17497212
TI  - Immunization of DNA vaccine encoding C3d-VP1 fusion enhanced protective immune
      response against foot-and-mouth disease virus.
AB  - Because foot-and-mouth disease virus (FMDV) remains a great problem to many
      livestock of agricultural importance, safe, effective vaccines are in great need.
      DNA vaccine would be a promising candidate but the design remains to be
      optimized. VP1 gene of FMDV strain O/ES/2001 was linked to three copies of either
      porcine or murine C3d or four copies of a 28-aa fragment of murine C3d containing
      the CR2 receptor binding domain (M28). The resultant plasmids encoding C3d/M28
      VP1 fusion or only VP1 as control were immunized guinea pigs. Both cellular and
      humoral immune responses were evaluated and protection was observed after virus
      challenge. As a result, although the plasmid encoding only VP1 could elicit virus
      binding antibody detected by ELISA, splenocyte proliferation, IL-4 and IFN-gamma
      production, the levels were significantly less than C3d/M28-VP1 fusion.
      Furthermore, VP1 failed to induce neutralization antibody and protect animals
      against virus challenge, while murine C3d-VP1 fusion efficiently induced
      neutralization antibody response and provided 87.50% of the animals with complete
      protection and 12.50% with partial protection. Among murine C3d, M28, and porcine
      C3d, the adjuvant effect of murine C3d is strongest, followed by porcine C3d, and
      last murine M28. In conclusion, the fact that C3d genes, when coupled to VP1
      gene, are able to greatly enhance the protective immune response of VP1 DNA in
      guinea pigs suggests that C3d-VP1 DNA chimera has a significant potential for use
      as a novel DNA vaccine against FMDV.

PMID- 17497214
TI  - Analysis of the molecular and biological variability of zucchini yellow mosaic
      virus isolates from Slovakia and Czech Republic.
AB  - The diversity of ZYMV isolates was analysed by the biological and molecular
      characterisation of 11 isolates sampled from cucumber, squash and zucchini
      between 2001 and 2006 in various localities of Slovakia and Czech Republic.
      Analysis of the molecular variability targeting three separate genomic regions of
      the ZYMV genome [P1, P3 and (Cter)NIb-(Nter)CP] revealed a remarkable low level
      of nucleotide variability between isolates, despite their temporal and spatial
      distinction. Phylogenetic analysis based on the 5'-terminal part of the CP gene
      highlighted the close relatedness of Slovak, Czech and other central European
      isolates. Low level of genetic diversity within central European ZYMV isolates is
      in contrast to the diversity observed for isolates from other geographical
      regions, in particular Asia. No evidence of recombination in the ZYMV genome was
      detected. Sequence comparison between aggressive and moderate ZYMV isolates
      revealed one amino acid difference in the N-terminal part of the P3 protein,
      potentially involved in the tolerance breaking.

PMID- 17497216
TI  - Attribution of blame, self-forgiving attitude and psychological adjustment in
      women with breast cancer.
AB  - The purpose of this study was to examine relationships among self-blame for
      developing breast cancer, a self-forgiving attitude, mood, and quality of life
      among women with breast cancer. In this cross-sectional study, 123 women with
      Stages 0-III breast cancer completed questionnaires measuring demographic and
      medical characteristics, self-blame, self-forgiveness, mood, and quality of life.
      Women who blamed themselves reported more mood disturbance (p <or= .001) and
      poorer quality of life (p < .001) than those who did not blame themselves.
      Mediational analyses revealed that self-blame for cancer partially mediated the
      relationships between a self-forgiving attitude and both mood disturbance and
      quality of life (Z = -2.72, p = .006 and Z = -2.89, p = .004, respectively).
      Patients may benefit from a discussion with their oncologists and other
      healthcare providers about self-forgiveness and the potential benefits of
      reducing self-blame to facilitate adjustment to breast cancer.

PMID- 17497217
TI  - Ongoing risk behavior among persons with HIV in medical care.
AB  - We surveyed randomly selected patients in the largest HIV clinic in Seattle, WA
      in 2005 and 2006. A total of 397 patients completed usable surveys. Twenty-seven
      percent of men who have sex with men (MSM) and 22% of women or heterosexual men
      reported having non-concordant unprotected anal or vaginal intercourse in the
      preceding year. Compared to 2005, more MSM in 2006 reported meeting a sex partner
      via the Internet (15% vs. 33%), and fewer met partners in bathhouses (23% vs.
      13%). Twenty-four percent of MSM reported deciding not to have sex with a
      potential partner because he was HIV negative, and 31% of MSM reported that
      another man had decided not to have sex with them because they were HIV positive.
      Among all participants, 22% had told a sex partner they were HIV negative since
      their HIV diagnosis. These findings demonstrate the persistence of high-risk
      behavior among persons with HIV, a rapid increase in the use of the Internet
      among MSM to find sex partners, and provide direct evidence for serosorting among
      MSM.

PMID- 17497218
TI  - Social, behavioural, and intervention research among people of Sub-Saharan
      African origin living with HIV in the UK and Europe: literature review and
      recommendations for intervention.
AB  - Africans are the second largest group affected by HIV in Western Europe after men
      who have sex with men (MSM). This review describes and summarises the literature
      on social, behavioural, and intervention research among African communities
      affected by HIV in the UK and other European countries in order to make
      recommendations for future interventions. We conducted a keyword search using
      Embase, Medline and PsychInfo, existing reviews, 'grey literature', as well as
      expert working group reports. A total of 138 studies met our inclusion criteria;
      31 were published in peer-reviewed journals, 107 in the grey literature. All peer
      reviewed studies were observational or "descriptive," and none of them described
      HIV interventions with African communities. However, details of 36 interventions
      were obtained from the grey literature. The review explores six prominent themes
      in the descriptive literature: (1) HIV testing; (2) sexual lifestyles and
      attitudes; (3) gender; (4) use of HIV services; (5) stigma and disclosure (6)
      immigration status, unemployment and poverty. Although some UK and European
      interventions are addressing the needs of African communities affected by HIV,
      more resources need to be mobilised to ensure current and future interventions
      are targeted, sustainable, and rigorously evaluated.

PMID- 17497220
TI  - Evaluating mitochondrial membrane potential in cells.
AB  - Permeant cationic fluorescent probes are widely employed to monitor mitochondrial
      transmembrane potential and its changes. The application of such potential
      dependent probes in conjunction with both fluorescence microscopy and
      fluorescence spectroscopy allows the monitoring of mitochondrial membrane
      potential in individual living cells as well as in large population of cells.
      These approaches to the analysis of membrane potential is of extremely high value
      to obtain insights into both the basic energy metabolism and its dysfunction in
      pathologic cells. However, the use of fluorescent molecules to probe biological
      phenomena must follow the awareness of some principles of fluorescence emission,
      quenching, and quantum yield since it is a very sensitive tool, but because of
      this extremely high sensitivity it is also strongly affected by the environment.
      In addition, the instruments used to monitor fluorescence and its changes in
      biological systems have also to be employed with cautions due to technical limits
      that may affect the signals. We have therefore undertaken to review the most
      currently used analytical methods, providing a summary of practical tips that
      should precede data acquisition and subsequent analysis. Furthermore, we discuss
      the application and feasibility of various techniques and discuss their
      respective strength and weakness.

PMID- 17497221
TI  - Genetic diversity and population differentiation of chestnut blight fungus,
      Cryphonectria parasitica, in China as revealed by RAPD.
AB  - Seventeen Cryphonectria parasitica populations sampled from six regions in China
      were investigated using RAPD. Across all 169 isolates from the 17 populations
      evaluated, 52 of the 71 markers (73%) were polymorphic, total genetic diversity
      (h) was 0.1463, and Shannon's index was 0.2312. Diversity within populations
      accounted for 74% of total genetic diversity, and genetic differentiation among
      populations was 0.26 (G (ST) = 0.26). Gene flow was 1.4 among the populations;
      higher gene flow was found among populations within regions and among regions [N
      (m) (G (SR)) = 2.8 and N (m) (G (RT)) = 3.5]. The unweighted pair group mean
      analysis (UPGMA) dendrogram revealed two distinct clusters: the northern China
      group and the southern China group. The spatial autocorrelation analysis revealed
      that the variation at most loci was randomly distributed and lacked spatial
      structure, but several loci and closer distances were spatially structured. Human
      activity and habitat could also be important factors affecting genetic structure
      among C. parasitica populations in China. Genetic diversity was highest in
      Southwest China, descending in an orderly fashion to Northeast China. This
      pattern indicated that Southwest China might be the center of origin of C.
      parasitica in China. The present study provides useful information for
      understanding the origin and spread of chestnut blight fungus in China and
      valuable data for formulating relevant strategies for controlling the disease in
      China.

PMID- 17497219
TI  - Housing stability over two years and HIV risk among newly homeless youth.
AB  - The stability of living situation was examined as a predictor of young people's
      HIV-related sexual and drug use acts two years after leaving home for the first
      time. Newly homeless youth aged 12-20 years were recruited in Los Angeles County,
      California, U.S.A. (n = 261) and Melbourne, Australia (n = 165) and followed
      longitudinally at 3, 6, 12, 18, and 24 months. Their family history of moves and
      the type and frequency of moves over the two years following becoming newly
      homeless were examined. Regression analyses indicated that recent sexual risk two
      years after becoming newly homeless was not related to the instability of youths'
      living situations; condom use was higher among youth with more placements in
      institutional settings and among males. Drug use was significantly related to
      having moved more often over two years and Melbourne youth used drugs
      significantly more than youth in Los Angeles.

PMID- 17497223
TI  - Human papillomavirus vaccine: knowledge and attitudes in two Appalachian Kentucky
      counties.
AB  - OBJECTIVE: A vaccine against common high-risk types of human papillomavirus (HPV)
      associated with cervical cancer risk was recently approved. We assessed women's
      acceptance of HPV vaccination for themselves and for adolescent girls, in an
      Appalachian population with cervical cancer incidence and mortality rates among
      the highest in the United States. METHODS: We conducted a population-based,
      random-digit telephone survey of over 600 adult women residing in two Appalachian
      Kentucky counties. The analysis focused on questions of HPV vaccine acceptance,
      and their relationship to several factors. RESULTS: The majority of women
      indicated an interest in HPV vaccination for themselves (85.2%), but they were
      less accepting of a vaccine being administrated to girls of ages 10-15 (67.6%).
      Women who were younger, lower-income and smokers were more likely to support
      vaccination. CONCLUSIONS: Although a relatively high percentage of women found
      the HPV vaccination acceptable for their own use, there was less enthusiasm for
      supporting vaccination to girls. This finding is of concern since the vaccine is
      being recommended for adolescent girls and young women, prior to sexual
      initiation. Educational campaigns will be needed for a successful vaccine
      implementation.

PMID- 17497222
TI  - The diagnostic yield of various tests for Helicobacter pylori infection in
      patients on acid-reducing drugs.
AB  - The diagnostic yield of various tests for Helicobacter pylori infection in
      patients on acid-reducing drugs, such as proton pump inhibitors (PPI) and
      histamine-2 receptor blocker (H2RB), was compared. Seventy-four consecutive
      patients on acid-reducing drugs were enrolled: 34 (46%) were on PPIs, 20 (27%)
      were on H2RBs and 20 (27%) were not on medications. For those patients on PPIs,
      RUT and histology results from antrum were negative in 28 (82%) and 17 (50%)
      patients, respectively (OR: 4.7; 95% CI: 1.4-16.6; P = 0.004), while those from
      the corpus were negative in was 28 (82%) and 18 (53%) patients, respectively (OR:
      4.4, 95% CI: 1.3-15.5; P = 0.006). For patients on H2RBs, RUT and histology
      results from the antrum were negative in 12 (60%) and six (30%) patients,
      respectively (OR: 3.5; 95% CI: 0.8-16.1; P = 0.05), while those from the corpus
      were negative in 12 (60%) and nine (45%) patients, respectively (OR: 1.8; 95% CI:
      0.4-7.8; P = 0.342). For those patients on PPIs, the diagnostic yield of both RUT
      and histology was reduced from both the antrum and corpus. In these patients, PCR
      for H. pylori is more sensitive than RUT and histology.

PMID- 17497224
TI  - A survey of Estonian consumer expectations from the pharmacy service and a
      comparison with the opinions of pharmacists.
AB  - OBJECTIVE: To assess the preferences of pharmacy customers when choosing a
      pharmacy and their expectations of the service, and comparing these with the
      opinions of pharmacists. MAIN OUTCOME MEASURE: Opinion and satisfaction of
      community pharmacy clients in Estonia. METHODS: A written survey was carried out
      among pharmacy customers (n=1979) in cities (in 3 community pharmacies), towns
      (in 2 community pharmacies), and in small towns (in 2 community pharmacies). The
      survey was also carried out among community pharmacists (n=135) in different
      regions of Estonia. RESULTS: When choosing a pharmacy, its location was
      considered most important, costs and wide choice are less important. The most
      important expectations of customers' included help choosing the right medicine,
      as well as professional consultation. Preferences and expectations of pharmacy
      customers depended on their age, gender and income. Parking space, quickness and
      pleasantness were considered important by men. Costs and wide choice were
      considered to be more important by women. Pharmacists wish to give patients more
      information, but they overestimate the importance of quick service. Customers
      favoured privacy, discretion and confidentiality more. These characteristics were
      especially important to younger well-paid people living in big cities.
      CONCLUSION: In contrast to the opinions offered by pharmacists', a rapid customer
      service is so not as important as the quality of service in pharmacy according to
      customers. They also emphasised that pharmacies should highlight the choice of
      products, quality of service, a professional consultation, as well as ensure
      privacy.

PMID- 17497225
TI  - Carbon acquisition by diatoms.
AB  - Diatoms are responsible for up to 40% of primary productivity in the ocean, and
      complete genome sequences are available for two species. However, there are very
      significant gaps in our understanding of how diatoms take up and assimilate
      inorganic C. Diatom plastids originate from secondary endosymbiosis with a red
      alga and their Form ID Rubisco (ribulose-1,5-bisphosphate carboxylase-oxygenase)
      from horizontal gene transfer, which means that embryophyte paradigms can only
      give general guidance as to their C acquisition mechanisms. Although diatom
      Rubiscos have relatively high CO(2) affinity and CO(2)/O(2) selectivity, the low
      diffusion coefficient for CO(2) in water has the potential to restrict the rate
      of photosynthesis. Diatoms growing in their natural aquatic habitats operate
      inorganic C concentrating mechanisms (CCMs), which provide a steady-state CO(2)
      concentration around Rubisco higher than that in the medium. How these CCMs work
      is still a matter of debate. However, it is known that both CO(2) and HCO (3) (-)
      are taken up, and an obvious but as yet unproven possibility is that active
      transport of these species across the plasmalemma and/or the four-membrane
      plastid envelope is the basis of the CCM. In one marine diatom there is evidence
      of C(4)-like biochemistry which could act as, or be part of, a CCM. Alternative
      mechanisms which have not been eliminated include the production of CO(2) from
      HCO (3) (-) at low pH maintained by a H(+) pump, in a compartment close to that
      containing Rubisco.

PMID- 17497226
TI  - Frequency distribution of the G/A alleles of the beta-fibrinogen gene in the
      Lebanese population.
AB  - Fibrinogen is a plasma protein that has been reported to be associated with an
      increased risk of atherothrombotic diseases and venous thrombosis. The most
      common polymorphism that has been studied so far in different populations is the
      G-455-->A polymorphism in the promoter region of the beta-fibrinogen gene. We
      studied 160 healthy unrelated Lebanese individuals for the prevalence of -455G/G,
      -455G/A and -455A/A genotypes of the beta-fibrinogen gene and the frequency of G
      and A alleles using a reverse hybridization PCR assay. The prevalence of the G/G,
      G/A, and A/A genotypes were found to be 60.6, 31.9 and 7.5%, respectively. The
      frequency of the G and A alleles were found to be 0.77 and 0.23, respectively. As
      compared to other ethnic groups, the Lebanese individuals were found to have a
      relatively high prevalence of the A allele which may predispose them to develop
      cardiovascular diseases as well as thrombotic events. This study provides
      additional unique genetic information pertaining to the Lebanese population.

PMID- 17497227
TI  - Psychopharmacology and the self: an introduction to the theme.

PMID- 17497228
TI  - Abundance and bioactivity of cultured sponge-associated bacteria from the
      Mediterranean sea.
AB  - In this study, the search for new antibiotics was combined with quantitative
      ecological studies. The cultured fraction of the associated bacterial communities
      from ten different Mediterranean sponge species was investigated. To obtain
      quantitative and qualitative data of sponge-associated bacterial communities and
      to expand the cultured diversity, different media were used. The largest
      morphological diversity and highest yield of isolates was obtained by using
      oligotrophic media, which consisted of natural habitat seawater amended with (1%
      additional carbon sources. The dominant bacterial morphotypes were determined and
      bacterial isolates were tested for antimicrobial activity and identified using
      16S rDNA sequencing. The sponge-associated most abundant morphotypes were all
      affiliated to the Alphaproteobacteria and showed antimicrobial activity against
      at least one of the tested strains. In contrast, the ambient seawater was
      dominated by Gammaproteobacteria. One single alphaproteobacterium, which was
      related to Pseudovibrio denitrificans, was shown to dominate the cultured
      community of at least six of the sponges. This designated MBIC3368-like
      alphaproteobacterium has been isolated from sponges before and seems to be
      restricted to associations with members of the phylum Porifera. It displays a
      weak and unstable antimicrobial activity, which gets easily lost during
      cultivation. However, this bioactive bacterium was present in the sponges by up
      to 10(6) cells per gram wet-weight sponge tissue and dominated the cultured
      fraction with up to 74%. The association of this alphaproteobacterium with
      sponges is probably evolutionary young and facultative and possibly involves
      biologically active secondary metabolites. Besides a demonstrated vertical
      transfer, additional horizontal transfer between the sponges is assumed. Members
      of the genus Bacillus displaying antimicrobial activity were found regularly,
      too. However, actinomycetes, which are known for their production of bioactive
      substances, were present in very low abundance.

PMID- 17497230
TI  - A simple and rapid method for cryopreservation of Trichomonas vaginalis.
AB  - A pellet freezing method, one type of rapid freezing protocol, was established
      for Trichomonas vaginalis. As cryoprotectants, 5-20% dimethylsulfoxide (DMSO),
      ethylene glycol, propylene glycol, and glycerol were used. Of these, DMSO showed
      a high protective effect, with a maximum effect at a concentration of 20%. No
      effect of equilibration time was recognized with any of the cryoprotectants.
      Therefore, the optimal condition was deemed 20% DMSO without equilibration. The
      pellet freezing method was also compared with the conventional slow cooling
      protocol. The survival rate was 73 +/- 8% with the slow cooling protocol and 48
      +/- 4% with the pellet freezing method. The delay in growth with the pellet
      freezing method was no more than 5.4 h compared with the slow cooling protocol,
      suggesting its validity as a technique for cryopreservation of T. vaginalis.

PMID- 17497229
TI  - Prenatal exposure to valproic acid disturbs the enkephalinergic system
      functioning, basal hedonic tone, and emotional responses in an animal model of
      autism.
AB  - RATIONALE: It has been suggested that behavioral aberrations observed in autism
      could be the result of dysfunction of the neuroregulatory role performed by the
      endogenous opioid peptides. Many of those aberrations have been recently modeled
      in rats exposed to valproic acid (VPA) on the 12th day of gestation (VPA rats).
      OBJECTIVES: The aim of the present study was to elucidate functioning of the
      enkephalinergic system, one of the endogenous opioid peptide systems strongly
      involved in emotional responses, in VPA rats using both biochemical and
      behavioral methods. MATERIALS AND METHODS: In situ hybridization was used to
      measure proenkephalin mRNA expression in adult VPA rats' central nucleus of the
      amygdala, the dorsal striatum, and the nucleus accumbens. Additional groups of
      animals were examined in a conditioned place aversion to naloxone, the elevated
      plus maze, and object recognition tests to assess their basal hedonic tone,
      anxiety, learning and memory, respectively. RESULTS: Prenatal exposure to VPA
      decreased proenkephalin mRNA expression in the dorsal striatum and the nucleus
      accumbens but not in the central nucleus of the amygdala. It also increased
      anxiety and attenuated conditioned place aversion to naloxone but had no impact
      on learning and memory. CONCLUSIONS: The present results suggest that prenatal
      exposure to VPA may lead to the decreased activity of the striatal
      enkephalinergic system and in consequence to increased anxiety and disregulated
      basal hedonic tone observed in VPA rats. Presented results are discussed in light
      of interactions between enkephalinergic, GABAergic, and dopaminergic systems in
      the striatum and mesolimbic areas of the brain.

PMID- 17497231
TI  - Higher level gait disorders.
AB  - This short review is derived from the contributions of the authors at a meeting
      on gait disorders and higher mental function held in Madrid in February 2006 and
      is submitted at the request of the meeting convenor, Dr N Giladi.

PMID- 17497232
TI  - Detection of the virulent Marek's disease virus genome from feather tips of wild
      geese in Japan and the Far East region of Russia.
AB  - Marek's disease (MD) virus (MDV) is known to cause malignant lymphomas in
      chickens. In 2001, we first reported an MD case in a white-fronted goose (Anser
      albifrons) in Japan. Therefore, the prevalence of MDV in the wild geese was
      surveyed by nested PCR using feather-tip samples in Japan and the Far East region
      of Russia, breeding habitats of geese migrating to Japan. MDV was detected in
      about 30% of analyzed white-fronted geese. Furthermore, by nucleotide sequence
      analysis, we confirmed that this MDV shows high homology to very virulent MDV,
      suggesting that highly virulent MDV is widespread in white-fronted geese
      migrating between Japan and Far East region of Russia.

PMID- 17497233
TI  - Homologous recombination plays minor role in excision of unit-length viral
      genomes from head-to-tail direct tandem repeats of porcine circovirus during DNA
      replication in Escherichia coli.
AB  - In this report, we confirmed previous work that a theta-replicating bacterial
      plasmid containing 1.75 copies of genomic porcine circovirus (PCV) DNA in head-to
      tail tandem (HTT) [a partial copy of PCV type 1 (PCV1), a complete copy of PCV
      type 2 (PCV2) and two origins of DNA replication (Ori)] yielded three different
      double-stranded DNA species when transformed into Escherichia coli: the input
      construct (U), the unit-length PCV1/PCV2 genome with a composite Ori lacking the
      plasmid vector (Q(RC)) and the remaining left-over 0.75 copy PCV1/PCV2 genome
      with a different composite Ori inserted in the plasmid vector (L(RC)).
      Replication of U was presumably via the theta-like replication mechanism
      utilizing the colicin E1 Ori, while derivation of L(RC) and Q(RC) was via the
      rolling-circle replication (RCR) copy-release mechanism and required the presence
      of two PCV Oris and the virus-encoded Rep protein. Essentially, excision of a
      unit-length PCV1/PCV2 genome (Q(RC)) via RCR from U yielded L(RC). Furthermore,
      we examined whether homologous recombination may also result in excision of a
      different type of unit-length PCV genome (Q(H)) from identical HTT constructs to
      generate L(H). Whereas the generation of L(RC) is Rep-protein-dependent, the
      generation of L(H) is Rep-protein-independent. Accordingly, the L(RC) and Q(RC)
      molecules derived from RCR possess different characteristics from the L(H) and
      Q(H) molecules generated via homologous recombination. In one of the studies in
      which both L(RC) and L(H) were generated simultaneously from the same HTT
      construct, out of 69 samples analyzed, 66 were derived via RCR and 3 were derived
      via homologous recombination. Thus, in comparison with RCR, homologous
      recombination plays a minor role in the excision of unit-length PCV genomes from
      HTT constructs in Escherichia coli.

PMID- 17497234
TI  - The complete genome sequence for an American isolate of enterovirus 77.

PMID- 17497235
TI  - Canna yellow streak virus: a new potyvirus associated with severe streaking
      symptoms in canna.
AB  - A new potyvirus has been found in canna. A 1700-nucleotide region at the 3' end
      of the genomic RNA has been sequenced from two isolates. The sequence reveals the
      virus to be a distinct member of the genus Potyvirus but most closely related to
      Johnsongrass mosaic virus. A specific primer pair was designed that enabled canna
      material to be screened specifically for this virus. The virus was consistently
      found in cannas showing severe virus symptoms. This virus has been found in
      different canna varieties from the UK, Belgium, Netherlands, France and Israel.
      The name Canna yellow streak virus (CaYSV) has been proposed for this new virus.

PMID- 17497236
TI  - Genetic diversity of Brazilian strains of porcine circovirus type 2 (PCV-2)
      revealed by analysis of the cap gene (ORF-2).
AB  - Porcine circovirus 2 (PCV-2) is associated with a broad range of syndromes. In
      this study, 19 of 870 samples from pigs from different Brazilian states were
      found to be positive for PCV-2 by polymerase chain reaction (PCR). A fragment of
      700 nt of the cap gene (ORF-2) from the 19 PCV-2-positive samples were sequenced
      using three pairs of primers (Fa/Ra, Fb/Rb and Fc/Rc). Maximum parsimony
      genealogy with a heuristic algorithm using the 19 field strain studied here, 21
      sequences from GenBank and PCV-1 as an out-group showed the existence of two
      major clusters (A and B) and the Brazilian strains segregating in both of them.
      PCV-2 was found in pigs with various clinical signs. No association between
      clusters of PCV-2 and different states or clinical signs were observed,
      demonstrating that the exact role of PCV-2 in porcine circovirus diseases (PCVD)
      in Brazil still needs to be clarified. These results contribute to the molecular
      characterization of PCV-2, which serve as a basis for the epimiology of PCV-2
      infection.

PMID- 17497237
TI  - Susceptibility of cyprinid cultured cells to cyprinid herpesvirus 3.
AB  - Cyprinid herpesvirus 3 is a highly contagious and lethal virus that affects
      ornamental koi and common carp worldwide. However, it is not yet known whether
      other cyprinids are infected and/or harbor the virus. Here, we report that
      cultured cells derived from common carp, koi, silver carp and goldfish allow CyHV
      3 propagation, while cyprinid cells derived from fathead minnow and non-cyprinid
      cells derived from the channel catfish ovary are resistant to CyHV-3 infection.
      Interestingly, the epithelioma papulosum Cyprini cells derived from Cyprinus
      carpio are restrictive to the virus. These results indicate that CyHV-3 is not
      restricted to common carp and koi, but other cyprinids are also vulnerable to the
      virus.

PMID- 17497238
TI  - Antiviral activity of arbidol against influenza A virus, respiratory syncytial
      virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo.
AB  - Arbidol, ethyl-6-bromo-4-[(dimethylamino)-methyl]-5-hydroxy-1-methyl-2
      [(phenylthio)methyl]-in dole-3-carboxylate hydrochloride monohydrate, is an
      antiviral chemical agent. In this report, we studied the antiviral activity of
      arbidol against a panel of human respiratory viruses, namely influenza A virus
      (FLU-A, A/PR/8/34 H1N1), respiratory syncytial virus (RSV), human rhinovirus type
      14 (HRV 14), coxsackie virus B3 (CVB3) and adenovirus type 7 (AdV-7) in vitro in
      cell culture. Arbidol was found to present potent inhibitory activity against
      enveloped and non-enveloped RNA viruses, including FLU-A, RSV, HRV 14 and CVB3
      when added before, during, or after viral infection, with 50% inhibitory
      concentration (IC50) ranging from 2.7 to 13.8 microg/ml. However, arbidol showed
      selective antiviral activity against AdV-7, a DNA virus, only when added after
      infection (therapeutic index (TI) = 5.5). Orally administered arbidol at 50 or
      100 mg/kg/day beginning 24 h pre-virus exposure for 6 days significantly reduced
      mean pulmonary virus yields and the rate of mortality in mice infected with FLU-A
      (A/PR/8/34 H1N1). Our results suggest that arbidol has the ability to elicit
      protective broad-spectrum antiviral activity against a number of human pathogenic
      respiratory viruses.

PMID- 17497239
TI  - From atoms to proteins.
AB  - The investigation of biological macromolecules and the characteristics that
      determine their function has been of particular interest over the last decades.
      Here we overview some modern approaches for making the most of the 3-D protein
      structural information, with a distinctive emphasis on macromolecular
      crystallography and complementary techniques used to establish the structure
      function relationship. A tight link between the biology of the cellular processes
      and the underlying chemistry of protein function governs the flow of the
      presented material. The reader will be lead through the basic principles of
      protein structure analysis and the means to capture the characteristics that
      portray the function. The techniques exploiting high-resolution data and allowing
      quantification of molecular motion and structure-activity relationship are given
      particular attention.

PMID- 17497240
TI  - Sea urchin embryo as a model for analysis of the signaling pathways linking DNA
      damage checkpoint, DNA repair and apoptosis.
AB  - DNA integrity checkpoint control was studied in the sea urchin early embryo.
      Treatment of the embryos with genotoxic agents such as methyl methanesulfonate
      (MMS) or bleomycin induced the activation of a cell cycle checkpoint as evidenced
      by the occurrence of a delay or an arrest in the division of the embryos and an
      inhibition of CDK1/cyclin B activating dephosphorylation. The genotoxic treatment
      was shown to induce DNA damage that depended on the genotoxic concentration and
      was correlated with the observed cell cycle delay. At low genotoxic
      concentrations, embryos were able to repair the DNA damage and recover from
      checkpoint arrest, whereas at high doses they underwent morphological and
      biochemical changes characteristic of apoptosis. Finally, extracts prepared from
      embryos were found to be capable of supporting DNA repair in vitro upon
      incubation with oligonucleotides mimicking damage. Taken together, our results
      demonstrate that sea urchin early embryos contain fully functional and
      activatable DNA damage checkpoints. Sea urchin embryos are discussed as a
      promising model to study the signaling pathways of cell cycle checkpoint, DNA
      repair and apoptosis, which upon deregulation play a significant role in the
      origin of cancer.

PMID- 17497241
TI  - Human and yeast zeta-crystallins bind AU-rich elements in RNA.
AB  - Zeta-crystallins constitute a family of proteins with NADPH:quinone reductase
      activity found initially in mammalian lenses but now known to be present in many
      other organisms and tissues. Few proteins from this family have been
      characterized, and their function remains unclear. In the present work, zeta
      crystallins from human and yeast (Zta1p) were expressed, purified and
      characterized. Both enzymes are able to reduce ortho-quinones in the presence of
      NADPH but are not active with 2-alkenals. Deletion of the ZTA1 gene makes yeast
      more sensitive to menadione and hydrogen peroxide, suggesting a role in the
      oxidative stress response. The human and yeast enzymes specifically bind to
      adenine-uracil rich elements (ARE) in RNA, indicating that both enzymes are ARE
      binding proteins and that this property has been conserved in zeta-crystallins
      throughout evolution. This supports a role for zeta-crystallins as trans-acting
      factors that could regulate the turnover of certain mRNAs.

PMID- 17497242
TI  - Ginkgo biloba extract EGb 761 increases endothelial nitric oxide production in
      vitro and in vivo.
AB  - Beneficial effects of Ginkgo biloba on peripheral arterial occlusive disease have
      been repeatedly shown in clinical trials, especially after use of EGb 761, a
      standardized special extract. Since the underlying mechanisms are widely unknown,
      we aimed to elucidate the molecular basis on which EGb 761 protects against
      endothelial dysfunction in vitro and in vivo. Application of therapeutically
      feasible doses of EGb 761 for 48 h caused endothelial nitric oxide (NO)
      production by increasing endothelial nitric oxide synthase (eNOS) promoter
      activity and eNOS expression in vitro. Phosphorylation of eNOS at a site typical
      for Akt (Ser 1177) was acutely enhanced by treatment with EGb 761, as was Akt
      phosphorylation at Ser 478. Furthermore, the extract caused acute relaxation of
      isolated aortic rings and NO-dependent reduction of blood pressure in vivo in
      rats. These influences on eNOS represent a putative molecular basis for the
      protective cardiovascular properties of EGb 761.

PMID- 17497244
TI  - Galectins: matricellular glycan-binding proteins linking cell adhesion,
      migration, and survival.
AB  - Galectins are a taxonomically widespread family of glycan-binding proteins,
      defined by at least one conserved carbohydrate-recognition domain with a
      canonical amino acid sequence and affinity for beta-galactosides. Because of
      their anti-adhesive as well as pro-adhesive extracellular functions, galectins
      appear to be a novel class of adhesion-modulating proteins collectively known as
      matricellular proteins (which include thrombospondin, SPARC, tenascin, hevin, and
      disintegrins). Accordingly, galectins can display de-adhesive effects when
      presented as soluble proteins to cells in a strong adhesive state. In this
      context, the de-adhesive properties of galectins should be considered as
      physiologically relevant as the proadhesive effects of these glycan-binding
      proteins. This article focuses on the roles of mammalian galectins in cell
      adhesion, spreading, and migration, and the crossregulation of these functions.
      Although careful attention should be paid when examining individual galectin
      functions due to overlapping distributions, these intriguing glycan-binding
      proteins offer promising possibilities for the treatment and intervention of a
      wide variety of pathological processes, including cancer, inflammation, and
      autoimmunity.

PMID- 17497243
TI  - COMMD proteins: COMMing to the scene.
AB  - COMM Domain-containing or COMMD proteins are a recently discovered group of
      factors defined by the presence of a unique motif in their extreme carboxy
      termini (Copper metabolism MURR1, or COMM domain). This protein family is
      comprised of ten members which are widely conserved throughout evolution and
      share certain functional properties. At the present time, a number of seemingly
      discrete functions have been ascribed to these factors. These include the
      regulation of such events as the activity of the transcription factor NF-kappaB,
      copper homeostasis, the function of the epithelial sodium channel, and cell
      proliferation. A unifying mechanism that would explain all these events is
      lacking at the moment, but recent studies suggest that regulation of the
      ubiquitin pathway may be the basis of many of the functions of the COMMD protein
      family.

PMID- 17497245
TI  - Selectivity determinants of the aldose and aldehyde reductase inhibitor-binding
      sites.
AB  - Aldose reductase and aldehyde reductase belong to the aldo-keto reductase
      superfamily of enzymes whose members are responsible for a wide variety of
      biological functions. Aldose reductase has been identified as the first enzyme
      involved in the polyol pathway of glucose metabolism which converts glucose into
      sorbitol. Glucose over-utilization through the polyol pathway has been linked to
      tissue-based pathologies associated with diabetes complications, which make the
      development of a potent aldose reductase inhibitor an obvious and attractive
      strategy to prevent or delay the onset and progression of the complications.
      Structural studies of aldose reductase and the homologous aldehyde reductase in
      complex with inhibitor were carried out to explain the difference in the potency
      of enzyme inhibition. The aim of this review is to provide a comprehensive
      summary of previous studies to aid the development of aldose reductase inhibitors
      that may have less toxicity problems than the currently available ones.

PMID- 17497246
TI  - Cultural consonance and psychological distress: examining the associations in
      multiple cultural domains.
AB  - Cultural consonance is the degree to which individuals, in their own beliefs and
      behaviors, approximate widely shared cultural models. In previous research in
      Brazil and the United States we found that higher cultural consonance in the
      cultural domains of lifestyle and social support was associated with lower
      psychological distress. The aim of this paper is to expand on these results in
      two ways. First, the measurement of cultural consonance has been improved through
      a closer link of cultural domain analyses and survey research. Second, the number
      of domains in which cultural consonance has been examined has been expanded to
      include-along with lifestyle and social support-family life, national identity,
      and food. We found that cultural consonance in these five domains can be
      conceptualized as two latent variables of generalized cultural consonance, and
      that this generalized cultural consonance is associated with lower psychological
      distress. These results continue to support the usefulness of cultural consonance
      as a theoretical construct in the explanation of human social suffering.

PMID- 17497247
TI  - Chromosomal evolution of Arvicolinae (Cricetidae, Rodentia). I. The genome
      homology of tundra vole, field vole, mouse and golden hamster revealed by
      comparative chromosome painting.
AB  - Cross-species chromosome painting has become the mainstay of comparative
      cytogenetic and chromosome evolution studies. Here we have made a set of
      chromosomal painting probes for the field vole (Microtus agrestis) by DOP-PCR
      amplification of flow-sorted chromosomes. Together with painting probes of golden
      hamster (Mesocricetus auratus) and mouse (Mus musculus), the field vole probes
      have been hybridized onto the metaphases of the tundra vole (Microtus oeconomus).
      A comparative chromosome map between these two voles, golden hamster and mouse
      has been established based on the results of cross-species chromosome painting
      and G-banding comparisons. The sets of paints from the field vole, golden hamster
      and mouse identified a total of 27, 40 and 47 homologous autosomal regions,
      respectively, in the genome of tundra vole; 16, 41 and 51 fusion/fission
      rearrangements differentiate the karyotype of the tundra vole from the karyotypes
      of the field vole, golden hamster and mouse, respectively.

PMID- 17497248
TI  - Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli
      Opitz syndrome (SLOS).
AB  - Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome caused by deficiency
      of 7-dehydrocholesterol reductase catalysing the last step of cholesterol
      biosynthesis. This results in an accumulation of 7- and 8-dehydrocholesterol (7 +
      8-DHC) and, in most patients, a deficiency of cholesterol. Current therapy
      consists of dietary cholesterol supplementation, which raises plasma cholesterol
      levels, but clinical effects have been reported in only a few patients.
      Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors were shown to
      reduce 7 + 8-DHC levels and increase cholesterol concentrations in two small
      trials with divergent clinical outcome. This retrolective study evaluates the
      effects of cholesterol only and of cholesterol plus the HMG-CoA reductase
      inhibitor simvastatin on plasma sterols in 39 SLOS patients and on anthropometric
      measures in 20 SLOS patients. Cholesterol as well as additional simvastatin
      decreased the plasma (7 + 8-DHC)/cholesterol ratio. However, the mechanism
      leading to the decreasing ratio was different. Whereas it was due to an
      increasing cholesterol concentration in the cholesterol-only cohort, a decreasing
      7 + 8-DHC concentration was demonstrated in the cohort receiving additional
      simvastatin. We could not confirm a positive effect of simvastatin treatment on
      anthropometric measures or behaviour, as previously reported.

PMID- 17497249
TI  - [Sudden cardiac death in apparently healthy individuals].

PMID- 17497250
TI  - Channelopathies: a new category of diseases causing sudden death.
AB  - Identification of familial forms of different diseases has provided a unique
      opportunity to study how changes in the structure of a gene create a dysfunction
      in the physiology of the resulting protein. Changes in the genes encoding for ion
      channels produce modifications in the function of the channel. Changes in the
      sodium channel are responsible for long QT syndrome, Brugada syndrome and
      conduction defects. Changes in the potassium channels have been related to long
      QT syndrome, short QT syndrome and familial atrial fibrillation. Relating genetic
      modification and dysfunction allows to study the substrate for a disease,
      understand the physiopathologic mechanism and look for appropriate therapies.

PMID- 17497251
TI  - The Brugada syndrome: facts and controversies.
AB  - The diagnosis of Brugada syndrome (BS) is based on a combination of clinical
      (malignant arrhythmias presenting as syncopal or sudden death episodes) and
      electrocardiographic (pathognomonic ST segment elevation morphology) features.
      Over the last 15 years, since its introduction as a distinct clinical entity, the
      BS has been extensively investigated worldwide. In this article an overview of
      recent developments concerning the genetic background, the diagnostic tools and
      the therapeutic alternatives will be presented. In the last years, the results of
      the first medium-term follow-up studies have also been published. Some of these
      studies present contradictory results, especially concerning the identification
      of useful sudden death predictors in asymptomatic patients. The review presented
      here will discuss this prognostic controversy and will offer possible
      explanations for the different results.

PMID- 17497252
TI  - [Congenital long QT syndrome].
AB  - The long QT syndrome is characterized by prolongation of the heart rate-corrected
      QT interval on the electrocardiogram and by the occurrence of life-threatening
      ventricular tachyarrhythmias of the torsade de pointes type. In most cases, the
      disorder becomes clinically manifest during childhood. Before these events,
      affected patients are typically considered healthy because no other symptoms
      occur. Sudden cardiac death without preceding syncope is rare. The diagnosis is
      based on the patient's history and the evaluation of the surface
      electrocardiogram. Genetic analysis is a relatively new diagnostic tool. The
      disease-causing gene can be identified in approximately 70-80% of patients.
      Symptomatic patients are treated with a beta-blocker. Implanted cardioverter
      defibrillators appear to be the most effective therapy for high-risk patients.
      High-risk patients are defined as those with aborted cardiac arrest or recurrent
      cardiac events (e. g., syncope or torsade de pointes) despite conventional
      therapy (i. e., beta-blocker alone).

PMID- 17497253
TI  - [Short QT syndrome].
AB  - Short QT syndrome is a new genetic disorder associated with familial atrial
      fibrillation and/or sudden death or syncope. To date, different mutations in
      genes encoding for cardiac ion channels (KCNH2, KCNQ1, and KCNJ2) have been
      identified to cause the short QT syndrome. The mutations lead to a gain of
      function of the affected current (IKr, IKs, and IK1). The phenotype is
      characterized by a shortened QT interval<335 ms after correction for heart rate
      at rates<80 beats/min. Furthermore, the QT interval poorly adapts to heart rate.
      Patients exhibit shortened atrial and ventricular effective refractory periods
      and, in the majority, inducibility of ventricular fibrillation. Death occurs
      already in newborns. Therapy of choice seems to be the implantable cardioverter
      defibrillator because of the high incidence of sudden death. Pharmacological
      treatment has been studied and it could be demonstrated, that some mutant
      currents may be insufficiently suppressed by drugs targeted to block the specific
      current such as, e.g., sotalol or ibutilide in patients with a mutation in the
      IKr-coding gene KCNH2 (HERG). Quinidine proved to be efficient in prolonging the
      QT interval and normalizing the effective refractory periods in some patients.

PMID- 17497254
TI  - Catecholaminergic polymorphic ventricular tachycardia.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly lethal
      form of inherited arrhythmogenic disease characterized by adrenergically mediated
      polymorphic ventricular tachycardia. The mutations in cardiac ryanodine receptor
      and calsequestrin genes are responsible for the autosomal dominant and recessive
      variants of CPVT, respectively. The clinical presentation encompasses exercise-
      or emotion-induced syncopal events and a distinctive pattern of reproducible,
      stress-related, bidirectional ventricular tachycardia in the absence of both
      structural heart disease and a prolonged QT interval. The mortality rate in
      untreated individuals is 30-50% by age 40. Clinical evaluation by exercise stress
      testing and holter monitoring and genetic screening can facilitate early
      diagnosis. beta-adrenergic blockers are the most effective pharmacological
      treatment in controlling arrhythmias in CPVT patients, yet about 30% of patients
      still experience cardiac arrhythmias and eventually require an implantable
      cardioverter defibrillator.

PMID- 17497256
TI  - Left ventricular outflow tract tachycardia including ventricular tachycardia from
      the aortic cusps and epicardial ventricular tachycardia.
AB  - Idiopathic outflow tract ventricular tachycardia (VT) can arise from the right
      (RVOT) or left ventricular outflow tract (LVOT). The electrocardiographic (ECG)
      pattern of RVOT VT is typical in most patients, showing a monomorphic left bundle
      branch block (LBBB) QRS morphology with an inferior axis. Radiofrequency catheter
      ablation can be performed with a high success rate and provides a curative
      therapeutic approach. However, not all VTs with LBBB and inferior axis can be
      ablated from the RVOT. It has become apparent that LVOT VTs including VT
      originating from the aortic sinus of Valsalva or epicardium represent
      underrecognized VT entities which are also amenable to successful catheter
      ablation. Twelve-lead ECG criteria can contribute to distinguish between sites of
      VT origin.LVOT arrhythmias represent an increasingly recognized VT entity which
      can be safely and successfully treated by catheter ablation. Identification of VT
      origin using ECG criteria and differentiation of LVOT versus RVOT origin is
      essential in the careful planning of the ablation strategy.

PMID- 17497255
TI  - Idiopathic outflow tract tachycardias: current perspectives.
AB  - Outflow tract ventricular tachycardias (OT-VTs) re the most common form of
      idiopathic VTs. In>80-90% of cases OT-VT originates from the right ventricular
      outflow tract, however, other origins like the septum, the left ventricular
      outflow tract, the pulmonary artery, the aortic sinus of Valsalva, the area near
      the His bundle, and the epicardial surface of the ventricles have been described.
      OT-VT is a diagnosis by exclusion, i.e., the possible concomitant structural
      heart disease should be adequately explored and ruled out in all patients
      presenting with OT-VT. Ablation should be recommended for all patients who
      present with syncope and who also remain symptomatic despite optimal medical
      therapy with a well-tolerated drug.

PMID- 17497257
TI  - Idiopathic ventricular fibrillation.
AB  - Idiopathic ventricular fibrillation (IVF) is responsible for a sizable part of
      sudden cardiac death (SCD). Furthermore, it has a high recurrence rate. Recent
      publications have shown that IVF is often caused by premature ventricular
      contractions (PVCs) arising from the right ventricular outflow tract (RVOT) or
      the Purkinje system. Some cases are associated with unbalanced sympathetic
      cardiac innervation. Some other cases are now believed to be a variant of the
      Brugada syndrome. Drugs have been shown to be ineffective in the therapy of IVF.
      The implantable cardioverter defibrillator used to be the only effective
      therapeutic option. However, radiofrequency (RF) catheter ablation of the trigger
      (PVCs arising from the RVOT or Purkinje system) has shown to be effective in a
      considerable number of patients and is now included in the guidelines of
      secondary prevention of SCD.

PMID- 17497258
TI  - [Development of the Fontan procedure as therapeutic concept for children with
      complex congenital heart disease].
AB  - The spectrum of congenital heart defects reaches from very simple to extremely
      complex anomalies. 3 decades earlier, the prognosis of children with
      univentricular heart defects was poor. The Fontan procedure has been offered to
      patients with a variety of complex cyanotic heart diseases and has resulted in
      decreased mortality. This review summarizes the development and modifications of
      the Fontan procedure. The advances in preoperative, intraoperative und
      postoperative patient management have resulted in greatly improved survivals for
      even the most complex congenital defects. Over the past 3 decades, the survival
      of infants with critical congenital heart defects has increased to 90%.

PMID- 17497259
TI  - [Acute bilateral pulmonary thromboembolism after radical retropubic
      prostatectomy: pulmonary thrombectomy as a "last-chance"-procedure].

PMID- 17497260
TI  - Genetics of tension-type headache.
AB  - The objective of this study was to investigate the importance of genetics in
      tension-type headache. A MEDLINE search from 1966 to December 2006 was performed
      for "tension-type headache and prevalence" and "tension-type headache and
      genetics". The prevalence of tension-type headache varies from 11 to 93%, with a
      slight female preponderance. Co-occurrence of migraine increases the frequency of
      tension-type headache. A family study of chronic tension-type headache suggests
      that genetic factors are important. A twin study analysing tension-type headache
      in migraineurs found that genetic factors play a minor role in episodic tension
      type headache. Another twin study analysing twin pairs without co-occurrence of
      migraine showed a significantly higher concordance rate among monozygotic than
      same-gender dizygotic twin pairs with no or frequent episodic tension-type
      headache, while the difference was minor in twin pairs with infrequent episodic
      tension-type headache. Frequent episodic and chronic tension-type headache is
      caused by a combination of genetic and environmental factors, while infrequent
      episodic tension-type headache is caused primarily by environmental factors.

PMID- 17497261
TI  - A pilot methodological validation study for a population-based survey of the
      prevalences of migraine, tension-type headache and chronic daily headache in the
      country of Georgia.
AB  - We report the methodology of an epidemiological survey of the prevalences of
      migraine, tension-type headache and chronic daily headache in Georgia. Medical
      residents visited adjacent households in Tbilisi to interview a pre-defined
      target of 100 biologically unrelated subjects. All respondents reporting headache
      in the previous year, as well as random 20 non-headache controls, were examined
      by a neurologist. The response rate was 70%. Of 156 respondents, 93 were
      biologically unrelated and 45 (48%) reported headache in the previous year. Eight
      subjects fulfilled all IHS criteria for migraine (1-year prevalence 8.6% [95% CI:
      2.9-14.3%]), and 13 had probable migraine, meeting all but the criterion for
      duration. Nineteen had tension-type headache (20.4% [95% CI: 12.2-28.6%]) and
      five had chronic daily headache (5.4% [95% CI: 1-10.0%]). In comparisons of
      diagnoses by questionnaire and neurologist (considered the gold standard),
      sensitivities for the questionnaire of 89% for migraine and 67% for tension-type
      headache were calculated (overall kappa=0.74).

PMID- 17497262
TI  - Contractile responses to ergotamine and dihydroergotamine in the perfused middle
      cerebral artery of rat.
AB  - The vasomotor effects of ergotamine and dihydroergotamine (DHE) on the middle
      cerebral artery (MCA) of rats were studied using the pressurised arteriography
      method and in vitro myographs. MCAs from Sprague-Dawley rats were mounted on two
      glass micropipettes using the arteriograph, pressurised to 85 mmHg and luminally
      perfused. All vessels used attained spontaneous contractile tone (34.9+/-1.8% of
      resting tone) and responded to luminal adenosine triphosphate (ATP) with
      dilatation (24.1+/-4.0%), which showed functioning endothelium. Luminally added
      ergotamine or DHE induced maximal contractions of 16.8+8% and 22.4+/-0.9%,
      respectively, compared to the resting diameter, with a pEC(50) of 8.7+/-0.1 for
      ergotamine and 9.0+/-0.1 for DHE. Abluminal application of ergotamine and DHE
      also caused concentration-dependent contractions of the perfused MCA by 21.4+/
      2.1% and 23.1+/-7.0%, respectively, with pEC(50) values of 7.6+/-0.2 for
      ergotamine and 8.4+/-0.5 for DHE. The responses were blocked by the 5-HT(2A)
      receptor antagonist ketanserin (concentration 10(-12) to 10(-5) M) and partially
      with the 5-HT(1B) receptor antagonist BRL-11557PM-B. The 5-HT(1D) receptor
      antagonist SB-224289-A had no significant effect. Using a myograph technique,
      isolated ring segments of the MCA with intact endothelium were mounted on two
      metal wires. Neither agonist caused relaxation of resting vessels, however, they
      both responded by weak contractile responses (26+/-3% of submaximal contractile
      capacity relative to 60 mM potassium). The contractions were typically slow in on
      and off set (about 30-60 min). The long duration of ergots should be investigated
      further in an attempt to design drugs with less recurrence.

PMID- 17497263
TI  - Effect of daily migraine prevention on health care utilisation in an insured
      patient population.
AB  - The economic benefits of daily migraine prevention have been subject to ongoing
      debate. This study was undertaken to determine if the initiation of prevention
      had an observable effect on ambulatory health care utilisation when compared to
      acute migraine treatment alone. Administrative claims data from the Military
      Health System were used to conduct a retrospective, longitudinal cohort study of
      3762 patients with migraine. New users of daily migraine prevention were matched
      to a reference group of non-users using propensity score methods. This matched
      sample then was used to evaluate the effect of prevention on ambulatory health
      care expenditures. The study results showed that exposure to daily migraine
      prevention led to lower rates of utilisation relative to what new patients would
      have consumed in the absence of treatment. The results suggest that additional
      economic benefits could be realised by increasing the appropriate use of daily
      migraine prevention.

PMID- 17497264
TI  - SUNCT and high nocturnal prolactin levels: some new unusual characteristics.
AB  - SUNCT is a rare condition characterised by a short-lasting periorbital pain
      associated with autonomic symptoms and is usually unresponsive to pharmacological
      treatment. We report a case of SUNCT syndrome linked to a pituitary micro
      adenoma, with only nocturnal attacks. The nocturnal levels of prolactin (PRL)
      were increased, while other hormonal, haematological, serological and biochemical
      investigations and levels of PRL did not reveal abnormal findings during the day
      time. PRL serum secretion after thyrotropin-releasing hormone test was lower than
      nocturnal secretion, but not enough to induce severe attacks. We suggest that in
      our patient the rise of nocturnal levels of PRL could have a direct role in the
      worsening of this headache, perhaps secondarily to an altered regulation of the
      hypothalamic-hypophysial axis, however the actual influence of sleep and the
      interaction between all neurotransmitters and hormones needs to be clarified
      further.

PMID- 17497265
TI  - Is migraine with cranial nerve palsy an ophthalmoplegic migraine?
AB  - Ophthalmoplegic migraine (OM) is a rare form of primary headache. Because of its
      rarity, only a few cases, mostly symptomatic, are reported. We analyse nine cases
      among 52 973 adults who suffer from headaches with an oculomotor palsy firstly
      considered as OM. The study was retrospective and multicentric in a database set
      up in France. The aim of our investigation was to describe the clinical and
      radiological aspects of these cases and to discuss the diagnosis of OM. We
      demonstrate that the characteristics of the headaches were identical to usual
      migraine without oculomotor nerve palsy for each case. The study emphasises the
      difficulty of the OM diagnosis even with the new IHS criteria because of the
      rarity of having all characteristics. A wide heterogeneity was noted in cranial
      imagery and blood tests. We suggest adding the code of probable OM in the IHS
      classification to increase the knowledge and detection of this type of headache.
      A biological blood test and an MRI are systematically required to help clinicians
      in their diagnosis and to exclude alternative aetiology of headache with palsy.

PMID- 17497266
TI  - A case of posterior scleritis: differential diagnosis of ocular pain.
AB  - Posterior scleritis is a rare cause of ocular pain, due to scleral inflammation,
      presenting with periocular pain, pain on movement and decreased vision. Although
      anterior scleritis may be associated with this condition, ocular signs may be
      absent. We report a case of posterior scleritis, presenting with right-sided
      ocular and periocular pain, exacerbated by ocular movements, irradiating to the
      ipsilateral temple and zygoma, not associated with visual disturbances at onset.
      Diagnosis was made with ultrasonography and confirmed by brain and orbital MRI.
      Differential diagnosis of facial pain, in particular, affecting the periorbital
      region, is discussed. In the presence of ocular pain, even in the absence of
      ocular signs, an ophthalmologic consultation should be performed.

PMID- 17497267
TI  - Acute pharmacotherapy of migraine, tension-type headache, and cluster headache.
AB  - In most migraine patients acute therapy is needed. Migraine can be treated either
      with specific drugs, the triptans and ergot alkaloids, or with NSAIDs. Triptans
      are a major step foreward in migraine therapy. The therapeutic gain for headache
      relief is 50% for subcutaneous sumatriptan whereas it is 30-40% for most oral
      triptans. After oral triptans sustained pain free is only 30%. There is thus
      still ample room for improvement of acute therapy in migraine. For tension-type
      headache there is no specific therapy and it is treated with NSAIDs. Only 17-32%
      become pain free after these drugs. For attacks of cluster headache oxygen and
      subcutaneous sumatriptan can be used. Intranasal triptans can be an alternative.

PMID- 17497268
TI  - Red forehead dot syndrome and migraine.

PMID- 17497269
TI  - Nummular headache: another case treated with gabapentin.

PMID- 17497270
TI  - Early treatment of juvenile migraine reduces disability with disease modification
      implications.

PMID- 17497271
TI  - Migraine with aura and restless legs syndrome.

PMID- 17497272
TI  - Role of intravenous levetiracetam in status migrainosus.

PMID- 17497273
TI  - Comparison of cell deaths induced by transmembrane and secretory TNF-alpha.
AB  - Our previous study showed that transmembrane TNF-alpha (TM-TNF-alpha) had broader
      tumoricidal spectrum than secretory TNF-alpha (s-TNF-alpha). This study examined
      the difference between the two kinds of TNF-alpha in inducing cells and the
      relationship between the apoptosis induced by TM-TNF-alpha and the cell cycle.
      Bioassay was employed to compare the cytotoxic effect of two kinds of TNF-alpha
      on cell lines L-929 and HepG2. TUNEL was used to detect apoptosis and the TdT and
      PI co-staining were used for determining the phase of apoptotic cells. Our
      results showed that TM-TNF-alpha could kill not only s-TNF-sensitive L929 cells
      but also s-TNF-tolerant HepG2 cells. TM-TNF-alpha predominantly induced apoptosis
      while s-TNF could induce both apoptosis and necrosis. The apoptosis of L-929
      cells induced by TM-TNF-alpha mainly occurred in S phase and the apoptosis of
      HepG2 predominantly took place in G(1) phase. It is concluded that the cytotoxic
      effects of the two TNF differ substantially. Since TM-TNF-alpha works locally,
      mainly induces apoptosis and has broader anti-tumor spectrum, it may be more
      effective for the treatment of tumor than s-TNF.

PMID- 17497274
TI  - Anti-angiogeneic target therapy for cancer with vaccine based on the recombinant
      chicken FGFR-1 in tumor-bearing mice.
AB  - To explore the anti-tumor effect of immunotherapy with recombinant protein
      vaccine based on FGFR-1 of chicken (cFR-1) in a mouse Meth A fibrosarcoma model,
      tumor volume and survival rate of the mice were observed at a 3-day interval.
      Microvessel density (MVD) was detected by immunohistochemistry. Auto-antibodies
      against self-FGFR-1 were detected by Western blotting and ELISA, respectively.
      The anti-FGFR-1 antibody-producing B cells (APBCs) were detected by enzyme-linked
      immunospot (ELISPOT) assay. Eighteen days after inoculation of tumor cells, the
      tumor volume was significantly smaller in cFR-1-immunized group than in mouse
      FGFR-1 (mFR-1) immunized group and normal saline (NS) control group (P<0.05), and
      the survival time was significantly longer in cFR-1-immunized group than in the
      control groups (P<0.01). MVD was significantly lower in cFR-1-immunized group
      than in mFR-1-immunized group and NS group (16.8+/-5.6 vs 64.6+/-1.8 and 59.6+/
      8.7, P<0.01). Antibodies against self-FGFR-1 were found in mFR-1-immunized group,
      the major antibody subclasses were IgG1 and IgG2b. Compared with the two control
      groups, the numbers of APBCs in cFR-1-immunized group were significantly
      increased (P<0.01) These results demonstrated that the cFR-1-related anti
      angiogenesis protein vaccine could induce the production of auto-antibodies
      against self-FGFR-1, which futher inhibit angiogenesis and growth of solid tumor.

PMID- 17497275
TI  - Stable expression of Hantavirus H8205 strain G1/IL-2 gene and immune protection
      of the fusion gene.
AB  - To explore the feasibility of stable expression of Hantavirus H8205 strain G1
      segment and human IL-2 fusion gene in Vero cells, and to examine the immune
      protection effects on mice vaccinated with this recombinant eukaryotic expression
      vector containing Hantavirus G1 gene and IL-2 gene. With the help of
      lipofectamine, the Vero cells were transfected with pcDNA3.1/HisB-IL-2-G1 and the
      positive cells were selected by G418. IFAT and SDS-PAGE electrophoresis were used
      to determine the stable transfection and expression of recombinant protein. Each
      mouse was inoculated with plasmids intramuscularly (i.m.) three times, 2 boosts
      were given at 2-week intervals, serum anti-hantavirus antibodies were detected by
      ELISA and neutralizing antibodies (NAb) were detected by Plaque Reduction
      Neutralization Test. The fusion protein expressed in Vero cells was 78 kD,
      corresponding to the estimated molecular size. The neutralizing antibody titers
      of mice with pcDNA3.1/HisB-IL-2-G1 were 1:20-1:80. IL-2/G1 fusion gene could be
      transferred in Vero cells and stably express the fusion protein. Specific humeral
      immune responses in mice can be induced with the recombinant eukaryotic
      expression vector containing the fusion gene, which lays the foundation for
      further development of therapeutic HTNV vaccine.

PMID- 17497276
TI  - Enhancement of immunological activity of CpG ODN by chitosan gene carrier.
AB  - To investigate the enhancement of immunological activity of CpG ODN by chitosan
      gene carrier in mice, the effect of lymphocyte proliferation was detected in mice
      by using MTT, the levels of IgG and cytokines (IL-2 and IL-12) in serum were
      measured by ELISA and peripheral blood T lymphocyte subsets CD4(+), CD8(+) were
      analyzed by flow cytometry. Our results showed that spleen lymphocytes isolated
      from the CS-CpG ODN group of mice showed the strongest proliferation (SI=1.551),
      and the levels of IgG, IL-2 and IL-12 in serum were higher than those of other
      groups. Compared with the immunization with CpG ODN, the immunization with CS-CpG
      ODN gene carrier was more efficient in up-regulating the percentage of CD4(+)T
      cells and the ratio of CD4(+)/CD8(+) of mice. It was concluded that CS gene
      carrier of CpG ODN was much more effective in improving immunity of CpG ODN in
      mice.

PMID- 17497277
TI  - Effect of interleukin-1beta on I(A) and I(K) currents in cultured murine
      trigeminal ganglion neurons.
AB  - To investigate the effect of interleukin-1beta (IL-1beta) on I(A) and I(K)
      currents in cultured murine trigeminal ganglion (TG) neurons, whole-cell patch
      clamp technique was used to record the I(A) and I(K) currents before and after 20
      ng/mL I(L)-1beta perfusion. Our results showed that 20 ng/mL IL-1beta inhibited
      I(A) currents (18.3 +/- 10.7)% (n=6, P<0.05). I(L)-1beta at 20 ng/mL had no
      effect on G-V curve of I(A) but moved the H-infinity curve V0.5 from -36.6+/-6.1
      mV to -42.4+/-5.2 mV (n=5, P<0.01). However, 20 ng/mL IL-1beta had effect on
      neither the amplitude nor the G-V curve of I(K). IL-1beta was found to
      selectively inhibit I(A) current in TG neurons and the effect may contribute to
      hyperalgesia under various inflammatory conditions.

PMID- 17497278
TI  - Effect of Radix Isatidis on the expression of moesin mRNA induced by LPS in the
      tissues of mice.
AB  - To investigate the effect of the anti-endotoxic part of Radix Isatidis on the
      expression of moesin mRNA in murine tissues induced by lipopolysaccharide (LPS),
      the sample solution of F(022) part from Radix Isatidis was intraperitoneally
      administered to experimental mice, and the lipopoly-saccharide (LPS) were
      injected into the tail vein, and then the tissues of liver, kidney and spleen
      were colleted and cut into slices. The mRNA was detected by moesin mRNA
      hybridization in situ. The staining results were observed under microscope. It
      was found that moesin mRNA expression was increased in the tissues of liver,
      kidndy and spleen in mice treated with LPS, while in the mice pre-treated with
      F(022) part from Radix Isatidis, the LPS-induced moesin mRNA expressions in these
      tissues were inhibited in a dose-dependant manner. Our study showed that F(022)
      part from Radix Isatidis can inhibit the LPS-induced expression of moesin mRNA in
      the tissues of liver, kidney and spleen in mice.

PMID- 17497279
TI  - Effects of Andrographitis Paniculata extracts on the expression of CD40 in
      endothelial cells.
AB  - In order to investigate the expression of CD40 in endothelial cells (ECs) in a
      variety of injured conditions and the interventional role of Andrographitis
      Paniculata isolate (API(0134)), the thoracic aorta ECs of guinea pigs were
      cultured in vitro until the third passage, incubated in the presence of media
      containing xanthine oxidase (XO) and xanthine (Xan) which produced oxygen free
      radical (OFR group); oxidized-LDL (ox-LDL group); XO, Xan and API(0134)
      (OFR+API(0134) group); or ox-LDL and API(0134) (ox-LDL+API(0134) group). The
      expression of CD40 in ECs was detected by immunofluorescence assay and reverse
      transcription-PCR (RT-PCR). The results showed as compared with the control
      group, the expression of CD40 in ECs in OFR group and ox-LDL group was increased
      (P<0.01), but attenuated significantly in OFR+ API(0134) group and ox
      LDL+API(0134) group (P<0.05). It was suggested that API(0134) could protect
      atherosclerosis by inhibiting the expression of CD40 molecule in injured ECs.

PMID- 17497280
TI  - Evaluation on the safety and efficacy of tirofiban in the treatment of acute
      coronary syndrome.
AB  - To evaluate the safety and efficacy of tirofiban, a specific inhibitor of the
      platelet glycoprotein llb/llla receptor, in the treatment of unstable angina and
      myocardial infarction without persistent ST elevation (acute coronary syndrome,
      ACS), a total of 200 patients were randomly assigned to a heparin group and a
      tirofiban+heparin group on double-blind basis and the treatment effects of the
      two protocols on ACS were compared when the patients of both groups were taking
      aspirin at the same time. The composite primary end-point events consisted of
      death, myocardial infarction, or refractory ischemia. Our results showed that the
      frequency of the composite primary end point events in 30 days was lower in
      tirofiban+heparin group as compared with that of heparin group (13.9% vs 29.3 %,
      P=0.010). The rates of the other composite end point events in the
      tirofiban+heparin group were also lower than those in the heparin group in 4.5
      days and in 30 days. Bleeding complication occurred in 7.0% of the patients
      receiving heparin alone and in 12.7% of the patients receiving tirofiban and
      heparin in combination (P=0.1717). The study showed that the incidence of
      ischemic events in patients with ACS receiving tirofiban+heparin was lower when
      compared with that of patients who received only heparin and aspirin, suggesting
      that tirofiban might be of special value in the treatment of ACS.

PMID- 17497281
TI  - Irradiation injury temporarily induces enhancement of APN/CD13 peptidase activity
      on aorta-gonads-mesonephros (AGM)-derived stromal cells.
AB  - This study was designed to investigate the expression of aminopeptidase N
      (APN)/CD13 on intraembryonic AGM stromal cells, and the change of its enzymatic
      activity after irradiation injury. The expression of APN/CD13 on AGM stromal
      cells was assayed by RT-PCR and immunohistochemistry. After the stromal cells in
      AGM region were irradiated with 8.0 Gy of (60)Co gamma-rays, APN/CD13 enzymatic
      activity was measured by spectrophotometer at different time points. The result
      showed that AGM stromal cells strongly expressed APN/CD13. The enzymatic activity
      of APN/CD13 decreased temporarily after irradiation injury, then increased to
      higher level 4 h after irradiation, and it returned to the pre-irradiation level
      24 to 48 h after the irradiation. The enzymatic activity of APN/CD13 was
      temporarily enhanced after irradiation injury, which might be one of the
      compensatory mechanisms that promote the hematopoietic recovery after
      irradiation.

PMID- 17497282
TI  - Anti-cancer effects of deguelin on human leukemia K562 and K562/ADM cells In
      Vitro.
AB  - In order to investigate the anti-cancer effects of deguelin and on K562 and
      K562/ADM cells in vitro and the underlying molecular mechanism and compare the
      cytotoxicity of deguelin on K562, K562/ADM cells and human peripheral blood
      mononuclear cells (PBMCs). The effects of deguelin on cell proliferation were
      assessed by MTT assay. Apoptosis were detected by Annexin V/PI double-labeled
      cytometry. The effects of deguelin on the cell cycle were studied by a propidium
      iodide method. Our study showed that deguelin inhibited the proliferation of K562
      cell and K562/ADM cell in a time- and dose-dependent manner and had minimal
      effects on normal human peripheral blood mononuclear cells. The ratio of IC(50)
      value of deguelin of 24 h on K562/ADM cells to K562 cells was only 1.27, which
      was significantly lower than the ratio of IC(50) value of ADM (higher than 20).
      Deguelin could induce apoptosis of K562 cells and K562/ADM cells. K562 cells were
      arrested at G(2)/M phase while K562/ADM cells were arrested at G(0)/G(1) phase.
      Our results suggested that deguelin was a novel anti-leukemia agents with high
      efficacy and low toxicity and it is also a promising agent for reversing drug
      resistance.

PMID- 17497283
TI  - The effects of protein kinase C (PKC) on the tension of normal and passively
      sensitized human airway smooth muscle and the activity of voltage-dependent
      delayed rectifier potassium channel (Kv).
AB  - The effects of protein kinase C (PKC) on the tension and the activity of voltage
      dependent delayed rectifier potassium channel (K(y)) were examined in normal and
      passively sensitized human airway smooth muscle (HASM), by measuring tones and
      whole-cell patch clamp techniques, and the K(v) activities and membrane potential
      (E (m)) were also detected. The results showed that phorbol 12-myristate 13
      acetate (PMA), a PKC activator, caused a concentration-dependent constriction in
      normal HASM rings. The constriction of the passively sensitized muscle in asthma
      serum group was significantly higher than that of the normal group (P<0.05), and
      the constrictions of both groups were completely abolished by PKC inhibitor Ro31
      8220 and calcium channel inhibitor nifedipine. K(v) activities of HASM cells were
      significantly inhibited by PMA, and the E (m) became more positive, as compared
      with the DMSO (a PMA menstruum)-treated group (P<0.01). This effect could be
      blocked by Ro31-8220 (P<0.01). It was concluded that activation of PKC could
      increase the tones of HASM, which might be related to the reduced K(v) activity.
      In passively sensitized HASM rings, this effect was more notable.

PMID- 17497284
TI  - Serum level of vascular endothelial growth factor in patients with obstructive
      sleep apnea hypopnea syndrome.
AB  - To explore the relationship between the serum vascular endothelial growth factor
      (VEGF) level and the severity of obstructive sleep apnea hypopnea syndrome
      (OSAHS), the concentrations of serum VEGF in 40 OSAHS patients and 9 healthy
      controls were measured by using ELISA method. Meanwhile the correlation between
      the concentration of VEGF and parameters of polysomnography (PSG) was examined.
      Our results showed that the concentrations of VEGF were significantly higher in
      OSAHS patients with severe hypoxia (536.8+/-334.7 pg/mL) than in those with mild
      hypoxia (329.2+/-174.7 pg/mL) and healthy controls (272. 8+/-211.0 pg/mL) (P<0.05
      for both). The concentrations of VEGF were also significantly higher in OSAHS
      patients with hypertension (484.5+/-261.4 pg/mL) than in those without
      hypertension (311.0+/-158.4 pg/mL) and healthy controls (272. 8+/-211.0 pg/mL)
      (P<0.05 for both). There was a positive correlation between the concentration of
      VEGF and the apnea hypopnea index (AHI) (r=0.34, P<0.05). It is concluded that
      the concentration of the serum VEGF is positively related to the severity of
      OSAHS. The elevated serum VEGF level may be involved in the pathogenesis of the
      complications of obstructive sleep apnea hypopnea syndrome.

PMID- 17497285
TI  - Expression of c-met stimulated by high glucose in human renal tubular epithelial
      cells and its implication.
AB  - The expression of c-met stimulated by high glucose in human renal tubular
      epithelial cells and the role of HGF/c-met system in diabetic nephropathy were
      examined. The proximal tubular epithelial cells were cultured in vitro under
      different conditions. MTT was used for the detection of cellular proliferation
      and RT-PCR was employed for measurement of c-met mRNA level. Our results showed
      that under different conditions, there were no significant differences in the
      proliferation of proximal tubular epithelial cells 12 h and 24 h after the
      culuture (P>0.05). The proliferation of proximal tubular epithelial cells showed
      a significant change 96 h after the culture and the cellular proliferation
      induced by hepatocyte growth factor (HGF) was very active (P<0.05). Moreover, no
      significant difference in the expression of c-met mRNA was found 12 h after the
      culture under different conditions (P>0.05), while 24 and 96 h after the culture,
      a persistent and significantly higher expression of c-met mRNA was found in HGF
      induced proliferation. It is concluded that addition of exogenous HGF could
      inhibit the apoptosis induced by high-level glucose, promote the proliferation of
      proximal tubular epithelial cells, and induce the expression of c-met. Our study
      suggests that local up-regulation of HGF/c-met system plays an important role in
      the repair of renal damage in diabetic nephropathy.

PMID- 17497286
TI  - Construction and identification of human tissue kallikrein gene eukaryotic
      expressing vector.
AB  - To clone and sequence the human tissue kallikrein gene of Chinese, and to
      construct eukaryotic expression recombinant of KK, total RNA was extracted from
      human pancreas and human tissue kallikrein gene cDNA was amplified by PCR after
      reverse-transcription by using Oligo(dT) primer. The original kallikrein cDNA was
      recovered and filled with Klenow enzyme and inserted into KS plasmid. After
      restriction endonuclease digestion, KK cDNA was sequenced by ABI377 analyzer.
      Then the KK gene was amplified from pBluescript KSKK and inserted into pcDNA3. A
      sequence comparison showed that the cloned kallikrein gene was only one
      nucleotide different from that reported in the Genbank. The coding amino acid was
      Asp in the Genbank gene, while the coding amino acid of Chinese kallikrein gene
      was Asn. The KK cDNA fragment was inserted into the eukaryotic expression vector
      pcDNA3. The cloned kallikrein gene and the pcDNA3KK can be used for further study
      in gene therapy.. .

PMID- 17497287
TI  - The effect of HBx gene on the apoptosis of hepatic cells.
AB  - To study the effect of HBx gene on the apoptosis of the cell lines (L02, HepG2)
      and the interaction between HBx and X-linked inhibitor of apoptosis protein
      (XIAP), the apoptosis of pcDNA3.1-HBx transiently transfected cell lines (L02,
      HepG2) was detected by flow cytometry and the mRNA expression of XIAP was assayed
      by real-time RT-PCR. Our study showed (1) the morphology of L02/pcDNA3.1-HBx was
      changed and the appearance of the cells mimicked that of HepG2 cells; (2) HBx
      gene could be detected in L02/pcDNA3.1-HBx and HepG2/ pcDNA3.1-HBx; (3) the
      apoptosis rate of L02/pcDNA 3.1-HBx was higher than that of L02 cells (P<0.01)
      and the apoptosis rate of HepG2/pcDNA3.1-HBx was lower than that of HepG2 cells
      (P<0.05); (4) the XIAP expression in L02 was about 3 times that in L02/pcDNA3.1
      HBx cells (P<0.01), and the expression of XIAP in HepG2/pcDNA3.1-HBx was about 4
      times that in HepG2 (P<0.01). It is concluded that HBx gene may promote the
      apoptosis of normal hepatocytes and inhibit the apoptosis of cells of hepatic
      carcinoma by regulating the expression of XIAP.

PMID- 17497288
TI  - Effect of tumor necrosis factor-alpha on acyl coenzyme A: cholesteryl
      acyltransferase activity and ACAT1 gene expression in THP-1 macrophages.
AB  - In order to explore the effect and mechanisms of tumor necrosis factor-alpha (TNF
      alpha) on the activity of the acyl coenzyme A: cholesteryl acyltransferase
      (ACAT), THP-1 monocytes were cultured and induced to differentiate into
      macrophages with phorbol ester. TNF-alpha (60 ng/mL) was added at different time
      points into the macrophage-containing medium and the ACAT enzyme activity was
      measured by quantifying the incorporation of [1-(14)C] oleoyl CoA into
      cholesteryl esters. The expression of ACAT-1 protein and mRNA was respectively
      detected by Western blotting and RT-PCR in THP-1 macrophages 24 h after treatment
      with TNF-alpha (60 ng/mL). The results indicated that ACAT activity in THP-1
      macrophages treated with TNF-alpha was increased in a time-dependent manner. The
      expression levels of ACAT-1 protein and mRNA were significantly increased in THP
      1 macrophages after treatment with TNF-alpha (P<0.05). It was suggested that TNF
      alpha could increase the activity of ACAT in THP-1 macrophages by up-regulating
      the expression of ACAT-1 gene.

PMID- 17497290
TI  - Follow-up study on the motion range after treatment of degenerative disc disease
      with the Bryan cervical disc prosthesis.
AB  - This study examined effect of a new intervertebral cervical disc prosthesis in
      relieving the neurological symptoms and signs, improving the patients' ability to
      perform daily activities, reducing pain, and maintaining the stability and
      segmental motion. From December 2003 to October 2004, 12 patients, who had
      received 14 replacements of cervical artificial discs, were followed-up for 2 to
      8 months (with a mean of 5.2 months). Of them 5 had cervical spondylotic
      myelopathy and 7 had cervical disc herniation. The patients included 7 males and
      5 females, with their age ranging from 35 to 62 y and a mean of 50.3 y. Single
      level replacements were performed in 10 cases and 2 cases received two-level
      replacement. Operation time of the single-level surgery averaged 130+/-50 min and
      the time of two-level surgery was 165+/-53 min on average (from skin incision to
      skin suturing). Neurological or vascular complications during or after surgery
      was not observed. Japanese Orthopedic Association scores (JOA scores) increased
      from 8.6 to 15.8 on average. There was no prothesis subsidence or excursion.
      Replaced segments were stable and the range of motion was partially restored,
      being 4.68 degrees (3.6 degrees -6.1 degrees ) in flexion and extension position
      and 3.51 degrees (2.5 degrees -4.6 degrees ), 3.42 degrees (2.6 degrees -4.3
      degrees ) in left and right bending position. No obvious loss of physiological
      curvature was noted. CT or MRI follow-up showed that excursion was less than 1.5
      mm) in 2 of 14 levels and between 1.5 mm and 3 mm) in 1 of 14 levels. No
      ossification in the replaced levels was observed. It is concluded that
      satisfactory short-term results were achieved in the 12 cases of artificial disc
      replacements. Different from anterior cervical discectomy and fusion, the
      replacement could achieve quick functional recovery and did not lead to the
      movement limitation of cervical vertebrae. At least a 5-years follow-up was
      needed to assess the long-term effect of the prosthesis on its neighboring
      segments.

PMID- 17497289
TI  - The roles of four multi-drug resistance proteins in hepatocellular carcinoma
      multidrug resistance.
AB  - The roles of multi-drug resistance protein 1 (MDR1), multi-drug resistance
      related protein 1 (MRP1), lung resistance protein (LRP) and breast cancer
      resistance protein (BCRP) in the multi-drug resistance (MDR) of hepatocellular
      carcinoma (HCC) were studied. By exposing HepG2 cell line to progressively
      increased concentrations of adriamycin (ADM), HepG2 multi-drug resistant subline
      (HepG2/ADM) was induced. The MDR index of HepG2/ADM was detected by using MTT.
      The expressions of the four MDR proteins in the three cell lines (L02, HepG2,
      HepG2/ADM) were investigated at mRNA and protein levels by real-time RT-PCR and
      Western blot respectively. Our results showed that when the ADM concentration was
      under 100 microg/L, HepG2 could easily be induced to be drug-resistant. The
      IC(50) of the HepG2/ADM to ADM was 282 times that of HepG2. The expression of
      MDR1 and BCRP mRNA in HepG2/ADM cells were 400 and 9 times that of HepG2 cells
      respectively while there was no difference in the mRNA expressions of MRP1 and
      LRP. There was no difference between HepG2 and L02 cells in the mRNA expressions
      of the four genes. At the protein level, the expressions of MDR1, BCRP and LRP
      but MRP1 in HepG2/ADM were significantly higher than those of HepG2 and L02.
      Between HepG2 and L02, there was no difference in the expressions of four genes
      at the protein level. HepG2/ADM is a good model for the study of MDR. The four
      genes are probably the normally expressed gene in liver. The expressions of MDR1
      and BCRP could be up-regulated by anti-cancer agents in vitro. The MDR of HCC was
      mainly due to the up-regulation of MDR1 and BCRP but MRP1 and LRP. These findings
      suggest they may serve as targets for the reversal of MDR of HCC.

PMID- 17497291
TI  - Experimental research on ectopic osteogenesis of BMP2-derived peptide P24
      combined with PLGA copolymers.
AB  - To experimentally evaluate the ectopic osteogenetic capacity of synthesized BMP2
      derived peptide P24 combined with poly lactic-co-glycolic acid (PLGA), Wistar
      rats were divided into two groups: group A, in which BMP2-derived peptide
      P24/PLGA complex was implanted, and group B which received simple PLGA implant.
      The complex was respectively implanted into the back muscles of rats. Samples
      were taken the 1st, 4th, 8th, and the 12th week after the implantation. Their
      bone formation was detected by X-ray examination, and tissue response was
      histologically observed. Western blotting was used for the detection of the
      expression of collagen I (Col-I) and osteopontin (OPN). There was acute
      inflammation in the tissue around both types of implants at early stage. The
      cartilage was found around implant areas 4 weeks after the implantation of BMP2
      derived peptide p24/PLGA complex, 8 weeks after the implantation, osteoblasts
      were found, and 12 weeks after the implantation, typical trabecular bone
      structure was observed. In group B, after 12 weeks, no osteoblasts were found. It
      is concluded that PLGA is an ideal scaffold material for bone tissue engineering.
      BMP2-derived peptide can start endochondral ossification and is more effective in
      inducing ectopic osteogenesis.

PMID- 17497292
TI  - Role of caspase-3 inhibitor in induced anoikis of mesenchymal stem cells in
      vitro.
AB  - By preventing mesenchymal stem cells (MSCs) from adhering to precoated agarose to
      create a model of MSC suspension in vitro, we investigated anoikis in MSCs and
      the role of caspase-3 in the anoikis. The cultured MSCs were randomly divided
      into 3 groups: the anoikis group, caspase-3 inhibitor group and control group.
      Before experiment, we coated dishes with 1.5 % agarose; in the anoikis group,
      MSCs were put into the precoated dishes; and in the inhibitor group, caspase-3
      inhibitor and MSCs were also put into the precoated dishes; but there were not
      intervention in the control group. MSCs were collected at 2 h, 6 h, 12 h and 24
      h. The alteration of caspase-3 activity was evaluated by caspase-3 fluorometric
      assay and western blot analysis. The apoptosis rates were detected by flow
      cytometry. MSCs were round and suspended sufficiently in the anoikis and
      inhibitor groups. Caspase-3 fluorometric assay showed that there were significant
      differences in statistics between the anoikis group and the others (P<0.05).
      Western blot analysis discovered that caspase-3 expression in the anoikis group
      was more than that in the control and inhibitor groups (P<0.05). Flow cytometry
      showed that the apoptosis peak appeared in all the three groups, but it increased
      dramatically in the anoikis group. The apoptosis rates in the inhibitor and
      control groups were low and stable. And there were significant differences in
      statistics between the anoikis group and the others (P<0.05). MSCs will undergo
      anoikis in suspended condition if they are separated from the extracellular
      matrix. Caspase-3 inhibitors can suppress caspase-3 activity and reduce the
      apoptosis rate significantly. Caspase-3 plays a vital part in induced MSC anoikis
      in vitro. MSCs suspension culture system might be set up with argorose and
      caspase-3 inhibitor.

PMID- 17497293
TI  - Favorable effect of local VEGF gene injection on axonal regeneration in the rat
      sciatic nerve.
AB  - This study is to investigate the effect of local phVEGF(165) injection on sciatic
      nerve regeneration in the rats and to search for a new way in the further
      treatment of peripheral nerve injuries. Forty-five adult male Wistar rats
      received a neurotomy to bilateral sciatic nerves, which were subsequently
      reconnected with 10/0 epineurial nylon sutures. The injured segments was locally
      injected with normal saline (group A), or 25 microg of phVEGF(165) (group B) or
      50 microg phVEGF(165) (group C). Nerve conduction and regeneration were evaluated
      in terms of the histological changes, weight of gastrocnemius muscles,
      electrophysiology and morphometric results. Our study demonstrated that rats of
      group C showed the best results in terms of nerve regeneration, followed by group
      B and group A. Our findings suggested that local injection of phVEGF165 can
      facilitate nerve regeneration and promote functional recovery in a dose-dependent
      manner.

PMID- 17497294
TI  - Cloning and identification of frc gene from Oxalobacter frmigenes.
AB  - The cloning and identification of frc gene from Oxalobacter formigenes in the
      intestines of Chinese people were conducted. The genomic DNA of Oxalobacter
      formigenes was extracted. frc gene fragment was amplified by polymerase chain
      reaction (PCR) and linked with pEGFP-C1. The recombinant plasmid was designated
      pEGFP-frc and was identified by restriction-enzyme digestion and sequencing.
      Human embryo kidney 293 cells were transfected with pEGFP-frc, then RT-PCR and
      Western blotting were performed to detect the expression of frc gene. The length
      of frc gene was found to be 1287 bp, and the homology of nucleotides and amino
      acid residue with the sequence in GenBank was 95.88% and 99.07%. Bright green
      fluorescent light could be observed in 293 cells transfected with the pEGFP-frc.
      frc mRNA and fusion protein FCoAT-EGFP were detected in the cells. It is
      concluded that frc gene cloned from the Oxalobacter formigenes in the intestines
      of Chinese people can be expressed in eucaryotic 293 cells and keep its enzyme
      activity.

PMID- 17497295
TI  - Experimental study on the effect of high-intensity focused ultrasound (HIFU)
      using Sonablate-500 in the ablation of canine prostate.
AB  - To investigate the safety, feasibility and effectiveness of transrectal high
      intensity focused ultrasound (HIFU) in the ablation of canine prostate, 20 dogs
      were divided randomly into 5 groups. Sixteen canine prostates were treated with
      the third-generation transrectal HIFU device (Sonablate-500). Transrectal
      ultrasound images of the prostate and prostatic urethra were observed
      preoperatively and postoperatively. Serial study was performed 30 min, 30 days,
      60 days and 180 days after the therapy. The rectum, periprostatic tissues, and
      prostate were excised en bloc and the tissues were fixed for gross and
      histological analysis. Our results showed that the average maximal diameter of
      prostatic urethra was 0.59+/-0.11 cm before the operation and 2.57+/-0.98 cm 60
      days after the operation. The volume of prostate was 6.5+/-3.12 cm(3) before the
      treatment while the volume was 4.13+/-0.23 cm(3) 60 days after the treatment and
      the differences were statistically significant (P<0.05). Histologically, there
      was a clear demarcation between the necrotic area of the treated tissues and the
      unaffected surrounding tissues. All the necrotic tissues in the targeted zone
      broke off and the prostatic urethra became cavitary 60 days later. The more
      frequent complications were urinary retention and frequency and hematuria. No
      rectal injury occurred during the treatment. It is concluded that the third
      generation transrectal HIFU is capable of destroying prostatic tissue,
      substantially increasing the width of the prostatic urethra without causing
      injury to the adjacent tissues. The risk of postoperative complications
      associated with HIFU was low. HIFU may become a safe, effective and minimally
      invasive alternative for the treatment of prostatic diseases.

PMID- 17497296
TI  - Neodymium:Yttrium Aluminum Garnet laser for mini-percutaneous treatment of upper
      urinary tract stones.
AB  - To observe the efficacy and safety of mini-percutaneous nephrolithotomy with
      Neodymium: Yttrium Aluminum Garnet (Nd-YAG) laser in the treatment for upper
      urinary tract stones, from December 2005 to September 2006, 31 patients with
      renal stones, 15 patients with ureteral stones and 7 patients with renal and
      ureteral stones underwent mini-percutaneous nephrolithotomy with Nd-YAG laser by
      combination of rigid ureteroscope and flexible ureteroscope under B-ultrasound
      guidance. Clinical data including operation time, lithotripsy time, complications
      and stone-free rate were analyzed retrospectively. Our study showed that the
      percutaneous renal access (F14-F18) was successfully established under B
      ultrasound guidance in all cases. Immediate phase: lithotripsy was performed in
      47 cases through single tract, and in one case through two tracts. Delayed phase
      II lithotripsy was done in 5 cases of renal stones. Operation time ranged from 55
      to 180 min with an average time of 100+/-15 min. Lithotripsy time was from 25 to
      135 min and the average lithotripsy time was 65+/-11 min. No severe complications
      occurred in our series. Complex renal stones were cleared in 34 of 38 cases
      (89.5%). All ureteral stones were completely removed in 15 cases (100%). It was
      concluded that mini-percutaneous nephrolithotomy with Nd:YAG laser for the
      treatment of upper urinary tract stones by combination of rigid ureteroscope and
      flexible ureteroscope has the advantages of effectiveness, mini-invasion, shorter
      operative time and safety.

PMID- 17497297
TI  - Expression of angiopoietin-1/-2 in the process of mouse embryo implantation.
AB  - This study examined the expression and distribution of angiopoietin-1/-2 (Ang-1/
      2) in the endometrium of early pregnant mice. The expression of Ang-1/-2 was
      detected by immunohisto-chemical staining and in situ hybridization respectively.
      Computerized image analysis system was used to measure the average optical
      intensity of Ang-1/-2 in endometria at different time points after gestation.
      Mice were randomly divided into 5 groups: control group, D2 group (2 days after
      pregnancy), D4 group (4 days after pregnancy), D6 group (6 days after pregnancy)
      and D8 group (8 days after pregnancy), each containing 15 mice. The results
      showed that the expression of Ang-1 and Ang-2 was very different among 4 groups
      (P<0.01). Immunohistochemical staining revealed that Ang-1 was localized in the
      cytoplasma of stromal cells 2 days after pregnancy (day 2), and in luminal
      epithelial cells on day 4. The protein of Ang-2 was mainly expressed in the
      cytoplasma of glandular epithelia and stromal cells. With gestation time, the
      positive reactions of Ang-1/-2 were stronger in the endometria of the pregnant
      mice (P<0.01). In situ hybridization showed Ang-1 mRNA in stromal cells on day 2.
      Hybridization signal was localized in both stromal cells and vessel epithelial
      cells on day 4; Ang-2 mRNA was expressed in stromal cells and glandular epithelia
      on day 2; high mRNA levels appeared in stromal cells, glandular epithelia and
      vascular endothelia on day 4; an increasing in mRNA expression of Ang-1/-2 was
      observed on day 6 and day 8 (P<0.01). It is suggested that Ang-1/-2 may play an
      important role in the cross-talk between blastocyst and maternal endometrium
      during the process of embryo implantation.

PMID- 17497298
TI  - Expression of TLR9 and its mRNA in the lesions of lichen planus.
AB  - To investigate the role of toll-like receptor 9 (TLR9) in the pathogenesis of
      lichen planus, the expressions of TLR9 and its mRNA in the lesional skin of
      lichen planus were detected by immunohistochemical technique (SP) and RT-PCR. As
      control, normal skin of healthy volunteers was also tested. The
      immunohistochemical study showed that the expression of TLR9 in the lesional skin
      of lichen planus was significantly higher than that in the normal controls. The
      results of RT-PCR showed that both skin lesions and normal controls had TLR9
      expression. In skin lesions, the expression level of TLR9 mRNA was 1.6075+/
      0.0930, which was significantly higher than that in normal controls (P<0.001).
      These findings indicated that up-regulated expression of TLR9 and its mRNA might
      be involved in the pathogenesis of lichen planus.

PMID- 17497299
TI  - Expression of p63 and cyclooxygenase-2 and their correlation in skin tumors.
AB  - To study the expression of p63 and cyclooxygenase-2 (cox-2) in skin tumors and
      evaluate the correlation between p63 and cox-2, the expressions of cox-2 and p63
      were measured by streptavidin-peroxidase complex immunohistochemical technique in
      17 cases of skin squamous cell carcinoma (SCC), 19 cases of Bowen's
      disease(Bowen), 11 cases of actinic keratosis(AK), 12 cases of seborreic
      keratosis(SK) and 13 specimens of normal skin. Our results showed that the
      expression of p63 in skin squamous cell carcinoma, Bowen's disease and actinic
      keratosis were significantly higher than that in seborreic keratosis, while the
      expression of p63 in seborreic keratosis was significantly higher than that in
      normal skin. The expression of cox-2 in skin squamous cell carcinoma, Bowen's
      disease and actinic keratosis were significantly higher than that in seborreic
      keratosis, while no statistical difference was noted in the expression of cox-2
      between seborreic keratosis and normal skin. Cox-2 expression was positively
      correlated with the high p63 expression in malignant skin tumors. The increased
      expression of cox-2 and p63 may play an important role in the development of skin
      tumors and work synergetically in malignant skin tumors.

PMID- 17497300
TI  - Comparison of the effects of three different anti-fungus drugs on Candida
      albicans of murine vaginal mucosa.
AB  - To compare the therapeutic effects of three different anti-fungal drugs (i.e.,
      terbinafine, fluconazole and intraconazole) in the treatment of experimental
      vaginitis caused by Candida albicans (C. albicans) in mice, the fungal vaginitis
      model was established in female ICR mice by intravaginal inoculation of
      suspension of C. albicans after the animal had been pretreated with estradiol.
      Mice were divided at random into different groups and then respectively treated
      with terbinafine, fluconazole and intraconazole given by gastrogavage. The burden
      of the fungus in the vaginal lavage fluids in the mice of the different groups
      was measured dynamically at different time points after the beginning of the drug
      treatment. The fungal burdens in the vaginal lavage fluids taken at different
      time points from the mice treated with terbinafine were significantly higher than
      those taken at corresponding time points from mice treated with fluconazole or
      itraconazole (P<0.01). The fungal burdens in the vaginal lavage fluids taken from
      mice 1 week after the beginning of the treatment with terbinafine remained at a
      relatively high level. A dramatic drop in the fungal burden was noted in the
      vaginal lavage fluids taken on the 2nd day of the treatment from mice treated
      with itraconazole or fluconazole group and the fungal burden on the 3rd day of
      the treatment in these mice were at a very low level, suggesting that fluconazole
      or itraconazole were highly effective for the treatment. However, the difference
      in the therapeutic effect between the two drugs was not significant (P>0.05).
      Itraconazole or fluconazole, but not terbinafine, is very effective for the
      treatment of fungal vaginitis caused by C. albicans in mice.

PMID- 17497301
TI  - Analysis of nine cases of acute thallium poisoning.
AB  - In this study nine cases of thallium poisoning in a series of homicidal poisoning
      were analyzed in order to provide more information concerning thallium poisoning.
      It was found that the most common clinical feature of thallium poisoning was
      peripheral neuropathy and paraesthesia was more common than amyasthenia.
      Understanding of these clinical characteristics of thallium poisoning was helpful
      to early identification and differential diagnosis. Since the early
      administration of Prussian Blue, as a specific antidote for thallium poisoning,
      can substantially improve the prognosis, it is of great importance to establish a
      correct and early diagnosis.

PMID- 17497302
TI  - A case-control study on high-risk factors for newborn hearing loss in seven
      cities of Shandong province.
AB  - To investigate the high-risk factors for newborn hearing loss and to provide
      information for preventing the development of hearing loss and delaying its
      progression, from May 2003 to June 2006, neonates who failed to pass the
      universal newborn hearing screening (UNHS) were referred to Jinan Newborn Hearing
      Screening and Rehabilitation Center from 7 newborn hearing screening centers in
      seven cities of Shandong province. One-to-one pair-matched case-control method
      was employed for statistical analysis of the basic features of definitely
      identified cases. High-risk factors relating to the bilateral hearing loss were
      evaluated by univariate and multivariate Logistic regression analysis. Our
      results revealed that 721 transferred newborns who didn't pass the hearing
      screening received audiological and medical evaluation and 367 were confirmed to
      have hearing loss. Of them, 177 neonates with hearing loss who met the matching
      requirements were included in the study as subjects. Univariate analysis showed
      that high-risk factors related to hearing loss incuded age of father, education
      backgrounds of parents, parity, birth weight, gestational weeks, craniofacial
      deformity, history of receiving treatment in neonatal intensive care unit (NICU),
      neonatal disease, family history of otopathy and family history of congenital
      hearing loss. Multivariate Logistic regression analysis revealed that 4
      independent risk factors were related to bilateral hearing loss, including parity
      (OR=16.285, 95% CI 3.379-78.481), neonatal disease (OR=34.968, 95% CI 2.720
      449.534), family history of congenital hearing loss (OR=69.488, 95% CI 4.417
      1093.300) and birth weight (OR=0.241, 95% CI 0.090-0.648). It is concluded that
      parity, neonatal disease and family history of hearing loss are the promoting
      factors of bilateral hearing loss in neonates and appropriate intervention
      measures should be taken to deal with the risk factors.

PMID- 17497303
TI  - Lipase catalyse glycerolysis for kinetic resolution of racemates.
AB  - Candida antarctica lipase B catalyzed kinetic resolution of representative
      secondary alcohols, esters, and amine was successfully performed using triacetin
      or glycerol as solvents and acyl donor/acceptor. High conversions and
      enantioselectivities were achieved and the product was easily separated by simple
      extraction with diethyl ether.

PMID- 17497304
TI  - Mass spectrometrical analysis of the processed metastasis-inducing anterior
      gradient protein 2 homolog reveals 100% sequence coverage.
AB  - Anterior gradient protein 2 homolog is a metastasis-inducing protein in a rat
      model of rat breast cancer and prognostic for outcome in hormonally treated
      breast cancer patients. Carrying out protein profiling in several mammalian cells
      and tissues, we detected this protein (synonym: secreted cement gland protein XAG
      2 homolog) that was originally described in toad skin, in human bronchial
      epithelia. Tissues obtained from biopsies were homogenised and extracted proteins
      were run on two-dimensional gel electrophoresis. Following in-gel digestion with
      proteases trypsin, AspN, LysC and chymotrypsin, mass spectrometrical analysis was
      carried out by MALDI-TOF/TOF. The use of MS following multi-enzyme digestion of
      the protein resulted into 100% sequence coverage. MS/MS analysis enabled
      sequencing of 87% of the protein structure. This percentage does not include the
      signal peptide that was not observed in our protein due to processing. No
      posttranslational modifications were detectable and no sequence conflicts were
      observed. Complete analysis, unambiguous identification and characterisation of
      this biologically important protein could be shown, which is relevant for the
      definition of a marker protein that has been described so far by immunochemical
      methods only. Complete analysis is of importance as it forms the basis for all
      future work on this protein and, moreover, may serve as an analytical tool for
      further studies.

PMID- 17497305
TI  - A DING phosphatase in Thermus thermophilus.
AB  - Phosphate transport in bacteria occurs via a phosphate specific transporter
      system (PSTS) that belongs to the ABC family of transporters, a multisubunit
      system, containing an alkaline phosphatase. DING proteins were characterized due
      to the N-terminal amino acid sequence DINGG GATL, which is highly conserved in
      animal and plant isolates, but more variable in microbes. Most prokaryotic
      homologues of the DING proteins often have some structural homology to
      phosphatases or periplasmic phosphate-binding proteins. In E. coli, the product
      of the inducible gene DinG, possesses ATP hydrolyzing helicase enzymic activity.
      An alkaline phosphorolytic enzyme of the PSTS system was purified to homogeneity
      from the thermophilic bacterium Thermus thermophilus. N-terminal sequence
      analysis of this protein revealed the same high degree of similarity to DING
      proteins especially to the human synovial stimulatory protein P205, the
      steroidogenesis-inducing protein and to the phosphate ABC transporter,
      periplasmic phosphate-binding protein, putative (P. fluorescens Pf-5). The enzyme
      had a molecular mass of 40 kDa on SDS/PAGE, exhibiting optimal phosphatase
      activity at pH 12.3 and 70 degrees C. The enzyme possessed characteristics of a
      DING protein, such as ATPase, ds endonuclease and 3' phosphodiesterase (3'
      exonuclease) activities and binding to linear dsDNA, displaying helicase activity
      on supercoiled DNA. Purification and biochemical characterization of a T.
      thermophilus DING protein was achieved. The biochemical properties, N-terminal
      sequence similarities of this protein implied that the enzyme belongs to the PSTS
      family and might be involved in the DNA repair mechanism of this microorganism.

PMID- 17497306
TI  - Novel synthesis of alpha-PNA monomers by U-4CR.
AB  - A novel synthesis of alpha-PNA monomers was carried out by U-4CR, followed by
      photochemical cleavage of the 2-nitrobenzyl group and selective hydrolysis in the
      presence of 10% HCl in THF. Three of four functional components in the U-4CR were
      specially protected: cyclohexenyl isocyanide, Boc for protecting the amino group
      of glycine, and 2-nitrobenzyl group as a photocage (photoremovable protecting
      group) for ammonia. The amino group of aldehyde-containing adenine is too weak to
      interfere with the U-4CR, so that it is not necessary to be protected.

PMID- 17497307
TI  - Healthcare worker's perceptions of barriers to care by immigrant women with
      postpartum depression: an exploratory qualitative study.
AB  - OBJECTIVE: We interviewed healthcare workers working in Toronto, Canada,
      regarding their experience of providing care to recent immigrant women suffering
      from postpartum depression. The objective was two-fold: 1) to identify potential
      barriers to care that recent immigrant women may encounter as perceived by
      healthcare workers; and 2) to identify challenges healthcare workers felt that
      they faced as providers of care to this population. METHODS: Qualitative semi
      structured interviews were conducted with 16 key informants from various
      disciplines employed by healthcare agencies providing care to postpartum
      immigrant women in Toronto. Constant comparative analysis was used to analyze the
      data. RESULTS: Two main categories of barriers to care for recent immigrant women
      were identified: 'practical barriers' and 'culturally determined barriers'.
      Practical barriers included knowing where and how to access services, and
      language difficulties. Cultural barriers included fear of stigma and lack of
      validation of depressive symptoms by family and society. The challenges
      experienced by healthcare providers working with this population were organized
      into two other categories: 'professional limitations', and 'social/cultural
      barriers'. 'Professional limitations' included fear of incompetence, language
      barriers, and inadequate assessment tools. 'Social/cultural barriers' included
      the experience of cultural uncertainty. CONCLUSIONS: The results suggest that not
      only are there important barriers to accessing postpartum care for recent
      immigrant women, but it can also be challenging for healthcare workers to deliver
      such needed care. Understanding some of these barriers and challenges from the
      perspective of healthcare providers is an important step to remedying gaps and
      obstacles in the service system.

PMID- 17497308
TI  - Cancer survivorship research: state of knowledge, challenges and opportunities.
AB  - INTRODUCTION: Seminal advances in early detection of and treatment strategies for
      cancer have led to burgeoning numbers of cancer survivors. While most therapeutic
      modalities for cancer are beneficial and lifesaving, they are associated with
      adverse long-term and late sequelae. MATERIALS AND METHODS: Literature review
      using MEDLINE to identify studies examining adverse medical outcomes and post
      treatment follow-up care among long-term survivors. Emerging concepts in
      survivorship research such as definitional issues, research paradigms and
      methodologic concerns were also examined. RESULTS: Long-term or late adverse
      sequelae are more prevalent, serious, and persistent than expected in survivors
      of pediatric and adult cancer, but remain understudied especially among those
      diagnosed as adults. Follow-up care relevant to survivorship outcomes is neither
      standardized nor guideline or evidence based for most adult cancers, and optimal
      practices have yet to be defined. DISCUSSION: Adverse sequelae contribute to
      burden of illness, health care costs, and decreased length and quality of
      survival. To-date, very few studies have compared survivor outcomes pre-and post
      diagnosis. It is critical to examine under-researched questions and understudied
      survivor groups. Regular follow-up care and monitoring of health status post
      cancer treatment should 1) permit the timely diagnosis and treatment of adverse
      outcomes; 2) enable timely diagnosis and treatment of recurrences; 3) facilitate
      screening and early detection of second cancer(s); 4) allow for detection and
      management of co-morbidities; and 5) provide the opportunity for preventive
      strategies such as lifestyle changes. Research findings to-date underscore the
      need for continued cancer survivorship research that will: inform our
      understanding of the mechanisms underlying adverse sequelae; lead to the design
      of less toxic treatments; test the effectiveness of interventions - medical,
      pharmacologic, and behavioral - that reduce adverse outcomes; test models of post
      treatment follow-up care; develop an evidence base for optimal follow-up care
      practices; and inform survivor and provider decision making.

PMID- 17497309
TI  - Follow-up of long-term cancer survivors in the Nordic countries.
AB  - Cancer survivors are at increased risk of developing different co-morbid
      conditions. With an increasing number of long-term cancer survivors in the Nordic
      countries, the need for recommendations for long-term follow-up has become
      necessary. However, at present there are no general guidelines for follow-up in
      the Nordic countries. Three steps of follow-up should be distinguished and the
      objectives associated with each: 1) Follow-up research done as clinical studies
      in cancer survivors and as registry-based epidemiological investigations.
      Whenever possible these approaches should be combined with translational research
      relating clinical observations with findings from biological material for
      increased understanding of pathophysiology and aetiology. Such investigation has
      to provide evidence-based knowledge of late effects associated with the
      malignancy itself and its treatment. The Nordic countries have excellent
      possibilities for conducting such follow-up research; 2) Creation of guidelines,
      in an attempt to put results from research into clinical practice, should take
      the local situation and resources into consideration. Provision of an
      individualized Survivorship Care Plan is a first step; 3) Implementation of
      guidelines into daily health care. Guidelines have little influence on long-term
      cancer care if they do not reach the practitioners and convince them to comply.
      There is a need for well-planned follow-up to manage and reduce possible
      treatment-related morbidity and mortality in cancer survivors. The Nordic
      countries provide excellent possibilities for relevant research, but lack, so far
      evidence-based guidelines. In agreement with the initiatives of ASCO the
      development of Survivor Care Plans is the first step to improve on this
      situation.

PMID- 17497310
TI  - Rehabilitation of cancer patients - research perspectives.
AB  - Rehabilitation of cancer patients include a broad range of activities aimed at
      information, counselling, advices on possible change of lifestyle and behaviour,
      psychological support, social welfare questions, ways of coping with side-effects
      of the anti-carcinogenic treatment given and additional treatment of numerous
      clinical problems. The change in the age distribution combined with the growing
      number of cancer survivors and the scarce economic resources allocated to 'after
      treatment' clinical follow-up of cancer patients, even in the Scandinavian
      countries characterised by their public tax financed health system, emphasize the
      need for screening of rehabilitation needs among cancer patients. There is a need
      to identify patients in need for psychological and social intervention. However,
      this intervention among cancer patients in need has to be based on results
      achieved in clinical studies. This paper gives a brief introduction to the field
      of rehabilitation research and indicates a number of areas in which research
      would be of benefit for the clinical organisation of rehabilitation activities.
      These areas include the implication of social inequality, a characterisation of
      cancer patients who rehabilitate successfully, the gender perspective in
      rehabilitation, the age perspective, how to establish cancer disease specific
      rehabilitation modules, family and community aspects of rehabilitation, the
      dilemma between individual responsibility for lifestyle changes and feelings of
      guilt and the need for models which can determine the best timing of the
      intervention among cancer patients.

PMID- 17497311
TI  - Factors affecting cancer survivors' employment and work ability.
AB  - PURPOSE: Due to the improved prognosis of many forms of cancer, an increasing
      number of cancer survivors are both willing and able to return to work after
      their treatment. This has increased interest in studying work and cancer-related
      issues. The purpose of this paper is to give an overview of research on the
      impact of cancer on employment and work ability, on the effect of psychosocial
      factors on survivors' well-being, and to indicate research needs for the future.
      RESULTS: Studies have shown that the majority of cancer survivors are able to
      continue working. There is, however, a group of cancer survivors who suffer from
      impaired health as a result of their illness, and this impairment sometimes leads
      to a decreased ability to work, or even disability. Employment and impaired work
      ability has most commonly been found to be associated with cancer type, type of
      treatment, health status, education and physical workload. The few studies that
      have focused on the effects of psychosocial factors in work life suggest that
      social support from occupational health services, and workplace accommodations
      for illness affect cancer survivors' return to work. CONCLUSIONS: More research
      is needed on the impact of social factors at work, which seem to play an
      important role in cancer survivors' ability to continue working.

PMID- 17497312
TI  - Stability of health-related quality of life in the Norwegian general population
      and impact of chronic morbidity in individuals with and without a cancer
      diagnosis.
AB  - The stability of Health-Related Quality of Life (HRQoL) in the general population
      (GenPop) over years has rarely been evaluated. Neither has the impact of chronic
      morbidity on HRQoL in cancer survivors been extensively assessed, when identified
      in the Norwegian GenPop. We studied both aspects. HRQoL was evaluated in two
      GenPop surveys in 1996 and 2004 using the EORTC QLQ-C30. The 2004 survey included
      self-reports of a malignant diagnosis and use of medication for hypertension,
      diabetes mellitus and/or anxiety/depression. Comparison of the results from both
      surveys revealed similarity of the HRQoL profiles of the two surveys and
      confirmed the associations between HRQoL and age and gender. Cancer survivors and
      individuals from the GenPop without chronic co-morbidity had similar HRQoL,
      except for poorer physical and role function in cancer survivors (p <0.01). HRQoL
      worsened significantly if a cancer survivor suffered from chronic co-morbidity.
      Multivariate analyses confirmed the associations between HRQoL and chronic common
      co-morbidity in cancer survivors and non-cancer persons. As common chronic co
      morbidity significantly impairs HRQoL in cancer survivors, prevention of adverse
      health conditions represents a major challenge in such survivors. Further, in the
      interpretation of HRQoL in cancer survivors' co-morbid conditions and socio
      demographic variables must be considered. Over an 8 years period the HRQoL of the
      Norwegian GenPop appeared to be stable.

PMID- 17497313
TI  - A review of the impact of photon and proton external beam radiotherapy treatment
      modalities on the dose distribution in field and out-of-field; implications for
      the long-term morbidity of cancer survivors.
AB  - The use of untraditional treatment modalities for external beam radiotherapy such
      as intensity modulated radiation therapy (IMRT) and proton beam therapy is
      increasing. This review focuses on the changes in the dose distribution and the
      impact on radiation related risks for long-term cancer survivors. We compare
      conventional radiotherapy, IMRT, and proton beam therapy based on published
      treatment planning studies as well as published measurements and Monte Carlo
      simulations of out-of-field dose distributions. Physical dose parameters
      describing the dose distribution in the target volume, the conformity index, the
      dose distribution in organs at risk, and the dose distribution in non-target
      tissue, respectively, are extracted from the treatment planning studies. Measured
      out-of-field dose distributions are presented as the dose equivalent as a
      function of distance from the treatment field. Data in the literature clearly
      shows that, compared with conventional radiotherapy, IMRT improves the dose
      distribution in the target volume, which may increase the probability of tumor
      control. IMRT also seems to increase the out-of-field dose distribution, as well
      as the irradiated non-target volume, although the data is not consistent, leading
      to a potentially increased risk of radiation induced secondary malignancies,
      while decreasing the dose to normal tissues close to the target volume, reducing
      the normal tissue complication probability. Protons show no or only minor
      advantage on the dose distribution in the target volume and the conformity index
      compared to IMRT. However, the data consistently shows that proton beam therapy
      substantially decreases the OAR average dose compared to the other two
      techniques. It is also clear that protons provide an improved dose distribution
      in non-target tissues compared to conventional radiotherapy and IMRT. IMRT and
      proton beam therapy may significantly improve tumor control for cancer patients
      and quality of life for long-term cancer survivors.

PMID- 17497314
TI  - Cancer related fatigue: a focus on breast cancer and Hodgkin's disease survivors.
AB  - BACKGROUND AND PURPOSE: Fatigue is one of the most common and troubling symptoms
      in cancer survivors. In this paper we review information about cancer related
      fatigue in survivors of breast cancer and Hodgkin's disease, discuss some of the
      potential biological mechanisms for this problem in cancer survivors, and briefly
      discuss potential interventions. FINDINGS: Cancer-related fatigue persists long
      after cancer treatments end, and is associated with more intensive treatments
      (combined chemotherapy and radiation therapy) in these cancers. Fatigue prior to
      the onset of treatment is a strong predictor of persistent fatigue. Studies in
      breast cancer survivors suggest elevated levels of pro-inflammatory cytokines in
      association with persistent fatigue, as well as abnormalities in the hypothalamic
      pituitary axis. Psychosocial and physical activity interventions have been shown
      in some studies to alleviate fatigue. CONCLUSIONS: Recognizing the syndrome of
      cancer-related fatigue is a high priority for the many cancer survivors who
      continue to experience this complaint as a chronic health problem.

PMID- 17497315
TI  - Gonadal dysfunction and fertility problems in cancer survivors.
AB  - Gonadal dysfunction and fertility problems are adverse effects of cancer
      treatment or may be associated with specific malignancies. This review focuses on
      these problems in the young cancer survivors, where methods of protecting or
      restoring endocrine function and fertility need to be considered. In females,
      treatment adverse effects can result in infertility, but premature ovarian
      failure (POF) is probably relevant for more female cancer survivors, affecting
      also those who do not wish post-treatment parenthood. POF affects present and
      future health, especially through oestrogen deficiency symptoms and an increased
      risk of developing osteoporosis. A lower risk of developing POF has been
      considered in young females than in older due to a larger pool of oocytes.
      However, a recent long-term follow-up study reported a prevalence of POF in young
      females with Hodgkin's lymphoma of 37% showing that young age at time of
      treatment only delays the development of POF. In male gonads, germ cells are much
      more sensitive to irradiation and chemotherapy than Leydig cells. Thus,
      infertility is a more common adverse effect than hypogonadism. Some malignancies
      are particular relevant. Persistent azoospermia was formerly common after
      treatment for Hodgkin's lymphoma, but currently, most patients recover
      spermatogenesis. Modern treatment of childhood acute lymphoblastic leukemia is
      also unlikely to cause infertility. Norwegian testicular cancer survivors
      diagnosed in 1980-1994 who attempted conception had an overall 15-year actuarial
      post-treatment paternity rate of 71% (range 48-92% depending on the treatment).
      However, the rate was significantly higher among men diagnosed in1989-1994 (over
      80%) than in 1980-1988 (about 63%). Patients at risk for hypogonadism and
      infertility should be defined prior to treatment, and available methods for
      gonadal preservation should maximally be utilised. During follow-up, oncologists
      should routinely address these issues.

PMID- 17497316
TI  - Some musculo-skeletal sequelae in cancer survivors.
AB  - This paper deals with some of the musculo-skeletal complication that can occur
      after cancer treatment. In particular, we focus on Cancer Treatment Induced Bone
      Loss (CTIBL) and the musculo-skeletal complications that can occur in patients
      treated for extremity sarcoma. In addition we discuss peripheral neuropathy,
      musculo-skeletal pain and briefly mention some of the complications related to
      radiotherapy. CTIBL is mostly studied in breast cancer and prostate cancer
      survivors. The cause in these groups is mainly due to treatment induced
      hypogonadism. Other causes of CTIBL are indirect or direct cause of chemotherapy,
      physical inactivity and inadequate intake of vitamin D and calcium. Treatment of
      CTIBL consists of diet and lifestyle changes and pharmacological intervention.
      Extremity bone sarcomas constitute a special group since they often experience
      mutilating surgery and heavy combination chemotherapy. The treatment results in
      worse function than the normal population and the amputated usually have lower
      physical functioning than patients treated with limb sparing surgery (LSS).
      However, most studies fail to show differences in quality of life between the
      amputated and LSS. Most of the studies performed on musculo-skeletal sequelae
      have been done on survivors of childhood cancer, breast cancer or prostate
      cancer. More studies among the other cancer groups are needed to reveal the
      extent and prevalence of these complications.

PMID- 17497317
TI  - Late neurological complications after irradiation of malignant tumors of the
      testis.
AB  - To identify and describe late neurological complications in a Danish testis
      cancer cohort treated by radiotherapy. Clinical retrospective material of 94
      consecutive patients with malignant testicular tumours treated at Aarhus County
      Hospital from 1964 to 1973. The irradiated dose in the paraaortic field varied
      from 27 to 55 Gy given 5 or 6 days a week, from the back and front alternately.
      The biological equivalent dose of the spinal cord was calculated using the linear
      quadratic model. Median follow-up was 25 years, range 7 to 33 years. Seven
      patients were identified with late neurological complications after irradiation.
      One developed symptoms 9 months after treatment, but in the six other cases we
      found a latency period between 10 and 20 years from radiotherapy until the
      initial neurological symptoms began. The clinical picture in all seven patients
      was dominated by muscle atrophy, flaccid paresis in the lower limbs and absence
      of sphincter disturbances or sensory symptoms. High spinal cord dose was related
      to increased risk of neurological damage. During follow-up 19 patients developed
      another primary cancer in the radiation field; nine patients were diagnosed with
      severe arteriosclerosis and 13 patients with long-term gastrointestinal
      morbidity. Seven patients were identified with late neurological complications,
      and a clear dose-incidence relationship was shown. The latency period, from
      irradiation to the initial neurological symptoms began, ranged from 9 months to
      20 years with progression of symptoms beyond 25 years. Furthermore many patients
      in the cohort suffered from solid tumours in the radiation field, severe
      arteriosclerosis and long-term gastrointestinal morbidity.

PMID- 17497318
TI  - Late adverse effects of radiation therapy for rectal cancer - a systematic
      overview.
AB  - PURPOSE: The use of radiation therapy (RT) together with improvement in the
      surgical treatment of rectal cancer improves survival and reduces the risk for
      local recurrences. Despite these benefits, the adverse effects of radiation
      therapy limit its use. The aim of this review was to present a comprehensive
      overview of published studies on late adverse effects related to the RT for
      rectal cancer. METHODS: Meta-analyses, reviews, randomised clinical trials,
      cohort studies and case-control studies on late adverse effects, due to pre- or
      postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were
      systematically searched. Most information was obtained from the randomised
      trials, especially those comparing preoperative short-course 5 x 5 Gy radiation
      therapy with surgery alone. RESULTS: The late adverse effects due to RT were
      bowel obstructions; bowel dysfunction presented as faecal incontinence to gas,
      loose or solid stools, evacuation problems or urgency; and sexual dysfunction.
      However, fewer late adverse effects were reported in recent studies, which
      generally used smaller irradiated volumes and better irradiation techniques;
      although, one study revealed an increased risk for secondary cancers in
      irradiated patients. CONCLUSIONS: These results stress the importance of careful
      patient selection for RT for rectal cancer. Improvements in the radiation
      technique should further be developed and the long-term follow-up of the
      randomised trials is the most important source of information on late adverse
      effects and should therefore be continued.

PMID- 17497319
TI  - 15-year prospective follow-up of patient-reported outcomes of late bowel toxicity
      after external beam radiotherapy for localized prostate cancer. A comparison with
      age-matched controls.
AB  - We have previously described patient-reported outcomes of late side effects
      induced by conventional external beam radiotherapy (EBRT), 4 and 8 years after
      treatment, in 181 patients with localized prostate cancer compared with 141 age
      matched controls. In the present study, we compare bowel side effects 15 years
      after EBRT with the same controls, and with the results of our previous 4-year
      and 8-year follow-ups. Of the 181 patients and 141 controls at the 4-year follow
      up, 45 patients (25%) and 79 controls (56%) were still alive at the 15-year
      follow-up. Bowel symptoms were assessed using the symptom-specific questionnaire
      Prostate Cancer Symptom Scale (PCSS), which was sent to these 45 patients and 79
      age-matched controls with a mean follow-up time of 15 years (162-197 months)
      after EBRT. The answer frequency was 64% in the patient group and 52% in the
      control group. The mean age was 78 years in both groups. At the 15-year follow
      up, 39% of the patients and 84% of the controls reported no bowel problems (p <
      0.001), while 16% of the patients and 0% of the controls reported "Quite a
      few/many" problems with mucus in the stools (p < 0.001). "Quite a bit/much" stool
      leakage was reported by 20% of the patients at the 15-year follow-up, in
      comparison to 4% of the patients at the 4-year follow-up (ns). The proportion of
      patients reporting late bowel symptoms was unchanged 15 years after EBRT in
      comparison to the 4-year follow-up. Increased bowel symptoms were seen in
      patients in comparison to the age-matched controls.

PMID- 17497320
TI  - Effect of adjuvant systemic treatment on cosmetic outcome and late normal-tissue
      reactions after breast conservation.
AB  - To investigate whether adjuvant treatment with CMF or tamoxifen predisposes to an
      unfavorable cosmetic outcome or increased breast morbidity after radiotherapy in
      breast conservation. Data from 266 patients who entered a randomized breast
      conservation trial (DBCG-82TM protocol) was analyzed. The patients were treated
      with lumpectomy and axillary dissection followed by external beam radiotherapy to
      the residual breast. High-risk patients (n = 94), as well as 31 low-risk
      patients, received additional radiation to the regional lymph nodes. Adjuvant
      systemic treatment was given to all high-risk patients: premenopausal patients (n
      = 67) received eight cycles of CMF intravenously (600/40/600 mg per m2) every
      fourth week; postmenopausal patients (n = 27) received 30 mg of tamoxifen daily
      for one year. Clinical assessments included cosmetic outcome, breast fibrosis,
      skin telangiectasia, and dyspigmentation which were scored on a 4-point
      categorical scale after median 6.6 years. The observations were analyzed in
      multivariate logistic regression analysis which included potential risk factors
      on outcome related to systemic treatment, surgery, radiation technique, tumor,
      and patient characteristics. In premenopausal patients, systemic treatment with
      CMF independently predicted a fair/poor cosmetic outcome, RR = 2.2 (95% CI 1.2
      4.2), as well as increased skin telangiectasia, RR = 3.3 (1.4-8.2). There was no
      impact of tamoxifen treatment on cosmetic outcome in postmenopausal patients (p =
      0.32). However, univariate analysis showed that tamoxifen was significantly
      associated with breast fibrosis (p < 0.004), as was radiation to the regional
      lymph nodes (p < 0.0001). A strong interaction between axillary irradiation and
      tamoxifen treatment occurred since 26 of 27 high-risk postmenopausal patients had
      received both tamoxifen and axillary irradiation. In multivariate regression
      analysis, axillary irradiation independently predicted moderate/severe breast
      fibrosis with a relative risk of 5.0 (2.0-12.5) and 9.6 (3.3-27.7) in
      premenopausal and postmenopausal patients, respectively. To circumvent the strong
      interaction between tamoxifen treatment and axillary irradiation, a subsequent
      analysis omitting axillary treatment from the multivariate regression showed a
      significant effect of both tamoxifen and CMF on the occurrence of breast fibrosis
      with relative risks of 5.3 (CI 1.8-15.8) and 4.4 (1.8-10.3), respectively.
      Adjuvant systemic treatment with CMF given sequentially to radiotherapy
      independently predicted an adverse cosmetic outcome as well as increased skin
      telangiectasia after breast conserving treatment. Due to a strong interaction
      between tamoxifen administration and radiation to the regional lymph nodes, the
      effect of tamoxifen on the development of fibrosis could not be fully discerned
      in this study. Axillary irradiation increased the incidence of moderate to severe
      breast fibrosis in both premenopausal and postmenopausal patients.

PMID- 17497321
TI  - A controlled study of job strain in primary-treated cancer patients without
      metastases.
AB  - To explore job strain in Norwegian primary-treated cancer survivors compared to
      matched controls from the general population. The study has a cross-sectional,
      matched case-control design. A sample of 417 employed cancer survivors (208
      females with breast cancer and 209 males with testicular or prostate cancer) who
      had been diagnosed 1-5 years prior to the study and were tumor-free rated
      themselves on the Demands-Control-Support Questionnaire (DCSQ). Their ratings
      were compared to those of 417 employed controls from the general population,
      matched with the survivors on time of investigation, gender, age and municipality
      of living. No differences in job strain were observed between cancer survivors
      and controls, or between subgroups of survivors, except that female survivors
      experienced more strain than males. In certain subgroups statistically
      significant differences on the DCSQ were found: older survivors showed higher
      scores on demands than their controls, female survivors reported lower control
      and higher strain than male survivors, and older male survivors felt higher
      demands than younger ones. However, the effect sizes of these differences were so
      small (< 0.20) that they hardly were relevant for the work situation. In
      multivariate analyses survivorship versus control status was not significantly
      associated with any of the DCSQ measures. The job strain of these cancer
      survivors did not differ in any work relevant way from their controls, and
      survivorship status was not significantly associated with job strain. A longer
      follow-up of survivors is necessary in order to draw conclusion about the
      stability of these findings over time.

PMID- 17497322
TI  - The cumulative incidence of gemcitabine-induced thrombotic microangiopathy.

PMID- 17497323
TI  - Cetuximab rescue a patient with non-small cell lung cancer from rapid disease
      progression during chemotherapy.

PMID- 17497324
TI  - High incidence of fistula formation during bevacizumab treatment in rectal cancer
      patients.

PMID- 17497325
TI  - Chronic myelomonocytic leukemia with p190 BCR-ABL rearrangement mimicking
      advanced liver disease at presentation.

PMID- 17497326
TI  - Arsenic trioxide/ascorbic acid therapy in patients with refractory metastatic
      colorectal carcinoma: a clinical experience.
AB  - Arsenic trioxide (As2O3) has demonstrated effectiveness in treating acute
      promyelocytic leukemia (APL). Therefore the FDA has approved it to treat APL. In
      patients with refractory metastatic colorectal carcinoma (CRC), we assessed the
      efficacy and toxicity of As2O3/AA (ascorbic acid) as the outcome of this trial.
      Five patients with refractory metastatic CRC who failed all previous standard
      chemotherapy were enrolled in this study. They were treated with 0.25 mg/kg body
      weight/day As2O3 and 1000 mg/day of ascorbic acid for 5 days a week for 5 weeks.
      Each treatment cycle extended for 7 weeks with 5 weeks of treatment and 2 weeks
      of rest. All the patients developed moderate to severe toxic side effects to
      arsenic trioxide/AA therapy and therefore the study was discontinued. No CR
      (complete remission) or PR (partial remission) was observed. CT scans
      demonstrated stable or progressive disease. Three of the five patients died
      within 2 to 5 months after cessation of the therapy. None of the deaths could be
      related to this clinical trial. Two years of follow-up study showed that two
      patients were alive with stable disease. Under the current treatment regimen all
      patients developed moderate to severe side effects with no clinically measurable
      activity. As an alternate, efforts may be made to reduce the dose and arsenic
      trioxide may be combined with other standard regimen in reversing the chemo
      resistance.

PMID- 17497327
TI  - A trivial sign to rare genetic disorder.

PMID- 17497328
TI  - Comment on: incidence, pattern and timing of brain metastases among patients with
      advanced breast cancer treated with trastuzumab.

PMID- 17497330
TI  - A longitudinal study of environmental Salmonella contamination in caged and free
      range layer flocks.
AB  - The environmental contamination by salmonella was examined over a 12-month period
      in 74 commercial layer flocks from eight farms in the UK, which previously had
      been identified as being contaminated with salmonella. Samples of faeces, dust,
      litter, egg belt spillage and wildlife vectors were taken, plus swabs of cages,
      feeders, drinkers, floors, egg belts and boots. Some sampling was performed in
      each month of the year. Numerous serovars were detected but Salmonella enterica
      serotype Enteritidis was the only persistent serotype found among single-age
      flocks. There was a significant correlation between qualitative environmental
      samples and semi-quantitative faeces samples. The level of environmental
      contamination increased significantly over time. There were significant
      temperature and seasonal effects upon contamination. Wildlife vectors proved to
      be sensitive samples for the detection of salmonella. The efficacy of cleaning
      and disinfection upon residual salmonella contamination, and upon subsequent
      flock contamination, was highly variable between and within premises. The
      variability between detected prevalences over time and between flocks indicates a
      need for regular, sensitive monitoring of flocks for salmonella to permit
      targeting of control measures aimed at eliminating contamination of the layer
      environment by salmonella. There is substantial scope for improvement of cleaning
      and disinfection procedures.

PMID- 17497331
TI  - The Salmonella pathogenicity island 1 and Salmonella pathogenicity island 2 type
      III secretion systems play a major role in pathogenesis of systemic disease and
      gastrointestinal tract colonization of Salmonella enterica serovar Typhimurium in
      the chicken.
AB  - Salmonella enterica serovar Typhimurium infection of chickens is a major public
      and animal health problem. In young chicks, S. Typhimurium infection results in
      severe systemic infection; in older chicks, infection results in prolonged
      gastrointestinal tract colonization. Here we determined the role of the
      Salmonella pathogenicity island 1 (SPI-1) and Salmonella pathogenicity island 2
      (SPI-2) type III secretion systems in systemic infection and gastrointestinal
      tract colonization of the chicken though experimental infection of chicks with a
      S. Typhimurium strain with mutations in the genes encoding the secretion system
      machinery of SPI-1 (spaS) and SPI-2 (ssaU) that prevent secretion of effector
      proteins. In 1-day-old chicks, mutation of SPI-2 lead to a decrease in both
      systemic bacterial numbers and pathology, although no difference in
      gastrointestinal numbers was observed. Mutation of SPI-1 had little effect in 1
      day old chicks. In 1-week-old animals the SPI-2 mutants could not be detected
      systemically and colonized the gastrointestinal tract only in low numbers in
      comparison with the parent strain, and was cleared in 1 week. The SPI-1 mutant
      showed greatly reduced levels of systemic infection, and colonized the
      gastrointestinal tract at a lower level than the parent strain. The findings show
      that the SPI-2 type III secretion system is required for systemic S. Typhimurium
      infection in both infection models, and that it plays a significant role in
      gastrointestinal colonization. The SPI-1 system is involved in both systemic
      infection and gastrointestinal colonization, but does not appear absolutely
      essential for either infection process.

PMID- 17497332
TI  - Experimental evidence for transmission of Mycoplasma gallisepticum in house
      finches by fomites.
AB  - Ever since Mycoplasma gallisepticum emerged among house finches in North America,
      it has been suggested that bird aggregations at feeders are an important cause of
      the epidemic of mycoplasmal conjunctivitis because diseased birds could deposit
      droplets of pathogen onto the feeders and thereby promote indirect transmission
      by fomites. In this paper we bring the first experimental evidence that such
      transmission (bird-to-feeder-to-bird) does actually take place. House finches
      infected via this route, however, developed only mild disease and recovered much
      more rapidly than birds infected from the same source birds but directly into the
      conjunctiva. While it is certainly probable that house finch aggregations at
      artificial feeders enhance pathogen transmission, to some degree transmission of
      M. gallisepticum by fomites may serve to immunize birds against developing more
      severe infections. Some such birds develop M. gallisepticum antibodies, providing
      indication of an immune response, although no direct evidence of protection.

PMID- 17497333
TI  - Prevalence of West Nile virus neutralizing antibodies in colonial aquatic birds
      in southern Spain.
AB  - The rapid expansion of West Nile virus (WNV) throughout the New World has raised
      interest in understanding the population dynamics and patterns of dispersal of
      emerging infectious diseases by wildlife. WNV affects humans, although its main
      reservoirs are various species of birds. Here we analyse the prevalence of WNV
      neutralizing antibodies in nearly full-grown chicks belonging to seven different
      species of colonial waterbirds at three localities in southern Spain. Chicks with
      neutralizing antibodies against WNV were detected in three species and at all
      three localities. However, the low antibody titres suggest the presence of
      antibodies is probably due to maternal transfer of antibody, presumably from
      exposure of the adult birds to WNV or a similar flavivirus at some stage of their
      lives. The analyses of the movements of tagged birds confirmed that all species
      with antibody visit regions that have had reports of WNV infection over the past
      decade.

PMID- 17497334
TI  - Clinical, mycological and pathological findings in turkeys experimentally
      infected by Aspergillus fumigatus.
AB  - Experimental aspergillosis was induced in 1-day-old turkeys by intra-air-sac
      inoculation of a spore suspension of a 3-day-old Aspergillus fumigatus culture
      (CBS 144.89) containing 10(7) spores. Ten additional poults were used as
      controls. Infected and non-infected animals were closely observed at least twice
      a day for the appearance of clinical signs and were sequentially sacrificed at
      days 1, 2, 3, 5 and 7 post-inoculation. In the infected group, most lung tissues
      and air sac swabs were culture positive from day 1 to day 5. At 1 day post
      inoculation, air sac membranes were multifocally and moderately to severely
      thickened by an oedema and covered by an exudate. A small number of germinating
      conidia were present in the superficial exudate, already giving rise to small
      radiating hyphae. Lung lesions were mild, dominated by a diffuse congestion and a
      mild heterophilic infiltration. From 2 to 3 days post-inoculation, air sac
      membranes were more severely affected and several granulomas were observed. Both
      granulomas and exudates were rich in germinated conidia and hyphae. Pulmonary
      lesions consisted in a diffuse pneumonia. Five days post-inoculation, air sac
      membrane lesions progressed to a severe, multifocal, heterophilic and
      granulomatous inflammation. Seven days post-inoculation, a reduction of the
      severity of the diffuse pneumonia was detected. Concomitantly, the fungal
      elements were mainly observed as fragmented tubules in the cytoplasm of
      multinucleate giant cells. The present study demonstrated that healthy turkey
      poults might be able to withstand exposure to 10(7) A. fumigatus spores.

PMID- 17497335
TI  - Epidemiological and pathological studies of subgroup J avian leukosis virus
      infections in Chinese local "yellow" chickens.
AB  - Epidemiological, pathological and molecular studies indicate that subgroup J
      avian leukosis virus (ALV-J) infections are widely spread in "yellow chickens" of
      local breeds in China. ALV-J induced tumour mortality and the serological
      conversion rates to ALV-J were very high in some breeder flocks. Typical
      myelocytomatosis was demonstrated not only in livers, spleens, kidneys, and
      sternums, as in white meat-type chickens, but also in thymuses and the bursa of
      Fabricius. Especially, severe myeloid cell infiltration was found throughout the
      whole enlarged thymuses of some birds. ALV-J was isolated at high positive rates
      from both liver tumour samples and embryos collected from breeder flocks with
      tumours. At the same time, reticuloendotheliosis virus was also co-isolated with
      ALV-J in some tumour samples and embryos. Sequence analysis of env genes
      demonstrated that the gp85 and gp37 among six ALV-J isolates from "yellow
      chickens" of Chinese local breeds varied as highly as among ALV-J strains
      isolated from white meat-type chickens worldwide. But strain GD0512 isolated in
      2005 from a "yellow chicken" farm in southern China had high identity of 95.1%
      for gp85 or 99.5% for gp37 to strain HN0001 isolated in 2000 from a white meat
      type breeder farm in northern China, a much higher identity than to other yellow
      chicken and white chicken strains. This is the first report of the isolation and
      identification of ALV-J from yellow chickens of Chinese local breeds and also the
      first report of vertical co-infection of ALV-J and reticuloendotheliosis virus.
      The significance of co-infection of ALV-J and reticuloendotheliosis virus in
      pathogenesis is discussed.

PMID- 17497336
TI  - Genetic diversity of Gallibacterium isolates from California turkeys.
AB  - The aim of the present study was to investigate the genetic diversity of
      Gallibacterium isolates recovered from lesions in turkeys. Gallibacterium has
      been isolated from various bird species including turkeys, but no large
      investigations have yet been made to characterize isolates from turkeys
      genetically. We therefore genotyped 53 Gallibacterium isolates obtained from
      turkeys between 1998 and 2004. Fifty isolates originated from 29 different flocks
      in California and the remaining three came from three German turkey flocks. All
      were recovered from birds with lesions, mainly in the upper respiratory tract.
      Five chicken isolates from California and five Gallibacterium reference strains
      were also included. Amplified fragment length polymorphism analysis demonstrated
      substantial genetic diversity among the Gallibacterium isolates. However, we also
      demonstrated that some Gallibacterium clones were present in consecutive
      rotations at the same farm during the entire 6-year observation period and were
      present in different flocks from different farms. Similarly, the same clone was
      identified from two of the three German flocks. Further investigation of the
      spread of Gallibacterium between turkey flocks, including infections acquired
      from chickens or wild birds, should be carried out.

PMID- 17497337
TI  - S1 gene sequence heterogeneity of a pathogenic infectious bronchitis virus strain
      and its embryo-passaged, attenuated derivatives.
AB  - Infectious bronchitis virus CK/CH/LDL/97I was attenuated by serial passage in
      chicken embryos. Virus of passage 115 was attenuated as determined by clinical
      response to inoculation to 15-day-old specific pathogen free chickens. The
      vaccination-challenge test showed that the attenuated passage 115 virus could
      afford protection against the homologous pathogenic virus, passage 5, by the
      clinical response. Based on the sequence analysis and comparison of the S1 gene,
      both the pathogenic and attenuated CK/CH/LDL/97I viruses were populations that
      each included at least two subpopulations. Also, from analysis of the amino acid
      and nucleotide sequences of S1 gene, we speculate that recombination between the
      minor and dominant subpopulations plus accumulation of mutations in the S1 region
      of pathogenic passage 5 might lead to the formation of the embryo-passaged,
      attenuated passage 115.

PMID- 17497338
TI  - Investigations on the aetiology of pinching off syndrome in four white-tailed sea
      eagles (Haliaeetus albicilla) from Germany.
AB  - The purpose of this study was to investigate the aetiology of the pinching off
      syndrome (POS), a generalized feather abnormality affecting free-living nestling
      of the white-tailed sea eagle (Haliaeetus albicilla) in Europe. For the first
      time, extensive clinical, haematological, biochemical, virological,
      bacteriological, nutritional, histopathological, parasitological and electron
      microscopical examinations were performed on three females and one male suffering
      from POS. Early and increased cytokeratin formation at the base of regenerating
      feathers and their follicle was observed in affected birds. Ultrathin sections of
      the feather papillae revealed an extended stratum transitivum and a compact,
      thickened keratinized stratum corneum. The transitional cells in POS feathers
      contained vacuoles often associated with the nucleus. Lipofuscin accumulations in
      neurons, glial cells and islet cells of the pancreas were found in all examined
      birds. It was not clear whether there is an association between the occurrence of
      lipofuscin and POS. No evidence was found to suggest that infectious agents
      (parasites, bacteria, fungi or viruses), malnutrition or hormonal imbalances are
      involved in the aetiology of POS in white-tailed sea eagles. It remains unclear
      whether there is a genetic background of POS.

PMID- 17497339
TI  - Pathobiology of highly pathogenic avian influenza virus (H5N1) infection in mute
      swans (Cygnus olor).
AB  - The results of pathological, virological and polymerase chain reaction
      examinations carried out on 35 mute swans (Cygnus olor) that succumbed to a
      highly pathogenic avian influenza virus (H5N1) infection during an outbreak in
      Southern Hungary are reported. The most frequently observed macroscopic lesions
      included: haemorrhages under the epicardium, in the proventricular and duodenal
      mucosa and pancreas; focal necrosis in the pancreas; myocardial degeneration;
      acute mucous enteritis; congestion of the spleen and lung, and the accumulation
      of sero-mucinous exudate in the body cavity. Histopathological lesions comprised:
      lymphocytic meningo-encephalomyelitis accompanied by gliosis and occasional
      perivascular haemorrhages; multi-focal myocardial necrosis with lympho
      histiocytic infiltration; pancreatitis with focal necrosis; acute desquamative
      mucous enteritis; lung congestion and oedema; oedema of the tracheal mucosa and,
      in young birds, the atrophy of the bursa of Fabricius as a result of lymphocyte
      depletion and apoptosis. The observed lesions and the moderate to good body
      conditions were compatible with findings in acute highly pathogenic avian
      influenza infections of other bird species reported in the literature. Skin
      lesions and lesions typical for infections caused by strains of lower
      pathogenicity (low pathogenic avian influenza virus) such as emaciation or
      fibrinous changes in the reproductive and respiratory organs, sinuses and airsacs
      were not observed. The H5N1 subtype avian influenza virus was isolated in
      embryonated fowl eggs from all cases and it was identified by classical and
      molecular virological methods.

PMID- 17497340
TI  - Coronavirus associated with an enteric syndrome on a quail farm.
AB  - An enteric syndrome was observed in quail (Coturnix coturnix) semi-intensively
      reared for restocking in Apulia (southern Italy). The birds showed depression,
      severe diarrhoea, dehydration and reduced growth. Mortality occurred particularly
      in young birds. At necropsy the prominent lesion was enteritis. A coronavirus was
      detected by electron microscopy and reverse transcriptase-polymerase chain
      reaction in the faeces and in the intestinal content of the dead quails. The
      virus could not be cultivated in chicken embryos. By sequence analyses of a
      fragment (409 nucleotides) of region 1b of the polymerase gene, the quail
      coronavirus displayed <or=93% nucleotide identity to avian coronaviruses (group 3
      coronaviruses)--whereas by analysis of the S1 portion of the spike protein
      encoding gene, the quail coronavirus displayed 16% to 18% amino acid identity
      with infectious bronchitis virus, and 79% to 81% identity with turkey
      coronavirus. Altogether, the findings suggest the existence of a novel
      coronavirus genetically related to turkey coronavirus.

PMID- 17497341
TI  - The use of vitamin E in type 2 diabetes mellitus.
AB  - Diabetes mellitus has assumed epidemic proportions in most parts of the world,
      and it is a major source of morbidity in developed countries. In addition, in
      several instances, diabetes is associated with a variety of metabolic
      abnormalities, including abdominal obesity, insulin resistance, hypertension,
      dyslipidemia, and hyperglycemia. There is considerable evidence that
      hyperglycemia causes the generation of reactive oxygen species (ROS), ultimately
      leading to increased oxidative stress in a variety of tissues. In the absence of
      an appropriate compensatory response by the endogenous antioxidants, such as
      vitamins C and E, catalase, glutathione, and superoxide dismutase, oxidative
      stress dominates, resulting in the activation of stress-sensitive intracellular
      signaling pathways. One of the major consequences is the generation of gene
      products that cause cellular damage and are ultimately responsible for the late
      complications of diabetes. The ability of antioxidants to protect against the
      effects of hyperglycemia in vitro, along with the clinical benefits often
      reported following antioxidant therapy, supports a causative role of oxidative
      stress in mediating and/or worsening these abnormalities. This review will focus
      on the critical assessment of the literature as it relates to the association
      between oxidative stress and diabetes, followed by the role of oxidative stress
      in the complications of type 2 diabetes mellitus. Finally, a review of the use of
      the antioxidant vitamin E will be provided in diabetic patients by assessing and
      evaluating some of the clinical trials in the literature.

PMID- 17497342
TI  - Atrial and brain natriuretic peptide and endothelin-1 concentration in patients
      with idiopathic arterial hypertension: the dependence on the selected
      morphological parameters.
AB  - INTRODUCTION: The aim of the work was to study the maintenance of atrial and
      brain natriuretic peptide (ANP, BNP) and endothelin-1 (ET-1) in patients with
      idiopathic arterial hypertension and the relationships between cardiac
      morphological parameters and concentrations of examined peptides in group of
      patients with left ventricular hypertrophy (LVH). METHODS: Seventy-six patients
      were enrolled in the study: 21 patients with confirmed idiopathic arterial
      hypertension (group 1), 18 with idiopathic hypertension and eccentric hypertrophy
      (group 1a), 14 with idiopathic hypertension and concentric hypertrophy (group
      1b), and 23 patients without arterial hypertension, organic heart disease, or
      chronic respiratory tract diseases (group 2 - control group). All subjects were
      submitted for echocardiographic evaluation. Posterior wall thickness (PWT),
      interventricular septum thickness (IVST), left ventricular end-diastolic diameter
      (LVEDd), left atrium diameter (LAD), left ventricular mass index (LVMI), ejection
      fraction (EF), fractional shortening (FS), midwall shortening fraction (MWS), and
      relative wall thickness index (RWT) were studied. Concentrations of ANP(1-28),
      BNP, and ET-1 were determined with the use of radioimmunological kits (RIA). The
      obtained results were subjected to statistical analysis. RESULTS: A considerable
      increase of ANP and BNP was observed in all patients with hypertension (group 1)
      in comparison to patients without hypertension (group 2). Significant increases
      of ANP were found in groups 1a and 1b in comparison to group 1 and 2, as well as
      considerably increase of BNP in group 1b compared to groups 1, 1a, and 2. In the
      group of patients with hypertension (group 1), a significant increase in the
      concentration of ET-1 compared to group 2 was found. However, the concentrations
      of ET-1 in groups 1 and 2 were not statistically different. Significant
      differences in concentrations of ET-1 between groups 1a, 1b, and 1 and 2 were
      seen. Significant correlations were found between concentrations of ANP, BNP, ET
      1 and morphological parameters: PWT, IVST, LVMI and RWT. In group 1b, a
      correlation between concentrations of ANP, BNP, MWS, and LAD was found. The
      multiple regression analysis showed that RWT independently correlates with
      concentrations of ANP and BNP, and the concentration of BNP is in closer relation
      to RWT than ANP. In the case of ET-1, the multiple regression analysis did not
      show that LVMI or RWT had any independent influence on secretion of ET-1 in
      patients with idiopathic hypertension and LVH. CONCLUSIONS: Increased
      concentration of ANP in patients with idiopathic hypertension may point to the
      coexistence of complications with type of LVH. High concentration of BNP may
      specifically suggest concentric LVH. This is important - especially if there are
      difficulties in interpretations of results of other clinical examinations.
      However, increased concentrations of ET-1 in the plasma of patients with
      hypertension and LVH should not be treated as an indicator of LVH degree.

PMID- 17497343
TI  - Basic autonomic nervous function in patients with neurocardiogenic syncope.
AB  - Basic autonomic nervous function was evaluated in patients with neurocardiogenic
      syncope (NCS). Atropine, isoproterenol, propranolol, phenylephrine, and
      phentolamine were administered successively, and parasympathetic nerve activity
      and beta- (and alpha-) activity, sensitivity, and secretion of the sympathetic
      nerve were determined in patients with NCS and control subjects. In patients with
      NCS, beta- and alpha- sensitivity were higher and beta-activity and beta- and
      alpha-secretion lower than in control subjects. In patients with NCS, the
      increased basic beta-sensitivity may contribute to induce strong cardiac
      contractions and augment ventricular mechanoreceptor response, and a compensatory
      state against diminished neuronal sympathetic activity is suggested by the
      increased alpha-sensitivity.

PMID- 17497344
TI  - Orienting-defense responses and psychophysiological reactivity in isolated clinic
      versus sustained hypertension.
AB  - This study sought to determine whether patients with white-coat or isolated
      clinic hypertension (ICH) show, in comparison to patients with sustained
      hypertension (SH), a defense response pattern to novel stimuli and an enhanced
      psychophysiological reactivity to stress. Forty-three patients with essential
      hypertension were divided into two groups after 16 days of self-monitoring blood
      pressure (BP): ICH (24 men; self-measured BP < 135/85 mmHg) and SH (19 men; self
      measured BP >or= 135/85 mmHg). Defense responses were measured as the cardiac
      changes to phasic non-aversive auditory stimuli. Psychophysiological reactivity
      (heart and breath rate, blood volume pulse, electromyography, and skin
      conductance) was measured during mental arithmetic and video game tasks. The
      standard deviation of self-measured BPs and the difference between mean BPs at
      work and at home were used as indicators of cardiovascular reactivity to daily
      stress. No significant differences were seen in defense responses or
      psychophysiological reactivity to laboratory or naturally occurring stressors.
      These results do not support the hypothesis that ICH can be explained in terms of
      a generalized hyperreactivity to novel or stressful stimuli.

PMID- 17497345
TI  - Regulation of renal ouabain-resistant Na+-ATPase by leptin, nitric oxide,
      reactive oxygen species, and cyclic nucleotides: implications for obesity
      associated hypertension.
AB  - This study examined the effect of leptin on renal ouabain-resistant Na(+)-ATPase,
      which drives the reabsorption of about 10% of sodium transported in the proximal
      tubule. Chronic leptin administration (0.25 mg/kg s.c. twice daily for seven
      days) increased Na(+)-ATPase activity by 62.9%. This effect was prevented by the
      coadministration of superoxide dismutase mimetic, tempol, or the NADPH oxidase
      inhibitor, apocynin (2 mM in the drinking water). Acutely administered NO donors
      decreased Na(+)-ATPase activity. This effect was abolished by soluble guanylate
      cyclase inhibitor, ODQ, but not by protein kinase G inhibitors. Exogenous cGMP
      reduced Na(+)-ATPase activity, but its synthetic analogues, 8-bromo-cGMP and 8
      pCPT-cGMP, were ineffective. The inhibitory effect of NO donors and cGMP was
      abolished by EHNA, an inhibitor of cGMP-stimulated phosphodiesterase (PDE2).
      Exogenous cAMP analogue and dibutyryl-cAMP increased Na(+)-ATPase activity and
      abolished the inhibitory effect of cGMP. Finally, the administration of
      superoxide-generating mixture (xanthine oxidase+hypoxanthine) increased Na(+)
      ATPase activity. The results suggest that nitric oxide decreases renal Na(+)
      ATPase activity by stimulating cGMP, which in turn activates PDE2 and decreases
      cAMP concentration. Increased production of reactive oxygen species may lead to
      the elevation of Na(+)-ATPase activity by scavenging NO and limiting its
      inhibitory effect. Chronic hyperleptinemia is associated with increased Na(+)
      ATPase activity due to excessive oxidative stress.

PMID- 17497346
TI  - Abstracts of the 12th International Symposium on SHR--Genetics of Experimental
      and Human Hypertension in Relation with Environmental Factors, October 20-21,
      2006, Kyoto, Japan.

PMID- 17497351
TI  - Suitability of excised rabbit ear skin - fresh and frozen - for evaluating
      transdermal permeation of estradiol.
AB  - Estradiol transdermal application still represents a relevant topic due to the
      recent controversies about hormone replacement therapy, its increasing potential
      in the treatment of skin aging and wound healing, and the new use of its
      derivatives in the transdermal contraceptive treatment. The aim of our work was
      to verify if fresh or frozen rabbit ear skin can be a suitable skin model to
      study in vitro estradiol transdermal absorption. Fresh rabbit ear skin
      demonstrated a reasonable model of human epidermis in the investigation of
      estradiol permeation starting from both solutions and commercial patches.

PMID- 17497352
TI  - Preparation, characterization and pharmacokinetics of liposomes-encapsulated
      cyclodextrins inclusion complexes for hydrophobic drugs.
AB  - Liposomes-encapsulated indomethacin/cyclodextrins (IMC/ CD) inclusion complexes
      were prepared. The characteristics and pharmacokinetics of the combined system
      were investigated. The high drug entrapment values of 2.38 +/- 0.16 microg/mg and
      2.48 +/- 0.12 microg/mg for liposomes-encapsulated IMC/ beta-CD and IMC/HP-beta
      CD inclusion complexes were achieved, as only 1.60 +/- 0.09 microg/mg for
      conventional liposomes. Encapsulating IMC/CD inclusion complexes into liposomes
      resulted in a slow release of drug. Following intravenous administration, both
      liposomes-encapsulated inclusion complexes showed significantly improved AUC(0 -
      infinity) compared with that of conventional liposomes (p < 0.05). After
      intramuscular administration, C(max) has been increased to 5.21 +/- 1.14 microg x
      ml(-1) and 6.02 +/- 1.22 microg x ml(- 1) for liposomes-encapsulated IMC/ beta 
      CD and IMC/HP-beta -CD inclusion complexes, respectively, whereas only 2.43 +/-
      0.69 microg x ml(- 1) for liposomes-encapsulated free drug (p < 0.01).

PMID- 17497353
TI  - Enhancement of oleyl alcohol anti tumor activity through complexation in
      polyvinylalcohol amphiphilic derivatives.
AB  - Oleyl alcohol was complexed with new amphiphilic polyvinylalcohol derivatives
      with the aim of increasing its aqueous solubility, thus improving bioavailability
      and favoring its antitumor activity. Water-soluble amphiphilic polymers were
      prepared by polyvinyl alcohol (PVA) substitution with oleyl chains through a
      succinyl spacer at 2% and 3% substitution degree. The complexes were obtained by
      spray-drying hydroalcoholic solutions of the substituted polymers and free oleyl
      alcohol at different weight ratios (3:1; 5:1; 10:1 w/w). The main physicochemical
      characteristics of the complexes were analyzed and correlated to the cytotoxic
      activity of oleyl alcohol toward tumor cell lines. The complexes strongly
      increased the aqueous solubility of oleyl alcohol and provided oleyl alcohol
      release in the presence of extractive conditions (simulating in vivo absorption).
      The complexes obtained by 10:1 polymer:fatty alcohol weight ratio offered higher
      release rates than the 5:1 and 3:1 ratios, respectively. Complexation also
      increased oleyl alcohol cytotoxicity toward tumor cells due to increased
      availability of the active molecule in the aqueous phase. Pure polymers were
      found to be biocompatible and no toxic effect was detected up to the highest
      concentration used in the present study (500 mu g/ml). The complexation of oleyl
      alcohol with the polymers analyzed here efficiently increased the availability of
      the fatty alcohol in aqueous environment. The enhanced cytotoxicity toward tumor
      cells of the complexed oleyl alcohol and the polymer biocompatibility make these
      amphiphilic PVA derivatives interesting candidates for soluble pharmaceutical
      formulations containing hydrophobic drugs whose therapeutic potential is often
      underestimated due to unsuitable levels of their aqueous solubilization.

PMID- 17497354
TI  - Delivery of prazosin hydrochloride from osmotic pump system prepared by coating
      the core tablet with an indentation.
AB  - The preparation of an osmotic pump tablet was simplified by elimination of laser
      drilling using prazosin hydrochloride as the model drug. The osmotic pump system
      was obtained by coating the indented core tablet compressed by the punch with a
      needle. A multiple regression equation was achieved with the experimental data of
      core tablet formulations, and then the formulation was optimized. The influences
      of the indentation size of the core tablet, environmental media, and agitation
      rate on drug release profile were investigated. The optimal osmotic pump tablet
      was found to deliver prazosin hydrochloride at an approximately constant rate up
      to 24 hr, and independent on both release media and agitation rate. Indentation
      size of core tablet hardly affected drug release in the range of 0.80-1.15 mm.
      The method that is simplified by elimination of laser drilling may be promising
      for preparation of an osmotic pump tablet.

PMID- 17497356
TI  - Stability of vitamins C and E in topical microemulsions for combined antioxidant
      therapy.
AB  - An interesting strategy for protecting skin from excessive exposure to free
      radicals is to support the skin endogenous antioxidant system. As the balance
      between different skin antioxidants is very important, a combined therapy using
      at least two antioxidants is desirable. In the present work, o/w, w/o, and gel
      like microemulsions (ME), all composed of the same ingredients, were selected as
      carrier systems for dermal delivery of vitamins C and E. Gel-like ME was found to
      offer the best protection for both vitamins, although other ME also significantly
      increased their stability compared with that solution. In the presence of vitamin
      C no decrease in vitamin E content occurred. To obtain ME appropriate for dermal
      use, their viscosity was increased by adding thickening agents. On the basis of
      visual examination of viscosity and physical stability of thickened systems,
      several thickeners were selected. The addition of thickener significantly
      increased the viscosity of ME and changed the behavior of systems from ideal
      Newtonian to thixotropic. Finally, the stability of both vitamins was examined as
      a function of thickening agent and of the location of vitamins in the ME. The
      addition of thickeners changed the stability of at least one vitamin, but the
      systems generally still protected vitamins better than solutions. It is likely
      that the changes in internal organization of ME resulting from the addition of
      thickener, confirmed by thermal analysis and changes in solubility of oxygen in
      the outer phase, were the most important factors that influenced the stability of
      vitamins in thickened systems.

PMID- 17497355
TI  - Controlled release of methotrexate from w/o microemulsion and its in vitro
      antitumor activity.
AB  - The objective of this study was to prepare the microemulsion of methotrexate (M
      MTX) for oral use and to investigate the suppressive effect of MTX-loaded
      microemulsion on MCF-7 human breast cancer cells. At the same time this effect of
      M-MTX was compared with those of a solution of the drug (Sol-MTX). Microemulsion
      was composed of soybean oil as oil phase, a mixture of Cremophore EL and Span 80
      as surfactants, and isopropyl alcohol as co-surfactant, and 0.2 N NaOH as the
      aqueous phase. MTX was added into microemulsion at the last stage. We clearly
      demonstrated that M-MTX had a significant cytotoxic effect on breast cancer cell
      lines and the cytotoxic effect of M-MTX was significantly more than that of
      solutions (p < 0.05) and IC(50) value for M-MTX was 40 ng/mL. We also examined M
      MTX and Sol-MTX on a model biological environmental model. For this purpose a
      gastrointestinal cell culture model, the Caco-2 cell line, was used to
      investigate the cytotoxic effects of the polymeric carrier and its effect on the
      cell monolayer integrity. The differences between the viability of cells for M
      MTX and Sol-MTX were significantly different when applied to ANOVA according to 2
      x 8 factorial randomized design (p:0.016; for alpha: 0.05, power : 0.695).
      According to the in vitro cytotoxicity studies, we concluded that when MTX was
      incorporated into the microemulsion (M-MTX), which is a new drug carrier system,
      it suppresses tumour cell growth on multiple tumor lines. These results indicate
      that M-MTX may exert a low cytotoxic effect on normal cells and may be effective
      as an antitumor agent that induces apoptosis.

PMID- 17497357
TI  - Fast-dissolving tablets of glyburide based on ternary solid dispersions with PEG
      6000 and surfactants.
AB  - Marketed glyburide tablets present unsatisfying dissolution profiles that give
      rise to variable bioavailability. With the purpose of developing a fast
      dissolving tablet formulation able to assure a complete drug dissolution, we
      investigated the effect of the addition to a reference tablet formulation of
      different types (anionic and nonionic) and amounts of hydrophilic surfactants, as
      well as the use of a new technique, based on ternary solid dispersions of the
      drug with an hydrophilic carrier (polyethylene glycol [PEG] 6000) and a
      surfactant. Tablets were prepared by direct compression or previous wet
      granulation of suitable formulations containing the drug with each surfactant or
      drug:PEG:surfactant ternary dispersions at different PEG:surfactant w/w ratios.
      The presence of surfactants significantly increased (p<0.01) the drug dissolution
      rate, but complete drug dissolution was never achieved. On the contrary, in all
      cases tablets containing ternary solid dispersions achieved 100% dissolved drug
      within 60 min. The best product was the 10:80:10 w/w ternary dispersion with PEG
      6000 and sodium laurylsulphate, showing a dissolution efficiency 5.5-fold greater
      than the reference tablet formulation and 100% drug dissolution after only 20
      min.

PMID- 17497361
TI  - Mesenchymal stem cells induce endothelial activation via paracine mechanisms.
AB  - Mesenchymal stem cells (MSCs) are bone marrow-derived, pluripotent cells that
      possess the ability to transdifferentiate into various mesenchymal tissues such
      as bone, endothelium, and (heart) muscle. Therefore, these cells may provide a
      therapeutic tool, especially for the treatment of myocardial infarction. The
      interaction of the MSCs with the endothelial barrier and their ability to
      ultimately leave blood vessels after application are crucial in this context. In
      this study, the authors focused on the soluble factors produced by MSCs and their
      effect on the intracellular signal transduction of endothelial cells. The authors
      performed immunohistochemical measurements on human umbilical vein endothelial
      cells (HUVECs) treated with conditioned stem cell medium and took measurements of
      the intracellular nitric oxide (NO) levels and calcium changes. After application
      of conditioned stem cell medium, the authors detected an increase in endothelial
      NO synthase (eNOS) activity by translocation (Ca(2+)) and by phosphorylation
      (increase of pAKT and peNOS1177). Additionally, the authors observed an
      upregulation of pERK within the same time. The phosphorylated eNOS forms are
      linked to these findings and the increase of intracellular NO in the DAF
      measurements. Moreover, conditioned medium also increased intracellular calcium
      levels in endothelial cells. Concluding, the authors postulate that MSCs emit
      soluble factors that alter the NO and calcium levels of endothelial cells and may
      be important for facilitate crossing the endothelial barrier.

PMID- 17497362
TI  - Effects of beta-endorphin on endothelial/monocytic endothelin-1 and nitric oxide
      release mediated by mu1-opioid receptors: a potential link between stress and
      endothelial dysfunction?
AB  - Observations have been made linking the presence of psychosocial factors
      associated with elevated beta-endorphin concentrations with atherosclerosis. In
      this study, the authors assume an important role of the stress hormone beta
      endorphin in several mechanisms that contribute to a dysbalance of human
      endothelial and monocytic endothelin (ET)-1 and nitric oxide (NO) release,
      mediated by mu1-opioid receptors. ET-1 and NO release were quantified via enzyme
      linked immunosorbent assay (ELISA) or fluorometrically. mu1-Opioid receptors were
      identified by polymerase chain reaction (PCR) after stimulation with beta
      endorphin. beta-Endorphin significantly increased endothelial and monocytic ET-1
      release. The effect was mediated by mu1-opioid receptors and abolished by
      naloxonazine, a selective mu1-opioid receptor antagonist. In contrast, NO release
      was decreased under the influence of beta-endorphin. mu1-Opioid receptors on
      human monocytes and endothelial cells mediated a beta-endorphin-induced
      stimulation of ET-1 release, whereas NO release was decreased. Thus, the authors
      hypothesize a role of beta-Endorphin in the pathogenesis of stress-induced
      endothelial dysfunction through peripherally circulating beta-endorphin, which
      may offset the balance of vasoactive mediators, leading to an unopposed
      vasoconstriction. The data may also provide a new concept of mu1-opioid receptor
      antagonists, preventing beta-endorphin-induced disorders of vascular biology.

PMID- 17497363
TI  - Associations between systemic and cerebral endothelial impairment determined by
      cerebrovascular reactivity to L-arginine.
AB  - The relationships between cerebral and systemic endothelial (dys)function and
      between cerebral (dys)function and intima-media thickness (IMT) of carotid
      arteries in patients and healthy volunteers have not yet been clarified. In order
      to explore these issues, the authors performed a post hoc correlation analysis of
      cerebrovascular reactivity to L-arginine, a marker of cerebral endothelial
      function; flow-mediated dilatation (FMD), a marker of systemic endothelial
      function; and IMT of the carotid arteries, a marker of the extent of
      atherosclerosis. Correlations were analyzed in a heterogeneous group consisting
      of 20 patients with lacunar infarctions (LIs) and extensively impaired
      endothelial function, 21 patients with similar risk factors (SRs), but without
      LIs, and 21 healthy controls. Cerebrovascular reactivity to L-arginine was
      determined by the transcranial Doppler method (TCD), FMD by ultrasound
      measurements of the brachial artery after hyperemia, and IMT by measurement of
      the common carotid arteries. Analysis of correlations in the group of 62 subjects
      revealed that L-arginine reactivity, which was diminished in LI and SR patients,
      did not correlate with FMD, which was also diminished in both LI and SR patients
      (Rho = 0.10 with p = 0.458). On the contrary, a significant negative correlation
      was found between L-arginine reactivity and IMT (Rho = -0.30 with p = 0.015). In
      conclusion, our study investigating relations between cerebral and systemic
      endothelial dysfunction showed that cerebral endothelial function, determined by
      L-arginine reactivity, correlates well with the degree of atherosclerosis
      determined by IMT but does not correlate with FMD, suggesting that cerebral and
      systemic endothelial function may not be closely associated.

PMID- 17497364
TI  - Improved identification of endothelial erosion by simultaneous detection of
      endothelial cells (CD31/CD34) and platelets (CD42b).
AB  - Loss of endothelial cells (ECs) with ensuing exposure of thrombogenic
      subendothelial surface is a common cause of thromboembolic complications in
      atherosclerotic arteries. Thus, endothelial denudation has emerged as a major
      contributor to the pathogenesis of atherosclerosis and its complications. Despite
      ongoing efforts in elucidating the pathogenesis of endothelial erosions in human
      atherosclerotic arteries, the mechanisms of erosion have remained enigmatic,
      partly due to lack of well-established methods for its identification. Here the
      authors point out plausible pitfalls in the current methodology and provide an
      improved immunohistochemical method for identifying endothelial erosion; i.e.,
      immunofluorescence double staining with antibodies against CD42b and CD31/CD34.
      This method enables reliable detection of ECs and platelets in the same staining
      by allowing detection of "pseudoendothelium" caused by CD31 staining of a thin
      platelet layer covering sites of endothelial erosion. As erosion with a luminal
      platelet thrombus is likely to represent an in vivo erosion, and erosion without
      platelets an ex vivo artefact, the method makes it possible to exclude
      artefactual erosions resulting from sample processing. The novel immunostaining
      protocol presented here allows more reliable detection of endothelial erosions
      and so may facilitate studies on the mechanisms involved in the pathogenesis of
      plaque erosion and acute coronary syndromes.

PMID- 17497365
TI  - cDNA cloning and some additional peptide characterization of a single-chain
      vascular apoptosis-inducing protein, VAP2.
AB  - Vascular apoptosis-inducing proteins (VAPs) from hemorrhagic snake venom are
      apoptosis-inducing toxins targeting vascular endothelial cells. Well
      characterized VAPs consist of disulfide-bridged double chains (ddVAPs). The
      authors previously described a single-chain VAP (scVAP), VAP2 from Crotalus
      atrox, which also induces apoptosis in endothelial cells (Masuda et al., 1998,
      European Journal of Biochemistry, 253, 36-41). The authors report here the whole
      cDNA sequences and some additional peptide characteristics of VAP2. In addition
      to the apoptosis-inducing activity of VAP2, the toxin displays a cell-detaching
      activity after incubation in high-salt conditions. These observations indicate
      that the apoptosis and cell-detaching functions can be discriminated. Analysis of
      the cell-detaching activity also revealed that VAP2 consists of two similar
      peptides, VAP2A and VAP2B, which are members of the PIII-type snake venom
      metalloproteases (SVMPs). The VAP2A cDNA encodes a 609-amino acid protein. In
      contrast, the peptide sequences of VAP2B were identical to that of
      catrocollastatin, an inhibitor of platelet aggregation. VAP2A and VAP2B interact
      with each other to form a noncovalent dimer similar to the ddVAPs, which was
      detected by native polyacrylamide gel electrophoresis. These data show some new
      characteristics of VAPs, which are important to clarify the apoptotic pathways in
      vascular endothelial cells.

PMID- 17497366
TI  - Blood outgrowth endothelial cells as a vehicle for transgene expression of
      hepatocyte-secreted proteins via Sleeping Beauty.
AB  - The therapeutic use of autologous cells with the capacity for extensive in vitro
      expansion and manipulation prior to host administration has been an area of
      significant investigation over the last decade. Blood outgrowth endothelial cells
      (BOECs) are derived from the circulation and exhibit proliferative growth, in
      vivo engraftment, and survival characteristics for long-term expression of
      endogenously secreted proteins, such as factor VIII (FVIII). The authors describe
      a modified method for the isolation, culture, and expansion of these cells that
      is readily accomplished using standard laboratory methods. Using a commercially
      available transfection reagent, approximately 30% of these primary cells can be
      routinely transfected with the nonviral Sleeping Beauty transposon for long-term,
      stable transgene expression. Moreover, the results indicate that these cells have
      the ability to secrete functionally active proteins that are synthesized
      endogenously by hepatocytes and require post-translational modification including
      alpha1-antitrypsin and clotting factors VII and IX. This, coupled with their
      notably long half-life of years, suggests that these cells may provide an
      appropriate vehicle for secretion of a variety of proteins produced by different
      cell types in vivo. Thus, BOECs have the potential to provide clinically relevant
      secreted proteins for diseases other than those of endothelial origin.

PMID- 17497367
TI  - Nitric oxide generation by NO donors is enhanced following balloon injury in the
      porcine coronary artery.
AB  - Vasospasm is a complication of cardiological procedures such as balloon
      angioplasty and may be related to vascular oxidant stress. Although nitric oxide
      donor drugs are often administered to prevent vasospasm, the response to these
      drugs in balloon-injured arteries has not been studied. Pig coronary arteries
      were balloon-injured in vitro and relaxations to nitric oxide (NO)-donating and
      NO-independent vasodilators studied. Generation of superoxide in response to
      injury was assayed using dihydroethidium. NO formation on addition of the NO
      donor drugs was studied using an amperometric sensor. Expression of
      nitrotyrosine, a peroxynitrite marker, was probed using immunocytochemistry. In
      vitro injury enhanced sensitivity to the NO donors SNAP and SpermineNONOate but
      blunted the response to isoprenaline or chromakalim. With both donors, NO
      formation was significantly enhanced in the presence of an injured vessel.
      Vascular superoxide generation was also increased throughout the vessel wall and
      a small increase in nitrotyrosine was detected in the injured vessel media
      following addition of SNAP. In conclusion, injured vessels were more sensitive to
      NO donors and this appears to be due to enhanced NO generation by the donor
      molecule. Increased formation of peroxynitrite within the injured vessel may
      contribute to the enhanced relaxation in injured vessels.

PMID- 17497368
TI  - Isolation and characterization of human bone-derived endothelial cells.
AB  - Historically, the etiology of local bone pathologies, such as avascular necrosis,
      has been related to intravascular occlusion. Recent reports have highlighted the
      occlusion of arteries, venules, and/or capillaries in bone tissue. Endothelium of
      bone presumably participates locally in the formation of the microvascular
      thrombosis. It is also known that endothelial cells (ECs) play a central role in
      angiogenesis, a process seen in osteosarcoma, amongst other bone diseases. Given
      the well-recognized heterogeneity of ECs throughout the body, investigations of
      local bone disease related to endothelium processes may be more appropriately
      targeted on bone ECs rather than other primary ECs or an immortalized EC line. In
      the current study, mechanical and enzymatic methods are described to isolate ECs
      from cancellous human bone tissue followed by immunomagnetic bead separation to
      purify the cell populations. The human bone-derived endothelial cells (hBDECs)
      were characterized based on endothelial cell antigen expression and functional
      assays. This study is the first report of isolation and expansion of ECs from
      human bone tissue. Isolation of hBDECs in human vascular bone diseases may
      facilitate the study of the molecular and/or genetic abnormalities in the
      vasculature system that contributes to the initiation and/or progression of the
      disease.

PMID- 17497369
TI  - Zoledronate inhibits alphavbeta3 and alphavbeta5 integrin cell surface expression
      in endothelial cells.
AB  - Zoledronate exhibits antiangiogenic properties in vitro and in vivo. Integrins
      alphavbeta3 and alphavbeta5 are involved in angiogenesis. Because zoledronate
      inhibits endothelial cell adhesion, the authors explored the hypothesis that it
      could alter these integrins recruitment to focal adhesion sites. Human umbilical
      vein endothelial cells (HUVECs) were treated with zoledronate or with mevalonate
      pathway intermediates geranylgeraniol (GGOH) and farnesol (FOH). Zoledronate
      generated a significant decrease in alphavbeta3 and alphavbeta5 expression at
      HUVEC cell surface using flow cytometry and immunofluorescence. This inhibition
      was reversed by GGOH but not by FOH. Cells cotreated with zoledronate and GGOH
      were able to attach to vitronectin through alphavbeta3 and alphavbeta5, as
      confirmed by the use of specific function-blocking antibodies. The authors showed
      that zoledronate alters endothelial cell integrin-mediated adhesion. This effect
      is likely to contribute to the previously demonstrated antiangiogenic effect of
      zoledronate. Whether this mechanism of action also applies to metastatic tumor
      cells is under investigation.

PMID- 17497371
TI  - Spontaneous production and use of mnemonic strategies in older adults.
AB  - Mnemonic strategy use in older adults has been measured a number of ways, and
      although strategy measurement has received considerable attention, little work
      has been done to compare various types of subjective strategy reporting. The
      authors compared self-generated and endorsed strategies for memory tasks in a
      sample of 85 African-American and Caucasian older adults and investigated
      demographic characteristics related to each strategy measurement and the
      relationship between strategy use and memory performance. Across memory measures,
      significantly more strategies were endorsed than self-generated. Race, favoring
      Caucasians, was the most salient demographic predictor of mnemonic strategy
      usage. Although strategic behavior was associated with ability performance on
      most memory measures, specific strategies for optimal performance were identified
      for number and story recall only. Findings highlight the importance of measuring
      both self-generated and endorsed strategies and confirm previous work on the
      relationship between strategy use and memory performance.

PMID- 17497370
TI  - Cognitive performance and age: norms from the Maine-Syracuse Study.
AB  - The primary objective of this study was to provide contemporary normative data on
      aging and cognition from an ongoing community-based study. This dementia and
      stroke-free sample (age range = 20-79; mean = 53) consisted of 623 women and 322
      men participating in the Maine-Syracuse Longitudinal Study at waves 4 to 6 (1993
      to 2003). We employed a battery of 22 widely utilized cognitive tests. A 5 (age)
      x 3 (education) x 2 (gender) analysis of variance indicated that, in general,
      higher educated and younger participants exhibited better performance on
      cognitive tests. We found education group to be the strongest, and gender to be
      the weakest, predictor of cognitive performance. However, education cohort was
      not significantly associated with every cognitive outcome, nor was age cohort
      membership. The addition of cardiovascular disease health variables to a model
      including age, education, and gender groupings provided statistically
      significant, but modest, increases in prediction of performance on some tests.
      Results are discussed in relation to findings for previous studies presenting
      normative data on cognitive ability as a function of age, education, and gender.

PMID- 17497372
TI  - Was that part of the story or did i just think so? Age and cognitive status
      differences in inference and story recognition.
AB  - This study expanded the inference and story recognition literature by
      investigating differences within the older age range, differences as a result of
      cognitive impairment, no dementia (CIND), and applying signal detection
      procedures to the analysis of accuracy data. Old-old adults and those with more
      severe CIND showed poorer ability to accurately recognize inferences, and less
      sensitivity in discriminating between statement types. Results support the
      proposal that participants used two different recognition strategies. Old-old and
      CIND adults may be less able to recognize that something plausible with an event
      may not have actually occurred.

PMID- 17497373
TI  - The irrelevant speech effect and the level of interference in aging.
AB  - In general, no disproportionate detrimental effects of irrelevant background
      speech on cognition are found in aging individuals, although this is predicted by
      the inhibitory view of aging. This may be due to the nature of the primary task
      (most studies involve a verbal learning task) or the cognitive level at which
      irrelevant speech interferes with this task. In this study, the irrelevant speech
      effect on a numeric working memory task was investigated among 20 young (M = 21.8
      years) and 20 older (M = 68.1 years) native Dutch individuals. Level of
      interference (LOI) was manipulated by presenting white noise (no interference),
      Russian words (low interference), Dutch words (phonological interference), and
      Dutch numbers (semantic interference) in the background. Results showed that
      reaction time increases as a function of LOI relative to silence, whereas
      accuracy remains unaffected. However, no interaction between LOI and age group
      was found, which suggests that the elderly were not disproportionately affected
      by an increased level of interference. These results are discussed in the light
      of the inhibitory view of aging.

PMID- 17497374
TI  - Effects of age and content of augmented feedback on learning an isometric force
      production task.
AB  - This study addressed the interaction between age and the informational content of
      feedback on learning an isometric force-production task. Healthy men and women
      (30 young adults: 20 to 35 years; 30 older adults: 55 to 70 years) were randomly
      assigned to a certain type of feedback: knowledge of results or kinetic feedback.
      Results showed no differences between young and older adults in the accuracy and
      consistency of performance. There were no interactions of age with any of the
      feedback-related variables. These findings suggest that the effects of augmented
      feedback on motor learning are similar in both young and older adults.

PMID- 17497375
TI  - Lower extremity motor function and disability in mild cognitive impairment.
AB  - Recent findings suggest that lower extremity motor dysfunction may be a feature
      of mild cognitive impairment (MCI), but little is known about the nature and
      significance of lower extremity motor dysfunction in MCI. The aim of this study
      was to examine the extent to which MCI is associated with impaired gait, balance,
      and strength and to examine the relation of lower extremity function to
      disability among persons with MCI in the Rush Memory and Aging Project, a
      clinical-pathologic study of common chronic conditions of old age. In a series of
      analyses adjusted for age, sex, and education, individuals with MCI exhibited
      more impaired gait and balance than individuals without cognitive impairment.
      Because vascular factors can contribute to lower extremity motor dysfunction, the
      authors repeated the initial analyses including terms for vascular risk factors
      and vascular disease, and the associations between MCI and lower extremity motor
      dysfunction persisted. Moreover, among those with MCI, impairments in gait and
      balance were associated with an increased likelihood of disability. These
      findings suggest that lower extremity motor dysfunction is common and contributes
      to disability in MCI, but lower extremity motor dysfunction in MCI does not
      appear to be explained by the vascular factors examined in this study.

PMID- 17497376
TI  - Health reform in the USA: is it time yet?

PMID- 17497377
TI  - Trust influences response to public health messages during a bioterrorist event.
AB  - This study builds on recent work describing African Americans' low trust in
      public health regarding terrorism preparedness by identifying the specific
      components of trust (fiduciary responsibility, honesty, competency, consistency,
      faith) that may influence community response to a bioterrorist attack. We used
      qualitative analysis of data from 75 African American adults living in Los
      Angeles County who participated in focus group discussions. Groups were
      stratified by socioeconomic status (SES; up to vs. above 200% of federal poverty
      guidelines) and age (18-39 years old vs. 40-65 years old). Discussions elicited
      reactions to information presented in escalating stages of a bioterrorism
      scenario. The scenario mimicked the events and public health decisions that might
      occur under such a scenario. Honesty and consistency of information from public
      health officials were the components most frequently identified as determining
      trust or distrust. Patterns of trust varied according to the scenario stage;
      honesty was most important upon initially hearing of a public health crisis,
      whereas fiduciary responsibility and consistency were important upon confirmation
      of a smallpox outbreak and the ensuing public health response. Findings can help
      public health officials design communications that address distrust and enhance
      trust during a bioterrorist event.

PMID- 17497378
TI  - Media depictions of health topics: challenge and stigma formats.
AB  - This article explored the notion that media depictions of health concerns come in
      one of two formats: challenge and stigma. After explicating the five features
      that should appear in challenge format and the seven features of stigma formats,
      we analyzed the content of health messages in magazines, brochures, and posters
      (n = 75) in a metropolitan area. The results of a two-factor confirmatory factor
      model showed that the five suggested features for challenge formats did, indeed,
      appear together (alpha = .76), and the seven features for stigma formats, also,
      appeared together (alpha = .90), and showed no residual relationship. In other
      words, the results suggest that media depictions of health topics appear in
      either challenge or stigma formats (r = - .87). Health issues appearing in
      magazine advertisements and articles presented messages in challenge formats,
      while brochures and posters from largely nonprofit and government groups depicted
      health issues in stigma formats. Some health topics appeared most often in
      challenge formats (including cancer, heart disease, and scoliosis), while others
      appeared in stigma formats (including tuberculosis, hepatitis, smoking, and
      sexually transmitted diseases [STDs]). Findings suggest that media depictions of
      health differ, and the implications of stigma and challenge formats are
      discussed.

PMID- 17497379
TI  - Protecting children from myopia: a PMT perspective for improving health marketing
      communications.
AB  - This research examined the predictive utility of the protection motivation theory
      (PMT) model for myopia prevention amongst children. An integrative model for
      myopia prevention behavior of parents was first developed in the context of
      theory and survey instruments then refined using information gathered from two
      focus groups. Empirical data then was collected from parents of primary school
      children in Singapore, a country with one of the highest rates of myopia in the
      world, and analyzed using structural equation modeling (SEM). Our findings
      revealed that coping appraisal variables were more significantly associated with
      protection motivation, relative to threat appraisal variables. In particular,
      perceived self-efficacy was the strongest predictor of parental intention to
      enforce good visual health behaviors, while perceived severity was relatively
      weak. Health marketing communications and public policy implications are
      discussed.

PMID- 17497380
TI  - Local media monitoring in process evaluation. Experiences from the Stockholm
      Diabetes Prevention Programme.
AB  - We present a rationale and approach for longitudinal analyses of media coverage
      and content, and illustrate how media monitoring can be used in process
      evaluations. Within a community-based diabetes prevention project, the Stockholm
      Diabetes Prevention Program, we analyzed the frequency, prominence, and framing
      of physical activity in local newspapers of three intervention and two control
      municipalities. In total, 2,128 stories and advertisements related to physical
      activity were identified between the years 1997 and 2002. Although stories about
      physical activity were relatively few (n = 224), they were prominently located in
      all five local newspapers. Physical activity was framed rather similarly in the
      municipalities. Health aspects, however, were expressed to a greater extent in
      stories in two of the intervention municipalities. A limited portion (14%) of the
      articles could be linked directly to the program. It is not possible to assess to
      what extent the program has had a disseminating effect on the newspapers' health
      related content in general, due to weaknesses of the process tracking system and
      limitations of the study design. Implications for the design is that an
      evaluative framework should be preplanned and include data collection about media
      relationships, media's interest in public health, media coverage prior to the
      program and coverage in other media for comparisons of general trends in the
      reporting. The material and the current database, however, provide a good basis
      for quantitative content analysis and qualitative discourse analysis to yield
      information on the type, frequency, and content of health reporting in local
      newspapers.

PMID- 17497385
TI  - Theoretical and experimental investigations on the size of alginate microspheres
      prepared by dropping and spraying.
AB  - In order to produce functional microspheres with different ranges of sizes for
      various applications, the size of alginate droplets prepared by dropping and
      spraying was studied. It was shown that the mean diameter could be controlled by
      liquid flow velocity and applied voltage as operating parameters using a
      conventional dropping and an electrostatic dropping method, separately. The
      formation mechanism of alginate droplets could be categorized into two different
      modes: Dripping mode and jetting mode. By employing an effective force analysis,
      the diameters in each modes showed to be well agreed with the numerical
      simulation within 7% deviations. It was testified that the initial amount of
      surface charges had a high impact on droplet diameter and the liquid flow
      velocity played a more important role on mean diameter of alginate droplets by
      electrostatic dropping method in dripping mode than in jetting mode. Then, an
      empirical equation and a semi-empirical model were used to simulate the diameter
      of droplets obtained by spraying and spraying with electrostatic field (SEF)
      method, respectively. The decrease in diameter was more sensitive to the increase
      of gas flow rate than to the decrease of liquid flow rate, and the results of two
      models fitted well with experimental values. The simulations showed that SEF
      yielded a 20% lower on droplet diameter than simple spraying method.

PMID- 17497381
TI  - Understanding health inequalities for uninsured Americans: a population-wide
      survey.
AB  - Numbers of the uninsured in America have risen in the past few years to more than
      40 million people, yet relatively little is known about their health
      communication behaviors. Data from the 2003 Health Information National Trends
      Survey (HINTS) were used to analyze the relationship among demographics, health
      status, health insurance status, online health seeking, and amount of attention
      paid to various media for health. A random sample of 6,369 Americans indicated
      several statistically significant differences between the insured and uninsured:
      the uninsured were more likely younger, less educated, and Hispanic. Findings
      also indicated that those without health insurance reported being less healthy
      and more distressed and hold a greater risk perception for cancer, compared with
      their insured counterparts. Health insurance, when controlling for demographics
      and health status, explained a statistically significant but small amount of
      variance in both online health seeking and attention to health messages in
      various other media.

PMID- 17497386
TI  - Polyvinylamine-based capsules: a mechanistic study of the formation using
      alginate and cellulose sulphate.
AB  - Capsules based on sodium alginate (SA) and sodium cellulose sulphate (SCS), have
      been prepared using polyvinylamines (PVAm) of varying intrinsic viscosities. The
      resulting capsules are relatively dense in nature, revealing a bursting force
      which is four times that observed for the classical SA/SCS/polymethylene-co
      guanidine chemistry. Molar mass cutoffs were typically in the 10-70 kDa range. A
      mechanistic study was carried out where the reaction time, ionic strength and pH
      of the reaction mixture, as well as the stoichiometry of the polyanion blend and
      the PVAm molar mass were varied. It is postulated that both the SA-PVAm and the
      SCS-PVAm binary interactions contribute to the mechanical properties and the
      permeability of the resulting capsules. The polyvinylamine-based chemistry offers
      interesting alternatives to the PMCG system in that it provides a means to
      produce capsules at low, or zero, ionic strengths. Subtle changes in the pH, or
      the SA:SCS ratio, can also be used to tune the bursting force quite sensitively.
      The most appropriate capsules, for transplantation, would likely be formed at
      polyanion levels of 1.2 wt% with a PVAm molar mass below 17 kDa.

PMID- 17497387
TI  - Pro-inflammatory cytokine inhibition in the primate using microencapsulated
      antisense oligomers to NF-kappaB.
AB  - PRIMARY OBJECTIVE: Antisense oligomers to NF-kappaB (ASO) were incorporated into
      albumin microspheres to determine if microcapsules containing ASO inhibit pro
      inflammatory cytokines to a greater extent than comparable doses of ASO in
      solution. Phagocytosis of microcapsules and intracellular release of ASO in
      macrophages was evaluated. RESEARCH DESIGN: Comparable doses of microencapsulated
      ASO and ASO in solution were evaluated in non-human primates. METHODS: Blood was
      sampled and stimulated with Escherichia coli endotoxin ex vivo. TNF, IL-1 and IL
      6 concentrations were compared for 72 hrs. The intracellular concentration of ASO
      was measured in macrophages in vitro to evaluate the difference in intracellular
      penetration of microencapsulated ASO. RESULTS: Microencapsulated ASO produced
      significantly greater cytokine inhibition at all time points compared to ASO in
      solution. There were no side effects to ASO in the baboons. Intracellular ASO
      concentration was 10 fold greater in macrophages using microencapsulation.
      CONCLUSIONS: Microencapsulated ASO to NF-kappaB is more effective than ASO in
      solution in pro-inflammatory cytokine inhibition in non-human primates.

PMID- 17497388
TI  - Investigation of alternative compounds to poly(E-MA) as a polymeric surfactant
      for preparation of microcapsules by phase separation method.
AB  - Various water-soluble polymers were used to examine an alternative emulsifier for
      poly(ethylene-alt-maleic anhydride), used in the preparation of crosslinked
      polyurea microcapsules. Microcapsules were successfully prepared by using the
      water-soluble polymers with large molecular weight alternating copolymers, namely
      poly(olefin-maleic anhydride), poly(olefin-maleic acid), and poly(acrylic acid).
      On the other hand, no microcapsule resulted from olefin-maleic acid with small
      molecular weight alternating copolymers. From these results, the following
      guidelines were obtained for the selection of polymeric surfactants suitable for
      crosslinked polyurea microcapsule. A polymeric surfactant must have maleic acid
      or a carboxyl group in order to form a crosslinked polyurea microcapsule
      membrane. Furthermore, to form a stronger capsule membrane it is desirable to
      have a maleic anhydride group. It is also important for membrane formation that
      the polymeric surfactant has a suitable molecular weight.

PMID- 17497389
TI  - Formulation of maltodextrin entrapped in polycaprolactone microparticles for
      protein and vaccine delivery: effect of size determining formulation process
      variables of microparticles on the hydrodynamic diameter of BSA.
AB  - Size of the microparticle and integrity of the released protein are two crucial
      factors which dictate the success of any protein or vaccine delivery system. The
      primary objective was to optimize bovine serum albumin (BSA) loaded
      polycaprolactone/maltodextrin (PCL/MD) microparticles in terms of its size and
      the hydrodynamic diameter of the released protein. The effect of size determining
      formulation process variables (SDFPV) of microparticles on the hydrodynamic
      diameter of protein antigen was determined. The SDFPV were optimized by a
      compromise between the microparticle size and the relative hydrodynamic stability
      of protein released from it. Percentage of secondary structure of the protein
      released from the optimized formulation as determined by circular dichroism
      spectra along with SELCON software was also similar to that of native BSA
      suggesting the potential of PCL /MD microparticles for protein or vaccine
      delivery.

PMID- 17497395
TI  - Clarification to "pilot measurements of ELF contact currents in some electric
      utility operations".

PMID- 17497390
TI  - Sulindac loaded alginate beads for a mucoprotective and controlled drug release.
AB  - Ionotropic gelation was used to entrap sulindac into calcium alginate beads as a
      potential drug carrier for the oral delivery of this anti-inflammatory drug.
      Beads were investigated in vitro for a possible sustained drug release and their
      use in vivo as a gastroprotective system for sulindac. Process parameters such as
      the polymer concentration, polymer/drug ratio, and different needle diameter were
      analysed for their influences on the bead properties. Size augmented with
      increasing needle diameter (0.9 mm needle: 1.28 to 1.44 mm; 0.45 mm needle: 1.04
      to 1.07 mm) due to changes in droplet size as well as droplet viscosity. Yields
      varied between 87% and 98% while sulindac encapsulation efficiencies of about 88%
      and 94% were slightly increasing with higher alginate concentrations. Drug
      release profiles exhibited a complete release for all formulations within 4 hours
      with a faster release for smaller beads. Sulindac loaded alginate beads led to a
      significant reduction of macroscopic histological damage in the stomach and
      duodenum in mice. Similarly, microscopic analyses of the mucosal damage
      demonstrated a significant mucoprotective effect of all bead formulation compared
      to the free drug. The present alginate formulations exhibit promising properties
      of a controlled release form for sulindac; meanwhile they provide a distinct
      tissue protection in the stomach and duodenum.

PMID- 17497396
TI  - "The fouled player should not take the penalty himself": an empirical
      investigation of an old German football myth.
AB  - In this study, we investigate the old German football myth that the fouled player
      should not take the resulting penalty himself, as he is at an increased risk of
      missing. Previous analyses are improved on as we adjust for potential confounders
      that might influence self-taking as well as successful penalty conversion. Our
      findings reveal some important predictors for self-taking but, somewhat
      surprisingly, neither self-taking nor any of the potential confounders predicts
      scoring a penalty kick.

PMID- 17497397
TI  - Determinants of possession of the ball in soccer.
AB  - In research on the importance of the possession of the ball in soccer, little
      attention has been paid to its determinants. Using data from 170 matches of the
      2003 - 2004 Spanish Soccer League, we explain why differences in the possession
      of the ball among teams are so great. In particular, four variables are examined:
      evolving match status (i.e. whether the team is winning, losing or drawing),
      venue (i.e. playing at home or away), and the identities of the team and the
      opponent in each match. Results of linear regression analysis show that these
      four variables are statistically significant and together explain most of the
      variance in possession. In short, home teams have more possession than away
      teams, teams have more possession when they are losing matches than when winning
      or drawing, and the identity of the opponent matters - the worse the opponent,
      the greater the possession of the ball. Combinations of these variables could be
      used to develop a model that predicts possession in soccer.

PMID- 17497398
TI  - The influence of drink temperature on thermoregulatory responses during prolonged
      exercise in a moderate environment.
AB  - Nine males cycled at 53% (s = 2) of their peak oxygen uptake (VO(2peak)) for 90
      min (dry bulb temperature: 25.4 degrees C, s = 0.2; relative humidity: 61%, s =
      3). One litre of flavoured water at 10 (cold), 37 (warm) or 50 degrees C (hot)
      was ingested 30 - 40 min into exercise. Immediately after the 90 min of exercise,
      participants cycled at 95%VO(2peak) to exhaustion to assess exercise capacity.
      Rectal and mean skin temperatures and heart rate were recorded. The gradient of
      rise in rectal temperature was influenced (P < 0.01) by drink temperature. Mean
      skin temperature was highest in the hot trial (cold trial: 34.2 degrees C, s =
      0.5; warm trial: 34.4 degrees C, s = 0.5; hot trial: 34.7 degrees C, s = 0.6; P <
      0.01). Significant differences were observed in heart rate (cold trial: 132 beats
      . min(-1), s = 13; warm trial: 134 beats . min(-1), s = 12; hot trial: 139 beats
      . min(-1), s = 13; P < 0.05). Exercise capacity was similar between trials (cold
      trial: 234 s, s = 69; warm trial: 214 s, s = 52; hot trial: 203 s, s = 53; P =
      0.562). The heat load and debt induced via drinking resulted in appropriate
      thermoregulatory reflexes during exercise leading to an observed heat content
      difference of only 33 kJ instead of the predicted 167 kJ between the cold and hot
      trials. These results suggest that there may be a role for drink temperature in
      influencing thermoregulation during exercise.

PMID- 17497399
TI  - Helsen, Gilis and Weston (2006) err in testing the optical error hypothesis.
AB  - In this commentary, we react to the recent study by Helsen, Gilis and Weston
      (2006) on judging offside in football. Helsen et al. claim that their data
      falsify the optical error hypothesis presented by Oudejans et al. (2000).
      However, as we will elucidate here, they misinterpret this hypothesis and present
      a data set that is seriously flawed, and hence not suited to test it. Therefore,
      their conclusions regarding the optical error hypothesis are in error.

PMID- 17497400
TI  - Helsen, Gilis, and Weston (2006) do not err in questioning the optical error
      hypothesis as the only major account for explaining offside decision-making
      errors.
AB  - Oudejans, Bakker, and Beek (2007) recognize several relevant aspects of offside
      judgements in association football in the paper by Helsen, Gilis, and Weston
      (2006). We agree that the existing knowledge base on offside assessment needs to
      be expanded for two reasons. First, from a theoretical point of view it is
      important to examine how assistant referees can learn to deal with the
      limitations of the human visual information processing system. Second, from a
      practical point of view it is relevant to understand better refereeing
      performances and to identify potential explanations for incorrect offside
      decisions that could impact on the final outcome of the game. Oudejans et al.
      (2007) believe we both misinterpreted the optical error hypothesis and that our
      data set was unsuited to test it. Below, we react to these comments.

PMID- 17497401
TI  - Cardiopulmonary loading in motocross riding.
AB  - The present study was designed to examine physiological responses during
      motocross riding. Nine Finnish A-level motocross riders performed a 15-min ride
      at a motocross track and a test of maximal oxygen uptake (VO2max) in the
      laboratory. Cardiopulmonary strain was measured continuously during the ride as
      well as in the VO2max test. During the ride, mean VO2 was 32 ml x kg(-1) x min(
      1) (s = 4), which was 71% (s = 12) of maximum, while ventilation (V(E)) was 73%
      (s = 15) of its maximum. The relative VO2 and V(E) values during the riding
      correlated with successful riding performance (r = 0.80, P < 0.01 and r = 0.79, P
      < 0.01, respectively). Mean heart rate was maintained at 95% (s = 7) of its
      maximum. Mean blood lactate concentration was 5.0 mmol x l(-1) (s = 2.0) after
      the ride. A reduction of 16% (P < 0.001) in maximal isometric handgrip force was
      observed. In conclusion, motocross causes riders great physical stress. Both
      aerobic and anaerobic metabolism is required for the isometric and dynamic muscle
      actions experienced during a ride.

PMID- 17497402
TI  - Variable versus constant power strategies during cycling time-trials: prediction
      of time savings using an up-to-date mathematical model.
AB  - Swain (1997) employed the mathematical model of Di Prampero et al. (1979) to
      predict that, for cycling time-trials, the optimal pacing strategy is to vary
      power in parallel with the changes experienced in gradient and wind speed. We
      used a more up-to-date mathematical model with validated coefficients (Martin et
      al., 1998) to quantify the time savings that would result from such optimization
      of pacing strategy. A hypothetical cyclist (mass = 70 kg) and bicycle (mass = 10
      kg) were studied under varying hypothetical wind velocities (-10 to 10 m x s(
      1)), gradients (-10 to 10%), and pacing strategies. Mean rider power outputs of
      164, 289, and 394 W were chosen to mirror baseline performances studied
      previously. The three race scenarios were: (i) a 10-km time-trial with
      alternating 1-km sections of 10% and -10% gradient; (ii) a 40-km time-trial with
      alternating 5-km sections of 4.4 and -4.4 m x s(-1) wind (Swain, 1997); and (iii)
      the 40-km time-trial delimited by Jeukendrup and Martin (2001). Varying a mean
      power of 289 W by +/- 10% during Swain's (1997) hilly and windy courses resulted
      in time savings of 126 and 51 s, respectively. Time savings for most race
      scenarios were greater than those suggested by Swain (1997). For a mean power of
      289 W over the "standard" 40-km time-trial, a time saving of 26 s was observed
      with a power variability of 10%. The largest time savings were found for the
      hypothetical riders with the lowest mean power output who could vary power to the
      greatest extent. Our findings confirm that time savings are possible in cycling
      time-trials if the rider varies power in parallel with hill gradient and wind
      direction. With a more recent mathematical model, we found slightly greater time
      savings than those reported by Swain (1997). These time savings compared
      favourably with the predicted benefits of interventions such as altitude training
      or ingestion of carbohydrate-electrolyte drinks. Nevertheless, the extent to
      which such power output variations can be tolerated by a cyclist during a time
      trial is still unclear.

PMID- 17497403
TI  - Methodological issues associated with longitudinal research: findings from the
      Leuven Longitudinal Study on Lifestyle, Fitness and Health (1969 - 2004).
AB  - Longitudinal studies provide unique opportunities but are also faced with several
      limitations. The purpose of this study was to document three of these issues
      ("imperfect" design, evolution of data collection methods, representativeness) by
      means of the Leuven Longitudinal Study on Lifestyle, Fitness and Health (LLSLFH).
      The LLSLFH (1969 - 2004) comprises observations on males between 12 and 18 years
      and at 30, 35, 40, and 47 years, and on females at 16 and 40 years. In the most
      recent phase of the study, spouses and offspring were also included. The
      different phases and evolving research questions throughout the LLSLFH required
      an appropriate adaptation of the research design. The associated evolution of
      data collection methods largely reflects the changing ideas about physical
      fitness, body composition, and physical activity, the continuing search for new
      and better measurement techniques, and the need for adaptations with age. Ongoing
      study participants are representative in terms of body composition and, except
      for adolescence in males, also physical activity. No straightforward answer can
      be given concerning physical fitness. In both sexes, socio-economic status is
      above average. When informed about the possible "pitfalls" of longitudinal
      research in advance, several measures could be taken to prevent or limit them as
      much as possible.

PMID- 17497404
TI  - A mathematical model of the oar blade - water interaction in rowing.
AB  - Our aim was to present a mathematical model of rowing and sculling that allowed
      for a comparison of oar blade designs. The relative movement between the oar
      blades and water during the drive phase of the stroke was modelled, and the lift
      and drag forces generated by this complex interaction were determined. The model
      was driven by the oar shaft angular velocity about the oarlock in the horizontal
      plane, and was shown to be valid against measured on-water mean steady-state
      shell velocity for both a heavyweight men's eight and a lightweight men's single
      scull. Measured lift and drag force coefficients previously presented by the
      authors were used as inputs to the model, whichs allowed for the influence of oar
      blade design on rowing performance to be determined. The commonly used Big Blade,
      which is curved, and it's flat equivalent were compared, and blade curvature was
      shown to generate a 1.14% improvement in mean boat velocity, or a 17.1-m lead
      over 1500 m. With races being won and lost by much smaller margins than this,
      blade curvature would appear to play a significant role in propulsion.

PMID- 17497405
TI  - Muscle - tendon unit mechanical and morphological properties and sprint
      performance.
AB  - The objective of this study was to determine whether sprint performance is
      related to the mechanical (elongation - force relationship of the tendon and
      aponeurosis, muscle strength) and morphological (fascicle length, pennation
      angle, muscle thickness) properties of the quadriceps femoris and triceps surae
      muscle - tendon units. Two groups of sprinters (slow, n = 11; fast, n = 17)
      performed maximal isometric knee extension and plantar flexion contractions on a
      dynamometer at 11 different muscle - tendon unit lengths. Elongation of the
      tendon and aponeurosis of the gastrocnemius medialis and the vastus lateralis was
      measured using ultrasonography. We observed no significant differences in maximal
      joint moments at the ankle and knee joints or morphological properties of the
      gastrocnemius medialis and vastus lateralis between groups (P > 0.05). The fast
      group exhibited greater elongation of the vastus lateralis tendon and aponeurosis
      at a given tendon force, and greater maximal elongation of the vastus lateralis
      tendon and aponeurosis during maximum voluntary contraction (P < 0.05).
      Furthermore, maximal elongation of the vastus lateralis tendon and aponeurosis
      showed a significant correlation with 100-m sprint times (r = -0.567, P = 0.003).
      For the elongation - force relationship at the gastrocnemius medialis tendon and
      aponeurosis, the two groups recorded similar values. It is suggested that the
      greater elongation of the vastus lateralis tendon and aponeurosis of the fast
      group benefits energy storage and return as well as the shortening velocity of
      the muscle - tendon unit.

PMID- 17497406
TI  - The moral worth of sport reconsidered: contributions of recreational sport and
      competitive sport to life aspirations and psychological well-being.
AB  - Based on self-determination theory, the present study aimed to test the
      hypothesis that importance ratings of life aspirations would mediate the effects
      of participation in recreational and competitive sport on psychological well
      being. In addition, the effects of sport participation on psychological well
      being were hypothesized to indicate that, compared with competitive athletes,
      recreational athletes would report higher psychological well-being. The
      participants were 118 university students (83 males, 35 females) with a mean age
      of 20.8 years (s = 7.6). In accordance with the initial hypotheses, a path
      analysis supported the mediating effect of importance ratings of life
      aspirations, but not of attainment ratings of life aspirations, on the
      relationship between participation in recreational and competitive sport and
      psychological well-being. The indirect effects observed for importance ratings
      supported the conclusion that recreational athletes showed a preference for
      intrinsic life aspirations compared with competitive athletes and reported higher
      psychological well-being. Overall, the findings of the present study suggest that
      the moral worth of sport does not reside so much in the frequency with which
      individuals engage in sport but in the goals and values people express through
      sport participation.

PMID- 17497407
TI  - The effects of perceived and received support on self-confidence.
AB  - A sample of 222 university athletes (mean age 19.8 years, s = 2.0), ranging in
      standard from university second team to international competitor, completed a
      measure of perceived support 2 weeks before an important competition or match. On
      the day before the competition or match, the athletes completed measures of
      stressors, stress, received support, and self-confidence. Moderated hierarchical
      regression analyses revealed the following key findings: (i) main effects for
      both perceived (DeltaR2 = 0.11) and received support (DeltaR2 = 0.14) upon self
      confidence; (ii) stress-buffering effects for both perceived (DeltaR2 = 0.02) and
      received (DeltaR2 = 0.07) support upon self-confidence; (iii) when both aspects
      of support were considered simultaneously, stress-buffering effects were
      primarily attributable to the influence of received support. These results
      demonstrate the beneficial impact of social support on self-confidence, both
      directly and by reducing the negative effect of stress on self-confidence. Our
      findings emphasize the need to recognize the distinction between perceived and
      received support, both in terms of theory and the design of social support
      interventions with athletes.

PMID- 17497409
TI  - In vitro dermal absorption of methyl salicylate, ethyl parathion, and malathion:
      first responder safety.
AB  - In vitro tests with fresh dermatomed (0.3 to 0.4 mm thick) female breast skin and
      one leg skin specimen were conducted in Bronaugh flow-through Teflon diffusion
      cells with three chemicals used to simulate chemical warfare agents: 14C
      radiolabeled methyl salicylate (MES), ethyl parathion (PT), and malathion (MT),
      at three dose levels (2, 20, and 200 mM). Tests were conducted at a skin
      temperature of 29 degrees C using a brief 30-min exposure to the chemical and a
      6.5-h receivor collection period. Rapid absorption of all three chemicals was
      observed, with MES absorbed about 10-fold faster than PT and MT. For MES, PT, and
      MT, respectively, there was 32%, 7%, and 12% absorption into the receivor
      solution (Hank's HEPES buffered saline with 4% bovine serum albumin [BSA], pH
      7.4) at the low dose (2 mM), 17%, 2%, and 3% at the medium dose (20 mM), and 11%,
      1%, and 1% at the high dose (200 mM) levels. Including the skin depot for MES,
      PT, and MT, respectively, there was 40%, 41%, and 21% (low dose), 26%, 16%, and
      8% (medium dose), and 13%, 19%, and 10% (high does) absorption. Efficacy of skin
      soap washing conducted at the 30 min exposure time ranged from 31% to 86%,
      varying by chemical and dose level. Skin depot levels were highest for the
      relatively lipophilic PT. "Pseudo" skin permeability coefficient (K(p)) data
      declined with dose level, suggesting skin saturation had occurred. An in-depth
      comparison with literature data was conducted and risk assessment of first
      responder exposure was briefly considered.

PMID- 17497410
TI  - Nitrate in drinking water and risk of death from bladder cancer: an ecological
      case-control study in Taiwan.
AB  - The relationship between nitrate levels in drinking water and bladder cancer
      development is controversial. A matched cancer case-control with nitrate ecology
      study was used to investigate the association between bladder cancer mortality
      occurrence and nitrate exposure from Taiwan drinking water. All bladder cancer
      deaths of Taiwan residents from 1999 through 2003 were obtained from the Bureau
      of Vital Statistics of the Taiwan Provincial Department of Health. Controls were
      deaths from other causes and were pair-matched to the cases by gender, year of
      birth,and year of death. Each matched control was selected randomly from the set
      of possible controls for each cancer case. Data on nitrate-nitrogen (NO3-N)
      levels in drinking water throughout Taiwan were collected from Taiwan Water
      Supply Corporation (TWSC). The municipality of residence for cancer cases and
      controls was assumed to be the source of the subject's nitrate exposure via
      drinking water. The adjusted odds ratios for bladder cancer death for those with
      high nitrate levels in their drinking water were 1.76 (1.28-2.42) and 1.96 (1.41
      2.72) as compared to the lowest tertile. The results of the present study show
      that there was a significant positive relationship between the levels of nitrate
      in drinking water and risk of death from bladder cancer.

PMID- 17497411
TI  - Early embryonic exposure to polychlorinated biphenyls disrupts heat-shock protein
      70 cognate expression in zebrafish.
AB  - Polychlorinated biphenyls (PCBs) are persistent environmental contaminants that
      have documented neurological effects in children exposed in utero. To better
      define neuronally linked molecular targets during early development, zebrafish
      embryos were exposed to Aroclor 1254, a mixture of PCB congeners that are common
      environmental contaminants. Microarray analysis of the zebrafish genome revealed
      consistent significant changes in 38 genes. Of these genes, 55% (21) are
      neuronally related. One gene that showed a consistent 50% reduction in expression
      in PCB-treated embryos was heat-shock protein 70 cognate (Hsc70). The reduction
      in Hsc70 expression was confirmed by real-time polymerase chain reaction (PCR),
      revealing a consistent 30% reduction in expression in PCB-treated embryos. Early
      embryonic exposure to PCBs also induced structural changes in the ventro-rostral
      cluster as detected by immunocytochemistry. In addition, there was a significant
      reduction in dorso-rostral neurite outgrowth emanating from the RoL1 cell cluster
      following PCB exposure. The serotonergic neurons in the developing diencephalon
      showed a 34% reduction in fluorescence when labeled with a serotonin antibody
      following PCB exposure, corresponding to a reduction in serotonin concentration
      in the neurons. The total size of the labeled neurons was not significantly
      different between treated and control embryos, indicating that the development of
      the neurons was not affected, only the production of serotonin within the
      neurons. The structural and biochemical changes in the developing central nervous
      system following early embryonic exposure to Aroclor 1254 may lead to alterations
      in the function of the affected regions.

PMID- 17497412
TI  - Quantification of the neurotoxic beta-carboline harmane in barbecued/grilled meat
      samples and correlation with level of doneness.
AB  - Harmane, one of the heterocyclic amines (HCAs), is a potent neurotoxin linked to
      human diseases. Dietary exposure, especially in cooked meats, is the major source
      of exogenous exposure for humans. However, knowledge of harmane concentrations in
      cooked meat samples is limited. Our goals were to (1) quantify the concentration
      of harmane in different types of cooked meat samples, (2) compare its
      concentration to that of other more well-understood HCAs, and (3) examine the
      relationship between harmane concentration and level of doneness. Thirty
      barbecued/grilled meat samples (8 beef steak, 12 hamburger, 10 chicken) were
      analyzed for harmane and four other HCAs (2-amino-1-methyl-6-phenylimidazo [4,5
      b]pyridine [PhIP], amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], 2-amino
      3,4,8-trimethylimidazo[4,5-f]quinoxaline [DiMeIQx], and 2-amino-1,6
      dimethylfuro[3,2-e]imidazo[4,5-b]pyridine [IFP]). Mean (+/- SD) harmane
      concentration was 5.63 (+/- 6.63) ng/g; harmane concentration was highest in
      chicken (8.48 +/- 9.86 ng/g) and lowest in beef steak (3.80 +/- 3.6 ng/g).
      Harmane concentration was higher than that of the other HCAs and significantly
      correlated with PhIP concentration. Harmane concentration was associated with
      meat doneness in samples of cooked beef steak and hamburger, although the
      correlation between meat doneness and concentration was greater for PhIP than for
      harmane. Evidence indicates that harmane was detectable in nanograms per gram
      quantities in cooked meat (especially chicken) and, moreover, was more abundant
      than other HCAs. There was some correlation between meat doneness and harmane
      concentration, although this correlation was less robust than that observed for
      PhIP. Data such as these may be used to improve estimation of human dietary
      exposure to this neurotoxin.

PMID- 17497413
TI  - Increased neurotrophin production in a Penicillium chrysogenum-induced allergic
      asthma model in mice.
AB  - Neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic
      factor (BDNF), and neurotrophin (NT)-3, have been implicated in the pathogenesis
      of many features and symptoms of asthma. The role of neurotrophins in fungal
      allergic asthma, however, is unknown. Repeated pulmonary challenge with
      Penicillium chrysogenum extract (PCE) induces dose-dependent allergic asthma-like
      responses in mice. The aim of this study was to investigate whether neurotrophins
      are involved in the PCE-induced allergic airway response in mice. Mice were
      exposed to 10, 20, 50, or 70 microg PCE by involuntary aspiration 4 times over 1
      mo. Bronchial alveolar lavage fluid (BALF) was collected immediately before and
      after the final exposure. The levels of NGF, NT-3, and NT-4 were determined by
      enzyme-linked immunosorbent assay (ELISA). The lungs were fixed and processed for
      immunohistochemical examination of NGF production. PCE-exposed mice had dose
      dependent increases in NGF, NT-3, and NT-4 in both BALF and sera. Exposures to
      PCE produced elevation in positive immunohistochemical staining for NGF in the
      airway epithelium and smooth muscle cells, in addition to infiltrated cells such
      as mononuclear cells, eosinophils, and macrophages. Taken together, this is the
      first study to link fungal allergic asthma in an experimental model with enhanced
      production of neurotrophins in the airways, and suggests that neurotrophins may
      play a role in the etiology of mold-induced asthma in humans.

PMID- 17497414
TI  - Postnatal growth considerations for PBPK modeling.
AB  - A physiologically based pharmacokinetic (PBPK) model and Windows-based program
      (called PostNatal) was developed that focuses on postnatal growth, from birth
      through adulthood, using appropriate growth curves for each species and gender.
      Postnatal growth algorithms relating organs/tissues weights with total body
      weight for male and female humans, dogs, rats, and mice are an integral part of
      the software and are utilized to assign the appropriate weight and blood flow for
      each of 22 organs/tissues for each simulation. Upper limits of body weight were
      chosen that reflect the available data used to define the algorithms; above these
      limits a set percent body weight was assigned to all organs/tissues.

PMID- 17497415
TI  - Evaluation of the effects of subchronic oral administration of n-butyl maleate in
      Sprague-Dawley rats.
AB  - n-Butyl maleate, also referred to as monobutyl maleate, is an ester of maleic
      acid, which is used as a counterion in the pharmaceutical industry. While
      substantial published data exist on short-term treatment, maleic acid-induced
      renal toxicity in the rat, no toxicity data are available on the monobutyl ester.
      This study evaluated the oral subchronic nephrotoxicity potential of n-butyl
      maleate administered to Sprague-Dawley rats (10/males and females/group) at doses
      of 0 (vehicle control), 10, 30, or 60 mg/kg/d for 2 wk. Statistically significant
      elevations in organ weights were noted in males at 60 mg/kg/d and included: (a)
      increases in absolute heart, kidney, and liver weights; (b) increased liver to
      body weight ratios; and (c) increased heart, kidney, liver, spleen, and
      epididymides to brain weight ratios. In females, statistically significant
      increases in organ weights were limited to increases in adrenal to brain weights
      at > or = 10 mg/kg/d, kidney to brain weights at > or = 30 mg/kg/d, and kidney to
      body weight and liver to brain weight ratios at 60 mg/kg/d. There were no
      macroscopic or microscopic pathology changes observed in any of the tissues
      examined. Importantly, light microscopic examination of the kidney was
      unremarkable at the end of the 2-wk dosing period with n-butyl maleate. Although
      lacking a histopathological correlate, resultant increases in organ weights at 60
      mg/kg/d might be considered indicative of an adverse effect. However, renal
      perturbation induced by n-butyl maleate was mild in comparison to maleic acid
      induced renal toxicity, which manifested as impaired tubular resorption and
      necrosis of the proximal tubules at doses > or = 60 mg/kg/d. The no-observed
      adverse-effect level (NOAEL) for the study was 30 mg/kg/d.

PMID- 17497416
TI  - Mercury, lead, and zinc in baby teeth of children with autism versus controls.
AB  - This study determined the level of mercury, lead, and zinc in baby teeth of
      children with autism spectrum disorder (n = 15, age 6.1 +/- 2.2 yr) and typically
      developing children (n = 11, age = 7 +/- 1.7 yr). Children with autism had
      significantly (2.1-fold) higher levels of mercury but similar levels of lead and
      similar levels of zinc. Children with autism also had significantly higher usage
      of oral antibiotics during their first 12 mo of life, and possibly higher usage
      of oral antibiotics during their first 36 mo of life. Baby teeth are a good
      measure of cumulative exposure to toxic metals during fetal development and early
      infancy, so this study suggests that children with autism had a higher body
      burden of mercury during fetal/infant development. Antibiotic use is known to
      almost completely inhibit excretion of mercury in rats due to alteration of gut
      flora. Thus, higher use of oral antibiotics in the children with autism may have
      reduced their ability to excrete mercury, and hence may partially explain the
      higher level in baby teeth. Higher usage of oral antibiotics in infancy may also
      partially explain the high incidence of chronic gastrointestinal problems in
      individuals with autism.

PMID- 17497417
TI  - Organ growth functions in maturing male Sprague-Dawley rats based on a collective
      database.
AB  - Ten different organ weights (liver, spleen, kidneys, heart, lungs, brain,
      adrenals, testes, epididymes, and seminal vesicles) of male Sprague-Dawley (S-D)
      rats of different ages (1-280 d) were extracted based on a thorough literature
      survey database. A generalized Michaelis-Menten (GMM) model, used to fit organ
      weights versus age in a previous study (Schoeffner et al., 1999) based on a
      limited data, was used to find the best fit model for the present expanded data
      compilation. 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. Organ weights were significantly
      correlated with their respective ages for all organs and tissues. GMM-derived
      organ growth and percent body weight (%BW) fractions of different tissues were
      plotted against animal age and compared with experimental values as well as
      previously published models. The GMM-based organ growth and %BW fraction profiles
      were in general agreement with our empirical data as well as with previous
      studies. The present model was compared with the GMM model developed previously
      for six organs--liver, spleen, kidneys, heart, lungs, and brain--based on a
      limited data, and no significant difference was noticed between the two sets of
      predictions. It was concluded that the GMM models presented herein for different
      male S-D rats organs (liver, spleen, kidneys, heart, lungs, brain, adrenals,
      testes, epididymes, and seminal vesicles) are capable of predicting organ weights
      and %BW ratios accurately at different ages.

PMID- 17497418
TI  - Pediatric atomoxetine ingestions reported to Texas poison control centers, 2003
      2005.
AB  - Limited information exists on potentially adverse consequences following
      pediatric atomoxetine ingestions reported to poison control centers. Using
      pediatric atomoxetine ingestions reported to Texas poison control centers during
      2003-2005, the proportion of cases involving serious outcomes (medical outcomes
      classified as moderate effects, major effects, death, or judged as potentially
      toxic exposures) was determined for selected variables and evaluated for
      statistical significance by calculating the rate ratio (RR) and 95% confidence
      interval (CI). Of 501 cases identified, 31 (6%) involved serious outcomes. Higher
      serious outcome rates were found with a maximum dose of >2.8 mg/kg or >200 mg or
      >4 tablets. Serious outcome rates were also higher if the exposure involved
      intentional self-harm or the patient was already at or en route to a health care
      facility when the poison control center was contacted or referred to a health
      care facility by the poison control center. The severity of the outcome
      associated with pediatric atomoxetine ingestions was dependent upon the dose and
      the circumstances of the ingestion (whether intentional self-harm was involved).
      The management of patients with serious outcomes was more likely to involve
      health care facilities. This information is useful for creating triage guidelines
      for the management of pediatric atomoxetine ingestions.

PMID- 17497419
TI  - Novel bioactive constituents from Enhydra fluctuans LOUR.
AB  - A novel bioactive isoflavone glycoside 4',5,6,7-tetrahydroxy-8-methoxyisoflavone
      7-O-beta-D-galactopyranosyl-(1 --> 3)-O-beta-D-xylopyranosyl-(1 --> 4)-O-alpha-l
      rhamnopyranoside from the methanolic extract of the leaves of Enhydra fluctuans
      Lour. Its structure A was elucidated by various spectral analysis and chemical
      degradations. This compound exhibited microbial activity against various bacteria
      and fungi.

PMID- 17497420
TI  - Anthraquinones, Cdc25B phosphatase inhibitors, isolated from the roots of
      Polygonum multiflorum Thunb.
AB  - Three anthraquinones, Cdc25B phosphatase inhibitors, were isolated from the
      methanolic extract of the roots of Polygonum multiflorum Thunb. (Polygonaceae).
      Anthraquinones, physcion (1), emodin (2), and questin (3), inhibited the
      enzymatic activity of Cdc25B phosphatase with IC(50) values of 62.5, 30, and 34
      microg mL(-1), respectively. Emodin (2) and questin (3) strongly inhibited the
      growth of human colon cancer cells, SW620 with GI(50) values of 6.1 and 0.9
      microg mL(-1), respectively. Commercially available anthraquinones, chrysophanol
      (4), and rhein (5) also inhibited Cdc25B phosphatase with IC(50) values of 10.7
      and 22.1 microg mL(-1), respectively.

PMID- 17497421
TI  - A novel cycloartane triterpene glycoside from the seeds of Cassia sophera L.
AB  - A new cycloartane triterpene glycoside (1), named Cyclosophoside A, was isolated
      from the seeds of Cassia sophera L. The structure of 1 has been determined as 29
      O-beta-D-glucopyranoside of 1alpha, 3beta, 24xi, 25-tetrahydroxy-9, 19-cycloartan
      29-oic acid by means of physicochemical properties and spectroscopic methods (1D
      and 2D NMR, MS).

PMID- 17497422
TI  - A new bioactive triterpenoid saponin from the seeds of Lactuca scariola Linn.
AB  - A new triterpenoid saponin, 3-O-[beta-D-galactopyranosyl-(1 --> 3)-O-beta-D
      xylopyranosyl-(1 --> 4)-O-alpha-L-rhamnopyranosyl]-oleanolic acid; has been
      isolated from the seeds of Lactuca scariola. Its structure was determined by
      various spectral analysis and chemical degradations. This compound shows
      antimicrobial activity against various bacteria and fungi.

PMID- 17497423
TI  - Structural studies of a new acidic polysaccharide of apricot seeds.
AB  - This article reports the isolation and structural investigation of an acidic
      polysaccharide of the seeds of Prunus armeniaca (apricot) - a plant of commercial
      importance. The polysaccharide is composed of three sugars - mannose (50%),
      glucose (37.5%) and glucuronic acid (12.5%). The results of methylation analysis,
      partial depolymerisation, Smith degradation and NMR spectroscopic studies
      indicate a branched structure consisting of a straight chain of mainly alpha-(1 -
      > 3)mannan, which is interspersed with 4-O-(beta-D-mannopyranosyl)glucuronic acid
      residues. The side chain is bound to the alpha-mannan chain in the form of a
      trisaccharide of the glucose.

PMID- 17497424
TI  - Constituents of Cissus quadrangularis.
AB  - Two new iridoids 6-O-[2,3-dimethoxy]-trans-cinnamoyl catalpol (1) and 6-O-meta
      methoxy-benzoyl catalpol (2) along with a known iridoid picroside 1 (3), two
      stilbenes quadrangularin A (4) and pallidol (5), quercitin (6), quercitrin (7),
      beta-sitosterol (8) and beta-sitosterol glycoside (9) were isolated from Cissus
      quadrangularis Linn. The compounds 3 and 7 are first reported from this plant.
      The structures were elucidated by analysis of their spectroscopic data and by
      direct comparison with literature. This is the first reported occurrence of
      iridoids in C. quadrangularis.

PMID- 17497425
TI  - Quinones from plants of northeastern Brazil: structural diversity, chemical
      transformations, NMR data and biological activities.
AB  - The present review focus in quinones found in species of Brazilian northeastern
      Capraria biflora, Lippia sidoides, Lippia microphylla and Tabebuia serratifolia.
      The review cover ethnopharmacological aspects including photography of species,
      chemical structure feature, NMR datea and biological properties. Chemical
      transformations of lapachol to form enamine derivatives and biological activities
      are discussed.

PMID- 17497426
TI  - Dihydrochalcones with radical scavenging properties from the leaves of Syzygium
      jambos.
AB  - Chemical investigation of the dichloromethane extract of the leaves of Syzygium
      jambos furnished three dihydrochalcones, phloretin 4'-O-methyl ether (2',6'
      dihydroxy-4'-methoxydihydrochalcone) (1), myrigalone G (2',6'-dihydroxy-4'
      methoxy-3'-methyldihydrochalcone) (2), and myrigalone B (2',6'-dihydroxy-4'
      methoxy-3,5'-dimethyldihydrochalcone) (3) with radical scavenging properties
      towards the DPPH radical by spectrophotometric method.

PMID- 17497427
TI  - Identification of two meridianins from the crude extract of the tunicate Aplidium
      meridianum by tandem mass spectrometry.
AB  - As part of the development of an analytical technique for the detection of
      meridianins and related compounds in biological fluids, a crude extract of the
      tunicate Aplidium meridianum was analysed using neutral loss tandem mass
      spectrometry. The 41 u neutral loss-EI(+) mass spectrum showed molecular ions
      corresponding to two previously undetected alkaloids. We report herein the
      isolation and structure elucidation of these alkaloids, meridianins F and G.

PMID- 17497428
TI  - Synthesis of hydroxystilbenes and their derivatives via Heck reaction.
AB  - A group of differently substituted acetoxy- and methoxystilbenes were synthesised
      via Heck reaction. A comparison between the use--as coupling reagents--of
      iodobenzene derivatives and diazonium salts was performed. A successful microwave
      assisted demethylation by pyridine hydrochloride of some methoxystilbenes was
      carried out.

PMID- 17497429
TI  - Clopidogrel resistance--the cardiologist's perspective.
AB  - Platelet activation and aggregation play a major role in the pathogenesis of
      acute coronary syndromes. While clopidogrel has convincingly been shown to reduce
      atherothrombotic events in patients with acute coronary syndromes, and following
      percutaneous coronary interventions (PCI), a significant portion of patients
      continue to suffer cardiovascular events. A growing body of literature suggests
      that at least part of this treatment failure can be attributed to resistance to
      anti-thrombotic treatment in these patients. The purpose of this review is to
      clarify the current knowledge regarding clopidogrel resistance.

PMID- 17497430
TI  - Cloning of the cDNA for murine von Willebrand factor and identification of
      orthologous genes reveals the extent of conservation among diverse species.
AB  - Interaction of von Willebrand factor (VWF) with circulating platelets promotes
      hemostasis when a blood vessel is injured. The A1 domain of VWF is responsible
      for the initial interaction with platelets and is well conserved among species.
      Knowledge of the cDNA and genomic DNA sequences for human VWF allowed us to
      predict the cDNA sequence for murine VWF in silico and amplify its entire coding
      region by RT-PCR. The murine VWF cDNA has an open reading frame of 8,442 bp,
      encoding a protein of 2,813 amino acid residues with 83% identity to human pre
      pro-VWF. The same strategy was used to predict in silico the cDNA sequence for
      the ortholog of VWF in a further six species. Many of these predictions diverged
      substantially from the putative Reference Sequences derived by ab initio methods.
      Our predicted sequences indicated that the VWF gene has a conserved structure of
      52 exons in all seven mammalian species examined, as well as in the chicken.
      There is a minor structural variation in the pufferfish Takifugu rubripes insofar
      as the VWF gene in this species has 53 exons. Comparison of the translated amino
      acid sequences also revealed a high degree of conservation. In particular, the
      cysteine residues are conserved precisely throughout both the pro-peptide and the
      mature VWF sequence in all species, with a minor exception in the pufferfish VWF
      ortholog where two adjacent cysteine residues are omitted. The marked
      conservation of cysteine residues emphasizes the importance of the intricate
      pattern of disulfide bonds in governing the structure of pro-VWF and regulating
      the function of the mature VWF protein. It should also be emphasized that many of
      the conserved features of the VWF gene and protein were obscured when the
      comparison among species was based on the putative Reference Sequences instead of
      our predicted cDNA sequences.

PMID- 17497431
TI  - Variables influencing Multiplate(TM) whole blood impedance platelet aggregometry
      and turbidimetric platelet aggregation in healthy individuals.
AB  - We investigated the relationship between impedance platelet aggregometry (IPA) as
      measured by the Multiplate system and turbidimetric platelet aggregation (TPA)
      induced by ADP, arachidonic acid (AA), and collagen; blood cell counts; platelet
      function analyzer (PFA-100) closure times (CT), and von Willebrand factor (VWF)
      in 120 well-characterized healthy individuals. Pre-analytical and analytical
      conditions were standardized comprehensively. Analytical reliability of IPA and
      TPA and the influence of pre-analytical variables on assay results were also
      examined. IPA and TPA did not change significantly between 0.5 and 5 hours after
      blood collection when samples were stored at room temperature. TPA and IPA showed
      significantly greater intra-assay imprecision than respective TPA induced by the
      same agonists. Intra-individual variation did not differ significantly between
      IPA and TPA. The lower limits of reference range (2.5th percentiles) of AAIPA,
      ADPIPA and collagen IPA determined AM were 37, 20 and 40 AU, respectively. ADPIPA
      showed significantly lower maximum aggregation values than AAIPA and collagen IPA
      (P < 0.0001). There were no significant differences in any parameter between
      males and females. No significant differences between blood group 0 and non-0
      individuals were noted with respect to IPA and TPA. IPA did not change
      significantly during the day. In contrast, TPA measured PM was significantly
      lower than corresponding values determined a.m. (p < 0.0001). CEPI-CT, CADP-CT
      and leukocyte counts increased significantly from a.m. to p.m. (P = 0.008 and P >
      0.0001, respectively). Donors had significantly greater IPA induced by any
      agonist than non-donors (P-values < 0.0001, 0.0001 and 0.001, respectively),
      whereas TPA was not significantly different between donors and non-donors. IPA
      did not correlate significantly with TPA nor with PFA-100 CT. ADPIPA and collagen
      IPA correlated significantly with platelet count. TPA was not associated with
      platelet count. An inverse significant correlation was observed between TPA
      induced by any agonist and leukocyte count, whereas leukocyte count did not
      influence IPA. CEPI-CT and CADP-CT correlated significantly with VWF:CBA and with
      each other but not with TPA. We concluded that IPA and TPA measure different
      aspects of platelet function. IPA results reflect interactions between platelets,
      red and white cells, while TPA does not. This explains discrepancies in
      associations of IPA and TPA with cell counts, time of day and blood donation. The
      clinical significance of IPA determined using the Multiplate device remains to be
      determined in studies on patients with platelet dysfunction and under treatment
      with antiplatelet agents.

PMID- 17497432
TI  - Regulation of plasma membrane Ca2+-ATPase in human platelets by calpain.
AB  - The plasma membrane Ca(2+)-ATPase (PMCA) plays an essential role in maintaining
      low cytosolic Ca(2+) in resting human platelets by extruding Ca(2+) from the
      cytoplasm across the plasma membrane. Since PMCA is the main agent of Ca(2+)
      efflux in platelets, it is a key point for regulation of platelet Ca(2+)
      metabolism. PMCA has been shown to be an excellent substrate for the Ca(2+)
      activated cysteine protease calpain, a major platelet protein that is turned on
      during platelet activation. The objectives of the present work were to determine
      if PMCA is degraded during thrombin- and collagen-mediated platelet activation,
      and if calpain is responsible. The kinetics of PMCA degradation during platelet
      activation were analysed using SDS polyacrylamide gel electrophoresis and
      immunoblotting. The role of calpain was tested using the calpain inhibitors
      calpeptin and ALLN. Platelet activation mediated by both collagen and thrombin
      resulted in degradation of 60% of platelet PMCA within 18 minutes. Calpeptin and
      ALLN significantly inhibited the rate and extent of PMCA degradation. We conclude
      that calpain-mediated degradation of PMCA during platelet activation likely
      contributes significantly to Ca(2+) regulation and, therefore, to platelet
      function.

PMID- 17497433
TI  - The effect of weight loss on the mean platelet volume in obese patients.
AB  - Obesity is a chronic metabolic disorder associated with cardiovascular disease
      and atherosclerosis. Platelet activation and aggregation are central processes in
      the pathophysiology of cardiovascular disease. Mean platelet volume (MPV), a
      determinant of platelet activation, is a newly emerging risk marker for
      atherothrombosis. Our objective was to evaluate the effect of weight loss on the
      MPV in obese patients. We selected 30 obese women patients and 30 non-obese
      healthy women subjects. All obese patients took the same content and caloric diet
      treatment for 3 months. Body mass index (BMI), metabolic parameters and MPV were
      measured at baseline and after 3 months diet treatment. Before diet treatment,
      obese group had significantly higher MPV levels than in the non-obese control
      group (8.18 +/- 1.09 fl vs. 8.01 +/- 0.95 fl, p = 0.004). MPV showed positive
      correlations with BMI level in the obese group (r = 0.43, p = 0.017). BMI
      significantly decreased after diet treatment (36.2 +/- 3.2 kg/m(2) vs. 34.7 +/-
      3.6 kg/m(2), p < 0.001), in the obese group. MPV significantly decreased after
      diet treatment in the obese group (8.18 +/- 1.09 fl vs. 8.08 +/- 1.02 fl, p =
      0.013). There was a positive correlation between weight loss and reduction in MPV
      (r = 0.41, p = 0.024). In addition to its well-known positive effects on
      cardiovascular disease risk, weight loss may also possess significant anti
      platelet activation properties that can contribute its antiatherogenic effects in
      obese patients.

PMID- 17497434
TI  - Alternative splice variants of phospholipase C-beta2 are expressed in platelets:
      effect on Galphaq-dependent activation and localization.
AB  - Phospholipase C (PLC) beta2 plays a pivotal role in G-protein dependent signal
      transduction in platelets. We have previously demonstrated in platelets,
      leukocytes and human erythroleukemia cells the presence of transcripts of two
      forms of PLC-beta2 generated by alternative splicing. They differ by 45
      nucleotides in the carboxyl-terminal region and are designated as PLC-beta2a and
      PLC-beta2b, with and without by 15 amino acid residues (corresponding to 864
      878). The presence of the two variants has not been shown at the protein level in
      cells. Moreover, the carboxy-terminal region of PLC-beta has been implicated in
      Galphaq activation, particulate association, and nuclear localization, suggesting
      that the PLC-beta2 splice variants may be regulated differentially. We
      demonstrate for the first time that both PLC-beta2 isoforms are expressed in
      platelets at the protein level. Studies in CV-1 cells transfected with PLC-beta2a
      or beta2b cDNAs, along with constitutively activated Galphaq (Q209L), showed that
      inositolphosphate formation was comparable between the two variants. However, the
      nuclear localization of the two isoforms was different with a higher cytoplasmic
      to nuclear ratio for PLC-beta2b compared to PLC-beta2a, suggesting that a great
      proportion of the total PLC-beta2a was in the nucleus relative to PLC-beta2b.
      There was no difference in the relative distribution of the two variants between
      the cytosol and particulate fractions. Both PLC-beta2 alternative splice variants
      are expressed at the protein level in platelets. In transfected CV-1 cells, PLC
      beta2a is relatively more enriched in the nuclei than PLC-beta2b suggesting that
      the two variants may have different effects in cell proliferation and
      differentiation.

PMID- 17497435
TI  - Role of dietary polyphenols in platelet aggregation. A review of the
      supplementation studies.
AB  - Epidemiological studies suggest that high polyphenols intake from diet is
      associated with reduced risk for cardiovascular diseases. Platelet aggregation is
      a crucial mechanism in the pathogenesis and clinical expression of coronary acute
      syndrome, and there is extensive evidence that antiplatelet therapy reduces
      cardiovascular disease risk. In this review, the available literature on the
      effect of polyphenols supplementation on platelet aggregation in humans or animal
      models has been critically analyzed, taking into consideration the different
      experimental protocols employed. In some studies, polyphenols supplementation did
      not show any effect on platelet aggregation. However, in the most of the studies,
      polyphenols supplementation, either as purified compounds or food extracts,
      showed some inhibitory effects, both in humans and in animal models. The extent
      of the inhibition varies in a wide range, depending on the experimental
      conditions used. The observed inhibitory effect of polyphenols on platelet
      aggregation might explain, at least in part, the epidemiological data on
      beneficial effect of dietary polyphenols on cardiovascular disease risk and
      suggests a role for polyphenols in helping to prevent cardiovascular diseases.

PMID- 17497436
TI  - Nitric oxide regulates expression of sonic hedgehog and hypoxia-inducible factor
      1alpha in an experimental model of kidney ischemia-reperfusion.
AB  - This study was designed to determine the effect of L-arginine on hypoxia
      inducible factor alpha (HIF-1 alpha) and Sonic hedgehog (Shh) levels considered
      to be involved in the development of ischemia/reperfusion (I/R) injury.
      Unilaterally nephrectomized Sprague-Dawley rats were subjected to 60 minutes of
      left renal ischemia followed by 45 minutes of reperfusion. Group 1 were sham
      operated animals; group 2, I-R/Untreated animals; and group 3, I-R/L-Arg-treated
      animals. Serum creatinine, blood urea nitrogen (BUN), and kidney malondialdehyde
      (MDA) levels were determined as well as examining the kidneys histologically. The
      treatment of rats with L-Arg produced a significant reduction in the levels of
      BUN, creatinine, MDA, and histopathological score compared to renal I/R groups.
      The Shh expression in the tubulus epithelia were intensely increased in the I-R/L
      Arg group when compared to that of the Sham-control and the I-R/untreated groups.
      Additionally, the HIF-1alpha expression in the tubulus epithelia and the
      interstitial spaces were intensely increased in the I-R/L-Arg group. These
      findings suggest that NO reduces the renal dysfunction associated with I/R of the
      kidney and may act as a trigger to induce Shh and HIF-1 activity.

PMID- 17497437
TI  - Effects of different doses of hyperbaric oxygen on cisplatin-induced
      nephrotoxicity.
AB  - Cisplatin, an effective antineoplastic agent, frequently induces acute renal
      failure in animals and humans. Hyperbaric oxygen (HBO) has been shown to prevent
      cisplatin-induced nephrotoxicity in rats. This study investigated the effect of
      two different HBO regimes on renal functions, oxidative stress, and
      histopathological changes in rat kidneys after cisplatin treatment. Wistar rats
      were divided into five groups: control, HBO, cisplatin, cisplatin plus once daily
      HBO, and cisplatin plus twice daily HBO. Cisplatin was given as a single
      intraperitoneal dose of 6 mg/kg, and HBO was applied for 60 min at 2.5 atm for
      six days. HBO alone did not alter any biochemical parameters or histopathological
      findings compared with the control group. Cisplatin increased serum urea and
      creatinine levels and caused severe histopathological injury. In addition,
      cisplatin increased lipid peroxidation and impaired superoxide dismutase (SOD)
      and glutathione peroxidase (GSH-Px) activities in kidney tissue. Once daily HBO
      after cisplatin treatment slightly reduced serum urea and creatinine levels and
      attenuated histopathological injury. HBO also reduced lipid peroxidation and
      increased SOD and GSH-Px activities significantly. Although twice daily HBO was
      determined to be more effective than once daily HBO on oxidative stress
      parameters, it increased serum creatinine levels and histopathological injury
      compared with the cisplatin group. It was concluded that HBO alone does not
      induce nephrotoxicity and oxidative stress in rat kidneys; once daily HBO may
      prevent cisplatin-induced nephrotoxicity, an effect that is partially mediated by
      the modification of oxidant/antioxidant systems in the kidneys; and twice daily
      HBO potentiates cisplatin nephrotoxicity by a ROS-independent mechanism.

PMID- 17497438
TI  - Comparison of azithromycin and oral hygiene program in the treatment of
      cyclosporine-induced gingival hyperplasia.
AB  - BACKGROUND: It has been shown that azithromycin improves cyclosporine-induced
      gingival hyperplasia (GH), but its efficacy was never compared against an
      efficient oral hygiene program (OHP). The aim of this study was to analyze the
      effects of azithromycin plus OHP versus OHP alone in patients with cyclosporine
      induced GH. METHODS: After periodontal evaluation, 20 renal transplant recipients
      received detailed oral hygiene instructions and a complete OHP, and were
      randomized to control (OHP) or azithromycin groups (OHP plus azithromycin).
      Patients were re-evaluated after 15 and 30 days. Both groups were similar in time
      after transplant, age, gender, cyclosporine dose, and cyclosporine through level
      and serum creatinine. The control group had fewer patients using calcium cannel
      blockers (10% vs. 70%, p = 0.02). RESULTS: All patients improved in pain,
      halitosis, and gum bleeding after OHP. The control group did not improve plaque
      index (PI) or GH. In contrast, baseline PI decreased from 1.52 +/- 0.28 to 0.50
      +/- 0.16 on day 15 (p < 0.01) and to 0.46 +/- 0.14 on day 30 (p < 0.01) in the
      azithromycin group, and the GH score decreased from 1.9 +/- 0.27 to 0.90 +/- 0.27
      on day 15 (p < 0.05) and to 0.70 +/- 0.21 on day 30 (p < 0.01). CONCLUSION:
      Azithromycin associated to efficient OHP induced a striking reduction in
      cyclosporine-induced GH, while efficient OHP alone improved oral symptoms but did
      not decrease cyclosporine-induced GH.

PMID- 17497439
TI  - Iloprost for additional anticoagulation in continuous renal replacement therapy-
      a pilot study.
AB  - PURPOSE: The aim of this pilot study was to compare the effect of heparin
      anticoagulation with and without iloprost administration during continuous renal
      replacement therapy (CRRT) in critically ill patients. MATERIAL AND METHODS: In a
      prospective, randomized, controlled pilot study at an intensive care unit at a
      university hospital, 20 patients requiring CRRT were investigated. Patients were
      allocated into two groups: group 1, the heparin group; and group 2, the heparin
      plus 1 ng/kg/min iloprost. In both groups, activated partial thromboplastin time
      (aPTT) was adjusted to 40-50 sec. Observation time was a maximum of 7 days.
      RESULTS: Median filter run time was significantly prolonged by iloprost
      administration to a median of 14 h (13-26 h) compared to 10 h (4-12 h) in the
      heparin group (p = 0.004). A decrease in platelet count was attenuated by
      iloprost administration (p = 0.012). There were no bleeding complications in
      either group. Hemofiltration efficiency did not differ significantly between the
      groups. CONCLUSION: Additional administration of iloprost prolonged the filter
      run time of continuous veno-venous hemofiltration (CVVH) in this setting and
      attenuated the fall in platelet count during CRRT.

PMID- 17497440
TI  - Urinary excretion of creatol, an in vivo biomarker of hydroxyl radical, in
      patients with chronic renal failure.
AB  - Creatol (CTL) is a hydroxyl radical adduct of creatinine (Cr). The serum
      methylguanidine (MG) level and the MG/Cr molar ratio are reported to be
      biomarkers for oxidative stress. The aim of this study was to examine whether
      urinary excretion of CTL, another oxidative stress-related marker, is increased
      in patients with chronic renal failure (CRF). One hundred twenty-four non
      dialyzed patients with chronic renal failure (serum Cr level, 1.3-10.0 mg/dL)
      were recruited from our hospitals. Urine and serum levels of CTL and MG were
      determined by high-performance liquid chromatography with the use of 9, 10-
      phenanthrenequinone as a fluorogenic reagent. The CTL/Cr and (CTL+MG)/Cr molar
      ratios in spot urine samples were also compared with those in 24-h urine samples.
      The urinary CTL/Cr and (CTL+MG)/Cr molar ratios increased with decreases in Cr
      clearance in patients with CRF. Correlations between serum and spot urine
      (CTL+MG)/Cr and between serum and spot urine CTL/Cr were quite similar to those
      in 24-h urine samples. CTL/Cr and (CTL+MG)/Cr molar ratios in both 24-h urine and
      spot urine samples appear to be useful indices of the severity of CRF.

PMID- 17497441
TI  - Low dose intradermal vaccination is superior to high dose intramuscular
      vaccination for hepatitis B in unresponsive hemodialysis patients.
AB  - After two intramuscular (IM) vaccination protocols (40 microg at 0, 1, 2, and 6
      months), patients who were unresponsive to hepatitis B vaccination were collected
      from three HD centers. The aim of this study was to compare the effectiveness of
      intradermal (ID) and repeated IM vaccination protocols. Thirty-three of 639 HD
      patients were found to be unresponsive. Patients were randomly assigned into two
      groups: one to receive 80 microg ID and the other 160 microg IM vaccination
      protocol. Both ID (p = 0.000) and IM (p = 0.03) groups disclosed statistically
      significant seroconversion rates six months after the last vaccination dose. The
      seroconversion rate was 94.1% in the ID and 50% in the IM groups - showing a
      significant improvement in the ID group (p = 0.011). A low-dose ID is superior to
      standard IM vaccination protocol and also more cost-effective in unresponsive HD
      patients.

PMID- 17497442
TI  - Icodextrine and insulin resistance in continuous ambulatory peritoneal dialysis
      patients.
AB  - Insulin resistance is commonly observed in uremic patients. Glucose-based
      peritoneal dialysis solutions have long-term metabolic complications like
      hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to
      examine the insulin resistance in patients undergoing continuous ambulatory
      peritoneal dialysis (CAPD) with standard glucose and icodextrin containing
      solutions. The entire non diabetic CAPD patients of our center were studied:
      forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months.
      Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years
      were treated with standard glucose solutions (glucose group). The other 17
      patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated
      with standard glucose solutions during the day and icodextrin dwell during the
      night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting
      serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87
      in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores
      of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p =
      0.025) than the icodextrin group. A significant positive correlation of HOMA
      score with insulin, fasting plasma glucose, and triglyceride levels were found in
      HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15
      patients of the glucose group (88%) were hypertensive, but there was no
      statistically significant difference between the two groups (p = 0.13). The
      groups showed no significant differences for body mass index and serum levels of
      glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol,
      triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion,
      the use of icodextrin in the long nighttime dwell can reduce serum insulin levels
      and increase insulin sensitivity in CAPD patients.

PMID- 17497443
TI  - Imaging modalities for renal artery stenosis in suspected renovascular
      hypertension: prospective intraindividual comparison of color Doppler US, CT
      angiography, GD-enhanced MR angiography, and digital substraction angiography.
AB  - The aim of the study was to evaluate the diagnostic accuracy of Color Doppler US,
      CT Angiography (CTA), and GD-enhanced MR Angiography (MRA) compared with digital
      subtraction angiography (DSA) for the detection of renal artery stenosis in
      patients with clinically suspected renovascular hypertension. Fifty-eight
      patients with suspected renovascular hypertension were enrolled in the study. All
      patients underwent Color Doppler US, CTA and GD-enhanced MRA. DSA was the gold
      standard method for the number of renal arteries, existence and degree of
      stenosis, or evidence of fibromuscular dysplasia. DSA depicted 132 renal
      arteries, 16 stenoses, and 4 arteries with fibromuscular dysplasia. Color Doppler
      US failed to detect 1 main and 14 polar arteries. CTA depicted all main renal
      arteries and 7/16 polar arteries, but failed to detect stenosis in two accessory
      vessels. Likewise, MRA did not detect stenotic accessory renal arteries, depicted
      9/16 polar renal arteries, but missed two main renal arteries. All methods
      depicted the four main renal arteries with fibromuscular dysplasia. The overall
      sensitivity, specificity, and positive and negative predictive accuracy were 75%,
      89.6%, 60% and 94.6%, respectively, for color Doppler US; 94%, 93%, 71%, and 99%,
      respectively, for CTA; and 90%, 94.1%, 75%, and 98%, respectively, for GD
      enhanced MRA. CTA and GD-enhanced MRA have comparable and satisfactory results
      with respect to the negative predictive accuracy of the suspected renal artery
      stenosis. The concept of an imaging algorithm including US as screening test when
      appropriate and CTA or MRA as the second step-procedure is suggested. Therefore,
      DSA may be reserved for cases with major discrepancies or therapeutic
      interventions.

PMID- 17497444
TI  - Predictors of left ventricular hypertrophy in patients with chronic kidney
      disease.
AB  - The aim of the present study is to determine the prevalence and predictors of
      left ventricular hypertrophy in patients with stage 3 or 4 chronic kidney
      disease. Thirty-four patients were included. In addition to hematological and
      biochemical evaluations, echocardiography and ambulatory blood pressure
      monitoring were performed both at the beginning and at the end of the first year.
      Echocardiographic left ventricular mass was calculated and indexed to body
      surface area to calculate left ventricular mass index (LVMI). Left ventricular
      hypertrophy was diagnosed if LVMI >131 g/m(2) in male and >100 g/m(2) in female
      patients. During the follow-up period, estimated glomerular filtration rate
      decreased from 36.6+/-11.7 to 31.0+/-14.0 mL/min (p = 0.03), while LVMI increased
      from 130.2+/-35.6 to 140.5+/-30.5 g/m(2) (p = 0.055). Left ventricular
      hypertrophy was detected in 67.6% of the patients at the baseline and in 89.7% at
      the end of the study (p = 0.011). The independent predictors of the final LVMI
      were age (p = 0.035), baseline day-time systolic blood pressure (p = 0.01),
      baseline C-reactive protein (p = 0.001), and the decrease in glomerular
      filtration rate during the follow-up (p = 0.002). Left ventricular hypertrophy is
      quite frequent among patients with stage 3 or 4 chronic kidney disease, and its
      prevalence increases while glomerular filtration rate decreases during the follow
      up. The early detection of left ventricular hypertrophy and both prevention of
      the deterioration of renal function and aggressive blood pressure control may
      help to achieve a decrease in cardiovascular morbidity and mortality in these
      patients.

PMID- 17497445
TI  - Effect of peritoneal dialysis solution type on serum lipid levels in end-stage
      renal disease.
AB  - Among the different cardiovascular risk factors, lipid abnormalities dominate the
      high mortality in chronic ambulatory peritoneal dialysis patients. So far, no
      data comparing the effect of standard glucose-containing, amino acid-containing,
      and icodextrin-containing peritoneal dialysis solutions on serum lipid
      concentrations in a chronic ambulatory peritoneal dialysis population are
      available. To determine the effect of peritoneal dialysis solutions on parameters
      of lipid metabolism, 67 subjects who had continued their usual dialysis for the
      last six months were enrolled in the study. Group A consisted of 18 patients who
      were receiving only glucose-based peritoneal dialysis solutions, group B
      consisted of 18 patients who were receiving glucose and amino acid-based
      peritoneal dialysis solutions, and group C consisted of 31 patients who were
      receiving glucose and icodextrin-based peritoneal dialysis solutions. Serum lipid
      parameters including total cholesterol, low-density lipoprotein, high-density
      lipoprotein, triglyceride, and lipoprotein (a) were determined in all groups. No
      significant difference in serum lipid parameters was found between groups A, B,
      and C. These results demonstrate the lack of the effect of amino acid or
      icodextrin-based peritoneal solutions on dyslipidemia of CAPD patients.

PMID- 17497446
TI  - The effect of dialytic modalities on clinical outcomes in ESRD patients with
      familial Mediterranean fever.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease
      seen primarily in Sephardic Jews, Turks, and Armenians. The disease manifests as
      recurrent attacks of fever and serositis. The most important complication of FMF
      is the development of renal failure due to AA type amyloidosis. There has not
      been extensive experience with renal replacement therapy in FMF amyloidosis.
      Nevertheless, there may be a concern about the possibility of higher rates of
      morbidity and mortality in amyloidotic patients maintained on chronic
      hemodialysis. Moreover, there is not enough experience regarding patients on
      chronic peritoneal dialysis. As a result, the best treatment modality of end
      stage renal disease (ESRD) in these circumstances still remains unclear. This
      study aimed to compare the effect of hemodialysis and peritoneal dialysis
      modalities on clinical outcomes in ESRD patients associated with FMF amyloidosis.
      METHODS: Forty FMF patients with ESRD due to amyloidosis were retrospectively
      analyzed. All 40 patients were on renal replacement therapy, 20 on hemodialysis
      (HD), 20 on peritoneal dialysis (PD). Peritoneal solute transport rates, weekly
      mean creatinine clearance, and daily mean ultrafiltration (UF) of the patients on
      chronic peritoneal dialysis were evaluated. Weekly dialysis durations, dialysis
      membrane properties, Kt/V values, interdialytic weight gains, and frequency of
      hypotension during dialysis were evaluated on hemodialysis patients. All of the
      patients were examined according to their demographic characteristics, laboratory
      results, duration time on dialysis, erythropoietin requirements, frequencies of
      infectious complications requiring hospitalization, and the two renal replacement
      modalities mentioned above were compared in terms of these parameters. RESULTS:
      Serum albumin levels of the patients with FMF amyloidosis who were maintained on
      peritoneal dialysis treatment were lower (2.87 vs 3.45) and the frequency of
      infections of the same group was higher (4.2 vs 0.5) than the patients with ESRD
      secondary to other diseases in the CAPD group. CONCLUSIONS: This retrospective
      analysis showed that peritoneal dialysis may have some disadvantages in
      amyloidotic patients. Due to the high frequency of hypoalbuminemia and infectious
      complications seen in this group, peritoneal dialysis is widely accepted as an
      alternative choice of treatment when hemodialysis is not appropriate.

PMID- 17497447
TI  - Effects of N-3 PUFAs supplementation on insulin resistance and inflammatory
      biomarkers in hemodialysis patients.
AB  - AIMS/HYPOTHESIS: It was suggested that polyunsaturated n-3 fatty acids (n-3
      PUFAs) could improve insulin sensitivity and have an anti-inflammatory effects in
      overall population. This study investigates a possible effect of n-3 PUFAs
      supplementation on the insulin sensitivity and some inflammatory markers; hence,
      patients with chronic renal failure (CRF) on maintenance hemodialysis (MHD) are
      presented with insulin resistance. METHODS: This study explored the ratio between
      red blood cells (RBC) phospholipid long chain fatty acids (LC FAs) and components
      of metabolic syndrome (MeS) in 35 patients (mean age 54.50 +/- 11.99 years) with
      CRF on MHD. Furthermore, the effects of omega-3 FA eight-week's supplementation
      (EPA+DHA, 2.4 g/d) on the MeS features and inflammatory markers TNF-alpha, IL 6,
      and hsCRP were examined. RESULTS: Supplementation increased EPA and DHA levels in
      RBCs (p = 0.009 for EPA and p = 0.002 for DHA). Total n-6 PUFAs: n-3 PUFAs ratio
      tended to be lower after supplementation (p = 0.31), but not significantly. Data
      revealed a significant decrease of saturated FAs (SFA) (p = 0.01) as well as
      total SFA: n-3 PUFAs ratio during the treatment (p = 0.04). The values of serum
      insulin and calculated IR index-IR HOMA were reduced after supplementation (p =
      0.001 for both). There was a significant decrease in the levels of all
      inflammatory markers (p = 0.01 for TNF alpha, p = 0.001 for IL 6, p = 0.001 for
      hsCRP, and p = 0.01 for ferritin). In multivariate regression analysis, only the
      changes in n-6 PUFAs: n-3 PUFAs ratio independently contributed to 40% of the
      variance in IR HOMA. The impact of changes in PUFAs level in RBCs membrane
      phospholipid fatty acids on inflammation markers was also registered. The changes
      in n-6: n-3 PUFAs ratio independently contributed to 18% of the variance in TNF
      alpha. CONCLUSION: It was concluded that the EPA and DHA moderate dose
      administration in the patients with CRF on MHD had a beneficial effect on insulin
      resistance decrease. The anti-inflammatory effects of the supplemented PUFAs were
      also presented.

PMID- 17497448
TI  - Prevalence and predictors of arrhythmia in end stage renal disease patients on
      hemodialysis.
AB  - BACKGROUND: Sudden death is common in end-stage renal disease (ESRD). Cardiac
      arrhythmia is observed frequently in patients with ESRD and is thought to be
      responsible for this high rate of sudden death. This study investigated the
      prevalence and the predictors of arrhythmia in patients on maintenance dialysis.
      METHODS: Ninety-four patients on hemodialysis program were enrolled in the study.
      Routine laboratory results were noted. Arrhythmia, periods of silent ischemia,
      and heart-rate variability analyses were obtained from 24-hour Holter monitor
      recordings. Corrected QT (QTc) dispersion was calculated from 12-lead surface
      EKG. Echocardiographic and tissue Doppler examinations were performed on
      interdialytic days as well. Ventricular arrhythmia was classified according to
      Lown classification; classes 3 and above were accepted as complex ventricular
      arrhythmia (CVA). RESULTS: The mean age was 52.5+/-13.2 years; 44 (46.8%) were
      women. Ventricular premature contractions were detected in 80 (85.1%) patients,
      of whom 35 (37.2%) were classified as complex ventricular arrhythmia (CVA).
      Coronary artery disease, hypertension, and QTc dispersion appeared as independent
      factors predictive of CVA development. Atrial premature contractions (APC) were
      detected in 53 patients (56.4%) and supraventricular arrhythmia in 15 (16%)
      patients; all were identified as atrial fibrillation. Duration of dialysis
      therapy was found as an independent predictor of APC. CONCLUSION: Arrhythmia is
      frequently observed in ESRD patients receiving hemodialysis and may be
      responsible for the high rate of sudden mortality. Hypertension, CAD, and QTc
      dispersion are independent predictors of CVA, and duration of dialysis therapy is
      an independent factor affecting APC development in these patients.

PMID- 17497449
TI  - Acute effects of intermittent hemodialysis and sustained low-efficiency
      hemodialysis (SLED) on the pulmonary function of patients under mechanical
      ventilation.
AB  - The effects of hemodialysis (HD) on pulmonary function are still controversial.
      The objective of this study was to evaluate the effect of intermittent
      hemodialysis (IHD) and sustained low-efficiency dialysis (SLED) on the
      respiratory mechanics of ICU patients under invasive mechanical ventilation. We
      prospectively studied 31 patients. Laboratory and respiratory evaluation (static
      and dynamic compliance and resistance) was performed pre- and post-HD. Forty HD
      sessions were studied and grouped in: SLED (n = 17; Qa = 200-250 mL/min, Qd = 300
      mL/min) and IHD (n = 23; Qa = 250-300 mL/min, Qd = 500 mL/min). There was no
      difference between the groups according to age, gender, comorbidities, APACHE II,
      and cause of mechanical ventilation, but pre-HD, patients in the IHD group had
      higher levels of plasma creatinine (5.4 +/- 2.0 vs. 4.2 +/- 1.3 mg/dL, p = 0.048)
      and platelets (286 +/- 186 vs. 174 +/- 95 10(3)/mm(2), p = 0.032) and lower
      arterial pH (7.37 +/- 0.07 vs. 7.42 +/- 0.05, p = 0.02). The efficiency of the
      treatment was similar (p > 0.05) with both types of HD regarding fluid removal,
      urea reduction rate, and decrease in plasma creatinine. Pre-HD, the ventilatory
      conditions of both groups were similar (p > 0.05) except for pressure support
      ventilation and airflow resistance. There were no changes (pre- versus post-HD p
      > 0.05) induced either by IHD or SLED in the ratio PaO(2)/FiO(2) or in any
      measured ventilatory parameter. In conclusion, neither IHD nor SLED modifies the
      pulmonary function of patients under mechanical ventilation.

PMID- 17497450
TI  - Defining peritoneal dialysis adequacy: Kt/Vurea revisited.
AB  - BACKGROUND: Although adequate peritoneal dialysis is not well defined, Kt/Vurea
      has been used as an index, and various values have been proposed. However,
      conflicting evidence existed regarding the appropriateness of using Kt/Vurea to
      define dialysis adequacy and its optimal value. Therefore, the present study
      performed a theoretical analysis on whether we should use Kt/Vurea to define
      peritoneal dialysis adequacy and what the optimal value should be. METHODS: The
      three-pore model was applied to evaluate the transport patterns of different
      molecular weight solutes and fluid. Optimal Kt/Vurea value was estimated based on
      urea kinetics and nitrogen balance. RESULTS: The removal pattern of small solute,
      middle and large molecules, and fluid and sodium are quite different. Depending
      on the dwell time, higher urea removal does not necessarily mean higher sodium,
      fluid, and other molecular weight solute removals. To reach nitrogen balance, the
      dialysis doses and therefore Kt/Vurea values varied with different dietary
      protein intakes in a patient with a given weight and residual renal function.
      CONCLUSION: This study shows that Kt/Vurea in peritoneal dialysis cannot
      represent the removal of other solutes and fluid, indicating that Kt/Vurea alone
      should not be used as a sole indicator of peritoneal dialysis adequacy. The
      results also show that optimal Kt/Vurea cannot be a fixed value, but varies
      according to individual dietary protein intake and tolerable blood urea level.

PMID- 17497451
TI  - Chronic exposure of human glomerular epithelial cells to high glucose
      concentration results in modulation of high-affinity glucose transporters
      expression.
AB  - INTRODUCTION: GLUTs are specific membrane proteins that transport glucose down a
      concentration gradient. There have been few studies on their expression in the
      kidney. The aim of this study was to identify the expression of GLUTs 1, 3, and 4
      in HGEC and their regulation under diabetic milieu. MATERIAL AND METHODS: An
      immortalized cell line of HGEC was used. Cells were cultured in medium containing
      5 or 25 mM D-glucose. Western blotting and flow cytometry were used to examine
      the presence of GLUTs (1, 3, 4) and alterations in expression. RESULTS: Western
      blotting analysis revealed that GLUT-1 levels were increased by 53% in HGEC
      cultured under experimental diabetes compared to cells grown in 5mM glucose. GLUT
      3 levels were also increased by 15% under diabetic conditions. GLUT-4 levels were
      decreased by 20% in diabetes. Fluorescence Activated Cell Sorting (FACS) analysis
      demonstrated that cell surface expression of GLUT-1 was increased by 28% in cells
      grown in 25mM glucose. High glucose concentration did not affect cell surface
      expression of GLUT-3 and GLUT-4. DISCUSSION: These findings suggest that
      depressed GLUT4 expression in glomerulus and overexpression of GLUT-1 and in a
      lesser extent of GLUT-3 may alter the glucose uptake in these cells. It has been
      suggested that the overexpression of GLUT-1 in glomerulus, being the major
      isoform, may lead to the initial pathologic hallmarks of diabetic nephropathy.

PMID- 17497452
TI  - Varicella-zoster infection with encephalopathy, pneumonia, and renal failure: a
      case report.
AB  - Primary varicella-zoster (VZ) infection is rare in adults, but the rate of
      morbidity and mortality is higher than in children. Pneumonia is the most common
      complication of primary VZ infection in adults. Moreover, varicella pneumonia
      associated with acute renal failure and acute encephalopathy is very rare. This
      study reports on a case of disseminated VZ infection successfully treated with
      acyclovir. The patient was otherwise healthy and denied previous systemic or
      infectious disease. The initial diagnosis was varicella pneumonia. However,
      multiple organ involvement subsequently was found in several organs, including
      the kidney, brain, lung, liver, blood, and skin. The reactivation of VZ infection
      was strongly suspected. Abnormal renal and liver function and thrombocytopenia
      also were noted. The patient with chickenpox was treated successfully with
      acyclovir without complication. In conclusion, multiple organ involvement is a
      rare complication of VZ infection in adults. In the severe case presented here,
      adequate intravenous acyclovir administration and close observation of the
      general condition were essential for successfully treating disseminated VZ
      infection without complications.

PMID- 17497453
TI  - Successful treatment of focal segmental glomerulosclerosis in association with
      mantle cell lymphoma.

PMID- 17497454
TI  - Colchicine overdose-induced acute renal failure and electrolyte imbalance.
AB  - Colchicine has been used to control gouty arthritis for long time; colchicine
      overdose, however, causes multiple organ dysfunction. To date, no investigation
      has revealed the site of kidney lesion or dysfunction. This investigation
      describes the case of a male with a history of gout who ingested a large amount
      of colchicine and developed renal, hematopoietic, gastrointestinal, muscular,
      electrolytic, and hepatic disorder. Glucosuria was noted during hospital days.
      Colchicine intoxication is shown to induce proximal tubule damage. Severe
      electrolytes imbalance was noted, including hypomagnesemia, hypophosphatemia, and
      hypocalcemia. After management, the renal function and serum electrolyte of the
      patient recovered on the sixth day of hospitalization.

PMID- 17497455
TI  - Fatal cardiac tamponade in malarial acute renal failure.
AB  - Uremic hemorrhagic pericarditis occurs much less frequently in acute than in
      chronic renal failure, but when it does, it is a potentially fatal complication.
      The possibility of hemorrhagic pericarditis and cardiac tamponade should be
      considered in patients with acute renal failure and acute hemodynamic
      instability. This study reports a case of falciparum malaria complicated by acute
      renal failure that developed fatal cardiac tamponade in the recovery phase of
      acute renal failure.

PMID- 17497456
TI  - A fatal case of paraquat poisoning following minimal dermal exposure.
AB  - Paraquat is a pesticide widely used in agriculture. Numerous cases of paraquat
      intoxication have been reported either accidentally or intentionally as a
      suicidal attempt. The most severe cases of paraquat poisoning refer to oral
      ingestion. Complications include respiratory, hepatic, and renal failure, and are
      usually fatal. Dermal exposure is less frequent and rarely fatal. This article
      reports a case of an 81-year-old man with minimal skin burn after accidental
      paraquat exposure. The patient developed acute renal and respiratory failure and,
      despite aggressive treatment with hemodialysis, hemoperfusion, and mechanical
      ventilation, died two days later.

PMID- 17497457
TI  - Experimental models of acute renal failure and erythropoietin: what evidence of a
      direct effect?
AB  - The kidney can achieve a structural and functional recovery after the damage
      induced by ischemia and reperfusion. This is due to the regeneration of
      epithelial tubular cells, the intervention of immature cells mainly localized in
      the medulla, and a small number of bone marrow-derived stem cells. In many
      instances, however, recovery is delayed or does not occur at all. The mechanisms
      allowing the renal cells to de-differentiate still need to be clarified in order
      to find a therapeutic approach that can amplify this ability and then stop the
      fibroid involution and the progression toward renal failure. Several authors have
      hypothesized a protective effect of EPO against ischemic and cytotoxic renal
      damage and observed that patients precociously treated with EPO showed a slower
      progression of renal failure. EPO has been demonstrated to have proliferative and
      anti-apoptotic effects in ischemia-reperfusion models in the brain and cell
      cultures. Moreover, EPO can mobilize stem cells and increase the plasmatic levels
      and the renal expression of VEGF. These effects seem to be dose-dependent and
      could be due to the activation of signal transduction systems, like Jak and STAT.
      In the presence of high doses of exogenous EPO or during the treatment with long
      acting EPO-like molecules, non-specific receptors may be activated through a low
      affinity link. Further investigations are needed to determine new therapeutic
      applications for EPO and other analogous hormones. Very long-acting molecules or
      molecules with cyto-protective but no erythropoietic effect may represent useful
      tools in the study of the molecular mechanisms underlying EPO's action and may
      have a rapid and safe therapeutic application.

PMID- 17497458
TI  - What is the best definition of contrast-induced nephropathy?
AB  - Radiological procedures require the intravascular administration of iodinated
      contrast media, which are becoming a great source of an iatrogenic disease known
      as contrast-induced nephropathy. The development of contrast-induced nephropathy
      is associated with prolonged hospitalization, the potential need for renal
      replacement therapy, and increased mortality. Despite numerous clinical and
      experimental studies, several important issues regarding contrast-induced
      nephropathy remain controversial. One of the controversial points is its very
      definition: a universally accepted definition of contrast-induced nephropathy
      does not exist. This can be a major problem. Differing definitions of contrast
      induced nephropathy and the clinical importance of these definitions were
      discussed in this letter.

PMID- 17497459
TI  - Effects of Ficus thonningii (Blume) [Morarceae] stem-bark ethanolic extract on
      blood glucose, cardiovascular and kidney functions of rats, and on kidney cell
      lines of the proximal (LLC-PK1) and distal tubules (MDBK).
AB  - Previous observations indicate that Ficus thonningii (Blume) [Moraceae] stem-bark
      extracts may be useful in the control of diabetes mellitus. Accordingly, we
      investigated in some experimental animal paradigms the effects of F. thonningii
      stem-bark ethanolic extract (FTE) on renal and cardiovascular functions as
      complications of diabetes. Oral glucose tolerance tests were conducted in
      separate groups of non-diabetic and STZ-treated diabetic rats given glucose load
      (0.86 g x kg(-1), p.o.) after 18-h fast, followed by various FTE doses (60, 120,
      and 240 mg x kg(-1)). Rats treated with deionized water (3 mL x kg(-1) p.o.), or
      metformin (500 mg x kg(-1) p.o.) acted as untreated and treated positive
      controls, respectively. Blood glucose was monitored at 15-min intervals for the
      first hour, and hourly thereafter for 3 h. Acute effects of FTE on kidney
      function and mean arterial blood pressure (MAP) were investigated in
      anaesthetized rats challenged with hypotonic saline after a 3.5-h equilibration
      for 4 h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. FTE was
      added to the infusate during the treatment period. Chronic effects of FTE were
      studied in individually caged rats treated daily with FTE (120 mg x kg(-1), p.o.)
      for five weeks. Cytotoxicity of FTE was assessed by dye-reduction colorimetric
      (MTT) assay on MDBK and LLCPK1 kidney cell lines exposed for 24 h, 48 h, and 72 h
      to graded concentrations of the extract. Myocardial contractile performance was
      evaluated on rat isolated atrial muscle strips. FTE, like metformin, decreased
      blood glucose levels in non-diabetic and STZ-diabetic rats. Both acute and
      chronic FTE treatments did not affect renal function. In vitro studies
      demonstrated that FTE increased MDBK cell metabolic activity by an average of 15%
      (72 h), and LLCPK1 mirrored the controls. Acute intravenous infusion of FTE
      reduced the MAP from 119 +/- 1 mmHg to 98 +/- 4 mmHg. The MAP also was reduced
      throughout the five-week experimental study period. FTE also produced
      concentration-dependent, negative inotropic and chronotropic effects on rat
      isolated, electrically driven left-, and spontaneously beating right-, atrial
      muscle preparations. Our experimental findings suggest that FTE possesses reno-
      and cardio-protective effects in diabetes mellitus.

PMID- 17497460
TI  - Furosemide prevents apoptosis and associated gene expression in a rat model of
      surgical ischemic acute renal failure.
AB  - Recently, we demonstrated that furosemide improves renal hemodynamics and
      attenuates ischemia/reperfusion (I/R)-associated changes in angiogenesis-related
      gene expression. However, the effect of furosemide on I/R-induced apoptosis is
      not known. We utilized a rat model of acute ischemic nephropathy to test the
      hypothesis that furosemide attenuates I/R-induced apoptosis. Male Sprague-Dawley
      rats anesthetized with urethane (50 mg/kg) were randomly allocated into four
      groups (n = 6 each): sham operated saline infusion, sham operated with furosemide
      (30 microg/kg/hr) infusion, unilateral renal ischemia (1 hr) followed by six
      hours of reperfusion, and I/R with furosemide infusion. Apoptosis was measured in
      kidney samples and compared between groups using ANOVA with Bonferroni
      correction. Apoptosis-related gene expression was assessed using microarray
      analysis and validated with RT-PCR. Phosphorylation of Akt was analyzed using
      ELISA, and data were compared between groups using the Mann Whitney U test.
      Compared to the control group, I/R significantly (p < 0.001) induced apoptosis in
      both the cortex and medulla. Similarly, microarray analysis revealed that I/R
      induced (< or = two-fold increase compared to control group) 73 apoptosis-related
      genes. Phosphorylation of Akt was significantly (p < 0.05) downregulated after
      I/R. Treatment with furosemide significantly (p < 0.001) reduced I/R-induced
      apoptosis in both the cortex and medulla and attenuated the expression of 72 I/R
      induced apoptosis-related genes. Compared to the I/R group, furosemide
      significantly (p < 0.01) upregulated the phosphorylation of Akt. These data
      suggest that a low dose furosemide infusion may attenuate I/R-induced apoptosis
      and associated gene transcription, and imply a possible novel molecular basis for
      the mechanism of action of furosemide in acute renal failure.

PMID- 17497461
TI  - Oxidized LDL accumulation in experimental renal ischemia reperfusion injury
      model.
AB  - BACKGROUND/AIMS: The aim of this study was to identify oxidative damage of kidney
      during ischemia reperfusion injury (IRI) by evaluating changes in lipid
      peroxidation markers in tissue and blood by an experimental model. Oxidized LDL
      (ox-LDL) was used as an oxidative stress biomarker, whereas paraoxonase (PON-1)
      activity was used as an antioxidative biomarker. METHODS: Sixty-three male Wistar
      rats were randomly assigned into three groups: renal IRI, sham, and control. In
      the renal IRI group, the right kidney was removed and the artery and vein of the
      left kidney were clamped for 90 minutes. The presence of ox-LDL in the kidney
      tissue sections was determined by using an immunofluorescent staining method.
      RESULTS: The plasma ox-LDL levels did not increase significantly at the 24th hour
      following IRI, made a peak at the 48th hour, and declined at the 72nd hour.
      Accumulation of ox-LDL was detected in the kidney tissue on the 24th, 48th, and
      72nd hours of the renal IRI. Serum PON-1 levels have peaked on the 24th hour and
      then declined. CONCLUSION: This study demonstrates the accumulation of ox-LDL
      molecules in the renal tissues of the IRI model. Future strategies aimed to
      reduce the lipid peroxidation during the initial hours of renal IRI may be useful
      to prevent complications of ischemia.

PMID- 17497462
TI  - Low plasma dehydroepiandrosterone sulfate level and its relationship to
      adiponectin in hemodialysis patients.
AB  - The aim of the present study was to assess the relationship between plasma DHEA-S
      and adiponectin concentrations in hemodialyses patients (HD). Plasma adiponectin,
      DHEA-S, cholesterol, and albumin levels were estimated in 94 HD and 46 healthy
      subjects (HS). In HD, a significantly lower plasma DHEA-S concentration (2.5+/
      0.2 vs. 4.7+/-0.4 micromol/L respectively; p = 0.002) but significantly higher
      plasma adiponectin level (15.0+/-0.7 vs. 8.7+/-0.8 microg/mL respectively; p =
      0.004) than in HS were found. Only in uremic patients was a significant negative
      correlation found between plasma adiponectin and DHEA-S concentrations (tau = 
      0.210; p = 0.001). Decreased plasma DHEA-S level is associated with increased
      adiponectinemia in uremic patients.

PMID- 17497464
TI  - Salt and fluid intake in the development of hypertension in peritoneal dialysis
      patients.
AB  - BACKGROUND: Although fluid overload contributes to hypertension in CAPD patients,
      less attention has been paid to the role of excess salt and fluid intake.
      Therefore, we investigated the role of salt and fluid intake in the development
      of hypertension in CAPD patients. METHODS: A total of 165 stable CAPD patients
      were included into this study. Based on the blood pressure in three consecutive
      months, they were divided into three groups: persistent hypertensive (PH; n =
      33), intercurrent hypertensive (IH; n = 58) and persistent normotensive (PN; n =
      74). The IH group was further divided into two phases: normotensive and
      hypertensive. Fluid status was evaluated by clinical assessment and bioimpedance
      analysis (BIA). RESULTS: There were no differences in age, gender, and duration
      of dialysis among groups. Patients were more fluid overloaded in the PH group.
      Extracellular water (ECW), total body water (TBW), and normalized extracellular
      water by height (NECW) were higher in the PH group than the PN group (16.77 +/-
      3.62 L vs. 14.61 +/- 2.92 L for ECW, p < 0.01; 32.22 +/- 8.23 L vs. 28.98 +/-
      6.00 L for TBW, p < 0.05; and 10.28 +/- 1.86 L/m vs. 9.08 +/- 1.63 L/m for NECW,
      p < 0.01). However, patients in the PH group also had more total fluid removal
      (TFR) and total sodium removal (TSR) compared with the PN group (1346.82 +/-
      431.27 mL/d vs. 1139.28 +/- 412.65 mL/d for TFR, p < 0.05; and 141.52 +/- 61.57
      mmol/d vs. 102.42 +/- 62.51 mmol/d for TSR, p < 0.01). The same trend was
      demonstrated when compared values of hypertensive and normotensive phase in IH
      group; patients had higher ECW, TBW, NECW, TSR, and PNa when they were in
      hypertensive phase than in the normotensive phase. CONCLUSIONS: This study
      confirmed that fluid overload was closely associated with the development of
      hypertension in CAPD patients. It also showed that hypertensive patients were in
      general more fluid overloaded despite a higher fluid and sodium removal as
      compared with normotensive patients.

PMID- 17497463
TI  - Is there a difference between the allergic potencies of the iron sucrose and low
      molecular weight iron dextran?
AB  - BACKGROUND: The objectives of the present trial were to compare the side effects
      and safety of two intravenous iron preparations (iron-dextran, iron-sucrose) in
      patients with end stage renal disease. METHODS: A total of 60 patients were
      randomized and assigned to one of two treatment groups (iron-dextran, n = 30;
      iron-sucrose, n = 30). A standard test dose of 25 mg of low molecular weight iron
      dextran and iron-sucrose were administered over 15 minutes during the initial
      visit, monitoring very closely for adverse reactions. If this dose was well
      tolerated, 75 mg of iron diluted in 100 mL of normal saline was administered over
      30 minutes. Adverse reactions were recorded. RESULTS: The mean age of the
      patients was 51.5+/-17.4 years (range, 21 to 80 years). Of the 30 patients who
      received low molecular weight iron-dextran, 11 developed side effects (pruritus,
      1 patient; wheezing, 1 patient; chest pain, 1 patient; nausea, 4 patients;
      hypotension, 1 patient; swelling, 1 patient; headache, 2 patients). Of the 30
      patients who received iron-sucrose, 13 developed side effects (pruritus, 1
      patient; wheezing, 1 patient; diarrhea, 1 patient; nausea, 4 patients;
      hypotension, 2 patients; swelling, 1 patient; headache, 3 patients). Adverse
      events occurred with similar frequency in the two treatment groups in our study
      (p > 0.05). We did not observe any serious reactions in the two groups.
      CONCLUSION: We conclude that the incidence of side effects associated with iron
      dextran was not different than that of iron-sucrose in our study. Large scale
      randomized studies are needed to compare the full side effect profile of
      intravenous iron preparations more precisely.

PMID- 17497465
TI  - Paraoxonase activity in glomerulonephritic patients.
AB  - BACKGROUND: Cardiovascular disease is the most common cause of morbidity and
      mortality in patients with chronic renal failure. Glomerulonephritic patients
      have an increased risk for cardiovascular disease, but its etiology is unclear.
      It is known that an increase in oxidizability of apolipoprotein B-containing
      lipoproteins has a key role in the initiation of atherosclerosis, and paraoxonase
      enzyme activity particularly has a preventive role against atherosclerosis. The
      aim of the present study was to evaluate the oxidizability of apolipoprotein B
      containing lipoproteins, serum, and urinary paraoxonase/arylesterase activities
      in glomerulonephritis patients who had normal lipid parameters and creatinine
      levels. METHODS: Thirty-two patients with glomerulonephritis and 22 healthy
      controls were included in this study. A total of 32 patients (including nine with
      membranous GN, eight with immunoglobulin A nephropathy, eight with mesangial
      proliferative GN, five with focal-segmental glomerulosclerosis, one with diffuse
      proliferative GN, and one with minimal chance disease having biopsy proven GN)
      were enrolled into the study. We compared serum and urinary paraoxonase,
      arylesterase, serum lipids, urea, creatinine, hemoglobin, total protein and
      albumin values between groups. RESULTS: Serum urea, creatinine, total protein,
      albumin, uric acid, hemoglobin, and lipid parameters were similar in the
      glomerulonephritis and control groups (p > 0.05). PON1 activity was significantly
      lower in GN group than controls, but there was no statistically significant
      difference on arylesterase activity between groups. Oxidizability of
      apolipoprotein B-containing lipoproteins was significantly higher in GN group
      than controls. CONCLUSION: Our study shows that the findings of normal serum
      levels of creatinine, lipids, and proteins increased the oxidizability of
      apolipoprotein B-containing lipoproteins, and any decrease in PON1 activity in
      patients diagnosed with GN should be considered important. Hence, the immediate
      commencement of preventive as well as curative treatment in other to avoid the
      risk of cardiovascular and renal problems would be a correct approach.

PMID- 17497466
TI  - Prednisolone co-administered with losartan confers renoprotection in patients
      with IgA nephropathy.
AB  - BACKGROUND: Treatment options for progressive IgA nephropathy are limited.
      METHODS: We performed a small, randomized controlled trial to evaluate the
      effects of prednisolone (PSL, 30 mg/dL, gradually tapered to 5 mg/dL over two
      years) plus 50 mg/day of losartan (LST, an angiotensin II receptor blocker) or
      PSL alone on IgA nephropathy. We separated 38 patients (age, 33 +/- 11 years;
      creatinine clearance, 103 +/- 31 mL/min; proteinuria, 1.6 +/- 0.5 g/day) into two
      groups that were treated with either PSL plus LST or PSL alone, and compared the
      proteinuria and creatinine clearance after two years. Baseline and
      histopathological data did not significantly differ between the two groups.
      RESULTS: Two years of treatment in both groups significantly decreased
      proteinuria compared with baseline, and PSL plus LST (from 1.6 +/- 0.6 to 0.3 +/-
      0.1 g/day, p < 0.05) was more effective than PSL alone (from 1.6 +/- 0.3 to 0.5
      +/- 0.1 g/day, p < 0.05). Creatinine clearance in both groups was similar at the
      start of study but significantly differed at the end of the study (PSL plus LST,
      104.3 +/- 36.4 to 100.4 +/- 38.9 mL/min; PSL alone, 103.4 +/- 28.5 to 84.8 +/-
      34.3 mL/min, p < 0.05). CONCLUSIONS: Combined therapy with PSL plus LST appears
      to be more effective than PSL alone in reducing proteinuria and protecting renal
      function in patients with IgA nephropathy.

PMID- 17497467
TI  - Effect of hemodialysis on the content of fatty acids in monolayers of erythrocyte
      membranes in patients with chronic renal failure.
AB  - Lipid metabolism disorders are found in patients with chronic renal failure
      (CRF). Changes in the content of fatty acids of the phospholipid fraction of
      erythrocyte membranes can lead to changes in the rheological properties. The
      objective of our study was to assess the effect of hemodialysis on the
      composition of fatty acids in two fractions of phospholipids: sphingomyelin (SPH,
      representative of the external monolayer) and phosphatidylethanolamine (PE,
      representative of the internal monolayer). Venous blood was drawn from patient
      with CRF before and after the HD procedure. Lipids from the erythrocyte stroma
      were extracted using the Rose and Oklander method and then were separated into
      phospholipid fractions using thin-layer chromatography (TLC). PE and SPH
      fractions were extracted, and the fatty acid profile was determined using gas
      chromatography (Perkin Elmer 8400; RTx 2330 column; length: 105 m). In the
      phospholipid fractions tested, a high content of saturated FA with a medium
      carbon chain (C 16:0 to C 18:2) and a long carbon chain such as C 24:0, C 24:1; C
      22:6; and C 26:0 was found. The HD procedure affected the FA profile in the
      fractions tested. The proportion of saturated and unsaturated long-chain FA
      (above 18 C) increased in PE. However, the content of medium-chain FA C 16:0 to C
      18:1 decreased. A significant decrease in the content of the majority of long
      chain FA could be noted in SPH. The ratio of unsaturated (U) to saturated (S)
      fatty acids in the SPH fraction increased. Hemodialysis has a significant effect
      on the content of fatty acids in the PE and SPH fractions of erythrocyte
      membranes in patients with CRF.

PMID- 17497468
TI  - Higher incidence of cholelithiasis in chronic renal failure patients with
      secondary hyperparathyroidism undergoing peritoneal dialysis.
AB  - BACKGROUND: In this study, we endeavored to determine whether the incidence of
      cholelithiasis (CL) was increased in chronic renal failure (CRF) patients with
      secondary hyperparathyroidism on a peritoneal dialysis (PD) program. We also
      evaluated the factors that might have some influence on the development of CL.
      METHODS: A total of 59 CRF patients undergoing PD were included in the study. We
      studied the following groups to determine whether parathyroid hormone (PTH)
      levels were increased in CRF-PD patients: twenty patients with secondary
      hyperparathyroidism (group 1) and 39 patients with normal PTH levels (group 2).
      PTH levels were maintained at three times the upper limit of normal. Biochemical
      parameters were obtained for each CRF-PD patient. All patients underwent
      abdominal ultrasonography to screen for the presence of cholelithiasis. For
      statistical analysis, chi2, t test, and logistic regression analysis were used; p
      < 0.05 was considered as significant. RESULTS: We found an almost ten times
      higher incidence (25% vs. 2.6%) of CL in group 1 patients with statistical
      significance (p = 0.007). When the incidence of CL according to sex, creatinine,
      and PTH levels were considered, female gender, creatinine, and PTH levels were
      higher in group 1, which was also significant statistically. No significant
      relationship was detected between gallbladder stone formation and the other
      analyzed biochemical parameters. CONCLUSIONS: We found that the incidence of CL
      in CRF-PD patients with secondary hyperparathyroidism was higher than CRF-PD
      patients with normal PTH levels. It was also detected that female gender, high
      creatinine levels, and elevated PTH levels might influence the development of CL
      in CRF-PD patients.

PMID- 17497469
TI  - Human immunodeficiency virus (HIV) infection screening in a dialysis unit.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) screening is a routine for long
      term hemodialysis patients because of a high risk for infection. Enzyme
      immunoassay (EIA) is a simple tool for screening HIV, but clinically false
      positive EIA is a frequent result. Other tests such as Western blot analysis (WB)
      and HIV DNA and RNA by polymerase chain reaction have better specificity and
      sensitivity, but they cannot be accessible in many dialysis units. METHODS: Four
      hundred and four patients with end stage renal disease on long-term hemodialysis
      were screened with EIA for HIV antibodies. Repeated EIA was performed if the
      first test was positive result. WB was used as the confirmatory test. RESULTS:
      Two persons initially showed a positive EIA pattern among the 404 patients, but
      nobody had positive WB test result later. CONCLUSION: The ratio of false-positive
      EIA results for screening HIV is relatively high in long-term hemodialysis
      patients. Further tests should be employed to confirm the diagnosis.

PMID- 17497470
TI  - Predictors of mortality in acute renal failure in a developing country: a
      prospective study.
AB  - Acute renal failure (ARF) occurs in wide range of conditions, making the
      evaluation of its prognosis a difficult task. Data regarding prognostic factors
      in ARF in a general population in developing countries are scarce. The objective
      of the study was to describe predictors of mortality in ARF that are relevant in
      the developing world. This prospective study was carried out over a one-year
      period; all hospitalized adults with ARF were included in the study. Predictors
      of mortality studied included causes of ARF, pre-existing diseases, and severity
      as well as complications of ARF. Of 33,301 patients admitted during the study
      period, 294 (0.88%) were either admitted with or developed ARF after
      hospitalization. Mean age was 43.9 +/- 16.9 (18-86 yrs). Sepsis was the most
      common cause (63.26%). Pre-existing diseases like cardiovascular disease (CVSD),
      respiratory system disease (RSD), central nervous system disease (CNSD),
      hypertension, diabetes mellitus (DM), and malignancy were significantly higher in
      elderly as compared to younger patients. On univariate analysis sepsis,
      hypoperfusion as a cause of ARF and hospital-acquired ARF were associated with
      higher mortality. Pre-existing diseases viz. RSD, CVSD, CNSD, and DM had higher
      mortality. Among the severity and complications of ARF, oliguria, bleeding and
      infection during the course of ARF and critical illness were predictors of poor
      outcome. Age > 60 yrs was associated with significantly higher mortality.
      However, on multivariate analysis, only critical illness (odds ratio 37.3), age >
      60 years (odds ratio of 5.6), and sepsis as cause of ARF (odds ratio of 2.6) were
      found to be independent predictors of mortality.

PMID- 17497471
TI  - The effect of alendronate, risedronate, and raloxifene on renal functions, based
      on the Cockcroft and Gault method, in postmenopausal women.
AB  - BACKGROUND: Oral alendronate, risedronate, and raloxifene are effective treatment
      options in the management of postmenopausal osteoporosis. There is little
      previously reported about the renal safety profiles of these three agents in
      osteoporosis. We aimed to assess the risk of renal toxicity associated with oral
      alendronate, risedronate, and raloxifene in the treatment of osteoporosis,
      prospectively. METHODS: One hundred and twenty-seven patients with osteoporosis
      and osteopenia according to lumbar or femoral-neck bone mineral density t score
      were enrolled in the study. The patients were randomized to alendronate 70 mg
      once weekly (n = 47), risedronate 35 mg once weekly (n = 44), or raloxifene 60 mg
      per day (n = 36) for one year. Preliminary screening included medical history,
      physical examination, lumbar and femoral bone mineral densitometry measurement,
      and blood biochemical tests, including renal function tests. The biochemical
      markers were then assessed at the end of 12 months. RESULTS: There was no
      significant difference between basal and final renal function parameters of each
      group. Also these parameters did not differ between the three groups after 12
      months of treatment period. CONCLUSIONS: These results demonstrate that
      alendronate, risedronate, and raloxifene are all safe drugs for renal functions
      in the treatment of osteoporosis.

PMID- 17497472
TI  - Evaluation of hand functions in hemodialysis patients.
AB  - BACKGROUND AND AIMS: Patients with end stage renal disease (ESRD) have many
      musculoskeletal abnormalities, including hand dysfunction. The Sollerman test
      evaluates hand grip function in daily activities. The relationships between
      Sollerman test (dominant hand) with Duruoz's Hand Index (DHI), Health Assessment
      Questionnaire (HAQ), and Beck Depression Inventory (BDI) tests have not been
      investigated previously. The aims of this study are to evaluate hand grip
      function using the Sollerman test in hemodialysis (HD) patients, correlate this
      test with other measures evaluating hand function or psychosocial status, and
      investigate factors that can affect Sollerman test. METHODS: One-hundred twenty
      HD patients (64 male, 56 female, mean age 51 +/- 1.4 years, mean duration of HD
      therapy 5.3 +/- 3.7 years) were included in this study. The HAQ, DHI, and BDI
      scores were determined by standard techniques. All patients underwent the Jamar
      grip test and Sollerman test for the dominant (D) and non-dominant hand (ND).
      RESULTS: We found a positive correlation between Sollerman test (dominant hand)
      with Sollerman test-ND, Jamar-D, and Jamar-ND tests. There were negative
      correlations between Sollerman test with age, HAQ, BDI, and DHI tests.
      CONCLUSIONS: The relationships between Sollerman test (dominant hand) with DHI,
      HAQ, and BDI tests have not been investigated previously. This study showed the
      correlations between the Sollerman test (dominant hand) and other tests (either
      positive or negative). Psychosocial problems can affect hand functions.

PMID- 17497473
TI  - Ultrasonographic maturation of native arteriovenous fistulae: a follow-up study.
AB  - BACKGROUND/AIMS: Ideal time needed for arteriovenous fistula (AVF) maturation is
      still controversial. In this study, we aimed to investigate the natural course of
      AVF maturation and also investigated the factors affecting AVF maturation.
      METHODS: We studied 31 (21M/10F, mean age 55.8 +/- 16.2) chronic renal failure
      patients. We evaluated the patients with color Doppler ultrasound examination
      before the fistula operation, at the first day, and at the first, second, third,
      and sixth months. Radial artery (RA) diameter, flow velocity, flow, resistance
      index, fistula vein diameter, flow velocity, and flow were measured. RESULTS:
      Patency rates at the first post-operative day and the sixth month were 87.1% and
      67.1%, respectively. Cephalic vein flow was 451.2 +/- 248.6 mL/min at the first
      month and 528.6 +/- 316.5 mL/min at the sixth month. Baseline RA diameter was
      lower in failing fistulas than that of patent fistulas. Failing fistulas were
      more common in women. CONCLUSION: Blood flow was enough for hemodialysis at the
      end of the first month. However, fistula maturation had continued until the end
      of the study; women and patients with low RA diameter are particularly prone to
      fistula failure. Therefore, especially in these patients, AVF must be created at
      least three or four months before the predicted hemodialysis initiation time.

PMID- 17497474
TI  - Increased body mass index is not a reliable marker of good nutrition in
      hemodialysis patients.
AB  - OBJECTIVE: The aim of the study was to assess the body fat (BF) composition in
      hemodialysis (HD) patients using anthropometry and bioelectrical impedance
      analysis (BIA) and investigate relationships between BIA-determined BF
      composition and nutritional parameters in different weight groupings. DESIGN:
      Cross-sectional study. SETTING: A tertiary-care university hospital. METHODS: 164
      HD patients (M/F: 89/75, mean age: 48.4 +/- 15.8 years, mean HD duration: 58.2 +/
      42.6 months) were divided into three groups according to body mass index (BMI):
      normal weight (NW: BMI 18.5-24.9), overweight (OW: BMI 25-29.9), obese (OB, BMI >
      or = 30). Biochemical parameters and BF composition using anthropometry and foot
      to-foot BIA were compared between three groups. RESULTS: Ninety-six (59%)
      patients were NW, 40 (24%) were OW, and 28 (17%) were OB. Average mean skinfold
      thickness (p = 0.005), mid-arm circumference (p = 0.001), BF% (p = 0.001), and
      fat-free mass (FFM) (p = 0.03) were all significantly greater in the OB group
      than in the NW group. Compared to the NW patients, the OB group had significantly
      higher serum levels of glucose (p = 0.03), total cholesterol (p = 0.02), and
      triglycerides (p = 0.02), but significantly lower serum albumin (p = 0.05) and
      blood urea nitrogen (p = 0.05). The OB group also had significantly higher white
      blood cell count (p = 0.002) and serum CRP (p = 0.001) than the NW group.
      CONCLUSIONS: The results suggest that BIA-determined BF composition is correlated
      with body mass index. In addition, obesity is associated with elevated CRP and
      white blood cell count and lower serum albumin level in HD patients.

PMID- 17497475
TI  - Effect of hyperbaric oxygen on cyclosporine-induced nephrotoxicity and oxidative
      stress in rats.
AB  - Reactive oxygen species have been suggested to be involved in cyclosporine
      nephrotoxicity. Hyperbaric oxygen is known to induce the generation of reactive
      oxygen species in tissues. The aim of this study was to investigate whether the
      use of hyperbaric oxygen concurrently with cyclosporine potentiates cyclosporine
      nephrotoxicity by inducing oxidative stress in kidneys. The study consisted of
      four groups of rats: a control group, a cyclosporine group (15 mg/kg/day
      intraperitoneally for 14 days), a hyperbaric oxygen group (60 min. every day for
      five days at 2.5 atmosphere absolute), and a cyclosporine + hyperbaric oxygen
      group (cyclosporine 15 mg/kg/day intraperitoneally for 14 days + hyperbaric
      oxygen for 60 min at 2.5 atmosphere absolute every day for five days on the last
      five days of cyclosporine treatment). Oxidative stress was determined by
      measuring renal thiobarbituric acid-reactive substances content, renal superoxide
      dismutase, and glutathione peroxidase activities. Cyclosporine increased serum
      urea and creatinine levels, indicating the development of nephrotoxicity, and
      induced significant oxidative stress in rat kidneys. Hyperbaric oxygen alone did
      not alter any of the biochemical and oxidative stress parameters compared to the
      control group. When used concurrently with cyclosporine, hyperbaric oxygen
      significantly reduced cyclosporine-induced oxidative stress, but it neither
      attenuated nor aggravated cyclosporine-induced nephrotoxicity. These results
      suggest that reactive oxygen species are involved in cyclosporine nephrotoxicity,
      but are not the direct cause of the toxicity. Although concurrent use of
      cyclosporine and hyperbaric oxygen did not exacerbate cyclosporine nephrotoxicity
      in this model, we recommend that the renal functions of patients be monitored
      periodically when these treatments are used concurrently.

PMID- 17497476
TI  - The evaluation of effects of demographic features, biochemical parameters, and
      cytokines on clinical outcomes in patients with acute renal failure.
AB  - AIM: To evaluate the effects of cytokines, biochemical parameters and demographic
      features on clinical outcomes of acute renal failure (ARF). PATIENTS AND METHODS:
      59 patients with acute renal failure (28 men, 31 women) were enrolled to the
      study. Cytokines, biochemical parameters, and complete blood count were measured.
      Patients were divided into two groups: as survivors (group 1, n = 46) and
      nonsurvivors (group 2, n = 13). RESULTS: Mean age of patients were 52.3 +/- 17.9
      years. 46 patients survived (77.9%) and 13 patients died (22.1%). There was a
      statistically significant relationship between IL-2R, IL-6, and TNF-alpha levels
      and mortality rates (p = 0.004, p = 0.016, p = 0.020, respectively) and between
      TC levels and mortality rates (p = 0.041). In multivariable logistic regression
      analysis, the effects of proinflammatory cytokines (IL-1beta, IL-2R, IL-6,
      TNFalpha, CRP, and ESR) on the clinical outcomes in ARF was observed to be
      statistically significant (r = 0.341, p = 0.005). CONCLUSION: We realized that in
      totally demographic features (male gender, advanced age, poor nutritional
      status), biochemical parameters (TC, albumin, and hemoglobin) and cytokine levels
      (IL-2R, IL-6, TNF-alpha), CRP and ESR may be predictive factors for mortality in
      patients with ARF.

PMID- 17497477
TI  - Parathyroid hormone as a marker for the differential diagnosis of acute and
      chronic renal failure.
AB  - It is often difficult to distinguish acute renal failure clinically from chronic
      renal failure, especially in patients who do not have records of their medical
      history. We investigated the magnitude of iPTH increase in ARF and the potential
      role of iPTH as a marker for differential diagnosis of ARF and CRF in new
      patients referred to our renal unit. We prospectively analyzed 122 (ARF n = 64,
      CRF n = 58) patients referred to our renal unit with serum creatinine higher than
      2 mg/dL. ROC curve analysis was performed to investigate role of iPTH for
      differentiating ARF from CRF. The sensitivity, specificity, and positive
      predictive value of iPTH in discrimination of ARF and CRF were calculated. There
      was no statistically significant difference regarding the means of age, sex
      distribution, and serum chemistry between patients with ARF or CRF. But serum
      iPTH (p < 0.0001) levels were lower in patients with ARF than in those with CRF.
      A cutoff, set at 170 pg/mL for iPTH to discriminate patients with CRF, yielded a
      sensitivity of 88% and a specificity of 89%. This study confirms that the iPTH
      measurement is of clinical value in differentiating acute from chronic renal
      failure.

PMID- 17497478
TI  - Hypercalcemia and suppressed PTH levels in a renal transplant patient infected
      with Pneumocystis carinii.
AB  - Pneumocystis carinii pneumonia is a serious and relatively common complication of
      immunosuppressive therapy. In immunocompromised patients, P. carinii pneumonia
      can cause significant morbidity and mortality. Another common complication,
      typically seen in the subpopulation of renal transplant recipients, is
      hypercalcemia. The prevalence of hypercalcemia varies, reaching as high as 71%.
      We report the case of a renal transplant recipient who developed P. carinii
      pneumonia and hypercalcemia, the latter being resolved after the successful
      treatment of the former. We argue that there is a causal relationship between P.
      carinii pneumonia and hypercalcemia in renal transplant recipients. In
      immunocompromised patients, pulmonary infection accompanied by hypercalcemia
      should raise the suspicion of P. carinii pneumonia.

PMID- 17497479
TI  - Two cases with horseshoe kidney in association with nephrotic syndrome: is there
      a causal relationship between two conditions?

PMID- 17497481
TI  - New organization of general practice in Norway from 1 January 2007.

PMID- 17497482
TI  - Avoiding humiliations in the clinical encounter.
AB  - OBJECTIVES: To explore potentials for avoiding humiliations in clinical
      encounters, especially those that are unintended and unrecognized by the doctor.
      Furthermore, to examine theoretical foundations of degrading behaviour and
      identify some concepts that can be used to understand such behaviour in the
      cultural context of medicine. Finally, these concepts are used to build a model
      for the clinician in order to prevent humiliation of the patient. THEORETICAL
      FRAME OF REFERENCE: Empirical studies document experiences of humiliation among
      patients when they see their doctor. Philosophical and sociological analysis can
      be used to explain the dynamics of unintended degrading behaviour between human
      beings. Skjervheim, Vetlesen, and Bauman have identified the role of objectivism,
      distantiation, and indifference in the dynamics of evil acts, pointing to the
      rules of the cultural system, rather than accusing the individual of bad
      behaviour. Examining the professional role of the doctor, parallel traits
      embedded in the medical culture are demonstrated. According to Vetlesen,
      emotional awareness is necessary for moral perception, which again is necessary
      for moral performance. CONCLUSION: A better balance between emotions and
      rationality is needed to avoid humiliations in the clinical encounter. The
      Awareness Model is presented as a strategy for clinical practice and education,
      emphasizing the role of the doctor's own emotions. Potentials and pitfalls are
      discussed.

PMID- 17497483
TI  - "A memorable consultation": writing reflective accounts articulates students'
      learning in general practice.
AB  - OBJECTIVES: To explore and analyse students' learning experiences of a memorable
      consultation during a final-year attachment in general practice. SETTING: After a
      two-week primary care attachment in the undergraduate curriculum, students were
      invited to write a reflective account of a memorable consultation. DESIGN: A
      total of 52 reflective accounts were read and processed according to qualitative
      content analysis. Credibility of the analysis was validated by two co-authors
      reading the descriptions separately and trustworthiness was tested at local
      seminars. RESULTS: Three main themes emerged. In "The person beyond symptoms" the
      students recognize the individual properties of a consultation. "Facing
      complexity" mirrors awareness of changing tracks in problem-solving and
      strategies of handling unclear conditions. "In search of a professional role"
      reflects the interest in role modelling and the relation to the supervisor.
      CONCLUSION: Involving students in writing reflective accounts appears to
      stimulate them to articulate practice experiences of the consultation.

PMID- 17497484
TI  - Balancing - an equilibrium act between different positions: an exploratory study
      on general practitioners' comprehension of their professional role.
AB  - OBJECTIVE: There is a call to make the duties and working conditions of the GP
      more transparent. The aim of this study was to explore practising GPs' personal
      experiences of their professional role and what they regard to be its salient
      characteristics. DESIGN: An exploratory and descriptive study was undertaken by
      interviewing GPs and by performing a focus-group study of experienced GPs. The
      interviews were transcribed and analysed, and the text was categorized according
      to content analysis. SETTING: The practice of the interviewed GPs. SUBJECTS:
      Seven GPs in individual interviews and a focus group of experienced GPs. RESULTS:
      A major theme, Balancing, was identified. It was derived from a number of
      opposing concepts to which different features were related. "The good shepherd"
      versus "The medical expert"; "Curing" versus "Caring"; "Short visits" versus
      "Long consultations"; "The personal doctor" versus "The society's doctor". In
      many consultations the GP has to contemplate how to stay in focus between these
      diverse roles. CONCLUSION: General practice requires a balance to be achieved
      between a number of opposing conditions. In their clinical work GPs have to
      adjust to and integrate alternative perspectives. Problems of recruiting new GPs
      might be associated with dilemmas in this balancing act.

PMID- 17497485
TI  - The profiles of adults who consult alternative health practitioners and/or
      general practitioners.
AB  - OBJECTIVE: To compare the profiles of people visiting only a general practitioner
      (GP), those visiting only a practitioner of complementary and alternative
      medicine (CAM), and those visiting both (GP&CAM). DESIGN: A comparative total
      population health survey in central Norway (HUNT 2). SUBJECTS: A total of 54,448
      persons 20 years of age and over who answered questions about their use of health
      services during the previous 12 months. VARIABLES: Sociodemographic
      characteristics, self-perceived health, subjective health complaints, and a
      variety of common diseases. RESULTS: Some 34,854 (64.0%) of those who answered
      the health service use question had visited only a GP, 837 (1.5%) only a CAM
      practitioner, and 4563 (8.4%) both during the last 12 months. The likelihood of
      being a CAM-only user as compared to a GP-only user was significantly increased
      (p < 0.005) if the participant was male; aged between 30 and 69; and without
      cardiovascular disease. The likelihood of being a GP&CAM user compared with a GP
      only user was significantly increased (p < 0.005) for those who were female; aged
      between 30-59; had a higher education level; were non-smokers; had lower
      perceived global health; had a limiting chronic complaint; had experienced a
      health complaint during the last 12 months; had musculoskeletal disease; had a
      psychiatric complaint; and had hay fever. CONCLUSION: There were few CAM-only
      users and they differ from GP-only users by being male, aged 30-69, and without
      cardiovascular disease. Users of both GP&CAM were less healthy with more
      complaints and poorer self-reported health than GP- and CAM-only users.

PMID- 17497486
TI  - Promotional methods used by representatives of drug companies: a prospective
      survey in general practice.
AB  - OBJECTIVE: To examine the extent and composition of pharmaceutical industry
      representatives' marketing techniques with a particular focus on drug sampling in
      relation to drug age. DESIGN: A group of 47 GPs prospectively collected data on
      drug promotional activities during a six-month period, and a sub-sample of 10 GPs
      furthermore recorded the representatives' marketing techniques in detail.
      SETTING: Primary healthcare. SUBJECTS: General practitioners in the County of
      Funen, Denmark. MAIN OUTCOME MEASURES: Promotional visits and corresponding
      marketing techniques. RESULTS: The 47 GPs recorded 1050 visits corresponding to a
      median of 19 (range 3 to 63) per GP in the six months. The majority of drugs
      promoted (52%) were marketed more than five years ago. There was a statistically
      significant decline in the proportion of visits where drug samples were offered
      with drug age, but the decline was small OR 0.97 (95% CI 0.95;0.98) per year.
      Leaflets (68%), suggestions on how to improve therapy for a specific patient
      registered with the practice (53%), drug samples (48%), and gifts (36%) were the
      most frequently used marketing techniques. CONCLUSION: Drug-industry
      representatives use a variety of promotional methods. The tendency to hand out
      drug samples was statistically significantly associated with drug age, but the
      decline was small.

PMID- 17497487
TI  - GPs' thoughts on prescribing medication and evidence-based knowledge: the benefit
      aspect is a strong motivator. A descriptive focus group study.
AB  - OBJECTIVE: To describe GPs' thoughts of prescribing medication and evidence-based
      knowledge (EBM) concerning drug therapy. DESIGN: Tape-recorded focus-group
      interviews transcribed verbatim and analysed using qualitative methods. SETTING:
      GPs from the south-eastern part of Vastra Gotaland, Sweden. SUBJECTS: A total of
      16 GPs out of 178 from the south-eastern part of the region strategically chosen
      to represent urban and rural, male and female, long and short GP experience.
      METHODS: Transcripts were analysed using a descriptive qualitative method.
      RESULTS: The categories were: benefits, time and space, and expert knowledge. The
      benefit was a merge of positive elements, all aspects of the GPs' tasks. Time and
      space were limitations for GPs' tasks. EBM as a constituent of expert knowledge
      should be more customer adjusted to be able to be used in practice. Benefit was
      the most important category, existing in every decision-making situation for the
      GP. The core category was prompt and pragmatic benefit, which was the utmost
      benefit. CONCLUSION: GPs' thoughts on evidence-based medicine and prescribing
      medication were highly related to reflecting on benefit and results. The
      interviews indicated that prompt and pragmatic benefit is important for
      comprehending their thoughts.

PMID- 17497488
TI  - Which population groups should be targeted for cardiovascular prevention? A
      modelling study based on the Norwegian Hordaland Health Study (HUSK).
AB  - OBJECTIVE: To assess level of cardiovascular risk factors in a non-selected,
      middle-aged population. To estimate the proportion target for risk intervention
      according to present guidelines and according to different cut-off levels for two
      risk algorithms. DESIGN: Population survey, modelling study. SETTING: The
      Norwegian Hordaland Health Study (HUSK) 1997-99. SUBJECTS: A total of 22 289
      persons born in 1950-57. MAIN OUTCOME MEASURES: Own and relatives' cardiovascular
      morbidity, antihypertensive and lipid-lowering treatment, smoking, blood
      pressure, cholesterol. Framingham and Systematic Coronary Risk Evaluation (SCORE)
      algorithms. The European guidelines on CVD prevention in clinical practice were
      applied to estimate size of risk groups. RESULTS: Some 9.7% of men and 7.6% of
      women had CVD, diabetes mellitus, a high level of one specific risk factor, or
      received lipid-lowering or antihypertensive treatment. Applying a SCORE (60
      years) cut-off level at 5% to the rest of the population selected 52.4% of men
      and 0.8% of women into a primary prevention group, while a cut-off level at 8%
      included 22.0% and 0.06% respectively. A cut-off level for the Framingham score
      (60 years) of 20% selected 43.6% of men and 4.7% of women, while a cut-off level
      of 25% selected 25.6% of men and 1.8% of women. CONCLUSION: The findings
      illustrate how choices regarding risk estimation highly affect the size of the
      target population. Modelling studies are important when preparing guidelines, to
      address implications for resource allocation and risk of medicalization. The
      population share to be targeted for primary prevention ought to be estimated,
      including the impact of various cut-off points for risk algorithms on the size of
      the risk population.

PMID- 17497489
TI  - How do patients at risk portray candidates for coronary heart disease? A
      qualitative interview study.
AB  - OBJECTIVE: To explore how patients at risk of coronary heart disease (CHD)
      portray candidates for CHD. DESIGN: Qualitative interview study. SETTING: Norway.
      SUBJECTS: A total of 20 men and 20 women diagnosed with heterozygous familial
      hypercholesterolemia (FH) recruited through a lipid clinic. MAIN OUTCOME
      MEASURES: Participants' beliefs concerning persons who are considered candidates
      for CHD. RESULTS: Some participants believed that CHD could happen to anyone,
      while the majority conveyed detailed notions of persons they considered to be
      likely victims of CHD. Participants often portrayed the coronary candidate as
      someone who was different from themselves. Among those who mentioned gender, all
      presented the candidate as a man. Some women said that they had to reconcile
      themselves to being at risk of CHD, since they at first had conceived CHD as a
      man's disease. While some participants considered their notions to be valid for
      assessing people's risk of CHD, others questioned how valid their notions were.
      CONCLUSION: Doctors should recognize that distancing is a way patients cope with
      risk and that such a strategy may have psychological and moral reasons. When
      communicating about risk, doctors should take into account that patients' notions
      of risk may differ from medical notions of risk.

PMID- 17497490
TI  - Exercise testing and myocardial perfusion scintigraphy in primary care patients
      with chest pain of new onset.
AB  - OBJECTIVE: To analyse the outcome of exercise testing and myocardial perfusion
      scintigraphy (MPS) in primary care patients with chest pain of new onset. DESIGN:
      Prospective, observational. Patients aged 20-79 years, consulting due to chest
      pain of new onset, were enrolled consecutively. SETTING: Three primary care
      health centres in south-eastern Sweden. PATIENTS: 191 patients where the
      possibility of stable ischaemic heart disease (IHD) could not be excluded by
      clinical examination alone. MAIN OUTCOME MEASURES: Exercise test results, when
      equivocal completed by MPS. RESULTS: Exercise testing revealed IHD in 14 (7%) and
      no IHD in 134 (70%) of the cases. In 43 (23%) the exercise test results were
      equivocal. Thirty-nine of these patients underwent MPS, which showed IHD in 19
      and no IHD in 20 cases. Among previously diagnosed cardiovascular disease and
      risk factors only atrial fibrillation in the male group showed a significant
      correlation to the outcome IHD. CONCLUSION: Exercise testing and MPS are both
      useful when investigating chest pain patients in primary care.

PMID- 17497491
TI  - Bleeding complications during warfarin treatment in primary healthcare centres
      compared with anticoagulation clinics.
AB  - OBJECTIVES: To examine determinants of bleeding complications during warfarin
      treatment in an unselected patient population and evaluate possible differences
      in safety between specialized anticoagulation clinics and primary healthcare
      centres. DESIGN: Prospective cohort study. Data were collected with an admission
      form and medical records were scrutinized in order to pursue all adverse events.
      Differences between groups were estimated with a t-test and chi-squared test, and
      univariate and multivariate Cox regression analysis. SETTING: All patients
      treated and monitored with oral anticoagulation in primary healthcare centres and
      specialized anticoagulation clinics in the Sundsvall and Skelleftea region
      (northern Sweden) during a five-year period. SUBJECTS: A total of 2731 patients
      corresponding to 5044 treatment years. MAIN OUTCOME MEASURES: Bleedings were
      classified as fatal or major. Major bleedings were defined as an event causing
      admission, prolonged in-hospital care or death. RESULTS: In total 195 major
      bleedings occurred corresponding to 3.9% per treatment year, including 34 fatal
      events (0.67% per treatment year). Patients monitored at the two specialized
      anticoagulation clinics combined had a major bleeding frequency of 4.1% as
      compared with 3.9% at primary healthcare units. The frequency of fatal
      haemorrhage was 0.57% and 0.76%, respectively. The rate of major and fatal
      bleeding was age related with an increase of 4% and 5%, respectively, per year.
      CONCLUSIONS: There was no difference in bleeding complications between patients
      monitored at primary healthcare centres and specialized anticoagulation clinics.
      Age was continuously and independently associated with bleeding risk. These study
      data indicate the need to exercise caution in treatment of the elderly.

PMID- 17497492
TI  - Chimeras of nurture.

PMID- 17497493
TI  - Response to open peer commentaries on "Neuroethics and national security".

PMID- 17497494
TI  - Neuroethics and national security.

PMID- 17497495
TI  - Response to open peer commentaries on "Thinking about the human neuron mouse".

PMID- 17497496
TI  - Neuroethics, national security and secrecy.

PMID- 17497497
TI  - Neuroethics and human rights.

PMID- 17497498
TI  - Ethical intelligence from neuroscience: is it possible?

PMID- 17497499
TI  - Neuroscience and the free will conundrum.

PMID- 17497500
TI  - Against the use of medical technologies for military or national security
      interests.

PMID- 17497501
TI  - Total information awareness--forgotten but not gone: lessons for neuroethics.

PMID- 17497503
TI  - Part-human chimeras: worrying the facts, probing the ethics.

PMID- 17497502
TI  - Thinking about the human neuron mouse.

PMID- 17497504
TI  - Beyond the human neuron mouse to the NAS Guidelines.

PMID- 17497505
TI  - The moral musings of a murine chimera.

PMID- 17497506
TI  - Further thoughts about the human neuron mouse.

PMID- 17497507
TI  - Creating non-human persons: might it be worth the risk?

PMID- 17497508
TI  - Of mice and men.

PMID- 17497509
TI  - The ethical mouse: be not like Icarus.

PMID- 17497512
TI  - Alcohol involvement in fatal crashes under three crash exposure measures.
AB  - OBJECTIVE: A common method of normalizing crash fatality data for comparing
      subgroups of drivers has been the estimated vehicle miles traveled (VMT).
      Unfortunately, the VMT method fails to provide for exposure to risks such as
      those related to alcohol consumption (among others). Recently, the "crash
      incidence ratio" (CIR) has been introduced to address some of these limitations.
      The goals of this study are first, to show that the CIR method is intrinsically
      similar to an increasingly popular quasi-induced method: the relative accident
      involvement ratio (RAIR); second, to compare the VMT-based, the CIR, and the RAIR
      methods when applied to the evaluation of alcohol-related crash fatalities across
      racial/ethnic groups. METHODS: We use the 1990-1996 Fatal Accident Reporting
      System (FARS) with information on the drivers' race/ethnicity and alcohol
      involvement (BAC). Descriptive and statistical ratio tests were applied. RESULTS:
      The RAIR and CIR are indeed closely related measures that, when used for
      comparisons against a reference group, yield exactly the same numerical
      estimates. Strikingly different outcomes were obtained depending on using the VMT
      or the CIR/RAIR. CONCLUSION: Choosing one measure over another should depend on
      the questions to be answered. The implication of this finding for researchers and
      policy makers is discussed.

PMID- 17497513
TI  - The impact of visual perspective and anger on the actor-observer bias among
      automobile drivers.
AB  - OBJECTIVE: The present study was designed to examine the combined impact of the
      Actor-Observer Bias and driver anger on attributions of other drivers. METHODS:
      Participants watched a simulated driving sequence in which a car swerved in front
      of a truck in near collision. Half viewed from the perspective of the offending
      motorist while the other half viewed from the perspective of a trailing motorist.
      Participants then rated the general riskiness of the offending motorist and the
      responsibility of the victim driver. RESULTS: Findings support the visual
      perspective explanation of the Actor-Observer Bias in that attributions within a
      single event differed based on the random assignment of visual perspective.
      However, the nature of the attributions interacted with the level of anger
      experienced over the incident. Those viewing as a trailing motorist provided
      greater riskiness ratings for the offending motorist than did those viewing from
      the perspective of the offending motorist, but only when scoring/rating high on
      personal feelings of anger regarding the observed incident. CONCLUSION: The
      present study demonstrates that personal factors and common cognitive biases can
      influence how events in the traffic environment are perceived, and the subsequent
      judgments made of other drivers following negative events.

PMID- 17497514
TI  - Effectiveness and driver acceptance of the Honda belt reminder system.
AB  - OBJECTIVE: Prior research suggests that vehicle-based seat belt reminder systems
      can produce moderate increases in belt use rates. However, these findings were
      based on a limited set of Ford vehicles in one geographic location. As more
      vehicles with reminder systems enter the market, it is important to determine
      their effectiveness as well as acceptance by consumers. The present study
      investigated the effectiveness of Honda's belt reminder system. METHODS: Driver
      belt use was observed unobtrusively as drivers brought their Honda vehicles to
      dealerships for service. Drivers also were asked to complete a mail-in survey
      designed to elicit their experience with the system. RESULTS: Belt use was
      significantly higher among drivers of vehicles with belt reminders compared with
      drivers of vehicles without reminders (90 vs. 84 percent). Use rates in vehicles
      with reminders were higher among both male and female drivers and in all vehicle
      types observed. Drivers of the Honda vehicles with belt reminders viewed the
      system very favorably, and nearly 90 percent said they would want one in their
      next vehicle. The reminder was perceived to be most effective by part-time belt
      users; 81 percent of part-time users said they now use belts more often, compared
      with 32 percent of respondents who said they always use belts and 18 percent who
      use belts occasionally. CONCLUSION: Belt reminders in Honda as well as Ford
      vehicles are increasing. Although the increase is moderate (5.6 percentage
      points), on a national level it could have prevented at least 736 driver deaths
      in 2004.

PMID- 17497515
TI  - How important is vehicle safety in the new vehicle purchase/lease process for
      fleet vehicles?
AB  - OBJECTIVE: Despite the potential benefits that fleet vehicle purchase decisions
      could have on road safety, the role that vehicle safety plays in fleet managers'
      purchase decisions is poorly understood. METHODS: In this study, fleet managers
      from Sweden and Spain completed a questionnaire regarding the importance of
      vehicle safety in the new vehicle purchase/lease process and the importance that
      is placed on safety options/features relative to other convenience and comfort
      features. RESULTS: The findings of the current study suggest that vehicle safety
      is generally not the primary consideration in the vehicle purchase process and is
      consistently outranked by factors such as price and dependability/reliability.
      For example, when asked to indicate the vehicle factors that are included in
      their company's criteria for purchasing/leasing a new vehicle, fleet managers
      from both Sweden and Spain were more likely to list the vehicle's price,
      reliability, running costs, size, and fuel consumption than the vehicle's safety
      (defined as the vehicle's EuroNCAP rating/other safety reports). In addition, the
      findings of this study suggest that the importance of vehicle safety did not
      differ across the two countries. For example, there was no significant difference
      in the proportion of fleet managers who indicated that EuroNCAP ratings were part
      of their official policy across the two countries. CONCLUSION: The findings
      highlighted the need to educate fleet managers about vehicle safety in the new
      vehicle purchase/lease process. In addition, vehicle safety information, such as
      EuroNCAP results or other crash test results need to be promoted more widely and
      effectively so that they play a more prominent role in their new vehicle choices.

PMID- 17497516
TI  - Knowledge, attitude, and practice of Nigerian commercial motorcyclists in the use
      of crash helmet and other safety measures.
AB  - OBJECTIVE: This study was designed to evaluate the knowledge, attitude, and
      practice of some commercial motorcyclists in Nigeria in the use of crash helmet
      and other cycling safety measures. METHODS: At randomly selected commercial
      motorcycle parks from two South Western Nigerian locations (Lagos and Ile-Ife),
      we obtained verbal consent from commercial motorcyclists (randomly selected) and
      thereafter administered structured questionnaires to consenting motorcyclists.
      The questionnaire sought to know the respondents' biodata (age, gender, and
      educational attainment inclusive), cycling background, and experience (trainer,
      duration of training and cycling, and history of crashes). Furthermore, risk
      factors and practices like alcoholism, maintenance history of the motorcycle,
      maximum number of pillion passengers carried, and use of crash helmet were
      elicited. Respondents' knowledge of available safety measures was also
      investigated. Data was entered into an IBM compatible computer and analyzed using
      the SPSS 11.0 statistical software. Statistical significance was inferred at p
      value<0.05. RESULTS: There were 224 male respondents aged 15-58 years. Their peak
      age was 25-29 years and mean 35.1+/-8.9 years; 8.4% had no formal education;
      10.3% received formal training but the majority were either trained by self
      (35.5%) or an acquaintance (34.6%). Training lasted<or=1 week in 21.5% of the
      respondents and<or=3 weeks in 43%. Close to half (48.6%) of cyclists admitted
      carrying more than one (2-4) pillion passenger; 64 (30%) volunteered positive
      history of alcohol consumption. Only 20% supplied a crash helmet as a known
      safety device and 23.8% had a helmet on at the time the study was conducted. The
      majority (67.3%) favored the enforcement of crash helmet while others would
      reject the idea; 45.8% of the cyclists have been involved in crashes at one time
      or the other. Most of the crashes occurred with a motor vehicle or as a lone
      accident while they attributed most of the accidents to bad roads and failure to
      observe road signs. CONCLUSION: Commercial motorcycling is essentially done by
      males who have not received formal training for the job; hence, they lack
      adequate knowledge and practice of road safety measures. Additionally, bad roads
      appear to also contribute to frequent crashes. However, the need to enforce all
      existing laws related to motorcycling is evident.

PMID- 17497517
TI  - Study of vehicle speeds on a major highway in Ghana: implication for monitoring
      and control.
AB  - OBJECTIVE: Vehicular speeds have been identified to be at the core of road
      accident severity and frequency globally. Whereas speed control is a fundamental
      priority and the cornerstone of road safety in the developed world, the subject
      is at rudimentary stages in most developing countries thus making research into
      vehicle speeds in developing nations imperative. The main aim of the study was to
      establish two major speed parameters, namely the mean speed and dispersion, and
      their implications for more extensive and long-term speed monitoring in Ghana.
      METHODS: Research workers stationed themselves in a parked car and used a radar
      gun to unobtrusively measure the travelling speeds of 4,163 vehicles over two 24
      hour periods at two separate sites on one of the main inter-urban roads (Accra
      Kumasi). Both sites were settled areas with posted speed limits of 50 km/hr.
      RESULTS: Over 95% of vehicles travelled above the posted speed limit of 50 km/hr.
      Vehicles on an average travelled at 87 km/hr, (95% CI=87, 88). Variation in
      speeds was wide, with a standard deviation of 18 km/hr for all classes of
      vehicles, and with a range of 40 to 187 km/hr. The highest vehicular speed was
      associated with the private car (97.6+/-18.3 km/hr) followed by large buses
      (93.6+/-13.3 km/hr) and the least was with heavy trucks (73.8+/-12.9 km/hr).
      CONCLUSION: The excessive vehicular speeds coupled with the wide speed variations
      explain in part the high incidence of traffic crashes and fatalities on the Accra
      Kumasi highway. An integrated speed monitoring and control program, and
      realigning the highway to by-pass small and medium settlements would be required
      as a long-term measure for the reduction of speed-related road traffic crashes,
      fatalities, and injuries in Ghana.

PMID- 17497518
TI  - Preventing alcohol-related convictions: the effect of a novel curriculum for
      first-time offenders on DUI recidivism.
AB  - OBJECTIVE: To determine whether DUI offenders can better avoid future drinking
      and driving by controlling their vehicle usage rather than by controlling their
      drinking. METHODS: Using a randomized experimental post-test only design, 9,571
      first-time DUI offenders were randomly assigned to receive one of two 12-hour
      educational programs: a traditional DUI curriculum or the PARC (Preventing
      Alcohol-Related Convictions) curriculum, which uses a novel theoretical approach
      to preventing DUI recidivism. Whereas traditional programs focus on participants
      controlling their drinking to avoid future drinking and driving, the PARC
      curriculum focuses on participants controlling their driving. Instead of trying
      to control alcohol consumption after driving to a drinking venue (previously
      found to be a flawed strategy), PARC teaches students to make a decision before
      leaving home not to drive to a drinking event, thus greatly limiting the
      possibility of drinking and driving. Driving records were obtained from the
      Florida Department of Motor Vehicles using driver's license numbers to assess DUI
      recidivism rates among the students in the PARC and Traditional curricula for the
      first year following program participation and again at 2 years post
      intervention. RESULTS: Binary logistic regression analyses revealed that
      offenders receiving the PARC curriculum exhibited significantly lower 1-year and
      2-year recidivism rates than those receiving the Traditional curriculum. The
      effect was consistent across two different measures of recidivism, and across
      gender, race, ethnicity, and location. CONCLUSION: Results suggest that the PARC
      educational approach may be more effective than the traditional approach in
      reducing DUI recidivism.

PMID- 17497519
TI  - Changes in driving behavior and cognitive performance with different breath
      alcohol concentration levels.
AB  - OBJECTIVE: This study examines the changes in driving behavior and cognitive
      performance of drivers with different breath alcohol concentration (BrAC) levels.
      METHODS: Eight licensed drivers, aged between 20 and 30 years, with BrAC levels
      of 0.00, 0.25, 0.4 and 0.5 mg/l performed simulated driving tests under high- and
      low-load conditions. Subjects were asked to assess their subjective psychological
      load at specified intervals and perform various tasks. The outcome was measured
      in terms of reaction times for task completion, accuracy rates, and driver's
      driving behavior. RESULTS: The effects of BrAC vary depending on the task.
      Performance of tasks involving attention shift, information processing, and short
      term memory showed significant deterioration with increasing BrAC, while
      dangerous external vehicle driving behavior occurred only when the BrAC reached
      0.4 mg/l and the deterioration was marked. CONCLUSION: We can conclude that the
      cognitive faculty is the first to be impaired by drinking resulting in
      deteriorated performance in tasks related to divided attention, short-term
      memory, logical reasoning, followed by visual perception. On the other hand,
      increasing alcohol dose may not pose an immediate impact on the external vehicle
      driving behavior but may negatively affect the driver's motor behavior even at
      low BrAC levels. Experience and will power could compensate for the negative
      influence of alcohol enabling the drivers to remain in full steering control.
      This lag between alcohol consumption and impaired driving performance may mislead
      the drivers in thinking that they are still capable of safe steering and cause
      them to ignore the potential dangers of drunk driving.

PMID- 17497520
TI  - Efficacy of side airbags in reducing driver deaths in driver-side car and SUV
      collisions.
AB  - OBJECTIVE: To estimate the efficacy of side airbags in preventing driver deaths
      in passenger vehicles struck on the driver side. METHODS: Risk ratios for driver
      deaths per driver-side collision were computed for side airbag-equipped cars and
      SUVs, relative to vehicles without side airbags. Driver fatality ratios also were
      calculated for the same vehicles in front and rear impacts, and these were used
      to adjust the side crash risk ratios for differences in fatality risk unrelated
      to side airbags. Risk ratios were calculated separately for side airbags
      providing torso-only protection and side airbags with head protection; almost all
      head protecting airbags also had airbags protecting the torso. RESULTS: Car
      driver death risk in driver-side crashes was reduced by 37 percent for head
      protecting airbags and 26 percent for torso-only side airbags. Car driver death
      risk was reduced for older and younger drivers, males and females, and drivers of
      small and midsize cars, and when the striking vehicle was an SUV/pickup or a
      car/minivan. Death risk for drivers of SUVs was reduced by 52 percent with head
      protecting side airbags and by 30 percent with torso-only airbags. The
      effectiveness of side airbags could not be assessed for pickups and minivans due
      to the small number of these vehicles with airbags involved in crashes.
      CONCLUSION: Side airbags substantially reduce the risk of car and SUV driver
      death in driver-side collisions. Making side airbags with head protection
      available to drivers and right front passengers in all passenger vehicles could
      reduce the number of fatalities in motor vehicle crashes in the United States by
      about 2,000 each year.

PMID- 17497521
TI  - Lower extremity injuries in children seated in forward facing child restraint
      systems.
AB  - OBJECTIVE: The lower extremity is among the most frequently injured body regions
      for children restrained by forward facing child restraint systems (FFCRS),
      accounting for 28% of their clinically significant injuries, defined as AIS 2 and
      greater injuries excluding concussions. Despite the prevalence of these injuries,
      the current U.S. Motor Vehicle Safety Standard governing FFCRS (FMVSS 213) does
      not provide a direct assessment of the biomechanical risk of lower extremity
      fracture nor do the current pediatric test devices provide adequate
      instrumentation to detect the risk of such injuries. Before improvements can be
      made to the anthropometric test devices (ATDs) or test procedures to address
      these limitations, understanding of the sources and mechanisms of these injuries
      is necessary. Therefore, the objective of this study was to document location,
      source, and crash circumstances of lower extremity injuries in children seated in
      FFCRS. METHODS: Utilizing two sources of data, PCPS and CIREN, 20 in-depth
      investigations of crashes involving children seated in FFCRS with lower extremity
      injuries were reviewed to determine the nature of the injuries and the
      circumstances under which they occurred. RESULTS: Injuries below the knee were
      the most common, particularly to the tibia/fibula, and they most often occurred
      due to interaction with the vehicle seatback in front of the child's seating
      position. These injuries were sustained most commonly in frontal impacts although
      interaction with the seatback also occurred in other crash types. This
      interaction with the seatback was exacerbated by possible contributing factors
      such as intrusion of the front seatback into the child's occupant space or FFCRS
      misuse resulting in increased excursion of the child during impact. CONCLUSIONS:
      This review of cases of children in FFCRS with AIS 2 and greater lower extremity
      injury points to the role of the seatback in the occurrence of these injuries,
      suggesting the need to consider this interaction in the seatback design process
      and to adequately represent this interaction in regulatory procedures assessing
      the performance of child restraints.

PMID- 17497522
TI  - Injuries in special transportation services for elderly and disabled--a multi
      methodology approach to estimate incidence and societal costs.
AB  - OBJECTIVE: Previous research has shown that elderly and disabled travelers using
      Special Transportation Services (STS) are injured without being involved in a
      vehicle crash. In order to estimate the true costs for these vehicle-related
      injuries, the focus needs to be adjusted towards an incident/traveler-oriented
      perspective. The aim of the project was thus to utilize such a perspective, in
      order to make a best estimation of the true costs for injury incidents, related
      to STS in Sweden. METHODS: In order to address the chosen perspective, a mixed
      method approach was used, involving quantitative as well as qualitative research
      methods applied on four different sets of data, the hospital-based material
      (n=32), two sets of STS material (n=127), and interview-based material (n=1,000).
      RESULTS: The results showed that the injury incidence rate in STS is
      considerable, i.e., 3.2 per 100,000 trips (ranging from 1.5-1.9 in STS taxis and
      3.6-5.6 in STS special vehicles). However, this high incidence rate is not due to
      road traffic crashes, but to non-collision injury incidents involving elderly and
      frail passengers, easily sustaining injuries from minor to moderate external
      violence. Typically, this violence is affecting an older female STS user, while
      entering and exiting the vehicle. The true costs were estimated to be $35 million
      per annum or $2.6 per trip. CONCLUSION: Future injury prevention measures should
      thus focus on safety in entering and exiting procedures.

PMID- 17497523
TI  - Prevalence of alcohol and illicit drugs in blood specimens from drivers involved
      in traffic law offenses. Systematic review of cross-sectional studies.
AB  - OBJECTIVE: To determine which is the reported prevalence of alcohol and illicit
      drugs in blood specimens from drivers involved in traffic law offenses worldwide.
      METHODS: The search was performed by using several international biomedical
      databases. In order to reduce publication bias, additional publications were
      identified using further sources of information. The present review includes
      cross-sectional studies published between 1990 and 2005 in English, Spanish,
      German, Portuguese, and Italian. Only studies based on the analysis of blood
      specimens and chromatographic quantification of drugs were included. RESULTS:
      Forty-nine studies fulfilled the inclusion criteria. Eighteen were excluded
      considering practical reasons regarding limitations for a reliable interpretation
      of their results. Alcohol appears to be still the predominant substance, with the
      consideration that among drivers primarily suspected of DUID, cannabinoids are
      more prevalent. Among the illicit drugs, cannabinoids are the most commonly found
      substance. Certain trends could be identified, e.g., very low prevalence of
      cocaine in reports from Nordic countries, a high prevalence of amphetamines
      between Norwegian and Swedish studies, and low rates of THC among Australian
      studies. CONCLUSION: The results of this study should be regarded as an attempt
      to obtain more reliable data concerning the prevalence of alcohol and illicit
      drugs among drivers. To obtain a better assessment of the real current role of
      alcohol and drugs (illicit and medications), it seems strongly necessary to
      update the case-control study conducted by Borkenstein et al. in 1964, including
      now blood analyses of the whole spectrum of substances that can impair drivers.

PMID- 17497524
TI  - Longer-term effects of Washington, DC, law on drivers' hand-held cell phone use.
AB  - OBJECTIVES: To determine whether the substantial short-term declines in drivers'
      use of hand-held phones achieved in the District of Columbia (DC) were sustained
      1 year after a ban. METHODS: Drivers' daytime hand-held cell phone use was
      observed in DC and nearby areas of Virginia and Maryland, states without bans.
      Observations were conducted several months before the ban, shortly after, and 1
      year later. The number of vehicles observed in all three surveys combined was
      51,945 in DC, 36,796 in Maryland, and 43,033 in Virginia. RESULTS: The rate of
      talking on hand-held phones declined significantly from 6.1 percent before the
      law to 3.5 percent shortly after; when measured 1 year later, use was 4.0
      percent, still significantly lower than baseline. Based on increases in rates of
      talking on hand-held phones in Maryland and Virginia, longer-term phone use in DC
      was estimated to be 53 percent lower than would have been expected without the
      ban. Declines in DC were identified for drivers of vehicles registered in all
      three jurisdictions. CONCLUSIONS: In DC, there was an initial decline of about 50
      percent in drivers talking on hand-held cell phones following a ban, and this
      decline was sustained about 1 year later. After a similar ban in New York, there
      was an initial decline in phone use comparable with the initial decline in DC,
      but the decline a year after the New York ban took full effect was only about 21
      percent and not statistically significant. The potential difference in sustained
      effectiveness for the DC ban may reflect tougher enforcement in DC. Even if full
      compliance with hand-held phone bans can be achieved, the risks from drivers' use
      of hands-free phones will remain.

PMID- 17497525
TI  - A new THOR shoulder design: a comparison with volunteers, the Hybrid III, and
      THOR NT.
AB  - OBJECTIVE: Since the shoulders are rarely seriously injured in frontal or oblique
      collisions, they have been given low priority in the development of frontal
      impact crash test dummies. The shoulder complex geometry and its kinematics are
      of vital importance for the overall dummy kinematics. The shoulder complex also
      influences the risk of the safety belt slipping off the shoulder in oblique
      forward collisions. The first aim of this study was to develop a new 50th
      percentile male THOR shoulder design, while the second was to compare the new
      shoulder, mounted on a THOR NT dummy, with volunteer, THOR NT, and Hybrid III
      range of motion and stiffness data. The third aim was to test the repeatability
      of the new shoulder during dynamic testing and to see how the design behaves with
      respect to belt slippage in a 45 degrees far-side collision. METHODS: The new
      50th percentile THOR shoulder design was developed with the aid of a shell model
      of the seated University of Michigan Transportation Research Institute (UMTRI)
      50th percentile male with coordinates for joints and bony landmarks (Schneider et
      al., 1983). The new shoulder design has human-like bony landmarks for the
      acromion and coracoid processes. The clavicle curvature and length are also made
      similar to that of a male human, as is the range of motion in the anterior
      posterior, superior-inferior, and medial-lateral directions. The new shoulder
      design was manufactured and tested under the same conditions that Tornvall et al.
      (2005b) used to compare the shoulder range of motion for the volunteers, Hybrid
      III, and THOR Alpha. The new design was also tested in two dynamic test
      configurations: the first was a 0 degrees full-frontal test and the second was a
      45 degrees far-side test. The dummy tests were conducted with an R-16 seat with a
      three-point belt, the Delta V was 27.0+/-0.5 km/h and the maximum peak
      acceleration was approximately 14.6+/-0.5 g for each test. RESULTS: A new
      shoulder design with geometry close to that of humans was developed to be
      retrofitted to the THOR NT dummy. The results showed that the range of motion for
      the new shoulder complex during static loading was larger by at least a factor of
      three, for the maximum load (200 N/arm), than that of either the Hybrid III or
      the THOR NT; this means it was more similar to the volunteers' range of motion.
      It was observed that the THOR NT with the new shoulder did not slide out of the
      shoulder belt during a far-side collision. The performance of the new shoulder
      was reasonably repeatable and stable during both the static tests and the sled
      tests. CONCLUSION: A new shoulder for the THOR NT has been designed and
      developed, and data from static range of motion tests and sled tests indicate
      that the new shoulder complex has the potential to function in a more human-like
      manner on the THOR dummy.

PMID- 17497526
TI  - Health effects of airborne particulate matter: do we know enough to consider
      regulating specific particle types or sources?
AB  - Researchers and regulators have often considered preferentially regulating the
      types of ambient airborne particulate matter (PM) most relevant to human health
      effects. While few would argue the inherent merits of such a policy, many believe
      there may not yet be enough information to differentially regulate PM species.
      New evidence, using increasingly sophisticated methodologies, has become
      available in the last several years, allowing more accurate assessment of
      exposure and resultant associations with specific types of PM, or PM derived from
      different sources. Such new studies may also allow differentiation of effects
      from different chemical components in the same study against the same health
      endpoints. This article considers whether this new evidence might be adequate to
      allow us to "speciate" PM types or sources by severity of health effects. We
      address this issue with respect to two widespread sources of PM, emissions from
      motor vehicles and coal-fired power plants. Emissions from less widespread
      sources, residual oil and steel/coking facilities, are also discussed in order to
      illustrate how health effects associated with such emissions might instead be
      associated with more widespread sources when accurate exposure information is
      unavailable. Based upon evaluation of studies and methodologies which appear to
      contain the most accurate information on exposure and response to important
      emissions, including variable local emissions, it is concluded that public health
      will likely be better protected by reduction of various vehicular emissions than
      by continued regulation of the total mass of fine PM (PM <2.5 microm, or PM2.5)
      as if all PM in this mode is equitoxic. However, the knowledge base is
      incomplete. Important remaining research questions are identified.

PMID- 17497527
TI  - The temporal dynamics of ozone-induced FEV1 changes in humans: an exposure
      response model.
AB  - Although ozone is known to induce reversible decrements in forced expiratory
      volume in 1 s (FEV1), no exposure-response model has been identified that
      accurately describes the dynamics of response to the changing concentrations and
      activity patterns of normal ambient human exposure. The purpose of the current
      analysis was to identify and evaluate a dynamic model of FEV1 response using a
      large existing data set (541 volunteers, 864 exposures, 3485 FEV1 measures) with
      a wide range of exposure conditions (ozone = 0.0 to 0.4 ppm, activity level =
      rest to heavy exercise, duration = 1 to 7.6 h), including recovery in clean air.
      A previously described model containing a differential equation and a logistic
      function was modified to include a new between-subjects variance structure and
      was fitted to the data. The model described well the mean observed response data
      across the range of exposure conditions, including the periods of recovery in
      clean air. Predicted values of individual responses were distributed lognormally
      and appeared to accurately describe the distribution of observed responses. We
      observed that responsiveness to ozone decreased with age, that response was
      weakly related to body size, and that response was marginally more sensitive to
      changes in ozone concentration than to changes in minute ventilation. In summary,
      we have identified a dynamic ozone exposure-response model that accurately
      describes the temporal pattern of FEV1 response to a wide range of changing
      exposure conditions and that may have utility for predicting population responses
      to ambient exposures.

PMID- 17497528
TI  - Gas uptake in a three-generation model geometry with a flat inlet velocity during
      steady inspiration: comparison of axisymmetric and three-dimensional models.
AB  - Mass transfer coefficients were predicted and compared for uptake of reactive gas
      system using an axisymmetric single-path model (ASPM) with experimentally
      predicted values in a two-generation geometry and with a three-dimensional
      computational fluid dynamics model (CFDM) in a three-generation model geometry at
      steady inspiratory flow with a flat inlet velocity profile. The flow and
      concentration fields in the ASPM were solved using Galerkin's finite element
      method and in the CFDM using a commercial finite element software FIDAP. ASPM
      predicted average gas phase mass transfer coefficients within 25% of the
      experimental values. Numerical results in terms of overall mass transfer
      coefficients from the two models within each bifurcation unit were compared for
      two different inlet flow rates, wall mass transfer coefficients, and bifurcation
      angles. The overall mass transfer coefficients variation with bifurcation unit
      from the ASPM and CFDM compared qualitatively and quantitatively closely at lower
      wall mass transfer coefficients for both 40 degree and 70 degree bifurcation
      angles. But at higher wall mass transfer coefficients, quantitatively they were
      off in the range of 2-10% for 40 degree bifurcation angle and in the range of 4
      15% for 70 degree bifurcation angle. Both CFDM and ASPM predict the same trends
      of increase in mass transfer coefficients with inlet flow, wall mass transfer
      coefficients, and during inspiration compared to expiration. Higher mass transfer
      coefficients were obtained with a flat velocity profile compared to a parabolic
      velocity profile using ASPM. These results validate the simplified ASPM and the
      complex CFDM.

PMID- 17497529
TI  - Balloon-based in vitro MDI aerosol deposition experiments on the effects of
      mouthpiece diameter.
AB  - For this article, we studied the effects of mouthpiece diameter and flow rate on
      aerosol penetration efficiency for metered-dose inhaler (MDI) applications.
      Measurements show that increasing the mouthpiece diameter has a moderate and
      positive influence on the particle penetration efficiency of the MDI. The
      particle penetration efficiency increases monotonically with the increase of the
      mouthpiece diameter from 16 mm to 20 mm. Second, the experiments show that
      airflow rate has an apparent and significant effect on particles deposition in
      the oral airway. The reduction of the airflow rate from 90 L/min to 30 L/min
      tripled the penetration efficiency of the MDI. A new experimental system has been
      employed to measure the particles deposition in the human airways. Expansion
      balloons were used to induce airflow as well as to collect the penetrated
      particles through an airway cast. The potential advantages of the balloon-based
      experimental system are simplicity, accuracy, and cost-effectiveness.

PMID- 17497530
TI  - Comparison of particle tracking algorithms in commercial CFD packages:
      sedimentation and diffusion.
AB  - Computational fluid dynamic modeling software has enabled microdosimetry patterns
      of inhaled toxins and toxicants to be predicted and visualized, and is being used
      in inhalation toxicology and risk assessment. These predicted microdosimetry
      patterns in airway structures are derived from predicted airflow patterns within
      these airways and particle tracking algorithms used in computational fluid
      dynamics (CFD) software packages. Although these commercial CFD codes have been
      tested for accuracy under various conditions, they have not been well tested for
      respiratory flows in general. Nor has their particle tracking algorithm accuracy
      been well studied. In this study, three software packages, Fluent Discrete Phase
      Model (DPM), Fluent Fine Particle Model (FPM), and ANSYS CFX, were evaluated.
      Sedimentation and diffusion were each isolated in a straight tube geometry and
      tested for accuracy. A range of flow rates corresponding to adult low activity
      (minute ventilation = 10 L/min) and to heavy exertion (minute ventilation = 60
      L/min) were tested by varying the range of dimensionless diffusion and
      sedimentation parameters found using the Weibel symmetric 23 generation lung
      morphology. Numerical results for fully developed parabolic and uniform (slip)
      profiles were compared respectively, to Pich (1972) and Yu (1977) analytical
      sedimentation solutions. Schum and Yeh (1980) equations for sedimentation were
      also compared. Numerical results for diffusional deposition were compared to
      analytical solutions of Ingham (1975) for parabolic and uniform profiles.
      Significant differences were found among the various CFD software packages and
      between numerical and analytical solutions. Therefore, it is prudent to validate
      CFD predictions against analytical solutions in idealized geometry before
      tackling the complex geometries of the respiratory tract.

PMID- 17497532
TI  - Cell morphological ultrastructural changes in various organs from mice exposed by
      inhalation to sulfur dioxide.
AB  - Sulfur dioxide (SO2) is a common air pollutant, present in low concentrations in
      the community air as well as in higher concentrations in some workplaces. Our
      previous studies demonstrated that SO2 can cause oxidative stress and DNA damage
      to multiple organs of mice. However, there was no direct proof if and how the
      morphological changes are caused by SO2. In this study, the ultrastructural
      morphologies of lungs, livers, spleens, testis, brains, hearts, and kidneys from
      mice exposed by inhalation to SO2 at 28.00 +/- 1.98 and 56.00 +/- 3.11 mg/m3 were
      observed with electron microscopy. Our results show that (1) type II alveolar
      cells of lungs in SO2-exposure groups had obvious pathological changes including
      vacuolation of osmiophilic multilamellar bodies, a decrease in microvilli content
      and mitochondrial pyknosis or swelling, as well as various changes in the
      structure of the nucleus and chromatin. Meanwhile obvious changes in the
      mitochondrial and nuclear compartments, in type II alveolar cells were also
      observed. (2) A series of pathological changes was discovered in hepatic cells in
      SO2-exposure groups, such as swelling of the nucleus, dispersion of lipid
      droplets, degenerated mitochondria, and dilatation of rough endoplasmic
      reticulum. For mice exposed to SO2 at 56 mg/m3, necrosis of hepatocytes with
      unclear karyotheca or nearly dissolved karyotheca and decreases in organelles
      were observed. (3) The numbers of apoptotic splenocytes from mice exposed to SO2
      were increased by SO2 inhalation in a dose-dependent manner. (4) In SO2-exposure
      groups, some of the cerebral cortex neurons, many glial cells and nerve fibers
      were damaged. (5) Mitochondrial swelling, decrease or disappearance of
      mitochondria crista, myocardial myofibril disorder, various changes of nucleus
      and chromatin, intercalated discs dissociation, and endothelium edema caused by
      SO2 exposure in heart tissues were found. In addition, other effects, such as
      myofibrillar fragmentation and dissolution, some myocardial cell membranes
      breach, and inflammatory cell infiltration, were observed in groups exposed to
      SO2 at 56 mg/m3. (6) SO2 exposure induced serious ultrastructural lesions in
      renal proximal tubular lining cells; moreover glomeruli and distal tubular lining
      cells were damaged in a dose-dependent manner. (7) Compared with the control
      group, the basement membranes, various seminiferous cells, as well as
      spermatozoa, and Sertoli cells of testes were altered in the SO2-exposure groups
      in a dose-dependent manner. In the aggregate, these results lead to a conclusion
      that inhalation of SO2 can cause the ultrastructure cellular damage of multiple
      organs in mice. Thus, inhalation of sulfur dioxide appears to be not only toxic
      to the respiratory system, but also a systemic toxin as well.

PMID- 17497531
TI  - Smokers have reduced nitric oxide production by conducting airways but normal
      levels in the alveoli.
AB  - Air exhaled by cigarette smokers contains reduced amounts of nitric oxide (NO).
      Measurement of NO at different expiratory flow rates permits calculation of NO
      production by the conducting airways (Vaw(NO)) and alveolar concentration of NO
      (P(ALV)). An independent measurement of diffusing capacity of the alveolar
      compartment (D(LNO)) multiplied by P(ALV) allows calculation of NO production by
      the alveoli (V(LNO)). Twelve asymptomatic cigarette smokers and 22 age-matched
      nonsmokers had measurements of D(LNO) and expired NO at constant expiratory flow
      rates varying from 60 to 1500 ml/s. Vaw(NO) in smokers was only 22 +/- 11 nl/min
      (mean +/- standard deviation, SD) compared to 70 +/- 37 nl/min in nonsmokers (p <
      .0001). In contrast, V(LNO) showed no significant difference (smokers: 203 +/-
      104 nl/min, nonsmokers: 209 +/- 74 nl/min, p = .86). These data show that the
      diminished NO expired by smokers results from diminished NO production by the
      tissues of the conducting airways but normal values produced by the alveoli.

PMID- 17497533
TI  - Detection of changes in alveolar macrophage iron status induced by select PM2.5
      associated components using iron-response protein binding activity.
AB  - The extent of adverse health effects, including induction/exacerbation of
      infectious lung disease, arising from entrainment of equivalent amounts (or
      exposure to a fixed increment) of fine particulate matter (PM2.5) can vary from
      region to region or city to city in a region. To begin to explain how differing
      effects on host resistance might arise after exposure to PM2.5 from various
      sites, we hypothesized that select metals (e.g., V, Al, and Mn) in each PM2.5
      caused changes in alveolar macrophage (AM) Fe status that, ultimately, would lead
      to altered antibacterial function. To test this, iron-response protein (IRP)
      binding activity in a rat AM cell line was assessed after exposure to Fe alone
      and in conjunction with V, Mn, and/or Al at ratios of V:Fe, Al:Fe, or Mn:Fe
      encountered in PM2.5 samples from New York City, Los Angeles, and Seattle.
      Results indicated that V and Al each significantly altered IRP activity, though
      effects were not consistently ratio-(i.e., dose-) dependent; Mn had little impact
      on activity. We conclude that the reductions in Fe status detected here via the
      IRP assay arose, in part, from effects on transferrin-mediated Fe3+ delivery to
      the AM. Ongoing studies using this assay are allowing us to better determine: (1)
      whether mass (and/or molar) relationships between Fe and V, Al, and/or Mn in any
      PM2.5 sample consistently govern the extent of change in AM Fe status; (2) how
      much any specified PM2.5 constituent (metal or nonmetal) contributes to the
      overall disruption of Fe status found induced by an intact parent sample; and (3)
      whether induced changes in binding activity are relatable to other changes
      expected to occur in the AM, that is, in IRP-dependent mRNA/levels of
      ferritin/transferrin receptor and Fe-dependent functions. These studies
      demonstrate that pollutant-induced effects on lung cell Fe status can be assessed
      in a reproducible manner using an assay that can be readily performed by
      investigators who might otherwise have no access to other very costly analytical
      equipment, such as graphite atomic absorption or x-ray fluorescence
      spectro(photo)meters.

PMID- 17497534
TI  - Tissue distribution of manganese in iron-sufficient or iron-deficient rats after
      stainless steel welding-fume exposure.
AB  - Welders can be exposed to high levels of manganese through welding fumes.
      Although it has already been suggested that excessive manganese exposure causes
      neurotoxicity, called manganism, the pathway of manganese transport to the brain
      with welding-fume exposure remains unclear. Iron is an essential metal that
      maintains a homeostasis in the body. The divalent metal transporter 1 (DMT1)
      transports iron and other divalent metals, such as manganese, and the depletion
      of iron is known to upregulate DMT1 expression. Accordingly, this study
      investigated the tissue distribution of manganese in iron-sufficient and iron
      deficient rats after welding-fume exposure. The feeding of an iron-deficient diet
      for 4 wk produced a depletion of body iron, such as decreased iron levels in the
      serum and tissues, and upregulated the DMT1 expression in the rat duodenum. The
      iron-sufficient and iron-deficient rats were then exposed to welding fumes
      generated from manual metal arc stainless steel at a concentration of 63.5 +/-
      2.3 mg/m3 for 2 h per day over a 30-day period. Animals were sacrificed on days
      1, 15, and 30. The level of body iron in the iron-deficient rats was restored to
      the control level after the welding-fume exposure. However, the tissue
      distributions of manganese after the welding-fume exposure showed similar
      patterns in both the iron-sufficient and iron-deficient groups. The concentration
      of manganese increased in the lungs and liver on days 15 and 30, and increased in
      the olfactory bulb on day 30. Slight and heterogeneous increases of manganese
      were observed in different brain regions. Consequently, these findings suggest
      that the presence of Fe in the inhaled welding fumes may not have a significant
      effect on the uptake of Mn into the brain. Thus, the condition of iron deficiency
      did not seem to have any apparent effect on the transport of Mn into the brain
      after the inhalation of welding fumes.

PMID- 17497535
TI  - Inhalation exposure to formaldehyde and toluene in the same occupational and
      consumer setting.
AB  - Formaldehyde, a natural component of all mammalian cells, is metabolized to
      carbon dioxide. It is a colorless gas used as a preservative and a reactant in
      chemical processes in a wide variety of commercial and consumer products. Toluene
      is an organic solvent also used in a wide variety of commercial and consumer
      products. There is a growing concern that chemical exposure from consumer
      products including cosmetics adds to the overall toxic exposure bioburden. This
      study was designed to quantify the actual amount of formaldehyde and toluene
      exposure to professional nail technicians and their customers during the
      application of cosmetic nail products containing either formaldehyde or toluene.
      Formaldehyde concentrations were measured on workers and consumers using treated
      silica gel absorption tubes. Formaldehyde concentrations varied between 0.0012
      and 0.0038 ppm. The results of this study clearly demonstrate that neither
      workers nor consumers are at any additional risk from exposure to formaldehyde or
      toluene in cosmetic nail products beyond daily exposure from commercial products
      in a work setting and in the home.

PMID- 17497536
TI  - Pesticide-initiated idiopathic environmental intolerance in South Korean farmers.
AB  - This study was designed to study patients with intolerance to pesticide smells.
      Ten subjects chosen were complaining of vague symptoms such as headache,
      dizziness, fatigue, nausea, vomiting, abdominal pain, myalgia, flu-like symptoms,
      etc., whenever exposed to the pesticide smells even at low intensity. To
      determine whether the etiology of this kind of pesticide hypersensitivity was of
      organic or psychiatric nature, all the subjects underwent tests as follows:
      complete blood cell count, urinalysis, and blood chemistry as routine tests;
      esophogastroduodenoscopy and abdomen ultrasonography for the gastrointestinal
      symptoms; chest x-ray, pulmonary function tests, and electrocardiography for the
      respiratory and/or cardiac symptoms; nerve conduction velocity and brain magnetic
      resonance imaging (MRI) for peripheral and central nerve system symptoms; and K
      WAIS, Rey-Kim memory test, Rorschach, Mini Mental State Examination (MMSE), and
      Minnesota Multiphasic Personality Inventory (MMPI) for psychoanalysis. Of the 10
      cases in which the chief complaint was headache, symptoms of two cases were
      caused by maxillary sinusitis. Another two showed typical multiple chemical
      sensitivity (MCS) or idiopathic environmental intolerance (IEI). Six out of the
      10 cases, whose symptoms closely resembled the others, did not conclusively meet
      the criteria of classic MCS or IEI. The subjects of this case shared vague fears,
      both fear of pesticides and hypochondriasis. Some subjects faced financial
      insecurity and social uncertainty; others felt uneasy about the future of their
      farming life. Thus, to help verify the causes of MCS or IEI, which is strongly
      suggestive of pesticide smells, diagnosis needs a dual approach: on the anima and
      soma. Psychoanalysis can delve into the mental status of the patients to see
      whether the patients are aware of their symptoms. Clinical tests can see through
      the physical structure and functions of the organs on which patients' complaints
      are centered.

PMID- 17497537
TI  - The importance of troponin-I as a predictor of cardiac injury caused by carbon
      monoxide poisoning.

PMID- 17497539
TI  - NNK is not insoluble in water.

PMID- 17497542
TI  - Treatment outcome predictors for cocaine dependence.
AB  - Over the past decade, a large number of potential medications have been examined
      in clinical trials for cocaine dependence. Unfortunately, no effective
      pharmacotherapies for cocaine dependence have been found to date. Although
      effective treatments for cocaine dependence are still being investigated, a few
      variables have been found to significantly predict cocaine treatment response.
      These variables include cocaine use variables, such as days of cocaine use in the
      month before treatment, baseline urine cocaine results, and cocaine withdrawal
      symptoms. Comorbid depression and alcohol use have also been shown to be risk
      factors for relapse. Among personality variables, impulsivity and similar
      personality traits may predict treatment response. Initial promising findings
      with genetic polymorphism, brain activation, and stress response have also been
      found and need to be replicated in future studies.

PMID- 17497543
TI  - Comparison of Health Realization and 12-Step treatment in women's residential
      substance abuse treatment programs.
AB  - The purpose of this study was to compare a relatively new therapeutic option for
      substance abuse treatment, Health Realization, and 12-Step approaches offered in
      women's residential programs. The study was sponsored by a large California
      county's Department of Alcohol and Drug Services, which had offered Health
      Realization treatment for a number of years. This study constitutes the first
      systematic evaluation of Health Realization as a substance abuse treatment
      program for adult women in a residential treatment setting. This was a randomized
      study with two observations-admission and 9 months post-admission. The results
      showed that clients in both Health Realization and 12-Step treatment exhibited
      comparable outcomes on domains such as substance use, criminal justice
      involvement, employment, housing, adverse effects of substance use and
      psychological well being. Substance use declined significantly between admission
      and follow-up in both treatment groups, irrespective of duration of treatment.
      Similarly, adverse effects of substance use declined between admission and 9
      month follow-up. Health Realization and 12-Step treatment offered comparable
      benefits for women in residential substance abuse treatment programs.

PMID- 17497544
TI  - Examining drug treatment entry patterns among young injection drug users.
AB  - Using a longitudinal state data base, 1996-2002, of all Injection Drug Users
      (IDU) (n = 37,227) admissions to all state-licensed drug treatment programs, this
      study examined differences in drug treatment entry patterns between younger IDUs
      (ages 18-25) compared to middle-age IDUs (ages 26-39) and older IDUs (over 40
      years of age). Most of the younger IDUs were male, unemployed, and dependent on
      heroin. After controlling for factors known to affect type of drug treatment
      entered, younger IDUs were significantly more likely than their older
      counterparts to only use detoxification services and not enter additional
      treatment. Further, younger IDUs were significantly less likely to enter
      methadone maintenance and significantly more likely to enter residential
      treatment compared to older IDUs. Development of strategies to promote transition
      from detoxification to more comprehensive treatments and especially to methadone
      maintenance treatment is warranted.

PMID- 17497545
TI  - Access to drug abuse treatment under Treatment on Demand policy in San Francisco.
AB  - OBJECTIVES: We evaluated whether implementation of Treatment on Demand (TOD)
      policy in San Francisco was associated with improved access to drug abuse
      treatment. METHODS: Data came from San Francisco's treatment program waiting list
      over 4 years spanning the implementation of TOD policy. Access measures were
      monthly applicants waiting and days waited by treatment admissions. Quantitative
      analyses with 69 treatment facilities contrasted those receiving vs. not
      receiving TOD funds. Qualitative data came from interviews with facility
      administrators. RESULTS: There was a small statistically significant decline in
      monthly waiting lists in the number of people waiting for treatment during the
      study period. The days waited by those admitted to treatment, however,
      significantly increased in TOD-funded facilities. Facilities used varied criteria
      for completing the access measures, which limit the utility of the measures.
      CONCLUSIONS: Access to treatment improved slightly with implementation of TOD
      policy.

PMID- 17497546
TI  - Substance use criminality, and social support: an exploratory analysis with
      incarcerated women.
AB  - This exploratory study examined the extent to which substance use and criminality
      influence perceptions of social support. A stratified random sample of 100
      incarcerated women in one Kentucky prison participated in face-to-face
      interviews. Overall, findings indicate that perceptions of social support
      significantly and negatively correlated with women's severity of substance use
      and criminal involvement. In addition, the breadth of a respondent's social
      network was negatively related to the age of first incarceration and to the
      severity of alcohol and drug use. Findings from this study suggest there is a
      relationship between severity of substance use, criminality, and perceptions of
      social support. Implications for substance use research and practice are
      discussed.

PMID- 17497547
TI  - Correlates of drug treatment program staff's self efficacy to support their
      clients' hepatitis C virus (HCV) related needs.
AB  - Drug treatment staff are uniquely situated to support their clients' HCV related
      needs, and those with greater self efficacy to do so are more likely to provide
      this support. Using data collected from staff (N = 140) in 6 drug treatment
      programs in New York City, we determined the correlates of this self efficacy.
      Results indicate that medically credentialed staff and staff with more hepatitis
      C knowledge have greater self efficacy to support their clients' HCV related
      needs. There was no relationship between this self efficacy and the staff
      member's own HCV infection or that of a close relative. Efforts should focus on
      increasing staff's HCV knowledge in order to increase their confidence in
      providing HCV related support to their clients.

PMID- 17497548
TI  - Contingency Management to reduce substance use in individuals who are homeless
      with co-occurring psychiatric disorders.
AB  - Homeless shelters provide a unique opportunity to intervene with occupants who
      have substance abuse problems, as not addressing these issues may lead to
      continuation of problems playing a contributing role in homelessness. Attempts to
      implement Contingency Management (CM) with this population have often been
      complex, costly, and not straightforward to replicate in community settings. We
      conducted a randomized trial evaluating a simple, low-cost 4-week CM program for
      30 individuals seeking shelter in a community-based homeless shelter who had both
      current substance and psychiatric disorders. Behavioral assessments were
      performed at baseline, weekly, and termination of the study. Overall retention in
      the trial was high; participants assigned to CM reduced their cocaine and alcohol
      use more than those in assessment-only. This pilot trial suggests that
      application of low-cost CM procedures is feasible within this novel setting and
      may decrease substance use.

PMID- 17497549
TI  - Mental health as a mediator of gender differences in employment barriers among
      drug abusers.
AB  - Employment has been identified as an important drug abuse treatment outcome, but
      drug abusers often face a wide variety of barriers to securing stable employment.
      The employment barriers literature also reports that women and people with mental
      health problems have difficulty in obtaining employment. The current study
      examined gender differences in mental health and employment barriers in a sample
      of drug court participants. Hierarchical regression analyses were conducted to
      test the hypothesis that differences in employment barriers among drug-abusing
      males and females are mediated by differences in mental health problems. Women
      were found to have more mental health problems and employment barriers, and
      support for the mediation hypothesis was found. Implications for drug treatment
      providers are discussed.

PMID- 17497550
TI  - Are prisoner characteristics associated with therapeutic community treatment
      process?
AB  - The relationship between prisoner client characteristics and Therapeutic
      Community treatment process was examined in a male program (N = 164) and a female
      program (N = 195). Analyses were based on client reports on a multidimensional
      measure of treatment process and administrative data. Prisoner clients who are
      older or are poly-substance users had better Community Environment scores.
      Clients with children and fewer lifetime arrests had better scores on Personal
      Development and Change. Treatment process scores were comparable for clients in
      the female program and the male program. However, the association of treatment
      process with client characteristics appears stronger in the male program.

PMID- 17497551
TI  - Demographic and psychosocial characteristics of mothers using methamphetamine
      during pregnancy: preliminary results of the infant development, environment, and
      lifestyle study (IDEAL).
AB  - This study describes the psychological characteristics and caretaking
      environments of 131 women enrolled in the first longitudinal study of prenatal
      methamphetamine (MA) exposure and child development. Prenatal MA use was
      associated with lower maternal perceptions on quality of life, greater likelihood
      of substance use among family and friends, increased risk for ongoing legal
      difficulties, and a markedly increased likelihood of developing a substance abuse
      disorder. Our preliminary findings suggest that MA using women are more likely to
      have multiple, intertwined psychosocial risks that may result in maladaptive
      parenting and caregiving. These factors may impact the developmental outcomes of
      affected children.

PMID- 17497552
TI  - Predictors of injection drug use cessation among Puerto Rican drug injectors in
      New York and Puerto Rico.
AB  - More than half of all AIDS cases among Puerto Ricans have been attributed to
      injection drug use. Predictors of injection drug use cessation were examined
      among Puerto Rican injection drug users (IDUs) in New York and Puerto Rico.
      Analysis of baseline and 6-month follow-up data from 670 IDUs in NY and 316 in PR
      showed that 47% NY and 20% in PR reported cessation of injection at follow-up (p
      < .001). In multivariate analyses, having been in drug treatment since baseline
      was the only significant predictor of cessation for both sites (NY: AOR = 1.80;
      PR: AOR = 3.10). Increasing availability of methadone maintenance treatment,
      especially in PR, was indicated.

PMID- 17497553
TI  - Cognitive performance in light current users and ex-users of ecstasy (MDMA) and
      controls.
AB  - Previous research has shown that heavy users of ecstasy (MDMA) may suffer
      impaired cognitive functioning, and the present study set out to investigate
      whether such impairment might also be found in light users or ex-users of MDMA.
      Sixty subjects, comprising 20 current light users, 20 ex-users, and 20 non-users
      of ecstasy, were tested on an extensive battery of cognitive tests. Current light
      users of ecstasy achieved significantly lower scores on the overall cognitive
      test battery than did the non-users (p = .011), though there were no significant
      differences on any individual subtests. However, the scores obtained by the ex
      users of ecstasy did not differ significantly from those of the non-users. It was
      concluded that current light users of ecstasy show a small but significant
      cognitive impairment, but that no such impairment is detectable in ex-users who
      had abstained from the drug for at least 6 months.

PMID- 17497555
TI  - Factors associated with public injecting among users of Vancouver's supervised
      injection facility.
AB  - BACKGROUND: We evaluated factors associated with public drug injection among a
      cohort of injection drug users (SEOSI) originally recruited from within
      Vancouver's supervised injecting facility (SIF). METHODS: We used univariate
      statistics and logistic regression to examine factors associated with public drug
      injection among SEOSI participants. FINDINGS: Between June 2004 and July 2005,
      714 IDU were followed up as part of SEOSI. In multivariate analyses, factors
      associated with public drug injection included homelessness (adjusted odds ratio
      (aOR) = 3.10; p < .001), syringe lending (aOR = 5.39; p < .001), requiring help
      injecting (aOR = 1.60; p = .05), and reporting that wait times affected frequency
      of SIF use (aOR = 3.26; p < .001). INTERPRETATION: Persistent public injection
      was independently associated with elevated HIV risk behaviors, as well as
      programmatic factors that limit SIF use. SIF program expansion may further help
      to reduce persistent risk behaviors and the community concerns related to public
      injection drug use.

PMID- 17497554
TI  - Differences in prevalence of prescription opiate misuse among rural and urban
      probationers.
AB  - We compared the prevalence of prescription opiate misuse among 2 cohorts of
      felony probationers (N = 1525). Multiple logistic regression was utilized to
      determine the independent correlates of prescription opiate misuse among rural (n
      = 782) and urban (n = 743) probationers participating in an HIV-intervention
      study. After adjustment for differences in demographic and drug use
      characteristics, rural participants were almost five times more likely than their
      urban counterparts to have misused prescription opiates. The prevalence of
      prescription opiate misuse was significantly higher among the rural probationers;
      however, given the paucity of illicit opiates and relatively recent emergence of
      prescription opiates in rural areas, rural substance abuse treatment may be ill
      prepared to treat prescription opiate misuse.

PMID- 17497556
TI  - History of reported head trauma in a sample of women in substance abuse
      treatment.
AB  - OBJECTIVES: To determine the prevalence of history of head trauma, causes of such
      trauma, and the associated chronic sequelae in a sample of women in chemical
      dependency treatment programs. PARTICIPANTS: A total of 2,198 females of varied
      ethnic and racial backgrounds participating in substance abuse treatment
      programs. MEASURE: Head trauma questionnaire eliciting information via subject
      report on history of head trauma, cause of such head trauma, and specific chronic
      sequelae resulting from the head trauma. RESULTS: Nine hundred thirty (42.3%) of
      the subjects reported history of at least one head trauma; 754 (34.3%) reported
      the head trauma having had occurred by another person. Data on reported chronic
      residual sequelae from the head trauma as well as breakdown by ethnic/racial
      group is also provided. CONCLUSIONS: The prevalence of history of head trauma
      along with reported sequelae as a result of such in this sample suggests that
      head trauma may certainly be a significant factor in persons presenting for
      substance abuse treatment. Assessing for a history of head trauma and associated
      sequelae in persons presenting in substance abuse treatment programs may be
      clinically appropriate as such sequelae have been found to adversely affect
      treatment progress. Further discussion on implications of the results of this
      research as well as discussion on further research in the area are provided.

PMID- 17497557
TI  - The development and initial validation of the identification of alcohol
      dependence in women scale.
AB  - The purpose of this research was to develop the Identification of Alcohol
      Dependence in Women (IADW) Scale, which is a 51-question instrument, designed to
      discriminate between alcohol and non-alcohol dependent women. Questions focus on
      physical, psychological, family and home life, and use of alcohol. Initial
      testing of the IADW Scale provides preliminary evidence that it is reliable, has
      content validity, and is capable of correctly classifying group membership with
      accuracy. Eighty-six percent of the cases in the alcohol dependent group and 98%
      of the non-alcohol dependent group were correctly classified using direct and
      stepwise methods of discriminant analysis.

PMID- 17497558
TI  - Evidence that response inhibition is a primary deficit in ADHD.
AB  - The present study examined response inhibition in children with attention deficit
      hyperactivity disorder (ADHD; n = 58) and controls (n = 84) using three go/no-go
      tests -- one with high working memory demand (cognitive), one with low working
      memory demand (simple), and one with rewards and response costs (motivation
      linked) in which emphasis was on reward for responding to "go" stimuli. Results
      of a repeated measure analysis of variance showed a significant effect of
      diagnosis for errors of commission for the simple, cognitive, and motivation
      linked go/no-go tests, such that children with ADHD made significantly more
      errors than controls. Furthermore, a significant effect of test was noted across
      groups, such that both children in the ADHD and control groups performed worse on
      the cognitive and motivation-linked tests than they did on the simple test. The
      diagnosis by test interaction was not significant, suggesting that ADHD
      participants showed a similar degree of impairment to that of controls,
      regardless of the degree of working memory load or feedback provided in the test.
      In children with ADHD, response inhibition appears to be a primary deficit that
      is observed even when executive function demands of tasks are minimal. Although
      increasing working memory demand appears to impede response inhibition, this
      effect is similar in ADHD and typically developing children.

PMID- 17497559
TI  - Acute effects of smoked marijuana on decision making, as assessed by a modified
      gambling task, in experienced marijuana users.
AB  - The impact of regular marijuana use on executive cognitive abilities, including
      decision making, is not well understood. While cross-sectional studies have
      suggested that substance abusers exhibit impaired decision making, as assessed by
      the Iowa Gambling Task, the direct role of marijuana use in the Gambling Task
      performance of marijuana smokers has not been well defined. In this report, we
      present data on performance on a modified Gambling Task in experienced marijuana
      users after they had smoked marijuana under controlled laboratory conditions. A
      total of 36 marijuana users, who reported smoking approximately 24 marijuana
      cigarettes per week, completed this 3-session outpatient study. During each
      session, these volunteers completed the Gambling Task once at baseline and 3
      times after smoking a single marijuana cigarette (0.0, 1.8, or 3.9% Delta9-THC).
      Marijuana cigarettes were administered in a double-blind fashion, and the
      sequence of Delta9-THC concentration was balanced across volunteers. Marijuana
      increased the time required to complete the task. However, advantageous card
      selection and money earned on the task were not disrupted by marijuana. These
      data are consistent with previous findings that indicated that speed of
      performance on tests of executive function, but not accuracy, is disrupted in
      experienced marijuana users during marijuana intoxication.

PMID- 17497560
TI  - Patients with Huntington's disease have impaired awareness of cognitive,
      emotional, and functional abilities.
AB  - The clinical literature in Huntington's disease (HD) suggests that unawareness of
      deficits is prevalent among HD patients. However, few studies have characterized
      unawareness of different types of impairment within this neuropsychiatric
      disorder. The purpose of the current study was to examine self-awareness of
      functioning across symptom domains in HD patients and to explore the association
      between impaired awareness and cognitive dysfunction. A total of 66 pairs of HD
      patients and collaterals of the patients completed symptom-rating measures
      regarding both the patients' and the collaterals' behavior. A subset of 19
      patients also underwent neurological and neuropsychological assessments. The
      results indicated that patients lacked awareness across symptom domains (i.e.,
      behavioral control, emotional control, activities of daily living), which was
      significantly greater for their perception of their own behavior than for their
      perception of their collateral's behavior. Exploratory analyses revealed
      associations between impaired self-awareness, global cognition, and deficits in
      executive functioning and memory. The current findings underscore the importance
      of examining different types of impaired awareness including both over- and
      underreporting of abilities. Future studies will benefit also from examining the
      association between awareness and cognition in larger samples.

PMID- 17497561
TI  - Mayo's Older Americans Normative Studies: Visual Form Discrimination and copy
      trial of the Rey-Osterrieth Complex Figure.
AB  - Age-adjusted normative data are presented for persons age 70-89 years for the
      Visual Form Discrimination Test and Rey-Osterrieth Complex Figure (copy trial
      only). Adjustment for the effect of education on test performance is also
      provided. These data were collected as part of Mayo's Older Americans Normative
      Studies (MOANS). The normative information provided here should prove useful for
      characterizing performance on these measures as well as comparing the person's
      performance against his or her functioning on any other test with MOANS norms.
      Limitations and unique features of the MOANS normative data are also discussed.

PMID- 17497562
TI  - Neuropsychological prediction of attrition due to death.
AB  - In aging research, attrition bias produces underestimates of cognitive decline
      and limits the interpretation of cognitive change. Using data from the Canadian
      Study of Health and Aging, we identified neuropsychological predictors of death
      among not cognitively impaired (NCI) and cognitively impaired, not-demented
      (CIND) persons. For those with NCI, two neuropsychological measures significantly
      predicted attrition, over and above age, in the short term, while age was the
      best long-term predictor. The absence of neuropsychological predictors for the
      CIND group may reflect the group's etiological heterogeneity. In future research,
      the use of a more homogeneous subset of CIND may yield additional predictors.

PMID- 17497563
TI  - Impairments in source memory for olfactory and visual stimuli in preclinical and
      clinical stages of Huntington's disease.
AB  - Individuals in preclinical and clinical stages of Huntington's disease (HD)
      demonstrate impairments in olfactory functioning. In addition, HD patients are
      impaired in source memory for verbal stimuli. A task combining both source and
      odor memory may be particularly sensitive to early changes in HD. The present
      study examined source and item memory for olfactory and visual stimuli in 10
      individuals with HD, 10 asymptomatic HD gene carriers, 8 nongene carriers who had
      a parent with HD, and 20 normal controls. During the study phase, a male and a
      female experimenter (sources) presented odors and objects to the participant in
      an alternating sequence. To assess item memory, a stimulus from the study phase
      (target) and a novel stimulus (distractor) were presented, and the participant
      was asked to choose the target. To assess source memory, the experimenter
      presented a stimulus and asked whether the male or female experimenter had
      previously presented the stimulus. Results indicate that source memory for both
      visual and olfactory stimuli was impaired in HD patients compared to normal
      controls. In asymptomatic gene carriers, however, source memory for olfactory
      stimuli, but not visual stimuli, was more impaired than in nongene carriers and
      normal controls. Furthermore, gene carriers and HD patients showed a similar
      degree of impairment in source memory for olfactory stimuli. The only significant
      impairment found in item memory was for olfactory stimuli in HD patients. These
      results suggest that source memory for olfactory stimuli may be particularly
      sensitive to neuropathological changes in preclinical stages of HD.

PMID- 17497564
TI  - A multicomponent exploration of verbal short-term storage deficits in normal
      aging and Alzheimer's disease.
AB  - Although many studies have shown diminished performance in verbal short-term
      memory tasks in normal aging and Alzheimer's disease (AD), the cognitive
      processes responsible for this verbal short-term storage (STS) impairment are
      still unclear for both populations. We explored verbal STS functioning in
      patients with AD, elderly participants, and young participants, by investigating
      a series of processes that could underlie STS impairments in normal elderly and
      AD populations. The processes we investigated were (a) the influence of lexical
      and sublexical language knowledge on short-term storage performance, (b)
      functioning of the phonological loop component via word length and phonological
      similarity effects, and (c) executive control processes (coordination and
      integration). For the AD and elderly groups, the influence of language knowledge
      on verbal STS performance and the functioning of the phonological loop were
      preserved. In contrast, the AD group showed deficits for coordination and
      integration processes. Our results suggest that the verbal STS deficit observed
      in AD patients is related to impaired executive control processes. On the other
      hand, language-related processes underlying passive storage capacity seem to be
      preserved.

PMID- 17497565
TI  - HFA and ADHD: a direct comparison on state regulation and response inhibition.
AB  - This study examined whether children with high-functioning autism (HFA) are
      easily overaroused/activated and whether children with attention
      deficit/hyperactivity disorder (ADHD) are easily underaroused/activated. This
      double dissociation was tested using a go/no-go paradigm with computer-paced fast
      and slow conditions and a self-paced condition. In the HFA group, a performance
      decline in the fast condition and slow performance in the self-paced condition
      were expected. In the ADHD group, a performance decline in the slow condition and
      fast performance in the self-paced condition were expected. No difference was
      found between groups for state regulation and response inhibition. Findings are
      discussed in the light of development, comorbidity, and subtypes.

PMID- 17497566
TI  - Context processing and negative symptoms in schizophrenia.
AB  - The objective of the study was to test the assumption that patients with a high
      level of negative symptoms show disproportionate impairments of inhibition and
      multitasking, both representing an underlying context processing mechanism. A
      total of 26 schizophrenia patients scoring high or low on negative symptoms
      (Positive and Negative Syndrome Scale) and a group of 13 healthy controls were
      assessed on measures of response inhibition (AX- Continuous Performance Task,
      Stroop Test) and multitasking (Dual Task, Trail Making Test). Only the high
      negative symptoms group showed significantly higher inhibition costs and
      multitasking costs than healthy controls. In the AX-Continuous Performance Test,
      inhibition costs exceeded context costs in patients with more severe negative
      symptoms, while in controls a tendency towards the reverse pattern emerged. There
      were no statistically significant effects involving the patient group with lower
      negative symptom scores. The pattern of results suggests that primarily patients
      with more severe negative symptoms have difficulties benefiting from contextual
      information. The deficit may manifest itself via increased multitasking costs and
      increased inhibition costs but also via reduced context costs.

PMID- 17497567
TI  - A neuropsychological profile of off-diet adults with phenylketonuria.
AB  - The metabolic disorder phenylketonuria (PKU) is treated early by a low
      phenylalanine diet. While this prevents global cognitive impairment, some
      patients still experience cognitive and neurophysiological abnormalities.
      Neuropsychological testing of early treated, currently off-diet, PKU patients
      attending an adult PKU clinic showed a reduction in the Perceptual Organization
      Index (POI), Processing Speed Index (PSI) from the Wechsler Adult Intelligence
      Scale Third Edition (WAIS-III), and Part A of the Trail Making Test for the PKU
      group relative to controls. Taken together, these results supported a profile of
      reduced information-processing speed.

PMID- 17497568
TI  - The use of indirect and opposition tests to detect simulated amnesia.
AB  - Two experiments investigated the effect of instruction to simulate memory
      impairment on performance on a word stem completion task. In addition to the
      standard control group, a second control group (divided-attention group) studied
      the target words concurrently with a digit-monitoring task. Experiment 1, using
      the indirect instruction, did not discriminate clearly between the groups.
      Experiment 2 used the opposition instruction in which participants were required
      to complete stems with words they had not seen earlier. It showed that simulators
      and controls withheld significantly more studied target items than did the
      divided-attention group. Increasing the number of study list presentations
      further increased the difference between the performance of the simulating and
      control groups and the divided-attention group. These results suggest that the
      opposition method may be useful in detecting feigned memory impairment.

PMID- 17497569
TI  - Power Output during the Tour de France.
AB  - The aim of this study was to evaluate the demands of riding a "Grand Tour" by
      monitoring both heart rate and power output in 15 professional cyclists. SRM
      power output profiles (SRM Trainingsystem, Julich, Germany) were collected during
      148 mass start stages during the 2005 Tour de France and analyzed to establish
      average power, heart rate (HR) and cadence produced in different terrain
      categories (flat [FLT]; semi-mountainous [SMT]; mountainous [MT]). The maximal
      mean power (MMP) for progressively longer durations was quantified. Average HR
      was similar between FLT (133 +/- 10 bpm) and SMT (134 +/- 8 bpm) but higher
      during MT (140 +/- 3 bpm). Average power output revealed a similar trend (FLT 218
      +/- 21 W [3.1 +/- 0.3 W/kg], SMT 228 +/- 22 W [3.3 +/- 0.3 W/kg], and MT 234 +/-
      13 W [3.3 +/- 0.2 W/kg]). Cadence during MT was approximately 6 - 7 rpm lower (81
      +/- 15 rpm) compared to FLT or SMT. During MT stages, the MMP for 1800 sec. was
      highest (394 W vs. 342 W) but the MMP 15 was lower (836 W vs. 895 W) compared to
      FLT. The data document comprehensively the power output demands during the Tour
      de France.

PMID- 17497570
TI  - Differential reflex adaptations following sensorimotor and strength training in
      young elite athletes.
AB  - In young elite athletes the influence of a sensorimotor training (SMT = balance
      training) on strength, jump height and spinal reflex excitability was compared
      with adaptations induced by strength training (ST). Seventeen athletes were
      randomly assigned to either a SMT or a ST group. Before and after 6 weeks of
      training, maximal isometric strength (MVC) and rate of force development (RFD
      (max)) were determined. Changes in jump height and EMG activity were assessed
      during squat- (SJ), countermovement- (CMJ) and drop-jump (DJ). To evaluate neural
      adaptations, H-reflex recruitment was recorded at rest and during dynamic
      activation of the plantarflexors following stance perturbation. MVC was enhanced
      after ST but not influenced by SMT. RFD (max) was not affected by any training.
      Both SMT and ST significantly improved jump performance in SJ, CMJ, and DJ.
      Maximum H-reflex to maximum M-wave ratios (H (max)/M (max)-ratios) at rest
      remained unchanged. During stance perturbation, H (max)/M (max)-ratios were
      significantly reduced following SMT whereas ST augmented H (max)/M (max)-ratios
      (p < 0.05). In contrast to other studies, no changes in RFD were found. This may
      be explained by methodological and/or training specific differences. However,
      both SMT and ST improved jump performance in well trained young athletes but
      induced opposing adaptations of the H (max)/M (max)-ratio when measured during
      dynamic contractions. These adaptations were task-specific as indicated by the
      unchanged reflexes at rest. Decreased spinal excitability following SMT was
      interpreted as the attempt to improve movement control, whereas augmented
      excitability following ST accounts for the effort to enhance motoneuron output.
      Functionally, our results emphasise that SMT is not only beneficial for
      prevention and rehabilitation but also improves athletic performance.

PMID- 17497571
TI  - Reproducibility of a laboratory based 20-km time trial evaluation in competitive
      cyclists using the Velotron Pro ergometer.
AB  - The purpose of this study was to evaluate the reliability of a 20-km cycling time
      trial using the Velotron cycle ergometer in competitive cyclists. Twenty male
      cyclists (V.O (2max) = 68.5 +/- 3.6 ml . kg (-1) . min (-1); peak power (P
      (peak)) = 469 +/- 33 W) participated in this study. Each subject performed a V.O
      (2max) test and 3 separate 20-km time trials (TT1, TT2, and TT3). Data from
      trials were compared using a one-way ANOVA. Coefficients of variation (CV) and 95
      % confidence intervals (CI) were calculated between trials. Values are mean +/-
      SD unless otherwise noted. Performance time T (tot) (30.03 +/- 1.24, 30.12 +/-
      1.21, and 30.14 +/- 1.21 min) and mean absolute power (P (mean)) (326 +/- 35, 323
      +/- 35, 322 +/- 34 Watts) were not significantly different across TT1 - TT3. P
      (mean) was highly related between TT1 - TT2 (r = 0.96; p < 0.01) and TT2 - TT3 (r
      = 0.97; p < 0.01). A low CV was also demonstrated between trials for P (mean)
      (TT1 - TT2 = 2.1 %, CI = 1.6 % to 3.1 %; TT2 - TT3 = 1.9 %, CI = 1.4 % to 2.8 %).
      P (peak) and P (mean) were both correlated to T (tot) in TT1 with P (mean)
      accounting for most of the variance in T (tot) (R (2) = 0.993). These data show
      that performance in a 20-km time trial using the Velotron ergometer is highly
      reproducible in competitive cyclists. Furthermore, the CV variance demonstrated
      between trials is comparable to that expected during actual performance in elite
      athletes.

PMID- 17497572
TI  - Biomechanical analysis of the breaststroke start.
AB  - The aim of this study was to analyse the kinematics and coordination of the
      breaststroke start as regards to skill level using a video device. Ten national
      swimmers were compared with an international swimmer. All swimmers simulated the
      100-m pace for 25 m after a grab start. The kinematical analysis assessed the
      durations of leave block, flight, entry and glide, pull-out, and the swim up to
      the 15-m mark phases. The coordination analysis assessed the durations of the
      time spent with the arms close to the thighs after a complete arm pull-push, the
      time gap between the end of the arm recovery and the beginning of the leg
      propulsion during the pull-out phase and at the first swim stroke, and the time
      gap between the end of leg propulsion and the beginning of arm propulsion. The
      international swimmer had a shorter 15-m start time than the national swimmers
      due to shorter times in the swim phase, longer times in the underwater phase,
      longer times spent with the arms close to the thighs and in glide with the body
      in extension. The whole population showed a negative superposition of leg
      propulsion with arm recovery at the pull-out phase, which disappeared at the
      first swim stroke.

PMID- 17497573
TI  - Comparison of the decrease in strength between hamstrings and quadriceps during
      isokinetic fatigue testing in semiprofessional soccer players.
AB  - An imbalance in the agonist/antagonist ratio has been identified as a pathologic
      factor. Using an isokinetic dynamometer, several studies have investigated the
      loss of quadriceps strength due to fatigue, but few have explored this phenomenon
      in the hamstrings. This study assessed the decline in strength of the hamstring
      and quadriceps muscles with fatigue. The goal was to determine whether a
      divergence in the decline in strength occurs that would affect the hamstring to
      quadriceps ratio of endurance. Twenty-seven professional soccer players were
      selected for endurance testing to evaluate fatigue on an isokinetic dynamometer.
      The decline in hamstring strength was significantly greater than that of the
      quadriceps after 15 repetitions for the dominant leg and after 40 repetitions for
      the nondominant leg. This study also revealed a decline in the endurance ratio
      compared with the maximal strength ratio in the dominant leg after 30
      repetitions. In fatigue states, the decline in hamstring strength diverges from
      that of the quadriceps in both legs. This difference in resistance to fatigue
      provokes an imbalance that may affect the stabilizing function of the thigh
      muscles. These results can be considered as indicators of an increased risk of
      injury during exhausting effort.

PMID- 17497574
TI  - Neuroendocrine and psychological assessment in a guinness 10 days scuba dive.
AB  - This study was designed to evaluate physiological and psychological stress
      parameters in 2 professional trained scuba divers, using a unique
      physiopathologic model, offered by the guinness 240 hours scuba dive. Two scuba
      dive masters have spent 240 hours at 6 - 8 meters depth (26.4 ft) in Ponza Island
      water (Italy). Blood samples were collected daily in the underwater bell; samples
      were carried out of water in waterproof bags. Breath samples were collected,
      measuring ethylene release. Psychological assessment was performed using the
      State and Trait Anxiety Inventory and the Zung self-rating depression scale. In
      the studied subjects, cortisol and prolactin showed physiological pulsatile
      secretion. Breath ethylene didn't exceed normal values. At the start of the
      study, no subjects showed high levels of state anxiety, trait anxiety and current
      depression. Psychometric scales scores remained steady during the diving period
      and no subjects showed anxiety and/or depression and/or panic symptoms during the
      time of observation. The present study shows that, although the long-time diving,
      well trained professional divers did not develop anxiety and/or depression. No
      subject discontinued the diving due to occurred psychological disorders or
      systemic events. The present report shows that the long-term diving permanence is
      possible, at least in well trained scuba divers.

PMID- 17497575
TI  - Variation in top level soccer match performance.
AB  - This study examined the influence of the opposing team, seasonal variations and
      the influence of first half activity on match performance in top-level soccer
      players. Physical performance measures were collected using the ProZone match
      analysis system from 20 professional soccer players from the same team and their
      opponents (n = 188) during a season. Match activities (standing, walking,
      jogging, running, high-speed running and sprinting), distances (total distance
      [TD], high-intensity running [HIR] and very high-intensity running [VHIR]) and
      other measures including involvement with the ball and peak running speed were
      collected. The influence of opponent team, the level of opposition, first half
      physical activities on second half activities, and playing position were
      analysed. The main finding was that TD (r = 0.62, p < 0.05), HIR (r = 0.51, p <
      0.05), and VHIR (r = 0.65, p < 0.05) of the reference team was influenced by the
      activity profile of the opponent teams. The TD and HIR was higher against Best
      opponent teams compared to Worst opponent teams (p < 0.05), and the TD, HIR and
      VHIR travelled in the first half significantly influenced the distances covered
      in the second half. TD, HIR and VHIR were greater at the end of the season. These
      results may be used to interpret meaningful changes in match performance in top
      level soccer.

PMID- 17497576
TI  - Fatigue differences between adults and prepubertal males.
AB  - The purpose of the present study was to investigate the differences in
      neuromuscular activation of agonist and antagonist muscles between men and
      prepubertal boys during a maximal isokinetic fatigue test. Ten prepubertal boys
      (mean +/- SD age: 10.5 +/- 0.6 years) and fourteen adults (age: 24.3 +/- 2.5
      years) executed 25 consecutive maximal isokinetic knee extensions at 60 deg . s (
      1). Peak torque and the electromyogram (EMG) of the vastus lateralis, vastus
      medialis and biceps femoris muscles were recorded. During the fatigue protocol,
      the prepubertal boys were able to produce higher torque than the adults, when
      expressed as percent of their maximal value, indicating that adults were more
      fatigable. The agonist activity, especially for the vastus lateralis muscle,
      increased in both groups during the first 10 knee extensions, and then decreased
      more in adults. The antagonist activity of biceps femoris muscle in adults
      remained constant throughout the fatigue task, whereas the children showed, on
      average, an increased biceps femoris antagonistic activation, especially during
      the first 10 and last 5 knee extensions. These results suggest that adults are
      more fatigable than children during a maximal isokinetic fatigue protocol,
      probably due to an increased inhibition or reduced facilitation of their agonist
      drive.

PMID- 17497577
TI  - Does power indicate capacity? 30-s Wingate anaerobic test vs. maximal accumulated
      O2 deficit.
AB  - The purpose of this study was to evaluate the relationship between anaerobic
      power and capacity. Seven men and seven women performed a 30-s Wingate Anaerobic
      Test on a cycle ergometer to determine peak power, mean power, and the fatigue
      index. Subjects also cycled at a work rate predicted to elicit 120 % of peak
      oxygen uptake to exhaustion to determine the maximal accumulated O (2) deficit.
      Peak power and the maximal accumulated O (2) deficit were significantly
      correlated (r = 0.782, p = 0.001). However, when the absolute difference in
      exercise values between groups (men and women) was held constant using a partial
      correlation, the relationship diminished (r = 0.531, p = 0.062). In contrast, we
      observed a significant correlation between fatigue index and the maximal
      accumulated O (2) deficit when controlling for gender (r = - 0.597, p = 0.024)
      and the relationship remained significant when values were expressed relative to
      active muscle mass. A higher anaerobic power does not indicate a greater
      anaerobic capacity. Furthermore, we suggest that the ability to maintain power
      output during a 30-s cycle sprint is related to anaerobic capacity.

PMID- 17497578
TI  - Time at VO2max during intermittent treadmill running: test protocol dependent or
      methodological artefact?
AB  - Effects of methodological differences on the determination of time at VO (2max)
      (t (VO2max)) during intermittent treadmill running were investigated. Subjects
      performed three incremental tests to volitional exhaustion: a continuous protocol
      with 1-min stages (Cont-INC ([1-min])), and two discontinuous protocols of 2-min
      (Dis-INC ([2-min])) and 3-min (Dis-INC ([3-min])) stage durations. For each test,
      VO (2max) and the running velocity associated with V.O (2max) (vVO (2max)) were
      determined. On a fourth visit, subjects performed an intermittent test with 30-s
      work and relief intervals run at 105 % and 60 %, respectively, of the vV. (2max)
      determined during Cont-INC ((1-min)). The t (VO2max) during the intermittent test
      was determined using three different criteria: VO (2) data points > or = 100 % VO
      (2max) determined in Cont-INC ((1-min)) (t (VO2max[100 %])), > or = 95 % VO
      (2max) (t (VO2max[95 %])) and > or = VO (2max) minus 2.1 ml . kg (-1) . min (-1)
      (t (VO2max[- 2.1])). The V.O (2max) means (SD) for Cont-INC ((1-min)), Dis-INC
      ((2-min)) and Dis-INC ((3-min)) were 4093 (538), 4096 (516), and 3980 (488) mL .
      min (-1), respectively. The t (VO2max) means (SD) were: t (VO2max(100 %)) 163
      (227) s, t (VO2max(95 %)) 418 (439) s, and t (VO2max(- 2.1)) 358 (395) s. All
      differences in t (V.O2max) were significantly different (p < 0.05). Differences
      in t (VO2max) due to using V.O (2max) values derived from using different V.O (2)
      time-averages were significantly different (p < 0.05). Methodological differences
      should be considered during interpretation of previous studies.

PMID- 17497579
TI  - Motor abilities and aerobic fitness of obese children.
AB  - Obesity is considered to be epidemic worldwide. Stopping further progression
      interdisciplinary, outpatient intervention therapy programs for obese children
      have become increasingly important. FITOC (Freiburg Intervention Trial for Obese
      Children) consists of a combination of organized sports, behavioral therapy and
      nutritional advice. The effectiveness of the therapy is determined on the basis
      of anthropometrical and physical performance data. The purpose of this report is
      to give a differentiated view of the motor abilities of obese children and to
      describe changes in the course of the therapy program FITOC. Data were collected
      on n = 49 obese children (BMI > 97th percentile) aged 8 - 12 in a pretest at the
      beginning and posttest at the end of the intensive phase of the therapy. These
      data were compared with an age-matched German reference group. Besides the
      General Sports-Motor Test (Allgemeiner Sportmotorischer Test [AST]), the BMI-SDS
      values, the body fat mass (FM %) and the aerobic capacity (Watt/kg body weight)
      were recorded. In the pretest, the running exercise results and the aerobic
      capacity checked ranged significantly below the values of the reference group.
      The performance in the coordinative tests of the AST was differentiated. The
      medicine-ball toss was significantly above average of the reference group. In the
      posttest, the BMI-SDS values and the body fat mass (% FM) decreased (p < 0.001)
      and the aerobic capacity improved (p < 0.001). Performance in all motor abilities
      tests improved and the difference between the strength of the obese children and
      the strength of the reference group decreased. This study demonstrates that in
      obese children weight-bearing activities are below average but not all motor
      abilities.

PMID- 17497580
TI  - Differences in physical fitness and throwing velocity among elite and amateur
      female handball players.
AB  - This study compared physical characteristics (body height [BH], body mass [BM],
      body fat [BF], and fat free mass [FFM]), one repetition maximum bench press (1RM
      (BP)), jumping explosive power (VJ), handball throwing velocity, power-load
      relationship of the leg and arm extensor muscles, 5- and 15-m sprint running
      time, and running endurance in elite (n = 16; EF) and amateur (n = 15; AF) female
      handball players aged 17 - 38. Results revealed that, compared to AF, EF players
      presented similar values in body mass and percent body fat, but higher values (p
      < 0.001 - 0.05) in BH (6 %), FFM (10 %), 1RM (BP) (23 %), VJ (10 %), handball
      throwing velocity (11 %), power-load relationship of the arm (25 %) and leg (12
      %) extensors, as well as 5- and 15-m sprint (3 - 4 %) and endurance running
      velocities (13 %). Univariate regression analyses showed that 1RM (BP) was
      associated with throwing velocity (R (2) = 0.64). The higher absolute values of
      maximal strength and muscle power, although explained by the differences in fat
      free mass, will give EF an advantage to sustain certain handball game actions.
      The association between 1RM (BP) and throwing velocity suggests that throwing
      velocity values in female handball players depend more on maximal strength than
      on the capacity to move low loads at high velocities, during elbow extension
      actions.

PMID- 17497581
TI  - Functional eccentric-concentric ratio of knee extensors and flexors in pre
      pubertal children, teenagers and adult males and females.
AB  - The purpose of this study was to examine the age and sex associated differences
      in the eccentric/concentric functional ratio for the knee. Isokinetic concentric
      and eccentric knee extension and flexion was measured at 0.52 rad x s (-1) and
      3.14 rad x s (-1) in 121 subjects. Other than mass there were no significant age
      by-sex interaction effects for all variables examined. A significant velocity-by
      age group effect was demonstrated for ECC (KF)/CON (KE) with higher ratios at
      3.14 compared to 0.52 rad x s (-1). Females' CON (KF)/ECC (KE) was significantly
      lower than males at both velocities. Adults demonstrated significantly lower CON
      (KF)/ECC (KE) than the teenagers at 0.52 rad x s (-1) and lower than the
      prepubertal and teenager groups at 3.14 rad x s (-1). However, for ECC (KF)/CON
      (KE) at 3.14 rad x s (-1), prepubertal ratios were significantly lower than
      teenagers and adults. The results of the current study suggest that functional
      rather than conventional ratio should be used when examining knee stability.
      During fast velocity movements, prepubertal children have a lower capacity for
      generating eccentric compared to concentric torque. The lower CON (KF)/ECC (KE)
      ratio in adults appears to be due to a greater ability to generate large
      eccentric torques at all slow and fast movement velocities. The lower CON
      (KF)/ECC (KE) ratio in females is a product of lower concentric torque as opposed
      to high eccentric torque producing capability as previously thought.

PMID- 17497582
TI  - Efficacy of instability resistance training.
AB  - The use of the stability ball as a platform for upper-body resistance training
      has gained much attention in recent years. However, the efficacy of such training
      regimens remains largely unstudied. The purpose of this study was to evaluate the
      influence of platform (unstable vs. stable, stability ball vs. flat bench) on
      strength and work capacity during barbell chest-press exercise. We also sought to
      determine the effects of a barbell chest-press training program performed on a
      stability ball or flat bench on strength, work capacity, and abdominal power.
      Fourteen young women (20 - 23 yr) performed a 1 repetition maximum (1RM) barbell
      chest-press and the YMCA bench press test (YBT) on a stability ball and flat
      bench, as well as two field tests measuring abdominal power. The women were then
      assigned to perform 3 weeks of barbell chest-press training on a stability ball
      (SB group) or flat bench (FB group); assignment was balanced based on 1RM
      strength. Barbell chest-press training included 3 sets of 3 - 5 repetitions at
      loads greater or equal to 85 % of 1RM. The 1RM barbell chest-press, YBT, front
      abdominal power test (FAPT), and side abdominal power test (SAPT) were used to
      evaluate changes in strength, work capacity, and abdominal power, respectively.
      The chest-press tests were completed on both platforms following the training
      program. Platform (stability ball vs. flat bench) had no influence on strength,
      but work capacity was initially 12 % lower on the stability ball compared to the
      flat bench. In response to training, both groups significantly increased strength
      and work capacity, and there were no group differences. The increase in 1RM
      strength was 15 % and 16 % on the stability ball and flat bench for the SB group,
      and 16 % and 19 % for the FB group, respectively. The increase in work capacity
      was 32 % and 13 % on the stability ball and flat bench for the SB group, and 27 %
      and 26 % for the FB group, respectively. Both groups significantly improved on
      the FAPT, and there were no group differences. Performance on the FAPT improved
      by 5 % for the SB group, and 22 % for the FB group. Performance on the SAPT did
      not change. Barbell chest-press training performed on either the stability ball
      or flat bench increased strength and work capacity, and these changes were
      transferable across platforms. Thus, the stability ball is an effective platform
      for barbell chest-press training in untrained women over a short duration.

PMID- 17497583
TI  - Power output measurement during treadmill cycling.
AB  - The study aim was to consider the use of a motorised treadmill as a cycling
      ergometry system by assessing predicted and recorded power output values during
      treadmill cycling. Fourteen male cyclists completed repeated cycling trials on a
      motorised treadmill whilst riding their own bicycle fitted with a mobile
      ergometer. The speed, gradient and loading via an external pulley system were
      recorded during 20-s constant speed trials and used to estimate power output with
      an assumption about the contribution of rolling resistance. These values were
      then compared with mobile ergometer measurements. To assess the reliability of
      measured power output values, four repeated trials were conducted on each
      cyclist. During level cycling, the recorded power output was 257.2 +/- 99.3 W
      compared to the predicted power output of 258.2 +/- 99.9 W (p > 0.05). For graded
      cycling, there was no significant difference between measured and predicted power
      output, 268.8 +/- 109.8 W vs. 270.1 +/- 111.7 W, p > 0.05, SEE 1.2 %. The
      coefficient of variation for mobile ergometer power output measurements during
      repeated trials ranged from 1.5 % (95 % CI 1.2 - 2.0 %) to 1.8 % (95 % CI 1.5 -
      2.4 %). These results indicate that treadmill cycling can be used as an ergometry
      system to assess power output in cyclists with acceptable accuracy.

PMID- 17497584
TI  - Cardiovascular responses to static exercise: a re-appraisal.
AB  - Traditional findings of circulatory responses to a bout of static exercise
      include an abrupt rise in systolic and diastolic blood pressure, small increases
      in cardiac output with no rise in stroke volume, and unaltered systemic vascular
      resistance. These characteristics are not, however, consistent with current
      concepts of circulatory adjustments to high intramuscular pressure and inability
      of the heart to generate increases in cardiac output by heart rate alone. When
      circulatory responses to static exercise are in considered on a per-beat basis,
      at times of circulatory flow, these conflicts are resolved, as systemic vascular
      resistance is observed to rise, and augmentation of cardiac output can be
      accounted for by improvements in myocardial contractility.

PMID- 17497585
TI  - Carbohydrate effect: hormone and oxidative changes.
AB  - Carbohydrate administration during exercise diminishes stress hormone release,
      but the relationship of these hormones with oxidative stress has not been
      examined. Fifteen subjects functioned as their own controls and ingested
      carbohydrate (6 %) or placebo in a randomized design while cycling for 2.5-h (
      approximately 75 % V.O (2peak)). Blood and skeletal muscle samples were collected
      30 min pre-exercise, immediately post-exercise, and 12-h post-exercise and
      analyzed for F (2)-isoprostanes, ferric reducing ability of plasma, glucose,
      insulin, cortisol, epinephrine, and muscle glycogen, respectively. Statistical
      design was a 2 (treatment) x 3 (time) repeated measures analysis of variance.
      Glucose, insulin, and ferric reducing ability of plasma were significantly higher
      and F (2)-isoprostanes, cortisol, and epinephrine significantly lower in
      carbohydrate versus placebo. The decrease in muscle glycogen was not different.
      During cycling exercise, oxidative stress appears to be heavily influenced by
      carbohydrate ingestion and increased stress hormones.

PMID- 17497586
TI  - Ventilatory and lactic thresholds in subjects with sickle cell trait.
AB  - This study investigated 1) whether ventilatory and lactic thresholds (VT and LT,
      respectively) are different in sickle cell trait carriers (SCTc) and subjects
      with normal hemoglobin (control group), and 2) whether the first LT and VT and
      the second LT and VT are respectively coincident in the two populations. Seven
      SCTc and 8 control subjects performed an incremental exercise test (IET). Blood
      lactate concentration and cardioventilatory variables were analyzed at rest and
      during IET. No significant difference in the ventilatory parameters (notably,
      maximal oxygen uptake [VO (2max)] and the ventilatory thresholds) or the lactic
      thresholds was observed between the two groups. In both SCTc and control
      subjects, the LTs and VTs did not occur at the same exercise intensity. The first
      VT did not coincide with the first LT, in contrast with the second VT and the
      second LT, which coincided in both groups. In conclusion, SCTc exhibited normal
      ventilatory and lactic responses during a progressive and maximal exercise test
      assessing aerobic physical fitness.

PMID- 17497587
TI  - Does k-11706 enhance performance and why?
AB  - Erythropoietin gene expression is stimulated by hypoxia-inducible factor 1 and
      inhibited by GATA. Thus, drugs that attenuate the action of GATA and/or
      potentiate the action of HIF-1 may increase Epo production and hemoglobin
      concentration. The effects of such drugs on endurance performance and the
      potential mechanisms by which they may exert effects are unclear. In Hep3B cells,
      we showed that K-11706 inhibits GATA binding activity, but enhances HIF-1 binding
      activity. However, the expression levels of GATA and HIF-1 protein were not
      changed by the addition of K-11706. We investigated the effects of K-11706 on Epo
      and Hb concentrations, hematocrit and endurance performance of mice (total number
      of mice = 40). K-11706 was dissolved in polyethylene glycol and administered via
      oral tube feeding to mice for either five or eight days. Endurance performance
      was assessed using a treadmill. Muscle fibers from the quadriceps muscles of mice
      were stained with ATPase. Administration of 3 mg/kg K-11706 for five or eight
      days significantly increased erythropoietin concentrations, hemoglobin
      concentrations, hematocrit and endurance performance, but the diameters of cross
      sections and ratios of type I, IIA and IIB muscle fibers were not affected.

PMID- 17497588
TI  - Do non-steroidal anti-inflammatory drugs influence the steroid hormone milieu in
      male athletes?
AB  - Prostaglandins modulate the hypothalamus-pituitary-adrenal and -gonadal axis
      pathways. We explored the effects of a single course of treatment with
      acetylsalicylic acid (ASA), an inhibitor of prostaglandin synthesis, on the
      steroid milieu in athletes. Morning plasma cortisol (F), dehydroepiandrosterone
      sulphate, free-testosterone, testosterone (T) and their ratios were evaluated
      before and after the administration of either ASA or placebo in twelve male
      athletes, when affected by minor musculoskeletal trauma and, as control, after a
      five/six week wash-out in healthy conditions respectively. One tablet of ASA (800
      mg), or placebo, was administered two times daily for 10 days during treatment.
      All the volunteers suspended exercise training during treatment. The results
      revealed that compared to placebo, plasma F was significantly lower after ASA
      treatment (p = 0.023). Furthermore, the comparison of hormone's absolute and
      percentage of variations (Delta and Delta%) between ASA and placebo treatment
      showed significant differences respectively for DeltaF (p = 0.045), for DeltaT (p
      = 0.047), for DeltaT/F (p = 0.042), for DeltaF% (p = 0.04) and for DeltaT% (p =
      0.049). Our data suggest that in comparison to placebo, a short-term ASA
      treatment is able to influence the plasma steroid milieu in athletes. Due to the
      observed variability of the individual hormonal patterns, further research is
      required to substantiate these findings.

PMID- 17497589
TI  - Postoperative programmed muscle tension augmented osteotendinous junction repair.
AB  - The postoperative programmed muscle tension induced by functional electrical
      stimulation (FES) was evaluated for its potential efficacy on acceleration of
      osteotendinous junction healing using an established partial patellectomy model
      in rabbits. After immobilization of the operated knee for 6 weeks, daily FES was
      applied to quadriceps muscles for 30 minutes per day and 5 days per week for 6
      weeks in the treatment group and compared with the non-treatment control group at
      postoperative week 12 and 18, radiologically, histologically and biomechanically.
      Results showed that FES-induced muscle tension significantly increased new bone
      formation, bone mineral density, and fibrocartilage zone restoration in the
      osteotendinous healing interface. The failure load and ultimate strength of the
      repairing osteotendinous complex were also improved significantly with healing
      over time. In conclusion, the postoperative programmed FES-induced muscle tension
      was favorable for acceleration of osteotendinous junction repair and therefore
      recommended for clinical trails in orthopedic sports medicine and rehabilitation.

PMID- 17497590
TI  - Unusual fracture of the humerus in a volleyball player: a case report.
AB  - We describe a case of a female high school volleyball player who suffered a
      humeral shaft fracture while executing a floater serve. Based on the patient's
      history, a stress fracture was initially suspected. However, plain radiographs
      showed no periosteal reactions, callus formation or osteosclerosis, and thus we
      could not make a definite diagnosis of "stress fracture". It is suggested that an
      instantaneous muscle force in addition to rotational forces applied by impact
      with the ball caused the fracture. Her fracture healed without any subsequent
      disabilities based on a conservative medical management with a plaster splint,
      and she returned to the volleyball team. The inaccuracy of her serve form in
      addition to her own muscular force might be involved in the mechanism of injury.
      Instruction on achieving appropriate serve form might help prevent such
      fractures.

PMID- 17497591
TI  - Effects of a supplementation during exercise and recovery.
AB  - The present study was designed to investigate whether a protein hydrolysate
      enriched in branched chain amino acids and antioxidants, trace and mineral
      elements, and vitamins would affect performance and fatigue. Eighteen sportsmen
      underwent testing before and after 28 days supplementation with either treatment
      in protein hydrolysate or placebo. Testing included exhaustive aerobic and
      anaerobic exercises with determination of blood lactate concentration through
      exercise and recovery and antioxidant status, but also measurements of maximal
      oxidative capacity (V. (max)) and citrate synthase activity (CS) from a resting
      muscle biopsy. Protein hydrolysate resulted in a significant decrease in fatigue
      indices, without affecting performances. A significant increase in enzymatic
      antioxidant and a decrease in oxidative damage were observed at rest after
      treatment but not with a placebo. Decrease in maximal blood lactate and
      improvement of blood lactate removal were only observed after protein hydrolysate
      treatment. Furthermore, CS increased significantly, whereas no change was
      observed in V. (max). In conclusion, this protein hydrolysate treatment induced
      adaptations that may promote a decrease in fatigue during exercises, potentially
      explained by changes in parameters used to represent oxidative damage and
      antioxidant status at rest and changes in lactate metabolism.

PMID- 17497592
TI  - Dietary intake, serum hormones, muscle mass and strength during strength training
      in 49 - 73-year-old men.
AB  - Effects of dietary intake on serum hormones, muscle cross-sectional area (CSA)
      and strength during strength training were studied in two groups of men: 1)
      strength training + nutritional counseling (n = 22, 59.1 +/- 6.1 yrs), and 2)
      strength training (n = 23, 58.5 +/- 7.1 yrs). Both groups performed strength
      training twice a week for 21 weeks. Counseling increased carbohydrate (p < 0.01)
      and fiber intake (p < 0.001) and polyunsaturated/saturated fat-ratio (p < 0.05)
      and decreased fat intake (p < 0.01). Muscle strength and CSA increased by 16 - 20
      % and by 5.4 - 5.9 % in both groups (p < 0.001). Changes in protein content of
      diet correlated with the changes in the acute postexercise concentrations of
      total (r = 0.64, p < 0.01) and free testosterone (r = 0.54, p < 0.05) after
      training in the counseling group. Moreover, changes in the free testosterone
      responses to heavy-resistance exercise correlated with the increases in the
      muscle CSA (r = 0.52, p < 0.05) in the counseling group. Serum basal
      testosterone/sex hormone-binding globulin-ratios correlated with the body mass
      normalized energy (kJ/kg: r = 0.54, p < 0.001), protein (g/kg: r = 0.42, p <
      0.01) and fat (g/kg: r = 0.51, p < 0.01) intake in all participants during the
      training. The data indicate that protein and fat intake may influence serum
      testosterone concentrations and that the changes in exercise-induced testosterone
      responses may contribute to muscle mass development during strength training.

PMID- 17497593
TI  - Branched-chain amino acids and arginine supplementation attenuates skeletal
      muscle proteolysis induced by moderate exercise in young individuals.
AB  - This study aimed at evaluating the effect of a single oral intake of branched
      chain amino acids (BCAA) with Arg on skeletal muscle protein metabolism during
      moderate exercise in young individuals. Eight healthy volunteers (4 males and 4
      females, means +/- SEM, 26 +/- 1 yrs, 177.8 +/- 3.7 cm, 72.6 +/- 3.9 kg) were
      studied in a randomized double-blind placebo-controlled cross-over trial. The
      subjects performed 3 bouts of 20-min cycling exercise (5-min break between each
      bout) at 126 +/- 13 W corresponding to 50 % of the maximal work intensity. A
      single oral supplement of either a BCAA drink containing 2 g of BCAA and 0.5 g of
      Arg or an isocaloric placebo drink was given at 10 min of the 1st exercise bout.
      Both arterial and venous blood samples were simultaneously taken from the radial
      artery and the femoral vein, respectively. Blood flow in the femoral artery was
      determined using the ultrasound Doppler technique. The blood sampling and blood
      flow measurements were performed at rest, every 10 min during each exercise bout.
      Net balance of BCAA and Phe across the leg muscles were measured by the
      arteriovenous difference method. The BCAA ingestion resulted in increases in both
      the plasma BCAA concentration and BCAA uptake into the working leg. The Phe
      release from the leg during exercise significantly increased as compared to the
      basal level in the placebo trial (0.97 +/- 0.28 vs. 0.23 +/- 0.22 micromol/min, p
      < 0.05). In the BCAA trial, the cumulative Phe release from the leg during the
      3rd exercise bout was significantly lower than that in the placebo trial (5.0 +/-
      7.4 vs. 35.9 +/- 13.2 micromol/25 min, p < 0.05). These results suggest that
      endurance exercise at moderate intensity enhances proteolysis in working muscles,
      and a single oral intake of 2 g of BCAA with Arg at onset of exercise effectively
      suppresses exercise-induced skeletal muscle proteolysis.

PMID- 17497594
TI  - Relationship between TFAM gene polymorphisms and endurance capacity in response
      to training.
AB  - The aim of this study was to explore whether polymorphisms in mitochondrial
      transcription factor A ( TFAM) gene are associated with endurance capacity in a
      pretraining state (baseline) and/or in response to a supervised 18-wk endurance
      training (changes) in 102 young Chinese males (nonathletes). Phenotypes measured
      were running economy (RE) and V(.)O (2max). Genomic DNA was extracted from white
      blood cells and the genotypes were analyzed by PCR-RFLP in single nucleotide
      polymorphisms (SNP) rs1937, rs2306604 and rs1049432. Genotype distributions were
      in Hardy-Weinberg equilibrium at three loci (p > 0.05). When the three
      polymorphisms were considered together, three haplotypes were estimated, i.e., G
      (rs1937)-A (rs2306604)-G (rs1049432) (49 %), G (rs1937)-G (rs2306604)-G
      (rs1049432) (33 %) and C (rs1937)-G (rs2306604)-T (rs1049432) (18 %). SNPrs1937
      and rs1049432 achieved near complete linkage disequilibrium (LD) (D' = 1 and r
      (2) = 0.903). We found no significant differences in baseline levels of V(.)O
      (2max) and RE between TFAM genotypes or haplotypes. Similarly, we found no
      differences for the training-induced changes of both variables. It was concluded
      that the three polymorphisms in TFAM gene rs1937, rs2306604 and rs1049432 do not
      predict endurance capacity/trainability, at least in Chinese males.

PMID- 17497595
TI  - Sutureless tension-free hernia repair with human fibrin glue (tissucol) in soccer
      players with chronic inguinal pain: initial experience.
AB  - Chronic groin pain is a common symptom experienced by soccer players, resulting
      in many athletes undergoing prolonged periods of conservative treatment. In a
      high proportion of these cases, however, the cause of groin pain is due to
      impalpable hernias, thus nullifying the usefulness of a conservative approach. Of
      the current surgical procedures for inguinal hernia repair, the Lichtenstein
      technique is widely used. The present study aims to evaluate the efficacy of mesh
      fixation with human fibrin glue (Tissucol) in open, tension-free inguinal repair,
      in the treatment of soccer players with groin hernia. A sutureless Lichtenstein
      technique was employed in 16 consecutive soccer players with primary groin
      hernia. Inguinal nerves were prepared and preserved. Human fibrin glue was used
      for mesh fixation, in place of conventional sutures. Results were rated as
      excellent in all cases, with no reported intra- or postoperative complications.
      All patients were discharged 4 - 5 h after the operation, and all returned to
      full pre-injury level sporting-activity, on average, 31 days (range 24 - 42 days)
      post surgery. This study confirms the efficacy of sutureless tension-free hernia
      repair with human fibrin glue for the treatment of soccer players suffering from
      chronic groin pain due to impalpable groin hernia.

PMID- 17497596
TI  - Physical activity and nutrition knowledge and preferences in kindergarten
      children.
AB  - The aim of the present study was to determine physical activity and nutritional
      knowledge and preferences in kindergarten children. Following height and weight
      measurement, and age and gender adjusted BMI percentile calculation, 202
      kindergarten children (4 - 6.5 yr) completed twice in a random order, a photo
      pair food and exercise questionnaire. Knowledge was determined by asking the
      child to choose food/activity that would make a selected doll healthier, while
      preferences where determined by the child's own choise. Nutritional knowledge
      score was higher than the physical activity knowledge score (73.4 +/- 1.5 vs.
      67.5 +/- 1.9 %, p < 0.006), while the nutrition preference score was lower than
      the physical activity preference score (42.2 +/- 1. 8 vs. 66.5 +/- 1.6 %, p <
      0.0001). There was a difference between nutrition knowledge and preferences (73.4
      +/- 1.5 vs. 42.2 +/- 1.8 %, p < 0.0001). No differences were found between
      physical activity knowledge and preferences. No differences were found between
      overweight and normal weight kindergartners. Female kindergartners had higher
      nutrition knowledge and preference scores, but lower physical activity preference
      scores compared to male kindergartners. Our data suggest that in developing
      health promotion programs for kindergarten children, an effort should be made to
      increase physical activity knowledge and to improve nutritional preferences.

PMID- 17497597
TI  - [Nephrogenic systemic fibrosis after application of gadolinium-based contrast
      agents--a status paper].
AB  - Recently the association of a rare disease named "nephrogenic systemic fibrosis"
      (NSF) with the administration of gadolinium-containing contrast media, especially
      gadodiamide (Omniscan, GE-Healthcare), was described. NSF is a scleroderma-like
      disease characterised by widespread tissue fibrosis. Until now, NSF cases were
      observed only in patients with kidney disease. Almost all patients were suffering
      from chronic renal insufficiency, 90 % of them required renal replacement
      therapy. The true incidence of the disease is unknown. First retrospective
      analyses of selected collectives of patients with end-stage renal disease showed
      2-5 % cases of NSF after administration of Gadolinium-containing contrast agents
      with an odds ratio of 20-50 in comparison to non-exposed controls. NSF is a
      serious adverse reaction, which may result in severe disabilities and even death.
      Therefore all radiologists applying gadolinium-based contrast agents should be
      informed about this disease and the recent recommendations for its prevention. On
      the basis of the published data, Omniscan should not be used in patients with
      severe renal impairment (GFR < 30 ml/min/1.73 m(2)) and those who have had or are
      undergoing liver transplantation. In neonates and infants up to 1 year of age,
      Omniscan should only be used after careful consideration. Also the other
      gadolinium-based contrast agents should be used in high-risk patients only after
      careful consideration using the lowest dose possible.

PMID- 17497598
TI  - Is it Really a Useful Index for Monitoring Training Follow-Up?

PMID- 17497599
TI  - The International Cycling Union unveils new anti-doping program. How much is
      enough?

PMID- 17497600
TI  - [Asymmetrical hearing loss following symmetrical acute acoustic trauma].
AB  - Due to diffraction, acute acoustic trauma usually causes symmetrical hearing
      loss. Acoustical shadow effects are relevant only at distances greater than 1 m
      to the sound source and frequencies greater than 1000 Hz. In case of pronounced
      asymmetrical hearing loss causal connection to acute acoustic trauma is unlikely.
      We describe two cases with pronounced asymmetrical hearing loss in spite of
      symmetrical acute acoustic trauma. In the first case two patients headed an
      exploding giant tyre in a distance of approximately 1-2 m. One of them--as
      expected--got a symmetrical inner ear damage. On the other hand the other
      patient, which stayed directly besides him, got a pronounced asymmetrical inner
      ear damage. In an additional case we found also asymmetrical inner ear damage
      after symmetrical noise exposure. In this case it was detected, that years ago
      the patient suffered from a menieriform attack in the now worse ear. Occult inner
      ear damage is discussed as a reason for the phenomenon of pronounced asymmetrical
      inner ear damage after symmetrical noise exposure.

PMID- 17497601
TI  - [Influence of European regulations on quality, safety and availability of cell
      and tissue allografts in Germany].
AB  - The transplantation of allogenic tissue (bone, cartilage, tendon, skin, amnion
      and special preparations such as demineralised bone matrix and acellular dermis)
      is an important component of the treatment of bone and soft tissue defects,
      particularly in traumatology and orthopaedic, reconstructive and plastic surgery.
      In Germany, the requirement for such tissue transplants is met by supply from
      local tissue banks (in particular bone banks) and a small number of regional and
      national tissue banks. These banks operate on the basis of the "Guidelines for
      Bone Banks" laid down by the German Chamber of Physicians, and of the German Drug
      Law (AMG). The 2004/23/EG guidelines issued by the European Parliament and
      ratified on 31/3/2004 define the quality and safety standards for the donation,
      procurement, testing, processing, preservation, storage and distribution of human
      tissues and cells. These guidelines will have a major impact on all aspects of
      tissue banking and transplantation. In particular, the new guidelines will remove
      the possibility for local tissue banks to operate outside of national drug laws (
      section sign 4 a [4]). The currently in draft law on "Quality and Safety of Human
      Tissues and Cells" ("Tissue Law") of the Federal Health Ministry seems to be
      heading in this direction, but it also includes possibilities for the
      continuation of local banks. An additional European guideline draft "Proposal for
      the regulation of advanced therapeutic medical products" is currently under
      discussion. This paper assesses the impact of these new pieces of legislation on
      the quality, safety and availability of human cell and tissue transplants in
      terms of the current situation and future prospects in Germany.

PMID- 17497602
TI  - [Commentary on the article of A. Pruss and R. von Versen: Influence of European
      regulations on quality, safety and availability of cell and tissue allografts in
      Germany].

PMID- 17497603
TI  - [Vermilion reconstruction after dog bite injuries].
AB  - Dog bite injuries often concern the lips. In children, injuries of the face are
      most common, but also in adults so-called kissing injuries frequently happen. All
      layer defects are treated by wedge excision in minor cases and by myocutaneous
      flaps in major cases of lower lip injuries, whereas upper lip defects are
      reconstructed by exchange flaps. If only the vermilion is concerned, mucosal
      flaps according to the von Esmarch technique yield very good aesthetic results
      with excellent function and without impairment of the mouth opening.

PMID- 17497604
TI  - [Epidemiology of auricular trauma].
AB  - BACKGROUND: Auricular trauma is rare but can seriously reduce self-acceptance and
      function. Epidemiologic data on the causes of trauma causes and patient
      characteristics are limited. PATIENTS AND METHODS: The case notes of 141 from 197
      patients with ear injuries have been reviewed retrospectively according to trauma
      cause and to the distribution of age and gender. RESULTS: Two thirds of the
      documented cases occurred between the age of 11 and 40 years. Men outnumbered
      women at a ratio of 2 to 1. The most frequent causes for ear trauma were traffic
      accidents (43 %), accidents at home (33 %), and fights (14 %). CONCLUSIONS:
      Mainly younger and active groups of the population are affected by ear trauma.
      Therefore, it is of particular concern in the acute setting to select those
      therapeutic options that have turned out good aesthetic and functional results in
      the long-term perspective.

PMID- 17497605
TI  - [Hirudo medicinalis-leech applications in plastic and reconstructive microsurgery
      -a literature review].
AB  - Medical leech therapy has enjoyed a renaissance in the world of reconstructive
      microsurgery during recent years. Especially venous congestion is decreased using
      hirudo medicinalis application such as following replantation of amputated
      fingers or congested flaps. They provide a temporary relief to venous engorgement
      whilst venous drainage is re-established. Living in symbiosis with Aeromonas
      hydrophila, who can digest the sixfold blood meal related to their body weight,
      and a broad number of anticoagulant agents such as the thrombin inhibitor
      hirudin, apyrase as well as collagenase, hyaluronidase, Factor Xa inhibitor and
      fibrinase I and II, leeches decrease venous congestion. Laser Doppler flowmetry
      could demonstrate a significant increase in superficial skin perfusion following
      leech application 16 mm around the biting zone. Following the initial blood meal
      accounting for about 2.5 ml, the anticoagulant effect of the various leeches
      enzymes follows within the next 5-6 hours, which both account for the beneficial
      effects. Infection associated with leech therapy is a documented complication of
      leech application, with reported incidences ranging from 2.4 to 20 % and a
      chinolone antibiotic is currently recommended to face the potential Aeromonas
      hydrophila infection. Anemia is a second adverse effect during medicinal leech
      application which has to be taken account with repetitive blood samples. Besides
      the successful applications of leeches in various applications in plastic and
      reconstructive microsurgery, randomized-controlled trials are pending to
      elucidate the value of hirudo medicinalis according to evidence-based criteria
      above from case series and case studies.

PMID- 17497606
TI  - [Infection with Aeromonas hydrophila after use of leeches (Hirudo medicinalis) in
      a free microvascular osteo-(myo-)cutaneous flap--suggestions for successful
      management].
AB  - Medical leeches (Hirudo medicinalis) are an important therapeutic option in the
      treatment of venous congestion of flaps. In a case report an infection with
      Aeromonas hydrophila of a free microvascular osteo-(myo)-cutaneous flap after
      leech application for venous congestion is described and the current literature
      reviewed. Infection associated with leech therapy is a documented complication of
      leech application, with reported incidences ranging from 2.4 to 20 %. In some
      cases an infection of the wound developed with Aeromonas hydrophila, a Gram
      negative rod that lives symbiotically in the intestines of the leech. Because of
      the risk of graft loss, early diagnosis and immediate initiation of an empirical
      intravenous antibiotic therapy with Piperacillin/Tacobactam or a third or fourth
      generation cephalosporins are essential even before results for sensitivity
      testing are received. An alternative is a short-term preemptive therapy with
      Cotrimoxazol or Ciprofloxacin during leech application.

PMID- 17497607
TI  - [Septic arthritis of the wrist].
AB  - BACKGROUND: Septic arthritis of the wrist is correlated with a high morbidity. To
      show diagnostic and therapeutic options we reviewed the patients treated with
      wrist infections at our institution for one year. METHODS: The data of ten
      patients who were treated for septic arthritis of the wrist in 2003 and 2004 were
      collected in a retrospective survey. Etiology, risk factors, microorganism and
      resistance data were recorded. RESULTS: Six infections were of an iatrogenic
      nature (four following surgery, one joint puncture and one joint injection). In
      nine cases there was a single arthritis of the wrist. One patient had
      oligoarthritis. In four cases Staphylococcus aureus, in one Proteus mirabilis and
      in one Pseudomonas aeroginosa were identified. In four cases, no microorganism
      could be identified. Two of the patients suffered from diabetes mellitus, one had
      rheumatoid arthritis. There was no significant elevation in the white blood cell
      count with 9.2 (4.5 - 12.5) x 10 (9)/L. Arthroscopic debridement and
      synovialectomy could be performed in one case. In the other cases open surgery
      was necessary. In four cases partial bone resection was required. Local
      antibiotics were installed in eight cases. All infections healed. In nine
      patients the joint was immobilized with an external fixation device. All patients
      received systemic antibiotics. Four wrists ended in an arthrodesis, one in a four
      corner fusion. On average, two (1 - 6) surgical interventions were necessary per
      patient. The six patients without an arthrodesis had a range of motion in
      extension/flexion of 30-0-24 degrees. CONCLUSION: Surgical treatment is
      sufficient in septic arthritis of the wrist. However, an early diagnosis and
      therapeutic intervention are essential to avoid a permanent disability.

PMID- 17497608
TI  - [Septic arthritis of finger joints].
AB  - BACKGROUND AND PURPOSE: Septic arthritis of finger joints is rare and its
      management not standardized. The outcome of all consecutive patients with finger
      joint arthritis was analyzed in terms of risk factors, surgical technique,
      antimicrobial therapy and hand therapy. PATIENTS AND METHODS: Data of 31 patients
      with surgical treatment between 1993 and 2005 were screened and those from 29
      patients with > 1 year of follow-up were retrospectively analyzed. Surgical
      techniques were debridement, primary, secondary arthrodesis or temporary joint
      distraction with external fixation. In addition, all patients were treated with
      antibiotics and hand physiotherapy. The median follow-up of the 29 patients was
      5.7 years. RESULTS: The most frequent cause was work injury (19/29), the leading
      causing agent Staphylococcus aureus (9/29). Overall 16/29 (55 %) of the patients
      with follow-up had a good result regarding healing of infection, lack of pain and
      fair function. Primary arthrodesis was performed in 3, secondary arthrodesis in 4
      patients. 3 patients were treated with temporary external fixation for three
      weeks. Cartilage damage detected during surgery (p = 0.01) was the significant
      risk factor for a bad outcome. The median delay to treatment was 4 days (1 - 550
      days). Antibiotics were given for a median of 2 days by the iv-route and 17 days
      orally. CONCLUSIONS: Septic arthritis of finger joints should be early recognized
      and immediately treated with surgery and antibiotics, in order to avoid cartilage
      damage. If cartilage is already damaged, primary arthrodesis with the use of an
      external fixation is indicated.

PMID- 17497609
TI  - [Hand infections resulting from underestimation of minimal injuries].
AB  - Frequently, the timely onset of adequate treatment is delayed when a hand
      infection is the result of minor trauma. The patients as well as the physicians
      are tempted to underestimate this complication. To prove that certain forms of
      trauma correlate with the degree of underestimation, we have prospectively
      studied the cases of 105 patients who required hospitalisation and surgical
      interventions between 2001 and 2003. We defined a cut-off point at 48 hours
      following trauma and differentiated between patients who appeared within this
      period from those who came later. Lesions at the fingertips, superficial and
      punctual injuries were more frequent among patients belonging to the group with
      the longer delay of treatment onset. Also pain was more intense and swelling of
      axillary lymph nodes was seen in this group more often. Patients who had been
      treated elsewhere before, were commonly found in this group as well. Patients who
      came within 48 hours following trauma required less surgical procedures. Also
      hospitalisation was shorter. Using a discriminant analysis, we calculated a
      linear equation to calculate a score, which helps to assess the individual degree
      of underestimation. This scoring system can help to identify patients who would
      benefit from early surgical treatment of the hand.

PMID- 17497610
TI  - [Manifestations of scleroderma at the hand--options for hand surgery in an
      interdisciplinary concept].
AB  - Clinical manifestations of scleroderma at the hand include Raynaud's phenomenon,
      calcinosis cutis, sclerodactylia and teleangiectasia. With the progression of the
      disease, cutaneous and joint contractions, acro-osteolysis, necrosis of the
      finger tips, and even extensive digital ulceration are likely to occur. These
      painful and often rapidly advancing lesions cause loss of function and
      disfigurement and, untreated, often lead to mutilation of the affected hand. Only
      an interdisciplinary management including the hand surgeon, the rheumatologist,
      and the physiotherapist can guarantee optimal treatment. Drug therapy should be
      included as well as physical therapy. Both should be made use of before and
      accompanying surgical treatment. Surgical therapy consists of treatment of the
      infections, excision of calcinosis, arthrodesis, in particular of the proximal
      interphalangeal joints, and sympathectomy. Amputation remains a final option,
      whereas with timely and sufficient treatment, amputations can be avoided and an
      improvement of function and an alleviation of the symptoms can be achieved. Among
      the non-operative treatment options, behavioural training, calcium antagonists,
      prostacyclin derivatives, topical nitrates as well as plexus anesthesia and
      stellatum blocks have proved to be effective. Recent drug therapies include
      endothelin-receptor antagonists for the prevention of digital ulceration and
      phosphodiesterase-V antagonists in treatment of Raynaud's phenomenon and
      induction of ulcer healing. With reference to several cases seen at our
      institution, we propose an interdisciplinary treatment concept for acral
      manifestations of scleroderma.

PMID- 17497611
TI  - [Correction of finger clubbing in primary hypertrophic osteoarthropathy (Touraine
      Solente-Gole syndrome)].
AB  - Finger clubbing can be a single physical finding. In Touraine-Solente-Gole
      syndrome, the primary form of hypertrophic osteoarthropathy, it is mostly
      associated with bone pain, hyperhydrosis, pachydermy and wrinkling of the
      forehead. In other cases, the presence of clubbing is associated with neoplastic,
      pulmonary, cardiac or other diseases and is then called Bamberger-Pierre-Marie
      syndrome, the secondary type of hypertrophic osteoarthropathy. The patient's
      history and careful physical examination, sometimes accompanied by laboratory and
      imaging studies, leads to the diagnosis. A patient with hereditary hypertrophic
      osteoarthropathy and its clinical symptoms is presented. Surgical correction of
      the clubbing fingers is demonstrated in the paper with bilateral resection and
      shortening of the nail bed, nail matrix and resection of soft tissue. Clubbing
      fingers are rare, but they might be part of a syndrome or a symptom of other
      diseases. Reconstructive surgery for aesthetic reasons can be performed.

PMID- 17497612
TI  - Weighted nonparametric maximum likelihood estimate of a mixing distribution in
      nonrandomized clinical trials.
AB  - Hierarchical models have a variety of applications, including multi-center
      clinical trials, local estimation of disease rates, longitudinal studies, risk
      assessment, and meta-analysis. In a hierarchical model, observations are sampled
      conditional on individual unit-specific parameters and these parameters are
      sampled from a mixing distribution. In observational studies or nonrandomized
      clinical trails, observations may be biased samples from a population and
      heterogeneous with respect to some confounding factors. Without controlling the
      heterogeneity in the sample, the standard estimation of the mixing distribution
      may lead to inaccurate statistical inferences. In this article, we propose a
      weighted nonparametric maximum likelihood estimate (NPMLE) of the mixing
      distribution and its smoothed version via weighted smoothing by roughening. The
      proposed estimator reduces bias by assigning a weight to each subject in the
      sample. The weighted NPMLE is shown to be weighted self-consistent and therefore
      can be easily calculated through a recursive approach. Simulation studies were
      conducted to evaluate the performance of the proposed estimator. We applied this
      method to clinical trial data evaluating a new treatment for stress urinary
      incontinence.

PMID- 17497613
TI  - Correctors of protein trafficking defects identified by a novel high-throughput
      screening assay.
AB  - High-throughput small-molecule screens hold great promise for identifying
      compounds with potential therapeutic value in the treatment of protein
      trafficking diseases such as cystic fibrosis (CF) and nephrogenic diabetes
      insipidus (NDI). The approach usually involves expressing the mutant form of the
      gene in cells and assaying function in a multiwell format when cells are exposed
      to libraries of compounds. Although such functional assays are useful, they do
      not directly test the ability of a compound to correct defective trafficking of
      the protein. To address this we have developed a novel corrector-screening assay
      for CF, in which the appearance of the mutant protein at the cell surface is
      measured. We used this assay to screen a library of 2000 compounds and have
      isolated several classes of trafficking correctors that had not previously been
      identified. This novel screening approach to protein-trafficking diseases is
      robust and general, and could enable the selection of molecules that could be
      translated rapidly to a clinical setting.

PMID- 17497614
TI  - An activity, stability and selectivity comparison of propioin synthesis by
      thiamine diphosphate-dependent enzymes in a solid/gas bioreactor.
AB  - Enzymatic carboligation in a solid/gas bioreactor represents a new challenge in
      biotechnology. In this paper, the continuous gas-phase production of propioin
      from two propanal molecules by using thiamine diphosphate-dependent enzymes was
      studied. Two enzymes were used, namely benzaldehyde lyase (BAL) from Pseudomonas
      fluorescens and benzoylformate decarboxylase (BFD) from Pseudomonas putida. The
      enzymes are homologous and catalyze carboligase and carbolyase reactions in which
      no external cofactor regeneration is needed. The influence of water and substrate
      activity on the initial reaction rate and biocatalyst stability was investigated.
      An increase in water activity raised the initial reaction rates to the maximal
      values of 250 and 80 U g(-1) for BAL and BFD, respectively. The half-life showed
      the same trend with maximal values of 50 and 78 min for BAL and BFD,
      respectively. The increase in the half-life by increasing water activity was
      unexpected. It was also observed that BFD is more stable than BAL in the presence
      of the substrate propanal. Both enzymes showed substrate inhibition in the
      kinetic studies, and BAL was also deactivated during the reaction. Unexpectedly,
      the stereoselectivity of both enzymes (ee of 19 % for BAL and racemic mixture for
      BFD) was significantly impaired in the gas phase compared to the liquid phase.

PMID- 17497615
TI  - Molecular self-assembly across multiple length scales.

PMID- 17497616
TI  - Isolation of high-affinity trypsin inhibitors from a DNA-encoded chemical
      library.

PMID- 17497617
TI  - Total synthesis and stereochemistry of uncialamycin.

PMID- 17497618
TI  - A concerted approach for the determination of molecular conformation in ordered
      and disordered materials.
AB  - We present the successful application of a concerted approach for the
      investigation of the local environment in ordered and disordered phases in the
      solid state. In this approach we combined isotope labeling with computational
      methods and different solid-state NMR techniques. We chose triphenylphosphite
      (TPP) as an interesting example of our investigations because TPP exhibits two
      crystalline modifications and two different amorphous phases one of which is
      highly correlated. In particular we analyzed the conformational distribution in
      three of these phases. A sample of triply labeled 1-[13C]TPP was prepared and 1D
      MAS as well as wide-line 13C NMR spectra were measured. Furthermore we acquired
      2D 13C wide-line exchange spectra and used this method to derive highly detailed
      information about the phenyl orientation in the investigated TPP phases. For
      linkage with a structure model a DFT analysis of the TPP molecule and its
      immediate environment was carried out. The ab initio calculations of the 13C
      chemical shift tensor in three- and six-spin systems served as a base for the
      calculation of 1D and 2D spectra. By comparing these simulations to the
      experiment an explicit picture of all phases could be drawn on a molecular level.
      Our results therefore reveal the high potential of the presented approach for
      detailed studies of the mesoscopic environment even in the challenging case of
      amorphous materials.

PMID- 17497619
TI  - Use of ionic liquids in the synthesis of nanocrystals and nanorods of
      semiconducting metal chalcogenides.
AB  - We have synthesized nanoparticles of hexagonal CdS in the diameter range 3-13 nm
      by the reaction of cadmium acetate dihydrate with thioacetamide in imidazolium
      [BMIM]-based ionic liquids. We have obtained three different particle sizes of
      CdS by changing the anion of the ionic liquid. Addition of trioctylphosphine
      oxide (TOPO) to the reaction mixture causes greater monodispersity as well as
      smaller particle size, while addition of ethylenediamine produces nanorods of 7
      nm average diameter. Hexagonal ZnS and cubic PbS nanoparticles with average
      diameters of 3 and 10 nm, respectively, have been prepared by the reaction of the
      metal acetates with thioacetamide in [BMIM][BF4]. Hexagonal CdSe nanoparticles
      with an average diameter 12 nm were obtained by the reaction of cadmium acetate
      dihydrate with dimethylselenourea in [BMIM][BF4]. In this case also we observe
      the same effect of the addition of TOPO as in the case of CdS. Addition of
      ethylenediamine to the reaction mixture gives rise to nanorods. ZnSe nanowires
      with a cubic structures, possible diameters in the range 70-100 nm by the
      reaction of zinc acetate dihydrate with dimethylselenourea in [BMIM][MeSO4]. The
      nanostructures obtained are single crystalline in all the cases. Most of the
      nanostructures show characteristic UV/Vis absorption and photoluminescence
      emission spectra. The thermodynamically most stable structures are generally
      produced in the synthesis carried out in ionic liquids.

PMID- 17497620
TI  - Structure of Ag clusters Grown on Fs-Defect Sites of an MgO(1 0 0) surface.
AB  - The structure of AgN clusters (N=1-4, 6, 8, 10), both in the gas phase and grown
      on the MgO(1 0 0) surface containing Fs-defects, has been investigated by a
      density functional basin-hopping (DF-BH) approach. In analogy with what observed
      in the case of gold clusters, it is found that the presence of the defect implies
      a double frustration and a cylindrical invariance of the metal-surface
      interaction, causing small Ag clusters growing around the Fs defect to be highly
      fluxional. Nevertheless, two different structural crossovers are found to be
      induced by the metal-defect interaction for the adsorbed clusters such that: 1)
      planar structures prevail for N<or=4 (as in the gas phase); 2) noncrystalline
      (fivefold symmetric) structures, which are the lowest energy ones in the gas
      phase for medium sized AgN clusters (N>or=7), prevail for N=6 and N=8; 3)
      distorted face-centered cubic (fcc) structures grown pseudomorphically on the
      defected surface prevail for N=10. The transition from fivefold to fcc motifs is
      rationalized in terms of the double-frustration effect, which increases the bond
      strain of the noncrystalline structures. Detrapping energies from the defect were
      also calculated; the lowest energy pathway corresponds to the detachment of a
      dimer.

PMID- 17497621
TI  - Gold nanoparticles in organic capsules: a supramolecular assembly of gold
      nanoparticles and cucurbituril.
AB  - Gold nanoparticles (<or=1 nm) have been encapsulated inside cucurbit[7]uril
      (CB[7]) by vapor deposition or chemical reduction in aqueous solutions. CB[7] has
      unique host properties compared with CB[5] and CB[6]. The particle size
      distribution obtained with CB[5] and CB[6] is similar to that obtained in the
      absence of CBs and the particles obtained are much too large to be incorporated
      inside the organic capsules. When gold nanoparticles are prepared inside CB[7]
      the resulting supramolecular assembly has shape-selective properties for gold
      interactions with amines, cyanide, and quaternary ammonium ions. Thus, CB[7] has
      the potential to be used in applications such as selective adsorption, sensing,
      and catalysis.

PMID- 17497622
TI  - Highly efficient synthesis of stereodefined multisubstituted 1,4-dicyano- and 1
      cyano-1,3-butadienes and their reactions with organolithium reagents.
AB  - Stereodefined multisubstituted 1-cyano- and 1,4-dicyano-1,3-butadiene derivatives
      were obtained in excellent yields of the isolated product from their
      corresponding monohalo- and dihalobutadienes and CuCN. This reaction proceeded
      with high stereoselectivity and retention of the stereochemistry of the starting
      halobutadienes. A study of the utility of the thus-obtained 1-cyano- and 1,4
      dicyano-1,3-butadiene derivatives was demonstrated by their reactions with
      organolithium reagents. 2H-Pyrrole or iminocyclopentadiene derivatives were
      formed in high yields from 1-cyano-4-halo-1,3-butadienes and organolithium
      reagents. When 1,4-dicyano-1,3-butadienes were treated with organolithium
      reagents followed by trapping with electrophiles, a tandem process took place to
      afford 2H-pyrrolyl nitriles in excellent yields. Reduction of 1,4-dicyano-1,3
      butadiene derivatives with LiAlH4 showed novel reaction patterns relative to
      normal nitriles.

PMID- 17497623
TI  - Synthesis and evaluation of modified oligodeoxynucleotides containing
      diphosphodiester internucleotide linkages.

PMID- 17497624
TI  - Metabolite identification by data-dependent accurate mass spectrometric analysis
      at resolving power of 60,000 in external calibration mode using an LTQ/Orbitrap.
AB  - Performance evaluation of accurate mass measurement by the LTQ/Orbitrap, at a
      resolving power of 60,000 and in external calibration mode, indicated that the
      Orbitrap is capable of providing high mass accuracy of <2 ppm for over 24 h post
      calibration. This, together with limited trade-off between sensitivity and
      resolving power plus a wide dynamic range for mass accuracy, suggested that the
      LTQ/Orbitrap is an ideal analytical tool for structural elucidation of
      metabolites. The application of the LTQ/Orbitrap to identification of human liver
      microsomal metabolites of carvedilol was evaluated, using parent mass list
      triggered data-dependent multiple-stage accurate mass analysis, at a resolving
      power of 60,000 in external calibration mode. A metabolite identification
      workflow was developed to utilize chemical formulas from high-resolution accurate
      mass measurements to confirm structures of product ions of a drug proposed by
      Mass Frontier, illustrated by identification of structures used to establish
      lineage of product ions of carvedilol, which later served as a template for
      identification of its metabolites. A total of 58 in vitro metabolites of
      carvedilol were detected using 5-ppm mass tolerance filters for theoretical m/z
      of protonated molecules of predicted metabolites in addition to product ions and
      neutral mass losses diagnostic of carvedilol. The chemical formulas with
      unsaturation numbers calculated from the accurate m/z of precursor and product
      ions can be used to assign, with a high degree of confidence, the structures of
      metabolites and the sites of metabolism. The mass accuracies obtained for all
      full scan MS and MSn spectra were <2 ppm. The majority of the metabolites
      identified agreed with those previously reported except for those that have not
      been reported before. For example, several glutathione conjugates of carvedilol
      were reported for the first time, which may explain the reported hepatotoxicity
      during clinical trials and recent clinical use.

PMID- 17497625
TI  - High-performance liquid chromatography-diode array detection/electrospray
      ionization mass spectrometry for the simultaneous analysis of cis-, trans- and
      dihydro-2-glucosyloxycinnamic acid derivatives from Dendrobium medicinal plants.
AB  - Sensitive, selective and reliable high-performance liquid chromatography (HPLC)
      diode array detection (DAD)/electrospray ionization multi-stage mass spectrometry
      (ESI-MSn) methods have been developed for the characterization of nine 2
      glucosyloxycinnamic acid derivatives and quantitative analysis of three of the
      major 2-glucosyloxycinnamic acids, cis-melilotoside, trans-melilotoside and
      dihydromelilotoside, present in Dendrobium medicinal plants. The identities of
      the latter three major 2-glucosyloxycinnamic acids were confirmed by comparing
      their retention times, UV and mass spectra with those of the reference standards.
      The characteristic ESI-MSn fragmentation patterns of the remaining six 2
      glucosyloxycinnamic acid derivatives, which are similar to the three major
      compounds, have allowed the putative elucidation of their structures. The
      concentrations of the cis-, trans- and dihydromelilotosides were simultaneously
      determined by HPLC/ESI-MS2 using the multiple reaction monitoring (MRM) mode in
      extracts of Dendrobium species. The method was validated with respect to the
      overall intra- and inter-day variation (RSD less than 8%) and the limits of
      quantification for the cis-, trans- and dihydromelilotosides were 0.09, 0.09 and
      0.01 microg/mL, respectively.

PMID- 17497626
TI  - Variability of the paracingulate sulcus and morphometry of the medial frontal
      cortex: associations with cortical thickness, surface area, volume, and sulcal
      depth.
AB  - The structural and functional consequences of interindividual variations in
      cortical morphology are poorly understood. In this study, we examined the
      relationship between one well-characterized variation of the medial frontal
      lobes, variability of the paracingulate sulcus (PCS), and grey matter volume,
      cortical thickness, surface area, and sulcal depth of the adjacent anterior
      cingulate cortex (ACC) and paracingulate cortex (PaC). Seventy-seven healthy
      individuals were assigned to one of four groups depending on PCS incidence in
      both hemispheres: left-present, right-absent; left-absent, right-present; both
      absent; or both present. Comparing these groups on each measure yielded four
      primary findings: (1) The presence of a PCS was associated with increased PaC and
      decreased ACC grey matter volume in the hemisphere in which it was apparent, with
      an almost identical pattern being observed for surface area; (2) there was a more
      complex relationship between PCS variability and regional thickness, such that a
      PCS in the left hemisphere was associated with increased left PaC and right ACC
      thickness, with no comparable effects being observed for the presence of a right
      PCS; (3) the depths of all major left hemisphere sulci in the region were
      strongly positively correlated, whereas no such associations were apparent in the
      right hemisphere; and (4) a leftward asymmetry in PaC thickness was specifically
      associated with better performance on a test of spatial working memory ability.
      These results provide evidence for a complex interhemispheric relationship
      between sulcal variability and cortical morphometry, and indicate that such
      relationships may be important for understanding individual differences in
      cognitive abilities.

PMID- 17497627
TI  - Functional connectivity mapping using the ferromagnetic Potts spin model.
AB  - An unsupervised stochastic clustering method based on the ferromagnetic Potts
      spin model is introduced as a powerful tool to determine functionally connected
      regions. The method provides an intuitively simple approach to clustering and
      makes no assumptions of the number of clusters in the data or their underlying
      distribution. The performance of the method and its dependence on the intrinsic
      parameters (size of the neighborhood, form of the interaction term, etc.) is
      investigated on the simulated data and real fMRI data acquired during a
      conventional periodic finger tapping task. The merits of incorporating Euclidean
      information into the connectivity analysis are discussed. The ability of the
      Potts model clustering to uncover the hidden structure in the complex data is
      demonstrated through its application to the resting-state data to determine
      functional connectivity networks of the anterior and posterior cingulate cortices
      for the group of nine healthy male subjects.

PMID- 17497628
TI  - Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist
      [11C]raclopride in healthy humans.
AB  - The D(2) receptors exist in either the high- or low-affinity state with respect
      to agonists, and while agonists bind preferentially to the high-affinity state,
      antagonists do not distinguish between the two states. [(11)C]-(+)-PHNO is a PET
      D(2) agonist radioligand and therefore provides a preferential measure of the
      D(2) (high) receptors. In contrast, [(11)C]raclopride is an antagonist
      radioligand and thus binds with equal affinity to the D(2) high- and low-affinity
      states. The aim was to compare the brain uptake, distribution and binding
      characteristics between [(11)C]-(+)-PHNO and [(11)C]raclopride in volunteers
      using a within-subject design. Both radioligands accumulated in brain areas rich
      in D(2)/D(3)-receptors. However, [(11)C]-(+)-PHNO showed preferential uptake in
      the ventral striatum and globus pallidus, while [(11)C]raclopride showed
      preferential uptake in the dorsal striatum. Mean binding potentials were higher
      in the putamen (4.3 vs. 2.8) and caudate (3.4 vs 2.1) for [(11)C]raclopride,
      equal in the ventral-striatum (3.4 vs. 3.3), and higher in the globus pallidus
      for [(11)C]-(+)-PHNO (1.8 vs. 3.3). Moreover [(11)C]-(+)-PHNO kinetics in the
      globus pallidus showed a slower washout than other regions. One explanation for
      the preferential binding of [(11)C]-(+)-PHNO in the globus pallidus and ventral
      striatum could be the presence of a greater proportion of high- vs. low-affinity
      receptors in these areas. Alternatively, the observed distribution could also be
      explained by a preferential binding of D(3)-over-D(2) with [(11)C]-(+)-PHNO. This
      differential binding of agonist vs. antagonist radioligand, especially in the
      critically important region of the limbic striatum/pallidum, offers new avenues
      to investigate the role of the dopamine system in health and disease.

PMID- 17497629
TI  - Levels of error processing in Huntington's disease: a combined study using event
      related potentials and voxel-based morphometry.
AB  - Huntington's Disease (HD) is a neurogenetic disorder accompanied by an atrophy of
      the striatum and hence of the dopaminergic (DA) system. Neural processes
      subserving error processing presumably depend on the DA system. We assessed error
      processing in manifest HD and in presymptomatic HD-gene-mutation-carriers (pHD)
      with event-related potentials reflecting error processing (the error negativity
      or error-related negativity and the error positivity derived from a flanker-task.
      We found a reduction of the Ne in the case of HD compared to pHD reflecting
      dopamine system pathology. Despite the Ne being reduced in HD, behavioral
      adaptation was possible. In addition, the error-rates did not differ between the
      groups. Optimized voxel-based morphometry revealed that grey matter volume in the
      medial frontal gyrus is correlated with the Ne amplitude in symptomatic patients.
      In addition, the effect of a Ne-reduction was related to the grey matter
      underneath the medial frontal gyrus, which is in line with two theories of the
      Ne. In contrast, the Pe did not differ between the groups, suggesting that the Pe
      is decoupled from the DA system. Interestingly we found a reduction of a late
      slow negativity on correct responses, which possibly reflects decreased
      preparatory processes in HD compared to pHD as induced by the DA alterations in
      HD. In conclusion a deterioration in error processing in HD compared to pHD is
      mainly reflected by the Ne. The deterioration might rely on two factors: a
      neurofunctional and a neuroanatomical.

PMID- 17497630
TI  - Brain potentials distinguish new and studied objects during working memory.
AB  - We investigated brain responses to matching versus nonmatching objects in working
      memory (WM) with a modified delayed match-to-sample task using event-related
      potentials (ERPs). In addition, ERP correlates of new items (new matches/new
      nonmatches) and previously studied items (studied matches/studied nonmatches)
      were examined in the WM task. Half of the common visual objects were initially
      studied until 95% accuracy was attained and half were new. Each memory trial
      began with the presentation of a sample object followed by nine test objects.
      Participants indicated whether each test item was the same as the object held in
      mind (i.e., match) or a nonmatch. Compared to studied matches, new matches evoked
      activity that was 50 ms earlier and largest at frontal sites. In contrast, P3
      activity associated with studied nonmatches was larger than for new nonmatches at
      mostly posterior sites, which parallels previously reported old-new ERP effects.
      The ERP source analysis further confirms that the cortical mechanisms underlying
      matching objects and rejecting irrelevant objects during the task are both
      temporally and spatially distinct. Moreover, our current findings suggest that
      prior learning affects brain responses to matching visual items during a WM task.

PMID- 17497631
TI  - Localization of human intraparietal areas AIP, CIP, and LIP using surface
      orientation and saccadic eye movement tasks.
AB  - In monkeys, areas in the intraparietal sulcus (IPS) play a crucial role in
      visuospatial information processing. Despite many human neuroimaging studies, the
      location of the human functional homologs of some IPS areas is still a matter of
      debate. The aim of the present functional magnetic resonance imaging (fMRI) study
      was to identify the distinct locations of specific human IPS areas based on their
      functional properties using stimuli adapted from nonhuman primate experiments, in
      particular, surface orientation discrimination and memory guided saccadic eye
      movements (SEM). Intersubject anatomical variability likely accounts for much of
      the debate. By applying subject by subject analysis, we can demonstrate that
      sufficient intersubject anatomical and functional commonalities exist. Both the
      lateral bank of the anterior part of IPS, the putative human homolog of the area
      AIP, and the caudal part of the IPS (putative CIP) showed activation related to
      spatial discrimination of surface orientation. Eye tracking conducted during fMRI
      data acquisition allowed us to show that both areas were separated by an area
      related to SEM. This area was located in the middle region of the IPS (most
      probably including LIP), i.e., similar to the location observed in nonhuman
      primates. In 10 of 11 subjects our putative CIP activation was located in a
      medial side branch of the posterior part of the IPS, on the opposite side as
      described in nonhuman primates, making this landmark a useful anatomical marker
      for the location of CIP.

PMID- 17497632
TI  - Copper and zinc tolerance of two tropical microalgae after copper acclimation.
AB  - Current toxicity tests with microalgae are often criticized as being overly
      sensitive to metals because algae are cultured in metal-deficient media. If such
      bioassays overestimate copper toxicity in surface waters, the relevance of water
      quality guidelines derived from these tests is questionable. In this study, the
      effect of acclimation to copper at environmentally relevant concentrations, on
      the sensitivity of the marine diatom Nitzschia closterium and the freshwater
      green alga Chlorella sp. to copper and zinc was examined. N. closterium was
      acclimated in culture medium containing 5 or 25 microg Cu L(-1) for 200 days,
      while Chlorella sp. was acclimated in medium containing 2 microg Cu L(-1) for 100
      days. Changes in algal growth rates and copper and zinc tolerance were monitored
      using standard growth inhibition toxicity tests in minimal medium over 72 h.
      Neither of the two acclimated N. closterium cultures had increased zinc or copper
      tolerance compared with that of the nonacclimated algae, nor were there any
      changes in control growth rates. Similarly, no changes in copper tolerance or
      control growth rates were observed for the acclimated Chlorella sp. culture. This
      was supported by measurements of intracellular and extracellular copper which
      confirmed that there were no differences in copper accumulation in either
      acclimated or nonacclimated algae. These results suggest that these algae grown
      in standard culture media are generally no more sensitive than algae grown in a
      metal-enriched medium. This supports the continued use of current laboratory
      bioassays with microalgae, as part of a suite of tests for assessing metal
      bioavailability, for use in ecological risk assessments and for providing data
      for the derivation of water quality guidelines.

PMID- 17497633
TI  - Antibiotic from the marine environment with antimicrobial fouling activity.
AB  - The degradation in performance of submerged marine structures through their
      colonization by micro- and macrobiota is well known. Historically, toxic surface
      coatings have been used to control both types of fouling. Legislative
      requirements worldwide now require alternative non- or minimally toxic coatings
      to be used. Here we report on the potential for synthetic 2-pentyl-4-quinolinol
      (PQ), an antibiotic from an Alteromonas sp., as a candidate antifoulant. Hundred
      micromolar PQ reduces the growth of four marine diatoms that usually grow as
      biofilms. Furthermore, PQ inhibits the initial adhesive process in Amphora
      coffeaeformis in a logarithmic dose-dependent manner, but not the adhesion of a
      Navicula sp., indicating differing adhesive processes in these two diatoms.
      Treatment of established biofilms with PQ causes a rapid and complete loss of
      motility in both Amphora and Navicula and eventually, as seen by Sytox Green
      staining, cell death, and lysis. We conclude that PQ, or one of its chemical
      analogues, holds promise as an antifoulant molecule for inclusion in marine
      surface coating.

PMID- 17497634
TI  - Removal of estrogenic activity of 4-tert-octylphenol by ligninolytic enzymes from
      white rot fungi.
AB  - 4-tert-Octylphenol (4-t-OP) was treated with the white rot fungus Phanerochaete
      sordida YK-624 under ligninolytic condition with low-nitrogen and high-carbon
      culture medium. 4-t-OP completely disappeared after 5 days of treatment and the
      activities of ligninolytic enzymes, laccase and manganese peroxidase (MnP), were
      detected during this period, thus suggesting that the disappearance of 4-t-OP is
      related to these extracellular enzymes. Therefore, 4-t-OP was treated with
      laccase and MnP prepared from white rot fungi cultures. HPLC analysis
      demonstrated that 4-t-OP completely disappeared in the reaction mixture after 1 h
      of treatment with either laccase or MnP. Using the yeast two-hybrid assay system,
      it was also confirmed that laccase and MnP substantially removed the estrogenic
      activity of 4-t-OP after 1 and 2 h of treatment, respectively. These results
      strongly demonstrate that ligninolytic enzymes are effective in removing the
      estrogenic activity of 4-t-OP.

PMID- 17497635
TI  - Lethal and sublethal responses of an aquatic insect Culex quinquefasciatus
      (Diptera: Culicidae) challenged with individual and joint exposure to dissolved
      sodium selenate and methylmercury chloride.
AB  - Pollutants rarely occur alone in the natural environment, and few studies have
      focused on the potential interactions between metals or metalloids. In this study
      an aquatic insect, the southern house mosquito (Culex quinquefasciatus: Diptera),
      was used to test the individual and joint effects of dissolved sodium selenate
      (Se) and methyl mercury chloride (MeHg). We conducted ovipositional preference
      tests and 14-day chronic toxicity studies to determine lethal and sublethal
      responses of C. quinquefasciatus to a range of Se and MeHg concentrations and
      mixtures. No evidence was found for female ovipositional preference in field
      trials using artificial ponds. Larvae were more sensitive to MeHg than Se, with
      LC(50) values of 30 microg/L (CI = 28-31 microg/L) and 11 mg/L (CI = 10-12 mg/L)
      respectively. In addition, larval survival was significantly reduced at
      concentrations as low as 25 microg/L of MeHg and 8 mg/L of Se. A synergistic
      interaction was observed in the toxicity of the Se-MeHg mixtures to C.
      quinquefasciatus larvae. Larval mosquito survival was significantly reduced at
      7.5 microg/L MeHg + 2.75 mg/L Se and an LC(50) value of 9 microg/L MeHg + 3.4
      mg/L Se was determined for a fixed ratio mixture. The rate of growth of the
      larvae was analyzed using a Growth Index that provided a sensitive measure of the
      developmental effects of toxicant exposure. Sodium selenate at concentrations as
      low as 2 mg/L caused a significant decrease in growth between larvae in treatment
      versus control solutions after only 4 days. Similarly, MeHg at concentrations as
      low as 25 microg/L and a Se-MeHg mixture of 3 microg/L MeHg plus 1.1 mg/L Se
      caused significant growth reductions after only 2 and 3 days, respectively. These
      are the first reported survival and developmental data for an aquatic insect
      exposed to MeHg and Se-MeHg mixtures.

PMID- 17497636
TI  - Predicting acute copper toxicity to valve closure behavior in the freshwater clam
      Corbicula fluminea supports the biotic ligand model.
AB  - The objective of this paper is to employ biotic ligand model (BLM) to link
      between acute copper (Cu) toxicity and its effect on valve closure behavior of
      freshwater clam Corbicula fluminea in order to further support for the BLM that
      potentially offers a rapid and cost-effective method to conduct the acute
      toxicity tests for freshwater clam exposed to waterborne Cu. Reanalysis of
      published experimental data of C. fluminea closure daily rhythm and dose-response
      profiles based on the laboratory-acclimated clams showed that a BLM-based Hill
      model best described the free Cu(2+)-activity-valve closure response
      relationships. Our proposed Cu-BLM-Corbicula model shows that free ionic form of
      waterborne Cu binds specifically to a biotic ligand (i.e., clam gills) and
      impairs normal valve closure behavior, indicating that a fixed-level of metal
      accumulation at a biotic ligand is required to elicit specific biological
      effects. With derived mechanistic-based Cu-BLM-Corbicula model, we show that the
      site-specific EC50(t) and valve closure behavior at any integrated time can be
      well predicted, indicating that our model has the potential to develop a
      biomonitoring system as a bioassay tool to on-line measure waterborne Cu levels
      in aquatic systems. Our results confirm that BLM can be improved to analytically
      and rigorously describe the bioavailable fraction of metal causing toxicity to
      valve closure behavior in freshwater C. fluminea. We suggest that the Cu-BLM
      Corbicula model can be used to assist in developing technically defensible site
      specific water quality criteria and performing ecological risk assessment and to
      promote more focused and efficient uses of resources in the regulation and
      control of metals and the protection of the aquatic ecosystems.

PMID- 17497637
TI  - Light-induced cytotoxicity of 16 polycyclic aromatic hydrocarbons on the US EPA
      priority pollutant list in human skin HaCaT keratinocytes: relationship between
      phototoxicity and excited state properties.
AB  - The photocytotoxicity of 16 polycyclic aromatic hydrocarbons (PAHs) on the
      priority pollutant list of the United States Environmental Protection Agency (US
      EPA) were tested in human skin HaCaT keratinocytes. A selected PAH was mixed with
      HaCaT cells and irradiated with a solar simulator lamp for a dose equivalent to 5
      min of outdoor sunlight and the cell viability was determined immediately and
      also after 24 h of incubation. For the cells without incubation after the
      treatments, it is found that all PAHs with three rings or less, except
      anthracene, are not photocytotoxic, while the four or five-ring PAHs (except
      chrysene), benz[a]anthracene, dibenzo[a,h]anthracene, benzo[ghi]perylene,
      benzo[a]pyrene, indeno[1,2,3-cd]pyrene, benzo[b]fluorenthene, fluorenthene, and
      pyrene, are photocytotoxic to the human skin HaCaT keratinocytes. If the cells
      were incubated for 24 h after the treatments, the photocytotoxic effect of the
      PAHs was greatly amplified in comparison to the nonincubated cells. For the 24 h
      incubated cells, all PAHs except naphthalene exhibit photocytotoxicity to some
      extent. Exposure to 5 microM of the 4- and 5-ring PAHs (except chrysene) and 3
      ring anthracene more than 80% of the cells lose viability. The photocytotoxicity
      of the PAHs correlates well with several of their excited state properties: light
      absorption, excited singlet-state energy, excited triplet-state energy, and HOMO
      LUMO energy gap. All the photocytotoxic PAHs absorb light at >300 nm, in the
      solar UVB and UVA region. There is a threshold for each of the three excited
      state descriptors of a photocytotoxic PAH: singlet energy <355 kJ/mol
      (corresponding to 337 nm light), triplet energy <230 kJ/mol (corresponding to 520
      nm light), HOMO-LUMO gap <3.6 eV (corresponding to 344 nm light) obtained at the
      Density Functional Theory B3LYP/6-31G(d) level.

PMID- 17497638
TI  - Ultrastructural effects of DDT, DDD, and DDE on neural cells of the chicken
      embryo model.
AB  - Human exposure to environmental compounds with estrogenic activity and the
      potential effects on human health is the subject of ongoing scientific debates.
      Their potential effects raise concern regarding neurological development after
      prenatal exposure. Central to this debate is the pesticide 1,1,1-trichloro-2,2
      bis(4-chlorophenyl)ethane (DDT). Although it has apparent low acute toxicity in
      mammals, DDT has a long residual persistence and laboratory research has
      indicated that it acts on the CNS by interfering with Na(+)/K(+) pump mechanism
      of the neuronal membranes, causing disruption in Ca(2+) homeostasis. Potentially
      this may lead to both apoptosis and necrosis. The present study investigates the
      effects of DDT and two of its metabolites DDD and DDE on the ultramorphology of
      neural cells, using a previously published chicken embryo model. Results indicate
      cellular swelling, budding, and increased membrane permeability for all three
      chemicals, accompanied by karyolysis in the DDE group (typical features of
      oncosis). These results support the finding of other researchers as well as the
      concerns of the WHO that DDT and its metabolites may cause neurotoxicity after
      prenatal exposure.

PMID- 17497639
TI  - First report of microcystin-LR in the cyanobacterium Gloeotrichia echinulata.
AB  - Gloeotrichia echinulata is a bloom-forming cyanobacterium that is common in
      eutrophic lakes, and less prevalent but increasing in oligotrophic lakes. We used
      an enzyme-linked immunosorbent assay analysis to test for the presence of the
      hepatotoxin microcystin-LR (MC-LR) in G. echinulata collected from an
      oligotrophic lake in central New Hampshire, USA. We found that G. echinulata
      contained MC-LR at mean concentrations of 97.07 +/- 7.78 (1 s.e.) ng MC-LR g(-1)
      dry wt colonies. This suggests that recent outbreaks of G. echinulata in
      oligotrophic lakes used as water sources throughout New England (USA) may pose a
      health concern. The toxicity of G. echinulata reported here suggests the need for
      future monitoring of microcystins in oligotrophic lakes.

PMID- 17497640
TI  - Benchmark dose approach for renal dysfunction in workers exposed to lead.
AB  - Benchmark dose (BMD) and the lower confidence limit on the benchmark dose (BMDL)
      of blood lead were estimated to explore the biologic exposure limits for renal
      dysfunction caused by lead. One hundred thirty-five workers from one storage
      battery plant were selected as lead exposure group while 143 mechanics as the
      control. The relationship between the blood lead concentration and the urinary
      excretion of total protein (TP), beta2-microglobulin (beta2-MG), and N-acetyl
      beta-D-glucosaminidase (NAG) was studied. The quantal linear logistic regression
      model (BMDS Version 1.3.1) was used to calculate BMD and BMDL of blood lead. The
      results showed that the levels of NAG, beta2-MG, and TP in lead-exposed workers
      were higher than those of control group and elevated along with rising length of
      employment. The levels of three indices for renal dysfunction increased with the
      elevated blood lead. The BMD and BMDL of blood lead for renal dysfunction were
      from 299.4 to 588.7 microg/L and from 253.4 to 402.3 microg/L, respectively. The
      BMDL of blood lead was ranged from high to low as TP, beta2-MG, and NAG. It is
      suggested that the urinary NAG activity could be a sensitive and early biomarker
      of renal tubular dysfunction induced by lead. When assessing renal function in
      workers occupationally exposed to lead, a blood lead level of 250 microg/L could
      serve as a warning signal.

PMID- 17497642
TI  - Bioaccumulation and ROS generation in liver of freshwater fish, goldfish
      Carassius auratus under HC Orange No 1 exposure.
AB  - HC Orange No. 1 (CAS No. 54381-08-7, 2-nitro-4'-hydroxydiphenylamine) is used as
      a color additive in hair dyes. In this study, laboratory experiment was carried
      out to determine HC Orange No. 1 bioaccumulation and oxidative stress in the
      liver of freshwater fish, goldfish Carassius auratus. Fish were exposed to
      different concentrations (0.05, 0.1, 0.2, 0.5, and 1.0 mg/L) of HC Orange No. 1
      for 10 days, with one group assigned as control. The accumulation of HC Orange
      No. 1 in liver increased with the exposure concentration (R(2) = 0.94). A
      secondary spin trapping technique was used followed by electron paramagnetic
      resonance (EPR) analysis to study the reactive oxygen species (ROS) production.
      On the basis of the hyperfine splitting constants and shape of the EPR spectrum,
      the ROS generated in fish liver after exposure was identified as hydroxyl radical
      (*OH). There is a good correlation between the exposure concentrations and *OH
      generation (R(2) = 0.92). The *OH signal intensity of the EPR spectrum showed a
      significant increase (P < 0.05) when the HC Orange No. 1 concentration was 1.0
      mg/L, compared with that of the control. A good positive relationship (R(2) =
      0.95) was found between the *OH formation and accumulation level of HC Orange No.
      1 in liver. The changes of the activities of catalase (CAT), superoxide dismutase
      (SOD), glutathione S-transferase (GST), and contents of reduced glutathione (GSH)
      were also detected. These observations indicated a possible mechanism of
      oxidative stress induced by HC Orange No. 1 on fish.

PMID- 17497641
TI  - Effect of di(n-butyl) phthalate on testicular oxidative damage and antioxidant
      enzymes in hyperthyroid rats.
AB  - This study compared the effects of di(n-butyl) phthalate (DBP) on the oxidative
      damage and antioxidant enzymes activity in testes of hyperthyroid rats.
      Hyperthyroidism was induced in pubertal male rats by intraperitoneal injection of
      triiodothyronine (T3, 10 microg/kg body weight) for 30 days. An oral dose of DBP
      (750 mg/kg) was administered simultaneously to normal or hyperthyroid (T3) rats
      over a 30-day period. No changes in body weight were observed in the hyperthyroid
      groups (T3, T3 + DBP) compared with controls. There were significantly higher
      serum T3 levels observed in the hyperthyroid rats than in the control, but the
      serum thyroid stimulating hormone levels were markedly lower in the hyperthyroid
      rats. DBP significantly decreased the weight of the testes in the normal (DBP)
      and hyperthyroid (T3 + DBP) groups. The serum testosterone concentrations were
      significantly lower in only DBP group. DBP significantly increased the 8-hydroxy
      2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced 8-OHdG
      levels were slightly higher in T3 + DBP group. Superoxide dismutase and
      glutathione peroxidase activities were significantly higher in the testes of the
      DBP or T3 + DBP groups. Catalase (CAT) activity was significantly higher in the
      DBP treatment group, but the T3 + DBP group showed slightly lower DBP-induced CAT
      activity. The testicular expression of thyroid hormone receptor alpha-1 (TRalpha
      1) was significantly higher in the DBP groups, and androgen receptor (AR)
      expression was not detected in the DBP treatment group. In addition, DBP
      significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r)
      levels in the testis. These results suggest that hyperthyroidism can cause a
      change in the expression level of PPAR-r in testes, and may increase the levels
      of oxidative damage induced by the metabolic activation of DBP.

PMID- 17497644
TI  - Responses of Daphnia magna to pulsed exposures of arsenic.
AB  - Research on the toxicity of arsenic has focused on sublethal effects that do not
      provide sufficient information for risk estimation. While most studies have
      focused on organism response to constant arsenic exposures, organisms in nature
      are exposed to fluctuating As concentrations. Consequently, results obtained from
      standardized bioassays with constant exposures may not adequately characterize
      risk to indigenous biota. This research was designed to characterize the response
      of Daphnia magna to fluctuating arsenic exposures during 21-day experiments. At
      concentrations > or =3000 microg/L As, 21-day pulsed exposure mortality increased
      as a function of exposure concentration and duration. In addition, 21-day pulsed
      exposure mortality increased with increasing recovery time. Pulsed As exposure
      did not affect the growth of D. magna over 21 days. Twenty-one day accumulative
      reproduction of D. magna was only affected by pulsed exposures of high As
      concentration and long durations.

PMID- 17497643
TI  - Subacute toxicity evaluation in rats exposed to concrete and hwangto building
      environments.
AB  - This study examined the potential adverse effects of the subacute exposure of
      rats to concrete and hwangto building environments. Polycarbonate was used as a
      comparison. Groups of 10 male rats were exposed to polycarbonate, concrete, or
      hwangto cages for a 4-week period in summer or winter. During the study period,
      the clinical signs, mortality, skin temperature, body weight, food consumption,
      ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ
      weights, and histopathology were examined. The concentration of total volatile
      organic compounds (VOCs), temperature, and relative humidity in the each cages
      were also measured. There were no exposure-related effects in any group of the
      study examined in the summer. The temperature, relative humidity, and the
      concentration of VOCs in the cages were similar in all groups. However, in the
      winter study, significant differences in several parameters were detected among
      the groups. In the concrete group, there was an increase in the clinical signs, a
      reduction in the body weight gain, food intake, and liver weight, an increase in
      the lung weight, and an increase in the histopathological alterations in the lung
      and thymus. Infrared thermal analysis showed that the skin temperature of the
      rats in the concrete group was lower than that in the polycarbonate group.
      However, in the hwangto group, there was a decrease in the clinical signs and an
      increase in the body weight, food intake, and the weights of the heart, lung,
      spleen, and epididymides. Overall, the 4-week exposure of the rats to the
      concrete building environment had adverse effects on the clinical signs, skin
      temperature, body weight, and some organs in the winter but not in the summer. On
      the other hand, the exposure of hwangto building environment did not have any
      exposure-related adverse effects on the general health parameters and skin
      temperature in rats.

PMID- 17497645
TI  - Prenatal three-dimensional ultrasound: perception of sonographers, sonologists
      and undergraduate students.
AB  - OBJECTIVE: To assess the perception of non-pregnant sonographers, sonologists and
      undergraduate students on the use of three-dimensional (3D) ultrasound technology
      in fetal medicine. METHODS: This was a study of two groups of non-pregnant
      subjects. Group I included 520 (305 female, 215 male) medical professionals who
      completed a questionnaire after attending a lecture on 3D imaging. Factors such
      as gender, career and having children were analyzed with respect to the
      attendee's responses about use of 3D ultrasound for medical purposes and for
      reassurance. Group II included 137 (75 female, 60 male, two unknown)
      undergraduate students from bioengineering, psychology and physiology classes who
      completed a questionnaire after attending a brief presentation on two-dimensional
      and 3D fetal imaging. Factors such as gender and area of educational interest
      were analyzed with respect to the students' responses about the use of 3D
      ultrasound for medical purposes and for parental-fetal attachment. RESULTS: In
      Group I, 63% said that they would like to have a 3D ultrasound examination in the
      future, while 14% said that they would not. Common reasons given for wanting a 3D
      ultrasound exam in the future were for medical purposes (39%) or reassurance
      (18%). The main differences perceived between two-dimensional (2D) and 3D
      ultrasound were medical advantages (65%) and parental reassurance (28%). 62.4% of
      Group I thought 3D technology should be in wide use in obstetric ultrasound and
      73.6% thought that 3D ultrasound would reassure parents carrying normal fetuses.
      Gender, age and career did not have a significant influence on perception of 3D
      ultrasound. In Group II, the majority (91%) said they could see a remarkable
      difference between 2D and 3D ultrasound. 83% responded that they would like to
      have a 3D ultrasound examination of their own baby in the future for the
      following reasons: 34% for the detailed picture, 31% for increased abnormality
      detection, 13% for reassurance or curiosity; 8% thought it would be unnecessary
      or a negative experience. Concerning parental-fetal attachment, 72% thought 3D
      ultrasound would have a positive effect. The majority of Group II (93%) thought
      3D ultrasound would be valuable and 56% thought 3D ultrasound would assist in
      diagnosing fetal abnormalities. There was no significant relationship between
      gender, age or area of interest and the perception of 3D ultrasound. CONCLUSIONS:
      Responses by sonographers and physicians suggest that 3D ultrasound will have a
      role in the future for medical indications and in reassuring patients carrying
      normal fetuses. Our results also suggest that undergraduate students believe that
      3D ultrasound will be a valuable technique in obstetrics and that it will have a
      positive effect on parental-fetal attachment.

PMID- 17497646
TI  - Cross-cultural music phrase processing: an fMRI study.
AB  - The current study used functional magnetic resonance imaging (fMRI) to
      investigate the neural basis of musical phrase boundary processing during the
      perception of music from native and non-native cultures. German musicians
      performed a cultural categorization task while listening to phrased Western
      (native) and Chinese (non-native) musical excerpts as well as modified versions
      of these, where the impression of phrasing has been reduced by removing the
      phrase boundary marking pause (henceforth called "unphrased"). Bilateral planum
      temporale was found to be associated with an increased difficulty of identifying
      phrase boundaries in unphrased Western melodies. A network involving frontal and
      parietal regions showed increased activation for the phrased condition with the
      orbital part of left inferior frontal gyrus presumably reflecting working memory
      aspects of the temporal integration between phrases, and the middle frontal gyrus
      and intraparietal sulcus probably reflecting attention processes. Areas more
      active in the culturally familiar, native (Western) condition included, in
      addition to the left planum temporale and right ventro-medial prefrontal cortex,
      mainly the bilateral motor regions. These latter results are interpreted in light
      of sensorimotor integration. Regions with increased signal for the unfamiliar,
      non-native music style (Chinese) included a right lateralized network of angular
      gyrus and the middle frontal gyrus, possibly reflecting higher demands on
      attention systems, and the right posterior insula suggesting higher loads on
      basic auditory processing.

PMID- 17497647
TI  - Endogenous secretory receptor for advanced glycation endproducts as a novel
      prognostic marker in chondrosarcoma.
AB  - BACKGROUND: Chondrosarcoma, the second most frequent primary malignant bone
      tumor, is classified into 3 grades according to histologic criteria of
      malignancy. However, a low-grade lesion can be difficult to distinguish from a
      benign enchondroma, whereas some histologically low-grade lesions may carry a
      poor prognosis. The receptor for advanced glycation endproducts (RAGE) and its
      ligand, high-mobility group box-1 (HMGB1), was quantified in enchondromas and
      chondrosarcomas to determine whether these markers were associated with
      histological malignancy and prognosis. METHODS: Enchondromas (n = 20) and typical
      chondrosarcomas (n = 39) were evaluated for RAGE, endogenous secretory RAGE
      (esRAGE, a splice variant form), and HMGB1 protein expression by
      immunohistochemistry including laser confocal microscopy. The content of esRAGE
      in resected specimens was measured with an enzyme-linked immunosorbent assay.
      Associations of these molecules with histology and clinical behavior of tumors
      were analyzed. RESULTS: Expression of esRAGE and HMGB1 was observed in all
      specimens. The numbers of cells positive for esRAGE and HMGB1 expression were
      positively associated with histologic grade. Expression of esRAGE was
      significantly higher in chondrosarcomas than in enchondromas (P < .001). Tissue
      esRAGE content was also significantly higher in grade 1 and 2 chondrosarcomas
      than enchondromas (P = .0255 and P = .008, respectively). High expression of
      esRAGE in grade 1 chondrosarcoma was associated with subsequent recurrence (P =
      .0013), lung metastasis (P = .0071), and poor survival (P < .001). CONCLUSIONS:
      Assessment of esRAGE expression should aid in diagnostic and prognostic
      determinations in chondrosarcoma.

PMID- 17497648
TI  - Pretransplant positive positron emission tomography/gallium scans predict poor
      outcome in patients with recurrent/refractory Hodgkin lymphoma.
AB  - BACKGROUND: The objective was to determine the prognostic value of functional
      imaging (FI) in predicting outcome of patients with recurrent/refractory Hodgkin
      lymphoma (HL) before undergoing high-dose chemotherapy with autologous stem cell
      transplantation (ASCT). METHODS: Clinical and imaging data were retrospectively
      reviewed in 211 consecutive patients treated with ASCT from February 1993 to May
      2004. The FI results were correlated with progression-free survival (PFS) and
      overall survival (OS) using Kaplan-Meier survival analysis. RESULTS: Responses
      were assessed by conventional criteria and evaluated by positron emission
      tomography (PET) (n = 68) and gallium scans (n = 144) before ASCT. A complete
      response (CR) or unconfirmed CR (CRu) was seen in 51% of patients, a partial
      response (PR) in 41% of patients, and stable or progressive disease in 7% of
      patients. FI was positive in only 6 of 110 (5%) of CR/CRu patients, in 48 of 86
      (56%) of PR patients, and in all 3 patients with progressive disease. The 3-year
      PFS was 69% for patients with negative FI versus 23% for patients with positive
      FI (P < .0001). The 3-year OS rates were 87% and 58%, respectively (P < .0001).
      The 3-year PFS for patients in PR with negative FI was 51% comparable to patients
      in CR (76%) versus 27% for patients in PR with positive FI (P < .0001). In a
      multivariate model, positive FI was found to be independently prognostic of PFS.
      CONCLUSIONS: Pretransplant FI status predicts outcome in patients with
      recurrent/refractory HL. Positive FI confers a poor prognosis, independent of
      other traditional presalvage prognostic factors.

PMID- 17497649
TI  - Clinical predictors of Gleason score upgrading: implications for patients
      considering watchful waiting, active surveillance, or brachytherapy.
AB  - BACKGROUND: Brachytherapy, active surveillance, and watchful waiting are
      increasingly being offered to men with low-risk prostate cancer. However, many of
      these men harbor undetected high-grade disease (Gleason pattern > or =4). The
      ability to identify those individuals with occult high-grade disease may help
      guide treatment decisions in this patient cohort. METHODS: The authors identified
      175 cases of low-risk prostate cancer treated with radical prostatectomy. By
      using logistic regression analysis, 11 a priori-defined preoperative risk factors
      were evaluated for their ability to predict upgrading from Gleason 6 at biopsy to
      Gleason > or =7 at radical prostatectomy. An internally validated nomogram using
      all clinical variables was subsequently created to help physicians identify
      patients who had undetected high-grade disease. RESULTS: A total of 60 (34%)
      patients were upgraded to high-grade disease. On multivariate analyses, both
      prostate-specific antigen (PSA) level (P = .02) and the level of pathologist
      expertise (P = .007) were predictive of upgrading. The predictive nomogram
      contained these variables plus age, digital rectal examination, transrectal
      ultrasound results, biopsy scheme applied (sextant vs extended), presence of
      prostatic intraepithelial neoplasia, prostate gland volume, and percentage of
      cancer in the biopsy. The nomogram provided acceptable discrimination (C
      statistic 0.71). CONCLUSIONS: The authors identified significant predictors of
      upgrading for patients diagnosed with low-risk prostate cancer. A nomogram based
      on these study findings could help physicians further risk-stratify patients with
      low-risk prostate cancer before embarking on treatment. Caution should be
      exercised in recommending nonradical therapy to individuals with a high
      probability of undetected high-grade disease.

PMID- 17497650
TI  - Identification of novel alternatively spliced BRCA1-associated RING domain
      (BARD1) messenger RNAs in human peripheral blood lymphocytes and in sporadic
      breast cancer tissues.
AB  - BARD1 (BRCA1-associated RING domain) is the dominant binding partner of BRCA1 in
      vivo. The BARD1 gene has been reported to be mutated in a subset of breast and
      ovarian cancer patients and BARD1 germ-line mutations have been identified in
      breast cancer patients negative for BRCA1 or BRCA2 gene alterations. In the
      present study, we show by RT-PCR and direct sequencing analysis the occurrence of
      seven novel and one previously identified BARD1 splicing variants in human
      lymphocytes and breast cancers. Two of the eight variants (BARD1delta and BARD1
      DeltaRIN) preserve a correct open reading frame and could encode BARD1 internally
      deleted proteins, while the remaining six variants display premature stop codons.
      Characterization of the relative expression of BARD1 FL, BARD1delta, and BARD1
      DeltaRIN using quantitative PCR analysis indicated that the mean expression
      levels of BARD1 FL, BARD1delta, and BARD1 DeltaRIN were significantly higher in
      tumors than in morphologically normal tissues and lymphocytes. However, we were
      unable to identify either qualitatively or quantitatively tumor-specific
      expression patterns of the identified BARD1 splicing variants.

PMID- 17497651
TI  - Factors affecting outcome following endoscopic thoracic sympathectomy.
AB  - BACKGROUND: Endoscopic thoracic sympathectomy (ETS) is an effective treatment for
      palmar hyperhidrosis and has been extended to craniofacial symptoms such as
      blushing and facial sweating. Adverse effects, including compensatory sweating,
      may cause patients to regret surgery. Such adverse events are currently
      unpredictable. This study investigated whether age, sex or bodyweight influenced
      the outcome. METHODS: A total of 110 patients who had bilateral ETS for palmar
      hyperhidrosis or facial symptoms (blushing or sweating) were asked to complete a
      questionnaire before and after surgery regarding physical and emotional symptoms,
      and overall satisfaction. RESULTS: Seventy-nine usable questionnaires were
      obtained. A decrease (an improvement) in physical symptom score was found in all
      patients; the median (interquartile range) change was - 15 (-9 to - 18) for
      facial symptoms and - 8 (-6.75 to - 9) for palmar symptoms. Similarly, there was
      an improvement in emotional symptom score of - 16 (-8 to - 28) for facial
      symptoms and - 13 (-7.25 to - 18.5) for palmar symptoms. More compensatory
      sweating was noted in those treated for facial symptoms (P = 0.007). There was no
      influence of age, sex or body mass index on outcome. CONCLUSION: ETS is an
      effective treatment for palmar and facial symptoms. Side-effects may be worse in
      patients treated for facial symptoms.

PMID- 17497652
TI  - Surgical treatment and outcome of iatrogenic bile duct lesions after
      cholecystectomy and the impact of different clinical classification systems.
AB  - BACKGROUND: Different injury patterns of iatrogenic bile duct lesions after
      cholecystectomy have prompted the proposal of several different clinical
      classification systems. The aim of this study was to validate these systems
      comparatively. METHODS: Results after surgical intervention for iatrogenic bile
      duct lesions in 74 consecutive patients at a tertiary referral centre were
      reviewed retrospectively. A new classification (Hannover classification) for
      iatrogenic bile duct lesions is proposed and compared with four other systems
      using the present clinical data. RESULTS: Additional vascular lesions were found
      in 19 per cent. The hospital mortality rate was 3 per cent and the overall
      hospital complication rate after repair was 26 per cent. Sixteen of 74 patients
      required early surgical reintervention. The Hannover classification demonstrated
      a highly significant association between the discrimination of classifiable
      injury patterns and the different surgical treatments chosen (P < 0.005). The
      Strasberg and Neuhaus classifications do not consider vascular involvement,
      whereas the Stewart-Way, Siewert and Neuhaus systems do not discriminate between
      lesions at or above the bifurcation of the hepatic duct. CONCLUSION: Additional
      vascular involvement and location of the lesion at or above the bifurcation of
      the hepatic duct have a major impact on the extent of surgical intervention
      required and should be reflected in any classification of bile duct injuries.

PMID- 17497653
TI  - Mild steatosis impairs functional recovery after liver resection in an
      experimental model.
AB  - BACKGROUND: Mild steatosis has been thought not to affect outcome after liver
      resection. However, recent studies have reported impaired postoperative recovery
      of patients with mild steatosis. This study evaluated the recovery of hepatic
      functional reserve during regeneration in a rat model of mild steatosis and liver
      resection. METHODS: Male Wistar rats had a standard methione- and choline
      deficient diet to induce mild steatosis before 70 per cent liver resection.
      Evaluation of hepatobiliary function was by (99m)Tc-labelled mebrofenin
      scintigraphy. Mebrofenin uptake rate, the time for maximum uptake (T peak) and
      the time required for peak activity to decrease by 50 per cent (T(1/2) peak) were
      assessed 1, 2, 3 and 7 days after liver resection, along with regeneration of the
      remnant liver, hepatocellular and sinusoidal damage, and hepatic adenosine 5'
      triphosphate (ATP) levels. RESULTS: Liver regeneration and proliferative response
      in mild steatotic rats were no different from those in controls. However, the
      mebrofenin uptake rate was lower (P < 0.050) and the recovery of hepatic ATP
      impaired (P < 0.050) in animals with mild steatosis. Hepatocellular damage was
      increased (P < 0.050) but sinusoidal endothelial cell function was not affected
      after liver resection in mildly steatotic rats. CONCLUSION: Mild steatosis
      impaired functional recovery and increased hepatocellular damage after liver
      resection.

PMID- 17497654
TI  - Management of mixed arterial and venous leg ulcers.
AB  - BACKGROUND: The aim was to assess healing in patients with mixed arterial and
      venous leg ulcers after protocol-driven treatment in a specialist leg ulcer
      clinic. METHODS: The study included consecutive patients referred with leg
      ulceration and venous reflux over 6 years. Legs without arterial disease (ankle :
      brachial pressure index (ABPI) above 0.85) were treated with multilayer
      compression bandaging and patients with severe disease (ABPI 0.5 or less) were
      considered for immediate revascularization. Those with moderate arterial
      compromise (ABPI above 0.5 up to 0.85) were initially managed with supervised
      modified compression and considered for revascularization if their ulcer did not
      heal. Healing rates were determined using life-table analysis. RESULTS: Of 2011
      ulcerated legs, 1416 (70.4 per cent) had venous reflux. Of these 1416, 193 (13.6
      per cent) had moderate and 31 (2.2 per cent) had severe arterial disease. Healing
      rates by 36 weeks were 87, 68 and 53 per cent for legs with insignificant,
      moderate and severe arterial disease respectively (P < 0.001). Seventeen legs
      with moderate and 15 with severe arterial disease were revascularized. Of these,
      ulcers healed in four legs with moderate and seven with severe disease within 36
      weeks of revascularization (P = 0.270). Combined 30-day mortality for
      revascularization was 6.5 per cent. CONCLUSION: A protocol including supervised
      modified compression and selective revascularization achieved good healing rates
      for mixed arterial and venous leg ulceration.

PMID- 17497655
TI  - Automated screening versus manual screening: a comparison of the ThinPrep imaging
      system and manual screening in a time study.
AB  - The ThinPrep Imaging System (TIS) is an automated system that assists
      cytotechnologists in the primary screening of ThinPrep liquid based cervical
      samples. Between June 1, 2004, and April 1, 2005, four experienced
      cytotechnologists participated in the study in which the duration of the
      screening procedure was timed for each of the 11,354 slides included. In every
      slide 22 fields of view were reviewed, and the samples that contained potentially
      abnormal cells were fully screened. The screening time was reduced by 42% (mean)
      (p < 0.001). By manual rescreening of the negative TIS samples, abnormal cells
      were found in 10 samples (false negative rate 0.14%). In every case the abnormal
      cells had been identified by the scanner, but misinterpreted by the
      cytotechnologist. These findings stressed the importance of carefulness in the
      interpretation of the marked fields and beyond that helped the cytotechnologists
      and pathologists to have more confidence in the automated system.

PMID- 17497656
TI  - The effects of antibody clone and pretreatment method on the results of HER2
      immunostaining in cytologic samples of metastatic breast cancer: A query and a
      review of the literature.
AB  - The standardization and use of heat-induced epitope retrieval (HIER) is
      particularly important with immunohistochemical markers that direct the course of
      cancer treatment, such as Herceptin therapy. Increasingly, many laboratories are
      performing immunohistochemical analysis using various antibodies and
      methodologies for HER2/neu. We attempted to determine the effects of antibody
      clone and pretreatment methods on the interpretation of HER-2/neu staining in
      cytologic samples. Cell block sections from 54 cases of metastatic breast cancer
      (24 FNAs, 30 effusions) were analyzed for HER2 expression using antibodies to CB
      11, TAB250, and A0485. Antibodies were analyzed with and without HIER. One
      pathologist using the FDA-approved scoring system for the HercepTest reviewed all
      slides in a blinded fashion. Five of fifty-four cases (9%) using CB-11 showed a
      significant increase in HER2 immunoreactivity using HIER (i.e. from 0/1+ to 2
      3+). However, in twenty-nine of fifty-four cases (54%), the cytoplasmic
      background was significantly higher after HIER. With the A0485 antibody, two of
      fifty four cases (4%) showed a significant increase in immunoreactivity using
      HIER, while seventeen of fifty-four cases (31%) exhibited only more pronounced
      cytoplasmic staining. HIER pretreatment did not increase HER2 staining in any
      TAB250 stained sample, rather four of fifty-four cases (7%) showed a significant
      decrease in staining with HIER. We conclude that HIER may enhance membrane
      staining with the CB-11 and A0485 antibodies, but also increases cytoplasmic
      background. Loss of antigenicity is seen when HIER is used with TAB250.

PMID- 17497657
TI  - Utility of microwave processed cell blocks as a complement to cervico-vaginal
      smears.
AB  - Cell blocks have largely been neglected in cervical cytology. The aim of this
      study was to determine if microwave processed cell blocks prepared from residual
      material on sampling devices could add to the diagnostic accuracy of cervico
      vaginal smears. The material remaining on the spatula after making cervical
      smears was rinsed in ethanol and used to prepare microwave-processed cell blocks
      in 260 patients. Both Papanicolaou (Pap) smears and cell block sections were
      examined independently. The sensitivity and specificity of both techniques for
      detection of malignancy and intraepithelial lesions were calculated. Sensitivity
      and specificity for cytology smear for detection of malignancy were 79.16% and
      100%, respectively. The sensitivity and specificity of cell block were 86.3% and
      100%, respectively. The quality of the section and staining after microwave
      processing was excellent. Our modified technique using microwave fixation and
      processing substantially reduced the turn around time. Microwave processed cell
      blocks prepared from residual cervico-vaginal specimens on sampling devices can
      add to the diagnostic accuracy of Pap smear without patients needing to undergo
      an additional procedure.

PMID- 17497658
TI  - Pulmonary metastasis of giant cell tumor of the bone diagnosed by fine-needle
      aspiration biopsy.
AB  - Giant cell tumor is a benign but locally aggressive tumor that primarily affects
      the epiphyses of long bones of young adults. Pulmonary metastases in giant cell
      tumor are rare (about 1-9%). Here, we report a case of metastatic pulmonary giant
      cell tumor in a patient who had a previous history of giant cell tumor of the
      distal femur with multiple recurrences. The diagnosis of pulmonary metastasis was
      achieved by cytologic evaluation with concurrent immunohistochemical studies in
      material obtained by fine-needle aspiration biopsy. The aspirate smears contained
      clustered and dispersed mononuclear and osteoclast-like giant cells that had
      bland nuclei with inconspicuous nucleoli. All multinucleated cells showed
      immunoreactivity to KP-1 antibody, a histiocytic marker (not lineage specific)
      and only a subset of mononuclear cells (30%) stained with this marker. Twenty
      percent of the mononuclear cells also displayed increased Ki-67 and p53 protein
      expression. The pulmonary metastasis was similar morphologically and
      immunophenotypically to the recurrent giant cell tumor of the bone.

PMID- 17497659
TI  - Giardia lamblia infection diagnosed by endoscopic ultrasound-guided fine-needle
      aspiration.
AB  - The protozoan Giardia lamblia is a major cause of gastrointestinal disease
      worldwide. We report the case of a 59-yr-old male who presented to his primary
      care physician with complaints of abdominal pain and weight loss. Imaging studies
      revealed a liver mass and a pancreatic head mass. Biopsy of the liver mass proved
      to be benign, and endoscopic ultrasound-guided fine-needle aspiration of the mass
      in the head of the pancreas showed no evidence of malignancy; however, numerous
      pear-shaped, binucleated, flagellated organisms morphologically consistent with
      trophozoites of Giardia lamblia were identified in the specimen. With the
      increasing use of endoscopic ultrasound-guided fine-needle aspiration for
      sampling of gastrointestinal, hepatobiliary, and pancreatic lesions,
      cytopathologists examining such specimens will need to be familiar with the
      diagnostic characteristics of this protozoal parasite.

PMID- 17497660
TI  - Cytological diagnosis of collagenous spherulosis of breast associated with
      fibroadenoma: report of a case with review of literature.
AB  - Collagenous spherulosis of the breast is a rare incidental finding frequently
      associated with other benign lesions of the breast. The estimated incidence of
      this innocuous condition is only about 0.2% in cytological material. It is of
      utmost importance to differentiate collagenous spherulosis from its malignant
      mimics to avoid unnecessary treatment. This article discusses the cytological
      findings of a case of collagenous spherulosis of breast associated with
      fibroadenoma, along with a brief review of literature.

PMID- 17497661
TI  - WT1, monoclonal CEA, TTF1, and CA125 antibodies in the differential diagnosis of
      lung, breast, and ovarian adenocarcinomas in serous effusions.
AB  - The distinction between metastatic adenocarcinomas of lung (LAC), breast (BAC),
      and ovary (OAC) in serous effusions can be very difficult since they all can
      present as tight cell clusters. This is particularly challenging when the
      malignant effusion is the patient's initial presentation or when the patient has
      a history of more than one primary. The aim of this study is to evaluate the
      usefulness of WT1, monoclonal CEA (mCEA), TTF1, and CA125 antibodies in the
      differential diagnosis of metastatic adenocarcinoma from the lung, breast and
      ovary in serous effusions. Forty-six samples of serous effusions with their
      corresponding cell blocks were retrieved from our hospital computer system,
      including 13 BACs, 13 LACs, and 20 OACs. The diagnoses were confirmed by the
      surgical resection. Formalin-fixed and paraffin-embedded cell block sections were
      immunostained for WT1, mCEA, TTF1, and CA125. Two observers blindly reviewed the
      immunostained slides without knowledge of the previous clinical or histologic
      diagnoses. The staining intensity was graded semiquantitatively as negative, 0;
      weak, 1+; moderate, 2+; and strong, 3+. The percentage of positively staining
      cells was estimated. The distribution patterns of reactivity for WT1 and TTF1
      were recorded as nuclear, and mCEA and CA125 as membranous stain. Metastatic OACs
      showed positive immunoreactivity to WT1 in 19/20 (95%) cases, CA125 in 20/20
      (100%), and all showed negative reaction for both mCEA (0/20, 0%) and TTF1 (0/20,
      0%). BAC showed positive reaction in 6/13 (46%) cases to CA125 and mCEA. Staining
      pattern was diffuse for CA125 and focal for mCEA. Only 2/13 (15%) were positive
      for WT1, while all of 13 BAC cases (0/13, 0%) were negative for TTF1. LAC showed
      positive immunoreactivity for TTF1 in 9/13 (69%) with a characteristic nuclear
      staining pattern, but only 3/13 (23%) were focally stained for WT1. In addition,
      8/13 (62%) of LAC cases were positive for both CA125 and mCEA. Our results
      demonstrate that the WT1 stain is specific for metastatic carcinoma of ovarian
      primary, showing a high sensitivity. In addition, CA125 stain is very sensitive
      for OACs, but could be positive in about a half of LAC and BAC cases. An
      immunostaining pattern of positive mCEA as well as negative WT1 rules out OACs,
      raising the possibility of LACs and BACs. A positive TTF1 staining supports the
      diagnosis of metastatic carcinoma originating from lung rather than breast, while
      a negative TTF1 favors the diagnosis of a breast primary. Immunohistochemical
      studies with WT1, TTF1, and mCEA antibodies are useful in the differential
      diagnosis of metastatic adenocarcinomas of lung, breast, and ovary.

PMID- 17497662
TI  - Fine-needle aspiration cytology of medullary breast carcinoma: report of two
      cases and review of the literature with emphasis on differential diagnosis.
AB  - Medullary carcinoma is a rare variant of breast carcinoma with a relatively good
      clinical prognosis as strictly defined. Characteristic features on fine-needle
      aspiration cytology (FNAC) allow medullary carcinoma to be considered in the
      cytologic differential diagnosis. We present two FNAC cases with such features,
      including high cellularity with clusters and single intact malignant cells,
      bizarre stripped nuclei with prominent nucleoli in a lymphoplasmacytic
      background, and illustrate one case in liquid-based preparation. Surgical
      excision revealed that one patient had medullary carcinoma, while the second
      patient had high-grade infiltrating ductal carcinoma. Breast FNAC samples with
      syncytial fragments, bizarre nuclei with prominent nucleoli, and a chronic
      inflammatory infiltrate should raise the possibility of medullary carcinoma.
      However, the differential diagnosis also includes high-grade ductal carcinoma,
      lymphoma, or metastasis to breast or intramammary lymph nodes; thus,
      histopathologic analysis is required for definitive diagnosis.

PMID- 17497663
TI  - Secretory activity in medullary thyroid carcinoma: a cytomorphological and
      immunocytochemical study.
AB  - Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy of C
      cell origin that secretes calcitonin. Although its varied cytomorphologic
      features are well described in literature, very little is mentioned about the
      morphologic manifestation of its secretory activity. This study, based on nine
      fine needle aspiration (FNA) samples from eight MTC patients, is an attempt to
      present the varied cytomorphologic features suggesting secretory activity in MTC
      as observed in Papanicolaou and MGG stained FNA smears and correlate them with
      the immunocytochemical (ICC) staining for calcitonin performed on FNA smears and
      the serum calcitonin values. The average number of cells in these nine samples
      was as follows: oval/triangular/plasmacytoid (56.7%), small round (23.6%),
      spindle-shaped (12.7%), and miscellaneous (7.1%). The cytomorphological features
      suggesting secretory activity, viz., fine cytoplasmic vacuoles, azurophillic
      granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions
      were present in eight, eight, five, and six samples, respectively. Material
      likely to be amyloid, based on morphological features, was present
      extracellularly in three samples and both intracellularly and extracellularly in
      six samples. Immunocytochemically, all the nine samples stained for calcitonin
      and all the three stained for chromogranin showed positive cytoplasmic reaction
      in the neoplstic cells. The background amyloid (in six samples), the coarse
      cytoplasmic granules (in two samples), and the contents of ICL (in one sample)
      were found to be positively stained for calcitonin. The intracytoplasmic
      secretory material appeared to be diffusing out of some cells both in the routine
      MGG stained smears and in the smears stained for calcitonin. Histopathology
      reports of seven samples in six patients confirmed the cytodiagnosis of MTC in
      all. Baseline serum calcitonin values in three cases and postoperative serum
      calcitonin levels during follow-up in three others were high. Thus, our study
      highlighted the morphological manifestations of secretory activity in MTC and the
      nature of secretory material as calcitonin, supported by immunocytochemical
      staining and serum calcitonin level.

PMID- 17497664
TI  - Diagnostic utility of D2-40 and podoplanin in effusion cell blocks.
AB  - The distinction between malignant mesothelioma and adenocarcinoma is a diagnostic
      challenge in cytologic specimens of effusion fluids. As for today, no single
      antibody has demonstrated absolute sensitivity or specificity for Mesothelioma.
      D2-40 and podoplanin have recently been recognized to stain mesothelial cells.
      Our aim for this study was to evaluate the utility of these two markers as
      indicators of mesothelial cells using cell blocks by comparison with two other
      established mesothelial markers. A total of 40 cell blocks of effusion fluids
      including cases of epithelioid mesotheliomas, metastatic carcinomas and benign
      cases with reactive mesothelial cells were selected. A panel of immunostains
      including D2-40, podoplanin, CK5, and calretinin was performed. D2-40 and
      podoplanin were positive in 100% of mesothelioma cases in comparison to
      metastatic adenocarcinoma cases where the positivity was 0%. It is concluded that
      D2-40 and podoplanin are very useful markers for mesotheliomas. Since these
      markers are extremely helpful in differentiating epithelioid mesothelioma from
      metastatic adenocarcinoma, they shall be a valuable addition to the battery of
      markers used to differentiate the two entities.

PMID- 17497665
TI  - Primary Ewing sarcoma/PNET of the kidney: fine-needle aspiration, histology, and
      dual color break apart FISH Assay.
AB  - A 34-year-old previously healthy Hispanic man presented with lower back pain. CT
      scan revealed an 8-cm space-occupying lesion in the superior pole of the left
      kidney with numerous small lytic lesions in the skull, vertebrae, ribs, and
      pelvic bones. CT-guided fine-needle aspiration biopsy revealed a high-grade
      primitive small round cell tumor with the tumor cells being strongly positive for
      CD99 and vimentin. The patient subsequently underwent a left nephrectomy.
      Fluorescence in situ hybridization analysis using a DNA probe for the Ewing
      Sarcoma breakpoint region 1 (EWSR1) on chromosome 22g12 revealed a rearrangement
      of the EWSR1 locus. The diagnosis of primary Ewing sarcoma/primitive
      neuroectodermal tumor of the kidney was established.

PMID- 17497666
TI  - Chaetomium fungal elements in a conventional vaginal smear.

PMID- 17497668
TI  - Sexual dimorphism of G-protein subunit Gng13 expression in the cortical region of
      the developing mouse ovary.
AB  - In our search for genes required for the development and function of mouse
      gonads, we identified Gng13 (guanine nucleotide binding protein 13, gamma), a
      gene with an embryonic expression pattern highly restricted to the ovary. Based
      on reverse transcriptase-polymerase chain reaction (RT-PCR) and whole-mount in
      situ hybridization, Gng13 is expressed in both XX and XY gonads at embryonic day
      (E) 11.5, but becomes up-regulated in the XX gonad by E12.5. Expression is
      retained after treatment with busulfan, a chemical known to eliminate germ cells,
      pointing to the soma as a site of Gng13 transcription. In situ hybridization of
      embryonic ovarian tissue sections further localized the expression to the cortex
      of the developing XX gonad. Gng13 expression in the adult is also highly
      restricted. Northern blot analyses and Genomic Institute of the Novartis Research
      Foundation expression profiling of adult tissues detected very high expression in
      the cerebrum and cerebellum, in addition to, a weaker signal in the ovary. Gng13
      belongs to a well-known family of signal transduction molecules with functions in
      many aspects of development and organ physiology. Here, we report that, in the
      developing mouse embryo, expression of Gng13 mRNA is highly restricted to the
      cortex of the XX gonad during sexual differentiation, suggesting a role for this
      gene during ovarian development.

PMID- 17497667
TI  - Exercise decreases myelin-associated glycoprotein expression in the spinal cord
      and positively modulates neuronal growth.
AB  - To successfully grow, neurons need to overcome the effects of hostile
      environments, such as the inhibitory action of myelin. We have evaluated the
      potential of exercise to overcome the intrinsic limitation of the central nervous
      system for axonal growth. In line with the demonstrated ability of exercise to
      increase the regenerative potential of neurons, here we show that exercise
      reduces the inhibitory capacity of myelin. Cortical neurons grown on myelin from
      exercised rats showed a more pronounced neurite extension compared with neurons
      grown on poly-D-lysine, or on myelin extracted from sedentary animals. The
      activity of cyclin-dependent kinase 5, a kinase involved in neurite outgrowth,
      was found to be increased in cortical neurons grown on exercise-myelin and in the
      lumbar spinal cord enlargement of exercised animals. Exercise significantly
      decreased the levels of myelin-associated glycoprotein (MAG), a potent axonal
      growth inhibitor, suggesting that downregulation of MAG is part of the mechanism
      through which exercise reduces growth inhibition. It is known that exercise
      elevates brain-derived neurotrophic factor (BDNF) spinal cord levels and that
      BDNF acts to overcome the inhibitory effects of myelin. Accordingly, we blocked
      the action of BDNF during exercise, which suppressed the exercise-related MAG
      decrease. Protein kinase A (PKA) has been related to the ability of BDNF to
      overcome growth inhibition; in agreement, we found that exercise increased PKA
      levels and this effect was reverted by blocking BDNF. Overall, these results show
      that exercise promotes a permissive cellular environment for axonal growth in the
      adult spinal cord requiring BDNF action.

PMID- 17497669
TI  - Role of aralar, the mitochondrial transporter of aspartate-glutamate, in brain N
      acetylaspartate formation and Ca(2+) signaling in neuronal mitochondria.
AB  - Aralar, the Ca(2+)-dependent mitochondrial aspartate-glutamate carrier expressed
      in brain and skeletal muscle, is a member of the malate-aspartate NADH shuttle.
      Disrupting the gene for aralar, SLC25a12, in mice has enabled the discovery of
      two new roles of this carrier. On the one hand, it is required for synthesis of
      brain aspartate and N-acetylaspartate, a neuron-born metabolite that supplies
      acetate for myelin lipid synthesis; and on the other, it is essential for the
      transmission of small Ca(2+) signals to mitochondria via an increase in
      mitochondrial NADH.

PMID- 17497670
TI  - Neuroinflammation and regulation of glial glutamate uptake in neurological
      disorders.
AB  - Oxidative stress, neuroinflammation, and excitotoxicity are frequently considered
      distinct but common hallmarks of several neurological disorders, including
      Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and
      Alzheimer's disease. Although neuron degeneration and death are the ultimate
      consequences of these pathological processes, it is now widely accepted that
      alterations in the function of surrounding glial cells are key features in the
      progression of these diseases. In response to alteration in their local
      environment, microglia, commonly considered the resident immune cells of the
      nervous parenchyma, become activated and release a variety of soluble factors.
      Among these, proinflammatory cytokines and free radicals actively participate in
      the degenerative insults. In addition, excitotoxic neuronal damage resulting from
      excessive glutamate is frequently associated with impaired handling of
      extracellular glutamate by gliotic astrocytes. Although several research projects
      have focused on the biochemical mechanisms of the regulation of glial glutamate
      transporters, a relationship between activation of microglia and modulation of
      astrocytic glutamate uptake is now suggested. The aim of this review is to
      summarize and discuss the data showing an influence of inflammatory mediators and
      related free radicals on the expression and activity of glial glutamate
      transporters.

PMID- 17497671
TI  - Bone marrow-derived very small embryonic-like stem cells: their developmental
      origin and biological significance.
AB  - Data from our and other laboratories provide evidence that bone marrow (BM)
      contains a population of stem cells that expresses early developmental markers
      such as (1) stage-specific embryonic antigen (SSEA) and (2) transcription factors
      Oct-4 and Nanog. These are the markers characteristic for embryonic stem cells,
      epiblast stem cells, and primordial germ cells (PGC). The presence of these stem
      cells in adult BM supports the concept that this organ contains some population
      of pluripotent stem cells that is deposited in embryogenesis during early
      gastrulation. We hypothesize that these cells could be direct descendants of the
      germ lineage that, to pass genes on to the next generations, has to create soma
      and, thus, becomes a "mother lineage" for all somatic cell lineages present in
      the adult body. Germ potential is established after conception in totipotent
      zygotes and retained in blastomeres of morula, cells from the inner cell mass of
      blastocyst, epiblast, and population of PGC. We will present a concept that
      SSEA(+) Oct-4(+) Nanog(+) cells identified in BM could be descendants of epiblast
      cells as well as some rare migrating astray PGC.

PMID- 17497672
TI  - Macrophage contribution to the response of the rat organ of Corti to amikacin.
AB  - Transdifferentiation of nonsensory supporting cells into sensory hair cells
      occurs naturally in the damaged avian inner ear. Such transdifferentiation was
      achieved experimentally in the cochlea of deaf guinea pigs through Atoh 1 gene
      transfection. Supporting cells may therefore serve as targets for
      transdifferentiation therapy. Supporting cells rapidly degenerate after hair cell
      disappearance, however, limiting the therapeutic window for gene transfer. We
      studied the time course of ultrastructural and phenotypical changes occurring in
      Deiters cells (hair cell supporting cells) after ototoxic treatment in the rat.
      The presence of macrophages in the cochlea was also investigated, to study any
      deleterious effects they may have on pathologic tissues. One week after treatment
      most hair cells had disappeared. Deiters cells no longer expressed the glial
      marker vimentin but instead displayed typical hair cell markers, the calcium
      binding proteins calbindin and parvalbumin. This suggests that a process of
      transdifferentiation of Deiters cells into hair cells was activated. By 3 weeks
      post-treatment, however, the Deiters cells began to degenerate and by 10 weeks
      post-treatment the organ of Corti was degraded fully. Interestingly, a marked
      increase in macrophage density was seen after the end of amikacin treatment to 10
      weeks post-treatment. This suggests chronic inflammation is involved in
      epithelium degeneration. Consequently, early treatments with anti-inflammatory
      factors might promote supporting cell survival, thus improving the efficacy of
      more specific strategies aimed to regenerate hair cells from nonsensory cells.

PMID- 17497673
TI  - Decreased focal inflammatory response by G-CSF may improve stroke outcome after
      transient middle cerebral artery occlusion in rats.
AB  - Recent studies have shown that administration of granulocyte colony-stimulating
      factor (G-CSF) is neuroprotective. However, the precise mechanisms of the
      neuroprotective effect of G-CSF are not entirely known. We carried out 90-min
      transient middle cerebral occlusion (tMCAO) of rats. The rats were injected with
      vehicle or G-CSF (50 mug/kg) immediately after reperfusion and sacrificed 8, 24,
      or 72 hr later. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was carried
      out using brain sections of 72 hr, and immunohistochemistry was carried out with
      those of 8, 24, and 72 hr. TTC-staining showed a significant reduction of infarct
      volume in the G-CSF-treated group (**P < 0.01). Immunohistochemistry showed a
      significant decrease of the number of cells expressing tumor necrosis factor
      alpha (TNF-alpha) at 8-72 hr, transforming growth factor-beta (TGF-beta) and
      inducible nitric oxide synthase (iNOS) at 24 and 72 hr after tMCAO in the peri
      ischemic area (*P < 0.05 each). Our data suggest that the suppression of
      inflammatory cytokines and iNOS expression may be one mechanism of
      neuroprotection by G-CSF.

PMID- 17497674
TI  - Glial cell line-derived neurotrophic factor protects astrocytes from
      staurosporine- and ischemia- induced apoptosis.
AB  - Glial cell line-derived neurotrophic factor (GDNF) promotes the survival and
      functions of neurons. It has been shown to be a promising candidate in the
      treatment of ischemia and other neurodegenerative diseases. We transfected mouse
      astrocytes in primary cultures with a human GDNF gene and found that their
      conditioned medium could not only support the growth and survival of cultured
      dopaminergic neurons but also protect astrocytes from staurosporine- and ischemia
      induced apoptosis. This indicated that these transfected astrocytes could release
      GDNF. A similar protective effect on astrocytes against apoptosis was evident
      when recombinant human GDNF was used. Moreover, GDNF reduced caspase-3 activity
      but not that of caspase-1 in cultured astrocytes after ischemia treatment. Thus,
      GDNF protects astrocytes from apoptosis by inhibiting the activation of caspase
      3.

PMID- 17497675
TI  - Among the branched-chain amino acids, only valine metabolism is up-regulated in
      astrocytes during glutamate exposure.
AB  - Glutamate homeostasis during glutamatergic neurotransmission is predominantly
      maintained via functioning of the glutamate-glutamine cycle. However, the
      glutamate-glutamine cycle explains only the fate of the carbon atoms but not that
      of the accompanying transfer of nitrogen from neurons to astrocytes. In this
      respect, a putative branched-chain amino acid (BCAA) shuttle has been suggested
      for transfer of amino nitrogen. Metabolism of BCAAs was investigated in cultured
      cerebellar astrocytes in a superfusion paradigm employing (15)N-labeled leucine,
      isoleucine, or valine. Some cultures were exposed to pulses of glutamate (50
      microM; 10 sec every 2 min; 75 min in total) to mimic conditions during
      glutamatergic synaptic activity. (15)N labeling of glutamate, aspartate,
      glutamine, alanine, and the three BCAAs was determined by using mass
      spectrometry. Incorporation of (15)N into intracellular glutamate from
      [(15)N]leucine, [(15)N]isoleucine, or [(15)N]valine amounted to about 40-50% and
      differed only slightly among the individual BCAAs. Interestingly, label (%) in
      glutamate from [(15)N]valine was not decreased upon exposure to exogenous
      glutamate, which was in contrast to a marked decrease in labeling (%) from
      [(15)N]leucine or [(15)N]isoleucine. This suggests an up-regulation of
      transamination involving only valine during repetitive exposure to glutamate. It
      is suggested that valine in particular might have an important function as an
      amino acid translocated between neuronal and astrocytic compartments, a function
      that might be up-regulated during synaptic activity.

PMID- 17497676
TI  - The use of conformation-specific ligands and assays to dissect the molecular
      mechanisms of neurodegenerative diseases.
AB  - The use of conformation-specific ligands has been closely linked to progress in
      the molecular characterization of neurodegenerative diseases. Deposition of
      misfolded or misprocessed proteins is now recognized as a hallmark of all
      neurodegenerative diseases. Initially, dyes like Congo red and thioflavin T were
      used as crudely conformation-specific ligands for staining the beta-sheeted
      protein components of amyloid deposits in neurodegenerative diseases such as
      Alzheimer disease (AD) and prion disease, the two diseases in which protein
      conformations were distinguished early on. This conformational characterization
      of extracellular protein deposits with dyes ultimately led to the identification
      of key players in the disease processes. The recent discovery of intermediate
      conformational species, i.e., soluble oligomers for AD and PK-sensitive PrP(Sc)
      for prion disease, whose conformation and assembly are thought to be distinct
      from both the physiological and the fibrillar conformational states, replaced the
      former notion that the microscopic protein deposits themselves caused disease.
      This insight and the generation of conformation-specific monoclonal antibodies to
      these conformers further advanced diagnosis and the understanding of molecular
      mechanisms of AD and are likely to do so in other neurodegenerative diseases.
      Here we review how conformer distinction performed by a variety of different
      techniques, including biophysical, biochemical, and antibody-based methods, led
      to the current molecular concepts of AD and the prion diseases. We provide an
      outlook on the application of these techniques in advancing the understanding of
      molecular mechanisms of other neurodegenerative diseases or degenerative brain
      conditions.

PMID- 17497677
TI  - Hyperthermia inhibits cell proliferation and induces apoptosis: relative
      signaling status of P53, S100A4, and Notch in heat sensitive and resistant cell
      lines.
AB  - The effects of hyperthermia on the expression of p53, the apoptosis-associated
      genes Bax and Bcl-2, Notch and S100A4 have been studied in the HepG2 cell line
      and the HUT cell line derived from HepG2, adapted for growth in hyperthermic
      conditions. Hyperthermia inhibits cell proliferation and induces apoptosis. HepG2
      and HUT cells differed in respect of anchorage to growth surface, degree of
      proliferation and apoptosis and expression of p53, Bax, Bcl-2, Notch, and S100A4
      genes. The induction of apoptosis and the inhibition of cell proliferation
      occurred independently of p53, and independently also of involvement of the
      apoptosis family genes Bax and Bcl-2. We demonstrate novel and marked differences
      between transient heat shock and heat adaptation in respect of pathways of
      signaling and generation of phenotypic effects in vitro. Different signaling
      patterns have been identified here. Pathways of signaling by S100A4, by its
      interaction with and sequestration of p53, and by Notch also seem differentially
      operational in the induction of apoptosis, and both appear to be activated as
      alternative pathways in the context of hyperthermia signaling independently of
      p53.

PMID- 17497678
TI  - Runx2 determines bone maturity and turnover rate in postnatal bone development
      and is involved in bone loss in estrogen deficiency.
AB  - Runx2 is an essential transcription factor for osteoblast differentiation.
      However, the functions of Runx2 in postnatal bone development remain to be
      clarified. Introduction of dominant-negative (dn)-Runx2 did not inhibit Col1a1
      and osteocalcin expression in mature osteoblastic cells. In transgenic mice that
      expressed dn-Runx2 in osteoblasts, the trabecular bone had increased
      mineralization, increased volume, and features of compact bone, and the
      expression of major bone matrix protein genes was relatively maintained. After
      ovariectomy, neither osteolysis nor bone formation was enhanced and bone was
      relatively conserved. In wild-type mice, Runx2 was strongly expressed in immature
      osteoblasts but downregulated during osteoblast maturation. These findings
      indicate that the maturity and turnover rate of bone are determined by the level
      of functional Runx2 and Runx2 is responsible for bone loss in estrogen
      deficiency, but that Runx2 is not essential for maintenance of the expression of
      major bone matrix protein genes in postnatal bone development and maintenance.

PMID- 17497679
TI  - Optimization of microencapsulated recombinant CHO cell growth, endostatin
      production, and stability of microcapsule in vivo.
AB  - Microencapsulation of recombinant cells secreting endostatin offers a promising
      approach to tumor gene therapy in which therapeutic protein is delivered in a
      sustainable and long-term fashion by encapsulated recombinant cells. However, the
      studies of cell growth and protein production in vivo are very limited. In this
      study, the effects of microencapsulation parameters on in vivo cell growth,
      endostatin production, and microcapsule stability after implantation in the
      peritoneal cavity of mice were for the first time investigated. Microcapsules
      with liquid core reached higher cell density and endostatin production at day 18
      than microcapsules with solid core. There was no significant difference in
      stability whether the core of the microcapsule was solid or liquid. Decrease in
      microcapsule size increased the stability of microcapsule. The microcapsules kept
      intact in the peritoneal cavity of mice after 36 days of implantation when the
      microcapsules size was 240 microm in diameter, which gave rise to high endostatin
      production as well. The optimized microencapsulation conditions for in vivo
      implantation are liquid core and 240 microm in diameter. This study provides
      useful information for antiangiogenic gene therapy to tumors using
      microencapsulated recombinant cells.

PMID- 17497680
TI  - Nitric oxide-releasing polyurethane-PEG copolymer containing the YIGSR peptide
      promotes endothelialization with decreased platelet adhesion.
AB  - Thrombosis and intimal hyperplasia are the principal causes of small-diameter
      vascular graft failure. To improve the long-term patency of polyurethane vascular
      grafts, we have incorporated both poly(ethylene glycol) and a diazeniumdiolate
      nitric oxide (NO) donor into the backbone of polyurethane to improve
      thromboresistance. Additionally, we have incorporated the laminin-derived cell
      adhesive peptide sequence YIGSR to encourage endothelial cell adhesion and
      migration, while NO release encourages endothelial cell proliferation. NO
      production by polyurethane films under physiological conditions demonstrated
      biphasic release, in which an initial burst of 70% of the incorporated NO was
      released within 2 days, followed by sustained release over 2 months. Endothelial
      cell proliferation in the presence of the NO-releasing material was increased as
      compared to control polyurethane, and platelet adhesion to polyethylene glycol
      containing polyurethane was decreased significantly with the addition of the NO
      donor.

PMID- 17497681
TI  - Modeling of water absorption induced cracks in resin-based composite supported
      ceramic layer structures.
AB  - Cracking patterns in the top ceramic layers of the modeled dental multilayers
      with polymer foundation are observed when they are immersed in water. This
      article developed a model to understand this cracking mechanism. When water
      diffuses into the polymer foundation of dental restorations, the foundation will
      expand; as a result, the stress will build up in the top ceramic layer because of
      the bending and stretching. A finite element model based on this mechanism is
      built to predict the stress build-up and the slow crack growth in the top ceramic
      layers during the water absorption. Our simulations show that the stress build-up
      by this mechanism is high enough to cause the cracking in the top ceramic layers
      and the cracking patterns predicted by our model are well consistent with those
      observed in experiments on glass/epoxy/polymer multilayers. The model is then
      used to discuss the life prediction of different dental ceramics.

PMID- 17497682
TI  - The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and
      zebrafish in vivo.
AB  - Angiogenesis plays an important role in a wide range of physiological processes
      such as wound healing and fetal development. Many diseases are associated with
      imbalances in regulation of angiogenesis, in which it is either excessive or
      there is insufficient blood vessel formation. Angelica sinensis (AS), commonly
      used in the prescriptions of Chinese medicine, is a potential candidate for
      curing such diseases. However, biological effects of AS on angiogenesis and
      underlying mechanisms are yet to be fully elucidated. This investigation
      describes the angiogenic effects of AS extract on human endothelial cells (HUVEC)
      in vitro and zebrafish in vivo. The extract was demonstrated, by XTT assay and
      microscopic cell counting, to stimulate the proliferation of HUVEC; in addition,
      flow cytometry analysis indicated that the extract increased the percentage of
      HUVEC in the S phase. The wound healing migration assay illustrated that a
      dramatic increase in migration could be measured in AS extract-treated HUVEC.
      Meanwhile, the number of invaded cells and the mean tube length were
      significantly increased in AS extract treatment groups. The extract was also
      demonstrated to promote changes in subintestinal vessels (SIVs) in zebrafish, one
      feature of angiogenesis. In addition, AS extract was found by real-time PCR to
      enhance vascular endothelial growth factor (VEGF) mRNA expression. In a bead
      based immunoassay, higher levels of p38 and JNK 1/2 expression were also observed
      in effusions compared with control cells. All results suggest that Angelica
      sinensis extract can promote angiogenesis, and that the angiogenic effects
      involve p38 and JNK 1/2 phosphorylation.

PMID- 17497683
TI  - Profiling of mitochondrial associated proteins from rat colon.
AB  - Mitochondrial dysfunction, damage and mutations of mitochondrial proteins give
      rise to a range of ill understood patterns of disease. Although there is
      significant general knowledge of the proteins and the functional processes of the
      mitochondria, there is little knowledge of difference about how mitochondria
      respond and how they are regulated in different organs and tissues. Proteomic
      profiling of mitochondria and associated proteins involved in mitochondrial
      regulation and trafficking within cells and tissues has the potential to provide
      insights into mitochondrial dysfunction associated with many human diseases. The
      rat colon mitoproteome analysis presented here provides a useful tool to assist
      in identification and interpretation of mitochondrial dysfunction implicated in
      colon pathogenesis. 2DPAGE followed by LC/MS/MS was used to identify 430 proteins
      from mitochondrial enriched fractions prepared from rat colon, resulting in 195
      different proteins or approximately 50% of the resolved proteins being identified
      as multiple protein expression forms. Proteins associated with the colon
      mitoproteome were involved in calcium binding, cell cycle, energy metabolism and
      electron transport chain, protein folding, protein synthesis and degradation,
      redox regulation, structural proteins, signalling and transporter and channel
      proteins. The mitochondrial associated proteins identified in this study of colon
      tissue complement and are compared with other recently published mitoproteome
      analyses from other organ tissues, and will assist in revealing potentially organ
      specific roles of the mitochondria and organ specific disease associated with
      mitochondrial dysfunction.

PMID- 17497684
TI  - New objective measurement to characterize the porosity of textile implants.
AB  - The inflammatory and fibrotic intensity of a foreign body reaction largely
      depends on the porosity of the implanted material. Furthermore, the size of the
      pore and its geometry define the capability to allow tissue ingrowth. We present
      an image analysis system, which allows objectifying in two dimensions the pores'
      structure and geometry of textile fabrics, that are used to reinforce the
      abdominal wall or pelvic floor. The porosity of the textile is measured at four
      samples with differences in structure. The porosity decreases markedly if foreign
      body response is considered, leading to the definition of an "effective
      porosity". Because of the high stiffness of the polymer fibers the elasticity of
      textile implants usually result from a deformation of the pores, leading to a
      marked reduction of the effective porosity if a mechanical stress is applied.
      Further in vivo studies have to investigate, whether the preservation of a high
      effective porosity under stress may help to improve biocompatibility of textile
      implants.

PMID- 17497685
TI  - Alterations of human acellular tissue matrix by gamma irradiation: histology,
      biomechanical property, stability, in vitro cell repopulation, and remodeling.
AB  - AlloDerm, a processed acellular human tissue matrix, is used in a number of
      surgical applications for tissue repair and regeneration. In the present work,
      AlloDerm serves as a model system for studying gamma radiation-induced changes in
      tissue structure and stability as well as the effect of such changes on the cell
      matrix interactions, including cell repopulation and matrix remodeling. AlloDerm
      tissue matrix was treated with 2-30 kGy gamma irradiation at room temperature.
      Gamma irradiation reduced the swelling of tissue matrix upon rehydration and
      caused significant structural modifications, including collagen condensation and
      hole formation in collagen fibres. The tensile strength of AlloDerm increased at
      low gamma dose but decreased with increasing gamma dosage. The elasticity of
      irradiated AlloDerm was reduced significantly. Calorimetric study showed that
      gamma irradiation destabilized the tissue matrix, resulting in greater
      susceptibility to proteolytic enzyme degradation. Although gamma irradiation did
      not affect in vitro proliferation of fibroblast cells, it promoted tissue
      degradation upon cell repopulation and influenced synthesis and deposition of new
      collagen.

PMID- 17497686
TI  - Substrate adhesion affects contraction and mechanical properties of fibroblast
      populated collagen lattices.
AB  - Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure.
      The purpose of this study was to evaluate the effect of substrate adhesion on the
      contraction and mechanical properties of fibroblast populated collagen lattices.
      Bacteriological grade polystyrene (BGPS) plates and tissue culture polystyrene
      (TCPS) plates were used as substrates for incubation of fibroblast populated
      collagen lattices. Hydrophobicity of the polystyrene surfaces was measured by the
      static sessile contact angle method. Collagen lattice contraction was recorded
      for 2 weeks, after which the lattices were mechanically tested. The BGPS culture
      plate had a significantly larger contact angle and was more hydrophobic than the
      TCPS culture plate. Both hydrophobicity and peripheral detachment of the collagen
      gel significantly decreased the time lag before initiation of gel contraction and
      increased the strength of the fibroblast populated collagen lattices. Substrate
      adhesion affects the contractility and strength of cell seeded collagen gels.
      This information may be useful in developing tissue engineered tendons and
      ligaments.

PMID- 17497687
TI  - Ascidian notochord morphogenesis.
AB  - The development of the notochord involves a complex set of cellular behaviors.
      While these morphogenic behaviors are common to all chordates, the ascidian
      provides a particularly attractive experimental model because of its relative
      simplicity. In particular, all notochord morphogenesis in ascidians takes place
      with only 40 cells, as opposed to the hundreds of cells in vertebrate model
      systems. Initial steps in ascidian notochord development convert a monolayer of
      epithelial-like cells in the pregastrula embryo to a cylindrical rod of single
      cell diameter. Convergent extension is responsible for the intercalation of
      notochord cells and some degree of notochord elongation, while a second phase of
      elongation is observed as the notochord narrows medially and increases in volume.
      The mechanism by which the volume of the notochord increases differs between
      ascidian species. Some ascidians produce extracellular pockets that will
      eventually coalesce to form a lumen running the length of the notochord; whereas
      others do not. By either mechanism, the resulting notochord serves as a
      hydrostatic skeleton allowing for the locomotion of the swimming larva. Several
      basic cell behaviors, such as cell shape changes, cell rearrangement,
      establishment of cell polarity, and alteration of extracellular environment, are
      displayed in the process of notochord morphogenesis. Modern analysis of ascidian
      notochord morphogenesis promises to contribute to our understanding of these
      fundamental biological processes.

PMID- 17497688
TI  - Editorial on segmentation focus.

PMID- 17497689
TI  - Sharp developmental thresholds defined through bistability by antagonistic
      gradients of retinoic acid and FGF signaling.
AB  - The establishment of thresholds along morphogen gradients in the embryo is poorly
      understood. Using mathematical modeling, we show that mutually inhibitory
      gradients can generate and position sharp morphogen thresholds in the embryonic
      space. Taking vertebrate segmentation as a paradigm, we demonstrate that the
      antagonistic gradients of retinoic acid (RA) and Fibroblast Growth Factor (FGF)
      along the presomitic mesoderm (PSM) may lead to the coexistence of two stable
      steady states. Here, we propose that this bistability is associated with abrupt
      switches in the levels of FGF and RA signaling, which permit the synchronized
      activation of segmentation genes, such as mesp2, in successive cohorts of PSM
      cells in response to the segmentation clock, thereby defining the future
      segments. Bistability resulting from mutual inhibition of RA and FGF provides a
      molecular mechanism for the all-or-none transitions assumed in the "clock and
      wavefront" somitogenesis model. Given that mutually antagonistic signaling
      gradients are common in development, such bistable switches could represent an
      important principle underlying embryonic patterning.

PMID- 17497690
TI  - Synaptosome behaviour is unaffected by weak pulsed electromagnetic fields.
AB  - The present study examined the effect on rat cortical synaptosomes of a 2 h
      exposure to 50-Hz electromagnetic fields (EMFs) with a peak magnetic field of 2
      mT. We measured modifications of synaptosomal mitochondrial respiration rate, ATP
      production, membrane potential, intrasynaptosomal Ca(2+) concentration and free
      iron release. The O(2) consumption remained unvaried in exposed synaptosomes at
      about 2 nM O(2)/min/mg proteins; ATP production was also unchanged. The
      intrasynaptosomal Ca(2+) concentration decreased slowly and there was a slight,
      but non-significant, depolarisation of the synaptosomal membrane. Finally, the
      free iron release by synaptosomal suspensions, a useful predictor of neuro
      developmental outcome, remained unchanged after EMF exposure. On the whole, our
      results indicate that the physiological behaviour of cortical synaptosomes is not
      affected by weak pulsed EMFs.

PMID- 17497691
TI  - Continuous culture of two lancelets and production of the second filial
      generations in the laboratory.
AB  - The lancelet is considered to be a promising laboratory model animal. To
      establish laboratory colonies of lancelet, we collected parental lancelets of
      Branchiostoma belcheri and B. japonicum (previously named as B. belcheri
      tsingtauense) with fully developed gonads from Xiamen Rare Marine Creature
      Conservation Areas (Fujian, China) on dates just before their spawning in the
      field in 2005. Those parental lancelets spawned spontaneously in the laboratory
      and produced thousands upon thousands of fertilized eggs. After carefully
      hatching and maintaining for almost 1 year, we successfully obtained about 500
      first generation (F1) adults of B. belcheri and 3,300 of B. japonicum. Part of
      those F1 lancelets ripened and spontaneously spawned in 2006, and several
      thousands of second generation (F2) individuals of both species were produced.
      The young F2 lancelets are growing in good condition and some of B. japonicum
      initiated gonad development in December, 2006. Our experience emphasizes that
      cleanness of settlement substratum and sufficient food supply are important
      factors for long-term culture of lancelets in the laboratory.

PMID- 17497692
TI  - BMP7 promotes adipogenic but not osteo-/chondrogenic differentiation of adult
      human bone marrow-derived stem cells in high-density micro-mass culture.
AB  - The objective of our study was to elucidate the potential of bone morphogenetic
      protein-7 (BMP7) to initiate distinct mesenchymal lineage development of human
      adult mesenchymal stem cells (MSC) in three-dimensional micro-mass culture.
      Expanded MSC were cultured in high-density micro-masses under serum-free
      conditions that favor chondrogenic differentiation and were stimulated with 50
      200 ng/ml BMP7 or 10 ng/ml transforming growth factor-beta3 (TGFbeta3) as
      control. Histological staining of proteoglycan with alcian blue, mineralized
      matrix according to von Kossa, and lipids with Oil Red O, immunostaining of type
      II collagen as well as real-time gene expression analysis of typical
      chondrogenic, adipogenic, and osteogenic marker genes showed that BMP7 promoted
      adipogenic differentiation of MSC. Micro-masses stimulated with BMP7 developed
      adipocytic cells filled with lipid droplets and showed an enhanced expression of
      the adipocyte marker genes fatty acid binding protein 4 (FABP4) and the adipose
      most abundant transcript 1 (apM1). Development along the chondrogenic lineage or
      stimulation of osteogenic differentiation were not evident upon stimulation with
      BMP7 in different concentrations. In contrast, TGFbeta3 directed MSC to form a
      cartilaginous matrix that is rich in proteoglycan and type II collagen. Gene
      expression analysis of typical chondrocyte marker genes like cartilage oligomeric
      matrix protein (COMP), link protein, aggrecan, and types IIalpha1 and IXalpha3
      collagen confirmed chondrogenic differentiation of MSC treated with TGFbeta3.
      These results suggest that BMP7 promotes the adipogenic and not the osteogenic or
      chondrogenic lineage development of human stem cells when assembled three
      dimensionally in micro-masses.

PMID- 17497693
TI  - Farming and the prevalence of non-reversible airways obstruction: results from a
      population-based study.
AB  - INTRODUCTION: Occupational exposure to noxious dusts, gases, and fumes most
      likely contributes to obstructive lung disease. We studied whether self-reported
      farming work is associated with non-reversible airways obstruction. METHODS:
      Following the burden of obstructive lung disease (BOLD) study protocol, we
      surveyed a gender-stratified population-based sample of 2,200 adults aged 40
      years and over. Pre- and post-bronchodilator spirometry, as well as information
      on smoking, occupation, and reported respiratory disease was recorded. According
      to GOLD criteria, non-reversible airways obstruction was defined as a post
      bronchodilator forced expiratory volume (FEV(1))/forced vital capacity (FVC) <
      0.70. Occupational and smoking history was based on questionnaire. Farming was
      defined as ever working in this occupation for 3 months or longer. RESULTS: For
      1,258 participants with complete data (post-bronchodilator spirometry and
      questionnaire data), 288 (=22.9%) reported farming. Among the 288 participants
      reporting farming, the prevalence of non-reversible airways obstruction was
      30.2%. Farming was significantly associated with airways obstruction: chronic
      obstructive pulmonary disease (COPD) GOLD stage I or higher (OR 1.5; 95% CI 1.1
      2.0) and COPD GOLD stage II or higher (OR 1.8; 95% CI 1.2-2.7). The latter
      estimate was unchanged when adjustment for competing risks gender, age, and
      smoking was done. In this population the risk for non-reversible airways
      obstruction attributable to farming was 7.7%. CONCLUSION: Farming should be
      considered a risk factor for non-reversible airways obstruction.

PMID- 17497695
TI  - Developmental characteristics of AMPA receptors in chick lumbar motoneurons.
AB  - Ca2+ fluxes through ionotropic glutamate receptors regulate a variety of
      developmental processes, including neurite outgrowth and naturally occurring cell
      death. In the CNS, NMDA receptors were originally thought to be the sole source
      of Ca2+ influx through glutamate receptors; however, AMPA receptors also allow a
      significant influx of Ca2+ ions. The Ca2+ permeability of AMPA receptors is
      regulated by the insertion of one or more edited GluR2 subunits. In this study,
      we tested the possibility that changes in GluR2 expression regulate the Ca2+
      permeability of AMPA receptors during a critical period of neuronal development
      in chick lumbar motoneurons. GluR2 expression is absent between embryonic day (E)
      5 and E7, but increases significantly by E8 in the chick ventral spinal cord.
      Increased GluR2 protein expression is correlated with parallel changes in GluR2
      mRNA in the motoneuron pool. Electrophysiological recordings of kainate-evoked
      currents indicate a significant reduction in the Ca2(+)-permeability of AMPA
      receptors between E6 and E11. Kainate-evoked currents were sensitive to the AMPA
      receptor blocker GYKI 52466. Application of AMPA or kainate generates a
      significant increase in the intracellular Ca2+ concentration in E6 spinal
      motoneurons, but generates a small response in older neurons. Changes in the
      Ca(2+)-permeability of AMPA receptors are not mediated by age-dependent changes
      in the editing pattern of GluR2 subunits. These findings raise the possibility
      that Ca2+ influx through Ca(2+)-permeable AMPA receptors plays an important role
      during early embryonic development in chick spinal motoneurons.

PMID- 17497694
TI  - From segment to somite: segmentation to epithelialization analyzed within
      quantitative frameworks.
AB  - One of the most visually striking patterns in the early developing embryo is
      somite segmentation. Somites form as repeated, periodic structures in pairs along
      nearly the entire caudal vertebrate axis. The morphological process involves
      short- and long-range signals that drive cell rearrangements and cell shaping to
      create discrete, epithelialized segments. Key to developing novel strategies to
      prevent somite birth defects that involve axial bone and skeletal muscle
      development is understanding how the molecular choreography is coordinated across
      multiple spatial scales and in a repeating temporal manner. Mathematical models
      have emerged as useful tools to integrate spatiotemporal data and simulate model
      mechanisms to provide unique insights into somite pattern formation. In this
      short review, we present two quantitative frameworks that address the
      morphogenesis from segment to somite and discuss recent data of segmentation and
      epithelialization.

PMID- 17497696
TI  - Effects of locomotor stimulation and protein synthesis inhibition on circadian
      rhythms in size changes of L1 and L2 interneurons in the fly's visual system.
AB  - Axons of monopolar cell interneurons L1 and L2 in the first optic lobe (lamina)
      of the fly Musca domestica undergo cyclical changes in diameter. These axons
      swell during the day and shrink during the night. In addition, the axons' size
      depends on light conditions since they are largest in continuous light (LL),
      somewhat smaller under day/night (LD) conditions, and smallest under constant
      darkness (DD). In this study we found that sizes of both cells can further
      increase in free flying flies under LD conditions, while the visual stimulation
      alone does not have significant effect on the cross-sectional area of L1 and L2
      axons. The stimulation of free flying had no effect on L1 and L2 sizes if it was
      performed at the beginning of subjective day in LL or DD. Our results indicate
      that a maximal increase in size of L1 and L2 is observed when stimulation of free
      flying is synchronized with a fly' daily peak of activity. We also found that
      protein synthesis is needed to increase size of monopolar cell axons during the
      day when they normally swell.

PMID- 17497697
TI  - Critical and sensitive periods for reversing the effects of mechanosensory
      deprivation on behavior, nervous system, and development in Caenorhabditis
      elegans.
AB  - In these studies the nematode Caenorhabditis elegans was used as a model to
      investigate ways to reverse the effects of mechanosensory deprivation on behavior
      and development. Rose et al. (J Neurosci 2005; 25:7159-7168) showed that worms
      reared in isolation responded significantly less to a mechanical tap stimulus,
      were significantly smaller, and expressed significantly lower levels of a
      postsynaptic glutamate receptor subunit on the command interneurons of the tap
      response circuit and a presynaptic vesicle marker in the tap sensory neurons
      compared with worms raised in groups. Here, brief mechanical stimulation at any
      time throughout development reversed the effects of isolation on the response to
      tap and on postsynaptic glutamate receptor expression on the command
      interneurons, suggesting there is no critical period for these measures. In
      contrast to the high level of plasticity in glutamate receptor subunit expression
      on the interneurons, low levels of stimulation only rescued vesicle expression in
      the tap sensory neurons early in development and progressively higher levels of
      stimulation were required as the worm developed, suggesting a sensitive period
      immediately after hatching, followed by a period of decreasing plasticity.
      Stimulation during the first three stages of larval development, but not later,
      rescued the effects of isolation on worm length, suggesting there is a critical
      period for this measure that ends in the third larval stage. These results
      indicate that different effects of early isolation required different amounts
      and/or timing of stimulation to be reversed.

PMID- 17497698
TI  - Occupational asbestos exposure among respiratory cancer patients in Lithuania.
AB  - BACKGROUND: Despite intensive use of asbestos, no cancer case has ever been
      diagnosed as asbestos related in Lithuania. This paper attempts to estimate the
      proportion of those occupationally exposed to asbestos among respiratory cancer
      patients. MATERIAL AND METHODS: Occupational exposure to asbestos was assessed
      retrospectively for 298 lung cancer and four mesothelioma patients, admitted to
      the Institute of Oncology, Vilnius. The evaluation was based on personal
      interview data using an internationally established questionnaire covering most
      likely activities of asbestos exposure at the workplace. Cumulative exposure to
      asbestos at work was estimated in fiber years. Lung tissue asbestos fiber burden
      analysis was conducted by scanning transmission electron microscopy on 23
      samples. RESULTS: A cumulative asbestos exposure of > or =25 fiber years was
      found for 10 lung cancer patients (3.4%). They worked in foundries, construction,
      installation, shipyard, power plant, railway, asbestos cement, glass and chemical
      industry. In a further 56 lung cancer patients (18.8%) and for one (25%)
      mesothelioma patient, a cumulative exposure from 5 to 24.9 fiber years was
      assessed. Asbestos fibers were detected in 18 cases, the burden ranged from 0.1
      to 4.1 million fibers/g dry lung tissue; concentrations exceeding 1 million f/g
      dry lung tissue were found in four cases. All fibers were chrysotile.
      CONCLUSIONS: Findings indicate that a fraction (3.4%) of the lung cancer cases
      could be attributed to heavy occupational exposure to asbestos using the Helsinki
      criterion of > or =25 fiber years. Therefore, approximately 50 lung cancer cases
      per year in Lithuania could be asbestos-related compensable occupational
      diseases.

PMID- 17497699
TI  - Abnormal vertebral segmentation and the notch signaling pathway in man.
AB  - Abnormal vertebral segmentation (AVS) in man is a relatively common congenital
      malformation but cannot be subjected to the scientific analysis that is applied
      in animal models. Nevertheless, some spectacular advances in the cell biology and
      molecular genetics of somitogenesis in animal models have proved to be directly
      relevant to human disease. Some advances in our understanding have come through
      DNA linkage analysis in families demonstrating a clustering of AVS cases, as well
      as adopting a candidate gene approach. Only rarely do AVS phenotypes follow clear
      Mendelian inheritance, but three genes-DLL3, MESP2, and LNFG-have now been
      identified for spondylocostal dysostosis (SCD). SCD is characterized by extensive
      hemivertebrae, trunkal shortening, and abnormally aligned ribs with points of
      fusion. In familial cases clearly following a Mendelian pattern, autosomal
      recessive inheritance is more common than autosomal dominant and the genes
      identified are functional within the Notch signaling pathway. Other genes within
      the pathway cause diverse phenotypes such as Alagille syndrome (AGS) and CADASIL,
      conditions that may have their origin in defective vasculogenesis. Here, we deal
      mainly with SCD and AGS, and present a new classification system for AVS
      phenotypes, for which, hitherto, the terminology has been inconsistent and
      confusing.

PMID- 17497700
TI  - Evidence that PI3K, Rac, Rho, and Rho kinase are involved in basic fibroblast
      growth factor-stimulated fibroblast-Collagen matrix contraction.
AB  - Fibroblast-collagen matrix contraction has been used as a model system to study
      how cells organize connective tissue. Previous work showed that lysophosphatidic
      acid (LPA)-stimulated floating collagen matrix contraction is independent of Rho
      kinase while platelet-derived growth factor (PDGF)-stimulated contraction is Rho
      kinase-dependent. The current studies were carried out to determine the signaling
      mechanisms of basic fibroblast growth factor (bFGF)-stimulated fibroblast
      collagen matrix contraction. Both bFGF and LPA promoted equally collagen matrix
      contraction well. Three different inhibitors, LY294002 for phosphatidylinositol-3
      kinase (PI3K), C3 exotransferase for Rho and Y27632 for Rho kinase, suppressed
      the bFGF-stimulated fibroblast-collagen matrix contraction. With bFGF
      stimulation, fibroblasts spread with prominent stress fiber network formation and
      focal adhesions. In the presence of Rho kinase inhibitor, focal adhesions and
      stress fibers were mostly lost. We demonstrated that bFGF stimulation for
      fibroblast caused transient Rac and Rho activation but did not activate Cdc42. In
      addition, bFGF enhanced fibroblast migration in wound healing assay. The present
      study implicates PI3K, Rac, Rho, and Rho kinase as being involved in bFGF
      stimulated collagen matrix contraction. The elucidation of bFGF-triggered signal
      transduction may be an important clue to understand the roles of bFGF in wound
      healing.

PMID- 17497702
TI  - Generation of transgenic tendon reporters, ScxGFP and ScxAP, using regulatory
      elements of the scleraxis gene.
AB  - Defects in tendon patterning and differentiation are seldom assessed in mouse
      mutants due to the difficulty in visualizing connective tissue structures. To
      facilitate tendon analysis, we have generated mouse lines harboring two different
      transgene reporters, alkaline phosphatase (AP) and green fluorescent protein
      (GFP), each expressed using regulatory elements derived from the endogenous
      Scleraxis (Scx) locus. Scx encodes a transcription factor expressed in all
      developing tendons and ligaments as well as in their progenitors. Both the ScxGFP
      and ScxAP transgenes are expressed in patterns recapitulating almost entirely the
      endogenous developmental expression of Scx including very robust expression in
      the tendons and ligaments. These reporter lines will facilitate isolation of
      tendon cells and phenotypic analysis of these tissues in a variety of genetic
      backgrounds.

PMID- 17497701
TI  - Lovastatin protects mesenchymal stem cells against hypoxia- and serum deprivation
      induced apoptosis by activation of PI3K/Akt and ERK1/2.
AB  - Cell therapy with bone marrow-derived mesenchymal stem cells (MSCs) has been
      shown to have great promises in cardiac repair after myocardial infarction.
      However, poor viability of transplanted MSCs in the infracted heart has limited
      the therapeutic efficacy. Our previous studies have shown in vitro that rat MSCs
      undergo caspase-dependent apoptosis in response to hypoxia and serum deprivation
      (Hypoxia/SD). Recent findings have implicated statins, an established class of
      cholesterol-lowering drugs, enhance the survival of cells under various
      conditions. In this study, we investigated the effect of lovastatin on rat MSCs
      apoptosis induced by Hypoxia/SD, focusing in particular on regulation of
      mitochondrial apoptotic pathway and the survival signaling pathways. We
      demonstrated that lovastatin (0.01-1 microM) remarkably prevented MSCs from
      Hypoxia/SD-induced apoptosis through inhibition of the mitochondrial apoptotic
      pathway, leading to attenuation of caspase-3 activation. The loss of
      mitochondrial membrane potential and cytochrome-c release from mitochondria to
      cytosol were significantly inhibited by lovastatin. Furthermore, the
      antiapoptotic effect of lovastatin on mitochondrial apoptotic pathway was
      effectively abrogated by both PI3K inhibitor, LY294002 and ERK1/2 inhibitor,
      U0126. The phosphorylations of Akt/GSK3 beta and ERK1/2 stimulated by lovastatin
      were detected. The activation of ERK1/2 was inhibited by a PI3K inhibitor,
      LY294002, but U0126, a ERK1/2 inhibitor did not inhibit phosphorylation of Akt
      and GSK3 beta. These data demonstrate that lovastatin protects MSCs from
      Hypoxia/SD-induced apoptosis via PI3K/Akt and MEK/ERK1/2 pathways, suggesting
      that it may prove a useful therapeutic adjunct for transplanting MSCs into
      damaged heart after myocardial infarction.

PMID- 17497703
TI  - Modulation of the amplitude of NAD(P)H fluorescence transients after synaptic
      stimulation.
AB  - In brain slices, excitatory synaptic stimulation results typically in transient
      initial decreases in NAD(P)H fluorescence, followed by longer-lasting NAD(P)H
      increases that overshoot pre-stimulus NAD(P)H levels before returning slowly to
      baseline. We concluded recently that mitochondrial metabolism (rather than NADH
      generation by glycolysis) was responsible for the "overshoot" phase of responses
      evoked in murine hippocampal slices. The present study examined factors that may
      influence the amplitude of the overshoot phase, without necessarily directly
      influencing mitochondrial or glycolytic metabolism. The amplitudes of overshoots
      were influenced strongly by changes in pre-stimulus NAD(P)H fluorescence levels
      produced by a prior electrical stimulus. In contrast, these changes in pre
      stimulus redox state had little effect on the amplitude of evoked initial NAD(P)H
      decreases. Resting NAD(P)H fluorescence levels differed significantly across sub
      regions of each slice, however, this is not due to differences in resting redox
      state, and the relative amplitude of NAD(P)H overshoots were not different in
      different slice regions. Exposure to an A1 receptor agonist (CPA) reduced the
      amplitude of postsynaptic potentials, and preferentially reduced the amplitude of
      NAD(P)H overshoots, before initial oxidizing components of biphasic transients
      were reduced significantly. These results suggest that amplitudes of NAD(P)H
      overshoots may not be good quantitative measures of the intensity of a discrete
      stimulus, under some conditions where the stimulus is small relative to recent
      activity in the slice. Comparison of flavoprotein autofluorescence with NAD(P)H
      levels seems useful when making quantitative comparisons of responses from
      different regions of slices, where optical properties and ongoing activity may be
      substantially different.

PMID- 17497704
TI  - Patterns of menstrual disturbance in eating disorders.
AB  - OBJECTIVE: To describe menstrual disturbance in eating disorders (ED). METHOD: We
      describe menstrual history in 1,705 women and compare eating, weight, and
      psychopathological traits across menstrual groups. RESULTS: Menstrual dysfunction
      occurred across all eating disorder subtypes. Individuals with normal menstrual
      history and primary amenorrhea reported the highest and lowest lifetime body mass
      index (BMI), respectively. Normal menstruation and oligomenorrhea groups reported
      greater binge eating, vomiting, and appetite suppressant use. Amenorrhea was
      associated with lower caloric intake and higher exercise. Harm avoidance, novelty
      seeking, perfectionism, and obsessionality discriminated among menstrual status
      groups. No differences in comorbid Axis I and II disorders were observed.
      CONCLUSION: Menstrual dysfunction is not limited to any eating disorder subtype.
      BMI, caloric intake, and exercise were strongly associated with menstrual
      function. Menstrual status is not associated with comorbidity. Menstrual
      irregularity is an associated feature of all ED rather than being restricted to
      AN only.

PMID- 17497705
TI  - Functional impairment associated with bulimic behaviors in a community sample of
      men and women.
AB  - OBJECTIVE: To examine functional impairment associated with bulimic behaviors in
      a community sample of men and women. METHOD: Binge eating, purging, fasting,
      extreme weight and shape concerns, and "days-out-of-role" were assessed in a
      community sample of men (n = 1,290) and women (n = 1,757) aged 15-94 years.
      RESULTS: Participants who reported regular eating disorder behaviors had higher
      levels of functional impairment than those who did not. This was the case for
      both men and women and for each of the behaviors assessed, although differences
      between purgers and nonpurgers were not statistically significant. Also in both
      men and women, participants who reported eating disorder behaviors and weight or
      shape concerns had higher levels of impairment than those who reported these
      behaviors in the absence of weight or shape concerns. In multivariate analysis,
      binge eating, fasting and weight or shape concerns all contributed to the
      likelihood of impairment in men, whereas only the presence of weight or shape
      concerns was significantly associated with impairment in women. CONCLUSION:
      Whereas bulimic behaviors are associated with elevated levels of functional
      impairment in both men and women, weight or shape concerns may be more central to
      the experience of this impairment in women.

PMID- 17497706
TI  - Weight overestimation as an indicator of disordered eating behaviors among young
      women in the United States.
AB  - OBJECTIVE: This paper examines the association between weight overestimation and
      symptoms of disordered eating behaviors using a nationally representative sample
      of young women. METHOD: We use data from Wave III of the National Longitudinal
      Study of Adolescent Health to compare self-reported weight (in pounds) to measure
      weight obtained by interviewers using a scale. Focusing on normal weight women
      between the ages of 18 and 24 (n = 2,805) we compare the discrepancy in self
      reported and measured weight among women with and without any disordered eating
      behaviors. RESULTS: Women who over report their weight by at least five percent
      are significantly more likely than those who either under report or accurately
      report their weights to exhibit disordered eating behaviors. These results
      persist despite controlling for distorted body image. CONCLUSION: Our findings
      support both motivational and perceptual bias explanations for overestimating
      weight among those who exhibit disordered eating behaviors. We argue that weight
      over-estimation, together with other important information regarding women's
      nutrition, exercise, mental health, and health-related behaviors, should be
      treated as a potential indicator for the diagnosis of an eating disorder among
      young normal weight women.

PMID- 17497707
TI  - Eating disturbances in a school population of preteen girls: assessment and
      screening.
AB  - OBJECTIVE: To assess the utility of the Children's Eating Attitudes Test (cEAT)
      questionnaire in screening for interview-ascertained eating disturbances. METHOD:
      A total of 409 girls, 9-13 years of age, completed a cEDE interview and cEAT
      questionnaire. RESULTS: 14.7% of girls reported eating disturbances in the past
      month on the cEDE. Mean cEDE score was 0.3 +/- 0.6 and mean cEAT score was 5.9 +/
      5.9. The cEAT demonstrated low sensitivity but high specificity at a cutoff
      score of 20, and poor positive predictive value when lower cutoff scores were
      used. CONCLUSION: Eating disturbances were common but mild in this preteen group.
      The cEAT was not an efficient screening tool for interview-ascertained mild
      eating disturbances in preteen girls.

PMID- 17497708
TI  - Health service utilization for eating disorders: findings from a community-based
      study.
AB  - BACKGROUND: Prior use of health services was examined in a community sample of
      women with bulimic-type eating disorders. METHOD: Participants (n = 159)
      completed a structured interview for the assessment of eating disorder
      psychopathology as well as questions concerning treatment-seeking and type of
      treatment received. RESULTS: Whereas a minority (40.3%) of participants had
      received treatment for an eating problem, most had received treatment for a
      general mental health problem (74.2%) and/or weight loss (72.8%), and all had
      used one or more self-help treatments. Where treatment was received for an eating
      or general mental health problem, this was from a primary care practitioner in
      the vast majority of cases. Only half of those participants who reported marked
      impairment associated with an eating problem had ever received treatment for such
      a problem and less than one in five had received such treatment from a mental
      health professional. CONCLUSION: Women with bulimic-type eating disorders rarely
      receive treatment for an eating problem, but frequently receive treatment for a
      general mental health problem and/or for weight loss. The findings underscore the
      importance of programs designed to improve the detection and management of eating
      disorders in primary care.

PMID- 17497709
TI  - Relative reinforcing value of exercise in inpatients with anorexia nervosa: model
      development and pilot data.
AB  - OBJECTIVE: This study sought to quantify, among patients hospitalized for the
      treatment of anorexia nervosa (AN), the reinforcing value of exercise, defined as
      the amount of work a patient would expend for the opportunity to exercise.
      METHOD: Sixteen inpatients with AN performed a computerized progressive ratio
      (PR) task for the opportunity to exercise for either 15 or 30 min, or a monetary
      voucher. Exercise "breakpoint" was calculated and compared with clinical
      measures. RESULTS: Patients performed an average of 1134.4 (+/-751.2) button
      presses for exercise. Exercise breakpoint was significantly correlated with the
      Beck Depression Inventory (BDI; r = .728, p = .001), and there was a trend toward
      a correlation with the Commitment to Exercise Scale (CES; Davis, 1993; r = .490,
      p = .054). CONCLUSION: Results support the feasibility and potential utility of
      this novel application of the PR task to quantify the reinforcing value of
      exercise in AN. The association between exercise and depression is consistent
      with some prior studies in AN. The trend toward an association with CES scores
      suggests that breakpoint captures an aspect of the motivation for exercise in
      this population.

PMID- 17497710
TI  - Assessment of binge eating in overweight youth using a questionnaire version of
      the Child Eating Disorder Examination with Instructions.
AB  - OBJECTIVE: Existing self-report methods for assessing eating disorder (ED)
      symptoms in youth do not adequately measure binge eating and lack sufficient
      psychometric support. The Youth Eating Disorder Examination-Questionnaire (YEDE
      Q), a self-report version of the Child Eating Disorder Examination (ChEDE), was
      designed to assess the spectrum of ED psychopathology in youth. METHOD: The YEDE
      Q was compared to the ChEDE and the Questionnaire for Eating and Weight Patterns
      Adolescent version (QEWP-A) in a sample of 35 overweight adolescents aged 12-17.
      RESULTS: The YEDE-Q showed significant agreement (ps < .001) with the ChEDE on
      all four subscale scores, the global score, and measurement of objective bulimic
      episodes. The YEDE-Q and the QEWP-A showed significant agreement (ps < .001) on
      the measurement of shape and weight concerns. CONCLUSION: The YEDE-Q appears
      promising in the assessment of eating-related pathology in overweight
      adolescents, but remains in need of validation in children and ED populations.

PMID- 17497711
TI  - The use of guidelines for dissemination of "best practice" in primary care of
      patients with eating disorders.
AB  - OBJECTIVE: A number of sets of clinical guidelines have been developed for the
      treatment of eating-disordered patients. This study aimed to measure adherence to
      such guidance among family physicians working in primary care settings. METHOD:
      In the wake of the publication of national guidelines for "best practice," family
      physicians in a large but diverse geographical region of the UK (population of
      6.4 million) were approached and asked to complete a two-stage survey. RESULTS:
      Only 4% of these clinicians report using published guidelines or protocols, and
      none used the national guidelines that were available. Nor were these clinicians
      using the spirit of the guidelines, as there was little correspondence between
      recommended and actual treatment behavior. CONCLUSION: These findings suggest
      that specialist eating disorders services should not rely on guidelines to ensure
      the dissemination of best practice for these patients in primary care.
      Alternative means of dissemination are needed, and suggestions are made.

PMID- 17497712
TI  - Early fetal death associated with compound heterozygosity for Noonan syndrome
      causative PTPN11 mutations.

PMID- 17497713
TI  - Familial unilateral deafness and delayed endolymphatic hydrops.
AB  - Delayed endolymphatic hydrops (DEH) is a unique disorder characterized by
      fluctuating otologic symptoms in the setting of preexisting unilateral deafness.
      The symptoms include aural fullness, fluctuating hearing, and/or episodes of
      vertigo similar to those observed in Meniere disease and may occur ipsilateral or
      contralateral to the previously deafened ear. In most reported cases, the
      unilateral deafness has been a profound sensorineural hearing loss with a sudden
      onset that has been variously attributed to bacterial or viral labyrinthitis,
      acoustic or cranial trauma, otosclerosis, and congenital CMV infection. Familial
      occurrence of the syndrome has not previously been reported in the literature. In
      this report, we describe two possible familial instances of delayed DEH. These
      patients raise the possibility that genetic factors may sometimes be the cause of
      this unusual syndrome.

PMID- 17497714
TI  - Behavioral phenotype of sex chromosome aneuploidies: 48,XXYY, 48,XXXY, and
      49,XXXXY.
AB  - Sex chromosomal aneuploidy is the most common disorder of sex chromosomes in
      humans, with an incidence of 1 in 400 newborns. The addition of more than one
      extra X and/or Y chromosome to a normal male karyotype is less frequent and has
      its own distinctive physical and behavioral profile. This study examines the
      behavioral similarities and differences in individuals with 48,XXYY compared to
      48,XXXY and 49,XXXXY. The participants include 11 males with 48,XXYY and 13 males
      with 48,XXXY and 49,XXXXY. Using the Vineland Adaptive Behavior, the Achenbach
      Child Behavior Checklist, and the Reiss Personality Profiles, parents are asked
      to characterize the behavior and personality of their boys with sex chromosome
      tetrasomy and pentasomy. Males with 48,XXYY have higher overall adaptive scales
      in daily living skills, socialization, and communication compared to males with
      48,XXXY and 49,XXXXY. Both groups are at risk for maladaptive behavior, although
      48,XXYY males are at a higher risk for internalizing and externalizing symptoms.
      48,XXXY and 49,XXXXY function at a lower cognitive level and their behavior is
      often immature for their chronological age. Both groups display interests in
      helping others, but have a low tolerance for being rejected or teased. Specific
      recommendations and interventional strategies are provided for individuals with
      48,XXYY, 48,XXXY, and 49,XXXXY.

PMID- 17497716
TI  - First reported case of intrachromosomal cryptic inv dup del Xp in a boy with
      developmental retardation.
AB  - We report here on a 6-year-old boy referred to the laboratory for karyotyping and
      SHOX microdeletion testing. The most significant clinical findings in this boy
      were small stature, Madelung deformity, facial dysmorphism, mild mental
      retardation and behavioral problems. R-, G- and RTBG-banding chromosome analysis
      showed a normal male karyotype. Fine molecular characterization, by FISH, of
      terminal Xp microdeletion revealed an associated partial duplication. Further
      refinement of the molecular analysis indicated an inverted duplication of the
      Xp22.31-Xp22.32 (13.7 Mb) region including the STS, VCX-A and KAL1 genes,
      associated with a terminal Xp deletion Xp22.33-Xpter (3.6 Mb) encompassing the
      SHOX and ARSE genes. Such rearrangements have been characterized for other
      chromosomal pairs, but this is the first reported male patient involving the
      short arm of the X chromosome. Molecular analysis of the maternal and patient's
      microsatellite markers showed interchromatid mispairing leading to non-allelic
      homologous recombination to be the most likely mechanism underlying this
      rearrangement. This case highlights the importance of clinically driven FISH
      investigations in order to uncover cryptic micro-rearrangements.

PMID- 17497717
TI  - Bipolar affective disorder associated with 11q24.2 disruption--a second report.
AB  - A recent report identified bipolar affective disorder in a patient with a de novo
      deletion 11q24.2. We record a further instance involving this cytogenetic region
      and bipolar affective disorder in a patient with a balanced translocation.

PMID- 17497718
TI  - Esophageal atresia, hypoplasia of zygomatic complex, microcephaly, cup-shaped
      ears, congenital heart defect, and mental retardation--new MCA/MR syndrome in two
      affected sibs and a mildly affected mother?
AB  - The previously undescribed combination of esophageal atresia, hypoplasia of the
      zygomatic complex, microcephaly, cup-shaped ears, congenital heart defect, and
      mental retardation was diagnosed in two siblings of different sexes, with the
      brother being more severely affected. The mother presented with zygomatic arch
      hypoplasia of the right side only. We discuss major differential diagnoses:
      Goldenhar, Feingold, CHARGE, and Treacher Collins syndromes show a few
      overlapping clinical features, but these diagnoses are unlikely as the clinical
      findings are unusual for Goldenhar syndrome and mutational screening of the MYCN,
      the CHD7, and the TCOF1 genes did not reveal any abnormalities. Autosomal
      recessive oto-facial syndrome, hypomandibular faciocranial dysostosis, and Ozkan
      syndromes were clinically excluded. A microdeletion 22q11.2 was excluded by FISH
      analysis, a microdeletion 2p23-p24 by microsatellite analyses, a subtelomeric
      chromosomal aberration by MLPA, and a small genomic deletion/duplication by CGH
      array. As X-inactivation studies did not show skewed X-inactivation in the
      mother, we consider X-chromosomal recessive inheritance of this condition less
      likely. We discuss autosomal dominant inheritance with variable expressivity or
      mosaicism in the mother as the likely genetic mechanism in this new multiple
      congenital anomaly/mental retardation (MCA/MR) syndrome.

PMID- 17497719
TI  - Discordant intrauterine environment may explain discordance in monozygotic twins.

PMID- 17497720
TI  - Hepatic vascular malformation in a patient with Simpson-Golabi-Behmel syndrome.

PMID- 17497721
TI  - Orbicularis oris muscle defects as an expanded phenotypic feature in nonsyndromic
      cleft lip with or without cleft palate.
AB  - Nonsyndromic cleft lip+/-cleft palate is a complex disease with a wide phenotypic
      spectrum; occult defects of the superior orbicularis oris muscle may represent
      the mildest subclinical form of the lip portion of the phenotype. This study used
      high-resolution ultrasonography to compare the frequency of discontinuities in
      the OO muscle in 525 unaffected relatives of individuals with nonsyndromic cleft
      lip+/-cleft palate versus 257 unaffected controls. OO muscle discontinuities were
      observed in 54 (10.3%) of the non-cleft relatives, compared to 15 (5.8%) of the
      controls-a statistically significant increase (P=0.04). Male relatives had a
      significantly higher rate of discontinuities than male controls (12.0% vs. 3.2%;
      P=0.01); female relatives also had a higher rate of discontinuities than female
      controls, but the increase was not statistically significant (8.9% vs. 7.4%;
      P=0.56). These data confirm the hypothesis that subepithelial OO muscle defects
      are a mild manifestation of the cleft lip phenotype. Identification of
      subepithelial OO muscle defects may be important in a clinical setting, as a
      means of providing more accurate recurrence risk estimates to relatives in cleft
      families. Furthermore, the expansion of the cleft lip+/-cleft palate phenotypic
      spectrum should improve the power of genetic studies.

PMID- 17497722
TI  - A triploid fetus further expands etiological heterogeneity in holoprosencephaly
      diencephalic hamartoblastoma.

PMID- 17497723
TI  - A new case of spondyloenchondrodysplasia with immune dysregulation confirms the
      pleiotropic nature of the disorder: comment on "A syndrome of immunodeficiency,
      autoimmunity, and spondylometaphyseal dysplasia" by M.L. Kulkarni, K. Baskar, and
      P.M. Kulkarni [2006].

PMID- 17497724
TI  - The National Niemann-Pick C1 disease database: report of clinical features and
      health problems.
AB  - Niemann-Pick type C1 (NPC1) disease is an autosomal recessive disorder
      characterized clinically by neonatal jaundice, hepatosplenomegaly, vertical gaze
      palsy, ataxia, dystonia, and progressive neurodegeneration. The present study
      provides basic clinical and health information from the National Niemann-Pick C1
      disease database that was obtained using a clinical questionnaire of 83 questions
      mailed to families affected by NPC1 disease living in the United States. The
      study was conducted over a 1-year period, during which time parents/caregivers
      and physicians completed the clinical questionnaire. Sixty-four percent (87/136)
      of the questionnaires were returned, with 53% and 47% representing male and
      female NPC1 patients, respectively. The average age of diagnosis for NPC1 disease
      was 10.4 years, with one-half of patients being diagnosed before the age of 6.9
      years. The average age of death for NPC1 disease was 16.2 years, with one-half of
      patients dying before the age of 12.5 years. A common clinical symptom reported
      at birth was neonatal jaundice (52%), followed by enlargement of the spleen (36%)
      and liver (31%); ascites (19%) and neonatal hypotonia (6%) were much less
      frequent. With respect to developmental difficulties, the most common findings
      included clumsiness (87%), learning difficulties (87%), ataxia (83%), dysphagia
      (80%), and vertical gaze palsy (81%). Together, these findings confirm and extend
      previous reports investigating the clinical features associated with NPC1
      disease.

PMID- 17497725
TI  - Fortuitous detection of a submicroscopic deletion at 1q25 in a girl with Cornelia
      de Lange syndrome carrying t(5;13)(p13.1;q12.1) by array-based comparative
      genomic hybridization.
AB  - We report on a 2-year-old Japanese girl with Cornelia-de Lange syndrome (CdLS)
      who had mental and growth retardation, together with characteristic facial
      anomalies and mild extremity malformations. She had a balanced chromosomal
      translocation, 46,XX,t(5;13)(p13.1;q12.1) de novo. Surprisingly, this was the
      same translocation that had provided a clue to the identification of a major
      causative gene for CdLS, NIPBL [Krantz et al., 2004; Tonkin et al., 2004]. Using
      fluorescence in situ hybridization (FISH), the breakpoint was confirmed to lie
      within NIPBL at 5p13.1. Furthermore, array-based comparative genomic
      hybridization (array-CGH) demonstrated a cryptic 1-Mb deletion harboring six
      known genes at 1q25-q31.1. A FISH analysis of her parents confirmed that the
      deletion was de novo. Although patients with interstitial deletions at 1q are
      rare, some of their features were similar to those observed in our patient,
      indicating that her clinical manifestations are likely to be affected by not only
      the disruption of NIPBL but also the concomitant microdeletion at 1q25-q31.1. The
      present case suggests that array-CGH can uncover cryptic genomic aberrations
      affecting atypical phenotypes even in well-known congenital disorders.

PMID- 17497726
TI  - Effect of propylene glycol on ibuprofen absorption into human skin in vivo.
AB  - The objective was to assess the impact of propylene glycol (PG), a common
      cosolvent in topical formulations, on the penetration of ibuprofen into human
      skin in vivo. Drug uptake into the stratum corneum (SC), following application of
      saturated formulations containing from 0 to 100% v/v PG, was assessed by tape
      stripping. Dermatopharmacokinetic parameters, characterizing drug amount in and
      diffusivity through the SC, were derived. The solubility behavior of ibuprofen in
      PG-water mixtures was carefully evaluated, as were a number of other physical
      properties. Ibuprofen delivery depended on the level of PG in the vehicle,
      despite all formulations containing the drug at equal thermodynamic activity. PG
      appeared to alter the solubility of ibuprofen in the SC (presumably via its own
      uptake into the membrane), the effect becoming more important as the volume
      fraction of cosolvent in the formulation increased. In summary, tape-stripping
      experiments, with careful interpretation, can reveal details of a drug's
      bioavailability in the skin following topical application and may be used to
      probe the mechanism(s) by which certain excipients influence local drug delivery.

PMID- 17497727
TI  - Influence of operating temperature and pressure on the polymorphic transition of
      salmeterol xinafoate in supercritical fluids.
AB  - Precipitation of pure polymorphic forms (I and II) of salmeterol xinafoate (SX)
      in supercritical fluids was investigated as a function of operating pressure and
      temperature. It has been shown that the formation of each polymorph is governed
      by both thermodynamic shift and kinetic effects, which are closely associated
      with the extent of miscibility between the supercritical CO(2) and methanol
      cosolvent. In addition, the surface energetics of SX exhibit a sharp
      discontinuity at the transition point in concordance with the particular
      polymorphic form generated, being essentially independent of the temperature or
      pressure below and above this point. The conditions of complete miscibility of
      the two solvent phases involved are critical for the formation of SX Form II.

PMID- 17497728
TI  - Selective oxidation of Zn2+ -insulin catalyzed by Cu2+.
AB  - The purpose of this study is to quantitate the sensitivity of Zn2+ -insulin to
      oxidation catalyzed by various redox active transition metals, Cu2+, Fe2+, Mn2+,
      Ni2+, Co2+, Cr3+. Human recombinant insulin (INS) was subjected to oxidation
      under various conditions in the presence and absence of Zn2+ and ascorbate. The
      extent of oxidation was monitored by RP-HPLC. Only Cu2+, but none of the other
      metals or combination thereof, for example, Ni2+/Co2+, Co2+/Cr3+, and Ni2+/Cr3+,
      catalyzed INS oxidation, for example, to an extent of 45% when 20 microM INS/8.8
      microM Zn2+ were exposed to 8 microM Cu2+ and 50 microM ascorbate for 90 min. The
      Cu2+ -catalyzed oxidation mainly targeted the B chain of INS, where the two
      histidine residues are located.

PMID- 17497729
TI  - Tablets with material gradients fabricated by three-dimensional printing.
AB  - Complex tablets with zero-order drug release characteristics were fabricated
      using three-dimensional printing processes. The matrix tablets exhibited material
      gradients in radial direction and had drug-free release-barrier layers on both
      bases. The content of model drug acetaminophen incorporated in the tablets
      through premixing reached up to 68% of the tablets' weight. Tablets with
      ethylcellulose gradients showed acceptable mechanical and pharmacotechnical
      properties, as indicated by crushing strength, friability, and content uniformity
      tests. The structure and the gradients of ethylcellulose in the tablets were
      envisaged through environmental scanning electron microscopy and fluorescence
      tracing technique. Erosion and dissolution studies in vitro indicated that drug
      was released via a two-dimensional surface erosion mechanism, and 98% of the drug
      could be released linearly in 12 h. Tablets with other release-retardation
      material gradients such as sodium lauryl sulfate, stearic acid, and Eudragit RS
      100 showed similar release-retardation effects by different release-retardation
      mechanisms. Through the printing of release-retardation materials, 3DP processes
      could easily prepare tablets with high dosage and special design features for
      furnishing the desired drug release characteristics.

PMID- 17497730
TI  - Acute hydrodynamic forces and apoptosis: a complex question.
AB  - A second generation flow contraction device was developed and modeled which
      allows cells to be subjected to well-defined hydrodynamic forces. Studies were
      conducted with this system on wild-type Chinese Hamster Ovary cells (CHO-K1) and
      a strain of CHO cells which expresses the human Bcl-2 triangle gene (CHO-bcl-2).
      In this study, the following questions were asked: (1) Does an acute hydrodynamic
      force induce apoptosis in wild-type CHO and CHO-bcl-2 cells? (2) Does the type of
      culture media make a difference with respect to the induction of apoptosis or
      necrosis? and (3) Does culture history affect induction of apoptosis or necrosis?
      The results obtained with this new flow contraction device and corresponding
      computer simulations are consistent with previously published studies with
      respect to the level of energy dissipation rate (EDR) required to create
      significant cell lysis. Second, while detectable relative to the control in the T
      flask experiments, only a small fraction of the cells become apoptotic when
      exposed to a sub-lysis level of EDR (<10(8) W x m(-3)). Third, cells cultured in
      suspension with serum free media do not exhibit any higher or lower sensitivity
      (with respect to apoptosis) to various levels of EDR when compared to control
      cultures grown in T-flask and serum containing media; on the other hand, necrosis
      is significantly increased in experiments performed on suspended cells without
      serum. Fourth, the addition of the Bcl-2 gene product might slightly reduce the
      occurrence of apoptosis in T-flask culture; however, the baseline response is so
      low that the difference is insignificant.

PMID- 17497732
TI  - Large-scale biodiesel production from microalga Chlorella protothecoides through
      heterotrophic cultivation in bioreactors.
AB  - An integrated approach of biodiesel production from heterotrophic Chlorella
      protothecoides focused on scaling up fermentation in bioreactors was reported in
      this study. Through substrate feeding and fermentation process controls, the cell
      density of C. protothecoides achieved 15.5 g L(-1) in 5 L, 12.8 g L(-1) in 750 L,
      and 14.2 g L(-1) in 11,000 L bioreactors, respectively. Resulted from
      heterotrophic metabolism, the lipid content reached 46.1%, 48.7%, and 44.3% of
      cell dry weight in samples from 5 L, 750 L, and 11,000 L bioreactors,
      respectively. Transesterification of the microalgal oil was catalyzed by
      immobilized lipase from Candidia sp. 99-125. With 75% lipase (12,000 U g(-1),
      based on lipid quantity) and 3:1 molar ratio of methanol to oil batch-fed at
      three times, 98.15% of the oil was converted to monoalkyl esters of fatty acids
      in 12 h. The expanded biodiesel production rates were 7.02 g L(-1), 6.12 g L(-1),
      and 6.24 g L(-1) in 5 L, 750 L, and 11,000 L bioreactors, respectively. The
      properties of biodiesel from Chlorella were comparable to conventional diesel
      fuel and comply with the US Standard for Biodiesel (ASTM 6751). These results
      suggest that it is feasible to expand heterotrophic Chlorella fermentation for
      biodiesel production at the industry level.

PMID- 17497731
TI  - A stirred microchamber for oxygen consumption rate measurements with pancreatic
      islets.
AB  - Improvements in pancreatic islet transplantation for treatment of diabetes are
      hindered by the absence of meaningful islet quality assessment methods. Oxygen
      consumption rate (OCR) has previously been used to assess the quality of organs
      and primary tissue for transplantation. In this study, we describe and
      characterize a stirred microchamber for measuring OCR with small quantities of
      islets. The device has a titanium body with a chamber volume of about 200 microL
      and is magnetically stirred and water jacketed for temperature control. Oxygen
      partial pressure (pO(2)) is measured by fluorescence quenching with a fiber optic
      probe, and OCR is determined from the linear decrease of pO(2) with time. We
      demonstrate that measurements can be made rapidly and with high precision.
      Measurements with betaTC3 cells and islets show that OCR is directly proportional
      to the number of viable cells in mixtures of live and dead cells and correlate
      linearly with membrane integrity measurements made with cells that have been
      cultured for 24 h under various stressful conditions.

PMID- 17497733
TI  - Relative in vitro efficacy of the phosphate binders lanthanum carbonate and
      sevelamer hydrochloride.
AB  - The high tablet burden and poor compliance associated with phosphate-binding
      drugs has led to a search for more potent agents. In vitro-binding studies were
      performed on the recently introduced binder, lanthanum carbonate (LC; Fosrenol),
      to compare its phosphate-binding affinity with sevelamer hydrochloride (SH;
      Renagel). Langmuir equilibrium binding affinities (K(1)) for LC and SH were
      established using different phosphorus (5-100 mM) and binder (134-670 mg per 50
      mL) concentrations at pH 3-7, with or without salts of bile acids present (30
      mM). At all pH levels, LC had a higher binding affinity for phosphate than SH.
      For LC, K(1) was 6.1 +/- 1.0 mM(-1) and was independent of pH. For SH, K(1) was
      pH dependent, being 1.5 +/- 0.8 mM(-1) at pH 5-7 and 0.025 +/- 0.002 mM(-1) at pH
      3, that is, >200 times lower than for LC. In the presence of 30 mM bile salts, SH
      lost 50% of its phosphate, whereas no displacement of phosphate occurred for LC.
      These findings indicate that LC binds phosphate more effectively than SH across
      the pH range encountered in the gastrointestinal tract, and has a lower
      propensity for bound phosphate to be displaced by competing anions in the
      intestine.

PMID- 17497734
TI  - New method to determine the mass transfer resistance of sterile closures for
      shaken bioreactors.
AB  - In this paper a novel and easily applied method to measure the mass transfer
      resistance of the sterile closures (e.g. cotton plug) of shaken bioreactors is
      introduced. This method requires no investment in special equipment (e.g. an
      oxygen sensor) and can be performed with the materials usually available in
      typical laboratories. The method is based on the model of Henzler et al. (1986),
      which mechanistically describes mass transfer through the sterile closure of a
      shaken bioreactor based on diffusion coupled with Stefan convection. The
      concentration dependency of the multi-component diffusion coefficients is taken
      into account. The water loss from two equivalent shaken bioreactors equipped with
      sterile closures during several days of shaking is measured. One flask contains
      distilled water, the other a saturated salt solution. From the water evaporation
      rate in each of the two flasks, the new model presented calculates the relative
      humidity in the environment, the average diffusion coefficient of oxygen in the
      sterile closure (D(O2)), and the diffusion coefficient of carbon dioxide (D(CO2))
      . The diffusion coefficient of carbon dioxide (D(CO2)) only depends on the
      density and material properties of the sterile closure and not on the gas
      concentrations and is, therefore, an ideal parameter for the characterization of
      the mass transfer resistance. This new method is validated experimentally by
      comparing the diffusion coefficient of oxygen (D(O2)) to a measurement by the
      classic dynamic method; and by comparing the calculated relative humidity in the
      environment to a humidity sensor measurement.

PMID- 17497735
TI  - Tricalcium phosphate delayed release formulation for oral delivery of insulin: a
      proof-of-concept study.
AB  - Several attempts have been made for delivering insulin orally utilizing several
      polymers with varying degrees of effectiveness. A major obstacle associated with
      polymeric delivery system for protein or polypeptide drugs is the poor retention
      of the structure and its biological activity of encapsulated proteins
      particularly for the unstable insulin. Calcium phosphate ceramic is considered
      highly compatible to protein or peptide drugs, particularly insulin. Therefore,
      an attempt has been made to load insulin in tricalcium phosphate (TCP)
      microspheres and coat with pH sensitive polymer of methacrylate derivative, and
      to study the stability and conformational variations of loaded insulin, and
      finally the biological activity of the formulation in diabetic rats. TCP
      microspheres were prepared by a standard procedure. Human insulin was loaded in
      to these porous microspheres by diffusion filling and coated with Eudragit S100.
      This was subjected to in vitro release studies in simulated fluids and the
      stability and conformational variations of the released insulin were studied
      using photon correlation spectroscopy and circular dichroism (CD). Biological
      activity of the formulation was studied on induced diabetic rats. Insulin
      released in the intestinal fluid (SIF) maintained the native conformation without
      showing any aggregation. A dose dependent reduction of blood glucose level (BGL)
      was achieved in streptozotocin induced diabetic Wistar rats, demonstrating its
      biological activity. It has been established from this preliminary study that
      insulin loaded in to TCP microspheres is highly compatible with no degradation or
      loss of biological activity of loaded insulin. The TCP microsphere based delayed
      release formulation of insulin has effected a decrease in elevated glucose level
      in induced diabetic rats, establishing its feasibility towards the development of
      a noninvasive delivery device.

PMID- 17497736
TI  - A comparative study of the antigen-specific immune response induced by co
      delivery of CpG ODN and antigen using fusion molecules or biodegradable
      microparticles.
AB  - CpG ODN are toll-like receptor 9 (TLR9) agonists that can enhance antigen
      presentation by antigen presenting cells (APCs) such as dendritic cells (DCs).
      The most potent antigen-specific responses are seen when CpG ODN and the antigen
      are co-localized in the same APC. CpG ODN-antigen fusion molecules and
      biodegradable microparticles entrapping CpG ODN and antigen can ensure both
      components are delivered to the same APC. In this study, we compared the efficacy
      of the CpG-ODN fusion molecules against biodegradable microparticles entrapping
      antigen and CpG ODN. Microparticles were prepared using a double emulsion solvent
      evaporation methodology. CpG ODN-OVA fusion molecules were prepared by mixing
      maleimide-activated protein with thiolated CpG ODN. Both CpG ODN-OVA fusion
      molecules and microparticles co-entrapping CpG ODN and OVA generated stronger
      IgG2a and interferon-gamma (IFN-gamma) responses than delivery of soluble CpG ODN
      and OVA. The microparticles generated stronger IgG2a and IFN-gamma immune
      responses than did CpG ODN-antigen fusion molecules.

PMID- 17497737
TI  - Oiling out or molten hydrate-liquid-liquid phase separation in the system
      vanillin-water.
AB  - Vanillin crystals in a saturated aqueous solution disappear and a second liquid
      phase emerges when the temperature is raised above 51 degrees C. The phenomenon
      has been investigated with crystallization and equilibration experiments, using
      DSC, TGA, XRD and hot-stage microscopy for analysis. The new liquid solidifies on
      cooling, appears to melt at 51 degrees C, and has a composition corresponding to
      a dihydrate. However, no solid hydrate can be detected by XRD, and it is shown
      that the true explanation is that a liquid-liquid phase separation occurs above
      51 degrees C where the vanillin-rich phase has a composition close to a
      dihydrate. To our knowledge, liquid-liquid phase separation has not previously
      been reported for the system vanillin-water, even though thousands of tonnes of
      vanillin are produced globally every year.

PMID- 17497738
TI  - Expression of two recombinant chloramphenicol acetyltransferase variants in
      highly reduced genome Escherichia coli strains.
AB  - Highly reduced E. coli strains, MDS40, MDS41, and MDS42, lacking approximately
      15% of the genome, were grown to high cell densities to test their ability to
      produce a recombinant protein with high yields. These strains lack all
      transposons and insertion sequences, cryptic prophage and many genes of unknown
      function. In addition to improving genetic stability, these deletions may reduce
      the biosynthetic requirements of the cell potentially allowing more efficient
      production of recombinant protein. Basic growth parameters and the ability of the
      strains to produce chloramphenicol acetyltransferase (CAT) under high cell
      density, batch cultivation were assessed. Although growth rate and recombinant
      protein production of the reduced genome strains are comparable to the parental
      MG1655 strain, the reduced genome strains were found to accumulate significant
      amounts of acetate in the medium at the expense of additional biomass. A number
      of hypotheses were examined to explain the accumulation of acetate, including
      oxygen limitation, carbon flux imbalance, and metabolic activity of the
      recombinant protein. Use of a non-catalytic CAT variant identified the
      recombinant protein activity as the source of this phenomenon; implications for
      the metabolic efficiency of the reduced genome strains are discussed.

PMID- 17497739
TI  - Controlled porosity-osmotic pump pellets of a poorly water-soluble drug using
      sulfobutylether-beta-cyclodextrin, (SBE) 7M-beta-CD, as a solubilizing and
      osmotic agent.
AB  - The objective of this work was to demonstrate that the incorporation of
      sulfobutylether-beta-cyclodextrin, (SBE)(7M)-beta-CD, results in the complete and
      sustained release of a sparingly water-soluble drug, prednisolone (PDL) from
      controlled porosity-osmotic pump pellets (CP-OPP). PDL and CD were prepared in
      various formulations (physical mixtures and presumed preformed complex). Several
      factors influencing drug and CD release were explored, and the probable
      mechanisms of drug release were probed and discussed. A significant improvement
      in the release of PDL from the CP-OPPs was observed by the incorporation of CD
      relative to the coated pellet formulation containing lactose in place of the CD.
      The release profiles of PDL depend on the molar ratio of CD to PDL, thickness of
      the microporous membrane, and osmotic pressure difference across the membrane.
      PDL appears to be released as an in situ complex with CD via mainly osmotic
      pumping during at least the initial portion of the release profiles.

PMID- 17497740
TI  - Affinity purification of plasmid DNA directly from crude bacterial cell lysates.
AB  - We have shown previously that a sequence-specific DNA-binding protein based on
      the Lac repressor protein can isolate pre-purified DNA efficiently from simple
      buffer solution but our attempts to purify plasmids directly from crude starting
      materials were disappointing with impractically low DNA yields. We have optimized
      the procedure and present a simple affinity methodology whereby plasmid DNA is
      purified directly by mixing two crude cell lysates, one cell lysate containing
      the plasmid and the other the protein affinity ligand, without the need for
      treatment by RNaseA. After IMAC chromatography, high purity supercoiled DNA is
      recovered in good yields of 100-150 microg plasmid per 200 mL shake flask
      culture. Moreover, the resulting DNA is free from linear or open-circular plasmid
      DNA, genomic DNA, RNA, and protein, to the limits of our detection. Furthermore,
      we show that lyophilized affinity ligand can be stored at room temperature and re
      hydrated for use when required.

PMID- 17497741
TI  - Studies on aerosol delivery of plasmid DNA using a mesh nebulizer.
AB  - Aerosol delivery of plasmid DNA therapeutic solutions is promising for the
      treatment of respiratory diseases. However, it poses challenges, most
      significantly the need to protect the delicate supercoiled (sc) structure of
      plasmid during aerosolization. Nebulizers for liquid aerosolization using meshes
      appear a better method for delivery than conventional jet and ultrasonic
      nebulizers. This paper explores their application to the delivery of plasmid DNA.
      A computational fluid dynamics model of the dynamics of fluid flow through the
      nozzle of the MicroAIR mesh nebulizer indicated high strain rates (>10(5) s(-1))
      near the nozzle exit capable of causing damage to the shear-sensitive plasmid
      DNA. Knowledge of the strain rates predicted using CFD and molecule size
      determined using atomic force microscopy (AFM) enabled estimation of the
      hydrodynamic force and whether damage of shear-sensitive therapeutics was likely.
      Plasmids of size 5.7 and 20 kb were aerosolized in the mesh nebulizer. The sc
      structure of the 5.7-kb plasmid was successfully delivered without damage, while
      aerosolization of the 20-kb plasmid led to disintegration of the pDNA sc
      structure as observed in AFM. Subsequent formulation of the sc 20-kb plasmid with
      PEI resulted in successful aerosol delivery. The maximum hydrodynamic forces
      computed for the aerosolization of structures of the size of 5.7-kb and PEI
      formulated 20-kb plasmids were less than the forces reported to damage the
      structure of double-stranded DNA. A combination of CFD analysis and structure
      analysis may be used to predict successful aerosol delivery in such a mesh
      nebulizer.

PMID- 17497742
TI  - Human endothelial cell growth and phenotypic expression on three dimensional
      poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue
      engineering.
AB  - Bone tissue engineering offers promising alternatives to repair and restore
      tissues. Our laboratory has employed poly(lactide-co-glycolide) PLAGA
      microspheres to develop a three dimensional (3-D) porous bioresorbable scaffold
      with a biomimetic pore structure. Osseous healing and integration with the
      surrounding tissue depends in part on new blood vessel formation within the
      porous structure. Since endothelial cells play a key role in angiogenesis
      (formation of new blood vessels from pre-existing vasculature), the purpose of
      this study was to better understand human endothelial cell attachment, viability,
      growth, and phenotypic expression on sintered PLAGA microsphere scaffold.
      Scanning electron microscopy (SEM) examination showed cells attaching to the
      surface of microspheres and bridging the pores between the microspheres. Cell
      proliferation studies indicated that cell number increased during early stages
      and reached a plateau between days 10 and 14. Immunofluorescent staining for
      actin showed that cells were proliferating three dimensionally through the
      scaffolds while staining for PECAM-1 (platelet endothelial cell adhesion
      molecule) displayed typical localization at cell-cell contacts. Gene expression
      analysis showed that endothelial cells grown on PLAGA scaffolds maintained their
      normal characteristic phenotype. The cell proliferation and phenotypic expression
      were independent of scaffold pore architecture. These results demonstrate that
      PLAGA sintered microsphere scaffolds can support the growth and biological
      functions of human endothelial cells. The insights from this study should aid
      future studies aimed at enhancing angiogenesis in three dimensional tissue
      engineered scaffolds.

PMID- 17497743
TI  - Coupling kinetic expressions and metabolic networks for predicting wine
      fermentations.
AB  - Problematic fermentations are commonplace and cause wine industry producers
      substantial economic losses through wasted tank capacity and low value final
      products. Being able to predict such fermentations would enable enologists to
      take preventive actions. In this study we modeled sugar uptake kinetics and
      coupled them to a previously developed stoichiometric model, which describes the
      anaerobic metabolism of Saccharomyces cerevisiae. The resulting model was used to
      predict normal and slow fermentations under winemaking conditions. The effects of
      fermentation temperature and initial nitrogen concentration were modeled through
      an efficiency factor incorporated into the sugar uptake expressions. The model
      required few initial parameters to successfully reproduce glucose, fructose, and
      ethanol profiles of laboratory and industrial fermentations. Glycerol and biomass
      profiles were successfully predicted in nitrogen rich cultures. The time normal
      or slow wine fermentations needed to complete the process was predicted
      accurately, at different temperatures. Simulations with a model representing a
      genetically modified yeast fermentation, reproduced qualitatively well literature
      results regarding the formation of minor compounds involved in wine complexity
      and aroma. Therefore, the model also proves useful to explore the effects of
      genetic modifications on fermentation profiles.

PMID- 17497744
TI  - Prenatal determination of the fetal RhD blood group by multiplex PCR: a 7-year
      Portuguese experience.
AB  - OBJECTIVES: This is a retrospective study to evaluate the efficacy and accuracy
      of the multiplex polymerase chain reaction (PCR) amplification, for early
      detection of fetuses at risk for hemolytic disease, in the population living in
      Portugal, and to characterize the RhD-negative individuals at serologic and
      molecular level. METHODS: 2030 uncultured amniotic fluid samples and 2012 blood
      samples from the respective RhD-negative pregnant women were studied by multiplex
      PCR of intron 3/intron 4, exon 7 and 3'UTR. Amniocentesis was performed for a
      variety of medical indications. For quality control, serologic RhD blood groups
      were determined in the cord blood, after birth. RESULTS: 1361 fetal amniotic
      samples were RhD-positive (67%), 669 were RhD-negative. The average time for
      diagnosis was 2 days for uncultured amniocytes and the molecular versus serologic
      RhD typing (n = 809) had 99.5% concordance. Among the 2012 serologic RhD-negative
      mothers, 26 had an RhD-positive allele. CONCLUSION: The multiplex PCR
      amplification used in this study was a rapid and accurate method to determine the
      RhD blood type in the population living in Portugal, being a great tool for
      management of pregnancies with fetuses at risk for alloimmune hemolytic disease.
      In this population, 1.3% of the serologic RhD-negative women have an RHD-positive
      allele.

PMID- 17497745
TI  - Prognostic relevance of circulating matrix metalloproteinase-2 in acute myeloid
      leukaemia patients.
AB  - Matrix metalloproteinases (MMPs) were postulated to have important implication in
      progression and invasiveness of many malignant disorders. On the other hand the
      biological role of MMP-2 in acute myeloid leukaemia (AML) is not fully clear.
      Serum samples from 37 adult patients with AML had been taken before chemotherapy
      was administered. In addition 20 out of the 37 patients were analysed again after
      achieving complete remission (CR). Ten samples from healthy volunteers were
      evaluated as the control. Total MMP-2 levels were measured using ELISA Kit
      obtained from R&D system. MMP-2 serum levels were significantly lower in
      pretreatment AML patients than that in the normal controls (p = 0.000) and in CR
      (p = 0.007). No significant correlations were detected between pretreatment sMMP
      2 levels and FAB subtypes, peripheral blood blast cell counts, peripheral blood
      WBCs, bone marrow blast cell counts or blast cell distribution ratio. The
      prognostic value of MMP-2 was evaluated by dividing AML patients into high and
      low MMP-2 groups using the pretreatment median MMP-2 level of the AML group as
      the cut-off. The authors found that patients in the high group survived for a
      significantly shorter time than those patients in the lower MMP-2 group. High
      pretreatment levels of sMMP-2 among AML patients were associated with poor
      survival. Prospective studies are recommended to establish the clinical value of
      longitudinal sMMP-2 measurement.

PMID- 17497746
TI  - Prenatal diagnosis of trisomy 17 mosaicism.

PMID- 17497747
TI  - Prenatal ultrasound diagnosis of vasa praevia and analysis of risk factors.
AB  - OBJECTIVE: To evaluate the role of ultrasound in prenatal diagnosis of vasa
      praevia (VP) and to asses the risk of VP associated with different causal
      factors. MATERIAL AND METHODS: A retrospective study of the incidence of VP in a
      series of 12,063 deliveries between January 2000 and March 2005. We also studied
      the factors that predisposed for VP and the perinatal outcome of pregnancies.
      RESULTS: The prevalence of VP in our centre during this period was 0.07% (9
      cases). All cases were prenatally diagnosed. The mean gestational age at
      diagnosis was 26 weeks. Multivariate analysis revealed the following associated
      factors: IVF pregnancies, bilobate or succenturiate placenta, and second
      trimester placenta praevia, with an odds ratio of 7.75, 22.11 and 22.86,
      respectively. CONCLUSIONS: In our series, the prenatal diagnosis of all cases of
      VP achieved during the second-trimester scan allowed us to avoid any prenatal
      death related to this condition.

PMID- 17497748
TI  - A case of agnathia-otocephaly complex assessed prenatally for ex utero
      intrapartum treatment (EXIT) by three-dimensional ultrasonography.

PMID- 17497749
TI  - Diagnosis of Apert syndrome in the second-trimester using 2D and 3D ultrasound.
AB  - OBJECTIVES: To illustrate how Apert syndrome, a rare autosomal dominant genetic
      syndrome, can be detected in the second-trimester of pregnancy using 2D
      ultrasound, and how 3D ultrasound examination may provide parents with a better
      understanding of the structural defects affecting their baby. METHODS: Fetal
      Medicine Unit database searches to identify Apert syndrome cases. RESULTS: Five
      cases of Apert syndrome were suspected in the second-trimester when sonography
      showed abnormal extremities including syndactyly, and an abnormal skull shape. In
      1 case there was increased nuchal translucency with a normal fetal karyotype in
      the first-trimester. In all cases, a mutation of the FGFR2 gene confirmed the
      diagnosis of Apert syndrome. 3D ultrasound was used to show parents the extent of
      the abnormalities of the skull, face and extremities. Parents were counseled by
      craniofacial surgeons and geneticists. CONCLUSION: Apert syndrome can be
      accurately suspected in the second-trimester by careful ultrasound examination of
      the fetus including the extremities and skull shape. 3D ultrasound can be a
      useful adjunct to 2D examination for parental counseling.

PMID- 17497750
TI  - French midwives' practice of termination of pregnancy for fetal abnormality. At
      what psychological and ethical cost?
AB  - OBJECTIVES: To study the clinical, emotional and moral difficulties that French
      midwives encounter in the labor ward while performing termination of pregnancy
      (TOP) for fetal abnormality. SETTING: Six public maternity hospitals located in
      the Ile de France region, two of which were referral centers for prenatal
      diagnosis (PND) and TOP. METHOD: Questionnaire survey RESULTS: Ninety-two of 115
      midwives responded. Sixty-five percent of the midwives reported that their role
      in the labor ward during TOP was difficult. Aspects contributing substantially to
      the perceived difficulties were the midwives' responsibility to provide
      psychological support to patients and the emotional distress of the midwives
      themselves. Seventy-five percent reported that they were concerned about the
      child being alive in cases of late TOP. Twenty-five percent of the midwives
      reported moral conflicts due to personal, cultural or religious background,
      mainly for particular indications. There was a consensus about the clinical
      management of TOP. Overall, midwives with professional experience, training, and
      those who worked in a referral center reported fewer difficulties. CONCLUSION: It
      is necessary to improve institutional support available within maternity units to
      alleviate the difficulties midwives face in their roles. The need for
      training/updating midwives about psychological and ethical aspects of TOP should
      also be considered.

PMID- 17497751
TI  - An opportunity cost approach to sample size calculation in cost-effectiveness
      analysis.
AB  - The inclusion of economic evaluations as part of clinical trials has led to
      concerns about the adequacy of trial sample size to support such analysis. The
      analytical tool of cost-effectiveness analysis is the incremental cost
      effectiveness ratio (ICER), which is compared with a threshold value (lambda) as
      a method to determine the efficiency of a health-care intervention. Accordingly,
      many of the methods suggested to calculating the sample size requirements for the
      economic component of clinical trials are based on the properties of the ICER.
      However, use of the ICER and a threshold value as a basis for determining
      efficiency has been shown to be inconsistent with the economic concept of
      opportunity cost. As a result, the validity of the ICER-based approaches to
      sample size calculations can be challenged. Alternative methods for determining
      improvements in efficiency have been presented in the literature that does not
      depend upon ICER values. In this paper, we develop an opportunity cost approach
      to calculating sample size for economic evaluations alongside clinical trials,
      and illustrate the approach using a numerical example. We compare the sample size
      requirement of the opportunity cost method with the ICER threshold method. In
      general, either method may yield the larger required sample size. However, the
      opportunity cost approach, although simple to use, has additional data
      requirements. We believe that the additional data requirements represent a small
      price to pay for being able to perform an analysis consistent with both concept
      of opportunity cost and the problem faced by decision makers.

PMID- 17497752
TI  - Activity of cyazofamid against Sclerospora graminicola, a downy mildew disease of
      pearl millet.
AB  - The efficacy of cyazofamid was tested against pearl millet downy mildew disease
      caused by Sclerospora graminicola Schroet. Significant inhibition of sporangial
      sporulation, zoospore release and motility was observed at 0.3 mg mL(-1), and
      this concentration also provided good fungicidal activity under in vitro
      conditions. Under glasshouse conditions, none of the concentrations tested,
      either 0.01-2 mg mL(-1) as seed treatment or 1-10 mg mL(-1) by foliar
      application, was found to be phytotoxic. The effect of cyazofamid was tested by
      seed treatment alone, seed treatment followed by foliar application and foliar
      application alone. Seed treatment with cyazofamid offered only 19.7% disease
      control, but seed treatment followed by a single foliar application to diseased
      plants provided good control over disease, seed treatment with two foliar
      applications was significantly superior and foliar application alone showed a
      high level of activity, with 10 mg mL(-1) giving 97.9% disease control. Lack of
      systemic activity of cyazofamid was evident, root treatment giving disease levels
      on a par with the untreated control. The fungicide exhibited strong curative
      activity, but only moderate translaminar activity, with only marginal (34.8%)
      disease control after treatment of the adaxial leaf surface at 10 mg mL(-1). Loss
      of cyazofamid activity over time was very low, indicating stable residual and
      rainfastness activity. These results indicate that cyazofamid has a high
      potential to be an effective fungicide for the control of downy mildew disease of
      pearl millet.

PMID- 17497753
TI  - Pelvic floor function in elite nulliparous athletes.
AB  - OBJECTIVE: There is preliminary evidence linking long-term participation in high
      impact exercise with poor performance in labor and increased incidence of stress
      urinary incontinence, which may be due to altered pelvic floor function. Recent
      work has shown that HIFIT (high-impact, frequent intense training) athletes have
      an increased cross-sectional area of the levator ani muscle group as visualized
      using magnetic resonance imaging (MRI). The aim of this study was to further
      characterize pelvic floor muscle function and pelvic organ descent in a
      nulliparous athletic population and compare it with non-athletic controls matched
      for age and body mass index, using three-dimensional/four-dimensional (3D/4D)
      pelvic floor ultrasound imaging. METHODS: In this prospective comparative study
      translabial ultrasound imaging was used to assess pelvic floor anatomy and
      function in 46 nulliparous female volunteers (aged 19-39 years), 24 HIFIT and 22
      controls. Two-dimensional (2D) and 3D translabial ultrasonography was performed
      on all subjects, after voiding and in the supine position. Descent of the pelvic
      organs was assessed on maximum Valsalva maneuver, whilst volume datasets were
      acquired at rest, during pelvic floor muscle contraction and during a Valsalva
      maneuver. Participants performed each maneuver at least three times and the most
      effective was used for evaluation. RESULTS: HIFIT athletes showed a higher mean
      diameter of the pubovisceral muscle (0.96 cm vs. 0.70 cm, P < 0.01), greater
      bladder neck descent (22.7 mm vs. 15.1 mm, P = 0.03) and a larger hiatal area on
      Valsalva maneuver (21.53 vs. 14.91 cm(2), P = 0.013) compared with the control
      group. There were no significant differences in hiatal area at rest or on maximal
      voluntary contraction between the two groups. CONCLUSION: HIFIT athletes show
      significant differences in several of the measured parameters for both function
      and anatomy of the pelvic floor. Further research into the impact of this altered
      function on childbirth and continence mechanisms is needed.

PMID- 17497754
TI  - Validated ion pair liquid chromatography/fluorescence detection method for
      assessing the variability of the loratadine metabolism occurring in
      bioequivalence studies.
AB  - Inter- and intra-individual variability of the loratadine (LOR) metabolism in
      Caucasian subjects was assessed during a bioequivalence study for two
      pharmaceutical formulations (solid oral dosage forms) containing 10 mg of the
      active substance. The analytical data were obtained by applying a reliable, low
      cost and sensitive ion pair liquid chromatography/fluorescence (IPLC/FLD) method
      for determination of both loratadine and descarboethoxyloratadine (DCL) in human
      plasma samples. The sample preparation procedure is based on liquid-liquid
      extraction of the target analytes from alkalinized plasma using diethyl-ether.
      The separation of the analytes and 8-chloroazatadine as internal standard (IS)
      was achieved through an isocratic ion pair (IP) elution on a Purospher((R)) STAR
      RP-18 column. The mobile phase containing sodium dodecyl sulfate (SDS) as ion
      pairing agent was pumped at a flow rate of 1 mL/min. Fluorescence detection (FLD)
      was achieved at 280 nm (excitation) and 440 nm (emission) wavelengths. The
      increased sensitivity of the method is also based on a large sample injected
      volume (250 microL). Linear response was found over the 0.5-20 ng/mL
      concentration interval for both target compounds. Low limits of quantification
      (LLOQ) around 0.3 ng/mL were found for LOR and DCL. Method validation is
      presented.

PMID- 17497755
TI  - Plasma tissue factor is a predictor for restenosis after femoropopliteal
      angioplasty.
AB  - BACKGROUND: In vitro studies suggest an association between raised levels of
      tissue factor and restenosis after coronary percutaneous transluminal angioplasty
      (PTA). This prospective, controlled study examined the association between plasma
      tissue factor concentrations and restenosis after femoropopliteal PTA. METHODS:
      Plasma samples from ten healthy controls and 36 patients with unilateral
      claudication undergoing femoropopliteal PTA were collected at baseline and, in
      the patients with claudication, at 24 h and 1, 3 and 6 months after PTA. Clinical
      assessment and arterial duplex imaging were performed before and at the same time
      points after PTA to identify restenosis. Plasma tissue factor was measured using
      a specific enzyme-linked immunosorbent assay. RESULTS: Baseline plasma tissue
      factor concentrations were significantly higher in patients with claudication
      (median 3.4 (interquartile range (i.q.r.) 1.3-7.4) ng/ml) than in controls
      (median 1.2 (i.q.r. 0.5-1.8) ng/ml) (P < 0.050). Baseline tissue factor
      concentrations were significantly higher in the ten patients with claudication
      who developed restenosis after PTA (median 7.0 (i.q.r. 3.4-183.5) ng/ml) than in
      those who did not (median 1.7 (i.q.r. 1.3-7.2) ng/ml) (P < 0.050). In addition,
      plasma tissue factor levels increased significantly over time in the patients who
      developed restenosis after PTA. CONCLUSION: High baseline and progressive
      increases in the plasma tissue factor concentration were useful predictors of
      restenosis after femoropopliteal angioplasty.

PMID- 17497756
TI  - Functional results after extended myotomy for diffuse oesophageal spasm.
AB  - BACKGROUND: The role of surgery in the management of patients with diffuse
      oesophageal spasm (DOS) remains controversial. The aim of this study was to
      assess functional results after extended myotomy for DOS. METHODS: This
      prospective study evaluated 20 patients who had extended myotomy (14 cm on the
      oesophagus and 2 cm below the oesophagogastric junction) with anterior
      fundoplication via a laparotomy for severe DOS. Median follow-up was 50 (range 6
      84) months. Functional data were assessed by means of dysphagia (range 0-3),
      chest pain (range 0-3) and overall clinical (range 0-12, including dysphagia,
      chest pain, regurgitation, gastro-oesophageal reflux) scores. RESULTS: All
      patients had severe DOS. The median preoperative overall clinical score was 6
      (range 3-8) with a dysphagia score of at least 2. Median postoperative functional
      scores were significantly lower than preoperative values (overall clinical score
      1 versus 6, dysphagia score 0 versus 3, chest pain score 0 versus 2). At final
      follow-up, good or excellent results were obtained for overall clinical score in
      16 patients, for dysphagia score in 18 and for chest pain score in all 20
      patients. Postoperative gastro-oesophageal reflux was noted in two of the 20
      patients. CONCLUSION: Extended myotomy with anterior fundoplication is an
      effective treatment for severe DOS. Medium-term postoperative functional results
      were excellent, especially in terms of dysphagia and chest pain.

PMID- 17497757
TI  - Risk factors in patients undergoing cricopharyngeal myotomy.
AB  - BACKGROUND: Cricopharyngeal myotomy for oropharyngeal dysphagia is designed to
      improve symptoms, but the operation can result in significant morbidity and even
      death. METHODS: : A retrospective analysis was carried out of all complications
      and deaths among 253 patients who had cricopharyngeal myotomy performed by a
      single surgeon. RESULTS: A single wound infection developed among 15 patients
      with neurological dysphagia. The same patient subsequently required laryngeal
      exclusion and tracheostomy. Of 139 patients treated for dysphagia secondary to
      muscular dystrophy, haematoma formation or infection occurred in four, and eight
      patients developed postoperative pulmonary complications, four of whom died from
      respiratory distress syndrome. Two patients with myogenic dysphagia required
      laryngeal exclusion with a permanent tracheostomy. Infection of the wound or
      retropharyngeal space was the main problem in 90 patients with a pharyngo
      oesophageal diverticulum, affecting 9 per cent of the patients. Fistula was
      documented in three patients overall (1.2 per cent). Systemic morbidity unrelated
      to the technique occurred in 26 patients (10.3 per cent). CONCLUSION: Pulmonary
      aspiration and lethal respiratory distress occurred only in patients with
      myogenic dysphagia. Local infection was the main complication in those with
      pharyngo-oesophageal diverticulum. Persistent aspiration can lead to laryngeal
      exclusion or resection with permanent tracheostomy.

PMID- 17497758
TI  - Validation and application of capillary electrophoresis for the analysis of
      lidocaine in a skin tape stripping study.
AB  - A fast and simple capillary zone electrophoresis method was developed and
      validated for the determination of lidocaine in skin using tape samples.
      Separation was performed in a 350 mm (265 mm to window) x 50 microm i.d. fused
      silica capillary using a background electrolyte of phosphoric acid-Tris pH 2.5.
      The extraction of lidocaine from tape samples was achieved using methanol, which
      was diluted to 50% with water before injection. Procaine was the internal
      standard. The migration times for procaine and lidocaine were 2.9 and 3.2 min,
      respectively. The limit of quantification for lidocaine was 50 microg, with
      signal to noise ratio greater than 10. The calibration curve was linear from 50
      to 1000 microg with r(2) greater than 0.99. The CV for both within- and between
      assay imprecision and the percentage of inaccuracy for the quality control
      samples including lower and upper limits of quantitation were <or=2% and <or=14%,
      respectively. The absolute recovery of lidocaine was >97%. The accuracy and
      selectivity of this method allowed the measurement of lidocaine in tape samples
      obtained from a skin tape stripping study of local anesthetics in healthy
      subjects.

PMID- 17497760
TI  - Human variability in hepatic and renal elimination: implications for risk
      assessment.
AB  - Hepatic metabolism and renal excretion constitute the main routes of xenobiotic
      elimination in humans. Improving human risk assessment for threshold contaminants
      requires the incorporation of quantitative data related to their elimination
      (toxicokinetics) and potential toxic effects (toxicodynamics). This type of data
      provides a scientific basis to replace the standard uncertainty factor (UF = 10)
      allowing for the consideration of human variability in toxicokinetics and
      toxicodynamics. This review focuses on recent research efforts aiming to
      incorporate human variability in hepatic and renal elimination (toxicokinetics)
      into the risk assessment process. A therapeutic drug database was developed to
      quantify pathway-related variability in human phase I and phase II hepatic
      metabolism as well as renal excretion in subgroups of the population (healthy
      adults, neonates and the elderly), using data on compounds cleared primarily
      through each route (> 60% dose). For each subgroup of the population and
      elimination route, pathway-related UFs were then derived to cover 95-99% of each
      subgroup. Overall, the default toxicokinetic UFs would not cover neonates, the
      elderly for most elimination routes and any subgroup of the population for
      compounds metabolized via polymorphic isozymes (such as CYP2C19 and CYP2D6).
      These pathway-related UFs allow the incorporation of in vivo metabolism and
      toxicokinetic data in the risk assessment process and provide a flexible
      intermediate option between the default UF and chemical-specific adjustment
      factors (CSAFs) derived from physiologically based pharmacokinetic models.
      Implications of human variability in hepatic metabolism and renal excretion for
      chemical risk assessment are discussed.

PMID- 17497759
TI  - The organophosphate-induced acute-phase response is characterized by synthesis of
      alpha 1-acid glycoprotein that exhibits an immunomodulatory effect.
AB  - The organophosphorus compounds soman and paraoxon induce the acute-phase (AP)
      response. All phases of the AP response, from macrophage activation and
      stimulation of glucocorticoid secretion to AP protein expression appear to be
      under the control of similar molecular mechanisms to those during the turpentine
      induced AP response. The AP protein content in the circulation 24 h after either
      soman, paraoxon or turpentine administration was injury-specific. Both soman and
      paraoxon poisoning were characterized by significantly increased synthesis of
      alpha(1)-acid glycoprotein (AGP) that displayed an immunomodulatory effect in
      vitro. This result suggests that after organophosphate poisoning AGP participates
      in vivo in a negative feedback mechanism that prevents over-activity of the
      immune system.

PMID- 17497761
TI  - Dynamics of p-terphenyl crystals at the phase transition temperature: a zero
      field EPR study of the photoexcited triplet state of pentacene in p-terphenyl
      crystals.
AB  - Pulsed zero-field electron paramagnetic resonance free induction decay (ZF EPR
      FID) techniques are employed to study the phase transition of p-terphenyl
      crystals (Tc = 193 K) by measuring selectively populated photoexcited triplet ZF
      transitions of dilute pentacene molecules in p-terphenyl single crystals. The
      sensitivity of ZF spectroscopy to small shifts in local magnetic fields enables
      the studies of guest-host configuration changes over a wide temperature range.
      Here we report the observation of guest pentacene (-h(14) and -d(14)) triplet ZF
      EPR FID spectra that disappear abruptly at Tc and of spectral broadening and
      shift below Tc. We interpret these spectral changes as evidence for guest
      couplings to host phenyl rings. Further, these data allow assignments of
      spectroscopic sites to crystallographic sites that occur in the phase transition.

PMID- 17497762
TI  - Dissociative double ionization of CO2: dynamics, energy levels, and lifetime.
AB  - In a kinematically complete experiment on the dissociative double ionization of
      CO2 by electron impact, spontaneous and metastable decay have been observed via
      the channel CO2(2+) --> CO+ + O+. The metastable decay shows a lifetime of 5.8 +/
      1.5 micros. The measured kinetic energy release spectrum of the dissociation
      shows one broad peak. To understand the observed features, ab initio potential
      energy surface (PES) for the ground electronic state of CO2(2+) was computed
      using a multireference configuration interaction method and a correlation
      consistent polarized-valence quadruple-zeta basis set, for a range of
      internuclear distances and O-C-O bond angles, and an analytic fit of the PES was
      obtained. The computed PES clearly indicates the metastability of the dication
      and yields a barrier height and an asymptotic limit in fair agreement with the
      reported data. A time-dependent quantum mechanical approach was used to compute
      the ground vibrational state wave function of CO2 in its ground electronic state.
      Assuming a Franck-Condon transition, the same function was taken to be the
      initial wave function at time t = 0 for the time evolution on the fitted PES for
      the ground electronic state of CO2(2+). The autocorrelation function was computed
      and Fourier transformed to obtain the excitation spectrum. Upon convolution with
      the instrument resolution function, the kinetic energy release spectrum was
      obtained, in good agreement with the experimental results, particularly at lower
      energies. The discrepancies at higher energies are attributed to the noninclusion
      of the excited states of CO2(2+) in the dynamical study.

PMID- 17497763
TI  - Computational study of thioflavin T torsional relaxation in the excited state.
AB  - Quantum-chemical calculations of the Thioflavin T (ThT) molecule in the ground S0
      and first excited singlet S1 states were carried out. It has been established
      that ThT in the ground state has a noticeable nonplanar conformation: the torsion
      angle phi between the benzthiazole and the dimethylaminobenzene rings has been
      found to be approximately 37 degrees. The energy barriers of the intramolecular
      rotation appearing at phi = 0 and 90 degrees are quite low: semiempirical AM1 and
      PM3 methods predict values approximately 700 cm-1 and ab initio methods
      approximately 1000-2000 cm(-1). The INDO/S calculations of vertical transitions
      to the S1(abs) excited state have revealed that energy ES1(abs) is minimal for
      the twisted conformation with phi = 90 degrees and that the intramolecular charge
      transfer takes place upon the ThT fragments' rotation from phi = 0 to 90 degrees.
      Ab initio CIS/RHF calculations were performed to find optimal geometries in the
      excited S1 state for a series of conformers having fixed phi values. The CIS
      calculations have predicted a minimum of the S1 state energy at phi approximately
      21 degrees; however, the energy values are 1.5 times overestimated in comparison
      to experimental data. Excited state energy dependence on the torsion angle phi,
      obtained by the INDO/S method, reveals that ES1(fluor) is minimal at phi =
      approximately 80-100 degrees, and a plateau is clearly observed for torsion
      angles ranging from 20 to 50 degrees. On the basis of the calculation results,
      the following scheme of photophysical processes in the excited S1 state of the
      ThT is suggested. According to the model, a twisted internal charge-transfer
      (TICT) process takes place for the ThT molecule in the excited singlet state,
      resulting in a transition from the fluorescent locally excited (LE) state to the
      nonfluorescent TICT state, accompanied by torsion angle phi growth from 37 to 90
      degrees. The TICT process effectively competes with radiative transition from the
      LE state and is responsible for significant quenching of the ThT fluorescence in
      low-viscosity solvents. For viscous solvents or when the ThT molecule is located
      in a rather rigid microenvironment, for example, when it is bound to amyloid
      fibrils, internal rotation in the dye molecule is blocked due to steric
      hindrance, which results in suppression of the LE --> TICT quenching process and
      in a high quantum yield of fluorescence.

PMID- 17497764
TI  - Conformational templates for rational drug design: flexibility of cyclo(D-Pro1
      Ala2-Ala3-Ala4-Ala5) in DMSO solution.
AB  - Long MD simulations (100 ns) for the important model cyclopentapeptide cyclo(D
      Pro1-Ala2-Ala3-Ala4-Ala5) were performed in explicit DMSO solution using both
      OPLS-AA and AMBER03 force fields. Simulations revealed conformational transitions
      between two main conformers, a predominant one (population 93-99%) and a minor
      conformer (population 0.4-6.7%). These results are in excellent agreement with 20
      experimental proton-proton distances estimated for this cyclopentapeptide. The
      previously discussed gamma-turn-like conformation for Ala4 was present only in a
      minor conformer.

PMID- 17497765
TI  - Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a
      cell- and caspase-based high-throughput screening assay. 3. Structure-activity
      relationships of fused rings at the 7,8-positions.
AB  - As a continuation of our efforts to discover and develop the apoptosis-inducing 4
      aryl-4H-chromenes as novel anticancer agents, we explored the SAR of fused rings
      at the 7,8-positions. It was found that a five-member aromatic ring, such as
      pyrrolo with nitrogen at either the 7- or 9-position, is preferred. A six-member
      aromatic ring, such as benzo or pyrido, also led to potent compounds. The SAR of
      the 4-aryl group was found to be similar for chromenes with a fused ring at the
      7,8-positions. These compounds were found to inhibit tubulin polymerization,
      indicating that cyclization of the 7,8-positions into a ring does not change the
      mechanism of action. Compound 2h was identified to be a highly potent apoptosis
      inducer with an EC50 of 5 nM and a highly potent inhibitor of cell proliferation
      with a GI50 of 8 nM in T47D cells.

PMID- 17497767
TI  - Dependence of the critical temperature on molecular parameters.
AB  - At the critical temperature the surface tension between coexisting liquid and
      vapor phases must be zero, and the repulsive contributions associated with cavity
      formation must exactly counterbalance those from interactions of a molecule in
      the cavity and the bulk. An expression for the critical temperature of pure
      fluids in terms of the parameters of scaled particle theory (SPT) has been
      obtained, and the calculated critical temperatures are compared with experimental
      data for a range of pure fluids. These include noble and diatomic gases, short
      and medium length hydrocarbons, aromatic compounds, halogenated compounds, oxygen
      containing compounds, and water. Considering the simplicity of this approach, a
      remarkably good correlation between calculated and experimental values is found
      for most of these fluids.

PMID- 17497766
TI  - Aqueous urea solutions: structure, energetics, and urea aggregation.
AB  - Urea is ubiquitously used as a protein denaturant. To study the structure and
      energetics of aqueous urea solutions, we have carried out molecular dynamics
      simulations for a wide range of urea concentrations and temperatures. The
      hydrogen bonds between urea and water were found to be significantly weaker than
      those between water molecules, which drives urea self-aggregation due to the
      hydrophobic effect. From the reduction of the water exposed urea surface area,
      urea was found to exhibit an aggregation degree of ca. 20% at concentrations
      commonly used for protein denaturation. Structurally, three distinct urea pair
      conformations were identified and their populations were analyzed by
      translational and orientational pair distribution functions. Furthermore, urea
      was found to strengthen water structure in terms of hydrogen bond energies and
      population of solvation shells. Our findings are consistent with a direct
      interaction between urea and the protein as the main driving force for protein
      denaturation. As an additional, more indirect effect, urea was found to enhance
      water structure, which would suggest a weakening of the hydrophobic effect.

PMID- 17497768
TI  - Theoretical study of the catalytic mechanism and metal-ion dependence of peptide
      deformylase.
AB  - The reaction pathway of deformylation catalyzed by E. coli peptide deformylase
      (PDF) has been investigated by the density functional theory method of PBE1PBE on
      a small model and by a two-layer ONIOM method on a realistic protein model. The
      deformylation proceeds in sequential steps involving nucleophilic addition of
      metal-coordinated water/hydroxide to the carbonyl carbon of the formyl group,
      proton transfer, and cleavage of the C-N bond. The first step is rate-determining
      for the deformylation, which occurs through a pentacoordinated metal center. The
      estimated activation energies with the ONIOM method are about 23.0, 15.0, and
      14.9 kcal/mol for Zn-, Ni-, and Fe-PDFs, respectively. These calculated barriers
      are in close agreement with experimental observations. Our results demonstrate
      that the preference for metal coordination geometry exerts a significant
      influence on the catalytic activity of PDFs by affecting the activation of the
      carbonyl group of the substrate, the deprotonation of the metal-coordinated
      water, and the stabilization of the transition state. This preference for
      coordination geometry is mainly determined by the ligand environment and the
      intrinsic electronic structures of the metal center in the active site of the
      PDFs.

PMID- 17497769
TI  - Conductivities, volumes, fluorescence, and aggregation behavior of ionic liquids
      [C4mim][BF4] and [C(n)mim]Br (n = 4, 6, 8, 10, 12) in aqueous solutions.
AB  - Densities, conductivities, and polarity indexes of pyrene for aqueous solutions
      of a series of ionic liquids [C(n)mim]Br (n = 4, 6, 8, 10, 12) and [C4mim][BF4]
      have been determined at 298.15 K as a function of ionic liquid concentrations. It
      was shown that possible aggregation appeared for the ionic liquids in aqueous
      solutions except for [C4mim]Br. The critical aggregation concentration (CAC) of
      the ionic liquids, the ionization degree of aggregates (beta), the standard Gibbs
      energy of aggregation (Delta G(m)(o)), the limiting molar conductivity
      (Lambda(m)(o)), and the standard partial molar volume (V(m)(o)) for the ionic
      liquids were derived from the experimental data. The dependence of the CAC, Delta
      G(m)(o), Lambda(m)(o), and V(m)(o) on the length of the alkyl chain of the
      cations was examined. It was further suggested from volumetric data that a
      micelle was formed for [C8mim]Br, [C10mim]Br, and [C12mim]Br in aqueous
      solutions. Their apparent molar volumes at the critical micelle concentration (V
      Phi,CMC), apparent molar volumes in the micelle phase (V(Phi)(mic)), and the
      change of their apparent molar volume upon micellization (Delta V Phi,m) were
      calculated by application of the pseudophase model of micellization. In addition,
      the average aggregation number of [C(n)mim]Br (n = 8, 10, 12) has been determined
      by the steady-state fluorescence quenching technique, and predicted from a simple
      geometrical mode. It is found that the experimental values are in good agreement
      with the predicted ones.

PMID- 17497770
TI  - On the performance of DFT and interatomic potentials in predicting the energetics
      of (three-membered ring-containing) siliceous materials.
AB  - We compare the enthalpies of transition for a range of SiO2 phases, including
      siliceous zeolites and dense polymorphs, calculated using three different
      interatomic potentials (Sanders-Leslie-Catlow (SLC), Sastre-Gale (SG), van Beest
      Kramers-van Santen (BKS)), and from B3LYP periodic DFT calculations, with the
      experimentally measured values. It is found that the calculated results show a
      linear correlation with the measured values but that they often either
      considerably underestimate or overestimate enthalpy differences compared to
      experiment. Care should thus be taken when comparing experimental and calculated
      results. A linear rescaling of the calculated enthalpies to put the data on the
      same energy scale is proposed. Furthermore, it is found that when comparing
      enthalpies of transitions for materials containing three-membered rings, for
      which there is no experimental data available, the values, rescaled to the
      experimental energy scale, are very similar for both DFT and interatomic
      potentials (except for the BKS potential). The latter result suggests that the
      energetics of three-membered ring containing materials is well described using
      both approaches. Finally, we discuss the transition enthalpies of four three
      membered ring containing siliceous materials and demonstrate that three-membered
      ring containing materials are not necessarily energetically disadvantageous but
      do become so progressively with increasing number of three-membered rings.

PMID- 17497771
TI  - Structure and stability of VO2+ in aqueous solution: a Car-Parrinello and static
      ab initio study.
AB  - Quantum chemical calculations have been carried out to get some insight
      concerning the effects of temperature and solvent acidity on the structure and
      stability of solvated VO2+ as the elementary chemical unit involved in the
      nucleation of vanadophosphates. First, because some recent theoretical studies
      have suggested a tendency of density functional theory (DFT) to favor lower
      coordination numbers for such systems, static calculations have been performed on
      [VO2(H2O)(4-n)]+.nH2O (n=0-2) conformers at the MP2 and DFT level of theory,
      using two different combinations of basis sets. The results of two pure-GGA (BP86
      and PBEPBE), two hybrid-GGA (PBE1PBE and mPWPW91), and two hybrid-meta-GGA
      (mPW1B95 and B1B95) functionals were analyzed on these systems. The comparison of
      the results indicates that the stability differences between the two
      methodologies are resolved when hydration energy is taken into account, provided
      that some amount of HF exchange is introduced in the DFT calculations. In a
      second step, Car-Parrinello simulations have been carried out starting from
      VO2(H2O)4+ surrounded by water molecules. The calculations at 300 K show the
      natural tendency of VO2(H2O)4+ to decompose to VO2(OH)2- and the requirements to
      work with an already acidified medium to be able to investigate the coordination
      sphere of VO2+ for an extended period of time. Under such conditions, we have
      obtained a clear preference for a five-coordinated vanadium. The molecular
      dynamics simulations performed at 500 K starting from hydrated VO2+ in a
      protonated medium found VO(OH)3 to be the most stable structure, whereas this
      ideal candidate for oxolation reactions is expected to be a very minor species at
      room temperature.

PMID- 17497772
TI  - Control of electronic and magnetic coupling via bridging ligand geometry in a
      bimetallic ytterbocene complex.
AB  - The ligand 1-methyl-3,5-bis(2,2':6',2' '-terpyridin-4'-yl)benzene has been
      employed in the synthesis of a new bimetallic ytterbocene complex [(Cp*)2Yb](1
      methyl-3,5-bis(2,2':6',2' '-terpyridin-4'-yl)benzene)[Yb(Cp*)2] (1) and the
      doubly oxidized congener [1]2+ in an attempt to determine the impact of the
      bridging ligand geometry on the magnetic/electronic properties as compared to the
      previously reported 1,4-analog [(Cp*)2Yb](1,4-di(terpyridyl)benzene)[Yb(Cp*)2]
      (2). Electrochemical, electronic, and magnetic data provide compelling evidence
      that the 1,3-geometry associated with the bridging ligand of 1 has done an
      effective job of inhibiting electronic communication between metal centers and
      magnetic coupling of spin carriers at room temperature as compared to 2. In fact,
      the physical data associated with 1 are quite similar to those reported for the
      monometallic analog (Cp*)2Yb(tpy) (3). In particular, the f-f profile of [1]2+ is
      nearly identical to that of [3]+ in its spectral features but with an almost
      exact doubling of the intensities. Further, the electronic coupling between metal
      centers as manifested in the potential separation between metal-based reduction
      waves has for the first time in these bimetallic ytterbocene complexes been found
      to go to zero for 1. Thus, the linkage isomerism at the phenyl coupling unit has
      induced a change in the ground-state electronic configuration from the singlet
      dianion-bridged (4f)13(pi*)2(4f)13 state found in 2 to the diradical-bridged
      (4f)13(piA*)1(piB*)1(4f)13 state in 1. This diradical formulation on the bridging
      ligand in 1 is supported by DFT calculations for the uncomplexed doubly reduced
      ligand that indicate the ground-state configuration is a singlet diradical state
      with the triplet-diradical state lying to slightly higher energy. Magnetic
      characterization of 1 is most consistent with the behavior previously observed
      for monometallic analogs such as 3, and there is no evidence of long-range
      magnetic ordering such as that observed for 2. In addition, X-ray
      crystallographic characterization of 1 represents the first case of a
      structurally characterized 2:1 metal-to-ligand adduct of the 1,3-bis(tpy)
      framework.

PMID- 17497774
TI  - Colloidal unilamellar layers of tantalum oxide with open channels.
AB  - Layered tantalum oxide, RbTaO3, was delaminated into colloidal TaO3 unilamellar
      crystallites, which are characterized by an open-channel structure as well as a
      very small thickness of approximately 1.0 nm.

PMID- 17497773
TI  - Optimized relaxivity and stability of [Gd(H(2,2)-1,2-HOPO)(H2O)]- for use as an
      MRI contrast agent.
AB  - Relaxometry and solution thermodynamic measurements show that Gd(H(2,2)-1,2-HOPO)
      is a good candidate as a contrast agent for magnetic resonance imaging (MRI-CA).
      Acidic, octadentate H(2,2)-1,2-HOPO forms a very stable Gd(III) complex
      [pGd=21.2(2)]. The coordination sphere at the Gd(III) center is completed by one
      water molecule that is not replaced by common physiological anions. In addition,
      this ligand is highly selective for Gd(III) binding in the presence of Zn(II) or
      Ca(II). The symmetric charge distribution of the 1,2-HOPO chelates is associated
      with favorably long electronic relaxation time T1,2e comparable to those of
      GdDOTA. This, in addition to the fast water exchange rate typical of HOPO
      chelates, improves the relaxivity to r1p=8.2 mM-1 s-1 (0.47 T). This remarkably
      high value is unprecedented for small-molecule, q=1 MRI-CA.

PMID- 17497776
TI  - Anion chelation by amido acid functionalized fused quartz/water interfaces
      studied by nonlinear optics.
AB  - We report resonantly enhanced surface second harmonic generation (SHG)
      measurements to track the interaction of the EPA priority toxic metal pollutant
      chromium(VI) with fused quartz/water interfaces containing tailor-made amino
      acids that serve as model systems for environmental and biological interfaces.
      chi3 measurements of amido acid functionalized fused quartz/water interfaces are
      consistent with two acid-base equilibria, suggesting the formation of a laterally
      hydrogen-bonded environment similar to what is observed for aliphatic carboxylic
      acids. Chromate adsorption isotherms recorded at pH 7 are suggestive of an
      intramolecular chelation mechanism that becomes important when four or more
      hydrogen-bonding moieties are displayed toward the incoming chromate. The strong
      binding affinities of the amido acid functionalized fused quartz/water interfaces
      toward chromate are consistent with nearly 50% slower transport rates with
      respect to free-flowing groundwater, indicating that, in the absence of redox
      processes, peptide materials in heterogeneous geochemical environments can
      significantly increase chromate residence times. The strong evidence for
      synergistic effects dominating the interactions of chromate with surface-bound
      amido acids indicates that chemical complexity can be systematically addressed
      using tailor-made organic surfaces and interfaces.

PMID- 17497777
TI  - Electromechanical phase transition in hexacyanometallate nanostructure (Prussian
      Blue).
AB  - This paper demonstrates the importance of the structural changeover in
      controlling the physical-chemical properties of hexacyanometalate-like materials
      (Prussian Blue). A meticulous in situ study of compositional variations using
      electroacoustic impedance techniques associated to electrogravimetric techniques
      in hexacyanoferrates containing K+ alkali metals reveals the existence of a
      nanostructural changeover coupled to a change of the magnetic properties of these
      electromagnetic materials. In the same way, the electroacoustic impedance
      techniques can be useful both in the understanding and in the in situ monitoring
      of the structural changeovers and the magnetic behavior of all kinds of
      materials.

PMID- 17497778
TI  - Highly sensitive nitric oxide detection using X-ray photoelectron spectroscopy.

PMID- 17497779
TI  - Metallodendrimers as transphosphorylation catalysts.

PMID- 17497780
TI  - Acyclic ribooxacarbenium ion mimics as transition state analogues of human and
      malarial purine nucleoside phosphorylases.
AB  - Transition state analogues of PNP, the Immucillins and DADMe-Immucillins, were
      designed to match transition state features of bovine and human PNPs,
      respectively. A third generation of inhibitors has been designed that contain an
      acyclic iminoalcohol to replace the cyclic mimic of the ribooxacarbenium ion at
      the transition states of PNPs. The best third generation inhibitor is equivalent
      to the best inhibitors found in the previous transition state analogues.

PMID- 17497781
TI  - Facile and E-selective intramolecular ring-closing metathesis reactions in 3(10)
      helical peptides: a 3D structural study.

PMID- 17497782
TI  - Pyromellitamide aggregates and their response to anion stimuli.
AB  - The N,N',N'',N'''-1,2,4,5-tetra(ethylhexanoate) pyromellitamide is found to be
      capable of both intermolecular aggregation and binding to small anions. It is
      synthesized by aminolysis of pyromellitic anhydride with ethanolamine, followed
      by a reaction with hexanoyl chloride. The single-crystal X-ray structure of the
      pyromellitamide shows that it forms one-dimensional columnar stacks through an
      intermolecular hydrogen-bonding network. It also forms self-assembled gels in
      nonpolar solvents, presumably by a hydrogen-bonding network similar to the solid
      state structure as shown by IR and XRD studies. Aggregation by intermolecular
      hydrogen bonding of the pyromellitamide is also observed by NMR and IR in
      solution. Fitting of NMR dilution data for pyromellitamide in d6-acetone to a
      cooperative aggregation model gave KE=232 M-1 and positive cooperativity of
      aggregation (rho=0.22). The pyromellitamide binds to a range of small anions with
      the binding strength decreasing in the order chloride>acetate>bromide>nitrate
      approximately iodide. The data indicate that the pyromellitamide binds two anions
      and that it displays negative cooperativity. The intermolecular aggregation of
      the pyromellitamide can also be altered using small anion stimuli; anion addition
      to preformed self-assembled pyromellitamide gels causes their collapse. The
      kinetics of anion-induced gel collapse are qualitatively correlated to the
      binding affinities of the same anions in solution. The cooperative anion binding
      properties and the sensitivity of the self-assembled gels formed by
      pyromellitamide toward anions could be useful in the development of sensors and
      switching/releasing devices.

PMID- 17497783
TI  - Unusual [2+4] and [2+2] cycloadditions of arenes in the confined cavity of self
      assembled cages.

PMID- 17497784
TI  - Synthesis of bulky phosphines by rhodium-catalyzed formal [2+2+2] cycloaddition
      reactions of tethered diynes with 1-alkynylphosphine sulfides.

PMID- 17497785
TI  - Aryl hydroxylation from a mononuclear copper-hydroperoxo species.

PMID- 17497786
TI  - A mixed-valent, Fe(II)Fe(I), diiron complex reproduces the unique rotated state
      of the [FeFe]hydrogenase active site.

PMID- 17497787
TI  - Cyclopolymerization of 1,6-heptadienes catalyzed by iron and cobalt complexes:
      synthesis of polymers with trans- or cis-fused 1,2-cyclopentanediyl groups
      depending on the catalyst.

PMID- 17497788
TI  - An electron-conducting cross-linked polyaniline-based redox hydrogel, formed in
      one step at pH 7.2, wires glucose oxidase.

PMID- 17497789
TI  - Facile quantification of lesions derived from 2'-deoxyguanosine in DNA.

PMID- 17497791
TI  - A keplerate magnetic cluster featuring an icosidodecahedron of Ni(II) ions
      encapsulating a dodecahedron of La(III) ions.

PMID- 17497790
TI  - Propagation of blood clotting in the complex biochemical network of hemostasis is
      described by a simple mechanism.

PMID- 17497792
TI  - Effect of the molecular mass and degree of substitution of oleoylchitosan on the
      structure, rheological properties, and formation of nanoparticles.
AB  - Oleoylchitosans (O-chitosans), with different molecular masses and degrees of
      substitution (DS), were synthesized by reacting chitosan with oleoyl chloride.
      The FT-IR suggested the formation of an amide linkage between amino groups of
      chitosan and carboxyl groups of oleic acid. The viscosity of O-chitosan sharply
      increased with the increase of concentration, whereas that of unmodified chitosan
      rose only slightly. This increase was stronger as the increase of hydrophobicity
      (DS) and molecular mass of the polymer. The critical aggregation concentration
      (CAC) of O-chitosans with DS 5, 11, and 27% were 79.43, 31.6, 10 mg/L,
      respectively, and the CAC of samples with molecular masses of 20, 38, 300, and
      1100 kDa were 50.1, 74.93, 125.9, and 630.9 mg/L, respectively. All of the O
      chitosans could reduce surface tension slightly. Nanoparticles were prepared
      using an O/W emulsification method. Mean diameters of the polymeric amphiphilic
      nanoparticles of O-chitosans with DS 5 and 11% were around 327.4 and 275.3 nm,
      respectively.

PMID- 17497793
TI  - Maceration enzymes and mannoproteins: a possible strategy to increase colloidal
      stability and color extraction in red wines.
AB  - Different strategies were adopted to achieve increases in color stability in
      Tempranillo wines: (i) addition of maceration enzymes directly to the must, (ii)
      addition of commercial mannoproteins to the must, and (iii) inoculation of must
      with yeast overexpressed of mannoproteins. The addition of enzymes favored color
      extraction, and the wines obtained presented higher values of wine color, color
      intensity, bisulfite-stable color, and visually enhanced color intensity. The
      enzyme hydrolytic activity produced an increase in the acid polysaccharide
      content and polyphenol index and yielded to wines with more astringency, tannin,
      and length. Added mannoproteins had clearer effects on the analyzed parameters
      than yeast. Contrary to what may be thought, mannoproteins did not maintain the
      extracted polyphenols in colloidal dispersion and neither ensured color
      stability. These compounds clearly modified the gustative structure of the wines,
      enhancing the sweetness and roundness.

PMID- 17497794
TI  - Alpha-amidation of cyclic ethers catalyzed by simple copper salt and a mild and
      efficient preparation method for alpha,omega-amino alcohols.
AB  - Copper(II) trifluoromethanesulfonate catalyzed the amidation of cyclic ethers
      with iminoiodanes under mild conditions (CH2Cl2, 40 degrees C) with good yields
      (up to 86% based on 97% conversion) and selectivity (only alpha-amino products
      were found). Subsequently, the tosylamidated products could undergo a reductive
      ring-opening reaction to give alpha,omega-amino alcohols.

PMID- 17497795
TI  - Catalytic enantioselective Friedel-Crafts alkylations of indoles with alpha'
      phosphoric enones.
AB  - The C2-symmetric bis(oxazoline) copper(II) complex proves to be an excellent
      catalyst in the Friedel-Crafts alkylation of indoles with alpha'-phosphoric
      enones. The enantioselectivities of this reaction are obtained in up to 98% ee.

PMID- 17497796
TI  - Highly enantioselective synthesis of gamma-hydroxy-alpha,beta-acetylenic esters
      catalyzed by a beta-sulfonamide alcohol.
AB  - This work concerns the asymmetric addition of methyl propiolate to aldehydes with
      1,2-dimethoxyethane (DME) as additive and beta-sulfonamide alcohol titanium
      complex as a catalyst. The reactions proceeded under mild conditions and gave the
      highly functionalized chiral propargylic alcohols with high ee values and good
      yields. Differences between three types of ligands have also been discussed.

PMID- 17497797
TI  - Rigid pi-conjugated mono-, bis-, and tris(2,2':6',2' '-terpyridines).
AB  - A set of rigid, pi-conjugated linear mono- and bisterpyridines and star-shaped
      tristerpyridines have been synthesized using Pd(0)-catalyzed coupling reactions
      and the Horner-Wadsworth-Emmons reaction. The terpyridyl ligands obtained feature
      strong emission in the blue range with high quantum yields in dilute solution and
      thin films.

PMID- 17497798
TI  - Asymmetric synthesis of syn-alpha-substituted beta-amino ketones by using
      sulfinimines and prochiral Weinreb amide enolates.
AB  - Syn-alpha-substituted beta-amino Weinreb amides are new chiral building blocks
      for asymmetric synthesis of syn-alpha-substituted beta-amino acids, aldehydes,
      and ketones and are prepared by addition of prochiral lithium enolates of Weinreb
      amides to sulfinimines (N-sulfinyl imines).

PMID- 17497799
TI  - Cocrystal or salt: does it really matter?
AB  - A structural analysis of over 80 salts and cocrystals synthesized from equimolar
      amounts of carboxylic acids and N-heterocycles demonstrates that salt formation
      as a result of proton transfer from the acid to the base frequently (11/24; 45%)
      results in a lattice with an unpredictable chemical (solvate) or stoichiometric
      composition. However, if no proton transfer takes place and the result is a
      molecular cocrystal, a crystal lattice with an unexpected chemical content or
      stoichiometry is much less likely (3/61; 5%). These results indicate that the
      process of converting a neutral carboxylic acid into a carboxylate anion can have
      important structural consequences that make structure prediction and targeted
      supramolecular synthesis of salts much more difficult than of cocrystals.
      Consequently, cocrystals may offer new opportunities for producing a greater
      diversity of solid forms of drug substances that exhibit the appropriate balance
      of critical properties for development into a viable and effective drug product.

PMID- 17497800
TI  - Synthesis of alpha- and beta-glycosyl isothiocyanates via oxazoline
      intermediates.
AB  - A practical synthesis of acylated glycosyl isothiocyanates from sugar oxazolines,
      by reaction with thiophosgene, is reported. In the absence of any additive, the
      reaction is governed by the reverse anomeric effect, leading to the equatorially
      oriented isothiocyanate. However, in the presence of copper(II) chloride, the
      reaction proceeds preferentially with retention of the configuration at the
      anomeric center, providing the axial anomer as the major product. Noteworthy,
      this strategy allows accessing per-O-acetylated glycopyranosyl isothiocyanates
      with 1,2-cis relative configuration (e.g., the alpha-anomer in the D-gluco and D
      galacto series), a problem that was outside the scope of previous methodologies.

PMID- 17497801
TI  - Chiral macrocycle-catalyzed highly enantioselective phenylacetylene addition to
      aliphatic and vinyl aldehydes.
AB  - The 1,1'-binaphthyl macrocycle (S)-2 is found to be an excellent catalyst for the
      alkyne addition to aldehydes. In the presence of (S)-2 (20 mol %) and Me2Zn (2
      equiv) in THF at room temperature, the addition of phenylacetylene to linear or
      branched aliphatic aldehydes and vinyl aldehydes gave various propargylic
      alcohols with 89-96% ee.

PMID- 17497802
TI  - A highly selective rearrangement of a housane-derived cation radical: an
      electrochemically mediated transformation.
AB  - To utilize housane-derived cation radicals as intermediates for the synthesis of
      the bicyclo (n.3.0) framework of natural products, a highly regioselective [1,2]
      shift of carbon to either a radical or an electron-deficient site is required.
      Herein we describe how this has been accomplished, provide a set of guidelines to
      assess housane oxidizability prior to its synthesis, and describe a synthesis of
      housane 18 that capitalizes upon the facility of [1,5] hydrogen shifts in
      substituted cyclopentadienes. The catalytic electrochemically mediated oxidation
      of 18 leads to a cation radical that engages in a rearrangement leading to the
      (4.3.0) adduct 23. The appearance of a catalytic current in the cyclic
      voltammogram of a solution containing the tris(aryl)amine and housane 18 is an
      excellent indicator that the amminium cation radical 14*+ is able to oxidize the
      housane and return the mediator to the original redox couple. DFT calculations
      show electron density on both the aryl and strained sigma framework in the HOMO
      of housane 18. From the spin density and electrostatic potential map for the
      cation radical, a picture where the spin resides on the side that is distal to
      the substituent emerges, while the hole is proximal to it. Both experiment and
      theory show that the rearrangement is best characterized as a [1,2] carbon shift
      toward an electron-deficient site and that migration toward the substituent
      bearing carbon is much preferred over the alternative pathway.

PMID- 17497803
TI  - Palladium(0)-catalyzed, copper(I)-mediated coupling of boronic acids with cyclic
      thioamides. selective carbon-carbon bond formation for the functionalization of
      heterocycles.
AB  - The palladium-catalyzed cross-coupling of cyclic thioamides with arylboronic
      acids in the presence of stoichiometric amounts of a copper(I) cofactor is
      described. The desulfitative carbon-carbon cross-coupling protocol is performed
      under neutral conditions and can be applied to a range of heterocyclic structures
      with embedded thioamide fragments. Successful carbon-carbon cross-coupling is
      independent of the ring size, aromaticity/nonaromaticity, the presence of
      additional heteroatoms, or other functional groups in the starting thioamide
      structure. Employing controlled microwave irradiation at 100 degrees C, most
      cross-couplings can be completed within 2 h and proceed in high yields. An
      advantage of using thioamides as starting materials is the fact that the system
      can be tuned to an alternative carbon-sulfur cross-coupling pathway by changing
      to stoichiometric copper(II) under oxidative conditions. Both types of thioamide
      cross-couplings are orthogonal to the traditional base-catalyzed Suzuki-Miyaura
      cross-coupling of aryl halides with boronic acids.

PMID- 17497804
TI  - Synthesis of kaempferitrin.
AB  - A short synthesis of Kaempferitrin (1), a 3,7-diglycosylflavone, is reported. Key
      features include the synthesis of a protected form of kaempferol in which all
      four hydroxy groups are differentiated and the first bis-glycosylation of a
      dihydroxyflavone. This synthesis will allow the preparation of derivatives for
      further explorations into the origins of this compound's biological activity.

PMID- 17497805
TI  - Methylpentanediolborane: easy access to new air- and chromatography-stable,
      highly functionalized vinylboronates.
AB  - Methylpentanediolborane (MPBH) 1 can be prepared easily by reaction of
      hexyleneglycol with BH3/DMS or B2H6 generated from NaBH4 and I2. MPBH
      hydroborates stereo- and regioselectively highly functionalized alkynes,
      including propargyl bromide and propionaldehyde acetal. MPBH compares favorably
      with pinacolborane in terms of reactivity. The obtained vinylboronic esters are
      air- and chromatography-stable.

PMID- 17497806
TI  - Self-assembling cannabinomimetics: supramolecular structures of N-alkyl amides.
AB  - Certain fatty acid N-alkyl amides from the medicinal plant Echinacea activate
      cannabinoid type-2 (CB2) receptors. In this study we show that the CB2-binding
      Echinacea constituents dodeca-2E,4E-dienoic acid isobutylamide (1) and dodeca
      2E,4E,8Z,10Z-tetraenoic acid isobutylamide (2) form micelles in aqueous medium.
      In contrast, micelle formation is not observed for undeca-2E-ene-8,10-diynoic
      acid isobutylamide (3), which does not bind to CB2, or structurally related
      endogenous cannabinoids, such as arachidonoyl ethanolamine (anandamide). The
      critical micelle concentration (CMC) range of 1 and 2 was determined by
      fluorescence spectroscopy as 200-300 and 7400-10000 nM, respectively. The size of
      premicelle aggregates, micelles, and supermicelles was studied by dynamic light
      scattering. Microscopy images show that compound 1, but not 2, forms globular and
      rod-like supermicelles with radii of approximately 75 nm. The self-assembling N
      alkyl amides partition between themselves and the CB2 receptor, and aggregation
      of N-alkyl amides thus determines their in vitro pharmacological effects.
      Molecular mechanics by Monte Carlo simulations of the aggregation process support
      the experimental data, suggesting that both 1 and 2 can readily aggregate into
      premicelles, but only 1 spontaneously assembles into larger aggregates. These
      findings have important implications for biological studies with this class of
      compounds.

PMID- 17497807
TI  - Anti-inflammatory thiazine alkaloids isolated from the New Zealand ascidian
      Aplidium sp.: inhibitors of the neutrophil respiratory burst in a model of gouty
      arthritis.
AB  - Ascidiathiazones A (3) and B (4), two new tricyclic thiazine-containing
      quinolinequinone alkaloids, were isolated from the New Zealand ascidian Aplidium
      species. Both compounds inhibited the in vitro production of superoxide by PMA
      stimulated human neutrophils in a dose-dependent manner with IC50 1.55 +/- 0.32
      and 0.44 +/- 0.09 microM, respectively. In vivo inhibition of superoxide
      production by peritoneal neutrophils in a murine model of gout was observed for
      both compounds with oral doses of 25.6 micromol/kg. Ascidiathiazone A (3) was
      synthesized in four steps from 8-hydroxyquinoline-2-carboxylic acid.

PMID- 17497808
TI  - Oleanane saponins from Stylosanthes erecta.
AB  - Five new oleanane saponins (1-5) together with four know flavonol glycosides were
      isolated from the aerial parts of Stylosanthes erecta. Their structures were
      elucidated by 1D and 2D NMR experiments including 1D-TOCSY, DQF-COSY, ROESY,
      HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The aglycone moieties of
      1-4 were assigned as new oleanane derivatives.

PMID- 17497810
TI  - Self-assembly of a Rh(I) complex on Au(111) surfaces and its electrocatalytic
      activity toward the hydrogen evolution reaction.
AB  - The self-assembly of a Wilkinson type of catalyst molecule, trans
      RhCl(CO)(PPh3)2, on Au(111) surfaces and its electrocatalytic properties toward
      the hydrogen evolution reaction (HER) are investigated by employing scanning
      tunneling microscopy (STM), cyclic voltammetry (CV), and X-ray photoelectron
      spectroscopy (XPS). The self-assembled monolayers of RhCl(CO)(PPh3)2 are prepared
      from either dichloromethane or aqueous solutions, but the ordered structures are
      observed only in atmospheric conditions after solvents evaporate. In the
      electrolyte solutions, disordered yet uniformly sized spherical clusters of
      individual molecules are observed as a result of the conformational change of the
      molecule by the solvation effect of water. The immobilized Rh(I) molecular
      clusters are electrochemically stable in a wide potential window and exhibit
      remarkable electrocatalytic activity toward HER in perchloric acid solutions.
      Several comparative experiments involving similar types of immobilized complexes
      containing Ru(I) and Ir(I) centers and solution species of RhCl(CO)(PPh3)2 are
      performed. However, none of them are found to be electroactive to HER. The Tafel
      slope of HER on the Rh(I) complex modified Au(111) electrode in 0.1 M HClO4 is
      determined to be -0.061 V, which is almost in the middle of those on bare Au(111)
      (-0.093 V) and Rh covered (thetaRh approximately 0.3) Au(111) (-0.034 V)
      electrodes. XPS measurements reveal a valence change of Rh(I) to Rh(0), and an
      oxidative addition and reductive elimination mechanism is suggested for the
      enhancement of HER.

PMID- 17497809
TI  - Alboatisins A-C, ent-atisene diterpenoids from Isodon albopilosus.
AB  - Three biogenetically interesting ent-kaurane-derived metabolites, alboatisins A-C
      (1-3), featuring a C-13-oxygenated ent-atisane skeleton, have been isolated from
      the aerial parts of Isodon albopilosus. Their structures were determined on the
      basis of spectroscopic evidence. Compound 2 exhibited cytotoxicity against A549
      and HT-29 human cancer cells, with IC50 values of 8.3 and 7.9 microM,
      respectively.

PMID- 17497811
TI  - Construction of hybrid bilayer membrane (HBM) Biochips and characterization of
      the cooperative binding between cytochrome-c and HBM.
AB  - We constructed multi-channel hybrid bilayer membrane (HBM) biochips and
      characterized them by surface plasmon resonance imaging. Each channel in the
      biochip was prepared using vesicles with different proportions of negative,
      neutral, and positive lipids. The HBM surfaces were tested by interaction with
      two globular proteins that recognize surfaces covered with opposite charges.
      Spots modified with the same HBM show responses within a relative standard
      deviation of 10% or smaller. These devices were also used to study in detail the
      interaction between cytochrome-c (cyt-c) and HBMs. Cooperative binding between
      cyt-c and negative HBMs was demonstrated. Using an adaptation of the Hill model,
      we calculated a Hill coefficient of 5 and a 10-fold increase in the binding
      constant with the increase in cyt-c concentration. We propose that this treatment
      can be used to evaluate the cooperative binding of surface proteins to membranes.

PMID- 17497812
TI  - Ion exchange in catanionic mixtures: from ion pair amphiphiles to surfactant
      mixtures.
AB  - We have studied concentrated equimolar mixtures of tetradecanoic acid (myristic
      acid, C13COOH) and hexadecyltrimethylammonium hydroxide (CTAOH) in which the OH-
      counterions are gradually exchanged by other anions (Cl-, Br-, CH3COO-, CH3
      (C6H4)-SO3-). We demonstrate that the stability of a Lbeta phase can be achieved
      at equimolarity between both surfactants, provided that the phase contains also a
      sufficient number of anions exchanged with OH-. In the absence of exchange
      (equimolar mixture of C13COOH and CTAOH), a three-dimensional crystalline Lc
      phase is produced. As the OH- ions are replaced by other ions, a swollen Lbeta
      lamellar phase appears, first in coexistence with the Lc (D* = 400 A) and then in
      coexistence with a dilute phase only (D* = 215 A). In the latter regime, the
      repeating distance depends very little on the exchange ratio, but rather on the
      nature of the counterion. If too many OH- ions are exchanged, the Lbeta phase
      becomes unstable again. A Poisson-Boltzmann model with charge regulation computed
      for a closed system predicts qualitatively the existence of this narrow domain of
      stability for the Lbeta phase.

PMID- 17497813
TI  - Construction of a comb-like glycosylated membrane surface by a combination of UV
      induced graft polymerization and surface-initiated ATRP.
AB  - Carbohydrate residues are found on the extracellular side of the cell membrane.
      They form a protective coating on the outer surface of the cell and are involved
      in intercellular recognition. Synthetic carbohydrate-based polymers, so-called
      glycopolymers, are emerging as important well-defined tools for investigating
      carbohydrate-based biological processes and for simulating various functions of
      carbohydrates. In this work, the surface of a polypropylene microporous membrane
      (PPMM) was modified with comb-like glycopolymer brushes by a combination of UV
      induced graft polymerization and surface-initiated atom-transfer radical
      polymerization (ATRP). 2-Hydroxyethyl methacrylate (HEMA) was first grafted to
      the PPMM surface under UV irradiation in the presence of benzophenone and ferric
      chloride. ATRP initiator was then coupled to the hydroxyl groups of poly(HEMA)
      brushes. Surface-initiated ATRP of a glycomonomer, D-gluconamidoethyl
      methacrylate, was followed at ambient temperature in aqueous solvent. Water had a
      significant acceleration effect on the ATRP process; however, loss of control
      over the polymerization process was also observed. The addition of CuBr2 to the
      ATRP system largely increased the controllability at the cost of the
      polymerization rate. The grafting of HEMA, the coupling of ATRP initiator to the
      hydroxyl groups, and the surface-initiated ATRP were confirmed by Fourier
      transform infrared spectroscopy and X-ray photoelectron spectroscopy.

PMID- 17497814
TI  - Morphological and structural evolution of mesoporous silicas in a mild buffer
      solution and lysozyme adsorption.
AB  - Mesoporous silicas with various morphologies and structures were synthesized with
      the aid of 2,2,4-trimethylpentane (TMP) in the presence of nonionic surfactant
      P123 [(EO)20(PO)70(EO)20] as a structure-directing agent under mild reaction
      conditions (HAc-NaAc buffer solution, pH 4.4). The ropelike particles formed by
      end-to-end interconnected nanorods were obtained at a TMP/P123 weight ratio of
      0.5. It is noteworthy to mention that the mesoporous nanorods have channels
      running parallel to the short axis. The silica hollow spheres can be obtained at
      a higher TMP/P123 weight ratio because of the fusion of the primary nanorods
      around the interface of the O/W emulsion. Initial synthesis temperatures of 15,
      25, and 40 degrees C can lead to mesoporous silicas with highly ordered 2D
      hexagonal mesostructure, vesicular mesostructure, and mesostructured cellular
      foams (MCF), respectively. The mesoporous silicas exhibit high adsorption
      capacity (up to 536 mg g(-1)) and very rapid (<5 min to reach equilibrium)
      lysozyme immobilization. More importantly, it is revealed that mesoporous silica
      hollow spheres with rugged surfaces can greatly accelerate the adsorption rate of
      the enzyme during the adsorption process.

PMID- 17497815
TI  - Cassie-Wenzel wetting transition in vibrating drops deposited on rough surfaces:
      is the dynamic Cassie-Wenzel wetting transition a 2D or 1D affair?
AB  - The transition between the Cassie and Wenzel wetting regimes has been observed
      under vertical vibration of a water drop placed on a rough micrometrically scaled
      polymer pattern. The transition takes place under the constant force per unit
      length of the triple contact line, not under constant pressure. A study of the
      vibrating drop deposited on the rough surface supplied valuable information
      concerning the Cassie-Wenzel wetting transition.

PMID- 17497816
TI  - Optical switching of porphyrin-coated silicon nanowire field effect transistors.
AB  - We study porphyrin derivative coated silicon nanowire field effect transistors
      (SiNW-FETs), which display a large, stable, and reproducible conductance increase
      upon illumination. The efficiency and the kinetics of the optical switching are
      studied as a function of gate voltage, illumination wavelength, and temperature.
      The decay kinetics from the high- to the low-conductance state is governed by
      charge recombination via tunneling, with a rate depending on the state of the
      SiNW-FET. The comparison to porphyrin-sensitized carbon nanotube FETs allows the
      environment- and molecule-dependent photoconversion process to be distinguished
      from the charge-to-current transducing effect of the semiconducting channel.

PMID- 17497817
TI  - Triplet state absorption in carbon nanotubes: a TD-DFT study.
AB  - We predict properties of triplet excited states in single-walled carbon nanotubes
      (CNTs) using a time-dependent density-functional theory (TD-DFT). We show that
      the lowest triplet state energy in CNTs to be about 0.2-0.3 eV lower than the
      lowest singlet state energies. Like in pi-conjugated polymers, the lowest CNT
      triplets are spatially localized. These states show strong optical absorption at
      about 0.5-0.6 eV to the higher lying delocalized triplet states. These results
      demonstrate striking similarity of the electronic features between CNTs and pi
      conjugated polymers and provide explicit guidelines for spectroscopic detection
      of CNT triplet states.

PMID- 17497818
TI  - Electrically assisted magnetic recording in multiferroic nanostructures.
AB  - We demonstrate the room-temperature control of magnetization reversal with an
      electric field in an epitaxial nanostructure consisting of ferrimagnetic
      nanopillars embedded in a ferroelectric matrix. This was achieved by combining a
      weak, uniform magnetic field with the switching electric field to selectively
      switch pillars with only one magnetic configuration. On the basis of these
      experimental results, we propose to use an electric field to assist magnetic
      recording in multiferroic systems with high perpendicular magnetic anisotropy.

PMID- 17497819
TI  - Atomic structure of graphene on SiO2.
AB  - We employ scanning probe microscopy to reveal atomic structures and nanoscale
      morphology of graphene-based electronic devices (i.e., a graphene sheet supported
      by an insulating silicon dioxide substrate) for the first time. Atomic resolution
      scanning tunneling microscopy images reveal the presence of a strong spatially
      dependent perturbation, which breaks the hexagonal lattice symmetry of the
      graphitic lattice. Structural corrugations of the graphene sheet partially
      conform to the underlying silicon oxide substrate. These effects are obscured or
      modified on graphene devices processed with normal lithographic methods, as they
      are covered with a layer of photoresist residue. We enable our experiments by a
      novel cleaning process to produce atomically clean graphene sheets.

PMID- 17497821
TI  - Three-layer core/shell structure in Au-Pd bimetallic nanoparticles.
AB  - This paper describes the internal structure of Au-Pd nanoparticles exhibiting
      newly discovered three-layer core/shell morphology, which is composed of an
      evenly alloyed inner core, an Au-rich intermediate layer, and a Pd-rich outer
      shell. By exploitation of spatially resolved imaging and spectroscopic and
      diffraction modes of transmission electron microscopy (TEM), insights were gained
      on the composition of each one of the observed three layers, indicating a
      significant extent of intimate alloy among the monometallic elements.

PMID- 17497820
TI  - Simulations and analysis of self-assembly of CdTe nanoparticles into wires and
      sheets.
AB  - Recent experiments have reported the self-assembly of TGA- and DMAET-stabilized
      CdTe nanoparticles (NPs) into wires and sheets, respectively, depending upon the
      stabilizer used. We develop a mesoscale model based on quantum mechanical
      calculations and perform Monte Carlo simulations of these NPs to elucidate the
      conditions under which these two structures will form. We show that consideration
      of NP shape, directional attraction, and electrostatic interactions is key to
      determining the anisotropy of the NP-NP interaction and final self-assembled
      structures.

PMID- 17497822
TI  - Macroscopic tuning of nanomechanics: substrate bending for reversible control of
      frequency and quality factor of nanostring resonators.
AB  - We have employed a chip-bending method to exert continuous and reversible control
      over the tensile stress in doubly clamped nanomechanical beam resonators. Tensile
      stress is shown to increase the quality factor of both silicon nitride and single
      crystal silicon resonators, implying that added tension can be used as a general,
      material-independent route to increased quality factor. With this direct
      stretching technique, we demonstrate beam resonators with unprecedented
      tunability of both frequency and quality factor. Devices can be tuned back and
      forth between a high and low stress state, with frequency tunability as large as
      several hundred percent demonstrated. Over this wide range of frequency, quality
      factor is also tuned by as much as several hundred percent, providing insights
      into the loss mechanisms in these materials and this class of nanoresonator.
      Devices with frequencies in the 1-100 MHz range are studied, with quality factor
      as high as 390,000 achieved at room temperature, for a silicon nitride device
      with cross-sectional dimensions below 1 microm, operating in a high stress state.
      This direct stretching technique may prove useful for the identification of loss
      mechanisms that contribute to the energy balance in nanomechanical resonators,
      allowing for the development of new designs that would display higher quality
      factors. Such devices would have the ability to resolve smaller addendum masses
      and thus allow more sensitive detection and offer the potential for providing
      access to previously inaccessible dissipation regimes at low temperatures. This
      technique provides the ability to dramatically tune both frequency and quality
      factor, enabling future mechanical resonators to be used as variable frequency
      references as well as variable band-pass filters in signal-processing
      applications.

PMID- 17497823
TI  - Two particle enhanced nano Raman microscopy and spectroscopy.
AB  - The distance- and polarization-dependent near-field enhancement of two coupling
      metal nanoparticles (MNPs) is analyzed by means of the novel scanning particle
      enhanced Raman spectroscopy (SPRM) technique. In contrast to single MNP Raman
      experiments, the near-field coupling between two dissimilar MNPs as followed here
      leads to a Raman hot spot yielding an extra enhancement factor of 17.6 and 20, as
      proven here both in experiment and in theory. Three-dimensional electric field
      calculations for our two-particle arrangements were performed using the
      semianalytical multiple-multipole method. An excellent agreement is found to our
      experiments, in which we inspect the interaction between a "scanning" 30 nm gold
      MNP (Au30) and a "fixed" 80 nm Au MNP (Au80). The Au80 MNP is attached to the
      apex of an optical fiber manipulator and exposed to the Gaussian focus of a high
      NA = 1.45 objective at lambda = 532 nm. A monolayer of 1-octanethiol molecules
      covering the Au80 MNP serves as the electric field prober when scanning the Au30
      MNP through the optical focus. This constellation allows recording the Raman
      signatures from a very low number of well-confined molecules. Moreover, also the
      spectral and spatial dependence could be explored with a superb sensitivity and
      very low integration time.

PMID- 17497824
TI  - Fluorescent ion-selective nanosensors for intracellular analysis with improved
      lifetime and size.
AB  - We describe the synthesis and characterization of sodium-selective polymeric
      nanosensors that improves upon the lifetime and size of previous fiberless
      nanosensors. Sonication is used to form the polymer nanospheres that contain all
      the components needed for ion sensing. Even though the size is small
      (approximately 120 nm), the lifetime of these sensors in solution is on the order
      of a week. The surface coating has also been optimized for stability,
      biocompatibility, and ease of chemical modification.

PMID- 17497825
TI  - A self-templated approach to TiO2 microcapsules.
AB  - A self-templated approach has been developed for the synthesis of TiO2
      microcapsules with tunable size and wall thickness by heating sol-gel derived
      TiO2 microspheres with poly(acrylic acid) (PAA) in a diethylene glycol (DEG)
      solution. PAA plays a crucial role in the formation of microcapsules by
      crosslinking the surface TiO2 nanoparticles and preventing them from dissolution
      by DEG. Hollow microcapsules form when DEG molecules penetrate the outer layer
      and remove the core materials by forming soluble titanium glycolate.

PMID- 17497826
TI  - Simple method for identification of metallothionein isoforms in cultured human
      prostate cells by MALDI-TOF/TOF mass spectrometry.
AB  - The present paper describes a rapid method for identification and
      characterization of human metallothionein (MT) isoforms in complex cell cultures
      using high-resolution matrix-assisted laser desorption/ionization time-of
      flight/time-of-flight mass spectrometry (MALDI-TOF/TOF). In the proposed method,
      the sample preparation of MTs from cultured cells is both simple and fast. It is
      accomplished by trypsin cleavage of cell proteins into small peptide species, the
      majority of which are subsequently removed by gel filtration using beads with an
      exclusion limit of 4000 Da. In contrast to most cell proteins, MTs remain intact
      (undigested) upon being treated with trypsin, being excluded by the gel beads and
      thus recovered by low-speed centrifugation. To identify the protein constitutes
      of the MT preparation, the MT sample is divided into two parts, one for intact
      protein accurate mass measurement, the other for tryptic digestion followed by MS
      and MS/MS analyses. In the latter case, the MT proteins are denatured by the
      addition of EDTA which strips heavy metals from MTs and renders them susceptible
      to tryptic digestion. The obtained accurate mass with the unique peptide
      sequences of each MT isoform allows for unambiguous identification of MT isoforms
      in the prepared mixture. The method has been applied to RWPE-1 cells derived from
      normal human prostate epithelium. Four MT isoforms, 1E, 1G, 1X, and 2A, have been
      confidently identified, being primarily acetylated at N-termini. These results
      are in agreement with the expression of MT mRNAs in RWPE-1 cells determined by
      real-time reverse-transcription polymerase chain reaction (RT-PCR).

PMID- 17497827
TI  - Inline injection microdevice for attomole-scale sanger DNA sequencing.
AB  - A new affinity-capture-based inline purification, concentration, and injection
      method is developed for microchip capillary electrophoresis (CE) and used to
      perform efficient attomole-scale Sanger DNA sequencing separations. The
      microdevice comprises three axial domains for nanoliter-scale sequencing sample
      containment, sample plug formation, and high-resolution capillary gel
      electrophoresis. Purified and concentrated inline sample plugs are formed by
      electrophoretically driving Sanger sequencing extension fragments into an
      affinity-capture polymer network positioned within a CE separation channel.
      Extension fragments selectively hybridize and concentrate at the polymer
      interface while residual primer, nucleotides, and salts electrophorese out of the
      system. The plug is thermally released and injected into the CE channel by direct
      application of the separation voltage. To evaluate this system, 30 nL of
      sequencing sample prepared from 100 amol (60 million molecules) of human
      mitochondrial hypervariable region II amplicon was introduced into the microchip,
      purified, concentrated, and injected, generating a read length of 365 bases with
      99% accuracy. This efficient inline injection system obviates the need for the
      excess sample that is required by cross-injection techniques, thereby enabling
      Sanger sequencing and other high-performance genetic analysis using DNA
      quantities approaching theoretical detection limits.

PMID- 17497828
TI  - High-throughput cytochrome P450 inhibition assays using laser diode thermal
      desorption-atmospheric pressure chemical ionization-tandem mass spectrometry.
AB  - This paper describes the development of a high-throughput method for the analysis
      of cytochrome P450 (CYP) inhibition assay incubation samples using laser diode
      thermal desorption interfaced with atmospheric pressure chemical ionization mass
      spectrometry (LDTD-APCI-MS). Data for the CYP isoforms 3A4, 2D6, 2C9, and 1A2
      from competitive inhibition assays are shown. The potential for inhibition of the
      CYP isoforms was measured by monitoring the level of the metabolites 6beta
      hydroxytestosterone (3A4), dextrorphan (2D6), 4'-hydroxydiclofenac (2C9), and
      acetaminophen (1A2) formed in the presence of drug candidates using an eight
      point titration. The analytical method involves plating of the inhibition samples
      on specially designed 96-well plates with stainless steel bottoms, followed by
      direct analysis using the LDTD source. Validation of the LDTD-MS method was
      performed by testing for interferences, reproducibility, dynamic range, ion
      suppression, and the ability of the source to produce comparable results to
      previously validated LC-MS methods. IC50 values for each CYP isoform using 33
      different test compounds showed excellent agreement between LDTD-APCI-MS and LC
      MS methods and literature values where available. Assay analysis time using the
      LDTD-APCI source is reduced to less than 30 min for a single 96-well plate
      compared to greater than 10 h using the LC-MS method. The LDTD-APCI-MS and LC-MS
      methods and results are compared and limitations and future potential for LDTD
      APCI-MS are discussed.

PMID- 17497829
TI  - Photonic crystal surface waves for optical biosensors.
AB  - We present a new optical biosensor technique based on registration of dual
      optical s-polarized modes on a photonic crystal surface. The simultaneous
      registration of two optical surface waves with different evanescent depths from
      the same surface spot permits the segregation of the volume and the surface
      contributions from an analyte, while the absence of metal damping permits an
      increase in the propagation length of the optical surface waves and the
      sensitivity of the biosensor. Our technique was tested with the binding of biotin
      molecules to a streptavidin monolayer that has been detected with signal/noise
      ratio of approximately 15 at 1-s signal accumulation time. The detection limit is
      approximately 20 fg of the analyte on the probed spot of the surface.

PMID- 17497830
TI  - 2-Hydroxy-2'-deoxyadenosine 5'-triphosphate enhances A.T --> C.G mutations caused
      by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate by suppressing its degradation
      upon replication in a HeLa extract.
AB  - The coexistence effects of multiple kinds of oxidized deoxyribonucleotides were
      examined using an SV40 origin-dependent in vitro replication system with a HeLa
      extract. Oxidized dGTP and dATP, 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8
      OH-dGTP) and 2-hydroxy-2'-deoxyadenosine 5'-triphosphate (2-OH-dATP), were used
      in this study. The mutation frequency synergistically increased when the two
      oxidized deoxyribonucleotides were together in the reaction. 2-OH-dATP enhanced
      the mutagenicity of 8-OH-dGTP, since the induced mutations were A.T --> C.G
      transversions. The contribution of the highly error-prone DNA polymerase eta was
      unlikely, since similar results were observed with an XP-V cell extract. The
      possible involvement of 2-hydroxyadenine in the complementary (template) strand
      was excluded on the basis of experiments using plasmids containing 2
      hydroxyadenine as templates in the reactions with 8-OH-dGTP. 2-OH-dATP suppressed
      hydrolysis of 8-OH-dGTP, suggesting that the inhibition of the MTH1 protein
      played the major role in the enhancement. These results highlight the importance
      of specific hydrolysis of 8-OH-dGTP for the suppression of its induced mutation.

PMID- 17497832
TI  - Isotopic replacement of pigments and a lipid in chlorosomes from Chlorobium
      limicola: characterization of the resultant chlorosomes.
AB  - Pigments including bacteriochlorophyll (BChl) c, carotenoids, and a trace of BChl
      a together with a lipid, monogalactosyl diglyceride (MGDG), were extracted with
      chloroform/methanol (1:1 v/v) from an aqueous suspension (50 mM Tris-HCl, pH 8.0)
      of chlorosomes from Chlorobium limicola; other lipids and proteins were left
      behind in the aqueous layer by funnel separation. The chloroform layer was dried
      by purging N2 gas, dissolved in methanol, and rapidly injected into the aqueous
      layer to reassemble chlorosomes. This technique has been developed to replace one
      half of the inherent 12C-BChl c by 13C-BChl c to identify the intermolecular
      13C...13C magnetic dipole correlation peaks (that are supposed to reduce their
      intensities to one-fourth by reducing the 13C-BChl c concentration into one-half)
      and to determine the structure of BChl c aggregates in the rod elements by means
      of solid-state NMR spectroscopy. The isotopically replaced chlorosomes were
      characterized (1) by sucrose density gradient centrifugation, zeta potential
      measurement, electron microscopy, and dynamic light scattering measurement to
      determine the morphology of chlorosomes, (2) by 13C NMR spectroscopy, electronic
      absorption and circular dichroism spectroscopies, and low-angle X-ray diffraction
      to determine the pigment assembly in the rod elements, and (3) by subpicosecond
      time-resolved absorption spectroscopy to determine the excited-state dynamics in
      the pigment assembly. The results characterized the reassembled chlorosomes to
      have (1) similar but longer morphological structures, (2) almost the same pigment
      assembly in the rod elements, and (3) basically the same excited-state dynamics
      in the pigment assembly.

PMID- 17497831
TI  - Solution structures of a DNA dodecamer duplex with and without a cisplatin 1,2
      d(GG) intrastrand cross-link: comparison with the same DNA duplex containing an
      oxaliplatin 1,2-d(GG) intrastrand cross-link.
AB  - Proteins that discriminate between cisplatin-DNA adducts and oxaliplatin-DNA
      adducts are thought to be responsible for the differences in tumor range,
      toxicity, and mutagenicity of these two important chemotherapeutic agents.
      However, the structural basis for differential protein recognition of these
      adducts has not been determined and could be important for the design of more
      effective platinum anticancer agents. We have determined high-resolution NMR
      structures for cisplatin-GG and undamaged DNA dodecamers in the AGGC sequence
      context and have compared these structures with the oxaliplatin-GG structure in
      the same sequence context determined previously in our laboratory. This
      structural study allows the first direct comparison of cisplatin-GG DNA and
      oxaliplatin-GG DNA solution structures referenced to undamaged DNA in the same
      sequence context. Non-hydrogen atom rmsds of 0.81 and 1.21 were determined for
      the 15 lowest-energy structures for cisplatin-GG DNA and undamaged DNA,
      respectively, indicating good structural convergence. The theoretical NOESY
      spectra obtained by back-calculation from the final average structures showed
      excellent agreement with the experimental data, indicating that the final
      structures are consistent with the NMR data. Several significant conformational
      differences were observed between the cisplatin-GG adduct and the oxaliplatin-GG
      adduct, including buckle at the 5' G6.C19 base pair, opening at the 3' G7.C18
      base pair, twist at the A5G6.T20C19 base pair step, slide, twist, and roll at the
      G6G7.C19C18 base pair step, slide at the G7C8.C18G17 base pair step, G6G7
      dihedral angle, and overall bend angle. We hypothesize that these conformational
      differences may be related to the ability of various DNA repair proteins, DNA
      binding proteins, and DNA polymerases to discriminate between cisplatin-GG and
      oxaliplatin-GG adducts.

PMID- 17497833
TI  - Theoretical study on the ground and excited states of dicyanocarbene (C3N2) and
      its isomers: a low-temperature matrix emission spectrum attributable to 3-cyano
      2H-azirenylidene.
AB  - Ab initio calculations are used to characterize the ground and low lying excited
      electronic states of selected dicyanocarbene (C(3)N(2) or C(CN)2) isomers. Our
      calculated ground state geometries and the corresponding vibrational frequencies
      agree well with available experimental and theoretical data, thereby providing
      the reliability of the predicted quantities. The present calculations are used to
      identify the possible emitting species for some unidentified emission bands
      observed in certain low-temperature matrices. It is found that the 1(3)A' -->
      X(1)A' transition of 3-cyano-2H-azirenylidene, that is, cyclic C(2)N-CN (Figure
      1c) satisfactorily explains all of the observed spectral features of these bands.

PMID- 17497834
TI  - Experimental and theoretical studies of rate coefficients for the reaction
      O(3P)+C2H5OH at high temperatures.
AB  - Rate coefficients of the reaction O(3P)+C2H5OH in the temperature range 782-1410
      K were determined using a diaphragmless shock tube. O atoms were generated by
      photolysis of SO2 at 193 nm with an ArF excimer laser; their concentrations were
      monitored via atomic resonance absorption. Our data in the range 886-1410 K are
      new. Combined with previous measurements at low temperature, rate coefficients
      determined for the temperature range 297-1410 K are represented by the following
      equation: k(T)=(2.89+/-0.09)x10(-16)T1.62 exp[-(1210+/-90)/T] cm3 molecule(-1) s(
      1); listed errors represent one standard deviation in fitting. Theoretical
      calculations at the CCSD(T)/6-311+G(3df, 2p)//B3LYP/6-311+G(3df) level predict
      potential energies of various reaction paths. Rate coefficients are predicted
      with the canonical variational transition state (CVT) theory with the small
      curvature tunneling correction (SCT) method. Reaction paths associated with trans
      and gauche conformations are both identified. Predicted total rate coefficients,
      1.60 x 10(-22)T3.50 exp(16/T) cm3 molecule(-1) s(-1) for the range 300-3000 K,
      agree satisfactorily with experimental observations. The branching ratios of
      three accessible reaction channels forming CH3CHOH+OH (1a), CH2CH2OH+OH (1b), and
      CH3CH2O+OH (1c) are predicted to vary distinctively with temperature. Below 500
      K, reaction 1a is the predominant path; the branching ratios of reactions 1b,c
      become approximately 40% and approximately 11%, respectively, at 2000 K.

PMID- 17497835
TI  - Heterogeneous chemistry of organic acids on soot surfaces.
AB  - We have investigated the heterogeneous interaction between a number of carboxylic
      acids and soot generated from different fuel sources and formation mechanisms. A
      low-pressure fast flow reactor in conjunction with ion drift-chemical ionization
      mass spectrometry detection was employed to study uptake of monocarboxylic
      (benzoic, oleic, and steric) and dicarboxylic (glutaric, maleic, oxalic, and
      phthalic) acids on deposited soot surfaces formed by combustion of methane,
      propane, and kerosene. Most acids exhibited irreversible uptake on the soot
      surfaces and the uptake coefficient was measured in the range of 9 x 10(-4) to 1
      x 10(-1) estimated based on the geometric surface areas. Brunauer, Emmett, and
      Teller surface areas of the deposited soot surfaces were measured and the soot
      bulk and surface chemical compositions were evaluated with Fourier transform
      infrared spectroscopy and attenuated total reflection spectroscopy. Plausible
      uptake mechanisms were discussed on the basis of the measured soot physiochemical
      properties by comparing the mono and dicarboxylic acids.

PMID- 17497836
TI  - Structure and dynamics of phthalocyanine-argonn (n = 1-4) complexes studied in
      helium nanodroplets.
AB  - Van der Waals clusters of phthalocyanine with 1-4 argon atoms formed inside
      superfluid helium nanodroplets have been investigated by recording fluorescence
      excitation spectra as well as emission spectra. The excitation spectra feature a
      multitude of sharp lines when recorded in superfluid helium droplets in contrast
      to the respective spectra measured in a seeded supersonic beam (Cho et al. Chem.
      Phys. Lett. 2000, 326, 65). The pickup technique used for doping of the
      phthalocyanine and the argon into the droplets allows for nondestructive analysis
      of the cluster sizes. Alternation of the pickup sequence gives information on the
      binding site of the argon atoms. The investigation of dispersed emission spectra
      in helium droplets can be used as a special tool for the identification of 0(0)0
      transitions within the variety of sharp lines seen in the excitation spectra.
      Thus, different isomers of the clusters can be distinguished. Moreover, the
      emission spectra reveal information on dynamic processes such as vibrational
      predissociation of the van der Waals complexes and interconversion among isomeric
      species. The binding energy of the phthalocyanine-argon1 complex in helium
      droplets was estimated to be at most 113 cm-1.

PMID- 17497837
TI  - Transportation of sulfur mustard (HD) in alkyd coating.
AB  - The kinetics of absorption, desorption, and degradation of sulfur mustard (HD) in
      alkyd coating was experimentally studied, and a one-dimension mass transfer model
      for the transportation of HD molecule in alkyd coating was established on the
      experimental data. The obtained results indicated that the persistence of HD
      molecule could be greatly increased due to the absorption of HD droplets by alkyd
      coating, and there still occurred the desorption of HD as vapor from coating for
      more than 3 days even after decontamination of HD droplets onto coating. It was
      also experimentally shown that the majority of HD both absorbed and desorbed was
      accomplished at an early stage, less than 10 h, and HD molecule was able to be
      degraded within the alkyd coating probably through the reactions of hydrolysis
      and elimination. The diffusion coefficient and degradation rate constant of HD in
      alkyd coating were determined to be practically around 10(-9) cm2/s and 2.4 x 10(
      5) min(-1), respectively.

PMID- 17497838
TI  - Information-scattering perspective on orbital hybridization.
AB  - Within the communication theory of the chemical bond, the transformation of
      atomic orbitals (AO) into molecular orbitals (MO) generates the information
      system for the associated electronic promotion of AOs in a molecule. It consists
      of the two orbital-mixing stages involving AOs and MOs, and one MO-occupation
      subchannel. The conditional-entropy and mutual-information descriptors of this
      resultant "communication" system, which measure the average "noise" and the
      amount of information in the molecular channel, provide novel information
      theoretic measures of the system bond covalency and ionicity, respectively. This
      information-theoretic approach to the many-center probability-scattering in AO
      resolution is now applied to the one-center orbital transformations to examine
      the entropic indices of an effective promotion of the canonical AO in alternative
      valence states of an atom, identified by different occupations of hybrid orbitals
      (HO). This phenomenon is first illustrated and tested using the simplest scheme
      of mixing two atomic orbitals in a generalized sp hybridization. The conditions
      for the maximum of the AO-promotion covalency are examined, and the shape
      independence of the orbital channels and their entropy/information descriptors
      for the equalized probability weights of HO in the specified atomic valence state
      is commented upon. Entropic indices are then generated for selected valence
      states of the carbon atom, resulting from different hybridization schemes, in
      order to characterize their complementary aspects of the system electron
      polarization (one-center ionicity) and electron delocalization (one-center
      covalency). The interpretation of these components as measures of a degree of the
      acquired "order" and surviving "disorder" (electron uncertainty) in the valence
      state is also given. These results are found to generally agree with intuitive
      expectations. The exact HO-occupation subchannel is derived, which reproduces the
      average AO occupations in the valence state. This approach is also proposed for
      the multicenter probability scattering in molecules, via the system occupied MO,
      in probing the system chemical bonds.

PMID- 17497840
TI  - Investigation into the P3 binding domain of m-calpain using photoswitchable diazo
      and triazene-dipeptide aldehydes: new anticataract agents.
AB  - The photoswitchable N-terminal diazo and triazene-dipeptide aldehydes 8a-d,
      10a,b, and 17a,b present predominantly as the (E)-isomer, which purportedly binds
      deep in the S3 pocket of calpain. All compounds are potent inhibitors of m
      calpain, with 8b being the most active (IC50 of 35 nM). The diazo-containing
      inhibitors 8a, 8c, and 10a were irradiated at 340 nm to give a photostationary
      state enriched in the (Z)-isomer, and in all cases, these were less active. The
      most water soluble triazene 17a (IC50 of 90 nM) retards calpain-induced cataract
      formation in lens culture.

PMID- 17497839
TI  - Bifunctional [2',6'-dimethyl-L-tyrosine1]endomorphin-2 analogues substituted at
      position 3 with alkylated phenylalanine derivatives yield potent mixed mu
      agonist/delta-antagonist and dual mu-agonist/delta-agonist opioid ligands.
AB  - Endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2) and [Dmt1]EM-2 (Dmt = 2',6'-dimethyl-l
      tyrosine) analogues, containing alkylated Phe3 derivatives, 2'-monomethyl (2,
      2'), 3',5'- and 2',6'-dimethyl (3, 3', and 4', respectively), 2',4',6'-trimethyl
      (6, 6'), 2'-ethyl-6'-methyl (7, 7'), and 2'-isopropyl-6'-methyl (8, 8') groups or
      Dmt (5, 5'), had the following characteristics: (i) [Xaa3]EM-2 analogues
      exhibited improved mu- and delta-opioid receptor affinities. The latter, however,
      were inconsequential (Kidelta = 491-3451 nM). (ii) [Dmt1,Xaa3]EM-2 analogues
      enhanced mu- and delta-opioid receptor affinities (Kimu = 0.069-0.32 nM; Kidelta
      = 1.83-99.8 nM) without kappa-opioid receptor interaction. (iii) There were
      elevated mu-bioactivity (IC50 = 0.12-14.4 nM) and abolished delta-agonism (IC50 >
      10 muM in 2', 3', 4', 5', 6'), although 4' and 6' demonstrated a potent mixed mu
      agonism/delta-antagonism (for 4', IC50mu = 0.12 and pA2 = 8.15; for 6', IC50mu =
      0.21 nM and pA2 = 9.05) and 7' was a dual mu-agonist/delta-agonist (IC50mu = 0.17
      nM; IC50delta = 0.51 nM).

PMID- 17497841
TI  - Arylthioindole inhibitors of tubulin polymerization. 3. Biological evaluation,
      structure-activity relationships and molecular modeling studies.
AB  - The new arylthioindole (ATI) derivatives 10, 14-18, and 21-24, which bear a
      halogen atom or a small size ether group at position 5 of the indole moiety, were
      compared with the reference compounds colchicine and combretastatin A-4 for
      biological activity. Derivatives 10, 11, 16, and 21-24 inhibited MCF-7 cell
      growth with IC50 values <50 nM. A halogen atom (14-17) at position 5 caused a
      significant reduction in the free energy of binding of compound to tubulin, with
      a concomitant reduction in cytotoxicity. In contrast, methyl (21) and methoxy
      (22) substituents at position 5 caused an increase in cytotoxicity. Compound 16,
      the most potent antitubulin agent, led to a large increase (56%) in HeLa cells in
      the G2/M phase at 24 h, and at 48 h, 26% of the cells were hyperploid. Molecular
      modeling studies showed that, despite the absence of the ester moiety present in
      the previously examined analogues, most of the compounds bind in the colchicine
      site in the same orientation as the previously studied ATIs. Binding to beta
      tubulin involved formation of a hydrogen bond between the indole and Thr179 and
      positioning of the trimethoxy phenyl group in a hydrophobic pocket near Cys241.

PMID- 17497842
TI  - Exploring the structure-activity relationship of the ethylamine portion of 3
      iodothyronamine for rat and mouse trace amine-associated receptor 1.
AB  - 3-iodothyronamine (1, T1AM) is a naturally occurring derivative of thyroid
      hormone that can potently activate the orphan G protein-coupled receptor (GPCR)
      known as the trace amine-associated receptor 1 (TAAR1). We have previously found
      that modifying the outer ring of the phenoxyphenethylamine core scaffold of 1 can
      improve potency and provide potent agonists. In this study, we explored the
      tolerance of rat and mouse TAAR1 (rTAAR1 and mTAAR1) for structural modifications
      in the ethylamine portion of 1. We found that incorporating unsaturated
      hydrocarbon substituents and polar, hydrogen-bond-accepting groups were
      beneficial for rTAAR1 and mTAAR1, respectively, providing compounds that were
      equipotent or more potent than 1. Additionally, we have discovered that a
      naphthyl group is an excellent isosteric replacement for the iodophenyl ring of
      1.

PMID- 17497844
TI  - QUASI: a novel method for simultaneous superposition of multiple flexible ligands
      and virtual screening using partial similarity.
AB  - The structure of many receptors is unknown, and only information about diverse
      ligands binding to them is available. A new method is presented for the
      superposition of such ligands, derivation of putative receptor site models and
      utilization of the models for screening of compound databases. In order to
      generate a receptor model, the similarity of all ligands is optimized
      simultaneously taking into account conformational flexibility and also the
      possibility that the ligands can bind to different regions of the site and only
      partially overlap. Ligand similarity is defined with respect to a receptor site
      model serving as a common reference frame. The receptor model is dynamic and
      coevolves with the ligand alignment until an optimal self-consistent
      superposition is achieved. When ligand conformational flexibility is permitted,
      different superposition models are possible and consistent with the data.
      Clustering of the superposition solutions is used to obtain diverse models. When
      the models are used to screen a database of compounds, high enrichments are
      obtained, comparable to those obtained in docking studies.

PMID- 17497845
TI  - QSPR study of critical micelle concentration of anionic surfactants using
      computational molecular descriptors.
AB  - A data set of 181 diverse anionic surfactants has been investigated to relate the
      logarithm of critical micelle concentration (cmc) to the molecular structure
      using Comprehensive Descriptors for Structural and Statistical Analysis (CODESSA
      Pro) software. A fragment approach provided superior quantitative structure
      property relationship (QSPR) models in terms of statistical characteristics and
      predictive ability. The regression equations provided insight into the structural
      features of surfactants that influence cmc. The most obvious influence on cmc was
      manifested by hydrophobic fragments expressed by the topological and geometrical
      descriptors, while the hydrophilic fragment is represented by constitutional,
      geometrical, and charge related descriptors. Significantly important molecular
      descriptors in the selected QSPR models were topological, solvational, and charge
      related descriptors as the driving force of the intermolecular interactions
      between anionic surfactants and water.

PMID- 17497846
TI  - Electrospray ionization mass spectrometry of a novel family of complexes in which
      various nitroso compounds are stabilized via coordination to [IrCl5]2-.
AB  - Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry
      (ESI-MS/MS) data of a unique family of complexes of nitroso compounds coordinated
      to pentachloroiridate(III), [Cl5IrN(O)XR]2- (X=NH, S, CH and R=alkyl, aryl) are
      presented. These novel complexes are obtained by nucleophilic attack of primary
      amines, thiols. and alkenes to the coordinated nitrosyl. Despite their lability
      and low volatility, MS analysis of complexes of the type MN(O)X was done for the
      first time, complementing other spectroscopic techniques. The intrinsic
      dissociation chemistry of the gaseous diagnostic ions was studied via ESI-MS/MS
      and found to be very useful to confirm the proposed connectivities of the parent
      complexes. In particular, ESI-MS of their solutions allows the detection of
      series of diagnostic ions, mainly, [M-Cl]-, [M+K]-, [M-NO]-*, and [M-Cl+AcN]-
      (AcN=acetonitrile), which confirmed the identity of the analyzed complexes to be
      M=[Cl5IrN(O)XR]2-. Major fragments were formed by losses of NO or N(O)XR. ESI-MS
      and ESI-MS/MS measurements are therefore shown to be the proper techniques to
      complement the spectroscopic characterization of this important class of nitroso
      complexes. An interesting rearrangement that does not take place in solution was
      observed in the gaseous phase, and a plausible mechanism is discussed.

PMID- 17497847
TI  - Theoretical investigation of the first-shell mechanism of nitrile hydratase.
AB  - The first-shell mechanism of nitrile hydratase (NHase) is investigated
      theoretically using density functional theory. NHases catalyze the conversion of
      nitriles to amides and are classified into two groups, the non-heme Fe(III)
      NHases and the non-corrinoid Co(III) NHases. The active site of the non-heme iron
      NHase comprises a low-spin iron (S=1/2) with a remarkable set of ligands,
      including two deprotonated backbone nitrogens and both cysteine-sulfenic and
      cysteine-sulfinic acids. A widely proposed reaction mechanism of NHase is the
      first-shell mechanism in which the nitrile substrate binds directly to the low
      spin iron in the sixth coordination site. We have used quantum chemical models of
      the NHase active site to investigate this mechanism. We present potential energy
      profiles for the reaction and provide characterization of the intermediates and
      transition-state structures for the NHase-mediated conversion of acetonitrile.
      The results indicate that the first-shell ligand Cys114-SO- could be a possible
      base in the nitrile hydration mechanism, abstracting a proton from the
      nucleophilic water molecule. The generally suggested role of the Fe(III) center
      as a Lewis acid, activating the substrate toward nucleophilic attack, is shown to
      be unlikely. Instead, the metal is suggested to provide electrostatic
      stabilization to the anionic imidate intermediate, thereby lowering the reaction
      barrier.

PMID- 17497848
TI  - Dual triggering of DNA binding and fluorescence via photoactivation of a
      dinuclear ruthenium(II) arene complex.
AB  - The dinuclear RuII arene complexes [{(eta6-arene)RuCl}2(mu-2,3-dpp)](PF6)2,
      arene=indan (1), benzene (2), p-cymene (3), or hexamethylbenzene (4) and 2,3
      dpp=2,3-bis(2-pyridyl)pyrazine, have been synthesized and characterized. Upon
      irradiation with UVA light, complexes 1 and 2 readily underwent arene loss, while
      complexes 3 and 4 did not. The photochemistry of 1 was studied in detail. In the
      X-ray structure of [{(eta6-indan)RuCl}2(mu-2,3-dpp)](PF6)2 (1), 2,3-dpp bridges
      two RuII centers 6.8529(6) A apart. In water, aquation of 1 in the dark occurs
      with replacement of chloride with biexponential kinetics and decay constants of
      100+/-1 min-1 and 580+/-11 min-1. This aquation was suppressed by 0.1 M NaCl. UV
      or visible irradiation of 1 in aqueous or methanolic solution led to arene loss.
      The fluorescence of the unbound arene is approximately 40 times greater than when
      it is complexed. Irradiation of 1 also had a significant effect on its
      interactions with DNA. The DNA binding of 1 is increased after irradiation. The
      non-irradiated form of 1 preferentially formed DNA adducts that only weakly
      blocked RNA polymerase, while irradiation of 1 transformed the adducts into
      stronger blocks for RNA polymerase. The efficiency of irradiated 1 to form DNA
      interstrand cross-links was slightly greater than that of cisplatin in both 10 mM
      NaClO4 and 0.1 M NaCl. In contrast, the interstrand cross-linking efficiency of
      non-irradiated 1 in 10 mM NaClO4 was relatively low. An intermediate amount of
      cross-linking was observed when the sample of DNA already modified by non
      irradiated 1 was irradiated. DNA unwinding measurements supported the conclusion
      that both mono- and bifunctional adducts with DNA can form. These results show
      that photoactivation of dinuclear RuII arene complexes can simultaneously produce
      a highly reactive ruthenium species that can bind to DNA and a fluorescent marker
      (the free arene). Importantly, the mechanism of photoreactivity is also
      independent of oxygen. These complexes, therefore, have the potential to combine
      both photoinduced cell death and fluorescence imaging of the location and
      efficiency of the photoactivation process.

PMID- 17497849
TI  - Hydrothermal and structural chemistry of the zinc(II)- and cadmium(II)-1,2,4
      triazolate systems.
AB  - Hydrothermal reactions of 1,2,4-triazole with zinc and cadmium salts have yielded
      10 structurally unique materials of the M(II)/trz/Xn- system, with M(II)=Zn and
      Cd and Xn-=F-, Cl-, Br-, I-, OH-, NO3-, and SO(4)2- (trz=1,2,4-triazolate). Of
      the zinc-containing phases, [Zn(trz)2] (1), [Zn2(trz)3(OH)].3H2O (3.3H2O), and
      [Zn2(trz)(SO4)(OH)] (4) are three-dimensional, while [Zn(trz)Br] (2) is two
      dimensional. All six cadmium phases, [Cd3(trz)3F2(H2O)].2.75H2O (5.2.75H2O),
      [Cd2(trz)2Cl2(H2O)] (6), [Cd3(trz)3Br3] (7), [Cd2(trz)3I] (8),
      [Cd3(trz)5(NO3)(H2O)].H2O (9.H2O), and [Cd8(trz)4(OH)2(SO4)5(H2O)] (10), are
      three-dimensional. In all cases, the anionic components Xn- participate in the
      framework connectivity as bridging ligands. The structural diversity of these
      materials is reflected in the variety of coordination polyhedra displayed by the
      metal sites: tetrahedral; trigonal bipyramidal; octahedral. Structures 3, 5, and
      7-9 exhibit two distinct polyhedral building blocks. The materials are also
      characterized by a range of substructural components, including trinuclear and
      tetranuclear clusters, adamantoid cages, chains, layers, and complex frameworks.

PMID- 17497850
TI  - Compositional effects in Ru, Pd, Pt, and Rh-doped mesoporous tantalum oxide
      catalysts for ammonia synthesis.
AB  - A series of early metal-promoted Ru-, Pd-, Pt-, and Rh-doped mesoporous tantalum
      oxide catalysts were synthesized using a variety of dopant ratios and dopant
      precursors, and the effects of these parameters on the catalytic activity of NH3
      synthesis from H2 and N2 were explored. Previous studies on this system supported
      an unprecedented mechanism in which N-N cleavage occurred at the Ta sites rather
      than on Ru. The results of the present study showed, for all systems, that Ba is
      a better promoter than Cs or La and that the nitrate is a superior precursor for
      Ba than the isopropoxide or the hydroxide. 15N-labeling studies showed that
      residual nitrate functions as the major ammonia source in the first hour but that
      it does not account for the ammonia produced after the nitrate is completely
      consumed. Ru3(CO)12 proved to be a better Ru precursor than RuCl(3).3H2O, and an
      almost linear increase in activity with increasing Ru loading level was observed
      at 350 degrees C (623 K). However, at 175 degrees C (448 K), the increase in Ru
      had no effect on the reaction rate. Pd functioned with comparable rates to Ru,
      while Pt and Rh functioned far less efficiently. The surprising activities for
      the Pd-doped catalysts, coupled with XPS evidence for low-valent Ta in this
      catalyst system, support a mechanism in which cleavage of the N-N triple bond
      occurs on Ta rather than the precious metal because the Ea value for N-N cleavage
      on Pd is 2.5 times greater than that for Ru, and the 9.3 kJ mol-1 Ea value
      measured previously for the Ru system suggests that N-N cleavage cannot occur at
      the Ru surface.

PMID- 17497851
TI  - Controlled copper-mediated chlorination of phenol rings under mild conditions.
AB  - The very unusual case of copper-mediated chlorination of phenol rings under mild
      conditions at room temperature is reported. Reaction of the ligand 1,7-bis(2
      hydroxyphenyl)-2,6-diaza-4-hydroxylheptane (H3L1) with CuCl2 in acetonitrile
      leads to either the formation of a tetranuclear copper(II) complex [Cu4(HL3)2(mu
      Cl)2Cl2](CH3CN) (1) or a linear trinuclear complex [Cu3(HL1)2Cl2(CH3CN)2](CH3CN)2
      (2), depending on the reaction conditions. Both compounds have been fully
      characterized, including the determination of their 3D structures by X-ray
      diffraction. The unprecedented tetranuclear compound 1 is constituted of a
      dichlorido-bridged dimer of di-mu-phenoxido-dinuclear species, whereas the
      trinuclear complex 2 presents a linear array of copper(II) ions, held together
      through di-mu-phenoxido bridges of the central and external ions. The magnetic
      susceptibility of the two compounds was investigated, revealing either very
      strong (J<-500 cm-1) or strong (J value around -370(1) cm-1) antiferromagnetic
      dominant interactions among the CuII ions for 1 and 2, respectively. The
      tetranuclear complex 1 is obtained, under dry conditions, through the in situ
      formation of ligand HL3 (H3L3=1,7-bis(2-hydroxy-5-chlorophenyl)-2,6-diaza-4
      hydroxylheptane) by oxidative chlorination of (HL1)2-. In the presence of traces
      of water, 1 is partially hydroxylated at the ortho position of one of the phenyl
      rings. The use of trimethylorthoformate as the dehydrating agent prevents the
      formation of hydroxylated ligands. Several partly chlorinated/hydroxylated
      products (identified as H3L2) have also been obtained through slight variations
      of the synthetic procedures (presence or absence of water and/or triethylamine in
      the reaction mixtures). These partially chlorinated and/or hydroxylated
      coordination species are mutually isomorphous to either 1 or 2. Several
      "modified" ligands have been isolated and characterized by 1H NMR and MS, after
      reaction with sodium sulfide of the complexes formed.

PMID- 17497852
TI  - Synthesis, characterization, and optical properties of In2O3 semiconductor
      nanowires.
AB  - In2O3 semiconductor nanowires were synthesized by the chemical vapor deposition
      method through carbon thermal reduction at 900 degrees C with 95% Ar and 5% O2
      gas flow. The In2O3 nanowires were characterized by field emission scanning
      electron microscopy (FE-SEM), high-resolution transmission electron microscopy
      (HRTEM), and photoluminescence spectroscopy (PL). For the first time, we observed
      the formation of corundum-type h-In2O3 nanowires and branched In2O3 nanowires.
      The PL spectra of In2O3 nanowires show strong visible red emission at 1.85 eV
      (670 nm) at low temperature, possibly caused by a small amount of oxygen
      vacancies in the nanowire crystal structure.

PMID- 17497853
TI  - Osmium NAMI-A analogues: synthesis, structural and spectroscopic
      characterization, and antiproliferative properties.
AB  - The osmium(III) complex [(DMSO)2H][trans-OsIIICl4(DMSO)2] (1) has been prepared
      via stepwise reduction of OsO4 in concentrated HCl using N2H(4).2HCl and
      SnCl(2).2H2O in DMSO. 1 reacts with a number of azole ligands, namely, indazole
      (Hind), pyrazole (Hpz), benzimidazole (Hbzim), imidazole (Him), and 1H-1,2,4
      triazole (Htrz), in organic solvents, affording novel complexes
      (H2ind)[OsIIICl4(Hind)(DMSO)] (2), (H2pz)[OsIIICl4(Hpz)(DMSO)] (3),
      (H2bzim)[OsIIICl4(Hbzim)(DMSO)] (4), (H2im)[OsIIICl4(Him)(DMSO)] (6), and
      (H2trz)[OsIIICl4(Htrz)(DMSO)] (7), which are close analogues of the
      antimetastatic complex NAMI-A. Metathesis reaction of 4 with
      benzyltriphenylphosphonium chloride in methanol led to the formation of
      (Ph3PCH2Ph)[OsIIICl4(Hbzim)(DMSO)] (5). The complexes were characterized by IR,
      UV-vis, ESI mass spectrometry, 1H NMR spectroscopy, cyclic voltammetry, and X-ray
      crystallography. In contrast to NAMI-A, 2-4, 6, and 7 are kinetically stable in
      aqueous solution and resistant to hydrolysis. Surprisingly, they show reasonable
      antiproliferative activity in vitro in two human cell lines, HT-29 (colon
      carcinoma) and SK-BR-3 (mammary carcinoma), when compared with analogous
      ruthenium compounds. Structure-activity relationships and the potential of the
      prepared complexes for further development are discussed.

PMID- 17497854
TI  - Nitroxide/substrate weak hydrogen bonding: attitude and dynamics of collisions in
      solution.
AB  - The study of intermolecular collisions and bonding interactions in solutions is
      of critical importance in understanding and predicting solute/solvent properties.
      Previous work has established that stable paramagnetic nitroxide molecules are
      excellent probes of intermolecular interactions for hydrogen bonding in polar
      solvents. In this study, 1H, 2H, 13C, 15N NMR and liquid/liquid intermolecular
      transfer dynamic nuclear polarization (L2IT DNP) results are obtained for the
      paramagnetic probe molecule, TEMPO, interacting with the common aprotic and
      protic polar solvents, CH3CN and CH3CONH2, yielding a profile of both dipolar and
      scalar interactions. A significant scalar contact hyperfine is observed for the N
      O...H-C interaction (13CH3 hyperfine, a/h=0.66 MHz) in the CH3CN/TEMPO system,
      whereas the N-O...H-C and N-O...H-N interactions for the TEMPO/CH3CONH2 system
      yield 13CH3 and 15N hyperfine couplings of a/h=0.16 and -0.50 MHz, respectively.
      The distance and attitude of the scalar interaction for the nitroxide hydrogen
      bonding at the methyl group in CH3CN and the amino group in CH3CONH2 are computed
      using density functional theory (DFT), yielding good agreement with the
      experimental results. These results show that the hyperfine coupling provides a
      sensitive probe of weak hydrogen-bonding interactions in solution.

PMID- 17497855
TI  - Solvent control of charge localization in 11-bond bridged dinitroaromatic radical
      anions.
AB  - The optical spectra of 4,4'-dinitrostilbene (1-) and 4,4'-dinitrotolane (2-)
      radical anions show the narrow band widths and partially resolved vibrational
      structure exhibited by charge-delocalized dinitroaromatic radical anions in the
      solvents THF, HMPA, and DMPU (dimethylpropyleneurea). Both show the broad, nearly
      Gaussian-shaped bands found for charge-localized intervalence compounds in DMF,
      DMSO, and MeCN, with the transition energy of the band maximum, which equals the
      vertical reorganization energy (lambda) for localized intervalence compounds,
      increasing in that order. In contrast, 4,4'-dinitroazobenzene (3-) remains
      delocalized in these solvents, although the line width required to simulate the
      vibrational structure increases by 200 cm-1 in DMF and 400 cm-1 in MeCN compared
      to HMPA. The change from localized to delocalized spectra as a function of
      solvent establishes the transition energy for which delocalization occurs and
      demonstrates that, as predicted, the Hush method substantially underestimates the
      electronic coupling for compounds that lie near the borderline.

PMID- 17497856
TI  - Probing excitation delocalization in supramolecular chiral stacks by means of
      circularly polarized light: experiment and modeling.
AB  - Photoexcitations in helical aggregates of a functionalized, chiral
      oligophenylenevinylene (MOPV) are described going beyond the Born-Oppenheimer
      approximation, in the form of dressed (polaronic) Frenkel excitons. This allows
      for accurate modeling of the experimentally observed wavelength dependence of the
      circular polarization in fluorescence, which directly probes the non-adiabatic
      nature of the electron-vibration (EV) coupling in this system. The fluorescence
      photon is emitted from a nuclear geometry in which one MOPV and its two nearest
      neighbors have a nuclear equilibrium that differs appreciably from the ground
      state due to the presence of the excited state. The absorption and emission band
      shape and the circular dichroism are consistent with a coherence range of the
      emitting excitation of approximately two neighboring molecules. Random
      fluctuations in the zero-order excited-state energy of the MOPVs (disorder) limit
      the exciton delocalization and can be described by a Gaussian distribution of
      energies with a width sigma=0.12 eV and a spatial correlation length l0
      approximately 5 molecules. We find that disorder and EV coupling act
      synergistically in localizing the emitting exciton to a single MOPV in the
      aggregate with 95% probability.

PMID- 17497857
TI  - Transition state analysis of acid-catalyzed dAMP hydrolysis.
AB  - Multiple kinetic isotope effects (KIEs) on deoxyadenosine monophosphate (dAMP)
      hydrolysis in 0.1 M HCl were used to determine the transition state (TS)
      structure and probe its intrinsic reactivity. The experimental KIEs revealed a
      stepwise (SN1) mechanism, with a discrete oxacarbenium ion intermediate. This is
      the first direct evidence for the deoxyribosyl oxacarbenium ion in solution. In
      50% methanol/0.1 M HCl the products were deoxyribose 5-phosphate (dRMP) and alpha
      and beta-methyl dRMP. The alpha-Me-dRMP/beta-Me-dRMP ratio was 8.5:1. Assuming
      that a free oxacarbenium ion is equally susceptible to nucleophilic attack on
      either face, this indicated that approximately 20% proceeded through a solvent
      separated ion pair complex, or free oxacarbenium ion, a DN+AN mechanism, while
      approximately 80% of the reaction proceeded through a contact ion pair complex.
      The oxacarbenium ion lifetime was estimated at 10(-11)-10(-10) s. Computational
      transition states were found for ANDN, DN*AN, DN*AN, and DN+AN mechanisms using
      hybrid density functional theory calculations. After taking into account 20% of
      DN+AN, there was an excellent match of calculated to experimental KIEs for 80% of
      the reaction having a DN*AN mechanism. That is, C-N bond cleavage is reversible,
      with dAMP and the {oxacarbenium ion*adenine} complex in equilibrium. The first
      irreversible step is water attack on the oxacarbenium ion. The calculated 1'-14C
      KIE for a stepwise mechanism with irreversible C-N bond cleavage (DN*AN) was
      1.052, in the range previously associated only with ANDN transition states, and
      close to the calculated ANDN value, 1.059. The 1'-14C KIE was strongly dependent
      on the adenine protonation state.

PMID- 17497858
TI  - Excited-state quenching by proton-coupled electron transfer.

PMID- 17497859
TI  - trans-W(Cmesityl)(dmpe)2H: revealing a highly polar W-H bond and H-mobility in
      liquid and solid state.
AB  - The isotopomeric complexes trans-W(Cmesityl)[(C(H,D)3)2PCH2CH2P(C(H,D)3)2]2(H,D)
      1-4 were prepared. 2 (W(Cmesityl)(dmpe)2D) was used to study the Deuterium
      Quadrupole Coupling Constant (DQCC) and the ionicity of the W-D bond (DQCC=34.1
      kHz; ionicity 85%). 1 (W(Cmesityl)(dmpe)2H) shows several dynamic exchange
      processes in solution, such as HW/HW, HW/ortho-Memesityl, and HW/H2 exchanges
      observed by NMR in combination with deuterium labeling studies and double label
      crossover experiments. Except for the HW/H2, these reactions comprise elementary
      steps, which also appear along the isomerization pathway of 1 into (2,3,5
      trimethylphenylcarbyne)(dmpe)2WH (5) at 60 degrees C. 5 was characterized by an X
      ray diffraction study. In the solid state only an HW/Mep exchange process
      prevails appearing at higher temperatures, which was identified by NMR and by
      Quasielastic Neutron Scattering. The latter also provided an activation barrier
      of 5 kcal/mol and a "jump width" for the moving H nucleus in agreement with the
      HW...Mep distance of the X-ray diffraction study of 1.

PMID- 17497860
TI  - Direct access to N-H-aziridines from asymmetric catalytic aziridination with
      borate catalysts derived from vaulted binaphthol and vaulted biphenanthrol
      ligands.
AB  - The asymmetric catalytic aziridination reaction (AZ reaction) of N
      dianisylmethylimines (N-DAM-imines) with ethyl diazoacetate is developed with
      chiral catalysts prepared from triphenylborate and both the vaulted binaphthol
      (VANOL) and vaulted biphenanthrol (VAPOL) ligands. Catalysts derived from both
      ligands were equally effective in terms of asymmetric induction, but the VANOL
      catalyst was slightly faster. Up to 400 turnovers could be achieved with the
      VANOL catalyst while still maintaining>or=90% ee in the aziridine product. The
      ligand could be recovered in 95% yield with no loss in optical purity. Excellent
      asymmetric inductions were observed with arylimines, and although slightly lower
      inductions were observed for alkyl-substituted imines, the optical purity of the
      aziridines from all of the imine substrates could be enhanced to>or=99% ee with a
      single crystallization. Methods were developed for deprotection of the N-DAM
      aziridines under acidic conditions without causing an acid-promoted opening of
      the ring. Excellent yields of the N-H-aziridines could be obtained with both
      alkyl- and aryl-substituted aziridines. Finally, activation of the N-H-aziridines
      was achieved with Boc, tosyl, and Fmoc groups. The activated aziridines can be
      converted to beta3-amino esters, and unexpectedly, the N-Boc-protected aziridine
      2-carboxylate 16b with a phenyl substituent in the 3-position cis to the ester
      group was found to undergo ring expansion to a mixture of cis- and trans
      oxazolidinones.

PMID- 17497861
TI  - Photoinduced conformational switch of enantiopure azobenzenes controlled by a
      sulfoxide.
AB  - Two series of enantiopure azobenzenes with a p-tolylsulfoxide at the ortho or
      meta position with respect to the azo group, have been regioselectively
      synthesized. Both can act as enantiopure molecular switches showing different
      structural features owing to the presence of the stereogenic sulfur. The
      photoisomerization process, studied by UV-vis, circular dichroism (CD), NMR, and
      chiral HPLC evidenced a double role of the sulfoxide. A transfer of chirality
      from the sulfoxide to the azo system was observed by CD in both cis and trans
      isomers of the meta sulfinyl derivatives 3, whereas this perturbation was evident
      for the ortho sulfinyl series 7 only in the cis isomer. The NMR study evidenced
      that the s-cis rigid conformation of the bisaromatic sulfoxide was fixing a
      different orientation of the overall system in each series both in the trans and
      cis isomers, by forcing a final U-shaped structure in cis-3 and an S-shaped
      structure in cis-7. Very different values of specific optical rotations were
      measured in both trans and cis isomers, also reflecting the existence of distinct
      chiral entities in the photostationary states. The easy and reversible changes
      occurring between different conformational states could find applications in the
      photocontrol of several molecular switches.

PMID- 17497862
TI  - Double-lanthanide-binding tags: design, photophysical properties, and NMR
      applications.
AB  - Lanthanide-binding tags (LBTs) are peptide sequences of up to 20 encoded amino
      acids that tightly and selectively complex lanthanide ions and can sensitize
      terbium (Tb3+) luminescence. On the basis of these properties, it was predicted
      that increasing the number of bound lanthanides would improve the capabilities of
      these tags. Therefore, using a structurally well-characterized single-LBT
      sequence as a starting point, a "double-LBT" (dLBT), which concatenates two
      lanthanide-binding motifs, was designed. Herein we report the generation of dLBT
      peptides and luminescence and NMR studies on a dLBT-tagged ubiquitin fusion
      protein. These lanthanide-bound constructs are shown to be improved luminescent
      tags with avid lanthanide binding and up to 3-fold greater luminescence
      intensity. NMR experiments were conducted on the ubiquitin construct, wherein
      bound paramagnetic lanthanides were used as alignment-inducing agents to gain
      residual dipolar couplings, which are valuable restraints for macromolecular
      structure determination. Together, these results indicate that dLBTs will be
      valuable chemical tools for biophysical applications leading to new approaches
      for studying the structure, function, and dynamics of proteins.

PMID- 17497863
TI  - Double-lanthanide-binding tags for macromolecular crystallographic structure
      determination.
AB  - A double-lanthanide-binding tag (dLBT), a small peptide sequence engineered to
      bind two lanthanide ions (e.g., Tb3+) with high affinity, was used to solve the
      phase problem for the structure determination of ubiquitin by the single
      wavelength anomalous diffraction (SAD) method. Since the dLBT is comprised
      exclusively of encoded amino acids, the necessity for the incorporation of
      unnatural amino acids or chemical modification of the protein as a prerequisite
      for X-ray structure determination is eliminated. A construct encoding the dLBT as
      an N-terminal fusion with ubiquitin provides for facile expression and
      purification using standard methods. Phasing of the single-wavelength X-ray data
      (at 2.6 A resolution) using only the anomalous signal from the two tightly bound
      Tb3+ ions in the dLBT led to clear electron-density maps. Nearly 75% of the
      ubiquitin structure was built using automated model-building software without
      user intervention. It is anticipated that this technique will be broadly
      applicable, complementing existing macromolecular phasing methodologies. The dLBT
      should be particularly useful in cases where protein derivatization with heavy
      atoms proves to be problematic or synchrotron facilities are unavailable.

PMID- 17497864
TI  - Synthesis and stabilization of FeCo nanoparticles.

PMID- 17497865
TI  - Synthesis and characterization of the Keggin-type ruthenium-nitrido derivative
      [PW11O39{RuN}]4- and evidence of its electrophilic reactivity.
AB  - The ruthenium-nitrido POM derivative [PW11O39{RuVIN}]4- has been synthesized by
      reaction between [PW11O39]7- and [RuVINCl5]2- or [RuVINCl4]-. Its molecular
      structure has been confirmed from multinuclear 31P and 183W NMR spectroscopy
      together with an EXAFS study, while the oxidation state of the ruthenium bearing
      the nitrido ligand has been inferred both from 183W NMR and XANES analysis at the
      Ru-K edge. The potential of [PW11O39{RuVIN}]4- in N-atom transfer reactions has
      been demonstrated through reaction with triphenylphosphine, which ultimately
      leads to the release of the bis(triphenylphosphane)iminium cation [PPh3=N=PPh3]+
      through several intermediates, among which the phosphoraniminato derivative
      [PW11O39{RuVNPh3}]3- has been structurally characterized. Its unusual oxidation
      state is in accordance with its EPR spectrum.

PMID- 17497866
TI  - Enantioselective organocatalytic singly occupied molecular orbital activation:
      the enantioselective alpha-enolation of aldehydes.

PMID- 17497867
TI  - Synthesis of phosphinopeptides via the Mannich ligation.
AB  - Phosphinopeptides are a class of unnatural peptides containing a tetrahedral
      phosphorus atom and have potential for use as enzyme inhibitors. A series of
      phosphinopeptides were synthesized via the Mannich-type reaction of
      aryldichlorophosphines, aldehydes, and N-protected amino amides or peptide amides
      and subsequent aminolysis with amino esters or peptide esters. The current method
      named the Mannich ligation is an efficient route to synthesis of
      phosphinopeptides through convergent condensation.

PMID- 17497868
TI  - Enantioselective total synthesis of (-)-Salinosporamide A (NPI-0052).
AB  - A novel enantioselective total synthesis of 20S proteasome inhibitor
      Salinosporamide A (NPI-0052; 1) is presented. Key features include intramolecular
      aldol cyclization of 6 to simultaneously generate the three chiral centers of
      advanced intermediate 5, cyclohexene ring addition using B-2-cyclohexen-1-yl-9
      BBN, and inversion of the C-5 stereocenter by oxidation followed by
      enantioselective enzymatic reduction.

PMID- 17497869
TI  - Asymmetric annulation toward pyrrolopiperazinones: concise enantioselective
      syntheses of pyrrole alkaloid natural products.
AB  - A novel Pd-catalyzed asymmetric annulation between 5-bromopyrrole-2-carboxylate
      esters and vinyl aziridines has been developed to efficiently construct
      pyrrolopiperazinones, which can serve as key intermediates in the
      enantioselective syntheses of pyrrole alkaloid natural products. In this paper,
      the total synthesis of (-)-longamide B in five steps and the first total
      syntheses of agesamides A and B in six steps from 6 and 7 are reported.

PMID- 17497870
TI  - Palladium-catalyzed direct arylation of aryl(azaaryl)methanes with aryl halides
      providing triarylmethanes.
AB  - Direct arylation of aryl(azaaryl)methanes with aryl halides takes place at the
      benzylic position in the presence of a hydroxide base under palladium catalysis
      to yield triarylmethanes.

PMID- 17497871
TI  - Synthesis of DEFG ring of complestatin and chloropeptin I: highly
      atropdiastereoselective macrocyclization by intramolecular Suzuki-Miyaura
      reaction.
AB  - Palladium-catalyzed intramolecular Suzuki-Miyaura reaction of linear tripeptide
      (23) afforded the 16-membered DEFG ring of complestatin (3) in good yield with an
      excellent atropdiastereoselectivity. Acidic treatment of 3 triggers a
      stereospecific rearrangement leading to the corresponding DEFG ring 4 of
      chloropeptin I.

PMID- 17497872
TI  - Thermal denaturation and aggregation properties of Atlantic salmon myofibrils and
      myosin from white and red muscles.
AB  - Thermal denaturation and aggregation abilities of salmon myofibrils and myosin
      were studied measuring turbidity, intrinsic fluorescence, 8-anilino-1-naphthalene
      sulfonic acid binding, and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide cross
      linking. The thermal behaviors of protein preparation from white and red muscles
      were compared, and the relationship with thermal gelation properties is
      discussed. The low gelation ability of salmon muscle proteins was related to a
      limited extent of protein denaturation and aggregation upon heating. These
      properties seemed to be carried by myosin molecules as a similar behavior was
      observed for both myofibrils and myosin preparations. The higher thermal
      stability observed for red muscle proteins with higher transition temperatures in
      rheological profiles was related to a shift to higher temperature in denaturation
      and aggregation processes. The extent of denaturation and aggregation was very
      similar for both muscle types as was the final rigidity of the gels formed.

PMID- 17497873
TI  - Anhydrous goat's milk fat: thermal and structural behaviors studied by coupled
      differential scanning calorimetry and X-ray diffraction. 2. Influence of cooling
      rate.
AB  - Crystallization and melting properties of triacylglycerols (TGs) in anhydrous
      goat's milk fat (AGMF) are investigated by X-ray diffraction as a function of
      temperature (XRDT) coupled with high-sensitivity differential scanning
      calorimetry (DSC), using synchrotron radiation and Microcalix. The polymorphic
      behavior of AGMF was monitored by varying the cooling rates between 5 and 1
      degrees C/min from 45 to -20 degrees C with their subsequent melting at 1 degrees
      C/min. Quenching of AGMF at -20 degrees C was also examined to determine the
      metastable polymorphic form of AGMF. At intermediate cooling rates, TGs in AGMF
      crystallize, from about 18 degrees C in two different lamellar structures with
      triple chain length 3Lalpha stacking of 72 A and a double chain length 2Lalpha
      stacking of 48 A, which are correlated to two overlapped exothermic peaks
      recorded by DSC. A reversible transition sub alpha <--> alpha was observed.
      Subsequent heating at 1 degrees C/min shows numerous structural rearrangements
      before final melting. At fast cooling of AGMF (5 degrees C/min), similar unstable
      crystalline varieties are formed while three endotherms are recorded. Several new
      unstable lamellar structures are observed after quenching. All of these data are
      compared to those previously reported at slow cooling (0.1 degrees C/min) showing
      a relative stability of the structures formed. In spite of general similitude,
      the thermal and structural behavior of the goat's milk is more complex than that
      of the cow's milk.

PMID- 17497874
TI  - Changes of folates, dietary fiber, and proteins in wheat as affected by
      germination.
AB  - Wheat kernels of the cultivar 'Tommi' were germinated for up to 168 h at 15, 20,
      25, or 30 degrees C. Samples were taken at different stages of germination and
      were analyzed for the quantitative protein composition using an extraction/HPLC
      method, for folate vitamers using a stable isotope dilution assay, and for
      soluble, insoluble, and total dietary fiber using a gravimetric method. Gluten
      proteins were substantially degraded during germination. During the first stages
      of germination the degradation of glutenins was predominant, whereas longer
      germination times were required to degrade gliadins. The optimal temperature for
      gliadin degradation was 20 degrees C, and that for glutenin degradation was 25
      degrees C. Omega5- and omega1,2-gliadins were less sensitive to proteolytic
      degradation than alpha- and gamma-gliadins, and LMW subunits of glutenin were
      less sensitive than HMW subunits. During germination a time- and temperature
      dependent increase of total folate occurred. A maximum 3.6-fold concentration was
      obtained after 102 h of germination at 20 and 25 degrees C including 5
      methyltetrafolate as the major vitamer. The concentration of dietary fiber
      remained constant or decreased during the first 96 h of germination. Prolonged
      germination times of up to 168 h led to a substantial increase of total dietary
      fiber and to a strong increase of the soluble dietary fiber by a factor of 3,
      whereas the insoluble fiber decreased by 50%.

PMID- 17497875
TI  - Effect of Albizia julibrissin water extracts on low-density lipoprotein
      oxidization.
AB  - High-value phytochemicals could be extracted from biomass prior to the current
      cellulosic pretreatment technologies (i.e., lime, ammonia, dilute acid, or
      pressurized hot water treatments) provided that the extraction is performed with
      a solvent that is compatible with the pretreatment. This work reports on the
      extraction of flavonoids from Albizia julibrissin biomass. While extracting A.
      julibrissin foliage with 50 degrees C water, 2.227 mg/g of hyperoside and 8.134
      mg/g quercitrin were obtained, which is in the realm of what was obtained with
      60% methanol. A. julibrissin foliage, flower, and whole plant extracts were
      tested in terms of their potential to inhibit low-density lipoprotein (LDL)
      oxidization. The highest inhibition was obtained with foliage water extracts,
      which were standardized at 2.5 microM of flavonoids. Also, the 2.5 microM foliage
      water extract resulted in a reduction from 43% to only 1% of the observed
      monocyte adherence. To have commercial application, A. julibrissin water extracts
      should be devoid of toxicity. The A. julibrissin foliage, flower, and whole plant
      water extracts were not toxic to Vero 76 cells. In summary, A. julibrissin
      biomass can be extracted with 50 degrees C water to yield an antioxidant stream,
      showing that it may be possible to couple extraction of valuable phytochemicals
      to the cellulosic pretreatment step.

PMID- 17497876
TI  - Membrane toxicity of antimicrobial compounds from essential oils.
AB  - Natural antimicrobial compounds perform their action mainly against cell
      membranes. The aim of this work was to evaluate the interaction, meant as a
      mechanism of action, of essential oil antimicrobial compounds with the microbial
      cell envelope. The lipid profiles of Escherichia coli O157:H7, Staphylococcus
      aureus, Salmonella enterica serovar Typhimurium, Pseudomonas fluorescens, and
      Brochothrix thermosphacta cells treated with thymol, carvacrol, limonene,
      eugenol, and cinnamaldehyde have been analyzed by gas chromatography. In line
      with the fatty acids analysis, the treated cells were also observed by scanning
      electron microscopy (SEM) to evaluate structural alterations. The overall results
      showed a strong decrease of the unsaturated fatty acids (UFAs) for the treated
      cells; in particular, the C18:2trans and C18:3cis underwent a notable reduction
      contributing to the total UFA decreases, while the saturated fatty acid C17:0
      raised the highest concentration in cinnamaldehyde-treated cells. SEM images
      showed that the used antimicrobial compounds quickly exerted their antimicrobial
      activities, determining structural alterations of the cell envelope.

PMID- 17497877
TI  - High throughput analysis of red wine and grape phenolics-adaptation and
      validation of methyl cellulose precipitable tannin assay and modified Somers
      color assay to a rapid 96 well plate format.
AB  - The methyl cellulose precipitable (MCP) tannin assay and a modified version of
      the Somers and Evans color assay were adapted to high-throughput (HTP) analysis.
      To improve efficiency of the MCP tannin assay, a miniaturized 1 mL format and a
      HTP format using 96 well plates were developed. The Somers color assay was
      modified to allow the standardization of pH and ethanol concentrations of wine
      samples in a simple one-step dilution with a buffer solution, thus removing
      inconsistencies between wine matrices prior to analysis and allowing for its
      adaptation to a HTP format. Validation studies showed that all new formats were
      efficient, and results were reproducible and analogous to the original formats.

PMID- 17497878
TI  - Characterization of humic substances derived from swine manure-based compost and
      correlation of their characteristics with reactivities with heavy metals.
AB  - Various composts contain a significant amount of humic substances including humic
      acid (HA) and fulvic acids (FAs). The FA fraction in soils is considered to be
      sensitive to agronomic and environmental factors. In this study, three fractions
      of humic substances, HA (MW > 1000 Da), FA (MW > 1000 Da), and FA (MW < 1000 Da)
      were extracted from swine manure-based compost and characterized, and then, their
      reactivities were correlated with heavy metals. Compositions of the three
      fractions of humic substances were characterized by elemental and total acidity
      analyses and electron spin resonance (ESR), Fourier transform infrared (FTIR),
      and 13C nuclear magnetic resonance with cross-polarization and magic-angle
      spinning spectroscopic techniques. Elemental analyses indicated that HA has
      higher contents of C, H, N, and S than those of FAs. However, FA (MW > 1000) and
      especially FA (MW < 1000) have higher contents of O than that of HA (MW > 1000).
      The g values of the ESR spectra of the three fractions showed that the organic
      free radical characteristics and the widths of the spectra and free radical
      concentrations of the three fractions are significantly different. The FTIR
      spectra indicated that HA (MW > 1000) is abundant in C=C bonds while FA (MW >
      1000), especially FA (MW < 1000), are abundant in C=O bonds. In addition, 13C NMR
      spectra indicate that carboxyl contents of FA (MW > 1000), especially FA (MW <
      1000), are higher than that of HA (MW > 1000). The sequence of the reactivity in
      terms of acidic functional groups was FA (MW < 1000) > FA (MW > 1000) > HA (MW >
      1000). Elemental and functional group compositions of the three fractions
      significantly correlated with reported reactivities with heavy metals. The
      application of swine manure-based compost containing HA and FAs fractions to soil
      and associated environments may thus significantly affect the concerned reactions
      with organic and inorganic compounds including pollutants.

PMID- 17497879
TI  - Mild photochemical synthesis of the antioxidant hydroxytyrosol via conversion of
      tyrosol.
AB  - Hydroxytyrosol, a naturally occurred orthodiphenolic antioxidant molecule found
      in olive oil and olive mill wastewaters, was obtained from the wet hydrogen
      peroxide photocatalytic oxidation of its monophenolic precursor tyrosol. The
      liquid-phase oxidation of tyrosol to hydroxytyrosol was performed by use of an
      iron-containing heterogeneous catalyst (Al-Fe)PILC with the assistance of UV
      irradiation at 254 nm and at room temperature. The spectroscopic and HPLC data of
      the synthesized compound proved to coincide fully with those of a pure sample
      obtained by continuous countercurrent extraction. This reaction was found to be
      light-induced. The hydroxytyrosol synthesis reaction reached its maximum yield of
      64.36% under the optimized operating conditions of 3.6 mM tyrosol, 0.5 g L(-1)
      catalyst, and 10(-2) M H2O2 with the assistance of UV light. Increasing the
      initial hydrogen peroxide concentration more than 10(-2) M has a diminishing
      return on the reaction efficiency. Catalyst can be recuperated by means of
      filtration and then reused in a next run after regeneration since its activity
      did not significantly decrease (<10%). The reaction synthesis is operationally
      simple and could find application for industrial purposes.

PMID- 17497880
TI  - Cloning and characterization of a catechol-degrading gene cluster from 3,4
      dichloroaniline degrading bacterium Pseudomonas sp. KB35B.
AB  - We recently isolated a bacterium, Pseudomonas sp. KB35B, capable of growth on 3,4
      dichloroaniline (DCA) as a sole carbon source. The isolated strain showed a high
      level of catechol 2,3-dioxygenase (CD-2,3) activity in the presence of 3,4-DCA.
      In an attempt to elucidate the relationship between biodegradation of 3,4-DCA and
      CD-2,3 activity, the genes encoding enzymes for the catabolic pathway of catechol
      were cloned and sequenced from the chromosomal DNA. The sequence analysis of the
      10752 bp DNA fragment revealed 12 open reading frames in the order of
      nahRGTHINLOMKJX. Among the 12 genes, nahHINLOMK genes encode enzymes for the
      metabolism of catechol to TCA cycle intermediates. The nahR gene is the LysR type
      transcriptional regulator, and the nahH gene encodes CD-2,3 for meta-cleavages of
      catechol. 2-Hydroxymuconic semialdehyde hydrolase, 2-oxypent-4-dienoate
      hydratase, and 4-hydroxy-2-oxovalerate aldolase encoded by nahLMN genes are
      responsible for the three steps after meta-cleavages of catechol. The current
      results suggested that Pseudomonas sp. KB35B degrades 3,4-DCA via the meta
      cleavage pathway of catechol.

PMID- 17497881
TI  - Evaluation of the influence of thermal oxidation on the phenolic composition and
      on the antioxidant activity of extra-virgin olive oils.
AB  - A comparison between the results obtained by using HPLC-UV, HPLC-MS, and CE-UV
      for characterizing the deterioration of extra-virgin olive oil during heating
      (180 degrees C) was investigated, taking into account phenolic compounds. The
      concentration of several compounds belonging to four families of phenols (simple
      phenols, lignans, complex phenols, and phenolic acids) was determined in the
      samples after the thermal treatment by all three techniques. Hydroxytyrosol,
      elenolic acid, decarboxymethyl oleuropein aglycon, and oleuropein aglycon reduced
      their concentration with the thermal treatment more quickly than other phenolic
      compounds present in olive oil. HYTY-Ac and Lig Agl were demonstrated to be quite
      resistant to this kind of treatment, and the behavior of lignans could be
      outstanding, as they belong to the family most resistant to thermal treatment.
      Several "unknown" compounds were determined in the phenolic profiles of the oils
      after the thermal treatment, and their presence was confirmed in refined olive
      oils. The oxidative stability index (OSI time) was reduced from 25 to 5 h after 3
      h of heating, whereas the peroxide value showed a minimum after 1 h of heating.

PMID- 17497882
TI  - Tissue distribution of lignans in rats in response to diet, dose-response, and
      competition with isoflavones.
AB  - This paper investigates the occurrence and distribution of the lignan metabolites
      enterodiol (END) and enterolactone (ENL) and the isoflavone daidzein (DAID) in
      rat tissues by use of liquid chromatography-electrospray ionization mass
      spectrometry (LC-ESI/MSn) following a variety of dietary regimes. Furthermore, we
      examined the dose-response and distribution of END and ENL in liver, testes,
      prostate, and lung, and we investigated the effects of competition between
      lignans and isoflavones on metabolite distribution. In liver, testes, prostate,
      and lung tissue, dose-related increases in END concentration were observed. In
      the testes, coadministration of 60 mg/kg secoisolariciresinol diglycoside (SDG)
      with 60 mg/kg isoflavones produced alterations in the resulting metabolite
      profile, causing increased END concentration and decreased DAID concentration.
      Results indicate lignan accumulation in tissues occurs, and coadministration of
      lignans with isoflavones affects the metabolite profile, with effects dependent
      on tissue type.

PMID- 17497883
TI  - Effects of conservation treatment and cooking on the chemical composition and
      antioxidant activity of Portuguese wild edible mushrooms.
AB  - The effects of processing and cooking practices on the chemical composition and
      antioxidant activity of Portuguese wild edible mushroom species (Lactarius
      deliciosus, Macrolepiota mastoidea, Macrolepiota procera, and Sarcodon
      imbricatus) were investigated. Dried, frozen, and cooked samples were analyzed
      for proximate constituents (moisture, fat, crude protein, ash, and carbohydrates)
      and nutritional value. Fatty acid and sugar profiles were also obtained by gas
      liquid chromatography/flame ionization detection and high-performance liquid
      chromatography/refraction index, respectively. The antioxidant properties were
      evaluated by several biochemical assays: 2,2-diphenyl-1-picrylhydrazyl radical
      scavenging capacity, reducing power, inhibition of beta-carotene bleaching, and
      inhibition of lipid peroxidation in brain tissue using thiobarbituric acid
      reactive substances. Results of this study show that mushroom species and
      processing and cooking practices are all effective determinants for either
      chemical composition or antioxidant properties. Cooked samples proved to have
      lower nutrient concentrations and lower antioxidant activities than either dried
      or frozen samples. In what concerns fatty acids and sugar individual profiles,
      only cooking proved to be relevant: The cooked samples presented higher
      monounsaturated fatty acid and lower polyunsaturated fatty acid and sugars
      contents.

PMID- 17497884
TI  - Evaluation of fatty acid extraction methods for Thraustochytrium sp. ONC-T18.
AB  - Various extraction methods were assessed in their capacity to extract fatty acids
      from a dried biomass of Thraustochytrium sp. ONC-T18. Direct saponification using
      KOH in ethanol or in hexane:ethanol was one of the most efficient techniques to
      extract lipids (697 mg g(-1)). The highest amount of fatty acids (714 mg g(-1))
      was extracted using a miniaturized Bligh and Dyer extraction technique. The use
      of ultrasonics to break down cell walls while extracting with solvents
      (methanol:chloroform) also offered high extraction yields of fatty acids (609 mg
      g(-1)). Moreover, when the transesterification mixture used for a direct
      transesterification method was doubled, the extraction of fatty acids increased
      approximately 77% (from 392 to 696 mg g(-1)). This work showed that
      Thraustochytrium sp. ONC-T18 has the ability to produce over 700 mg g(-1) of
      lipids, including more than 165 mg g(-1) of docosahexaenoic acid, which makes
      this microorganism a potential candidate for the commercial production of
      polyunsaturated fatty acids. Finally, other lipids, such as myristic, palmitic,
      palmitoleic, and oleic acids, were also produced and recovered in significant
      amounts (54, 196, 123, and 81 mg g(-1)), respectively.

PMID- 17497885
TI  - Screening for pharmaceutical cocrystal hydrates via neat and liquid-assisted
      grinding.
AB  - The formation of cocrystal hydrates represents a potential route to achieve
      molecular materials with improved properties, particularly stability under
      conditions of high relative humidity. We describe the use of neat and liquid
      assisted grinding for screening for hydrated forms of pharmaceutical cocrystals.
      In the case of liquid-assisted grinding, water is present in the reaction mixture
      as a liquid, whereas in the case of neat grinding, it is introduced by employing
      crystalline hydrates as reactants. The ability to form a cocrystal hydrate by
      either of the two methods appears to be variable, depending on the choice of
      cocrystal components. Theophylline readily forms a cocrystal hydrate with citric
      acid. This contrasts with the behavior of caffeine, which provides only an
      anhydrous cocrystal ("caffeine citrate") even when both reactants are crystalline
      hydrates. The preference of theophylline to form a cocrystal hydrate is
      qualitatively explained by similarity between crystal structures of the products
      and reactant hydrates. Overall, liquid-assisted grinding is less sensitive to the
      form of the reactant (i.e., hydrate or anhydrate) than neat grinding. For that
      reason liquid-assisted grinding appears to be a more efficient method of
      screening for cocrystal hydrates, and it is also applicable to screening for
      hydrates of APIs.

PMID- 17497887
TI  - Supramolecular medicinal chemistry: mixed-ligand coordination complexes.
AB  - We report on the supramolecular synthesis and characterization of examples from
      three series of mixed-ligand coordination complexes composed of copper(II), a
      drug, and an ancillary ligand (AL). Particularly, we demonstrate how the
      judicious choice of an ancillary ligand affords a large degree of control over
      the relative lipophilicity/hydrophilicity of the complex in relation to the
      uncomplexed drug molecule. Furthermore, we demonstrate several important factors
      to consider in the design of such complexes such as the additive-constitutive
      nature of the partition coefficient of the ancillary ligand and the relative size
      of the two types of ligands.

PMID- 17497886
TI  - Celecoxib:nicotinamide dissociation: using excipients to capture the cocrystal's
      potential.
AB  - The cocrystal of celecoxib and nicotinamide (Cel:Nic) was crystallized from
      chloroform in a 1:1 ratio, and the structure has been solved from powder X-ray
      diffraction data. The dissolution and solubility of Cel:Nic are medium dependent
      and can be attributed to differences in conversion of Cel:Nic to celecoxib
      polymorphs I and III (Cel-I and Cel-III). The presence of low concentrations of
      surfactants facilitates the rapid conversion of neat Cel:Nic to large aggregates
      of Cel-III that dissolve more slowly than commercial Cel-III into 1% SDS
      solution. In contrast, combinations of Cel:Nic with both 1-10% solid SDS and PVP
      wet rapidly and convert to a mixture of amorphous celecoxib and a micron-sized
      crystalline celecoxib form IV (Cel-IV), which has recently been shown to be up to
      4-fold more bioavailable than marketed Cel-III. More than 90% of the suspended
      material dissolves within 2 min at 37 degrees C when transferred to 1% SDS
      solution. This example highlights the importance of exploring the form conversion
      of cocrystals in aqueous media prior to pharmacokinetic studies, and illustrates
      the potential of simple formulations to overcome the limitations caused by rapid
      dissociation of cocrystals and recrystallization of poorly soluble forms in
      aqueous media.

PMID- 17497888
TI  - Amide-N-oxide heterosynthon and amide dimer homosynthon in cocrystals of
      carboxamide drugs and pyridine N-oxides.
AB  - The carboxamide-pyridine N-oxide heterosynthon is sustained by syn(amide)N-H...O
      (oxide) hydrogen bond and auxiliary (N-oxide)C-H...O(amide) interaction (Reddy,
      L. S.; Babu, N. J.; Nangia, A. Chem. Commun. 2006, 1369). We evaluate the scope
      and utility of this heterosynthon in amide-containing molecules and drugs (active
      pharmaceutical ingredients, APIs) with pyridine N-oxide cocrystal former
      molecules (CCFs). Out of 10 cocrystals in this study and 7 complexes from
      previous work, amide-N-oxide heterosynthon is present in 12 structures and amide
      dimer homosynthon occurs in 5 structures. The amide dimer is favored over amide-N
      oxide synthon in cocrystals when there is competition from another H-bonding
      functional group, e.g., 4-hydroxybenzamide, or because of steric factors, as in
      carbamazepine API. The molecular organization in carbamazepine.quinoxaline N,N'
      dioxide 1:1 cocrystal structure is directed by amide homodimer and anti(amide)N
      H...O-(oxide) hydrogen bond. Its X-ray crystal structure matches with the third
      lowest energy frame calculated in Polymorph Predictor (Cerius(2), COMPASS force
      field). Apart from generating new and diverse supramolecular structures,
      hydration is controlled in one substance. 4-Picoline N-oxide deliquesces within a
      day, but its cocrystal with barbital does not absorb moisture at 50% RH and 30
      degrees C up to four weeks. Amide-N-oxide heterosynthon has potential utility in
      both amide and N-oxide type drug molecules with complementary CCFs. Its
      occurrence probability in the Cambridge Structural Database is 87% among 27
      structures without competing acceptors and 78% in 41 structures containing OH,
      NH, H(2)O functional groups.

PMID- 17497889
TI  - Singlet oxygen generation from the decomposition of alpha-linolenic acid
      hydroperoxide by cytochrome c and lactoperoxidase.
AB  - Generation of singlet oxygen is first investigated in the decomposition of
      polyunsaturated lipid peroxide, alpha-linolenic acid hydroperoxide (LAOOH), by
      heme-proteins such as cytochrome c and lactoperoxidase. Chemiluminescence and
      electron spin resonance methods are used to confirm the singlet oxygen generation
      and quantify its yield. Decomposition products of LAOOH are characterized by HPLC
      ESI-MS, which suggests that singlet oxygen is produced via the decomposition of a
      linear tetraoxide intermediate (Russell's mechanism). Free radicals formed in the
      decomposition are also identified by the electron spin resonance technique, and
      the results show that peroxyl, alkyl, and epoxyalkyl radicals are involved. The
      changes of cytochrome c and lactoperoxidase in the reaction are monitored by UV
      visible spectroscopy, revealing the action of a monoelectronic and two-electronic
      oxidation for cytochrome c and lactoperoxidase, respectively. These results
      suggest that cytochrome c causes a homolytic reaction of LAOOH, generating
      alkoxyl radical and then peroxyl radical, which in turn releases singlet oxygen
      following the Russell mechanism, whereas lactoperoxidase leads to a heterolytic
      reaction of LAOOH, and the resulting ferryl porphyryl radical of lactoperoxidase
      abstracts the hydrogen atom from LAOOH to give peroxyl radical and then singlet
      oxygen. This observation would be important for a better understanding of the
      damage mechanism of cell membrane or lipoprotein by singlet oxygen and various
      radicals generated in the peroxidation and decomposition of lipids induced by
      heme-proteins.

PMID- 17497890
TI  - Peptidyl boronates inhibit Salmonella enterica serovar Typhimurium Lon protease
      by a competitive ATP-dependent mechanism.
AB  - Lon is a homo-oligomeric ATP-dependent serine protease that functions in the
      degradation of damaged and certain regulatory proteins. This enzyme has emerged
      as a novel target in the development of antibiotics because of its importance in
      conferring bacterial virulence. In this study, we explored the mechanism by which
      the proteasome inhibitor MG262, a peptidyl boronate, inhibits the peptide
      hydrolysis activity of Salmonella enterica serovar Typhimurium Lon. In addition,
      we synthesized a fluorescent peptidyl boronate inhibitor based upon the amino
      acid sequence of a product of peptide hydrolysis by the enzyme. Using steady
      state kinetic techniques, we have shown that two peptidyl boronate variants are
      competitive inhibitors of the peptide hydrolysis activity of Lon and follow the
      same two-step, time-dependent inhibition mechanism. The first step is rapid and
      involves binding of the inhibitor and formation of a covalent adduct with the
      active site serine. This is followed by a second slow step in which Lon undergoes
      a conformational change or isomerization to increase the interaction of the
      inhibitor with the proteolytic active site to yield an overall inhibition
      constant of 5-20 nM. Although inhibition of serine and threonine proteases by
      peptidyl boronates has been detected previously, Lon is the first protease that
      has required the binding of ATP in order to observe inhibition.

PMID- 17497891
TI  - Probing DNA polymerase-DNA interactions: examining the template strand in
      exonuclease complexes using 2-aminopurine fluorescence and acrylamide quenching.
AB  - The bacteriophage T4 DNA polymerase forms fluorescent complexes with DNA
      substrates labeled with 2-aminopurine (2AP) in the template strand; the
      fluorescence intensity depends on the position of 2AP. When preexonuclease
      complexes are formed, complexes at the crossroads between polymerase and
      exonuclease complexes, 2AP in the +1 position in the template strand is fully
      free of contacts with the adjacent bases as indicated by high fluorescence
      intensity and a long fluorescence lifetime of about 10.9 ns. Fluorescence
      intensity decreases for 2AP in the template strand when the primer end is
      transferred to the exonuclease active center to form exonuclease complexes, which
      indicates a change in DNA conformation; 2AP can now interact with adjacent bases,
      which quenches fluorescence emission. Some polymerase-induced base unstacking for
      2AP in the template strand in exonuclease complexes is observed but is restricted
      primarily to the n and +1 positions, which indicates that the DNA polymerase
      holds the template strand in a way that forces base unstacking only in a small
      region near the primer terminus. A hold on the template strand will help to
      maintain the correct alignment of the template and primer strands during
      proofreading. Acrylamide quenches 2AP fluorescence in preexonuclease and in
      exonuclease complexes formed with DNA labeled with 2AP in the template strand,
      which indicates that the template strand remains accessible to solvent in both
      complexes. These studies provide new information about the conformation of the
      template strand in exonuclease complexes that is not available from structural
      studies.

PMID- 17497892
TI  - Discovery, synthesis, and structure activity of a highly selective alpha7
      nicotinic acetylcholine receptor antagonist.
AB  - Nicotinic acetylcholine receptors (nAChRs) that contain an alpha7 subunit are
      widely distributed in neuronal and nonneuronal tissue. These receptors are
      implicated in the release of neurotransmitters such as glutamate and in functions
      ranging from thought processing to inflammation. Currently available ligands for
      alpha7 nAChRs have substantial affinity for one or more other nAChR subtypes,
      including those with an alpha1, alpha3, alpha6, and/or alpha9 subunit. An alpha
      conotoxin gene was cloned from Conus arenatus. Predicted peptides were
      synthesized and found to potently block alpha3-, alpha6-, and alpha7-containing
      nAChRs. Structure-activity information regarding conotoxins from distantly
      related Conus species was employed to modify the C. arenatus derived toxin into a
      novel, highly selective alpha7 nAChR antagonist. This ligand, alpha
      CtxArIB[V11L,V16D], has low nanomolar affinity for rat alpha7 homomers expressed
      in Xenopus laevis oocytes, and antagonism is slowly reversible. Kinetic analysis
      provided insight into the mechanism of antagonism. alpha-CtxArIB interacts with
      five ligand binding sites per alpha7 receptor, and occupation of a single site is
      sufficient to block function. The peptide was also shown to be highly selective
      in competition binding assays in rat brain membranes. alpha-CtxArIB[V11L,V16D] is
      the most selective ligand yet reported for alpha7 nAChRs.

PMID- 17497893
TI  - FTIR study on the hydrogen bond structure of a key tyrosine residue in the flavin
      binding blue light sensor TePixD from Thermosynechococcus elongatus.
AB  - The BLUF (sensor of blue light using FAD) domain is a blue light receptor
      possessing a flavin molecule as an active cofactor. A conserved Tyr residue
      located adjacent to flavin has been proposed to be a key amino acid in the
      mechanism of the photoreaction of the BLUF domain. We have studied the structure
      of this key Tyr residue and the relevance to the photoreaction in the BLUF
      protein of the cyanobacterium Thermosynechococcus elongatus, TePixD, by means of
      Fourier transform infrared (FTIR) difference spectroscopy and density functional
      theory (DFT) calculations. Light-induced FTIR difference spectra of unlabeled and
      [4-13C]Tyr-labeled TePixD in H2O and D2O revealed that the nuCO/deltaCOH
      vibrations of a photosensitive Tyr side chain are located at 1265/1242 cm-1 in
      the dark-adapted state and at 1273/1235 cm-1 in the light-induced signaling
      state. These signals were assigned to the vibrations of Tyr8 near flavin from the
      absence of the effect of [4-13C]Tyr labeling in the Tyr8Phe mutant. DFT
      calculations of H-bonded complexes of p-cresol with amides as models of the Tyr8
      Gln50 interactions showed that Tyr8 acts as a H-bond donor to the Gln50 in both
      of the dark and light states. Further DFT analysis suggested that this H-bond is
      strengthened upon photoconversion to the light state accompanied with a change in
      the H-bond angle. The change in the H-bond structure of Tyr8 is coupled to the
      flavin photoreaction probably through the Tyr8-Gln50-flavin H-bond network,
      suggesting a significant role of Tyr8 in the photoreaction mechanism of TePixD.

PMID- 17497895
TI  - Nucleobase-dependent reactivity of a quinone metabolite of pentachlorophenol.
AB  - Pentachlorophenol (PCP) is a possible human carcinogen detected widely in the
      environment. A quinone metabolite of PCP, tetrachloro-1,4-benzoquinone (Cl4BQ),
      is a reactive electrophile with the capacity to damage DNA by forming bulky
      covalent DNA adducts. These quinone adducts may contribute to chlorophenol
      carcinogenesis, but their structures, occurrence, and biological consequences are
      not known. Previous studies have indicated that several DNA adducts are formed in
      vivo in rats exposed to Cl4BQ, but these adducts were not identified
      structurally. In the present study, we have elucidated the structure of new agent
      specific DNA adducts resulting from the reaction of dGuo, dCyd, and Thd with
      Cl4BQ. These have been characterized chemically by liquid chromatography
      electrospray ionization mass spectrometry, HPLC, UV, and NMR analysis. Two dGuo
      adducts and one dCyd adduct resulting from the reaction of double-stranded DNA
      with Cl4BQ have been identified. The results indicate that, in the structural
      context of DNA, Cl4BQ reacts most readily with dGuo compared to the other DNA
      bases and that the mode of Cl4BQ reactivity is dependent on the base structure;
      i.e., multiple types of adducts are formed. Finally, DNA adducts consistent with
      Cl4BQ reactions are observed when DNA or dGuo is treated with PCP and a
      peroxidase-based bioactivating system.

PMID- 17497897
TI  - Time-dependent inactivation of P450 3A4 by raloxifene: identification of Cys239
      as the site of apoprotein alkylation.
AB  - Time-dependent inactivation of cytochrome P450s is typically a result of
      substrate bioactivation to form reactive species that subsequently alkylate the
      heme group, apoprotein, or both. The chemical identity of many reactive
      intermediates is generally proposed based on the products of trapping reactions
      with nucleophilic agents as only a few P450-drug adducts have been directly
      characterized. We describe the use of mass spectrometry to show that a single
      equivalent of raloxifene is bound to the intact P450 apoprotein. Furthermore,
      mass analysis of peptides following digestion with proteinase K revealed that the
      covalently bound drug is localized to residue Cys239. A mass shift of 471 Da to
      the intact protein and peptide, relative to control samples, indicated that time
      dependent inactivation of P450 3A4 occurred through the raloxifene diquinone
      methide intermediately prior to nucleophilic attack of the sulfur of Cys239.
      Association between raloxifene adduction to P450 3A4 apoprotein and the observed
      time-dependent inactivation was further investigated with the use of cysteine
      specific modifying reagents. When P450 3A4 was treated with iodoacetamide or N-(1
      pyrene)iodoacetamide, which alkylated residue Cys239 exclusively, time-dependent
      inactivation of P450 3A4 by raloxifene was prevented. The change in protein mass
      of 471 Da combined with the protection from inactivation that occurred through
      pre-alkylation of Cys239 provided conclusive evidence that raloxifene-mediated
      P450 3A4 inactivation occurred through the bioactivation of raloxifene to the
      diquinone methide and subsequent alkylation of Cys239.

PMID- 17497896
TI  - Inactivation of anthracyclines by serum heme proteins.
AB  - We have previously shown that the anticancer agent doxorubicin undergoes
      oxidation and inactivation when exposed to myeloperoxidase-containing human
      leukemia HL-60 cells, or to isolated myeloperoxidase, in the presence of hydrogen
      peroxide and nitrite. In the current study we report that commercial fetal bovine
      serum (FBS) alone oxidizes doxorubicin in the presence of hydrogen peroxide and
      that nitrite accelerates this oxidation. The efficacy of inactivation was
      dependent on the concentration of serum present; no reaction was observed when
      hydrogen peroxide or serum was omitted. Peroxidase activity assays, based on
      oxidation of 3,3',5,5'-tetramethylbenzidine, confirmed the presence of a
      peroxidase in the sera from several suppliers. The peroxidative activity was
      contained in the >10000 MW fraction. We also found that hemoglobin, a heme
      protein likely to be present in commercial FBS, is capable of oxidizing
      doxorubicin in the presence of hydrogen peroxide and that nitrite further
      stimulates the reaction. In contrast to intact doxorubicin, the serum + hydrogen
      peroxide + nitrite treated drug appeared to be nontoxic for PC3 human prostate
      cancer cells. Together, this study shows that (pseudo)peroxidases present in sera
      catalyze oxidation of doxorubicin by hydrogen peroxide and that this diminishes
      the tumoricidal activity of the anthracycline, at least in in vitro settings.
      Finally, this study also points out that addition of H2O2 to media containing FBS
      will stimulate peroxidase-type of reactions, which may affect cytotoxic
      properties of studied compounds.

PMID- 17497898
TI  - Role of carbonate in the cytotoxicity of carboplatin.
AB  - Carboplatin, [Pt(NH3)2(CBDCA-O,O')], 1, where CBDCA is cyclobutane-1,1
      dicarboxylate, is used against ovarian, lung, and other types of cancer. We
      recently showed (Di Pasqua et al. (2006) Chem. Res. Toxicol. 19, 139-149) that
      carboplatin reacts with carbonate under conditions that simulate therapy to
      produce carbonato carboplatin, cis-[Pt(NH3)2(O-CBDCA)(CO3)]2-, 2. We use 13C and
      1H NMR and UV-visible absorption spectroscopy to show that solutions containing
      carboplatin that have been aged in carbonate buffer under various conditions
      contain 1, 2, and other compounds. We then show that aging carboplatin in
      carbonate produces compounds that are more toxic to human neuroblastoma (SK-N
      SH), proximal renal tubule (HK-2) and Namalwa-luc Burkitt's lymphoma (BL) cells
      than carboplatin alone. Moreover, increasing the aging time increases the
      cytotoxicity of the platinum solutions as measured by the increase in cell death.
      Although HK-2 cells experience a large loss in survival upon exposure to
      carbonato forms of the drug, they have the highest values of IC50 of the three
      cell lines studied, so that HK-2 cells remain the most resistant to the toxic
      effects of the carbonato forms in the culture medium. This is consistent with the
      well-known low renal toxicity observed for carboplatin in therapy. The uptake
      rates for normal Jurkat cells (NJ) and cisplatin-resistant Jurkat cells (RJ),
      measured by inductively coupled plasma mass spectrometry (ICP-MS), are 16.6 +/-
      4.2 and 12.3 +/- 4.8 amol of Pt h-1 cell-1, respectively, when exposed to
      carboplatin alone. However, when these cells are exposed to carboplatin that has
      been aged in carbonate media, normal Jurkat cells strongly bind/take up Pt at a
      rate of 14.5 +/- 4.1 amol of Pt h-1 cell-1, while resistant cells strongly
      bind/take up 5.1 +/- 3.3 amol of Pt h-1 cell-1. Collectively, these studies show
      that carboplatin carbonato species may play a major role in the cytotoxicity and
      uptake of carboplatin by cells.

PMID- 17497899
TI  - Brownian dynamics simulations of associating diblock copolymers.
AB  - A novel coarse-grained computational model for associating polymers is proposed
      that is based on a Gaussian "blob" representation of the polymer chains. The
      model allows a large number of model polymers to be simulated at moderate
      computational cost over a wide packing fraction range using the Brownian
      dynamics, BD, technique. The attraction of the hydrophobic part of the polymer to
      those on other molecules can lead to strong aggregation of the polymer molecules
      in real systems, and this is included in the model by an attractive potential
      felt by the Gaussian blobs to a common "nodal" point that represents the center
      of the micelle. Attention here is confined to model AB diblock copolymers in
      which the hydrophilic block, A, has a much higher mass than the hydrophobic
      moiety, B, which leads to relatively small aggregation numbers, Nagg, of
      approximately 8. The aggregation number at low packing fractions is found to
      increase with packing fraction, as observed in experiments, with a functional
      form that closely follows a simple theory derived here that is based on entropy
      derived mean-field terms for the free-energy change associated with the
      incorporation of the polymer molecule into the micelle. The computational model
      exhibits an extremely low critical micelle concentration (cmc), and micelles with
      Nagg approximately 5 are observed at the lowest packing fractions, phi, simulated
      ( approximately 10-4), which is consistent with experiment. The long-time self
      diffusion coefficient of the polymers (and hence micelles) decreases
      logarithmically with packing fraction, and the viscosity increased with
      concentration according to the Huggins equation. The spherical blob coarse
      graining results in the simulable time scales being longer than the Rouse time of
      the chain, and hence for the nonassociating polymers the intrinsic viscosity is
      an input parameter in the model. The introduction of association leads to the
      partial inclusion of the intrinsic viscosity in the simulation and has an effect
      on the computed Huggins coefficient, kH, which is found to be approximately 6 in
      those cases.

PMID- 17497900
TI  - Investigating the surface properties of Escherichia coli under glucose controlled
      conditions and its effect on aggregation.
AB  - Bacteria exist as aggregates or in biofilms to help with adaptation and
      protection from environmental stresses. The hypothesis that is tested in this
      paper is that the relative presence of glucose in the media, at the beginning of
      the growth phase, influences the surface chemistry of the cell, which as a
      consequence reduces the tendency for the cells to interact and form aggregates.
      In this study, we used Escherichia coli (E. coli) MG1655 as a model organism and
      measured the change in the surface chemistry of cells harvested at different
      growth phases, which had been cultured in Luria-Bertani media with and without
      the addition of glucose, using potentiometric titration and infrared
      spectroscopy. Cells, cultivated with the additional supplement of glucose at the
      beginning of the growth phase, displayed a higher concentration of bacterial
      surface functional groups and a variation in outer membrane proteins. As a
      consequence, the tendency for cell-to-cell attachment was significantly reduced.
      Our findings therefore revealed that glucose limits aggregation in E. coli MG1655
      by altering the concentration of functional groups from macromolecules present on
      the bacterial surface.

PMID- 17497901
TI  - Thermally controlled fluidic self-assembly.
AB  - A novel approach for the fluidic self-assembly (FSA) of microparts in a
      multibatch process utilizing the thermal behavior of the carrier fluid as a means
      for selecting binding sites is presented. In the system studied, fluidic assembly
      takes place due to a capillary bridge between hexadecane deposited on a
      hydrophobic patch on a substrate and a hydrophobic surface on a micropart
      suspended in a carrier fluid. When desired, FSA of microparts is prevented by
      causing the surrounding carrier fluid to form a gel when heated, offering a
      method for directing self-assembly to sites that are not heated. It is shown that
      a suitable carrier fluid is 15 wt % Pluronic F127, which gels at about 40 degrees
      C when tested in the geometry used to demonstrate the concept. Experimental
      results demonstrating FSA and thermally controlled fluidic assembly (TCFSA) of
      plastic microparts dispersed in Pluronic F127 solution are presented.
      Potentially, TCFSA offers a general method for directed assembly as it relies on
      restricting the transport of microparts to a site rather than interfering with
      the fundamental attractive forces responsible for self-assembly.

PMID- 17497902
TI  - Fluorescence correlation spectroscopy at the oil-water interface: hard disk
      diffusion behavior in dilute beta-lactoglobulin layers precedes monolayer
      formation.
AB  - We have performed a thorough characterization of fluorescence correlations
      spectroscopy (FCS) applied to oil-water interfaces of viscous oil droplets in
      aqueous solution, including numerical wave-optical calculations of the detection
      geometry and regularized multicomponent analysis of sample data. It is shown how
      significant errors in the estimation of the surface concentration can be avoided
      when FCS is applied to an interface region. We present data on the adsorption
      dynamics of beta-lactoglobulin (BLG), a well-studied model system. It is found
      that electrostatic repulsion slows the adsorption process and reduces the initial
      saturation density far below the monolayer concentration. During the first stages
      of adsorption, the diffusion coefficients of adsorbed protein closely follow the
      2D hard disk model of Lahtinen et al.1 in response to increased surface
      concentration, which suggests that protein-protein interactions are limited to
      long-range Coulombic interactions at this stage.

PMID- 17497903
TI  - In situ XAFS studies of Au particle formation by photoreduction in polymer
      solutions.
AB  - Formation mechanisms of metal particles (gold (Au) particles) in an aqueous
      ethanol solution of HAuCl4 with poly(N-vinyl-2-pyrrolidone) (PVP) by the
      photoreduction method were investigated by UV-vis, transmission electron
      microscopy (TEM), and in situ and ex situ X-ray absorption fine structure (XAFS)
      analysis. The average diameters of the dilute and concentrated Au particles in
      PVP solution are estimated from TEM to be 106 A and 925 A, respectively. XAFS
      analysis was carried out to elucidate the reduction process of AuCl4- ionic
      species to metallic Au particles for the Au-L3 edge of the colloidal dispersions
      of the concentrated Au solutions. In the photoreduction process, the reduction of
      AuCl2- species to Au0 atoms is a slower process than that of AuCl4- to AuCl2-,
      and the reduction of AuCl2- to Au0 atoms and the association of Au0 atoms to form
      seed Au particles (particle diameter between 5.5 and 30 A) concurrently proceeds
      in the short-duration photoirradiation. In addition, in the long-duration
      photoirradiation, the slow progression of Au particle growth occurs with the
      association of Au0-Au0 metallic bonds, resulting in the formation of larger Au
      particles (particle diameter larger than 500 A).

PMID- 17497904
TI  - Wetting-Dewetting oscillations of liquid films during solution-mediated vacuum
      deposition of rubrene.
AB  - We found a novel oscillating phenomenon associated with surface wetting during
      the vacuum deposition of an organic semiconductor (rubrene) on a liquid film
      (bis(2-ethylhexyl)sebacate, B2EHS). In-situ observations by an optical microscope
      revealed that the oscillation was associated with the growth of the rubrene
      crystals. The oscillation frequency was proportional to the evaporation rate of
      rubrene. On the basis of the contact angle measurements, it was concluded that
      the oscillation is probably due to the change in the contact angle of the liquid
      caused by the formation of ultrathin rubrene films on the liquid surface.

PMID- 17497905
TI  - Metabolic profiling analysis of a D-galactosamine/lipopolysaccharide-induced
      mouse model of fulminant hepatic failure.
AB  - The purpose of this study was to characterize the changes in metabolic
      intermediates and to investigate the metabolic profile of a mouse model of
      fulminant hepatic failure (FHF), induced by D-galactosamine/lipopolysaccharide
      (GalN/LPS). Plasma metabolite levels were detected using gas chromatography/time
      of-flight mass spectrometry, and the acquired data were transferred into Simca-P
      and processed using principal components analysis (PCA). In total, 45 metabolites
      were identified from the 267 distinct compounds found in the study. Whereas
      significant differences were noted in the plasma levels of the control and FHF
      groups, no differences in gluconeogenesis or glycolysis were noted following
      GalN/LPS treatment. Our data also suggest that the production of ketone bodies,
      and the tricarboxylic acid and urea cycles, was inhibited. PCA data suggest that
      5-hydroxyindoleacetic acid, glucose, beta-hydroxybutyrate, and phosphate
      parameters had the highest weights on each of the principal components, and that
      they were the most important metabolites contributing to the separation of
      groups. In conclusion, this metabonomic approach can be used as a powerful tool
      to characterize changes in metabolic intermediates and to search for metabolic
      markers under certain pathophysiological conditions, such as FHF. Our data also
      demonstrate that a combination of 5-hydroxyindoleacetic acid, glucose, beta
      hydroxybutyrate, and phosphate concentrations in the plasma is a potential marker
      for FHF, as well as for the early prognosis of FHF.

PMID- 17497906
TI  - A method for selective enrichment and analysis of nitrotyrosine-containing
      peptides in complex proteome samples.
AB  - Elevated levels of protein tyrosine nitration have been found in various
      neurodegenerative diseases and age-related pathologies. Until recently, however,
      the lack of an efficient enrichment method has prevented the analysis of this
      important low-level protein modification. We have developed a method that
      specifically enriches nitrotyrosine-containing peptides so that both
      nitrotyrosine peptides and specific nitration sites can be unambiguously
      identified with LC-MS/MS. The procedure consists of the derivatization of
      nitrotyrosine into free sulfhydryl groups followed by high efficiency enrichment
      of sulfhydryl-containing peptides with thiopropyl sepharose beads. The
      derivatization process includes: (1) acetylation with acetic anhydride to block
      all primary amines, (2) reduction of nitrotyrosine to aminotyrosine, (3)
      derivatization of aminotyrosine with N-Succinimidyl S-Acetylthioacetate (SATA),
      and (4) deprotection of S-acetyl on SATA to form free sulfhydryl groups. The high
      specificity of this method is demonstrated by the contrasting percentage of
      nitrotyrosine-derivatized peptides in the identified tandem mass spectra between
      enriched and unenriched samples. Global analysis of unenriched in vitro nitrated
      human histone H1.2, bovine serum albumin (BSA), and mouse brain homogenate
      samples had 9%, 9%, and 5.9% of identified nitrotyrosine-containing peptides,
      while the enriched samples had 91% , 62%, and 35%, respectively. Duplicate LC
      MS/MS analyses of the enriched mouse brain homogenate identified 150 unique
      nitrated peptides covering 102 proteins with an estimated 3.3% false discovery
      rate.

PMID- 17497907
TI  - The alterations of mouse plasma proteins during septic development.
AB  - A fundamental issue for sepsis therapy is to control the development of
      inflammation at an early stage. With cecal ligation and puncture (CLP) surgery,
      the mouse model has clearly shown the septic signs triggered by chronic insult.
      To monitor the plasma proteomic responses to sepsis, the mouse blood was
      collected at intervals after sham and CLP surgery followed by the sample
      treatment to remove high abundance serum albumin. The treated mouse plasma
      proteins were well resolved by two-dimensional electrophoresis (2-DE). The image
      analysis revealed that these 2-DE spots observed from the sham and the CLP
      samples 4 h after surgery were comparable, whereas more than 30 different spots
      appeared on the 2-DE gels between the sham and CLP mouse plasma 24 h after
      surgery, indicating that some plasma proteins responded to the inflammatory
      development. These differential spots were verified by MALDI-TOF/TOF MS,
      resulting in 13 unique sepsis-responsive proteins. More importantly, most of them
      exhibited multiple spots as difference on the 2-DE gels. Furthermore, these
      isospots were incubated with PNGase F to eliminate N-linked oligosaccharides on
      proteins and then evaluated by Western blot as well as mass spectrometry. The
      results of PNGase F digestion suggested that most sepsis-associated proteins
      remained in N-glycosylation status but changed their N-glycans during septic
      development.

PMID- 17497909
TI  - Proteomic analyses of zebra finch optic tectum and comparative histochemistry.
AB  - Proteomic analyses of zebra finch (Taeniopygia guttata) optic tectum resulted in
      identification of 176 proteins. In the Swissprot database, only 52 proteins were
      identified as bird homologs and only 71 proteins were identified in songbird
      transcriptome databases, reflecting a lack of completeness in the T. guttata
      genomic sequence. Analysis in Kyoto encyclopedia of genes and genome (KEGG)
      pathway database found that identified proteins most frequently belong to
      glucose, pyruvate, glyoxylate, dicarboxylate, alanine, and aspartate metabolism
      pathways. A number of identified proteins have been previously reported to exist
      in the avian optic tectum. The immunohistochemical localization of selected
      proteins showed their distribution in similar laminae of the owl (Tyto alba) and
      chicken (Gallus gallus) tectum. Immunohistochemical analysis of identified
      proteins can provide clues about cell types and circuit layout of the avian optic
      tectum in general. As the optic tectum of nonmammals is homologous to the
      superior colliculus of mammals, the analysis of the tectal and collicular
      proteome may provide clues about conserved cell and circuit layout, circuit
      function, and evolution.

PMID- 17497908
TI  - Proteomic profiling of the silkworm skeletal muscle proteins during larval-pupal
      metamorphosis.
AB  - The silkworm is a typical holometabolous insect going through drastic
      morphological changes upon metamorphosis from larvae to pupae. Comprehensive
      studies focusing on the changes help elucidate understanding of a biogenic
      mechanism. Here, we report the initial profile of the intersegmental muscle (ISM)
      proteins of the silkworm during larval-pupal metamorphosis. In total, 258 protein
      spots were resolved by two-dimensional gel electrophoresis (2-DE). Fifty-seven
      larval proteins were identified, where 3 proteins were exclusively detected in
      larval samples. Fifty-four other proteins were common in pupal samples. Of these,
      12 proteins belonging to the contractile apparatus, metabolism, regulation, and
      signal transduction were altered in their contents during the metamorphosis from
      larvae to pupae. Three pupa-defective proteins were identified as isoforms of
      troponin I, followed by an immunoblotting validation. This data will be helpful
      in understanding the biochemistry of an insect ISM.

PMID- 17497910
TI  - Electrostatic versus nonelectrostatic effects in DNA sequence discrimination by
      divalent ions Mg2+ and Mn2+.
AB  - Mg2+ and Mn2+ ions are critical to the functioning of phosphoryl transfer
      enzymes, such as restriction endonucleases. Although these ions play similar
      roles in the chemical steps, they govern substrate specificity via modulating
      sequence discrimination by up to a factor of 10(5) with Mg2+ and only up to a
      factor of 10 with Mn2+. To explain whether such diversity originates in
      fundamental differences in the electronic structures of the nucleobase-hydrated
      metal ion complexes, structures and interaction energies were determined at the
      density functional (DFT) and second-order Moller-Plesset (MP2) levels of theory.
      Although both metal ions favor identical binding sites, Mn2+ complexes exhibit
      greater distortions from the ideal octahedral geometry and larger variability
      than the corresponding Mg2+ systems. In inner-shell complexes, with direct
      contact between the metal and the nucleobase, Mg2+ is preferred over Mn2+ in the
      gas phase, due primarily to nonelectrostatic effects. The interaction energies of
      the two metal ions are more similar in the outer-shell complexes, likely due to
      reduced charge transfer between the hydrated metal ion and the base moieties.
      Inclusion of solvation effects can amplify the relative nucleobase preferences of
      Mg2+ and Mn2+, indicating that bulk hydration modulates the balance between
      electrostatic and nonelectrostatic terms. In most cases, the base substitutions
      in solution are facilitated more by Mn2+ than by Mg2+. Electrostatic properties
      of the environment were demonstrated to have a major influence on the nucleobase
      preferences of the two metal ions. Overall, quantum chemical calculations suggest
      that the contrasting selectivity of Mg2+ and Mn2+ cofactors toward nucleobases
      derives from the larger flexibility of the Mn2+ complexes accompanied by the
      excessive polarization and charge-transfer effects as well as less favorable
      solvation.

PMID- 17497911
TI  - Tunable filtering of chemical signals in a simple nanoscale reaction-diffusion
      network.
AB  - We study numerically the filtering capabilities of a nanoscale network of two
      micrometer-sized containers joined by a nanotube, one of which hosts an enzymatic
      chemical reaction. Spatiotemporal chemical signals of substrate molecules are
      injected into the network. The substrate propagates by diffusion and reacts with
      enzymes distributed in the network prior to the injections. The dimensions of the
      network are tailored in a way that the transport and enzymatic reaction rates are
      comparable in size, a situation in which the overall behavior is highly
      influenced by the geometry and topology of the network. This property is crucial
      for the functionality of the filter developed in here. It is demonstrated that
      input signals can be classified in a crude way using a simple setup (a two
      container network) and that the classification can be tuned by changing the
      geometry of the network (the length of the tube connecting the two containers).
      The filter device we investigate can also be viewed as a primitive chemistry
      based computational element in the sense that the information encoded in the
      signals is processed using chemical reactions. In particular, it is demonstrated
      that the two-container device may filter out signals based on the average
      injection frequency.

PMID- 17497912
TI  - Single-molecule conductance of redox molecules in electrochemical scanning
      tunneling microscopy.
AB  - Experimental data and theoretical notions are presented for 6-[1'-(6-mercapto
      hexyl)-[4,4']bipyridinium]-hexane-1-thiol iodide (6V6) "wired" between a gold
      electrode surface and tip in an in situ scanning tunneling microscopy
      configuration. The viologen group can be used to "gate" charge transport across
      the molecular bridge through control of the electrochemical potential and
      consequently the redox state of the viologen moiety. This gating is theoretically
      considered within the framework of superexchange and coherent two-step notions
      for charge transport. It is shown here that the absence of a maximum in the
      Itunneling versus electrode potential relationship can be fitted by a "soft"
      gating concept. This arises from large configurational fluctuations of the
      molecular bridge linked to the gold contacts by flexible chains. This view is
      incorporated in a formalism that is well-suited for data analysis and reproduces
      in all important respects the 6V6 data for physically sound values of the
      appropriate parameters. This study demonstrates that fluctuations of isolated
      configurationally "soft" molecules can dominate charge transport patterns and
      that theoretical frameworks for compact monolayers may not be directly applied
      under such circumstances.

PMID- 17497913
TI  - Orientation-resolving pulsed electron dipolar high-field EPR spectroscopy on
      disordered solids: I. Structure of spin-correlated radical pairs in bacterial
      photosynthetic reaction centers.
AB  - Distance and relative orientation of functional groups within protein domains and
      their changes during chemical reactions determine the efficiency of biological
      processes. In this work on disordered solid-state electron-transfer proteins, it
      is demonstrated that the combination of pulsed high-field EPR spectroscopy at the
      W band (95 GHz, 3.4 T) with its extensions to PELDOR (pulsed electron-electron
      double resonance) and RIDME (relaxation-induced dipolar modulation enhancement)
      offers a powerful tool for obtaining not only information on the electronic
      structure of the redox partners but also on the three-dimensional structure of
      radical-pair systems with large interspin distances (up to about 5 nm).
      Strategies are discussed both in terms of data collection and data analysis to
      extract unique solutions for the full radical-pair structure with only a minimum
      of additional independent structural information. By this novel approach, the
      three-dimensional structure of laser-flash-induced transient radical pairs
      P(865)(*+)Q(A)(*-) in frozen-solution reaction centers (RCs) from the
      photosynthetic bacterium Rhodobacter (Rb.) sphaeroides is solved. The measured
      positions and relative orientations of the weakly coupled ion radicals P(865)(*+)
      and Q(A)(*-) are compared with those of the precursor cofactors P865 and QA known
      from X-ray crystallography. A small but significant reorientation of the reduced
      ubiquinone QA is revealed and interpreted as being due to the photosynthetic
      electron transfer. In contrast to the large conformational change of Q(B)(*-)
      upon light illumination of the RCs, the small light-induced reorientation of
      Q(A)(*-) had escaped previous attempts to detect structural changes of
      photosynthetic cofactors upon charge separation. Although small, they still may
      be of functional importance for optimizing the electronic coupling of the redox
      partners in bacterial photosynthesis both for the charge-separation and charge
      recombination processes.

PMID- 17497914
TI  - Cooperative hydrogen bonds of macromolecules. 3. A model study of the proximity
      effect.
AB  - Experimental and theoretical evidence for the proximity effect as a basic
      mechanism of the hydrogen bond cooperativity was obtained in a model system.
      Hydrogen bond (HB) interaction between poly(4-vinylpyridine) (PVP) and selected
      acids as HB donors was studied using PFG NMR self-diffusion measurements, 1H NMR
      longitudinal relaxation and quantum-mechanical DFT calculations. Bivalent HB
      donors, such as glutaric (GA) and adipic acid (AA), were compared to univalent
      donors 4-chlorobutyric acid, 4-acetylbutyric acid and 5-chlorovaleric acid. PFG
      NMR established substantially larger HB equilibrium constants for AA and, in
      particular, GA than for univalent donors, thus indicating cooperativity of COOH
      groups in bivalent donors. According to the values of these constants, the
      fraction of the transiently bound GA and AA molecules, which are bound by two
      hydrogen bonds, is 0.70 and 0.63, respectively. This result, which means
      substantial cooperativity in particular in GA, was then independently verified by
      a relaxation study comparing longitudinal relaxation rates of univalent and
      bivalent donors. Analysis of relaxation led to the same probabilities that HB of
      one COOH group of a bivalent donor will be accompanied by HB of another COOH
      group of the same molecule, namely 0.70 for GA and 0.63 for AA. Such
      cooperativity must be due to the proximity effect, i.e., the lowering of the
      entropy demand of the next binding by the motional restriction imposed by the
      already existing bonds. This conclusion is in excellent agreement with DFT
      calculations on the interaction of GA with a model vinylpyridine dimer, which
      predict preference of double binding of the same GA molecule over that of two GA
      molecules and show that this preference is due to a substantially lower entropy
      demand.

PMID- 17497915
TI  - Comparative study of the effect of tail corrections on surface tension determined
      by molecular simulation.
AB  - We report results from a comparative study of the influence of tail corrections
      on the surface tension of the Lennard-Jones fluid. We find that cutoff
      independent surface tensions can be obtained by applying a set of tail
      corrections recently introduced by Janecek at each step of an interfacial Monte
      Carlo (MC) or molecular dynamics (MD) simulation. The effect of tail corrections
      on an alternative methodology for calculating surface tension, the combination of
      finite-size scaling and grand-canonical transition-matrix Monte Carlo (FSS/GC
      TMMC), was also investigated. Using this indirect method, surface tensions were
      calculated with standard (bulk-fluid) tail corrections and lattice sums, the
      latter usually considered more accurate but computationally more intensive than
      the former. With standard tail corrections, we find that the surface tension
      decreases with increasing cutoff distance, reaching a limiting value
      corresponding to the maximum cutoff possible, namely half the simulation box
      length. In contrast, surface tension values obtained with the lattice summation
      were cutoff-independent. More importantly, these values were equivalent to those
      surface tension values obtained using standard tail corrections and a cutoff
      distance of half the box length. We also find that the surface tension values
      obtained here are in agreement with those found in the literature. Last, we find
      that surface tension values obtained by MD and FSS/GC-TMMC are in decent
      agreement so long as the appropriate tail correction schemes are used, and that
      the relative uncertainties in the surface tensions calculated by MD are generally
      an order of magnitude greater than those calculated by FSS/GC-TMMC. However, the
      time required by MD on a single central processing unit is less than that
      required by FSS/GC-TMMC.

PMID- 17497916
TI  - Computational investigation on the desensitizing mechanism of graphite in
      explosives versus mechanical stimuli: compression and glide.
AB  - A desensitizing mechanism of graphite in explosives versus mechanical stimuli was
      investigated using computational methods including density function theory and
      molecular dynamics. Dependences of energy change versus compression ratio and
      internal stress versus compression at absolute zero degree showed that the most
      possible compression was along the c-axis of graphite crystal. The result of
      molecular dynamics at room temperature indicated that the slide can readily occur
      between neighbor layers, but the distance between them can hardly change. The
      calculated potential energy of the slide of graphite within 0-0.19 kJ/cm3 is much
      larger than the potential energy of compression of common explosives to the
      extent of no detonation, for example, HMX, 0-0.046 kJ/cm3. It implied that the
      kinetic energy induced by mechanical stimuli can easily and partly convert into
      the potential energy of the slide and prevent explosives from forming hot spots.
      This should be the root reason for graphite used as a desensitizer in explosives.

PMID- 17497917
TI  - Pressure dependence of the contact angle.
AB  - When a liquid and its vapor contact a smooth, homogeneous surface, Gibbsian
      thermodynamics indicates that the contact angle depends on the pressure at the
      three-phase line of an isothermal system. When a recently proposed adsorption
      isotherm for a solid-vapor interface is combined with the equilibrium conditions
      and the system is assumed to be in a cylinder where the liquid-vapor interface
      can be approximated as spherical, the contact-angle-pressure relation can be made
      explicit. It indicates that a range of contact angles can be observed on a smooth
      homogeneous surface by changing the pressure at the three-phase line, but it also
      indicates that the adsorption at the solid-liquid interface is negative, and
      leads to the prediction that the contact angle increases with pressure. The
      predicted dependence of the contact angle on pressure is investigated
      experimentally in a system that has an independent mechanism for determining when
      thermodynamic equilibrium is reached. The predictions are in agreement with the
      measurements. The results provide a possible explanation for contact angle
      hysteresis.

PMID- 17497918
TI  - H and other transfers in enzymes and in solution: theory and computations, a
      unified view. 2. Applications to experiment and computations.
AB  - Equations obtained in part I for the free-energy barrier to one-step enzymatic
      reactions between bound reactants are discussed. The rate is expressed in terms
      of lambdao (protein reorganization energy), DeltaG(o) (standard free energy of
      reaction of the H-transfer step), bond breaking/bond forming term, w (work
      terms), and H-transmission property. Two alternative approximations for the
      coupling of the bond breaking/bond forming and protein are distinguished
      experimentally in favorable cases by the DeltaG(o) where the maximum deuterium
      kinetic isotope effect occurs. Plots of log rate versus DeltaG(o) and properties
      such as DeltaS* and DeltaS(o) are discussed. The weak or zero T-dependence of the
      kinetic isotope effect for wild-type enzymes operating under physiological
      conditions is interpreted in terms of vanishing (or isotopically insensitive) w
      plus transfer from the lowest H-state. Static and dynamic protein flexibility is
      discussed. While the many correlations accessible for electron transfers are not
      available for H-transfers in enzymes, a combination of experiment, computation,
      and analytical approaches can assist in evaluating the utility of the present
      equations and in suggesting further experiments and computations. A protein
      reorganization energy lambdao is obtained in the literature from the extended
      valence bond formalism where diabatic electronic states are used. A method is
      suggested for extracting it when instead a bond distance difference coordinate is
      used. The results may provide a bridge between the two approaches.

PMID- 17497919
TI  - Solvation structure of Li+ in concentrated LiPF6-propylene carbonate solutions.
AB  - Time-of-flight neutron diffraction measurements were carried out for 6Li/7Li
      isotopically substituted 10 mol % LiPF6-propylene carbonate-d6 (PC-d6) solutions,
      in order to obtain structural information on the first solvation shell of Li+.
      Structural parameters concerning the nearest neighbor Li+...PC and Li+...PF6-
      interactions were determined through least-squares fitting analysis of the
      observed difference function, DeltaLi(Q). It has been revealed that the first
      solvation shell of Li+ consists in average of 4.5(1) PC molecules with an
      intermolecular Li+...O(PC) distance of 2.04(1) A. The angle Li+...O=C bond angle
      has been determined to be 138(2) degrees.

PMID- 17497920
TI  - Grafting of oligosaccharides onto synthetic polymer colloids.
AB  - A new method to form colloidally stable oligosaccharide-grafted synthetic polymer
      particles has been developed. The oligosaccharides, of weight-average degree of
      polymerization approximately 38, were obtained by enzymatic debranching of
      amylopectin. Through the use of a cerium(IV)-based redox initiation process,
      oligosaccharide chains are grafted onto a synthetic polymer colloid comprising
      electrostatically stabilized poly(methyl methacrylate) or polystyrene latex
      particles swollen with methyl methacrylate monomer. Ce(IV) creates a radical
      species on these oligosaccharides, which then propagates, initially with aqueous
      phase monomer, then with the methyl methacrylate monomer inside the particles.
      Ultracentrifugation, NMR, and total starch analyses together prove that the
      grafting process has occurred, with at least 7.7 wt % starch grafted and a
      grafting efficiency of 33%. The surfactant used in latex preparation was removed
      by dialysis, resulting in particles colloidally stabilized with only linear
      starch as a steric stabilizer. The debranched starch that comprises these
      oligosaccharides is found to be a remarkably effective colloidal stabilizer,
      albeit at low electrolyte concentration, stabilizing particles with very sparse
      surface coverage.

PMID- 17497921
TI  - PEG-SS-PPS: reduction-sensitive disulfide block copolymer vesicles for
      intracellular drug delivery.
AB  - Under appropriate conditions, block copolymeric macroamphiphiles will self
      assemble in water to form vesicles, referred to as polymersomes. We report here
      polymersomes that can protect biomolecules in the extracellular environment, are
      taken up by endocytosis, and then suddenly burst within the early endosome,
      releasing their contents prior to exposure to the harsh conditions encountered
      after lysosomal fusion. Specifically, block copolymers of the hydrophile
      poly(ethylene glycol) (PEG) and the hydrophobe poly(propylene sulfide) (PPS) were
      synthesized with an intervening disulfide, PEG17-SS-PPS30. Polymersomes formed
      from this block copolymer were demonstrated to disrupt in the presence of
      intracellular concentrations of cysteine. In cellular experiments, uptake,
      disruption, and release were observed within 10 min of exposure to cells, well
      within the time frame of the early endosome of endolysosomal processing. This
      system may be useful in cytoplasmic delivery of biomolecular drugs such as
      peptides, proteins, oligonucleotides, and DNA.

PMID- 17497922
TI  - Chiral molecular switches based on binaphthalene molecules with anthracene
      moieties: CD signal due to interchromophoric exciton coupling and modulation of
      the CD spectrum.
AB  - By coupling the features of binaphthalene and anthracene, new binaphthalenes with
      two anthracene moieties were designed and synthesized, aiming at developing
      chiral molecular switches. A strong CD signal with negative sign due to the
      interchromophoric exciton coupling was observed for (S)-1 with -(CH2)2 as the
      linker. This new CD signal became weak and the sign reversed by changing the
      linker to -(CH2)3 in (S)-2 and -(CH2)6 in (S)-3. For (S)-4 with -(CH2)11 as the
      linker, no such CD signal was detected. Photodimerization of two anthracene
      moieties in these binaphthalene molecules can occur. The results show that the CD
      spectra of (S)-1, (S)-2, (S)-3, and (R)-1 can be reversibly modulated by
      alternating UV light irradiation and heating. Therefore, chiral molecular
      switches based on new binaphthalenes with two anthracene moieties are achieved.

PMID- 17497923
TI  - Formal synthesis of (+)-brefeldin A: application of a zinc-mediated ring
      expansion reaction.
AB  - An efficient formal synthesis of (+)-brefeldin A was accomplished through a
      synthetic approach that relied upon three keys steps. The five-membered ring was
      generated in a stereocontrolled fashion through application of a tandem conjugate
      addition-intramolecular cyclization method developed by Toru. Ring-closing
      metathesis provided access to a twelve-membered beta-keto lactone, which was ring
      expanded to the alpha,beta-unsaturated-gamma-keto lactone through a zinc
      carbenoid-mediated reaction. Conversion of this lactone to (+)-brefeldin A has
      been reported previously.

PMID- 17497924
TI  - A divergent synthesis of functionalized unsaturated delta-lactones from alpha
      alkenoyl-alpha-carboxyl ketene dithioacetals.
AB  - A divergent synthesis of functionalized unsaturated delta-lactones 2, 3, 4, and 5
      has been developed starting from the readily available alpha-alkenoyl-alpha
      carboxyl ketene dithioacetals 1 in high to excellent yields under mild reaction
      conditions. Thus, 6-substituted 3-(1,3-dithiolan/dithian-2-ylidene)-3H-pyran
      2(6H)-ones 2, obtained from a consecutive reduction with NaBH4 and acidic workup
      of 1 via a novel vinylogous Pummerer cyclization, can be further transformed into
      alpha-pyranones 3, 4, and 5 upon a sequential isomerization catalyzed by
      triethylamine (to give 3), followed by dethioacetalization (to give 4) or a
      formylation with Vilsmeier reagent (to give 5).

PMID- 17497925
TI  - Selective dimerization of arylalkynes to (E)-1,4-diaryl enynes catalyzed by the
      [Ru(p-cymene)Cl(2)](2)/acetic acid system under phosphine-free conditions.
AB  - The commercially available di-mu-chlorobis[(p-cymene)chlororuthenium(II)] complex
      catalyzes the dimerization of aromatic alkynes in acetic acid at room temperature
      to form the corresponding (E)-1,4-diarylbut-1-ene-3-yne derivatives, with high
      stereoselectivity. The procedure does not require the use of additives and can be
      carried out in the presence of water or aprotic cosolvents, under homogeneous
      conditions.

PMID- 17497926
TI  - Theoretical study of chemo-, regio-, and stereoselectivity in 1,3-dipolar
      cycloadditions of nitrones and nitrile oxides to free and Pt-bound bifunctional
      dipolarophiles.
AB  - 1,3-Dipolar cycloadditions of nitrones RCH=N(CH3)O and the nitrile oxide CH3CNO
      to the bifunctional cyanoalkynes NC-CCR' and cyanoalkenes E-NCCH=CHR' (R=H, Ph;
      R'=H, Ph)--both free and ligated to PtII and PtIV--were investigated by
      theoretical methods at B3LYP and, for some reactions, CCSD(T) and CBS-Q levels of
      theory. Chemo-, regio-, and stereoselectivity of the processes and factors, which
      affect the reactivity and selectivity, were analyzed, and verified trends are
      discussed in details. Coordination of dipolarophiles to PtII and, particularly,
      to PtIV facilitates the CN relative to the CC additions of nitrones due to higher
      activation of the CN group in comparison to the CC group. The bonding of the
      ligands to platinum also favors the meta versus ortho pathways and endo versus
      exo pathways that sometimes lead to a switch of the reaction direction.
      Introduction of Ph groups into the reactant(s) molecules also leads to the
      promotion of the CN versus CC routes, and this effect is especially strong when
      both reactants are Ph-substituted. The substituent effect is accounted for by
      steric repulsions imposed by the Ph groups in transition states (TSs) and by the
      loss of a conjugation in phenylnitrone and phenylcyanoalkene molecules upon the
      TS formation. Solvation inhibits the CN and meta-CC additions and, hence,
      generally favors the CC versus CN pathway, the ortho versus meta pathway, and the
      exo versus endo pathway. All reactions except one proceed concertedly via a
      nearly synchronous mechanism for the CN and meta-CC additions to free ligands and
      asynchronous mechanism for the other processes. For the reaction CH2=N(CH3)O +
      PtIV-1, a stepwise route is realized.

PMID- 17497927
TI  - A facile synthetic method for conversion of chlorophyll-a to bacteriochlorophyll
      c.
AB  - A simple synthetic route for converting chlorophyll(Chl)-a to
      bacteriochlorophyll(BChl)-c is described. Methyl bacteriopheophorbide(MBPhe)-d,
      easily obtained from Chl-a, was selectively brominated at the 20-position with
      pyridinium tribromide, and the following Suzuki-coupling with methylboronic acid
      afforded ca. a 4:1 mixture of desired MBPhe-c (20-Me) and debrominated MBPhe-d
      (20-H) in quantitative yield. Separation of MBPhe-c, transesterification of the
      17-propionate group (Me --> farnesyl), and magnesium insertion successfully led
      to naturally occurring BChl-c.

PMID- 17497928
TI  - Resin-bound sulfonyl azides: efficient loading and activation strategy for the
      preparation of the N-acyl sulfonamide linker.
AB  - This paper describes an optimized protocol for the efficient loading of resin
      bound aminoethane sulfonyl azides by either Boc- or Fmoc-protected amino
      thioacids. The resulting N-acyl sulfonamide is a convenient linker for use in Boc
      or Fmoc-based solid-phase peptide synthesis. Activation of the N-acyl
      sulfonamide via a microwave-assisted alkylation procedure and subsequent
      treatment with functionalized nucleophiles yields C-terminally modified peptides
      that can be applied in chemoselective (bio)conjugation or ligation reactions.

PMID- 17497929
TI  - Efficient synthesis of taurine and structurally diverse substituted taurines from
      aziridines.
AB  - Taurine and substituted taurines were synthesized efficiently from aziridines via
      ring-opening reaction with thioacetic acid, oxidation with performic acid, and
      hydrolysis in hydrochloric acid. The current method shows more benefit in
      purification and efficiency in the preparation of taurine and structurally
      diverse 2-substituted, 2,2-disubstituted, and 1,2-, 2,2-, and 2,N-alkylene
      taurines.

PMID- 17497930
TI  - A traceless approach for the solid-phase parallel synthesis of trisubstituted
      oxindoles.

PMID- 17497931
TI  - Advances in solid-phase cycloadditions for heterocyclic synthesis.

PMID- 17497932
TI  - An efficient method for solution-phase parallel synthesis of 2-quinoxalinol salen
      Schiff-base ligands.
AB  - A solution-phase parallel method for the synthesis of 2-quinoxalinol salen
      ligands was designed and optimized. The synthesis begins with commercially
      available 1,5-difluoro-2, 4-dinitrobenzene (DFDNB) and employs a sequence of five
      straightforward and high-yielding reaction steps. Simple laboratory techniques
      with low sensitivity to water or air for solution-phase parallel reactions were
      coupled with convenient workup and purification procedures to give high-purity
      and yield a small ligand library of 20 compounds. The final step, a Schiff-base
      condensation of an aldehyde with the diaminoquinoxaline results in a new category
      of ligands for metal coordination or of potential bioactivity, based on the
      skeleton 2,2'-(1E,1'E)-(quinoxaline-6,7-diylbis(azan-1-yl-1-ylidene))bis(methan-1
      yl-1-ylidene)diphenol. The approach described here is easily adaptable for
      parallel synthesis of a larger library.

PMID- 17497933
TI  - Mechanism and thermodynamics of binding of the polypyrimidine tract binding
      protein to RNA.
AB  - The polypyrimidine tract binding protein (PTB) is involved in many physiological
      processes, including alternative splicing, internal ribosomal entry side (IRES)
      mediated initiation of translation, and polyadenylation, as well as in ensuring
      mRNA stability. However, the role of PTB in these processes is not fully
      understood, and this has motivated us to undertake a computational study of the
      protein. PTB RNA binding domains (RBDs) 3 and 4 and their complexes with
      oligopyrimidine RNAs were simulated using the GROMOS simulation software using
      the GROMOS 45A4 force field. First, the stability and fluctuations of the
      tertiary fold and of the secondary structural elements in individual domains, the
      combined RBD34 domain, and their complexes with RNA were studied. Second, the
      simulation results were validated against the experimental NMR NOE data. The
      analysis of hydrogen bonding patterns, salt bridge networks, and stacking
      interactions of the RNA to the binding pockets of the protein domains showed that
      binding is not sequence-specific and that many RNA fragments can bind to them
      successfully. Further calculations of the relative free energy of binding for
      different polypyrimidine sequences were carried out using the thermodynamic
      integration (TI) and single-step perturbation (SSP) methods. It is was not
      possible to calculate the relative free energies with high accuracy, but the
      obtained results do give qualitative insights into PTB's affinity for different
      RNA sequences. Furthermore, the low-energy conformations of the complexes that
      were found provided additional information about the mechanism of binding.

PMID- 17497934
TI  - Biochemical and crystallographic analysis of substrate binding and conformational
      changes in acetyl-CoA synthetase.
AB  - The adenylate-forming enzymes, including acyl-CoA synthetases, the adenylation
      domains of non-ribosomal peptide synthetases (NRPS), and firefly luciferase,
      perform two half-reactions in a ping-pong mechanism. We have proposed a domain
      alternation mechanism for these enzymes whereby, upon completion of the initial
      adenylation reaction, the C-terminal domain of these enzymes undergoes a 140
      degrees rotation to perform the second thioester-forming half-reaction.
      Structural and kinetic data of mutant enzymes support this hypothesis. We present
      here mutations to Salmonella enterica acetyl-CoA synthetase (Acs) and test the
      ability of the enzymes to catalyze the complete reaction and the adenylation half
      reaction. Substitution of Lys609 with alanine results in an enzyme that is unable
      to catalyze the adenylate reaction, while the Gly524 to leucine substitution is
      unable to catalyze the complete reaction yet catalyzes the adenylation half
      reaction with activity comparable to the wild-type enzyme. The positions of these
      two residues, which are located on the mobile C-terminal domain, strongly support
      the domain alternation hypothesis. We also present steady-state kinetic data of
      putative substrate-binding residues and demonstrate that no single residue plays
      a dominant role in dictating CoA binding. We have also created two mutations in
      the active site to alter the acyl substrate specificity. Finally, the
      crystallographic structures of wild-type Acs and mutants R194A, R584A, R584E,
      K609A, and V386A are presented to support the biochemical analysis.

PMID- 17497937
TI  - Substitutions in the N-glycan core as regulators of biorecognition: the case of
      core-fucose and bisecting GlcNAc moieties.
AB  - Core fucosylation and the bisecting N-acetylglucosamine residue are prominent
      natural substitutions of the N-glycan core. To address the issue of whether these
      two substituents can modulate ligand properties of complex-type biantennary N
      glycans, we performed chemoenzymatic synthesis of the respective galactosylated
      and alpha2,3/6-sialylated N-glycans. Neoglycoproteins were then produced to
      determine these glycans' reactivities with sugar receptors in solid-phase assays
      and with tumor cells in vitro as well as their in vivo biodistribution profiles
      in mice. Slight protein-type-dependent changes were noted in lectin binding,
      including adhesion/growth-regulatory galectins as study objects, when the data
      were related to properties of N-glycans without or with only one core
      substituent. Monitoring binding in vitro revealed cell-type-dependent changes.
      They delimited the ligand activity of this glycan type from that of chains with
      un- and monosubstituted cores. A markedly prolonged serum half-life was conferred
      to the neoglycoprotein by the galactose-terminated N-glycan, which together with
      increased organ retention of all three neoglycoproteins underscores the
      conspicuous relevance for glycoengineering of pharmaproteins. The predominant
      presentation of the two branches in the disubstituted N-glycan as extended
      (alpha1,3-antenna) and backfolded (alpha1,6-antenna) forms, revealed by molecular
      dynamics simulations, can underlie the measured characteristics. These results
      obtained by a combined strategy further support the concept of viewing N-glycan
      core substitutions as non-random additions which exert a modulatory role on
      ligand properties. Moreover, our data inspire us to devise new, non-natural
      modifications to realize the full potential of glycoengineering for diagnostic
      and therapeutic purposes.

PMID- 17497935
TI  - A comparative NMR study of the polypeptide backbone dynamics of hemoglobin in the
      deoxy and carbonmonoxy forms.
AB  - Model-free-based NMR dynamics studies have been undertaken for polypeptide
      backbone amide N-H bond vectors for both the deoxy and carbonmonoxy forms of
      chain-specific, isotopically (15N and 2H) labeled tetrameric hemoglobin (Hb)
      using 15N-relaxation parameters [longitudinal relaxation rate (R1), transverse
      relaxation rate (R2), and heteronuclear nuclear Overhauser effect (NOE)] measured
      at two temperatures (29 and 34 degrees C) and two magnetic field strengths (11.7
      and 14.1 T). In both deoxy and carbonmonoxy forms of human normal adult
      hemoglobin (Hb A), the amide N-H bonds of most amino acid residues are rigid on
      the fast time scale (nanosecond to picosecond), except for the loop regions and
      certain helix-helix connections. Although rigid in deoxy-Hb A, beta146His has
      been found to be free from restriction of its backbone motions in the CO form,
      presumably due to the rupture of its hydrogen bond/salt bridge network. We now
      have direct dynamics evidence for this structural transition of Hb in solution.
      While remarkably flexible in the deoxy state, alpha31Arg and beta123Thr,
      neighbors in the intradimer (alpha1beta1) interface, exhibit stiffening upon CO
      binding. These findings imply a role for alpha31Arg and beta123Thr in the
      intradimer communication but contradict the results from X-ray crystallography.
      We have also found that there is considerable flexibility in the intradimer
      (alpha1beta1) interface (i.e., B, G, and H helices and the GH corner) and
      possible involvement of several amino acid residues (e.g., alpha31Arg, beta3Leu,
      beta41Phe, beta123Thr, and beta146His) in the allosteric pathway. Several amino
      acid residues at the intradimer interfaces, such as beta109Val, appear to be
      involved in possible conformational exchange processes. The dynamic picture
      derived from the present study provides new insights into the traditional
      description of the stereochemical mechanism for the cooperative oxygenation of Hb
      A based on X-ray crystallographic results.

PMID- 17497938
TI  - Characterization of an Fe(2+)-dependent archaeal-specific GTP cyclohydrolase,
      MptA, from Methanocaldococcus jannaschii.
AB  - The first step in the biosynthesis of pterins in bacteria and plants is the
      conversion of GTP to 7,8-dihydro-d-neopterin triphosphate catalyzed by GTP
      cyclohydrolase I (GTPCHI). Although GTP has been shown to be a precursor of
      pterins in archaea, homologues of GTPCHI have not been identified in most
      archaeal genomes. Here we report the identification of a new GTP cyclohydrolase
      that converts GTP to 7,8-dihydro-d-neopterin 2',3'-cyclic phosphate, the first
      intermediate in methanopterin biosynthesis in methanogenic archaea. The enzyme
      from Methanocaldococcus jannaschii is designated MptA to indicate that it
      catalyzes the first step in the biosynthesis of methanopterin. MptA is the
      archetype of a new class of GTP cyclohydrolases that catalyzes a series of
      reactions most similar to that seen with GTPCHI but unique in that the cyclic
      phosphate is the product. MptA was found to require Fe2+ for activity. Mutation
      of conserved histidine residues H200N, H293N, and H295N, expected to be involved
      in Fe2+ binding, resulted in reduced enzymatic activity but no reduction in the
      amount of bound iron.

PMID- 17497936
TI  - X-ray crystal structures reveal two activated states for RhoC.
AB  - RhoC is a member of the Rho family of Ras-related (small) GTPases and shares
      significant sequence similarity with the founding member of the family, RhoA.
      However, despite their similarity, RhoA and RhoC exhibit different binding
      preferences for effector proteins and give rise to distinct cellular outcomes,
      with RhoC being directly implicated in the invasiveness of cancer cells and the
      development of metastasis. While the structural analyses of the signaling-active
      and -inactive states of RhoA have been performed, thus far, the work on RhoC has
      been limited to an X-ray structure for its complex with the effector protein,
      mDia1 (for mammalian Diaphanous 1). Therefore, in order to gain insights into the
      molecular basis for RhoC activation, as well as clues regarding how it mediates
      distinct cellular responses relative to those induced by RhoA, we have undertaken
      a structural comparison of RhoC in its GDP-bound (signaling-inactive) state
      versus its GTP-bound (signaling-active) state as induced by the nonhydrolyzable
      GTP analogues, guanosine 5'-(beta,gamma-iminotriphosphate) (GppNHp) and guanosine
      5'-(3-O-thiotriphosphate) (GTPgammaS). Interestingly, we find that GppNHp-bound
      RhoC only shows differences in its switch II domain, relative to GDP-bound RhoC,
      whereas GTPgammaS-bound RhoC exhibits differences in both its switch I and switch
      II domains. Given that each of the nonhydrolyzable GTP analogues is able to
      promote the binding of RhoC to effector proteins, these results suggest that RhoC
      can undergo at least two conformational transitions during its conversion from a
      signaling-inactive to a signaling-active state, similar to what has recently been
      proposed for the H-Ras and M-Ras proteins. In contrast, the available X-ray
      structures for RhoA suggest that it undergoes only a single conformational
      transition to a signaling-active state. These and other differences regarding the
      changes in the switch domains accompanying the activation of RhoA and RhoC
      provide plausible explanations for the functional specificity exhibited by the
      two GTPases.

PMID- 17497939
TI  - The unusually strong hydrogen bond between the carbonyl of Q(A) and His M219 in
      the Rhodobacter sphaeroides reaction center is not essential for efficient
      electron transfer from Q(A)(-) to Q(B).
AB  - In native reaction centers (RCs) from photosynthetic purple bacteria the primary
      quinone (QA) and the secondary quinone (QB) are interconnected via a specific His
      Fe-His bridge. In Rhodobacter sphaeroides RCs the C4=O carbonyl of QA forms a
      very strong hydrogen bond with the protonated Npi of His M219, and the Ntau of
      this residue is in turn coordinated to the non-heme iron atom. The second
      carbonyl of QA is engaged in a much weaker hydrogen bond with the backbone N-H of
      Ala M260. In previous work, a Trp side chain was introduced by site-directed
      mutagenesis at the M260 position in the RC of Rb. sphaeroides, resulting in a
      complex that is completely devoid of QA and therefore nonfunctional. A
      photochemically competent derivative of the AM260W mutant was isolated that
      contains a Cys side chain at the M260 position (denoted AM260(W-->C)). In the
      present work, the interactions between the carbonyl groups of QA and the protein
      in the AM260(W-->C) suppressor mutant have been characterized by light-induced
      FTIR difference spectroscopy of the photoreduction of QA. The QA-/QA difference
      spectrum demonstrates that the strong interaction between the C4=O carbonyl of QA
      and His M219 is lost in the mutant, and the coupled CO and CC modes of the QA-
      semiquinone are also strongly perturbed. In parallel, a band assigned to the
      perturbation of the C5-Ntau mode of His M219 upon QA- formation in the native RC
      is lacking in the spectrum of the mutant. Furthermore, a positive band between
      2900 and 2400 cm-1 that is related to protons fluctuating within a network of
      highly polarizable hydrogen bonds in the native RC is reduced in amplitude in the
      mutant. On the other hand, the QB-/QB FTIR difference spectrum is essentially the
      same as for the native RC. The kinetics of electron transfer from QA- to QB were
      measured by the flash-induced absorption changes at 780 nm. Compared to native
      RCs the absorption transients are slowed by a factor of about 2 for both the slow
      phase (in the hundreds of microseconds range) and fast phase (microseconds to
      tens of microseconds range) in AM260(W-->C) RCs. We conclude that the unusually
      strong hydrogen bond between the carbonyl of QA and His M219 in the Rb.
      sphaeroides RC is not obligatory for efficient electron transfer from QA- to QB.

PMID- 17497941
TI  - Meeting highlights of the European Respiratory Society annual congress 02-06
      September 2006, Munich, Germany.
AB  - In pulmonary medicine, there are two major international meetings held annually:
      the annual meeting of the American Thoracic Society (ATS), and that of the
      European Respiratory Society (ERS). The 2006 ERS Annual Congress was held in
      Munich, Germany. Both meetings provide an annual forum for scientists and
      clinical investigators from academia, non-university institutions (including
      private practices) and pharmaceutical companies to share information on many
      aspects of pulmonary and critical-care medicine, sleep disorders, pulmonary
      infectious diseases, malignancies of the chest, and numerous aspects of
      diagnostic and interventional procedures in these fields. With > 5000 abstracts
      and ~ 17,000 participants, the 2006 ERS-congress outnumbered even the 2006 ATS
      meeting. Research areas covered all aspects of pulmonary diseases, although this
      year (as in previous years) obstructive pulmonary diseases such as COPD (chronic
      obstructive pulmonary disease) and asthma were clearly the main focus.

PMID- 17497940
TI  - Protein arginine deiminase 4: evidence for a reverse protonation mechanism.
AB  - The presumed role of an overactive protein arginine deiminase 4 (PAD4) in the
      pathophysiology of rheumatoid arthritis (RA) suggests that PAD4 inhibitors could
      be used to treat an underlying cause of RA, potentially offering a mechanism to
      stop further disease progression. Thus, the development of such inhibitors is of
      paramount importance. Toward the goal of developing such inhibitors, we initiated
      efforts to characterize the catalytic mechanism of PAD4 and thereby identify
      important mechanistic features that can be exploited for inhibitor development.
      Herein we report the results of mutagenesis studies as well as our efforts to
      characterize the initial steps of the PAD4 reaction, in particular, the
      protonation status of Cys645 and His471 prior to substrate binding. The results
      indicate that Cys645, the active site nucleophile, exists as the thiolate in the
      active form of the free enzyme. pH studies on PAD4 further suggest that this
      enzyme utilizes a reverse protonation mechanism.

PMID- 17497959
TI  - Normal cellular prion protein is a ligand of selectins: binding requires Le(X)
      but is inhibited by sLe(X).
AB  - The normal PrP(C) (cellular prion protein) contains sLe(X) [sialyl-Le(X) (Lewis
      X)] and Le(X). sLe(X) is a ligand of selectins. To examine whether PrP(C) is a
      ligand of selectins, we generated three human PrP(C)-Ig fusion proteins: one with
      Le(X), one with sLe(X), and the other with neither Le(X) nor sLe(X). Only Le(X)
      PrP(C)-Ig binds E-, L- and P-selectins. Binding is Ca(2+)-dependent and occurs
      with nanomolar affinity. Removal of sialic acid on sLe(X)-PrP(C)-Ig enables the
      fusion protein to bind all selectins. These findings were confirmed with brain
      derived PrP(C). The selectins precipitated PrP(C) in human brain in a Ca(2+)
      dependent manner. Treatment of brain homogenates with neuraminidase increased the
      amounts of PrP(C) precipitated. Therefore the presence of sialic acid prevents
      the binding of PrP(C) in human brain to selectins. Hence, human brain PrP(C)
      interacts with selectins in a manner that is distinct from interactions in
      peripheral tissues. Alternations in these interactions may have pathological
      consequences.

PMID- 17497960
TI  - Increased expression and phosphorylation of focal adhesion kinase correlates with
      dysfunction in the volume-overloaded human heart.
AB  - FAK (focal adhesion kinase) has been shown to mediate the hypertrophic growth of
      the left ventricle. Experimental results also suggest that FAK may contribute to
      the structural and functional deterioration of the chronically overloaded left
      ventricle. In the present study, we postulated that FAK expression and
      phosphorylation may be altered in the volume-overloaded heart in humans. FAK
      expression and phosphorylation at Tyr(397) were detected by Western blotting and
      immunohistochemistry in samples from endomyocardial biopsies from patients with
      MR (mitral regurgitation; n=21) and donor subjects (n=4). Hearts from patients
      with MR had degenerated cardiac myocytes and areas of fibrosis. In this group,
      the myocardial collagen area was increased (18% in MR hearts compared with 3% in
      donor hearts respectively) and correlated negatively with left ventricular
      ejection fraction (r=-0.74; P>0.001). FAK expression and phosphorylation at
      Tyr(397) (a marker of the enzyme activity) were increased in samples from MR
      hearts compared with those from donor hearts (3.1- and 4.9-fold respectively). In
      myocardial samples from donor hearts, anti-FAK staining was almost exclusively
      restricted to cardiac myocytes; however, in myocardial samples from MR hearts,
      staining with the anti-FAK antibody was found to occur in myocytes and the
      interstitium. There was a positive correlation between collagen and the
      interstitial areas stained with the anti-FAK antibody (r=0.76; P>0.001). Anti-FAK
      and anti-vimentin staining of the interstitial areas of samples from MR hearts
      were extensively superimposed, indicating that most of the interstitial FAK was
      located in fibroblasts. In conclusion, FAK expression and phosphorylation are
      increased and may contribute to the underlying structural and functional
      abnormalities in the volume-overloaded heart in humans.

PMID- 17497961
TI  - Structurally reduced monosaccharide transporters in an evolutionarily conserved
      red alga.
AB  - The unicellular red alga Galdieria sulphuraria is a facultative heterotrophic
      member of the Cyanidiaceae, a group of evolutionary highly conserved
      extremophilic red algae. Uptake of various sugars and polyols is accomplished by
      a large number of distinct plasma membrane transporters. We have cloned three
      transporters [GsSPT1 (G. sulphuraria sugar and polyol transporter 1), GsSPT2 and
      GsSPT4], followed their transcriptional regulation and assayed their transport
      capacities in the heterologous yeast system. SPT1 is a conserved type of
      sugar/H(+) symporter with 12 predicted transmembrane-spanning domains, whereas
      SPT2 and SPT4 represent monosaccharide transporters, characterized by only nine
      hydrophobic domains. Surprisingly, all three proteins are functional plasma
      membrane transporters, as demonstrated by genetic complementation of a sugar
      uptake-deficient yeast mutant. Substrate specificities were broad and largely
      redundant, except for glucose, which was only taken up by SPT1. Comparison of
      SPT1 and truncated SPT1(Delta1-3) indicated that the N-terminus of the protein is
      not required for sugar transport or substrate recognition. However, its deletion
      affected substrate affinity as well as maximal transport velocity and released
      the pH dependency of sugar uptake. In line with these results, uptake by SPT2 and
      SPT4 was active but not pH-dependent, making a H(+) symport mechanism unlikely
      for the truncated proteins. We postulate SPT2 and SPT4 as functional plasma
      membrane transporters in G. sulphuraria. Most likely, they originated from genes
      encoding active monosaccharide/H(+) symporters with 12 transmembrane-spanning
      domains.

PMID- 17497962
TI  - Relevant risk for women with BRCA1 and BRCA2 mutations.

PMID- 17497963
TI  - Beware the Buruli ulcer.

PMID- 17497964
TI  - The surgical workload already within the hospital.

PMID- 17497965
TI  - Infrared spectroscopy and pancreatitis.

PMID- 17497966
TI  - Cancer risks for Australian women with a BRCA1 or a BRCA2 mutation.
AB  - One of the primary purposes of genetic testing for mutations in the BRCA1 and
      BRCA2 genes in patients with familial breast/ovarian cancer has been to provide
      accurate advice to at-risk relatives. The provision of such advice has been
      hampered by a lack of appropriate data regarding the cancer risks. Chen and
      colleagues recently provided precise estimates of the relative risks of breast
      and ovarian cancer in almost 2000 kindreds with such mutations ascertained
      through familial cancer clinics across USA. The baseline incidence of breast
      cancer is lower in Australia than in North America. The relative risks derived
      from the study have been combined with Australian baseline incidence data to
      estimate the absolute short-term and long-term risks of breast and ovarian
      cancers for Australian carriers of different ages. The results are presented as a
      series of graphs that may be useful in counselling an unaffected carrier of a
      specified age. It is of note that the incidence of breast cancer in carriers is
      high in premenopausal women, but approaches the population incidence in
      postmenopausal women. Conversely, the incidence of ovarian cancer continues to
      increase from the age of 40 years. Among carriers of BRCA1 or BRCA2 mutations,
      the cumulative lifetime risk of developing breast cancer is 50-60% and the
      equivalent risk of ovarian cancer is 20-40%. An unaffected carrier aged 60 years
      is at greater risk of developing ovarian cancer than breast cancer. These
      observations have important implications for genetic counselling and decisions
      regarding prophylactic surgery.

PMID- 17497967
TI  - Slow-transit constipation: evaluation and treatment.
AB  - Slow-transit constipation is characterized by delay in transit of stool through
      the colon, caused by either myopathy or neuropathy. The severity of constipation
      is highly variable, but may be severe enough to result in complete cessation of
      spontaneous bowel motions. Diagnostic tests to assess colonic transit include
      radiopaque marker or radioisotope studies, and intraluminal tests (colonic and
      small bowel manometry). Most patients with functional constipation respond to
      laxatives, but a small proportion are resistant to this treatment. In some
      patients biofeedback is helpful although the mechanism by which this works is
      still uncertain. Other patients are resistant to all conservative modes of
      therapy and require surgical intervention. Extensive clinical and physiological
      preoperative assessment of patients with slow colonic transit is essential before
      considering surgery, including an assessment of small bowel motility and
      identification of coexistent obstructed defecation. The psychological state of
      the patient should always be taken into account. When surgery is indicated,
      subtotal colectomy and ileorectal anastomosis is the operation of choice.
      Segmental colonic resection has been reported in a few patients, but methods of
      identifying the affected segment need to be developed further. Less invasive and
      reversible surgical options include laparoscopic ileostomy, antegrade colonic
      enema and sacral nerve stimulation.

PMID- 17497968
TI  - Homocysteine and abdominal aortic aneurysms.
AB  - There is evidence to suggest that increased levels of homocysteine play a
      significant role in vascular disease. It has been suggested that lowering
      homocysteine levels by dietary folate supplementation may reduce the risk of
      stroke and coronary heart disease. It is plausible that homocysteine may also
      play a role in the pathogenesis of abdominal aortic aneurysms (AAA) and that
      patients with this disease may benefit from folate supplementation. Our objective
      was to review the published work with regard to the role of homocysteine in the
      pathogenesis of AAA. Searches were carried out in published work in English with
      the keywords 'abdominal aortic aneurysm' and 'homocysteine'. There is evidence
      from in vitro and animal model studies that activation of metalloproteinases by
      homocysteine can influence aortic wall structure. Several case-control studies
      report an association between increased levels of homocysteine and the presence
      of an AAA. There are conflicting genotypic data concerning the association
      between methylenetetrahydrofolate reductase gene variants and AAA. Although there
      is evidence for an association between homocysteine and AAA, it is not strong
      enough to conclude that it plays a causal role in the pathogenesis of AAA.
      Further research is needed, given the potential benefit that simple vitamin
      supplementation may have for patients with AAA.

PMID- 17497969
TI  - Drain clamping in knee arthroplasty, a randomized controlled trial.
AB  - BACKGROUND: The purpose of this study was to determine whether repeated clamping
      of a suction drainage system will result in less external blood loss, blood
      transfusion and no increase in complications compared to a routine continuous
      suction drainage system. This was a randomized prospective study on patients
      undergoing total knee arthroplasty. METHODS: Group A patients' drains were left
      clamped for all but 5 min (or 100 mL drainage) every 2 h for the first 6 h, then
      at 12-h and 24-h periods, when the drains were removed. Group B patients had
      continuous suction drainage. The amount of external blood loss, transfusion
      requirements and complications were compared between the two groups. The study
      group comprised 66 patients. RESULTS: The mean external blood loss in the clamped
      drain group was 296.67 mL (standard deviation 160.28 mL) with a mean drain in
      situ time of 32 h, significantly less (P < 0.05) than the continuous drain group
      that had a mean external blood loss of 796 mL (standard deviation 250.34 mL) with
      a mean drain in situ time of 34 h. There was no difference in the requirements
      for transfusion between the two groups. CONCLUSION: We conclude that clamping
      drains intermittently in hybrid total knee arthroplasty results in significantly
      less external blood loss with no change in morbidity or mortality. This study was
      a level 1 therapeutic study (i.e. with level of evidence randomized control trial
      with a significant difference).

PMID- 17497970
TI  - Discrepancies in Gleason scoring of prostate biopsies and radical prostatectomy
      specimens and the effects of multiple needle biopsies on scoring accuracy. A
      regional experience in Tamworth, Australia.
AB  - BACKGROUND: The aim of this study was to review the discrepancies in Gleason
      scores (GS) of prostate biopsies and radical prostatectomy specimens and the
      effects of multiple-needle biopsies on scoring accuracy. METHODS: One hundred
      patients who had undergone consecutive radical prostatectomies (RP) between
      January 2004 and May 2006 were reviewed retrospectively. Patient information
      including age, prebiopsy prostate-specific antigen levels, biopsy GS, RP GS and
      pathology details were recorded and compared. RESULTS: The concordance rate of
      biopsy GS and RP GS was found to be at 43%, with 46% of biopsy specimens being
      undergraded. Eleven per cent of the specimens were overgraded. The accuracy was
      fairly similar when specimens were reported by the same or different
      pathologists, at 42 and 44%, respectively. The accuracy of biopsy GS improved
      with increasing number of biopsies taken. CONCLUSION: There are significant
      discrepancies in Gleason scoring of biopsy and RP specimens, with a concordance
      rate of 43% and undergrading rate of 46%. Increasing the number of biopsies helps
      improve scoring accuracy. Clinicians and patients need to be mindful when
      deciding cancer treatment options, in view of these discrepancies.

PMID- 17497971
TI  - Surgical outcome of superficial and deep Castleman disease.
AB  - BACKGROUND: Castleman disease is a rare lymphoproliferative disease of low
      malignant potential occurring in two forms, unicentric and multicentric. Surgery,
      chemotherapy, immunotherapy and radiation therapy have all been used to manage
      the disease. In this study, we evaluate whether the site of the lesions, that is,
      superficial or deep, influences the surgical outcome. METHODS: We retrospectively
      reviewed the records of 20 patients operated on for Castleman disease from 1994
      to 2003, of whom 11 patients had superficial disease and 9 had deep lesions. The
      end-points of this study were survival and recurrence. RESULTS: Of the 20
      patients, 19 had unicentric (cervical in 8, mediastinal in 5, retroperitoneal in
      2, axillary in 2, hepatic in 1, and mesenteric in 1) and 1 had multicentric
      Castleman disease. Among 19 patients who had complete resection (18 with
      unicentric and 1 with multicentric disease), there has been no evidence of
      recurrence. CONCLUSION: Whether Castleman disease is superficial or deep has no
      effect on surgical outcome as long as resection is complete.

PMID- 17497972
TI  - Spirometric changes after pleural decortication in young adults.
AB  - BACKGROUND: The collection of pleural fluid and thickened pleura restrict the
      movement and expansion of lung. The main treatment strategy is lung decortication
      for the thickened pleura. The aim of this study was to investigate lung functions
      before and after pleural decortication in young adults. METHODS: A total of 63
      patients with thickened pleura were retrospectively evaluated. Before the
      operation, patients with tuberculosis (n = 36) were treated with anti
      tuberculosis therapy for 3-6 months. Patients with non-tuberculosis causes (n =
      27) had been treated with broad-spectrum antibiotics. Forced expiratory volume in
      1 s (FEV1, %), forced vital capacity (%) and vital capacity (litre) were measured
      before and after decortication. RESULTS: Spirometric parameters FEV1 (68.1 +/-
      16.7 vs 71.01 +/- 14.4), forced vital capacity (67.6 +/- 16.4 vs 71.3 +/- 14.4)
      and vital capacity (2.6 +/- 0.6 vs 2.8 +/- 0.7) significantly improved after the
      operation (P +/- 0.01). Spirometric changes were not significantly different
      between tuberculosis and non-tuberculosis groups. CONCLUSION: Pleural
      decortication may improve the lung restoration in patients with thickened pleura
      and also improve lung functions significantly in young adults.

PMID- 17497973
TI  - Usefulness of infrared spectroscopy in diagnosis of acute pancreatitis.
AB  - BACKGROUND: The lack of a gold standard for the diagnosis of acute pancreatitis
      remains a problem. Our aim was to evaluate whether infrared spectroscopy of serum
      can establish the diagnosis of acute pancreatitis. METHODS: Sixty-four patients
      with acute pancreatitis, 112 patients with non-pancreatic acute abdomen and 40
      healthy subjects were studied. In addition to serum infrared spectral analysis,
      serum concentrations of amylase and lipase were measured on admission. RESULTS:
      Infrared spectroscopy based on serum absorption patterns in the range 800-1000 nm
      successfully distinguished acute pancreatitis from acute abdominal disorders of
      extrapancreatic origin and from control specimens. The sensitivity, specificity
      and positive and negative predictive values of infrared spectroscopy on admission
      were 91, 91, 85, and 94%, respectively. Within 24 h of onset of symptoms,
      infrared spectroscopy, lipase and amylase showed similar areas under the ROC
      curves for infrared spectra of serum (0.93), lipase (0.96) and amylase (0.91).
      CONCLUSIONS: The successful classification of infrared spectra in patients with
      acute pancreatitis implies that the pathophysiology of disease alters the
      composition of the specimen in a characteristic fashion--in this case the serum
      make-up reflects the presence of acute pancreatitis.

PMID- 17497974
TI  - Vascular surgery consults: a significant workload.
AB  - BACKGROUND: Patients with vascular disease typically suffer from widespread
      atherosclerosis and complex multisystem pathologies. As a result, it may be
      expected that significant portion of a vascular surgeon's inpatient workload is
      derived from consultations from other inpatient specialist units. This aspect of
      the workload of vascular surgeons is poorly documented. METHODS: A prospective
      audit on inpatient vascular consultations was carried out. All vascular
      admissions to the Vascular Surgery unit at the Royal Hobart Hospital as well as
      inpatient referrals by other units over a 6-month period were recorded on a
      database. The data were analysed to evaluate the number of inpatient
      consultations, the reason for the consultation and its outcome. RESULTS: Most
      inpatient referrals were derived from internal medicine (32%), renal,
      endocrinology and plastic surgery units (26, 13 and 9%, respectively). Sixty-four
      per cent of all referrals required intervention with most of these patients
      having been referred from renal and endocrinology units. CONCLUSION: In our
      experience, 50% of the vascular surgeon's inpatient workload is derived from
      inpatient referrals. Sixty-four per cent of referrals required some form of
      vascular intervention. This aspect of vascular workload is significant and has
      not been previously documented. It is time-consuming and also resource consuming
      and this needs to be taken into consideration when allocating theatre resources
      and during rostering.

PMID- 17497975
TI  - Gall bladder polyps in sclerosing cholangitis: does the 1-cm rule apply?
AB  - INTRODUCTION: Polyps of the gall bladder (PLG) are common findings in
      radiological investigations of the gall bladder and most are benign although
      carcinoma of the gall bladder can arise in PLG. In the general population PLG
      less than 1 cm in diameter are thought to have a low risk of malignancy and can
      be cautiously observed. METHODS: All patients undergoing surgical resection for
      gall bladder cancer were entered into a prospective database. Four patients with
      primary sclerosing cholangitis (PSC) presenting with gall bladder cancer in a PLG
      are studied. RESULTS: Four patients (two men; median age 46.5 years, range 37-71
      years) presented with PLG and known histories of PSC. All patients were shown to
      have PLG of size between 7 mm x 8 mm and 25 mm x 14 mm on imaging with no
      radiological evidence of carcinoma. Tumour markers carcinoembryonic antigen and
      CA19-9 were within the normal range in all patients. All patients were managed
      with cholecystectomy. Two patients with T1 tumours remain alive and well at 2 and
      4 years post-cholecystectomy. Of the remaining two patients with T2 tumours, one
      underwent re-resection of the liver bed and portal lymph nodes and remains alive
      and well at 12 months. The remaining patient developed an abdominal wall
      recurrence 12 months after cholecystectomy. She has also undergone resection with
      postoperative radiation therapy and remains well after 12 months of clinical
      follow up. CONCLUSION: Gall bladder polyps, which are common and are usually
      benign in the general population, are often malignant in PSC. Regardless of size,
      any PLG in a patient with PSC should be considered for cholecystectomy.

PMID- 17497976
TI  - Increasing numbers of admissions to the adult burns service at the Royal Adelaide
      Hospital 2001-2004.
AB  - BACKGROUND: The purpose of the study was to illustrate the increasing trend in
      the number of adult burns patients admitted to the Royal Adelaide Hospital and
      attempt to explain it and to describe the burn patients admitted to the Royal
      Adelaide Hospital in terms of age, sex, origin, cause and burn size, particularly
      since the increasing trend began, in an effort to identify a particular group or
      burn cause, which may make up a large proportion of the increasing numbers.
      METHODS: A retrospective review of 1548 acute burn-injured patients using
      information from the burns unit database between 1996 and 2004 was carried out.
      RESULTS: Of 1841 total admissions, 1548 were admitted for acute burn injury.
      There has been an increase in the number of admissions since 2001 amounting to
      approximately 20% per annum. The cumulative rise in total admissions 2000-2004 is
      107% where the increase in acute burn admission in the same period is 82%. There
      appears to be no difference whether the patient is from a rural or a metropolitan
      area. Burns of <10% total body surface area constitute most of the increase and
      are mainly flame and scald injuries. Chemical and contact burns are
      proportionately increasing. CONCLUSION: The increase in acute admissions is
      mainly due to the increasing presentation of smaller burns to the unit. The
      statewide rural burn education programme and media exposure following the 2002
      Bali bombings may have contributed to the increase in acute admissions.

PMID- 17497977
TI  - Benign nodular goitre presenting as acute airway obstruction.
AB  - BACKGROUND: Although rare in non-endemic areas, benign nodular goitre may cause
      acute airway obstruction and the clinical management of this condition remains a
      challenge. METHODS: From 1996 to 2005, a total of 1115 patients underwent thyroid
      surgery at our institution and of these, 7 patients were identified to have a
      benign nodular goitre leading to acute airway obstruction. They were
      retrospectively reviewed with reference to the aetiology, presentation,
      perioperative management and postoperative outcome. RESULTS: All seven patients
      were elderly women with a history of symptomatic goitre and concomitant medical
      problems. Five patients required emergency tracheal intubation, whereas two
      patients underwent urgent tracheostomy. Total thyroidectomy was successfully
      carried out for all patients and there was no hospital death. Perioperative
      complications included three patients with pneumonia, two with renal failure and
      one with perforated duodenal ulcer. Surgically related complications included
      transient recurrent nerve palsy in one patient and transient hypocalcaemia in
      four. After a median follow up of 22 months (range, 4-53 months), two patients
      died of cerebrovascular accident. CONCLUSION: Prompt airway protection followed
      by total thyroidectomy within the same hospital admission should be recommended
      and can be associated with favourable outcome.

PMID- 17497978
TI  - Mycobacterial soft tissue infections in North Queensland.
AB  - BACKGROUND: Mycobacterial soft tissue infections are a heterogeneous group of
      infections that usually require a variety of therapeutic methods for cure. North
      Queensland has an environment, which predisposes to several such infections. The
      aim of this study was to assess the incidence and epidemiology of mycobacterial
      soft tissue infections in North Queensland and to review surgical and non
      surgical interventions in these conditions. METHODS: This study was a
      retrospective review of all patients with a proven mycobacterial soft tissue
      infection, seen between 1997 and 2005 in a tertiary referral centre in North
      Queensland. RESULTS: In total, 34 patients were identified. The most common
      causative organisms were Mycobacterium fortuitum (44%), M. ulcerans (17.6%) and
      M. abscessus (11.8%). The risk factors identified were the male sex, lower-limb
      involvement and preceding trauma including surgery. Twenty-four (70.6%) patients
      had surgical excision or debridement with a variety of adjuvant antimicrobial
      therapies. There were eight (23.5%) local recurrences. CONCLUSION: The optimal
      management of soft tissue mycobacterial infections includes early microbiological
      identification based on tissue biopsy, appropriate combination antimicrobial
      therapy and early wide surgical excision where appropriate. North Queensland has
      a unique environment, which may predispose to these infections. An awareness of
      this is essential to surgical practice in the region.

PMID- 17497979
TI  - Treatment of duodenal adenomas with endoscopic argon plasma coagulation.
AB  - BACKGROUND: Surgical resection has been the standard treatment for duodenal
      adenomas. It has a high associated morbidity rate and a significant recurrence
      rate. The aim of this study was to evaluate endoscopic treatment of these lesions
      with argon plasma coagulation. METHODS: We retrospectively identified patients
      with non-ampullary duodenal adenomas without a polyposis syndrome and who were
      treated endoscopically between 1st January 1999 and 31st December 2003. Their
      management, follow up and outcomes were reviewed. RESULTS: Fifteen patients were
      included, with mean age 72 years (range 46-85 years). All were treated with at
      least one session of argon plasma coagulation. Initially, 13 adenomas were
      macroscopically cleared. Of these, eight (61%) had no recurrence during mean
      follow up of 40 months (26-68 months). The mean time to recurrence was 14 months
      (6-30 months). Eradication was possible a second time in four of five recurrent
      adenomas. There was one complication, of haemorrhage, from 37 sessions of argon
      plasma coagulation. No patient developed duodenal adenocarcinoma during the study
      period. CONCLUSION: Argon plasma coagulation may be safe and effective for the
      treatment of duodenal adenomas, but further research is required. Progression of
      adenomas is slow and perhaps no treatment is required.

PMID- 17497980
TI  - Sensation recovery improved by great auricular nerve preservation in
      parotidectomy: a prospective double-blind study.
AB  - BACKGROUND: The great auricular nerve (GAN) is frequently sacrificed during
      parotidectomy and causes sensory disturbance of the auricle. Our study is to
      investigate whether GAN preservation can improve the sensory recovery. METHODS:
      Patients undergoing superficial or total conservative parotidectomy for benign
      tumours were recruited consecutively from November 1998 to September 2001.
      Different sensory methods (light touch, two-point discrimination and sharp pain)
      of the auricle were evaluated by a designated physiotherapist preoperatively as
      well as at 1, 3, 6 and 12 months postoperatively. The patients and the
      physiotherapist were blinded to the integrity of the GAN. Long-term subjective
      assessment was also carried out beyond 2 years postoperatively. RESULTS: A total
      of 21 patients were recruited for the study. GAN were preserved in 10 patients.
      The mean follow up was 16 months (12-42 months). There was no difference in sex
      distribution, type of operation and pathology of parotid tumour between the two
      groups. No postoperative mortality occurred and postoperative morbidity did not
      differ between the two groups. Patients with GAN preserved had significantly
      better light touch and sharp pain recovery at 1 year postoperatively. Subjective
      assessment of sensory dysfunction also favoured GAN preservation. CONCLUSION:
      Great auricular nerve preservation minimizes the postoperative sensory
      disturbance and should be considered whenever tumour clearance is not
      compromised.

PMID- 17497981
TI  - Nerve stimulation in thyroid surgery: is it really useful?
AB  - BACKGROUND: Monitoring of the recurrent laryngeal nerve (RLN) has been claimed in
      some studies to reduce rates of nerve injury during thyroid surgery compared with
      anatomical dissection and visual identification of the RLN alone, whereas other
      studies have found no benefit. Continuous monitoring with endotracheal electrodes
      is expensive whereas discontinuous monitoring by laryngeal palpation with nerve
      stimulation is a simple and inexpensive technique. This study aimed to assess the
      value of nerve stimulation with laryngeal palpation as a means of identifying and
      assessing the function of the RLN and external branch of the superior laryngeal
      nerve (EBSLN) during thyroid surgery. METHODS: This was a prospective case series
      comprising 50 consecutive patients undergoing total thyroidectomy providing 100
      RLN and 100 EBSLN for examination. All patients underwent preoperative and
      postoperative vocal cord and voice assessment by an independent ear, nose and
      throat surgeon, laryngeal examination at extubation and all were asked to
      complete a postoperative dysphagia score sheet. Dysphagia scores in the study
      group were compared with a control group (n = 20) undergoing total thyroidectomy
      without nerve stimulation. RESULTS: One hundred of 100 (100%) RLN were located
      without the use of the nerve stimulator. A negative twitch response occurred in
      seven (7%) RLN stimulated (two bilateral, three unilateral). Postoperative
      testing, however, only showed one true unilateral RLN palsy postoperatively (1%),
      which recovered in 7 weeks giving six false-positive and one true-positive
      results. Eighty-six of 100 (86%) EBSLN were located without the nerve stimulator.
      Thirteen of 100 (13%) EBSLN could not be identified and 1 of 100 (1%) was located
      with the use of the nerve stimulator. Fourteen per cent of EBSLN showed no
      cricothyroid twitch on EBSLN stimulation. Postoperative vocal function in these
      patients was normal. There were no instances of equipment malfunction. Dysphagia
      scores did not differ significantly between the study and control groups.
      CONCLUSION: Use of a nerve stimulator did not aid in anatomical dissection of the
      RLN and was useful in identifying only one EBSLN. Discontinuous nerve monitoring
      by stimulation during total thyroidectomy confers no obvious benefit for the
      experienced surgeon in nerve identification, functional testing or injury
      prevention.

PMID- 17497982
TI  - Sphincter-preserving operations without defunctioning stoma.
AB  - Sphincter-preserving operations have increasingly been carried out during the
      last few decades; nevertheless, temporary defunctioning stoma is still being
      frequently used for low colorectal anastomosis (LCRA) with staplers and hand-sewn
      coloanal anastomosis (CAA). From 1994 to 2003, 131 consecutive patients with
      rectal cancer with tumours within 7 cm from the anal verge underwent LCRA or CAA
      without defunctioning stoma. Anastomotic complications and treatment were
      compared between the groups. The median follow up was 31.4 months. Complications
      related to anastomosis were 10.7% for LCRA with 7.1% of anastomotic leakage (two
      men and two women) and 13.3% for CAA with 4.0% of anastomotic leakage (three
      men). Treatments for leakage included colostomy (three LCRA), CAA construction
      (one LCRA) and conservative treatment (three CAA). Twenty eight percent of CAA
      received preoperative radiation therapy, and the anastomic leakage developed in
      14% of them. Anastomotic leakage and its treatment with CAA are different from
      those in LCRA, and CAA can safely be used without defunctioning stoma during
      sphincter-preserving operation for low-lying rectal cancer.

PMID- 17497983
TI  - Influence of surgical technique on axillary seroma formation: a randomized study.
AB  - The aim of this study was to evaluate the influence of surgical technique in the
      form of electrocautery and suction drains on seroma formation following surgery
      for breast cancer. A prospective randomized study was carried out. One hundred
      and sixty patients with breast cancer who underwent surgery were allocated to
      four arms using a 2 x 2 factorial design. This method enabled us to evaluate the
      independent effect of two different causative factors on the incidence of
      postoperative seroma formation using a single dataset with limited numbers. The
      main outcome measure was postoperative seroma formation defined as a
      postoperative axillary collection requiring more than one aspiration after
      removal of the drain. The incidence of seroma in our institution is 90%.
      Incidence of postoperative seroma was 88.3% if electrocautery was used, which
      reduced to 82.2% if surgery was carried out using scissors for dissection and
      ligatures for haemostasis (P = 0.358). There was no influence on the incidence of
      seroma formation whether suction drain (84.6%) or corrugated drains (86.1%) were
      used (P = 0.822). The use of electrocautery in axillary dissection does not
      adversely affect postoperative seroma formation after surgery for breast cancer.
      The use of different drainage techniques has no bearing on the postoperative
      seroma formation. The surgical technique has no influence on the rate of seroma
      formation after surgery for breast cancer.

PMID- 17497988
TI  - Local anaesthetic reduces the pain of drain tube removal.

PMID- 17497990
TI  - Assessing the effectiveness of a mammography screening service.

PMID- 17497991
TI  - Successful repair of aortobronchial fistula using circulatory arrest.

PMID- 17497992
TI  - Iatrogenic oesophageal perforation with necrotizing mediastinitis: surgical
      management following delayed presentation.

PMID- 17497993
TI  - Occupation and carpal tunnel syndrome.

PMID- 17497994
TI  - Primary Kaposi's sarcoma of the appendix: a rare cause of appendicitis.

PMID- 17497995
TI  - Kikuchi's lymphadenitis: cervical lymphadenopathy suggestive of acute lymphoma.

PMID- 17497996
TI  - Double filtration plasmapheresis can decrease factor XIII Activity.
AB  - Factor XIII (FXIII) produces cross-linkages among fibrin molecules within fibrin
      clots. Its deficiency is related with bleeding diathesis or retardation of wound
      healing. We report the possibility that intense double filtration plasmapheresis
      (DFPP) is associated with decreased FXIII activity. Five patients with various
      primary diagnoses were treated with DFPP and their FXIII activity was measured.
      Coagulation test results remained almost normal, but FXIII activities declined to
      less than 20% of their initial value before starting DFPP and 10% after DFPP in
      most cases. The cases that received intense DFPP therapy exhibited profoundly
      decreased FXIII activity. The clinical course demonstrated that DFPP caused the
      FXIII decrease. Fortunately, with careful observation, none of the patients
      experienced fatal bleeding. Only one case required fresh frozen plasma and an
      open hemostatic procedure because of prolonged postoperative bleeding. In
      general, DFPP most efficiently removes substances with the following
      characteristics: adequate molecular weight; long half-life; and small
      extravascular distribution volume. The FXIII properties meet all these
      characteristics. Consequently, we should devote much attention to FXIII activity
      during DFPP because it cannot be estimated from the usual coagulation tests.
      Patients who receive DFPP therapy, especially intensified therapy, should have
      FXIII measured during the course of therapy. Results show that DFPP can decrease
      FXIII activity. For this reason we recommend the measurement of FXIII when
      patients receive intense DFPP therapy with albumin replacement.

PMID- 17497997
TI  - Effects of HELP therapy on acute ischemic stroke and vascular endothelial cell
      function.
AB  - To evaluate the therapeutic effects of the HELP system (heparin-induced
      extracorporeal low-density lipoprotein-apolipoprotein(a)-fibrinogen
      precipitation) in patients with acute ischemic stroke and probe into its possible
      mechanism, 10 patients with acute ischemic stroke were included in this study and
      received the HELP therapy in addition to low molecular weight dextran, salvia
      miltiorrhiza and aspirin. Matched with gender, age, European Stroke Scale (ESS)
      and fibrinogen, 20 patients with cerebral infarction treated with low molecular
      heparin were chosen as controls during the same period. We compared the efficacy
      and prognosis between the two groups. In order to clarify the effects of HELP
      treatment on endothelial function, human umbilical vein endothelial cells (HUVEC)
      were cultured with the serum of pre- and post-HELP therapy and control patients,
      then endothelial permeability and biomarkers of endothelial dysfunction or
      activation in the supernatant of incubated HUVEC, such as soluble thrombomodulin
      (sTM), soluble intracellular adhesion molecule-1 (sICAM-1) and monocyte
      chemoattractant protein-1 (MCP-1), were tested. Twenty-one days after treatment,
      ESS scores in the HELP group (70.4 +/- 23.06) were higher than those in control
      group (60.7 +/- 18.94), but there was no statistical significance (P > 0.05). In
      the HELP group, total efficacy rate reached 60% with ESS score (6 cases of
      recovery and efficacy, 4 cases of inefficacy), while it was 40% in control group
      (8 cases of recovery and efficacy, 12 cases of inefficacy), but unfortunately
      there was no significant difference between both groups using the chi(2)-test (P
      > 0.05). Interestingly, with the activities of daily living (ADL) score, the
      efficacy rate in the HELP group (60%) was markedly higher than that in the
      control group (20%) (P < 0.05). Furthermore, Pearson correlation analysis showed
      that the therapeutic window (the time from the patient's onset to receiving the
      therapy) was correlated to final ADL scores (P = 0.044) and the mean therapeutic
      window was 14.08 +/- 3.41 h in patients who achieved efficacy criteria. After
      therapy, no difference was found in hemorheology, fibrinogen, blood lipid,
      oxidized low-density lipoprotein (oxLDL) or C-reactive protein (CRP) in the
      control group, while there was a significant decrease in the HELP group
      immediately after treatment (P < 0.01). But the hospital stay time was similar
      between the HELP group and the controls (23.11 +/- 10.65 vs. 21.53 +/- 8.73 days;
      P > 0.05) and 21 days later, the dimension of the largest cross-sectioned
      infarction area by CT scan did not significantly change for the two groups' of
      patients (P > 0.05). When cultured with the patient's serum after HELP therapy,
      the concentration of sTM, sICAM-1, and MCP-1 in the supernatant of cultured HUVEC
      remained unchanged at 24 h (P > 0.05), while it was remarkably higher when HUVEC
      was cultured with the serum of the controls and patients before HELP therapy (P <
      0.01), except for sTM. The endothelial permeability was also improved after the
      HELP treatment. With the effects of improving hemorheology, decreasing acute
      phase reactive proteins such as CRP and fibrinogen, ameliorating endothelial cell
      function, HELP system may be a novel therapy for acute ischemic stroke.

PMID- 17497998
TI  - Efficacy of granulocyte and monocyte adsorption apheresis for three cases of
      refractory pyoderma gangrenosum.
AB  - Pyoderma gangrenosum presents with chronic skin ulcers and is histologically
      characterized by neutrophil infiltration throughout the dermis. It is also
      occasionally associated with ulcerative colitis, a type of inflammatory bowel
      disease, against which granulocyte and monocyte adsorption apheresis (GCAP) has
      recently shown remarkable efficacy. We performed GCAP on three refractory cases
      of pyoderma gangrenosum with painful bilateral leg ulcers and hereby report the
      results obtained. Patient 1 was a 43-year-old woman with a four-year history of
      recurrent painful skin ulcers treated with prednisolone and cyclosporine. Patient
      2 was a 29-year-old woman who had been suffering from pyoderma gangrenosum with
      severe pain for two weeks, associated with an 11-year history of ulcerative
      colitis treated with prednisolone and salazosulfapyridine. Patient 3 was a 63
      year-old man with a three-year history of recurrent ulcers with pain, suffering
      from rheumatoid arthritis treated with prednisolone and cyclophosphamide. The
      sizes of the lesions were reduced in all three patients following a weekly GCAP
      treatment for 10 or 11 consecutive weeks, and the re-epithelialization of ulcers
      were additionally observed in two patients. The pain disappeared dramatically in
      all three patients following two sessions of GCAP therapy. No adverse effects
      were observed for up to at least eight months after treatment. We therefore
      considered GCAP as one effective alternative to currently existing therapies,
      with regards to refractory cases of pyoderma gangrenosum.

PMID- 17497999
TI  - Prevalence and determinants of hypertension in chronic hemodialysis patients in
      Japan.
AB  - Hypertension is common in chronic hemodialysis (HD) patients. However, its
      prevalence and determinants have not been studied in a large HD population. We
      analyzed the database of the Japanese Society for Dialysis Therapy (JSDT)
      registry, which conducts an annual survey of chronic dialysis patients throughout
      Japan. We compiled those who were on HD three-times per week and aged 20 years
      and over at the end of 2000 (JSDT standard analysis file 001). Hypertension was
      defined as predialysis systolic blood pressure (SBP) > or =140 mm Hg or
      predialysis diastolic blood pressure (DBP) > or =90 mm Hg. Adjusted odds ratios
      (95% confidence interval) for the determinants of hypertension were calculated by
      the multivariate logistic regression analysis. A total of 65 393 people (men,
      60.2%; mean age +/- SD, 60.9 +/- 12.8 years; and mean duration of HD +/- SD, 95.3
      +/- 74.0 months) were studied. Mean +/- SD levels of SBP and DBP were 154.9 +/-
      23.8 mm Hg and 80.5 +/- 13.7 mm Hg before the HD session. Hypertension was noted
      in 77.5% of patients. Prescription of antihypertensive drugs and erythropoietin
      was made to 60.7% and 82.0% of patients, respectively. Both SBP and DBP were
      higher in those who were prescribed antihypertensive drugs (mean, 160.4/81.9 mm
      Hg), than those without drugs (mean, 146.9/78.5 mm Hg) (in both cases P <
      0.0001). Hypertension was positively associated with men (adjusted odds ratio
      (OR), 1.258; 95% confidence interval (CI), 1.188-1.333; P < 0.0001), age (OR,
      1.004; CI, 1.001-1.006; P < 0.01), duration of HD (OR, 0.769; CI, 0.728-0.812; P
      < 0.0001), serum albumin (OR, 1.369; CI, 1.286-1.458; P < 0.0001), and change in
      body weight by dialysis session (DeltaBW) (OR, 1.176; CI, 1.159-1.194; P <
      0.0001), and was negatively associated with Kt/V (OR, 0.600; CI, 0.543-0.664; P <
      0.0001), and hematocrit (OR, 0.964; CI, 0.959-0.970; P < 0.0001). The
      distribution of DeltaBW was normal in shape and in about 22% of patients the
      range was from 4.0% to 4.9%. There was a significant positive relationship
      between the prevalence of hypertension and DeltaBW (R(2) = 0.8549). The higher
      the DeltaBW, the more the prescription rate of antihypertensive drugs increased
      (R(2) = 0.9102). Results showed that the prevalence of hypertension was
      significantly associated with volume excess and serum levels of albumin, calcium,
      and phosphorous in chronic HD patients. Despite the high prescription rate of
      antihypertensive drugs, control of blood pressure remains unsatisfactory.

PMID- 17498000
TI  - AST-120, an oral adsorbent, delays the initiation of dialysis in patients with
      chronic kidney diseases.
AB  - The effects of an oral adsorbent, AST-120, in chronic kidney disease (CKD)
      patients was evaluated by the 24-month dialysis-free rate and 50% dialysis-free
      period. This study retrospectively analyzed 193 patients admitted to the Osaka
      Medical College Hospital between January 1994 and December 2001 because of CKD
      and who later started dialysis. The propensity score on multiple factors was used
      to match two groups of patients (AST-120 group, n = 78; non-AST-120 group, n =
      78). Then, the proportion of patients remaining dialysis-free and the 50%
      dialysis-free period during the 24 months after starting treatment with or
      without AST-120 were analyzed. The impact of AST-120 on the risk of dialysis
      initiation was also determined by multivariate analysis. There were no
      significant differences in the clinical background and laboratory values after
      matching the two groups using the propensity score. The 50% dialysis-free period
      was significantly prolonged in the AST-120 group compared to the non-AST-120
      group for all patients analyzed, as well as for the subgroup with diabetic or non
      diabetic renal disease. When AST-120 treatment was started at a serum creatinine
      level below 3 mg/dL, the dialysis-free period was longer than 24 months in the
      AST-120 group, compared with 16.2 months in the non-AST-120 group. The 24-month
      dialysis-free rate was higher in the AST-120 group in every patient category. The
      risk of dialysis initiation was increased 3.48-fold in patients who were not
      administered AST-120. These results show that AST-120 delays the initiation of
      dialysis in CKD patients. Thus, AST-120 is an effective supplementary therapy to
      prevent the initiation of dialysis in CKD patients.

PMID- 17498001
TI  - Assessment of lower limb ischemia with measurement of skin perfusion pressure in
      patients on hemodialysis.
AB  - Measurement of skin perfusion pressure (SPP) using laser Doppler has become
      available for the assessment of peripheral arterial disease. We studied whether
      measurements of SPP can be used to identify hemodialyzed patients with peripheral
      arterial disease by comparing it with measurements of the ankle brachial pressure
      index (ABI). The ABI at rest and the SPP in the foot were measured in 59 Japanese
      hemodialyzed patients (118 limbs). Twenty-one patients had diabetes mellitus.
      Five had intermittent claudication; however, 20 patients were accompanied by
      other exertional leg symptoms. The SPP could not be measured in three limbs
      because of involuntary movement due to previous stroke or restless leg syndrome.
      The SPP was correlated with the ABI. Depending upon these results of the ABI, the
      114 limbs from which both the ABI and the SPP could measured were divided into
      three groups: (A) ABI > or = 1.3, (B) 0.9 < or = ABI < 1.3, and (C) ABI < 0.9.
      The average SPP of group C was significantly decreased among the three groups.
      All subjects of the three groups were divided into an extra two groups according
      to the presence of diabetes (non-diabetes groups, -I; diabetes groups, -II). The
      average SPP of group B-II was significantly decreased compared with those of
      group B-I. The SPP measurement is a noninvasive, useful screening method for limb
      ischemia that can be applied to exercise tolerance limited patients. The SPP
      measurements are expected to be useful for the evaluation of limb ischemia in
      hemodialyzed patients at risk.

PMID- 17498002
TI  - Effects of 22-oxacalcitriol and calcitriol on PTH secretion and bone mineral
      metabolism in a crossover trial in hemodialysis patients with secondary
      hyperparathyroidism.
AB  - The purpose of this crossover comparison study is to elucidate the differences
      between the effects of a novel calcitriol analog, 22-oxacalcitriol, and
      calcitriol on parathyroid hormone (PTH) and bone mineral metabolism in
      hemodialysis patients with secondary hyperparathyroidism (SHPT). Twenty-three
      patients with moderate to severe SHPT were included in a random 2 x 2 crossover
      trial with two vitamin D analogs (12 weeks for each treatment). Two patients
      withdrew during the run-in period for personal reasons. Serum electrolyte, bone
      metabolic marker, intact PTH (iPTH) and whole PTH (wPTH) levels were measured
      periodically. The primary endpoint measure was a decrease in serum iPTH level,
      and the secondary outcome measures included changes in serum calcium (Ca),
      phosphate (P), and metabolic bone marker levels. Both treatments decreased iPTH
      and wPTH levels by similar degrees. Serum Ca, P, and Ca x P product levels at the
      end of each treatment were comparable and the frequencies of hypercalcemia and
      hyperphosphatemia were also similar during each treatment period. 22
      Oxacalcitriol significantly decreased the levels of bone metabolic markers,
      namely, bone-specific alkaline phosphate, intact osteocalcin, pyridinoline, and
      cross-linked N-telopeptide of type I collagen, after a 12-week treatment. In
      contrast, calcitriol did not change any of the levels of bone metabolic markers.
      The present study showed that 22-oxacalcitriol is equally effective for PTH
      suppression, and Ca and P metabolism. In addition, 22-oxacalcitriol might have
      putative actions on bone remodeling independent of its PTH suppression. Further
      study is necessary to confirm the effects of 22-oxacalcitriol on bone metabolism
      in SHPT.

PMID- 17498003
TI  - Influence of sevelamer on mineral metabolism and hyperparathyroidism in Japanese
      hemodialysis patients.
AB  - In June 2003, sevelamer hydrochloride became widely available in Japan and was
      expected to control hyperphosphatemia in hemodialysis patients without inducing
      hypercalcemia. To evaluate the impact of sevelamer therapy on mineral metabolism,
      we recruited 954 hemodialysis patients from 21 renal units just before the
      general release of sevelamer in Japan. The serum calcium, phosphate, and
      parathyroid hormone levels determined on enrollment were compared with those
      later measured in June 2004. Sevelamer was prescribed for 169 of the 859 patients
      for whom data were available in 2004. The mean calcium level, phosphate level,
      and calcium x phosphate product were all significantly reduced during the 12
      month study period, but the intact parathyroid hormone (iPTH) level did not
      change. As a result, the percentage of patients who achieved a calcium x
      phosphate product of <55 mg(2)/dL(2) was significantly increased, but there were
      no changes in that of patients who achieved the target ranges for phosphate (3.5
      5.5 mg/dL) or iPTH (150-300 pg/mL). Among sevelamer-treated patients, iPTH
      significantly increased, and this change was more marked in the patients with an
      initial iPTH level <150 pg/mL. Sevelamer was useful for reducing the serum
      calcium level and calcium x phosphate product, but hyperphosphatemia and
      hyperparathyroidism were not improved in our study population at 12 months after
      the release of sevelamer. A decrease in the calcium load might result in the
      exacerbation of hyperparathyroidism. However, among patients with relative
      hypoparathyroidism, sevelamer therapy may be beneficial for the prevention of
      adynamic bone disease.

PMID- 17498004
TI  - Iron status and the use of non-steroidal anti-inflammatory drugs in hemodialysis
      patients.
AB  - We examined whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) can
      affect the anemia and iron status of hemodialysis patients. We recruited patients
      from six dialysis centers who had undergone maintenance hemodialysis for at least
      four months. We examined the use of NSAIDs during the past three months based on
      their medical records and assigned the patients to three groups (group A, non
      NSAID group; group B, aspirin group; and group C, non-aspirin NSAID group). Of
      the 446 patients, 95 (21.3%) were treated with aspirin and 103 (23.1%) were
      treated with non-aspirin NSAIDs. The serum iron level and transferrin saturation
      (TSAT) were significantly lower in group C patients than those in group A.
      However, the ratio of the patients who were administrated iron preparations
      during the past three months was significantly higher than that in the other two
      groups. The incidences of positive fecal occult blood tests did not differ
      substantially between the three groups. The ratios of the patients who were
      administrated recombinant human erythropoietin were the same between three
      groups. Using a multiple regression analysis, the administration of non-aspirin
      NSAIDs was identified as an independent factor for the decreased serum iron and
      the decreased TSAT levels. A multiple logistic regression analysis revealed that
      the patients using non-aspirin NSAIDs had an increased the requirement for iron
      preparation therapy (OR 2.03, 95% CI, 1.28-3.22). The use of non-aspirin NSAIDs
      may therefore increase the risk of the iron deficiency in patients undergoing
      hemodialysis.

PMID- 17498005
TI  - Darbepoetin alfa effectively maintains hemoglobin concentrations at extended dose
      intervals relative to intravenous rHuEPO in Japanese dialysis patients.
AB  - Darbepoetin alfa (KRN321) is a novel molecule that stimulates erythropoiesis by
      the same mechanism as endogenous erythropoietin. Due to its three-fold longer
      half-life and greater biological activity than recombinant human erythropoietin
      (rHuEPO), KRN321 maintains an effective hemoglobin (Hb) level at extended dose
      intervals compared with rHuEPO. In this multicenter, open-label study, 513
      dialysis patients maintained on stable rHuEPO therapy were switched to KRN321 at
      extended dose intervals. Those receiving rHuEPO two (n = 144, 28.1%) or three
      times (n = 305, 59.5%) per week were switched to KRN321 once per week, and those
      receiving rHuEPO once per week (n = 64, 12.5%) were switched to KRN321 once every
      two weeks. The doses of KRN321 (10-120 microg) were titrated to maintain Hb
      concentrations at 10-13 g/dL and, if possible, within 11-12 g/dL for up to 52
      weeks. If the Hb concentration remained between 10.5 and 12 g/dL, conversion of
      the dosing frequency from once per week to once every two weeks was allowed.
      Hemoglobin concentrations were maintained regardless of the dosing interval. The
      percentage of patients with Hb values within 11-12 g/dL was 23.6% at week 0,
      41.3% at week 7, 46.1%-51.9% between weeks 11 and 22 and 45.6% at week 52. KRN321
      was well tolerated and the safety profile was consistent with previous trials
      conducted for KRN321. KRN321, when administered at extended dose intervals, is
      well tolerated and effective Hb concentrations are attained in Japanese
      hemodialysis patients.

PMID- 17498006
TI  - A case report of plasmapheresis and cyclophosphamide for steroid-resistant focal
      segmental glomerulosclerosis: recovery of renal function after five months on
      dialysis.
AB  - We describe a patient who presented with nephrotic syndrome and progressive renal
      failure with biopsy findings of focal segmental glomerulosclerosis (FSGS). He
      progressed rapidly to end-stage renal disease (ESRD) and remained hemodialysis
      dependent for five months despite high dose prednisone therapy. Initiation of
      plasmapheresis and low dose oral cyclophosphamide resulted in the prompt return
      of urine output and renal recovery. He remains off dialysis with stable renal
      function (creatinine clearance = 40 mL/min) two years later. This is the first
      report of late rescue from apparent ESRD due to FSGS with combined plasmapheresis
      and low dose oral cyclophosphamide.

PMID- 17498007
TI  - A case report of neonatal onset multisystemic inflammatory disease in Japan
      treated with continuous hemodiafiltration and steroid pulse therapy.
AB  - Neonatal onset multisystem inflammatory disease (NOMID), which is also known as
      chronic infantile neurological cutaneous and articular syndrome, is a rare
      disease that is characterized by the triad of cutaneous rash, chronic meningitis
      and arthropathy. The long-term prognosis is poor, with progressive deafness and
      visual impairment, and worsening of the central nervous system manifestations.
      Some fatal cases have been reported secondary to infection, vasculitis and
      amyloidosis. We recently managed a typical case of NOMID where the combined
      treatment of continuous hemodiafiltration and steroid pulse therapy was
      effective. The patient showed repeated flare ups of fever, arthralgia and
      meningitis accompanied with high levels of cytokines. The effect was temporary,
      but useful in recovery from such a serious condition.

PMID- 17498008
TI  - A case report of acute renal failure and fulminant hepatitis associated with
      edaravone administration in a cerebral infarction patient.
AB  - A 60-year-old male with cerebral infarction was admitted to our hospital and
      treated with edaravone. On day 12 of hospitalization, he suddenly lost
      consciousness and went into shock. Based on the laboratory findings, acute renal
      failure (ARF), fulminant hepatitis, and disseminated intravascular coagulation
      (DIC) were diagnosed. We immediately initiated continuous hemodiafiltration for
      three days and performed three sessions of plasma exchange. Following this, a
      gradual improvement was observed in the patient's general condition and
      laboratory values. On day 17 of hospitalization, intermittent hemodialysis (HD)
      was initiated. On day 20 of hospitalization, his renal function started to
      improve with an increase in urine volume. HD was successfully discontinued on the
      same day. Although the drug lymphocyte stimulation test for edaravone was
      negative, edaravone-induced fulminant hepatitis was suggested based on liver
      biopsy findings. We present a case of ARF, fulminant hepatitis, and DIC due to
      edaravone administration that was successfully treated with blood purification
      techniques. Since the use of edaravone treatment is expected to increase in the
      future, it is essential that clinicians consider the potential adverse effects of
      this treatment. It is suggested that blood purification is effective in inducing
      remission in patients with complications due to edaravone treatment.

PMID- 17498011
TI  - Caring for children with chronic pain: ethical considerations.

PMID- 17498009
TI  - Is the timing of thallium injection in relation to hemodialysis treatments
      important?

PMID- 17498012
TI  - Anesthesia in HIV-infected children.
AB  - In 2005, it was estimated that 2.3 million children below 15 years of age were
      living with human immunodeficiency virus (HIV)/AIDS and 570,000 children below 15
      years died. Maternal-infant or vertical transmission is the most common mode of
      HIV infection in children. As transplacental passage of maternal anti-HIV
      antibodies, diagnosis of HIV infection in young infants relies on virologic
      assays. Infants older than 18 months of age can be diagnosed by serology alone.
      Pediatric HIV infections are classified according to Center for Disease Control
      and Prevention 1994 revised classification system. The understanding of viral
      pathogenesis, the development of highly active antiretroviral therapy, and the
      ability to quantitate viral burden have led to significant reduction in disease
      progression and morbidity in HIV-infected children. As survival improves, these
      children will require anesthesia care and pain treatment during the course of
      their illness. Considerations for the anesthesiologist include: possible
      involvement of multiple organ systems, adverse reactions and drug interactions of
      antiretroviral agents and adequate infection control to prevent HIV transmission
      in hospital and other infections to the immunocompromised patients. Finally, care
      should be taken not to violate confidentiality.

PMID- 17498013
TI  - The national pediatric epidural audit.
AB  - BACKGROUND: This paper describes a prospective audit of children receiving
      epidural infusion analgesia (EIA) in Great Britain and Ireland. The aim was to
      quantify the risks associated with this technique. METHODS: In order to obtain
      sufficient data on the number of pediatric epidurals performed and the incidence
      of unwanted events, a decision was taken, at an Annual Meeting of Great Britain
      and Ireland Paediatric Pain Services, to establish a national audit of EIA
      practice in these centers. Each site sent a monthly return of the numbers of EIA
      performed to the coordinating center. If an incident occurred then the referring
      site completed a more detailed form and the child was followed up for 1 year if
      possible. Incidents were graded by severity 13, serious to minor. These data were
      collected over the 5-year period (2001-2005). RESULTS: (i) Ninety six incidents
      were reported in 10 633 epidurals performed. (ii) Fifty six were associated with
      the insertion or maintenance of EIA; most were of low severity (1 : 189). (iii)
      Five incidents were graded as 1 (serious) (approximately 1 : 2000). (iv) Nine
      incidents were graded as 2 (approximately 1 : 1100). (v) Only one child has
      residual effects from a grade 1 incident 12 months after surgery (approximately 1
      : 10 000). (vi) Forty incidents were also reported that were felt to be
      associated with the use of EIA; 33 of these incidents were the development of
      pressures sores. Four incidents of compartment syndrome were reported, in each of
      these cases the presence of EIA did not mask the condition. CONCLUSIONS: Epidural
      infusion analgesia in children does have risks associated with the technique. The
      occurrence of compartment syndrome does not appear to be masked by the presence
      of working EIA. As a result of this audit we can now provide parents with better
      information, thereby improving the process of informed consent.

PMID- 17498014
TI  - The effect of videotaped preoperative information on parental anxiety during
      anesthesia induction for elective pediatric procedures.
AB  - BACKGROUND: The purpose of this study was to determine whether audiovisual
      information, describing the process of undergoing and recovering from anesthesia,
      could reduce anxiety levels in parents before their child's induction of
      anesthesia. METHODS: One hundred and eleven parents were recruited into this
      study. Of these 56 were randomized to a control group and 55 to an intervention
      group. All parents completed the Amsterdam Preoperative Anxiety and Information
      Scale (APAIS) questionnaires on admission to hospital on the day of surgery and
      then again just before accompanying their child to the anesthetic room. In
      addition to the normal preoperative preparation, parents randomized into the
      study group watched a short 8-min information video after completing the first
      questionnaire. The video illustrated the events and procedures surrounding a
      child's admission to hospital for day-case surgery, including the induction of
      anesthesia. RESULTS: The results were analyzed using repeated measures of anova.
      There was a statistically significant reduction in anxiety and desire for
      information in the intervention group compared with the control group (P < 0.05).
      CONCLUSIONS: The reduction in anxiety in the intervention group indicates that
      preoperative information videos are an effective method of reducing anxiety in
      parents. Furthermore, the reduction in need for information score in the
      intervention group indicates that preoperative videos may be a useful tool for
      providing parents with information.

PMID- 17498015
TI  - Cardiac rhythm and left ventricular function of infants at 1 MAC sevoflurane and
      halothane.
AB  - BACKGROUND: The implementation of sevoflurane in pediatric anesthesia practice
      led to a decrease in the incidence of cardiac arrest previously reported with
      halothane. Nevertheless, the effects of sevoflurane on cardiac rhythm and
      function have not been systematically investigated in infants. Thus, we compared
      cardiac rhythm and left ventricular function at 1 MAC sevoflurane and halothane
      anesthesia and investigated the potential benefit effect of atropine. METHODS:
      Twenty infants ASA physical status I or II were randomly assigned to have
      anesthesia induced with either sevoflurane (up to 5%) or halothane (up to 1.5%).
      After insertion of an i.v. line, anesthesia was maintained at 1 MAC sevoflurane
      (group S) or 1 MAC halothane (group H) with infants breathing spontaneously in
      100% oxygen. Cardiac output and contractility were measured by transthoracic
      echocardiography. Three sets of hemodynamic parameters were averaged prior to and
      after administration of 20 microg x kg(-1) of i.v. atropine. RESULTS: Infants
      breathing spontaneously 1 MAC halothane or 1 MAC sevoflurane were found to have
      comparable hemodynamic parameters. After atropine administration, heart rate and
      cardiac index (CI) increased significantly in both groups (19.6 +/- 7.6% in group
      H and 21.3 +/- 13.1% in group S, 18.6 +/- 8.8% in group H and 17.7 +/- 12% in
      group S respectively). Moreover, atropine induced an increase in left ventricular
      shortening fraction with no difference between groups. In contrast, only infants
      in group S presented a significant increase in ejection fraction. CONCLUSIONS:
      Indices of left ventricular function were comparable between groups with no
      clinically significant change following atropine administration. The present
      study confirms the favorable hemodynamic profile of sevoflurane in infants
      breathing spontaneously at 1 MAC concentration.

PMID- 17498016
TI  - When to add supplemental rectal paracetamol for postoperative analgesia with
      caudal bupivacaine in children? A prospective, double-blind, randomized study.
AB  - BACKGROUND: The aim of this study was to investigate whether a supplemental dose
      of rectal paracetamol at the third or fourth hour would enhance the quality of
      analgesia provided by caudal epidural blockade in children. METHODS: Two hundred
      and two ASA I patients aged 1-12 years undergoing inguinal surgery were
      randomized into three groups in the postanesthesia care unit by drawing lots.
      Patients in the control group did not receive any analgesic until they had a pain
      score of 5 or higher, patients in the group P3 received rectal paracetamol (20-25
      mg x kg(-1)) at the third hour, and patients in the group P4 received the same
      dose of rectal paracetamol at the fourth hour after caudal epidural injection.
      Pain was assessed by VAS (Visual Analog Scale) and supplementary rescue analgesic
      need was recorded. RESULTS: There was no difference between the demographic data
      or the duration and variety of surgery among the groups. A significantly lower
      number of patients required rescue analgesia at the sixth postoperative hour in
      group P3 and also lower pain scores were again obtained in group P3 at the sixth
      and eighth postoperative hours. CONCLUSIONS: Supplemental rectal paracetamol at
      the third hour of caudal blockade enhances the quality of postoperative analgesia
      better than its addition at the fourth hour in children undergoing inguinal
      surgery.

PMID- 17498017
TI  - Is a fall in baseline heart rate a reliable predictor of a successful single shot
      caudal epidural in children?
AB  - BACKGROUND: This study was designed to investigate whether a fall in heart rate
      (HR) with injection of local anesthetic into the caudal space can be used as a
      predictor of correct needle placement. METHODS: Two hundred and twenty pediatric
      patients undergoing infraumbilical surgery were recruited to the study. After
      induction of general anesthesia, baseline HR was recorded and caudal block was
      performed using 0.75-1 ml x kg(-1) 0.25% bupivacaine, which was injected at a
      rate of 1 ml x 3 s(-1). The change in HR while injecting an initial 0.2 ml x kg(
      1) of drug and during total drug injection was recorded. HR reduction of > or = 3
      b x min(-1) was considered a positive test for correct needle placement. The
      success of block was judged by HR response to skin incision, endtidal halothane
      concentration required for maintenance of anesthesia and postoperative pain
      scores. RESULTS: Caudal block was successful in 209/220 (95%) patients. Mean HR
      following the initial drug injection (111 +/- 17.7, P < 0.01) and entire drug
      injection (108.8 +/- 17.2, P < 0.01) was significantly lower than baseline (116.2
      +/- 17.5). HR reduction of > or = 3 b x min(-1) was present in 190/209 and
      199/209 successful block following initial drug injection and total drug
      injection respectively. The analysis of study data showed that a fall in HR is a
      predictor of successful caudal block, with a sensitivity of 90.9%, specificity of
      100% and a positive predictive value of 100% after initial injection of local
      anesthetic. CONCLUSIONS: We conclude that decrease in HR with drug injection is a
      simple, objective and reliable test to predict success of caudal block.

PMID- 17498018
TI  - Tracheoscopy assisted repair of tracheo-esophageal fistula (TARTEF): a 10-year
      experience.
AB  - BACKGROUND: Fiberoptic tracheoscopy assisted repair of tracheoesophageal fistula
      (TARTEF) has been reported to be useful for the surgeon with regards to
      identification of the fistula and proper fistula ligation. The aim of this
      article is to report our 10-year experience using TARTEF with intermittent
      positive pressure ventilation (IPPV) during tracheoesophageal fistula (TEF)
      repair in newborns. METHODS: With ethical committee approval, we included all
      patients undergoing TARTEF from 1995-2005. Variables of interest were (1)
      respiratory deterioration caused by gastric inflation because of IPPV during
      surgery and endoscopy; (2) detection of additional airway anomalies; (3) success
      of intubation of the fistula; (4) other side effects or adverse events. Data are
      given in median and range. RESULTS: Forty-seven neonates with TARTEF were
      included. Mean gestational age was 37 weeks (31-42) and mean weight was 2.5 kg
      (1.1-3.8). The patients were intubated with tracheal tubes size 2.5-3.5 mm ID.
      Appropriately sized fiberoptic bronchoscopes with an outer diameter of 2.0, 2.4
      and 2.8 mm were used; passed through the lumen of the tracheal tube (TT) thereby
      requiring the use of IPPV to ensure adequate ventilation. No respiratory
      deterioration was noted as a consequence of intraoperative fiberoptic
      manipulation within the trachea or because of gastric hyperinflation with IPPV.
      In all patients, the TEF was successfully penetrated with the fiberscope and this
      clearly helped the surgeon to rapidly identify and dissect the fistula. In two
      patients a tracheal bronchus was identified. In two patients accidental
      extubation occurred during endoscopic confirmation of successful fistula repair.
      CONCLUSIONS: While fiberoptic TARTEF through the tracheal tube with IPPV did
      expedite and facilitate surgery, it did not cause clinically relevant impairment
      of ventilation. Careful manipulation during fiberoptic assessment is required to
      avoid tube displacement.

PMID- 17498020
TI  - Assessment of small-dose fentanyl and sufentanil blunting the cardiovascular
      responses to laryngoscopy and intubation in children.
AB  - BACKGROUND: The authors found no study assessing the efficacy of small-dose
      narcotics on the cardiovascular response from intubation in children, so they
      observed the effects of fentanyl 2 microg x kg(-1) and sufentanil 0.2 microg x
      kg(-1) on the cardiovascular changes during laryngoscopy and intubation in
      children. METHODS: Ninety-three children aged 3-9 years were randomized to one of
      three groups to receive the following treatments in a double-blind manner: normal
      saline (group C), fentanyl 2 microg x kg(-1) (group F) and sufentanil 0.2 microg
      x kg(-1) (group S) 2 min before induction. Noninvasive blood pressure (BP) and
      heart rate (HR) were recorded before anesthesia induction (baseline value),
      immediately before intubation (postinduction values), at intubation and 5 min
      after intubation at 1-min interval. RESULTS: Tracheal intubation caused
      significant increases in BP and HR in the three groups compared with baseline
      values. BP and HR at intubation and after intubation and their maximum values
      during observation were significantly lower in groups F and S than in group C (P
      < 0.05). The mean percent increases of systolic blood pressure (SBP) and HR at
      intubation were significantly lower in group S, 7% and 10%, than in group F, 17%
      and 25% (P < 0.05). The increases in SBP and HR of more than 30% of baseline
      values during the observation period were significantly higher in group F, 27%
      and 43%, than in group S, 0% and 3% (P < 0.05). CONCLUSIONS: When used as part of
      anesthesia induction with propofol in children, sufentanil 0.2 microg x kg(-1) 2
      min before induction is more effective in attenuating the cardiovascular
      intubation response than fentanyl 2 microg x kg(-1).

PMID- 17498019
TI  - The effects of sevoflurane and desflurane anesthesia on QTc interval and cardiac
      rhythm in children.
AB  - BACKGROUND: Inhalational anesthetics may prolong QTc interval (QT interval
      corrected for heart rate) of the ECG and cause life-threatening arrythmias. The
      effects of desflurane on QTc interval and cardiac rhythm have not been reported
      previously in children. We assessed the effects of desflurane anesthesia on QTc
      interval and cardiac rhythm and compared them with sevoflurane anesthesia in
      children. METHODS: The study was performed on 20 children admitted for inguinal
      hernia repair, with normal QTc intervals. Anesthesia was induced with propofol
      and intubation was achieved with vecuronium. Anesthesia was maintained with 2%
      sevoflurane (group I, n = 11) or 6% desflurane (group II, n = 9) and 66% nitrous
      oxide in oxygen. Electrocardiogram recordings were obtained by Holter recorder.
      QTc intervals were measured at baseline, 5, 10, 15, and 30 min after inhalation.
      RESULTS: None of the patients had significant arrythmia with desflurane
      anesthesia. One patient in the sevoflurane group had single, bigemini and
      multiform ventricular extrasystoles. There was no statistically significant
      difference in the baseline QTc values of the groups. Desflurane significantly
      prolonged QTc interval 5 min after induction until 30 min of anesthesia compared
      with baseline values (P = 0.029), while no significant prolongation was observed
      with sevoflurane (P = 0.141). CONCLUSIONS: Use of 2% sevoflurane during
      maintenance of anesthesia does not significantly prolong QTc interval while 6%
      desflurane significantly prolonged QTc interval in children with normal QTc
      interval undergoing inguinal herniorrhaphy.

PMID- 17498021
TI  - Unplanned anesthesia-related admissions to pediatric intensive care - a 6-year
      audit.
AB  - BACKGROUND: Unplanned admissions to the intensive care unit may result from
      unexpected events related to anesthesia, and are recommended by some healthcare
      organizations as a clinical indicator. The rate of anesthesia-related unplanned
      admissions in adults ranges between 0.04% and 0.45% of procedures. However, there
      is a paucity of data relating to the rate in children. METHODS: Admissions to the
      pediatric intensive care unit (PICU) occurring within 24 h of anesthesia were
      identified through retrospective chart review. Only those admissions from a
      complication of anesthesia were included and not those from communication errors
      or surgical problems. The aim was to determine the rate of unplanned admissions,
      as well as the causes and management of this group of unplanned admissions.
      RESULTS: Seventy-six children requiring admission to the PICU were identified
      from 55196 procedures during the 6-year study period. The rate of unplanned
      admission was 0.14% of procedures. A total of 47% of these admissions were
      related to airway problems and 68% of children requiring admission were aged less
      than 5 years. Most children required only observation after their admission.
      CONCLUSIONS: We found the unplanned admission rate to the PICU in our hospital
      population to be similar to that reported for adults, and is a relatively rare
      event in pediatric anesthesia. Most admissions were for children aged less than 5
      years and were as a result of airway problems. Most cases were deemed potentially
      predictable.

PMID- 17498022
TI  - Dexmedetomidine as a total intravenous anesthetic in infants.
AB  - In this case report, we describe the use of dexmedetomidine as the sole
      anesthetic for four infants requiring general anesthesia for direct laryngoscopy
      and bronchoscopy with spontaneous ventilation. Surgical conditions were adequate
      and the hemodynamic and respiratory profiles of this technique are described.

PMID- 17498023
TI  - Hemolytic-uremic syndrome and myocardial dysfunction in a 9-month-old boy.
AB  - Cardiovascular dysfunction in patients with hemolytic-uremic syndrome (HUS) may
      be related to secondary issues such as volume overload, hypertension or
      electrolyte disturbances including hyperkalemia. Additionally, primary myocardial
      involvement has been increasingly recognized as a potential comorbid feature of
      HUS. We report a 9-month-old child with HUS who developed clinical signs of poor
      myocardial function with depressed myocardial function noted by echocardiography.
      Supportive care including mechanical ventilation and inotropic agents were
      necessary for approximately 10 days. Follow-up echocardiography revealed return
      of normal ventricular function. Previous reports of primary cardiac involvement
      with HUS have included thrombotic microangiopathy of the coronary vasculature
      resulting in myocardial ischemia, myocardial infarction or depressed myocardial
      function, myocarditis, congestive heart failure with dilated cardiomyopathy and
      pericardial effusion with tamponade. Given the potential for morbidity and
      mortality during the preoperative period in patients with HUS, anesthesiologists
      involved in the care of such patients should be aware of the potential for
      myocardial involvement in this disease process. Preoperatively, the routine
      evaluation of myocardial function may be indicated.

PMID- 17498024
TI  - Survival of a child without sequelae after tracheoarterial fistula.
AB  - Tracheoarterial fistula (TAF) involves erosion through the tracheal wall into the
      innominate artery resulting in bleeding. It is a rare but lethal complication of
      tracheostomy. Mortality is 100% without operative interference. Even with
      appropriate management, a survival rate of only 14.3% has been reported. We
      report a case of TAF in a child, where rapid institution of resuscitative and
      operative measures resulted in survival. Initial temporary control of bleeding
      was achieved by hyperinflation of cuff. Computed tomography (CT) angiography
      confirmed the diagnosis. The damaged segment of the eroded artery was resected
      and ligated. This case highlights the role of early diagnosis and prompt
      aggressive therapy for management of this potentially lethal complication.

PMID- 17498025
TI  - Deep sedation with intravenous infusion of combined propofol and ketamine during
      dressing changes and whirlpool bath in patients with severe epidermolysis
      bullosa.
AB  - Continuous i.v. infusion of propofol, or propofol plus ketamine for deep sedation
      and analgesia was carried out in two patients with severe epidermolysis bullosa
      (EB) during extensive dressing changes and deep whirlpool baths. Intermittent
      small doses of narcotics were given as supplement for pain relief as needed. Both
      patients had typical features of severe EB, including extremity contractures,
      severe digit deformity, difficult airways, extensive blisters and broken skin
      with denuded areas and severe wound infections. SpO(2) was roughly estimated by
      holding the probe around the earlobe periodically and no other monitors could be
      applied because of the skin conditions and the settings of the procedures.
      Retrospective anesthesia record review showed that the combined propofol and
      ketamine infusions provided satisfactory sedation with significantly reduced
      narcotic requirements compared with propofol alone. There were no noticeable side
      effects when ketamine was added. Ketamine appears to be a good addition to
      propofol and narcotics to provide sedation and analgesia when there are great
      concerns for respiration depression, apnea, difficult pain management and
      potential unstable hemodynamics during dressing changes and whirlpool baths in
      severe EB patients.

PMID- 17498026
TI  - Transient postoperative harlequin syndrome combined with Horner's syndrome in a
      pediatric patient after neck mass excision.

PMID- 17498027
TI  - Near infrared spectroscopy used to detect preoperative aortic obstruction.

PMID- 17498028
TI  - Preventing kinking of suction tubing of transposable electrical suction device
      and wall mounted vacuum units.

PMID- 17498029
TI  - The 'Doppler-swoosh' test: a further modification to the 'swoosh' test.

PMID- 17498031
TI  - Pressure on the neck during laryngoscopy.

PMID- 17498034
TI  - Cuffed tracheal tubes in children - things have changed.

PMID- 17498035
TI  - Anesthetic management of a newborn with Mohr (oro-facial-digital type II)
      syndrome.

PMID- 17498036
TI  - Drug delivery via the tracheal tube using an airway device. A warning.

PMID- 17498047
TI  - The essential role of mast cells in orchestrating inflammation.

PMID- 17498048
TI  - Pathways of murine mast cell development and trafficking: tracking the roots and
      routes of the mast cell.
AB  - The appreciation of the role of the mast cell (MC) in inflammatory processes has
      expanded dramatically during the last decade. Many of these processes, especially
      more prolonged responses, are accompanied by an increase in the number of MCs,
      and much of this increase is likely because of recruitment of immature
      progenitors with subsequent maturation under the control of the tissue
      microenvironment. We have begun to identify many of the cell-surface molecules
      that control this influx and have traced the development of these cells back to
      their hematopoietic roots. This development proceeds along the myelomonocytic
      pathway with distinct intermediates having been identified in both bone marrow
      and spleen. The expression of alpha4beta7 integrins has played a prominent role
      in this process, as it helped identify a bipotent basophil MC precursor in the
      spleens of C57BL/6 mice. This integrin also controls basal influx into the
      intestine and, along with alpha4beta1 integrins, plays a critical role in
      recruitment to inflamed lungs. Investigation of chemokines and chemokine
      receptors in these processes led to the identification of a dual role for the
      murine interleukin-8 receptor CXCR2. This alpha-chemokine receptor affects MC
      progenitor trafficking by its expression by MC progenitors and by its expression
      on stromal cells, likely endothelium, affecting trafficking to both intestine
      under basal conditions and lung during inflammatory recruitment.

PMID- 17498049
TI  - Synovial mast cells: role in acute and chronic arthritis.
AB  - Mast cells reside in the normal synovium and increase strikingly in number in
      rheumatoid arthritis and other joint diseases. Given the broad spectrum of
      activity of this lineage, it has for decades been considered probable that mast
      cells are involved in the pathophysiology of synovitis. Recent work in murine
      arthritis has substantiated this suspicion, showing that mast cells can
      contribute importantly to the initiation of inflammatory arthritis. However, the
      role of the greatly expanded population of synovial mast cells in established
      arthritis remains unknown. Here we review the current understanding of mast cell
      function in acute arthritis and consider the potentially important influence of
      this cell on key processes within the chronically inflamed synovium, including
      leukocyte recruitment and activation, fibroblast proliferation, angiogenesis,
      matrix remodeling, and injury to collagen and bone. We also consider recent
      evidence supporting an immunomodulatory or anti-inflammatory role for mast cells
      as well as pharmacologic approaches to the mast cell as a therapeutic target in
      inflammatory arthritis.

PMID- 17498050
TI  - Mast cells in the pathogenesis of rheumatic diseases and as potential targets for
      anti-rheumatic therapy.
AB  - Increasing evidence suggests that mast cells (MCs), in addition to acute allergic
      reactions, are involved in the pathogenesis of chronic inflammatory diseases and
      in particular in rheumatoid arthritis (RA). MCs reside in connective tissues and
      in synovial tissue of joints. They produce an array of proinflammatory mediators,
      tissue destructive proteases, and cytokines, most prominently tumor necrosis
      factor-alpha, which is one of the key cytokines in the pathogenesis of RA. MCs
      may also participate in the development of secondary or amyloid A amyloidosis, as
      the partial degradation of the serum amyloid A (SAA) protein by MCs leads to the
      generation of a highly amyloidogenic N-terminal fragment of SAA. MCs may
      contribute to the pathogenesis of connective tissue diseases, scleroderma,
      vasculitic syndromes, and systemic lupus erythematosus, although the data
      available are limited. Inhibition of the most important growth factor receptor of
      human MCs, c-Kit, by the selective tyrosine kinase inhibitor imatinib mesylate,
      induces apoptosis of synovial tissue MCs. As MCs are long-lived cells, induction
      of their apoptosis could be a feasible approach to inhibit their functions.
      Preliminary findings suggest that a drug that inhibits c-Kit could have anti
      rheumatic activity in the treatment of patients with RA and
      spondyloarthropathies.

PMID- 17498051
TI  - Mast cells as modulators of T-cell responses.
AB  - Although mast cells have long been considered the integral effector cell in
      allergy and atopic disease, the paradigm of mast cell function is now evolving to
      incorporate data showing that mast cells make innumerable contributions to both
      protective and pathologic immune responses. Mast cells express cell surface
      molecules with costimulatory or co-inhibitory activity and produce a multitude of
      mediators that can direct dendritic cell (DC) or T-cell differentiation and
      function. In addition, mast cells exhibit a widespread distribution and are in
      close proximity to DCs and T cells at several critical sites. While there has
      been amazing progress in characterizing mast cell populations in vitro, only
      recently has the ability to monitor their in vivo effects become a reality. In
      this review, we discuss the evolution of our understanding of mast cell biology
      with an emphasis on their established and hypothesized roles in influencing T
      cell differentiation and function. The fact that T-cell and mast cell
      interactions exist and are a normal component of most adaptive immune responses
      is one of the best illustrations of the now established concept that innate and
      adaptive immunity are not completely independent entities.

PMID- 17498052
TI  - Differential release of mast cell mediators and the pathogenesis of inflammation.
AB  - Mast cells are well known for their involvement in allergic and anaphylactic
      reactions, during which immunoglobulin E (IgE) receptor (Fc epsilon RI)
      aggregation leads to exocytosis of the content of secretory granules (1000 nm),
      commonly known as degranulation, and secretion of multiple mediators. Recent
      findings implicate mast cells also in inflammatory diseases, such as multiple
      sclerosis, where mast cells appear to be intact by light microscopy. Mast cells
      can be activated by bacterial or viral antigens, cytokines, growth factors, and
      hormones, leading to differential release of distinct mediators without
      degranulation. This process appears to involve de novo synthesis of mediators,
      such as interleukin-6 and vascular endothelial growth factor, with release
      through secretory vesicles (50 nm), similar to those in synaptic transmission.
      Moreover, the signal transduction steps necessary for this process appear to be
      largely distinct from those known in Fc epsilon RI-dependent degranulation. How
      these differential mast cell responses are controlled is still unresolved. No
      clinically available pharmacological agents can inhibit either degranulation or
      mast cell mediator release. Understanding this process could help develop mast
      cell inhibitors of selective mediator release with novel therapeutic
      applications.

PMID- 17498053
TI  - Mast cells and inflammatory kidney disease.
AB  - Inflammatory kidney disease involves a complex network of interactions between
      resident kidney and infiltrating hematopoietic cells. Mast cells (MCs) are
      constitutively found in kidneys in small numbers but increase considerably in
      various renal diseases. While this increase is usually interpreted as a sign of
      pathological involvement, recent data using MC-deficient animals show their
      ability to restore kidney homeostasis. In anti-glomerular basement membrane
      antibody-induced glomerulonephritis, MCs are protective by initiating repair and
      remodeling functions counteracting the devastating effects of glomerular injury.
      Protection may also include immunoregulatory capacities to limit autoreactive T
      cell responses. MCs also control tubulointerstitial fibrosis by activating tissue
      remodeling and neutralizing fibrotic factors. Release of mediators by MCs during
      inflammation, however, could also promote unwanted responses that ultimately lead
      to destruction of kidney structure, as exemplified by data showing either
      protection or aggravation in related renal disease models. Similarly, while the
      action of proteases may initially be beneficial, the generation of fibrosis
      promoting angiotensin II by chymase also shows the limits of adaptive responses
      to achieve homeostasis. Thus, it is likely the physiological context involving
      the interaction with other cells and inflammatory mediators that determines the
      final action of MCs in the development of kidney disease.

PMID- 17498054
TI  - Role of beta-chemokines in mast cell activation and type I hypersensitivity
      reactions in the conjunctiva: in vivo and in vitro studies.
AB  - Chemokines have a clearly defined role in mobilizing the recruitment of
      leukocytes to both healthy and inflamed tissues. This review details work from
      our and other laboratories, indicating that beta-chemokines may play important
      roles (i) in driving the terminal differentiation of mast cell precursors in
      mucosal tissues and (ii) in providing priming or costimulatory signals required
      for mast cell activation, leading to an antigen-driven inflammatory response.
      These data stem from in vivo, ex vivo, and in vitro studies. Data are also
      presented that suggest that Fc epsilon RI:chemokine receptor cross talk may
      involve spatiotemporal dynamics that may control the strength and nature of the
      complex activating signals controlling mast cell effector function.

PMID- 17498055
TI  - Mast cells: multipotent local effector cells in atherothrombosis.
AB  - Our understanding of the relationship between the proatherogenic activities of
      arterial mast cells (MCs) and the development of atherosclerotic lesions is
      advancing. Atherosclerosis is a chronic inflammatory disease in which cholesterol
      and other lipids of circulating low-density lipoprotein (LDL) particles
      accumulate both extracellularly and intracellularly in the innermost layer of the
      arterial wall, the intima. One prerequisite for the proatherogenic activity of
      the LDL particles is their retention and proteolytic modification within the
      extracellular matrix of the intima. Experimental studies with activated chymase
      secreting MCs have provided us fundamental insights into the molecular mechanisms
      of these processes. High-density lipoprotein (HDL) particles, again, remove
      cholesterol from the intracellular stores and carry it back to the circulation.
      MC chymase and tryptase actively degrade HDL and thus generate functionally
      defective particles that are unable to initiate cholesterol efflux from the
      arterial wall. In advanced atherosclerotic plaques, the accumulated lipids are
      separated from the circulation by a collagenous cap. By inducing apoptosis of
      endothelial cells (ECs), subendothelial MCs may induce detachment of ECs from the
      cap (plaque erosion). Moreover, MCs may weaken the cap if they disturb local
      collagen turnover by inducing apoptosis of the collagen-secreting smooth muscle
      cells or when they promote collagen degradation by activating matrix
      metalloproteinases. Plaques with a weak cap are vulnerable to rupture. The
      exposed subendothelial tissue at eroded and ruptured sites of plaques triggers
      local development of a platelet-rich thrombus. As regulators of the collagen
      induced platelet activation and fibrin formation/fibrinolysis, the MCs may retard
      or accelerate the growth of the plaque-associated thrombus and ultimately
      participate in the wound-healing response of the injured plaque. We propose that
      by promoting cholesterol accumulation and plaque vulnerability and by locally
      regulating hemostasis, MCs in atherosclerotic lesions have the potential to
      contribute to the clinical outcomes of atherosclerosis, such as myocardial
      infarction and stroke.

PMID- 17498056
TI  - Renin: at the heart of the mast cell.
AB  - Cardiac mast cells proliferate in cardiovascular diseases. In myocardial
      ischemia, mast cell mediators contribute to coronary vasoconstriction,
      arrhythmias, leukocyte recruitment, and tissue injury and repair. Arrhythmic
      dysfunction, coronary vasoconstriction, and contractile failure are also
      characteristic of cardiac anaphylaxis. In coronary atherosclerosis, mast cell
      mediators facilitate cholesterol accumulation and plaque destabilization. In
      cardiac failure, mast cell chymase causes myocyte apoptosis and fibroblast
      proliferation, leading to ventricular dysfunction. Chymase and tryptase also
      contribute to fibrosis in cardiomyopathies and myocarditis. In addition, mast
      cell tumor necrosis factor-alpha promotes myocardial remodeling. Cardiac
      remodeling and hypertrophy in end-stage hypertension are also induced by mast
      cell mediators and proteases. We recently discovered that cardiac mast cells
      contain and release renin, which initiates local angiotensin formation.
      Angiotensin causes coronary vasoconstriction, arrhythmias, fibrosis, apoptosis,
      and endothelin release, all demonstrated mechanisms of mast-cell-associated
      cardiac disease. The effects of angiotensin are further amplified by the release
      of norepinephrine from cardiac sympathetic nerves. Our discovery of renin in
      cardiac mast cells and its release in pathophysiological conditions uncovers an
      important new pathway in the development of mast-cell-associated heart diseases.
      Several steps in this novel pathway may constitute future therapeutic targets.

PMID- 17498058
TI  - Protease-proteoglycan complexes of mouse and human mast cells and importance of
      their beta-tryptase-heparin complexes in inflammation and innate immunity.
AB  - Approximately 50% of the weight of a mature mast cell (MC) consists of varied
      neutral proteases stored in the cell's secretory granules ionically bound to
      serglycin proteoglycans that contain heparin and/or chondroitin sulfate E/diB
      chains. Mouse MCs express the exopeptidase carboxypeptidase A3 and at least 15
      serine proteases [designated as mouse MC protease (mMCP) 1-11, transmembrane
      tryptase/tryptase gamma/protease serine member S (Prss) 31, cathepsin G, granzyme
      B, and neuropsin/Prss19]. mMCP-6, mMCP-7, mMCP-11/Prss34, and Prss31 are the four
      members of the chromosome 17A3.3 family of tryptases that are preferentially
      expressed in MCs. One of the challenges ahead is to understand why MCs express so
      many different protease-proteoglycan macromolecular complexes. MC-like cells that
      contain tryptase-heparin complexes in their secretory granules have been
      identified in the Ciona intestinalis and Styela plicata urochordates that
      appeared approximately 500 million years ago. Because sea squirts lack B cells
      and T cells, it is likely that MCs and their tryptase-proteoglycan granule
      mediators initially appeared in lower organisms as part of their innate immune
      system. The conservation of MCs throughout evolution suggests that some of these
      protease-proteoglycan complexes are essential to our survival. In support of this
      conclusion, no human has been identified that lacks MCs. Moreover, transgenic
      mice lacking the beta-tryptase mMCP-6 are unable to combat a Klebsiella
      pneumoniae infection effectively. Here we summarize the nature and function of
      some of the tryptase-serglycin proteoglycan complexes found in mouse and human
      MCs.

PMID- 17498057
TI  - Mast cell tryptases and chymases in inflammation and host defense.
AB  - Tryptases and chymases are the major proteins stored and secreted by mast cells.
      The types, amounts, and properties of these serine peptidases vary by mast cell
      subtype, tissue, and mammal of origin. Membrane-anchored gamma-tryptases are
      tryptic, prostasin-like, type I peptidases that remain membrane attached on
      release and act locally. Soluble tryptases, including their close relatives,
      mastins, form inhibitor-resistant oligomers that act more remotely. Befitting
      their greater destructive potential, chymases are quickly inhibited after
      release, although some gain protection by associating with proteoglycans. Most
      chymase-like enzymes, including mast cell cathepsin G, hydrolyze chymotryptic
      substrates, an uncommon capability in the proteome. Some rodent chymases,
      however, have mutations resulting in elastolytic activity. Secreted tryptases and
      chymases promote inflammation, matrix destruction, and tissue remodeling by
      several mechanisms, including destroying procoagulant, matrix, growth, and
      differentiation factors and activating proteinase-activated receptors, urokinase,
      metalloproteinases, and angiotensin. They also modulate immune responses by
      hydrolyzing chemokines and cytokines. At least one chymase protects mice from
      intestinal worms. Tryptases and chymases can also oppose inflammation by
      inactivating allergens and neuropeptides causing inflammation and
      bronchoconstriction. Thus, like mast cells themselves, mast cell serine
      peptidases play multiple roles in host defense, and any accounting of benefit
      versus harm is necessarily context specific.

PMID- 17498059
TI  - Mast cells and eicosanoid mediators: a system of reciprocal paracrine and
      autocrine regulation.
AB  - When activated by specific antigen, complement, or other transmembrane stimuli,
      mast cells (MCs) generate three eicosanoids: prostaglandin (PG)D(2), leukotriene
      (LT)B(4), and LTC(4), the parent molecule of the cysteinyl leukotrienes (cysLTs).
      These diverse lipid mediators, which are generated from a single cell membrane
      associated precursor, arachidonic acid, can initiate, amplify, or dampen
      inflammatory responses and influence the magnitude, duration, and nature of
      subsequent immune responses. PGD(2) and cysLTs, which were originally recognized
      for their bronchoconstricting and vasoactive properties, also serve diverse and
      pivotal functions in effector cell trafficking, antigen presentation, leukocyte
      activation, matrix deposition, and fibrosis. LTB(4) is a powerful chemoattractant
      for neutrophils and certain lymphocyte subsets. Thus, MCs can contribute to each
      of these processes through eicosanoid generation. Additionally, MCs express G
      protein-coupled receptors specific for cysLTs, LTB(4), and another eicosanoid,
      PGE(2). Each of these receptors can regulate MC functions in vivo by autocrine
      and paracrine mechanisms. This review focuses on the biologic functions for MC
      associated eicosanoids, the regulation of their production, and the mechanisms by
      which eicosanoids may regulate MC function in host defense and disease.

PMID- 17498060
TI  - The role of reactive oxygen species and nitric oxide in mast cell-dependent
      inflammatory processes.
AB  - Reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS),
      including nitric oxide, are produced in cells by a variety of enzymatic and non
      enzymatic mechanisms. At high levels, both types of oxidants are used to kill
      ingested organisms within phagocytes. At low levels, RNOS may diffuse outside
      cells where they impact the vasculature and nervous system. Recent evidence
      suggests that low levels of ROS produced within cells are involved in cell
      signaling. Along with these physiological roles, many pathological conditions
      exist where detrimental high-level ROS and RNOS are produced. Many situations in
      which ROS/RNOS are associated also involve mast cell activation. In innate
      immunity, such mast cells are involved in the immune response toward pathogens.
      In acquired immunity, activation of mast cells by cross-linking of receptor-bound
      immunoglobulin E causes the release of mediators involved in the allergic
      inflammatory response. In this review, we describe the principle pathways for ROS
      and RNOS generation by cells and discuss the existence of such pathways in mast
      cells. In addition, we examine the evidence for a functional role for ROS and
      RNOS in mast cell secretory responses and discuss evidence for a direct
      relationship between ROS, RNOS, and mast cells in mast cell-dependent
      inflammatory conditions.

PMID- 17498061
TI  - The mast cell IgG receptors and their roles in tissue inflammation.
AB  - Mast cells are effector cells of the innate immune system, but because they
      express Fc receptors (FcRs), they can be engaged in adaptive immunity by
      antibodies. Mast cell FcRs include immunoglobulin E (IgE) and IgG receptors and,
      among these, activating and inhibitory receptors. The engagement of mast cell IgG
      receptors by immune complexes may or may not trigger cell activation, depending
      on the type of mast cell. The coengagement of IgG and IgE receptors results in
      inhibition of mast cell activation. The Src homology-2 domain-containing inositol
      5-phosphatase-1 is a major effector of negative regulation. Biological responses
      of mast cells depend on the balance between positive and negative signals that
      are generated in FcR complexes. The contribution of human mast cell IgG receptors
      in allergies remains to be clarified. Increasing evidence indicates that mast
      cells play critical roles in IgG-dependent tissue-specific autoimmune diseases.
      Convincing evidence was obtained in murine models of multiple sclerosis,
      rheumatoid arthritis, bullous pemphigoid, and glomerulonephritis. In these
      models, the intensity of lesions depended on the relative engagement of
      activating and inhibitory IgG receptors. In vitro models of mature tissue
      specific murine mast cells are needed to investigate the roles of mast cells in
      these diseases. One such model unraveled unique differentiation/maturation
      dependent biological responses of serosal-type mast cells.

PMID- 17498062
TI  - Inhibition of pathologic inflammation by leukocyte Ig-like receptor B4 and
      related inhibitory receptors.
AB  - Leukocyte immunoglobulin (Ig)-like receptor B4 (LILRB4)(previously termed gp49B1)
      is a member of the Ig superfamily expressed constitutively on the surface of mast
      cells, neutrophils, and macrophages. LILRB4 inhibits IgE-dependent activation of
      mast cells in vitro through its two immunoreceptor tyrosine-based inhibitory
      motifs (ITIMs) that recruit the src homology domain type-2-containing tyrosine
      phosphatase 1 into the cell membrane. Accordingly, Lilrb4(-/-) mice exhibit
      greater incidence and severity of IgE- and mast cell-dependent anaphylactic
      inflammation compared with mice that express LILRB4. In addition, mast cell
      dependent inflammation induced by the interaction of stem cell factor (SCF) with
      its receptor Kit is also more severe in Lilrb4(-/-) mice, indicating that the
      counterregulatory function of LILRB4 extends beyond inflammation induced by Fc
      receptors, which signal through ITIMs, to responses initiated through a receptor
      tyrosine kinase. Indeed, pathologic inflammatory responses induced by activation
      of neutrophils with lipopolysaccharide (LPS) alone or with tissue-specific
      autoantibodies are greatly exacerbated in Lilrb4(-/-) mice. The rapid
      upregulation of LILRB4 expression on neutrophils in Lilrb4(+/+) mice in response
      to LPS suggests it is an innate counterregulatory response designed to reduce
      pathologic inflammation. Nevertheless, LILRB4 also serves a similar purpose for
      inflammation induced by the humoral adaptive immune response that is manifested
      through effector cells bearing Fc receptors.

PMID- 17498063
TI  - Regulation of the mast cell response to the type 1 Fc epsilon receptor.
AB  - The type I Fc epsilon receptor (Fc epsilon RI) is one of the better understood
      members of its class and is central to the immunological activation of mast cells
      and basophils, the key players in immunoglobulin E (IgE)-dependent immediate
      hypersensitivity. This review provides background information on several distinct
      regulatory mechanisms controlling this receptor's stimulus-response coupling
      network. First, we review the current understanding of this network's operation,
      and then we focus on the inhibitory regulatory mechanisms. In particular, we
      discuss the different known cytosolic molecules (e.g. kinases, phosphatases, and
      adapters) as well as cell membrane proteins involved in negatively regulating the
      Fc epsilon RI-induced secretory responses. Knowledge of this field is developing
      at a fast rate, as new proteins endowed with regulatory functions are still being
      discovered. Our understanding of the complex networks by which these proteins
      exert regulation is limited. Although the scope of this review does not include
      addressing several important biochemical and biophysical aspects of the
      regulatory mechanisms, it does provide general insights into a central field in
      immunology.

PMID- 17498064
TI  - Src family kinases and lipid mediators in control of allergic inflammation.
AB  - The Src family kinases Fyn and Lyn are important modulators of the molecular
      events initiated by engagement of the high-affinity IgE receptor (Fc epsilon RI).
      These kinases control many of the early signaling events and initiate the
      production of several lipid metabolites that have an important role in regulating
      mast cell responses. The intracellular level of phosphatidylinositol (3,4,5)
      trisphosphate (PIP(3)), which is produced by phosphatidylinositol 3-OH kinase,
      plays an important role in determining the extent of a mast cells response to a
      stimulus. Enhanced levels lead to a hyperdegranulating phenotype (as seen in SHIP
      1(-/-) and Lyn(-/-) mast cells), whereas decreased levels cause hypodegranulation
      (as seen in Fyn(-/-) mast cells). Downregulation of mast cell phosphatase and
      tensin homologue deleted on chromosone 10 expression, a phosphatase that reduces
      cellular levels of PIP(3), caused constitutive cytokine production, demonstrating
      that this response is particularly sensitive to PIP(3) levels. Lyn and Fyn are
      also intimately linked to other lipid kinases, like sphingosine kinases (SphK).
      By producing sphingosine-1-phosphate (S1P), SphKs contribute to mast cell
      chemotaxis and degranulation. In vivo studies now reveal that circulating S1P as
      well as that found within the mast cell is important in determining mast cell
      responsiveness. These studies demonstrate the connection between Src protein
      tyrosine kinases and lipid second messengers that control mast cell function and
      allergic responses.

PMID- 17498065
TI  - Insights into immunoglobulin E receptor signaling from structurally defined
      ligands.
AB  - The asymmetrical structure of bent immunoglobulin E (IgE) bound to its high
      affinity receptor, Fc epsilon RI, suggests a possible role for this configuration
      in the regulation of signaling mediated by cross-linking of Fc epsilon RI on the
      surface of mast cells and basophils. Indeed, the presence of bound IgE strongly
      influences the capacity of cross-linked Fc epsilon RI dimers to trigger mast cell
      degranulation, implicating orientational constraints by bound IgE. Bivalent
      ligands that cross-link by binding to bivalent IgE can form linear and cyclic
      chains of IgE/Fc epsilon RI complexes, and these exhibit only limited capacity to
      stimulate downstream signaling and degranulation, whereas structurally analogous
      trivalent ligands, which can form branched networks of cross-linked IgE/Fc
      epsilon RI complexes, are more effective at cell activation. Long bivalent
      ligands with flexible spacers can form intramolecular cross-links with IgE, and
      these stable 1:1 complexes are very potent inhibitors of mast cell degranulation
      stimulated by multivalent antigen. In contrast, trivalent ligands with rigid
      double-stranded DNA spacers effectively stimulate degranulation responses in a
      length-dependent manner, providing direct evidence for receptor
      transphosphorylation as a key step in the mechanism of signaling by Fc epsilon
      RI. Thus, studies with chemically defined oligovalent ligands show important
      features of IgE receptor cross-linking that regulate signaling, leading to mast
      cell activation.

PMID- 17498066
TI  - The role played by key transcription factors in activated mast cells.
AB  - The network of transcription factors in mast cells has not been investigated as
      widely as it has been in other differentiated hematopoietic cells. There are
      still many mechanisms of transcriptional regulation that need to be fully
      elucidated to understand how mast cell external stimuli lead to the appropriate
      physiological responses. Such information could be used to determine potential
      therapeutic targets for the control of mast cell activation in inflammatory
      diseases, allergy, and asthma. The aim of this article is to review hallmark
      studies in the field of transcription factor regulation in mast cells. We
      elaborate especially on several transcription factors studied in our laboratory
      in the past decade, including activator protein-1, microphthalmia-associated
      transcription factor, upstream stimulating factor-2, and signal transducer and
      activator of transcription 3.

PMID- 17498067
TI  - The mast cell: where endocytosis and regulated exocytosis meet.
AB  - We have investigated whether Ca(2+)-binding proteins, which have been implicated
      in the control of neurons and neuroendocrine secretion, play a role in
      controlling mast cell function. These studies have identified synaptotagmins
      (Syts) II, III, and IX as well as neuronal Ca(2+) sensor 1 (NCS-1) as important
      regulators of mast cell function. Strikingly, we find that these Ca(2+)-binding
      proteins contribute to mast cell function by regulating specific endocytic
      pathways. Syt II, the most abundant Syt homologue in mast cells, resides in an
      amine-free lysosomal compartment. Studying the function of Syt II-knocked down
      rat basophilic leukemia cells has shown a dual function of this homologue. Syt II
      is required for the downregulation of protein kinase Calpha, but it negatively
      regulates lysosomal exocytosis. Syt III, the next most abundant homologue,
      localizes to early endosomes and is required for the formation of the endocytic
      recycling compartment (ERC). Syt IX and NCS-1 localize to the ERC and regulate
      ERC export, NCS-1 by activating phosphatidylinositol 4-kinase beta. Finally, we
      show that recycling through the ERC is needed for secretory granule protein
      sorting as well as for the activation of the mitogen-activated protein kinases,
      extracellular signal-regulated kinase 1 and 2. Accordingly, NCS-1 stimulates Fc
      epsilon RI-triggered exocytosis and release of arachidonic acid metabolites.

PMID- 17498068
TI  - Mast cells in the promotion and limitation of chronic inflammation.
AB  - Observations of increased numbers of mast cells at sites of chronic inflammation
      have been reported for over a hundred years. Light and electron microscopic
      evidence of mast cell activation at such sites, taken together with the known
      functions of the diverse mediators, cytokines, and growth factors that can be
      secreted by appropriately activated mast cells, have suggested a wide range of
      possible functions for mast cells in promoting (or suppressing) many features of
      chronic inflammation. Similarly, these and other lines of evidence have
      implicated mast cells in a variety of adaptive or pathological responses that are
      associated with persistent inflammation at the affected sites. Definitively
      characterizing the importance of mast cells in chronic inflammation in humans is
      difficult. However, mice that genetically lack mast cells, especially those which
      can undergo engraftment with wildtype or genetically altered mast cells, provide
      a means to investigate the importance of mast cells and specific mast cell
      functions or products in diverse models of chronic inflammation. Such work has
      confirmed that mast cells can significantly influence multiple features of
      chronic inflammatory responses, through diverse effects that can either promote
      or, perhaps more surprisingly, suppress aspects of these responses.

PMID- 17498069
TI  - Human mast cells, bacteria, and intestinal immunity.
AB  - Mast cells are versatile tissue regulator cells controlling major intestinal
      functions such as epithelial secretion, epithelial permeability, blood flow,
      neuroimmune interactions, and peristalsis. Most importantly, mast cells are key
      regulators of the integrity and function of the gastrointestinal barrier. At the
      same time, they can act as immunomodulatory cells by reacting to various
      exogenous signals from bacteria, viruses, and parasites through innate
      recognition receptors, such as Toll-like receptors (TLRs) or through receptors of
      the specific immune system, such as immunoglobulins (Igs) bound to their cell
      surface. This mast cell function is enhanced by an intensive cross talk of mast
      cells with other cells of the innate or adaptive immune systems. Finally, mast
      cells act as inflammatory cells mediating diseases such as allergy, once they
      become dysregulated because of excess of allergen, allergen-specific IgE and
      cytokines, or invading microbes. The present article focuses on the human mast
      cell functions in the intestine and compares the data with those derived from
      animal experiments. In particular, the role of bacteria and TLRs expression by
      mast cells for allergic reactions are discussed.

PMID- 17498070
TI  - Prophylaxis in the haemophilia population-optimizing therapy.

PMID- 17498071
TI  - Reformulated BeneFix: efficacy and safety in previously treated patients with
      moderately severe to severe haemophilia B.
AB  - BeneFix, the only recombinant factor IX (FIX), has been reformulated. The
      reformulation involves a change in diluent and allows for more concentrated
      infusions of recombinant FIX. A double-blind, randomized, pharmacokinetic (PK)
      crossover study demonstrated that reformulated BeneFix was bioequivalent to
      original BeneFix and follow-up PK evaluation after 6 months of treatment
      demonstrated the PK stability of reformulated BeneFix after multiple exposures.
      Favourable efficacy and safety profiles, consistent with those already well
      established for original BeneFix, were observed: 81.1% of haemorrhages resolved
      with only a single infusion; 85.3% of initial treatment response ratings were
      Excellent or Good; more than half of the subjects using reformulated BeneFix for
      routine prophylaxis (11 of 17, 64.7%) had no spontaneous haemorrhages during
      their 6-12 month course of prophylactic treatment, with an overall spontaneous
      bleeding rate of 0.72 year(-1); and for the single surgical procedure (knee
      washing), treatment was rated Useful. In addition, there was no FIX inhibitor
      development, allergic-type manifestations, or thrombogenic complications with
      more than 1100 infusions (nearly 5.2 million IUs) administered in this trial. All
      efficacy and safety outcomes from this study were achieved with more concentrated
      recombinant protein infusions than that possible with original BeneFix, and
      utilization of the 2000 IU per vial dosage strength, newly introduced with the
      reformulated product, was high (>62%). The reformulation of BeneFix allows
      smaller delivery volumes and an increased choice of dosage strengths without
      altering the PK properties (including incremental recovery and half-life) or the
      established efficacy and safety profile of recombinant FIX.

PMID- 17498072
TI  - Sequential therapy with activated prothrombin complex concentrates and
      recombinant FVIIa in patients with severe haemophilia and inhibitors: update of
      our previous experience.
AB  - Haemophilia patients with inhibitors can develop bleeding episodes, which are
      refractory to monotherapy with either recombinant factor VIIa (rFVIIa) or
      activated prothrombin complex concentrates (APCC). Management of such bleeds is
      often difficult. We previously reported the safety of using a combination of
      rFVIIa and APCC given in sequential fashion. In this report, we update our
      experience with sequential therapy. A retrospective review of medical records was
      conducted including all reports of sequential therapy defined as receiving both
      rFVIIa and APCC within 6 h. Data extracted included demographic data, treatment
      prior to and following hospital admission, clinical data including type and
      location of bleed, response to therapy, physical examination and laboratory data.
      In addition, for some patients, thromboelastography was performed to document the
      effect of sequential therapy on clot formation characteristics. Four patients
      comprising 35 admissions, 209 hospital days and 115 days of sequential therapy
      were included in the updated dataset. No patient developed thrombosis or overt
      disseminated intravascular coagulation (DIC) although elevations in the D-dimer
      above 5 microg mL(-1) were noted in 42% of the courses that lasted >3 days.
      Efficacy is suggested by the fact that patients had resolution of their bleeds
      after a median of 3 days of sequential therapy after failing to respond to a
      median of 3 days of monotherapy. Thromboelastography demonstrated an additive
      effect. Sequential therapy is a safe, potentially efficacious approach in the
      management of refractory bleeding episodes in patients with haemophilia and
      inhibitors.

PMID- 17498073
TI  - Prophylactic treatment with activated prothrombin complex concentrate (FEIBA)
      reduces the frequency of bleeding episodes in paediatric patients with
      haemophilia A and inhibitors.
AB  - Orthopaedic complications are among the most disabling sequelae occurring in
      patients with haemophilia and inhibitors. Recurrent or refractory joint bleeds
      can lead to joint damage, limiting mobility and causing permanent disability.
      Activated prothrombin complex concentrates (aPCCs) are effective in controlling
      acute, intraoperative and postoperative bleeding in patients with haemophilia and
      inhibitors. The relatively long, dosing interval and safety profile distinguish
      aPCCs as a well-suited option for prophylaxis. Therefore, it is postulated that
      long-term routine aPCC administration will decrease the frequency of recurrent
      bleeds, prevent damage to normal joints, and slow the progression of existing
      joint disease in patients with inhibitors. To test this hypothesis, a
      retrospective chart audit was performed. In four treatment centres, five patients
      were identified who received aPCC [Factor Eight Inhibitor Bypassing Activity,
      Anti-Inhibitor Coagulant Complex (FEIBA); Baxter AG, Vienna, Austria]
      prophylactically for > or = 6 months to prevent or reduce further joint
      deterioration, reduce bleeding and prevent postsurgical bleeding. Median
      treatment duration was 15 months and included administration of >1300 doses of
      aPCC. Dosages ranged from 50 to 75 U kg(-1) three times per week in four
      patients; one patient received 100 U kg(-1) daily. Orthopaedic status was
      maintained in four patients and improved in one; the frequency of bleeding
      episodes was reduced in all patients. No adverse events or thrombotic
      complications were reported. This case series demonstrates that routine aPCC
      administration may be used safely and effectively to reduce the occurrence of
      bleeding episodes and to maintain or improve clinical joint status in some
      patients.

PMID- 17498074
TI  - A systematic approach to controlling problem bleeds in patients with severe
      congenital haemophilia A and high-titre inhibitors.
AB  - The presence of inhibitory antibodies to clotting factors complicates the
      treatment of bleeding in haemophilia patients. For patients with high-titre
      inhibitors, bypassing agents are essential to haemostatic management. To
      determine optimal treatment practices, an international panel of physicians
      convened to develop a systematic treatment approach for problem bleeds (i.e.
      bleeds that are unresponsive to initial therapy with a single agent within a
      reasonable amount of time) in haemophilia patients with inhibitors. AIM: The goal
      of this panel was to develop a consensus algorithm that would aid physicians in
      considering a variety of treatment approaches to optimize patient care by
      preventing extensive therapy with inadequate treatments that may lead to
      suboptimal patient outcomes and unnecessary costs. METHODS: Consensus opinions
      were analyzed for clinical preferences at different time periods, depending on
      patient response to treatment. Decision-making points were defined based on the
      type of bleed: every 8-12 h for the first 24 h, then every 24 h thereafter for
      limb-threatening bleeds; every 2-4 h for 2-7 days for life-threatening bleeds.
      RESULTS: The resultant consensus guidelines provide a generalized methodology to
      guide the treatment of problem bleeds in patients with severe haemophilia A and
      inhibitors, and emphasize changing treatment at the first sign of an inadequate
      haemostatic response. The treatment algorithms apply to both paediatric and adult
      patients, although the differences between the two groups were reviewed.
      CONCLUSION: These guidelines are focused on optimising the timing of treatment
      decisions, which may lead to faster responses and improved outcomes.

PMID- 17498075
TI  - Information and self-management needs of people living with bleeding disorders: a
      survey.
AB  - The aim of the study was to conduct a survey of information and self-management
      needs among members of the UK Haemophilia Society (HS). Of 1082 members mailed,
      307 took part in the survey, the mean age was 52.4 years (SD 14.8), 85% were
      male, 96% white and 66% were living with haemophilia A. 90% felt that there is a
      lack of understanding amongst the public regarding bleeding disorders, 76% felt
      that health professionals understood their health and information needs and 32%
      had experienced problems managing anxiety and or depression. Results suggest that
      there was a 'stigma' attached to having a bleeding disorder and almost half are
      very careful about informing others that they have a bleeding disorder. Self
      efficacy was relatively high within the sample. Many respondents wanted to be
      kept informed about current research and the opportunity to participate in
      research. Women experienced a greater need for more information than men,
      particularly in the area of the 'medical management' and 'emotional' topics. Men
      appeared to need more information and or training on 'physical' aspects such as
      physiotherapy and joint replacement. The study provides an insight into the
      educational and self-management needs of those affected by bleeding disorders and
      highlights the importance of providing accessible information.

PMID- 17498076
TI  - Trends in the utilization and wastage of coagulation factor concentrates: the
      application of a regional tracking programme.
AB  - The Commission of Inquiry on the Blood System in Canada ('Krever Commission',
      1997) recommended an active programme of surveillance for all blood products. To
      describe trends in the utilization of coagulation factor concentrates using a
      comprehensive factor tracking programme. Between 2001 and 2004 in the region of
      Southern Ontario, we prospectively tracked all coagulation factor concentrates
      that were distributed from the national blood supplier, issued by hospitals for
      inpatient use or for home infusions, infused at hospital facilities or at home
      and wasted. Discrepancies were reconciled by independent audits. Trends in the
      utilization of FVIII, FIX and FVIIa concentrates are reported. A total of 466
      patients with inherited or acquired bleeding disorders were registered.
      Utilization of FVIII, FIX and FVIIa increased by an average of 13.7%, 33.2% and
      34.2% per year respectively. Most FVIII and FIX infusions were administered at
      home while most FVIIa infusions were in hospital. The increase in FVIII and FIX
      usage was attributable to an increase in per-patient use, predominantly for
      prophylaxis. In total, 1.7% of coagulation factor concentrates was wasted during
      the study period, at a cost of over 1 million Canadian dollars. Utilization of
      coagulation factor concentrates increased steadily during the study period. A
      regional programme to track utilization is feasible and may be used to describe
      trends, assist planning, and reduce costs by minimizing wastage.

PMID- 17498077
TI  - Upper gastrointestinal bleeding in haemophiliacs: incidence and relation to use
      of non-steroidal anti-inflammatory drugs.
AB  - This multicentre study sought to estimate the incidence of upper gastrointestinal
      (UGI) bleeding in haemophiliacs and its relationship to use of non-steroidal anti
      inflammatory drugs (NSAIDs). Cox models were used to estimate relative hazards
      (RH) with 95% confidence intervals (CI) for postulated risk factors. Conditional
      logistic regression and stored sera were used to assess UGI bleeding risk with
      Heliobacter pylori seropositivity in cases compared with closely matched
      controls. During a mean of 17.4 months (range 2-34), 2285 participants, ages 13
      89 (mean 36.5) were followed for 3309 person-years (py). Forty-two experienced a
      UGI bleeding event (incidence 1.3 per 100 py), most from ulcer (11), gastritis
      (four), varices (five) and Mallory Weiss tears (eight). RH was significantly
      increased with traditional NSAID use for <1 month (OR: 3.66; 95% CI: 1.1-11.9),
      but not with coxibs use. RH was significantly and independently increased with
      age >46 years (3.5; 95% CI: 1.1-10.6) and hepatic decompensation (4.4; 95% CI:
      1.7-11.6). Likelihood of bleeding was substantially but not significantly
      increased (OR: 4.6; 95% CI: 0.3-83.9) with H. pylori seropositivity. These
      findings suggest that coxibs are a safer alternative than traditional NSAIDs in
      the treatment of haemophilic arthropathy.

PMID- 17498078
TI  - Evaluation of the oral health situation of a group of Egyptian haemophilic
      children and their re-evaluation following an oral hygiene and diet education
      programme.
AB  - Haemophilic children in Egypt have received minimal dental intervention and their
      dental needs required assessment. The purpose of this study was to assess the
      oral health needs of a sample (n = 60) of Egyptian haemophilic children (6-12
      years), so as to develop, implement and evaluate an oral hygiene education
      programme over an 8-month period on the experimental group (n = 30) vs. the
      control group (n = 30). The oral hygiene index simplified (OHI-S) index was used
      for baseline data and at the end of the study, while DMFS and defs were used to
      collect caries experience baseline data on each subject. The results showed that
      the DMFT and deft were significantly higher than those of the non-haemophilic
      population in Egypt and also higher than those of haemophilic children in
      developed countries and that the decayed component represented most of the index
      values. At phase I, the mean value of the OHI-S of experimental and the control
      groups was 2.67 +/- 0.45 and 2.53 +/- 0.53, respectively, but the difference was
      not significant (P > 0.05), both values were in the 'fair' category (1.3-3.0). At
      phase II, the end of the 8 months follow-up period and after the application of a
      strict oral care programme in the experimental group, there was a significant
      decrease from 2.67 to 1.20 (P < 0.001), a shift of values occurred from the
      'fair' category to the 'good' category (0.1-1.2) while there was no significant
      difference in the control group. It can be concluded that professional plaque
      control, education and access to oral hygiene aids is paramount to improve oral
      health of these children.

PMID- 17498079
TI  - Sonography for assessment of haemophilic arthropathy in children: a systematic
      protocol.
AB  - Radiological imaging of joints in children with haemophilia is important to
      detect abnormalities, grade their severity and monitor the effects of treatment.
      Scoring systems for staging haemophilic arthropathy have been developed based on
      plain film or magnetic resonance imaging (MRI) findings. Radiographs alone may be
      inadequate for evaluating joint disease in children with haemophilia on
      prophylaxis while MRI may be difficult to access and require the child to be
      sedated. Sonography can be a useful complementary modality in the evaluation of
      haemophilic arthropathy that is readily available and does not require the child
      to be sedated. In this paper, we briefly review the current imaging scales
      available for the assessment of haemophilic arthropathy and present a systematic
      protocol for sonographic assessment of the knee and ankle in haemophilic children
      along with examples of findings in joint effusion/hemarthrosis, synovial
      hypertrophy and cartilage loss. Also, we correlate the ultrasound findings with
      the corresponding MRI images demonstrating the anatomic planes used for imaging
      acquisition. Sonography is a promising technique for the assessment of soft
      tissue changes which are the earliest findings in haemophilic arthropathy.
      Further investigation is required for evaluation of osteochondral changes given
      limitations of sonography in this regard and in minimizing operator dependency,
      especially if applied in multicentric clinical trials.

PMID- 17498080
TI  - Psychological aspects and coping styles of parents with Haemophilic child
      undergoing a programme of counselling and psychological support.
AB  - Parents of children affected by haemophilia must face, often without prior
      knowledge, the difficult challenge imposed by such a pathology. To satisfy the
      need of information, guideline and psychological support for a better quality of
      life, 30 parents with haemophiliac children have participated in a programme of
      counselling and psychological support. Such a programme has the aim of guiding
      the group trough a process of discovery, comparison and personal growth and
      stimulating adaptive processes of problem-solving and decision-making. The aim of
      this paper was to verify how the programme influenced coping strategies and other
      psychological constructs such as depression and anxiety. Subjects of this study
      were administered the following psychological tests: COPE (coping, orientation to
      problems experienced), BDI (beck depression inventory), STAI-Y form (state-trait
      anxiety inventory) at the beginning and at the end of the programme. The results
      show that by the end of the programme subjects are characterized by a greater use
      of problem-focused coping strategies, typical of individuals who think that the
      situation is susceptible to change, and a minor use of emotion-focused coping
      strategies, related to individuals who regard the situation as immutable. The use
      of avoidance -focused coping strategies seems to remain at the same level even if
      it was low. Also the other psychological aspects investigated, namely depression
      and anxiety, did receive a positive influence. The results show how significant
      such programme has been for parents.

PMID- 17498081
TI  - Spectrum of mutations in Albanian patients with haemophilia A: identification of
      ten novel mutations in the factor VIII gene.
AB  - Genetic analysis was carried out in 37 Albanian patients with haemophilia A. The
      factor VIII intron 22 inversion was detected only in 2/19 (10.5%) apparently
      unrelated patients with severe haemophilia A, while the intron 1 inversion was
      absent. A total of 19 different gene mutations were identified. Ten mutations
      were novel: four null mutations in severe haemophilia A patients (Gln1090X,
      Cys1832X, 2374delT, 5676insT) and six missense mutations (five in severe
      haemophilia A) (Ile76Thr, Leu299Pro, Asp525Glu, Cys692Tyr, His1755Leu and
      Trp1835Cys). None of these novel mutations occurred at CpG hotspots. These
      results further emphasize the extreme heterogeneity of the molecular basis of
      haemophilia A. The low prevalence of intron 22 inversion in Albanian patients
      with severe haemophilia A should be addressed by further studies.

PMID- 17498082
TI  - ELISA system for detection of immune responses to FVIII: a study of 246 samples
      and correlation with the Bethesda assay.
AB  - Inhibitors of FVIII are usually IgG polyclonal antibodies that develop as
      alloimmune responses in patients with congenital haemophilia A or as autoimmune
      responses resulting in acquired haemophilia. Their recognition can be difficult,
      especially when the titre is low. Furthermore, results from a Bethesda assay
      often require several days as samples are referred to a specialty laboratory. The
      aim of this study is to assess the utility of an ELISA system for detecting
      immune responses to FVIII. A total of 246 plasma samples submitted from 176
      individuals with immune responses to FVIII, as verified with the Bethesda assay,
      and samples from 50 control subjects were tested for the presence of FVIII
      specific IgG using an ELISA-based assay. Paired sera from 18 of the patients were
      also tested by the ELISA. Of the 246 samples that were positive for a FVIII
      inhibitor by the Bethesda assay, 235 (95.5%) were also positive by ELISA. The
      regression coefficient, using Log BU was r = 0.82. The correlation data were
      strengthened when 27 inhibitor samples were diluted further. There was a strong
      correlation between ELISA results for the 18-paired serum and plasma samples (r =
      0.99). There is a strong correlation between the ELISA and Bethesda methods in
      detecting immune responses to FVIII. The ELISA provides rapid screening that
      could be available well in advance of confirmation by the Bethesda assay.

PMID- 17498083
TI  - Participation in sports and physical activity of haemophilia patients.
AB  - Modern therapy options offer haemophiliacs more and more possibilities for an
      active participation in sports. The purpose of the present study was to
      investigate the attitude of these patients towards sports, their participation in
      school and leisure time sports activities, and differences between juveniles and
      adults. We investigated 44 children and adolescents (aged from 4 to 16 years) and
      27 adults (aged from 18 to 72 years) with haemophilia by means of a
      questionnaire. 79.6% of the juvenile patients participated always or almost
      always in school sports, while this percentage was significantly (P < 0.05) lower
      in the former school time of the adults (37%). Sports play an important or very
      important role in leisure time activities for 75% of the adolescent and 55.5% of
      the adult haemophiliacs (P < 0.05). Bleeding complications occurred in 17.6% of
      all patients; there was no correlation with any particular type of sports. There
      were only slight differences between both groups, regarding their motivation to
      participate in sports activities. The main reasons involved social aspects and
      having fun. The results show that the modern therapy of haemophilia probably
      leads to a more positive attitude towards sports and to a wider spectrum of
      practised sports. This, however, may be associated with an increasing potential
      of health risks, which require a high level of sports medical care.

PMID- 17498084
TI  - Achievement of immune tolerance in a patient with haemophilia B and inhibitory
      antibodies, complicated by an anaphylactoid reaction.
AB  - We describe a young boy with severe haemophilia B who developed inhibitory
      antibodies and an anaphylactoid reaction to factor IX. Immune tolerance was
      achieved by desensitisation with escalating doses of factor IX followed by the
      Malmo regimen.

PMID- 17498085
TI  - Identification of factor VIII gene mutations and carrier detection in Korean
      haemophilia A patients.

PMID- 17498086
TI  - Severe factor X deficiency in a pair of siblings: clinical presentation,
      phenotypic and genotypic features, prenatal diagnosis and treatment.

PMID- 17498087
TI  - Fractures of long bones in severe haemophilia.

PMID- 17498088
TI  - Reduced bone density in individuals with combined factor V and VIII deficiency.

PMID- 17498090
TI  - In the end, "sex is complicated".

PMID- 17498092
TI  - Key Methodological Issues in Sexual Medicine Research.
AB  - The field of research in sexual medicine has grown dramatically in the past
      decade to a point where we now have a substantial armamentarium of pharmacologic
      and psychological interventions available for the treatment of sexual
      dysfunctions in men. Concomitantly, numerous new compounds are in advanced stages
      of clinical development to expand the spectrum of treatment options for women's
      sexual dysfunctions as well. We believe we have reached a point in our overall
      research agenda where it may be useful to reappraise certain aspects of our
      clinical research methodology. We have performed this with a view toward
      identifying a number of key issues that we believe represent continuing
      impediments to sustained growth in sexual medicine research, and we have made
      recommendations concerning implementing tactics and strategies that we believe
      will help overcome these methodological barriers to continued progress. We do not
      view the suggestions made here as definitive resolutions to the problems
      identified, but rather as progressive ideas that will enable our research to
      continue to move forward.

PMID- 17498093
TI  - Penile rehabilitation should become the norm for radical prostatectomy patients.
AB  - INTRODUCTION: The Journal of Sexual Medicine (JSM) held a debate at the annual
      fall meeting of the Sexual Medicine Society of North America (SMSNA). The motion
      was "Penile Rehabilitation Should Become the Norm for Radical Prostatectomy
      Patients." At the suggestion of several SMSNA members, it was requested that this
      debate might be of interest to JSM readers in the form of a published
      controversy. METHODS: Two debate speakers with expertise and/or strong opinions
      in the area of penile rehabilitation submitted their literature-review, evidence
      based opinions on the topic. MAIN OUTCOME MEASURE: Literature review of
      laboratory basic science and clinical research studies on penile rehabilitation.
      RESULTS: Penile rehabilitation involves prophylactic procedures designed to
      improve oxygen delivery to penile erectile tissues, aimed at preserving erectile
      tissue health and minimizing erectile tissue damage that otherwise occurs during
      the period of neural recovery to the autonomic cavernosal nerve following radical
      prostatectomy. There are several studies in the sexual medicine literature on
      penile rehabilitation after radical prostatectomy, and the positive results
      appear to support this concept, the rationale, and mechanism. The use of
      prophylactic penile rehabilitation programs has not been fully elucidated, nor
      have the results been replicated in large multicenter placebo-controlled trials.
      CONCLUSION: Penile rehabilitation may be performed along with counseling with the
      couple, vacuum erection therapy, and vacuum erection device therapy if it is the
      patient and partner's preference, provided that it is undertaken in a safe and
      effective manner and is monitored closely.

PMID- 17498095
TI  - Z-plasty reductional labiaplasty.

PMID- 17498096
TI  - The politics of testosterone.

PMID- 17498097
TI  - Canadian Society for the Study of the Aging Male: response to health Canada's
      position paper on testosterone treatment.
AB  - INTRODUCTION: Testosterone treatment of older symptomatic men with reduced
      testosterone availability is increasing. There is an expanding body of literature
      to support such treatment in a large subset of aging men, but there has not yet
      been a long-term placebo-controlled double-blind study of several thousand men to
      confirm the efficacy and safety of this treatment as indicated by shorter-term
      studies. The absence of a long-term study has been used by governmental agencies
      as a limiting factor in providing full access and payment for this treatment in
      government-sponsored health care plans. Health Canada issued a testosterone
      analysis document to the pharmaceutical industry, the implications of which may
      make it more difficult for appropriate patients to receive such treatment. The
      Canadian Society for the Study of the Aging Male (CSSAM) believed it had an
      obligation to advocate on behalf of men requiring this treatment. AIM: To provide
      an international consensus on the use of testosterone treatment in appropriately
      selected hypogonadal men. MAIN OUTCOME MEASURE: To determine whether the
      literature supports the use of testosterone treatment in a selected population of
      hypogonadal men, to achieve consensus on this point among an international
      consulting group, and to transmit this view to health care workers and insuring
      and governmental agencies. METHODS: Email communication among the consulting
      group to prepare a response to Health Canada, followed by a review of appropriate
      literature and international practice guidelines, incorporating the literature
      and guidelines together with the CSSAM letter and Health Canada's response.
      RESULT: The literature and international guidelines support the initiation of
      testosterone therapy in symptomatic hypogonadal men, recognizing that there is no
      universal agreement on the criteria for the diagnosis of hypogonadism in each
      suspected case. The need for careful monitoring of such men is stressed.
      CONCLUSION: CSSAM acted as an advocate for hypogonadal men who may benefit from
      treatment with testosterone. Short-term studies and 60 years of experience with
      testosterone therapy attest to its efficacy. Long-term studies are desirable, but
      it may take many years before results could be forthcoming. There is no evidence
      to suggest that testosterone treatment increases the risk of prostate cancer or
      cardiovascular disease. Current evidence suggests, in fact, that testosterone
      treatment may be cardioprotective. It is important to bring this information to
      the attention of governments and insuring agencies through the collaboration of
      groups devoted to the diagnosis and treatment of hypogonadal men.

PMID- 17498098
TI  - The prevalence of erectile dysfunction among hypertensive and prehypertensive men
      aged 25-40 years.
AB  - INTRODUCTION: Erectile dysfunction (ED) and hypertension (HTN) are common and
      associated among men aged 40-70 years. Data on the prevalence of ED among younger
      hypertensive and prehypertensive men are limited. AIM: To study the prevalence of
      ED in a large-scale population of hypertensive and prehypertensive men aged 25-40
      years. MAIN OUTCOME MEASURES: ED severity, systolic blood pressures (SBPs),
      diastolic blood pressures (DBPs), and mean arterial blood pressures (MAPs).
      METHODS: Israel Defense Force personnel, aged 25 years and older, go through
      routine health checks at the Staff Periodic Health Examination Center (SPEC)
      every 3-5 years, including measuring blood pressure and completing the Sexual
      Health Inventory for Men (SHIM) questionnaire in order to detect HTN and ED,
      respectively, and assess its severity. Pre-HTN was defined as SBP 120-139 mm Hg
      or DBP 80-89 mm Hg. HTN was defined as SBP >/or140 mm Hg and/or DBP >or=90 mm Hg.
      RESULTS: During 2001-2004, an overall of 11,252 men, aged 25-40 years, reported
      to the SPEC, and 5,860 (52.1%) men filled out the SHIM questionnaire. Among
      responders to the SHIM questionnaire, 1,278 (21.8%) men had low scores (<or=21),
      suggesting ED. Overall, 3021 (51.6%) men had pre-HTN and 557 (9.5%) men had HTN.
      The prevalence of ED was similar among men with HTN, men with pre-HTN, and men
      with normal blood pressure: 22.9% vs. 21.3% vs. 22.3%, respectively. In addition,
      SBPs, DBPs, and MAPs were not associated with the SHIM scores among all men.
      CONCLUSIONS: The prevalence of ED is not increased among hypertensive and
      prehypertensive men compared with normotensive men aged 25-40 years. Moreover,
      higher blood pressures are not associated with worse erections among all men in
      this age group. Apparently, it takes years for HTN to cause ED.

PMID- 17498099
TI  - Immunohistochemical description of cyclic nucleotide phosphodiesterase (PDE)
      isoenzymes in the human labia minora.
AB  - INTRODUCTION: Up until now, only minimal research has been carried out on those
      female genital organs known to contribute to the normal cycle of sexual arousal
      and orgasm. Some findings indicated that there might be a significance of cyclic
      nucleotide-mediated pathways in the control of the normal function of female
      genital tissues. AIM: To elucidate, by means of immunohistochemistry, the
      distribution of the phosphodiesterase (PDE) isoenzymes 1, 3, 4, 5, 10, and 11 in
      the human labia minora. MAIN OUTCOME MEASURES: The amount of immunohistochemical
      staining specific for cyclic adenosine monophosphate (cAMP)- and/or cyclic
      guanosine monophosphate (cGMP)-degrading PDE isoenzymes was detected. METHODS:
      Human labial tissue was obtained from four female cadavers (age at death: 18-42
      years). Vibratome sections prepared from formaldehyde-fixated tissue specimens
      were incubated with primary antibodies directed against the respective PDE
      isoenzymes. Sections were then incubated with fluorochrome (fluorescein
      isothiocyanate, Texas Red)-labeled secondary antibodies. Visualization was
      commenced by means of a laser fluorescence microscope. RESULTS: Immunostaining
      indicating the expression of PDE4 and PDE5 was abundantly observed in the smooth
      musculature of vessels interspersing the tissue. Immunoreactions specific for
      PDE3 were recognized in epithelial and subepithelial layers, sebaceous glands,
      and interstitial or neuroendocrine-like single cells located in the epithelium.
      Signals related to PDE10 and PDE11 were limited to the epithelium or glandular
      like structures, respectively. CONCLUSIONS: Our results, for the first time,
      demonstrate the presence of cAMP- and cGMP-PDE isoenzymes in the human labia
      minora and give a hint to a significance of PDE4 and PDE5 in the control of
      labial vascular tissue function.

PMID- 17498100
TI  - Testosterone increases blood flow and expression of androgen and estrogen
      receptors in the rat vagina.
AB  - INTRODUCTION: The mechanisms by which testosterone modulates female genital
      sexual arousal responses are poorly understood. AIM: To investigate the effects
      of testosterone on vaginal blood flow and the expression of estrogen and androgen
      receptor proteins in the rat vagina. METHODS: Mature female Sprague-Dawley rats
      were sham-operated (intact) or ovariectomized. Fourteen days after ovariectomy,
      animals were continuously infused with vehicle or varying doses of testosterone
      (5.5-55 microg/day). After 2 weeks of treatment, vaginal blood flow in response
      to pelvic nerve stimulation was measured by laser Doppler flowmetry. Plasma
      levels of testosterone and estradiol were determined by radioimmunoassay and
      epithelial thickness was examined in fixed vaginal tissue sections. Androgen and
      estrogen receptor levels were assessed by equilibrium radioligand binding and by
      Western blot analyses. RESULTS: Vaginal blood flow responses were significantly
      reduced in ovariectomized rats and normalized in animals infused with
      testosterone. Ovariectomy increased the expression of estrogen receptors and
      reduced the expression of androgen receptors with no change in receptor-ligand
      affinity. Testosterone increased the expression of both androgen and estrogen
      receptors in the vagina. While physiological (11 microg/day) and
      supraphysiological (55 microg/day) concentrations of testosterone normalized
      vaginal tissue weight, uterine tissue and whole body weights were not
      significantly different from ovariectomized rats infused with vehicle.
      Testosterone infusion, even at supraphysiological concentrations, did not change
      plasma estradiol levels when compared to vehicle-infused, ovariectomized rats.
      Likewise, the vaginal epithelium of testosterone-infused rats remained atrophic,
      similar to vehicle-infused, ovariectomized rats, indicating that testosterone is
      not aromatized to estrogens at significant levels in the vagina. CONCLUSIONS: Our
      data suggest that testosterone regulates androgen and estrogen receptor protein
      expression in the vagina and enhances vaginal perfusion by an androgen-dependent
      mechanism. We conclude that testosterone plays an important role in modulating
      the physiology of the vagina and contributes to improvement of genital sexual
      arousal responses.

PMID- 17498101
TI  - Testosterone regulates RhoA/Rho-kinase signaling in two distinct animal models of
      chemical diabetes.
AB  - INTRODUCTION: The contractile RhoA/Rho-kinase (ROCK) signaling pathway is
      upregulated in penile tissue in animal models of experimental diabetes and has
      been proposed to contribute to diabetes-related erectile dysfunction (ED). AIM:
      To investigate the effect of testosterone (T) on the RhoA/ROCK signaling in
      diabetes. METHODS: We used two distinct animal models of chemical diabetes
      (alloxan-induced in the rabbit and streptozotocin-induced in the rat) with or not
      T supplementation. MAIN OUTCOME MEASURES: The effect of diabetes and T
      supplementation on RhoA/ROCK signaling was evaluated as responsiveness to the
      selective ROCK inhibitor Y-27632 either by "in vitro" contractility study
      (diabetic rabbit) or "in vivo" as erectile response elicited by intracavernous
      injections (diabetic rats). RhoA/ROCK gene and protein expression were also
      analyzed. RESULTS: In both models, hypogonadism was observed, characterized by
      reduced T plasma level and androgen-dependent accessory glands atrophy. Diabetic
      animals showed a significant increase in responsiveness to increasing
      concentrations of Y-27632. T substitution (30 mg/kg, weekly) completely prevented
      hypogonadism and diabetes-induced penile hypersensitivity to Y-27632. To test
      whether this effect was due to a T-dependent regulation of RhoA/ROCK gene
      expression, we measured RhoA/ROCK mRNA. Both isoforms of ROCK (ROCK1/ROCK2) were
      analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in
      rat penile samples. We found that ROCK1 mRNA was significantly increased (P <
      0.05) in penile tissues from diabetic animals and maintained at the control
      values by T, as also confirmed by semiquantitative RT-PCR in rabbit. Conversely,
      RhoA and ROCK2 mRNA expression was not influenced either by diabetic condition or
      by T administration. Accordingly, ROCK1 protein expression, as evaluated by
      Western blot and immunohistochemistry analysis, was increased in penile samples
      from diabetic animals and normalized by T. CONCLUSIONS: Our data further support
      the hypothesis that the overexpression of RhoA/ROCK signaling contributes to
      diabetes-related ED. Moreover, treating hypogonadism in course of diabetes may
      maintain erectile function also by normalizing RhoA/ROCK pathway upregulation.

PMID- 17498102
TI  - A three-dimensional theoretical model of the relationship between cavernosal
      expandability and percent cavernosal smooth muscle.
AB  - INTRODUCTION: Percent corporal smooth muscle content, a traditional predictor of
      corporal veno-occlusive function, is invasive and clinically assessed by
      histomorphometric analyses of erectile tissue biopsies. Cavernosal
      "expandability" which may be a more physiologically relevant parameter is a
      measure of work performed to achieve penile erection, and as a consequence, an
      indicator of the ability to approach maximum penile volume at low intracavernosal
      pressure. AIM: To demonstrate that cavernosal "expandability" determined by
      noninvasive methodology can replace the determination of percent smooth muscle.
      To predict Young's modulus for the corpora cavernosa in rabbits and, this by
      inference, in humans; the latter facilitates the comparison of resistance to
      penile expansion presented by the tunica vs. cavernosal tissue. MAIN OUTCOME
      MEASURE: A refined three-dimensional formula for cavernosal expandability,
      defined as the negative reciprocal of the cavernosal bulk modulus in the
      semierect state, was derived as a function of percent corporal smooth muscle
      content, using principles of engineering mechanics of materials. The model
      included Young's modulus, E, for the corpora cavernosa as an unknown parameter.
      METHODS: Volume-pressure data obtained from three groups of New Zealand white
      rabbits: (i) control group (N = 7); (ii) hypercholesterolemic group (N = 5) on
      0.5%; (iii) atherosclerotic group (N = 8), was plotted, and compared with the
      model. RESULTS: Data points of mean cavernosal expandability (0.012-0.017 (mm
      Hg)(-1)) vs. percent trabecular smooth muscle content (33.9-45.4%) for the three
      groups of rabbits were analyzed. The revised model formula was fitted to the
      existing rabbit experimental data points producing a value of Young's modulus
      equal to 0.01 (MPa). CONCLUSIONS: Rabbit cavernosal expandability can predict
      percent smooth muscle content. Cavernosal Young's modulus can be predicted.
      Further clinical research efforts to provide human data are needed.

PMID- 17498103
TI  - Overactive bladder and women's sexual health: what is the impact?
AB  - INTRODUCTION: Overactive bladder (OAB) is quite prevalent and significantly
      affects health-related quality of life and daily functioning. AIM: The impact of
      OAB on sexual health is currently not known. This qualitative study was conducted
      to gain a thorough understanding of OAB's impact. METHODS: Sexually active women
      with continent or incontinent OAB were recruited from urology and urogynecology
      clinics. Six focus groups of women (three continent and three incontinent) were
      conducted to assess the sexual health of women with OAB. Data were analyzed
      descriptively and qualitatively. MAIN OUTCOME MEASURES: Qualitative data, Sexual
      Quality of Life Questionnaire-Female, Overactive Bladder Questionnaire. RESULTS:
      Thirty-four women (11 continent; 23 incontinent) participated; mean age was 48.4
      years; 76% were white, 67% postmenopausal, and 88% in a long-term relationship.
      Continent women reported more frequent sexual activity than incontinent women;
      91% reported intercourse >or=1-3 times per month vs. 50% of incontinent women.
      Half of the incontinent women reported a reduction in sexual desire related to
      OAB, aging, and menopause. Over half of continent women experienced pain with
      intercourse, and the majority complained of having to interrupt intercourse to
      void. Although not all incontinent women reported incontinence during
      intercourse, the majority were embarrassed by their incontinence and OAB with
      resulting loss of self-image. Both continent and incontinent women reported
      difficulty achieving orgasm because of pain, fear of incontinence, or anxiety
      related to intercourse. Approximately a third of the women would not initiate
      discussion of sexual issues with their physicians, but all women expressed
      concern about the impact of OAB on their sexual life. CONCLUSION: Overactive
      bladder with or without incontinence negatively affects women's sexual health,
      reducing sexual desire and ability to achieve orgasm. Given the impact of OAB on
      sexual health, sexual health should be routinely assessed by clinicians and
      addressed by researchers.

PMID- 17498104
TI  - Electrophysiologic activity of the tunica albuginea and corpora cavernosa:
      possible role of tunica albuginea in the erectile mechanism.
AB  - INTRODUCTION: It is claimed that the tunica albuginea (TA) shares in the erectile
      mechanism by compressing the emissary veins passing through it. However, the TA
      does not contain smooth muscle fibers. AIM: We investigated the hypothesis that
      TA lacks a contractile activity on the emissary veins passing through it.
      METHODS: Fourteen healthy male volunteers (mean age 35.2 +/- 4.3 years) were
      studied. The electromyographic (EMG) activity of the TA and corpora cavernosa
      (CC) was individually recorded in the flaccid and erectile phases by EMG needle
      electrodes. Recording was performed in the upper, middle, and lower third of the
      TA and CC on one and then on the contralateral side. MAIN OUTCOME MEASURES: The
      TA lacks a contractile activity on the emissary veins passing through it.
      RESULTS: The EMG of the CC in the flaccid phase recorded regular slow waves and
      random action potentials. The wave variables in the erectile phase exhibited a
      significant decrease (P < 0.01) compared with the variables in the flaccid phase
      of the same subject. The TA EMG showed no electric waves in the flaccid or
      erectile phases. These recordings were similar from the upper-, middle-, and
      lower-third of the penis, and were reproducible from the contralateral CC.
      CONCLUSIONS: Electric waves were recorded from the CC in the flaccid phase; wave
      variables decreased at erection. In contrast, the TA showed no electric waves in
      the flaccid or erectile phases. It appears that the TA acts as a CC covering
      sheet which expands passively at erection, and shares in compressing the
      subtunical venular plexus between it and the tumescent CC.

PMID- 17498105
TI  - Persistent genital arousal: disordered or normative aspect of female sexual
      response?
AB  - INTRODUCTION: Persistent genital arousal disorder (PGAD), previously known as
      persistent sexual arousal syndrome, is a serious and extremely distressing
      condition. Clinical experience suggests that there may be a subset of women who
      experience persistent genital arousal as a normative and not especially
      distressing part of their sexuality. AIM: To determine whether there are women
      who report unprovoked genital arousal and view it as normative, and to identify
      differences between women who endorse all five features of PGAD vs. those who
      endorse only some of features. MAIN OUTCOME MEASURES: Respondents were asked
      about the nature, onset, duration, and severity of their arousal, and their
      feelings about PGAD. Overall sexual and relationship satisfaction was assessed,
      as were scores on the Female Sexual Function Index (FSFI). METHODS: An on-line,
      anonymous survey on persistent genital arousal was conducted. Of the 388
      respondents, 206 women endorsed all five features of PGAD (PGAD group) and 176
      endorsed some, but not all, criteria (non-PGAD group). RESULTS: The two groups
      were similar in age, relationship status, and duration. More PGAD than non-PGAD
      women reported current symptoms and greater symptom severity. Distress ratings
      were significantly greater for PGAD than non-PGAD women (7.9 vs. 4.7 on a 10
      point scale). Forty-eight percent of PGAD vs. 27% of non-PGAD women reported
      continuous feelings of arousal. Significantly more PGAD women than non-PGAD women
      endorsed negative feelings about their genital arousal. Women with PGAD reported
      lower desire, less sexual satisfaction, greater pain, and lower overall scores on
      the FSFI. CONCLUSIONS: There is a cohort of women who regularly, if
      intermittently, experience unprovoked and persistent genital arousal and find it
      mildly pleasurable. Their genital arousal differs from that of women who meet all
      five criteria for a diagnosis of PGAD. Possible explanations and etiologies for
      these differing reactions are discussed.

PMID- 17498106
TI  - Women's endorsement of models of female sexual response: the nurses' sexuality
      study.
AB  - INTRODUCTION: The current Summary of Recommendations on Sexual Dysfunction in
      Women is conceptually grounded on a model of women's sexual function that has not
      been empirically tested in samples of women with and without sexual dysfunction.
      AIM: The current research represents an initial effort to assess the extent to
      which women in a community sample endorse current theoretical models of female
      sexual function based upon work by Masters and Johnson, Kaplan, and Basson as
      accurately reflecting their own sexual experience. MAIN OUTCOME MEASURES: Women's
      endorsement of brief descriptions of current models of female sexual function
      (Masters and Johnson, Kaplan, and Basson) as accurately reflecting their own
      sexual experience and their own levels of sexual function or dysfunction as
      assessed by the Female Sexual Function Index (FSFI). METHODS: A random sample of
      580 Registered Nurses was mailed a 58-item questionnaire which assessed women's
      perception of the fit of their sexual experience with current models of female
      sexual response and included the FSFI. RESULTS: In total, 133 women, of whom 111
      had a current man partner, returned responses. Approximately equal proportions of
      women endorsed the Masters and Johnson, Kaplan, and Basson models of female
      sexual response as representing their own sexual experience. Women endorsing the
      Basson model had significantly lower FSFI domain scores than women who endorsed
      either the Masters and Johnson or Kaplan models. CONCLUSION: These are the first
      data to assess the proportion of a community sample of women who endorse widely
      accepted models of female sexual response as representing their own sexual
      experience. Women in this sample were equally likely to endorse each of these
      different models, emphasizing the heterogeneity of women's sexual response, and
      highlighting the need for additional research to guide the field's acceptance and
      application of particular models of female sexuality in particular situations.
      Women's endorsement of models of female sexual response was correlated with their
      FSFI scores, and findings suggest that the Basson model, currently advanced by
      the Second International Consultation on Sexual Medicine, may best reflect women
      with sexual concerns (e.g., FSFI < 26.55), rather than a single normative sexual
      response pattern.

PMID- 17498107
TI  - Interstitial cystitis/painful bladder syndrome as a cause of sexual pain in
      women: a diagnosis to consider.
AB  - INTRODUCTION: Sexual pain, or dyspareunia, is a common symptom among women.
      Dyspareunia presents in many ways, and arises from a range of causes.
      Interstitial cystitis/painful bladder syndrome (IC/PBS) is one potential cause
      that may frequently be overlooked by clinicians. Interstitial cystitis is
      increasingly recognized as more common than was once thought. However, it can be
      difficult to identify, as the symptoms of IC/PBS (urinary urgency and frequency,
      dyspareunia, nocturia, and pelvic pain) overlap with other urogynecologic
      conditions. AIM: This article will review the association between dyspareunia and
      IC/PBS, and will provide an approach to the diagnosis and treatment of IC/PBS in
      women with sexual pain. METHODS AND MAIN OUTCOME MEASURES: Review of the medical
      literature and expert medical opinion. RESULTS: Many women with IC/PBS experience
      dyspareunia, often in conjunction with chronic pelvic pain. When IC/PBS is
      suspected, there are simple measures to aid in the diagnosis of this condition,
      and treatments are readily available. CONCLUSIONS: When a woman presents with the
      symptoms of urinary urgency and frequency, dyspareunia, nocturia, and/or pelvic
      pain, IC/PBS should be part of the diagnostic evaluation.

PMID- 17498108
TI  - The efficacy and safety of vardenafil in East Asian men with erectile
      dysfunction.
AB  - INTRODUCTION: Previous clinical studies assessing the efficacy and safety of
      vardenafil, an oral phosphodiesterase type 5 inhibitor, in men with erectile
      dysfunction (ED) have consisted mostly of Caucasian patients. AIM: The aim of
      this article is to describe the efficacy and safety of vardenafil in men of East
      Asian ethnicity with ED. METHODS: Data were pooled from two 12-week, double-blind
      studies that included 306 East Asian men randomized to placebo or 10 mg of
      vardenafil. MAIN OUTCOME MEASURES: Efficacy variables included the International
      Index of Erectile Function-erectile function (IIEF-EF) domain score,
      questionnaires of Sexual Encounter Profile (SEP2 and SEP3), and a Global
      Assessment Question (GAQ). Safety assessments included laboratory tests, vital
      signs, 12-lead electrocardiogram recordings, and patients' reporting of adverse
      events. RESULTS: A total of 306 East Asian men with ED were treated with placebo
      (N = 151) or vardenafil (N = 155). Mean baseline IIEF-EF domain scores (placebo,
      13.4; vardenafil, 14.2) were consistent with moderate ED. At end point, the
      patients treated with vardenafil had a significantly greater increase in IIEF-EF
      domain score compared with placebo (24.2 vs. 15.9; P < 0.0001). The average per
      patient penetration (SEP2) success rate was significantly higher in the
      vardenafil group compared with placebo (88% vs. 58%; P < 0.0001). Moreover, the
      average per patient intercourse completion (SEP3) success rate was significantly
      higher in the vardenafil group compared with placebo (69% vs. 23%; P < 0.0001).
      Positive GAQ responses were reported by 85% of patients receiving vardenafil,
      compared with 33% of those receiving placebo. The most frequent adverse events
      were vasodilatation (primarily facial flushing), rhinitis, and headache, all of
      which were of mild intensity. CONCLUSIONS: Vardenafil is an effective, well
      tolerated oral drug for the treatment of East Asian men with moderate ED of broad
      spectrum etiology.

PMID- 17498109
TI  - A comparison of NCEP-ATPIII and IDF metabolic syndrome definitions with relation
      to metabolic syndrome-associated sexual dysfunction.
AB  - INTRODUCTION: Metabolic syndrome (MetS) is a clustering of cardiovascular and
      metabolic risk factors, often associated with erectile dysfunction (ED) and
      hypogonadism. Recently, the International Diabetes Federation (IDF) proposed a
      substantial revision of the National Cholesterol Education Program-Third Adult
      Treatment Panel (NCEP-ATPIII) MetS criteria, essentially lowering the diagnostic
      cutoff values. Aim. To investigate the associations between these two recently
      proposed definitions of MetS with the relative risk of arteriogenic ED and
      hypogonadism in a large cohort of patients with male sexual dysfunction. METHODS:
      A consecutive series of 1086 patients with sexual dysfunction (mean age 51.9 +/-
      12.8 years) was studied. MAIN OUTCOME MEASURES: Several hormonal, biochemical,
      and instrumental (penile Doppler ultrasound) parameters were studied, along with
      ANDROTEST, a 12-item validated structured interview, specifically designed for
      the screening hypogonadism in a sexual dysfunction population. In particular, a
      score >8 is predictive of low testosterone (<10.4 nmol/L) with a sensitivity and
      specificity of about 70%. RESULTS: The prevalence of MetS was 32.0% and 44.7%
      according to NCEP-ATPIII and IDF criteria, respectively. After adjustment for
      confounding factors, only NCEP-ATPIII was significantly associated with dynamic
      prostaglandin E(1)-stimulated penile flow (Vpmax, B = -7.7 +/- 3.8; P < 0.05).
      Patients with MetS defined according to both criteria reported lower total and
      free testosterone levels, higher prevalence of hypogonadism, and higher ANDROTEST
      score. However, when IDF, but not NCEP-ATPIII, criteria were fulfilled, the
      prevalence of hypogonadism was significantly lower than that observed in patients
      fulfilling both criteria (15.6% vs. 34.8%, respectively; P < 0.00001).
      Conversely, patients fulfilling NCEP-ATPIII, but not IDF, criteria did not show a
      significant different prevalence of hypogonadism than those positive for both
      sets of criteria (30.8% vs. 34.8%; P = NS). CONCLUSIONS: In patients with ED,
      NCEP-ATPIII criteria seem to be a better predictor of hypogonadism and impaired
      penile blood flow than IDF ones.

PMID- 17498110
TI  - Androgen deficiency and abnormal penile duplex parameters in obese men with
      erectile dysfunction.
AB  - INTRODUCTION: The clinical identification of metabolic syndrome is based on
      measures of abdominal obesity, atherogenic dyslipidemia, elevated blood pressure,
      and glucose intolerance. However, the impact of hypogonadism associated with
      obesity on penile hemodynamics is not well investigated. AIM: In this
      retrospective study, we sought to evaluate the effect of obesity on serum total
      testosterone (TT) level and penile duplex parameters in men with erectile
      dysfunction (ED). METHODS: Our participants (N = 158) were evaluated for erectile
      function using an abridged, five-item version of the International Index of
      Erectile Function-5. Determination of body mass index (BMI) was performed.
      Measurements of TT, fasting lipid profile, and blood sugar were conducted. Penile
      hemodynamics was assessed using intracavernosal injection and penile duplex
      study. MAIN OUTCOME MEASURES: Bivariate associations among BMI and serum
      testosterone, blood pressure, and lipid profile, as well as penile duplex
      parameters. We compared all clinical, laboratory, and penile duplex parameters
      between lean men (BMI < 25) and overweight and obese men (BMI >or= 25). RESULTS:
      The participants' age ranged between 20 and 56 years. A significant negative
      correlation between BMI and TT was detected (r = -0.431, P = 0.0001).
      Hypogonadism was identified in 54/158 (34.2%) of men with ED. The incidence of
      hypogonadism varied from as low as 1/18 (5.6%) in lean men to as high as 18/36
      (50%) to 21/35 (60%) in morbid and severe obesity, respectively. Vasculogenic ED
      was detected in 32/54 (59.3%) men with BMI >or= 25, compared with 5/18 (27.8%) in
      lean men (P = 0.029). In order to study the effect of obesity on erectile
      function, cases with other risk factors were excluded. Of 67 men suffering from
      ED with no other risk factor(s) apart from obesity, vasculogenic ED was detected
      in 32/54 (59.3%) men with BMI >or= 25, compared with 3/13 (23.1%) in lean men (P
      = 0.029). CONCLUSION: Obesity is associated with lower TT and disturbances of
      penile hemodynamics. It is an independent clinical factor for vasculogenic ED.

PMID- 17498111
TI  - The birth and development of sexual medicine: reflections of my personal journey.
AB  - INTRODUCTION: The phrase "sexual medicine" has become commonplace, as there is
      now the International Society for Sexual Medicine, the British Society for Sexual
      Medicine, the European Academy for Sexual Medicine, and the Journal of Sexual
      Medicine. The historic origin of the phrase "sexual medicine" is somewhat
      obscure. AIM: The goal of this report is to provide my own individual journey as
      a physician to recall the use of the phrase "sexual medicine." METHODS:
      Literature review, personal historic recall. RESULTS: Gorm Wagner has identified
      an early publication/journal article [corrected] in the German language from 1908
      that includes [corrected] "Sexualmedizin" in its title [corrected] Later journals
      between 1914 and 1933 are entitled "Sexualwissenschaft (Sexual Science)," but do
      not specifically use the term "Sexual Medicine" [corrected] I have no
      recollection of having heard the term "sexual medicine" before a meeting in 1970
      on nonconsummation. I met Dr. Eric Trimmer, editor of "Medical News," who
      discussed with me the idea of introducing a new journal devoted to sexual issues.
      I suggested the title "British Journal of Sexual Medicine." The term "sexual
      medicine" was preferred because it encompassed both organic and psychological
      issues of sexual function and its problems. The British Journal of Sexual
      Medicine was published in 1973 to 1985. Other titles using Sexual Medicine
      appeared in other texts over the years. CONCLUSIONS: From my perspective,
      including a search of the literature in the English language published in or
      before 1970 that failed to find any reference to sexual medicine, I conclude that
      the phase "sexual medicine" was popularized in the 1970s.

PMID- 17498112
TI  - The DSM-IV-TR Is an inadequate diagnostic tool for premature ejaculation.

PMID- 17498114
TI  - Is it time to revisit residual renal function in haemodialysis?
AB  - Residual renal function (RRF) is not currently emphasized for patients undergoing
      haemodialysis (HD). The role of RRF is well recognized in the peritoneal dialysis
      population as studies have clearly demonstrated a survival benefit with
      preservation of RRF. There is however, data to suggest that RRF is important in
      HD patients as well. Contemporary HD therapies using high flux biocompatible
      synthetic dialysers, bicarbonate buffered ultrapure dialysis fluids with
      ultrafiltration control appear to allow better preservation of RRF. The long held
      belief that peritoneal dialysis is better at preserving RRF than HD may no longer
      be true. More robust studies are required to determine the relative importance of
      RRF in HD and strategies to best preserve this vital asset.

PMID- 17498115
TI  - Baseline and time-averaged fluid removal affect technique survival in peritoneal
      dialysis in a non-linear fashion.
AB  - AIM: The longevity of peritoneal dialysis (PD) is limited by technique failure
      and patient mortality. The authors assessed the influence of baseline and time
      averaged fluid removal on patient, technique and death-censored technique
      survival. METHODS: Peritoneal and total fluid removal was measured 1 month after
      commencing PD, then 6 monthly, in 225 incident patients (mean age 55.3+/-15.8
      years, 52% male). A Cox proportional hazards model regression analysis was
      performed to identify variables independently predictive of technique and patient
      survival. RESULTS: Seventy (31.9%) patients were transferred to haemodialysis and
      39 (17.63%) died. Technique survival was greatest in the middle tertile of
      baseline total fluid removal (mean survival time 3.5 vs 2.5 and 2.2 years for the
      lower and upper tertiles, respectively, log rank 6.5, P=0.039). The middle
      tertile of both baseline and time-averaged total fluid removal were significant
      predictors of PD survival (adjusted hazard ratio (HR) 0.476, 95% CI 0.286-0.795,
      P=0.005 relative to the upper tertile and HR 0.573, 95% CI 0.350-0.939, P=0.027
      for baseline and time-averaged, respectively). Other significant variables on
      multivariate analysis were body mass index (HR 1.044 per kg/m2, 95% CI 1.005
      1.084, P=0.028), creatinine (HR 0.999 per micromol, 95% CI 0.998-1.000, P=0.048)
      and residual Kt/V (HR 0.418, 95% CI 0.233-0.747, P=0.003). Patient survival was
      not affected by fluid removal. CONCLUSION: Patients with moderate total fluid
      removal both at baseline and throughout their PD career have improved technique
      survival. Attention should be paid to optimizing total fluid removal.

PMID- 17498116
TI  - Mineral metabolism, bone histomorphometry and vascular calcification in alternate
      night nocturnal haemodialysis.
AB  - BACKGROUND: Poor control of bone mineral metabolism (BMM) is associated with
      renal osteodystrophy and mortality in dialysis-dependent patients. The authors
      explored the efficacy of alternate nightly home haemodialysis (ANHHD) in
      controlling BMM parameters and its effects on bone mineral density and
      histomorphometry. METHODS: In this prospective observational study, 26 patients
      on home haemodialysis (3-5 h, 3.5-4 sessions weekly) were converted to ANHHD (6-9
      h, 3.5-4 sessions weekly). Biochemical parameters of BMM at baseline, 6 and 12
      months, radiological parameters at baseline and 12 months and bone
      histomorphometry at 12 months are described. RESULTS: Pre-dialysis serum
      phosphate fell from 2.13+/-0.65 to 1.38+/-0.35 mmol/L; P<0.0001. No binders were
      required in 77.2% compared with 7.7% at baseline. Calcium-phosphate product fell
      from 5.28+/-1.64 to 3.42+/-0.88 mmol2/L2; P<0.0001 and parathyroid hormone (PTH)
      from 301 (110-471) to 127 (47-240) ng/L; P=0.01. Bone mineral density remained
      stable. Vascular and ectopic calcification improved or stabilized in 87.5%. Bone
      histomorphometry at 12 months showed high, normal and low bone turnover in 10, 3
      and 4 patients, respectively, with 6/17 patients having abnormal mineralization.
      CONCLUSION: Alternate nightly home haemodialysis effectively manages biochemical
      parameters of BMM. Patients with very high PTH at baseline (>1000 ng/L) did not
      significantly improve parathyroid hormone status. Abnormal bone turnover and
      mineralization were present in a significant proportion of patients at 12 months
      but low turnover was uncommon. Vascular calcification was stabilized or improved
      in the majority. ANHHD compares favourably with every night and short daily
      therapy in relation to BMM management and may offer lifestyle advantages for
      patients.

PMID- 17498117
TI  - Effect of pravastatin on markers of endothelial activation in dialysis patients.
AB  - AIM: The aim of this pilot study was to test the effect of pravastatin on serum
      levels of high-sensitivity CRP (hs-CRP), IL-6 and the soluble adhesion molecules
      sVCAM-1, sICAM-1 and sE-selectin in chronic dialysis patients. METHODS: At the
      commencement of the study, serum levels of lipids, liver function tests and
      endothelial markers (CRP, IL-6, sICAM-1, sVCAM-1, sE-selectin) were measured.
      Patients then commenced 1 month of 10 mg of pravastatin per day, and if
      tolerated, then 4 months of 40 mg of pravastatin per day. Serum levels of lipids,
      liver function tests and endothelial markers were repeated after the total of 5
      months of pravastatin therapy. RESULTS: Thirty-nine patients were enrolled, and
      25 (male/female 17/8; 21 haemodialysis, 4 peritoneal dialysis) patients completed
      the study. Pravastatin therapy significantly improved the patients' lipid
      profiles, but had no significant effect on the levels of CRP, IL-6, sICAM-1,
      sVCAM-1, or sE-selectin. CONCLUSION: Short-term (5 months) treatment with
      pravastatin in patients receiving chronic dialysis improved their lipid profile,
      but had no significant effect on surrogate markers of endothelial activation.

PMID- 17498118
TI  - Risk factors for peritoneal dialysis-related peritonitis: can we reduce the
      incidence and improve patient selection?
AB  - BACKGROUND: Peritonitis is a serious complication of peritoneal dialysis (PD) and
      a major cause of hospitalization, catheter loss, transfer to haemodialysis and
      death. Thus, it is important to identify risk factors for PD-related peritonitis
      in order to reduce the incidence and improve patient selection. METHODS: This
      study is a prospective cohort review (1992-2003) with data consisting of 12,844
      patient months, 506 PD patients and 623 episodes of peritonitis. Comorbidities
      and patient demographics were provided by the Australian and New Zealand Dialysis
      and Transplant Registry and these were merged with the hospital combined clinical
      and microbiology laboratory peritonitis database. RESULTS: Variables identified
      to be associated with an increased likelihood of peritonitis were: age (every 10
      years; OR, 1.26; 95% CI, 1.07-1.48), gender (female; OR, 1.91; 95% CI, 1.2-3.01),
      current smoker at entry to dialysis (OR, 1.71; 95% CI, 1.04-2.82) and the pre
      twin bag connection system (OR, 2.07; 95% CI, 1.22-3.52). CONCLUSION: Increasing
      age, female gender and smoking increased the risk of peritonitis. Identifying
      these risk factors will assist in the selection, training and monitoring of our
      PD population.

PMID- 17498119
TI  - Elevated resistin is related to inflammation and residual renal function in
      haemodialysed patients.
AB  - AIM: Resistin is an adipocytokine that recently generated much interest. Because
      of the fact that inflammation, endothelial cell damage or injury is invariably
      associated with such clinical conditions as thrombosis, atherosclerosis and their
      major clinical consequences, that is, cardiovascular disease and resistin play a
      role in linking inflammation and cardiovascular disease, the aim of the study was
      to assess resistin in correlation with markers of inflammation, endothelial cell
      injury and residual renal function in haemodialysed (HD) patients. METHODS: We
      assessed resistin, markers of coagulation: thrombin-antithrombin complexes (TAT),
      prothrombin fragments 1+2; fibrinolysis: tPA, plasminogen activator inhibitor
      type 1, plasmin-antiplasmin complexes (PAP); endothelial function/injury: von
      Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM);
      inflammation: high sensitivity C-reactive protein (hsCRP), tumour necrosis factor
      alpha and interleukin-6 (IL-6). RESULTS: Healthy volunteers and HD patients did
      not differ significantly regarding age, leucocyte count, serum iron, aspartate
      and alanine aminotransferases activities, calcium, cholesterol, tPA
      concentration. Triglycerides, CRP (assessed by high sensitivity method),
      phosphate, urea, creatinine, IL-6, tumour necrosis factor alpha, vWF, prothrombin
      fragments 1+2, TAT, PAP, thrombomodulin, ICAM, plasminogen activator inhibitor
      type 1 and resistin, were elevated in HD patients when compared with the control
      group. Serum albumin, total protein, haemoglobin and haematocrit were
      significantly lower in HD patients when compared with the control group. In HD
      patients with hsCRP 0e; 6 mg/L, resistin, IL-6, vWF and F1+2 were significantly
      higher, whereas tPA was significantly lower than in patients with hsCRP<6 mg/L.
      Moreover, HD patients with residual renal function have significantly lower
      resistin when compared with patients without it. Resistin was significantly
      higher in diabetics. In HD patients, resistin correlated significantly, in
      univariate analysis, with calcium, phosphate, PTH, TIBC, vWF residual renal
      function, urea, hsCRP, IL-6 and tended to correlate with tPA and ferritin. In the
      healthy volunteers, resistin was related to IL-6 and hsCRP. In multiple
      regression analysis, resistin was independently related to hsCRP, IL-6, residual
      renal function in HD patients. CONCLUSION: Elevated resistin related to markers
      of inflammation may represent a novel link between inflammation and
      adipocytokines in HD patients. Impaired renal function and inflammation are
      responsible for elevated resistin in HD patients.

PMID- 17498121
TI  - Rodent models of streptozotocin-induced diabetic nephropathy.
AB  - Streptozotocin-induced pancreatic injury is commonly used for creating rodent
      models of type 1 diabetes which develop renal injury with similarities to human
      diabetic nephropathy. This model can be established in genetically modified
      rodents for investigating the role of molecular mechanisms and genetic
      susceptibility in the development of diabetic nephropathy. In this report, the
      authors describe and compare the current protocols being used to establish models
      of diabetic nephropathy in rat and mouse strains using streptozotocin. The
      authors also list some of the histological criteria and biochemical measurements
      which are being used to validate these models. In addition, our review explains
      some of the key aspects involved in these models, including the impact of
      streptozotocin-dosage, uninephrectomy, hypertension and genetically modified
      strains, which can each affect the development of disease and the interpretation
      of findings.

PMID- 17498120
TI  - Renal response to an acute protein challenge in pregnant women with borderline
      hypertension.
AB  - BACKGROUND: The renal reserve (RR), assessed after an oral protein challenge or
      the intravenous administration of amino acids, is still present in healthy
      pregnant women (NP), although resting glomerular filtration rate (GFR) and renal
      plasma flow (RPF) increase progressively throughout normal gestation. No studies
      have addressed this issue in hypertensive gravidas; the aim of this trial was to
      evaluate renal response to an acute protein load (PL) in NP and pregnant women
      with borderline hypertension (HP). METHODS: Five NP, eight HP and eight healthy
      non-pregnant women (CG) were evaluated. After fasting overnight, all subjects
      received an oral water load (20 mL/kg of body weight), the urinary output was
      then replaced orally with equal volumes of water. After two 30 min periods, an 80
      g PL was provided. Creatinine clearance (CCr) was measured every 30 min from 1 h
      before and for 4 h following PL. Participants remained recumbent during the
      study, bladder emptiness was assessed by ultrasound immediately after each
      micturition. Baseline CCr was taken as the average of two 30 min periods before
      PL and peak Ccr as the maximal CCr recorded thereafter. RESULTS: The groups were
      similar with regard to age, weight or gestation age. Baseline CCr (NP: 118.5+/
      6.0, HP: 127.4+/-6.7 and CG: 99.8+/-2.9 mL/min, P=0.004 (CG vs NP and HP),
      increased after PL to NP: 223.5+/-9.8 to HP: 178.5+/-13 and to CG: 149.1+/-4.0
      mL/min, P<0.0004 (CG vs HP, CG vs NP and NP vs HP)). Peak minus baseline CCr was
      97.3+/-10.1; 46.3+/-12.7 and 48.3+/-4.8 for NP, HP and CG, respectively (P<0.006
      HP vs CG and NP). The peak CCr was obtained significantly earlier in both
      pregnant groups (Period 3) compared with the healthy non-pregnant women (Period
      5) (P=0.02). The fractional proximal reabsorption of sodium (FPRNa+) at peak CCr
      was similar in the groups (NP: 0.74+/-0.01 HP: 0.78+/-0.02 and CG: 0.74+/-0.03,
      P=not significant (NS)) as was the distal delivery of sodium (DDNa+) (NP: 5.8+/
      0.5; HP: 4.1+/-0.5 and CG: 4.3+/-0.4 meq/min, P=NS). Fractional excretion of urea
      (%) increased from 91.4+/-5.5 to 105.5+/-9.8%; 80.7+/-8.0 to 97.3+/-9.8; and
      44.4+/-7.8 to 86.0+/-7.1 in NP, HP and CG, respectively (P=NS). There was a trend
      towards a poorer maternal and fetal outcome in the HP group. CONCLUSION: Mid-term
      borderline HP failed to increase CCr as much as NP did after a protein challenge,
      suggesting altered functional response of the nephron or lessened sensitivity of
      renal vasculature to additional vasodilator stimuli. These results support the
      interest of additional prospective studies with a larger number of patients to
      confirm these findings and evaluate the value of RR tests as predictors of
      outcome of pregnancies at risk.

PMID- 17498122
TI  - The differential regulation of Smad7 in kidney tubule cells by connective tissue
      growth factor and transforming growth factor-beta1.
AB  - AIMS: Smad7 is an inhibitory Smad that regulates transforming growth factor-beta
      (TGF-beta) signaling. Connective tissue growth factor (CTGF) is recognized as a
      potent downstream mediator of the fibrogenic effects of TGF-beta1. SMAD binding
      sites have been identified in both TGF-beta and CTGF promoters. The effect of
      CTGF on Smad7 expression and its role in the regulation of Smad7 induced by TGF
      beta1 in renal tubular cells is unknown. METHODS: Human model of proximal tubular
      cells (HK-2 cells) was used and confirmed using a diabetic rat model. RT-PCR was
      performed to measure Smad7, TGF-beta1 and Smad2 and ELISA was performed to
      measure active TGF-beta1. CTGF or TGF-beta1 was silenced in HK-2 cells using
      siRNA methodology. RESULTS: TGF-beta1 induced Smad7 in a time-dependent manner,
      peaking at 30 min (P<0.0005) but sustained up to 24 hrs (p<0.005). Conversely,
      CTGF reduced Smad7, which was maximal at 24 hrs (p<0.05). This was supported by
      our in vivo data demonstrating that CTGF protein significantly increased while
      Smad7 mRNA level was reduced in a diabetic rat model. The basal expression level
      of Smad7 decreased in TGF-beta1 silenced cells compared to cells transfected with
      non-specific siRNA (p<0.0005). The basal expression level of Smad7 increased in
      CTGF silenced cells (p<0.05), which was increased by TGF-beta1 (p<0.005). Both
      mRNA and protein levels of TGF-beta1 decreased in CTGF silenced cells (p<0.05 and
      p<0.005 respectively) accompanied by reduction in Smad2 mRNA level in CTGF
      silenced cells. CONCLUSIONS: Smad7 is induced rapidly by TGF-beta1 limiting the
      response to TGF-beta1. CTGF likely plays a key role in promoting TGF-beta1
      activity by decreasing the availability of Smad7 and increasing Smad2.

PMID- 17498123
TI  - The pathogenic role of IgA1 O-linked glycosylation in the pathogenesis of IgA
      nephropathy.
AB  - Numerous abnormalities of the IgA immune system have been reported in IgAN but
      the most consistent finding remains aberrant IgA1 O-linked glycosylation of the
      IgA1 hinge region. The defect comprises reduced galactosylation of O-linked N
      acetylgalactosamine residues with or without changes in the terminal sialylation
      of the O-linked sugars. Aberrant O-galactosylation has been found in serum IgA1,
      in IgA1 isolated from tonsillar lymphocytes, and in IgA1 eluted from mesangial
      deposits. There is evidence that changes in IgA1 O-galactosylation lead to IgA
      immune complex formation and mesangial IgA deposition. Mesangial cells exposed to
      these IgA immune complexes proliferate and adopt a pro-inflammatory phenotype;
      they secrete cytokines, chemokines, growth factors and extracellular matrix
      components promoting glomerular inflammation and glomerulosclerosis. Recent
      evidence suggests that the control of IgA1 O-glycosylation is linked to class
      switching from IgD to IgA1 synthesis and that the pattern of IgA1 O-glycosylation
      may be programmed at the time of initial antigen encounter. IgA1 glycosylation
      varies between systemic and mucosal sites and the association of aberrant IgA1
      galactosylation with low affinity, polymeric IgA1 antibodies against mucosal
      antigens suggests undergalactosylated IgA1 may in fact be a mucosal glycoform of
      IgA1. Although suited to the mucosal compartment, when these IgA1 glycoforms
      enter the systemic circulation in appreciable quantities they deposit in the
      mesangium and trigger glomerular inflammation. This review will discuss the
      evidence for the role of IgA1 O-glycosylation in the pathogenesis of IgAN and
      propose an explanation for the presence of aberrantly O-glycosylated IgA1 in the
      circulation of patients with IgAN.

PMID- 17498125
TI  - Association of endothelial nitric oxide synthase gene intron 4 polymorphism with
      end-stage renal disease.
AB  - BACKGROUND: Nitric oxide (NO) released from endothelial cells is related to the
      maintenance of physiological vascular tone. The impairment of endothelial NO
      generation brought about by gene polymorphism is considered one of the
      deterioration factors in progressive renal disease. In the endothelial nitric
      oxide synthase (eNOS) intron 4 polymorphism, the presence of the aa genotype has
      been associated with cardiovascular and renal disease. The aim of this study was
      to investigate the presence of eNOS gene intron 4 polymorphism in patients with
      end-stage renal disease (ESRD). METHODS: A total of 114 patients and 94 controls
      were studied. DNA specimens were extracted from blood and amplified by polymerase
      chain reaction. The alleles were separated by agarose gel electrophoresis.
      Genotype distribution and allele frequencies were compared between groups using
      the chi-squared test. RESULTS: Statistical analysis revealed that the frequency
      of the eNOS4 genotype aa was significantly different in ESRD patients and in
      controls (P=0.016, OR=2.07, CI 95%: 1.14-3.74). There was also a statistically
      significant difference between ESRD patients and controls regarding allele
      carriers (P=0.004; OR=2.26; CI 95%: 1.29-3.96). When the frequencies of allele
      carriers in the diabetic nephropathy group and in the control group were
      compared, a significant difference was found (P=0.034, OR=2.28; CI 95%: 1.04
      5.00). CONCLUSION: This study showed a strong correlation between eNOS4a
      polymorphism and end-stage renal disease.

PMID- 17498124
TI  - Mycophenolate mofetil treatment for therapy-resistant glomerulopathies.
AB  - BACKGROUND: The management of steroid-resistant glomerulopathies remains a
      clinical problem. In this trial, we report a clinical observation of 43 patients
      treated with mycophenolate mofetil (MMF) for steroid-resistant glomerulopathies.
      METHODS: All patients underwent renal biopsies, and immunofluorescence and light
      microscopy examinations were conducted in all cases. All patients had been
      treated with prednisone at a dose of 1 mg/kg per day for at least 8 weeks. Of the
      43 patients, 16 were treated with cyclophosphamide and five were treated with
      cyclosporine A before MMF started. The primary study outcomes were the change in
      the urinary protein excretion, serum creatinine, comparing the levels at the
      start of MMF treatment with those at the end of the MMF treatment period. Changes
      in renal function were also estimated with Modification of Diet in Renal Failure
      calculation. Wilcoxon signed-ranks test was used as appropriate to compare data
      from the start with data at the end of the treatment period. RESULTS: The primary
      glomerular diseases represented included membranoproliferative glomerulonephritis
      in 23.2%, membranous glomerulonephritis in 18.6%, IgA nephropathy in 13.9%, focal
      segmental glomerulosclerosis in 9.3%, lupus nephritis (systemic lupus
      erythematosus) in 25.6% and pauci-immune glomerulopathy in 9.3% of patients. The
      mean follow-up time was 28.9+/-12 months. Before MMF treatment, 16 patients (37%)
      had nephrotic range proteinuria and 11 (26%) had renal insufficiency. The urinary
      protein before MMF treatment was 3.3+/-2.6 g/dL (0.6-9.6) and decreased
      significantly to 0.87+/-1.1 g/dL (0-5.5) at the end of the MMF treatment period
      (P=0.02). During treatment, complete remission was seen in 27 patients, partial
      remission in 10 patients and MMF failure in six patients. The serum creatinine
      level decreased significantly from 1.29+/-0.55 mg/dL (0.6-3.0) to 1.14+/-0.38
      mg/dL (0.5-2.4) post MMF therapy (P=0.046). Using the four-variable Modification
      of Diet in Renal Failure formula, the glomerular filtration rate increased from
      71.5+/-28 mL/min per 1.73 m2 to 78.1+/-27 mL/min per 1.73 m2 (P=0.021). Renal
      insufficiency resolved in seven of the 11 (63.6%) patients with renal
      insufficiency initially, two with membranoproliferative glomerulonephritis, two
      with membranous glomerulonephritis, one with focal segmental glomerulosclerosis,
      four with pauci-immune glomerulopathy, two with systemic lupus erythematosus
      nephritis, and in two patients de novo renal insufficiency developed. CONCLUSION:
      In general, MMF was well tolerated, and most of the patients achieved remission
      and improvement of renal functions. MMF treatment appeared to offer benefits to
      problematic patients refractory to conventional therapies for glomerulopathies.

PMID- 17498126
TI  - Benazepril slows progression of renal dysfunction in patients with non-diabetic
      renal disease.
AB  - AIM: The present study examined the effects of benazepril, an angiotensin
      converting enzyme inhibitor, on the progression of renal insufficiency in
      patients with non-diabetic renal disease. METHODS: Fifteen patients with non
      diabetic renal disease whose serum creatinine (Cr) ranged from 1.5 to 3.0 mg/dL
      were given either benazepril (2.5-5 mg) or placebo once daily for 1 year in a
      random crossover manner. In both periods, antihypertensive medications were
      increased if blood pressure was greater than 130/85 mmHg. Blood sampling and
      urinalysis were performed bimonthly throughout the study period. RESULTS: Blood
      pressure was similar when comparing the benazepril and the placebo periods (128+/
      12/83+/-6 vs 129+/-10/83+/-7 mmHg). Serum Cr significantly increased from 1.62+/
      0.18 to 1.72+/-0.30 mg/dL (P=0.036) during the placebo period, while there was no
      statistically significant increase in serum Cr during the benazepril period (from
      1.67+/-0.17 to 1.71+/-0.27 mg/dL). The slope of decrease of the reciprocal of
      serum Cr was steeper in the placebo period than in the benazepril period (
      0.073+/-0.067 vs-0.025+/-0.096/year, P=0.014). Urinary protein excretion was
      lower during the benazepril period than during the placebo period (0.57+/-0.60 vs
      1.00+/-0.85 g/gCr, P=0.006). Serum K was significantly higher in the benazepril
      period than in the placebo period (4.4+/-0.5 vs 4.2+/-0.5 mEq/L, P<0.001), but no
      patient discontinued benazepril therapy as a result of hyperkalemia. CONCLUSION:
      Long-term benazepril treatment decreased the progression of renal dysfunction in
      patients with non-diabetic renal disease by a mechanism that is independent of
      blood pressure reduction.

PMID- 17498127
TI  - Decision-making about suitability for kidney transplantation: Results of a
      national survey of Australian nephrologists.
AB  - AIM: This study aimed to elucidate the factors affecting nephrologists' decision
      making on patients' suitability for kidney transplantation. Given the reduced
      access to transplantation for Indigenous Australians, the role of patient's
      ethnicity was of particular interest. METHODS: A postal survey of practising
      nephrologists and trainees was undertaken in Australia. Each participant was
      provided with a unique set of 15 hypothetical patient descriptions, with
      demographic, clinical and behavioural factors randomly generated to ensure an
      overall balance of factors across the cases. The main outcome measure was whether
      kidney transplantation was recommended. RESULTS: Responding nephrologists and
      trainees were more likely to recommend transplantation for hypothetical patients
      who were young, of normal weight and described as compliant. They were less
      likely to recommend transplantation for smokers, or for people with diabetes or
      heart disease. No significant differences related to the patients' sex or
      ethnicity. The geographical location of the respondent was a significant
      determinant, with differences according to their State/Territory and their
      metropolitan/non-metropolitan location. CONCLUSION: When all other factors were
      held constant, nephrologists and trainees appear to base their decision-making
      regarding suitability for transplant on clinical and behavioural factors, rather
      than on the basis of ethnicity or sex. In practice, however, clinical and
      behavioural factors cluster with ethnicity, and this is likely to contribute to
      the current poor access to transplantation for Indigenous end-stage kidney
      disease patients. Apparent differences in decision-making according to the
      respondent's location may reflect variations in practice across the country.

PMID- 17498128
TI  - Dengue has a benign presentation in renal transplant patients: a case series.
AB  - AIM: Dengue fever and its complications are a poorly described entity in the
      renal transplant population. Previous reports in renal transplant patients
      suggest a high mortality rate. METHODS: We undertook a retrospective study of six
      cases of dengue fever in renal transplant patients during a dengue outbreak in
      Singapore in 2005 which involved a total of 1400 cases in the city state.
      RESULTS: Mean thrombocytopenia was 130,000/microL on presentation and
      80,000/microL at deffervescence. No dengue haemorrhagic fever, dengue shock
      syndrome, deaths or abnormal graft function were observed. Mean hospital stay was
      8.6 days. Four of six patients also had simultaneous CMV reactivation.
      CONCLUSION: In common with the majority of adults, dengue fever follows a benign
      course in the renal transplant population and dengue haemorrhagic fever is rare.
      This may be related to the relative immunosuppression reducing the risk for
      antibody-enhanced complications.

PMID- 17498129
TI  - Northern Australian kidney transplant unit: a viable option?
AB  - AIMS: Kidney transplant units in Australia are confined to large hospitals in
      major metropolitan areas, yet this may limit access and diminish outcomes in
      people who do not live in these large centres. The authors examined the viability
      of a kidney transplant unit located in northern Australia (NA), with particular
      emphasis on recipient outcomes and the number of donors. METHODS: 'Northern
      Australia' was arbitrarily defined as 'north of the tropic of Capricorn' for
      Queensland and Western Australia and included the entire Northern Territory. Data
      on donors and transplant recipients were provided by ANZDATA and ANZOD
      registries, identified by postcode. RESULTS: Between 1998 and 2004 in NA there
      were 163 deceased donor kidneys and 97.5% of available organs were transplanted.
      There were no Aboriginal/Torres Strait Islander (ATSI) donors from NA. Recipients
      from NA in this time included 55 patients receiving living grafts and 156
      receiving deceased donor grafts, of whom 36% were ATSI, making up half of the
      total ATSI transplanted in Australia during this time period. Compared with the
      rest of Australia, NA recipients were older, waited longer on dialysis, had
      longer ischaemic times and a greater number of human leucocyte antigen
      mismatches, and were more likely to be diabetic and obese. Despite the longer
      cold ischaemic time in NA recipients, no difference in immediate graft function
      was seen. ATSI recipients in NA, when compared with their southern Australian
      counterparts, had poorer patient survival (HR=3.19, 95% CI 1.44-7.08, P<0.001),
      but equivalent graft survival (HR=1.67, 95% CI 0.95-2.95, P=not significant) on
      multivariate analysis. Key factors that would influence feasibility of a Northern
      Australian transplant unit include adequate staffing, and support services in
      addition to currently available resources. CONCLUSION: Current donor numbers in
      NA are adequate for past recipients of kidney transplant, but may not cover
      future needs without a significant increase in donor rate. A transplant unit
      situated in northern Australian would require significant resources to ensure
      long-term viability and its effect on outcomes is uncertain.

PMID- 17498130
TI  - Primary renal lymphoma.

PMID- 17498132
TI  - A timely reminder about an evolving clinical entity: nephrogenic systemic
      fibrosis and gadolinium use in CKD.

PMID- 17498133
TI  - Species abundance distributions over time.
AB  - It has been known for 50 years that the time period over which data are collected
      affects the shape of empirical species abundance distributions. However, despite
      a recent resurgence of interest in characterizing and explaining these patterns
      the temporal component of species abundance distributions has been largely
      ignored. I argue that it is essential to take account of time, and not only
      because sampling duration can have a profound influence on the perceived shape of
      the distribution. Partitions of species abundance distributions based on temporal
      occurrence in the record will facilitate tests of both biological and neutral
      models and may lead to a better understanding of rarity. These temporal
      partitions also have interesting, but as yet barely explored, parallels with
      spatial ones such as the core-satellite division. Moreover, changes in abundance
      distributions across all three of Preston's temporal scales (sampling time,
      ecological time and evolutionary time) present rich opportunities for ecological
      research.

PMID- 17498134
TI  - Growth-mortality tradeoffs and 'personality traits' in animals.
AB  - Consistent individual differences in boldness, reactivity, aggressiveness, and
      other 'personality traits' in animals are stable within individuals but vary
      across individuals, for reasons which are currently obscure. Here, I suggest that
      consistent individual differences in growth rates encourage consistent individual
      differences in behavior patterns that contribute to growth-mortality tradeoffs.
      This hypothesis predicts that behavior patterns that increase both growth and
      mortality rates (e.g. foraging under predation risk, aggressive defense of
      feeding territories) will be positively correlated with one another across
      individuals, that selection for high growth rates will increase mean levels of
      potentially risky behavior across populations, and that within populations,
      faster-growing individuals will take more risks in foraging contexts than slower
      growing individuals. Tentative empirical support for these predictions suggests
      that a growth-mortality perspective may help explain some of the consistent
      individual differences in behavioral traits that have been reported in fish,
      amphibians, reptiles, and other animals with indeterminate growth.

PMID- 17498135
TI  - Biased data reduce efficiency and effectiveness of conservation reserve networks.
AB  - Complementarity-based reserve selection algorithms efficiently prioritize sites
      for biodiversity conservation, but they are data-intensive and most regions lack
      accurate distribution maps for the majority of species. We explored implications
      of basing conservation planning decisions on incomplete and biased data using
      occurrence records of the plant family Proteaceae in South Africa. Treating this
      high-quality database as 'complete', we introduced three realistic sampling
      biases characteristic of biodiversity databases: a detectability sampling bias
      and two forms of roads sampling bias. We then compared reserve networks
      constructed using complete, biased, and randomly sampled data. All forms of
      biased sampling performed worse than both the complete data set and equal-effort
      random sampling. Biased sampling failed to detect a median of 1-5% of species,
      and resulted in reserve networks that were 9-17% larger than those designed with
      complete data. Spatial congruence and the correlation of irreplaceability scores
      between reserve networks selected with biased and complete data were low. Thus,
      reserve networks based on biased data require more area to protect fewer species
      and identify different locations than those selected with randomly sampled or
      complete data.

PMID- 17498136
TI  - Ecological context influences pollinator deterrence by alkaloids in floral
      nectar.
AB  - Secondary compounds may benefit plants by deterring herbivores, but the presence
      of these defensive chemicals in floral nectar may also deter beneficial
      pollinators. This trade-off between sexual reproduction and defense has received
      minimal study. We determined whether the pollinator-deterring effects of a nectar
      alkaloid found in the perennial vine Gelsemium sempervirens depend on ecological
      context (i.e. the availability of alternative nectar sources) by monitoring the
      behavioural response of captive bumblebees (Bombus impatiens, an important
      pollinator of G. sempervirens in nature) to nectar alkaloids in several
      ecologically relevant scenarios. Although alkaloids in floral nectar tended to
      deter visitation by bumblebees, the magnitude of that effect depended greatly on
      the availability and nectar properties of alternative flowers. Ecological context
      should thus be considered when assessing ecological costs of plant defense in
      terms of pollination services. We consider adaptive strategies that would enable
      plants to minimize pollinator deterrence because of defensive compounds in
      flowers.

PMID- 17498137
TI  - Stress and domestication traits increase the relative fitness of crop-wild
      hybrids in sunflower.
AB  - After a decade of transgenic crop production, the dynamics of gene introgression
      into wild relatives remain unclear. Taking an ecological genetics approach to
      investigating fitness in crop-wild hybrid zones, we uncovered both conditions and
      characteristics that may promote introgression. We compared diverse crop-wild
      hybrid genotypes relative to wild Helianthus annuus under one benign and three
      stressful agricultural environments. Whereas relative fitness of crop-wild
      hybrids averaged 0.25 under benign conditions, with herbicide application or
      competition it reached 0.45 and was more variable. In some instances, hybrid
      fitness matched wild fitness (approximately 1). Thus, wild populations under
      agronomic stress may be more susceptible to introgression. Although
      'domestication' traits are typically considered unlikely to persist in wild
      populations, we found some (e.g. rapid growth and early flowering) that may
      enhance hybrid fitness, especially in stressful environments. Rigorous assessment
      of how particular genotypes, phenotypes, and environments affect introgression
      will improve risk assessment for transgenic crops.

PMID- 17498138
TI  - Evaluating plant-soil feedback together with competition in a serpentine
      grassland.
AB  - Plants can alter biotic and abiotic soil characteristics in ways that feedback to
      change the performance of that same plant species relative to co-occurring
      plants. Most evidence for this plant-soil feedback comes from greenhouse studies
      of potted plants, and consequently, little is known about the importance of
      feedback in relation to other biological processes known to structure plant
      communities, such as plant-plant competition. In a field experiment with three C4
      grasses, negative feedback was expressed through reduced survival and shoot
      biomass when seedlings were planted within existing clumps of conspecifics
      compared with clumps of heterospecifics. However, the combined effects of
      feedback and competition were species-specific. Only Andropogon gerardii
      exhibited feedback when competition with the clumps was allowed. For Sorghastrum
      nutans, strong interspecific competition eliminated the feedback expressed in the
      absence of competition, and Schizachyrium scoparium showed no feedback at all.
      That arbuscular mycorrhizal (AM) fungi may play a role in the feedback was
      indicated by higher AM root colonization with conspecific plant neighbours. We
      suggest that feedback and competition should not be viewed as entirely separate
      processes and that their importance in structuring plant communities cannot be
      judged in isolation from each other.

PMID- 17498139
TI  - Biomass-dependent susceptibility to drought in experimental grassland
      communities.
AB  - Earlier studies indicated that plant diversity influences community resistance in
      biomass when ecosystems are exposed to perturbations. This relationship remains
      controversial, however. Here we constructed grassland communities to test the
      relationships between species diversity and productivity under control and
      experimental drought conditions. Species richness was not correlated with biomass
      either under constant conditions or under drought conditions. However,
      communities with lower biomass production were more resistant to drought stress
      than those that were more productive. Our results also showed that ecosystem
      resistance to drought is a decreasing but nonlinear function of biomass. In
      contrast, species diversity had little and an equivocal effect on ecosystem
      resistance. From the results reported here, and the results of several previous
      studies, we suggest that high biomass systems exhibited a greater biomass
      reduction in response to drought than low biomass systems did, regardless of the
      relationship between plant diversity and community biomass production.

PMID- 17498140
TI  - Social information and emigration: lessons from immigrants.
AB  - 'Should I stay or should I go?' is a fundamental question facing any candidate
      for emigration, as emigrating without outside information has major costs. Most
      studies on this topic have concentrated on risk-reducing strategies (e.g.
      exploration) developed after leaving the natal habitat. The idea that information
      might be acquired before leaving has not been investigated. Immigrants carrying
      information about their origins could provide such information to potential
      emigrants in their initial habitat. We manipulated the density of common lizard
      (Lacerta vivipara) populations, to investigate whether immigrants originating
      from these populations transmitted such information to the population they
      joined. Emigration of the residents of this new population clearly depended on
      the origin of the immigrant. Immigrants are therefore a source of information, in
      this case about surrounding population densities, and may have a major effect on
      dispersal and species persistence in a fragmented habitat.

PMID- 17498141
TI  - A synthesis of experimental work on parasite local adaptation.
AB  - The study of parasite local adaptation, whereby parasites perform better on
      sympatric hosts than on allopatric hosts and/or better on their own host
      population than do other parasites, is of great importance to both basic and
      applied biology. Theoretical examination of host-parasite coevolution predicts
      that parasite migration rate, generation time and virulence all contribute to the
      pattern of parasite local adaptation, such that parasites with greater dispersal
      ability, more frequent reproduction and/or high virulence ought to exhibit
      increased infectivity on local hosts. Here, we present a meta-analysis of
      experimental work from 57 host-parasite systems across 54 local adaptation
      studies to directly test theoretical predictions concerning the effect of each
      attribute on parasite adaptation. As expected, we find that studies of parasites
      with higher migration rates than their hosts report local adaptation, as measured
      by infection success, significantly more often than studies of parasites with
      relatively low migration rates. Furthermore, this synthesis serves to identify
      biases in the current body of work and highlight areas with the greatest need for
      further study. We emphasize the importance of unifying the field with regard to
      experimental methods, local adaptation definitions and reported statistics for
      cross-infection studies.

PMID- 17498143
TI  - Scales of association: hierarchical linear models and the measurement of
      ecological systems.
AB  - A fundamental challenge to understanding patterns in ecological systems lies in
      employing methods that can analyse, test and draw inference from measured
      associations between variables across scales. Hierarchical linear models (HLM)
      use advanced estimation algorithms to measure regression relationships and
      variance-covariance parameters in hierarchically structured data. Although
      hierarchical models have occasionally been used in the analysis of ecological
      data, their full potential to describe scales of association, diagnose variance
      explained, and to partition uncertainty has not been employed. In this paper we
      argue that the use of the HLM framework can enable significantly improved
      inference about ecological processes across levels of organization. After briefly
      describing the principals behind HLM, we give two examples that demonstrate a
      protocol for building hierarchical models and answering questions about the
      relationships between variables at multiple scales. The first example employs
      maximum likelihood methods to construct a two-level linear model predicting
      herbivore damage to a perennial plant at the individual- and patch-scale; the
      second example uses Bayesian estimation techniques to develop a three-level
      logistic model of plant flowering probability across individual plants,
      microsites and populations. HLM model development and diagnostics illustrate the
      importance of incorporating scale when modelling associations in ecological
      systems and offer a sophisticated yet accessible method for studies of
      populations, communities and ecosystems. We suggest that a greater coupling of
      hierarchical study designs and hierarchical analysis will yield significant
      insights on how ecological processes operate across scales.

PMID- 17498144
TI  - Could the tree diversity pattern in Europe be generated by postglacial dispersal
      limitation?
AB  - The relative importance of contemporary climate and history as controls of
      geographical diversity patterns is intensely debated. A key example is the
      controversy over the extent to which temperate tree distributions and diversity
      patterns reflect postglacial dispersal limitation. Here, we focus on Central and
      Northern Europe, and show that recent estimates of tree migration rates < 100 m
      year(-1) imply that many species have probably not reached equilibrium with
      climate in this region. We then demonstrate that geographical accessibility from
      glacial refuges explains 78% of the geographical variation in the region's tree
      diversity and is a much stronger diversity predictor than climate. Finally, we
      show that realistic estimates of migration rates can be derived from the observed
      tree diversity pattern by assuming it to be purely dispersal driven. In
      conclusion, the tree diversity pattern in Central and Northern Europe could, to a
      large extent, be a result of postglacial dispersal limitation.

PMID- 17498145
TI  - Decelerating growth in tropical forest trees.
AB  - The impacts of global change on tropical forests remain poorly understood. We
      examined changes in tree growth rates over the past two decades for all species
      occurring in large (50-ha) forest dynamics plots in Panama and Malaysia. Stem
      growth rates declined significantly at both forests regardless of initial size or
      organizational level (species, community or stand). Decreasing growth rates were
      widespread, occurring in 24-71% of species at Barro Colorado Island, Panama (BCI)
      and in 58-95% of species at Pasoh, Malaysia (depending on the sizes of stems
      included). Changes in growth were not consistently associated with initial growth
      rate, adult stature, or wood density. Changes in growth were significantly
      associated with regional climate changes: at both sites growth was negatively
      correlated with annual mean daily minimum temperatures, and at BCI growth was
      positively correlated with annual precipitation and number of rainfree days (a
      measure of relative insolation). While the underlying cause(s) of decelerating
      growth is still unresolved, these patterns strongly contradict the hypothesized
      pantropical increase in tree growth rates caused by carbon fertilization.
      Decelerating tree growth will have important economic and environmental
      implications.

PMID- 17498146
TI  - A strong species-area relationship for eukaryotic soil microbes: island size
      matters for ectomycorrhizal fungi.
AB  - While the effects of habitat size and isolation have been successfully studied
      for macro-organisms, there is currently debate about their relative importance in
      explaining patterns of microbial species richness. In this study, we examine the
      species richness of a dominant group of eukaryotic soil microbes, ectomycorrhizal
      fungi, on 'tree islands' of constant age and host composition that range in size
      from < 10 to > 10,000 m(2). Our results show that ectomycorrhizal species
      richness is significantly reduced on smaller and more isolated tree islands, and
      the species-area slope that we observe (0.20-0.23) is similar to average slopes
      reported for macro-organisms. Additionally, species' occurrence patterns across
      tree islands and investment trends in fungal fruit bodies suggest that a trade
      off between competition and dispersal could play an important role in structuring
      ectomycorrhizal assemblages.

PMID- 17498147
TI  - Insularity and the determinants of lizard population density.
AB  - The relative effects of resource availability and partitioning on animal
      population density are unresolved yet central to ecology and conservation.
      Species-depauperate islands offer an intriguing test case. Across 643 lizard
      populations from around the world, local abundances are one order of magnitude
      higher on islands than on mainlands, even when controlled for resource
      availability. On mainlands, predator and competitor richness only weakly
      correlate with lizard densities. On islands, sharp reductions in predator and
      competitor richness are the dominant drivers of lizard abundance. Our results
      demonstrate the dramatic effect insularity has on the interplay between biotic
      and abiotic control of animal abundances and the heightened sensitivity of island
      communities to species' losses and gains.

PMID- 17498148
TI  - Within-plant signalling via volatiles overcomes vascular constraints on systemic
      signalling and primes responses against herbivores.
AB  - Plant volatiles play important roles in signalling between plants and insects,
      but their role in communication among plants remains controversial. Previous
      research on plant-plant communication has focused on interactions between
      neighbouring plants, largely overlooking the possibility that volatiles function
      as signals within plants. Here, we show that volatiles released by herbivore
      wounded leaves of hybrid poplar (Populus deltoides x nigra) prime defences in
      adjacent leaves with little or no vascular connection to the wounded leaves.
      Undamaged leaves exposed to volatiles from wounded leaves on the same stem had
      elevated defensive responses to feeding by gypsy moth larvae (Lymantria dispar
      L.) compared with leaves that did not receive volatiles. Volatile signals may
      facilitate systemic responses to localized herbivory even when the transmission
      of internal signals is constrained by vascular connectivity. Self-signalling via
      volatiles is consistent with the short distances over which plant response to
      airborne cues has been observed to occur and has apparent benefits for emitting
      plants, suggesting that within-plant signalling may have equal or greater
      ecological significance than signalling between plants.

PMID- 17498149
TI  - Resistance management in a native plant: nicotine prevents herbivores from
      compensating for plant protease inhibitors.
AB  - Plants deploy chemical defenses in complex mixtures, which are thought to be
      adaptive, but experimental tests have used artificial diets rather than plants.
      Herbivore attack on Nicotiana attenuata rapidly increases the production and
      accumulation of trypsin proteinase inhibitors (TPI) and the toxic alkaloid
      nicotine. By transgenically silencing their respective biosynthetic genes, we
      were able to abolish TPI activity and reduce inducible nicotine by 85%. Nicotine
      production was not affected by silencing pi or vice versa, and transformation did
      not alter levels of other metabolites examined. Spodoptera exigua, a native
      generalist herbivore that can compensate for heterologous TPI expression,
      performed better on TPI- or nicotine-deficient plants compared with the wild
      type. Because of a compensatory feeding response to TPI when nicotine is absent,
      larvae performed better on nicotine-deficient plants than they did on plants
      silenced in both defenses. The antifeedant toxin, nicotine, prevents this
      compensatory response. We conclude that N. attenuata counters an insect
      adaptation with a defensive synergism.

PMID- 17498150
TI  - Four decades of opposing natural and human-induced artificial selection acting on
      Windermere pike (Esox lucius).
AB  - The ability of natural selection to drive local adaptation has been appreciated
      ever since Darwin. Whether human impacts can impede the adaptive process has
      received less attention. We tested this hypothesis by quantifying natural
      selection and harvest selection acting on a freshwater fish (pike) over four
      decades. Across the time series, directional natural selection tended to favour
      large individuals whereas the fishery targeted large individuals. Moreover, non
      linear natural selection tended to favour intermediate sized fish whereas the
      fishery targeted intermediate sized fish because the smallest and largest
      individuals were often not captured. Thus, our results unequivocally demonstrate
      that natural selection and fishery selection often acted in opposite directions
      within this natural system. Moreover, the two selective factors combined to
      produce reduced fitness overall and stronger stabilizing selection relative to
      natural selection acting alone. The long-term ramifications of such human-induced
      modifications to adaptive landscapes are currently unknown and certainly warrant
      further investigation.

PMID- 17498151
TI  - The functional role of biodiversity in ecosystems: incorporating trophic
      complexity.
AB  - Understanding how biodiversity affects functioning of ecosystems requires
      integrating diversity within trophic levels (horizontal diversity) and across
      trophic levels (vertical diversity, including food chain length and omnivory). We
      review theoretical and experimental progress toward this goal. Generally,
      experiments show that biomass and resource use increase similarly with horizontal
      diversity of either producers or consumers. Among prey, higher diversity often
      increases resistance to predation, due to increased probability of including
      inedible species and reduced efficiency of specialist predators confronted with
      diverse prey. Among predators, changing diversity can cascade to affect plant
      biomass, but the strength and sign of this effect depend on the degree of
      omnivory and prey behaviour. Horizontal and vertical diversity also interact:
      adding a trophic level can qualitatively change diversity effects at adjacent
      levels. Multitrophic interactions produce a richer variety of diversity
      functioning relationships than the monotonic changes predicted for single trophic
      levels. This complexity depends on the degree of consumer dietary generalism,
      trade-offs between competitive ability and resistance to predation, intraguild
      predation and openness to migration. Although complementarity and selection
      effects occur in both animals and plants, few studies have conclusively
      documented the mechanisms mediating diversity effects. Understanding how
      biodiversity affects functioning of complex ecosystems will benefit from
      integrating theory and experiments with simulations and network-based approaches.

PMID- 17498152
TI  - Psychiatric treatment guidelines: doctors' non-compliance or insufficient
      evidence?

PMID- 17498153
TI  - Effects of implementation of psychiatric guidelines on provider performance and
      patient outcome: systematic review.
AB  - OBJECTIVE: To identify evidence from comparative studies on the effects of
      psychiatric guideline implementation on provider performance and patient outcome.
      Effects of different implementation strategies were reviewed. METHOD: Articles
      published between 1966 and March 2006 were searched through electronic databases
      and hand search. A systematic review of comparative studies of structured
      implementation of specific psychiatric guidelines was performed. Rates of
      guideline adherence, provider performance data, illness detection and diagnostic
      accuracy rates were extracted in addition to patient relevant outcome data.
      RESULTS: Eighteen studies (nine randomized-controlled trials, six non-randomized
      controlled studies and three quasiexperimental before-and-after studies) were
      identified. Effects on provider performance or patient outcome were moderate and
      temporary in most cases. Studies with positive outcomes used complex multifaceted
      interventions or specific psychological methods to implement guidelines.
      CONCLUSION: There is insufficient high-quality evidence to draw firm conclusions
      on the effects of implementation of specific psychiatric guidelines.

PMID- 17498154
TI  - Psychological treatments of subthreshold depression: a meta-analytic review.
AB  - OBJECTIVE: Subthreshold depression has a considerable impact on the quality of
      life and carries a high risk of developing major depressive disorder.
      Psychological treatments for subthreshold depression may be able to reduce
      depressive symptomatology and prevent the onset of major depression. METHOD: We
      conducted a meta-analysis of randomized controlled studies examining the effects
      of psychological treatments for subthreshold depression. We examined the effects
      on depressive symptoms and the preventive effects on the incidence of major
      depression. RESULTS: Seven high-quality studies with a total of 700 subjects were
      included. The mean effect size at post-test was 0.42 (95% CI: 0.23-0.60), with
      very low heterogeneity. The relative risk of developing a major depressive
      disorder in subjects who received the intervention was 0.70 (95% CI: 0.47-1.03; P
      = 0.07). CONCLUSION: Psychological treatments have significant effects on
      subthreshold depression. Furthermore, these interventions may prevent the onset
      of major depression.

PMID- 17498155
TI  - Personality traits in unaffected twins discordant for affective disorder.
AB  - OBJECTIVE: To examine whether a high genetic liability to develop affective
      disorder is associated with specific personality traits. METHOD: A cross
      sectional, high-risk, case-control study. Through nation-wide registers, healthy
      monozygotic (MZ) and dizygotic (DZ) twins with (high-risk twins) and without (the
      control group/low-risk twins) a co-twin history of affective disorder were
      identified. Personality traits were compared for a total of 211 high-risk and low
      risk twins. RESULTS: In univariate analyses, the high-risk twins had a higher
      level of neuroticism than the control twins (P = 0.03). In multivariate analyses,
      a high genetic liability to affective disorder was not significantly associated
      with neuroticism but correlated to sex, minor psychopathology and recent life
      events. CONCLUSION: A high genetic liability to affective disorder showed an
      association with neuroticism, but the association interacts with other predictors
      of affective disorder such as female gender, minor psychopathology and recent
      adversity.

PMID- 17498156
TI  - Evidence that moment-to-moment variation in positive emotions buffer genetic risk
      for depression: a momentary assessment twin study.
AB  - OBJECTIVE: The negative affective response to daily life stressors, which
      previous work suggest is a fundamental depression endophenotype, may be moderated
      by positive emotions. It was investigated whether positive affect (PA) buffers
      negative affect (NA) reactivity in response to stress and whether PA moderates
      the genetic predisposition to negative affect reactivity. METHOD: A total of 279
      twin pairs participated in a momentary assessment study with the experience
      sampling method, collecting appraisals of stress and affect in the flow of daily
      life. Lifetime diagnoses of depression were obtained. RESULTS: There was a
      significant interaction between stress appraisal of event (STRESS) and PA in the
      association with NA. The interaction between proband PA, proband STRESS and co
      twin lifetime depression showed that higher PA reduced the interaction between
      proband STRESS and co-twin lifetime depression. CONCLUSION: Positive emotions not
      only buffer against NA reactivity, but in addition attenuate genetic effects on
      negative mood bias in daily life.

PMID- 17498157
TI  - Low episodic memory performance as a premorbid marker of depression: evidence
      from a 3-year follow-up.
AB  - OBJECTIVE: To examine low episodic memory scores as a potential risk factor for
      depression. METHOD: A population-based sample of non-depressed individuals (20-64
      years) were re-examined 3 years after an initial screening (n = 708). At
      baseline, information on episodic memory scores, demographic and socioeconomic
      factors, alcohol use and anxiety diagnoses was collected. The data for depression
      diagnoses were collected at both baseline and follow-up. RESULTS: Logistic
      regressions, conducted on three separate study groups that were defined according
      to three assessments of episodic memory (i.e. free + cued recall, free recall,
      cued recall) among individuals who scored in the 25 lowest or highest percentiles
      in the memory tests, revealed that low episodic memory performance defined as the
      sum of free and cued recalls of organizable words constitutes a risk of
      depression diagnosis 3 years later. CONCLUSION: Low episodic memory performance
      predated depressive diagnosis and might be considered as a premorbid marker of
      depression.

PMID- 17498158
TI  - Depressive disorders and anti-parkinson drug treatment: a case register study.
AB  - OBJECTIVE: To estimate the rate of treatment with anti-parkinson drugs (APD)
      among patients with depression. METHOD: In a nationwide case register linkage
      study, all persons with a main diagnosis of depression during 5 years were
      identified. A control group of persons with diagnoses of osteoarthritis was
      included. The subsequent risk of getting treatment with APD was estimated for the
      two groups. Statistical analyses involved Poisson's regression and competing risk
      models. RESULTS: A total of 14 991 persons were included. The rate of getting APD
      was 2.57 (95% CI: 1.46-4.52) times higher for persons with depression than for
      persons with osteoarthritis. Overall, the rate was highest for men. However,
      women with depression had a 3.89 (95% CI: 1.98-7.62) times higher rate of APD
      treatment as women with osteoarthritis while no significant difference was found
      among men. CONCLUSION: Provided that prescription of APD reflects the presence of
      Parkinson's disease, results support a positive statistical association between
      depressive disorders and Parkinson's disease.

PMID- 17498159
TI  - Diagnostic stability and evolution of bipolar disorder in clinical practice: a
      prospective cohort study.
AB  - OBJECTIVE: To evaluate the long-term stability of International Classification of
      Diseases-10th revision bipolar affective disorder (BD) in multiple settings.
      METHOD: A total of 34 368 patients received psychiatric care in the catchment
      area of a Spanish hospital (1992-2004). The analyzed sample included patients
      aged > or =18 years who were assessed on > or =10 occasions and received a
      diagnosis of BD at least once (n = 1153; 71,543 assessments). Prospective and
      retrospective consistencies and the proportion of subjects who received a BD
      diagnosis in > or =75% of assessments were calculated. Factors related to
      diagnostic shift were analyzed with traditional statistical methods and Markov's
      models. RESULTS: Thirty per cent of patients received a BD diagnosis in the first
      assessment and 38% in the last assessment. Prospective and retrospective
      consistencies were 49% and 38%. Twenty-three per cent of patients received a BD
      diagnosis during > or =75% of the assessments. CONCLUSION: There was a high
      prevalence of misdiagnosis and diagnostic shift from other psychiatric disorders
      to BD. Temporal consistency was lower than in other studies.

PMID- 17498160
TI  - Association between antenatal depression and low birthweight in a developing
      country.
AB  - OBJECTIVE: There is a high prevalence of depression in south Asian women. We
      aimed to examine the association between antenatal depression and low birthweight
      (LBW) in infants in a rural community in Rawalpindi, Pakistan. METHOD: A total of
      143 physically healthy mothers with ICD-10 depression in the third trimester of
      pregnancy and 147 non-depressed mothers of similar gestation were followed from
      birth. Infant weight was measured and information collected on socioeconomic
      status, maternal body-mass index and sociodemographic factors. RESULTS: Infants
      of depressed mothers had lower birthweight (mean 2910 g) than infants of non
      depressed mothers (mean 3022 g). The relative risk for LBW (< or =2500 g) in
      infants of depressed mothers was 1.9 (95% CI 1.3-2.9). The association remained
      significant after adjustment for confounders by multivariate analyses.
      CONCLUSION: Low birthweight is a major public health problem in developing
      countries. Maternal depression during pregnancy predicts LBW. Interventions aimed
      at maternal depression may help improve infant outcomes.

PMID- 17498161
TI  - Reliability of personality disorder diagnosis during depression: the contribution
      of collateral informant reports.
AB  - OBJECTIVE: Research has found low concordance of personality disorder diagnoses
      made during depression versus after remission and made using patient versus
      collateral informants, but little is known about the reliability of personality
      disorder (PD) diagnoses made during depression using patient and collateral
      reports. METHOD: A total of 168 patients were evaluated for PDs during depression
      and following response using patient and close informant reports. kappa
      coefficients of inter-informant and test-retest reliability were calculated.
      RESULTS: After depression response, the proportion diagnosed with cluster A and C
      PDs fell by both patient and close informant report, and overall inter-informant
      reliability declined. Overall test-retest reliability did not differ between
      patients and informants. CONCLUSION: Collateral informants do not improve the
      reliability of PD diagnoses made during depressive episodes.

PMID- 17498163
TI  - Brain imaging in psychiatry--a study of 435 psychiatric in-patients at a
      university clinic.

PMID- 17498164
TI  - Exclusive, idiosyncratic and collective expertise in the interprofessional arena:
      the case of optometry and eye care in The Netherlands.
AB  - This paper addresses expertise as the foundation of professional boundaries and
      domains through a comparative study of four eye care occupations in the
      Netherlands. Claims of expertise are explored with an analysis of whether
      practitioners believe that expertise is exclusive to their profession. Results
      show that (a) established professions display a stronger sense of the
      'exclusiveness' of expertise; (b) idiosyncratic expertise is more common among
      encroaching professions than among established ones. These findings substantiate
      trends towards professionalism, as jurisdictional disputes on professional
      domains and boundaries usually occur between more established medical professions
      seeking to protect their knowledge area, and encroaching ones trying to expand
      theirs. The study next addresses the ways in which claims to expertise influence
      practitioners' attitudes towards professional status and professional practice.
      Attitudes to expertise are influenced by age, and affect professional work in the
      workplace. Practitioners who considered expertise as a collective characteristic
      were younger, undertook more examinations, more diagnoses, gave more treatments,
      referred less, and perceived more problems regarding inter-professional
      recognition of their professional status.

PMID- 17498165
TI  - Judging without criteria? Sickness certification in Dutch disability schemes.
AB  - The gate-keeping function that physicians perform in determining clients'
      physical and mental incapacities is widely assumed to be the main reason for the
      rising numbers of disabled people. The sharp rise in the number of disabled has
      led many to claim that the disability benefits schemes are untenable. In order to
      regain public control and to make disabled eligibility procedures more
      transparent guidelines have been introduced in which medical evaluations are
      conceptualised as formal rational decisions. It is, however, questionable whether
      such measures are helpful in achieving their stated aims. This paper is based on
      ethnographic research on the ways physicians evaluate the eligibility of clients
      for disability benefits. It argues that assessing incapacity involves much more
      than formal rational decision-making. Doctors' reasoning is contextual and
      deliberative in character, and thus their assessment of a client's incapacity is
      less a technical matter than a normative one. Instead of generating transparency,
      guidelines based on formal rationality make the complex deliberations on which
      such judgments are based invisible, because they deny the normative dimension of
      medical expert decision-making. Therefore, different measures have to be
      developed that allow this normative dimension to be articulated, since insight
      into this normative dimension is a necessary pre-condition to be able to
      criticise disability judgments at all.

PMID- 17498167
TI  - Globalization and medicine in Trinidad.
AB  - In a qualitative study of urban Trinidadians who work in the medical industry,
      the concept of medical globalization was provisionally analysed. Two research
      questions were addressed: what is globalization, in the context of mainstream
      medicine, and how is this process manifested in everyday practices? Four
      fundamental principles of medical globalization emerged from in-depth interviews
      and analysis of observational materials: (1) the notion of history as an
      autonomous force with globalization as the latest stage, (2) the expansion of
      'Total Market' philosophy as a driving social force, (3) the fragmentation of
      society into atomistic, self-interested, and competitive individuals, and (4) the
      adoption of a 'centralised' set of ideals as the normative core necessary for
      social order. In this paper, findings from this investigation and their
      implications are discussed. In particular, medical globalization is linked with
      major themes in medical sociological theory including dualism and medicalization.

PMID- 17498166
TI  - Afghan refugees and their general practitioners in The Netherlands: to trust or
      not to trust?
AB  - In-depth interviews with Afghan refugees living in The Netherlands about their
      experience of healthcare, have led to a series of narratives. This article
      focuses on the relationship between the refugee-patients and their general
      practitioners (GPs) from the participants' point of view. It was possible to
      distinguish four different types of narrative, by analysing the individual
      interviews into critical episodes. Building trust was identified as the crucial
      issue. A number of possible explanations are given for the differences found.
      Links are made to participant expectations in respect of health and healthcare
      and to their personal and social resources. The GP has a key role in the Dutch
      healthcare system, but is a novel phenomenon for refugees arriving from
      Afghanistan. The development of a relationship of trust is sometimes compromised
      by negative personal experience and also by stories relating such experiences
      circulating in the Afghan community. The elements that constituted positive and
      negative episodes and led to the development or undermining of trust were
      identified in the narratives. Negative experience tended to be interpreted as a
      sign of prejudice on the part of the healthcare professional. The findings of
      this study are discussed in the wider context of research into patient priorities
      in general practice.

PMID- 17498168
TI  - Therapeutic pluralism? Evidence, power and legitimacy in UK cancer services.
AB  - The integration of complementary and alternative medicine (CAM) into cancer
      services is increasingly discussed as a potential part of UK health policy but as
      yet there has been little sociological research examining this process. This
      paper examines the results of a study on the provision of CAM to cancer patients
      in two distinct organisational contexts: the hospice and the hospital. It is
      based on interviews with medical specialists, nursing staff and CAM therapists.
      This paper focuses on how integration is managed in each organisation, examining
      professional boundary disputes and inter-professional dynamics. Discussion
      focuses on the rhetorical and practical strategies that are employed by a variety
      of differently positioned interviewees to negotiate the complexities of the
      interface of CAM and biomedicine. The results show significant differentiation in
      how differently positioned cancer clinicians view and utilise the biomedical
      hierarchy of evidence. We argue that the integration of CAM should not be
      conceptualised as a mere challenge to biomedicine, or, as resulting in a linear
      process of de-professionalization. Rather, it should be seen as producing a
      complex array of processes, including strategic adaptation on the part of medical
      specialists and NHS organisations.

PMID- 17498169
TI  - Health-related quality of life and the transformation of symptoms.
AB  - This paper traces the development of health-related Quality of Life instruments
      over the last half century. It identifies the emergence of key components of
      quality of life measurement in other health status questionnaires between about
      1950 and 1980 and their formalization in Quality of Life instruments in the mid
      1980s. The common developmental thread that linked these Quality of Life
      instruments and their precursors was the identification of 'distal symptoms' that
      represented the impact of illness beyond its immediate bodily manifestations. The
      measurement of distal symptoms through Quality of Life instruments also served to
      detach symptoms from their customary patho-physiological referent. Other
      contemporary examples of these free-floating symptoms reinforce the argument that
      the nature and meaning of symptoms has been transformed over recent decades.

PMID- 17498170
TI  - Body Mass Index, masculinities and moral worth: men's critical understandings of
      'appropriate' weight-for-height.
AB  - Based on the Body Mass Index (BMI, kg/m(2)), most men in nations such as the UK
      and USA are reportedly overweight or obese. This is authoritatively defined as a
      massive and growing problem. Drawing from embodied sociology, critical obesity
      literature and qualitative data generated during an Economic and Social Research
      Council funded project on masculinities and weight-related issues, this paper
      offers a critical realist contribution to the obesity debate. Rather than
      endorsing the institutionalised war on fat, and correcting so-called 'laymen' who
      dismiss medicalized weight-for-height recommendations, the following presents and
      honours men's justificatory accounts for levels of body mass that medicine labels
      too heavy (implicitly or explicitly too fat). Men's critical understandings,
      which are connected to their displays of moral worth, are considered under three
      headings: the compatibility of heaviness, healthiness and physical fitness;
      looking and feeling ill at a supposedly 'healthy' BMI; and resisting irrational
      standardisation. By empirically 'bringing in' men's meanings, sensibilities and
      culturally informed aesthetics, this paper casts a different light on medicalized
      measures that support potentially corrosive obesity epidemic psychology.

PMID- 17498171
TI  - 'When you have children, you're obliged to live': motherhood, chronic illness and
      biographical disruption.
AB  - Recent work on biographical disruption has emphasised the critical importance of
      timing and context to the understanding of the effects of illness on identity.
      This paper takes a different approach by examining the inter-relationship between
      illness and key sources of identity, in this instance HIV infection and
      motherhood. It is argued that, viewed in this light, biographical disruption
      remains a powerful analytic framework with which to explore the intense threat
      which may be posed to key identities by chronic, potentially fatal illnesses, and
      the fundamental re-working of such identities occasioned by such threats. With
      reference to the empirical study on which this paper draws, it is shown that the
      twelve respondents' emphasis on their need to survive and to protect their
      children, represented a fundamental re-formulation of their identities as mothers
      and, therefore, a type of biographical disruption while paradoxically also
      containing elements of biographical reinforcement. It is further argued that the
      incorporation of such key identities into the analysis problematizes work that
      suggests that biographical disruption is less relevant to those who have
      experienced difficult lives, while also highlighting the need to take greater
      account of gender and caring responsibilities in further work in this field.

PMID- 17498176
TI  - The pathogenic helminth parasites of eels.
AB  - Although 63 and 55 species of helminths have been reported from each species of
      Atlantic eel and from 29 to 19 for each species of Pacific eel only the
      monogeneans Pseudodactylogyrus bini and P. anguillae and the nematode
      Anguillicola crassus, originally specific to species of Pacific eels, can be
      considered serious pathogens. None of the three are normally pathogenic to their
      preferred natural eel host species in the wild. Pseudodactylogyrus spp. only
      cause serious local gill damage when present on a host in large numbers under
      optimal conditions that facilitate transmission. This is the case in eel
      aquaculture, where infections can be controlled by drugs. Anguillicola crassus is
      only pathogenic to Anguilla anguilla and A. rostrata when Atlantic eels are
      introduced to the far east or when the parasites have been introduced to Europe.
      Here the parasite life cycle differs in that A. crassus can infect a wide range
      of intermediate hosts, employ paratenic hosts and survive as larvae for months in
      the swimbladder wall. This makes it an excellent colonizer. Its major pathogenic
      effects on eels result from haemorrhaging in, and thickening of, the swimbladder
      wall. It reduces the oxygen concentration in the swimbladder, reducing its
      ability to function as a hydrostatic organ, and increases the stress response of
      eels. In shallow lakes at warm temperatures this can result in mass mortalities.
      It is also feared that the parasite affects the ability of eels to migrate to the
      Sargasso Sea and so contributes to the decline in eel populations. Control by
      drug treatment is possible in culture, but not in the wild.

PMID- 17498177
TI  - Gene structure of an antimicrobial peptide from mandarin fish, Siniperca chuatsi
      (Basilewsky), suggests that moronecidins and pleurocidins belong in one family:
      the piscidins.
AB  - The gene of piscidin, an antimicrobial peptide, has been cloned from the mandarin
      fish, Siniperca chuatsi. From the first transcription initiation site, the
      mandarin fish piscidin gene extends 1693 nucleotides to the end of the 3'
      untranslated region and contains four exons and three introns. A predicted 79
      residue prepropeptide consists of three domains: a signal peptide (22 aa), a
      mature peptide (22 aa) and a C-terminal prodomain (35 aa). The shortage of XQQ
      motif in the prodomain of mandarin fish piscidin and the similar gene structure
      between moronecidins (piscidins) and pleurocidins may indicate that they are
      derived from the same ancestor gene. We thus suggest that piscidin should be used
      as a terminology for these antimicrobial peptides in the future. The mandarin
      fish piscidin mRNA was abundant in intestine, spleen, pronephros and kidney
      analysed by real-time polymerase chain reaction. After stimulation with lipopoly
      saccharides (LPS), a marked increase in transcripts was observed in most tissues,
      indicating that piscidin is not only a constitutively expressed molecule, but
      also has an increased response to bacterial infection. The synthetic, amidated
      mandarin fish piscidin exhibited different antimicrobial activity against
      different fish bacterial pathogens, especially against species of Aeromonas,
      which may to certain extent reflect the pathogenicity of these bacteria.

PMID- 17498178
TI  - Molecular typing by pulsed-field gel electrophoresis of Flavobacterium
      psychrophilum isolates derived from Japanese fish.
AB  - Sixty-four isolates of Flavobacterium psychrophilum from ayu, Plecoglossus
      altivelis altivelis (Temminck & Schlegel), and other fish (n=16) in Japan and the
      type strain (NCIMB 1947(T)) were typed using pulsed-field gel electrophoresis
      (PFGE) with endonuclease BlnI and XhoI. These isolates were classified into 20
      clusters and 42 genotypes by PFGE analysis. The most predominant cluster of
      isolates from ayu was cluster XII (n=20), followed by clusters XVII, XVI, XX, XI,
      IX, X, XIII and XV; the remaining 17 isolates from other fish were divided into
      clusters I, II, III, IV, V, VI, VII, VIII, XIV, XVIII and XIX. The PFGE genotype
      of isolates from ayu clearly differed from those of other fish. The isolates from
      ayu in Gunma Prefecture belonged to clusters XII, XVI, XVII and XX, and the
      strains of three of these clusters (XII, XVII and XX) were isolated from ayu in
      15 of 19 prefectures. PFGE typing enabled more accurate classification of
      isolates into clusters than previously achieved by analysing the restriction
      fragment length polymorphism of PCR products. These results suggest that F.
      psychrophilum isolated from ayu and other fish are genetically different and
      strains with several PFGE types have spread within Japan.

PMID- 17498179
TI  - Differences in Lepeophtheirus salmonis abundance levels on Atlantic salmon farms
      in the Broughton Archipelago, British Columbia, Canada.
AB  - Sea lice data collected from Atlantic salmon farms in the Broughton Archipelago
      between 2003 and 2005 were examined for inter-regional differences in mobile
      Lepeophtheirus salmonis (Kroyer) abundance using the generalized linear model
      procedure. Factors such as age of the salmon populations, location of farms and
      time of year had a significant effect on the abundance of the mobile stages of L.
      salmonis whereas water temperature and salinity did not. Separate evaluation of
      SLICE treatment data found no significant difference in treatment frequency among
      the areas but did show that there were significantly lower numbers of farm
      treatments during the summer months when compared with other seasons. The role of
      environment and wild fish in influencing sea lice abundance on the farmed salmon
      is discussed. The findings suggest that effective management programmes for sea
      lice should not only be based on geographical location but should take into
      account other factors which could influence lice abundance levels.

PMID- 17498180
TI  - Evaluation of lethal and non-lethal sampling methods for the detection of white
      sturgeon iridovirus infection in white sturgeon, Acipenser transmontanus
      (Richardson).
AB  - Pectoral fin tissue of white sturgeon was investigated as a potential non-lethal
      sample source for the detection of white sturgeon iridovirus (WSIV) infection.
      Histopathology and polymerase chain reaction (PCR) results using fin tissue were
      compared with the standard lethal histopathology sampling method that utilizes
      head tissue. Tissues for each of the three sampling methods were collected weekly
      for 8 weeks from individual sturgeon undergoing an experimental cohabitation
      challenge with fish infected with the Abernathy isolate of WSIV. Non-lethal fin
      histopathological evaluation did not reveal infection during the first 3 weeks of
      sampling, while non-lethal PCR and the lethal method were variable. However, all
      three sampling methods were equally capable of identifying infection from 4 to 8
      weeks post-exposure. Of the survivors tested, all were negative by PCR and the
      lethal method, and only one fish was identified as being positive by non-lethal
      fin histopathology. In another experiment, all three sampling methods were
      applied to asymptomatic WSIV carriers in a case study conducted at the Kootenai
      Tribal Sturgeon Conservation Hatchery. Results showed that both lethal and non
      lethal fin histopathology were equally effective in detecting infection, but PCR
      was unable to identify this strain of WSIV. Depending on the virus isolate, these
      results suggest that non-lethal sampling of fin tissue (histopathology or PCR) is
      comparable with the lethal sampling method at identifying WSIV infection once
      infection is established, and under certain circumstances may provide an
      alternative to lethal sampling.

PMID- 17498182
TI  - Overcoming opioid blockade from depot naltrexone (Prodetoxon).
AB  - AIM: To describe a situation in which an opioid-dependent patient overcame
      naltrexone blockade. DESIGN, CASE REPORT, SETTING: Addiction treatment center in
      St Petersburg, Russia. PARTICIPANT: Patient with naltrexone implant.
      INTERVENTION: Detoxification. MEASUREMENTS: Clinical observations. CONCLUSIONS:
      It is possible, but very difficult, to overcome naltrexone blockade by using
      large doses of heroin.

PMID- 17498183
TI  - Age- and gender-related differences in blood amphetamine concentrations in
      apprehended drivers: lack of association with clinical evidence of impairment.
AB  - BACKGROUND: New legislation aimed at combating driving under the influence of
      drugs (DUID) in Sweden stipulated zero-concentrations in blood for scheduled
      substances. DUID suspects (n = 300), with amphetamine as the only psychoactive
      drug identified in blood, were investigated in relation to age and gender. In a
      smaller retrospective sample (n = 70) the relationship between clinical tests of
      impairment were compared with the concentration of amphetamine in blood.
      MEASUREMENTS: All forensic blood samples were subjected to a broad toxicological
      screening analysis by immunoassay methods [enzyme multiplied immunoassay
      technique/cloned enzyme donor immunoassay (EMIT/CEDIA)] and positive results were
      verified by gas chromatography-mass spectrometry (GC-MS). The limit of
      quantitation (LOQ) for determination of amphetamine in blood was 0.03 mg/l.
      People suspected of being under the influence of drugs were examined by a
      physician who asked various questions about state of health and use of drugs and
      also administered simple psychomotor and cognitive tests of impairment. After
      conducting these tests the physician concluded whether the suspects were not
      impaired, slightly, moderately or highly impaired by drugs other than alcohol.
      FINDINGS: Among 300 DUID suspects with amphetamine in blood there were 246 men
      (82%) and 54 women (18%). Mean age (+/- SD) of the men was 37.1 +/- 8.7 years
      compared with 35.5 +/- 7.1 years for the women (P > 0.05). The frequency
      distribution of blood amphetamine concentration was positively skewed with mean,
      median and highest values of 1.0 mg/l, 0.9 mg/l and 7.1 mg/l, respectively. The
      mean concentrations were slightly higher in the women 1.11 mg/l (median 1.0 mg/l)
      compared with 0.97 mg/l (median 0.8 mg/l) in the men (P > 0.05). There was a weak
      but statistically significant correlation between the person's age and the
      concentration of amphetamine in blood (r = 0.18, P < 0.05). The results of
      clinical tests of impairment showed no relationship with the concentration of
      amphetamine in blood according to analysis of variance (P > 0.05). CONCLUSIONS:
      The lack of association between degree of drug influence and the concentration of
      amphetamine in blood speaks against the notion of introducing concentration per
      se limits or graded penalties depending on the blood-concentration of this
      stimulant. Zero-concentration limits or LOQ-limits are a much more pragmatic way
      to enforce DUID legislation.

PMID- 17498184
TI  - Measuring health-related quality of life in adolescence.
AB  - Until now, adolescents' health-related quality of life (HRQL) has primarily been
      examined together with children or adults. Specific aspects of adolescents' HRQL
      have often been neglected. However, this period in life has its own specific
      characteristics that must be considered in order to understand more about
      adolescents' HRQL. This review addresses the following issues: Which domains of
      HRQL are particularly important to adolescents? How are these important features
      of adolescent functioning related to overall HRQL? CONCLUSION: When examining
      adolescents' HRQL it is essential to acknowledge the specific aspects of
      adolescents' HRQL, rather than regard these individuals as either children or
      adults and to cover important topics that are especially salient during this
      period in life, such as: physical maturation and body image; peer relationships;
      intimacy and sexuality; and autonomy.

PMID- 17498185
TI  - Should new reference values on the AIMS test need to be established for Dutch
      children?

PMID- 17498186
TI  - Must infants with colic really be hospitalized?

PMID- 17498187
TI  - Physician consultation and antibiotic prescription in Swedish infants: population
      based comparison of group daycare and home care.
AB  - BACKGROUND: Daycare infants have more infectious episodes, see a physician more
      often, and are prescribed antibiotics more often than home care infants. AIM: To
      compare physician consultations and antibiotic prescription in daycare children
      and home care children taking number of symptom days, sociodemographic factors,
      concern about infectious illness and antibiotic knowledge into account. METHODS:
      For a cohort of Swedish 18-month-old children all infectious symptoms, physician
      consultation and antibiotic prescriptions were registered during 1 month.
      RESULTS: 561 infants with daycare outside the home and 278 with daycare at home
      were included. Of the daycare infants, 23.2% saw a physician and 11.4% were
      prescribed antibiotics, as compared with 10.8% physician consultations and 5.0%
      antibiotic prescription for the home care infants. For daycare infants the crude
      odds ratio for physician consultation were 2.49 (1.63-3.82) and for antibiotic
      prescription 2.43 (1.34-4.41) compared with home care infants. However, these
      differences were no longer statistically significant when background data,
      concern about infectious illness and reported symptoms were taken into account.
      CONCLUSION: When background data, concern about infectious illness and reported
      infectious symptoms were taken into account daycare infants saw a physician and
      was prescribed antibiotics in the same way as home care infants.

PMID- 17498188
TI  - A population based 10-year study of neonatal air transport in North Norway.
AB  - AIM: This study audits the activity of the neonatal air transport team in
      Norway's two northernmost counties. METHODS: Data on all air transports to or
      from the regional Neonatal Intensive Care (NICU) Unit within a 10-year period
      were collected. RESULTS: Two hundred and thirty-eight acute transports were
      conducted during the study period; 169 referrals to the NICU and 69 transfers to
      national surgical and cardiac centres. Only 13 very low birth weight infants were
      transported; the in utero transport rate was 95% for this patient population. The
      adjusted risk of death and/or intracranial haemorrhage for outborn very low birth
      weight infants was five-fold increased compared to those not transported
      postnatally. Babies with congenital heart disease comprised the one-fourth of all
      transports. The long-term mortality was 14% for the whole study population, and
      29% for infants with congenital heart disease. Only seven deaths (3.2%) were
      defined as being transport-related; death during or within 24 h after transport.
      However, preventable complications like temperature instability, hypoglycaemia
      and hypo-/hypercapnia occurred in 10-20% of all transports. CONCLUSION: The
      transport related mortality was low in this study, however very low birth weight
      infants and infants with major congenital heart disease showed a relatively poor
      outcome.

PMID- 17498189
TI  - Look-back study of Hepatitis C in teenagers after blood transfusions as neonates.
AB  - AIM: To conduct a single-centre "look-back" study of the prevalence of hepatitis
      C in teenagers who had received blood products as newborns, prior to hepatitis C
      virus (HCV) blood donor screening. METHODS: Using blood bank records, we
      identified 732 surviving teenagers aged 14-18 years who had received blood
      products as neonates during 1986-1990. Letters recommending HCV antibody testing
      were sent to 732 surviving teenagers; 581 recipients were contacted and invited
      to undergo testing, and, of these, 429 consented (59% of the survivors). HCV
      antibody testing was performed on all and HCV-RNA was tested on those who were
      antibody positive. RESULTS: Three teenagers (0.7%, 95% CI 0.54-0.86) tested
      positive for HCV antibodies and all three were HCV-RNA positive. There were no
      cases in which antibodies were detected and polymerase chain reaction (PCR) was
      negative. Two of the three had mildly elevated liver enzymes and all three had
      mild inflammatory activity and low fibrosis scores on liver biopsy. CONCLUSIONS:
      The look-back process, even in a single centre with a stable urban population, is
      relatively inefficient in screening at-risk populations. Although the prevalence
      of hepatitis C in this sample was relatively low, paediatricians should offer
      screening to teenagers and young adults who received blood products in the
      neonatal period.

PMID- 17498190
TI  - Nasal carriage of Staphylococcus aureus in 4-6 age groups in healthy children in
      Afyonkarahisar, Turkey.
AB  - AIM: Staphylococcus aureus is a common cause of disease, particularly for
      colonized persons. Although methicillin-resistant S. aureus (MRSA) infection has
      frequently reported, population-based S. aureus and MRSA colonisation estimates
      are lacking. Our objective in this report is to present the prevalance of S.
      aureus carriage among 4-6 age groups healthy children in our region. METHODS:
      Nasal samples for S. aureus culture were obtained from healthy children.
      Sociodemographic features and the data related with risk factors were obtained
      from the parents of the children. Nasal swabs were inoculated on to a variety of
      bacteriological culture media, which were then incubated at 35 +/- 1 degrees C
      for 16-18 h. Antimicrobial susceptibility testing of the isolates was determined
      according to Clinical and Laboratory Standard Institute (CLSI, 2005) guidelines.
      RESULTS: In this study 1134 children between 4 and 6 years old age were
      evaluated; 607 (53.5%) of the subjects were boys and 527 (46.5%) were girls. S.
      aureus was isolated in 322 (28.4%) subjects and MRSA was isolated in 3 (0.3%)
      subjects of them. All of the MRSA isolates were found in healthcare workers'
      children. CONCLUSIONS: This first assessment of this study is that nearly one
      third of the 4-6 age group healthy children population present nasal carriage of
      S. aureus in Turkey. However, it also shows that the rate of MRSA carriage
      remains low. In addition, it is considered that MRSA colonization may be a risk
      factor for healthcare workers' children.

PMID- 17498191
TI  - Increased laryngeal lavage lipid-laden macrophage index during acute
      bronchiolitis.
AB  - AIM: To investigate aspiration risks associated with bronchiolitis in infants
      using the lipid-laden macrophage index (LLMI) from laryngeal lavages. METHODS:
      Laryngeal lavages from 29 infants with acute bronchiolitis caused by respiratory
      syncytial virus were evaluated (acute stage). Repeated studies were then
      performed at 3-4 weeks after the initial study (remission stage). Lavage cell
      counts and differentials were determined. The amount of lipid per single
      macrophage was evaluated and the LLMI was determined by evaluating 100 cells. In
      addition, 24-h pH monitoring (pHm) was performed in 16 patients. RESULTS: The
      LLMIs in the acute stage were significantly higher than those in the remission
      stage (p < 0.05). The neutrophil percentage of the laryngeal lavage correlated
      significantly with the LLMI (r = 0.707, p < 0.0001) during the acute stage of
      bronchiolitis. When patients were divided into pHm-positive (n = 5) and pHm
      negative (n = 11) subgroups, a significant decrease in LLMI between acute and
      remission stages was noted among the pHm-positive (p < 0.01) subgroup, but not in
      the pHm-negative subgroup. CONCLUSION: These findings suggest that there is a
      transient increased LLMI in patients with bronchiolitis, which could be caused by
      gastroesophageal reflux.

PMID- 17498193
TI  - Gastro-oesophageal reflux disease: oesophageal impedance versus pH monitoring.
AB  - Gastro-oesophageal reflux occurs frequently during the first months of life.
      Infants receive frequent milk feeds, and because milk is a potent buffer of
      gastric acidity, oesophageal impedance should detect more reflux than pH
      recording. Indeed, impedance has the advantage over pH monitoring of being
      independent of pH, and as a consequence, of being better adapted to measure
      reflux during postprandial periods when reflux is buffered and to detect symptoms
      associated with non-acid or weakly acid reflux episodes. Numerous episodes are
      detected by one of these techniques (pH monitoring or impedance) in children.
      Most studies using the impedance technique consider very small numbers of
      patients, and there are few reports linking data from diagnostic impedance
      procedures to clinical outcome in symptomatic patients. Data suggesting that
      impedance does offer a clear-cut benefit in paediatric clinical practice are
      missing. The high cost of the material and the investment in time necessary for
      interpretation of the recording, remains a handicap. It is mandatory, despite
      ethical difficulties, to obtain normal ranges for intraluminal impedance
      monitoring. CONCLUSION: As pH monitoring is part of impedance technology, it is
      likely that the latter will replace pH monitoring despite the current lack of
      scientific evidence demonstrating a relation between symptoms, oesophageal damage
      or response to reflux treatment and impedance-pH results.

PMID- 17498194
TI  - The impact of pre- and post-natal smoke exposure on future asthma and bronchial
      hyper-responsiveness.
AB  - AIM: To analyse the impact of pre- and post-natal smoke exposure on asthma
      presence, bronchial hyper-responsiveness, airway function and active smoking in
      early adulthood. METHODS: We have prospectively studied 101 children hospitalized
      due to wheezing before the age of 2 years. The cohort was re-investigated at age
      17-20 years and tested for airway function and bronchial hyper-responsiveness.
      Data on maternal smoking during pregnancy were obtained from the Swedish Medical
      Birth Register. RESULTS: There was a significant, independent correlation between
      both pre- and post-natal smoke exposure and asthma at age 17-20 years, OR 3.5
      (1.1-11.3) and 3.4 (1.2-10.1), respectively. Maternal smoking during pregnancy
      was an independent risk factor for current bronchial hyper-responsiveness, OR 6.6
      (1.2-35.5). Pre-natal smoke exposure seemed to negatively affect small airway
      function in early adulthood due to structural changes. Post-natal smoke exposure
      was independently associated with an increased risk of current smoking, OR 7.4
      (1.6-35.2). CONCLUSION: In subjects hospitalized due to early wheezing, pre- and
      post-natal smoke exposure increase the risk of asthma in early adulthood. The
      connection between pre-natal smoke exposure and asthma appears to be mediated via
      the development of bronchial hyper-responsiveness. Smoke exposure in infancy is
      associated with an increased risk of active smoking in early adult age, which is
      in turn linked to current asthma.

PMID- 17498195
TI  - Seeing through the blind! Ability of hospital staff to differentiate morphine
      from placebo, in neonates at a placebo controlled trial.
AB  - AIM: To investigate whether professional training and/or clinical experience
      affect the ability of caregiver to assess clinical signs of pre-emptive morphine
      analgesia. METHODS: In the Neurological Outcomes & Pre-emptive Analgesia In
      Neonates trial preterm infants undergoing mechanical ventilation were randomized
      to receive continuous infusion, either of morphine or placebo blinded. Staff from
      centres in Sweden (Stockholm and Orebro) completed an assessment form. RESULTS: A
      total of 360 assessment forms were collected from 52 neonates. In 59% of the
      cases, caregivers correctly identified patients group. Comparable proportion of
      answers were correct between physicians, nurses and assistant nurses (63, 60 and
      54%, respectively, p = 0.60). Staff with Neonatal intensive care unit experience
      <1 year identified 63%, as compared to 65% for working 1-5 year, and 55% that has
      been working >5 years (p = 0.28). Staff's ability to correctly identify group
      assignment was reduced by amount of additional morphine (p < 0.01) and severity
      of illness (p = 0.01). CONCLUSIONS: Clinical medical staffs, including
      neonatologists, have great difficulties in assessing the presence and severity of
      pain. Further studies should focus on the methods for assessment of prolonged
      pain in preterm neonates, define the effects of adequate analgesia, and
      investigate the clinical factors that may alter neonatal responses to acute and
      prolonged pain.

PMID- 17498196
TI  - Effects of the dual endothelin receptor antagonist tezosentan and hypertonic
      saline/dextran on porcine endotoxin shock.
AB  - AIM: To evaluate the haemodynamic effects of the dual endothelin receptor
      antagonist tezosentan, both alone and combined with hypertonic saline/dextran
      (HSD), on porcine endotoxin shock, with focus on cardiopulmonary circulation. The
      effects on gas exchange and short-term survival were also studied. METHODS: A
      prospective, randomized experimental study was carried out. Thirty-two
      anaesthetized pigs underwent pulmonary and carotid artery catheterization.
      Following haemodynamic stabilization and baseline measurements, endotoxaemia was
      induced by an Escherichia coli-endotoxin infusion over 180 min and the animals
      observed another 120 min. After 60 min of endotoxaemia, directly before
      intervention, animals were randomized into four groups: a tezosentan group, an
      HSD group, a combined tezosentan/HSD group and a control group. The consequent
      haemodynamic effects and blood gas results were recorded. RESULTS: The endotoxin
      infusion reduced mean arterial blood pressure from 111 +/- 14 (mean +/- standard
      deviation) to 77 +/- 27 mmHg and cardiac index from 126.9 +/- 27.2 to 109.3 +/-
      22.6 mL min(-1) kg(-1) within 90 min in the control group. In addition, endotoxin
      simultaneously increased mean pulmonary artery pressure from 24 +/- 17 to 38 +/-
      19 mmHg and reduced arterial oxygenation from 18.9 +/- 2.0 to 12.2 +/- 5.3 kPa.
      Tezosentan, alone and combined with HSD, reversed the pulmonary hypertension and
      prevented the reduction in cardiac index and arterial oxygenation, resulting in
      reduced metabolic acidosis. Additionally, in the tezosentan group, the mean
      arterial blood pressure was reduced to the same level as in controls, an effect
      not prevented by the addition of HSD. It was found that all three interventions
      improved survival rates. CONCLUSION: Tezosentan, alone and in combination with
      HSD, improved cardiac index and arterial oxygenation. The addition of HSD to
      tezosentan treatment did not improve the endotoxin-induced hypotension, but
      beneficial effects on microcirculation and systemic oxygenation were seen despite
      low perfusion pressure, as indicated by increased SvO(2) and reduced metabolic
      acidosis.

PMID- 17498197
TI  - Rituximab for the treatment of autoimmune cytopenias in children with immune
      deficiency.
AB  - Autoimmune cytopenias are well recognised in patients with primary immune
      deficiency, but treatment may be difficult. We report eight children with
      autoimmune cytopenias (autoimmune haemolytic anaemia, autoimmune
      thrombocytopenia, autoimmune neutropenia) complicating immune deficiency states
      (common variable immunodeficiency, Wiskott-Aldrich Syndrome, autoimmune
      lymphoproliferative syndrome, combined immunodeficiency) treated with between 1
      and 3 courses of rituximab (anti-CD20). Responses occurred for 90% of treatments
      but relapse rates (after a median of 53 weeks) were high (78%). We conclude that
      rituximab is an effective treatment for autoimmune cytopenias in children with
      immune deficiencies, but repeated courses of treatment may be needed.

PMID- 17498198
TI  - Vascular fluorescence casting and imaging cryomicrotomy for computerized three
      dimensional renal arterial reconstruction.
AB  - Authors from the Netherlands studied the use of a casting technique,
      cryomicrotome imaging and three-dimensional computer analysis to visualise and
      reconstruct the arterial anatomy in a porcine kidney model. They found that this
      could be done satisfactorily to a resolution of 50 microm. OBJECTIVE: To assess
      the combined use of a casting technique, cryomicrotomy imaging, and three
      dimensional (3D) computer analysis as a method for visualizing and reconstructing
      the arterial vascular tree in a porcine renal model. MATERIAL AND METHODS: The
      arterial branches of two porcine kidneys were filled with a fluorescent cast,
      after which they were cut into slices of 50 microm in an imaging cryomicrotome.
      From each section, digital images of the cutting plane of the sample were taken
      and stored in the computer, after which stacks of images were rendered in 3D.
      RESULTS: A 3D computerized reconstruction of the arterial vascular tree was
      constructed and showed the complete arterial anatomy up to arterioles of 50
      microm. CONCLUSION: With visualization by fluorescence imaging cryomicrotomy, the
      anatomical and 3D reconstruction of the renal arterial blood supply in a pig
      kidney is possible up to a resolution of 50 microm.

PMID- 17498199
TI  - Body mass index and oxidative DNA damage: a longitudinal study.
AB  - Leanness has been shown to be related to an increased risk of some cancer forms,
      including lung cancer. However, biological evidence supporting a causal link
      between leanness and carcinogenesis is limited. The authors investigated
      longitudinally the association between body mass index (BMI) and levels of
      urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, using
      data from 174 healthy employees who participated in a lifestyle intervention
      study. 8-OHdG levels were measured using automated high-performance liquid
      chromatography and adjusted for urinary creatinine levels. Analysis of repeated
      measurements using a random effects model detected a statistically significant
      inverse association between BMI and 8-OHdG levels (P = 0.003); one unit decrease
      in BMI was associated with a 2.7% (95% confidence interval 0.9-4.4) increase in 8
      OHdG levels. The association was pronounced among men consuming less than 20
      cigarettes per day (8.8% increase per unit decrease in BMI) and among non-smoking
      men (3.7% increase). The results based on a longitudinal observation suggest that
      weight loss is associated with increased oxidative DNA damage, a state presumably
      related to an increased risk of cancer.

PMID- 17498200
TI  - Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with
      wild-type or mutant epidermal growth factor receptor.
AB  - Cetuximab (Erbitux, IMC-C225) is a monoclonal antibody targeted to the epidermal
      growth factor receptor (EGFR). To clarify the mode of antitumor action of
      cetuximab, we examined antibody-dependent cellular cytotoxicity (ADCC) activity
      against several tumor cell lines expressing wild-type or mutant EGFR. ADCC
      activity and complement-dependent cytolysis activity were analyzed using the
      CytoTox 96 assay. ADCC activities correlated with the EGFR expression value (R =
      0.924). ADCC activities were detected against all tumor cell lines, except K562
      cells in a manner dependent on the cellular EGFR expression level, whereas
      complement-dependent cytolysis activity was not detected in any of the cell
      lines. The ADCC activity mediated by cetuximab was examined in HEK293 cells
      transfected with wild-type EGFR (293W) and a deletional mutant of EGFR (293D) in
      comparison with the mock transfectant (293M). ADCC activity was detected in 293W
      and 293D cells, in a cetuximab dose-dependent manner, but not in 293M cells
      (<10%). These results indicate that ADCC-dependent antitumor activity results
      from the degree of affinity of cetuximab for the extracellular domain of EGFR,
      independent of EGFR mutation status. These results suggest ADCC activity to be
      one of the modes of therapeutic action of cetuximab and to depend on EGFR
      expression on the tumor cell surface.

PMID- 17498201
TI  - Inhibition of axonal outgrowth in the tumor environment: involvement of class 3
      semaphorins.
AB  - That tumors lack innervation is dogma in the field of pathology, but the
      molecular determinants of this phenomenon remain elusive. We studied the effects
      of conditioned media from Colon 26 and B16 mouse tumor cell lines on the axonal
      outgrowth and cellular differentiation of embryonic Institute of Cancer Research
      (ICR) mouse dorsal root ganglion cells. Tumor-conditioned media suppressed dorsal
      root ganglion axonal extension but had no effect on neuronal or glial
      differentiation. We found that the tumor cells expressed most of the class 3
      semaphorins - axon guidance molecules. Blocking the activity of class 3
      semaphorins with the soluble receptor neuropilin-1 significantly counteracted the
      tumor-induced inhibition of axonal extension. Together, these results suggest a
      role for tumor-secreted class 3 semaphorins in selectively inhibiting axonal
      outgrowth of dorsal root ganglion neurons.

PMID- 17498202
TI  - Oral delivery of tumor-targeting Salmonella for cancer therapy in murine tumor
      models.
AB  - Tumor-targeting bacteria have been investigated intensively in recent years as
      anticancer agents. To ensure the reliability of infection, bacteria have
      conventionally been injected intravenously or intraperitoneally into animals or
      humans. However, systemic infection of bacteria is rather inconvenient and
      carries the risk of obvious toxicity. Here we tested whether Salmonella
      typhimurium VNP20009, a tumor-targeting strain, could be administrated orally for
      tumor therapy. Tumor-targeting potential, antitumor effects, as well as toxicity
      of orally administrated VNP20009 were investigated in this study. Oral delivery
      of VNP20009 not only exhibited high tumor-targeting potential, but also led to a
      significant anticancer effect by delaying tumor growth and prolonging survival in
      murine tumor models. As part of combination therapy, orally administrated
      bacteria notably improved the antitumor effect of cyclophosphamide. In vitro and
      in vivo studies showed that VNP20009 significantly induced tumor cell apoptosis.
      No obvious toxicity was observed during the treatments with oral inoculation of
      VNP20009. Comparative analysis of toxicity in tumor-bearing and tumor-free mice
      further revealed that orally administrated Salmonella had high safety compared to
      conventional systemic infection of bacteria. The findings indicated that oral
      administration of tumor-targeting bacteria is effective and safe. This approach
      provides a novel avenue in the application of bacteria as a potential antitumor
      agent.

PMID- 17498203
TI  - Tissue factor (TF) and vascular endothelial growth factor (VEGF) expression in
      colorectal cancer: relation with cancer recurrence.

PMID- 17498204
TI  - Faecal incontinence in male patients.
AB  - OBJECTIVE: Data concerning faecal incontinence (FI) in men are lacking. The aim
      of this study was to evaluate the historical aetiology and contrast aetiologies
      in younger and older men suffering from FI. METHOD: After institutional review
      board approval, a retrospective chart review was undertaken of all patients with
      FI seen between 1999 and 2005. The data of male patients was further analysed to
      assess the impact of age and historical aetiology on FI. RESULTS: A total of 404
      males were included, 203 patients were <70 years of age (group A) and 201
      patients were >or=70 years of age (group B). The most common prior diagnosis in
      group A was perianal sepsis in 23 (11.3%) patients and symptomatic haemorrhoids
      in 20 (9.9%) patients; in group B it was prostate cancer in 57 (28.4%) patients,
      symptomatic haemorrhoids in 31 (15.4%) patients and neurological diseases in 18
      (9%) patients. The most common prior procedure in group A was restorative
      proctectomy/proctocolectomy in 32 (15.8%) patients, fistulotomy or
      haemorrhoidectomy in 21 (10.3%) and 19 (9.4%) patients respectively. In group B,
      radiation therapy for prostate cancer was utilized in 48 (23.9%) patients and
      haemorrhoidectomy in 29 (14.4%) patients. Comparing group A and group B relative
      to diagnosis - perianal sepsis, perineal trauma, congenital disorders, HIV
      infection and anal cancer were more common in group A, whereas prostate cancer,
      neurological diseases and colon cancer were significantly more common in group B.
      CONCLUSION: Prostate cancer, symptomatic haemorrhoids, perianal sepsis, rectal
      cancer and a history of restorative rectal resection were common associations
      with FI in men. The aetiologies for FI in men vary with age.

PMID- 17498205
TI  - Clarifying the TNM staging of rectal cancer in the context of modern imaging and
      neo-adjuvant treatment: 'y''u' and 'p' need 'mr' and 'ct'.
AB  - Recent developments in cross-sectional imaging, particularly computerized
      tomography and magnetic resonance imaging have provided increasingly accurate
      noninvasive preoperative staging, especially for rectal cancer. Image-based TNM
      staging, by definition a pathological system, has entered both the literature and
      everyday usage with no universal agreement as to the exact terminology.
      Clarification of the current terminology and suggestions to reflect recent
      developments are outlined to facilitate multidisciplinary team decision processes
      and objective stratification for entry to, and monitoring of, future clinical
      trials in rectal cancer.

PMID- 17498206
TI  - Laparoscopic ventral rectopexy, posterior colporrhaphy and vaginal sacrocolpopexy
      for the treatment of recto-genital prolapse and mechanical outlet obstruction.
AB  - OBJECTIVE: Whilst trans-abdominal fixation +/- resection offers better functional
      results and lower recurrence than perineal procedures, mesh rectopexy is
      complicated by constipation. Laparoscopic autonomic nerve-sparing, ventral
      rectopexy allows correction of the underlying abnormalities of the rectum,
      vagina, bladder and pelvic floor. METHOD: A prospective database was used to
      audit our 7-year experience of this technique. The recto-vaginal septum was
      mobilized anteriorly to the pelvic floor avoiding nerve damage. A prolene mesh
      was sutured to the ventral rectum, posterior vagina and vaginal fornix and
      secured to the sacral promontory. Patients were assessed with questionnaires and
      Cleveland Clinic scores. RESULTS: Eighty patients, six males, median age 59 years
      (range 31-90) underwent laparoscopic prolapse surgery between Jan 1997 and Dec
      2005; 55% had full thickness prolapse and 46% rectal anal intussusception. Five
      had a solitary rectal ulcer. A total of 58% had undergone previous surgery;
      hysterectomy 33%, posterior colporrhaphy 15%, posterior rectopexy 6%, Delorme's
      rectal mucosectomy 5% and Birch colposuspension 3%. Half (54%) were incontinent
      (mean Wexner score 11, range 2-17) and 31% reported symptoms of obstructed
      defecation; seven had slow transit constipation and underwent resection. The
      median operative time was 125 min (range 50-210) with one conversion. Median time
      to diet was 12 h and median length of stay 3 days (1-12). No patient has
      developed recurrent full thickness prolapse at a median follow-up of 54 months
      (30-96). Incontinence improved in 39 of 43 patients (91%); median post-operative
      Wexner score 1 (0-9). Obstructed defecation resolved in 20 of 25 patients (80%).
      Pelvic pain resolved in all but one. Complications occurred in 21%; faecal
      impaction 4%, wound infection 2%, bleeding 2%, leak 1%, chest infection 1%,
      retention 1%. Three developed minor evacuatory difficulties and two, urinary
      stress incontinence. CONCLUSION: Laparoscopic ventral rectopexy is safe with
      relatively low morbidity. In the medium-term, it provides good results for
      prolapse and associated symptoms of incontinence and obstructed defecation.

PMID- 17498207
TI  - Transcranial direct current stimulation reveals inhibitory deficiency in
      migraine.
AB  - The issue of interictal excitability of cortical neurons in migraine patients is
      controversial: some studies have reported hypo-, others hyperexcitability. The
      aim of the present study was to observe the dynamics of this basic interictal
      state by further modulating the excitability level of the visual cortex using
      transcranial direct current stimulation (tDCS) in migraineurs with and without
      aura. In healthy subjects anodal tDCS decreases, cathodal stimulation increases
      transcranial magnetic stimulation (TMS)-elicited phosphene thresholds (PT), which
      is suggested as a representative value of visual cortex excitability. Compared
      with healthy controls, migraine patients tended to show lower baseline PT values,
      but this decrease failed to reach statistical significance. Anodal stimulation
      decreased phosphene threshold in migraineurs similarly to controls, having a
      larger effect in migraineurs with aura. Cathodal stimulation had no significant
      effect in the patient groups. This result strengthens the notion of deficient
      inhibitory processes in the cortex of migraineurs, which is selectively revealed
      by activity-modulating cortical input.

PMID- 17498208
TI  - Caveolin-1 influences P2X7 receptor expression and localization in mouse lung
      alveolar epithelial cells.
AB  - The P2X7 receptor has recently been described as a marker for lung alveolar
      epithelial type I cells. Here, we demonstrate both the expression of P2X7 protein
      and its partition into lipid rafts in the mouse lung alveolar epithelial cell
      line E10. A significant degree of colocalization was observed between P2X7 and
      the raft marker protein Caveolin-1; also, P2X7 protein was associated with
      caveolae. A marked reduction in P2X7 immunoreactivity was observed in lung
      sections prepared from Caveolin-1-knockout mice, indicating that Caveolin-1
      expression was required for full expression of P2X7 protein. Indeed, suppression
      of Caveolin-1 protein expression in E10 cells using short hairpin RNAs resulted
      in a large reduction in P2X7 protein expression. Our data demonstrate a potential
      interaction between P2X7 protein and Caveolin-1 in lipid rafts, and provide a
      basis for further functional and biochemical studies to probe the physiologic
      significance of this interaction.

PMID- 17498209
TI  - Association between nasal carriage of Staphylococcus aureus and the human
      complement cascade activator serine protease C1 inhibitor (C1INH) valine vs.
      methionine polymorphism at amino acid position 480.
AB  - Staphylococcus aureus produces compounds that interfere with complement
      deposition. We hypothesized that humans have developed countermeasures to
      staphylococcal complement evasion and we screened for single nucleotide
      polymorphisms in the serine protease C1 inhibitor (C1INH) gene at amino acid
      position 480 (valine vs. methionine) and nasal carriage of S. aureus. In our
      study cohort, 38 individuals were persistently colonized by S. aureus, whereas 50
      were invariably culture-negative. A trend was observed towards an increased
      prevalence of the Val/Val genotype in noncarriers compared to persistent carriers
      (OR 0.50, P=0.07). The Val/Val genotype was significantly overrepresented in
      noncarriers compared to 463 Caucasian blood donors (OR 0.52, P=0.02). These
      findings suggest that susceptibility to S. aureus nasal carriage is associated
      with the C1INH V480M polymorphism.

PMID- 17498210
TI  - Effect of antibiotics on the bacterial population of the rabbit caecum.
AB  - The effect feeding antibiotics has on the bacterial population of the rabbit
      caecum was investigated. No changes in total volatile fatty acid production or
      total bacterial counts were observed compared with nonantibiotic treated
      controls. However, treatment with chlortetracycline resulted in an increase of
      propionate at the apparent cost of butyrate (P<0.05). Denaturing gradient gel
      electrophoresis analysis indicated that the two antibiotics that inhibit protein
      synthesis (chlortetracycline and tiamulin) exerted the most similar changes on
      the bacterial population structure, decreasing the diversity of the profiles.
      Sequence analysis of DNA from excised denaturing gradient gel electrophoresis
      bands was carried out. The majority of the sequences observed were most similar
      to bacterial sequences previously described in other gut environments, with 11%
      being most similar to those previously reported from the rabbit, and 95% of the
      sequences having 95% or greater identity to sequences already in GenBank.

PMID- 17498211
TI  - Several enzymes of the central metabolism are phosphorylated in Staphylococcus
      aureus.
AB  - Staphylococcus aureus is an important human and animal pathogen that harbors
      protein kinases. The proteins phosphorylated in this bacterium grown on glucose
      minimal medium have been in vivo labeled with[(32)P]-orthophosphate and analyzed
      by two-dimensional gel electrophoresis followed by MS. A total of 11 glycolytic
      phosphoproteins have been identified and verified. In vitro analyses have
      revealed that phosphorylation of these glycolytic enzymes is catalysed primarily
      through the activity of an endogenous serine/threonine kinase and to a lesser
      extent by a tyrosine kinase. The identification of these phosphoproteins should
      prove helpful in understanding and unravelling of the role of phosphorylation
      with respect to pathogenesis and virulence in this organism.

PMID- 17498212
TI  - Inactivation of the Hansenula polymorpha PMR1 gene affects cell viability and
      functioning of the secretory pathway.
AB  - In yeast, functions of the endoplasmic reticulum (ER) depend on the Golgi
      apparatus Ca2+ pool, which is replenished by the medial-Golgi ion pump Pmr1p.
      Here, to dissect the role of the Golgi Ca2+ pool in protein folding and
      elimination of unfolded proteins in the ER, the manifestations of the pmr1
      mutation in yeast Hansenula polymorpha were studied. The PMR1 gene was disrupted
      in a H. polymorpha diploid strain. Haploid segregants of this diploid bearing the
      disruption allele were viable, though they showed a severe growth defect on
      synthetic medium and rapidly died during storage at low temperature. Disruption
      of H. polymorpha PMR1 led to defects of the Golgi-hosted protein glycosylation
      and vacuolar protein sorting. This mutation increased the survival rate of H.
      polymorpha cells upon treatment with the proapoptotic drug amiodarone. Unlike
      Saccharomyces cerevisiae, the H. polymorpha pmr1 mutant was not hypersensitive to
      chemicals that induce the accumulation of unfolded proteins in the ER, indicating
      that the elimination of unfolded proteins from the ER was not essentially
      affected. At the same time, the pmr1 mutation improved the secretion of human
      urokinase and decreased its intracellular aggregation, indicating an influence of
      the mutation on the protein folding in the ER.

PMID- 17498213
TI  - Multigene phylogenetic analysis of the Lipomycetaceae and the proposed transfer
      of Zygozyma species to Lipomyces and Babjevia anomala to Dipodascopsis.
AB  - Phylogenetic relationships among species assigned to genera of the family
      Lipomycetaceae were determined from analysis of the nearly entire large, subunit
      rRNA gene, the small subunit rRNA gene, mitochondrial small subunit rRNA gene and
      the translation elongation factor-1alpha gene. Monophyly of the Lipomycetaceae
      was strongly supported, and currently described species appear genetically
      unique. The multigene analysis provided no support for maintaining the genera
      Kawasakia, Smithiozyma, Waltomyces or Zygozyma, and it is proposed that species
      in these genera be assigned to the genus Lipomyces. The monotypic genus Babjevia
      is a member of the Dipodascopsis clade and it is proposed to reassign Babjevia
      anomala to Dipodascopsis. The proposed changes will result in the Lipomycetaceae
      having two ascosporic genera, Lipomyces and Dipodascopsis, and the anamorphic
      genus Myxozyma.

PMID- 17498214
TI  - Evolution of the carboxylate Jen transporters in fungi.
AB  - Synteny analysis is combined with sequence similarity and motif identification to
      trace the evolution of the putative monocarboxylate (lactate/pyruvate)
      transporters Jen1p and the dicarboxylate (succinate/fumarate/malate) transporters
      Jen2p in Hemiascomycetes yeasts and Euascomycetes fungi. It is concluded that a
      precursor form of Jen1p, named here preJen1p, arose by the duplication of an
      ancestral Jen2p, during the speciation of Yarrowia lipolytica, which was
      transferred into a new syntenic context. The Jen1p transporters differentiated
      from preJen1p in Kluyveromyces lactis, before the Whole Genome Duplication (WGD),
      and are conserved as a single copy in the Saccharomyces species. In contrast, the
      ancestral Jen2p was definitively lost just prior to the WGD and is absent in
      Saccharomyces.

PMID- 17498215
TI  - Development of oxidative stress tolerance resulted in reduced ability to undergo
      morphologic transitions and decreased pathogenicity in a t-butylhydroperoxide
      tolerant mutant of Candida albicans.
AB  - We tested the hypothesis that adaptation of Candida albicans to chronic oxidative
      stress inhibits the formation of hyphae and reduces pathogenicity. Candida
      albicans cells were exposed to increasing concentrations of t-butylhydroperoxide
      (tBOOH), a lipid peroxidation-accelerating agent, and mutants with heritable
      tBOOH tolerance were isolated. Hypha formation by the mutants was negligible on
      Spider agar, indicating that the development of oxidative stress tolerance
      prevented Candida cells from undergoing dimorphic switches. One of the mutants,
      C. albicans AF06, was five times less pathogenic in mice than its parental
      strain, due to its reduced germ tube-, pseudohypha- and hypha-forming capability,
      and decreased phospholipase secretion. An increased oxidative stress tolerance
      may therefore be disadvantageous when this pathogen leaves blood vessels and
      invades deep organs. The AF06 mutant was characterized by high intracellular
      concentrations of endogenous oxidants, reduced monounsaturated and
      polyunsaturated fatty acid contents, the continuous induction of the
      antioxidative defense system, decreased cytochrome c-dependent respiration, and
      increased alternative respiration. The mutation did not influence growth rate,
      cell size, cell surface, cellular ultrastructures, including mitochondria, or
      recognition by human polymorphonuclear leukocytes. The selection of oxidative
      stress-tolerant respiratory Candida mutants may also occur in vivo, when reduced
      respiration helps the fungus to cope with antimycotic agents.

PMID- 17498216
TI  - Hypogammaglobulinaemia secondary to cow-milk allergy in children under 2 years of
      age.
AB  - Symptomatic hypogammaglobulinaemia in children younger than 2 years of age was
      studied to rule out a primary immunodeficiency. Thirty-four patients were
      referred to the Immunology Service to study the hypogammaglobulinaemia-associated
      clinical picture. Food allergy was documented in 10 patients by personal and
      familial history, presence of specific immunoglobulin E (IgE) and elevated total
      serum IgE levels. Coeliac disease and human immunodeficiency virus infection were
      also ruled out. Protein loss through stools was assessed by clearance of alpha1
      antitrypsin (AAT). Serum immunoglobulin levels were determined by nephelometry
      and functional antibodies were studied by enzyme-linked immunosorbent assay. The
      cellular immune response was assessed by in vitro lymphocyte proliferation in
      response to mitogens and cell subsets were analysed by flow cytometry. In five
      patients of the 10 patients we suspected a protein loss through the mucosa. Four
      of these five patients showed an increased AAT and the other showed an extensive
      cutaneous lesion. Immunological studies revealed normal antibody function, in
      vitro lymphoproliferative responses and cell numbers in four of the 5 patients.
      One patient showed abnormally low numbers of CD4(+) T cells as well as a
      defective proliferative response to mitogens. After diagnosis of cow milk
      allergy, milk was replaced with infant milk formula containing hydrolysed
      proteins. Recovery of immunoglobulin values and clinical resolution were
      achieved. Hypogammaglobulinaemia during early childhood in some children may be
      secondary to cow milk allergy, and immunoglobulins and cells may leak through the
      inflamed mucosa. Resolution of symptoms as well as normalization of
      immunoglobulin values may be easily achieved by avoidance of the offending
      allergen.

PMID- 17498217
TI  - An intracellular motif of P2X(3) receptors is required for functional cross-talk
      with GABA(A) receptors in nociceptive DRG neurons.
AB  - Functional cross-talk between structurally unrelated P2X ATP receptors and
      members of the 'cys-loop' receptor-channel superfamily represents a recently
      discovered mechanism for rapid modulation of information processing. The extent
      and the mechanism of the inhibitory cross-talks between these two classes of
      ionotropic receptors remain poorly understood, however. Both ionic and molecular
      coupling were proposed to explain cross-inhibition between P2X subtypes and
      GABA(A) receptors, suggesting a P2X subunit-dependent mechanism. We show here
      that cross-inhibition between neuronal P2X(3) or P2X(2+3) and GABA(A) receptors
      does not depend on chloride and calcium ions. We identified an intracellular
      QST(386-388) motif in P2X(3) subunits which is required for the functional
      coupling with GABA(A) receptors. Moreover the cross-inhibition between native
      P2X(3) and GABA receptors in cultured rat dorsal root ganglia (DRG) neurons is
      abolished by infusion of a peptide containing the QST motif as well as by viral
      expression of the main intracellular loop of GABA(A)beta3 subunits. We provide
      evidence that P2X(3) and GABA(A) receptors are colocalized in the soma and
      central processes of nociceptive DRG neurons, suggesting that specific
      intracellular P2X(3)-GABA(A) subunit interactions underlie a pre-synaptic cross
      talk that might contribute to the regulation of sensory synaptic transmission in
      the spinal cord.

PMID- 17498218
TI  - What are the risk factors and settings for non-alcoholic fatty liver disease in
      Asia-Pacific?
AB  - The risk factors and settings for non-alcoholic fatty liver disease (NAFLD) in
      Asians are reviewed comprehensively. Based particularly on large community-based
      studies using ultrasonography, case-control series and prospective longitudinal
      studies, the prevalence of NAFLD in Asia is between 12% and 24%, depending on
      age, gender, locality and ethnicity. Further, the prevalence in China and Japan
      has nearly doubled in the last 10-15 years. A detailed analysis of these data
      shows that NAFLD risk factors for Asians resemble those in the West for age at
      presentation, prevalence of type 2 diabetes mellitus (T2DM) and hyperlipidemia.
      The apparent differences in prevalence of central obesity and overall obesity are
      related to criteria used to define waist circumference and body mass index (BMI),
      respectively. The strongest associations are with components of the metabolic
      syndrome, particularly the combined presence of central obesity and obesity. Non
      alcoholic fatty liver disease appears to be associated with long-standing insulin
      resistance and likely represents the hepatic manifestation of metabolic syndrome.
      Not surprisingly therefore, Asians with NAFLD are at high risk of developing
      diabetes and cardiovascular disease. Conversely, metabolic syndrome may precede
      the diagnosis of NAFLD. The increasing prevalence of obesity, coupled with T2DM,
      dyslipidemia, hypertension and ultimately metabolic syndrome puts more than half
      the world's population at risk of developing NAFLD/non-alcoholic
      steatohepatitis/cirrhosis in the coming decades. Public health initiatives are
      clearly imperative to halt or reverse the global 'diabesity' pandemic, the
      underlying basis of NAFLD and metabolic syndrome. In addition, a perspective of
      NAFLD beyond its hepatic consequences is now warranted; this needs to be
      considered in relation to management guidelines for affected individuals.

PMID- 17498219
TI  - Decreased intrahepatic response to alpha(1)-adrenergic agonists in
      lipopolysaccharide-treated rats is located in the sinusoidal area and depends on
      Kupffer cell function.
AB  - BACKGROUND AND AIM: Livers from lipopolysaccharide-treated rats have a decreased
      vascular response to alpha(1)-adrenergic agonists due to an increased production
      of nitric oxide. Kupffer cells play a central role in the development of
      intrahepatic microvascular abnormalities during endotoxemia. We investigated the
      role of Kupffer cells in the intrahepatic vascular tone control in normal and
      endotoxemic rats. METHOD: Twenty-four hours after pretreatment with gadolinium
      chloride (to eliminate/inactivate Kupffer cells) or saline, rats were treated
      with lipopolysaccharide or a second dose of saline. Six hours later, rats (under
      deep anesthesia) were submitted to liver perfusion with Krebs-Henseleit solution
      using a system that allowed the measurement of both perfusion and sinusoidal
      pressures. Dose-response curves to methoxamine (alpha(1)-adrenergic agonist) were
      obtained in the absence or the presence of the nitric oxide synthase inhibitor N
      monomethyl-L-arginine. RESULTS: Pretreatment with gadolinium did not change the
      intrahepatic vascular response to methoxamine in normal livers. Livers from
      lipopolysaccharide-treated rats showed a decreased sinusoidal vascular response
      to methoxamine and a 10-fold increase in nitric oxide production during liver
      perfusion. Either pretreatment with gadolinium or the presence of N-monomethyl-L
      arginine in the perfusate restored the response to methoxamine and decreased the
      nitric oxide overproduction by more than 50%. CONCLUSIONS: Kupffer cells neither
      mediate nor modulate the intrahepatic vascular response to alpha(1)-adrenergic
      agonists in normal livers. Reduction in intrahepatic vascular response to
      alpha(1)-adrenergic agonists in livers from lipopolysaccharide-treated rats is
      located in the sinusoidal area and depends on Kupffer cell function.

PMID- 17498220
TI  - Do young hepatocellular carcinoma patients with relatively good liver function
      have poorer outcomes than elderly patients?
AB  - BACKGROUND AND AIM: The risk of hepatocellular carcinoma (HCC) is known to be age
      dependent; the influence of age on prognosis is, however, controversial. The aim
      of this study was to compare the tumor characteristics and survival rates of
      young and old HCC patients, with respect to tumor stage. METHODS: We reviewed the
      clinical data and survival times of 71 young HCC patients from 1987 to 2003 and
      compared these with those of their older counterparts (n = 239). Patients were
      categorized into three age groups: group A, age <30 years (n = 71); group B, age
      >/=30 to <61 years (n = 168); and group C, age >/=61 years (n = 81). Kaplan-Meier
      methods and Cox proportional hazards regression were used to analyze survival.
      RESULTS: The overall survival time of group A was shorter than groups B or C (P =
      0.0071). Survival was not different in the three groups in subgroup analysis
      according to several tumor staging systems (e.g. Japan Integrated Staging score,
      Cancer of the Liver Italian Program scoring system and Barcelona Clinic Liver
      Cancer staging classification). The multivariate hazard ratio of group B was
      0.840 (95% confidence interval [CI] 0.490-1.440) and that of group C was 0.770
      (95% CI 0.410-1.446) in reference to group A. CONCLUSIONS: Young HCC patients
      showed a poorer prognosis than older HCC patients because they have a more
      advanced tumor stage at diagnosis. However, age was not an independent prognostic
      factor when stages were matched. Therefore, we suggest that periodic surveillance
      in young chronic hepatitis B virus carriers would improve outcomes.

PMID- 17498221
TI  - Baseline cholesterol is associated with the response to antiviral therapy in
      chronic hepatitis C.
AB  - BACKGROUND: Hepatitis C virus (HCV) partially interacts with low-density
      lipoprotein (LDL) receptors, suggesting a role for lipids in regulating HCV
      clearance. Our aim was to study if baseline lipids can discriminate responders
      from non-responders among patients with HCV infection. METHODS: A total of 109
      HCV patients were studied. Laboratory measurements included serum lipids,
      aminotransferases and viral load, as well as HCV genotype determinations.
      RESULTS: Responders (n = 53) had significantly higher serum baseline levels of
      total cholesterol, LDL cholesterol and apolipoprotein B compared to non
      responders (n = 56). Multivariate logistic regression analysis showed that a 10
      mg/dL increase in total cholesterol was associated with 3.02 higher odds of
      responding to treatment (95% CI 1.74-5.32, P < 0.001), while a 10 mg/dL increase
      in apolipoprotein B levels was associated with 1.81 higher odds of responding to
      treatment (95% CI 1.37-2.54, P < 0.001), after adjustment for age, sex, body mass
      index (BMI), smoking habits, baseline viral load, liver histology and
      administration of pegylated interferon. An inverse association between BMI and
      response to treatment was also evident (adjusted odds ratio 0.73, 95% CI 0.55
      0.96; P = 0.03). CONCLUSION: Baseline serum total cholesterol levels and BMI
      could be helpful in discriminating responders to antiviral therapy among patients
      with HCV infection.

PMID- 17498222
TI  - Effect of cholesterol, cholic acid and cholestyramine administration on the
      intestinal mRNA expressions related to cholesterol and bile acid metabolism in
      the rat.
AB  - BACKGROUND AND AIM: To evaluate the importance of cholesterol and bile acid
      concentrations in the intestinal lumen to cholesterol homeostasis, we
      investigated the effect of cholesterol-, bile salt- or cholestyramine
      administration on the regulation of intestinal mRNA related to cholesterol and
      bile acid metabolism. METHODS: Male Wistar rats fed on standard laboratory chow
      (AIN-93) were allocated into four experimental groups: (i) control group; (ii)
      cholesterol group (CH), which was fed cholesterol in diet (2% [w/w]) for 14 days;
      (iii) cholic acid (CA) group, which was fed CA in diet (1% [w/w]) for 14 days;
      (iv) cholestyramine (CT) group, which was fed CT in diet (5% [w/w]) for 14 days.
      Blood, liver and small intestine were obtained after 14 days. Serum lipids and
      bile acids were measured by colorimetric assays, and hepatic and intestinal mRNA
      relating to lipid and bile acid metabolism was studied by reverse transcription
      polymerase chain reaction. RESULTS: Intestinal ABCG8, liver X receptor alpha,
      small heterodimer partner (SHP) and sterol regulatory element binding protein 1c
      (SREBP-1c) mRNA expressions were markedly increased in the CH group. Intestinal
      multidrug resistance associated protein (MRP) 2 and MRP3 mRNA expressions were
      markedly increased in the CA group. In the CT group intestinal MRP2, ABCG5,
      ABCG8, SHP and SREBP-1c mRNA expressions were markedly decreased. CONCLUSION: The
      bile acid availability in the intestinal lumen alters the expression of various
      intestinal mRNA relating to not only bile acid metabolism, but also lipid
      metabolism. Though the mechanism of the intestinal SHP elevation is unclear,
      cholesterol feeding may affect the intestinal bile acid metabolism via intestinal
      SHP expression.

PMID- 17498223
TI  - Semantic transparency and masked morphological priming: an ERP investigation.
AB  - The role of semantics in the segmentation of morphologically complex words was
      examined using event-related potentials (ERPs) recorded to target words primed by
      semantically transparent (hunter-hunt,) opaque (corner-corn), and
      orthographically related (scandal-scan) masked primes. Behavioral data showed
      that only transparent items gave rise to priming. The ERP data showed both N250
      and the N400 effects with transparent items generating greater priming than
      orthographic or opaque. Furthermore, priming effects across conditions revealed
      the existence of a significant linear trend, with transparent items showing the
      greatest effects and orthographic items the smallest, suggesting that these
      priming effects vary as a function of morphological structure and semantic
      transparency. The results are discussed in terms of a model of morphological
      processing.

PMID- 17498224
TI  - Impact of NOD2/CARD15 haplotypes on the outcome after kidney transplantation.
AB  - Chronic allograft nephropathy and (cardiovascular) death with functioning graft
      are major causes of late graft loss. NOD2/CARD15 (nucleotide oligomerization
      domain-2/caspase-recruiting activating domain-15), an intracellular receptor that
      is part of the innate immunity repertoire, has convincingly been shown to be
      involved in infection/inflammation-associated diseases. Specifically, NOD2/CARD15
      polymorphisms are clearly associated with Crohn's disease and transplant
      associated mortality after bone marrow transplantation. The aim of this study was
      to clarify the relevance of NOD2/CARD15-haplotypes in kidney transplantation.
      Three hundred fifty-two patients receiving their first kidney transplant were
      genotyped for the three major NOD2/CARD15 polymorphisms, R702W, G908R, and 1007fs
      with subsequent reconstruction of the different haplotypes. Four different
      NOD2/CARD15 haplotypes were observed in our population [CG(-): 89.8%, CGC: 3.5%,
      CC(-): 1.6%, TG(-): 5.1%]. After stratifying the different haplotypes into
      diplotypes (wild type: CG(-)/CG(-), n=284, mutated haplotype, n=68) we found a
      significant association with all-cause and cardiovascular mortality, also after
      adjusting to different covariates, and (only) in univariate analysis with graft
      survival. In conclusion, we found different effects of the NOD2/CARD15 haplotypes
      on disorders, like cardiovascular and all-cause mortality,which may be considered
      at least in part as chronic inflammation-driven. Further studies are needed to
      confirm and work out the association between these disorders and the NOD2/CARD15
      haplotypes.

PMID- 17498226
TI  - Population differentiation and species cohesion in two closely related plants
      adapted to neotropical high-altitude 'inselbergs', Alcantarea imperialis and
      Alcantarea geniculata (Bromeliaceae).
AB  - Isolated granitic rock outcrops or 'inselbergs' may provide a window into the
      molecular ecology and genetics of continental radiations under simplified
      conditions, in analogy to the use of oceanic islands in studies of species
      radiations. Patterns of variability and gene flow in inselberg species have never
      been thoroughly evaluated in comparison to related taxa with more continuous
      distribution ranges, or to other species in the same kingdom in general. We use
      nuclear microsatellites to study population differentiation and gene flow in two
      diploid, perennial plants adapted to high-altitude neotropical inselbergs,
      Alcantarea imperialis and Alcantarea geniculata (Bromeliaceae). Population
      differentiation is pronounced in both taxa, especially in A. imperialis. Gene
      flow in this species is considerably lower than expected from the literature on
      plants in general and Bromeliaceae in particular, and too low to prevent
      differentiation due to drift (N(e)m < 1), unless selection coefficients/effect
      sizes of favourable alleles are great enough to maintain species cohesion. Low
      gene flow in A. imperialis indicates that the ability of pollinating bats to
      promote gene exchange between inselbergs is smaller than previously assumed.
      Population subdivision in one inselberg population of A. imperialis appears to be
      associated with the presence of two colour morphs that differ in the coloration
      of rosettes and bracts. Our results indicate a high potential for inselbergs as
      venues for studies of the molecular ecology and genetics of continental
      radiations, such as the one that gave rise to the extraordinary diversity of
      adaptive strategies and phenotypes seen in Bromeliaceae.

PMID- 17498227
TI  - Detecting genetic structure in migrating bowhead whales off the coast of Barrow,
      Alaska.
AB  - We develop a general framework for analysing and testing genetic structure within
      a migratory assemblage that is based on measures of genetic differences between
      individuals. We demonstrate this method using microsatellite DNA data from the
      Bering-Chukchi-Beaufort stock of bowhead whales (Balaena mysticetus), sampled via
      Inuit hunting during the spring and autumn migration off Barrow, Alaska. This
      study includes a number of covariates such as whale ages and the time separation
      between captures. Applying the method to a sample of 117 bowhead whales, we use
      permutation methods to test for temporal trends in genetic differences that can
      be ascribed to age-related effects or to timing of catches during the seasons.
      The results reveal a pattern with elevated genetic differences among whales
      caught about a week apart, and are statistically significant for the autumn
      migration. In contrast, we find no effects of time of birth or age-difference on
      genetic differences. We discuss possible explanations for the results, including
      population substructuring, demographic consequences of historical
      overexploitation, and social structuring during migration.

PMID- 17498228
TI  - Genetic diversity and population size: island populations of the common shrew,
      Sorex araneus.
AB  - Populations of many species are currently being fragmented and reduced by human
      interactions. These processes will tend to reduce genetic diversity within
      populations and reduce individual heterozygosities because of genetic drift,
      inbreeding and reduced migration. Conservation biologists need to know the effect
      of population size on genetic diversity, as this is likely to influence a
      population's ability to persist. Island populations represent an ideal natural
      experiment with which to study this problem. In a study of common shrews (Sorex
      araneus) on offshore Scottish islands, 497 individuals from 13 islands of
      different sizes and 6 regions on the mainland were trapped and genotyped at eight
      microsatellite loci. Previous genetic work had revealed that most of the islands
      in this study were highly genetically divergent from one another and the
      mainland. We found that most of the islands exhibited lower genetic diversity
      than the mainland populations. In the island populations, mean expected
      heterozygosity, mean observed heterozygosity and mean allelic richness were
      significantly positively correlated with log island size and log population size,
      which were estimated using habitat population density data and application of a
      Geographic Information System.

PMID- 17498229
TI  - Complex hybridization dynamics between golden-winged and blue-winged warblers
      (Vermivora chrysoptera and Vermivora pinus) revealed by AFLP, microsatellite,
      intron and mtDNA markers.
AB  - Blue-winged (Vermivora pinus) and golden-winged warblers (Vermivora chrysoptera)
      have an extensive mosaic hybrid zone in eastern North America. Over the past
      century, the general trajectory has been a rapid replacement of chrysoptera by
      pinus in a broad, northwardly moving area of contact. Previous mtDNA-based
      studies on these species' hybridization dynamics have yielded variable results:
      asymmetric and rapid introgression from pinus into chrysoptera in some areas and
      bidirectional maternal gene flow in others. To further explore the hybridization
      genetics of this otherwise well-studied complex, we surveyed variation in three
      nuclear DNA marker types--microsatellites, introns, and a panel of amplified
      fragment length polymorphisms (AFLPs)--with the goal of generating a multilocus
      assay of hybrid introgression. All markers were first tested on birds from
      phenotypically and mitochondrially pure parental-type populations from outside
      the hybrid zone. Searches for private alleles and assignment test approaches
      found no combination of microsatellite or intron markers that could separate the
      parental populations, but seven AFLP characters exhibited significant frequency
      differences among them. We then used the AFLP markers to examine the extent and
      pattern of introgression in a population where pinus-phenotype individuals have
      recently invaded a region that previously supported only a chrysoptera-phenotype
      population. Despite the low frequency of phenotypic hybrids at this location, the
      AFLP data suggest that almost a third of the phenotypically pure chrysoptera have
      introgressed genotypes, indicating the presence of substantial cryptic
      hybridization in the history of this species. The evidence for extensive cryptic
      introgression, combined with the lack of differentiation at other nuclear loci,
      cautions against hybrid assessments based on single markers or on phenotypic
      traits that are likely to be determined by a small number of loci. Considered in
      concert, these results from four classes of molecular markers indicate that pinus
      and chrysoptera are surprisingly weakly differentiated and that far fewer
      genetically 'pure' populations of chrysoptera may exist than previously assumed,
      two findings with broad implications for the conservation of this rapidly
      declining taxon.

PMID- 17498230
TI  - A new individual-based spatial approach for identifying genetic discontinuities
      in natural populations.
AB  - The population concept is central in evolutionary and conservation biology, but
      identifying the boundaries of natural populations is often challenging. Here, we
      present a new approach for assessing spatial genetic structure without the a
      priori assumptions on the locations of populations made by adopting an individual
      centred approach. Our method is based on assignment tests applied in a moving
      window over an extensively sampled study area. For each individual, a spatially
      explicit probability surface is constructed, showing the estimated probability of
      finding its multilocus genotype across the landscape, and identifying putative
      migrants. Population boundaries are localized by estimating the mean slope of
      these probability surfaces over all individuals to identify areas with genetic
      discontinuities. The significance of the genetic discontinuities is assessed by
      permutation tests. This new approach has the potential to reveal cryptic
      population structure and to improve our ability to understand gene flow dynamics
      across landscapes. We illustrate our approach by simulations and by analysing two
      empirical datasets: microsatellite data of Ursus arctos in Scandinavia, and
      amplified fragment length polymorphism (AFLP) data of Rhododendron ferrugineum in
      the Alps.

PMID- 17498231
TI  - The geography of diversification in mutualistic ants: a gene's-eye view into the
      Neogene history of Sundaland rain forests.
AB  - We investigate the geographical and historical context of diversification in a
      complex of mutualistic Crematogaster ants living in Macaranga trees in the
      equatorial rain forests of Southeast Asia. Using mitochondrial DNA from 433 ant
      colonies collected from 32 locations spanning Borneo, Malaya and Sumatra, we
      infer branching relationships, patterns of genetic diversity and population
      history. We reconstruct a time frame for the ants' diversification and
      demographic expansions, and identify areas that might have been refugia or
      centres of diversification. Seventeen operational lineages are identified, most
      of which can be distinguished by host preference and geographical range. The ants
      first diversified 16-20 Ma, not long after the onset of the everwet forests in
      Sundaland, and achieved most of their taxonomic diversity during the Pliocene.
      Pleistocene demographic expansions are inferred for several of the younger
      lineages. Phylogenetic relationships suggest a Bornean cradle and major axis of
      diversification. Taxonomic diversity tends to be associated with mountain ranges;
      in Borneo, it is greatest in the Crocker Range of Sabah and concentrated also in
      other parts of the northern northwest coast. Within-lineage genetic diversity in
      Malaya and Sumatra tends to also coincide with mountain ranges. A series of
      disjunct and restricted distributions spanning northern northwest Borneo and the
      major mountain ranges of Malaya and Sumatra, seen in three pairs of sister
      lineages, further suggests that these regions were rain-forest refuges during
      drier climatic phases of the Pleistocene. Results are discussed in the context of
      the history of Sundaland's rain forests.

PMID- 17498232
TI  - Population structure and the co-evolution between social parasites and their
      hosts.
AB  - Co-evolutionary trajectories of host-parasite interactions are strongly affected
      by the antagonists' evolutionary potential, which in turn depends on population
      sizes as well as levels of recombination, mutation, and gene flow. Under similar
      selection pressures, the opponent with the higher evolutionary rate is expected
      to lead the co-evolutionary arms race and to develop local adaptations. Here, we
      use mitochondrial DNA sequence data and microsatellite markers to assess the
      amount of genetic variability and levels of gene flow in two host-parasite
      systems, each consisting of an ant social parasite--the European slavemaker
      Harpagoxenus sublaevis and the North American slavemaker Protomognathus
      americanus--and its two main host species. Our population genetic analyses
      revealed limited gene flow between individual populations of both host and
      parasite species, allowing for a geographic mosaic of co-evolution. In a between
      system comparison, we found less genetic variability and more pronounced
      structure in Europe, where previous behavioural studies demonstrated strong local
      adaptation. Within the European host-parasite system, the larger host species
      Leptothorax acervorum exhibited higher levels of both genetic variability and
      gene flow, and previous field data showed that it is less affected by the social
      parasite H. sublaevis than the smaller host Leptothorax muscorum, which has
      genetically depleted and isolated populations. In North America, the parasite P.
      americanus showed higher levels of gene flow between sites, but overall less
      genetic diversity than its hyper-variable main host species, Temnothorax
      longispinosus. Interestingly, recent ecological and chemical studies demonstrated
      adaptation of P. americanus to local host populations, indicating the importance
      of migration in co-evolutionary interactions.

PMID- 17498233
TI  - Dispersal differences predict population genetic structure in Mormon crickets.
AB  - Research investigating the geographical context of speciation has primarily
      focused on abiotic factors such as the role of Pleistocene glacial cycles, or
      geotectonic events. Few study systems allow a direct comparison of how biological
      differences, such as dispersal behaviour, affect population genetic structure of
      organisms that were subdivided during the Pleistocene. Mormon crickets exist in
      solitary and gregarious 'phases', which broadly correspond with an east-west
      mtDNA division across the Rocky Mountains. Gregarious individuals form bands that
      can move up to 2 km daily. This study assessed whether population genetic
      structure results mainly from deep Pleistocene vicariance or if we can also
      detect more recent genetic patterns due to phase and dispersal differences
      superimposed on the older, deeper divisions. We found that separation in refugia
      was a more important influence on genetic divergence than phase, with the Rockies
      acting as a barrier that separated Mormon cricket populations into eastern and
      western refugia during Pleistocene glacial cycles. However, patterns of isolation
      by distance differ between eastern and western clades for both mitochondrial and
      nuclear DNA, with greater divergence within the eastern, solitary clade. An mtDNA
      haplotype mismatch distribution is compatible with historical population
      expansion in the western clade but not in the eastern clade. A persistent (and
      possibly sex-biased) difference in dispersal ability has most likely influenced
      the greater population genetic structure seen in the eastern clade, emphasizing
      the importance of the interaction of Quaternary climate fluctuations and
      geography with biotic factors in producing the patterns of genetic subdivision
      observed today.

PMID- 17498234
TI  - Bread, beer and wine: Saccharomyces cerevisiae diversity reflects human history.
AB  - Fermented beverages and foods have played a significant role in most societies
      worldwide for millennia. To better understand how the yeast species Saccharomyces
      cerevisiae, the main fermenting agent, evolved along this historical and
      expansion process, we analysed the genetic diversity among 651 strains from 56
      different geographical origins, worldwide. Their genotyping at 12 microsatellite
      loci revealed 575 distinct genotypes organized in subgroups of yeast types, i.e.
      bread, beer, wine, sake. Some of these groups presented unexpected relatedness:
      Bread strains displayed a combination of alleles intermediate between beer and
      wine strains, and strains used for rice wine and sake were most closely related
      to beer and bread strains. However, up to 28% of genetic diversity between these
      technological groups was associated with geographical differences which suggests
      local domestications. Focusing on wine yeasts, a group of Lebanese strains were
      basal in an F(ST) tree, suggesting a Mesopotamia-based origin of most wine
      strains. In Europe, migration of wine strains occurred through the Danube Valley,
      and around the Mediterranean Sea. An approximate Bayesian computation approach
      suggested a postglacial divergence (most probable period 10,000-12,000 bp). As
      our results suggest intimate association between man and wine yeast across
      centuries, we hypothesize that yeast followed man and vine migrations as a
      commensal member of grapevine flora.

PMID- 17498236
TI  - Phylogeography of the piranha genera Serrasalmus and Pygocentrus: implications
      for the diversification of the Neotropical ichthyofauna.
AB  - The phylogenetic relationships within the piranhas were assessed using
      mitochondrial sequences with the aim of testing several hypotheses proposed to
      explain the origin of Neotropical diversity (palaeogeography, hydrogeology and
      museum hypotheses). Sequences of the ribosomal 16S gene (510 bp) and control
      region (980 bp) were obtained from 15 localities throughout the main South
      American rivers for 21 of the 28 extant piranha species. The results indicate
      that the genus Serrasalmus is monophyletic and comprises three major clades. The
      phylogeographical analyses of these clades allowed the identification of five
      vicariant events, extensive dispersal and four lineage duplications suggesting
      the occurrence of sympatric speciation. Biogeographical patterns are consistent
      with the prediction made by the museum hypothesis that lineages from the
      Precambrian shields are older than those from the lowlands of the Amazon. The
      vicariant events inferred here match the distribution of the palaeoarches and
      several postdispersal speciation events are identified, thereby matching the
      predictions of the palaeogeography and hydrogeology hypotheses, respectively.
      Molecular clock calibration of the control region sequences indicates that the
      main lineages differentiated from their most recent common ancestor at 9 million
      years ago in the proto Amazon-Orinoco and the present rate of diversification is
      the highest reported to date for large carnivorous Characiformes. The present
      results emphasize that an interaction among geology, sea-level changes, and
      hydrography created opportunities for cladogenesis in the piranhas at different
      temporal and geographical scales.

PMID- 17498235
TI  - Longitudinal range expansion and cryptic eastern species in the western
      Palaearctic oak gallwasp, Andricus coriarius.
AB  - The oak gallwasp Andricus coriarius is distributed across the Western Palaearctic
      from Morocco to Iran. It belongs to a clade of host-alternating Andricus species
      that requires host oaks in two sections of Quercus subgenus Quercus to complete
      its lifecycle, a requirement that has restricted the historic distribution and
      dispersal of members of this clade. Here we present nuclear and mitochondrial
      sequence evidence from the entire geographic range of A. coriarius to investigate
      the genetic legacy of longitudinal range expansion. We show A. coriarius as
      currently understood to be para- or polyphyletic, with three evolutionarily
      independent (but partially sympatric) lineages that diverged c. 10 million years
      ago (mya). The similarities in gall structure that have justified recognition of
      single species to date thus represent either strong conservation of an ancestral
      state or striking convergence. All three lineages originated in areas to the east
      of Europe, underlining the significance of Turkey, Iran and the Levant as
      'cradles' of gallwasp evolution. One of the three lineages gave rise to all
      European populations, and range expansion from a putative Eastern origin to the
      present distribution is predicted to have occurred around 1.6 mya.

PMID- 17498237
TI  - Range-wide phylogeography and gene zones in Pinus pinaster Ait. revealed by
      chloroplast microsatellite markers.
AB  - Some 1339 trees from 48 Pinus pinaster stands were characterized by five
      chloroplast microsatellites, detecting a total of 103 distinct haplotypes.
      Frequencies for the 16 most abundant haplotypes (p(k) > 0.01) were spatially
      interpolated over a lattice made by 430 grid points. Fitting of spatially
      interpolated values on raw haplotype frequencies at the same geographical
      location was tested by regression analysis. A range-wide 'diversity map' based on
      interpolated haplotype frequencies allowed the identification of one 'hotspot' of
      diversity in central and southeastern Spain, and two areas of low haplotypic
      diversity located in the western Iberian peninsula and Morocco. Principal
      component analysis (PCA) carried out on haplotypes frequency surfaces allowed the
      construction of a colour-based 'synthetic' map of the first three PC components,
      enabling the detection of the main range-scale genetic trends and the
      identification of three main 'gene pools' for the species: (i) a 'southeastern'
      gene pool, including southeastern France, Italy, Corsica, Sardinia, Pantelleria
      and northern Africa; (ii) an 'Atlantic' gene pool, including all the western
      areas of the Iberian peninsula; and (iii) a 'central' gene pool, located in
      southeastern Spain. Multivariate and AMOVA analyses carried out on interpolated
      grid point frequency values revealed the existence of eight major clusters ('gene
      zones'), whose genetic relationships were related with the history of the
      species. In addition, demographic models showed more ancient expansions in the
      eastern and southern ranges of maritime pine probably associated to early
      postglacial recolonization. The delineation of the gene zones provides a baseline
      for designing conservation areas in this key Mediterranean pine.

PMID- 17498238
TI  - Ecology matters: Atlantic-Mediterranean disjunction in the sand-dune shrub
      Armeria pungens (Plumbaginaceae).
AB  - Inferring the evolutionary history of Mediterranean plant lineages from current
      genetic, distributional and taxonomic patterns is complex because of a number of
      palaeoclimatic and geological interconnected factors together with landscape
      heterogeneity and human influence. Therefore, choosing spatially simplified
      systems as study groups is a suitable approach. An amplified fragment length
      polymorphism (AFLP) study using two restriction enzyme combinations (EcoRI/MseI
      and KpnI/MseI) was carried out to estimate the structure of genetic variation
      throughout the range of Armeria pungens. This species has a West Iberian
      Corso/Sardinian disjunct distribution on coastal sand-dune ecosystems. Bayesian,
      amova and genetic distance analyses of the AFLP data revealed the same
      distinguishable genetic groups, which do not match the main geographical
      disjunction. Corso-Sardinian populations were found to be genetically closer to
      southwest Portuguese than to those from the Gulf of Cadiz (the closest
      geographically). Eastwards long-distance dispersal is therefore invoked to
      explain this geographical disjunction. A GIS analysis based on bioclimatic
      envelope modelling aiming to characterize the current locations of A. pungens
      found strong similarities between the Portugal and Corsica-Sardinia sites and
      less so between these areas and the Gulf of Cadiz. This coincident pattern
      between AFLP and climatic data suggests that the geographical disjunction is
      better explained by climatic factors than by the likeliness of a stochastic
      dispersal event. Such a combined phylogeographical-GIS modelling approach proves
      to be enlightening in reconstructing the evolutionary history of plant species.

PMID- 17498239
TI  - Mitochondrial DNA phylogeography and mating compatibility reveal marked genetic
      structuring and speciation in the NE Atlantic bryozoan Celleporella hyalina.
AB  - The marine bryozoan Celleporella hyalina is a species complex composed of many
      highly divergent and mostly allopatric genetic lineages that are reproductively
      isolated but share a remarkably similar morphology. One such lineage commonly
      encrusts macroalgae throughout the NE Atlantic coast. To explore the processes
      leading to geographical diversification, reproductive isolation and speciation in
      this taxon, we (i) investigated NE Atlantic C. hyalina mitochondrial DNA
      phylogeography, and (ii) used breeding trials between geographical isolates to
      ascertain reproductive isolation. We find that haplotype diversity is
      geographically variable and there is a strong population structure, with
      significant isolation by distance. NE Atlantic C. hyalina is structured into two
      main parapatric lineages that appear to have had independent Pleistocene
      histories. Range expansions have resulted in two contact zones in Spain and W
      Ireland. Lineage 1 is found from Ireland to Spain and has low haplotype
      diversity, with closely related haplotypes, suggesting a recent population
      expansion into the Irish Sea, S Ireland, S England and Spain. Lineage 2 is found
      from Iceland to Spain and has high haplotype diversity. Complete reproductive
      isolation was found between some geographical isolates representing both
      lineages, whereas it was incomplete or asymmetric between others, suggesting
      these latter phylogeographical groups probably represent incipient species. The
      phylogeographical distribution of NE Atlantic C. hyalina does not fall easily
      into a pattern of southern refugia, and we discuss likely differences between
      terrestrial and marine system responses to Pleistocene glacial cycles.

PMID- 17498240
TI  - Non-proteolytic neurotrophic effects of tissue plasminogen activator on cultured
      mouse cerebrocortical neurons.
AB  - Most biological effects of tissue plasminogen activator (tPA), such as
      fibrinolysis, are mediated by its protease activity. Recent studies, however,
      have demonstrated that tPA also has several protease-independent effects such as:
      neuroprotection, microglial activation, and promoting LTP formation. In order to
      gain a better understanding of how tPA affects neurons, we examined neurite
      outgrowth and cell survival in low density cerebrocortical neuronal culture in
      the presence of tPA. tPA enhanced neurite elongation and neuronal survival. tPA
      protease inhibitors, PAI-1 or PMSF, did not alter either effect. Consistent with
      neurotrophic effects, tPA activated Raf-K/ERK, PKC and PI3-K/Akt, 5-60 min after
      treatment. In addition, specific inhibitors of these kinases reduced tPA-induced
      neurite outgrowth. Interestingly, survival-promoting effect of tPA was attenuated
      only by PI3-K inhibitors. Activation of signaling kinases suggests that tPA
      activates an upstream membrane receptor. Thus far, three membrane proteins, low
      density lipoprotein receptor-related protein (LRP), mannose receptor (MR), and
      annexin-II (AII), have been identified to bind tPA. While inhibiting LRP or MR
      did not change tPA-induced neurite outgrowth and cell survival, inhibiting AII
      blocked neurotrophic effects of tPA. Taken together, our results indicate that
      tPA has novel, non-proteolytic neurotrophic effects on cultured cortical neurons,
      which are likely mediated by AII.

PMID- 17498241
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates the oxygen
      sensing type I (glomus) cells of rat carotid bodies via reduction of a background
      TASK-like K+ current.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient mice are
      prone to sudden neonatal death and have reduced respiratory response to hypoxia.
      Here we found that PACAP-38 elevated cytosolic [Ca(2+)] ([Ca(2+)](i)) in the
      oxygen sensing type I cells but not the glial-like type II (sustentacular) cells
      of the rat carotid body. This action of PACAP could not be mimicked by vasoactive
      intestinal peptide but was abolished by PACAP 6-38, implicating the involvement
      of PAC(1) receptors. H89, a protein kinase A (PKA) inhibitor attenuated the PACAP
      response. Simultaneous measurement of membrane potential and [Ca(2+)](i) showed
      that the PACAP-mediated [Ca(2+)](i) rise was accompanied by depolarization and
      action potential firing. Ni(2+), a blocker of voltage-gated Ca(2+) channels
      (VGCC) or the removal of extracellular Ca(2+) reversibly inhibited the PACAP
      mediated [Ca(2+)](i) rise. In the presence of tetraethylammonium (TEA) and 4
      aminopyridine (4-AP), PACAP reduced a background K(+) current. Anandamide, a
      blocker of TWIK-related acid-sensitive K(+) (TASK)-like K(+) channel, occluded
      the inhibitory action of PACAP on K(+) current. We conclude that PACAP, acting
      via the PAC(1) receptors coupled PKA pathway inhibits a TASK-like K(+) current
      and causes depolarization and VGCC activation. This stimulatory action of PACAP
      in carotid type I cells can partly account for the role of PACAP in respiratory
      disorders.

PMID- 17498242
TI  - Prognostic models in cirrhosis: an aid but not a replacement for clinical
      judgement.

PMID- 17498243
TI  - HIV/HCV co-infection: histopathologic findings, natural history, fibrosis, and
      impact of antiretroviral treatment: a review article.
AB  - Human immunodeficiency virus/hepatitis C virus (HIV/HCV) co-infection has emerged
      as a leading cause of liver morbidity in the last two decades. Liver failure is
      also frequently a cause of death in HIV/HCV co-infected patients. Highly active
      antiretroviral treatment (HAART) has revolutionized the HIV treatment, leading to
      a significantly decreased morbidity, prolonged survival, and an overall better
      outcome of HIV infection. Hepatotoxicity associated with antiretroviral
      treatment, however, has been recognized as one of the serious complications of
      the treatment. The effects of HIV infection on the natural history and
      progression of HCV-associated chronic liver disease that had been well documented
      in the pre-HAART treatment era have been changing, and there are now many
      indications that HIV/HCV co-infection should be recognized as an evolving and a
      challenging disease entity.

PMID- 17498244
TI  - Impact of non-alcoholic fatty liver disease on chronic hepatitis B.
AB  - BACKGROUND: The impact of superimposed non-alcoholic fatty liver disease (NAFLD)
      is well established in patients with chronic hepatitis C (CH-C), but the impact
      in patients with chronic hepatitis B (CH-B) is less clear. AIM: This study aims
      to evaluate the prevalence of NAFLD in patients with CH-B and the association
      with viral and host factors, particularly in patients with metabolic syndrome
      (MS). DESIGN: Data from patients with CH-B was obtained from our databases.
      Patients with excessive alcohol use were excluded. Hepatitis B virus (HBV)
      genotyping by INNO-LIPA was available for some patients. The presence of MS was
      defined according to the Adult Treatment Panel III (ATP III). All biopsies were
      read by two hepatopathologists using Metavir, modified histologic activity index
      (MHAI), as well as a NAFLD pathologic protocol. Patients were classified as (1)
      those without NAFLD; (2) those with simple hepatic steatosis; (3) and those with
      superimposed non-alcoholic steatohepatitis (NASH). Factors associated with
      superimposed NAFLD, its subtypes, and hepatic fibrosis were also analysed.
      RESULTS: Subjects included 153 HBV patients [66% male, age 50.5+/-27.5 years,
      body mass index 24.7+/-3.7 kg/m(2), waist 83.2+/-10.9 cm; 8.5% Caucasian, 67%
      Asian, aspartate aminotransferase (AST) 63.2+/-88.2 IU/l, alanine
      aminotransferase (ALT) 98.6+/-164.6 IU/l, glucose 111.6+/-50.5 mg/dl, HBV-DNA 1.8
      x 10(8)+/-1.9 x 10(6) copies/ml, 7% with MS, 13% with diabetes, 20% with arterial
      hypertension and 8.5% with dyslipidaemia]. Liver biopsy was available for 64
      subjects [19% had superimposed NAFLD, 13% had superimposed NASH, 86% had some
      degree of fibrosis, and 39% had advanced fibrosis (Ishak >3)]. Patients with HBV
      and superimposed NASH were significantly older (55 vs. 42 years, P=0.008), more
      likely to have hypertension (63% vs. 15%, P=0.006) and dyslipidaemia (50% vs. 8%,
      P=0.006), and had a larger waist circumference (92 vs. 83 cm, P=0.03). The
      presence of fibrosis was associated with higher waist circumference (84 vs. 80
      cm, P=0.03), higher HBV-DNA (1.9 x 10(8) vs. 5 x 10(6) copies/ml, P=0.005), and
      elevated ALT >40 IU/l (73.6% vs. 33.3%, P=0.02). CONCLUSIONS: The components of
      MS (obesity, hypertension, and dyslipidaemia) are associated with the presence of
      NASH in patients with CH-B. The presence of hepatic fibrosis seems to be
      associated with known host and viral factors as well as the presence of abdominal
      obesity.

PMID- 17498245
TI  - Viral load 1 week after liver transplantation, donor age and rejections correlate
      with the outcome of recurrent hepatitis C.
AB  - BACKGROUND: Early identification of patients at a higher risk of rapidly
      progressive recurrent hepatitis post liver transplantation (LT) could help to
      tailor antiviral therapy. METHODS: We studied the correlation between early post
      LT viral load and the histological and clinical outcomes of 49 consecutive
      patients (34 males, median age 55 years) in whom viraemia was monitored at days
      0, 1, 7, 30, 180 and 365 after LT. RESULTS: Hepatitis C recurred at histology in
      38 of 42 (90.5%) patients. Early viral load after LT was higher in patients with
      rapidly progressive hepatitis C recurrence (day 7 median HCV-RNA levels: 5.84 vs
      4.93 Log(10) IU/ml, P=0.003). Day 7 HCV-RNA levels >/=2.5 x 10(5) IU/ml, donor
      age >60 years and rejection episodes were independently associated with
      progression to cirrhosis within one year post-LT [P=0.018, odds ratio (OR) 27.59;
      P=0.043, OR 13.85 and P=0.048, OR 9.95, respectively]. Day 7 viraemia and
      rejection episodes were independently associated with 5-years survival. Day 7
      viraemia, in combination with acute hepatitis and/or donor age, showed 80%
      sensitivity, 94% specificity and 90.5% diagnostic accuracy to identify severe
      recurrence. CONCLUSIONS: Early post-LT HCV-RNA correlates with the severity of
      hepatitis C recurrence and in combination with donor age (>60 years) and
      rejections, identifies patients with a high risk of severe recurrence and
      candidates of cost-effective pre-emptive antiviral therapy.

PMID- 17498246
TI  - Hepatic steatosis correlates with the postoperative recurrence of hepatitis C
      virus-associated hepatocellular carcinoma.
AB  - BACKGROUND: Hepatic steatosis is a prominent feature of chronic hepatitis C.
      Hepatic steatosis was reported recently to be a risk factor for hepatitis C virus
      (HCV)-associated hepatocellular carcinoma (HCC). AIM: To investigate whether
      hepatic steatosis influences the postoperative recurrence of HCV-associated HCC.
      METHODS: A retrospective study was conducted in 88 patients undergoing curative
      resection of HCV-associated HCC. Cumulative tumour recurrence rates were compared
      between steatosis-positive and steatosis-negative patients, and the factors
      affecting intrahepatic recurrence were assessed. RESULTS: The respective tumour
      recurrence rates at 1, 3, and 5 years were 19%, 76%, and 92% in the steatosis
      positive group, and 12%, 52%, and 60% in the steatosis-negative group. The tumour
      recurrence rate of the steatosis-positive group was significantly higher than
      that of the steatosis-negative group (P=0.02). Hepatic steatosis [relative risk
      (RR)=3.31, 95% confidence intervals (CIs)=1.49-7.41, P=0.003], stage of fibrosis
      (RR=3.17, 95% CI=1.35-7.47, P=0.008), surgical procedure (RR=0.22, 95% CI=0.076
      0.64, P=0.005), number of tumours (RR=5.24, 95% CI=1.63-16.80, P=0.005), size of
      the largest tumour (RR=3.52, 95% CI=1.28-9.69, P=0.02), and vascular invasion
      (RR=2.72, 95% CI=1.32-5.59, P=0.007) were independent factors for tumour
      recurrence rate by multivariate analysis. CONCLUSIONS: Hepatic steatosis is a
      useful predictor of postoperative recurrence of HCV-related HCC.

PMID- 17498247
TI  - Hepatitis B-associated vasculitis in Alaska Natives: viral genotype, clinical and
      serologic outcome.
AB  - BACKGROUND: The highest incidence of hepatitis B virus (HBV)-associated
      vasculitis in the world has been reported in Alaska Natives. We examined the
      incidence of HBV-associated vasculitis before and after mass HBV vaccine
      immunization and the association between HBV genotype and vasculitis in a
      population-based cohort study in Alaska natives chronically infected with HBV.
      METHODS: Genotyping was performed in vasculitis cases and 644 hepatitis B
      positive controls without vasculitis using polymerase chain reaction and
      sequencing of the S gene. Occurrence of HBV vasculitis from 1974 to 2004 was
      calculated. HBV vasculitis patients and controls were also tested for basal core
      promoter and precore mutations. RESULTS: Fifteen cases of HBV-associated
      vasculitis were identified: 13 (86%) had genotype D and one each genotype A and
      F. Genotype D was more commonly found in patients with vasculitis than controls
      [odd ratio (OR)=5.9, confidence interval (95% CI) 1.2, 21.8; P<0.015).
      CONCLUSIONS: HBV-associated vasculitis was associated with genotype D.

PMID- 17498248
TI  - Analysis of the core gene of hepatitis B virus in Korean patients.
AB  - BACKGROUND/AIMS: As the core gene of hepatitis B virus (HBV) is a major
      immunological target, its mutation may evoke or evade immune clearance. We
      investigated the frequency and location of HBV core gene substitutions according
      to hepatitis B e antigen (HBeAg) status and viral replication status, and
      evaluated the association of these substitutions with the different stages of
      chronic HBV infection in Korean patients. METHODS: The study population included
      45 HBeAg-positive/DNA-positive patients (group I), 49 HBeAg-negative/DNA-positive
      patients (II) and 50 HBeAg-negative/DNA-negative patients (III). The HBV core
      gene was analysed by polymerase chain reaction (PCR) and sequencing. RESULTS: The
      frequency of core gene substitutions increased from group I to group III.
      Substitutions were commonly detected at codons 87, 97, 112 and 130. The frequency
      of substitutions at codons 87 and 112 was higher in groups II/III than in group
      I. The frequency of the codon I97F substitutions was the highest in group III.
      However, the codon 130 substitution was more frequently found in groups I/II than
      in group III. CONCLUSION: Core gene substitutions were more frequently detected
      in HBeAg-negative and/or HBV DNA-negative patients. The substitutional hot spots
      were codons 87, 97, 112 and 130; substitutions at these codons might play a role
      in immune-modulation during the course of chronic HBV infection.

PMID- 17498249
TI  - Biochemical and biophysical assessment of MTX-induced liver fibrosis in psoriasis
      patients: Fibrotest predicts the presence and Fibroscan predicts the absence of
      significant liver fibrosis.
AB  - BACKGROUND: Methotrexate (MTX) use is associated with hepatic fibrosis in
      psoriasis patients. To monitor this serial liver biopsies were performed. The
      Fibroscan and the Fibrotest are two novel, non-invasive methods that might be
      able to assess MTX-induced hepatic fibrosis. AIM: Evaluating the accuracy and
      feasibility of the Fibroscan and Fibrotest to detect significant MTX-induced
      liver fibrosis in psoriasis patients. METHODS: We assessed 24 psoriasis patients
      who had a recent liver biopsy during MTX use. The results from the Fibroscan and
      Fibrotest were compared with liver histology. RESULTS: Fibroscan values (n=20)
      ranged between 3.3 and 18.4 kPa (median value 6.4 kPa) and correctly identified
      88% of the patients without significant liver fibrosis (Metavir score <F2,
      Fibroscan</=7.1 kPa). The Fibrotest identified 83% of the patients with
      significant liver fibrosis (Metavir score >/=F2, Fibrotest >0.31). CONCLUSION: In
      this population, Fibrotest accurately predicted the presence of significant liver
      fibrosis while the Fibroscan accurately predicted the absence of significant
      liver fibrosis in MTX users. This suggests that a combination of Fibrotest and
      Fibroscan should prospectively be evaluated in monitoring and detecting
      significant MTX-induced liver fibrosis in psoriasis patients.

PMID- 17498250
TI  - Transjugular liver biopsy in patients with diffuse liver disease: comparison of
      three cores with one or two cores for accurate histological interpretation.
AB  - BACKGROUND: Transjugular liver biopsy (TJLB) can be performed to obtain more than
      two cores safely. This advantage has not been evaluated in terms of diagnostic
      accuracy or grading/staging evaluation. AIM: To evaluate whether three separate
      cores of TJLB provide more histological information compared with two or one
      cores. METHODS: Twenty-three patients, who had three separate passes, with each
      core >/=7mm in length using a 19G Tru-cut needle, were evaluated. Each TJLB was
      blindly coded; the pathologist randomly assessed: (a) each core separately
      covering the other two, (b) two cores simultaneously covering the third and (c)
      the three cores together for diagnostic yield, inflammation and fibrosis.
      RESULTS: The mean TJLB length was 32+/-5.5mm. In 12 one-core (52%) and 18 2-core
      (78%) assessments, diagnosis (mainly cirrhosis) was made correctly in each core.
      The within-patient standard deviations for one-core vs two-core assessment were
      similar for grading (0.42 and 0.47, respectively), but higher for staging (0.39
      and 0.15, respectively). Staging was underestimated in assessing one-core and
      less for two cores compared to three cores. CONCLUSION: Three non-fragmented
      cores (each core >/=7mm in length) of TJLB can be considered a minimum
      requirement for histological assessment, giving better reproducibility in
      diagnosis as well as for inflammation and fibrosis.

PMID- 17498251
TI  - The role of psychological factors in the fatigue of primary biliary cirrhosis.
AB  - Fatigue impairs the quality of life of primary biliary cirrhosis (PBC) patients.
      In this study, we explored the psychological factors and coping strategies in
      fatigued PBC patients. Patients participated in a semi-structured interview
      examining thoughts regarding the impact of fatigue and coping strategies. All
      completed the disease-specific quality-of-life tool, PBC-40, the Penn State Worry
      Questionnaire (PSWQ) (degree of habitual worry) and Hospital Anxiety and
      Depression Scale (HADS) (current anxiety and depression). PBC patients were
      allocated into high (>38, n=10) and low-fatigue (<38, n=14) groups. No
      differences were seen between high-fatigue and low-fatigue groups regarding age,
      marital status, employment status, PBC stage, years with diagnosis and years
      experiencing fatigue. High-fatigue participants were significantly more anxious
      (P=0.008), more depressed (P<0.001), and more likely to worry (<0.05). High
      fatigue participants had more frequent thoughts about the impact of fatigue
      (P<0.005) and lower self-efficacy scores (P<0.001). In conclusion, PBC patients
      can experience profound distress associated with fatigue. PBC patients with high
      levels of fatigue seem to be more vulnerable to emotional distress, more likely
      to perceive that their quality of life has been negatively affected and are less
      confident to engage in everyday activities compared with those with low levels of
      fatigue.

PMID- 17498252
TI  - Hepatocyte senescence in end-stage chronic liver disease: a study of cyclin
      dependent kinase inhibitor p21 in liver biopsies as a marker for progression to
      hepatocellular carcinoma.
AB  - BACKGROUND: Histologic markers to predict hepatocellular carcinoma (HCC) include
      small cell change and dysplastic nodules. Hepatocyte senescence is noted in
      chronic liver disease and may or may not be important in progression to HCC. AIM:
      The study was undertaken to compare standard histologic features of chronic liver
      disease as well as markers of senescence and proliferation in two groups of
      biopsies from patients followed for at least a year. METHODS: Standard histologic
      evaluation of necroinflammatory activity, fibrosis, steatosis, and iron,
      internationally accepted criteria of dysplasia, and immunohistochemical markers
      for proliferation and hepatocyte senescence were compared in 47 liver biopsies
      from noncholestatic chronic liver disease patients who subsequently either
      underwent transplant (the Control group, n=19) or had biopsy-proven (HCC group,
      n=28) over a similar time period of 34.9 months (mean) and 42.5 months (mean)
      respectively. RESULTS: Both groups were predominantly men; the MELD score was
      higher, and mean age was less in the Control group (46.9 vs 53.8 years, P=0.01).
      Small cell change was not significantly different in the biopsies between the two
      groups; neither were grade, stage (Ishak scores), nor presence or location of
      iron. Steatosis was more common in the group that subsequently developed HCC
      (P=0.04). The MIB-1 proliferation index was greater in the biopsies from the
      Control group. The senescence marker p21, and the ratio of p21:MIB-1 were not
      statistically different between the two groups. However, a Spearman's rank
      correlation showed a linear correlation of p21/MIB-1 with a greater amount of
      dyplasia in the explant livers of Controls. CONCLUSIONS: These findings suggested
      the Control groups' livers maintained effective removal of cells from the cell
      cycle by overexpression of p21 and, while not 'protected' from significant
      involvement by dysplasia, may have been precluded from development of HCC.

PMID- 17498253
TI  - IL-8 expression by biliary epithelial cells is associated with neutrophilic
      infiltration and reactive bile ductules.
AB  - BACKGROUND/AIMS: Reactive bile ductule is a non-specific feature of various
      hepatobiliary diseases, and is not infrequently accompanied by neutrophilic
      infiltration. Recently, biliary epithelial cells have been shown to secrete
      cytokines and chemokines and to express components of the mucosal immune system
      such as Toll-like receptors. METHODS AND RESULTS: We examined the expression of a
      neutrophil chemo-attractant, interluekin (IL)-8, in bile ductular cells to
      clarify the histogenesis of reactive bile ductules with neutrophilic infiltration
      using human liver tissues (eight cases of chronic viral hepatitis, seven cases of
      liver cirrhosis (LC), seven cases of sepsis, 11 cases of extrahepatic biliary
      obstruction (EBO), three cases of fulminant hepatitis (FH), five cases of primary
      biliary cirrhosis, and three cases of primary sclerosing cholangitis). Human
      neutrophil peptides 1-3 (HNP1-3) were used as markers of neutrophils.
      Immunohistochemically, IL-8 was detected in bile ductules in various diseased
      livers. HNP1-3-positive neutrophils were significantly dense around IL-8-positive
      bile ductules compared with IL-8-negative ductules in septic liver, LC, EBO, and
      FH. Experiments in vitro showed that cultured human biliary epithelial cells
      expressed and secreted IL-8 in response to lipopolysaccharide and also IL-1beta
      and tumour necrosis factor-alpha. CONCLUSIONS: Neutrophilic infiltration around
      reactive bile ductules may be related to the IL-8 expressed in bile ductular
      epithelia, possibly induced by bacterial components and proinflammatory cytokines
      released locally.

PMID- 17498254
TI  - Special stains can distinguish hepatic necrosis with regenerative nodules from
      cirrhosis.
AB  - BACKGROUND: Focal zones of hepatic necrosis alternating with nodular regeneration
      in severe, acute to subacute hepatitis can be difficult to differentiate
      histologically from established cirrhosis, and diagnostic errors can result in
      incorrect patient management. Thus, an easily applicable, well-defined histologic
      method for differentiating these two lesions would be useful. METHODS: We
      examined trichrome (TRI), reticulin (RETIC), Verhoeff's elastic (VE), and orcein
      (ORC) stains on 13 cases of hepatic necrosis with regenerative nodules and 10
      cases of end-stage cirrhosis to evaluate their utility for this problem. RESULTS:
      Zones of recent necrosis in all severe hepatitis cases stained paler blue or
      pink, respectively, with TRI and VE than the established scar in cirrhosis or
      residual normal portal zones/central vein walls. With VE and ORC, elastic fibres
      were not seen in the necrotic zones of severe hepatitis, but were present in all
      cirrhotic livers. RETIC outlined the residual cell plate architecture in necrotic
      areas but had indistinct staining in fibrotic areas. The combination of the
      RETIC, TRI and ORC distinguished hepatic necrosis with regenerative nodules from
      nodules in the scar of established cirrhosis in 100% of the cases examined.
      CONCLUSION: We conclude that this trio of special stains can be helpful adjuncts
      for this diagnostic problem.

PMID- 17498255
TI  - Personnel in cadaveric organ transplant-related hospital units faced with living
      liver donation: an attitudinal study in a Spanish hospital with a cadaveric and
      living liver transplant programme.
AB  - INTRODUCTION: The attitude of health-care personnel is fundamental for the
      procurement of transplant organs, especially in those services that are related
      to transplantation. The objective of this study is to find out the attitude
      towards living liver donation among personnel who work in transplant-related
      services in a hospital with a cadaveric and living organ transplant programme.
      MATERIALS AND METHODS: A random sample was taken and stratified by type of
      service and job category (N=330), in services related to transplantation
      (procurement units, transplant units and follow-up units). Attitude was evaluated
      using a validated psychosocial questionnaire. CONTROL GROUP: a random sample of
      personnel in clinical services that do not have any direct contact with solid
      organ transplantation. Student's t-test and the chi(2) test complemented by a
      logistical regression analysis were applied in the statistical analysis. RESULTS:
      The questionnaire completion rate was 94% (N=309). Only 10% (N=31) of respondents
      are in favour of living liver donation if it is unrelated, but another 67%
      (N=207) are in favour if donation were for a relative. Of the rest, 11% (N=33) do
      not agree with living liver donation and the remaining 12% (N=38) are undecided.
      In the control group, attitude towards living liver donation is favourable in 82%
      (N=344) (P=0.0908). An analysis of the variables that influence attitude shows
      that the following factors are significantly related: (1) age (P=0.037); (2) a
      respondent's belief that he or she may need a transplant in the future (P=0.013);
      and (3) if it were necessary, a willingness to receive a donated living liver
      organ (P=0.000). Of the variables that have the most influence on attitude
      towards living liver donation in the bivariate analysis, there are two variables
      that are statistically significant in the multivariate analysis: (1) age and (2)
      willingness to accept a donated living liver organ from a relative if it were
      needed (OR=14.19). There is also a close relationship between attitude towards
      living liver donation and attitude towards living kidney donation (P=0.000)
      CONCLUSIONS: There is a favourable attitude towards living liver donation among
      personnel in units related to the transplantation and donation process, although
      it is less favourable than expected. Therefore, it will be necessary to increase
      this level of acceptance and to improve information about the matter if we want
      to encourage living liver donation. The youngest workers in these units are those
      who are most in favour, which leads us to believe that there is a hopeful future
      for this type of liver donation that is so necessary given the cadaveric organ
      deficit.

PMID- 17498256
TI  - High aspartate to alanine aminotransferase ratio is an indicator of cirrhosis and
      poor outcome in patients with primary sclerosing cholangitis.
AB  - OBJECTIVES: A liver biopsy is performed mainly to stage primary sclerosing
      cholangitis (PSC). In viral hepatitis, alcoholic liver disease and in primary
      biliary cirrhosis, the ratio of aspartate to alanine aminotransferase (AST/ALT)
      has been proven to be an indicator of liver cirrhosis. We wanted to test whether
      or not an AST/ALT ratio >/=1 is an indicator of cirrhosis also in patients with
      PSC. METHODS: A cohort of 154 patients diagnosed with PSC was studied
      retrospectively. Laboratory tests and the histological stage were scored.
      RESULTS: The mean AST/ALT ratio in the cirrhotic patients at the time of the
      first (n=117) as well as the last (n=72) histological examination was higher
      (1.3+/-0.5 and 1.6+/-0.7, respectively) than in the non-cirrhotic patients (0.7+/
      0.4 and 1.0 +/-0.4, respectively) (P<0.0001 and P=0.0002, respectively). An
      AST/ALT ratio >/=1 was a strong predictor for liver-related death/orthotopic
      liver transplantation and liver-related death, being associated with a double and
      an almost fourfold higher risk, respectively. CONCLUSION: An AST/ALT ratio >/=1
      is significantly associated with the presence of cirrhosis and poor outcome in
      PSC. It may therefore be a valuable non-invasive method for indicating cirrhosis
      in patients with PSC.

PMID- 17498257
TI  - Calcitriol inhibits the growth of MHCC97 heptocellular cell lines by down
      modulating c-met and ERK expressions.
AB  - BACKGROUND: Previous studies have demonstrated that Calcitriol or its analogs has
      an anti-tumour activity. This study was designed to determine the effect and
      mechanism of Calcitriol on MHCC-97 heptocellular cell lines. METHODS: MHCC97 cell
      lines were treated with Calcitriol of 10(-6) approximately 10(-9) M concentration
      and with Calcitriol in lipiodol ultra-fluid (LUF) respectively. The conditions of
      cell proliferation were analyzed by MTT method. The cell apoptosis and cycle were
      analyzed by using a flow cytometer. Hepatocyte growth factor (HGF) concentration
      in the cell supernatant was measured by using ELISA method. C-met and vitamin D
      receptor (VDR) mRNA in cells were determined by using RT-PCR method. VDR and
      ERK(1/2) proteins were determined by using Western Blotting method. RESULTS:
      Calcitriol inhibited the proliferation of MHCC97 cell lines with an accumulation
      of cells in the G(0)/G(1) phase and reduction of cells in S phase. Calcitriol
      dissolved in LUF resulted in a better and longer inhibitive effect on the cell
      lines than Calcitriol alone. MHCC97 cell lines secreted HGF and expressed c-met
      mRNA and ERK(1/2) proteins abundantly. Calcitriol remarkably inhibited the
      expressions of c-met mRNA and ERK(1/2) proteins. CONCLUSION: Calcitriol inhibits
      the growth of MHCC-97 heptocellular cell lines by down modulating c-met and ERK
      expressions.

PMID- 17498258
TI  - The expression of SIRT1 in nonalcoholic fatty liver disease induced by high-fat
      diet in rats.
AB  - OBJECTIVE: SIRT1 is an NAD(+)-dependent deacetylase and its enzymatic activity
      may be regulated by cellular energy. SIRT1 overexpression reduces the level of
      oxygen consumption, which is correlative with nonalcoholic fatty liver disease
      (NAFLD). To elucidate the role of SIRT1 on the development of NAFLD, we
      investigated the expression of SIRT1 in NAFLD induced by high-fat diet in rats
      and the effects of calorie restriction. METHODS: Thirty-one male Wistar rats were
      divided at random into four groups. The rats in the normal control group NC (n=7)
      and in the NAFLD model group HF (n=9) were fed ad libitum with normal chow and
      high-fat diet, respectively, for 3 months, the rats in the calorie restriction
      (CR) group HCR (n=9) were fed with a high-fat diet for 2 months and then 60% CR
      with normal chow for 1 month, and the rats in group CRH (n=6) were firstly fed
      with 60% CR with normal chow for 1 month and then fed a high-fat diet for 2
      months. At the end of the experiment, some parameters and expressions of SIRT1
      were detected. RESULTS: The rats in group HF displayed NAFLD. Compared with group
      NC, the expression of SIRT1 protein was significantly decreased (P<0.01).
      However, the lower body weight and visceral fat mass of rats in group HCR were
      showed. Compared with group HF, CR increased the expression of SIRT1 in liver
      significantly (P<0.01). Consequently, the ultramicropathology changes of NAFLD
      prominently improved in this group. Meanwhile, the rats in group CRH displayed
      higher expression of SIRT1 protein and very gentle pathology changes of NAFLD.
      CONCLUSION: The expression of SIRT1 is reduced significantly in NAFLD induced by
      high-fat diet in rats. CR increase-SIRT1 protein expression may be an important
      mechanism by which CR improves NAFLD.

PMID- 17498259
TI  - Hepatocellular carcinoma producing a granulocyte colony-stimulating factor:
      report of a resected case with a literature review.
AB  - A complete resection of a hepatocellular carcinoma (HCC) producing the
      granulocyte colony-stimulating factor (G-CSF) was performed and is reported here.
      The patient had a few general symptoms and complications, such as the
      paraneoplastic syndrome. He had marked granulocytosis, and his serum levels of G
      CSF and interleukin-6 were elevated. The pathological findings of the resected
      specimen revealed poorly differentiated HCC with sarcomatous change and showed,
      immunohistochemically, staining of G-CSF. Only a few cases of G-CSF-producing HCC
      have been reported, and they resulted in rapid tumour growth and poor prognosis.
      The case presented here may be the first complete resection ever performed, but
      the patient's prognosis was similar to that observed in typical cases.

PMID- 17498260
TI  - Profound suppression of chronic hepatitis C following superinfection with
      hepatitis B virus.
AB  - BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) share similar
      transmission routes; thus, coinfection is frequent. The consequences of acute HBV
      infection in patients with chronic hepatitis C are unknown. METHODS: We describe
      a 47-year-old male with chronic hepatitis C who acquired HBV and then
      spontaneously and apparently completely cleared HCV but developed chronic
      hepatitis B. Five serum samples collected over 14 months and lymphoid cells
      obtained after acquiring HBV were tested for HCV and HBV by both standard assays
      and ultra-sensitive polymerase chain reaction/nucleic acid hybridization
      (PCR/NAH) (sensitivity approximately 2 IU/ml). RESULTS: After superinfection with
      HBV, HBV surface antigen-positive chronic hepatitis developed with readily
      detectable HBV DNA. All sera collected after acquisition of HBV, which tested
      negative for HCV RNA by standard laboratory assay, were positive for HCV genomes
      when analysed by PCR/NAH. Peripheral lymphoid cells carried HBV DNA and
      covalently closed circular DNA, but were negative for HCV. CONCLUSIONS: This is
      the first reported case of profound suppression of chronic hepatitis C after
      superinfection with HBV and establishment of chronic hepatitis B. It is
      hypothesized that HBV infection precipitated generalized and/or virus-specific
      cellular immune responses that profoundly suppressed HCV replication and yet
      failed to inhibit progression to chronic hepatitis B.

PMID- 17498261
TI  - Successful interferon treatment in a patient chronically infected with hepatitis
      B virus carrying unusual S- (and P-) mutants in the presence of anti-HBs
      antibodies.
AB  - BACKGROUND: Hepatitis B virus (HBV) immune escape mutants with point mutations
      within the S gene may arise during the natural course of HBV infection, due to a
      positive selection pressure exerted by the host immune response. Mutations within
      the immunodominant B and T cell epitopes of hepatitis B surface antigen (HBsAg)
      allow the resulting S-mutants to propagate even in the presence of neutralizing
      anti-HBs antibodies and the HBV-specific T-cell immune response. AIM: To study
      the antiviral effect of Pegylated-interferon (Peg-IFN) in a patient with chronic
      hepatitis B carrying unusual S-(and P-) mutants in the presence of anti-HBs
      antibodies. PATIENTS, METHODS AND RESULTS: We report on a 43-year-old male
      chronically infected with a genotype A HBV strain, with cocirculation of both
      HBsAg and anti-HBs antibodies, who received treatment with 120 mug of Peg-IFN for
      24 weeks. HBeAg seroconversion and clearance of both HBV DNA by polymerase chain
      reaction and HBsAg were successfully achieved. Improved histology was observed in
      a biopsy performed 44 weeks after Peg-IFN therapy was completed. It seems
      plausible that the ascribed genotype A could have contributed to the effective
      response to Peg-IFN, even though the treatment was provided only throughout a 24
      week period. CONCLUSION: To our knowledge, this is the first report regarding the
      successful result obtained by using Peg-IFN as a treatment for a chronically HBV
      infected patient carrying HBsAg immune escape mutants.

PMID- 17498262
TI  - Towards an evidence-based guideline for counselling of chronic hepatitis B virus
      infected patients.

PMID- 17498264
TI  - Allorecognition and the alloresponse: clinical implications.
AB  - The artificial transfer of tissues or cells between genetically diverse
      individuals elicits an immune response that is adaptive and specific. This
      response is orchestrated by T lymphocytes that are recognizing, amongst others,
      major histocompatibility complex (MHC) molecules expressed on the surface of the
      transferred cells. Three pathways of recognition are described: direct, indirect
      and semi-direct. The sets of antigens that are recognized in this setting are
      also discussed, namely, MHC protein products, the MHC class I-related chain (MIC)
      system, minor histocompatibility antigens and natural killer cell receptor
      ligands. The end product of the effector responses are hyperacute, acute and
      chronic rejection. Special circumstances surround the situation of pregnancy and
      bone marrow transplantation because in the latter, the transferred cells are the
      ones originating the immune response, not the host. As the understanding of these
      processes improves, the ability to generate clinically viable immunotherapies
      will increase.

PMID- 17498265
TI  - Association and interaction of the TNF-alpha gene with other pro- and anti
      inflammatory cytokine genes and HLA genes in patients with type 1 diabetes from
      North India.
AB  - Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where major
      histocompatibility complex (MHC) genes and the insulin-linked polymorphic region
      have been shown to play major roles. We report here an integrated effect of tumor
      necrosis factor (TNF) alpha with other cytokine genes. The TNF-alpha-308 GA and
      AA (high secretor) polymorphisms were significantly increased in the patients
      with T1D (n = 235) [P < 7 x 10(-6), odds ratio (OR) = 3.04, 95% confidence
      interval (CI) = 1.8-5.3] compared with the controls (n= 128). The variants of
      interferon-gamma (IFN-gamma) (A(+874)T), interleukin (IL)-6 (G(-174)C), IL-10 (A(
      1082)G, T(-819)C, C(-592)A) and transforming growth factor (TGF) beta1
      (T(cdn10)C, G(cdn25)C) did not show a significant difference between patients and
      controls. However, simultaneous presence of TNF-alpha-308 GA+AA along with both
      high and low secretor genotypes of IFN-gamma (P < 0.003) was significantly
      increased in patients. Simultaneous presence of TNF-alpha-308 GA + AA along with
      high secretor genotypes of IL-6 (P < 0.0001, OR = 2.61, 95% CI = 1.5-4.56), IL-10
      (P < 0.0001, OR = 4.26, 95% CI = 1.9-10.1) and TGF-beta1 (P < 0.00004, OR = 2.8,
      95% CI = 1.6-4.86) was also significantly increased in patients with T1D. Low
      secretor genotype of TNF-alpha-308 GG along with low secretor genotypes of IFN
      gamma (P < 0.001, OR = 0.465, 95% CI = 0.28-0.77), high secretor genotypes of IL
      6 (P < 0.000004, OR = 0.76, 95% CI = 0.227-0.621) and TGF-beta1 (P < 0.000006, OR
      = 0.336, 95% CI = 0.198-0.568) was protective. The TNF-alpha-308 G allele was in
      linkage disequilibrium (LD) with the human leukocyte antigen (HLA)-B*0801
      DRB1*0301 haplotype, while TNF-alpha-308 A allele was in LD with the HLA-B*5001
      DRB1*0301 and B*5801-DRB1*0301 haplotypes, suggesting that the effect of TNF
      alpha -308 A allele is not because of its being in LD with any HLA alleles, but
      because of its functional role and its integrated effect with other cytokines.

PMID- 17498266
TI  - KIR genes polymorphism in Argentinean Caucasoid and Amerindian populations.
AB  - In natural killer cells, killer immunoglobulin-like receptors (KIRs) loci code
      for either inhibitory or activating receptors, and according to the number of
      genes present in each individual, it is possible to identify a high rate of
      polymorphism in the populations. We performed KIR typing by polymerase chain
      reaction-sequence-specific oligonucleotide probing in 402 Argentinean Caucasoid
      and in two Amerindian populations (101 Wichis and 54 Chiriguanos) from the North
      of Argentina. KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 were always present, whereas
      the frequencies of KIR2DL1, KIR2DL3, KIR2DS4, KIR3DL1 and KIR2DP1 ranged between
      84% and 96%. The frequencies of KIR2DS2, KIR2DL2, KIR2DL5, KIR2DS5, KIR2DS1 and
      KIR3DS1 ranged between 41% and 62%. The KIR2DS3 with a frequency of 29% in
      Argentinean Caucasoid population was present at a very low frequency in
      Amerindian populations. Haplotype segregation studies performed in 10 Wichi
      families showed the presence of only three haplotypes: A, B5 and B1. The
      Amerindian populations showed several similarities to Asian but not to Caucasoid
      populations with regard to the frequency of KIR2DS3, full-length KIR2DS4 gene and
      KIR2DL4 alleles.

PMID- 17498267
TI  - No association in frequency of KIR receptors in patients with rheumatoid
      arthritis from Northern Ireland.
AB  - The frequency of inhibiting and activating killer cell immunoglobulin-like
      receptors was similar in 331 patients with rheumatoid arthritis and in 354
      controls. Patients and controls came from a relatively homogeneous Caucasian
      population from Northern Ireland, thus limiting population stratification.
      Furthermore, no differences were found when the patients were sub-divided
      according to gender or shared epitope and when the presence of the human
      leucocyte antigen ligand was taken into account.

PMID- 17498268
TI  - Allograft inflammatory factor-1 and tumor necrosis factor single nucleotide
      polymorphisms in systemic sclerosis.
AB  - Tumor necrosis factor (TNF) alleles have been associated with systemic sclerosis
      (SSc); however, these alleles may be in linkage with other genes. Allograft
      inflammatory factor-1 (AIF-1) is a newly identified gene on the short arm of
      chromosome 6 in the class III region of the human leukocyte antigen. It appears
      to be involved in inflammation and was originally identified in rat cardiac
      allografts undergoing rejection. AIF-1 has several sequence variations (single
      nucleotide polymorphisms, SNPs), three of which result in nonsynonymous changes
      in amino acid coding. We analyzed the linkage of five TNFA and five AIF-1 SNPs by
      polymerase chain reaction in 239 Caucasian individuals. The TNFA-1031T/T genotype
      was found to be associated with SSc (P < 0.0001) and both the DcSSc (diffuse
      subset of SSc) and the LcSSc (limited subset of SSc) subsets (P= 0.0004 and P=
      0.0009, respectively) and the TNFA-237G/G genotype was found to be associated
      with all SSc (P= 0.0003) and with the DcSSc and LcSSc subsets (P= 0.01 and P=
      0.005, respectively). Furthermore, the TNFA-857C/T genotype was associated with
      LcSSc (P= 0.0003) and TNFA-307A/A genotype associated with DcSSc (P= 0.028). In
      AIF-1, RS2269475 exon 4A allele, which generates a nonsynonymous change
      (tryptophan to arginine), was significantly associated in patients with SSc (P=
      0.0009) and was associated with those patients who had DcSSc (P= 0.002). A strong
      linkage disequilibrium was observed between the AIF-1 alleles, A allele of
      RS2269475 and the A allele of RS4711274 (P < 0.0001), and linkage was observed
      between AIF-1 and TNFA alleles. Here, we report a novel and significant
      association of a nonsynonymous change within the AIF-1 with SSc and identified
      the linkage with TNFA alleles within 50 kb of this gene. Our study lends support
      that TNFA may be an important inflammatory modulator in SSc and may play a
      significant role with AIF-1 in disease pathogenesis.

PMID- 17498269
TI  - HLA alleles as predisposal factors for postmenopausal osteoporosis in a Greek
      population.
AB  - It is well established that genetic factors play an important role in the
      pathogenesis of osteoporosis, a common condition characterized by reduced bone
      mass and increased fracture risk. The major histocompatibility complex in humans,
      known as human leukocyte antigen (HLA) region, is the most polymorphic human
      genetic system and it is known as a cluster of genetic markers, associated with
      several diseases. In order to evaluate the contribution of HLA alleles in bone
      mass loss, polymorphisms in the HLA class I (-A, -B and -Cw) and class II (-DR
      and -DQ) antigens were studied in 126 postmenopausal women of Greek origin. It
      was found that HLA-B7 (P= 0.069), -DR15 (P= 0.019) and -DQ6 (P= 0.026) were
      associated with a lower bone mineral density measured at the forearm. This study
      shows a significant association between HLA alleles and bone mass loss in the
      population studied.

PMID- 17498270
TI  - Enrichment of individual KIR2DL4 sequences from genomic DNA using long-template
      PCR and allele-specific hybridization to magnetic bead-bound oligonucleotide
      probes.
AB  - DNA enrichment by allele-specific hybridization (DEASH) was used as a means to
      isolate individual alleles of the killer cell immunoglobulin-like receptor
      (KIR2DL4) gene from heterozygous genomic DNA. Using long-template polymerase
      chain reaction (LT-PCR), the complete KIR2DL4 gene was amplified from a cell line
      that had previously been characterized for its KIR gene content by PCR using
      sequence-specific primers (PCR-SSP). The whole gene amplicons were sequenced and
      we identified two heterozygous positions in accordance with the predictions of
      the PCR-SSP. The amplicons were then hybridized to allele-specific, biotinylated
      oligonucleotide probes and through binding to streptavidin-coated beads, the
      targeted alleles were enriched. A second PCR amplified only the exonic regions of
      the enriched allele, and these were then sequenced in full. We show DEASH to be
      capable of enriching single alleles from a heterozygous PCR product, and through
      sequencing the enriched DNA, we are able to produce complete coding sequences of
      the KIR2DL4 alleles in accordance with the typing predicted by PCR-SSP.

PMID- 17498271
TI  - Nomenclature of prominin-1 (CD133) splice variants - an update.
AB  - Prominin-1 (CD133), a pentaspan membrane glycoprotein that constitutes an
      important cell surface marker of various, either normal or cancerous, stem cell
      populations is widely used to isolate or characterize such cells in different
      systems. Occurring throughout the metazoan evolution with a remarkably conserved
      genomic organization, it may be expressed as different splice variants with
      distinctive characteristics. A rational nomenclature has been proposed earlier
      for their consistent designation across species. Although generally accepted, it
      seems to be misunderstood in view of the recent report of novel prominin-1
      complementary DNAs in rhesus monkey and humans with improper naming. As this may
      lead to confusion, we have reexamined the genomic organization of prominin-1 in
      various primates to provide an update that should further clarify the rationale
      of the nomenclature for prominin-1 gene products. This report comprises (i) the
      determination of the genomic organization of prominin-1 gene in two non-human
      primates, i.e. Macaca mulatta and Pan troglodytes, commonly used in research,
      (ii) the mapping of a new exon that creates an alternative cytoplasmic C-terminal
      end of prominin-1, (iii) the identification of various potential PDZ-binding
      domains generated by alternative cytoplasmic C-terminal tails, suggesting that
      different prominin-1 splice variants might interact with distinct protein
      partners, and (iv) a summing up of the different prominin-1 splice variants.

PMID- 17498272
TI  - Identification of three novel alleles of HLA-DRB1 and HLA-A in the Brazilian
      population.
AB  - Two human leukocyte antigen (HLA)-DRB1 (HLA-DRB1*1376 and -DRB1*1465) and one HLA
      A (HLA-A*2471) novel alleles have been identified in individuals from the
      Brazilian Bone Marrow Donor Registry. DNA sequencing of exon 2 for HLA-DRB1
      alleles showed two and five nucleotide substitutions in -DRB1*1376 and 
      DRB1*1465, compared with closely related alleles, respectively. These
      substitutions result in a change of amino acid residues in HLA-DRB1*1376 at
      position 74 (Arg --> Glu) and in -DRB*1465 at positions 47 (Tyr --> Phe), 57 (Asp
      --> Ser) and 74 (Glu --> Ala). On the other hand, sequence analysis of exons 2
      and 3 for HLA-A*2471 showed a single substitution, leading to a single amino acid
      change at position 151 (His --> Arg). These three novel alleles may have
      originated from other HLA alleles by gene conversion. However, it is also
      possible that HLA-A*2471 has evolved from one of the alleles of the HLA-A*2402
      group through a point mutation.

PMID- 17498273
TI  - HLA-A*1129, a new allele identified in a cord blood donor.
AB  - The new allele HLA-A*1129 showed one nucleotide difference form A*110101 at codon
      172 (CTG>CAG).

PMID- 17498274
TI  - Identification of a novel HLA-A*26 allele, HLA-A*2632, by sequence-based typing
      in the Korean population.
AB  - HLA-A*2632 shows three nucleotides difference with HLA-A*260101 and HLA-A*2624 in
      exon 3 at codon 95 (ATC--> ATG) and codon 97 (AGG --> GTG), resulting in two
      amino acids change from Ile to Met (I95M) and Arg to Val (R97V).

PMID- 17498275
TI  - HLA-A*2634, a new allele identified by sequence-based typing in the Korean
      population.
AB  - A new HLA-A*2634 allele differs from A*260101 by a change from C to T at the
      nucleotide 559 of exon 3, with a coding change R163W.

PMID- 17498276
TI  - Identification of the uncommon allele HLA-A*7403 in a Caucasian renal transplant
      cadaveric donor: extension of the exon 4 sequence.
AB  - This report describes the unknown exon 4 sequence of the rare A*7403 allele,
      identified in a Caucasian renal transplant cadaveric donor from Italy. This
      sequence is identical to that of the only known A*7401 exon 4, and this result
      allowed us to confirm the hypothesis of the generation of A*7403 allele from the
      ancestor A*7402 by point mutation in exon 2.

PMID- 17498277
TI  - Identification of a novel HLA-B allele HLA-B*4070 in a Chinese donor.
AB  - Identification of a novel human leukocyte antigen-B allele HLA-B*4070.

PMID- 17498278
TI  - HLA-B*9523 increases the extremely high B*15-group polymorphism.
AB  - HLA-B*9523 differs from B*1591 and B*1503 in point nucleotide mutations at codon
      167 (TCG --> TGG) and 152 (GAG --> GTG), respectively.

PMID- 17498279
TI  - Identification of a novel allele HLA-DRB1*0114 in two Chinese marrow donors by
      sequence-based typing.
AB  - A novel human leukocyte antigen (HLA) class II, DRB1*0114, has been identified in
      routine typing of bone marrow donors for the Chinese Marrow Donor Registry in
      Shaanxi, China. The DRB1*0114 allele differs from DRB1*0101 by three nucleotide
      substitutions, causing two amino acid changes.

PMID- 17498280
TI  - Nomenclature for factors of the HLA system, update January 2007.

PMID- 17498281
TI  - Study protocol: a randomised controlled trial of multiple and single dose
      activated charcoal for acute self-poisoning.
AB  - BACKGROUND: The case fatality for intentional self-poisoning in rural Asia is 10
      30 times higher than in the West, mostly due to the use of highly toxic poisons.
      Activated charcoal is a widely available intervention that may - if given early -
      bind to poisons in the stomach and prevent their absorption. Current guidelines
      recommend giving a single dose of charcoal (SDAC) if patients arrive within an
      hour of ingestion. Multiple doses (MDAC) may increase poison elimination at a
      later time by interrupting any enterohepatic or enterovascular circulations. The
      effectiveness of SDAC or MDAC is unknown. Since most patients present to hospital
      after one hour, we considered MDAC to have a higher likelihood of clinical
      benefit and set up a study to compare MDAC with no charcoal. A third arm of SDAC
      was added to help determine whether any benefit noted from MDAC resulted from the
      first dose or all doses. METHODS/DESIGN: We set up a randomised controlled trial
      assessing the effectiveness of superactivated charcoal in unselected adult self
      poisoning patients admitted to the adult medical wards of three Sri Lankan
      secondary hospitals. Patients were randomised to standard treatment or standard
      treatment plus either a single 50 g dose of superactivated charcoal dissolved in
      300 ml of water or six doses every four hours. All patients with a history of
      poison ingestion were approached concerning the study and written informed
      consent taken from each patient, or their relative (for unconscious patients or
      those <16 yrs), recruited to the study. The exclusion criteria were: age under 14
      yrs; prior treatment with activated charcoal during this poisoning episode;
      pregnancy; ingestion of a corrosive or hydrocarbon; requirement for oral
      medication; inability of the medical staff to intubate the patient with a Glasgow
      Coma Score <13; presentation >72 hrs post-ingestion, and previous recruitment.
      The primary outcome was in-hospital mortality; secondary outcomes included the
      occurrence of serious complications (need for intubation, time requiring assisted
      ventilation, fits, cardiac dysrhythmias). Analysis will be on an intention-to
      treat basis; the effects of reported time to treatment after poisoning and status
      on admission will also be assessed. DISCUSSION: This trial will provide important
      information on the effectiveness of both single and multiple dose activated
      charcoal in the forms of poisoning commonly seen in rural Asia. If charcoal is
      found to be effective, it should be possible to make it widely available across
      rural Asia in an affordable formulation. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN02920054.

PMID- 17498282
TI  - Hypoplastic left heart syndrome.
AB  - Hypoplastic left heart syndrome (HLHS) refers to the abnormal development of the
      left-sided cardiac structures, resulting in obstruction to blood flow from the
      left ventricular outflow tract. In addition, the syndrome includes
      underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral
      atresia or stenosis. HLHS has been reported to occur in approximately 0.016 to
      0.036% of all live births. Newborn infants with the condition generally are born
      at full term and initially appear healthy. As the arterial duct closes, the
      systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and
      shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected.
      The second heart sound is loud and single because of aortic atresia. Often the
      liver is enlarged secondary to congestive heart failure. The embryologic cause of
      the disease, as in the case of most congenital cardiac defects, is not fully
      known. The most useful diagnostic modality is the echocardiogram. The syndrome
      can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation.
      Differential diagnosis includes other left-sided obstructive lesions where the
      systemic circulation is dependent on ductal flow (critical aortic stenosis,
      coarctation of the aorta, interrupted aortic arch). Children with the syndrome
      require surgery as neonates, as they have duct-dependent systemic circulation.
      Currently, there are two major modalities, primary cardiac transplantation or a
      series of staged functionally univentricular palliations. The treatment chosen is
      dependent on the preference of the institution, its experience, and also
      preference. Although survival following initial surgical intervention has
      improved significantly over the last 20 years, significant mortality and
      morbidity are present for both surgical strategies. As a result pediatric
      cardiologists continue to be challenged by discussions with families regarding
      initial decision relative to treatment, and long-term prognosis as information on
      long-term survival and quality of life for those born with the syndrome is
      limited.

PMID- 17498283
TI  - Oesophageal atresia.
AB  - Oesophageal atresia (OA) encompasses a group of congenital anomalies comprising
      of an interruption of the continuity of the oesophagus with or without a
      persistent communication with the trachea. In 86% of cases there is a distal
      tracheooesophageal fistula, in 7% there is no fistulous connection, while in 4%
      there is a tracheooesophageal fistula without atresia. OA occurs in 1 in 2500
      live births. Infants with OA are unable to swallow saliva and are noted to have
      excessive salivation requiring repeated suctioning. Associated anomalies occur in
      50% of cases, the majority involving one or more of the VACTERL association
      (vertebral, anorectal, cardiac, tracheooesophageal, renal and limb defects). The
      aetiology is largely unknown and is likely to be multifactorial, however, various
      clues have been uncovered in animal experiments particularly defects in the
      expression of the gene Sonic hedgehog (Shh). The vast majority of cases are
      sporadic and the recurrence risk for siblings is 1%. The diagnosis may be
      suspected prenatally by a small or absent stomach bubble on antenatal ultrasound
      scan at around 18 weeks gestation. The likelihood of an atresia is increased by
      the presence of polyhydramnios. A nasogastric tube should be passed at birth in
      all infants born to a mother with polyhydramnios as well as to infants who are
      excessively mucusy soon after delivery to establish or refute the diagnosis. In
      OA the tube will not progress beyond 10 cm from the mouth (confirmation is by
      plain X-ray of the chest and abdomen). Definitive management comprises
      disconnection of the tracheooesophageal fistula, closure of the tracheal defect
      and primary anastomosis of the oesophagus. Where there is a "long gap" between
      the ends of the oesophagus, delayed primary repair should be attempted. Only very
      rarely will an oesophageal replacement be required. Survival is directly related
      to birth weight and to the presence of a major cardiac defect. Infants weighing
      over 1500 g and having no major cardiac problem should have a near 100% survival,
      while the presence of one of the risk factors reduces survival to 80% and further
      to 30-50% in the presence of both risk factors.

PMID- 17498284
TI  - Widespread positive selection in the photosynthetic Rubisco enzyme.
AB  - BACKGROUND: Rubisco enzyme catalyzes the first step in net photosynthetic CO2
      assimilation and photorespiratory carbon oxidation and is responsible for almost
      all carbon fixation on Earth. The large subunit of Rubisco is encoded by the
      chloroplast rbcL gene, which is widely used for reconstruction of plant
      phylogenies due to its conservative nature. Plant systematicists have mainly used
      rbcL paying little attention to its function, and the question whether it evolves
      under Darwinian selection has received little attention. The purpose of our study
      was to evaluate how common is positive selection in Rubisco among the phototrophs
      and where in the Rubisco structure does positive selection occur. RESULTS: We
      searched for positive selection in rbcL sequences from over 3000 species
      representing all lineages of green plants and some lineages of other phototrophs,
      such as brown and red algae, diatoms, euglenids and cyanobacteria. Our molecular
      phylogenetic analysis found the presence of positive selection in rbcL of most
      analyzed land plants, but not in algae and cyanobacteria. The mapping of the
      positively selected residues on the Rubisco tertiary structure revealed that they
      are located in regions important for dimer-dimer, intradimer, large subunit-small
      subunit and Rubisco-Rubisco activase interactions, and that some of the
      positively selected residues are close to the active site. CONCLUSION: Our
      results demonstrate that despite its conservative nature, Rubisco evolves under
      positive selection in most lineages of land plants, and after billions of years
      of evolution Darwinian selection still fine-tunes its performance. Widespread
      positive selection in rbcL has to be taken into account when this gene is used
      for phylogenetic reconstructions.

PMID- 17498285
TI  - Trick or treat?
AB  - The purpose of this article is to draw attention to current transgressions in
      scientific writing and to promote commitment to ethical standards and good
      science. All participants of any research project, particularly under
      interdiciplinary team approach, should not only play an active role on the
      management and carrying out of their study but also ensure that their study is
      not fraudulent. Manuscript fabrication, data and/or figure manupilation, piracy
      (plagiarism), sloppy research, and transgressions in authorship are reasons for
      loss of scientific value and records, retraction of articles, and application of
      a variety of sanctions.

PMID- 17498286
TI  - Sirolimus inhibits key events of restenosis in vitro/ex vivo: evaluation of the
      clinical relevance of the data by SI/MPL- and SI/DES-ratios.
AB  - BACKGROUND: Sirolimus (SRL, Rapamycin) has been used successfully to inhibit
      restenosis both in drug eluting stents (DES) and after systemic application. The
      current study reports on the effects of SRL in various human in vitro/ex vivo
      models and evaluates the theoretical clinical relevance of the data by SI/MPL-
      and SI/DES-ratio's. METHODS: Definition of the SI/MPL-ratio: relation between
      significant inhibitory effects in vitro/ex vivo and the maximal plasma level
      after systemic administration in vivo (6.4 ng/ml for SRL). Definition of the
      SI/DES-ratio: relation between significant inhibitory effects in vitro/ex vivo
      and the drug concentration in DES (7.5 mg/ml in the ISAR drug-eluting stent
      platform). Part I of the study investigated in cytoflow studies the effect of SRL
      (0.01-1000 ng/ml) on TNF-alpha induced expression of intercellular adhesion
      molecule 1 (ICAM-1) in human coronary endothelial cells (HCAEC) and human
      coronary smooth muscle cells (HCMSMC). Part II of the study analysed the effect
      of SRL (0.01-1000 ng/ml) on cell migration of HCMSMC. In part III, IV, and V of
      the study ex vivo angioplasty (9 bar) was carried out in a human organ culture
      model (HOC-model). SRL (50 ng/ml) was added for a period of 21 days, after 21 and
      56 days cell proliferation, apoptosis, and neointimal hyperplasia was studied.
      RESULTS: Expression of ICAM-1 was significantly inhibited both in HCAEC (SRL > or
      = 0.01 ng/ml) and HCMSMC (SRL > or = 10 ng/ml). SRL in concentrations > or = 0.1
      ng/ml significantly inhibited migration of HCMSMC. Cell proliferation and
      neointimal hyperplasia was inhibited at day 21 and day 56, significance (p <
      0.01) was achieved for the inhibitory effect on cell proliferation in the media
      at day 21. The number of apoptotic cells was always below 1%. CONCLUSION: SI/MPL
      ratio's < or = 1 (ICAM-1 expression, cell migration) characterize inhibitory
      effects of SRL that can be theoretically expected both after systemic and local
      high dose administration, a SI/MPL-ratio of 7.81 (cell proliferation) represents
      an effect that was achieved with drug concentrations 7.81-times the MPL. SI/DES
      ratio's between 10-6 and 10-8 indicate that the described inhibitory effects of
      SRL have been detected with micro to nano parts of the SRL concentration in the
      ISAR drug-eluting stent platform. Drug concentrations in DES will be a central
      issue in the future.

PMID- 17498287
TI  - Revealing signaling pathway deregulation by using gene expression signatures and
      regulatory motif analysis.
AB  - Gene expression signatures consisting of tens to hundreds of genes have been
      found to be informative for different biological states. Recently, many
      computational methods have been proposed for biological interpretation of such
      signatures. However, there is a lack of methods for identifying cell signaling
      pathways whose deregulation results in an observed expression signature. We
      present a strategy for identifying such signaling pathways and evaluate the
      strategy using six human and mouse gene expression signatures.

PMID- 17498288
TI  - Evolution of pigment synthesis pathways by gene and genome duplication in fish.
AB  - BACKGROUND: Coloration and color patterning belong to the most diverse phenotypic
      traits in animals. Particularly, teleost fishes possess more pigment cell types
      than any other group of vertebrates. As the result of an ancient fish-specific
      genome duplication (FSGD), teleost genomes might contain more copies of genes
      involved in pigment cell development than tetrapods. No systematic genomic
      inventory allowing to test this hypothesis has been drawn up so far for
      pigmentation genes in fish, and almost nothing is known about the evolution of
      these genes in different fish lineages. RESULTS: Using a comparative genomic
      approach including phylogenetic reconstructions and synteny analyses, we have
      studied two major pigment synthesis pathways in teleost fish, the melanin and the
      pteridine pathways, with respect to different types of gene duplication. Genes
      encoding three of the four enzymes involved in the synthesis of melanin from
      tyrosine have been retained as duplicates after the FSGD. In the pteridine
      pathway, two cases of duplicated genes originating from the FSGD as well as
      several lineage-specific gene duplications were observed. In both pathways, genes
      encoding the rate-limiting enzymes, tyrosinase and GTP-cyclohydrolase I (GchI),
      have additional paralogs in teleosts compared to tetrapods, which have been
      generated by different modes of duplication. We have also observed a previously
      unrecognized diversity of gchI genes in vertebrates. In addition, we have found
      evidence for divergent resolution of duplicated pigmentation genes, i.e.,
      differential gene loss in divergent teleost lineages, particularly in the
      tyrosinase gene family. CONCLUSION: Mainly due to the FSGD, teleost fishes
      apparently have a greater repertoire of pigment synthesis genes than any other
      vertebrate group. Our results support an important role of the FSGD and other
      types of duplication in the evolution of pigmentation in fish.

PMID- 17498289
TI  - Comparison of short-term outcomes between laparoscopically-assisted vs.
      transverse-incision open right hemicolectomy for right-sided colon cancer: a
      retrospective study.
AB  - BACKGROUND: Laparoscopically-assisted right hemicolectomy (LRH) is an acceptable
      alternative to open surgery for right-sided colon cancer which offers patients
      less pain and faster recovery. However, special equipment and substantial
      surgical experience are required. The aim of the study is to compare the short
      term surgical outcomes of LRH and open right hemicolectomy through right
      transverse skin crease incision (ORHT) for right-sided colon cancer. PATIENTS AND
      METHODS: This retrospective study included 33 patients with right-sided colon
      cancer who underwent elective right hemicolectomy by laparoscopic or open
      approaches through right transverse skin crease incision between March 2004 and
      September 2006 at the Department of Surgery, Faculty of Medicine Siriraj
      Hospital. Operative details, postoperative requirement of narcotics, recovery of
      bowel function, and oncological parameters were analyzed. RESULTS: Thirteen
      patients underwent LRH and 20 patients underwent ORHT. Both approaches achieved
      adequate oncological resection of the tumor. The laparoscopic group were
      characterized by shorter average incision lengths (7.7 vs 10.3 cm; p < 0.001),
      but longer average operating times (208 vs 105 min; p < 0.001). There was no
      significant difference in the time to first bowel movement, time to defecation,
      and time to resumption of normal diet between both groups (59 vs 64 hr; p = 0.64,
      3.2 vs 3.7 d; p = 0.25 and 3.9 vs 4.3 d; p = 0.39). There was no statistically
      significant difference in the time to discontinuation of intravenous nacrotics
      and the length of hospital stay (1.0 vs 1.4 d; p = 0.25 and 6.2 vs 7.1 d; p =
      0.3). CONCLUSION: LRH and ORHT for right-sided colon cancer resulted in the same
      short-term surgical outcomes including postoperative bowel function, narcotics
      consumption and length of hospital stay. However, LRH required a significantly
      longer operating time.

PMID- 17498290
TI  - Accelerated cellular senescence in degenerate intervertebral discs: a possible
      role in the pathogenesis of intervertebral disc degeneration.
AB  - Current evidence implicates intervertebral disc degeneration as a major cause of
      low back pain, although its pathogenesis is poorly understood. Numerous
      characteristic features of disc degeneration mimic those seen during ageing but
      appear to occur at an accelerated rate. We hypothesised that this is due to
      accelerated cellular senescence, which causes fundamental changes in the ability
      of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to
      IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue
      were assessed for mean telomere length, senescence-associated beta-galactosidase
      (SA-beta-gal), and replicative potential. Expression of P16INK4A (increased in
      cellular senescence) was also investigated in IVD tissue by means of
      immunohistochemistry. RNA from tissue and cultured cells was used for real-time
      polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a
      disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean
      telomere length decreased with age in cells from non-degenerate tissue and also
      decreased with progressive stages of degeneration. In non-degenerate discs, there
      was an age-related increase in cellular expression of P16INK4A. Cells from
      degenerate discs (even from young patients) exhibited increased expression of
      P16INK4A, increased SA-beta-gal staining, and a decrease in replicative
      potential. Importantly, there was a positive correlation between P16INK4A and
      matrix-degrading enzyme gene expression. Our findings indicate that disc cell
      senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore,
      the senescent phenotype is associated with increased catabolism, implicating
      cellular senescence in the pathogenesis of IVD degeneration.

PMID- 17498291
TI  - Genome-wide identification of novel expression signatures reveal distinct
      patterns and prevalence of binding motifs for p53, nuclear factor-kappaB and
      other signal transcription factors in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Differentially expressed gene profiles have previously been observed
      among pathologically defined cancers by microarray technologies, including head
      and neck squamous cell carcinomas (HNSCCs). However, the molecular expression
      signatures and transcriptional regulatory controls that underlie the
      heterogeneity in HNSCCs are not well defined. RESULTS: Genome-wide cDNA
      microarray profiling of ten HNSCC cell lines revealed novel gene expression
      signatures that distinguished cancer cell subsets associated with p53 status.
      Three major clusters of over-expressed genes (A to C) were defined through
      hierarchical clustering, Gene Ontology, and statistical modeling. The promoters
      of genes in these clusters exhibited different patterns and prevalence of
      transcription factor binding sites for p53, nuclear factor-kappaB (NF-kappaB),
      activator protein (AP)-1, signal transducer and activator of transcription
      (STAT)3 and early growth response (EGR)1, as compared with the frequency in
      vertebrate promoters. Cluster A genes involved in chromatin structure and
      function exhibited enrichment for p53 and decreased AP-1 binding sites, whereas
      clusters B and C, containing cytokine and antiapoptotic genes, exhibited a
      significant increase in prevalence of NF-kappaB binding sites. An increase in
      STAT3 and EGR1 binding sites was distributed among the over-expressed clusters.
      Novel regulatory modules containing p53 or NF-kappaB concomitant with other
      transcription factor binding motifs were identified, and experimental data
      supported the predicted transcriptional regulation and binding activity.
      CONCLUSION: The transcription factors p53, NF-kappaB, and AP-1 may be important
      determinants of the heterogeneous pattern of gene expression, whereas STAT3 and
      EGR1 may broadly enhance gene expression in HNSCCs. Defining these novel gene
      signatures and regulatory mechanisms will be important for establishing new
      molecular classifications and subtyping, which in turn will promote development
      of targeted therapeutics for HNSCC.

PMID- 17498292
TI  - First introduction of highly pathogenic H5N1 avian influenza A viruses in wild
      and domestic birds in Denmark, Northern Europe.
AB  - BACKGROUND: Since 2005 highly pathogenic (HP) avian influenza A H5N1 viruses have
      spread from Asia to Africa and Europe infecting poultry, humans and wild birds.
      HP H5N1 virus was isolated in Denmark for the first time in March 2006. A total
      of 44 wild birds were found positive for the HP H5N1 infection. In addition, one
      case was reported in a backyard poultry flock. RESULTS: Full-genome
      characterisation of nine isolates revealed that the Danish H5N1 viruses were
      highly similar to German H5N1 isolates in all genes from the same time period.
      The haemagglutinin gene grouped phylogenetically in H5 clade 2 subclade 2 and
      closest relatives besides the German isolates were isolates from Croatia in 2005,
      Nigeria and Niger in 2006 and isolates from Astrakhan in Russia 2006. The German
      and Danish isolates shared unique substitutions in the NA, PB1 and NS2 proteins.
      CONCLUSION: The first case of HP H5N1 infection of wild and domestic birds in
      Denmark was experienced in March 2006. This is the first full genome
      characterisation of HP H5N1 avian influenza A virus in the Nordic countries. The
      Danish viruses from this time period have their origin from the wild bird strains
      from Qinghai in 2005. These viruses may have been introduced to the Northern
      Europe through unusual migration due to the cold weather in Eastern Europe at
      that time.

PMID- 17498293
TI  - Differential affinity of mammalian histone H1 somatic subtypes for DNA and
      chromatin.
AB  - BACKGROUND: Histone H1 is involved in the formation and maintenance of chromatin
      higher order structure. H1 has multiple isoforms; the subtypes differ in timing
      of expression, extent of phosphorylation and turnover rate. In vertebrates, the
      amino acid substitution rates differ among subtypes by almost one order of
      magnitude, suggesting that each subtype might have acquired a unique function. We
      have devised a competitive assay to estimate the relative binding affinities of
      histone H1 mammalian somatic subtypes H1a-e and H1 degrees for long chromatin
      fragments (30-35 nucleosomes) in physiological salt (0.14 M NaCl) at constant
      stoichiometry. RESULTS: The H1 complement of native chromatin was perturbed by
      adding an additional amount of one of the subtypes. A certain amount of SAR
      (scaffold-associated region) DNA was present in the mixture to avoid
      precipitation of chromatin by excess H1. SAR DNA also provided a set of reference
      relative affinities, which were needed to estimate the relative affinities of the
      subtypes for chromatin from the distribution of the subtypes between the SAR and
      the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so
      as to keep the stoichiometry of perturbed chromatin similar to that of native
      chromatin. H1 molecules freely exchanged between the chromatin and SAR binding
      sites. In conditions of free exchange, H1a was the subtype of lowest affinity,
      H1b and H1c had intermediate affinities and H1d, H1e and H1 degrees the highest
      affinities. Subtype affinities for chromatin differed by up to 19-fold. The
      relative affinities of the subtypes for chromatin were equivalent to those
      estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5
      had an affinity ~12-fold higher than H1e for both DNA and chromatin. CONCLUSION:
      H1 subtypes freely exchange in vitro between chromatin binding sites in
      physiological salt (0.14 M NaCl). The large differences in relative affinity of
      the H1 subtypes for chromatin suggest that differential affinity could be
      functionally relevant and thus contribute to the functional differentiation of
      the subtypes. The conservation of the relative affinities for SAR and non-SAR
      DNA, in spite of a strong preference for SAR sequences, indicates that
      differential affinity alone cannot be responsible for the heterogeneous
      distribution of some subtypes in cell nuclei.

PMID- 17498294
TI  - An annotation infrastructure for the analysis and interpretation of Affymetrix
      exon array data.
AB  - Affymetrix exon arrays contain probesets intended to target every known and
      predicted exon in the entire genome, posing significant challenges for high
      throughput genome-wide data analysis. X:MAP http://xmap.picr.man.ac.uk, an
      annotation database, and exonmap
      http://www.bioconductor.org/packages/2.0/bioc/html/exonmap.html, a BioConductor/R
      package, are designed to support fine-grained analysis of exon array data. The
      system supports the application of standard statistical techniques, prior to the
      use of genome scale annotation to provide gene-, transcript- and exon-level
      summaries and visualization tools.

PMID- 17498295
TI  - Correlates of total physical activity among middle-aged and elderly women.
AB  - Information on correlates of total physical activity (PA) levels among middle
      aged and elderly women is limited. This article aims to investigate whether total
      daily PA levels are associated with age, body mass index, smoking, drinking
      status, and sociodemographic factors. In a cross-sectional study of 38,988 women
      between the ages of 48 and 83 years residing in central Sweden, information on
      PA, weight, height, smoking, drinking, and sociodemographic factors was collected
      through a self-administered questionnaire. Total daily PA levels were measured as
      metabolic equivalents (MET-h/day). Odds ratios (OR) and 95% confidence intervals
      (CI) were estimated by ordinal logistic regression models. We observed decreasing
      level of total PA with increasing age (for 5-year increase: OR = 0.87; 95% CI:
      0.85-0.89) and body mass index (for 5-unit, kg/m2, increase: OR = 0.81; 95% CI:
      0.79-0.84). Multivariable adjusted correlates of total PA level were smoking
      (current vs. never: OR = 0.83; 95% CI: 0.79-0.88), drinking (current vs. never:
      OR = 0.88; 95% CI: 0.82-0.94), educational level (university vs. primary: OR =
      0.54; 95% CI: 0.51-0.58), employment status (housewife vs. full-work: OR = 2.59;
      95% CI: 2.25-2.98), and childhood environment (city vs. countryside: OR = 0.62;
      95% CI: 0.59-0.65). In the present investigation, among middle-aged and elderly
      women, the likelihood of engaging in higher total daily PA levels decreased with
      age, body mass index, educational level, smoking, drinking, and growing up in
      urban places.

PMID- 17498296
TI  - Surfactant protein B polymorphisms are associated with severe respiratory
      syncytial virus infection, but not with asthma.
AB  - BACKGROUND: Surfactant proteins (SP) are important for the innate host defence
      and essential for a physiological lung function. Several linkage and association
      studies have investigated the genes coding for different surfactant proteins in
      the context of pulmonary diseases such as chronic obstructive pulmonary disease
      or respiratory distress syndrome of preterm infants. In this study we tested
      whether SP-B was in association with two further pulmonary diseases in children,
      i. e. severe infections caused by respiratory syncytial virus and bronchial
      asthma. METHODS: We chose to study five polymorphisms in SP-B: rs2077079 in the
      promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in
      intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H.
      Statistical analyses made use of the Armitage's trend test for single
      polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses. RESULTS: The
      polymorphisms rs3024801 and rs3024809 were not present in our study populations.
      The three other polymorphisms were common and in tight linkage disequilibrium
      with each other. They did not show association with bronchial asthma or severe
      RSV infection in the analyses of single polymorphisms. However, haplotypes
      analyses revealed association of SP-B with severe RSV infection (p = 0.034).
      CONCLUSION: Thus our results indicate a possible involvement of SP-B in the
      genetic predisposition to severe RSV infections in the German population. In
      order to determine which of the three polymorphisms constituting the haplotypes
      is responsible for the association, further case control studies on large
      populations are necessary. Furthermore, functional analysis need to be conducted.

PMID- 17498297
TI  - Selection strategy and the design of hybrid oligonucleotide primers for RACE-PCR:
      cloning a family of toxin-like sequences from Agelena orientalis.
AB  - BACKGROUND: The use of specific but partially degenerate primers for nucleic acid
      hybridisations and PCRs amplification of known or unknown gene families was first
      reported well over a decade ago and the technique has been used widely since
      then. RESULTS: Here we report a novel and successful selection strategy for the
      design of hybrid partially degenerate primers for use with RT-PCR and RACE-PCR
      for the identification of unknown gene families. The technique (named PaBaLiS)
      has proven very effective as it allowed us to identify and clone a large group of
      mRNAs encoding neurotoxin-like polypeptide pools from the venom of Agelena
      orientalis species of spider. Our approach differs radically from the generally
      accepted CODEHOP principle first reported in 1998. Most importantly, our method
      has proven very efficient by performing better than an independently generated
      high throughput EST cloning programme. Our method yielded nearly 130 non
      identical sequences from Agelena orientalis, whilst the EST cloning technique
      yielded only 48 non-identical sequences from 2100 clones obtained from the same
      Agelena material. In addition to the primer design approach reported here, which
      is almost universally applicable to any PCR cloning application, our results also
      indicate that venom of Agelena orientalis spider contains a much larger family of
      related toxin-like sequences than previously thought. CONCLUSION: With upwards of
      100,000 species of spider thought to exist, and a propensity for producing
      diverse peptide pools, many more peptides of pharmacological importance await
      discovery. We envisage that some of these peptides and their recombinant
      derivatives will provide a new range of tools for neuroscience research and could
      also facilitate the development of a new generation of analgesic drugs and
      insecticides.

PMID- 17498298
TI  - Demographic changes and marker properties affect detection of human population
      differentiation.
AB  - BACKGROUND: Differentiating genetically between populations is valuable for
      admixture and population stratification detection and in understanding population
      history. This is easy to achieve for major continental populations, but not for
      closely related populations. It has been claimed that a large marker panel is
      necessary to reliably distinguish populations within a continent. We investigated
      whether empirical genetic differentiation could be accomplished efficiently among
      three Asian populations (Hmong, Thai, and Chinese) using a small set of highly
      variable markers (15 tetranucleotide and 17 dinucleotide repeats). RESULTS: Hmong
      could be differentiated from Thai and Chinese based on multi-locus genotypes, but
      Thai and Chinese were indistinguishable from each other. We found significant
      evidence for a recent population bottleneck followed by expansion in the Hmong
      that was not present in the Thai or Chinese. Tetranucleotide repeats were less
      useful than dinucleotide repeat markers in distinguishing between major
      continental populations (Asian, European, and African) while both successfully
      distinguished Hmong from Thai and Chinese. CONCLUSION: Demographic history
      contributes significantly to robust detection of intracontinental population
      structure. Populations having experienced a rapid size reduction may be reliably
      distinguished as a result of a genetic drift -driven redistribution of population
      allele frequencies. Tetranucleotide markers, which differ from dinucleotide
      markers in mutation mechanism and rate, are similar in information content to
      dinucleotide markers in this situation. These factors should be considered when
      identifying populations suitable for gene mapping studies and when interpreting
      interpopulation relationships based on microsatellite markers.

PMID- 17498299
TI  - Thymomas: a cytological and immunohistochemical study, with emphasis on lymphoid
      and neuroendocrine markers.
AB  - BACKGROUND: The current study correlates cytologic morphology with histologic
      type and describes immunophenotypes with a focus on epithelial, neuroendocrine,
      and lymphoid characteristics in an institutional series of surgically excised
      thymomas. METHODS: Fine needle aspirates (FNAs) and surgical specimens were
      retrospectively analyzed, and immunohistochemical stains were performed for EMA,
      cytokeratin 7, cytokeratin 20, CD57 CD5, bcl-2, calretinin, vimentin, CD3, CD20,
      CD1a, CD99 and Ki67. Tumors were classified by WHO criteria. RESULTS: There were
      eleven male and six female patients with an age range of 41 to 84 years (mean, 61
      years) and a male to female ratio of 1.8:1. Four thymomas (4/17, 23.5%) were
      associated with neuromuscular disease: myasthenia gravis (n = 3) and limbic
      encephalitis (n = 1). FNA, under CT guidance, was performed in 7 cases. The
      positive predictive value for thymoma by FNA cytology was 100% and the
      sensitivity was 71%. Thymomas associated with neuromuscular disorders were WHO
      types B2 (n = 1) and B3 (n = 3), and showed a strong expression of CD57 in the
      majority of neoplastic epithelial cells accompanied by large numbers of CD20+
      intratumoral B lymphocytes. Two of seventeen (11.7%) thymomas (all sporadic B3
      type) contained numerous neoplastic epithelial cells positive for CD5 and bcl-2.
      CONCLUSION: Our results suggest that thymomas associated with autoimmune
      disorders contain a significant population of CD20+ intratumoral B lymphocytes.
      Strong CD57 positivity in thymomas may suggest a concomitant neuromuscular
      disorder, notably myasthenia gravis. CD5 expression is of limited value in the
      differential diagnosis of primary thymic epithelial neoplasms since both thymic
      carcinomas and thymomas may express CD5.

PMID- 17498300
TI  - A hierarchical approach employing metabolic and gene expression profiles to
      identify the pathways that confer cytotoxicity in HepG2 cells.
AB  - BACKGROUND: Free fatty acids (FFA) and tumor necrosis factor alpha (TNF-alpha)
      have been implicated in the pathogenesis of many obesity-related metabolic
      disorders. When human hepatoblastoma cells (HepG2) were exposed to different
      types of FFA and TNF-alpha, saturated fatty acid was found to be cytotoxic and
      its toxicity was exacerbated by TNF-alpha. In order to identify the processes
      associated with the toxicity of saturated FFA and TNF-alpha, the metabolic and
      gene expression profiles were measured to characterize the cellular states. A
      computational model was developed to integrate these disparate data to reveal the
      underlying pathways and mechanisms involved in saturated fatty acid toxicity.
      RESULTS: A hierarchical framework consisting of three stages was developed to
      identify the processes and genes that regulate the toxicity. First, discriminant
      analysis identified that fatty acid oxidation and intracellular triglyceride
      accumulation were the most relevant in differentiating the cytotoxic phenotype.
      Second, gene set enrichment analysis (GSEA) was applied to the cDNA microarray
      data to identify the transcriptionally altered pathways and processes. Finally,
      the genes and gene sets that regulate the metabolic responses identified in step
      1 were identified by integrating the expression of the enriched gene sets and the
      metabolic profiles with a multi-block partial least squares (MBPLS) regression
      model. CONCLUSION: The hierarchical approach suggested potential mechanisms
      involved in mediating the cytotoxic and cytoprotective pathways, as well as
      identified novel targets, such as NADH dehydrogenases, aldehyde dehydrogenases
      1A1 (ALDH1A1) and endothelial membrane protein 3 (EMP3) as modulator of the toxic
      phenotypes. These predictions, as well as, some specific targets that were
      suggested by the analysis were experimentally validated.

PMID- 17498301
TI  - Interventions aimed at increasing research use in nursing: a systematic review.
AB  - BACKGROUND: There has been considerable interest recently in developing and
      evaluating interventions to increase research use by clinicians. However, most
      work has focused on medical practices; and nursing is not well represented in
      existing systematic reviews. The purpose of this article is to report findings
      from a systematic review of interventions aimed at increasing research use in
      nursing. OBJECTIVE: To assess the evidence on interventions aimed at increasing
      research use in nursing. METHODS: A systematic review of research use in nursing
      was conducted using databases (Medline, CINAHL, Healthstar, ERIC, Cochrane
      Central Register of Controlled Trials, and Psychinfo), grey literature, ancestry
      searching (Cochrane Database of Systematic Reviews), key informants, and manual
      searching of journals. Randomized controlled trials and controlled before- and
      after-studies were included if they included nurses, if the intervention was
      explicitly aimed at increasing research use or evidence-based practice, and if
      there was an explicit outcome to research use. Methodological quality was
      assessed using pre-existing tools. Data on interventions and outcomes were
      extracted and categorized using a pre-established taxonomy. RESULTS: Over 8,000
      titles were screened. Three randomized controlled trials and one controlled
      before- and after-study met the inclusion criteria. The methodological quality of
      included studies was generally low. Three investigators evaluated single
      interventions. The most common intervention was education. Investigators measured
      research use using a combination of surveys (three studies) and compliance with
      guidelines (one study). Researcher-led educational meetings were ineffective in
      two studies. Educational meetings led by a local opinion leader (one study) and
      the formation of multidisciplinary committees (one study) were both effective at
      increasing research use. CONCLUSION: Little is known about how to increase
      research use in nursing, and the evidence to support or refute specific
      interventions is inconclusive. To advance the field, we recommend that
      investigators: (1) use theoretically informed interventions to increase research
      use, (2) measure research use longitudinally using theoretically informed and
      psychometrically sound measures of research use, as well as, measuring patient
      outcomes relevant to the intervention, and (3) use more robust and
      methodologically sound study designs to evaluate interventions. If investigators
      aim to establish a link between using research and improved patient outcomes they
      must first identify those interventions that are effective at increasing research
      use.

PMID- 17498302
TI  - Pre-apoptotic response to therapeutic DNA damage involves protein modulation of
      Mcl-1, Hdm2 and Flt3 in acute myeloid leukemia cells.
AB  - BACKGROUND: Acute myeloid leukemia (AML) cells are characterized by non-mutated
      TP53, high levels of Hdm2, and frequent mutation of the Flt3 receptor tyrosine
      kinase. The juxtamembrane mutation of FLT3 is the strongest independent marker
      for disease relapse and is associated with elevated Bcl-2 protein and p53 hyper
      phosphorylation in AML. DNA damage forms the basic mechanism of cancer cell
      eradication in current therapy of AML. Hdm2 and pro-apoptotic Bcl-2 members are
      among the most intensely induced genes immediately after chemotherapy and Hdm2 is
      proposed a role in receptor tyrosine kinase regulation. Thus we examined the DNA
      damage related modulation of these proteins in relation to FLT3 mutational status
      and induction of apoptosis. RESULTS: Within one hour after exposure to ionizing
      radiation (IR), the AML cells (NB4, MV4-11, HL-60, primary AML cells) showed an
      increase in Flt3 protein independent of mRNA levels, while the Hdm2 protein
      decreased. The FLT3 mutant MV4-11 cells were resistant to IR accompanied by
      presence of both Mcl-1 and Hdm2 protein three hours after IR. In contrast, the
      FLT3 wild type NB4 cells responded to IR with apoptosis and pre-apoptotic Mcl-1
      down regulation. Daunorubicin (DNR) induced continuing down regulation of Hdm2
      and Mcl-1 in both cell lines followed by apoptosis. CONCLUSION: Both IR and DNR
      treatment resulted in concerted protein modulations of Mcl-1, Hdm2 and Flt3. Cell
      death induction was associated with persistent attenuation of Mcl-1 and Hdm2.
      These observations suggest that defining the pathway(s) modulating Flt3, Hdm2 and
      Mcl-1 may propose new strategies to optimize therapy for the relapse prone FLT3
      mutated AML patients.

PMID- 17498303
TI  - Expansion and evolution of insect GMC oxidoreductases.
AB  - BACKGROUND: The GMC oxidoreductases comprise a large family of diverse FAD
      enzymes that share a homologous backbone. The relationship and origin of the GMC
      oxidoreductase genes, however, was unknown. Recent sequencing of entire genomes
      has allowed for the evolutionary analysis of the GMC oxidoreductase family.
      RESULTS: Although genes that encode enzyme families are rarely linked in higher
      eukaryotes, we discovered that the majority of the GMC oxidoreductase genes in
      the fruit fly (D. melanogaster), mosquito (A. gambiae), honeybee (A. mellifera),
      and flour beetle (T. castaneum) are located in a highly conserved cluster
      contained within a large intron of the flotillin-2 (Flo-2) gene. In contrast, the
      genomes of vertebrates and the nematode C. elegans contain few GMC genes and lack
      a GMC cluster, suggesting that the GMC cluster and the function of its resident
      genes are unique to insects or arthropods. We found that the development patterns
      of expression of the GMC cluster genes are highly complex. Among the GMC
      oxidoreductases located outside of the GMC gene cluster, the identities of two
      related enzymes, glucose dehydrogenase (GLD) and glucose oxidase (GOX), are
      known, and they play major roles in development and immunity. We have discovered
      that several additional GLD and GOX homologues exist in insects but are remotely
      similar to fungal GOX. CONCLUSION: We speculate that the GMC oxidoreductase
      cluster has been conserved to coordinately regulate these genes for a common
      developmental or physiological function related to ecdysteroid metabolism.
      Furthermore, we propose that the GMC gene cluster may be the birthplace of the
      insect GMC oxidoreductase genes. Through tandem duplication and divergence within
      the cluster, new GMC genes evolved. Some of the GMC genes have been retained in
      the cluster for hundreds of millions of years while others might have transposed
      to other regions of the genome. Consistent with this hypothesis, our analysis
      indicates that insect GOX and GLD arose from a different ancestral GMC gene than
      that of fungal GOX.

PMID- 17498304
TI  - How accurate and statistically robust are catalytic site predictions based on
      closeness centrality?
AB  - BACKGROUND: We examine the accuracy of enzyme catalytic residue predictions from
      a network representation of protein structure. In this model, amino acid alpha
      carbons specify vertices within a graph and edges connect vertices that are
      proximal in structure. Closeness centrality, which has shown promise in previous
      investigations, is used to identify important positions within the network.
      Closeness centrality, a global measure of network centrality, is calculated as
      the reciprocal of the average distance between vertex i and all other vertices.
      RESULTS: We benchmark the approach against 283 structurally unique proteins
      within the Catalytic Site Atlas. Our results, which are inline with previous
      investigations of smaller datasets, indicate closeness centrality predictions are
      statistically significant. However, unlike previous approaches, we specifically
      focus on residues with the very best scores. Over the top five closeness
      centrality scores, we observe an average true to false positive rate ratio of 6.8
      to 1. As demonstrated previously, adding a solvent accessibility filter
      significantly improves predictive power; the average ratio is increased to 15.3
      to 1. We also demonstrate (for the first time) that filtering the predictions by
      residue identity improves the results even more than accessibility filtering.
      Here, we simply eliminate residues with physiochemical properties unlikely to be
      compatible with catalytic requirements from consideration. Residue identity
      filtering improves the average true to false positive rate ratio to 26.3 to 1.
      Combining the two filters together has little affect on the results. Calculated p
      values for the three prediction schemes range from 2.7E-9 to less than 8.8E-134.
      Finally, the sensitivity of the predictions to structure choice and slight
      perturbations is examined. CONCLUSION: Our results resolutely confirm that
      closeness centrality is a viable prediction scheme whose predictions are
      statistically significant. Simple filtering schemes substantially improve the
      method's predicted power. Moreover, no clear effect on performance is observed
      when comparing ligated and unligated structures. Similarly, the CC prediction
      results are robust to slight structural perturbations from molecular dynamics
      simulation.

PMID- 17498305
TI  - The combined effect of two mutations that alter serially homologous color pattern
      elements on the fore and hindwings of a butterfly.
AB  - BACKGROUND: The ability for serially homologous structures to acquire a separate
      identity has been primarily investigated for structures dependent on Hox gene
      input but is still incompletely understood in other systems. The fore and
      hindwings of butterflies are serially homologous structures as are the serially
      homologous eyespots that can decorate each of these wings. Eyespots can vary in
      number between fore and hindwings of the same individual and mutations of large
      effect can control the total number of eyespots that each of the wings displays.
      Here we investigate the genetics of a new spontaneous color pattern mutation,
      Missing, that alters eyespot number in the nymphalid butterfly, Bicyclus anynana.
      We further test the interaction of Missing with a previously described mutation,
      Spotty, describe the developmental stage affected by Missing, and test whether
      Missing is a mutant variant of the gene Distal-less via a linkage association
      study. RESULTS: Missing removes or greatly reduces the size of two of the
      hindwing eyespots from the row of seven eyespots, with no detectable effect on
      the rest of the wing pattern. Offspring carrying a single Missing allele display
      intermediate sized eyespots at these positions. Spotty has the opposite effect of
      Missing, i.e., it introduces two extra eyespots in homologous wing positions to
      those affected by Missing, but on the forewing. When Missing is combined with
      Spotty the size of the two forewing eyespots decreases but the size of the
      hindwing spots stays the same, suggesting that these two mutations have a
      combined effect on the forewing such that Missing reduces eyespot size when in
      the presence of a Spotty mutant allele, but that Spotty has no effect on the
      hindwing. Missing prevents the complete differentiation of two of the eyespot
      foci on the hindwing. We found no evidence for any linkage between the Distal
      less and Missing genes. CONCLUSION: The spontaneous mutation Missing controls the
      differentiation of the signaling centers of a subset of the serial homologous
      eyespots present on both the fore and the hindwing in a dose-dependent fashion.
      The effect of Missing on the forewing, however, is only observed when the
      mutation Spotty introduces additional eyespots on this wing. Spotty, on the other
      hand, controls the differentiation of eyespot centers only on the forewing.
      Spotty, unlike Missing, may be under Ubx gene regulation, since it affects a
      subset of eyespots on only one of the serially homologous wings.

PMID- 17498306
TI  - Macular pigment response to a supplement containing meso-zeaxanthin, lutein and
      zeaxanthin.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a disease with multiple
      risk factors, many of which appear to involve oxidative stress. Macular pigment,
      with its antioxidant and light-screening properties, is thought to be protective
      against AMD. A result has been the appearance of dietary supplements containing
      the macular carotenoids, lutein and zeaxanthin. More recently, a supplement has
      been marketed containing, in addition, the third major carotenoid of the macular
      pigment, meso-zeaxanthin. The purpose of the study was to determine the
      effectiveness of such a supplement in raising macular pigment density in human
      subjects. METHODS: A 120 day supplementation study was conducted in which 10
      subjects were given gel-caps that provided 20 mg/day of predominantly meso
      zeaxanthin, with smaller amounts of lutein and zeaxanthin. A second group of 9
      subjects were given gel caps containing a placebo for the same 120 day period.
      Prior to and during the supplementation period, blood serum samples were analyzed
      by high performance liquid chromatography for carotenoid content. Similarly,
      macular pigment optical density was measured by heterochromatic flicker
      photometry. Differences in response between the supplementation and placebo
      groups were tested for significance using a student's t-test. RESULTS: During
      supplementation with the carotenoids, blood samples revealed the presence of all
      three carotenoids. Macular pigment optical density, measured at 460 nm, rose at
      an average rate of 0.59 +/- 0.79 milli-absorbance unit/day in the 10 supplemented
      subjects. This was significantly different from the placebo group (9 subjects)
      for whom the average rate was -0.17 +/- 0.42 milli-absorbance units/day.
      CONCLUSION: We have shown for the first time that meso-zeaxanthin is absorbed
      into the serum following ingestion. The data indicate that a supplement
      containing predominantly meso-zeaxanthin is generally effective at raising
      macular pigment density, and may turn out to be a useful addition to the defenses
      against AMD.

PMID- 17498307
TI  - Does reservoir host mortality enhance transmission of West Nile virus?
AB  - BACKGROUND: Since its 1999 emergence in New York City, West Nile virus (WNV) has
      become the most important and widespread cause of mosquito-transmitted disease in
      North America. Its sweeping spread from the Atlantic to the Pacific coast was
      accompanied by widespread mortality among wild birds, especially corvids. Only
      sporadic avian mortality had previously been associated with this infection in
      the Old World. Here, we examine the possibility that reservoir host mortality may
      intensify transmission, both by concentrating vector mosquitoes on remaining
      hosts and by preventing the accumulation of "herd immunity". RESULTS: Inspection
      of the Ross-Macdonald expression of the basic reproductive number (R0) suggests
      that this quantity may increase with reservoir host mortality. Computer
      simulation confirms this finding and indicates that the level of virulence is
      positively associated with the numbers of infectious mosquitoes by the end of the
      epizootic. The presence of reservoir incompetent hosts in even moderate numbers
      largely eliminated the transmission-enhancing effect of host mortality. Local
      host die-off may prevent mosquitoes to "waste" infectious blood meals on immune
      host and may thus facilitate perpetuation and spread of transmission. CONCLUSION:
      Under certain conditions, host mortality may enhance transmission of WNV and
      similarly maintained arboviruses and thus facilitate their emergence and spread.
      The validity of the assumptions upon which this argument is built need to be
      empirically examined.

PMID- 17498308
TI  - Worksite environment physical activity and healthy food choices: measurement of
      the worksite food and physical activity environment at four metropolitan bus
      garages.
AB  - BACKGROUND: The present research describes a measure of the worksite environment
      for food, physical activity and weight management. The worksite environment
      measure (WEM instrument) was developed for the Route H Study, a worksite
      environmental intervention for weight gain prevention in four metro transit bus
      garages in Minneapolis-St. Paul. METHODS: Two trained raters visited each of the
      four bus garages and independently completed the WEM. Food, physical activity and
      weight management-related items were observed and recorded on a structured form.
      Inter-rater reliability was computed at the item level using a simple percentage
      agreement. RESULTS: The WEM showed high inter-rater reliability for the number
      and presence of food-related items. All garages had vending machines, microwaves
      and refrigerators. Assessment of the physical activity environment yielded
      similar reliability for the number and presence/absence of fitness items. Each
      garage had a fitness room (average of 4.3 items of fitness equipment). All
      garages had at least one stationary bike and treadmill. Three garages had at
      least one weighing scale available. There were no designated walking areas inside
      or outside. There were on average < 1 food stores or restaurants within sight of
      each garage. Few vending machine food and beverage items met criteria for
      healthful choices (15% of the vending machine foods; 26% of the vending machine
      beverages). The garage environment was perceived to be not supportive of healthy
      food choices, physical activity and weight management; 52% reported that it was
      hard to get fruits and vegetables in the garages, and 62% agreed that it was hard
      to be physically active in the garages. CONCLUSION: The WEM is a reliable measure
      of the worksite nutrition, physical activity, and weight management environment
      that can be used to assess changes in the work environment.

PMID- 17498310
TI  - Media and education play a tremendous role in mounting AIDS awareness among
      married couples in Bangladesh.
AB  - BACKGROUND: To quarantine the spreading possibility of HIV virus to general
      population boosting public awareness is must. But the proper awareness level is
      substantially low in Bangladesh. This paper aims to identify the factors
      associated with the awareness regarding HIV/AIDS through a bivariate and
      multivariate analysis using the data extracted from Bangladesh Demography and
      Health Survey (BDHS) 1999-2000. RESULTS: The findings of both techniques show
      that education, occupation, socioeconomic status, status of household food
      consumption, area of residence and media exposure have significant (p < 0.001)
      contribution in determining HIV/AIDS awareness level. It also reveals that media,
      particularly TV, and education play the leading role regarding this issue while
      the others have an indirect relationship. The odds of awareness among higher
      educated women and men were 4.69 and 77.73 times of no educated women and men
      respectively. In addition, both women and men those who regularly watch TV were
      8.6 times more likely to be aware about AIDS compared to those who never watch
      TV. This phenomenon holds true for both women and men. CONCLUSION: At this
      instant it is urgent to give emphasis on education, alleviation of poverty,
      ensuring electronic media exposure, head to head communication program,
      institutional based sex education and necessary information to learn about
      HIV/AIDS for the young, adult and adolescents all over the country.

PMID- 17498309
TI  - Human immunodeficiency virus type 1 efficiently binds to human fetal astrocytes
      and induces neuroinflammatory responses independent of infection.
AB  - BACKGROUND: HIV-1 infects human astrocytes in vitro and in vivo but the frequency
      of infected cells is low and its biological significance is unknown. In studies
      in vitro, recombinant gp120 alone can induce profound effects on astrocyte
      biology, suggesting that HIV-1 interaction with astrocytes and its functional
      consequences extend beyond the limited levels of infection in these cells. Here
      we determined the relative efficiencies of HIV-1 binding and infection in human
      fetal astrocytes (HFA), mainly at the single cell level, using HIV-1 tagged with
      green fluorescence protein (GFP)-Vpr fusion proteins, termed HIV-GFP, to detect
      virus binding and HIV-1 expressing Rev and NefGFP fusion proteins to detect
      productive infection. RESULTS: Essentially all HFA in a population bound HIV-GFP
      specifically and independently of CCR5 and CXCR4. The dynamics of this binding at
      37 degrees C resembled binding of an HIV fusion mutant to CD4-positive cells,
      indicating that most of HIV-GFP arrested infection of HFA at the stage of virus
      cell fusion. Despite extensive binding, only about 1% of HFA were detectably
      infected by HIV-RevGFP or HIV-NefGFP, but this proportion increased to the
      majority of HFA when the viruses were pseudotyped with vesicular stomatitis virus
      envelope glycoprotein G, confirming that HFA impose a restriction upon HIV-1
      entry. Exposure of HFA to HIV-1 through its native proteins rapidly induced
      synthesis of interleukin-6 and interleukin-8 with increased mRNA detected within
      3 h and increased protein detected within 18 h of exposure. CONCLUSION: Our
      results indicate that HIV-1 binding to human astrocytes, although extensive, is
      not generally followed by virus entry and replication. Astrocytes respond to HIV
      1 binding by rapidly increased cytokine production suggesting a role of this
      virus-brain cell interaction in HIV-1 neuropathogenesis.

PMID- 17498311
TI  - Gastrointestinal stromal tumour in Meckel's diverticulum.
AB  - BACKGROUND: Meckel's Diverticulum is the most commonly encountered congenital
      anomaly of the small intestine, occurring in approximately 2% of the population.
      Occasionally Meckel's diverticulum harbors neoplasms. CASE PRESENTATION: A 65
      year old gentleman, presented with a pelvic mass. On exploratory laparotomy, it
      turned out to be gastrointestinal stromal tumour (GIST) arising from Meckel's
      diverticulum. Short history and review of literature are discussed. CONCLUSION:
      Neoplasms occurring from Meckel's diverticulum, even though rare, should be
      considered as differential diagnosis of pelvic masses arising from bowel,
      wherever imaging modalities fail to give a definitive diagnosis.

PMID- 17498312
TI  - Cooling and hemodynamic management in heatstroke: practical recommendations.
AB  - INTRODUCTION: Although rapid cooling and management of circulatory failure are
      crucial to the prevention of irreversible tissue damage and death in heatstroke,
      the evidence supporting the optimal cooling method and hemodynamic management has
      yet to be established. METHODS: A systematic review of all clinical studies
      published in Medline (1966 to 2006), CINAHL (Cumulative Index to Nursing & Allied
      Health Literature) (1982 to 2006), and Cochrane Database was performed using the
      OVID interface without language restriction. Search terms included heatstroke,
      sunstroke, and heat stress disorders. RESULTS: Fourteen articles reported
      populations subjected to cooling treatment for classic or exertional heatstroke
      and included data on cooling time, neurologic morbidity, or mortality. Five
      additional articles described invasive monitoring with central venous or
      pulmonary artery catheters. The four clinical trials and 15 observational studies
      covered a total of 556 patients. A careful analysis of the results obtained
      indicated that the cooling method based on conduction, namely immersion in iced
      water, was effective among young people, military personnel, and athletes with
      exertional heatstroke. There was no evidence to support the superiority of any
      one cooling technique in classic heatstroke. The effects of non-invasive,
      evaporative, or conductive-based cooling techniques, singly or combined, appeared
      to be comparable. No evidence of a specific endpoint temperature for safe
      cessation of cooling was found. The circulatory alterations in heatstroke were
      due mostly to a form of distributive shock associated with relative or absolute
      hypovolemia. Myocardial failure was found to be rare. CONCLUSION: A systematic
      review of the literature failed to identify reliable clinical data on the optimum
      treatment of heatstroke. Nonetheless, the findings of this study could serve as a
      framework for preliminary recommendations in cooling and hemodynamic management
      of heatstroke until more evidence-based data are generated.

PMID- 17498313
TI  - Helicobacter pylori in colorectal neoplasms: is there an aetiological
      relationship?
AB  - BACKGROUND: This pilot study was carried out to determine whether Helicobacter
      pylori can be detected in normal colon or in association with colorectal
      neoplasia. METHODS: Paraffin processed colonic tissue blocks of normal colonic
      mucosa (n = 60), and patients diagnosed as adenoma (n = 60), and adenocarcinoma
      (n = 60) were retrieved from our archive; the adenoma group included tubular (n =
      20), tubulovillous (n = 20) and villous adenomas (n = 20). 4 mum sections were
      stained by immunohistochemical methods using anti-Helicobacter pylori antibodies
      (polyclonal NCL-HPp and monoclonal NCL-C-jejuni). RESULTS: Significant numbers of
      Helicobacter pylori were identified in tubular adenomas (OR = 11.13; 95%CI = 1.62
      76.70), tubulovillous adenomas (OR = 10.45; 95%CI = 1.52-71.52) and
      adenocarcinomas (OR = 8.13; 95%CI = 1.40-46.99) compared to controls: there was
      no association in numbers of Helicobacter pylori and villous adenomas (OR = 2.95;
      95%CI = 0.29-9.96). CONCLUSION: We conclude that although, in this pilot study,
      there appears to be an association in the prevalence of Helicobacter pylori with
      some, but not all, colorectal neoplasms, we can not infer causality from these
      results. These findings need to be further substantiated with a prospective study
      and the use of molecular biological techniques to determine a causal association.

PMID- 17498314
TI  - Mast cell density in gastric biopsies of pediatric age group and its relation to
      inflammation and presence of Helicobacter pylori.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      mast cell density, histological severity of gastritis, and presence of
      Helicobacter pylori (H. pylori) in the antral mucosa of pediatric patients.
      METHODS: The study included 352 (192 male and 160 female, < 14 years old)
      patients. All cases underwent endoscopy, and biopsies were obtained for
      histopathological examination and evaluation of Helicobacter pylori. All biopsies
      were evaluated according to the Sydney system and mast cell density in the antral
      mucosa was analyzed by Giemsa stain. Spearman's correlation test was used to
      determine the relationship between mast cell density and other histopathological
      parameters. The comparison of mast cell density between H. pylori positive and
      negative groups was analyzed by Mann Whitney U test. RESULTS: Mast cell density
      was 12.6 +/- 0.87 in 0.25 mm2 (0-81). Means of severity of gastric inflammation
      in H. pylori-positive and negative patients were 1.7 +/- 0.6 and 0.6 +/- 0.7,
      respectively, which was statistically significant (p = 0.0001). Mast cell density
      was not correlated with presence and degree of inflammation, activity, presence
      and score of H. pylori in the antrum (p > 0.05). There was no significant
      correlation between mast cell density and allergy. DISCUSSION: We concluded that
      there may be some other ways for contribution of mast cells in pathologic
      processes involving gastrointestinal tract in children.

PMID- 17498315
TI  - Sequence variations in DNA repair gene XPC is associated with lung cancer risk in
      a Chinese population: a case-control study.
AB  - BACKGROUND: The nucleotide excision repair (NER) protein, xeroderma pigmentosum C
      (XPC), participates in recognizing DNA lesions and initiating DNA repair in
      response to DNA damage. Because mutations in XPC cause a high risk of cancer in
      XP patients, we hypothesized that inherited sequence variations in XPC may alter
      DNA repair and thus susceptibility to cancer. METHODS: In this hospital-based
      case-control study, we investigated five XPC tagging, common single nucleotide
      polymorphisms (tagging SNPs) in 1,010 patients with newly diagnosed lung cancer
      and 1,011 matched cancer free controls in a Chinese population. RESULTS: In
      individual tagging SNP analysis, we found that rs3731055AG+AA variant genotypes
      were associated with a significantly decreased risk of lung adenocarcinoma
      [adjusted odds ratio (OR), 0.71; 95% confidence interval (CI), 0.56-0.90] but an
      increased risk of small cell carcinomas [adjusted OR, 1.79; 95% CI, 1.05-3.07].
      Furthermore, we found that haplotype ACCCA was associated with a decreased risk
      of lung adenocarcinoma [OR, 0.78; 95% CI, 0.62-0.97] but an increased risk of
      small cell carcinomas [OR, 1.68; 95% CI, 1.04-2.71], which reflected the presence
      of rs3731055A allele in this haplotype. Further stratified analysis revealed that
      the protective effect of rs3731055AG+AA on risk of lung adenocarcinoma was more
      evident among young subjects (age < or= 60) and never smokers. CONCLUSION: These
      results suggest that inherited sequence variations in XPC may modulate risk of
      lung cancer, especially lung adenocarcinoma, in Chinese populations. However,
      these findings need to be verified in larger confirmatory studies with more
      comprehensively selected tagging SNPs.

PMID- 17498316
TI  - Enrolling adolescents in HIV vaccine trials: reflections on legal complexities
      from South Africa.
AB  - BACKGROUND: South Africa is likely to be the first country in the world to host
      an adolescent HIV vaccine trial. Adolescents may be enrolled in late 2007. In the
      development and review of adolescent HIV vaccine trial protocols there are many
      complexities to consider, and much work to be done if these important trials are
      to become a reality. DISCUSSION: This article sets out essential requirements for
      the lawful conduct of adolescent research in South Africa including compliance
      with consent requirements, child protection laws, and processes for the ethical
      and regulatory approval of research. SUMMARY: This article outlines likely
      complexities for researchers and research ethics committees, including
      determining that trial interventions meet current risk standards for child
      research. Explicit recommendations are made for role-players in other
      jurisdictions who may also be planning such trials. This article concludes with
      concrete steps for implementing these important trials in South Africa and other
      jurisdictions, including planning for consent processes; delineating privacy
      rights; compiling information necessary for ethics committees to assess risks to
      child participants; training trial site staff to recognize when disclosures trig
      mandatory reporting response; networking among relevant ethics committees; and
      lobbying the National Regulatory Authority for guidance.

PMID- 17498317
TI  - Age standardisation - an indigenous standard?
AB  - The study of inequities in health is a critical component of monitoring
      government obligations to uphold the rights of Indigenous Peoples. In
      Aotearoa/New Zealand the indigenous Maori population has a substantially younger
      age structure than the non-indigenous population making it necessary to account
      for age differences when comparing population health outcomes. An age
      standardised rate is a summary measure of a rate that a population would have if
      it had a standard age structure. Changing age standards have stimulated interest
      in the potential impact of population standards on disparities data and
      consequently on health policy. This paper compares the age structure of the Maori
      and non-Maori populations with two standard populations commonly used in New
      Zealand: Segi's world and WHO world populations. The performance of these
      standards in Maori and non-Maori mortality data was then measured against the use
      of the Maori population as a standard. It was found that the choice of population
      standard affects the magnitude of mortality rates, rate ratios and rate
      differences, the relative ranking of causes of death, and the relative width of
      confidence intervals. This in turn will affect the monitoring of trends in health
      outcomes and health policy decision-making. It is concluded that the choice of
      age standard has political implications and the development and utilisation of an
      international indigenous population standard should be considered.

PMID- 17498318
TI  - Cardiac asthma in elderly patients: incidence, clinical presentation and outcome.
AB  - BACKGROUND: Cardiac asthma is common, but has been poorly investigated. The
      objective was to compare the characteristics and outcome of cardiac asthma with
      that of classical congestive heart failure (CHF) in elderly patients. METHODS:
      Prospective study in an 1,800-bed teaching hospital. RESULTS: Two hundred and
      twelve consecutive patients aged > or = 65 years presenting with dyspnea due to
      CHF (mean age of 82 +/- 8 years) were included. Findings of cardiac
      echocardiography and natriuretic peptides levels were used to confirm CHF.
      Cardiac asthma patients were defined as a patient with CHF and wheezing reported
      by attending physician upon admission to the emergency department. The CHF group
      (n = 137) and the cardiac asthma group (n = 75), differed for tobacco use (34%
      vs. 59%, p < 0.05), history of chronic obstructive pulmonary disease (16% vs.
      47%, p < 0.05), peripheral arterial disease (10% vs. 24%, p < 0.05). Patients
      with cardiac asthma had a significantly lower pH (7.38 +/- 0.08 vs. 7.43 +/-
      0.06, p < 0.05), and a higher PaCO2 (47 +/- 15 vs. 41 +/- 11 mmHg, p < 0.05) at
      admission. In the cardiac asthma group, patients had greater distal airway
      obstruction: forced expiratory volume in 1 second of 1.09 vs. 1.33 Liter (p <
      0.05), and a forced expiratory flow at 25% to 75% of vital capacity of 0.76 vs.
      0.99 Liter (p < 0.05). The in-hospital (23% vs. 19%) and one year mortality (48%
      vs. 43%) rates were similar. CONCLUSION: Patients with cardiac asthma represented
      one third of CHF in elderly patients. They were more hypercapnic and experienced
      more distal airway obstruction. However, outcomes were similar.

PMID- 17498319
TI  - Improved cardiac arrest outcomes: as time goes by?
AB  - In a recent issue of Critical Care, Mally and colleagues reported outcomes from
      an observational study of out-of-hospital cardiac arrests in Slovenia.
      Multivariable analysis identified independent predictors for hospital discharge,
      including higher end-tidal carbon dioxide (ETCO2) levels, higher mean arterial
      pressure (MAP) and the recency (years) of the arrest. ETCO2 has been previously
      demonstrated to correlate with cardiac index, and predict successful
      resuscitation. Initial ETCO2 reflects the initial adequacy of resuscitation, and
      the ETCO2 on admission to hospital reflects a number of factors, including the
      adequacy of ventilation. During resuscitation, coronary perfusion pressure
      appears important for survival, but there are limited human data to guide
      hemodynamic management after cardiac arrest. A higher blood pressure could
      represent more vasoconstriction, less vasodilation, avoidance of
      hyperventilation, or a better cardiac output. Improved hospital discharge was
      also observed during the later years of the study. During this period a number of
      factors could have contributed to the improved outcome. These include new
      guidelines, the awareness of the importance of good CPR (including avoidance of
      hyperventilation), and better post-resuscitation care (including therapeutic
      hypothermia). It is hard to unravel the actual contribution of these factors to
      the final outcome, but the authors should be commended for their excellent
      overall results, and their thought provoking manuscript.

PMID- 17498320
TI  - Is the adapted Radimer/Cornell questionnaire valid to measure food insecurity of
      urban households in Tehran, Iran?
AB  - OBJECTIVE: To assess the validity of the adapted Radimer/Cornell questionnaire to
      measure food insecurity in low-income urban households in Tehran, the capital of
      Iran. DESIGN: The Radimer/Cornell questionnaire was modified and used to assess
      the applicability, validity and reliability of such a measure in a culturally
      different context of urban households in Tehran. Factor analysis and Cronbach's
      alpha were used to assess validity and reliability, respectively. Socio-economic
      characteristics and food consumption frequency of the household were used to
      assess the criterion validity of the questionnaire. SETTING: District 20 of
      Tehran. SUBJECTS: A sample of 250 Iranian nuclear households with at least one
      child aged 1-18 years and a non-pregnant, non-lactating woman of reproductive
      age, selected through a multistage random sampling method. RESULTS: Three scales,
      labelled as household, individual and child hunger, were extracted through factor
      analysis using varimax rotation. Internal consistency of the scales was 0.897,
      0.820 and 0.796, respectively. Individual insecurity and child hunger were
      inversely correlated with monthly per capita income, father's education, mother's
      education and father's occupational status, and positively correlated with
      household size, as expected. However, household insecurity did not follow the
      same pattern. Consumption frequency of fruits, vegetables, dairy, red meat and
      rice declined as food insecurity status worsened, while bread and potato
      consumption increased. CONCLUSION: The results show that a modified version of
      the Radimer/Cornell questionnaire is a valid and reliable instrument to measure
      household food insecurity in a culturally different context. However, further
      modifications seem necessary to measure food insecurity at household level.
      Results lend support to the utility and applicability of experience-based
      measures in varying cultural communities.

PMID- 17498321
TI  - Religious involvement and depressive symptoms in primary care elders.
AB  - BACKGROUND: Multiple lines of evidence indicate relationships between religious
      involvement and depression, although the specific nature of the relationships is
      yet to be clarified. Moreover, there appear to be no well controlled longitudinal
      studies to date examining this issue in primary care elders. METHOD: The authors
      assessed the linear and non-linear relationships between three commonly
      identified types of religious involvement and observer-rated depressive symptoms
      in 709 primary care elders assessed at baseline and 1-year follow-up. RESULTS:
      Cross-sectional analyses revealed a curvilinear, U-shaped association between
      depressive symptoms and organizational religious activity, an inverse linear
      relationship of depressive symptoms with private religious involvement, and a
      positive relationship of depressive symptoms with intrinsic religiosity.
      Longitudinal analyses revealed a U-shaped association between depressive symptoms
      and private religious involvement, such that those reporting moderate levels of
      private religiosity at baseline evidenced lower levels of depressive symptoms at
      1-year follow-up than those reporting either high or low levels of private
      religious activity. CONCLUSIONS: The relationships between religious involvement
      and depression in primary care elders are complex and dependent on the type of
      religiosity measured. The authors found the strongest evidence for an association
      of non-organizational, private religious involvement and the severity of
      depressive symptoms, although further study is warranted using carefully
      controlled longitudinal designs that test for both linear and curvilinear
      relationships.

PMID- 17498322
TI  - The role of self-reported impulsivity and reward sensitivity versus
      neurocognitive measures of disinhibition and decision-making in the prediction of
      relapse in pathological gamblers.
AB  - BACKGROUND: Disinhibition and decision-making skills play an important role in
      theories on the cause and outcome of addictive behaviors such as substance use
      disorders and pathological gambling. In recent studies, both disinhibition and
      disadvantageous decision-making strategies, as measured by neurocognitive tests,
      have been found to influence the course of substance use disorders. Research on
      factors affecting relapse in pathological gambling is scarce. METHOD: This study
      investigated the effect of both self-reported impulsivity and reward sensitivity,
      and neurocognitively assessed disinhibition and decision-making under conflicting
      contingencies, on relapse in a group of 46 pathological gamblers. RESULTS:
      Logistic regression analysis indicated that longer duration of the disorder and
      neurocognitive indicators of disinhibition (Stop Signal Reaction Time) and
      decision-making (Card Playing Task) were significant predictors of relapse
      (explaining 53% of the variance in relapse), whereas self-reported impulsivity
      and reward sensitivity did not significantly predict relapse. Overall
      classification accuracy was 76%, with a positive classification accuracy of 76%
      and a negative classification accuracy of 75%. CONCLUSIONS: Duration of the
      disorder and neurocognitive measures of disinhibition and decision-making are
      powerful predictors of relapse in pathological gambling. The results suggest that
      endophenotypical neurocognitive characteristics are more promising in the
      prediction of relapse in pathological gambling than phenotypical personality
      characteristics. Neurocognitive predictors may be useful to guide treatment
      planning of follow-up contacts and booster sessions.

PMID- 17498323
TI  - The vein of Labbe masquerading as an epidural abscess.
AB  - The occipitotemporal vein (OTV) courses over the temporal lobe, connecting the
      superficial middle cerebral vein and the transverse sinus. This vein is rarely
      identifiable on computerized tomography (CT) scans and a large amount of contrast
      is needed to identify such a relatively small vessel. We present a 12-month-old
      male with acute coalescent mastoiditis and a subperiosteal abscess. An epidural
      abscess was suspected on pre-operative CT scan. No abscess was found on surgery.
      Based on the surgical finding, we determined that this misdiagnosis was due to a
      vascular variant, the occipitotemporal vein (vein of Labbe) that masqueraded as
      an abscess on the CT scan. Recognition of the vein of Labbe on CT scan is
      therefore essential for the appropriate management of otological and
      neurotological disease.

PMID- 17498324
TI  - Severe laryngitis following chronic anabolic steroid abuse.
AB  - The effects of anabolic steroids on the quality of voice have been well
      documented; however, no study has established significant structural changes in
      the larynx as a direct result of anabolic steroid use. We report a unique case of
      a 47-year-old male smoker and professional body builder who presented with
      progressive stridor and hoarseness following abuse of anabolic steroids over a
      period of two years. Conservative management failed to resolve his symptoms and a
      planned tracheostomy was performed to secure his airway. Subsequently he was
      treated with multiple laser resections and eventually decannulated. No case of
      severe laryngitis in association with anabolic steroid usage has been reported
      previously in the literature.

PMID- 17498325
TI  - Optimising outcome assessment of voice interventions, II: Sensitivity to change
      of self-reported and observer-rated measures.
AB  - OBJECTIVES: A wide range of well validated instruments is now available to assess
      voice quality and voice-related quality of life, but comparative studies of the
      responsiveness to change of these measures are lacking. The aim of this study was
      to assess the responsiveness to change of a range of different measures,
      following voice therapy and surgery. DESIGN: Longitudinal, cohort comparison
      study. SETTING: Two UK voice clinics. PARTICIPANTS: One hundred and forty-four
      patients referred for treatment of benign voice disorders, 90 undergoing voice
      therapy and 54 undergoing laryngeal microsurgery. MAIN OUTCOME MEASURES: Three
      measures of self-reported voice quality (the vocal performance questionnaire, the
      voice handicap index and the voice symptom scale), plus the short form 36 (SF 36)
      general health status measure and the hospital anxiety and depression score.
      Perceptual, observer-rated analysis of voice quality was performed using the
      grade-roughness-breathiness-asthenia-strain scale. We compared the effect sizes
      (i.e. responsiveness to change) of the principal subscales of all measures before
      and after voice therapy or phonosurgery. RESULTS: All three self-reported voice
      measures had large effect sizes following either voice therapy or surgery.
      Outcomes were similar in both treatment groups. The effect sizes for the observer
      rated grade-roughness-breathiness-asthenia-strain scale scores were smaller,
      although still moderate. The roughness subscale in particular showed little
      change after therapy or surgery. Only small effects were observed in general
      health and mood measures. CONCLUSION: The results suggest that the use of a voice
      specific questionnaire is essential for assessing the effectiveness of voice
      interventions. All three self-reported measures tested were capable of detecting
      change, and scores were highly correlated. On the basis of this evaluation of
      different measures' sensitivities to change, there is no strong evidence to
      favour either the vocal performance questionnaire, the voice handicap index or
      the voice symptom scale.

PMID- 17498326
TI  - Allelic imbalance on chromosomes 3p, 9p and 17p in malignant progression of
      laryngeal mucosa.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the character and significance of
      microsatellite deoxyribonucleic acid allelic imbalance in laryngeal squamous cell
      carcinogenesis. METHODS: We investigated the frequency of expression and clinical
      relationships of loss of heterozygosity and microsatellite instability in 49
      laryngeal premalignant and malignant lesions. Allelic imbalance was analysed
      using six polymorphic markers (D3S1234, D9S171, D9S1748, D9S162, D9SINFA and
      D17S796), via polymerase chain reaction-single sequence length polymorphism
      silver staining. RESULTS: Allelic loss was seen in 3.7 per cent of the six
      markers in hyperplastic lesions, 10.81 per cent in mild dysplasia, 26.03 per cent
      in moderate to severe dysplasia, and 38.67 per cent in laryngeal squamous cell
      carcinoma. Significant associations were found between allelic loss and clinical
      pathological grades (chi2 = 17.686, p = 0.000). No statistically significant
      difference was found in the frequency of microsatellite instability (chi2 =
      0.314, p > 0.05). In the early stages of neoplastic change, the incidence of
      microsatellite instability was higher than that of loss of heterozygosity.
      CONCLUSIONS: Allelic imbalance was associated with the carcinogenesis and
      progression of laryngeal squamous cell carcinoma. Microsatellite analysis might
      provide new approaches to early genetic detection for patients with premalignant
      laryngeal lesions.

PMID- 17498327
TI  - The compliance, true positive and false negative rates of the Charing Cross
      protocol for magnetic resonance imaging screening for cerebellopontine angle
      lesions.
AB  - OBJECTIVES: To assess the effectiveness and determine the compliance to a local
      protocol for requesting magnetic resonance imaging scans to screen for the
      presence of cerebellopontine angle lesions. METHODS: A combined retrospective
      study of all patients who had magnetic resonance imaging scans requested six
      months prior to and one year following introduction of the protocol and
      assessment of the true positive and false negative rate of the protocol by
      assessment of its sensitivity in cases referred from outside the department.
      RESULTS: Comparison of the number of scans in each period showed a reduction in
      annualised rate of 142 to 46. The incidence of positive scans was the same in
      both periods, increasing the true positive rate from 1.4 to 4.3 per cent. The
      false negative rate was 1.1 per cent. CONCLUSIONS: The Charing Cross protocol has
      a good compliance rate within the department, has reduced the cost of screening
      for cerebellopontine angle lesions and has an acceptable true positive and false
      negative rate.

PMID- 17498328
TI  - Cochlear implantation in children with Jervell, Lange-Nielsen syndrome.
AB  - Jervell, Lange-Nielsen syndrome is a condition that causes profound hearing loss
      and disruption of the normal cardiac rhythm. This disorder is a form of long QT
      syndrome, a cardiac disorder that causes the cardiac muscle to take longer than
      usual to recharge between beats. A retrospective case study was performed to
      document cochlear implantation in three profoundly deaf children (two of them
      siblings) with Jervell, Lange-Nielsen syndrome. We discuss diagnosis and
      management of this syndrome and also the long-term performance of cochlear
      implantation in these Iranian patients, referring especially to the role of the
      ENT specialist in diagnosis and treatment. The collected data show that cochlear
      implantation can be relatively safely performed in patients with Jervell, Lange
      Nielsen syndrome and that these children received significant benefit from
      cochlear implantation.

PMID- 17498329
TI  - The Allergic Rhinitis and its Impact on Asthma system: a new classification of
      allergic rhinitis and nasal responsiveness.
AB  - OBJECTIVES AND HYPOTHESIS: Allergic rhinitis has traditionally been classified
      into seasonal and perennial rhinitis. However, many subjects with dual
      sensitisation do not fit neatly into either category. Recently, the Allergic
      Rhinitis and its Impact on Asthma workshop has proposed a new allergic rhinitis
      classification, into intermittent and persistent forms. The purpose of the
      present study was to investigate whether the symptomatic and secretory
      responsiveness of allergic rhinitis sufferers correlated well with the Allergic
      Rhinitis and its Impact on Asthma classification, compared with the traditional
      classification. STUDY DESIGN: Experimental study. METHODS: Forty subjects with
      allergic rhinitis and 13 normal controls underwent a unilateral nasal bradykinin
      challenge protocol. Symptom scores were recorded and secretion weights measured
      bilaterally using filter paper disks. The symptomatic and secretory responses of
      allergic subjects were analysed according to both the traditional and the
      Allergic Rhinitis and its Impact on Asthma classifications, and the two systems
      were compared. RESULTS: For both classification systems, the two groups of
      allergic subjects were clearly demarcated by secretory responses. However, after
      classification according to the traditional system, there was a lack of clear
      demarcation between the groups as regards symptomatic response, whereas clear
      demarcation of symptomatic responses was seen after using the Allergic Rhinitis
      and its Impact on Asthma classification. CONCLUSIONS: In allergic rhinitis
      subjects, the degree of nasal responsiveness was closely related to their
      Allergic Rhinitis and its Impact on Asthma classification. Furthermore, this
      classification was not compromised by the inclusion of subjects with dual
      sensitisation. Thus, the Allergic Rhinitis and its Impact on Asthma
      classification may have advantages for future research studies on allergic
      rhinitis.

PMID- 17498330
TI  - Internal jugular vein thrombosis due to distant malignancies: two case reports
      and literature review.
AB  - The internal jugular vein is an uncommon site of spontaneous venous thrombosis.
      Most cases usually result from intravenous drug abuse, jugular vein
      catheterisation, neck dissection, a hypercoagulable state associated with
      malignancy (Trousseau's syndrome), neck injury or ovarian overstimulation
      syndrome. In this paper, we present and discuss two cases of spontaneous jugular
      vein thrombosis associated with breast and lung malignancies. The possibility of
      Trousseau's syndrome due to distant malignancy should be considered by
      otolaryngologists and appropriately investigated.

PMID- 17498331
TI  - Changes in nasal aesthetics following nasal bone manipulation.
AB  - Nasal bone fractures are the commonest type of bony facial injury causing
      aesthetic deformity. The aim of this study was to identify the effect of nasal
      trauma and fracture manipulation on the aesthetic proportions of the nose, by
      comparing pre- and post-treatment nasal aesthetics. Thirty-two patients (26 men
      and 6 women) underwent aesthetic assessment prior to treatment of the injury by
      closed nasal manipulation, 7 to 10 days after the initial injury. Standard facial
      aesthetic photographic assessments were performed prior to and following
      manipulation. Assessment involved measurement of standard nasal aesthetic
      parameters. In the nasal trauma cohort, the main anomalies in nasal aesthetics
      were nasal deviation and differences in the nasal aesthetic profile. Nasal
      fracture manipulation successfully reduced deviation from an average of 35
      degrees pre-manipulation to an average of 9 degrees post-manipulation.

PMID- 17498332
TI  - Parapharyngeal abscess complicated by endophthalmitis: a rare presentation of
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: We report an extremely rare case of nasopharyngeal carcinoma
      presenting as a lateral neck abscess complicated by endogenous bacterial
      endophthalmitis. Endogenous bacterial endophthalmitis complicating a neck abscess
      has not been reported in the recent English literature. We discuss the possible
      pathophysiology of neck abscess as a presenting feature of nasopharyngeal
      carcinoma, and the relationship between the parapharyngeal abscess and endogenous
      bacterial endophthalmitis. CASE REPORT: A middle-aged Chinese man presented with
      a left neck abscess associated with progressive vision deterioration and
      proptosis of the left eye. Incidentally, his random blood glucose was found to be
      elevated. Nasal endoscopy also revealed bilateral bogginess in the fossa of
      Rosenmuller. A diagnosis of left neck abscess with endogenous endophthalmitis
      associated with underlying diabetes mellitus was made. A computed tomography scan
      of the neck showed a left parapharyngeal abscess. Incision and drainage of the
      abscess together with biopsy of the nasopharynx was performed. Due to the non
      salvageable condition of the left eye, evisceration was also performed. Pus
      culture studies from the neck abscess grew Klebsiella pneumoniae, and
      nasopharyngeal biopsy revealed undifferentiated carcinoma. CONCLUSION:
      Nasopharyngeal carcinoma is endemic in South East Asia and can have multiple,
      varied presentations. Therefore, in this setting, the clinician should have a
      high index of suspicion, especially in a patient from the Chinese ethnic group.

PMID- 17498333
TI  - Stapediovestibular dislocation with pneumolabyrinth.
AB  - Traumatic luxation of the stapes into the vestibule is a rare entity, and the
      disease complicated with pneumolabyrinth is extremely rare. We report the case of
      a 72-year-old woman with pneumolabyrinth associated with a stapediovestibular
      dislocation. The patient presented with vertigo and nystagmus following
      penetrating trauma to the middle ear. High resolution computed tomography scans
      demonstrated air in the vestibule and dislocation of the stapes. Exploratory
      tympanotomy demonstrated oozing of the perilymph from the oval window and
      depression of the stapes into the vestibule. Pneumolabyrinth and stapes luxation
      detected by high resolution computed tomography should be predictive of a
      perilymphatic fistula.

PMID- 17498334
TI  - Dual pathology: cervicofacial actinomycosis and nicorandil-induced oral
      ulceration.
AB  - INTRODUCTION: Oral ulceration has many causes and is a common presenting symptom
      in otolaryngology. CASE REPORT: This article presents an unusual case of dual
      pathology oral ulceration in an elderly patient. Oral malignancy was initially
      suspected, but the history, examination and investigation showed that the oral
      ulceration was caused by actinomycosis infection and by nicorandil use.
      DISCUSSION: Cervicofacial acinomycosis is a rare, suppurative bacterial disease
      in which abscesses can form in the tissues and break through the skin, creating
      pus-discharging lesions. Nicorandil is a potassium channel blocker used in the
      treatment of ischaemic heart disease. It has been recently recognised as a cause
      of persistent ulcerative stomatitis. CONCLUSION: This case highlights the
      importance of a high index of suspicion for unusual and reversible causes of oral
      ulceration, and of dual pathology as a cause. Such vigilance enables early
      recognition and treatment of potentially reversible conditions.

PMID- 17498335
TI  - Malignant triton tumour of the parapharyngeal space: a case arising from the
      cervical sympathetic nerve.
AB  - BACKGROUND: Malignant triton tumour is a relatively rare, aggressive sarcoma
      comprising both malignant schwannoma cells and malignant rhabdomyoblasts.
      Malignant triton tumour of the parapharyngeal space is exceptionally rare, with
      only one case being described in the literature. Malignant triton tumour of the
      cervical sympathetic nerve has not previously been reported. METHODS: We report a
      case involving the parapharyngeal space and arising from the cervical sympathetic
      nerve, and we review the management and outcome of the previous case reported in
      this rare location. CONCLUSIONS: The parapharyngeal space is a unique location.
      Owing to this specific localisation, adjuvant therapy in addition to complete
      resection may be important in the treatment of malignant triton tumour in this
      rare location.

PMID- 17498336
TI  - Cardiovascular hoarseness: an unusual presentation to otolaryngologists.
AB  - OBJECTIVE: We discuss the case of a 73-year-old woman with a six-month history of
      hoarseness secondary to an aortic arch pseudoaneurysm. METHOD: We present the
      findings of an extensive review of the literature relating to cardiovascular
      disorders involving the recurrent laryngeal nerve (i.e. Ortner's syndrome).
      RESULTS: Ortner's syndrome, also known as cardiovocal syndrome, is a rare
      condition, with few reports in the literature. CONCLUSION: This is only the
      second documented case of Ortner's syndrome in Great Britain and Ireland, and the
      first demonstrating an aortic pseudoaneurysm.

PMID- 17498337
TI  - Laryngotracheal augmentation using titanium mesh.
AB  - BACKGROUND: The management of laryngotracheal stenosis is still a serious
      surgical challenge. The fact that there are currently numerous reconstruction
      procedures indicates that there is at present no standard treatment. STUDY
      DESIGN: Titanium mesh was used instead of traditional homografts in
      reconstruction of the anterior laryngotracheal wall in 12 tracheostomised
      patients with benign chronic laryngotracheal stenosis. The anterior
      laryngotracheal wall was split, followed by excision of scar tissue and fixation
      of the titanium plate at the split end. A Silastic stent was inserted above the
      tracheostomy tube and fixed in place by running sutures fixed to the skin by
      buttons. The stent was removed endoscopically six weeks later and a trial of
      decannulation was undertaken. RESULTS: Endoscopically, good epithelisation was
      seen on the inner surface of the mesh in 10 cases and decannulation was possible.
      Four of these patients required endoscopic debulking of granulation tissue.
      Decannulation was impossible in two cases, one due to excessive granulation
      tissue and the other due to prolapse of the titanium mesh into the tracheal lumen
      (the mesh was removed endoscopically and a Montgomery T-tube inserted).
      CONCLUSION: Titanium mesh was found to be a good alternative for augmentation of
      the anterior laryngotracheal wall. It offered rigid support, with fewer of the
      complications reported with other grafts.

PMID- 17498338
TI  - Intracorporeal electrokinetic lithotripsy: an advancement in minimally invasive
      management of parotid duct calculus.
AB  - BACKGROUND: Symptomatic salivary stones in the middle or proximal parotid duct
      have previously been treated by gland excision, which is associated with a 3-7
      per cent risk to the facial nerve. Minimally invasive approaches to the
      management of salivary duct calculi have been devised over the past decade.
      Fluoroscopically guided basket retrieval, lithotripsy and intra-oral stone
      removal under general anaesthesia have found favour with most surgeons.
      Endoscopically controlled intracorporeal shock wave lithotripsy using the
      pneumoblastic lithotripter has been replaced by electrohydraulic lithotripsy
      (used in sialolith treatment). METHOD: The electrokinetic lithotripter is
      normally used for the treatment of lower ureteric stones, and has the benefit of
      minimal concomitant tissue damage. We have extended its use to the treatment of
      parotid duct calculi. We present initial results for its use in the treatment of
      a proximal parotid duct stone. RESULT: Application of the shock wave to the stone
      under direct vision avoided injury to the duct or to any local structure. The
      patient made an uneventful recovery and was asymptomatic after 18 months' follow
      up. CONCLUSION: Continuous, endoscopically monitored electrokinetic lithotripsy
      with good irrigation gives a well illuminated field and absolute delivery of
      energy to the target. It avoids the side effects caused by impact of the shock
      wave on the parotid duct and adjacent anatomical structures, thereby making it a
      safer procedure.

PMID- 17498339
TI  - Primitive neuroectodermal tumour of the tongue.
AB  - Peripheral primitive neuroectodermal tumours, which belong to the Ewing sarcoma
      tumour family, are extremely rare. These tumours are highly aggressive and are
      known to have a poor prognosis. Immunostaining with at least two neural markers
      and evidence of an abnormal t(11;22)(q24;q12) translocation are hallmark features
      in this diagnosis. We present the first reported case of peripheral primitive
      neuroectodermal tumour to occur in the tongue.

PMID- 17498340
TI  - [Occupational exposure induced human transmissible highly pathogenic H5N1 avian
      influenza in one patient].
AB  - OBJECTIVE: To describe the clinical manifestations and lung imaging
      characteristics of the human transmissible highly pathogenic H5N1 avian
      influenza. METHODS: The clinical manifestations and lung imaging characteristics
      of human transmissible highly pathogenic H5N1 avian influenza in one patient were
      reviewed and analyzed. RESULTS: The patient had the clear history of occupational
      exposure. The fever and symptoms of influenza were prominent at onset and
      associated with the symptoms of the digestive tract. The laboratory findings
      comprised the significant decrease of the white blood cell count and the
      lymphocyte number and the impairment of the liver function and the myocardial
      enzymes. The disease progressed rapidly and multiple organs including lung,
      heart, liver and kidneys were involved. It was ineffective to administer anti
      fungal, anti-virus and anti-inflammation medicines. It was in vain to use
      mechanical ventilation and pneumothorax intubation and closed drainage as well as
      the support therapy. In the X-ray film, the lesions progressed quickly and
      changed diversely with absorption and development at the same time. The nasal and
      throat swabs and the gargle specimen were detected with RT-PCR and real time PCR
      by Chinese Center for Disease Control and Prevention. The results showed that
      both the specific HA and NA genes of the avian influenza virus H5N1 subtype were
      positive and in the same time a strain of avian influenza virus
      A/jiangxi/1/2005H5N1) was separated and obtained from the nasal and throat swabs.
      The autopsy showed that diffuse injury of alveolus in lungs, DIC and multiple
      organ injury. CONCLUSION: The human transmissible highly pathogenic H5N1 avian
      influenza is a lethal disease. The disease progresses rapidly with the absorption
      and development at the same time in the lungs and unfortunately there are no
      effective therapeutic measures. The prevention of the contagious disease for the
      occupationally exposed population should be emphasized.

PMID- 17498341
TI  - [Detection of fungi in liquor workers with tinea corporis and tinea cruris using
      arbitrarily primed polymerase chain reaction].
AB  - OBJECTIVE: To explore the method of rapid detection of skin fungi and the
      significance of conventional diagnosis liquor worker tinea corporis and tinea
      cruris using arbitrarily primed polymerase chain reaction AP-PCR. METHODS: Among
      liquor workers who were 50 tinea corporis patients, 58 tinea cruris patients and
      50 health persons, we amplified the DNAs of the dermatophytes were amplified
      using AP-PCR and random primers OPD18 5'-GAGAGCCAAC-3' and OPAA11 5'-ACCCGACCTG
      3', at the same time, the dermatophytes with microscope were detected and
      cultured. RESULTS: AP-PCR analysis detected fungal DNA in 45 patients(90.00%)
      among 50 liquor worker patients with tinea corporis, 31 patients(62.00%) had the
      positive results of microscope detection, and 41 patients(82.00%) had the
      positive results of standard culture. Among these workers who suffered from tinea
      corporis, T.rubrum, T.mentagrophyte, M. canis and E.floccosum were detected by AP
      PCR. T.rubrum, T.mentagrophyte and M.canis were detected by standard culture. AP
      PCR analysis detected fungal DNA in 53 patients(91.38%) among 58 liquor worker
      patients with tinea cruris, 37 patients(63.79%) had the positive results of
      microscope detection, and 48(82.76%) had the positive results of standard
      culture. Among the 58 workers who had tinea cruris, T.rubrum, E.floccosum and
      T.mentagrophyte were detected by AP-PCR and standard culture. Among 50 health
      persons, AP-PCR analysis detected fungal DNA in 3 persons(6.00%). The detection
      result with AP-PCR indicated that the kinds of fungi were T.rubrum and
      T.mentagrophyte. No one health person had the positive result in detection of
      fungi using microscope detection. Only one(2.00%) health person was detected to
      be infected by fungus with cultural way. The kind of fungus was T.rubrum.
      CONCLUSION: AP-PCR is a rapid, sensitive and specific detection method for
      occupational dermatophyte patients. It can be used to detect and diagnose
      professional dermatophytosis.

PMID- 17498342
TI  - [Utilizing 2-DE and MALDI-TOF MS/MS to screen differentially expressed serum
      proteins of silicosis].
AB  - OBJECTIVE: To establish 2-dimensional gel electrophoresis (2-DE) images and seek
      differentially expressed serum proteins for understanding the pathogenesis of
      silicosis. METHODS: 2-DE and matrix-assisted laser desorption/ionization time of
      flight tandem mass spectrometry (MALDI-TOF-MS/MS) were used to screen
      differentially expressed serum proteins among silica-exposed population, suspect
      of silicosis (0+), phase one (I) group with silicosis and control group(non
      silica exposure). RESULTS: Complement C4, leucine-rich alpha-2-glycoprotein and
      alpha-1-antitrypsin were significantly highly expressed in suspect of silicosis
      (0+) group(P < 0.01), but lowly in other groups. Inversely, serotransferrin was
      significantly down-regulated only in suspect of silicosis (0+) group(P < 0.01).
      Plasma glutathione peroxidase, tetranectin, apolipoprotein A-I and transthyretin
      were equally expressed in the serum of control group and silica-exposed
      population group, but decreased in the suspect of silicosis (0+) and phase (I)
      group. CONCLUSION: Complement C4, leucine-rich alpha-2-glycoprotein, alpha-1
      antitrypsin, serotransferrin, plasma glutathione peroxidase, tetranectin,
      apolipoprotein A-I and transthyretin are differentially expressed in the silica
      exposed group and phase (I) group with silicosis, and the result should be
      validated by other biochemical technologies.

PMID- 17498344
TI  - [Effects of PBDE-47 on oxidative stress and apoptosis in SH-SY5Y cell].
AB  - OBJECTIVE: To investigate the oxidative stress and apoptosis induced by 2, 2', 4,
      4'-polybrominated diphenyl ethers (PBDE-47) in human neuroblastoma SH-SY5Y cells,
      and to explore the involved role of reactive oxygen species (ROS) on apoptosis.
      METHODS: The rate of cellular survivors, intracellular ROS level, malondialdehyde
      (MDA) content and percentage of apoptosis were measured respectively after the SH
      SY5Y cell were exposed to 2, 4, 8 microg/ml PBDE-47 for 24 h in vitro. RESULTS:
      The rate of cellular survivors in the low dose PBDE-47-treated group was higher
      than the control group (P < 0.05), but the moderate and high dose PBDE-47-treated
      groups were significantly lower than the control group (P < 0.05). The MDA
      contents in the moderate and high dose PBDE-47-treated groups were significantly
      higher than the control group (P < 0.05) and increased with increase of PBDE-47
      exposure concentrations. Compared with the control group, the levels of ROS were
      significantly increased with increase of PBDE-47 concentrations (P < 0.05). In
      the moderate and high dose PBDE-47-treated groups, the percentages of apoptosis
      were significantly higher than that of the control group (P < 0.05). CONCLUSION:
      PBDE-47 can induce oxidative stress and apoptosis in SH-SY5Y cell. ROS may play
      an important role in the apoptosis induced by PBDE-47.

PMID- 17498343
TI  - [Relationship between occupational stress and blood glucose, blood lipid, blood
      pressure of video display terminal operators].
AB  - OBJECTIVE: To explore the relationship between occupational stress and blood
      glucose, Blood lipid and blood pressure. METHODS: 108 video display
      terminals(VDT) operators who had the working experience were recruited to the
      study. The occupational stress indicator (OSI), the lever of blood glucose,
      cholesterol, triglyceride, lipoprotein of high density and lipoprotein of low
      density in serum were measured by using GOD-PAP, CHOD-PAP, GPO-PAP and PVS. The
      subjects were classified into three groups according to the score of occupational
      stress. RESULTS: The contents of blood glucose of low, middle and high level of
      stress groups were (3.39 +/- 1.24), (3.59 +/- 1.26), (2.54 +/- 0.94) mmol/L
      respectively (F = 7.324, P < 0.01), and with the increase of level of stress, the
      content of blood glucose decreased significantly (r = -0.376, P < 0.01).
      CONCLUSION: The level of blood glucose of VDT operators is affected by
      occupational stress, among video display terminals and it can be used as the
      index for estimating occupational stress.

PMID- 17498345
TI  - [Alterations of microtubule and microfilament expression in spinal cord of carbon
      disulfide intoxicated rats].
AB  - OBJECTIVE: To investigate whether the alterations of microtubule and
      microfilament expression are responsible for the neurotoxicity of carbon
      disulfide. METHODS: Wistar rats were administered with carbon disulfide by gavage
      at a dosage of 300 or 500 mg/kg for continuous 12 weeks (five times per week).
      Spinal cords of carbon disulfide-intoxicated rats and their age-matched controls
      were Triton-extracted and ultracentrifuged to yield a pellet and a corresponding
      supernatant fraction. Then, the contents of alpha-tubulin, beta-tubulin, and beta
      actin in both fractions were determined by immunoblotting. In the meantime, their
      mRNA levels in spinal cords were quantified using reverse transcriptase
      polymerase chain reaction (RT-PCR). RESULTS: In the supernatant fraction, the
      contents of beta-tubulin and beta-actin in both treated groups increased
      significantly (P < 0.01) the content of beta-tubulin increased by 141% and 158%
      respectively, and the content of beta-actin increased by 19% and 32%
      respectively. In the pellet fraction, the content of beta-tubulin in both groups
      increased by 107%(P < 0.01) and 118%(P < 0.01) respectively, and the others keep
      unaffected. In the meantime, the levels of of mRNA expression of beta-tubulin and
      beta-actin gene were elevated consistently in CS(2)-treated groups (P < 0.01) the
      levels of mRNA expression of beta-tubulin increased by 207% and 212%
      respectively, and the levels of mRNA expression of beta-actin increased by 94%
      and 91% respectively. CONCLUSION: Carbon disulfide intoxication results in
      alternations of microtubule and microfilament expression, and the alternations
      might be related to its neurotoxicity.

PMID- 17498346
TI  - [Involvement of Caspase-3 and p38 mitogen-activated protein kinase in MMT-induced
      apoptosis in PC-3M cells].
AB  - OBJECTIVE: To explore the function of Caspase-3 and p38 MAPK in MMT-induced
      apoptosis in PC-3M cells. METHODS: After incubation of PC-3M cells with 1 mmol/L
      MMT, the activity of Caspase-3 was examined. The influence on cells viability of
      Z-DEVD-FMK, a Caspase-3-specific peptide inhibitor, was also examined. Western
      blot was used to examine the change of p38 MAPK. The effect on cells viability
      and Caspase-3 activity of SB203580, a specific inhibitor of p38 MAPK, were also
      examined. RESULTS: The activity of Caspase-3 increased significantly in MMT
      induced apoptosis in PC-3M cells /9P < 0.01), and Z-DEVD-FMK could protect cells
      from apoptosis (P < 0.01). In this course, the phosphorylation of p38 MAPK could
      be observed. SB203580 inhibited Caspase-3 activity (P < 0.05) and prevented PC-3M
      cells from MMT-induced apoptosis (P < 0.05). CONCLUSION: Caspase-3 and p38 MAPK
      are involved in MMT-induced PC-3M cells apoptosis.

PMID- 17498347
TI  - [Protective effect of melatonin on oxidative damage by deltamethrin in rat
      brain].
AB  - OBJECTIVE: To study the potential protective effect of melatonin on the oxidative
      damage induced by deltamethrin in cerebral cortex, hippocampus and cerebellum of
      rats. METHODS: 35 male wistar rats were randomly divided into five groups(seven
      rats per group): olive oil control, deltamethrin-treated (12.5 mg/kg),
      melatonin(25.0 mg/kg) and deltamethrin plus melatonin (25.0 mg/kg , 2.5 mg/kg
      respectively) group. Levels of malondialdehyde (MDA) and the activity of
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px),
      glutathione (GSH) in cerebral cortex, hippocampus and cerebellum were determined
      after 5 days of DM treatments. RESULTS: MDA content in cerebral cortex,
      hippocampus and cerebellum tissue of the DM-treated rats were significantly
      higher than those in control group, and compared with DM-treated group, MDA
      content in those tissue of MT + DM-treated group have significantly decreased
      after 5 days of DM exposure (P < 0.05). Activities of GSH-Px in DM-treated group
      were significantly lower than those in control group, and those in the MT + DM
      group were significantly higher than DM group(P < 0.05). CONCLUSION: DM can
      induce the oxidative damage in rat brain and melatonin has protective effects on
      deltamethrin-induced oxidative damage in hippocampus, cerebral cortex and
      cerebellum of rats.

PMID- 17498348
TI  - [Neurobehavioral function status of ten-thousand-ton train drivers].

PMID- 17498349
TI  - [Four patients with acute ethylene glycol poisoning].

PMID- 17498350
TI  - [5-nitro-toluidine induced subacute poisoning hepatopathy in 3 patients].

PMID- 17498351
TI  - [Emergency treatment and nursing for patients with acute triphosgene poisoning].

PMID- 17498352
TI  - [Red blood cell parameters of patients with coal workers' pneumoconiosis].

PMID- 17498353
TI  - [Present status of occupational hygiene technology service in China].

PMID- 17498355
TI  - [Discussion of several problems in hand-arm vibration disease.].

PMID- 17498354
TI  - [Application of finger dermal temperature and cold water load tests in research
      of occupational hazards of hand-arm vibration.].

PMID- 17498356
TI  - [Several problems in diagnosis of occupational diseases.].

PMID- 17498357
TI  - [Research advance of genotoxicity and carcinogenicity of acrylonitrile].

PMID- 17498360
TI  - [A strategy for preventing pneumoconiosis].

PMID- 17498361
TI  - [Coal workers' pneumoconiosis and silicosis--the South African experience].

PMID- 17498362
TI  - [Investigation of hydrogen sulfide poisoning accidents caused by manipulations
      against rules and regulations].

PMID- 17498363
TI  - [High performance liquid chromatography for determination of acetamiprid in
      serum].

PMID- 17498364
TI  - [Management of complicated and persistent bleeding during operation].

PMID- 17498365
TI  - [Management and its criterion of iatrogenic blood vessel injuries].

PMID- 17498366
TI  - [Application of vascular surgery techniques in neck surgery].

PMID- 17498367
TI  - [Application of vascular surgery techniques in organ transplantation].

PMID- 17498368
TI  - [Application of vascular surgery techniques in trauma of extremities].

PMID- 17498369
TI  - [Application of vascular surgery techniques in retroperitoneal tumors].

PMID- 17498370
TI  - [Application of vascular surgery techniques in tumor resection].

PMID- 17498371
TI  - [Vascular surgical management of intravenous leiomyomatosis].

PMID- 17498373
TI  - [Pay more attention to differential diagnosis of vascular and neurogenic
      intermittent claudication].

PMID- 17498374
TI  - [Endovascular stent-graft treatment for DeBakey I aortic dissection].
AB  - OBJECTIVE: To study endovascular treatment of DeBakey type I aortic dissecting
      aneurysm. METHODS: Seven patients with DeBakey I aortic dissecting aneurysms were
      treated. Diagnoses were confirmed by MRA, CT and angiography. The intimal tear
      entry was in the ascending aorta, 2.5 approximately 6.0 cm from the ostia of the
      coronary arteries, and 0.5 approximately 4.0 cm from the brachiocephalic trunk
      opening. Endovascular stent-grafts were deployed via a left common carotid artery
      (LCCA) approach in 2 cases and right femoral artery (RFA) approach in 5 cases.
      Prior to treatment, a left subclavicular artery (LSA)-LCCA shunt was established
      to ensure blood supply to the LCCA during surgery in 2 cases via LCCA approach,
      and a LSA-LCCA-right common carotid artery (RCCA) synthetic bypass was
      established to ensure blood supply to the brain in 2 cases in RFA approach.
      RESULTS: The operative success rate was 100%. In 3 cases, endoleak persisted
      after the first stent was placed, but this was eliminated by placement of a
      second stent. All patients survived except one who died of acute massive
      hemorrhage from the upper gastrointestinal tract one month postoperatively. The
      false lumen in all 6 cases became thrombosed and no endoleak or new aortic
      dissecting aneurysms developed. CONCLUSIONS: Endovascular treatment of DeBakey
      type I aortic dissecting aneurysm is feasible, minimally invasive, and effective.
      Case selection depends on the distance of the coronary artery ostia from the tear
      entry.

PMID- 17498375
TI  - [Clinical analysis of vascular reconstruction in 56 cases of lower extremity
      ischemia suffering from infrapopliteal arterial occlusion].
AB  - OBJECTIVE: To summarize therapeutic efficacy of vascular reconstruction in
      treating infrapopliteal arterial occlusion. METHODS: Retrospective analysis of
      vascular reconstruction of lower extremity was made in 56 cases suffering from
      popliteal arteries or 3 branches of popliteal arteries (anterior tibial,
      posterior tibial, peroneal artery) between July 2001 and August 2005 in our
      hospital. According to the level of lower extremity arterial occlusion, a
      composite grafts which consisting of a combined proximal PTFE prosthesis grafts
      with autogenous vein grafts were used to establish the sequential vascular
      reconstruction for multilevel and multistage arterial occlusive disease. RESULTS:
      The mean follow-up period after operation was 17 months. The primary graft
      patency rates in this series was 67.3%, the secondary graft patency rate was
      78.8%. CONCLUSIONS: The treatment of composite sequential bypass is a practical
      means for multilevel arterial occlusive disease suffering from femoral
      infrapopliteal arteries, which effectively resolves the insufficiency supply of
      autogenous vessel grafts and the problem of bad patency rate for vascular
      reconstruction with prosthetic grafts alone in arterial occlusion suffering from
      infrapopliteal arteries.

PMID- 17498376
TI  - [Treatment of left subclavian artery in endovascular repair of thoracic aortic
      aneurysm and thoracic aortic dissection].
AB  - OBJECTIVE: To investigate the treatments of left subclavian artery (LSA) in
      endovascular repair (EVR) of thoracic aortic aneurysm (TAA) and thoracic aortic
      dissection (TAD). METHODS: In 54 TAD or TAA cases, all of the proximal landing
      zone (PLZ) were less than 15 mm and only the LSA was needed to be treated in EVR,
      the following methods and techniques were used in the treatments of LSA: complete
      cover, partial cover, endovascular reconstruction following complete cover,
      surgical reconstruction before complete cover. RESULTS: DSA was used to evaluate
      the condition of cerebral circulation in all cases. Forty left subclavian
      arteries were covered completely. Ten were covered completely after right
      subclavian artery (RSA)-LSA or left common carotid artery (LCCA)-LSA bypass. PTA
      and stent in LSA was done in 3 cases. In 1 case, LSA was covered completely
      first, and then the graft was punctured and bare stent was fixed after inflation
      by cutting balloon. All of the ancillary techniques were enforced successfully.
      No severe complications were found in brain and upper extremity. The proximal
      endoleak rate was 17% (9/54). In the 40 cases whose LSA were not reconstructed,
      the primary left subclavian steal syndrome (LSSS) happened in 8 cases (20%) and
      the primary average systolic pressure of left brachial artery was 63 +/- 24 mm
      Hg. CONCLUSIONS: EVR can be enforced safely and efficiently in TAA and TAD with
      short PLZ by some ancillary endovascular or surgical techniques. The methods to
      treat the LSA depend on the condition of the cerebral circulation.

PMID- 17498377
TI  - [Diagnosis and treatment of asymptomatic aortic dissection].
AB  - OBJECTIVE: To summarize the diagnostic and therapeutic methods of asymptomatic
      aortic dissection (AD). METHODS: Ten patients of asymptomatic AD were treated
      from January 2002 to June 2006. The patients were followed up and their data were
      reviewed retrospectively. RESULTS: Two patients of type A AD treated by open
      surgery and the 6 patients of type B AD received endovascular stent-graft repair
      were successfully treated, and no in-hospital death and severe complication
      occurred. Furthermore, all of them survived during follow-up. One of the 2
      patients of type B AD received medical treatment still survive, but the other
      suddenly died during follow-up. The most possible cause of his death was fatal
      aorta rupture. CONCLUSIONS: The diagnosis of asymptomatic AD could be missed or
      mistaken easily because of its asymptomatic. Keeping a high clinical index of
      suspicion is crucial in establishing the diagnosis of asymptomatic AD. The
      asymptomatic AD also has high risk of fatal aorta rupture associated with re
      dissection and aneurysmal dilatation. Therefore, type A and B asymptomatic AD
      should be treated by open surgery or endovascular repair respectively if
      possible. Endovascular stent-graft repair is a safe and effective method for the
      treatment of type B asymptomatic AD.

PMID- 17498378
TI  - [Selection of the initial surgery extent for differentiated thyroid cancer
      without metastasis].
AB  - OBJECTIVE: To discuss the selection of the initial surgery extent for
      differentiated thyroid cancer (DTC) without metastasis. METHODS: The clinical
      data of 504 cases with DTC, who accepted the surgical treatment from Jan 1995 to
      Dec 2004, were analyzed and studied. There were 329 cases without metastasis. The
      operative extents less than total thyroidectomy were performed on 93 cases
      (92.1%) with stage T(1), 166 cases (88.3%) with stage T(2), 22 cases (91.7%) with
      stage T(3) and 12 cases (75.0%) with stage T(4). The recurrence situation after
      the initial surgery was compared between different T-stage groups and between
      different surgical extents, total and less than total thyroidectomy. RESULTS: The
      recurrence of DTC was found in 37 cases of the follow-up cases (8.9%), including
      29 cases without metastasis in the initial surgery. There was no significant
      difference in the recurrent rate between T(1) and T(2) groups (P>0.05). The
      significant difference was found in recurrent rate between T(1) and T(3) or T(4)
      groups, T(2) and T(3) or T(4) groups (P<0.05). No significant difference in the
      ratio of the initial surgical extent less than total thyroidectomy was found
      between stage T(1) and T(2) cases without metastasis (P>0.05). The rate of the
      recurrent laryngeal nerve injury was 1.2%. The transient hypoparathyroidism
      happened in 2% of the cases, without the permanent hypoparathyroidism.
      CONCLUSIONS: The surgical extent less than total thyroidectomy, especially
      subtotal thyroidectomy, is rational and available to stage T(1) and T(2) cases of
      DTC without metastasis. It can effectively remove the tumor and avoid
      postoperative complications. Total thyroidectomy should be performed on stage
      T(3) and T(4) cases of DTC.

PMID- 17498379
TI  - [Study of bloodless hepatectomy under occlusion of total hemi-hepatic vessel].
AB  - OBJECTIVE: To explore the preliminary clinical evaluation of hepatectomy with
      total hemi-hepatic vascular exclusion. METHODS: Twenty-eight patients with
      primary liver cancer were divided into two groups of hepatectomy with total hemi
      hepatic vascular exclusion (group A) and total hepatic inflow occlusion (group
      B). The time of hepatic vascular control, intraoperative blood loss, volume of
      removed liver, postoperative liver function recovery and complications were
      compared between the two groups. RESULTS: The intraoperative blood loss in group
      A was (296 +/- 240) ml, which was less significantly than that in group B [(582
      +/- 497) ml] (P<0.05). The serum pre-albumin levels on the day 1, 3 and 7 after
      operation in group A were (164 +/- 39) mg/L, (111 +/- 17) mg/L and (104 +/- 23)
      mg/L, which were higher significantly than that in group B [(134 +/- 34) mg/L,
      (90 +/- 22) mg/L and (82 +/- 35) mg/L] (P<0.05). While the time of hepatic
      vascular control and volume of lost liver were no difference between the groups
      (P>0.05). There were no significant difference in other items between the groups.
      CONCLUSIONS: Intraoperative blood loss and liver damage of hepatectomy under the
      total hemi-hepatic vascular exclusion could be less than that under the other
      methods of vascular occlusion. It could be worth improving and applying further.

PMID- 17498380
TI  - [Clinical evaluation of laparoscopic common bile duct exploration in 587 cases].
AB  - OBJECTIVE: To summarize the experience of laparoscopic common bile duct
      exploration. METHODS: The clinical data of 587 cases who underwent laparoscopic
      common bile duct exploration from June 1992 to May 2006 were analyzed. RESULTS:
      The surgery was successful in 585 cases (99.7%), 2 cases were converted to open
      common bile duct exploration. The duration of operation was 60 approximately 230
      min (averaged 85 min), the complications consisted of biliary fistula (n=13),
      injury of the duodenum (n=1), abscess of drainage tube orifice (n=1), titanium
      clip discharging out from T tube (n=3), residual common bile duct stones (n=35).
      The patients could take food and walk on the second postoperative day and average
      postoperative hospital stay was 4.6 days. CONCLUSIONS: Laparoscopic common bile
      duct exploration is a safe and effective procedure in treating the calculus of
      bile duct.

PMID- 17498381
TI  - [Study on lymph node metastasis in 292 patients with early gastric cancer].
AB  - OBJECTIVE: To evaluate the status of lymph node metastasis (LNM) and reasonable
      procedure in early gastric cancer (EGC). METHODS: Two hundred and ninety-two
      patients with histologically proven mucosal or submucosal gastric cancer who
      underwent gastrectomy/lymphadenectomy were included in this study. The numbers of
      total dissected lymph node were all above 15 in all patients. The clinical
      characteristics, pathologic features, and LNM were assessed by univariate and
      multivariate analysis. RESULTS: LNM were observed in 43 of 292 cases (14.7%), and
      6.4% in mucosal lesions and 22.4% in submucosal lesions. The LNM was identified
      in 12.7% at the first level, 7.2% at the second level and 0.34% at the third
      level. The LNM frequency was found in the 6, 3, 4, 1, 5 lymph node (from high to
      low) consequently at the first level and the 7, 8a lymph node at the second
      level. The EGC with nodal involvement and the tumors < 2.0 cm in diameter were
      all depressed type. The diameter of elevated type with LNM was no less than 3.0
      cm in this series. The depth of invasion and lymphatic vessel involvement were
      independent influencing factors in LNM on multivariate analysis (P<0.05).
      CONCLUSIONS: Less extensive surgery might be considered for the elevated type
      EGC, and tumors <or= 2.0 cm in diameter and mucosal lesions. Gastrectomy with D1
      plus No.7, 8a lymphadenectomy might be carried out in the depressed type/<or= 3.0
      cm in diameter, or in the elevated type/> 3.0 cm in diameter. With respect to the
      depressed type EGC/tumors > 3.0 cm in diameter, gastrectomy with D2
      lymphadenectomy is proper.

PMID- 17498382
TI  - [Protective effects of vasoactive intestinal peptide on septic shock rats].
AB  - OBJECTIVE: To investigate the protective effects of vasoactive intestinal peptide
      (VIP) on septic shock rats and explore its possible mechanism. METHODS: Cecal
      ligation and puncture (CLP) was performed to produce septic shock rat model.
      Thirty adult Sprague-dawley rats were randomly divided into 3 groups with 10
      animals in each group: sham operation group, CLP group and VIP group. The rats in
      VIP group were given intravenous injection of VIP (5 nmol per rat) instantly
      after the CLP operation. Then the mean arterial pressure (MAP) was monitored
      consistently and survival rate was observed. Blood samples were obtained from
      femoral artery for measuring the serum concentrations of tumor necrosis factor
      alpha (TNF-alpha) and interleukin-10 (IL-10) by using enzyme-linked immunosorbent
      assays (ELISA). Organs (lung, kidney and intestine) were harvested for
      pathological examination. RESULTS: At each time point after 8 h, the MAP of VIP
      rats was significantly higher than that in CLP rats (P<0.05). In VIP group rats,
      the serum TNF-alpha concentration was decreased meanwhile IL-10 level was
      increased with markedly alleviated organic pathological injuries and the survival
      rate was obviously raised. CONCLUSIONS: VIP exerts protective effects on septic
      shock rats through inhibiting production of proinflammatory factors and
      stimulating the production of anti-inflammatory cytokines.

PMID- 17498383
TI  - [A selection of methods for immediate and delayed breast reconstruction].
AB  - OBJECTIVE: To investigate the surgical methods, indications and effects of
      postmastectomy breast reconstruction in 67 consecutive patients. METHODS: From
      July 2002 to October 2005, 67 patients received postmastectomy breast
      reconstructions. Immediate breast reconstructions were performed using full-size
      implants in 38 cases, Becker expandable implants in 16 cases, unilateral pedicled
      transverse rectus of abdominis musculocutaneous (TRAM) in 2 cases. Delayed breast
      reconstruction were carried out in 6 cases with unilateral pedicled TRAM flaps, 4
      cases with extended latissimus dorsi musculocutaneous flap (ELDF), one case with
      Becker expandable implant. RESULTS: Of the patients, more than 90% were satisfied
      with the results. Minor complications were recorded in 5 patients, including
      small local skin necrosis, partial necrosis of nipple-areola complex preserved
      and seroma formation. CONCLUSIONS: Full-size implant breast reconstruction is
      ideal for slender, small-breast women undergoing immediate breast reconstruction
      after skin-sparing mastectomy, but not suitable for delayed breast
      reconstruction. Expandable implants can be used for immediate breast
      reconstruction in patients with large breast or those who received modified
      mastectomy and also can be used for delayed breast reconstruction in patients
      with well-preserved skin and muscle. TRAM or ELDF flap for breast reconstruction
      is a useful procedure with advantages of autologous tissue and excellent results,
      both are suitable for immediate and delayed breast reconstruction.

PMID- 17498384
TI  - [Effects of mouse NIH3T3 cells transfected with VEGF gene on neovascularization
      of ischemic flaps].
AB  - OBJECTIVE: To investigate the feasibility of applying NIH3T3 cells transfected by
      VEGF gene to the treatment of ischemic random skin flaps. METHODS: Plasmid
      PcDNA3.1(-)/VEGF(165) containing VEGF gene was transduced into the mouse NIH3T3
      cells by liposome. Immunohistochemistry was used to detect the expression of VEGF
      protein of mouse NIH/3T3 cells in vitro. The NIH3T3 cells were stained with CM
      DiI before the transplantation. Thirty mice were randomized into 3 groups: Groups
      A, B and C, and were respectively injected with NIH/3T3 cells transfected with
      PcDNA3.1(-)/VEGF(165) plasmid, NIH/3T3 cells and medium only. On the 4th day
      after the injection, random dorsal skin flaps with an area of 4.0 cm x 1.5 cm
      were established. The survival, neovascularization and blood flow recovery of the
      flaps were detected. RESULTS: VEGF-transduced NIH3T3 cells expressed VEGF highly
      in vitro and in vivo. The results showed that flap survival rate in group A
      (95.1% +/- 3.1%) was significantly higher than those in group B (37.4% +/- 6.3%)
      and group C (26.2% +/- 5.6%). The capillary density and the blood perfusion of
      the flaps in group A were significantly higher than those in other two groups.
      CONCLUSIONS: VEGF-transfected NIH3T3 cells can improve ischemic flap
      neovascularization and extend survival areas.

PMID- 17498385
TI  - [Laparoscopic high ligation of hernia sac and median umbilical fold covering
      internal ring in treating pediatric indirect inguinal hernia].
AB  - OBJECTIVE: To investigate the effect and clinic practice of laparoscopic high
      ligation of hernia sac and median umbilicus fold covering internal ring in
      pediatric indirect inguinal hernia. METHODS: Five hundred and fifty-two children
      with indirect inguinal hernia were randomly divided into group A (control group)
      and group B (combination group) according to their check-in dates (odd or even).
      In group A, 275 children were treated with laparoscopic high ligation of hernia
      sac. In group B, 277 children were treated with laparoscopic high ligation of
      hernia sac and suturing the median umbilical fold to internal ring. RESULTS: The
      operation was successfully performed in all 552 patients. The operating time in
      group A and B were (12.3 +/- 5.5) min and (20.6 +/- 4.2) min (P<0.05)
      respectively; and the hospital stay were (2.2 +/- 1.5) d and (2.4 +/- 1.3) d
      (P>0.05); the day of restoring normal active were (1.2 +/- 0.5) d and (1.3 +/-
      0.6) d (P>0.05); the recurrence rate were 2.2% (6/275) and 0 (0/277) (P<0.05). No
      complications, such as abdominal cavity infection and scrotum hematoma occurred
      during the follow-up of 22 months to 55 months. CONCLUSIONS: Laparoscopic high
      ligation of hernia sac and median umbilical fold covering internal ring is safe
      and effective in treating indirect inguinal hernia of the children.

PMID- 17498386
TI  - [Effects of blocking the CXC chemokine receptor 3 pathway on acute rejection of
      islet allograft].
AB  - OBJECTIVE: To identify the effect of PNA CXCR3 on acute rejection of islet
      allograft. METHODS: The mice islet transplant models were used. The mice were
      divided into three groups including saline group, PNA CXCR3 group and mismatch
      PNA group. In vitro the proliferation capability of T cell was assessed by
      proliferative responses. RT-PCR and western blot were used to detect the
      expression of mRNA and protein. Flow cytometry was applied to determine the
      expression level of CXCR3 in spleen CD3(+) T cells. RESULTS: Compared with saline
      [(6.72 +/- 1.48) d] and PNA mismatch-treated recipients [(6.54 +/- 0.86) d], PNA
      CXCR3-treated recipients demonstrated statistically significant prolongation
      [(9.70 +/- 1.57) d] in functional allograft survival. The CXCR3 mRNA expression
      level of PNA CXCR3 group (1.06 +/- 0.07) was significantly down-regulated
      compared with saline (1.98 +/- 0.22) and PNA mismatch (1.87 +/- 0.10) group at
      the 7th day after transplant. The date showed that CXCR3 protein and lymphocytes
      proliferation capability was significantly down-regulated in PNA CXCR3 group
      compared with saline and PNA mismatch group (P<0.01). CONCLUSIONS: The present
      study indicates that PNA CXCR3 can inhibit T cell activating and prolonging the
      survival time of islet allograft and has a substantial therapeutic effect on
      inhibiting acute allograft rejection.

PMID- 17498388
TI  - Anesthetic effects of lidocaine hydrochloride gel using low frequency ultrasound
      of 0.5 MHz.
AB  - PURPOSE: Low-frequency ultrasound has a significant effect on the transdermal
      permeation of high molecular weight drugs. However, the rate of permeation in
      pulsed mode is quite low necessitating considerable time to apply the ultrasound.
      0.5 MHz ultrasound, which is a relatively higher frequency in the low-frequency
      range, can be applied in high intensity in continuous mode. METHODS: A transducer
      was used to administer an anesthetic drug transdermally on healthy volunteers.
      The anesthetic effect was measured following administration on placebo, lidocaine
      HCl alone and lidocaine HCl with 0.5 and 1.0 MHz ultrasound (n=8/group). RESULTS:
      In surface anesthesia, the phonophoresis group showed a significantly higher pain
      threshold than the other groups but there was no significant difference between
      the phonophoresis groups according to the ultrasound frequency. In conduction
      anesthesia, the 0.5 MHz phonophoresis group showed a significant change in their
      pain threshold and amplitude of sensory nerve action potential (SNAP) compared
      with the other groups. CONCLUSIONS: Although there are limitations in applying
      0.5 MHz ultrasound in phonophoresis for conduction anesthesia using lidocaine
      hydrochloride for a nerve block, it is more effective than the 1 Mhz that is
      widely used in clinical situations. Carbamazepine is a poor water soluble drug
      and its bioavailability is limited by dissolution rate. Dissolution, serum
      concentration and anticonvulsive effect of the drug have been evaluated after
      cogrinding with microcrystalline cellulose. A cogrinding technique was used to
      increase the dissolution, serum concentrations and anticonvulsive effect of the
      drug. A novel deconvolution technique of in vitro-in vivo correlation was
      evaluated.

PMID- 17498389
TI  - Effect of age and gender on the pharmacokinetics of R667, a novel agent for the
      treatment of emphysema, in healthy volunteers.
AB  - The purpose of the present study was to assess the impact of age and gender on
      the pharmacokinetics (PK) of R667. Thirty six healthy male and female volunteers
      (12 m 18-45 years; 12 m and 12 f > or = 65 years) received a single 1 mg oral
      dose of R667. Serial blood samples were collected for determination of plasma
      R667 and metabolite concentrations. The PK parameters of R667 were similar
      between elderly males and young males (Cmax = 9.8 vs 9.8 ng/mL; AUC(0-last) =
      50.9 vs 47.3 ng x h/mL, respectively). Exposure of R667 increased in elderly
      females compared to elderly males (Cmax = 13.1 vs 9.8 ng/mL; AUC(0-last) = 60.8
      vs 47.3 ng x h/mL, respectively). When the CL/F was corrected for BSA and V/F
      corrected for weight these differences were no longer evident. In conclusion
      these exposure differences are not considered clinically relevant, and no dose
      adjustment of R667 is required based on gender or age.

PMID- 17498390
TI  - In vitro percutaneous permeation of the repellent DEET and the sunscreen
      oxybenzone across human skin.
AB  - PURPOSE: DEET and oxybenzone are two essential active ingredients in repellent
      and sunscreen products. The percutaneous permeation of the two compounds across
      human skin from five commercially available repellent and sunscreen products was
      investigated in vitro. METHODS: Diffusion studies were carried out at 37 degrees
      C, using Franz-style diffusion cells and human epidermis (380 microm in
      thickness). The test products were evaluated either individually or in various
      combinations for up to 6 hours. Concentrations of both compounds permeated
      through the skin were measured using an HPLC assay. Permeability and permeation
      percentage of DEET and oxybenzone from different application approaches were
      calculated and statistically compared. RESULTS: The accumulated transdermal
      permeation was 0.5-25.7% for DEET and 0.3-1.6% for oxybenzone, respectively.
      Repellent lotion produced an 18-fold increase in transdermal permeation in
      comparison to that of repellent spray, while using repellent spray prior to
      sunscreen lotion resulted in the highest penetration of DEET among the study
      groups. Premixing sunscreen lotion with repellent spray at different ratios also
      produced significantly higher permeation of oxybenzone across the skin than the
      control, but other application approaches did not differentiate from the single
      sunscreen lotion. CONCLUSION: It was concluded from this study that human skin
      was less permeable to DEET and oxybenzone than artificial membranes, but was
      comparable to pig skin in permeability. DEET permeated transdermally more across
      human skin than oxybenzone, and both compounds acted as permeation enhancers when
      used simultaneously. Premixing repellent and sunscreen enhanced the overall
      penetration of both DEET and oxybenzone. Using different application sequences
      and amounts resulted in variable percutaneous permeation of DEET and oxybenzone
      through the skin.

PMID- 17498391
TI  - The metabolism of midazolam and comparison with other CYP enzyme substrates
      during intestinal absorption: in vitro studies with rat everted gut sacs.
AB  - PURPOSE: The purpose of this study was to quantify the intestinal metabolism of
      midazolam, a CYP P450 substrate, usually used as a probe for the activity of the
      isoform CYP3A4/1 and to compare it with previous results obtained for other P450
      substrates such as testosterone, dextromethorphan and bupropion, which show some
      specificities for different CYP isoforms. The aim was to shed light on the role
      of metabolism in the intestinal tissues and the relationship with efflux
      mechanisms, such as by P-glycoprotein (P-gp) and the influence of metabolism on
      bioavailability. METHODS: We used the improved everted rat gut sac model to study
      in vitro the absorption and metabolism of the different CYP isoenzyme probes:
      midazolam, testosterone, bupropion and dextromethorphan. This method enables drug
      metabolism to be studied during absorption, conditions which mimic the in vivo
      situation. The drugs and their metabolites were measured by LC-MS in the mucosal
      and serosal media and in the mucosal tissue, to give a complete picture of the
      transport and metabolism. RESULTS: Midazolam, as with the other CYP probes, was
      metabolized in everted gut sacs. The metabolites were detected in the same
      proportions in both the serosal and mucosal compartments for midazolam,
      testosterone and bupropion. In the case of dextromethorphan, the metabolite
      methoxymorphinan was found at a higher concentration in the mucosal compartment,
      indicating efflux from the cells. The transport of dextromethorphan and its
      metabolite was not modified in the presence of verapamil, a P-gp inhibitor, thus
      demonstrating that dextromethorphan and methoxymorphinan were not P-gp
      substrates. CONCLUSION: Given that the rat is a widely used species for pre
      clinical studies, the everted gut sac model provides a useful tool to assess the
      role of metabolism during drug absorption by the intestine and is also capable of
      demonstrating P-glycoprotein mediated transport.

PMID- 17498392
TI  - Dose-dependent pharmacokinetics of telithromycin after intravenous and oral
      administration to rats: contribution of intestinal first-pass effect to low
      bioavailability.
AB  - PURPOSE: To evaluate the pharmacokinetics of telithromycin after intravenous and
      oral administration and to find the reason for incomplete F value (first pass
      effect) after intravenous, intraportal, intragastric, and intraduodenal
      administration to rats. METHODS: Telithromycin was administered intravenously or
      orally at doses of 20, 50, and 100 mg/kg to rats. And hepatic, gastric, and
      intestinal first-pass effects of telithromycin were also measured after
      intravenous, intraportal, intragastric, and intraduodenal administration at a
      dose of 50 mg/kg to rats. RESULTS: The dose-normalized AUC values of
      telithromycin were dose-dependent (increased with increasing doses) after both
      intravenous and oral dose ranges studied, possibly due to saturable metabolism of
      telithromycin. After oral administration (50 mg/kg), approximately 4.06% of oral
      dose was not absorbed, F was approximately 27.5%, and the intestinal first-pass
      effect was approximately 63.4% of oral dose. The first-pass effects of
      telithromycin in the lung, heart, stomach, and liver were almost negligible, if
      any, in rats. CONCLUSIONS: The low F of telithromycin at a dose of 50 mg/kg was
      mainly due to considerable intestinal first-pass effect, approximately 63.4% of
      oral dose, in rats.

PMID- 17498394
TI  - Hyperthyroidism patients have shorter onset and duration time of rocuronium than
      euthyroidism patients.
AB  - PURPOSE: The possibility of altered response to nondepolarizing muscle relaxants
      in hyperthyroidism patients has not been documented. The present study was
      conducted to observe the onset and duration of rocuronium induced neuromuscular
      blockade in hyperthyroidism patients. METHODS: Eighteen hyperthyroidism patients
      undergoing subtotal thyroidectomy (H group) and eighteen euthyroidism patients
      undergoing operation on neck (E group) were studied. Anesthetized with propofol
      and fentanyl, all patients received rocuronium 0.6 mg/kg. The twitch high of
      adductor pollicis muscle was monitored by acceleromyography. The onset, the
      duration of the initial dose, the durations of the repeated maintenance doses,
      the repeated times, and the total doses of rocuronium were observed. RESULTS: The
      onset time of rocuronium in H group was significantly shorter than that in E
      group (P<0.05). The duration of the initial dose as well as the durations of the
      repeated maintenance doses in H group was significantly shorter than that in E
      group (P<0.05). The repeated times and the total dosage of rocuronium in H group
      were significantly more than that in E group (P<0.05). CONCLUSIONS:
      Hyperthyroidism patients experience a shorter onset time, a shorter duration, and
      require larger doses of rocuronium than euthyroidism patients.

PMID- 17498395
TI  - Enhanced nuclear delivery and cytotoxic activity of hydroxycamptothecin using o/w
      emulsions.
AB  - PURPOSE: Hydroxycamptothecin-Emulsions (HCPT-E), being a promising delivery
      system for intravenous applications, were prepared. Here we evaluated the
      relation of cytotoxicity and intracellular drug amounts. The mechanism of the
      enhanced antiproliferative activity was also investigated. METHODS: In vitro
      cytotoxic potential were assessed by the methyl thiazol tetrazolium (MTT) assay.
      The capability of emulsions to preserve lactone form of HCPT and the time course
      of subcellular (cytoplasm and nuclei) drug distribution in vitro of HCPT-E were
      quantified by a reversed-phase HPLC assay. RESULTS: MTT results showed that the
      antiproliferative activity of HCPT-E was stronger than that of HCPT-Injections
      (HCPT-I) which is presently used in clinic. IC50 values of HCPT-E was much lower,
      by 4 and 7 times than those of HCPT-I. HeLa cells treated with HCPT-E for 4 h
      exhibited a considerable morphology change and displayed a hint of apoptotic cell
      death at 72 h. The lactone is the key position in HCTP molecule which is
      sensitive to pH. Lactone ring of HCPT in HCPT-E was stable for longer time than
      that of HCPT-I in the presence of human plasma or culture medium. Both the
      nuclear and cytoplasmic level of HCPT in HeLa cells exposed to HCPT-E at each
      time were higher by 18 to 33 times than those treated with HCPT-I. Drug amounts
      of nuclei was higher than that of cytoplasm in HeLa cells incubated with HCPT-E
      while it was reverse in HeLa cells exposed to HCPT-I. CONCLUSIONS: HCPT-E
      improved stability of HCPT, enhanced uptake, changed its intracellular
      distribution in favor of accumulating in the intracellular targets.

PMID- 17498396
TI  - Difference between pharmacokinetics of mycophenolic acid (MPA) in rats and that
      in humans is caused by different affinities of MRP2 to a glucuronized form.
AB  - PURPOSE: Mycophenolic acid (MPA), an immunosuppressant, is excreted as its
      glucuronized form, MPAG. In humans, MPAG is mostly excreted into urine, whereas
      more than 80% of the dose is excreted into bile in rats. The aim of this study
      was to clarify the cause of the species difference. We investigated whether MPAG
      is a substrate of human organic anion transporters (hOATs), and we compared the
      affinities of multi-drug resistance-associated protein 2 (MRP2) for MPAG in rats
      and humans. METHODS: The inhibitory effects of MPAG on the uptake of typical
      substrates via hOAT1 and hOAT3 were determined using HeLa cells heterologously
      expressing hOAT1 and Xenopus laevis oocytes heterologously expressing hOAT3. MPAG
      transport activity via hOAT1 and hOAT3 was determined by the two-microelectrode
      voltage-clamp technique using Xenopus laevis oocytes expressing hOAT1 and hOAT3.
      The affinities of MPAG for hMRP2 and rMrp2 were determined by the inhibitory
      effects of MPAG on p-aminohippuric acid (a typical substrate) uptake using
      membrane vesicles expressing hMRP2 or rMrp2. RESULTS: MPAG inhibited the uptake
      of PAH via hOAT1 and hOAT3, and calculated IC50 values were 222.6+/-26.6 microM
      and 41.5+/-11.5 microM, respectively. However, MPAG was not transported by hOAT1
      and hOAT3. MPAG strongly inhibited the uptake of PAH via both rMrp2 and hMRP2.
      However, the magnitudes of inhibitory effects were different. The calculated IC50
      values were 286.2+/-157.3 microM and 1036.8+/-330.5 microM, respectively.
      CONCLUSION: MPAG is not a substrate but is an inhibitor of hOAT1 and hOAT3. The
      affinity of rMRP2 to MPAG was about 3.6 times as high as that of hMRP2.
      Therefore, the difference of affinity between hMRP2 and rMrp2 is a possible
      mechanism of the difference of excretion ratio of MPAG between rats and human.

PMID- 17498411
TI  - Patch testing for evaluating drug reactions due to systemic antibiotics.
AB  - Several studies have evaluated patch testing for the diagnosis of drug eruptions,
      but widespread acceptance of this procedure is lacking in North America. The
      objective of this review is to address patch testing for the evaluation of
      exanthematous drug eruptions due to systemic antibiotics, using a MEDLINE
      database search for articles in English on patch testing for systemic drug
      eruptions caused by antibiotics.

PMID- 17498397
TI  - Perspectives of biodegradable natural polysaccharides for site-specific drug
      delivery to the colon.
AB  - The ability to deliver drugs to the human colon in a specific manner has become
      feasible over the years. Targeting pharmaceutical drugs to the colon makes it
      possible to achieve local or systemic drug delivery to this site. To deliver the
      compounds in a non-degraded form to the lower part of the gastrointestinal tract,
      they must first of all pass through the stomach, the upper part of the intestine
      and must use the characteristics of the colon to specifically release the drugs
      in this part of the digestive tract. Among the different approaches available to
      achieve targeted drug release to the colon, the use of especially biodegradable
      polymers holds great promise. This family of natural polymers has great appeal to
      drug delivery as it is comprised of polymers with a large number of derivatizable
      groups, a wide range of molecular weights, varying chemical compositions, and,
      for the most part, low toxicity and biodegradability yet high stability. The most
      favorable property of these materials is their approval as pharmaceutical
      excipients. Polysaccharidases are bacterial enzymes that are available in
      sufficient quantity to be exploited in colon targeting. Bacterial sources of
      polysaccharidases as well as a detailed treatise of the enzymatic flora of the
      colonic region is reviewed, followed by a wide range of the polysaccharides which
      can be used solely for the purpose of colon-specific drug delivery. Present
      article also discusses few of the mechanisms by which members of the intestinal
      microbiota degrade complex polysaccharides. A final overview of the various
      approaches to target drugs to the colon utilizing natural polysaccharides, the
      limits and the future developments in this field with these natural polymers is
      discussed which leads to the conclusion that polysaccharides show high potential
      in achieving colon-specific drug delivery.

PMID- 17498412
TI  - Common contact allergens associated with eyelid dermatitis: data from the North
      American Contact Dermatitis Group 2003-2004 study period.
AB  - BACKGROUND: Allergic contact dermatitis can be manifest as an eruption confined
      to the eyelids. In regard to this specific presentation, only limited information
      on which to base the selection of patch tests for proper evaluation is available.
      OBJECTIVE: To identify the contact allergens most frequently found to be both
      patch test positive and relevant when only the eyelids are involved. METHODS:
      Data collected from 2003 to 2004 by the North American Contact Dermatitis Group
      (NACDG) were analyzed for relevant allergens in the setting of dermatitis on the
      eyelids only. Data on eyelid dermatitis patients whose relevant allergens were
      not among the 65 allergens used for screening during this study period were also
      tabulated. RESULTS: Data showed that 268 patients had only eyelid dermatitis and
      a final diagnosis of allergic contact dermatitis. In 193 (72%) of these,
      reactions were of current relevance and were identified from a screening series
      of 65 allergens. The top 26 allergens identified 65% of cases (175 cases). Gold
      was the most frequently encountered allergen (22 of 175 cases [12.5%]). Of the
      268 cases, 33 showed relevant reactions to an allergen that was not among the 65
      NACDG standard screening allergens. No specific allergen was identified in the
      remaining 42 cases. CONCLUSION: The top 26 allergens identified in this study
      represent a potential eyelid dermatitis screening series.

PMID- 17498413
TI  - A population-based survey of eczema prevalence in the United States.
AB  - BACKGROUND: Eczema and atopic dermatitis (AD) are recognized as major health
      problems worldwide. Prevalence estimates are as high as one-third of the
      population, depending on the country studied, the age range of the subjects, and
      the diagnostic criteria used. National estimates of prevalence for the US
      population are lacking. OBJECTIVE: To examine the public health problem posed by
      eczema, AD, and eczematous conditions in the United States by analyzing disease
      and symptom prevalence, estimating the number of undiagnosed cases, and assessing
      comorbidities. METHODS: A self-administered questionnaire was sent to a sample of
      households (N = 60,000) representative of the US population. A designated member
      responded with information on symptoms, diagnoses, and impact for affected
      household members; 42,249 households (70%) responded, representing 116,202
      individuals. Empirical eczema was defined by itching/scratching and red/inflamed
      rash or excessive dryness/scaling. Empirical AD was defined by itching/scratching
      and red/inflamed rash, excessive dryness/scaling, skinfold location, early onset,
      symptoms lasting or 14 days, or a physician diagnosis of asthma or of allergic
      rhinitis or hay fever. RESULTS: Of the population studied, 17.1% reported at
      least one of four eczematous symptoms; empirically defined eczema was found in
      10.7%, and empirically defined AD was found in 6%. Prevalence decreased with
      increasing income. Approximately two-thirds of individuals with an empirical
      diagnosis of eczema or AD had moderate to severe symptoms, one-third had sleep
      disturbances, and one-quarter had chronic unremitting symptoms. Just over one
      third (37.1%) of those with symptoms reported a physician diagnosis. Peak onset
      for empirical AD occurred in the group of subjects aged <or= 5 years. For
      empirical eczema, peak onset occurred in the group aged 18 to 29 years, and
      comorbid asthma and hay fever/allergic rhinitis were more prevalent. CONCLUSIONS:
      A substantial proportion of the US population has symptoms of eczema or
      eczematous conditions; 31.6 million met the empirical symptom criteria for
      eczema, and 17.8 million met the empirical criteria for AD. Most cases are not
      diagnosed by a physician, which indicates that these conditions are undertreated
      and/or managed with nonprescription remedies.

PMID- 17498414
TI  - Patch-test reactions to formaldehydes, bioban, and other formaldehyde releasers.
AB  - BACKGROUND: Contact allergy to formaldehyde, Bioban, and other formaldehyde
      releasers and cross-reactivity between them have been reported in the literature;
      however, not many studies have data on this cross-reactivity. OBJECTIVE: To study
      (1) the rates of allergy to formaldehyde and to Bioban and other formaldehyde
      releasers and (2) the rates of cross-reactivity between them. METHODS: We present
      a retrospective chart analysis of patch-test results for all patients referred
      for allergic contact dermatitis testing at the Milton S. Hershey Medical Center
      from June 2004 to September 2005. Anyone allergic to formaldehyde, Bioban, or
      other formaldehyde releasers was included. Cross-reactivity between the agents
      was then analyzed. RESULTS: The charts of 210 patients were analyzed. Of these
      patients, 24 (11%) were allergic to formaldehyde, Bioban, or other formaldehyde
      releasing agents. Seventeen (8.1%) of the patients were allergic to formaldehyde,
      15 (7.1%) were allergic to Bioban, and 20 (9.5%) were allergic to other
      formaldehyde-releasing agents. Eleven (65%) of the 17 formaldehyde-allergic
      patients were also allergic to Bioban. Of the 20 patients allergic to
      formaldehyde-releasing agents, 14 (70%) were also allergic to one of the three
      Bioban products tested. Of the 15 patients allergic to Bioban, 11 (73%) were
      allergic to formaldehyde, 14 (93%) were allergic to formaldehyde-releasing
      agents, and 11 (73%) were allergic to both formaldehyde and formaldehyde
      releasing agents. CONCLUSION: A high cross-reactivity rate between formaldehyde,
      Bioban, and other formaldehyde-releasing agents was found.

PMID- 17498415
TI  - Allergic contact dermatitis caused by colophony in an epilating product.
AB  - Considering the widespread use of colophony-containing epilating products and the
      frequency of sensitization to colophony, it is somewhat surprising that reports
      of allergic contact dermatitis from these products are so infrequent. Reactions
      to colophony can be severe, and they may present even after initial exposure
      (primary sensitization). Consequently, health care practitioners should be aware
      of potential colophony-induced allergic contact dermatitis in patients exposed to
      epilating products. Patch testing with commercially available colophony
      unmodified rosins often fails to detect reactions to the modified-rosin
      derivatives found in the actual epilating products. Therefore, the evaluation of
      colophony allergy may require testing with the patient's own products as well as
      additional modified colophony rosins. We describe a case of allergic contact
      dermatitis caused by colophony found in an epilating product.

PMID- 17498416
TI  - Contact allergy to pentylene glycol.

PMID- 17498417
TI  - Improving post-patch-test education with the contact allergen replacement
      database.

PMID- 17498419
TI  - Chloroxylenol.

PMID- 17498420
TI  - Topical minocycline and tetracycline rinses in treatment of recurrent aphthous
      stomatitis: a randomized cross-over study.
AB  - Recurrent aphthous stomatitis (RAS) is a common ulcerative condition of the oral
      mucosa. We assessed minocycline and tetracycline oral rinses in patients with
      frequent episodes of RAS in a clinical randomized crossover trial. Seventeen
      patients with high frequency recurrent minor RAS were randomly allocated to a
      cross-over topical therapy with 0.2 percent minocycline or 0.25 percent
      tetracycline aqueous solution mouthwash. The minimum interval between the cross
      over was 30 days. The intensity of pain was recorded daily using a visual
      analogue scale. Minocycline mouthwashes as compared to topical tetracycline
      rinses resulted in significantly improved pain control, by reducing the severity
      and duration of pain. Topical minocycline rinse may be a potential treatment for
      other mucosal diseases that result in mucosal ulceration and pain.

PMID- 17498421
TI  - Why do so many clinicians believe that recurrent zoster is common?

PMID- 17498422
TI  - Transcending the language barrier--creation of a multilingual dermatology
      website.
AB  - In a linguistically diverse society, healthcare professionals must overcome the
      daunting task of effectively communicating with patients who speak a different
      language. In effort to aid healthcare professionals and their patients, an on
      line dermatology patient education resource was created with links to various
      skin related topics in over 30 languages. The development of the on-line
      resource, key features of the information available on the website, and
      limitations experienced during its creation are discussed in the article.

PMID- 17498423
TI  - Unraveling the paradoxes of HIV-associated psoriasis: a review of T-cell subsets
      and cytokine profiles.
AB  - HIV-associated psoriasis appears paradoxical, being a T-cell mediated disease in
      the face of decreasing T-cell counts. Furthermore, psoriasis is generally
      mediated by type-1 cytokines, whereas in HIV, type-2 cytokines tend to
      predominate. How can one have psoriasis in the essentially Th2 environment of
      HIV? The details and pertinent research regarding T cell subsets and cytokine
      profiles in psoriasis, HIV, and HIV-associated psoriasis were reviewed. It
      appears that both in the presence and absence of HIV infection, psoriasis is
      largely mediated by memory CD8 T cells, and that IFN-gamma secreted by these
      cells and others is of key importance. Studying psoriasis in a model such as HIV
      in which certain elements of the immune system are stripped away or altered may
      help us better understand the pathogenic mechanisms and potential treatment
      targets for psoriasis vulgaris.

PMID- 17498424
TI  - Generalized purpuric lichen nitidus. Report of a case and review of the
      literature.
AB  - Generalized purpuric lichen nitidus is an extremely rare form of lichen nitidus.
      We present the third documented case of this uncommon dermatosis, which was
      treated successfully with orally administered cyclosporine. During a 12-month
      follow-up after the cessation of the drug, no recurrence was noticed.

PMID- 17498425
TI  - Exuberant molluscum contagiosum as a manifestation of the immune reconstitution
      inflammatory syndrome.
AB  - Immune reconstitution inflammatory syndrome (IRIS) is a recently described entity
      in which severely immunodepressed HIV patients, after being started on HAART,
      develop inflammatory reactions to several pathogens. We present a patient who
      developed extensive Molluscum Contagiosum (MC) lesions shortly after being
      started on HAART. With the progression of immunoreconstitution, the lesions
      healed spontaneously. Molluscum contagiosum lesions are presumably common in IRIS
      but underreported. We point out this case for its striking clinical picture and
      well-documented relation to immunoreconstitution to draw attention to this IRIS
      manifestation.

PMID- 17498426
TI  - Massive nodular melanoma: a case report.
AB  - Melanoma is the sixth most common cancer in the United States, and its incidence
      rates are currently increasing faster than for any other cancer. Nodular melanoma
      often carries a poor prognosis because of local invasion and early distant
      metastasis. Herein, we report a case of the largest primary melanoma in the
      current literature, along with the management strategy of a primary tumor of this
      magnitude.

PMID- 17498427
TI  - A review and report of blistering distal dactylitis due to Staphylococcus aureus
      in two HIV-positive men.
AB  - Blistering distal dactylitis (BDD) is attributed to infection with group A beta
      hemolytic Streptococcus or Staphylococcus aureus (SA). Although initially
      described in children, BDD subsequently has also been reported in adults. It
      occurs in the immunocompetent and immunocompromised individuals. This report
      notes two HIV-positive men with BDD, one with bullae and the other with erosions
      caused by SA, effectively treated with amoxicillin trihydrate/clavulanate
      potassium. This report highlights the reasoning behind adjusting empiric therapy
      to account for SA, that BDD can present with erosions, and that the course and
      presentation of BDD in HIV-positive patients mirrors that of non HIV-positive
      patients.

PMID- 17498428
TI  - Diffuse cutaneous melanosis in malignant melanoma.

PMID- 17498429
TI  - Imiquimod-induced vitiligo.

PMID- 17498430
TI  - Diagnosis of loxoscelism in two Turkish patients confirmed with an enzyme-linked
      immunosorbent assay (ELISA) and non-invasive tissue sampling.
AB  - Confirmed envenomations due to Loxosceles reclusa have not been previously
      documented in Turkey, to our knowledge. This brief report describes two Turkish
      patients with suspected envenomation by Loxosceles spider bites on the eyelids.
      Material obtained by swabbing the lesions with gauze was tested using a venom
      specific enzyme-linked immunosorbent assay (ELISA). Both patients tested positive
      for the presence of Loxosceles venom.

PMID- 17498431
TI  - Schwannoma of the eyelid: report of two cases.
AB  - Schwannomas are rare benign neurogenic tumors that show differentiation of
      Schwann cells that form the neural sheath. Only five reports of eyelid
      schwannomas in adults have been found in the English literature. We report the
      unusual cases of two females, aged 41 and 70 years, who developed eyelid
      schwannomas. Neither tumor was diagnosed clinically; both were erroneously
      considered as epidermal inclusion cysts. The masses were surgically removed by
      excisional biopsy. The histopathological examination showed encapsulated tumors
      composed of interlacing bundles of spindle cells with slightly wavy nuclei.
      Immunocytochemistry for S-100 protein was strongly positive. The diagnosis of
      schwannoma was made. After 12 and 2 years of follow-up, no recurrences have been
      observed. This entity should be included in the differential diagnosis of eyelid
      tumors.

PMID- 17498432
TI  - Multiple furunculoid myiasis on the scalp of a child.
AB  - Cutaneous myiasis is easy to diagnose and treat if clinicians are aware of the
      condition. Because of widespread travel, physicians may encounter this
      infestation in patients living in geographical regions where the condition is
      rare. A child is presented with cutaneous myiasis that presented as furuncle-like
      nodules on the scalp. The larvae were identified as a stage of the bluebottle
      like fly, Dermatobia hominis.

PMID- 17498433
TI  - Benign nerve sheath myxoma (myxoid neurothekeoma) in the leg.
AB  - Myxoid neurothekeoma is a rare benign cutaneous neoplasm of nerve sheath origin
      and is also called as benign nerve sheath myxoma. This entity is seen in head,
      neck and upper extremity and seldom on the lower limb. A myxoid neurothekeoma in
      the lower leg of a 33-year-old woman is described.

PMID- 17498434
TI  - Recurrent cutaneous leishmaniasis presenting as sporotrichoid abscesses: a rare
      presentation near Afghanistan border.
AB  - Cutaneous leishmaniasis caused by Leishmania tropica and Leishmania major is
      endemic in Pakistan and is the second most prevalent vector-borne disease in the
      country (after malaria). We report a case of non-ulcerating, sporotrichoid
      cutaneous leishmaniasis that recurred 2 years after successful treatment of two
      typical leishmaniasis ulcers. The patient came from Kohat, a border town in the
      northwestern region of Pakistan about 50 miles east of Afghanistan. It is
      important for physicians to be familiar with unusual presentations of this common
      condition.

PMID- 17498435
TI  - Successful combined pentoxifylline and intralesional triamcinolone acetonide
      treatment of severe pretibial myxedema.

PMID- 17498436
TI  - Griscelli syndrome: a new phenotype with circumscribed pigment loss?
AB  - Griscelli syndrome is a rare genetic immunodeficiency disorder characterized by
      pigment dilution, recurrent cutaneous and pulmonary infections, neurological
      deterioration, hypogammaglobulinemia, and defective cell-mediated immunity.
      Mutations of three distinct genes have been described in Griscelli syndrome with
      different phenotypes. The disease is usually fatal by the first decade of life.
      We report a 20-year-old female with Griscelli syndrome with circumscribed pigment
      loss over thighs and abdomen in addition to diffuse pigment dilution. An
      accelerated phase, similar to that described in Chediak-Higashi syndrome, was
      also observed in our case in the form of neurological deterioration. Survival of
      the patient beyond the first decade of life in the absence of specific therapy
      was also a distinctive feature.

PMID- 17498437
TI  - Melanoma of the nipple mimicking Paget's disease.

PMID- 17498438
TI  - Angiokeratoma of the glans penis: clinical, histopathological and dermoscopic
      correlation.
AB  - Angiokeratoma is a benign vascular lesion characterized by vascular ectasia in
      the upper dermis and hyperkeratosis. We report a case with lesions on the glans
      penis, a very rare location. In addition, we report the dermoscopic findings.

PMID- 17498439
TI  - Chronic, progressive enlargement of the lower lip in a healthy girl.

PMID- 17498440
TI  - Acrochordon-like basal cell carcinomas in patients with basal cell nevus
      syndrome.
AB  - Basal cell nevus syndrome is an autosomal dominant disorder characterized by
      multiple basal cell carcinomas, along with numerous other documented clinical
      features. Acrochordons (or skin tags) are common benign neoplasms that are
      appropriately left untreated in most patients. We describe two patients with
      known BCNS who were found to have multiple BCCs that clinically resembled
      acrochordons. Our findings support the biopsy of acrochordon-like growths in
      patients with basal cell nevus syndrome to rule out basal cell carcinoma.

PMID- 17498441
TI  - Pimecrolimus 1 percent cream and pulsed dye laser in treatment of a patient with
      reticular erythematous mucinosis syndrome.
AB  - We report on the efficacy of twice daily application of pimecrolimus 1 percent
      cream in a 48-year-old woman with reticular erythematous mucinosis (REM) syndrome
      and compare its results with pulsed dye laser (PDL) on the other side of her
      chest and back. The patient was previously treated by hydroxychloroquine but only
      a fair response was observed. After application of 5 months of pimecrolimus, the
      lesions completely resolved and the result was comparable with the other side of
      her body treated by pulsed dye laser PDL. Topical pimecrolimus and pulsed dye
      laser appear to be effective and safe treatments for REM.

PMID- 17498442
TI  - Painful ulcer on the breast.

PMID- 17498443
TI  - Papulo-vesicular eruption.

PMID- 17498444
TI  - Another injection-free method to effect analgesia when injecting botulinum toxin
      for palmar hyperhidrosis: cryoanalgesia.

PMID- 17498445
TI  - Koebner's phenomenon in Henoch Schoenlein purpura and role of pressure in its
      causation.

PMID- 17498446
TI  - Squamous cell carcinoma arising on a skin graft 64 years after primary injury.
AB  - Malignant degeneration of a chronic wound is often described by the term,
      Marjolin's ulcer. We present a case of a squamous cell carcinoma that developed
      in a patient 64 years after the initial injury during World War II. Tissue
      contusion and detachment required repeated surgery and full skin grafting in
      several hospitals. The patient had a persistent ulcer in the right popliteal
      region for the last 3 years. Excisional biopsy in our department showed a bifocal
      low-grade invasive squamous cell carcinoma of the skin. Because of extensive
      inflammation and previous scar formation it was difficult to determine the status
      of the surgical margins. Therefore, we proceeded with amputation at the right
      thigh. Some 6 months after surgery the general condition of the patient remains
      excellent.

PMID- 17498447
TI  - Erythema Palmare hereditarium (red palms): Lane's disease.

PMID- 17498448
TI  - Cutaneous Lichenoid dermatitis associated with imatinib mesylate.

PMID- 17498449
TI  - Increase of intracellular methylglyoxal levels as a mode of action of retinoids
      against psoriasis.

PMID- 17498450
TI  - [Surgical treatment of gastroesophageal reflux disease with atypical
      manifestations: the wheel of fortune or Russian roulette?].

PMID- 17498451
TI  - [Mechanical bowel preparation. A necessity or nothing more (or less) than the
      weight of tradition?].
AB  - Mechanical bowel preparation is a traditional procedure for preparing patients
      for colorectal surgery. This practice aims to reduce the risk of postoperative
      infectious complications since colonic fecal content has classically been related
      to stool spillage during surgery and anastomotic disruption. However, increasing
      evidence against its routine use can be found in experimental studies, clinical
      observations, prospective studies, and meta-analyses. We performed a review of
      the literature on mechanical bowel preparation and its consequences. There is no
      clear evidence that preoperative bowel cleansing reduces the septic complications
      of surgery and routine use of this procedure may increase anastomotic leaks and
      morbidity. Therefore, the results suggest that mechanical preparation is not
      required in elective colon and rectal surgery and that its use should be
      restricted to specific indications such as small nonpalpable tumors to aid their
      localization during laparoscopic procedures or to enable intraoperative
      colonoscopy. The role of mechanical bowel preparation in rectal surgery is not
      well defined and further trials with a larger number of patients are required.

PMID- 17498452
TI  - [Prevention of sepsis in asplenic patients].
AB  - Although the high mortality rate from infectious causes in asplenic patients has
      been well known since the beginning of the twentieth century, rates of antibiotic
      prophylaxis in these patients continue to be worryingly low. Consequently, we
      reviewed the causes of these high mortality rates with a view to recommending
      preventive measures. The attitude to prophylaxis in these patients depends on age
      and the cause of splenectomy both in vaccination and antibiotic prophylaxis. The
      immune status of these patients is decisive in antibiotic prophylaxis, as this
      treatment will differ in patients splenectomized after a traffic accident and in
      those splenectomized for lymphoma.

PMID- 17498453
TI  - [Results of laparoscopic fundoplication in gastroesophageal reflux disease with
      atypical manifestations].
AB  - INTRODUCTION: Gastroesophageal reflux disease (GERD) may present with typical
      (heartburn and regurgitation) and atypical symptoms (cough, asthma, non-cardiac
      chest pain). Laparoscopic fundoplication has been performed for approximately 10
      years, with results similar to or better than those obtained with open antireflux
      procedures. The aim of this study was to evaluate the clinical and functional
      results of laparoscopic fundoplication in patients with GERD and atypical
      symptoms. PATIENTS AND METHOD: There were 158 consecutive patients with GERD who
      underwent a 360 degrees laparoscopic fundoplication (January 1999 to March 2006)
      and 27 patients had atypical symptoms. All patients underwent preoperative
      manometry and 24 hour pH-metry and 78% underwent the same tests postoperatively
      (at 6 months). Data from hospital records were analyzed and a clinical telephone
      survey was conducted. RESULTS: There was no mortality and no conversions were
      required. The median length of follow-up was 21 months. All atypical symptoms
      (cough, chest pain, asthma, dysphonia and hoarseness) were significantly reduced
      (p < 0.05). There was no relationship between symptom persistence in five
      patients and pathologic acid reflux, except in one patient. Eighty-nine percent
      of the patients responded to the telephone survey; of these, 79% had no symptoms.
      The median satisfaction score was 9 (from 0 to 10). CONCLUSIONS: Laparoscopic
      fundoplication for GERD with atypical symptoms is a safe procedure with good
      results (clinical and functional) in trained groups patients. Moreover a high
      satisfaction rate is obtained.

PMID- 17498454
TI  - [Definition of processes and indicators for the management of vascular accesses
      for hemodialysis].
AB  - INTRODUCTION: The prevalence of renal replacement therapy has increased,
      affecting 885 patients per million inhabitants. More than 50% of these patients
      require hemodialysis with permanent vascular access. In our center a
      multidisciplinary group was organized to manage processes related to vascular
      access for hemodialysis. OBJECTIVES: To define processes for the management of
      vascular access for hemodialysis and to evaluate these processes. MATERIAL AND
      METHOD: Setting. Level III hospital in the autonomous community of Madrid serving
      485,000 inhabitants. STUDY PERIOD: 2002-2004. METHODOLOGY: A multidisciplinary
      working group was set up. The three most frequent processes were defined and
      described. Flow charts were used for graphical representation. Quality criteria
      and indicators were defined with prospective monitoring of electronic medical
      records, design of a specific surgical protocol, and retrospective analysis.
      RESULTS: Comparison of the results with the literature. First vascular access.
      The percentage of patients with arteriovenous fistulas on starting hemodialysis.
      Percentage of prevalent patients with venous access (autologous fistula,
      prosthetic device, catheter). Maintenance of access: Rate of thrombosis in
      autologous-prosthetic arteriovenous fistulas. Percentage of rescued arteriovenous
      fistulas after thrombosis. Rate of temporary catheters. Resource management.
      Percentage of ambulatory interventions. Rate of admissions related to
      arteriovenous fistulas. CONCLUSIONS: Arteriovenous fistulas are the main source
      of morbidity and hospital admission in patients with chronic renal failure in
      hemodialysis programs. Multidisciplinary management achieves results above the
      standards described in the literature. There do not appear to be other
      determining factors for these results, since the technical procedures performed
      do not differ from those described in the literature.

PMID- 17498455
TI  - [Technical features of interest in lymphatic basin localization in breast cancer
      sentinel lymph node biopsy].
AB  - OBJECTIVES: The sentinel node is defined as the node with the highest probability
      of being involved in the case of lymphatic spread from a tumor. Accurate
      identification and biopsy of this node can avoid unnecessary lymphadenectomies.
      The aim of this study was to determine if there are differences in the number of
      isolated sentinel lymph nodes in breast cancer according to whether a mixed
      technique (vital dye plus isotopic tracer) or radiotracer alone is used and if
      there are differences in the detection of more than one lymphatic basin and in
      the number of lymphatic nodes depending on the site of tracer injection. PATIENTS
      AND METHOD: A total of 173 sentinel lymph node biopsies in 173 women with breast
      cancer were studied taking into account the technique (mixed [n = 109] or
      radiotracer alone [n = 64]) and the location of tracer injection (periareolar [n
      = 81], intra and/or peritumoral [n = 92]). The number of lymphatic basins and the
      number of sentinel nodes were compared among the distinct groups resulting from
      the combination of the 2 parameters. RESULTS: Simultaneous drainage to both the
      axilla and internal mammary chain was more frequent with the intra-periareolar
      technique. The number of identified nodes was significantly higher when mixed
      techniques were compared, and was higher with periareolar injection than with the
      intra-peritumoral route. CONCLUSIONS: In breast cancer sentinel lymph node
      biopsy, the number of identified nodes is not influenced by the use of a mixed
      technique or radiotracer alone. However, the number of identified nodes is higher
      with the periareolar route than with the intra-peritumoral route. Intra
      peritumoral injection of the tracer shows a higher frequency of internal mammary
      chain drainage than periareolar injection, although this difference was not
      statistically significant.

PMID- 17498456
TI  - [Reflections on 250 interventions for colorectal carcinoma metastases to the
      liver].
AB  - INTRODUCTION: The best results in the treatment of colorectal cancer metastases
      to the liver are currently achieved with surgical resection performed under high
      quality standards. OBJECTIVES. To analyze the results and quality standards of
      the surgical treatment of colorectal cancer liver metastases in a referral liver
      unit over an 11-year period. PATIENTS AND METHOD: From January 1995 to December
      2005, 250 surgical interventions were performed in 221 patients diagnosed with
      colorectal cancer liver metastases, resulting in 201 hepatic resections. RESULTS:
      Nineteen percent of patients were >/= 70 years old and comorbidity was present in
      54%. Of the 201 hepatic resections, 8.5% were second resections. Major
      hepatectomy was performed in 39% of the patients. R0 resection was achieved in
      85% of the patients. Blood transfusions were not required in 80% of the patients.
      The median length of postoperative stay was 6 days. Postoperative mortality was
      nil and morbidity was 19%. Morbidity was associated with the number of resected
      segments and the need for blood transfusion. The estimated 1-, 3- and 5-year
      cumulative survival rates were 96%, 69% and 52%, respectively, while estimated
      disease-free survival rates were 58%, 32% and 24%, respectively. CONCLUSIONS:
      Resection of colorectal cancer liver metastases is an effective therapeutic
      alternative if high current quality standards are achieved.

PMID- 17498457
TI  - [Laparoscopic biopsy of non-digestive intra-abdominal masses].
AB  - INTRODUCTION: Laparoscopic surgery offers an alternative diagnostic technique in
      multiple diseases requiring biopsy of non-digestive intra-abdominal masses in
      which image-guided biopsy cannot be performed. Laparoscopic biopsy aims to reduce
      the surgical aggression and complications associated with laparotomy and favors
      the early treatment of malignancies. PATIENTS AND METHOD: We performed a
      retrospective descriptive study of our results in a series of patients in our
      hospital with intra-abdominal masses of unknown etiology who underwent
      laparoscopic surgery between January 2001 and April 2006. None of the patients
      were candidates for image-guided percutaneous biopsy. RESULTS: We carried out 23
      biopsies: 8 retroperitoneal (34.7%), 5 mesenteric (21.7%), 5 hepatic, 4 pelvic,
      and 1 in the iliac chain, as well as 5 complementary biopsies. In all patients,
      sufficient material for histologic diagnosis was obtained. The mean operating
      time was 71 minutes. Length of hospital stay was less than 24 hours in 61% of the
      patients. The median length of hospital stay was 1.5 days. CONCLUSIONS: The
      laparoscopic approach allows complete visualization and examination of the entire
      peritoneal cavity. Laparoscopic biopsy is a safe and effective procedure with
      excellent patient recovery and allows early definitive treatment.

PMID- 17498458
TI  - [Gangrenous pyoderma and enterocutaneous fistulas after ileal pouch-anal
      anastomosis].
AB  - We describe the medical-surgical management of a patient with a complex
      inflammatory bowel disease who developed 2 acute episodes of pyoderma gangrenosum
      and enterocutaneous fistulas after ileal pouch-anal anastomosis for ulcerative
      colitis. The rarity of this postsurgical complication is emphasized. A good
      response to topical tacrolimus was achieved in cutaneous wounds. A less favorable
      response to infliximab was achieved in the abdominal fistulas, requiring surgical
      excision of the pouch.

PMID- 17498459
TI  - [Xiphoid metastasis from duodenal cancer].
AB  - Duodenal cancer has a low prevalence in the general population. Metastases from
      this neoplasm usually affect the lymph nodes, liver or lung. Bone metastases from
      duodenal cancer are highly infrequent and xiphoid localization is exceptional. We
      present the case of a patient who, 5 years after undergoing surgery for duodenal
      adenocarcinoma, developed xiphoid metastasis. We discuss the utility of positron
      emission tomography in the diagnosis of this entity and the therapeutic options.

PMID- 17498460
TI  - [Two exceptional cases of pancreatic tumor].
AB  - Pancreatic cancer carries a poor prognosis. The only potentially curative
      treatment is surgical resection. However, this procedure can only be performed in
      a few cases due to presentation of the tumor in advanced stages. We present 2
      exceptional cases of pancreatic cancer presentation. Case 1: A 59-year-old man
      presented with recurrent melena despite endoscopic sclerosis of a duodenal ulcer.
      A computed tomography (CT) scan revealed a 7-cm mass in the head of the pancreas
      infiltrating the second portion of the duodenum. Duodenal biopsy showed a poorly
      differentiated carcinoma. Palliative pancreatoduodenectomy was performed. Case 2:
      A 49-year-old man presented with sporadic pain in the right hypochondrium and a
      familial history of pancreatic cancer in first and second degree relatives. CT
      and magnetic resonance imaging revealed a 1-cm cystic lesion in the head of the
      pancreas. Cytology showed mucoid material and atypia. Given a probable diagnosis
      of mucinous cystoadenoma, pancreatoduodenectomy was performed.

PMID- 17498461
TI  - [Pelvic metastases from follicular thyroid cancer].

PMID- 17498462
TI  - [Extragenital endometriosis as a cause of acute inguinal pain in a woman of
      reproductive age].

PMID- 17498463
TI  - [Transgastric percutaneous drainage of pancreatic pseudocyst].

PMID- 17498464
TI  - [Hemoperitoneum due to solitary sigmoid diverticulum].

PMID- 17498465
TI  - [Retroperitoneal myxoid liposarcoma with bone metaplasia].

PMID- 17498466
TI  - [Vestibular evoked myogenic potentials and benign paroxysmal positional vertigo].
AB  - OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) seems to occur because of
      otoconia migration into the semicircular canals or their adherence to the cupula.
      Although the origin of these otoconia lies in the macula of the utricle,
      vestibular evoked myogenic potentials (VEMPs) can be used assess saccular
      function. The aim of this study is to assess the saccular function in patients
      diagnosed with BPPV. PATIENTS AND METHOD: Nineteen patients diagnosed with BPPV
      of the posterior semicircular canal were included in this study. Their auditory
      function and their caloric, rotatory chair, and VEMP responses were tested.
      Ipsilateral and contralateral VEMP thresholds, ipsilateral and contralateral p13
      and n23 latencies at 100 dB, inter-peak amplitude and the interaural amplitude
      difference were determined. RESULTS: We found a lack of VEMP response in 52 % of
      the ears with BPPV. When adjusted for bilateral absence, VEMP response was absent
      in 20.3 % of ears. CONCLUSIONS: Some patients with idiopathic BPPV show a degree
      of saccular dysfunction.

PMID- 17498467
TI  - [Morphometric study of the mastoid segment of the facial nerve].
AB  - OBJECTIVE: Our study emphasizes the relationship between the temporal bone
      structures and the mastoid portion of the facial nerve. MATERIAL AND METHODS:
      Thirty-two temporal bones taken from adult cadavers of both sexes subjected to
      tympanoplastic procedure were used to make reference measures of the mastoid
      portion of the facial nerve. Appropriate instruments were used for measurement
      and statistic analysis was subsequently performed. RESULTS: The digastric ridge
      presented a positive correlation with the stylomastoid foramen in comparison with
      the sigmoid sinus (P=.03). There was a correlation between the position of the
      short apophysis of the incus and the position of the facial nerve (P=.001). The
      distance from the sigmoid sinus to the mastoid portion of the facial nerve
      presents a positive linear relationship throughout its length (P< .001). The
      tympanic membrane presented a positional correlation with the distal portion of
      the facial nerve (P< .008). CONCLUSIONS: The mastoid portion of the facial nerve
      is proportional to reference structures in the temporal bone and this may help us
      to define measures prior to surgical otologic procedures.

PMID- 17498468
TI  - [Nasal leprosy: impact of multitherapy in the morphology and physiology of the
      nose].
AB  - INTRODUCTION: The multi-drug therapy protocol has allowed leprosy patients
      following this strategy to achieve complete recovery without developing
      neurotrophic sequelae or deformities. OBJECTIVES: To assess the impact of multi
      drug therapy on the development of nasal deformities and nasal airway patency.
      PATIENTS AND METHOD: In an overall group of 84 patients studied, 38 were treated
      with a therapy based on a single drug and 22 were treated with multi-drug while
      24 subjects formed a control group. Nose morphology was determined by anterior
      rhinoscopy. Nasal patency and flow resistances were measured by anterior
      rhinomanometry. The results were compared by using the Anova test for a single
      variable. RESULTS: The nasal structures in the group with therapy based on a
      single drug underwent resorption of bone and cartilage in the structures of the
      nose and increased flow resistance. In the group receiving the multi-drug
      protocol, there were no significant morphological alterations and nasal patency
      and flow resistance remained within normal levels. CONCLUSIONS: The multi-drug
      therapy is effective in preventing the development of nasal deformities and
      maintains normal nasal airflow.

PMID- 17498469
TI  - [Tracheotomy in children].
AB  - OBJECTIVE: To inspect and describe the results of tracheotomies carried out at
      our ENT Department and to assess changes in indications over the last few
      decades. MATERIAL AND METHODS: Retrospective study of 13 patients, aged 3 months
      to 14 years, admitted by the ENT Department to the Paediatric ICU at Puerta del
      Mar University Hospital for elective tracheotomy over a 92-month period. RESULTS:
      The main indication is shared by obstructive respiratory insufficiency, post
      surgery extubation failure and as a means of assisting ventilation in children
      requiring prolonged intubation. CONCLUSIONS: In the last 30 years the indications
      for paediatric tracheotomy have changed and the number of children needing
      intubation for more than 20-30 days has increased. It is no longer an emergency
      procedure to overcome a blockage in the upper airways but has instead become a
      technique for maintaining assisted ventilation for the medium to long term.

PMID- 17498470
TI  - [Characterization of the clinical evolution of nasopharyngeal carcinoma in
      Portuguese population].
AB  - OBJECTIVE: Characterization of the clinical evolution of nasopharyngeal cancer
      (NPC) patients in a Portuguese population during 31 years of follow-up. MATERIALS
      AND METHOD: Three hundred and twenty patients with epidermoid nasopharyngeal
      carcinoma were selected for this study. Histological subtypes were analyzed along
      with survival rates after different treatment schemes and according to AJCC and
      UICC staging classification systems. RESULTS: The most frequent histological
      subtype was undifferentiated nasopharyngeal carcinoma. The AJCC-2001 staging
      classification was considered the most suitable system for survival prediction.
      Better survival rates were found in patients treated with adjuvant chemotherapy
      (cisplatin and 5-fluorouracil) and these findings were similar to other published
      results. CONCLUSIONS: Although adjuvant chemotherapy may reduce the likelihood of
      distant metastasis, the latter is still the main cause of death in our study. The
      distant metastasis rate remains the crucial problem and bringing it down is an
      ever closer goal and a challenge for the future.

PMID- 17498472
TI  - [Posturographic examination of malingering patients].
AB  - INTRODUCTION: An aphysiological pattern in computerized dynamic posturography
      (CDP) may be produced by numerous causes. We analyze the results obtained in this
      test by a group of malingering patients. PATIENTS AND METHOD: This study analyzes
      a particular group of 7 malingerers, ie patients simulating a false and unreal
      equilibrium disorder, without any a priori awareness of the gain expected from a
      pathological report. The condition can only be identified with the very complex
      postural disorder known as "continuous imbalance." We analyze the results of the
      dynamic posturography test following the diagnostic criteria described by other
      authors. RESULTS: Of the criteria analyzed, we found Cevette's to be the most
      frequently positive for our study group. CONCLUSIONS: The wide diversity in the
      criteria used makes it necessary to apply them together, assuming a high level of
      suspicion and great care in the diagnostic process.

PMID- 17498471
TI  - [Cochlear implant in hypoacusis with alteration of connexin 26].
AB  - OBJECTIVE: The objective of this paper is to assess the benefits of cochlear
      implantation in a population of profound prelingual congenital deaf children with
      mutation of Connexin 26 (DFNB1 phenotype), compared with a population of profound
      congenital deaf children without mutation of this gene. PATIENTS AND METHOD: This
      retrospective study was carried out in 36 children with cochlear implants under
      the age of 6. All had profound congenital bilateral sensorineural hearing
      impairment, without cochlear malformation. Fifteen children were diagnosed as
      having DFNB1 and homozygous 30-35delG mutation, and 21 had no mutation of
      Connexin 26 (Cx26). All of them used Nucleus 24K or ST cochlear implants, with
      complete non-traumatic insertion of the electrodes, and follow-up was 12 months.
      RESULTS: There is no significant difference in pure tone audiometry and
      logoaudiometric tests between the 2 groups, children diagnosed as having DFNB1
      (homozygous 30-35delG mutation) and children without mutation of Cx26. However,
      the population with DFNB1 shows a tendency to achieve better results more quickly
      in vowels and bisyllabic word tests 12 months after implantation. CONCLUSIONS:
      The cochlear implant is an effective therapy for children with profound
      prelingual congenital hearing loss with mutation of Cx26.

PMID- 17498473
TI  - [Immunomediated inner ear disease: diagnostic validation by means of a systematic
      analysis of the scientific literature].
AB  - INTRODUCTION: Numerous tests have been developed to help in the diagnosis of the
      immunomediated inner ear disease (IMIED), although their usefulness is still the
      subject of some dispute. MATERIAL AND METHOD: Studies of cohorts of patients with
      suspected IMIED have been reviewed. A number of different serological tests were
      carried out and their response to immunosuppressive therapy was noted. RESULTS:
      After reviewing 790 articles, the studies analyzed present great heterogeneity in
      the clinical characteristics of the patients recruited (sudden deafness,
      fluctuating and rapidly progressive hearing loss, Meniere's disease), the
      inclusion and exclusion criteria, the delay between the diagnosis and the start
      of medical treatment or the response criteria. CONCLUSIONS: The diagnosis of
      IMIED is based on clinical presentation and response to corticosteroids. At
      present no test represents the gold standard in the diagnosis of IMIED. Serologic
      tests can support the diagnosis, but a methodologically more rigorous approach is
      needed to identify the true clinical importance of these tests for daily
      practice.

PMID- 17498474
TI  - [Lemierre's syndrome. An unusual variant].
AB  - Lemierre's syndrome or postanginal septicaemia is described in the literature as
      an unusual complication of oropharyngeal infection. In most cases the syndrome is
      caused by Fusobacterium necrophorum. This disease usually occurs in young healthy
      individuals with an oropharyngeal infection, implying high fever, cervical
      tumefaction, and cervical pain, frequently associated with septic lung
      embolization. This case report is an unusual variant of this disease in a 12-year
      old patient whose site of primary infection was the middle ear.

PMID- 17498475
TI  - [Total idiopathic laryngotracheal stenosis. Treatment with mitomycin C].
AB  - This case report involves a 69-year-old woman who presented idiopathic
      laryngotracheal stenosis with total obstruction of the airway. Seven surgical
      procedures involving open field and endoscopy techniques had to be performed due
      to repeated re-obstructions. The novelty in this case is that success was finally
      obtained with the use of mitomycin C. The drug action is well known, but is
      interesting to report a case in which success was only obtained when we used
      mitomycin C.

PMID- 17498476
TI  - [OK-432 therapy for cervicofacial lymphangioma in adults].
AB  - The treatment of cervicofacial lymphangiomas has been changing in recent years.
      OK-432 appears to be a relatively safe and effective treatment option for
      patients of all ages. An intracystic injection of OK-432 produces a local
      inflammatory reaction, leading to resolution of the lesion. Cosmetically, the
      outcome is excellent, leaving no lesions on the skin at the injection site,
      unlike other sclerosing agents. It may thus be considered as the treatment of
      choice, especially in cases where surgical treatment is associated with the
      possibility of serious functional or cosmetic side effects.

PMID- 17498477
TI  - [A review of international clinical trial registration].
AB  - Clinical trials play a critical role in medical research. However, only a few
      clinical trials conducted at present have been registered at various clinical
      trial registries. Clinical trial registration can prevent bias in these
      registered trials effectively and avoid unnecessary waste of resources due to
      meaningless repeats. Moreover, it will benefit the development of evidence-based
      medicine, and promote human welfare. Great attention has been paid to the
      importance and necessity of clinical trial registration. This review briefly
      introduced the definition, justification, contents, history, current status of
      clinical trial registration, and introduced the information regarding important
      international clinical trial registries in detail. Clinical trial registration
      should be developed toward a transparent, compulsory and comprehensive stage.

PMID- 17498478
TI  - [Expressions of epidermal growth factor receptor signaling substances in gastric
      mucosal cells influenced by serum derived from rats treated with
      electroacupuncture at stomach meridian acupoints].
AB  - OBJECTIVE: To study the effects of serum derived from rats treated with
      electroacupuncture at stomach meridian acupoints on the expressions of epidermal
      growth factor receptor (EGFR) signaling substances phospholipase C gamma-1 (PLC
      gamma-1), protein kinase C (PKC) and c-myc in gastric mucosal cells. METHODS:
      Sixty rats were randomly divided into normal group, stomach meridian group,
      gallbladder meridian group, stomach meridian plus PD153035 group and gallbladder
      meridian plus PD153035 group. Water-immersion and restrained stress methods were
      adopted for inducing gastric mucosal injury in the rats. Gastric mucosal cells
      were separated by using pronase digestion method, and incubated by PD153035, a
      EGFR inhibitor, and 100 ml/L serum. The expression of PLC gamma-1 in the gastric
      mucosal cells was tested by enzyme linked-immunosorbent assay (ELISA), while the
      expression of PKC by isotope incorporate assay and the expression of c-myc by
      reverse transcription polymerase chain reaction assay (RT-PCR). RESULTS: In
      gastric mucosal cells, weak expressions of PLC gamma-1, PKC and c-myc were seen
      in the normal group, and relatively strong expressions of PLC gamma-1, PKC and c
      myc were seen in the stomach meridian group and the gallbladder meridian group,
      among which, the expressions of PLC gamma-1, PKC and c-myc in the stomach
      meridian group were the strongest, and there was a significant difference between
      the stomach meridian group and the gallbladder meridian group (P<0.01). Relative
      weak expressions of PLC gamma-1, PKC and c-myc were seen in the stomach meridian
      plus PD153035 group and the gallbladder meridian plus PD153035 group, and there
      was a significant difference between the stomach meridian group and the stomach
      meridian plus PD153035 group (P<0.01). CONCLUSIONS: The serum derived from the
      rats treated with electroacupuncture at stomach meridian acupoints can activate
      the EGFR singling pathway, and this provides an evidence for the theory of
      "relative particularity between meridians and viscera" in traditional Chinese
      medicine.

PMID- 17498479
TI  - [Clinical trial registration system and evidence-based medicine].
AB  - The authors briefly introduced the management of clinical test for new drug
      development, clinical trials for drugs prepared in hospital and post-market
      drugs, and other types of clinical trials. The mechanism of WHO International
      Clinical Trial Register Platform (WHO ICTRP), Chinese Clinical Trial Register
      (ChiCTR) and Chinese Clinical Trial Registration and Publishing Collaboration
      (ChiCTRPC) were also introduced. The authors suggested the trialists to practice
      the basic philosophy of evidence-based medicine as the rules of their thought and
      action, and considered that this is the inner guarantee system for the validity
      of clinical trials.

PMID- 17498480
TI  - [Case recruitment in large-scale clinical trials of traditional Chinese
      medicine].
AB  - Case recruitment of large-scale clinical trials should be strictly checked in
      quality and quantity for it is the key to clinical trial. This study discusses
      the main difficulties and countermeasures in the case recruitment of large
      sample, multi-center clinical trials according to the national research project
      "Myocardial Infarction Secondary Prevention Study in Traditional Chinese
      Medicine".

PMID- 17498482
TI  - [Potential of using pattern diagnosis of traditional Chinese medicine to improve
      the clinical use of antihypertensive agents].
AB  - Despite the availability of six classes of antihypertensive agents, control of
      blood pressure and improving patients' quality of life remain far from ideal.
      There is a wide variability in terms of the hypotensive effect and side effect
      profile for the same antihypertensive agent used in different patients. How to
      select the right agent to provide the most beneficial results in terms of
      efficacy and improvement of quality of life as well as to decrease clinical
      symptoms and minimize adverse reactions is an important therapeutic challenge. It
      has been suggested that clinical usage of pattern (Zheng) diagnosis of
      traditional Chinese medicine may improve the accuracy in selecting the right
      antihypertensive agents with improved efficacy and deceased adverse effects.
      Limited research in this area suggested the calcium channel blocker may work
      better in treating phlegmatic damp excess pattern and blood stasis pattern while
      beta-blockers may be more beneficial in the liver yang rising pattern. On the
      other hand, angiotensin converting enzyme inhibitors may be more suitable in a
      yin deficiency and yang hyperactivity pattern as well as combined liver and
      kidney yin deficiency pattern. More research studies using this innovative
      approach in improving the selection of antihypertensive agents including
      mechanistic studies are urgently needed.

PMID- 17498481
TI  - [Treatment of Alzheimer disease: an evidence-based review].
AB  - OBJECTIVE: The purpose of this research was mainly two-fold: first, to get an
      understanding of current researches conducted on Alzheimer disease in China;
      second, to systematically evaluate and compare Alzheimer's treatment delivered by
      traditional Chinese medicine (TCM) and Western medicine. METHODS: Two steps were
      employed in this research. They were data collection and cleaning, followed by
      systemic review and qualitative analysis. The data were selected from the
      following two databases: CNKI (http://www.cnki.net) and Wanfang Data
      (http://www.wanfangdata.com.cn). Inclusion criteria were: (1) Chinese literature;
      (2) Published between year 1994 and year 2004; (3) Using TCM as treatment and
      Western medicine as control; (4) Similar research purposes and methodology; (5)
      Subjects were diagnosed as Alzheimer disease. Descriptive analysis, homogeneity
      test, meta analysis, sensitivity analysis and subgroup analysis were performed in
      the second step. RESULTS: Supposing all qualified studies were of high quality,
      we got the following conclusion: the advantage of TCM was losing because of the
      newly-developed acetylcholinesterase inhibitors came in market. Moreover, the
      studies conducted after year 2002 were more homogeneous in comparison with those
      conducted in early years. Those studies using mini-mental status examination
      (MMSE) as outcome measurement were also more homogeneous than non-MMSE
      measurement groups. Combined odds ratio in comparative studies was 1.5 fold
      higher than that in experimental studies. Regarding to different outcome
      measurement, those studies using TCM assessment profile were 2.58(4.79/1.86) fold
      higher than those using MMSE as outcome measurement. CONCLUSIONS: After systemic
      literature search, we found that only 40 out of 2,403 studies met our inclusion
      criteria. Moreover, those qualified studies were of low quality. Therefore, the
      external validity of this study would be compromised. The solution to this would
      be to improve study quality by strengthening study design and carefully select
      more homogeneous subjects in terms of syndrome differentiation, by so doing, the
      results of meta analysis will be more convincing and easily recognized by
      international society.

PMID- 17498483
TI  - [Pathogenesis and prevention tactics of aspirin resistance].
AB  - Aspirin (acetylsalicylic acid) is a nonsteroidal anti-inflammatory drug. Despite
      its wide uses for more than 100 years, knowledge about mechanism of action and
      therapeutic issues of aspirin are still under discussion. The use of aspirin has
      been changed from an analgesic, anti-pyretic and anti-inflammatory agent to an
      anti-thrombotic agent, especially in secondary prevention of cardiovascular
      events. Aspirin has reduced the risk of cardiovascular events by 25%. However,
      the phenomenon of "aspirin resistance" has been described that in 5%-60% of
      patients aspirin may not achieve adequate efficacy of suppressing platelet
      activity. The convinced causes of this phenomenon are still unknown. It is
      probably due to drugs interaction, inadequate dosage and so on. By far the
      existing studies of aspirin are insufficient to explain all phenomena of aspirin
      resistance. And the results are not always uniform about the same research.
      Therefore, the characteristics in different population with aspirin resistance
      may account for the complexity. It is unrealistic to elucidate all aspirin
      resistance by only one pathway. More studies are required to investigate the
      mechanisms in different population respectively. According to the theory of
      traditional Chinese medicine and the trait of cardiovascular disease, which often
      relapses and has a long history, aspirin resistance should be considered as
      collaterals disease. It can be treated with aspirin and traditional Chinese drugs
      which have the power to strengthen body resistance, reduce phlegm, remove blood
      stasis and toxic materials from meridians. The problem of aspirin resistance
      might be solved by this way, because the traditional Chinese medicine has the
      superiority of selecting appropriate therapeutic methods based on syndrome
      differentiation for different population and regulating the whole body's
      function. Subsequently, cardiovascular disease might be effectively prevented.

PMID- 17498484
TI  - [Clinical research of Yiqi Sanju Formula in treating central obese men at high
      risk of metabolic syndrome].
AB  - OBJECTIVE: To observe the therapeutic effects of Yiqi Sanju Formula (YQSJF), a
      compound Chinese herbal medicine, on central obese men at high risk of metabolic
      syndrome (MS). METHODS: Compared with 30 healthy male volunteers, 45 central
      obese men were separated randomly into two groups and received the interventions
      with YQSJF and placebo respectively for 10 weeks. Baseline characteristics,
      insulin resistance, inflammation cytokines and plasminogen activator inhibitor-1
      (PAI-1) and tissue plasminogen activator (t-PA) were evaluated before and after
      treatment. RESULTS: The score of homeostatic model assessment for insulin
      resistance (HOMA-IR) and the levels of C reactive protein (CRP), free fatty acid
      (FFA) and PAI-1 in obese men were higher than those in the control group, while t
      PA was lower. After treatment, compared with placebo group, body mass index,
      waist, and waist-to-hip ratio were decreased significantly in subjects who
      received YQSJF (P<0.01). The score of HOMA-IR and the levels of CRP, FFA and PAI
      1 were decreased significantly, and the level of t-PA was increased significantly
      (P<0.01). CONCLUSION: YQSJF can reduce obesity and insulin resistance in central
      obese men at high risk of MS and improve inflammation and fibrinolysis, which
      indicates that it can reduce the risk of atherosclerosis.

PMID- 17498485
TI  - [Clinical study on 100 cases of severe acute pancreatitis in aged patients].
AB  - OBJECTIVE: To analyze the clinical features of severe acute pancreatitis (SAP) in
      aged patients, and to explore the measures of its diagnosis and treatment.
      METHODS: The clinical data of 100 aged patients (55-85 years old) with SAP
      admitted from January 2003 to December 2005 were reviewed and compared with those
      of 221 non-aged SAP patients (11-54 years old) admitted at the same period.
      RESULTS: Totally 112 times of onset occurred in 100 aged patients, and the main
      causes for senile SAP were biliary diseases and hyperlipemia. Both acute
      physiology and chronic health evaluation II (APACHE II) and Ranson scores of the
      aged patients with SAP were higher than those of the control group (P<0.05);
      while there was no significant difference in Balthazar score between the two
      groups(P>0.05). The incidences of low serum calcium, low albumin and high
      aspartate aminotransferase (P<0.05), liver, kidney or brain impairment as well as
      the mortality were higher in the senile SAP group than those in the control group
      (P<0.05). CONCLUSIONS: Biliary disease and hyperlipemia are the main causes of
      senile SAP, which lacks characteristic clinical symptoms and is often associated
      with multiple complications such as infection and lung, gastrointestinal tract,
      liver, kidney, and brain impairment. Individualized differential treatment with
      integrated traditional Chinese and Western medicine based on stage classification
      is an effective approach.

PMID- 17498486
TI  - [Effect of intravenous drip infusion of cyclophosphamide with high-dose
      Astragalus injection in treating lupus nephritis].
AB  - OBJECTIVE: To observe the effect of high-dose Astragalus injection and
      cyclophosphamide (CTX) on infection, urine protein and immune function of the
      patients with lupus nephritis. METHODS: Forty-three patients diagnosed as
      systemic lupus erythematosus (SLE) complicated by kidney damage and qi-deficiency
      syndrome were randomly divided into trial group (n=23) and control group (n=20).
      Patients in both groups were treated for 3 months. Intravenous drip infusion of
      0.8 g CTX was administered to all patients once a month, while intravenous drip
      infusion of 20 ml Astragalus injection was only administered to patients in the
      trial group every day for 12 days in each month. RESULTS: The decrease of active
      clinical symptom score after the treatment in the trial group was greater than
      that in the control group (P<0.05). The infection rates of the trial group and
      the control group were 4.35% and 25% respectively. The decrease of 24-hour urine
      protein and CD8, and the increase of red blood cell count and serum albumin in
      the trial group were greater than those in the control group, and there were
      significant differences between the two groups (P<0.05). White blood cell count
      in the trial group was decreased less than that in the control group after the
      treatment (P<0.05). CONCLUSION: High-dose Astragalus injection used together with
      CTX is more effective than CTX alone in decreasing infection rate and urine
      protein and improving immune function for patients with lupus nephritis.

PMID- 17498487
TI  - [Effect evaluation for comprehensive treatment of acute stage of stroke].
AB  - OBJECTIVE: To explore the clinical evaluation system reflecting the superiority
      and characteristics of comprehensive traditional Chinese medicine (TCM) therapy
      for acute stroke. METHODS: A randomized controlled trial with single blind in
      various therapeutic centers was applied on the patients with the acute stage of
      hemorrhagic stroke due to hypertension, who were allocated to the trial group and
      the control group. The trial group accepted the general Western medicine therapy
      and differential treatment of traditional Chinese medicine based on stage
      classification. Patients in the control group were treated with the general
      Western medicine and the placebo of traditional Chinese herbal medicine. The
      treatment effect was assessed at the 7th day, 14th day, 21st day, and 28th day of
      post-treatment and after 3-month follow-up. The clinical evaluation system
      included the syndromes of TCM (ZH), Glasgow coma standard (GCS), nerve functional
      failure (NF), activity of daily living (ADL), Barther index (BI), quality of life
      index (QLI) and functional activities questionnaire (FAQ). RESULTS: Four hundred
      and four patients with acute stroke were included. There were 178 cases with yang
      syndrome and 21 cases with yin-syndrome in the trial group (n=199), and there
      were 165 cases with yang-syndrome and 40 cases with yin-syndrome in the control
      group (n=205). The rates of recovery and obvious improvement after 3-month
      treatment in the trial group and the control group were 86.5% and 73.6%
      respectively. There was significant difference between the two groups (P<0.01).
      The response sensitivity of the effect items indicated that the sensitivity of
      GCS began to increase from the 7th day and was high at the 14th day and the 21st
      day for all patients. The response sensitivity of the NF scale was high for all
      patients at the 14th day, the 21st day and the 28th day. The BI scale and the QLI
      scale were sensitive to the patients with light and middle stage of stroke at the
      21st day, and were sensitive to the patients with light stage of stroke after 3
      month follow-up. The FAQ scale was sensitive to the light stroke at the 21st day
      and after 3-month follow-up. The ADL scale was sensitive to all patients at the
      28th day and the patients with light stage of stroke after 3-month follow-up. The
      ZH scale was sensitive to all patients from 0 to 7d, the 14th day, and the 28th
      day. The principle components analysis indicated these 7 items could reflect the
      condition of stroke from 0-7d, the 21st day and after 3-month follow-up, and
      could be used to evaluate the therapeutic effect of hemorrhagic stroke. ZH scale
      and FAQ scale were more sensitive than other effect items at the 28th day.
      CONCLUSION: The seven items (GCSbNFbBIbQLIbFAQbADLbZH) have high sensibility to
      all patients in the acute stage of hemorrhage stroke especially at the 21st day.
      The ZH score will change in accord with the condition of stroke, and is
      appropriate to reflect the condition of stroke. It is believed that the seven
      items can form the system of effect evaluation in different stages of stroke, and
      the ZH scale is a very important item.

PMID- 17498488
TI  - [Tripterine inhibits all-trans retinoic acid-caused adhesion between leukemia
      cells and endothelial cells].
AB  - OBJECTIVE: Increasing of adhesion between leukemia cells and endothelial cells
      during all-trans retinoic acid (ATRA) treatment plays an important role in
      retinoic acid syndrome. This work observed the effects of tripterine on this ATRA
      caused increasing in adhesion. METHODS: The effects of tripterine on ATRA-induced
      expressions of adhesive molecules in acute promyelocytic leukemia cell line NB4
      and human umbilical vascular endothelial cells (HUVEC) were detected by flow
      cytometry. The effects of tripterine on adhesion between ATRA-treated NB4 and
      HUVEC were determined by adhesive assays. RESULTS: ATRA caused remarkable
      elevation of intercellular adhesion molecule-1 (ICAM-1) in NB4 cells, which could
      be significantly reduced by tripterine (P<0.01). The expressions of E-selectin,
      vascular cell adhesion molecule-1 (VCAM-1) and ICAM-1 in HUVEC were elevated by
      conditioned medium from ATRA-induced NB4 (ATRA-NB4-CM) (P<0.01), and inhibited by
      tripterine with inhibition rates being 25.3%, 42.4% and 61.0% respectively. ATRA
      increased the adhesion between NB4 and HUVEC, which was reversed completely by
      tripterine. CONCLUSION: Tripterine can inhibit ATRA-caused adhesion between
      leukemia cells and endothelial cells, and it might be a potential agent for
      treating retinoic acid syndrome.

PMID- 17498489
TI  - [Effects of Chinese herbal recipe Weichang'an in inducing apoptosis and related
      gene expression in human gastric cancer grafted onto nude mice].
AB  - OBJECTIVE: To investigate the mechanism of Chinese herbal recipe Weichang'an
      (WCA) in inducing cell apoptosis of human gastric cancer grafted onto nude mice.
      METHODS: The high performance liquid chromatography was used for monitoring the
      stability of WCA. A human gastric cancer cell line SGC-7901 grafted in nude mouse
      was used as the animal model. The mice were divided into untreated group and two
      experimental groups. Animals in the two experimental groups received either WCA
      over a 34-day period or 5-fluorouracil (5-FU) over a 6-day period starting at the
      8th day after grafting. Animals in the untreated group received normal saline on
      an identical schedule. Animals were killed 41 days after being grafted. To assess
      the effect of the treatment on tumor, the tumor weight was determined by the
      electron balance immediately after the animals were killed. SP
      immunohistochemical method was used to detect the expression of proliferating
      cell nuclear antigen (PCNA) in grafts. Apoptotic indices (AI) of the tumor cells
      were examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate fluorescence nick end labeling (TUNEL) method. SP method was also
      used to detect the expressions of cleaved caspase-3, caspase-8 and caspase-9.
      SYBR green dye I real-time quantitative polymerase chain reaction (real-time
      quantitative [corrected] PCR) was used to assess the related gene alterations in
      mRNA level. The expressions of phospho-Stat3 (Tyr705) and bcl-2 proteins were
      detected by using SP method. RESULTS: Compared with the untreated group, tumor
      growth was significantly inhibited by treatment of WCA or 5-FU (P<0.01,
      respectively). The tumor inhibition rate in the WCA-treated group was 48.70% and
      that in the 5-FU-treated group was 60.10%. The average labeling index (LI) for
      PCNA in the WCA-treated group and 5-FU-treated group was significantly decreased
      as compared with that in the untreated group, respectively. The AI of human
      gastric cancer grafted in the nude mice detected by using TUNEL method was
      significantly increased to (9.72+/-4.51)% in the WCA-treated group, while it was
      (2.45+/-1.37)% in the untreated group. 5-FU-treated group was also found a
      significantly increased AI compared with the untreated group. The expressions of
      cleaved caspase-3 and caspase-9 in the WCA-treated group and 5-FU-treated group
      were significantly increased as compared with those in the untreated group. But
      caspase-8 showed no significant alteration either in the WCA-treated group or in
      the 5-FU-treated group. The expression levels of Stat3 (2(-)delta delta
      C(T))=0.16) and bcl-2 (2(-)delta delta C(T))=0.10) detected by using real-time
      quantitative [corrected] PCR were lower in the WCA-treated group than those in
      the untreated group. The expressions of phospho-Stat3 (Tyr705) and bcl-2 in the
      WCA-treated group were significantly decreased as compared with those in the
      untreated group. CONCLUSIONS: Chinese herbal recipe WCA can inhibit gastric
      cancer cell SGC-7901 growth in vivo, induce gastric cancer cell apoptosis and
      suppress the cell proliferation. WCA induces apoptosis through the caspase-9 and
      caspase-3 pathway in vivo. Its mechanism might be involved in the down-regulation
      of Stat3 and bcl-2 genes.

PMID- 17498490
TI  - [Effects of NK-104 on apoptosis and caspase-3 activity in hepatocellular
      carcinoma cells].
AB  - OBJECTIVE: To study the apoptosis of human hepatocellular carcinoma cell line
      HepG 2 induced by pitavastatin (NK-104) and to investigate the change of caspase
      3 activity. METHODS: HepG 2 cells were treated with NK-104 for 48 hours and
      observed under a microscope by using Hoechst 33258 staining. The proliferation of
      the cells was detected with WST-8 method. The apoptosis peaks were examined by
      flow cytometry. The caspase-3 activity was detected with caspase-3 colorimetric
      protease assay. RESULTS: The treatment of HepG 2 with 10 micromol/L NK-104 could
      inhibit the proliferation, and induce HepG 2 apoptosis and up-regulate the
      caspase-3 activity. CONCLUSION: NK-104 at 10 micromol/L induces apoptosis of HepG
      2 cells. It is dependent on caspase-3 pathway in human hepatocellular carcinoma
      cells.

PMID- 17498491
TI  - [Effects of Jianpi Huoxue Decoction on Kupffer cell signal pathway activation in
      rats with liver injury induced by Lieber-Decarli liquid diet and
      lipopolysaccharide].
AB  - OBJECTIVE: To observe the effects of Jianpi Huoxue Decoction, a compound Chinese
      herbal medicine, on Kupffer cell signal pathway activation in rats with liver
      injury induced by Lieber-Decarli liquid diet and lipopolysaccharide (LPS).
      METHODS: SD rats were divided into normal, control liquid diet, ethanol liquid
      diet and ethanol liquid diet plus Jianpi Huoxue Decoction group. Rats were
      administrated with Jianpi Huoxue Decoction or distilled water via gastrogavage
      for 4 weeks after administration with ethanol or control liquid diet for 2 weeks
      respectively. After that, rats in each group were stimulated with LPS via
      gastrogavage for 3.5 h and harvested. Alanine aminotransferase (ALT) in serum and
      triglyceride (TG) in liver were analyzed. Pathological changes in liver tissues
      were observed in HE staining section. Tumor necrosis factor-alpha(TNF-alpha) in
      portal vein plasma was assayed by ELISA. The protein expressions of CD68, Toll
      like receptor 4 (TLR4), phosphorylation-I kappa B (P-I kappa B) and TNF-alpha in
      liver were evaluated with Western-blotting. RESULTS: After the treatment with
      Jianpi Huoxue Decoction, the pathologic changes in liver tissue were lightened,
      levels of ALT in serum, TG in liver and TNF-alpha in portal vein plasma were
      decreased, and the protein expressions of CD68, TLR4, P-IkappaB and TNF-alpha in
      liver were reduced. CONCLUSION: Jianpi Huoxue Decoction can inhibit Kupffer cell
      signal pathway activation in rats with liver injury induced by Lieber-Decarli
      liquid diet and LPS.

PMID- 17498492
TI  - [Metabonomic study of syndrome of liver qi stagnation and spleen deficiency in
      rats].
AB  - OBJECTIVE: To determine the changes of the plasma metabolic phenotype in rats
      with chronic restraint stress (rats with syndrome of liver qi stagnation and
      spleen deficiency), so as to reveal the biological features of the syndrome of
      liver qi stagnation and spleen deficiency, and to examine potential application
      of metabonomic analysis in studies of syndromes in traditional Chinese medicine.
      METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into four
      groups: group A, 7 d normal control group; group B, 21 d normal control group;
      group C, 7 d stress group; and group D, 21 d stress group, with 6 rats in each
      group. Chronic restraint was used to induce stress in rats. Blood was collected
      from the cardio-ventricle under anesthesia on the 8th (groups A and C) or 22nd
      day (groups B and D) and detected by using the Fourier variable superconducting
      nuclear magnetic resonance (NMR) spectrometer (Varian UnityInova 600 M). Free
      induction decay signals were transferred into one-dimensional NMR spectrogram via
      32 k Fourier transformation. Segmental integral calculus (0.04 ppm per segment)
      was performed from 4.5-0.5 ppm (Carr-Purcell-Meiboom-Gill, CPMG) or 6.0-0 ppm
      (longitudinal eddy-delay, LED) as defaulted 1H spectra values by using the VNMR
      software. Data were saved as text or excel files after normalization and then
      used for pattern recognition analyses. All the data were analyzed by principal
      component analysis (PCA) using the SIMCA-P 10.0 software (Umetrics AB, Umea,
      Sweden). RESULTS: The PCA analysis of rat plasma (1)H NMR spectra revealed
      different metabolic spectra between stress and control groups, which were
      consistent with alterations of in vivo metabolisms in rats under stress stimuli.
      Compared with the normal control group, rats with repeated stress displayed
      significant changes in spectral peak shapes of acetate, lactate, tyrosine, low
      density lipoprotein, and unknown compounds (3.44 ppm). These altered metabolites
      can be used as biomarkers of syndrome of liver qi stagnation and spleen
      deficiency for further studies. CONCLUSION: The (1)H NMR spectra of metabolites
      in the rat blood are differentially changed after chronic stress. Specific,
      characteristic metabolic products can be identified by analyses of metabonomics,
      which lead to interpretation of biological feature of Chinese medicine syndromes.
      Therefore, metabonomic analysis is an approach with good development prospects to
      studies of TCM syndromes.

PMID- 17498493
TI  - [Preparation of nano-liposome enveloping Flos Magnoliae volatile oil].
AB  - OBJECTIVE: To discuss the influences of the concentrations of sodium cholate,
      cholesterol and drug, preparation temperature, ultrasonic time and power on the
      particle size and encapsulation efficiency of Flos Magnoliae volatile oil nano
      liposome through film-ultrasonic wave technique together with membrane filter
      method. METHODS: The nano-liposomes were prepared by film-ultrasonic wave
      technique together with membrane filter method. The drug content in liposomes was
      determined by gas chromatography and the particle size was determined by laser
      light scattering granularity equipment. RESULTS: By film-ultrasonic wave
      technique together with membrane filter method, the liposomes in the range of 30
      40 nm were prepared. The prepared nano-liposomes demonstrated good
      decentralization and homogeneity, and the encapsulation efficiency was (91.7+/
      3)%. CONCLUSION: Film-ultrasonic wave together with membrane filter method is a
      simple method to fabricate nano-magnoliae liposome.

PMID- 17498494
TI  - [Th cell differentiation in chronic stage of viral myocarditis in mice and
      interference of Qingxin-II Recipe].
AB  - OBJECTIVE: To investigate part mechanisms of Th cell differentiation, and to
      observe the interference effect of Qingxin-II Recipe in the chronic stage of
      viral myocarditis (VMC), so as to provide some experimental evidences for
      illuminating the pathogenesis of VMC and treatment mechanisms of Qingxin-II
      Recipe. METHODS: According to 20%-40% death rate of experiment in advance, 100
      BALB/c male mice (4 weeks old and weighing 12-15 g) were used. Twenty mice were
      randomly assigned to normal control group, and the other 80 mice were
      intraperitoneally injected with 0.1 ml normal saline containing coxsackie virus
      B3 at the 1st, 4th and 28th day (the virus densities were 1:2000, 1:1000 and
      1:500 respectively) to induce chronic VMC. At the 42nd day, the surviving mice
      were randomly divided into untreated group and treatment group, with 20 mice in
      each group. Mice in the treatment group were orally administered with 0.2 ml
      Qingxin-II Recipe every day, while mice in the normal control group and the
      untreated group were administered with 0.2 ml normal saline. All the mice were
      sacrificed after 45 days, and the sera, heart and spleen cells were collected.
      Then the myocardial pathological changes were observed by using a light
      microscope, and the levels of IL-4, IL-10 and IFN-gamma in serum were detected by
      enzyme linked immunosorbent assay (ELISA). And the Th cell differentiation was
      observed by flow cytometry. RESULTS: No obvious myocardial pathological changes
      were observed in mice of the normal control group. Myocardial pathological
      changes in the treatment group were slighter than those in the untreated group.
      The difference of serum IL-10 level between the normal control group and the
      untreated group showed no significance (P>0.05), and the levels of IFN-gamma and
      IL-4 of the untreated group were higher than those of the normal control group
      (P<0.05 or P<0.01). There was no statistical difference in IL-10 level between
      the treatment group and the untreated group (P>0.05), while the serum levels of
      IL-4 and IFN-gamma of the treatment group were lower than those of the untreated
      group (P<0.05 or P<0.01). There was no significant difference of the Th1 cell
      responder between the treatment group and the untreated group (P>0.05), while the
      Th2 cell responder was inhibited significantly in the treatment group (P<0.05).
      CONCLUSION: Qingxin-II Recipe can restore the balance of Thl and Th2 cells
      through inhibiting the reaction of Th2.

PMID- 17498495
TI  - [Ganoderma spores may regulate the levels of mitochondria-related molecular
      substances in hippocampus of young rats birthed by rats with gestational
      hypertension].
AB  - OBJECTIVE: To investigate the effects of Ganoderma spores on mitochondria-related
      molecular substances in hippocampus of young rats birthed by rats with
      gestational hypertension. METHODS: Nitric oxide synthase (NOS) inhibitor Nw-nitro
      L-arginine methylester (L-NAME) was intraperitoneally injected into pregnant rats
      to induce gestational hypertension, and Ganoderma spores were administered
      orally. The effects of Ganoderma spores on levels of mitochondria-related
      molecular substances in hippocampus of young rats birthed by the rats with
      gestational hypertension were evaluated with immunoradiometric assay of cAMP, RT
      PCR analysis of related genes, and detection of enzyme activity. RESULTS: In
      hippocampus of the new-born rats birthed by rats with gestational hypertension,
      the cAMP level, mitochondrial DNA (mtDNA) level and adenosine triphosphatase
      (ATPase) activity were decreased, and the expression level of peroxisome
      proliferator activated receptor gamma coactivator 1 alpha (pgc1 alpha) was
      unchanged compared to the normal control group. The cAMP level, mtDNA level,
      ATPase activity and pgc1 alpha expression level in hippocampus of 30-day post
      natal rats were lower than those of the rats in normal control group. After oral
      administration of Ganoderma spores, the cAMP and mtDNA levels in hippocampus of
      the new-born rats and 30-day post-natal rats recovered almost to the levels of
      normal control rats, and the ATPase activity and pgc1 alpha expression level were
      also increased significantly. CONCLUSION: Ganoderma spores may regulate the
      levels of mitochondria-related molecular substances in hippocampus of young rats
      birthed by rats with gestational hypertension.

PMID- 17498496
TI  - [Effects of Panax notoginseng saponins on mRNA expressions of interleukin-1 beta,
      its correlative factors and cysteinyl-aspartate specific protease after cerebral
      ischemia-reperfusion in rats].
AB  - OBJECTIVE: To investigate the effects of Panax notoginseng saponins (PNS) on mRNA
      expressions of interleukin-1 beta (IL-1 beta), interleukin-1 receptor type I (IL
      1RI), interleukin-1 receptor antagonist (IL-1ra), intercellular adhesion molecule
      1 (ICAM-1), cysteinyl-aspartate specific protease-1 (caspase-1), caspase-3 and
      caspase-8 after cerebral ischemia-reperfusion in rats. METHODS: Focal cerebral
      ischemia reperfusion in rats was induced by the method of nylon monofilament via
      the internal carotid artery. PNS was administered intraperitoneally respectively
      five minutes before cerebral ischemia and twelve hours after cerebral ischemia.
      After cerebral ischemia for two hours followed by reperfusion for twenty two
      hours, the mRNA expressions of IL-1 beta, IL-1RI, IL-1ra, ICAM-1, caspase-1,
      caspase-3 and caspase-8 in brain tissue were determined by reverse transcription
      polymerase chain reaction assay. RESULTS: After cerebral ischemia for two hours
      followed by reperfusion for twenty two hours, the mRNA expression levels of IL-1
      beta, IL-1RI, IL-1ra, ICAM-1, caspase-1, caspase-3 and caspase-8 in brain tissue
      in the untreated group were obviously elevated as compared to those in the sham
      operation group (P<0.05 or P<0.01). The mRNA expression levels of IL-1 beta, IL
      1RI, IL-1ra in brain tissue in the PNS group were lower than those in the
      untreated group, but higher than those in the sham-operation group, and without
      statistical differences as compared to those in the sham-operation group and in
      the untreated group (P>0.05). The mRNA expression level of caspase-3 in brain
      tissue in the PNS group was significantly lower than that in the untreated group
      (P<0.05), but PNS had no effect on the mRNA expression levels of ICAM-1, caspase
      1 and caspase-8 in brain tissue. CONCLUSION: PNS can inhibit the mRNA expression
      of caspase-3, slightly inhibit the mRNA expressions of IL-1 beta and its
      correlative inflammatory factors in brain tissue. The protective effects of PNS
      on cerebral injury induced by ischemia-reperfusion may be related to inhibiting
      the mRNA expressions of caspase-3, IL-1 beta and its correlative inflammatory
      factors in brain tissue.

PMID- 17498497
TI  - [High-protein diet and high-grade proteinuria aggravate the progression of
      chronic renal failure in rats].
AB  - OBJECTIVE: To study the effects of high-protein diet (HPD) and high-grade
      proteinuria in aggravating the progression of chronic renal failure (CRF) in
      rats. METHODS: CRF with high-grade proteinuria was induced by supplying HPD in
      five sixth nephrectomy rats, and the changes of serum creatinine (Scr), blood
      urea nitrogen (BUN), endothelin-1 (ET-1), thromboxane B(2) (TXB(2)) and 6-keto
      prostaglandin F(l alpha) (6-Keto-PGF(l alpha)) were observed. At the same time,
      the content of malondialdehyde (MDA), and the activities of glutathione
      peroxidase (GSH-Px) and superoxide dismutase(SOD)were measured in blood and renal
      tissue of the rats. RESULT: HPD and high-grade proteinuria could accelerate the
      damage of kidney through increasing the levels of ET-1 and TXB(2), reducing the
      level of 6-Keto-PGF(l alpha), and attenuating the activities of SOD and GSH-Px.
      CONCLUSION: HPD can accelerate the damage of kidney through inducing the high
      grade proteinuria in five sixth nephrectomy rats, influencing the expression of
      kidney vasoactive substance, and reducing the anti-oxidation.

PMID- 17498498
TI  - [Clinical observation of treatment of alcoholic fatty liver by Gehua Jiejiu
      Xiaozhi Decoction].

PMID- 17498499
TI  - [Treatment of anaphylactoid purpura in children: a report of 65 cases].

PMID- 17498500
TI  - Chemical components of Centella asiatica and their bioactivities.

PMID- 17498501
TI  - [Discrimination and interpretation of errors of statistical expression and
      description in medical dissertations].

PMID- 17498502
TI  - [Sentence structure in English translation of traditional Chinese medicine].

PMID- 17498503
TI  - [Brief comments on the English translation of a drug direction].

PMID- 17498504
TI  - Obesity: much silence makes a mighty noise.

PMID- 17498505
TI  - The epidemiology of obesity.
AB  - In the United States, obesity among adults and overweight among children and
      adolescents have increased markedly since 1980. Among adults, obesity is defined
      as a body mass index of 30 or greater. Among children and adolescents, overweight
      is defined as a body mass index for age at or above the 95th percentile of a
      specified reference population. In 2003-2004, 32.9% of adults 20-74 years old
      were obese and more than 17% of teenagers (age, 12-19 y) were overweight. Obesity
      varies by age and sex, and by race-ethnic group among adult women. A higher body
      weight is associated with an increased incidence of a number of conditions,
      including diabetes mellitus, cardiovascular disease, and nonalcoholic fatty liver
      disease, and with an increased risk of disability. Obesity is associated with a
      modestly increased risk of all-cause mortality. However, the net effect of
      overweight and obesity on morbidity and mortality is difficult to quantify. It is
      likely that a gene-environment interaction, in which genetically susceptible
      individuals respond to an environment with increased availability of palatable
      energy-dense foods and reduced opportunities for energy expenditure, contributes
      to the current high prevalence of obesity. Evidence suggests that even without
      reaching an ideal weight, a moderate amount of weight loss can be beneficial in
      terms of reducing levels of some risk factors, such as blood pressure. Many
      studies of dietary and behavioral treatments, however, have shown that
      maintenance of weight loss is difficult. The social and economic costs of obesity
      and of attempts to prevent or to treat obesity are high.

PMID- 17498506
TI  - The adipocyte as an active participant in energy balance and metabolism.
AB  - Obesity is responsible for the mounting incidence of metabolic disease in adult
      and pediatric populations. Understanding of the pathogenesis and maintenance of
      the obese state has advanced rapidly over the past 10 years. Bodily energy
      reserves are managed actively by complex systems that regulate food intake,
      substrate partitioning, and energy expenditure. An underlying assumption that
      circulating factors released from storage organs were able to signal bodily
      energy reserves was confirmed with the discovery of the leptin system. This proof
      of concept has spurred on the discovery of a multitude of other adipocyte
      generated factors. These circulating factors signal to the brain and other organs
      of metabolic importance, including adipose tissue, liver, muscle, and the immune
      system. Adipose-derived factors have numerous implications for the basic biology
      of obesity and provide prospective targets for the amelioration of obesity and
      its adverse metabolic consequences. In this review we detail the current
      understanding of leptin as a prototypical adipose tissue-derived hormone related
      to appetite and obesity. We also describe other important adipose-derived factors
      in relation to their metabolic effect.

PMID- 17498507
TI  - Gut hormones and appetite control.
AB  - Many peptides are synthesized and released from the gastrointestinal tract.
      Although their roles in the regulation of gastrointestinal function have been
      known for some time, it is now evident that they also physiologically influence
      eating behavior. Our understanding of how neurohormonal gut-brain signaling
      regulates energy homeostasis has advanced significantly in recent years. Ghrelin
      is an orexigenic peptide produced by the stomach, which appears to act as a meal
      initiator. Satiety signals derived from the intestine and pancreas include
      peptide YY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomodulin, and
      cholecystokinin. Recent research suggests that gut hormones can be manipulated to
      regulate energy balance in humans, and that obese subjects retain sensitivity to
      the actions of gut hormones. Gut hormone-based therapies may thus provide an
      effective and well-tolerated treatment for obesity.

PMID- 17498508
TI  - Biology of incretins: GLP-1 and GIP.
AB  - This review focuses on the mechanisms regulating the synthesis, secretion,
      biological actions, and therapeutic relevance of the incretin peptides glucose
      dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
      The published literature was reviewed, with emphasis on recent advances in our
      understanding of the biology of GIP and GLP-1. GIP and GLP-1 are both secreted
      within minutes of nutrient ingestion and facilitate the rapid disposal of
      ingested nutrients. Both peptides share common actions on islet beta-cells acting
      through structurally distinct yet related receptors. Incretin-receptor activation
      leads to glucose-dependent insulin secretion, induction of beta-cell
      proliferation, and enhanced resistance to apoptosis. GIP also promotes energy
      storage via direct actions on adipose tissue, and enhances bone formation via
      stimulation of osteoblast proliferation and inhibition of apoptosis. In contrast,
      GLP-1 exerts glucoregulatory actions via slowing of gastric emptying and glucose
      dependent inhibition of glucagon secretion. GLP-1 also promotes satiety and
      sustained GLP-1-receptor activation is associated with weight loss in both
      preclinical and clinical studies. The rapid degradation of both GIP and GLP-1 by
      the enzyme dipeptidyl peptidase-4 has led to the development of degradation
      resistant GLP-1-receptor agonists and dipeptidyl peptidase-4 inhibitors for the
      treatment of type 2 diabetes. These agents decrease hemoglobin A1c (HbA1c) safely
      without weight gain in subjects with type 2 diabetes. GLP-1 and GIP integrate
      nutrient-derived signals to control food intake, energy absorption, and
      assimilation. Recently approved therapeutic agents based on potentiation of
      incretin action provide new physiologically based approaches for the treatment of
      type 2 diabetes.

PMID- 17498509
TI  - The role of CNS fuel sensing in energy and glucose regulation.
AB  - Individual cells must carefully regulate their energy flux to ensure nutrient
      levels are adequate to maintain normal cellular activity. The same principle
      holds in multicellular organisms. Thus, for mammals to perform necessary
      physiological functions, sufficient nutrients need to be available. It is more
      complex, however, to understand how the energy status of different cells impacts
      on the overall energy balance of the entire organism. We propose that the central
      nervous system is the critical organ for the coordination of intracellular
      metabolic processes that are essential to guarantee energy homeostasis at the
      organismal level. In particular, we suggest that in specific hypothalamic
      neurons, evolutionarily conserved fuel sensors, such as adenosine monophosphate
      activated protein kinase and mammalian target of rapamycin (mTOR), integrate
      sensory input from nutrients, including those derived from recently ingested food
      or those that are stored in adipose tissue, to regulate effector pathways
      responsible for fuel intake and utilization. The corollary to this hypothesis is
      that dysregulation of these fuel-sensing mechanisms in the brain may contribute
      to metabolic dysregulation underlying diseases, such as obesity and type 2
      diabetes.

PMID- 17498510
TI  - Obesity, inflammation, and insulin resistance.
AB  - Weight gain and obesity are major risk factors for conditions and diseases
      ranging from insulin resistance and type 2 diabetes mellitus to atherosclerosis
      and the sequelae of nonalcoholic fatty liver disease. A chronic, subacute state
      of inflammation often accompanies the accumulation of excess lipid in adipose
      tissue and liver (hepatic steatosis), evidenced by changes in both inflammatory
      cells and biochemical markers of inflammation. These changes can be seen in the
      involved tissues and systemically, in terms of elevated circulating levels of
      inflammatory markers. The link between obesity and inflammation has therefore
      raised the important question of whether obesity-induced inflammation plays a
      pathogenic role in the development and progression of these disorders. We review
      the rapidly expanding body of animal and clinical data that support potential
      roles for inflammation in the pathogenesis of insulin resistance and type 2
      diabetes mellitus.

PMID- 17498511
TI  - Obesity and atherogenic dyslipidemia.
AB  - Obesity is associated with an increased risk of coronary heart disease, in part
      due to its strong association with atherogenic dyslipidemia, characterized by
      high triglycerides and low high-density lipoprotein (HDL) cholesterol. There has
      been substantial research effort focused on the mechanisms of the link between
      obesity and atherogenic dyslipidemia, both in the absence and presence of insulin
      resistance. After a brief overview of the epidemiology of atherogenic
      dyslipidemia, this article details the known molecular mechanisms of adipocyte
      function and its relationship to apoB-containing lipoprotein assembly and
      metabolism, both in the healthy as well as in the obese states. We also discuss
      the pathophysiology of low HDL cholesterol in obesity and the implications for
      cardiovascular disease risk.

PMID- 17498512
TI  - Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic
      fatty liver disease.
AB  - Nonalcoholic fatty liver disease represents a spectrum of histopathologic
      abnormalities, the prevalence of which may be as high as 24% of the population of
      the United States. Nonalcoholic fatty liver disease will play a major role in the
      science and practice of gastroenterology in the near future. The fundamental
      derangement in nonalcoholic fatty liver disease is insulin resistance, a key
      component of the metabolic syndrome, which includes type 2 diabetes mellitus,
      hypertriglyceridemia, essential hypertension, low circulating high-density
      lipoprotein, and obesity. The natural history of fatty liver disease is not
      always benign, and causality for cirrhosis and chronic liver disease is well
      founded in the literature. Treatment strategies are limited and, at present, are
      primarily focused on weight loss and use of insulin sensitizing agents, including
      the thiazolidenediones. Recent data clearly implicate hepatic insulin resistance
      as a culprit in accumulation of free fatty acids as triglycerides in hepatocytes.
      Hepatic insulin resistance is clearly exacerbated by systemic insulin resistance
      and impaired handling by skeletal muscle and adipose tissue of both glucose and
      free fatty acids. The key consequence of hepatic insulin resistance, impaired
      hepatocyte insulin signal transduction, results in adverse cellular and molecular
      changes exacerbating hepatocyte triglyceride storage. Cytokines secreted by white
      adipose tissue, adipokines, have emerged as key players in glucose and fat
      metabolism previously thought controlled largely by insulin. Modulation of
      adipokines may aid in further understanding of the pathophysiology and treatment
      of nonalcoholic fatty liver disease.

PMID- 17498513
TI  - The role of obesity and related metabolic disturbances in cancers of the colon,
      prostate, and pancreas.
AB  - Recent evidence indicates that obesity and related metabolic abnormalities are
      associated with increased incidence or mortality for a number of cancers,
      including those of the colon, prostate, and pancreas. Obesity, physical
      inactivity, visceral adiposity, hyperglycemia, and hyperinsulinemia are
      relatively consistent risk factors for colon cancer and adenoma. Also, patients
      with type 2 diabetes mellitus have a higher risk of colon cancer. For prostate
      cancer, the relationship to obesity appears more complex. Obesity seems to
      contribute to a greater risk of aggressive or fatal prostate cancer but perhaps
      to a lower risk of nonaggressive prostate cancer. Furthermore, men with type 2
      diabetes mellitus are at lower risk of developing prostate cancer. Long-standing
      type 2 diabetes increases the risk of pancreatic cancer by approximately 50%.
      Furthermore, over the past 6 years, a large number of cohort studies have
      reported positive associations between obesity and pancreatic cancer. Together
      with data from prediagnostic blood specimens showing positive associations
      between glucose levels and pancreatic cancer up to 25 years later, sufficient
      evidence now supports a strong role for diabetes and obesity in pancreatic cancer
      etiology. The mechanisms for these associations, however, remain speculative and
      deserve further study. Hyperinsulinemia may be important, but the role of
      oxidative stress initiated by hyperglycemia also deserves further attention.

PMID- 17498514
TI  - Lifestyle modification for the management of obesity.
AB  - Several expert panels have recommended that obese individuals attempt to lose 10%
      of their initial body weight through a combination of diet, physical activity,
      and behavior therapy (frequently referred to as lifestyle modification). This
      article reviews the short-and long-term results of lifestyle modification and
      methods to improve them. Randomized controlled trials were examined that compared
      different diet and activity interventions for inducing and maintaining weight
      loss. Studies that compared different methods of providing lifestyle
      modification, including on-site vs. Internet-based delivery, also were examined.
      A comprehensive lifestyle modification program was found to induce a loss of
      approximately 10% of initial weight in 16 to 26 weeks of group or individual
      treatment, delivered on-site. Comprehensive Internet-based programs induced a
      loss of approximately half this size. Patients' consumption of portion-controlled
      diets, including liquid meal replacements, was associated with significantly
      greater short-term weight loss than was the consumption of isocaloric diets
      comprised of conventional foods. Factors associated with long-term weight control
      included continued patient-practitioner contact (whether on-site or by e-mail),
      high levels of physical activity, and the long-term use of pharmacotherapy
      combined with lifestyle modification. In summary, lifestyle modification induces
      clinically significant weight loss that is associated with the prevention or
      amelioration of cardiovascular risk factors.

PMID- 17498515
TI  - Drug treatment of the overweight patient.
AB  - Three medications with approval for long-term use in the treatment of obesity are
      currently available in the United States. Sibutramine (U.S. Food and Drug
      Administration [FDA] approved in 1997), orlistat (FDA approved in 1999), and
      rimonabant (available in Europe and given FDA approvable status in 2006 and
      expected to be marketed in 2007) represent modern approaches to medications used
      adjunctively for weight management. As demonstrated in large clinical trials of 2
      to 4 years' duration, these medications significantly increase weight loss
      compared with placebo; weight loss with these drugs reaches a nadir between 20
      and 28 weeks; weight loss, averaged 8%-10%, with the placebo contributing 4%-6%
      of that. Weight maintenance is demonstrated as long as adherence to medication
      continues. All medications have side effects that need to be considered. For
      sibutramine, there is a rise in blood pressure and heart rate that may require
      discontinuation of the drug in a small percent of patients. For orlistat,
      steatorrhea produces the principal gastrointestinal side effects. Rimonabant
      appears to have a favorable safety and tolerability profile. Nausea and
      gastrointestinal symptoms are the chief tolerability issue, but they are usually
      self-limited. In addition there are several drugs and drug combinations in phase
      2 or phase 2 trials that will be reported on in the coming years.

PMID- 17498516
TI  - Bariatric surgery: a review of procedures and outcomes.
AB  - The prevalence of obesity has increased in recent decades, and obesity is now one
      of the leading public health concerns on a worldwide scale. There is accumulating
      agreement that bariatric surgery is currently the most efficacious and enduring
      treatment for clinically severe obesity, and as a result, the number of bariatric
      surgery procedures performed has risen dramatically in recent years. This review
      will summarize historic and contemporary bariatric surgical techniques, including
      gastric bypass (open and laparoscopic), laparoscopic adjustable gastric banding,
      and biliopancreatic diversion (with or without duodenal switch). Data are
      presented on bariatric surgery outcomes, focusing on weight loss and obesity
      related comorbidities. We also review possible complications from surgery.
      Bariatric surgery patients undergo many dramatic lifestyle changes, and
      comprehensive presurgical screening conducted by a multidisciplinary team is
      important to prepare patients for the numerous changes necessary for successful
      outcome. In addition, comprehensive presurgical screening can aid the treatment
      team in identifying patients who would benefit from additional services prior to
      or following surgery. Further research focused on presurgical variables that
      predict outcome-especially the longer term outcome-of bariatric surgery is
      needed. At present, approximately 1% of eligible individuals with morbid obesity
      receive bariatric surgery. In addition, there appears to be inequity in access to
      weight loss surgery. Given the accumulating evidence that bariatric surgery is
      efficacious in producing significant and durable weight loss, improving obesity
      related comorbidities, and extending survival, the U.S. healthcare system should
      examine ways to improve access to this treatment for obesity.

PMID- 17498517
TI  - Report of the American Gastroenterological Association (AGA) Institute Obesity
      Task Force.

PMID- 17498518
TI  - Experimental Nipah virus infection in pteropid bats (Pteropus poliocephalus).
AB  - Seventeen grey-headed fruit bats (Pteropus poliocephalus) were inoculated
      subcutaneously with an isolate of Nipah virus derived from a fatally infected
      human. A control group of eight guinea-pigs was inoculated intraperitoneally with
      the same isolate in order to confirm virulence. Three of eight infected guinea
      pigs developed clinical signs 7-9 days post-inoculation. Infected fruit bats
      developed a subclinical infection characterized by the transient presence of
      virus within selected viscera, episodic viral excretion and seroconversion. A
      range of histopathological changes was observed within the tissues of infected
      bats. Nipah virus was excreted in bat urine while neutralizing antibody was
      present in serum. This intermittent, low-level excretion of Nipah virus in the
      urine of bats may be sufficient to sustain the net reproductive value of the
      virus in a species where there is regular urine contamination of the fur, mutual
      grooming, and where urine droplets are a feature of the environment.

PMID- 17498519
TI  - Advances in cell-based therapy for structural heart disease.
AB  - Congestive heart failure and coronary artery disease are the leading causes of
      morbidity and mortality in the United States despite substantial therapeutic
      advances in the last half century. Only very recently have studies arisen that
      support possibility of regenerating tissue of damaged human organs including the
      heart. In this regard, there is growing pre-clinical and clinical evidence
      demonstrating the safety and efficacy of cell-based myocardial regeneration using
      a variety of cell lines. Although the data on the exact mechanism of action and
      the fate of the administered cells is controversial, there is consistent evidence
      for improved cardiac function and myocardial regeneration using different cell
      types. This extraordinarily exciting scientific advance has forced cardiovascular
      scientists to re-evaluate the long-held paradigm of cardiac myocyte terminal
      differentiation and life-long longevity of the cardiac myocytes that comprise the
      heart. Whereas, these new ideas originated with attempts to perform cellular
      transplantation using exogenous stem or precursor cells, mechanistic insights
      have rapidly evolved to the realization that adult organs harbor stem cells with
      significant plasticity, capable of repopulating their respective organ. Indeed
      these cells may be harnessed as a therapeutic agent or may represent the target
      of regenerative therapeutic strategies.

PMID- 17498520
TI  - Stem cells and their potential in cell-based cardiac therapies.
AB  - Stem cells are potential agents for the treatment of myocardial infarcts among
      other heart diseases. Over the past decade, the scientific community has
      extensively used a wide variety of cells and examined their capacity to both
      regenerate the infarcted myocardium and improve functionally the diseased hearts.
      Some of the cells used include skeletal myoblasts, bone marrow-derived cells,
      adult cardiac resident stem cells, mesenchymal stem cells, and both mouse and
      human embryonic stem cells (Nat Biotechnol 2005;23:845-856). The reported
      cardiogenic capacity of the utilitized stem cells is assayed both in vitro
      through the use of differentiation paradigms and in vivo through transplantation
      into a variety of animal models of cardiac disease. The purpose of this review
      article is to summarize recent stem cell applications in cell-based cardiac
      therapies and their outcomes.

PMID- 17498521
TI  - In vivo tracking in cardiac stem cell-based therapy.
AB  - Cell-based therapy has been heralded as a promising, novel therapeutic strategy
      for cardiovascular diseases. Despite a rapid transition from animal studies to
      clinical trials, there remain numerous unresolved, and at times, controversial
      issues with respect to underlying molecular mechanisms. In parallel, recent
      advances in the field of molecular imaging has provided a means to bridge the gap
      in knowledge through in vivo stem cells tracking. Herein, we review current in
      vivo imaging techniques and future directions for tracking the effects of cell
      based therapy.

PMID- 17498523
TI  - Acute [corrected] stroke thrombolysis: an update [corrected].
AB  - Acute stroke therapy took a major step forward in 1996 after the approval of
      Intravenous (IV) tissue plasminogen activator (t-PA) by the US Food and Drug
      Administration for patients presenting within 3 hours of the onset of stroke
      symptoms. Since that time, there have been considerable advances in imaging
      techniques as well as the advent of devices to help in the management of acute
      stroke patients. As a result, the arsenal to treat acute stroke has grown, and
      the field of stroke as a subspecialty of neurology has emerged. Despite these
      advances, only 3% to 8% of eligible patients with acute stroke in the United
      States are administered thrombolytics.(1) We herein review the use of
      thrombolytics in stroke and provide an overview of the imaging advances, new
      devices, and recent trials that are shaping modern stroke therapy. Finally, we
      provide a practical approach to the management of acute stroke, specifically for
      the practicing cardiologist, who may encounter stroke during cardiac
      catheterization, post myocardial infarction (MI), and in a variety of other
      settings.

PMID- 17498522
TI  - Biologic properties of endothelial progenitor cells and their potential for cell
      therapy.
AB  - Recent studies indicate that portions of ischemic and tumor neovasculature are
      derived by neovasculogenesis, whereby bone marrow (BM)-derived circulating
      endothelial progenitor cells (EPCs) home to sites of regenerative or malignant
      growth and contribute to blood vessel formation. Recent data from animal models
      suggest that a variety of cell types, including unfractionated BM mononuclear
      cells and those obtained by ex vivo expansion of human peripheral blood or
      enriched progenitors, can function as EPCs to promote tissue vasculogenesis,
      regeneration, and repair when introduced in vivo. The promising preclinical
      results have led to several human clinical trials using BM as a potential source
      of EPCs in cardiac repair as well as ongoing basic research on using EPCs in
      tissue engineering or as cell therapy to target tumor growth.

PMID- 17498524
TI  - Carcinoid heart disease.
AB  - Carcinoid heart disease is a rare form of valvular heart disease. The management
      of these patients is complex, as the systemic malignant disease and the cardiac
      involvement have to be considered at the same time. Progress in the treatment of
      patients with carcinoid disease has resulted in improved symptom control and
      survival. Development and progression of carcinoid heart disease are associated
      with increased morbidity and mortality. In patients with severe cardiac
      involvement and well-controlled systemic disease, cardiac surgery has been
      recognized as the only effective treatment option. Valve replacement surgery may
      not only be beneficial in terms of symptom relief, but may also contribute to the
      improved survival observed over the past 2 decades in patients with carcinoid
      heart disease. Early diagnosis and early surgical treatment in appropriately
      selected patients may provide the best results. In this article, we review the
      current literature regarding the biology, diagnosis, treatment, and prognosis of
      carcinoid heart disease.

PMID- 17498528
TI  - Breast cancer risk assessment and risk reduction.
AB  - Until recently, the primary message of breast health awareness programs was that
      early detection is a woman's best protection against breast cancer, because there
      was no way to prevent it. Currently, however, tamoxifen is approved for
      chemoprevention of breast cancer in high-risk women, and studies are underway
      evaluating other medications that may decrease breast cancer risk. Data have also
      become available regarding the efficacy of surgical strategies to reduce breast
      cancer risk. Any prevention method, however, will have associated risk of
      complications or adverse effects, and determining the net risk/benefit ratio
      depends on the ability to accurately quantify a woman's baseline likelihood of
      developing breast cancer. This article reviews available methods for assessing
      and reducing breast cancer risk.

PMID- 17498527
TI  - Review of breast cancer clinical trials conducted by the National Surgical
      Adjuvant Breast Project.
AB  - The National Surgical Adjuvant Breast Project (NSABP) is a clinical trials
      cooperative group funded by the National Cancer Institute that has been
      responsible for the majority of prospective, randomized studies that have defined
      standards of breast cancer care in the United States during the past 4 decades.
      This article summarizes the design of and findings from a selection of their
      landmark studies. Results from their many successfully completed trials have been
      reported as subset analyses, pooled analyses, and retrospective studies. This
      article focuses on presenting the study designs, aims, and primary endpoint
      results of these studies.

PMID- 17498529
TI  - Prophylactic mastectomy.
AB  - With availability of genetic testing and development of statistical models for
      risk stratification, more women are being identified as having increased risk for
      breast cancer. A number of risk-reducing treatment options with varying efficacy
      exist for them, including frequent surveillance, chemoprevention, prophylactic
      salpingo-oophorectomy (PSO), and prophylactic mastectomy (PM). Those most likely
      to benefit from PM are BRCA gene carriers and those who have a strong family
      history of breast cancer. Prevetive PM remains controversial, however. There are
      no randomized controlled trials to substantiate the potential benefit or harms of
      PM. This article describes the high-risk women in whom PM may be considered, and
      summarizes data on the efficacy of PM as a treatment for the prevention of breast
      cancer.

PMID- 17498530
TI  - Ductal carcinoma in situ--current management.
AB  - This article summarizes the modern evidence-based management of ductal carcinoma
      in situ. The data addressing the surgical issues, including indications for
      mastectomy and the use of sentinel node biopsy, are presented. The randomized
      trials examining the role of radiation therapy after breast-conserving surgery
      and the use of tamoxifen in ductal carcinoma in situ are discussed. Factors to
      consider in developing a management strategy for the individual patient are
      elucidated in the final section.

PMID- 17498531
TI  - Lymphatic mapping techniques and sentinel lymph node biopsy in breast cancer.
AB  - The axillary nodal status is accepted universally as the most powerful prognostic
      tool available for early stage breast cancer. The removal of level I and level II
      lymph nodes at axillary node dissection (ALND) is the most accurate method to
      assess nodal status, and it is the universal standard; however, it is associated
      with several adverse long-term sequelae. Lymphatic mapping with sentinel lymph
      node biopsy has emerged as an effective and safe alternative to the ALND for
      detecting axillary metastases. This article discusses some lymphatic mapping
      methodology.

PMID- 17498532
TI  - Axillary management after sentinel lymph node biopsy in breast cancer patients.
AB  - According to the available data, sentinel lymph node (SLN) biopsy is proving to
      be an accurate staging technique with less post-surgical morbidity than standard
      axillary lymph node dissection (ALND). Survival benefits associated with SLN
      biopsy and, as well as the significance of IHC detected micrometastases have yet
      to be determined. The long term results of several multicenter trials are
      pending, yet preliminary results are in favor of abandoning ALND in favor of the
      less invasive alternative. Despite this, ALND remains the standard of care in
      breast cancer patients with clinically palpable axillary lymph nodes that are
      suspicious for metastatic disease. Although controversial, many clinicians
      believe that axillary metastases will precede systemic spread of disease.
      Therefore, axillary clearance of clinically palpable nodes could potentially
      quell the progression of metastases. Regardless of whether or not this theory is
      true, not many would argue against debulking suspicious nodal disease.

PMID- 17498533
TI  - Management of patients with locally advanced breast cancer.
AB  - The indications and benefits of postmastectomy radiation therapy (PMRT) continue
      to evolve. Advances in systemic adjuvant therapy and targeted therapy for breast
      cancer are likely to play an increasingly important role in control of
      locoregional as well as distant disease. Ongoing scrutiny of patterns of chest
      wall failure will be required to define the net benefit derived from PMRT. This
      article discusses the 2001 American Society of Clinical Oncology guidelines for
      PMRT and current practices using PMRT in selected groups of patients who have
      breast cancer.

PMID- 17498534
TI  - Neoadjuvant systemic therapy and the surgical management of breast cancer.
AB  - Neoadjuvant chemotherapy is standard management for women who have locally
      advanced or inflammatory breast cancer, but can be applied to all women who may
      require postoperative chemotherapy for early-stage breast cancer. Disease-free
      survival and overall survival are equivalent between patients treated with
      neoadjuvant chemotherapy and patients treated with the same regimen
      postoperatively. Preoperative chemotherapy can offer women less morbid surgical
      treatment by down-staging both the primary breast tumor and axillary metastases.
      Finally, response to chemotherapy can inform clinicians of the chemosensitivity
      of the tumor, and can predict long-term outcome for women who have breast cancer.

PMID- 17498535
TI  - Pregnancy-associated breast cancer: a literature review.
AB  - Breast cancer is one of the most commonly diagnosed cancers of pregnancy. The
      diagnostic and therapeutic implications in this population are special. These
      women typically present with more advanced disease that carries a poorer
      prognosis. This article highlights patient care in this population, where
      aggressive care must be modified to ensure fetal protection.

PMID- 17498536
TI  - Complications in breast surgery.
AB  - Most breast operations are categorized as low-morbidity procedures, but a variety
      of complications can occur in association with diagnostic and multidisciplinary
      management procedures. Some of these complications are related to the breast
      itself, and others are associated with axillary staging procedures. This article
      first addresses some general, nonspecific complications (wound infections, seroma
      formation, hematoma). It then discusses complications that are specific to
      particular breast-related procedures: lumpectomy (including both diagnostic open
      biopsy and breast-conservation therapy for cancer), mastectomy; axillary lymph
      node dissection, lymphatic mapping/sentinel lymph node biopsy, and
      reconstruction.

PMID- 17498537
TI  - Breast reconstruction.
AB  - During the last century, breast reconstruction after mastectomy has become an
      important part of comprehensive treatment for patients who have breast cancer.
      Breast reconstruction initially was created to reduce complications of mastectomy
      and to diminish chest wall deformities. Now, however, it is known that
      reconstruction also can improve the psychosocial well-being and quality of life
      of patients who have breast cancer. This article reviews the techniques used for
      breast construction after breast surgery.

PMID- 17498538
TI  - Use of ultrasound in breast surgery.
AB  - The use of ultrasound has grown tremendously since it was introduced in 1951.
      This article describes use of this modality in patients who have breast disease.

PMID- 17498539
TI  - Integrating partial breast irradiation into surgical practice and clinical
      trials.
AB  - The use of accelerated partial breast irradiation (APBI) in place of whole-breast
      irradiation (WBI) for breast-conservation therapy (BCT) is an area of intensive
      clinical investigation. This article describes evolving methods of APBI in
      comparison to WBI and in the setting of ongoing clinical trials.

PMID- 17498540
TI  - Overview of adjuvant systemic therapy in early stage breast cancer.
AB  - The benefits of adjuvant systemic therapy in reducing risk of distant relapse
      from breast cancer have been recognized for several decades. The intent of
      adjuvant therapy is to eliminate the occult micrometastatic breast cancer burden
      before it progresses into clinically apparent disease. Successful delivery of
      effective adjuvant systemic therapy as a complement to surgical management of
      breast cancer has contributed to the steady declines in breast cancer mortality
      observed internationally over the past 2 decades. Ongoing clinical and
      translational research in breast cancer seeks to improve the efficacy of systemic
      agents for use in the conventional postoperative (adjuvant) setting.

PMID- 17498541
TI  - Postmastectomy radiation therapy: indications and controversies.
AB  - The indications and benefits of postmastectomy radiation therapy (PMRT) continue
      to evolve. Advances in systemic adjuvant therapy and targeted therapy for breast
      cancer are likely to play an increasingly important role in control of
      locoregional as well as distant disease. Ongoing scrutiny of patterns of chest
      wall failure will be required to define the net benefit derived from PMRT. This
      article discusses the 2001 American Society of Clinical Oncology guidelines for
      PMRT and current practices using PMRT in selected groups of patients who have
      breast cancer.

PMID- 17498542
TI  - Locoregional Resection in Stage IV breast cancer: tumor biology, molecular and
      clinical perspectives.
AB  - The intact primary in patients diagnosed with Stage IV breast cancer is generally
      reserved for palliative indications. Haagensen and Stout's 1943 criteria of
      inoperability for carcinoma of the breast, including tumor fixation to the chest
      wall, ulceration, and peau d'orange, hold true. Surgery alone is unlikely to
      prolong life in such patients. Improvements in breast cancer screening and
      awareness mean fewer patients having inoperable breast cancer. The current
      problem is that imagining studies reveal some patients to have oligometastatic
      disease with an intact primary. This article considers surgical treatment as part
      of multimodal Stage IV breast cancer treatment for such patients. Several
      challenges to previous dogma to never operate on Stage IV breast cancer patients
      except with palliative intent have arisen.

PMID- 17498543
TI  - Radiofrequency, cryoablation, and other modalities for breast cancer ablation.
AB  - This article describes several methods for breast cancer ablation. It focuses
      especially on radiofrequency ablation, describing how it works, relate findings
      from recent studies, and comparing it with other methods of breast cancer
      ablation.

PMID- 17498544
TI  - Investigating the phenotypes and genotypes of breast cancer in women with African
      ancestry: the need for more genetic epidemiology.
AB  - Disparities in incidence, mortality, and age of onset of breast cancer between
      women of African ancestry and women of other racial/ethnic backgrounds are poorly
      understood. A more comprehensive elaboration of genetic variants that occur in
      African women may facilitate a better understanding of the disease in African
      American women and explain the role of genetic admixture on the variation in the
      expression of the disease. Large-scale, population-based databases that document
      the cancer burden of Africa are lacking because of financial and infrastructural
      limitations. The development of such programs would represent an important cancer
      control and research strategy.

PMID- 17498545
TI  - The development of synovial joints.
AB  - During vertebrate evolution, successful adaptation of animal limbs to a variety
      of ecological niches depended largely on the formation and positioning of
      synovial joints. The function of a joint is to allow smooth articulation between
      opposing skeletal elements and to transmit biomechanical loads through the
      structure, and this is achieved through covering the ends of bones with articular
      cartilage, lubricating the joint with synovial fluid, using ligaments to bind the
      skeletal elements together, and encapsulating the joint in a protective fibrous
      layer of tissue. The diversity of limb generation has been proposed to occur
      through sequential branching and segmentation of precartilaginous skeletal
      elements along the proximodistal axis of the limb. The position of future joints
      is first delimited by areas of higher cell density called interzones initially
      through an as yet unidentified inductive signal, subsequently specification of
      these regions is controlled hierarchically by wnt14 and gdf5, respectively. Joint
      forming cell fate although specified is not fixed, and joints will fuse if growth
      factor signaling is perturbed. Cavitation, the separation of the two opposing
      skeletal elements, and joint morphogenesis, the process whereby the joint cells
      organize and mature to establish a functional interlocking and reciprocally
      shaped joint, are slowly being unraveled through studying the plethora of
      molecules that make up the unique extracellular matrix of the forming structure.
      The joint lining tissue, articular cartilage, is avascular, and this limits its
      reparative capacity such that arthritis and associated joint pathologies are the
      single largest cause of disability in the adult population. Recent discoveries of
      adult stem cells and more specifically the isolation of chondroprogenitor cells
      from articular cartilage are extending available therapeutic options, though only
      with a more complete understanding of synovial joint development can such options
      have greater chances of success.

PMID- 17498546
TI  - Development of a sexually differentiated behavior and its underlying CNS arousal
      functions.
AB  - This chapter addresses questions regarding lordosis behavior, the most extremely
      sexually differentiated behavior that has been analyzed for its neural and
      molecular mechanisms. Analysis of this behavior has proved for the first time
      that specific biochemical reactions in specific nerve cell groups in the brain
      determine a mammalian behavior. Lordosis is done by the female but not by the
      male. How did the process of sexual differentiation occur? A large literature
      implicates high levels of testosterone during a critical period during
      development as being responsible for the defeminization of the brain. A new idea,
      however, offers the possibility of direct genetic influences independent of
      testosterone levels themselves. We propose here that Mullerian Inhibiting
      Substance (MIS) and its receptors could constitute an example of a nonandrogenic
      genetic influence. Further, specific sexual behaviors depend on underlying
      arousal states in the central nervous system (CNS). We have proposed the concept
      of generalized CNS arousal and provide information as to how generalized arousal
      forces interact with specifically sexual influences, thus to facilitate sexually
      differentiated mating behaviors.

PMID- 17498547
TI  - Phosphodiesterases regulate airway smooth muscle function in health and disease.
AB  - On the basis of structure, regulation, and kinetic properties, phosphodiesterases
      (PDEs) represent a superfamily of enzymes divided into 11 subfamilies that
      catalyze cytosolic levels of 3',5'-cyclic adenosine monophosphate (cAMP) or 3',5'
      cyclic guanosine monophosphate (cGMP) to 5'-AMP or 5'-GMP, respectively. PDE4
      represents the major PDE expressed in inflammatory cells as well as airway smooth
      muscle (ASM), and selective PDE4 inhibitors provide a broad spectrum of anti
      inflammatory effects such as abrogating cytokine and chemokine release from
      inflammatory cells and inhibiting inflammatory cell trafficking. Due to cell- and
      tissue-specific gene expression and regulation, PDEs modulate unique organ-based
      functions. New tools or compounds that selectively inhibit PDE subfamilies and
      genetically engineered mice deficient in selective isoforms have greatly enhanced
      our understanding of PDE function in airway inflammation and resident cell
      function. This chapter will focus on recent advances in our understanding of the
      role of PDE in regulating ASM function.

PMID- 17498548
TI  - Role of astrocytes in matching blood flow to neuronal activity.
AB  - The brain is critically dependent on oxygen and glucose supply for normal
      function. Various neurovascular control mechanisms assure that the blood supply
      of the brain is adequate to meet the energy needs of its components. Emerging
      evidence shows that neuronal activity can control microcirculation using
      astrocytes as a mediator. Astrocytes can sense neuronal activity and are involved
      in signal transmission. Synaptic activity triggers an increase in the
      intracellular calcium concentration [Ca(2+)]i of adjacent astrocytes, stimulating
      the release of adenosine triphosphate (ATP) and glutamate. The released ATP
      mediates the propagation of Ca(2+) waves between neighboring astrocytes, thereby
      recruiting them to mediate adequate cerebrovascular response to neuronal
      activation. Simultaneously, sodium-dependent glutamate uptake in astrocytes
      generates Na(+) waves and subsequently increases glucose uptake and metabolism
      that leads to the formation of lactate, which is then delivered to neurons as an
      energy substrate. Further, astrocytic Ca(2+) elevations can lead to secretion of
      vasodilatory substances from perivascular endfeet, such as epoxyeicosatrienoic
      acid (EETs), adenosine, nitric oxide (NO), and cyclooxygenase-2 (COX-2)
      metabolites, resulting in increased local blood flow. Thus, astrocytes by
      releasing vasoactive molecules mediate the neuron-astrocyte-endothelial signaling
      pathway and play a profound role in coupling blood flow to neuronal activity.

PMID- 17498549
TI  - Elastin-elastases and inflamm-aging.
AB  - Degradation of elastin, the main amorphous component of elastic fibers, by
      elastases belonging to the serine, metallo, or cysteine families leads to the
      generation of elastin fragments, designated as elastokines in keeping with their
      cytokine-like properties. Generation of elastokines from one of the longest lived
      protein in human might represent a strong tissue repair signal. Indeed, they (1)
      exhibit potent chemotactic activity for leukocytes, (2) stimulate fibroblast and
      smooth muscle cell proliferation, and (3) display proangiogenic activity as
      potent as VEGF. However, continuous exposure of cells to these matrikines,
      through increased elastase(s) expression with age, can contribute to the
      formation of a chronic inflammatory state, that is, inflamm-aging. Importantly,
      binding of elastokines to S-Gal, their cognate receptor, proved to stimulate
      matrix metalloproteinase expression in normal and cancer cells. Besides, these
      elastin fragments can polarize lymphocytes toward a Th-1 response or induce an
      osteogenic response in smooth muscle cells, and arterial wall calcification. In
      this chapter, emphasis will be made on the contribution of elastokines on the
      genesis of age-related arterial wall diseases, particularly abdominal aortic
      aneurysms (AAAs). An elastokine theory of AAAs progression will be proposed. Age
      is one main risk factor of cancer incidence and development. The myriad of
      biological effects exerted by elastokines on stromal and inflammatory cells led
      us to hypothesize that they might be main actors in elaborating a favorable
      cancerization field in melanoma; for instance these peptides could catalyze the
      vertical growth phase transition in melanoma through increased expression of
      gelatinase A and membrane-type 1 matrix metalloproteinase.

PMID- 17498550
TI  - A phylogenetic approach to mapping cell fate.
AB  - Recent, surprising, and controversial discoveries have challenged conventional
      concepts regarding the origins and plasticity of stem cells, and their
      contributions to tissue regeneration, and highlight just how little is known
      about mammalian development in comparison to simpler model organisms. In the case
      of the transparent worm, Caenorhabditis elegans, Sulston and colleagues used a
      microscope to record the birth and death of every cell during its life, and the
      compilation of this "fate map" represents a milestone achievement of
      developmental biology. Determining a fate map for mammals or other higher
      organisms is more complicated because they are opaque, take a long time to
      mature, and have a tremendous number of cells. Consequently, fate mapping
      experiments have relied on tagging a progenitor cell with a dye or genetic marker
      in order to later identify its descendants. This approach, however, extracts
      little information because it demonstrates that a population of cells, all having
      inherited the same label, shares a common ancestor, but it does not reveal how
      cells in that population are related to one another. To avoid that problem, as
      well as technical limitations of current methods for mapping cell fate, we, and
      others, have developed a new strategy for retrospectively deriving cell fate maps
      by using phylogenetics to infer the order in which somatic mutations have arisen
      in the genomes of individual cells during development in multicellular organisms.
      DNA replication inevitably introduces mutations, particularly at repetitive
      sequences, every time a cell divides. It is thus possible to deduce the history
      of cell divisions by cataloging somatic mutations and phylogenetically
      reconstructing cell lineage. This approach has the potential to produce a
      complete mammalian cell fate map that, in principle, could describe the
      developmental lineage of any cell and help resolve outstanding questions of stem
      cell biology, tissue repair and maintenance, and aging.

PMID- 17498551
TI  - Cytogenetic alterations in renal tumors: a study of 38 Southeast Asian patients.
AB  - Renal cell carcinoma (RCC) is the most common cancer of the kidney. Cytogenetic
      studies of renal cell carcinoma have provided valuable insight into the
      chromosomal abnormalities involved in the genesis and progression of the disease,
      and have also helped in the classification of these tumors. Our objectives were
      to identify nonrandom chromosome abnormalities in renal tumors in a Southeast
      Asian population and also to determine if they differ from those in Western
      populations. Structural rearrangements of 3p were specific for clear cell RCC,
      with the most consistent structural rearrangement being a translocation between
      3p13 and 5q22. Gains of chromosomes 7 and 17 were observed in three and two cases
      of papillary RCC, respectively. All male patients with papillary RCC were noted
      to have loss of the Y chromosome. Gains of chromosomes 3 and 7, and structural
      aberration of chromosome 3, were observed in patients with transitional cell
      carcinoma of the renal pelvis (TCC). Chromosomal abnormalities in clear cell RCC,
      papillary RCC, and TCC did not differ between the Southeast Asian and Western
      populations. The aberrations seem to be common sporadic events, both
      geographically and racially.

PMID- 17498552
TI  - Automated Duet spot counting system and manual technologist scoring using dual
      fusion fluorescence in situ hybridization (D-FISH) strategy: comparison and
      application to FISH minimal residual disease testing in patients with chronic
      myeloid leukemia.
AB  - The automated BioView Duet system was compared with manual technologist scoring
      (MTS) using a BCR/ABL dual-fusion FISH (D-FISH) probe strategy for chronic
      myeloid leukemia (CML) specimens. In the first study, 500 nuclei were evaluated
      for 10 distinct signal patterns in various abnormal cell percentages from each of
      89 specimens. The Duet system correctly identified all 27 normal specimens and
      the abnormal signal pattern of all 63 abnormal specimens. The percentage of
      abnormal nuclei detected was also concordant, with an average difference between
      MTS and the Duet system of only 2.7%. However, achievement of accurate
      quantitative results required reclassification by a technologist for nearly 50%
      of nuclei per specimen. Next, the Duet system was used to evaluate BCR/ABL D-FISH
      for FISH minimal residual disease (MRD) detection in CML patients. Up to 6,000
      nuclei were evaluated for four signal pattern categories for each of 60 CML MRD
      samples. Excluding four abnormal specimens with insufficient samples, the Duet
      system correctly identified all of the abnormal specimens and identified four
      additional abnormal specimens previously diagnosed as normal by MTS. The
      technologist time required for evaluation and reclassification of the Duet system
      data for the FISH MRD samples averaged only 1 minute per case, saving significant
      technologist effort. We conclude that the Duet system appears to be more
      sensitive and cost-effective than MTS for CML FISH MRD testing.

PMID- 17498553
TI  - Detection of CCND1 amplification using laser capture microdissection coupled with
      real-time polymerase chain reaction in human esophageal squamous cell carcinoma.
AB  - Several methods have been used to detect CCND1 amplification or overexpression in
      esophageal squamous cell carcinoma (ESCC), but problems remain, associated with
      heterogeneity of tumor tissue and quantification of gene copies. Laser capture
      microdissection coupled with real-time polymerase chain reaction (PCR) is a
      reliable method for the molecular analysis of gene profiles in specific tissues.
      All 35 specimens of ESCC studied were paraffin-embedded, cut into tissue slides,
      and stained by hematoxylin-eosin. The pure ESCC cell and normal squamous
      epithelia populations were separated by LCM and then genomic DNA was extracted
      from the dissected cells. CCND1 amplification was detected with real-time FQ-PCR
      and with PCR. Amplification was calculated by the formula X = 2(-DeltaDeltaCt)
      and R = (CCND1/ACTB) CANCER/(CCND1/ACTB) NORMAL. Twenty (57%) of primary ESCC
      cancer cell groups had a detectable CCND1 amplification (range, 2.06-fold to 25.9
      fold) with real-time FQ-PCR, but only 2 of 15 primary ESCC cancer cell groups had
      detectable CCND1 amplification by PCR. CCND1 amplification was not correlated
      with age, sex, size of tumor, histological grade, and lymph node metastasis. In
      conclusion, LCM coupled with real-time fluorescence quantitative-PCR technique is
      more precise than PCR for the identifying amplified oncogenes; The role of CCND1
      amplification in ESCC development and progression needs more extensive study.

PMID- 17498554
TI  - Cytogenetic and molecular genetic analyses of giant cell glioblastoma multiforme
      reveal distinct profiles in giant cell and non-giant cell subpopulations.
AB  - We have comparatively analyzed mechanisms associated with chromosomal and
      microsatellite instability in giant cell glioblastoma multiforme (gcGBM) and
      classic GBM. This included microsatellite instability (MSI), loss of expression
      of four major mismatch repair (MMR) proteins, aberrations of five chromosomes,
      EGFR copy number, and TP53 mutations. MSI was more frequent among gcGBM (30 vs.
      7.8%, P = 0.054). TP53 mutations were more commonly observed in gcGBM (83.3%),
      whereas EGFR was amplified in just one gcGBM (8.3%). By tumor cell phenotype
      specific cytogenetic analysis of gcGBM, increased chromosome copy numbers were
      identified in 72-84% of giant cells but in only 4-14% of nongiant cells; in
      classic GBM, intermediate frequencies were noted (11-49%). Chromosome 10
      deletions were found in nongiant cells of all gcGBM cases but in only
      approximately 45% of the cell population in classic GBM. The present study shows
      a distinct pattern of cytogenetic alterations in nongiant and giant cell
      phenotypes in gcGBM and suggests that multinuclear giant cells evolve from
      nongiant tumor cells at an early tumor stage. Furthermore, the data point to
      differences in the profile of chromosomal and microsatellite instability in gcGBM
      and classic GBM that might underscore the distinct pathological features of both
      tumor subtypes.

PMID- 17498555
TI  - Comparative genomic hybridization analysis of abnormalities in chromosome 21 in
      childhood osteosarcoma.
AB  - Osteosarcomas (OS) are aggressive tumors of the bone and often have a poor
      prognosis. The tumors exhibit karyotypes with a high degree of complexity, which
      has made it difficult to determine whether any recurrent chromosomal aberrations
      characterize OS. To address inherent difficulties associated with classical
      cytogenetic analysis, comparative genomic hybridization (CGH) was applied to OS
      tissue. Forty-one pediatric OS specimens were analyzed by a CGH technique: 24
      female and 17 male patients, with a median age of 12 years and 4 months.
      Chromosomal abnormalities were highly diverse and variable, including gains of
      chromosome 1p, 2p, 3q, 5q, 5p, and 6p and losses of 14q (50% in 14q11.2), 15q,
      and 16p. A high level of losses of chromosome 21 was present (26/41 cases; P =
      0.008), most often loss of the 21q11.2 approximately 21 region. These novel
      findings in chromosome 21 of pediatric OS tumors suggest that specific sequences
      mapping to these chromosomal regions are likely to play a role in the development
      of OS.

PMID- 17498556
TI  - TAP1 gene polymorphisms and nasopharyngeal carcinoma risk in a Tunisian
      population.
AB  - To find out whether polymorphisms 333-Ile/Val and 637-Asp/Gly of the transporter
      part of the antigen processing 1 gene (TAP1) are associated with the development
      of nasopharyngeal carcinoma (NPC), we studied a total of 374 subjects (209
      patients and 165 controls). We used the amplification refractory mutation system
      polymerase chain reaction (ARMS-PCR) method for analyzing the TAP1 gene
      polymorphisms. We found a significant difference between the patients and the
      controls in both the TAP1 codon 333 and codon 637 (P = 0.009 and P = 0.002,
      respectively). We also found that genotypes with the A allele were present in 206
      patients with NPC and 155 controls (98.5 vs. 93.9%; P = 0.032; OR = 4.43) and
      that genotypes with the B allele were more often present in the control group (45
      vs. 32%; P = 0.004; OR = 0.48), suggesting a significant positive association of
      the A allele with NPC risk and a protective role of the B allele. We have
      observed an association between the distribution of TAP1 alleles and the NPC
      patient's age at onset, compared with controls. These results back up the fact
      that the etiology of NPC in intermediate-risk countries is completely different
      in each peak of age prevalence and that each peak may possess its own particular
      oncogenic mechanism.

PMID- 17498557
TI  - A haplotype encompassing the variant allele of DNA repair gene polymorphism
      ERCC2/XPD Lys751Gln but not the variant allele of Asp312Asn is associated with
      risk of lung cancer in a northeastern Chinese population.
AB  - The effect of the polymorphism of the DNA repair gene ERCC2/XPD Asp312Asn on the
      risk of lung cancer was investigated in a northeastern Chinese population. A
      hospital-based case-control study consisted of 201 lung cancer cases and 171
      cancer-free controls matched to age, sex, and ethnicity. A polymerase chain
      reaction-restriction fragment length polymorphism method was used for genotyping.
      Frequency of the variant C-allele of ERCC2 Asp312Asn was 0.006 among the controls
      in present study, which differs markedly from previous reports both in European
      ancestry populations and in other Chinese populations (all P < 0.001). The
      polymorphism was not associated with risk of lung cancer. Haplotype analysis
      including three previously studied polymorphisms (ERCC1 Asn118Asn, ERCC2
      Arg156Arg, and ERCC2 Lys751Gln) revealed that a haplotype consisting of
      ERCC1Asn118Asn(G)-ERCC2 Arg156Arg(C)-ERCC2 Asp312Asn(G)-ERCC2 Lys751Gln(C) was
      marginally associated with an increased risk of lung cancer (OR = 3.61, 95% CI =
      1.00-13.06, P = 0.04). Our data suggest that the polymorphism ERCC2 Lys751Gln or
      a haplotype encompassing the variant allele is associated with risk of lung
      cancer in this population. Studies including larger sample sizes are needed to
      elucidate the effects of these polymorphisms on lung cancer risk in this
      northeastern Chinese population.

PMID- 17498558
TI  - A case of chronic myeloproliferative syndrome followed by precursor T-cell acute
      lymphoblastic leukemia.
AB  - Interlineage switch from myeloid to lymphatic malignancies is a rare phenomenon.
      Progression from a BCR-ABL negative chronic myeloproliferative disorder (CMPD) to
      acute lymphoblastic leukemia (ALL) has been reported in very few cases. We
      describe the case of a 62-year-old man who developed precursor T-cell (pre-T) ALL
      18 months after the diagnosis of an unclassifiable chronic myeloproliferative
      syndrome (CMPD, U), which had been treated with hydroxyurea (HU) over 12 months.
      The transformation from CMPD to pre-T-ALL was accompanied by clonal evolution
      from normal to a high hyperdiploid karyotype with an i(17q):
      52,XY,+X,+2,+13,+14,+15,i(17)(q10),+19. Diverse pathways should be considered in
      this transformation process: although therapeutic induction of ALL is extremely
      rare and no MLL/11q23 rearrangement was detected by chromosome banding analyses
      and interphase fluorescence in situ hybridization (FISH), T-lineage ALL might
      have been caused by HU therapy for the CMPD. Chance coincidence of both disorders
      seems improbable, given the short interval from the diagnosis of the CMPD to the
      development of the pre-T-ALL, but nonetheless must be considered. A third
      explanation might be provided by a spontaneous interlineage switch, which would
      give further support to the theory that the CMPDs are disorders of a pluripotent
      stem cell. Interlineage switch might result from an aberrant differentiation of
      the malignant clone or from selection within a mixed population.

PMID- 17498559
TI  - Detection of chromosomal abnormalities in chronic lymphocytic leukemia increased
      by interphase fluorescence in situ hybridization in tetradecanoylphorbol acetate
      stimulated peripheral blood cells.
AB  - Interphase fluorescent in situ hybridization on unstimulated peripheral blood
      mononuclear cells (I-FISH-PBMC) is used to detect chromosomal abnormalities such
      as 11q-, 13q-, 17p-, and trisomy 12 in chronic lymphocytic leukemia (CLL). A
      total of 56 samples from 49 patients with CLL were studied using commercially
      available probes for chromosome regions 11q22.3 (ATM), 13q14 (13S272), 17p13
      (p53) and 12 centromere (D12Z3). We compared the results obtained with I-FISH
      PBMC and those with I-FISH on TPA (tetradecanoylphorbol acetate; phorbol-12
      myristate-13-acetate) stimulated peripheral blood cells (I-FISH-TPA) used for
      conventional cytogenetics, to evaluate the usefulness of I-FISH-TPA. The
      proportion of abnormal nuclei obtained with the I-FISH-TPA was higher than that
      found with I-FISH-PBMC (P < 0.001). Consequently, 15 cases with a negative or
      borderline result with I-FISH-PBMC became positive with I-FISH-TPA for 11q- (n =
      2), 13q- (n = 9), and trisomy 12 (n = 4). In all but one of these, chromosomal
      abnormalities were confirmed by either metaphase FISH or conventional G-banding.
      Detection of cytogenetic aberrations thus increased from 51% with I-FISH-PBMC to
      78% with I-FISH-TPA. Notably, all 15 of the cases that reached the diagnostic
      thresholds for 11q-, 13q-, and trisomy 12 had a slight lymphocytosis. An absolute
      lymphocyte count <8.7 x 10(9)/L was found to be the critical threshold (P =
      0.037) below which I-FISH-TPA rather than I-FISH-PBMC should be performed. Not
      only could I-FISH-TPA detect a higher proportion of abnormal interphase nuclei,
      but it could also identify abnormal CLL cases that might be overlooked with use
      of I-FISH-PBMC, especially those with low absolute lymphocyte counts. I-FISH-TPA
      is thus a reliable technique for clinical diagnostics in CLL.

PMID- 17498560
TI  - The A4396G polymorphism in interferon regulatory factor 1 is frequently expressed
      in breast cancer cell lines.
AB  - Loss or mutation of known tumor suppressor genes accounts for a small proportion
      of all breast cancers. We have recently shown that interferon regulatory factor 1
      (IRF1) is a putative tumor suppressor gene in breast cancer. We now report that
      the A4396G single nucleotide polymorphism in the IRF1 gene is more frequent in
      human breast cancer cell lines than in the general population (P = 0.01).
      Furthermore, A4396G is more frequently expressed in African American (black) than
      in European ancestry (white) subjects (n = 70 subjects; P < or = 0.001), leading
      to a significant difference in genotype distribution between these populations (P
      = 0.002).

PMID- 17498561
TI  - Simultaneous translocations of FGFR3/MMSET and CCND1 into two different IGH
      alleles in multiple myeloma: lack of concurrent activation of both proto
      oncogenes.
AB  - The simultaneous occurrence of two different translocations affecting both
      alleles of the IGH gene has rarely been reported in multiple myeloma. In such a
      case, two different oncogenes might become transcriptionally deregulated. To
      investigate this hypothesis, we have characterized the plasma cell leukemia cell
      line SK-MM2 and a primary myeloma both carrying simultaneous IGH-FGFR3/MMSET and
      IGH-CCND1 fusions as shown by multicolor fluorescence in situ hybridization.
      Remarkably, quantitative real-time polymerase chain reaction demonstrated that
      only one of the oncogene loci was transcriptionally upregulated in both
      instances. Moreover, the upregulated oncogenes differed between both samples.
      Thus, biallelic IGH translocations might exert different pathogenetic effects in
      plasma cell disorders.

PMID- 17498562
TI  - KIT exon 11 deletion-inversions represent complex mutations in gastrointestinal
      stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. KIT expression and mutational KIT activation have
      been documented in a majority of GISTs. Most mutations have been found in KIT
      juxtamembrane domain encoded by exon 11. Recently, we have identified three,
      complex KIT exon 11 mutations previously unreported in GISTs. These mutations
      consisted of several nucleotide deletions accompanied by insertions of inverted
      complementary DNA strand sequences. All three mutations were found in the 5' part
      of KIT exon 11. At the protein level, these mutations lead to the same end
      result: in-frame loss and insertion of a number of amino acids and could be
      considered examples of deletion-insertion. Although proper description of these
      mutations at the genomic level is a complex task and requires an individual
      approach, the uniform name deletion-inversion is suggested for this type of
      mutation, based on the present study. The frequency of deletion-inversions among
      KIT exon 11 mutant GISTs was estimated to be <0.5%, based on evaluation of 700
      KIT exon 11 mutants. Molecular events leading to formation of deletion-inversions
      remain elusive and should be studied further.

PMID- 17498563
TI  - A common 93-kb duplicated DNA sequence at 1q21.2 in acute lymphoblastic leukemia
      and Burkitt lymphoma.
AB  - In three patients with acute lymphoblastic leukemia (ALL) and in another with
      Burkitt lymphoma (BL), conventional cytogenetics and fluorescence in situ
      hybridization (FISH), applied singly or in combination, showed 1q duplication in
      two cases of ALL with hyperdiploid karyotypes, 1q duplication resulting from an
      unbalanced translocation in a third case of ALL, and inv dup(1)(q) in a patient
      with BL. Centromeric or telomeric breakpoints and extension of the 1q duplicons
      varied in each case. FISH defined a minimal, common duplicated region of 93kb at
      band 1q21.2 corresponding to clone RP11-212K13. In this region three putative
      oncogenes or tumor suppressor genes have been mapped: SF3B4 (splicing factor 3b,
      subunit 4), OTUD7B (OTU domain containing 7B), and MTMR11 (myotubularin related
      protein 11). For the first time, a minimal common 1q21.2 duplicated sequence has
      been identified in lymphoid malignancies in a region where putative oncogenes or
      suppressor genes have been mapped. This finding elucidates the genomic background
      of ALL and BL with 1q duplication and provides the basis for molecular studies
      investigating which genes are involved in leukemogenesis or disease progression
      in these cases.

PMID- 17498564
TI  - Cryptic t(15;17) in a patient with AML M3 and a complex karyotype.

PMID- 17498565
TI  - A new interphase fluorescence in situ hybridization approach for genomic
      rearrangements involving MLH1 and MSH6 in hereditary nonpolyposis colorectal
      cancer-suspected mutation-negative patients.

PMID- 17498566
TI  - Restrictions of a statistical mind: clinical relevance versus p values or when
      less is more.

PMID- 17498567
TI  - Common strategy for adult and pediatric medulloblastoma: a multicenter series of
      253 adults.
AB  - PURPOSE: To assess prognostic factors for adults with medulloblastoma in a
      multicenter, retrospective study. METHODS AND MATERIALS: Data were collected by
      file review or mail inquiry for 253 adults treated between 1975 to 2004.
      Radiologists or surgeons assessed disease characteristics, such as volume and
      extension. Patients were classified as having either high- or standard-risk
      disease. Prognostic factors were analyzed. RESULTS: Median patient age was 29
      years. Median follow-up was 7 years. Radiotherapy was delivered in 246 patients
      and radiochemotherapy in 142. Seventy-four patients relapsed. Respective 5- and
      10-year overall survival rates were 72% and 55%. Univariate analysis showed that
      survival significantly correlated with metastasis, postsurgical performance
      status, brainstem involvement, involvement of the floor of the fourth ventricle
      (V4), and radiation dose to the spine and to the posterior cerebral fossa (PCF).
      By multivariate analysis, brainstem, V4 involvement, and dose to the PCF were
      negative prognostic factors. In the standard-risk subgroup there was no overall
      survival difference between patients treated with axial doses of >or=34 Gy and
      patients treated with craniospinal doses <34 Gy plus chemotherapy. CONCLUSION: We
      report the largest series of medulloblastoma in adults. Prognostic factors were
      similar to those observed in children. Results suggest that patients with
      standard-risk disease could be treated with radiochemotherapy, reducing doses to
      the craniospinal area, maintaining at least 50 Gy to the PCF. The role of
      chemotherapy for this group is still unclear. A randomized study should be
      performed to confirm these results, but because frequency is very low, such a
      study would be difficult.

PMID- 17498568
TI  - Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal
      cancer: Phase I trial results.
AB  - PURPOSE: The overexpression of vascular endothelial growth factor (VEGF) is
      associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF
      inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor
      cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial
      was undertaken to evaluate the combination of bevacizumab, capecitabine,
      oxaliplatin, and radiation therapy in patients with rectal cancer. METHODS AND
      MATERIALS: Patients with pathologically confirmed adenocarcinoma of the rectum
      were eligible. Pretreatment staging included computerized tomography, endoscopic
      ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam
      radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin,
      and bevacizumab were administered concurrently with radiation therapy. After EBRT
      completion, patients were restaged and evaluated for surgery. Primary endpoints
      included the determination of dose-limiting toxicity and a recommended Phase II
      dose, non dose-limiting toxicity, and preliminary radiographic and pathologic
      response rates. RESULTS: Eleven patients were enrolled. All were evaluable for
      toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity
      (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The
      recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg
      Days 8 and 22, oxaliplatin 50 mg/m2 weekly, and capecitabine 625 mg/m2 bid during
      radiation days. Six patients had clinical responses. Two patients had a
      pathologic complete response, and 3 had microscopic disease only. One patient
      experienced a postoperative abscess, one a syncopal episode during adjuvant
      chemotherapy, and one a subclinical myocardial infarction during adjuvant
      chemotherapy. CONCLUSIONS: The combination of bevacizumab, capecitabine,
      oxaliplatin, and radiation therapy in rectal cancer was tolerable, with
      encouraging response rates. Further investigation with this regimen is being
      pursued in a Phase II setting.

PMID- 17498569
TI  - Short-term displacement and reproducibility of the breast and nodal targets under
      active breathing control.
AB  - PURPOSE: The short-term displacement and reproducibility of the breast or chest
      wall, and the internal mammary (IM), infraclavicular (ICV), and supraclavicular
      (SCV) nodal regions have been assessed as a function of breath-hold state using
      an active breathing control (ABC) device for patients receiving loco-regional
      breast radiation therapy. METHODS AND MATERIALS: Ten patients underwent computed
      tomographic scanning using an ABC device at breath-hold states of end-exhale and
      20%, 40%, 60%, and 80% of vital capacity (VC). Patients underwent scanning before
      treatment and at one third and two thirds of the way through treatment. A
      regional registration was performed for each target using a rigid-body
      transformation with mutual information as a metric. RESULTS: Between exhale and
      40% of VC, the mean displacement was 0.27/0.34, 0.24/0.31, 0.22/0.19, and
      0.13/0.19 cm anterior/superior for the breast or chest wall, and IM, ICV, and SCV
      nodes, respectively. At 80% of VC, the mean displacement from exhale was
      0.84/.88, 0.76/.79, 0.70/0.79, and 0.54/0.56 cm anterior/superior for the breast
      or chest wall, and IM, ICV, and SCV nodes, respectively. The short-term
      reproducibility (standard deviation) was <0.3 and <or=0.4 cm for 40% and 80% of
      VC, respectively. Displacements up to 1.9 cm were observed for individual
      patients. CONCLUSIONS: The short-term reproducibility of target position is
      <or=0.4 cm using ABC for all structures for all breath-hold states. This
      information can be used to guide treatment planning optimization studies that
      consider the effect of motion on target and normal tissue doses with and without
      active breathing control.

PMID- 17498570
TI  - Assessment of a model-based deformable image registration approach for radiation
      therapy planning.
AB  - PURPOSE: The aim of this study is to develop a surface-based deformable image
      registration strategy and to assess the accuracy of the system for the
      integration of multimodality imaging, image-guided radiation therapy, and
      assessment of geometrical change during and after therapy. METHODS AND MATERIALS:
      A surface-model-based deformable image registration system has been developed
      that enables quantitative description of geometrical change in multimodal images
      with high computational efficiency. Based on the deformation of organ surfaces, a
      volumetric deformation field is derived using different volumetric elasticity
      models as alternatives to finite-element modeling. RESULTS: The accuracy of the
      system was assessed both visually and quantitatively by tracking naturally
      occurring landmarks (bronchial bifurcations in the lung, vessel bifurcations in
      the liver, implanted gold markers in the prostate). The maximum displacements for
      lung, liver and prostate were 5.3 cm, 3.2 cm, and 0.6 cm respectively. The
      largest registration error (direction, mean +/- SD) for lung, liver and prostate
      were (inferior-superior, -0.21 +/- 0.38 cm), (anterior-posterior, -0.09 +/- 0.34
      cm), and (left-right, 0.04 +/- 0.38 cm) respectively, which was within the image
      resolution regardless of the deformation model. The computation time (2.7 GHz
      Intel Xeon) was on the order of seconds (e.g., 10 s for 2 prostate datasets), and
      deformed axial images could be viewed at interactive speed (less than 1 s for 512
      x 512 voxels). CONCLUSIONS: Surface-based deformable image registration enables
      the quantification of geometrical change in normal tissue and tumor with
      acceptable accuracy and speed.

PMID- 17498571
TI  - Automatic segmentation of pelvic structures from magnetic resonance images for
      prostate cancer radiotherapy.
AB  - PURPOSE: Target-volume and organ-at-risk delineation is a time-consuming task in
      radiotherapy planning. The development of automated segmentation tools remains
      problematic, because of pelvic organ shape variability. We evaluate a three
      dimensional (3D), deformable-model approach and a seeded region-growing algorithm
      for automatic delineation of the prostate and organs-at-risk on magnetic
      resonance images. METHODS AND MATERIALS: Manual and automatic delineation were
      compared in 24 patients using a sagittal T2-weighted (T2-w) turbo spin echo (TSE)
      sequence and an axial T1-weighted (T1-w) 3D fast-field echo (FFE) or TSE
      sequence. For automatic prostate delineation, an organ model-based method was
      used. Prostates without seminal vesicles were delineated as the clinical target
      volume (CTV). For automatic bladder and rectum delineation, a seeded region
      growing method was used. Manual contouring was considered the reference method.
      The following parameters were measured: volume ratio (Vr) (automatic/manual),
      volume overlap (Vo) (ratio of the volume of intersection to the volume of union;
      optimal value = 1), and correctly delineated volume (Vc) (percent ratio of the
      volume of intersection to the manually defined volume; optimal value = 100).
      RESULTS: For the CTV, the Vr, Vo, and Vc were 1.13 (+/-0.1 SD), 0.78 (+/-0.05
      SD), and 94.75 (+/-3.3 SD), respectively. For the rectum, the Vr, Vo, and Vc were
      0.97 (+/-0.1 SD), 0.78 (+/-0.06 SD), and 86.52 (+/-5 SD), respectively. For the
      bladder, the Vr, Vo, and Vc were 0.95 (+/-0.03 SD), 0.88 (+/-0.03 SD), and 91.29
      (+/-3.1 SD), respectively. CONCLUSIONS: Our results show that the organ-model
      method is robust, and results in reproducible prostate segmentation with minor
      interactive corrections. For automatic bladder and rectum delineation, magnetic
      resonance imaging soft-tissue contrast enables the use of region-growing methods.

PMID- 17498572
TI  - Successful treatment of a disseminated Sporothrix schenckii infection and in
      vitro analysis for antifungal susceptibility testing.
AB  - We report a case of a diabetic patient with localized osteoarticular
      sporotrichosis followed by widespread dissemination of the infection, which was
      successfully treated with amphotericin B. In addition, we evaluated the in vitro
      antifungal activity of 4 agents against both the mycelial and the yeast forms of
      the isolated fungus.

PMID- 17498573
TI  - Tissue Doppler imaging a new prognosticator for cardiovascular diseases.
AB  - Tissue Doppler imaging (TDI) is evolving as a useful echocardiographic tool for
      quantitative assessment of left ventricular (LV) systolic and diastolic function.
      Recent studies have explored the prognostic role of TDI-derived parameters in
      major cardiac diseases, such as heart failure, acute myocardial infarction, and
      hypertension. In these conditions, myocardial mitral annular or basal segmental
      (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to
      predict mortality or cardiovascular events. In particular, those with reduced Sm
      or Em values of <3 cm/s have a very poor prognosis. In heart failure and after
      myocardial infarction, noninvasive assessment of LV diastolic pressure by
      transmitral to mitral annular early diastolic velocity ratio (E/Ea or E/Em) is a
      strong prognosticator, especially when E/Ea is > or =15. In addition, systolic
      intraventricular dyssynchrony measured by segmental analysis of myocardial
      velocities is another independent predictor of adverse clinical outcome in heart
      failure subjects, even when the QRS duration is normal. In heart failure patients
      who received cardiac resynchronization therapy, the presence of systolic
      dyssynchrony at baseline is associated with favorable LV remodeling, which in
      turn predicts a favorable long-term clinical outcome. Finally, TDI and derived
      deformation parameters improve prognostic assessment during dobutamine stress
      echocardiography. A high mean Sm value in the basal segments of patients with
      suspected coronary artery disease is associated with lower mortality rate or
      myocardial infarction and is superior to the wall motion score.

PMID- 17498574
TI  - Screen testing cardiovascular prevention in asymptomatic diabetic patients.
AB  - It has recently been proposed that asymptomatic diabetic patients undergo routine
      screening for subclinical atherosclerotic disease using myocardial perfusion
      scintigraphy. We herein analyze the expected cost and benefit associated with
      such a conditional test-treatment strategy (scintigraphic testing followed by
      statin treatment in positive test responders) in comparison to an unconditional
      treatment strategy (no testing and statin treatment in all). This analysis shows
      that unconditional treatment is the dominant strategy, costing 24% less ($3.2
      billion) and preventing 25% more (16,800) atherosclerotic events annually on a
      national basis.

PMID- 17498575
TI  - Noninvasive screening for coronary atherosclerosis and silent ischemia in
      asymptomatic type 2 diabetic patients: is it appropriate and cost-effective?
AB  - Coronary artery disease (CAD) accounts for 65% to 80% of deaths in diabetic
      patients. The merits of screening asymptomatic type 2 diabetic patients for
      either (A) the presence of coronary atherosclerosis by imaging of coronary
      calcification using cardiac computed tomography or (B) silent ischemia by stress
      myocardial perfusion imaging (MPI) remain controversial. Some observers have
      advocated for such noninvasive screening in at least the subset of the diabetic
      population who have significant clinical CAD risk factors, so that the highest
      risk patients for future cardiac events can be identified and offered more
      aggressive intensive medical therapy or coronary revascularization and optimum
      medical therapy. Computed tomography coronary calcium scanning could be the first
      noninvasive screening test in these clinically high-risk diabetic patients,
      followed by stress MPI to detect silent ischemia in those who exhibit high
      coronary calcium scores.

PMID- 17498576
TI  - Randomized trial of Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute
      Myocardial Infarction (SESAMI).
AB  - OBJECTIVES: To confirm whether sirolimus-eluting stents (SES) safely reduce the
      incidence of restenosis in patients with ST-segment elevation acute myocardial
      infarction compared with bare-metal stents (BMS). BACKGROUND: In the setting of
      primary angioplasty, stent restenosis occurs in up to 27% of patients. The
      introduction of drug-eluting stents has drastically reduced the incidence of
      restenosis in clinically stable patients. METHODS: We conducted a randomized
      trial of 320 patients with acute ST-segment elevation myocardial infarction
      assigned to receive SES or BMS. The primary end point was binary restenosis at 1
      year angiographic follow-up. RESULTS: At 1 year, the incidence of binary
      restenosis was lower in the SES group than in the BMS group (9.3% vs. 21.3%,
      respectively; p = 0.032), as were the rates of target lesion revascularization
      (4.3% vs. 11.2%; p = 0.02), target vessel revascularization (5% vs. 13.1; p =
      0.015), major adverse cardiac events (6.8% vs. 16.8%; p = 0.005), and target
      vessel failure (8.7% vs. 18.7%; p = 0.007). The incidence of angiographically
      documented stent thrombosis was 1.2% (n = 2) in the SES group and 0.6% (n = 1) in
      the BMS group. CONCLUSIONS: In patients with acute myocardial infarction, SES are
      superior to BMS, reducing the incidence of binary restenosis by 56%, target
      lesion revascularization by 61%, target vessel revascularization by 62%, adverse
      cardiac events by 59%, and target vessel failure by 53% at 1 year. (Sirolimus
      Eluting Stenting in Acute Myocardial Infarction;
      http://www.clinicaltrials.gov/ct/show/NCT00288210; NCT00288210).

PMID- 17498577
TI  - Drug-eluting stents for acute myocardial infarction.

PMID- 17498578
TI  - Genetic variants in P-selectin and C-reactive protein influence susceptibility to
      cognitive decline after cardiac surgery.
AB  - OBJECTIVES: We hypothesized that candidate gene polymorphisms in biologic
      pathways regulating inflammation, cell matrix adhesion/interaction, coagulation
      thrombosis, lipid metabolism, and vascular reactivity are associated with
      postoperative cognitive deficit (POCD). BACKGROUND: Cognitive decline is a common
      complication of coronary artery bypass graft (CABG) surgery and is associated
      with a reduced quality of life. METHODS: In a prospective cohort study of 513
      patients (86% European American) undergoing CABG surgery with cardiopulmonary
      bypass, a panel of 37 single-nucleotide polymorphisms (SNPs) was genotyped by
      mass spectrometry. Association between these SNPs and cognitive deficit at 6
      weeks after surgery was tested using multiple logistic regression accounting for
      age, level of education, baseline cognition, and population structure.
      Permutation analysis was used to account for multiple testing. RESULTS: We found
      that minor alleles of the CRP 1059G/C SNP (odds ratio [OR] 0.37, 95% confidence
      interval [CI] 0.16 to 0.78; p = 0.013) and the SELP 1087G/A SNP (OR 0.51, 95% CI
      0.30 to 0.85; p = 0.011) were associated with a reduction in cognitive deficit in
      European Americans (n = 443). The absolute risk reduction in the observed
      incidence of POCD was 20.6% for carriers of the CRP 1059C allele and 15.2% for
      carriers of the SELP 1087A allele. Perioperative serum C-reactive protein (CRP)
      and degree of platelet activation were also significantly lower in patients with
      a copy of the minor alleles, providing biologic support for the observed allelic
      association. CONCLUSIONS: The results suggest a contribution of P-selectin and
      CRP genes in modulating susceptibility to cognitive decline after cardiac
      surgery, with potential implications for identifying populations at risk who
      might benefit from targeted perioperative antiinflammatory strategies.

PMID- 17498579
TI  - Admission B-type natriuretic peptide levels and in-hospital mortality in acute
      decompensated heart failure.
AB  - OBJECTIVES: This study was designed to determine whether admission B-type
      natriuretic peptide (BNP) levels are predictive of in-hospital mortality in acute
      decompensated heart failure (HF). BACKGROUND: Levels of BNP have been
      demonstrated to facilitate the diagnosis of HF and predict mortality in chronic
      systolic HF. METHODS: B-type natriuretic peptide levels within 24 h of
      presentation were obtained in 48,629 (63%) of 77,467 hospitalization episodes
      entered in ADHERE (Acute Decompensated Heart Failure National Registry). In
      hospital mortality was assessed by BNP quartiles in the entire cohort and in
      patients with reduced (n = 19,544) as well as preserved (n = 18,164) left
      ventricular systolic function using chi-square and logistic regression models.
      RESULTS: Quartiles (Q) of BNP were Q1 (<430), Q2 (430 to 839), Q3 (840 to 1,729),
      and Q4 (> or =1,730 pg/ml). The BNP levels were <100 pg/ml in 3.3% of the total
      cohort. Patients in Q1 versus Q4 were younger, more likely to be women, and had
      lower creatinine and higher left ventricular ejection fraction. There was a near
      linear relationship between BNP quartiles and in-hospital mortality: Q1 (1.9%),
      Q2 (2.8%), Q3 (3.8%), and Q4 (6.0%), p < 0.0001. B-type natriuretic peptide
      quartile remained highly predictive of mortality even after adjustment for age,
      gender, systolic blood pressure, blood urea nitrogen, creatinine, sodium, pulse,
      and dyspnea at rest, Q4 versus Q1 (adjusted odds ratio 2.23 [95% confidence
      interval 1.91 to 2.62, p < 0.0001]). The BNP quartiles independently predicted
      mortality in patients with reduced and preserved systolic function. CONCLUSIONS:
      An elevated admission BNP level is a significant predictor of in-hospital
      mortality in acute decompensated HF with either reduced or preserved systolic
      function, independent of other clinical and laboratory variables. (Registry for
      Acute Decompensated Heart Failure Patients;
      http://www.clinicaltrials.gov/show/NCT00366639; NCT00366639).

PMID- 17498580
TI  - Recurrent unexplained palpitations (RUP) study comparison of implantable loop
      recorder versus conventional diagnostic strategy.
AB  - OBJECTIVES: The aim of the study was to compare the diagnostic yield and the
      costs of implantable loop recorder (ILR) with those of the conventional strategy
      in patients with unexplained palpitations. BACKGROUND: In patients with
      unexplained palpitations, especially in those with infrequent symptoms, the
      conventional strategy, including short-term ambulatory electrocardiogram (ECG)
      monitoring and electrophysiological study, sometimes fails to establish a
      diagnosis. METHODS: We studied 50 patients with infrequent (< or =1
      episode/month), sustained (>1 min) palpitations. Before enrollment, patients had
      a negative initial evaluation, including history, physical examination, and ECG.
      Patients were randomized either to conventional strategy (24-h Holter recording,
      a 4-week period of ambulatory ECG monitoring with an external recorder, and
      electrophysiological study) (n = 24) or to ILR implantation with 1-year
      monitoring (n = 26). Hospital costs of the 2 strategies were calculated. RESULTS:
      A diagnosis was obtained in 5 patients in the conventional strategy group, and in
      19 subjects in the ILR group (21% vs. 73%, p < 0.001). Despite the higher initial
      cost, the cost per diagnosis in the ILR group was lower than in the conventional
      strategy group (euro 3,056 +/- euro 363 vs. euro 6,768 +/- euro 6,672, p =
      0.012). CONCLUSIONS: In subjects without severe heart disease and with infrequent
      palpitations, ILR is a safe and more cost-effective diagnostic approach than
      conventional strategy.

PMID- 17498581
TI  - Platelet surface CD62P and CD63, mean platelet volume, and soluble/platelet P
      selectin as indexes of platelet function in atrial fibrillation: a comparison of
      "healthy control subjects" and "disease control subjects" in sinus rhythm.
AB  - OBJECTIVES: The aim of this work was to comprehensively study the role of
      platelets in atrial fibrillation (AF), in relation to the underlying
      cardiovascular diseases and type of AF, and to analyze the effect of
      antithrombotic treatment on different aspects of platelet activation. BACKGROUND:
      Platelet activation is present in nonvalvular AF, but there is debate whether
      this is due to AF itself and/or to underlying cardiovascular diseases. METHODS: A
      total of 121 AF patients were compared with 65 "healthy control subjects" and 78
      "disease control subjects" in sinus rhythm. Platelet activation was assessed
      using 4 different aspects of platelet pathophysiology: 1) platelet surface
      expression of CD62P (P-selectin) and CD63 (a lysosomal glycoprotein) (by flow
      cytometry); 2) mean platelet volume (MPV) (by flow cytometry); 3) plasma levels
      of soluble P-selectin (sP-selectin, enzyme-linked immunoadsorbent assay); and 4)
      total amount of P-selectin per platelet (pP-selectin) ("platelet lysis" assay).
      RESULTS: Both AF patients and "disease control subjects" had higher levels of
      CD62P (p < 0.001), CD63 (p < 0.001), and sP-selectin (p < 0.001) compared with
      "healthy control subjects," with no difference between AF patients and "disease
      control subjects." Patients with permanent AF had higher levels of sP-selectin (p
      = 0.014) and MPV (p = 0.025) compared with those with paroxysmal AF. The presence
      of AF independently affected the levels of CD62P expression, while "high-risk" AF
      patients (CHADS score > or =2) had higher levels of CD62P compared with those
      with "low risk." Introducing warfarin resulted in a reduction of pP-selectin (p =
      0.013). CONCLUSIONS: There is a degree of excess of platelet activation in AF
      compared with "healthy control subjects," but no significant difference between
      AF patients and "disease control subjects" in sinus rhythm. Platelet activation
      may differ according to the subtype of AF, but this is not in excess of the
      underlying comorbidities that lead to AF. Platelet activation in AF may be due to
      underlying cardiovascular diseases, rather than due to AF per se.

PMID- 17498582
TI  - Using electrocardiographic activation time and diastolic intervals to separate
      focal from macro-re-entrant atrial tachycardias.
AB  - OBJECTIVES: This study was designed to separate focal from atypical macro-re
      entrant atrial tachycardia (AT) on the electrocardiogram (ECG). BACKGROUND: Focal
      AT often cannot be distinguished from macro-re-entrant AT until the time of
      electrophysiology study (EPS). We hypothesized that quantitative ECG metrics
      should separate focal AT, using its short activation relative to tachycardia
      cycle length (CL), from macro-re-entrant AT, whose activation should span the CL.
      We developed tools to accurately quantify CL and P- or F-wave duration even when
      overlying T waves, then prospectively applied them to patients during focal or
      macro-re-entrant AT ablation and compared them to the gold standard EPS
      diagnosis. METHODS: We studied 41 patients (27 men, 14 women) age 57 +/- 17
      years. In the training group (n = 20), tachycardia P or F waves overlying T waves
      were identified from transitions in slope (dV/dt) relative to "expected" T waves
      generated from scaling of the sinus-rate T-wave. Electrocardiographic P-wave
      duration agreed with the duration of intra-atrial activation. Autocorrelation was
      used to estimate ECG atrial CL (p < 0.001). RESULTS: Compared to macro-re-entry
      (n = 13), focal AT (n = 7) had shorter P waves (115 +/- 31 ms vs. 227 +/- 67 ms;
      p < 0.001) that were smaller ratios of CL (28 +/- 7% vs. 85 +/- 21%; p < 0.001).
      Receiver-operating characteristic curve areas for AT were 0.92 for P(F)-wave
      duration and 0.99 for P(F)/CL ratio. On blinded prospective analysis (n = 21),
      P(F)-wave duration <160 ms identified focal (n = 7) from macro-re-entrant AT (n =
      14) with 90% sensitivity and 90% specificity, and a P(F)/CL ratio <45% gave 86%
      sensitivity and 98% specificity. CONCLUSIONS: Quantitative ECG indexes of shorter
      atrial activation and longer diastolic interval separate focal from macro-re
      entrant AT without diagnostic maneuvers.

PMID- 17498583
TI  - Early increase of oxidative stress and soluble CD40L in children with
      hypercholesterolemia.
AB  - OBJECTIVES: The aim of the study was to analyze the behavior of oxidative stress
      and its interplay with CD40L, a protein that is implicated in atherosclerosis, in
      hypercholesterolemic children. BACKGROUND: Oxidative stress has been suggested to
      play a major role in premature atherosclerosis. METHODS: Forty-one children with
      hypercholesterolemia (mean age 9.28 +/- 0.5 years) and 40 children with
      normocholesterolemia (mean age 9.02 +/- 0.69 years) were matched for gender and
      age. Within each group, children were classified as having or not having a family
      history of cardiovascular disease. Serum levels of 8-hydroxy-2'-deoxyguanosine (8
      OHdG), a marker of oxidative stress, and plasma levels of soluble CD40L (sCD40L)
      were measured in each child. In a subgroup of children with high (n = 8) or
      normal (n = 8) levels of serum cholesterol, platelet p38 mitogen-activated
      protein (MAP) kinase phosphorylation, a protein involved in the activation of
      nicotinamide adenine dinucleotide phosphate oxidase, was determined. RESULTS:
      Children with hypercholesterolemia had higher values of 8-OHdG and sCD40L
      compared with control subjects (0.55 +/- 0.06 ng/ml vs. 0.21 +/- 0.02 ng/ml, p <
      0.001 and 0.55 +/- 0.04 ng/ml vs. 0.19 +/- 0.03 ng/ml, p < 0.001, respectively).
      A significant correlation between 8-OHdG and sCD40L was observed in children with
      high (r = 0.676, p < 0.001) or normal (r = 0.878, p < 0.001) levels of
      cholesterol. Children with a family history of cardiovascular disease tended to
      have higher values of 8-OHdG and sCD40L, but the difference was not significant.
      Analysis of platelet p38 MAP kinase showed that it was phosphorylated more in
      children with hypercholesterolemia compared with control subjects (36.8 +/- 5.8
      AU vs. 8.0 +/- 4.5 AU, p < 0.001 respectively). CONCLUSIONS: Children with
      hypercholesterolemia have an early increase of oxidative stress that may be
      responsible for up-regulation of CD40L and potentially predispose to premature
      atherosclerosis.

PMID- 17498584
TI  - Patients with prior myocardial infarction, stroke, or symptomatic peripheral
      arterial disease in the CHARISMA trial.
AB  - OBJECTIVES: The purpose of this study was to determine the possible benefit of
      dual antiplatelet therapy in patients with prior myocardial infarction (MI),
      ischemic stroke, or symptomatic peripheral arterial disease (PAD). BACKGROUND:
      Dual antiplatelet therapy with clopidogrel plus aspirin has been validated in the
      settings of acute coronary syndromes and coronary stenting. The value of this
      combination was recently evaluated in the CHARISMA (Clopidogrel for High
      Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance)
      trial, where no statistically significant benefit was found in the overall broad
      population of stable patients studied. METHODS: We identified the subgroup in the
      CHARISMA trial who were enrolled with documented prior MI, ischemic stroke, or
      symptomatic PAD. RESULTS: A total of 9,478 patients met the inclusion criteria
      for this analysis. The median duration of follow-up was 27.6 months. The rate of
      cardiovascular death, MI, or stroke was significantly lower in the clopidogrel
      plus aspirin arm than in the placebo plus aspirin arm: 7.3% versus 8.8% (hazard
      ratio [HR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01).
      Additionally, hospitalizations for ischemia were significantly decreased, 11.4%
      versus 13.2% (HR 0.86, 95% CI 0.76 to 0.96, p = 0.008). There was no significant
      difference in the rate of severe bleeding: 1.7% versus 1.5% (HR 1.12, 95% CI 0.81
      to 1.53, p = 0.50); moderate bleeding was significantly increased: 2.0% versus
      1.3% (HR 1.60, 95% CI 1.16 to 2.20, p = 0.004). CONCLUSIONS: In this analysis of
      the CHARISMA trial, the large number of patients with documented prior MI,
      ischemic stroke, or symptomatic PAD appeared to derive significant benefit from
      dual antiplatelet therapy with clopidogrel plus aspirin. Such patients may
      benefit from intensification of antithrombotic therapy beyond aspirin alone, a
      concept that future trials will need to validate. (Clopidogrel for High
      Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance
      [CHARISMA]; http://clinicaltrials.gov/ct/show/NCT00050817?order=1; NCT00050817).

PMID- 17498585
TI  - How do I get a paper accepted?--Part 2.

PMID- 17498586
TI  - Simvastatin and plaque inflammation.

PMID- 17498588
TI  - Patients undergoing stabilization surgery for recurrent, traumatic anterior
      shoulder instability commonly have restricted passive external rotation.
AB  - An important component in the surgical treatment of recurrent anterior shoulder
      dislocations is the Bankart repair. This is often supplemented with ligament
      plication for perceived laxity. The glenohumeral ligaments define translational
      laxity and restrict glenohumeral range of motion. The purpose of this study was
      to measure the external rotation (ER) range of motion of patients under
      anesthesia for glenohumeral stabilization surgery. A blinded observer measured
      bilateral shoulder ER in 15 patients by use of a standardized torque and
      goniometry. ER in the unstable shoulder with the arm abducted 90 degrees averaged
      14 degrees less than that in the uninjured shoulder, and this was statistically
      significant. There was a significant loss of 11 degrees ER in the unstable
      shoulder with the arm at the side. The findings indicate that the glenohumeral
      joint in patients with a Bankart lesion is commonly rotationally stiff.

PMID- 17498589
TI  - Superficial primitive neuroectodermal tumor/Ewing sarcoma (PN/ES): same tumor as
      deep PN/ES or new entity?
AB  - Primitive neuroectodermal tumor/Ewing sarcoma (PN/ES) is a single clinical,
      morphologic, and molecular small round cell tumor entity. These are generally
      found in deep soft tissue or bone of young male patients, with poor behavior.
      Location in dermis is unexpected; only rare cases are reported. Cases coded as
      "dermal," "cutaneous," or "skin" PN/ES were retrieved from our consultation
      files. Only primary dermal cases were included. Those otherwise diagnosed or with
      incomplete material were excluded. There were 13 dermal PN/ES cases, consisting
      of 10 women and 3 men. Ages ranged from 2 to 67 years (mean, 28 years). Locations
      included groin or thigh (4), back or shoulder (3), neck (1), chest (1), scalp
      (1), forehead (1), hand (1), and foot (1). Most cases were small (0.5-2.3
      centimeters) and painful, and persisted for less than 1 year. All were located
      within the dermis. Three caused pedunculation; 9 also involved superficial
      subcutis. All but 1 of the metastasizing tumors were round and encapsulated. All
      were composed of round to oval cells with a vague rosetting pattern, slightly
      overlapping nuclei, finely stippled chromatin, clear to eosinophilic cytoplasm,
      and collagenous stroma. Median mitotic activity was 8 per 10 high-power fields.
      Necrosis was present in three cases. All had globular periodic acid Schiff
      positivity and distinctive cytoplasmic membrane CD99 reactivity. One case studied
      was positive for Fli-1. All were negative for leukocyte common antigen, Tdt, CD3,
      CD20, CD79, CK20, pankeratin, epithelial membrane antigen, chromogranin,
      neurofilament protein, carcinoembryonic antigen, desmin, actin, diffuse S100
      protein, and HMB45. Nine cases with material for reverse transcription-polymerase
      chain reaction revealed 1 positive type 2 translocation (EWS exon 7 to Fli-1 exon
      5), 4 negative, and 4 "unable to amplify." Treatment was by wide excision; 9
      received chemotherapy and 6 radiation. Follow-up of 11 (85%) cases revealed the
      following: 1 metastasis to stomach and death at 3 years; 10 years without disease
      (median, 9.0 years). Cutaneous PN/ES is a superficial round cell tumor in older
      women, with better prognosis than deep PN/ES. These may have a hitherto
      unrecognized variant genetic abnormality.

PMID- 17498590
TI  - Melanocytic "ball-in-mitts" and "microalveolar structures" and their role in the
      development of cellular blue nevi.
AB  - To test the hypothesis of whether cellular blue nevi (CBN) may originate from
      "ordinary" compound and dermal nevi, a total of 275 melanocytic nevi including 59
      CBN, 34 ordinary blue nevi, 87 combined nevi (including 43 so-called clonal
      nevi), 35 deep penetrating nevi, and 60 ordinary compound and dermal nevi (30 of
      each) were studied for the presence of so-called ball-in-mitts and microalveolar
      structures. A ball-in-mitts structure was defined as a single centrally placed
      melanocyte with a round to oval nucleus (the "ball" cell) and a clear, dusty, or
      pigmented cytoplasm encircled by a single dendritic cell (the "mitt" cell) with
      an oval to spindle-shaped nucleus and slender bipolar processes containing
      melanin and surrounding at least one fourth of the ball's diameter. A
      microalveolar structure was defined as a group of 2 to 10 centrally placed
      melanocytes with round to oval nuclei and clear, dusty, or pigmented cytoplasm
      (balls) surrounded by one or more cells (mitts) with spindle-shaped nuclei and
      slender bipolar processes containing melanin. Microscopically, ball-in-mitt and
      microalveolar structures were detected in all types of nevi studied, with the
      highest incidence in combined nevi (82%), CBN (76%), and ordinary "nonblue" nevi
      (73%). In CBN, ball-in-mitts and microalveolar structures tended to be located in
      the deeper portion of the lesions, whereas in ordinary nonblue nevi, they were
      most often found superficially, just below the epidermis; in clonal nevi, these
      structures were often confined to the "clonal" parts. Immunohistochemically, ball
      in-mitts and microalveolar structures were positive for HMB45. Ultrastructurally,
      the balls tended to have round to oval nuclei, whereas the mitts possessed oval,
      elongated to spindled nuclei. Melanosomes were found in various stages in the
      cells of both structures. The cytoplasm of the mitts typically formed elongated
      polar processes, sometimes with club-like widenings at the ends, completely or
      partially encircling the balls. In the microalveolar structures, the adjacent
      cells forming the mitts surrounded the ball cells like a chain. Our study
      suggests that some or even most cases of CBN may evolve from ordinary nonblue
      nevi. This process may involve several steps and is probably reflected by the
      appearances of combined nevi, deep penetrating nevi, and CBN. These nevi often
      show a morphological overlap, and ball-in-mitts and microalveolar structures
      found in various stages of their development seem to greatly account for this
      overlap.

PMID- 17498591
TI  - Providing on-site diagnosis of malignancy on endoscopic-ultrasound-guided fine
      needle aspirates: should it be done?
AB  - BACKGROUND: Rapid and accurate tissue diagnosis for a deep-seated malignancy
      would allow treating physicians to provide disease-specific interventions and
      help patients make early informed management decisions. Providing on-site tissue
      diagnosis for fine-needle aspirate samples obtained with endosonography would
      help develop such efficient patient management issues. Here we report our
      experience of prospectively providing on-site diagnosis on 485 endoscopic
      ultrasound fine-needle aspirate samples. METHODS: Four hundred eighty-five
      endoscopic ultrasound fine-needle aspirates from the pancreas (n= 305), lymph
      nodes (n = 91), biliary tree (n = 47), liver (n = 15), gastrointestinal tract (n
      = 19), and adrenal gland (n = 8) were reviewed. For all aspirates, the cytologic
      diagnoses, both preliminary and final, were categorized into the following:
      positive for malignancy, positive for neoplastic process, suspicious for
      malignancy, atypical cells, reactive process, and nondiagnostic. RESULTS: Of the
      485 cases, 163 (33.6%) were diagnosed as benign, 43 (8.8%) as atypical, 21 (4.3%)
      as suspicious, 18 (3.7%) as positive for neoplasm, and 230 (47.4%) as malignant
      after final cytologic interpretation. A significantly (P < .001) higher degree of
      concordance was noted for unequivocal diagnosis of malignancy (196/198, 98.9%) vs
      nonmalignancy (200/250, 67.2%) between on-site and final cytologic diagnosis. Of
      the 52 discordant cases, 12 (2.6%) diagnoses were downgraded and 40 (8.9%) were
      upgraded from preliminary on-site diagnosis. Our overall sensitivity (87 vs 92),
      specificity (95% vs 100%), and accuracy (90% vs 94%) improved for final cytologic
      diagnosis. CONCLUSION: On-site diagnosis of malignancy could be used to initiate
      informed patient management decisions. Cases where a diagnosis of malignancy is
      not rendered at on-site interpretation need further cytologic evaluation.

PMID- 17498592
TI  - Frontotemporal clear cell meningioma. Report of 3 cases.
AB  - Clear cell meningioma (CCM) is an uncommon meningioma. Some cases have been
      reported, and the localization of most of them is the spinal region. We present 3
      cases of CCMs in the frontotemporal lobes. All cases were postmenopausal women
      with a history of arterial hypertension and uterine leiomyomatosis. The
      radiologic appearance in 2 cases was similar to that of dural hematomas, and in 1
      case, the imaging study was consistent with the diagnosis of meningioma. On
      histologic examination, there were sheets of glycogenated polygonal cells with
      abundant clear cytoplasm and round, uniform, bland appearing nuclei. Numerous
      hyalinized blood vessels and collagenous stroma with fibrillary appearance were
      present in 2 cases. They were immunoreactive to epithelial membrane antigen,
      epithelial cell adhesion molecule, and progesterone receptors. However, 2 cases
      showed weak and focal reaction to Her-2/neu. In our knowledge, some cases of CCMs
      have been reported and no immunoexpression has been noted with those markers
      used. These cases illustrate a rare variant of meningioma in the frontotemporal
      lobes and their immunohistochemical profiles. Differential diagnosis is
      discussed.

PMID- 17498593
TI  - Malignant myoepithelial tumor of soft tissue: a report of two cases of the lower
      extremity and a review of the literature.
AB  - Myoepithelial tumors of the soft tissues have only recently been described. Two
      cases of lower extremity malignant myoepithelial tumors are reported. One case of
      malignant mixed tumor overlying the gastrocnemius muscle was treated with wide
      local excision, but metastasized to regional lymph nodes 14 months after surgical
      excision. One patient with malignant myoepithelioma of the right lower leg was
      treated with limb amputation and is alive without disease at 46 months. A review
      of the literature discloses 120 additional cases of soft tissue myoepithelial
      tumors, 102 of which are myoepitheliomas and 18 are mixed tumors. Thirty-seven
      percent of the myoepitheliomas met the criteria for malignancy, and 33% of the
      mixed tumors were malignant. Of these, 30% had locally recurrent disease and 32%
      developed metastatic disease. Treatment benefit from chemotherapy and radiation
      therapy is unclear.

PMID- 17498594
TI  - Ameloblastoma and adenomatoid odontogenic tumor: the role of alpha2beta1,
      alpha3beta1, and alpha5beta1 integrins in local invasiveness and architectural
      characteristics.
AB  - Ameloblastoma is an odontogenic neoplasm characterized by local invasiveness and
      a tendency toward recurrence, whereas adenomatoid odontogenic tumor (AOT) is an
      indolent neoplasm. The objective of the present study was to
      immunohistochemically analyze the role of alpha2beta1, alpha3beta1, and
      alpha5beta1 integrins in the cellular events and cell-matrix interactions that
      occur in these tumors and their consequent repercussions on the architectural
      arrangement and biologic behavior of these lesions. Paraffin-embedded specimens
      from 30 ameloblastomas (20 solid and 10 unicystic tumors) and 12 AOTs were
      submitted to immunohistochemistry using the catalyzed signal amplification
      system. A difference in the pattern of integrin expression was observed between
      the various histologic types of ameloblastoma. No significant difference in
      labeling intensity was observed between unicystic and solid ameloblastomas, but
      comparison between ameloblastomas and AOT showed a significantly stronger
      expression of alpha5beta1 integrin in the former (P < .05). Our findings suggest
      an important role of the integrins studied in the architectural characteristics
      of ameloblastomas and AOTs and a possible participation of alpha5beta1 integrin
      in the mechanism of local invasion of ameloblastomas.

PMID- 17498595
TI  - Microwave-assisted tissue processing: real impact on the histology workflow.
AB  - Tissue processing is just one of many tasks in the histology workflow and
      accounts for 3% to 34% of the total time; it is technology dependent, but all
      other tasks are independent of this step and constitute the remaining 66% to 97%
      of the total time. The best histology workflow is one of fewer than 50 specimen
      loads processed sequentially in the shortest time possible, with postprocessing
      tasks completed in approximately the same time as the preprocessing and
      processing steps combined. Larger loads determine a total workflow too lengthy
      for an efficient continuous operation. This objective may be obtained with
      microwave-assisted instruments or by optimizing conventional instruments usage.
      As a major capital equipment investment, changing technology and selecting an
      instrument should also include a cost-effectiveness analysis.

PMID- 17498596
TI  - Gastrointestinal stromal tumor arising from anorectum: correlation of imprint
      cytology and radiologic imaging.
AB  - The diagnosis of gastrointestinal stromal tumor (GIST) is generally established
      on histopathologic examination of surgical specimens. Gastrointestinal stromal
      tumor comprises a heterogenous group of neoplasms of the gastrointestinal tract
      previously referred to as leiomyomas, leiomyosarcomas, or schwannomas.
      Gastrointestinal stromal tumor arising from anorectum is a rare instance. We
      report a case of GIST for the correlation of imaging and cytologic features with
      immunocytochemical staining. A computed tomography and magnetic resonance imaging
      confirmed a 2-cm tumor growing into the rectal lumen. The central portion of the
      tumor showed T1-weighted imaging of low signal and suspected central necrosis by
      the T2-weighted imaging of high signal. Imprint cytology from excised tumors
      showed isolated or loosely aggregated spindle cells with scanty and fibrillary
      cytoplasmic processes, nuclear pleomorphism, fine granular chromatin, and
      irregular nuclear margins. Epithelioid tumor cells showed grooves with abundant
      cytoplasm and several round nucleoli. Both c-kit and CD34 antigen were positive
      with strong and diffuse stainability in smears as well as paraffin sections by
      immunoperoxidase staining. We suggest that the combined use of imaging diagnosis
      and cytology with immunocytochemical staining are useful initial diagnosis of
      GIST.

PMID- 17498597
TI  - Rectal stenosis caused by foreign body reaction to sodium polystyrene sulfonate
      crystals (Kayexalate).
AB  - Sodium polystyrene sulfonate (SPS) (Kayexalate) is a cation-exchange resin used
      to treat hyperkaliema. Administered with sorbitol, it usually has minor adverse
      effects, but it may cause colonic or intestinal necrosis in uremic patients. We
      report an unusual case of rectal stenosis due to SPS crystals in a 46-year-old
      man. The patient had been involved in a car accident with severe thoracic and
      abdominal trauma. During his hospitalization, he presented traumatic acute
      pancreatitis with ischemic colitis because of hypotension, and acute renal
      insufficiency treated by hemofiltration and Kayexalate administered by
      nasogastric tube without sorbitol. Left colon was resected and Hartmann's
      procedure was performed. Restoration of the colon continuity was performed 13
      months later. The rectal lumen was narrowed with a thickened rectal wall.
      Microscopic examination revealed fibrosis of the submucosa containing numerous
      basophilic polygonal crystals surrounded by macrophages. This is the first case
      report of rectal stenosis caused by foreign body reaction to SPS crystals after
      ischemic colitis.

PMID- 17498598
TI  - Noncrystallized form of immunoglobulin-storing histiocytosis as a cause of
      chronic lung infiltration in multiple myeloma.
AB  - A 52-year-old man, with a known case of multiple myeloma, developed chronic
      bilateral pulmonary infiltration. Open lung biopsy displayed desquamated
      interstitial pneumonia-like pattern characterized by diffused patchy intra
      alveolar accumulation of unusual macrophages containing abundant round
      intracytoplasmic eosinophilic globular structures 1-7 microm in size. The
      globules were stained positively with restriction for kappa light chain by
      immunoperoxidase study. Electron microscopic examination revealed amorphous
      substances without a crystalline shape or fine ultrastructure of lattice or
      linear parallel configuration, indicating storage of noncrystallized
      immunoglobulin. The current report documented, for the first time, the
      noncrystallized form of immunoglobulin-storing histiocytosis, causing an unusual
      pulmonary pathology in a patient with multiple myeloma.

PMID- 17498599
TI  - Synovial sarcoma of the larynx in a 79-year-old woman, confirmed by karyotyping
      and fluorescence in situ hybridization analysis.
AB  - BACKGROUND: Synovial sarcoma is an uncommon tumor of the head and neck and is an
      exceedingly rare finding in the larynx. Generally, it afflicts younger patients
      and most often occurs in the hypopharynx. METHODS AND RESULTS: We report a case
      of a biphasic synovial sarcoma arising in the arytenoid fold of a 79-year-old
      woman. The diagnosis was confirmed by an extensive immunohistochemical panel,
      karyotyping, and fluorescence in situ hybridization (FISH). The patient was
      treated with total laryngectomy, and she did well postoperatively. CONCLUSION: To
      our knowledge, our patient is the oldest ever to be reported in the literature,
      concluding that although this entity is considered a disease of young patients,
      it still has to be included in the differential diagnosis in older patients.
      Second, our report is only the third to describe t(X;18) (p11.2;q11.2) by
      karyotyping and the first ever by using FISH analysis, thus adding more
      cytogenetic data to the literature in this rare location and confirming the use
      of FISH in making the accurate diagnosis.

PMID- 17498600
TI  - Trophogram, an immunohistochemistry-based algorithmic approach, in the
      differential diagnosis of trophoblastic tumors and tumorlike lesions.
AB  - Recent histopathologic and molecular studies of trophoblastic cells in the normal
      placenta and in a variety of trophoblastic diseases have revealed that the latter
      recapitulate the differentiation of normal trophoblast in the early developing
      placenta. This new knowledge, especially the identification and characterization
      of the protein markers expressed in human trophoblast, not only helps elucidate
      the pathogenesis of trophoblastic lesions but also provides a repertoire of
      immunohistochemical markers that may facilitate the diagnosis of various
      trophoblastic diseases. This article reviews the recent advances in the
      trophoblast-associated markers that have been reported to be useful in the
      differential diagnosis of trophoblastic tumors and tumorlike lesions. Moreover, a
      "trophogram," which is a stepwise and rational immunohistochemistry-based
      approach, will be introduced. The trophogram may prove to be useful in assisting
      the differential diagnosis of various trophoblastic diseases in diagnostic
      pathology.

PMID- 17498601
TI  - Weight loss in the nursing home.

PMID- 17498602
TI  - Tube feeding in dementia: how incentives undermine health care quality and
      patient safety.
AB  - For nursing home residents with advanced dementia, very little evidence is
      available to show clinical benefit from enteral tube feeding. Although no
      randomized clinical trials have been done, considerable evidence from studies of
      weaker design strongly suggest that tube feeding does not reduce the risks of
      death, aspiration pneumonia, pressure ulcers, other infections, or poor
      functional outcome. Nationally, however, utilization is high and highly variable.
      System-wide incentives favor use of tube feeding, and may influence substitute
      decision-makers, bedside clinicians, gastroenterologists, and administrators
      regardless of patient preferences or putative medical indications. Underlying the
      widespread use of this marginally effective therapy is a basic misunderstanding
      about malnutrition and about aspiration pneumonia. The face value of tube feeding
      is strong indeed. In addition to the general faith in intervention, the impulse
      to "do something" when things are going poorly, financial incentives favor tube
      feeding for gastroenterologists, hospitals, and nursing homes. The desire to
      avoid regulatory sanctions, bad publicity, and liability exposure creates a
      further incentive for nursing homes to provide tube feeding. Rational, evidence
      based use of tube feeding in advanced dementia will depend fundamentally on
      improved education. Reimbursement schemes require significant modification to
      limit the irrational use of tube feeding. Nursing home regulations based more
      securely on scientific evidence would likely reduce nonbeneficial tube feeding,
      as would evidence-based tort reform. Quality improvement initiatives could create
      positive incentives. Realigning incentives in these ways could, we believe,
      improve the quality of care, quality of life, and safety of these vulnerable
      individuals, likely with reduced costs of care.

PMID- 17498603
TI  - Constipation in long-term care.
AB  - Constipation is more common in older adults and accounts for increased physician
      office visits and hospital admissions. There is lack of agreement on the
      definition of constipation regarding what patients perceive as constipation and
      what physicians traditionally see as constipation. Constipation is related to
      multiple factors, and when left untreated or not properly treated, results in
      complications, such as impaction, even perforation and death. Laxative use
      increases with age and at times multiple agents are used to relieve symptoms of
      constipation. Currently the most commonly used laxative is stool softener but it
      lacks efficacy. From the review of literature, osmotic laxatives are effective in
      older adults and well tolerated. Psyllium, a bulk laxative, is also effective in
      the treatment of constipation, while there is limited evidence for stimulants,
      dioctyl sulfosuccinate, and other bulk laxatives such as calcium polycarbophil
      and methylcellulose. A new drug, lubiprostone, is a type 2-chloride channel
      activator and is shown to be effective, safe, and well tolerated in older adults
      treated for chronic constipation in studies up to a year. It appears to be
      particularly useful in persons who have recurrent fecal impaction and in those
      with severe chronic constipation. There is a need for a large-scale trial
      examining an appropriate cost-effective approach to the management of
      constipation in the nursing home.

PMID- 17498604
TI  - Gynecologic care of elderly women.
AB  - Evaluation and management strategies for addressing abnormal bleeding, discharge,
      urinary symptoms, and sexuality amongst elderly women are presented.

PMID- 17498605
TI  - Advance directives at end-of-life: nursing home resident preferences for
      artificial nutrition.
AB  - OBJECTIVE: Nursing homes are increasingly the place where many Americans die.
      Thus, advance directives are critical to the preservation of the autonomous
      wishes at end-of-life. The purpose of this paper is to determine if preferences
      for artificial nutrition, as stated in the advance directives of nursing home
      residents, are honored in the last 2 months of life. DESIGN: Secondary analysis.
      SETTING: Six Maryland community nursing homes. PARTICIPANTS: Fifty-seven
      consented residents (age 62 to 98) from the parent study who died during the
      study period. MEASUREMENTS: Retrospective document review including advance
      directives and clinical care provided in the last 2 months of life. RESULTS: Most
      of the nursing home residents in this sample refused feeding tubes, and these
      preferences were honored during the last 2 months of life (93%), despite some
      (17% to 26%) with documented weight loss. A small percentage (8.8%) of residents
      received feeding tubes at end-of-life and, of those, only 1 was consistent with
      advance directive preferences. Most advance directives in this study included
      feeding tube preferences. CONCLUSION: In this nursing home sample, advance
      directives were significant documents guiding decisions on artificial nutrition,
      and feeding tubes were in fact uncommon at the end of life. The study suggests
      that advance care planning, quality palliative care training, and administrative
      support are necessary for the honoring of preferences. Future research is needed
      to examine more broadly tube-feeding practices and prevalence in nursing homes.

PMID- 17498606
TI  - The use of hip protectors in long-term care facilities: a survey of nursing home
      staff.
AB  - OBJECTIVES: To determine the level of exposure to hip protectors and barriers to
      their use in nursing homes. DESIGN, SETTING, AND PARTICIPANTS: We conducted a
      written survey of 160 staff (including administrators) in 5 nursing homes in the
      Hamilton-Wentworth region, Ontario, Canada. MEASUREMENTS: The results of primary
      analyses were expressed as percentage of respondents. RESULTS: Among respondents
      of respective institutions, the rate of prior exposure to hip protectors varied
      from 40.9% to 100.0% and the rate of prior experience applying these devices
      varied from 14.3% to 80.0%. The most frequently cited main barriers to the use of
      hip protectors in long-term care facilities included physicians not thinking to
      prescribe them, expense, lack of evidence of benefit in this population, wearer
      discomfort, and wearer removal. A lack of staff time to apply these devices was
      rarely cited. The majority of staff believed that nursing home residents with a
      prior history of fracture, those who fall frequently, or those who are unsteady
      on their feet should wear hip protectors. CONCLUSIONS: The exposure of surveyed
      nursing home staff to hip protectors was variable but most agreed that residents
      who are at increased risk of hip fracture should wear them. Some identified
      barriers to the use of hip protectors in long-term care facilities were
      physicians not thinking to prescribe them, expense, lack of evidence of benefit
      in this population, wearer discomfort, and wearer removal. Such barriers need to
      be addressed for hip protector implementation strategies to be successful in
      nursing homes.

PMID- 17498607
TI  - Predictors of rehabilitation outcomes: a comparison of Israeli and Italian
      geriatric post-acute care (PAC) facilities using the minimum data set (MDS).
AB  - OBJECTIVES: To understand the relative contribution of sociodemographic,
      clinical, and health care features to rehabilitation outcomes in Israel and in
      Italy in post-acute care (PAC) facilities. DESIGN: Prospective cross-national
      study SETTING: Two hospital geriatric PAC departments: Harzfeld Geriatric
      Hospital, Gedera, Israel, and Catholic University of Sacred Heart Geriatric
      Hospital, Rome, Italy. PARTICIPANTS: Post-acute care patients aged 65 and older
      admitted consecutively for stabilization, improvement, or rehabilitation to 3
      departments in Harzfeld Geriatric Hospital, Gedera, Israel from April, 1999
      through February, 2002 (N = 364), and to the post-acute Geriatric Rehabilitation
      Unit of the "A. Gemelli" Hospital, Catholic University of Sacred Heart, Rome,
      Italy, between February, 1999, and April, 2002 (N = 351), for whom there were
      complete assessments at admission and discharge (the total number admitted in
      Israel was 505, and in Italy, 409). MEASUREMENTS: Minimum Data Set for Post-Acute
      Care (MDS-PAC) assessments conducted within 4 days of admission and at discharge;
      data collected identically in both sites. Predictors of functional recovery> were
      identified using multivariate binary logistic regression. The dependent variable:
      improvement of 1 or more points in the ADL scale. RESULTS: The staffing pattern
      of the PAC department in Italy had about double the physicians and physio- and
      occupational therapists than in Israel, but about the same number of nurses and
      somewhat fewer aides than in Israel. Multivariate binary logistic regression that
      includes country, age, sex, and marital status, found that the patients in Italy
      had about triple the probability of improvement in ADL function (OR 3.3, CI 2.4
      4.6) (P < .001) than PAC patients in Israel. Even after health system
      characteristics were added to the model, ADL improvement was most significantly
      associated with higher cognitive ability and a diagnosis of hip fracture, as well
      as longer length of stay and being admitted to PAC directly from an acute
      hospital. For each additional point (worse cognition) in a cognitive scale, there
      was a 30% decrease in the probability of ADL improvement (OR 0.7, CI 0.6-0.8, P <
      .001). Those who had a stroke were about half as likely to show ADL improvement
      (OR 0.5, CI 0.3-0.7) than those without stroke, but those with a hip fracture had
      more than double the probability of ADL improvement (OR 2.7, CI 1.7-4.2) than
      those without hip fracture. Those who stayed in the PAC ward an additional block
      of time had a 30% higher probability of ADL improvement (P < .1), and those who
      were admitted directly to PAC from an acute hospital had more than 4 times the
      probability of ADL improvement (OR 4.1, CI 2.3-7.0, P < .001) than those who were
      admitted from a private home. CONCLUSIONS: We found support for the hypothesis
      that differences in sociodemographic and clinical factors cannot account for all
      differences in ADL improvement, and that the organization of care and constraints
      of the health system also influence functional outcomes. Policymakers should
      examine the policy-amenable features of the Italian and Israeli systems so that
      optimal ADL recovery can be encouraged. Any reduction in disability will help
      both patients and the health care system; slightly higher short-term PAC
      treatment costs may have large long-term future benefits, if they result in the
      reduction of ADL disability. This study is one of the first to examine outcomes
      of PAC in 2 countries, and can provide an initial assessment of how
      rehabilitation can be enhanced or limited by health policies and staffing
      patterns.

PMID- 17498608
TI  - The use of a cholinesterase inhibitor review committee in long-term care.
AB  - OBJECTIVE: The objective of the study was to document the effectiveness of a
      Cholinesterase Inhibitor (ChE-I) Review Committee in a long-term care (LTC)
      institution in Montreal, Canada. DESIGN: Retrospective cohort study. SETTING:
      Maimonides Geriatric Centre (MGC), a 387-bed LTC facility in Montreal, Canada, in
      which 352 patients have dementia. PARTICIPANTS: Fifty-two patients on ChE-I who
      were reviewed at least once by the ChE-I Review Committee between January and
      November 2005. MEASUREMENTS: Recommendations for discontinuation, actual
      discontinuation, and restarting of ChE-I, along with reasons underlying these
      decisions, were collected from the patients' charts over a 4-month period
      following Review Committee assessment. RESULTS: The Review Committee recommended
      discontinuation of ChE-I in 17 (32.7%) of the 52 patients. After 1 patient died
      and therefore was excluded from the study, 13 (81.3%) of the remaining 16 were
      actually discontinued. The most common reasons for recommendation to discontinue
      ChE-I were insufficient benefit on cognition, activities of daily living (ADL),
      and behavior. Subsequently, ChE-I was resumed in 4 (30.8%) of the 13 patients
      discontinued, 2 because of ADL deterioration and 2 at the request of the family.
      CONCLUSIONS: Through the review process, almost one third of ChE-I users were
      recommended for discontinuation because of insufficient benefit; the majority of
      these were discontinued. Fewer than one third were subsequently restarted. A ChE
      I Review Committee seemed to be an effective and acceptable model for decision
      making regarding ChE-I use in LTC.

PMID- 17498609
TI  - Do herbal agents have a place in the treatment of sleep problems in long-term
      care?
AB  - Sleep disruption is common in the long-term care setting. This article discusses
      the available literature on 2 herbal approaches to sleep problems in long-term
      care. The largest body of evidence exists for the use of the dietary/herbal
      supplements valerian and melatonin. While these agents appear to have a modest
      positive effect on sleep quality among older adults, most studies were small in
      size and included only subjective assessments of sleep quality. In addition, it
      is unclear whether these agents pose risks to long-term care residents because of
      potential drug interactions. Additional research is needed before making
      conclusive recommendations about the use of these interventions for sleep in the
      long-term care setting.

PMID- 17498610
TI  - Introducing a new incontinence management system for nursing home residents.
AB  - OBJECTIVES: To describe current practices of incontinence care in nursing homes
      (NHs) provided by certified nurse assistants (CNAs), and to evaluate the
      feasibility and acceptability of an integrated incontinence care product, the One
      Step Incontinence System (OSIS) in the NH setting. While the ultimate purpose of
      OSIS is to encourage more consistent skin cleansing and thus reduce perineal
      dermatitis and risk of pressure ulcers, this study reports an initial feasibility
      test of OSIS. DESIGN: Controlled trial at two NH sites, with one ward at each
      site assigned to intervention with OSIS and one ward at each site assigned to a
      control condition with a box of wipes placed at the bedside (BW). SETTING: Two
      NHs (one community and one Veterans Administration) in the Los Angeles area.
      PARTICIPANTS: 24 incontinent NH residents and 61 CNAs. INTERVENTION: OSIS
      integrates an adult brief and two cleansing/protective wipes into a single item
      by way of a waterproof pouch that is removed at the time of incontinence care.
      The OSIS briefs were placed on the intervention wards in the same location(s) and
      adjacent to regular adult briefs. MEASUREMENTS: Structured observations of
      incontinence care episodes were performed by trained research staff at baseline
      on all wards, and at follow-up with either the intervention (OSIS) or control
      condition (BW) in place. Observations included resident location, thoroughness
      and duration of incontinence care, and materials used. In addition, CNAs'
      opinions of their preferred incontinence care materials and their experience
      using OSIS were obtained by self-administered survey. RESULTS: Use of OSIS
      resulted in significantly greater frequency of use of cleansing wipes (97% of
      episodes) compared to the baseline (77% of episodes) and BW conditions (41% of
      episodes). In 59% of the observed episodes in the BW condition, the box of wipes
      was actually missing from the bedside, or completely absent from the patient's
      room and had to be replaced. The two wipes that were incorporated with OSIS were
      used for perineal skin cleansing immediately when providing incontinence care.
      There was a significant reduction in the percentage use of and number of cloth
      towels used during incontinence care with OSIS (53% of episodes, 0.8 towels)
      compared to baseline (67%, 1.1 towels) and BW conditions (82%, 1.2 towels; p=.002
      and p=.012, respectively). CNAs were significantly less often interrupted by the
      need to find supplies during OSIS condition (13%) compared to baseline (23%) and
      BW (36%; p= .005). There were no significant differences between conditions in
      the thoroughness of observed cleansing. The average observed time for
      incontinence care from putting on gloves to fastening the clean adult brief (T1)
      and between uncovering the resident to fastening a clean adult brief (T2)
      decreased significantly within both groups (OSIS and BW) at follow-up (all p
      values <.05), but there were no significant differences in T1 and T2 between
      groups at follow-up. CNAs were more likely to report that they felt that OSIS
      facilitated skin cleansing compared to the BW. CONCLUSION: We successfully
      implemented a trial of an innovative adult brief that encouraged skin cleansing
      during incontinence care. The system was easily and effectively incorporated into
      the nursing home, was used by CNAs whenever available (97% of the time), and was
      favored by CNAs. Patterns of incontinence care differed at follow-up with OSIS
      compared to BW, with fewer linens used, fewer wipes used, and less CNA
      interruption during care, which may result in greater privacy and comfort for
      residents.

PMID- 17498611
TI  - Overmedicating "difficult" patients.

PMID- 17498612
TI  - Working with families in long-term care.
AB  - Effective communication with families can improve clinical process and outcomes
      in long-term care. Such communication may be challenging to long-term care
      clinicians, who may feel they lack requisite skills or are uncomfortable with
      potentially charged and negative emotions that may result. These barriers can be
      overcome by using models of family behavior and of physician involvement in
      family counseling to foster understanding and organize family meetings. We
      present such models in this article. The first of these, the Pearlin Stress
      Process Model offers a framework for understanding family adaptation to long-term
      care. Within the Pearlin model, family function is a critical intervening
      variable. Structural Family Systems Theory is therefore examined next to guide to
      recognition of family characteristics that impact communication. We focus on
      translation of these theories to long-term care practice through clinical case
      vignettes. Applying the Levels of Physician Involvement in family oriented care
      to long-term care, we then suggest an organizing, stepwise process for the family
      meeting itself. We conclude with strategies for conflict management and a
      discussion of the importance of the interdisciplinary team in family care.

PMID- 17498613
TI  - Biostatistics note: more could be done in predicting nursing home admission using
      the Cox proportional hazards model.

PMID- 17498614
TI  - Hypotensive syncope in a wheelchair.

PMID- 17498616
TI  - Cloning of novel tumor metastasis-related genes from the highly metastatic human
      lung adenocarcinoma cell line Anip973.
AB  - A cDNA library was successfully constructed from Anip973, a human lung
      adenocarcinoma cell line with high metastatic potential. NIH3T3 cells were stably
      transfected using this cDNA library and screened for morphological changes in a
      soft agar assay. Genomic DNA was isolated from putative clones and the integrated
      sequence was retrieved by PCR and sequencing. Three known genes, ribosomal
      protein L23, hypothetical protein FLJ22104, and serine protease inhibitor, kazal
      type 6 and a number of 5'-terminally truncated sequences were identified.
      Furthermore, cells transfected with ribosomal protein L23 was highly invasive
      compared with the empty vector as control (P<0.02). These results indicate that
      the expression cloning of cDNA libraries in NIH3T3 cells and subsequent screening
      for loss of contact inhibition in soft agar is a viable tool for identifying
      tumor-related genes and ribosomal protein L23 gene plays a role in cell movement
      and metastasis.

PMID- 17498617
TI  - Research on the karyotype and evolution of Drosophila melanogaster species group.
AB  - Mitotic metaphase chromosomes of 34 species of Drosophila melanogaster species
      group were examined. Certain new karyotypes were described for the first time,
      and their evolutionary and interspecific genetic relationships among 8 subgroups
      of D. melanogaster species group were analyzed systematically. The results were
      as follows. The basic karyotype of elegans subgroup was type A. The karyotypes of
      eugracilis subgroup, melanogaster subgroup, and ficusphila subgroup were all type
      C. The karyotypes of takahashii subgroup and suzukii subgroup were both type C
      and type D. The montium subgroup had six kinds of karyotypes: types B, C, C', D,
      D', and E. The ananassae subgroup had three kinds of karyotypes: types F, G, and
      H. Thus, the melanogaster species group was classified into five pedigrees based
      on the diversity of these karyotypes: 1) elegans; 2) eugracilis-melanogaster
      ficusphila; 3) takkahashii-suzukii; 4) montium; 5) ananassae. The above-mentioned
      results in karyotypic evolution were consistent with those of DNA sequence
      analysis reported by Yang except for the elegans subgroup and this subgroup was
      considered as the ancestral subgroup. Karyotype analysis of the same drosophila
      from different isofemale lines indicated that the same Drosophila from different
      places showed karyotypic variation which might be due to different geographical
      environment and evolutionary degree or interaction between the two factors.

PMID- 17498618
TI  - Microsatellite genotyping for four expected inbred mouse strains from KM mice.
AB  - Chinese Kun Ming (KM) mouse, an outbreed strain of laboratory animal, has been
      widely utilized in related pharmaceutical and genetic studies throughout China.
      However, the value of KM mice to the research community has been severely
      limited, partially due to the fact that well-characterized inbred strain of KM
      mice is not available. Several expected inbred strains from KM mice have been
      bred, but their genetic purity remains uncertain. In this study, four expected
      inbred strains of KM mice (A1, T2, N2, and N4) were chosen and their inbred
      degree were compared with two classical inbred mouse lines (BALB/c and C57BL/6)
      by analyzing the genotypes of about 30 microsatellite markers. In the four
      strains, A1 and N4 were homozygous at all genotyped loci, but N2 and T2 were only
      heterozygous at locus D15Mit16. These results indicate that the level of genetic
      purity/homozygousity of A1, N4, N2, and T2 inbred line is comparable to those of
      BALB/c and C57BL/6. This study provided the first and solid evidence for genetic
      purity of four expected inbred strains of KM mice. These 4 inbred mice strains
      should be well maintained for further characterization and utilization in genetic
      studies.

PMID- 17498619
TI  - Developmental changes of Col3a1 mRNA expression in muscle and their association
      with intramuscular collagen in pigs.
AB  - Eighty-four castrated boars including Laiwu Black (LW) (weight 30-90 kg, n=6) and
      Lulai Black (LL) (weight 40-100 kg, n=6) were used to study the developmental
      changes of collagen type III alpha 1 (Col3a1) mRNA expression in the muscle and
      their association with intramuscular collagen (IMC). The muscle total RNA was
      extracted to determine the abundance of Col3a1 mRNA using relative quantitative
      RT-PCR with beta-actin mRNA as the internal standard. The results indicated that
      the developmental patterns of muscle Col3a1 mRNA in LW and LL pigs were similar.
      The abundance of Col3a1 mRNA increased with body weight, but decreased a little
      at 70 kg and 80 kg phases for LW and LL, respectively. On the whole, the
      expression level of Col3a1 mRNA in muscle of LW was higher than that of LL
      (P<0.05). Correlation analysis showed that the expression of Col3a1 mRNA in
      muscle was positively correlated with total and insoluble IMC, but was negatively
      correlated with IMC solubility for LW pigs (P<0.01) and LL pigs (P<0.05),
      respectively. These results suggest that the muscle Col3a1 gene expression is
      affected by body weight and genotype and has important effect on IMC content and
      characteristics.

PMID- 17498620
TI  - A Nucleus-encoded topological specificity factor PpMinE in Physcomitrella patens
      has conserved function similar to its chloroplast-encoded ancestor.
AB  - A nucleus-encoded MinE gene, designated PpMinE, from Physcomitrella patens was
      identified using RT-PCR. The presence of both N- and C-terminal extensions in
      PpMinE protein suggested its cyanobacterial origin. The transient expression of
      PpMinE using green fluorescent protein fusion in tobacco (Nicotiana tabacum L.)
      indicated that the PpMinE was a chloroplast-targeted protein. Overexpression of
      PpMinE in Escherichia coli caused division site misplacement and minicell
      formation, suggesting evolutionary functional conservation of MinE during plant
      phylogenesis. According to the phylogenetic tree, PpMinE protein has a close
      relationship with the highland plants, which suggests that the transfer events of
      MinE gene from plastid to nucleus might have occurred before the origin of the
      land plants.

PMID- 17498621
TI  - Identification of quantitative trait loci for cold response of seedling vigor
      traits in rice.
AB  - The quantitative trait loci (QTLs) for the seedling vigor traits under 12 degrees
      C cold water irrigation, such as the seedling height, the seedling fresh weight,
      the seedling dry weight, and their cold response index, were identified using an
      F(2/3) population including 200 individuals and lines derived from a cross of
      indica and japonica "Milyang 23/Jileng 1" with microsatellite markers. All
      seedling vigor traits exhibited a continuous distribution near normal in F3
      lines; these traits were quantitative traits controlled by multiple genes. Twelve
      QTLs conferring the seedling vigor traits under cold water irrigation were
      detected on chromosomes 1, 2, 7, 8, and 12, which explained the observed
      phenotypic variance from 5.2% to 17.9%. Among them, qCSH2 and qCSH12 were located
      in RM262-RM263 on chromosome 2 and RM270-RM17 on chromosome 12, respectively,
      which were associated with the seedling height. qSDW12 and qCSDW1 were located in
      RM19-RM270 on chromosome 12 and RM129-RM9 on chromosome 1, respectively, which
      were correlated with the seedling dry weight and its cold response index, and the
      explained 16.6%, 17.9%, 15.9%, and 16.2% of the observed phenotypic variation,
      respectively. These QTLs alleles were derived from cold-tolerant parent Jileng 1;
      the gene actions of the two front genes showed their additive effect, and the two
      genes blind showed dominant and over dominant effects, respectively.

PMID- 17498622
TI  - Genome-wide detection and analysis of alternative splicing for nucleotide binding
      site-leucine-rich repeats sequences in rice.
AB  - Alternative splicing is a major contributor to genomic complexity and proteome
      diversity, yet the analysis of alternative splicing for the sequence containing
      nucleotide binding site and leucine-rich repeats (NBS-LRR) domain has not been
      explored in rice (Oryza sativa L.). Hidden Markov model (HMM) searches were
      performed for NBS-LRR domain. 875 NBS-LRR-encoding sequences were obtained from
      the Institute for Genomic Research (TIGR). All of them were used to blast
      Knowledge-based Oryza Molecular Biological Encyclopaedia (KOME), TIGR rice gene
      index (TGI), and Universal Protein Resource (UniProt) to obtain homologous full
      length cDNAs (FL-cDNAs), tentative consensus sequences, and protein sequences.
      Alternative splicing events were detected from genomic alignment of FL-cDNAs,
      tentative consensus sequences, and protein sequences, which provide valuable
      information on splice variants of genes. These sequences were aligned to the
      corresponding BAC sequences using the Spidey and Sim4 programs and each of the
      proteins was aligned by tBLASTn. Of the 875 NBS-LRR sequences, 119 (13.6%)
      sequences had alternative splicing where multiple FL-cDNAs, TGI sequences and
      proteins corresponded to the same gene. 71 intron retention events, 20 exon
      skipping events, 16 alternative termination events, 25 alternative initiation
      events, 12 alternative 5' splicing events, and 16 alternative 3' splicing events
      were identified. Most of these alternative splices were supported by two or more
      transcripts. The data sets are available at http://www.bioinfor.org Furthermore,
      the bioinformatics analysis of splice boundaries showed that exon skipping and
      intron retention did not exhibit strong consensus. This implies a different
      regulation mechanism that guides the expression of splice isoforms. This article
      also presents the analysis of the effects of intron retention on proteins. The C
      terminal regions of alternative proteins turned out to be more variable than the
      N-terminal regions. Finally, tissue distribution and protein localization of
      alternative splicing were explored. The largest categories of tissue
      distributions for alternative splicing were shoot and callus. More than one
      thirds of protein localization for splice forms was plasma membrane and
      cytoplasm. All the NBS-LRR proteins for splice forms may have important function
      in disease resistance and activate downstream signaling pathways.

PMID- 17498623
TI  - Rice repetitive DNA sequence RRD3: a plant promoter and its application to RNA
      interference.
AB  - Previously, a moderately repetitive DNA sequence (RRD3) was cloned from rice
      (Oryza sativa L.) by DNA renaturation kinetics. Sequence analysis revealed
      several conserved promoter motifs, including four TATA-boxes and a CAAT-box, and
      promoter activity was shown in Escherichia coli and mammalian expression systems.
      Here, we inserted the RRD3 fragment into the plant promoter-capture vector,
      pCAMBIA1391Z, and examined whether the RRD3 fragment has promoter activity in
      plants. Transgenic tobacco and rice calli both showed beta-glucuronidase (GUS)
      activity, indicating that RRD3 can act as a promoter in both monocot and dicot
      plants. Based on the promoter characteristic of RRD3, we designed a plant
      universal binary vector, pCRiRRD3, which is suitable for performing researches on
      plant RNA interference. This vector has two multiple cloning sites to facilitate
      sense and antisense cloning of the target sequence, separated by an intron
      fragment of 200 bp. The efficiency of the vector for gene silencing was assayed
      by histochemical and quantitative fluorometric GUS assays in transgenic tobacco.
      These research results suggested that this plant RNAi vector pCRiRRD3 can
      effectively perform gene silencing researches on both monocot and dicot plants.

PMID- 17498624
TI  - Cloning and expression analysis of PtFATB gene encoding the acyl-acyl carrier
      protein thioesterase in Populus tomentosa Carr.
AB  - Acyl-ACP thioesterases (FATs) terminates the fatty acid synthesis and allow the
      transport of fatty acids out of the plastids, which are the important
      determinants of cellular metabolism. FATB is a member of FAT enzymes that has
      been described previously in most of the plants. In silico cloning is a new
      method that utilizes the bioinformatics on the complete genome and available EST
      database. In this study, a full-length cDNA clone of PtFATB gene was isolated
      from Populus tomentosa using this approach. It is 1,450 bp in length and the open
      reading frame encodes a peptide of 421 amino acids. The predicted amino acid
      sequence shows significant homology with those from other plant species, which
      contain typical domains owned by FATB proteins. The transcripts of PtFATB were
      abundant in leaves, and less in roots detected by using semiquantitative RT-PCR.
      When the shoots were subjected to the stress treatments (cold, dry, NaCl) and ABA
      (Abscisic acid), the expression of PtFATB was only slightly reduced under the
      treatment of low temperature. This suggests that the expression of PtFATB is in a
      constitutive fashion. This study provides the basis not only for the
      identification and characterization of this gene but also for the improvement of
      cold tolerance by controlling the expression of the PtFATB gene in trees in near
      future.

PMID- 17498625
TI  - Analysis of synonymous codon usage in Aeropyrum pernix K1 and other Crenarchaeota
      microorganisms.
AB  - In this study, a comparative analysis of the codon usage bias was performed in
      Aeropyrum pernix K1 and two other phylogenetically related Crenarchaeota
      microorganisms (i.e., Pyrobaculum aerophilum str. IM2 and Sulfolobus
      acidocaldarius DSM 639). The results indicated that the synonymous codon usage in
      A. pernix K1 was less biased, which was highly correlated with the GC(3S) value.
      The codon usage patterns were phylogenetically conserved among these
      Crenarchaeota microorganisms. Comparatively, it is the species function rather
      than the gene function that determines their gene codon usage patterns. A. pernix
      K1, P. aerophilum str. IM2, and S. acidocaldarius DSM 639 live in differently
      extreme conditions. It is presumed that the living environment played an
      important role in determining the codon usage pattern of these microorganisms.
      Besides, there was no strain-specific codon usage among these microorganisms. The
      extent of codon bias in A. pernix K1 and S. acidocaldarius DSM 639 were highly
      correlated with the gene expression level, but no such association was detected
      in P. aerophilum str. IM2 genomes.

PMID- 17498626
TI  - Effects of SHIP-1 on MMP2 secretion and invasion of SR3Y1 cells.
AB  - SHIP-1 is an SH2 domain containing inositol-5-phosphatase that appears to be a
      negative regulator of hematopoiesis. To the potential effects of SHIP-1 on MMP2
      secretion and migration of cancer cells, three murine SHIP-1 mutants were made:
      DeltaSH2-SHIP-1, DeltaPtase-SHIP-1, DeltaCter-SHIP-1. These mutant forms were
      subcloned as well as the wild type (WT) of murine SHIP-1 cDNA were subcloned into
      pcDNA3 expression vector, then transfected into and overexpressed SHIP-1 and its
      mutants in a Src-transformed 3Y1 cell line (SR3Y1). The results showed that
      overexpression of wild type of SHIP-1 does not affect the MMP2 secretion in both
      SR3Y1 and 3Y1 cells, but can induce MMP9 secretion, while either WT SHIP-1, the
      SH2 domain, phosphatase domain, or C terminus deletion mutants could
      significantly block the MMP2 and MMP9 secretion in SR3Y1 cells and suppress cell
      invasion ability. The results confirmed SHIP-1 as a negative regulator for cell
      migration and invasion in transformed cells, and implied that it may function
      through each of its three domains.

PMID- 17498627
TI  - Phylogenetic reconstruction of the family Acrypteridae (Orthoptera: Acridoidea)
      based on mitochondrial cytochrome B gene.
AB  - Sequences from the mitochondrial cytochrome b gene (Cyt b) were determined for 25
      species from the superfamily Acridoidae and the homologous sequences of 19
      species of grasshoppers were downloaded from the GenBank data library. The
      purpose was to develop a molecular phylogeny of the Acrypteridae, and to
      interpret the phylogenetic position of the family within the superfamily
      Acridoidea. Phylogeny was reconstructed by Maximum-parsimony (MP) and Bayesian
      criteria using Yunnanites coriacea and Tagasta marginella as outgroups. The
      alignment length of the fragments was 384 bp after excluding ambiguous sites,
      including 167 parsimony informative sites. In the fragments, the percentages of A
      + T and G + C were 70.7% and 29.3%, respectively. The monophyly of Arcypteridae
      is not supported by phylogenetic trees. Within the Arcypteridae, neither
      Arcypterinae nor Ceracrinae is supported as a monophyletic group. The current
      genus Chorthippus is not a monophyletic group, and should be a polyphyletic
      group. The present results are significantly different from the classification
      scheme of Arcypteridae, which is based on morphology.

PMID- 17498628
TI  - Detection of quantitative trait loci associated with several internal organ
      traits and teat number trait in a pig population.
AB  - Quantitative trait loci (QTL) were detected for 8 internal organ traits, 3
      carcass length traits, and teat number trait in 214 pigs in a resource population
      that included 180 F(2) individuals. A total of 39 microsatellite markers were
      examined on SSC4, SSC6, SSC7, SSC8, and SSC13. The genetic traits included heart
      weight (HW), lung weight (LW), liver and gallbladder weight (LGW), spleen weight
      (SPW), stomach weight (STW), small intestine weight (SIW), large intestine weight
      (LIW), kidney weight (KW), carcass length to the first cervical vertebra (CL1),
      carcass length to the first thoracic vertebra (CL2), rib numbers (RNS), and teat
      numbers (TNS). Results indicated that, 3 highly significant QTL (P <or= 0.01 at
      chromosome-wise level) for HW (at 30 cM on SSC6), RNS (at 115 cM on SSC7), TNS
      (at 110 cM on SSC7), and 6 significant QTL (P <or= 0.05 at chromosome-wise level)
      for LW (at 119 cM on SSC13), LGW (at 94 cM on SSC6), SPW (at 106 cM on SSC8), SIW
      (0 cM on SSC4), LIW (170 cM on SSC 4), and TNS (at 95 cM on SSC6) were detected.
      The phenotypic variances for which these QTL were accounted ranged from 0.04 % to
      14.06 %. Most of these QTL had not been previously reported.

PMID- 17498629
TI  - Structure of the bovine ACAD8 gene and the association of its polymorphism with
      the production traits.
AB  - Acyl-coenzyme A dehydrogenases (ACAD) are a family of nuclear-coded,
      mitochondrial flavoenzymes that catalyze the alpha, and beta-dehydrogenation of
      fatty acids. The eighth member of this family, ACAD8 catalyzes the valine
      catabolism. In this study, the bovine ACAD8 full-length mRNA and genomic DNA
      sequence were obtained and its gene structure was determined through alignment of
      the genomic DNA sequence to the mRNA sequence. The mRNA sequence consisted of a
      1,251 bp open reading frame (ORF) flanked by a 37 bp 5'-untranslated region (UTR)
      and a 444 bp 3'-UTR; and its full-length genomic DNA sequence was 13,814 bp in
      length and included 11 exons and 10 introns. One A-G single nucleotide
      polymorphism (SNP) was revealed at nucleotide 13,408 (GenBank accession No.
      DQ435445) in the bovine ACAD8 gene by sequencing the polymerase chain reaction
      (PCR) products of 6 randomly selected individuals from the sample population.
      Different genotypes were determined by restriction fragment length polymorphism
      (RFLP). The association analysis of this SNP in bovine ACAD8 with production
      traits in 178 unrelated steers from 5 breeds showed that it had a significant
      effect on the daily gain and the beef tenderness (P < 0.05). Cattle with the G
      allele grew more rapidly and the beef they produced was more tender than those
      with the A allele. Thus, this SNP of the bovine ACAD8 gene can be used as an
      indicator to improve the growth rate and the beef tenderness.

PMID- 17498630
TI  - Comparative microsatellite analysis of grass carp genomes of two gynogenetic
      groups and the Xiangjiang River group.
AB  - The genomes of three groups of grass carp, namely the Xiangjiang River grass carp
      group (Xiangjiang group), a one-generation artificially induced meio-gynogenetic
      grass carp group (meio-gynogenetic-1 group), and a two-generation artificially
      induced meio-gynogenetic grass carp group (meio-gynogenetic-2 group), were
      comparatively analyzed with microsatellite markers. Genetic polymorphism had been
      observed in the Xiangjiang group and most of the examined loci had more than two
      alleles. But the degree of genetic diversity was not very high. Although all the
      examined genetic loci in the analyzed individuals were in homozygous state, the
      genotypes of different individuals of the group were not identical in the meio
      gynogenetic-1 group. In the meio-gynogenetic-2 group, not only the examined
      genetic loci of each individual were homozygous but also the genotypes of all the
      analyzed individuals of the group were the same. These results suggested that the
      examined meio-gynogenetic-2 group is a homozygous group and homozygous clone
      could be produced by continuous artificial induction of gynogenesis for two
      generations. It was found that the polymorphism existed not only at the allele
      level but also at the locus level; many alleles of the microsatellite loci and
      some of the microsatellite loci had been lost during the process of artificial
      gynogenesis. Therefore, both protection of the diversity of natural grass carp
      resource and selection of homozygous traits with desired economic genotypes are
      very important aspects for grass carp breeding.

PMID- 17498631
TI  - Physiological character and gene mapping in a new green- revertible albino mutant
      in rice.
AB  - A green-revertible albino mutant-Qiufeng M was found from the japonica rice
      (Oryza sativa L. ssp. japonica) Qiufeng in the field. The first three leaves of
      the mutant were albino with some green. The leaf color became pale green since
      the fourth leaf and the glume had the same phenomenon as the first three leaves.
      The measuring data of the pigment content confirmed the visually observed
      results. It truly had a remarkable changing process in the leaf color in Qiufeng
      M. Comparison of the main agronomic characters between Qiufeng and Qiufeng M
      indicated that the neck length and grain weight showed significant difference at
      the 1% level, and other characters were not different. Genetic analysis showed
      that the green-revertible albino trait was controlled by a single recessive
      nucleic gene. Using 209 recessive mutant individuals in the F(2) population
      derived from the cross Pei'ai 64S x Qiufeng M, a gene, tentatively named
      gra((t)), was located between the SSR markers of RM475 and RM2-22 on the long arm
      of chromosome 2. The genetic distance were 17.3 cM and 2.9 cM respectively.

PMID- 17498632
TI  - Increased endogenous methyl jasmonate altered leaf and root development in
      transgenic soybean plants.
AB  - Methyl jasmonate (MeJA) is a plant-signaling molecule that regulates plant
      morphogenesis and expression of plant defense genes. To determine the role of the
      endogenous MeJA levels in the development of plants, transgenic soybean [Glycine
      max (L.) Merrill] plants harboring NTR1 gene encoding for jasmonic acid carboxyl
      methyltransferase (JMT) were produced. The activation of NTR1 gene expression
      resulted in the production of MeJA. Overexpression of the NTR1 cDNA under the
      regulation of cauliflower mosaic virus (CaMV) 35S promoter in the transgenic
      soybean plants was confirmed using Northern blot analysis. The significant
      differences in leaf and root growth patterns were observed between the transgenic
      plants and the wild-type plants. The leaves of the transgenic plants were
      slightly elongated in length but dramatically narrowed in width compared with the
      nontransformed wild-type plants. In addition, elongation of primary root was
      inhibited in the overexpressed transgenic soybean plantlets, whereas the
      development of lateral root was stimulated relative to the nontransformed plants.
      The leaves of the transgenic plants showed 2-2.5-fold higher levels of MeJA than
      the control plants. These results indicated that the increased endogenous levels
      of MeJA is involved in regulation of morphogenesis in soybean plants.

PMID- 17498633
TI  - Molecular characterization of four ADF genes differentially expressed in cotton.
AB  - Actin depolymerizing factor (ADF), highly conserved in all eukaryotic cells, is a
      low molecular mass of actin-binding protein, which plays a key role in modulating
      the polymerizing and depolymerizing of the actin filaments. Four cDNAs
      (designated GhADF2, GhADF3, GhADF4, and GhADF5, respectively) encoding ADF
      proteins were isolated from cotton (Gossypium hirsutum) fiber cDNA library.
      GhADF2 cDNA is 705 bp in length and deduces a protein with 139 amino acids.
      GhADF3 cDNA is 819 bp in length and encodes a protein of 139 amino acids. GhADF4
      cDNA is 804 bp in length and deduces a protein with 143 amino acids. GhADF5 cDNA
      is 644 bp in length and encodes a protein of 141 amino acids. The molecular
      evolutionary relationship of these genes was analyzed by means of bioinformatics.
      GhADF2 is closely related to GhADF3 (99% identity) and PetADF2 (89% identity).
      GhADF4 is closely related to AtADF6 (78% identity), and GhADF5 is closely related
      to AtADF5 (83% identity). These results demonstrated that the plant ADF genes are
      highly conserved in structure. RT-PCR analysis showed that GhADF2 is
      predominantly expressed in fiber, whereas, GhADF5 is mainly expressed in
      cotyledons. On the other hand, it seems that GhADF3 and GhADF4 have no tissue
      specificity. Expression levels of different ADF genes may vary considerably in
      the same cell type, suggesting that they might be involved in regulating tissue
      development of cotton and the each ADF isoform may diverge to form the functional
      difference from the other ADFs during evolution.

PMID- 17498634
TI  - Isolation and characterization of CMO gene promoter from halophyte Suaeda
      liaotungensis K.
AB  - The 5'-flanking proximal region of stress-induced gene encoding choline
      monooxygenase (CMO) was isolated by Adaptor-PCR and TAIL-PCR from halophyte
      Suaeda liaotungensis K. A total of 2,204 bp DNA sequence was obtained. The
      transcription start site, which is located at 128 bp upstream to the start ATG,
      was predicted by the TSSP-TCM program. The functional elements were analysed by
      PLACE program. The obtained SlCMO gene promoter contains the basic elements: TATA
      box, CAAT-box, and stress-induced elements, for example, salt responsive element
      (GAAAAA), cold responsive elements (CANNTG), ABA (Abscisic Acid) responsive
      elements (NAACAA), water stress element (CGGTTG), and WUN responsive elements
      (GTTAGGTTC). Isolation and analysis of the promoter of the CMO gene from S.
      liaotungensis lays a foundation for characterising the stress-induced promoter
      elements, studying the relationship between the structure and function of the
      promoter, and investigating the molecular mechanism of CMO gene regulation.

PMID- 17498635
TI  - The factors shaping synonymous codon usage in the genome of Burkholderia mallei.
AB  - Burkholderia mallei is regarded as a potential biological weapon by the Centers
      for Disease Control and Prevention. In this study, the main factors shaping codon
      usage in the genome of B. mallei ATCC 23344 were firstly reported. The results
      showed that the primary trend in codon usage variation in the B. mallei is due to
      translational selection; while compositional mutation bias is relatively the
      weaker influence and the hydrophobicity of each protein and gene length are only
      the minor influences. At the same time, 21 codons defined firstly as 'optimal
      codons' might provide more useful information for the expression of target genes
      and development of a vaccine to prevent glanders.

PMID- 17498636
TI  - An entropy-based index for fine-scale mapping of QTL.
AB  - By comparing the entropy and conditional entropy in a marker, an entropy-based
      index for fine-scale linkage-disequilibrium gene mapping is presented using high
      density marker maps in extreme samples for quantitative trait. The entropy-based
      index is the function of LD between the marker and the trait locus and does not
      depend on marker allele frequencies across the loci. It is parallel to Hardy
      Weinberg disequilibrium (HWD) measure for QTL fine mapping, but its power of fine
      mapping QTL is higher than that of HWD measure. Through simulations, the fine
      mapping performance of this entropy-based index is investigated extensively under
      various genetic parameters. The results show that the indices presented here are
      both robust and powerful.

PMID- 17498637
TI  - Molecular characterization of human isolates of Giardia duodenalis from Ethiopia.
AB  - Giardia duodenalis, a flagellated protozoan, represents a common cause of
      gastroenteritis in Ethiopia, however very little information is available on the
      epidemiology and transmission routes of this pathogen, and a genetic
      characterization of the parasite has never been attempted in this country. The
      aim of this study was the genetic analysis of human isolates of G. duodenalis
      collected in different localities across the country, both from urban and rural
      areas. A fragment of the beta-giardin gene was amplified by nested PCR and
      analyzed by restriction and sequence analyses. Of the 59 isolates examined, 31
      (52%) were typed as assemblage A and 13 (22%) as assemblage B. A strong
      correlation between the presence of symptoms and infection with assemblage B was
      observed. The remaining 15 (25%) isolates were typed as mixed infections by PCR
      RFLP, specifically, A+F (in seven isolates) and A+B (in eight isolates).
      Sequencing of the A+F products confirmed the presence of assemblage F in three
      isolates, whereas the remaining four were identified as assemblage A. The
      detection of assemblage F, a cat-specific assemblage that to date has not been
      associated with human infections, was not able to be confirmed by the analysis of
      two commonly used markers (small subunit ribosomal RNA and triosephosphate
      isomerase). The analysis of the one isolate that was successfully amplified with
      the glutamate dehydrogenase primers unambiguously identified it as G. duodenalis,
      yet it was distinct from the established A and F sequences; thus the exact
      genetic identity of these isolates remains unclear.

PMID- 17498638
TI  - Evaluation of the effect of oxamniquine, praziquantel and a combination of both
      drugs on the intramolluscan phase of Schistosoma mansoni.
AB  - The activity of oxamniquine (OXA), praziquantel (PZQ), and a combination of both
      drugs was evaluated at the intramolluscan phase of Schistosoma mansoni.
      Biomphalaria glabrata snails infected with S. mansoni were treated with 500 mg/kg
      OXA, 1000 mg/kg PZQ or with 250 mg/kg OXA and 500 mg/kg PZQ, in association, at
      the pre-patent and patent phases of infection. The results showed that either
      treatments with OXA or PZQ, alone, at the pre-patent period, delayed the
      parasite's development, increasing the pre-patent period by approximately 10
      days. At the same pre-patent period, treatment with a combination of OXA/PZQ
      delayed the parasite's development even more, extending the pre-patent period up
      to 56 days. At the patent period, treatment with OXA and PZQ, alone, interrupted
      cercarial shedding. When the snails were treated with 1000 mg/kg PZQ, the
      cercarial production was re-established 15 days after treatment, but in lower
      numbers than those obtained before treatment, whereas the snails treated with 500
      mg/kg OXA were able to shed cercariae in similar quantities to those observed
      before treatment. The association 250 mg/kg OXA+500 mg/kg PZQ, at the patent
      period, not only discontinued cercarial shedding, but also led to the "cure" of
      the snails, showing a synergistic effect of this combination of drugs. These
      results suggest that this model will be useful for selection of resistant
      parasites, as well as for screening new antischistosomal drugs.

PMID- 17498639
TI  - Horseradish peroxidase embedded in polyacrylamide nanoparticles enables optical
      detection of reactive oxygen species.
AB  - We have synthesized and characterized new nanometer-sized polyacrylamide
      particles containing horseradish peroxidase and fluorescent dyes. Proteins and
      dyes are encapsulated by radical polymerization in inverse microemulsion. The
      activity of the encapsulated enzyme has been examined and it maintains its
      ability to catalyze the oxidation of guaiacol with hydrogen peroxide as the
      electron acceptor, although at a slightly lower rate compared to that of the free
      enzyme in solution. The embedded enzyme is also capable of catalyzing the
      peroxidase-oxidase reaction. However, the rate is decreased by a factor of 2-3
      compared to that of the free enzyme. The reduced rate is probably due to
      limitation of diffusion of substrates and products into and out of the particles.
      The catalytic activity of horseradish peroxidase in the polyacrylamide matrix
      demonstrates that the particles have pores which are large enough for substrates
      to enter and products to leave the polymer matrix containing the enzyme. The
      polymer matrix protects the embedded enzyme from proteolytic digestion, which is
      demonstrated by treating the particles with a mixture of the two proteases
      trypsin and proteinase K. The particles allow for quantification of hydrogen
      peroxide and other reactive oxygen species in microenvironments, and we propose
      that the particles may find use as nanosensors for use in, e.g., living cells.

PMID- 17498640
TI  - Detection of single nucleotide polymorphisms in hepatitis B virus precore/basal
      core promoter region by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry.

PMID- 17498641
TI  - An observation tool to study air traffic control and flightdeck collaboration.
AB  - The complex systems of the flightdeck (FD) and the Air Traffic Control Centre
      (ATC) are characterised by numerous concurrently operating and interacting
      communication channels between people and between people and machines/computer
      systems. This paper describes work in support of investigating the impact of
      changes to technologies and responsibilities within this system with respect to
      human factors. It focuses primarily on the introduction of datalink (text-based
      communication rather than traditional radio communication) and the move towards
      freeflight (pilot-mediated air traffic control). Air traffic management
      investigations have outlined these specific changes as strategies to enable
      further increases in the volume of air traffic. A systems approach was taken and
      field studies were conducted. Small numbers of domain experts such as air traffic
      controllers (ATCOs) were involved in the field-based observations of how people
      interact with systems and each other. This paper summarises the overall research
      approach taken and then specifically reports on the field-based observations
      including the justification, development, and findings of the observation tool
      used. The observation tool examined information propagation through the air
      traffic control-flightdeck (ATC-FD) system, and resulted in models of possible
      information trajectories through the system.

PMID- 17498642
TI  - Designing interactive consumer products: utility of paper prototypes and
      effectiveness of enhanced control labelling.
AB  - The studies reported here examined differences in user behaviour when presented
      with a low-fidelity paper prototype compared to fully operational product, and
      evaluated the effectiveness of different types of enhanced labelling of controls.
      In the first study with a paper prototype, 30 users of high-pressure washers were
      asked to choose the settings of the temperature control for different cleaning
      objects, comparing standard with information-enriched control labelling. In the
      second study, 34 users operated a real high-pressure washer with different forms
      of control labelling. The results of both studies provided evidence for some
      benefits of an information-enriched control labelling over traditional
      temperature-centred controls labelling. Furthermore, a comparative analysis of
      the data of the two studies suggested that low-fidelity paper prototypes may have
      to be used with caution. Therefore, designers need to be aware that the
      behavioural effects induced by different design modifications may be
      overestimated when using paper prototypes. The implications of the findings are
      discussed within the framework of an enlarged concept of fidelity.

PMID- 17498643
TI  - Signal transducer and activator of transcription 3 and sphingomyelin metabolism
      in intranuclear complex during cell proliferation.
AB  - An "intranuclear complex" characterized by the presence of a new synthesised
      double-strand RNA stabilized by sphingomyelin and cholesterol has been recently
      isolated from hepatocyte nuclei. In the present research the existence of STAT3
      in the intranuclear complex and its behaviour in relation to cyclin D and
      sphingomyelin metabolism during liver regeneration were studied with the aim to
      see if the sphingomyelinase could have a role in cell proliferation. Our data
      demonstrate that the transcription factor is present in the intranuclear complex
      either as unphosphorylated or phosphorylated monomeric form. After partial
      hepatectomy, unphosphorylated STAT3 is very low during G1/S transition of the
      cell cycle and it increases in correspondence of the of S-phase of the cell cycle
      when cyclin D1 is reduced. The phosphorylated form increases at the beginning of
      the S-phase when the neutral sphingomyelinase activity is stimulated with
      consequent enrichment of ceramide pool. In order to see if the two phenomena
      could be correlated, the intranuclear complex extracted from normal liver was
      treated with exogenous sphingomyelinase or ceramide and STAT3 was evaluated. The
      results show an increase of the phosphorylated transcription factor as happens in
      liver regeneration, suggesting that sphingomyelinase present in the intranuclear
      complex is responsible for the STAT3 activation during cell proliferation.

PMID- 17498644
TI  - Expression, characterization, and gene knockdown of zebrafish doublecortin-like
      protein kinase.
AB  - Doublecortin-like protein kinase (DCLK) is a protein Ser/Thr kinase expressed in
      brain and believed to play crucial roles in neuronal development. To investigate
      the biological significance of DCLK, we isolated cDNA clones for zebrafish DCLK
      (zDCLK) and found that there were five splice variants of the kinase. In this
      study, the catalytic properties of a major isoform of zDCLK, which we designated
      as zDCLK1, and of an N-terminal truncated mutant retaining the kinase domain were
      examined by expressing them in Escherichia coli. Mutational analysis of
      recombinant zDCLK suggested that the kinase was activated not only by
      phosphorylation at Thr-576 in the activation loop but also by autophosphorylation
      at the other site(s) in the catalytic domain. zDCLK significantly phosphorylated
      protein substrates such as myelin basic protein, histones, and synapsin I.
      Subcellular localization of zDCLK and its N-terminal deletion mutant implicated
      that microtubule-association of zDCLK is mediated through N-terminal doublecortin
      like domain of this enzyme. Western blotting analysis and whole mount in situ
      hybridization revealed that zDCLK was highly expressed in brain and eyes after 24
      h post fertilization. Gene knockdown of zDCLK using morpholino-based antisense
      oligonucleotides induced significant increase of apoptotic cells in the central
      nervous systems and resulted in the increase of the morphologically abnormal
      embryos in a dose-dependent manner. These results suggest that zDCLK may play
      crucial roles in the central nervous systems during the early stage of
      embryogenesis.

PMID- 17498645
TI  - Essential amino acid residues in the central transmembrane domains and loops for
      energy coupling of Streptomyces coelicolor A3(2) H+-pyrophosphatase.
AB  - The H+-translocating inorganic pyrophosphatase is a proton pump that hydrolyzes
      inorganic pyrophosphate. It consists of a single polypeptide with 14-17
      transmembrane domains, and is found in a range of organisms. We focused on the
      second quarter region of Streptomyces coelicolor A3(2) H+-pyrophosphatase, which
      contains long conserved cytoplasmic loops. We prepared a library of 1536 mutants
      that were assayed for pyrophosphate hydrolysis and proton translocation. Mutant
      enzymes with low substrate hydrolysis and proton-pump activities were selected
      and their DNAs sequenced. Of these, 34 were single-residue substitution mutants.
      We generated 29 site-directed mutant enzymes and assayed their activity. The
      mutation of 10 residues in the fifth transmembrane domain resulted in low
      coupling efficiencies, and a mutation of Gly198 showed neither hydrolysis nor
      pumping activity. Four residues in cytoplasmic loop e were essential for
      substrate hydrolysis and efficient H+ translocation. Pro189, Asp281, and Val351
      in the periplasmic loops were critical for enzyme function. Mutation of Ala357 in
      periplasmic loop h caused a selective reduction of proton-pump activity. These
      low-efficiency mutants reflect dysfunction of the energy-conversion and/or proton
      translocation activities of H+-pyrophosphatase. Four critical residues were also
      found in transmembrane domain 6, three in transmembrane domain 7, and five in
      transmembrane domains 8 and 9. These results suggest that transmembrane domain 5
      is involved in enzyme function, and that energy coupling is affected by several
      residues in the transmembrane domains, as well as in the cytoplasmic and
      periplasmic loops. H+-pyrophosphatase activity might involve dynamic linkage
      between the hydrophilic and transmembrane domains.

PMID- 17498646
TI  - Diverse effects of phospholipids on lipoprotein sorting and ATP hydrolysis by the
      ABC transporter LolCDE complex.
AB  - The LolCDE complex of Escherichia coli releases outer membrane-specific
      lipoproteins from the inner membrane. Lipoproteins with Asp at +2 remain in the
      inner membrane since this residue functions as a LolCDE avoidance signal
      depending on phosphatidylethanolamine. We examined the effects of other
      phospholipids on lipoprotein sorting in proteoliposomes reconstituted with LolCDE
      and various synthetic phospholipids. The lipoprotein release and ATP hydrolysis
      were both low at 2 mM Mg(2+) but very high at 10 mM Mg(2+) in proteoliposomes
      containing cardiolipin alone. However, the Lol avoidance function was abolished
      at 10 mM Mg(2+), and the release of lipoproteins with Asp at +2 was as efficient
      as that of outer membrane-specific lipoproteins. The addition of
      phosphatidylethanolamine to cardiolipin stimulated the ATP hydrolysis and
      increased the Lol avoidance function of Asp at +2 at 2 mM Mg(2+). The addition of
      phosphatidylglycerol to cardiolipin nearly completely inhibited the release of
      lipoproteins with Asp at +2 even at 10 mM Mg(2+), while that of outer membrane
      specific lipoproteins was not. Taken together, these results indicate that three
      major phospholipids of E. coli differently affect lipoprotein sorting and the
      activity of LolCDE.

PMID- 17498647
TI  - Regulation of intestinal hPepT1 (SLC15A1) activity by phosphodiesterase
      inhibitors is via inhibition of NHE3 (SLC9A3).
AB  - The H(+)-coupled transporter hPepT1 (SLC15A1) mediates the transport of
      di/tripeptides and many orally-active drugs across the brush-border membrane of
      the small intestinal epithelium. Incubation of Caco-2 cell monolayers (15 min)
      with the dietary phosphodiesterase inhibitors caffeine and theophylline inhibited
      Gly-Sar uptake across the apical membrane. Pentoxifylline, a phosphodiesterase
      inhibitor given orally to treat intermittent claudication, also decreased Gly-Sar
      uptake through a reduction in capacity (V(max)) without any effect on affinity
      (K(m)). The reduction in dipeptide transport was dependent upon both
      extracellular Na(+) and apical pH but was not observed in the presence of the
      selective Na(+)/H(+) exchanger NHE3 (SLC9A3) inhibitor S1611. Measurement of
      intracellular pH confirmed that caffeine was not directly inhibiting hPepT1 but
      rather having an indirect effect through inhibition of NHE3 activity. NHE3
      maintains the H(+)-electrochemical gradient which, in turn, acts as the driving
      force for H(+)-coupled solute transport. Uptake of beta-alanine, a substrate for
      the H(+)-coupled amino acid transporter hPAT1 (SLC36A1), was also inhibited by
      caffeine. The regulation of NHE3 by non-nutrient components of diet or orally
      delivered drugs may alter the function of any solute carrier dependent upon the
      H(+)-electrochemical gradient and may, therefore, be a site for both nutrient
      drug and drug-drug interactions in the small intestine.

PMID- 17498649
TI  - RNA polymerase II determines the area of nucleosome loss in transcribed gene
      loci.
AB  - Upon transcriptional activation, nucleosomes are removed from not only promoters
      but also coding regions of highly transcribed genes. However, the mechanisms and
      factors determining the borders of nucleosome-depleted loci are not known. Here,
      we identify elongating RNA polymerase II as a major factor for defining the
      region of nucleosome removal in transcribed genes. We also show that upon shut
      down of transcription, newly synthesised histones are used for formation of
      nucleosomes in the coding region of recently transcribed gene locus.

PMID- 17498648
TI  - Loss of LRRK2/PARK8 induces degeneration of dopaminergic neurons in Drosophila.
AB  - Mutations in LRRK2/PARK8 are linked to autosomal dominant forms of Parkinson's
      disease, but the pathogenic mechanism of LRRK2-associated Parkinson's disease is
      not fully understood. Moreover, in vivo functions of LRRK2 have not been
      addressed so far. Thus, we generated and characterized transgenic animals and
      loss-of-function mutants for LRRK, a sole Drosophila orthologue of human LRRK2.
      While transgenic expression of pathogenic mutant and wild type LRRK did not show
      any significant defects, LRRK loss-of-function mutants exhibited severely
      impaired locomotive activity. Moreover, dopaminergic neurons in LRRK mutants
      showed a severe reduction in tyrosine hydroxylase immunostaining and shrunken
      morphology, implicating their degeneration in the mutants. Collectively, our
      findings unprecedentedly show in vivo that LRRK2 is critical for the integrity of
      dopaminergic neurons and intact locomotive activity in Drosophila.

PMID- 17498650
TI  - Restrictase free generation of targeting vectors for disruption of complex mouse
      genes.
AB  - Molecular cloning of targeting vectors (TgVs) is a prerequisite procedure for
      gene disruption in embryonic stem cells. In cases where target genes display
      complex features (e.g., gene overlap, alternative exon usage), TgVs must mediate
      deletions with very high precision to prevent unwanted effects. This is often
      difficult to achieve by procedures using restriction endonucleases and DNA
      ligases. Therefore, to prepare TgVs for inactivation of two complex genes of
      immunological interest: PTPRF and NWC, we employed an alternative method, which
      involves engineering bacterial artificial chromosomes (BACs) by inducible,
      plasmid encoded "Red/ET recombinase" expression system. Here, we report rapid and
      efficient construction of PTPRF and NWC TgVs without using restriction
      endonucleases.

PMID- 17498651
TI  - Activation-induced changes in alternate splice acceptor site usage.
AB  - An AGCAG motif at 3' splice acceptor sites in a diverse set of genes creates
      alternate in-frame splice acceptor sites that produce alternate protein isoforms
      differing by a single amino acid. Among a group of over 12,000 EST-verified
      splice acceptor sites, only 74 genes were identified that contained the AGCAG
      motif, comprising about 0.7% of the total. In some cases the location of the
      single amino acid insertion occurs in a region with the potential to affect
      protein function. Analysis of cDNA from five different human genes of immunologic
      interest that contain the AGCAG motif, CD3zeta, CD79B, PLCgamma1, CD19, and CD32B
      (FcgammaRIIB), confirms that each gene encodes the two predicted splice variants.
      Variations occur in the splice variant ratio in all five of the genes tested
      during T and B cell activation, suggesting that the ratio is regulated by the
      cellular activation state. These results suggest that activation-induced
      variation in mRNA splicing may represent a mechanism for functional modulation of
      these proteins.

PMID- 17498652
TI  - Development and assessment of whole-genome oligonucleotide microarrays to analyze
      an anaerobic microbial community and its responses to oxidative stress.
AB  - The application of DNA microarray technology to investigate multiple-species
      microbial communities presents great challenges. In this study, we reported the
      design and quality assessment of four whole genome oligonucleotide microarrays
      for two syntroph bacteria, Desulfovibrio vulgaris and Syntrophobacter
      fumaroxidans, and two archaeal methanogens, Methanosarcina barkeri, and
      Methanospirillum hungatei, and their application to analyze global gene
      expression in a four-species microbial community in response to oxidative stress.
      In order to minimize the possibility of cross-hybridization, cross-genome
      comparison was performed to assure all probes unique to each genome so that the
      microarrays could provide species-level resolution. Microarray quality was
      validated by the good reproducibility of experimental measurements of multiple
      biological and analytical replicates. This study showed that S. fumaroxidans and
      M. hungatei responded to the oxidative stress with up-regulation of several genes
      known to be involved in reactive oxygen species (ROS) detoxification, such as
      catalase and rubrerythrin in S. fumaroxidans and thioredoxin and heat shock
      protein Hsp20 in M. hungatei. However, D. vulgaris seemed to be less sensitive to
      the oxidative stress as a member of a four-species community, since no gene
      involved in ROS detoxification was up-regulated. Our work demonstrated the
      successful application of microarrays to a multiple-species microbial community,
      and our preliminary results indicated that this approach could provide novel
      insights on the metabolism within microbial communities.

PMID- 17498653
TI  - Participation of caveolae in beta1 integrin-mediated mechanotransduction.
AB  - We previously reported that caveolin-1 is a key component in a beta1 integrin
      dependent mechanotransduction pathway suggesting that caveolae organelles and
      integrins are functionally linked in their mechanotransduction properties. Here,
      we exposed BAEC monolayers to shear stress then isolated caveolae vesicles form
      the plasma membrane. While little beta1 integrin was detected in caveolae derived
      from cells kept in static culture, shear stress induced beta1 integrin
      transposition to the caveolae. To evaluate the significance of shear-induced
      beta1 integrin localization to caveolae, cells were pretreated with cholesterol
      sequestering compounds or caveolin-1 siRNA to disrupt caveolae structural
      domains. Cholesterol depletion attenuated integrin-dependent caveolin-1
      phosphorylation, Src activation and Csk association with beta1 integrin.
      Reduction of both caveolin-1 protein and membrane cholesterol inhibited
      downstream shear-induced, integrin-dependent phosphorylation of myosin light
      chain. Taken together with our previous findings, the data supports the concept
      that beta1 integrin-mediated mechanotransduction is mediated by caveolae domains.

PMID- 17498654
TI  - SUMO modification modulates the transrepression activity of PLZF.
AB  - Small ubiquitin-like modifier (SUMO) modification has recently been shown to
      associate with transcriptional regulation and nuclear body formation. Here, we
      show that transcription factor PLZF can be SUMO modified at lysine residue 242,
      387 and 396. Converting these three SUMO acceptor Lys to Arg 3KR does not
      significantly affect PLZF nuclear body formation, which is distinct from the
      scenario of PML sumoylation in PML nuclear body formation. Furthermore, PLZF-3KR
      markedly reduced the transcriptional repression activity, correlating with a loss
      of PLZF-mediated growth suppression. These results reveal an important role of
      SUMO modification in PLZF-mediated transcriptional repression.

PMID- 17498655
TI  - Hydrogen peroxide can be generated by tau in the presence of Cu(II).
AB  - Alzheimer's disease has been closely related with oxidative stress, which might
      be responsible for the dysfunction or death of neuronal cells that contributes to
      disease pathogenesis. Impaired copper homeostasis makes contribution to the
      oxidative stress and consequently to several neurodegenerative conditions.
      Inappropriate binding of Cu(II) to cellular proteins are currently being explored
      as sources of pathological oxidative stress in several neurodegenerative
      disorders. Here we report that a fragment of tau protein possesses copper
      reduction activity and initiates the copper-mediated generation of hydrogen
      peroxide. The tau peptide was found to be oxidized to form disulfide bond-linked
      dimer. The hydrogen peroxide generated was quantified by TCEP/DTNB (tris(2
      carboxyethyl) phosphine hydrochloride/5,5'-dithio-bis(2-nitrobenzoic acid). Since
      the copper reduction capacity and the generation of hydrogen peroxide were
      believe to be a major toxicological pathway of Abeta peptide, the functional
      similarity shared by tau and Abeta implies a new perspective of tau pathology.

PMID- 17498656
TI  - Deficiency in the response to DNA double-strand breaks in mouse early
      preimplantation embryos.
AB  - DNA double-strand breaks (DSBs) are caused by various environmental stresses,
      such as ionizing radiation and DNA-damaging agents. When DSBs occur, cell cycle
      checkpoint mechanisms function to stop the cell cycle until all DSBs are
      repaired; the phosphorylation of H2AX plays an important role in this process.
      Mouse preimplantation-stage embryos are hypersensitive to ionizing radiation, and
      X-irradiated mouse zygotes are arrested at the G2 phase of the first cell cycle.
      To investigate the mechanisms responding to DNA damage at G2 in mouse
      preimplantation embryos, we examined G2/M checkpoint and DNA repair mechanisms in
      these embryos. Most of the one- and two-cell embryos in which DSBs had been
      induced by gamma-irradiation underwent a delay in cleavage and ceased development
      before the blastocyst stage. In these embryos, phosphorylated H2AX (gamma-H2AX)
      was not detected in the one- or two-cell stages by immunocytochemistry, although
      it was detected after the two-cell stage during preimplantation development.
      These results suggest that the G2/M checkpoint and DNA repair mechanisms have
      insufficient function in one- and two-cell embryos, causing hypersensitivity to
      gamma-irradiation. In addition, phosphorylated ataxia telangiectasia mutated
      protein and DNA protein kinase catalytic subunits, which phosphorylate H2AX, were
      detected in the embryos at one- and two-cell stages, as well as at other
      preimplantation stages, suggesting that the absence of gamma-H2AX in one- and two
      cell embryos depends on some factor(s) other than these kinases.

PMID- 17498657
TI  - Elimination of radiation-induced gamma-H2AX foci in mammalian nucleus can occur
      by histone exchange.
AB  - Double-strand breaks in mammalian DNA lead to rapid phosphorylation of C-terminal
      serines in histone H2AX (gamma-H2AX) and formation of large nuclear gamma-H2AX
      foci. After DNA repair these foci disappear, but molecular mechanism of
      elimination of gamma-H2AX foci remains unclear. H2AX protein can be
      phosphorylated and dephosphorylated in vitro in the absence of chromatin. Here,
      we compared global exchange of GFP-H2AX with kinetics of formation and
      elimination of radiation-induced gamma-H2AX foci. Maximal number of gamma-H2AX
      foci is observed one hour after irradiation, when approximately 20% of GFP-H2AX
      is exchanged suggesting that formation of the foci mostly occurs by in situ H2AX
      phosphorylation. However, slow elimination of gamma-H2AX foci is weakly affected
      by an inhibitor of protein phosphatases calyculin A which is known as an agent
      suppressing dephosphorylation of gamma-H2AX. This indicates that elimination of
      gamma-H2AX foci may be independent of dephosphorylation of H2AX which can occur
      after its removal from the foci by exchange.

PMID- 17498658
TI  - Monomeric A beta and metals reduce their cytotoxicities to each other.
AB  - The present study has examined the effect of metals, such as iron and copper on
      the cytotoxicity of amyloid beta protein 1-40 (Abeta40). First, we showed that
      monomeric Abeta40 has stronger cytotoxicity than various type of aggregated
      Abeta40. Next we showed the addition of metals into the monomeric Abeta40 reduced
      the cytotoxicity of either monomeric Abeta40 or metals (iron and copper) although
      the addition of metals into monomeric Abeta40 resulted in a marked increase of
      aggregated form of Abeta40, which composed of beta-sheeted Abeta40 and Abeta40
      aggregation not characterized by beta-sheet fibrils (coagrated Abeta40). Taken
      together, the metals and monomeric Abeta40 affect on each other and cause the
      reduction of their cell toxicity.

PMID- 17498659
TI  - Solution structure of BRD7 bromodomain and its interaction with acetylated
      peptides from histone H3 and H4.
AB  - BRD7 is an important protein tightly associated with Nasopharyngeal carcinoma
      (NPC). Overexpression of BRD7 inhibits NPC cell growth and cell cycle by
      transcriptionally regulating the cell cycle related genes. BRD7 contains a
      bromodomain that is found in many chromatin-associated proteins and in nearly all
      known nuclear histone acetyltransferases (HATs) and plays an important role in
      chromatin remodeling and transcriptional activation. Here, we report the solution
      structure of BRD7 bromodomain determined by NMR spectroscopy, and its binding
      specificity revealed by NMR titration with several acetylated histone peptides.
      We find that BRD7 bromodomain contains the typical left-handed four-helix bundle
      topology, and can bind with weak affinity to lysine-acetylated peptides derived
      from histone H3 with K9 or K14 acetylated and from histone H4 with K8, K12 or K16
      acetylated. Our results show that BRD7 bromodomain lacks inherent binding
      specificity when binding to histones in vitro.

PMID- 17498660
TI  - SNX1 and SNX2 mediate retrograde transport of Shiga toxin.
AB  - The bacterial toxin Shiga toxin (Stx) is transported retrogradely from early
      endosomes to the Golgi apparatus on its way to the endoplasmic reticulum (ER) and
      the cytosol. In this study we explored the functions of the two phosphoinositide
      binding proteins Sorting nexin 1 (SNX1) and Sorting nexin 2 (SNX2) in endosomal
      sorting of the toxin. When Vero cells were depleted of either SNX1 or SNX2 by
      small interfering RNA (siRNA), Stx transport to the trans-Golgi network (TGN) was
      impaired by > or = 40%, whereas combined depletion of SNX1 and SNX2 gave a total
      inhibition of approximately 80%. Inhibition of PI(3)P formation by wortmannin
      resulted in a similar reduction. Thus, although being partly redundant, both SNX1
      and SNX2 are required for efficient Stx trafficking to the Golgi apparatus.

PMID- 17498661
TI  - Differential expression pattern of UBX family genes in Caenorhabditis elegans.
AB  - UBX (ubiquitin regulatory X)-containing proteins belong to an evolutionary
      conserved protein family and determine the specificity of p97/VCP/Cdc48p function
      by binding as its adaptors. Caenorhabditis elegans was found to possess six UBX
      containing proteins, named UBXN-1 to -6. However, no general or specific function
      of them has been revealed. During the course of understanding not only their
      function but also specified function of p97, we investigated spatial and temporal
      expression patterns of six ubxn genes in this study. Transcript analyses showed
      that the expression pattern of each ubxn gene was different throughout worm's
      development and may show potential developmental dynamics in their function,
      especially ubxn-5 was expressed specifically in the spermatogenic germline,
      suggesting a crucial role in spermatogenesis. In addition, as ubxn-4 expression
      was induced by ER stress, it would function as an ERAD factor in C. elegans. In
      vivo expression analysis by using GFP translational fusion constructs revealed
      that six ubxn genes show distinct expression patterns. These results altogether
      demonstrate that the expression of all six ubxn genes of C. elegans is
      differently regulated.

PMID- 17498662
TI  - Signaling induced by hop/STI-1 depends on endocytosis.
AB  - The co-chaperone hop/STI-1 is a ligand of the cell surface prion protein
      (PrP(C)), and their interaction leads to signaling and biological effects. Among
      these, hop/STI-1 induces proliferation of A172 glioblastoma cells, dependent on
      both PrP(C) and activation of the Erk pathway. We tested whether clathrin
      mediated endocytosis affects signaling induced by hop/STI-1. Both hyperosmolarity
      induced by sucrose and monodansyl-cadaverine blocked Erk activity induced by
      hop/STI-1, without affecting the high basal Akt activity typical of A172. The
      endocytosis inhibitors also affected the sub-cellular distribution of
      phosphorylated Erk, consistent with blockade of the latter's activity. The data
      indicate that signaling induced by hop/STI-1 depends on endocytosis. These
      findings are consistent with a role of sub-cellular trafficking in signal
      transduction following engagement by PrP(C) by ligands such as hop/STI-1, and may
      help help unravel both the functions of the prion protein, as well as possible
      loss-of-function components of prion diseases.

PMID- 17498663
TI  - Reduced response of splenocytes after mitogen-stimulation in the prion protein
      (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration.
AB  - Splenocytes of wild-type (Prnp(+/+)) and prion protein gene-deficient (Prnp(-/-))
      mice were treated with various activation stimuli such as T cell mitogen
      concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA)+ionomycin (Io), or B
      cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP(C)) expression
      was enhanced following ConA stimulation, but not PMA+Io or LPS in Prnp(+/+)
      splenocytes. Rikn Prnp(-/-) splenocytes elicited lower cell proliferations than
      Prnp(+/+) or Zrch I Prnp(-/-) splenocytes after LPS stimulation and showed
      sporadic nerve cells in the cerebral cortex and deeper structure. Around the
      degenerated nerve cells, mild vacuolation in the neuropil was observed. This
      neural alteration correlated well to the suppressed response of B cells in the
      spleen. The finding that discrete lesions within the central nervous systems
      induced marked modulation of immune function probably indicates the existence of
      a delicately balanced neural-endocrine network by PrP(C) and PrPLP/Doppel.

PMID- 17498664
TI  - Cyclin dependent kinase 5 (Cdk5) mediated inhibition of the MAP kinase pathway
      results in CREB down regulation and apoptosis in PC12 cells.
AB  - Cyclin dependent kinase 5 (cdk5) is active mainly in postmitotic cells like
      neurons and regulates important cellular functions by phosphorylating a wide
      variety of targets. Nerve growth factor stimulates the MEK-ERK MAP kinase pathway
      and causes neuronal differentiation and survival. It was reported previously that
      Cdk5 inhibits the MAP kinase pathway by phosphorylating Map kinase kinase-1
      (MEK1) [1]. We have delineated the functional consequence of this cross talk and
      found that the cdk5 mediated inhibition of MEK1 results in apoptosis. We also
      demonstrate that the activity of transcription factor CREB, which is known to
      play pro-survival roles in neuronal cells, is attenuated as a result of this
      cross-talk.

PMID- 17498665
TI  - Leishmania replication protein A-1 binds in vivo single-stranded telomeric DNA.
AB  - Replication protein A (RPA) is a highly conserved heterotrimeric single-stranded
      DNA-binding protein involved in different events of DNA metabolism. In yeast,
      subunits 1 (RPA-1) and 2 (RPA-2) work also as telomerase recruiters and, in
      humans, the complex unfolds G-quartet structures formed by the 3' G-rich
      telomeric strand. In most eukaryotes, RPA-1 and RPA-2 bind DNA using multiple OB
      fold domains. In trypanosomatids, including Leishmania, RPA-1 has a canonical OB
      fold and a truncated RFA-1 structural domain. In Leishmania amazonensis, RPA-1
      alone can form a complex in vitro with the telomeric G-rich strand. In this work,
      we show that LaRPA-1 is a nuclear protein that associates in vivo with Leishmania
      telomeres. We mapped the boundaries of the OB fold DNA-binding domain using
      deletion mutants. Since Leishmania and other trypanosomatids lack homologues of
      known telomere end binding proteins, our results raise questions about the
      function of RPA-1 in parasite telomeres.

PMID- 17498666
TI  - Cisplatin and doxorubicin repress Vascular Endothelial Growth Factor expression
      and differentially down-regulate Hypoxia-inducible Factor I activity in human
      ovarian cancer cells.
AB  - Vascular Endothelial Growth Factor (VEGF) and its transcriptional regulator
      Hypoxia-inducible Factor 1 (HIF-1) play an important role in the process of
      angiogenesis in many types of cancer, including ovarian cancer. We have examined
      whether the DNA-damaging drugs cisplatin and doxorubicin and the microtubule
      inhibitors docetaxel and paclitaxel can affect VEGF expression and HIF-1 activity
      in three human ovarian cancer cell lines. We demonstrate that cisplatin and
      doxorubicin abolish hypoxia-induced VEGF mRNA expression in all cell lines, while
      basal VEGF mRNA expression was also downregulated. Transient transfection with a
      HIF-1-responsive luciferase construct indicated that cisplatin and doxorubicin
      inhibited hypoxic activation of HIF-1. Cisplatin repressed HIF-1alpha protein
      expression in all cell lines. Stimulation of HIF-1alpha protein degradation by
      cisplatin was observed in the only cell line expressing wild-type p53. Cisplatin
      also inhibited the synthesis of HIF-1alpha protein for which p53 was dispensable.
      Interestingly, cisplatin strongly reduced the protein levels of the HIF-1
      coactivators p300 and CREB-binding protein (CBP) under hypoxia in all cell lines.
      Although doxorubicin inhibited hypoxic activation of HIF-1, this drug had no
      significant effect on the expression levels of HIF-1alpha and hypoxic expression
      of p300 and CBP was only weakly reduced. Docetaxel and paclitaxel did neither
      influence VEGF expression nor hypoxia-induced HIF-1 activity. In total, our
      findings indicate that cisplatin and doxorubicin can repress hypoxic induction of
      VEGF expression by inhibiting HIF-1 through different mechanisms. This knowledge
      may be useful for future treatment schedules including agents that target the HIF
      1 signalling pathway.

PMID- 17498667
TI  - HDAC inhibitors: clinical update and mechanism-based potential.
AB  - Recently, the role of transcriptional repression through epigenetic modulation in
      carcinogenesis has been clinically validated with several inhibitors of histone
      deacetylases and DNA methyltransferases. It has long been recognized that
      epigenetic alterations of tumor suppressor genes was one of the contributing
      factors in carcinogenesis. Inhibitors of histone deacetylase (HDAC) de-repress
      genes that subsequently result in growth inhibition, differentiation and
      apoptosis of cancer cells. Vorinostat (SAHA), romidepsin (depsipeptide, FK-228),
      belinostat (PXD101) and LAQ824/LBH589 have demonstrated therapeutic benefit as
      monotherapy in cutaneous T-cell lymphoma (CTCL) and have also demonstrated some
      therapeutic benefit in other malignancies. The approval of the HDAC inhibitor
      vorinostat (Zolinzatrade mark) was based on the inherent sensitivity of this type
      of lymphoma to alterations in acetylation patterns that resulted in the induction
      of repressed apoptotic pathways. However, the full potential of these inhibitors
      (epigenetic modulators) is still on the horizon, as the true breadth of their
      utility as anti-cancer agents will be determined by the careful analysis of gene
      expression changes generated by these inhibitors and then combined with
      conventional chemotherapy to synergistically improve response and toxicity for an
      overall enhanced therapeutic benefit to the patient. The question that must be
      considered is whether the current HDACIs are being utilized to their fullest
      potential in clinical trials based on their mechanism-based alterations in
      disease processes.

PMID- 17498668
TI  - Artemisinin effectiveness in erythrocytes is reduced by heme and heme-containing
      proteins.
AB  - Artemisinin loses its antimalarial activity on prolonged exposure to
      erythrocytes, especially alpha-thalassemic erythrocytes. In this report, we show
      that the major artemisinin-inactivating factor in cytosol of normal erythrocytes
      was heat-labile but a heat-stable factor from alpha-thalassemic cells also played
      a significant role in reducing artemisinin effectiveness, which was shown to be
      heme released from hemoglobin (Hb). Studies of fractionated lysate from
      genetically normal erythrocytes revealed that the protein fraction with molecular
      weight greater than 100 kDa was capable of reducing artemisinin effectiveness
      more readily than lower molecular weight fraction. Catalase and Hb A, but not
      selenoprotein glutathione peroxidase, were capable of reducing artemisinin
      effectiveness. Hemin (ferriprotoporphyrin IX) also reduced artemisinin
      effectiveness in a concentration- and time-dependent manner. It is concluded that
      heme and heme-containing proteins in erythrocyte are largely responsible for
      reducing artemisinin effectiveness and may contribute to resistance of Plasmodium
      falciparum infecting alpha-thalassemic erythrocytes observed in vitro.

PMID- 17498669
TI  - Involvement of Y(5) receptors in neuropeptide Y agonist-induced analgesic-like
      effect in the rat hot plate test.
AB  - Neuropeptide Y (NPY) induces analgesic-like effects after central administration
      across diverse pain models in rodents. In spinal pain models, previous studies
      indicate a prominent role for Y(1) receptors at mediating this effect of NPY. In
      supraspinal pain models like the hot plate test, the NPY receptors involved have
      not been thoroughly explored. By intracerebroventricular (i.c.v.) administration
      of selective NPY receptor ligands, the possible involvement of Y(5) receptors in
      analgesic-like mechanisms was investigated using the hot plate test in rats. Both
      NPY and selective Y(5) agonists induced analgesic-like effects as revealed by
      prolonged hot plate latencies. Further consistent with a role for Y(5) receptors,
      pretreatment with a selective Y(5) receptor antagonist blocked the Y(5) agonist
      induced analgesic-like effect. The present study indicates involvement of Y(5)
      receptors probably at the supraspinal level in mediation of NPY agonist-induced
      analgesic-like effects in the hot plate test.

PMID- 17498670
TI  - Hierarchical error processing: different errors, different systems.
AB  - Error processing during motor control involves the evaluation of "high-level"
      errors (i.e., failures to meet a system goal) by a frontal system involving
      anterior cingulate cortex and the evaluation of "low-level" errors (i.e.,
      discrepancies between actual and desired motor commands) by a posterior system
      involving posterior parietal cortex. We have recently demonstrated that high
      level errors committed within the context of a continuous tracking task elicited
      an error-related negativity (ERN) -- a component of the event-related brain
      potential (ERP) generated within medial-frontal cortex that is sensitive to error
      commission. The purpose of the present study was to demonstrate that low-level
      motor errors do not elicit an ERN, but may instead evoke other ERP components
      associated with visual processing and online motor control. Participants
      performed a computer aiming task in which they manipulated a joystick to move a
      cursor from a start to a target position. On a random subset of trials the target
      jumped to a new position at movement onset, requiring the participants to modify
      their current motor command. Further, on one half of these "target perturbation"
      trials the cursor did not respond to corrective movements of the joystick.
      Consistent with our previous findings, we found that the uncorrectable errors
      elicited an ERN. We also found that the target perturbations on both correctable
      and uncorrectable trials did not elicit an ERN, but rather evoked two other ERP
      components, the N100 and P300. These results suggest that medial-frontal cortex
      is insensitive to low-level motor errors, and are in line with a recent theory
      that holds that the P300 reflects stimulus-response optimization by the impact of
      locus coeruleus activity on posterior cortex.

PMID- 17498671
TI  - Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal
      survival in hippocampal cultures.
AB  - The significance of multiple growth factors acting on individual neurons in the
      central nervous system is presently unclear. Cultured hippocampal neurons were
      used in the present study to compare the neurotrophic actions of fibroblast
      growth factor-2 (FGF-2) with the better characterized growth factors, insulin
      like growth factor (IGF)-1 and brain-derived neurotrophic factor (BDNF).
      Additionally, cultures were utilized to identify possible interactions between
      FGF-2 and the other growth factors. Activation of the ERK and Akt pro-survival
      pathways, as well as neuronal survival itself, were studied. The maximal
      magnitude of Akt activation stimulated by FGF-2 was found to be similar to that
      stimulated by IGF-1 and BDNF. In contrast, IGF-1 was less effective at inducing
      ERK activation than were BDNF and FGF-2. All three agents were found to promote
      survival of neurons cultured under serum-free, low-insulin conditions, with FGF-2
      surprisingly being significantly more effective than the other two peptides. Co
      treatment with maximal concentrations of either IGF-1 or BDNF enhanced FGF-2
      stimulated Akt and ERK activation. However, no enhancement of survival beyond
      that stimulated by FGF-2 was observed with co-treatment. These findings suggest
      that FGF-2 may play an important role in promoting the survival of hippocampal
      neurons. Additionally, an interesting dissociation was identified between the
      positive interaction of FGF-2 with both IGF-1 and BDNF in activating Akt and ERK,
      and the lack of enhancement of FGF-2-induced neuroprotection.

PMID- 17498672
TI  - Vibrotactile adaptation fails to enhance spatial localization in adults with
      autism.
AB  - A recent study [Tannan, V., Tommerdahl, M., Whitsel, B.L., 2006. Vibrotactile
      adaptation enhances spatial localization. Brain Res. 1102(1), 109-116 (Aug 2)]
      showed that pre-exposure of a skin region to a 5 s 25 Hz flutter stimulus
      ("adaptation") results in an approximately 2-fold improvement in the ability of
      neurologically healthy human adults to localize mechanical stimulation delivered
      to the same skin region that received the adapting stimulation. Tannan et al.
      [Tannan, V., Tommerdahl, M., Whitsel, B.L., 2006. Vibrotactile adaptation
      enhances spatial localization. Brain Res. 1102(1), 109-116 (Aug 2)] proposed that
      tactile spatial discriminative performance is improved following adaptation
      because adaptation is accompanied by an increase in the spatial contrast in the
      response of contralateral primary somatosensory cortex (SI) to mechanical skin
      stimulation--an effect identified in previous imaging studies of SI cortex in
      anesthetized non-human primates [e.g., Simons, S.B., Tannan, V., Chiu, J.,
      Favorov, O.V., Whitsel, B.L., Tommerdahl, M, 2005. Amplitude-dependency of
      response of SI cortex to flutter stimulation. BMC Neurosci. 6(1), 43 (Jun 21) ;
      Tommerdahl, M., Favorov, O.V., Whitsel, B.L., 2002. Optical imaging of intrinsic
      signals in somatosensory cortex. Behav. Brain Res. 135, 83-91; Whitsel, B.L.,
      Favorov, O.V., Tommerdahl, M., Diamond, M., Juliano, S., Kelly, D., 1989. Dynamic
      processes govern the somatosensory cortical response to natural stimulation. In:
      Lund, J.S., (Ed.), Sensory Processing in the Mammalian Brain. Oxford Univ. Press,
      New York, 79-107]. In the experiments described in this report, a paradigm
      identical to that employed previously by Tannan et al. [Tannan, V., Tommerdahl,
      M., Whitsel, B.L., 2006. Vibrotactile adaptation enhances spatial localization.
      Brain Res. 1102(1), 109-116 (Aug 2)] was used to study adults with autism. The
      results demonstrate that although cutaneous localization performance of adults
      with autism is significantly better than the performance of control subjects when
      the period of adapting stimulation is short (i.e., 0.5 s), tactile spatial
      discriminative capacity remained unaltered in the same subjects when the duration
      of adapting stimulation was increased (to 5 s). Both the failure of prior history
      of tactile stimulation to alter tactile spatial localization in adults with
      autism, and the better-than-normal tactile localization performance of adults
      with autism when the period of adaptation is short are concluded to be
      attributable to the deficient cerebral cortical GABAergic inhibitory
      neurotransmission characteristic of this disorder.

PMID- 17498673
TI  - Cholecystokinin-2 receptors modulate freezing and escape behaviors evoked by the
      electrical stimulation of the rat dorsolateral periaqueductal gray.
AB  - Systemic injection of the cholecystokinin type 2 (CCK(2)) receptor agonist CCK-4
      evokes panic attacks in humans and facilitates the expression of a panic-related
      defensive behavior, escape, in rats. Given the prominent role attributed to the
      dorsal periaqueductal gray (dPAG) in the pathophysiology of panic, this midbrain
      area has been assumed to be one of the key regions mediating these effects of CCK
      4. However, only a few studies have directly investigated the role of dPAG CCK(2)
      receptors in the regulation of panic-related behaviors. Even more
      disappointingly, the results of these investigations have been far from
      conclusive. In the present study we further addressed this issue by evaluating
      the effect of the intra-dorsolateral periaqueductal gray (dlPAG) injection of CCK
      4 on two panic-related defensive behaviors, freezing and escape, evoked in male
      Wistar rats by the electrical stimulation of the dlPAG. The effects of CCK-4
      (0.005-0.5 microg/0.2 microl) were compared to those caused by the local
      microinjection of the CCK(2) receptor antagonist LY225910 (0.001-1.0 microg/0.2
      microl). The results showed that whereas CCK-4 facilitated the expression of both
      freezing and escape behaviors, LY225910 had the opposite effect. Pretreatment
      with an ineffective dose of LY225910 prevented the panicogenic-like effect of CCK
      4. These results strengthen the view that CCK(2) receptors located in the dlPAG
      are involved in the regulation of panic-related behaviors and may mediate the
      effect of CCK-4 on panic.

PMID- 17498674
TI  - Physicochemical and biological properties of 6(1),6(3),6(5)-tri-O-alpha-maltosyl
      cyclomaltoheptaose (6(1),6(3),6(5)-tri-O-alpha-maltosyl-beta-cyclodextrin).
AB  - A unique multibranched cyclomaltooligosaccharide (cyclodextrin, CD) of
      6(1),6(3),6(5)-tri-O-alpha-maltosyl-cyclomaltoheptaose [6(1),6(3),6(5)-tri-O
      alpha-maltosyl-beta-cyclodextrin, (G(2))(3)-betaCD] was prepared. The
      physicochemical and biological properties of (G(2))(3)-betaCD were determined
      together with those of monobranched CDs (6-O-alpha-D-glucopyranosyl-alpha
      cyclodextrin (G(1)-alphaCD), 6-O-alpha-D-glucopyranosyl-beta-cyclodextrin (G(1)
      betaCD), and 6-O-alpha-maltosyl-beta-cyclodextrin (G(2)-betaCD)). NMR spectra of
      (G(2))(3)-betaCD were measured using various 2D NMR techniques. The solubility of
      (G(2))(3)-betaCD in water and MeOH-water solutions was extremely high in
      comparison with nonbranched betaCD and was about the same as that of the other
      monobranched betaCDs. The formation of an inclusion complex of (G(2))(3)-betaCD
      with stereoisomers (estradiol, retinoic acid, quinine, citral, and glycyrrhetinic
      acid) depends on the cis-trans isomers of guest compounds. The cis isomers of
      estradiol, retinoic acid, and glycyrrhetinic acid were included more than their
      trans isomers, while the trans isomers of citral and quinine fit more tightly
      than their cis isomers. (G(2))(3)-betaCD was the most effective host compound in
      the cis-trans resolution of glycyrrhetinic acid. Among the branched betaCDs,
      (G(2))(3)-betaCD exhibited the weakest hemolytic activity in human erythrocytes
      and showed negligible cytotoxicity in Caco-2 cells up to 200 microM. These
      results indicate unique characteristics of (G(2))(3)-betaCD in some biological
      responses of cultured cells.

PMID- 17498675
TI  - Solid-state hydrolysis of cellulose and methyl alpha- and beta-D-glucopyranosides
      in presence of magnesium chloride.
AB  - Solid-state hydrolysis proceeded with cellulose and methyl alpha- and beta-D
      glucopyranosides in the presence of hydrated magnesium chloride. This reaction
      was effective even at >100 degrees C since the hydrated water, which is held by
      MgCl(2) up to >200 degrees C, is utilized as a nucleophile. Excess water made
      this reaction ineffective due to the competition between water and sugar oxygen
      atoms in coordinating with Mg(2+), a Lewis acid. Consequently, this hydrolysis
      reaction is characteristic of solid-state reactions.

PMID- 17498676
TI  - Activation of endothelial nitric oxide synthase by dietary isoflavones: role of
      NO in Nrf2-mediated antioxidant gene expression.
AB  - The endothelium plays a key role in the maintenance of vascular homeostasis, and
      increased oxidative stress in vascular disease leads to reduced nitric oxide
      bioavailability and impaired endothelium-dependent relaxation of resistance
      vessels. Although epidemiological evidence suggests that diets containing high
      amounts of natural antioxidants afford protection against coronary heart disease
      (CHD), antioxidant supplementation trials have largely reported only marginal
      health benefits. There is controversy concerning the cardiovascular benefits of
      prolonged estrogen/progestin or soy isoflavone therapy for postmenopausal women
      and patients with an increased risk of CHD. Research on the potential health
      benefits of soy isoflavones and other polyphenols contained in red wine, green
      and black tea and dark chocolate developed rapidly during the 1990's, and recent
      clinical trials and studies in animal models and cultured endothelial cells
      provide important and novel insights into the mechanisms by which dietary
      polyphenols afford protection against oxidative stress. In this review, we
      highlight that NO and reactive oxygen radicals may mediate dietary polyphenol
      induced activation of Nrf2, which in turn triggers antioxidant response element
      (ARE) driven transcription of phase II detoxifying and antioxidant defense
      enzymes in vascular cells.

PMID- 17498677
TI  - Role of ERK1/2 and PI3-K in the regulation of CTGF-induced ILK expression in HK-2
      cells.
AB  - BACKGROUND: Previous studies revealed that integrin-linked kinase (ILK), an
      intracellular serine/threonine protein kinase, is a critical mediator for tubular
      epithelial to mesenchymal transition (EMT), and likely plays an important role in
      the pathogenesis of chronic kidney fibrosis. However, the exact signal pathway
      has not been well understood. In this study, we investigated the role of
      extracellular regulating kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase
      (PI3-K) in the regulation of ILK expression by connective tissue growth factor
      (CTGF) in HK-2 cells. METHODS: Experiments were performed on transformed (human
      kidney cell (HKC)-clone 2) human proximal tubular epithelial cells (PTECs).
      Induction of ILK in response to CTGF was studied at the mRNA level by real-time
      PCR and protein by immunoblotting. Chemical inhibitors were used to assess the
      role of MEK/ERK1/2, PI3-K, and P38 MAPK signaling pathways in induction of ILK by
      CTGF. RESULTS: CTGF induced ILK protein expression in HK-2 cells in a time- and
      dose-dependent manner. There was a 5.638-fold (control: 1.000+/-0.290, 50 ng/ml:
      5.638+/-1.200; *P<0.05 vs. control) and 5.740-fold (0 h: 1.000+/-0.498, 48 h:
      5.740+/-1.465, *P<0.05 vs. control) increase compared to control respectively.
      CTGF-induced ILK expression was partially reduced by inhibiting ERK1/2 and PI3-K
      activation. There was no influence of ILK expression by inhibiting P38 MAPK
      activation when cells treated with CTGF. CONCLUSION: CTGF induces the expression
      of ILK protein in HK-2 cells. This induction is partially dependent on MEK/ERK1/2
      and PI3-K signaling pathways. Inhibiting CTGF-induced ILK by targeting PI3-K
      and/or MEK/ERK1/2 signaling pathways could be of therapeutic value in renal
      fibrosis.

PMID- 17498678
TI  - Percentage non-caeruloplasmin bound copper.
AB  - OBJECTIVES: To compare percentage non-caeruloplasmin bound copper (%NCC) to
      generally accepted values. DESIGN AND METHODS: Using data for 338 normal
      individual patients, we calculated the %NCC. RESULTS: The %NCC ranged (median)
      from -59.75% to 51.98% (8.75%) respectively. The non-parametric reference
      interval was -23.44% to 22.99% with 43.8% of the %NCC values >10%. CONCLUSIONS:
      We found the %NCC to be higher than generally accepted. This may be due to
      uncertainty from precision, bias and specificity.

PMID- 17498679
TI  - Tubby protein in human lymphocytes from normal weight and obese subjects.
AB  - OBJECTIVES: The presence of tubby protein in human lymphocytes was investigated
      and their electrophoretic mobility property between normal weight and obese
      subjects was compared. DESIGN AND METHODS: 2-DE proteome map of lymphocytes has
      been generated and western blot analysis was conducted using anti-tub polyclonal
      antibody. RESULTS AND CONCLUSIONS: We found the presence of tubby protein both in
      normal weight and in obese subjects; however in the latter an isoelectric point
      shift toward the acidic end was observed.

PMID- 17498680
TI  - An ELISA for plasma retinol-binding protein using monoclonal and polyclonal
      antibodies: plasma variation in normal and insulin resistant subjects.
AB  - OBJECTIVES: Plasma retinol-binding protein (RBP) has been linked to insulin
      resistance and cardiovascular risk, yet little is know of its natural variation
      in plasma. We examined this in normal subjects and compared plasma levels and
      variability in lean subjects and subjects with the metabolic syndrome. METHODS:
      We established an "in house" ELISA for plasma RBP and measured levels in 20
      normal subjects over daylight hours and 2 subject groups, either lean or
      classified with the metabolic syndrome. RESULTS: Plasma RBP in normal subjects
      did not vary over the day with no differences between males and females. There
      was also no difference in plasma RBP levels and between the age- and sex-matched
      lean subjects compared to the metabolic syndrome group. CONCLUSION: The lack of
      variation in plasma RBP in normal subjects and the lack of difference between
      plasma RBP in normal and metabolic syndrome subjects suggest the link between
      plasma RBP and insulin resistance is tenuous. Investigating a large cohort over
      the diabetic non-diabetic spectrum may clarify this issue.

PMID- 17498681
TI  - Can word formation be understood or understanded by semantics alone?
AB  - Arguments concerning the relative role of semantic and grammatical factors in
      word formation have proven to be a wedge issue in current debates over the nature
      of linguistic representation and processing. In the present paper, we re-examine
      claims by Ramscar [Ramscar, M. (2002). The role of meaning in inflection: Why the
      past tense does not require a rule. Cognitive Psychology, 45, 45-94.] that it is
      semantic rather than grammatical factors that influence the choice of regular or
      irregular past tense forms for English verbs. In Experiment 1, we first
      replicated Ramscar's (2002) experiment, which showed semantic influences on
      choice of past tense inflection. A novel verb, splink, was introduced in a
      semantic context that was reminiscent of an existing regular or irregular rhyme
      verb: blink or drink. Participants favored the past tense form (splinked or
      splank) that matched that of the semantically similar verb. In Experiment 2, we
      introduced novel verbs in a context suggesting that they were grammatically
      derived from nouns (i.e., denominals). Some current symbolic processing models
      propose that regular past tense forms should be preferred for such forms. When
      Ramscar's (2002) original contexts for derivational verbs were re-tested in this
      condition, we replicated his failure to find a preference for regular past tense
      forms. However, when the contexts were modified to make the grammatical process
      more salient, we did find a preference for regular past tense forms, suggesting
      that the derivational status might have been ambiguous in the original materials.
      In Experiment 3, we tested whether acceptability ratings for regular or irregular
      past tense forms of grammatically derived verbs could be explained by semantic
      distance metrics or by ratings of noun-to-verb derivational status. Ratings of
      semantic distance and grammatical derivation were orthogonal factors in
      Experiment 3. Only derivational status predicted acceptability ratings for
      regular past tense forms. Taken together, the present results suggest that
      semantic factors do not explain the regularization of irregular verbs in
      derivational contexts, although semantic factors can affect the choice of past
      tense forms in certain circumstances.

PMID- 17498682
TI  - Cyclin A1-deficient mice lack histone H3 serine 10 phosphorylation and exhibit
      altered aurora B dynamics in late prophase of male meiosis.
AB  - Male mice lacking cyclin A1 protein are sterile. Their sterility results from an
      arrest in the meiotic cell cycle of spermatocytes, which we now identify as
      occurring at late diplotene, immediately before diakinesis. The stage of arrest
      in cyclin A1-deficient mice is distinct from the arrest seen in spermatocytes
      that are deficient in its putative catalytic partner Cdk2, which occurs much
      earlier in pachytene. The arrest in cyclin A1-deficient spermatocytes is also
      accompanied by an unusual clustering of centromeric heterochromatin. Consistent
      with a possible defect in the centromeric region, immunofluorescent staining of
      cyclin A1 protein shows localization in the region of the centromere.
      Phosphorylation of histone H3 at serine 10 in pericentromeric heterochromatin,
      which normally occurs in late diplotene, is reduced in spermatocytes from
      heterozygous Ccna1(+/-) testes and completely absent in spermatocytes with no
      cyclin A1 protein. Concomitantly, the levels of pericentromeric aurora B kinase,
      known to phosphorylate histone H3 during meiosis, are partially reduced in
      spermatocytes from testes of heterozygous mice and further reduced in homozygous
      null spermatocytes. These data suggest a critical and concentration-dependent
      function for cyclin A1 in the pericentromeric region in late diplotene of
      meiosis, perhaps in assembly or function of the passenger protein complex.

PMID- 17498683
TI  - Glycosphingolipids with extended sugar chain have specialized functions in
      development and behavior of Drosophila.
AB  - Glycosphingolipids (GSL) are glycosylated polar lipids in cell membranes
      essential for development of vertebrates as well as Drosophila. Mutants that
      impair enzymes involved in biosynthesis of GSL sugar chains provide a means to
      assess the functions of the sugar chains in vivo. The Drosophila
      glycosyltransferases Egghead and Brainiac are responsible for the 2nd and 3rd
      steps of GSL sugar chain elongation. Mutants lacking these enzymes are lethal and
      the nature of the defects that occur has suggested that GSL might impact on
      signaling by the Notch and EGFR pathways. Here we report on characterization of
      enzymes involved in the 4th and 5th steps of GSL sugar chain elongation in vitro
      and explore the biological consequences of removing the enzymes involved in step
      4 in vivo. Two beta4-N-Acetylgalactosyltransferase enzymes can carry out step 4
      (beta4GalNAcTA and beta4GalNAcTB), and while they may have overlapping activity,
      the mutants produce distinct phenotypes. The beta4GalNAcTA mutant displays
      behavioral defects, which are also observed in viable brainiac mutants,
      suggesting that proper locomotion and coordination primarily depend on GSL
      elongation. beta4GalNAcTB mutant animal shows ventralization of ovarian follicle
      cells, which is caused by defective EGFR signaling between the oocyte and the
      dorsal follicle cells to specify dorsal fate. GSL sequentially elongated by Egh,
      Brn and beta4GalNAcTB in the oocyte contribute to this signaling pathway. Despite
      the similar enzymatic activity, we provide evidence that the two enzymes are not
      functionally redundant in vivo, but direct distinct developmental functions of
      GSL.

PMID- 17498684
TI  - Upd/Jak/STAT signaling represses wg transcription to allow initiation of
      morphogenetic furrow in Drosophila eye development.
AB  - The initiation of retinal development in Drosophila begins at the posterior
      center (PC) of the eye disc margin. The front of the differentiation wave,
      recognized as a morphogenetic furrow (MF), moves from posterior to anterior. What
      determines MF initiates from the specific PC site is still unclear. The unpaired
      (upd) gene is expressed at PC at early third instar, just before the time of MF
      initiation. Therefore, upd is expressed at the appropriate time and location for
      a specific role in defining the site of MF initiation. upd encodes a ligand for
      the Jak/STAT signaling pathway. In this report, we showed that the Upd/Jak/STAT
      signaling is required and sufficient to determine MF initiation. This is
      primarily achieved by repressing the transcription of wingless (wg), which is
      known to block MF initiation.

PMID- 17498685
TI  - Wnt signaling is required for antero-posterior patterning of the planarian brain.
AB  - Wnt signaling functions in axis formation and morphogenesis in various animals
      and organs. Here we report that Wnt signaling is required for proper brain
      patterning during planarian brain regeneration. We showed here that one of the
      Wnt homologues in the planarian Dugesia japonica, DjwntA, was expressed in the
      posterior region of the brain. When DjwntA-knockdown planarians were produced by
      RNAi, they could regenerate their heads at the anterior ends of the fragments,
      but formed ectopic eyes with irregular posterior lateral branches and brain
      expansion. This suggests that the Wnt signal may be involved in antero-posterior
      (A-P) patterning of the planarian brain, as in vertebrates. We also investigated
      the relationship between the DjwntA and nou-darake/FGFR signal systems, as
      knockdown planarians of these genes showed similar phenotypes. Double-knockdown
      planarians of these genes did not show any synergistic effects, suggesting that
      the two signal systems function independently in the process of brain
      regeneration, which accords with the fact that nou-darake was expressed earlier
      than DjwntA during brain regeneration. These observations suggest that the nou
      darake/FGFR signal may be involved in brain rudiment formation during the early
      stage of head regeneration, and subsequently the DjwntA signal may function in A
      P patterning of the brain rudiment.

PMID- 17498686
TI  - Synergy between delta9-tetrahydrocannabinol and morphine in the arthritic rat.
AB  - We have shown in past isobolographic studies that a small amount of Delta(9)
      tetrahydrocannabinol (Delta(9)-THC) can enhance morphine antinociception in mice.
      However, previous studies of the Delta(9)-THC/morphine interaction were performed
      using normal mice or rats and evaluated acute thermal antinociception. Less is
      known about cannabinoid and opioid interactions involved in mechanical
      nociception and in chronic inflammatory pain models, such as Freund's complete
      adjuvant-induced arthritic model. One fixed-ratio combination was chosen for
      testing the interaction between Delta(9)-THC and morphine in the Freund's
      adjuvant-induced arthritic model. This combination represented a 1:1 ratio of the
      drugs and thus consisted of equieffective doses ranging from 0.1 to 5 mg/kg
      Delta(9)-THC and from 0.1 to 5 mg/kg morphine. The combination ED(50) value for
      the fixed ratios (total dose) in relation to the ED(50) value of the drugs alone
      was determined. The isobolographic analysis indicated a synergistic interaction
      between Delta(9)-THC and morphine in both the non-arthritic and the arthritic
      rats. Since Freund's adjuvant-induced alteration in endogenous opioid tone has
      been previously shown, our data indicate that such changes did not preclude the
      use of Delta(9)-THC and morphine in combination. As with acute preclinical pain
      models in which the Delta(9)-THC/morphine combination results in less tolerance
      development, the implication of the study for chronic pain conditions is
      discussed.

PMID- 17498687
TI  - Chronic 3,4-methylenedioxymethamphetamine treatment suppresses cell proliferation
      in the adult mouse dentate gyrus.
AB  - We investigated the influence of chronic 3,4-methylenedioxymethamphetamine (MDMA)
      treatment on cell proliferation in the adult dentate gyrus. Mice were orally
      treated with MDMA (1.25 mg/kg-40 mg/kg) or saline for 30 days. To label dividing
      cells, mice were given 5-bromo-2'-deoxyuridine (BrdU) for 4 days from the day
      after the last administration of MDMA, and their brains were examined 24 h later.
      MDMA dose-dependently induced a decrease in the number of BrdU-positive cells in
      the male and female dentate gyrus. Our results suggest that chronic exposure to
      MDMA suppresses cell proliferation in the dentate gyrus.

PMID- 17498688
TI  - p63 - Key molecule in the early phase of epithelial abnormality in idiopathic
      pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common lung disease predisposing
      lung cancer. To clarify the early phase of epithelial abnormalities in IPF, we
      used an in vitro squamous metaplasia model, transforming growth factor beta1 (TGF
      beta1)-treated airway epithelial cells (BEAS-2B). The model repeated the
      expression of squamous epithelial character, such as involucrin, and keratin 6
      and 14. DNA microarray analysis disclosed a unique expression signature in TGF
      beta1-treated airway epithelial cells, 20 specifically up-regulated genes
      including p63, jagged 1 (jag1) and the genes of structure proteins. Western
      blotting and RT-PCR analysis revealed that DeltaNp63alpha was the dominant
      isoform of p63 in our experimental model. Immunohistochemical analysis
      demonstrated the expression of p63 and jag1 in lung tissues of IPF. Inhibition of
      p63 with siRNA caused the down-regulation of jag1 expression, but not of
      involucrin, or keratin 6 and 14. Interestingly, the up-regulation of p63 was
      totally suppressed by N-acetyl-l-cysteine (NAC), but not by dexamethasone or
      pirfenidone. Thus, the p63-jag1 pathway may be up-regulated at an early phase of
      epithelial abnormalities in IPF, which can be overcome by NAC even in the TGF
      beta1-rich milieu.

PMID- 17498689
TI  - Conserved C-terminal domains of mCenp-F (LEK1) regulate subcellular localization
      and mitotic checkpoint delay.
AB  - Centromeric Protein-F (Cenp-F) family members have been identified in organisms
      from yeast to human. Cenp-F proteins are a component of kinetochores during
      mitosis, bind to the Rb family of tumor suppressors, and have regulatory effects
      on the cell cycle and differentiation; however, their role in these processes has
      not been resolved. Here, we provide evidence that the role of murine Cenp-F
      (mCenp-F, also known as LEK1) remains largely conserved and that the domains
      within the C-terminus collectively function to regulate the G2/M cell cycle
      checkpoint. Overexpression of the C-terminal domain of mCenp-F decreases DNA
      synthesis. Analyses of deletion mutants of mCenp-F reveal that the complete C
      terminal domain is required to delay cell cycle progression at G2/M. Signal
      transduction pathway profiling experiments indicate that the mCenp-F-mediated
      cell cycle delay does not involve transcriptional activity of key cell cycle
      regulators such as Rb, E2F, p53, or Myc. However, endogenous mCenp-F colocalizes
      with pRb and p107, which demonstrates in vivo protein-protein interaction during
      cell division. These observations suggest that the domains of the C-terminus of
      mCenp-F have a conserved function in control of mitotic progression through
      protein-protein interaction with pocket proteins, thus providing a direct
      connection between cell cycle regulation and mitotic progression.

PMID- 17498691
TI  - The motility and dynamic properties of intermediate filaments and their
      constituent proteins.
AB  - Intermediate filament (IF) proteins exist in multiple structural forms within
      cells including mature IF, short filaments or 'squiggles', and non-filamentous
      precursors called particles. These forms are interconvertible and their relative
      abundance is IF type, cell type- and cell cycle stage-dependent. These structures
      are often associated with molecular motors, such as kinesin and dynein, and are
      therefore capable of translocating through the cytoplasm along microtubules. The
      assembly of mature IF from their precursor particles is also coupled to
      translation. These dynamic properties of IF provide mechanisms for regulating
      their reorganization and assembly in response to the functional requirements of
      cells. The recent findings that IF and their precursors are frequently associated
      with signaling molecules have revealed new functions for IF beyond their more
      traditional roles as mechanical integrators of cells and tissues.

PMID- 17498690
TI  - Role of phosphorylation on the structural dynamics and function of types III and
      IV intermediate filaments.
AB  - Phosphorylation of types III and IV intermediate filaments (IFs) is known to
      regulate their organization and function. Phosphorylation of the amino-terminal
      head domain sites on types III and IV IF proteins plays a key role in the
      assembly/disassembly of IF subunits into 10 nm filaments, and influences the
      phosphorylation of sites on the carboxyl-terminal tail domain. These
      phosphorylation events are largely under the control of second messenger
      dependent protein kinases and provide the cells a mechanism to reorganize the IFs
      in response to the changes in second messenger levels. In mitotic cells, Cdk1,
      Rho kinase, PAK1 and Aurora-B kinase are believed to regulate vimentin and glial
      fibrillary acidic protein phosphorylation in a spatio-temporal manner. In
      neurons, the carboxyl-terminal tail domains of the NF-M and NF-H subunits of
      heteropolymeric neurofilaments (NFs) are highly phosphorylated by proline
      directed protein kinases. The phosphorylation of carboxyl-terminal tail domains
      of NFs has been suspected to play roles in forming cross-bridges between NFs and
      microtubules, slowing axonal transport and promoting their integration into
      cytoskeleton lattice and, in doing so, to control axonal caliber and stabilize
      the axon. The role of IF phosphorylation in disease pathobiology is discussed.

PMID- 17498692
TI  - Reactive nitrogen and oxygen species activate different sphingomyelinases to
      induce apoptosis in airway epithelial cells.
AB  - Airway epithelial cells are constantly exposed to environmental insults such as
      air pollution or tobacco smoke that may contain high levels of reactive nitrogen
      and reactive oxygen species. Previous work from our laboratory demonstrated that
      the reactive oxygen species (ROS), hydrogen peroxide (H(2)O(2)), specifically
      activates neutral sphingomyelinase 2 (nSMase2) to generate ceramide and induce
      apoptosis in airway epithelial cells. In the current study we examine the
      biological consequence of exposure of human airway epithelial (HAE) cells to
      reactive nitrogen species (RNS). Similar to ROS, we hypothesized that RNS may
      modulate ceramide levels in HAE cells and induce apoptosis. We found that nitric
      oxide (NO) exposure via the NO donor papa-NONOate, failed to induce apoptosis in
      HAE cells. However, when papa-NONOate was combined with a superoxide anion donor
      (DMNQ) to generate peroxynitrite (ONOO(-)), apoptosis was observed. Similarly
      pure ONOO(-)-induced apoptosis, and ONOO(-)-induced apoptosis was associated with
      an increase in cellular ceramide levels. Pretreatment with the antioxidant
      glutathione did not prevent ONOO(-)-induced apoptosis, but did prevent H(2)O(2)
      induced apoptosis. Analysis of the ceramide generating enzymes revealed a
      differential response by the oxidants. We confirmed our findings that H(2)O(2)
      specifically activated a neutral sphingomyelinase (nSMase2). However, ONOO(-)
      exposure did not affect neutral sphingomyelinase activity; rather, ONOO(-)
      specifically activated an acidic sphingomyelinase (aSMase). The specificity of
      each enzyme was confirmed using siRNA to knockdown both nSMase2 and aSMase.
      Silencing nSMase2 prevented H(2)O(2)-induced apoptosis, but had no effect on
      ONOO(-)-induced apoptosis. On the other hand, silencing of aSMase markedly
      impaired ONOO(-)-induced apoptosis, but did not affect H(2)O(2)-induced
      apoptosis. These findings support our hypothesis that ROS and RNS modulate
      ceramide levels to induce apoptosis in HAE cells. However, we found that
      different oxidants modulate different enzymes of the ceramide generating
      machinery to induce apoptosis in airway epithelial cells. These findings add to
      the complexity of how oxidative stress promotes lung cell injury.

PMID- 17498693
TI  - The mammalian Ced-1 ortholog MEGF10/KIAA1780 displays a novel adhesion pattern.
AB  - Ced-1 protein is a Caenorhabditis elegans cell surface receptor involved in
      phagocytosis of dead cells. The gene encoding the mammalian ortholog of Ced-1 is
      yet to be identified. Here, we describe a potential candidate: human MEGF10.
      MEGF10 has the overall domain organization of Ced-1, containing a signal peptide,
      a EMI domain, 17 atypical EGF-like repeats, a transmembrane domain, and a
      cytoplasmic domain with NPXY and YXXL motifs. MEGF10-EGFP fusion protein
      expressed in HEK293 cells produced an irregular, mosaic-like pattern on the
      surface of coated glass. Protruded MEGF10 bound tightly to the glass, in effect
      "pinning" the cytoplasmic membrane firmly onto the glass, thereby restricting
      cell motility. These cells also took on a flat appearance. Although MEGF10-EGFP
      localized throughout the cytoplasmic membrane, no MEGF10-EGFP was found in
      lamellipodia. The MEGF10-EGFP signal was surrounded by a 1-2-microm-wide dark
      strip lacking EGFP. Expression analyses of various MEGF10 deletion mutants
      revealed that the irregular, mosaic-like adhesion pattern characteristic of
      MEGF10 family members is due to concerted interactions between the EMI and 17
      atypical EGF-like domains. Co-culturing of MEGF10-EGFP-expressing cells with
      apoptotic cells revealed that MEGF10 protein accumulated around the contact
      region during engulfment of apoptotic cells.

PMID- 17498695
TI  - Dual roles of intermediate filaments in apoptosis.
AB  - New roles have emerged recently for intermediate filaments (IFs), namely in
      modulating cell adhesion and growth, and providing resistance to various forms of
      stress and to apoptosis. In this context, we first summarize findings on the IF
      association with the cell response to mechanical stress and growth stimulation,
      in light of growth-related signaling events that are relevant to death-receptor
      engagement. We then address the molecular mechanisms by which IFs can provide
      cell resistance to apoptosis initiated by death-receptor stimulation and to
      necrosis triggered by excessive oxidative stress. In the same way, we examine IF
      involvement, along with cytolinker participation, in sequential caspase-mediated
      protein cleavages that are part of the overall cell death execution, particularly
      those that generate new functional IF protein fragments and uncover neoantigen
      markers. Finally, we report on the usefulness of these markers as diagnostic
      tools for disease-related aspects of apoptosis in humans. Clearly, the data
      accumulated in recent years provide new and significant insights into the
      multiple functions of IFs, particularly their dual roles in cell response to
      apoptotic insults.

PMID- 17498694
TI  - GFAP and its role in Alexander disease.
AB  - Here we review how GFAP mutations cause Alexander disease. The current data
      suggest that a combination of events cause the disease. These include: (i) the
      accumulation of GFAP and the formation of characteristic aggregates, called
      Rosenthal fibers, (ii) the sequestration of the protein chaperones alpha B
      crystallin and HSP27 into Rosenthal fibers, and (iii) the activation of both Jnk
      and the stress response. These then set in motion events that lead to Alexander
      disease. We discuss parallels with other intermediate filament diseases and
      assess potential therapies as part of this review as well as emerging trends in
      disease diagnosis and other aspects concerning GFAP.

PMID- 17498696
TI  - A muscarinic cholinergic antagonist and a dopamine agonist rapidly increase ZENK
      mRNA expression in the form-deprived chicken retina.
AB  - Increases in the expression of the immediate early gene ZENK in the retina,
      measured by changes in the levels of mRNA and protein immunoreactivity, are
      amongst the most rapid responses so far measured to conditions that decrease the
      rate of eye growth in chickens. Our aim was to determine whether atropine, a
      muscarinic cholinergic antagonist, and 2-amino-6,7-dihydroxy-1,2,3,4
      tetrahydronaphthalene hydrobromide, a dopamine agonist, which are known to block
      excessive eye growth, produce similar changes in ZENK expression. Form
      deprivation resulted in significant down-regulation of the expression of retinal
      ZENK mRNA within 1 h of fitting the diffusers, whereas removal of the diffusers
      from the eyes of chickens that had developed form-deprivation myopia resulted in
      significant up-regulation of retinal ZENK expression within 1 h. When atropine
      (10 microL of 25 mM solution) and 2-amino-6,7-dihydroxy-1,2,3,4
      tetrahydronaphthalene hydrobromide (10 microL of a 10 mM solution) were injected
      intravitreally, just prior to fitting the diffusers, the down-regulation of
      retinal ZENK mRNA caused by form-deprivation was reversed. This resulted in
      levels of ZENK mRNA higher than in control or contralateral control eyes. The
      doses were chosen because they are known to block the excessive axial elongation
      induced by form-deprivation, without affecting the growth of control eyes.
      Neither agent had any effect on retinal ZENK expression within this time period
      when injected into control eyes. These results suggest that both muscarinic
      acetylcholine antagonists and dopamine agonists act early in the signal cascade
      controlling eye growth, possibly within the retina itself.

PMID- 17498697
TI  - Pallidal stimulation modifies after-effects of paired associative stimulation on
      motor cortex excitability in primary generalised dystonia.
AB  - OBJECTIVE: To determine the effect of globus pallidus internus (GPi) deep brain
      stimulation (DBS) on motor cortex plasticity in patients with primary generalised
      dystonia. METHODS: We studied 10 patients with primary generalised dystonia (5
      DYT1+, 5 idiopathic, 5 female, mean age 42) following GPi DBS and 10 healthy
      subjects. Motor cortex plasticity was assessed using transcranial magnetic
      stimulation (TMS) paired associative stimulation (PAS) of motor cortex and median
      nerve, a method which has been shown in healthy subjects to produce LTP-like
      effects. Thresholds and TMS intensity to produce a resting motor evoked potential
      (MEP) of 1 mV were determined. Resting MEP amplitude and stimulus response curves
      were recorded before and after PAS. Patients were recorded ON and OFF DBS in
      separate sessions. RESULTS: The mean TMS intensity to produce a resting MEP of 1
      mV was 54% of maximum stimulator output when OFF and 52% ON DBS. Fifteen minutes
      after PAS the resting MEP amplitude increased in patients OFF DBS and in control
      subjects whereas it decreased in patients ON DBS. Similarly, after PAS, the mean
      amplitude of the stimulus response curve increased OFF DBS, but this effect was
      abolished with DBS ON. Furthermore, patients who had the largest clinical
      response to chronic DBS also had the largest difference in the effect of PAS with
      DBS ON vs. OFF. CONCLUSIONS: After PAS, patients with primary generalised
      dystonia showed a similar pattern of increased motor cortex excitability as
      healthy subjects when GPi DBS was OFF but not with GPi DBS ON. These results
      suggest that GPi DBS may reduce LTP-like motor cortex plasticity, which could
      contribute to its mechanism of action in dystonia.

PMID- 17498698
TI  - Involvement of thrombin and mitogen-activated protein kinase pathways in
      hemorrhagic brain injury.
AB  - Thrombin is thought to play an important role in brain damage associated with
      intracerebral hemorrhage (ICH). We previously showed that activation of mitogen
      activated protein (MAP) kinases and recruitment of microglia are crucial for
      thrombin-induced shrinkage of the striatal tissue in vitro and thrombin-induced
      striatal damage in vivo. Here we investigated whether the same mechanisms are
      involved in ICH-induced brain injury. A substantial loss of neurons was observed
      in the center and the peripheral region of hematoma at 3 days after ICH induced
      by intrastriatal injection of collagenase in adult rats. Intracerebroventricular
      injection of argatroban or cycloheximide, both of which prevent thrombin
      cytotoxicity in vitro, exhibited a significant neuroprotective effect against ICH
      induced injury. ICH-induced neuron loss was also prevented by a MAP kinase kinase
      inhibitor (PD98059) and a c-Jun N-terminal kinase inhibitor (SP600125). These
      drugs had no effect on hematoma size or ICH-induced brain edema. Activation of
      extracellular signal-regulated kinase in response to ICH was observed in both
      neurons and microglia. Despite their neuroprotective effects, MAP kinase
      inhibitors did not decrease the number of terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling (TUNEL)-positive cells appearing after ICH.
      Identification of cell types revealed that TUNEL staining occurred prominently in
      neurons but not in microglia, whereas inhibition of MAP kinases resulted in
      appearance of TUNEL staining in microglia. These results suggest that thrombin
      and the activation of MAP kinases are involved in ICH-induced neuronal injury,
      and that neuroprotective effects of MAP kinases are in part mediated by
      arrestment of microglial activities.

PMID- 17498699
TI  - Is erythropoietin a potential therapy for amyotrophic lateral sclerosis?

PMID- 17498700
TI  - Manifold active-state conformations in GPCRs: agonist-activated constitutively
      active mutant AT1 receptor preferentially couples to Gq compared to the wild-type
      AT1 receptor.
AB  - The angiotensin II type I (AT(1)) receptor mediates regulation of blood pressure
      and water-electrolyte balance by Ang II. Substitution of Gly for Asn(111) of the
      AT(1) receptor constitutively activates the receptor leading to Gq-coupled IP(3)
      production independent of Ang II binding. The Ang II-activated conformation of
      the AT1(N111G) receptor was proposed to be similar to that of the wild-type AT(1)
      receptor, although, various aspects of the Ang II-induced conformation of this
      constitutively active mutant receptor have not been systematically studied. Here,
      we provide evidence that the conformation of the active state of the wild-type
      and the constitutively active AT(1) receptors are different. Upon Ang II binding
      an activated conformation of the wild-type AT(1) receptor activates G protein and
      recruits beta-arrestin. In contrast, the agonist-bound AT1(N111G) mutant receptor
      preferentially couples to Gq and is inadequate in beta-arrestin recruitment.

PMID- 17498701
TI  - Neurexin-1 is required for synapse formation and larvae associative learning in
      Drosophila.
AB  - Neurexins are highly polymorphic cell-surface adhesive molecules in neurons. In
      cultured mammalian cell system, they were found to be involved in synaptogenesis.
      Here, we report for the first time that Drosophila neurexin is required for
      synapse formation and associative learning in larvae. Drosophila genome encodes a
      single functional neurexin (CG7050; Neurexin-1 or Nrx-1), which is a homolog of
      vertebrate alpha-neurexin. Neurexin-1 is expressed in central nervous system and
      highly enriched in synaptic regions of the ventral ganglion and brain. Neurexin-1
      null mutants are viable and fertile, but have shortened lifespan. The synapse
      number is decreased in central nervous system in Neurexin-1 null mutants. In
      addition, Neurexin-1 null mutants exhibit associative learning defect in larvae.

PMID- 17498702
TI  - Targeted deletion of the osteoclast protein-tyrosine phosphatase (PTP-oc)
      promoter prevents RANKL-mediated osteoclastic differentiation of RAW264.7 cells.
AB  - An osteoclastic protein-tyrosine phosphatase, PTP-oc, shares the same gene with a
      renal PTP, Glepp1. This study demonstrated that targeted deletion of PTP-oc
      promoter by homologous recombination in RAW264.7 cells completely abolished PTP
      oc expression without affecting Glepp1 expression. This strategy to inhibit PTP
      oc function has three advantages over commonly used gene knock down strategies
      (e.g., small interference RNA). This strategy: (1) yielded cells completely
      devoid of PTP-oc, (2) had no off-target gene silencing effects, and (3) did not
      affect Glepp1 expression. The inability of PTP-oc-deficient RAW264.7 cells to
      undergo RANKL-mediated osteoclastic differentiation confirmed a regulatory role
      for PTP-oc in RANKL-mediated osteoclast differentiation.

PMID- 17498703
TI  - Identification and characterization of DUSP27, a novel dual-specific protein
      phosphatase.
AB  - A novel human dual-specific protein phosphatase (DSP), designated DUSP27, is here
      described. The DUSP27 gene contains three exons, rather than the predicted 4-14
      exons, and encodes a 220 amino acid protein. DUSP27 is structurally similar to
      other small DSPs, like VHR and DUSP13. The location of DUSP27 on chromosome
      10q22, 50kb upstream of DUSP13, suggests that these two genes arose by gene
      duplication. DUSP27 is an active enzyme, and its kinetic parameters and were
      determined. DUSP27 is a cytosolic enzyme, expressed in skeletal muscle, liver and
      adipose tissue, suggesting its possible role in energy metabolism.

PMID- 17498704
TI  - Divergent microsatellite evolution in the human and chimpanzee lineages.
AB  - Comparison of the complete human genome sequence to one of its closest relatives,
      the chimpanzee genome, provides a unique opportunity for exploring recent
      evolutionary events affecting the microsatellites in these species. A simple
      assumption on microsatellite distribution is that the total length of perfect
      repeats is constant compared to that of imperfect ones regardless of the repeat
      sequence. In this paper, we show that this is valid for most of the chimpanzee
      genome but not for a number of human chromosomes. Our results suggest accelerated
      evolution of microsatellites in the human genome relative to the chimpanzee
      lineage.

PMID- 17498705
TI  - Differential expression and regulation of prostaglandin transporter and metabolic
      enzymes in mouse uterus during blastocyst implantation.
AB  - OBJECTIVE: To examine the spatiotemporal expression and regulation of
      prostaglandin transporter (PGT), 15-hydroxy-PG dehydrogenase (15-PGDH), and
      carbonyl reductase 1 (CBR1) messenger RNA (mRNA) and protein in the mouse uterus
      during embryo implantation and in related models. DESIGN: Experimental animal
      study. SETTING: University research laboratory. ANIMAL(S): Sexually mature female
      Kunming strain white mice. INTERVENTION(S): Delayed and activated implantation,
      artificial decidualization, and subcutaneous injection of progesterone (P) and
      E(2) in ovariectomized mouse. MAIN OUTCOME MEASURE(S): The expression of mRNA and
      protein were detected by in situ hybridization and immunohistochemistry in mouse
      uterus. RESULT(S): Prostaglandin transporter mRNA and protein were expressed in
      the subluminal stroma at implantation site on day 5 of pregnancy and then in
      decidua but were not detected at the interimplantation sites and in
      preimplantation or pseudopregnant uterus. The presence of an active blastocyst
      was required for PGT expression at the implantation site. Both 15-PGDH and CBR1
      mRNA were detected in glandular epithelium on day 4 of pregnancies. The
      expression of 15-PGDH and CBR1 mRNA was also detected in postimplantation
      embryos. CONCLUSION(S): These data suggest that differentially expressed PGT and
      15-PGDH may participate in PG signaling in mouse uterus during implantation and
      decidualization.

PMID- 17498706
TI  - Conservative management of adnexal torsion via transvaginal ultrasound guided
      ovarian cyst aspiration in patients with ovarian hyperstimulation.
AB  - OBJECTIVE: To report the successful conservative management of two patients with
      acute adnexal torsion by ultrasound-guided transvaginal ovarian cystic
      aspiration. DESIGN: Case report. SETTING: A reproductive medical center.
      PATIENTS: Two women with OHSS who had acute lower abdominal pain, nausea, and
      vomiting, and were found to have acute adnexal torsion. INTERVENTION(S): An
      ultrasound-guided transvaginal ovarian cystic aspiration was performed promptly.
      MAIN OUTCOME MEASURE(S): The clinical symptoms of acute adnexal torsion after the
      procedure. RESULT(S): After the cystic aspiration, acute lower abdominal pain,
      nausea, and vomiting were relieved immediately. The postoperative course was
      normal. Neither of the patients had clinical signs of pelvic or systemic
      thromboembolism. CONCLUSION(S): Ultrasound-guided transvaginal ovarian cystic
      aspiration is a simple, safe, and effective method for the conservative
      management of adnexal torsion.

PMID- 17498707
TI  - Estrogen increases apoptosis in the arterial wall in a murine atherosclerosis
      model.
AB  - OBJECTIVE: To investigate the effect of estrogen (E) on vascular apoptosis during
      atherosclerotic plaque formation. DESIGN: Laboratory study using a murine
      atherosclerosis model. SETTING: Academic research center. ANIMAL(S): Female mice
      homozygous for null alleles of LDL receptor (LDL-R(-/-)) in a C57BL/6 background.
      LDL-R(-/-) mice develop atherosclerosis in a predictable manner when fed a high
      cholesterol diet. INTERVENTION(S): Eight-week-old female LDL-R(-/-) mice (n = 68)
      were ovariectomized, and implanted subcutaneously with 90-day release pellets
      containing 0.5 mg of 17beta-estradiol (E(2)) or placebo. Four animals were
      evaluated at the initiation of the study. Thereafter, four animals from each
      group were sacrificed weekly for 8 weeks and their aortas studied. MAIN OUTCOME
      MEASURE(S): The effect of E(2) on atherosclerotic plaque development, apoptosis,
      and cell proliferation was examined in the aorta of ovariectomized LDL-R(-/-)
      mice that were fed a high cholesterol diet. RESULT(S): Mice treated with E(2)
      displayed a delay in atherosclerotic plaque formation, associated with an
      increase in DNA strand breaks in the arterial wall indicative of increased
      apoptosis, compared to placebo-treated mice. The two groups did not differ in
      mitotic activity. CONCLUSION(S): In female LDL-R(-/-) mice fed a high cholesterol
      diet, ovariectomy is associated with increased atherogenesis. The effect of
      ovariectomy on atherogenesis is reversed by E(2) treatment. In addition to
      delayed atherogenesis, E(2) treatment of ovariectomized LDL-R(-/-) mice results
      in an increase in apoptosis in the aortic wall without an effect on the mitotic
      activity. Our findings suggest that vascular effects of E may be in part mediated
      by a proapoptotic activity.

PMID- 17498708
TI  - Does physicians' experience influence in vitro fertilization success in patients
      undergoing controlled ovarian hyperstimulation with GnRH antagonists?
AB  - In an attempt to examine whether physicians' experience may influence IVF outcome
      in patients undergoing GnRH antagonist (GnRH-a) controlled ovarian
      hyperstimulation (COH) protocols, we studied 273 consecutive patients, with a
      favorable prognosis a priori, admitted to our IVF unit, of whom 88 conceived. The
      highest pregnancy rate (PR) (46.5%) was observed in patients achieving, on day of
      hCG administration, an E(2)-to-follicle ratio <100 pg/mL. The timing of hCG
      administration is crucial in patients undergoing the GnRH-a COH for IVF to
      optimize success rate.

PMID- 17498709
TI  - Mucosal safety of PHI-443 and stampidine as a combination microbicide to prevent
      genital transmission of HIV-1.
AB  - OBJECTIVE: To investigate the in vitro and in vivo mucosal safety of a
      nonnucleoside reverse transcriptase (RT) inhibitor (PHI-443) and a nucleoside
      analogue RT inhibitor (stampidine)-based anti-HIV microbicide either alone or in
      combination. DESIGN: In vitro and in vivo studies using three-dimensional vaginal
      epithelia integrating Langerhans cells and 16 New Zealand White rabbits,
      respectively. SETTING: Research laboratory. INTERVENTION(S): Rabbits in groups of
      four were exposed intravaginally to a gel with and without 1% PHI-443, 1%
      stampidine, or 1% PHI-443 plus 1% stampidine for 14 days. Cytokine/chemokine
      release by three-dimensional co-cultures in the presence and absence of PHI-443
      or stampidine. MAIN OUTCOME MEASURES(S): Histologic scoring of vaginal tissue for
      mucosal toxicity at 24 hours after dosing. Simultaneous evaluation of levels of
      10 cytokines (granulocyte-macrophage colony-stimulating factor, interleukin-1
      alpha, interleukin-13, macrophage inflammatory protein-1 beta, granulocyte colony
      stimulating factor, interleukin-18, tumor necrosis factor-alpha, interleukin-6,
      interleukin-1 beta, and interferon-gamma) and 6 chemokines (epithelial neutrophil
      activating peptide-78, interleukin-8, monocyte/macrophage chemoattractant protein
      1, macrophage inflammatory protein-3 alpha, interferon-inducible protein-10, and
      regulated upon activation of normal T-cell expressed and secreted) in culture
      media by a multiplexed chemiluminescence-based immunoassay. RESULT(S): In the
      rabbit model, repeated intravaginal administration of PHI-443 plus stampidine via
      a gel formulation at concentrations nearly 2,000 and 10,000 times higher than
      their respective in vitro anti-HIV IC(50) values did not result in vaginal
      irritation. The levels of proinflammatory cytokines/chemokines secreted by
      multilayered human genital epithelia integrating Langerhans cells were unaffected
      by prolonged exposure to PHI-443 or stampidine. CONCLUSION(S): The combination of
      PHI-443 and stampidine was noncytotoxic to vaginal epithelial cells,
      nonirritating to vaginal mucosa, and did not induce the secretion of
      proinflammatory cytokines and chemokines by co-cultures of human genital
      epithelia and Langerhans cells. These attributes are particularly useful for the
      clinical development of PHI-443 and stampidine as a combination microbicide and
      as a prophylactic anti-HIV agent to curb genital transmission of HIV-1 by semen.

PMID- 17498710
TI  - Erectile dysfunction: does insulin resistance play a part?
AB  - OBJECTIVE: To review MEDLINE literature for correlations between insulin
      resistance and erectile dysfunction (ED). DESIGN: MEDLINE literature review (1966
      to present). SETTING: Academic medical center. PATIENT(S): None. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): None. RESULT(S): Erectile dysfunction affects more
      than half of men over the age of 40. Fortunately, most men with ED can be
      successfully treated with phosphodiesterase 5A (PDE-5) inhibitors, which up
      regulate the vasodilatory effects of nitric oxide (NO). Insulin resistance
      affects 25% of U.S. adults and increases to a 60% occurrence in individuals who
      are overweight. Endothelial dysfunction, which is associated with insulin
      resistance states, can cause disturbances in the subcellular signaling pathways
      required for NO production. Because endothelial production of NO and insulin
      sensitivity are positively related in healthy humans, the relationships among
      insulin resistance, NO, and ED are the target of this review of MEDLINE
      literature. CONCLUSION(S): Insulin resistance states are characterized by
      defective vascular NO production and impaired insulin-induced vasodilation, both
      of which are likely to cause ED. Diagnosing and treating insulin resistance
      should be part of the initial management plan for ED. Future studies concerning
      the cause and effect relationship of insulin resistance and ED should be
      implemented.

PMID- 17498711
TI  - Differences in characteristics among 1,000 women with endometriosis based on
      extent of disease.
AB  - OBJECTIVE: To determine the relationship between disease severity and patient
      characteristics in endometriosis. DESIGN: Cross-sectional study of self-reported
      survey data. SETTING: Academic research setting. PATIENT(S): One thousand women
      in the Oxford Endometriosis Gene (OXEGENE) study. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Participants were assigned to one of two groups with
      predominantly revised AFS stage I-II (group I, n = 423) or III-IV disease (group
      II, n = 517). Their characteristics were compared by disease extent. RESULT(S):
      Most participants were white (96%) and of reproductive age (81%). Women in group
      I were significantly younger on entering the study (39.9 +/- 0.5 vs. 44.5 +/- 0.4
      years). Overall time to diagnosis did not differ between groups. The most common
      symptoms leading to a diagnosis were dysmenorrhea (79%) and pelvic pain (69%). In
      group II, subfertility (21.5% vs. 30.0%) and an ovarian mass (7.3% vs. 29.4%)
      more commonly led to a diagnosis, whereas dyspareunia (51.1% vs. 39.5%) was
      significantly more common in group I. Subfertility (41.5% vs. 53.4%) remained
      more common in group II throughout reproductive life, although birth and
      miscarriage rates were similar. CONCLUSION(S): Pelvic pain is common to all with
      endometriosis and those with more extensive disease report higher rates of
      subfertility. Remarkably, the time to diagnosis was similar among women.

PMID- 17498712
TI  - Leiomyoma on the septum of a septate uterus with double cervix and vaginal
      septum: a challenge to manage.
AB  - OBJECTIVE: To describe the first case of a leiomyoma localized in the septum of a
      septate uterus that had cervical duplication and a longitudinal vaginal septum.
      DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 43-year-old
      patient with primary infertility and complaint of menorrhagia. INTERVENTION(S):
      Laparotomy, adhesiolysis, myomectomy, and resection of the vaginal septum in the
      first operation. Hysteroscopic resection of the complete uterine septum in the
      second operation. MAIN OUTCOME MEASURE(S): Magnetic resonance imaging findings
      and two-step repair of the anomaly. Cervical length at second trimester.
      RESULT(S): Restoration of normal anatomy was achieved after correct diagnosis and
      a two-step operation procedure. A normal cervical length was measured at 26 weeks
      of gestation. CONCLUSION(S): Large leiomyoma at rare localizations in the
      presence of uterine anomalies is a diagnostic challenge, but with available
      diagnostic technology and appropriate operations, successful results can be
      obtained.

PMID- 17498713
TI  - Preimplantation genetic diagnosis of X-linked adrenoleukodystrophy with gender
      determination using multiple displacement amplification.
AB  - OBJECTIVE: To evaluate the use of multiple displacement amplification (MDA) for
      whole genome amplification in the preimplantation genetic diagnosis (PGD) of X
      linked adrenoleukodystrophy. DESIGN: MDA was used to amplify the whole genome
      directly from a single blastomere. MDA products were used for polymerase chain
      reaction (PCR) analysis of two polymorphic markers flanking the ABCD1 gene and a
      new X/Y marker, X22, to sex embryos in an X-linked adrenoleukodystrophy PGD
      program. SETTING: Fertility and gynecology private center in Alicante, Spain.
      PATIENT(S): A couple in which the wife is a carrier of the ABCD1 gene mutation
      (676A-->C) that was previously identified in her family. INTERVENTION(S): MDA of
      single blastomere and PCR tests for PGD. MAIN OUTCOME MEASURE(S): The ability to
      analyze single blastomeres for X-linked adrenoleukodystrophy using MDA.
      RESULT(S): The development of an MDA-PGD protocol for X-linked
      adrenoleukodystrophy allowed for the diagnosis of five embryos. These were
      biopsied on day 3 of culture and analyzed. One embryo was an affected male and
      one embryo was a female carrier. Three healthy female embryos were transferred 48
      hours after biopsy. Unfortunately, no pregnancy was achieved. CONCLUSION(S): The
      MDA technique is useful for overcoming the problem of insufficient genomic DNA in
      PGD and allows the simultaneous amplification of different targets to perform a
      diagnosis of any known gene defect and a sexing test by standard methods and
      conditions.

PMID- 17498715
TI  - Corticosterone administration does not affect timing of breeding in Florida scrub
      jays (Aphelocoma coerulescens).
AB  - Providing supplemental food to Florida scrub-jays (Aphelocoma coerulescens)
      causes a reliable advance in clutch initiation of 1 to 2 weeks. In some years,
      supplemental food appeared to not only advance laying date but also decrease
      baseline concentrations of corticosterone (CORT) relative to controls. The
      coincidence of low CORT levels and early breeding led us to hypothesize that CORT
      serves to communicate information about environmental conditions to the
      hypothalamic-pituitary-gonadal (HPG) axis, which ultimately influences the timing
      of breeding. To test this hypothesis, we administered small oral doses of CORT
      three times each day to female breeders that were provisioned with supplemental
      food. We compared clutch initiation dates of the CORT-dosed females to females
      with supplementation but no exogenous CORT and to females with neither CORT nor
      supplemental food. CORT administration had a strong temporary effect on
      circulating CORT concentrations but clutch initiation did not differ between the
      two groups of supplemented birds, both of which laid eggs approximately 10 days
      earlier than nonsupplemented birds. Furthermore, during the year of our study we
      found no reduction in baseline CORT concentrations in our undosed supplemental
      groups, as had been observed in past studies.

PMID- 17498714
TI  - PPAR-gamma receptor ligand induces regression of endometrial explants in baboons:
      a prospective, randomized, placebo- and drug-controlled study.
AB  - OBJECTIVE: To determine the effects of a thiazolidinedione (TZD) agonist of
      peroxisome proliferator-activated receptor (PPAR)-gamma, rosiglitazone, in a
      baboon model of established endometriosis. DESIGN: Prospective, randomized,
      placebo-controlled study. SETTING: Experimental surgery laboratory at the
      Institute of Primate Research in Nairobi, Kenya. ANIMAL(S): Endometriosis was
      induced using intrapelvic injection of eutopic menstrual endometrium in 12 female
      baboons with a normal pelvis that had undergone at least one menstrual cycle
      since the time of captivity. INTERVENTION(S): Induction of endometriosis by
      laparoscopy was performed in 12 baboons with a normal pelvis. Endometrial tissue
      was extracted from each baboon by curettage, and a standard amount of endometrium
      was then seeded onto several peritoneal sites. About 34-68 days after the
      induction of laparoscopy, a pretreatment laparoscopy (baseline disease
      assessment) was performed in the baboons to record the extent of endometriotic
      lesions. The 12 baboons were randomized into three groups and treated from the
      day after the staging laparoscopy for a total duration of 30 days. They received
      phosphate-buffered saline tablets (n = 4, placebo control; placebo tablets once a
      day by mouth for 30 days), GnRH-antagonists (n = 4, active control; ganirelix
      acetate 125 microg/day for 30 days), or rosiglitazone (n = 4, test drug, 2 mg by
      mouth each day for 30 days). A third and final laparoscopy on day 30 after the
      start of treatment was performed to record the extent of endometriosis. The type
      of lesion (typical, red, white, or suspicious) was recorded. Biopsies were
      obtained to confirm the histological presence of endometriosis. MAIN OUTCOME
      MEASURE(S): A videolaparoscopy was performed 30 days after treatment to document
      the number and surface area of endometriotic lesions as well as to calculate the
      revised American Society for Reproductive Medicine score and stage. RESULT(S):
      The surface area of endometriotic lesions was statistically significantly lower
      in rosiglitazone-treated baboons when compared with the placebo group. Baboons
      treated with rosiglitazone or ganirelix had a greater negative relative change in
      surface area of peritoneal endometriotic lesions than controls. The overall
      weighted appearance of the lesion types suggests that rosiglitazone may deter the
      development of newer endometriotic lesions. CONCLUSION(S): A PPAR-gamma ligand,
      rosiglitazone, effectively diminishes the burden of endometriosis disease in a
      baboon endometriosis model. This animal model holds promise that a TZD drug may
      be helpful in women with endometriosis.

PMID- 17498716
TI  - Inferior vena cava filter thrombo-prophylaxis in high-risk twin pregnancy.

PMID- 17498717
TI  - Calpain-dependent calpastatin cleavage regulates caspase-3 activation during
      apoptosis of Jurkat T cells induced by Entamoeba histolytica.
AB  - In this study, we investigated whether there is a signalling interaction between
      calpain and caspase-3 during apoptosis in Jurkat T cells by Entamoeba
      histolytica. When Jurkat cells were co-incubated with E. histolytica,
      phosphatidylserine externalisation and DNA fragmentation markedly increased
      compared with results for cells incubated with medium alone. In addition, E.
      histolytica strongly induced cleavage of caspases-3, -6, -7 and poly(ADP-ribose)
      polymerase. A rise in intracellular calcium levels and activation of calpain were
      seen in Jurkat cells after exposure to E. histolytica. Pretreatment of Jurkat
      cells with calpain inhibitor calpeptin effectively blocked E. histolytica
      triggered cleavage of caspase-3 as well as calpain. In contrast, pan-caspase
      inhibitor did not affect E. histolytica-induced calpain activation. In addition,
      incubation with E. histolytica resulted in multiple fragmented bands of
      calpastatin, which is an endogenous inhibitor of calpain, in Jurkat T cells.
      Moreover, Entamoeba-induced calpastatin degradation was dramatically suppressed
      by pretreatment with calpeptin, but not by z-VAD-fmk. Entamoeba-induced DNA
      fragmentation was strongly retarded by z-VAD-fmk, but not calpeptin. Our results
      suggest that calpain-mediated calpastatin degradation plays a crucial role in
      regulation of caspase-3 activation during apoptosis of Jurkat T cells by E.
      histolytica.

PMID- 17498718
TI  - The increase in human plasma antioxidant capacity after red wine consumption is
      due to both plasma urate and wine polyphenols.
AB  - By using red wine, dealcoholized red wine, polyphenols-stripped red wine, ethanol
      water solution and water, the role of wine polyphenols and induction of plasma
      urate elevation on plasma antioxidant capacity was examined in humans (n=9 per
      beverage). Healthy males randomly consumed each beverage in a cross-over design.
      Plasma antioxidant capacity (measured by ferric reducing antioxidant power,
      FRAP), ethanol, catechin and urate concentrations were determined before and 30,
      60, 90, 120 and 180 min after beverage intake. Dealcoholized red wine and
      polyphenols-stripped red wine induced similar increase in FRAP values which
      represented nearly half the effect of the original red wine. This indicates that
      consumption of red wine involves two separate mechanisms in elevation of plasma
      FRAP values and both wine phenols and plasma urate contribute to that effect.

PMID- 17498719
TI  - Complement system is activated in stenotic aortic valves.
AB  - OBJECTIVE: To examine the role of the complement system, a source of powerful
      proinflammatory mediators, in aortic valve stenosis (AS). METHODS AND RESULTS:
      Stenotic aortic valves (n=24) were obtained at valve replacement surgery, and non
      stenotic (n=12) and early sclerotic (n=4) valves at cardiac transplantations. The
      terminal complement complex C5b-9 was stained by immunohistochemistry. Expression
      of the anaphylatoxin receptors C3aR and C5aR was studied in the valves by
      immunohistochemistry and RT-PCR, and in isolated valve myofibroblasts after
      stimulation with potential AS-accelerating factors (TNF-alpha and cigarette
      smoke) by RT-PCR. Cultured myofibroblasts were exposed to C3a, and their
      secretion of proinflammatory cytokines was assessed by ELISA. C5b-9 was found
      already in early aortic valve lesions, and its deposition was augmented in
      advanced stenotic valves. In stenotic valves, expression of C3aR mRNA was
      upregulated (p<0.05) and strong staining of C3aR and C5aR was detected.
      Myofibroblasts in stenotic, but not in control valves, expressed C3aR, and, in
      isolated myofibroblasts, TNF-alpha and cigarette smoke induced C3aR mRNA
      expression (p<0.05 for both). Stimulation of myofibroblasts with C3a resulted in
      enhanced secretion of MCP-1 (p<0.001), IL-6 (p=0.003), and IL-8 (p=0.03).
      CONCLUSIONS: In stenotic aortic valves, complement is activated leading to
      generation of the anaphylatoxins C3a and C5a. Upregulation of C3aR in the valves
      as a result of inflammation and external risk factors, such as cigarette smoke,
      leads to an inflammatory response in aortic valve myofibroblasts. Complement
      activation in stenotic valves emerges as a novel pathogenic component of AS and
      may serve as a therapeutic target in this disease.

PMID- 17498720
TI  - Stationary phase optimized selectivity liquid chromatography: Basic possibilities
      of serially connected columns using the "PRISMA" principle.
AB  - A new procedure (stationary phase optimized selectivity liquid chromatography:
      SOS-LC) is described for the optimization of the HPLC stationary phase, using
      serially connected columns and the principle of the "PRISMA" model. The retention
      factors (k) of the analytes were determined on three different stationary phases.
      By use of these data the k values were predicted applying theoretically combined
      stationary phases. These predictions resulted in numerous intermediate
      theoretical separations from among which only the optimal one was assembled and
      tested. The overall selectivity of this separation was better than that of any
      individual base stationary phase. SOS-LC is independent of the mechanism and the
      scale of separation.

PMID- 17498721
TI  - Multiresponse optimization and parallel factor analysis, useful tools in the
      determination of estrogens by gas chromatography-mass spectrometry.
AB  - This paper reports an experimental design optimization of a recently proposed
      silylation procedure that avoids the introduction of false positives and false
      negatives in the simultaneous determination of steroid hormone estrone (E1) and
      17-alpha-ethinylestradiol (EE2) by gas chromatography-mass spectrometry (GC/MS).
      The figures of merit for several calibration procedures were evaluated under
      optimum conditions in the silylation step. Internal standardization strategies
      were applied and global models were constructed by gathering signals recorded on
      three non-consecutive days. Three calibration models were examined: a univariate
      model with a sum of six monitorized ions and a three-way PARAFAC-based model (the
      analyte scores were standardized on the basis of the scores of the internal
      standard). The global PARAFAC-based calibration model showed the best performance
      with detection capabilities of 4.3 microg l(-1) and 7.0 microg l(-1) for E1 and
      EE2, respectively, when the probability of false positives was fixed at 1% and
      that of false negatives at 5%. Mean relative error in absolute terms for E1 and
      for EE2 was 11.1% and 8.5%, respectively, and trueness was likewise confirmed.
      The proposed optimized derivatization procedure using a three-way calibration
      function was also applied in the determination of E1, 17-beta-estradiol (E2) and
      EE2 in bovine urine samples: recovery values were 68.5%, 40.4% and 43.4%,
      respectively, and the detection capability was 18.4, 19.3 and 18.6 microg l(-1)
      when the probability of false positives was fixed at 1% and that of false
      negatives at 5%. Mean relative error in absolute terms for E1, E2 and EE2 was
      7.4%, 9.4% and 8.6%, respectively, and trueness was likewise confirmed.

PMID- 17498723
TI  - Simple algorithms for fitting and optimisation for multilinear gradient elution
      in reversed-phase liquid chromatography.
AB  - The theory of the multilinear gradient elution in reversed-phase liquid
      chromatography (RP-HPLC) presented in [P. Nikitas, A. Pappa-Louisi, P.
      Agrafiotou, J. Chromatogr. A 1120 (2006) 299] is modified to increase its
      flexibility. In addition, it is embodied to simple algorithms for fitting
      gradient data and especially for resolution optimisation under multilinear
      gradient conditions. In particular, two new algorithms for fitting and one for
      optimisation are tested and compared with conventional algorithms. Their
      performance was examined using 13 o-phthalaldehyde (OPA) derivatives of amino
      acids with mobile phases modified by acetonitrile. It was found that the new
      proposed algorithms, a repeated application of the Levenberg-Marquardt (LM)
      method for fitting (R_LM) and a modified descent algorithm for optimisation
      (RND_D), in combination with the modified theory of the multilinear gradient
      elution can lead to high quality predictions of the retention times and
      optimisation results.

PMID- 17498724
TI  - Rational method for designing efficient separations by chromatography on
      polystyrene-divinylbenzene resins eluted with aqueous ethanol.
AB  - A rational method for designing separation processes by chromatography with
      polystyrene-divinylbenzene (PS-DVB) resins of different particle diameters (10
      400microm) was developed. As model samples, catechin and epigallocatehin gallate
      (EGCG) were chosen and the mobile phase was an ethanol-water mixture. Linear
      gradient elution experiments were carried out with different gradient slopes, and
      the peak ethanol concentration was plotted against the normalized gradient slope.
      The plots were similar regardless of particle diameter. From these plots the two
      parameters describing the distribution coefficient K as a function of ethanol
      concentration I were determined. The K-I curves obtained were verified by
      isocratic elution experiments, and the conditions at which a baseline separation
      of the two polyphenols is possible was sought, and confirmed experimentally.
      Stepwise elution experiments were also designed and performed successfully on the
      basis of the K-I curve.

PMID- 17498725
TI  - Total pore blocking as an alternative method for the on-column determination of
      the external porosity of packed and monolithic reversed-phase columns.
AB  - An alternative method to determine the interstitial void volume and the external
      porosity inside a packed or a monolithic column was developed. The method is
      based on the total blocking of the mesopores of a porous support by filling them
      with a hydrophobic solvent. The strong interaction of the latter with the
      hydrophobic coating inside the pores keeps the solvent in position during the
      subsequent measurements. With the pores of the stationary phase material
      completely inaccessible for any type of polar molecules, the method allows to
      perform interstitial void measurements using small molecular weight (MW)
      molecules instead of the large MW molecules that need to be used in inverse size
      exclusion chromatography (ISEC). These small MW molecules are able to penetrate
      every corner of the interstitial volume and therefore lead to a very accurate
      determination of the external porosity. Since only one type of molecules needs to
      be injected, the often troublesome regression analysis needed in ISEC is omitted
      as well. In the present contribution, the method has been applied to a packed bed
      and a monolithic column to investigate the optimal conditions of flow velocity,
      liquid compositions, and unretained marker selection. The robustness and the
      repeatability of the method are discussed as well.

PMID- 17498726
TI  - High-performance liquid chromatography and nuclear magnetic resonance study of
      linear tetrapeptides and octapeptides containing N-methylated amino acid
      residues.
AB  - Chromatographic behavior of a series of N-methylated tetra and octapeptides on a
      reversed-phase sorbent was studied considering the information obtained on these
      compounds by NMR spectroscopy. The modified tetrapeptides were derived from GFFY
      NH2, GFFF-NH2 and GFFH-NH2 primary structures by N-methylation at various peptide
      bond positions. Similarly, the N-methylated octapeptides were based on TPK(Pac)T
      C-terminally elongated forms of GFFY and GFFF. It was found that many studied N
      methylated peptides provide broad peaks as a consequence of cis/trans isomerism
      of the R1CON(CH3)R2 peptide bond. The extent of the peak spreading depends on the
      following important factors: the nature of the surrounding amino acid residues,
      the location of the modified peptide bond within the peptide chain, temperature,
      and mobile phase flow-rate. All these aspects were critically evaluated. Nearly
      complete separation of the individual conformers of GF(NMe)FY-NH2 was obtained
      applying fast chromatography on short column packed with 20-30 microm reversed
      phase sorbent.

PMID- 17498727
TI  - Capillary electrophoresis with end-column electrochemiluminescence for the
      analysis of chloroquine phosphate and the study on its interaction with human
      serum albumin.
AB  - This paper describes a novel and sensitive method for the estimation of
      chloroquine phosphate (CQ) using capillary electrophoresis with end-column
      electrochemiluminescence (ECL) detection. Under the optimized condition, linear
      calibration curve was obtained for the system over two orders of magnitude with a
      detection limit of 3x10(-7) M (S/N=3). The relative standard deviations of the
      ECL intensity and the migration time were 1.4% and 0.05%, respectively (n=6,
      5x10(-5) M CQ). Successful separation of chloroquine phosphate, difenidol
      hydrochloride and clomifene citrate was obtained at pH 7.0. Using the proposed
      electrochemiluminescence system, a simple method was proposed to study the
      interaction between chloroquine phosphate and human serum albumin (HSA), and the
      number of binding sites and binding constant were estimated to be 32.6 and
      7.7x10(3) M(-1), respectively.

PMID- 17498728
TI  - Adsorption characteristics of nanoporous carbon-silica composites synthesized
      from graphite oxide by a mechanochemical intercalation method.
AB  - Nanoporous carbon-silica composites were synthesized from graphite oxide (GO)
      precursor by a mechanochemical intercalation (MCI) method at different
      conditions, and their structural property, thermal decomposition behaviors, and
      adsorption characteristics were examined. MCI method yields regular
      tetraethoxysilane (TEOS)-intercalated GO layer structures with controllable
      silicon content depending on the TEOS addition. Adsorption behaviors of water and
      hexane indicate the amphiphilic properties of the composites. The detailed
      porosities of the composites and their changes upon water adsorption were
      analyzed on the basis of alpha(s)-plot method of N(2) adsorption isotherms using
      a weight-averaged standard data from non-porous silica and non-porous carbon,
      which plausibly divides microporosity and mesoporosity.

PMID- 17498729
TI  - Synthesis and physicochemical characterization of a novel ampholytic pullulan
      derivative with amphiphilic behavior in alkaline media.
AB  - Pullulan derivative was synthesized by coupling carboxymethylpullulan (degree of
      substitution DS(0)(in)=0.7) and dimethylaminopropylamine (DMAPA), activated by a
      hydrosoluble carbodiimide N(')-(3-dimethylaminopropyl)-N-ethylcarbodiimide
      hydrochloride (EDAC). FTIR and (13)C and (1)H NMR spectroscopic analyses have
      evidenced that the polysaccharide has been successfully modified. (1)H NMR,
      nitrogen analysis, and conductimetric measurements allow determination of the
      degree of substitution in both carboxylic acid and amine functions. We have found
      that both functions present a similar DS of 0.35, which is characteristic of an
      ampholytic polymer with possible zwitterionic-type properties. Solution
      properties have been studied by flow field flow fractionation (F4) coupled on
      line with multiangle laser light scattering (MALLS) and quasi elastic light
      scattering (QELS), surface tension, and viscosity measurements. The behavior has
      been found largely pH dependent and an amphiphilic behavior has been evidenced in
      alkaline media.

PMID- 17498730
TI  - Self-assembled monolayers: influence of complementarity between chemisorbed and
      crystallizing molecules in polymorph selection.
AB  - The role of self-assembled monolayers in dictating the arrangement of molecules
      at the interface in a developing solid is explored. A self-assembled monolayer
      incorporating a complementary backbone structure between chemisorbed and
      crystallizing molecules of 4-hydroxybiphenyl favors its crystallization in a new
      monoclinic crystal packing arrangement.

PMID- 17498731
TI  - Controlled synthesis of alpha-Fe2O3 nanorods and its size-dependent optical
      absorption, electrochemical, and magnetic properties.
AB  - Uniform alpha-Fe(2)O(3) nanorods with diameter of about 30 nm and length up to
      500 nm were synthesized by a template-free hydrothermal method and a following
      calcination of the intermediate product in the air at 500 degrees C for 2 h. By
      carefully tuning the concentration of the reactants, a series of alpha-Fe(2)O(3)
      nanorods with gradient in aspect ratios can be obtained. The effect of the
      solvent was also evaluated. Based on the experimental facts, the formation
      mechanism of this one-dimensional structure was proposed. The size-dependent
      properties of the as-obtained alpha-Fe(2)O(3) nanorods were investigated. The
      optical absorption properties of the samples showed that the band gaps of the
      samples decreased in the sequence in which the size increased. The
      electrochemical performance of the samples showed that the discharge capacity
      decreased as the size of the sample increased, which may result from the high
      surface area and small size. The magnetic hysteresis measurements taken at 5 K
      showed that the coercivities of the samples were related to the aspect ratios of
      the samples, which may result from the larger shape anisotropy. However, the
      temperature-dependent field cooling magnetization showed that there was no Morin
      transition in the as-prepared samples, which may result from the surface effect.

PMID- 17498732
TI  - Polistes dominulus (Hymenoptera: Vespidae) larvae possess their own chemical
      signatures.
AB  - Social insects use cuticular hydrocarbons (CHCs) as recognition cues in a variety
      of social contexts, such as species and nestmate recognition. Discrimination of
      nestmates is an important requisite to avoid exploitation by unrelated
      individuals. In social wasps, use of CHCs in nestmate recognition has been
      demonstrated only among adults, whereas very little is known regarding brood
      recognition. We performed gas chromatography-mass spectrometry analyses of the
      CHCs of adults and larvae of the social wasp Polistes dominulus and found that
      larvae possess a characteristic chemical colony-specific pattern distinct from
      that of adults. Behavioural assays confirmed that these are recognized and
      discriminated by adults. Larval epicuticular substances are therefore sufficient
      for recognition of nestmate larvae by adults and demonstrate that wasps are able
      to discriminate between alien and nestmate larval odours.

PMID- 17498733
TI  - Molecular aspects of transferrin expression in the tsetse fly (Glossina morsitans
      morsitans).
AB  - Iron is an essential element for metabolic processes intrinsic to life, and yet
      the properties that make iron a necessity also make it potentially deleterious.
      To avoid harm, iron homeostasis is achieved via proteins involved in transport
      and storage of iron, one of which is transferrin. We describe the temporal and
      spatial aspects of transferrin (GmmTsf) expression and its transcriptional
      regulation in tsetse where both the male and female are strictly hematophagous.
      Using Northern, Western and immunohistochemical analysis, we show that GmmTsf is
      abundant in the hemolymph and is expressed in the adult developmental stages of
      male and female insects. It is preferentially expressed in the female milk gland
      tubules and its expression appears to be cyclical and possibly regulated in
      synchrony with the oogenic and/or larvigenic cycle. Although no mRNA is detected,
      GmmTsf protein is present in the immature stages of development, apparently being
      transported into the intrauterine larva from the mother via the milk gland ducts.
      Transferrin is also detected in the vitellogenic ovary and the adult male testes,
      further supporting its classification as a vitellogenic protein. Similar to
      reports in other insects, transferrin mRNA levels increase upon bacterial
      challenge in tsetse suggesting that transferrin may play an additional role in
      immunity. Although transferrin expression is induced following bacterial
      challenge, it is significantly reduced in tsetse carrying midgut trypanosome
      infections. Analysis of tsetse that have cured the parasite challenge shows
      normal levels of GmmTsf. This observation suggests that the parasite in competing
      for the availability of limited dietary iron may manipulate host gene expression.

PMID- 17498734
TI  - Cardiac IK1 underlies early action potential shortening during hypoxia in the
      mouse heart.
AB  - It is established that prolonged hypoxia leads to activation of K(ATP) channels
      and action potential (AP) shortening, but the mechanisms behind the early phase
      of metabolic stress remain controversial. Under normal conditions IK1 channels
      are constitutively active while K(ATP) channels are closed. Therefore, early
      changes in IK1 may underlie early AP shortening. This hypothesis was tested using
      transgenic mice with suppressed IK1 (AAA-TG). In isolated AAA-TG hearts AP
      shortening was delayed by approximately 24 s compared to WT hearts. In WT
      ventricular myocytes, blocking oxidative phosphorylation with 1 mM cyanide (CN;
      28 degrees C) led to a 29% decrease in APD90 within approximately 3-5 min. The
      effect of CN was reversed by application of 100 microM Ba2+, a selective blocker
      of IK1, but not by 10 microM glybenclamide, a selective blocker of KATP channels.
      Accordingly, voltage-clamp experiments revealed that both CN and true hypoxia
      lead to early activation of IK1. In AAA-TG myocytes, neither CN nor glybenclamide
      or Ba2+ had any effect on AP. Further experiments showed that buffering of
      intracellular Ca2+ with 20 mM BAPTA prevented IK1 activation by CN, although CN
      still caused a 54% increase in IK1 in a Ca2+ -free bath solution. Importantly,
      both (i) 20 microM ruthenium red, a selective inhibitor of SR Ca2+ -release, and
      (ii) depleting SR by application of 10 microM ryanodine+1 mM caffeine, abolished
      the activation of IK1 by CN. The above data strongly argue that in the mouse
      heart IK1, not KATP, channels are responsible for the early AP shortening during
      hypoxia.

PMID- 17498735
TI  - Transcription factors Csx/Nkx2.5 and GATA4 distinctly regulate expression of Ca2+
      channels in neonatal rat heart.
AB  - The cardiac transcription factors Csx/Nkx2.5 and GATA4 play important roles in
      vertebrate heart development. Although mutations of Csx/Nkx2.5 or GATA4 are
      associated with various congenital heart diseases, their mechanism of action on
      cardiomyocyte function is not completely elucidated. In this study, we therefore
      investigated the actions of these transcription factors on the
      electrophysiological features and expression of ion channels in cardiomyocytes.
      Genes for transcription factors Csx/Nkx2.5 and GATA4 were transfected into rat
      neonatal cardiomyocytes by adenoviral infection. Action potentials, L-, T-type
      Ca(2+) channels and hyperpolarization-activated cation current (I(h)) of rat
      neonatal myocytes were recorded by patch clamp technique after adenoviral
      infection. Expression of ion channels was confirmed by real-time PCR. In
      Csx/Nkx2.5 overexpression myocytes, the spontaneous beating rate was markedly
      increased with an up-regulation of the Ca(v)3.2 T-type Ca(2+) channel, while in
      GATA4 overexpression myocytes, the T-type Ca(2+) channel was unchanged. On the
      other hand, the L-type Ca(2+) channel was down-regulated by both Csx/Nkx2.5 and
      GATA4 overexpression; the level of Ca(v)1.3 mRNA was dramatically decreased by
      Csx/Nkx2.5 overexpression. These results indicate that Csx/Nkx2.5 and GATA4 play
      important roles on the generation of pacemaker potentials modulating voltage
      dependent Ca(2+) channels in the neonatal cardiomyocyte.

PMID- 17498736
TI  - Expression of microRNAs is dynamically regulated during cardiomyocyte
      hypertrophy.
AB  - MicroRNAs (miRNAs) are a recently discovered class of approximately 22-nucleotide
      regulatory RNAs that post-transcriptionally regulate gene expression. We have
      recently demonstrated that muscle-specific miRNAs miR-1 and miR-133 play an
      important role in modulating muscle proliferation and differentiation. Here, we
      investigate the involvement of miRNAs in cardiac hypertrophy. We analyzed the
      global expression of miRNAs in agonist-induced hypertrophic cardiomyocytes as
      well as in pressure overload-induced hypertrophic hearts and found the miRNA
      expression profile altered in those hypertrophic conditions. We further show that
      inhibition of endogenous miR-21 or miR-18b augments hypertrophic growth.
      Conversely, introduction of functional miR-21 or miR-18b into cardiomyocytes
      represses myocyte hypertrophy. Together, our studies point to miRNAs as critical
      regulators of cardiac hypertrophy.

PMID- 17498737
TI  - HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects
      cardiomyocytes against ischemia.
AB  - Hypoxia inducible factor-1alpha (HIF-1alpha) is a proangiogenic transcription
      factor stabilized and activated under hypoxia. It regulates the expression of
      numerous target genes, including vascular endothelial growth factor (VEGF) and
      other cytoprotective proteins. In this study, we hypothesized that bone marrow
      stem cells (BMSCs) secrete growth factors which protect cardiomyocytes via HIF
      1alpha pathway. BMSCs were obtained from transgenic mice overexpressing green
      fluorescent protein (GFP). The study was carried out in vitro using co-culture of
      BMSCs with cardiomyocytes. LDH release, MTT uptake, DNA fragmentation and annexin
      V positive cells were used as cell injury markers. The level of HIF-1alpha
      protein as well as its activated form and VEGF were measured by ELISA. The
      expression of HIF-1alpha and VEGF in BMSCs was analyzed by quantitative PCR and
      cellular localization was determined by immunohistochemistry. LDH release was
      increased and MTT uptake was decreased after exposure of cardiomyocytes to
      hypoxia for 30 h, which were prevented by co-culturing cardiomyocytes with BMSCs.
      Cardiomyocyte apoptosis induced by hypoxia and H(2)O(2) was also reduced by co
      culture with BMSCs. VEGF release from BMSCs was significantly increased in
      parallel with high level of HIF-1alpha in BMSCs following anoxia or hypoxia in a
      time-dependent manner. Although no significant up-regulation could be seen in HIF
      1alpha mRNA, HIF-1alpha protein and its activated form were markedly increased
      and translocated to the nucleus or peri-nuclear area. The increase and
      translocation of HIF-1alpha in BMSCs were completely blocked by 2
      methoxyestradiol (2-ME2; 5 mumol), a HIF-1alpha inhibitor. Moreover, the
      protection of cardiomyocytes by BMSC and VEGF secretion was abolished by
      neutralizing HIF-1alpha antibody in a concentration dependent manner (200-3200
      ng/ml). Bone marrow stem cells protect cardiomyocytes by up-regulation of VEGF
      via activating HIF-1alpha.

PMID- 17498738
TI  - Structure of calcineurin in complex with PVIVIT peptide: portrait of a low
      affinity signalling interaction.
AB  - The protein phosphatase calcineurin recognizes a wide assortment of substrates
      and controls diverse developmental and physiological pathways in eukaryotic
      cells. Dephosphorylation of the transcription factor NFAT and certain other
      calcineurin substrates depends on docking of calcineurin at a PxIxIT consensus
      site. We describe here the structural basis for recognition of the PxIxIT
      sequence by calcineurin. We demonstrate that the high-affinity peptide ligand
      PVIVIT adds as a beta-strand to the edge of a beta-sheet of calcineurin; that
      short peptide segments containing the PxIxIT consensus sequence suffice for
      calcineurin-substrate docking; and that sequence variations within the PxIxIT
      core modulate the K(d) of the interaction within the physiological range 1 microM
      to 1 mM. Calcineurin can adapt to a wide variety of substrates, because
      recognition requires only a PxIxIT sequence and because variation within the core
      PxIxIT sequence can fine-tune the affinity to match the physiological signalling
      requirements of individual substrates.

PMID- 17498740
TI  - Modelling transcriptional interference and DNA looping in gene regulation.
AB  - We describe a hybrid statistical mechanical and dynamical approach for modelling
      the formation of closed, open and elongating complexes of RNA polymerase, the
      interactions of these polymerases to produce transcriptional interference, and
      the regulation of these processes by a DNA-binding and DNA-looping regulatory
      protein. As a model system, we have used bacteriophage 186, for which genetic,
      biochemical and structural studies have suggested that the CI repressor binds as
      a 14-mer to form alternative DNA-looped complexes, and activates lysogenic
      transcription indirectly by relieving transcriptional interference caused by the
      convergent lytic promoter. The modelling showed that the original mechanisms
      proposed to explain this relief of transcriptional interference are not
      consistent with the available in vivo reporter data. However, a good fit to the
      reporter data was given by a revised model that incorporates a novel predicted
      regulatory mechanism: that RNA polymerase bound at the lysogenic promoter
      protects itself from transcriptional interference by recruiting CI to the lytic
      promoter. This mechanism and various estimates of in vivo biochemical parameters
      for the 186 CI system should be testable. Our results demonstrate the power of
      mathematical modelling for the extraction of detailed biochemical information
      from in vivo data.

PMID- 17498739
TI  - Distinctive topologies of partner-switching signaling networks correlate with
      their physiological roles.
AB  - Regulatory networks controlling bacterial gene expression often evolve from
      common origins and share homologous proteins and similar network motifs. However,
      when functioning in different physiological contexts, these motifs may be re
      arranged with different topologies that significantly affect network performance.
      Here we analyze two related signaling networks in the bacterium Bacillus subtilis
      in order to assess the consequences of their different topologies, with the aim
      of formulating design principles applicable to other systems. These two networks
      control the activities of the general stress response factor sigma(B) and the
      first sporulation-specific factor sigma(F). Both networks have at their core a
      "partner-switching" mechanism, in which an anti-sigma factor forms alternate
      complexes either with the sigma factor, holding it inactive, or with an anti-anti
      sigma factor, thereby freeing sigma. However, clear differences in network
      structure are apparent: the anti-sigma factor for sigma(F) forms a long-lived,
      "dead-end" complex with its anti-anti-sigma factor and ADP, whereas the genes
      encoding sigma(B) and its network partners lie in a sigma(B)-controlled operon,
      resulting in positive and negative feedback loops. We constructed mathematical
      models of both networks and examined which features were critical for the
      performance of each design. The sigma(F) model predicts that the self-enhancing
      formation of the dead-end complex transforms the network into a largely
      irreversible hysteretic switch; the simulations reported here also demonstrate
      that hysteresis and slow turn off kinetics are the only two system properties
      associated with this complex formation. By contrast, the sigma(B) model predicts
      that the positive and negative feedback loops produce graded, reversible behavior
      with high regulatory capacity and fast response time. Our models demonstrate how
      alterations in network design result in different system properties that
      correlate with regulatory demands. These design principles agree with the known
      or suspected roles of similar networks in diverse bacteria.

PMID- 17498741
TI  - The structural basis for the exo-mode of action in GH74 oligoxyloglucan reducing
      end-specific cellobiohydrolase.
AB  - Oligoxyloglucan reducing end-specific cellobiohydrolase (OXG-RCBH) is a unique
      exo-beta-1,4-glucanase that belongs to glycoside hydrolase family 74. The enzyme
      recognizes the reducing end of xyloglucan oligosaccharides and releases two
      glucosyl residue segments from the reducing end of the main chain. Previously, we
      reported that OXG-RCBH consists of two seven-bladed beta-propeller domains. There
      is a large cleft between the two domains, and a unique loop encloses one side of
      the active site cleft. Here, we report the X-ray crystal structure of the OXG
      RCBH-substrate complex determined to a resolution of 2.4 A. The substrate bound
      to the cleft, and its reducing end was arranged near the loop region that is
      believed to impart OXG-RCBH with its activity. We constructed a deletion mutant
      of the loop region and conducted a detailed analysis. A deletion mutant of the
      loop region showed endo-activity with altered substrate recognition. More
      specifically, cleavage occurred randomly instead of at specific sites, most
      likely due to the misalignment of the substrate within the subsite. We believe
      that the loop imparts unique substrate specificity with exo-mode hydrolysis in
      OXG-RCBH.

PMID- 17498742
TI  - The role of high affinity non-specific DNA binding by Lrp in transcriptional
      regulation and DNA organization.
AB  - Transcriptional regulatory proteins typically bind specific DNA sequences with
      approximately 10(3)-10(7)-fold higher affinity than non-specific DNA and this
      discrimination is essential for their in vivo function. Here we show that the
      bacterial leucine-responsive regulatory protein (Lrp) does not follow this trend
      and has a approximately 20-400-fold binding discrimination between specific and
      non-specific DNA sequences. We suggest that the dual function of Lrp to regulate
      genes and to organize DNA utilizes this unique property. A approximately 20-fold
      decrease in binding affinity from specific DNA is dependent upon cryptic binding
      sites, including the sequence GN(2-3)TTT and A-tracts. Removal of these sites
      still results in high binding affinity, only approximately 70-fold weaker than
      that of specific sites. Similar to Lrp's binding of specific sites in the pap and
      ilvIH promoters, Lrp binds cooperatively to non-specific DNA; thus,
      protein/protein interactions are important for both specific and non-specific DNA
      binding. When considering this cooperativity of Lrp binding, the binding
      selectivity to specific sites may increase to a maximum of approximately 400
      fold. Neither leucine nor the pap-specific local regulator PapI alter Lrp's non
      specific binding affinity or cooperative binding of non-specific DNA. We
      hypothesize that Lrp combines low sequence discrimination and relatively high
      intracellular protein concentrations to ensure its ability to regulate the
      transcription of specific genes while also functioning as a nucleoid-associated
      protein. Modeling of Lrp binding data and comparison to other proteins with
      regulatory and nucleoid-associated properties suggests similar mechanisms.

PMID- 17498743
TI  - Structure of the cytochrome b6f complex: quinone analogue inhibitors as ligands
      of heme cn.
AB  - A native structure of the cytochrome b(6)f complex with improved resolution was
      obtained from crystals of the complex grown in the presence of divalent cadmium.
      Two Cd(2+) binding sites with different occupancy were determined: (i) a higher
      affinity site, Cd1, which bridges His143 of cytochrome f and the acidic residue,
      Glu75, of cyt b(6); in addition, Cd1 is coordinated by 1-2 H(2)O or 1-2 Cl(-);
      (ii) a second site, Cd2, of lower affinity for which three identified ligands are
      Asp58 (subunit IV), Glu3 (PetG subunit) and Glu4 (PetM subunit). Binding sites of
      quinone analogue inhibitors were sought to map the pathway of transfer of the
      lipophilic quinone across the b(6)f complex and to define the function of the
      novel heme c(n). Two sites were found for the chromone ring of the tridecyl
      stigmatellin (TDS) quinone analogue inhibitor, one near the p-side [2Fe-2S]
      cluster. A second TDS site was found on the n-side of the complex facing the
      quinone exchange cavity as an axial ligand of heme c(n). A similar binding site
      proximal to heme c(n) was found for the n-side inhibitor, NQNO. Binding of these
      inhibitors required their addition to the complex before lipid used to facilitate
      crystallization. The similar binding of NQNO and TDS as axial ligands to heme
      c(n) implies that this heme utilizes plastoquinone as a natural ligand, thus
      defining an electron transfer complex consisting of hemes b(n), c(n), and PQ, and
      the pathway of n-side reduction of the PQ pool. The NQNO binding site explains
      several effects associated with its inhibitory action: the negative shift in heme
      c(n) midpoint potential, the increased amplitude of light-induced heme b(n)
      reduction, and an altered EPR spectrum attributed to interaction between hemes
      c(n) and b(n). A decreased extent of heme c(n) reduction by reduced ferredoxin in
      the presence of NQNO allows observation of the heme c(n) Soret band in a chemical
      difference spectrum.

PMID- 17498745
TI  - Telomeric nucleosomes are intrinsically mobile.
AB  - Nucleosomes are no longer considered only static basic units that package
      eukaryotic DNA but they emerge as dynamic players in all chromosomal processes.
      Regulatory proteins can gain access to recognition sequences hidden by the
      histone octamer through the action of ATP-dependent chromatin remodeling
      complexes that cause nucleosome sliding. In addition, it is known that
      nucleosomes are able to spontaneously reposition along the DNA due to intrinsic
      dynamic properties, but it is not clear yet to what extent sequence-dependent
      dynamic properties contribute to nucleosome repositioning. Here, we study
      mobility of nucleosomes formed on telomeric sequences as a function of
      temperature and ionic strength. We find that telomeric nucleosomes are highly
      intrinsically mobile under physiological conditions, whereas nucleosomes formed
      on an average DNA sequence mostly remain in the initial position. This indicates
      that DNA sequence affects not only the thermodynamic stability and the
      positioning of nucleosomes but also their dynamic properties. Moreover, our
      findings suggest that the high mobility of telomeric nucleosomes may be relevant
      to the dynamics of telomeric chromatin.

PMID- 17498744
TI  - Adaptive evolution of a tagged chimeric gammaretrovirus: identification of novel
      cis-acting elements that modulate splicing.
AB  - Retroviruses are well known for their ability to incorporate envelope (Env)
      proteins from other retroviral strains and genera, and even from other virus
      families. This characteristic has been widely exploited for the generation of
      replication-defective retroviral vectors, including those derived from murine
      leukemia virus (MLV), bearing heterologous Env proteins. We investigated the
      possibility of "genetically pseudotyping" replication-competent MLV by replacing
      the native env gene in a full-length viral genome with that of another
      gammaretrovirus. Earlier, we developed replication-competent versions of MLV that
      stably transmit and express transgenes inserted into the 3' untranslated region
      of the viral genome. In one such tagged MLV expressing green fluorescent protein,
      we replaced the native env sequence with that of gibbon ape leukemia virus
      (GALV). Although the GALV Env protein is commonly used to make high-titer
      pseudotypes of MLV vectors, we found that the env replacement greatly attenuated
      viral replication. However, extended cultivation of cells exposed to the chimeric
      virus resulted in selection of mutants exhibiting rapid replication kinetics and
      different variants arose in different infections. Two of these variants had
      acquired mutations at or adjacent to the splice acceptor site, and three others
      had acquired dual mutations within the long terminal repeat. Analysis of the
      levels of unspliced and spliced viral RNA produced by the parental and adapted
      viruses showed that the mutations gained by each of these variants functioned to
      reverse an imbalance in splicing caused by the env gene substitution. Our results
      reveal the presence of previously unknown cis-acting sequences in MLV that
      modulate splicing of the viral transcript and demonstrate that tagging of the
      retroviral genome with an easily assayed transgene can be combined with in vitro
      evolution as an approach to efficiently generating and screening for replicating
      mutants of replication-impaired recombinant viruses.

PMID- 17498746
TI  - Optimization of the palindromic order of the TtgR operator enhances binding
      cooperativity.
AB  - TtgR is the specific transcriptional repressor of the TtgABC efflux pump. TtgR
      and the TtgB efflux pump proteins possess multidrug-binding capacity, and their
      concerted action is responsible for the multidrug resistance phenotype of
      Pseudomonas putida DOT-T1E. TtgR binds to a pseudo-palindromic site that overlaps
      the ttgR/ttgA promoters. Dimethylsulfate footprint assays reveal a close
      interaction between TtgR and the central region of this operator. The results of
      analytical ultracentrifugation demonstrate that TtgR forms stable dimers in
      solution, and that two dimers bind to the operator. Microcalorimetric analysis of
      the binding of the two TtgR dimers to the cognate operator showed biphasic
      behavior, and an interaction model was developed for the cooperative binding of
      two TtgR dimers to their target operators. The binding of the two TtgR dimers to
      the operator was characterized by a Hill coefficient of 1.63+/-0.13 (k(D)=18.2(+/
      6.3) microM, k(D)(')=0.91(+/-0.49) microM), indicating positive cooperativity.
      These data are in close agreement with the results of sedimentation equilibrium
      studies of TtgR-DNA complexes. A series of oligonucleotides were generated in
      which the imperfect palindrome of the TtgR operator was empirically optimized.
      Optimization of the palindrome did not significantly alter the binding of the
      initial TtgR dimer to the operator, but increased the cooperativity of binding
      and consequently the overall affinity. The minimal fragment for TtgR binding was
      a 30-mer DNA duplex, and analysis of its sequence revealed two partially
      overlapping inverted repeats co-existing within the large pseudo-palindrome
      operator. Based on the architecture of the operator, the thermodynamics of the
      process, and the TtgR-operator interactions we propose a model for the binding of
      TtgR to its target sequence.

PMID- 17498747
TI  - The nature and extent of organisms in vessel sea-chests: A protected mechanism
      for marine bioinvasions.
AB  - A total of 150 different organisms, including one plant species and 12 animal
      phyla were identified from sea-chests of 42 vessels visiting or operating in New
      Zealand between May 2000 and November 2004. Forty-nine percent of organisms were
      sessile, 42% mobile adults and the remaining 9% sedentary. Decapods were the most
      represented group with 19 species present among 79% of vessels. Forty percent of
      organisms were indigenous to New Zealand, 15% introduced, 10% non-indigenous, and
      35% of unknown origin. Sea-chests have the potential to (1) transfer non
      indigenous organisms between countries across oceanic boundaries; and (2)
      disperse both indigenous and introduced organisms domestically. The occurrence of
      adult mobile organisms is particularly significant and indicates that sea-chests
      may be of greater importance than ballast water or hull fouling for dispersing
      certain marine species. These findings emphasise the need to assess and manage
      biosecurity risks for entire vessels rather than different mechanisms (i.e.,
      ballast water, hull fouling, sea-chests, etc.) in isolation.

PMID- 17498748
TI  - Tumor-endothelial cell interactions: therapeutic potential.
AB  - Metastasis is the primary cause of death in cancer patients. However, the
      molecular mechanism of the metastatic process is poorly understood because it
      involves multiple steps with a high degree of complexity. A critical step for
      successful establishment of secondary colonization is the hematogenous
      dissemination of malignant cells. During this process, the attachment of cancer
      cells to the endothelial cells on microvasculature is considered to be an
      essential step and many adhesion molecules as well as chemokines have been found
      to be involved in this process. This interaction of cancer-endothelial cell is
      considered not only to determine the physical site of metastasis, but also to
      provide the necessary anchorage to facilitate tumor cell extravasation. However,
      recent evidence indicates that this interaction also serves as a host defense
      mechanism and hinders the process of metastasis. The tumor metastases suppressor
      gene, KAI1, has been known to block metastatic process without affecting the
      primary tumor growth, and this protein has been found to be able to bind to the
      chemokine receptor, Duffy antigen receptor for chemokines (DARC), which is
      expressed on endothelial cells. Importantly, this interaction markedly induces
      senescence of tumor cells. This novel finding is not only significant in the
      context of molecular dissection of metastatic process but also in the therapeutic
      implication to develop drugs inhibiting metastasis.

PMID- 17498749
TI  - Genotoxicity of non-covalent interactions: DNA intercalators.
AB  - This review provides an update on the mutagenicity of intercalating chemicals, as
      carried out over the last 17 years. The most extensively studied DNA
      intercalating agents are acridine and its derivatives, that bind reversibly but
      non-covalently to DNA. These are frameshift mutagens, especially in bacteria and
      bacteriophage, but do not otherwise show a wide range of mutagenic properties. Di
      acridines or di-quinolines may be either mono- or bis-intercalators, depending
      upon the length of the alkyl chain separating the chromophores. Those which
      monointercalate appear as either weak frameshift mutagens in bacteria, or as non
      mutagens. However, some of the bisintercalators act as "petite" mutagens in
      Saccharomyces cerevisiae, suggesting that they may be more likely to target
      mitochondrial as compared with nuclear DNA. Some of the new methodologies for
      detecting intercalation suggest this may be a property of a wider range of
      chemicals than previously recognised. For example, quite a number of flavonoids
      appear to intercalate into DNA. However, their mutagenic properties may be
      dominated by the fact that many of them are also able to inhibit topoisomerase II
      enzymes, and this property implies that they will be potent recombinogens and
      clastogens. DNA intercalation may serve to position other, chemically reactive
      molecules, in specific ways on the DNA, leading to a distinctive (and wider)
      range of mutagenic properties, and possible carcinogenic potential.

PMID- 17498750
TI  - [Intramedullary cavernomas: personal series of 24 cases].
AB  - Intramedullary cavernomas are rare, but with routinely use of MRI detection has
      improved, raising the problem of choosing the adequate management approach:
      conservative or surgical. Cavernomas are vascular malformations, but, as
      hemangioblastomas they appear as vascular tumors of the spinal cord. They can be
      durably asymptomatic. The symptoms are a progressive clinical deterioration or
      acute spinal dysfunction (tetra or paraplegia) in case of hemorrhage. Cavernomas
      have a typical aspect with MRI in contrast with intramedullary gliomas. The
      lesion is often superficial, covered by the pia-mater, visible immediately after
      opening the dura, the approach is direct; but in few cases the cavernoma is deep
      seated in the spinal cord and not visible, the approach is through the midline.
      It is recommended to perform a complete "en bloc" resection. A yearly MRI control
      is necessary to search possible "de novo" cases.

PMID- 17498751
TI  - [Introduction].

PMID- 17498752
TI  - [Familial forms of central nervous system cavernomas: from recognition to gene
      therapy].
AB  - Ten percent of all cavernomas are familial forms. 300 independent families have
      been identified in France since 1995. Clinical manifestations are more frequent
      in familial (50%) than in sporadic forms (5%). The symptoms are the same in both
      forms: epilepsy, hemorrhages, neurological focal deficits and headache, but
      hemorrhages are more frequent and the age of revelation is younger, before 30
      years. It is also frequent to observe extraneural location, cutaneous and
      retinal. On MRI, four types of lesional aspects were described and lesions are
      multiple in all cases with numerous "de novo" cavernomas. The prognostic does not
      depend on the number of lesions, but on their topography, especially in the brain
      stem. Familial forms may be considered not only as a neurological but as a
      systemic disease for which global management with a genetic counseling should be
      considered. Gene therapy is not today available, but perhaps in the future.

PMID- 17498753
TI  - [Surgical anatomy of the brain stem].
AB  - We reviewed the literature on brain stem anatomy, to identify possible and non
      hazardous entry zones with a minimum of functional risks. Using the reticular
      formation defined as a median structure in a coronal plane, we determined six
      anatomic zones, 3 ventral, 3 dorsal (mesencephalic, pontic, medulla-oblongata).
      Considering the functional structures surrounding each zone, the possible
      penetration points are described. There are ventral, one for the mesencephale,
      one for the pons, one for the medulla oblongata; and dorsal, one for the
      mesencephale, two for the floor of the 4th ventricle, one for the medulla
      oblongata.

PMID- 17498754
TI  - [Role of radiosurgery in the management of intracranial cavernomas. Review of the
      literature].
AB  - From a review of the literature dealing with radiosurgery of cavernous
      malformations, we have analyzed its impact on hemorrhagic risk, epilepsy,
      histological modifications, morbidity and potential indications of treatment.
      Radiosurgery could significantly reduce the hemorrhagic risk, in a selected
      population with a high risk of hemorrhage, after an interval of about 2 years,
      but cannot provide protection against rebleeding. As for epilepsy related to the
      lesion, a significant reduction of seizures has been observed in certain cases,
      with better control in case of recent evolution and simple seizures linked to the
      site of the vascular malformation. Histologic lesions are vascular fibrosis,
      fibrinoid necrosis and ferrugination, without good correlation with results of CT
      scan or MRI. Morbidity of radiosurgery seems higher compared to other diseases
      with similar doses and target volumes. The rate of transient complications was
      about 25%, with permanent sequelae in 5 to 10% of patients. This would be due to
      a radiosensitizing effect of the hemosiderin halo around the lesion. Radiosurgery
      can be proposed for non-surgical lesions with a high risk of hemorrhage,
      nevertheless the superiority of the technique over conservative treatment has to
      be proven. Without long-term prospective studies, the efficiency of RS for
      cavernomas remains questionable and subject to debate. New imaging methods
      proving the obstruction of the cavernous malformation are needed.

PMID- 17498755
TI  - [Therapeutic indications for central nervous system cavernomas].
AB  - We describe the therapeutic indications for central nervous system cavernomas
      based on three criteria: 1) Single and multiple lesions: indications are the
      same, considering that in multiple lesions, one location can be symptomatic; 2)
      locations: indications are easy to define for exophytic cavernomas close to the
      hemisphere, brain stem or cerebellum pial surface, or to the ventricular
      ependyma; 3) symptomatic and non symptomatic presentations: usually, symptomatic
      forms require surgery except deep lesions located in functional zones distant
      from the ependyma or the pia matter, unless life prognosis is compromised.
      Treatment of a symptomatic forms remains debatable, opinion being divided between
      therapeutic abstention and surgery (in case of cavernomas close to the pia matter
      or the ependyma). Scientific data strongly support surgical indication for
      lesions presenting with epilepsy specially when drug-resistant; 4) natural
      history: prevention against hemorrhage is an argument in favor of surgery for the
      lesions located in non functional zones or where the risk of bleeding is higher,
      especially in the brain stem. Discrepancy in the risk of bleeding reported in the
      literature tends to temper this attitude. Radiosurgery is exceptionally reserved
      for technically inoperable cavernomas. Partial protection for two years can be
      expected. Epileptic seizures decrease but few prospective randomised studies are
      available. The rate of complication appears to be higher than in other
      affections.

PMID- 17498756
TI  - [Histopathology of central nervous system cavernomas].
AB  - Central nervous system cavernomas are vascular malformations, which occur in two
      circumstances: sporadic forms and familial autosomal dominant forms. The lesion
      consists of enlarged, closely packed vessels without interposition of brain
      parenchyma, surrounded by hemosiderin and gliosis, calcified in few cases. In 80%
      of sporadic forms the lesion is unique, multiple lesions are rare (median: 4). In
      familial forms the lesions are always multiple. Cavernomas are often associated
      with other vascular malformations, especially with venous developmental
      anomalies. The size of cavernomas is variable from 1 mm to several centimeters.
      About 70% of cases are supratentorial and 30% in the posterior fossa,
      particularly in the brain stem. Macroscopic and histopathological findings are
      typical and the diagnostic is generally easy.

PMID- 17498757
TI  - Body composition and endocrine status of long-term stress-induced binge-eating
      rats.
AB  - Clinical binge eating runs a protracted course. The etiology of binge eating
      remains perplexing in part because, in humans, it is difficult to isolate and
      assess the independent and aggregate impact of various contributing variables.
      Using rats, we found that footshock stress and a history of caloric restriction
      (S+R), combine synergistically to induce binge eating. Stress and dieting are
      also strong antecedents and relapse factors in human eating disorders. Here we
      report further behavioral and physiological parallels to human binge eating. Like
      the protracted course of human binge eating, young female Sprague-Dawley rats
      continued to binge eat after 23 restriction/stress cycles (7 months) and this
      despite experiencing no significant weight loss during the restriction phases.
      Stress alone reduced adiposity by 35% (p<0.001) but S+R rats had no significant
      fat loss. An endocrine profile of normal plasma leptin and insulin levels but
      marked elevation of plasma corticosterone levels was found only in the binge
      eating (S+R) rats (p<0.01), also paralleling endocrine profiles reported in
      clinical binge-eating studies. These behavioral and physiological similarities
      between this animal model and clinical binge eating increase its utility in
      understanding binge eating. Importantly, our findings also highlight the stubborn
      nature of binge eating: once a critical experience with dieting and stress is
      experienced, little if any further weight loss or food restriction is necessary
      to sustain it.

PMID- 17498758
TI  - Control of food consumption by learned cues: a forebrain-hypothalamic network.
AB  - Motivation plays an important role in the control of food intake. This review
      will focus on recent findings using a neural systems analysis of a behavioral
      model for learned motivational control of eating. In this model, environmental
      cues that acquire motivational properties through Pavlovian conditioning can
      subsequently override satiety and promote eating in sated rats. Evidence will be
      presented that a brain network formed by the amygdala, lateral hypothalamus, and
      medial prefrontal cortex mediates this phenomenon of conditioned potentiation of
      feeding. The animal model may be informative for understanding control of eating
      in humans including maladaptive influences that contribute to overeating.

PMID- 17498759
TI  - Prolactin and the hyperphagia of lactation.
AB  - The nutritional needs of developing young place a large energetic demand on
      lactating females. In this paper some of the mechanisms through which lactating
      rats meet these demands are described. Emphasis is placed on the mechanisms that
      drive increased food intake in suckled rats that are independent of milk delivery
      and negative energy balance. Evidence is presented to suggest that prolactin
      (PRL), released from the pituitary in response to suckling stimulation, acts
      centrally to stimulate food intake during lactation. Brain areas in which PRL may
      act to stimulate food intake as well as its interactions with other hormones and
      neuropeptides involved in energy balance are discussed.

PMID- 17498761
TI  - Phenolic glycosides from Foeniculum vulgare fruit and evaluation of antioxidative
      activity.
AB  - Two diglucoside stilbene trimers and a benzoisofuranone derivative were isolated
      from Foeniculum vulgare fruit together with nine known compounds. Their
      structures were elucidated by spectral methods including 1D, 2D NMR and MS and
      chemical methods. Antioxidant activity was tested using three methods: DPPH(),
      total antioxidant capacity and assay of lipid peroxidation.

PMID- 17498760
TI  - Effects of polychlorinated biphenyls on maternal odor conditioning in rat pups.
AB  - Polychlorinated biphenyls (PCBs) are pervasive environmental contaminants that
      can have damaging effects on physiologic, motoric and cognitive function. Results
      from studies on PCBs and behavior have shown that exposure can alter learning and
      memory processes and that these shifts in cognitive abilities can be related to
      changes in hormonal and neural function. Little experimentation has been done on
      the impact of exposure to PCBs on social and emotional development. Previous work
      has shown that exposure to PCBs in children can alter play behavior. Importantly,
      exposure to PCBs has been found to change aspects of maternal-offspring
      interactions in rodents. The present study examined the impact of PCBs on
      maternal odor conditioning in rat pups 12-14 days of age. A modified version of
      the conditioned place preference paradigm was used that incorporated a maternal
      associated odor cue (lemon scent) as the conditioned stimulus. PCBs significantly
      depressed the preference for the maternal-associated cue but did not impair
      discrimination for a novel odor. These effects could arise due to changes in the
      social dynamics between the dam and offspring after co-exposure to PCBs. For
      example, dams exposed to PCBs during gestation have been found to show elevated
      grooming directed towards pups exposed to PCBs. This change in maternal care can
      have dramatic effects on behavioral and hormonal systems in the developing rat
      pup. In conclusion, perinatal PCBs alter important social behaviors of both the
      mother and pup, and these alterations could have long-lasting effects on
      behavioral, cognitive and emotional development.

PMID- 17498762
TI  - AIDS prevention in late adolescent college students from Spain and Portugal.
AB  - OBJECTIVES: The aim of this study was to determine the factors related to the
      adoption of effective methods for preventing AIDS, particularly condom use, in
      university students from Spain and Portugal. STUDY DESIGN: A cross-sectional and
      cross-cultural study. Data were obtained by questionnaire. METHOD: The variables
      analysed in the sample of Spanish and Portuguese students were: the perceptions
      of benefits and barriers to condom use; perceived self-efficacy in the
      negotiation of condom use; and in using a condom in difficult situations; and the
      perceptions of vulnerability, severity and risk. RESULTS: The data showed
      similarities between the Spanish and Portuguese students in the high frequency of
      condom use and the weight of self-efficacy for negotiating and ensuring condom
      use. However, data also reflected differences between the countries especially
      with regard to the weight of benefits and costs in the adoption of prevention
      methods. CONCLUSIONS: These findings suggest that the different realities for
      each country or context must be considered in the design of AIDS prevention
      programmes aimed at late adolescents. Whereas in both countries prevention
      programmes should encourage the ability to negotiate condom use, Portuguese
      programmes must underline the benefits of condom use, and Spanish programmes
      should aim to analyse the importance of barriers to condom use for the students
      to reduce these and to replace costs with benefits.

PMID- 17498763
TI  - Nicotine promotes cell proliferation via alpha7-nicotinic acetylcholine receptor
      and catecholamine-synthesizing enzymes-mediated pathway in human colon
      adenocarcinoma HT-29 cells.
AB  - Cigarette smoking has been implicated in colon cancer. Nicotine is a major
      alkaloid in cigarette smoke. In the present study, we showed that nicotine
      stimulated HT-29 cell proliferation and adrenaline production in a dose-dependent
      manner. The stimulatory action of nicotine was reversed by atenolol and ICI
      118,551, a beta(1)- and beta(2)-selective antagonist, respectively, suggesting
      the role of beta-adrenoceptors in mediating the action. Nicotine also
      significantly upregulated the expression of the catecholamine-synthesizing
      enzymes [tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DbetaH) and
      phenylethanolamine N-methyltransferase]. Inhibitor of TH, a rate-limiting enzyme
      in the catecholamine-biosynthesis pathway, reduced the actions of nicotine on
      cell proliferation and adrenaline production. Expression of alpha7-nicotinic
      acetylcholine receptor (alpha7-nAChR) was demonstrated in HT-29 cells.
      Methyllycaconitine, an alpha7-nAChR antagonist, reversed the stimulatory actions
      of nicotine on cell proliferation, TH and DbetaH expression as well as adrenaline
      production. Taken together, through the action on alpha7-nAChR nicotine
      stimulates HT-29 cell proliferation via the upregulation of the catecholamine
      synthesis pathway and ultimately adrenaline production and beta-adrenergic
      activation. These data reveal the contributory role alpha7-nAChR and beta
      adrenoceptors in the tumorigenesis of colon cancer cells and partly elucidate the
      carcinogenic action of cigarette smoke on colon cancer.

PMID- 17498764
TI  - Bacterial degradation of microcystin toxins in drinking water eliminates their
      toxicity.
AB  - Microcystin-LR and -LA were readily biodegraded by a bacterium, Sphingpoyxis sp.
      LH21, in a treated reservoir water. Detection of the microcystins was conducted
      using high-performance liquid chromatography (HPLC), protein phosphatase 2A
      (PP2A) inhibition assay and a cell-based cytotoxicity assay. The HPLC results
      correlated well with the two assays. The decrease in cytotoxicity, coupled with
      the associated decrease in microcystin concentrations, indicated that no
      cytotoxic by-products were being generated, highlighting the applicability of
      biodegradation as a feasible treatment option for effective microcystin removal.

PMID- 17498765
TI  - Natural genetic variations in bovine leukemia virus envelope gene: possible
      effects of selection and escape.
AB  - Bovine leukemia virus (BLV) is an oncogenic virus widespread in cattle. It
      belongs to the genus Deltaretrovirus of the family Retroviridae along with human
      and simian T-lymphotropic viruses. Here we report the addition of 28 new
      sequences to the current literature of 16 full-length BLV envelope gene
      sequences. The phylogenetic clustering, genotyping, and geographic distribution
      of BLV env variations corresponded in most cases. Most natural variations are
      mapped to the surface of the proposed conformational models of BLV gp51 N
      terminus and gp30 external domain, overlapping with or adjacent to immunogenic
      epitopes. Analyses for evidence of possible selection pressures suggest the BLV
      env is under stringent negative selection overall, while strong positive
      selection is indicated for immunogenic epitope G. Natural env deletions bounded
      by similar flanking sequences were observed in multiple isolates and would result
      in truncated signal peptides, missing gp51, and aberrant coding frames for other
      proteins.

PMID- 17498766
TI  - Influences on hepatitis B virus replication by a naturally occurring mutation in
      the core gene.
AB  - Little is known about specific naturally occurring mutations of hepatitis B virus
      (HBV) and underlying mechanisms of their association with fulminant hepatitis. A
      HBV clone isolated from a patient with fulminant hepatitis was analyzed, and the
      features of the particular mutations observed around furin cleavage site in core
      region (A2339G/G2345A) were assessed using an in vitro replication model. The
      clone belonged to genotype B with precore stop codon mutation (G1896A).
      Replication efficiency of 1.24-fold HBV genome in Huh-7 cells was increased in
      the presence of A2339G. Further in vitro studies using furin inhibitor indicated
      that the effect of the mutation was probably associated with accumulation of the
      full-length core protein without cleavage by furin-like protease, suggesting that
      a processing of the core protein might play an important role in regulation of
      viral replication. In conclusion, the A2339G mutation was considered as one of
      the viral factors involved in high replication efficiency.

PMID- 17498767
TI  - Entry of hepatitis C virus and human immunodeficiency virus is selectively
      inhibited by carbohydrate-binding agents but not by polyanions.
AB  - We studied the antiviral activity of carbohydrate-binding agents (CBAs),
      including several plant lectins and the non-peptidic small-molecular-weight
      antibiotic pradimicin A (PRM-A). These agents efficiently prevented hepatitis C
      virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infection of target
      cells by inhibiting the viral entry. CBAs were also shown to prevent HIV and HCV
      capture by DC-SIGN-expressing cells. Surprisingly, infection by other enveloped
      viruses such as herpes simplex viruses, respiratory syncytial virus and
      parainfluenza-3 virus was not inhibited by these agents pointing to a high degree
      of specificity. Mannan reversed the antiviral activity of CBAs, confirming their
      association with viral envelope-associated glycans. In contrast, polyanions such
      as dextran sulfate-5000 and sulfated polyvinylalcohol inhibited HIV entry but
      were devoid of any activity against HCV infection, indicating that they act
      through a different mechanism. CBAs could be considered as prime drug leads for
      the treatment of chronic viral infections such as HCV by preventing viral entry
      into target cells. They may represent an attractive new option for therapy of
      HCV/HIV coinfections. CBAs may also have the potential to prevent HCV/HIV
      transmission.

PMID- 17498768
TI  - Extensions to modeling aerobic carbon degradation using combined respirometric
      titrimetric measurements in view of activated sludge model calibration.
AB  - Recently a model was introduced to interpret the respirometric (OUR) -titrimetric
      (Hp) data obtained from aerobic oxidation of different carbon sources in view of
      calibration of Activated Sludge Model No.1 (ASM1). The model requires, among
      others, the carbon dioxide transfer rate (CTR) to be relatively constant during
      aerobic experiments. As CTR is an inherently nonlinear process, this assumption
      may not hold for certain experimental conditions. Hence, we extended the model to
      describe the nonlinear CTR behavior. A simple calibration procedure of the CO2
      model was developed only using titrimetric data. The identifiable parameter
      subset of this model when using titrimetric data only contained the first
      equilibrium constant of the CO2 dissociation, pK1, the initial aqueous CO2
      concentration, C(Tinit) and the nitrogen content of biomass, i(NBM). The extended
      model was then successfully applied to interpret typical data obtained from
      respirometric-titrimetric measurements with a nonlinear CO2 stripping process.
      The parameter estimation results using titrimetric data were consistent with the
      results estimated using respirometric data (OUR) alone or combined OUR and Hp
      data, thereby supporting the validity of the dynamic CO2 model and its
      calibration approach. The increased range of applicability and accurate
      utilization of the titrimetric data are expected to contribute particularly to
      the improvement of calibration of ASM models using batch experiments.

PMID- 17498769
TI  - Chlorine photolysis and subsequent OH radical production during UV treatment of
      chlorinated water.
AB  - The photodegradation of chlorine-based disinfectants NH(2)Cl, HOCl, and OCl(-)
      under UV irradiation from low- (LP) and medium-pressure (MP) Hg lamps was
      studied. The quantum yields of aqueous chlorine and chloramine under 254 nm (LP
      UV) irradiation were greater than 1.2 mol Es(-1) for free chlorine in the pH
      range of 4-10 and 0.4 mol Es(-1) for monochloramine at pH 9. Quantum yields for
      MP (200-350 nm) ranged from 1.2 to 1.7 mol Es(-1) at neutral and basic pH to 3.7
      mol Es(-1) at pH 4 for free chlorine, and 0.8 mol Es(-1) for monochloramine.
      Degradation of free chlorine was enhanced under acidic water conditions, but
      water quality negatively impacted the MP Hg lamp degradation of free chlorine,
      compared to the LP UV source. The production of hydroxyl radical via chlorine
      photolysis was assessed along with the rate of reaction between (*)OH and HOCl
      using radical scavengers (parachlorobenzoic acid and nitrobenzene) in chlorinated
      solutions at pH 4. The quantum yield of OH radical production from HOCl at 254 nm
      was found to be 1.4 mol Es(-1), while the reaction of HOCl with OH radical was
      measured as 8.5 x 10(4)M(-1)s(-1). NH(2)Cl was relatively stable in all
      irradiated solutions, with <0.3 mg L(-1) increase in nitrate following a UV dose
      of 1000 mJ cm(-2). For water treatment plants, no significant changes in chlorine
      concentration would be expected under typical pH levels and UV doses; however,
      the formation of (*)OH could have implications for chlorinated byproducts or
      decay of unwanted chemical contaminants.

PMID- 17498770
TI  - High concern chemicals in top layer sediments of the northern Adriatic seabed as
      markers of old waste dumpings.
AB  - The results are presented of a survey planned to assess the presence of high
      concern chemicals in sediments collected in a northern sector of the Adriatic sea
      neighboring the Venice lagoon. For the assessment, persistent marker chemicals
      were selected from the families of polycyclic aromatic hydrocarbons,
      polychlorobiphenyls, polychlorodibenzo-p-dioxins (PCDDs), polychlorodibenzofurans
      (PCDFs), and chlorinated pesticides. Based on the chemical-specific
      concentrations and PCDD+PCDF profiles determined in the sediments analyzed,
      dumping zones appear to have existed approximately 5-6km away from lagoon
      shoreline. Contamination levels exceed the quality criteria established by the
      pertinent Italian national regulation at many sampling sites, eventually
      reflecting ("fingerprinting") industrial activities once performed in the
      industrial settlement of Porto Marghera within the Venice lagoon. In coastal
      samples, concentration levels appear to be lower than those determined at
      offshore sampling sites.

PMID- 17498771
TI  - Environmental fate of chlorothalonil in a Costa Rican banana plantation.
AB  - The environmental fate of chlorothalonil (CHT) and its metabolites were studied
      under field-variable conditions in a commercial banana plantation in Costa Rica.
      Weather conditions were representative of a tropical environment and the
      fungicide applications were typical of those in banana production. The test plots
      were treated with Bravo 720 at 1.2 l ha(-1) of formulated product. Field
      persistence of CHT in soil and on banana leaves was measured during five
      consecutive months and after three aerial applications of the fungicide. Residues
      were analyzed in soil, sediment, water, banana leaves and drift cards by gas and
      liquid chromatography coupled to mass spectrometry. In soil and on the surface of
      banana leaves, CHT dissipated rapidly with half-lives of 2.2 and 3.9 d,
      respectively. Soil residues persisted and were detected 85 d after application.
      The main metabolite found in soil, 4-hydroxy-chlorothalonil, accounted for
      approximately 65% of residues detected and was measured up to 6d after
      application.

PMID- 17498772
TI  - Oxidation of natural and synthetic hormones by the horseradish peroxidase enzyme
      in wastewater.
AB  - Steroid estrogens, including both natural estrogens (e.g., estrone - E1; 17beta
      estradiol - E2; and estriol - E3) and synthetic estrogens (e.g., 17alpha
      ethinylestradiol - EE2), are known as endocrine-disrupting compounds. The
      objective of this research was to evaluate the feasibility of the enzymatic
      oxidation of estrogens and to optimize this process in municipal wastewater
      contaminated with steroid estrogens using horseradish peroxidase (HRP) and
      hydrogen peroxide. An initial HRP activity of 0.02 U ml(-1) was sufficient to
      completely remove EE2 from the synthetic solution, although greater HRP doses (up
      to 0.06 U ml(-1)) were required to remove E1, E2 and E3. The optimal molar
      peroxide-to-substrate ratio was determined to be approximately 0.45. Based on the
      Michaelis-Menten kinetics, the HRP had an increasing reactivity with E1, E3, E2,
      and EE2, in increasing order. In real activated sludge process effluent, an HRP
      dose of 8-10 U ml(-1) was required to completely remove all of the studied
      estrogens, while only 0.032 U ml(-1) of HRP was necessary to treat synthetic
      water containing the same estrogen concentrations.

PMID- 17498773
TI  - Desorption of PCDD/PCDF from municipal solid waste incinerator flyash under post
      combustion plant conditions.
AB  - The influence of temperature on the levels of PCDD and PCDF remaining in, and
      desorbed from, a municipal solid waste incinerator flyash was investigated by
      heating the ash to between 200 and 400 degrees C under a simulated flue gas for
      four days reaction time. Considerable desorption of PCDD/PCDF from the flyash was
      seen at 275 degrees C and above. Maximum desorption occurred at 350 degrees C,
      with the equivalent of nearly eight times the total PCDD/PCDF concentration of
      the original flyash being lost to the vapour phase per unit mass of initial
      flyash. The I-TEQ value of the desorbed PCDD/PCDF was considerable, being over
      fourteen times that of the original flyash at 325 degrees C. The results indicate
      that formation of PCDD/PCDF on flyash deposits in the post-combustion plant of
      incinerators can result in the release of significant amounts of PCDD/PCDF to the
      flue gas stream.

PMID- 17498774
TI  - Evaluation of the thermal/optical reflectance method for quantification of
      elemental carbon in sediments.
AB  - The IMPROVE thermal/optical reflectance (TOR) method, commonly used for EC
      quantification in atmospheric aerosols, is applied to soils and sediments and
      compared with a thermochemical method commonly applied to these non-atmospheric
      samples. TOR determines elemental carbon (EC) by an optical method, but it also
      yields thermally defined EC fractions in a 2% O2/98% He oxidizing atmosphere at
      550 degrees C (EC1), 700 degrees C (EC2), and 800 degrees C (EC3). Replicate TOR
      TC, OC, and EC values exhibited precisions of approximately +/-10% as determined
      from multiple analyses of the same samples. EC abundances relative to total mass
      concentrations were within the ranges reported by other methods for diesel
      exhaust soot, n-hexane soot, wood and rice chars, and coals, as well as for
      environmental matrices. A direct comparison with the chemothermal (CTO) method of
      Gustafson et al. for ten soil and sediment samples demonstrated that almost all
      of the OC and EC1 are eliminated, as is part of the EC2. The CTO soot carbon is
      bounded by the EC3 and EC2+EC3 fractions of the IMPROVE TOR analysis. It might be
      possible to adjust these fractions to obtain better agreement between atmospheric
      aerosol and soil/sediment analysis methods. Given its linking the EC measurement
      in the atmosphere to sediments, the TOR method will not only provide useful
      information on the explanation and comparison between different environmental
      matrices, but also can be used to derive information on global cycling of EC.

PMID- 17498775
TI  - Carnitine, acylcarnitine and amino acid profiles analyzed by tandem mass
      spectrometry in a surfactant/virus mouse model of acute hepatic encephalopathy.
AB  - Tandem mass spectrometry (MS/MS) was used to analyze multiple serum metabolites
      for the first time in a surfactant/virus mouse model of acute hepatic
      encephalopathy (AHE). AHE is characterized by acute liver failure that can lead
      to potentially lethal increases in intracranial pressure. We have reproduced AHE
      in young CD-1 mice exposed from postnatal day (P) 2-13 to the industrial
      surfactant, Toximul 3409F (Tox), and then infected intranasally on P14 with
      sublethal doses (LD(10-30)) of mouse-adapted human influenza B (Lee) virus
      (FluB). The sera analyzed by MS/MS were from mice exhibiting typical markers of
      Tox-mediated potentiation of viral illness, including reduced weights and blood
      glucose levels. Most metabolite abnormalities were not evident until five days
      after viral infection (P19), the time corresponding to the onset of weight loss
      and mortality. Values for fatty acylcarnitines and amino acids in the Tox+FluB
      treated mice were either additive or supra-additive relative to the effects of
      either treatment alone. Amino acid profiles were consistent with those reported
      for human AHE. None of the treated mice exhibited signs of carnitine deficiency,
      and propionylcarnitine levels were normal. On P19, mice given combined Tox+FluB
      treatment had significant increases in levels of both medium- and long-chain
      acylcarnitines (C6:0-C12:0 and C14:0-C20:0, respectively), including their
      monounsaturated metabolites. Levels of medium-chain dicarboxylic and long-chain
      hydroxy-acylcarnitines were also elevated in the combined treatment group. The
      results of this study indicate a diffuse mitochondrial dysfunction in Tox+FluB
      treated mice that results in a serum metabolite profile unique from those
      observed in classic inherited metabolic disorders.

PMID- 17498776
TI  - Ecological risk assessment using RAPD and distribution pattern of a rare and
      endangered species.
AB  - Environmental and ecological risk assessment always provide useful evidence for
      characterisation and conservation of the rare and endangered species, e.g. seven
      son flower (Heptacodium miconioides Rehd.). Seven-son flower is a deciduous arbor
      species, but endangered, with a restricted distribution in the subtropical
      forests of China. Genetic risk assessment of 56 samples of the flower from nine
      main populations in Zhejiang (China) was carried out by using the RAPD analysis.
      This was to study the ecological characteristics, spatial distribution and
      genetic features of the seven-son flower communities and establish a feasible
      conservation plan. Twenty-one primers screened from 50 yielded 119 RAPD bands
      with 72 polymorphic products and 60.50% of total bands. The genetic variation was
      found to be partitioned mainly among rather than within populations. Percentages
      of genetic diversity among populations were quantified by Shannon index and the
      Nei's gene diversity coefficient. AMOVA also demonstrated that these relict
      populations were highly differentiated. The high level of population variation
      observed is in contrast to that expected for a primarily outcrossed woody
      perennial plant, and suggests that there may be a degree of inbreeding. The
      dendrogram constructed from genetic distances through UPGMA method based on Nei's
      coefficients shows two groups among nine population clusters, which is further
      supported by a principle components analysis (PCA) of RAPD phenotypic data. The
      analysis showed that the biologic characteristics and habitat fragmentation were
      the reasons of the great genetic variation among populations. Some strategies of
      its genetic diversity conservation were proposed in the fragmented habitats based
      on its genetic structure and its biological characteristics in this study.

PMID- 17498777
TI  - Fluorescence fingerprints and Cu2+-complexing ability of individual molecular
      size fractions in soil- and waste-borne DOM.
AB  - Land spreading of organic materials introduces large amounts of dissolved organic
      matter (DOM) into the soil. DOM has the ability to form stable complexes with
      heavy metals and can facilitate their transport towards the groundwater. The
      effects on soil processes are difficult to assess, because different DOM
      components might react differently towards metal ions. The objective of this
      study was to investigate the fluorescence signature and the Cu2+-binding capacity
      of individual molecular size fractions of DOM from various sources. DOM extracted
      from leaf compost, chicken manure, sugar cane vinasse and a fulvic hypercalcaric
      cambisol was fractionated by the means of dialysis into four molecular size
      classes: MW<500, 500<MW<3500, 3500<MW<12000-14000, and MW>12000-14000 Da. Vinasse
      and leaf compost contained around 80% and 70%, respectively, of the total organic
      carbon in the fractions with low molecular weight (MW<3500 Da); in chicken manure
      and soil these fractions accounted for 40% and 50% only. Fluorescence was highest
      in the fraction MW>12000 Da for leaf compost, chicken manure and soil. The
      opposite result was obtained for vinasse, where the fractions with low molecular
      weight showed highest fluorescence intensities, distinguishing it from all other
      samples. Vinasse showed the greatest ability to bind Cu2+ with a resulting
      complex concentration of 6.31mgl(-1) while in contact with an excess of Cu2+.
      Leaf compost, soil and chicken manure followed with 2.69, 1.12, and 0.85mgl(-1),
      respectively. Within vinasse, the fraction MW<500 Da was able to form the most
      DOM-Cu complexes, indicating the importance of low molecular weight fractions in
      metal binding.

PMID- 17498778
TI  - Historical trends of PCDD/Fs and dioxin-like PCBs in sediments buried in a
      reservoir in Northern Taiwan.
AB  - Polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofuran (PCDF) and
      polychlorinated biphenyl (PCB) concentrations were analyzed at 1-2cm intervals in
      a sediment core collected from a reservoir in Northern Taiwan to evaluate the
      organic pollution history. The highest PCDD/F (14.4ng TEQ/kg d.w.) and PCB
      (0.261ng TEQ(WHO)/kg d.w.) concentrations were determined at 13-15cm (estimated
      year: 1992). The ages of the levels of sediment core were estimated from the
      sedimentation rate. Analysis results demonstrate that the PCDD/F concentration of
      the sediment core measured in the reservoir reached their peak when the municipal
      waste incinerators (MWIs) in the area started to operate. Furthermore, the
      decrease in sediment core PCDD/F concentration is related to the time of
      enforcement of the PCDD/F emission limit set by the Environmental Protection
      Administration (EPA) in Taiwan. Significant distribution of OCDD in homologue
      profiles was noted in archived soil samples in Taiwan in which the major input of
      PCDD/Fs was thought to be atmospheric. Major PCB congeners found in the sediment
      core were the major components of the commercial PCB products. Input fluxes of
      PCDD/Fs (5.75-158ng-I-TEQ/m(2)-yr) and PCBs (0.248-3.71ng TEQ(WHO)/m(2)yr) into
      the reservoir of interest are also calculated from the concentration and
      sedimentation rate of the sediment. The results reveal that considerable amounts
      of PCDD/Fs and PCBs were carried into the reservoir of interest in the flood
      stage but not during normal stage.

PMID- 17498779
TI  - Emission factors and characteristics of criteria pollutants and volatile organic
      compounds (VOCs) in a freeway tunnel study.
AB  - Carbon monoxide (CO), nitrogen oxide (NO(x)), hydrocarbon (HC), sulfur oxide
      (SO(2)), particulate matter <10 microm (PM(10)), and 57 VOC species of emissions
      were confirmed in a freeway tunnel in southern Taiwan. Emission factors were 1.89
      (CO), 0.73 (NO(x)), 0.46 (HC), 0.02 (SO2) and 0.06 (PM(10)) g/km-vehicle for all
      vehicle fleets. Heavy-duty truck and trailer vehicles contributed 20% of the
      emissions on workdays and 9.5% on weekends in this study. Paraffins and aromatics
      were the main VOC groups in the tunnel. Isopentane, toluene, n-pentane, isoprene,
      2,3-dimethylbutane, acetone, 2-methylpentane, 1-hexene, 1,2,4-trimethybenzene, 1
      butene and propene emissions were the major VOC species. Their emission factors
      were over 10 mg/km-vehicle. Rainfall and high humidity in the tunnel could have
      reduced the VOC concentrations and increased the portion of aromatics. In
      addition to paraffins, olefins, and aromatic compounds, oxygenated compounds
      (i.e., acetone) were found. The pollutant ratios between the inside center and
      the outside of the tunnel were about 2-3 for CO, SO2, and PM(10) and 42 for
      NO(x). In addition, the emission factors of the vehicles could reflect real-world
      vehicle emissions on the highway and be used as baseline information for
      development of a vehicle control strategy.

PMID- 17498780
TI  - The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene
      concentrations in Chinese coke oven workers.
AB  - Urinary 1-hydroxypyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbons
      (PAHs) exposure, may be influenced by metabolic gene polymorphisms. Such
      knowledge could benefit us in understanding the inter-individual difference in
      the mechanism of PAHs-induced carcinogenesis. We investigated the influence of
      gene polymorphisms on urinary 1-OHP concentrations in 447 coke oven workers from
      two coking plants in south China. After adjustment for age, plant, level of
      occupational exposure, body mass index, level of education, alcohol consumption,
      cigarette smoking and respirator usage, AhR R554K (rs2066853), UGT1A1 -3263T>G
      (rs4124874) and GSTP1 I105V (rs1695) were associated with urinary 1-OHP excretion
      with the p-value of 0.053, 0.006 and 0.021, respectively. The concentrations of
      urinary 1-OHP (Geometric mean, micromol/mol creatinine) in the homozygous major
      variant carriers and homozygous minor variant carriers for AhR R554K, UGT1A1 
      3263T>G and GSTP1 I105V were listed as follows: 4.20 and 5.12, 5.11 and 3.92,
      4.93 and 2.91, respectively. GSTT1 present carriers had a significantly higher
      urinary 1-OHP level than that in null carriers in the case with AhR R554K GA/AA
      carriers (5.17 vs. 3.64 micromol/mol creatinine, p=0.038), as well as in the case
      with UGT1A1 -3263T>G TG/GG carriers (5.67 vs. 3.38 micromol/mol creatinine,
      p=0.001). These results showed that AhR, UGT1A1, GSTP1 and GSTT1 polymorphisms
      were associated with urinary 1-OHP concentrations in Chinese coke oven workers.
      No influence was found in the association between urinary 1-OHP and other genetic
      polymorphisms such as CYP1A1, CYP1A2, CYP1B1, CYP2E1, EPHX1, EPHX2 in this
      population.

PMID- 17498781
TI  - Use of systemic therapy in women with recurrent ovarian cancer--development of a
      national clinical practice guideline.
AB  - OBJECTIVE: To develop a guidance document concerning the use of systemic therapy
      for women with recurrent ovarian cancer that would be applicable for the Canadian
      health care system. This will be done using a standardized systematic review
      process, guideline evaluation instruments, multi-disciplinary expert consensus
      opinion and evidence-rating systems. DATA SELECTION: The primary data sources
      were MEDLINE, National Guideline Clearinghouse and Cochrane Library. METHODS:
      Clinical practice guidelines, technology assessments, systematic reviews and
      randomized controlled trials addressing systemic therapy for women with recurrent
      ovarian cancer were eligible. DATA EXTRACTION: Data was identified and extracted
      by the methodology team and reviewed by the authors. Results were reviewed and
      discussed by members of an expert working group comprised of a multidisciplinary
      and geographic divergent group of practitioners. DATA SYNTHESIS: The existing 7
      practice guidelines underwent formal evaluation for quality, currency and content
      using the AGREE tool. Recommendations with evidence-ratings were developed. This
      data was used by a pan-Canadian panel in an informal consensus process, which
      resulted in the initial draft of a guideline. The guideline team reviewed the
      draft and made further edits to ensure the guideline's appropriateness for a
      national context. Practitioner feedback was requested from 165 health care
      providers who treat ovarian cancer from across Canada. Overall response rate was
      37% and was very positive. Comments were reviewed and the guideline was edited
      appropriately. CONCLUSION: The development of a national practice guideline on
      the use of systemic therapy for recurrent ovarian cancer was feasible using
      systematic literature review, expert consensus, guideline evaluation instruments,
      evidence-rating systems, independent internal and external review measures and
      final approval by a national discipline specific society (GOC). Recommendations
      for practice are offered.

PMID- 17498782
TI  - Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis
      in ovarian carcinoma.
AB  - OBJECTIVE: Cyclic platinum-based intraperitoneal chemotherapy has proven to be
      effective after optimal surgical cytoreduction in ovarian carcinoma. Hyperthermia
      is directly cytotoxic and enhances chemotherapy tumoricidal effects. This study
      was designed to determine the maximum tolerated dose (MTD) of carboplatin used
      intraoperatively as intraperitoneal hyperthermic chemotherapy (IPHC), the effect
      on postoperative systemic chemotherapy administration, and the potential for
      repeat IPHC at second look surgery. METHODS: Using the ThermoChem HT System,
      escalating doses of carboplatin (400, 600, 800, 1000, and 1200 mg/m(2)) were
      administered intraoperatively as IPHC with a perfusion time of 90 min. A subgroup
      of eight patients that received initial IPHC and subsequent systemic chemotherapy
      underwent second look reassessment surgery with IPHC. RESULTS: The first 4 dose
      levels were well tolerated without dose-defining toxicity. The initial two
      patients treated at 1200 mg/m(2) developed grade 4 myelosuppression thus defining
      the MTD at 1000 mg/m(2). Newly diagnosed ovarian cancer patients receiving the
      initial IPHC at the MTD defined above completed standard systemic chemotherapy
      with six courses of systemic chemotherapy. Eight patients having initial IPHC and
      systemic chemotherapy subsequently had repeat IPHC performed at second look
      laparotomy without grade 3 or 4 toxicities. Four patients were found to have
      extensive adhesions at the time of second look reassessment surgery yet completed
      IPHC. CONCLUSIONS: The MTD for intraperitoneal carboplatin administered as IPHC
      was established at 1000 mg/m(2). IPHC at the initial cytoreductive procedure did
      not preclude subsequent systemic chemotherapy. In addition, repetitive IPHC was
      feasible at second look reassessment surgery.

PMID- 17498783
TI  - Preoperative lymph-vascular space invasion is associated with nodal metastases in
      women with early-stage cervical cancer.
AB  - OBJECTIVE: To determine the association between findings on review of
      preoperative biopsy specimens and the risk of lymph node involvement (LNI) at
      radical hysterectomy in patients with early-stage cervical cancer. METHODS:
      Eighty-one patients were included in this retrospective review. Preoperative
      biopsy features evaluated were stage, grade, histologic subtype, lymph-vascular
      space invasion (LVSI), and depth (>4 mm) of invasion. RESULTS: Twelve patients
      (14.8%) had LNI at radical hysterectomy. Stage, grade, and histologic subtype
      were not associated with LNI. LVSI and depth of invasion >4 mm were both
      significantly associated with LNI (25.6% vs. 4.8%, P=0.01, and 25.0% vs. 4.5%,
      P=0.01, respectively). LVSI with >4 mm invasion was 6.6 times more likely to have
      LNI at the time of radical hysterectomy (RR=6.6; 95% confidence interval, 2.1
      21.9). CONCLUSION: Patients with preoperative LVSI are at higher risk for LNI at
      radical hysterectomy and should be counseled regarding potential implications for
      management.

PMID- 17498784
TI  - B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125
      expression.
AB  - OBJECTIVE: This study characterizes the expression of the novel biomarker B7-H4
      in ovarian cancer tissue, normal ovaries, and benign ovarian tumors, and
      evaluates its relationship to CA125. METHODS: Ovarian tissue lysates from 251
      patients with ovarian carcinoma were assessed for the levels of B7-H4 and CA125
      by ELISA assays. For comparison, ovarian tissues from patients with benign
      ovarian tumors (n=43) and patients with normal ovaries (n=32) were tested. The
      marker concentrations were correlated with CA125 expression, clinicopathological
      variables, and patient outcome. RESULTS: Using a cut-off based on the 95th
      percentile of B7-H4 or CA125 concentration in the control group, B7-H4 was over
      expressed in 48% of patients with stage I cancer, 55% of patients with stage II
      cancer, and 67% of patients with late stage cancer. CA125 was elevated in 31%
      patients with early stage cancer. B7-H4 was elevated in tumors of 30 patients
      with early stage cancer that were negative for CA125. The combination of B7-H4
      and CA125 identified 56 early stage cancer patients (65%) as positive.
      Correlation of marker expression to clinical outcome showed that high B7-H4
      levels were correlated with poor prognosis. However, the effect was not
      significant when outcome was adjusted for other clinicopathological variables.
      CONCLUSION: B7-H4 expression was low in normal ovaries and in benign tumors while
      half of early stage and two-thirds of late stage cancers over-expressed B7-H4.
      The data are consistent with previous observations and support further
      investigation of B7-H4 in the detection of early stage ovarian cancer either
      alone, or in combination with CA125.

PMID- 17498785
TI  - Impulsivity (delay discounting) for food and cocaine in male and female rats
      selectively bred for high and low saccharin intake.
AB  - Previous research in rats indicates that delay discounting for food, a model of
      impulsivity, predicted the rate of acquisition of cocaine self-administration. In
      other studies, rats bred for high saccharin intake (HiS) acquired cocaine self
      administration at higher rates than those with low saccharin intake (LoS), and
      female (F) rats acquired cocaine self-administration more rapidly than males (M).
      The purpose of this study was to examine a possible connection between
      impulsivity, saccharin intake, and sex by comparing M and F rats from the HiS and
      LoS selectively bred lines on measures of impulsivity; i.e., their rate of delay
      discounting for food or i.v. cocaine infusions. The adjusting delay procedure
      allowed rats access to 2 response levers, and a pellet dispenser or an i.v. drug
      infusion pump. In 4 groups (HiS M, HiS F, LoS M, LoS F) responses under a fixed
      ratio (FR) 1 schedule on one lever resulted in one 45 mg pellet immediately, and
      responses on the other lever resulted in 3 or 6 pellets after a delay. Four
      additional groups received either a small cocaine (0.2, 0.4, or 0.8 mg/kg)
      infusion immediately or a delayed larger infusion (3x the amount of the small
      infusions). The delay to the larger reinforcer began at 6 s and increased or
      decreased by 1 s following responses on the delay or immediate levers,
      respectively. A mean adjusted delay (MAD) was calculated over 30 choice trials
      during each daily 3-hour session, and it was used as a quantitative measure of
      impulsivity. In groups maintained by food, HiS rats were more impulsive (lower
      MADs) than LoS rats, and LoS females were more impulsive than LoS males. There
      were no phenotype or sex differences in delay discounting for cocaine.
      Understanding the relationship between impulsivity and other predictors of drug
      abuse (e.g., sex, saccharin intake) is important in developing prevention and
      treatment strategies.

PMID- 17498786
TI  - Reversal of haloperidol-induced tardive vacuous chewing movements and
      supersensitive somatodendritic serotonergic response by buspirone in rats.
AB  - Tardive dyskinesia (TD), a syndrome of involuntary hyperkinesias in the orofacial
      region that develops in patients chronically treated with neuroleptic agents is a
      major limitation of the therapy. Rats chronically treated with haloperidol
      exhibit vacuous chewing movements (VCMs) with the twitching of facial musculature
      and tongue protrusion. The syndrome is widely used as an animal model of TD.
      Evidence suggests a role of 5-hydroxytryptamine (5-HT; serotonin)-1A receptors in
      the pathogenesis and treatment of TD because repeated administration of
      haloperidol resulted in an increase in the effectiveness of 5-HT-1A receptors
      while drugs with agonist activity at 5-HT-1A receptors could attenuate
      haloperidol-induced VCMs. The present study was designed to test the hypothesis
      that a decrease in the responsiveness of somatodendritic 5-HT-1A receptors by the
      coadministration of buspirone could reverse the induction of VCMs and
      supersensitivity at 5-HT-1A receptors by haloperidol. Rats treated with
      haloperidol at a dose of 1 mg/kg twice a day for 2 weeks displayed VCMs with
      twitching of facial musculature that increased in a time dependent manner as the
      treatment continued to 5 weeks. Coadministration of buspirone attenuated
      haloperidol-induced VCMs after 2 weeks and completely prevented it after 5 weeks.
      The intensity of 8-hydroxy-2-di (n-propylamino) tetralin (8-OH-DPAT)-induced
      locomotion was greater in saline+haloperidol injected animals but not in
      buspirone+haloperidol injected animals. 8-OH-DPAT-induced decreases of 5-HT
      metabolism were greater in saline+haloperidol injected animals but not in
      buspirone+haloperidol injected animals. It is suggested that an impaired
      somatodendritic 5-HT-1A receptor dependent response is a major contributing
      factor in the pathophysiology of TD and a normalization of the somatodendritic
      response by drugs may help extending therapeutics in schizophrenia.

PMID- 17498787
TI  - Reduced exhaled nitric oxide values in children with asthma after inpatient
      rehabilitation at high altitude.

PMID- 17498788
TI  - Adiponectin polymorphisms, cord blood levels of adiponectin, and body
      composition.

PMID- 17498790
TI  - Association between IgE levels and asthma severity among African American,
      Mexican, and Puerto Rican patients with asthma.
AB  - BACKGROUND: High levels of IgE are associated with asthma. Whether higher levels
      of IgE are associated with more severe asthma is still unclear. OBJECTIVE: To
      determine whether IgE is associated with asthma severity among Latino and African
      American subjects with asthma. METHODS: We assessed lung function and asthma
      severity among African American, Mexican, and Puerto Rican patients with asthma
      with high IgE levels (> or =100 IU/mL; n = 492) and compared these values to
      those of patients with asthma with low IgE levels (<100 IU/mL; n = 247). We also
      examined IgE as a continuous variable among these groups. RESULTS: Patients with
      asthma with high IgE had a lower mean FEV(1) (87.6 +/- 17.1, percent of
      predicted) than patients with asthma with low IgE (91.5 +/- 17.0; P = .031).
      Regardless of race and ethnicity, baseline FEV(1), forced expiratory flow, and
      FEV(1)/forced vital capacity were lower among subjects with high IgE than among
      subjects with low IgE (P = .031, P < .0001, P = .0001, respectively). In
      addition, 54.7% of patients with asthma with high IgE had been previously
      hospitalized, compared with 44.1% of patients with asthma with low IgE (odds
      ratio, 1.33; 95% CI, 1.04-1.71). CONCLUSION: Higher IgE is associated with lower
      baseline lung function and more severe asthma among these populations. CLINICAL
      IMPLICATIONS: Among patients with asthma from 3 ethnically distinct groups, total
      IgE levels are inversely correlated with baseline lung function and asthma
      severity.

PMID- 17498791
TI  - Interactive effect of family history and environmental factors on respiratory
      tract-related morbidity in infancy.
AB  - BACKGROUND: Family and environmental factors affect the development of
      respiratory morbidity. How these factors interact is unclear. OBJECTIVE: We
      sought to clarify the interactive effect of family history of asthma and
      environmental factors on the occurrence of respiratory morbidity. METHODS: Two
      hundred twenty-one infants with a positive family history of asthma (PFH) and 308
      with a negative family history of asthma (NFH) were prenatally selected and
      followed until the age of 2 years. Exposure to environmental factors and the
      occurrence of respiratory morbidity were recorded. By using multiple logistic
      regression analysis, increased risk was expressed in odds ratios (ORs) adjusted
      for relevant covariables. RESULTS: Infants with a PFH had more respiratory
      morbidity than infants with an NFH. Adjusted ORs ranged from 1.7 (95% CI, 1.0
      2.8) for expiratory wheezing to 4.9 (95% CI, 1.7-13.6) for croup. Parental
      smoking increased the OR of a PFH for wheezing ever (OR, 5.8 [95% CI, 2.5-13.8])
      and attacks of wheezing (OR, 6.8 [95% CI, 2.7-16.9]), as did Der p 1 (OR, 10.2
      [95% CI, 2.8-36.3] and OR, 7.1 [95% CI, 7.1-21.0], respectively). Exposure to
      both parental smoking and Der p 1 further increased this OR (OR, 30.8 [95%, CI,
      6.9-137.2] and OR, 26.2 [95% CI, 5.9-115.6], respectively). Breast-feeding
      decreased the ORs of PFH for tonsillitis and acute otitis media: the increased
      ORs for these diagnoses in formula-fed infants with PFHs versus those with NFHs
      (OR, 9.2 [95% CI, 2.1-39.7] and OR, 2.9 [95% CI, 1.1-7.2], respectively) was
      attenuated in breast-fed infants (OR, 1.8 [95% CI, 0.8-3.8] and OR, 0.7 [95% CI,
      0.4-1.3]). CONCLUSION: Parental smoking and Der p 1 increase the effect of a PFH
      on respiratory morbidity. Breast-feeding reduces this effect. CLINICAL
      IMPLICATIONS: Extra attention should be given to stimulate mothers to breast-feed
      their children in case they cannot stop smoking or taking sanitation measures.

PMID- 17498792
TI  - Rapid systemic uptake of allergens through the respiratory mucosa.

PMID- 17498793
TI  - The role of the veterinarian in bovine fertility management on modern dairy
      farms.
AB  - The decline in dairy herd fertility internationally has highlighted the limited
      impact of traditional veterinary approaches to herd fertility. The role of the
      veterinarian in fertility management on dairy farms has evolved from addressing
      individual clinical conditions to analyzing suboptimal herd metrics. However,
      this paradigm shift has only successfully occurred in some dairy industries and
      less so in others. Needs analyses indicate that the critical constraints to
      change are veterinary practice size, client motivation and data quality and
      availability. In addition, this review identified the inability of veterinarians
      to demonstrate and to market the cost-benefit of their fertility management
      services as important impediments to change. In many cases change is not being
      managed but is imposed by the growth of paraprofessionals. Some veterinarians
      still see their role as an animal clinician while others have evolved into
      leaders of the herd fertility management team. The core role of dairy
      veterinarians remains individual animal examinations but this must be
      supplemented with systematic herd fertility investigation and veterinarian-led
      herd fertility management. This new role encompasses leading the change from
      clinical calls only to a planned approach to herd fertility, demonstrating the
      cost-benefits of the program, scheduling fertility management consultations,
      assisting the farmer in setting specific, measurable, attainable, relevant and
      time-limited (SMART) goals, drawing up standard operating procedures (SOPs),
      training and auditing staff in fertility management practices, encouraging a team
      approach, implementing veterinary fertility management and monitoring
      performance. Veterinarians who fail to engage in this process of change risk
      being marginalized by others keen to promote their herd fertility services.

PMID- 17498794
TI  - Using the canine genome to cure cancer and other diseases.
AB  - A high-quality draft genome sequence of the domestic dog (Canis familiaris),
      together with a dense map of single nucleotide polymorphisms, has been reported.
      Such new tools offer scientists amazing opportunities to define genetic,
      nutritional, environmental, and other risk factors for various canine diseases.
      Because many of the diseases that affect man's best friend also affect us,
      understanding a dog's disease may lead to new preventions and therapies for
      diseases that affect both dogs and people. Since a dog's life span is shorter
      than that for a human, monitoring potential risk factors in a well-controlled
      population of dogs is possible. Such a population should be one where dogs live
      in close relationship with their owners. Although longitudinal studies have been
      previously conducted on animals housed in laboratory environments, the natural
      environment offers a chance to study dogs in environments shared by their owners.
      If dogs are carefully monitored, and select exposures defined, considerable
      information could be collected in a dog's lifetime--the next 10-20 years. Such
      information could hold the clues for important discoveries, including causes and
      cures for cancer.

PMID- 17498795
TI  - Preliminary assessment of reproductive technologies in wood bison (Bison bison
      athabascae): implications for preserving genetic diversity.
AB  - Since the high prevalence of bovine tuberculosis and brucellosis in free-ranging
      wood bison in the Canadian north poses a threat to nearby healthy bison
      populations, commercial bison and cattle ranches, and potentially to humans,
      there is considerable impetus to salvage the genetics of infected bison and
      maintain a disease-free herd. In that regard, there is a great need to develop
      appropriate reproductive technologies. Therefore, the objective of this study was
      to develop protocols to produce and cryopreserve wood bison embryos (based on
      protocols used for cattle). Cumulus oocyte complexes (COC) aspirated from ovaries
      recovered after slaughter were matured in vitro, and fertilized with either
      frozen-thawed semen or chilled epididymal spermatozoa. Although both sources of
      spermatozoa resulted in acceptable rates of fertilization (64.4%, n=45; 89.2%,
      n=28, respectively) and cleavage (75.0%, n=40; 92.5%, n=40), production of
      morulae (7.5%, n=40; 25.0%, n=40) and blastocysts (7.5%, n=40; 10.0%, n=40) was
      low. Morulae- and blastocyst-stage embryos were frozen-stored by vitrification.
      To our knowledge, this is the first report regarding the in vitro production and
      cryopreservation of bison embryos for genetic recovery of diseased wood bison.
      These techniques have substantial potential for conserving and managing the
      genetic diversity of wild bison, and may also have important management
      implications for genetic salvage of diseased bison populations in North America.

PMID- 17498796
TI  - Snus--what should the public-health response be?

PMID- 17498797
TI  - Oral use of Swedish moist snuff (snus) and risk for cancer of the mouth, lung,
      and pancreas in male construction workers: a retrospective cohort study.
AB  - BACKGROUND: Although classified as carcinogenic, snuff is used increasingly in
      several populations. Scandinavian moist snuff (snus) has been proposed as a less
      harmful alternative to smoking, but precise data on the independent associations
      of snus use with site-specific cancers are sparse. We aimed to assess the risks
      for cancer of the oral cavity, lung, and pancreas. METHODS: Detailed information
      about tobacco smoking and snus use was obtained from 279 897 male Swedish
      construction workers in 1978-92. Complete follow-up until end of 2004 was
      accomplished through links with population and health registers. To distinguish
      possible effects of snus from those of smoking, we focused on 125 576 workers who
      were reported to be never-smokers at entry. Adjusted relative risks were derived
      from Cox proportional hazards regression models. FINDINGS: 60 cases of oral, 154
      of lung, and 83 of pancreatic cancer were recorded in never-smokers. Snus use was
      independently associated with increased risk of pancreatic cancer (relative risk
      for ever-users of snus 2.0; 95% CI 1.2-3.3, compared with never-users of any
      tobacco), but was unrelated to incidence of oral (0.8, 95% CI 0.4-1.7) and lung
      cancer (0.8, 0.5-1.3). INTERPRETATION: Use of Swedish snus should be added to the
      list of tentative risk factors for pancreatic cancer. We were unable to confirm
      any excess of oral or lung cancer in snus users.

PMID- 17498798
TI  - Assessment of Swedish snus for tobacco harm reduction: an epidemiological
      modelling study.
AB  - BACKGROUND: Swedish snus is a smokeless tobacco product that has been suggested
      as a tobacco harm reduction product. Our aim was to assess the potential
      population health effects of snus. METHODS: We assessed the potential population
      health effects of snus in Australia with multistate life tables to estimate the
      difference in health-adjusted life expectancy between people who have never been
      smokers and various trajectories of tobacco use, including switching from smoking
      to snus use; and the potential for net population-level harm given different
      rates of snus uptake by current smokers, ex-smokers, and people who have never
      smoked. FINDINGS: There was little difference in health-adjusted life expectancy
      between smokers who quit all tobacco and smokers who switch to snus (difference
      of 0.1-0.3 years for men and 0.1-0.4 years for women). For net harm to occur, 14
      25 ex-smokers would have to start using snus to offset the health gain from every
      smoker who switched to snus rather than continuing to smoke. Likewise, 14-25
      people who have never smoked would need to start using snus to offset the health
      gain from every new tobacco user who used snus rather than smoking.
      INTERPRETATION: Current smokers who switch to using snus rather than continuing
      to smoke can realise substantial health gains. Snus could produce a net benefit
      to health at the population level if it is adopted in sufficient numbers by
      inveterate smokers. Relaxing current restrictions on the sale of snus is more
      likely to produce a net benefit than harm, with the size of the benefit dependent
      on how many inveterate smokers switch to snus.

PMID- 17498799
TI  - Anabolic effects of bisphosphonates on peri-implant bone stock.
AB  - The long-term durability of total joint replacements is critically dependent on
      adequate peri-implant bone stock, which can be compromised by wear debris
      mediated osteolysis. This study investigated the effects of bisphosphonates on
      enhancing peri-implant bone in the presence of clinically relevant ultra-high
      molecular weight polyethylene (UHMWPE) wear debris. Fiber-mesh coated titanium
      alloy plugs were implanted bilaterally in the femoral condyles of 36 New Zealand
      white rabbits. Implants in the left femora were covered with submicron UHMWPE
      particles during surgery. Rabbits were administered either no drug, subcutaneous
      alendronate weekly (1.0mg/kg/week) or a single dose of intravenous zoledronate
      (0.015mg/kg). A total of 6/12 rabbits in each group were sacrificed at 6 weeks
      and the remainder at 12 weeks postoperatively. Peri-implant bone stock was
      analyzed radiographically and histomorphometrically. Radiographically, both
      bisphosphonates significantly increased periprosthetic cortical thickness at 6
      weeks (p<0.0001; alendronate: +18%; zoledronate: +11%) and at 12 weeks (p=0.001;
      alendronate: +17%; zoledronate:+19%). Histomorphometrically, alendronate and
      zoledronate raised peri-implant bone volume (BV/TV) up to 2-fold after 6 weeks
      without added wear debris and more than 3-fold when wear debris was present.
      Furthermore a 6-week bisphosphonate treatment increased osteoid thickness in the
      absence of wear debris (alendronate: +132%, p=0.007; zoledronate: +67%, p=0.51)
      and in the presence of wear debris (alendronate: +134%, p=0.023; zoledronate:
      +138%, p=0.016). In summary, alendronate and zoledronate treatment increased
      periprosthetic bone stock in a rabbit femoral model, particularly in the presence
      of UHMWPE wear debris. These new findings suggest that bisphosphonates may more
      than compensate for the well-documented negative effects of wear debris on peri
      implant bone stock. The combined antiresorptive and osteoanabolic effects of
      bisphosphonates on periprosthetic bone stock may have an important role for
      critically improving the biological fixation and ultimate durability of total
      joint arthroplasty.

PMID- 17498800
TI  - Characterization of virus/double-stranded RNA-dependent induction of
      antimicrobial peptide hepcidin in trout macrophages.
AB  - Hepcidin is an antimicrobial peptide responsive to bacterial infection. We report
      the characterization of a virus/double-stranded RNA (dsRNA) induction of hepcidin
      in rainbow trout (Oncorhynchus mykiss). Increased level of hepcidin mRNA was
      observed in trout macrophage RTS11 cells treated with polyinosinic-polycytidylic
      acid (poly I:C), a mimic of viral dsRNA. The induction was also observed in poly
      I:C-injected trout, demonstrating that it is a bona fide biological response. The
      induction was not observed in livers or hepatic RTH1B2C cells despite the
      presence of IFN response. The induction required de novo protein synthesis.
      Studies on the kinetic relationship among the poly I:C-regulated hepcidin
      induction and IFN response indicated that the two responses were uncoupled.
      Interestingly, in RTS11 infected with infectious hematopoietic necrosis virus,
      the level of hepcidin was increased as expected but subsequently reduced to below
      baseline as the infection progressed, whereas IFNs, Mx1 and TLR3 were still
      increasing.

PMID- 17498801
TI  - Identification and characterization of tumor antigens by using antibody phage
      display and intrabody strategies.
AB  - To generate a panel of antibodies binding human breast cancers, a human single
      chain Fv phage display library was selected for rapid internalization into the SK
      BR-3 breast cancer cell line. Thirteen unique antibodies were identified within
      the 55 cell binding antibodies studied, all of them showing specific staining of
      tumor cells compare to normal epithelial cells. Two of the antibodies bound the
      ErbB2 oncogene while 6 bound the tumor marker transferrin receptor (TfR). By
      developing a scFv immunoprecipitation method, we were able to use LC-MS/MS to
      identify the antigen bound by one of the antibodies (3GA5) as FPRP (prostaglandin
      F2alpha receptor-regulatory protein)/EWI-F/CD9P-1 (CD9 partner 1) an Ig
      superfamily member that has been described to interact directly with CD9 and CD81
      tetraspanins and to be overexpressed in adherent cancer cell lines. Although the
      3GA5 scFv had no direct anti-proliferative effect, intracellular expression of
      the scFv was able to knockdown CD9P-1 expression and could be used to further
      define the role of the tetraspanin system in proliferation and metastasis.
      Moreover, the 3GA5 scFv was rapidly internalized into breast tumor cells and
      could have potential for the targeted delivery of cytotoxic agents to breast
      cancers. This study is the proof of principle that the direct selection of phage
      antibody libraries on tumor cells can effectively lead to the identification and
      functional characterization of relevant tumor markers.

PMID- 17498802
TI  - An extra molecule in addition to human tapasin is required for surface expression
      of beta2m linked HLA-B4402 on murine cell.
AB  - Murine MHC class I can be readily expressed on the surface of human cell lines,
      but human class I molecules are expressed on mouse cells at a reduced level. Both
      human beta-2-microglobulin (beta(2)m) and tapasin (Tpn) have been demonstrated to
      be required for proper human MHC class I surface expression. Here we report that
      besides beta(2)m and tapasin, an extra unidentified component is also critical
      for the expression of certain human class I alleles. By covalently linking HLA
      B4402 heavy chain to beta(2)m (beta(2)m-B44) a pre-assembled class I molecule has
      been created, which can be efficiently expressed and travel to the surface in
      human cells. In spite of being able to express inside cells, the linked beta(2)m
      B44 molecule does not express on the surface of a murine fibroblast. Further
      investigation shows that lack of appearance on the surface is not due to quick
      degradation of unloaded class I, since provision of HLA-B4402 binding peptide
      could not rescue impaired surface expression. Co-expression with human tapasin
      does not rescue the defect excluding tapasin as the critical component for
      expression and indicating that a novel component of human origin is required for
      efficient surface expression of beta(2)m-B44 in murine cells. Surprisingly, not
      only did the beta(2)m-B44 construct fail to express on murine cells but also the
      surface expression of native murine MHC class I Kb was greatly reduced in
      transfected cells. It is likely that the expressed linked chain competitively
      associates with a component of class I processing in murine cells, reducing the
      exit rate of assembled mouse class I molecules. The results together suggest an
      unknown mechanism, which leads to the trapping of class I molecules in the ER.

PMID- 17498803
TI  - Molecular cloning and characterization of a thioester-containing protein from
      Zhikong scallop Chlamys farreri.
AB  - Thioester-containing proteins are a family of proteins characterized by the
      unique intrachain beta-cysteinyl-gamma-glutamyl thioester, which play important
      roles in innate immune responses. The cDNA of Zhikong scallop Chlamys farreri
      thioester-containing protein (designated as CfTEP) was cloned by expressed
      sequence tag (EST) and rapid amplification of cDNA ends (RACE) approaches. The
      full-length cDNA of CfTEP was of 4616 bp, consisting of a 5'-terminal
      untranslated region (UTR) of 30 bp and a 3'UTR of 140 bp with a polyadenylation
      signal sequence AATAAA and a poly(A) tail. The CfTEP cDNA encoded a polypeptide
      of 1481 amino acids with the theoretical isoelectric point of 5.98 and the
      predicted molecular weight of 161.4 kDa. The deduced amino acid sequence of CfTEP
      contained the canonical thioester motif GCGEQ, nine potential N-glycosylation
      sites and a C-terminal distinctive cysteine signature. It also contained a
      presumed catalytic histidine and proteolytic cleavage sites that were similar to
      C3 molecules. The high similarity of CfTEP with the thioester-containing proteins
      in other organisms, such as the TEPs from insects, the complement component C3,
      C4, C5 and the protease inhibitor alpha(2)-macroglobulin indicated that CfTEP
      should be a member of TEP family. The phylogenetic analysis revealed that CfTEP
      was closely related to TEPs from mollusc, nematodes and insects, and they formed
      a separate branch apart from the branches of complements factors and alpha(2)
      macroglobulins. The spatial expression of CfTEP transcripts in healthy and
      bacterial challenged scallops was examined by semi-quantitative RT-PCR. The CfTEP
      transcripts were mainly detected in the tissues of hepatopancreas and gonad, and
      remarkably up-regulated by microbial challenge, which suggested that CfTEP was a
      constitutive and inducible acute-phase protein involved in immune defense. These
      results provided new insights into the role of CfTEP in scallop immune responses,
      as well as the evolutionary origin of this important, widespread and functionally
      diversified family of proteins.

PMID- 17498804
TI  - A new classification of calcification of intraocular lenses.
AB  - OBJECTIVE: To define and classify the major types of intraocular lens (IOL)
      calcification. DESIGN: Retrospective observational case series with
      clinicopathologic correlation. PARTICIPANTS: More than 400 IOLs explanted because
      of opacification. METHODS: The authors reviewed the clinical information and
      histologic findings of all IOLs that had been explanted because of opacification
      or calcification of the IOLs accessioned in their laboratory between January 1999
      and December 2004. MAIN OUTCOME MEASURE: The proposed mechanism that led to
      calcification of each IOL design. RESULTS: Three major types of calcification
      were identified: (1) primary calcification, (2) secondary calcification, and (3)
      false-positive calcification or pseudocalcification. The primary form refers to
      calcification that is inherent in the IOL, that is, is based on possible
      inadequate formulation of the polymer, fabrication of the IOL, or issues with its
      packaging process. The calcification presumably occurs in otherwise normal eyes
      and generally is not associated with preexisting diseases. The secondary form
      refers to deposition of calcium onto the surface of the IOL most likely the
      result of environmental circumstances (e.g., changes in the aqueous milieu
      surrounding the implanted IOL associated with preexisting or concurrent diseases
      or indeed any condition that has disrupted the blood-aqueous barrier). By
      definition, it is not related to any problem with the IOL itself. The false
      positive or pseudocalcification refers to those cases in which other pathology is
      mistaken for calcification or false-positive staining for calcium occurs.
      CONCLUSIONS: When evaluating the pathogenesis and nature of IOL calcification in
      or on any given design, one should categorize it according to these types.
      Primary calcification is IOL related and the IOL should be withdrawn or modified
      to correct the problem. After the cause is identified and the lens is implanted
      again, patients should be followed up for up to 2 years to be sure the problem is
      alleviated. Secondary calcification is by definition not IOL related; it may
      occur with virtually all IOL designs implanted under various adverse
      circumstances. No IOL, hydrophilic or hydrophobic, is immune to secondary
      calcification. The false-positive form is recognized readily in the laboratory
      and this erroneous diagnosis is avoided.

PMID- 17498805
TI  - Incidence of uveal melanoma in Europe.
AB  - PURPOSE: To estimate incidence rates of uveal melanoma in Europe from 1983 to
      1994. DESIGN: Incidence analysis of data from cancer registries adhering to the
      European Cancer Registry-based study on survival and care of cancer patients
      (EUROCARE) (cases diagnosed from 1983 to 1994). PARTICIPANTS: Data of 6673
      patients with ocular melanoma (as defined by International Classification of
      Diseases for Oncology morphology codes 8720 to 8780 [melanoma] and International
      Classification of Diseases 9 (ICD9) codes 190.0 [iris and ciliary body], 190.5
      [retina], 190.6 [choroid], and 190.9 [unspecified ocular location]) from 33
      cancer registries of 16 European countries. METHODS: Incidence rate ratios (IRRs)
      were obtained from a multilevel Poisson regression model. MAIN OUTCOME MEASURES:
      Incidence rates and IRRs associated with demographic and geographic variables.
      RESULTS: Standardized incidence rates increased from south to north across
      registries, from a minimum of <2 per million in registries of Spain and southern
      Italy up to >8 per million in Norway and Denmark. The inclusion of tumors with
      unspecified ocular location (code 190.9) increased incidence rates in most United
      Kingdom registries, but not in the other geographic areas, where this code was
      seldom used for uveal melanomas. Incidence increased noticeably up to age 55
      (IRR, 1.46 per 5 years; 95% confidence interval [CI], 1.36-1.57) but leveled off
      after age 75 (IRR, 0.99 per 5 years; 95% CI, 0.93-1.05), with intermediate levels
      midway (IRR, 1.18 per 5 years; 95% CI, 1.12-1.23). It was also higher in males
      (IRR, 1.22; 95% CI, 1.16-1.28). Rates were stable during the study period, but a
      cohort effect was evidenced, accounting for higher incidence rates in people born
      during the period 1910 to 1935 (P = 0.005). Incidence increased with latitude (P
      = 0.008), which explained most differences in rates among areas. CONCLUSIONS: In
      this large series of uveal melanomas, we found stable incidence during the years
      1983 to 1994. The north-to-south decreasing gradient supports the protective role
      of ocular pigmentation. European ophthalmologists should develop guidelines to
      standardize the coding of tumors treated conservatively using the ICD
      classification to improve the registration and surveillance of uveal melanoma by
      cancer registries.

PMID- 17498806
TI  - Resveratrol attenuates oxidative-induced DNA damage in C6 Glioma cells.
AB  - The antioxidant compound, trans-resveratrol, is found in substantial amounts in
      several types of red wine and has been proposed to have beneficial effects in
      brain pathologies that may involve oxidative stress. The objective of the present
      study was to investigate the genoprotective effects of resveratrol under
      conditions of oxidative stress induced by hydrogen peroxide in C6 glioma cells.
      DNA damage was assessed by the alkaline single-cell gel electrophoresis assay or
      comet assay. In order to investigate the genoprotective effects of resveratrol
      against oxidative stress induced by hydrogen peroxide on DNA damage, two models
      of oxidative stress induction were utilized. (I) 1mM hydrogen peroxide for 0.5h
      (10-250 microM of resveratrol) and (II) 0.1 or 0.5mM hydrogen peroxide for 6h (10
      100 microM of resveratrol). Resveratrol was able to prevent oxidative damage to
      cellular DNA, induced in model I, at all concentrations tested; however, at 6h of
      incubation, resveratrol prevented DNA damage only partially. After 6h of
      incubation (up to 48h) resveratrol per se induced a slight time and dose
      dependent DNA damage. In conclusion, these results provide evidence that
      resveratrol may act as a significantly bioactive compound, supporting the
      possibility that, due to its antioxidant properties, it may be important in
      health and disease for protecting against DNA damage through oxidative stress.

PMID- 17498807
TI  - Current trends in shape and texture analysis in neurology: aspects of the
      morphological substrate of volume and wiring transmission.
AB  - Morphological and morphometrical studies of neural shape and texture are becoming
      more and more important in the field of neurosciences due to the recognized close
      link between shape and function at molecular, cellular and tissutal level.
      Indeed, some different morphological classes of neurons are known to be
      correlated to well defined functional classes; several neurological pathologies
      are associated with modification of neuronal shape; during a neural development,
      cells impose geometrical and physical constrains at one another. The
      understanding of these fundamental processes requires
      morphological/morphometrical analysis. In addition, the geometric properties at
      the individual level plays a relevant role in defining the actual and the
      potential global connectivity of the system. From this standpoint it will be
      important to study the relationship between the shape descriptors illustrated in
      this paper and the potential global connectivity of the system. In such a
      context, the classical multivariate statistical tools of analysis (and probably
      new ones) will become necessary to correctly utilize huge set of information
      provided from shape and texture descriptors. In this review, avoiding to consider
      some common measures of shape, such as area, perimeter, perimeter/area ratio,
      eccentricity, we considered only shape and texture analysis methods classified
      within the set of scalar transform techniques, discussing their advantages and
      limitations, especially regarding their application to neuromorphometry.

PMID- 17498808
TI  - Extracting the basal extracellular dopamine concentrations from the evoked
      responses: re-analysis of the dopamine kinetics.
AB  - Fast-scan cyclic voltammetry in conjunction with carbon fiber microelectrode has
      been used to study dopamine (DA) release and uptake mechanisms in rat brains
      because of the smaller size of the electrode and the subsecond resolution.
      Current voltammetry data were analyzed by a DA kinetic model assuming a zero
      baseline, which is in conflict with existing microdialysis findings and a recent
      claim of the striatal extracellular DA concentration at micromolar levels. This
      work applied a new analysis approach based on a modified DA kinetic model to
      analyze the kinetics of electrically evoked DA overflow in the caudate-putamen of
      anesthetized rats. The DA uptake parameters were fitted from the electrical
      stimulation phase, and subsequently used to calculate theoretical DA uptake
      rates. Comparison of the theoretical uptake rates with experimental clearance
      rates allows for the study of the tonic DA release process following electrical
      stimulations. Analyses of DA voltammetry data suggest that the locally averaged
      basal level of extracellular DA in the rat striatum might be confined between 95
      and 220 nM. The disparate time scales in the clearance kinetics of endogenous and
      exogenous DA were investigated. Long-distance diffusion could only partially
      explain the slow clearance time course of exogenous DA. Model simulations and
      parameter analyses on evoked DA responses indicate that suppression of the
      nonevoked DA release process immediately following electrical stimulation cannot
      completely account for the rapid clearance of the electrically evoked DA.
      Inconsistency in the measured uptake strengths in the literature studying
      endogenous and exogenous DA remains to be investigated in the future.

PMID- 17498809
TI  - A beam-walking apparatus to assess behavioural impairments in MPTP-treated mice:
      pharmacological validation with R-(-)-deprenyl.
AB  - A beam-walking apparatus has been evaluated for its ability to detect motor
      impairments in mice acutely treated with the dopaminergic neurotoxin 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg, s.c., single or double
      administration). Mice subjected to MPTP lesioning showed deficits in motor
      performance on the beam-walking task, for up to 6 days post-MPTP administration,
      as compared to saline-treated controls. In addition, MPTP-treated mice were
      detected to have a marked depletion in striatal dopamine levels and a concomitant
      reduction in substantia nigra (SN) tyrosine hydroxylase (TH) immunoreactivity, at
      7 days post-MPTP administration, indicative of dopaminergic neuronal loss. Pre
      administration of the potent MAO-B inhibitor R-(-)-deprenyl at 3 or 10 mg/kg, 30
      min, s.c, significantly inhibited the MPTP-induced reduction in SN TH
      immunoreactivity, striatal dopamine depletions and impairments in mouse motor
      function. The data described in the present study provides further evidence that
      functional deficits following an acute MPTP dosing schedule in mice can be
      quantified and are related to nigro-striatal dopamine function.

PMID- 17498810
TI  - Characterization of rat rostral raphe primary cultures: multiplex quantification
      of serotonergic markers.
AB  - Previous reports establishing raphe cultures typically yield less than 1%
      serotonin (5-HT)-positive neurons and are impractical for transcriptional
      studies. In this study, we have established primary cultures enriched in 5-HT
      neurons and quantified the proportion of cells expressing serotonergic and non
      serotonergic markers. We have also shown the feasibility of using the multiplex
      real-time PCR technique to measure the relative amounts of RNA for some of these
      markers. Rostral raphe cells derived from E13-15 rat embryos were cultured for 7
      days and analyzed by quantitative immunofluorescence and western blot analysis.
      In these cultures, approximately 8% of neurons were immunopositive for
      serotonergic markers (5-HT or tryptophan hydroxylase (TPH)). The percentage of
      cells labeled for GFAP (glial marker), tyrosine hydroxylase (catecholaminergic),
      and GAD65/67 (GABAergic) was 5, 1, and 54%, respectively. Transcription factors
      REST/NRSF and Deaf-1 were present in 9 and 98% of cells, respectively. Multiplex
      quantitative RT-PCR (Q-PCR) analysis was done for TPH2, 5-HT1A receptor or Deaf-1
      RNAs paired with GAPDH RNA as control. Using this approach, standard curves for
      each RNA were obtained over 200-fold concentration range of dilution with r2
      values >0.99. The relative abundances determined by Q-PCR are consistent with the
      expression of TPH2>Deaf-1>5-HT1A receptor RNA in serotonergic raphe cells. The
      standard error of TPH2 RNA levels between cultures was <20%, indicating a
      consistent purity of 5-HT neurons. Thus, we have generated a highly consistent
      and reproducible model system that is enriched in 5-HT neurons and that will be
      valuable in future investigation of serotonergic regulation.

PMID- 17498811
TI  - Design and validation of a MR-compatible pneumatic manipulandum.
AB  - The combination of functional MR imaging and novel robotic tools may provide
      unique opportunities to probe the neural systems underlying motor control and
      learning. Here, we describe the design and validation of a MR-compatible, 1
      degree-of-freedom pneumatic manipulandum along with experiments demonstrating its
      safety and efficacy. We first validated the robot's ability to apply computer
      controlled loads about the wrist, demonstrating that it possesses sufficient
      bandwidth to simulate torsional spring-like loads during point-to-point flexion
      movements. Next, we verified the MR-compatibility of the device by imaging a head
      phantom during robot operation. We observed no systematic differences in two
      measures of MRI signal quality (signal/noise and field homogeneity) when the
      robot was introduced into the scanner environment. Likewise, measurements of
      joint angle and actuator pressure were not adversely affected by scanning.
      Finally, we verified device efficacy by scanning 20 healthy human subjects
      performing rapid wrist flexions against a wide range of spring-like loads. We
      observed a linear relationship between joint torque at peak movement extent and
      perturbation magnitude, thus demonstrating the robot's ability to simulate spring
      like loads in situ. fMRI revealed task-related activation in regions known to
      contribute to the control of movement including the left primary sensorimotor
      cortex and right cerebellum.

PMID- 17498812
TI  - Weight change in the acute treatment of bipolar I disorder: a naturalistic
      observational study of psychiatric inpatients.
AB  - BACKGROUND: Bipolar patients have increased prevalence rates of overweight and
      obesity compared with the general population. Recent increases in the use of
      atypical antipsychotics and combination therapies have led to growing concern
      about obesity and metabolic disturbances. We therefore evaluated weight change
      and its correlates during the treatment of acute mania in a closed-ward hospital
      setting. METHODS: We evaluated weight change over 4 weeks in 179 consecutive
      patients with bipolar I disorder presenting with acute manic symptoms. RESULTS:
      Overall weight change was +2.7+/-3.0 kg (+4.6+/-5.2%). Whereas 24.6% of patients
      were obese at baseline, 36.3% were obese after 4 weeks. Duration of illness was
      correlated with weight change, but its effect was not robust. Baseline
      weight/BMI, sex, age of onset, and history of previous medication were not
      significantly correlated with weight changes. Patients prescribed olanzapine plus
      valproate showed the largest increase in weight (3.8+/-2.9 kg). Overall, patients
      on any kind of atypical antipsychotics showed greater weight gain than those on
      typical antipsychotics or without antipsychotics. Combination treatment with
      antipsychotics and mood stabilizer resulted in greater weight gain than
      monotherapy with an antipsychotic or mood stabilizer. LIMITATIONS: The short-term
      assessment (4 weeks) of weight change and the lack of variables previously
      reported to be related to weight gain, such as number of depressive episodes,
      warrant caution in the interpretation of our results. CONCLUSIONS: Even during
      short period of acute treatment, bipolar patients showed significant weight gain
      and became obese in a closed-ward setting. Clinicians prescribing combination
      therapies should pay more attention to weight gain and obesity.

PMID- 17498814
TI  - Bacillus cereus var. toyoi enhanced systemic immune response in piglets.
AB  - Probiotic bacteria have been suggested to stimulate the host immune system. In
      this study we evaluated the immunomodulatory effects of probiotic Bacillus cereus
      var. toyoi on the systemic immunity of piglets. A pool of 70 piglets was divided
      into a probiotic or control group. We determined the ratios of peripheral blood
      mononuclear cell (PBMC) subsets and measured proliferative responses and cytokine
      production of PBMCs and effects on vaccination responses. Blood samples of
      probiotic-treated piglets showed a significantly lower frequency of
      CD8(high)/CD3+ T cells and CD8(low)/CD3+ T cells and a significant higher
      CD4+/CD8+ ratio. IL-4 and IFN-gamma production of polyclonally stimulated PBMCs
      was on average higher in the probiotic group. Specific proliferative responses of
      PBMCs to Influenza vaccination antigens were significantly higher and antibody
      titers against H3N2 Influenza and Mycoplasma vaccination antigens were on average
      higher in the probiotic group. In conclusion, B. cereus var. toyoi therefore
      alters the immune status of piglets as indicated by changes in the ratios as well
      as functionalities of systemic immune cell populations.

PMID- 17498815
TI  - Tonsillectomy with thermal welding technology using the TLS(2) thermal ligating
      shear.
AB  - OBJECTIVE: To introduce and assess a new method of tonsillectomy with thermal
      welding technology (TWT) using the thermal ligating shear (TLS(2)), in pediatric
      population. METHOD: TWT provides a new surgical instrument that combines heat and
      pressure to simultaneously coagulate and divide tissue. Among the headpieces
      available for the TWT generator, the TLS(2) handpiece was selected. A prospective
      study was conducted in our Department, on 60 children who underwent tonsillectomy
      with the use of TWT. Inclusion criteria were obstructive sleep apnea syndrome,
      peritonsilar abscess history and chronic tonsillitis. Patients undergoing
      adenoidectomy, or any other procedure together with tonsillectomy were excluded
      from this study. All patients' data, including intraoperative blood loss,
      operation time and complication rates were recorded in a database. RESULTS: Our
      series consisted of 60 patients (39 male and 21 female). There was no measurable
      bleeding during surgery in any of the cases. The mean operative time was 20 min.
      Only one case of postoperative hemorrhage occurred. Mild uvula edema was noticed
      in 25 patients. CONCLUSION: TWT is a safe method for tonsillectomy. Among the
      several handpieces available for the TWT generator, the TLS(2) is very effective
      and easy to use in tonsillectomy procedures, providing sufficient heamostasis and
      diminished operative time.

PMID- 17498813
TI  - Cloning and large-scale expansion of epitope-specific equine cytotoxic T
      lymphocytes using an anti-equine CD3 monoclonal antibody and human recombinant IL
      2.
AB  - Cytotoxic T lymphocytes are involved in controlling intracellular pathogens in
      many species, including horses. Particularly, CTL are critical for the control of
      equine infectious anemia virus (EIAV), a lentivirus that infects horses world
      wide. In humans and animal models, CTL clones are valuable for evaluating the
      fine specificity of epitope recognition, and for adoptive immunotherapy against
      infectious and neoplastic diseases. Cloned CTL would be equally useful for
      similar studies in the horse. Here we present the first analysis of a method to
      generate equine CTL clones. Peripheral blood mononuclear cells were obtained from
      an EIAV-infected horse and stimulated with the EIAV Rev-QW11 peptide. Sorted CD8+
      T cells were cloned by limiting dilution, and expanded without further antigen
      addition using irradiated PBMC, anti-equine CD3, and human recombinant IL-2.
      Clones could be frozen and thawed without detrimental effects, and could be
      subsequently expanded to numbers exceeding 2 x 10(9)cells. Flow cytometry of
      expanded clones confirmed the CD3+/CD8+ phenotype, and chromium release assays
      confirmed CTL activity. Finally, sequencing TCR beta chain genes confirmed
      clonality. Our results provide a reliable means to generate large numbers of
      epitope-specific equine CTL clones that are suitable for use in downstream
      applications, including functional assays and adoptive transfer studies.

PMID- 17498816
TI  - Tracheostomy in human immuno-deficiency virus infected children at the Red Cross
      War Memorial Children's Hospital, Cape Town, South Africa.
AB  - Tracheostomy in adults with HIV/AIDS has been reported to be associated with both
      high and early mortality of 47-100%. There is minimal data regarding the role of
      tracheostomy in HIV infected children. We did a retrospective analysis of HIV
      positive children that underwent tracheostomy at our institution over a 5-year
      period, 2002-2006. A total of 70 tracheostomies were done during the period and
      15 (21.4%) of these children were confirmed as HIV infected. The average age at
      presentation for HIV infected children with upper airway obstruction resulting
      eventually in tracheostomy was 9.4 months and 60% were under 1 year of age. Only
      three (20%) were on Anti-Retroviral Therapy (ART) prior to presentation. The
      cause of upper airway obstruction was croup in 14 (93%) of these 15 children.
      Following tracheostomy all were treated with ART. To date six children have been
      successfully decannulated (40%) and there have been three deaths (20%) which were
      unrelated to tracheostomy. CONCLUSION: Tracheostomy in HIV positive children is
      not associated with the high mortality that has been reported in adults provided
      such children are started on treatment with antiretroviral therapy.

PMID- 17498817
TI  - Specific roles of GABA(B(1)) receptor isoforms in cognition.
AB  - The GABA(B) receptor is a heterodimer of GABA(B(1)) and GABA(B(2)) subunits.
      There are two isoforms of the GABA(B(1)) subunit: GABA(B(1a)) and GABA(B(1b)).
      Recent studies with mutant mice suggest a differential role for the two
      GABA(B(1)) isoforms in behavioural processes. As pharmacological and genetic
      studies have implicated GABA(B) receptors in cognition we investigated the
      behaviour of GABA(B(1a))(-/-) and GABA(B(1b))(-/-) mice in different types of
      cognitive paradigms. GABA(B(1a))(-/-) and GABA(B(1b))(-/-) mice were both
      impaired relative to wildtype controls in a continuous spontaneous alternation
      behaviour test of working spatial memory. In contrast to the reported phenotype
      of GABA(B(1))(-/-) mice, however, neither GABA(B(1a))(-/-) nor GABA(B(1b))(-/-)
      mice were deficient in a passive avoidance task. On the other hand, GABA(B(1a))(
      /-) mice were impaired in familiar and novel object recognition. We conclude that
      GABA(B(1)) isoforms contribute differentially to GABA(B) receptor-mediated
      cognitive processes.

PMID- 17498818
TI  - The beta2 adrenergic receptor regulates morphine tolerance and physical
      dependence.
AB  - Adaptations to the chronic administration of opioids reduce the utility of these
      drugs in treating pain and support addiction. Recent genetics-based approaches
      have implicated the beta2 adrenergic receptor (beta2-AR) in controlling some of
      these responses. We do not know, however, whether this receptor can modulate
      tolerance, dependence or changes in gene expression caused by chronic opioid
      administration. For our studies we used C57BL/6 mice and beta2-AR knockout mice
      in the FVB background. Morphine dose-response relationships were established both
      prior to and after chronic morphine treatment. In some cases, the selective beta2
      AR antagonist butoxamine was administered along with or after morphine. Physical
      dependence was assessed using naloxone-precipitated withdrawal. The expression of
      calcitonin gene related peptide (CGRP) and substance P (SP) were measured in
      spinal cord and dorsal root ganglion (DRG) tissues using both real-time PCR and
      enzyme-linked immunoassay (ELISA). Both the co-administration of butoxamine with
      morphine and the administration of butoxamine after chronic morphine reversed
      morphine tolerance. Morphine failed to cause tolerance in beta2-AR knockout mice.
      Physical dependence was reduced under the same circumstances. The chronic
      administration of butoxamine with morphine reduced or eliminated the normally
      observed up-regulation of CGRP and SP in spinal cord and DRG tissues. Our results
      suggest that the beta2-AR modulates both opioid tolerance and physical
      dependence. Activation of beta2-ARs appears to be required for some of the key
      neurochemical changes which characterize chronic opioid administration.
      Therefore, beta2-AR antagonists show some promise as agents to enhance chronic
      opioid analgesic therapy.

PMID- 17498819
TI  - Effects of tributyltin on the immune system of Japanese flounder (Paralichthys
      olivaceus).
AB  - Effects of tributyltin (TBT) which has been used for antifouling paint of ship's
      hulls and fishing nets on the immune system in Japanese flounder (Paralichthys
      olivaceus) were investigated. After short-term exposure to a high level of TBT,
      leucocytes in the head kidney from 1-year-old flounder were examined for the
      proportion of neutrophils in total leucocytes. Also examined were their
      respiratory burst activities using flow cytometry, the reduction of nitroblue
      tetrazolium (NBT) and lysozyme activities. Furthermore, long-term exposures to a
      relatively low level of TBT using young flounder were also carried out. The
      proportion of neutrophils in total leucocytes prepared from head kidney in each
      fish exposed to TBT at 20 microg/L for 5 days and the reduction of NBT by
      leucocytes prepared from the same experimental conditions increase compared to
      the control group. The contents were 42.0+/-6.8 and 52.5+/-6.3%, respectively.
      Significant differences of the NBT reduction were observed between 0 and 20
      microg/L TBT exposure groups. On the other hand, the respiratory burst activity
      of cells in the exposure group clearly showed a tendency to decrease compared to
      the control group. Furthermore, high level of TBT also inhibited lysozyme
      activity which plays an important role for the bacteriocidal procedures. However,
      similar results were not obtained in the exposure group with a relatively low
      level of TBT. To determine the immunotoxic effects of TBT, infection experiments
      using pathogens which are naturally occurring should be further investigated.

PMID- 17498820
TI  - Plasmodium falciparum biosynthesizes sulfoglycosphingolipids.
AB  - Sulfated glycosphingolipids are present on the surface of a variety of cells.
      They are active participants in adhesion processes in many systems and appear to
      be involved in the regulation of cell proliferation, differentiation and other
      developmental cellular events. However, the body of knowledge about synthesis,
      structure, and function of glycolipids in parasitic protozoa is very limited so
      far. In this work, we show by metabolic incorporation of [(14)C]palmitic acid,
      [(14)C]glucose and Na(2)(35)SO(4) that sulfoglycosphingolipids are biosynthesized
      in the three intraerythrocytic stages of Plasmodium falciparum. After
      saponification, purification of the labelled acidic components was achieved and
      two components named SPf1 and SPf2 were characterized. Chemical degradations and
      TLC analysis pointed out to sulfolipidic structures. Analysis by UV-MALDI-TOF
      mass spectrometry in the negative ion mode using nor-harmane as matrix showed for
      SPf2 a structure consisting in a disulfated hexose linked to a 20:1 sphingosine
      acylated with C18:0 fatty acid. Interestingly, parasite treatment with low
      concentrations of d,l-threo-phenyl-2-palmitoylamino-3-morpholino-1-propanol
      (PPMP) caused an arrest on parasite development associated to the inhibition of
      sulfoglycolipid biosynthesis. Taking into account that sulfoglycolipidic
      structures are currently involved in adhesion processes, our findings open the
      possibility to study the participation of this type of structures in the
      described aggregation phenomena in severe malaria and may contribute to clarify
      the pathogenesis of the disease. This report shows for the first time the
      synthesis of sulfoglycolipids in Apicomplexa.

PMID- 17498821
TI  - Human 1A6/DRIM, the homolog of yeast Utp20, functions in the 18S rRNA processing.
AB  - 1A6/DRIM is a nucleolar protein with a nucleolar targeting sequence in its 3'
      terminus. Bioinformatic analysis indicated that human 1A6/DRIM shares 23%
      identity and 43% similarity with yeast Utp20, which has been reported as a
      component of U3 snoRNA protein complex and has been implicated in 18S rRNA
      processing. In the present study, we found, by utilizing RT-PCR with RNA
      extracted from anti-1A6/DRIM immunoprecipitates and Northern blotting, that
      1A6/DRIM is associated with U3 snoRNA. Pulse-chase labeling assays showed that
      silencing of 1A6/DRIM expression in HeLa cells resulted in a delayed 18S rRNA
      processing. Furthermore, immunoprecipitations revealed that 1A6/DRIM was also
      associated with fibrillarin, another U3 RNP component in HeLa cells. These
      results indicate that 1A6/DRIM is involved in 18S rRNA processing and is the bona
      fide mammalian Utp20.

PMID- 17498822
TI  - Cognitive impairment over the age of 85: hospitalization and mortality.
AB  - The risks of cognitive impairment among hospitalized patients over age 85 are not
      adequately understood. We used electronically recorded ICD-9 codes of inpatients
      over 85 years old to identify patients age > or =85 who showed signs of cognitive
      impairment during hospitalization at our institution. We randomly selected
      patient records showing cognitive impairment and patient control records matched
      for age and admission date but without cognitive impairment and obtained
      mortality information up to 18 months after discharge. Records were further
      examined to characterize hospital stay including reason for admission. After
      adjustment for comorbidities and potential confounders, patients over age 85 with
      ICD-9-defined cognitive impairment had increased risk of death within the
      hospital (hazard ratio (HR)=3.99; 95% confidence interval (CI) 0.42-37.90;
      p=0.229), in the first year after hospitalization (HR=2.35; 95% CI 1.15-4.78;
      p=0.019), and cumulatively (HR=2.46; 95% CI 1.26-4.82; p=0.009). In this matched
      cohort of hospitalized patients > or =85 years old, cognitive impairment was
      associated with an increased mortality rate. Because of this additional risk of
      death, hospitalized geriatric patients who are cognitively impaired may merit
      closer monitoring.

PMID- 17498823
TI  - Factitious tricuspid bio-prosthesis stenosis: an unusual presentation of a left
      to-right shunt.

PMID- 17498824
TI  - Cardiac effects of L-thyroxine administration in borderline hypothyroidism.
AB  - OBJECTIVE: To investigate the clinical relevance of l-thyroxine (l-T(4))
      substitution therapy in borderline hypothyroidism. DESIGN: To assess whether and
      to what extent administration of l-T(4) is able to modify systolic and diastolic
      function in patients with subclinical hypothyroidism and in subjects with
      autoimmune thyroiditis and normal serum TSH. METHODS: We studied 26 patients with
      classical Hashimoto's thyroiditis [18 with increased serum TSH (>3 mU/ml - Group
      A), and 8 with normal serum TSH (<3 mU/ml) - Group B]; a third group (C) included
      13 healthy controls. All subjects underwent Pulsed Wave Tissue Doppler Imaging
      (PWTDI) to accurately quantify the global and regional left ventricular function.
      RESULTS: In both groups A and B we confirmed a significant impairment of systolic
      ejection (p<0.001 and p<0.05, respectively), a delay in diastolic relaxation
      (p<0.001 and p<0.05, respectively) and a decrease in the compliance to the
      ventricular filling (p<0.05). Administration of 50 microg/day of l-T(4) produced
      a progressive reduction of serum TSH (within the normal range) and normalization
      of all PWTDI parameters, which began after 6 months and finished after 12 months.
      CONCLUSION: Our data confirm previous evidence that subclinical hypothyroidism is
      associated with a cardiac dysfunction, even when this is very mild (i.e. with
      serum TSH still comprised in the normal range), and show that these abnormalities
      are reversible with l-T(4) replacement therapy.

PMID- 17498825
TI  - Relationship between QRS duration and prognosis in non-ST-segment elevation acute
      coronary syndrome.
AB  - BACKGROUND: Previous studies have shown that prolonged QRS duration increases the
      risk of death in patients with heart failure and after an ST-segment elevation
      acute myocardial infarction. Very little data exist about the prognostic
      implications of QRS duration in the non-ST-segment elevation acute coronary
      syndrome (NST-ACS): unstable angina and non-ST elevation acute myocardial
      infarction (non-STEMI). METHODS: This is a prospective and observational study in
      which we included 502 patients (age 71+/-10 years, 68% males, 29% diabetes)
      consecutively admitted for NST-ACS. QRS duration was manually measured from the
      12-lead electrocardiogram. Our aim is to assess the relation between the QRS
      duration on admission (QRSd) and the risk of cardiovascular death (CvD) in the
      long-term. RESULTS: Mean QRSd was: 93+/-19 ms. After a median follow-up of 450
      days, the cumulative incidence of CvD was: 17.8%. QRSd correlated with the
      incidence of CvD during the follow-up period: c=0.72 (p<0.001). The best cut-off
      point was 90 ms (sensitivity, specificity and negative predictive value of
      QRSd>or=90 ms for CvD: 82, 68 and 93%). According to the Kaplan-Meier analysis,
      QRSd>or=90 ms was associated with an increase in the risk of CvD: 26.6% versus
      7.2% (log rank: 28.6; p<0.001). Cumulative incidence of CvD was higher in
      QRSd>or=90 ms in patients with unstable angina: 15.5% versus 4% (p=0.02), and in
      those with non-STEMI: 30.5% versus 8.9% (p<0.001). After adjusting for other
      significant variables (Cox-regression analysis), QRSd>or=90 ms persisted as an
      independent predictor for overall CvD (Hazard Ratio: 2.62; 95% Confidence
      Interval: 1.44-4.74; p<0.001). CONCLUSION: In NST-ACS, the QRSd, even in the
      normal range, has prognostic implications. QRSd>or=90 ms is independently
      associated with an increased risk of CvD in the long-term.

PMID- 17498826
TI  - Factors influencing the prevalence of Salmonella spp. in swine farms: a meta
      analysis approach.
AB  - A systematic review and meta-analysis was conducted to identify study-level
      variables that could explain the variation in apparent Salmonella spp. prevalence
      estimates. Electronic and non-electronic literature searches from 1990 until 2005
      were carried out to identify all studies related to the prevalence of subclinical
      Salmonella infection in swine. The searches were restricted to studies published
      in English, Spanish, and French. Clinical trials or any other study where an
      intervention was evaluated were excluded from this analysis. A template was
      designed to retrieve the most relevant variables and data abstraction was
      performed in duplicate. A total of 98 papers containing 82 animal-level and 156
      farm-level studies were used in the analyses. The median farm-level and animal
      level prevalences were 59% and 17%, respectively. Meta-regression analyses were
      carried out on both farm and animal-level data. Diagnostic procedure, sample
      size, and country where study was conducted were the three most important
      predictors in explaining the differences in Salmonella prevalences between
      studies. When compared to a farm with a apparent prevalence of 50% determined by
      the blood ELISA, prevalences based on culture of fecal samples were 39% lower and
      prevalences based on cecum and tissue cultures were 16% and 19% lower,
      respectively. Similar to farm-level models, animal-level models did not show any
      difference among serological tests and prevalence values based culture procedures
      were, on average, 9% lower than those from serological tests. Sample size was
      negatively associated with prevalence estimates. In conclusion, the methodology
      was useful for identifying and quantifying sources of variation in Salmonella
      apparent prevalence among studies and for establishing prevalence distributions
      that could be used as input parameters in risk assessment and decision models.
      The analysis provides some guidelines when interpreting and comparing apparent
      Salmonella prevalence results from studies using different study designs.

PMID- 17498827
TI  - A qualitative assessment tool for the potential of infectious disease emergence
      and spread.
AB  - Improved understanding and assessment of the complex factors associated with
      disease emergence and spread will lead to better management and thus reduction of
      risk for disease occurrence. Specific biological, ecologic, environmental, and
      societal factors have been identified that precede emerging infections. Based on
      these factors, a qualitative tool was developed to assess risk for disease
      emergence and spread. Within this tool, three separate assessment elements were
      developed: novel disease evolution, pathways by which a disease agent could be
      introduced into a country, and domestic spread from the location of introduction
      or evolution. Risk factors identified for each of the three elements consist of
      specific descriptions of production practices, consumer demand, trade, health
      conditions, and environmental conditions, and are categorized as primary or
      secondary. Using this tool, those factors contributing greatest to risk of
      disease emergence can be identified and targeted for mitigation. In addition,
      risk can be monitored over time, focusing on factors that are primary or that
      have the greatest potential for increasing disease emergence risk.

PMID- 17498828
TI  - Does treating maternal depression improve child health management? The case of
      pediatric asthma.
AB  - Past studies have demonstrated an association between maternal depression and
      poor management of pediatric asthma. Using an instrumental variables strategy to
      address the endogeneity of depression treatment, I build on this literature to
      answer the question of whether treating maternal depression leads to an
      improvement in pediatric asthma management. I show that treatment of mother's
      depression improves management of child's asthma, resulting in a reduction in
      asthma costs in the 6-month period following diagnosis of $798 per asthmatic
      child whose mother is treated for depression.

PMID- 17498829
TI  - The effectiveness of cigarette regulations in reducing cases of Sudden Infant
      Death Syndrome.
AB  - Sudden Infant Death Syndrome (SIDS) is a leading cause of mortality among infants
      and is responsible for thousands of infant deaths every year. Prenatal smoking
      and postnatal environmental smoke have been identified as strong risk factors for
      SIDS. Given the link between smoking and SIDS, this paper examines the direct
      effects of cigarette prices, taxes and clean indoor air laws in explaining
      changes in the incidence of SIDS over time in the United States. State-level
      counts of SIDS cases are generated from death certificates for 1973-2003. After
      controlling for some observed and unobserved confounding factors, the results
      show that higher cigarette prices and taxes are associated with reductions in
      SIDS cases. Stronger restrictions on smoking in workplaces, restaurants and child
      care centers are also effective in reducing SIDS deaths.

PMID- 17498830
TI  - A novel target-specific gene delivery system combining baculovirus and sequence
      specific long interspersed nuclear elements.
AB  - Transposable elements are valuable for somatic and germ-line transformation.
      However, long interspersed nuclear elements (LINEs) have not been used because of
      poor information on the transposition mechanism. We have developed a novel gene
      delivery system combining baculovirus AcNPV and two silkworm LINEs, SART1 and R1,
      which integrate into specific sequences of telomeric repeats and 28S ribosomal
      DNA, respectively. When two LINEs containing the enhanced green fluorescent
      protein gene recombined into AcNPV were infected into fifth instar larvae of the
      silkworm, we observed target-specific retrotransposition of LINEs at 72h post
      infection, using polymerase chain reaction amplification and sequencing. Telomere
      and 28S rDNA-specific transposition occurred in all nine tissues tested,
      including the ovary and testis. This is the first demonstration of site-specific
      gene delivery in living larvae. Insertion efficiencies were dependent on the
      virus titer for injection and the host strains of Bombyx mori. Using this system,
      we successfully detected the intergeneration transmission of retrotransposed
      sequences. In addition, AcNPV-mediated SART1 also transposed into telomere of
      another lepidopteran, Orgyia recens, suggesting that this system is useful for a
      wide variety of AcNPV-infectious insects. Site-specific gene delivery by virus
      mediated LINE will be a potential gene therapy tool to avoid harmful unexpected
      insertions.

PMID- 17498832
TI  - Is there predictive criteria for transfer of patients to a rehabilitation ward
      after hip and knee total arthroplasty? Elaboration of French clinical practice
      guidelines.
AB  - OBJECTIVE: To develop clinical practice guidelines concerning predictive criteria
      for transfer of patients to a rehabilitation ward after hip and knee total
      arthroplasty. METHOD: The SOFMER (French Physical Medicine and Rehabilitation
      Society) methodology, associating a systematic literature review, collection of
      everyday clinical practice, and external review by a multidisciplinary expert
      panel, was used. RESULTS: From systematic literature review and collection of
      French professional practice, we cannot distinguish the patients undergoing THA
      and TKA who can transfer to a rehabilitation ward. For both types of patients,
      the main criteria determining transfer are demographic criteria such as older age
      or female sex; psychosocial and environmental criteria such as living alone,
      feeling unable to return home directly (pre-operative education could modify this
      criterion); and surgeon advice based on the pre and post-operative clinical and
      functional status. CONCLUSION: Studies with good methodological quality are
      urgently needed to evaluate the use of predictive tools such as the RAPT,
      separating THA and TKA, and using as parameters of assessment functional status
      and handicap reduction.

PMID- 17498833
TI  - Non-traditional cardiovascular risk factors contribute to peripheral arterial
      disease in patients with type 2 diabetes.
AB  - OBJECTIVE: This study evaluated the prevalence of peripheral arterial disease
      (PAD) in type 2 diabetes and its association with traditional and non-traditional
      cardiovascular (CV) risk factors. SUBJECTS AND METHODS: In 1610 type 2 diabetics
      PAD was defined as ankle-brachial pressure index (ABPI)<0.9. RESULTS: PAD
      prevalence was 17%, increased with age, diabetes duration, HbA 1c levels,
      previous CV events. There were no significant differences in the prevalence of
      traditional CV risk factors between patients with and without PAD. PAD patients
      had higher levels of fibrinogen (10.88+/-2.32 versus 10.2+/-2.23micromol/L;
      p<0.0001), uric acid (327.1+/-89.2 versus 315.2+/-83.3micromol/L, p<0.01), pulse
      pressure (70+/-18 versus 60+/-16mm Hg, p<0.0001), higher rate of microalbuminuria
      (21.3% versus 13.7%; p<0.05) and lower glomerular filtration rate (GFR, 80.7+/-24
      versus 89.9+/-22 ml/min/1.73 m2; p<0.001) than those without. In age-gender
      adjusted analysis, smoking (OR 1.5; CI: 1.07-2.2), HbA 1c (OR 1.45; CI: 1.07
      2.08), high pulse pressure (OR 2.81; CI: 1.63-4.82), reduced GFR (OR 2.16; CI:
      1.4-3.3), microalbuminuria (OR 1.62; CI: 1.11-2.36), high fibrinogen levels (OR
      2.03; CI: 1.34-3.07) were associated with PAD. In multivariate analysis age, male
      sex, smoking, high pulse pressure, low GFR, high fibrinogen levels, previous CV
      events were independent risk factors for PAD. CONCLUSIONS: PAD prevalence is high
      in Type 2 diabetic patients. Non-traditional cardiovascular risk factors may be
      involved in the development of this complication.

PMID- 17498834
TI  - Clinical aspects of physical exercise for diabetes/metabolic syndrome.
AB  - Evidence-based medicine (EBM) has come to be regarded as essential in all fields
      of medical sciences and practical medicine. In the field of diabetes and
      exercise, among the epidemiological studies of physical exercise, recent mega
      trials such as the Diabetes Prevention Program (DPP) in the U.S. have shown that
      lifestyle intervention programs involving diet and/or exercise reduce the
      progression of impaired glucose tolerance (IGT) to type 2 diabetes. In studies
      examining the endocrinological and metabolic effects of exercise, it has been
      demonstrated that physical exercise promotes the utilization of blood glucose and
      free fatty acids in muscles and lowers blood glucose levels in well-controlled
      diabetic patients. Long-term, mild, regular jogging increases the action of
      insulin in both carbohydrate and lipid metabolism without influencing body mass
      index or maximal oxygen uptake. A significant correlation has been observed
      between delta MCR (Deltainsulin sensitivity) and the average number of steps
      performed in a day. Our recent data suggested that the improved effectiveness of
      insulin that occurs as a result of physical exercise is attributable, at least in
      part, to increases in GLUT4 protein, IRS1 and PI3-kinase protein in skeletal
      muscle. As a prescription for exercise, aerobic exercise of mild to moderate
      intensity, including walking and jogging, 10-30 min a day, 3-5 days a week, is
      recommended. Resistance training of mild intensity with the use of light
      dumbbells and stretch cords should be combined in elderly individuals who have
      decreased muscle strength. An active lifestyle is essential in the management of
      diabetes, which is one of typical lifestyle-related diseases.

PMID- 17498835
TI  - Failure to validate the Health Survey for England physical activity module in a
      cardiac population.
AB  - OBJECTIVES: The Health Survey for England physical activity module interview,
      although not validated, is used as a performance indicator to see if people are
      achieving current physical activity targets and is the primary source of
      information for physical activity related policy making. The aim of this study
      was to assess the validity of the Health Survey for England physical activity
      module as a measure of physical activity in older adults with coronary heart
      disease. METHODS: Seventy-two older adults who had experienced a cardiac event
      completed the Health Survey for England physical activity interview and wore an
      accelerometer for seven consecutive days. Physical activity classification levels
      were derived from accelerometry and from the Health Survey for England physical
      activity interview, together with the number of episodes in which participants
      were moderately active for 30 min or more. RESULTS: The Health Survey for England
      physical activity interview exhibited high sensitivity (1.0) and specificity
      (0.76) for people engaged in high levels of physical activity, moderate
      sensitivity (0.40) and specificity (0.56) for people engaged in medium levels of
      physical activity and low sensitivity (0.35) and high specificity (0.92) for
      people engaged in low levels of physical activity. Compared with the
      accelerometer, the survey misclassified 63% of participants. CONCLUSIONS: The
      Health Survey for England physical activity interview misclassified true activity
      levels in older adults with heart disease by overestimating actual activity in
      the less active participants. Similar biases on self-report physical activity
      measures have been demonstrated in the general population, suggesting that the
      Health Survey for England physical activity module interview may be providing
      inaccurate information on national activity levels.

PMID- 17498836
TI  - Sema4C participates in myogenic differentiation in vivo and in vitro through the
      p38 MAPK pathway.
AB  - Sema4C is a member of transmembrane semaphorin proteins which regulate axonal
      guidance in the developing nervous system. The expression of Sema4C was
      dramatically induced not only during differentiation of C2C12 mouse myoblasts,
      but also during injury-induced skeletal muscle regeneration. C2C12 cells stably
      or transiently expressing Sema4C both showed increased myogenic differentiation
      reflected by accelerated myotube formation and expression of muscle-specific
      proteins. Overexpression of Sema4C elicited p38 phosphorylation directly, and the
      effects of Sema4C during myogenic differentiation could be abolished by the
      p38alpha-specific inhibitor SB203580. Knockdown of Sema4C by siRNA transfection
      during C2C12 myoblasts differentiation could suppress the phosphorylation of p38
      followed by dramatically diminished myotube formation. Sema4C could activate the
      myogenin promoter during myogenic differentiation. This activation could be
      abolished by p38 inhibitor SB203580. Taken together, these observations reveal
      novel functional potentialities of Sema4C which suggest that Sema4C promotes
      terminal myogenic differentiation in a p38 MAPK-dependent manner.

PMID- 17498837
TI  - UV-induced momilactone B accumulation in rice rhizosphere.
AB  - UV-irradiation increased the concentration of momilactone B in shoots and roots
      of rice seedlings, and increasing the irradiation increased the concentration.
      The concentration in 90-min UV-irradiated shoots and roots, respectively, was
      31.8- and 3.6-fold higher than that in non-irradiated shoots and roots. After UV
      irradiation the concentration of momilactone B in rice shoots decreased. There
      was, however, an accumulation of momilactone B in the medium in which UV
      irradiated seedlings were grown. Five days after UV-irradiation, momilactone B in
      the medium was at a level 2.5 times greater than on day 0, which was 47% of
      momilactone B in the seedlings, suggesting that rice may actively secrete
      momilactone B into medium. Therefore, UV-irradiation increased not only
      production of momilactone B in rice seedlings but also secretion of momilactone B
      into rice rhizosphere. As momilactone B acts as an antimicrobial and allelopathic
      agent, secretion of momilactone B into the rhizosphere may provide a competitive
      advantage for root establishment through local suppression of soil microorganism
      and inhibition of the growth of competing plant species.

PMID- 17498838
TI  - Heat-induced accumulation of chloroplast protein synthesis elongation factor, EF
      Tu, in winter wheat.
AB  - Chloroplast protein synthesis elongation factor, EF-Tu, has been implicated in
      heat tolerance in maize (Zea mays). Chloroplast EF-Tu is highly conserved, and it
      is possible that this protein may be of importance to heat tolerance in other
      species including wheat (Triticum aestivum). In this study, we assessed heat
      tolerance and determined the relative levels of EF-Tu in mature plants (at
      flowering stage) of 12 cultivars of winter wheat experiencing a 16-d-long heat
      treatment (36/30 degrees C, day/night temperature). In addition, we also
      investigated the expression of EF-Tu in young plants experiencing a short-term
      heat shock (4h at 43 degrees C). Heat tolerance was assessed by examining the
      stability of thylakoid membranes, measuring chlorophyll content, and assessing
      plant growth traits (shoot dry mass, plant height, tiller number, and ear
      number). In mature plants, relative levels of EF-Tu were determined after 7 d of
      heat stress. High temperature-induced accumulation of EF-Tu in mature plants of
      all cultivars, and a group of cultivars that showed greater accumulation of EF-Tu
      displayed better tolerance to heat stress. Young plants of all cultivars but one
      did not show significant increases in the relative levels of EF-Tu. The results
      of the study suggest that EF-Tu protein may play a role in heat tolerance in
      winter wheat.

PMID- 17498839
TI  - Menthol: a refreshing look at this ancient compound.
AB  - Menthol is a naturally occurring cyclic terpene alcohol of plant origin, which
      has been used since antiquity for medicinal purposes. Its use in dermatology is
      ubiquitous, where it is frequently part of topical antipruritic, antiseptic,
      analgesic, and cooling formulations. Despite its widespread use, it was only
      recently that the mechanism by which menthol elicits the same cool sensation as
      low temperature was elucidated upon, with the discovery of the TRPM8 receptor.
      Although almost 5 years have passed since the discovery of this receptor, many
      dermatologists are still unaware of menthol's underlying target. The purpose of
      this review is to highlight the recent advances in the mechanism of action of
      menthol and to provide an overview of its dermatologic applications.

PMID- 17498840
TI  - Body dysmorphic disorder symptoms among patients with acne vulgaris.
AB  - BACKGROUND: Acne is one of the most common concerns of patients with body
      dysmorphic disorder (BDD), a psychiatric condition defined as a preoccupation
      with a slight or imagined defect in appearance that causes significant disruption
      in daily functioning. OBJECTIVE: We sought to screen for BDD symptoms among
      patients with acne across a spectrum of acne severity. METHODS: We used a
      validated self-report questionnaire and an objective assessment of acne severity
      by a single observer. RESULTS: Rates of BDD ranged from 14.1% using more
      stringent criteria to assess acne severity to 21.1% using less stringent
      criteria. Two-fold increased odds of having BDD was seen in patients requiring
      systemic isotretinoin therapy. LIMITATIONS: Cross-sectional study design is a
      limitation. CONCLUSION: A significant proportion of patients, regardless of their
      acne severity at the time of examination, have substantial distress and
      preoccupation related to their facial appearance.

PMID- 17498841
TI  - Adherence to topical therapy increases around the time of office visits.
AB  - BACKGROUND: The efficacy of topical medications is limited by non-adherence.
      Interventions to improve adherence to topical treatments are not well
      characterized. OBJECTIVE: To assess the impact of office visits on patients'
      adherence to topical treatment. METHODS: Twenty-nine subjects enrolled in a
      clinical trial for psoriasis and were followed for up to 8 weeks. Subjects were
      told to apply 6% salicylic acid gel twice daily. Electronic monitors were used to
      assess adherence. Results were compared to adherence in clinical trials of hand
      dermatitis and atopic dermatitis. RESULTS: Adherence rates were significantly
      higher around the time of office visits (P < .05). LIMITATIONS: This is a small
      study in a limited patient population. The study was observational and not a
      randomized trial of the effect of increased office visits. CONCLUSION: Frequent
      follow-up visits in clinical trials increase patients' adherence to medications.
      The use of a follow-up visit shortly after initiating treatment may be an
      effective way to boost patients' use of their medication and achieve better
      treatment outcomes.

PMID- 17498842
TI  - Type A behaviour and consumption of an atherogenic diet: no association in the
      PRIME study.
AB  - It has previously been suggested that the association between Type A behaviour
      and coronary heart disease (CHD) may be mediated through diet. This analysis
      investigates associations between Type A behaviour and diet, with particular
      focus on foods high in saturated fats and cholesterol (cake, cheese, eggs and
      fried potatoes), foods high in unsaturated fats (fish and nuts), and fruit and
      vegetables. The analysis was conducted on data collected from 10,602 men from
      Northern Ireland and France screened for inclusion in the PRIME cohort study.
      Type A behaviour was measured using the Framingham Type A Behaviour Patterns
      Questionnaire, diet was measured using a Food Frequency Questionnaire and various
      demographic details were also assessed. Levels of Type A behaviour and intakes of
      all food groups were similar to previous studies. Using regression, Type A
      behaviour was significantly associated with diet, and specifically with a higher
      consumption of cheese and vegetables in Northern Ireland, and a higher
      consumption of cake, fish and vegetables in France. These associations are most
      plausibly explained as a result of lifestyle, although the possibility of
      independent associations between Type A behaviour and diet remains. The work is
      limited by the use of questionnaires, but the findings available suggest that
      Type A behaviour is unlikely to be associated with the consumption of a diet that
      has previously been linked to CHD. These findings suggest that any association
      between Type A behaviour and CHD is unlikely to be mediated through diet.

PMID- 17498843
TI  - Resistance to disinfectants in epidemiologically defined clinical isolates of
      Acinetobacter baumannii.
AB  - Decreased susceptibility to biocides may contribute to epidemic spread of
      Acinetobacter baumannii in the hospital. This study was conducted to evaluate the
      susceptibility of different clinical A. baumannii strains to disinfectants.
      Twenty A. baumannii strains were examined, ten of which were outbreak-related and
      ten that were sporadic. Clinical isolates were selected on the basis of
      demonstrating a unique pulsed-field gel electrophoresis pattern. The in-vitro
      activities of propanol, combination of 1-propanol, 2-propanol and mecetronium
      ethylsulphate, polyvinylpyrrolidone (PVP)-iodine, triclosan and chlorhexidine
      were determined using a broth macrodilution method. Exposure times to the
      disinfectant ranged from 15 s to 2 min and concentrations ranged from undiluted
      to a 1:4000 dilution in order to investigate the impact of inadvertent dilution
      that might occur in clinical practice. Five American Type Culture Collection
      (ATCC) type strains (A. baumannii, Escherichia coli, Pseudomonas aeruginosa,
      Enterococcus faecalis and Staphylococcus aureus) were used as controls. All
      disinfectants inhibited growth of all isolates at concentrations and contact
      times recommended by the respective manufacturer. With most of the disinfectants
      tested, a relevant number of viable bacteria remained if contact times < 30s or
      diluted agents were used. No significant differences in susceptibility between
      outbreak-related and sporadic strains were detected, but larger studies would be
      required to confirm this. Resistance to currently used disinfectants is probably
      not a major factor in the epidemic spread of A. baumannii. However, even minor
      deviations from the recommended procedures leading to decreased concentrations or
      exposure times may play a role in nosocomial cross-transmission.

PMID- 17498844
TI  - A clinical decision rule to identify which chest pain patients can safely be
      removed from cardiac monitoring in the emergency department.
AB  - STUDY OBJECTIVE: We determine the rate of serious arrhythmias in a cohort of
      monitored emergency department (ED) chest pain patients and derive a clinical
      decision rule that can identify which patients can safely be taken off continuous
      cardiac monitoring at initial physician assessment. METHODS: A secondary analysis
      of a prospectively collected cohort was completed in a university-affiliated
      tertiary care center. Consecutive patients with a primary complaint of chest pain
      who underwent cardiac monitoring in the ED in January to April 2000 were
      included. Serious arrhythmias were defined as those requiring treatment in the
      ED. Multivariate recursive partitioning analysis was undertaken to derive a
      decision rule. RESULTS: Nine hundred ninety-two consecutive chest pain patients
      were monitored in the ED during the study period, of whom 14% and 12% had
      myocardial infarction and unstable angina, respectively. There were 17 patients
      (1.7%) with serious arrhythmias detected in the ED. The following decision rule
      was derived: patients can be removed from cardiac monitoring if they are pain
      free at the initial physician assessment and have a normal or nonspecific ECG
      result. The rule had 100% sensitivity (95% confidence interval 80% to 100%) for
      serious arrhythmias. Applying this rule would have allowed physicians to
      immediately remove 29% of patients from cardiac monitoring. CONCLUSION: Serious
      arrhythmias are uncommon in monitored ED chest pain patients. A simple clinical
      decision rule could be used to safely identify low-risk patients who can be
      removed from continuous monitoring if its performance is prospectively validated
      in an independent patient population.

PMID- 17498845
TI  - What whiteboards in a trauma center operating suite can teach us about emergency
      department communication.
AB  - STUDY OBJECTIVE: Highly reliable, efficient collaborative work relies on
      excellent communication. We seek to understand how a traditional whiteboard is
      used as a versatile information artifact to support communication in rapid-paced,
      highly dynamic collaborative work. The similar communicative demands of the
      trauma operating suite and an emergency department (ED) make the findings
      applicable to both settings. METHODS: We took photographs and observed staff's
      interaction with a whiteboard in a 6-bed surgical suite dedicated to trauma
      service. We analyzed the integral role of artifacts in cognitive activities as
      when workers configure and manage visual spaces to simplify their cognitive
      tasks. We further identified characteristics of the whiteboard as a communicative
      information artifact in supporting coordination in fast-paced environments.
      RESULTS: We identified 8 ways in which the whiteboard was used by physicians,
      nurses, and with other personnel to support collaborative work: task management,
      team attention management, task status tracking, task articulation, resource
      planning and tracking, synchronous and asynchronous communication,
      multidisciplinary problem solving and negotiation, and socialization and team
      building. The whiteboard was highly communicative because of its location and
      installation method, high interactivity and usability, high expressiveness, and
      ability to visualize transition points to support work handoffs. CONCLUSION:
      Traditional information artifacts such as whiteboards play significant roles in
      supporting collaborative work. How these artifacts are used provides insights
      into complicated information needs of teamwork in highly dynamic, high-risk
      settings such as an ED.

PMID- 17498846
TI  - The need for emergency medicine resident training in forensic medicine.

PMID- 17498847
TI  - Usability study of two common defibrillators reveals hazards.
AB  - STUDY OBJECTIVE: This usability study evaluates the user interface of 2 common
      monitor-defibrillators, the Lifepak10 and Lifepak12, to identify use-related
      hazards. METHODS: Fourteen paramedics familiar with both devices completed 4 EMS
      simulator scenarios using each device. The scenarios involved "quick look" and
      monitoring, defibrillation, synchronized cardioversion, and replacing paper.
      Qualitative and quantitative data were collected, including both participant self
      evaluation (scored 1 to 9) and expert observer evaluation (scored 0 to 4).
      RESULTS: Participant ratings demonstrated that for performing a quick look, the
      Lifepak10 was easier to use (mean 8.0 versus 7.1), and for synchronized
      cardioversion the Lifepak12 was easier (mean 6.7 versus 5.3). Participants
      performed better on the Lifepak12 than the Lifepak10 for synchronized
      cardioversion (mean 3.1 versus 1.6) and replacing paper (mean 3.0 versus 2.1).
      One participant did not complete the final questionnaire. Of the remaining 13, 11
      (85%) participants preferred the Lifepak12 for use on a regular basis. Eight
      (62%) paramedics thought that the Lifepak12 would be more effective in an
      emergency; 9 (69%) believed that the Lifepak10 is quicker to learn. Paramedics
      reported difficulty using the devices with gloves and confusion in "sync" mode.
      Of note, 50% of participants inadvertently delivered an unsynchronized
      countershock for supraventricular tachycardia. CONCLUSION: Although the Lifepak10
      is easier to learn, the Lifepak12 is perceived as easier to use and more
      effective in emergencies. The high failure rate in synchronized cardioversion
      indicates a need to reevaluate the user interface design for this function.
      Limitations of this study include the use of simulation.

PMID- 17498848
TI  - Synthesis, characterization, cytotoxicity, antibacterial and antifungal
      evaluation of some new platinum (IV) and palladium (II) complexes of
      thiodiamines.
AB  - Some new platinum (IV) and palladium (II) thiodiamine complexes of type
      [Pt(L)2Cl2] and [Pd(L)Cl2], [where, L=(cyclohexyl-N-thio)-1,2-ethylenediamine
      (L(1)) and (cyclohexyl-N-thio)-1,3-propanediamine (L(2))] have been synthesized.
      The thiodiamines coordinate as a bidentate N-S ligand. The synthesized platinum
      (IV) and palladium (II) complexes of the thiodiamines were characterized by
      elemental analysis, IR, mass, electronic and (1)H NMR spectroscopic studies.
      These complexes were also screened for cytotoxicity, in vitro antifungal and in
      vitro antibacterial activities. Thermodynamic parameters such as activation
      energy (Ea), apparent activation entropy (S(#)) and enthalpy change (DeltaH) for
      the dehydration and decomposition reactions of one complex has also been
      evaluated.

PMID- 17498849
TI  - N-[2-(5,5-dimethyl-1,3-dioxane-2-yl)ethyl]amino acids: their synthesis, anti
      inflammatory evaluation and QSAR analysis.
AB  - Developing novel anti-inflammatory drugs is increasingly important in modern
      pharmaceutical industry. In this work, the reactions of both amino acids and
      their methylesters with 3-(5,5-dimethyl-1,3-dioxane-2-yl)propanal (2) were
      performed to either directly provide the goal products N-[2-(5,5-dimethyl-1,3
      dioxane-2-yl)ethyl]amino acids (4a-s) in 9-65% yields or provide the
      intermediates N-[2-(5,5-dimethyl-1,3-dioxane-2-yl)ethyl]amino acid methylesters
      (3a-s) in 78-87% yields. The saponification of 3a-s provided 4a-s in 80-89%
      yields. Using a xylene-induced ear edema model, the anti-inflammatory activities
      of these newly synthesized anti-inflammatory agents were evaluated. The results
      indicated that comparing to the vehicle control 17 out of 4a-s significantly
      inhibited the development of inflammation in mice (p<0.01). In particular, eight
      out of 4a-s exhibited an even higher anti-inflammatory activity than the standard
      reference drug aspirin (p<0.05-0.01). A QSAR analysis was performed by use of the
      molecular descriptors generated from e-dragon software. The predictive accuracy
      of the established QSAR model implies that it may be promising for screening the
      new derivatives of 2-position amino acid substituted 1,3-dioxanes as potential
      anti-inflammatory agents.

PMID- 17498850
TI  - Effects of protein-rich supplementation and nandrolone on bone tissue after a hip
      fracture.
AB  - BACKGROUND & AIMS: Osteoporosis is a major health problem worldwide. Low weight
      is a major risk factor for low bone mass and fractures. The aim of this study was
      to investigate the effects on bone tissue of protein-rich supplementation alone
      or in combination with nandrolone decanoate in lean elderly women after a hip
      fracture. METHODS: Sixty elderly women with BMI <24 kg/m(2) admitted to hospital
      due to a femoral neck fracture were randomised to a control group, to receive a
      protein-rich formula or to receive the same formula with an addition of
      nandrolone decanoate for 6 months. All patients received additional calcium and
      vitamin D. The effects after 6 and 12 months were measured by means of bone
      mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), and with
      biochemical bone markers. Osteocalcin and C-terminal telopeptide of collagen-1
      (CTX) were used to estimate bone formation and bone resorption, respectively.
      RESULTS: The analyses showed an increase in total body BMD at 6 and 12 months in
      patients who received protein-rich supplementation. Nandrolone decanoate did not
      appear to have any additional effect on BMD. Osteocalcin increased in all groups
      while no significant changes were found for CTX. CONCLUSION: The overall results
      of the study indicated that protein-rich supplementation given to lean elderly
      female hip fracture patients increased the total body BMD.

PMID- 17498851
TI  - A new vaccine adjuvant (BOS 2000) a potent enhancer mixed Th1/Th2 immune
      responses in mice immunized with HBsAg.
AB  - Adjuvants in vaccines are immune stimulants that play an important role in the
      induction of effective and appropriate immune responses to vaccine component. In
      search of a potent vaccine adjuvant, the water-soluble biopolymeric fraction BOS
      2000 from Boswellia serrata was evaluated for desired activity. We investigated
      the ability of BOS 2000 to enhance HBsAg specific immune responses. The effect
      was determined in the form of protective anti-HBsAg titers, neutralizing
      antibodies (IgG1 and IgG2a), spleen cell lymphocyte proliferation by using MTT
      assay, Th1 (IFN-gamma and TNF-alpha) and Th2 (IL-4) cytokines as well as T
      lymphocyte subsets (CD4/CD8) and intracellular cytokines (IFN-gamma/IL-4), these
      responses were highest in BOS 2000 immunized mice. Alum induced only a modest
      enhancement of antibody responses. Reducing the dose of adjuvant by 18.1-fold in
      comparison to alum, total IgG and its subtypes (IgG1 and IgG2a) antibodies titer
      in serum was significantly enhanced. Analysis of HBsAg specific cytokines
      revealed that alum was associated with a predominantly IL-4 response. In
      contrast, BOS 2000 was associated with production of both IFN-gamma and IL-4. We
      conclude that BOS 2000 is a potent enhancer of antigen-specific Th1 and Th2
      immune responses in comparison to alum with Th2 limitation and is a promising
      adjuvant for vaccine applications.

PMID- 17498852
TI  - A new attenuated Mycobacterium bovis vaccine protects brushtail possums
      (Trichosurus vulpecula) against experimental tuberculosis infection.
AB  - Vaccination of wildlife against bovine tuberculosis is being actively considered
      in countries that have wildlife reservoirs of Mycobacterium bovis infection. A
      newly attenuated strain of M. bovis (WAg533) was produced as part of a programme
      to develop a better vaccine than BCG to control tuberculosis in brushtail possums
      in New Zealand. The vaccine efficacy of WAg533 in possums was compared to BCG
      using three different methods of inoculation (conjunctival/intranasal, oral and
      sub-cutaneous) followed by aerosol challenge. Overall, WAg533 was a more potent
      vaccine than BCG and by two methods of inoculation gave more measures of
      protection that were significantly different from controls.

PMID- 17498853
TI  - Investigation of mumps vaccine failures in Minsk, Belarus, 2001-2003.
AB  - The purpose of this study was to investigate mumps vaccine failures (VF) in a
      highly vaccinated population of Minsk, Belarus, and to investigate a possible
      role for virus strain-specific immunity. During our 3-year study period, 22
      adults were admitted to the Infectious Diseases Hospital in Minsk with a
      diagnosis of mumps. A genotype H1 mumps virus (MuV) strain was identified in all
      patients. Of 15 patients from whom the paired sera were collected, 9 were
      confirmed to have been previously vaccinated. Serological examinations indicated
      primary VF in seven of these cases and secondary VF in two. Despite almost all
      vaccinated patients possessing MuV specific IgG, few possessed neutralizing
      antibody to the vaccine strain and titers were nominal. Importantly, none of the
      sera were able to neutralize a genotype H MuV strain. Our results demonstrate the
      importance of assaying for neutralizing antibody and support the assertion that
      antigenic differences between wild type and vaccine MuV strains may play a role
      in cases of breakthrough infection in vaccinees.

PMID- 17498854
TI  - Evaluation of different promoter sequences and antigen sorting signals on the
      immunogenicity of Bacillus subtilis vaccine vehicles.
AB  - Recombinant Bacillus subtilis strains, either in the form of spores or vegetative
      cells, may be employed as safe and low-cost vaccine vehicles. In this study, we
      studied the role of promoter sequences and antigen-sorting signals on the
      immunogenicity based on previously constructed B. subtilis episomal expression
      systems. Mice orally immunized with spores or cells encoding the B subunit of the
      heat labile toxin (LTB), originally expressed by some enterotoxigenic Escherichia
      coli (ETEC) strains, under control of the stress-inducible gsiB promoter
      developed higher anti-LTB serum IgG and fecal IgA responses with regard to
      vaccine strains transformed with plasmids encoding the antigen under control of
      IPTG-inducible (Pspac) or constitutive (PlepA) promoters. Moreover, surface
      expression of the vaccine antigen under the control of the PgsiB promoter
      enhanced the immunogenicity of vegetative cells, while intracellular accumulation
      of LTB led to higher antibody responses in mice orally immunized with recombinant
      B. subtilis spores. Specific anti-LTB antibodies raised in vaccinated mice
      recognized and neutralized in vitro the native toxin produced by ETEC strains.
      Nonetheless, only mice orally immunized with recombinant B. subtilis strains,
      either as vegetative cells or spores, expressing intracellular LTB under the
      control of the gsiB promoter conferred partial protection to lethal challenges
      with purified LT. The present report further demonstrates that B. subtilis
      plasmid-based heterologous protein expression systems are adequate for antigen
      delivery via the oral route.

PMID- 17498855
TI  - Influenza vaccination for severely multiply handicapped persons/children in the
      2005-2006 season.
AB  - In this study, we report the effectiveness of trivalent inactivated influenza
      vaccination (TIV) for severely multiply handicapped persons/children (SMHPs) in
      the 2005-2006 season. In 77 SMHPs, A/New York/55/2004 (H3N2) which was the
      changed vaccine-strain showed significant differences in the geometric mean
      titers (P<0.05) and seroprotection rates (P<0.01) between pre- and post
      vaccination. A/New Caledonia/20/99 (H1N1) and B/Shanghai/361/2002, which were the
      unchanged vaccine-strains, showed no significant differences. We defined the
      potential responders as those who can achieve 1:40 or more hemagglutination
      inhibition (HAI) titer after vaccination with any vaccine-strain. Therefore, the
      rate of potential responders is equivalent to the rate of seroprotection,
      estimated to be 40-60% among the SMHPs and >80% among the control group in this
      study. In the SMHPs, even potential responders could only achieve limited HAI
      titers (1:40-80) even after repeated vaccination. In contrast, the control group
      showed higher HAI titers compared to the SMHPs for the unchanged vaccine-strains
      caused by the priming effect. These data suggest that it might be difficult for
      SMHPs (including potential responders) to achieve the priming effect by the
      current TIV. Consequently, they cannot obtain a booster effect.

PMID- 17498856
TI  - Mumps outbreak in a highly vaccinated school population: assessment of secondary
      vaccine failure using IgG avidity measurements.
AB  - From March to April 2006, an outbreak of mumps occurred in Gyeonggi, Korea. The
      aim of this study was to describe and discriminate between primary and secondary
      vaccine failure in a highly vaccinated population for mumps using IgG avidity
      testing. Fifteen clinical mumps cases occurred among 41 students. Among these 15
      patients, 11 vaccinated patients were considered secondary vaccine failures with
      high IgG titers and a high avidity index (AI, > or =32%); an unvaccinated patient
      was considered to have primary infection with high IgG titers and low AI, and
      three vaccinated patients were considered as other infections with low IgG titers
      and low AI. Among 26 unaffected students, 5 vaccinated patients were
      retrospectively diagnosed as sub-clinical infection with high IgG titers and high
      AI; the remaining students had low IgG titers and low AI except for one
      previously infected student. The results of this study show that secondary
      vaccine failure played an important role in this mumps outbreak. Therefore,
      booster immunization for mumps should be considered in immunized adolescents to
      prevent further outbreaks.

PMID- 17498857
TI  - Oral administration of BCG encapsulated in alginate microspheres induces strong
      Th1 response in BALB/c mice.
AB  - Bacille Calmette-Guerin (BCG) is one of the first vaccines administered to the
      newborns in developing countries. As an alternative to parenteral administration
      of vaccines, oral vaccines offer significant logistical advantages. Successful
      oral immunization, however, requires that vaccine antigens be protected from
      gastric secretions. In the present study, BALB/c mice were vaccinated orally with
      BCG encapsulated in alginate microspheres and the immune responses and protective
      effect were compared with those of mice vaccinated with free BCG by subcutaneous
      and oral routes. Proliferative and delayed-type hypersensitivity (DTH) responses
      and IFN-gamma production were significantly higher in mice immunized orally with
      encapsulated BCG in comparison with results of mice immunized orally with free
      BCG. Following systemic infection with BCG, mice vaccinated with encapsulated BCG
      had lower mean bacterial count compared to those vaccinated orally with free BCG.
      The immune responses induced by oral administration of encapsulated BCG were
      equal to or better than the responses induced by standard BCG vaccination.

PMID- 17498859
TI  - Possible involvement of oxidative stress in piperonyl butoxide induced
      hepatocarcinogenesis in rats.
AB  - To clarify the possible mechanism of non-genotoxic hepatocarcinogenesis induced
      by piperonyl butoxide (PBO), male F344 rats were administered an i.p. injection
      of N-diethylnitrosamine (DEN) to initiate hepatocarcinogenesis. Two weeks later,
      the rats were administered a PBO-containing (0, 1, or 2%) diet for 6 weeks and
      subjected to a two-third partial hepatectomy 1 week later. After sacrificing them
      on week 8, their livers were histopathologically examined and analyzed for gene
      expression using a microarray and real-time RT-PCR. Reactive oxygen species (ROS)
      products were also measured using liver microsomes. Hepatocytes exhibited
      centrilobular hypertrophy and increased glutathione S-transferase placental form
      (GST-P) positive foci formation. ROS products increased significantly in liver
      microsomes. In the microarray analysis, the expressions of genes related to
      metabolism and oxidative stress - NAD(P)H dehydrogenase, quinone 1 (Nqo1), UDP
      glucuronosyltransferase (UDPGTR-2), glutathione peroxidase 2 (Gpx2), glutathione
      reductase (GRx) - multidrug resistance associated protein 3 (Abcc3), and solute
      carrier family 7 (cationic amino acid transporter, y+ system) member 5 (Slc7a5)
      were up-regulated in the PBO group in comparison to the 0% PBO group; this was
      confirmed by real-time RT-PCR. Additionally, a significant up-regulation of
      stress response related genes such as CYP1A1 was observed in PBO-treated groups
      in real-time RT-PCR. HPLC analysis revealed that the level of 8-OHdG in the 2%
      PBO group was significantly higher than that in the 0% PBO group. This suggests
      that PBO has the potential to generate ROS via metabolic pathways and induce
      oxidative stress, including oxidative DNA damage, resulting in the induction of
      hepatocellular tumors in rats.

PMID- 17498860
TI  - The interaction of chromium (VI) with macrophages: depletion of glutathione and
      inhibition of glutathione reductase.
AB  - There are reports of alterations in the number and functions of the cells of the
      immune system in patients with metal-on-metal (MOM) orthopaedic implants. These
      effects have been correlated with elevated chromium levels in the patients'
      blood. We have investigated the interactions of clinically relevant
      concentrations of Cr VI with macrophages in vitro, and the mechanisms responsible
      for its toxicity. Cr VI causes a concentration dependent decrease in macrophage
      viability above 1 microM as measured by the MTT and Neutral Red assays. This
      falls well within the range of circulating chromium serum concentrations measured
      in patients with MOM. Intracellular reduced glutathione (GSH) levels fall as a
      result, and most of the loss (86%) is accounted for by oxidation to the dimer,
      GSSG. Prior depletion of GSH does not sensitise the cells to Cr VI toxicity,
      implying that it is not involved in protecting the cells against the effects of
      Cr VI. During the metabolism of Cr VI, glutathione reductase activity is
      inhibited. In contrast, the activities of catalase and superoxide dismutase are
      not significantly altered. Prior inhibition of glutathione reductase activity
      protects against the toxicity of Cr VI to a significant extent, suggesting that
      it reduces Cr VI to a toxic metabolite.

PMID- 17498861
TI  - Heritability of EEG coherence in a large sib-pair population.
AB  - The additive genetic heritability of bipolar EEG coherence in a sample of 305 non
      twin sibships comprising 690 individuals (age range 7-65) was estimated.
      Heritabilities were examined in 6 frequency bands for each of 15 coherence pairs,
      both interhemispheric and intrahemispheric. The heritabilities of the bipolar EEG
      coherence ranged from 0.22 to 0.63 in 79 of the 90 phenotypes which had
      coherences high enough to provide meaningful values for the estimation of
      heritability. Heritabilities were greatest in the low and high alpha frequency
      bands, while theta and beta bands had comparable heritabilities. Coherences
      themselves were greatest in the low and high alpha frequency bands, while theta
      coherences were somewhat larger than beta. Higher heritability values were not
      associated with higher coherences. The examination of bivariate genetic
      correlations suggests that there is a difference between theta and alpha bands in
      genetic control of interhemispheric coherence.

PMID- 17498862
TI  - Identification and characterization of protein folding intermediates.
AB  - In order to understand the mechanism by which a polypeptide chain folds into its
      functionally active native state it is necessary to characterize in detail all
      the species accumulated along the pathway. The elusive nature of protein folding
      intermediates poses their identification and characterization as an extremely
      difficult task in the protein folding field. In the case of small single domain
      proteins, the direct measurement of the thermodynamics and structural parameters
      of protein folding intermediates has provided new insights on the nature of the
      forces involved in the stabilization of nascent protein structures. Here we
      summarize some of the experimental approaches aimed at the detection and
      characterization of folding intermediates along with a discussion of some general
      structural features emerging from these studies.

PMID- 17498863
TI  - Effects of nano-SiO(2) and different ash particle sizes on sludge ash-cement
      mortar.
AB  - The effects of nano-SiO(2) on three ash particle sizes in mortar were studied by
      replacing a portion of the cement with incinerated sewage sludge ash. Results
      indicate that the amount of water needed at standard consistency increased as
      more nano-SiO(2) was added. Moreover, a reduction in setting time became
      noticeable for smaller ash particle sizes. The compressive strength of the ash
      cement mortar increased as more nano-SiO(2) was added. Additionally, with 2% nano
      SiO(2) added and a cure length of 7 days, the compressive strength of the ash
      cement mortar with 1 microm ash particle size was about 1.5 times better that of
      75microm particle size. Further, nano-SiO(2) functioned to fill pores for ash
      cement mortar with different ash particle sizes. However, the effects of this
      pore-filling varied with ash particle size. Higher amounts of nano-SiO(2) better
      influenced the ash-cement mortar with larger ash particle sizes.

PMID- 17498865
TI  - Laparoscopic partial nephrectomy with clamping of the renal parenchyma: initial
      experience.
AB  - OBJECTIVES: Partial nephrectomy by laparoscopy offers patients conservative
      surgery and a mini-invasive approach; however, clamping of the renal pedicle and
      the induced warm ischaemia can damage the renal parenchyma. We present a
      technique of laparoscopic partial nephrectomy with haemostasis obtained by
      clamping of the renal parenchyma. METHODS: The procedure was performed by an
      intraperitoneal or a retroperitoneal approach. After a working space is created
      by pneumodissection, Gerota's fascia is incised and the kidney convexity is
      dissected. An endoscopic Satinsky clamp is inserted percutaneously through a 1-cm
      incision. The renal parenchyma is clamped and the tumour is excised in a
      bloodless field. The cut renal parenchyma is coated with biologic glue. RESULTS:
      Five patients with elective indications were operated. Mean age was 67.8 yr and
      mean tumour diameter 3.06 cm. One lesion was located at the upper pole and four
      at the lower pole. Mean preoperative serum creatinine level was 10.9 mg/l.
      Postoperative serum creatinine level was unchanged. Mean operative time was 238
      min. There was no conversion. Mean blood loss was 250 ml; no transfusions were
      necessary. The collecting duct system was repaired in one patient. No
      complication was noticed. Resection margins were tumour free in all cases. Final
      pathologic examination revealed clear cell carcinoma in three cases and
      angiomyolipoma and oncocytoma in one case each. CONCLUSION: Laparoscopic partial
      nephrectomy with clamping of the renal parenchyma can be performed in selected
      patients with peripherally placed tumours. The procedure avoids warm ischaemia of
      the normal parenchyma while allowing the surgeon to operate in an almost
      bloodless field. This initial experience in five patients should be validated in
      a larger series.

PMID- 17498864
TI  - Resection of abdominal solid organs using high-intensity focused ultrasound.
AB  - Our objective was to evaluate high-intensity focused ultrasound (HIFU) for
      minimizing blood loss during surgery by hemodynamically isolating large portions
      of solid organs before their resection. A high-power HIFU device (in situ
      intensity of 9000 W/cm(2), frequency of 3.3 MHz) was used to produce a wall of
      cautery for sealing of blood vessels along the resection line in surgically
      exposed solid organs (liver lobes, spleen and kidneys) of eight adult pigs.
      Following HIFU application, the distal portion of the organ was excised using a
      scalpel. If any blood vessels were still bleeding, additional HIFU application
      was used to stop the bleeding. The resection was achieved in 6.0 +/- 1.5 min
      (liver), 3.6 +/- 1.1 min (spleen) and 2.8 +/- 0.6 min (kidneys) of HIFU treatment
      time, with no occurrence of bleeding for up to 4 h (until sacrifice). The
      coagulated region at the resection line had average width of 3 cm and extended
      through the whole thickness of the organ (up to 4 cm). Blood vessels of up to 1
      cm in size were occluded. This method holds promise for future clinical
      applications in resection of solid tumors and hemorrhage control from high-grade
      organ injuries.

PMID- 17498866
TI  - Semen quality in men with malignant diseases before and after therapy and the
      role of cryopreservation.
AB  - OBJECTIVE: To review the literature and answer questions about semen quality in
      young cancer patients before and after therapy and the importance of sperm
      cryopreservation. METHODS: All aspects of sperm cryopreservation and effects of
      therapies on semen quality were examined on the basis of MedLine database
      searches. RESULTS: Chemotherapy, radiation, or their combination results in a
      significant reduction of sperm quality and as a consequence an indefinite time of
      infertility follows. The type of cancer and the pretreatment sperm concentrations
      were the most significant factors governing posttreatment semen quality and
      recovery of spermatogenesis. Due to their age, fertility and sexual functioning
      are key issues for these patients. Yet there is no medical protection of the
      germinal epithelium available. Male germ cell transplantation is in its infancy
      and still there are no therapeutical options to improve spermatogenesis after
      damage has occurred. Consequently, cryopreservation represents the only
      preemptive measure for conserving fertility. CONCLUSION: This manuscript updates
      the current knowledge of diverse chemotherapeutic treatment regimens and their
      gonadotoxic effects as well as the development of posttreatment fertility in
      cancer patients. The importance and rationale of sperm cryopreservation are
      discussed and possible future options are highlighted.

PMID- 17498867
TI  - Holmium laser enucleation of the prostate (HoLEP): long-term results, reoperation
      rate, and possible impact of the learning curve.
AB  - OBJECTIVES: To evaluate long-term outcomes and reoperation rate of holmium laser
      enucleation of the prostate (HoLEP) for patients with symptomatic enlarged
      prostate, including patients who were operated during the learning curve.
      METHODS: A retrospective analysis of 118 patients who underwent HoLEP between
      March 1998 and February 2001 at our institution. This analysis represented our
      initial experience with the technique reflecting our learning curve. The voiding
      outcome parameters, operative duration time, enucleation time, morcellation time,
      eucleated tissue weight, catheterization time, hospital stay, and complications
      were recorded. RESULTS: The mean patient age was 76.5 yr (range: 59-93) and the
      mean preoperative prostate volume was 59.3 cc (range: 20-172). The mean follow-up
      period was 49.4+/-28.1 mo. The mean catheter time and hospital stay was 1.3 and
      1.5 d, respectively. Seventy-eight percent of the patients were discharged home
      within 24h after surgery. For the patients (n=26) who had objective data at 6 yr
      postoperatively, mean maximum flow rate increased from 6.3 to 16.2ml/s and mean
      postvoid residual urine decreased from 232 to 41.2ml (p<0.0001). Mean
      International Prostate Symptom Score improved from 17.3 to 5.6 (p<0.0001).
      Bladder-neck contracture and urethral stricture developed in 0.8% and 1.7% of
      patients, respectively. The reoperation rate for recurrent benign prostatic
      hyperplasia obstruction was 4.2%. CONCLUSIONS: HoLEP represents a safe and
      effective treatment for patients with symptomatic enlarged prostate. The
      improvement in outcome parameters is durable, and the late complications and
      reoperation rate are very low.

PMID- 17498868
TI  - Editorial comment on: Holmium laser enucleation of the prostate (HoLEP): long
      term results, reoperation rate, and possible impact of the learning curve.

PMID- 17498870
TI  - Genomic instability and increased expression of BUB1B and MAD2L1 genes in ductal
      breast carcinoma.
AB  - In a series of invasive ductal breast carcinoma, we investigated the status of
      chromosomal and intrachromosomal instability by fluorescence in situ
      hybridisation and determined the level of mRNA expression for two genes involved
      in the mitotic spindle checkpoint pathway, BUB1B and MAD2L1. All breast cancers
      demonstrated higher chromosomal instability rates in tumor samples (average:
      56.86%, range: 36.24-76.78%) than in controls (average: 11.54%, range: 9.91
      14.84%) (P<0.0001). As well as intrachromosomal instability rates were elevated
      in tumor (average: 18.45% range: 8.34-35.8%) as compared with controls (average:
      4.18% range: 3.47-4.81%) (P<0.0001). An increase in BUB1B and MAD2L1 transcripts
      was demonstrated in the majority of the tumor tested. BUB1B mRNA levels but not
      MAD2L1 levels correlated with intrachromosomal instability (r=0.722, P=0.018).

PMID- 17498871
TI  - Solid-phase extraction of Fe(III), Pb(II) and Cr(III) in environmental samples on
      amberlite XAD-7 and their determinations by flame atomic absorption spectrometry.
AB  - This paper describes a simple and accurate procedure for preconcentration of
      trace amounts of Fe(III), Pb(II) and Cr(III) ions. The preconcentration procedure
      is based on retention of p-xylenol blue chelates on Amberlite XAD-7. The analytes
      retained were eluted from Amberlite XAD-7 by using 1 mol L(-1) HCl. The
      influences of the analytical parameters including amounts of reagents, pH and
      type of eluent were also investigated. The detection limits of Fe, Pb and Cr were
      found to be 3.07, 18.6 and 3.27 microg L(-1), respectively. The accuracy of the
      procedure was checked by the analysis of an electrolytic copper wire sample. The
      relative error was less than 5%. The presented method was applied to the
      determination of Fe(III), Pb(II) and Cr(III) in water samples from Denizli,
      Turkey with good results such as recoveries more than 95%, relative standard
      deviations below 10%.

PMID- 17498872
TI  - Review of procedures involving separation and preconcentration for the
      determination of cadmium using spectrometric techniques.
AB  - Spectrometric techniques for the analysis of trace cadmium have developed rapidly
      due to the increasing need for accurate measurements at extremely low levels of
      this element in diverse matrices. This review covers separation and
      preconcentration procedures, such as electrochemical deposition, precipitation,
      coprecipitation, solid phase extraction, liquid-liquid extraction (LLE) and cloud
      point extraction (CPE), and consider the features of the their application with
      several spectrometric techniques.

PMID- 17498873
TI  - Metal sorption on soils as affected by the dissolved organic matter in sewage
      sludge and the relative calculation of sewage sludge application.
AB  - To evaluate the influences of sewage sludge-derived organic matters on metal
      sorption and on the resultant sludge loading estimates, a batch experiment was
      conducted to compare the sorption of Ni, Cu and Pb in sewage sludge filtrates
      (1:20 sewage sludge to water) on eight soils and the adsorption of metals in a
      reference solution which had the same matrix as the sewage sludge filtrate except
      dissolved organic material (henceforth referred to as reference solution). Metal
      sorption could be well fitted by linear isotherm and the dissolved organic matter
      in sludge significantly depressed the sorption (p<0.01). The main factor
      controlling sorption of Ni on different soils was dominated by soil cation
      exchange capacity (CEC) and sorption of Cu and Pb was by soil organic matter
      (SOM). The parameters obtained from the sorption isotherm equations were then
      used to estimate sludge loadings into the soils. When the sorption parameters
      derived from the reference solution were used for calculation, that is the effect
      of dissolved organic matter was not considered, the calculated safe application
      rates are approximately 47.8, 51.4, 34.2, 31.3, 21.7, 46.3, 187.1 and 27.6 t
      sludge/ha for the Beijing, Jiangxi, Xiamen, Jilin, Guangdong, Wuhan, Gansu and
      Xinjiang soils, respectively. However, when the sorption parameters derived from
      the dissolved organo-metallic complexes are used for calculation, the
      corresponding application rates are reduced to approximately 6.0, 3.4, 1.9, 10.0,
      6.3, 3.6, 7.3 and 3.5 t-sludge/ha, respectively. By this study we can get a
      conclusion that the effect of sewage sludge derived dissolved organic matter on
      heavy metal sorption and soil properties should be considered in the course of
      regulating the safe application rates of sewage sludge to soil.

PMID- 17498874
TI  - Kinetic study of ozonation of molasses fermentation wastewater.
AB  - A kinetic study of molasses wastewater ozonation was carried out in a stirred
      tank reactor to obtain the rate constants for the decolorization reaction and the
      regime through which ozone is absorbed. First, fundamental mass transfer
      parameters such as ozone solubility, volumetric mass transfer coefficients and
      ozone decomposition kinetics were determined from semi-batch experiments in
      organic-free solutions with an ionic composition similar that of industrial
      wastewater. The influence of operating variables such as the stirring rate and
      gas flow rate on the kinetic and mass transfer parameters was also studied. The
      application of film theory allows to establish that the reactions between ozone
      and colored compounds in wastewater take place in the fast and pseudo-first-order
      regime, within the liquid film. The decolorization rate constants were evaluated
      at pH 8.7 and 25 degrees C, varying from 0.6 x 10(7) to 3.8 x 10(7)L mol(-1)s(
      1), depending on the stirring rate and the inlet gas flow.

PMID- 17498875
TI  - Evaluation of a risk-based environmental hot spot delineation algorithm.
AB  - Following remedial investigations of hazardous waste sites, remedial strategies
      may be developed that target the removal of "hot spots," localized areas of
      elevated contamination. For a given exposure area, a hot spot may be defined as a
      sub-area that causes risks for the whole exposure area to be unacceptable. The
      converse of this statement may also apply: when a hot spot is removed from within
      an exposure area, risks for the exposure area may drop below unacceptable
      thresholds. The latter is the motivation for a risk-based approach to hot spot
      delineation, which was evaluated using Monte Carlo simulation. Random samples
      taken from a virtual site ("true site") were used to create an interpolated site.
      The latter was gridded and concentrations from the center of each grid box were
      used to calculate 95% upper confidence limits on the mean site contaminant
      concentration and corresponding hazard quotients for a potential receptor. Grid
      cells with the highest concentrations were removed and hazard quotients were
      recalculated until the site hazard quotient dropped below the threshold of 1. The
      grid cells removed in this way define the spatial extent of the hot spot. For
      each of the 100,000 Monte Carlo iterations, the delineated hot spot was compared
      to the hot spot in the "true site." On average, the algorithm was able to
      delineate hot spots that were collocated with and equal to or greater in size
      than the "true hot spot." When delineated hot spots were mapped onto the "true
      site," setting contaminant concentrations in the mapped area to zero, the hazard
      quotients for these "remediated true sites" were on average within 5% of the
      acceptable threshold of 1.

PMID- 17498876
TI  - TBOA-sensitive uptake limits glutamate penetration into brain slices to a few
      micrometers.
AB  - Removal of neurotransmitter from the extracellular space is crucial for normal
      functioning of the central nervous system. In this study, we have used high
      affinity metabotropic glutamate receptors (mGluRs) expressed by hippocampal CA1
      pyramidal cells to test how far bath-applied glutamate penetrates into slice
      tissue before being removed by uptake mechanisms. Activation of group I mGluRs by
      100 microM DHPG produced an inward current of -48+/-10pA (I(mGluR)), which was
      blocked by application of group I mGluR antagonists. In contrast, bath
      application of 100 microM glutamate in the presence of a ionotropic glutamate
      receptor antagonist and TTX did not activate I(mGluR) in CA1 cells patch-clamped
      at a depth of approximately 30 microm. Similarly, sole inhibition of glutamate
      transporters by the broad-spectrum glutamate transporter antagonist TBOA did not
      induce I(mGluR) under the same conditions. Only if glutamate was co-applied with
      TBOA an I(mGluR) of -39+/-8pA was recorded which was also blocked by group I
      antagonists. The data suggest that TBOA-sensitive uptake mechanisms are able to
      maintain a steep concentration gradient of glutamate to such a degree that a CA1
      neuron at a depth of 30 microm is exposed to low extracellular glutamate levels
      that are not sufficient to induce a detectable activation of group I mGluRs (< 2
      microM).

PMID- 17498877
TI  - Differences in ultrastructural localization of dopaminergic D1 receptors between
      dorsal striatum and nucleus accumbens in the rat.
AB  - Dopaminergic receptors of the D1 type are highly expressed in the dorsal striatum
      and nucleus accumbens. In the dorsal striatum, they are rarely observed on
      presynaptic terminals. However, their subcellular localization in the nucleus
      accumbens core and shell had not been compared to that of dorsal striatum. Here
      we investigated the subcellular localization of D1 receptors in these three brain
      regions using immunogold labeling and electron microscopy. We showed that, among
      all presynaptic terminals forming asymmetric contact with dendritic processes,
      the percentage of D1R immunoreactive terminals was low in the dorsal striatum
      (8.2%), but reached in the nucleus accumbens core and shell 25.5 and 29%,
      respectively. These observations are consistent with electrophysiological
      studies, which showed that D1 stimulation inhibits the response of target neurons
      to glutamatergic input via presynaptic mechanisms in the nucleus accumbens but
      not in the dorsal striatum.

PMID- 17498878
TI  - The CDC2 I-G-T haplotype associated with the APOE epsilon4 allele increases the
      risk of sporadic Alzheimer's disease in Sicily.
AB  - The cell division cycle 2 (CDC2) gene is a candidate susceptibility gene for
      Alzheimer's disease (AD). We investigated the CDC2 genotype, and allele and
      haplotype frequencies in AD patients and matched controls, distinguishing between
      apolipoprotein E (APOE) epsilon4 allele carriers and non-carriers. APOE epsilon4
      is an established predictor of AD risk. APOE and CDC2 genotypes were examined in
      109 sporadic AD patients and in 110 healthy age- and sex-matched controls from
      Sicily. The epsilon4 allele of APOE was predictive of AD risk in our study group
      (odds ratio: 5.37, 95% CI 2.77-10.41; P<0.0001). Genotype and allele frequencies
      of the three tested CDC2 polymorphisms (Ex6+7I/D, Ex7-15 G>A, Ex7-14 T>A) were
      not significantly different between AD patients and controls. However, a
      significant different distribution of a specific CDC2 haplotype (I-G-T) was found
      between AD patients and controls when analyzing APOE epsilon4-positive subjects
      (P=0.0288). Moreover, the combined presence of the I-G-T haplotype and the
      epsilon4 allele almost doubled the risk of AD (odds ratio: 10.09, 95% CI 3.88
      26.25; P<0.0001) compared to carriers of epsilon4 alone. This study suggests that
      the I-G-T haplotype of the CDC2 gene increases the risk of AD in APOE epsilon4
      carriers.

PMID- 17498879
TI  - Chronic low back pain: physical training, graded activity with problem solving
      training, or both? The one-year post-treatment results of a randomized controlled
      trial.
AB  - Several treatment principles for the reduction of chronic low back pain
      associated disability have been postulated. To examine whether a combination of a
      physical training and an operant-behavioral graded activity with problem solving
      training is more effective than either alone in the long-term, a cluster
      randomized controlled trial was conducted. In total 172 patients, 18-65 years of
      age, with chronic disabling non-specific low back pain referred for
      rehabilitation treatment, were randomized in clusters of four consecutive
      patients to 10 weeks of aerobic training and muscle strengthening of back
      extensors (active physical treatment; APT), 10 weeks of gradual assumption of
      patient relevant activities based on operant-behavioral principles and problem
      solving training (graded activity plus problem solving training; GAP), or APT
      combined with GAP (combination treatment; CT). The primary outcome was the Roland
      Disability Questionnaire adjusted for centre of treatment, cluster, and baseline
      scores. Secondary outcomes were patients' main complaints, pain intensity, self
      perceived improvement, depression and six physical performance tasks. During the
      one-year follow-up, there were no significant differences between each single
      treatment and the combination treatment on the primary outcome, the Roland
      Disability Questionnaire. Among multiple other comparisons, only one significant
      difference emerged, with GAP and APT showing higher self-perceived improvement
      than CT. We conclude that the combination treatment integrating physical, graded
      activity with problem solving training is not a better treatment option for
      patients with chronic low back pain.

PMID- 17498880
TI  - Comparing FAMACHA eye color chart and Hemoglobin Color Scale tests for detecting
      anemia and improving treatment of bovine trypanosomosis in West Africa.
AB  - African animal trypanosomosis (AAT) is considered the most important cattle
      disease in sub-Saharan Africa but its diagnosis in the field is difficult,
      resulting in inappropriate treatments, excessive delay in treatments and under
      treatment. A field study in West Africa investigated the usefulness of anemia in
      the diagnosis of trypanosomosis. A total of 20,772 cattle blood samples were
      taken from 121 villages in 3 countries. The average packed cell volume (PCV) of
      trypanosomosis positive cattle was 23%, versus 28% for negative cattle. In a sub
      set of animals, other causes of anemia were investigated showing most of the
      anemia burden was attributable to trypanosomosis. Anemia was a reasonably
      accurate indicator of trypanosomosis in the study area, with a sensitivity of 56%
      and a specificity of 80% and a diagnostic odds ratio of 4.2, the highest of all
      the signs evaluated (anemia, emaciation, staring coat, lymphadenopathy, fever,
      lacrimation and salivary or nasal discharge). Having confirmed the usefulness of
      anemia as a predictor of trypanosomosis, two potential pen-side tests for anemia
      were evaluated (the first reported trial of their use in cattle), firstly a color
      chart developed for anemia detection in sheep through visual inspection of
      conjunctival membranes (FAMACHA) and secondly the Hemoglobin Color Scale (HbCS)
      developed for assessing hemoglobin levels in human patients by comparing blood
      drops on filter paper with color standards. In a population of cattle suspected
      by their owners to be sick with trypanosomosis (n=898) the sensitivity of the
      HbCS test was 56% and the specificity was 77%, while the sensitivity of the
      FAMACHA test was 95% and the specificity was 22%. The higher sensitivity but
      lower specificity suggests the FAMACHA may be useful as a screening test and the
      HbCS as a confirmatory test. The two tests were also evaluated in cattle randomly
      selected from the village herd. Using cut-off points to optimize test
      performance, the HbCS test had a sensitivity of 81% and a specificity of 62%
      (n=505 cattle), while the FAMACHA had a sensitivity of 92% and a specificity of
      30% (n=298 cattle). Recommendations are made for the appropriate use of these
      tests in the West African region.

PMID- 17498881
TI  - Dynamics of actin filaments during tension-dependent formation of actin bundles.
AB  - The actin cytoskeleton stress fiber is an actomyosin-based contractile structure
      seen as a bundle of actin filaments. Although tension development in a cell is
      believed to regulate stress fiber formation, little is known for the underlying
      biophysical mechanisms. To address this question, we examined the effects of
      tension on the behaviors of individual actin filaments during stress fiber (actin
      bundle) formation using cytosol-free semi-intact fibroblast cells that were pre
      treated with the Rho kinase inhibitor Y-27632 to disassemble stress fibers into a
      meshwork of actin filaments. These filaments were sparsely labeled with quantum
      dots for live tracking of their motions. When ATP and Ca(2+) were applied to the
      semi-intact cells to generate actomyosin-based forces, actin meshwork in the
      protruded lamellae was dragged toward the cell body, while the periphery of the
      meshwork remained in the original region, indicating that centripetally directed
      tension developed in the meshwork. Then the individual actin filaments in the
      meshwork moved towards the cell body accompanied with sudden changes in the
      direction of their movements, finally forming actin bundles along the direction
      of tension. Dragging the meshwork by externally applied mechanical forces also
      exerted essentially the same effects. These results suggest the existence of
      tension-dependent remodeling of cross-links within the meshwork during the
      rearrangement of actin filaments, thus demonstrating that tension is a key player
      to regulate the dynamics of individual actin filaments that leads to actin bundle
      formation.

PMID- 17498882
TI  - Acetone associated inhalation injury and rhabdomyolysis.

PMID- 17498883
TI  - Deep brain stimulation of the lateral habenula in treatment resistant major
      depression.
AB  - The burden of depression as a severe illness with high suicidality and prevalence
      is immense. Despite substantial advancement in psychopharmacology and
      psychotherapy over the last decades a residual group of very ill patients with a
      chronic disease and high suicidal risk remains. Modern theories about the
      pathophysiology of depression are derived from studies examining the mechanism of
      antidepressants influencing the serotonergic (5-HT) and noradrenergic (NE)
      systems. Serotonergic fibers originate from the dorsal raphe nuclei (DRN),
      noradrenergic fibers from the locus coeruleus (LC). Both nuclei represent
      relatively small brain regions and both are controlled to some extent by the
      habenular complex. We propose the hypothesis of an overactivation of the habenula
      in human major depressive episodes (MDE's). Increased activation of the lateral
      habenular nucleus leads to the down regulation of the serotonergic,
      noradrenergic, dopaminergic systems and stimulation of the hypothalamic-pituitary
      adrenal (HPA) axis. Functional inhibition of the lateral habenula via deep brain
      stimulation (DBS) has antidepressive properties. The hypothesis is based on the
      findings of a clinical imaging study examining the habenular after tryptophan
      depletion and on several animal studies which are discussed. Providing that our
      hypothesis will be validated by an analogous tyrosine depletion study and
      additional preclinical studies, the next logical step would be to directly test
      our hypothesis in patients. Possible criteria for patient selection, ethical
      issues and locus of DBS are carefully discussed.

PMID- 17498884
TI  - A new approach using tissue alkaline phosphatase histochemistry to identify
      Crohn's disease.
AB  - In the present study, we investigate intestinal alkaline phosphatase activity in
      mucosal biopsies in patients with inflammatory bowel disease. Crohn's disease
      influences the alkaline phosphatase activity in the intestine, increasing its
      activity. We present a histochemistry-based method for alkaline phosphatase that
      is useful for the identification of Crohn's disease and the differentiation of
      ulcerative colitis.

PMID- 17498885
TI  - P16(INK4a) overexpression independent of Human Papilloma Virus (HPV) infection in
      rare subtypes of endometrial carcinomas.
AB  - In the current study, we evaluated p16 expression in rare subtypes of endometrial
      carcinomas, whose HPV status has been previously examined in order to establish
      the role of this protein in their pathogenesis. These rare subtypes of
      endometrial carcinomas are primary squamous endometrial carcinoma (ESCC),
      endometrial mucinous microglandular adenocarcinoma (EMMA), and endometrial
      transitional cell carcinoma (ETCC). All tissues, obtained at the time of
      hysterectomy, were fixed in 10% phosphate-buffered formalin and embedded in
      paraffin. Serial sections were made for hematoxylin and eosin staining and for
      immunohistochemistry. Although a previous PCR study has demonstrated that none of
      these neoplasms showed any signal for HPV DNA, these malignancies did display
      immunoreactivity for P16(INK4a). In ESCC, P16(INK4a) immunoreactivity was diffuse
      in 100% of neoplastic cells. In two cases of EMMA, positivity for P16INK4a was
      zonal. In ETCC, scattered cells were positive for P16INK4a protein. These
      findings suggest that alteration of p16 could play an etiologic role, without any
      association to HPV infections, in these rare endometrial carcinomas. However, in
      our view, other cases of these rare malignancies should be investigated in order
      to confirm this hypothesis.

PMID- 17498886
TI  - Racial differences in CYP3A4 genotype and survival among men treated on Radiation
      Therapy Oncology Group (RTOG) 9202: a phase III randomized trial.
AB  - PURPOSE: Inherited genotypes may explain the inferior outcomes of African
      American (AA) men with prostate cancer. To understand how variation in CYP3A4
      correlated with outcomes, a retrospective examination of the CYP3A4 *1B genotype
      was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02.
      METHODS AND MATERIALS: From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54
      (4.3%) of 1,274 European American (EA) patients. All patients received goserelin
      and flutamide for 2 months before and during RT (STAD-RT) +/- 24 months of
      goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events
      studied included overall survival and biochemical progression using American
      Society for Therapeutic Radiology and Oncology consensus guidelines. RESULTS:
      There were no differences in outcome in patients in with or without CYP3A4 data.
      There was an association between race and CYP3A4 polymorphisms with 75% of EAs
      having the Wild Type compared to only 25% of AA men (p <0.0001). There was no
      association between CYP3A4 classification or race and survival or progression.
      CONCLUSIONS: The samples analyzed support previously reported observations about
      the distribution of CYP3A4 *1B genotype by race, but race was not associated with
      poorer outcome. However, patient numbers were limited, and selection bias cannot
      be completely ruled out.

PMID- 17498887
TI  - Radiation oncologists in the United States.
AB  - PURPOSE: To provide an extensive and detailed portrait of radiation oncologists,
      their professional activities, and the practices in which they work. METHODS AND
      MATERIALS: We analyzed non-individually identified data from the American College
      of Radiology's 2003 Survey of Radiation Oncologists, a stratified random sample
      survey that guaranteed respondents' confidentiality and achieved a 68% response
      rate, with a total of 472 responses. Responses were weighted to make them
      representative of all radiation oncologists in the United States. We use two
      tailed z tests of percentages and means to compare information from the current
      survey with those from a similar 1995 survey. RESULTS: The number of
      posttraining, professionally active radiation oncologists grew from nearly 2900
      in 1995 to nearly 3500 in 2003, an increase of approximately 21%. Twenty-three
      percent of posttraining, professionally active radiation oncologists were women.
      Among posttraining, professionally active radiation oncologists, 95% were board
      certified. Forty-eight percent of radiation oncologists were in nonacademic,
      radiation-oncology-only private practices; 20% in academic practice; 14% in
      nonacademic, multispecialty practices; and 11% in solo practice. The largest
      percentage of radiation oncologists worked in the South (34%). The average annual
      number of patients treated (curative and palliative) per radiation oncologist was
      264. On average, radiation oncologists preferred a 4% increase in their workload.
      The proportion of radiation oncologists planning a career change decreased from
      8% in 1995 to 4% in 2003, and in 2003 34% said they were enjoying radiation
      oncology more than 5 years earlier, compared with 21% in 1995. CONCLUSION:
      Despite concerns in 2003 about lower-than-optimal workload, professional
      satisfaction, if anything, increased since 1995.

PMID- 17498888
TI  - Antimicrobial activity of Diospyros anisandra.
AB  - Leaves, root and stem bark of Diospyros anisandra were screened against two
      strains of Mycobacterium tuberculosis, one resistant and one susceptible to
      antibiotics, using the microplate Alamar blue assay test. The lypophylic
      fractions of the root and bark showed significant inhibitory activity against
      both strains, with the hexane fraction of the bark showing the strongest activity
      (MIC 6.25 microg/ml) against the resistant strain and a significant antimicrobial
      activity against Staphylococcus aureus, Bacillus subtilis, Candida albicans,
      Aspergillus niger, and Colletotrichum gloeosporioides. The bioassay-guided
      purification of the bioactive hexane fraction resulted in the isolation and
      identification of the naphthoquinone plumbagin as one of the metabolites
      responsible for the biological activity.

PMID- 17498889
TI  - Hypoglycemic activity of Nymphaea stellata leaves ethanolic extract in alloxan
      induced diabetic rats.
AB  - The ethanolic extract of leaves of Nymphaea stellata given by oral route to
      diabetic rats at dose of 100 and 200 mg/kg/day for seven days reduced
      significantly by 31.6 and 42.6 % the plasma glucose level increased by
      intraperitoneal injection of 120 mg/day of alloxan. Moreover, the treatment
      significantly affected the plasma level of cholesterol and triglyceride.

PMID- 17498890
TI  - A novel water-soluble alpha-(1-->4)-glucan from the root of Cudrania
      tricuspidata.
AB  - CTPS-01, a water-soluble polysaccharide, was obtained from the root of Cudrania
      tricuspidata and estimated to have an average molecular weight of 5.9 x 10(3) and
      to be composed of glucose residues, solely. It contains an average repeating unit
      of decasaccharide, having a backbone consisting of 1,4-linked alpha-D
      glucopyranosyl residues, to which a side chain consisting of terminal and 1,4
      linked alpha-D-glucopyranosyl residues is attached at position O-6 of the
      branching residues.

PMID- 17498891
TI  - [Obstetric management after ectopic pregnancy in the caesarean section scar: a
      case report and review of literature].
AB  - We report the case of a patient who came out pregnancy twelve months after
      medical and surgical treatment of an ectopic pregnancy in a previous caesarean
      section scar. The preconceptional management consisted in a saline infusion
      sonohysterography and a pelvic magnetic resonance imaging. Judging the risks of
      abnormal placental insertion to be higher in this case compared to a simple
      caesarean section, a careful ultrasonography with color doppler imaging was
      carried out. The myometrium fragility caused by the ectopic pregnancy in the
      caesarean section brought us to recommend a prophylactic caesarean section around
      37. The high risks of hemorrhage required a medical center with embolization
      possibilities. A review of literature in order to define the medical care adapted
      in this case was come out.

PMID- 17498892
TI  - A novel spectral tuning in the short wavelength-sensitive (SWS1 and SWS2)
      pigments of bluefin killifish (Lucania goodei).
AB  - The molecular bases of spectral tuning in the UV-, violet-, and blue-sensitive
      pigments are not well understood. Using the in vitro assay, here we show that the
      SWS1, SWS2-A, and SWS2-B pigments of bluefin killifish (Lucania goodei) have the
      wavelengths of maximal absorption (lambda(max)'s) of 354, 448, and 397 nm,
      respectively. The spectral difference between the SWS2-A and SWS2-B pigments is
      largest among those of all currently known pairs of SWS2 pigments within a
      species. The SWS1 pigment contains no amino acid replacement at the currently
      known 25 critical sites and seems to have inherited its UV-sensitivity directly
      from the vertebrate ancestor. Mutagenesis analyses show that the amino acid
      differences at sites 44, 46, 94, 97, 109, 116, 118, 265, and 292 of the SWS2-A
      and SWS2-B pigments explain 80% of their spectral difference. Moreover, the
      larger the individual effects of amino acid changes on the lambda(max)-shift are,
      the larger the synergistic effects tend to be generated, revealing a novel
      mechanism of spectral tuning of visual pigments.

PMID- 17498893
TI  - Comparative quantification of the in vitro activity of veterinary
      fluoroquinolones.
AB  - The aim of this study was to compare the in vitro antimicrobial activity of the
      veterinary fluoroquinolones against a panel of recently isolated porcine and
      bovine bacterial pathogens. The study used enrofloxacin as a benchmark against
      which other agents were compared, being the most common fluoroquinolone used in
      treatment of bovine and porcine infections. The activity of ciprofloxacin was
      also assessed as it is the main metabolite of enrofloxacin in cattle.
      Enrofloxacin and ciprofloxacin generally showed higher antibacterial activity, in
      terms of MIC(50) values, for most pathogen species when compared with
      marbofloxacin, difloxacin, danofloxacin and norfloxacin. Ciprofloxacin showed
      significantly greater in vitro antibacterial activity than enrofloxacin against
      M. haemolytica, P. multocida and E. coli, whereas enrofloxacin showed greater
      activity than ciprofloxacin against S. aureus. Marbofloxacin was significantly
      more active than enrofloxacin against M. haemolytica, E. coli and B.
      bronchiseptica but less active against P. multocida, S. aureus, coagulase
      negative Staphylococci, S. dysgalactiae, S. uberis, A. pleuropneumoniae and S.
      suis. Danofloxacin was significantly less active than enrofloxacin against P.
      multocida, E. coli, S. uberis, A. pleuropneumoniae and S. suis. Enrofloxacin and
      its metabolite ciprofloxacin showed the highest in vitro activities against most
      bovine pathogens tested and the porcine pathogens also showed a high degree of
      sensitivity to enrofloxacin. These data facilitate further
      pharmacokinetic/pharmacodynamic comparison of fluoroquinolones currently used in
      veterinary medicine.

PMID- 17498894
TI  - Therapeutic approaches targeting the prion receptor LRP/LR.
AB  - Transmissible spongiform encephalopathies known as prion diseases are a group of
      fatal neurodegenerative disorders that affect both humans and animals. The
      generally accepted principle of the disease is that the conversion of the
      cellular prion protein (PrP(c)) into the disease associated isoform PrP(Sc) leads
      to spongiform degeneration of the brain and amyloid plaque formation. Until now
      no therapy leading to potential alleviation or even cure of the disease exists.
      It is therefore important to develop therapeutic approaches for the treatment of
      TSEs since these infections are inevitably fatal and, especially in the case of
      vCJD, they affect youngsters. Besides current conventional therapeutic
      strategies, this review summarizes new therapeutic tools targeting the prion
      receptor LRP/LR.

PMID- 17498895
TI  - Molecular characterisation of 12 Chlamydophila felis polymorphic membrane protein
      genes.
AB  - A group of genes thought to encode members of the unique chlamydial polymorphic
      membrane protein (pmp) family were recently described in the Chlamydophila felis
      genome. This study aimed to commence characterisation of a subset of 12 of these
      putative pmp genes by developing and using gene-specific real-time (Q)PCR assays
      to confirm their presence in a wide range of C. felis field isolates and
      laboratory strains, and to look for pmp mRNA expression during in vitro
      infection. Sequencing of 525-698 base pair regions of pmp genes 7, 9-11, 13-20
      for two laboratory strains of C. felis and alignment with the published Fe/C-56
      sequence found only a single nucleotide polymorphism present in pmp9. Following
      the development of gene-specific (Q)PCR assays, analysis of genomic DNA extracted
      from 40 C. felis field isolates and 4 laboratory strains found that all 12 pmp
      genes were represented in all cases. Reverse transcription (RT)-QPCR analysis of
      RNA extracted from cell cultures at 24 and 48 h post inoculation with 1 of 5
      different strains of C. felis detected transcripts for all 12 pmp genes at both
      time points. Analysis of the relative levels of pmp gene transcription suggested
      that down-regulation of the expression of multiple C. felis pmp genes occurs
      between 24 and 48 h post inoculation. This study provides the first evidence that
      12 of the putative pmp C. felis genes are transcribed during in vitro infection,
      and shows that these genes are present in a large range of C. felis field
      isolates and multiple passage laboratory-grown strains.

PMID- 17498896
TI  - mRNA-induction and cytokine release during in vitro exposure of human nasal
      respiratory epithelia to methyl methacrylate.
AB  - BACKGROUND: Methyl methacrylate (MMA) has been reported to cause
      histopathological changes in rodent nasal epithelium after inhalation challenges.
      Data in humans are lacking. METHODS: In this in vitro design 22 primary cell
      cultures taken from inferior turbinate tissue of healthy individuals were exposed
      to MMA concentrations of 50 ppm (German MAK-value) and 200 ppm. mRNA expression
      and cytokine release of inflammatory mediators were quantified after 4h and after
      24h. Controls were exposed to synthetic air. Q-PCR analysis was performed for TNF
      alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2. ELISA assays were
      performed from culture supernatants for TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1
      and GMCSF. RESULTS: Acute inductions of mRNA after 4h were observed for TNF
      alpha, IL-1beta, IL-6, IL-8 and MCP-1 at 50 ppm. ELISA analysis of the described
      parameters did not reveal any significant upregulations at both concentrations
      after both 4h and 24h. CONCLUSIONS: The obtained data suggest that exposure of
      human respiratory epithelia in vitro to 50 ppm and to 200 ppm of MMA does not
      induce lasting upregulation of the inflammatory mediators measured in this study.
      The exposure limit of 50 ppm appears safe following these results obtained from
      human respiratory epithelia.

PMID- 17498897
TI  - New analytical techniques to facilitate preformulation screening in propellant
      systems.
AB  - The objective of these studies was to investigate the applicability of an online
      direct inject HPLC method for the preformulation screening of pharmaceutical
      agents in pressurized metered dose inhalers (MDIs). The technique was initially
      utilized for the solubility determination of solid solutes. This study explores
      the extension of the online direct inject method for the evaluation of drug
      stability in propellant systems as well as for the analysis of MDI vials crimped
      with metered valves. Through-life content analysis confirmed that a single vial
      may be repeatedly sampled, thus facilitating the stability evaluation of a single
      unit over time. The method was successfully used for evaluating the stability of
      a model drug, as a function of several different formulation configurations, with
      minimal sample numbers. Additionally, studies determined that after modifications
      were made to the injection coupler, the technique was also feasible for use with
      50 and 100 microL metered valves, however further modifications are necessary for
      25 microL valves.

PMID- 17498898
TI  - Liquisolid technique for dissolution rate enhancement of a high dose water
      insoluble drug (carbamazepine).
AB  - Different liquisolid formulations of carbamazepine were accomplished by
      dissolving the drug in the non-toxic hydrophilic liquids, and adsorbing the
      solution onto the surface of silica. In order to reduce the amounts of carrier
      and aerosil in liquisolid formulations, some additives namely
      polyvinylpyrrolidone (PVP), hydroxypropyle methylcellulose (HPMC) and
      polyethylene glycol (PEG 35000) were added to liquid medication to increase
      loading factor. The effects of various ratios of carrier to coating material, PVP
      concentration, effect of aging and type of the carrier on dissolution rate of
      liquisolid compacts were studied. X-ray crystallography and differential scanning
      calorimetery (DSC) were used for evaluation of physicochemical properties of
      carbamazepine in liquisolid formulations. The results showed that the drug
      loading factor was increased significantly in the presence of additives.
      Liquisolid formulations containing PVP as additive, exhibited significantly
      higher drug dissolution rates compared to the compacts prepared by the direct
      compression technique. It was shown that microcrystalline cellulose had more
      liquid retention potential in comparison with lactose, and the formulations
      containing microcrystalline cellulose as carrier, showed higher dissolution rate.
      By decreasing the ratio of microcrystalline cellulose to silica from 20 to 10, an
      improvement in dissolution rate was observed. Further decrease in the ratio of
      microcrystalline cellulose:silica from 10 to 5 resulted in a significant
      reduction in dissolution rate. Increasing of PVP concentration in liquid
      medication caused a dramatic increase in dissolution rate at first 30min. The
      results showed that the dissolution rate of liquisolid tablets was not
      significantly affected by storing the tablets at 25 degrees C/75% relative
      humidity for a period of 6 months. The results of DSC and X-ray crystallography
      did not show any changes in crystallinity of the drug and interaction between
      carbamazepine and exipients during the process.

PMID- 17498899
TI  - The Finnish legislation on workplace drug testing.
AB  - In Finland, the Act on the Protection of Privacy in Working Life (759/2004) that
      entered into force in 2004 incorporates provisions related to drug use testing,
      e.g. on the employers' right to process in certain situations information on job
      applicants' and employees' drug use. In the same context, provisions were added
      to the Occupational Health Care Act (1383/2001) on the employer's obligation to
      draw up, together with the staff, a written programme dealing with alcohol and
      drugs for the workplace. The programme defines the overall objectives for and the
      practices to be observed at the workplace in order to prevent substance abuse and
      to refer the problem users to treatment. The Occupational Health Care Act also
      includes provisions on drug tests and the drug test certificate as well as on
      reimbursement of the expenses of drug tests. Furthermore, the Act lays down a
      definition of drug tests. Every workplace shall have a plan/programme on drug
      free workplace, where the jobs in which the workers have to present a drug test
      certificate to the employer must be defined. This plan/programme shall be
      discussed in cooperation on tripartite basis at the workplace. A Government
      decree on drug use testing (218/2005) has been issued in virtue of the
      Occupational Health Care Act. It lays down provisions on the practical
      performance of drug tests, i.e. taking and analysis of samples, and
      interpretation of the test results. The purpose of the Government decree is to
      ensure that workplace drug testing is carried out in a way presupposed by a good
      occupational health care practice and the laboratory quality standards, taking
      into account the integrity and protection of privacy of the persons tested as
      well as their other fundamental rights.

PMID- 17498900
TI  - [Is obliterating arteriopathy of the lower limbs still the poor member of the
      arterial disease family? What can be done?].

PMID- 17498901
TI  - [Quality and usefulness of an anonymous unique personal identifier to link
      hospital stays recorded in French claims databases].
AB  - BACKGROUND: Since 2001, the French national case mix program is allowed by law to
      use an enciphering algorithm named "FOIN" to produce a unique anonymous
      identifier in order to crosslink, within and across hospitals, discharge
      abstracts from a given patient. This algorithm "thrashes" the person's health
      insurance number, date of birth and gender. Before using information produced by
      the case mix program, either for case mix payment or for epidemiology research or
      for assessing care approaches, the quality of linkage must be evaluated. METHODS:
      Foin error flags were first assessed in the 2002 Rhone-Alpes regional case mix
      database. Second, for the two university hospitals of Lyon and Saint-Etienne,
      double identifiers (two or more Foin identifiers for the same patient) and
      collisions (a single Foin identifier for at least two patients) were compared
      with others identifiers: administrative identifier and an anonymous identifier
      produced by Anonymat software from name, forename and date of birth. Third, Foin
      error flags are crossed with Foin double identifier or collision mistakes.
      RESULTS: First, among 1,668,971 hospital discharge abstracts from the regional
      case mix database, 206,710 (12.4%) had at least one Foin error flag. The most
      frequent error flag (93026 [5.5%] stays) was due to the lack of the three
      identifying variables. The greatest number for error flags concerned the stays of
      newborns (38.5%) and those of public hospitals (17.3%). Second, Foin created a
      few double identifiers: 1.2% among 137,236 patients from university hospital of
      Lyon and 0.3% among 39512 patients from university hospital of Saint-Etienne. The
      collisions concerned 7776 (5.7%) patients from Lyon and 460 (1.2%) from Saint
      Etienne. The identifier produced by Anonymat performed better than the one
      produced by Foin: 99.6% from the two university hospitals. Third, less than 3% of
      stays without Foin error flag nevertheless had mistakes on Foin when compared
      with others identifiers. CONCLUSION: The overall assessment is not in favour of a
      quality threshold using the Foin identifier on a routine basis except in some
      areas and if certain activities like neonatology are excluded. There are several
      ways to improve the linkage of health data.

PMID- 17498902
TI  - The value of diffusion-weighted imaging in combination with T2-weighted imaging
      for rectal cancer detection.
AB  - OBJECTIVE: To evaluate the clinical value of diffusion-weighted imaging (DWI) in
      combination with T(2)-weighted imaging (T(2)WI) for the detection of rectal
      cancer as compared with T(2)WI alone. MATERIALS AND METHODS: Forty-five patients
      with rectal cancer and 20 without rectal cancer underwent DWI with parallel
      imaging and T(2)WI on a 1.5 T scanner. Images were independently reviewed by two
      readers blinded to the results to determine the detectability of rectal cancer.
      The detectability of T(2)W imaging without and with DW imaging was assessed by
      means of receiver operating characteristic analysis. The interobserver agreement
      between the two readers was calculated with kappa statistics. RESULTS: The ROC
      analysis showed that each of two readers achieved more accurate results with
      T(2)W imaging combined with DW imaging than with T(2)W imaging alone
      significantly. The A(z) values for the two readers for each T(2)WI and T(2)WI
      combined with DWI were 0.918 versus 0.991 (p=0.0494), 0.934 versus 0.997
      (p=0.0475), respectively. The values of kappa were 0.934 for T(2)WI and 0.948 for
      T(2)WI combined with DWI between the two readers. CONCLUSION: The addition of DW
      imaging to conventional T(2)W imaging provides better detection of rectal cancer.

PMID- 17498903
TI  - Comparison of left and right ventricular volume measurement using the Simpson's
      method and the area length method.
AB  - PURPOSE: To compare ventricular volume measurement using a volumetric approach in
      the three standard cardiac planes and ventricular volume estimation by a
      geometrical model, the Area-Length method (ALM). MATERIALS AND METHODS: Fifty-six
      healthy volunteers were examined (27 males, 29 females) on a 1.5T MR-unit with
      ECG-triggered steady state free precision (SSFP) Cine-MR sequences and parallel
      image acquisition. Multiple slices in standardized planes including the short
      axis view (sa), 4-chamber view (4ch), left and right 2-chamber views (2ch) were
      used to cover the whole heart. End-systolic and end-diastolic ventricular volumes
      (EDV, ESV), stroke volume (SV), and ejection fraction (EF) were calculated with
      Simpson's rule in all planes and with ALM in the 2ch and 4ch planes. Global
      function parameters measured in the sa plane were compared with those obtained in
      the other imaging planes. RESULTS: A very good correlation is observed when
      comparing functional parameters calculated with Simpson's rule in all imaging
      planes: for instance, the mean EDV/ESV of the left and right ventricle of the
      female population group measured in sa, 4ch, and 2ch: left ventricle EDV/ESV
      114.3/44.4, 120.9/46.5, and 117.7/45.3 ml; right ventricle EDV/ESV 106.6/46.0,
      101.2/41.1, and 103.5/43.0 ml. Functional parameters of the left ventricle
      calculated with ALM in 2ch and 4ch correlate to parameters obtained in sa with
      Simpson's rule in the range of 5-10%: for instance, the EDV/ESV of the left
      ventricle of the male population group measured in the sa, 4ch, and 2ch:
      160.3/63.5, 163.1/59.0, and 167.0/65.7 ml. Functional parameters of the right
      ventricle measured with ALM in 4ch are 40-50% lower and calculated in 2ch almost
      double as high as compared with the parameters obtained in sa with Simpson's
      rule: for instance, male right ventricular EDV/ESV measured in sa, 4ch, and 2ch:
      153.4/68.1, 97.5/34.5, and 280.2/123.2 ml. The EF correlates for all imaging
      planes measured with the Simpson's rule in both ventricles and using ALM in the
      left ventricle except for males with an overestimation of less than 6%. The EF of
      the right ventricle is calculated higher using ALM in 4ch and 2ch compared to the
      EF calculated in sa: female/male EF of the right ventricle measured in the sa,
      4ch, and 2ch: 56.8/55.7, 66.0/65.0, and 60.0/57.0%. CONCLUSION: In the setting of
      healthy volunteers the ALM method should not be used in 2ch and 4ch planes of the
      right ventricle because of lacking correlation of global functional parameters
      compared to those obtained in the sa plane. Using Simpson's rule functional
      parameters correlate well to each other in the different imaging planes.

PMID- 17498904
TI  - Lumbosacral osseous tumors in children.
AB  - A wide variety of benign and malignant neoplasms in children involve the
      lumbosacral region. When a solitary lesion of the lower spine occurs, tumors or
      tumor-like lesions represent an important group of entities for diagnostic
      consideration. Diagnostic investigation should begin with a patient history,
      physical examination, laboratory testing, and radiography. Roentgenograms, which
      demonstrate bone deviations, should be used as an initial examination. The
      results should direct further imaging studies, such as computed tomography (CT),
      magnetic resonance imaging (MRI), and bone scintigraphy. CT should be the chosen
      modality for delineating tumoral osteoid matrix formation. MRI shows soft-tissue
      masses and medullary infiltration better than any other radiological modality. A
      multimodal radiological approach is helpful in the overall evaluation and
      differential diagnosis of vertebral lesions in children. Although imaging
      features, especially of benign lesions, may yield a high percentage of accurate
      diagnoses, in cases with radiological findings highly suggestive of malignancy, a
      specific diagnosis cannot always be made, and histopathological findings are
      essential to achieve the diagnosis that will guide the therapy.

PMID- 17498905
TI  - Morphological changes of ulcerative plaque in patients received carotid
      angioplasty and stenting (CAS).
AB  - BACKGROUND: Carotid ulceration plaque is a strong risk factor for stroke and
      systemic vascular events. The purpose of this study was to assess immediate and
      follow-up ulcer morphology after carotid angioplasty and stenting (CAS). METHODS
      AND RESULTS: A total of 124 patients were included in the study. Ulcerative
      plaques were identified in 92 arteries from 81 patients (21% were asymptomatic
      and 79% symptomatic). The ulcer disappeared immediately after stenting in 36
      (39%) of 92 arteries in 50 patients. Patients with initial mild degree of
      stenosis (50-69% stenosis) prior to stent, Type-3 and Type-4 ulcers were more
      prone to have residual ulcers immediate after stenting procedure. Ulcers located
      distal and proximal to the site of maximal stenosis, and ulcers extending outside
      of the imaginary line connecting the distal and proximal normal borders of the
      carotid artery were also more likely to have residual ulcers (P<0.001). Follow-up
      angiograms (mean time after CAS=10.1 months, range=3-28 months) performed in 32
      arteries (29 patients) revealed that residual ulceration disappeared in 17
      lesions (53%) and became smaller in 15 lesions (47%). During follow-up,
      ipsilateral neurological symptoms were not evident in any of the 29 patients
      (mean time after CAS=20.1 months, range=9-41 months). CONCLUSIONS: Ulceration
      morphology, and stenosis severity prior to stent procedure had an impact on ulcer
      coverage after CAS. Our findings suggest that residual ulcers disappear or
      improve over time and that with appropriate medication, will not lead to embolic
      strokes.

PMID- 17498906
TI  - Percutaneous laser ablation of unresectable primary and metastatic adrenocortical
      carcinoma.
AB  - PURPOSE: To evaluate the feasibility, safety, and clinical benefits of
      percutaneous laser ablation (PLA) in patients with unresectable primary and
      metastatic adrenocortical carcinoma (ACC). PATIENTS AND METHODS: Four patients
      with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound
      guided PLA. In one case the procedure was performed also on the primary tumor.
      RESULTS: After three sessions of PLA, the primary tumor of 15 cm was ablated by
      75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2
      to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by
      75%. There were no major complications. Treatment resulted in an improvement of
      performance status and a reduction of the daily dosage of mitotane in all
      patients. The three patients with liver metastases presented a marked decrease of
      24-h urine cortisol levels, an improved control of hypertension and a mean weight
      loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48
      months), two patients have died of tumor progression, while two other patients
      remain alive and free of disease. CONCLUSIONS: Percutaneous laser ablation is a
      feasible, safe and well tolerated procedure for the palliative treatment of
      unresectable primary and metastatic ACC. Further study is required to evaluate
      the impact of PLA on survival.

PMID- 17498907
TI  - Two-phase partitioning bioreactors for treatment of volatile organic compounds.
AB  - Two-phase partitioning bioreactors (TPPBs) allow the biological removal of
      volatile organic compounds (VOCs) from contaminated gas streams at unprecedented
      rates and concentrations. TPPBs are constructed by adding a non-aqueous phase
      (e.g. hexadecane, silicone oil) to an aqueous phase that contains the
      microorganisms responsible for degrading the VOCs. Presence of a water-immiscible
      phase improves the transfer of hydrophobic substrates (e.g. hexane, oxygen) or
      reduces the toxicity of inhibitory substances (e.g. benzene, toluene) to the
      microorganisms present in the aqueous phase. The non-aqueous phase is selected
      based on cost, safety, good partitioning properties towards the target
      pollutants, biocompatibility, and non-biodegradability. TPPBs have hitherto been
      designed as laboratory-scale well-mixed stirred-tank reactors or as biofilters
      that contain a non-aqueous phase. Scale-up and industrial use of TPPBs require
      elucidation and modeling of the mechanisms of substrate transfer and uptake;
      understanding of the mechanisms of microbial selection; identification or
      synthesis of new inexpensive and robust non-aqueous phases; and generation of
      suitable guidelines for process design and control.

PMID- 17498908
TI  - The denial of cancer interview: development and first assessment of psychometric
      properties in lung cancer patients.
AB  - OBJECTIVE: Based on Weissman and Hackett's comprehensive definition of denial, a
      semi-structured interview was developed to measure denial in cancer patients. The
      denial in cancer interview (DCI) covers both the patients' recount of their
      illness experience and the expert's impression of the level of denial in the
      patient story. This paper describes the development and first psychometric
      analyses of the instrument. METHOD: The development of the DCI was based on
      clinical observation, the expert opinion of eight specialised psychiatrist as
      well as three small pilot studies to assess feasibility. The DCI is composed of
      two parts: a semi-structured interview consisting of nine specific items to be
      answered by the patient and two items covering the interviewer's clinical
      impression of the patient's type and level of denial. Follow-up interviews were
      held at 8, 16 and 32 weeks after the baseline assessment (T2-4). To measure the
      inter-rater reliability, interviews were recorded and rated independently by one
      interviewer and one of the study's co-workers. RESULTS: One hundred and ninety
      five consecutive newly diagnosed lung cancer patients were interviewed. The
      internal consistency of the DCI (Cronbach's alpha) was 0.84 at first interview
      and 0.85, 0.82 and 0.83 at T2-4, respectively. The inter-rater agreement was good
      for the DCI overall and the patient's assessment scale, and satisfactory for the
      clinical impression items. Content validity was supported by clinical
      observation, in depth open interviewing and expert opinion. CONCLUSION: The DCI
      proved to be a feasible and reliable instrument for measuring denial in lung
      cancer patients. Further testing in other oncology settings will provide insight
      in wider applicability. PRACTICE IMPLICATIONS: The DCI can be used in future
      studies concerning denial in cancer patients. Insight in denial and its
      background will help us to adequately address denial in patients and communicate
      with them.

PMID- 17498909
TI  - Radioguided Intraoperative Margins Evaluation (RIME): preliminary results of a
      new technique to aid breast cancer resection.
AB  - AIMS: Women undergoing breast-conserving surgery for cancer can present residual
      disease. We have developed a technique called Radioguided Intraoperative Margins
      Evaluation (RIME) that uses a radiopharmaceutical to distinguish normal and
      cancer tissues. The aim of this study was to assess whether RIME is a feasible
      technique, and if it could help in breast cancer resection with free margins,
      minimizing residual disease. METHODS: Twenty-three breast cancer patients
      programmed for mastectomy were selected. Before surgery, the patients were
      submitted to scintimammography with 99mTc-sestamibi to estimate the optimal time
      to begin radioguided surgery. Twenty patients were submitted to magnetic
      resonance imaging (MRI), to evaluate skin, deep fascia and to detect other tumor
      foci. At the beginning of the surgery, the same dose of 99mTc-sestamibi was
      intravenously injected into patients. Tumor resection was performed under
      guidance of a gamma-probe, characterizing the RIME technique. Finally, modified
      radical mastectomy was performed. Tumor and residual breast were
      histopathologically examined. RESULTS: The RIME technique was successfully
      performed in all patients. The principal tumor was removed by this technique and
      provided 82.6% of histologically free margins (mean margins, 4.8 mm).
      Additionally, 47.8% of patients were without residual disease. The mean size of
      residual carcinoma was 3.67 mm and generally located near the tumor bed (<1.5
      cm). There was no significant association between presence of residual disease
      and tumor size or margin status. CONCLUSION: RIME is a feasible technique that
      could help tumor resection with free margins; however, it seems to be limited for
      small carcinoma foci.

PMID- 17498910
TI  - A metalloproteinase-9 polymorphism which affects its expression is associated
      with increased risk for oral squamous cell carcinoma.
AB  - AIM: In light to recently found contribution of factors associated with
      angiogenesis, thrombosis and inflammation to carcinogenesis, we investigated the
      possible association of metalloproteinase-9 (MMP-9) with increased risk of oral
      cancer. METHODS: In DNA samples of 152 patients with oral squamous cell carcinoma
      and 162 healthy controls of comparable ethnicity, age and sex, we studied the 
      1562 C/T polymorphism in the MMP-9 gene promoter, which affects its
      transcription. RESULTS: The detected frequency for the high expression T allele
      in the patients' group was significantly increased in comparison to that of the
      control group (22% versus 15%, respectively; P<0.05). This difference was due to
      the relative increase of C/T heterozygotes in the group of patients, in
      comparison to controls (P<0.05, 95% OR 1.92, CI 1.21-3.06). The same pattern of
      significance was observed between controls and the subgroups of patients with
      initial (I & II) stages of cancer, without positive family history of cancer or
      thrombophilia, with smoking and alcohol abuse habits. CONCLUSIONS: The
      investigated MMP-9 polymorphism has a strong association with increased risk for
      developing oral cancer in a subset of the general population. These results are
      in accordance to previous studies of constitutive expression and secretion of MMP
      9 in invasive oral carcinoma cell lines. The observation that T allele carriers
      have an increased risk for developing oral cancer only in initial stages, but not
      in advanced ones, may be due to the role of MMP-9 in the inhibition of
      angiogenesis by generating angiostatin from plasminogen.

PMID- 17498911
TI  - Avoidance of axillary lymph node dissection in selected patients with node
      positive breast cancer.
AB  - AIMS: Currently, it is standard practice to avoid ALND in patients with negative
      SLN, whereas this procedure is mandated for those with positive SLN. However,
      there has been some debate regarding the necessity of complete ALND in all
      patients with positive SLN. This review article discusses the issues related to
      eliminating the need for ALND in selected patients with positive nodes. METHODS:
      A review of the English language medical literature was performed using the
      MEDLINE database and cross-referencing major articles on the subject, focusing on
      the last 10 years. RESULTS: Currently, complete ALND is mandated in patients with
      SLN macrometastases as well as those with clinically positive nodes. It is not
      clear whether SLN biopsy is appropriate for axillary staging in patients with
      initially clinically positive nodes (N1) that become clinically node-negative
      (N0) after neoadjuvant chemotherapy. Although there is debate regarding whether
      ALND should be performed in patients with micrometastases in the SLN, it seems
      premature to abandon ALND in clinical practice. Moreover, it remains unclear
      whether it is appropriate to avoid complete ALND in patients with ITC-positive
      SLN alone. CONCLUSIONS: In the absence of data from randomised trials, the long
      term impact of SLN biopsy alone on axillary recurrence and survival rate in
      patients with SLN micrometastases as well as those with ITC-positive SLN remains
      uncertain. These important issues must be determined by careful analysis of the
      results of ongoing clinical trials.

PMID- 17498912
TI  - A comparative study of risk factors and prognostic features between symptomatic
      and screen detected breast cancer.
AB  - AIMS: To compare prognostic factors in screen detected breast cancer (SDBC) and
      symptomatically presenting breast cancer (SBC). METHODS: Data were examined on
      100 SDBC and 100 SBC. Multiple clinical patient factors were assessed including
      histopathological features. Using the Gail model each patient's risk of
      developing breast cancer was calculated and these data were examined for
      differences between groups. RESULTS: There was no difference in the mean age of
      patient presentation or in the risk of breast cancer development between groups
      (2.2% vs. 2.2%, SDBC vs. SBC, actuarial risk of cancer at 5 years). SDBC patients
      had a significantly lower grade (1.95 vs. 2.44, SDBC vs. SBC, P<0.05), a smaller
      size of tumour (15.4mm vs. 29.3mm, SDBC vs. SBC, P<0.05) and a higher rate of
      oestrogen (94% vs. 81%, P<0.05) and progesterone (75% vs. 52%, P<0.05) receptor
      positivity. When compared using the Nottingham Prognostic Index, SDBC was
      associated with a better prognosis (r=-0.444, P<0.001). CONCLUSIONS: Though both
      groups have similar demographics and risk, SDBC patients appear to have more
      favourable prognostic features. This has implications for the application of
      systemic therapy in breast cancer and supports the observation that SDBC is a
      more indolent form of disease.

PMID- 17498913
TI  - Combination blue dye sentinel lymph node biopsy and axillary node sampling: the
      Edinburgh experience.
AB  - AIMS: The sentinel node biopsy technique which is being increasingly used to
      stage breast cancers has limitations regarding not being able to find the blue
      hot node in about 5% of cases and false negative results in 7% of cases. It has
      been suggested this is probably due to tumour blocking the lymphatic channels.
      The four node sampling technique is dependent on the surgeon's ability to find
      abnormal palpable nodes in the axilla without visual or radioactive signal
      directions. We have combined the two techniques with the expectation to improve
      the results. METHOD: The study evaluates the combined technique in 434 patients
      with early breast cancer in a single centre. RESULTS: A blue sentinel node was
      identified in 394 of 434 cases (91.7%), the false negative rate was 2.4%. Thirty
      six patients had no sentinel node identified. Thirteen of these had positive
      nodes in the node sample. CONCLUSION: Axillary node sampling adds to the accuracy
      of the sentinel node biopsy using blue dye. Pathological features suggest that
      the principal cause of false negative sentinel node biopsy is due to blocking of
      the lymphatic channels by the cancer.

PMID- 17498914
TI  - [The anaesthetist's liability and bullfights].
AB  - Whether you are an aficionado or completely uninitiated, everyone has an opinion
      on bull-fighting. The bull-fighter is in constant risk of injury. A medical team
      made up of surgeons, anesthetists, emergency physicians and nurses remains
      present throughout the show. For the anaesthetist and surgeon, a wounded
      bullfighter is an emergency because the vital and functional prognosis are
      engaged. The team must act in conformity with normal practice and the Code of
      Medical Ethics because any lack of coordination between the practitioners is
      punishable by law in the same way as technical fault. Several specific aspects of
      this type of medical procedure should be highlighted: firstly, the legal
      restrictions within the corrida, and secondly, the nature of the medical team,
      which may be comprised of doctors normally based within a public health
      institution and others who practice in a private health establishment. The
      particularity of the situation reveals differences in the system of liability,
      and civil liability must be distinguished from administrative liability: both of
      these allow the victim to obtain compensation for harm caused, but the
      consequences of each are different according to doctor status. The fact that the
      anaesthetists frequently work on a voluntary and benevolent basis does not
      exonerate them from liability. Lastly, a question frequently addressed is whether
      or not the doctor is covered by his professional insurance when he is on ringside
      duty.

PMID- 17498915
TI  - Trichostatin A, sodium butyrate, and 5-aza-2'-deoxycytidine alter the expression
      of glucocorticoid receptor alpha and beta isoforms in Hut-78 T- and Raji B
      lymphoma cell lines.
AB  - The glucocorticoid receptor (GR) is mainly expressed as nine-exon alternatively
      spliced variants, encoding functional GRalpha and nonfunctional GRbeta.
      Overexpression of GRbeta splice variant was found in glucocorticoid-resistant
      patients with some autoimmune diseases and hematological malignancies. Employing
      reverse transcription, real-time quantitative PCR, and western blot analysis, we
      determined an effect of trichostatin A (TSA), sodium butyrate (NaBu) and 5-aza-2'
      deoxycytidine (5-dAzaC) on GRalpha and GRbeta expression in Hut-78 T- and Raji B
      lymphoma cell lines. We found that TSA, NaBu, and 5-dAzaC significantly increase
      the expression of GRalpha transcript and protein, whereas GRbeta transcript and
      protein expression was profoundly decreased in Hut-78 T- and Raji B- lymphoma
      cell lines. Our observation suggests that changes of epigenetic milieu inside
      cells may alter the expression of GRalpha and GRbeta isoforms.

PMID- 17498916
TI  - [Osteoarticular manifestations of Gaucher disease in adults: pathophysiology and
      treatment].
AB  - Gaucher disease frequently has severe osteoarticular manifestations that may be
      disabling. Ischemic phenomena cause the most serious complications and lead to
      irreversible lesions. Aseptic osteonecrosis of the hip is the most disabling
      complication; it causes intense early bone pain and often joint collapse and
      secondary osteoarthritis in young adults. Localized or systemic bone fragility
      explains osteopenia, osteoporosis, and fractures (vertebral collapse with
      irreversible kyphosis causing chronic morbidity). Although no double-blind
      randomized studies have assessed the bone effects of enzyme replacement therapy,
      it has been shown effective in reducing bone pain in about half of all treatment
      naive patients within 1 to 2 years and in improving bone mineral density after 3
      years. In open-label trials, substrate reduction therapy (miglustat) reduced both
      bone pain and bone marrow infiltration. Specific treatment for bone fragility,
      with bisphosphonates for example, should be considered after rigorous
      individualized evaluation and assessment of other risk factors.

PMID- 17498917
TI  - Homozygosity mapping approach identifies a missense mutation in equine
      cyclophilin B (PPIB) associated with HERDA in the American Quarter Horse.
AB  - Hereditary equine regional dermal asthenia (HERDA), a degenerative skin disease
      that affects the Quarter Horse breed, was localized to ECA1 by homozygosity
      mapping. Comparative genomics allowed the development of equine gene-specific
      markers which were used with a set of affected horses to detect a homozygous,
      identical-by-descent block spanning approximately 2.5 Mb, suggesting a recent
      origin for the HERDA mutation. We report a mutation in cyclophilin B (PPIB) as a
      novel, causal candidate gene for HERDA. A c.115G>A missense mutation in PPIB
      alters a glycine residue that has been conserved across vertebrates. The mutation
      was homozygous in 64 affected horses and segregates concordant with inbreeding
      loops apparent in the genealogy of 11 affected horses. Screening of control
      Quarter Horses indicates a 3.5% carrier frequency. The development of a test that
      can detect affected horses prior to development of clinical signs and carriers of
      HERDA will allow Quarter Horse breeders to eliminate this debilitating disease.

PMID- 17498918
TI  - Gene identification and evidence for expression of G protein alpha subunits,
      phospholipase C, and an inositol 1,4,5-trisphosphate receptor in Aplysia
      californica rhinophore.
AB  - In the marine mollusk Aplysia californica, waterborne protein pheromones that are
      released during egg laying act in concert to stimulate mate attraction. However,
      molecular information concerning the cellular receptors and signaling mechanisms
      that may be involved in waterborne peptide and protein pheromonal communication
      is lacking. As a first step toward examining whether members of the G protein
      family and phosphoinositide signaling pathway are present in the primary
      peripheral chemosensory organs (i.e., rhinophores), we isolated five full-length
      cDNA clones from an A. californica central nervous system cDNA library. These
      clones encoded (1) the G protein alpha subunits of the Gq, Gi, and Go families,
      (2) a protein with homology to phospholipase C (PLC) isoforms, and (3) an
      inositol 1,4,5-trisphosphate receptor (IP3R). The expression of these genes was
      examined using laser capture microdissection/reverse transcription-polymerase
      chain reaction and in situ hybridization. All of them are expressed in the
      rhinophore sensory epithelium, suggesting that Galphaq, Galphai, Galphao, PLC
      like protein, and IP3R may be involved in waterborne protein pheromone detection
      in Aplysia-possibly via a phosphoinositide signaling mechanism.

PMID- 17498919
TI  - Distribution analysis of nonsynonymous polymorphisms within the human kinase gene
      family.
AB  - The human kinase gene family is composed of 518 genes that are involved in a
      diverse spectrum of physiological functions. They are also implicated in a number
      of diseases and encompass 10% of current drug targets. Contemporary, high
      throughput sequencing efforts have identified a rich source of naturally
      occurring single nucleotide polymorphisms (SNPs) in kinases, a subset of which
      occur in the coding region of genes (cSNPs) and result in a change in the encoded
      amino acid sequence (nonsynonymous coding SNP; nscSNPs). What fraction of this
      naturally occurring variation underlies human disease is largely unknown (uDC),
      and much of it is assumed not to be disease causing (DC). We pursued a
      comprehensive computational analysis of the distribution of 1463 nscSNPs and 999
      DC nscSNPs within the kinase gene family and have found that DCs are
      overrepresentated in the kinase catalytic domain and in receptor structures. In
      addition, the frequencies with which specific amino acid changes occur differ
      between the DCs and the uDCs, implying different biological characteristics for
      the two sets of human polymorphisms. Our results provide insights into the
      sequence and structural phenomena associated with naturally occurring kinase
      nscSNPs that contribute to human diseases.

PMID- 17498920
TI  - Characterization of Arabidopsis AtUGT85A and AtGUS gene families and their
      expression in rapidly dividing tissues.
AB  - In humans, uridine 5'-diphosphate glucuronosyltransferase (UGT) operates in
      opposition to glucuronidase (GUS) to control activity of diverse metabolites such
      as hormones by reversible conjugation with glucuronic acid. Previous data
      revealed that, as in mammals, these enzymes are required for plant life in that a
      UGT from Pisum sativum (PsUGT1) controls plant development by opposing endogenous
      GUS activity thereby modulating the duration of the cell cycle. Here we report
      that a small family of genes (AtUGT85A1, 2, 3, 4, 5, and 7) homologous to pea
      PsUGT1 exists in the Arabidopsis genome. The AtUGT85A-encoded proteins are
      predicted to be membrane-associated enzymes. Three genes (AtGUS1, AtGUS2, and
      AtGUS3) that are homologous to a GUS-encoding gene from Scutellaria baicalensis
      were identified. The AtGUS-encoded proteins are predicted to be secretory
      (AtGUS1) and membrane-associated (AtGUS2 and AtGUS3) enzymes. Both AtUGT85A and
      AtGUS genes, like PsUGT1, exhibit localized, tissue-specific expression, mainly
      in areas of active cell division with possible involvement in cell cycle
      regulation.

PMID- 17498922
TI  - Somatic instability of the expanded GAA triplet-repeat sequence in Friedreich
      ataxia progresses throughout life.
AB  - Friedreich ataxia (FRDA) patients are homozygous for expanded GAA triplet-repeat
      alleles in the FXN gene. Primary neurodegeneration involving the dorsal root
      ganglia (DRG) results in progressive ataxia. While it is known that DRG are
      inherently sensitive to frataxin deficiency, recent observations also indicate
      that they show age-dependent, further expansion of the GAA triplet-repeat
      mutation. Whether somatic instability is progressive has not been systematically
      investigated in FRDA patients. "Small-pool" PCR analysis of approximately 2300
      individual molecules from tissues of an 18-week fetus homozygous for expanded
      alleles revealed very low levels of instability compared with adult-derived
      tissues (4.2% versus 30.6%, p<0.0001). Mutation load in blood samples from
      multiple patients and carriers increased significantly with age, ranging from
      7.5% at 18-weeks gestation to 78.7% at 49 years of age (R=0.91; p=0.0001).
      Therefore, somatic instability in FRDA occurs mostly after early embryonic
      development and progresses throughout life, lending further support to the role
      of postnatal somatic instability in disease pathogenesis.

PMID- 17498923
TI  - Genomic survey of sequence features for ultraviolet tolerance in Haloarchaea
      (family Halobacteriaceae).
AB  - We have investigated the strategy of Halobacterium sp. NRC-1 and other members of
      the family Halobacteriaceae to survive ultraviolet (UV) irradiation, based on an
      integrated analysis of various genomic and proteomic features such as
      dinucleotide composition and distribution of tetranucleotides in the genome and
      amino acid composition of the proteins. The low dipyrimidine content may help
      Halobacterium reduce formation of photoproducts in its genome. The usage of
      residues susceptible to reactive oxygen species attack is reduced significantly
      in Halobacterium, which helps the organism to minimize protein damage. We then
      correlated the expression of the zim gene with the genomic structure to reexamine
      the importance of the putative mismatch repair pathway proposed previously. Our
      results showed that Halobacterium sp. NRC-1 and other haloarchaea (Haloarcula
      marismortui, Haloquadratum walsbyi) have optimized their genomic and proteomic
      structures to reduce damage induced by UV irradiation, often present at high
      levels in habitats where these organisms thrive.

PMID- 17498925
TI  - Dermoid cyst of the parotid gland--a case report and brief review of the
      literature.
AB  - There is controversy over the frequency of dermoid cysts in the head and neck
      area. Some authors report that they are common, whereas others say that only 7%
      of such cysts occur in the head and neck area. In either case, they are extremely
      rare in the parotid gland. When PubMed is searched for 'dermoid cyst of the
      parotid gland', only 11 articles are listed. Only four of the articles written in
      English are case reports of dermoid cysts of the parotid gland. Due to the rarity
      of descriptions and the considerable diversity of swellings of the parotid gland
      diagnosis is difficult. Visualizing options like computed tomography, magnetic
      resonance imaging and ultrasound cannot give a conclusive preoperative diagnosis.
      This case report shows the challenges in diagnosis and gives a short review of
      the literature.

PMID- 17498924
TI  - In search of polymorphic Alu insertions with restricted geographic distributions.
AB  - Alu elements are transposable elements that have reached over one million copies
      in the human genome. Some Alu elements inserted in the genome so recently that
      they are still polymorphic for insertion presence or absence in human
      populations. Recently, there has been an increasing interest in using Alu
      variation for studies of human population genetic structure and inference of
      individual geographic origin. Currently, this requires a high number of Alu loci.
      Here, we used a linker-mediated polymerase chain reaction method to
      preferentially identify low-frequency Alu elements in various human DNA samples
      with different geographic origins. The candidate Alu loci were subsequently
      genotyped in 18 worldwide human populations (approximately 370 individuals),
      resulting in the identification of two new Alu insertions restricted to
      populations of African ancestry. Our results suggest that it may ultimately
      become possible to correctly infer the geographic affiliation of unknown samples
      with high levels of confidence without having to genotype as many as 100 Alu
      loci. This is desirable if Alu insertion polymorphisms are to be used for human
      evolution studies or forensic applications.

PMID- 17498926
TI  - A haemangiopericytoma of the ethmoid sinus causing oncogenic osteomalacia: a case
      report and review of the literature.
AB  - Oncogenic osteomalacia is a rare cause of osteomalacia. It is caused by a tumour
      which is generally benign. These tumours, when identified, are often found in the
      head and neck region. The case is reported here of a haemangiopericytoma isolated
      in the ethmoid sinus, and the literature regarding tumours at this site is
      reviewed. Including the present case there are five reported in the world
      literature of an ethmoid sinus tumour causing oncogenic osteomalacia. The
      treatment for this disease is excision of the mass, which is where the head and
      neck specialist's expertise is required.

PMID- 17498927
TI  - Factor analytic support for social cognition as a separable cognitive domain in
      schizophrenia.
AB  - Social cognition has received increasing attention in schizophrenia due to its
      theoretical relevance to core features of the disorder as well as the marked
      deficits in social functioning exhibited by these patients. However, there
      remains a need to develop and validate measures of social cognitive abilities and
      to demonstrate that they are constructs that are separable from non-social
      neurocognitive processes. In the current study, the Wechsler Adult Intelligence
      Scale-Revised (WAIS-R) was administered to 169 males with schizophrenia, and test
      results were subjected to confirmatory factor analysis (CFA) to determine if
      those WAIS-R subtests containing social content would form a distinct Social
      Cognition (SC) factor. CFA was used to evaluate various models that hypothesized
      an SC factor, and for comparison purposes the same models were evaluated in the
      WAIS-R standardization sample. Results confirmed the presence of a four-factor
      model that included an SC factor, as well as the more commonly reported Verbal
      Comprehension, Perceptual Organization, and Working Memory factors. The SC factor
      consisted of the Picture Arrangement and Picture Completion subtests, and
      demonstrated small but significant correlations with disorganization and negative
      symptoms, as well as with an index of social functioning. Results provide support
      for the validity of the SC factor as a measure of social cognition in
      schizophrenia, and demonstrate that at least some aspects of social cognition
      represent separable cognitive domains in schizophrenia.

PMID- 17498921
TI  - Construction and application of EST library from Setaria italica in response to
      dehydration stress.
AB  - Foxtail millet is a gramineous crop with low water requirement. Despite its high
      water use efficiency, less attention has been paid to the molecular genetics of
      foxtail millet. This article reports the construction of subtracted cDNA
      libraries from foxtail millet seedlings under dehydration stress and the
      expression profile analysis of 1947 UniESTs from the subtracted cDNA libraries by
      a cDNA microarray. The results showed that 95 and 57 ESTs were upregulated by
      dehydration stress, respectively, in roots and shoots of seedlings and that 10
      and 27 ESTs were downregulated, respectively, in roots and shoots. The expression
      profile analysis showed that genes induced in foxtail millet roots were different
      from those in shoots during dehydration stress and that the early response to
      dehydration stress in foxtail millet roots was the activation of the glycolysis
      metabolism. Moreover, protein degradation pathway may also play a pivotal role in
      drought-tolerant responses of foxtail millet. Finally, Northern blot analysis
      validated well the cDNA microarray data.

PMID- 17498929
TI  - P300 asymmetry and positive symptom severity: a study in the early stage of a
      first episode of psychosis.
AB  - The amplitude of the P300 event-related potential (ERP) has been reported to be
      reduced over left compared to right temporal sites in schizophrenia patients.
      This left temporal P300 reduction has been associated with positive symptom
      severity and gray matter reduction in the left superior temporal gyrus. We
      investigated a group of patients with a first episode of schizophrenia spectrum
      psychosis and a group of normal controls to verify if P300 amplitude asymmetry
      already exists around the time of presentation for treatment. Relative to normal
      control subjects, no P300 asymmetry was found in patients. Nevertheless, P300
      asymmetry was correlated with the severity of positive symptoms and worse global
      functioning (GAF), a good predictor of poor outcome.

PMID- 17498928
TI  - Reduced N-acetyl-aspartate levels in schizophrenia patients with a younger onset
      age: a single-voxel 1H spectroscopy study.
AB  - Schizophrenia is widely considered a neurodevelopmental disorder. The timing of
      psychosis onset may determine the degree of functional and biological deficits.
      In this study, the association between age of onset of psychosis and in vivo
      biochemical levels was assessed in first-episode, antipsychotic-naive (FEAN)
      schizophrenia subjects. We hypothesized greater biochemical deficits in the
      younger-onset FEAN subjects. In vivo, (1)H spectroscopy measurements of the left
      dorsolateral prefrontal cortex (DLPFC) were conducted on FEAN subjects (15
      schizophrenia and 3 schizoaffective subjects) and healthy comparison subjects of
      comparable age and gender distribution (N=61). N-acetyl-aspartate was
      significantly lower in the left DLPFC of FEAN subjects as compared to healthy
      comparison subjects. However, there was a significant subject group-by-age
      interaction for N-acetyl-aspartate. Early-onset FEAN subjects showed lower N
      acetyl-aspartate levels compared to the younger healthy comparison subjects,
      while adult-onset FEAN and older healthy comparison subjects did not differ. The
      lower N-acetyl-aspartate levels in the DLPFC of early-onset subjects suggest a
      reduction in functioning neurons or specifically a reduction in the proliferation
      of dendrites and synaptic connections, which is not apparent in the adult-onset
      schizophrenia subjects.

PMID- 17498930
TI  - The study of the influence of surfactant charge on alkaline hydrolysis reactions
      of acetylsalicylic acid (ASA) and triflusal (TFL) using spectrophotometric
      methods.
AB  - In this research, the effects of micellar systems on alkaline hydrolysis
      reactions of acetylsalicylic acid (ASA) and triflusal (TFL) were found to be
      dependant upon the surfactant charge within the micelle. In cationic micelles,
      there is a catalytic effect at low concentrations of surfactant. However, this
      reaction is inhibited at higher surfactant concentrations. In anionic micelles, a
      catalytic effect occurs, while in zwitterionic and non-ionic micelles there is an
      inhibitory effect. Such reactions are attributable to changes in reactants on the
      micellar surface, or to the fact that both reactants are found in different
      microenvironments. The pseudophase (PS) and ion-exchange (PPIE) models were found
      to be consistent with the experimental result. Furthermore, the association
      constants for both drugs could be determined together with micellar rate
      constants in heterogeneous media.

PMID- 17498931
TI  - [Steroid therapy for hydrocephalus due to acute cerebellitis in a child].
AB  - Severe acute inflammatory cerebellitis is a rare but life threatening disease. We
      report the case of a 8-year-old boy presenting with cerebellitis and acute
      cerebellar swelling complicated by brain stem compression and hydrocephalus.
      Outcome was good on steroid therapy.

PMID- 17498932
TI  - Is there a plastid in Perkinsus atlanticus (Phylum Perkinsozoa)?
AB  - Perkinsus atlanticus is a pathogenic protist that infects the clam Ruditapes
      decussatus. The recent proposal for the inclusion of the genus Perkinsus in a new
      phylum, Perkinsozoa, in the infra-kingdom Alveolata, gave rise to controversies
      whether this genus should form a phylum on its own. Molecular analysis of some
      conserved nuclear genes shows a closer proximity of the genus Perkinsus to the
      dinoflagellates than to the apicomplexans. Studies on extranuclear genomes,
      however, could also be very helpful for a more precise definition of those phyla.
      In Perkinsozoa, there have been until now no reports about the isolation of
      mitochondria as well as no conclusive results about the presence of any plastids,
      therefore a comparison with the data already obtained in Apicomplexa and
      Dinoflagellata has not yet been possible. In this work, we identify a plastid in
      Perkinsus atlanticus, using ultrastructural techniques and inhibition growth
      tests. It will be important to analyze the plastid genome at a molecular level,
      in order to confirm if the plastid in Perkinsus is more similar to those of
      Dinoflagellata or Apicomplexa. Such information will doubtless contribute to a
      more precise determination of the phylogenetic position of the genus Perkinsus.

PMID- 17498933
TI  - Infection of algae-free Climacostomum virens with symbiotic Chlorella sp.
      isolated from algae-containing C. virens.
AB  - The ciliate Climacostomum virens normally contains algae as symbionts in its
      cytoplasm and retains them over many generations. An aposymbiotic strain of C.
      virens which cannot re-establish a new symbiotic association by ingestion of
      algae derived from green Climacostomum was recently isolated in our laboratory.
      Results of infection experiments showed that all newly ingested, potentially
      symbiotic algae were digested in food vacuoles. To clarify whether these ciliates
      have completely lost their ability to sustain symbiosis with algae or whether
      this ability can eventually be re-established, infection experiments were
      performed using a microinjection technique. We have achieved successful infection
      of algae-free Climacostomum using this method. The endosymbiont population was
      established in ciliates from as few as 3-5 injected algae, which have retained an
      intact perialgal vacuole membrane around them. To our knowledge, this is the
      first evidence of successful infection of aposymbiotic ciliates with algae by
      microinjection.

PMID- 17498934
TI  - In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet
      formulations: a pharmacoscintigraphic study in the beagle dog.
AB  - The aim of the current study was to investigate the in-vitro and in-vivo
      performance of a press-coated tablet (PCT) intended for time delayed drug
      release, consisting of a rapidly disintegrating theophylline core tablet, press
      coated with barrier granules containing glyceryl behenate (GB) and low
      substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release
      with a lag time dependent upon the GB and L-HPC composition of the barrier layer.
      In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC
      at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either
      the fed or fasted state. The in-vivo lag time in both the fed and fasted states
      did not differ significantly (p>0.05) from the in-vitro lag time. Additionally,
      no significant difference (p<0.05) between in-vivo fed and fasted disintegration
      times was observed, demonstrating that in-vivo performance of the PCT was not
      influenced by the presence or absence of food in the gastrointestinal tract. A
      distinct lag time was obtained prior to the appearance of drug in plasma and
      correlated (R2=0.98) with disintegration time observed from scintigraphic images.
      However, following disintegration, no difference in pharmacokinetic parameters
      (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the
      potential use of these formulations for chronopharmaceutical drug delivery.

PMID- 17498935
TI  - Vitamin-loaded electrospun cellulose acetate nanofiber mats as transdermal and
      dermal therapeutic agents of vitamin A acid and vitamin E.
AB  - The present contribution reports the use of mats of electrospun cellulose acetate
      (CA; acetyl content=39.8%; Mw=30,000 Da) nanofibers as carriers for delivery of
      the model vitamins, all-trans retinoic acid or vitamin A acid (Retin-A) and alpha
      tocopherol or vitamin E (Vit-E). The amounts of Vit-E and Retin-A loaded in the
      base CA solution [17% w/v in 2:1 v/v acetone/N,N-dimethylacetamide (DMAc)] were 5
      and 0.5 wt% (based on the weight of CA), respectively. Cross-sectionally round
      and smooth fibers were obtained. The average diameters of these fibers ranged
      between 247 and 265 nm. The total immersion of the vitamin-loaded as-spun CA
      fiber mats in the acetate buffer solutions containing either 0.5 vol % Tween 80
      or 0.5 vol % Tween 80 and 10 vol % methanol was used to arrive at the cumulative
      release of the vitamins from the fiber mat samples. The same was also conducted
      on the vitamin-loaded solution-cast CA films for comparison. In most cases, the
      vitamin-loaded as-spun fiber mats exhibited a gradual and monotonous increase in
      the cumulative release of the vitamins over the test periods (i.e., 24 h for Vit
      E-loaded samples and 6 h for Retin-A-loaded ones), while the corresponding as
      cast films exhibited a burst release of the vitamins.

PMID- 17498936
TI  - Methionine-supplemented diet augments hepatotoxicity and prooxidant status in
      chronically ethanol-treated rats.
AB  - The purpose of this study was to investigate whether high methionine (HM) diet
      may influence the development of ethanol-induced hepatotoxicity and prooxidant
      antioxidant balance in the liver. Rats received drinking water containing ethanol
      (20% v/v) and/or methionine supplemented diet (2% w/w) for 75 days. Although
      prooxidant-antioxidant balance did not change in the liver of rats in HM group,
      ethanol treatment was observed to increase plasma transaminase activities, and
      malondialdehyde (MDA) and protein carbonyl (PC) levels, but not glutathione
      (GSH), vitamin E and vitamin C levels, and superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in
      the liver of rats as compared to controls. However, ethanol plus HM diet caused
      further increases in plasma transaminase activities and hepatic MDA and PC
      levels. In addition, SOD, GSH-Px and GST activities were observed to decrease,
      but GSH, vitamin E and vitamin C levels remained unchanged in the liver as
      compared to ethanol, HM and control groups. Our results show that HM diet may
      augment hepatotoxicity and oxidative stress in the liver of chronically ethanol
      treated rats.

PMID- 17498938
TI  - Screening and distributing features of bacteria with hydantoinase and
      carbamoylase.
AB  - Hydantoinase and carbamoylase are key biocatalysts for the production of
      optically pure amino acids from dl-5-substituted hydantoins (SSH). Out of 364
      isolated strains with hydantoinase and carbamoylase at 45 degrees C, 24 strains
      showed efficient hydantoinase and carbamoylase activities. Among them, 17
      produced l-amino acids, and 7 produced d-amino acids from both aromatic dl-5
      benzylhydantoin and aliphatic dl-5-isopropylhydantoin. Most of the strains that
      were able to form l-amino acid belonged to genera Bacillus, Geobacillus,
      Brevibacillus, Aneurinibacillus, Microbacterium, and Kurthia. Phylogenetic
      relationships were investigated based on 16S rRNA from the hydantoinase-producing
      bacteria. Distinct tendencies toward certain genera were observed between most of
      the strains forming l-amino acids and d-amino acids from SSH. The results from
      this study can be utilized to develop new isolation technology of hydantoinase
      producing microorganisms, and to understand metabolism and evolutionary origins
      of hydantoinase and carbamoylase among different bacteria.

PMID- 17498939
TI  - Anti-atherogenic effects of seabuckthorn (Hippophaea rhamnoides) seed oil.
AB  - Seabuckthorn (SBT) seed oil is a rich source of unsaturated fatty acids,
      phytosterols, carotenoids and flavonoids, which are known to have significant
      anti-atherogenic and cardioprotective activity. The anti-atherogenic activity of
      supercritical CO(2) extracted SBT seed oil was evaluated in white albino rabbits
      fed on high cholesterol diet for 60 days. The study was performed on 20 male
      healthy rabbits divided into four groups of 5 animals each. Group I - control,
      group II - SBT seed oil, group III - cholesterol (1%) for 60 days, group IV -
      cholesterol+SBT seed oil. After 30 days of high cholesterol diet, group IV
      rabbits received 1 ml of SBT seed oil daily for 30 days. Blood total cholesterol
      (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and triglyceride (TG)
      levels were measured before and after the administration of SBT seed oil. The
      vasorelaxant activity of the seed oil was studied in vitro using aortic ring
      model technique and changes in isometric force were recorded using a polygraphic
      recording system. Accumulation of cholesterol in the aorta was studied using
      Sudan-IV staining technique. SBT seed oil feeding to normal rabbits for 18 days
      caused a significant decline in plasma cholesterol, LDL-C, atherogenic index (AI)
      and LDL/HDL ratio. The HDL-C levels, HDL-C/TC ratio (HTR) and vasorelaxant
      activity of the aorta were significantly increased. In cholesterol-fed animals
      the TC, TG, LDL-C and AI were significantly increased and showed a decline
      following seed oil administration. The increase in HDL-C was more marked in seed
      oil treated hypercholesterolemic animals. The acetylcholine-induced vasorelaxant
      activity was significantly decreased in cholesterol-fed animals and could be
      restored to that of normal values by seed oil administration. These observations
      suggest that supercritical CO(2) extracted SBT seed oil has significant anti
      atherogenic and cardioprotective activity.

PMID- 17498940
TI  - Antidepressant-like effect of Cecropia glazioui Sneth and its constituents - in
      vivo and in vitro characterization of the underlying mechanism.
AB  - The present study aimed to characterize the antidepressant-like effect of a
      standardized aqueous extract (AE) of Cecropia glazioui Sneth and its purified
      fractions on in vivo (forced swimming test), ex vivo (hippocampal monoamines
      levels) and in vitro (serotonin, noradrenaline and dopamine uptake) tests,
      searching for the active principles and the underlying mechanisms of action.
      Treatment with AE, or with its butanolic fraction (BuF), the latter rich in
      catechins, procyanidins and flavonoids, reduced the immobility of rats in the
      forced swimming test indicating an antidepressant-like effect. Biochemical
      analysis of the hippocampal neurotransmitters in BuF-treated rats showed
      significant increase in monoamines levels. BuF and six of its purified
      constituents inhibited the uptake of [(3)H]-serotonin, [(3)H]-dopamine and [(3)H]
      noradrenaline by synaptosomes of different brain regions. Catechin, catechin
      (4alpha-->8) ent-catechin (Procyanidin B3 isomer) and epicatechin (4beta-->8)
      epicatechin (Procyanidin B2) were the most active compounds. Comparatively, the
      uptake of [(3)H]-noradrenaline was the most affected. These results show that the
      antidepressant-like effect promoted by C. glazioui extract is most likely due to
      the blockade of the monoamines uptake in the CNS.

PMID- 17498941
TI  - Acute toxicity of Orthosiphon stamineus Benth standardized extract in Sprague
      Dawley rats.
AB  - The acute toxicity of standardized extract of Orthosiphon stamineus was studied
      in Sprague Dawley rats. The rats were administered a single dose of 5000 mg/kg
      body weight (BW) orally on Day 0 and observed for 14 days. There were no deaths
      recorded and the animals did not show signs of toxicity during the experimental
      period. The effect of the extract on general behavior, BW, food and water intake,
      relative organ weight per 100 g BW, hematology and clinical biochemistry were
      measured. All the parameters measured were unaffected as compared to the control.
      The acute toxicity LD(50) was estimated to be > 5000 mg/kg BW.

PMID- 17498942
TI  - Inhibitory effect of rhetsinine isolated from Evodia rutaecarpa on aldose
      reductase activity.
AB  - Aldose reductase inhibitors have considerable potential for the treatment of
      diabetic complications, without increased risk of hypoglycemia. Search for
      components inhibiting aldose reductase led to the discovery of active compounds
      contained in Evodia rutaecarpa Bentham (Rutaceae), which is the one of the
      component of Kampo-herbal medicine. The hot water extract from the E. rutaecarpa
      was subjected to distribution or gel filtration chromatography to give an active
      compound, N2-(2-methylaminobenzoyl)tetrahydro-1H-pyrido[3,4-b]indol-1-one
      (rhetsinine). It inhibited aldose reductase with IC(50) values of 24.1 microM.
      Furthermore, rhetsinine inhibited sorbitol accumulation by 79.3% at 100 microM.
      These results suggested that the E. rutaecarpa derived component, rhetsinine,
      would be potentially useful in the treatment of diabetic complications.

PMID- 17498943
TI  - Do thin spines learn to be mushroom spines that remember?
AB  - Dendritic spines are the primary site of excitatory input on most principal
      neurons. Long-lasting changes in synaptic activity are accompanied by alterations
      in spine shape, size and number. The responsiveness of thin spines to increases
      and decreases in synaptic activity has led to the suggestion that they are
      'learning spines', whereas the stability of mushroom spines suggests that they
      are 'memory spines'. Synaptic enhancement leads to an enlargement of thin spines
      into mushroom spines and the mobilization of subcellular resources to potentiated
      synapses. Thin spines also concentrate biochemical signals such as Ca(2+),
      providing the synaptic specificity required for learning. Determining the
      mechanisms that regulate spine morphology is essential for understanding the
      cellular changes that underlie learning and memory.

PMID- 17498944
TI  - Functional analysis of cholesterol biosynthesis by RNA interference.
AB  - Inborn errors of cholesterol biosynthesis caused by dysfunctionality of single
      enzymes are known to cause severe malformation syndromes like X-linked
      chondrodysplasia punctata (CDPX2), CHILD syndrome or Smith-Lemli-Opitz-syndrome
      (SLOS). In this study we established the method of RNA interference (RNAi) for
      analyzing the molecular mechanisms underlying disrupted cholesterol biosynthesis.
      For different genes involved in the cholesterol biosynthesis pathway-NAD(P)
      dependent steroid dehydrogenase-like (NSDHL), 17-beta hydroxysteroid
      dehydrogenase type 7 (HSD17B7) and emopamil binding protein (EBP)-shRNA sequences
      were designed and tested for their effectiveness. For a better comparability of
      the experiments and to avoid different transfection efficiencies, examined shRNA
      sequences which reached a knock down of at least 80% were stably transfected in a
      HeLa cell line with a tetracycline-regulated expression (HeLa T-REx). These
      stable transfected cell lines represent novel tools for the analysis of
      cholesterol biosynthesis.

PMID- 17498946
TI  - Inactivation of Cryptosporidium parvum oocysts in water using ultrasonic
      treatment.
AB  - Ultrasound in a liquid phase cause mass and heat transfer across the liquid
      through cavitational processes which act as nanoreactors to generate unstable
      mechanical equilibrium. The effect of 1 MHz ultrasound on the inactivation of
      Cryptosporidium parvum was investigated. Continuous irradiation of ultrasound (20
      min) increased temperature due to cavitational phenomena. Ultrasound irradiation
      of liquid containing C. parvum showed significant quantitative changes in pH,
      temperature and inactivation of C. parvum (102.7 oocysts killed/s) with a minimum
      energy consumption (0.05 oocysts/s).

PMID- 17498947
TI  - Conversion of olive tree biomass into fermentable sugars by dilute acid
      pretreatment and enzymatic saccharification.
AB  - The production of fermentable sugars from olive tree biomass was studied by
      dilute acid pretreatment and further saccharification of the pretreated solid
      residues. Pretreatment was performed at 0.2%, 0.6%, 1.0% and 1.4% (w/w) sulphuric
      acid concentrations while temperature was in the range 170-210 degrees C.
      Attention is paid to sugar recovery both in the liquid fraction issued from
      pretreatment (prehydrolysate) and that in the water-insoluble solid (WIS). As a
      maximum, 83% of hemicellulosic sugars in the raw material were recovered in the
      prehydrolysate obtained at 170 degrees C, 1% sulphuric acid concentration, but
      the enzyme accessibility of the corresponding pretreated solid was not very high.
      In turn, the maximum enzymatic hydrolysis yield (76.5%) was attained from a
      pretreated solid (at 210 degrees C, 1.4% acid concentration) in which cellulose
      solubilization was detected; moreover, sugar recovery in the prehydrolysate was
      the poorest one among all the experiments performed. To take account of
      fermentable sugars generated by pretreatment and the glucose released by
      enzymatic hydrolysis, an overall sugar yield was calculated. The maximum value
      (36.3 g sugar/100 g raw material) was obtained when pretreating olive tree
      biomass at 180 degrees C and 1% sulphuric acid concentration, representing 75% of
      all sugars in the raw material. Dilute acid pretreatment improves results
      compared to water pretreatment.

PMID- 17498948
TI  - Cyclic benzamidines as orally efficacious NR2B-selective NMDA receptor
      antagonists.
AB  - A novel series of cyclic benzamidines was synthesized and shown to exhibit NR2B
      subtype selective NMDA antagonist activity. Compound 29 is orally active in a
      carrageenan-induced rat hyperalgesia model of pain.

PMID- 17498949
TI  - Liver X receptor antagonists with a phthalimide skeleton derived from thalidomide
      related glucosidase inhibitors.
AB  - Alpha-glucosidase inhibitors with a chlorinated phthalimide or a thiophthalimide
      skeleton, derived from thalidomide, were found to possess liver X receptor (LXR)
      antagonistic activity. Novel LXR antagonists with a 2'-substituted
      phenylphthalimide skeleton were obtained by structural development of glucosidase
      inhibitors derived from thalidomide.

PMID- 17498950
TI  - Discovery of highly potent and selective benzyloxybenzyl-based peroxisome
      proliferator-activator receptor (PPAR) delta agonists.
AB  - A series of 1,4-benzyloxybenzylsulfanylaryl carboxylic acids were prepared and
      their activities for PPAR receptor subtypes (alpha, delta, and gamma) with
      potential indications for the treatment of dyslipidemia were investigated. Analog
      13a displayed the greatest binding affinity (IC(50)=10nM) and selectivity (120
      fold) for PPARdelta over PPARalpha. Many of the analogs investigated were found
      to be highly selective for PPARdelta and were dependent on the point of
      attachment of the substituent. In the 1,4-series, analog 28e was found to be the
      most potent (IC(50)=1.7 nM) and selective (>1000-fold) compound for PPARdelta.
      None of the compounds tested showed appreciable binding affinity for PPARgamma.

PMID- 17498951
TI  - Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the
      development of antitumor agents as topoisomerase I inhibitors.
AB  - An intramolecular radical cyclization reaction of 4-bromo-3-arylisoquinolines 11a
      c allowed the efficient synthesis of 11-methylindenoisoquinolines 2a-c. 5-(2
      Aminoethylamino)indeno[1,2-c]isoquinolin-11-one 4 was also prepared in the
      convenient manner. The synthesized compounds were tested in vitro for
      cytotoxicity and DNA-topoisomerase 1 (top 1) inhibitory activity. The dramatic
      enhancement of top 1 inhibitory activity of 4 was explained by a docking study
      using the FlexX program.

PMID- 17498952
TI  - The discovery of long acting beta2-adrenoreceptor agonists.
AB  - The design and profile of a series of saligenin containing long acting beta(2)
      adrenoreceptor agonists is described. Evaluation of these analogues using a
      guinea-pig tissue model demonstrates that analogues within this series have
      significantly longer durations of action than salmeterol and have the potential
      for a once daily profile in human.

PMID- 17498953
TI  - A new class of histamine H3 receptor antagonists derived from ligand based
      design.
AB  - Design and synthesis of highly potent and selective non-imidazole inverse
      agonists for the histamine H(3) receptor is described. The study validates a new
      pharmacophore model based on the merging of two previously described models. It
      also demonstrates that the removal of the basic center potentially interacting
      with ASP3.32 and common to both models leads to loss of activity, whereas the
      replacement of the second basic center by an acceptor retains the potency.

PMID- 17498954
TI  - Synthesis and SAR of thiophene containing kinesin spindle protein (KSP)
      inhibitors.
AB  - We have identified and synthesized a series of thiophene containing inhibitors of
      kinesin spindle protein. SAR studies led to the synthesis of 33, which was co
      crystallized with KSP and determined to bind to an allosteric pocket previously
      described for other known KSP inhibitors.

PMID- 17498955
TI  - Large-scale biophysics: ion flows and regeneration.
AB  - Regeneration requires exquisite orchestration of growth and morphogenesis. A
      powerful but still largely mysterious system of biophysical signals functions
      during regeneration, embryonic development and neoplasm. Ion transporters
      generate pH and voltage gradients, as well as ion fluxes, regulating
      proliferation, differentiation and migration. Endogenous bioelectrical signals
      are implicated in the control of wound healing, limb development, left-right
      patterning and spinal cord regeneration. Recent advances in molecular biology and
      imaging technology have allowed unprecedented insight into the sources and
      downstream consequences of ion flows. In complement to the current focus on
      molecular genetics and stem cell biology, artificial modulation of bioelectrical
      signals in somatic tissues is a powerful modality that might result in profound
      advances in understanding and augmentation of regenerative capacity.

PMID- 17498956
TI  - The peripheral nervous system and the perception of verticality.
AB  - Orientation of the body with respect to gravity is based on integration of
      visual, vestibular and somatosensory signals. Here, we investigated the
      subjective postural vertical (SPV) and visual vertical (SVV) in three patients
      with bilateral somatosensory deafferentation and a group of age-matched normal
      subjects. Our hypothesis was that the patients with bilateral somatosensory
      deafferentation may show tilt induced bias in the construction of their SPV, with
      a normal SVV. Patient 1 had a severe Guillain Barre syndrome and almost complete
      absence of peripheral sensation, the two other patients had a thoracic spinal
      injury with a sensory loss from T6-7 down. On initial testing, compared with
      normal subjects and the patients with spinal injury, Patient 1 had a significant
      bias in SPV towards the side of a preceding tilt in both directions. Several
      months later, after significant improvement of sensation, this tilt-induced bias
      in SPV had resolved completely. In addition, Patient 1 had a significantly
      enlarged "cone of verticality", which did not change following improvement in
      peripheral sensation, reflecting persisting disturbance in the perception of body
      verticality. In the two patients with spinal injury, bias towards the side of a
      preceding tilt was not significant. These findings confirm the importance of
      somatosensory input from the trunk to the perception of SPV in the seated
      position.

PMID- 17498957
TI  - Decapitation: poxvirus makes RNA lose its head.
AB  - Cellular infection by vaccinia virus involves the controlled degradation of
      early, intermediate and late viral mRNAs, and increased turnover of host mRNAs. A
      new study has identified a key mediator of both these processes. A Nudix
      hydrolase encoded by the viral D10 gene decaps these mRNAs, thus targeting them
      for destruction independently of cellular systems. This finding has several
      implications for virus evolution and the regulation of RNA decapping.

PMID- 17498958
TI  - Caco-2 cell permeability and stability of two d-glucopyranuronamide conjugates of
      thyrotropin-releasing hormone.
AB  - Caco-2 cell permeability and stability assays were used as an in vitro model to
      study the intestinal epithelial transport and stability of two analogues of
      thyrotropin-releasing hormone (TRH; Pyr-His-Pro-NH2). Peptide 1 (Pyr-His-Pro-D
      glucopyranuronamide) was more permeable across the Caco-2 cell monolayer compared
      with the permeability of the parent TRH peptide (Papp=5.10+/-1.89x10(-6) cm/s
      c.f. Papp=0.147+/-0.0474x10(-6) cm/s respectively). The permeability of peptide 1
      was improved threefold by attaching a 2-aminooctanoic acid moiety to the N
      terminus to form peptide 2 (2-aminooctanoic acid-Gln-His-Pro-D
      glucopyranuronamide) (Papp=16.3+/-2.47x10(-6) cm/s). The half-life for both
      peptide 1 and peptide 2 was approximately 20 min in a homogenate of Caco-2 cells
      compared with the half-life of TRH which is approximately 3 min. It was concluded
      that the permeability of peptides 1 and 2 was enhanced because of their increased
      stability, while the higher permeability of peptide 2 compared with peptide 1 may
      be attributed to its increased lipophilicity which results in enhanced passive
      diffusion.

PMID- 17498959
TI  - Sulfated glucosamine inhibits MMP-2 and MMP-9 expressions in human fibrosarcoma
      cells.
AB  - In the present study, sulfated glucosamine (SGlc) that has been reported to
      relieve joint pain and inflammation in many arthritis patients was studied for
      its inhibitory effects on MMP-2 and MMP-9 in human fibrosarcoma cells. Expression
      and activity of above MMPs studied using gelatin zymography suggested SGlc as a
      potent MMP inhibitor. Further, transfection of promoter genes of MMPs and their
      transcription factors clearly exhibited that inhibition of MMP-2 and MMP-9 was
      due to down-regulation of transcription factor, NF-kappaB. However expression of
      activator protein-1 (AP-1), another important transcription factor of MMPs, was
      not affected by SGlc treatment. In addition, protein expression results of
      Western blot analysis were also in agreement with the results of gene
      transfection experiments. Moreover, down-regulation of NF-kappaB resulted in
      production of low levels of both NF-kappaB p50 and p65 proteins and directly
      affected activation process of MMP-2 and MMP-9 expressions. Since MMPs involve in
      joint inflammation, it can be presumed that inhibition of MMP-2 and MMP-9 can be
      one of the mechanisms of SGlc to be an effective drug in relieving the symptoms
      of osteoarthritis.

PMID- 17498960
TI  - Alkylation potency and protein specificity of aromatic urea derivatives and
      bioisosteres as potential irreversible antagonists of the colchicine-binding
      site.
AB  - A number of N-phenyl-N'-(2-chloroethyl)ureas (CEUs) have been shown to be potent
      antimitotics through their covalent binding to the colchicine-binding site on
      intracellular beta-tubulin. The present communication aimed to evaluate the role
      of the electrophilic 2-chloroethyl amino moiety of CEU on cell growth inhibition
      and the specificity of the drugs as irreversible antagonists of the colchicine
      binding site. To that end, several N-phenyl-N'-(2-ethyl)urea (EU), N-phenyl-N'-(2
      chloroethyl)urea (CEU), N-aryl amino-2-oxazoline (OXA), and N-phenyl-N'-(2
      chloroacetyl)urea (CAU) derivatives were prepared and tested for their
      antiproliferative activity, their effect on the cell cycle, and their
      irreversible binding to beta-tubulin. EU derivatives were devoid of
      antiproliferative activity. CEUs (2h-2i, 2k, 2l, OXA 3e, 3h, 3i, 3k, 3l, tBCEU,
      and ICEU), OXA (3h, 3i, 3k, 3l, tBOXA, and IOXA), and CAU (4a-4m, tBCAU, and
      ICAU) had GI(50) between 1.7 and 10microM on three tumor cell lines. Cytotoxic
      CEU and OXA arrested the cell cycle in G(2)/M phase, while the corresponding CAU
      were not phase specific. Finally, Western blot analysis clearly showed that only
      CEUs 2h, 2k, 2l, tBCEU, ICEU and OXA 3h, 3i, 3k, 3l, tBOXA ,and IOXA were able to
      bind irreversibly to the colchicine-binding site. Our results suggest that
      increasing the potency of the electrophilic moiety of the aromatic ureas enhances
      their antiproliferative activity but decreases significantly their capacity to
      covalently bind to the colchicine-binding site.

PMID- 17498961
TI  - Synthesis and evaluation of new arylbenzo[b]thiophene and diarylthiophene
      derivatives as inhibitors of the NorA multidrug transporter of Staphylococcus
      aureus.
AB  - The synthesis based on palladium catalytic coupling of 38 new-arylated
      benzo[b]thiophenes or thiophenes is described in a few steps. We also report the
      direct arylation of the position 3 of the benzo[b]thiophenic structure, a 'one
      pot' 2,5-heterodiarylation of thiophenes as well as the synthesis of precursors
      of amino-acids with a 2-arylated benzo[b]thiophene core. These compounds were
      evaluated on bacteria strains: most of them did not exhibit any antibiotic
      activity but were found to selectively inhibit the NorA multidrug transporter of
      Staphylococcus aureus. As such, they restored the activity of the NorA substrates
      ciprofloxacin against a resistant S. aureus strain in which this efflux pump is
      over-expressed.

PMID- 17498962
TI  - Synthesis of analogues of a flexible thiopyrylium photosensitizer for purging
      blood-borne pathogens and binding mode and affinity studies of their complexes
      with DNA.
AB  - A series of thio- and selenopyrylium analogues of 2,4-di(4-dimethylaminophen-yl)
      6-methylthiopyrylium iodide were prepared in five steps from 4
      dimethylaminophenyl-propargyl aldehyde and the corresponding lithium acetylide.
      When bound to DNA, all of the dyes absorb at wavelengths >600nm, which avoids the
      hemoglobin band I maximum at 575nm. The binding of the series of dyes to double
      stranded DNA was examined spectrophotometrically and by isothermal titration
      calorimetry to determine binding constants, by a topoisomerase I DNA unwinding
      assay, by competition dialysis with [poly(dGdC)](2) and [poly(dAdT)](2), and by
      ethidium bromide displacement studies to examine propensities for intercalation,
      and by circular dichroism studies. The dyes were found to show mixed binding
      modes.

PMID- 17498963
TI  - Nano-structured biogenic calcite: a thermal and chemical approach to folia in
      oyster shell.
AB  - The thin sheets of calcite in oyster shell in Crassostrea gigas are termed folia
      and comprise much of the oyster shell. The folia are covered by a layer of
      discrete globules that has been proposed to consist of aggregations of an organic
      matrix and minerals. A continuous organic framework divides each tablet into
      nanograins. Their shape is globular with a mean extension from 30 to 40 nm.
      Chemical and thermal treatments to correlate between the organic matrix and the
      minerals are considered using spectrometers, thermal analyzers, and electron
      microscopes. After treatment, the nanograins of the foliar and organic matrix are
      clearly identified. The organic matrix plays a key role in the thermal stability
      and material properties of this biological composite. From analysis of the FT-IR
      results, it is identified that the organic matrix in folia is composed of
      proteins and polysaccharides.

PMID- 17498964
TI  - Visualization of neutrophil extracellular traps in TEM.
AB  - Neutrophil extracellular traps (NETs) have recently been described as an
      important innate defence mechanism in inflammation. However, routine electron
      microscopic staining techniques faintly stain NETs and are therefore insufficient
      for enabling a distinction between these and the host cell debris as well as
      proteins regularly present at the site of inflammation. In order to test suitable
      electron microscopic staining techniques, NETs induced ex vivo via phorbol
      myristate were absorbed on formvar. Four types of drop-on-grid positive staining
      were used: osmium tetroxide (Os), osmium tetroxide-uranyl acetate-lead citrate
      (Os-U-Pb), ruthenium red-osmium tetroxide (RR-OsO4), and cuprolinic blue enhanced
      by sodium tungstate (CB-WO4). We observed no staining of NETs using Os, faint
      staining with Os-U-Pb, better but still weak staining with CB-WO4 and outstanding
      staining with RR-OsO4. Furthermore, RR-OsO4 staining also enables the observation
      of bacterial fimbriae-mediated adhesion, which is possibly responsible for the
      ability of NETs to bind bacteria. Thus, the offered RR-OsO4 staining technique
      may facilitate the study of the NETs-bacterial interactions.

PMID- 17498965
TI  - The preventative role of growth hormone on acute liver injury induced by
      cardiopulmonary bypass in a rat model.
AB  - OBJECTIVE: Cardiopulmonary bypass (CPB)-induced acute liver injury is a life
      threatening complication after cardiac surgery and is thought to be associated
      with inflammatory response and acute-phase response (APR). Recombinant human
      growth hormone (rhGH) can modulate the APR and inflammatory response. Here, we
      tested the protective effect of GH on CPB-induced liver injury in the rat.
      METHODS: Adult male Sprague-Dawley rats (group G, received 2.5 mg/kg of rhGH
      intramuscularly at 8a.m. every 24h for 3 days and just before the initiation of
      CPB; group C served as control) underwent CPB (120 min, 120 ml/kg per minute, 34
      degrees C) and were killed 3h after the termination of CPB. RESULTS:
      Administration of rhGH markedly increased serum insulin-like growth factor (IGF)
      I and IGF-I-binding protein (IGFBP)-3 compared with group C. Group G showed
      significantly lower serum concentrations of alanine aminotransferase and total
      bilirubin after CPB termination. Those receiving rhGH demonstrated a significant
      increase in serum prealbumin and serum transferrin and a marked decrease in serum
      amyloid A and serum C-reactive protein compared with group C. rhGH significantly
      decreased serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta), whereas no changes were found for serum IL-6 and IL-10 compared with
      group C. rhGH significantly increased total liver protein content, hepatocyte
      proliferation, and decreased hepatocyte apoptosis versus group C. CONCLUSIONS:
      These results suggest that GH administration in rats seems to play a preventative
      role in acute liver injury associated with CPB via the decrease in acute-phase
      proteins, proinflammatory cytokines TNF-alpha and IL-1beta, and hepatocyte
      apoptosis, which is associated with increase in constitutive hepatic proteins,
      total liver protein content, and hepatocyte proliferation.

PMID- 17498966
TI  - Genetic susceptibility for breast cancer: how many more genes to be found?
AB  - Today, breast cancer is the most commonly occurring cancer among women. It
      accounts for 22% of all female cancers and the estimated annual incidence of
      breast cancer worldwide is about one million cases. Many risk factors have been
      identified but a positive family history remains among the most important ones
      established for breast cancer, with first-degree relatives of patients having an
      approximately two-fold elevated risk. It is currently estimated that
      approximately 20-25% of this risk is explained by known breast cancer
      susceptibility genes, mostly those conferring high risks, such as BRCA1 and
      BRCA2. However, these genes explain less than 5% of the total breast cancer
      incidence, even though several studies have suggested that the proportion of
      breast cancer that can be attributed to a genetic factor may be as high as 30%.
      It is thus likely that there are still breast cancer susceptibility genes to be
      found. It is presently not known how many such genes there still are, nor how
      many will fall into the class of rare high-risk (e.g. BRCAx) or of common low
      risk susceptibility genes, nor if and how these factors interact with each other
      to cause susceptibility (a polygenic model). In this review we will address this
      question and discuss the different undertaken approaches used in identifying new
      breast cancer susceptibility genes, such as (genome-wide) linkage analysis, CGH,
      LOH, association studies and global gene expression analysis.

PMID- 17498967
TI  - Association of IL-8-251A/T polymorphism with incidence of Acute Respiratory
      Distress Syndrome (ARDS) and IL-8 synthesis after multiple trauma.
AB  - INTRODUCTION: Interleukin-8 (IL-8) is regarded as one of the most important
      mediators in the pathogenesis of Adult Respiratory Distress Syndrome (ARDS).
      However, knowledge regarding the influence of genetic variations within the IL-8
      gene either on the development of ARDS or on IL-8 production in the traumatic
      setting is sparse. PATIENTS AND METHODS: In this prospective cohort study,
      patients were included if the following criteria were fulfilled: Injury Severity
      Score (ISS) >16, age 18-60 years and a survival >48 h after injury. Systemic IL-8
      concentrations and the polymorphisms (IL-8-251A/T) were determined. Patients were
      separated according to the development of ARDS (group +ARDS vs. group -ARDS) and
      the genotypes of the IL-8-251A/T polymorphism (genotypes A/A, A/T and T/T).
      RESULTS: Group +ARDS demonstrated significantly higher IL-8 plasma concentrations
      from day 3 until the end of the observation period compared to group -ARDS. In
      addition, duration of mechanical ventilation and length of stay in the ICU were
      significantly longer in this group. Furthermore, a significant association
      between the IL-8-251A allele and IL-8 production (day 4-8) was observed. Genotype
      A/A showed a significantly longer duration of mechanical ventilation compared to
      genotype T/T. A trend towards an association between the IL-8-251A allele and an
      increased incidence of posttraumatic ARDS was observed (p=0.08). CONCLUSION: This
      data reaffirms a central role of IL-8 in the pathogenesis of ARDS. Furthermore,
      it points towards a genetic predisposition for posttraumatic IL-8 synthesis which
      might also be associated with the development of posttraumatic ARDS.

PMID- 17498968
TI  - Oxygen tension controls the expansion of human CNS precursors and the generation
      of astrocytes and oligodendrocytes.
AB  - Human neural precursor proliferation and potency is limited by senescence and
      loss of oligodendrocyte potential. We found that in vitro expansion of human
      postnatal brain CD133(+) nestin(+) precursors is enhanced at 5% oxygen, while
      raising oxygen tension to 20% depletes precursors and promotes astrocyte
      differentiation even in the presence of mitogens. Higher cell densities yielded
      more astrocytes regardless of oxygen tension. This was reversed by noggin at 5%,
      but not 20%, oxygen due to a novel repressive effect of low oxygen on bone
      morphogenetic protein (BMP) signaling. When induced to differentiate by mitogen
      withdrawal, 5% oxygen-expanded precursors generated 17-fold more oligodendrocytes
      than cells expanded in 20% oxygen. When precursors were expanded at 5% oxygen and
      then differentiated at 20% oxygen, oligodendrocyte maturation was further
      enhanced 2.5-fold. These results indicate that dynamic control of oxygen tension
      regulates different steps in fate and maturation and may be crucial for treating
      neurodegenerative diseases.

PMID- 17498969
TI  - A sensory feedback circuit coordinates muscle activity in Drosophila.
AB  - Drosophila larval crawling is a simple behavior that allows us to dissect the
      functions of specific neurons in the intact animal and explore the roles of genes
      in the specification of those neurons. By inhibiting subsets of neurons in the
      PNS, we have found that two classes of multidendritic neurons play a major role
      in larval crawling. The bipolar dendrites and class I mds send a feedback signal
      to the CNS that keeps the contraction wave progressing quickly, allowing smooth
      forward movement. Genetic manipulation of the sensory neurons suggests that this
      feedback depends on proper dendritic morphology and axon pathfinding to
      appropriate synaptic target areas in the CNS. Our data suggest that coordination
      of muscle activity in larval crawling requires feedback from neurons acting as
      proprioceptors, sending a "mission accomplished" signal in response to segment
      contraction, and resulting in rapid relaxation of the segment and propagation of
      the wave.

PMID- 17498970
TI  - Co-expression of human protein disulfide isomerase (hPDI) enhances secretion of
      bovine follicle-stimulating hormone (bFSH) in Pichia pastoris.
AB  - Bovine follicle-stimulating hormone (bFSH) is a pituitary gonadotropin composed
      of two non-covalently associated polypeptide subunits, which must be
      glycosylated, folded, and assembled as a heterodimer to be biologically active.
      Low-level expression of the recombinant bFSH is the factor that limits its
      usefulness as a superovulation treatment for cows. To increase the production of
      recombinant bFSH, human protein disulfide isomerase (hPDI) was expressed
      simultaneously in engineered Pichia strains. The secretion characteristics of
      bFSH with or without hPDI were examined. The co-expression of bFSH and hPDI is
      increased to 1.56 mg/l of heterodimer in the culture medium, which is 6-fold
      higher when compared with the control strain carrying the bFSH gene only. These
      results may be generally applicable to increase the expression of other
      glycoprotein hormones in yeast.

PMID- 17498971
TI  - Molecular modeling of the myosin-S1(A1) isoform.
AB  - Type II myosin is the molecular motor which drives contraction upon cyclic
      interaction with filamentous actin while consuming ATP. The contemporary
      crystallographic structure of the myosin subfragment-1 (S1) of myosin covers both
      the motor domain of the heavy chain (MHC) as well as the essential (ELC) and
      regulatory light chains (RLC). A part of the N-terminus of the ELC is, however,
      missing in the 3D-models of Type II myosin. The N-terminal domain of the ELC
      comprises interesting functional features since it binds to actin thus
      controlling myosin motor activity. For the first time, we modeled the missing 46
      N-terminal amino acid of the ELC to the contemporary actin-myosin-S1 complex. We
      show a rod-like 91 A structure being long enough to bridge the gap between the
      ELC core of myosin-S1 and the appropriate binding site of the ELC on the actin
      filament.

PMID- 17498972
TI  - Association between preparatory muscle activation and peak valgus knee angle.
AB  - Valgus knee angle (VKA) maybe a predictor of non-contact anterior cruciate
      ligament (ACL) injuries. Pre-programmed muscle activation strategies may exist
      which could contribute to the larger VKA displayed in women compared to men. The
      current study examined the relationship between the peak VKA and preparatory
      muscle activity. Twenty-one adults were asked to perform five trials of a forward
      hop. Lower extremity kinematics and surface EMG were recorded. Peak VKA and EMG
      from 100ms prior to ground contact were used in the data analyses. Three multiple
      linear regressions, where muscle activity was regressed upon the peak VKA, were
      run using subsets (female, male, and male/female) of the sample. Partial
      regression coefficients were considered significant at P0.05. When female
      subjects were exclusively included in the model, a higher peak VKA was associated
      with increased preparatory vastus lateralis and lateral hamstring activity, while
      a lower VKA was associated with increased preparatory vastus medialis activity
      (P0.05). When both genders and males alone were considered, preparatory activity
      was not associated with peak VKA (P0.05). Neuromuscular training promoting equal
      preparatory muscle activity in the medial-to-lateral quadriceps and hamstrings
      may reduce the incidence of ACL injuries in females.

PMID- 17498973
TI  - Inhibition and facilitation in visual word recognition: prefrontal contribution
      to the orthographic neighborhood size effect.
AB  - The recognition of words is a central component of language processing. A major
      role for visual word recognition has been attributed to the orthographic
      neighbors of a word, i.e., words that are orthographically similar to a target
      word. It has been demonstrated that the presence of orthographic neighbors
      facilitates the recognition of words, but hinders the rejection of nonwords. It
      is therefore assumed that representations of orthographic neighbors are at least
      partially activated during word recognition, and that they influence word
      recognition depending on the specific task context. In the present study, we used
      fMRI to examine the neural bases of the effect of orthographic neighborhood size
      on speeded lexical decisions to words and nonwords. Our results demonstrate
      lexicality x neighborhood size interactions in mid-dorsolateral and medial
      prefrontal cortex, suggesting the involvement of a domain-general, extra-lexical
      process for orthographic neighborhood effects on word and nonword processing.
      This result challenges computational models that offer purely lexical accounts of
      the orthographic neighborhood effect and suggests an important role for executive
      control functions during visual word recognition.

PMID- 17498974
TI  - Quantitative diffusion weighted imaging measures in patients with multiple
      sclerosis.
AB  - Diffusion-weighted imaging (DWI) has been proposed as a sensitive measure of
      disease severity capable of detecting subtle changes in gray matter and white
      matter brain compartments in patients with multiple sclerosis (MS). However, DWI
      has been applied to the study of MS clinical subtypes in only a few studies. The
      objective of this study was to demonstrate the validity of a novel, fully
      automated method for the calculation of quantitative DWI measures. We also wanted
      to assess the correlation between whole brain (WB)-DWI variables and clinical and
      MRI measures of disease severity in a large cohort of MS patients. For this
      purpose we studied 432 consecutive MS patients (mean age 44.4+/-10.2 years), 16
      patients with clinically isolated syndrome (CIS) and 38 normal controls (NC)
      using 1.5 T brain MRI. Clinical disease subtypes were as follows: 294 relapsing
      remitting (RR), 123 secondary-progressive (SP) and 15 primary-progressive (PP).
      Mean disease duration was 12+/-10 years. Mean Expanded Disability Status Scale
      (EDSS) was 3.3+/-2.1. Brain parenchymal fraction (BPF), gray matter fraction
      (GMF) and white matter fraction (WMF) were calculated using a fully automated
      method. Mean parenchymal diffusivity (MPD) maps were created. DWI indices of peak
      position (PP), peak height (PH), MPD and entropy (ENT) were obtained. T2- and T1
      lesion volumes (LV), EDSS, ambulation index (AI) and nine-hole peg test (9-HPT)
      were also assessed. MS patients had significantly lower BPF (d=1.26; p<0.001) and
      GMF (d=0.61; p=0.003), and higher ENT (d=1.2; p<0.0001), MPD (d=1.04; p<0.0001)
      and PH (d=0.47; p=0.045) than NC subjects. A GLM analysis, adjusted for age and
      multiple comparisons, revealed significant differences between different clinical
      subtypes for BPF, GMF, ENT, PH, PP, T2-LV and T1-LV (p<0.0001), WMF (p=0.001) and
      MPD (p=0.023). In RR and SP MS patients, ENT showed a more robust correlation
      with other MRI (r=0.54 to 0.67, p<0.0001) and clinical (r=0.31 to 0.36, p<0.0001)
      variables than MPD (r=0.23 to 0.41, p<0.001 for MRI and r=0.13 to 0.18; p=0.006
      to p<0.001 for clinical variables). The GMF and BPF showed a slightly stronger
      relationship with all clinical variables (r=0.33 to 0.48; p<0.0001), when
      compared to both lesion and DWI measures. ENT (R2=0.28; p<0.0001) and GMF
      (R2=0.26; p<0.001) were best related with SP disease course. This study
      highlights the validity of DWI in discerning differences between NC and MS
      patients, as well as between different MS subtypes. ENT is a sensitive marker of
      overall brain damage that is strongly related to clinical impairment in patients
      with SP MS.

PMID- 17498975
TI  - Memory and the medial temporal lobe: hemispheric specialization reconsidered.
AB  - The role of the medial temporal lobe in learning and memory has been well
      established in research on humans and other animals. In humans, clinical and
      neuroimaging studies typically suggest material-specific lateralization in which
      the left and right temporal lobes are associated with verbal and nonverbal
      memory, respectively. It is often assumed that the temporal lobes are
      functionally alike, differing only in terms of the content to be learned. Here we
      present data that challenge this notion, showing that the type of material used
      during a memory task can influence fMRI activation patterns beyond the expected
      left-verbal/right-nonverbal dichotomy. Our results also suggest some degree of
      functional asymmetry in the medial temporal lobe that is independent of material
      type, pointing to underlying processing differences between the left and right
      temporal lobes.

PMID- 17498977
TI  - Mechanical fragmentation and transportation of calcium phosphate substrate by
      filopodia and lamellipodia in a mature osteoclast.
AB  - The functions of filopodia and lamellipodia in mature osteoclasts are not well
      known in the process of bone resorption. We investigated the function of
      filopodial/lamellipodial movement in mature osteoclasts by video-enhanced
      contrast-differential interference contrast (VEC-DIC) microscopy. Mature
      osteoclasts, which were isolated from Japanese white rabbits, were cultured on
      calcium phosphate (CP)-coated quartz coverslips to observe
      filopodial/lamellipodial movement and the formation of CP-free areas precisely.
      Filopodia broke the CP substrate into pieces and transported them to the cell
      body by capturing them at the tip. Lamellipodia destroyed the CP substrate, and
      transported it to the cell body by capturing small particles in a mass. This
      study suggests two functions of filopodia and lamellipodia in mature osteoclasts,
      i.e., the mechanical fragmentation of the CP substrate and the transportation of
      the CP particles to the cell body.

PMID- 17498978
TI  - Analysis of aclarubicin-induced cell death in human fibroblasts.
AB  - In the present study we investigated the mode of cell death induced by
      aclarubicin (ACL) in trisomic (BB) and normal (S-2) human fibroblasts. Cells were
      incubated with ACL for 2h and then cultured in drug-free medium for up to 96h.
      Using fluorescence microscopy, agarose gel electrophoresis and comet assay we
      demonstrate that ACL induced time-dependent morphological and biochemical changes
      in both cell types. The population of apoptotic cells, analysed by acridine
      orange and ethidium bromide nuclear staining reached its maximum at 24-48h.
      Prolonged post-treatment time progressively increased the level of necrotic
      cells. At 24-48h time points we also observed a significant increase in caspase-3
      activity, oligonucleosomal DNA fragmentation and DNA strand breaks. Cotreatment
      of cells with the specific caspase-3 inhibitor Ac-DEVD-CHO partly reduced the
      extent of apoptosis and necrosis and DNA degradation. In conclusion, trisomic and
      normal fibroblasts demonstrate similar response to aclarubicin treatment. Drug
      induced the apoptotic and necrotic pathway of cell death that was mediated by
      caspase-3.

PMID- 17498976
TI  - The beneficial effect of delayed compressive loading on tissue-engineered
      cartilage constructs cultured with TGF-beta3.
AB  - OBJECTIVE: To determine whether the functional properties of tissue-engineered
      constructs cultured in a chemically-defined medium supplemented briefly with TGF
      beta3 can be enhanced with the application of dynamic deformational loading.
      METHODS: Primary immature bovine cells (2-3 months old) were encapsulated in
      agarose hydrogel (2%, 30 x 10(6)cells/ml) and cultured in chemically-defined
      medium supplemented for the first 2 weeks with transforming growth factor beta 3
      (TGF-beta3) (10 microg/ml). Physiologic deformational loading (1 Hz, 3 h/day, 10%
      unconfined deformation initially and tapering to 2% peak-to-peak deformation by
      day 42) was applied either concurrent with or after the period of TGF-beta3
      supplementation. Mechanical and biochemical properties were evaluated up to day
      56. RESULTS: Dynamic deformational loading applied concurrently with TGF-beta3
      supplementation yielded significantly lower (-90%) overall mechanical properties
      when compared to free-swelling controls. In contrast, the same loading protocol
      applied after the discontinuation of the growth factor resulted in significantly
      increased (+10%) overall mechanical properties relative to free-swelling
      controls. Equilibrium modulus values reach 1306+/-79 kPa and glycosaminoglycan
      levels reach 8.7+/-1.6% w.w. during this 8-week period and are similar to host
      cartilage properties (994+/-280 kPa, 6.3+/-0.9% w.w.). CONCLUSIONS: An optimal
      strategy for the functional tissue engineering of articular cartilage,
      particularly to accelerate construct development, may incorporate sequential
      application of different growth factors and applied deformational loading.

PMID- 17498979
TI  - Werner syndrome helicase (WRN), nuclear DNA helicase II (NDH II) and histone
      gammaH2AX are localized to the centrosome.
AB  - Werner syndrome helicase (WRN) was found in the centrosome of human cells, both
      in interphase and in mitosis. Nuclear DNA helicase II (NDH II), also called RNA
      helicase A (RHA), an interaction partner of WRN, was also present in the
      centrosome. NDH II localized to the centrosome in interphase but left the
      centrosome with the ongoing progression of mitosis. The localization of NDH II to
      the centrosome was hardly affected by cytochalasin D that depolymerizes actin
      filaments. In contrast, treatment by the microtubules disrupting agent nocodazole
      strikingly detached NDH II from the centrosome, which was in contrast to WRN that
      remained there under this condition. Treatment of cells with the DNA damaging
      agent 4-nitroquinoline-1-oxide (4NQO) released NDH II, but not WRN from the
      centrosome. Surprisingly, the double-stranded DNA break repair-induced histone
      variant gammaH2AX was also found in centrosomes of interphase and mitotic cells.
      Following DNA damage by 4NQO, gammaH2AX left the centrosome with similar kinetics
      as NDH II. In vitro pull-down assays confirmed a direct physical interaction
      between these two proteins. Since NDH II associated with gammaH2AX after DNA
      damage, we suggest that complex formation between NDH II and gammaH2AX may occur
      in pre-assembled complexes at the centrosome, which are subsequently recruited to
      sites of damaged DNA for inducing the repair process.

PMID- 17498980
TI  - Delirium in vascular surgery.
AB  - Delirium is common in many surgical settings. Patients undergoing elective
      vascular surgery may be at particular risk of developing delirium, and may have
      modifiable aetiological factors that can be addressed by pre-operative
      interventions. We decided to review the literature regarding the incidence and
      aetiology of delirium in elective vascular surgical patients. METHODS: We
      searched medical databases, journals and bibliographies to identify relevant
      studies. We used predetermined quality criteria for appraisal of the quality of
      incidence and aetiological studies. RESULTS: Four studies were identified as
      relevant to the review. The incidence of delirium ranged from 29.1% to 39.2%. The
      significant aetiological factors identified were age, pre-operative cognitive
      impairment, depressive symptoms, inter-operative blood transfusion and previous
      amputation. CONCLUSIONS: Delirium is common in people undergoing elective
      vascular surgery. Further research is required to examine the effect on outcome
      of delirium, and the effect of psychiatric and geriatric medicine interventions
      in this setting.

PMID- 17498981
TI  - Nightmares: a new neurocognitive model.
AB  - Nightmares are a prevalent parasomnia associated with a range of psychiatric
      conditions and pathological symptoms. Current knowledge about how nightmares are
      produced is still influenced by neo-psychoanalytic speculations as well as by
      more recent personality, evolutionary and neurobiological models. A majority of
      these models stipulate some type of emotionally adaptive function for dreaming,
      e.g., image contextualization, affect desomatization, mood regulation or fear
      extinction. Nightmares are widely seen to be either an intensified expression of
      an emotionally adaptive function or, conversely, as evidence of its breakdown.
      Our recent, affective network dysfunction (AND) model, integrates the tenets of
      many prior models in proposing that nightmares reflect problems with the fear
      extinction function of dreaming. This new model accounts for a wide range of
      dysphoric dream imagery (bad dreams, idiopathic nightmares, post-traumatic
      nightmares) and incorporates recent findings in the areas of brain imaging, sleep
      physiology, PTSD, anxiety disorders and the consolidation and extinction of fear
      memories.

PMID- 17498982
TI  - A deletion in the R region of long terminal repeats in small ruminant
      lentiviruses is associated with decreased pathology in the lung.
AB  - A particular variant of the maedi visna virus (MVV) that although present in
      blood causes no clinical signs in infected sheep has been described. This variant
      carries a 13-14 nucleotide deletion in the R region of the proviral long terminal
      repeats. The hypothesis that this specific deletion may be associated with low
      pathogenicity has been investigated by comparing the distribution of proviral
      sequences, the histopathological lesions and the expression of viral proteins in
      the brain, lungs and udders of sheep naturally infected with viral strains
      carrying the deletion. Provirus could be demonstrated in most of the tissues
      examined from sheep infected with either type of virus, and the tissue-derived
      virus carried the typical deletion in the study flock animals. Histopathological
      analysis revealed that the lungs were significantly less affected in the animals
      infected with virus carrying the deletion. Concomitantly, viral expression was
      significantly reduced in the lungs of these animals. The findings suggest that
      the reduced pathogenicity of MVV with the specific deletion in the R region is
      not due to a restriction in the availability of specific tissues to infection,
      but is associated with a reduced capacity for viral expression in the lungs.

PMID- 17498983
TI  - J-Stabilization of singlet states in the solution NMR of multiple-spin systems.
AB  - Long-lived singlet states have been observed in the solution NMR of spin systems
      containing more than two coupled spins, despite the fact that the singlet state
      is expected to be quenched by small long-range J-couplings. We show that the
      stability of localized singlet states may be explained by taking into account the
      intra-pair J-coupling between the two spins which participate in the singlet
      state. The relatively strong intra-pair J-coupling protects the singlet state
      against quenching by weaker out-of-pair J-couplings.

PMID- 17498984
TI  - Study of diffusion in erythrocyte suspension using internal magnetic field
      inhomogeneity.
AB  - Transport of water and ions through cell membranes plays an important role in
      cell metabolism. We demonstrate a novel technique to measure water transport
      dynamics using erythrocyte suspensions as an example. This technique takes
      advantage of inhomogeneous internal magnetic field created by the magnetic
      susceptibility contrast between the erythrocytes and plasma. The decay of
      longitudinal magnetization due to diffusion in this internal field reveals multi
      exponential behavior, with one component corresponding to the diffusive exchange
      of water across erythrocyte membrane. The membrane permeability is obtained from
      the exchange time constant and is in good agreement with the literature values.
      As compared to the other methods, this technique does not require strong
      gradients of magnetic field or contrast agents and, potentially, can be applied
      in vivo.

PMID- 17498985
TI  - Infantile high myopia in Bohring-Opitz syndrome.
AB  - Bohring-Opitz syndrome is a rare genetic condition of uncertain inheritance. It
      was first delineated by Bohring and coworkers in 1999 and up to 15 possible cases
      have been reported. It has both ophthalmic and systemic features and represents a
      unique syndrome considered to be distinct from Opitz C trigonocephaly syndrome.
      The classic features of Bohring-Opitz syndrome include prominent metopic suture,
      exophthalmos, hypertelorism, cleft lip and palate, flexion deformities of the
      upper limbs, nevi flammei, and significant neurodevelopmental delay. We report a
      child with Bohring-Opitz syndrome and infantile high myopia. Bohring's original
      description of the phenotype did not include myopia but since then both this case
      and two others have reported this association. The presence of high myopia may be
      helpful in identifying suitable candidate genes and elucidating the genetic
      mechanism, as well as alerting ophthalmologists to the importance of refraction
      for affected children.

PMID- 17498986
TI  - Presenting features suggestive for later recurrence of idiopathic sixth nerve
      paresis in children.
AB  - BACKGROUND: Although idiopathic sixth (abducens) nerve paresis of childhood
      typically resolves within a few months, the paresis recurs in a minority of
      cases. The purpose of this study is to describe clinical features at presentation
      that are associated with later recurrence. METHODS: Retrospective literature
      review and novel case report. RESULTS: Thirty-five articles were reviewed,
      revealing 54 nonrecurrent and 41 recurrent cases. One previously unreported
      recurrent case is also included in our review. Patients with recurrence were
      typically girls (p < 0.05) and were typically affected in the left eye (p <
      0.05). All children who initially presented under 14 months of age and/or whose
      initial presentation was associated with vaccination developed recurrence.
      Seventy-three percent of second episodes occurred within one year of initial
      presentation. No children who initially presented after 12 years of age developed
      recurrence. CONCLUSIONS: When an otherwise normal child is diagnosed with
      idiopathic sixth nerve paresis, clinical features suggestive of later recurrence
      are female gender, left eye involvement, younger age, and recent vaccination.
      Recurrence is less likely if it has not occurred within one year of the initial
      event.

PMID- 17498987
TI  - Incidence, progression, and duration of retinopathy of prematurity in Hispanic
      and white non-Hispanic infants.
AB  - PURPOSE: To compare the incidence, progression, and duration of retinopathy of
      prematurity (ROP) in low-birth-weight Hispanic and white non-Hispanic infants.
      METHODS: A total of 671 white non-Hispanic infants and 128 Hispanic infants with
      birth weights less than 1751 g were retrospectively evaluated to determine the
      incidence of both ROP and subthreshold or worse ROP. Multiple regression analysis
      was used to control for birth weight, gestational age at birth, year of birth,
      and newborn intensive care unit as contributing factors in the risk of ROP. The
      duration of ROP in untreated infants was calculated and compared for the two
      ethnic groups. RESULTS: There was no significant difference in the percentage of
      infants with ROP in the white non-Hispanic group (38.3%) versus the Hispanic
      group (41.4%). There was also no significant difference between white non
      Hispanics (11.8%) and Hispanics (15.6%) in the risk of developing subthreshold or
      worse ROP. Multiple regression analysis showed no contribution of ethnicity to
      the risk of developing ROP (t = -0.34, p = 0.74) or subthreshold or worse ROP (t
      = 0.75, p = 0.45). The average duration of untreated ROP in white non-Hispanics
      (8.6 +/- 5.4 weeks) and Hispanics (8.9 +/- 7.0 weeks) also was not significantly
      different. However, Hispanic infants showed significantly higher variance in
      duration than white non-Hispanic infants (p = 0.04). CONCLUSIONS: ROP occurs with
      similar frequency in Hispanic and white non-Hispanic premature infants, as does
      subthreshold or worse ROP. Some Hispanic infants had an unusually short or long
      duration of ROP before regression, implying that the natural history of ROP may
      be somewhat different for the two ethnic groups.

PMID- 17498988
TI  - Botulinum toxin in the management of internuclear ophthalmoplegia.
AB  - BACKGROUND: Internuclear ophthalmoplegia (INO) presents as a complex ocular
      motility problem due to medial longitudinal fasciculus damage. The symptoms are
      disabling and challenging to manage. We evaluate the efficacy of botulinum toxin
      in the management of INO. METHODS: A retrospective review of 16 patients with INO
      managed by botulinum toxin A injection into one or more extraocular muscles over
      the past 20 years was performed. The age, sex, etiology, symptoms, angle of
      deviation, and binocular function pre- and postinjection were analyzed. RESULTS:
      The mean age at presentation was 45.1 years with a male/female ratio of 9:7. The
      most common etiologies included brainstem hemorrhage in five and multiple
      sclerosis in four. After injection diplopia reduced in 14 (87.5%), appearance
      improved in 9 (56.3%), and the head posture improved in 4 (25%). Convergence
      recovered in two patients (12.5%) and stereopsis improved in three patients
      (18.8%). Complications included transient ptosis in one patient, and one patient
      had an overcorrection. Two patients complained of transient vertical diplopia
      that resolved within 3 weeks. At final follow-up, five (31.5%) patients continued
      on maintenance injections, three (18.8%) were stable and discharged, while the
      rest were managed by occlusion (five), prisms (one), or surgery (two).
      CONCLUSIONS: We report on the management of INO by botulinum toxin. Benefit was
      noted in terms of reduced diplopia and occasionally improved binocular function.
      Though the benefits are limited by the need for repeated injections, for patients
      with this debilitating condition, botulinum toxin provides some symptomatic
      relief.

PMID- 17498989
TI  - Fluorescein angiographic findings in a male infant with incontinentia pigmenti.
AB  - Incontinentia pigmenti is a rare, X-linked dominant, genodermatosis and is almost
      always lethal in males. It is characterized by cutaneous, ocular, dental, and
      central nervous system (CNS) abnormalities and about 35% of patients develop some
      form of ocular abnormality, which may include retinal vascular abnormalities,
      ischemic retinal infarctions, retinal detachments, cataracts, uveitis,
      strabismus, and nystagmus. Incontinentia pigmenti has been linked to the NEMO
      gene, which is mapped to Xq28.

PMID- 17498990
TI  - Conformational analysis of compstatin analogues with molecular dynamics
      simulations in explicit water.
AB  - The cyclic 13-residue peptide compstatin is a potential therapeutic agent against
      the unregulated activation of the complement system. A thorough knowledge of its
      structural and dynamical properties in solution may assist the design of improved
      complement inhibitors. NMR studies have suggested that the 5-8 segment of free
      compstatin folds into a critical for activity 5-8 beta turn and the rest of the
      peptide is mainly disordered. Earlier computational studies of compstatin
      analogues with a polar-hydrogen/generalized-Born approximation reproduced the 5-8
      turn, but also indicated the formation of beta-hairpin or alpha-helical elements
      and the existence of interactions between certain charged or aromatic sidechains.
      However, these features are absent or partly present in the NMR spectra, due to
      extensive conformational averaging. In order to check the compstatin properties
      with a more rigorous model of the intra- and intermolecular interactions, we
      conduct here 98-ns all-atom/explicit-water simulations of three compstatin
      analogues with variable activity; a native analogue, the more active mutant
      V4W/H9A and the inactive mutant Q5G. The 5-8 beta-turn population is in good
      accord with NMR. For the systems studied here, the simulations suggest that the 5
      8 turn population does not correlate strictly with activity, in agreement with
      earlier mutational studies. Furthermore, they show structural differences among
      the analogues outside the 5-8 region. The possible role of these differences in
      activity is discussed. The probability of beta-hairpin or alpha-helix elements is
      much smaller with respect to the polar-hydrogen/GB simulations, and the
      persistent Trp4-Trp7 or Asp6-Arg11 sidechain interactions of the earlier GB
      studies are not reproduced. The present simulations extend the NMR data and
      improve our understanding of the properties of compstatin and related analogues.

PMID- 17498991
TI  - Growth hormone modulates the degradative capacity of muscle nucleases but not of
      cathepsin D in post-weaning mice.
AB  - We determined whether recombinant human growth hormone (rhGH) administration
      might modulate the enzyme degradative capacity of the muscle lysosomal system and
      influence muscle growth. Muscle cathepsin D, acid RNase and DNase II activities
      are determined in the gastrocnemius muscle of rhGH-treated post-weaning female
      BALB/c mice. Linear regressions were used to analyze the relationships of each
      enzyme with their respective substrate. GH induced a depletion-recovery response
      of muscle growth through a mechanism which is similar to catch-up growth. In
      these conditions, cathepsin D activity decreased with age in all animals (GH:
      40%; saline: 79%), showing a substantial developmental decline that could reflect
      changes in the rate of protein breakdown. However, the degradative capacity of
      cathepsin D was paradoxically unmodified in rhGH-mice compared with saline mice
      (according to the enzyme vs. substrate linear regression slope), in spite of the
      increase in enzyme activity elicited by GH. This suggests that the muscle protein
      breakdown is not increased by GH-treatment in post-weaning mice. The enhancement
      of muscle protein deposition as indicated by the augmented muscle cell size
      (protein:DNA ratio) of rhGH-mice (increased 178% from 25 to 50 days) vs. saline,
      can be attributed to a higher muscle K(RNA). In contrast, acid RNase and DNase II
      activities directly participate in muscle RNA and DNA degradation. Both nucleases
      were inhibited by GH treatment (a decrease of 48% and 63%, respectively, vs.
      saline at 50 days). The decrease in RNase activity suggests an inverse relation
      between the rate of protein synthesis (high) and acid RNase activity (low),
      leading to spare muscle RNA for synthesizing protein during catch-up growth.
      Also, low DNase II activity could contribute to inhibiting of muscle DNA
      degradation, facilitating muscle growth. Thus, GH seems to act as a direct
      modulator of the degradative capacity of skeletal muscle nucleases but not of
      cathepsin D, influencing DNA and RNA degradation during the depletion-recovery
      response to GH of gastrocnemius muscle in female post-weaning mice.

PMID- 17498993
TI  - Comparison of a new device for blood sampling in cats with a vacuum tube
      collection system - plasma biochemistry, haematology and practical usage
      assessment.
AB  - Using paediatric devices to collect venous blood from a cephalic vein in cats
      offers numerous practical advantages over traditional jugular venepuncture and
      vacuum closed systems: minimal restraint is required; there is minimal risk of
      serious injury to the cat; the discomfort associated with venepuncture is reduced
      by the use of small diameter (25 gauge) needles; very small volumes (200 microl)
      of blood are extracted; and the risk of vein collapse or haematoma is low. The
      aim of this study was to compare the haematological and plasma chemistry results
      obtained from six healthy cats using the two sampling techniques. Five plasma
      biochemical analytes were measured and a complete haematological examination was
      performed on each specimen. No clinically relevant difference between the two
      blood sampling techniques was observed for any variable, indicating that
      paediatric devices provide a useful alternative to vacuum tubes for venous blood
      collection in the cat.

PMID- 17498992
TI  - Murine model (Galns(tm(C76S)slu)) of MPS IVA with missense mutation at the active
      site cysteine conserved among sulfatase proteins.
AB  - Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by
      deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), required for
      degradation of keratan sulfate and chondroitin-6-sulfate. In order to study the
      effects of a missense mutation in the active site cysteine in the GALNS gene that
      is conserved in all mammalian sulfatases, we produced a p.C76S (an active site
      replacement) knock-in mouse by replacing the Cys76 with Ser in the endogenous
      murine Galns by targeted mutagenesis. Homozygous Galns(tm(C76S)slu) mice had no
      detectable GALNS enzyme activity. At age of 2-4 months, lysosomal storage was
      present primarily within reticuloendothelial cells such as Kupffer cells and
      spleen sinusoidal lining cells. Vacuolar change was present in glomerular
      visceral epithelial cells and was not present in hepatocytes or renal tubular
      cells. In the brain, hippocampal and neocortical neurons and meningeal cells
      showed lysosomal storage. Radiographs revealed no change in the skeletal bones of
      mice up to 12 months old. Thus, the Galns(tm(C76S)slu) mice had visceral storage
      of GAGs in organs but lacked the skeletal features of human MPS IVA. In contrast
      to a previously reported transgenic model (Galns(tm(hC79S.mC76S)slu)), in which
      the inactive human GALNS transgene was overexpressed, no reduction in other
      sulfatases was observed. In addition, the Galns(tm(C76S)slu) mice displayed
      milder storage. We conclude that the milder phenotype is characteristic of
      isolated GALNS deficiency while the more severe phenotype reflected in the
      Galns(tm(hC79S.mC76S)slu) mice was due to deficiency of other sulfatases caused
      by oversaturation of the sulfate modifying enzyme by the inactive human gene
      product.

PMID- 17498994
TI  - Prevalence of the polycystic kidney disease and renal and urinary bladder
      ultrasonographic abnormalities in Persian and Exotic Shorthair cats in Italy.
AB  - The ultrasonographic findings of kidneys, liver and urinary bladder of 288
      Persian and 44 Exotic Shorthair clinically normal cats that underwent screening
      for polycystic kidney disease (PKD) between July 2003 and December 2005 were
      reviewed. Cats were divided into two groups, one including cats aged <9 months
      (group 1) and one cats aged >/=9 months (group 2). Cats were classified as PKD
      positive when at least one renal cyst was found. One hundred and thirty-six cats
      (41.0%) had more than one cyst in at least one kidney. The prevalence of PKD was
      similar in both groups. Eight PKD-positive cats had cystic livers (5.9%). Other
      renal abnormalities included a pelvic calculus and a medullary rim sign (MRS).
      The difference in prevalence of an MRS in group 2 compared to group 1 and the
      difference between PKD-positive and -negative cats in group 2 were not
      significant. There was no difference in mean kidney length between PKD-positive
      and -negative cats in group 2. Urinary bladder anomalies were principally
      represented by urinary sediment, with prevalence significantly higher in group 2.
      No difference was detected in group 2 between PKD-positive and -negative cats. In
      conclusion feline PKD is common in Italy. The ultrasonographic findings of MRS
      and urinary bladder sediment did not correlate with feline PKD. Urinary bladder
      sediment is common in Persians and Exotic Shorthairs and more likely in adults.

PMID- 17498995
TI  - [Use of intravenous polyclonal immunoglobulins in autoimmune and inflammatory
      disorders].
AB  - Initially used for the treatment of immunodeficiencies, intravenous
      immunoglobulins (IVIg) have increasingly been used as immunomodulatory agent in
      autoimmune and inflammatory disorders. The mode of action of IVIg is enigmatic,
      probably involving Fc-dependent and/or F(ab')2-dependent non-exclusive mechanisms
      of action. IVIg broadly interacts with the different components of the immune
      system: cytokines, complement, Fc receptors and several cell surface
      immunocompetent molecules. IVIg also has an impact on effector functions of
      immune cells. These mechanisms of action of IVIg reflect the importance of
      natural antibodies in the maintenance of immune homeostasis. We discuss here the
      recent advances in the understanding of immunoregulatory effects of IVIg, and we
      pointed out the need of new strategies to overcome the predicted increasing
      worldwide shortage of IVIg.

PMID- 17498996
TI  - [Sentinel node biopsy in cervical cancer: state-of-the-art in 2007].
AB  - In cervical cancer, lymph node status is a major prognostic factor and a decision
      criterion for adjuvant therapy warranting the lymphadenectomy. The sentinel node
      procedure, which has emerged to reduce morbidity of extensive lymphadenectomy,
      remains a major step in the surgical management of solid cancers. Sentinel node
      procedure has become a standard technique for the determination of the nodal
      stage of the disease in patients with melanoma, vulvar cancer and recently in
      breast cancer. In cervical cancer, the sentinel node biopsy is still at the stage
      of feasibility. In this article, we review the technical aspects, results and
      clinical implications of sentinel node procedure in cervical cancer.

PMID- 17498997
TI  - Concept of a platform-based impact isolation system for protection of wheelchair
      occupants from injuries in vehicle crashes.
AB  - To improve the protection of a wheelchair-seated person with disabilities
      traveling in a vehicle from injuries in a crash, it is proposed to attach the
      wheelchair to a movable platform separated from the vehicle body by means of a
      shock isolator. The control of the platform is designed to reduce the occupant's
      injury risk, as compared with the case of the attachment of the wheelchair
      directly to the vehicle. The isolator design is based on the minimization of the
      force transmitted to the wheelchair occupant, provided that the space allowed for
      the platform to move relative to the vehicle is constrained. The possibility of
      pre-acting control, when the isolator is engaged for a time prior to the crash,
      is discussed. Passive tiedown and restraint systems are studied, although it is
      recognized that active systems could provide even lower injury risks. A multibody
      model of the platform-based occupied wheelchair is utilized for full-scale
      simulation of the response of the system to a crash pulse. The simulation shows a
      noticeable reduction in the injury risk due to the platform and an even greater
      reduction of injury with pre-acting control.

PMID- 17498998
TI  - Contact lens-induced changes in the anterior eye as observed in vivo with the
      confocal microscope.
AB  - The availability of the confocal microscope over the past decade has allowed
      clinicians and researchers to refine their understanding of the physiological and
      pathological basis of the ocular response to contact lens wear, and to discover
      previously unknown phenomena. Mucin balls, which form in the tear layer in
      patients wearing silicone hydrogel lenses, can penetrate the full thickness of
      the epithelium, leading to activation of keratocytes in the underlying anterior
      stroma. Epithelial cell size increases in response to all forms of lens wear,
      with lenses of higher oxygen transmissibility (Dk/t) interfering least with the
      normal process of epithelial desquamation. A higher density of Langerhans' cells
      is observed in the layer of the sub-basal nerve plexus among contact lens
      wearers, suggesting that contact lens wear may be altering the immune status of
      the cornea. Dark lines and folds are observed in the oedematous cornea in
      response to contact lens wear. Mechanical stimulation of the corneal surface, due
      to the physical presence of a contact lens, and the consequent release of
      inflammatory mediators, is the likely cause of reduced keratocyte density
      associated with lens wear. Highly reflective stromal 'microdot deposits' are
      observed throughout the entire stroma in higher numbers in lens wearers. 'Blebs'
      in the endothelium have a bright centre surrounded by a dark annular shadow; this
      appearance is explained with the aid of an optical model. The confocal microscope
      has considerable clinical utility in diagnosing Acanthamoeba and fungal
      keratitis. At the limbus, contact lenses can induce structural changes such as
      increases in basal epithelial cell size. An increased number of rolling
      leucocytes is observed in limbal vessels in response to low Dk/t lenses. It is
      concluded that the confocal microscope has considerable utility in contact lens
      research and practice.

PMID- 17498999
TI  - Neighborhood and developmental differences in children's perceptions of
      opportunities for play and physical activity.
AB  - The purposes of this study were to examine perceptions of places to play and be
      physically active among children from two different urban neighborhoods, and
      evaluate these perceptions for age-related developmental differences. One hundred
      and sixty-eight children from grades K-6 (aged 6-12 years old) completed mental
      maps depicting places where they could play and be physically active. The
      children were recruited from schools in two neighborhoods-one a high-walkability
      (H-W) grid-style neighborhood, the other a low-walkability (L-W) lollipop-style
      (i.e., cul-de-sacs) neighborhood. Analysis revealed that children in the H-W
      neighborhood depicted more active transportation and less non-active
      transportation than children in the L-W neighborhood. Children in the lowest
      grades (K-2) in the L-W neighborhood depicted more play in the home/yard
      environment than the oldest children, more good weather image events than
      children in Grades 3-6, and less play outside the home/yard environment than
      children in Grades 3 and 4. In the H-W neighborhood, the youngest children (K-2)
      depicted significantly less play in the home/yard environment and less play
      outside the home/yard environment than older children (Grades 3-6). Thus, both
      the type of urban neighborhood and children's age moderated perceptions of places
      to play and be physically active.

PMID- 17499000
TI  - Comparative DNA methylation analysis in normal and tumour tissues and in cancer
      cell lines using differential methylation hybridisation.
AB  - Immortalized human cancer cell lines are widely used as tools and model systems
      in cancer research but their authenticity with regard to primary tissues remains
      a matter of debate. We have used differential methylation hybridisation to obtain
      comparative methylation profiles from normal and tumour tissues of lung and
      colon, and permanent cancer cell lines originally derived from these tissues.
      Average methylation differences only larger than 25% between sample groups were
      considered for the profiles and with this criterion approximately 1000 probesets,
      around 2% of the sites represented on the array, indicated differential
      methylation between normal lung and primary lung cancer tissue, and approximately
      700 probesets between normal colon and primary colon cancer tissue. Both hyper-
      and hypomethylation was found to differentiate normal tissue from cancer tissue.
      The profiles obtained from these tissue comparisons were found to correspond
      largely to those from the corresponding cancer cell lines, indicating that the
      cell lines represent the methylation pattern of the primary tissue rather well.
      Moreover, the cancer specific profiles were found to be very similar for the two
      tumour types studied. Tissue specific differential methylation between lung and
      colon tissues, in contrast, was found to be preserved to a larger extent only in
      the malignant tissue, but was not preserved well in the cancer cell lines
      studied. Overall, our data therefore provide further evidence that permanent cell
      lines are good model systems for cancer specific methylation patterns, but
      deviate with regard to tissue-specific methylation.

PMID- 17499001
TI  - HDAC inhibitors induce apoptosis in glucocorticoid-resistant acute lymphatic
      leukemia cells despite a switch from the extrinsic to the intrinsic death
      pathway.
AB  - Inhibitors of histone deacetylases (HDACi's) are promising novel tools for cancer
      therapy. We have compared the growth inhibitory and apoptogenic potential of the
      pan-HDACi SAHA and the sub-class I selective HDAC inhibitor MS275, as well as
      valproic acid (VPA) on glucocorticoid sensitive and resistant B (B-ALL) and T (T
      ALL) cell acute lymphoblastic leukemia cells and patients blasts. In contrast, to
      our previous results with U937 acute myeloid leukemia (AML) cells which showed a
      similar activity of MS275 and SAHA in growth inhibition and apoptosis induction,
      both B and T-ALL cells were much more efficiently killed by SAHA and VPA than by
      MS275. The same relative potency was observed with some patient ALL blasts
      treated ex vivo. SAHA displayed similar efficacy on glucocorticoid-sensitive and
      insensitive ALL cells but did not synergize with dexamethasone. In studying
      mediators of apoptosis we found that the TRAIL receptor DR5 is constitutively
      expressed in glucocorticoid-sensitive CEM-C7 cells which are also TRAIL
      sensitive. In contrast, glucocorticoid-insensitive CEM-C1 cells do not express
      DR5 and are insensitive to TRAIL. However, SAHA induces, in addition to
      p21(WAF1/CIP1) also re-expression of DR5. Importantly, SAHA-induced apoptosis of
      CEM-C7 cells operates through initiator caspase 10, while it induces apoptosis of
      CEM-C1 cells through the intrinsic, as well as through caspase-independent death
      pathways. Our data suggest that the generation of resistance to glucocorticoids
      has dramatically altered death signaling in these cells and that SAHA overcomes
      these restrictions by inducing alternative death pathways.

PMID- 17499002
TI  - MDM2 and MDM4: p53 regulators as targets in anticancer therapy.
AB  - The gene TP53, encoding transcription factor p53, is mutated or deleted in half
      of human cancers, demonstrating the crucial role of p53 in tumor suppression.
      Importantly, p53 inactivation in cancers can also result from the
      amplification/overexpression of its specific inhibitors MDM2 and MDM4 (also known
      as MDMX). The presence of wild-type p53 in those tumors with MDM2 or MDM4
      overexpression stimulates the search for new therapeutic agents to selectively
      reactivate it. This short survey highlights recent insights into MDM2 and MDM4
      regulatory functions and their implications for the design of future p53-based
      anticancer strategies. We now know that MDM2 and MDM4 inhibit p53 in distinct and
      complementary ways: MDM4 regulates p53 activity, while MDM2 mainly regulates p53
      stability. Upon DNA damage, MDM2-dependent degradation of itself and MDM4
      contribute significantly to p53 stabilization and activation. These and other
      data imply that the combined use of MDM2 and MDM4 antagonists in cancer cells
      expressing wild-type p53 should activate p53 more significantly than agents that
      only antagonize MDM2, resulting in more effective anti-tumor activity.

PMID- 17499003
TI  - Glycolysis in cancer: a potential target for therapy.
AB  - Clinical imaging of primary and metastatic cancers with Fluoro deoxy-d-Glucose
      Positron Emission Tomography (FdG PET) has clearly demonstrated that increased
      glucose flux compared to normal tissue is a common trait of human malignancies
      (Gambhir, 2002) This is a consequence of a shift of glucose metabolism to less
      efficient glycolytic pathways in response to regional hypoxia and evolution of
      aerobic glycolysis in many cancer phenotypes. This distinctive metabolic profile
      presents an inviting target for cancer treatment and prevention. Here, we
      summarize the therapeutic strategies under investigation to exploit or interrupt
      tumor glycolytic metabolism. Although a number of approaches are under
      investigation, none has been sufficiently successful to warrant widespread
      clinical application. We point out that the environmental heterogeneity and
      evolutionary capacity of tumor cells that likely led to development of
      upregulated glycolysis could also promote adaptive strategies that confer
      resistance to therapies designed to inhibit glucose metabolism.

PMID- 17499004
TI  - The tify family previously known as ZIM.
AB  - The ZIM domain was originally identified in the ZIM protein (BAA97679; Zinc
      finger protein expressed in Inflorescence Meristem). Since then it has been found
      in other proteins and the corresponding genes have been grouped into a plant
      specific family. However, the family lacks consistency in its classification
      among different databases. Here, we try to clarify this incongruity by presenting
      an overview of the Arabidopsis proteins having this domain. The presented genome
      wide survey can be seen as a start point to reveal the unknown function of these
      proteins. Furthermore, because of the confusing ZIM nomenclature being used at
      present, we propose to rename the domain and family as tify, after the most
      conserved amino acid motif characterizing the members of this family.

PMID- 17499005
TI  - Plastoglobules: versatile lipoprotein particles in plastids.
AB  - Plastoglobules are plastid-localized lipoprotein particles that contain
      tocopherols and other lipid isoprenoid-derived metabolites, as well as structural
      proteins named plastoglobulins. Surprisingly, recent publications show that
      plastoglobules contain enzymes involved in the metabolism of these secondary
      metabolites, as well as enzymes of unknown function. The size and number of
      plastoglobules vary during plastid development and differentiation, and strongly
      increase during light stress, senescence and in mutants blocked in thylakoid
      formation. Given that plastoglobules are contiguous with the outer lipid leaflet
      of the thylakoid membrane, it is highly plausible that a function of
      plastoglobules is the active channeling of lipid molecules and lipid breakdown
      products. Understanding the function of plastoglobules should provide a
      foundation for improving the nutritional value and yield of plants.

PMID- 17499006
TI  - Response to Alpi et al.: Plant neurobiology--all metaphors have value.

PMID- 17499007
TI  - New insights into pectin methylesterase structure and function.
AB  - In bacteria, fungi and plants, pectin methylesterases are ubiquitous enzymes that
      modify the degree of methylesterification of pectins, which are major components
      of plant cell walls. Such changes in pectin structure are associated with changes
      in cellular adhesion, plasticity, pH and ionic contents of the cell wall and
      influence plant development and stress responses. In plants, pectin
      methylesterases belong to large multigene families, are regulated in a highly
      specific manner, and are involved in vegetative and reproductive processes,
      including wood and pollen formation, in addition to plant-pathogen interactions.
      Although, overall, protein structures are highly conserved between isoforms,
      recent data indicate that structural variations might be associated with the
      targeting and functions of specific pectin methylesterases.

PMID- 17499008
TI  - Will genomics guide a greener forest biotech?
AB  - Forest biotechnology has been increasingly associated with wood production using
      plantation forestry, and has stressed applications that use pedigreed material
      and transgenic trees. Reasons for this emphasis include limitations of available
      technologies to conform to underlying genetic features of undomesticated forest
      tree populations. More recently, genomic technologies have rapidly begun to
      expand the scope of forest biotechnology. Genomic technologies are well suited to
      describe and make use of the abundant genetic variation present in undomesticated
      forest tree populations. Genomics thus enables new research and applications for
      conservation and management of natural forests, and is a primary technological
      driver for new research addressing the use of forests trees for carbon
      sequestration, biofuels feedstocks, and other 'green' applications.

PMID- 17499009
TI  - Emergence of symmetry breaking in fucoid zygotes.
AB  - Fucoid zygotes are model cells for the study of symmetry breaking in plants.
      After fertilization, their initial spherical symmetry reduces to an axial
      symmetry, even in the absence of any external cue. This indicates that zygotes
      have an intrinsic ability to break symmetry in a way that is solely dependent on
      their internal biochemical and/or biophysical state. In our opinion, symmetry
      breaking is a self-organized process. It arises around the fucoid zygotes from
      the ion dynamics through channels (voltage-dependent calcium channels and a
      potassium leak) and outside the membrane (electrodiffusion owing to slower
      calcium diffusion compared with potassium). The robustness of this self-organized
      process and its lability ensure its relevance in plants where symmetry breaking
      is correlated with transcellular ion currents.

PMID- 17499010
TI  - Tear analysis and lens-tear interactions. Part I. Protein fingerprinting with
      microfluidic technology.
AB  - The purpose of this work is to establish the application of a fully automated
      microfluidic chip based protein separation assay in tear analysis. It is rapid,
      requires small sample volumes and is vastly superior to, and more convenient
      than, comparable conventional gel electrophoresis assays. The protein sizing chip
      technology was applied to three specific fields of analysis. Firstly tear samples
      were collected regularly from subjects establishing the baseline effects of tear
      stimulation, tear state and patient health. Secondly tear samples were taken from
      lens wearing eyes and thirdly the use of microfluidic technology was assessed as
      a means to investigate a novel area of tear analysis, which we have termed the
      'tear envelope'. Utilising the Agilent 2100 Bioanalyzer in combination with the
      Protein 200 Plus LabChip kit, these studies investigated tear proteins in the
      range of 14-200 kDa. Particular attention was paid to the relative concentrations
      of lysozyme, tear lipocalin, secretory IgA (sIgA), IgG and lactoferrin, together
      with the overall tear electropherogram 'fingerprint'. Furthermore, whilst lens
      tear interaction studies are generally thought of as an investigation into the
      effects of tears components on the contact lens material, i.e. deposition
      studies, this report addresses the reverse phenomenon--the effect of the lens,
      and particularly the newly inserted lens, on the tear fluid composition and
      dynamics. The use of microfluidic technology provides a significant advance in
      tear studies and should prove invaluable in tear diagnostics and contact lens
      performance analysis.

PMID- 17499011
TI  - High-throughput spectrophotometric assay of reactive oxygen species in serum.
AB  - The derivatives of reactive oxygen metabolites (D-ROM) test has been developed to
      determine the amount of oxygen-centered free radicals in a blood sample as a
      marker of oxidative stress. This study aims to improve the D-ROM test and develop
      an automated assay system by use of a clinical chemistry analyzer. Five
      microliters of serum was added to 1 well of a 96-well microtiter plate for a
      total 240microl of reaction solution containing alkylamine and metals. This was
      followed by automatic mixing, incubation and measurement of reactive oxygen
      species (ROS) levels as a color development at 505nm using a spectrophotometer
      with catalytic capability for transition metals. This assay system was used to
      measure serum levels of ROS in cigarette smokers and never-smokers, by way of
      example. The levels of serum ROS determined by this system correlate with the
      amounts of free radicals and peroxides, which reacted with various molecules in
      the body and formed stable metabolites. This test can use frozen sera as well as
      fresh ones. The inter- and intra-deviation of this system was within 5% and
      showed consistent linearity in the range between 4 and 500mg/l of hydrogen
      peroxides. Serum ROS levels among smokers increased with the number of cigarettes
      smoked per day (36.5% increment per pack per day; P<0.0001). This assay system
      will be a simple, inexpensive, and reliable tool for assessing oxidative stress
      in human populations. Our preliminary results on cigarette smoking imply that
      this assay system has potential for application in various epidemiological and
      clinical settings.

PMID- 17499012
TI  - Quantification of a potent mutagenic 4-amino-3,3'-dichloro-5,4'-dinitrobiphenyl
      (ADDB) and the related chemicals in water from the Waka River in Wakayama, Japan.
AB  - 4-Amino-3,3'-dichloro-5,4'-dinitrobiphenyl (ADDB) is a novel chemical exerting
      strong mutagenicity, especially in the absence of metabolic activation. In
      addition to mutagenicity, ADDB may also disrupt the endocrine system in vitro.
      ADDB may be discharged from chemical plants near the Waka River and could be
      unintentionally formed via post-emission modification of drainage water
      containing 3,3'-dichlorobenzidine (DCB), which is a precursor in the manufacture
      of polymers and dye intermediates in chemical plants. The main purpose of this
      study was to make a comprehensive survey of the behaviour and levels of ADDB and
      suspected starting material or intermediates of ADDB, i.e., DCB, 3,3'-dichloro
      4,4'-dinitrobiphenyl (DDB), and 4-amino-3,3'-dichloro-4'-nitrobipheny (ADNB) in
      Waka River water samples. We also postulated the formation pathway of ADDB. Water
      samples were collected at five sampling sites from the Waka River four times
      between March 2003 and December 2004. Samples were passed through Supelpak2
      columns, and adsorbed materials were then extracted with methanol. Extracts were
      used for quantification of ADDB and the related chemicals by HPLC on reverse
      phase columns; mutagenicity was evaluated in the Salmonella assay using the O
      acetyltransferase-overexpressing strain YG1024. High levels of ADDB, DCB, DDB,
      and ADNB (12.0, 20,400, 134.8, and 149.4ng/L-equivalent) were detected in the
      samples collected at the site where wastewater was discharged from chemical
      plants into the river. These water samples also showed stronger mutagenicity in
      YG1024 both with and without S9 mix than the other water samples collected from
      upstream and downstream sites. The results suggest that ADDB is unintentionally
      formed from DCB via ADNB in the process of wastewater treatment of drainage water
      containing DCB from chemical plants.

PMID- 17499013
TI  - Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte
      oxidative DNA damage in rats.
AB  - Doxorubicin (DOX) is an efficient chemotherapeutic agent used against several
      types of tumors; however, its use is limited due to severe cardiotoxicity. Since
      it is accepted that reactive oxygen species are involved in DOX-induced
      cardiotoxicity, antioxidant agents have been used to attenuate its side effects.
      To determine tomato-oleoresin protection against cardiac oxidative DNA damage
      induced by DOX, we distributed Wistar male rats in control (C), lycopene (L), DOX
      (D) and DOX+lycopene (DL) groups. They received corn oil (C, D) or tomato
      oleoresin (5mg/kg body wt. day) (L, DL) by gavage for a 7-week period. They also
      received saline (C, L) or DOX (4mg/kg body wt.) (D, DL) intraperitoneally at the
      3rd, 4th, 5th, and at 6th week. Lycopene absorption was checked by HPLC. Cardiac
      oxidative DNA damage was evaluated by the alkaline Comet assay using
      formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (endo III).
      Cardiomyocyte levels of SBs, SBs FPG and SBs Endo III were higher in rats from D
      when compared to other groups. DNA damage levels in cardiomyocytes from DL were
      not different when compared to C and L groups. The viability of cardiomyocytes
      from D or DL was lower than C or L groups (p<0.01). Lycopene levels (mean+/
      S.D.nmol/kg) in saponified hearts were similar between L (47.43+/-11.78) and DL
      (49.85+/-16.24) groups. Our results showed: (1) lycopene absorption was confirmed
      by its cardiac levels; (2) DOX-induced oxidative DNA damage in cardiomyocyte; (3)
      tomato-oleoresin supplementation protected against cardiomyocyte oxidative DNA
      damage.

PMID- 17499014
TI  - Genotoxicity of 15-deoxygoyazensolide in bacteria and yeast.
AB  - Sesquiterpene lactones (SLs) present a wide range of pharmacological activities.
      The aim of our study was to investigate the genotoxicity of 15-deoxygoyazensolide
      using the Salmonella/microsome assay and the yeast Saccharomyces cerevisiae. We
      also investigated the nature of induced DNA damage using yeast strains defective
      in DNA repair pathways, such as nucleotide excision repair (RAD3), error prone
      repair (RAD6), and recombinational repair (RAD52), and in DNA metabolism, such as
      topoisomerase mutants. 15-deoxygoyasenzolide was not mutagenic in Salmonella
      typhimurium, but it was mutagenic in S. cerevisiae. The hypersensitivity of the
      rad52 mutant suggests that recombinational repair is critical for processing
      lesions resulting from 15-deoxygoyazensolide-induced DNA damage, whereas excision
      repair and mutagenic systems does not appear to be primarily involved. Top 1
      defective yeast strain was highly sensitive to the cytotoxic activity of 15
      deoxygoyazensolide, suggesting a possible involvement of this enzyme in the
      reversion of the putative complex formation between DNA and this SL, possibly due
      to intercalation. Moreover, the treatment with this lactone caused dose-dependent
      glutathione depletion, generating pro-oxidant status which facilitates oxidative
      DNA damage, particularly DNA breaks repaired by the recombinational system ruled
      by RAD52 in yeast. Consistent with this finding, the absence of Top1 directly
      affects chromatin remodeling, allowing repair factors to access oxidative damage,
      which explains the high sensitivity to top1 strain. In summary, the present study
      shows that 15-deoxygoyazensolide is mutagenic in yeast due to the possible
      intercalation effect, in addition to the pro-oxidant status that exacerbates
      oxidative DNA damage.

PMID- 17499015
TI  - The activities of mycotoxins derived from Fusarium and related substances in a
      short-term transformation assay using v-Ha-ras-transfected BALB/3T3 cells (Bhas
      42 cells).
AB  - Cell transformation assays using BALB/3T3 cells can mimic the two-stage process
      of chemical carcinogenesis in experimental animals. A short-term transformation
      assay using v-Ha-ras-transfected BALB/3T3 cells (Bhas 42 cells), which was
      developed by Ohmori et al. and modified by Asada et al., has been reported to
      detect both tumor initiators and promoters as transformation initiators and
      promoters, respectively, with their differences based on their protocols. In this
      new short-term assay, we examined mycotoxins derived from Fusarium and related
      substances for the initiation and promotion activities of the transformation. The
      tested substances included deoxynivalenol, nivalenol, fusarenon-X, T-2 toxin,
      fumonisin B(1), fumonisin B(2), zearalenone, alpha-zearalanol, beta-zearalanol,
      alpha-zearalenol and beta-zearalenol. Fumonisin B(1) and T-2 toxin were positive
      for promoting activity in the assay. Especially, T-2 toxin was active at
      concentrations as low as 0.001-0.002microg/mL in the culture medium. From a
      comparison between the results of this study and published carcinogenicity assay
      data, it was expected that the Bhas 42 cell transformation assay had a good
      correlation with the two-stage carcinogenicity tests using experimental animals
      for estimation of the tumor-promoting activity.

PMID- 17499016
TI  - Complete sequence of the mitochondrial genome of Taenia saginata: comparison with
      T. solium and T. asiatica.
AB  - The complete sequence of the Taenia saginata mitochondrial genome was determined,
      and its organization and structure were compared to other human-tropic Taenia
      tapeworms for which complete mitochondrial sequence data were available. The
      mitochondrial genome was 13,670 bp long, contained 12 protein-coding genes, two
      ribosomal RNAs (rRNAs, a small and a large subunit), and 22 transfer RNAs
      (tRNAs). It did not encode the atp8 gene. Overlapping regions were found between
      nad4L and nad4, nad1 and trnN, and cox1 and trnT. The ATG initiation codon was
      used for 10 protein-coding genes, and the GTG initiation codon was used for the
      remaining 2 genes (nad4 and atp6). The size of the protein-coding genes of the
      three human Taenia tapeworms did not vary, except for Taenia solium nad1 (891 aa)
      and nad4 (1212 aa) and Taenia asiatica cox2 (576 aa). The tRNA genes were 57-75
      bp long, and the predicted secondary structures of 18 of these genes had typical
      clover-leaf shapes with paired dihydrouridine (DHU) arms. The genes in all human
      Taenia tapeworms for the two mitochondrial rRNA subunits rrnL and rrnS are
      separated by trnC. The putative T. saginata rrnL and rrnS are 972 and 732 bp
      long, respectively. The non-coding regions of the mt genome of T. saginata
      consisted of 2 regions: a short non-coding region (SNR, 66 nucleotides) and a
      long non-coding region (LNR, 159 nucleotides). The overall sequence difference in
      the full mitochondrial genome between T. saginata and T. asiatica was 4.6%, while
      T. solium differed by 11%. In conclusion, the complete sequence of the T.
      saginata mitochondrial genome will serve as a resource for comparative
      mitochondrial genomics and systematic studies of the parasitic cestodes.

PMID- 17499017
TI  - Synthesis and characterization of polyketanils with 3,8-diamino-6
      phenylphenanthridine moieties exhibiting light emitting properties molecular and
      supramolecular engineering concept.
AB  - Relationship between structures and properties of new conjugated polyketanils
      (PKs) with special architectures, synthesized from three diketones, i.e. p
      dibenzoylbenzene, dibenzyl, trans-1,2-dibenzoylethylene and 3,8-diamino-6
      phenylphenanthridine, was investigated. The photoluminescence (PL) of green,
      yellow and red emitting light polymers and their blend was studied. These
      included the effects of excitation wavelength, concentration and film thickness
      on the PL. Photoluminescence properties of the PKs before and after protonation
      with 10-Camphorsulfonic acid (CSA) were tested. The structure formation of
      (PKs)(1)(CSA)(2) complexes are discussed on the basis of FTIR spectroscopy.

PMID- 17499018
TI  - Photoluminescence of a mixed Langmuir-Blodgett film of C(60) and stearic acid at
      room temperature.
AB  - pi-A isotherms, transmission electron microscope (TEM), atomic force microscope
      (AFM) images and photoluminescence spectra of a mixed Langmuir-Blodgett (LB) film
      of C(60) and stearic acid (SA) deposited on silicon substrate have been measured
      at room temperature. C(60)/SA nanoparticles aggregated and formed an ordered net
      like structure when deposited on silicon substrate. Two PL intense bands centered
      at 731 and 806nm, respectively, which are rare at room temperature, were
      obtained. It is supposed that the particular ordered net-like construction of the
      LB film plays a crucial role in the enhancement of the photoluminescence. The
      731nm PL band is related with the aggregation state of the particles and the
      806nm PL band is referred as the intrinsic PL spectrum of the C(60).

PMID- 17499019
TI  - Enterovirus in arteriosclerosis: a pilot study.
AB  - BACKGROUND: Various pathogens have been suspected to play a role in the
      initiation or amplification of the atherosclerotic lesions. Both experimental and
      epidemiological arguments plead for a possible role of enterovirus in this
      process. OBJECTIVE: To determine the prevalence of enterovirus genome in
      atherosclerotic plaques, in comparison with Chlamydia pneumoniae, human
      cytomegalovirus (hCMV) and herpes simplex virus. STUDY DESIGN: Pilot study on 18
      patients who underwent artery resection. Five artery samples were tested for each
      patient and each pathogen by using PCR techniques whose sensitivity was evaluated
      for this kind of specimen. The quality of the extraction step was assessed by
      amplification of a fragment of the human aldolase A gene. RESULTS: The genome of
      at least one infectious agent was detected in artery samples from 7 of the 18
      patients (38.9%). In all cases, only one of the five aliquots was found positive;
      a confirmation was done by sequencing the PCR product. With regards to
      enterovirus, four patients (22.2%) were detected positive (one of them being also
      positive for hCMV). CONCLUSIONS: These results suggest that small amounts of
      enterovirus genome are commonly found in lesions of patients with advanced
      arteriosclerosis. Further studies are needed to evaluate the clinical
      significance of this association.

PMID- 17499020
TI  - Hypothesis: central nervous system delivery of cyclosporine A for therapy of
      progressive multifocal leukoencephalopathy.

PMID- 17499022
TI  - Morphological and molecular diversity of the monocercomonadid genera
      Monocercomonas, Hexamastix, and Honigbergiella gen. nov.
AB  - The family Monocercomonadidae (Parabasala, Trichomonadida) is characterized by
      the absence of a costa and in most species also of an undulating membrane; both
      of which are typical structures of trichomonadids. We have examined 25 isolates
      of Monocercomonadidae species by sequencing of the SSU rDNA and the ITS region
      and by light and transmission electron microscopy. The isolates formed three
      distinct phylogenetically unrelated clades: (1) Monocercomonas colubrorum, (2)
      Monocercomonas ruminantium together with a strain ATCC 50321 designated as
      Pseudotrichomonas keilini, and (3) Hexamastix. Twenty isolates of Monocercomonas
      colubrorum split into three clades with no host-specificity. The morphological
      differences among clades were insufficient to classify them as a separate
      species. Non-monophyly of the cattle commensal Monocercomonas ruminantium with
      the type species Monocercomonas colubrorum and absence of Pseudotrichomonas
      characters in the free-living strain ATCC 50321 led to their reclassification
      into a new genus (Honigbergiella gen. nov.). The close relationship of these
      strains indicates a recent switch between a free-living habit and endobiosis. Two
      strains of Hexamastix represented different species -Hexamastix kirbyi Honigberg
      1955 and Hexamastix mitis sp. nov. Polyphyly of the Monocercomonadidae confirmed
      that the absence of a costa and an undulating membrane are not taxonomically
      significant characters and were probably secondarily lost in some or all clades.
      Our observations, however, indicated that other characters - infrakinetosomal
      body, comb-like structure, marginal lamella, and the type of axostyle - are fully
      consistent with the position of Monocercomonadidae species in the parabasalian
      tree and are, therefore, reasonable taxonomic characters.

PMID- 17499021
TI  - Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2.
AB  - Phosphatidylcholine transfer protein (PC-TP) is a highly specific soluble lipid
      binding protein that transfers phosphatidylcholine between membranes in vitro. PC
      TP is a member of the steroidogenic acute regulatory protein-related transfer
      (START) domain superfamily. Although its biochemical properties and structure are
      well characterized, the functions of PC-TP in vivo remain incompletely
      understood. Studies of mice with homozygous disruption of the Pctp gene have
      largely refuted the hypothesis that this protein participates in the
      hepatocellular selection and transport of biliary phospholipids, in the
      production of lung surfactant, in leukotriene biosynthesis and in cellular
      phosphatidylcholine metabolism. Nevertheless, Pctp(-/-) mice exhibit interesting
      defects in lipid homeostasis, the understanding of which should elucidate the
      biological functions of PC-TP.

PMID- 17499023
TI  - Neuromuscular fatigue following constant versus variable-intensity endurance
      cycling in triathletes.
AB  - The aim of this study was to determine whether or not variable power cycling
      produced greater neuromuscular fatigue of knee extensor muscles than constant
      power cycling at the same mean power output. Eight male triathletes (age: 33+/-5
      years, mass: 74+/-4 kg, VO2max: 62+/-5 mL kg(-1) min(-1), maximal aerobic power:
      392+/-17 W) performed two 30 min trials on a cycle ergometer in a random order.
      Cycling exercise was performed either at a constant power output (CP)
      corresponding to 75% of the maximal aerobic power (MAP) or a variable power
      output (VP) with alternating +/-15%, +/-5%, and +/-10% of 75% MAP approximately
      every 5 min. Maximal voluntary contraction (MVC) torque, maximal voluntary
      activation level and excitation-contraction coupling process of knee extensor
      muscles were evaluated before and immediately after the exercise using the
      technique of electrically evoked contractions (single and paired stimulations).
      Oxygen uptake, ventilation and heart rate were also measured at regular intervals
      during the exercise. Averaged metabolic variables were not significantly
      different between the two conditions. Similarly, reductions in MVC torque
      (approximately -11%, P<0.05) after cycling were not different (P>0.05) between CP
      and VP trials. The magnitude of central and peripheral fatigue was also similar
      at the end of the two cycling exercises. It is concluded that, following 30 min
      of endurance cycling, semi-elite triathletes experienced no additional
      neuromuscular fatigue by varying power (from +/-5% to 15%) compared with a
      protocol that involved a constant power.

PMID- 17499024
TI  - The malaria parasite type II NADH:quinone oxidoreductase: an alternative enzyme
      for an alternative lifestyle.
AB  - The operation of a type II NADH:quinone oxidoreductase (PfNDH2), also known as
      alternative Complex I, in the mitochondrion of the human malaria parasite,
      Plasmodium falciparum, has recently been described. Unlike the Complex I of
      typical mitochondria, type II NADH:quinone oxidoreductases do not have
      transmembrane domains and are not involved directly in proton (H(+)) pumping.
      Here, we present a predictive model of PfNDH2, describing putative NADH-, flavin-
      and quinone-binding sites, as well as a possible membrane 'anchoring' region. In
      addition, we hypothesize that the alternative Complex I is an evolutionary
      adaptation to a microaerophilic lifestyle enabling (proton) uncoupled oxidation
      of NADH. This adaptive feature has several advantages, including: (i) a reduction
      of proton 'back-pressure' in the absence of extensive ATP synthesis; (ii) a
      reduction of mitochondrial superoxide generation; and (iii) a mechanism for the
      deregulated oxidation of cytosolic NADH.

PMID- 17499025
TI  - Reliability and validity of a Chinese version of the Quality of Life in Epilepsy
      Inventory (QOLIE-89).
AB  - OBJECTIVE: The aim of the work described here was to develop and validate a
      Chinese version of the Quality of Life in Epilepsy Inventory-89 (QOLIE-89).
      METHODS: The original English version of the QOLIE-89 was adapted to the Chinese
      language through a translation-retranslation procedure. The inventory was then
      completed by 293 adult patients with epilepsy. Forty patients also completed the
      Chinese version of the QOLIE-31. Test-retest and internal consistency
      reliabilities, criterion validity, and discriminative validity were assessed.
      RESULTS: Test-retest reliability (Pearson's correlation coefficient) for the
      Chinese version of the QOLIE-89 ranged from 0.70 to 0.98, and internal
      consistency reliability (Cronbach's alpha) ranged from 0.70 to 0.99. Spearman's
      rank correlation between the total scores on the Chinese versions of the QOLIE-89
      and QOLIE-31 was 0.97, and domain scores ranged from 0.86 to 1.00. QOLIE-89 items
      could be used to discriminate between patients with respect to epileptic seizure
      severity and antiepileptic drug side effects. CONCLUSION: The psychometric
      properties of the Chinese version of the QOLIE-89 are good and similar to those
      of the American version and can be applied to assess quality of life in adult
      patients with epilepsy in China.

PMID- 17499026
TI  - Constructing the gene regulation-level representation of microarray data for
      cancer classification.
AB  - In this paper, we propose a regulation-level representation for microarray data
      and optimize it using genetic algorithms (GAs) for cancer classification.
      Compared with the traditional expression-level features, this representation can
      greatly reduce the dimensionality of microarray data and accommodate noise and
      variability such that many statistical machine-learning methods now become
      applicable and efficient for cancer classification. Experimental results on real
      world microarray datasets show that the regulation-level representation can
      consistently converge at a solution with three regulation levels. This verifies
      the existence of the three regulation levels (up-regulation, down-regulation and
      non-significant regulation) associated with a particular biological phenotype.
      The ternary regulation-level representation not only improves the cancer
      classification capability but also facilitates the visualization of microarray
      data.

PMID- 17499027
TI  - Rational sub-division of plant trypanosomes (Phytomonas spp.) based on minicircle
      conserved region analysis.
AB  - The sequences of minicircle conserved regions from various plant trypanosomatids
      have been determined and analyzed. The goal of this study was to add another tool
      to the arsenal of molecular probes for distinguishing between the different
      trypanosomatids occurring in plants: systemic trypanosomatids multiplying in the
      sap, those from the laticiferous tubes, and those developing in fruits, seeds or
      flowers but not in the plant itself and that are frequently considered as
      opportunistic insect trypanosomatids. As some plant intraphloemic trypanosomatids
      are the causative agents of important diseases, a clear definition of the
      different types of trypanosomatids is critical. The conserved region of the
      mitochondrial minicircle provides several specific features in a small sequence
      region containing three functionally elements required for minicircle
      replication. Trees generated from the analysis recapitulated trees drawn from
      analyses of isoenzymes, RAPD, and particular gene sequences, supporting the
      validity of the small region used in this work. Three groups of isolates were
      significant and in accordance with previous work. The peculiarity of phloem
      restricted trypanosomatids associated with wilts of coconut and oil palm in Latin
      America - group H - is confirmed. In agreement with previous studies on their
      biological and serological properties the results highlighted this group called
      'phloemicola'. It always differentiated from all other latex and fruit isolates
      or opportunistic trypanosomatids, like insect trypanosomatids. We can assert that
      phloemicola is the only well-defined taxon among all plant trypanosomatids. A
      group of non-pathogenic latex isolates from South American euphorbs (G), and a
      heterogenous group (A) including one fruit, one possible latex and one insect
      isolate are clearly distinct groups. The group of Mediterranean isolates from
      latex (D), even with a low boostrap, stood out well from other groups. The
      remainder of the isolates fell into a heterogeneous cluster. At least eight
      different groups in the plant trypanosomatids were identified.

PMID- 17499028
TI  - Intra- and intergenotype characterization of D6 measles virus genotype.
AB  - Determination of inter- and intragenotype stability and variability are the basic
      tools for the molecular epidemiology and evolutionary investigation of measles
      virus (MV). We made a comparison between complete genome sequences of four MVs
      (two wt MV strains-WA.USA/17.98 and 97-45881, and two SSPE MV strains
      MVs/Zagreb.CRO/47.02/and MVs/Zagreb.CRO/08.03/), all belonging to genotype D6.
      Results of analyses clearly confirm that MV genome continuously changes within
      the viruses of the same or different genotypes by accumulation of mutations in
      different parts of the genome. Only a small number of these accumulated mutations
      induce amino acid substitutions and thus possibly introduce new biological
      characteristics or a new genotype over a long time period. This study clearly
      reveals a long untranslated region between M and F genes as the most variable
      region of the MV genome and detects the presence of unique residues on the level
      of the entire genome as a new important parameter in the investigation of
      molecular evolution of MVs.

PMID- 17499029
TI  - On translocation mechanism of ring-shaped helicase along single-stranded DNA.
AB  - The ring-shaped helicases represent one important group of helicases that can
      translocate along single-stranded (ss) DNA and unwinding double-stranded (ds) DNA
      by using the energy derived from NTP binding and hydrolysis. Despite intensive
      studies, the mechanism by which the ring-shaped helicase translocates along ssDNA
      and unwinds dsDNA remains undetermined. In order to understand their
      chemomechanical-coupling mechanism, two models on NTPase activities of the
      hexamers in the presence of DNA have been studied here. One model is assumed
      that, of the six nucleotide-binding sites, three are noncatalytic and three are
      catalytic. The other model is assumed that all the six nucleotide-binding sites
      are catalytic. In terms of the sequential NTPase activity around the ring and the
      previous determined crystal structure of bacteriophage T7 helicase it is shown
      that the obtained mechanical behaviors such as the ssDNA-translocation size and
      DNA-unwinding size per dTTPase cycle using the former model are in good
      quantitative agreement with the previous experimental results for T7 helicase.
      Moreover, the acceleration of DNA unwinding rate with the stimulation of DNA
      synthesis by DNA polymerase can also be well explained by using the former model.
      In contrast, the ssDNA-translocation size and DNA-unwinding size per dTTPase
      cycle obtained by using the latter model are not consistent with the experimental
      results for T7 helicase. Thus it is preferred that the former model is the
      appropriate one for the T7 helicase. Furthermore, using the former model some
      dynamic behaviors such as the rotational speeds of DNA relative to the T7
      helicase when translocation along ssDNA and when unwinding dsDNA have been
      predicted, which are expected to test in order to further verify the model.

PMID- 17499030
TI  - Remarkable enhancement in PLD activity from Streptoverticillium cinnamoneum by
      substituting serine residue into the GG/GS motif.
AB  - The gene that encodes phospholipase D (PLD) from Streptoverticillium cinnamoneum
      contains three consensus regions (Region I, II and IV as shown in Fig. 1A) that
      are conserved among the PLD superfamily. The glycine-glycine (GG) motif in Region
      I and the glycine-serine (GS) motif in Region IV are also conserved in the PLD
      superfamily. These (GG and GS) motifs are located 7 residues downstream from each
      HKD motif. In an investigation of fifteen GG/GS motif mutants, generated as
      fusion proteins with maltose-binding protein (MBP-PLDs), three highly active
      mutants were identified. Three of the mutants (G215S, G216S, and G216S-S489G)
      contained a serine residue in the GG motif, and exhibited approximately a 9-27
      fold increased transphosphatidylation activity to DPPC compared with recombinant
      wild type MBP-PLD. When heat stability was compared between three mutants and the
      recombinant wild type, only G216S-S489G showed heat labile properties. It appears
      that the 489th serine residue in the GS motif also contributes to the thermal
      stability of the enzyme. In addition, the GG/GS motif was very close to the
      active center residue, including two HKD motifs, as shown by computer modeling.
      The findings suggest that the GG/GS motif of PLD is a key motif that affects
      catalytic function and enzymatic stability.

PMID- 17499031
TI  - Peptide binding specificity of the chaperone calreticulin.
AB  - Calreticulin is a molecular chaperone with specificity for polypeptides and N
      linked monoglucosylated glycans. In order to determine the specificity of
      polypeptide binding, the interaction of calreticulin with polypeptides was
      investigated using synthetic peptides of different length and composition. A
      large set of available synthetic peptides (n=127) was tested for binding to
      calreticulin and the results analysed by multivariate data analysis. The
      parameter that correlated best with binding was hydrophobicity while beta-turn
      potential disfavoured binding. Only hydrophobic peptides longer than 5 amino
      acids showed binding and a clear correlation with hydrophobicity was demonstrated
      for oligomers of different hydrophobic amino acids. Insertion of hydrophilic
      amino acids in a hydrophobic sequence diminished or abolished binding. In
      conclusion our results show that calreticulin has a peptide-binding specificity
      for hydrophobic sequences and delineate the fine specificity of calreticulin for
      hydrophobic amino acid residues.

PMID- 17499032
TI  - Real-time monitoring of moisture levels in wound dressings in vitro: an
      experimental study.
AB  - Retaining an appropriate level of moisture at the interface between a healing
      wound and an applied dressing is considered to be critical for effective wound
      healing. Failure to control exudate at this interface can result in maceration or
      drying out of the wound surface. The ability to control moisture balance at the
      wound interface is therefore a key aspect of wound dressing performance. To date
      it has not been possible to monitor in any effective manner the distribution of
      moisture within dressings or how this varies with time. A new measurement system
      is presented based on sensors placed at the wound/dressing interface which are
      capable of monitoring moisture levels in real time. The system comprises a model
      wound bed and sensor array complete with fluid injection path to mimic exudate
      flow. Eight monitoring points, situated beneath the test dressing, allow the
      moisture profile across the complete dressing to be measured both during and
      after fluid injection. The system has been used to evaluate the performance of
      four foam dressings, a composite hydrofibre dressing and a film dressing. Stark
      contrasts in the performance of the wound contact layer were found between the
      different wound dressing types. The composite hydrofibre dressing retained
      moisture at the wound interface throughout the experiments while areas of the
      foam dressing quickly became dry, even during constant injection of fluid. The
      abundance of sensors allowed a moisture map of the surface of the wound dressing
      to be constructed, illustrating that the moisture profile was not uniform across
      several of the dressings tested during absorption and evaporation of liquid.
      These results raise questions as to how the dressings behave on a wound in vivo
      and indicate the need for a similar clinical monitoring system for tracking wound
      moisture levels.

PMID- 17499033
TI  - Gastric duplication cyst mimicking a pancreatic pseudocyst in a patient with
      chronic pancreatitis.

PMID- 17499034
TI  - Combined use of free vascularised bone graft and extracorporeally-irradiated
      autograft for the reconstruction of massive bone defects after resection of
      malignant tumour.
AB  - We review eight patients who underwent curative resection for malignant
      musculoskeletal tumour followed by reconstruction with vascularised bone graft in
      combination with extracorporeally-irradiated autograft. This method consists of
      (1) wide en-bloc resection of the tumour; (2) curettage of tumour from the
      resected bone; (3) extracorporeal irradiation with 60 to 70 Gy as a bolus single
      dose; (4) vascularised bone grafting from the fibula (six cases) or scapula (two
      cases); (5) re-implantation of the irradiated bone into the recipient and
      fixation with plates and screws. Five cases were located in the tibial shaft and
      one each in the ulnar shaft, distal femur and acetabulum. Radiological and
      functional outcomes were excellent in four patients who were reconstructed with
      vascularised fibula and irradiated intercalary tibial bone graft. Two patients
      with irradiated osteochondral graft showed osteoarthritic change in the long
      term. No local recurrences arising from the irradiated bones were detected.
      Combination of a vascularised and an extracorporeally-irradiated bone graft is a
      useful reconstructive tool for massive bone defects arising from resection of
      malignant musculoskeletal tumour. This approach has the advantage of combining
      the biological properties provided by the vascularised bone graft with the
      mechanical endurance of the irradiated bone autograft. The method is best
      indicated for intercalary defects of the tibia.

PMID- 17499035
TI  - Triamcinolone reduces seroma re-accumulation in the extended latissimus dorsi
      donor site.
AB  - BACKGROUND: The incidence of donor site seroma after autologous latissimus dorsi
      (ALD) breast reconstruction is in the order of 70%. In the majority of cases the
      seroma recurs following an initial aspiration. We designed a double-blind
      randomised controlled trial to test the hypothesis that an intracavity injection
      of the anti-inflammatory corticosteroid triamcinolone would inhibit seroma re
      accumulation. METHODS: We recruited 52 ALD breast reconstructions in 49 patients,
      of whom 41 involved immediate reconstruction and 11 delayed reconstruction.
      Patients exhibiting seromas at their first postoperative visit were randomised to
      receive either intracavity triamcinolone 80 mg (Group A, n=29) or saline (Group
      B, n=23), following seroma aspiration. We recorded the incidence of wound
      complications, total time (days) and number/volume of subsequent aspirations to
      dryness. RESULTS: Triamcinolone significantly reduced the need for any further
      aspiration (A=16/29, B=22/23), total number of aspirations (A: median=1,
      interquartile range=0-1; B: median=4, interquartile range=2-5; P<0.0001), total
      volume aspirated (A: median=30 ml, interquartile range=0-80; B: median=325 ml,
      interquartile range=199-550; P<0.0001), and total time to dryness (A: median=12
      days, interquartile range 7-17; B: median=37 days, interquartile range 20-49;
      P<0.0001). The incidence of adjuvant chemotherapy (A=16/29, B=9/23) and
      radiotherapy (A=16/29, B=10/23) was similar, and there was no effect upon donor
      site complications (Group A=4/29, Group B=2/23, P=0.725). The mean follow-up time
      for patients in the steroid group was 264 days compared to 254 days for those in
      the placebo group. Steroid injections were well tolerated, and there were no
      infective complications. CONCLUSION: Following initial aspiration, intracavity
      injection of triamcinolone significantly reduced seroma re-accumulation after ALD
      breast reconstruction.

PMID- 17499036
TI  - The pedicled vascularised scapular bone flap for proximal humerus reconstruction
      and short humeral stump lengthening.
AB  - The vascularised scapular bone free flap is popular in mandible reconstruction,
      but it is less commonly used as a pedicled flap to reconstruct the upper humerus.
      We analysed our experience with pedicled scapular crest flaps in humerus
      reconstruction and compared our results with cases reported in the literature. We
      considered the age at surgery, the time elapsed before reconstruction, the time
      required to obtain solid bony union, the operative indication, the osteosynthesis
      procedure used and whether circumflex scapular vessels or angular vessels were
      used. There were eight patients (seven men and one woman, mean age=33): four
      humerus stump lengthenings, two upper-third humerus bone and soft tissue defects
      and two multioperated established humerus non-unions. Flaps were pedicled either
      on circumflex scapular vessels (three) or angular vessels (five). The mean size
      of the scapular bone used was 9.4 cm (range 7-11 cm). We associated a covering
      flap for seven patients. All the flaps survived and bone healed in a 3.75 month
      mean delay (range three to six months), and there was one accidental secondary
      fracture one year after reconstruction. For a vascularised reconstruction of the
      upper humerus, the pedicled scapular bone flap is a valuable option especially if
      a composite reconstruction is needed. For short humerus stump lengthening, this
      flap seems to provide a very satisfactory solution.

PMID- 17499037
TI  - Bachelor of Midwifery: reflections on the first 5 years from two Victorian
      universities.
AB  - Bachelor of Midwifery programs in the state of Victoria, Australia commenced in
      2002 through an affiliation of three universities in Melbourne named the 'Werna
      Naloo Bachelor of Midwifery consortium'. The approach allowed for collaborative
      synergies in program delivery through offering online 'consortium' units each
      semester in addition to on-campus content at each university. It is now 5 years
      since the first cohort of students commenced the course. During those years,
      members of the consortium have experienced a range of challenges and tensions.
      This paper provides a reflection by the course coordinators from two remaining
      members of the consortium, Australian Catholic University and Monash University.
      It explores issues confronted, regulation and registration, educational and
      clinical practice issues. In addition, the authors discuss course outcomes in
      terms of employment of graduates and their integration into the workforce, career
      development pathways and demand for the course. The authors conclude that the
      consortium has been successful and course outcomes positive with graduates
      successful in securing employment. Overall, the future for the Bachelor of
      Midwifery at both universities appears positive.

PMID- 17499038
TI  - Transmenopausal changes in the trabecular bone structure.
AB  - INTRODUCTION: Post-menopausal osteoporosis is a disorder of excess skeletal
      fragility, due partly to changes in bone microstructure. Menopause is known to
      result in bone loss and reduction in bone mechanical strength. However, the
      mechanism and nature of microstructural changes at menopause need more detailed
      description and analyses. The overall hypothesis for this analysis is that the
      variables describing trabecular bone micro-architecture will be affected by
      changes in the hormonal status of women just prior to, and early after, last
      menses, and that volumetric bone density, and trabecular structure will decline
      significantly. The study was designed to capture true longitudinal
      transmenopausal changes in three-dimensional (3-D) trabecular bone architecture.
      Currently, minimal data exist regarding these features. MATERIALS AND METHODS:
      Transilial biopsies specimens were obtained from healthy pre-menopausal women
      (age >46), and repeated at 12 months after the last menstrual period. Bone
      architecture was quantified in 38 paired specimens using micro-computed
      tomography (micro-CT-40, Scanco) techniques. Bone biopsies were embedded for
      histomorphomteric analyses and parts of the analyses have been published
      elsewhere. Embedded bone biopsies were scanned at 30-mum resolution such that the
      region of interest was similar to that in the two-dimensional (2-D)
      histomorphometric analyses. Paired t-tests were used to compare the pre- and post
      menopausal bone structural data from each technique. RESULTS: There was good
      correlation between standard histomorphometric (2-D) and micro-CT (3-D)
      measurements. Most of the variables characterizing bone structure in post
      menopausal women (from micro-CT) significantly decreased (BV/TV, trabecular
      number, apparent and tissue density). In addition, both trabecular spacing (Tb.S)
      and the structure model index (SMI) increased in the post-menopausal women
      suggesting transformation of trabecular bone from plate- to rod-like structure.
      The 3-D trabecular connectivity density (Conn.D) was negatively correlated with
      activation frequency (Ac.f). CONCLUSIONS: These data suggest that 3-D micro-CT
      measurements (longitudinal) are comparable to those of standard histomorphometry,
      and that most of the bone structural measurements are sensitive to changes in
      women's hormonal status across menopause.

PMID- 17499039
TI  - The ribosomal peptidyl transferase.
AB  - Peptide bond formation on the ribosome takes place in an active site composed of
      RNA. Recent progress of structural, biochemical, and computational approaches has
      provided a fairly detailed picture of the catalytic mechanism of the reaction.
      The ribosome accelerates peptide bond formation by lowering the activation
      entropy of the reaction due to positioning the two substrates, ordering water in
      the active site, and providing an electrostatic network that stabilizes the
      reaction intermediates. Proton transfer during the reaction appears to be
      promoted by a concerted proton shuttle mechanism that involves ribose hydroxyl
      groups on the tRNA substrate.

PMID- 17499040
TI  - A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA
      ends.
AB  - The mechanisms by which telomeres are distinguished from DNA double-strand breaks
      are poorly understood. Here we have defined the minimal requirements for the
      protection of telomeric DNA ends from nonhomologous end-joining (NHEJ). Neither
      long, single-stranded overhangs nor t loop formation is essential to prevent NHEJ
      mediated ligation of telomeric ends in vitro. Instead, a tandem array of 12
      telomeric repeats is sufficient to impede illegitimate repair in a highly
      directional manner at nearby DNA ends. The polarity of end protection is
      consistent with the orientation of naturally occurring telomeres and is well
      suited to minimize interference between chromosome capping and the repair of DNA
      double-strand breaks in subtelomeric sequences. Biochemical fractionation and
      reconstitution revealed that telomere protection is mediated by a RAP1/TRF2
      complex, providing evidence for a direct role for human RAP1 in the protection of
      telomeric DNA from NHEJ.

PMID- 17499041
TI  - A nonuniform stepping mechanism for E. coli UvrD monomer translocation along
      single-stranded DNA.
AB  - E. coli UvrD is an SF1 helicase involved in several DNA metabolic processes.
      Although a UvrD dimer is needed for helicase activity, a monomer can translocate
      with 3' to 5' directionality along single-stranded DNA, and this ATP-dependent
      translocation is likely involved in RecA displacement. In order to understand how
      the monomeric translocase functions, we have combined fluorescence stopped-flow
      kinetic methods with recently developed analysis methods to determine the kinetic
      mechanism, including ATP coupling stoichiometry, for UvrD monomer translocation
      along ssDNA. Our results suggest that the macroscopic rate of UvrD monomer
      translocation is not limited by each ATPase cycle but rather by a slow step
      (pause) in each translocation cycle that occurs after four to five rapid 1 nt
      translocation steps, with each rapid step coupled to hydrolysis of one ATP. These
      results suggest a nonuniform stepping mechanism that differs from either a
      Brownian motor or previous structure-based inchworm mechanisms.

PMID- 17499042
TI  - NELF interacts with CBC and participates in 3' end processing of replication
      dependent histone mRNAs.
AB  - Negative elongation factor (NELF) is a four subunit transcription elongation
      factor that has been implicated in numerous diseases ranging from neurological
      disorders to cancer. Here we show that NELF interacts with the nuclear cap
      binding complex (CBC), a multifunctional factor that plays important roles in
      several mRNA processing steps, and the two factors together participate in the 3'
      end processing of replication-dependent histone mRNAs, most likely through
      association with the histone stem-loop binding protein (SLBP). Strikingly,
      absence of NELF and CBC causes aberrant production of polyadenylated histone
      mRNAs. Moreover, NELF is physically associated with histone gene loci and forms
      distinct intranuclear foci that we call NELF bodies, which often overlap with
      Cajal bodies and cleavage bodies. Our results point to a surprising role of NELF
      in the 3' end processing of histone mRNAs and also suggest that NELF is a new
      factor that coordinates different mRNA processing steps during transcription.

PMID- 17499043
TI  - Mammalian Maf1 is a negative regulator of transcription by all three nuclear RNA
      polymerases.
AB  - Most eukaryotic transcriptional regulators act in an RNA polymerase (Pol)
      selective manner. Here we show that the human Maf1 protein negatively regulates
      transcription by all three nuclear Pols. Changes in Maf1 expression affect Pol I-
      and Pol III-dependent transcription in human glioblastoma lines. These effects
      are mediated, in part, through the ability of Maf1 to repress transcription of
      the TATA binding protein, TBP. Maf1 targets an Elk-1-binding site in the TBP
      promoter, and its occupancy of this region is reciprocal with that of Elk-1.
      Similarly, Maf1 occupancy of Pol III genes is inversely correlated with that of
      the initiation factor TFIIIB and Pol III. The phenotypic consequences of reducing
      Maf1 expression include changes in cell morphology and the accumulation of actin
      stress fibers, whereas Maf1 overexpression suppresses anchorage-independent
      growth. Together with the ability of Maf1 to reduce biosynthetic capacity, these
      findings support the idea that Maf1 regulates the transformation state of cells.

PMID- 17499044
TI  - An antisense RNA inhibits translation by competing with standby ribosomes.
AB  - Most antisense RNAs in bacteria inhibit translation by competing with ribosomes
      for translation initiation regions (TIRs) on nascent mRNA. We propose a mechanism
      by which an antisense RNA inhibits translation without binding directly to a TIR.
      The tisAB locus encodes an SOS-induced toxin, and IstR-1 is the antisense RNA
      that counteracts toxicity. We show that full-length tisAB mRNA (+1) is
      translationally inactive and endonucleolytic processing produces an active mRNA
      (+42). IstR-1 binding inhibits translation of this mRNA, and subsequent RNase III
      cleavage generates a truncated, inactive mRNA (+106). In vitro translation,
      toeprinting, and structure mapping suggest that active, but not inactive, tisAB
      mRNAs contain an upstream ribosome loading or "standby" site. Standby binding is
      required for initiation at the highly structured tisB TIR. This may involve
      ribosome sliding to a transiently open tisB TIR. IstR-1 competes with ribosomes
      by base pairing to the standby site located approximately 100 nucleotides
      upstream.

PMID- 17499045
TI  - The site of action of oxazolidinone antibiotics in living bacteria and in human
      mitochondria.
AB  - The oxazolidinones are one of the newest classes of antibiotics. They inhibit
      bacterial growth by interfering with protein synthesis. The mechanism of
      oxazolidinone action and the precise location of the drug binding site in the
      ribosome are unknown. We used a panel of photoreactive derivatives to identify
      the site of action of oxazolidinones in the ribosomes of bacterial and human
      cells. The in vivo crosslinking data were used to model the position of the
      oxazolidinone molecule within its binding site in the peptidyl transferase center
      (PTC). Oxazolidinones interact with the A site of the bacterial ribosome where
      they should interfere with the placement of the aminoacyl-tRNA. In human cells,
      oxazolidinones were crosslinked to rRNA in the PTC of mitochondrial, but not
      cytoplasmic, ribosomes. Interaction of oxazolidinones with the mitochondrial
      ribosomes provides a structural basis for the inhibition of mitochondrial protein
      synthesis, which is linked to clinical side effects associated with oxazolidinone
      therapy.

PMID- 17499046
TI  - The transport signal on Sec22 for packaging into COPII-coated vesicles is a
      conformational epitope.
AB  - The mechanism of cargo concentration into ER-derived vesicles involves
      interactions between the COPII vesicular coat complex and cargo transport signals
      -peptide sequences of 10-15 residues. The SNARE protein Sec22 contains a signal
      that binds the COPII subcomplex Sec23/24 and specifies its endoplasmic reticulum
      (ER) exit as an unassembled SNARE. The 200 kDa crystal structure of Sec22 bound
      to Sec23/24 reveals that the transport signal is a folded epitope rather than a
      conventional short peptide sequence. The NIE segment of the SNARE motif folds
      against the N-terminal longin domain, and this closed form of Sec22 binds at the
      Sec23/24 interface. Thus, COPII recognizes unassembled Sec22 via a folded
      epitope, whereas Sec22 assembly into SNARE complexes would mask the NIE segment.
      The concept of a conformational epitope as a transport signal suggests packaging
      mechanisms in which a coat is sensitive to the folded state of a cargo protein or
      the assembled state of a multiprotein complex.

PMID- 17499047
TI  - Topologies of a substrate protein bound to the chaperonin GroEL.
AB  - The chaperonin GroEL assists polypeptide folding through sequential steps of
      binding nonnative protein in the central cavity of an open ring, via hydrophobic
      surfaces of its apical domains, followed by encapsulation in a hydrophilic
      cavity. To examine the binding state, we have classified a large data set of
      GroEL binary complexes with nonnative malate dehydrogenase (MDH), imaged by cryo
      electron microscopy, to sort them into homogeneous subsets. The resulting
      electron density maps show MDH associated in several characteristic binding
      topologies either deep inside the cavity or at its inlet, contacting three to
      four consecutive GroEL apical domains. Consistent with visualization of bound
      polypeptide distributed over many parts of the central cavity, disulfide
      crosslinking could be carried out between a cysteine in a bound substrate protein
      and cysteines substituted anywhere inside GroEL. Finally, substrate binding
      induced adjustments in GroEL itself, observed mainly as clustering together of
      apical domains around sites of substrate binding.

PMID- 17499048
TI  - The structure of the C-terminal domain of the protein kinase AtSOS2 bound to the
      calcium sensor AtSOS3.
AB  - The plant SOS2 family of protein kinases and their interacting activators, the
      SOS3 family of calcium-binding proteins, function together in decoding calcium
      signals elicited by different environmental stimuli. SOS2 is activated by Ca-SOS3
      and subsequently phosphorylates the ion transporter SOS1 to bring about cellular
      ion homeostasis under salt stress. In addition to possessing the kinase activity,
      members of the SOS2 family of protein kinases can bind to protein phosphatase
      2Cs. The crystal structure of the binary complex of Ca-SOS3 with the C-terminal
      regulatory moiety of SOS2 resolves central questions regarding the dual function
      of SOS2 as a kinase and a phosphatase-binding protein. A comparison with the
      structure of unbound SOS3 reveals the basis of the molecular function of this
      family of kinases and their interacting calcium sensors. Furthermore, our study
      suggests that the structure of the phosphatase-interaction domain of SOS2 defines
      a scaffold module conserved from yeast to human.

PMID- 17499049
TI  - A targeted multienzyme mechanism for selective microtubule polyglutamylation.
AB  - Polyglutamylases are enzymes that form polyglutamate side chains of variable
      lengths on proteins. Polyglutamylation of tubulin is believed to regulate
      interactions of microtubules (MTs) with MT-associated proteins and molecular
      motors. Subpopulations of MTs are differentially polyglutamylated, yet only one
      modifying enzyme has been discovered in mammals. In an attempt to better
      understand the heterogeneous appearance of tubulin polyglutamylation, we searched
      for additional enzymes and report here the identification of six mammalian
      polyglutamylases. Each of them has a characteristic mode of catalysis and
      generates distinct patterns of modification on MTs, which can be further
      diversified by cooperation of multiple enzymes. Polyglutamylases are restricted
      to confined tissues and subtypes of MTs by differential expression and
      localization. In conclusion, we propose a multienzyme mechanism of
      polyglutamylation that can explain how the diversity of polyglutamylation on
      selected types of MTs is controlled at the molecular level.

PMID- 17499053
TI  - Family-centered care in the perioperative area: an international perspective.
AB  - Family-centered care developed after research showed that children were
      emotionally compromised if separated from their parents during traumatic
      episodes. Few places within the health care system are more foreign and
      frightening to a child than the surgical department. Perioperative nursing
      evolved as a way to care for patients admitted to the OR for surgery. Family
      centered care provides a model for the care of a child within the perioperative
      environment. This article examines the development of both family-centered care
      and perioperative nursing from a historical perspective and explains how family
      centered care can be applied to perioperative nursing.

PMID- 17499050
TI  - Insights into the influence of nucleotides on actin family proteins from seven
      structures of Arp2/3 complex.
AB  - ATP is required for nucleation of actin filament branches by Arp2/3 complex, but
      the influence of ATP binding and hydrolysis are poorly understood. We determined
      crystal structures of bovine Arp2/3 complex cocrystallized with various bound
      adenine nucleotides and cations. Nucleotide binding favors closure of the
      nucleotide-binding cleft of Arp3, but no large-scale conformational changes in
      the complex. Thus, ATP binding does not directly activate Arp2/3 complex but is
      part of a network of interactions that contribute to nucleation. We compared
      nucleotide-induced conformational changes of residues lining the cleft in Arp3
      and actin structures to construct a movie depicting the proposed ATPase cycle for
      the actin family. Chemical crosslinking stabilized subdomain 1 of Arp2, revealing
      new electron density for 69 residues in this subdomain. Steric clashes with Arp3
      appear to be responsible for intrinsic disorder of subdomains 1 and 2 of Arp2 in
      inactive Arp2/3 complex.

PMID- 17499054
TI  - Innovations in postoperative pain management: continuous infusion of local
      anesthetics.
AB  - Patients and health care providers alike struggle with alleviating postoperative
      pain. Patients with unrelieved pain are less likely to cough, breathe deeply, or
      move easily after surgery, which adversely affects their recovery. Innovations in
      technology, such as continuous infusion of local anesthetics, have revolutionized
      postoperative pain management. Technological improvements in needles, catheter
      insertion techniques, and effortless drug delivery systems are facilitating
      prolonged analgesia with few adverse effects, increasing patient satisfaction,
      and expediting postoperative recovery.

PMID- 17499055
TI  - A team approach to the prevention of unplanned postoperative hypothermia.
AB  - Postoperative hypothermia (ie, a core temperature lower than 96.8 degrees F [36
      degrees C]), is a problem frequently seen in surgical patients, especially those
      undergoing total joint replacement. Patients who experience hypothermia may have
      increased recovery times and postoperative complications. A team of clinical
      staff members and personnel from the performance improvement (PI) department of a
      hospital used a PI model to incorporate use of preoperative forced-air warming
      blankets that resulted in improved postoperative core temperatures.

PMID- 17499056
TI  - An evaluation of a numbered surgical sponge product.
AB  - Surgical sponge counting is an essential patient safety measure in the OR in
      which all members of the surgical team must participate. The RN acting as
      circulator is responsible for accurately documenting sponge counts during the
      surgical procedure. A sequentially numbered sponge product was evaluated in a
      survey of OR personnel to determine ease of use and whether the product affected
      the flow of the surgical procedure. Survey respondents reported that the numbered
      sponge product was easy to use and did not lengthen or affect the flow of the
      surgical procedure. Respondents also indicated that the product may contribute to
      patient safety.

PMID- 17499057
TI  - World-class OR turnaround times: secrets uncovered.
AB  - One of the aspects of OR service that is most important to surgeons is quick OR
      turnaround times. Perioperative staff members and one orthopedic surgeon at the
      Community Hospital, Munster, Ind, have developed an innovative approach to the OR
      turnaround process that considerably increases efficiency and reduces average
      turnaround times. By assigning specific tasks to each perioperative team member,
      scheduling surgical procedures in order based on type of procedure, and drawing
      on individual team members' traits, the orthopedic surgeon is able to perform
      more procedures than other orthopedic surgeons in that facility in the same
      amount of time, which increases revenue for the hospital.

PMID- 17499058
TI  - Patient illiteracy.

PMID- 17499060
TI  - The Protecting 5 Million Lives from Harm campaign.

PMID- 17499063
TI  - 25,000-fold pre-concentration in a single step with liquid-phase microextraction.
AB  - Hollow fiber protected liquid-phase microextraction (LPME) was developed for
      large sample volume extractions in a single step, with special emphasis on
      extraction of basic drugs from environmental waters. Five antidepressant drugs
      were extracted from 1100 or 100 mL water samples, through approximately 50 microL
      of dihexyl ether immobilized in the pores in the wall of a porous hollow fiber
      (liquid membrane), and into 20 microL of 10 mM HCl or HCOOH as the acceptor
      solution. Extractions were performed for 60 or 120 min supported by magnetic
      stirring at 800 rpm, and hereafter the acceptor solution was directly injected in
      HPLC-UV or HPLC-MS. Compared with earlier work on LPME from small sample volumes,
      both closing the hollow fiber and the type of liquid membrane was found to be
      critical for large volume extractions. The hollow fibers were carefully closed
      with a small piece of metal wire, dihexyl ether was used as the liquid membrane,
      and pH in the sample was adjusted to 11.8 with NaOH. Recoveries from 1100 mL
      samples were in the range 33-49%, and enrichments were in the range 18,000-27,000
      after 120 min of extraction. With HPLC-MS, the drugs were detected down to the 5
      30 pg L(-1) level. Within-day precision was within 12.4-20.6% R.S.D. (n=6),
      whereas between-day precision was within 17.6 and 37.2% R.S.D. Linearity was
      obtained in the range 1-500 ng L(-1) with r2-values between 0.982 and 0.994. The
      proposed LPME system was utilized to detect the five antidepressants in
      wastewater from the city of Tromso in Northern Norway.

PMID- 17499064
TI  - Microwave-assisted headspace single-drop microextration of chlorobenzenes from
      water samples.
AB  - A one-step and in-situ sample preparation method used for quantifying
      chlorobenzene compounds in water samples has been developed, coupling microwave
      and headspace single-drop microextraction (MW-HS-SDME). The chlorobenzenes in
      water samples were extracted directly onto an ionic liquid single-drop in
      headspace mode under the aid of microwave radiation. For optimization, a Plackett
      Burman screening design was initially used, followed by a mixed-level factorial
      design. The factors considered were: drop volume, aqueous sample volume, stirring
      speed, ionic strength, extraction time, ionic liquid type, microwave power and
      length of the Y-shaped glass-tube. The optimum experimental conditions found from
      this statistical evaluation were: a 5 microL microdrop of 1-hexyl-3
      methylimidazolium hexafluorophosphate exposed for 20 min to the headspace of a 30
      mL aqueous sample, irradiated by microwaves at 200 W and placed in a 50 mL
      spherical flask connected to a 25 cm Y-shaped glass-tube. Under the optimised
      experimental conditions, the response of a high performance liquid
      chromatographic system was found to be linear over the range studied and with
      correlation coefficients ranging between 0.9995 and 0.9999. The method showed a
      good level of repeatability, with relative standard deviations varying between
      2.3 and 8.3% (n=5). Detection limits were found in the low microg L(-1) range
      varying between 0.016 and 0.039 microg L(-1). Overall, the performance of the
      proposed method demonstrated the favourable effect of microwave sample
      irradiation upon HS-SDME. Finally, recovery studies from different types of
      environmental water samples revealed that matrix had little effect upon
      extraction.

PMID- 17499065
TI  - Extractive liquid-liquid spectrophotometric procedure for the determination of
      thiocyanate ions employing the ion pair reagent amiloride monohydrochloride.
AB  - An accurate, inexpensive and less laborious liquid-liquid extractive
      spectrophotometric procedure for the determination of thiocyanate ions in aqueous
      media has been developed. The method has been based upon the formation of a
      yellow colored complex ion associate of the ion-pairing reagent 1-(3, 5-diamino-6
      chloropyrazinecarboxyl) guanidine hydrochloride monohydrate, namely amiloride
      hydrochloride, DPG+.Cl- and the thiocyanate ions in aqueous media containing HNO3
      (0.5 mol L(-1)) and subsequent extraction with 4-methyl-2-pentanone. The
      absorption electronic spectrum of the ion associate showed one well-defined peak
      at lambda(max) 366 nm. The stoichiometric mole ratio of DPG+.Cl- to the
      thiocyanate ions is 1:1. The effective molar absorptivity (epsilon) of the ion
      associate at lambda(max) 366 nm is 1.1+/-0.1x10(4) L mol(-1) cm(-1). The
      extraction constants (K(d), K(ex), and beta) enabled a simple and convenient use
      of the developed binary ion associate for the extractive spectrophotometric
      determination of traces of thiocyanate ions in the aqueous media. Beer's law and
      Ringbom's plots are obeyed in the concentration range 0.05-10 and 0.1-7 microg
      mL(-1) of the thiocyanate ions, respectively with a relative standard deviation
      of +/-2.3%. The calculated lower limits of detection (LOD) and quantitation (LOQ)
      of the developed procedure for the thiocyanate ions were found equal to 0.02 and
      0.066 microg mL(-1), respectively. The developed method has been applied for the
      determination of trace amounts of thiocyanate ions in tap-, waste- and natural
      water samples and compared successfully with the reported methods at the 95%
      confidence level. The proposed method was also applied successfully for the
      determination of thiocyanate ions in saliva samples.

PMID- 17499066
TI  - Investigation on the interaction of tetrachloride fluorescein-bovine serum
      albumin-beta-cyclodextrin and the determination of protein by flow injection
      analysis.
AB  - In this paper, a simple and sensitive flow injection analysis (FIA) for the
      determination of protein with spectroscopic probe was developed. This method was
      based on the investigation of the interaction of tetrachloride fluorescein
      (2,4,5,7-tetrachloro-3,6-fluorandiol)-bovine serum albumin (BSA), the coupling
      reaction of protein with tetrachloride fluorescein (TCFS) which was used as a
      spectroscopic probe in the presence of beta-cyclodextrin (beta-CD). The
      interaction mechanism and the main factors affecting the determination were
      investigated in details. Under the optimum conditions, the linear range and
      detection limit were 0.0-28.0 microg mL(-1) and 0.76 microg mL(-1), respectively.
      The proposed method has been used to determine albumin in serum albumin with
      satisfactory results.

PMID- 17499067
TI  - Direct determination of glyphosate using hydrophilic interaction chromatography
      with coulometric detection at copper microelectrode.
AB  - A simple, rapid, and low-cost coulometric method for direct detection of
      glyphosate using hydrophilic interaction chromatography is presented. The
      principle of detection is based on the enhancement of the anodic current of
      copper microelectrode in the presence of complexing agents, such as glyphosate,
      with the formation of a soluble Cu(II) complex. Under optimized conditions, the
      limit of detection (S/R=3) for glyphosate was 0.1 mg L(-1) (0.59 microM) without
      any preconcentration method. The calibration curve has been found linear in all
      concentration range tested (from limit of detection to 34 mg L(-1)) with an
      excellent correlation coefficient (0.9999). The present method was successfully
      applied for the determination of glyphosate in fruit juices without any kind of
      extraction, clean-up, or preconcentration step, with recoveries of 92 and 90% for
      apple and grape juice, respectively.

PMID- 17499068
TI  - Fabrication and characterization of Meldola's blue/zinc oxide hybrid electrodes
      for efficient detection of the reduced form of nicotinamide adenine dinucleotide
      at low potential.
AB  - We report the synthesis and the electrochemical properties of hybrid films made
      of zinc oxide (ZnO) and Meldola's blue dye (MB) using cyclic voltammetry (CV).
      MB/ZnO hybrid films were electrochemically deposited onto glassy carbon, gold and
      indium tin oxide-coated glass (ITO) electrodes at room temperature (25+/-2
      degrees C) from the bath solution containing 0.1 M Zn(NO3)2, 0.1 M KNO3 and 1x10(
      4) MMB. The surface morphology and deposition kinetics of MB/ZnO hybrid films
      were studied by means of scanning electron microscopy (SEM), atomic force
      microscopy (AFM) and electrochemical quartz crystal microbalance (EQCM)
      techniques, respectively. SEM and AFM images of MB/ZnO hybrid films have revealed
      that the surfaces are well crystallized, porous and micro structured. MB
      molecules were immobilized and strongly fixed in a transparent inorganic matrix.
      MB/ZnO hybrid films modified glassy carbon electrode (MB/ZnO/GC) showed one
      reversible redox couple centered at formal potential (E0') -0.12 V (pH 6.9). The
      surface coverage (gamma) of the MB immobilized on ZnO/GC was about 9.86x10(-12)
      mol cm(-2) and the electron transfer rate constant (ks) was determined to be 38.9
      s(-1). The MB/ZnO/GC electrode acted as a sensor and displayed an excellent
      specific electrocatalytic response to the oxidation of nicotinamide adenine
      dinucleotide (NADH). The linear response range between 50 and 300 microM NADH
      concentration at pH 6.9 was observed with a detection limit of 10 microM (S/N=3).
      The electrode was stable during the time it was used for the full study (about 1
      month) without a notable decrease in current. Indeed, dopamine (DA), ascorbic
      acid (AA), acetaminophen (AP) and uric acid (UA) did not show any interference
      during the detection of NADH at this modified electrode.

PMID- 17499069
TI  - Use of chemically modified thermoresponsive copolymers for the detection of C
      reactive protein.
AB  - Fluorescence intensity of N-isopropylacrylamide-glycidyl methacrylate (NIPAAm
      GMA) copolymer conjugated with fluoreseinamine isomer1 was found to decrease
      considerably in the presence of NIPAAm-GMA copolymer containing O
      phosphorylethanolamine (PEA), the specific ligand of C-reactive protein (CRP).
      The decrease in the emission intensity was reasoned due to the quenching of the
      fluorescence through the interaction of the polymer chains. The emission
      intensity was, however, found to increase rapidly when CRP was added in to the
      solution containing the polymers. The intensity of fluorescence emission was
      increased by five-fold in the presence of CRP as low as 20 ng mL(-1). Albumin,
      the major blood protein, did not show any interference in the emission. The
      presence of a low molecular protein, cytochrome c, on the fluorescence spectra
      was also studied and this protein also found not have any influence in binding of
      CRP onto the ligand indicating that other proteins irrespective of their
      molecular weights did not influence the measurement. A definite correlation was
      found between the concentration of CRP and the fluorescence intensity. The method
      appears to be very sensitive and easy to perform. The study reflects, for the
      first time, the scope of using copolymeric combinations for the measurement of
      CRP without the use of antibody.

PMID- 17499070
TI  - Characterisation of antibodies to chloramphenicol, produced in different species
      by enzyme-linked immunosorbent assay and biosensor technologies.
AB  - Six polyclonal antisera to chloramphenicol (CAP) were successfully raised in
      camels, donkeys and goats. As a comparison of sensitivity, IC50 values ranged
      from 0.3 ng mL(-1) to 5.5 ng mL(-1) by enzyme-linked immunosorbent assay (ELISA)
      and from 0.7 ng mL(-1) to 1.7 ng mL(-1) by biosensor assay. The introduction of
      bovine milk extract improved the sensitivity of four of the antisera by ELISA and
      two by biosensor assay; a reduction in sensitivity of the remaining antisera
      ranged by a factor of 1.1-2.6. Porcine kidney extract reduced the sensitivity of
      all the antisera by a factor ranging from 1.1 to 7 by ELISA and a factor of 1.5
      to 4 by biosensor. A low cross-reactivity with thiamphenicol (TAP) and
      florfenicol (FF) was displayed by antiserum G2 (1.2% and 18%, respectively) when
      a homologous ELISA assay format was employed. No cross-reactivity was displayed
      by any of the antisera when a homologous biosensor assay format was employed.
      Switching to a heterologous ELISA format prompted three of the antisera to
      display more significant cross-reactivity with TAP and FF (53% and 82%,
      respectively, using D1). The heterologous biosensor assay also increased the
      cross-reactivity of D1 for TAP and FF (56% and 129%, respectively) and of one
      other antiserum (G1) to a lesser degree. However, unlike the ELISA, the
      heterologous biosensor assay produced a substantial reduction in sensitivity (by
      a factor of 6 for D1).

PMID- 17499072
TI  - Enzyme immunoassay for semicarbazide--the nitrofuran metabolite and food
      contaminant.
AB  - Semicarbazide (SEM), the marker residue for the banned nitrofuran veterinary
      antibiotic nitrofurazone (NFZ), has been detected regularly in foods (47% of
      recent nitrofuran EU Rapid Alerts involve SEM). However, the validity of SEM as a
      definitive marker for NFZ has been undermined by SEM arising from other sources
      including azodicarbonamide, a plastics blowing agent and flour treatment
      additive. An inexpensive screening test for SEM in food matrices is needed--all
      SEM testing currently uses expensive LC-MS/MS instrumentation. We now report the
      first production of antibodies against derivatised SEM. A novel carboxyphenyl SEM
      derivative was used to raise a polyclonal antibody that has been incorporated
      into a semi-quantitative microtitre plate ELISA, validated according to the
      criteria set out in Commission Decision 2002/657/EC, for use with chicken muscle.
      The antibody is highly specific for derivatised SEM, cross-reactivity being 1.7%
      with NFZ and negligible with a wide range of other nitrofurans and poultry drugs.
      Samples are derivatised with o-nitrobenzaldehyde and simultaneously protease
      digested before extraction by cation exchange SPE. The ELISA has a SEM detection
      capability (CCbeta) of 0.25 microg kg(-1) when a threshold of 0.21 microg kg(-1)
      is applied to the selection of samples for confirmation (lowest observed 0.25
      microg kg(-1) fortified sample, n=20), thus satisfying the EU nitrofurans'
      minimum required performance limit of 1 microg kg(-1). NFZ-incurred muscles (12)
      containing SEM at 0.5-5.0 microg kg(-1) by LC-MS/MS, all screened positive by
      this ELISA protocol which is also applicable to egg and chicken liver.

PMID- 17499073
TI  - Quantitative structure-retention relationship for the Kovats retention indices of
      a large set of terpenes: a combined data splitting-feature selection strategy.
AB  - A data set consisting of a large number of terpenoids, the widely distributed
      compounds in nature that are found in abundance in higher plants, have been used
      to develop a quantitative structure property relationship (QSPR) for their Kovats
      retention index. QSPR models are usually obtained by splitting the data into two
      sets including calibration (or training) and prediction (or validation). All
      model building steps, especially feature selection procedure, are performed using
      this initial splitting, and therefore the performances of the resulted models are
      highly dependent on the initial data splitting. To investigate the effects of
      data splitting on the feature selection in the current article we proposed a
      combined data splitting-feature selection (CDFS) methodology for QSPR model
      development by producing several different training/validation/test sets, and
      repeating all of the model building studies. In this method, data splitting is
      achieved many times and in each case feature selection is performed. The resulted
      models are compared for similarity and dissimilarity between the selected
      descriptors. The final model is one whose descriptors are the common variables
      between all of resulted models. The method was applied to QSPR study of a large
      data set containing the Kovats retention indices of 573 terpenoids. A final 8
      parametric multilinear model with constitutional and topological indices was
      obtained. Cross-validation indicated that the model could reproduce more than 90%
      of variances in the Kovats retention data. The relative error of prediction for
      an external test set of 50 compounds was 3.2%. Finally, to improve the results,
      structure-retention relationships were followed by nonlinear approach using
      artificial neural networks and consequently better results were obtained.

PMID- 17499074
TI  - Multivariate methods on the excitation emission matrix fluorescence spectroscopic
      data of diesel-kerosene mixtures: a comparative study.
AB  - Quantitative determination of kerosene fraction present in diesel has been
      carried out based on excitation emission matrix fluorescence (EEMF) along with
      parallel factor analysis (PARAFAC) and N-way partial least squares regression (N
      PLS). EEMF is a simple, sensitive and nondestructive method suitable for the
      analysis of multifluorophoric mixtures. Calibration models consisting of varying
      compositions of diesel and kerosene were constructed and their validation was
      carried out using leave-one-out cross validation method. The accuracy of the
      model was evaluated through the root mean square error of prediction (RMSEP) for
      the PARAFAC, N-PLS and unfold PLS methods. N-PLS was found to be a better method
      compared to PARAFAC and unfold PLS method because of its low RMSEP values.

PMID- 17499075
TI  - Comparative proteomic analysis of B. cenocepacia using two-dimensional liquid
      separations coupled with mass spectrometry.
AB  - Burkholderia cenocepacia is an important respiratory pathogen in persons with
      cystic fibrosis. We compared the proteomes of clinical and environmental isolates
      of B. cenocepacia by using a 2D liquid separation method coupled with mass
      spectrometry. Proteome maps of four B. cenocepacia isolates were generated. In
      the first dimension, 5 mg of protein from each isolate was fractionated by
      chromatofocusing (CF) in the range of pH 4.0-7.0. In the second dimension, each
      CF fraction was separated by NPS-RP-HPLC. Results of the 2D liquid separation
      were visualized as 2D UV maps, which allowed direct comparison of proteomes with
      high resolution and reproducibility. From the proteomic comparison of the four
      isolates, 38 of 96 differentially abundant proteins were identified by peptide
      mass fingerprinting and MS/MS sequence analysis using a partially annotated B.
      cenocepacia protein database. Many of the identified proteins in the clinical
      isolates are involved in gene translation and bacterial virulence such as
      transmissibility, resistance, and quorum sensing.

PMID- 17499076
TI  - Rapid uranium preconcentration and separation method from fresh water samples for
      total U and 235U/238U isotope ratio measurements by ICP-MS.
AB  - A simple and rapid method using TRU resin cartridges (Eichrom Technologies, Inc.,
      USA) and quadrupole ICP-MS for total uranium (U) and 235U/238U isotope ratio
      measurements in fresh water samples was investigated. After U extraction on the
      resin by sample solution loading, three alkaline reagents, tetramethyl ammonium
      hydroxide (TMAH), NaOH and NH4OH were studied for U elution behavior from the
      resin cartridges and applicability of these eluates was evaluated with respect to
      direct introduction to ICP-MS. Among the studied eluants, TMAH showed the best
      results with high U recovery and no counting interferences with internal standard
      elements such as thallium and bismuth. Moreover, U in water samples was separated
      from many major and minor elements with the TRU cartridges. Almost all U was
      concentrated in 10 mL of 0.014 M TMAH in 2 h using 200 mL of water sample.

PMID- 17499077
TI  - Diffusive gradients in thin films technique for uranium measurements in river
      water.
AB  - The diffusive gradients in thin films technique (DGT) was used for uranium
      measurements in water. DGT devices with Dowex resin binding phase (Dow DGT) were
      tested in synthetic river water, which gave 84% response to total uranium
      concentration. The devices were also deployed in natural river water and compared
      to devices with other types of binding phases, Chelex 100 resin beads imbedded in
      polyacrylamide hydrogel (Chelex DGT) and DE 81 anion exchange membrane (DE DGT),
      deployed in the same location at the same time. The measurement by Dow DGT was
      the lowest among the different types of the DGT devices, 45% of total uranium,
      while measurement by DE DGT was the highest, 98% of total uranium. The results
      achieved by the three types of DGT devices were explained by three DGT working
      mechanisms, equilibrium between complexes of resin/uranyl carbonates and
      complexes of resin/competitive ligands in water, effective reduction of uranyl
      carbonate concentration by the binding phase and dissociation of UO2(CO3)2(2-)
      and UO2(CO3)3(4-) within the diffusive layer in a DGT device. It is hoped that by
      deploying the DGT devices with different binding phases in natural waters,
      additional information on uranium speciation could be obtained.

PMID- 17499078
TI  - The Environmental Reward Observation Scale (EROS): development, validity, and
      reliability.
AB  - Researchers acknowledge a strong association between the frequency and duration
      of environmental reward and affective mood states, particularly in relation to
      the etiology, assessment, and treatment of depression. Given behavioral theories
      that outline environmental reward as a strong mediator of affect and the
      unavailability of an efficient, reliable, and valid self-report measure of
      environmental reward, we developed the Environmental Reward Observation Scale
      (EROS) and examined its psychometric properties. In Experiment 1, exploratory
      factor analysis supported a unidimensional 10-item measure with strong internal
      consistency and test-retest reliability. When administered to a replication
      sample, confirmatory factor analysis suggested an excellent fit to the 1-factor
      model and convergent/discriminant validity data supported the construct validity
      of the EROS. In Experiment 2, further support for the convergent validity of the
      EROS was obtained via moderate correlations with the Pleasant Events Schedule
      (PES; MacPhillamy & Lewinsohn, 1976). In Experiment 3, hierarchical regression
      supported the ecological validity of the EROS toward predicting daily diary
      reports of time spent in highly rewarding behaviors and activities. Above and
      beyond variance accounted for by depressive symptoms (BDI), the EROS was
      associated with significant incremental variance in accounting for time spent in
      both low and high reward behaviors. The EROS may represent a brief, reliable and
      valid measure of environmental reward that may improve the psychological
      assessment of negative mood states such as clinical depression.

PMID- 17499079
TI  - Social anxiety in Chinese- and European-heritage students: the effect of
      assessment format and judgments of impairment.
AB  - We examined whether social anxiety resulted in different levels of perceived
      impairment in first- and second-generation students of Chinese heritage (ns=65
      and 47) compared to their European-heritage counterparts (n=60). We also used a
      modified version of the Anxiety Disorders Interview Schedule (ADIS-IV) to
      determine whether the 3 groups responded differently to the social demands
      inherent in interview-based assessment compared to questionnaires. First
      generation Chinese participants reported significantly greater social anxiety and
      impairment than the European heritage group in response to both interviews and
      questionnaires. The results argue against the notion that social anxiety is
      perceived to cause less impairment in Chinese North Americans or that interview
      based assessment has a differential effect on the Chinese- and European-heritage
      groups.

PMID- 17499080
TI  - The frequency, nature, and effects of naturally occurring appearance-focused
      social comparisons.
AB  - This research examined the effects of naturally occurring appearance-focused
      social comparisons on women's affect, body satisfaction, and weight-related
      cognitions. During their daily activities, women reporting body dissatisfaction
      (n=53) and women reporting body satisfaction (n=34) recorded their reactions to
      comparison information. Body-dissatisfied women engaged in more comparisons and a
      greater proportion of upward comparisons than body-satisfied women. Upward
      comparisons were associated with an increase in negative affect, body
      dissatisfaction, and thoughts of exercising for both groups; however, body
      dissatisfied women experienced a greater increase in thoughts of dieting
      following upward comparisons. The daily effects of comparison information on body
      dissatisfied women were examined; upward comparisons were associated with
      increases in daily negative affect, body dissatisfaction, and weight-related
      cognitions.

PMID- 17499081
TI  - Depressive realism and attributional style: implications for individuals at risk
      for depression.
AB  - Prior research has found that depressed individuals are more realistic in their
      interpretations of certain events than nondepressed individuals. However, the
      implications of this finding for the etiology of depressive disorders have never
      been clarified. The current investigation sought to remedy this situation by
      exploring realism in the context of a well-validated, cognitive diathesis-stress
      theory of the etiology of a subtype of depression: hopelessness theory (Abramson,
      L. Y., Metalsky, G. I., & Alloy, L. B. (1989). Hopelessness depression: A theory
      based subtype of depression. Psychological Review, 96, 358-372). A sample of 239
      college students, including groups of participants with depressogenic versus
      nondepressogenic attributional styles, recorded the causes they assigned to
      events; the extent to which their attributions were objectively realistic was
      evaluated. A comparison of the degree of objectivity was also made between
      dysphoric and nondysphoric individuals. Contrary to expectations derived from the
      depressive realism hypothesis, dysphoric individuals exhibited less realistic
      attributions as compared to nondysphoric individuals. Further, individuals at
      risk for depression evidenced a pessimistic bias, while individuals not at risk
      evidenced an optimistic bias.

PMID- 17499082
TI  - Does altering the writing instructions influence outcome associated with written
      disclosure?
AB  - This study examined the effect of changing the instructional set for written
      disclosure on psychological and physical health reports among traumatized college
      students with current posttraumatic stress symptoms. Eighty-two participants were
      randomly assigned to one of three writing conditions that focused on emotional
      expression (EE), insight and cognitive assimilation, or to a control condition.
      Participants assigned to the EE condition reported significant improvements in
      psychological and physical health 1 month following the writing sessions relative
      to the other two conditions. The EE participants also reported and displayed
      significantly greater initial psychophysiological reactivity and subsequent
      habituation compared with the other two conditions. These findings suggest the
      importance of emphasizing emotional expression during written disclosure and
      underscore the importance of examining how modifying the written disclosure
      protocol can affect outcome.

PMID- 17499083
TI  - Can the components of a cognitive model predict the severity of generalized
      anxiety disorder?
AB  - Over the past decade, a number of well-controlled studies have supported the
      validity of a cognitive model of generalized anxiety disorder (GAD) that has four
      main components: intolerance of uncertainty, positive beliefs about worry,
      negative problem orientation, and cognitive avoidance. Although these studies
      have shown that the model components are associated with high levels of worry in
      nonclinical samples and with a diagnosis of GAD in clinical samples, they have
      not addressed the question of whether the model components can predict the
      severity of GAD. Accordingly, the present study sought to determine if the model
      components are related to diagnostic severity, worry severity, and somatic
      symptom severity in a sample of 84 patients with a primary diagnosis of GAD. All
      model components were related to GAD severity, although positive beliefs about
      worry and cognitive avoidance were only modestly associated with the severity of
      the disorder. Intolerance of uncertainty and negative problem orientation had
      more robust relationships with the severity of GAD (and with worry severity, in
      particular). When participants were divided into Mild, Moderate, and Severe GAD
      groups, intolerance of uncertainty and negative problem orientation distinguished
      the Moderate and Severe GAD groups from the Mild GAD group, even when age,
      gender, and depressive symptoms were statistically controlled. Overall, the
      results lend further support to the validity of the model and suggest that
      intolerance of uncertainty and negative problem orientation are related to the
      severity of GAD, independently of sociodemographic and associated clinical
      factors. The theoretical and clinical implications of the findings are discussed.

PMID- 17499085
TI  - The reverse of social anxiety is not always the opposite: the reverse-scored
      items of the social interaction anxiety scale do not belong.
AB  - Although well-used and empirically supported, the Social Interaction Anxiety
      Scale (SIAS) has a questionable factor structure and includes reverse-scored
      items with questionable utility. Here, using samples of undergraduates and a
      sample of clients with social anxiety disorder, we extend previous work that
      opened the question of whether the reverse-scored items belong on the scale.
      First, we successfully confirmed the factor structure obtained in previous
      samples. Second, we found the reverse-scored items to show consistently weaker
      relationships with a variety of comparison measures. Third, we demonstrated that
      removing the reverse-scored questions generally helps rather than hinders the
      psychometric performance of the SIAS total score. Fourth, we found that the
      reverse-scored items show a strong relationship with the normal personality
      characteristic of extraversion, suggesting that the reverse-scored items may
      primarily assess extraversion. Given the above results, we suggest investigators
      consider performing data analyses using only the straightforwardly worded items
      of the SIAS.

PMID- 17499084
TI  - A randomized controlled trial of self-directed versus therapist-directed
      cognitive-behavioral therapy for obsessive-compulsive disorder patients with
      prior medication trials.
AB  - Cognitive-behavioral therapy incorporating exposure and response prevention (ERP)
      is widely considered a first-line psychosocial treatment for patients with
      obsessive-compulsive disorder (OCD). However, a number of obstacles prevent many
      patients from receiving this treatment, and self-administered ERP may be a useful
      alternative or adjunct. Forty-one adult outpatients with a primary diagnosis of
      OCD, who reported at least 1 current or previous adequate medication trial, were
      randomly assigned to self-administered or therapist-administered ERP. Patients in
      both treatment conditions showed statistically and clinically significant symptom
      reduction. However, patients receiving therapist-administered ERP showed a
      superior response in terms of OCD symptoms and self-reported functional
      impairment. We discuss several potential reasons for the superiority of therapist
      administered treatment, and propose a stepped-care integration of self
      administered and therapist-administered interventions for OCD.

PMID- 17499087
TI  - Implant-retained digital prostheses with custom-designed attachments: a clinical
      report.
AB  - A patient with traumatic amputation of 4 digits was rehabilitated with implant
      supported digital prostheses. Implants were placed in the residual bone structure
      of the thumb, index, middle, and ring fingers. After osseointegration was
      complete, custom-designed retentive attachments and silicone digital prostheses
      were fabricated to restore the natural appearance of the hand, and some degree of
      tactile sensation was also achieved.

PMID- 17499086
TI  - Restoring a severely resorbed maxillary anterior partially edentulous space using
      a one-piece titanium implant fixed partial denture: a clinical report.
AB  - This article describes the treatment provided for a patient presenting with a
      severely resorbed partially edentulous maxillary anterior space and a previously
      placed implant. After the patient refused removal of the existing implant and
      additional grafting of hard and soft tissue, the nonsalvageable teeth were
      removed and 2 endosseous implants were placed. A 1-piece titanium implant fixed
      partial denture was used to restore the missing portions of the soft and hard
      tissues. This clinical report details the treatment of this challenging
      restorative dilemma.

PMID- 17499088
TI  - Hyperostosis in an orbital defect with craniofacial implants and open-field
      magnets: a clinical report.
AB  - An orbital facial prosthesis wearer was found to have significant hyperostosis in
      an exenterated orbit exposed to long-term, open field, rare earth magnets
      attached to craniofacial implants. Localized exophytic osseous formation was
      found in multiple areas around the exenterated orbit. The overall thickness of
      the walls of the exenterated orbit was approximately double that of the
      unaffected side. Magnetic field effect on bone formation and recommended
      treatment are discussed.

PMID- 17499089
TI  - Intraoral determination of the tolerance of dentists for perceptibility and
      acceptability of shade mismatch.
AB  - STATEMENT OF PROBLEM: There is little agreement in the dental literature as to
      how much color difference constitutes an acceptable shade mismatch or how much
      color difference is considered perceivable to observers. Most studies attempting
      to determine perceptibility and acceptability of tolerances for shade mismatches
      have been conducted under in vitro conditions that are not applicable to clinical
      scenarios. PURPOSE: The goal of this study was to determine valid acceptability
      and perceptibility tolerances for shade mismatch in an actual clinical scenario
      using spectroradiometric instrumentation. MATERIAL AND METHODS: A test denture
      was fabricated that allowed 10 maxillary left central incisors of varying shade
      mismatch with the right central incisor to be interchanged within the denture
      base. A spectroradiometer was used to determine the CIELAB coordinates and color
      differences (DeltaE) between the right central incisor and the interchangeable
      left central incisor denture teeth. The interchangeable denture teeth ranged
      uniformly from 1 DeltaE unit (visually undetectable) to greater than 10 DeltaE
      units (an obvious shade mismatch). The test denture with each of the
      interchangeable teeth was modeled by a subject to 28 dentists in a clinical
      setting. For each of the interchangeable teeth, dentist observers were asked if
      they could see a difference between the central incisors and, if so, whether the
      difference was acceptable. A Probit regression analysis was used to predict
      acceptability and perceptibility tolerances with 95% confidence limits. RESULTS:
      The predicted color difference at which 50% of the dentist observers could
      perceive a color difference (50/50 perceptibility) was 2.6 DeltaE units. The
      predicted color difference at which 50% of the subjects would remake the
      restoration due to color mismatch (clinically unacceptable color match) was 5.5
      DeltaE. Acceptability and perceptibility color tolerances at the 50/50 level were
      significantly different (P<.05), as their 95% confidence limits did not overlap.
      CONCLUSIONS: Tolerances for perceptibility were significantly lower than
      tolerances for acceptability for shade mismatch between 2 denture teeth.

PMID- 17499090
TI  - In vitro fracture strength and thermal shock resistance of metal-ceramic crowns
      with cast and machined AuTi frameworks.
AB  - STATEMENT OF PROBLEM: AuTi alloys with 1.6% to 1.7% (wt%) Ti provide sufficient
      bond strength to veneering ceramics, but the strength of entire metal-ceramic
      restorations fabricated from these alloys is not known. However, this information
      is important to assess the clinical performance of such materials. PURPOSE: This
      in vitro study evaluated the fracture strength and thermal shock resistance of
      metal-ceramic crowns with AuTi frameworks produced by milling or casting.
      MATERIAL AND METHODS: Frameworks of the alloy Au-1.7Ti-0.1Ir (wt%) (Esteticor
      Vision) were produced by milling or casting (test groups). A high-gold alloy
      (Esteticor Special) was used as the control. The frameworks were veneered with
      ceramic (VMK 95). Specimens (n=7) were loaded until fracture. Loads at failure
      (N) were recorded and the mean values statistically evaluated using 1-way
      analysis of variance and a post hoc Dunnett test (alpha=.05). To assess the
      crazing resistance of the veneering ceramic, 6 additional crowns of each group
      were subjected to a thermal shock test. Fractured surfaces were documented by
      scanning electron microscopy. Coefficients of thermal expansion of the materials
      used were measured (n=2) to assess the thermal compatibility between alloys and
      ceramic. RESULTS: The mean fracture strength of the crowns with machined AuTi
      frameworks (1294 +/- 236 N) was significantly lower (P=.012) than that of the
      cast AuTi frameworks (1680 +/- 150 N), but statistically not different than the
      high-gold alloy (1449 +/- 159 N). Bonding failure to the AuTi alloy predominantly
      occurred at the alloy-oxide interface. For the high-gold alloy, more ceramic
      residues were observed. In the thermal shock test, crowns with milled AuTi
      frameworks showed significantly higher thermal shock resistance compared to the
      other groups. The coefficients of thermal expansion (Esteticor Vision cast: 14.5
      microm/m.K; Esteticor Vision milled: 14.3 microm/m.K; Esteticor Special cast:
      13.7 microm/m.K) did not correlate with the results of the thermal shock test.
      CONCLUSION: The in vitro fracture strength of crowns with milled AuTi frameworks
      is lower than that obtained with cast AuTi frameworks, but comparable to those
      crowns produced with a high-gold alloy.

PMID- 17499091
TI  - Bond strengths of one- and two-step self-etch adhesive systems.
AB  - STATEMENT OF PROBLEM: One-bottle self-etching adhesives have been introduced that
      combine the etchant, primer, and adhesive into a single bottle in an effort to
      reduce the number of bonding steps. Limited research has been conducted comparing
      the efficacy of 1-bottle and 2-bottle self-etching adhesives. PURPOSE: This
      investigation evaluated the microtensile bond strength (MTBS) of 3 one-step self
      etching adhesives, 2 two-step self-etching adhesives, and a total-etch adhesive.
      A secondary objective was to evaluate the effect of an intermediary layer of
      elastic resin on the MTBS of 2 of the self-etching adhesives. MATERIAL AND
      METHODS: The MTBS of 3 one-step self-etching adhesives (G-Bond, iBond, and
      Clearfil S(3)), 2 two-step self-etching adhesives (Clearfil SE and Optibond Solo
      Plus Self-Etch), and a total-etch adhesive (Prime & Bond NT) was evaluated.
      Microtensile bond strength (MPa) was determined using composite resin (Herculite
      XRV) cylinders bonded to the dentin surface of human third molars (n=24) using 6
      bonding agents. Each bonded tooth specimen was longitudinally sectioned to
      produce bar-shaped specimens with a square cross-sectional nominal bond area of
      1.4 mm(2) (n=20). Bonded specimens were stored in distilled water at 37 degrees C
      +/- 2 degrees C for 72 hours, during which time they were subjected to thermal
      cycling (1500 cycles, in water baths of 5 degrees C and 55 degrees C, for a dwell
      time of 30 seconds). Testing was performed on a universal testing machine at a
      crosshead speed of 1.0 mm/min. One-way ANOVA, Ryan-Einot-Gabriel-Welsh multiple
      range test, and Wald chi square test, each using an overall alpha=.05, were
      performed on all data. Low-power (x20) microscopic examination of the bond
      failure was observed for each specimen. RESULTS: The 1-way ANOVA (P<.001) and
      Ryan-Einot-Gabriel-Welsh multiple range test (P<.05) showed significant
      differences between the mean MTBS values for several of the bonding agents
      tested. The Wald chi square test of the Weibull distribution showed significant
      differences between adhesives (P<.001). CONCLUSION: Of the bonding agents tested,
      significantly higher MTBS was obtained with the total-etch 2-stage adhesive. The
      results of this study suggest that there are similar bond strengths between the 1
      and 2-bottle self-etch adhesives.

PMID- 17499092
TI  - Microtensile bond strength between crown and root dentin and two adhesive
      systems.
AB  - STATEMENT OF PROBLEM: Since bonding agent effectiveness is usually evaluated on
      coronal substrates, available knowledge for judging the effectiveness of bonds to
      root dentin is insufficient. PURPOSE: The objective of this study was to evaluate
      the bond strength of 2 adhesive systems to crown, cervical finish line, and post
      space dentin. MATERIAL AND METHODS: Twenty bovine maxillary incisors were used in
      this study. Teeth were sectioned along the cemento-enamel junction using a low
      speed diamond blade to separate the crowns and roots. Then the crowns and roots
      were each divided into 2 groups, according to the 2 adhesive systems tested
      (n=10). The facial enamel surfaces of the crowns were abraded with 600-grit
      silicon carbide paper to expose flat, midcoronal dentin surfaces. Drills and a
      diamond rotary cutting instrument were used in a low-speed handpiece to prepare
      post spaces in the root canals. The same diamond rotary instrument was used to
      prepare horizontally flat surfaces in the cervical areas, similar to the
      horizontal aspect of a shoulder finish line. Composite resin was placed
      incrementally into the post spaces, over the flat cervical shoulder areas, and on
      the coronal dentin. Bonded beam specimens (0.5 mm(2) of cross-sectional area)
      derived from crown, cervical finish line, and post space dentin, were prepared
      for microtensile bond testing and tested in tension. Data were analyzed using 2
      way ANOVA and Tukey post hoc test (alpha=.05). Failure patterns of tested
      specimens were analyzed using scanning electron microscopy. RESULTS: The mean
      tensile bond strength values (SD) (MPa) were: Single Bond-crown: 29.8 (4.0);
      Single Bond-finish line: 18.7 (4.3); Single Bond-post space: 17.0 (4.8); Clearfil
      SE Bond-crown: 30.1 (6.4); Clearfil SE Bond-finish line: 30.4 (5.3); and Clearfil
      SE Bond-post space: 17.0 (4.2). Bond strengths to post space dentin were lower
      than those to coronal dentin for both adhesives (P<.001). However, no significant
      difference was observed between coronal and finish line dentin for Clearfil SE
      Bond. CONCLUSION: Bond strength was reduced when adhesives were used in bonding
      to post space dentin. Cervical finish line sites bonded using Clearfil SE Bond
      adhesive yielded bond strength similar to that of coronal dentin sites.

PMID- 17499093
TI  - Photoelastic stress analysis of various retention mechanisms on 3-implant
      retained mandibular overdentures.
AB  - STATEMENT OF PROBLEM: There are various stress transfer studies of 2- or 4
      implant-retained mandibular overdenture designs. However, the influence of
      various types of attachments and implant inclination on stress distribution of 3
      implant-retained mandibular overdenture designs has not been sufficiently
      assessed. PURPOSE: The purpose of this study was to compare the load transfer
      characteristics of 4 attachment systems for 3-implant-retained mandibular
      overdenture designs for vertically oriented and inclined implants. MATERIAL AND
      METHODS: Two photoelastic mandibular models were fabricated having 3 screw-type
      implants (3.7 x 14 mm with 4.8-mm diameter abutment platform) embedded in the
      interforaminal region. In the first model, the implants were parallel to each
      other and vertically oriented. In the second model, 1 implant in the midline was
      vertically oriented, and the other 2 implants were positioned 20 degrees
      divergent from the center implant. Four retention mechanisms were studied for
      each model--the Locator, Swissplus ball, Bredent bar, and Bredent bar-ball. The
      bar design connected the 3 implants, and the bar-ball design used the bar in a
      similar fashion but additionally incorporated distally placed ball attachments. A
      vertical force of 135 N was applied unilaterally to the central fossa of the
      right first molar. The resultant stresses that developed in the supporting
      structure were monitored photoelastically and recorded photographically. RESULTS:
      For the splinted and unsplinted 3-implant-retained overdenture designs evaluated,
      moderate and low level stresses were observed with different attachment systems.
      For both the vertically oriented and inclined implants, the bar-ball attachment
      system produced the lowest stress level. CONCLUSIONS: For vertical and inclined
      implant designs, lowest stress was transferred to all implants with the bar-ball
      attachment system, while moderate stresses were observed in implants on the
      loaded side with unsplinted attachment systems. The highest stress level observed
      with all attachment systems was moderate. For the vertical implant design, the
      observed stresses were distributed to all implants except with the ball
      attachment system, which demonstrated little discernible stresses on the non
      loaded side implant.

PMID- 17499094
TI  - Rapid prototyping technique for creating a radiation shield.
AB  - Radiation therapy for the treatment of head and neck skin cancer poses challenges
      because of the inherently uneven tissue topography of the face and the need to
      protect surrounding unaffected tissues. The use of a customized radiation shield
      that combines tissue-equivalent bolus material with protective material addresses
      these issues. This article describes a technique using rapid prototyping to
      design and fabricate an extraoral radiation shield. This innovative application
      provides an expedient, standardized approach for delivering radiotherapy to the
      face, which is not only more comfortable for the patient, but allows more precise
      treatment delivery.

PMID- 17499095
TI  - Alternate functional impression technique for implant-retained overdentures.

PMID- 17499096
TI  - A proximal contact adjustment and interproximal relief method.

PMID- 17499097
TI  - A digital video photographic technique for esthetic evaluation of anterior
      mandibular teeth.

PMID- 17499100
TI  - Leishmania and the leishmaniases: a parasite genetic update and advances in
      taxonomy, epidemiology and pathogenicity in humans.
AB  - Leishmaniases remain a major public health problem today despite the vast amount
      of research conducted on Leishmania pathogens. The biological model is
      genetically and ecologically complex. This paper explores the advances in
      Leishmania genetics and reviews population structure, taxonomy, epidemiology and
      pathogenicity. Current knowledge of Leishmania genetics is placed in the context
      of natural populations. Various studies have described a clonal structure for
      Leishmania but recombination, pseudo-recombination and other genetic processes
      have also been reported. The impact of these different models on epidemiology and
      the medical aspects of leishmaniases is considered from an evolutionary point of
      view. The role of these parasites in the expression of pathogenicity in humans is
      also explored. It is important to ascertain whether genetic variability of the
      parasites is related to the different clinical expressions of leishmaniasis. The
      review aims to put current knowledge of Leishmania and the leishmaniases in
      perspective and to underline priority questions which 'leishmaniacs' must answer
      in various domains: epidemiology, population genetics, taxonomy and
      pathogenicity. It concludes by presenting a number of feasible ways of responding
      to these questions.

PMID- 17499101
TI  - Human waterborne trematode and protozoan infections.
AB  - Waterborne trematode and protozoan infections inflict considerable morbidity on
      healthy, i.e., immunocompetent people, and may cause life-threatening diseases
      among immunocompromised and immunosuppressed populations. These infections are
      common, easily transmissible, and maintain a worldwide distribution, although
      waterborne trematode infections remain predominantly confined to the developing
      countries. Waterborne transmission of trematodes is enhanced by cultural
      practices of eating raw or inadequately cooked food, socio-economical factors,
      and wide zoonotic and sylvatic reservoirs of these helminths. Waterborne
      protozoan infections remain common in both developed and developing countries
      (although better statistics exist for developed countries), and their
      transmission is facilitated via contacts with recreational and surface waters, or
      via consumption of contaminated drinking water. The transmissive stages of human
      protozoan parasites are small, shed in large numbers in feces of infected people
      or animals, resistant to environmental stressors while in the environment, and
      few are (e.g., Cryptosporidium oocysts) able to resist standard disinfection
      applied to drinking water.

PMID- 17499102
TI  - The biology of gyrodactylid monogeneans: the "Russian-doll killers".
AB  - This article reviews the history of gyrodactylid research focussing on the unique
      anatomy, behaviour, ecology and evolution of the viviparous forms while
      identifying gaps in our knowledge and directions for future research. We provide
      the first summary of research on the oviparous gyrodactylids from South American
      catfish, and highlight the plesiomorphic characters shared by gyrodactylids and
      other primitive monogeneans. Of these, the most important are the crawling,
      unciliated larva and the spike sensilla of the cephalic lobes. These characters
      allow gyrodactylids to transfer between hosts at any stage of the life cycle,
      without a specific transmission stage. We emphasise the importance of progenesis
      in shaping the evolution of the viviparous genera and discuss the relative extent
      of progenesis in the different genera. The validity of the familial
      classification is discussed and we conclude that the most significant division
      within the family is between the oviparous and the viviparous genera. The older
      divisions into Isancistrinae and Polyclithrinae should be allowed to lapse. We
      discuss approaches to the taxonomy of gyrodactylids, and we emphasise the
      importance of adequate morphological and molecular data in new descriptions. Host
      specificity patterns in gyrodactylids are discussed extensively and we note the
      importance of host shifts, revealed by molecular data, in the evolution of
      gyrodactylids. To date, the most closely related gyrodactylids have not been
      found on closely related hosts, demonstrating the importance of host shifts in
      their evolution. The most closely related species pair is that of G. salaris and
      G. thymalli, and we provide an account of the patterns of evolution taking place
      in different mitochondrial clades of this species complex. The host specificity
      of these clades is reviewed, demonstrating that, although each clade has its
      preferred host, there is a range of specificity to different salmonids, providing
      opportunities for complex patterns of survival and interbreeding in Scandinavia.
      At the same time, we identify trends in systematics and phylogeny relevant to the
      G. salaris epidemics on Atlantic salmon in Norway, which can be applied more
      generally to parasite epidemiology and evolution. Although much of gyrodactylid
      research in the last 30 years has been directed towards salmonid parasites, there
      is great potential in using other experimental systems, such as the gyrodactylids
      of poeciliids and sticklebacks. We also highlight the role of glacial lakes and
      modified river systems during the ice ages in gyrodactylid speciation, and
      suggest that salmon infecting clades of G. salaris first arose from G. thymalli
      in such lakes, but failed to spread fully across Scandinavia before further
      dispersal was ended by rising sea levels. This dispersal has been continued by
      human activity, leading to the appearance of G. salaris as a pathogen in Norway.
      We review the history and current status of the epidemic, and current strategies
      for elimination of the parasite from Norway. Finally, we consider opportunities
      for further spread of the parasite within and beyond Europe.

PMID- 17499103
TI  - Human genetic diversity and the epidemiology of parasitic and other transmissible
      diseases.
AB  - This paper aims to review human genetic studies that are generally poorly known
      by parasitologists and scientists working on other pathogenic agents. The key
      proposals of this paper are as follows: (i) human susceptibility to transmissible
      diseases may often have a complex, multigenic background; (ii) recent discoveries
      indicate that major genomic rearrangements may be involved, possibly more so than
      DNA sequence; (iii) it is crucial to have a general population genetics framework
      of the human species based on neutral/historical markers to analyse reliably
      genetic susceptibility to infectious diseases; and (iv) the population level is a
      key factor. Ethnic diversity, a highly adaptive genetically driven phenotypic
      diversity, is possibly a valuable source for exploring human genetic
      susceptibility to transmissible diseases, since different populations have been
      exposed to drastically different geographic/climatic environments and different
      pathogens and vectors for tens of thousands of years. Studies dealing with human
      genetic susceptibility to transmissible diseases have mostly been based on the
      hypothesis that this factor is driven by only one or a few genes, and considered
      the individual more than the population level. Two different approaches have been
      developed for identifying the genes involved: (i) candidate genes and (ii) blind
      association studies (linkage analysis), screening the genome with a large number
      of high-resolution markers. Some loci involved in susceptibility to
      leishmaniosis, malaria and schistosomosis, for example, have already been
      identified. South American trypanosomosis (Chagas disease) is reviewed in detail
      to show the methodological problems of this classical approach. Current knowledge
      on the general impact of transmissible diseases on human genetic diversity,
      mainly HLA polymorphism, and the hopes raised by recent major international
      programmes such as the Human Genome Project (HGP), Human Genome Diversity Project
      (HGDP), International Human Haplotype Map Project (Hap Map) and extended
      databases, networks and networks of networks will also be reviewed.

PMID- 17499105
TI  - Basal ganglia macrocircuits.
AB  - This is the introductory chapter to an edited volume comprising 18 chapters
      written by 38 specially selected authors covering the anatomy, physiology,
      biochemistry/pharmacology and behavioral aspects of GABA in the basal ganglia. In
      this chapter the various nuclei of the basal ganglia are defined and their
      cellular structure, connections and function reviewed in brief in order to
      provide an orientation for the subsequent 17 chapters.

PMID- 17499106
TI  - GABA: homeostatic and pharmacological aspects.
AB  - The central nervous system (CNS) operates by a fine-tuned balance between
      excitatory and inhibitory signalling. In this context, the inhibitory
      neurotransmission may be of particular interest as it has been suggested that
      such neuronal pathways may constitute 'command pathways' and the principle of
      'dis-inhibition' leading ultimately to excitation may play a fundamental role
      (Roberts, E. (1974). Adv. Neurol., 5: 127-143). The neurotransmitter responsible
      for this signalling is gamma-aminobutyrate (GABA) which was first discovered in
      the CNS as a curious amino acid (Roberts, E., Frankel, S. (1950). J. Biol. Chem.,
      187: 55-63) and later proposed as an inhibitory neurotransmitter (Curtis, D.R.,
      Watkins, J.C. (1960). J. Neurochem., 6: 117-141; Krnjevic, K., Schwartz, S.
      (1967). Exp. Brain Res., 3: 320-336). The present review will describe aspects of
      GABAergic neurotransmission related to homeostatic mechanisms such as
      biosynthesis, metabolism, release and inactivation. Additionally, pharmacological
      and therapeutic aspects of this will be discussed.

PMID- 17499108
TI  - GABA(B) receptors: structure and function.
AB  - In the basal ganglia the effects of gamma-aminobutyrate (GABA) are mediated by
      both ionotropic (GABA(A)) and metabotropic (GABA(B)) receptors. Although the
      existence and widespread distribution in the CNS of the GABA(B) receptor had been
      established in the 1980s the field of GABA(B) research was revolutionized with
      the discovery that two related G-protein-coupled receptors (GPCRs) needed to
      dimerize to form the functional GABA(B) receptor at the cell surface. This
      finding lead to a number of studies of oligomerization in GPCRs and detailed
      pharmacological studies of the cloned receptors and their splice variants.
      Particular interest has focused on the proteins interacting with the receptor
      which may be important in mediating the longer term signalling effects of the
      receptor and modifying its cellular localization or physiology. The cloning of
      the GABA(B) receptors also lead to the identification of the first compounds
      interacting in an allosteric fashion with the receptor some of which may have
      therapeutic value. Most recently "knockouts" of both the GABA(B) subunits have
      been produced where in general as expected there is a loss of the majority of the
      inhibitory effects of the GABA(B) receptor.

PMID- 17499107
TI  - GABA(A) receptors: structure and function in the basal ganglia.
AB  - gamma-Aminobutyric acid type A (GABA(A)) receptors, the major inhibitory
      neurotransmitter receptors responsible for fast inhibition in the basal ganglia,
      belong to the superfamily of "cys-cys loop" ligand-gated ion channels. GABA(A)
      receptors form as pentameric assemblies of subunits, with a central Cl(-)
      permeable pore. On binding of two GABA molecules to the extracellular receptor
      domain, a conformational change is induced in the oligomer and Cl(-), in most
      adult neurons, moves into the cell leading to an inhibitory hyperpolarization.
      Nineteen mammalian subunit genes have been identified, each showing distinct
      regional and cell-type-specific expression. The combinatorial assembly of the
      subunits generates considerable functional diversity. Here we place the focus on
      GABA(A) receptor expression in the basal ganglia: striatum, globus pallidus,
      substantia nigra and subthalamic nucleus, where, in addition to the standard
      alpha1beta2/3gamma2 receptor subtype, significant levels of other subunits
      (alpha2, alpha3, alpha4, gamma1, gamma3 and delta) are expressed in some nuclei.

PMID- 17499109
TI  - The cellular, molecular and ionic basis of GABA(A) receptor signalling.
AB  - GABA(A) receptors mediate fast synaptic inhibition in the CNS. Whilst this is
      undoubtedly true, it is a gross oversimplification of their actions. The
      receptors themselves are diverse, being formed from a variety of subunits, each
      with a different temporal and spatial pattern of expression. This diversity is
      reflected in differences in subcellular targetting and in the subtleties of their
      response to GABA. While activation of the receptors leads to an inevitable
      increase in membrane conductance, the voltage response is dictated by the
      distribution of the permeant Cl(-) and HCO(3)(-) ions, which is established by
      anion transporters. Similar to GABA(A) receptors, the expression of these
      transporters is not only developmentally regulated but shows cell-specific and
      subcellular variation. Untangling all these complexities allows us to appreciate
      the variety of GABA-mediated signalling, a diverse set of phenomena encompassing
      both synaptic and non-synaptic functions that can be overtly excitatory as well
      as inhibitory.

PMID- 17499110
TI  - GABAergic inhibition in the neostriatum.
AB  - In the neostriatum, GABAergic inhibition arises from the action of at least two
      classes of inhibitory interneurons, and from recurrent collaterals of the
      principal cells. Interneurons receive excitatory input only from extrinsic
      sources, and so act in a purely feedforward capacity. Feedback inhibition arises
      from the recurrent collaterals of the principal cells. These two kinds of
      inhibition have functionally distinct effects on the principal cells. Inputs from
      interneurons are not very convergent. There are few inhibitory neurons, and so
      each principal cell receives inhibitory synaptic input from very few
      interneurons. But, they are individually powerful, and a single interneuron can
      substantially delay action potentials in a group of nearby principal cells.
      Recurrent inhibition is highly convergent, with each principal cell receiving
      inhibitory input from several hundred other such cells. Feedback inhibitory
      synaptic inputs individually have very weak effects, as seen from the soma. The
      differences in synaptic strength are not caused by differences in the release of
      transmitter or in sensitivity of the postsynaptic membrane. Rather, they arise
      from differences in the number of synaptic contacts formed on individual
      principal cells by feedforward or feedback axons, and from differences in
      synaptic location. Interneurons form their powerful synapses near the somata of
      principal cells, while most feedback synapses are more distal, where they
      interact with the two-state nonlinear properties of the principal cells'
      dendrite. This arrangement suggests that feedforward inhibition may serve in the
      traditional role for inhibition, adjusting the excitability of the principle
      neuron near the site of action potential generation. Feedback inhibitory synapses
      may interact with voltage-sensitive conductances in the dendrite to alter the
      electrotonic structure of the spiny cell.

PMID- 17499111
TI  - Globus pallidus external segment.
AB  - The external segment of the pallidum (GP(e)) is a relatively large nucleus
      located caudomedial to the neostriatum (Str). The GP(e) receives major inputs
      from two major basal ganglia input nuclei, the Str and the subthalamic nucleus
      (STN), and sends its output to many basal ganglia nuclei including the STN, the
      Str, the internal pallidal segment (GP(i)), and the substantia nigra (SN). Thus,
      the GPe can be placed at the center of the basal ganglia connection diagram (Fig.
      1(A)). From the viewpoint that emphasizes the direct and indirect pathways of the
      basal ganglia, the GP(e) is a component of the indirect pathway that relays Str
      inputs to the STN. The indirect pathway can be traced in Fig. 1(A), although it
      comprises only a part of multiple indirect pathways. This chapter begins with a
      brief description of the anatomical organization of the GP(e) followed by
      physiological and pharmacological characterizations of GABAergic responses in the
      GP(e).

PMID- 17499112
TI  - Globus pallidus internal segment.
AB  - The internal segment of the globus pallidus (GP(i)) gathers many bits of
      information including movement-related activity from the striatum, external
      segment of the globus pallidus (GP(e)), and subthalamic nucleus (STN), and
      integrates them. The GP(i) receives rich GABAergic inputs from the striatum and
      GP(e), and gamma-aminobutyric acid (GABA) receptors are distributed in the GP(i)
      in a specific manner. Thus, inputs from the striatum and GP(e) may control GP(i)
      activity in a different way. The GP(i) finally conveys processed information
      outside the basal ganglia. Changes in GABAergic neurotransmission have been
      reported in movement disorders and suggested to play an important role in the
      pathophysiology of the symptoms.

PMID- 17499113
TI  - The pars reticulata of the substantia nigra: a window to basal ganglia output.
AB  - Together with the internal segment of the globus pallidus (GP(i)), the pars
      reticulata of the substantia nigra (SNr) provides a main output nucleus of the
      basal ganglia (BG) where the final stage of information processing within this
      system takes place. In the last decade, progress on the anatomical organization
      and functional properties of BG output neurons have shed some light on the
      mechanisms of integration taking place in these nuclei and leading to normal and
      pathological BG outflow. In this review focused on the SNr, after describing how
      the anatomical arrangement of nigral cells and their afferents determines
      specific input-output registers, we examine how the basic electrophysiological
      properties of the cells and their interaction with synaptic inputs contribute to
      the spatio-temporal shaping of BG output. The reported data show that the
      intrinsic membrane properties of the neurons subserves a tonic discharge allowing
      BG to gate the transmission of information to motor and cognitive systems thereby
      contributing to appropriate selection of behavior.

PMID- 17499114
TI  - GABAergic control of the subthalamic nucleus.
AB  - The glutamatergic subthalamic nucleus (STN) is a key component of the basal
      ganglia, a group of subcortical brain nuclei important for voluntary movement and
      the site of dysfunction in Parkinson's disease. The rate and pattern of STN
      activity is precisely regulated by the reciprocally connected GABAergic external
      globus pallidus (GP(e)) and glutamatergic afferents from the cortex. Subthalamic
      neurons possess intrinsic membrane properties that underlie the autonomous
      generation of action potentials and complex forms of synaptic integration. Thus,
      GABA acting at GABA(A) and/or GABA(B) receptors can inhibit/reset autonomous
      activity by deactivating postsynaptic voltage-dependent Na(+) (Na(v)) channels
      and generate sufficient hyperpolarization for rebound burst firing, through the
      de-inactivation of postsynaptic voltage-dependent Ca(2+) (Ca(v)) and Na(v)
      channels. Feedback inhibition from the GP(e) can therefore paradoxically and
      transiently increase the efficacy of subsequent excitatory synaptic inputs, and
      thus enhance the response of the STN to rhythmic input from the cortex. Evidence
      is also provided that dopamine acting at post- and presynaptic receptors in the
      STN may, through actions on the integrative properties of STN neurons and
      activity-dependent synaptic plasticity, be critical for the patterning of STN
      neuronal activity in vivo. Taken together, these discoveries may be relevant for
      the emergence of correlated, rhythmic, burst firing in the dopamine-depleted STN
      of patients with PD.

PMID- 17499115
TI  - GABAergic control of substantia nigra dopaminergic neurons.
AB  - At least 70% of the afferents to substantia nigra dopaminergic neurons are
      GABAergic. The vast majority of these arise from the neostriatum, the external
      globus pallidus and the substantia nigra pars reticulata. Nigral dopaminergic
      neurons express both GABA(A) and GABA(B) receptors, and are inhibited by local
      application of GABA(A) or GABA(B) agonists in vivo and in vitro. However, in
      vivo, synaptic responses elicited by stimulation of neostriatal or pallidal
      afferents, or antidromic activation of nigral pars reticulata GABAergic
      projection neurons are mediated predominantly or exclusively by GABA(A)
      receptors. The clearest and most consistent role for the nigral GABA(B) receptor
      in vivo is as an inhibitory autoreceptor that presynaptically modulates GABA(A)
      synaptic responses that originate from all three principal GABAergic inputs. The
      firing pattern of dopaminergic neurons is also effectively modulated by GABAergic
      inputs in vivo. Local blockade of nigral GABA(A) receptors causes dopaminergic
      neurons to shift to a burst firing pattern regardless of the original firing
      pattern. This is accompanied by a modest increase in spontaneous firing rate. The
      GABAergic inputs from the axon collaterals of the pars reticulata projection
      neurons seem to be a particularly important source of a GABA(A) tone to the
      dopaminergic neurons, inhibition of which leads to burst firing. The globus
      pallidus exerts powerful control over the pars reticulata input, and through the
      latter, disynaptically over the dopaminergic neurons. Inhibition of pallidal
      output leads to a slight decrease in firing of the dopaminergic neurons due to
      disinhibition of the pars reticulata neurons whereas increased firing of pallidal
      neurons leads to burst firing in dopaminergic neurons that is associated with a
      modest increase in spontaneous firing rate and a significant increase in
      extracellular levels of dopamine in the neostriatum. The pallidal disynaptic
      disinhibitory control of the dopaminergic neurons dominates the monosynaptic
      inhibitory influence because of a differential sensitivity to GABA of the two
      nigral neuron types. Nigral GABAergic neurons are more sensitive to GABA(A)
      mediated inhibition than dopaminergic neurons, in part due to a more
      hyperpolarized GABA(A) reversal potential. The more depolarized GABA(A) reversal
      potential in the dopaminergic neurons is due to the absence of KCC2, the chloride
      transporter responsible for setting up a hyperpolarizing Cl(-) gradient in most
      mature CNS neurons. The data reviewed in this chapter have made it increasingly
      clear that in addition to the effects that nigral GABAergic output neurons have
      on their target nuclei outside of the basal ganglia, local interactions between
      GABAergic projection neurons and dopaminergic neurons are crucially important to
      the functioning of the nigral dopaminergic neurons.

PMID- 17499116
TI  - GABAergic output of the basal ganglia.
AB  - Using GABAergic outputs from the SNr or GP(i), the basal ganglia exert inhibitory
      control over several motor areas in the brainstem which in turn control the
      central pattern generators for the basic motor repertoire including eye-head
      orientation, locomotion, mouth movements, and vocalization. These movements are
      by default kept suppressed by tonic rapid firing of SNr/GP(i) neurons, but can be
      released by a selective removal of the tonic inhibition. Derangement of the
      SNr/GP(i) outputs leads to either an inability to initiate movements (akinesia)
      or an inability to suppress movements (involuntary movements). Although the
      spatio-temporal patterns of individual movements are largely innate and fixed, it
      is essential for survival to select appropriate movements and arrange them in an
      appropriate order depending on the context, and this is what the basal ganglia
      presumably do. To achieve such a goal, however, the basal ganglia need to be
      trained to optimize their outputs with the aid of cortical inputs carrying
      sensorimotor and cognitive information and dopaminergic inputs carrying reward
      related information. The basal ganglia output to the thalamus, which is
      particularly developed in primates, provides the basal ganglia with an advanced
      ability to organize behavior by including the motor skill mechanisms in which new
      movement patterns can be created by practice. To summarize, an essential function
      of the basal ganglia is to select, sort, and integrate innate movements and
      learned movements, together with cognitive and emotional mental operations, to
      achieve purposeful behaviors. Intricate hand-finger movements do not occur in
      isolation; they are always associated with appropriate motor sets, such as eye
      head orientation and posture.

PMID- 17499117
TI  - Localization of GABA receptors in the basal ganglia.
AB  - The majority of neurons in the basal ganglia utilize GABA as their principal
      neurotransmitter and, as a consequence, most basal ganglia neurons receive
      extensive GABAergic inputs derived from multiple sources. In order to understand
      the diverse roles of GABA in the basal ganglia it is necessary to define the
      precise localization of GABA receptors in relation to known neuron subtypes and
      known afferents. In this chapter, we summarize data on the ultrastructural
      localization of ionotropic GABA(A) receptors and metabotropic GABA(B) receptors
      in the basal ganglia. In each of the regions of the basal ganglia that have been
      studied, GABA(A) receptor subunits are located primarily at symmetrical synapses
      formed by GABAergic boutons, where they display a several-hundred-fold enrichment
      over extrasynaptic sites. In contrast, GABA(B) receptors are widely distributed
      at synaptic and extrasynaptic sites on both presynaptic and postsynaptic
      membranes. Presynaptic GABA(B) receptors are localized on striatopallidal,
      striatonigral and pallidonigral afferent terminals, as well as glutamatergic
      terminals derived from the cortex, thalamus and subthalamic nucleus. It is
      concluded that fast GABA transmission mediated by GABA(A) receptors in the basal
      ganglia occurs primarily at synapses whereas GABA transmission mediated by
      GABA(B) receptors is more complex, involving receptors located at presynaptic,
      postsynaptic and extrasynaptic sites.

PMID- 17499118
TI  - Presynaptic modulation of GABA release in the basal ganglia.
AB  - Presynaptic receptors provide plasticity to GABAergic synapses in the basal
      ganglia network, in which GABA neurons outnumber all other neurons. Presynaptic
      receptors, mostly of the metabotropic type, enhance or reduce the strength of
      synaptic inhibition and are activated by ligands being released from the GABA
      terminals themselves (autoreceptors) or by ligands coming from other sources
      (heteroreceptors), including the target neurons innervated by the GABA terminals.
      The latter mechanism, termed retrograde signaling, is given particular emphasis
      as far as it occurs in substantia nigra.

PMID- 17499119
TI  - Development of striatal fast-spiking GABAergic interneurons.
AB  - Fast-spiking GABAergic interneurons represent a very small portion of striatal
      neurons, yet they play a critical role in modulating cortical input and mediating
      inhibition of striatal medium-sized spiny projection neurons. Considering their
      pivotal role in the adult striatum, it is of importance to determine when during
      development these neurons acquire their characteristic properties and function.
      In this review we describe recent work from our laboratories indicating that fast
      spiking GABAergic interneurons are under stronger cortical control than efferent
      neurons at postnatal day 12 but mature considerably between postnatal days 12-19
      in the rat striatum. During this time period, their molecular development is
      under the control of GABAergic and cholinergic mechanisms. Thus, fast-spiking
      interneurons are poised to influence striatal function and perhaps development
      during the postnatal period in rats, and their properties could be influenced by
      commonly used pharmacological agents during a protracted developmental window.
      These findings point to the need for future research to better understand the
      functional maturation of this critical population of striatal GABAergic neurons,
      and the consequences of abnormal maturation of these cells.

PMID- 17499120
TI  - Co-localization of GABA with other neuroactive substances in the basal ganglia.
AB  - The dorsal striatum (caudate putamen) contains two types of GABAergic medium
      spiny neurons (MSNs) that are distinguished by the expression of either the
      opioid peptide, enkephalin, or the opioid peptide, dynorphin, as well as the
      tachykinin substance P. Pharmacological studies suggest that these peptides
      modulate local neurotransmission in the striatum in response to direct and
      indirect dopamine agonists. In contrast, GABA appears to have minimal impact
      within the striatum under these conditions. The actions of the peptide cocktail
      are dependent on the cellular distribution of their receptors in the striatal
      network. The net result of their actions is a homeostatic response that regulates
      striatal output and balances dopamine and glutamate receptor stimulation.

PMID- 17499121
TI  - GABAergic circuits in the basal ganglia and movement disorders.
AB  - GABA is the major inhibitory neurotransmitter in the basal ganglia, and GABAergic
      pathways dominate information processing in most areas of these structures. It is
      therefore not surprising that abnormalities of GABAergic transmission are key
      elements in pathophysiologic models of movement disorders involving the basal
      ganglia. These include hypokinetic diseases such as Parkinson's disease, and
      hyperkinetic diseases, such as Huntington's disease or hemiballism. In this
      chapter, we will briefly review the major anatomic features of the GABAergic
      pathways in the basal ganglia, and then describe in greater detail the changes of
      GABAergic transmission, which are known to occur in movement disorders.

PMID- 17499122
TI  - Simulation of GABA function in the basal ganglia: computational models of
      GABAergic mechanisms in basal ganglia function.
AB  - This chapter outlines current interpretation of computational aspects of
      GABAergic circuits of the striatum. Recent hypotheses and controversial matters
      are reviewed. Quantitative aspects of striatal synaptology relevant to
      computational models are considered, with estimates of the connectivity of the
      spiny projection neurons and fast-spiking interneurons. Against this background,
      insights into the computational properties of inhibitory circuits based on
      analysis and simulation of simple models are discussed. The paper concludes with
      suggestions for further theoretical and experimental studies.

PMID- 17499123
TI  - Frequency of verb use in young children who stutter.
AB  - Several recent studies have suggested that young children who stutter (CWS) tend
      to show depressed lexical performance relative to peers. Given the developmental
      literature as well as several studies of verb processing in individuals who
      stutter, verbs may pose a particular challenge for this group. The purpose of the
      present study was to examine verb use in CWS. In theory, if young CWS differ in
      their production of verbs, this finding would partially explain the findings of
      studies that probed conversational vocabulary skills more generally. Fifteen CWS
      and 15 children who do not stutter (CWNS) participated in a play-based
      conversational sample with a parent. Samples were analyzed for the total number
      of verbs, the number of different verbs, and the proportion of general all
      purpose (GAP) verbs within the samples. CWS produced significantly fewer
      different verbs and total verbs than the CWNS. However, previously reported near
      significant differences in utterance length between groups would appear to temper
      the robustness of this finding. The groups did not differ in the proportion of
      GAP verbs used, suggesting that the CWS did not over-rely on GAP verbs in
      conversational language production but rather used these verbs to the same extent
      as their peers. EDUCATIONAL OBJECTIVES: As a result of this activity, the
      participant will be able to: (1) relate the purpose and rationale for examining
      verb use in children who stutter (CWS); (2) summarize the procedures used to
      assess verb use and GAP verb use in the present study; (3) explain the findings
      of the present study; (4) relate findings to the extant literature on lexical
      diversity in CWS.

PMID- 17499124
TI  - Stages of change and stuttering: a preliminary view.
AB  - As a way to better understand the process of change that occurs in stuttering,
      Craig [Craig, A. (1998). Relapse following treatment for stuttering: a critical
      review and correlative data. Journal of Fluency Disorders, 23, 1-30] compared the
      behavioral changes that people who stutter often experience with and without
      treatment to those that have been observed for certain (non)addictive behavior
      disorders such as smoking, overeating, phobia and anxiety disorder. The process
      underlying these behavioral changes has been described by the transtheoretical or
      "stages of change" model, which is a model of behavior change that can illuminate
      "where" a person is in the process of change, and how this may relate to the
      outcome of either treatment or self-change attempts [Prochaska, J. O., &
      DiClemente, C. C. (1986). The transtheoretical approach. In J. C. Norcross (Ed.),
      Handbook of eclectic psychotherapy. New York: Brunner/Mazel]. The purpose of the
      present study was to analyze the extent to which the responses of adults who
      stutter on a modified Stages of Change Questionnaire yield interrelations among
      questionnaire items that are consistent with a stage-based interpretation.
      Results of both confirmatory and exploratory factor analyses indicated that while
      the modified questionnaire was a relatively good fit for participant responses,
      the structure derived from the exploratory analysis provided a significantly
      better fit to the observed data. Results suggest that a questionnaire
      incorporating items that better reflect the unique behavioral, cognitive and
      affective variables that characterize stuttering may better discriminate stages
      of change in people who stutter as they move through therapy, or are engaged in
      self-directed change. EDUCATIONAL OBJECTIVES: After reading this paper, the
      learner will be able to: (1) describe the transtheoretical or "stages of change"
      model; (2) describe the various processes that are associated with different
      stages of change; (3) summarize research findings in stages of change as they
      apply to a variety of clinical populations; (4) discuss the applicability of the
      findings from the present study to stuttering treatment, and (5) relate
      conventional strategies and techniques used in stuttering therapy to different
      stages in the process of change.

PMID- 17499125
TI  - Enhancing treatment for school-age children who stutter I. Reducing negative
      reactions through desensitization and cognitive restructuring.
AB  - This paper describes several treatment strategies that clinicians can use to
      address negative affective, behavioral, and cognitive reactions that school-age
      children who stutter may experience as part of their disorder. Specific
      strategies include desensitization to stuttering, cognitive restructuring, self
      acceptance, purposeful self-disclosure, and a combination of both fluency
      enhancing and stuttering modification approaches. To facilitate clinicians'
      application of these techniques, the strategies are presented in the context of a
      case study involving a 9-year-old boy who participated in a comprehensive
      treatment program for stuttering. Following treatment, the child exhibited
      improved communication attitudes and a reduced frequency and severity of
      stuttering, combined with reduced concern about stuttering, as indicated through
      formal and informal assessments. Findings suggest that clinicians can help
      children overcome the negative reactions associated with stuttering through a
      number of treatment strategies that can be applied in a variety of clinical
      settings. EDUCATIONAL OBJECTIVES: After reading this article, participants will
      be able to: (1) define desensitization and cognitive restructuring and provide
      two arguments in favor of using these strategies in treatment for school-age
      children who stutter; (2) describe two treatment strategies for helping school
      age children achieve desensitization through stuttering therapy; (3) describe two
      treatment strategies for helping school-age children engage in cognitive
      restructuring in the context of therapy.

PMID- 17499126
TI  - Enhancing treatment for school-age children who stutter II. Reducing bullying
      through role-playing and self-disclosure.
AB  - This paper describes several treatment strategies that clinicians can use to help
      children who stutter who are experiencing bullying and other negative reactions
      from their peers. Specific strategies include problem-solving activities designed
      to help the child develop appropriate responses to bullying and a classroom
      presentation designed to educate peers about stuttering. To facilitate
      clinicians' application of these techniques, the strategies are presented in the
      context of a case study involving a 9-year-old boy who participated in a
      comprehensive treatment program for stuttering. Following treatment, the child
      exhibited an increased ability to respond to bullying experiences in a
      constructive fashion. In addition, negative comments by the child's peers
      diminished following the classroom presentation. Findings suggest that clinicians
      can help children overcome bullying and other negative reactions associated with
      stuttering through a number of well-supported treatment strategies that can be
      applied in a variety of clinical settings. EDUCATIONAL OBJECTIVES: After reading
      this article, participants will be able to: (1) define bullying and teasing and
      explain the difference between the two experiences; (2) describe two strategies
      for helping children who stutter successfully manage bullying experiences at
      school and in other settings; and (3) explain two strategies for educating
      children about stuttering and about bullying.

PMID- 17499127
TI  - Presentation and management of extensive fronto-orbital-ethmoid mucoceles.
AB  - OBJECTIVES: The aim of the study was to report the presentation and management of
      extensive fronto-orbital-ethmoid (FOE) mucoceles. METHODS: This study is a
      retrospective chart review of 13 consecutive patients requiring surgical
      intervention for extensive FOE mucoceles. Patients were treated over the period
      from 1999 to 2003. Variables examined include chief complaint, risk factors,
      location of erosion, management, and complications. Follow-up ranged from 12 to
      36 months. RESULTS: Most common chief complaint was eye proptosis, followed by
      forehead swelling and orbital cellulitis. Four patients had previous functional
      endoscopic sinus surgery (FESS) and another 4 patients had history of prior
      trauma and frontal sinus obliteration. Eleven patients had skull base erosion and
      12 had orbital wall erosion. Four patients were managed endoscopically. Of these,
      1 had previously undergone FESS, whereas the other 3 had no risk factors. All
      patients with prior trauma/obliteration were treated with coronal flap and
      frontal sinus obliteration. One patient who had undergone 2 previous FESS was
      successfully treated with coronal flap without obliteration. One patient treated
      with an osteoplastic flap had cerebrospinal fluid leak that was identified and
      repaired intraoperatively with a pericranial flap. CONCLUSION: Extensive FOE
      mucoceles can be successfully and safely treated by endoscopic and non-endoscopic
      methods. The choice of surgical approach mainly depends on the anatomy of the
      frontal recess. Prior trauma and FESS are associated with requiring coronal flap
      and frontal sinus obliteration.

PMID- 17499128
TI  - The role of allergic rhinitis in the development of otitis media with effusion:
      effect on eustachian tube function.
AB  - PURPOSE: The pathogenesis of otitis media with effusion (OME) is considered
      multifactorial, with viral upper respiratory tract infection and eustachian tube
      dysfunction. Allergy may be related to the pathogenesis of OME or to another
      etiological factor. We investigated the role of allergic rhinitis (AR) in
      children with OME and evaluated eustachian tube function in patients with AR.
      MATERIALS AND METHODS: We prospectively analyzed the prevalence of AR, serum
      eosinophil count, and serum total IgE concentrations in 123 children with OME and
      in 141 controls. IgE concentration in middle ear effusion was compared in
      children with OME with and without AR, and eustachian tube function after a nasal
      provocation test was compared between patients with AR and controls. RESULTS: The
      prevalence of AR in children with OME (28.4%) and control subjects (24.1%) did
      not differ significantly. These 2 groups also showed no differences in total
      eosinophil count and serum and middle ear effusion IgE concentration.
      Abnormalities in eustachian tube function were the same in patients with AR and
      controls. CONCLUSIONS: Allergic rhinitis may not be related to the development of
      OME in children.

PMID- 17499129
TI  - Positron emission tomography: poor sensitivity for occult tonsillar cancer.
AB  - PURPOSE: The aim of the study was to determine the sensitivity of preoperative
      positron emission tomography (PET) scans in the detection of primary tumors of
      the tonsils. MATERIALS AND METHODS: We conducted a retrospective review of 46
      patients treated at a university medical center for occult tonsillar cancer
      during the years 2002 to 2004. We identified patients who underwent a
      preoperative PET scan to locate an unknown primary tumor. Fusion computed
      tomography with PET (PET/CT) was used to further delineate anatomic localization
      to the tonsil area. A positive PET/CT scan was defined as asymmetric increased
      tracer uptake in the tonsil and/or tonsillar fossa ipsilateral to the tonsillar
      cancer site when compared with the contralateral site. A negative PET/CT scan was
      defined as equivocal symmetric tracer uptake bilaterally. RESULTS: Of the 46
      patients, 6 (13.0%) had pretreatment PET scans. Of these 6 patients, 16.7% (n =
      1) had positive PET, 66.7% (n = 4) had negative PET, and 16.7% (n = 1)
      demonstrated increased tracer uptake in tonsils bilaterally greater on the side
      contralateral to the cancer. In this group, PET scans had a sensitivity of 0.167
      and false-negative ratio of 0.667 for tonsillar cancer detection. CONCLUSIONS:
      Although the patient population in this study is small (n = 6), the findings
      suggest that PET/ CT scans may offer a low sensitivity in detection of primary
      tonsillar cancers. However, PET/CT scans still have a significant role in the
      detection of other unknown primary head and neck tumors. Technical reasons for
      this finding are discussed.

PMID- 17499130
TI  - Osteonecrosis of the jaws due to bisphosphonate use. A review of 60 cases and
      treatment proposals.
AB  - PURPOSE: Bisphosphonates are compounds used in the treatment of various metabolic
      and malignant bone diseases. In the last two and a half years, there has been a
      striking increased referral of patients with exposed necrotic jawbone, mostly
      after several teeth extractions. The only clinical feature common in all patients
      was the use of bisphosphonates in the treatment of bone diseases. PATIENTS AND
      METHODS: We performed a retrospective multicentric study of 60 patients with
      necrotic bone lesions of the jaws of various extent from July 2003 to October
      2005. The necrotic bone involved the maxilla (37%), the mandible (50%), or both
      (13%). The bisphosphonate administered was mostly zoledronate. The management of
      the patients included cessation of bisphosphonate therapy for more than 6 months,
      long-term antibiotics, hyperbaric oxygen administration in some cases, and
      various surgical restorative procedures. RESULTS: The implementation of the
      treatment protocol in 7 patients so far lead to high cure rates, whereas surgical
      restoration of the defect without previous cessation of bisphosphonate therapy
      had discouraging results. CONCLUSIONS: Clinicians and dentists should have in
      mind this new complication of bisphosphonate administration to identify and treat
      osteonecrosis of the jaws.

PMID- 17499132
TI  - Peri- and postoperative complications after laser surgery of tumors of the upper
      aerodigestive tract.
AB  - BACKGROUND: Because of the increasing use of laser surgery for tumors of the
      upper aerodigestive tract, there is also a discussion in peri- and postoperative
      complications of this kind of surgery. It was the aim of the present
      investigation, based on a great number of treated patients, to point out the
      complications of laser surgery and give a hint for possible dangers. PATIENTS AND
      METHODS: Altogether, 1528 patients suffering from tumors of the upper
      aerodigestive tract were investigated. The peri- and postoperative complications
      were assumed in respect to localization and stage of tumor. RESULTS: The
      different evidence of complications depended on the localization and stage of
      tumor. It was pointed out that postoperative bleeding is the main complication
      after laser surgery of tumors of the upper aerodigestive tract. Overall, there
      were low complication rates especially after surgery of glottic carcinomas in
      early stages. CONCLUSIONS: Peri- and postoperative complications after laser
      surgery of tumors of the upper aerodigestive tract are relatively seldom events.
      Because of the fact that postoperative bleeding is the most common complication,
      every clinic that performs laser surgery should have a clear concept of
      management for this complication. Also, strategies to avoid these complications
      should be developed.

PMID- 17499131
TI  - Titanium middle ear prostheses in staged ossiculoplasty: does mass really matter?
AB  - OBJECTIVES: Several articles have demonstrated the efficacy of titanium middle
      ear prostheses. Our study compares the results of 2 brands of titanium implants
      that differ in design and weight to assess potential benefit of one over the
      other. The purpose of this study was to investigate the relationship of
      prostheses mass based on the stiffness vs mass curve of acoustic transfer between
      2 different brands of titanium implants. STUDY DESIGN: A retrospective study was
      done for this article. METHODS: A chart review was conducted including the
      postoperative results, complications, and audiometric data for 34 patients with
      titanium middle ear implants (21 Tuebingen VARIO prostheses [Kurz Co, DuBlingen,
      Germany] and 13 Micron Monolithic prostheses [Gyrus ENT, Bartlett, TN]) with an
      average follow-up of 19 months. Both total and partial prostheses were included.
      Average postoperative air-bone gap (ABG) and average improvement in ABG was
      compared between the groups. RESULTS: There was a considerable variability in the
      postoperative results with both implants. Both the Kurz prostheses (group A) and
      the Gyrus prostheses (group B) demonstrated an average postoperative ABG of less
      than 25 dB (23.2 and 21.3 dB). There was no significant difference between the
      groups. Both groups also demonstrated an improvement in average ABG (preoperative
      minus postoperative ABG), 9.6 and 11.2 dB. There was no significant difference
      between the 2 prosthesis types in the frequency-specific ABG (500, 1000, 2000,
      and 4000 Hz). Both groups demonstrated maximal resonant frequency at 2000 Hz. The
      extrusion rates (5% and 8%) were comparable between the groups. CONCLUSION:
      Factors other than the prosthesis design (eg, surgical technique, fibrosis,
      retraction, and cholesteatoma) primarily determine hearing results after staged
      ossiculoplasty. The differences we noted in frequency-specific hearing
      improvement do not demonstrate that the mass of the prostheses plays a
      significant role in outcome.

PMID- 17499133
TI  - The comparison of tonsillar surface and core cultures in recurrent tonsillitis.
AB  - OBJECTIVE: This study was conducted to investigate whether there is any
      difference between tonsillar surface and deep tissue cultures in patients who
      underwent tonsillectomy for recurrent tonsillitis. METHODS: Tonsillar surface and
      core tonsillar cultures were taken in all patients. The samples were inoculated
      into 5% sheep blood, chocolate, and MacConkey agar. The bacteria isolated were
      identified by using standard methods as well as API kits (Bio Merieux) if
      necessary. RESULTS: Pathogenic bacteria were isolated in 77 patients, and no
      pathogenic bacteria were recovered in 39 of 116 patients included in the study.
      Of these 77 patients, in 52 patients, different types of bacteria were recovered
      from the surface and deep tissue cultures, whereas in 25 patients, the same types
      of bacteria were isolated from both surface and deep tissue cultures. The
      estimated probabilities of tonsillar bacteriology via surface swabs for
      Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, and
      group A beta-hemolytic streptococci were 27.2%, 38.4%, 66.6%. and 62.5%,
      respectively. H influenzae was less frequently predicted by surface culture than
      others. CONCLUSIONS: We think that the swab cultures taken from the tonsillar
      surface may not always reveal the real pathogen of the tonsils. In addition, the
      estimated probability of tonsillar bacteriology by surface swabs varies with the
      type of the pathogen. If medical therapy is planned on the basis of the tonsillar
      surface culture, then antibiotics also effective against H influenzae besides the
      target microorganisms may be chosen.

PMID- 17499134
TI  - Huge teratoma of the nasopharynx.
AB  - Congenital immature teratoma of the nasopharynx is a very rare form of
      extragonadal teratoma. In this article, management of a newborn with
      nasopharyngeal teratoma who underwent tumor resection is reported. The tumor,
      which originated from the nasopharynx, almost filled the oral cavity and
      protruded through the mouth, with its external part comparable to the size of the
      head. She could breath when the head and mass were turned to the left. For safe
      management of these cases, prenatal evaluation, careful preoperative assessment
      of the airway, sufficient preparation, and intubation by an expert are mandatory.
      Perioperative bleeding and obstruction of airway by the tumor or its remnant
      could render the case difficult.

PMID- 17499135
TI  - Cavernous hemangioma of the tympanic membrane and external ear canal.
AB  - OBJECTIVES: The aims of this study are to document the occurrence of a cavernous
      hemangioma of the tympanic membrane (TM) and external auditory canal (EAC) that
      invaded the middle ear spaces and to review the relevant literature. METHODS: The
      clinical presentation, imaging studies, operative report, and histologic findings
      of this new case of cavernous hemangioma are reviewed. RESULTS: A cavernous
      hemangioma of the TM and EAC involving the middle ear spaces was surgically
      excised without complications. The pulsatile tinnitus, which affected our patient
      at the same ear where the lesion was situated, disappeared after surgery. Our
      case represents the first documented cavernous hemangioma of the TM and EAC that
      invaded the middle ear spaces and the eighth case of cavernous hemangioma of the
      EAC/TM. Computed tomography is the method of choice in evaluating this lesion.
      CONCLUSIONS: Hemangiomas of the EAC and/or TM are extremely rare entities
      amenable to surgical excision. With magnetic resonance imaging, there is
      difficulty in defining the exact location of the tumor and degree of soft tissue
      involvement.

PMID- 17499136
TI  - Bilateral atresia of the submandibular duct orifices.
AB  - Atresia of the submandibular duct orifice is a rare developmental anomaly. Early
      identification and treatment of atresia of the submandibular duct orifice prevent
      feeding and breathing difficulties, dilatation of the submandibular duct,
      submandibular gland infection, or pressure atrophy. Imperforate submandibular
      duct should be distinguished from duplication abnormalities of the duct and other
      cystic lesions in the floor of the mouth. To date, magnetic resonance imaging
      findings of the atresia of the submandibular duct orifice have not been reported.
      The aim of this study was to describe clinical and radiologic evaluation of an
      infant with atresia of the bilateral submandibular duct orifices.

PMID- 17499137
TI  - Otitic hydrocephalus: case report and literature review.
AB  - Otitic hydrocephalus is characterized by elevated intracranial pressure without
      focal neurologic abnormalities. The pathogenesis of otitic hydrocephalus remains
      unclear, but it usually occurs secondary to lateral sinus thrombosis. With the
      advent of new antibiotics, there has been a spectacular decrease in the
      complications of otitis media. Otogenic intracranial hypertension, always an
      uncommon condition, is seen only very rarely nowadays. Here we present a case of
      otitic hydrocephalus and discuss about its pathophysiology, clinical findings,
      and treatment.

PMID- 17499138
TI  - A forgotten gauze pack in the nasopharynx: an unfortunate complication of
      adenotonsillectomy.
AB  - A case of a foreign body lodged in the nasopharynx for a long time as a
      complication of adenotonsillectomy is presented. The patient was an 11-year-old
      boy admitted with nasal obstruction and bilateral foul-smelling purulent
      rhinorrhea. The diagnosis was confirmed with nasal endoscopy. Immediate removal
      of foreign body in the nasopharynx was performed under general anesthesia.
      Although foreign bodies lodged into the nasopharynx are rare, they may cause
      serious and even fatal complications. A high index of suspicion, particularly for
      persistent symptoms, is essential and necessitates further investigation before
      diagnosis of a case of rhinosinusitis or empirically prescribing antibiotics.

PMID- 17499139
TI  - A nearly circumferential hyoid bone.

PMID- 17499140
TI  - Primary olfactory neuroblastoma originating from the inferior meatus of the nasal
      cavity.
AB  - Olfactory neuroblastoma is a rare malignant tumor of the nasal cavity arising
      from the olfactory neuroepithelium. It usually presents as a polypoid mass high
      in the nasal vault including the cribriform plate, superior turbinate, and
      superior portion of nasal septum. An 89-year-old man visited our office with
      symptoms of occasional left nasal bleeding and obstruction. On the endoscopic
      examinations, polypoid mass with bleeding tendency was observed in the left
      inferior meatus. Biopsy was performed, and the diagnosis of olfactory
      neuroblastoma was confirmed by histopathologic examination and
      immunohistochemical staining. The tumor was resected via medial maxillectomy, and
      the final pathologic report established that it was primary olfactory
      neuroblastoma that occurred from the inferior meatus. In this report, a
      literature review was performed on the pathologic characteristics and prognosis
      of the tumor, and possible hypotheses that olfactory neuroblastoma has originated
      from the inferior meatus were discussed.

PMID- 17499141
TI  - Intraglandular toxoplasmosis of the parotid gland pre- or postoperative
      diagnosis?
AB  - Toxoplasmosis is an ubiquitous protozoan infection, caused by the coccidian
      Toxoplasma gondii. It usually presents clinically with lymphadenopathy, mainly in
      the head and neck region. However, in the English literature, very scarce cases
      of intraparotid Toxoplasma exist, none having been diagnosed preoperatively. In
      this article, we present 2 cases of intraglandular parotid toxoplasmosis, one
      diagnosed postoperatively and the other preoperatively. We also review the
      relevant literature concerning Toxoplasma infection of the parotid gland.

PMID- 17499142
TI  - Primary hydatid cyst of the neck.
AB  - Hydatid cyst in the head and neck is very rare even in countries where
      echinococcus infestation is endemic. We report the case of a 33-year-old female
      patient presenting with a hydatid cyst in the lateral cervical region. The
      diagnosis of hydatid cyst is made mainly with the help of imaging methods and
      review of the patient's history. Serologic tests can also be useful. The
      diagnostic use of fine-needle aspiration biopsy generally has not been advised
      because of the potential to precipitate acute anaphylaxis or to spread daughter
      cysts. Treatment is surgical. Postoperative albendazole therapy is suggested
      especially when there is preoperative contamination risk.

PMID- 17499143
TI  - Localized amyloidosis masquerading as nasopharyngeal tumor: a review.
AB  - Amyloidosis comprises a diverse collection of disease characterized by the
      presence of amorphous extracellular eosinophilic deposits of unique protein
      fibrils that gives apple green birefringence under polarized light after staining
      with Congo red. Head and neck region is the commonest site for localized form of
      amyloidosis. We report a case of a 43-year-old man with localized amyloidosis of
      nasopharynx with oropharyngeal extension and its management, along with a review
      of relevant literatures.

PMID- 17499144
TI  - Bilateral aberrant internal carotid arteries: treatment of a hemorrhagic
      complication.
AB  - The aberrant internal carotid artery is a rare congenital abnormality that may
      present with pulsatile hemorrhage if undiagnosed before surgical intervention in
      the middle ear. We present such a patient who was treated successfully with
      endovascular sacrifice of one of her bilateral lesions after recurrent episodes
      of pulsatile hemorrhage complicating multiple tympanostomy tube revisions.

PMID- 17499145
TI  - Collision tumor of thyroid: metastatic lung adenocarcinoma plus papillary thyroid
      carcinoma.
AB  - Collision tumors are rare entities wherein 2 separate, distinct histologic
      malignant neoplasms occur in adjacent anatomic proximity. The 2 malignancies may
      originate from the same organ or occur as metastases from other sites. We present
      a case of a collision tumor of metastatic lung adenocarcinoma and papillary
      thyroid carcinoma occurring in the thyroid gland of a 63-year-old woman who
      presented with a multinodular central neck mass. After excision and
      histopathologic examination, this tumor was identified as a collision tumor. This
      is the first report of this unique combination of tumors occurring in the thyroid
      gland. This case report emphasizes the role of detailed histopathologic analysis
      and the use of immunohistochemistry in better identifying rare thyroid neoplasms.

PMID- 17499146
TI  - Assessment of bioavailability and risk of iron in phytomedicines Aconitum
      carmichaeli and Paeonia lactiflora.
AB  - Since n-octanol, a long-chain alkanol, presents a configuration similar to that
      of carbohydrates and lipids, the lipophilicity and absorptivity of organic
      medicines may be assessed from their distribution coefficients between octanol
      and water. n-octanol is used as a model of biomembrane. This strategy has been
      used in order to define the species of iron in two phytomedicines and to study
      the distribution of iron in decoctions of phytomedicines in the stomach and the
      intestine. The concentrations of iron in the original herbal materials and in n
      octanol- and water-soluble species were determined by flame atomic spectrometry
      following mixed acid digestion. The acidities of digestive and absorptive juices
      (saliva, gastric juice, bile and intestine), the phytomedical composition and the
      compatibility of phytomedicines, i.e., the combination ratio of single
      phytomedicines, greatly affected the iron complexing ligands and determined the
      species and bioavailability of iron. The concentration of octanol-soluble iron
      could be used for the bioavailability assessment of iron in phytomedicines. The
      dosage of iron in phytomedicines could be designed according to the level of the
      octanol-soluble iron and the reference daily intakes for iron (18 mg/d). Risk
      assessment could be examined through the comparison between the level of the
      octanol-soluble iron and the tolerable upper intake level for iron (45 mg
      iron/d).

PMID- 17499147
TI  - Effect of zinc ion on the osteogenic and adipogenic differentiation of mouse
      primary bone marrow stromal cells and the adipocytic trans-differentiation of
      mouse primary osteoblasts.
AB  - A series of experimental methods including 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) test, alkaline phosphatase (ALP) activity
      measurement and Oil Red O stain and measurement were employed to assess the
      effect of zinc ion on the osteogenic and adipogenic differentiation of mouse
      primary bone marrow stromal cells (MSCs) and the adipogenic trans-differentiation
      of mouse primary osteoblasts. The results showed that except for individual
      concentrations of zinc ion there was no effect on the proliferation of MSCs and
      osteoblasts. Zinc ion inhibited the osteogenic differentiation of MSCs at all the
      concentrations tested. It also inhibited adipogenic differentiation at all
      concentrations tested except 10(-9)mol/L. Both of the inhibition effects were
      attenuated with time increasing. Zinc ion depressed adipocytic trans
      differentiation of osteoblasts at concentrations of 10(-11) and 10(-10)mol/L, but
      the effect could be reversed to promote or even be removed when concentration was
      increased. It suggests that the influence of zinc ion on osteogenic, adipogenic
      differentiation of MSCs and adipocytic trans-differentiation of osteoblasts
      depends on zinc ion concentrations and incubation time. The protective effects of
      zinc ion on bone may be mediated by modulating differentiation of MSCs away from
      the adipocytes and inhibiting adipocytic trans-differentiation of osteoblasts.
      This may in turn promote osteoblast formation and reduce secretion of cytokines
      which may inhibit osteoclast formation and activation. These findings may be
      valuable for better understanding the mechanism of the effect of zinc ion on
      bone.

PMID- 17499148
TI  - Substantivity of zinc salts used as rinsing solutions and their effect on the
      inhibition of Streptococcus mutans.
AB  - The antimicrobial efficacy of zinc (Zn) salts (sulfate and acetate) against
      Streptococcus mutans (S. mutans) present in the oral cavity was tested in this
      study. The substantivity of Zn salts was assessed by determining the
      concentration of Zn in whole, unstimulated saliva and by measuring the magnitude
      of suppression of salivary S. mutans, 2h after rinsing. The concentration of Zn
      was measured by atomic absorption spectrometry (AAS) with electrothermal
      atomization (ET AAS) in saliva sampled before (basal) and 24h after mouth rinsing
      with different concentrations of Zn (0.1%, 0.5% and 1%) administrated as sulfate
      and acetate. The estimation of Zn levels in samples collected 30, 60, 90 and 120
      min after rinsing was carried out by AAS with flame atomization (FAAS).
      Immediately after rinsing, the concentration of Zn in saliva sharply increased
      with respect to the baseline values (0.055+/-0.017 mg/L), followed by a sustained
      decrease, probably due to clearance of salivary flow or swallowing during
      sampling. A significant reduction (>87%) in the total mean S. mutans counts was
      found 2h after rinsing either with sulfate or acetate solutions, as evidence of
      the high substantivity and effectiveness of the Zn salts tested. A statistically
      significant inverse relationship (p<0.001 and the Pearson correlation
      coefficients between -34% and -50%) was found between Zn levels and the
      respective pH values measured in the samples collected 60 and 120 min after
      rinsing, sustaining the theory of bacterial glycolysis inhibition.

PMID- 17499149
TI  - Alterations of trace elements (Zn, Se, Cu, Fe) and related metalloenzymes in
      rabbit blood after severe trauma.
AB  - To investigate the status of the trace elements (TEs) and related metalloenzymes
      activities in the injury and repair process after severe trauma, we established a
      rabbit model of severe trauma whose Injury Severity Score (ISS) was 22.
      Concentrations of blood selenium (Se) and serum copper (Cu), zinc (Zn), iron
      (Fe), and ferritin were measured on D0 (before injury), and day (D) 1, D2, D3,
      D6, D9, D14, D21, D28 after trauma, respectively. The activities of glutathione
      peroxidase (GPx), Cu/Zn superoxide dismutase (Cu/Zn-SOD), myeloperoxidase (MPO),
      the contents of lipid peroxidation product malondialdehyde (MDA) and serum
      biochemical profile were detected synchronously. In addition, the morphologic
      changes of major organs were observed at different time intervals. Results showed
      that blood Se and serum Zn, Fe contents decreased significantly within 2 weeks
      after injury. Serum Cu concentration was significantly reduced on D1 but
      normalized quickly. Serum ferritin level increased during the first week while
      following an obvious decrease thereafter. The blood GPx activity dropped markedly
      from D1 to D6, the serum Cu/Zn-SOD activity decreased on D1 and then increased
      significantly within 2 weeks, and the blood MPO-positive stained cells increased
      within a week after trauma and followed by a decrease from D14 to D21. The serum
      MDA increased significantly on D6. Seven of 34 rabbits died in 4-6 days after
      injury. Biochemistry values and pathological features revealed these rabbits died
      of multiple organ dysfunction syndrome (MODS). Our experiment suggested that the
      circulating TEs status is dramatically modified in response to trauma, which
      might be a factor in MODS.

PMID- 17499150
TI  - Oxidant and antioxidant status of Turkish marasmic children: a single center
      study.
AB  - The aim of this study was to investigate plasma oxidant and antioxidant status in
      Turkish marasmic children. The study population consisted of 38 marasmic children
      (group I) and 28 age-matched children (group II) who were apparently well, with
      weight-forage >80% of the standards in the same region. After overnight fasting,
      venous blood samples were drawn and immediately transferred to heparinized and
      normal tubes. Plasma antioxidant potential (AOP), and malondialdehyde (MDA)
      levels were measured in both groups. The plasma MDA levels were found to be
      higher in group I than in group II. However, plasma AOP values were lower in
      group I than in group II. The present study suggests that AOP is reduced due to
      an impaired antioxidant system in the plasma of malnourished patients. This
      oxidant stress causes significant peroxidation. Also, the antioxidant defense
      system of the patients is deteriorated in marasmus.

PMID- 17499151
TI  - Comparison of the effects of zinc alone and zinc associated with selenium and
      vitamin E on insulin sensitivity and oxidative stress in high-fructose-fed rats.
AB  - PURPOSE: In the present study, we investigated the effect of an association of
      micronutrients (zinc (Zn), selenium (Se) and vitamin E (vit E)) on insulin
      activity and antioxidant status in an animal model of insulin resistance, the
      high-fructose-fed rat. PROCEDURES: Five experimental groups were compared: a
      control group (C) receiving a standard diet, a high-fructose-fed group (F) where
      58% of the diet carbohydrate was fructose, a high-fructose-fed group supplemented
      with Zn alone (FZn group), a high-fructose-fed group supplemented micronutrients
      (Zn, Se and vit E) (FMicro group). A fifth group consumed a high-fructose diet
      and received metformin in the drinking water (200mg/day/rat) (FMet group).
      Insulin sensitivity was measured using the euglycemic hyperinsulinic glucose
      clamp technique. Metabolic parameters, trace elements and antioxidant parameters
      were measured in blood samples from all groups. RESULTS: High-fructose-fed rats
      were resistant to insulin as indicated by the lower glucose infusion rate. The
      insulin sensitivity of FZn, FMicro and FMet groups was higher than that of F
      group, with the highest insulin sensitivity for the FMicro group. No
      statistically significant difference in glycemia between the groups was observed.
      The ratio of reduced to oxidized glutathione was higher in FZn and FMicro groups
      than in all other groups, as a consequence of decreased oxidized glutathione.
      CONCLUSION: Our results provide direct evidence that micronutrients have a
      beneficial effect on insulin sensitivity and some components of the antioxidant
      defense system in an animal model of insulin resistance.

PMID- 17499152
TI  - Comparison of acute absorption of commercially available chromium supplements.
AB  - Chromium (Cr) supplements are available as picolinate, nicotinate or chloride
      (the latter primarily in multivitamin-mineral supplements). The picolinate form
      has been reported to be the best absorbed and most efficacious, but some reports
      question which form has superior absorption. The present study examined acute Cr
      absorption, based on 24h urinary Cr values, for picolinate, two types of
      nicotinate, and chloride in young adult, non-overweight females. College-aged
      women were given 200 microg of Cr as each of the four supplement types in random
      order accompanied by a small standardized meal, separated by at least a week
      washout. Cr picolinate produced significantly higher 24h urinary Cr than either
      of two nicotinate supplements or Cr chloride given in a multivitamin-mineral
      supplement. This difference was seen for absolute values of the urinary Cr and
      for percent increases. In conclusion, based on an indirect measure of acute
      absorption, Cr picolinate was superior to three other Cr complexes commonly sold
      as supplements.

PMID- 17499153
TI  - Role of Zn2+ in epigallocatechin gallate affecting the growth of PC-3 cells.
AB  - Green tea has chemo-preventive effects to human carcinoma including prostate
      cancer. Epigallocatechin gallate (EGCG) is the major active component in green
      tea. Zn(2+) is indispensable to our health, and plays an important role in the
      normal function and pathology of the prostate gland, and might be a good marker
      for diagnosing prostate cancer. Effects of Zn(2+), EGCG and their interactions on
      the growth of androgen-insensitive prostate cancer cell (PC-3) were investigated
      in the present paper. The results show that Zn(2+) and EGCG inhibited the growth
      of PC-3 cells in a time- and dose-dependent manner, but effects of interactions
      of EGCG with Zn(2+) were extremely dependent on their concentrations and added
      orders. Inhibitory effects of Zn(2+) were significantly decreased in the presence
      of EGCG on PC-3 cell growth. Therefore, we hypothesize that complexation of EGCG
      with Zn(2+) might be responsible for the observed decrease of the bioactivities
      of Zn(2+) against PC-3 cells.

PMID- 17499154
TI  - The effect of chronic cadmium exposure on the pharmacokinetics of theophylline
      and ciprofloxacin in rats.
AB  - Cadmium has been associated with a number of adverse health effects but the
      impact of those effects on the pharmacokinetics of different drugs has not been
      investigated. Therefore, the pharmacokinetics of theophylline and ciprofloxacin
      were studied in cadmium-exposed and control rats (72 rats) following i.p.
      (6.5mg/kg) and p.o. (10mg/kg) administration, respectively. The third-generation
      offsprings of rats exposed to 100 microg/mL of cadmium chloride in drinking water
      were used in this study. Following 8 weeks of exposure, animals received the
      drugs as a single dose. Blood samples were withdrawn at different time-points and
      the plasma concentrations of both drugs were analyzed by HPLC. The
      pharmacokinetic parameters of theophylline and ciprofloxacin were altered
      significantly in the cadmium-exposed animals. For theophylline, a statistically
      significant increase (p<0.0001) in C(max) (69%) and AUC(0-)(infinity) (68%) of
      theophylline in the cadmium-exposed rats as compared to the control were
      observed. A corresponding significant (p<0.0001) reduction of 41% in clearance
      (CL/F) of theophylline was detected in the exposed group. Neither the half-life
      nor the mean residence time (MRT) showed any significant change due to the
      exposure to cadmium. For ciprofloxacin, no significant difference was seen in the
      C(max) of the exposed group as compared to the control animals. However, a delay
      in T(max) was observed in the exposed group (from 0.16(+/-0.003) to 0.37(+/
      0.14)h). A small, but significant increase in t(1/2) (p<0.05) was detected
      (1.74(+/-0.25) vs. 1.45(+/-0.12)h). A significant reduction (p<0.05) of CL/F from
      30.54(+/-1.9) to 24.01(+/-3.81)mL/min/kg was seen in the treated group. The
      current investigation showed that chronic exposure to cadmium could have a very
      significant impact on altering the pharmacokinetic parameters of various drugs.
      Therefore, in cadmium-polluted areas, dose adjustments and drug monitoring,
      especially for drugs with a narrow therapeutic window, should be carried out.

PMID- 17499155
TI  - Stable isotope pilot study of exchangeable copper kinetics in human blood plasma.
AB  - To develop further our understanding of initial dietary copper metabolism, a
      method has been developed to separate plasma copper that is bound to albumin,
      from that bound to ceruloplasmin. This method has been tested using plasma
      samples from a pilot study involving six human volunteers who consumed 3mg oral
      doses of the stable isotope (65)Cu and gave blood samples at timed intervals up
      to 7 days. The results suggest that this method can be used to monitor dynamic
      fluctuations in newly absorbed copper over a short time frame.

PMID- 17499156
TI  - Raised serum copper results does not mean excess body copper.

PMID- 17499157
TI  - Introduction: higher motor cognition - from basic neuroscience to apraxia.

PMID- 17499158
TI  - Neural representations of pantomimed and actual tool use: evidence from an event
      related fMRI study.
AB  - Pantomime of tool use is a highly sensitive test to detect apraxia. The
      relationship to real-life performance is however unclear since apraxic patients
      frequently improve substantially when allowed to actually use tools. In the
      present study, the neural correlates of pantomimed and actual tool use were
      directly compared in healthy subjects using an event-related functional magnetic
      resonance imaging (fMRI) paradigm. Subjects were requested to demonstrate the use
      of various tools either as pantomimes or with the tool in hand. Movement and pre
      movement events were evaluated. The comparison of all conditions versus rest
      revealed a widespread activation including parietal, posterior temporal, frontal,
      and subcortical areas with some characteristic activation for the different
      events. The direct comparison between pantomime and actual use conditions
      revealed no or only minor differential activations for pre-movement events.
      During the movement event, actual tool use induced the expected additional
      activation in sensory and motor areas, but also representations presumably
      related to tool-use knowledge at parietal, posterior temporal, and frontal sites.
      The opposite contrast of pantomimed versus actual tool use revealed differential
      activation only in the left intraparietal sulcus in a corresponding region-of
      interest analysis. We conclude that planning and preparing of either pantomimed
      or actual tool use share large parts of a common network. Characteristic
      differences in the kinematics and dynamics of both movement conditions may be
      defined just before or during the initiation of the movement when sensory cues
      about the tool and environment are available in the actual use condition. Sensory
      and cognitive cues may provide apraxic patients the capacity to evoke a correct
      action program despite impaired pantomime.

PMID- 17499159
TI  - The neural basis for understanding non-intended actions.
AB  - We can often understand when actions done by others do or do not reflect their
      intentions. To investigate the neural basis of this capacity we carried out an
      fMRI study in which volunteers were presented with video-clips showing actions
      that did reflect the intention of the agent (intended actions) and actions that
      did not (non-intended actions). Observation of both types of actions activated a
      common set of areas including the inferior parietal lobule, the lateral premotor
      cortex and mesial premotor areas. The contrast non-intended vs. intended actions
      showed activation in the right temporo-parietal junction, left supramarginal
      gyrus, and mesial prefrontal cortex. The converse contrast did not show any
      activation. We conclude that our capacity to understand non intended actions is
      based on the activation of areas signaling unexpected events in spatial and
      temporal domains, in addition to the activity of the mirror neuron system. The
      concomitant activation of mesial prefrontal areas, known to be involved in self
      referential processing, might reflect how deeply participants are involved in the
      observed scenes.

PMID- 17499160
TI  - Stimulus properties matter more than perspective: an fMRI study of mental imagery
      and silent reading of action phrases.
AB  - The role of the primary motor cortex (M1) in tasks involving action words remains
      controversial. Therefore, we investigated whether the previously reported
      involvement of M1 in processing of action words results from the semantic
      representation of action words per se, or if M1 activation may actually depend on
      whether or not subjects (explicitly or automatically) adopt a strategy of
      simulating the movements. Subjects silently read short phrases describing a
      situation which either involved a motor scene or not (STIMULUS: motor, non-motor
      phrases) and performed a secondary task: either they were explicitly asked to
      imagine the situation or they performed letter detection preventing them from
      using a simulation strategy (TASK: imagery vs. letter detection). In addition,
      phrases were presented both in 1st and 3rd person singular ( PERSPECTIVE: 1st vs.
      3rd person). This allowed us to investigate the influence of the secondary tasks
      (letter detection versus explicit motor imagery) on the neural activity in M1
      during the processing of motor and non-motor phrases. We found differential left
      M1 activity in the task by stimulus interaction with enhanced M1 activation for
      imagery in the presence of motor phrases (vs. non-motor phrases) compared to
      letter detection of motor vs. non-motor phrases. This M1-activity was not
      differentially modulated by perspective. Therefore, M1 activation previously
      found in experiments of silent reading of action words may have resulted from the
      subjects' strategy to mentally simulate the movements during the processing of
      action words.

PMID- 17499161
TI  - Adaptive decision making and value in the anterior cingulate cortex.
AB  - Choosing an appropriate response in an uncertain and varying world is central to
      adaptive behaviour. The frequent activation of the anterior cingulate cortex
      (ACC) in a diverse range of tasks has lead to intense interest in and debate over
      its role in the guidance and control of performance. Here, we consider how this
      issue can be informed by a series of studies considering the ACC's role in more
      naturalistic situations where there is no single certain correct response and the
      relationships between choices and their consequences vary. A neuroimaging study
      of response switching demonstrates that dorsal ACC is not simply concerned with
      self-generated responses or error monitoring in isolation, but is instead
      involved in evaluating the outcome of choices, positive or negative, that have
      been voluntarily chosen. By contrast, an interconnected part of the orbitofrontal
      cortex is shown to be more active when attending to consequences of actions
      instructed by the experimenter. This dissociation is explained with reference to
      the anatomy of these regions in humans as demonstrated by diffusion weighted
      imaging. Lesions to a corresponding ACC region in monkeys has no effect on
      animals' ability to detect or immediately correct errors when response
      contingencies reverse, but renders them unable to sustain appropriate behaviour
      due to an impairment in the ability to integrate over time their recent history
      of choices and outcomes. Taken together, this implies a prominent role for the
      ACC within a distributed network of regions that determine the dynamic value of
      actions and guide decision making appropriately.

PMID- 17499162
TI  - The role of the pre-supplementary motor area in the control of action.
AB  - Although regions within the medial frontal cortex are known to be active during
      voluntary movements their precise role remains unclear. Here we combine
      functional imaging localisation with psychophysics to demonstrate a strikingly
      selective contralesional impairment in the ability to inhibit ongoing movement
      plans in a patient with a rare lesion involving the right pre-supplementary motor
      area (pre-SMA), but sparing the supplementary motor area (SMA). We find no
      corresponding delay in simple reaction times, and show that the inhibitory
      deficit is sensitive to the presence of competition between responses. The
      findings demonstrate that the pre-SMA plays a critical role in exerting control
      over voluntary actions in situations of response conflict. We discuss these
      findings in the context of a unified framework of pre-SMA function, and explore
      the degree to which extant data on this region can be explained by this function
      alone.

PMID- 17499163
TI  - Integrity of white matter in the corpus callosum correlates with bimanual co
      ordination skills.
AB  - Variation in brain structure may reflect variation in functional properties of
      specific brain systems. Structural variation may therefore reflect variation in
      behavioural performance. Here, we use diffusion-weighted magnetic resonance
      imaging to show that variation in white matter integrity in a specific region in
      the body of the corpus callosum is associated with variation in performance of a
      bimanual co-ordination task. When the callosal region showing this association is
      used as a seed for probabilistic tractography, inter-hemispheric pathways are
      generated to the supplementary motor area and caudal cingulate motor area. This
      provides further evidence for the role of medial wall motor areas in bimanual co
      ordination and supports the idea that variation in brain structure reflects inter
      individual differences in skilled performance.

PMID- 17499164
TI  - Action observation has a positive impact on rehabilitation of motor deficits
      after stroke.
AB  - Evidence exists that the observation of actions activates the same cortical motor
      areas that are involved in the performance of the observed actions. The neural
      substrate for this is the mirror neuron system. We harness this neuronal system
      and its ability to re-enact stored motor representations as a means for
      rehabilitating motor control. We combined observation of daily actions with
      concomitant physical training of the observed actions in a new
      neurorehabilitative program (action observation therapy). Eight stroke patients
      with moderate, chronic motor deficit of the upper limb as a consequence of medial
      artery infarction participated. A significant improvement of motor functions in
      the course of a 4-week treatment, as compared to the stable pre-treatment
      baseline, and compared with a control group have been found. The improvement
      lasted for at least 8 weeks after the end of the intervention. Additionally, the
      effects of action observation therapy on the reorganization of the motor system
      were investigated by functional magnetic resonance imaging (fMRI), using an
      independent sensorimotor task consisting of object manipulation. The direct
      comparison of neural activations between experimental and control groups after
      training with those elicited by the same task before training yielded a
      significant rise in activity in the bilateral ventral premotor cortex, bilateral
      superior temporal gyrus, the supplementary motor area (SMA) and the contralateral
      supramarginal gyrus. Our results provide pieces of evidence that action
      observation has a positive additional impact on recovery of motor functions after
      stroke by reactivation of motor areas, which contain the action
      observation/action execution matching system.

PMID- 17499165
TI  - A fronto-parietal network is mediating improvement of motor function related to
      repetitive peripheral magnetic stimulation: A PET-H2O15 study.
AB  - Repetitive peripheral magnetic stimulation (RPMS) is a focused and painless
      stimulation method, in which muscle contractions are elicited by depolarization
      of the terminal motor branches. Clinical-experimental investigations on different
      disorders of sensorimotor integration in the last decade have shown that RPMS can
      be used for the rehabilitation of motor functions after stroke. It is supposed
      that this therapeutic effect is based on the RPMS-induced proprioceptive inflow
      to the CNS. To analyze the conditioning effects of RPMS on reorganization of the
      motor system on cortical level positron emission tomography (PET) is used.
      Regional cerebral blood flow (rCBF) has been measured using H(2)O(15)-PET in
      eight patients with arm paresis following focal cerebral ischemic infarction
      before and after treatment using RPMS on upper arm flexor muscles. Behavioral
      measures showed a significant improvement of kinematics of finger movements and a
      reduction of spasticity in the affected arm following RPMS treatment. The
      recovery was associated with significant increase of neural activation within the
      superior posterior parietal lobe and the premotor cortex (PM) areas. The increase
      of activation of the parieto-premotor network following RPMS treatment indicates
      a significant conditioning effect of RPMS on the cortical level. These results
      emphasize the positive therapeutic effect of RPMS and describe the physiological
      bases of its function on the central level.

PMID- 17499166
TI  - Zones of bimanual and unimanual preference within human primary sensorimotor
      cortex during object manipulation.
AB  - We asked which brain areas are engaged in the coordination of our hands in
      dexterous object manipulations where they cooperate for achieving a common goal.
      Well-trained right-handers steered a cursor on a screen to hit successively
      displayed targets by applying isometric forces and torques to a rigid tool. In
      two bimanual conditions, the object was held freely in the air and the hands thus
      generated coupled opposing forces. Yet, depending on the mapping rule linking
      hand forces and cursor movements, all subjects selected either the left or the
      right hand as prime actor. In two unimanual conditions, the subjects performed
      the same task with either the left or the right hand operating on a fixed tool.
      Functional magnetic resonance imaging revealed common activation across all four
      conditions in a dorsal fronto-parietal network biased to the left hemisphere and
      in bilateral occipitotemporal cortex. Contrary to the notion that medial wall
      premotor areas are especially active in complex bimanual actions, their
      activation depended on acting hand (left, right) rather than on grip type
      (bimanual, unimanual). We observed effects of grip type only in the primary
      sensorimotor cortex (SMC). In particular, with either hand as prime actor,
      bimanual actions preferentially activated subregions of the SMC contralateral to
      the acting hand. A sizeable subregion with preference for unimanual activity was
      found only in the left SMC in our right-handed subjects. Collectively, these
      results indicate a hemispheric asymmetry for the SMC and that partially different
      neural populations support the control of bimanual versus unimanual object
      manipulations.

PMID- 17499167
TI  - Predicting point-light actions in real-time.
AB  - There is convincing evidence for a mirror system in humans which simulates
      actions of conspecifics. One possible purpose of such a simulation system is to
      support action prediction in real-time. Our goal was to study whether the
      prediction of actions involves a real-time simulation process. We motion-captured
      a number of human actions and rendered them as point-light action sequences.
      Observers perceived brief videos of these actions, followed by an occluder and a
      static test posture. We independently varied the occluder time and the movement
      gap (i.e., the time between the endpoint of the action and the test posture).
      Observers were required to judge whether the test stimulus depicted a
      continuation of the action in the same depth orientation. Prediction performance
      was best when occluder time and movement gap corresponded, i.e., when the test
      posture was a continuation of the sequence that matched the occluder duration
      (Experiments 1, 2 and 4). This pattern of results was destroyed when the
      sequences and test images were flipped around the horizontal axis (Experiment 3).
      Overall, our findings suggest that action prediction involves a simulation
      process that operates in real-time. This process can break down when the actions
      are presented under viewing conditions for which observers have little
      experience.

PMID- 17499168
TI  - Understanding non-biological dynamics with your own premotor system.
AB  - The human premotor cortex (PM) appears to subserve a variety of cognitive and
      motor functions, including the prediction of non-biological dynamics. In the
      present study we directly tested the correspondence of premotor correlates of
      predicting different non-biological dynamics and imagining different actions by
      means of functional magnetic resonance imaging. Prediction tasks on either
      spatial, object or rhythmic dynamics were expected to draw on premotor areas
      involved in motor imagery tasks for arm, hand and mouth movements, respectively.
      Firstly, the results confirmed comparable dorsal-to-ventral distributions of
      property effects (in prediction) and movement effects (in motor imagery) in PM.
      Secondly, even more direct correspondences were observed for mouth movement
      imagery and rhythm prediction in inferior ventral PM and for arm movement imagery
      and spatial prediction in dorsal PM. Hand movement imagery and object prediction
      led to activations in closely adjacent areas in left superior ventral PM.
      Together, the present findings support the notion that to-be-predicted stimulus
      dynamics and motor effectors are coupled in lateral PM according to a pragmatic
      default. Beyond that, the results add further support to the notion that the
      human PM is involved in the prediction of many if not all kinds of dynamics.

PMID- 17499169
TI  - Do simple intransitive finger movements consistently activate frontoparietal
      mirror neuron areas in humans?
AB  - The posterior inferior frontal gyrus (pIFG) and anterior inferior parietal lobule
      (aIPL) form the core regions of the human "mirror neuron system" that matches an
      observed movement onto its internal motor representation. We used event-related
      functional MRI to examine whether simple intransitive finger movements evoke
      "mirror activity" in the pIFG and aIPL. In separate sessions, participants either
      merely observed visuospatial stimuli or responded to them as quickly as possible
      with a spatially compatible finger movement. A picture of a relaxed hand with
      static dots on the tip of the index and little finger was continuously presented
      as high-level baseline. Four types of stimuli were presented in a pseudorandom
      order: a color change of a dot, a moving finger, a moving dot, or a simultaneous
      finger-dot movement. Dot movements were spatially and kinematically matched to
      finger movements. Participants were faster at imitating a finger movement than
      performing the same movement in response to a moving dot or a color change of a
      dot. Though imitative responses were facilitated, fMRI revealed no additional
      "mirror activity" in the pIFG and aIPL during the observation or imitation of
      finger movements as opposed to observing or responding to a moving dot. Mere
      observation of a finger movement alone failed to induce significant activation of
      the pIFG and aIPL. The lack of a signature of "mirror neuron activity" in the
      inferior frontoparietal cortex is presumably due to specific features of the task
      which may have favored stimulus-response mapping based on common spatial coding.
      We propose that the responsiveness of human frontoparietal mirror neuron areas to
      simple intransitive movements critically depends on the experimental context.

PMID- 17499170
TI  - fMRI studies of eye movement control: investigating the interaction of cognitive
      and sensorimotor brain systems.
AB  - Functional neuroimaging studies of eye movement control have been a useful
      approach for investigating the interaction of cognitive and sensorimotor brain
      systems. Building on unit recording studies of behaving nonhuman primates and
      clinical studies of patients with a focal brain lesion, functional neuroimaging
      studies have elucidated a pattern of hierarchical organization through which
      prefrontal and premotor systems interact with sensorimotor systems to support
      context-dependent adaptive behavior. Studies of antisaccades, memory-guided
      saccades, and predictive saccades have helped clarify how cognitive brain systems
      support contextually guided and internally generated action. The use of cognitive
      and sensorimotor eye movement paradigms is being used to develop a better
      understanding of life span changes in neurocognitive systems from childhood to
      late life, and about behavioral and systems-level brain abnormalities in
      neuropsychiatric disorders.

PMID- 17499171
TI  - Optic ataxia is not only 'optic': impaired spatial integration of proprioceptive
      information.
AB  - Optic ataxia is considered to be a specific visuo-manual guidance deficit, which
      combines pointing errors due to the use of the contralesional hand ("hand
      effect") and to the presentation of the visual target in the contralesional field
      ("field effect"). The nature of the hand effect has not been identified. The
      field effect is acknowledged as an impaired spatial integration of visual target
      location. However, spatial integration of proprioceptive information from the arm
      has never been experimentally tested in these patients. Here, we specifically
      investigated the capacity of two patients with unilateral optic ataxia in tasks
      requiring different levels of proprioceptive integration from primary information
      processing to proprioceptivo-motor integration. In a first experiment 
      proprioceptive pointing with the ipsilesional hand toward the index finger of the
      contralesional hand- revealed a large mislocalisation of the ataxic hand
      accounting for the hand effect. In a second experiment -proprioceptive pointing
      with the ataxic arm toward the finger of the ipsilesional hand- revealed reaching
      errors for non-visual targets, i.e. optic ataxia is not specific to 'optic'
      targets. Altogether, the present results call for a redefinition of this
      neurological condition in the framework of parietal functions.

PMID- 17499172
TI  - Functional dissociation of saccade and hand reaching control with bilateral
      lesions of the medial wall of the intraparietal sulcus: implications for optic
      ataxia.
AB  - The posterior parietal cortex (PPC) is essential for the integration of
      visuomotor information during visually guided reaching. Studies in macaque
      monkeys have demonstrated a functional specialisation around the intraparietal
      sulcus (IPS) with a more medial representation of hand movements ("parietal reach
      region") and a more lateral representation of saccadic eye movements (lateral
      intraparietal area, LIP). Here we present evidence for the validity of this
      concept with respect to the human parietal cortex. We recorded isolated and
      combined goal-directed eye-hand movements in normal control subjects and in a
      patient with bilateral parieto-occipital lesions and incomplete Balint's syndrome
      including severe optic ataxia (misreaching to visual targets). Brain lesions in
      the patient were caused by acute posterior leucoencephalopathy in association
      with aortic surgery because of Takayasu's arteritis. MRI scans showed bilateral
      line-shaped hemorrhagic lesions, restricted to the cortex at the medial banks of
      the intraparietal sulcus, but leaving its lateral banks largely intact. In the
      patient visually guided reaching was significantly dysmetric, whereas the metrics
      of visually guided saccades were within normal limits. Dysmetria was more
      pronounced for the right visual field, with a gross hypermetria. Variability of
      the movement improved when a delay of 5 or 10 s was introduced between target
      presentation and movement execution. Lesion data support the concept of a
      functional specialisation around the human IPS: The cortex medial to the IPS
      predominantly controls rapid goal-directed reaching movements, comparable to the
      parietal reach region in monkeys, whereas saccadic eye movements appear to be
      controlled rather by the cortex lateral to the IPS.

PMID- 17499174
TI  - Orientation sensitivity to graspable objects: an fMRI adaptation study.
AB  - It has been proposed that vision-for-perception and vision-for-action are
      subserved by distinct streams of visual processing, the ventral and dorsal
      stream, respectively [Milner, A. D., Goodale, M. A., 1995. The visual brain in
      action. Oxford University Press, Oxford]. Such a distinction has been supported
      by a recent functional magnetic resonance (fMR) adaptation study [Valyear, K. F.,
      Culham, J. C., Sharif, N., Westwood, D., Goodale, M. A., 2006. A double
      dissociation between sensitivity to changes in object identity and object
      orientation in the ventral and dorsal visual streams: A human fMRI study.
      Neuropsychologia 44, 218-228], which demonstrated selectivity to object identity
      but not object orientation within the ventral stream, and selectivity to object
      orientation but not object identity within the dorsal stream. These results were
      interpreted as suggesting that changes to object identity (but not to
      orientation) would alter the representation of the stimulus in the
      perceptual/recognition system, whereas changes in object orientation (but not
      necessarily identity) would alter the coding of the stimulus within a visuomotor
      system concerned with behaviour such as grasping. If orientation sensitivity in
      the dorsal stream does reflect such a potential for action, then this sensitivity
      should be specific to graspable objects. Using an fMR adaptation paradigm, we
      presented participants with an image of either a graspable or non-graspable
      stimulus, followed by the same image in either the original orientation or its
      mirror image. One region within the dorsal stream, the lateral occipito-parietal
      junction (lOPJ), was shown to be sensitive to orientation changes for graspable
      stimuli; this region did not show orientation sensitivity for non-graspable
      stimuli. Thus, it appears that the sensitivity to orientation changes in this
      region is specific to graspable objects, presumably because such changes affect
      the affordances of graspable but not non-graspable objects.

PMID- 17499173
TI  - Beyond grasping: representation of action in human anterior intraparietal sulcus.
AB  - The fronto-parietal network has been implicated in the processing of multisensory
      information for motor control. Recent methodological advances with both fMRI and
      TMS provide the opportunity to dissect the functionality of this extensive
      network in humans and may identify distinct contributions of local neural
      populations within this circuit that are not only related to motor planning, but
      to goal oriented behavior as a whole. Herein, we review and make parallels
      between experiments in monkeys and humans on a broad array of motor as well as
      non-motor tasks in order to characterize the specific contribution of a region in
      the parietal lobe, the anterior intraparietal sulcus (aIPS). The intent of this
      article is to review: (1) the historical perspectives on the parietal lobe,
      particularly the aIPS; (2) extend and update these perspectives based on recent
      empirical data; and (3) discuss the potential implications of the revised
      functionality of the aIPS in relationship to complex goal oriented behavior and
      social interaction. Our contention is that aIPS is a critical node within a
      network involved in the higher order dynamic control of action, including
      representation of intended action goals. These findings may be important not only
      for guiding the design of future experiments investigating related issues but may
      also have valuable utility in other fields, such social neuroscience and
      biomedical engineering.

PMID- 17499175
TI  - Does tool-related fMRI activity within the intraparietal sulcus reflect the plan
      to grasp?
AB  - Neuroimaging investigations reliably describe a left-lateralized network of areas
      as underlying the representations of knowledge about familiar tools. Among the
      critical 'nodes' of the network, an area centered within the left intraparietal
      sulcus (IPS) is thought to be related to the motoric representations associated
      with familiar tools and their usage. This area is in the vicinity of an area
      implicated in the control of object-directed grasping actions: the anterior
      intraparietal area, AIP. The current study aimed to evaluate whether this tool
      related intraparietal activity could be accounted for by the graspable nature of
      tools or whether it was due to additional factors such as the functionality of
      tools. First, we found that during a naming task activation within a discrete
      region of the left anterior intraparietal cortex was higher for tools than for
      graspable objects, but did not differ between graspable and non-graspable
      objects. In addition, the peak activity associated with tool naming was found to
      be largely distinct and consistently posterior to that associated with real
      object grasping. A separate region, anterior to the tool-selective focus and
      possibly overlapping with AIP, demonstrated weak selectivity for both tools and
      graspable objects relative to non-graspable objects. These findings indicate that
      this tool-selective area at the anterior end of the left IPS is both separable
      from the grasp-related intraparietal activity and, consistently, it does not
      simply reflect the processing of grasping affordances. Taken together, these
      results suggest that object graspability alone cannot account for the left
      intraparietal activity driven by the naming of tools. Instead, this activity may
      relate to learned motor representations associated with the skillful use of
      familiar tools.

PMID- 17499177
TI  - MR imaging of infectious processes of the knee.
AB  - Infectious processes about the knee can result from the hematogenous spread of
      infection, spread from a contiguous source, direct implantation of pathogens, and
      prior surgery. Soft tissues, joints, and bones can be infected by bacteria,
      fungi, parasites, or viruses. MR imaging is useful in identifying cellulitis,
      abscess, septic arthritis, and osteomyelitis. The inherent tissue contrast
      provided by MR imaging allows for the delineation of soft-tissue infection and
      osteomyelitis. Therefore, MR imaging is a useful tool in evaluating the extent of
      infection, and in facilitating adequate debridement and drainage. MR imaging is
      particularly useful in the setting of chronic posttraumatic osteomyelitis and in
      prior surgical procedures, such as arthroscopy, anterior cruciate ligament
      reconstruction, and amputation.

PMID- 17499179
TI  - Osseous and myotendinous injuries about the knee.
AB  - Osseous injuries may be articular, extra-articular, or physeal, and may be
      related to direct trauma, avulsion forces, or chronic microtrauma. Muscle and
      tendon injuries about the knee may occur alone or in association with more
      significant osseous and ligament injuries. Radiographs or computed radiography
      images remain an important screening technique for patients who have suspected
      knee injuries. After initial radiographs, MR imaging has become the most common
      modality for detection and complete evaluation of osseous and soft-tissue
      injuries about the knee when those radiographs and other techniques do not
      demonstrate clearly the type and extent of injuries. This article focuses on the
      usefulness of MR imaging in the detection, classification, and management of
      bone, muscle, and tendon injuries of the knee.

PMID- 17499178
TI  - MR imaging of the knee: incidental osseous lesions.
AB  - The knee joint remains the articulation most frequently assessed by MR imaging,
      and osseous tumor and tumor-like lesions are not uncommon incidental imaging
      findings. This article reviews the most commonly encountered incidental lesions,
      emphasizing the characteristic MR imaging features. It is intended not as a
      complete review of the imaging findings associated with these lesions but as a
      summary, highlighting the MR imaging features that are most useful in suggesting
      a specific diagnosis. The authors organize incidental lesions into the following
      broad categories: cartilaginous, fibro-osseous, and degenerative. They do not
      address those lesions that are typically symptomatic and, as a result, likely to
      be directly related to the patients' clinical presentation and subsequent
      imaging.

PMID- 17499180
TI  - MR imaging of cysts, ganglia, and bursae about the knee.
AB  - Cystic lesions around the knee comprise a diverse group of entities, ranging from
      benign cysts to complications of underlying diseases such as infection,
      arthritis, and malignancy. Their diverse causes result in varied prognoses and
      therapeutic options. Although the presentation of cystic masses may be similar,
      their management may differ, thus highlighting the importance of appropriate
      categorization. MR aids in the characterization of lesions by first localizing
      them, and then defining their relationship with adjacent structures and
      identifying any additional abnormalities. For the purpose of this article, the
      authors limit the scope of their discussion to benign cysts, ganglia, and bursae
      about the knee.

PMID- 17499181
TI  - Magnetic resonance imaging of the collateral ligaments and the anatomic quadrants
      of the knee.
AB  - Injuries to the lateral and medial supporting structures of the knee can be
      significantly disabling and somewhat difficult to detect and evaluate clinically.
      An accurate imaging evaluation of these structures requires the use of the
      appropriate MR imaging sequences and the detailed knowledge of the anatomic
      structures that are present in these locations. Normal function is dependent on
      the integrity of the complex functional structures and effective clinical
      treatment, including surgical repair, of these structures is predicated on an
      optimal diagnostic evaluation. A successful diagnostic evaluation can expedite
      treatment and provide the best opportunity for a favorable long-term outcome.

PMID- 17499182
TI  - Advanced MR imaging of the cruciate ligaments.
AB  - The anterior and posterior cruciate ligaments are crucial stabilizers of the
      knee. These ligaments are named by the location of their tibial attachments. Each
      ligament is composed of separate functional bundles that differ in size but are
      equally important in function. MR imaging is accurate and sensitive, making it
      the imaging technique of choice for evaluating these ligaments. Acute and chronic
      injuries involving the cruciate ligaments have typical appearances and associated
      findings. MR imaging interpretation must take into account atypical injuries and
      imaging pitfalls. Knowledge of normal ligament reconstruction techniques allows
      differentiation of the normal postoperative appearance from reconstruction
      failure and complications. Ligament reconstruction techniques, complications, and
      appearances are reviewed in this article.

PMID- 17499183
TI  - MR imaging of synovial disorders of the knee: an update.
AB  - Synovial disorders often affect the knee joint and are a common cause of
      morbidity. Before MR imaging, radiologists were limited in their ability to
      provide information about the presence or absence of synovial disease. With the
      advent of MR imaging, useful information can now be provided to referring
      clinicians, often at a time when the initiation of therapy may mitigate
      significantly the long-term sequelae of synovial disorders. MR imaging, owing to
      its superior soft-tissue contrast, is the imaging modality of choice for
      demonstrating and quantifying pathologic changes of the synovium. MR imaging
      provides invaluable information to the clinician regarding the need to either
      initiate or modify therapy in those patients suffering from diseases of, or
      affecting, the synovium.

PMID- 17499184
TI  - MR imaging of the meniscus: review, current trends, and clinical implications.
AB  - MR imaging is the preferred imaging modality for evaluating the meniscus.
      Overall, when strict criteria are followed, it is accurate in diagnosing meniscal
      tears in patients who have not had prior meniscal surgery. However, an accurate
      interpretation requires a through knowledge of the normal meniscal anatomy,
      common meniscal variants, and common diagnostic pitfalls. In this article, the
      author emphasizes the importance of describing meniscal tears properly and
      discusses treatment options. Diagnosing a recurrent tear is more complicated in
      patients who have had prior partial meniscal resection or repair, and the use of
      MR arthrography in this group of patients is discussed. Recent developments in
      areas such as 3 T and parallel imaging offer promise for accurate meniscal
      evaluation with even shorter scan times.

PMID- 17499185
TI  - Three-tesla MR imaging of the knee.
AB  - Three-tesla MR imaging of the knee allows for fast, accurate high-resolution
      imaging. Three-tesla MR imaging is highly accurate in detection of meniscal
      tears. This detection aids referring physicians, because if a meniscal tear is
      not seen on three-tesla MR imaging, it is highly unlikely to be present. High
      field imaging allows for three-dimensional imaging of the knee. Referring doctors
      have found this "virtual arthroscopy" to be useful in presurgical planning.

PMID- 17499188
TI  - [Medical treatment of type 2 diabetes. Recommendations for good practice].

PMID- 17499189
TI  - [Medical treatment of type 2 diabetes. Recommendations for good practice].

PMID- 17499190
TI  - Immunomodulating activities of acidic sulphated polysaccharides obtained from the
      seaweed Ulva rigida C. Agardh.
AB  - Water-soluble acidic polysaccharides from the cell walls of Ulva rigida are
      mainly composed of disaccharides that contain glucuronic acid and sulphated
      rhamnose. The structure of disaccharides resembles that of glycosaminoglycans
      (GAGs) as they both contain glucuronic acid and sulphated sugars.
      Glycosaminoglycans occur in the extracellular matrix of animal connective tissues
      but can also be produced by leucocytes at inflammatory sites. Certain types of
      GAGs can even activate macrophages and therefore the acidic polysaccharides from
      U. rigida probably modulate macrophage activity. In the present study, we
      evaluated the effects of U. rigida polysaccharides on several RAW264.7 murine
      macrophage activities, including expression of inflammatory cytokines and
      receptors, nitric oxide and prostaglandin E2 (PGE(2)) production, and nitric
      oxide synthase 2 (NOS-2) and cyclooxygenase-2 (COX-2) gene expression. U. rigida
      acidic polysaccharides induced a more than two-fold increase in the expression of
      several chemokines (chemokine (C motif) ligand 1, chemokine (C-X-C motif) ligand
      12, chemokine (C-C motif) ligand 22 and chemokine (C-X-C motif) ligand 14
      (Cxcl14)) and in the expression of IL6 signal transducer and IL12 receptor beta
      1. Incubation of macrophages with U. rigida polysaccharides also induced an
      increase in nitrite production, although this effect decreased considerably after
      desulphation of polysaccharides, suggesting that the sulphate group is important
      for the stimulatory capacity of these molecules. U. rigida polysaccharides also
      stimulated macrophage secretion of PGE(2) and induced an increase in COX-2 and
      NOS-2 expression. The results indicate that U. rigida acid polysaccharide can be
      used as an experimental immunostimulant for analysing inflammatory responses
      related to macrophage functions. In addition, these polysaccharides may also be
      of clinical interest for modifying certain macrophage activities in diseases
      where macrophage function is impaired or needs to be boosted.

PMID- 17499191
TI  - Immunomodulation exhibited by piperinic acid through suppression of
      proinflammatory cytokines.
AB  - Piper longum (PL) has been reported for its varied pharmacological activities
      including bio-enhancer and anti-inflammatory activities in traditional medicine.
      Here the premise of the study was to investigate the immunoregulatory potential
      of PL and piperinic acid, one of its active constituent, in Balb/C mice (in vivo)
      and human PBMCs (in vitro) models. Piperinic acid moderated the proinflammatory
      mediators and cytokines in our experiments. At doses of 10, 20, 40 and 80 mg/kg
      p.o. PL showed a dose dependent decrease of lymphocytes (CD4+ and CD8+ T cells)
      and cytokine levels in sensitized Balb/C mice with a marked inhibition at 40
      mg/kg. At an in vitro dose of 20 mug/ml of PL and 5 mug/ml of piperinic acid,
      there was a significant inhibition of mitogen induced human PBMC proliferation,
      mRNA transcripts of IL-2 (ConA) and TNFalpha, IL-1beta and iNOS (LPS)
      respectively under stimulated conditions in time dependent (6 h, 12 h and 24 h
      respectively) expression studies. In parallel, induced nitric oxide production
      was also reduced by stimulated macrophages. Our observations rationalize the
      traditional use of PL and also validate the immunoregulatory potential of
      piperinic acid.

PMID- 17499192
TI  - Influence of early neutrophil depletion on MMPs/TIMP-1 balance in bleomycin
      induced lung fibrosis.
AB  - Pulmonary fibrosis is characterized by excessive deposition of extracellular
      matrix in interstitium resulting in respiratory failure associated with
      inflammation showing mainly neutrophil (PMN) recruitment. The turn over of
      extracellular matrix is partially regulated by proteases such as
      metalloproteinases (MMPs) and their inhibitors (TIMPs). We investigated the
      impact of PMN depletion on the MMP/TIMP-1 imbalance and the development of
      fibrosis in mice induced by bleomycin (0.3 mg/mouse). Administration of 200
      microL of rabbit anti-mouse PMN antibody i.p. blunted the neutrophil influx
      detected in BAL and in whole blood one day after bleomycin administration. At
      day(14), hydroxyproline content was increased both in anti-PMN treated and
      control mice, without any difference between groups. At day one, bleomycin
      elicited a raise in pro-MMP-9 level in BAL that was significantly attenuated in
      anti-PMN depleted mice, whereas TIMP-1 and MMP-2 release were similar in both
      groups at day(1) and day(14). Higher RNA levels were observed in PMN-treated mice
      at day(1) for MMP-9 and MMP-2 and at day(14) for MMP-2 only. At day(14),
      bleomycin elicited a raise of TIMP-1 protein and RNA levels regardless of anti
      PMN treatment, whereas MMP-9 returned to basal level. Bleomycin enhanced MMP-8
      level in BAL at day(14) only for the control group. The amount of MMP-8 was more
      important in BAL from anti-PMN treated mice than in control mice at day(1) and
      day(14). PMN-depletion and the associated modifications in pro-MMP-9/TIMP-1
      imbalance in lung during the early inflammatory phase do not alter susceptibility
      to bleomycin-induced pulmonary fibrosis.

PMID- 17499193
TI  - The effects of the BT/TAMUS 2032 cationic peptides on innate immunity and
      susceptibility of young chickens to extraintestinal Salmonella enterica serovar
      Enteritidis infection.
AB  - The BT/TAMUS 2032 (BT) cationic peptides are a group of related cationic peptides
      produced by a Gram-positive bacterium. Cationic amphiphilic peptides have been
      found to stimulate or prime the innate immune responses in mammals. The innate
      immune system of poultry is functionally inefficient during the first week post
      hatch enabling pathogens such as Salmonella enterica serovar Enteritidis (SE) to
      invade and colonize the visceral organs of these immature birds. The objective of
      the present study was to evaluate the effect of BT as an immunostimulator of the
      innate immune response of young chickens. BT, provided as a feed additive at
      three different concentrations (12, 24, or 48 ppm) for 4 days post-hatch,
      significantly increased protection against SE organ invasion in a concentration
      dependent manner. The functional efficiency of heterophils, the avian equivalent
      to mammalian neutrophils, isolated from chickens fed the BT rations at the three
      concentrations was significantly up-regulated when compared to heterophils
      isolated from chickens fed a control starter ration as determined with an array
      of functional assays. Phagocytosis, oxidative burst, and degranulation were all
      significantly increased in a concentration-dependent manner in heterophils
      isolated from chickens fed the BT diets. This is the first report of bacterial
      cationic peptides inducing the up-regulation of the avian innate immune response
      and providing protection against extraintestinal Salmonella infections. The
      significance of these data is that the orally delivered cationic peptides
      stimulate the innate response at a time of immunologic inefficiency and increased
      susceptibility to bacterial infections (first week post-hatch). Because of the
      nonspecific nature of the innate response, we speculate that BT given as a feed
      additive during the first week post-hatch could provide increased protection
      against a variety of bacterial pathogens.

PMID- 17499194
TI  - Evaluation of anti-tumor effects of tumor cell lysate enriched by HSP-70 against
      fibrosarcoma tumor in BALB/c mice.
AB  - The cytosolic members of the heat shock protein 70 (HSP-70) family have been
      shown to elicit protective cell mediated immunity in animal tumor models. The aim
      of this study was to investigate the effect of the HSP-70 enriched lysate of
      heated tumor cells as vaccines in cancer immunotherapy in the mouse model for
      WEHI-164 fibrosarcoma. Three animal bearing tumor groups were investigated: test
      group; vaccinated with enriched HSP-70 tumor lysate, control group I; vaccinated
      with tumor lysate only and control group II; received PBS. The results indicated
      that vaccinated mice in the test group had resulted in a significant reduction in
      tumor size and longer survival. To find the mechanism of these results, we
      measured the splenocytes proliferation, tumor infiltrated lymphocytes and
      cytotoxic activity of the splenocytes. The results indicated a significant
      increase in the proliferation of mouse splenocytes, a significant increase in the
      CD8+ lymphocytes as well as significant increase in the cytotoxic activity of
      splenocytes against the target cells in the test group. In addition, we analyzed
      the shifting of Th1/Th2 in all the groups. The results indicated a significant
      increase in the IFN-gamma production in the test group. These findings provided a
      useful therapeutic model for development of approaches to cancer treatments.

PMID- 17499195
TI  - In vivo treatment with a nonapeptide thymic hormone, facteur thymique serique
      (FTS), ameliorates chronic colitis induced by dextran sulphate sodium in mice.
AB  - Facteur thymique serique (FTS), a thymic hormone with nonapeptide is involved in
      T cell differentiation in intestine. Here we investigated the effect of FTS on
      dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were subcutaneously
      treated with 1 mug/mouse/day of FTS daily. FTS did not affect the course of acute
      colitis induced by DSS as assessed by survival rate, clinical activity of
      diseases, extent of tissue damage of colons. On the other hand, FTS significantly
      ameliorated chronic colitis induced by multiple cycles of DSS as reflected by
      lower lethality, weight loss, clinical scores and histological scores. The levels
      of interferon (IFN)-gamma, interleukin 1(IL-1)-beta, and IL-12p40 in the culture
      supernatants of lamina propria (LP) cells of colon without any stimulation and
      IFN-gamma by T cells in the LP T cells under T cell receptor (TCR) triggering
      were reduced in FTS-treated mice, whereas the levels of IL-10 by LP cells and LPT
      cells were higher in FTS-treated mice. Thus, FTS may serve to suppress
      inflammation in DSS-induced chronic colitis accompanied by increased IL-10
      production.

PMID- 17499196
TI  - Gab2 antisense oligonucleotide blocks rat basophilic leukemic cell functions.
AB  - Adapter molecule Grb2-associated binder-like protein 2 (Gab2) plays a critical
      role in FcepsilonRI-induced mast cell degranulation and activation. The present
      study aimed to investigate the pharmacological effects of an antisense
      oligonucleotide (ASO) targeted at Gab2 on the immune responses of rat basophilic
      leukemic (RBL)-2H3 cells. Gab2 ASOs were rationally designed and transfected into
      RBL-2H3 cells. Gab2 mRNA and protein knockdown was confirmed by real-time RT-PCR
      and immunoblotting, respectively. Effects of Gab2 ASO on FcepsilonRI-induced
      release of histamine and beta-hexosaminidase was measured by EIA and an enzymatic
      assay, respectively; signaling events by immunoblotting; and cytokine mRNA
      expression by RT-PCR. Effects of Gab2 ASO on cell adhesion and migration were
      performed on fibronectin-coated 96-well plate and transwells cell culture
      chambers, respectively. We have characterized a phosphorothioate-modified ASO
      targeted at Gab2 mRNA that was able to knockdown Gab2 mRNA and protein in RBL-2H3
      cells. Gab2 ASO significantly blocked IgE-mediated mast cell release of beta
      hexosaminidase and histamine; phosphorylation of Akt, p38 mitogen-activated
      protein kinase and PKCdelta; and up-regulation of cytokine mRNA levels (e.g. IL
      4, -6, -9 and -13, and TNF-alpha). In addition, Gab2 ASO markedly prevented mast
      cell adhesion to fibronectin-coated plates and restrained random migration of RBL
      2H3 cells in cell culture chambers. Our findings show that Gab2 knockdown in RBL
      2H3 cells by ASO strategy can suppress many aspects of the mast cell functions
      and, therefore, a selective Gab2 ASO may have therapeutic potential for mast cell
      dependent allergic disorders.

PMID- 17499197
TI  - Studies on the cell-immunosuppressive mechanism of Oridonin from Isodon serra.
AB  - Distinct effects of Oridonin and Lasiodonin, which were extracted from Isodon
      serra was compared by the ratio of IC(50) versus EC(50), the therapeutic index.
      After choosing the more effective one, Oridonin, its immunosuppressive effect and
      mechanism were investigated using BALB/c mouse splenic lymphocytes both in vitro
      and in vivo. When murine splenic lymphocytes was incubated with Oridonin, the
      novel extract effectively suppress the overproduction of the cell stimulated by
      Concanavalin A in a dose and time-dependent manner. This inhibitive activity was
      mainly due to interfering DNA replication in G(1) stages and regulating cell
      cycle and minorly due to decreasing the CD4(+)/CD8(+) lymphocytes level,
      according to Flow cytometry analyses (FCAS) results. Xylene-induced mouse
      tumescence model result suggested that Oridonin depressed the murine ear-swelling
      extent and the level of Interleukin-2 in the blood serum of experimental animals.
      The exciting results of enzyme-linked immunosorbent assay (ELISA) indicated that
      Oridonin could inhibit the secretion of Interleukin-2, Interferon-gamma,
      Interleukin-12p40 and Tumor necrosis factor-alpha in murine splenic lymphocytes.
      Moreover, the results of reverse transcriptase-polymerase chain reaction (RT-PCR)
      confirmed that the inhibition was through decreasing the expression level of
      these cytokines mRNA. Consequently, the results of our research showed that
      Oridonin suppressed overproduction of murine splenic lymphocytes through
      interference of DNA replication, regulation of cell cycle and inhibition of
      cytokine secretion both at protein and mRNA level.

PMID- 17499198
TI  - Inhibition of gene expression and production of iNOS and TNF-alpha in LPS
      stimulated microglia by methanol extract of Phellodendri cortex.
AB  - Activation of microglia has been increasingly associated with the pathogenesis of
      several neurodegenerative disorders including Parkinson's and Alzheimer's
      diseases, and the suppression of microglial activation may lead to alleviation of
      the progression of neurodegeneration in these diseases. We sought to investigate
      whether Phellodendri cortex (PC) that has been used for centuries in Chinese
      traditional medicine for the treatment of various inflammatory conditions,
      inhibits production of anti-inflammatory cytokines and nitric oxide (NO) in
      microglia, and further studied the molecular and cellular mechanisms that govern
      these anti-inflammatory effects. The methanol extract of PC (PC extract)
      attenuated LPS-stimulated increase in production of TNF-alpha, IL-1beta, and NO
      in BV2 cells, a mouse microglia cell line, as well as in primary mouse microglia.
      The RNase protection assay and RT-PCR revealed that the PC extracts inhibited
      increases in mRNAs of these cytokines and iNOS in LPS-stimulated BV2 cells. The
      PC extracts significantly decreased release of these cytokines and NO from LPS
      stimulated microglia in a dose-dependent manner. Molecular mechanisms that govern
      attenuation of the levels of mRNAs and proteins of these cytokines and iNOS
      revealed that the PC extract inhibited LPS-stimulated phosphorylation of ERK and
      activation of NF-kappaB. The studies demonstrate that the PC extract effectively
      inhibits microglial production and release of inflammatory cytokines and NO, and
      could be a candidate agent for anti-inflammation in neurodegenerative human brain
      diseases.

PMID- 17499199
TI  - Inhibitory effects of water-soluble low-molecular-weight beta-(1,3-1,6) d-glucan
      purified from Aureobasidium pullulans GM-NH-1A1 strain on food allergic reactions
      in mice.
AB  - There have been a number of reports showing that the crude beta-glucan fraction
      prepared from various kinds of Basidiomycetes mushrooms acts as anti-cancer and
      anti-allergic reagent through stimulation of IFN-gamma production. It has been
      reported, however, that the exposure of the airway to beta-(1,3) d-glucan,
      contained in house dust, indoor moulds and some bacteria, potentiates the airway
      allergic response. It seems likely that the discrepant effects on immune function
      may be related to such factors as differences of the administration route,
      average molecular weight and water solubility. We isolated a new low-molecular
      weight (about 100 kDa) beta-glucan from Aureobasidium pullulans 1A1 strain of
      black yeast, and found that it had low viscosity and was water-soluble. In this
      study, we examined the effects of water-soluble low-molecular-weight beta-(1-->3)
      and 50-80% branched beta-(1-->6) glucan (LMW-beta-Glucan) isolated from A.
      pullulans on the ova-albumin (OVA)-treated allergic reaction in mice. Feeding
      standard laboratory diets containing 0.5 and 1% LMW-beta-Glucan significantly
      inhibited the OVA-specific IgE elevation compared to that in OVA-sensitized mice
      fed standard laboratory diet alone (control). Furthermore, feeding standard
      laboratory diets containing 0.5 and 1% LMW-beta-Glucan inhibited the reduction of
      IL-12 and IFN-gamma production from splenocytes and the reduction of CD8- and IFN
      gamma-positive cell number in the small intestine of the OVA-sensitized mice.
      These findings suggest that anti-food allergic action of LMW-beta-Glucan may be
      due to the inducing IFN-gamma production in the small intestine and splenocytes.

PMID- 17499200
TI  - Effect of a thiol proteinase inhibitor, E-64-d, on susceptibility to infection
      with Staphylococcus aureus in Chediak-Higashi syndrome (beige) mice.
AB  - We previously reported that abnormally down-regulated protein kinase C (PKC)
      activity is responsible for the impaired cellular function of natural killer
      cells and polymorphonuclear cells (PMNs), and the giant granule formation in
      fibroblasts in the beige mouse, an animal model of Chediak-Higashi syndrome.
      Here, we examine the effect of oral or intraperitoneal administration of E-64-d,
      which protects PKC from calpain-mediated proteolysis, on the impaired cellular
      function in PMNs from beige mice. We found that oral administration of E-64-d
      (12.5 mg/kg body weight per day) for three consecutive days, significantly
      improved the abnormally increased concanavalin A (Con A) cap formation and the
      decreased lysosomal enzyme activity in beige PMNs. In addition, E-64-d
      significantly improved the delayed bactericidal activity against Staphylococcus
      aureus. In contrast, E-64-d at the same dose did not affect these cellular
      functions in PMNs from C57BL/6J mice. We confirmed that the abnormal down
      regulation of PKC after Con A stimulation was eliminated in PMNs from E-64-d
      treated beige PMNs. We then examined whether the administration of E-64-d to
      beige mice improved the susceptibility to experimental infection with S. aureus
      (2x10(8)/mouse). Both intraperitoneal and oral administration of E-64-d to beige
      mice resulted in a significant increase in survival, whereas E-64-d at the same
      dose did not alter the survival rate in normal mice. These results suggest that
      the administration of E-64-d may be effective against severe bacterial infection
      in Chediak-Higashi syndrome.

PMID- 17499201
TI  - A proline-rich polypeptide complex (PRP) isolated from ovine colostrum.
      Modulation of H2O2 and cytokine induction in human leukocytes.
AB  - A proline-rich polypeptide complex (PRP) has immunoregulatory properties and also
      shows beneficial effects in Alzheimer's disease (AD). It is known that the
      unregulated activation of microglial cells in AD may result in chronic
      inflammatory response. There is a link between the activation of immune cells on
      the periphery and in the central nervous system (CNS). Therefore, we studied the
      effect of the PRP on human peripheral blood mononuclear cells (PBMCs) stimulated
      by LPS with PHA (LP) or PMA as proinflammatory activators. PRP and its
      nonapeptide fragment (NP) inhibited by 40-60% production of H(2)O(2) induced by
      PMA. The peptides also inhibited activity of superoxide dismutase. Both peptide
      preparations showed differential effects on the secretion of cytokines. NP
      induced TNF-alpha only while PRP induced IL-6, IL-10 and TNF-alpha. On the other
      hand, the release of TNF-alpha and IL-10 induced by LP in PBMCs was inhibited by
      PRP while NP inhibited the release of IFN-gamma and IL-10. The results obtained
      showed that PRP may affect not only adaptive immunity but also innate immunity
      and thus may regulate secretions of mediators of inflammation. The regulatory
      effect of the PRP on the innate immunity may shed some light on understanding the
      beneficial effects of this polypeptide complex in AD patients.

PMID- 17499202
TI  - Antibody responses in hyperthyroid rats.
AB  - This study evaluated antibody production against sheep red blood cells (SRBC) in
      hyperthyroid rats during treatment with triiodothyronine (T(3)). The immune
      response was evaluated by measuring plaque forming cells (PFC) in the spleen and
      by enzyme-linked immunosorbent assay (ELISA) in serum of male Wistar rats (180+/
      10 g) treated with 25 mug/day of triiodotironine (T(3)) during 7-12 days and
      immunized with SRBC at the 8th day of treatment. The results showed that anti
      SRBC antibody production was significantly decreased in animals treated for 12
      days when compared to normal rats immunized with the same antigen, as evaluated
      by the two assays. These results show that in this experimental model
      hyperthyroidism decreases antibody response. We previously observed the opposite
      effect, that is, an increase in this response in hypothyroid rats resulting from
      the treatment with propylthyouracil, a blocker of thyroid hormone biosynthesis.
      It is suggested that antibody production is affected by thyroid hormone levels.

PMID- 17499203
TI  - Inhibition of IgE-mediated phosphorylation of FcepsilonRIgamma protein by
      antiallergic drugs in rat basophilic leukemia (RBL-2H3) cells: a novel action of
      antiallergic drugs.
AB  - We examined the effect of antiallergic drugs, azelastine and epinastine, on the
      expression of FcepsilonRIalpha, beta, and gamma chains and phosphorylation of the
      gamma chains in rat basophilic leukemia (RBL-2H3) cells. The cells were cultured
      for 24 h with IgE treatment in the presence of azelastine or epinastine at the
      concentration of 10(-5) M. The FcepsilonRIalpha mRNA expression was determined by
      northern blot analysis. The protein level of FcepsilonRI expressed on the plasma
      membrane was examined following IgE treatment by immunoprecipitation with anti
      IgE light chain, followed by western blot analysis with anti-gamma chain of FcR.
      Azelastine and epinastine had no effect on the FcepsilonRIalpha, beta and gamma
      mRNA levels. Although the amount of gamma chain assembled into IgE-bound
      FcepsilonRI was not changed by treatment with azelastine nor epinastine,
      phosphorylation levels of gamma chains of IgE-bound FcepsilonRI were inhibited by
      azelastine. The inhibitory effect of azelastine on the IgE-mediated expression of
      FcepsilonRIgamma protein is not due to their inhibition of mRNA and protein
      expression, but due to abrogating phosphorylation of the gamma chains, which is
      important for initiation of FcepsilonRI signaling cascade elicited by IgE
      interaction.

PMID- 17499204
TI  - Visual processing and the bodily self.
AB  - The 'body schema' has traditionally been defined as a passively updated,
      proprioceptive representation of the body. However, recent work has suggested
      that body representations are more complex and flexible than previously thought.
      They may integrate current perceptual information from all sensory modalities,
      and can be extended to incorporate indirect representations of the body and
      functional portions of tools. In the present study, we investigate the source of
      a facilitatory effect of viewing the body on speeded visual discrimination
      reaction times. Participants responded to identical visual stimuli that varied
      only in their context: being presented on the participant's own body, on the
      experimenter's body, or in a neutral context. The stimuli were filmed and viewed
      in real-time on a projector screen. Careful controls for attention, biological
      saliency, and attribution confirmed that the facilitatory effect depends
      critically on participants attributing the context to a real body. An
      intermediate effect was observed when the stimuli were presented on another
      person's body, suggesting that the effect of viewing one's own body might
      represent a conjunction of an interpersonal body effect and an egocentric effect.

PMID- 17499205
TI  - Interaction forces between colloidal particles in liquid: theory and experiment.
AB  - The interaction forces acting between colloidal particles in suspensions play an
      important part in determining the properties of a variety of materials, the
      behaviour of a range of industrial and environmental processes. Below we briefly
      review the theories of the colloidal forces between particles and surfaces
      including London-van der Waals forces, electrical double layer forces, solvation
      forces, hydrophobic forces and steric forces. In the framework of Derjaguin
      Landau-Verwey-Overbeek (DLVO) theory, theoretical predictions of total
      interparticle interaction forces are discussed. A survey of direct measurements
      of the interaction forces between colloidal particles as a function of the
      surface separation is presented. Most of the measurements have been carried out
      mainly using the atomic force microscopy (AFM) as well as the surface force
      apparatus (SFA) in the liquid phase. With the highly sophisticated and versatile
      techniques that are employed by far, the existing interaction theories between
      surfaces have been validated and advanced. In addition, the direct force
      measurements by AFM have also been useful in the explaining or understanding of
      more complex phenomena and in engineering the products and processes occurring in
      many industrial applications.

PMID- 17499206
TI  - Porous orbital implants, wraps, and PEG placement in the pediatric population
      after enucleation.
AB  - PURPOSE: To investigate complications of various porous orbital implants and
      wrapping materials in the pediatric population after enucleation. DESIGN: A
      retrospective, comparative, nonrandomized study. METHODS: Between November 1992
      and November 2006, patients younger than 15 years old were collected for study
      participation. They underwent enucleation with porous orbital implants primarily
      or secondarily at National Taiwan University Hospital. The authors used the
      hydroxyapatite (HA), Medpor, and Bioceramic orbital implant. The HA implant was
      wrapped with four different materials: donor sclera, Lyodura, porcine sclera, and
      Vicryl mesh. A part of HA implants and all bioceramic implants were wrapped with
      Vicryl mesh, added anteriorly with scleral patch grafts. All Medpor implants were
      unwrapped. RESULTS: Forty-seven cases had more than a two-year follow-up. The
      exposure rates according to implants and wraps were: donor sclera-wrapped HA (two
      of nine, 22%), porcine sclera-wrapped HA (three of three, 100%), Vicryl mesh
      wrapped HA (one of five, 20%), and unwrapped Medpor (one of four, 25%). No
      exposure was found in four Lyodura-wrapped HA implants, and 22 Vicryl mesh
      wrapped HA and Bioceramic implants with anteriorly scleral coating. The exposure
      rate was lower in cases with implants wrapped by our method and Lyodura than in
      those with implants wrapped by other materials (P < .001). Of 47 patients, 20
      (42.5%) were fitted with peg-coupled prostheses and all had good prosthetic
      movements subjectively. CONCLUSIONS: Different types of implants and wraps
      resulted in various exposure rates in the pediatric population. The modified
      wrapping technique may prevent porous implants from exposure in children.

PMID- 17499209
TI  - Continuous chlorophyll degradation accompanied by chlorophyllide and phytol
      reutilization for chlorophyll synthesis in Synechocystis sp. PCC 6803.
AB  - Chlorophyll synthesis and degradation were analyzed in the cyanobacterium
      Synechocystis sp. PCC 6803 by incubating cells in the presence of 13C-labeled
      glucose or 15N-containing salts. Upon mass spectral analysis of chlorophyll
      isolated from cells grown in the presence of 13C-glucose for different time
      periods, four chlorophyll pools were detected that differed markedly in the
      amount of 13C incorporated into the porphyrin (Por) and phytol (Phy) moieties of
      the molecule. These four pools represent (i) unlabeled chlorophyll (12Por12Phy),
      (ii) 13C-labeled chlorophyll (13Por13Phy), and (iii, iv) chlorophyll, in which
      either the porphyrin or the phytol moiety was 13C-labeled, whereas the other
      constituent of the molecule remained unlabeled (13Por12Phy and 12Por13Phy). The
      kinetics of 12Por12Phy disappearance, presumably due to chlorophyll de
      esterification, and of 13Por12Phy, 12Por13Phy, and 13Por13Phy accumulation due to
      chlorophyll synthesis provided evidence for continuous chlorophyll turnover in
      Synechocystis cells. The loss of 12Por12Phy was three-fold faster in a
      photosystem I-less strain than in a photosystem II-less strain and was
      accelerated in wild-type cells upon exposure to strong light. These data suggest
      that most chlorophyll appears to be de-esterified in Synechocystis upon
      dissociation and repair of damaged photosystem II. A substantial part of
      chlorophyllide and phytol released upon the de-esterification of chlorophyll can
      be recycled for the biosynthesis of new chlorophyll molecules contributing to the
      formation of 13Por12Phy and 12Por13Phy chlorophyll pools. The phytol kinase,
      Slr1652, plays a significant but not absolutely critical role in this recycling
      process.

PMID- 17499207
TI  - Clinical features associated with an Asp380His Myocilin mutation in a US family
      with primary open-angle glaucoma.
AB  - PURPOSE: To determine the glaucoma phenotype of an American pedigree with the
      myocilin Asp380His. DESIGN: An observational case series study. METHODS: An
      observational case series study was used to examine a family in which an
      Asp380His myocilin mutation was segregating. Thirteen family members were
      examined and medical records were obtained on the remaining two individuals.
      Blood samples were collected from all 15 participants following the tenets of the
      Helsinki declaration under the auspices of the Oregon Health & Sciences
      University Institutional Review Board and screened for myocilin variants by
      denaturing high-performance liquid chromatography (dHPLC). Any DNA samples with
      dHPLC data different from the control sample were sequenced for base pair
      analysis. RESULTS: An Asp380His myocilin mutation was identified in eight
      members, seven of whom had primary open-angle glaucoma (POAG). The eighth
      individual had high intraocular pressures (IOPs). The disease presents in this
      family with extremely high IOPs requiring trabeculectomies to control the
      pressure. The age at diagnosis ranged from 30 to 45. CONCLUSIONS: This family
      with an Asp380His myocilin mutation presents with an intermediate phenotype
      between juvenile- and adult-onset glaucoma. The Asp380 amino acid residue appears
      to be important in myocilin function based on the finding that substitution of
      this amino acid with four different amino acids (His, Ala, Asn, or Gly) all
      result in a similar presentation of POAG that is intermediate between the more
      severe clinical presentations observed in individuals with the Pro370Leu or
      Lys423Glu variant and the milder findings in patients with the Gln368Stop
      mutation.

PMID- 17499210
TI  - Dimethylsulfoxide-quenched hydrogen/deuterium exchange method to study amyloid
      fibril structure.
AB  - A general method to analyze the structure of a supramolecular complex of amyloid
      fibrils at amino acid residue resolution has been developed. This method combines
      the NMR-detected hydrogen/deuterium (H/D) exchange technique to detect hydrogen
      bonded amide groups and the ability of the aprotic organic solvent
      dimethylsulfoxide (DMSO) to dissolve amyloid fibrils into NMR-observable,
      monomeric components while suppressing the undesired H/D exchange reaction.
      Moreover, this method can be generally applied to amyloid fibrils to elucidate
      the distribution of hydrogen-bonded amino acid residues in the three-dimensional
      molecular organization in the amyloid fibrils. In this study, we describe
      theoretical considerations in the H/D exchange method to obtain the structural
      information of proteins, and the DMSO-quenched H/D exchange method to study a
      supramolecular complex of amyloid fibrils. A possible application of this method
      to study the interaction of a protein/peptide with phospholipid membrane is also
      discussed.

PMID- 17499211
TI  - Otx2 is a putative candidate to activate mice Msx1 gene from distal enhancer.
AB  - A comparative analysis between sequences of Msx1 promoter gene from human, mouse,
      and fugu allowed us to identify sequences highly conserved among these animals.
      One of the regions of great homology is localized between the positions -4622 and
      -4572, including the region described as distal enhancer. In this region putative
      transcription factors binding sites for Nkx2.5, CTF-CBP, Bicoid, Brn2, and Oct
      were found. To evaluate the functionality of these sites we performed EMSA
      analysis using two different regions from the distal enhancer and nuclear protein
      extracts from embryos. The results showed that in the presence of a Bicoid
      consensus binding site a DNA-protein complex can be formed. The identification of
      the proteins involved in this complex by mass spectrometry and Western blotting
      identified OTX2, a Bicoid-like protein. This protein was shown to be present in
      nuclear extracts of the embryonic stages analyzed by Western blot. Altogether
      these results suggest that OTX2 is a putative candidate to activate mice Msx1
      gene from distal enhancer.

PMID- 17499212
TI  - Epitope mapping of mAbs AT8 and Tau5 directed against hyperphosphorylated regions
      of the human tau protein.
AB  - Post-mortem diagnosis of Alzheimer's disease relies on high numbers of senile
      plaques and neurofibrillary tangles (NFTs) stained in distinct brain areas. NFTs
      mostly consist of hyperphosphorylated versions of the microtubule attached tau
      protein (PHF-tau) with more than 30 serine and threonine phosphorylation sites
      identified so far. Characterization of hyperphosphorylated tau regions and the
      hope to develop robust assays for early AD diagnosis relies mostly on
      phosphorylation-dependent monoclonal antibodies (mAbs) recognizing only disease
      specific phosphorylation patterns. Here, we report that anti-PHF-tau mAb AT8
      recognizes an epitope doubly phosphorylated at serine 202 and threonine 205,
      which was not influenced by a third phosphate group at serine 199. But mAb AT8
      was cross-reactive to two doubly phosphorylated motifs containing either serines
      199 and 202 or serines 205 and 208 of the human tau sequence. The epitope of anti
      tau mAb Tau5 was mapped to the human tau sequence 218-225, which is not
      phosphorylated in vivo.

PMID- 17499213
TI  - Ochratoxin A displaces claudins from detergent resistant membrane microdomains.
AB  - Ochratoxin A (OchA) is a food-borne mycotoxin with multiple effects in vivo.
      Previously, we have demonstrated that the toxin can significantly impair the
      barrier function of the gut epithelial cell line, Caco-2. Barrier disruption
      involved loss of claudins 3 and 4, but not claudin 1 from the tight junction
      complex. In this study, we demonstrate for the first time, that OchA is able to
      remove claudins 3 and 4 from the detergent insoluble membrane microdomains
      associated with the tight junctions. However, cholesterol distribution within the
      microdomain was unaffected by the toxin. In addition, the thiol antioxidant, N
      acetyl cysteine, preserved the microdomain localisation of claudins and also the
      barrier function of Caco-2 cells. This work suggests that OchA-mediated barrier
      toxicity is due to removal of claudins from detergent insoluble membrane
      microdomains. Moreover, loss of microdomain association may be due to oxidative
      events.

PMID- 17499214
TI  - BimL involvement in Bax activation during UV irradiation-induced apoptosis.
AB  - Bax, a proapoptotic member of the Bcl-2 family, localizes largely in the
      cytoplasm but translocates to mitochondria and undergoes oligomerization to
      induce the release of apoptogenic factors in response to apoptotic stimuli.
      However, the molecular mechanism of Bax activation is not fully understood. We
      show here the role of BimL in Bax activation during UV irradiation-induced
      apoptosis. In this study, GFP-BimL plasmid was constructed. The dynamic
      interaction between BimL and Bax during UV irradiation-induced apoptosis was
      observed using fluorescence resonance energy transfer (FRET) technique. Our
      experimental results showed that BimL translocation to mitochondria occurred
      before Bax translocation, and that BimL activated Bax indirectly. Moreover,
      inhibition of c-Jun N-terminal protein kinase (JNK) activation blocked BimL
      translocation, delayed and attenuated Bax translocation and subsequent apoptosis.
      These results demonstrate that BimL is involved in UV irradiation-induced
      apoptosis by indirectly activating Bax.

PMID- 17499215
TI  - Wp specific methylation of highly proliferated LCLs.
AB  - The epigenetic regulation of viral genes may be important for the life cycle of
      EBV. We determined the methylation status of three viral promoters (Wp, Cp, Qp)
      from EBV B-lymphoblastoid cell lines (LCLs) by pyrosequencing. Our pyrosequencing
      data showed that the CpG region of Wp was methylated, but the others were not.
      Interestingly, Wp methylation was increased with proliferation of LCLs. Wp
      methylation was as high as 74.9% in late-passage LCLs, but 25.6% in early-passage
      LCLs. From two Burkitt's lymphoma cell lines, Wp specific hypermethylation was
      also found (>80%). Interestingly, the expression of EBNA2 gene which located
      directly next to Wp was associated with its methylation. Our data suggested that
      Wp specific methylation may be important for the indicator of the proliferation
      status of LCLs, and the epigenetic viral gene regulation of EBNA2 gene by Wp
      should be further defined possibly with other biological processes.

PMID- 17499216
TI  - A new homolog of FocA transporters identified in cadmium-resistant Euglena
      gracilis.
AB  - To better understand the cellular mechanism of stress resistance to various
      pollutants (cadmium, pentachlorophenol), we undertook a survey of the Euglena
      gracilis transcriptome by mRNA differential display and cDNA cloning. We
      performed a real-time RT-PCR analysis upon four selected genes. One of them
      significantly changed its expression level in response to stress treatments: B25
      gene was overexpressed in Cd-resistant cells whereas it was down-regulated in PCP
      adapted cells. By Race assays we obtained for B25 a 1093bp cDNA. The deduced
      protein was identified as a bacterial formate/nitrite transporter (FocA) homolog
      and the gene was named EgFth. From all the data, we concluded that EgFth
      overexpression was related to chronic exposure to cadmium.

PMID- 17499217
TI  - Baculovirus surface-displayed hemagglutinin of H5N1 influenza virus sustains its
      authentic cleavage, hemagglutination activity, and antigenicity.
AB  - Baculovirus-mediated transductions of viral glycoprotein genes into mice were
      shown to elicit protective immune response in several reports. Here we reported
      that, under the control of ie1 promoter from white spot syndrome virus,
      hemagglutinin (HA) gene of H5N1 influenza virus could be efficiently expressed in
      both insect and mammalian cells mediated by recombinant baculovirus vectors. The
      HA protein, partially cleaved as in H5N1 virus, was significantly displayed on
      the surface of baculovirus and conferred the viral particle hemagglutination
      activity. Intramuscular injection of the purified HA-displaying baculovirus into
      mice stimulated the production of antibodies with Hemagglutination inhibition and
      neutralization activities against tested influenza virus. These data suggested an
      alternative way to apply baculovirus as an immunizing reagent against influenza
      virus infection.

PMID- 17499218
TI  - Fumonisin B1 exposure and its selective effect on porcine jejunal segment:
      sphingolipids, glycolipids and trans-epithelial passage disturbance.
AB  - Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium verticillioides, the
      cause of Fusarium kernel rot in maize. FB(1) is toxic in domestic and laboratory
      animals, including pigs. This study investigated the effects of a seven-days
      exposure of 1.5mg/kg b.w. FB(1) on the porcine intestinal epithelium.
      Statistically significant increases in the ratio of sphinganine to sphingosine,
      as well as alterations of the glycolipid distribution were observed in the
      jejunum. Using a porcine intestinal epithelial cell line (IPEC-1) derived from
      jejunum and ileum, we tested the effect of FB(1)in vitro in a time- and dose
      dependent fashion. A significant increase in sphinganine concentration was
      observed after 2 days of FB(1) exposure at concentrations >100 microM, or from 6
      days of FB(1) exposure at concentration >20 microM. We were also able to show
      that FB(1) exposure at 200 microM during 16 days increased the intestinal trans
      epithelial flux of FB(1). These data indicate that, in pigs, this mycotoxin acts
      selectively on jejunum cells as follows: (i) FB(1) affects sphingolipid
      metabolism, as demonstrated by an increase of the amount of free sphingoid bases
      in a time- and dose-dependent manner, (ii) a depletion of the glycolipids in
      plasma membranes is observed, and (iii) an increase occurs in the trans
      epithelial flux.

PMID- 17499220
TI  - The anti-inflammatory actions of LCY-2-CHO, a carbazole analogue, in vascular
      smooth muscle cells.
AB  - LCY-2-CHO has anti-inflammatory actions on macrophages. To understand its
      therapeutic implication in atherosclerosis, we examined its effects on the
      expressions of anti-inflammatory and inflammatory proteins in cultured rat aortic
      vascular smooth muscle cells (VSMC). LCY-2-CHO is able to induce heme oxygenase-1
      (HO-1) protein expression through a transcriptional action. The HO-1 inducting
      effect of LCY-2-CHO was inhibited by SB203580, N(G)-nitro-l-arginine methylester
      (l-NAME), and wortmannin, but was not affected by U0126 or SP600125. In
      accordance LCY-2-CHO increased protein phosphorylation of p38, Akt, and eNOS.
      Nrf2 is a transcription factor essential for HO-1 gene induction and we showed
      that LCY-2-CHO is able to cause Nrf2 nuclear translocation and this action
      depends on p38, Akt and eNOS. In addition to induce anti-inflammatory HO-1, LCY-2
      CHO reduced interleukin-1beta (IL-1beta)-induced inflammatory mediators,
      inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), growth-related
      oncogene protein-alpha (GRO-alpha), and interleukin-8 (IL-8). Inhibitory effect
      on IL-1beta-mediated NF-kappaB activation was evidenced by the diminishment of
      IkappaB kinase (IKK) phosphorylation and IkappaBalpha degradation. In contrast,
      IL-1beta-mediated ERK and JNK activations were not changed by LCY-2-CHO, while
      p38 activation by IL-1beta and LCY-2-CHO displayed the non-additivity. Taken
      together, given the overall anti-inflammatory properties of LCY-2-CHO in VSMC, in
      terms to induce HO-1 gene expression and inhibit inflammatory gene expression,
      these results highlight the therapeutic potential of LCY-2-CHO in
      atherosclerosis.

PMID- 17499219
TI  - Depolarization and decreased surface expression of K+ channels contribute to
      NSAID-inhibition of intestinal restitution.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) contribute to gastrointestinal
      ulcer formation by inhibiting epithelial cell migration and mucosal restitution;
      however, the drug-affected signaling pathways are poorly defined. We investigated
      whether NSAID inhibition of intestinal epithelial migration is associated with
      depletion of intracellular polyamines, depolarization of membrane potential
      (E(m)) and altered surface expression of K(+) channels. Epithelial cell migration
      in response to the wounding of confluent IEC-6 and IEC-Cdx2 monolayers was
      reduced by indomethacin (100 microM), phenylbutazone (100 microM) and NS-398 (100
      microM) but not by SC-560 (1 microM). NSAID-inhibition of intestinal cell
      migration was not associated with depletion of intracellular polyamines.
      Treatment of IEC-6 and IEC-Cdx2 cells with indomethacin, phenylbutazone and NS
      398 induced significant depolarization of E(m), whereas treatment with SC-560 had
      no effect on E(m). The E(m) of IEC-Cdx2 cells was: -38.5+/-1.8 mV under control
      conditions; -35.9+/-1.6 mV after treatment with SC-560; -18.8+/-1.2 mV after
      treatment with indomethacin; and -23.7+/-1.4 mV after treatment with NS-398.
      Whereas SC-560 had no significant effects on the total cellular expression of
      K(v)1.4 channel protein, indomethacin and NS-398 decreased not only the total
      cellular expression of K(v)1.4, but also the cell surface expression of both
      K(v)1.4 and K(v)1.6 channel subunits in IEC-Cdx2. Both K(v)1.4 and K(v)1.6
      channel proteins were immunoprecipitated by K(v)1.4 antibody from IEC-Cdx2
      lysates, indicating that these subunits co-assemble to form heteromeric K(v)
      channels. These results suggest that NSAID inhibition of epithelial cell
      migration is independent of polyamine-depletion, and is associated with
      depolarization of E(m) and decreased surface expression of heteromeric K(v)1
      channels.

PMID- 17499221
TI  - Signaling patterns of globus pallidus internal segment neurons during forearm
      rotation.
AB  - We recorded extracellular single unit discharges of globus pallidus internal
      segment (GPi) neurons in monkeys performing a visually driven forearm rotation
      movement task in order to quantify how discharge patterns changed in relation to
      kinematic parameters. Subjects grasped a handle that rotated about its axis while
      facing a video screen displaying visual targets. Continuous visual feedback of
      handle rotation position was provided. Monkeys generated forearm rotation
      movements of +/-35 degrees and +/-70 degrees amplitude in order to align the
      cursor and targets. Trial records were aligned to forearm rotation onset in order
      to compare the discharge patterns that were associated with movements of
      different amplitudes, velocities, and directions. In addition, we quantified the
      depth of modulation of neuronal discharge associated with movements generated in
      two different task phases. Comparisons of discharge patterns were made between
      the visually guided, rewarded phase ("cued movements") and the self-paced,
      unrewarded phase that returned the monkey to the task start position ("return
      movements") by quantifying the goodness of fit between neuronal discharge during
      cued and return movements. Our analyses revealed no systematic relationship
      between the depth of modulation of GPi neurons and forearm rotation amplitude,
      direction, or velocity. Furthermore, comparisons between the two behavioral
      contexts revealed a systematic attenuation of modulation that could not be
      attributed to differences in movement velocity. Collectively, these findings
      suggest that the GPi neurons that we studied were not significantly involved in
      mediating movement kinematics, but may have instead been instrumental in the
      processing of information about the behavioral context during which movements
      were generated.

PMID- 17499222
TI  - Nitric oxide increases in the rat retina after continuous illumination.
AB  - Continuous illumination (CI) of the retina induces an oxidative stress followed
      by the degeneration of photoreceptors. This phenomenon may be partially related
      to the excessive production of nitric oxide (NO). In order to confirm this
      hypothesis, the aims of this work are to determine NO levels during the
      illumination of the retina by electron paramagnetic resonance (EPR), and if an
      increase of NO is found, to characterize the NOS isoform responsible of the
      increment by using Western blot. Sprague-Dawley rats were continuously
      illuminated with white light (12,000 lux) for 2, 24, 48 h, 5 and 7 days while
      control rats were maintained at light/dark cycles of 12/12 h. Using EPR, an
      increase of NO signal was observed in the light exposed retinas peaking at 24 h
      of CI. Western blot analysis showed the expression of iNOS in the illuminated
      retinas with a peak after 24 h of CI, but did not show significant differences of
      nNOS among illuminated and control retinas. In summary, there is an increase of
      NO during CI. Further studies will reveal whether this mechanism is responsible
      for light induced photoreceptor degeneration.

PMID- 17499223
TI  - Synchronizing timelines: relations between fixation durations and N400 amplitudes
      during sentence reading.
AB  - We examined relations between eye movements (single-fixation durations) and RSVP
      based event-related potentials (ERPs; N400s) recorded during reading the same
      sentences in two independent experiments. Longer fixation durations correlated
      with larger N400 amplitudes. Word frequency and predictability of the fixated
      word as well as the predictability of the upcoming word accounted for this
      covariance in a path-analytic model. Moreover, larger N400 amplitudes entailed
      longer fixation durations on the next word, a relation accounted for by word
      frequency. This pattern offers a neurophysiological correlate for the lag-word
      frequency effect on fixation durations: word processing is reliably expressed not
      only in fixation durations on currently fixated words, but also in those on
      subsequently fixated words.

PMID- 17499224
TI  - Adenosine ecto-deaminase (ecto-ADA) from porcine cerebral cortex synaptic
      membrane.
AB  - We have purified and investigated the role of adenosine ecto-deaminase (ecto-ADA)
      in porcine brain synaptic membranes and found a low activity of ecto-ADA in
      synaptic preparations from the cerebral cortex, hippocampus, striatum and medulla
      oblongata in the presence of purine transport inhibitors (NBTI, dipyridamole and
      papaverine). The purification procedure with affinity chromatography on epoxy
      Toyopearl gel/purine riboside column as a crucial step of purification allowed a
      214-fold purification of synaptic ecto-ADA with a yield of 30%. Gel filtration
      chromatography revealed a molecular mass estimated at 42.4+/-3.9 kDa. The enzyme
      had a broad optimum pH and was not affected by mono- and divalent cations. Ecto
      ADA revealed a low affinity to adenosine (Ado) and 2'-deoxyadenosine (2'-dAdo)
      (K(M)=286.30+/-40.38 microM and 287.14+/-46.50 microM, respectively). We compared
      the affinity of ecto-ADA to the substrates with the physiological and
      pathological concentrations of the extracellular Ado in brains that do not exceed
      a low micromolar range even during ischemia and hypoxia, and with the affinity of
      adenosine receptors to Ado not exceeding a low nanomolar (A(1) and A(2A)
      receptors) or low micromolar (A(2B) and A(3)) range. Taken together, our data
      suggest that the role of synaptic ecto-ADA in the regulation of the ecto-Ado
      level in the brain and in the termination of adenosine receptor signaling is
      questionable. The porcine brain synapses must have other mechanisms for the ecto
      Ado removal from the synaptic cleft and synaptic ecto-ADA may also play an extra
      enzymatic role in cell adhesion and non-enzymatic regulation of adenosine
      receptor activity.

PMID- 17499225
TI  - Transcriptional regulation of polysialylated neural cell adhesion molecule
      expression by NMDA receptor activation in retinoic acid-differentiated SH-SY5Y
      neuroblastoma cultures.
AB  - NMDA receptors exhibit a dichotomy of signaling with excessive stimulation
      leading to neuronal damage that occurs during neurodegenerative disorders,
      whereas the normal burst of activity results in plastic responses with the
      expression of molecular substrates of long-term plasticity, growth and survival.
      Control of polysialylated neural cell adhesion molecule (PSA-NCAM) expression by
      NMDA receptor activation has been described in several systems, suggesting a
      functional link between these two proteins. The coordinated induction of several
      different transcription factors initiated by NMDA receptor stimulation may be a
      key mechanism in the orchestration of specific target gene expression that
      underlies various aspects of CNS function, including plastic responses. We report
      here the transcriptional regulation of PSA-NCAM expression by subtoxic dose of
      NMDA in retinoic acid-differentiated SH-SY5Y cell cultures. SH-SY5Y cell cultures
      differentiated with retinoic acid (10 microM) were exposed to NMDA (100 microM)
      or to antagonist MK-801 (200 nM) prior to treatment with NMDA and cells were
      harvested after 24 h of treatment to study the expression of PSA-NCAM, nuclear
      factor kappaB (NF-kappaB) and activator protein-1 (AP-1) by Western blotting and
      dual immunocytofluorescence and expression of polysialyltransferase (PST) mRNA by
      fluorescent in situ hybridization (FISH). We observed the induction of
      transcription factors NF-kappaB and AP-1 along with PSA-NCAM expression in
      response to NMDA receptor activation. Also, PSA-NCAM regulation in response to
      NMDA receptor activity was shown to be transcriptionally controlled, as seen by
      temporal and spatial changes observed in the expression of PST mRNA in NMDA
      treated SH-SY5Y cell cultures. This raises the interesting possibility that NF
      kappaB and AP-1 expression is involved in propagating the signals of NMDA
      receptor activity that leads to downstream strengthening of long-term plasticity
      changes in differentiated SH-SY5Y neuroblastoma cell cultures. Thus understanding
      the regulation of PSA-NCAM expression by NMDA receptor-mediated activity may
      represent a fundamental prerequisite for the development of therapies in order to
      maintain neuronal plasticity throughout life and functional recovery after brain
      damage.

PMID- 17499226
TI  - Effect of BDNF depletion on the formation of Ruffini endings in vibrissa
      follicles and the survival of their mechanoreceptive neurons in trigeminal
      ganglion.
AB  - We examined the influence of BDNF depletion in peripheral tissues on the
      formation of Ruffini endings and their neuronal survival by injections of
      neutralizable anti-BDNF antibody into mouse mystacial pads for periods of 5 days
      at different developmental stages of the Ruffini endings (the pre-formation stage
      from the 2nd to 6th day after birth, the formation stage from the 4th to 8th, or
      the post-formation stage from the 10th to 14th). The treatment at the pre
      formation and formation stages caused a significant decrease in the number of
      Ruffini endings in vibrissa follicles. This decrease in Ruffini endings was
      accompanied with a significant increase in neuron apoptosis in the trigeminal
      ganglion (TG) in both stages. However, at the post-formation stage, the anti-BDNF
      injection showed no effect on the formation of the mechanoreceptors nor their
      neuronal survival. In the post-formation stage, the axoplasmic spins of Ruffini
      endings were circumferentially embraced with the cytoplasmic processes of
      terminal Schwann cells. The present study indicates that target-derived BDNF is
      essential for survival of mechanoreceptive nerves in the pre-formation and
      formation stages, but not in the post-formation stages of their development. It
      seems that Schwann cells participate in this switch-over of neuronal dependency
      on brain-derived neurotrophic factor.

PMID- 17499227
TI  - Angiotensin II-mediated oxidative stress and inflammation mediate the age
      dependent cardiomyopathy in ACE2 null mice.
AB  - OBJECTIVES: The peptidase action of angiotensin converting enzyme 2 (ACE2) allows
      it to function as a negative regulator of the renin-angiotensin system. Current
      pharmacotherapies for human heart failure, such as ACE inhibitors and angiotensin
      and aldosterone receptor blockers, increase the activity of ACE2 in the heart. In
      this study, we investigate the mechanism for the age-dependent cardiomyopathy in
      ACE2 null mice. METHODS AND RESULTS: Ace2(-/y) mutant mice develop a progressive
      age-dependent dilated cardiomyopathy with increased oxidative stress,
      neutrophilic infiltration, inflammatory cytokine and collagenase levels, mitogen
      activated protein kinase (MAPK) activation and pathological hypertrophy. The
      angiotensin II receptor-1 (AT1) blocker, irbesartan, prevented the dilated
      cardiomyopathy in aged Ace2(-/y) mutant mice, confirming a critical role of
      angiotensin II (Ang II)-mediated stimulation of AT1 receptors. Ang II activation
      of AT1 receptors triggers G-protein-coupled receptor (GPCR)-activated
      phosphoinositide 3-kinase gamma (PI3Kgamma) and its downstream pathways. We
      showed that p110gamma, the catalytic subunit of PI3Kgamma, is a key mediator of
      NADPH oxidase activation in response to Ang II. The double mutant mice (Ace2(
      /y)/p110gamma(-/-)) exhibited marked reductions in oxidative stress, neutrophilic
      infiltration, and pathological hypertrophy resulting in myocardial protection,
      suggesting that PI3Kgamma plays a critical role in Ang II-mediated
      cardiomyopathy. CONCLUSIONS: Our findings demonstrate that the age-dependent
      cardiomyopathy in ACE2 null mice is related to increased Ang II-mediated
      oxidative stress and neutrophilic infiltration via AT1 receptors. Our combination
      of genetic and pharmacological approaches defines a critical role of ACE2 in the
      suppression of Ang II-mediated heart failure.

PMID- 17499228
TI  - The RhoA/Rho kinase pathway in the myocardium.

PMID- 17499229
TI  - Overexpression of histidine-rich Ca-binding protein protects against
      ischemia/reperfusion-induced cardiac injury.
AB  - OBJECTIVE: The histidine-rich Ca-binding protein (HRC) is a Ca-storage protein in
      cardiac sarcoplasmic reticulum. Recent transgenic studies revealed that this
      protein inhibits the maximal rates of sarcoplasmic reticulum Ca-transport,
      leading to cardiac dysfunction. In view of the role of sarcoplasmic reticulum Ca
      cycling in myocardial ischemia/reperfusion injury, we designed this study to gain
      further insight into the role of HRC during ischemia/reperfusion. METHODS AND
      RESULTS: The transgenic mouse model with cardiac-specific overexpression of HRC
      was utilized and cardiac contractile parameters were assessed before and after
      ischemia/reperfusion injury by Langendorff perfusion. After a 20-min
      stabilization period, the hearts were subjected to 40 min of global ischemia,
      followed by 60 min of reperfusion. We found that although transgenic (TG) hearts
      showed depressed cardiac function (25%) compared to wild types (WTs) at baseline,
      they exhibited better recovery of left ventricular developed pressure (86.6+/
      2.6% in TGs vs. 58.3+/-4.0% in WTs of pre-ischemic values, P<0.05) and higher
      rates of contraction and relaxation after ischemia/reperfusion than WTs. This
      improvement was accompanied by smaller infarcts (23.1+/-1.7% in TGs vs. 41.1+/
      2.5% in WTs of infarct region-to-risk region ratio, P<0.05) and lower creatine
      kinase release. Notably, the extent of apoptotic cell death was significantly
      attenuated, as evidenced by decreased DNA fragmentation, upregulation of the
      antiapoptotic protein Bcl-2, and downregulation of the active caspases (3, 9 and
      12) following ischemia/reperfusion in TG hearts, compared with WTs. Extension of
      these studies to an in vivo model of 30-min myocardial ischemia, via coronary
      artery occlusion, followed by 24-h reperfusion, showed that the infarct region-to
      risk region ratio was 9+/-0.9% in TGs, compared with 20.4+/-2.9% in WTs (P<0.05).
      CONCLUSIONS: Our findings suggest that increased cardiac HRC expression protects
      against ischemia/reperfusion injury in the heart, resulting in improved recovery
      of function and reduced infarction.

PMID- 17499231
TI  - Molecular interaction between caveolin-1 and ABCA1 on high-density lipoprotein
      mediated cholesterol efflux in aortic endothelial cells.
AB  - OBJECTIVE: Caveolin-1 and ATP-binding cassette transporter A1 (ABCA1) are
      proteins that are involved in cellular cholesterol efflux. In this study, we
      analyzed the relationships between caveolin-1 and ABCA1 on high-density
      lipoprotein (HDL)-mediated cholesterol efflux in rat aortic endothelial cells.
      METHODS AND RESULTS: Overexpression of caveolin-1 by transfection with caveolin-1
      cDNA in aortic endothelial cells up-regulated ABCA1 expression and enhanced
      cholesterol efflux. Suppression of caveolin-1 by siRNA decreased ABCA1 expression
      and reduced cholesterol efflux. The number of caveolae increased after
      transfection with caveolin-1 into cells. Immunoprecipitation assays revealed a
      molecular interaction between caveolin-1 and ABCA1 in the plasma membrane and in
      the cytoplasm after HDL incubation. Immunoelectron microscopy demonstrated that
      caveolin-1 colocalized with ABCA1 in the caveolae and in the cytoplasmic
      vesicles; it was also found that caveolin-1 and ABCA1 colocalized with cellular
      cholesterol by immunofluorescence microscopy. Blocking of intracellular lipid
      transport by inhibitors disrupted the interaction between caveolin-1 and ABCA1
      and reduced cholesterol to methyl-beta-cyclodextrin and HDL. CONCLUSIONS: The
      molecular interaction between caveolin-1 and ABCA1 is associated with the HDL
      mediated cholesterol efflux pathway in aortic endothelial cells.

PMID- 17499230
TI  - NADPH oxidase-derived superoxide anion mediates angiotensin II-enhanced carotid
      body chemoreceptor sensitivity in heart failure rabbits.
AB  - OBJECTIVE: A previous study from this laboratory showed that elevation of
      endogenous angiotensin II (Ang II) and upregulation of the angiotensin II type 1
      (AT(1)) receptor in the carotid body (CB) are involved in the enhanced peripheral
      chemoreceptor sensitivity in rabbits with chronic heart failure (CHF). NADPH
      oxidase-derived superoxide anion mediates the effects of Ang II in many organs.
      We investigated whether this signaling pathway may mediate the enhanced
      peripheral chemoreceptor sensitivity induced by Ang II in CHF rabbits. METHODS
      AND RESULTS: By recording single-unit activity from the carotid sinus nerve in
      isolated preparations, we found that phenylarsine oxide 2 muM (PAO, NADPH oxidase
      inhibitor) and TEMPOL 1 mM (superoxide dismutase mimetic) significantly decreased
      not only the Ang II-enhanced CB chemoreceptor responses to different levels of
      hypoxia in sham rabbits (Delta-12.5+/-0.8 and Delta-12.8+/-0.9 imp/s at 40.7+/
      2.3 mm Hg of PO(2), and Delta-5.6+/-0.5 and Delta-5.3+/-0.4 imp/s at 60.2+/-3.1
      mm Hg of PO(2), p<0.05, respectively) but also the CHF-induced elevation of CB
      chemoreceptor responses to different levels of hypoxia (Delta-13.6+/-1.1 and
      Delta-13.7+/-0.9 imp/s at 40.9+/-3.1 mm Hg of PO(2), and Delta-6.7+/-1.2 and
      Delta-6.6+/-0.8 imp/s at 59.8+/-3.5 mm Hg of PO(2), p<0.05). In addition, mRNA
      and protein expressions of NADPH oxidase components (gp91(phox), p40(phox) and
      p47(phox)) were higher in the CB from CHF rabbits compared to sham rabbits.
      Furthermore, 100 pM Ang II induced an increase in superoxide production in CB
      homogenates from sham rabbits, which was similar to that in CB homogenate from
      CHF rabbits. PAO and Tempol inhibited the Ang II- and CHF-enhanced superoxide
      anion production. CONCLUSIONS: These results suggest that the enhanced peripheral
      chemoreceptor sensitivity mediated by Ang II in CHF rabbits occurs via a NADPH
      oxidase-superoxide signaling pathway.

PMID- 17499232
TI  - Globular and full-length forms of adiponectin mediate specific changes in glucose
      and fatty acid uptake and metabolism in cardiomyocytes.
AB  - OBJECTIVE: Our aim was to investigate the regulation of glucose and fatty acid
      metabolism in cardiomyocytes by the globular (gAd) and full-length (fAd) forms of
      adiponectin. METHODS: We produced fAd (consisting of high, medium and low
      molecular weight oligomers) in a mammalian expression system and gAd in bacteria.
      These were used to treat primary neonatal rat cardiomyocytes (up to 48 h), and we
      employed 3H- or 14C-labeled substrates to monitor glucose uptake and subsequent
      metabolism via oxidation, glycogen synthesis or lactate production and fatty acid
      uptake and oxidation. Enzymatic assay for acetyl CoA carboxylase activity was
      employed, and protein phosphorylation and expression was determined by
      immunoblotting cell lysates. The role of adiponectin receptor (AdipoR) isoforms
      was determined via siRNA-mediated knockdown. RESULTS: There was an initial (1 h)
      increase in glucose uptake and oxidation in response to gAd or fAd. Fatty acid
      uptake was stimulated by gAd or fAd, and by 24 h a decrease in acetyl CoA
      carboxylase activity and elevated fatty acid oxidation were observed. After 48 h
      increased fatty acid oxidation correlated with decreased glucose oxidation and
      pyruvate dehydrogenase activity, while glycogen synthesis and lactate production
      increased. Both gAd and fAd elicited phosphorylation of AMP kinase, insulin
      receptor substrate-1, Akt and glycogen synthase kinase-3beta. Knockdown of
      AdipoR1 or AdipoR2 attenuated the effect of both gAd and fAd on fatty acid uptake
      and oxidation. Only AdipoR1 knockdown prevented the ability of gAd (1 h) to
      increase glucose uptake and oxidation; however, reducing either AdipoR1 or
      AdipoR2 expression attenuated the long-term (24 h) effects of gAd. CONCLUSIONS:
      These results clearly demonstrate that gAd and fAd mediate distinct and time
      dependent effects on cardiomyocyte energy metabolism via AdipoR1 and AdipoR2.

PMID- 17499233
TI  - Association of serum levels of glycated albumin, C-reactive protein and tumor
      necrosis factor-alpha with the severity of coronary artery disease and renal
      impairment in patients with type 2 diabetes mellitus.
AB  - OBJECTIVES: This study aimed to determine whether elevated serum levels of
      glycated albumin, high-sensitivity C-reactive protein (hsCRP) and tumor necrosis
      factor (TNF)-alpha were related to an increased risk for coronary artery disease
      (CAD) and renal insufficiency in patients with type 2 diabetes mellitus (T2DM).
      DESIGN AND METHODS: Serum levels of glycated albumin, hsCRP, TNF-alpha and blood
      glycosylated hemoglobin A1c (HbA1c) were measured in 317 consecutive patients
      with T2DM and 309 normal controls. Patients with T2DM were grouped based upon
      coronary angiographic findings (Group I: 151 patients with normal coronary
      arteries; Group II: 166 patients with significant coronary stenosis [>70% luminal
      diameter narrowing]) and renal functional status evaluated by estimated
      creatinine clearance (CrCl) (normal renal function group: 187 patients with CrCl
      >90 mL/min; mild renal insufficiency group: 103 patients with CrCl 60-90 mL/min;
      moderate renal insufficiency group: 27 patients with CrCl 30-60 mL/min).
      Multivariate analysis was performed to determine independent risk factors for CAD
      and renal insufficiency in patients with T2DM. RESULTS: Serum levels of glycated
      albumin, hsCRP and TNF-alpha were significantly higher in Group II than in
      controls (P<0.01) and Group I (P<0.01). A significant difference was found in
      glycated albumin, hsCRP and TNF-alpha levels among diabetic patients with mild,
      moderate renal insufficiency and normal renal function (P<0.05). These
      biochemical measurements correlated significantly with number of diseased
      coronary vessels (P<0.01) and status of renal function (P<0.05). No difference
      existed in HbA1c levels between Group II and Group I, and among patients with
      various CrCL stages. Multivariate analysis revealed that male gender, old age and
      serum levels of glycated albumin, hsCRP, TNF-alpha and lipoprotein (a) were
      independent risk factors for CAD, and older age, hypertension and glycated
      albumin were for CrCl <60 mL/min in diabetes. CONCLUSIONS: Increased serum levels
      of glycated albumin, hsCRP and TNF-alpha are associated with the presence and
      severity of CAD and renal impairment in patients with T2DM.

PMID- 17499234
TI  - A comprehensive study on the major mutations in glucose-6-phosphate dehydrogenase
      deficient polymorphic variants identified in the coastal provinces of Caspian Sea
      in the north of Iran.
AB  - BACKGROUND: The aim of this study was the molecular analysis of G6PD patients for
      G6PD mutations in the coastal provinces of the Caspian Sea in north of Iran.
      METHODS: Studies on G6PD deficiency in the coastal provinces of the Caspian Sea
      in Iran were performed in 248 patients with a history of favism, in Mazandaran,
      Golestan and Gillan provinces, which contributed 74, 71 and 103 samples,
      respectively. Three different major polymorphic variants were determined by
      molecular analysis, using SSCP, sequencing and PCR-RFLP methods. Firstly, all
      Mazandaranian samples were searched for the Mediterranean mutation by PCR-RFLP
      method. The remaining samples of the Mazandaran province were analysed by SSCP
      followed by sequencing for other mutations. Then, our research was expanded in
      two other provinces, Golestan and Gillan, by the PCR-RFLP method. RESULTS: Three
      different major polymorphic variants were found: G6PD Mediterranean 75.4% (187
      out of 248), G6PD Chatham 19.76% (49 out of 248), G6PD Cosenza 2.02% (5 out of
      248) and 7 samples out of 248 remained unknown. Also, there was no significant
      difference in the incidence of various G6PD polymorphic variants with mean age,
      and various blood work values such as Hb, WBC and MCV between two major variants
      (p>0.20). CONCLUSIONS: These results which are the first molecular investigation
      in north of Iran indicate a higher prevalence of G6PD Chatham in this large
      Iranian population than anywhere else in the world. The distribution of these
      G6PD variants is more similar to that found in an Italian population (80-84% for
      Mediterranean, 20% for Chatham and 1.9% for Cosenza mutation). Although the
      origin of Iranian population is rather uncertain, the closer similarity of the
      mutation spectrum to Italian rather than Middle Eastern population may indicate
      that these populations have a common ancestral origin.

PMID- 17499235
TI  - Hypotensive effect of profilin on rabbit intraocular pressure.
AB  - Ocular hypertension is a negative process that occurs within the eye and is the
      main risk factor to develop glaucoma, a progressive loss of vision due to
      degeneration of retinal ganglion cells. The protein transduction technique allows
      a cargo to cross biological membranes. Using this technique we have previously
      shown that a membrane permeable version of profilin I (PTD4-profilin) increased
      aqueous humour outflow facility. Here we have investigated if a topical
      application of PTD4-profilin was able to modify intraocular pressure in rabbits.
      10 microM PTD4-profilin (10 microL), reduced intraocular pressure by 20% compared
      to the control vehicle, this value being in the range of other commercial drugs,
      which produced intraocular pressure reductions between 18 and 35%. The mean-time
      effect for PTD4-profilin was 6.8 h and was also in the same range as commercial
      products that provided values between 4.3 and 5.5 h. According to the results
      presented here we propose PTD4-profilin as a new approach for the treatment of
      ocular hypertension and PTD4 as a new strategy to facilitate the penetration of
      molecules into the eye.

PMID- 17499236
TI  - Role of cannabinoid CB2 receptors in glucose homeostasis in rats.
AB  - Here we show that the activation of cannabinoid CB2 receptors improved glucose
      tolerance after a glucose load. Blockade of cannabinoid CB2 receptors
      counteracted this effect, leading to glucose intolerance. Since blockade of
      cannabinoid CB1 receptors mimics the actions of cannabinoid CB2 receptor
      agonists, we propose that the endocannabinoid system modulates glucose
      homeostasis through the coordinated actions of cannabinoid CB1 and CB2 receptors.
      We also describe the presence of both cannabinoid CB1 and CB2 receptor
      immunoreactivity in rat pancreatic beta- and non-beta-cells, adding the endocrine
      pancreas to adipose tissue and the liver as potential sites for endocannabinoid
      regulation of glucose homeostasis.

PMID- 17499237
TI  - Resveratrol inhibits proliferation of cultured rat cardiac fibroblasts:
      correlated with NO-cGMP signaling pathway.
AB  - Rhizoma polygoni cuspidate, used as a traditional Chinese herb, offered the
      therapeutic potential for cardiovascular diseases. Resveratrol, extracted from
      root of the rhizoma polygoni cuspidate has sparked increasing interest in
      therapeutic application. Resveratrol was shown to exert a variety of
      pharmacological effects including cardioprotective and cancer chemopreventive
      properties. However, its mechanisms of the action are not completely understood.
      The aim of this study was to investigate the molecular mechanism of resveratrol
      on preventing cardiac fibroblasts from proliferative and hypertrophic response
      induced by angiotensin II. Cell proliferation and cytotoxicity were detected by
      methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) release assay,
      respectively. Hypertrophic response of cardiac fibroblasts was measured by mRNA
      expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide
      (BNP). Resveratrol (25, 50, 75, and 100 microM) inhibited cardiac fibroblasts
      proliferation in a dose- and time-dependent manner compared with angiotensin II
      group (P<0.01), and the inhibitory effects were blocked by pretreatment with N(G)
      nitro-l-arginine methyl ester (L-NAME) and 1H-[1,2,4]-oxadiazole-[4,3-a]
      quinoxalin-1-one (ODQ). Resveratrol increased nitric oxide (NO) and nitric oxide
      synthase (NOS) levels in culture medium, increased intracellular cyclic GMP
      (cGMP) level in cardiac fibroblasts, and decreased ANP and BNP levels in culture
      medium. The mRNA expression of ANP and BNP was suppressed by resveratrol. These
      results suggested that resveratrol inhibited cardiac fibroblasts proliferation
      induced by angiotensin II, and the inhibitory effect might be associated with the
      activation of NO-cGMP signaling pathway.

PMID- 17499238
TI  - Effects of BAY 41-2272, an activator of nitric oxide-independent site of soluble
      guanylate cyclase, on human NADPH oxidase system from THP-1 cells.
AB  - We investigated the effects of the 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H
      pyrazolo[3,4-b] pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) on the NADPH
      oxidase activity, gp91(phox) gene expression, cyclic guanosine-3',5'
      monophosphate (cGMP) and cyclic adenosine-3',5'-monophosphate (cAMP) levels in
      the human myelomonocytic THP-1 cell line. THP-1 cells treated with BAY 41-2272
      (0.3-10 microM) for 48 h significantly increased the superoxide anion (O(2)(*-))
      release. This increase was not affected when cells were pre-treated with the
      specific cGMP-phosphodiesterase inhibitor zaprinast, the soluble guanylate
      cyclase inhibitor 1H-[1,2,4] oxidiazolo[4,3-alpha] quinoxalin-1-one (ODQ), the
      adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl) adenine (SQ 22,536) or the
      nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME).
      In addition, BAY 41-2272 (3 and 10 microM; 48 h) was able to increase gp91(phox)
      gene expression on THP-1 cells. The pre-treatment with zaprinast, 3-isobutyl-l
      methyl-xanthine (IBMX; 0.5 mM), ODQ, SQ 22,536 or l-NAME caused no additional
      effect on the expression of gp91(phox) evoked by BAY 41-2272. Treatment of THP-1
      cells with BAY 41-2272 caused a significant increase in cGMP and cAMP levels. Our
      findings show that BAY 41-2272 caused a significant increase on the O(2)(*-)
      release and gp91(phox) gene expression by THP-1 cells, and an elevation of
      intracellular cGMP and cAMP levels. However, we could not detect a clear
      correlation between both O(2)(*-) release and gp91(phox) gene expression with
      activation of cGMP and cAMP signaling pathways.

PMID- 17499239
TI  - Interleukin-1beta suppresses epithelial sodium channel beta-subunit expression
      and ENaC-dependent fluid absorption in human middle ear epithelial cells.
AB  - Recent reports have shown that cytokines inhibit fluid absorption by suppressing
      Na(+) channel activity in various epithelia. In this study, we investigated the
      role of epithelial sodium channel (ENaC) in fluid absorption in normal human
      middle ear epithelial (NHMEE) cells, as well as the effects of Interleukin (IL)
      1beta on ENaC expression and fluid absorption in NHMEE cells. We confirmed that
      ENaC alpha, beta and gamma were predominantly expressed on the apical surface of
      the NHMEE cells by immunocytochemistry. Addition of amiloride, a potent ENaC
      blocker, to apical membranes of NHMEE cells decreased the fluid absorption rate
      in a dose-dependent manner. Treatment with 10 ng/ml IL-1beta for 24 h suppressed
      ENaC beta expression, the ENaC-dependent short-circuit current (Isc), and ENaC
      dependent fluid absorption. When the NHMEE cells were pretreated with a
      phospholipase C (PLC)inhibitor (U73122, 10 microM), a protein kinase C (PKC)
      inhibitor (Calphostin C, 0.1 microM), or extracellular signal regulated kinase
      (ERK) 1/2 inhibitor (PD98059, 10 microM), the amiloride-sensitive currents in IL
      1beta-treated cells were reversed to control levels; an effect not seen with
      SB202190 (an inhibitor of p38 mitogen-activated protein (MAP) kinase) or SP600125
      (a reversible inhibitor of c-Jun N-terminal kinase). In this study we showed that
      ENaC is essential for fluid absorption in NHMEE cells and that IL-1beta
      suppresses the ENaC-dependent current via the PLC-PKC-ERK1/2 pathway. These
      results suggest that IL-1beta may contribute to fluid retention in otitis media
      with effusion by changing electrolyte transport and reducing middle ear
      epithelial fluid absorption.

PMID- 17499240
TI  - Allosteric effects of R- and S-citalopram on the human 5-HT transporter: evidence
      for distinct high- and low-affinity binding sites.
AB  - The human 5-HT transporter (hSERT) has two binding sites for 5-HT and 5-HT uptake
      inhibitors: the orthosteric high-affinity site and a low-affinity allosteric
      site. Activation of the allosteric site increases the dissociation half-life for
      some uptake inhibitors. The objectives of this study were 1) to identify hSERT
      mutations that inactivate the high-affinity site without affecting the allosteric
      site and 2) to observe allosteric effects in which hSERT binds R-citalopram with
      higher affinity than S-citalopram. Wild-type and mutant (Y95F, I172M, and
      Y95F/I172M) hSERTs were expressed in COS-7 cells, and their 5-HT uptake and
      uptake inhibitor-binding abilities were studied. The hSERT mutations did not
      alter affinities for 5-HT or paroxetine, but high-affinity binding of S
      citalopram was severely affected, particularly by the I172M, and Y95F/I172M
      mutations - K(i) respectively 4 nM (wild-type), 35 nM, 1000 nM, and 17.100 nM
      (mutants). The allosteric site however, in wild-type hSERT and the three mutants
      was unaffected by the mutations as attenuation of the dissociation rate of the
      [(3)H]-paroxetine:hSERT complex in the presence of S-citalopram or paroxetine was
      the same for wild-type hSERT and the three mutants. Further, R-citalopram
      previously thought of as an inactive enantiomer strongly attenuated dissociation
      of the wild-type [(3)H]-imipramine:hSERT complex, whereas S-citalopram had almost
      no effect on this complex. These results suggest that 1: The allosteric site on
      hSERT is distinct from the site to which S-citalopram binds with high affinity.
      2: The allosteric effects of R-citalopram on the dissociation of [(3)H]
      imipramine from hSERT indicate that R-citalopram introduces a conformational
      change in hSERT.

PMID- 17499241
TI  - Mechanism of relaxation induced by nicotine in normal and ovalbumin-sensitized
      guinea-pig trachea.
AB  - Nicotine is an irritant molecule in the cigarette that contributes airway hyper
      reactivity. The aim of this study was to investigate the mechanism of these
      effects and effects of nicotine on the isolated trachea preparations from control
      and ovalbumin-sensitized guinea-pigs. Nicotine (3x10(-5) to 3x10(-4) M) produced
      concentration-dependent relaxation on isolated trachea preparations precontracted
      by carbachol (10(-6) M) in both groups. We found that the relaxant effect of
      nicotine decreased in the presence of N(w)-nitro L-arginine methyl ester (L-NAME)
      (10(-6) M), and hexamethonium (10(-2) M) but not in the presence of alpha
      bungarotoxin (10(-3) M), and tetrodotoxin (3.1x10(-6) M) in isolated trachea
      preparations in both groups. The relaxant effect of nicotine was less significant
      in isolated trachea preparations from ovalbumin-sensitized guinea-pigs than from
      control guinea-pigs (P<0.05). The contractions elicited by carbachol (10(-6) M)
      were not significantly different in the ovalbumin-sensitized group than in the
      control group. Nicotine (10(-4) M) significantly increased the cGMP levels in
      trachea preparations compared with the control preparations.(P<0.05). These
      results suggest that nicotine-induced relaxation response in normal and ovalbumin
      sensitized guinea-pigs trachea is at least in part mediated by nitric oxide (NO)
      since it was significantly reduced in the presence of L-NAME. The decreased
      relaxation response to nicotine in ovalbumin sensitized guinea-pigs trachea may
      be due to impaired production and/or liberation of NO.

PMID- 17499242
TI  - Intra- and extracellular signaling by endothelial neuregulin-1.
AB  - Suppression of tumor growth by inhibition of ErbB receptor signaling is well
      documented. However, relatively little is known about the ErbB signaling system
      in the regulation of angiogenesis, a process necessary for tumor growth. We have
      previously shown that heparin-binding EGF-like growth factor (HB-EGF) is
      expressed by vascular endothelial cells (EC) and promotes endothelial recruitment
      of vascular smooth muscle cells (SMC). To assess whether other members of the EGF
      family regulate angiogenesis, the expression of 10 EGF-like growth factors in
      primary ECs and SMCs was analyzed. In addition to HB-EGF, neuregulin-1 (NRG-1)
      was expressed in ECs in vitro and in vivo. Endothelial NRG-1 was constitutively
      processed to soluble extracellular and intracellular signaling fragments, and its
      expression was induced by hypoxia. NRG-1 was angiogenic in vivo in mouse corneal
      pocket and chicken chorioallantoic membrane (CAM) assays. However, consistent
      with the lack of NRG-1 receptors in several primary EC lines, NRG-1 did not
      directly stimulate cellular responses in cultured ECs. In contrast, NRG-1
      promoted EC responses in vitro and angiogenesis in CAM in vivo by mechanisms
      dependent on VEGF-A and VEGFR-2. These results indicate that NRG-1 is expressed
      by ECs and regulates angiogenesis by mechanisms involving paracrine up-regulation
      of VEGF-A.

PMID- 17499243
TI  - Plakins in development and disease.
AB  - Plakins are large multi-domain molecules that have various functions to link
      cytoskeletal elements together and to connect them to junctional complexes.
      Plakins were first identified in epithelial cells where they were found to
      connect the intermediate filaments to desmosomes and hemidesmosomes [Ruhrberg,
      C., and Watt, F.M. (1997). The plakin family: versatile organizers of
      cytoskeletal architecture. Curr Opin Genet Dev 7, 392-397.]. They were
      subsequently found to be important for the integrity of muscle cells. Most
      recently, they have been found in the nervous system, where their functions
      appear to be more complex, including cross-linking of microtubules (MTs) and
      actin filaments [Leung, C.L., Zheng, M., Prater, S.M., and Liem, R.K. (2001). The
      BPAG1 locus: Alternative splicing produces multiple isoforms with distinct
      cytoskeletal linker domains, including predominant isoforms in neurons and
      muscles. J Cell Biol 154, 691-697., Leung, C.L., Sun, D., Zheng, M., Knowles,
      D.R., and Liem, R.K. (1999). Microtubule actin cross-linking factor (MACF): a
      hybrid of dystonin and dystrophin that can interact with the actin and
      microtubule cytoskeletons. J Cell Biol 147, 1275-1286.]. These plakins have also
      indicated their relationship to the spectrin superfamily of proteins and the
      plakins appear to be evolutionarily related to the spectrins, but have diverged
      to perform different specialized functions. In invertebrates, a single plakin is
      present in both Drosophila melanogaster and Caenorhabditis elegans, which
      resemble the more complex plakins found in mammals [Roper, K., Gregory, S.L., and
      Brown, N.H. (2002). The 'spectraplakins': cytoskeletal giants with
      characteristics of both spectrin and plakin families. J Cell Sci 115, 4215
      4225.]. In contrast, there are seven plakins found in mammals and most of them
      have alternatively spliced forms leading to a very complex group of proteins with
      potential tissue specific functions [Jefferson, J.J., Leung, C.L., and Liem, R.K.
      (2004). Plakins: goliaths that link cell junctions and the cytoskeleton. Nat Rev
      Mol Cell Biol 5, 542-553.]. In this review, we will first describe the plakins,
      desmoplakin, plectin, envoplakin and periplakin and then describe two other
      mammalian plakins, Bullous pemphigoid antigen 1 (BPAG1) and microtubule actin
      cross-linking factor 1 (MACF1), that are expressed in multiple isoforms in
      different tissues. We will also describe the relationship of these two proteins
      to the invertebrate plakins, shortstop (shot) in Drosophila and VAB-10 in C.
      elegans. Finally, we will describe an unusual mammalian plakin, called epiplakin.

PMID- 17499244
TI  - Ethylene induces zygote formation through an enhanced expression of zyg1 in
      Dictyostelium mucoroides.
AB  - We have previously demonstrated that a potent plant hormone, ethylene induces
      sexual development including zygote formation in Dictyostelium cells, and that a
      novel gene (zyg1) is also involved in zygote formation. Based on these findings,
      the present work was mainly designed to reveal (1) the precise relationship
      between the ethylene amount and zygote formation, and (2) the relation of in situ
      ethylene synthesis to zyg1 expression, using transformants that over- or under
      produce ACC-oxidase (Dd-aco) involved in ethylene biosynthesis. ACO(OE) cells
      overexpressing Dd-aco gene overproduced ethylene and exhibited the augmented
      zygote formation. In contrast, ACO-RNAi cells, in which the expression of Dd-aco
      was suppressed by the RNAi method, showed a reduced level of ethylene production,
      thus resulting in inhibition of zygote formation. Importantly, the expression of
      zyg1 was affected by the amount of ethylene produced: Zyg1 expression was
      augmented in ACO(OE) cells, but was significantly suppressed in ACO-RNAi cells.
      In another experiment, we found that 1-methylcyclopropene (1-MCP), which is known
      to inhibit the function of ethylene by binding specifically to ethylene
      receptors, greatly suppresses zygote formation. These results indicate that
      ethylene is capable of inducing zygote formation through the expression of zyg1.

PMID- 17499245
TI  - Rice black-streaked dwarf virus minor core protein P8 is a nuclear dimeric
      protein and represses transcription in tobacco protoplasts.
AB  - Virus-encoding nuclear transcriptional regulators play important roles in the
      viral life cycle. Most of these proteins exhibit intrinsic transcriptional
      activation or repression activity, and are involved in the regulation of the
      expression of virus genome itself or important cellular genes to facilitate viral
      replication and inhibit antiviral responses. Here, we report that the minor core
      protein P8 of Rice black-streaked dwarf virus, a dsRNA virus infecting host
      plants and insects, is targeted to the nucleus of insect and plant cells via its
      N-terminal 1-40 amino acids and possesses potent active transcriptional
      repression activity in Bright Yellow-2 tobacco suspension cells. Moreover, P8,
      like many transcriptional regulatory proteins, is capable of forming homo-dimers
      within insect cells and in vitro. All these data suggest that P8 is likely to
      enter the nucleus of host cell and play an important role as a negative
      transcriptional regulator of host gene expression during the process of virus
      host interaction.

PMID- 17499246
TI  - Glycoprotein folding and the role of EDEM1, EDEM2 and EDEM3 in degradation of
      folding-defective glycoproteins.
AB  - Proteins synthesized in the endoplasmic reticulum (ER) lumen are exposed to
      several dedicated chaperones and folding factors that ensure efficient
      maturation. Nevertheless, protein folding remains error-prone and mutations in
      the polypeptide sequence may significantly reduce folding-efficiency. Folding
      incompetent proteins carrying N-glycans are extracted from futile folding cycles
      in the calnexin chaperone system upon intervention of EDEM1, EDEM2 and EDEM3,
      three ER-stress-induced members of the glycosyl hydrolase 47 family. This review
      describes current knowledge about mechanisms regulating folding and disposal of
      glycoproteins.

PMID- 17499247
TI  - Extracellular heat shock proteins in cell signaling.
AB  - Extracellular stress proteins including heat shock proteins (Hsp) and glucose
      regulated proteins (Grp) are emerging as important mediators of intercellular
      signaling and transport. Release of such proteins from cells is triggered by
      physical trauma and behavioral stress as well as exposure to immunological
      "danger signals". Stress protein release occurs both through physiological
      secretion mechanisms and during cell death by necrosis. After release into the
      extracellular fluid, Hsp or Grp may then bind to the surfaces of adjacent cells
      and initiate signal transduction cascades as well as the transport of cargo
      molecules such as antigenic peptides. In addition Hsp60 and hsp70 are able to
      enter the bloodstream and may possess the ability to act at distant sites in the
      body. Many of the effects of extracellular stress proteins are mediated through
      cell surface receptors. Such receptors include Toll Like Receptors 2 and 4, CD40,
      CD91, CCR5 and members of the scavenger receptor family such as LOX-1 and SREC-1.
      The possession of a wide range of receptors for the Hsp and Grp family permits
      binding to a diverse range of cells and the performance of complex multicellular
      functions particularly in immune cells and neurones.

PMID- 17499248
TI  - Clinical information does not improve the performance of mathematical models in
      predicting the outcome of pregnancies of unknown location.
AB  - OBJECTIVE(S): To see if the incorporation of clinical variables can improve the
      diagnostic performance of logistic regression models in the prediction of
      pregnancy of unknown location (PUL) outcome. DESIGN: Prospective observational
      study. SETTING: Early Pregnancy Unit, St George's Hospital, University of London,
      London. PATIENT(S): All women with a PUL were included in the final analysis.
      This was defined on transvaginal ultrasonography (TVS) as there being no signs of
      either an intra- or an extrauterine pregnancy or retained products of conception
      in a woman with a positive pregnancy test. INTERVENTION(S): Noninterventional
      study; all women classified with a PUL were managed expectantly. MAIN OUTCOMES
      MEASURE(S): Data were collected prospectively from women classified as having a
      PUL. More than 30 clinical, ultrasonographic and biochemical end points were
      defined and recorded for analysis (these included risk factors for ectopic
      pregnancy [EP] and site-specific tenderness on TVS). Women were followed until
      the final diagnosis was established: failing PUL, intrauterine pregnancy (IUP),
      or EP. A multinomial logistic regression model (M5) was developed on 197 training
      cases and tested prospectively on a further 173 PUL cases. The performance of M5
      was evaluated using receiver operating characteristic (ROC) curves and compared
      with logistic regression model M4 (hCG ratio [hCG 48 h/hCG 0 h], logarithm [log]
      of hCG average, and quadratic effect of the hCG ratio {[hCG ratio-1.17] x [hCG
      ratio-1.17]}), which was previously published. RESULT(S): Data from 376
      consecutive women with a PUL were included in the analysis: 201 in the training
      set (109 [55.3%] failing PUL, 76 [38.6%] IUP, and 12 [6.1%] EP; four with a
      persisting PUL were excluded from the analysis) and 175 in the test set (94
      [54.3%] with a failing PUL, 64 [37.0%] with an IUP, and 15 [8.7%] with an ectopic
      pregnancy; two with a persisting PUL were excluded from analysis). The most
      useful independent prognostic variables for the logistic regression model, M5,
      were as follows: log of serum hCG average, amount of vaginal bleeding, hCG ratio,
      and quadratic effect of the hCG ratio. On the test set, this model gave an area
      under the ROC curve of 0.979 for failing PUL, 0.979 for IUP, and 0.912 for EP.
      This model outperformed M4, which gave areas under the ROC curve of 0.978, 0.974,
      and 0.900, respectively; however, this was not significant. CONCLUSION(S):
      Clinical information does not significantly improve the performance of logistic
      regression models in the prediction of PUL outcome. On the basis of our results,
      we believe that historical, examination, and ultrasonographic factors are not
      essential input variables in logistic regression model building in the PUL
      population. When approaching women with a PUL, biochemical data alone, and in
      particular the hCG ratio, can be used to predict PUL outcome with a high degree
      of certainty.

PMID- 17499250
TI  - Short-day increases in aggression are independent of circulating gonadal steroids
      in female Siberian hamsters (Phodopus sungorus).
AB  - Among the suite of adaptations displayed by seasonally-breeding rodents,
      individuals of most species display reproductive regression and concomitant
      decreases in gonadal steroids during the winter. In addition, some species
      display increased aggression in short "winter-like" days compared with long
      "summer-like" day lengths. For example, male Syrian and Siberian hamsters held in
      short days express heightened levels of aggression that are independent of
      gonadal steroids. Virtually nothing is known, however, regarding seasonal
      aggression in female Siberian hamsters (Phodopus sungorus). Studies were
      undertaken to determine female levels of aggression in long and short days as
      well as the role of gonadal steroids in mediating this behavior. In Experiment 1,
      females were housed in long or short days for 10 weeks and resident-intruder
      aggression was assessed. Prior to testing, estrous cycle stages were determined
      by vaginal cytology and females were tested during both Diestrus I and Proestrus.
      In Experiment 2, hormone levels were experimentally manipulated; long-day females
      were ovariectomized (OVx) or given sham surgeries whereas short-day females were
      implanted with capsules containing 17beta-estradiol (E(2)) or Progesterone (P).
      In Experiment 3, both long- and short-day females were ovariectomized and
      implanted with either an exogenous E(2) or blank capsule, or given a sham
      surgery. Short-day hamsters displayed increased aggression relative to long-day
      females. Aggression was not affected by estrous stage. There was no difference in
      aggression between long-day OVx and sham animals. Furthermore, neither exogenous
      E(2) nor P had any significant effect on aggression. These results support
      previous findings of increased non-breeding aggression and suggest that short-day
      aggression is not likely mediated by circulating levels of gonadal steroids.
      These results also suggest that the endocrine regulation of seasonal aggression
      may be similar between the sexes.

PMID- 17499251
TI  - Sexual behavior of male pigs.
AB  - Two major characteristics of males that affect the likelihood of achieving
      copulation are the sexual motivation and mating competency of the male. The
      behavior of domestic animals, including their sexual behavior, is dependent upon
      a complex interaction between the organism's internal and external environment.
      In male pigs, as in other mammalian species, it is clear that testicular steroids
      are required to maintain sexual behavior and testosterone plays a critical role.
      Consistent with studies in other species, it is apparent in male pigs that there
      is a threshold circulating concentration of androgens and/or estrogens required
      to maintain sexual behavior and that the level of sexual motivation is unrelated
      to levels of sex steroids providing these are adequate for normal sexual
      behavior. Key aspects of the external environment that affect the sexual behavior
      of the male pig include genetic, seasonal, social, sexual and psychological
      factors.

PMID- 17499252
TI  - Maternal weight gain and neonatal intensive care unit admissions.

PMID- 17499249
TI  - Sexual behavior in male rodents.
AB  - The hormonal factors and neural circuitry that control copulation are similar
      across rodent species, although there are differences in specific behavior
      patterns. Both estradiol (E) and dihydrotestosterone (DHT) contribute to the
      activation of mating, although E is more important for copulation and DHT for
      genital reflexes. Hormonal activation of the medial preoptic area (MPOA) is most
      effective, although implants in the medial amygdala (MeA) can also stimulate
      mounting in castrates. Chemosensory inputs from the main and accessory olfactory
      systems are the most important stimuli for mating in rodents, especially in
      hamsters, although genitosensory input also contributes. Dopamine agonists
      facilitate sexual behavior, and serotonin (5-HT) is generally inhibitory, though
      certain 5-HT receptor subtypes facilitate erection or ejaculation. Norepinephrine
      agonists and opiates have dose-dependent effects, with low doses facilitating and
      high doses inhibiting behavior.

PMID- 17499253
TI  - Re: Plasma interleukin (IL)-18 concentrations is elevated in patients with
      previous myocardial infarction and related to severity of coronary
      atherosclerosis independently of C-reactive protein and IL-6 [Atherosclerosis 188
      (2006) 450-454].

PMID- 17499254
TI  - A simplified approach to quasi-linear viscoelastic modeling.
AB  - The fitting of quasi-linear viscoelastic (QLV) constitutive models to material
      data often involves somewhat cumbersome numerical convolution. A new approach to
      treating quasi-linearity in 1-D is described and applied to characterize the
      behavior of reconstituted collagen. This approach is based on a new principle for
      including nonlinearity and requires considerably less computation than other
      comparable models for both model calibration and response prediction, especially
      for smoothly applied stretching. Additionally, the approach allows relaxation to
      adapt with the strain history. The modeling approach is demonstrated through
      tests on pure reconstituted collagen. Sequences of "ramp-and-hold" stretching
      tests were applied to rectangular collagen specimens. The relaxation force data
      from the "hold" was used to calibrate a new "adaptive QLV model" and several
      models from literature, and the force data from the "ramp" was used to check the
      accuracy of model predictions. Additionally, the ability of the models to predict
      the force response on a reloading of the specimen was assessed. The "adaptive QLV
      model" based on this new approach predicts collagen behavior comparably to or
      better than existing models, with much less computation.

PMID- 17499255
TI  - The mechanics of mouse skeletal muscle when shortening during relaxation.
AB  - The dynamic properties of relaxing skeletal muscle have not been well
      characterised but are important for understanding muscle function during
      terrestrial locomotion, during which a considerable fraction of muscle work
      output can be produced during relaxation. The purpose of this study was to
      characterise the force-velocity properties of mouse skeletal muscle during
      relaxation. Experiments were performed in vitro (21 degrees C) using bundles of
      fibres from mouse soleus and EDL muscles. Isovelocity shortening was applied to
      muscles during relaxation following short tetanic contractions. Using data from
      different contractions with different shortening velocities, curves relating
      force output to shortening velocity were constructed at intervals during
      relaxation. The velocity component included contributions from shortening of both
      series elastic component (SEC) and contractile component (CC) because force
      output was not constant. Early in relaxation force-velocity relationships were
      linear but became progressively more curved as relaxation progressed. Force
      velocity curves late in relaxation had the same curvature as those for the CC in
      fully activated muscles but V(max) was reduced to approximately 50% of the value
      in fully activated muscles. These results were the same for slow- and fast-twitch
      muscles and for relaxation following maximal tetani and brief, sub-maximal
      tetani. The measured series elastic compliance was used to partition shortening
      velocity between SEC and CC. The curvature of the CC force-velocity relationship
      was constant during relaxation. The SEC accounted for most of the shortening and
      work output during relaxation and its power output during relaxation exceeded the
      maximum CC power output. It is proposed that unloading the CC, without any change
      in its overall length, accelerated cross-bridge detachment when shortening was
      applied during relaxation.

PMID- 17499256
TI  - Quantitative structure-(chromatographic) retention relationships.
AB  - Since the pioneering works of Kaliszan (R. Kaliszan, Quantitative Structure
      Chromatographic Retention Relationships, Wiley, New York, 1987; and R. Kaliszan,
      Structure and Retention in Chromatography. A Chemometric Approach, Harwood
      Academic, Amsterdam, 1997) no comprehensive summary is available in the field.
      Present review covers the period of 1996-August 2006. The sources are grouped
      according to the special properties of kinds of chromatography: Quantitative
      structure-retention relationship in gas chromatography, in planar chromatography,
      in column liquid chromatography, in micellar liquid chromatography, affinity
      chromatography and quantitative structure enantioselective retention
      relationships. General tendencies, misleading practice and conclusions,
      validation of the models, suggestions for future works are summarized for each
      sub-field. Some straightforward applications are emphasized but standard ones.
      The sources and the model compounds, descriptors, predicted retention data,
      modeling methods and indicators of their performance, validation of models, and
      stationary phases are collected in the tables. Some important conclusions are:
      Not all physicochemical descriptors correlate with the retention data strongly;
      the heat of formation is not related to the chromatographic retention. It is not
      appropriate to give the errors of Kovats indices in percentages. The apparently
      low values (1-3%) can disorient the reviewers and readers. Contemporary mean
      interlaboratory reproducibility of Kovats indices are about 5-10 i.u. for
      standard non polar phases and 10-25 i.u. for standard polar phases. The
      predictive performance of QSRR models deteriorates as the polarity of GC
      stationary phase increases. The correlation coefficient alone is not a
      particularly good indicator for the model performance. Residuals are more useful
      than plots of measured and calculated values. There is no need to give the
      retention data in a form of an equation if the numbers of compounds are small.
      The domain of model applicability of models should be given in all cases.

PMID- 17499257
TI  - Sedimentation field flow fractionation to study human erythroleukemia cell
      megakaryocytic differentiation after short period diosgenin induction.
AB  - Anti-cancer differentiation therapy could be one strategy to stop cancer cell
      proliferation. We propose a new sedimentation field flow fractionation (SdFFF)
      cell separation application in the field of cancer research. It concerns the
      study of megakaryocytic differentiation processes after a short exposure to an
      inducting agent (diosgenin). Washout process and early dual SdFFF separation-
      removing the influence of diosgenin and decreasing the influence of
      undifferentiated cells--resulted in the preparation of an enriched population to
      study the mechanism and kinetics of megakaryocytic differentiation. A short
      exposure to diosgenin was able to induce complete differentiation leading to
      maximal maturation which ended naturally after 192h incubation without the
      influence of a secondary effect of diosgenin. The study of isolated
      undifferentiated cells also showed that no resistance to diosgenin was observed.
      This result suggested different sensitivities to differentiation induction, and
      SdFFF cell separation would be of great interest to explore this phenomena.

PMID- 17499258
TI  - Development and validation of a fast method for determination of free glycerol in
      biodiesel by capillary electrophoresis.
AB  - In this study, a capillary electrophoresis (CE) methodology for the determination
      of free glycerol in biodiesel using oxidative cleavage with periodate was
      optimized and validated. The amount of iodate produced in the reaction was
      determined by CE. The optimized electrolyte was 20 mmol L(-1) glycine and 10 mmol
      L(-1) trifluoroacetic acid (direct UV detection, 210 nm). The short total
      analysis time (less than 28 s) was obtained using the short end injection mode.
      The optimization of the method was carried out using Peakmaster software. The
      choice of the components of the run electrolyte and of the internal standard
      (nitrate) was made through the use of effective mobility curves. A good
      correlation coefficient higher than 0.9991 and low LOD 4.3 mg L(-1) was obtained.
      The recovery of free glycerol was 95.4-102.4%. This method was used to determine
      glycerol in commercial biodiesel samples.

PMID- 17499259
TI  - Semi-automated disk-type solid-phase extraction method for polychlorinated
      dibenzo-p-dioxins and dibenzofurans in aqueous samples and its application to
      natural water.
AB  - A disk-type solid-phase extraction (SPE) method was used for the extraction of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in natural water
      and tap water. Since this SPE system comprised airtight glass covers with a
      decompression pump, it enabled continuous extraction with semi-automation. The
      disk-type SPE method was validated by comparing its recovery rates of spiked
      internal standards with those of the liquid-liquid extraction (LLE). The recovery
      ranges of both methods were similar in terms of (13)C-labeled internal standards:
      64.3-99.2% for the LLE and 52.4-93.6% for the SPE. For the native spike of
      1,3,6,8-tetrachlorinated dibenzo-p-dioxin (TCDD) and octachlorinated dibenzo-p
      dioxin (OCDD), the recoveries in the SPE were in the normal range of 77.9-101.1%.
      However, in the LLE, the recoveries of 1,3,6,8-TCDD decreased significantly. One
      of the reasons for the low recovery is that the solubility of this congener is
      high. The semi-automated SPE method was applied to the analysis of different
      types of water: river water, snow, sea water, raw water for drinking purposes,
      and tap water. PCDD/F congeners were found in some sea water and snow samples,
      while their concentrations in the other samples were below the limits of
      detection (LODs). This SPE system is appropriate for the routine analysis of
      water samples below 50L.

PMID- 17499260
TI  - Quantitative determination of acetyl glucoside isoflavones and their metabolites
      in human urine using combined liquid chromatography-mass spectrometry.
AB  - To investigate whether the bioavailability of isoflavones could be an alternative
      to fermented soy foods, the conjugated forms of soy nutritional supplement
      (containing 98% acetyl glucoside isoflavones) were consumed by eight human
      volunteers (three were Asian people and five were British). Their daily urine
      samples were collected before and after a 5-week consumption of supplementation
      period. Conjugated isoflavones of genistein, daidzein and glycitein were
      hydrolyzed by enzyme, extracted with methyl tert-butyl ether and analysed using
      liquid chromatography coupled with electrospray tandem mass spectrometry.
      Daidzein, genistein, glycitein, dihydrogenistein, dihydrodaidzein and O
      desmethylangolensin were identified and quantified simultaneously with high
      recoveries. The levels of free isoflavones and total isoflavones were compared,
      and isoflavone glucuronides were identified much higher than the corresponding
      sulfates or aglycone isoflavones. This method provided the measurement of
      isoflavones with high sensitivity and specificity and simplified the sample pre
      treatment procedure. The limitation of detections of dihydrodaidzein, 3'
      hydroxydaidzein, glycitein, daidzein, genistein, dihydrogenistein and O
      desmethylangolensin were 37, 23.5, 12.2, 15.4, 14.8, 2.20 and 0.31 pmol,
      respectively. Only 0.5 ml of urine sample was needed.

PMID- 17499261
TI  - Chelating ligand-mediated synthesis of hollow ZnS microspheres and its optical
      properties.
AB  - Monodispersed hollow ZnS microspheres have been successfully synthesized by a
      facile ethylenediamine tetraacetic acid (EDTA) mediated hydrothermal route. The
      sizes of the hollow spheres vary from 1.5 to 3.5 microm when the reaction
      temperature varied from 130 to 230 degrees C. The formation of these hollow
      spheres is attributed to the oriented aggregation of ZnS nanocrystals around the
      gas-liquid interface between H(2)S and water. EDTA plays important role as
      chelating ligand and capping reagent, which regulates the release of Zn(2+) ions
      for the formation of ZnS hollow spheres. The products were characterized by X-ray
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), UV-vis spectroscopy, photoluminescence, and Raman spectroscopy.
      The obtained ZnS hollow spheres show a sharp and photostable UV emission
      approximately 370 nm, which is attributed to the recombination process associated
      with interstitial sulfur vacancy.

PMID- 17499262
TI  - Structural ordering of organovermiculite: experiments and modeling.
AB  - The ordering of three different sizes of quaternary ammonium salts (QUATs) has
      been studied with respect to concentration of guests in the host's interlayer
      gallery. From the modeling, we could verify that small molecules of n
      butylammonium salt build a monolayer structure in the vermiculite gallery without
      reference to concentration. On the other hand, the larger molecules of
      dodecyltrimethylammonium and dioctadecyldimethylammonium salts are responsive to
      the numbers of their molecules in the interlayer space of the host, building mono
      or bilayered structures. Supersaturated structure of both QUATs keep an
      arrangement of alkyl chains nearly perpendicular to silicate layers, while only
      saturated samples exhibit tilted alkyl chains in the gallery. The ordering
      changes bring out the calculation of mean crystallite size. Low values of the
      nonbond energy of supersaturated forms predict that those organovermiculites will
      readily exfoliate, e.g., in polymer/clay nanocomposite.

PMID- 17499263
TI  - Cathodic adsorptive stripping voltammetric studies on lamivudine: an
      antiretroviral drug.
AB  - The electrochemical reduction and adsorption of lamivudine, a systemic antiviral
      drug, were studied in a phosphate buffer medium at a hanging mercury drop
      electrode (HMDE). Cyclic voltammetry studies showed one well-defined reduction
      peak in the potential range from -1.2 to -1.8 V under different pH conditions,
      but the best results were obtained at pH 3.4. The reduction was irreversible and
      exhibited diffusion-controlled adsorption. The response was evaluated with
      respect to preconcentration time, pH effect, accumulation potential, accumulation
      time, and scan rate. The number of electrons transferred in the reduction process
      was calculated and the probable reduction mechanism was proposed. A systemic
      study of the experimental parameters that affect the square-wave stripping
      response was carried out and experimental conditions were optimized.

PMID- 17499264
TI  - Dependence of depletion layer thickness on polymer concentration determined by
      Vincent's pragmatic and Donath's electrophoretic theories.
AB  - On the interface of a solid surface and a solution of nonadsorbing polymer there
      exists a depletion layer (DL), where the concentration of polymer segments is
      lower. Donath's electrophoretic theory, based on the decreased viscosity in the
      DL region, allows computing DL thickness from the relative (with and without
      polymer) electrophoretic mobility, the bulk viscosity, and the ionic strength.
      The aim of this work is to check experimentally Donath's nonlinear
      electrophoretic (NLE) theory under the most favorable conditions--liposomes in
      solutions of low-molecular poly(ethylene glycol) (PEG). In order to determine DL
      thickness, the dependence of mobility on viscosity is chosen instead on ionic
      strength. The value obtained from NLE theory is compared with the DL thickness
      calculated by Vincent's pragmatic theory. The conformation-statistical parameters
      are calculated on the base of viscosimetric measurements of PEG solution. The
      results indicate a few shortcomings of NLE theory. The main one is that DL
      thickness does not depend on polymer concentration, a fact that is in discrepancy
      with the prediction of Vincent's theory. The conclusion is that NLE theory
      describes well the experimental dependence of the relative mobility on the bulk
      viscosity, but it is inapplicable to quantitative determination of DL thickness.

PMID- 17499265
TI  - Electrochemical removal of the hazardous dye Reactofix Red 3 BFN from industrial
      effluents.
AB  - The electrochemical treatment of dyestuff from aqueous solution using an iron
      cell was achieved with reduction in chemical oxygen demand (COD) and color with
      high efficiency. Degradation of the azo dye Reactofix Red 3 BFN was carried out
      under different experimental conditions. Electrolysis completely decolorizes the
      effluent with substantial reduction in COD value. The rate kinetics during
      electrolysis was found to be first order. Results show that electrochemical
      reduction is a superior technology for treatment of dyes, as there is no
      simultaneous addition of anions, such as sulfate or chloride.

PMID- 17499266
TI  - New insights into the structure of polyelectrolyte complexes.
AB  - The formation of polyelectrolyte complexes (PECs) from oppositely charged linear
      polyelectrolytes (PELs) was studied using static light scattering at various salt
      concentrations. The PELs used were poly(allylamine hydro chloride) (PAH) and the
      two polyanions poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA).
      Physical characteristics such as the radii of gyration, molecular weights, and
      water contents of the PECs were determined at various molar mixing ratios.
      Despite relatively small differences in chemical structure between PAA and PMAA,
      fairly large differences were detected in these physical characteristics.
      Generally, PECs comprising PMAA were larger and contained more water. Moreover,
      by using cryogenic transmission electron microscopy, transmission microscopy and
      atomic force microscopy, shape and structure of the prepared PECs were
      investigated both in solution and after drying. The PECs were found to be
      spherical in solution and the shape was retained after freeze-drying. PECs
      adsorbed on silica surfaces and dried in air at room-temperature still showed a
      three-dimensional structure. However, the relatively low aspect ratios indicated
      that the PECs collapsed significantly due to interactions with the silica during
      adsorption and drying. At intermediate ionic strengths (1-10 mM), stagnation
      point adsorption reflectometry (SPAR) showed that the adsorption of low charged
      cationic PAH-PAA PECs on silica surfaces increased if the pH value was increased
      from pH 5.5 to 7.5.

PMID- 17499267
TI  - Correlation of oxygen consumption, cytochrome c oxidase, and cytochrome c oxidase
      subunit I gene expression in the termination of larval diapause in the bamboo
      borer, Omphisa fuscidentalis.
AB  - The moth Omphisa fuscidentalis (Lepidoptera, Pyralidae) is a univoltine insect
      with a larval diapause period lasting up to 9 months. We studied changes in O(2)
      consumption in conjunction with cytochrome c oxidase activity and cytochrome c
      oxidase subunit I (cox1) gene expression. O(2) consumption changed within a day,
      showing a supradian rhythm with a ca.12-h cycle at 25 degrees C. During the first
      two-thirds of the diapause period, from October to March, O(2) consumption was
      constant until January and then increased by March. Topical application of
      methoprene, a juvenile hormone analog (JHA), to diapausing larvae terminated the
      diapause and was associated with an increase in O(2) consumption rate at diapause
      termination. In JHA-treated larvae, cytochrome c oxidase activity in fat bodies
      was high at the beginning of the prepupal period and highest at pupation. cox1
      expression in fat bodies displayed a transient peak 8 days after JHA application
      and peaked in the prepupal period. Taken together, our results show that the
      break of diapause by JHA is associated with the activation of cox1, bringing
      about an increase in cytochrome c oxidase activity, followed by an increase in
      O(2) consumption rate.

PMID- 17499269
TI  - Crystal structure analysis of the PHD domain of the transcription co-activator
      Pygopus.
AB  - The Wnt/beta-catenin signaling pathway plays important roles in animal
      development and cancer. Pygopus (Pygo) and Legless (Lgs) are recently discovered
      core components of the Wnt/beta-catenin transcription machinery complex, and are
      crucially involved in the regulation of the transcription of the Arm/beta-catenin
      and T cell factors (TCF). Lgs/Bcl9 functions as an adaptor between Pygo and
      Arm/beta-catenin. Here, we report the first crystal structure of the plant
      homeodomain (PHD) finger of Pygopus (Pygo1 PHD), a Pygo family member, which is
      essential for the association with Lgs/Bcl9. The Pygo1 PHD structure forms a
      canonical PHD finger motif, stabilized by two Zn ions coordinated in a cross
      brace scheme. Surprisingly, the Pygo1 PHD domain forms a dimer in both the
      crystals and solution. This is the first structural evidence for dimerization
      among the known PHD domain structures. The dimer formation occurs by the
      interactions of antiparallel beta-sheets between the symmetry-related beta3
      strands of the monomers. The Pygo1 PHD dimer interface mainly comprises
      hydrophobic residues. Interestingly, some of the interface residues, such as
      Met372, Thr373, Ala376 and Leu380, are reportedly important for the association
      with Lgs/Bcl9 and are also critical for transcriptional activation. The M372A and
      L380D mutants, and several surrounding mutants such as S385A and A386D, showed
      decreased ability to form dimers and to interact with the homology domain 1 (HD1)
      of Lgs/Bcl9. These results suggest that the Pygo1 PHD dimerization is
      functionally important for Lgs/Bcl9 recognition as well as for the regulation of
      the Wnt/beta-catenin signaling pathway.

PMID- 17499268
TI  - Spontaneous myocarditis mimicking human disease occurs in the presence of an
      appropriate MHC and non-MHC background in transgenic mice.
AB  - Most individuals have viral infections at some point in their life, however, only
      few develop autoreactivity to cardiac myosin following infection resulting in
      myocarditis suggesting a genetic predisposition. Most mouse models of myocarditis
      are induced by viral infection or by immunization with cardiac myosin. We
      generated HLA-DR3.Abetao and HLA-DQ8.Abetao transgenic mice in NOD and HLA
      DQ8.Abetao in B10 background to study spontaneous autoimmunity. A high mortality
      was observed in NOD.DQ8 female mice 16 weeks or older. Echocardiography showed
      marked systolic dysfunction. Histopathology of various organs revealed an
      enlarged heart with mononuclear infiltrate consisting of CD4 and Mac-1+ cells and
      myocyte necrosis. The autoimmunity was associated with the presence of
      spontaneous autoreactive T cells and antibodies to cardiac myosin. Serologically,
      mice were negative for all known mouse viruses. NOD.DR3.Abetao, the transgene
      negative littermates, NOD, and B10.DQ8 Abetao mice had no gross or microscopic
      cardiac pathology. Spontaneous cellular and humoral response to cardiac myosin
      suggests that NOD.DQ8 may harbor autoreactive cells that can lead to spontaneous
      myocarditis and dilated cardiomyopathy. HLA-DQ8 is required for the
      predisposition to the spontaneous autoreactivity while NOD background influences
      onset and progression of disease. This model of myocarditis occurs predominantly
      in female mice and may provide insight into the pathogenesis of heart disease in
      women.

PMID- 17499270
TI  - Crystal structures of two Bordetella pertussis periplasmic receptors contribute
      to defining a novel pyroglutamic acid binding DctP subfamily.
AB  - Gram-negative bacteria have developed several different transport systems for
      solute uptake. One of these, the tripartite ATP independent periplasmic transport
      system (TRAP-T), makes use of an extracytoplasmic solute receptor (ESR) which
      captures specific solutes with high affinity and transfers them to their partner
      permease complex located in the bacterial inner membrane. We hereby report the
      structures of DctP6 and DctP7, two such ESRs from Bordetella pertussis. These two
      proteins display a high degree of sequence and structural similarity and possess
      the "Venus flytrap" fold characteristic of ESRs, comprising two globular
      alpha/beta domains hinged together to form a ligand binding cleft. DctP6 and
      DctP7 both show a closed conformation due to the presence of one pyroglutamic
      acid molecule bound by highly conserved residues in their respective ligand
      binding sites. BLAST analyses have revealed that the DctP6 and DctP7 residues
      involved in ligand binding are strictly present in a number of predicted TRAP-T
      ESRs from other bacteria. In most cases, the genes encoding these TRAP-T systems
      are located in the vicinity of a gene coding for a pyroglutamic acid metabolising
      enzyme. Both the high degree of conservation of these ligand binding residues and
      the genomic context of these TRAP-T-coding operons in a number of bacterial
      species, suggest that DctP6 and DctP7 constitute the prototypes of a novel TRAP-T
      DctP subfamily involved in pyroglutamic acid transport.

PMID- 17499271
TI  - When the surface tells what lies beneath: combinatorial phage-display mutagenesis
      reveals complex networks of surface-core interactions in the pacifastin protease
      inhibitor family.
AB  - Pacifastin protease inhibitors are small cysteine-rich motifs of approximately 35
      residues that were discovered in arthropods. The family is divided into two
      related groups on the basis of the composition of their minimalist inner core. In
      group I, the core is governed by a Lys10-Trp26 interaction, while in group II it
      is organized around Phe10. Group I inhibitors exhibit intriguing taxon
      specificity: potent arthropod-trypsin inhibitors from this group are almost
      inactive against vertebrate enzymes. The group I member SGPI-1 and the group II
      member SGPI-2 are extensively studied inhibitors. SGPI-1 is taxon-selective,
      while SGPI-2 is not. Individual mutations failed to explain the causes underlying
      this difference. We deciphered this phenomenon using comprehensive combinatorial
      mutagenesis and phage display. We produced a complete chimeric SGPI-1 / SGPI-2
      inhibitor-phage library, in which the two sequences were shuffled at the highest
      possible resolution of individual residues. The library was selected for binding
      to bovine trypsin and crayfish trypsin. Sequence analysis of the selectants
      revealed that taxon specificity is due to an intra-molecular functional coupling
      between a surface loop and the Lys10-Trp26 core. Five SGPI-2 surface residues
      transplanted into SGPI-1 resulted in a variant that retained the "taxon-specific"
      core, but potently inhibited both vertebrate and arthropod enzymes. An additional
      rational point mutation resulted in a picomolar inhibitor of both trypsins. Our
      results challenge the generally accepted view that surface residues are the
      exclusive source of selectivity for canonical inhibitors. Moreover, we provide
      important insights into general principles underlying the structure-function
      properties of small disulfide-rich polypeptides, molecules that exist at the
      borderline between peptides and proteins.

PMID- 17499272
TI  - Cytochrome P450s and short-chain dehydrogenases mediate the toxicogenomic
      response of PCB52 in the nematode Caenorhabditis elegans.
AB  - Although non-coplanar PCBs are ubiquitous organic chemicals known to induce
      numerous biological responses and thus are toxic to man and wildlife, little is
      known about the toxic mode of action. Using PCB52, an ortho-substituted,
      2,2',5,5'-tetrachlorobiphenyl, it was possible to pinpoint the relationship
      between induced gene expression and observed toxicity in the model nematode
      Caenorhabditis elegans. On the basis of the calculated EC20 for brood size (5
      mg/l), whole genome DNA microarray experiments were performed to identify
      differentially expressed genes. Gene knockdown by RNAi was used to determine the
      consequences in reproductive fitness in the presence and in the absence of PCB52.
      On the basis of altered phenotype, several gene classes were identified to have a
      pivotal role in PCB52 toxicogenesis, most notably cytochrome P450s, short-chain
      dehydrogenases and lipases. In addition to this, four of six selected cytochrome
      P450s were shown to be involved in fat storage, with PCB52 exposure increasing
      the fat content in N2 wild-type as indicated by staining with Nile red.
      Furthermore, exposure to PCB52 induces a general detoxification response via
      small heat-shock proteins and caspases. Our data provide strong evidence of the
      molecular mechanisms that underlie the toxicity of non-coplanar PCBs, and
      confirms that, despite the ability to metabolize PCB, alterations in lipid
      metabolism and storage are major factors that drive the toxic effect of PCB52.

PMID- 17499273
TI  - Identification of a single HNH active site in type IIS restriction endonuclease
      Eco31I.
AB  - Type IIS restriction endonuclease Eco31I is a "short-distance cutter", which
      cleaves DNA strands close to its recognition sequence, 5'-GGTCTC(1/5).
      Previously, it has been proposed that related endonucleases recognizing a common
      sequence core GTCTC possess two active sites for cleavage of both strands in the
      DNA substrate. Here, we present bioinformatic identification and experimental
      evidence for a single nuclease active site. We identified a short region of
      homology between Eco31I and HNH nucleases, constructed a three-dimensional model
      of the putative catalytic domain and validated our predictions by random and site
      specific mutagenesis. The restriction mechanism of Eco31I is suggested by analogy
      to the mechanisms of phage T4 endonuclease VII and homing endonuclease I-PpoI. We
      propose that residues D311 and N334 coordinate the cofactor. H312 acts as a
      general base-activating water molecule for the nucleophilic attack. K337 together
      with R340 and D345 are located in close proximity to the active center and are
      essential for correct folding of catalytic motif, while D345 together with R264
      and D273 could be directly involved in DNA binding. We also predict that the
      Eco31I catalytic domain contains a putative Zn-binding site, which is essential
      for its structural integrity. Our results suggest that the HNH-like active site
      is involved in the cleavage of both strands in the DNA substrate. On the other
      hand, analysis of site-specific mutants in the region, previously suggested to
      harbor the second active site, revealed its irrelevance to the nuclease activity.
      Thus, our data argue against the earlier prediction and indicate the presence of
      a single conserved active site in type IIS restriction endonucleases that
      recognize common sequence core GTCTC.

PMID- 17499274
TI  - Intracellular redistribution of dihydropyridine receptor in the rat heart during
      the progression of sepsis.
AB  - BACKGROUND: Dihydropyridine receptor (DHPR) regulates the rate and force of
      cardiac muscle contraction. This study examined the alteration in the
      intracellular redistribution of DHPR and its association with the development of
      the two distinct cardiodynamic states in the rat heart during the progression of
      sepsis. MATERIAL AND METHODS: Sepsis was induced by cecal ligation and puncture
      (CLP). DHPRs were assayed using [(3)H]PN200-100 binding and photoaffinity
      labeling with [(3)H]azidopine followed by polyacrylamide gel electrophoresis.
      RESULTS: [(3)H]PN200-110 binding shows that during the early hyperdynamic phase
      of sepsis (9 h post-CLP), the Bmax was increased by 27% in sarcolemma while
      decreased by 24% in light vesicle. During the late hypodynamic phase of sepsis
      (18 h post-CLP), the Bmax was decreased by 39% in sarcolemma but increased by 59%
      in light vesicle. The sum of the Bmax for both membrane fractions was increased
      by 16% during early sepsis while decreased by 17% during late sepsis.
      Photoaffinity labeling shows that the incorporation of [(3)H]azidopine into 165
      kDa peptides during early sepsis was increased by 28% in sarcolemma whereas
      decreased by 23% in light vesicle. During late sepsis, the incorporation was
      decreased by 38% in sarcolemma but increased by 46% in light vesicle. The sum of
      the 165 kDa peptides for both membrane fractions was increased by 13% during
      early while decreased by 13% during late sepsis. CONCLUSIONS: These data indicate
      that DHPRs in the rat heart were externalized from light vesicles to sarcolemma
      during the early hyperdynamic phase whereas they were internalized from surface
      membranes to intracellular sites during the late hypodynamic phase of sepsis.
      Furthermore, DHPRs were overexpressed during early sepsis while they were
      underexpressed during late sepsis. Alterations in the expression and
      intracellular redistribution of DHPRs may contribute to the development of the
      biphasic cardiodynamic states during the progression of sepsis.

PMID- 17499275
TI  - A single center experience in minimally invasive treatment of postcholecystectomy
      bile leak, complicated with biloma formation.
AB  - BACKGROUND: Bilomas are localized collections of bile occurring usually post
      operatively from an injured cystic or bile duct. Our study aims to evaluate the
      efficacy of minimal access endoscopic and percutaneous modalities in treating
      symptomatic bile leak and biloma formation. PATIENTS AND METHODS: Sixteen
      patients with biloma after open or laparoscopic cholecystectomy underwent
      assessment of the site and extent of the bile leak via endoscopic retrograde
      cholangiography (ERC). Endoscopic sphincterotomy was performed in all patients
      who were managed non-operatively, any retained duct stones were removed, and an
      endoprosthesis was inserted in a selected basis. Percutaneous drainage of the
      bile collection, under ultrasound or computed tomography guidance, followed ERC.
      RESULTS: ERC supplemented by computed tomography or ultrasound guided
      percutaneous biloma drainage was successful in 15 patients. One patient having
      major ductal injury was treated surgically. Thirteen patients had leakage from
      the cystic duct, one from the right hepatic duct, and one from an aberrant right
      hepatic duct. Bile duct stones were removed from seven patients an endoprosthesis
      was inserted in six and a nasobilary catheter in one. Bilomas resolved and bile
      leakage was treated successfully in all 15 patients with no further
      complications. CONCLUSION: ERC accurately diagnoses the cause of
      postcholecystectomy bile leakage and biloma formation. Furthermore, endoscopic
      sphincterotomy and selective stent insertion in coordination with percutaneous
      drainage procedures represents in the majority of cases the corner stone of a
      definitive treatment.

PMID- 17499276
TI  - Modelling calcium microdomains using homogenisation.
AB  - Microdomains of calcium (i.e., areas on the nanometer scale that have
      qualitatively different calcium concentrations from that in the bulk cytosol) are
      known to be important in many situations. In cardiac cells, for instance, a
      calcium microdomain between the L-type channels and the ryanodine receptors, the
      so-called diadic cleft, is where the majority of the control of calcium release
      occurs. In other cell types that exhibit calcium oscillations and waves, the
      importance of microdomains in the vicinity of clusters of inositol trisphosphate
      receptors, or between the endoplasmic reticulum (ER) and other internal
      organelles or the plasma membrane, is clear. Given the limits of computational
      power, it is not currently realistic to model an entire cellular cytoplasm by
      incorporating detailed structural information about the ER throughout the entire
      cytoplasm. Hence, most models use a homogenised approach, assuming that both
      cytoplasm and ER coexist at each point of the domain. Conversely, microdomain
      models can be constructed, in which detailed structural information can be
      incorporated, but, until now, methods have not been developed for linking such a
      microdomain model to a model at the level of the entire cell. Using the
      homogenisation approach we developed in an earlier paper [Goel, P., Friedman, A.,
      Sneyd, J., 2006. Homogenization of the cell cytoplasm: the calcium bidomain
      equations. SIAM J. Multiscale Modeling Simulation, in press] we show how a
      multiscale model of a calcium microdomain can be constructed. In this model a
      detailed model of the microdomain (in which the ER and the cytoplasm are separate
      compartments) is coupled to a homogenised model of the entire cell in a rigorous
      way. Our method is illustrated by a simple model of the diadic cleft of a cardiac
      half-sarcomere.

PMID- 17499277
TI  - Population based incidence and age distribution of spermatocytic seminoma.
AB  - PURPOSE: Spermatocytic seminoma is a rare subtype of testicular germ cell tumor
      which has been reported to occur in elderly men. We report the first population
      based estimate of incidence, temporal trends and age distribution of this tumor.
      MATERIALS AND METHODS: All cases of primary testicular cancer identified by
      cancer registries in Australia between 1982 and 2002 were available for analysis.
      The International Classification of Diseases for Oncology code M-9063/3 was used
      to identify spermatocytic seminomas. Incidence trends were modeled using Poisson
      regression. RESULTS: There were 58 cases of spermatocytic seminoma out of 9,658
      cases of primary malignant testicular neoplasms identified by the cancer
      registries. This tumor comprised 1.1% of all seminoma and the age standardized
      incidence rate was 0.4 per million (95% CI 0.3-0.6). A temporal increase in
      incidence was found but not one reaching statistically significance. Age at
      diagnosis ranged from 19 to 92 years with a mean of 53.5 (SD 16.7) and a median
      of 54 years. CONCLUSIONS: Spermatocytic seminoma should be considered in the
      differential diagnosis for testicular germ cell tumors presenting in young adults
      because this tumor occurs as often in men younger than 55 years as it does in
      older men. Although rare, the occurrence of this tumor is not as singular as the
      current literature suggests.

PMID- 17499279
TI  - Urachal carcinoma: contemporary surgical outcomes.
AB  - PURPOSE: We determined surgical outcomes in a contemporary series of patients who
      underwent surgery for urachal carcinoma. MATERIALS AND METHODS: A cohort of 50
      patients with clinically staged localized urachal carcinoma underwent extended
      partial cystectomy, including the urachal tumor mass and entire urachus. The
      patients were followed a median of 5+ years for cancer-free survival. RESULTS: Of
      the 50 patients 93% (26 of 28) with tumor confined to the urachus and bladder
      survived compared to 69% (9 of 13) with extravesical or peri-urachal tumor
      invasion and none (9 patients) with tumor invasion into the peritoneal cavity.
      Local recurrence was noted in 9 patients (18%) and 2 had salvage therapy. The
      most significant predictors of survival were pathological tumor stage and
      negative surgical margins. CONCLUSIONS: Wide resection of the tumor mass and
      entire urachus resulting in negative soft tissue and bladder margins cures the
      majority of nonmetastatic urachal cancers.

PMID- 17499280
TI  - Clinical judgment analysis of the parameters used by consultant urologists in the
      management of prostate cancer.
AB  - PURPOSE: We assessed which clinical parameters consultant urologists use to
      recommend treatment for early prostate cancer. MATERIALS AND METHODS: A total of
      30 consultant urologists reviewed 70 paper representations of patients with
      prostate cancer. Each contained 7 commonly available cues, including prostate
      specific antigen, Gleason grade, rectal examination, magnetic resonance
      imaging/laparoscopic stage, medical history, patient choice and age, in addition
      to 2 cues not yet routinely available, that is predicted life expectancy and 10
      year survival probability, as calculated using actuarial formulas based on
      noncancer comorbidity. Consultants indicated how strongly they would recommend
      radical prostatectomy, radiotherapy with or without hormones, or active
      surveillance/hormones. Judgment analysis was performed using multiple regression
      analysis with significance considered at p<or=0.01 to identify which cues
      consultants had used. RESULTS: Consultants varied in the treatments that they
      recommended. An average of only 3 of the possible 9 cues was used to formulate
      decisions. Prostate specific antigen and predicted 10-year survival probability
      were most commonly used for recommending all 3 treatment options. Patient choice,
      predicted life expectancy, rectal examination and age were all used infrequently.
      Consultants were inconsistent in an average of 31.4% of judgments when repeat
      cases were analyzed with the greatest inconsistency observed when recommending
      radiotherapy with or without hormones and the least inconsistency when
      recommending radical prostatectomy. CONCLUSIONS: Consultants were inconsistent in
      their decisions regarding the management of early prostate cancer and they used
      only a small number of available clinical parameters. Ensuring that all relevant
      information is available and providing clinicians with further education and
      training would ensure that treatment decisions become more reliable, appropriate
      and targeted toward patient choice.

PMID- 17499283
TI  - A phase III, multicenter comparison of hexaminolevulinate fluorescence cystoscopy
      and white light cystoscopy for the detection of superficial papillary lesions in
      patients with bladder cancer.
AB  - PURPOSE: We compared hexaminolevulinate fluorescence cystoscopy with white light
      cystoscopy for detecting Ta and T1 papillary lesions in patients with bladder
      cancer. MATERIALS AND METHODS: A total of 311 patients with known or suspected
      bladder cancer underwent bladder instillation with 50 ml 8 mM HAL for 1 hour. The
      bladder was inspected using white light cystoscopy, followed by blue light
      (fluorescence) cystoscopy. Papillary lesions were mapped and resected for
      histological examination. RESULTS: Noninvasive pTa tumors were found in 108 of
      196 evaluable patients (55.1%). In 31 patients (29%) at least 1 more tumor was
      detected by HAL than by white light cystoscopy (p<0.05). Six of these patients
      had no lesions detected by white light, 12 had 1 lesion detected by white light
      and more than 1 by HAL, and 13 had multiple Ta lesions detected by the 2 methods.
      Conversely at least 1 more tumor was detected by white light cystoscopy than by
      HAL cystoscopy in 10 patients (9%, 95% CI 5-16). Tumors invading the lamina
      propria (T1) were found in 20 patients (10.2%). At least 1 additional T1 tumor
      was detected by HAL but not by white light cystoscopy in 3 of these patients
      (15%), while at least 1 more T1 tumor was detected by white light cystoscopy than
      by HAL cystoscopy in 1 patient (5%, 95% CI 0-25). Detection rates for Ta tumors
      were 95% for HAL cystoscopy and 83% for white light cystoscopy (p=0.0001).
      Detection rates were 95% and 86%, respectively, for T1 tumors (p=0.3). HAL
      instillation was well tolerated with few local or systemic side effects.
      CONCLUSIONS: HAL fluorescence cystoscopy detected at least 1 more Ta and T1
      papillary tumor than white light cystoscopy in approximately a third of the
      patients with such tumors. Whether this would translate to improved patient
      outcomes has yet to be determined.

PMID- 17499284
TI  - Finasteride decreases the risk of prostatic intraepithelial neoplasia.
AB  - PURPOSE: High grade prostatic intraepithelial neoplasia is likely a premalignant
      lesion of the prostate. Decreasing the frequency of high grade PIN may decrease
      the risk of prostate cancer. In the Prostate Cancer Prevention Trial we evaluated
      the impact of finasteride on the risk of a needle biopsy diagnosis of high grade
      prostatic intraepithelial neoplasia. MATERIALS AND METHODS: The Prostate Cancer
      Prevention Trial was a randomized, placebo controlled clinical trial that
      enrolled 18,882 men without evidence of prostate cancer, prostate specific
      antigen less than 3.0 ng/ml and normal digital rectal examination, and randomized
      them to 5 mg finasteride daily or placebo. Subjects were followed for 7 years
      with biopsy recommended for prostate specific antigen greater than 4.0 ng/ml,
      adjusted in the finasteride group to achieve an equal number of biopsy
      recommendations or for abnormal digital rectal examination. All cancer-free
      subjects were recommended to undergo biopsy after 7 years on study. We evaluated
      the diagnosis of high grade prostatic intraepithelial neoplasia with or without
      concomitant prostate cancer in these 2 study groups. RESULTS: The number of men
      evaluable for high grade prostatic intraepithelial neoplasia was 4,568 in the
      finasteride group and 4,886 in the placebo group. High grade prostatic
      intraepithelial neoplasia alone was diagnosed in 276 men (6.0%) in the
      finasteride group vs 347 (7.1%) in the placebo group (RR 0.85, 95% CI 0.73-0.99,
      p=0.04). High grade prostatic intraepithelial neoplasia accompanied by prostate
      cancer was diagnosed in 144 men (3.2%) in the finasteride group vs 223 (4.6%) in
      the placebo group (RR 0.69, 95% CI 0.56-0.85, p=0.0004). Finasteride
      significantly decreased the overall risk of high grade prostatic intraepithelial
      neoplasia (alone and with cancer) from 570 cases (11.7%) in the placebo group to
      420 (9.2%) in the finasteride group (HR 0.79, 95% CI 0.70-0.89, p<0.001).
      CONCLUSIONS: Finasteride significantly decreased the risk of high grade PIN. This
      observation may explain how finasteride decreased prostate cancer in the Prostate
      Cancer Prevention Trial, supporting the notion that high grade prostatic
      intraepithelial neoplasia is a premalignant lesion of the prostate, and it
      provides new information relevant to the consideration of finasteride for
      prostate cancer prevention.

PMID- 17499285
TI  - Results of cystocele repair: a comparison of traditional anterior colporrhaphy,
      polypropylene mesh and porcine dermis.
AB  - PURPOSE: Because traditional anterior colporrhaphy can have a high recurrence
      rate, we assessed the recurrence rate of 3 methods of cystocele repair, including
      1) traditional anterior colporrhaphy, 2) repair using porcine dermis
      interposition graft and 3) repair using polypropylene mesh. Additionally, we
      compared the rate of erosion of porcine dermal graft with that of polypropylene
      mesh. MATERIALS AND METHODS: The records of patients who underwent cystocele
      repair by the same urologist using porcine dermal graft, polypropylene mesh or
      traditional repair from January 1999 to August 2005 were reviewed. Data were
      collected on history, physical examination, outcomes and complications. Using the
      Baden-Walker system a cystocele of grade 2 or higher on followup examination was
      considered recurrence. RESULTS: A total of 119 patients underwent cystocele
      repair from January 1999 to August 2005. Followup was available on 99 patients
      and it averaged 13.5 months (range 2 to 46). Of the patients 56 (57%) underwent
      cystocele repair using porcine dermal graft, 25 (25%) received polypropylene mesh
      and 18 (18%) underwent traditional repair. Of the 99 patients 22 (22%) had
      cystocele recurrence. Based on the type of repair 36% of patients (20 of 56) with
      porcine dermal grafts had recurrence compared to 4% (1 of 25) and 6% (1 of 18)
      using polypropylene and traditional repair, respectively. Mean time to cystocele
      recurrence was 4.9 months (range 0.5 to 20). A total of 12 patients (21%) had
      extrusion of porcine grafts through the anterior vaginal wall incision compared
      to 1 (4%) with polypropylene mesh. CONCLUSIONS: In our patient population the
      short-term failure rate for anterior vaginal wall prolapse using porcine dermis
      interposition graft was higher than that for traditional anterior colporrhaphy or
      polypropylene mesh. In addition, the incidence of vaginal extrusion of porcine
      graft was unacceptably high. Porcine dermis is a less suitable material for
      cystocele repair than polypropylene mesh or traditional anterior colporrhaphy.
      Prospective, randomized trials are necessary to determine the true efficacy and
      complication rates of these graft materials for anterior vaginal wall prolapse
      repair.

PMID- 17499287
TI  - Combined prednisone and mycophenolate mofetil treatment for retroperitoneal
      fibrosis.
AB  - PURPOSE: We determined the efficacy of a combination of corticosteroids and
      mycophenolate mofetil for retroperitoneal fibrosis. MATERIALS AND METHODS: We
      performed a prospective observational study of the treatment of 7 patients with
      biopsy proven retroperitoneal fibrosis. Patients were treated with 40 mg
      prednisone daily with a gradual taper over 6 months. Mycophenolate mofetil was
      administered at a starting dose of 1,000 mg twice daily and continued for 6
      months following resolution of systemic symptoms and extubation of affected
      ureters. Outcomes included normalization of laboratory evidence of inflammation,
      regression of fibrosis by computerized tomography and the ability to discontinue
      ureteral stents. RESULTS: Seven patients were treated with mycophenolate mofetil
      and prednisone. Five of the 7 patients had bilateral ureteral obstruction and 1
      had unilateral obstruction requiring ureteral stents. Baseline and followup
      laboratory values were C-reactive protein 8.9 and 1.3 mg/dl (p=0.07), hemoglobin
      10.7 and 12.7 gm/dl (p=0.001), erythrocyte sedimentation rate 76 and 14.5 mm per
      hour (p=0.015) and serum creatinine 3.32 and 1.08 mg/dl (p=0.07), respectively.
      Six of the 7 patients had a mean 32% regression of the retroperitoneal mass on
      computerized tomography. Ten of the 11 obstructed ureters were free of
      obstruction following ureteral stent removal. The mean time to stent removal was
      10.5 months. One patient had a distal ureteral stricture and continued to require
      decompression. There were no treatment related side affects. CONCLUSIONS:
      Mycophenolate mofetil combined with prednisone was safe and efficacious in this
      small cohort of patients with retroperitoneal fibrosis. Larger trials are needed
      to confirm these results.

PMID- 17499288
TI  - Under diagnosis and over diagnosis of prostate cancer in a screening population
      with serum PSA 2 to 10 ng/ml.
AB  - PURPOSE: Since the implementation of widespread serum total prostate specific
      antigen based screening, the risk of prostate cancer over diagnosis has become a
      concern. We evaluated the amount of possible over and under diagnosis of prostate
      cancer in an asymptomatic screening population with a total prostate specific
      antigen of 2.0 to 3.9 (lower range) and 4.0 to 10.0 ng/ml (higher range).
      MATERIALS AND METHODS: A total of 680 patients with prostate cancer were
      included. Possible over diagnosis was defined as Gleason score less than 7,
      pathological stage pT2a and negative surgical margins. Under diagnosis was
      defined as pathological stage pT3 or greater, or positive surgical margins.
      Furthermore, insignificant tumors according to the Epstein criteria were
      evaluated in a small subset of patients for whom cancer volume information was
      available. RESULTS: In the lower and higher total prostate specific antigen
      ranges there was an over diagnosis rate of 19.7% and 16.5%, and an under
      diagnosis rate of 18.9%* and 36.7%, respectively (p<0.05). In the prostate
      specific antigen range of 2.0 to 10.0 ng/ml combined the rates of over and under
      diagnosis were 17.6% and 30.3%, respectively. In addition, 8.7% of tumors with
      total prostate specific antigen 2.0 to 10.0 ng/ml met the Epstein criteria for
      insignificance. CONCLUSIONS: These data show that the reported estimates of over
      diagnosis in the low total prostate specific antigen group are exaggerated in a
      screening population. Using our criteria prostate cancer under diagnosis occurs
      more frequently than over diagnosis in the total prostate specific antigen range
      of 4.0 to 10 ng/ml.

PMID- 17499289
TI  - Effect of prostate volume on tumor grade in patients undergoing radical
      prostatectomy in the era of extended prostatic biopsies.
AB  - PURPOSE: We investigated the influence of prostate volume on biopsy and
      prostatectomy Gleason score, the incidence of upgrading and total tumor volume.
      MATERIALS AND METHODS: From 1997 to 2004, 247 patients were diagnosed with
      prostate cancer by multisite extended prostatic biopsy (10 or 11 cores) and
      underwent radical prostatectomy at our institution without neoadjuvant therapy.
      Medical records were reviewed to determine patient age at diagnosis, preoperative
      prostate specific antigen, prostate volume, clinical stage, biopsy Gleason score,
      pathological stage, prostatectomy Gleason score and total tumor volume. The Mann
      Whitney and chi-square tests were used to compare variables among groups and
      multivariate regression analysis was used to determine predictors of Gleason
      score. RESULTS: Median patient age was 61 years and median preoperative prostate
      specific antigen was 5.5 ng/ml. Median prostate volume on transrectal ultrasound
      was 37 cc. Prostatectomy Gleason score was 6 in 31% of cases, 7 in 57% and 8-9 in
      12%. Prostate volume greater than 50 cc was significantly associated with a
      higher incidence of well differentiated tumors (Gleason score 6) at
      prostatectomy, that is 17.9% in patients with a prostate volume of 25 cc or less,
      28.9% in those with a prostate volume of 25 to 50 cc and 45.3% in those with a
      prostate volume of greater than 50 cc (p<0.01). In addition, the incidence of
      tumor upgrading was significantly lower in patients with a large prostate volume
      (greater than 50 cc) compared to that in those with a smaller prostate volume
      (20.8% vs 36.1%, p<0.05), particularly in the subset with biopsy Gleason score 6
      (24% vs 54.1%, p<0.01). Patients with a large prostate volume (greater than 50
      cc) had smaller total tumor volume with a trend toward statistical significance
      (median total tumor volume 0.86 vs 1.1 cc, p=0.0631). CONCLUSIONS: In the era of
      extended prostatic biopsies patients with a large prostate volume have a
      significantly higher incidence of well differentiated tumor at prostatectomy and
      a lower likelihood of tumor upgrading.

PMID- 17499291
TI  - A comparison of hexaminolevulinate fluorescence cystoscopy and white light
      cystoscopy for the detection of carcinoma in situ in patients with bladder
      cancer: a phase III, multicenter study.
AB  - PURPOSE: We compared hexaminolevulinate (Hexvix) fluorescence cystoscopy with
      white light cystoscopy for detecting carcinoma in situ. MATERIALS AND METHODS: In
      this multicenter study 298 patients with known or suspected bladder cancer
      underwent bladder instillation with 50 ml 8 mM hexaminolevulinate for 1 hour.
      Cystoscopy was then performed, first using standard white light and then
      hexaminolevulinate fluorescence cystoscopy. Lesions or suspicious areas
      identified under the 2 illumination conditions were mapped and biopsied for
      histological examination. In addition, 1 directed biopsy was obtained from an
      area appearing to be normal. RESULTS: Of 196 evaluable patients 29.6% (58 of 196)
      had carcinoma in situ, including 18 with carcinoma in situ alone, and 35 with
      carcinoma in situ and concomitant papillary disease, which was only detected on
      random biopsy in 5. Of the 18 patients with no concomitant papillary disease
      carcinoma in situ was detected only by hexaminolevulinate fluorescence in 4 and
      only by white light in 4. In the group with concomitant papillary disease
      carcinoma in situ was found only by hexaminolevulinate fluorescence in 5 patients
      and only by white light in 3. The proportion of patients in whom 1 or more
      carcinoma in situ lesions were found only by hexaminolevulinate cystoscopy was
      greater than the hypothesized 5% (p=0.0022). Overall more carcinoma in situ
      lesions were found by hexaminolevulinate than by white light cystoscopy in 22 of
      58 patients (41.5%), while the converse occurred in 8 of 58 (15.1%). Biopsy
      results confirmed cystoscopy findings. Of a total of 113 carcinoma in situ
      lesions in 58 patients 104 (92%) were detected by hexaminolevulinate cystoscopy
      and 77 (68%) were detected by white light cystoscopy, while 5 were detected only
      on directed visually normal mucosal biopsy. Hexaminolevulinate instillation was
      well tolerated with no local or systemic side effects. CONCLUSIONS: In patients
      with bladder cancer hexaminolevulinate fluorescence cystoscopy with blue light
      can diagnose carcinoma in situ that may be missed with white light cystoscopy.
      Hexaminolevulinate fluorescence cystoscopy can be used in conjunction with white
      light cystoscopy to aid in the diagnosis of this form of bladder cancer.

PMID- 17499292
TI  - Does the intrarectal instillation of lidocaine gel before periprostatic
      neurovascular bundle block during transrectal ultrasound guided prostate biopsies
      improve analgesic efficacy? A prospective, randomized trial.
AB  - PURPOSE: We assessed the analgesic effect of additional intrarectal lidocaine gel
      instillation during transrectal ultrasound guided prostate biopsy and identified
      the procedural steps that benefit from lidocaine gel instillation. MATERIALS AND
      METHODS: A total of 250 consecutive patients scheduled for prostate biopsy were
      randomized into 2 groups. In the 125 group 1 patients lidocaine gel was instilled
      intrarectally before periprostatic neurovascular bundle block. The 125 patients
      in group 2 underwent only periprostatic neurovascular bundle block without
      lidocaine gel instillation. Of the 250 patients 90 in group 1 and 113 in group 2,
      in whom 12 systematic cores were obtained, were enrolled for data analysis. Pain
      was assessed using a visual analog scale during periprostatic neurovascular
      bundle block (visual analog scale 1), during biopsy (visual analog scale 2) and
      20 minutes after biopsy (visual analog scale 3). Differences between the visual
      analog scale scores of the 2 groups at each procedural step were evaluated using
      the unpaired t test with p<0.05 considered significant. RESULTS: In terms of pain
      experienced during the 3 procedural steps scores were significantly different
      during biopsy (p<0.01). Visual analog scale scores of patients in group 1 showed
      a tendency to be lower than the scores of patients in group 2 during
      periprostatic neurovascular bundle block and 20 minutes after biopsy (p=0.11 and
      0.20, respectively). CONCLUSIONS: Intrarectal lidocaine gel instillation before
      periprostatic neurovascular bundle block produces a significant additional
      analgesic effect during biopsy. The procedure is simple, safe and rapid, and it
      should be considered in all patients undergoing transrectal ultrasound guided
      prostate biopsy.

PMID- 17499293
TI  - Is routine digital rectal examination required for the followup of prostate
      cancer?
AB  - PURPOSE: With more men being diagnosed and radically treated for prostate cancer
      there is an increasing number of patients requiring followup. A proportion of
      radically treated patients have recurrence and require early salvage treatment.
      Traditionally followup involved physical examination, urinalysis, imaging and
      biopsy. Since the development of the prostate specific antigen assay, followup
      has largely consisted of digital rectal examination and prostate specific antigen
      determination. Although digital rectal examination is routinely used, its
      efficacy for detecting recurrent cancer in the absence of biochemical evidence of
      disease progression was questioned in recent studies. MATERIALS AND METHODS: We
      performed a literature search using the key words digital rectal examination, per
      rectal examination, radical prostatectomy and radical radiotherapy, and cross
      referenced all results. RESULTS: The literature that supports digital rectal
      examination as part of patient followup after radical prostatectomy is based on
      case studies and it is less applicable with more sensitive prostate specific
      antigen assays. In almost 5,000 patients after prostatectomy a prostate specific
      antigen increase reliably preceded disease recurrence, making digital rectal
      examination superfluous to requirements. No published literature supports repeat
      digital rectal examination after radical radiotherapy. CONCLUSIONS: Prostate
      specific antigen allows the early detection of disease recurrence. Although
      digital rectal examination is widely used to follow patients, contemporary
      studies consistently show that disease progression does not occur in the absence
      of increasing prostate specific antigen. This suggests that remote followup of
      patients with prostate specific antigen alone is a safe practice, although
      caution should be exercised in those with higher grade tumors, which may not
      produce significant amounts of prostate specific antigen.

PMID- 17499294
TI  - Decrease in racial disparities in the staging evaluation for prostate cancer
      after publication of staging guidelines.
AB  - PURPOSE: We compared how men with incident prostate cancer were staged before and
      after the 1995 publication of National Comprehensive Cancer Network, American
      Urological Association and American College of Radiology staging guidelines, and
      determined whether there were racial differences in the staging evaluation.
      MATERIALS AND METHODS: We performed a retrospective cohort study of the use of
      bone scan and pelvic imaging (pelvic computerized tomography or magnetic
      resonance imaging) in 96,986 men with incident prostate cancer from 1991 to 1994
      compared to 1995 to 1999 from Surveillance, Epidemiology and End Results-Medicare
      linked data files. RESULTS: During 1991 to 1994 bone scan was done in 83.1% and
      73.7% of men who would and would not have met guideline criteria for staging,
      respectively. From 1995 to 1999 bone scan use decreased slightly in men who met
      guideline criteria (74.4%) but it decreased substantially in men who did not meet
      guideline criteria (55.2%). Between 1991 to 1994 and 1995 to 1999 rates of pelvic
      imaging increased for men who did and decreased for men who did not meet
      guideline criteria for staging (45.5% to 57.2% and 48.4% to 41.5%, respectively).
      On multivariate analysis in men who did not meet guideline criteria there was no
      change in the association between the use of staging tests and race from 1991 to
      1994, to 1995 to 1999. However, of men who met guideline criteria for staging
      black men were less likely to undergo bone scan and less likely to undergo pelvic
      imaging than white men diagnosed in 1991 to 1994 but this racial difference was
      not seen during 1995 to 1999. CONCLUSIONS: Using a population based cohort this
      study reveals a decrease in racial disparity and an increase in evidence based
      use of staging tests in men with incident prostate cancer in the period after the
      publication of National Comprehensive Cancer Network, American Urological
      Association and American College of Radiology guidelines.

PMID- 17499297
TI  - Bilateral testicular germ cell tumors in Turkey: increase in incidence in last
      decade and evaluation of risk factors in 30 patients.
AB  - PURPOSE: The relative risk of germ cell testicular tumor is significantly higher
      in patients with a testicular tumor history. We reviewed histological and
      clinical features in 30 patients with bilateral tumors treated at 2 academic
      centers in Turkey. MATERIALS AND METHODS: Of 987 patients with testicular germ
      cell tumors 30 (3.0%) were diagnosed with bilateral disease. Data on clinical
      information, histopathology and followup records were reevaluated. Contralateral
      testis biopsy was not performed in any patient at initial orchiectomy. RESULTS:
      Of 30 patients 24 had sequential tumors at a median interval of 75 months (range
      3 to 260) and 6 (20.0%) had synchronous tumors. Mean age at presentation was 32.3
      and 26.7 years, respectively. The second tumor occurred within 2 and 5 years in
      20.8% and 41.7% of patients, respectively. Patients with seminoma were at
      significantly higher risk for bilateral disease (4.5% vs 2.3%), whereas patients
      with nonseminoma had more advanced disease at presentation. Synchronous tumors
      had similar tumor histology on each side and more advanced stage at presentation
      than metachronous tumors. Most patients with metachronous tumors had stage 1
      disease, including 81% originally and 95.2% subsequently. Primary tumors were
      significantly larger than secondary tumors (4.78 vs 2.59 cm). Median time after
      the first and second germ cell tumors was 128 and 47 months, respectively. At
      last followup all patients had no evidence of disease. CONCLUSIONS: The risk of
      contralateral testicular germ cell tumor in patients with seminoma was 2 times
      higher than in those without a history of tumor. Synchronous tumors present at
      advanced stage and have similar histology on each side. Clinical outcome is
      excellent with appropriate treatment. Contralateral testis biopsy at initial
      diagnosis is not mandatory.

PMID- 17499298
TI  - Application of self-expandable metal stents for ureteroileal anastomotic
      strictures: long-term results.
AB  - PURPOSE: We report our long-term experience with the management of benign
      ureteroileal anastomotic strictures using self-expandable metal stents. MATERIALS
      AND METHODS: A total of 16 male and 2 female patients with a mean+/-SD age of
      72+/-7 years (range 66 to 78) with benign fibrotic strictures at the site of
      ureteroileal anastomosis underwent implantation of self-expandable metal stents
      with a nominal diameter of 6 to 8 mm. A total of 24 ureteroileal conduits were
      treated. The external nephrostomy tubes were removed after fluoroscopic
      validation of ureteral patency. Patients were followed with blood biochemistry,
      ultrasonography, urography and/or virtual endoscopy. Retrograde external-internal
      catheter insertion through the cutaneous stoma was performed in cases of
      recalcitrant stricture. RESULTS: The technical success rate of ureteroileal
      stricture crossing and stenting was 100% (24 of 24 cases). Mean followup was 21
      months (range 7 to 50). The clinical success rate during the immediate post
      stenting period was 70.8% (17 of 24 cases). The 1 and 4-year primary patency
      rates were 37.8% and 22.7%, respectively. Secondary interventions included repeat
      balloon dilation in 15 ureters, of which 8 also underwent subsequent coaxial
      stent placement. The 1 and 4-year secondary patency rates were 64.8% and 56.7%,
      respectively. Except in 2 patients who died external-internal Double-J catheters
      continued to be inserted retrograde in 6 ureteroileal conduits. They are
      periodically exchanged to prevent mucous inspissation and stent encrustation.
      CONCLUSIONS: Metal stents served as the definitive treatment for stricture in
      more than half of the cases, whereas in the remainder the stents allowed the
      uncomplicated and regular exchange of Double-J catheters in retrograde fashion.
      This combined, less invasive treatment for ureteroileal anastomotic strictures
      may help patients avoid surgical revision and preserve quality of life.

PMID- 17499300
TI  - Malignant ureteral obstruction: outcomes after intervention. Have things changed?
AB  - PURPOSE: We reviewed the clinical outcome for patients who underwent
      decompression of malignant ureteral obstruction by analyzing potential prognostic
      factors, technical success, complication rates and days spent in hospital.
      MATERIALS AND METHODS: Retrospective analysis of 102 patients who underwent
      decompression for malignant ureteral obstruction from 1991 to 2003 was performed.
      Data on overall survival, prognostic factors, technical failure, complications
      and days of hospitalization after decompression were examined. RESULTS: Median
      overall survival was 6.8 months (95% CI 4.8-9.3) and the overall survival rate at
      12 months was 29% (95% CI 21%-39%). Univariate analyses found inferior overall
      survival associated with patients having metastases (p=0.041), undergoing
      nephrostomy (p=0.046), prior treatment for cancer (p=0.024) and diagnosis of
      malignant ureteral obstruction in previously established malignancy (p=0.043).
      After multivariate analysis poor prognostic factors were presence of metastases
      (p=0.020) and diagnosis of malignant ureteral obstruction in previously
      established malignancy (p=0.039). Unfavorable cohorts with 3 or 4 unfavorable
      baseline risk factors had an inferior overall survival (p=0.008) with 12-month
      overall survival rates of 12% to 19%. Initial decompression of malignant ureteral
      obstruction failed in 6% of patients (95% CI 2%-12%) and complications were
      experienced by 53% (95% CI 43%-63%). Patients were more likely to experience a
      complication if they had therapy after decompression (p=0.03). The median
      percentage of their remaining lifetime spent in hospital was 17.4% (range 0.21%
      to 100%). CONCLUSIONS: The overall survival of patients with malignant ureteral
      obstruction remains poor. Prognostic factors for decreased overall survival and
      prolonged hospital stay have been identified. Although the technical success of
      decompression has improved the subsequent complication rate is still high.

PMID- 17499302
TI  - Percutaneous nephrolithotripsy with the patient in a modified supine position.
AB  - PURPOSE: The supine position has potential advantages over the prone position for
      percutaneous nephrolithotripsy but it is neglected by most urologists. We
      analyzed the efficacy and safety of percutaneous nephrolithotripsy with the
      patient in a modified supine position. MATERIALS AND METHODS: In a prospective
      study 88 consecutive patients underwent percutaneous nephrolithotripsy in a
      modified supine position. Mean+/-SD stone size was 3.6+/-1.9 cm and 26 patients
      (29.5%) had complete staghorn stones. Ten patients (11.4%) also had ureteral
      stones and underwent concomitant ureteroscopy. Complications and success rates
      were analyzed. RESULTS: The lower, middle and upper calix was the only access in
      42 (47.7%), 10 (11.4%) and 5 patients (5.7%), respectively. Four patients (4.5%)
      had supracostal access. A single percutaneous nephrolithotripsy session was
      needed in 78 patients (88.6%), while 10 (11.4%) required 2 sessions. A total of
      62 patients (70.5%) were stone-free. Five patients (5.7%) required blood
      transfusion. Postoperative complications included ureteral obstruction due to
      migration of stones in 3 cases (3.4%), serious bleeding requiring arterial
      embolization in 2 (2.3%) and prolonged fever in 4 (4.5%). The need for direct
      access to the upper pole and the need for concomitant ureteroscopy did not affect
      the success and complication rates of percutaneous nephrolithotripsy. The colon
      was never damaged and we had no cases of hydrothorax, kidney loss or sepsis.
      CONCLUSIONS: Percutaneous nephrolithotripsy with the patient in a modified supine
      position is effective and safe. It may be considered for most patients requiring
      percutaneous nephrolithotripsy, especially if concomitant ureteroscopy is
      planned.

PMID- 17499304
TI  - Auricular acupressure as a treatment for anxiety before extracorporeal shock wave
      lithotripsy in the elderly.
AB  - PURPOSE: Auricular acupuncture at the relaxation point has been shown to be
      effective treatment for anxiety. We hypothesized that auricular acupressure may
      decrease anxiety in elderly individuals who are transported by ambulance before
      receiving ESWL. MATERIALS AND METHODS: We enrolled 100 patients with renal
      calculi who were transported to the local hospital by special ambulance,
      accompanied by 2 paramedics. Paramedic 1 performed data collection, while
      paramedic 2 performed auricular acupressure in patients randomly assigned to a
      relaxation group and a sham treated group. Anxiety was measured using a visual
      analog scale score on a scale of 0 to 100 mm. RESULTS: Each group consisted of 50
      patients with similar demographic characteristics. The relaxation group had
      significantly decreased anxiety scores upon arrival at the hospital and lower
      anticipation of pain scores (mean+/-SD 57.6+/-21.8 to 15.4+/-9.8 and 35.7+/-29.7
      to 9.5+/-4.1 mm VAS) than the sham treated group (55.5+/-25.9 to 49.8+/-28.9 and
      37.7+/-24.1 to 33.8+/-25.2 mm VAS, respectively, 2-way repeated measure ANOVA
      each p=0.001). Estimated waiting times for treatment did not differ significantly
      between the 2 groups (5.0+/-2.5 and 5.5+/-2.95, respectively, repeated measures
      ANOVA p=0.83). The Post-Intervention Anxiety visual analog scale demonstrated the
      significant superiority of the true treatment group (19.5+/-5.9 and 66.8+/-27.9
      mm VAS, respectively, p=0.001). CONCLUSIONS: Elderly patients who received
      auricular acupressure at specific relaxation points while being transported to
      the hospital were less anxious, anticipated less pain and were more optimistic
      about the outcome of treatment that they will receive than the sham treated
      group. These data prove that this is an effective treatment for anxiety that
      improves the patient overall perception of ESWL.

PMID- 17499305
TI  - Effect of comestibles on symptoms of interstitial cystitis.
AB  - PURPOSE: Anecdotal evidence suggests that patients with painful bladder
      syndrome/interstitial cystitis report symptom exacerbation after consuming
      particular foods, beverages and/or supplements. We determined the prevalence of
      the effect of comestibles on painful bladder syndrome/interstitial cystitis
      symptoms and identified particular comestible items more likely to affect such
      symptoms. MATERIALS AND METHODS: A validated questionnaire designed to detect
      whether food, beverages and/or supplements have an effect on bladder symptoms was
      administered to 104 patients meeting National Institute for Diabetes and
      Digestive and Kidney Diseases criteria for interstitial cystitis. In addition to
      answering general questions about the effect of comestibles on painful bladder
      syndrome/interstitial cystitis symptoms, subjects were asked to indicate whether
      each of 175 individual items worsened, improved or had no effect on symptoms.
      Each response was numerically scored on a scale of -2 to 2 and mean values were
      generated for each comestible item. RESULTS: Of the surveyed patients with
      painful bladder syndrome/interstitial cystitis 90.2% indicated that the
      consumption of certain foods or beverages caused symptom exacerbation. There was
      no correlation between allergies and the effect of comestibles on symptoms.
      Patients who reported that specific foods worsened symptoms tended to have higher
      O'Leary-Sant interstitial cystitis symptom index and problem index, and/or pelvic
      pain and urgency/frequency patient symptom scale scores. A total of 35 comestible
      items had a mean score of lower than -1.0, including caffeinated, carbonated and
      alcoholic beverages, certain fruits and juices, artificial sweeteners and spicy
      foods. CONCLUSIONS: There is a large cohort of patients with painful bladder
      syndrome/interstitial cystitis in whom symptoms are exacerbated by the ingestion
      of specific comestibles. The most frequently reported and most bothersome
      comestibles were coffee, tea, soda, alcoholic beverages, citrus fruits and
      juices, artificial sweeteners and hot pepper.

PMID- 17499306
TI  - Standard versus limited pelvic lymph node dissection for prostate cancer in
      patients with a predicted probability of nodal metastasis greater than 1%.
AB  - PURPOSE: We determined the yield of standard vs limited pelvic lymphadenectomy in
      patients with a predicted risk of lymph node metastasis greater than 1% according
      to the Partin tables predicted probability of pathological stage. We also
      determined the feasibility of laparoscopic standard pelvic lymph node dissection.
      MATERIALS AND METHODS: Of 1,269 patients with clinically localized prostate
      cancer undergoing radical prostatectomy, 648 had a Partin's table predicted
      probability of lymph node invasion greater than 1%. Of the 648 patients 177
      underwent limited pelvic lymph node dissection performed laparoscopically (group
      1), and 471 underwent standard pelvic lymph node dissection performed open (367)
      or laparoscopically (104) (group 2). Templates of limited pelvic lymph node
      dissection included the external iliac lymph nodes whereas standard pelvic lymph
      node dissection included the external iliac, obturator and hypogastric lymph
      nodes. Multivariate logistic regression analyses were performed to compare the
      node positivity rate between groups 1 and 2. RESULTS: On multivariate logistic
      regression analysis controlling for prostate specific antigen, biopsy Gleason
      sum, clinical stage and surgical approach, the odds of node positivity were 7.15
      fold higher (95% CI 2.49-20.5, p<0.001) for standard vs limited pelvic lymph node
      dissection. The median (mean) number of nodes retrieved was 9 (10) and 14 (15)
      after limited and standard pelvic lymph node dissection, respectively (p<0.001).
      A similar impact was observed in patients treated laparoscopically with standard
      vs limited pelvic lymph node dissection (odds ratio 15.6, 95% CI 3.7-66.4,
      p<0.001). CONCLUSIONS: Standard lymph node dissection yields positive nodes more
      frequently and retrieves a higher total nodal count than the often performed
      pelvic lymph node dissection limited to the external iliac nodes. Standard pelvic
      lymph node dissection is feasible through a transperitoneal laparoscopic
      approach.

PMID- 17499308
TI  - Under diagnosis and over diagnosis of prostate cancer.
AB  - PURPOSE: We quantified the rates of over and under diagnosis of prostate cancer
      in 2 large patient cohorts during the last 15 years. MATERIALS AND METHODS: A
      total of 2,126 men with clinical stage T1c prostate cancer were treated with
      radical prostatectomy during 1 of the 3 periods 1989 to 1995, 1995 to 2001 and
      2001 to 2005. The respective proportions of men with a tumor that met our
      criteria for over diagnosis (0.5 cm3 or less, confined to the prostate with clear
      surgical margins and no Gleason pattern 4 or 5) and under diagnosis (nonorgan
      confined, pathological stage T3 or greater, or positive surgical margins) were
      examined. RESULTS: The proportion of men with an over diagnosed tumor was 1.3% to
      7.1%. The proportion with prostate cancer that was under diagnosed was 25% to
      30%. An ancillary finding was that decreasing the prostate specific antigen
      threshold for biopsy from 4.0 to 2.5 ng/ml in the screened population resulted in
      a lower rate of under diagnosis from 30% to 26%, a higher rate of over diagnosis
      from 1.3% to 7.1% and an increase in the 5-year progression-free survival rate
      from 85% to 92%. Men who were 55 years or younger were significantly more likely
      to meet our criteria for over diagnosed cancer. CONCLUSIONS: Under diagnosis of
      prostate cancer continues to occur more frequently than over diagnosis. Lowering
      the prostate specific antigen threshold for recommending biopsy to 2.5 ng/ml
      resulted in a lower rate of under diagnosis and a higher progression-free
      survival rate.

PMID- 17499310
TI  - Enhancement of gastric mucosal integrity by Lactobacillus rhamnosus GG.
AB  - The gastric mucosa is frequently exposed to different exogenous and endogenous
      ulcerative agents. Alcoholism is one of the risk factors for the development of
      mucosal damage in the stomach. This study aimed to assess if a probiotic strain
      Lactobacillus rhamnosus GG (LGG) is capable of protecting the gastric mucosa from
      acute damage induced by intragastric administration of ethanol. Pre-treatment of
      rats with LGG at 10(9) cfu/ml twice daily for three consecutive days markedly
      reduced ethanol-induced mucosal lesion area by 45%. LGG pre-treatment also
      significantly increased the basal mucosal prostaglandin E(2) (PGE(2)) level. In
      addition, LGG attenuated the suppressive actions of ethanol on mucus-secreting
      layer and transmucosal resistance and reduced cellular apoptosis in the gastric
      mucosa. It is suggested that the protective action of LGG on ethanol-induced
      gastric mucosal lesions is likely attributed to the up-regulation of PGE(2),
      which could stimulate the mucus secretion and increase the transmucosal
      resistance in the gastric mucosa. All these would protect mucosal cells from
      apoptosis in the stomach.

PMID- 17499311
TI  - Down-regulation of mitofusin-2 expression in cardiac hypertrophy in vitro and in
      vivo.
AB  - Mitofusin-2 (Mfn2) suppresses smooth muscle cell proliferation through inhibition
      of the Ras-extracellular signal-regulated kinases (ERK1/2) pathway. Since the
      ERK1/2 pathway is implicated in mediating hypertrophic signaling, we studied the
      changes in Mfn2 in cardiac hypertrophy using in vitro and in vivo models.
      Phenylephrine was used to induce hypertrophy in neonatal rat ventricular myocytes
      (NRVMs). In vivo hypertrophy models included spontaneously hypertensive rats
      (SHR), pressure-overload hypertrophy by transverse aortic constriction (TAC),
      hypertrophy of non-infarcted myocardium following myocardial infarction (MI), and
      cardiomyopathy due to cardiac-restricted overexpression of beta(2)-adrenergic
      receptors (beta(2)-TG). We determined hypertrophic parameters and analysed
      expression of atrial natriuretic peptide (ANP) and Mfn2 by real-time PCR.
      Phosphorylated-ERK1/2 (phospho-ERK) was measured by Western blot. Mfn2 was
      downregulated in phenylephrine treated NRCMs (by approximately 40%),
      hypertrophied hearts from SHR (by approximately 80%), mice with TAC (at 1 and 3
      weeks, by approximately 50%), and beta(2)-TG mice (by approximately 20%).
      However, Mfn2 was not downregulated in hypertrophied hearts with 15 weeks of TAC,
      nor in hypertrophied non-infarcted myocardium following MI. phospho-ERK1/2 was
      increased in hypertrophied myocardium at 1 week post-TAC, but not in non
      infarcted myocardium after MI, indicating that downregulated Mfn2 may be
      accompanied by an increase of phospho-ERK1/2. This study shows, for the first
      time, downregulated Mfn2 expression in hypertrophied hearts, which depends on the
      etiology and time course of hypertrophy. Further study is required to examine the
      causal relationship between Mfn2 and cardiac hypertrophy.

PMID- 17499312
TI  - The potentiation of curcumin on insulin-like growth factor-1 action in MCF-7
      human breast carcinoma cells.
AB  - Curcumin has anticarcinogenic and chemopreventive properties in a variety of
      experimental cancer models. Our in vitro studies have shown that curcumin
      inhibits cell growth and induces apoptosis in MCF-7, a human breast carcinoma
      cell line. The insulin-like growth factor-1 (IGF-1) system, including IGFs (IGF-1
      and IGF-2), IGF-1R (IGF-1 receptor) and IGFBPs (IGF binding proteins), has been
      implicated to play a critical role in the development of breast cancer. The aim
      of the present study was to investigate whether the growth inhibitory effects of
      curcumin were related to changes of the IGF-1 system in MCF-7 cells. IGF-1 at 50
      microg/l in serum-free medium produced maximum proliferation and minimized
      apoptosis. However, curcumin exhibited a potent ability to blunt IGF-1-stimulated
      MCF-7 cell growth and reverse the IGF-1-induced apoptosis resistance. To
      determine whether curcumin intervenes in IGF-1 or IGFBP-3 secretion, MCF-7 cells
      were incubated in serum-free medium in the presence of various concentrations of
      curcumin for indicated time periods. Curcumin decreased the secretion of IGF-1
      with a concomitant increase of IGFBP-3 in a dose-dependent manner. Receptor
      tyrosine kinase assays revealed that IGF-1-stimulated IGF-1R tyrosine kinase
      activation was also abrogated by curcumin in a dose-dependent manner. Real-time
      fluorescence quantitative reverse transcriptase-polymerase chain reaction (RFQ-RT
      PCR) further revealed that curcumin suppressed IGF-1R gene expression at
      transcriptional level. In conclusion, the inhibition of cell growth and induction
      of apoptosis by curcumin in MCF-7 cells might be mediated, at least partially, by
      its ability to down-regulate the IGF-1 axis.

PMID- 17499313
TI  - Cholinergic modulation of anaphylactic shock: plasma proteins influence.
AB  - Cholinergic drugs can modulate anaphylactic shock and change lymphocyte
      functions. Plasma proteins modulate effects of muscarinic antagonists during
      anaphylactic shock. The present investigation was carried out to study the
      antianaphylactic activity of methacine (antagonist at muscarinic receptors) in
      combination with neostigmine (anticholinesterase drug). However, it is not known
      whether plasma proteins-albumin, C-reactive protein (CRP) and immunoglobulin G
      (IgG) - modify the effects of cholinergic drugs like methacine, serotonin (5-HT)
      level in the lymphoid organs and quantity of antibody-forming cells (AFC) in the
      spleen of guinea pigs during experimental anaphylactic shock. It was shown that
      administration of methacine with neostigmine (40 min and 15 min prior to shock
      induction, accordingly) at the pathochemical stage revokes shock development. By
      blocking cholinesterase endogenous acetylcholine is increased and methacine
      blocks muscarinic receptors and therewith unwanted side effects in the airways
      (bronchoconstriction) and heart (bradycardia). Administration of the combination
      of methacine with neostigmine at the immunological stage (guinea pig
      sensitization) does not affect the course of anaphylactic shock. Administration
      of methacine with IgG at the pathochemical stage of shock significantly decreases
      shock intensity, while administration of methacine with CRP or albumin has no
      influence on the shock. Administration of IgG or CRP (not albumin) at the
      immunological stage of shock and albumin or IgG (not CRP) at the pathochemical
      stage leads to reduction of the anaphylactic reaction. Application of methacine
      with neostigmine or IgG (effective combinations of drugs) results in
      normalization of antibody response in the spleen and 5-HT level in the lymphoid
      organs. Administration of methacine with CRP or albumin (ineffective combinations
      of drugs) leads to increase of antibody response in the spleen and 5-HT level in
      the lymphoid organs. Administration of hexamethonium or aceclidine aggravated
      anaphylactic shock reaction. Thus, the combination of methacine with neostigmine
      can regulate the pathochemical stage of shock and the 5-HT release. At the
      pathochemical stage of shock IgG increases the antianaphylactic activity of
      methacine, but albumin and CRP abolish it.

PMID- 17499314
TI  - Effect of tubular inhomogeneities on filter properties of thick ascending limb of
      Henle's loop.
AB  - We used a simple mathematical model of rat thick ascending limb (TAL) of the loop
      of Henle to predict the impact of spatially inhomogeneous NaCl permeability,
      spatially inhomogeneous NaCl active transport, and spatially inhomogeneous
      tubular radius on luminal NaCl concentration when sustained, sinusoidal
      perturbations were superimposed on steady-state TAL flow. A mathematical model
      previously devised by us that used homogeneous TAL transport and fixed TAL radius
      predicted that such perturbations result in TAL luminal fluid NaCl concentration
      profiles that are standing waves. That study also predicted that nodes in NaCl
      concentration occur at the end of the TAL when the tubular fluid transit time
      equals the period of a periodic perturbation, and that, for non-nodal periods,
      sinusoidal perturbations generate non-sinusoidal oscillations (and thus a series
      of harmonics) in NaCl concentration at the TAL end. In the present study we find
      that the inhomogeneities transform the standing waves and their associated nodes
      into approximate standing waves and approximate nodes. The impact of
      inhomogeneous NaCl permeability is small. However, for inhomogeneous active
      transport or inhomogeneous radius, the oscillations for non-nodal periods tend to
      be less sinusoidal and more distorted than in the homogeneous case and to thus
      have stronger harmonics. Both the homogeneous and non-homogeneous cases predict
      that the TAL, in its transduction of flow oscillations into concentration
      oscillations, acts as a low-pass filter, but the inhomogeneities result in a less
      effective filter that has accentuated non-linearities.

PMID- 17499315
TI  - [Intracranial aneurysm associated with aortic coarctation: a case report and
      literature review].
AB  - We report a new and rare case associating an intracranial aneurysm and aortic
      coarctation. Based on this case and a review of the literature we discuss the
      clinical aspects, the pathogenesis and the management of this disorder
      predominantly observed in the adolescent and young adult population.

PMID- 17499316
TI  - Individual differences in interhemispheric transfer time (IHTT) as measured by
      event related potentials.
AB  - The present study examined possible gender differences in interhemisperic
      transfer time (IHTT), as measured by event related potentials (ERPs). Using
      visual half-field presentations of letter pairs in a match/no-match paradigm, N1
      latency was measured for each visual half-field and hemisphere. IHTTs were
      determined by subtracting the "direct" (i.e., contralateral or non-callosal)
      pathway N1 latency from the "indirect" (i.e., callosal) pathway N1 latency. Based
      on studies showing gender differences in corpus callosum size and function, we
      hypothesized that females would show more symmetric and faster overall transfer
      times than males. Results showed faster right-to-left IHTT across all
      participants, but females had more symmetric IHTT and shorter overall IHTT-
      primarily due to significantly shorter left-to-right times compared to males.
      Little support was found for the influence of hemisphere (i.e., "direct" pathway)
      response, or potential lateralization of function, on the length of IHTT in
      either direction.

PMID- 17499317
TI  - Lesion correlates of conversational speech production deficits.
AB  - We assess brain areas involved in speech production using a recently developed
      lesion-symptom mapping method (voxel-based lesion-symptom mapping, VLSM) with 50
      aphasic patients with left-hemisphere lesions. Conversational speech was
      collected through a standardized biographical interview, and used to determine
      mean length of utterance in morphemes (MLU), type token ratio (TTR) and overall
      tokens spoken for each patient. These metrics are used as indicators of
      grammatical complexity, semantic variation, and amount of speech, respectively.
      VLSM analysis revealed that damage to the anterior insula was predictive of low
      scores on MLU and tokens, consistent with prior findings of the role of this
      region in speech production [Dronkers, N. F. (1996). A new brain region for
      coordinating speech articulation. Nature, 384(6605), 159-161]. Additionally, the
      inferior frontal gyrus, sensorimotor and anterior temporal areas were also
      associated with lower scores on both of these measures. Overall, token and MLU
      maps were highly similar, suggesting an overlap between grammatical language
      networks and overall fluency. TTR maps also shared some portions of this network,
      but damage to posterior temporal regions also reduced scores on this measure.
      These results represent the first voxel-based lesion analysis of speech
      production performance in aphasic patients.

PMID- 17499318
TI  - Goal-dependent modulation of declarative memory: neural correlates of temporal
      recency decisions and novelty detection.
AB  - Declarative memory allows an organism to discriminate between previously
      encountered and novel items, and to place past encounters in time. Numerous
      imaging studies have investigated the neural processes supporting item
      recognition, whereas few have examined retrieval of temporal information. In the
      present study, functional magnetic resonance imaging (fMRI) was conducted while
      subjects engaged in temporal recency and item novelty decisions. Subjects
      encountered three-alternative forced-choice retrieval trials, each consisting of
      two words from a preceding study phase and one novel word, and were instructed to
      either identify the novel item (Novelty trials) or the more recently presented
      study item (Recency trials). Relative to correct Novelty decisions, correct
      Recency decisions elicited greater activation in a network of left-lateralized
      regions, including frontopolar and dorsolateral prefrontal cortex and
      intraparietal sulcus. A conjunction analysis revealed that these left-lateralized
      regions overlapped with those previously observed to be engaged during source
      recollection versus novelty detection, suggesting that during Recency trials
      subjects attempted to recollect event details. Consistent with this
      interpretation, correct Recency decisions activated posterior hippocampus and
      parahippocampal cortex, whereas incorrect Recency decisions elicited greater
      anterior cingulate activation. The magnitude of this latter effect positively
      correlated with activation in right dorsolateral prefrontal cortex. Finally,
      correct Novelty decisions activated the anterior medial temporal lobe to a
      greater extent than did correct Recency decisions, suggesting that medial
      temporal novelty responses are not obligatory but rather can be modulated by the
      goal-directed allocation of attention. Collectively, these findings advance
      understanding of how subjects strategically engage frontal and parietal
      mechanisms in the service of attempting to remember the temporal order of events,
      and how retrieval goals impact novelty processing within the medial temporal
      lobe.

PMID- 17499319
TI  - Ethnic differences in the occurrence of oropharyngeal cancer in Taiwan.
AB  - OBJECTIVE: The purpose of this study was to examine the oropharyngeal cancer
      pattern among different ethnic groups in Taiwan. METHODS: The sample population
      was divided into three ethnic groups: the Fukkien, Hakka, and aboriginal
      communities. Age-standardized mortality rates (SMRs) and age-standardized
      incidence rates (SIRs) were estimated among these ethnic groups for the period
      1979-1996/1997. RESULTS: Our study found that the higher oropharyngeal cancer
      mortality and incidence rates in females of aboriginal groups are statistically
      significant, and higher than reference groups for both genders (SMR=3.76,
      SIR=2.18). However, in the lower areca quid chewing aboriginal groups, the higher
      pattern was not seen in females, and the lower pattern was even found in males.
      The incidence and mortality rate of oropharyngeal cancer in Hakkas was
      significantly lower than in the reference group. CONCLUSIONS: The pattern of
      oropharyngeal cancer in Taiwan showed ethnic differences. The differences may be
      due to variation in exposure to different risk factors; however, in our study, we
      found that genetic differences might also be considered when explaining the
      different oropharyngeal cancer patterns among ethnic groups.

PMID- 17499320
TI  - Socio-economic inequalities in health and service utilization in the London
      Borough of Newham.
AB  - OBJECTIVES: To examine the extent of socio-economic inequalities in health in the
      London Borough of Newham and to compare them with those in the UK as a whole.
      STUDY DESIGN: Cross-sectional, individual-level observational study with data on
      socio-economic and health measures from wave one of the Newham Household Panel
      Survey (n=1723) and wave 11 of the British Household Panel Survey (n=8444).
      METHODS: Age-standardized comparison of the social distribution, by household
      social class, education, housing conditions and neighbourhood problems, of six
      indicators of health and service utilization. Relative index of inequality is
      used to compare magnitude of inequality across the samples. RESULTS: Age
      standardized prevalence ratios for most health and service use indicators
      indicated that Newham has poorer health and higher utilization compared with the
      UK as a whole. Significant health inequalities were associated with socio
      economic measures in both Newham and Britain, but few significant differences in
      the relative effects between the two. CONCLUSIONS: Although Newham has higher
      prevalence of poor health and high service use, the relative effects of socio
      economic inequalities are similar to those in Britain as a whole.

PMID- 17499321
TI  - Melioidosis in a rural community of Western Province, Papua New Guinea.
AB  - A prospective study was conducted to determine the significance of melioidosis in
      the Balimo district of Western Province, Papua New Guinea. During 1998, after the
      establishment of laboratory procedures and increasing local clinical awareness,
      the disease was found in 1.8% (95% CI 0.37-5.1%) of individuals presenting with
      fever refractory to standard treatment. The clinical incidence was 20.0 per
      100,000 population (95% CI 12.2-30.9). The median age of culture-confirmed cases
      was 9.5 years (interquartile range 8.3-14.8 years). The seroprevalence of 747
      community children in the region tested was 8.2% (95% CI 6.2-10.4%). Most
      individuals presented during the rainy season with a febrile disease refractory
      to standard treatment, sometimes mimicking tuberculosis. Some family clustering
      was apparent. All patients with bacteraemic melioidosis died, but treatment with
      the available conventional therapies of chloramphenicol, co-trimoxazole or
      doxycycline resulted in survival and cure in six patients with subacute/localised
      melioidosis. Further studies are needed to ascertain the local epidemiology and
      why children appear particularly at risk, as well as to establish the true extent
      of melioidosis in Papua New Guinea.

PMID- 17499322
TI  - Recent advances in oxasteroids chemistry.
AB  - The continuous interest in the field of oxasteroids mainly arises from the
      fascinating aspects associated with their peculiar stereochemical features and
      their promising and sometimes unexpected biological activities. The recent
      development in the partial and total syntheses of oxasteroids are herein
      described.

PMID- 17499323
TI  - Spatiotemporal population distributions and their implications for species
      coexistence in a variable environment.
AB  - A population experiences environmental variation both directly, through effects
      on life history parameters such as fecundity, and indirectly, through effects on
      the population distributions of competitors and thus on the distribution of
      competition. Which spatial and temporal scales of environmental variation most
      influence the coexistence of two species thus depends in part on the degree to
      which the resident population responds to different scales of variation. In this
      paper, I calculate an approximation for a spatiotemporal population distribution
      as the result of a filter function convolved with the environmental variation. I
      find that there is no straightforward connection between spatial or temporal
      scales inherent to an organism's life history, such as mean lifetime or dispersal
      distance, and the population's sensitivity to variation at different scales.
      Rather, life history traits interact sensitively with the way environmental
      variation affects the organism. I comment on the implications for variation
      mediated coexistence.

PMID- 17499324
TI  - Research toward the development of a biologically based dose response assessment
      for inorganic arsenic carcinogenicity: a progress report.
AB  - Cancer risk assessments for inorganic arsenic have been based on human
      epidemiological data, assuming a linear dose response below the range of
      observation of tumors. Part of the reason for the continued use of the linear
      approach in arsenic risk assessments is the lack of an adequate biologically
      based dose response (BBDR) model that could provide a quantitative basis for an
      alternative nonlinear approach. This paper describes elements of an ongoing
      collaborative research effort between the CIIT Centers for Health Research, the
      U.S. Environmental Protection Agency, ENVIRON International, and EPRI to develop
      BBDR modeling approaches that could be used to inform a nonlinear cancer dose
      response assessment for inorganic arsenic. These efforts are focused on: (1) the
      refinement of physiologically based pharmacokinetic (PBPK) models of the kinetics
      of inorganic arsenic and its metabolites in the mouse and human; (2) the
      investigation of mathematical solutions for multi-stage cancer models involving
      multiple pathways of cell transformation; (3) the review and evaluation of the
      literature on the dose response for the genomic effects of arsenic; and (4) the
      collection of data on the dose response for genomic changes in the urinary
      bladder (a human target tissue for arsenic carcinogenesis) associated with in
      vivo drinking water exposures in the mouse as well as in vitro exposures of both
      mouse and human cells. An approach is proposed for conducting a biologically
      based margin of exposure risk assessment for inorganic arsenic using the in vitro
      dose response for the expression of genes associated with the obligatory
      precursor events for arsenic tumorigenesis.

PMID- 17499325
TI  - A comparison of the mouse bioassay with liquid chromatography-mass spectrometry
      for the detection of lipophilic toxins in shellfish from Scottish waters.
AB  - Some lipophilic shellfish toxins (LSTs) can cause human illness due to eating
      shellfish that have become naturally contaminated following filter feeding on
      toxin producing algae. A mouse bioassay (MBA) is widely used to detect LSTs in
      regulatory monitoring of shellfish. However, the MBA is imprecise giving only a
      positive or negative result and is prone to interference from other compounds. In
      this study, liquid chromatography-mass spectrometry (LC-MS) was compared to the
      MBA, with the aim of substituting the in vivo assay for monitoring shellfish from
      Scottish waters. Overall, it was not feasible to demonstrate equivalence of LC-MS
      with the MBA, but due to the detection of a range of LSTs, it is considered that
      LC-MS methods capable of detecting multiple analogues are accepted by
      international markets of shellfish to assure consumer protection.

PMID- 17499326
TI  - Recombinant modified vaccinia virus Ankara provides durable protection against
      disease caused by an immunodeficiency virus as well as long-term immunity to an
      orthopoxvirus in a non-human primate.
AB  - Recombinant and non-recombinant modified vaccinia virus Ankara (MVA) strains are
      currently in clinical trials as human immunodeficiency virus-1 (HIV) and
      attenuated smallpox vaccines, respectively. Here we tested the ability of a
      recombinant MVA delivered by alternative needle-free routes (intramuscular,
      intradermal, or into the palatine tonsil) to protect against immunodeficiency and
      orthopoxvirus diseases in a non-human primate model. Rhesus macaques were
      immunized twice 1 month apart with MVA expressing 5 genes from a pathogenic
      simian human immunodeficiency virus (SHIV)/89.6P and challenged intrarectally 9
      months later with the pathogenic SHIV/89.6P and intravenously 2.7 years later
      with monkeypox virus. Irrespective of the route of vaccine delivery, binding and
      neutralizing antibodies and CD8 responses to SHIV and orthopoxvirus proteins were
      induced and the monkeys were successively protected against the diseases caused
      by the challenge viruses in unimmunized controls as determined by viral loads and
      clinical signs. These non-human primate studies support the clinical testing of
      recombinant MVA as an HIV vaccine and further demonstrate that MVA can provide
      long-term poxvirus immunity, essential for use as an alternative smallpox
      vaccine.

PMID- 17499327
TI  - Coat protein-mediated resistance to TMV infection of Nicotiana tabacum involves
      multiple modes of interference by coat protein.
AB  - Expression of tobacco mosaic virus (TMV) coat protein (CP) restricts virus
      disassembly and alters the accumulation of the movement protein (MP). To
      characterize the role of structure of transgenic CP in regulating virus
      disassembly and production of MP, we generated CPs with mutations at residues
      Glu50 and Asp77, located in the interface between juxtaposed CP subunits. In
      transgenic Nicotiana tabacum and BY-2 cells, three categories of coat protein
      mediated resistance (CP-MR) levels were identified: wild-type CP-MR; elevated CP
      MR; and no CP-MR. Mutant CPs that interfered with the accumulation of virus
      replication complexes conferred very high levels of protection to TMV, except by
      CP(E50D) which provided no protection in the systemic host (Xanthi-nn) but high
      CP-MR in the local lesion host (Xanthi-NN). In transgenic BY-2 cells CP(E50D)
      strongly reduced accumulation of MP:GFP. In general, there was a strong
      correlation between the capacity for CP to assemble to pseudovirions and CP-MR,
      while there was not strong correlation with packaging viral RNA and CP-MR. The
      data demonstrate that interference with one or more steps in virus infection and
      replication by wild type and mutant CP determine the degree of CP-MR.

PMID- 17499328
TI  - HIV-1 prophylactic vaccine comprised of topical DermaVir prime and protein boost
      elicits cellular immune responses and controls pathogenic R5 SHIV162P3.
AB  - Topical DNA vaccination (DermaVir) facilitates antigen presentation to naive T
      cells. DermaVir immunization in mice, using HIV-1 Env and Gag, elicited cellular
      immune responses. Boosting with HIV-1 gp120 Env and p41 Gag augmented Th1
      cytokine levels. Intramuscular DNA administration was less efficient in priming
      antigen-specific cytokine production and memory T cells. In rhesus macaques,
      DermaVir immunization induced Gag- and Env-specific Th1 and Th2 cytokines and
      generation of memory T cells. Boosting of DermaVir-primed serum antibody levels
      was noted following gp140(SHIV89.6P)/p27(SIV) immunization. Rectal challenge with
      pathogenic R5-tropic SHIV162P3 resulted in control of plasma viremia (4/5
      animals) that was reflected in jejunum, colon and mesenteric lymph nodes. An
      inverse correlation was found between Gag- and Env-specific central memory T cell
      responses on the day of challenge and plasma viremia at set point. Overall, the
      topical DermaVir/protein vaccination yields central memory T cell responses and
      facilitates control of pathogenic SHIV infection.

PMID- 17499329
TI  - Cyanophage Pf-WMP4, a T7-like phage infecting the freshwater cyanobacterium
      Phormidium foveolarum: complete genome sequence and DNA translocation.
AB  - We report the complete 40,938-bp genome sequence of a cyanophage, Pf-WMP4, which
      infects the freshwater cyanobacterium Phormidium foveolarum Gom. Nine of the
      forty-five potential open reading frames in the Pf-WMP4 genome share similarities
      with the genes found in T7-like phages. Using in vitro transcription, we found
      that seven promoters at the leftmost end of the genome can be recognized by the
      host RNA polymerase. By blocking transcriptional and translational inhibitors, we
      found that Pf-WMP4 DNA translocation, with an average translocation rate of
      19.8+/-2.7 bp s(-1) at 28 degrees C, requires both host transcription and protein
      synthesis of an unknown factor. Therefore the mechanism of cyanophage Pf-WMP4 DNA
      injection may be driven both by a T7-like internalization mechanism as well as an
      additional unknown mechanism requiring de novo protein synthesis. Our analysis of
      the Pf-WMP4 genome sheds new light on the translocation strategies and
      evolutionary traces of phages belonging to the T7 supergroup.

PMID- 17499331
TI  - Interaction of rotavirus with human peripheral blood mononuclear cells:
      plasmacytoid dendritic cells play a role in stimulating memory rotavirus specific
      T cells in vitro.
AB  - We studied the interaction of RV with human peripheral blood mononuclear cells
      (PBMC) from adult volunteers. After exposure of PBMC to rhesus RV (RRV), T and B
      lymphocytes, NK cells, monocytes, and myeloid and plasmacytoid dendritic cells
      expressed RV non-structural proteins, at variable levels. Expression of these RV
      proteins was abolished if infection was done in the presence of anti-VP7
      neutralizing antibodies or 10% autologous serum. Supernatants of RRV exposed PBMC
      contained TNF-alpha, IL-6, IFN-alpha, IFN-gamma, IL-2 and IL-10. Plasmacytoid DC
      were found to be the main source of IFN-alpha production, and in their absence
      the production of IFN-gamma and the frequency of RV specific T cells that secrete
      IFN-gamma diminished. Finally, we could not detect RV-antigen associated with the
      PBMC or expression of RV non-structural proteins in PBMC of acutely RV-infected
      children. Thus, although PBMC are susceptible to the initial steps of RV
      infection, most PBMC of children with RV-gastroenteritis are not infected.

PMID- 17499330
TI  - Vaccinia virus temperature-sensitive mutants in the A28 gene produce non
      infectious virions that bind to cells but are defective in entry.
AB  - The vaccinia virus temperature-sensitive mutations Cts6 and Cts9 were mapped by
      marker rescue and DNA sequencing to the A28 gene. Cts6 and Cts9 contain an
      identical 2-bp deletion truncating the A28 protein and removing the fourth
      conserved cysteine near the C-terminus. Cts9 mutant virions produced at 40
      degrees C were non-infectious and unable to cause cytopathic effect. However, the
      mutant A28 protein localized to purified mature virions (MV) at 31 degrees C and
      40 degrees C. MV of Cts9 produced at 40 degrees C bound to cells but did not
      enter cells. Low pH treatment of Cts9-infected cells at 18 h p.i. failed to
      produce fusion from within at 40 degrees C, but gave fusion at 31 degrees C.
      Adsorption of Cts9 mutant virions to cells followed by low pH treatment showed a
      defect in fusion from without. The Cts9 phenotype suggests that the A28 protein
      is involved in both virus entry and cell-cell fusion, and supports the linkage
      between the two processes.

PMID- 17499332
TI  - Perceptual completion in a dynamic scene: an investigation with an ambiguous
      motion paradigm.
AB  - In this study we employed the streaming-bouncing stimulus to investigate aspects
      of dynamic occlusion, e.g., of objects that temporarily move under occlusion
      while covertly being tracked. Two occluders, both either luminance-defined or
      invisible (virtual), were placed on the trajectories of the moving objects in the
      streaming-bouncing stimulus. We found that the bouncing percept was dominant when
      the objects moved under luminance-defined occluders but not when they moved under
      virtual occluders. Perceived motion direction thus varied with occluder
      visibility. The results seem to suggest that perceptual completion of a moving
      object interferes with constant motion processing of the same object.

PMID- 17499333
TI  - Chromatic tuning of contour-shape mechanisms revealed through the shape-frequency
      and shape-amplitude after-effects.
AB  - We investigated whether contour-shape processing mechanisms are selective for
      color direction using the shape-frequency and shape-amplitude after-effects, or
      SFAE and SAAE [Gheorghiu, E. & Kingdom, F. A. A. (2006). Luminance-contrast
      properties of contour-shape processing revealed through the shape-frequency after
      effect. Vision Research, 46(21), 3603-3615. Gheorghiu, E. & Kingdom, F. A. A.
      (2007). The spatial feature underlying the shape-frequency and shape-amplitude
      after-effects. Vision Research, 47(6), 834-844]. All contours were defined along
      the 'red-green', 'blue-yellow' and 'luminance' axes of cardinal color space.
      Adapting and test contours were defined along the same or along opposite
      polarities within a cardinal axis, and along the same or along different cardinal
      axes. We found (i) little transfer of the after-effects across different within
      axis polarities, for all cardinal axes and for both even-symmetric and odd
      symmetric contours; (ii) little transfer between the red-green and blue-yellow
      cardinal axes; (iii) little transfer between the chromatic and luminance cardinal
      directions for the SAAE; (iv) large transfer between the chromatic and luminance
      cardinal directions for the SFAE. We conclude that contour-shape mechanisms are
      selective for within-cardinal axis polarity and for the chromatic axes within the
      isoluminant plane. However for certain types of contour-shape processing they are
      poorly selective along the chromatic versus luminance dimension. Overall our
      results suggest that contour-shape encoding mechanisms are selective for color
      direction and that color is important for contour-shape processing.

PMID- 17499334
TI  - The study on the dechlorination of OCDD with Pd/C catalyst in ethanol-water
      solution under mild conditions.
AB  - Dechlorination of octachlorodibenzo-p-dioxin (OCDD) was carried out in ethanol
      water (v/v=1:1) solution of NaOH in the presence of Pd/C catalysts with the use
      of H(2). The substrate was dechlorinated with Pd/C under mild conditions
      (atmospheric pressure and <100 degrees C) to give a chlorine-free product,
      dibenzo-p-dioxin (DD), in high yields. After reaction of 3h at 50 degrees C,
      95.9% OCDD was degraded to low dechlorinated congeners and the yield of DD was
      77.4%. We have also studied the dechlorination selectivity of chlorine atoms on
      the different substituted positions and postulated the dechlorination pathway of
      OCDD. For OCDD, the 2-position has higher reactivity than 1-position, but the
      difference is very small. From the distribution statistics of the intermediates
      during the reaction, we postulate that the steric effect plays an important role
      during the reaction and affect the dechlorination pathway of OCDD.

PMID- 17499335
TI  - "Solvent effects on the silylation-gas chromatography-mass spectrometric
      determination of natural and synthetic estrogenic steroid hormones" Comment on
      "Formation of chlorinated estrones via hypochlorous disinfection of wastewater
      effluent containing estrone" by Hideyuki Nakamura, Ryoko Kuruto-Niwa, Mitsuo
      Uchida and Yoshiyasu Terao [Chemosphere 66 (2007) 1441-1448].

PMID- 17499336
TI  - Application of nano-FIA-Direct-EI-MS to determine diethylene glycol in produced
      formation water discharges and seawater samples.
AB  - Diethylene glycol (DEG) is extensively used on offshore gas platforms to prevent
      the hydrate formation during the gas-water separation process and to inhibit
      corrosion events. This chemical might enter in the marine environment via the
      produced formation water (PFW) discharge. In this study, a new approach was
      applied to the investigation of the DEG content in PFW discharges and seawater
      samples from four gas installation platforms in the Adriatic Sea (Italy). The
      method includes an off-line solid-phase extraction/pre-concentration technique,
      followed by a nanoscale flow injection/direct-electron ionization (EI) mass
      spectrometric analysis. Direct-EI is a novel and miniaturized interface for
      directly coupling a liquid chromatograph with an electron ionization mass
      spectrometer. The capability to acquire EI spectra, and to operate in selected
      ion monitoring mode during actual sample analyses, allowed a precise
      quantification of DEG with a method limit of detection of 31microg/l. In
      addition, a careful evaluation of the matrix effect showed that, as opposed to
      electrospray ionization, the response of the Direct-EI interface was not affected
      by sample interferences.

PMID- 17499337
TI  - A summary of the 209 PCB congener nomenclature.
AB  - Primary publications of congener numbering shorthand systems for PCB congener
      identification were reviewed, including the original Ballschmiter-Zell (BZ)
      system; recommended changes by Schulte and Malisch, and Guitart et al.; and
      listings by the Chemical Abstracts Service. Comparisons of the various congener
      numbering shorthands and chlorine substitution numberings in the structural name
      listings are presented. Several changes, to adhere more closely to IUPAC rules,
      have been incorporated into the BZ structural nomenclature, and these resulted in
      renumbering congeners. These corrected listings have been erroneously identified
      as "IUPAC" numbers, a misnomer, because IUPAC has not published a shorthand
      system. Guitart pointed out additional inconsistencies with IUPAC rules for nine
      congeners which would result in further order changes, but did not recommend
      renumbering, to avoid further confusion. We noted an additional error in the
      structural name for congener 97, named 2,2',3',4,5 using Ballschmiter and Zell
      nomenclature and 2,2',3,4',5' using strict IUPAC nomenclature. This renaming
      would cause the renumbering of the IUPAC number system reported by Guitart for
      isomers 91 through 98. No further changes are recommended, however. Tables
      summarizing each publication, and the discrepancies between them are provided in
      hopes of clarifying the current state of the nomenclature.

PMID- 17499338
TI  - Anatomical pathology in the 21st century: the great paradigm shift.

PMID- 17499339
TI  - Lung involvement in childhood measles: severe immune dysfunction revealed by
      quantitative immunohistochemistry.
AB  - Measles, accounting for nearly 1 million deaths each year, presents intense
      involvement of lymphoid organs and the lungs. The immune response in situ in the
      lungs was determined in blocks recovered from 42 necropsies of children who died
      from measles determined by immune cell phenotype (CD4, CD8, CD20, CD45RO, CD68,
      natural killer [NK], and antigen S-100 B [S100]) and cytokine production
      (interferon, tumor necrosis factor, interleukin [IL]-1, IL-2, IL-4, IL-10, and IL
      12). Compared with the lungs of age-paired controls, patients with measles
      presented severe depletion of CD4+, CD20+, CD68+, NK+, and S100+ cells in
      alveolus- and bronchus-associated lymphoid tissue without depletion of CD8+
      cells. Most of these features were similar in both forms of measles lung
      involvement, Hecht giant cell, or interstitial pneumonia, but S100+ cells were
      depleted in bronchus-associated lymphoid tissue from patients with Hecht
      pneumonia, which also occurs more frequently in malnourished children. IL-10- and
      IL-12-producing cells were depleted in patients with measles, whereas IL-1-,
      interferon-, and IL-4-producing cells were more frequently seen in the alveolus
      of patients with measles compared with controls. Quantitative in situ immune cell
      phenotype and function in the lung in measles demonstrated severe immune
      dysfunction, with loss of key cells, such as dendritic, CD4+, and NK+ cells, and
      deficient cytokine production, which allows for a better comprehension of local
      reactions in this process.

PMID- 17499340
TI  - Preliminary findings of chemistry and bioaccessibility in base metal smelter
      slags.
AB  - Leaching of toxic metals from slag waste produced during smelting of Pb-Zn ores
      is generally considered to be negligible. A 1.4 million tonne stockpile of slag
      containing up to 2.5% Pb and other contaminants has accumulated on a smelter site
      at North Lake Macquarie, New South Wales, Australia, and it has also been freely
      used within the community for landscaping and drainage projects. It had been
      suggested that Pb in fine particles derived from the slags may be a potential
      contributor to the blood Pb of some children in this community, although there is
      conflicting evidence in the literature for such a hypothesis. Bioaccessibility of
      lead and selected metals derived from nine slag samples collected from areas of
      public open space was examined using a relatively simple in vitro gastric
      dissolution technique. Size analyses of the slag samples demonstrate that finely
      sized material was present in the slags which could be ingested, especially by
      children. The finer-sized particles contain high levels of Pb (6,490-41,400 ppm),
      along with Cd and As. Pb bioaccessibility of the slags was high, averaging 45%
      for -250 microm material and 75% for particles in the size range -53+32 microm.
      Increasing bioaccessibility and Pb concentration showed an inverse relationship
      to particle size. Almost 100% of Pb would be bioaccessible in the smallest slag
      particles (<20 microm), which also contained very high Pb levels ranging from
      50,000 to 80,000 ppm and thus constitute a potential health hazard for children.

PMID- 17499341
TI  - Comparative study of dark patinas on granitic outcrops and buildings.
AB  - Formation of dark patinas on rocky surfaces is mainly related to the deposition
      of gases and particles and to sulphation mechanisms. In the present study,
      samples of dark patinas taken from granitic outcrops and from granitic buildings
      were examined in an attempt to understand the mechanisms of their formation. The
      outcrops are located in non-polluted areas and are characterized by the absence
      of any extraneous material that provides calcium, such as e.g. mortar. The
      buildings are located in areas with low levels of pollution. The climate in the
      study area favours proliferation of microorganisms. Important differences between
      the patinas sampled from outcrops and from buildings were observed, as the former
      are of biological origin and the latter of anthropogenic origin. Although the
      levels of pollution are low in the sampling area, sulphur was present in all of
      the samples from urban buildings. Sulphur was not present in patinas from
      outcrops or in patinas from monuments that are assumed to behave as outcrops
      (dolmens), although the latter are also of anthropogenic origin. Finally, the
      patinas were found to be formed by elements accumulated on the surface and not
      from elements contained within the rock itself.

PMID- 17499342
TI  - Trace elements in soils and plants in temperate forest plantations subjected to
      single and multiple applications of mixed wood ash.
AB  - Wood ash, a by-product generated in power plants, can be used to fertilize forest
      plantations to replenish nutrients lost during harvesting. Although wood ash
      generally contains low levels of trace metals, release of some of these may occur
      soon after ash application in acid soils. The risk of heavy metal contamination
      associated with application of mixed wood ash was assessed in six Pinus radiata
      D. Don plantations, on two types of mineral soil differing in texture, drainage
      and CECe. Four of the stands received a single application of 4500 kg ha(-1)
      (March 2003), and in the other two stands the same treatment was applied over
      three consecutive years (2003-2005). Trace metal (Cd, Cr, Cu, Mn, Ni, Pb, Zn)
      concentrations were monitored throughout the 3 years in different components of
      the forest ecosystem--soil solid fraction, soil solution, tree needles, ground
      vegetation and different mushroom species. Repeated applications of wood ash led
      to moderate increases in soil extractable Mn and Zn, and Mn in all mushrooms
      species. However, the maximum concentrations did not reach levels potentially
      harmful to organisms. Concentrations of Zn, Cu and Cd decreased in some mushroom
      species, probably because of increased soil pH caused by the treatment. Heavy
      metal concentrations in tree needles and ground vegetation were not altered.
      Although the risk of heavy metal contamination appears to be low, the long-term
      effects of wood ash application must be assessed.

PMID- 17499343
TI  - Venous thromboembolism in carriers of the Factor V Leiden mutation and in
      patients without known thrombophilic risk factor; prediction of recurrence and
      APC-PCI complex concentration and/or soluble thrombomodulin antigen and activity.
AB  - BACKGROUND: The complex between activated protein C (APC) and the protein C
      inhibitor (PCI) is a sensitive indicator of the degree of activation of blood
      coagulation and higher concentrations have been measured in carriers of the FV
      Leiden mutation who were in the recovery phase after treatment for venous
      thromboembolism (VTE). OBJECTIVES: The main purpose of this study was to
      correlate the APC-PCI complex concentration to thrombomodulin activity and
      antigen concentration in the same group of patients. We also add a prospective
      clinical follow-up of the VTE recurrence after 1 year to investigate if the
      markers can predict the risk for a new VTE. PATIENTS/METHODS: Blood samples were
      collected from 50 patients with the FV Leiden mutation and 132 without any known
      risk factor for thrombophilia after finished treatment. RESULTS: The APC-PCI
      complex, s-TM activity and the quotient (s-TM activity)/(s-TM antigen) were
      higher in VTE patients with FV Leiden. In total, there were 19 VTE recurrences
      (10%) after 1 year. The OR for recurrence was 1.9 (95% CI 0.68-5.0) in all VTE
      patients with elevated APC-PCI complex (above 75th percentile) and 3.6 (95% CI
      1.1-12) in VTE patients without any known risk factor for thrombophilia and with
      elevated s-TM activity. CONCLUSION: The APC-PCI complex concentration, s-TM
      activity and the quotient (s-TM activity)/(s-TM antigen) were higher in VTE
      patients with FV Leiden. The s-TM activity showed higher OR for recurrence of VTE
      in patients without known thrombophilic risk factor. Both methods could be
      sensitive markers of increased risk for venous thrombosis.

PMID- 17499344
TI  - Prognostic significance of p53 and p63 immunolocalisation in primary and matched
      lymph node metastasis in oral squamous cell carcinoma.
AB  - This study evaluates the prognostic significance of p53 and p63
      immunolocalisation in oral squamous cell carcinoma samples from 45 matched
      primary tumors (PT) and lymph node metastases (LNM). Data regarding patient age,
      gender, primary site, histological differentiation, metastasis, disease-free
      survival (DFS) and overall survival (OS) were available. p53 and p63
      immunolabeling was detected in 17 (37.8%) and 23 (51.1%) of the PT, respectively.
      For LNM, there was p53 and p63 labeling in 23 (51.1%) and 26 (57.8%) cases,
      respectively. Most cases showed similar labeling in PT and the corresponding LNM
      (73.3% for p53 and 53.3% for p63, respectively). No statistically significant
      associations were found between p53 and p63 immunolabeling and histological
      differentiation; p63 positive tumors showed higher DFS (p=0.006) and OS
      (p=0.049); and p53-negative tumors had a higher DFS interval (p=0.009). Our
      findings suggest that initially p53-negative tumors and initially p63-positive
      tumors that retain this labeling pattern may follow less aggressive biological
      courses and present better prognoses.

PMID- 17499345
TI  - Sentinel lymph node detection using methylene blue in patients with early stage
      cervical cancer.
AB  - OBJECTIVE: To evaluate the feasibility of sentinel lymph node (SLN) detection in
      patients with cervical cancer using the low-cost methylene blue dye and to
      optimize the application procedure. PATIENTS AND METHODS: Patients with stage
      Ib(1)-IIa cervical cancer and subjected to abdominal radical abdominal
      hysterectomy and pelvic lymphadenectomy were enrolled. Methylene blue, 2-4 ml,
      was injected into the cervical peritumoral area in 77 cases (4 ml patent blue in
      the other four cases) 10-360 min before the incision, and surgically removed
      lymph nodes were examined for the blue lymph nodes that were considered as SLNs.
      RESULTS: High SLN detection rate was successfully achieved when 4 ml of methylene
      blue was applied (93.9%, 46/49). Bilaterally SLN detection rate was significantly
      higher (78.1% vs. 47.1% P=0.027) in cases when the timing of application was more
      than 60 min before surgery than those with timing no more than 30 min. The blue
      color of methylene blue-stained SLNs sustained both in vivo and ex vivo, compared
      with the gradually faded blue color of patent blue that detected in 3 of 4 cases
      unilaterally. In the total of 112 dissected sides, the most common location of
      SLNs was the obturator basin (65.2%, 73/112), followed by external iliac area
      (30.4%, 34/112) and internal iliac area (26.8%, 30/112). Three patients who gave
      false negative results all had enlarged nodes. CONCLUSION: Methylene blue is an
      effective tracer to detect SLNs in patients with early stage cervical cancer. The
      ideal dose and timing of methylene blue application are 4 ml and 60-90 min prior
      surgery, respectively.

PMID- 17499347
TI  - Myeloid sarcoma of the vulva as the presenting symptom in a patient with acute
      myeloid leukemia.
AB  - BACKGROUND: Myeloid sarcoma is a tumor of myeloblasts or immature myeloid cells
      occurring in an extramedullary site. Myeloid sarcoma of female genital tract is
      very rare with no cases of vulvar location reported in English-language
      literature. CASE: A 73-year-old female presented with an indurated mass
      encompassing her left labia majora and vulva. The mass was diagnosed as vulvar
      myeloid sarcoma. The patient's peripheral blood smear revealed Auer rods and
      other findings consistent with a diagnosis of acute myeloid leukemia (M-2 type,
      FAB classification). CONCLUSION: To the best of our knowledge this case is the
      first report in the English-language literature of the myeloid sarcoma of the
      vulva. Correct diagnosis of myeloid sarcoma in an otherwise asymptomatic patient
      is crucial for early administration of antileukemic chemotherapy.

PMID- 17499346
TI  - Pilot study evaluating the efficacy and toxicity of irinotecan plus oral
      etoposide for platinum- and taxane-resistant epithelial ovarian cancer.
AB  - OBJECTIVES: To evaluate the efficacy and toxicity of combination chemotherapy
      with intravenous irinotecan and oral etoposide in women with platinum- and taxane
      resistant epithelial ovarian cancer. METHODS: Between October 2002 and September
      2005, we studied 27 women with platinum- and taxane-resistant epithelial ovarian
      cancer. Irinotecan was administered in an intravenous dose of 70 mg/m(2) as a 90
      min infusion on days 1 and 15 of a 28-day cycle, and etoposide was administered
      in an oral dose of 50 mg/day on days 1 to 21. For heavily pretreated patients,
      the initial dose of irinotecan was lowered to 60 mg/m(2). Treatment cycles were
      repeated until disease progression or unacceptable toxicity. RESULTS: All 27
      patients were eligible and assessable. There were 11 partial responses and 1
      complete response for an overall response rate of 44.4%. The median durations of
      overall response and of stable disease were 11 months and 8 months, respectively.
      The major toxicity was neutropenia (grade 3, 22.2%; grade 4, 37.1%). Diarrhea was
      infrequent and mild, and gastrointestinal toxicity was moderate and manageable.
      Acute myeloid leukemia (M5) developed as a secondary malignancy in 1 patient.
      CONCLUSIONS: The results of our pilot study suggest that a combination of
      irinotecan and oral etoposide is effective and tolerable in women with platinum-
      and taxane-resistant epithelial ovarian cancer.

PMID- 17499348
TI  - The "Leuven" dose-dense paclitaxel/carboplatin regimen in patients with recurrent
      ovarian cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate the "Leuven" dose-dense
      regimen in recurrent ovarian cancer. METHODS: Six courses of paclitaxel (90
      mg/m(2)) and carboplatinum (AUC 4) on d1 and d8 every 3 weeks were administered.
      Response rates were determined using RECIST and Gynaecological Cancer Intergroup
      (GCIG) CA 125 criteria. Platinum resistance was defined as progression during or
      within 6 months after platinum-based chemotherapy. RESULTS: Thirty-three patients
      were included with a median number of prior treatment regimens of 2. Nine
      patients were platinum-resistant and 24 were platinum-sensitive. Three of 8
      patients in the platinum-resistant group and 16 of 21 patients in the platinum
      sensitive group achieved an evaluable response according to RECIST. According to
      the GCIG CA 125 criteria 3 of 7 patients in the platinum-resistant and 17 of 19
      patients in the platinum-sensitive patients responded. In the entire patient
      population evaluable for response (n=29), the median progression-free survival
      (PFS) was 9 months; the median overall survival (OS) was 18 months. Median PFS
      was 6.75 months for the platinum-resistant and 10.5 months for the platinum
      sensitive group. The median OS was 8 months in the platinum-resistant and not yet
      reached in the platinum-sensitive group. Toxicity was mostly bone marrow-related
      with neutropenia grade 3/4 in 34% and neutropenic fever in 2% of courses. Dose
      reduction was necessary in 25% of patients. Nausea and vomiting and fatigue were
      the most frequent non-hematological side effects. CONCLUSION: Dose-dense
      paclitaxel and carboplatin offers a well-tolerated regimen with high response
      rates even in heavily pre-treated and platinum-resistant ovarian cancer.

PMID- 17499349
TI  - Effects of SKF-38393, a dopamine D1 receptor agonist on expression of amphetamine
      induced behavioral sensitization and expression of immediate early gene arc in
      prefrontal cortex of rats.
AB  - Repeated administrations of psychostimulants into rodents produce behavioral
      sensitization. We examined whether a dopamine D1 agonist can reverse behavioral
      sensitization once established by repeated amphetamine (AMP) administrations and
      determined the mRNA expression levels of the D1 and D2 receptors, metabotropic
      glutamate receptor 1 (mGluR1), and activity-regulated cytoskeleton-associated
      protein (arc) in rats. Rats were pretreated with six intermittent AMP injections.
      Following a 14-day withdrawal period, the rats were divided into six groups and
      treated with either SKF-38393 (SKF; dopamine D1 agonist), SCH-23390 (SCH;
      selective D1 antagonist), YM-09151-2 (YM; selective D2 antagonist), SKF+SCH,
      SKF+YM or physiological saline once daily for 5 days. Three days or 4 weeks after
      the reversal treatments, all the rats were rechallenged with AMP. D1 and D2
      antagonist treatments produced no significant decreases in locomotor activity or
      stereotyped behavior rate, respectively. In the SKF treatment group, stereotyped
      behavior rate decreased markedly after the three-day and four-week withdrawal
      periods. SKF+SCH treatment inhibited the effect of SKF treatment. The rats in the
      other groups that received AMP with or without SKF were decapitated 1 h after
      treatment, and the mRNA levels of the D1 and D2 receptors, mGluR1, and arc were
      measured by TaqMan real-time reverse transcriptase-polymerase chain reaction (RT
      PCR). AMP administration significantly increased arc level. SKF also increased
      arc level significantly after the first single injection and after repeated
      injections of AMP during the pretreatment. There was no significant difference in
      arc expression level between the saline and SKF treatment groups after the AMP
      challenge, suggesting that arc expression level is not involved in the reversal
      effects of SKF in AMP sensitization.

PMID- 17499350
TI  - Clean indoor air laws immediately reduce heart attacks.

PMID- 17499351
TI  - Vitamin E analogues as a novel group of mitocans: anti-cancer agents that act by
      targeting mitochondria.
AB  - Mitochondria have recently emerged as new and promising targets for cancer
      prevention and therapy. One of the reasons for this is that mitochondria are
      instrumental to many types of cell death and often lie downstream from the
      initial actions of anti-cancer drugs. Unlike the tumour suppressor gene encoding
      p53 that is notoriously prone to inactivating mutations but whose function is
      essential for induction of apoptosis by DNA-targeting agents (such as doxorubicin
      or 5-fluorouracil), mitochondria present targets that are not so compromised by
      genetic mutation and whose targeting overcomes problems with mutations of
      upstream targets such as p53. We have recently proposed a novel class of anti
      cancer agents, mitocans that exert their anti-cancer activity by destabilising
      mitochondria, promoting the selective induction of apoptotic death in tumour
      cells. In this communication, we review recent findings on mitocans and propose a
      common basis for their mode of action in inducing apoptosis of cancer cells. We
      use as an example the analogues of vitamin E that are proving to be cancer cell
      specific and may soon be developed into efficient anti-cancer drugs.

PMID- 17499352
TI  - An investigation into intersex amphipods and a possible association with
      aquaculture.
AB  - The amphipod, Echinogammarus marinus, is common in sheltered coastal inlets, such
      as estuaries and sea lochs, in Scotland and exhibits increased levels of intersex
      in some contaminated areas. Sea lochs are commonly the location for coastal
      aquaculture development, and some chemicals used in fish-farming are specifically
      designed to target the crustacean nervous system. Therefore it was hypothesised
      that these chemicals may also affect neuro-endocrine pathways, causing
      morphological and reproductive abnormalities in non-target Crustacea. Based upon
      this hypothesis, Echinogammarus marinus amphipods from two different Scottish sea
      lochs containing salmon farms were investigated. Morphology, intersexuality, and
      the incidence of microsporidian parasites were recorded at sites close and at
      distance from fish-farms. Results suggest a higher incidence of intersexuality at
      sites within sea lochs, comparable to that observed in industrially contaminated
      sites elsewhere in Scotland. The data suggest that fish farming activity may
      influence the observed distributions of intersexuality within lochs. Intersex
      specimens were more likely to be infected by microsporidian parasites than non
      intersex specimens. Normal females were found more likely to be infected by
      microsporidian parasites at sites associated with high intersexuality, suggesting
      the parasite as the probable feminiser. The cause(s) for the observed patterns of
      intersexuality are unclear, although suggestions relating to discharges from fish
      farms are discussed.

PMID- 17499353
TI  - Recovery of meiofauna communities following mudflat disturbance by trampling
      associated with crab-tiling.
AB  - The provision of artificial shelters for the collection of crabs, known as crab
      tiling, and the subsequent harvesting of the soft "peeler" crabs for angling
      bait, are associated with trampling disturbance of intertidal mudflats in the
      United Kingdom. Recovery of meiofauna communities following crab-tiling activity
      was investigated on an intertidal mudflat in SW England. Harvesting of
      experimental plots was reproduced six times over a 2-week period. Meiofauna was
      collected at low tides 12h, 36 h and 144 h after treatment. Meiofaunal and
      nematode abundance, and nematode species number, was significantly greater in
      controls compared to crab-tile stations at 12h. At 36 h and 144 h there were no
      significant differences between treatments, indicating recovery had occurred in
      12-36 h. Multivariate analysis showed nematode assemblage composition from
      control plots to be significantly different from crab-tile plots at 12h. No
      significant differences were observed between sediment physical parameters with
      treatment. Results suggest that the predominant effect of disturbance may be
      vibration-induced burial, which causes nematodes to bury deeper into the
      sediment, beyond the depth sampled, and explains the rapid recovery.

PMID- 17499355
TI  - Glucose induces synchronous mitochondrial calcium oscillations in intact
      pancreatic islets.
AB  - Mitochondria shape Ca(2+) signaling and exocytosis by taking up calcium during
      cell activation. In addition, mitochondrial Ca(2+) ([Ca(2+)](M)) stimulates
      respiration and ATP synthesis. Insulin secretion by pancreatic beta-cells is
      coded mainly by oscillations of cytosolic Ca(2+) ([Ca(2+)](C)), but mitochondria
      are also important in excitation-secretion coupling. Here, we have monitored
      [Ca(2+)](M) in single beta-cells within intact mouse islets by imaging
      bioluminescence of targeted aequorins. We find an increase of [Ca(2+)](M) in
      islet-cells in response to stimuli that induce either Ca(2+) entry, such as
      extracellular glucose, tolbutamide or high K(+), or Ca(2+) mobilization from the
      intracellular stores, such as ATP or carbamylcholine. Many cells responded to
      glucose with synchronous [Ca(2+)](M) oscillations, indicating that mitochondrial
      function is coordinated at the whole islet level. Mitochondrial Ca(2+) uptake in
      permeabilized beta-cells increased exponentially with increasing [Ca(2+)], and,
      particularly, it became much faster at [Ca(2+)](C)>2 microM. Since the bulk
      [Ca(2+)](C) signals during stimulation with glucose are smaller than 2 microM,
      mitochondrial Ca(2+) uptake could be not uniform, but to take place
      preferentially from high [Ca(2+)](C) microdomains formed near the mouth of the
      plasma membrane Ca(2+) channels. Measurements of mitochondrial NAD(P)H
      fluorescence in stimulated islets indicated that the [Ca(2+)](M) changes
      evidenced here activated mitochondrial dehydrogenases and therefore they may
      modulate the function of beta-cell mitochondria. Diazoxide, an activator of
      K(ATP), did not modify mitochondrial Ca(2+) uptake.

PMID- 17499356
TI  - In the urochordate Ciona intestinalis zona pellucida domain proteins vary among
      individuals.
AB  - Fertilization in hermaphroditic urochordates requires efficient mechanisms to
      prevent self-mating. By comparing gonadal transcripts of three genetically
      unrelated Ciona intestinalis individuals by suppression subtractive hybridization
      (SSH), we have previously identified a highly polymorphic gene coding for a
      transmembrane receptor which is expressed in follicle cells surrounding the
      mature oocyte [Kurn U, Sommer F, Hemmrich G, Bosch TCG, Khalturin K.
      Allorecogmition in urochordates: identification of a highly variable complement
      receptor-like protein expressed in follicle cells of Ciona. Dev Comp Immunol
      2007; 31(4): 360-71]. Here, we show that in addition to follicle cells, oocytes
      also express variable genes. We have identified four novel Ciona genes coding for
      zona pellucida (ZP) domain proteins which are expressed in developing oocytes and
      which significantly vary among individuals. ZP containing proteins are thought to
      play a crucial and conserved role in controlling fertilization. Our results
      provide strong evidence that in Ciona components of both follicle cells and
      oocytes show a high degree of interindividual variability and, therefore, may
      take part in the prevention of self-mating as well as in the maintenance of
      species-specific fertilization.

PMID- 17499354
TI  - Some assembly required: constructing the elementary units of store-operated Ca2+
      entry.
AB  - The means by which Ca(2+) store depletion evokes the opening of store-operated
      Ca(2+) channels (SOCs) in the plasma membrane of excitable and non-excitable
      cells has been a longstanding mystery. Indirect evidence has supported local
      interactions between the ER and SOCs as well as long-range interactions mediated
      through a diffusible activator. The recent molecular identification of the ER
      Ca(2+) sensor (STIM1) and a subunit of the CRAC channel (Orai1), a prototypic
      SOC, has now made it possible to visualize directly the sequence of events that
      links store depletion to CRAC channel opening. Following store depletion, STIM1
      moves from locations throughout the ER to accumulate in ER subregions positioned
      within 10-25nm of the plasma membrane. Simultaneously, Orai1 gathers at discrete
      sites in the plasma membrane directly opposite STIM1, resulting in local CRAC
      channel activation. These new studies define the elementary units of store
      operated Ca(2+) entry, and reveal an unprecedented mechanism for channel
      activation in which the stimulus brings a channel and its activator/sensor
      together for interaction across apposed membrane compartments. We discuss the
      implications of this choreographic mechanism with regard to Ca(2+) dynamics,
      specificity of Ca(2+) signaling, and the existence of a specialized ER subset
      dedicated to the control of the CRAC channel.

PMID- 17499357
TI  - Identification and analysis of Toll-related genes in the domesticated silkworm,
      Bombyx mori.
AB  - Silkworm (Bombyx mori), a model system for Lepidoptera, has contributed
      enormously to the study of insect immunology especially in humoral immunity. But
      little is known about the molecular mechanism of immune response in the silkworm.
      Toll receptors are a group of evolutionarily ancient proteins, which play a
      crucial role in the innate immunity of both insects and vertebrates. In human,
      Toll-like receptors (TLRs) are the typical pattern recognition receptors for
      different kinds of pathogen molecules. Toll-related receptors in Drosophila,
      however, were thought to function as cytokine receptors in immune response and
      embryogenesis. We have identified 11 putative Toll-related receptors and two Toll
      analogs in the silkworm genome. Phylogenetic analysis of insect Toll family and
      human TLRs showed that BmTolls is grouped with Drosophila Tolls and Anopheles
      Tolls. These putative proteins are typical transmembrane receptors flanked by the
      extracellular leucine-rich repeat (LRR) domain and the cytoplasmic TIR domain.
      Structural prediction of the TIR domain alignment found five stranded sheets and
      five helices, which are alternatingly joined. Microarray data indicated that
      BmToll and BmToll-2 were expressed with remarkable enrichment in the ovary,
      suggesting that they might play a role in the embryogenesis. However, the
      enriched expression of BmToll-2 and -4 in the midgut suggested that the proteins
      they encode may be involved in immune defense. Testis-specific expression of
      BmToll-10 and -11 and BmToLK-2 implies that these may be involved in sex-specific
      biological functions. The RT-PCR results indicated that 10 genes were induced or
      suppressed with different degrees after their immune system was challenged by
      different invaders. Expression profiles of BmTolls and BmToLKs reported here
      provide insight into their role in innate immunity and development.

PMID- 17499359
TI  - Screening ecological risk assessment of persistent organic pollutants in
      Mediterranean sea sediments.
AB  - A screening ecological risk assessment (ERA) was conducted for the first time in
      the Mediterranean basin in order to assess the toxicity posed to the benthic
      community by PCBs, DDTs and HCB in marine sediments. The characterization of the
      exposure was conducted by means of an extensive literature survey, generating a
      database with more than 2000 samples. The effects were assessed by the adoption
      of guidelines previously developed in the literature, because ecotoxicological
      information about persistent organic pollutants (POPs) in the Mediterranean
      sediments was lacking. Existing sediment quality guidelines (SQGs) for the target
      pollutants were compiled and consensus values were calculated for three different
      categories of toxicity, namely threshold effect concentration (TEC), probable
      effect concentration (PEC) and extreme effect concentration (EEC). The
      combination of exposure and effects characterization enabled the identification
      of some areas of concern in the vicinity of industrial and urban locations and in
      the mouths of the main Mediterranean rivers. Beyond the Mediterranean continental
      shelf, the level of toxicity for the benthic community was generally low. The
      evaluation of the toxicity induced by the mixture of the target pollutants
      spotted the importance of DDT contamination in the Mediterranean sediments,
      despite the fact that main inputs to the sea have been significantly reduced
      during the last decades.

PMID- 17499358
TI  - GSK-3 is a viable potential target for therapeutic intervention in bipolar
      disorder.
AB  - Bipolar disorder is a serious psychiatric condition that has been treated for
      over 50 years with lithium. Lithium is a well established glycogen synthase
      kinase-3 (GSK-3) inhibitor, suggesting that manipulating GSK-3 may have
      therapeutic value in treating bipolar disorder. GSK-3 is regulated by a wide
      variety of mechanisms including phosphorylation, binding with protein complexes,
      phosphorylation state of its substrates, cellular localization and
      autoregulation, thus providing a wide number of potential therapeutic mechanisms.
      Mounting evidence suggests that GSK-3 regulation can be used to manage bipolar
      disorder symptoms. Although GSK-3 mutations have not been detected amongst the
      general bipolar population, they have been correlated with females with bipolar
      II and most of the drugs used for successful bipolar disorder treatment regulate
      GSK-3. These drugs produce a weak anti-depressant-like and a strong anti-mania
      like effect in a wide range of animal models tested, mirroring their utility in
      treating bipolar disorder symptoms. Taken together, the evidence suggests that
      targeting GSK-3 may be a means to control the symptoms of bipolar disorder.

PMID- 17499361
TI  - Optically active Ru(II) complexes with a chiral Troger's base ligand and their
      interactions with DNA.
AB  - Three stereoisomers of a Ru(II) complex bearing a chiral bis-phenanthroline
      Troger's base analogue, TBphen2 (1), have been isolated from the reaction of the
      enantiomerically pure precursor complex Lambda- (or Delta-) cis
      [Ru(phen)2(py)2]2+ (phen=1,10-phenanthroline, py=pyridine) with the racemic
      mixture of 1. Each stereoisomer of [Ru(phen)2TBphen2]2+ (2) has been
      characterized by 1H NMR and CD spectroscopy. Electrochemical studies revealed
      that the redox properties of 2 are not influenced by the stereochemistry,
      however, the electrochemical oxidation of the metallic center is irreversible
      because of the diazocine bridge of the TBphen2 ligand. Steady-state emission
      measurements in the presence of calf thymus DNA showed that the DNA binding of
      [Ru(phen)2TBphen2]2+ depends on the stereoisomer and is mainly controlled by the
      absolute configuration of the metal center of the complex. The affinity constant
      for the stereoisomer Delta-S-2 is 10(2) higher than that for Lambda-S-2 and rac
      [Ru(phen)3]2+.

PMID- 17499360
TI  - Effect of succimer chelation therapy on postural balance and gait outcomes in
      children with early exposure to environmental lead.
AB  - This study investigated the influence of succimer chelation therapy in
      eliminating and/or minimizing lead-associated impairments of motor functions such
      as postural balance and locomotion or gait activities. In this study, postural
      balance and functional locomotion or gait were quantitated in 161 children in
      Cincinnati enrolled in a randomized, placebo-controlled, double blind clinical
      trial. In comparison to the placebo group, the succimer therapy group showed
      significantly decreased postural sway during dynamic task performance implying
      improved postural balance. The results from locomotion tests demonstrated
      significant improvements in functional tasks of obstacle crossing and normal
      walking in the succimer treated group. While some beneficial neuromotor effects
      of succimer therapy were observed in the present study there remains several
      unanswered questions such as how long these effects will persist and how succimer
      therapy modifies lead-associated cerebellar deficits manifesting as perturbations
      in vestibular and/or proprioception systems for postural balance and functional
      locomotion.

PMID- 17499362
TI  - The contribution of heme propionate groups to the conformational dynamics
      associated with CO photodissociation from horse heart myoglobin.
AB  - Photoacoustic calorimetry and transient absorption spectroscopy were used to
      study conformational dynamics associated with CO photodissociation from horse
      heart myoglobin (Mb) reconstituted with either Fe protoporphyrin IX dimethylester
      (FePPDME), Fe octaethylporphyrin (FeOEP), or with native Fe protoporphyrin IX
      (FePPIX). The volume and enthalpy changes associated with the Fe-CO bond
      dissociation and formation of a transient deoxyMb intermediate for the
      reconstituted Mbs were found to be similar to those determined for native Mb
      (DeltaV1 = -2.5+/-0.6 ml mol(-1) and DeltaH1 = 8.1+/-3.0 kcal mol(-1)). The
      replacement of FePPIX by FeOEP significantly alters the conformational dynamics
      associated with CO release from protein. Ligand escape from FeOEP reconstituted
      Mb was determined to be roughly a factor of two faster (tau=330 ns) relative to
      native protein (tau=700 ns) and accompanying reaction volume and enthalpy changes
      were also found to be smaller (DeltaV2 = 5.4+/-2.5 ml mol(-1) and DeltaH2 = 0.7+/
      2.2 kcal mol(-1)) than those for native Mb (DeltaV2 = 14.3+/-0.8 ml mol(-1) and
      DeltaH2 = 7.8+/-3.5 kcal mol(-1)). On the other hand, volume and enthalpy changes
      for CO release from FePPIX or FePPDME reconstituted Mb were nearly identical to
      those of the native protein. These results suggest that the hydrogen bonding
      network between heme propionate groups and nearby amino acid residues likely play
      an important role in regulating ligand diffusion through protein matrix.
      Disruption of this network leads to a partially open conformation of protein with
      less restricted ligand access to the heme binding pocket.

PMID- 17499363
TI  - Apoptosis and the cardiac action of insulin-like growth factor I.
AB  - In both cardiac surgical and cardiological settings, clinical interventions used
      to reperfuse the ischemic heart are associated with myocardial damage that is
      likely to influence long-term functional recovery. Ischaemia and reperfusion
      trigger cardiomyocyte death by necrosis and apoptosis. Therefore identifying
      potent cardioprotective agents remains an important goal in cardiac research. In
      a variety of tissues, insulin-like growth factor I (IGF-I) stimulates cellular
      proliferation, somatic growth, and differentiation. In addition, IGF-I inhibits
      apoptotic cell death and therefore plays an important role as a cell survival
      factor. This characteristic would provide an opportunity to both protect (rescue)
      the cardiac myocytes during (after) cardiac insults. In this review, we shall (i)
      describe the characteristics of apoptotic cell death with particular emphasis on
      the heart, (ii) discuss the IGF system with emphasis on the cardiac actions of
      IGF-I under normal and pathological conditions, (iii) elaborate on the potential
      role of IGF-I in myocardial protection, and finally (iv) describe how an improved
      understanding of the cardiac actions of IGF-I may lead to better protective
      clinical strategies in the future. We discuss work by ourselves and others in
      these areas and also consider recent work describing the cellular signaling
      associated with the IGF-I receptor (IGF-IR) in the heart and its potential role
      in regulating excitation-contraction coupling.

PMID- 17499364
TI  - Defining brain-machine interface applications by matching interface performance
      with device requirements.
AB  - Interaction with machines is mediated by human-machine interfaces (HMIs). Brain
      machine interfaces (BMIs) are a particular class of HMIs and have so far been
      studied as a communication means for people who have little or no voluntary
      control of muscle activity. In this context, low-performing interfaces can be
      considered as prosthetic applications. On the other hand, for able-bodied users,
      a BMI would only be practical if conceived as an augmenting interface. In this
      paper, a method is introduced for pointing out effective combinations of
      interfaces and devices for creating real-world applications. First, devices for
      domotics, rehabilitation and assistive robotics, and their requirements, in terms
      of throughput and latency, are described. Second, HMIs are classified and their
      performance described, still in terms of throughput and latency. Then device
      requirements are matched with performance of available interfaces. Simple
      rehabilitation and domotics devices can be easily controlled by means of BMI
      technology. Prosthetic hands and wheelchairs are suitable applications but do not
      attain optimal interactivity. Regarding humanoid robotics, the head and the trunk
      can be controlled by means of BMIs, while other parts require too much
      throughput. Robotic arms, which have been controlled by means of cortical
      invasive interfaces in animal studies, could be the next frontier for non
      invasive BMIs. Combining smart controllers with BMIs could improve interactivity
      and boost BMI applications.

PMID- 17499365
TI  - Post-ovulatory rise of endometrial CD16(-) natural killer cells: in situ
      proliferation of residual cells or selective recruitment from circulating
      peripheral blood?
AB  - In the human endometrium, unique endometrial CD16(-) NK cells acutely increase in
      number after ovulation. Endometrial CD16(-) NK cells are thought to play a role
      in uterus-specific events, such as pregnancy or menstruation, because these NK
      cells are a minor leukocyte subset in circulating peripheral blood and other
      organs. The mechanism underlying the post-ovulatory rise of endometrial CD16(-)
      NK cells is largely unknown. By analogy with other organ systems, two potential
      mechanisms are proposed: one is in situ proliferation of residual cells and the
      other is selective recruitment from circulating peripheral blood. Our recent
      studies focus on the expression and function of potential molecules (including
      cytokines, chemokines and adhesion molecules) involved in these mechanisms in the
      human endometrium, and the regulation of these molecules by ovarian steroids.
      Based upon our findings, we discuss the possibility and relevance of these two
      potential mechanisms.

PMID- 17499366
TI  - Expert opinion: guidelines for the use of natalizumab in multiple sclerosis
      patients previously treated with immunomodulating therapies.
AB  - Natalizumab (Tysabri) (anti-VLA4) is a novel agent for treatment of relapsing
      multiple sclerosis (MS) [Polman C.H., O'Connor P.W., Havrdova E. et al., 2006. A
      randomized, placebo-controlled trial of natalizumab for relapsing multiple
      sclerosis. N. Engl. J. Med. 354, 899-910.]. Controlled trials have shown
      considerable efficacy in preventing relapses, in excess of that seen for other
      EMEA-approved disease modulating drugs. While well-tolerated and generally safe,
      three cases of progressive multifocal leukoencephalopathy (PML) occurred in the
      context of 3 clinical trials encompassing some 3300 patients using this drug in
      multiple sclerosis and Crohn's disease. Immune compromised patients, such as
      those receiving immunosuppressive medications, are at a higher risk of developing
      PML. Natalizumab was recently approved for the treatment of relapsing forms of
      MS. This includes patients who had an inadequate response to other therapies and
      some of these patients will have already received immunosuppressants. These
      agents have the potential to cause prolonged effects on the immune system, even
      after dosing has been discontinued. Determining that these patients are not
      immunocompromised will be an important safety issue to consider prior to the
      initiation of natalizumab therapy. This short report summarizes interdisciplinary
      practical recommendations from specialists in neuroimmunology, rheumatology,
      transplantation medicine and clinical immunology.

PMID- 17499367
TI  - Development of a feasible method to extract somatic coliphages from sludge, soil
      and treated biowaste.
AB  - Extraction of viruses and bacteriophages from sludge, soil and treated biowaste
      requires homogenization, elution, clarification and detoxification
      decontamination steps. Seeding these matrixes with bacteriophages does not
      reproduce what happens in nature. Therefore, naturally occurring matrixes, raw
      sludge, digested and dewatered sludge and compost, containing high numbers of
      somatic coliphages, and soils contaminated with wastewater or raw sludge were
      used in the extraction assays. Based on eluting the bacteriophages with beef
      extract, a feasible method in which the different steps had been optimized has
      been established. The method is feasible, repeatable, robust and applicable in
      routine laboratories. Digested and dewatered sludge has been probed to be useful
      as a reference material for validation studies and for "in lab" quality control.
      The established method includes homogenization by magnetic stirring, elution
      (which is performed at the same time that homogenization) with 10% beef extract
      at neutral pH, clarification by centrifuging at 4000 x g and decontamination by
      filtration through low protein binding 0.22 microm diameter pore size membrane
      filters.

PMID- 17499368
TI  - Development of a one-step immunocapture real-time TaqMan RT-PCR assay for the
      broad spectrum detection of Pepino mosaic virus.
AB  - A real-time reverse-transcription polymerase chain reaction (RT-PCR) was
      developed for efficient detection of genetically diverse Pepino mosaic virus
      (PepMV) isolates. The novel detection system was designed to use a duo-primer
      system targeting the conserved region in the triple gene block 2 (TGB2) gene with
      a single conserved TaqMan probe to broaden its reaction to cover all available
      PepMV strains. This duo-primer real-time RT-PCR assay was evaluated against US1,
      US2, Ch1, Ch2 and 25 field isolates collected from six major commercial tomato
      greenhouse facilities in U.S. and Canada in 2006. Under optimum reaction
      conditions, sensitivity of the detection was as low as 100 fg of purified viral
      RNA. This assay was also evaluated for its efficiency in detecting PepMV in
      various levels of contaminated seed samples. Using immuno-capture sample
      preparation, real-time RT-PCR was able to detect PepMV in one infested seed in
      1000. This level of sensitivity indicated that the one-step immuno-capture duo
      primer TaqMan real-time RT-PCR developed in the present study could be used for
      routine seed health assays.

PMID- 17499369
TI  - Protection of pigs from lethal challenge by a DNA vaccine based on an alphavirus
      replicon expressing the E2 glycoprotein of classical swine fever virus.
AB  - In a previous study, it has been shown that a Semliki Forest virus (SFV) replicon
      vectored DNA vaccine (pSFV1CS-E2) expressing the E2 glycoprotein of classical
      swine fever virus (CSFV) conferred full protection for pigs immunized three times
      with 600 microg of the vaccine. This study was designed to evaluate further the
      efficacy of the vaccine with lower dosage and fewer inoculations. Pigs were
      immunized twice with 100 microg of pSFV1CS-E2 (n=5) or control plasmid pSFV1CS
      (n=3), respectively, and challenged with virulent Shimen strain 6 weeks following
      the booster immunization. Pigs immunized with pSFV1CS-E2 developed high titers of
      specific neutralizing antibodies against CSFV after the booster, and the antibody
      titers increased rapidly upon challenge. The immunized animals showed no clinical
      symptoms except short-term fever and low-level viremia, whereas, the control pigs
      immunized with the control plasmid produced no detectable antibody prior to
      challenge, and showed obvious clinical signs following challenge, and two pigs
      died of illness. All control animals developed extended viremia as detected by
      nested RT-PCR and real-time RT-PCR. Severe pathologic lesions typical of CSFV
      infection were observed at necropsy. It is concluded that the alphavirus replicon
      vectored DNA-based vaccine can be a potential marker vaccine against CSFV.

PMID- 17499370
TI  - Antagonism of nucleus accumbens M(2) muscarinic receptors disrupts operant
      responding for sucrose under a progressive ratio reinforcement schedule.
AB  - Diverse cholinergic signaling mechanisms regulate the excitability of striatal
      principal neurons and modulate striatal-dependent behavior. These effects are
      mediated, in part, by action at muscarinic receptors (mAChR), subtypes of which
      exhibit distinct patterns of expression across striatal neuronal populations. Non
      selective mAChR blockade within the nucleus accumbens (NAc) has been shown to
      disrupt operant responding for food and to inhibit food consumption. However, the
      specific receptor subtypes mediating these effects are not known. Thus, we
      evaluated effects of intra-NAc infusions of pirenzepine and methoctramine, mAChR
      antagonisits with distinct binding affinity profiles, on operant responding for
      sucrose reward under a progressive ratio (PR) reinforcement schedule. Moderate to
      high doses of methoctramine disrupted operant responding and reduced behavioral
      breakpoint. In contrast, pirenzepine failed to impact operant performance at any
      dose tested. Methoctramine failed to affect latencies to complete appetitive
      consummatory response sequences or to impact measures of acoustic startle,
      suggesting that its' disruptive effects on operant behavior were not consequent
      to gross motor impairment. Since methoctramine has a greater affinity for M(2)
      receptors compared to pirenzepine, which has a greater relative affinity for M(1)
      and M(3) receptors, these findings suggest that M(2) mAChRs within the NAc
      regulate behavioral processes underling the acquisition of reward.

PMID- 17499371
TI  - Nuclear gyrB encodes a functional subunit of the Plasmodium falciparum gyrase
      that is involved in apicoplast DNA replication.
AB  - The DNA replication machinery of the Plasmodium falciparum apicoplast is a
      validated drug target. Nuclear-encoded gyrase subunits are predicted to play a
      critical role in maintaining DNA topology during the D-loop/bi-directional ori
      replication process of the parasite. We show the presence of P. falciparum gyrase
      subunits in parasite lysates by using antibodies generated against recombinant
      gyrase A and B. The ATPase activity of PfGyrB was inhibited by novobiocin that
      also caused parasite death in culture. Reduction of apicoplast/nuclear DNA ratio
      in the presence of novobiocin indicated that the drug targets apicoplast DNA
      replication. Molecular modeling of gyrase A and B subunits revealed extensive
      fold conservation with the Escherichia coli counterparts as well as the presence
      of a long disordered loop adjacent to the ATPase domain of PfGyrB. Our results
      have implications for development of PfGyrB as a drug target against malaria.

PMID- 17499373
TI  - Proton beam therapy - do we need the randomised trials and can we do them?

PMID- 17499374
TI  - Proton therapy - a systematic review of clinical effectiveness.
AB  - BACKGROUND AND PURPOSE: Proton therapy is an emerging treatment modality for
      cancer that may have distinct advantages over conventional radiotherapy. This
      relates to its ability to confine the high-dose treatment area to the tumour
      volume and thus minimizing radiation dose to surrounding normal tissue. Several
      proton facilities are currently operating or under planning world-wide - in the
      United States, Asia and Europe. Until now no systematic review assessing the
      clinical effectiveness of this treatment modality has been published. MATERIALS
      AND METHODS: A systematic review of published studies that investigated clinical
      efficacy of proton therapy of cancer. RESULTS: We included 54 publications: 4
      randomized controlled trials (RCTs) reported in 5 publications, 5 comparative
      studies and 44 case series. Two RCTs addressed proton irradiation as a boost
      following conventional radiation therapy for prostate cancer, where one
      demonstrated improved biochemical local control for the highest dose group
      without increased serious complication rates. Proton therapy has been used to
      treat a large number of patients with ocular tumours, but except for one low
      quality RCT, no proper comparison with other treatment alternatives has been
      undertaken. Proton therapy offers the option to deliver higher radiation doses
      and/or better confinement of the treatment of intracranial tumours in children
      and adults, but reported studies are heterogeneous in design and do not allow for
      strict conclusions. CONCLUSION: The evidence on clinical efficacy of proton
      therapy relies to a large extent on non-controlled studies, and thus is
      associated with low level of evidence according to standard heath technology
      assessment and evidence based medicine criteria.

PMID- 17499372
TI  - Differences in presentation and management of stable angina from East to West in
      Europe: a comparison between Poland and the UK.
AB  - AIMS: Variations in the resources, stability and priorities of health care
      systems conceivably affect their capacity to implement health care reform and
      ensure an evidence based approach to health care. Such variation may partially
      account for differences in cardiovascular mortality rates between former
      communist states in Central Europe and Western European countries, but specific
      data on this subject is sparse. The aim of this study was to compare the
      presentation of stable angina to cardiology services in Poland vs. the United
      Kingdom, the management of the condition in relation to existing European
      guidelines and clinical outcome. METHODS AND RESULTS: Data was collected as part
      of a prospective observational cohort study of stable angina in Europe.
      Information was recorded on referral patterns, clinical presentation and the use
      of pharmacological therapies, investigations, revascularisation and
      cardiovascular events during 1 year of follow up. A total of 571 patients with
      stable angina were enrolled in Poland and 319 in the UK. Patients presenting to
      cardiology services in Poland were less likely to be referred by a primary care
      physician, younger, and had more adverse clinical risk predictors at
      presentation. Non-invasive investigation and coronary angiography were performed
      less frequently in Poland, but waiting times for invasive assessment were
      shorter. European guidelines with regard to the use of evidence based secondary
      preventative medical therapy were applied widely by cardiologists in both
      countries. No differences were observed in rates of cardiovascular events.
      CONCLUSIONS: The use of evidence based pharmacological therapy was equally high
      in both countries, but guidelines regarding investigation were less completely
      adhered to in Poland, where invasive assessment and subsequent management was
      prompt but only performed in a highly selected proportion of the population with
      stable angina.

PMID- 17499375
TI  - Effects of acute dopamine depletion on the electrophysiological properties of
      striatal neurons.
AB  - The striatum, the main input nucleus of basal ganglia, receives a massive
      innervation from the entire cerebral cortex and is in charge of the detection of
      behaviorally relevant signals. In turn, via its projections to the output nuclei
      of basal ganglia, the striatum contributes to the organization of appropriate
      compartmental responses. Substantia nigra pars compacta dopaminergic neurons
      project predominantly to the striatum and regulate striatal functions.
      Implications of dopaminergic receptors on the physiology of striatal neurons are
      now well documented. By contrast, the effects of acute dopamine depletion on
      striatal neurons remain poorly explored. Here, the alpha-methyl-para-tyrosine was
      used to deplete dopamine from rat brain slices. We analyzed the consequences of a
      alpha-methyl-para-tyrosine treatment on membrane properties of striatal neurons:
      the medium-sized spiny neurons and the interneurons (GABAergic, cholinergic and
      NO-synthase). After acute dopamine depletion, medium-sized spiny neurons became
      more excitable. GABAergic interneurons became less excitable whereas cholinergic
      cells displayed an increased excitability. NO-synthase-containing interneurons
      did not show noticeable changes in their excitability. Such membrane properties
      changes indicate that striatal circuits should undergo major alteration in
      cortico-basal ganglia information processing.

PMID- 17499376
TI  - Antigenic characterization of severe acute respiratory syndrome-coronavirus
      nucleocapsid protein expressed in insect cells: The effect of phosphorylation on
      immunoreactivity and specificity.
AB  - The nucleocapsid (N) protein of severe acute respiratory syndrome-coronavirus
      (SARS-CoV) is involved in the pathological reaction to SARS and is a key antigen
      for the development of a sensitive diagnostic assay. However, the antigenic
      properties of this N protein are largely unknown. To facilitate the studies on
      the function and antigenicity of the SARS-CoV N protein, 6x histidine-tagged
      recombinant SARS-CoV N (rSARS-N) with a molecular mass of 46 and 48kDa was
      successfully produced using the recombinant baculovirus system in insect cells.
      The rSARS-N expressed in insect cells (BrSARS-N) showed remarkably higher
      specificity and immunoreactivity than rSARS-N expressed in E. coli (ErSARS-N).
      Most of all, BrSARS-N proteins were expressed as a highly phosphorylated form
      with a molecular mass of 48kDa, but ErSARS-N was a nonphosphorylated protein. In
      further analysis to determine the correlation between the phosphorylation and the
      antigenicity of SARS-N protein, dephosphorylated SARS-N protein treated with
      protein phosphatase 1 (PP1) remarkably enhanced the cross-reactivity against SARS
      negative serum and considerably reduced immunoreactivity with SARS-N mAb. These
      results suggest that the phosphorylation plays an important role in the
      immunoreactivity and specificity of SARS-N protein. Therefore, the BrSARS-N
      protein may be useful for the development of highly sensitive and specific assays
      to determine SARS infection and for further research of SARS-N pathology.

PMID- 17499377
TI  - Construction and characterization of porcine circovirus type 2 carrying a genetic
      marker strain.
AB  - Porcine circovirus type 2 (PCV2) is the primary causative agent of post-weaning
      multisystemic wasting syndrome in pigs. To generate a genetic marker strain of
      PCV2, the full-length genome of the virus was amplified using PCR, and two copies
      of the genome were ligated in tandem to construct an infectious molecular clone.
      A Sal I restriction enzyme site was inserted into the clone as a genetic marker,
      and the recombinant plasmid was transfected into porcine kidney cells to generate
      mutant virus. The antigenicity of the recovered virus was confirmed by
      immunoperoxidase monolayer assay. The viral antigen was visualized in the nucleus
      and cytoplasm of the virus-infected cells. The viral genome could be
      differentiated from the wild-type parent by PCR and restriction fragment length
      polymorphism (PCR-RFLP). The mutant virus was stable on multiplication through 60
      passages in cell culture; the highest titer reached was 10(6.6)TCID(50)/ml. Four
      35-day-old unvaccinated piglets were inoculated with the virus by the intranasal
      and intravenous routes. Two of the virus-infected pigs developed high
      temperatures, progressive weight loss, and swollen lymph nodes. The viral antigen
      and nucleic acid were detected in numerous tissues of the pigs. The results
      indicate that the genetic marker strain should be a useful tool in studies on
      pathogenesis, vaccination, and molecular diagnosis of PCV2.

PMID- 17499378
TI  - Animal models and vaccines for SARS-CoV infection.
AB  - We summarize findings of SARS-CoV infections in several animal models each of
      which support viral replication in lungs accompanied by histopathological changes
      and/or clinical signs of illness to varying degrees. New findings are reported on
      SARS-CoV replication and associated pathology in two additional strains (C57BL/6
      and 129S6) of aged mice. We also provide new comparative data on viral
      replication and associated pathology following infection of golden Syrian
      hamsters with various SARS-CoV strains and report the levels of neutralizing
      antibody titers following these infections and the cross-protective efficacy of
      infection with these strains in protecting against heterologous challenge.
      Finally, we summarize findings of a variety of vaccine approaches and discuss the
      available in vitro and in vivo data addressing the potential for disease
      enhancement following re-infection in animals previously vaccinated against or
      infected with SARS-CoV.

PMID- 17499379
TI  - Immunological evaluation of Escherichia coli expressed E2 protein of Western
      equine encephalitis virus.
AB  - The Western equine encephalitis virus (WEEV) is a potential Biological Warfare
      (BW) agent. The WEEV is endemic in western Canada and has caused epidemics of
      "sleeping sickness" with a mortality rate of 7-9%. The E2 glycoprotein is a
      structural component of the WEEV and elicits production of neutralizing
      antibodies against the virus following an infection event. The envelope
      glycoprotein E2 is considered as the major target protein for the development of
      vaccines because it includes epitopes that elicit neutralizing antibodies. This
      report describes the successful cloning of the E2 gene of WEEV and expression in
      Escherichia coli as inclusion bodies. The inclusion bodies were successfully
      solubilized, refolded and the immunogenicity of this non-glycosylated protein was
      assessed in BALB/c mice. Recombinant E2 (rE2) protein was specifically and
      strongly recognized by inactivated WEEV-immunized mice serum sample on ELISA,
      suggesting that E. coli derived rE2 protein retained at least some functional
      characteristics of its native conformation. The immunogenicity of the refolded
      rE2 protein was demonstrated by strong humoral and cell mediated immune (CMI)
      responses in rE2-immunized BALB/c mice. The current study also demonstrated that
      rE2-immunized mice could be partially protected from lethal challenge of WEEV.

PMID- 17499380
TI  - Long terminal repeat sequences from virulent and attenuated equine infectious
      anemia virus demonstrate distinct promoter activities.
AB  - In the early 1970s, the Chinese Equine Infectious Anemia Virus (EIAV) vaccine,
      EIAV(DLA), was developed through successive passages of a wild-type virulent
      virus (EIAV(L)) in donkeys in vivo and then in donkey macrophages in vitro. EIAV
      attenuation and cell tropism adaptation are associated with changes in both
      envelope and long terminal repeat (LTR). However, specific LTR changes during
      Chinese EIAV attenuation have not been demonstrated. In this study, we compared
      LTR sequences from both virulent and attenuated EIAV strains and documented the
      diversities of LTR sequence from in vivo and in vitro infections. We found that
      EIAV LTRs of virulent strains were homologous, while EIAV vaccine have variable
      LTRs. Interestingly, experimental inoculation of EIAV(DLA) into a horse resulted
      in a restriction of the LTR variation. Furthermore, LTRs from EIAV(DLA) showed
      higher Tat transactivated activity than LTRs from virulent strains. By using
      chimeric clones of wild-type LTR and vaccine LTR, the main difference of activity
      was mapped to the changes of R region, rather than U3 region.

PMID- 17499381
TI  - A point mutation in the putative ATP binding site of the pseudorabies virus US3
      protein kinase prevents Bad phosphorylation and cell survival following apoptosis
      induction.
AB  - The multifunctional US3 protein kinase is conserved among alphaherpesviruses.
      Like the herpes simplex virus US3 protein kinase, the pseudorabies virus (PRV)
      US3 protein confers resistance against apoptosis. In the current report, we
      introduced a point mutation in the putative ATP binding site of the PRV US3
      protein kinase. We found that, in contrast to the wild type PRV US3, the point
      mutated PRV US3 does not protect cells from apoptosis induced by PRV infection or
      staurosporine treatment. In addition, we found that the presence of wild type PRV
      US3, but not of the point-mutated PRV US3, results in phosphorylation of the pro
      apoptotic Bad protein in PRV-infected ST and HEp-2 cells. In PRV-infected ST
      cells, but not in HEp-2 cells, an additional, US3- and phosphorylation
      independent alteration of Bad could be observed. These results suggest that the
      kinase activity of the US3 protein of PRV is crucial to protect cells from
      apoptotic cell death during infection, at least partly by leading to
      phosphorylation of the pro-apoptotic Bad protein.

PMID- 17499383
TI  - The stars and stripes of animal bodies: evolution of regulatory elements
      mediating pigment and bristle patterns in Drosophila.
AB  - Evolution has generated enormous morphological diversity in animals and one of
      the genetic processes that might have contributed to this is evolution of the cis
      regulatory sequences responsible for the temporal and spatial expression of genes
      regulating embryonic development. This could be particularly relevant to
      pleiotropic genes with multiple independently acting regulatory modules. Loss or
      gain of modules enables altered expression without loss of other functions. Here
      I focus on recent studies correlating differences in morphological traits between
      related species of Drosophila to changes in cis-regulatory sequences. They show
      that ancestral regulatory modules have evolved to mediate different
      transcriptional outputs and suggest that evolution of cis-regulatory sequences
      might reflect a general mechanism driving evolutionary change.

PMID- 17499382
TI  - Epitope mapping of HSV-1 glycoprotein K (gK) reveals a T cell epitope located
      within the signal domain of gK.
AB  - Glycoprotein K (gK) is a virion envelope component of herpes simplex virus types
      1 (HSV-1) and 2 (HSV-2), which plays an important role in virion morphogenesis
      and egress. We previously demonstrated that immunization of mice with gK, but not
      with any of the 10 other HSV-1 glycoproteins, resulted in exacerbation of corneal
      scarring and herpetic dermatitis following ocular HSV-1 infection. However,
      little is known about the gK epitope(s) that is (are) involved in T cell
      activities in vitro or in vivo. Thus, epitope mapping of gK was performed using a
      panel of 15-mer peptides with five-amino acid overlaps spanning the full-length
      gK, and four expressed gK recombinant proteins representing different regions of
      gK. Epitope mapping within the gK polypeptide defined the amino acid sequence
      STVVLITAYGLVLVW as the predominant CD4(+) and CD8(+) T cell stimulatory region
      both in vitro and in vivo. IFN-gamma expression by CD4(+) T cells was CD8(+) T
      cells-dependent. This immunodominant epitope is located within the signal
      sequence of the gK polypeptide and is highly conserved in HSV-1 and HSV-2
      strains. Using prediction algorithms, the peptide is predicted to bind to
      numerous MHC class I and class II molecules.

PMID- 17499384
TI  - Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage
      tissue engineering.
AB  - Regeneration of bone and cartilage defects can be accelerated by localized
      delivery of appropriate growth factors incorporated within biodegradable
      carriers. The carrier essentially allows the impregnated growth factor to release
      at a desirable rate and concentration, and to linger at injury sites for a
      sufficient time to recruit progenitors and stimulate tissue healing processes. In
      addition, the carrier can be formulated to have particular structure to
      facilitate cellular infiltration and growth. In this review, we present a summary
      of growth factor delivery carrier systems for bone and cartilage tissue
      engineering. Firstly, we describe a list of growth factors implicated in repair
      and regeneration of bone and cartilage by addressing their biological effects at
      different stages of the healing process. General requirements for localized
      growth factor delivery carriers are then discussed. We also provide selective
      examples of material types (natural and synthetic polymers, inorganic materials,
      and their composites) and fabricated forms of the carrier (porous scaffolds,
      microparticles, and hydrogels), highlighting the dose-dependent efficacy, release
      kinetics, animal models, and restored tissue types. Extensive discussion on
      issues involving currently investigated carriers for bone and cartilage tissue
      engineering approaches may illustrate future paths toward the development of an
      ideal growth factor delivery system.

PMID- 17499386
TI  - Annual abdominal ultrasonographic examination after curative NSCLC resection.
AB  - BACKGROUND: There is no established follow-up strategy in non-small cell lung
      cancer patients after complete resection. Follow-up regimens are different
      between nations, institutions, and surgeons. We tried to investigate the role of
      annual abdominal ultrasonographic examination in completely resected NSCLC
      patients. METHODS: We reviewed 265 consecutive patients who had their NSCLC
      completely resected at our institution from July 1992 through December 2000 and
      were followed by a single surgeon. Annual abdominal ultrasonography was performed
      until 5 years after resection. Chest CT and abdominal CT are not included in our
      routine follow-up program. Instead, we used ultrasonography to survey the abdomen
      because abdominal ultrasonography is less costly than abdominal CT, is non
      invasive, and does not require contrast media. RESULTS: A total of 892
      ultrasonographic examinations were performed. Fifty-nine (22.3%) patients
      developed recurrence. Annual ultrasonography detected lesions suspicious of
      recurrence in 15 patients. Further work-up diagnosed NSCLC recurrence in 2 (0.8%)
      patients (multiple liver metastases in one and right adrenal metastasis in one).
      The two patients soon developed disseminated disease and died in less than a
      year. CONCLUSIONS: Annual abdominal ultrasonography in the follow-up protocol for
      completely resected NSCLC patients was not beneficial. Our experience in the
      present study may be used as valid evidence to exclude abdominal ultrasonography
      from future trials comparing follow-up regimens after complete resection of
      NSCLC. A better follow-up strategy needs to be established.

PMID- 17499387
TI  - Nitric oxide protects against polyethylene glycol-induced oxidative damage in two
      ecotypes of reed suspension cultures.
AB  - Dune reed (DR) is the more tolerant ecotype of reed to environmental stresses
      than swamp reed (SR). Under osmotic stress mediated by polyethylene glycol (PEG
      6000), the suspension culture of SR showed higher ion leakage, and more oxidative
      damage to the membrane lipids and proteins was observed compared with the
      relatively tolerant DR suspension culture. Treatment with sodium nitroprusside
      (SNP) can significantly alleviated PEG-induced ion leakage, thiobarbituric acid
      reactive substances (TBARS) and carbonyl contents increase in SR suspension
      culture. The levels of H(2)O(2) and O(2)(-) were reduced, and the activities of
      antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and
      ascorbate peroxidase (APX) were increased in both suspension cultures in the
      presence of SNP under osmotic stress, but lipoxygenase (LOX) activity was
      inhibited. 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
      (PTIO), a specific Nitric oxide (NO) scavenger, blocked the SNP-mediated
      protection. Depletion of endogenous NO with PTIO strongly enhanced oxidative
      damage in DR compared with that of PEG treatment alone, whereas had no effect on
      SR. Moreover, NO production increased significantly in DR while kept stable in SR
      under osmotic stress. Taken together, these results suggest that PEG induced NO
      release in DR but not SR can effectively protect against oxidative damage and
      confer an increased tolerance to osmotic stress in DR suspension culture.

PMID- 17499388
TI  - Refining dermatology journal impact factors using PageRank.
AB  - BACKGROUND: Thomson Institute for Scientific Information's journal impact factor,
      the most common measure of journal status, is based on crude citation counts that
      do not account for the quality of the journals where the citations originate.
      This study examines how accounting for citation origin affects the impact factor
      ranking of dermatology journals. METHODS: The 2003 impact factors of dermatology
      journals were adjusted by a weighted PageRank algorithm that assigned greater
      weight to citations originating in more frequently cited journals. RESULTS:
      Adjusting for citation origin moved the rank of the Journal of the American
      Academy of Dermatology higher than that of the Archives of Dermatology (third to
      second) but did not affect the ranking of the highest impact dermatology journal,
      the Journal of Investigative Dermatology. The dermatology journals most
      positively affected by adjusting for citation origin were Contact Dermatitis
      (moving from 22nd to 7th in rankings) and Burns (21st to 10th). Dermatology
      journals most negatively affected were Seminars in Cutaneous Medicine and Surgery
      (5th to 14th), the Journal of Cutaneous Medicine and Surgery (19th to 27th), and
      the Journal of Investigative Dermatology Symposium Proceedings (26th to 34th).
      LIMITATIONS: Current measures of dermatology journal status do not incorporate
      survey data from dermatologists regarding which journals dermatologists esteem
      most. CONCLUSION: Adjusting for citation origin provides a more refined measure
      of journal status and changes relative dermatology journal rankings.

PMID- 17499389
TI  - Patient preferences for facial sunscreens: a split-face, randomized, blinded
      trial.
AB  - BACKGROUND: Sunscreen use is a widely accepted method of primary prevention
      against skin cancer, sunburn, and photoaging. However, many people do not
      routinely apply sunscreen because they find application objectionable. OBJECTIVE:
      To determine which types of sunscreen subjects are willing to use on more than
      one occasion. METHODS: A split-face, randomized, blinded trial of commercially
      available sunscreens was performed among 139 community members in Rochester,
      Minnesota. RESULTS: Subjects were significantly more likely to indicate that they
      would use alcohol-based spray sunscreen again than two of the seven sunscreens
      assessed (P < .05). This sunscreen was endorsed as being less greasy, less likely
      to leave a film, and less likely to leave them feeling hot and sweaty than at
      least two of the other sunscreens. LIMITATIONS: Only a representative selection
      of commonly available sunscreens was tested. CONCLUSION: An alcohol-based spray
      formulation of sunscreen was rated more favorable. Recommendations to use alcohol
      based spray sunscreens may increase patient compliance.

PMID- 17499390
TI  - Introduction to four papers on Curt Richter and analysis of his scientific
      practice.
AB  - Curt Richter was one of the founders of our field. He did outstanding research
      for over 60 years. Richter did fundamental work in appetite for food and minerals
      in the 1930s and discovered the homeostatic functions of ingestive behavior. This
      paper introduces four papers on specific topics of his work by contemporaneous
      experts. Each of the papers reviews Richter's experiments and then shows how the
      problem developed since he left it. The papers demonstrate that providing the
      historical basis for contemporary science is not only instructive, it is also
      heuristic for the science waiting to be done. In addition to introducing the four
      papers, I analyze the scientific ideas, values, and men that influenced Richter's
      scientific practice. I conclude that Claude Bernard, Walter Cannon, Francois
      Magendie, and Maurice Arthus were important for Richter's scientific ideas and
      values, but it was the joy of research that explains his experimental success for
      over 60 years.

PMID- 17499385
TI  - Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue
      engineering.
AB  - Current treatments for diseases and trauma of dental, oral and craniofacial (DOC)
      structures rely on durable materials such as amalgam and synthetic materials, or
      autologous tissue grafts. A paradigm shift has taken place to utilize tissue
      engineering and drug delivery approaches towards the regeneration of these
      structures. Several prototypes of DOC structures have been regenerated such as
      temporomandibular joint (TMJ) condyle, cranial sutures, tooth structures and
      periodontium components. However, many challenges remain when taking in
      consideration the high demand for esthetics of DOC structures, the complex
      environment and yet minimal scar formation in the oral cavity, and the need for
      accommodating multiple tissue phenotypes. This review highlights recent advances
      in the regeneration of DOC structures, including the tooth, periodontium, TMJ,
      cranial sutures and implant dentistry, with specific emphasis on controlled
      release of signaling cues for stem cells, biomaterial matrices and scaffolds, and
      integrated tissue engineering approaches.

PMID- 17499391
TI  - Utility of routine testing for patients with asymptomatic severe blood pressure
      elevation in the emergency department.
AB  - STUDY OBJECTIVE: Recommendations for the treatment of emergency department (ED)
      patients with asymptomatic severely elevated blood pressure advise assessment for
      occult, acute hypertensive target-organ damage. This study determines the
      prevalence of unanticipated, clinically meaningful test abnormalities in ED
      patients with asymptomatic severely elevated blood pressure. METHODS: This was a
      prospective observational study at 3 urban academic EDs. Consecutive patients
      with systolic blood pressure greater than or equal to 180 mm Hg or diastolic
      blood pressure greater than or equal to 110 mm Hg on 2 measurements were enrolled
      if they denied symptoms of hypertensive emergency. A basic metabolic panel,
      urinalysis, ECG, CBC count, and chest radiograph were obtained. Treating
      physicians were interviewed about the indication for each test and whether an
      abnormal result was anticipated according to clinical findings. When test results
      were available, physicians were asked whether abnormal findings were clinically
      meaningful, defined as leading to unanticipated hospitalization, medication
      modification, or further immediate evaluation. The primary outcome was the
      prevalence of unanticipated clinically meaningful test abnormalities. RESULTS:
      One hundred nine patients with asymptomatic severely elevated blood pressure were
      enrolled. Unanticipated abnormal test results were noted in 57 (52%) patients.
      Clinically meaningful unanticipated test abnormalities were found in 7 (6%)
      patients: basic metabolic panel in 2 (2%), CBC count in 3 (3%), urinalysis in 3
      (4%), ECG in 2 (2%), and chest radiograph in 1 (1%). Five patients (5%) had
      abnormalities assessed as possible manifestations of acute hypertensive target
      organ injury; none had abnormalities clearly related to severely elevated blood
      pressure. CONCLUSION: Screening tests of urban ED patients with asymptomatic
      severely elevated blood pressure infrequently detect unanticipated hypertension
      related abnormalities that alter ED management.

PMID- 17499392
TI  - PET imaging of amyloid deposition in patients with mild cognitive impairment.
AB  - It is of great clinical value to identify subjects at a high risk of developing
      AD. We previously found that the amyloid positron emission tomography (PET)
      tracer PIB showed a robust difference in retention in the brain between AD
      patients and healthy controls (HC). Twenty-one patients diagnosed with MCI (mean
      age 63.3+/-7.8 (S.D.) years) underwent PET studies with (11)C-PIB, and (18)F
      fluoro-deoxy-glucose (FDG) to measure cerebral glucose metabolism, as well as
      assessment of cognitive function and CSF sampling. Reference group data from 27
      AD patients and 6 healthy controls, respectively, were used for comparison. The
      mean cortical PIB retention for the MCI patients was intermediate compared to HC
      and AD. Seven MCI patients that later at clinical follow-up converted to AD
      (8.1+/-6.0 (S.D.) months) showed significant higher PIB retention compared to non
      converting MCI patients and HC, respectively (ps<0.01). The PIB retention in MCI
      converters was comparable to AD patients (p>0.01). Correlations were observed in
      the MCI patients between PIB retention and CSF Abeta(1-42), total Tau and
      episodic memory, respectively.

PMID- 17499393
TI  - Chemotherapy of leishmaniasis. Part VII: synthesis and bioevaluation of
      substituted terpenyl pyrimidines.
AB  - Some novel 4-N-substituted terpenyl pyrimidines 5(a-d) and 7(a-g) have been
      synthesized using novel synthetic methods. The compounds were screened for in
      vivo antileishmanial screening. When compared to 4-thiomethoxy substituted
      pyrimidine 2 4-N-substituted terpenyl pyrimidines 5(a-d) and 7(a-g) were found
      inactive.

PMID- 17499394
TI  - [Pyoderma gangrenosum and Churg-Strauss syndrome].
AB  - INTRODUCTION: Pyoderma gangrenosum (PG) is an unusual dermatitis witch is
      associated at least in half of the cases with a systemic illness. CASE RECORD: A
      54 year-old woman suffering from Churg and Strauss syndrome has been monitored
      for many years. She was hospitalized in dermatology unit for a PG without showing
      any activity signs of her angeitis. After a well conducted localized treatment,
      the cutaneous lesions rapidly improved. DISCUSSION: PG physiopathology is still
      not well known, but its interest lies in the fact of the high number of
      associated internal pathologies and is probably linked to granulomatosis such as
      Churg and Strauss angeitis.

PMID- 17499395
TI  - Problem based learning in midwifery--the students' perspective.
AB  - Problem based learning (PBL) has been adopted in many settings for the education
      of health professionals. It has generally been evaluated well by students
      although much of the literature comes from medical education. The aim of this
      study was to ascertain the views of student midwives at the beginning and at the
      end of their programme and three months after graduation about the use of a PBL
      based programme in midwifery. Eight focus groups were conducted with students
      whilst undertaking a PBL programme from both a shortened and three year programme
      across two sites. A questionnaire was sent 3 months after graduation to midwives
      who had completed the programme. Key themes which emerged from this study were
      that although students gained skills in information retrieval and critique some
      did not always feel well prepared for practice. The focus on individual
      presentations in the tutorial tended to be interpreted as performance rather than
      discussion in a spirit of enquiry. Students reported being particularly anxious
      at the beginning of their programme about their learning. They felt that their
      experience was dependent upon the participation and motivation of the group
      members.

PMID- 17499396
TI  - Loss of skeletal muscle mass in aging: examining the relationship of starvation,
      sarcopenia and cachexia.
AB  - A loss of body weight or skeletal muscle mass is common in older persons and is a
      harbinger of poor outcome. Involuntary weight loss can be categorized into three
      primary etiologies of starvation, sarcopenia, and cachexia. Starvation results in
      a loss of body fat and non-fat mass due to inadequate intake of protein and
      energy. Sarcopenia is associated with a reduction in muscle mass and strength
      occurring with normal aging, associated with a reduction in motor unit number and
      atrophy of muscle fibers, especially the type IIa fibers. The loss of muscle mass
      with aging is clinically important because it leads to diminished strength and
      exercise capacity. Cachexia is widely recognized as severe wasting accompanying
      disease states such as cancer or immunodeficiency disease, but does not have a
      universally accepted definition. The key clinical question is whether these
      changes in body composition are distinct entities or represent an interdependent
      continuum. The importance of defining the distinction lies in developing a
      targeted therapeutic approach to skeletal muscle loss and muscle strength in
      older persons. Failure to distinguish among these causes of skeletal muscle loss
      often results in frustration over the clinical response to therapeutic
      interventions.

PMID- 17499397
TI  - Does concomitant glucose and glutamine supplementation change the response of
      glutamine synthetase to fasting in healthy adult rats?
AB  - BACKGROUND & AIMS: Glutamine synthetase (GS), a key enzyme in the glutamine
      synthesis, is thus crucial in glutamine homeostasis. GS is known to be up
      regulated by fasting and inhibited by glutamine supplementation. The aim of this
      study was to determine whether the presence of glucose in glutamine
      supplementation with refeeding differently affects up-regulation of muscle GS by
      fasting in vivo in adult female rats than glutamine alone. METHODS: Muscle GS
      activities were assessed in 5-day-fasted female Wistar adult rats refed and
      supplemented with glutamine or glycine in the presence or not of glucose.
      RESULTS: After 5-day-fasting, the up-regulated GS activity was decreased whatever
      the type of amino acid supplementation (glutamine or glycine), whereas it was
      more decreased by supplementation with a mixture glutamine/glucose. In
      glycine/glucose supplemented rats, no effect of glucose supplementation was
      observed on GS activity. CONCLUSION: These results demonstrated that
      intramuscular glutamine was spared when glucose was added to glutamine
      supplementation in adult rats. Consequently, the role of glucose consisted in
      slowing down the glutamine synthesis. By contrast, glucose has no role when it
      was associated with glycine whose degradation does not produce energy.

PMID- 17499398
TI  - The effect of glutamine-enriched enteral nutrition on intestinal microflora in
      very low birth weight infants: a randomized controlled trial.
AB  - BACKGROUND & AIMS: In a previous study, we have found that glutamine
      supplementation decreased the infection rate in very low birth weight (VLBW)
      infants. In this study, we investigated whether this beneficial effect originated
      from increased number of bifidobacteria and lactobacilli in the intestinal
      microflora of these infants. METHODS: In a randomized controlled trial, VLBW
      infants (gestational age <32 weeks and/or birth weight <1500g) received enteral
      glutamine supplementation (0.3g/kg/day) or isonitrogenous placebo supplementation
      between d3 and d30 of life. Faecal microflora was determined by fluorescent in
      situ hybridization <48h, at d7, d14 and d30 of life. RESULTS: In 43/52 (glutamine
      group) and 43/50 (control group) infants, > or = 2 samples were analyzed.
      Baseline characteristics were not different between groups. The prevalence of
      bifidobacteria, lactobacilli, Escheria coIi, streptococci and clostridia was not
      different between groups (p>0.05). In both groups, colonization with
      bifidobacteria was delayed, whereas potentially pathogenic bacteria such as E.
      coli, appeared rapidly after birth. Antibiotic treatment decreased the prevalence
      of all faecal bacteria (p<0.05). CONCLUSIONS: Decreased infectious morbidity in
      VLBW infants that received glutamine supplementation was not associated with
      alterations in the prevalence of bifidobacteria, lactobacilli, E. coIi,
      streptococci and clostridia. In general, colonization with health-promoting
      bacteria was delayed, whereas potentially pathogenic bacteria appeared rapidly
      after birth. Antibiotic treatment delayed the bacterial colonization.

PMID- 17499399
TI  - A critical contribution of both CD28 and ICOS in the adjuvant activity of
      Neisseria meningitidis H44/76 LPS and lpxL1 LPS.
AB  - The development of novel vaccines against Neisseria meningitidis recently gained
      momentum by the generation of penta-acylated lpxL1 LPS which has similar adjuvant
      activity, but reduced endotoxic activity as compared to hexa-acylated wild type
      (H44/76) LPS. We investigated the costimulation requirements for the adjuvant
      activity of both forms of LPS by immunizing CD28-, ICOS- and B7.1/2/ICOS
      deficient mice. Both ICOS and CD28 appeared essential for optimal adjuvant
      activity of H44/76 LPS or lpxL1 LPS. Interestingly, ICOS-mediated costimulation
      predominates in the adjuvant activity of lpxL1 LPS, while both ICOS and CD28 are
      required for H44/76 LPS adjuvant activity.

PMID- 17499400
TI  - An ESAT-6:CFP10 DNA vaccine administered in conjunction with Mycobacterium bovis
      BCG confers protection to cattle challenged with virulent M. bovis.
AB  - The potency of genetic immunization observed in the mouse has demonstrated the
      utility of DNA vaccines to induce cell-mediated and humoral immune responses.
      However, it has been relatively difficult to generate comparable responses in non
      rodent species. The use of molecular adjuvants may increase the magnitude of
      these suboptimal responses. In this study, we demonstrate that the co
      administration of plasmid-encoded GM-CSF and CD80/CD86 with a novel ESAT-6:CFP10
      DNA vaccine against bovine tuberculosis enhances antigen-specific cell-mediated
      immune responses. ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA vaccinated animals exhibited
      significant (p<0.01) antigen-specific proliferative responses compared to other
      DNA vaccinates. Increased expression (p< or =0.05) of CD25 on PBMC from ESAT
      6:CFP10+GM-CSF+CD80/CD86 DNA vaccinates was associated with increased
      proliferation, as compared to control DNA vaccinates. Significant (p<0.05)
      numbers of ESAT-6:CFP10-specific IFN-gamma producing cells were evident from all
      ESAT-6:CFP10 DNA vaccinated animals compared to control DNA vaccinates. However,
      the greatest increase in IFN-gamma producing cells was from animals vaccinated
      with ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA. In a low-dose aerosol challenge trial,
      calves vaccinated as neonates with Mycobacterium bovis BCG and ESAT-6:CFP10+GM
      CSF+CD80/CD86 DNA exhibited decreased lesion severity in the lung and lung
      associated lymph nodes following viruluent M. bovis challenge compared to other
      vaccinated animals or non-vaccinated controls. These data suggest that a combined
      vaccine regimen of M. bovis BCG and a candidate ESAT-6:CFP10 DNA vaccine may
      offer greater protection against tuberculosis in cattle than vaccination with BCG
      alone.

PMID- 17499401
TI  - Intranasal cowpox virus infection of the mouse as a model for preclinical
      evaluation of smallpox vaccines.
AB  - The intranasal infection of mice with cowpox virus (CPXV) has been evaluated as a
      model for smallpox infection in man. Administration of a lethal dose of CPXV
      allowed time for development of T-cell responses but antibodies could not be
      detected before death occurred. In contrast, infection with a sublethal dose was
      associated with an early T-cell response followed by neutralising antibodies
      which correlated with virus clearance. Comparison of two first generation
      smallpox vaccines revealed no significant differences in terms of immunogenicity,
      protection and post-challenge virus clearance. These studies show that the
      CPXV/mouse model is valuable for the initial assessment of smallpox vaccines.

PMID- 17499402
TI  - Validity of self-reported influenza and pneumococcal vaccination status among a
      cohort of hospitalized elderly inpatients.
AB  - Use of self-reported vaccination status is commonplace in assessing vaccination
      coverage for public health programs and individuals, yet limited validity data
      exist. We compared self-report with provider records for pneumococcal (23vPPV)
      and influenza vaccine for 4887 subjects aged>or=65 years from two Australian
      hospitals. Self-reported influenza vaccination status had high sensitivity (98%),
      positive predictive value (PPV) (88%) and negative predictive value (NPV) (91%),
      but low specificity (56%). Self-reported 23vPPV (previous 5 years) had a
      sensitivity of 84%, specificity 77%, PPV 85% and NPV 76%. Clinicians can be
      reasonably confident of self-reported influenza vaccine status, and for positive
      self-report for 23vPPV in this setting. For program evaluation, self-reported
      influenza vaccination coverage among inpatients overestimates true coverage by
      about 10% versus 1% for 23vPPV. Self-report remains imperfect and whole-of-life
      immunisation registers a preferable goal.

PMID- 17499403
TI  - Rapid identification of an HLA-B*1501-restricted vaccinia peptide antigen.
AB  - We identified a modified vaccinia virus Ankara (MVA)-peptide recognized by T
      cells of a vaccinated patient, applying a modified expression-based procedure.
      CD8(+) T cells reactive with MVA were expanded from peripheral blood of a patient
      after MVA-vaccination. The restricting HLA-elements and the antigen were
      determined applying stably HLA-class I-transfected K562 cells that were either
      infected wit MVA or transfected with a panel of MVA open reading frames (ORF).
      The T cells recognized the ORF 28R (K7R) gene product in association with HLA
      B*1501 and the peptide-coding region was localized applying truncated in vitro
      transcribed mRNA. The 9-mer peptide encoded (ORF 28(25-33), SIIDLIDEY) was
      identified that was also recognized by ex vivo CD8(+) T cells from the patient
      and further healthy individuals.

PMID- 17499404
TI  - Chimeric tymovirus-like particles displaying foot-and-mouth disease virus non
      structural protein epitopes and its use for detection of FMDV-NSP antibodies.
AB  - Expression of Physalis mottle tymovirus (PhMV) coat protein (CP) in Escherichia
      coli (E. coli) was earlier shown to self-assemble into empty capsids that are
      nearly identical to the capsids formed in vivo. Aminoacid substitutions were made
      at the N-terminus of wild-type PhMV CP with single or tandem repeats of infection
      related B-cell epitopes of foot-and-mouth disease virus (FMDV) non-structural
      proteins (NSPs) 3B1, 3B2, 3AB, 3D and 3ABD of lengths 48, 66, 49, 51 and 55,
      respectively to produce chimeras pR-Ph-3B1, pR-Ph-3B2, pR-Ph- 3AB, pR-Ph-3D and
      pR-Ph-3ABD. Expression of these constructs in E. coli resulted in chimeric
      proteins which self-assembled into chimeric tymovirus-like particles (TVLPs), Ph
      3B1, Ph-3B2, Ph-3AB, Ph-3D and Ph-3ABD as determined by ultracentrifugation and
      electron microscopy. Ph-3B1, Ph-3B2, Ph-3AB and Ph-3ABD reacted with polyclonal
      anti-3AB antibodies in ELISA and electroblot immunoassay, while wild-type PhMV
      TVLP and Ph-3D antigens did not react. An indirect ELISA (I-ELISA) was developed
      using Ph-3AB to detect FMDV-NSP antibodies in sera of animals that showed
      clinical signs of FMD. Field serum samples from cattle, buffalos, sheep, goats
      and pigs were examined by using these chimeric TVLPs for the differentiation of
      FMDV infected animals from vaccinated animals (DIVA). The assay was demonstrated
      to be highly specific (100%) and reproducible with sensitivity levels (94%)
      comparable to the Ceditest kit (P>0.05).

PMID- 17499405
TI  - Human receptors of innate immunity (CD14, TLR2) are promising targets for novel
      recombinant immunoglobulin-based vaccine candidates.
AB  - Experiments in mice have suggested that engagement of receptors of innate
      immunity has an adjuvant effect on adaptive immune responses. Such studies need
      to be extended to humans. We have here constructed recombinant scFv-based vaccine
      candidate proteins (vaccibodies) that target human TLR2 and CD14 for delivery of
      large antigens. Vaccibodies are homodimers, each chain consisting of scFv
      specific for surface molecules on antigen-presenting cells (APC), a
      homodimerization motif, and an antigenic unit. The TLR2- and CD14-specific
      vaccibodies bound their respective target receptors expressed on transfected CHO
      cells and PBMC. Large proteins such as paired mouse Ckappa-domains (229 aa) and
      fragment C of tetanus toxin (TetC, 451 aa) could be expressed as antigenic units
      with intact serological determinants detected by mAb or polyclonal antisera. In
      the presence of monocytes, TLR2- and CD14-specific vaccibodies having either
      Ckappa or TetC as antigenic unit were 100-10,000 more efficient at stimulating T
      cell clones in vitro compared to non-targeted vaccibodies expressing the same
      antigens. The results show that TLR2 and CD14 are efficient targets for delivery
      of antigen to APC for stimulation of HLA class II-restricted CD4(+) T cells.
      Thus, receptors of innate immunity should be further explored as targets for
      vaccines.

PMID- 17499406
TI  - Induction of immune memory following administration of a prophylactic
      quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle
      (VLP) vaccine.
AB  - BACKGROUND: The duration of protection afforded by vaccines represents a critical
      test of their utility as public health interventions. Some vaccines induce long
      term immunity, while others require booster doses. Vaccines that induce long-term
      protection are usually characterized by the generation of immune memory. Recent
      trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine
      have demonstrated high efficacy through 5 years of follow-up. We evaluated the
      extent to which the vaccine is able to generate HPV type-specific immune memory.
      METHODS: A total of 552, 16-23-year-old women were enrolled in a double-blind,
      placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio
      to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3
      years' follow-up. A subset of 241 subjects (n=114 in the quadrivalent HPV vaccine
      group and n=127 in the placebo group) underwent 2 further years of follow-up. All
      extension subjects received quadrivalent HPV vaccine at month 60 to examine the
      extent of immune memory in response to the primary vaccination series. RESULTS:
      Serum anti-HPV levels declined post-vaccination, but reached a plateau at month
      24 that remained stable through month 60. Administration of a challenge dose of
      vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post
      challenge reaching levels observed 1 month following the completion of the three
      dose primary series. At 1 month post-challenge, anti-HPV responses were higher
      than those observed 1-month post-dose 3. DISCUSSION: A three-dose regimen of
      quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at
      least 5 years. Vaccination also induces robust immune memory. These findings
      suggest that the efficacy of this vaccine will be long lasting.

PMID- 17499407
TI  - Patellar tendon load in different types of eccentric squats.
AB  - BACKGROUND: Differences in mechanical loading of the patellar tendon have been
      suggested as a reason for varying effects in rehabilitation of patellar
      tendinopathy using different eccentric squat exercises and devices. The aim was
      to characterize the magnitude and pattern of mechanical load at the knee and on
      the patellar tendon during four types of eccentric squat. METHODS: Subjects
      performed squats with a submaximal free weight and with maximal effort in a
      device for eccentric overloading (Bromsman), on a decline board and horizontal
      surface. Kinematics was recorded with a motion-capture system, reaction forces
      with force plates, and electromyography from three leg muscles with surface
      electrodes. Inverse dynamics was used to calculate knee joint kinetics. FINDINGS:
      Eccentric work, mean and peak patellar tendon force, and angle at peak force were
      greater (25-30%) for squats on decline board compared to horizontal surface with
      free weight, but not in Bromsman. Higher knee load forces (60-80%), but not work,
      were observed with Bromsman than free weight. Angular excursions at the knee and
      ankle were larger with decline board, particularly with free weight, and smaller
      in Bromsman than with free weight. Mean electromyography was greater on a decline
      board for gastrocnemius (13%) and vastus medialis (6%) with free weight, but in
      Bromsman only for gastrocnemius (7%). INTERPRETATION: The results demonstrated
      clear differences in the biomechanical loading on the knee during different squat
      exercises. Quantification of such differences provides information that could be
      used to explain differences in rehabilitation effects as well as in designing
      more optimal rehabilitation exercises for patellar tendinopathy.

PMID- 17499408
TI  - Quantitative ultrasound predicts bone mineral density and failure load in human
      lumbar vertebrae.
AB  - BACKGROUND: Quantitative ultrasound is in widespread clinical use for assessment
      of bone quality at peripheral skeletal sites, but has not yet been applied to
      those sites in the axial skeleton, such as the spine and hip, where osteoporotic
      fractures are common. METHODS: Ultrasound measurements were made in 11 cadaveric
      vertebrae and relationships with bone mineral density and failure load were
      investigated. An ultrasonic imaging system was used to measure speed of sound,
      broadband ultrasonic attenuation, and attenuation at a single frequency, through
      the vertebral body in the sagittal plane. Ultrasonic measurements were averaged
      over a region of interest centrally within the vertebral body, and were
      calculated with and without normalization for bone size. Vertebral bone mineral
      density was measured in antero-posterior and lateral projections using dual
      energy X-ray absorptiometry. Compressive mechanical testing was performed to
      determine vertebral failure load. FINDINGS: Bone mineral density correlated with
      failure load (r=0.74-0.78, all P<0.01), and with quantitative ultrasound (r=0.63
      0.82, P=0.038-0.004), in line with previous studies. Of the ultrasonic
      measurements, those parameters not normalized for bone size gave the highest
      correlations with failure load, ranging from r=0.71 (P=0.021) for speed of sound
      to r=0.93 (P<0.001) for attenuation. When ultrasonic measurements were normalized
      for bone size, the correlations with both failure load and bone mineral density
      were lower. INTERPRETATION: These results confirm the feasibility of vertebral
      quantitative ultrasound in vitro, and indicate that ultrasound does provide
      information on both bone mineral density and failure load. The predictive
      performance of ultrasonic measurements for failure load was comparable to or
      greater than that of bone mineral density, suggesting that ultrasound has the
      potential to be at least as useful as mineral density in the assessment of
      vertebral bone. Normalizing ultrasonic measurements for bone size reduced the
      strength of correlations because both bone mineral density and bone strength
      reflect bone size to a certain extent.

PMID- 17499409
TI  - Concentrations and characteristics of organochlorine pesticides in aquatic biota
      from Qiantang River in China.
AB  - The Qiantang River is a typical river flowing through an agricultural area in
      China. It was studied in 2006 for its aquatic biota quality by determining 13
      organochlorine pesticides (OCPs) in the edible parts of crabs, clams, shrimp,
      fish, aquatic plants, as well as water and sediments collected from seven sites
      along its upper reaches all the way downstream. The levels of all insecticides
      were in the range of 17+/-13 (water plants), 35+/-36 (shrimp), 32+/-14 (crabs),
      39+/-21 (clams), 47+/-35 (fish) ng/g wet weight (ww) and in the range of 2936+/
      2356 (water plants), 5827+/-6013 (shrimp), 2102+/-966 (crabs), 1859+/-1018
      (clams), 3624+/-11331 (fish) ng/g lipid. DDT and its metabolites were the
      predominant contaminants in most biota. A linear relationship was observed
      between the log bio-concentration factor (BCF) and log octanol-water partition
      coefficients (Kow) for fish, clams and shrimp. Composition analyses in various
      environmental media indicated a recent usage of lindane and dicofol into the
      river.

PMID- 17499410
TI  - WTP and WTA: do people think differently?
AB  - Contingent valuation (CV) studies in health care have used the willingness to pay
      (WTP) approach, to the virtual exclusion of willingness to accept (WTA). Outside
      the health care field, disparities between WTP and WTA values have been observed.
      Were such disparities to be demonstrated for health care technologies, the
      conventional assumption of a linear cost-effectiveness plane would be
      invalidated. This paper employs data derived from interviews with users of the
      UK's paediatric cochlear implantation (PCI) programme based in Nottingham (i) to
      assess the feasibility of estimating WTA for the potential discontinuation of an
      existing technology, and (ii) to investigate any WTA-WTP disparity which might be
      revealed. Only one-third of subjects providing WTP values were willing and able
      to offer a corresponding WTA value. Our qualitative data revealed that modes of
      response differed between the two valuation approaches. In particular, the
      presumption of fungibility of the health care intervention was a far more serious
      obstacle to completing the WTA task than it was for WTP. Among those prepared to
      offer values under both approaches, mean WTA was approximately four times mean
      WTP. Until more health studies are conducted, it remains unclear whether or not
      the findings are specific both to the intervention and to the elicitation format.

PMID- 17499411
TI  - Individual and neighborhood socioeconomic status and progressive chronic kidney
      disease in an elderly population: The Cardiovascular Health Study.
AB  - Few studies have focused on the association between socioeconomic status (SES)
      and progressive chronic kidney disease (pCKD) in an elderly population. We
      conducted a cohort study of 4735 Cardiovascular Health Study participants, ages
      65 and older and living in 4 US communities, to examine the independent risk of
      pCKD associated with income, education and living in a low SES area. pCKD was
      defined as creatinine elevation 0.4 mg/dL (35 micromol/L) over a 4-7 year follow
      up or CKD hospitalization. Area SES was characterized using measures of income,
      wealth, education and occupation for 1990 (corresponding to time of enrollment)
      US Census block groups of residence. Age and study site-adjusted incidence rates
      (per 1000 person years) of pCKD by quartiles of area-level SES score, income and
      education showed decreasing rates with increasing SES. Cox proportional hazards
      models showed that living in the lowest SES area quartile, as opposed to the
      highest, was associated with 50% greater risk of pCKD, after adjusting for age,
      gender, study site, baseline creatinine, and individual-level SES. This increased
      risk and trend persisted after adjusting for lifestyle risk factors, diabetes and
      hypertension. We found no significant independent associations between pCKD and
      individual-level income or education (after adjusting for all other SES factors).
      As such, living in a low SES area is associated with greater risk of pCKD in an
      elderly US population.

PMID- 17499412
TI  - Domain specific attentional impairments in children with chromosome 22q11.2
      deletion syndrome.
AB  - One of the defining cognitive characteristics of the chromosome 22q deletion
      syndrome (DS22q11.2) is visuospatial processing impairments. The purpose of this
      study was to investigate and extend the specific attentional profile of children
      with this disorder using both an object-based attention task and an inhibition of
      return task. A group of children with the disorder was compared in these tasks
      with a group of age-matched typically developing children. The children with
      DS22q11.2 demonstrated impaired spatially based orienting which is consistent
      with previous findings in this group. Strikingly, the children with DS22q11.2
      also demonstrated an improved ability to use object-based cues, relative to the
      typically developing group. Finally, the children with DS22q11.2 demonstrated an
      intact inhibition of return system, however, it appears to be delayed
      developmentally.

PMID- 17499413
TI  - Renin-angiotensin-system gene polymorphisms and depression.
AB  - Given the abundance of the renin-angiotensin system (RAS) components in the
      brain, their importance in behavior and cognition, and the data that implicates
      them in the etiology and treatment of depression, it is possible that those RAS
      gene polymorphisms associated with increased RAS activity may also be associated
      with depression. The frequencies of common polymorphisms of genes encoding for
      components of the RAS, namely angiotensinogen (M235T), angiotensin converting
      enzyme (ACE) (insertion, I; deletion, D), angiotensin receptor type I (A1166C),
      and angiotensin receptor type II (C3123A) were determined in DNA extracted from
      buccal cells from a Lebanese population of 132 depressed patients and their first
      degree relative case-controls. The angiotensin receptor type 1 (A1166C) CC
      genotype was significantly associated with depression (p=0.036). None of the
      other common RAS-associated polymorphisms were significantly associated. The
      results support the hypothesis that increased RAS activity may increase relative
      risk of depression in that the angiotensin receptor type 1 (A1166C) CC genotype
      is associated with increased responsiveness to angiotensin II.

PMID- 17499414
TI  - Acute and subchronic copper treatments alter extracellular nucleotide hydrolysis
      in zebrafish brain membranes.
AB  - Copper is a divalent cation with physiological importance since deficiency of
      copper homeostasis can cause serious neurological diseases. ATP is an important
      signalling molecule stored at nerve endings and its inactivation is promoted by
      ecto-nucleotidases. In this study, we verified the effect of acute and subchronic
      copper treatments on ecto-nucleotidase activities in zebrafish brain membranes.
      Treatment with copper sulfate (15 microg/L) during 24h inhibited ATP hydrolysis
      (16%), whereas ADP and AMP hydrolysis were not altered. Nevertheless, a 96-h
      exposure with the copper concentration mentioned above inhibited NTPDase (31% and
      42% for ATP and ADP hydrolysis, respectively) and ecto-5'-nucleotidase (40%)
      activities. NTPDase1, NTPDase2_mg and NTPDase2_mv transcripts were decreased
      after copper exposures during 24 and 96 h. Subchronic copper treatment also
      reduced the NTPDase2_mq and ecto-5'-nucleotidase expression. In vitro assays
      demonstrated that NTPDase activities were reduced after copper exposure during 40
      min. ATP hydrolysis was inhibited at 0.25, 0.5 and 1mM (13%, 31% and 48%,
      respectively) and ADP hydrolysis also had a significant decrease at these same
      copper concentrations (41%, 63% and 68%, respectively). In contrast to the
      subchronic exposure, no significant changes on ecto-5'-nucleotidase were observed
      after in vitro assays. Lineweaver-Burk plots suggested that both inhibitory
      effects on nucleotide hydrolysis may occur in a non-competitive manner.
      Altogether, these findings indicate that copper is able to promote distinct
      changes on ecto-nucleotidases after in vivo and in vitro treatments and,
      consequently, it could control the nucleotide and nucleoside levels, modulating
      the purinergic signalling.

PMID- 17499416
TI  - Urinary metabolites of diisodecyl phthalate in rats.
AB  - Diisodecyl phthalate (DiDP) is an isomeric mixture of phthalates with
      predominantly 10-carbon branched-dialkyl chains, widely used as a plasticizer for
      polyvinyl chloride. The extent of human exposure to DiDP is unknown in part
      because adequate biomarkers of exposure to DiDP are not available. We identified
      several major metabolites of DiDP in urine of adult female Sprague-Dawley rats
      after a single oral administration of DiDP (300 mg/kg). These metabolites can
      potentially be used as biomarkers of exposure to DiDP. The metabolites extracted
      from urine were chromatographically resolved and identified by their
      chromatographic behavior and full scan negative ion electrospray ionization mass
      spectrum. The identity of metabolites with similar molecular weights was further
      examined in accurate mass mode. For some metabolites, unequivocal identification
      was done using authentic standards. Among these were the hydrolytic monoester of
      DiDP, monoisodecyl phthalate (MiDP), detected as a minor metabolite, and one
      omega oxidation product of MiDP, mono(carboxy-isononyl) phthalate (MCiNP), which
      was the most abundant urinary metabolite. We also tentatively identified other
      secondary metabolites of MiDP, mono(hydroxy-isodecyl) phthalate, mono(oxo
      isodecyl) phthalate, mono(carboxy-isoheptyl) phthalate, mono(carboxy-isohexyl)
      phthalate, mono(carboxy-isopentyl) phthalate, mono(carboxy-isobutyl) phthalate,
      and mono(carboxy-ethyl) phthalate. Oxidative metabolites of diisoundecyl
      phthalate (DiUdP) and diisononyl phthalate (DiNP) were also detected suggesting
      the presence of DiUdP and DiNP in the DiDP formulation. The urinary
      concentrations of all these metabolites gradually decreased in the 4 days
      following the administration of DiDP. MCiNP and other DiDP secondary metabolites
      are more abundant in urine than MiDP, suggesting that these oxidative products
      are better biomarkers for DiDP exposure assessment than MiDP. Additional research
      on the toxicokinetics of these metabolites is needed to understand the extent of
      human exposure to DiDP from the urinary concentrations of MCiNP and other DiDP
      secondary metabolites.

PMID- 17499415
TI  - Low cadmium exposure triggers a biphasic oxidative stress response in mice
      kidneys.
AB  - Oxidative stress is believed to participate in the early processes of cadmium
      (Cd)-induced proximal tubular kidney damage. Mice were chronically exposed up to
      23 weeks to low Cd concentrations (10 and 100 mg CdCl(2)/l) via the drinking
      water. Pro- and antioxidant gene expression levels, glutathione, ascorbate and
      lipid peroxidation levels were measured. Our study provided evidence for an early
      and a late stress response in the kidney. Metallothioneins were upregulated from
      1 week of exposure on and they stayed important during the whole exposure period.
      After 8 weeks the expression of Bcl2 (anti-apoptotic), Prdx2 and cytosolic
      superoxide dismutase (Sod1) was reduced in the group exposed to 100 mg CdCl(2)/l,
      which might indicate a response to Cd-stress. However glutathione, ascorbate and
      lipid peroxidation levels did not significantly change, and the overall redox
      balance remained stable. Stable Sod2 transcriptional levels suggested that an
      increased formation of superoxide anions, which can arise upon Cd-induced
      mitochondrial free radical generation, was not appearing. A second defence
      activation was observed after 23 weeks: i.e. an increase of catalase (Cat),
      glutathione peroxidase 4 (Gpx4) and heme oxygenase 1 (Hmox1), together with NADPH
      oxidase 4 (Nox4), of which the role has not been studied yet in Cd
      nephrotoxicity. These findings were in contrast with previous studies, where Cd
      induced oxidative stress was detrimental when high Cd concentrations were
      applied. In conclusion our study provided evidence that a chronic exposure to low
      Cd concentrations triggered a biphasic defence activation in the kidney that
      might lead to adaptation and survival.

PMID- 17499417
TI  - Outcome of 12 drowned children with attempted resuscitation on cardiopulmonary
      bypass: an analysis of variables based on the "Utstein Style for Drowning".
AB  - BACKGROUND: In 2003, the International Liaison Committee on Resuscitation (ILCOR)
      published the "Utstein Style for Drowning" (USFD) to advance knowledge on the
      epidemiology, treatment, and outcome prediction after drowning. Applying the USFD
      and evaluating its data template for outcome analysis, we report here on the
      largest study published thus far of drowned children (age 0-14) who underwent
      attempted resuscitation on cardiopulmonary bypass (CPB). METHODS: We conducted a
      retrospective review of all drowned children admitted to Gottingen University
      Hospital between 1/1987 and 12/2005 in sustained cardiopulmonary arrest and
      resuscitation with CPB. We correlated eight outcome-affecting USFD variables and
      four additional variables not included in the USFD with potential impact on
      outcome to four outcome groups: survival, non-survival, survival with full
      recovery, and failed resuscitation. RESULTS: Out of 12 children (aged 22 months
      to 7.5 years), 5 survived to hospital discharge and 7 died in hospital. Two
      survivors recovered fully and three remained in a vegetative state. In two
      patients, resuscitation on CPB failed. Both children who fully recovered,
      compared to the 10 others, had relatively low serum K+ concentrations (2.6 and
      3.7 mmol/l versus 5.8+/-3.8 mmol/l [mean+/-S.D.; n=10]), a relatively slow
      rewarming speed (1.9 and 1.2 degrees C/h versus 3.4+/-1.8 degrees C/h), were
      female (all three girls survived), received early basic life support (BLS) and
      showed idioventricular bradycardia. Both children with failed resuscitation had
      severe hyperkalaemia (11.7 and 13.3 mmol/l versus 10 others, 4.0+/-1.5 mmol/l),
      were relatively rapidly rewarmed (6.9 and 4.0 degrees C/h versus 10 others,
      2.61+/-1.32 degrees C/h), male, and in asystole. We identified no outcome trends
      for age, pH, or water and core temperatures. CONCLUSIONS: Most variables relevant
      for outcome in drowned children can be documented with the use of the USFD.
      Additional variables not included in the USFD that have emerged from this study
      and may predict outcome include serum K+ concentration, rewarming speed, and
      initial cardiac rhythm.

PMID- 17499419
TI  - Intravenous tranexamic acid use in myomectomy: a prospective randomized double
      blind placebo controlled study.
AB  - OBJECTIVE: To define the effect of tranexamic acid use on perioperative and
      postoperative bleeding and blood transfusion requirements in women undergoing
      myomectomy. STUDY DESIGN: Among the patients that underwent myomectomy a total of
      100 cases were included in the study. The patients (n=50) randomized to receive
      tranexamic acid were defined as Group I and those receiving saline were defined
      as Group II. Perioperative blood loss was calculated by measuring the volume in
      the suction apparatus and weighing the swabs. Postoperative blood loss was
      defined as the blood volume found in the subfascial suction drain. The two groups
      were compared for age, body mass index, basal hemoglobin and hematocrit, basal
      parameters of coagulation, the number and the volume of myomas removed, peri- and
      postoperative and total blood loss, duration of surgery and blood transfusion
      requirements. RESULTS: No significant difference was found between the two groups
      when compared age, body mass index, preoperative blood analysis, the number and
      volume of myomas removed. Statistically significant differences were found
      between the two groups when compared for postoperative and total blood loss and
      duration of surgery (p<0.01, p=0.03 and p=0.03, respectively). Perioperative
      blood loss and blood transfusion requirements were similar between the two groups
      (p=0.12 and p=0.25, respectively). There were no complications in either group.
      CONCLUSION: Our study is the first in the literature evaluating the effectiveness
      of tranexamic acid use on peri- and postoperative bleeding in gynecological
      surgery. No additional benefit of intravenous infusion of tranexamic acid was
      found. Tranexamic acid does not seem to be a useful adjunct in myomectomy if
      given according to the described protocol in this study.

PMID- 17499418
TI  - Pain experience during chorionic villus sampling and amniocentesis: a preliminary
      study.
AB  - OBJECTIVE: To investigate the maternal perception of pain before and after
      amniocentesis (AC) or transabdominal chorionic villus sampling (TA-CVS). STUDY
      DESIGN: Three hundred women were divided into groups of 100 participants destined
      to undergo three different fetal sampling procedures: amniocentesis (group 1),
      transabdominal chorionic villus sampling (CVS) with a 19 gauge Blache needle
      (group 2) and transabdominal CVS with a 20 gauge needle (group 3). The visual
      analog scale (VAS) was used to quantify the patient's pre-sampling expected pain
      level and the real pain level was measured immediately after the sampling
      procedure. The factors liable to influence the VAS score after the sampling
      procedure were studied by single and multivariate analysis and concerned either
      the sampling procedure or patient demographic data. RESULTS: The VAS scores
      obtained before the procedure were not significantly different for the three
      sampling groups. When performed with a 19 gauge Blache needle TA-CVS is
      significantly more painful than the other sampling procedures (p=0.0002): VAS
      score of 3.62 (group 2), 2.49 (group 3) and 2.68 (group 1) for CVS with 20 gauge
      needle and amniocentesis. Multivariate analysis identified a group of patients
      for which the perception of pain induced by sampling was higher compared to the
      other patients: nulliparous patients, having undergone 19 gauge Blache needle
      CVS, with a high pre-sampling VAS score. CONCLUSION: Transabdominal chorionic
      villus sampling with a 19 gauge Blache needle seems to be the most painful
      sampling procedure. We question the need to use a 19 gauge needle as acceptable
      results are obtained with a 20 gauge needle.

PMID- 17499420
TI  - The impact of human frequentation on coastal vegetation in a biosphere reserve.
AB  - We aimed to assess the impacts of recreational trampling on rare species, plant
      communities and landscape structure in the Iroise Biosphere Reserve (western
      France). Focusing on coastal grasslands, we first identified indicators
      discriminating human-induced short grasslands (i.e. maintained short by intensive
      trampling) from natural short grasslands (i.e. maintained by environmental
      constraints): the presence of lichens and succulent or woody species, which are
      known to be highly sensitive to trampling, as well as a shallow soil were good
      indicators of natural short grasslands. Recreational activities affected the
      majority of plots containing rare species, but one third of rare species
      (according to their habitat preference) appeared currently not threatened by
      recreational activities. The other rare species were found in grasslands with low
      trampling intensity and were not found in grasslands with greater trampling
      intensity. One lichen species (Teloshistes flavicans) was not affected by
      trampling intensity, while two plants species (Scilla verna and Ophioglossum
      lusitanicum) showed higher abundances when trampling was low to medium. When it
      occurs in natural short grasslands, tourist trampling reduced drastically plant
      species richness. However, when considering maritime high grasslands, we observed
      that species richness was higher under low trampling vs. no trampling, but
      decreased at higher trampling intensity. At a landscape scale, the mean annual
      rate of path creation was about 1.6% and tourist trampling has already completely
      destroyed 3.5 ha of natural coastal vegetation. Trampling of maritime-high
      grassland has also created 31 ha of short grasslands, which represent 50.8% of
      the whole short grassland habitat of the island. Moreover trampling affected
      respectively, 41% and 15% of natural short grasslands and maritime-high
      grasslands. One of the main suggestions for managers to minimise trampling
      impacts should be to protect areas of rocky soil covered by short grassland that
      are still non-trampled and not impacted. Fortunately, this appears compatible
      with a relatively free access of visitors to coastal areas, as tourists can be
      redirected towards maritime-high grasslands, an habitat which is less impacted by
      tourism in terms of affected surface, soil cover, loss of species, or presence of
      rare species host.

PMID- 17499421
TI  - Fuzzy pricing for urban water resources: model construction and application.
AB  - A rational water price system plays a crucial role in the optimal allocation of
      water resources. In this paper, a fuzzy pricing model for urban water resources
      is presented, which consists of a multi-criteria fuzzy evaluation model and a
      water resources price (WRP) computation model. Various factors affecting WRP are
      comprehensively evaluated with multiple levels and objectives in the multi
      criteria fuzzy evaluation model, while the price vectors of water resources are
      constructed in the WRP computation model according to the definition of the
      bearing water price index, and then WRP is calculated. With the incorporation of
      an operator's knowledge, it considers iterative weights and subjective preference
      of operators for weight-assessment. The weights determined are more rational and
      the evaluation results are more realistic. Particularly, dual water supply is
      considered in the study. Different prices being fixed for water resources with
      different qualities conforms to the law of water resources value (WRV) itself. A
      high-quality groundwater price computation model is also proposed to provide
      optimal water allocation and to meet higher living standards. The developed model
      is applied in Jinan for evaluating its validity. The method presented in this
      paper offers some new directions in the research of WRP.

PMID- 17499422
TI  - Hydrochemical evaluation of the Voltaian system--the Afram Plains area, Ghana.
AB  - Inverse geochemical modeling from PHREEQC, and multivariate statistical methods
      were jointly used to define the genetic origin of chemical parameters of
      groundwater from the Voltaian aquifers in the Afram Plains area. The study finds,
      from hierarchical cluster analysis that there are two main hydrochemical facies
      namely the calcium-sodium-chloride-bicarbonate waters and the magnesium-potassium
      sulfate-nitrate waters in the northern and southern sections, respectively, of
      the Afram Plains area. This facies differentiation is confirmed by the
      distribution of the SO(4)(2-)/Cl(-) ratio, which associates groundwater from the
      northern and southern sections to areas influenced by contact with evaporites and
      seawater, respectively. Principal component analysis (PCA) with varimax rotation
      using the Kaiser criterion identifies four principal sources of variation in the
      hydrochemistry. Mineral saturation indices calculated from both major ions and
      trace elements, indicate saturation-supersaturation with respect to calcite,
      aragonite, k-mica, chlorite, rhodochrosite, kaolinite, sepiolite, and talc, and
      undersaturation with respect to albite, anorthite, and gypsum in the area.
      Inverse geochemical modeling along groundwater flowpaths indicates the
      dissolution of albite, anorthite and gypsum and the precipitation of kaolinite, k
      mica, talc, and quartz. Both the PCA and inverse geochemical modeling identify
      the incongruent weathering of feldspars as the principal factors controlling the
      hydrochemistry in the Afram Plains area. General phase transfer equations have
      been developed to characterize the geochemical evolution of groundwater in the
      area. A very good relationship has been established between calcite and aragonite
      saturation indices in the Afram Plains area, with R(2)=1.00.

PMID- 17499423
TI  - Immobilization of Pb(II), Cd(II) and Ni(II) ions on kaolinite and montmorillonite
      surfaces from aqueous medium.
AB  - The present study investigates the immobilization of Pb(II), Cd(II) and Ni(II) on
      clays (kaolinite and montmorillonite) in aqueous medium through the process of
      adsorption under a set of variables (concentration of metal ion, amount of clay,
      pH, time and temperature of interaction). Increasing pH favours the removal of
      metal ions till they are precipitated as the insoluble hydroxides. The uptake is
      rapid with maximum adsorption being observed within 180 min for Pb(II) and Ni(II)
      and 240 min for Cd(II). A number of available models like the Lagergren pseudo
      first-order kinetics, second-order kinetics, Elovich equation, liquid film
      diffusion and intra-particle diffusion are utilized to evaluate the kinetics and
      the mechanism of the immobilization interactions. Two isotherm equations due to
      Langmuir and Freundlich showed good fits with the experimental data. Kaolinite
      and montmorillonite have considerable Langmuir monolayer capacity with respect to
      Pb(II), Cd(II) and Ni(II), the values being in the range of 6.8-11.5mg/g
      (kaolinite) and 21.1-31.1mg/g (montmorillonite). The Freundlich adsorption
      capacity follows a similar order. The thermodynamics of the immobilization
      process indicates the same to be exothermic with Pb(II) and Ni(II), but
      endothermic with Cd(II). The interactions with Pb(II) and Ni(II) are accompanied
      by decrease in entropy and Gibbs energy while the endothermic immobilization of
      Cd(II) is supported by an increase in entropy and an appreciable decrease in
      Gibbs energy. The results have established good potentiality for kaolinite and
      montmorillonite to remove heavy metals like Pb(II), Cd(II) and Ni(II) from
      aqueous medium through adsorption-mediated immobilization.

PMID- 17499424
TI  - At what point does warm ischemia cause permanent renal damage during partial
      nephrectomy?

PMID- 17499425
TI  - hK2 and free PSA, a prognostic combination in predicting minimal prostate cancer
      in screen-detected men within the PSA range 4-10 ng/ml.
AB  - OBJECTIVES: The purpose of screening for prostate cancer is to decrease the
      disease-specific mortality. However not every screen-detected prostate cancer is
      a threat to the patient's life. The risk of overdetection and subsequent
      overtreatment in prostate cancer has been recognised. The purpose of this
      investigation was to evaluate the role of tumour markers total PSA, free PSA, and
      hK2, and their combinations in predicting minimal prostate cancer. METHODS:
      Within the European Randomized Study of Screening for Prostate Cancer (ERSPC),
      section Rotterdam, The Netherlands, prebiopsy serum samples were analysed for 100
      selected men who underwent a radical prostatectomy for their screen-detected
      prostate cancer. All had a PSA value between 4 and 10 ng/ml prior to diagnosis.
      Minimal prostate cancer is defined as organ confined, Gleason score </=6 (no
      Gleason grade 4 or 5), and tumour volume <0.5 ml. RESULTS: Sera and tumour
      volumes from 91 men were available for analysis. Minimal prostate cancer was
      diagnosed in 16.5% of the selected cases. Mean tumour volume was 1.2 ml (range:
      0.04-13.5); hK2, the algorithms hK2/fPSA, and hK2/%fPSA have significant
      correlations with tumour volume. Both algorithms also yielded the best test
      results in predicting minimal disease with an area under the receiver operator
      characteristics curve of 82%. CONCLUSIONS: hK2 and percent free PSA have added
      prognostic value for the detection of minimal prostate cancer in screen-detected
      cases within PSA range 4-10 ng/ml. These biomarkers can possibly be used to
      select less invasive treatment options like active surveillance and to prevent
      overtreatment.

PMID- 17499426
TI  - Editorial comment on: Holmium laser enucleation versus transurethral resection of
      the prostate: 3-year follow-up results of a randomized clinical trial.

PMID- 17499427
TI  - Holmium laser enucleation versus transurethral resection of the prostate: 3-year
      follow-up results of a randomized clinical trial.
AB  - OBJECTIVES: To report 3-yr follow-up results of a randomised clinical trial
      comparing holmium laser enucleation of the prostate (HoLEP) with transurethral
      resection of the prostate (TURP). METHODS: A total of 200 patients with
      urodynamic obstruction and a prostate volume of less than 100 cc were
      prospectively randomised and assigned to HoLEP or TURP. All patients were
      assessed preoperatively and followed at 1, 6, 12, 18, 24, and 36 mo
      postoperatively. American Urological Association Symptom Score (AUA SS), maximum
      flow rate (Q(max)), and postvoid residual (PVR) [urine] volume were obtained at
      each follow-up. Perioperative data and postoperative outcome were compared. All
      complications were recorded. RESULTS: AUA SS were significantly better 2 yr
      postoperatively in the HoLEP group (1.7 vs. 3.9, p<0.0001) and similar at 3 yr
      (2.7 vs. 3.3, p=0.17). PVR volume was significantly better 2 yr (5.6 vs. 19.9 ml,
      p<0.001) and 3 yr (8.4 vs. 20.2 ml, p=0.012) postoperatively in HoLEP patients.
      Q(max) was similar in the HoLEP and TURP groups at 2 yr (28.0 vs. 29.1 ml/s,
      p=0.83) and at 3 yr (29.0 vs. 27.5 ml/s, p=0.41) postoperatively. Late
      complications consisted of urethral strictures, bladder-neck contractures, and
      BPH recurrence; reoperation rates were 7.2% in the HoLEP and 6.6% in the TURP
      group (p=1.0). CONCLUSIONS: After 2 and 3 yr of follow-up, HoLEP micturition
      outcomes compare favourably with TURP. Late complications are equally low. HoLEP
      may be a real alternative to TURP.

PMID- 17499428
TI  - Editorial comment on: Holmium laser enucleation versus transurethral resection of
      the prostate: 3-year follow-up results of a randomized clinical trial.

PMID- 17499429
TI  - Re: Hamid Mazdak, Iraj Meshki and Fatemeh Ghassami. Effect of mitomycin C on
      anterior urethral stricture recurrence after internal urethrotomy. Eur Urol
      2007;51:1089-92.

PMID- 17499430
TI  - Fascin over-expression is associated with aggressiveness of oral squamous cell
      carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is associated with a high potential of tumor
      recurrence and metastasis, leading to poor prognosis. Cell motility is an
      important factor in the progression and metastasis of cancers. Recently, Fascin
      has been linked to tumor progression by induction of cell motility. However, the
      precise roles of Fascin in OSCC have not been elucidated clearly. The aim of this
      study was to analyze the roles of Fascin in OSCC progression using OSCC clinical
      samples. We demonstrated that Fascin over-expression was found in OSCC clinical
      samples and its expression was significantly associated with nodal metastasis
      (p=0.027), tumor recurrence (p<0.001) and poor patients' overall survival
      (p=0.013). Consistently, Fascin proteins were detected in all OSCC cell lines
      with the expression level corresponding to the invasion ability. To specifically
      investigate the mechanism of Fascin in OSCC, we examined the E-cadherin
      expression in the same set of OSCC specimens. Fascin was negatively correlated
      with E-cadherin expression (p=0.018, r=-0.513). In conclusion, our findings
      suggested that Fascin over-expression might enhance OSCC aggressiveness, possibly
      by interacting with E-cadherin expression.

PMID- 17499431
TI  - Reduction of acidity and removal of metal ions from coal mining effluents using
      chitosan microspheres.
AB  - Effluents from coal mining operations are not only highly acid but also depict
      elevated concentrations of metals which may contaminate the environment. Due to
      the polybasic characteristic of chitosan, this biopolymer is capable of both
      neutralizing and removing iron, aluminum and copper ions from such effluents. The
      present study aimed at evaluating the use of chitosan microspheres for their
      importance in continuous systems. The microspheres were prepared by the phase
      inversion method. Their average diameter and morphology were determined. Water
      samples from decantation pool (DP) and acidic mine drainage (AMD) effluents were
      treated using different amounts of microspheres. The pH and concentration of Fe,
      Al and Cu ions were evaluated both before and after treatment of effluent
      samples. The results revealed that the microspheres were capable of increasing
      the pH of DP and AMD samples from 2.34 and 2.58, respectively, to 6.20, i.e.,
      close to neutrality. The treatment also resulted in full removal of the metals
      investigated.

PMID- 17499433
TI  - Degradation of PCDD/Fs by mechanochemical treatment of fly ash from medical waste
      incineration.
AB  - The potential of mechanochemical treatment (MC) to degrade PCDD/Fs contained in
      fly ash was tested via grounding with and without calcium oxide (CaO) under
      atmospheric pressure. Three types of fly ash collected from medical waste
      incineration were compared, originating either from rotary kiln fluidized bed
      multi-stage incinerator using activated carbon spray (FA1, FA2), or a simple
      stoker incinerator without activated carbon spray (FA3). In test I: CaO to FA1
      mixed at ratio of 6-60% was milled at rotational speed of 350 rpm; in test II:
      FA2 and FA3 without CaO were milled at rotational speed of 400 rpm. The duration
      of the tests was 2h. The results from the present study indicate that (1) under
      two test conditions of with and without CaO, PCDD/Fs contained in real fly ash
      both can be degraded by mechanochemical treatment, (2) under condition of
      blending with CaO, the degradation efficiency of PCDD/Fs increased with
      increasing ratio of CaO, (3) the degradation efficiency of PCDD/Fs may increase
      with rotational speed increasing and (4) the destruction and dechlorination are
      major mechanism for PCDD/Fs degradation. These results show that mechanochemical
      treatment is a high potential technology for PCDD/Fs degradation in fly ash.

PMID- 17499434
TI  - Biosorption of Reactive Red-120 dye from aqueous solution by native and modified
      fungus biomass preparations of Lentinus sajor-caju.
AB  - The capacities and mechanisms of native and treated white-rot fungus "Lentinus
      sajur-caju" biomass preparations in removing of textile dye (i.e. Reactive Red
      120) from aqueous solution was investigated with different parameters, such as
      adsorbent dosage, pH, temperature and ionic strength. In the batch system, the
      maximum dye uptake on all the tested fungal biomass preparations was observed at
      pH 3.0, and the dye uptake capacities of the biosorbents (at 800 mg/l dye
      concentration) were found to be 117.8, 182.9, 138.6 and 57.2mg/g for native and
      heat-, acid- and base-treated dry fungal preparations, respectively. The uptake
      capacities order of the fungal preparations for the dye were found as heat
      treated>acid-treated>native>base-treated. The Langmuir, Freundlih and Temkin
      adsorption models were used for the mathematical description of the biosorption
      equilibrium. The Freundlich and Temkin models were able to describe the
      biosorption equilibrium of Reactive Red-120 on the fungal biomass preparations.
      The dye biosorption on the fungal biomass preparations followed second-order
      kinetic model and equation.

PMID- 17499435
TI  - TG-DTA, DRIFT and NMR characterisation of humic-like fractions from olive wastes
      and amended soil.
AB  - The purpose of the present study is to investigate, by means of thermogravimetric
      analysis (TG) and differential thermal analysis (DTA), diffuse reflectance
      infrared Fourier transform (DRIFT) and 2D nuclear magnetic resonance (NMR)
      spectroscopies, the structural features of the humic-like fraction (HLF) from
      olive pulp (OP), its effluents originated from the fermentation processes for
      hydrogen (EH2) and methane production (ECH4) and humic acid (HA) from soil
      amended with each of these materials. A considerable structural modification
      emerged between the HLF, in particular from the ECH4 effluent, which was
      characterised by a high content of polyphenolic and polypeptidic substances. The
      short-term amendment trial with OP and EH2 indicated that no chemical or
      structural changes in soil HA appeared. In contrast, the amendment with ECH4
      substantially influenced the chemical and structural composition of soil HA. The
      structural interpretation performed by 2D NMR indicated the presence of aliphatic
      and aromatic protons while the sugar-like content and O-CH3 groups decreased with
      respect to the soil control HA. It emerges from this study that olive wastes
      contain stabilised humic-like material that may be recycled as an amendment in
      areas where olive trees are cultivated.

PMID- 17499437
TI  - Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic
      ischemic injury in developing brains.
AB  - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is up-regulated in
      oligodendrocytes (OLs) in mouse models for genetic neurological disorders
      including globoid cell leukodystrophy (twitcher) and GM1 and GM2 gangliosidoses
      and in the brain of patients with multiple sclerosis. Since L-PGDS-deficient
      twitcher mice undergo extensive neuronal death, we concluded that L-PGDS
      functions protectively against neuronal degeneration. In this study, we
      investigated whether L-PGDS is also up-regulated in acute and massive brain
      injury resulting from neonatal hypoxic-ischemic encephalopathy (HIE). Analysis of
      brains from human neonates who had died from HIE disclosed that the surviving
      neurons in the infarcted lesions expressed L-PGDS. Mouse models for neonatal HIE
      were made on postnatal day (PND) 7. Global infarction in the ipsilateral
      hemisphere was evident at 24h after reoxygenation in this model. Intense L-PGDS
      immunoreactivity was already observed at 10 min after reoxygenation in apparently
      normal neurons in the cortex, and thereafter, in neurons adjacent to the
      infarcted area. Quantitative RT-PCR revealed that the L-PGDS mRNA level of the
      infarcted hemisphere was 33-fold higher than that of the sham-operated mouse
      brains at 1h after reoxygenation and that it decreased to the normal level by 24h
      thereafter. Furthermore, in both human and mouse brains, many of L-PGDS-positive
      cells were also immunoreactive for p53; and some of these expressed cleaved
      caspase-3. The expression of L-PGDS in degenerating neurons implies that L-PGDS
      functions as an early stress protein to protect against neuronal death in the HIE
      brain.

PMID- 17499438
TI  - Dopaminergic differentiation of grafted GFP transgenic neuroepithelial stem cells
      in the brain of a rat model of Parkinson's disease.
AB  - Neuroepithelial stem cells (NEPs) possess multipotent potential for self-renewal
      and neuronal differentiation. Using green fluorescent protein (GFP) positive
      NEPs, we explored, firstly, the survival and differentiation of grafted NEPs in
      the host rat and, secondly, whether or not transplantation of NEPs is a feasible
      therapeutic option for treating Parkinson's disease. NEPs were harvested from the
      neural tube of enhanced GFP transgenic embryos. In culture, GFP(+) NEPs generated
      abundant neurospheres and differentiated into both neurons and glia. When
      stereotaxically transplanted into the 6-hydroxydopamine (6-OHDA)-lesioned
      striatum of rats, NEPs survived and tyrosine hydroxylase (TH)-positive cells were
      detected in the graft. Furthermore, these grafted GFP(+) NEPs significantly
      ameliorated Parkinsonian behavioral symptoms compared with controls which were
      treated only with normal saline. Our results suggest that transplanted NEPs
      accomplish dopaminergic differentiation may be used for treating Parkinson's
      disease.

PMID- 17499439
TI  - What do pressure pipes tell us about spatial summation in pain processing.

PMID- 17499440
TI  - Fertility issues in survivors from adolescent cancers.
AB  - Infertility is a common and distressing late-effect of cancer treatment. Whist
      sperm banking for post-pubertal males and embryo freezing for women (who are in a
      stable relationship at the time of treatment) are highly successful fertility
      preservation strategies, for females without a partner (including young and pre
      pubescent girls) and pre-pubescent boys (or azoospermic men), there remain no
      effective approaches. Whilst the biological effects of cancer treatments on the
      reproductive system are well described, there are few data on the relative
      incidence of infertility (failure to conceive after one year of trying) in cancer
      survivors. This makes it difficult to advise survivors about their future
      fertility prospects. Whilst some will undoubtedly conceive naturally with their
      partner, others will require assisted conception treatment of which in vitro
      fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) are the most
      common. Pregnancy outcomes of cancer survivors are generally good, although there
      is increased risk of pre-term birth and low birth-weight in the offspring of
      women who have received pelvic irradiation. There is no increased incidence of
      genetic disease or cancer incidence in the offspring of cancer survivors. Current
      research directions are focussing on alternative fertility preservation
      strategies including in vitro maturation techniques, xenotransplantation and the
      development of technology to create artificial gametes in the laboratory.
      Finally, although the reproductive techniques discussed are highly effective,
      country specific differences in the legal framework means that cancer survivors
      may be denied access to certain treatments (e.g. embryo cryopreservation) because
      they are forbidden by specific national legislation.

PMID- 17499441
TI  - Effects of different kinds of couple interaction on cortisol and heart rate
      responses to stress in women.
AB  - In animal studies, positive social interaction and physical contact play a
      preeminent role in the control of behavioral and neuroendocrine responses to
      stress. The aim of this study was to determine whether specific kinds of couple
      interaction reduce hypothalamic-pituitary-adrenal (HPA) and autonomic responses
      to psychosocial stress in women. Sixty-seven women, aged 20-37 years, who had
      been married or cohabiting with a male partner for at least 12 months at the time
      of the study, were exposed to a standardized psychosocial laboratory stressor
      (Trier Social Stress Test). Participants were randomly assigned to three study
      groups differing in the type of a 10-min period of social interaction with their
      partner prior to stress: n=25 with no partner interaction, n=22 with verbal
      social support, and n=20 with physical contact (standardized neck and shoulder
      massage). Salivary free cortisol levels, plasma levels of oxytocin, heart rate,
      and psychological responses to stress were compared among the three study groups.
      Women with positive physical partner contact before stress exhibited
      significantly lower cortisol and heart rate responses to stress but no different
      plasma oxytocin levels compared to women who received social support or no social
      interaction. Verbal social support alone was not associated with reduced stress
      responsiveness. Our results are in line with previous human studies indicating
      reduced responsiveness to verbal social support by a spouse in women. More
      importantly, these findings imply a direct protective effect of touch on stress
      related neurobiological systems as a possible underlying mechanism of health
      beneficial effects of positive couple interaction.

PMID- 17499442
TI  - Alcohol assessment using wireless handheld computers: a pilot study.
AB  - The present study sought to test the feasibility of measuring quantity and
      frequency of self-reported alcohol consumption among college students using the
      Handheld Assisted Network Diary (HAND) by comparing results to a retrospective
      Timeline Followback (TLFB). A total of 40 undergraduate college students
      completed a HAND assessment during the two-week study period and completed a TLFB
      at follow-up. The HAND recorded similar levels of alcohol consumption compared to
      the TLFB. There were no significant differences in overall alcohol consumption,
      drinks per drinking day, or heavy drinking days between the two methods of
      assessment. Handheld computers may represent a useful tool for assessing daily
      alcohol use among college students.

PMID- 17499443
TI  - Discrepancies between self-report and objective measures for stimulant drug use
      in HIV: cognitive, medication adherence and psychological correlates.
AB  - While it has long been recognized that self-reported drug use may be at variance
      with objectively obtained evidence such as urine toxicology assays, few studies
      have explored the behavioral correlates of such discrepancies. Here we compared
      self-reported and objective measures of stimulant drug use for 162 HIV infected
      individuals and identified a sub-group with discrepancies between data obtained
      via the two methods. Results showed poorer neurocognitive performance (attention,
      learning/memory) and lower medication adherence rates for the discrepant group as
      compared to those who either acknowledged their drug use or accurately denied
      recent stimulant use. Using the Millon Clinical Multiaxial Inventory-III, it was
      also found that those in the discrepant group were more hesitant to reveal
      psychopathology. Comparisons of self-reported and objectively measured medication
      adherence data are also discussed.

PMID- 17499444
TI  - Randomized controlled trial of physical activity counseling as an aid to smoking
      cessation: 12 month follow-up.
AB  - There is some evidence to suggest that regular supervised physical activity may
      be useful as an aid to smoking cessation. It is unclear whether less extensive
      interventions confer similar benefits. This study examined whether physical
      activity counseling alone increases long-term smoking abstinence and physical
      activity levels and reduces weight gain. 299 male and female smokers were
      randomized to a 7-week smoking cessation program, including nicotine replacement
      therapy, plus either (i) physical activity counseling ('exercise', N=154), or
      (ii) health education advice ('control', N=145). There was no significant
      difference in rates of continuous smoking abstinence between the exercise group
      and the controls at 12 months following the quit day (9.1% versus 12.4%).
      Significant increases in physical activity levels observed for the exercise group
      versus the controls at six weeks were not maintained at 12 months. There was a
      non-significant tendency for less weight gain in the exercise group versus the
      controls at 12 months (P=0.06). Further trials are needed to examine the effect
      of more extensive physical activity interventions on smoking cessation, physical
      activity levels and post-cessation weight gain.

PMID- 17499446
TI  - Prolonged stress will induce Alzheimer's disease in elderly people by increased
      release of homocysteic acid.
AB  - Recently, many papers have reported the physiological functions of amyloid beta
      and amyloid precursor protein (APP). In particular, one of its functions is of
      importance for synaptic plasticity. Extracellular amyloid beta may suppress
      synaptic plasticity or inhibit long-term potentiation (LTP) from outside the
      cell. LTP is now considered the molecular basis of memory. Amyloid beta may
      induce the inhibition or loss of memory. We propose that suppression of LTP by
      amyloid beta induces a kind of physiological forgetfulness. On the other hand,
      homocysteic acid (HA) which is released from astrocytes under stress conditions
      accumulates the amyloid beta into neuronal cell, which consequently induces the
      inhibition of amyloid beta physiological function and induces strong LTP. We
      propose that HA induces strong unforgetful memory under stress condition such as
      PTSD and emotional depression. The situation is different in the elderly people.
      Prolonged stress in the elderly people may induce neurodegenerative diseases such
      as Alzheimer's disease. We observed that in the presence of excess methionine, HA
      induced alpha-synuclein protein in cultured cells, suggesting a hypermethylation
      model in vivo. Usually hypermethylation is observed in the ageing process. We
      have shown that HA promotes the accumulation of amyloid beta in cells, and that
      the production of alpha-synuclein, which induces the aggregation of amyloid beta,
      impairing the cell function. LTP is inhibited by deficient cellular function,
      which means that memories cannot be formed. In fact, there is confusion of
      memories in the early stages of Alzheimer's disease. Finally, the aggregated
      alpha-synuclein induces tau pathology, which induces cell death, leading to
      Alzheimer's pathology. In conclusion, we propose that HA induces Alzheimer's
      pathology in the elderly people because of prolonged stress.

PMID- 17499445
TI  - Evaluating personal alcohol feedback as a selective prevention for college
      students with depressed mood.
AB  - OBJECTIVE: This research evaluated a brief mailed intervention for alcohol use as
      an adjunct to a brief treatment for college students with depression symptoms.
      The intervention aimed to correct normative misperceptions and reduce students'
      drinking and related consequences. METHOD: One hundred seventy seven college
      students (70% Female) with elevated scores on the Beck Depression Inventory were
      randomly assigned to intervention or control group. Participants in the
      intervention were mailed feedback and information detailing their reported
      alcohol use, moderation strategies, and accurate normative information regarding
      student drinking. RESULTS: Results indicated no main effects of the intervention
      on drinking or related problems but students receiving feedback showed
      significant reductions in their perception of drinking norms compared to the
      control group. Furthermore, students whose normative perceptions reduced showed
      significant reductions in total drinks per week and total alcohol related
      problems compared to those whose norms did not reduce. CONCLUSIONS: Results
      support the importance of correcting normative perceptions and provide direction
      for selective prevention of alcohol use and related problems among college
      students with depressed mood.

PMID- 17499447
TI  - Statins may be useful in diabetic foot ulceration treatment and prevention.
AB  - Diabetic foot ulcers (DFUs) consist of an interaction of neuropathy, ischemia and
      infection. Neuropathy affects sensory, motor and autonomic pathways. Pathogenic
      factors for neuropathy include hyperglycemia, nonenzymatic glycosylation,
      oxidative stress, ischemic and hypoxic factors, nerve growth factor anomalies,
      activation of polyol pathway and immunologic abnormalities. All these factors are
      stated to contribute to microvascular disease and neural dysfunction. Peripheral
      neuropathy and ischemia combined with repetitive traumas can lead to diabetic
      foot ulceration. Fifteen percent of diabetic patients develop foot ulcers during
      their lifetime and nonhealing ulcers are responsible for 85% of nontraumatic
      lower extremity amputation. On the other hand, the treatment cost of foot disease
      in diabetic patients is estimated at $1 billion annually. When these conditions
      are considered, it is very important to design improved and novel strategies for
      treatment and prevention of diabetic foot disease. Lipid-lowering agents, such as
      statins, have been shown to prevent cardiovascular events in patients with
      diabetes. However, in addition, to preventing macrovascular diseases, statins may
      also be able to retard the progression of microvascular complications of
      diabetes. Statins alter the balance between vasodilatation and vasoconstriction
      in favor of vasodilatation by increasing nitric oxide (NO) synthesis, by
      downregulating endothelin 1 (ET-1) synthesis and reducing vascular response to
      angiotensin-2 (AT-2). These agents have been shown to augment cerebral blood flow
      by upregulating endothelial nitric oxide synthase (eNOs) and to reduce cerebral
      infarct size in a murine model of cerebral ischemia. In addition, recent in vivo
      and in vitro investigations have evidenced that statins have a favorable effect
      on diabetic peripheral neuropathy independent of its lipid-lowering effect by
      demonstrating restoration or preservation of microcirculation of the sciatic
      nerve. We hypothesized that statins can be useful for the prevention and
      treatment of diabetic foot. Possible mechanisms include the reduction of
      neuropathy and ischemia or through growth factors, the effectiveness of which has
      been shown for fracture healing in animal models.

PMID- 17499448
TI  - Vitamin D deficiency may play a role in depression.
AB  - Vitamin D is known to be widely deficient in Western populations. The
      implications of this in terms of bone health are increasingly understood, yet its
      impact on other health areas, particularly mental health, is unclear. Recent data
      suggests that hypovitaminosis D may be common, especially in the elderly. Other
      studies have suggested that low levels of vitamin D are associated with poor
      mood. There are a number of trials that have suggested a role for Vitamin D in
      the supplementary treatment of depression. Dose may be a critical issue, as sun
      exposure and dietary intake may be low and high doses may be required.

PMID- 17499449
TI  - Coronary restenotic reduction of drug-eluting stenting may be due to its anti
      inflammatory effects.
AB  - The development of coronary stent has revolutionized the field of interventional
      cardiology by reducing the incidence of restenosis after balloon angioplasty.
      However, the stent has still associated with a serious complication, namely, in
      stent restenosis. Although, restenosis following coronary stenting has long been
      attributed to neointimal proliferation, thrombosis, and negative remodeling, the
      inflammation may be a trigger for those vascular reactions following coronary
      stenting. Both experimental and clinical studies have demonstrated a marked
      activation of local and systemic inflammatory response following stent
      implantation, suggesting that inflammation may play an important role in
      determining in-stent restenosis via neointimal proliferation. The key role of
      inflammation in vascular healing and in-stent retsenosis has also been
      increasingly well understood. Recently, drug-eluting stents (DESs) have been
      shown to decrease in-stent restenosis in a large number of clinical studies. In
      addition to their anti-proliferative activity, DESs have been considered to
      possess an anti-inflammatory property, especially for sirolimus-eluting stent
      compared with bare metal stent. Moreover, the benefit of the anti-inflammatory
      therapy during the peri-procedural period and long-term follow-up by means of
      drug administration is also dependent on the inflammatory status during
      percutaneous coronary intervention. Measurement of cytokine and acute phase
      proteins, such as C-reactive protein, therefore, may be important to identify
      high-risk subjects and develop specific treatment tailored to the individual
      patients with stent restenosis. Thus, therapeutic approach should be further
      directed toward increasing local resistance to proliferative inflammatory stimuli
      by means of anti-proliferative, locally delivered drugs and reducing the
      magnitude and persistence of systemic inflammation.

PMID- 17499450
TI  - The paradoxical advantages and disadvantages of natural selection: the case
      history of Charles Darwin.
AB  - The biology of natural selection is an enduring mystery, as is the nature of
      Charles Darwin's chronic illness. Of the theories advanced to explain the latter,
      Oedipal conflicts and Chagas' disease are preeminent. Hypomania, however,
      propelled Darwin to the pinnacle of scientific achievement and good health, the
      depression that followed condemning him to intellectual stagnation, lethargy,
      impaired memory and concentration, and incapacitating gastrointestinal disorders.
      Examples of natural selection in humans are much sought after when, ironically,
      one need look no further than Darwin himself.

PMID- 17499451
TI  - Moderately low alpha/beta ratio for rectal cancer may best explain the outcome of
      three fractionation schedules of preoperative radiotherapy.
AB  - PURPOSE: To estimate the alpha/beta ratio for rectal cancer according to the
      outcome of three fractionation schedules of preoperative radiotherapy. METHODS
      AND MATERIALS: Between 1996 and 2002, 168 patients with locally advanced rectal
      cancer were treated as follows: 53 patients received 25 Gy in 5 Gy per fraction,
      45 received 30 Gy in 3.0 Gy per fraction, and 70 were treated with accelerated
      hyperfractionation (42 Gy, 1.5 Gy per fraction, given twice daily). No patients
      received concurrent chemotherapy. The clinical characteristics of the groups were
      comparable. Surgery was performed shortly after radiotherapy. Crude data on
      locoregional tumor control were fitted directly using a linear-quadratic model,
      and the actuarial data were analyzed using Cox model. RESULTS: A linear-quadratic
      model provided an alpha estimate of 0.339 (SE 0.115) and beta estimate of 0.067
      (SE 0.027), which resulted in an alpha/beta ratio of 5.06 Gy (95% confidence
      interval -0.1 to 10.3). In all three schemes the overall radiation treatment time
      was short, which limits the rationales for incorporating time effect into the
      model. If, however, time was incorporated the alpha/beta ratio was 11.1 Gy and
      the dose increment required to compensate for repopulation was 0.15 Gy/day. The
      actuarial analysis provided similar alpha/beta estimates. CONCLUSION: Although
      because of the retrospective character of the study, nonrandomized selection of
      fractionation schedule, and uncontrolled quality of surgery the present results
      can be regarded as hypothesis generating only, the control rates obtained in the
      pelvis are consistent with a moderately low alpha/beta ratio for rectal cancer.

PMID- 17499452
TI  - Promising long-term health-related quality of life after high-dose-rate
      brachytherapy boost for localized prostate cancer.
AB  - PURPOSE: To explore the long-term general and disease-specific health-related
      quality of life (HRQOL) >5 years after combined radiotherapy for localized
      prostate cancer, including a high-dose-rate brachytherapy boost and hormonal
      deprivation therapy. METHODS AND MATERIALS: Of 196 eligible patients with
      localized prostate cancer (Stage T1-T3a) consecutively treated with curative
      radiotherapy at our institution between June 1998 and August 2000, 182 (93%)
      completed the European Organization for Research and Treatment of Cancer Quality
      of Life questionnaires QLQ-C30 and QLQ-PR25, including specific questions on
      fecal incontinence >5 years after treatment in September 2005. A comparison with
      age-matched normative data was done, as well as a longitudinal analysis using
      HRQOL data from a previous study. RESULTS: The analysis included 158 nonrecurrent
      patients. Comparisons made with normative data showed that physical and role
      functioning were significantly better statistically and social functioning was
      significantly worse. Diarrhea and sleep disturbances were more pronounced and
      pain less pronounced than in a normal male population. The longitudinal analysis
      of disease-specific HRQOL showed that urinary urgency and erectile problems
      persisted 5 years after treatment, and nocturia and hormonally dependent symptoms
      had declined significantly, with a statistically significant difference. Fecal
      incontinence was recognized by 25% of patients, of whom 80% considered it a minor
      problem. CONCLUSION: More than 5 years after combined radiotherapy, irritative
      urinary problems and erectile dysfunction remain concerns, although severe bowel
      disturbance and fecal incontinence seem to be minor problems. Longitudinally, a
      decline mainly in hormonally dependent symptoms was seen. Minor differences in
      general HRQOL compared with normative data were observed, possibly including
      "response shift" effects.

PMID- 17499453
TI  - Multifocal glioblastoma multiforme: prognostic factors and patterns of
      progression.
AB  - PURPOSE: To assess the progression patterns in patients with multifocal
      glioblastoma multiforme who had undergone whole brain radiotherapy (WBRT), the
      historical standard, versus three-dimensional conformal radiotherapy, and to
      identify predictive treatment and pretreatment factors. METHODS AND MATERIALS:
      The records of 50 patients with multifocal glioblastoma multiforme treated with
      RT were reviewed. Univariate analyses were performed using survival methods and
      the Cox proportional hazards regression method. Multivariate analyses were
      performed using the Cox proportional hazards regression method. RESULTS: The mean
      age was 61 years, and 71% had a Karnofsky performance status (KPS) score of > or
      =70. Of the 50 patients, 32% underwent WBRT and 68%, three-dimensional conformal
      RT. Progression was local in all evaluable patients, as determined by imaging in
      38 patients and early neurologic progression in 12. The median time to
      progression (TTP) was 3.1 months, and the median survival time (MST) was 8.1
      months. The significant independent predictors of TTP on multivariate analysis
      were a KPS score <70 (p = 0.001), the extent of surgery (p = 0.040), a radiation
      dose <60 Gy (p = 0.027), and the lack of chemotherapy (p = 0.001). The
      significant independent predictors of a reduced MST were a KPS score <70 (p =
      0.022) and the absence of salvage surgery (p = 0.011) and salvage chemotherapy (p
      = 0.003). CONCLUSION: Local progression was observed in all patients. On
      multivariate analysis, no significant difference was found in the TTP or MST
      between three-dimensional conformal radiotherapy and WBRT. The KPS was a
      consistent independent predictor of both TTP and MST. On the basis of the
      progression pattern, we do not recommend WBRT as a mandatory component of the
      treatment of multifocal glioblastoma multiforme.

PMID- 17499454
TI  - Phytochemical and antiprotozoal activity of Ocotea lancifolia.
AB  - Thirteen known isoquinoline alkaloids were isolated from Ocotea lancifolia,
      popularly known as << canela pilosa >> in Brasil and << laurel ne >> by the
      Guarani people which means smell laurel. Their activities against the
      promastigote forms of three Leishmania strains and the bloodstream form of
      Trypanosoma cruzi were evaluated, as well as their hepatocytotoxicity. Among
      them, the noraporphine alkaloid (-) caaverine has shown the most interesting
      antiprotozoal activity against Leishmania and T. cruzi parasites.

PMID- 17499455
TI  - [Can we still perform instrumental rotations using Thierry's spatula? Preliminary
      study among primiparous].
AB  - OBJECTIVES: To study immediate perineal and neonatal outcomes after instrumental
      rotational performed with Thierry's spatula among primiparous, and compare
      subsequent perineal tear with occiput posterior position delivery. MATERIALS AND
      METHODS: The study was performed from December 2005 to June 2006 at Paule-de
      Viguier hospital (Toulouse university hospital) including all persistent occiput
      posterior vaginal deliveries among primiparous (49 patients). Mode of delivery
      was: 1) seven patients with spontaneous occiput anterior vaginal delivery
      (14.3%); 2) seven patients with rotational extraction using spatula with occiput
      anterior delivery (30.6%); 3) twenty-seven patients with instrumental extraction
      and occiput posterior delivery (55.1%). Maternal and fetal parameters were
      studied prospectively. RESULTS: Spatula was performed for failure of progress in
      71.4% of cases (n=30) and for no reassuring fetal status in 28.6% of cases
      (n=12). In "rotational group", only one perineal tear was observed (Third degree)
      (6.6%) versus seven in "occiput posterior extraction group" (26%) with three
      severe perineal lacerations. Neonatal superficial lesions are frequent (26,6%
      after rotation versus 11.6% after occiput posterior extraction). None severe
      traumatic tears were observed. CONCLUSION: Instrumental rotation using Thierry's
      spatula seems to be less deleterious for maternal perineum than occiput posterior
      extraction, without increasing neonatal complications. Theses preliminary results
      have to be confirmed by more important prospective works.

PMID- 17499456
TI  - Brain activation during the Stroop task in adolescents with severe substance and
      conduct problems: A pilot study.
AB  - BACKGROUND: Although many neuroimaging studies have examined changes in brain
      function in adults with substance use disorders, far fewer have examined
      adolescents. This study investigated patterns of brain activation in adolescents
      with severe substance and conduct problems (SCP) compared to controls. METHODS:
      Functional magnetic resonance imaging (fMRI) at 1.5Tesla assessed brain
      activation in 12 adolescent males with SCP, ranging in age from 14 to 18, and 12
      controls similar in age, gender, and neighborhood while performing the
      attentionally demanding Stroop task. RESULTS: Even though the adolescents with
      SCP performed as well as the controls, they activated a more extensive set of
      brain structures for incongruent (e.g., "red" in blue ink) versus congruent (e.g.
      "red" in red ink) trials. These regions included parahippocampal regions
      bilaterally, posterior regions involved in language-related processing, right
      sided medial prefrontal areas, and subcortical regions including the thalamus and
      caudate. CONCLUSION: These preliminary results suggest that the neural mechanisms
      of attentional control in youth with SCP differ from youth without such problems.
      This difficulty may prevent SCP youth from ignoring salient but distracting
      information in the environment, such as drug-related information.

PMID- 17499457
TI  - The complete mitochondrial genome and phylogenetic analysis of the giant panda
      (Ailuropoda melanoleuca).
AB  - The complete mitochondrial genome sequence of the giant panda, Ailuropoda
      melanoleuca, was determined by the long and accurate polymerase chain reaction
      (LA-PCR) with conserved primers and primer walking sequence methods. The complete
      mitochondrial DNA is 16,805 nucleotides in length and contains two ribosomal RNA
      genes, 13 protein-coding genes, 22 transfer RNA genes and one control region. The
      total length of the 13 protein-coding genes is longer than the American black
      bear, brown bear and polar bear by 3 amino acids at the end of ND5 gene. The
      codon usage also followed the typical vertebrate pattern except for an unusual
      ATT start codon, which initiates the NADH dehydrogenase subunit 5 (ND5) gene. The
      molecular phylogenetic analysis was performed on the sequences of 12 concatenated
      heavy-strand encoded protein-coding genes, and suggested that the giant panda is
      most closely related to bears.

PMID- 17499458
TI  - Immunisation strategies against prion diseases: prime-boost immunisation with a
      PrP DNA vaccine containing foreign helper T-cell epitopes does not prevent mouse
      scrapie.
AB  - Vaccination against prion diseases constitutes a promising approach for the
      treatment and prevention of the disease. Passive immunisation with antibodies
      binding to the cellular prion protein (PrP(C)) can protect against prion disease.
      However, immunotherapeutic strategies with active immunisation are limited due to
      the immune tolerance against the self-antigen. In order to develop an anti-prion
      vaccine, we designed a novel DNA fusion vaccine composed of mouse PrP and immune
      stimulatory helper T-cell epitopes of the tetanus toxin that have previously been
      reported to break tolerance to other self-antigens. This approach provoked a
      strong PrP(C)-specific humoral and cellular immune response in PrP null mice, but
      only low antibody titres were found in vaccinated wild-type mice. Furthermore,
      prime-boost immunisation with the DNA vaccine and recombinant PrP protein
      increased antibody titres in PrP null mice, but failed to protect wild-type mice
      from mouse scrapie.

PMID- 17499459
TI  - An inactivated vaccine for the control of bluetongue virus serotype 16 infection
      in sheep in Italy.
AB  - Because no suitable products are at the moment available to safely control the
      spread of BTV-16 in Europe, an inactivated vaccine was produced from the
      reference field isolate of bluetongue virus serotype 16. One group of six sheep
      was vaccinated subcutaneously with the inactivated vaccine twice, on days 0 and
      28, whereas a second group of eight sheep was inoculated with saline solution and
      used as mock-vaccinated control animals. Seventy-eight days after the first
      vaccination, all sheep were inoculated subcutaneously with a suspension
      containing 10(6.3) TCID(50) of a virulent reference BTV-16 isolate. Apart from a
      transient inflammatory reaction at the injection site, no adverse effects were
      reported following vaccination. All vaccinated animals developed high titres (7.3
      9.3log(2)(ED50%/50 microl)) of virus-specific neutralising antibodies and were
      resistant to challenge with BTV-16. Conversely, following challenge, control
      animals developed hyperthermia and long lasting high-titre viraemia.

PMID- 17499460
TI  - Sertoli cell index and spermatic reserves in adult captive African lions
      (Panthera leo, Linnaeus, 1758).
AB  - The intrinsic yield of spermatogenesis and the supporting indexes of the Sertoli
      cells are the best indicators for the spermatic production capacity in a species.
      The aim of the present study was to quantify the intrinsic yield of the
      spermatogenetic process, as well as the Sertoli cell index and spermatic
      reserves. Testicular fragments of five adult African lions was fixed in 4%
      glutaric aldehyde, dehydrated at increasing alcohol concentrations, included into
      hydroxyethyl methacrylate, and were cut into 4 microm thickness. In the
      seminiferous epithelium of the African lions, 10.3 primary spermatocytes at pre
      leptotene phase are produced by the type-A spermatogonia. During meiotic
      divisions, only 2.7 spermatids were produced from the primary spermatocytes. The
      general spermatogenesis production in the African lions was approximately 22.1
      cells, and each Sertoli cell was able to sustain and maintain approximately 14.9
      cells of the germinative line, from which 7.9 are round spermatids. A total of
      103x10(6) spermatozoa are produced by each testis gram at each cycle of the
      seminiferous epithelium. The spermatic reserve of lion is below the amplitude
      observed in mammals.

PMID- 17499461
TI  - Silk fibroin mediated delivery of liposomal emodin to breast cancer cells.
AB  - The efficacy of a drug is dependent on its mode of delivery and its potency at
      the tumor site. In this study, the drug delivery and efficacy of silk fibroin
      coated liposomes (SF-ELP), encapsulating a receptor tyrosine kinase inhibitor,
      emodin, on Her2/neu over-expressing breast cancer cells, was investigated. This
      study demonstrates that SF-ELP was more efficacious in suppressing the growth of
      Her2/neu over-expressing breast cancer cells MDA-MB-453 and BT-474 as compared to
      uncoated emodin loaded liposomes (ELP). Reduced levels of phosphorylated Her2/neu
      correlated with growth inhibition observed in the MDA-MB-453 cells, treated with
      both ELP and SF-ELP. ELP treatment of MDA-MB-453 breast cancer cells resulted in
      inhibition of the PI3K pathway whereas SF-ELP treatment inhibited both the PI3K
      and MAPK pathways, which contributed to the enhanced growth inhibitory effects of
      Her2/neu over-expressing breast cancer cells. Coating of ELP with silk fibroin
      did not alter the target specificity of emodin, on the other hand the emodin
      efficacy was enhanced. Higher uptake of emodin delivered by SF-ELP lead to
      increased cell death as compared to emodin delivery via ELP. Silk fibroin coating
      around the liposome imparts an extra layer that emodin has to extravasate in
      order to release from the encapsulating liposome. This increases retention of the
      drug in the cell for a longer time and protects emodin from quick release and
      metabolism. Longer intracellular retention may lead to the longer availability of
      emodin for down-modulation of various Her2/neu pathways. This study demonstrates
      that silk fibroin coating enhanced emodin delivery in Her2/neu over-expressing
      breast cancer cells thereby increasing the overall efficacy of the drug.

PMID- 17499462
TI  - Purification of bioactive glycosylated recombinant glial cell line-derived
      neurotrophic factor.
AB  - Glial cell line-derived neurotrophic factor (GDNF) neuroprotective effect on
      dopaminergic neurons has been described in vitro and in vivo, turning up as a
      promising drug for the treatment of Parkinson's disease. Unglycosylated bacteria
      obtained GDNF has already been successfully delivered for a long period of time
      through an infusion pump directly to the putamen of Parkinsonian patients.
      Nevertheless, improved distribution and safety issues need to be solved and
      alternative strategies to long-term delivery seem necessary. The use of
      glycosylated GDNF could eliminate some safety concerns regarding the presence of
      antibodies against exogenous unglycosylated GDNF used for the treatment.
      Therefore, we have chosen a mammalian expression system as a source of
      glycosylated GDNF. In the present work, we describe the purification of
      recombinant rat GDNF from the culture media of baby hamster kidney (BHK) cells
      through several purification steps. Highly pure N-glycosylated recombinant GDNF
      has been obtained similar to the endogenous protein. Furthermore, the purified
      protein is biologically active when tested its ability to induce PC12 neurite
      outgrowth.

PMID- 17499463
TI  - Antiulcerogenic effect and acute toxicity of a hydroethanolic extract from the
      cashew (Anacardium occidentale L.) leaves.
AB  - The antiulcerogenic effect of a hydroethanolic extract of Anacardium occidentale
      L. leaves was investigated. The extract inhibited gastric lesions induced by
      HCl/ethanol in female rats. A dose-response effect study showed that the ED50 was
      150 mg/kgb.w. Extract doses higher than 100 mg/kgb.w. were more effective than 30
      mg/kg of lansoprazol in inhibiting gastric lesions. A methanolic fraction (257.12
      mg/kg) which reduced gastric lesion at 88.20% is likely to contain the active
      principle of the antiulcer effect. No signs of acute toxicity were observed when
      mice were treated with extract dose up to 2000 mg/kgb.w. A chemical analysis of
      the extract allowed the identification of phenolic compounds as the major
      components. Glycosylated quercetin, amentoflavone derivate and a tetramer of
      proanthocyanidin were identified by liquid chromatography coupled to mass
      spectrometry. The level of total phenolics in the extract was evaluated at 35.5%
      and flavonoid content was 2.58%.

PMID- 17499464
TI  - Surgical treatment versus concurrent chemoradiotherapy as an initial treatment
      modality in advanced olfactory neuroblastoma.
AB  - OBJECTIVE: Olfactory neuroblastomas are very aggressive tumors with a high
      locoregional recurrence rate and distant metastasis. Surgical treatment,
      including craniofacial resection, has been the main treatment modality, but
      treatment outcomes of concurrent chemoradiotherapy remain unclear. We present our
      experiences regarding the treatment outcome of patients with advanced olfactory
      neuroblastoma undergoing surgical treatment and concurrent chemoradiotherapy.
      METHODS: We retrospectively analyzed 16 patients treated for advanced olfactory
      neuroblastoma within the past 10 years. RESULTS: The disease-free 5-year survival
      rate of the patients (n = 10) who underwent surgical treatment was 68%. The
      survival rate for patients (n = 6) who received concurrent chemoradiotherapy was
      42%. The difference in the survival rate was not statistically significant, and
      no difference in the recurrence rate between the two groups. In the group having
      surgical treatment, post-operative radiotherapy and salvage therapy were
      important to increase the survival rate. In the group having concurrent
      chemoradiotherapy, no patient experienced primary tumor progression. CONCLUSION:
      Complete surgical resection, including craniofacial resection (CFR), and post
      operative radiotherapy seem to be essential in the treatment of advanced
      olfactory neuroblastoma. However, concurrent chemoradiotherapy may be another
      primary treatment modality.

PMID- 17499465
TI  - [Subcutaneous phaeomycotic cyst of the ankle].
AB  - Phaeohyphomycosis is a rare mycotic opportunist disease witch usually affects
      immunodepressed patients. Infection follows a traumatic inoculation of fungi into
      the skin with formation of a subcutaneous cyst. We report the case of a 20-year
      old woman presenting with a subcutaneous, painless, and recurrent cystic lesion
      on the right ankle for 9 years. A surgical excision was performed.
      Histopathologic examination showed a granuloma with central abscess surrounded by
      a thick fibrous tissue. After staining with PAS, septate hyphae and spores were
      found in the granuloma, consistent with a phaeomycotic cyst.

PMID- 17499466
TI  - High-resolution fMRI of macaque V1.
AB  - To understand the physiological mechanisms underlying the blood-oxygenation-level
      dependent (BOLD) signal, the acquisition of data must be optimized to achieve the
      maximum possible spatial resolution and specificity. The term "specificity"
      implies the selective enhancement of signals originating in the parenchyma, and
      thus best reflecting actual neural activity. Such spatial specificity is a
      prerequisite for imaging aimed at the elucidation of interactions between
      cortical micromodules, such as columns and laminae. In addition to the optimal
      selection of functional magnetic resonance imaging pulse sequences, accurate
      superposition of activation patterns onto corresponding anatomical scans,
      preferably acquired during the same experimental session, is necessary. At high
      resolution, exact functional-to-structural registration is of critical
      importance, because even small differences in geometry, that arise when different
      sequences are used for functional and anatomical scans, can lead to misallocation
      of activation and erroneous interpretation of data. In the present study, we used
      spin-echo (SE) echo planar imaging (EPI) for functional scans, since the SE-BOLD
      signal is sensitive to the capillary response, together with SE-EPI anatomical
      reference scans. The combination of these acquisition methods revealed a clear
      spatial colocalization of the largest fractional changes with the Gennari line,
      suggesting peak activity in Layer IV. Notably, this very same layer coincided
      with the largest relaxivity changes as observed in steady-state cerebral blood
      volume measurements, using the intravascular agent monocrystalline iron oxide
      nanoparticles (MION).

PMID- 17499468
TI  - Repeatability of echo-planar-based diffusion measurements of the human prostate
      at 3 T.
AB  - Echo-planar-based diffusion-weighted imaging (DWI) of the prostate is
      increasingly being suggested as a viable technique, complementing information
      derived from conventional magnetic resonance imaging methods for use in tissue
      discrimination. DWI has also been suggested as a potentially useful tool in the
      assessment of tumor response to treatment. In this study, the repeatability of
      apparent diffusion coefficient (ADC) values obtained from both DWI and diffusion
      tensor imaging (DTI) has been assessed as a precursor to determining the
      magnitude of treatment-induced changes required for reliable detection. The
      repeatability values of DWI and DTI were found to be similar, with ADC values
      repeatable to within 35% or less over a short time period of a few minutes and a
      longer time period of a month. Fractional anisotropy measurements were found to
      be less repeatable (between 26% and 71%), and any changes duly recorded in
      longitudinal studies must therefore be treated with a degree of caution.

PMID- 17499467
TI  - Assessing functional connectivity in the human brain by fMRI.
AB  - Functional magnetic resonance imaging (fMRI) is widely used to detect and
      delineate regions of the brain that change their level of activation in response
      to specific stimuli and tasks. Simple activation maps depict only the average
      level of engagement of different regions within distributed systems. FMRI
      potentially can reveal additional information about the degree to which
      components of large-scale neural systems are functionally coupled together to
      achieve specific tasks. In order to better understand how brain regions
      contribute to functionally connected circuits, it is necessary to record
      activation maps either as a function of different conditions, at different times
      or in different subjects. Data obtained under different conditions may then be
      analyzed by a variety of techniques to infer correlations and couplings between
      nodes in networks. Several multivariate statistical methods have been adapted and
      applied to analyze variations within such data. An approach of particular
      interest that is suited to studies of connectivity within single subjects makes
      use of acquisitions of runs of MRI images obtained while the brain is in a so
      called steady state, either at rest (i.e., without any specific stimulus or task)
      or in a condition of continuous activation. Interregional correlations between
      fluctuations of MRI signal potentially reveal functional connectivity. Recent
      studies have established that interregional correlations between different
      components of circuits in each of the visual, language, motor and working memory
      systems can be detected in the resting state. Correlations at baseline are
      changed during the performance of a continuous task. In this review, various
      methods available for assessing connectivity are described and evaluated.

PMID- 17499469
TI  - BOLD functional MRI in disease and pharmacological studies: room for improvement?
AB  - In the past decade the use of blood oxygen level-dependent (BOLD) fMRI to
      investigate the effect of diseases and pharmacological agents on brain activity
      has increased greatly. BOLD fMRI does not measure neural activity directly, but
      relies on a cascade of physiological events linking neural activity to the
      generation of MRI signal. However, most of the disease and pharmacological
      studies performed so far have interpreted changes in BOLD fMRI as "brain
      activation," ignoring the potential confounds that can arise through drug- or
      disease-induced modulation of events downstream of the neural activity. This
      issue is especially serious in diseases (like multiple sclerosis, brain tumours
      and stroke) and drugs (like anaesthetics or those with a vascular action) that
      are known to influence these physiological events. Here we provide evidence that,
      to extract meaningful information on brain activity in patient and
      pharmacological BOLD fMRI studies, it is important to identify, characterise and
      possibly correct these influences that potentially confound the results. We
      suggest a series of experimental measures to improve the interpretability of BOLD
      fMRI studies. We have ranked these according to their potential information and
      current practical feasibility. First-line, necessary improvements consist of (1)
      the inclusion of one or more control tasks, and (2) the recording of
      physiological parameters during scanning and subsequent correction of possible
      between-group differences. Second-line, highly recommended important aim to make
      the results of a patient or drug BOLD study more interpretable and include the
      assessment of (1) baseline brain perfusion, (2) vascular reactivity, (3) the
      inclusion of stimulus-related perfusion fMRI and (4) the recording of
      electrophysiological responses to the stimulus of interest. Finally, third-line,
      desirable improvements consist of the inclusion of (1) simultaneous EEG-fMRI, (2)
      cerebral blood volume and (3) rate of metabolic oxygen consumption measurements
      and, when relevant, (4) animal studies investigating signalling between neural
      cells and blood vessels.

PMID- 17499470
TI  - Validated HPLC-MS/MS method for determination of quetiapine in human plasma.
AB  - A validated, highly sensitive and selective high-pressure liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method was developed for the quantitative
      determination of quetiapine (QUE) in human Na2EDTA plasma with mass spectrometry
      (MS) detection. Clozapine (CLO) was employed as an internal standard. Samples
      were extracted using solid phase extraction (SPE). Oasis HLB cartridges and the
      concentration of quetiapine was determined by isocratic HPLC-MS/MS. The SRM mode
      was used for MS/MS detection. The method was validated over a concentration range
      of 1.0-382.2 ng/mL. Inter- and intra-day precision and accuracy of the proposed
      method were characterized by relative standard deviation (R.S.D.) and the
      percentage of deviation, respectively; both were lower than 8%. The developed
      method was employed in the pharmacokinetic study of quetiapine.

PMID- 17499471
TI  - A rapid method for the simultaneous determination of 11 saponins in Panax
      notoginseng using ultra performance liquid chromatography.
AB  - A rapid ultra performance liquid chromatography coupled with photo diode array
      detection method (UPLC-PDA) was developed for the simultaneous determination of
      11 saponins, namely notoginsenoside R1, ginsenoside Rg1, Re, Rf, Rb1, Rg2, Rc,
      Rb2, Rb3, Rd and Rg3 in Panax notoginseng. The analysis was performed on Acquity
      UPLC system with Acquity UPLC BEH C(18) column and gradient elution of water and
      acetonitrile in 12 min. The high correlation coefficient (r(2)>0.9968) values
      indicated good correlations between the investigated compounds' concentrations
      and their peak areas within the test ranges. The LOQ and LOD were lower to 0.2
      2.4 and 0.1-1.8 ng on column, respectively. The overall intra- and inter-day
      variations (R.S.D.) of 11 saponins were lower than 3.1%. The developed method was
      successfully used for the analysis of saponins in P. notoginseng with overall
      recovery of 93.0-101.6% for the analytes. The results show that UPLC is a
      powerful tool for analysis of components in Chinese medicines.

PMID- 17499472
TI  - Micelle-mediated extraction and cloud point preconcentration for the analysis of
      aesculin and aesculetin in Cortex fraxini by HPLC.
AB  - In this paper, a micelle-mediated extraction and cloud point preconcentration
      method was developed for the determination of less hydrophobic compounds aesculin
      and aesculetin in Cortex fraxini by HPLC. Non-ionic surfactant oligoethylene
      glycol monoalkyl ether (Genapol X-080) was employed as the extraction solvent.
      Various experimental conditions were investigated to optimize the extraction
      process. Under optimum conditions, i.e. 5% Genapol X-080 (w/v), pH 1.0,
      liquid/solid ratio of 400:1 (ml/g), ultrasonic-assisted extraction for 30 min,
      the extraction yield reached the highest value. For the preconcentration of
      aesculin and aesculetin by cloud point extraction (CPE), the solution was
      incubated in a thermostatic water bath at 55 degrees C for 30 min, and 20% NaCl
      (w/v) was added to the solution to facilitate the phase separation and increase
      the preconcentration factor during the CPE process. Compared with methanol, which
      was used in Chinese Pharmacopoeia (2005 edition) for the extraction of C.
      fraxini, the extraction efficiency of 5% Genapol X-080 reached higher value.

PMID- 17499473
TI  - A validated liquid chromatography method for the simultaneous determination of
      vitamins A and E in human plasma.
AB  - A fast (15 min) and simple HPLC method for determination of all-trans-retinol and
      alpha-, gamma- and delta-tocopherols in human plasma has been developed. The
      assay utilized 200 microl of plasma to which 20 microl of internal standard
      solution (retinol acetate) was added followed by 200 microl of water, 400 microl
      of ethanol and 800 microl of hexane. The hexane layer was collected, evaporated,
      the residue dissolved in 200 microl of methanol and analyzed on a Zorbax Eclipse
      XDB-C18 column using a step gradient with a polar organic mobile phase composed
      of acetonitrile and methanol and variable wavelength fluorescence detection. The
      quantification limits for all-trans-retinol and gamma-tocopherol were 20 ng/ml
      and for alpha- and delta-tocopherols 500 ng/ml and 10 ng/ml, respectively. The
      procedure was validated and applied to the analysis of plasma samples from the
      Baltimore Longitudinal Study of Aging.

PMID- 17499474
TI  - Reversal of elution order for profen acid enantiomers in normal phase LC on
      Chiralpak AD.
AB  - Enantiomeric separations of four 2-substituted propionic acid drugs and two
      related acids have been studied using normal phase liquid chromatography with
      amylose (tris 3,5-dimethylphenylcarbamate) coated on silica as support (Chiralpak
      AD). At standard conditions (i.e. flow-rate, 1.0 ml/min; column temperature, 30
      degrees C) the elution order can be reversed when the polar alcohol modifier in
      isohexane, 2-propanol, is replaced by methanol/ethanol 2:1. This is the case for
      ibuprofen with 2.5% (v/v) alcohol and for mandelic acid with 10% (v/v) alcohol
      using synthetic mixtures with unequal proportions of the respective enantiomer.
      Thermodynamic studies in the range 10-45 degrees C on retention and selectivity
      of ibuprofen and mandelic acid gave both linear and curved plots. These results
      stress the importance of investigating enantiomer elution order during the
      development of enantioselective methods when both old and new CSPs are evaluated.
      One should also keep in mind that reversal can take place for rather common
      analytes in well established enantioselective chromatographic systems.

PMID- 17499475
TI  - Lymphatic transfer studies with immunoglobulin scintigraphy after axillary
      surgery.
AB  - AIMS: The study objective was to investigate the effects of axillary lymph node
      clearance surgery on the function and morphology of the lymphatic system of the
      upper limb in women with breast cancer. METHODS: Nineteen women were studied
      before and 3 months after surgery. Fifteen were studied again 12 months after
      surgery. On each occasion, scintigraphy following intradermal hand webspace
      injection of Tc-99m-human polyclonal immunoglobulin was performed to include the
      affected upper limb and torso. RESULTS: There was considerable functional
      variability in response to surgery. Seven patients subsequently developed breast
      cancer-related lymphedema (BCRL). Neither lymph re-routing (defined as a change
      in lymph vessel morphology or definition) nor linear velocity of protein transit
      up the arm was associated with the development of BCRL. Blood pool activity,
      judged from visual inspection of the cardiac blood pool on the whole body images,
      was earlier and more marked 3 and 12 months after surgery than before. The count
      rate (per 100 pixels/MBq injected activity), measured in a cardiac region of
      interest, was significantly higher after surgery than before, was higher in
      patients who developed BCRL and, in the patient population as a whole, correlated
      positively with arm swelling. CONCLUSION: The consequences of axillary lymph node
      clearance were variable, unexpected and largely persistent. An increased rate of
      access of intradermally injected protein into the blood pool is significantly
      associated with BCRL.

PMID- 17499476
TI  - Characterization of the FAM110 gene family.
AB  - We have previously characterized the centrosome/spindle pole-associated protein
      (CSPP) involved in cell cycle progression. The open reading frame C20orf55 was
      identified in a yeast two-hybrid screen in a search for CSPP-interacting
      proteins. A homology search revealed that C20orf55 belongs to a gene family
      consisting of three members that have not yet been described. The HUGO
      Nomenclature Committee has assigned these genes the names FAM110A-FAM110C.
      Studies of transfectants showed that the FAM110 proteins localized to centrosomes
      and accumulated at the microtubule organization center in interphase and at
      spindle poles in mitosis. In addition, overexpression of FAM110C induced
      microtubule aberrancies. Our data also indicated a cell cycle-regulated
      expression of FAM110A. Moreover, ectopic expression of FAM110B and FAM110C
      proteins impaired cell cycle progression in G1 phase. To summarize, we have
      characterized a novel family of genes encoding proteins with distinct conserved
      motifs, of which all members localize to centrosomes and spindle poles.

PMID- 17499477
TI  - Patterns of gene duplication and intron loss in the ENCODE regions suggest a
      confounding factor.
AB  - The exon-intron structure of eukaryotic genes allows for phenomena such as
      alternative splicing, nonsense-mediated decay, and regulation through
      untranslated regions. However, the evolution of the exon structure of genes is
      not well elucidated because of limited and phylogenetically sparse data sets. In
      this study, we use the phylogenetically diverse sequencing of the ENCODE regions
      to study gene structure evolution in mammalian genomes. This first
      phylogenetically diverse study of gene structure changes offers insights into the
      mode and tempo of mammalian gene structure evolution. The genes undergoing
      structure changes appear to be moderately to highly expressed in germline cells
      and show levels of selection similar to those of other ENCODE genes. Patterns of
      gene duplication of the affected genes are more complex than expected. The number
      of sampled genomes is sufficiently dense to infer that certain gene duplications
      happened after intron loss. Thus, although gene duplication is highly correlated
      with intron loss, we conclude that structural changes in genes are not
      necessarily due to a loss of constraint following gene duplication as previously
      suggested.

PMID- 17499478
TI  - Effects of environmental tobacco smoke in vitro on rhesus monkey sperm function.
AB  - The objective of this study was to use a non-human primate model to examine the
      effect of ETS on sperm function. Sperm samples were collected from adult rhesus
      monkeys (Macaca mulatta) and treated with different levels of ETS exposed medium.
      ETS treatment decreased the percentage of motile sperm and motion parameters.
      Sperm treated with ETS exposed medium showed a limited response to the activators
      and exhibited decreased binding to the zonae pellucida after activation. The
      mitochondrial integrity of the ETS-treated sperm was disrupted; however, there
      was no decrease in viability compared to control groups. Sperm acrosomal status
      was similar in the control and treatment groups. The results imply that the
      exposure of primate sperm to ETS could impair sperm transport in vivo.

PMID- 17499479
TI  - Bipaddled radial forearm flap for the reconstruction of bilateral buccal defects
      in oral submucous fibrosis.
AB  - Oral submucous fibrosis can result in progressive closure of the mouth. A total
      of 10 patients with advanced oral submucous fibrosis were surgically treated. The
      procedure consisted of (1) release of all the intraoral fibrotic tissue, (2)
      masticatory muscle myotomy and coronoidotomy, and (3) reconstruction with a
      bipaddled radial forearm flap. Preoperative mouth opening was 0-5mm (mean 2.3mm).
      The intraoperative mouth opening was 12-20mm (mean 16 mm) after submucous
      release, and 32-42 mm (mean 35.5mm) after further release via myotomy and
      coronoidotomy. The proximal flap included one perforator in four patients and two
      perforators in the remaining six patients. The flaps were 8-9 cm in length and 2
      2.5 cm in width. Nine flaps survived uneventfully. Arterial thrombosis was noted
      in one flap, which was successfully salvaged. Temporomandibular joint subluxation
      developed in one patient. Two patients needed flap revision due to bulkiness. The
      postoperative mouth opening was 18-38 mm (mean 28.2mm) after a mean of 21 months'
      follow-up, and the mean increase was 25.9 mm. A bipaddled radial forearm flap,
      using a single donor site, can cover two separate buccal defects after release of
      oral submucosal fibrosis and obviate the need for a second free flap.

PMID- 17499480
TI  - The relationship between symptomatic remission and neuropsychological improvement
      in schizophrenia patients switched to treatment with ziprasidone.
AB  - BACKGROUND: A definition of clinical remission in schizophrenia has recently been
      proposed. However, it is also known that neuropsychological (NP) impairments may
      be better predictors of functional outcomes than clinical symptoms. Understanding
      the relationship between clinical remission and cognitive improvement may be
      required in order to predict functional improvements, so we examined the
      development and convergence of clinical remission and neuropsychological
      improvements in a sample of patients with schizophrenia whose medication was
      switched to ziprasidone. METHODS: One hundred eighty-four patients were switched
      from their previous treatment with risperidone, olanzapine, or conventional
      antipsychotics to open-label ziprasidone treatment. One hundred and thirty seven
      patients were not in remission at baseline and 40 met the clinical criteria for
      remission at study entry. We rated their symptoms with the PANSS at baseline and
      after 6 months of treatment. We performed an NP assessment and generated a
      composite score which was examined for improvements. RESULTS: Of the 184 cases,
      48 (26.1% of the total sample) met the remission criteria at baseline. Of these
      cases, 41 (85%) sustained their remission at the 6-month follow-up. Of the
      remaining 136 cases, 33% developed remission by the 6-month follow-up. Thus, a
      total of 55% of the total sample were in remission at the 6-month endpoint. A
      comparable number of the patients, 34%, improved by 0.5 SD or more in their
      cognitive performance. Baseline NP performance was not associated with remission
      at baseline and did not predict achieving remission over time. Further, clinical
      remission was not correlated with concurrent NP improvements. However, 33
      patients achieved clinical remission and improved by 0.5 SD in their NP
      performance. IMPLICATIONS: After a switch from previous treatment to open-label
      ziprasidone more than half of patients with schizophrenia experienced sustained
      clinical remission over 6 months and 32% of the patients achieving remission
      experienced a concurrent NP improvement. Later research will be required to
      determine which aspects of improvement (clinical remission and/or cognitive
      improvements) are required for functional improvements.

PMID- 17499481
TI  - Comparison of age-related changes in facial wrinkles and sagging in the skin of
      Japanese, Chinese and Thai women.
AB  - BACKGROUND: Differences in skin aging features between Asians and Caucasians are
      commonly known, whereas little is known about such differences in various Asian
      populations. OBJECTIVE: A survey was carried out in Tokyo, Shanghai and Bangkok
      to identify specific features of skin aging in each population and to evaluate
      whether our conventional photo scale is an appropriate tool for this type of
      comparative study. METHODS: Eighty-seven women residing in Tokyo, 100 women
      residing in Shanghai, and 90 women residing in Bangkok were examined by a
      specialist. Facial wrinkles (forehead, glabella, upper eyelid, crow's feet, lower
      eyelid, cheek, nasolabial groove and mouth corner) and cheek sagging were
      evaluated using photo scales previously obtained from Japanese subjects.
      Comparisons were made according to 10-year age groups. RESULTS: Women in Bangkok
      showed the most severe level of wrinkles, followed by those in Shanghai in the
      three groups. Significant differences were observed between Thai and Japanese
      women in the intensity of wrinkles at many facial sites. Chinese women had
      significantly more severe wrinkles in the area around the eyes compared to
      Japanese women, while Thai women had significantly more severe wrinkles in the
      lower halves of their faces compared to Chinese women. In cheek sagging scores,
      significant differences were observed between Japanese and Thai women in their
      30s and 50s, but not between Japanese and Chinese women or between Chinese and
      Thai women in all age groups. CONCLUSION: These results indicate variations in
      skin aging features among women from three Asian cities thereby suggesting the
      diversity of Asian skin. Our scaling method proved to be appropriate for facial
      wrinkles, but required modification to compare cheek sagging among Asian
      populations.

PMID- 17499482
TI  - The missing care bundle: antibiotic prescribing in hospitals.
AB  - The care bundle involves grouping together key elements of care for procedures
      and the management of specific diagnoses in order to provide a systematic method
      to improve and monitor the delivery of clinical care processes. In short, care
      bundles aim to ensure that all patients consistently receive the best care or
      treatment, all of the time. This approach has been successfully applied to the
      management of various conditions, particularly in the critical care setting. The
      Institute for Healthcare Improvement's '100K lives campaign' consisted of six
      care bundles, three of which have addressed preventing hospital-acquired
      infection. The UK Department of Health's delivery programme to reduce healthcare
      associated infections (HCAIs), including methicillin-resistant Staphylococcus
      aureus (MRSA), includes six 'high-impact interventions', which are care bundles
      to reduce HCAIs. However, we suggest that one key intervention is missing, and
      consider this intervention will be increasingly important if hospitals are to
      address the rising incidence of Clostridium difficile, to tackle antibiotic
      resistance and to improve patient care. The missing intervention addresses the
      process of antibiotic prescribing. We propose that the time is right to consider
      the application of the care bundle approach to improve the prescribing of
      antibiotics, both for treatment and prophylaxis.

PMID- 17499483
TI  - Elevated small GTPase activation influences the cell proliferation signaling
      control in Niemann-Pick type C fibroblasts.
AB  - Niemann-Pick type C (NPC) disease is characterized at the cellular level by the
      intracellular accumulation of free cholesterol. We have previously identified a
      similar phenotype in cystic fibrosis (CF) cell models that results in the
      activation of the small GTPase RhoA. The hypothesis of this study was that NPC
      cells would also exhibit an increase in small GTPase activation. An examination
      of the active, GTP-bound form of GTPases revealed a basal increase in the content
      of the active-form Ras and RhoA small GTPases in NPC fibroblasts compared to wt
      controls. To assess whether this increase in GTP-bound Ras and RhoA manifests a
      functional outcome, the expression of the proliferation control proteins p21/waf1
      and cyclin D were examined. Consistent with increased GTPase signaling, p21/waf1
      expression is reduced and cyclin D expression is elevated in NPC fibroblasts.
      Interestingly, cell growth rate is not altered in NPC fibroblasts compared to wt
      cells. However, NPC sensitivity to statin treatment is reversed by addition of
      the isoprenoid geranylgeranyl pyrophosphate (GGPP), a modifier of RhoA. It is
      concluded that Ras and RhoA basal activation is elevated in NPC fibroblasts and
      has an impact on cell survival pathways.

PMID- 17499484
TI  - Increased plasma macrophage inflammatory protein (MIP)-1alpha and MIP-1beta
      levels in type 1 Gaucher disease.
AB  - Pancytopenia, hepatosplenomegaly and skeletal complications are hallmarks of
      Gaucher disease. Monitoring of the outcome of therapy on skeletal status of
      Gaucher patients is problematic since currently available imaging techniques are
      expensive and not widely accessible. The availability of a blood test that
      relates to skeletal manifestations would be very valuable. We here report that
      macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, both implicated in
      skeletal complications in multiple myeloma (MM), are significantly elevated in
      plasma of Gaucher patients. Plasma MIP-1alpha of patients (median 78 pg/ml, range
      21-550 pg/ml, n=48) is elevated (normal median 9 pg/ml, range 0-208 pg/ml, n=39).
      Plasma MIP-1beta of patients (median 201 pg/ml, range 59-647 pg/ml, n=49) is even
      more pronouncedly increased (normal median 17 pg/ml, range 1-41 pg/ml, n=39; one
      outlier: 122 pg/ml). The increase in plasma MIP-1beta levels of Gaucher patients
      is associated with skeletal disease. The plasma levels of both chemokines
      decrease upon effective therapy. Lack of reduction of plasma MIP-1beta below 85
      pg/ml during 5 years of therapy was observed in patients with ongoing skeletal
      disease. In conclusion, MIP-1alpha and MIP-1beta are elevated in plasma of
      Gaucher patients and remaining high levels of MIP-1beta during therapy seem
      associated with ongoing skeletal disease.

PMID- 17499485
TI  - Visual presentation of phobic stimuli: amygdala activation via an
      extrageniculostriate pathway?
AB  - In the present study, event-related functional magnetic resonance imaging (fMRI)
      was used to examine the neural correlates of phobic fear by exposing spider
      phobic subjects to a visual presentation of spiders. In contrast to control
      subjects, spider phobics showed significantly increased activation in the
      amygdala and the pulvinar nucleus of the thalamus on the basis of region of
      interest (ROI) analysis. Furthermore, voxelwise analysis revealed increased
      activation related to phobia-specific pictures bilaterally in the anterior
      cingulate cortex, the left insular cortex and bilaterally in the supplementary
      motor area. These findings confirm the involvement of the amygdala in the
      processing of phobia-relevant stimuli as found earlier in a recent study.
      Moreover, the thalamus findings support the involvement of an
      extrageniculostriate pathway in the process of phobic fear.

PMID- 17499486
TI  - Vesicle size and stability of biomimetic liposomes from 3'-sulfo-Lewis a (SuLea)
      containing glycolipids.
AB  - We report on the use of a natural Lewis type saccharide ligand, 3'-sulfo-Lewis a
      (SuLe(a)) for glycocalyx-mimetic surface modification of liposomes. Two SuLe(a)
      containing glycolipids, monovalent SuLe(a)-lipid and trivalent SuLe(a) (TSuLe(a))
      lipid, were synthesized, and used with 1,2-distearoyl-sn-glycero-3-phosphocholine
      (DSPC) and cholesterol to prepare unilaminar vesicles (ULVs) by a freeze-thaw and
      extrusion method. The effects of the glycolipid concentrations and the pore sizes
      of extrusion membranes on vesicle size and stability were investigated by photon
      correlation spectroscopy (PCS). Glycoliposomes, with 5% SuLe(a)- or TSuLe(a)
      lipids obtained by 50 nm extrusion, had 25-30% more vesicles less than 100 nm in
      diameter compared with the 100 nm extrusion. TSuLe(a)-liposomes always produced
      larger vesicle size than SuLe(a)-liposomes, which we attribute to the larger
      TSuLe(a) headgroup. Both SuLe(a)- and TSuLe(a)-liposomes increased their vesicle
      size with increasing glycolipid concentration from 5% to 15%, and demonstrated
      good stability at room temperature for over 1 month. Further increasing the
      glycolipid concentration to 20% resulted in large vesicle aggregation after 5
      days for TSuLe(a)-liposomes, while the SuLe(a)-liposomes remained stable for 10
      days. SuLe(a)- and TSuLe(a)-liposomes with 15% glycolipids demonstrated better
      stability due to the electrostatic effect from the negatively charged SuLe(a) and
      TSuLe(a) headgroups. The results indicate that the biomimetic liposomes with
      SuLe(a)- and TSuLe(a)-lipids with 5 to 15% incorporation are sufficiently stable
      for the potential applications in targeted drug delivery.

PMID- 17499487
TI  - Interactions of ADP-stimulated human platelets with PEGylated polystyrene
      substrates prepared by surface amidation.
AB  - A study primarily focused on the interactions between ADP-stimulated human
      platelets and PEGylated polystyrene substrates is described in this paper. The
      platelet-surface interactions were investigated using colorimetric acid
      phosphatase assay. Two types of amine-containing polymeric hydrogel materials
      based on poly(ethylene glycol) (PEG), H(2)N-PEG-OCH(3) and H(2)N-PEG-NH(2), were
      used to PEGylate polystyrene surfaces derivatized with maleic anhydride by
      amidation at alkaline pH. In addition, comparative studies using surfaces non
      covalently adsorbed by bovine serum albumin (BSA) or fibrinogen (Fg) were also
      conducted. The assay results showed that no significant platelet adhesion was
      observed when PEGylated surfaces or BSA-coated surfaces were exposed to
      unstimulated gel-filtered platelets (GFP). However, upon ADP-stimulation,
      platelet adhesion to the surfaces under investigation in this study all increased
      to varying degrees. Most importantly, the results showed that polystyrene
      surfaces PEGylated using H(2)N-PEG-NH(2) were most effective in resisting
      platelet adhesion when assays were performed using ADP-stimulated GFP. By
      PEGylating the surfaces of polystyrene microtiter wells via the amidation
      reaction described in this paper, it is demonstrated that (i) higher degree of
      surface PEGylation is favored at more alkaline pH and (ii) polystyrene substrates
      capable of more effectively resisting the adhesion of ADP-stimulated GFP can be
      obtained by the PEGylation reaction carried out at pH 9.1 using H(2)N-PEG-NH(2).

PMID- 17499488
TI  - Mechanical stretch promotes proliferation of rat bone marrow mesenchymal stem
      cells.
AB  - Tissues and cells in the body are continuously exposed to a complex mechanical
      environment. Mechanical stimulations are critical to morphological, developmental
      and functional states of living cells, and the fashion of the mechanical
      stimulation applied to the cells is supposed to be extremely important for the
      induced cell response and function. In this study, we investigated whether
      mechanical stretch regulates and promotes proliferation of rat bone marrow
      mesenchymal stem cells (rMSCs) in vitro. rMSCs from rat bone marrow were
      isolated, purified and subjected to a cyclic equiaxial stretch treatment, and
      then MTT assay was adopted and expression of c-fos gene was measured by RT-PCR to
      access cell proliferation. The results demonstrated that OD values of rMSCs
      increased in a time-dependent and magnitude-dependent manner after exposure to 1
      Hz stretch within 15-60 min and 2-8% strain. Expression of c-fos gene in rMSCs
      subjected to stretch treatment (1 Hz, 8% strain and 60 min) is significantly
      higher than that of unstimulated control cells. These results suggest that
      mechanical stretch plays an important role in regulating the cell growth and
      proliferation, and an appropriate mechanical stretch treatment could promote
      proliferating capacity of rMSCs.

PMID- 17499489
TI  - A novel, compact disk-like centrifugal microfluidics system for cell lysis and
      sample homogenization.
AB  - In this paper, we present the design and characterization of a novel platform for
      mechanical cell lysis of even the most difficult to lyse cell types on a micro or
      nanoscale (maximum 70 microL total volume). The system incorporates a machined
      plastic circular disk assembly, magnetic field actuated microfluidics,
      centrifugal cells and tissue homogenizer and centrifugation system. The mechanism
      of tissue disruption of this novel cell homogenization apparatus derives from the
      relative motion of ferromagnetic metal disks and grinding matrices in a liquid
      medium within individual chambers of the disk in the presence of an oscillating
      magnetic field. The oscillation of the ferromagnetic disks or blades produces
      mechanical impaction and shear forces capable of disrupting cells within the
      chamber both by direct action of the blade and by the motion of the surrounding
      lysis matrix, and by motion induced vortexing of buffer fluid. Glass beads or
      other grinding media are integrated into each lysis chamber within the disk to
      enhance the transfer of energy from the oscillating metal blade to the cells. The
      system also achieves the centrifugal elimination of solids from each liquid
      sample and allows the elution of clarified supernatants via siphoning into a
      collection chamber fabricated into the plastic disk assembly. This article
      describes system design, implementation and validation of proof of concept on two
      samples--Escherichia coli and Saccharomyces cerevisiae representing model systems
      for cells that are easy and difficult to lyse, respectively.

PMID- 17499490
TI  - Detection of occult spinal cord compression with magnetic resonance imaging of
      the spine.
AB  - AIMS: Spinal cord compression (SCC) is the most significant complication due to
      skeletal metastasis from prostate cancer. The early detection of SCC is essential
      as the neurological status before treatment is the major determinant influencing
      outcome. The aim of this investigation was to determine the role of magnetic
      resonance imaging of the spine in detecting SCC or occult SCC in patients with
      metastatic prostate cancer with no functional neurological deficit (FND).
      MATERIALS AND METHODS: A retrospective analysis of the clinical data of 150
      consecutive patients with metastatic prostate cancer and no FND, who had MRI of
      the spine from January 2001 to May 2005, was carried out. 'Overt SCC' on MRI was
      defined as the involvement or compression of either the spinal cord or the cauda
      equina by an epidural or intramedullary mass lesion and 'occult SCC' as
      metastatic disease causing impingement, indentation or loss of definition of the
      thecal sac, which were considered together for statistical purposes as
      radiological spinal cord compromise (rSCC). RESULTS: Twenty-four (16%) patients
      had overt SCC, whereas 17 (11.3%) patients had occult SCC. Seven patients had
      rSCC at multiple non-contiguous sites. The significant clinical determinants of
      rSCC on univariate analysis were extensive bone metastasis (P=0.005) and back
      pain (P=0.002). On multivariate analysis, both back pain (P=0.012) and extensive
      bone metastasis (P=0.047) significantly predicted for rSCC. CONCLUSION: A
      significant proportion (27.3%) of patients with metastatic prostate cancer may
      harbour overt or occult SCC in the absence of FND. MRI of the spine for the early
      diagnosis of SCC may be considered useful in patients with extensive skeletal
      metastasis and back pain.

PMID- 17499491
TI  - MMPs-specific PEGylated peptide-DOX conjugate micelles that can contain free
      doxorubicin.
AB  - The goal of this study was to develop anti-cancer drug conjugates with increased
      anti-tumor effect and reduced toxicity. In this regard, we utilized the
      physiological characteristics of tumors such as angiogenesis, the expression of
      matrix metalloproteinases (MMPs) and the enhanced permeability and retention
      (EPR) effect, and designed MMPs-specific PEGylated peptide-DOX conjugate micelles
      containing doxorubicin. These conjugates were prepared by using two peptides,
      GPLGV and GPLGVRG (P5D and P7D, respectively), and doxorubicin was loaded into
      micelles formed by each conjugate. P5D and P7D were specifically cleaved by
      active MMP-2 and all conjugates showed significantly better cell viability than
      doxorubicin at equivalent concentrations. In vivo, animals treated with PEGylated
      peptide-DOX conjugate micelles showed approximately 50% of the tumor growth of
      the control, and doxorubicin-loaded conjugates micelles inhibited tumor growth up
      to about 72% compared with the control, which matched the effect of doxorubicin.
      Doxorubicin-loaded PEGylated peptide-DOX conjugate micelles exhibited longer half
      lives and maintained higher concentrations of doxorubicin in plasma than
      PEGylated peptide-DOX conjugate micelles alone. Doxorubicin-loaded PEGylated
      peptide-DOX conjugate micelles might offer a cancer therapy with an activity that
      is similar to that of the parent drug but with reduced toxicity.

PMID- 17499492
TI  - Microscopic image analysis techniques for the morphological characterization of
      pharmaceutical particles: influence of the software, and the factor algorithms
      used in the shape factor estimation.
AB  - The present report highlights the difficulties of particle shape
      characterizations of multiparticulate systems obtained using different image
      analysis techniques. The report describes and discusses a number of shape factors
      that are widely used in pharmaceutical research. Using photographs of 16 pellets
      of different shapes, obtained by extrusion-spheronization, we investigated how
      shape factor estimates vary depending on method of calculation, and among
      different software packages. The results obtained indicate that the algorithms
      used (both for estimation of basic dimensions such as perimeter and maximum
      diameter, and for estimation of shape factors on the basis of these basic
      dimensions) have marked influences on the shape factor values obtained. These
      findings suggest that care is required when comparing results obtained using
      different image analysis programs.

PMID- 17499493
TI  - Embryonic development of Python sebae - I: Staging criteria and macroscopic
      skeletal morphogenesis of the head and limbs.
AB  - This study explores the post-ovipositional craniofacial development of the
      African Rock Python (Python sebae). We first describe a staging system based on
      external characteristics and next use whole-mount skeletal staining supplemented
      with Computed tomography (CT) scanning to examine skeletal development. Our
      results show that python embryos are in early stages of organogenesis at the time
      of laying, with separate facial prominences and pharyngeal clefts still visible.
      Limb buds are also visible. By 11 days (stage 3), the chondrocranium is nearly
      fully formed; however, few intramembranous bones can be detected. One week later
      (stage 4), many of the intramembranous upper and lower jaw bones are visible but
      the calvaria are not present. Skeletal elements in the limbs also begin to form.
      Between stages 4 (day 18) and 7 (day 44), the complete set of intramembranous
      bones in the jaws and calvaria develops. Hindlimb development does not progress
      beyond stage 6 (33 days) and remains rudimentary throughout adult life. In
      contrast to other reptiles, there are two rows of teeth in the upper jaw. The
      outer tooth row is attached to the maxillary and premaxillary bones, whereas the
      inner row is attached to the pterygoid and palatine bones. Erupted teeth can be
      seen in whole-mount stage 10 specimens and are present in an unerupted,
      mineralized state at stage 7. Micro-CT analysis reveals that all the young
      membranous bones can be recognized even out of the context of the skull. These
      data demonstrate intrinsic patterning of the intramembranous bones, even though
      they form without a cartilaginous template. In addition, intramembranous bone
      morphology is established prior to muscle function, which can influence bone
      shape through differential force application. After careful staging, we conclude
      that python skeletal development occurs slowly enough to observe in good detail
      the early stages of craniofacial skeletogenesis. Thus, reptilian animal models
      will offer unique opportunities for understanding the early influences that
      contribute to perinatal bone shape.

PMID- 17499494
TI  - Immobilization of acetylcholinesterase on gold nanoparticles embedded in sol-gel
      film for amperometric detection of organophosphorous insecticide.
AB  - A simple method to immobilize acetylcholinesterase (AChE) on silica sol-gel
      (SiSG) film assembling gold nanoparticles (AuNPs) was proposed, thus a sensitive,
      fast and stable amperometric sensor for quantitative determination of
      organophosphorous insecticide was developed. The large quantities of hydroxyl
      groups in the sol-gel composite provided a biocompatible microenvironment around
      enzyme molecule and stabilized its biological activity to a large extent. The
      immobilized AChE could catalyze the hydrolysis of acetylthiocholine chloride
      (ATCl) with a Kmapp value of 450 microM to form thiocholine, which was then
      oxidized to produce detectable single with a linear range of 10-1000 microM.
      AuNPs catalyzed the electro-oxidation of thiocholine, thus increasing detection
      sensitivity. Based on the inhibition of organophosphorous insecticide on the
      enzymatic activity of AChE, using monocrotophos as a model compound, the
      conditions for detection of the insecticide were optimized. The inhibition of
      monocrotophos was proportional to its concentration ranging from 0.001 to 1
      microg/ml and 2 to 15 microg/ml, with the correlation coefficients of 0.9930 and
      0.9985, respectively. The detection limit was 0.6 ng/ml at a 10% inhibition. The
      developed biosensor exhibited good reproducibility and acceptable stability, thus
      providing a new promising tool for analysis of enzyme inhibitors.

PMID- 17499495
TI  - Protein kinase signaling in synaptic plasticity and memory.
AB  - The relay of extracellular signals into changes in cellular physiology involves a
      Byzantine array of intracellular signaling pathways, of which cytoplasmic protein
      kinases are a crucial component. In the nervous system, a great deal of effort
      has focused on understanding the conversion of patterns of synaptic activity into
      long-lasting changes in synaptic efficacy that are thought to underlie memory.
      The goal is both to understand synaptic plasticity mechanisms, such as long-term
      potentiation, at a molecular level and to understand the relationship of these
      synaptic mechanisms to behavioral memory. Although both involve the activation of
      multiple signaling pathways, recent studies are beginning to define discrete
      roles and mechanisms for individual kinases in the different temporal phases of
      both synaptic and behavioral plasticity.

PMID- 17499496
TI  - High-resolution quantitative visualization of glutamate and GABA receptors at
      central synapses.
AB  - Glutamate and GABA are the main transmitters in the central nervous system and
      their effects are mediated by ionotropic and metabotropic receptors. Immunogold
      electron microscopy has revealed the quantitative localization of these receptors
      at 20-30nm resolution. SDS-digested freeze-fracture replica labeling (SDS-FRL), a
      newly developed immunogold method, provides an accurate estimate of molecule
      numbers. Here, we summarize the recent advances in quantitative receptor
      localization, including use of SDS-FRL analyses to determine numbers of AMPA-type
      glutamate receptors in the cerebellum. The two-dimensional view and high
      sensitivity of SDS-FRL have revealed small, irregularly shaped AMPA receptor
      clusters within cerebellar synapses.

PMID- 17499497
TI  - Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease.
AB  - Mutations in PARKIN, PTEN-induced kinase 1 (PINK1) and DJ-1 are found in
      autosomal recessive forms and some sporadic cases of Parkinson's disease. Recent
      work on these genes underscores the central importance of mitochondrial
      dysfunction and oxidative stress in Parkinson's disease. In particular, pink1 and
      parkin loss-of-function mutants in Drosophila show similar phenotypes, and pink1
      acts upstream of parkin in a common genetic pathway to regulate mitochondrial
      function. DJ-1 has a role in oxidative stress protection, but a direct role of DJ
      1 in mitochondrial function has not been fully established. Importantly, defects
      in mitochondrial function have also been identified in patients who carry both
      PINK1 and PARKIN mutations, and in those who have sporadic Parkinson's disease.
      Future studies of the biochemical interactions between Pink1 and Parkin, and
      identification of other components in this pathway, are likely to provide insight
      into Parkinson's disease pathogenesis, and might identify new therapeutic
      targets.

PMID- 17499498
TI  - Radiological staging of colorectal liver metastases.
AB  - Rapid advances in imaging technology have improved the detection,
      characterization and staging of colorectal liver metastases. Multi-modality
      imaging approach is usually the more useful in staging colorectal liver
      metastases. Multi-detector computed tomography (MDCT) remains the main imaging
      modality for preoperative planning, lesion detection and tumour surveillance.
      Magnetic resonance imaging (MRI) and contrast enhanced ultrasonography (US) are
      invaluable in problem solving for characterization indeterminate lesions, while
      contrast enhanced intra-operative ultrasound (CE-IOUS) may be the new gold
      standard staging tool prior to liver resection. Ultimately, the imaging strategy
      has to be tailored to the clinical situation to obtain the most relevant
      information for optimal use of available imaging resources.

PMID- 17499499
TI  - Radiofrequency ablation of colorectal liver metastases.
AB  - RFA of liver metastases is promising despite variable results. The differences in
      reported success rates may be explained by the difference in tumour
      types/vascularity/aggressiveness, patient selection, operator's expertise and the
      equipment used. Current limits relate to the small volume of consistent ablation
      that can be achieved with current equipment. Further technical refinements
      yielding more reliable ablation with larger surgical margin may reduce local
      recurrence rate. Although numerous studies have shown effective treatment
      responses after RFA, the precise impact of RFA on survival of colorectal cancer
      patients with liver metastases remains unclear. Resection remains the gold
      standard for patients with liver metastases. In patients with limited number of
      unresectable lesions and in cases, which are unresectable on the basis of
      lesional number and localization, RFA is an attractive approach to obtain tumour
      clearance. Randomised control trials evaluating the value of combined adjuvant
      systemic chemotherapy are still urgently needed.

PMID- 17499500
TI  - Optimization of cold-active protease production by the psychrophilic bacterium
      Colwellia sp. NJ341 with response surface methodology.
AB  - Culture conditions were optimized for an extracellular cold-active protease
      production by the psychrophilic bacterium Colwellia sp. NJ341. Response surface
      methodology was applied for the most significant fermentation parameters (casein,
      citrate sodium, temperature and Tween-80) identified earlier by one-factor-at-a
      time approach. A 2(4) full factorial central composite design was employed to
      determine the maximum protease production. Using this methodology, the quadratic
      regression model of producing cold-active protease was built and the optimal
      combinations of media constituents for maximum protease production (183.21 U/mL)
      were determined as casein 5.18 g/L, citrate sodium 3.84 g/L, temperature 7.96
      degrees C, Tween-80 0.23 g/L. Protease production obtained experimentally
      coincident with the predicted value and the model was proven to be adequate.

PMID- 17499501
TI  - Reduction of organic pollutants in Olive Mill Wastewater by using different
      mineral substrates as adsorbents.
AB  - Physico-chemical treatments of Olive Mill Wastewater (OMW) were carried out using
      different inorganic substrates such as soil, bentonite and zeolite, in order to
      assess their efficiency to remove the organic load from OMW, in particular
      polyphenols (Pp) and to reduce chemical oxygen demand (COD). The effect of
      repeated treatments of OMW with different minerals and the possibility of
      regenerating them by the Low Temperature Ashing (LTA) technique, an eco-friendly
      procedure, for the reutilization of treated OMW, has been investigated. Zeolite
      was found to be highly efficient in adsorbing Pp and COD from OMW and was easy to
      regenerate by means of the LTA technique.

PMID- 17499502
TI  - Investigation of the electro-coagulation treatment process for the removal of
      total suspended solids and turbidity from municipal wastewater.
AB  - In this work, raw municipal wastewater was electro-coagulated for the removal of
      total suspended solids (TSS), turbidity, and particulate BOD using stainless
      steel electrodes. The removal efficiency of TSS and turbidity is shown to depend
      on the amount of iron generated from the anode of the reactive electrode used in
      this study, when applying the lower currents of 0.05 A and 0.1A. For such lower
      currents, the results suggested that the removal is consistent with charge
      neutralization coagulation mechanism. When applying higher currents of 0.2 A, 0.4
      A, and 0.8 A, the results suggested that the dominant removal mechanism is sweep
      floc coagulation as the generated soluble ferrous ions are converted to insoluble
      ferric ions due to oxidation with chlorine generated during the electrochemical
      process at the higher currents. The highest TSS removal efficiency of 95.4%
      occurred at a current of 0.8A and contact time of 5 min. The effect of electro
      coagulation on the removal of particulate BOD was shown to depend on the TSS
      removal efficiency.

PMID- 17499503
TI  - Comparison of the performance of submerged membrane bioreactor (SMBR) and
      submerged membrane adsorption bioreactor (SMABR).
AB  - This study focuses on comparing the performance of submerged membrane bioreactor
      (SMBR) and submerged membrane adsorption bioreactor (SMABR) over a period of 20
      days at a hydraulic retention time (HRT) of 3.1h. The effects of PAC on critical
      flux and membrane fouling were also investigated. The SMABR exhibited better
      results in terms of mixed liquor suspended solids (MLSS) growth, DOC removal
      (over 96%), COD removal (over 95%), transmembrane pressure (TMP) and oxygen
      uptake rate. Nearly 100% of bacteria and 100% of total coliforms were removed in
      both systems. The addition of PAC could maintain the critical flux at a lower TMP
      value (7.5 kPa), while irreversible fouling caused by PAC occurred when the
      filtration flux exceeded critical flux.

PMID- 17499504
TI  - Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene
      indolin-2-ones.
AB  - A novel series of 3-arylureidobenzylidene-indolin-2-ones was synthesized and
      their inhibitory activity against Ret tyrosine kinase investigated in comparison
      with the Ret inhibitor RPI-1 as a reference compound for this series. A few
      compounds were able to revert the RETC634R oncogene-transformed morphologic
      phenotype of NIH3T3(MEN2A) cells and showed a selective antiproliferative
      activity against these cells as compared to parental NIH3T3 cells or NIH3T3 cells
      transformed with a non-tyrosine kinase oncogene (NIH3T3(H-RAS)). Inhibition of
      Ret enzyme activity by effective derivatives was confirmed in a kinase assay.
      Structure-activity relationship indicated a favourable activity for 5,6
      dimethoxyindolinone derivatives with H, OH, or OMe in the para position of the
      distal aryl ring.

PMID- 17499505
TI  - Hit-to-lead studies on benzimidazole inhibitors of ITK: discovery of a novel
      class of kinase inhibitors.
AB  - Benzimidazole 1 was identified as a selective inhibitor of ITK by high throughput
      screening. Hit-to-lead studies defined the SAR at all three substituents.
      Reversing the amide linkage at C6 led to 16, with a fivefold improvement of
      potency. This enhancement is rationalized by the conformational preference of the
      substituent. A model for the binding of the benzimidazoles to the ATP-binding
      site of ITK is proposed.

PMID- 17499506
TI  - Synthesis and radiopharmacological characterization of [11C]AL-438 as a
      nonsteroidal ligand for imaging brain glucocorticoid receptors.
AB  - The radiosynthesis and the radiopharmacological characterization of [(11)C]AL-438
      as a nonsteroidal ligand for the glucocorticoid receptor (GR) is described.
      Radiolabeling of the corresponding desmethyl precursor 10 with [(11)C]MeI gave
      [(11)C]AL-438 in decay-corrected radiochemical yields of 30+/-4% (based upon
      [(11)C]CO(2)) within 35 min at a specific radioactivity of 10-15 GBq/micromol at
      the end-of-synthesis. The radiopharmacological evaluation of [(11)C]AL-438
      involved biodistribution and small animal PET imaging in rats, and
      autoradiography studies using rat brain sections. Biodistribution studies were
      performed in male Wistar rats and demonstrated high radioactivity uptake in
      pituitary and brain. However, the inability of high dose corticosterone to block
      binding would suggest that the radioactivity accumulation in the brain was not
      receptor-mediated.

PMID- 17499508
TI  - Relationship between malignant subtypes of meningioma and clinical outcome.
AB  - We evaluated the relationship between histological malignant subtypes (WHO grade
      II or III) of meningioma and clinical outcome. Of 485 patients treated surgically
      for intracranial meningioma at our hospital between 1994 and 2004, 49 (10%; 18
      male, 31 female) had potentially malignant features. The histological tumor
      subtypes within this group of patients included: atypical (n=23); clear cell
      (n=3); chordoid (n=5); rhabdoid (n=16); and anaplastic (n=4). Correlations among
      prognosis, recurrence, and the following factors were analyzed for each
      histological subtype: the Simpson grade of surgical resection (grades I-III vs.
      grade IV), tumor location (convexity vs. other), the Ki-67 index, and use of
      postoperative radiotherapy. The median value of the Ki-67 index was 16.2% (range:
      1.0-57.2%). The surgical resections were of Simpson grades I-III and IV in 43 and
      six of the 49 patients, respectively. Tumors recurred after the initial surgical
      resection in 14 of the 49 patients. In view of the relatively high proportion of
      malignant subtypes (10%), we suggest that all meningiomas should be evaluated for
      malignancy. The extent of surgical resection, the histological subtype, and the
      Ki-67 index can help to predict the clinical outcome for meningioma patients.

PMID- 17499507
TI  - Directed molecular screening for RecA ATPase inhibitors.
AB  - The roles of bacterial RecA in the evolution and transmission of antibiotic
      resistance genes make it an attractive target for inhibition by small molecules.
      We report two complementary fluorescence-based ATPase assays that were used to
      screen for inhibitors of RecA. We elected to employ the ADP-linked variation of
      the assay, with a Z' factor of 0.83 in 96-well microplates, to assess whether 18
      select compounds could inhibit ATP hydrolysis by RecA. The compounds represented
      five sets of related inhibitor scaffolds, each of which had the potential to
      cross-inhibit RecA. Although nucleotide analogs, known inhibitors of GHL ATPases,
      and known protein kinase inhibitors were not active against RecA, we found that
      three suramin-like agents substantially inhibited RecA's ATPase activity.

PMID- 17499509
TI  - High thoracic spinal infection following upper gastrointestinal work-up.
AB  - Spinal infections originating from the gastrointestinal tract are rare. We report
      a patient in whom esophageal rupture during endoscopy led to spinal infection
      with neurological deficit. An 80-year-old Asian man with a history of recent
      endoscopic gastrointestinal investigation presented to our clinic with the chief
      complaints of upper thoracic discomfort, chest pain and mild intermittent fever.
      Progressive weakness and numbness in both lower extremities had developed during
      the previous two weeks. A thoracic spine MRI showed a space-occupying lesion with
      involvement of the T2 and T3 vertebral bodies including an epidural abscess.
      After surgical decompression, the patient gradually recovered power in his lower
      extremities. Early diagnosis is a key factor to avoid neurologic sequelae in the
      treatment of patients with spinal infection. Physicians need to be aware of this
      potential complication following endoscopic gastrointestinal investigation.

PMID- 17499510
TI  - Bis-pyrene-labeled molecular beacon: a monomer-excimer switching probe for the
      detection of DNA base alteration.
AB  - A new bis-pyrene-labeled oligonucleotide probe (BP-probe) has been designed for
      the detection of a single base mismatch in single strand (ss) DNA as a target.
      The sequence of BP-probe was chosen to form stem-loop structure similar to a
      molecular beacon (MB-probe), yielding bis-pyrene-labeled molecular beacon (BP-MB
      probe). Partially double stranded (ds) BP-MB-probes were prepared by complexation
      with oligonucleotides whose sequences are complementary to the loop segment but
      not to the stem and exchangeable with the target DNA. The partially ds BP-MB
      probes were shown to exhibit monomer fluorescence as major fluorescence, while
      the ss BP-MB-probe in the stem-loop form displays strong excimer fluorescence.
      The strand exchange reactions between partially ds BP-MB-probe and target ss DNA
      in the presence of cationic comb-type copolymer as a catalyst were monitored by
      the excimer fluorescence changes. The existence of a mismatched base can be
      determined by the slower PASE rates compared with fully matched DNA.

PMID- 17499511
TI  - N9-benzyl-substituted 1,3-dimethyl- and 1,3-dipropyl-pyrimido[2,1-f]purinediones:
      synthesis and structure-activity relationships at adenosine A1 and A2A receptors.
AB  - Synthesis and physicochemical properties of N-benzyl pyrimido[2,1-f]purinediones
      are described. These derivatives were synthesized by the cyclization of 7
      chloropropylo-8-bromo-1,3-dimethyl- or 1,3-dipropyl xanthine derivatives with
      corresponding (un)substituted benzylamines. Dipropyl derivatives were obtained
      under microwave irradiation conditions either. The obtained compounds (1-20) were
      evaluated for their affinity to adenosine A1 and A2A receptors, selected
      compounds were additionally investigated for affinity to the A3 receptor subtype.
      The results of the radioligand binding assays to A1 and A2A adenosine receptors
      showed that most of the 1,3-dimethyl-9-benzylpyrimidopurinediones exhibited
      selective affinity to A2A receptors at micromolar or submicromolar concentrations
      (for example, derivative 9 with o-methoxy substituent displayed a Ki value of
      0.699 microM at rat A2A receptor with more than 36-fold selectivity). Contrary to
      previously described arylpyrimido[2,1-f]purinediones dipropyl derivatives
      (compounds 15-20) showed affinity to both kinds of receptors increased, however
      A1 affinity increased to a larger extent, with the result that A2A selectivity
      was abolished. The best adenosine A1 receptor ligand was m-chlorobenzyl
      derivative 18 (Ki=0.089 microM and 5-fold A1 selectivity). Structure-activity
      relationships were discussed with the analysis of lipophilic and spatial
      properties of the investigated compounds. Pharmacophore model of adenosine A1
      receptor antagonist was adopted for this purpose.

PMID- 17499512
TI  - Colon-specific, mutual azo prodrug of 5-aminosalicylic acid with L-tryptophan:
      synthesis, kinetic studies and evaluation of its mitigating effect in
      trinitrobenzenesulfonic acid-induced colitis in rats.
AB  - Mutual azo prodrug of 5-aminosalicylic acid with l-tryptophan was synthesized by
      coupling l-tryptophan with salicylic acid, for targeted drug delivery to the
      inflamed gut tissue in inflammatory bowel disease. The structure of synthesized
      prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro
      kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5
      aminosalicylic acid, whereas in phosphate buffer (pH 7.4) 18% release was
      observed over a period of 7 h. In rat fecal matter, 87.9% of 5-aminosalicylic
      acid was released with a half-life of 143.6 min, following first order kinetics.
      The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold
      stress method. The ameliorating effect of the azo conjugate and therapeutic
      efficacy of the carrier system was evaluated in trinitrobenzenesulfonic acid
      induced experimental colitis model. The synthesized prodrug was found to be
      equally effective in mitigating the colitis in rats as that of sulfasalazine
      without the ulcerogenicity of 5-aminosalicylic acid.

PMID- 17499514
TI  - The armed truce between the intestinal microflora and host mucosal immunity.

PMID- 17499515
TI  - Oral administration of Eclipta alba leaf aqueous extract enhances the non
      specific immune responses and disease resistance of Oreochromis mossambicus.
AB  - Immunostimulatory effects of the oral administration of the medicinal plant,
      Eclipta alba leaf extracts was studied in tilapia, Oreochromis mossambicus. For
      this purpose, fish were fed for 1, 2 or 3 weeks with diets containing E. alba
      leaf aqueous extract at 0, 0.01, 0.1 or 1% levels. After each week, non-specific
      humoral (lysozyme, antiprotease and complement) and cellular (myeloperoxidase
      content, production of reactive oxygen and nitrogen species) responses and
      disease resistance against Aeromonas hydrophila were determined. The results
      indicated that E. alba aqueous extract administered as feed supplement
      significantly enhanced most of the non-specific immune parameters tested. Among
      the humoral responses, lysozyme activity significantly increased after feeding
      with aqueous extract for 1, 2 or 3 weeks. No significant modulation was noticed
      in all the cellular responses tested after 3 weeks of feeding, while reactive
      oxygen species production and myeloperoxidase content showed significant
      enhancement after 1 week of feeding with aqueous extract. When challenged with A.
      hydrophila after 1, 2 or 3 weeks of feeding, the percentage mortality was
      significantly reduced in the treated fish. The highest dose of 1% gave better
      protection than the other doses with the relative percentage survival (RPS)
      values of 64, 75 and 32 after feeding for 1, 2 and 3 weeks respectively. The
      results indicate that dietary intake of E. alba aqueous leaf extract enhances the
      non-specific immune responses and disease resistance of O. mossambicus against A.
      hydrophila.

PMID- 17499516
TI  - Effect of elbow joint angle on force-EMG relationships in human elbow flexor and
      extensor muscles.
AB  - The purpose of this study was to examine the effect of joint angle on the
      relationship between force and electromyogram (EMG) amplitude and median
      frequency, in the biceps, brachioradialis and triceps muscles. Surface EMG were
      measured at eight elbow angles, during isometric flexion and extension at force
      levels from 10% to 100% of maximum voluntary contraction (MVC). Joint angle had a
      significant effect on MVC force, but not on MVC EMG amplitude in all of the
      muscles examined. The median frequency of the biceps and triceps EMG decreased
      with increasing muscle length, possibly due to relative changes in electrode
      position or a decrease in muscle fibre diameter. The relationship between EMG
      amplitude and force, normalised with respect to its maximum force at each angle,
      did not vary with joint angle in the biceps or brachioradialis muscles over all
      angles, or in the triceps between 45 degrees and 120 degrees of flexion. These
      results suggest that the neural excitation level to each muscle is determined by
      the required percentage of available force rather than the absolute force
      required. It is, therefore, recommended that when using surface EMG to estimate
      muscle excitation, force should be normalised with respect to its maximum value
      at each angle.

PMID- 17499513
TI  - Chronic 3,4-dihydroxyphenylalanine treatment induces dyskinesia in aphakia mice,
      a novel genetic model of Parkinson's disease.
AB  - L-DOPA-induced dyskinesia (LID) is one of the main limitations of long term L
      DOPA use in Parkinson's disease (PD) patients. We show that chronic L-DOPA
      treatment induces novel dyskinetic behaviors in aphakia mouse with selective
      nigrostriatal deficit mimicking PD. The stereotypical abnormal involuntary
      movements were induced by dopamine receptor agonists and attenuated by
      antidyskinetic agents. The development of LID was accompanied by preprodynorphin
      and preproenkephalin expression changes in the denervated dorsal striatum.
      Increased FosB-expression was also noted in the dorsal striatum. In addition,
      FosB expression was noted in the pedunculopontine nucleus and the zona incerta,
      structures previously not examined in the setting of LID. The aphakia mouse is a
      novel genetic model with behavioral and biochemical characteristics consistent
      with those of PD dyskinesia and provides a more consistent, convenient, and
      physiologic model than toxic lesion models to study the mechanism of LID and to
      test therapeutic approaches for LID.

PMID- 17499517
TI  - Electromiographic and kinematic characteristics of Kung Fu Yau-Man palm strike.
AB  - A kinematic and electromyographic analysis of Kung Fu (KF) Yau-Man palm strikes
      without impact is presented. An empirical model applied to data obtained by a
      high-speed camera describes the kinematic characteristics of the movement. The
      electromyographic patterns of the biceps brachii, brachioradialis and triceps
      brachii muscles were studied during the strike in the time (root mean square) and
      frequency (wavelet transform) domains. Eight KF practitioners participated in the
      investigation. A wooden board was placed in front of the subjects, and they were
      asked to perform the strike imagining a target above the board. The results show
      that the Yau-Man KF palm strike has very similar kinematic characteristics to a
      simple moderate speed elbow extension movement. All practitioners positioned
      themselves in relation to the wooden board in a way to achieve their highest hand
      speeds in the instant their hands crossed the board. The analyses of the
      electromyography data shows a well developed muscle coordination of the
      practitioners in agreement with kinematic results. The results of this paper are
      important not only for improving the performance of practitioners but also to
      demonstrate the applicability of KF in the process of motor control development.

PMID- 17499518
TI  - Born to adapt, but not in your dreams.
AB  - The brain adapts to changes that take place in the body. Deprivation of input
      results in size reduction of cortical representations, whereas an increase in
      input results in an increase of representational space. Amputation forms one of
      the most dramatic disturbances of the integrity of the body. The brain adapts in
      many ways to this breakdown of the afferent-efferent equilibrium. However, almost
      all studies focus on the sensorimotor consequences. It is not known whether
      adaptation takes place also at other "levels" in the system. The present study
      addresses the question whether amputees dream about their intact body, as before
      the amputation, or about the body after the amputation and whether the dream
      content was a function of time since the amputation and type of amputation. The
      results show that the majority of the dreamers reported dreams about their intact
      body although the mean time that elapsed since the amputation was twelve years.
      There is no clear relation with the type of amputation. The results give modest
      evidence for the existence of a basic neural representation of the body that is,
      at least, partly genetically determined and by this relatively insensitive for
      changes in the sensory input.

PMID- 17499519
TI  - The relationship within and between the extrinsic and intrinsic systems indicated
      by resting state correlational patterns of sensory cortices.
AB  - Much Research has been done on extrinsic and intrinsic systems, which consist of
      brain regions associated with the processing of externally and internally
      oriented stimuli, respectively. However, understanding of the underlying
      relationships within and between these two systems is relatively limited. To
      improve our understanding of these underlying relationships, we investigated the
      positive and negative correlations of three regions of interest (ROIs) located in
      the auditory, visual and somatosensory systems by using resting state functional
      MRI (fMRI) with a large sample size. We found that all three sensory systems
      exhibited significant negative correlation with the intrinsic system. In
      contrast, positive correlations between these sensory cortices and brain regions
      outside their respective system were limited. The present study extended former
      findings by indicating that multiple subsystems rather than a single subsystem of
      the extrinsic system are inherently negatively correlated with the intrinsic
      system. We suggest that these negative correlations between the extrinsic and
      intrinsic systems may explain the phenomenon that externally and internally
      oriented processes can always disturb or even interrupt each other.

PMID- 17499520
TI  - Assignment of functional activations to probabilistic cytoarchitectonic areas
      revisited.
AB  - Probabilistic cytoarchitectonic maps in standard reference space provide a
      powerful tool for the analysis of structure-function relationships in the human
      brain. While these microstructurally defined maps have already been successfully
      used in the analysis of somatosensory, motor or language functions, several
      conceptual issues in the analysis of structure-function relationships still
      demand further clarification. In this paper, we demonstrate the principle
      approaches for anatomical localisation of functional activations based on
      probabilistic cytoarchitectonic maps by exemplary analysis of an anterior
      parietal activation evoked by visual presentation of hand gestures. After
      consideration of the conceptual basis and implementation of volume or local
      maxima labelling, we comment on some potential interpretational difficulties,
      limitations and caveats that could be encountered. Extending and supplementing
      these methods, we then propose a supplementary approach for quantification of
      structure-function correspondences based on distribution analysis. This approach
      relates the cytoarchitectonic probabilities observed at a particular functionally
      defined location to the areal specific null distribution of probabilities across
      the whole brain (i.e., the full probability map). Importantly, this method avoids
      the need for a unique classification of voxels to a single cortical area and may
      increase the comparability between results obtained for different areas.
      Moreover, as distribution-based labelling quantifies the "central tendency" of an
      activation with respect to anatomical areas, it will, in combination with the
      established methods, allow an advanced characterisation of the anatomical
      substrates of functional activations. Finally, the advantages and disadvantages
      of the various methods are discussed, focussing on the question of which approach
      is most appropriate for a particular situation.

PMID- 17499521
TI  - Functional neural dynamics underlying auditory event-related N1 and N1
      suppression response.
AB  - Presenting tone triplets of identical stimuli preceded by silent intervals of 30
      s produces a series of three N1 averaged event-related potentials (ERPs), the
      first being of greater amplitude (non-suppressed N1) than the second and third
      ones (suppressed N1). Maximal statistically independent components (ICs) of
      single-trial multi-electrode scalp EEG responses to triplets were obtained by ICA
      algorithm, and then each IC was searched for underlying brain structures by
      LORETA inverse solution, and for oscillatory contributions by time-frequency
      analysis. Non-suppressed N1 cortical mechanisms were broken down into five ICs,
      grouped in two time-windows (early-onset and late-onset) involving the
      participation of temporal, frontal and parietal structures, and sub-serving EEG
      oscillatory contributions of power enhancement and putative phase concentration
      of mainly theta, alpha and low beta bands. Suppressed N1 was due to the
      modulation of two above-mentioned early-onset ICs, involving temporal structures
      only, and mainly sub-serving oscillatory contributions of phase concentration of
      theta and alpha. Present results, showing quantifiable changes of IC descriptors 
      i.e. time window of activation, implied structures and oscillatory contributions
      - extracted from two distinct brain functional situations (non-suppressed versus
      suppressed N1), give support to the view that ICA is not merely a statistical
      "latent variables" model when applied to ERPs, but could help to capture
      underlying specific function subunits of brain dynamics.

PMID- 17499522
TI  - Fractal dimension and white matter changes in multiple sclerosis.
AB  - The brain white matter (WM) in multiple sclerosis (MS) suffers visible and non
      visible (normal-appearing WM (NAWM)) changes in conventional magnetic resonance
      (MR) images. The fractal dimension (FD) is a quantitative parameter that
      characterizes the morphometric variability of a complex object. Our aim was to
      assess the usefulness of FD analysis in the measurement of WM abnormalities in
      conventional MR images in patients with MS, particularly to detect NAWM changes.
      First, we took on a voxel-based morphometry approach optimized for MS to obtain
      the segmented brain. Then, the FD of the whole grey-white matter interface (WM
      border) and skeletonized WM was calculated in patients with MS and healthy
      controls. To assess the FD of the NAWM, we focused our analysis on single
      sections without lesions at the centrum semiovale level. We found that patients
      with MS had a significant decrease in the FD of the entire brain WM compared with
      healthy controls. Such a decrease of the FD was detected not only on MR image
      sections with MS lesions but also on single sections with NAWM. Taken together,
      the results showed that FD identifies changes in the brain of patients with MS,
      including in NAWM, even at an early phase of the disease. Thus, FD might become a
      useful marker of diffuse damage of the central nervous system in MS.

PMID- 17499523
TI  - Morphing the body: illusory feeling of an elongated arm affects somatosensory
      homunculus.
AB  - Recent studies suggest that in contrast to traditional views of the body map the
      topographic representation in primary somatosensory cortex (SI) reflects the
      perceived rather than the physical aspects of peripheral stimulation. Here, we
      created a simple illusion of feeling an elongated arm by using the dominance of
      the visual domain over the tactile sense: employing an artificial hand and arm,
      which were connected to the body, subjects were given the visual impression that
      they had an extended arm. Since it is known from animal studies that tactile
      illusions alter early sensory processing in SI, we expected a modulation of the
      topography in SI corresponding to this illusion. Behavioral results showed that
      during the illusion the participants felt that their arm was elongated.
      Neuromagnetic source imaging of the functional organization in SI revealed that
      the cortical distance between first (D1) and fifth digit (D5) decreased when
      subjects felt the arm elongated. Since this modulation was significantly
      positively correlated with the illusionary feeling of an extended arm, the
      results suggest an involvement of SI during perceived changes in the size of body
      parts. We discuss the results as possible top-down modulations of SI by higher
      order somatosensory areas.

PMID- 17499524
TI  - Sex differences in regional gray matter in healthy individuals aged 44-48 years:
      a voxel-based morphometric study.
AB  - The study examined sex-related differences in regional gray matter (GM) in 44-48
      year old healthy individuals. T1-weighted MRI scans were acquired in 411 subjects
      aged 44-48 from a random community sample and optimized voxel-based morphometry
      was applied to detect regional GM difference between men and women, correcting
      for effects of age, years of education, handedness, and total intracranial volume
      (TIV). Men had larger brain volumes and higher white matter (WM) to TIV ratios
      compared with women. Women had higher GM to TIV ratios than men. After
      controlling for age, years of education, handedness, and TIV, there were no
      significant differences between men and women in the total GM volumes. Regional
      sex dimorphism was present, with men having more GM volume in midbrain, left
      inferior temporal gyrus, right occipital lingual gyrus, right middle temporal
      gyrus, and both cerebellar hemispheres. Women showed more GM in dorsal anterior,
      posterior and ventral cingulate cortices, and right inferior parietal lobule. Our
      results suggest sex dimorphism in GM in middle aged healthy individuals, which is
      not likely to be explained by brain pathology. These differences may provide the
      structural brain basis for sex differences in certain cognitive functions.

PMID- 17499525
TI  - Test-retest reliability of fMRI activation during prosaccades and antisaccades.
AB  - Various studies have investigated reproducibility of fMRI results. Whereas group
      results can be highly reproducible, individual activity maps tend to vary across
      sessions. Individual reliability is of importance for the application of fMRI in
      endophenotype research, where brain activity is linked to genetic polymorphisms.
      In this study, the test-retest reliability of activation maps during the
      antisaccade paradigm was assessed for individual and group results. Functional
      MRI images were acquired during two sessions of prosaccades and antisaccades in
      twelve healthy subjects using an event-related fMRI design. Reliability was
      assessed for both individual and group-wise results. In addition, the reliability
      of differences between subjects was established in predefined regions of
      interest. The reliability of group activation maps was high for prosaccades and
      antisaccades, but only moderate for antisaccades vs. prosaccades, probably as a
      result of low statistical power of individual results. Reproducibility of
      individual subject maps was highly variable, indicating that reliable results can
      be obtained in some but not all subjects. Reliability of individual activity maps
      was largely explained by individual differences in the global temporal signal to
      noise ratio (SNR). As the global SNR was stable over sessions, it explained a
      large portion of the differences between subjects in regional brain activation. A
      low SNR in some subjects may be dealt with either by improving the statistical
      sensitivity of the fMRI procedure or by subject exclusion. Differences in the
      global SNR between subjects should be addressed before using regional brain
      activation as phenotype in genetic studies.

PMID- 17499526
TI  - Endodontic and periodontal treatment of an external cervical resorption.
AB  - External root resorption can be divided into 3 categories: 1) progressive
      inflammatory resorption; 2) cervical resorption; and 3) replacement resorption.
      Cervical resorption is a not well recognized type of progressive external
      inflammatory resorption. It occurs after injury to the cervical attachment
      apparatus, mostly in the area of the cervical root surface (precementum) below
      the epithelial attachment. The present article describes an abnormal case of
      cervical resorption in a vital lateral maxillary incisor of a 27-year-old male
      patient. Endodontic treatment and subsequent periodontal plastic-esthetic surgery
      were performed. Reconstruction of the defect was achieved using mineral trioxide
      aggregate cement. After 2 years, the tooth showed no pathologic symptoms. The
      present case demonstrates a novel combined endodontic and periodontal treatment
      of an external root resorption.

PMID- 17499527
TI  - Nonsurgical endodontic treatments in molar teeth with large periapical lesions in
      children: 2-year follow-up.
AB  - Profound caries lesions may lead to invasion of microorganisms to the dental
      pulp, and periapical areas can promote the development of dentoalveolar abscess
      and periapical bone loss. Treatment options to manage large periapical lesions
      range from nonsurgical root canal treatment and/or apical surgical procedure to
      extraction. Young molar teeth with pulp necrosis and large periapical lesions in
      children are frequently treated with root canal treatment because the therapy is
      more difficult in multirooted teeth. In these case reports, nonsurgical
      endodontic treatments performed on 6 molar teeth with large periapical lesions,
      by repeated intracanal dressing with calcium hydroxide, are presented.
      Radiographs displayed significant bony healing at the end of the second year. In
      conclusion, large periapical lesions can respond favorably to nonsurgical
      treatment, and complex and difficult endodontic treatments in children might not
      be required.

PMID- 17499528
TI  - Bacteriologic investigation of the effects of sodium hypochlorite and
      chlorhexidine during the endodontic treatment of teeth with apical periodontitis.
AB  - OBJECTIVE: This clinical study was undertaken to compare the effectiveness of
      2.5% sodium hypochlorite (NaOCl) and 0.12% chlorhexidine digluconate as irrigants
      in reducing the cultivable bacterial populations in infected root canals of teeth
      with apical periodontitis. STUDY DESIGN: According to stringent
      inclusion/exclusion criteria, 32 teeth with primary intraradicular infections and
      chronic apical periodontitis were selected and followed in the study. Bacterial
      samples were taken at the baseline (S1) and after chemomechanical preparation
      using either NaOCl (n = 16) or chlorhexidine (n = 16) as irrigants (S2).
      Cultivable bacteria recovered from infected root canals at the 2 stages were
      counted. Isolates from S2 samples were identified by means of 16S rRNA gene
      sequencing analysis. RESULTS: At S1, all canals were positive for bacteria, and
      the median number of bacteria per canal was 7.32 x 10(5) for the NaOCl group and
      8.5 x 10(5) for the chlorhexidine group. At S2, the median number of bacteria in
      canals irrigated with NaOCl and chlorhexidine was 2.35 x 10(3) and 2 x 10(2),
      respectively. Six of 16 (37.5%) canals from the NaOCl group and 8 of 16 (50%)
      canals from the chlorhexidine group yielded negative cultures. Chemomechanical
      preparation using either solution substantially reduced the number of cultivable
      bacteria in the canals. No significant difference was observed between the NaOCl
      and chlorhexidine groups with regard to the number of cases yielding negative
      cultures (P = .72) or quantitative bacterial reduction (P = .609). The groups
      irrigated with NaOCl or chlorhexidine showed a mean number of 1.3 and 1.9
      cultivable species per canal, respectively. The great majority of isolates in S2
      were from gram-positive bacteria, with streptococci as the most prevalent taxa.
      CONCLUSIONS: The present findings revealed no significant difference when
      comparing the antibacterial effects of 2.5% NaOCl and 0.12% chlorhexidine used as
      irrigants during the treatment of infected canals.

PMID- 17499529
TI  - Blindness and basal ganglia hypoxia as a complication of Le Fort I osteotomy
      attributable to hypoplasia of the internal carotid artery: a case report.
AB  - Le Fort I osteotomy is used as a surgical procedure for correction of
      maxillofacial deformities. The common complications of this procedure are
      hemorrhage and infection, with incidence of 6% to 9%. Blindness associated with
      Le Fort I osteotomy was reported in 8 patients. An 18-year-old female complained
      of loss of sight in the left eye after recovery from hypotensive general
      anesthesia. The visual field of the left eye was dark and only perceived some
      movement. She presented with motor dysfunction and regressive behavior 2 weeks
      later as a result of hypoxia of bilateral basal ganglia. Two months later, her
      visual acuity recovered gradually and regressive behavior improved. Carotid
      angiography showed congenital hypoplasia of the left internal carotid artery. We
      suspected that hypoplasia could cause hypoxia of the central nervous system.

PMID- 17499530
TI  - Calcium and hydroxide release from different pulp-capping materials.
AB  - OBJECTIVE: To evaluate the release of calcium and hydroxide ions from the pulp
      capping materials Hydro C, NuCap, Life, and Ultrablend Plus. STUDY DESIGN: The
      materials were manipulated and inserted into tubes measuring 1 cm in length and 1
      mm in diameter. The filled tubes were individually immersed in flasks containing
      10 mL deionized water. The tubes were removed from the flasks after 3, 24, 72,
      and 168 hours, and the release of hydroxide and calcium ions was measured with a
      pH-meter and an atomic absorption spectrophotometer, respectively. The data were
      compared by analysis of variance and Tukey test. RESULTS: The results showed that
      Ultrablend Plus provided the greatest release of calcium ions, with a significant
      difference observed between Life and Ultrablend after 3 hours. Evaluation after
      24, 72, and 168 hours showed a significant difference between Ultrablend and the
      other materials. No hydroxide release was observed from the Ultrablend cement at
      any time period. After 3 hours, significant differences were observed between
      Hydro C and the Life and Ultrablend materials and between NuCap and the Life and
      Ultrablend materials. After 24 hours, significant differences were observed
      between the NuCap agent and the other materials. After 72 hours, a significant
      difference was noted only between NuCap and Ultrablend, whereas after 168 hours a
      significant difference was observed between NuCap and the Hydro C and Ultrablend
      materials. CONCLUSION: All materials released calcium and hydroxide ions, except
      Ultrablend Plus which did not show any release of hydroxide ions.

PMID- 17499531
TI  - Intraoral endoscopically assisted treatment of temporomandibular joint ankylosis:
      preliminary report.
AB  - Temporomandibular joint (TMJ) ankylosis is characterized by the formation of a
      bony or fibrous mass that replaces the normal articulation. To avoid a possible
      re-ankylosis it is mandatory to perform a radical, complete resection of the
      bony/fibrous mass. We treated a patient affected by right temporomandibular joint
      ankylosis performing the osteotomy of the ankylotic mass through a preauricular
      and intraoral approach under endoscopic control. Then a temporalis muscle and
      fascia flap were used as the interpositional material. Through the endoscope it
      was easy to check the medial aspect of the resection and suture the flap. At 1
      year follow-up the patient had significantly increased maximal mouth opening. No
      evidence of relapse of the joint ankylosis was shown by radiological studies.
      Intraoral endoscopic assistance may be useful to make the removal of the
      ankylotic mass safer, and the anchorage of the temporalis muscle and fascia flap
      more accurate, reducing the risk of re-ankylosis.

PMID- 17499532
TI  - Findings on low-field cranial MR images in epileptic dogs that lack interictal
      neurological deficits.
AB  - Recurrent seizuring is a common neurological problem in dogs and can present
      diagnostic difficulties for the attending clinician. Associated interictal
      neurological deficits strongly suggest brain disease but the frequency of
      structural abnormalities in patients without such deficits is unknown. In this
      study the prevalence of clinically significant magnetic resonance imaging (MRI)
      abnormalities was determined in two groups of interictally normal dogs, those
      younger than 6 years and those older than 6 years of age. In the former group,
      only 1/46 dogs (2.2%) had significant MRI abnormalities, whereas in the latter
      group, 8/30 (26.7%) were abnormal. None of the dogs had an identifiable metabolic
      cause for the seizures. These findings suggest that the diagnostic yield of
      advanced neuroimaging techniques in young seizuring dogs without interictal
      neurological deficits is low, but reaffirms their value in similar older
      individuals.

PMID- 17499533
TI  - Evidence of low molecular weight components in the organic matrix of the reef
      building coral, Stylophora pistillata.
AB  - Biominerals contain both inorganic and organic components. Organic components are
      collectively termed the organic matrix, and this matrix has been reported to play
      a crucial role in mineralization. Several matrix proteins have been characterized
      in vertebrates, but only a few in invertebrates, primarily in Molluscs and
      Echinoderms. Methods classically used to extract organic matrix proteins
      eliminate potential low molecular weight matrix components, since cut-offs
      ranging from 3.5 to 10 kDa are used to desalt matrix extracts. Consequently, the
      presence of such components remains unknown and these are never subjected to
      further analyses. In the present study, we have used microcolonies from the
      Scleractinian coral Stylophora pistillata to study newly synthesized matrix
      components by labelling them with 14C-labelled amino acids. Radioactive matrix
      components were investigated by a method in which both total organic matrix and
      fractions of matrix below and above 5 kDa were analyzed. Using this method and
      SDS-PAGE analyses, we were able to detect the presence of low molecular mass
      matrix components (<3.5 kDa), but no free amino acids in the skeletal organic
      matrix. Since more than 98% of the 14C-labelled amino acids were incorporated
      into low molecular weight molecules, these probably form the bulk of newly
      synthesized organic matrix components. Our results suggest that these low
      molecular weight components may be peptides, which can be involved in the
      regulation of coral skeleton mineralization.

PMID- 17499534
TI  - Ganglioside from eel serum high density lipoprotein (HDL) and its role as a
      ligand for HDL binding protein.
AB  - First, we attempted to isolate glycosphingolipids from eel serum HDL. A single
      ganglioside containing N-acetylneuraminic acid (NeuAc), which is positive with
      resorcinol and orcinol reactions, was purified. The mobilities of the purified
      ganglioside and its lyso-form on high performance TLC were similar as those of
      authentic GM4 and its lyso-form, respectively. The mass of the purified
      ganglioside was determined by TOF mass spectrometer, and the mass of its
      oligosaccharide was the same as that of authentic GM4 from human brain consisting
      of disaccharide of NeuAc and galactose. The ganglioside from eel HDL was not
      hydrolyzed by recombinant endoglycoceramidase II, which cannot hydrolyze between
      galactose and ceramide of gangliosides, but hydrolyzes between glucose and
      ceramide. We concluded from these results that the ganglioside purified from eel
      serum HDL is GM4. Second, we investigated the effects of the ganglioside on
      binding of HDL labeled with fluorescein isothiocyanate (FITC-HDL) to cultured eel
      hepatocytes and on FITC-HDL ligand blotting by using plasma membrane proteins of
      the hepatocytes. Stimulatory effect of GM4 on FITC-HDL binding to the hepatocytes
      and FITC-HDL ligand blotting suggests strongly that GM4 is a ligand for HDL
      binding protein of eel hepatocytes.

PMID- 17499535
TI  - Biosynthesis and functions of eicosanoids generated by the coelomocytes of the
      starfish, Asterias rubens.
AB  - Eicosanoids are a group of oxygenated fatty acid derivatives formed from C20
      polyunsaturated fatty acids, including arachidonic and eicosapentaenoic acids.
      The potential of the coelomocytes of the starfish, Asterias rubens, to generate
      eicosanoids through the cyclooxygenase (COX) and lipoxygenase (LOX) pathways was
      investigated using reverse-phase high performance liquid chromatography, enzyme
      immunoassay and gas chromatography-mass spectrometry. The principal LOX product
      was identified as 8-hydroxyeicosatetraenoic acid (8-HETE) with 8
      hydroxyeicosapentaenoic acid (8-HEPE) synthesised at significantly lower levels.
      No classical prostaglandins (PG), such as PGE2 or PGD2, were found to be
      generated by ionophore-challenged coelomocytes. Incubation of coelomocytes with
      lipopolysaccharides from either Escherichia coli or Salmonella abortus failed to
      induce an increase in generation of LOX products and the presence of 8-HETE (0-25
      microM) had no significant effect on the in vitro phagocytic activity of Asterias
      coelomocytes. Neither indomethacin (a COX inhibitor) or esculetin (a LOX
      inhibitor) had any effect on the clearance of the bacterium, Vibrio splendidus,
      from the coelomic cavity of starfish suggesting that products of these enzymes
      are not involved in such coelomocyte responses to foreign particles.

PMID- 17499536
TI  - [The risk of prion contamination through the transfusion of cellular products].
AB  - Since the publication of observations of variant Creutzfeld-Jacob disease (vCJD)
      having occurred in the UK due to transfusion of infected packed red cells, the
      risk of vCJD transmission by blood transfusion is established. In France, no such
      case has yet been reported, but among the French vCJD cases observed, three
      individuals, having entered the disease in 2004, are past blood donors. Thus,
      some individuals transfused in their past are at risk of developing a vCJD. The
      lack of available assay prevents the diagnosis of the infection in these
      recipients and the implementation of a specific screening of blood donations. In
      the UK and in France, several measures to ensure transfusion safety have been
      applied to reduce the risk of contamination by the variant.

PMID- 17499537
TI  - [Iron deficiency anaemia: clinical presentation, biological diagnosis and
      management].
AB  - The iron deficiency is the first cause of anaemia. In healthy young adult, anemia
      is well tolerated because of its progressive installation. The most common
      symptoms of anemia are pallor, fatigue and dyspnea. In biological exams, anemia
      is classically associated with microcytosis and hypochromia. The origins of
      microcytic anemia are iron deficiency, inflammatory aetiologies, thalassemia and
      sideroblastic anaemia. The iron-deficiency diagnosis includes two explorations:
      biological and clinical. The biological exploration is based on interpretation of
      serum biologics tests as blood iron, ferritin, transferrin with saturation, total
      iron-binding capacity and its soluble receptors. This interpretation is simple if
      it is not associated with clinical disorders influencing the internal iron cycle.
      The clinical exploration must always be followed by a careful assessment of the
      underlying cause as blood loss. The most common causes in women of reproductive
      age are gynaecologic. In men and menopausal women, the gastrointestinal tract
      bleeding is source of anemia. Therapeutic management of anemia is oral iron
      therapy. Etiological diagnostic of microcytosis is essential before iron therapy.
      If not, the treatment could be inefficient or it could mask or delay the
      etiological diagnostic.

PMID- 17499538
TI  - [Platelets cytokines and their effects on platelet transfusion].
AB  - Platelets have long been confined to haemostasis only. However, novel functions
      for platelets have been identified recently. Those non-nucleated cells indeed
      participate to inflammation and also they produce and release numerous factors
      with known immunomodulatory functions. Among those factors are cytokines and
      chemokines and the like, such as soluble CD40-Ligand (CD154), which are key
      molecules in that they bridge innate and adaptative immunity; sCD40L is active on
      T cells, B cells, monocytes and macrophages, dendritic cells and endothelial
      cells lining the blood vessels. This means that when a platelet concentrate is
      transfused to a recipient, a huge amount of cytokines and chemokines is also
      infused. In this state of the art review, we will present arguments on the role
      of platelet secretory products in modulating cellular parameters of immunity, and
      -very likely--in altering functions of those immune cells upon encounters while
      infusing platelets in blood recipients. We aimed at summarizing data that have
      been made available on the issue of cytokines/chemokines released by stored
      platelets prior to delivery. We will focus on the suspected role of the
      CD40/CD40L tandem in postplatelet transfusion reactions or incidents. We will
      present recent data on the role of pathogen inactivators on the docking and/or
      release of cytokines/chemokines by platelets.

PMID- 17499539
TI  - [Plasma fractionation in the world: current status].
AB  - From 22 to 25 million liters of plasma are fractionated yearly in about 70
      fractionation plants, either private or government-owned, mainly located in
      industrialized countries, and with a capacity ranging from 50000 to three million
      liters. In an increasingly global environment, the plasma industry has recently
      gone through a major consolidation phase that has seen mergers and acquisitions,
      and has led to the closure of a number of small plants in Europe. Currently, some
      fifteen countries are involved into contract plasma fractionation programs to
      ensure a supply of plasma-derived medicinal products. The majority of the plasma
      for fractionation is obtained by automated plasmapheresis, the remaining
      (recovered plasma) being prepared from whole blood as a by-product of red cell
      production. Plasma for fractionation should be produced, and controlled following
      well established procedures to meet the strict quality requirements set by
      regulatory authorities and fractionators. The plasma fractionation technology
      still relies heavily on the cold ethanol fractionation process, but has been
      improved by the introduction of modern chromatographic purification methods, and
      efficient viral inactivation and removal treatments, ensuring quality and safety
      to a large portfolio of fractionated plasma products. The safety of these
      products with regards to the risk of transmission of variant Creutzfeldt-Jakob
      disease seems to be provided, based on current scientific data, by extensive
      removal of the infectious agent during certain fractionation steps. The leading
      plasma product is now the intravenous immunoglobulin G, which has replaced factor
      VIII and albumin in this role. The supply of plasma products (most specifically
      coagulation products and immunoglobulin) at an affordable price and in sufficient
      quantity remains an issue; the problem is particularly acute in developing
      countries, as the switch to recombinant factor VIII in rich countries has not
      solved the supply issue and has even led to an increase of the mean price of
      plasma-derived factor VIII to the developing world. In the last few years, the
      plasma fractionation industry has improved greatly, and should remain essential
      in the years to come for the procurement of many essential medicines.

PMID- 17499540
TI  - Relationship between the hyperinsulinemic-euglycaemic clamp and a new simple
      index assessing insulin sensitivity in overweight and obese postmenopausal women.
AB  - OBJECTIVE: The purpose of this study was to compare assessment of insulin
      sensitivity from hyperinsulinemic euglycaemic (HIEG) clamp with indexes derived
      from fasting and oral glucose tolerance test (OGTT). SUBJECTS AND METHODS: Cross
      sectional study with 107 sedentary non-diabetic overweight and obese
      postmenopausal (BMI=32.4+/-0.4 kg/m(2)) women undergoing both HIEG clamp and
      OGTT. Pairs of data were analyzed using Pearson correlation and Bland-Altman
      graphs analysis. Comparison between correlations was made using the method
      reported by Zar. RESULTS: All the indexes derived from either the OGTT or
      surrogate indexes were highly correlated with all the clamp-derived formulas
      (P<0.0001). However, HOMA and QUICKI were generally less correlated than OGTT
      derived indexes. Analogically to QUICKI, we calculated a new formula derived from
      the OGTT measurements of glucose and insulin named simple index assessing insulin
      sensitivity (SI(is)OGTT)=1/[log(sum glucose t(0-30-90-120)) (mmol/l)+log(sum
      insulin t(0-30-90-120)) (microUI/ml)]. By using this formula, we found high
      significant correlations (r's=0.61-0.65; P<0.0001) with the clamp results.
      Moreover, the correlations of SI(is)OGTT with the clamp data were higher than for
      other previously published indexes. CONCLUSION: In that large group of non
      diabetic overweight and obese postmenopausal women insulin sensitivity index
      derived from OGTT provided more accurate information than fasting based formula.
      We propose a new simple index for the assessment of insulin sensitivity from the
      OGTT data (SI(is)OGTT). The advantage of this new formula over all previously
      published OGTT-derived indexes of insulin sensitivity is that it is 1) easy to
      calculate 2) better correlated than other indexes of insulin sensitivity and 3)
      not affected by the way clamp results are expressed. Further studies are needed
      to validate SI(is)OGTT index in other populations.

PMID- 17499541
TI  - Antihyperglycaemic treatment of type 2 diabetes: results from a national diabetes
      register.
AB  - AIM: To describe clinical characteristics and antihyperglycemic treatment
      patterns in patients with varying duration of diabetes. METHODS: We performed a
      cross-sectional survey of 61890 type 2 diabetic (DM2) patients from the Swedish
      National Diabetes Register (NDR) in 2004. We also analysed the effect of types of
      treatment and risk factors on glycaemic control in a longitudinal cohort study
      from 1996 to 2004. HbA(1c), risk factors and treatments were determined locally
      in primary care as well as hospital outpatient clinics. RESULTS: Insulin was
      frequently used in DM2 patients with long duration of diabetes, although the mean
      HbA(1c) increased and only a few in this group reached HbA(1c) <7.0%. Patients
      showing long-term improvement in HbA(1c) (>1%) from 1996 to 2004 were more often
      treated with insulin than with oral hypoglycaemic agents (OHA). During this
      period, the HbA(1c) levels leading to additional treatment decreased. A low BMI,
      decreasing BMI and not smoking were predictors of good long-term metabolic
      control. Hypertension and hyperlipidaemia were frequent in both newly diagnosed
      DM2 patients and in patients with a long duration of diabetes. CONCLUSIONS:
      Insulin treatment was frequently used, particularly in patients with a long
      duration of DM2. The glycaemic control, which usually deteriorates over time, did
      not reach the recommended goal, despite the fact that complementary treatment was
      added at lower HbA(1c) levels in 2003 than in 1996. High frequencies of
      hypertension, hyperlipidaemia and high 10-year risks of coronary heart disease
      necessitate intensified risk factor control in the future.

PMID- 17499542
TI  - Disadvantaged mothers, young children and smoking in the home: mothers' use of
      space within their homes.
AB  - Breathing tobacco smoke is linked to poor health in young children, with their
      homes identified as the primary place of exposure. This UK study uses focus group
      discussions to explore how mothers living in disadvantaged areas use space within
      their homes to smoke while looking after children aged 0-4 years, and critically
      examines how they define non-smoking or smoking homes. Many women imposed
      temporary and ad hoc restrictions, and this research highlights how the mothers'
      desire to create a smoke-free environment for their children competes with their
      caring responsibilities, and how their efforts are restricted by the limitations
      of the physical environment of their homes.

PMID- 17499543
TI  - Two DNAzymes targeting the telomerase mRNA with large difference in Mg2+
      concentration for maximal catalytic activity.
AB  - The 10-23 RNA-cleaving DNAzymes require divalent metal ions, preferentially
      Mg(2+), for catalytic activity. For intracellular applications, it is important
      that a DNAzyme can perform maximal cleavage at physiological concentration of
      Mg(2+) (0.2-2mM). We designed DNAzymes targeting the mRNA of human telomere
      reverse transcriptase, two of them turned out to have large difference in Mg(2+)
      concentration requirement (1mM vs. 20mM) for maximal activity in vitro. When the
      two DNAzymes were transfected into HeLa cells, only the one requiring low Mg(2+)
      concentration showed inhibitory activity indicating that the in vitro property
      regarding Mg(2+) requirement was reserved in vivo. The cleavage of target RNA
      mainly involves two processes, that is hybridization of DNAzyme with substrate
      and cleavage of substrate in the DNAzyme-substrate duplex. To explore how the
      optimal Mg(2+) concentration was determined, we studied the effect of Mg(2+) on
      the two processes. For both DNAzymes, Mg(2+) enhanced hybridization over a range
      of concentration far beyond 1mM. Once the DNAzymes hybridized with their 19-mer
      substrates without flanking sequences, the cleavages showed little difference in
      Mg(2+) concentration-dependence. These facts suggest that the flanking sequences
      played a key role in determining the Mg(2+) concentration for maximal DNAzyme
      activity possibly via the formation of higher order structure in the DNAzyme
      substrate duplex.

PMID- 17499544
TI  - Pluripotent versus totipotent plant stem cells: dependence versus autonomy?
AB  - Little is known of the mechanisms that induce the dedifferentiation of a single
      somatic cell into a totipotent embryogenic cell that can either be regenerated or
      develop into an embryo and subsequently an entire plant. In this Opinion article,
      we examine the cellular, physiological and molecular similarities and differences
      between different plant stem cell types. We propose to extend the plant stem cell
      concept to include single embryogenic cells as a totipotent stem cell based on
      their capacity to regenerate or develop into an embryo under certain conditions.
      Our survey suggests that differences in chromatin structure might ensure that
      meristem-localized stem cells have supervised freedom and are pluripotent, and
      that embryogenic stem cells are unsupervised, autonomous and, hence, freely
      totipotent.

PMID- 17499545
TI  - The new set-up of the medical informatics Master of Science program at the
      University of Amsterdam.
AB  - OBJECTIVES: To describe the new set-up of our Master of Science program in
      medical informatics that started in September 2006 at the University of Amsterdam
      Academic Medical Center, The Netherlands. METHODS: To harmonize with the Bologna
      declaration, we transformed our former medical informatics program from a 4-year
      course into a 3-year bachelor and a 2-year (English) Master of Science Medical
      Informatics program. We describe the objectives, organizational structure and
      contents of this new medical informatics master program. RESULTS: The new master
      program now is aimed at (international) baccalaureates in medical informatics,
      computer science, medicine and other health-related studies and professionals
      from these disciplines. The master course comprises four study semesters of 30 EC
      each, equal to 120 EC in total. Central to the program is the context of hospital
      organization, encompassing medical practice and patient care, information and
      communication technologies and (logistic) structuring of health care and health
      care processes. The program comprises core education (60 EC), discipline-related
      in-depth-study (12 EC) and an academic work placement (48 EC). Students from a
      range of other disciplines will be admitted to the master program after
      successful completion of an individualized conversion program (a maximum of 30
      EC). CONCLUSIONS: With the new set-up of our master course and by offering
      individualized conversion programs, we hope to both accommodate the learning
      needs of our own medical informatics baccalaureates and to attract other
      (international) students and professionals to our new program. Our ultimate aim
      is to bring forth medical informatics specialists who can make significant
      contributions to the field.

PMID- 17499546
TI  - Severe influenza resembling hemorrhagic shock and encephalopathy syndrome.
AB  - Influenza-associated encephalopathy is a clinically diverse syndrome and severe
      cases are not well documented outside Japan. Clinical, pathological and molecular
      aspects are described of two fatal cases presenting during 2004 and 2005 winter
      seasons in The Netherlands. Results showed that severe influenza can resemble
      hemorrhagic shock and encephalopathy syndrome, and proper testing for influenza
      virus should be considered in similar cases. The failure to detect viral
      replication in non-pulmonary organs including the brain would support the
      pathogenesis of this syndrome is based on proinflammatory cytokine responses.

PMID- 17499547
TI  - Unusual mitochondrial genome structures throughout the Euglenozoa.
AB  - Mitochondrial DNA of Kinetoplastea is composed of different chromosomes, the
      maxicircle (bearing 'regular' genes) and numerous minicircles (specifying guide
      RNAs involved in RNA editing). In trypanosomes [Kinetoplastea], DNA circles are
      compacted into a single dense body, the kinetoplast. This report addresses the
      question whether multi-chromosome mitochondrial genomes and compacted chromosome
      organization are restricted to Kinetoplastea or rather occur throughout
      Euglenozoa, i.e., Kinetoplastea, Euglenida and Diplonemea. To this end, we
      investigated the diplonemid Rhynchopus euleeides and the euglenids Petalomonas
      cantuscygni, Peranema trichophorum and Entosiphon sulcatum, using light and
      electron microscopy and molecular techniques. Our findings together with
      previously published data show that multi-chromosome mitochondrial genomes
      prevail across Euglenozoa, while kinetoplast-like mtDNA packaging is confined to
      trypanosomes.

PMID- 17499549
TI  - Identification of specific sequence motifs in the upstream region of 242 human
      miRNA genes.
AB  - We have identified novel over-represented and conserved motifs in the upstream
      regions of human and mouse miRNA stem-loop sequences by means of a new
      bioinformatic processing regimen. We observed sequence conservation -500 bp
      upstream in 189 human and mouse miRNAs declining with increasing distance from
      their putative miRNA stem-loop origin. We also found relatively GC-rich regions
      having more than 50% of guanine+cytosine (G+C) content at about -30 and -170 bp
      relative to human miRNA stem-loop sequence origin. To further identify specific
      sequence motifs that might be involved in the transcriptional regulation of miRNA
      precursors, we first searched 500 bp upstream sequences of 194 non-redundant
      human miRNA stem-loop sequences for frequently occurring motifs 5-15 bp long. We
      then found the comparable occurrences of the 20 most frequent motifs in the 2000
      bp upstream regions of 242 human and 290 mouse miRNAs. The significantly reduced
      frequency of occurrence of all 20 motifs in the regions 2000 bp upstream of
      23,570 human RefSeq genes demonstrated that these motifs were specific to the
      upstream miRNA sequences. The most frequently observed motif M1
      (GTGCTTMTAGTGCAG), with a MEME E-value of 3.8e-57 was distributed within 500 bp
      upstream of stem-loop sequences and was also miRNA-specific. We suggest that
      these over-represented motif sites are good candidates for experimentally testing
      miRNA expression as well as possible interaction with regulatory factors.

PMID- 17499548
TI  - A new protocol of analyzing isotope-coded affinity tag data from high-resolution
      LC-MS spectrometry.
AB  - Isotope-coded affinity tags (ICAT) is a labeling technique that provides insights
      into quantitative molecular changes. In this paper, we propose a new protocol to
      identify and analyze ICAT labeled peak pairs in high-resolution LC-MS data. Our
      major contributions are: (1) we use isotope distance constraint, ICAT distance
      constraint, and LC-span constraint to identify ICAT labeled peak pairs and (2) we
      propose to trigger tandem MS/MS scanning based on the ratio estimation value of
      identified ICAT peak pairs instead of the peak intensity values. Compared with
      current approaches that choose peaks with high intensity values for tandem MS/MS
      scanning, the new protocol can improve the scanning efficiency and accuracy.

PMID- 17499550
TI  - Improving the power to detect differentially expressed genes in comparative
      microarray experiments by including information from self-self hybridizations.
AB  - Our ability to detect differentially expressed genes in a microarray experiment
      can be hampered when the number of biological samples of interest is limited. In
      this situation, we propose the use of information from self-self hybridizations
      to acuminate our inference of differential expression. A unified modelling
      strategy is developed to allow better estimation of the error variance. This
      principle is similar to the use of a pooled variance estimate in the two-sample t
      test. The results from real dataset examples suggest that we can detect more
      genes that are differentially expressed in the combined models. Our simulation
      study provides evidence that this method increases sensitivity compared to using
      the information from comparative hybridizations alone, given the same control for
      false discovery rate. The largest increase in sensitivity occurs when the amount
      of information in the comparative hybridization is limited.

PMID- 17499551
TI  - Hepatitis C virus contact map prediction based on binary encoding strategy.
AB  - Inter-residue contact map is an important two-dimensional representation of
      protein spatial structure, and has much potential application in the area of
      understanding protein fold mechanism. In the present note, a 19-bit binary input
      encoding strategy, integrating with residue pair conformational features
      (possible residue pairwise, residue classification, secondary structure, sequence
      length, and sequence separation information), is proposed for the purpose of
      capturing mapping relationship of protein sequence. Simulation results on a set
      of 61 hepatitis C virus (HCV) retrieved from the protein data bank (PDB)
      demonstrate that the proposed encoding scheme could precisely capture
      conformational patterns within HCV protein sequence. This promising result could
      provide some useful insights into the nature of HCV protein fold mechanism.

PMID- 17499552
TI  - Risk management in IVF.
AB  - Patient safety incidents occur in approximately 10% of hospital admissions in the
      UK. Although robust data are not available, assisted conception is unlikely to be
      any less prone to adverse incidents; indeed there have been several high-profile
      cases which have drawn attention to this problem. Recently established national
      reporting systems for adverse events are collecting data which will inform trends
      in patient safety. Because of the nature of the work undertaken in assisted
      conception, there is the potential to affect not only future generations but also
      many patients simultaneously because of storage of biological material. It is
      therefore important to implement strategies to reduce the likelihood of patient
      safety incidents. Established methodologies exist for the reactive (root cause
      analysis) and the proactive assessment of risk (failure mode effects analysis).
      Furthermore, establishing the detail of a process and its context through process
      mapping is an important prerequisite for understanding its risk. The knowledge
      gained through these enquiries enables the implementation of an effective risk
      management programme which this chapter examines in detail.

PMID- 17499553
TI  - Current treatment options for abnormal uterine bleeding: an evidence-based
      approach.
AB  - Heavy menstrual bleeding is the predominant complaint in women with abnormal
      uterine bleeding. Treatment options are drug therapy, and first- and second
      generation endometrial resection. Many women will subsequently have a
      hysterectomy. Uterine fibroids are the most common solid pelvic tumours in women,
      and although many fibroids seem to cause no symptoms, they can have serious
      adverse effects and impact on quality of life. As women postpone having children,
      gynaecologists will have to manage fibroids and polyps in a conservative manner.
      The past decade has witnessed the development of highly sophisticated diagnostic
      and therapeutic technology for women suffering from menorrhagia, fibroids and
      polyps, including minimally invasive uterine therapy. The tools currently at our
      disposal permit greater management flexibility, which must be tailored to the
      individual clinical situation. This chapter reviews the evidence-based approach
      and minimally invasive therapy.

PMID- 17499554
TI  - Evaluation of sleep habits in children with epilepsy.
AB  - Sleep disturbances are a common complaint among patients with epilepsy. Studies
      assessing the relationship between sleep and epilepsy during childhood are
      scarce. The purpose of this study was to evaluate sleep habits in children with
      epilepsy. This cross-sectional study of children with and without epilepsy
      employed two questionnaires to evaluate sleep habits. Characteristics of both
      sleep habits and epilepsy (type of seizure, epileptic syndrome, number of
      seizures, use of anticonvulsant drugs) were collected from parental interviews
      and medical records. Our results indicate that children with epilepsy have a
      greater incidence of sleep problems compared with children without epilepsy. In
      those with epilepsy, we observed that nocturnal seizures, polytherapy,
      developmental delay, refractory epilepsy, generalized seizures, and epileptic
      syndromes with an unfavorable outcome are associated with poor sleep habits.

PMID- 17499555
TI  - Substance use disorders in a primary care sample receiving daily opioid therapy.
AB  - The primary goal of this paper was to present a comprehensive picture of
      substance use disorders in a sample of patients receiving opioid therapy from
      their primary care physician. A second goal was to determine the relation of
      positive urine screens and aberrant drug behaviors to opioid use disorders. The
      study recruited 801 adults receiving daily opioid therapy from the primary care
      practices of 235 family physicians and internists in 6 health care systems in
      Wisconsin. The 6 most common pain diagnoses were degenerative arthritis, low back
      pain, migraine headaches, neuropathy, and fibromyalgia. The point prevalence of
      current (DSM-IV criteria in the past 30 days) substance abuse and/or dependence
      was 9.7% (n=78) and 3.8% (30) for an opioid use disorder. A logistic regression
      model found that current substance use disorders were associated with age between
      18 and 30 (OR=6.17: 1.99 to 19.12), severity of lifetime psychiatric disorders
      (OR=6.17; 1.99 to 19.12), a positive toxicology test for cocaine (OR=5.92; 2.60
      to 13.50) or marijuana (OR=3.52; 1.85 to 6.73), and 4 aberrant drug behaviors
      (OR=11.48; 6.13 to 21.48). The final model for opioid use disorders was limited
      to aberrant behaviors (OR=48.27; 13.63 to 171.04) as the other variables dropped
      out of the model. PERSPECTIVE: This study found that the frequency of opioid use
      disorders was 4 times higher in patients receiving opioid therapy compared with
      general population samples (3.8% vs 0.9%). The study also provides quantitative
      data linking aberrant drug behaviors to opioid use disorders.

PMID- 17499556
TI  - Antimicrobial properties of two purified skin peptides from the mink frog (Rana
      septentrionalis) against bacteria isolated from the natural habitat.
AB  - Numerous peptides exhibiting antimicrobial properties have been isolated from the
      skins of many amphibian species. These peptides offer an innate chemical defense
      system against various microbial agents that exist in the amphibian's
      environment. Amphibian skin peptides are typically tested for antimicrobial
      activity against microbial strains that are pathogenic to humans, but not on
      potential pathogenic or opportunistic bacteria that exist in the organism's
      habitat. Two peptides, a brevinin-2-related peptide and temporin-1SPb previously
      isolated from secretions of the mink frog, Rana septentrionalis, were tested for
      antimicrobial activity on bacterial isolates endemic to the frog's habitat. Ten
      isolates were identified, using 16S rRNA gene sequencing techniques, in the
      genera Pseudomonas, Serratia, Bacillus, Aeromonas, Burkholderia, Microbacterium,
      and Delftia. Bacterial isolates were tested with peptides at concentrations
      ranging from 0.8 microM to 1000 microM to determine the minimum inhibitory
      concentration (MIC) to inhibit growth. Growth of four of the isolates was
      inhibited by temporin-1SPb at the concentrations used, but all of the isolates
      were inhibited by the brevinin-2-related within the range of peptide
      concentrations used. This demonstrates the efficacy of both peptides as a
      component of the frog's innate chemical defense system.

PMID- 17499557
TI  - Icariin enhances endothelial nitric-oxide synthase expression on human
      endothelial cells in vitro.
AB  - Icariin, a flavonoid isolated from Epimedii herba, is considered to be the major
      therapeutical constituent of E. herba. The aim of this study was to investigate
      the possible protective effects and to clarify the mechanism of icariin on
      endothelial cells in vitro. Incubation of human umbilical vein endothelial cells
      (HUVEC) derived EA. hy926 cells with icariin(0.1, 1, 10 micromol l(-1)) from 6 h
      to 72 h, then the production of NO was measured to evaluate the protective
      effects of icariin. RT-PCR was employed to confirm the mRNA expression of
      endothelial nitric oxide synthase (eNOS). Western blotting was used to evaluate
      the protein expression of eNOS. NO production was enhanced in a time- and
      concentration-dependent manner (P<0.05), which was well matched with the
      expression of eNOS mRNA (up to 2.4-fold) and protein (up to 2.5-fold) after long
      term incubation with icariin in endothelial cells (P<0.05). Moreover, activated
      NF-kappaB was increased in EA. hy926 cells incubated with icariin for 24 h, in
      association with an increase in the expression of eNOS gene. In addition to its
      long-term effects on eNOS expression, icariin also enhanced the production of
      bioactive NO in the short-term (after a 5 min incubation, P<0.05). In concert
      with other effects, the protective effects of icariin on endothelial cells may
      contribute to the cardiovascular protective effects.

PMID- 17499558
TI  - Direct electrochemistry and bioelectrocatalysis of hemoglobin immobilized on
      carbon black.
AB  - It is reported for the first time that hemoglobin (Hb) was immobilized on the
      surface of carbon black powders modified at the surface of a glassy carbon
      electrode. The cyclic voltammetric results showed that the immobilized Hb could
      undergo a direct quasi-reversible electrochemical reaction. Its formal potential,
      E(0), is -0.330 V in phosphate buffer solution (pH 6.9) at a scan rate of 100
      mV/s and is almost independent of the scan rate in the range of 40-200 mV/s. The
      dependence of E(0), on the pH of the buffer solution indicated that the
      conversion of Hb-Fe(III)/Hb-Fe(II) is a one-electron-transfer reaction process
      coupled with one-proton-transfer. The experimental results also demonstrated that
      the immobilized Hb retained its bioelectrocatalytic activity for the reduction of
      H(2)O(2). Furthermore, the immobilized Hb can be stored at 4 degrees C for
      several weeks without any loss of the enzyme activity. Thus, the immobilized Hb
      may be used as a biocathodic catalyst in biofuel cells.

PMID- 17499559
TI  - Electrochemical insights into the ethanol tolerance of Saccharomyces cerevisiae.
AB  - It is expected that intracellular redox activity may closely related to catabolic
      states of living cells, based on which a mediated electrochemical method has been
      proposed to measure the ethanol tolerance of the yeast Saccharomyces cerevisiae
      AS 3800. The couple menadione/ferricyanide was employed as a carrier mediator
      system, sensing intracellular redox activity. Microelectrode voltammetric method
      was introduced to assay the ferrocyanide accumulations arising from menadione
      mediated reduction of ferricyanide by the yeast. The mediated electrochemical
      study show that the maximal ethanol tolerance limit of S. cerevisiae is about 25%
      (v/v) ethanol, which is consistent with the result obtained by the conventional
      fermentative ability measurement. Moreover, the electrochemical method for the
      first time confirmed that the specific activities of the glycolytic and
      alcohologenic enzymes within intact living cells remained high by the presence of
      sublethal ethanol, which was only predicted by in vitro enzymatic assay and
      cannot be measured by conventional method. The new method can be used as an easy
      and rapid method to determine the maximal ethanol tolerance of yeast cells.

PMID- 17499560
TI  - O6-methylguanine-DNA-methyltransferase (MGMT) gene therapy targeting
      haematopoietic stem cells: studies addressing safety issues.
AB  - As haematopoietic stem cell gene therapy utilizing O(6)-methylguanine-DNA
      methyltransferase has reached the clinical stage, safety-related questions become
      increasingly important. These issues concern insertional mutagenesis of viral
      vectors, the acute toxicity of pre-transplant conditioning protocols and in vivo
      selection regimens as well as potential genotoxic side effects of the alkylating
      drugs administered in this context. To address these questions, we have
      investigated toxicity-reduced conditioning regimens combining low-dose alkylator
      application with sublethal irradiation and have analysed their influence on
      engraftment and subsequent selectability of transduced haematopoietic stem cells.
      In addition, a strategy to monitor the acute and long-term genotoxic effects of
      drugs with high guanine-O(6) alkylating potential, such as
      chloroethylnitrosoureas or temozolomide is introduced. For this purpose, assays
      were implemented which allow an assessment of the generation and fate of primary
      drug-induced adducts as well as their long-term effect on chromosomal integrity
      at the single cell level.

PMID- 17499561
TI  - Cross talk of respiratory muscles It is possible to distinguish different muscle
      activity?

PMID- 17499562
TI  - Interstitial matrix and transendothelial fluxes in normal lung.
AB  - Pulmonary gas exchange critically depends upon the hydration state and the
      thinness of the interstitial tissue layer within the alveolo-capillary barrier.
      In the interstitium, fluid freely moving within the fibrous extracellular matrix
      equilibrates with water chemically interacting with hyaluronic acid and
      proteoglycans, the non-fibrillar components of the matrix. The integrity of the
      macromolecular assembly of the tissue matrix is required in all processes
      involved in establishing and maintaining the adequate interstitial tissue fluid
      volume, by providing: (a) a stiff three dimensional fibrous scaffold, functioning
      as an efficient safety factor to oppose fluid filtration into the tissue and
      preventing tissue fluid accumulation; (b) a restrictive perivascular and
      interstitial sieve with respect to plasma proteins; (c) a mechanical support to
      initial lymphatics. Therefore, disturbances of the deposition and/or turnover of
      the matrix and/or of its three dimensional architecture and composition are
      invariably accompanied by profound changes of the steady state tissue fluid
      dynamics, eventually evolving towards severe lung disease.

PMID- 17499563
TI  - Determination of oxalyl-coenzyme A decarboxylase activity in Oxalobacter
      formigenes and Lactobacillus acidophilus by capillary electrophoresis.
AB  - Oxalyl-coenzyme A decarboxylase (OXC) is a key enzyme in the catabolism of the
      highly toxic oxalate, catalysing the decarboxylation of oxalyl-coenzyme A (Ox
      CoA) to formyl-coenzyme A (For-CoA). In the present study, a capillary
      electrophoretic (CE) method was proposed for the assessment of the activity of
      recombinant OXC from two bacteria, namely Oxalobacter formigenes DSM 4420 and
      Lactobacillus acidophilus LA 14. In particular, the degradation of the substrate
      Ox-CoA occurring in the enzymatic reaction could be monitored by the off-line CE
      method. A capillary permanently coated with polyethylenimine (PEI) was used and
      in the presence of a neutral background electrolyte (50 mM phosphate buffer at pH
      7.0), a reversal of the electroosmotic flow was obtained. Under these conditions,
      the anodic migration of Ox-CoA (substrate) and For-CoA (reaction product)
      occurred and their separation was accomplished in less than 12 min. The CE method
      was validated for selectivity, linearity (range of Ox-CoA within 0.005-0.650 mM),
      sensitivity (LOD of 1.5 microM at the detection wavelength of 254 nm), precision
      and accuracy. Steady state kinetic constants (V(max), K(m) or k') of OXC were
      finally estimated for both the bacteria showing that although L. acidophilus LA
      14 provided a lower oxalate breakdown than O. formigenes DSM 4420, it could be a
      potentially useful probiotic in the prevention of diseases related to oxalate.

PMID- 17499564
TI  - Development of a SPE/HPLC/DAD method for the determination of antileishmanial 2
      substituted quinolines and metabolites in rat plasma.
AB  - A SPE/HPLC/DAD method was developed for the in vivo monitoring of three new
      antileishmanial 2-substituted quinolines under study in our laboratory for the
      development of an oral treatment. Three phase I metabolites were included in this
      work for the optimization of the method. Trifunctional tC(18) cartridges
      (resulting from the reaction of trifunctional silanes with silica surface) were
      selected among four sorbents tested. Two linear gradients were developed to
      ensure resolution of metabolites. Recovery of quinolines from rat plasma was
      comprised between 80.6 and 88.2%. In a drug development perspective, apparent
      pK(a), lipophilicity and solubility were determined, as well as the extent of
      plasma protein or albumin binding.

PMID- 17499565
TI  - Relevance of a combined UV and single mass spectrometry detection for the
      determination of tenofovir in human plasma by HPLC in therapeutic drug
      monitoring.
AB  - A sensitive high-performance liquid chromatography method coupled to UV and
      single mass spectrometry (MS) detection was developed for the determination of
      tenofovir in human plasma. A solid phase extraction procedure (Bond-Elut C18
      Varian cartridges) provided high extraction efficiency (91% for tenofovir and
      68.8% for the internal standard, 3-methylcytidine). An atlantis-dC-18 analytical
      column is used with an isocratic mode elution of a mixture (pH 2.5) of ammonium
      acetate/methanol (98.5:1.5, v/v). Detection was performed at 260 nm and by using
      the ion at m/z 288. The signals from both detectors were validated over the range
      of 10-1000 ng mL(-1) and were found to be linear, accurate and precise. At the
      lowest limit of quantification, 10 ng mL(-1) for UV and 5 ng mL(-1) for MS, the
      average coefficient of variation was 6.9 and 3.9%, respectively. To investigate
      the potential of the validated method for clinical studies, more than 170 samples
      from HIV-infected adult patients were then analyzed with this assay. A good
      correlation was observed between the results obtained with both detectors.
      However, in several cases discordant results were observed between UV and MS
      detections. Therefore, tenofovir can sometimes suffer from interferences using
      either UV or single MS detection. We concluded that the double detection allows
      to obtain a more specific quantification of tenofovir. The present assay is sound
      and can be used for therapeutic drug monitoring allowing a higher reliability of
      the results which are transmitted to the medical team.

PMID- 17499566
TI  - Two-step purification of a highly thermostable alkaline protease from salt
      tolerant alkaliphilic Streptomyces clavuligerus strain Mit-1.
AB  - An alkaline protease from a salt-tolerant alkaliphilic Streptomyces clavuligerus
      was purified to homogeneity by 141-fold with a yield of 12% using two-step method
      of salt precipitation and ion exchange chromatography on DEAE cellulose. The
      apparent molecular mass was 49+/-2 kDa and the enzyme appeared as monomer based
      on SDS and Native-PAGE. The temperature optimum was 70 degrees C with significant
      stability at 60-80 degrees C for more than 60 min. The enzyme was active over the
      pH range of 8.5-11, with an optimum at 10-11. The serine nature of the protease
      was confirmed by PMSF inhibition. The enzyme was highly resistant against
      chemical denaturation and displayed varied effects towards metal ions. The
      results are significant as extremozymes are difficult to purify and therefore, a
      two-step purification of alkaline protease from relatively less explored group of
      actinomycetes is quite appealing.

PMID- 17499567
TI  - Prosthetic mesh for infected abdominal wall defects? Report of a patient with a
      large full thickness abdominal wall defect and colostomy due to a gunshot wound.
AB  - Reconstruction of large, infected abdominal wall defects is often difficult.
      Local factors, such as defect size, presence of infection, adequate skin coverage
      and presence of enteric fistulae dictate the reconstructive method that can be
      used. Placement of prosthetic mesh materials into infected defects was generally
      not recommended due to a high rate of extrusion and fistulae. We present a
      patient with a large infected abdominal wall defect, exposed intestines and
      colostomy due to a gunshot wound that was successfully treated with a
      polypropylene mesh reinforcement and free latissimus dorsi muscle flap coverage.
      Twelve months following abdominal wall reconstruction with stable soft tissue
      cover, the patient is without any signs of hernia or infection. We conclude that
      prosthetic mesh repair of infected abdominal wall defects of such characteristics
      that preclude other reconstructive procedures can be attempted provided there is
      coverage with a well vascularised tissue.

PMID- 17499568
TI  - The 'propeller' distal anteromedial thigh perforator flap. Anatomic study and
      clinical applications.
AB  - BACKGROUND: The leg and peripatellar region have always been known as a poor
      source of available flaps. One flap donor site that has proven to be adequate is
      the distal anteromedial half of the thigh. Due to the potential and plentiful
      vascular sources of this anatomic region we decided to study the distal
      anteromedial thigh and its clinical applications. ANATOMIC STUDY: Sixteen
      cryopreserved inferior limbs were latex-injected in the femoral artery and the
      skin perforators of the distal anteromedial thigh and their source vessels were
      studied. CLINICAL STUDY: In a period between December 2000 and June 2005, skin
      islands from the distal anteromedial aspect of the thigh of six patients were
      transferred, as local perforator flaps, to reconstruct the peripatellar region
      and upper leg soft tissue defects. Every flap was based on a single adequate
      perforator vessel. The tissue was rotated, as a 'propeller', through 180 degrees
      and the flap was named 'the propeller distal anteromedial thigh perforator flap'.
      RESULTS: In the distal anteromedial thigh the anatomic variability includes not
      only perforator vessels but also their source vessels. Skin perforators can come
      from each of the deep vessels. Our clinical results, with a follow up of 1-4
      years, show no total flap losses. Partial necrosis > 20% happened in one diabetic
      patient. CONCLUSION: The propeller distal anteromedial thigh perforator flap can
      be reliably transferred based on only one adequate perforator vessel. It reduces
      the morbidity and improves the availability of the distal anteromedial thigh as a
      flap donor site and represents an additional reconstructive option for knee and
      upper leg defects.

PMID- 17499569
TI  - Peripartum urinary incontinence: a study of midwives' knowledge and practices.
AB  - Urinary incontinence impacts on women's quality of life and their wellbeing. The
      objectives of this study were to obtain knowledge and information on midwives'
      assessment and management practices of urinary incontinence in childbearing women
      and to explore midwives' knowledge of risk factors associated with developing
      urinary incontinence. A non-experimental descriptive research design was used,
      and participants were current members of the Victorian branch of the Australian
      College of Midwives. Data was obtained using a survey tool that contained both
      qualitative and quantitative questions. Key findings indicated that the majority
      of midwives do not assess women for urinary incontinence during the peripartum
      period and guidelines for bladder management in maternity services were lacking.

PMID- 17499571
TI  - A nonisotopic assay for unambiguous assignment of DNA glycosylase functionality.

PMID- 17499570
TI  - Is short vertebral height always an osteoporotic fracture? The Osteoporosis and
      Ultrasound Study (OPUS).
AB  - INTRODUCTION AND HYPOTHESIS: Diagnosis of prevalent osteoporotic vertebral
      fracture is complicated by normal or developmental variation in vertebral shape
      or size and non-osteoporotic deformities that appear to have 'reduced' height.
      Using our visual approach, the algorithm-based qualitative method (ABQ) a
      vertebra with apparent "reduced" height without evidence of osteoporotic endplate
      depression is classified as non-osteoporotic short vertebral height (SVH). We
      aimed to determine whether ABQ classification of SVH represents true or false
      negative diagnosis of osteoporotic vertebral fracture, by testing the
      associations with clinical outcomes of osteoporosis or vertebral fracture.
      METHODS: The ABQ method was used to assess spinal radiographs acquired at
      baseline for a subset of 904 postmenopausal women participating in the
      Osteoporosis and Ultrasound Study (OPUS). The sample was enriched with vertebral
      fracture cases. Subjects were categorized by ABQ diagnosis as (i) normal, (ii)
      non-osteoporotic short vertebral height (SVH) or (iii) osteoporotic vertebral
      fracture. RESULTS: Women were classified by ABQ as follows: osteoporotic
      vertebral fracture, n=231; SVH, n=376 and normal, n=297. Women with vertebral
      fracture were older, with lower height, weight and height loss than those
      classified as SVH or normal. Women with SVH were heavier and older, with greater
      historical height loss than normal women. Age-adjusted SD units (z-scores) for
      BMD were lower than expected among women with osteoporotic vertebral fracture,
      but not among those with SVH. There was a significant association between
      diagnosis of osteoporotic vertebral fracture and history of low-trauma non
      vertebral and vertebral fracture (p<0.001, odds ratios=3.2 and 20.6,
      respectively). There was also an association between diagnosis of SVH and
      previous low-trauma non-vertebral fracture (p<0.05, odds ratio=1.7). CONCLUSIONS:
      Short vertebral height without evidence of central endplate fracture in
      postmenopausal women is largely unrelated to osteoporosis. Quantitative
      morphometry should not be used alone for the assessment of vertebral fracture in
      clinical decision making: we recommend differential diagnosis of morphometric
      vertebral deformities by an expert reader to rule out non-osteoporotic
      deformities with short vertebral height.

PMID- 17499572
TI  - [The Prader-Willi syndrome].
AB  - Prader-Willi syndrome is a rare genetic disorder, affecting 1 out of 25,000
      births, in which a critical region of chromosome 15, the 15q11-q13 region, is
      affected. At birth, PWS infants exhibit severe hypotonia that partially improves,
      explaining in part suckling and swallowing troubles and the delay in psychomotor
      development. Characteristic facial features (dysmorphic syndrome) and very small
      hands and feet are frequently observed at this age. After this initial phase, the
      most striking signs appear: hyperphagia and absence of satiety often leading to
      severe obesity in affected children as young as two years. The situation may
      deteriorate quickly without adequate outside controls and explains in great part
      the morbidity and mortality of these patients. Other endocrine abnormalities in
      association with the hypothalamic-pituitary abnormalities contribute to the
      clinical picture of short stature due to a growth hormone deficiency and
      incomplete pubertal development. The degree of cognitive dysfunction varies
      widely from one child to another. It is associated with learning disabilities and
      impaired speech and language development worsened by psychological and
      behavioural troubles. The expert consensus is that diagnosis should be based on
      clinical criteria (Holm's criteria of 1993, revised in 2001) with confirmation by
      genetic study. Most cases are sporadic and familial cases are rare, those
      informations should be given as genetic counselling. It is necessary to set up a
      global and multidisciplinary management. Early diagnosis, early multidisciplinary
      care and growth hormone treatment have greatly improved the quality of life of
      these children. We have no long-term data on the effect of GH treatment in
      adults, on behavioural troubles and autonomy of the persons. In adults,
      complications particularly linked to obesity and problems of autonomy are still
      very important.

PMID- 17499573
TI  - Flightdeck and air traffic control collaboration evaluation (FACE): evaluating
      aviation communication in the laboratory and field.
AB  - The challenge to anticipate the human factors impact of introducing new
      technologies into a safety critical environment can be addressed in a number of
      ways. This paper presents a research programme that utilised both laboratory- and
      field-based assessments to examine the way in which datalink and freeflight may
      affect the communication and collaboration between pilots, air traffic
      controllers, and other actors and artefacts in the flightdeck-air traffic control
      (ATC) joint cognitive system. An overview of the results from these studies is
      presented, and guidance is provided as to the likely situations in which this new
      technology is most likely to be successfully applied. In addition, the
      methodological approach of combining results from field and laboratory data is
      discussed.

PMID- 17499574
TI  - Kinetic and biochemical characterization of an ecto-nucleotide
      pyrophosphatase/phosphodiesterase (EC 3.1.4.1) in cells cultured from
      submandibular salivary glands of rats.
AB  - The participation of ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP)
      activity in the nucleotide hydrolysis by salivary gland cells of rats was
      evaluated using p-nitrophenyl 5'-thymidine monophosphate (p-Nph-5'-TMP) as a
      substrate for this enzyme. We investigated the biochemical characteristics of
      this ectoenzyme in cells cultured from submandibular salivary glands of rats.
      Primary cell cultures demonstrated ecto-nucleotide
      pyrophosphatase/phosphodiesterase (E-NPP) activities, which could be observed by
      extracellular hydrolysis of p-Nph-5'-TMP and other biochemical characteristics
      such as dependence of metal ions, dependence of pH alkaline and inactivation by a
      metal ion chelator. The Km value for the hydrolysis of p-Nph-5'-TMP was 280.7+/
      34.2 microM (mean+/-S.D., n=4) and Vmax was 721.31+/-225nmol p-nitrophenol/min/mg
      (mean+/-S.D., n=4). We suggest that E-NPP is co-localized with an ecto-ATP
      diphosphohydrolase/ecto-NTPDase and an ecto-5'-nucleotidase, since these enzymes
      probably act under different conditions. It may be postulated that the
      physiological role for these ecto-enzymes is to terminate the action of the co
      transmitter ATP, generating adenosine.

PMID- 17499575
TI  - The mitochondrial ryanodine receptor in rat heart: a pharmaco-kinetic profile.
AB  - A protein discovered within inner mitochondrial membranes (IMM), designated as
      the mitochondrial ryanodine receptor (mRyR), has been recognized recently as a
      modulator of Ca(2+) fluxes in mitochondria. The present study provides
      fundamental pharmacological and electrophysiological properties of this mRyR. Rat
      cardiac IMM fused to lipid bilayers revealed the presence of a mitochondrial
      channel with gating characteristics similar to those of classical sarcoplasmic
      reticulum RyR (SR-RyR), but a variety of other mitochondrial channels obstructed
      clean recordings. Mitochondrial vesicles were thus solubilized and subjected to
      sucrose sedimentation to obtain mRyR-enriched fractions. Reconstitution of
      sucrose-purified fractions into lipid bilayers yielded Cs(+)-conducting, Ca(2+)
      sensitive, large conductance (500-800 pS) channels with signature properties of
      SR-RyRs. Cytosolic Ca(2+) increased the bursting frequency and mean open time of
      the channel. Micromolar concentrations of ryanodine induced the appearance of
      subconductance states or inhibited channel activity altogether, while Imperatoxin
      A (IpTx(a)), a specific activator of RyRs, reversibly induced the appearance of
      distinct subconductance states. Remarkably, the cardiac mRyR displayed a Ca(2+)
      dependence of [(3)H]ryanodine binding curve similar to skeletal RyR (RyR1), not
      cardiac RyR (RyR2). Overall, the mRyR displayed elemental attributes that are
      present in single channel lipid bilayer recordings of SR-RyRs, although some
      exquisite differences were also noted. These results therefore provide the first
      direct evidence that a unique RyR occurs in mitochondrial membranes.

PMID- 17499576
TI  - Phosphatidylcholine and sphingomyelin containing an elaidoyl fatty acid can form
      cholesterol-rich lateral domains in bilayer membranes.
AB  - Elaidic acid is a trans-fatty acid found in many food products and implicated for
      having potentially health hazardous effects in humans. Elaidic acid is readily
      incorporated into membrane lipids in vivo and therefore affects processes
      regulating membrane physical properties. In this study the membrane properties of
      sphingomyelin and phosphatidylcholine containing elaidic acid (N-E-SM and PEPC)
      were determined in bilayer membranes with special emphasis on their interaction
      with cholesterol and participation in ordered domain formation. In agreement with
      previous studies the melting temperatures were found to be about 20 degrees C
      lower for the elaidoyl than for the corresponding saturated lipids. The trans
      unsaturation increased the polarity at the membrane-water interface as reported
      by Laurdan fluorescence. Fluorescence quenching experiments using cholestatrienol
      as a probe showed that both N-E-SM and PEPC were incorporated in lateral membrane
      domains with sterol and saturated lipids. At low temperatures the elaidoyl lipids
      were even able to form sterol-rich domains without any saturated lipids present
      in the bilayer. We conclude from this study that the ability of N-E-SM and PEPC
      to form ordered domains together with cholesterol and saturated phospho- and
      sphingolipids in model membranes indicates that they might have an influence on
      raft formation in biological membranes.

PMID- 17499577
TI  - Peptide degradation is a critical determinant for cell-penetrating peptide
      uptake.
AB  - Cell-penetrating peptide mediated uptake of labels appears to follow an
      equilibrium-like process. However, this assumption is only valid if the peptides
      are stabile. Hence, in this study we investigate intracellular and extracellular
      peptide degradation kinetics of two fluorescein labeled cell-penetrating
      peptides, namely MAP and penetratin, in Chinese hamster ovarian cells. The
      degradation and uptake kinetics were assessed by RP-HPLC equipped with a
      fluorescence detector. We show that MAP and penetratin are rapidly degraded both
      extracellularly and intracellularly giving rise to several degradation products.
      Kinetics indicates that intracellularly, the peptides exist in (at least) two
      distinct pools: one that is immediately degraded and one that is stabile.
      Moreover, the degradation could be decreased by treating the peptides with BSA
      and phenanthroline and the uptake was significantly reduced by cytochalasin B,
      chloroquine and energy depletion. The results indicate that the extracellular
      degradation determines the intracellular peptide concentration in this system and
      therefore the stability of cell-penetrating peptides needs to be evaluated.

PMID- 17499578
TI  - Food safety reform in the USA.

PMID- 17499579
TI  - Protecting the health of men who have sex with men.

PMID- 17499580
TI  - Improving end-of-life care for children.

PMID- 17499581
TI  - Can aspirin prevent colorectal cancer?

PMID- 17499582
TI  - Preventing necrotising enterocolitis with probiotics.

PMID- 17499583
TI  - Summing the risk of NSAID therapy.

PMID- 17499584
TI  - Hepatitis B in China.

PMID- 17499585
TI  - Can the US congress slow down and get FDA reform right?

PMID- 17499586
TI  - Greenhouse-gas costs of clinical trials.

PMID- 17499587
TI  - Clinical update: irritable bowel syndrome.

PMID- 17499588
TI  - Francis Ka Leung Chan: advancing clinical research in Hong Kong.

PMID- 17499589
TI  - Male circumcision in HIV prevention.

PMID- 17499590
TI  - Male circumcision in HIV prevention.

PMID- 17499591
TI  - Male circumcision in HIV prevention.

PMID- 17499593
TI  - Male circumcision in HIV prevention.

PMID- 17499594
TI  - Exemestane or tamoxifen?

PMID- 17499595
TI  - Exemestane or tamoxifen?

PMID- 17499597
TI  - Exemestane or tamoxifen?

PMID- 17499598
TI  - Folate and ageing.

PMID- 17499600
TI  - Folate and ageing.

PMID- 17499601
TI  - Complementary therapies in juvenile idiopathic arthritis.

PMID- 17499602
TI  - Effect of aspirin on long-term risk of colorectal cancer: consistent evidence
      from randomised and observational studies.
AB  - BACKGROUND: Randomised trials have shown that aspirin reduces the short-term risk
      of recurrent colorectal adenomas in patients with a history of adenomas or
      cancer, but large trials have shown no effect in primary prevention of colorectal
      cancer during 10 years' follow-up. However, the delay from the early development
      of adenoma to presentation with cancer is at least 10 years. We aimed to assess
      the longer-term effect of aspirin on the incidence of cancers. METHODS: We
      studied the effect of aspirin in two large randomised trials with reliable post
      trial follow-up for more than 20 years: the British Doctors Aspirin Trial
      (N=5139, two-thirds allocated 500 mg aspirin for 5 years, a third to open
      control) and UK-TIA Aspirin Trial (N=2449, two-thirds allocated 300 mg or 1200 mg
      aspirin for 1-7 years, a third placebo control). We also did a systematic review
      of all relevant observational studies to establish whether associations were
      consistent with the results of the randomised trials and, if so, what could be
      concluded about the likely effects of dose and regularity of aspirin use, other
      non-steroidal anti-inflammatory drugs (NSAID), and the effect of patient
      characteristics. RESULTS: In the randomised trials, allocation to aspirin reduced
      the incidence of colorectal cancer (pooled HR 0.74, 95% CI 0.56-0.97, p=0.02
      overall; 0.63, 0.47-0.85, p=0.002 if allocated aspirin for 5 years or more).
      However, this effect was only seen after a latency of 10 years (years 0-9: 0.92,
      0.56-1.49, p=0.73; years 10-19: 0.60, 0.42-0.87, p=0.007), was dependent on
      duration of scheduled trial treatment and compliance, and was greatest 10-14
      years after randomisation in patients who had had scheduled trial treatment of 5
      years or more (0.37, 0.20-0.70, p=0.002; 0.26, 0.12-0.56, p=0.0002, if
      compliant). No significant effect on incidence of non-colorectal cancers was
      recorded (1.01, 0.88-1.16, p=0.87). In 19 case-control studies (20 815 cases) and
      11 cohort studies (1 136 110 individuals), regular use of aspirin or NSAID was
      consistently associated with a reduced risk of colorectal cancer, especially
      after use for 10 years or more, with no difference between aspirin and other
      NSAIDs, or in relation to age, sex, race, or family history, site or
      aggressiveness of cancer, or any reduction in apparent effect with use for 20
      years or more. However, a consistent association was only seen with use of 300 mg
      or more of aspirin a day, with diminished and inconsistent results for lower or
      less frequent doses. INTERPRETATION: Use of 300 mg or more of aspirin a day for
      about 5 years is effective in primary prevention of colorectal cancer in
      randomised controlled trials, with a latency of about 10 years, which is
      consistent with findings from observational studies. Long-term follow-up is
      required from other randomised trials to establish the effects of lower or less
      frequent doses of aspirin.

PMID- 17499603
TI  - Probiotics for prevention of necrotising enterocolitis in preterm neonates with
      very low birthweight: a systematic review of randomised controlled trials.
AB  - BACKGROUND: Results of recent clinical trials suggest that probiotic
      supplementation reduces the risk of necrotising enterocolitis in preterm
      neonates. We aimed to systematically review randomised controlled trials
      evaluating efficacy and safety of any probiotic supplementation (started within
      first 10 days, duration > or =7 days) in preventing stage 2 or greater
      necrotising enterocolitis in preterm neonates (gestation <33 weeks) with very low
      birthweight (<1500 g). METHODS: We followed the standard search strategy of the
      Cochrane Neonatal Review Group. We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL), Medline, Embase, CINAHL databases, and proceedings
      of the Pediatric Academic Society meetings (from 1980) and Pediatric
      Gastroenterology conferences (from 1980) in November, 2006. RESULTS: Seven of 12
      randomised controlled trials retrieved (n=1393) were eligible for inclusion in
      the analysis. Meta-analysis using a fixed effects model estimated a lower risk of
      necrotising enterocolitis (relative risk 0.36, 95% CI 0.20-0.65) in the probiotic
      group than in controls. Risk of sepsis did not differ significantly between
      groups (0.94, 0.74-1.20). Risk of death was reduced in the probiotic group (0.47,
      0.30-0.73). The time to full feeds was significantly shorter in the probiotic
      group (weighted mean difference -2.74 days, 95% CI -4.98 to -0.51) than in
      controls. CONCLUSION: Probiotics might reduce the risk of necrotising
      enterocolitis in preterm neonates with less than 33 weeks' gestation. However,
      the short-term and long-term safety of probiotics needs to be assessed in large
      trials. Unanswered questions include the dose, duration, and type of probiotic
      agents (species, strain, single or combined, live or killed) used for
      supplementation.

PMID- 17499604
TI  - Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for
      prevention of recurrent ulcer bleeding in patients at very high risk: a double
      blind, randomised trial.
AB  - BACKGROUND: Guidelines on pain management recommend that patients at risk of
      ulcers receive either a cyclo-oxygenase (COX 2) inhibitor or a non-steroidal anti
      inflammatory drug (NSAID) with a proton-pump inhibitor (PPI). These two
      treatments have similar effectiveness, but they are insufficient for protection
      of patients at very high risk for ulcer bleeding. We aimed to test the hypothesis
      that in patients with previous ulcer bleeding induced by non-selective NSAIDs,
      combined treatment with the COX 2 inhibitor celecoxib and the PPI esomeprazole
      would be better than celecoxib alone for prevention of recurrent ulcer bleeding.
      METHODS: 441 consecutively presenting patients who were taking non-selective
      NSAIDs for arthritis were recruited to our single-centre, prospective,
      randomised, double-blind trial after admission to hospital with upper
      gastrointestinal bleeding. Patients were enrolled after their ulcers had healed
      and a histological test for Helicobacter pylori was negative. All patients were
      given 200 mg celecoxib twice daily. 137 patients were randomly assigned to
      receive 20 mg esomeprazole twice daily (combined-treatment group), and 136 to
      receive a placebo (control group) for 12 months. The primary endpoint was
      recurrent ulcer bleeding during treatment or within 1 month of the end of
      treatment. Analysis was by intention to treat. This trial is registered with
      ClinicalTrials.gov, number NCT00365313. FINDINGS: Combination treatment was more
      effective than celecoxib alone for prevention of ulcer bleeding in patients at
      high risk. The 13-month cumulative incidence of the primary endpoint was 0% in
      the combined-treatment group and 12 (8.9%) in the controls (95% CI difference,
      4.1 to 13.7; p=0.0004). The median follow-up was 13 months (range 0.4-13.0).
      Discontinuation of treatment and the incidence of adverse events were similar in
      the two treatment groups. INTERPRETATION: Patients at very high risk for
      recurrent ulcer bleeding who need anti-inflammatory analgesics should receive
      combination treatment with a COX 2 inhibitor and a PPI. Our findings should
      encourage guideline committees to review their recommendations for patients at
      very high risk of recurrent ulcer bleeding.

PMID- 17499605
TI  - Inflammatory bowel disease: cause and immunobiology.
AB  - Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel
      disorders. In this paper, we discuss how environmental factors (eg, geography,
      cigarette smoking, sanitation and hygiene), infectious microbes, ethnic origin,
      genetic susceptibility, and a dysregulated immune system can result in mucosal
      inflammation. After describing the symbiotic interaction of the commensal
      microbiota with the host, oral tolerance, epithelial barrier function, antigen
      recognition, and immunoregulation by the innate and adaptive immune system, we
      examine the initiating and perpetuating events of mucosal inflammation. We pay
      special attention to pattern-recognition receptors, such as toll-like receptors
      and nucleotide-binding-oligomerisation-domains (NOD), NOD-like receptors and
      their mutual interaction on epithelial cells and antigen-presenting cells. We
      also discuss the important role of dendritic cells in directing tolerance and
      immunity by modulation of subpopulations of effector T cells, regulatory T cells,
      Th17 cells, natural killer T cells, natural killer cells, and monocyte
      macrophages in mucosal inflammation. Implications for novel therapies, which are
      discussed in detail in the second paper in this Series, are covered briefly.

PMID- 17499606
TI  - Inflammatory bowel disease: clinical aspects and established and evolving
      therapies.
AB  - Crohn's disease and ulcerative colitis are two idiopathic inflammatory bowel
      disorders. In this paper we discuss the current diagnostic approach, their
      pathology, natural course, and common complications, the assessment of disease
      activity, extraintestinal manifestations, and medical and surgical management,
      and provide diagnostic and therapeutic algorithms. We critically review the
      evidence for established (5-aminosalicylic acid compounds, corticosteroids,
      immunomodulators, calcineurin inhibitors) and emerging novel therapies--including
      biological therapies--directed at cytokines (eg, infliximab, adalimumab,
      certolizumab pegol) and receptors (eg, visilizumab, abatacept) involved in T-cell
      activation, selective adhesion molecule blockers (eg, natalizumab, MLN-02,
      alicaforsen), anti-inflammatory cytokines (eg, interleukin 10), modulation of the
      intestinal flora (eg, antibiotics, prebiotics, probiotics), leucocyte apheresis
      and many more monoclonal antibodies, small molecules, recombinant growth factors,
      and MAP kinase inhibitors targeting various inflammatory cells and pathways.
      Finally, we summarise the practical aspects of standard therapies including
      dosing, precautions, and side-effects.

PMID- 17499607
TI  - Measuring health and disability.

PMID- 17499608
TI  - Profuse rectal bleeding of no visible cause.

PMID- 17499609
TI  - Neural differentiation of novel multipotent progenitor cells from cryopreserved
      human umbilical cord blood.
AB  - Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells, with
      practical and ethical advantages. To date, the presence of other stem cells in
      UCB remains to be established. We investigated whether other stem cells are
      present in cryopreserved UCB. Seeded mononuclear cells formed adherent colonized
      cells in optimized culture conditions. Over a 4- to 6-week culture period,
      colonized cells gradually developed into adherent mono-layer cells, which
      exhibited homogeneous fibroblast-like morphology and immunophenotypes, and were
      highly proliferative. Isolated cells were designated 'multipotent progenitor
      cells (MPCs)'. Under appropriate conditions for 2 weeks, MPCs differentiated into
      neural tissue-specific cell types, including neuron, astrocyte, and
      oligodendrocyte. Differentiated cells presented their respective markers,
      specifically, NF-L and NSE for neurons, GFAP for astrocytes, and
      myelin/oligodendrocyte for oligodendrocytes. In this study, we successfully
      isolated MPCs from cryopreserved UCB, which differentiated into the neural tissue
      specific cell types. These findings suggest that cryopreserved human UCB is a
      useful alternative source of neural progenitor cells, such as MPCs, for
      experimental and therapeutic applications.

PMID- 17499610
TI  - Anti-inflammatory effects of hydroxycinnamic acid derivatives.
AB  - NF-kappaB family of transcription factors are involved in numerous cellular
      processes, including differentiation, proliferation, and inflammation. It was
      reported that hydroxycinnamic acid derivatives (HADs) are inhibitors of NF-kappaB
      activation. Rice bran oil contains a lot of phytosteryl ferulates, one of HADs.
      We have investigated effects of phytosteryl ferulates on NF-kappaB activation in
      macrophage. Cycloartenyl ferulate (CAF), one of phytosteryl ferulates,
      significantly reduced lipopolysaccharide (LPS)-induced NO production and mRNA
      expression of inducible NO synthase and cyclooxygenese-2 but upregulated SOD
      activity. Electrophoresis mobility shift assay revealed that CAF inhibited DNA
      binding of NF-kappaB. CAF and phytosteryl ferulates probably have potentially
      anti-inflammatory properties.

PMID- 17499611
TI  - Notch ligand mRNA levels of human APCs predict Th1/Th2-promoting activities.
AB  - Although the contribution of Notch ligands expressed by antigen-presenting cells
      (APCs) to the Th1/Th2 differentiation has been suggested in mouse studies, their
      nature in humans remains obscure. To assess the issue, we examined correlation of
      Notch ligand mRNA levels of human APCs with Th1/Th2-promoting stimulations, i.e.
      Th1/Th2 adjuvant activities. The expression patterns of human dendritic cells
      (DCs) and leukemic cell line models of APCs differed partly from those previously
      observed in mouse DCs and by cellular types and maturation stages. Most
      strikingly, Th2 adjuvants enhanced the Delta1 expression on human APCs but did
      not induce Delta4 expression, which was induced by a Th1 adjuvant. The
      differential expression patterns suggest a distinct role of these Delta members
      in Th1/Th2 differentiation and their predictive potential for Th1/Th2-promoting
      activities.

PMID- 17499612
TI  - Taste-modifying sweet protein, neoculin, is received at human T1R3 amino terminal
      domain.
AB  - This study examines taste reception of neoculin, a Curculigo latifolia sweet
      protein with taste-modifying activity which converts sourness to sweetness.
      Neoculin tastes sweet to humans, but not to mice, and is received by the human
      sweet taste receptor hT1R2-hT1R3. In the present study with calcium imaging
      analysis of HEK cells expressing human and mouse T1Rs, we demonstrated that hT1R3
      is required for the reception of neoculin. Further experiments using human/mouse
      chimeric T1R3s revealed that the extracellular amino terminal domain (ATD) of
      hT1R3 is essential for the reception of neoculin. Although T1R2-T1R3 is known to
      have multiple potential ligand-binding sites to receive a wide variety of
      sweeteners, the present study is apparently the first to identify the ATD of
      hT1R3 as a new sweetener-binding region.

PMID- 17499613
TI  - Functional barrel cortex in 'hairless', nude mice.
AB  - Although nude mice are not truly hairless, they demonstrate abnormal hair
      structure and growth patterns, which are related to their genetic state. Whereas
      wild-type mice are born with visible vibrissae, nude mice are distinguishable at
      birth by the lack of visible vibrissae, which do not appear until approximately
      postnatal day 6. Additionally, adult nude mice have abnormal whisker cycling
      patterns in which structurally normal whisker follicles produce fragile whiskers
      which break or fallout leaving follicles whiskerless for several days before a
      fine replacement whisker appears and develops. The current study shows that
      despite these abnormal periods of whisker deprivation, the barrel cortex of nude
      mice develops a normal structural appearance viewed with cytochrome oxidase
      staining. Additionally, intrinsic optical imaging studies of barrel cortex
      responses to single whisker stimulation do not appear altered from normal despite
      periodic loss of adjacent whiskers.

PMID- 17499617
TI  - Communication: the key to the game.
AB  - Being a team physician requires a whole new set of communications skills,
      depending on the organization one is affiliated with. There may be a single
      expected procedure to follow, or multiple procedures may be required. Regardless,
      it is imperative for the team physician to understand that his or her role is
      vital to those who seek accurate and timely information, thus potentially
      requiring physicians to adapt their current methods for communicating. Learning
      how to communicate as a team physician in a timely and accurate manner,
      understanding the appropriate chain of command, and avoiding common pitfalls
      associated with improper and sometimes adverse forms of communication will pave
      the way for an excellent long-term working relationship.

PMID- 17499618
TI  - Accessibility of the team physician.
AB  - The transition to the care of the college student-athlete carries with it a
      number of adjustments. In private practice it is customary to make medical
      decisions and initiate therapies from the confines of the examination room. The
      doctor-patient relationship is the principal focus. Although this relationship
      remains paramount in college athletics, the world of concerned and affected
      parties dramatically expands. It is in this context that the authors explore the
      concept of access in the role of a team physician. To use what is becoming an
      over used cliche, what makes one a valued team physician is being "the right
      person, in the right place at the right time."

PMID- 17499619
TI  - Understanding the politics of being a team physician.
AB  - The team physician landscape is littered with political land mines. In the high
      stakes world of professional sports, the politics of each encounter and medical
      decision--from figuring out how to get hired, to setting up a communication chain
      of command, to treating visiting players, to fending off the media--must be
      identified, assessed, and resolved. Key information must be communicated
      according to the expectations and unique personalities of each owner, general
      manager, coach, trainer, and athlete. The best team physicians manage
      relationships, competing agendas, and politically charged circumstances as
      adeptly as they wield a scalpel.

PMID- 17499620
TI  - Building a sports medicine team.
AB  - There have been a growing number of participants in high school and collegiate
      athletics in recent years, placing ever-increasing demands on the sports medicine
      team. Building a winning sports medicine team is equally as important to the
      success of an athletic organization as fielding talented athletes. Acquisition of
      highly qualified, motivated, and hard-working individuals is essential in
      providing high quality and efficient health care to the athlete. Maintaining open
      paths of communication between all members of the team is the biggest key to
      success and an optimal way to avoid confusion and pitfalls.

PMID- 17499621
TI  - Establishing a new practice as a team physician.
AB  - The role of a team physician is an integral part of establishing a new practice.
      Regardless of the type of practice one enters, the team physician role provides
      an opportunity to establish an early referral base to build the foundation of a
      successful practice. Although this comes with great responsibility and
      significant time commitments, the joy of developing your practice doing what you
      enjoy most, sports medicine, makes these drawbacks less perceptible. Using all
      your potential resources and keeping your eye on the ball will simplify reaching
      the goal of having a happy, healthy, and rewarding career.

PMID- 17499622
TI  - Balancing life as a team physician.
AB  - This article reviews the author's ten commandments for a balanced life as a team
      physician: (1) Do the right thing, always, no exceptions; (2) It's better to be
      an advocate than curse your competition; (3) Don't demand respect from players
      and coaches, earn it; (4) Loyalty is the weakest of human values (5) Communicate:
      Team physicians must always be available to athletic training staff; (6) In order
      to hit the mark, one must aim a little higher; (7) Enjoy your role as team
      physician; (8) Remember the five A's--Availability, Ability, Affability,
      Advocacy, and Affiliation; (9) Dare to care; and (10) Don't forget your family
      and friends.

PMID- 17499623
TI  - Negotiating contractual relationships.
AB  - Team coverage can be the most rewarding and the most challenging aspect of a
      physician's career; however, evaluate the realistic risks and benefits of
      covering a team. Understand what the team is looking for. Prior physicians may
      have been dismissed for a specific action, may have left on their own, or may
      have been asked to pay for the privilege of serving. Tell the team what you have
      to offer and what you need to make the relationship work, and be prepared to walk
      away from the deal if the risks are too high. Understanding the implications of
      working without a contract and the elements of an appropriate contract is
      paramount to a successful relationship.

PMID- 17499624
TI  - Understanding organization structures of the college, university, high school,
      clinical, and professional settings.
AB  - Athletes participate at many different levels of competition--from amateur to
      professional, from backyard sandlot to Yankee Stadium. There are as many
      different organized structures involved in providing medical care to athletes as
      there are types of athletes themselves. Although the organizational structures
      involved in providing medical care for a little league team in a small town are
      different from those involved in providing care for a professional baseball team,
      the mission is the same-caring for athletes. This is the central theme of this
      article. Though there are different organizational structures, there are more
      common threads than differences in the mission of those who provide medical care
      for athletes at any level.

PMID- 17499625
TI  - Financial implications of serving as team physician.
AB  - Time is the greatest negative financial burden that you accept as a sports
      medicine physician, because the only way to produce revenue as a physician is
      with your time. This cost measured in time of doing business as a team physician
      can be high. Unless being a team physician is very rewarding to you through
      personal satisfaction or the other intangible indirect benefits associated with
      the role, being a team physician may not be a good financial decision for you as
      a person and a physician, or for your practice and your family.

PMID- 17499626
TI  - Educational opportunities and implications associated with the team physician.
AB  - Teaching is one of the primary responsibilities of the team physician. After all,
      teaching and medicine are inseparable. Educating others is a challenging yet
      essential role of a team physician, and understanding the educational
      opportunities, responsibilities, and methods of creating a learning environment
      are essential qualities of the team physician. The successful teaching team
      physician is the one who accepts his role as an educator, understands the
      importance of involvement in the educational process at all levels, and is able
      to create an environment conducive to student learning, while at the same time
      serving as a valuable resource for patients, coaches, administrators, and the
      public.

PMID- 17499627
TI  - Marketing ideas and strategies for building upon the team physician's role.
AB  - "Show me the money" is without question the number one reason to market and
      advertise. That may sound silly to say, but look at some of the advertising, and
      it will then be time to question and understand the thought process of those who
      advertise and market. In this article, the authors attempt to provide information
      on marketing and advertising that will help your business, and that we hope will
      provide some thought-provoking ideas for you to pursue that will enable you to
      increase your company's bottom line and "show them the money."

PMID- 17499628
TI  - Lessons in sports medicine: advice from experience.
AB  - When addressing the politics of sports medicine, it is often helpful to obtain
      the advice of people who work in the trenches and who have experiences that can
      be of benefit to clinicians in the field or who are contemplating going into the
      field. The goal of this project was to obtain advice from physicians who have
      dealt with these political issues. It is hoped that their insights will prove
      helpful for physicians and others who are involved in the care of athletes,
      regardless of the athlete's level of the play.

PMID- 17499629
TI  - Trends for the future as a team physician: Herodicus to hereafter.
AB  - Much has transpired in the world of sports medicine since Herodicus, a Thracian
      physician of the fifth century BC, rendered his foundational theories on the use
      of therapeutic exercise for the maintenance of health and the treatment of
      disease. Unfortunately, as basic knowledge advances, history abounds in
      inconsistencies in regard to the proper and most effective delivery of sports
      medicine. This article traces the development of sports medicine and its relation
      to high school, college, and Olympic sports over the last centuries, and provides
      glimpses into what the future of the field may hold.

PMID- 17499631
TI  - Automatic behaviour: efficient not mindless.
AB  - Automaticity is a core construct underpinning theoretical accounts of human
      performance and cognition. In spite of this, its current conceptualisation is
      plagued by circularity - automaticity is typically defined in terms of the very
      behaviour it seeks to explain - and a lack of internal consistency-defining
      features of automaticity do not reliably co-occur. Furthermore, invoking
      automaticity tends to be post hoc as it is used to explain violations of dominant
      theories of attention. Prevailing models of automaticity explain automatic
      processing as merely faster processing than controlled processing. We present an
      alternative conceptualisation of automaticity as efficient, elegant and
      economical but not fast. This is supported by functional imaging studies, which
      reveal a pattern of reduced global activation as well as a shift in activation
      from cortical to subcortical areas once automaticity has been achieved. Were
      automaticity to be faster processing, functional imaging would indicate greater
      activation when an automatic task is performed. We propose possible circuitry of
      automaticity incorporating the direct pathways of the basal ganglia.

PMID- 17499630
TI  - Transcriptome analysis of age-, gender- and diet-associated changes in murine
      thymus.
AB  - The loss of thymic function with age may be due to diminished numbers of T-cell
      progenitors and the loss of critical mediators within the thymic
      microenvironment. To assess the molecular changes associated with this loss, we
      examined transcriptomes of progressively aging mouse thymi, of different sexes
      and on caloric-restricted (CR) vs. ad libitum (AL) diets. Genes involved in
      various biological and molecular processes including transcriptional regulators,
      stress response, inflammation and immune function significantly changed during
      thymic aging. These differences depended on variables such as sex and diet.
      Interestingly, many changes associated with thymic aging are either muted or
      almost completely reversed in mice on caloric-restricted diets. These studies
      provide valuable insight into the molecular mechanisms associated with thymic
      aging and emphasize the need to account for biological variables such as sex and
      diet when elucidating the genomic correlates that influence the molecular
      pathways responsible for thymic involution.

PMID- 17499632
TI  - Neuromagnetic dialogue between neuronal minicolumns and astroglial network: a new
      approach for memory and cerebral computation.
AB  - Rapidly accumulating experimental data over the past two decades discloses
      extremely complex neuro-glial interactions and provides new insights regarding
      novel roles of glial cells, particularly astrocytes, in complex functions.
      Widespread astrocytic processes, interconnected by gap junctions, form an
      extremely large physiological syncytium. This structure in conjunction with
      neuronal activity, very likely contributes to cognitive functions. Based on
      electrophysiological and neuroanatomical data, the present hypothesis proposes a
      self-organised, iterative and reciprocal magnetic interaction between neurones
      and astrocytes to explain neurocomputation, including memory processing, in the
      human neocortex.

PMID- 17499633
TI  - Muscarinic cholinoceptors in the ventromedial hypothalamic nucleus facilitate
      tail heat loss during physical exercise.
AB  - The aim of this study was to evaluate the participation of ventromedial
      hypothalamic nucleus (VMH) muscarinic cholinoceptors in heat balance and central
      fatigue during treadmill exercise (24 m min(-1), 5% inclination). The animals
      were anesthetized with pentobarbital sodium (50 mg/kg body weight i.p.) and
      fitted with bilateral cannulae into the VMH 1 week prior to the experiments. Tail
      skin (T(tail)) and core body temperatures (T(b)) were measured after the
      injection of 0.2 microL of 5 x 10(-9) mol methylatropine (Matr) or 0.15 M NaCl
      solution (Sal) into the hypothalamus. Methylatropine injection into the VMH
      greatly increased heat storage rate (HSR) measured until fatigue (19.7+/-4.6 cal
      min(-1) Matr versus 9.7+/-3.3 cal min(-1) Sal; P<0.05) and attenuated the
      exercise-induced tail vasodilation as seen by T(tail) (23.98+/-0.43 degrees C
      Matr versus 25.52+/-0.85 degrees C Sal; at 6.5 min; P<0.05), indicating
      inhibition of the heat loss process. The 2 min delay and the increased DeltaT(b),
      which triggered the heat loss mechanisms observed in Matr-treated rats, are
      associated with increased HSR and may be responsible for the decreased running
      performance of these animals (21.0+/-2.9 min Matr versus 33.5+/-3.4 min Sal;
      P<0.001). In fact, a close negative correlation was observed between HSR and time
      to fatigue (r=-0.61; P<0.01). In conclusion, VMH muscarinic cholinoceptors
      facilitate tail heat loss mechanisms, and a delay in this adjustment would lead
      to a decrease in physical exercise performance due to excess heat storage.

PMID- 17499634
TI  - The kappa-opioid receptor agonist U-69593 prevents cocaine-induced
      phosphorylation of DARPP-32 at Thr(34) in the rat brain.
AB  - DARPP-32 (dopamine- and cAMP-regulated phosphoprotein) is a potent endogenous
      inhibitor of protein phosphatase-1, which plays an important role in dopaminergic
      transmission. A large body of evidence supports the key role of DARPP-32
      dependent signalling in mediating the actions of multiple drugs of abuse,
      including cocaine, which, when acutely administered, increases the Thr(34)
      phosphorylation of DARPP-32 in the striatal and cortical areas. In this study, we
      have examined the contribution of the kappa opioid system to the regulation of
      DARPP-32 phosphorylation at Thr(34), following acute cocaine administration, in
      selected rat brain areas. Results showed that a single injection of cocaine
      induces a significant increase in DARPP-32 phosphorylation at Thr(34) in the
      hippocampus, caudate putamen and prefrontal cortex. In addition, pretreatment
      with the kappa opioid receptor agonist U-69593 prevented cocaine effects in all
      the investigated areas. These data could be considered consistent with the
      ability of kappa opioid agonists to attenuate many behavioural and neurochemical
      effects of cocaine.

PMID- 17499635
TI  - Fronto-parietal networks activation during the contingent negative variation
      period.
AB  - The preparation for stimuli and responses in which the position and required
      finger to respond are cued, produces the preparatory activation of the specific
      neural resources that are going to be needed for the completion of the task. The
      focus of the present report is to evaluate if the fronto-parietal networks
      activated in fMRI studies during endogenous attention are also activated during
      the CNV period using EEG recording. The behavioural responses and 64 EEG channels
      were recorded during an S1-S2 paradigm similar to Posner central cue paradigms.
      The LORETA analysis based in the averaging of the z-LORETA values showed that the
      Brodmann's areas with the highest activation during the CNV period were in the
      medial and superior frontal areas, fronto-parietal lateral areas (including the
      premotor cortex) and extrastriate visual cortex. These results suggest that in
      addition to the previously described activation in premotor-motor, posterior
      sensory and superior and medial frontal areas, the activation of fronto-parietal
      networks is a main contributor to the CNV, indicating the endogenous attentional
      effort during the CNV period.

PMID- 17499636
TI  - Age-related nonhomologous end joining activity in rat neurons.
AB  - DNA double strand break (DSB) represents a potentially lethal form of DNA damage.
      Reports suggest that DSBs are introduced in neurons during the course of normal
      development, and repair of such DSBs is essential for neuronal survival. The
      molecular mechanisms of DSB repair by nonhomologous end joining (NHEJ) have been
      described in several cell types. The present study describes age-related NHEJ
      activity in the isolated neurons from rat cerebral cortex. Cell-free extracts
      prepared from rat cortical neurons support efficient NHEJ of linearized plasmid
      DNA in an in vitro DSB repair assay. End joining efficiency of young neurons is
      dependent on DNA end structure. A linear plasmid with blunt ends was joined less
      efficiently by the neuronal extracts than the cohesive or non-matching protruding
      DNA ends. NHEJ in neurons was blocked by the DNA-PKcs inhibitor wortmannin, and
      dNTP, and could occur in the absence of exogenously added ATP. The end joining
      process in young rat neurons is nonfaithful. In vitro NHEJ activity was
      considerably lower in adult brain, and neurons from old brain failed to support
      significant end joining. The age-dependent profile of neuronal NHEJ indicates
      that neurons in postnatal brain utilize error-prone NHEJ to repair DNA double
      strand breaks accumulated within the genome and this activity declines gradually
      with age.

PMID- 17499637
TI  - Modulation of interleukin-1beta mediated inflammatory response in human
      astrocytes by flavonoids: implications in neuroprotection.
AB  - The proinflammatory cytokine interleukin-1beta (IL-1beta) contributes to
      inflammation and neuronal death in CNS injuries and neurodegenerative
      pathologies, and astrocytes have been implicated as the primary mediators of IL
      1beta induced neuronal death. As astrocytes play an important role in supporting
      the survival and functions of neurons, we investigated the effect of plant
      flavonoids quercetin and luteolin, with known anti-inflammatory properties in
      modulating the response of human astrocytes to IL-1beta for therapeutic
      intervention. Flavonoids significantly decreased the release of reactive oxygen
      species (ROS) from astrocytes stimulated with IL-1beta. This decrease was
      accompanied by an increase in expression of superoxide dismutase (SOD-1) and
      thioredoxin (TRX1)-mediators associated with protection against oxidative stress.
      Flavonoids not only modulated the expression of astrocytes specific molecules
      such as glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and
      ceruloplasmin (CP) both in the presence and absence of IL-1beta but also
      decreased the elevated levels of proinflammatory cytokine interleukin-6 (IL-6)
      and chemokines interleukin-8 (IL-8), interferon-inducible protein (IP-10),
      monocyte-chemoattractant protein-1 (MCP-1), and RANTES from IL-1beta activated
      astrocytes. Significant decrease in neuronal apoptosis was observed in neurons
      cultured in conditioned medium obtained from astrocytes treated with a
      combination of IL-1beta and flavonoids as compared to that treated with IL-1beta
      alone. Our result suggests that by (i) enhancing the potential of activated
      astrocytes to detoxify free radical, (ii) reducing the expression of
      proinflammatory cytokines and chemokines, and (iii) modulating expression of
      mediators associated with enhanced physiological activity of astrocyte in
      response to injury, flavonoids confer (iv) protection against IL-1beta induced
      astrocyte mediated neuronal damage.

PMID- 17499638
TI  - GABA immunoreactivity in the developing rat thalamus and Otx2 homeoprotein
      expression in migrating neurons.
AB  - We investigated the expression of gamma-aminobutyric acid (GABA) in the
      developing rat thalamus by immunohistochemistry, using light, confocal and
      electron microscopy. We also examined the relationship between the expression of
      the homeoprotein Otx2, a transcription factor implicated in brain
      regionalization, and the radial and non-radial migration of early generated
      thalamic neurons, identified by the neuronal markers calretinin (CR) and GABA.
      The earliest thalamic neurons generated between embryonic days (E) 13 and 15
      include those of the reticular nucleus, entirely composed by GABAergic neurons.
      GABA immunoreactivity appeared at E14 in immature neurons and processes laterally
      to the neuroepithelium of the diencephalic vesicle. The embryonic and perinatal
      periods were characterized by the presence of abundant GABA-immunoreactive
      fibers, mostly tangentially oriented, and of growth cones. At E15 and E16, GABA
      was expressed in radially and non-radially oriented neurons in the region of the
      reticular thalamic migration, between the dorsal and ventral thalamic primordia,
      and within the dorsal thalamus. At these embryonic stages, some CR- and GABA
      immunoreactive migrating-like neurons, located in the migratory stream and in the
      dorsal thalamus, expressed the homeoprotein Otx2. In the perinatal period, the
      preponderance of GABAergic neurons was restricted to the reticular nucleus and
      several GABAergic fibers were still detectable throughout the thalamus. The
      immunolabeling of fibers progressively decreased and was no longer visible by
      postnatal day 10, when the adult configuration of GABA immunostaining was
      achieved. These results reveal the spatio-temporal features of GABA expression in
      the developing thalamus and suggest a novel role of Otx2 in thalamic cell
      migration.

PMID- 17499640
TI  - Mismatch negativity analysis in drug-resistant epileptic patients implanted with
      vagus nerve stimulator.
AB  - It is well known that some epileptic patients does not respond to conventional
      treatments, despite multiple combination of antiepileptic drugs, and they are
      therefore considered drug-resistant. For these patients, vagal nerve stimulation
      (VNS) represents a successful alternative to traditional therapy, and it is
      generally well tolerated; beside benefits on seizure frequency, VNS showed
      positive effects on cognition and mood. Aim of this study was to investigate
      short-term memory changes in a group of 12 patients implanted with VNS, through
      Mismatch Negativity wave (MMN). After 1 year of follow-up, MMN latencies and
      amplitudes did not show significant changes following VNS implantation,
      independently on current intensity, as compared with pre-implantation values. In
      two patients, MMN values, which were abnormal before VNS implantation, showed a
      major reduction in latency and an increase in amplitude after implantation,
      suggesting a likely positive effect of VNS on pre-attentive processes
      investigated by MMN.

PMID- 17499639
TI  - Changes in the content of estrogen alpha and progesterone receptors during
      differentiation of mouse embryonic stem cells to dopamine neurons.
AB  - Embryonic stem cells (ESC) can differentiate to derivatives of the three
      embryonic germ layers. Dopamine neurons have been produced from mouse and human
      ESC. This in vitro induction mimics the developmental program followed by
      dopaminergic cells in vivo. Production of dopamine neurons might have clinical
      applications for Parkinson's disease, which has a higher incidence in men than in
      women, suggesting a protective role for sex hormones, particularly progesterone
      and estradiol. These hormones exert many of their effects through the interaction
      with their nuclear receptors. In this study, we used a described 5-stage protocol
      for dopamine neuron differentiation of ESC, allowing neuronal commitment as
      evidenced by specific markers and by behavioural recovery of hemiparkinsonian
      rats after grafting. We studied the expression of steroid hormone receptors by
      immunoblot during this procedure and found an increase in the content of both A
      and B isoforms of progesterone receptor (PR) and a decrease in estrogen receptor
      alpha (ER-alpha) when cells were at the neural/neuronal stages, when compared
      with the amount found in initial pluripotent conditions. We also found the same
      pattern of PR and ER-alpha expression by immunocytochemistry. Ninety-two percent
      of dopamine neurons expressed progesterone receptors and only 19% of these
      neurons co-expressed tyrosine hydroxylase and ER-alpha. These results show a
      differential expression pattern of ER-alpha and PR isoforms during neuronal
      differentiation of ESC.

PMID- 17499641
TI  - Prefrontal cortex and hippocampus in posttraumatic functional recovery: spatial
      delayed alternation by rats subjected to transection of the fimbria-fornix and/or
      ablation of the prefrontal cortex.
AB  - Lesions of the prefrontal cortex and the hippocampus often lead to impairment of
      the same behavioural tasks (e.g., allocentric as well as egocentric spatial
      orientation and spatial delayed alternation). In case of allocentric and
      egocentric spatial orientation we have previously found that the two structures
      mutually contribute to the posttraumatic functional recovery of such tasks. We
      therefore presently tested the hypothesis that this would even be true in case of
      spatial delayed alternation. The acquisition of a spatial delayed alternation
      task in a T-maze was studied in four groups of rats: animals in which the fimbria
      fornix had been transected bilaterally, rats who had received bilateral ablations
      of the anteromedial prefrontal cortex, animals in which both of these structures
      had been lesioned, and a sham operated control group. All three lesion groups
      demonstrated an impaired task acquisition. The group given prefrontal cortical
      lesions in isolation underwent a complete functional recovery. Both of the
      fimbria-fornix transected groups were significantly impaired even when compared
      to the group given prefrontal cortical ablations in isolation. The two fimbria
      fornix lesioned groups did, however, exhibit levels of functional recovery. The
      group in which both structures had been lesioned demonstrated a task acquisition,
      which was significantly inferior to that of the group given fimbria-fornix
      transections in isolation. After completion of the task acquisition period, all
      animals were subjected to two behavioural challenges including a session on which
      the duration of the inter-trial delay was doubled. This expansion of the inter
      trial delay rather selectively impaired the task performance of the group given
      fimbria-fornix transections in isolation. Consequently, both during the
      acquisition period and in one of the challenges a differentiation of functional
      recovery was seen between the combined lesioned group and the group given fimbria
      fornix lesions only. This indicates that even in case of a spatial delayed
      alternation task the prefrontal cortex normally contributes significantly to
      mediation of posttraumatic functional recovery after isolated lesions of the
      fimbria-fornix. The results are discussed in the context of models of
      posttraumatic functional recovery.

PMID- 17499642
TI  - Creativity related cortex activity in the remote associates task.
AB  - The involvement of different oscillating neuronal systems during verbal creative
      thinking was investigated by multi-channel EEG measuring. The remote associates
      task (RAT) as a model of creative thinking in comparison to the resting condition
      and the simple associates task (SAT) was used. The EEG coherence along with
      spectral power density estimates were evaluated in each of the six frequency
      bands in 4-30 Hz range. We have found out RAT-related EEG changes mainly in the
      theta1, alpha1, alpha2 and beta2 bands. The RAT-induced cortical activation was
      differed from the SAT-induced EEG pattern by (i) widespread enhancement of power
      and coherence in the beta2, (ii) the theta1 power increase in the frontal cortex,
      and (iii) increased desynchronization of the alpha1,alpha2 mainly over posterior
      cortex together with the alpha1 coherence decrease in the prefrontal sites.
      Originality scores of the verbal associates positively correlated with an
      increase of coherence focused in the fronto-parietal regions of both hemispheres
      in the beta2 and in the left parieto-temporal loci in the alpha1. Additionally,
      more original responses positively correlated with amplitude of the alpha1 mostly
      in the left hemisphere. We propose that widespread cortical integration of multi
      component internal processing has been simultaneously mediated during creative
      verbal thinking. The selectively distributed theta, alpha, and beta oscillations
      reflect intra- and inter-hemispheric communication networks with different
      functional relations to the RAT solving. The theta1 and alpha1 rhythms seem to
      specifically relate to top-down information processing such as deliberate
      sustained attention and working-memory-retention during defocused attention,
      respectively, whereas larger interregional synchrony in the beta2 band may
      mediate 'differential' attention to diffusely activating alternative meanings of
      words and remote associates from coarse semantic coding.

PMID- 17499643
TI  - Exploratory neuropharmacological evaluation of a conformationally constrained
      thyrotropin-releasing hormone analogue.
AB  - A conformationally constrained peptidomimetic derived from the endocrine and
      neuroactive tripeptide thyrotropin-releasing hormone (pGlu-His-Pro-NH(2)) was
      synthesized by convenient solid-phase organic chemistry and evaluated as a
      potential central nervous system agent. While this ethylene-bridged peptide
      analogue has been reported to lack the hormonal effect of the native peptide, we
      have shown in animal models that it possesses central nervous system activity
      characteristic of thyrotropin-releasing hormone. Compared to control, the
      peptidomimetic showed significant analeptic and antidepressant-like potencies.
      Moreover, an enhanced selectivity in antidepressant-like effect was measured when
      compared to that of the native peptide. Immobilized artificial membrane
      chromatography and in vitro metabolic stability studies also revealed that this
      constrained peptidomimetic has higher affinity to the blood-brain barrier than
      the native peptide and is metabolically stable. Consequently, this structure may
      be used as a template to design centrally selective and metabolically stable
      thyrotropin-releasing hormone analogues as potential neuropharmaceutical agents.

PMID- 17499644
TI  - Gene expression of cyclooxygenase-1 and Ca(2+)-independent phospholipase A(2) is
      altered in rat hippocampus during normal aging.
AB  - Brain aging is associated with inflammatory changes. However, data on how the
      brain arachidonic acid (AA) metabolism is altered as a function of age are
      limited and discrepant. AA is released from membrane phospholipids by
      phospholipase A(2) (PLA(2)) and then further metabolized to bioactive
      prostaglandins and thromboxanes by cyclooxygenases (COX)-1 and -2. We examined
      the phospholipase A(2) (PLA(2))/COX-mediated AA metabolic pathway in the
      hippocampus and cerebral cortex of 4-, 12-, 24- and 30-month-old rats. A two-fold
      increase in brain thromboxane B(2) level in 24 and 30 months was accompanied by
      increased hippocampal COX-1 mRNA levels at 12, 24, and 30 months. COX-2 mRNA
      expression was significantly decreased only at 30 months. Hippocampal Ca(2+)
      independent iPLA(2) mRNA levels were decreased at 24 and 30 months without any
      change in Ca(2+)-dependent PLA(2) expression. In the cerebral cortex, mRNA levels
      of COX and PLA(2) were not significantly changed. The specific changes in the AA
      cascade observed in the hippocampus may alter phospholipids homeostasis and
      possibly increase the susceptibility of the aging brain to neuroinflammation.

PMID- 17499645
TI  - c-FOS and n-NOS reactive neurons in response to circulating Phoneutria
      nigriventer spider venom.
AB  - Drugs and neurotoxins activate specific neural circuits by increasing or
      decreasing the formation and release of neurotransmitters, such as nitric oxide
      (NO), and by inducing immediate early genes, such as FOS. We have previously
      shown that Phoneutria nigriventer spider venom (PNV) impairs the microtubule
      dependent transcellular barrier of the blood-brain interface and causes
      structural alterations in perivascular astrocytic end-feet without producing
      morphological changes in central neuronal cells. In the present study, we used
      FOS and neuronal nitric oxide synthase (n-NOS) immunolabeling to investigate the
      ability of PNV to activate the central nervous system. Three groups of rats were
      used: the first group received a sublethal dose of PNV (850 microg/kg, via a tail
      vein), the second received an equal volume of 0.9% saline (sham group) and the
      third group received no injection. Envenomed rats showed salivation,
      lachrymation, tremors and flaccidity followed by spastic paralysis of the hind
      limbs and convulsions. Cryosections (30 microm thick) were serially collected at
      600 microm intervals for free-floating immunohistochemical analysis. FOS-like
      positive neurons predominated in motor-related areas such as dorsolateral (dlPAG)
      and ventral periaqueductal gray matter (vPAG), frontal (FCM) and parietal motor
      cortex (PCM), and periventricular thalamic nucleus (PTN) and in acute stress
      related areas (rhinal cortex and lateral septal nuclei). The greatest relative
      increases in FOS-like positive neurons occurred in the vPAG, PCM and PTN motor
      related areas. n-NOS-positive neurons predominated in the periventricular
      thalamic nuclei, followed by the dorsolateral periaqueductal gray matter and
      parietal cortex motor area. The marked activation of motor areas and, to a lesser
      extent, of acute stress-related areas suggested the involvement of neuronal
      pathways in these regions in the response to envenoming by PNV. In addition, the
      occurrence of n-NOS immunolabeling in some anatomical regions with FOS-like
      positive neurons suggests that NO may modulate the response to PNV in these
      regions.

PMID- 17499646
TI  - Prolactin secretory surge during estrus coincides with increased dopamine
      activity in the hypothalamus and preoptic area and is not altered by ovariectomy
      on proestrus.
AB  - Prolactin (PRL) secretory surges have been reported on the afternoons of both
      proestrus and estrous in cycling rats. As neuroendocrine regulation of estrous
      PRL surge is poorly understood, the present study aimed to investigate the
      involvement of hypothalamic dopamine and serotonin as well as of plasma ovarian
      steroids in this hormonal surge generation. For that, we determined the
      concentrations of dopamine, serotonin and their respective metabolites 3,4
      dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5-HIAA) in
      the mediobasal hypothalamus (MBH) and medial preoptic area (MPOA) throughout the
      day of estrus and correlated them with plasma PRL levels. In a second study, we
      evaluated the effect of ovariectomy on the morning of proestrus on PRL surges of
      both proestrus and estrus. Dopamine turnover, as determined by DOPAC/dopamine
      ratio, increased in both the MBH and MPOA coinciding with the afternoon PRL surge
      on estrus. In contrast, both the concentration and turnover (5-HIAA/serotonin) of
      serotonin within these areas were unaltered during estrus. In addition,
      ovariectomy reduced plasma estradiol and progesterone levels but did not alter
      the PRL surges on proestrus and estrus. Considering that dopamine is the main
      inhibitor of PRL release and that PRL auto-regulates its secretion through a
      short-loop feedback mechanism, our present results suggest that PRL may suppress
      its own secretion during the estrus surge through the activation of the
      dopaminergic neurons in the MBH and MPOA. In addition, the PRL surge on estrus
      seems do not depend on either the activity of hypothalamic serotonin or the
      increased secretion of ovarian steroids on proestrus.

PMID- 17499647
TI  - Hypertonic shrinking but not hypotonic swelling increases sodium concentration in
      rat brain synaptosomes.
AB  - Neurotransmitter release is dependent on both calcium and sodium influx.
      Hypotonic swelling and hypertonic shrinking of neurons evokes calcium-independent
      exocytosis of neurotransmitters into the synaptic cleft. To date, there are not
      too much data available on relationship between extracellular osmolarity and
      sodium concentration in presynaptic endings. In the present study we investigated
      the effects of hypotonic swelling and hypertonic shrinking on sodium levels, as
      measured using fluorescent dyes SBFI-AM and Sodium Green in rat brain
      synaptosomes. Reduction of incubation medium osmolarity from 310 to 230 mOsm did
      not raise the intrasynaptosomal sodium concentration. An increase of osmolarity
      from 310 to 810 mOsm is accompanied by a dose-dependent elevation of sodium
      concentration from 8.1+/-0.5 to 46.5+/-2.8mM, respectively. This effect was
      insensitive to several channel inhibitors such as: tetrodotoxin, an inhibitor of
      voltage-gated sodium channels, bumetanide, an inhibitor of Na(+)/K(+)/2Cl(-)
      cotransport, gadolinium, an inhibitor of nonselective mechanosensitive channels,
      ruthenium red, an inhibitor of transient receptor potential channel and
      amiloride, an inhibitor of epithelial sodium channel/degenerin. Additionally,
      using the fluorescent dye BCECF-AM, we have shown that hypertonic shrinking
      caused a dose-dependent acidification of intrasynaptosomal cytosol, which
      suggests that the Na(+)/H(+) exchanger is not involved in the effect of increased
      osmolarity on cytosolic sodium levels. The increase in intrasynaptosomal sodium
      concentrations following increases in osmolarity is probably due to sodium influx
      through another sodium channels.

PMID- 17499649
TI  - Fluorescent molecular sensors and multi-photon microscopy in brain studies.
AB  - To clarify the brain phenomena, to prove directly the major biochemical pathways
      in cerebral tissue, and to discover the crucial steps in brain pathology, it is
      necessary to develop a high speed deep-tissue imaging techniques with high
      spatial and temporal resolution, and ultra-fast and highly selective molecular
      sensors, giving a possibility to monitor target molecules directly in their
      physiological environment. This technical comment accents on the perspectives for
      development of direct approach for investigation of function/flow coupling
      phenomenon and zinc transport into the brain, based on the current progress in
      development of ultra-fast molecular sensors for direct visualization of
      biochemical mediators and neurotransmitters, and high speed multi-photon deep
      tissue imaging.

PMID- 17499648
TI  - Measurements of brain-derived neurotrophic factor: methodological aspects and
      demographical data.
AB  - Although numerous studies have dealt with changes in blood brain-derived
      neurotrophic factor (BDNF), methodological issues about BDNF measurements have
      only been incompletely resolved. We validated BDNF ELISA with respect to
      accuracy, reproducibility and the effect of storage and repeated freezing cycles
      on BDNF concentrations. Additionally, the effect of demographic characteristics
      in healthy subjects on BDNF was verified. Whole blood and serum was collected
      from 206 healthy subjects and a subgroup was genotyped for BDNF Val66Met
      polymorphism. The effect of age, gender, BDNF genotype and thrombocyte count on
      whole blood BDNF was assessed. The BDNF ELISA measurement was accurate, 91.6+/
      3.0%, and showed high reproducibility, whereas inter-assay and intra-subject
      variations were modest, 8.4+/-5.2% and 17.5+/-14.1%, respectively. Storage of
      whole blood samples at 4 degrees C significantly decreased BDNF concentration,
      while repeated freezing cycles and storage at -20 degrees C was without any
      effect. Storage at -20 degrees C of serum, but not whole blood, was associated
      with a significant decrease in BDNF concentration. Women had significantly higher
      whole blood BDNF concentrations than men (18.6+/-1.3 ng/ml versus 16.5+/-1.4
      ng/ml), and showed a right-skewed BDNF concentration distribution. No association
      between whole blood BDNF concentrations and thrombocyte count, age, or BDNF
      genotype was found. In conclusion, the BDNF ELISA assay determines whole blood
      BDNF accurately and with high reproducibility. Female gender is associated with
      higher whole blood BDNF concentrations whereas age, thrombocyte count and BDNF
      Val66Met polymorphism were un-associated.

PMID- 17499650
TI  - Genotoxicity of novel trans-platinum(II) complex with diethyl (pyridin-4
      ylmethyl)phosphate in human non-small cell lung cancer cells A549.
AB  - The dynamic development of metal-containing anticancer drugs has started since
      the discovery of cis-diamminedichloroplatinum(II). For many years it was believed
      that trans platinum(II) compounds were non-active as antitumour agents because
      trans-diamminedichloroplatinum is biologically inactive although it binds to DNA
      and also forms monoadducts and cross-links. In the present work the ability of a
      novel platinum(II) compound trans-[PtCl(2)(4-pmOpe)(2)] to induce DNA damage in
      human non-small cell lung cancer cells A549 was examined using the alkaline comet
      assay. The obtained results revealed that the novel trans platinum(II) complex
      induced DNA strand breaks, which were effectively repaired during 2h of post
      incubation, and cross-links which remained unrepaired under these test
      conditions. Apart from that, the modified comet assay with incubation with
      proteinase K was used to verify the ability of trans-[PtCl(2)(4-pmOpe)(2)] and
      cis-DDP to form DNA-protein cross-links. It has been proved that only trans
      [PtCl(2)(4-pmOpe)(2)] complex exhibits the ability to induce DNA-protein cross
      links. The results suggest a different mechanism of action of this compound in
      comparison to cis-DDP. It seems that trans geometry and the presence of two
      diethyl (pyridin-4-ylmethyl)phosphates as non-leaving ligands can determine
      dissimilar properties of the adducts formed on DNA and the different mechanism of
      action of trans-[PtCl(2)(4-pmOpe)(2)] and in consequence the efficacy in killing
      cancer cells.

PMID- 17499652
TI  - A practical selective synthesis of mixed short/long chains
      glycerophosphocholines.
AB  - Glycerophosphorylcholine (GPC) is transformed into the cyclic stannylene
      derivatives, which are selectively acylated to 1-acyl-2-lyso
      glycerophosphocholines. The reaction is effective using C-2 to C-16 acid
      chlorides in 2-propanol. After solvent replacement the lyso-phospholipid (lyso
      PL) is subjected to a second acylation using acid anhydrides in methylene
      chloride. A series of 1(2)-short-2(1)-long-diacyl-glycerophosphocholines are
      obtained in high yields and selectivity. No diacylation product was detected. In
      order to detect mixed-chain lipids with inverted disposition of acyl chains, the
      long chain was introduced first and the thus resulting isomeric compounds
      compared by NMR. An NMR method was developed in order to determine the positional
      purity of the isomeric compounds.

PMID- 17499651
TI  - Intracellular delivery of VIP-grafted sterically stabilized phospholipid mixed
      nanomicelles in human breast cancer cells.
AB  - The purpose of this study was to determine whether biocompatible and
      biodegradable vasoactive intestinal peptide-grafted sterically stabilized
      phospholipid mixed nanomicelles (VIP-SSMM; size, approximately 15 nm), a novel
      nanosized actively targeted drug delivery platform for breast cancer, accumulate
      in human MCF-7 breast cancer cells. Using hydrophobic CdSe/ZnS quantum dots (QD),
      we found that QD-loaded VIP-SSMM accumulated significantly faster and in greater
      quantity in MCF-7 cells than did QD-loaded SSMM alone (p<0.05). This process was
      mediated, in part, by VIP receptors because excess human VIP, but not PACAP(6-38)
      or galanin, significantly attenuated this response (p<0.05). Taken together,
      these data indicate that VIP-SSMM are actively targeted to human breast cancer
      cells through VIP receptors. We suggest that VIP-SSMM could be used as an
      actively targeted nanosized drug delivery platform for breast cancer cells over
      expressing VIP receptors.

PMID- 17499653
TI  - Expanding the use of topical anesthesia in wound management: sequential layered
      application of topical lidocaine with epinephrine.
AB  - Topical anesthesia eliminates the need for injection of anesthetic. Most studies
      on the use of topical anesthesia were done on children, using 3 active
      ingredients (lidocaine, epinephrine, tetracaine, or tetracaine, adrenaline,
      cocaine) for relatively small wounds of the face and scalp. OBJECTIVES: To
      demonstrate that topical anesthesia is effective and safe in adults of all ages
      and for larger wounds, using a preparation with 2 active ingredients, topical
      lidocaine and epinephrine (TLE). METHODS: One hundred patients were enrolled in a
      randomized controlled trial, with 50 in each group. The study group received TLE
      using a unique method of "sequential layered application." The control group
      received 2% lidocaine infiltration anesthesia. Patients rated the pain from the
      application of anesthesia and from suturing, using a 0 to 10 visual analog pain
      scale. Follow-up interviews were conducted to assess for complications and to
      rate patients' wound repair experience. RESULTS: Patients in the study group
      reported significantly less pain from TLE application, with 66% reporting no pain
      vs 0% reporting no pain from the infiltration in the control group (P < .001).
      There was no difference in pain during wound repair between the 2 groups (P
      approximately .59). On follow-up, 95% of patients contacted in the TLE group
      rated their experience in regard to pain as "excellent," compared to 5% of
      patients in the control group (P < .001). CONCLUSION: Topical lidocaine and
      epinephrine "sequential layered application" is an effective, safe, and less
      painful method of anesthesia for a wide variety of lacerations. Patients recall
      their experience with this technique very favorably.

PMID- 17499654
TI  - Management of severe acute pain in emergency settings: ketamine reduces morphine
      consumption.
AB  - OBJECTIVE: The aim of the study was to compare in emergency settings 2 analgesic
      regimens, morphine with ketamine (K group) or morphine with placebo (P group),
      for severe acute pain in trauma patients. METHODS: This was a prospective,
      multicenter, randomized, double-blind, clinical trial. Seventy-three trauma
      patients with a severe acute pain defined as a visual analog scale (VAS) score of
      at least 60/100 were enrolled. Patients in the K group received 0.2 mg x kg(-1)
      of intravenous ketamine over 10 minutes, and patients in the P group received
      isotonic sodium chloride solution. In both groups, patients were given an initial
      intravenous morphine injection of 0.1 mg x kg(-1), followed by 3 mg every 5
      minutes. Efficient analgesia was defined as a VAS score not exceeding 30/100. The
      primary end points were morphine consumption and VAS at 30 minutes (T30).
      RESULTS: At T30, morphine consumption was significantly lower in the K group vs
      the P group, with 0.149 mg x kg(-1) (0.132-0.165) and 0.202 mg x kg(-1) (0.181
      0.223), respectively (P < .001). The VAS score at T30 did not differ
      significantly between the 2 groups, with 34.1 (25.6-42.6) in the K group and 39.5
      (32.4-46.6) in the P group (P = not significant). CONCLUSION: Ketamine was able
      to provide a morphine-sparing effect.

PMID- 17499655
TI  - The value of serum tau protein for the diagnosis of intracranial injury in minor
      head trauma.
AB  - OBJECTIVE: Tau protein localizes in the axons of neuron cells, and it is released
      secondarily from the central nervous system because of hypoxia and trauma. In the
      present study, it was aimed to investigate the value of serum tau protein levels
      in diagnosing intracranial pathologies in minor head trauma. METHODS: Patients
      were categorized into 2 groups: those without intracranial lesions in head CTs
      (group 1) and those with lesions in head CTs (group 2). Serum tau protein levels
      were determined. RESULTS: Group 1 (n = 55) median serum tau protein level was
      16.29 pg/mL (2.12-215.97 pg/mL) and group 2 (n = 33) median serum tau protein
      level was 18.39 pg/mL (2.19-714.47 pg/mL). Statistical analysis revealed no
      significant difference between the 2 groups for tau protein values, sex, age,
      mechanism of trauma, and Glasgow Coma Scale score. CONCLUSION: It is suggested
      that serum tau protein has limited value in minor head trauma.

PMID- 17499656
TI  - Frequency of radiology self-referral in abdominal computed tomographic scans and
      the implied cost.
AB  - Concerns over rising imaging costs have led to the consideration by Medicare to
      limit the ability of clinicians to bill for image interpretation. This move has
      often been justified as a method to limit self-referral. However, clinicians may
      not be the only ones capable of referring imaging business to themselves.
      OBJECTIVE: This study was conducted to evaluate the frequency and potential cost
      of self-referral by radiologists found in dictated reports of abdominal computed
      tomographic (CT) scans for emergency patients. METHODS: A retrospective chart
      review of all abdominal CTs performed at a level 1 academic urban emergency
      department (ED) with an annual census of 80,000 patients for a 12-month period
      was performed. Two investigators reviewed the medical record dictation on each
      abdominal CT performed on ED patients older than 18 years, for specific
      recommendations for additional radiologic testing. To check for agreement, both
      investigators reviewed approximately 20% of the charts. Recommended additional
      radiologic tests were recorded, and their costs were estimated by the lowest
      regional Medicare reimbursements for each test; professional and facilities fees
      were combined. Statistical methodology included descriptive statistics and
      interrater agreement. RESULTS: A total of 785 reports of abdominal CTs were
      reviewed. Of these reports, 246 (31%) specifically recommended an additional
      imaging study be obtained for a specific finding. In 38 (5%) cases, 2 separate
      imaging studies were suggested. The total lowest cost for additional imaging
      among all of the patients studied was $58,157. The mean suggested charge per
      patient with additional imaging self-referral was $242.32. The additional
      suggested imaging averaged to $74.09 (95% confidence interval, 63.67-84.50) for
      each patient receiving an abdominal CT scan in the ED. The largest suggested cost
      was $1045. Extrapolation to a national level means that more than $226 million of
      additional costs are seen annually from such CTs. No attempt was made to evaluate
      the appropriateness of the suggested imaging. CONCLUSIONS: A type of radiology
      self-referral is possible and can add considerable cost to patient care. In our
      study, an average of $74 of extra imaging was suggested for each patient who
      received an abdominal CT. If this holds up nationwide, Medicare can expect at
      least $226 million worth of radiology self-referrals per year on patients getting
      abdominal CT.

PMID- 17499657
TI  - Prehospital use of analgesics at home or en route to the hospital in children
      with extremity injuries.
AB  - PURPOSE: The purpose of the study was to document prehospital analgesia (PA) for
      children with extremity injuries at home or en route to the hospital, as assessed
      by research personnel at the pediatric emergency department. METHODS: Two
      parallel groups of patients with fractures or soft-tissue injuries (STIs) were
      chosen for this prospective observational study. Patients 3 to 18 years of age
      with a limb or clavicle injury were enrolled. Parents or children were
      interviewed, pain assessed, and data from the emergency department charts
      collected. RESULTS: A total of 310 patients were recruited; their mean age was
      10.2 years, and 62% had fractures. The median pain score was 4.0, with no
      significant difference between fractures and STI. Of the patients, 78% had PA,
      73% received first aid (icing, immobilization), and 37% had medication, mostly
      acetaminophen and ibuprofen. Children with fractures and STI received PA at a
      similar rate; however, the time to first aid was shorter in those with fractures.
      CONCLUSION: Most patients with moderate or severe pain did not receive
      prehospital pain medication. Parental education and moderate over-the-counter
      analgesics are needed for better pain relief.

PMID- 17499658
TI  - A risk score to predict silent myocardial ischemia in patients with coronary
      artery disease under aspirin therapy presenting with upper gastrointestinal
      hemorrhage.
AB  - BACKGROUND: Silent myocardial ischemia (SMI) is a relatively common complication
      in patients with coronary artery disease (CAD) under aspirin therapy presenting
      with upper gastrointestinal hemorrhage (UGIH). AIM: This study was conducted to
      develop and prospectively validate a risk prediction score to identify SMI in
      patients undergoing aspirin therapy for CAD presenting with UGIH in the emergency
      department (ED). METHODS: This was a 2-phase noninterventional study. In the
      derivation phase, adults with CAD under aspirin therapy (100 mg once daily)
      presenting to the ED with UGIH were retrospectively recruited. By multiple
      logistic regression analysis, we derived a risk score from 224 patients that
      predicts the patients' risk of SMI. In the validation phase, we prospectively
      validated this score using receiver operating characteristic curves with data
      from 110 patients. We also developed a fast-track screening procedure from this
      score. RESULTS: There were 56 patients (25.0%) and 29 patients (26.4%) with SMI
      in the derivation and validation sets, respectively. Independent multivariate
      predictors of SMI were age of older than 75 years, severity of CAD, systolic
      blood pressure of less than 110 mm Hg, diastolic blood pressure of less than 85
      mm Hg, hematocrit of less than 30%, and blood urea nitrogen-creatinine ratio of
      more than 30. The area under receiver operating characteristic curve for the rule
      was 0.93 in the derivation set and 0.96 in the validation set. At the cutoff
      value of 5 points or higher, the sensitivity and specificity of the fast-track
      screening procedure for SMI were 96.6% and 86.4%, respectively. The positive and
      negative predictive values were 71.8% and 98.6%, respectively. CONCLUSIONS: This
      simple risk prediction score is easily calculated and is based on rapidly
      available clinical and laboratory data in the ED. It can be used to stratify
      patients undergoing aspirin therapy for CAD presenting with UGIH by risk of SMI.

PMID- 17499659
TI  - A clinical score predicting the need for hospitalization in scorpion
      envenomation.
AB  - OBJECTIVE: Predicting complications is a clinical challenge in the assessment of
      victims of scorpion envenomation (SE). We sought to develop a clinical score to
      predict need for hospitalization after scorpion sting. METHODS: We prospectively
      collected data in patients attending the emergency department after SE in
      derivation (n = 868) and validation groups (n = 435). A score was derived from a
      multiple regression analyses using clinical variables as dependent variables and
      hospitalization as independent variable. RESULTS: Discrimination power of the
      constructed score was good (area under the receiver operating characteristic
      curve, 0.85 and 0.83 in derivation and validation group, respectively). Goodness
      of-fit tests indicated that the score performed well in the derivation and the
      validation groups (P = .88 and P = .67 respectively). The score has a good
      sensitivity and negative predictive value at cutoff value of 2. CONCLUSION: Our
      clinical score could be used for efficient hospital admission decision in
      patient's victims of SE.

PMID- 17499660
TI  - External cardiac defibrillation during wet-surface cooling in pigs.
AB  - OBJECTIVE: During surface cooling with ice-cold water, safety and effectiveness
      of transthoracic defibrillation was assessed. METHODS: In a pig ventricular
      fibrillation cardiac arrest model, once (n = 6), defibrillation was done first in
      a dry and then in a wet condition using the ThermoSuit System (Life Recovery
      Systems, HD, LLC, Kinnelon, NJ), which circulates a thin layer of ice-cold water
      (approximately 4 degrees C) over the skin surface. Another time (n = 6),
      defibrillation was done first in a wet and then in a dry condition. Success of
      defibrillation was defined as restoration of spontaneous circulation, and the
      current and voltage of the defibrillation signal was measured. RESULTS: There was
      a tendency toward less number of shocks needed for achieving restoration of
      spontaneous circulation in the wet condition as compared with the number of
      shocks needed in the dry condition. The energy delivered in both dry and wet
      conditions was 144 +/- 3 J. DISCUSSION: Transthoracic defibrillation is safe and
      effective in a wet condition after cooling with ice-cold water.

PMID- 17499661
TI  - Clinical measures associated with FEV1 in persons with asthma requiring hospital
      admission.
AB  - OBJECTIVE: We sought to determine the association of select clinical measures of
      asthma severity with percent predicted forced expiratory volume in one-second
      (%FEV1). METHODS: We studied a prospective cohort of adult subjects (N = 129)
      with asthma exacerbations requiring hospital admission. Clinical data was
      acquired, including medical and social history, symptoms, vital signs, physical
      assessment, and spirometry. Predictor variables for this study included manually
      determined pulsus paradoxus (PP), percent predicted peak expiratory flow rate
      (%PEFR) and accessory muscle use. The outcome measure was %FEV1. Multiple linear
      regression analyses were performed to determine the independent associations
      between predictor variables and %FEV1. RESULTS: In univariate analysis, %PEFR
      correlated with %FEV1 (rho = 0.77, P < .001) and PP correlated negatively with
      %FEV1 (rho = - 0.384, P < .001). %FEV1 was significantly lower in participants
      with accessory muscle use (Median %FEV1 = 37.5%, IQR: 27.0-49.0) than in those
      without accessory muscle use (Median %FEV1= 55.0%, IQR: 39.0-69.0), (P = .004).
      In multivariable analysis including the covariates %PEFR, accessory muscle use,
      PP, age, sex, heart rate and respiratory rate, %PEFR (P < .0001) and accessory
      muscle use (P = .003) remained significantly associated with %FEV1, whereas PP
      did not (P = .52).

PMID- 17499662
TI  - Splenic artery aneurysms encountered in the ED: 10 years' experience.
AB  - OBJECTIVE: Our objective was to report 7 cases of splenic artery aneurysm (SAA)
      encountered in the emergency department (ED). METHODS: A retrospective survey of
      our ED database revealed 7 cases of SAA (6 men, 1 woman; mean age, 56 years) of
      651,347 ED visits over the last decade. Their clinical and imaging features,
      management, and outcomes were evaluated. RESULTS: Splenic artery aneurysm in the
      ED was rare (prevalence, 0.011%). Common presentations included acute abdomen (n
      = 5) and shock (n = 2). Five cases had liver cirrhosis and portal hypertension.
      Abdominal radiographs (n = 7) revealed 2 atherosclerotic patients with SAA.
      Abdominal computed tomography (n = 7) depicted all SAAs (size, 1.5-8 cm; mean,
      3.8 cm). Four ruptured SAAs were successfully managed with coils embolization.
      Among them, 1 patient with ruptured mycotic SAA also received surgery, but the
      patient died of Klebsiella sepsis 3 months later. CONCLUSIONS: In the ED,
      ruptured SAA should be included as a rare differential consideration of acute
      abdomen, especially in middle-aged men with liver cirrhosis and portal
      hypertension. Although SAA may be an unexpected computed tomographic finding,
      once diagnosed, endovascular treatment is recommended.

PMID- 17499663
TI  - Utility of impedance cardiography for dyspneic patients in the ED.
AB  - BACKGROUND: Dyspnea is one of the most common emergency department (ED) symptoms,
      but early diagnosis and treatment are challenging because of multiple potential
      causes. Hemodynamic parameters may aid in the evaluation of dyspnea, but are
      difficult to assess. Impedance cardiography is a noninvasive hemodynamic
      measurement method that may assist in early ED decision making. METHODS: This
      study is intended to determine the accuracy in differentiating cardiac from
      noncardiac causes of dyspnea using impedance cardiography-derived hemodynamic
      parameters compared to ED physician opinion in light of initial history, and
      physical and laboratory tests. The final diagnosis, made after patient hospital
      record review, was compared with ED physician and impedance cardiography
      diagnoses. RESULTS: A total of 52 patients were included: 14 women and 38 men,
      aged 68.5 +/- 14.2 years. There were significant differences in values of stroke
      index (25.7 vs 32.9, P < .05), cardiac index (2.3 vs 3.1, P < .0001), velocity
      index (35.1 vs 53.2, P < .01), and systolic time ratio (0.55 vs 0.44, P < .05)
      between the cardiac and noncardiac groups, respectively. Impedance cardiography
      measurements demonstrated better sensitivity (75% vs 60%), specificity (88% vs
      66%), and positive and negative predictive values (79% vs 52% and 85% vs 72%,
      respectively) compared with those of the ED physician in distinguishing cardiac
      from noncardiac causes of dyspnea. CONCLUSION: Impedance cardiography data result
      in improvement in ED physician differentiation of cardiac from noncardiac causes
      of dyspnea.

PMID- 17499664
TI  - Outcomes after environmental hyperthermia.
AB  - OBJECTIVES: This study was conducted to describe the characteristics and outcomes
      of patients who presented to the emergency department (ED) with presumed
      environmental hyperthermia. METHODS: A retrospective chart review was performed
      in 2 institutions with patients who were seen in the ED and had a discharge
      diagnosis of hyperthermia, heat stroke, heat exhaustion, or heat cramps.
      Exclusion criteria were an alternative diagnosis potentially explaining the
      hyperthermia (pneumonia, etc). Research assistants, who were blinded to the
      purpose of the study, performed a systematic chart review after a structured
      training session. If necessary, a third reviewer acted as a tiebreaker. Data
      regarding patient demographics, comorbidities, vital signs, laboratory results,
      and short-term outcome were collected. Data were analyzed with Excel and STATA
      software. RESULTS: We enrolled 52 patients with a mean age of 42.6 years (range,
      0.4-81 years) from August 1, 2003 to August 31, 2005. The mean high daily
      temperature was 103.6 degrees F (range, 88-118 degrees F). At presentation, the
      mean body temperature was 105.1 degrees F (range, 100.2-111.2 degrees F) and the
      Glasgow Coma Scale score was less than 14 in 36 (69.2%) patients. Laboratory
      results demonstrated that 21 (40.4%) patients had a creatinine level of more than
      1.5 mg/dL, 35 (67.3%) patients had a creatine kinase (CK) of more than 200 U/L,
      30 patients (57.7%) had a prothrombin time of more than 13 seconds, 29 (55.8%)
      patients had an aspartate aminotransferase (AST) of more than 45 U/L, and only 3
      patients (5.7%) had a glucose of less than 60 mg/dL. Ethanol or illicit drugs
      were involved in 18 (34.6%) cases. The mean hospital stay was 4.7 days (range, 1
      30 days), and there were 15 deaths (28.8%). A kappa score for interreviewer
      reliability was 0.69. Major limitations were the retrospective nature and lack of
      homogeneity in patient evaluation and test ordering. CONCLUSIONS: Hyperthermic
      patients with higher initial temperatures, hypotension, or low Glasgow Coma Scale
      score were more likely to die.

PMID- 17499665
TI  - Effectiveness of nonnarcotic protocol for the treatment of acute exacerbations of
      chronic nonmalignant pain.
AB  - INTRODUCTION: Emergency department (ED) overcrowding is a growing problem.
      Frequent visits for chronic pain are a significant subset of patients. The use of
      narcotics in these patients is controversial. The purpose of this study was to
      test a strict nonnarcotic protocol in reducing need for and number of ED visits
      for chronic pain while at the same time addressing their pain. METHODS: This was
      a prospective observational study. We identified patients with more than 10 ED
      visits for exacerbations of chronic nonmalignant pain in the last 12 calendar
      months. Each patient and their physician were sent letters informing them of the
      concern of frequent ED use and the use of opioids for rescue therapy.
      Furthermore, the patient would receive medications other than narcotics in
      subsequent ED visits, and follow-up with the primary physician for alternatives
      was encouraged. Use of the ED for pain-related visits was then monitored for the
      subsequent 12-month period. Clinic use and outpatient medication uses were also
      monitored. RESULTS: Fifteen patients were identified for the initial study. These
      patients averaged 19 ED visits per 12 months for pain-related complaints. All of
      them had a regular physician. After notification of the new protocol, ED visits
      decreased to an average of 2 visits per year. Visits with primary care physicians
      also dropped from an average of 19 visits per year to 7 visits. There were 7
      patients who had been weaned off narcotic medications, 4 who had been converted
      to methadone maintenance, and 1 who had been switched to a fentanyl patch.
      CONCLUSIONS: Initiation of a strict nonnarcotic protocol for treatment of
      patients with frequent ED visits for chronic nonmalignant pain results in a
      significant drop in the number of pain-related visits to the ED. These visits
      were not offset by a significant elevation in the number of clinic visits for
      pain complaints, and many were weaned off narcotics. Nonnarcotic protocols for
      acute exacerbations of chronic nonmalignant pain may be a viable alternative for
      reducing frequent pain-related ED visits in a select population.

PMID- 17499666
TI  - Sixty-four-slice multidetector computed tomography: the future of ED cardiac
      care.
AB  - Multidetector computed tomography (MDCT) imaging, a technological advance over
      traditional CT, is a promising possible alternative to cardiac catheterization
      for evaluating patients with chest pain in the emergency department (ED). In
      comparison with traditional CT, MDCT offers increased spatial and temporal
      resolution that allows reliable visualization of the coronary arteries. In
      addition, a "triple scan," which includes evaluation for pulmonary embolism and
      thoracic aortic dissection, can be incorporated into a single study. This test
      will enable emergency physicians to rapidly evaluate patients for life
      threatening illnesses and may allow safer and earlier discharges of many patients
      with chest pain in comparison with a traditional rule-out protocol. In this
      article, we will highlight the technological advances of MDCT imaging, review the
      literature on coronary angiography via MDCT, and discuss the future of this
      technology as it relates to the ED.

PMID- 17499667
TI  - Broad complex atrial fibrillation.
AB  - The management of broad complex atrial fibrillation is complex and may be a
      source of morbidity and mortality if not correctly recognized and treated
      appropriately. We present a case series of 3 patients who were managed in our
      emergency department after complaints of palpitations. They presented with
      varying forms of rapid atrial fibrillation that had broad complexes on the 12
      lead electrocardiogram. The first 2 patients were treated with calcium channel
      blockers for rate control, and treatment was complicated by rapid arrhythmia that
      required cardioversion. The final patient was correctly treated with intravenous
      procainamide. The diagnosis of Wolff-Parkinson-White syndrome was eventually made
      in all these patients. Broad complex atrial fibrillation must be treated with
      respect. Cases with rapid ventricular rate can decompensate from mismanagement
      due to poor ability to recognize the possibility of Wolff-Parkinson-White
      syndrome in such patients. Procainamide forms the cornerstone of treatment in
      hemodynamically stable rapid broad complex atrial fibrillation of unknown origin.

PMID- 17499668
TI  - The VIDAS D-dimer test for venous thromboembolism: a prospective surveillance
      study shows maintenance of sensitivity and specificity when used in normal
      clinical practice.
AB  - BACKGROUND: As a result of a number of clinical management studies, D-dimer (DD)
      tests such as VIDAS (BioMerieux Australia P/L-Sydney, NSW) have been recommended
      to reduce venous thromboembolism (VTE) investigations. Surveillance studies for
      new tests are recommended. We prospectively assessed VIDAS DD in normal practice.
      METHODS: Consecutive emergency patients and inpatients (IPs) with DD or VTE
      investigations were prospectively identified. Investigation results and early
      chart review including predefined factors reducing specificity were documented. A
      latex DD was also performed. Patients were followed for at least 3 months for
      recurrent VTE. RESULTS: Four hundred three patients (emergency, 64%; VTE
      positive, 12%; 95% followed up) were analyzed. VIDAS sensitivity was 96% (95%
      confidence interval 86%-99%), specificity 38% (confidence interval, 34%-44%;
      negative likelihood ratio, 0.11), and emergency specificity 51%. Latex
      sensitivity was 76%. Cancer, trauma, recent operations, IP status, and advanced
      age were associated with markedly reduced specificity. Specificity in older
      emergency patients (>70 years old) and younger IPs (<70) without comorbidities
      was 20% to 30%, but sensitivity was maintained at 100%. CONCLUSIONS: VIDAS DD
      probably maintains adequate sensitivity in normal clinical practice for low- or
      even intermediate-risk patients. Latex agglutination had poor sensitivity.
      Specificity is best in younger low-morbidity emergency patients. These findings
      need validation in larger multicenter surveillance studies.

PMID- 17499669
TI  - Ultrasound-guided supraclavicular block for the treatment of upper extremity
      fractures, dislocations, and abscesses in the ED.
AB  - Emergency department (ED) patients with fractures, dislocations, or abscesses of
      the upper extremities often require closed reduction or incision and drainage to
      treat these conditions. Procedural sedation is often necessary when infiltration
      of local anesthetic provides insufficient analgesia. Anesthesiologists commonly
      perform supraclavicular brachial plexus nerve blocks to achieve analgesia for
      upper extremity surgery. We report a series of 5 ED patients in whom
      supraclavicular brachial plexus nerve blocks using real-time ultrasound guidance
      provided excellent analgesia and obviated the need for procedural sedation.

PMID- 17499670
TI  - The use of long-term controller medications in asthmatic patients being
      discharged from the ED--why the controversy?

PMID- 17499671
TI  - Therapeutic hypothermia and the need for defibrillation: wet or dry?

PMID- 17499672
TI  - Infantile case of seizure induced by intoxication after accidental consumption of
      eperisone hydrochloride, an antispastic agent.

PMID- 17499673
TI  - Obtundation in a toddler: naloxone is fundamental.

PMID- 17499674
TI  - Hydronephrosis during pregnancy.

PMID- 17499675
TI  - Recurrent myelin basic protein elevation in cerebrospinal fluid as a predictive
      marker of delayed encephalopathy after carbon monoxide poisoning.

PMID- 17499676
TI  - Reply to Multiple-dose activated charcoal in carbamazepine poisoning.

PMID- 17499677
TI  - Reply to Proper observation of patient related factors is an important
      determinant in the utility of the D-dimer test for exclusion of venous
      thromboembolism in the ED.

PMID- 17499678
TI  - Emergency short-stay unit as an effective alternative to in-hospital admission
      for acute chronic obstructive pulmonary disease exacerbation.

PMID- 17499679
TI  - Differences between various glomerular filtration rate calculation methods in
      predicting patients at risk for contrast-induced nephropathy.

PMID- 17499680
TI  - Traumatic inferior gluteal artery pseudoaneurysm: case report and review of
      literature.

PMID- 17499681
TI  - Acute emphysematous cholecystitis with initial normal radiological evaluation: a
      fatal diagnostic pitfall in the ED.

PMID- 17499682
TI  - Preanalytical influences on the measurement of visfatin by enzyme immuno assay.

PMID- 17499683
TI  - Kurtosis provides a good omnibus test for outliers in small samples.
AB  - OBJECTIVES: To compare the power of the Healy, single-outlier Grubbs, skewness
      and kurtosis tests for outliers and their applicability to quality control (QC).
      DESIGN AND METHODS: Power to detect outliers was calculated in simulated samples
      of twenty normal variates, one or two of which were shifted in mean or increased
      in variance. RESULTS: All tests showed similar power against a single outlier.
      For two outliers shifted in the same direction, skewness then kurtosis were the
      most powerful; for outliers shifted in opposite directions, Healy's method was
      just superior to kurtosis. For two outliers of increased variance, these two
      methods were first equal. CONCLUSIONS: Where the number of outliers is unknown
      the kurtosis test for outliers is more versatile than the Grubbs test as it has
      greater power where there is more than one outlier, a similar power when there is
      just one outlier, and a similar performance in QC.

PMID- 17499684
TI  - Strategies for dealing with emergency department overcrowding: a one-year study
      on how bedside registration affects patient throughput times.
AB  - The objective of this study was to determine if the implementation of bedside
      registration would affect patient throughput times in an urban, academic
      emergency department. This was a before-and-after interventional study. An 8
      month period before initiating bedside registration in November 2001 was compared
      to three subsequent 4-month intervals. Four times of day and three triage
      classifications were examined. Data were analyzed using a three-way analysis of
      covariance. There were 58,225 patient encounters analyzed. There was a
      significant difference in time from triage to room after bedside registration
      began (p < 0.0001). When examined by triage class, there were no differences in
      triage-to-room for emergent patients, a significant decrease for urgent patients
      initially and a significant decrease for non-urgent patients. Bedside
      registration by time of day initially reduced all four time-of-day periods but
      over the year they returned to pre-bedside registration levels, except for the
      morning period. Bedside registration decreased triage-to-room times for non
      urgent patients and urgent patients initially, but this was not sustained at the
      end of 1 year. It had no effect on emergent patients who are routinely taken into
      the patient care area immediately. The sustainable effects of bedside
      registration were during the morning time when emergency department beds were
      available.

PMID- 17499685
TI  - Predicting endotracheal tube size by length in newborns.
AB  - The objective of this study was to determine the relationship of length to
      endotracheal tube (ETT) size in newborns and to use this relationship to develop
      a tool for predicting ETT size. The study, a prospective derivation, and
      validation of a predictive model, took place in the neonatal intensive care units
      (NICUs) in two urban teaching hospitals. Subjects included: ETT derivation set -
      39 intubated neonates admitted to the NICU; Validation set - 69 intubated
      newborns from the same NICU. Leak percentages were measured in intubated neonates
      where the actual ETT size did not correlate with the tape-determined ETT size.
      Interventions were length, weight, and leak measurements. A prototype tape was
      developed using the derivation set and published anthropometric studies. The
      accuracy of the tape was validated on a separate set of newborns. The average
      relative difference between tape-predicted weight and actual weight was 9.5%
      (confidence interval [CI] = 8.3-10.6%) and was evenly distributed throughout all
      the weight groups. The tape predicted actual ETT size in 96% of cases (CI 86.3
      99.5%) and was correct within 1 tube size (1/2 mm) in 100% (CI 94.8-100%). The
      only error in prediction of ETT size was in underestimation. Length-based weight
      estimations were tested on 100 subjects and predicted actual weight within 20% in
      94% of cases. We concluded that length is an accurate predictor of ETT size and
      weight in term and preterm newborns and may be useful in situations in which
      weights are unobtainable, such as emergency resuscitation.

PMID- 17499687
TI  - Non-aneurysmal infectious aortitis: a case report.
AB  - Infectious aortitis is a rare clinical entity that is most often associated with
      an abdominal aortic aneurysm. There have been very few documented cases of
      aortitis in the setting of a normal-sized caliber aorta. We present a 67-year-old
      patient who presented to our Emergency Department with a history of recent
      fevers, fatigue, and abdominal pain. Based on an abdominal computed tomography
      scan, the patient was initially thought to have ruptured an abdominal aortic
      aneurysm of infectious etiology with extension into the left psoas muscle.
      Explorative laparotomy, however, revealed an infected abdominal aorta secondary
      to a retroperitoneal abscess with no evidence of aneurysm or pseudoaneurysm. The
      pathophysiology of the disease suggests that infectious aortitis and mycotic
      aneurysm represent extremes along a spectrum of the same disease. Establishing a
      diagnosis of aortic infection before the formation of an aneurysm or rupture is
      very difficult, but essential in preventing the devastating complications.

PMID- 17499686
TI  - Factors associated with antimicrobial resistance and mortality in pneumococcal
      bacteremia.
AB  - We conducted a multicenter, retrospective cohort study of patients with
      Streptococcus pneumoniae bacteremia to determine factors associated with
      antibiotic resistance and mortality. Risk factors were identified using
      multivariate logistic regression. There were 1574 patients at 34 sites enrolled.
      Compared to isolates from patients not receiving an antibiotic before the index
      blood culture, patients receiving an antibiotic were less likely to harbor an
      antibiotic susceptible organism. Susceptibility to penicillin decreased from 78%
      (95% confidence interval [CI] 75-80) to 49% (95% CI 39-59); to
      cefotaxime/ceftriaxone, from 92% (95% CI 90-93) to 82% (95% CI 72-89); and to
      macrolide, from 84% (95% CI 82-87) to 55% (95% CI 41-68). Factors associated with
      macrolide non-susceptibility include: > 24 h of antibiotic therapy at time of the
      index culture (odds ratio [OR] 4.0), residing in southern U.S. (OR 1.7), and
      having an antibiotic allergy (OR 1.7). Harboring an antibiotic non-susceptible
      strain (OR 1.4) and male sex (OR 1.4) were associated with increased risk of
      mortality, whereas black race (OR 0.6) and evidence of focal infection (OR 0.6)
      were associated with decreased risk.

PMID- 17499688
TI  - Lemierre's syndrome complicating bacterial pharyngitis in a patient with
      undiagnosed factor XII deficiency.
AB  - Internal jugular vein thrombosis occurs as an uncommon complication of
      oropharyngitis. The following case report describes a previously healthy adult
      woman who presented with sore throat, left ear pain, and fever. She was initially
      diagnosed with pharyngitis and inadvertently had blood cultures sent as part of
      her workup. She was then called back to the Emergency Department the following
      day for positive growth of the blood culture, and found to have thrombophlebitis
      of the internal jugular vein on computed tomography scan of the neck. Further
      workup revealed factor XII deficiency. The clinical course was further
      complicated by septic pulmonary emboli and disseminated intravascular
      coagulation. The patient was treated with broad-spectrum antibiotics and
      anticoagulation and made a full recovery.

PMID- 17499689
TI  - Spontaneous intracranial hypotension: case report and relevant review of the
      literature.
AB  - Spontaneous intracranial hypotension (SIH) is a well-defined clinical entity that
      is frequently misdiagnosed because little information regarding this type of
      headache exists in the Emergency Medicine literature. This report presents a case
      and relevant review of the literature on SIH. An understanding of the
      characteristic symptomatology, appropriate evaluation, treatment options, and
      prognosis is essential if the emergency physician is to provide the most
      appropriate care to these patients.

PMID- 17499690
TI  - Intracranial cholesteatoma: a case report and review.
AB  - A cholesteatoma can be a complication of ear infection, eustachian tube
      dysfunction, prior ear surgery, or tympanic membrane perforation. It is typically
      associated with otorrhea and conductive hearing loss; sensorineural hearing loss,
      dysequilibrium, facial nerve paralysis, and altered mental status signify
      advanced disease. The treatment is surgical and recurrences are common. A case of
      cholesteatoma is presented that was associated with extension into the posterior
      fossa and presented with only a headache and localized pain.

PMID- 17499691
TI  - Blunt thyroid trauma with acute hemorrhage and respiratory distress.
AB  - We report a rare event of acute hemorrhage into a thyroid adenoma after blunt
      trauma and causing respiratory distress. A 65-year-old woman fell and hit the
      left side of her anterior neck without any other injuries. The next day, she
      suffered from severe dyspnea and respiratory distress, and visited a community
      hospital. She required endotracheal intubation and was immediately transferred to
      a regional emergency center. Computed tomography and magnetic resonance imaging
      revealed significant tracheal deviation to the right due to an extensive hematoma
      surrounded by a capsule in the left lobe of the thyroid gland with extension to
      the upper mediastinum. The patient was referred to our hospital because the
      diagnosis of malignant thyroid tumor was not completely ruled out. She
      successfully underwent left lobectomy of the thyroid gland without sternotomy.
      The pathological examination revealed follicular adenoma of the thyroid gland
      with massive intratumor bleeding.

PMID- 17499692
TI  - Vaginal bleeding before 20 weeks gestation due to placental abruption leading to
      disseminated intravascular coagulation and fetal loss after appearing to satisfy
      criteria for routine threatened abortion: a case report and brief review of the
      literature.
AB  - We present a case of placental abruption with concomitant disseminated
      intravascular coagulation in a woman who presented with vaginal bleeding. A 32
      year-old pregnant woman at 17 and 4/7 weeks gestation with a 1-month history of
      intermittent abdominal pain presented to our Emergency Department (ED) with 1 h
      of vaginal bleeding. Upon initial history, the patient reported that she was
      diagnosed with "blood behind the placenta" the day before and was discharged on
      pelvic precautions. An ED ultrasound confirmed the sub-amniotic hematoma with
      placental hematoma and a viable intrauterine fetus. A low fibrinogen level was
      suggested for disseminated intravascular coagulation and increasing hemorrhage
      necessitated dilation and evacuation and multiple units of blood products on an
      emergent basis. Only a few cases have been described in the literature
      demonstrating disseminated intravascular coagulation in patients at fewer than 20
      weeks gestation with routine ultrasound findings of live intrauterine pregnancy
      and subchorionic hemorrhage.

PMID- 17499693
TI  - "Crystal dex:" free-base dextromethorphan.
AB  - Dextromethorphan (DXM) is a common component of combination cold medications that
      has become a popular drug of abuse for young adults. Abusers of DXM have
      developed a simple acid-base extraction technique to "free-base," or extract, the
      DXM from the unwanted guaifenesin, coloring agents, sweeteners, and alcohol that
      are typically included in combination cold preparations. We report a case of DXM
      overdose after ingestion of this purified "Crystal Dex" and discuss the "Agent
      Lemon" and single-phase extraction techniques that are used to free-base the
      dextromethorphan.

PMID- 17499694
TI  - Poison centers as information resources for volunteer EMS in a suspected chemical
      exposure.
AB  - In the early part of chemical terrorism or hazardous materials events, protective
      actions and patient care require empirical decisions because reliable and
      accurate information may not be readily available. It has become increasingly
      important to identify reliable information resources that are the most likely to
      be accessed for information during these events. We sought to identify
      information resources that volunteer Emergency Medical Services (EMS) providers
      would use during a suspected chemical exposure. Survey questionnaires were
      completed by 116 of 151 (76.8%) suburban and rural EMS providers. In the past 12
      months, most participants used medical journals and textbooks (59.5%), internet
      sites (57.8%), and poison centers (55.2%) as information resources. For two
      hypothetical scenarios involving chemical exposures, poison centers were most
      frequently chosen as likely contacts for information regarding the identity of
      the agent (case 1: 52.6%, case 2: 48.3%), treatment (74.1%, 64.7%, respectively),
      and antidote (59.5%, 49.1%, respectively). Fire department hazardous materials
      team tied with poison centers as the highest for chemical agent in the second
      scenario (48.3%) and was ranked highest both for decontamination (75.0%, 64.7%,
      respectively) and personal protection (56.9%, 45.7%, respectively). Poison
      centers were selected as the best resource for timely information (70.7%),
      availability (69.0%), and ease of contact (72.4%), and second highest for
      knowledge of chemical agents (44.0%), after CHEMTREC (56.9%). Finally, poison
      centers and CHEMTREC received the highest overall ratings (28.4% and 26.7%,
      respectively). Poison centers are viewed as an important information resource by
      EMS providers and may be the most commonly sought resource for various
      information needs during a suspected chemical exposure.

PMID- 17499695
TI  - The sensitivity and specificity of transcricothyroid ultrasonography to confirm
      endotracheal tube placement in a cadaver model.
AB  - Confirmation of endotracheal (ET) tube placement is critical when performing
      emergency airway management. No single confirmation strategy has emerged as ideal
      in all circumstances. Our objective in this study was to assess the sensitivity
      and specificity of a novel approach to verify endotracheal intubation using
      transcricothyroid ultrasonography (US). We performed a prospective, randomized
      double-blinded trial in a human cadaver model. A 7.5-MHz curvilinear probe was
      placed longitudinally over the cricothyroid membrane as cadavers were randomly
      intubated in either the trachea or esophagus in two phases: 1) as the intubation
      was being performed (dynamic) and, 2) after intubation had been completed
      (static). Volunteer emergency medicine (EM) residents, blinded to tube placement,
      assessed for esophageal vs. tracheal ET placement using dynamic and static US
      views. Sensitivity, specificity, positive predictive value, and negative
      predictive value for detecting esophageal ET placement with 95% confidence
      intervals were calculated. Seven EM residents made a total of 70 dynamic and 70
      static assessments of ET position using transcricothyroid US. Dynamic assessment
      resulted in 97% sensitivity and 100% specificity for detecting esophageal ET
      placement. Static assessment resulted in only 51% sensitivity and 91%
      specificity. This pilot study suggests that dynamic transcricothyroid US is a
      potentially accurate method of confirming ET placement during the intubation
      process. Further investigation in live humans is warranted to validate these
      data.

PMID- 17499696
TI  - Transtracheal 2-d ultrasound for identification of esophageal intubation.
AB  - This prospective, blinded, observational, efficacy study is one of the first to
      evaluate ultrasound in detecting esophageal intubation, a significant source of
      morbidity and mortality. We utilized a convenience sample of patients undergoing
      elective surgery during July 2004 in an urban teaching hospital. Trained
      Emergency Physician sonographers performed transtracheal ultrasounds of
      intubations to identify esophageal intubation. In 35 of the 40 patients enrolled,
      there was intubation of the trachea, whereas esophageal intubation occurred in
      five patients. Sonographers correctly identified all five esophageal intubations,
      for a sensitivity of 100% (95% confidence interval [CI] 48-100). Ultrasound
      correctly identified 34 of 35 tracheal intubations and misidentified one
      resulting in a specificity of 97% (95% CI 90-100). It seems that transtracheal
      ultrasound may be an efficacious adjunct for detecting esophageal intubation.

PMID- 17499697
TI  - Prehospital emergency medical services in Malaysia.
AB  - Once a very slowly developing country in a Southeast Asia region, Malaysia has
      undergone considerable change over the last 20 years after the government changed
      its focus from agriculture to developing more industry and technology. The well
      known "Vision 2020," introduced by the late Prime Minister, set a target for the
      nation to be a developed country in the Asia region by the year 2020. As the
      economy and standard of living have improved, the demand from the public for a
      better health care system, in particular, emergency medical services (EMS), has
      increased. Despite the effort by the government to improve the health care system
      in Malaysia, EMS within the country are currently limited, best described as
      being in the "developing" phase. The Ministry of Health, Ministry of Education,
      Civil Defense, and non-governmental organizations such as Red Crescent and St.
      John's Ambulance, provide the current ambulance services. At the present time,
      there are no uniform medical control or treatment protocols, communication
      systems, system management, training or education, or quality assurance policies.
      However, the recent development of and interest in an Emergency Medicine training
      program has gradually led to improved EMS and prehospital care.

PMID- 17499698
TI  - Utilization of personal digital assistants (PDAS) by pediatric and emergency
      medicine residents.
AB  - The objective of the present study was to investigate the current personal
      digital assistant (PDA) usage patterns of the residents and their interest in
      future PDA-based applications. A cross-sectional survey was conducted among the
      Pediatrics (Peds) and Emergency Medicine (EM) residents in an urban teaching
      hospital. Data points included level of training, specialty of training,
      experience of use of different PDA devices, use of current software applications,
      and interest in future applications. A total of 60/74 (81%) eligible residents
      participated in the study. Palm (Palm Inc., Sunnyvale, CA) was the most commonly
      used operating system (82%). Among the PDA users, 82% reported using the device
      several times a day, and 16% used them a few times a week. The most commonly used
      applications included the simple calculator (81%), drug references (80%), medical
      calculators (75%), electronic textbooks (66%), and schedule and contact
      information (42%). In addition, residents showed interest in using PDA
      applications for procedure logs, patient tracking, and prescription writing. No
      significant differences were noted in the frequency and expertise of using PDAs
      between the Peds and EM residents (p = 0.29). Our data show current trends of use
      of PDAs by Peds and EM residents and their interest for future applications.

PMID- 17499699
TI  - Lens-derived Semaphorin3A regulates sensory innervation of the cornea.
AB  - The cornea, one of the most highly innervated tissues of the body, is innervated
      by trigeminal sensory afferents. During development, axons are initially repelled
      at the corneal margin, resulting in the formation of a circumferential nerve
      ring. The nature and source of guidance molecules that regulate this process
      remain a mystery. Here, we show that the lens, which immediately underlies the
      cornea, repels trigeminal axons in vivo and in vitro. Lens ablation results in
      premature, disorganized corneal innervation and disruption of the nerve ring and
      ventral plexus. We show that Semaphorin3A (Sema3A) is expressed in the lens
      epithelium and its receptor Neuropilin-1 (Npn1) is expressed in the trigeminal
      ganglion during cornea development. Inhibition of Sema3A signaling abrogates axon
      repulsion by the lens and cornea in vitro and phenocopies lens removal in vivo.
      These results demonstrate that lens-derived Sema3A mediates initial repulsion of
      trigeminal sensory axons from the cornea and is necessary for the proper
      formation of the nerve ring and positioning of the ventral plexus in the choroid
      fissure.

PMID- 17499700
TI  - Characterization of a sperm factor for egg activation at fertilization of the
      newt Cynops pyrrhogaster.
AB  - Eggs of the newt, Cynops pyrrhogaster, arrested at the second meiotic metaphase
      are activated by sperm at fertilization and then complete meiosis to initiate
      development. We highly purified a sperm factor for egg activation from a sperm
      extract with several chromatographies. The purified fraction containing only a 45
      kDa protein induced egg activation accompanied by an intracellular Ca2+ increase
      when injected into unfertilized eggs. Although injection of mouse phospholipase C
      (PLC) zeta-mRNA caused a Ca2+ increase and egg activation, partial amino acid
      sequences of the 45 kDa protein were homologous to those of Xenopus citrate
      synthase, but not to PLCs. An anti-porcine citrate synthase antibody recognized
      the 45 kDa protein both in the purified fraction and in the sperm extract.
      Treatment with the anti-citrate synthase antibody reduced the egg-activation
      activity in the sperm extract. Injection of porcine citrate synthase or mRNA of
      Xenopus citrate synthase induced a Ca2+ increase and caused egg activation. A
      large amount of the 45 kDa protein was localized in two lines elongated from the
      neck to the middle piece of sperm. These results indicate that the 45 kDa protein
      is a major component of the sperm factor for egg activation at newt
      fertilization.

PMID- 17499701
TI  - Regulatory roles of nitric oxide during larval development and metamorphosis in
      Ciona intestinalis.
AB  - Metamorphosis in the ascidian Ciona intestinalis is a very complex process which
      converts a swimming tadpole to an adult. The process involves reorganisation of
      the body plan and a remarkable regression of the tail, which is controlled by
      caspase-dependent apoptosis. However, the endogenous signals triggering apoptosis
      and metamorphosis are little explored. Herein, we report evidence that nitric
      oxide (NO) regulates tail regression in a dose-dependent manner, acting on
      caspase-dependent apoptosis. An increase or decrease of NO levels resulted in a
      delay or acceleration of tail resorption, without affecting subsequent juvenile
      development. A similar hastening effect was induced by suppression of cGMP
      dependent NO signalling. Inhibition of NO production resulted in an increase in
      caspase-3-like activity with respect to untreated larvae. Detection of
      endogenously activated caspase-3 and NO revealed the existence of a spatial
      correlation between the diminution of the NO signal and caspase-3 activation
      during the last phases of tail regression. Real-time PCR during development, from
      early larva to early juveniles, showed that during all stages examined, NO
      synthase (NOS) is always more expressed than arginase and it reaches the maximum
      value at late larva, the stage immediately preceding tail resorption. The spatial
      expression pattern of NOS is very dynamic, moving rapidly along the body in very
      few hours, from the anterior part of the trunk to central nervous system (CNS),
      tail and new forming juvenile digestive organs. NO detection revealed free
      diffusion from the production sites to other cellular districts. Overall, the
      results of this study provide a new important link between NO signalling and
      apoptosis during metamorphosis in C. intestinalis and hint at novel roles for the
      NO signalling system in other developmental and metamorphosis-related events
      preceding and following tail resorption.

PMID- 17499702
TI  - Cooperation between the PDGF receptors in cardiac neural crest cell migration.
AB  - Neural crest cells (NCCs) are essential components of the sympathetic nervous
      system, skin, craniofacial skeleton, and aortic arch. It has been known for many
      years that perturbation of migration, proliferation, and/or differentiation of
      these cells leads to birth defects such as cleft palate and persistent truncus
      arteriosus (PTA). Previously, we had shown that disruption of the platelet
      derived growth factor receptor (PDGFR) alpha in NCCs resulted in defects in
      craniofacial and aortic arch development, the latter with variable penetrance.
      Because we observed ventricular septal defects in embryos that are null for the
      PDGFRbeta, we hypothesized that both PDGF receptors are involved in NCC
      formation. Here, we show that both receptors are expressed in cardiac NCCs and
      that the combined loss of the PDGFRalpha and PDGFRbeta in NCCs resulted in NCC
      related heart abnormalities, including PTA and a ventricular septal defect (VSD).
      Using NCC lineage tracing, we observed that loss of PDGF receptor signaling
      resulted in reduced NCCs in the conotruncus region, leading to defects in aortic
      arch septation. These results indicate that while PDGFRalpha plays a predominant
      role in NCC development, the PDGFRbeta is expressed by and functions in cardiac
      NCCs. Combined PDGF receptor signaling is required for sufficient recruitment of
      cardiac NCCs into the conotruncal region and for formation of the aortico
      pulmonary and ventricular septum.

PMID- 17499704
TI  - The Hopkins Lupus Pregnancy Center: ten key issues in management.
AB  - There is no consensus on the management of systemic lupus erythematosus (SLE),
      much less pregnancy in SLE patients. However, several key issues in the
      management of SLE in pregnancy are commonly faced by rheumatologists,
      nephrologists, and obstetricians. These include the treatment of SLE activity in
      pregnancy, the ascertainment of lupus nephritis, treatment of antiphospholipid
      antibodies, treatment of hypertension, and laboratory monitoring. These key
      issues will be examined in this chapter.

PMID- 17499706
TI  - Management of the high-risk lupus pregnant patient.
AB  - Pregnancy in the lupus patient presents a unique clinical challenge. Pregnancy
      may interact with lupus nephritis and adds preeclampsia to the differential
      diagnosis of hypertension. Lupus may result in pregnancy loss, fetal growth
      restriction, and prematurity. The obstetric management of these complex issues is
      presented for the nonobstetrician.

PMID- 17499705
TI  - Lupus activity in pregnancy.
AB  - Pregnancy in a woman with systemic lupus erythematosus (SLE) can be complicated
      by both lupus activity and pregnancy mishaps. The majority of recent studies
      found an increase in lupus activity during pregnancy, perhaps exacerbated by
      hormonal shifts required to maintain pregnancy. Increased lupus activity, in
      turn, prompts an elevated risk for poor pregnancy outcomes, including stillbirth,
      preterm birth, low birth weight, and preeclamspsia. Fortunately, the majority of
      pregnancies in women with SLE are successful. However, the interaction between
      pregnancy and SLE activity can lead to complications for both mother and baby.

PMID- 17499707
TI  - Neonatal lupus syndromes.
AB  - Neonatal lupus has become an important model of passively acquired autoimmunity
      since the seminal observation in the late 1970s that sera from nearly all mothers
      of children with isolated congenital heart block (CHB) contain specific
      autoantibodies.

PMID- 17499708
TI  - Antiphospholipid syndrome in pregnancy.
AB  - Antiphospholipid syndrome (APS) is frequently associated with complications
      during pregnancy. Miscarriage and maternal thrombosis are the most common
      problems, but prematurity, intrauterine growth retardation, pregnancy-induced
      hypertensive disorders, and pulmonary hypertension can complicate pregnancy as
      well. The correct treatment of these women requires an accurate preconceptual
      counseling and a close collaboration between obstetricians and physicians.
      Doppler studies of the umbilical and uterine arteries play an important role in
      predicting APS-related complications during pregnancy.

PMID- 17499709
TI  - Pregnancy and vasculitis.
AB  - Until recently, the prognosis associated with many forms of systemic vasculitis
      was quite grim. Advances in this field have allowed us to begin to focus on
      issues related to quality of life such as fertility, conception, and pregnancy
      among women with vasculitis. Because the systemic vasculitides are rare
      diagnoses, many important questions remain unanswered. Overall, it seems that
      women who have inactive vasculitis may not be subject to unusual complications
      during pregnancy, but our understanding of the interaction between pregnancy and
      specific forms of vasculitis continues to evolve.

PMID- 17499710
TI  - Rheumatoid arthritis and reproduction.
AB  - Additional research is needed to establish the safety of biologic agents in
      pregnancy and lactation. The practitioner should convey information regarding the
      natural history of rheumatoid arthritis during pregnancy and safety issues
      related to pharmacotherapies to every woman of childbearing age with RA, well
      before conception and pregnancy, to ensure optimal outcomes.

PMID- 17499711
TI  - Pregnancy in scleroderma.
AB  - Pregnancy in systemic sclerosis may be uneventful with good maternal and fetal
      outcomes. Scleroderma is a multisystem disease and complications do occur;
      however, careful antenatal evaluations, discussion of potential problems, and
      participation in a high-risk obstetric monitoring program are important to
      optimize the best outcome. Women who have diffuse scleroderma are at a greater
      risk for developing serious cardiopulmonary and renal problems early in the
      disease so they should be encouraged to delay pregnancy until the disease
      stabilizes. All patients who become pregnant during this high-risk time should be
      monitored extremely carefully, particularly for renal crisis.

PMID- 17499712
TI  - Lanthanum suppresses arachidonic acid-induced cell death and mitochondrial
      depolarization in PC12 cells.
AB  - Within the framework of studying the mechanisms of acute toxicity of arachidonic
      acid and the role of ambient cations, we have investigated the effects of
      extracellular La(3+) on arachidonic acid-induced death (lactate dehydrogenase
      release) and mitochondrial depolarization (rhodamine 123 fluorescence) in PC12
      cells. Micromolar La(3+) profoundly suppressed arachidonic acid toxicity and this
      effect was dependent on the presence of other cations. Whereas in the cation-free
      solution 10-20 microM La(3+) protected most cells from death caused by a 2 hour
      long exposure to 20 microM arachidonic acid, the cytoprotective effect of 100
      microM La(3+) was reduced to approximately 70% in the presence of a normal
      complement of monovalent cations and was hardly detectable with 5 mM Ca(2+) in
      the bath. Increasing the concentration of arachidonic acid could defeat La(3+)
      cytoprotection. In fluorescence experiments, arachidonic acid caused a decrease
      in the mitochondrial membrane potential, with the rate and extent of
      depolarization increasing with an increase in the concentration of arachidonic
      acid. La(3+) countered the depolarizing effect of arachidonic acid in a manner
      consistent with a decrease in the effective arachidonic acid concentration. The
      results suggest that extracellular cations modulate cellular effects of
      arachidonic acid by reducing its ability to pass through the plasma membrane,
      possibly by binding the fatty acid. The similarities of the La(3+) effects on
      arachidonic acid-induced cell death and arachidonic acid-induced mitochondrial
      depolarization strongly support the causal relations between the two events and
      suggest that mitochondria are the primary target of arachidonic acid at the
      cellular level.

PMID- 17499713
TI  - Cyclohexenonic long-chain fatty alcohol has therapeutic effects on diabetes
      induced angiopathy in the rat aorta.
AB  - We studied the effects of cyclohexenonic long-chain fatty alcohol (N-hexacosanol)
      on diabetes-induced angiopathy in the rat aorta. Male Sprague-Dawley rats were
      divided into 4 groups, a control group and 3 other groups in which diabetes was
      induced by streptozotocin (50 mg/kg i.p.). Four weeks after the induction of
      diabetes, the 3 groups received treatment with either vehicle or N-hexacosanol (2
      or 8 mg/kg, i.p. every day) for another 4 weeks. To determine the mechanisms of
      diabetic vascular dysfunction and the effects of N-hexacosanol, we conducted
      organ bath studies and real-time polymerase chain reaction on muscarinic M(3)
      receptor, and endothelial and inducible nitric oxide synthase (eNOS and iNOS)
      mRNAs in the rat aorta. Treatment with N-hexacosanol did not alter the diabetic
      status, but improved the diabetes-induced hypercontraction produced by
      norepinephrine and the damaged endothelium-dependent relaxation of the rat aorta
      induced by acetylcholine. Furthermore, in the diabetic rats, both muscarinic M(3)
      receptor and iNOS mRNAs were significantly increased, and N-hexacosanol reversed
      these upregulations. However, the expression of eNOS mRNA showed no change in all
      groups. These results indicate that N-hexacosanol has beneficial effects on
      functional dysfunction and reverses the upregulation of muscarinic M(3) receptor
      and iNOS mRNAs in the diabetic rat aorta.

PMID- 17499714
TI  - Mitochondria, ciglitazone and liver: a neglected interaction in biochemical
      pharmacology.
AB  - Peroxisome proliferator activated receptors (PPARs) are a class of nuclear
      receptors now actively investigated for their involvement in lipid and glucidic
      metabolism, immune regulation and cell differentiation. Drugs binding and
      activating PPARs are therefore attracting attention for their potential
      therapeutic role in various diseases like type 2 diabetes, dyslipidemias,
      atherosclerosis, obesity (i.e., metabolic syndrome). Agonists of these receptors
      have been already used in therapeutic protocols: fibrates (PPAR-alpha ligands)
      are being used in hyperlipidemias, and thiazolidinediones (mainly PPAR-gamma
      ligands) are being employed as insulin sensitizers. The latter drugs introduction
      into therapy, however, showed very soon some unwanted effects (hepatotoxicity at
      first and myocardiotoxicity later on) which confirmed some contradictory data
      already suggested by pre-clinical trial-experiments. In this study we show that
      some PPAR ligands impair mitochondrial oxidative metabolism in human liver cell
      line mainly by deranging NADH oxidation. Intriguingly, the PPAR-gamma ligand
      ciglitazone caused a dose-dependent inhibition of NADH-cytochrome c reductase
      that resulted, at a drug concentration of 50 microM, of about 60% (P<0.001),
      while other PPAR ligands with different receptor affinity - positive controls
      like clofibrate (0.7 mM), gemfibrozil (0.23 mM) and bezafibrate (1 mM) - reduced
      the activity of mitochondrial Complex I by about 20% (P<0.01, P<0.01 and P<0.05,
      respectively). The induced mitochondrial dysfunction imposed a series of
      metabolic compensatory adaptations characterized by a significant shift to
      anaerobic glycolysis. These findings underline the undervalued non-genomic
      effects of PPAR ligands and can provide a better understanding of the
      pharmacotoxicological profiles of these drugs and of their roles in the therapy
      of diabetes mellitus.

PMID- 17499715
TI  - Structural analysis of vimentin and keratin intermediate filaments by cryo
      electron tomography.
AB  - Intermediate filaments are a large and structurally diverse group of cellular
      filaments that are classified into five different groups. They are referred to as
      intermediate filaments (IFs) because they are intermediate in diameter between
      the two other cytoskeletal filament systems that is filamentous actin and
      microtubules. The basic building block of IFs is a predominantly alpha-helical
      rod with variable length globular N- and C-terminal domains. On the ultra
      structural level there are two major differences between IFs and microtubules or
      actin filaments: IFs are non-polar, and they do not exhibit large globular
      domains. IF molecules associate via a coiled-coil interaction into dimers and
      higher oligomers. Structural investigations into the molecular building plan of
      IFs have been performed with a variety of biophysical and imaging methods such as
      negative staining and metal-shadowing electron microscopy (EM), mass
      determination by scanning transmission EM, X-ray crystallography on fragments of
      the IF stalk and low-angle X-ray scattering. The actual packing of IF dimers into
      a long filament varies between the different families. Typically the dimers form
      so called protofibrils that further assemble into a filament. Here we introduce
      new cryo-imaging methods for structural investigations of IFs in vitro and in
      vivo, i.e., cryo-electron microscopy and cryo-electron tomography, as well as
      associated techniques such as the preparation and handling of vitrified sections
      of cellular specimens.

PMID- 17499716
TI  - Alternative cyclin D1 forms a and b have different biological functions in the
      cell cycle of B lymphocytes.
AB  - Cyclin D1 is an important regulator of the early phase of the cell cycle and the
      transcriptional machinery. It is often deregulated in human tumors of various
      origins and is considered to be an oncogene. The CCND1 gene encoding cyclin D1
      generates two mRNAs by alternative splicing, leading to the production of two
      alternative proteins: a long form a (36 kDa) and a short form b (30-31 kDa) from
      which the C-terminal moiety required for protein stability and sub-cellular
      localization has been deleted. Both forms of RNA and protein have been detected
      in B-cell hemopathies, but their respective roles are unclear. We investigated
      the function of cyclin D1b in cell cycle regulation, by generating B-cell lines
      displaying conditional expression of isoform b. Comparisons of these cell lines
      (BD1b series) with previously obtained cell lines expressing cyclin D1a
      demonstrated that cyclin D1b had no cell cycle regulatory properties.

PMID- 17499717
TI  - Rpn13p and Rpn14p are involved in the recognition of ubiquitinated Gcn4p by the
      26S proteasome.
AB  - The 26S proteasome, composed of the 20S core and 19S regulatory complexes, is
      important for the turnover of polyubiquitinated proteins. Each subunit of the
      complex plays a special role in proteolytic function, including substrate
      recruitment, deubiquitination, and structural contribution. To assess the
      function of some non-essential subunits in the 26S proteasome, we isolated the
      26S proteasome from deletion strains of RPN13 and RPN14 using TAP affinity
      purification. The stability of Gcn4p and the accumulation of ubiquitinated Gcn4p
      were significantly increased, but the affinity in the recognition of proteasome
      was decreased. In addition, the subcomplexes of the isolated 26S proteasomes from
      deletion mutants were less stable than that of the wild type. Taken together, our
      findings indicate that Rpn13p and Rpn14p are involved in the efficient
      recognition of 26S proteasome for the proteolysis of ubiquitinated Gcn4p.

PMID- 17499718
TI  - An efficient chemoenzymatic production of small molecule glucosides with in situ
      UDP-glucose recycling.
AB  - A one-pot system for efficient enzymatic synthesis of curcumin glucosides is
      described. The method couples the activities of two recombinant enzymes, UDP
      glucose: curcumin glucosyltransferase from Catharanthus roseus (CaUGT2) and
      sucrose synthase from Arabidopsis thaliana (AtSUS1). UDP, a product inhibitor of
      UDP-glucosyltransferase, was removed from the system and used for regeneration of
      UDP-glucose by the second enzyme, AtSUS1. The productivity was increased several
      fold and UDP-glucose initially added to the reaction mixture could be reduced to
      one-tenth of the normal level. The concept of enhancing glucosylation efficiency
      by coupling a UDP-glucose regeneration system with glucosyltransferases should be
      applicable to enzymatic production of a wide range of glucosides.

PMID- 17499719
TI  - Structural basis of diversification of fungal retinal proteins probed by site
      directed mutagenesis of Leptosphaeria rhodopsin.
AB  - Numerous fungal genomes encode homologs of bacteriorhodopsin (BR), but only two
      fungal rhodopsins were overexpressed and characterized spectroscopically.
      Neurospora rhodopsin (NR) is a slow-cycling sensory rhodopsin-like protein, while
      Leptosphaeria rhodopsin (LR) is a BR-like proton pump. Recently, we found that a
      conservative replacement of the cytoplasmic proton donor Asp150 by Glu converts
      LR into an NR-like protein. In this work, we search for structural reasons for
      the dramatic differences in their photochemistry by mutating the hydrogen-bonding
      partner of Asp150 (Thr87) and three additional residues (Thr233, Asp248, and
      Gly271) selected by comparison of the primary structures of NR and LR. We
      conclude that while these residues may contribute to the differences between LR
      and NR, they are not crucial for the optimization of the Schiff base
      reprotonation by Asp150, and that the dramatic effect of the D150E mutation is
      not a simple result of the introduction of a bulkier glutamate sidechain.

PMID- 17499720
TI  - Camellia oil and its distillate fractions effectively inhibit the spontaneous
      metastasis of mouse melanoma BL6 cells.
AB  - We previously reported that daily intraperitoneal injections of oleamide weakly
      inhibits the spontaneous metastasis of BL6 cells by blocking the gap junction
      mediated intercellular communications (GJIC) of connexin 26 (Cx26). In the
      present study, we tested camellia oil, olive oil and cottonseed oil which are
      rich in oleamide-like oleic acid for their inhibitory potency on Cx26-mediated
      GJIC and spontaneous metastasis of BL6 cells. We found that camellia oil, olive
      oil and cottonseed oil, and their distillate fractions inhibited Cx26-mediated
      GJIC. We also showed that daily intraperitoneal injection of camellia oil and its
      distillate fractions more potently inhibited spontaneous lung metastasis of BL6
      cells than oleamide. Moreover, a daily oral administration of camellia oil
      distillate fraction effectively inhibited spontaneous metastasis. Notably, even
      camellia Tempura-oil, a commercially available food, weakly inhibited the
      spontaneous metastasis of BL6 cells. Since these oils are used as foods and are
      quite safe, we propose that they could be used as supplements to protect patients
      from lung metastasis of melanomas.

PMID- 17499721
TI  - c-Myc is required for transformation of FDC-P1 cells by EGFRvIII.
AB  - In contrast to wtEGFR, its truncated version EGFRvIII transformed non-tumorigenic
      FDC-P1 cells only when c-Myc was coexpressed. In nude mice, EGFRvIII/c-Myc
      coexpressing cells induced tumors, whereas wtEGFR-expressing EGF-dependent FDC-P1
      cells did not. EGFRvIII function was required for both the induction and
      maintenance of tumor growth. Cellular proliferation was inhibited by a selective
      EGFR tyrosine kinase inhibitor indicating intrinsic tyrosine kinase activities
      for both receptors. Unlike wtEGFR, constitutive signaling by EGFRvIII was
      refractory to stimulation by the EGFR ligands EGF and TGF-alpha. Summarized,
      EGFRvIII is a constitutively active receptor tyrosine kinase whose transforming
      capacity is lower than that of EGF-stimulated wtEGFR.

PMID- 17499722
TI  - ClpP: a distinctive family of cylindrical energy-dependent serine proteases.
AB  - Processes maintaining protein homeostasis in the cell are governed by the
      activities of molecular chaperones that mainly assist in the folding of
      polypeptide chains and by a large class of proteases that regulate protein levels
      through degradation. ClpP proteases define a distinctive family of cylindrical,
      energy-dependent serine proteases that are highly conserved throughout bacteria
      and eukaryota. They typically interact with ATP-dependent AAA+ chaperones that
      bind and unfold target substrates and then translocate them into ClpP for
      degradation. Structural and functional studies have provided a detailed view of
      the mechanism of function of this class of proteases.

PMID- 17499723
TI  - One-step high-radiochemical-yield synthesis of [18F]FP-CIT using a protic solvent
      system.
AB  - Although [18F] fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) is a
      promising radiopharmaceutical for dopamine transporter imaging, it has not been
      used for clinical studies because of low radiochemical yield. The purpose of our
      study was to develop a new radiochemistry method using a protic solvent system to
      obtain a high radiochemical yield of [18F]FP-CIT in single-step manual and
      automatic preparation procedures. [18F]F(-) was trapped on a QMA Sep-Pak
      cartridge or PS-HCO(3) cartridge and eluted with Cs2CO(3)/K222 buffer or TBAHCO3
      respectively, or 8 microl of TBAOH was added directly to [18F]F(-)/H(2)(18)O
      solution in a reactor without using a cartridge. After drying, 18F] fluorination
      was performed with 2-6 mg of mesylate precursor, 100 microl of CH(3)CN and 500
      microl of t-BuOH at 50-120 degrees C for 5-30 min, followed by high-performance
      liquid chromatography (HPLC) purification to obtain the final product. For
      comparison, the same procedure was performed with a tosylate precursor. Manual
      synthesis gave a decay-corrected radiochemical yield of 52.2+/-4.5%, and optimal
      synthesis conditions were as follows: TBAOH addition, 4 mg of precursor, 100
      degrees C and 20 min of [18F] fluorination (n=3). We obtained low radiochemical
      yields of [18F]FP-CIT with carbonate elution systems such as Cs2CO(3) or TBAHCO3.
      We also developed an automatic synthesis method based on manual synthesis
      results. In automatic production, we obtained a decay-corrected radiochemical
      yield of 35.8+/-5.2% after HPLC purification, and we did not have any synthesis
      failures (n=14). Here, we describe our new method for the synthesis of [18F]FP
      CIT using a protic solvent system. This method gave a high radiochemical yield
      with high reproducibility and might enable [18F]FP-CIT to be used clinically and
      commercially.

PMID- 17499725
TI  - Radiolabeled high affinity peptidomimetic antagonist selectively targets
      alpha(v)beta(3) receptor-positive tumor in mice.
AB  - OBJECTIVES: The aim of this research was to synthesize radiolabeled
      peptidomimetic integrin alpha(v)beta(3) antagonists that selectively target
      integrin alpha(v)beta(3) receptor and clear rapidly from the whole body. METHODS:
      Integrin alpha(v)beta(3) antagonists, 4-[2-(3,4,5,6-tetrahydropyrimidine-2
      ylamino)ethyloxy]benzoyl-2-(S)-aminoethylsulfonyl-amino-beta-alanine (IA) and 4
      [2-(3,4,5,6-tetrahydro-pyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino
      neopenta-1-carbamyl)]-aminoethylsulfonylamino-beta-alanine hydrochloride (IAC), a
      hydrophobic carbamate derivative of IA, were conjugated with 2-p
      isothiocyanatobenzyl-DOTA at the amino terminus and labeled with (111)In. The
      (111)In labeled IA and IAC were subjected to in vitro receptor binding,
      biodistribution and imaging studies using nude mice bearing the receptor-positive
      M21 human melanoma xenografts. RESULTS: The (111)In-labeled IA (40%) and -IAC
      (72%) specifically bound in vitro to alpha(v)beta(3) (0.8 microM) at a molar
      excess. This receptor binding was completely blocked by a molar excess of cold IA
      to alpha(v)beta(3). The higher receptor-binding affinity of the (111)In-labeled
      IAC was reflected in higher tumor uptake and retention: 5.6+/-1.4 and 4.5+/-0.7
      %ID/g vs. 3.8+/-0.9 and 2.0+/-0.3 %ID/g for the (111)In-labeled IA at 0.33 and 2
      h. The tumor uptakes were inhibited by the co-injection of 200 microg of IA,
      indicating that the uptake was receptor mediated. These antagonists were excreted
      primarily via the renal system. The (111)In activity retained in the whole body
      was quite comparable between the (111)In-labeled IA (24% ID) and the (111)In
      labeled IAC (33% ID) at 2 h. The higher peak tumor uptake and longer retention
      resulted in higher tumor-to-background ratios for the (111)In-labeled IAC at 2 h
      with 9.7, 2.3, 0.8, 1.9, 7.1, 2.2, 0.9, 3.7 and 9.9 for blood, liver, kidney,
      lung, heart, stomach, intestine, bone and muscle, respectively. The imaging
      studies with the (111)In-labeled IAC also clearly visualized the receptor
      positive tumor at 4 h. CONCLUSIONS: The (111)In-labeled IAC showed an improve
      tumor targeting kinetics with rapid accumulation and prolonged retention in the
      alpha(v)beta(3) receptor-positive tumor. This together with the rapid whole-body
      clearance pharmacokinetics warrants further studies on this IAC analog for
      molecular imaging of tumor-induced angiogenic vessels and various malignant human
      tumors expressing the receptor.

PMID- 17499724
TI  - PET Imaging of CRF1 with [11C]R121920 and [11C]DMP696: is the target of
      sufficient density?
AB  - AIM: Overstimulation of the CRF type 1 receptor (CRF1) is implicated in anxiety
      and depressive disorders. The aim of this study was to investigate the in vivo
      binding characteristics of [11C]R121920 and [11C]DMP696 in the nonhuman primate
      for application in positron emission tomography (PET) studies of CRF1. METHODS:
      PET imaging with the two novel CRF1 radioligands was performed in baboon. In
      vitro binding studies for CRF1 were performed in postmortem brain tissue of
      baboon and human to assess sufficiency of receptor density for PET. RESULTS: Both
      [11C]R121920 and [11C]DMP696 distributed rapidly and uniformly throughout the
      brain. Washout was comparable across brain regions, without differences in volume
      of distribution between regions reported to have high and low in vitro CRF1
      binding. Membrane-enriched tissue homogenate assay using [(125)I]Tyr(0)-sauvagine
      and specific CRF1 antagonists CP154,526 and SN003 in human occipital cortex
      yielded maximal binding (Bmax) of 63.3 and 147.3 fmol/mg protein, respectively,
      and in human cerebellar cortex yielded Bmax of 103.6 and 64.6 fmol/mg protein,
      respectively. Dissociation constants (K(D)) were subnanomolar. In baboon,
      specific binding was not detectable in the same regions; therefore, Bmax and K(D)
      were not measurable. Autoradiographic results were consistent except there was
      also detectable CRF1-specific binding in baboon cerebellum. CONCLUSION: Neither
      [11C]R121920 nor [11C]DMP696 demonstrated quantifiable regional binding in vivo
      in baboon. In vitro results suggest CRF1 density in baboon may be insufficient
      for PET. Studies in man may generate more promising results due to the higher
      CRF1 density compared with baboon in cerebral cortex and cerebellum.

PMID- 17499726
TI  - Differences in binding of (99m)Tc-disintegrins to integrin alphavbeta3 on tumor
      and vascular cells.
AB  - Disintegrins, which contain an Arg-Gly-Asp sequence in their binding domains are
      antagonists of integrins such as alphavbeta3. The purpose of this study was to
      compare a range of disintegrins with different integrin selectivities for their
      binding behavior in vitro to vascular endothelial cells bearing alphavbeta3 and
      to cultured tumor cells which express alphavbeta3. METHODS: Five disintegrins
      (bitistatin, kistrin, flavoridin, VLO4 and echistatin) and a cyclic pentapeptide,
      c[RGDyK], were radiolabeled with (99m)Tc and tested for binding to cells in
      vitro. RESULTS: (99m)Tc-Kistrin, flavoridin and VLO4 had the highest binding,
      (99m)Tc-echistatin had moderate binding, and (99m)Tc-bitistatin and (99m)Tc
      c[RGDyK] had low binding to cells. The observed binding was attributed to
      alphavbeta3 to various extents: echistatin, bitistatin>kistrin>flavoridin>VLO4.
      Cancer cells internalized bound disintegrins after binding, but endothelial cells
      did not. After binding to endothelial cells, (99m)Tc-kistrin was not displaced by
      competing peptide or plasma proteins. CONCLUSIONS: These data suggest that
      radiolabeled kistrin, flavoridin and VLO4 may have advantages over labeled
      bitistatin and small cyclic peptides for targeting alphavbeta3 in vivo. Since
      receptor-bound radioligand is not internalized by endothelial cells, disintegrins
      may provide an advantage for targeting alphavbeta3 on vasculature because they
      bind strongly to surface receptors and are not readily displaced.

PMID- 17499727
TI  - Synthesis and biodistribution of fluorine-18-labeled fluorocyclofenils for
      imaging the estrogen receptor.
AB  - C4-[18F]Fluorocyclofenil ([18F]FCF, 6) and C3-[18F]fluoroethylcyclofenil
      ([18F]FECF, 9), two high-affinity nonsteroidal estrogens, were prepared and
      investigated as potential agents for imaging estrogen receptors (ERs) in breast
      tumors. Both of these compounds could be prepared conveniently from alkyl
      methanesulfonate precursors (5,8) by fluoride displacement reactions, and they
      were obtained in high radiochemical purity and radiochemical yields, with
      effective specific activities sufficient for in vivo biodistribution studies.
      While the biodistribution of [18F]FCF (6) in immature female rats showed no
      selective target tissue uptake, the biodistribution of [18F]FECF (9) showed
      selective uptake by the uterus, but this uptake could not be blocked by excess
      estradiol. The poor in vivo biodistribution of these otherwise high-affinity
      ligands arouses curiosity, and together with recent results on the
      biodistribution of other nonsteroidal ligands suggests that factors other than
      receptor binding affinity are important for in vivo imaging of estrogen target
      tissues and ER-positive breast tumors.

PMID- 17499728
TI  - Pre vivo, ex vivo and in vivo evaluations of [68Ga]-EDTMP.
AB  - INTRODUCTION: The objectives of this study were to develop a simple preparation
      method for [68Ga]-EDTMP and to evaluate the applicability of [68Ga]-EDTMP as a
      potential positron emission tomography (PET) bone imaging agent using pre vivo,
      ex vivo and in vivo models. METHODS: [68Ga]-EDTMP was prepared using 68Ga]
      gallium chloride eluted from the 68Ge/68Ga generator and commercially available
      Multibone kits. Binding affinity to bone compartments was evaluated using a
      recently established pre vivo model. In vivo (microPET) and ex vivo experiments
      were performed in mice, and the results of which were compared with those
      obtained with [18F]-fluoride. RESULTS: [68Ga]-EDTMP was accessible via simple kit
      preparation and predominantly accumulated in bone tissue in vivo, ex vivo and pre
      vivo. Binding to mineral bone was irreversible, and low binding was observed in
      organic bone. In vivo microPET evaluation revealed predominant uptake in bone
      with renal excretion. Compared with [18F]-fluoride, the uptake was lower and the
      PET image quality was reduced. CONCLUSIONS: From the present evaluation, apart
      from the autonomy for PET centers without an onsite cyclotron, the advantage of
      [68Ga]-EDTMP over [18F]-fluoride is not apparent and the future clinical prospect
      of [68Ga]-EDTMP remains speculative.

PMID- 17499729
TI  - Radiolabeling small RNA with technetium-99m for visualizing cellular delivery and
      mouse biodistribution.
AB  - To develop a noninvasive direct method for the in vivo tracking of small
      interfering RNA (siRNA) used in RNA interference, two 18-nucleotide
      oligoribonucleotides were radiolabeled with technetium-99m ((99m)Tc-RNA). The
      ability of (99m)Tc-RNA to track delivery was tested in cultured cells and living
      mice. The cellular delivery of (99m)Tc-RNAs could be quantified by gamma counting
      and could be visualized by microautoradiography. Radiolabeled RNAs can be
      efficiently delivered into cells by reaching up to 3x10(5) molecules of small
      RNAs per cell. Moreover, RNAs were internalized with homogeneous distribution
      throughout the cytoplasm and nucleus. In tumor-bearing mice, whole-body images
      and biodistribution studies showed that (99m)Tc-RNAs were delivered to almost all
      tissues after intravenous injection. The imaging of living animals allowed
      noninvasive and longitudinal monitoring of the in vivo delivery of these small
      RNAs. In conclusion, using (99m)Tc radiolabeling, the delivery of small RNAs
      could be measured quantitatively in cultured cells and could be noninvasively
      visualized in living animals using a gamma camera. The results of this study
      could open up a new approach for measuring the in vivo delivery of small RNAs
      that might further facilitate the development of siRNAs as targeted therapies.

PMID- 17499730
TI  - Tumor resection cavity administered iodine-131-labeled antitenascin 81C6
      radioimmunotherapy in patients with malignant glioma: neuropathology aspects.
AB  - INTRODUCTION: The neurohistological findings in patients treated with targeted
      beta emitters such as (131)I are poorly described. We report a histopathologic
      analysis from patients treated with combined external beam therapy and a
      brachytherapy consisting of a (131)I-labeled monoclonal antibody (mAb) injected
      into surgically created resection cavities during brain tumor resections.
      METHODS: Directed tissue samples of the cavity walls were obtained because of
      suspected tumor recurrence from 28 patients. Samples and clinical follow-up were
      evaluated on all patients (Group A) based on total radiation dose received and a
      subset of these (n=18; Group B, proximal therapy subset) who had received
      external beam therapy within <or=3 months of mAb therapy and undergoing 26
      biopsies over 37 months. Histologic outcomes were "proliferative glioma,"
      "quiescent glioma" and negative for neoplasm. Statistical analysis was used to
      assess the casual relation between total absorbed dose ((131)I-mAb+external beam)
      and histologic diagnosis. RESULTS: The lesions observed after (131)I-mAb therapy
      were qualitatively similar to those reported for other types of radiation
      therapy; however, the high localized dose rate and absorbed doses produced by the
      short range of (131)I beta particles seem to have resulted in an earlier necrotic
      reaction in the tumor bed. Among all 28 (Group A) patients, median survival from
      tissue analysis after mAb therapy depended on histopathology and total radiation
      absorbed dose. Median survival for patients with tissue classified as
      proliferative glioma, quiescent glioma and negative for neoplasm were 3.5, 15 and
      27.5 months, respectively. Without categorization, total dose was a significant
      predictor of survival (P<.002) where patients with higher doses had better
      prognoses. For example, median survival in patients receiving a total radiation
      dose greater than 86 Gy was 19 months compared with 7 months for those receiving
      less than 86 Gy. CONCLUSIONS: Histopathologic analysis correlated with prognosis.
      Among all patients (Group A) there was a significant correlation between biopsy
      outcome, survival, and total radiation absorbed dose. Among the Group B proximal
      therapy patients, the neuropathologic changes were qualitatively similar to those
      described for external beam therapy and interstitial brachytherapy.

PMID- 17499731
TI  - Biodistribution, pharmacokinetics and imaging of (188)Re-BMEDA-labeled pegylated
      liposomes after intraperitoneal injection in a C26 colon carcinoma ascites mouse
      model.
AB  - Nanoliposomes are important carriers capable of packaging drugs for various
      delivery applications through passive targeting tumor sites by enhanced
      permeability and retention effect. Radiolabeled liposomes have potential
      applications in radiotherapy and diagnostic imaging. The purpose of this study
      was to investigate the biodistribution, pharmacokinetics and imaging of
      nanotargeted (188)Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine
      (BMEDA)-labeled pegylated liposomes (RBLPL) and unencapsulated (188)Re-BMEDA
      after intraperitoneal (ip) injection in a C26 colon carcinoma ascites mouse
      model. The nanopegylated liposomes were labeled with (188)Re-BMEDA. The labeling
      efficiency of RBLPL was 82.3+/-4.5%. In vitro stability of RBLPL in normal saline
      at room temperature and in rat plasma at 37 degrees C for 72 h was 92.01+/-1.31%
      and 82.4+/-1.64%, respectively. The biodistribution studies indicated that the
      radioactivity in ascites was 69.96+/-14.08 percentage injected dose per gram (%
      ID/g) at 1h to 5.99+/-1.97% ID/g at 48 h after ip administration of RBLPL. The
      levels of radioactivity in tumor were progressive accumulation to a maximum of
      6.57+/-1.7% ID/g at 24 h. The radioactivity of (188)Re-BMEDA in ascites reached
      the maximum level of 54.89+/-5.91% ID/g at 1 h and declined rapidly with time.
      Pharmacokinetic studies revealed that the terminal half-life, total body
      clearance and area under the curve of RBLPL were 5.3-, 9.5- and 9.4-fold higher
      than that of (188)Re-BMEDA in blood, respectively. These results suggested that
      the long circulation, bioavailability and localization of RBLPL in tumor and
      ascites sites, which also demonstrate that the ip administration of RBLPL is a
      potential multifunctional nanoradiotherapeutics and imaging agents on a C26 colon
      carcinoma ascites mouse model.

PMID- 17499732
TI  - Cellular metabolic responses of PET radiotracers to (188)Re radiation in an MCF7
      cell line containing dominant-negative mutant p53.
AB  - We investigated the relations between the cell uptakes of metabolic radiotracers
      and beta-radiation pretreatment using a dominant mutant p53 (p53mt) cell line to
      evaluate the effects of p53 genes on (18)F labeled positron emission tomography
      (PET) radiotracer uptakes. METHODS: pCMV-Neo-Bam (control), which contains a neo
      resistance marker, and p53 dominant-negative mutant expression constructs were
      stably transfected into MCF7 cell line. Cells were plated in 24-well plates at
      1.0x10(5) cells for 18 h. Rhenium-188 ((188)Re) (a beta emitter) was added to the
      medium (3.7, 18.5, 37 MBq) and incubated for 24 h. We performed gamma-counting to
      determine the cellular uptakes of 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG), o-(2
      [(18)F]fluoroethyl)-l-tyrosine (FET) and 2'-[(18)F]fluoro-2'-deoxythymidine (FLT)
      (370 kBq, 60 min). Cell viabilities were determined by trypan blue staining and
      flow cytometry. RESULTS: p53mt cells showed 1.5-2-fold higher FDG uptake than
      wild-type p53 cells in basal condition, and the difference of FDG uptake was
      greater after (188)Re treatment (P<.01). FET uptake increased with (188)Re dose
      without a significant difference between p53 statuses. p53mt cells showed lower
      FLT uptake than wild-type p53 cells in basal condition, and the difference of FLT
      uptake was greater after (188)Re treatment. By cell viability testing and FACS
      analysis, p53mt cells showed lower viability and a larger apoptotic fraction (sub
      G1) than wild-type p53 cells after (188)Re treatment. CONCLUSION: We speculate
      that p53 dysfunction increases glucose and decreases thymidine metabolism in
      cancer cells and that this may be exaggerated by (188)Re beta-radiation. Our
      findings suggest that FDG could reflect tumor viability and malignant potential
      after (188)Re beta-radiation treatment, whereas FLT could be a more useful PET
      radiotracer for assessing therapeutic response to beta-radiation, especially in
      cancer cells with an altered function of p53.

PMID- 17499733
TI  - An automated one-step one-pot [(18)F]FCWAY synthesis: development and
      minimization of chemical impurities.
AB  - [(18)F]FCWAY (N-{2-[4-(2-methoxyphenyl)piperazino]}-N-(2-pyridinyl)trans-4
      fluorocyclohexanecarboxamide) has been prepared routinely as a serotonin 5-HT(1A)
      receptor ligand for clinical human studies. We have developed an automated one
      step radiosynthesis using a modified Nuclear Interface C-11 Methylation System.
      The chemical synthesis of an appropriate methanesulfonate precursor for single
      step nucleophilic substitution with [(18)F]fluoride ion and the adaptation of
      radiochemical synthesis to an automated production module were accomplished.
      Following purification of a substrate using countercurrent chromatography,
      radiochemical yield increased from 18.9+/-0.3% to 21.9+/-2.2%. In addition,
      reduction of chemical impurities from about 40% to about 20% of total mass was
      observed. Further improvements in chemical purity were achieved by minimization
      of side reactions by modification of reaction conditions and optimization of the
      high-performance liquid chromatography method for the purification of the final
      radiopharmaceutical. Optimized automated synthesis produced [(18)F]FCWAY in a
      radiochemical yield of 28+/-6% at a chemical purity of 99.3% based on the
      absorbance of FCWAY at 254 nm and with a specific activity of 3433+/-1015
      mCi/micromol at the end of bombardment, all calculated from the same 50 runs.

PMID- 17499734
TI  - Strategy for improved [(11)C]DAA1106 radiosynthesis and in vivo peripheral
      benzodiazepine receptor imaging using microPET, evaluation of [(11)C]DAA1106.
AB  - INTRODUCTION: The peripheral benzodiazepine receptor (PBR) has shown considerable
      potential as a clinical marker of neuroinflammation and tumour progression.
      [(11)C]DAA1106 ([(11)C]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)
      acetamide) is a promising positron emission tomography (PET) radioligand for
      imaging PBRs. METHODS: A four-step synthetic route was devised to prepare
      DAA1123, the precursor for [(11)C]DAA1106. Two robust, high yielding methods for
      radiosynthesis based on [(11)C]-O-methylation of DAA1123 were developed and
      implemented on a nuclear interface methylation module, producing [(11)C]DAA1106
      with up to 25% radiochemical yields at end-of-synthesis based on [(11)C]CH(3)I
      trapped. Evaluation of [(11)C]DAA1106 for in vivo imaging was performed in a
      rabbit model with microPET, and the presence of PBR receptor in the target organ
      was further corroborated by immunohistochemistry. RESULTS: The standard solution
      method produced 2.6-5.2 GBq (n=19) of [(11)C]DAA1106, whilst the captive solvent
      method produced 1.6-6.3 GBq (n=10) of [(11)C]DAA1106. Radiochemical purities
      obtained were 99% and specific radioactivity at end-of-synthesis was up to 200
      GBq/micromol for both methods. Based on radiochemical product, shorter
      preparation times and simplicity of synthesis, the captive solvent method was
      chosen for routine productions of [(11)C]DAA1106. In vivo microPET [(11)C]DAA1106
      scans of rabbit kidney demonstrated high levels of binding in the cortex. The
      subsequent introduction of nonradioactive DAA1106 (0.2 micromol) produced
      considerable displacement of the radioactive signal in this region. The presence
      of PBR in kidney cortex was further corroborated by immunohistochemistry.
      CONCLUSIONS: A robust, high yielding captive solvent method of [(11)C]DAA1106
      production was developed which enabled efficacious in vivo imaging of PBR
      expressing tissues in an animal model.

PMID- 17499735
TI  - An automatic MRI/SPECT registration algorithm using image intensity and
      anatomical feature as matching characters: application on the evaluation of
      Parkinson's disease.
AB  - Single-photon emission computed tomography (SPECT) of dopamine transporters with
      (99m)Tc-TRODAT-1 has recently been proposed to offer valuable information in
      assessing the functionality of dopaminergic systems. Magnetic resonance imaging
      (MRI) and SPECT imaging are important in the noninvasive examination of dopamine
      concentration in vivo. Therefore, this investigation presents an automated
      MRI/SPECT image registration algorithm based on a new similarity metric. This
      similarity metric combines anatomical features that are characterized by specific
      binding, the mean count per voxel in putamens and caudate nuclei, and the
      distribution of image intensity that is characterized by normalized mutual
      information (NMI). A preprocess, a novel two-cluster SPECT normalization
      algorithm, is also presented for MRI/SPECT registration. Clinical MRI/SPECT data
      from 18 healthy subjects and 13 Parkinson's disease (PD) patients are involved to
      validate the performance of the proposed algorithms. An appropriate color map,
      such as "rainbow," for image display enables the two-cluster SPECT normalization
      algorithm to provide clinically meaningful visual contrast. The proposed
      registration scheme reduces target registration error from >7 mm for conventional
      registration algorithm based on NMI to approximately 4 mm. The error in the
      specific/nonspecific (99m)Tc-TRODAT-1 binding ratio, which is employed as a
      quantitative measure of TRODAT receptor binding, is also reduced from 0.45+/-0.22
      to 0.08+/-0.06 among healthy subjects and from 0.28+/-0.18 to 0.12+/-0.09 among
      PD patients.

PMID- 17499736
TI  - Automated synthesis of 11beta-methoxy-4,16alpha-[16alpha-(18)F]difluoroestradiol
      (4F-M[(18)F]FES) for estrogen receptor imaging by positron emission tomography.
AB  - Addition of both a 4-fluoro and 11beta-methoxy group onto 16alpha
      [(18)F]fluoroestradiol ([(18)F]FES) yields 11beta-methoxy-4,16alpha-[16alpha
      (18)F]difluoroestradiol (4F-M[(18)F]FES) with potential improved properties for
      positron emission tomography (PET) imaging of estrogen receptor densities in
      breast cancer patients. In order to provide 4F-M[(18)F]FES as a
      radiopharmaceutical for clinical trials, we developed an automated synthesis
      procedure using 3-O-methoxymethyl-11beta-methoxy-4-fluoro-16,17-O-sulfuryl-16
      epiestriol as precursor. The radio synthesis involves stereoselective opening of
      the protected cyclic sulfone precursor via nucleophilic fluorination with
      [(18)F]fluoride in acetonitrile. After removal of the protecting ether and 17beta
      sulphate groups by rapid hydrolysis in acidic ethanol and subsequent reversed
      phase HPLC purification, the pure 4F-M[(18)F]FES was obtained as a sterile
      physiological saline solution in 45-50% radiochemical yield (decay corrected).
      The radiochemical purity of the final product was >98% and the effective specific
      activity (ESA) of 4F-M[(18)F]FES prepared under optimized conditions was >15,000
      Ci/mmol. The total preparation time was 110+/-5 min and the product was shown to
      be stable for at least 6 h.

PMID- 17499737
TI  - Whole-body distribution and radiation dosimetry of the dopamine transporter
      radioligand [(11)C]PE2I in healthy volunteers.
AB  - INTRODUCTION: This study reports on the biodistribution and radiation dosimetry
      of a cocaine analog, the (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'
      tolyl)nortropane (PE2I), labeled with carbon 11 ([(11)C]PE2I). [(11)C]PE2I is
      used in positron emission tomography (PET) for examination of the dopamine
      neuronal transporter (DAT). DAT radioligands are often used to evaluate the
      progression of Parkinson's disease or the efficiency of neuroprotective
      therapeutics, and, typically, these studies required several successive PET
      scans. METHODS: In three healthy male volunteers, whole-body scans were performed
      up to 2 h following intravenous injection of 321+/-6 MBq of [(11)C]PE2I. For each
      subject, regions of interest were defined over all visible organs to generate
      time-activity curves and calculate the percentage of injected activity. Time
      activity data were fitted to a monoexponential model, as an uptake phase followed
      by a mono-exponential washout, or bi-exponential model to obtain residence times.
      With the use of the MIRD method, several source organs were considered in
      estimating residence time and mean effective radiation absorbed doses. RESULTS:
      Blood pressure and ECG findings remained unchanged after radioligand injection.
      The primary route of clearance was renal. Ten minutes after injection, high
      activities were observed in the kidneys, urinary-bladder, stomach, liver,
      salivary glands and brain. The urine bladder wall, stomach and liver received the
      highest absorbed doses. The average effective dose of [(11)C]PE2I was estimated
      to be 6.4+/-0.6 microSv/MBq. CONCLUSION: The amount of [(11)C]PE2I required for
      adequate DAT PET imaging results in an acceptable effective dose equivalent
      permitting two or three repeated cerebral PET studies, with the injection of 222
      MBq for each study.

PMID- 17499739
TI  - Influence of reproductive activity, sex steroids, and seasonality on epigonal
      organ cellular proliferation in the skate (Leucoraja erinacea).
AB  - In elasmobranchs, the epigonal organ, a unique leukopoietic immune tissue, is
      associated with the gonads. As the ovaries increase in size during reproductive
      activity, the overall mass of the epigonal organ does not change. However,
      immunohistochemistry (proliferating cell nuclear antigen Ab) demonstrated more
      proliferative activity and extravasation of epigonal leukocytes from blood
      vessels in reproductively active (RA) skates (Leucoraja erinacea) than in non
      reproductively active (NRA) skates. In addition, [(3)H]thymidine incorporation
      was greater in epigonal leukocytes from RA skates than in leukocytes from NRA
      skates. Plasma from RA skates, but not from NRA skates, increased proliferation
      of epigonal leukocytes in vitro, an effect that was not seen using steroid-free
      plasma. In contrast to the stimulatory effect of plasma on leukocyte
      proliferation, addition of steroids (estrogen, progesterone, testosterone, and
      dexamethasone) in vitro decreased [(3)H]thymidine incorporation. While the
      inhibitory response to steroids was seasonally variable, (3)[H]thymidine
      incorporation was always highest in RA animals, in which plasma steroid levels
      were also consistently highest. These studies suggest functional interactions
      between reproductive and immune tissues in the skate, and that cellular turnover
      in epigonal tissue may be influenced by gonadal activity.

PMID- 17499738
TI  - Seasonal changes in CRF-I and urotensin I transcript levels in masu salmon:
      correlation with cortisol secretion during spawning.
AB  - Pacific salmon employ a semelparous reproductive strategy where sexual maturation
      is followed by rapid senescence and death. Cortisol overproduction has been
      implicated as the central physiologic event responsible for the post-spawning
      demise of these fish. Cortisol homeostasis is regulated through the action of
      hormones of the hypothalamus-pituitary-interrenal (HPI) axis. These include
      corticotropin-releasing factor (CRF) and urotensin-I (UI). In the present study,
      masu salmon (Oncorhynchus masou) were assayed for changes in the levels CRF-I and
      UI mRNA transcripts by quantitative real-time PCR (qRT-PCR). These results were
      compared to plasma cortisol levels in juvenile, adult, and spawning masu salmon
      to identify specific regulatory factors that appear to be functionally associated
      with changes in cortisol levels. Intramuscular implantation of GnRH analog
      (GnRHa) capsules was also used to determine whether GnRH influences stress
      hormone levels. In both male and female masu salmon, spawning fish experienced a
      5- to 7-fold increase in plasma cortisol levels relative to juvenile non-spawning
      salmon. Changes in CRF-I mRNA levels were characterized by 1-2 distinctive short
      term surges in adult masu salmon. Conversely, seasonal changes in UI mRNA levels
      displayed broad and sustained increases during the pre-spawning and spawning
      periods. The increases in UI mRNA levels were positively correlated (R(2)=0.21
      male and 0.26 female, p<0.0001) with levels of plasma cortisol in the pre
      spawning and spawning periods. Despite the importance of GnRH in sexual
      maturation and reproduction, the administration of GnRHa to test animals failed
      to produce broad changes in CRF-I, UI or plasma cortisol levels. These findings
      suggest a more direct role for UI than for CRF-I in the regulation of cortisol
      levels in spawning Pacific salmon.

PMID- 17499740
TI  - Sexual behavior in ewes and other domestic ruminants.
AB  - Similarities as well as differences across species in the control of sexual
      behavior are helping to fully understand the subtle relations between physiology
      and eco-ethological constraints and how the brain integrates such information. We
      will illustrate this with sexual behavior in domestic ruminants and especially
      ewes. Females of these species like humans, but unlike rodents, have a long
      luteal phase. A prolonged exposure to progesterone (Pg) before the preovulatory
      estradiol rise is necessary for estrous behavior to be displayed. Estradiol
      action and receptor localization is very similar to that observed in other
      species. But not too surprisingly, the role of Pg is rather different with a
      priming effect not observed in rodents. However, as in rodents, Pg also has an
      inhibitory effect, is necessary for the display of proceptivity and is
      responsible for the timing of the different periovulatory events. These steroids
      act on the central nervous system in similar areas across mammalian species to
      regulate estrous behavior. Steroid fluctuations during the estrous cycle cause
      changes in catecholaminergic activity in the hypothalamus. Interestingly, these
      neurotransmitters seem to have very similar effects in ewes and rats as
      illustrated by the norepinephrine rise after male-female interactions observed in
      both species. Similar comparisons can be made regarding the action of some
      neuropeptides, including oxytocin and GnRH, and more integrative processes like
      sexual differentiation and modulation of reproduction by social interactions.
      Data on sheep, goats and cows will be compared with those of rodents.

PMID- 17499741
TI  - Resveratrol inhibits expression and binding activity of the monocyte chemotactic
      protein-1 receptor, CCR2, on THP-1 monocytes.
AB  - Monocyte chemotactic protein-1 and its receptor, CCR2, play a key role in
      atherosclerosis. We determined the effect of the polyphenol, resveratrol, on CCR2
      and the mechanisms involved. Resveratrol treatment inhibited 125I-MCP-1 binding
      to THP-1 cells; 31, 56, 84% decrease for 10, 50 and 100 microM resveratrol, in
      the absence of any effect on receptor affinity. The inhibitory effect of
      resveratrol on 125I-MCP-1 binding to THP-1 cells and on CCR2 protein expression
      determined by FACS analysis was attenuated by treatment with L-NAME (NOS
      inhibitor), PD98059 (MAPK inhibitor) and LY294002 (PI3K inhibitor), whereas
      neither X/XO (reactive oxygen species generator) nor ICI182780 (estrogen receptor
      antagonist) had any effect. Concomitant with a decrease in CCR2 protein
      expression, resveratrol inhibited THP-1 CCR2 mRNA levels, in the absence of any
      effect on its stability; 26 and 45% inhibition at 10 and 50 microM resveratrol,
      respectively. This effect was not altered by co-treatment with L-NAME, PD98059 or
      ICI182780, but was potentiated by LY294002 and X/XO. CONCLUSIONS: Resveratrol
      inhibits monocyte CCR2 binding activity in an NO-, MAPK- and PI3K-dependent
      manner, whereas it inhibits CCR2 mRNA in an NO- and MAPK-independent, PI3K
      dependent manner. These inhibitory effects of resveratrol on chemokine receptor
      binding and expression may contribute, in part, to its cardiovascular protective
      activity in vivo.

PMID- 17499742
TI  - Skin autofluorescence is elevated in patients with stable coronary artery disease
      and is associated with serum levels of neopterin and the soluble receptor for
      advanced glycation end products.
AB  - AIMS: To investigate whether skin autofluorescence (AF), a non-invasive marker
      for advanced glycation end products (AGEs), is elevated in stable coronary artery
      disease (sCAD) and to investigate its relationship with serum levels of the
      soluble receptor for AGEs (sRAGE), neopterin and C-reactive protein (CRP).
      METHODS AND RESULTS: Skin AF and serum levels of sRAGE, neopterin and CRP were
      assessed in 63 sCAD patients (mean age: 64.7+/-10.5 years), comprising 78% males,
      19% subjects with diabetes, and 22% current smokers and in 33 (mean age: 63.4+/
      10.0 years) healthy non-diabetic and non-smoking age and gender matched controls.
      Skin AF was significantly increased in sCAD compared with controls, irrespective
      of diabetes, current smoking and renal function. Levels of sRAGE (standardized
      beta: 0.43 (explaining 17% of variance in skin AF); P<0.001), neopterin (beta:
      0.36 (11%); P=0.003) and glucose (beta: 0.29 (8%); P=0.0011) as well as current
      smoking (beta: 0.26 (6%); P=0.024) were independently associated with skin AF
      (R(2) 0.42), whereas the association of gender, former smoking, body mass index,
      CRP, lipids, creatinine clearance and pulse pressure with skin AF was not
      significant in this model. CONCLUSION: These data demonstrate that skin AF is
      elevated in sCAD and is related to sRAGE and neopterin, making it an easily
      applicable tool to improve our understanding of inflammatory and oxidative stress
      in cardiovascular disease.

PMID- 17499743
TI  - Low expression of cell-surface thromboxane A2 receptor beta-isoform through the
      negative regulation of its membrane traffic by proteasomes.
AB  - Human thromboxane A(2) receptor (TP) consists of two alternatively spliced
      isoforms, TP alpha and TP beta, which differ in their cytoplasmic tails. To
      examine the functional difference between TP alpha and TP beta, we searched
      proteins bound to C termini of TP isoforms by a yeast two-hybrid system, and
      found that proteasome subunit alpha 7 and proteasome activator PA28 gamma
      interacted potently with the C terminus of TP beta. The binding of TP beta with
      alpha 7 and PA28 gamma was confirmed by co-immunoprecipitation and pull-down
      assays. MG-132 and lactacystin, proteasome inhibitors, increased cell-surface
      expression of TP beta, but not TP alpha. Scatchard analysis of [(3)H]SQ29548
      binding revealed that the B(max) was higher in transiently TP alpha-expressing
      cells than TP alpha-expressing cells. In addition, TP-mediated phosphoinositide
      hydrolysis was clearly observed in TP alpha-, but not TP beta-expressing cells.
      These results suggest that TP beta binds to alpha 7 and PA28 gamma, and the cell
      surface expression of TP beta is lower than that of TP alpha through the negative
      regulation of its membrane traffic by proteasomes.

PMID- 17499744
TI  - Regulation of luteal prostaglandin F(2 alpha) production and its relevance to
      cell death: an in vitro study using rat dispersed luteal cells.
AB  - We investigated the mechanism by which rat luteal cells produce prostaglandin F(2
      alpha) (PGF(2 alpha)) and its relevance to cell death in vitro. Treatment with
      progesterone (P4) of dispersed luteal cells prepared from rats on day 9 of
      pseudopregnancy caused dose-dependent inhibition of PGF(2 alpha) secretion.
      Cytokines, tumor necrosis factor alpha (TNFalpha) or interferon gamma (IFN gamma)
      alone had no or modest regulatory effects. Arachidonyl trifluoromethyl ketone
      (AACOCF(3)), a specific group IVA phospholipase A(2) inhibitor, depressed both
      basal and cytokine-regulated PGF(2 alpha) production. A combination of TNFalpha
      and IFN gamma stimulated PGF(2 alpha) synthesis and cytotoxicity (both, P<0.05).
      Agonistic anti-Fas antibody challenge caused a significant cytotoxic effect but
      without affecting PGF(2 alpha) production. The present data suggest that P4
      inhibits and TNFalpha and IFN gamma cooperatively stimulate PGF(2 alpha) release
      by rat luteal cells. They also suggest that luteal cell death induced by
      TNFalpha/IFN gamma and Fas stimulation seems to occur via distinct signaling
      pathways involving PGF(2 alpha) production.

PMID- 17499745
TI  - Chronic renal failure-induced multiple-organ injury in rats is alleviated by the
      selective CysLT1 receptor antagonist montelukast.
AB  - Chronic renal failure (CRF) is associated with oxidative stress that promotes
      production of reactive oxygen species and cytokine release. We aimed to
      investigate the possible protective effect of montelukast, a CysLT1 receptor
      antagonist, against oxidative damage in a rat model of CRF, induced by 5/6
      reduction of renal mass. Male Wistar albino rats were randomly assigned to either
      the CRF group or the sham-operated control group, which received saline or
      montelukast (10mg/kg, i.p.) for 4 weeks. At the end of the 4 weeks, rats were
      decapitated and trunk blood was collected. Creatinine, blood urea nitrogen and
      lactate dehydrogenase (LDH) activity were measured in the serum samples, while
      leukotriene B(4), TNF-alpha, IL-1 beta, IL-6, total antioxidant capacity (AOC)
      and leukocyte apoptosis were assayed in plasma samples. Kidney, lung, heart and
      brain tissue samples were taken for the determination of tissue malondialdehyde
      (MDA), glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Oxidant
      induced tissue fibrosis was determined by tissue collagen contents, and the
      extent of tissue injuries was analyzed microscopically. CRF caused significant
      decreases in tissue GSH and plasma AOC, which were accompanied with significant
      increases in MDA levels, MPO activities, and collagen contents of all the studied
      tissues, while the circulating levels of the pro-inflammatory mediators, LDH
      activity, creatinine and BUN were elevated. Montelukast treatment reversed all
      these biochemical indices, as well as histopathological alterations induced by
      CRF. Similarly, flow cytometric measurements revealed that leukocyte apoptosis
      was increased in CRF group, while montelukast reversed this effect. In
      conclusion, CRF-induced oxidative tissue injury occurs via the activation of pro
      inflammatory mediators and by neutrophil infiltration into tissues, and that
      protective effects of montelukast on CRF-induced injury can be attributed to its
      ability to inhibit neutrophil infiltration and apoptosis, to balance oxidant
      antioxidant status and to regulate the generation of pro-inflammatory mediators.

PMID- 17499746
TI  - Dioleoyl phosphatidic acid increases intracellular Ca2+ through endogenous LPA
      receptors in C6 glioma and L2071 fibroblasts.
AB  - Phosphatidic acid (PA) increased intracellular Ca(2+) concentration ([Ca(2+)](i))
      in C6 rat glioma and L2071 mouse fibroblast cells. Dioleoyl PA (PA, 18:1) was the
      most efficacious, followed by dipalmitoyl PA (16:0 PA) and dimyristoyl PA (14:0
      PA). Lysophosphatidic acid (LPA) also increased the [Ca(2+)](i) in the both
      cells. PA desensitized LPA-induced Ca(2+) response completely in C6 cells, but
      partly in L2071 cells. Treatment of pertussis toxin (PTX), a specific inhibitor
      of G(i/o)-type G proteins, completely ameliorated LPA- and PA-induced Ca(2+)
      response in C6 cells. However, in L2071 cells, PTX inhibited PA-induced Ca(2+)
      increase by 80% and LPA-induced one by 20%. Ki16425, a specific inhibitor of
      LPA(1)/LPA(3) receptors, completely inhibited both LPA- and PA-induced Ca(2+)
      responses in C6 cells. On the other hand, in L2071 cells, Ki16425 completely
      inhibited PA-induced Ca(2+) response, but partly LPA-induced one. VPC32183,
      another specific inhibitor of LPA(1)/LPA(3) receptors, completely inhibited LPA-
      and PA-induced Ca(2+) responses in both C6 and L2071 cells. Therefore, PA and LPA
      appear to increase [Ca(2+)](i) through Ki16425/VPC32183-sensitive LPA receptor
      coupled to PTX-sensitive G proteins in C6 cells. In L2071 cells, however, LPA
      increases [Ca(2+)](i) through Ki16425-insensitive LPA receptor coupled to PTX
      insensitive G proteins and Ki16425-sensitive LPA receptor coupled to PTX
      sensitive G protein, whereas PA utilized only the latter pathway. Our results
      suggest that PA acts as a partial agonist on endogenous LPA receptors, which are
      sensitive to Ki16425 and coupled to PTX-sensitive G protein, but not on LPA
      receptors, which are not sensitive to Ki16425 and coupled to PTX-insensitive G
      protein.

PMID- 17499747
TI  - Partial hepatectomy activates production of the pro-mitotic intermediates of the
      sphingomyelin signal transduction pathway in the rat liver.
AB  - Sphingomyelin signal transduction pathway regulates cell cycle through a number
      of lipid second messengers, which stimulate cell proliferation (sphingosine-1
      phosphate), initiate growth arrest or induce apoptosis (sphingosine, ceramide).
      To asses the functioning of sphingomyelin pathway during liver regeneration after
      partial hepatectomy in rat (PH) we measured the content of sphingomyelin (SM),
      ceramide (CER), sphingosine (SPH), sphingosine-1-phosphate (S1P), the activity of
      neutral Mg(2+)-dependent and acidic sphingomyelinases and ceramidases, in the
      remnant liver lobes during the first 24h after PH in rat. The activity of acidic
      ceramidase was highest at 4th hour after PH, whereas the activity of neutral
      ceramidases peaked at 12th hour after the operation. At these time points the
      activity Mg(2+)-dependent sphingomyelinase was also elevated, together with the
      content of SPH, S1P and the ratio of S1P to CER. The activity of acidic
      sphingomyelinase increased gradually from 4th to 24th hour after the operation.
      This was accompanied by significant increase in the content of ceramide between
      4th and 24th hour and reduction in the content of S1P and S1P to CER ratio. It is
      concluded that partial hepatectomy induces production of the pro-mitogenic
      intermediates of sphingomyelin signaling pathway during the first 12h of liver
      regeneration in rat.

PMID- 17499748
TI  - Interactive actions of prostaglandin and epidermal growth factor to enhance
      proliferation of granulosa cells from chicken prehierarchical follicles.
AB  - The interactive actions of prostaglandin (PG) and epidermal growth factor (EGF)
      on proliferation of granulosa cells was investigated in prehierarchical small
      yellow follicles (SYF) of laying hens. The granulosa layers were dispersed into
      single cells by 12.5 microg/ml collagenase. After 16 h pre-incubation in 0.5%
      fetal calf serum-supplemented medium, the medium was replaced with serum-free
      medium. Immunocytochemical staining showed that granulosa cells expressed EGF and
      its receptor, and their expression was increased by PGE(1) (1-100 ng/ml) or
      forskolin (10(-7) to 10(-5)M) treatments. EGF receptor was also induced by its
      ligand EGF. The specific prostaglandin synthase inhibitors SC560 (for COX-1) and
      NS398 (for COX-2) suppressed EGF-stimulated increase of the granulosa cell
      number. Furthermore, the effect of EGF was confirmed by the immunocytochemical
      staining of the proliferating cell nuclear antigen in granulosa cells. Though EGF
      promoted the expression of both COX-1 and COX-2, the rescue experiment indicated
      that combined treatment of PGE(1) showed better rescuing effect on NS398
      inhibition than SC560 at 10(-6)M, which implies COX-2 plays the predominant role
      in mediating EGF action. The above results indicate that reciprocal stimulation
      of intracellular PG and EGF production may enhance proliferation of granulosa
      cells, hence to facilitate development of chicken prehierarchical follicles.

PMID- 17499749
TI  - TNF-alpha modulates hepatic Na+-K+ ATPase activity via PGE2 and EP2 receptors.
AB  - The effect of TNF-alpha on liver Na(+)-K(+) ATPase was studied in Sprague-Dawley
      rats and in HepG2 cells. TNF-alpha was injected intraperitoneally to rats and 4h
      later the liver was isolated and the activity and protein expression of hepatic
      Na(+)-K(+) ATPase studied. The cytokine caused a significant down-regulation of
      the ATPase and a decrease in its activity. This effect disappeared in presence of
      indomethacin, an inhibitor of COX enzymes, and PGE2 injected to the animals
      imitated the effect of TNF-alpha. The observed in vivo effects of TNF and PGE2 on
      the pump appeared again when HepG2 cells were treated with the cytokine or the
      prostaglandin. The application of different agonist and antagonist to EP
      receptors showed that the effect of PGE2 is mediated via EP2 receptors. It was
      concluded that TNF-alpha induces in hepatocytes, PGE2 production which in turn
      reduces the activity and protein expression of the Na(+)-K(+) ATPase by
      activating EP2 receptors.

PMID- 17499750
TI  - Optimization of a solid phase extraction procedure for prostaglandin E2, F2 alpha
      and their tissue metabolites.
AB  - The primary prostaglandins PGE(2) and PGF(2 alpha) are metabolized in tissues by
      a series of enzymatic and non-enzymatic reactions. To measure metabolic rates and
      individual reaction rates it is necessary to extract the parent prostaglandins
      and metabolites before the separation and quantification of each compound is
      achieved. Here we have established and optimized a solid phase extraction (SPE)
      procedure to recover PGE(2), PGF(2 alpha) and their six enzymatic and non
      enzymatic tissue metabolites from aqueous solutions including urine, plasma and
      tissue homogenate. We have used octadecyl-bonded silica gel as the stationary
      phase and methanol-water mixtures as binary mobile phases. The volumes and
      concentrations of the washing and elution solutions were optimized individually
      for each PG. Recoveries of all PG standards were quantitative except for PGEM,
      which was recovered at 80% efficiency. Biological matrix components interfered
      with the extraction in a PG- and matrix-specific fashion. Inclusion of 1% formic
      acid in the loading mixture raised recoveries from urine, plasma and tissue
      homogenate to >or=90%. This SPE method is the first that has been optimized by
      systematic elution studies for PGE(2), PGF(2 alpha) and the complement of their
      tissue metabolites. The procedure is simple, robust and can serve as an effective
      pre-purification step before downstream separation and quantification of each
      tissue metabolite of PGE(2) and PGF(2 alpha) from complex biological matrices.

PMID- 17499751
TI  - Relaxing effects of 5-oxo-ETE on human bronchi involve BK Ca channel activation.
AB  - The present study investigated the ability of 5-oxo-EicosaTetraEnoic acid (5-oxo
      ETE) for modulating airway smooth muscle (ASM) tone in human bronchi. 5-Oxo-ETE
      induced a concentration-dependent relaxing effect on human bronchi pre-contracted
      with methacholine (MCh) and arachidonic acid (AA). This relaxing response was
      highly sensitive to Iberiotoxin (IbTx), a large conducting Ca(2+)-activated K(+)
      channel (BK(Ca)) inhibitor. Furthermore, microelectrode measurements revealed
      that 5-oxo-ETE (0.1-10 microM) hyperpolarizes the membrane potential of human
      bronchial ASM cells. These hyperpolarizing effects were also inhibited in the
      presence of 10nM IbTx. Lastly, 5-oxo-ETE was shown to directly activate
      reconstituted BK(Ca) channels derived from human airway smooth muscles. In
      summary, the 5-oxo-ETE eicosanoid activates a specific K(+) conductance, involved
      in membrane hyperpolarization, which in turn reduces Ca(2+) entry and facilitates
      relaxation of smooth muscle cells.

PMID- 17499752
TI  - Expression of cyclo-oxygenase-2 in macrophages associated with cutaneous melanoma
      at different stages of progression.
AB  - The biological significance of the almost constant presence of macrophages in the
      tumoral microenvironment is an issue debated by several authors. The major
      difficulty in understanding the role played by tumor-associated macrophages
      (TAMs) in tumor progression is due to the contrasting effects of TAMs found in
      different studies. In addition, there is a limited information on which of the
      many biological activities expressed by TAMs are critical in inducing stimulatory
      or inhibitory effect on tumor growth. The aim of our study was: (a) to explore to
      what extent cyclo-oxygenase-2 (COX-2) in TAMs associated with human melanoma is
      expressed at different stages of tumor progression; and (b) to explore whether
      COX-2 expression in TAMs is stimulated by melanoma cells. In order to answer this
      question, we determined COX-2 positive TAMs associated with cutaneous melanocytic
      nevi, in situ, invasive and metastatic melanoma. In addition, we investigated
      whether COX-2 is expressed in peritoneal thioglycollate-elicited macrophages
      after co-cultivation with murine B16 melanoma cells. We found that COX-2-positive
      TAMs, as revealed by immunohistochemical analysis, were rare in common nevi and
      "dysplastic nevi", but present in a high percentage in in situ and thin melanoma.
      COX-2-positive TAMs were also found in more advanced tumors and metastatic
      melanoma, although at a significantly lower percentage in these latter. The in
      vitro protocol revealed that COX-2 was expressed in peritoneal macrophages upon
      contact with B16 murine melanoma cells, but not with normal murine fibroblasts.
      On the whole, the results of in vivo and in vitro studies suggest that COX-2
      expressed in TAMs appears to act as an effective biomarker of melanoma
      progression, and melanoma cells themselves might stimulate COX-2 in macrophages.

PMID- 17499753
TI  - Particle deposition in obstructed airways.
AB  - One approach to tackle the particle deposition in human lungs in close proximity
      is to develop an understanding of the particle motion in bifurcation airways.
      Chronic obstructive pulmonary disease (COPD) is one of the most common diseases
      in humans. COPD always results in inflammation that leads to narrowing and
      obstructing of the airways. The obstructive airways can alter the respiratory
      flow and particle deposition significantly. In order to study the effect of
      obstruction on particle deposition, four three-dimensional four-generation lung
      models based on the 23-generation model of Weibel [1963. Morphometry of the Human
      Lung. New York Academic Press, Springer, Berlin.] have been generated. The fully
      three-dimensional incompressible laminar Navier-Stokes equations are solved using
      computational fluid dynamics (CFD) solver on structured hexahedral meshes.
      Subsequently, a symmetric four-generation airway model serves as the reference
      and the other three models are considered to be obstructed at each generation,
      respectively. The calculation results show that the obstructive airway has
      significant influence on the particle deposition down-stream of the obstruction.
      The skewed velocity profile in the bifurcation airway is modified by the throat;
      consequently, more particles impact on the divider which results in higher
      deposition efficiency.

PMID- 17499754
TI  - Detection of nitrated benzodiazepines by indirect laser-induced fluorescence
      detection on a microfluidic device.
AB  - Recently there has been concern regarding the use of flunitrazepam and other low
      dose benzodiazepines in drug-facilitated sexual assault. These compounds are
      placed in drinks of unsuspecting victims and produce a sedative effect with
      anterorgrade amnesia. Chip-based microfluidic systems can provide a quick and
      disposable procedure for the detection of flunitrazepam and other nitrated
      benzodiazepines used in these crimes. This paper describes the application of
      indirect quenching of cyanine dye (Cy5) for detection of nitrated
      benzodiazepines. The separation is performed on a microfluidic device with a
      separation channel 8 cm long and 50 microm wide and utilizes indirect
      fluorescence detection with 635 nm laser excitation. The optimization of the
      separation using micellar electrokinetic chromatography with organic modifiers is
      described. A borate buffer containing 2.6 microM Cy5 dye, 15 mM sodium dodecyl
      sulphate (SDS) and 20% methanol is used. Complete separation of four target drugs
      occurs in under 2 min with limits of detection in the low microg/ml range.
      Overall the method provides a rapid and simple analysis for the presence of
      nitrated benzodiazepines in beverages and other similar preparations.

PMID- 17499755
TI  - Development and validation of a rapid headspace gas chromatography-mass
      spectrometry method for the determination of diethyl ether and acetone residues
      in Tween extracts of shellfish intended for mouse bioassay for diarrhoetic
      toxins.
AB  - A validated analytical method using headspace capillary gas chromatography with
      mass spectrometric detection, which utilises deuterated analogues of the target
      analytes as internal standards has been developed and applied to the
      determination of acetone and diethyl ether in Tween extracts of cockles
      (Cerastoderma edule) and mussels (Mytilus edulis) destined for mouse bioassay for
      lipophilic toxins. The optimal conditions for headspace incubation were 50
      degrees C for 6 min. The limits of detection and quantitation for both DEE and
      acetone were 2 and 7 microg/mL, respectively, based on signal to noise ratios of
      3 and 10, respectively. The linear dynamic range of the instrument was 0 to ca.
      4000 microg/mL for both acetone (r(2)=0.995) and DEE (r(2)=0.999). Tween extracts
      of cockle spiked with acetone and DEE at 3925 and 3570 microg/mL, respectively,
      gave mean (n=3) recovery figures of 101% (RSD=13.1%) for acetone and 90%
      (RSD=7.3%) for DEE in cockle matrix. The corresponding figures obtained from
      spiked mussel matrix were 114% (RSD=5.7%) for acetone and 95% (RSD=6.7%) for DEE,
      respectively, which were within acceptable range.

PMID- 17499756
TI  - Gas chromatography-mass spectrometry analysis of ketamine and its metabolites--a
      comparative study on the utilization of different derivatization groups.
AB  - Method of chemical derivatization is the main difference among the GC-MS based
      methodologies reported for the analysis of ketamine and its major metabolites
      (norketamine and dehydronorketamine). These approaches included acylation and
      silylation resulting in the formation of acetyl, trifluoroacetyl,
      heptafluorobutyryl, and pentafluorobenzoyl (for acylation); and possibly
      trimethylsilyl and t-butyldimethylsilyl (for silylation) derivatives. This study
      evaluates the merits of these approaches based on the following criteria:
      reaction yields and ionization efficiency of the derivatization products;
      chromatographic characteristics; and cross-contributions to the intensities of
      ions designating the analyte and the internal standard. Pentafluorobenzoyl
      derivatives were found to provide the best performance characteristics.

PMID- 17499758
TI  - Rodlike silica and titania objects templated on extremely dilute aqueous
      dispersions of self-assembled sodium lithocholate nanotubes.
AB  - Simple methods for preparation of mesoporous rodlike silica and titania
      nanoobjects, some with exceedingly high aspect ratios, are described. They
      involve hydrolytic sol-gel processes using nanotubes from aqueous assemblies of
      very dilute (0.1 wt%) sodium lithocholate as templates. Shearing of the
      lithocholate nanotubes results in aligned, templated silica rods. The relative
      rates of lithocholate self-assembly and of polymerization of the titania
      precursors, especially, appear to be important factors in templating efficiency.

PMID- 17499757
TI  - Separation and determination of warfarin enantiomers in human plasma using a
      novel polymeric surfactant for micellar electrokinetic chromatography-mass
      spectrometry.
AB  - Warfarin is a widely used oral anticoagulant which is mostly administrated as a
      racemic mixture containing equal amount of R- and S-enantiomers. The two
      enantiomers are shown to exhibit significant differences in pharmacokinetics and
      pharmacodynamics. In this study, a new chiral micellar electrokinetic
      chromatography-mass spectrometry (MEKC-MS) method has been developed using a
      polymeric chiral surfactant, polysodium N-undecenoyl-L,L-leucyl-valinate (poly
      L,L-SULV), as a pseudostationary phase for the chiral separation of (+/-)
      warfarin (WAR) and (+/-)-coumachlor (COU, internal standard). Under optimum MEKC
      MS conditions, the enantio-separation of both (+/-)-WAR and (+/-)-COU was
      achieved within 23 min. Calibration curves were linear (R=0.995 for (R)-WAR and
      R=0.989 for (S)-WAR) over the concentration range 0.25-5.0 microg/mL. The MS
      detection was found to be superior over the commonly used UV detection in terms
      of selectivity and sensitivity with LOD as low as 0.1 microg/mL in human plasma.
      The method was successfully applied to determine WAR enantiomeric ratio in
      patients' plasma undergoing warfarin therapy.

PMID- 17499759
TI  - Dynamic wetting of Boger fluids.
AB  - The impact of fluid elasticity on the dynamic wetting of polymer solutions is
      important because many polymer solutions in technological use exhibit non
      Newtonian behaviors in the high shear environment of the wedge-like flow near a
      moving contact line. Our former study [G.K. Seevaratnam, Y. Suo, E. Rame, L.M.
      Walker, Phys. Fluids 19 (2007) Art. No. 012103] showed that shear thinning
      induced by a semi-flexible high molecular weight polymer reduces the viscous
      bending near a moving contact line as compared to a Newtonian fluid having the
      same zero-shear viscosity. This results in a dramatic reduction of the dependence
      of the effective dynamic contact angle on contact line speed. In this paper, we
      discuss dynamic wetting of Boger fluids which exhibit elasticity-dominated
      rheology with minimal shear thinning. These fluids are prepared by dissolving a
      dilute concentration of high molecular weight polymer in a "solvent" of the
      oligomer of the polymer. We demonstrate that elasticity in these fluids increases
      curvature near the contact line but that the enhancement arises mostly from the
      weakly non-Newtonian behavior already present in the oligomeric solvent. We
      present evidence of instabilities on the liquid/vapor interface near the moving
      contact line.

PMID- 17499760
TI  - Monitoring Bacillus thuringiensis-susceptibility in insect pests that occur in
      large geographies: how to get the best information when two countries are
      involved.
AB  - The adoption of cotton producing insecticidal proteins of Bacillus thuringiensis,
      commonly referred to as Bt cotton, around the world has proven to be beneficial
      for growers and the environment. The effectiveness of this important genetically
      modified crop can be jeopardized by the development of resistance to Bt cotton by
      pests it is meant to control, with the possibility that this phenomenon could
      develop in one country and spread to another by means of insect migration. To
      preserve the effectiveness of this agricultural biotechnology, regulatory
      agencies have developed plans to mitigate the development of resistance, and
      research institutions constantly monitor for shifts in Bt-susceptibility in
      important pests. If Bt-resistance is detected, this finding needs to be
      corroborated by an independent laboratory according to current regulatory
      requirements; a process that presents numerous challenges. We investigated the
      biological activity of Bt-incorporated diet on Helicoverpa virescens L. after it
      was stored for several days at different temperatures. Diet stored up to nine
      days at different temperatures (-14 to 27 degrees C) produced the same biological
      effect on H. virescens as freshly-prepared diet. Elevating the temperature of Bt
      stock solution to 76 degrees C as compared to 26 degrees C yielded significantly
      higher reading of apparent Cry1Ac concentration from MVP II, but not enough to
      elicit a significant biological response when these stock solutions were
      incorporated into insect artificial diet. These findings are important
      particularly when the confirmation of resistance is done at a distant location,
      such as Mexico, or when diet is shared between laboratories, and must be stored
      for later use, as in the case of international collaboration.

PMID- 17499761
TI  - Tolerance to Bacillus thuringiensis endotoxin in immune-suppressed larvae of the
      flour moth Ephestia kuehniella.
AB  - Tolerance to Bacillus thuringiensis crystal endotoxins (Bt-toxins) is correlated
      with an elevated immune status in larvae of the flour moth Ephestia kuehniella.
      To gain more specific information about the effector pathways involved in the
      protection against the toxin, we studied the effects of Bt-toxin formulations in
      susceptible (non-induced) and tolerant (immune-induced) larvae after natural
      (parasitism-mediated) and chemical (tropolone-mediated) suppression of defence
      reactions. Although melanization in hemolymph was significantly reduced, there
      was no significant effect on susceptibility to the toxin in parasitised or
      tropolone-treated larvae. This suggests that melanization of hemolymph is
      correlated with an elevated immune status but not responsible for the observed
      tolerance to Bt-toxin. To examine whether hemolymph proteins exist in the gut
      lumen and function as pro-coagulants, we compared gut and plasma proteins of
      immune-induced with those of non-induced larvae. Here we show that the lipid
      carrier lipophorin represents a major component in the gut lumen and interacts
      with mature Bt-toxin to form a complex.

PMID- 17499762
TI  - Indication for plasma exchange for systemic necrotizing vasculidities.
AB  - Plasma exchanges (PE) are a component of regimens prescribed to treat systemic
      necrotizing vasculidities. They are also part of the best therapeutic strategy
      for virus-induced vasculidities. The combination of antiviral agents and PE has
      proven efficacy against polyarteritis nordosa. This strategy is also effective
      for human immunodeficiency virus-associated vasculitis and, unlike cytotoxic
      agents, does not jeopardize the outcome of acquired immunodeficiency syndrome.
      Concerning the vasculitis seen in the context of hepatitis C virus-related
      cryoglobulinemia, PE contribute to better outcomes but, because of the poor
      efficacies of antiviral drugs, only about half of the patients achieve definitive
      recovery and relapses are frequent. The use of PE to treat antineutrophil
      cytoplasm antibody-associated vasculidities with severe renal insufficiency leads
      to improved renal function and thus fewer patients require dialysis. Although PE
      does not improve survival, their adjunction to corticosteroids and
      immunosuppressants for patients with alveolar hemorrhage could also limit the
      severity of this severe manifestation.

PMID- 17499763
TI  - Plasma exchange for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is the most common inflammatory joint disease. Even
      though, physiopathology of rheumatoid arthritis remains unclear, the presence of
      circulating immune complexes and rheumatoid factors had led to the use of plasma
      exchange (PE). Even though PE procedures have evolved over the last decades,
      their indications and use in RA must be replaced in the context of the evolution
      of disease-modifying anti-rheumatic drugs. Results of PE and leukapheresis were
      disappointing in patients with severe and resistant RA. Conversely,
      immunoadsorption, and particularly over a Staphylococcus aureus protein A column,
      has resulted in some good responses in refractory RA patients. But, the emergence
      of effective biologics has clearly restrained their use and limited their
      indications to some rare patients with refractory and severe RA.

PMID- 17499765
TI  - A direct substrate-substrate interaction found in the kinase domain of the
      bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.
AB  - To understand the molecular basis of a phosphoryl transfer reaction catalyzed by
      the 6-phosphofructo-2-kinase domain of the hypoxia-inducible bifunctional enzyme
      6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), the crystal
      structures of PFKFB3AMPPCPfructose-6-phosphate and PFKFB3ADPphosphoenolpyruvate
      complexes were determined to 2.7 A and 2.25 A resolution, respectively. Kinetic
      studies on the wild-type and site-directed mutant proteins were carried out to
      confirm the structural observations. The experimentally varied liganding states
      in the active pocket cause no significant conformational changes. In the pseudo
      substrate complex, a strong direct interaction between AMPPCP and fructose-6
      phosphate (Fru-6-P) is found. By virtue of this direct substrate-substrate
      interaction, Fru-6-P is aligned with AMPPCP in an orientation and proximity most
      suitable for a direct transfer of the gamma-phosphate moiety to 2-OH of Fru-6-P.
      The three key atoms involved in the phosphoryl transfer, the beta,gamma-phosphate
      bridge oxygen atom, the gamma-phosphorus atom, and the 2-OH group are positioned
      in a single line, suggesting a direct phosphoryl transfer without formation of a
      phosphoenzyme intermediate. In addition, the distance between 2-OH and gamma
      phosphorus allows the gamma-phosphate oxygen atoms to serve as a general base
      catalyst to induce an "associative" phosphoryl transfer mechanism. The site
      directed mutant study and inhibition kinetics suggest that this reaction will be
      catalyzed most efficiently by the protein when the substrates bind to the active
      pocket in an ordered manner in which ATP binds first.

PMID- 17499764
TI  - Adiponectin protects against the development of systolic dysfunction following
      myocardial infarction.
AB  - There is an association between obesity and heart failure associated with LV
      dysfunction. Adiponectin is an adipocyte-derived hormone that is downregulated in
      obesity. Here, we examined the role of adiponectin in cardiac remodeling after
      myocardial infarction with loss- and gain-of-function genetic manipulations in an
      experimental model. Myocardial infarction was created in adiponectin-deficient
      (APN-KO) and wild-type (WT) mice by the permanent ligation of the left anterior
      descending (LAD) artery. For some experiments, adenoviral vectors expressing
      adiponectin or beta-galactosidase were delivered systemically. Cardiac structure
      and function were assessed by echocardiographic and Millar catheter measurements.
      Myocardial capillary density was assessed by staining with anti-CD31 antibody.
      Myocyte apoptotic activity was determined by TUNEL-staining. Myocardial
      interstitial fibrosis was evaluated by Masson's trichrome staining. APN-KO mice
      showed exacerbated left ventricular (LV) dilation, myocyte hypertrophy and
      contractile dysfunction compared with WT mice at 4 weeks after LAD ligation.
      Impaired LV function in APN-KO mice was coupled to myocyte hypertrophy, increased
      apoptotic activity and interstitial fibrosis in the remote zone, and reduced
      capillary density in the infarct border zone. No difference in infarct size was
      observed between WT and APN-KO mice. Administration of adenovirus-mediated
      adiponectin in WT mice resulted in decreased LV dilatation and improved LV
      function that was associated with increased capillary density in the infarct
      border zone and decreased myocyte hypertrophy, diminished myocardial apoptosis
      and decreased interstitial fibrosis in the remote zone. These data suggest that
      adiponectin protects against the development of systolic dysfunction after
      myocardial infarction through its abilities to suppress cardiac hypertrophy and
      interstitial fibrosis, and protect against myocyte and capillary loss.

PMID- 17499766
TI  - WITHDRAWN: Characterisation of the Intact Sensor Kinase VicK from Enterococcus
      faecalis: Direct Evidence for YycH as a Potent Modulating Signal in vitro.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17499767
TI  - Effect of the branched-chain alpha-keto acids accumulating in maple syrup urine
      disease on S100B release from glial cells.
AB  - Accumulation of the branched-chain alpha-keto acids (BCKA), alpha-ketoisocaproic
      acid (KIC), alpha-keto-beta-methylvaleric acid (KMV) and alpha-ketoisovaleric
      acid (KIV) and their respective branched-chain alpha-amino acids (BCAA) occurs in
      tissues and biological fluids of patients affected by the neurometabolic disorder
      maple syrup urine disease (MSUD). The objective of this study was to verify the
      effect of the BCKA on S100B release from C6 glioma cells. The cells were exposed
      to 1, 5 or 10 mM BCKA for different periods and the S100B release was measured
      afterwards. The results indicated that KIC and KIV, but not KMV, significantly
      enhanced S100B liberation after 6 h of exposure. Furthermore, the stimulatory
      effect of the BCKA on S100B release was prevented by coincubation with the
      energetic substrate creatine and with the N-nitro-l-arginine methyl ester (l
      NAME), a nitric oxide synthase inhibitor, indicating that energy deficit and
      nitric oxide (NO) were probably involved in this effect. Furthermore, the
      increase of S100B release was prevented by preincubation with the protein kinase
      inhibitors KN-93 and H-89, indicating that KIC and KIV altered Ca2+/calmodulin
      (PKCaMII)- and cAMP (PKA)-dependent protein kinases activities, respectively. In
      contrast, other antioxidants such as glutathione (GSH) and trolox (soluble
      vitamin E) were not able to prevent KIC- and KIV-induced increase of S100B
      liberation, suggesting that the alteration of S100B release caused by the BCKA is
      not mediated by oxidation of sulfydryl or other essential groups of the enzyme as
      well as by lipid peroxyl radicals. Considering the importance of S100B for brain
      regulation, it is conceivable that enhanced liberation of this protein by
      increased levels of BCKA may contribute to the neurodegeneration characteristic
      of MSUD patients.

PMID- 17499768
TI  - The stochastic chemomechanics of the F(1)-ATPase molecular motor.
AB  - We report a theoretical study of the F(1)-ATPase molecular rotary motor
      experimentally studied by R. Yasuda, H. Noji, M. Yoshida, K. Kinosita Jr., H.
      Itoh [Nature 410 (2001) 898]. The motor is modeled as a stochastic process for
      the angle of its shaft and the chemical state of its catalytic sites. The
      stochastic process is ruled by six coupled Fokker-Planck equations for the biased
      diffusion of the angle and the random jumps between the chemical states. The
      model reproduces the experimental observations that the motor proceeds by
      substeps and the rotation rate saturates at high concentrations of adenosine
      triphosphate or at low values of the friction coefficient. Moreover, predictions
      are made about the dependence of the rotation rate on temperature, and about the
      behavior of the F(1) motor under the effect of an external torque, especially, in
      the regime of synthesis of adenosine triphosphate.

PMID- 17499769
TI  - Ectopic ureterocele: long-term results of open surgical therapy in 54 patients.
AB  - PURPOSE: We assessed the long-term results of total reconstructive bladder
      surgery as initial treatment of ectopic ureteroceles. MATERIALS AND METHODS: Long
      term followup was evaluated in 54 children treated for ectopic ureteroceles with
      total upper and lower urinary tract reconstructive surgery between 1988 and 2003,
      with special focus on the primary outcome factors continence and urinary tract
      infections. RESULTS: Patient age at surgery was 0 to 8.8 years old (median 1.0),
      including 34 patients younger than 1 year. Followup was 2.3 to 15.6 years (median
      9.6). Of the patients 94% became continent. During the last 2 years 17% of the
      patients experienced 1 or 2 uncomplicated episodes of urinary tract infection.
      One of the patients with incontinence received chemoprophylaxis due to frequent
      urinary tract infections. Secondary endoscopic procedures were necessary in 10
      patients due to persistent reflux, and in 7 patients due to obstructive voiding.
      Reflux was present preoperatively in 33 patients, and low grade reflux was
      present postoperatively in 7, all of whom were treated conservatively. A total of
      11 children presenting with dysfunctional voiding will be or have been trained in
      biofeedback. CONCLUSIONS: The vast majority of patients treated with total
      reconstructive bladder surgery become continent and do not suffer from lower
      urinary tract symptoms during the long term. The reoperation rate is low compared
      to series beginning with endoscopic surgery. Based on the results of this study,
      we suggest that total reconstructive upper and lower urinary tract surgery be the
      treatment of choice for ectopic ureteroceles.

PMID- 17499770
TI  - Enhanced kidney stone fragmentation by short delay tandem conventional and
      modified lithotriptor shock waves: a numerical analysis.
AB  - PURPOSE: We evaluated the effectiveness of modified lithotriptor shock waves
      using computer models. MATERIALS AND METHODS: Finite element models were used to
      simulate the propagation of lithotriptor shock waves in human renal calculi in
      vivo. Kidney stones were assumed to be spherical, homogeneous, isotropic and
      linearly elastic, and immersed in a continuum fluid. Single and tandem shock wave
      pulses modified to intensify the collapse of cavitation bubbles near the stone
      surface to increase fragmentation efficiency and suppress the expansion of
      intraluminal bubbles for decreased vascular injury were analyzed. The
      effectiveness of the modified shock waves was assessed by comparing the states of
      loading in the renal calculi induced by these shock waves to those produced by
      conventional shock waves. RESULTS: Our numerical simulations revealed that
      modified shock waves produced marginally lower stresses in spherical renal
      calculi than those produced by conventional shock waves. Tandem pulses of
      conventional or modified shock waves produced peak stresses in the front and back
      halves of the renal calculi. However, the single shock wave pulses generated
      significant peak stresses in only the back halves of the renal calculi.
      CONCLUSIONS: Our numerical simulations suggest that for direct stress wave
      induced fragmentation modified shock waves should be as effective as conventional
      shock waves for fragmenting kidney stones. Also, with a small interval of 20
      microseconds between the pulses tandem pulse lithotripsy using modified or
      conventional shock waves could be considerably more effective than single pulse
      lithotripsy for fragmenting kidney stones.

PMID- 17499771
TI  - Nitrous oxide inhalation to improve patient acceptance and reduce procedure
      related pain of flexible cystoscopy for men younger than 55 years.
AB  - PURPOSE: Flexible cystoscopy in men younger than 55 years is painful despite the
      current best standard anesthesia (20 ml 2% lidocaine gel 15 minutes before
      endoscopy). The anesthetic value of lidocaine gel is debated and led us to seek
      an alternative. Nitrous oxide is a well established analgesic and anxiolytic
      agent, and it significantly reduces pain associated with transrectal ultrasound
      guided prostate biopsy. We studied its use in flexible cystoscopy in men younger
      than 55 years. MATERIALS AND METHODS: A total of 61 patients were prospectively
      randomized to receive air (31) or Entonox (30). Both groups had 3 minutes of gas
      via a breath activated facemask (either Entonox or air) before endoscopy. The gel
      control group was comprised of 8 patients who underwent cystoscopy after
      instillation of lidocaine gel. The air and Entonox groups had lidocaine gel as
      per best standard. Vital signs were recorded before, during and after cystoscopy.
      Patients completed a visual analog score for gel insertion and cystoscopy.
      RESULTS: There were no statistically significant differences between the groups
      in terms of baseline characteristics. Pain scores for cystoscopy (p<0.001) and
      intraoperative pulse rate (p=0.008) were significantly less with Entonox. Side
      effects were transient and seen more often with Entonox (p<0.05). More of the air
      group would require more analgesia (p=0.001) or a general anesthetic (p=0.011) if
      undergoing repeat cystoscopy. CONCLUSIONS: Nitrous oxide inhalation significantly
      reduces cystoscopy related pain without significant complications. We propose
      that Entonox should be the anesthetic agent of choice for men younger than 55
      years.

PMID- 17499773
TI  - Sacral neuromodulation for nonobstructive urinary retention--is success
      predictable?
AB  - PURPOSE: We investigated whether there are factors which can predict successful
      stage II (permanent) sacral nerve stimulator (InterStim) implantation for
      patients with nonobstructive urinary retention. MATERIALS AND METHODS: We
      retrospectively reviewed our sacral neuromodulation database from January 1, 1999
      to January 1, 2006. A total of 29 patients were referred to the William Beaumont
      Hospital Department of Urology for nonobstructive urinary retention. All patients
      completed a 3-day voiding log followed by test stimulation. Patients underwent
      test stimulation for a 2-week trial period. Those who experienced 50% improvement
      in void volume and/or catheterization frequency subsequently underwent permanent
      implantation. We reviewed patient charts with respect to age, sex, duration of
      retention, underlying diagnosis for retention and voiding ability. RESULTS: Of
      the 29 patients 15 were men and 14 were women. Mean patient age was 58.8+/-16
      years (range 18 to 82). The mean age of the men in the study was 55.5+/-18 years
      while the mean age of the women was 62.3+/-14 years. Although all the patients
      performed intermittent self-catheterization 18 were able to void (more than 50 cc
      per void). The remaining 11 patients had minimal (50 cc or less) or no ability to
      void. Of the 18 patients who were able to void 12 (67%) underwent successful
      permanent implantation. However, voiding improved after test stimulation in only
      2 of the 11 patients (18%) who had been unable to void. This difference was
      statistically significant (p=0.02) and suggests that pre-implantation ability to
      void can predict success of test stimulation. CONCLUSIONS: Patient ability to
      void predicts success of first stage test stimulation. Although we would still
      offer a trial of sacral neuromodulation to those with nonobstructive urinary
      retention and the inability to void, this study would allow better counseling
      regarding the likelihood of successful outcome.

PMID- 17499774
TI  - Indwelling ureteral stents and sexual health: a prospective, multivariate
      analysis.
AB  - PURPOSE: Ureteral stents are common devices in urological practice. However, a
      stent may provoke lower urinary tract symptoms that severely affect quality of
      life. We evaluated the relationship between ureteral stents and male
      erection/female sexuality. MATERIALS AND METHODS: A total of 30 men and 20 women
      undergoing ureteral stent positioning were considered. Patients affected by risk
      factors for erectile dysfunction or hormonal and metabolic alterations were
      excluded. Hystero-ovariectomy and menopause were considered exclusion criteria.
      Three questionnaires were administered before stenting and 45 to 60 days after
      stent positioning, including the International Prostate Symptom Score, the
      International Index of Erectile Function-5 for men and the Female Sexual Function
      Index for women. RESULTS: Mean age was 45 years in men and 39 years in women. The
      mean+/-SD International Index of Erectile Function-5 score was 23.2+/-1.27 and
      the mean Female Sexual Function Index score was 32.15+/-2.71 before stent
      positioning. No lower urinary tract symptoms were reported before the procedure.
      After the ureteral stent was indwelling the mean International Index of Erectile
      Function-5 score was 13.5+/-4.01 and the mean Female Sexual Function Index score
      was 23.6+/-14.66 (p=0.000 and 0.007, respectively). Of 30 men 25 reported a
      pathological International Index of Erectile Function-5 score and 6 of 20 women
      denied any sexual activity due to stent related anxiety, resulting in the minimum
      Female Sexual Function Index score. In the remaining 14 women sexual life was not
      significantly impaired by the ureteral stent (p=0.08). CONCLUSIONS: Ureteral
      stents impaired the quality of sexual life in male and female subjects. In men
      the most important distress was in regard to erectile function, probably related
      to lower urinary tract symptoms. Conversely female sexuality appeared to be
      severely impaired due to stent related psychological concerns.

PMID- 17499775
TI  - Adrenal hemorrhage.

PMID- 17499776
TI  - Outcomes of delayed hypospadias repair: implications for decision making.
AB  - PURPOSE: The current American Academy of Pediatrics recommendation is to perform
      hypospadias repair at age 6 to 12 months. Primary hypospadias repair at
      adolescence or beyond is uncommon, and there is little reported about the
      postoperative course of such patients. We report the outcomes for a series of
      patients who underwent primary hypospadias repair at age 10 years or older.
      MATERIALS AND METHODS: We identified patients seen at our institution between
      1979 and 2002 who underwent primary hypospadias repair at age 10 years or older.
      Electronic and paper charts were abstracted for baseline demographics, degree of
      hypospadias, surgical technique, complications and reoperation. RESULTS: A total
      of 31 patients were identified, with a median available followup of 14 months.
      Median patient age at first hypospadias surgery was 13 years. The location of the
      urethral meatus was distal in 19 patients, mid shaft in 7, proximal in 4 and
      undetermined in 1. A variety of techniques were used, including meatal
      advancement and glanuloplasty, meatal based flaps, island onlay flaps, Snodgrass
      repair and staged procedures. Complications were noted in 48% of patients (15 of
      31), including fistula (10), stricture (4), hematoma (2) and other complications
      (2). CONCLUSIONS: Although retrospective in nature, these data suggest that delay
      of primary hypospadias repair into the teen years or beyond may result in more
      complications than currently accepted for infant hypospadias repair.

PMID- 17499781
TI  - Durability of a single successful endoscopic polytetrafluoroethylene injection
      for primary vesicoureteral reflux: 14-year followup results.
AB  - PURPOSE: We reviewed our 14-year experience with successful single endoscopic
      subureteral polytetrafluoroethylene injection for the treatment of primary
      vesicoureteral reflux in children. MATERIALS AND METHODS: We retrospectively
      reviewed the charts of 42 patients with primary vesicoureteral reflux who were
      treated with a single successful subureteral polytetrafluoroethylene injection
      between 1989 and 1993 and followed with routine 1, 3 and 10-year voiding
      cystourethrography. RESULTS: The study included 30 girls and 12 boys 2 to 14
      years old (median age 6 years). Four patients were lost to followup. Of the 38
      remaining patients 28 had unilateral and 10 had bilateral primary vesicoureteral
      reflux. Endoscopic treatment with subureteral polytetrafluoroethylene injection
      was performed in 48 ureters. Followup ranged from 10 to 14 years (mean 12.5+/
      2.1). Voiding cystourethrography in 38 patients and 48 ureters revealed that 35
      ureters (73%) remained free of reflux, whereas reflux recurred in 13 (27%) at a
      median of 2 years. Of these 13 ureters recurring reflux was grade I to II in 5
      and grade III to V in 8. Reflux recurred in 11 of 24 ureters with grade IV to V
      reflux. Of the 13 recurrences 10 presented as febrile urinary tract infections
      and only 3 grade I recurrences were detected on voiding cystourethrography alone.
      No untoward effects were seen in any of these patients with injection of
      polytetrafluoroethylene. CONCLUSIONS: Long-term followup may be warranted after a
      single successful endoscopic injection for vesicoureteral reflux, particularly
      high grade reflux. However, followup voiding cystourethrography is unnecessary in
      patients presenting with febrile urinary tract infection.

PMID- 17499782
TI  - Myocyte apoptosis in primary obstructive megaureters: the role of decreased
      vascular and neural supply.
AB  - PURPOSE: We compared myocyte apoptosis index, microvessel density and nerve
      supply as well as muscular and collagen composition in the obstructed ureteral
      endings of children with primary obstructive megaureter and normal controls.
      MATERIALS AND METHODS: Tissue specimens were obtained during ureteral
      reimplantation in 16 patients with primary obstructive megaureter. For the
      control group normal ureteral endings were taken at autopsy from 19 age and sex
      matched children. In all specimens we determined the myocyte apoptosis index,
      number of CD31 positive microvessels, alpha-actin positive muscular component and
      number of nerve terminals. The collagen fibers were also specifically stained.
      RESULTS: The myocyte apoptosis index was higher in obstructed vesicoureteral
      junctions (10.14%+/-1.03%) compared to controls (2.11%+/-0.21%, p<0.001). Mean
      number of vascular elements per microscopic field was lower in ureteral endings
      of patients with obstructive megaureter compared to controls (p<0.001). The
      number of nerve endings was also significantly lower in obstructed ureteral
      endings. There was a negative correlation between the number of microvessels and
      myocyte apoptosis index in both study groups. In obstructed megaureters the
      number of nerve endings was also negatively correlated with myocyte apoptosis
      index but positively correlated with the number of microvessels. In obstructed
      vesicoureteral junctions the proportion of muscular component was lower and the
      proportion of collagen fibers was higher compared to normal controls. Positive
      correlation was found between the myocyte apoptosis index and the percentage of
      collagenous component in both study groups. CONCLUSIONS: Congenital defective
      vascular development may result in myocyte apoptosis, and reduction of neural
      elements and muscular components in obstructed vesicoureteral junctions.
      Subsequent substitution of connective tissue may lead to functional obstruction
      in primary obstructive megaureter.

PMID- 17499783
TI  - Urethral and bladder current perception thresholds: normative data in women.
AB  - PURPOSE: Given increased evidence of sensory dysfunction in lower urinary tract
      pathology, we determined normative current perception threshold values in the
      lower urinary tract of asymptomatic women. MATERIALS AND METHODS: After receiving
      institutional review board approval women without lower urinary tract symptoms
      underwent current perception threshold testing of the urethra and bladder using a
      Neurometer constant current stimulator. Current perception threshold values were
      determined at 3 frequencies, including 2,000 Hz (corresponding to A-beta fibers),
      250 Hz (corresponding to A-delta fibers) and 5 Hz (corresponding to C fibers).
      RESULTS: A total of 48 women with a mean age of 38 years (range 23 to 67)
      underwent current perception threshold testing. Normative values were established
      for the urethra and bladder at 2,000, 250 and 5 Hz. Median urethral current
      perception thresholds at 2,000, 250 and 5 Hz were 1.2 (IQR 0.76-1.5), 0.45 (IQR
      0.33-0.56) and 0.11 mA (IQR 0.07-0.24), respectively. Median bladder current
      perception thresholds at 2,000, 250 and 5 Hz were 4.1 (IQR 2.0-6.3), 2.3 (IQR
      0.87-5.5) and 1.4 mA (IQR 0.22-2.9), respectively. Urethral and bladder current
      perception thresholds increased significantly with subject age at all 3
      frequencies (p<0.0005). Prior pelvic surgery was associated with an increased
      bladder current perception threshold at all 3 frequencies (p<0.005) but not with
      the urethral current perception threshold. CONCLUSIONS: We report urethral and
      bladder current perception thresholds for a large sample of asymptomatic women.
      These reference values may help elucidate changes in afferent nerve function in
      women with lower urinary tract dysfunction.

PMID- 17499785
TI  - The surgical management of obstructive stents used for urethral strictures.
AB  - PURPOSE: We present our referral experience with patients who had extensive
      urethral obstruction following UroLume insertion and were treated with
      urethroplasty. MATERIALS AND METHODS: We retrospectively analyzed the records of
      13 men with urethral stricture who experienced recurrent obstruction following
      placement of a UroLume endoprosthesis. In all patients several attempts at
      urethral dilation and optical urethrotomy failed to overcome the obstruction.
      Complete excision of the obstructed urethra containing the stent with the
      surrounding periurethral fibrosis was done in all patients. In 12 patients a 1
      stage bipedicled penile island tubularized flap was used to bridge the urethral
      defect. In 1 patient 1-stage urethroplasty was performed and he is awaiting stage
      2. Followup assessment included urine flow, post-void residual urine measurement,
      retrograde urethrogram and urethroscopy at different intervals. RESULTS: Of the
      12 patients who underwent complete treatment 1 had a short segment stricture at
      the site of the distal anastomosis 3 months after catheter removal, which was
      successfully managed by internal urethrotomy. He was doing well at the 12-month
      followup. In 11 patients a successful outcome was noted immediately after
      catheter removal and it was maintained at a mean followup of 1.8 years (range 1
      to 4). CONCLUSIONS: Complete excision of the obstructed urethra containing the
      UroLume stent with the surrounding periurethral fibrosis is an important first
      step in reconstruction. Subsequent use of a 1-stage bipedicled penile island
      tubularized flap resulted in excellent long-term results. In a small subset of
      cases delayed stage 2 repair after skin inlay is a valuable option.

PMID- 17499787
TI  - Kidney transplantation in children with augmentation cystoplasty.
AB  - PURPOSE: Treatment of children with end stage renal disease, especially those
      with significant bladder dysfunction, is difficult. A high pressure and low
      capacity bladder is a major risk factor for a transplanted kidney. Cystoplasty
      can protect the kidney allograft by reducing the intravesical pressure and
      creating an appropriate capacity. The aim of this study was to evaluate the
      outcome of kidney transplantation in children with and without prior cystoplasty.
      MATERIALS AND METHODS: A total of 43 children with bladder dysfunction in urgent
      need of cystoplasty were enrolled in the study and were compared to a control
      group with regard to acute and chronic rejection rates, survival of the
      transplanted kidney, surgical complications and febrile urinary tract infection.
      RESULTS: The rates of febrile urinary tract infection and chronic rejection were
      significantly higher in patients with prior cystoplasty (p<0.001 and p=0.004,
      respectively). Also, graft loss was much more frequent in these patients (34.9%
      vs 20.9%), although this difference was not statistically significant. In
      patients with prior cystoplasty graft survival rates were 92%, 73%, 58% and 45%
      at postoperative years 1, 3, 5 and 7, respectively. In the control group these
      rates were 94%, 87%, 81% and 75%, respectively (p=0.007). CONCLUSIONS: Based on
      our findings, the survival rate of the kidney is significantly lower in children
      with prior cystoplasty, possibly due to the higher prevalence of chronic
      rejection and febrile urinary tract infection in this group.

PMID- 17499791
TI  - Vesicoscopic cross-trigonal ureteral reimplantation: a minimally invasive option
      for repair of vesicoureteral reflux.
AB  - PURPOSE: Cross-trigonal ureteral reimplantation is a commonly performed procedure
      for the correction of vesicoureteral reflux. Most previously described
      laparoscopic techniques have used an extravesical approach. A "vesicoscopic"
      technique is analogous to standard open cross-trigonal repair in principle,
      except that 3 ports with insufflation of the bladder are used to perform the
      ureteral reimplantation. MATERIALS AND METHODS: A retrospective review was
      performed of patients treated for primary vesicoureteral reflux with either
      vesicoscopic or open ureteral reimplantation. For patients with vesicoscopic
      reimplantation a 5 mm port is placed in the dome of the bladder and 2, 3 mm ports
      are placed laterally. The ureters are mobilized transvesically, cross-trigonal
      submucosal tunnels are made and the ureters are sutured in place with
      intracorporeal suturing. The bladder ports are closed and a urethral catheter is
      left indwelling for 36 hours. Among the open reimplantation group 38 patients
      underwent cross-trigonal ureteral reimplantation, 2 underwent extravesical
      ureteral reimplantation and 2 were excluded due to insufficient records. Followup
      imaging for both groups included ultrasonography at 1 month and voiding
      cystography at 3 months postoperatively. RESULTS: A total of 52 consecutive
      children underwent vesicoscopic ureteral reimplantation with 1 patient converted
      to open intravesical reimplantation, and 40 consecutive controls underwent open
      ureteral reimplantation. Postoperative vesicoureteral reflux resolution rates for
      the vesicoscopic and open groups were 91% (42 of 46 patients) and 97% (31 of 32
      patients), respectively. Mean patient age and mean maximal grade of
      vesicoureteral reflux in the vesicoscopic and open groups were 5.7 and 4.0 years
      (p=0.001), and 2.8 and 3.2 (p=0.036), respectively. Mean operative times for
      vesicoscopic and open procedures were 199 and 92 minutes, respectively (p=0.001).
      While the average length of hospital stay of 2 days was similar between the
      groups (p=0.122), less oral and intravenous analgesia was needed postoperatively
      in the vesicoscopic group (p=0.001 and p=0.005, respectively). Complications of
      vesicoscopic ureteral reimplantation included urinary leakage in 1 child, bladder
      stones in 1 and bilateral ureteral obstruction in 1. There were no complications
      in the open group. CONCLUSIONS: There is an ever increasing trend toward
      minimally invasive surgery. Our preliminary results indicate that vesicoscopic
      ureteral reimplantation is an effective procedure with minimal morbidity.
      Although success rates for vesicoureteral reflux resolution were slightly lower
      in the vesicoscopic group in this study, the favorable results of other series
      and the improvement in postoperative discomfort observed here suggest that this
      technique may be a reasonable option in the management of vesicoureteral reflux.
      Further refinement of the technique and critical analysis of the long-term
      outcomes are needed to understand fully its place in the treatment of
      vesicoureteral reflux.

PMID- 17499792
TI  - Biomechanical properties of vaginal tissue. Part 1: new experimental protocol.
AB  - PURPOSE: We established a reliable experimental protocol to characterize the
      biomechanical properties of vaginal tissue and guarantee good test repeatability.
      MATERIALS AND METHODS: Because of the large quantities of tissue required to
      establish the protocol, we worked on ewes according to animal ethics laws. To
      study the mechanical properties of ewe vaginal tissue we used unidirectional
      tension tests at a constant deformation rate. Rupture tests were performed under
      different experimental conditions to analyze the influence of each condition.
      RESULTS: Tissue underwent exhaustive tests. The parameters studied were sampling,
      freezing, preservation conditions, hygrometry and temperature during vaginal
      tissue tests, and the rate of deformation during tests. As previously noted,
      vaginal tissue is anisotropic and the collection has been tested previously. We
      noted that freezing tissue had no consequences on the mechanical response of
      tissue during unidirectional tension testing. The experimental conditions that we
      defined (temperature, hygrometry and rate of deformation) allowed us to have
      reproducible tests. CONCLUSIONS: Results and analyses allowed us to determine the
      best reference protocol.

PMID- 17499794
TI  - Increased SKP2 and CKS1 gene expression contributes to the progression of human
      urothelial carcinoma.
AB  - PURPOSE: SKP2 and CKS1 promote aggressive tumor behavior via the regulation of
      p27 degradation. Our previous DNA microarray analysis of human urothelial
      carcinoma and normal urothelial epithelium showed that in urothelial carcinoma
      the 2 most highly up-regulated genes among SKP2-p27 interaction related genes are
      SKP2 (4.7-fold) and CKS1 (2.2-fold). We hypothesized that SKP2 and CKS1 gene
      expression is associated with urothelial carcinoma invasiveness and prognosis.
      MATERIALS AND METHODS: A total of 84 urothelial carcinoma specimens from patients
      with bladder (71) and upper urinary tract (13) cancer were examined by real-time
      reverse transcriptase-polymerase chain reaction and immunohistochemical study.
      RESULTS: Real-time reverse transcriptase-polymerase chain reaction showed that
      the average mRNA expression level of SKP2 and CKS1 significantly correlated with
      tumor stage, that is superficial vs invasive urothelial carcinoma (SKP2 and CKS1,
      p<0.001 and 0.006) and grade (p<0.001 and 0.009, respectively). Of the
      superficial urothelial carcinomas examined the SKP2 and CKS1 expression level was
      significantly higher in pT1 than in pTa samples (p=0.005 and 0.017,
      respectively). Immunohistochemical expression patterns of SKP2 and CKS1 also
      significantly correlated with tumor stage (p<0.001 and 0.048) and grade (p=0.003
      and 0.025, respectively). In contrast, p27 expression inversely correlated with
      tumor stage and grade (p<0.001 and 0.011, respectively). Logistic regression
      analysis revealed that while SKP2 mRNA expression was a significant dependent
      predictor of p27 expression (p=0.021), there was no correlation between CKS1 mRNA
      expression and p27 (p=0.748). Kaplan-Meier curves and log rank tests revealed
      that the high mRNA expression levels of SKP2 and CKS1 had a significant adverse
      effect on prognosis (p=0.043 and 0.003, respectively). CONCLUSIONS: Our results
      suggest that SKP2 has a major role in the regulation of p27 degradation and CKS1
      has a supporting role for SKP2 function in human urothelial carcinoma.

PMID- 17499795
TI  - Syringocele of Cowper's gland duct: an increasingly common rarity.

PMID- 17499797
TI  - Impact of unilateral sural nerve graft on recovery of potency and continence
      following radical prostatectomy: 3-year longitudinal study.
AB  - PURPOSE: We conducted a 3-year longitudinal study assessing the impact of
      unilateral sural nerve graft on recovery of potency and continence following
      radical prostatectomy. MATERIALS AND METHODS: A total of 113 patients undergoing
      radical retropubic prostatectomy were classified into 3 groups according to the
      degree of nerve sparing, that is unilateral nerve preservation with contralateral
      sural nerve graft interposition, bilateral nerve sparing and unilateral nerve
      sparing. Urinary continence and potency were estimated by the UCLA Prostate
      Cancer Index questionnaire. RESULTS: Patients in the nerve sparing plus sural
      nerve graft group were younger than those in the bilateral nerve sparing or
      unilateral nerve sparing groups. At baseline the unilateral nerve sparing plus
      sural nerve graft group and the bilateral nerve sparing group reported better
      sexual function than the unilateral nerve sparing group (62.1 and 61.5 vs 49.9,
      p<0.05). The bilateral nerve sparing group showed more rapid recovery than the
      unilateral nerve sparing plus sural nerve graft group after radical retropubic
      prostatectomy (p<0.01). After 24 months there were no significant differences
      observed between the bilateral nerve sparing and the unilateral nerve sparing
      plus sural nerve graft group (28.7 vs 32.9). The bilateral nerve sparing group
      reported a better sexual function score than the unilateral nerve sparing group
      throughout the postoperative period (p<0.05). The bilateral nerve sparing group
      maintained significantly better urinary function at 1 month after radical
      retropubic prostatectomy than the unilateral nerve sparing plus sural nerve graft
      group (p <0.05). After 3 months these groups were almost continent. The
      unilateral nerve sparing group reported lower urinary function scores during the
      first year compared to the other groups. CONCLUSIONS: The nerve graft procedure
      may contribute to the recovery of urinary function as well as sexual function
      after radical retropubic prostatectomy. This finding needs to be validated in a
      randomized trial.

PMID- 17499798
TI  - Management of high grade renal trauma: 20-year experience at a pediatric level I
      trauma center.
AB  - PURPOSE: In the last 20 years the management of high grade, blunt renal trauma at
      our institution has evolved from primarily an operative approach to an expectant
      nonoperative approach. To evaluate our experience with the expectant nonoperative
      management of high grade, blunt renal trauma in children, we reviewed our 20-year
      experience regarding evaluation, management and outcomes in patients treated at
      our institution. MATERIALS AND METHODS: We retrospectively studied all patients
      sustaining renal trauma between 1983 and 2003. Medical records were reviewed for
      mechanism of injury, assigned grade of renal injury, patient treatment,
      indications for and timing of surgery, and outcome. Injuries were categorized as
      either low grade (I to III) or high grade (IV to V). RESULTS: We reviewed the
      medical records of 164 consecutive children who sustained blunt renal trauma
      between 1983 and 2003. A total of 38 patients were excluded for inadequate
      information. Of the remaining 126 children 60% had low grade and 40% had high
      grade renal injuries. A total of 11 patients (8.7%) required surgical or
      endoscopic intervention for renal causes, including 2 for congenital renal
      abnormalities and 1 for clot retention. Eight patients (6.3%) required surgical
      intervention for isolated renal trauma, of whom 2 (1.6%) required immediate
      surgical intervention for hemodynamic instability and 6 (4.8%) were treated with
      a delayed retroperitoneal approach. Only 4 patients (3.2%) required nephrectomy.
      All patients receiving operative intervention had high grade renal injury.
      CONCLUSIONS: Initial nonsurgical management of high grade blunt renal trauma in
      children is effective and is recommended for the hemodynamically stable child.
      When a child has persistent symptomatic urinary extravasation delayed
      retroperitoneal drainage may become necessary to reduce morbidity. Minimally
      invasive techniques should be considered before open operative intervention.
      Early operative management is rarely indicated for an isolated renal injury,
      except in the child who is hemodynamically unstable.

PMID- 17499799
TI  - The effects of long-term administration of oral desmopressin on the baseline
      secretion of antidiuretic hormone and serum sodium concentration for the
      treatment of nocturia: a circadian study.
AB  - PURPOSE: We assessed the effects of long-term oral desmopressin on serum sodium
      and baseline antidiuretic hormone secretion in elderly patients with nocturia.
      MATERIALS AND METHODS: A total of 15 elderly male patients with severe nocturia
      (greater than 3 voids nightly) who did not show hyponatremia within 7 days of
      administration of 0.2 mg desmopressin were enrolled in this study. Desmopressin
      (0.2 mg) was administered orally nightly for 1 year. Before and 1 month after the
      1-year medication 24-hour circadian studies were performed to monitor changes in
      antidiuretic hormone. Every 3 months during the 1-year medication serum changes
      and timed urine chemistry were monitored. RESULTS: Desmopressin significantly
      decreased nocturnal urine output and the number of nocturia episodes (p<0.01).
      Compared to before treatment desmopressin gradually decreased serum sodium and
      induced statistically but not clinically significant hyponatremia after 6 months
      of treatment. After discontinuing desmopressin serum sodium returned to the
      normal range in all patients. There were no significant differences when baseline
      and posttreatment endogenous antidiuretic hormone were compared. No serious
      systemic complications were found during medication. CONCLUSIONS: Long-term
      desmopressin administration gradually decreased the serum concentration and
      induced significant hyponatremia from 6 months in patients who did not show
      initial hyponatremia. Long-term administration of desmopressin for 1 year in
      elderly patients did not affect baseline antidiuretic hormone secretion. For long
      term desmopressin administration serum sodium should be assessed regularly, at
      least every 6 months.

PMID- 17499801
TI  - Targeting beta2-microglobulin mediated signaling as a novel therapeutic approach
      for human renal cell carcinoma.
AB  - PURPOSE: We previously reported that the biological functions of beta2
      microglobulin include antigen presentation and oncogenic activity. In the current
      study we investigated the direct role of beta2-microglobulin in the regulation of
      human renal cell carcinoma cell growth and the possible apoptotic inducing effect
      of blocking the beta2-microglobulin signaling pathway using an anti-beta2
      microglobulin neutralizing antibody. MATERIALS AND METHODS: We examined the
      effects of recombinant beta2-microglobulin protein and anti-beta2-microglobulin
      antibody on renal cell carcinoma cell growth and apoptosis in vitro. To seek a
      molecular understanding of anti-beta2-microglobulin antibody induced apoptosis we
      analyzed alterations in the growth and survival signaling components in the
      phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase and c
      jun N-terminal kinase mediated pathways using corresponding kinase inhibitors in
      SN12C cells. RESULTS: Recombinant beta2-microglobulin protein increased the
      growth of the 3 human renal cell carcinoma cell lines SN12C, Caki-1 and ACHN in a
      dose and time dependent manner. Treatment of SN12C, Caki-1 and ACHN cells with an
      anti-beta2-microglobulin polyclonal antibody strongly suppressed the growth of
      these cells in vitro, also in a dose and time dependent manner. The addition of
      recombinant beta2-microglobulin protein or anti-beta2-microglobulin antibody
      increased or decreased, respectively, the anchorage independent growth of SN12C
      cells. The recombinant beta2-microglobulin protein accelerated cell growth via
      activating phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated
      kinase, and induced the phosphorylation of Bcl-xL/Bcl-2-associated death
      promoter. However, treatment with anti-beta2-microglobulin antibody induced cell
      death by inhibiting the phosphorylation of Akt and extracellular signal-regulated
      kinase, and activating c-jun N-terminal kinase, resulting in the induction of
      phosphorylation of B-cell lymphoma 2 and decreased phosphorylation of Bcl-xL/Bcl
      2-associated death promoter, leading to apoptosis. CONCLUSIONS: Our results
      demonstrate that beta2-microglobulin has an important role in regulating the
      growth and survival of renal cell carcinoma cells and anti-beta2-microglobulin
      antibody offers a potential novel therapy for the treatment of human renal cell
      carcinoma.

PMID- 17499802
TI  - Interstitial photodynamic therapy of the canine prostate using intra-arterial
      administration of photosensitizer and computerized pulsed light delivery.
AB  - PURPOSE: We determined the feasibility of complete treatment of the canine
      prostate and long-term effectiveness of interstitial photodynamic therapy using
      the intra-arterial photosensitizer QLT0074 (benzoporphyrin derivative 1,3-diene
      C,D-diethylene glycol ester A ring) (QLT, Vancouver, British Columbia, Canada)
      administration and pulsed light delivery. MATERIALS AND METHODS: The prostate
      gland of 11 dogs were infused with QLT0074 via the prostatovesical arteries (2 mg
      drug per artery bilaterally) under fluoroscopic guidance. Immediately following
      infusion the prostate was surgically exposed and 7 optical fibers with 1.5 cm
      cylindrical diffusers in after loading sheaths were inserted into the prostate
      through a template. Light was delivered sequentially to the optic fibers via a
      computer driven switch system. One dog was sacrificed 6 days after photodynamic
      therapy to assess acute tissue effects. The other 10 dogs were monitored for
      clinical tolerance and urinary function, and sacrificed at between 3 and 11
      months. Prostate specimens were examined microscopically to evaluate long-term
      tissue reactions. RESULTS: Comprehensive destruction of the prostate was noted in
      the acute dog. Except for urinary retention and mild hematuria no other
      perioperative complications were observed in the chronic dogs. Urodynamic
      examination did not reveal deleterious bladder and urethral function. Average
      prostate volume decreased 71% at 3 months and 56% after 6 months (p=0.007 and
      0.014, respectively). Microscopic evaluation revealed prostate glandular
      epithelial atrophy, stromal fibrosis and mononuclear cell infiltration.
      CONCLUSIONS: Interstitial photodynamic therapy using intra-arterial QLT0074 and
      pulsed light delivery is safe and feasible for comprehensive destruction of the
      canine prostate. Clinical trials are required to confirm it for managing prostate
      diseases.

PMID- 17499803
TI  - Single trocar laparoscopic nephrectomy using magnetic anchoring and guidance
      system in the porcine model.
AB  - PURPOSE: We assessed the feasibility of single keyhole laparoscopic surgery using
      a novel transabdominal magnetic anchoring and guidance system platform in the
      porcine model. MATERIALS AND METHODS: A collaborative research group was formed
      to build a prototype system of magnetically anchored instruments for trocar-free
      laparoscopy. The design mandate was that the developed technology should be able
      to deploy into the insufflated abdomen through an existing 12 mm diameter trocar
      and then be moved into position in the peritoneum by manipulating external
      magnets. The magnetic anchoring and guidance system concept was advanced to a
      working prototype with a system of external magnetic anchors, an internal camera
      system and a hook cautery supported by an intra-abdominal robotic arm. This
      prototype system was then evaluated in vivo in a porcine laparoscopic nephrectomy
      model. RESULTS: Two nonsurvival porcine laparoscopic nephrectomies were
      successfully completed without complications via a single 15 mm transumbilical
      trocar using the prototype magnetic anchoring and guidance system camera and the
      magnetically anchored robotic arm cauterizer. A conventional laparoscopic grasper
      was used for retraction through the 15 mm trocar after magnetic anchoring and
      guidance system deployment. The renal artery and vein were transected with a
      conventional Endo-GIA stapler introduced through the 15 mm trocar. Procedure time
      was not recorded and blood loss was minimal. CONCLUSIONS: Single trocar
      laparoscopic nephrectomy using magnetically anchored instrumentation is
      technically feasible, demonstrating that intracorporeal instrument manipulation
      may overcome the limitations of current laparoscopic and robotic surgery by
      allowing unhindered intra-abdominal movement. This single access technique may be
      used with natural orifice surgery approaches and it has the potential to realize
      incision-free intra-abdominal surgery.

PMID- 17499804
TI  - Kidney folding: the Y-plasty--a means of creating a dependent ureteropelvic
      junction in the child with giant hydronephrosis.
AB  - PURPOSE: Occasionally, in the presence of severe dilatation and parenchymal
      thinning, postoperative obstruction or stasis may secondarily occur even after
      creation of a funneled ureteropelvic junction. Preferential filling of a severely
      dilated lower pole may kink or distort the ureteropelvic junction, causing this
      problem. MATERIALS AND METHODS: A requirement for renal folding is a large
      hydronephrotic kidney with severe mid renal parenchymal thinning. After
      pyeloplasty if it is apparent that secondary obstruction is a possibility, and
      simple lateral or posterior fixation of the lower pole to retroperitoneal fascia
      will not resolve the problem, the lower pole can be brought superiorly adjacent
      to the upper pole and fixed in position with 2 or 3, 2-zero or 3-zero polyglactin
      sutures, creating a "Y" configuration with the ureteropelvic junction dependent
      from all calices. We reviewed the records of 5 children who underwent this
      procedure. RESULTS: Five patients with severe upper tract dilatation were treated
      successfully. Four underwent primary pyeloplasty with concomitant renal folding,
      and 1 had persistent hydronephrosis with recurrent pyonephrosis before undergoing
      this procedure secondarily. All patients achieved excellent results with normal
      drainage postoperatively. CONCLUSIONS: Renal folding is a simple surgical
      maneuver that can be applied easily and successfully when the situation warrants.
      It allows creation of a dependent, funneled ureteropelvic junction in the
      presence of giant hydronephrosis.

PMID- 17499806
TI  - Relationship between the integrity of the pelvic floor muscles and early recovery
      of continence after radical prostatectomy.
AB  - PURPOSE: We investigated how the preoperatively estimated integrity of pelvic
      floor muscles related to the recovery of continence after radical prostatectomy.
      MATERIALS AND METHODS: A total of 94 patients underwent magnetic resonance image
      of the prostate and urodynamic studies before undergoing radical prostatectomy
      and evaluation of voiding symptoms before, and 3 and 6 months after surgery.
      Incontinence was defined as any unwanted urine leakage. On the magnetic resonance
      image the thickness of the levator ani and pelvic diaphragm, and prostate volume
      were measured to correlate with continence status. RESULTS: Incontinence was
      noted in 41.5% and 15.9% of the patients at 3 and 6 months, respectively.
      Recovery of continence 3 months after RP was related to the thickness of the
      pelvic diaphragm on sagittal imaging (p=0.017), the ratio of the levator ani on
      the axial image to prostate volume (p=0.047), functional urethral length
      (p=0.007) and incontinence before surgery (p=0.009). Recovery at 6 months was
      related to neurovascular bundle sparing (p=0.013) and marginally to the pelvic
      diaphragm on sagittal imaging (p=0.059). On multivariate analysis the pelvic
      diaphragm on sagittal imaging (HR 2.455, 95% CI 0.894-6.739, p=0.008) and the
      ratio of the levator ani on the axial image to prostate volume (HR 1.886, 95% CI
      0.952-3.736, p=0.011) significantly predicted continence at 3 months, while at 6
      months only the pelvic diaphragm on sagittal imaging showed a significant
      relationship (p=0.024). CONCLUSIONS: Pelvic diaphragm thickness and the ratio of
      levator ani thickness to prostate volume are independent factors predictive of
      post-prostatectomy incontinence. Patients with better developed pelvic floor
      muscles, especially in relation to the size of the prostate, can be expected to
      achieve earlier recovery of continence after radical prostatectomy.

PMID- 17499807
TI  - Ejaculatory disorders may affect screening for prostate cancer.
AB  - PURPOSE: Ejaculatory disorders will be experienced in most men who are treated
      for localized prostate cancer. Baseline rates of ejaculatory disorders are
      unknown in men at risk for prostate cancer. Therefore, we explored the prevalence
      of those disorders and associated bother in men without evidence of prostate
      cancer who participated in an annual prostate cancer screening event. MATERIALS
      AND METHODS: A cohort of 1,273 men without clinical evidence of prostate cancer
      completed the self-administered Danish Prostate Symptom Score for sexual
      dysfunction. This questionnaire quantifies the rate of reduced ejaculatory
      volume, ejaculatory pain and the rate of coexistent erectile dysfunction.
      RESULTS: Mean age was 57.6 years (range 40 to 89). Of all men 46% (563) had
      reduced ejaculatory volume and 66% (356) of affected men were bothered by this
      condition. Ejaculatory pain was reported in 11% (134) and 89% (118) of these men
      reported associated bother. Finally, 45% (554) reported erectile dysfunction and
      73% (403) reported associated bother. Reduced ejaculatory volume was associated
      with erectile dysfunction (p<0.001) and advanced age (p<0.001). Ejaculatory pain
      was not associated with one of these variables. CONCLUSIONS: Virtually all men
      will be affected by ejaculatory disorders after definitive treatment for
      localized prostate cancer. Therefore, it is important to observe that half of
      these individuals already have underlying reduced ejaculatory volume before
      treatment. Moreover, 1 of 10 men will be affected by ejaculatory pain. Both
      disorders are a significant source of bother and should be considered when
      treatment related quality of life is assessed.

PMID- 17499809
TI  - The volume at which women leak first on urodynamic testing is not associated with
      quality of life, measures of urethral integrity or surgical failure.
AB  - PURPOSE: We determined if the bladder volume at which urodynamic stress
      incontinence is first detected is related to preoperative quality of life,
      urethral sphincter assessment or surgical outcome in women undergoing continence
      surgery. MATERIALS AND METHODS: Charts of consecutive women who underwent a sling
      or Burch procedure were reviewed. Preoperative and postoperative assessment
      included the Incontinence Impact Questionnaire and Urogenital Distress Inventory.
      Urodynamic stress incontinence volume is the bladder volume at which urodynamic
      stress incontinence was first detected. Women were divided into 4 groups
      according to urodynamic stress incontinence volume, and compared with respect to
      maximum urethral closure pressure, Valsalva leak point pressure, Incontinence
      Impact Questionnaire and Urogenital Distress Inventory. Urodynamic stress
      incontinence persistence was evaluated only in patients who had sling surgery.
      RESULTS: A total of 168 women were recruited for the study. Urodynamic stress
      incontinence volume was 100 ml for 31% of women, 200 ml for 17%, 300 ml for 17%
      and 400 ml or greater for 35%. Baseline and postoperative Urogenital Distress
      Inventory, Incontinence Impact Questionnaire, maximal urethral closure pressure
      and Valsalva leak point pressure did not differ by urodynamic stress incontinence
      volume. Among the 116 patients who had the sling procedure, urodynamic stress
      incontinence persistence did not differ by urodynamic stress incontinence volume
      (p=0.72). CONCLUSIONS: Women who demonstrate urodynamic stress incontinence at
      lower bladder volumes do not report greater bother from incontinence than women
      who leak at higher volumes, suggesting leakage severity on urodynamics is not an
      adequate reflection of incontinence related quality of life.

PMID- 17499810
TI  - Effects of (-)-epigallocatechin-3-gallate in Ca2+ -permeable non-selective cation
      channels and voltage-operated Ca2+ channels in vascular smooth muscle cells.
AB  - The effects of (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin
      of tea, on Ca(2+)-permeable non-selective cation currents (NSCC) and voltage
      operated Ca(2+) channels (VOCC) have been investigated in cultured rat aortic
      smooth muscle cells using the whole-cell voltage-clamp technique. Under the
      Cs(+)/tetraethylammonium (TEA)-containing internal solution, and in the presence
      of nifedipine (1 microM), EGCG (30 microM) activated a long-lasting inward
      current, with a reversal potential (E(rev)) of approximately 0 mV. This current
      was not significantly altered by the replacement of [Cl(-)](i) or [Cl(-)](o),
      implying that the inward current was not a chloride channel, but a NSCC. SKF
      96365 (30 microM) and Cd(2+) (500 microM) almost completely abolished the EGCG
      induced NSCC. A higher dose of EGCG (100 microM) additionally activated a
      nifedipine-sensitive inward current in the absence of depolarization protocol.
      EGCG (100 microM) also potentiated a nifedipine-sensitive voltage-dependent
      Ba(2+)-current during the first 5 min of incubation. However, after > 10 min of
      incubation with EGCG, this current was significantly inhibited. Our results
      suggest that EGCG caused a Ca(2+) influx into smooth muscle cells via VOCC
      (probably L-type) and other SKF-96365- and Cd(2+)-sensitive Ca(2+)-permeable
      channels. The action described here may be responsible for the contraction
      induced by EGCG in rat aortic rings and for the rise of the intracellular
      concentration of Ca(2+) in rat aortic smooth muscle cells evoked by this
      catechin. On the other hand, the inhibition of VOCC after > 10 min of incubation
      may be, in part, responsible for the relaxation of rat aorta induced by EGCG.

PMID- 17499811
TI  - Modulation of aortic vascular reactivity by sex hormones in a male rat model of
      metabolic syndrome.
AB  - Modulation by sex hormones of aortic reactivity in rats with the metabolic
      syndrome (MS) was investigated. The following groups of weanling male Wistar rats
      were used: control rats (C) received regular tap water while MS rats received 30%
      sucrose in their drinking water; both had rodent chow for 24 weeks. These two
      groups were further subdivided into the following four groups: intact (Int),
      castrated (Cas), castrated plus testosterone (T) and castrated plus estradiol
      (E). Vascular response of thoracic aortic rings to norepinephrine (NE),
      acetylcholine (ACh), indomethacin (Indo) and nitro-l-arginine-methyl ester (L
      NAME) was investigated. Blood pressure (BP) and serum nitrates and nitrites were
      measured. BP and serum nitrates and nitrites were modified by castration and
      treatments with either T or E. Vasoconstriction in Int MS and Cas MS+T aortas was
      larger than in C and Cas C+T, respectively. Vasodilation in Int MS and Cas MS+T
      was reduced in comparison with C and Cas C+T, Cas MS and Cas MS+E. Indomethacin
      decreased vasoconstriction in all groups (P<0.002) but Int C and Cas C+T remained
      significantly smaller than Int MS and Cas MS+T. l-NAME in NE-contracted vessels
      induced a significant increase in vasoconstriction, except in Cas C+E rats; the
      responses of Int MS and Cas MS+T were significantly larger than in Int C and Cas
      C+T. The results suggest endothelial dysfunction in Int MS and Cas MS+T and a
      protective effect resulting from castration and castration plus E in MS animals,
      indicating a sex hormone influence.

PMID- 17499812
TI  - Theaflavins induced apoptosis of LNCaP cells is mediated through induction of
      p53, down-regulation of NF-kappa B and mitogen-activated protein kinases
      pathways.
AB  - Prostate cancer (PCA), the most frequently diagnosed malignancy in men,
      represents an excellent candidate disease for chemoprevention studies because of
      its particularly long latency period, high rate of mortality and morbidity.
      Infusion of black tea and its polyphenolic constituents have been shown to
      possess antineoplastic effects in androgen dependent PCA in both in vivo and in
      vitro models including transgenic animals. In the present study, we report that
      black tea polyphenol, Theaflavins (TF)-induced apoptosis in human prostate
      carcinoma, LNCaP cells is mediated via modulation of two related pathways: up
      regulation of p53 and down-regulation of NF-kappa B activity, causing a change in
      the ratio of pro-and antiapoptotic proteins leading to apoptosis. The altered
      expression of Bcl-2 family member proteins triggered the release of cytochrome-C
      and activation of initiator capsase 9 followed by activation of effector caspase
      3. Furthermore, TF also affected the protein expression of mitogen activated
      protein kinases (MAPK) pathways. Our results demonstrated that TF treatment
      resulted in down-regulation of phospho-extracellular signal-regulated protein
      kinase (Erk1/2) and phospho-p38 MAPK expressions. We conclude that TF induces
      apoptosis in LNCaP cells by shifting the balance between pro-and antiapoptotic
      proteins and down-regulation of cell survival pathways leading to apoptosis.
      Further extending this work, we also showed that TF induces apoptosis in androgen
      independent PCA cell line, PC-3 through caspases and MAPKs mediated pathways.
      Thus, effect of TF on PCA cell lines seems to be irrespective of their androgen
      status.

PMID- 17499813
TI  - The digitalis-like steroid hormones: new mechanisms of action and biological
      significance.
AB  - Digitalis-like compounds (DLC) are a family of steroid hormones synthesized in
      and released from the adrenal gland. DLC, the structure of which resembles that
      of plant cardiac glycosides, bind to and inhibit the activity of the ubiquitous
      cell surface enzyme Na(+), K(+)-ATPase. However, there is a large body of
      evidence suggesting that the regulation of ion transport by Na(+), K(+)-ATPase is
      not the only physiological role of DLC. The binding of DLC to Na(+), K(+)-ATPase
      induces the activation of various signal transduction cascades that activate
      changes in intracellular Ca(++) homeostasis, and in specific gene expression.
      These, in turn, stimulate endocytosis and affect cell growth and proliferation.
      At the systemic level, DLC were shown to be involved in the regulation of major
      physiological parameters including water and salt homeostasis, cardiac
      contractility and rhythm, systemic blood pressure and behavior. Furthermore, the
      DLC system has been implicated in several pathological conditions, including
      cardiac arrhythmias, hypertension, cancer and depressive disorders. This review
      evaluates the evidence for the different aspects of DLC action and delineates
      open questions in the field.

PMID- 17499814
TI  - The use of chemical dispersants to combat oil spills at sea: A review of practice
      and research needs in Europe.
AB  - In order to better understand the practice of dispersant use, a review has been
      undertaken of marine oil spills over a 10 year period (1995-2005), looking in
      particular at variations between different regions and oil-types. This viewpoint
      presents and analyses the review data and examines a range of dispersant use
      policies. The paper also discusses the need for a reasoned approach to dispersant
      use and introduces past cases and studies to highlight lessons learned over the
      past ten years, focussing on dispersant effectiveness and monitoring; toxicity
      and environmental effects; the use of dispersants in low salinity waters;
      response planning and future research needs.

PMID- 17499815
TI  - [Brainstem cavernomas: surgical experience at the CH Sainte-Anne general
      hospital].
AB  - BACKGROUND AND PURPOSE: No standard treatment for brainstem cavernoma has been
      established because of the lack of sufficient data about the natural history of
      these lesions in a highly functional location with potential difficult surgical
      accessibility. METHODS: We present a series of 82 brainstem cavernomas managed at
      the Sainte-Anne Hospital. Surgery was undertaken for 25 with stereotactic biopsy
      for 9 and direct surgery for 19 (3 after biopsy). RESULTS: Surgical outcome was
      good or fair for 17 patients. Two patients worsened and one died. Biopsy results
      were disappointing with high morbidity (4 patients with 2 permanent deficits).
      Histological diagnostic was possible for all biopsies. CONCLUSION: In light of
      these results, an active surgical attitude could be proposed for cavernomas in an
      accessible locations which have produced at least one previous hemorrhage.
      Stereotactic biopsies for suspect brainstem cavernoma must be avoided.

PMID- 17499816
TI  - [Cavernomas of the central nervous system. Historical data and changing ideas].
AB  - Since the advent of modern neuroimaging (MRI) cerebral cavernomas are usually
      diagnosed "in vivo". In this paper we describe the data which improved our
      knowledge of the disease: 1) nosologically, cerebral cavernomas belong to the
      group of cerebral vascular hamartomas which can be associated between themselves
      ("mixed" lesions); 2) hemodynamically, the annual risk of hemorrhage increases
      after a first bleeding and in deep located lesions (brainstem); 3) association
      between cavernomas and developmental venous anomalies may be observed; the later
      on must be left in place at operation; 4) immunocytochemical studies (PCNA) show
      that cavernomas should be considered more as a benign vascular tumor than as a
      malformation; 5) familial forms (20%) are characterized by multiple locations and
      "de novo" lesions; 6) better understanding of the natural history of cavernomas,
      which is a dynamic lesion, leads to broader surgical indications (no alternative
      treatment).

PMID- 17499817
TI  - Experience-dependent changes in NMDA receptor composition at mature central
      synapses.
AB  - N-methyl-D-aspartate receptor (NMDAR) activation is obligatory for the induction
      of diverse forms of synaptic plasticity. The molecular composition and the
      function of NMDARs are themselves modified by synaptic activity, which, in turn,
      alters the ability of synapses to undergo subsequent plastic modification. This
      homeostatic control of synaptic plasticity is well-known for the experience
      dependent development of sensory cortices. However, it is now becoming clear that
      NMDAR properties may not only be altered at juvenile, but also at mature
      synapses. Diverse types of behavioral manipulation, such as sensory experience,
      learning and sleep deprivation alter the NR2A/NR2B ratio of hippocampal or
      cortical NMDARs. As an additional facet to the dynamics of NMDAR function, NMDAR
      trafficking is regulated by G-protein-coupled neurotransmitter receptors
      implicated in learning and arousal, such as orexin and dopamine. These findings
      suggest that mature glutamatergic synapses may be modified by recent activity via
      alterations in synaptic NMDAR function. Rapid forms of NMDAR trafficking, perhaps
      controlled by the neurochemical environment featuring specific states of arousal
      and learning, may regulate plasticity and modulate cognitive abilities in
      adulthood.

PMID- 17499818
TI  - A meta-analytic review of category naming in Alzheimer's disease.
AB  - Patients with Alzheimer's disease (AD) experience word-finding difficulties that
      become increasingly pronounced as pathological changes accrue in the brain. One
      question that has received increasing attention over the last two decades
      concerns whether the anomia in AD is category-specific, i.e. differentially
      affects the ability to name living things (LT) and non-living things (NLT). The
      current meta-analysis systematically reviewed the effect sizes for naming
      pictures of LT and NLT in comparisons of AD patients and healthy controls in 21
      studies with over 1000 participants (557 patients and 509 healthy controls). A
      random effects model analysis revealed no significant difference in the large
      weighted effect sizes for naming pictures of LT and NLT (d=1.76 and 1.49,
      respectively). Moderator variable analyses revealed a significant impact of
      stimulus colour on the effect size for LT, indicating that using colour stimuli
      significantly increases the impairment of naming LT in AD patients. Additionally,
      we found that LT and the NLT effect sizes were larger for samples with
      proportionally more female patients; smaller samples produced larger LT effect
      sizes. In contrast, effect sizes were not significantly related to dementia
      severity, patient age, the number of stimuli, years of education, or the number
      of matching variables controlled.

PMID- 17499819
TI  - Direct intracranial recording of body-selective responses in human extrastriate
      visual cortex.
AB  - We recorded intracranial local field potentials (iLFPs) in right extrastriate
      visual cortex of a patient prior to surgery for epilepsy. Visual evoked
      potentials revealed a highly selective response to images of bodies, relative to
      faces, mammals, and tools, which was restricted to a focal region in the lateral
      occipitotemporal cortex that corresponds to the location of the extrastriate body
      area (EBA). Body-selective activity started around 190 ms and peaked 260 ms post
      stimulus onset. These findings provide the first direct electrophysiological
      evidence for an early visual processing stage in human lateral occipitotemporal
      cortex that is specialized for processing human body shapes.

PMID- 17499820
TI  - The time course of hemispheric differences in categorical and coordinate spatial
      processing.
AB  - Spatial relations between objects can be represented either categorically or
      coordinately. The metric, coordinate representation is associated with
      predominant right hemisphere activity, while the abstract, qualitative
      categorical representation is thought to be processed more in the left hemisphere
      [Kosslyn, S. M. (1987). Seeing and imagining in the cerebral hemispheres: A
      computational analysis. Psychological Review, 94, 148-175]. This hypothesized
      lateralization effect has been found in a number of studies, along with
      indications that specific task demands can be crucial for these outcomes. In the
      current experiment a new visual half field task was used which explores these
      hemispheric differences and their time course by means of a match-to-sample
      design. Within retention intervals that were brief (500 ms), intermediate (2000
      ms), or long (5000 ms), the processing of categorical and coordinate
      representations was studied. In the 500 ms interval, the hemispheric effect
      suggested by Kosslyn (1987) was found, but in the longer intervals it was absent.
      This pattern of the lateralization effect is proposed to be caused by the
      differential effect the retention interval has on coordinate and categorical
      representations. Coordinate spatial relations appear susceptible to changes in
      retention interval and decay very quickly over time, congruent with previous
      findings about accurate location memory. The processing of categorical spatial
      relations showed less decay and only between 2000 ms and 5000 ms. Qualitative
      self reports suggest that the decay found for categorical relations might be
      caused by a switch from a visual to a more verbal memorization strategy.

PMID- 17499821
TI  - Age increases vulnerability to bacterial endotoxin-induced behavioral decrements.
AB  - Peripheral lipopolysaccharide (LPS) or proinflammatory cytokines produce
      alterations in learning, memory, and other behaviors. Additionally, research has
      demonstrated that factors such as dose, route of administration, species, strain,
      gender, and age are important modulatory factors in the effects of endotoxin
      exposure. Previous research from our laboratory and others indicate that LPS
      induced behavioral deficits are greater in older subjects. The current study
      examined avoidance learning in a negatively reinforced operant procedure (i.e.,
      two-way active avoidance conditioning) following single or repeated
      intraperitoneal LPS injections in 2- and 12-month-old male C57BL/6J mice. LPS
      treated subjects show impaired acquisition of the task regardless of the age of
      the subject, as these animals performed significantly fewer avoidance responses
      than controls. However, the effects of LPS administration were more pronounced in
      the 12-month-old animals, particularly for the subjects given repeated LPS
      injections. These results support the hypothesis that endotoxin exposure is
      capable of altering performance in this task in a way that may reflect deficits
      in learning, and provide evidence that increased age may exacerbate these
      deleterious behavioral effects.

PMID- 17499822
TI  - Molecular cloning and biochemical characterization of indole-3-acetic acid
      methyltransferase from poplar.
AB  - Indole-3-acetic acid (IAA) is the most active endogenous auxin and is involved in
      various physiological processes in higher plants. Concentrations of IAA in plant
      tissues are regulated at multiple levels including de novo biosynthesis,
      conjugation/deconjugation, and degradation. In this paper, we report molecular
      isolation and biochemical characterization of a gene PtIAMT1 from poplar encoding
      IAA methyltransferase (IAMT), which plays a role in regulating IAA homeostasis.
      PtIAMT1 was identified from the poplar genome based on sequence similarity to
      Arabidopsis IAMT. A full-length cDNA of PtIAMT1 was cloned from poplar roots via
      RT-PCR. Recombinant PtIAMT1 expressed in Escherichia coli was purified to
      electrophoretic homogeneity. Enzyme assays combined with GC-MS verified that
      PtIAMT1 catalyzes formation of methyl indole-3-acetate using S-adenosyl-l
      methionine (SAM) as a methyl donor and IAA as a methyl acceptor. PtIAMT1 had a
      temperature optimum at 25 degrees C and a pH optimum at pH 7.5. Its activity was
      promoted by K(+) but inhibited by Fe(2+), Cu(2+) and Zn(2+). Under steady-state
      conditions, PtIAMT1 exhibited apparent K(m) values of 23.1 microM and 30.4 microM
      for IAA and SAM, respectively. Gene expression analysis showed that PtIAMT1 had
      the highest level of expression in stems, a moderate level of expression in young
      leaves, and a low level of expression in roots. Presence of PtIAMT1 transcripts
      in several organs suggests that PtIAMT1 is involved in development of multiple
      organs in poplar.

PMID- 17499823
TI  - Anthraquinones from the stem bark of Stereospermum zenkeri with antimicrobial
      activity.
AB  - Two anthraquinones, zenkequinones A and B were isolated from the stem bark of
      Stereospermum zenkeri together with known sterequinone-F, p-coumaric acid,
      sitosterol-3-O-beta-D-glucopyranoside and 3beta-hydroxyolean-12-en-28-O-beta-D
      glucopyranoside. Their structures were established by spectroscopic methods. The
      antimicrobial activity of the isolated compounds was evaluated against six
      multiresistant strains of pathogens. Zenkequinone B showed the best antibacterial
      activity (MIC 9.50 microg/ml) against gram-negative Pseudomonas aeruginosa.

PMID- 17499824
TI  - Serine racemases from barley, Hordeum vulgare L., and other plant species
      represent a distinct eukaryotic group: gene cloning and recombinant protein
      characterization.
AB  - Several d-amino acids have been identified in plants. However, the biosynthetic
      pathway to them is unclear. In this study, we cloned and sequenced a cDNA
      encoding a serine racemase from barley which contained an open reading frame
      encoding 337 amino acid residues. The deduced amino acid sequence showed
      significant identity to plant and mammalian serine racemases and contained
      conserved pyridoxal 5-phosphate (PLP)-binding lysine and PLP-interacting amino
      acid residues. The purified gene product catalyzed not only racemization of
      serine but also dehydration of serine to pyruvate. The enzyme requires PLP and
      divalent cations such as Ca(2+), Mg(2+), or Mn(2+), but not ATP, whereas
      mammalian serine racemase activity is increased by ATP. In addition to the
      results regarding the effect of ATP on enzyme activity and the phylogenetic
      analysis of eukaryotic serine racemases, the antiserum against Arabidopsis serine
      racemase did not form a precipitate with barley and rice serine racemases. This
      suggests that plant serine racemases represent a distinct group in the eukaryotic
      serine racemase family and can be clustered into monocot and dicot types.

PMID- 17499825
TI  - Network flux analysis: impact of 13C-substrates on metabolism in Arabidopsis
      thaliana cell suspension cultures.
AB  - The aim of this study was to test the assumption that (13)C-enrichment of
      respiratory substrate does not perturb metabolism. Cell suspension cultures of
      Arabidopsis thaliana were grown in MS medium containing unlabelled glucose (with
      (13)C at natural abundance), 100% [1-(13)C]glucose, 100% [U-(13)C(6)]glucose or
      10% [U-(13)C(6)]glucose plus 90% unlabelled glucose. There was no significant
      difference in the metabolism of [U-(14)C]glucose between the cultures. Similarly,
      the pattern of (14)CO(2) release from specifically labelled [(14)C]-substrates
      was unaffected. Principal component analysis of (13)C-decoupled (1)H NMR
      metabolite fingerprints of cell extracts was unable to discriminate between the
      different culture conditions. It is concluded that (13)C-enrichment of the growth
      substrate has no effect on flux through the central pathways of carbon metabolism
      in higher plants. This conclusion supports the implicit assumption in metabolic
      flux analysis that steady-state (13)C-labelling does not perturb fluxes through
      the reactions of the metabolic network it seeks to quantify.

PMID- 17499826
TI  - Cutaneous leishmaniasis in southern Sri Lanka.
AB  - Cutaneous leishmaniasis is an established disease in Sri Lanka. The majority of
      cases have been reported from the North-Central Province, with the southern parts
      of the country considered less affected. However, during 2004, when the services
      of a dermatologist were available, a considerable number of patients were
      referred from the Southern Province, which formed the basis for this study. The
      clinical pattern, detailed geographical distribution within the Southern Province
      and periodicity of the cases were studied over a period of 12 months. Of the 113
      patients diagnosed, the highest number was within the 10-19 years age group. Most
      patients were from densely populated rural areas around Matara, a large town
      within this province. There was a notable increase in the number of cases
      presenting during February-March and August-September, which are periods
      following monsoonal rains. Exposed areas of the skin were commonly affected, with
      the majority of patients having single lesions. Females and males were equally
      affected. This is in contrast to our previous findings in the North-Central
      Province where the majority of patients were male soldiers with multiple lesions.

PMID- 17499827
TI  - Evidence of congenital transmission of Trypanosoma cruzi in a vector-free area of
      Bolivia.
AB  - A seroprevalence survey of Trypanosoma cruzi was carried out in two areas of
      South Bolivia. Triatoma infestans, the main vector of Tryp. cruzi, was abundant
      in the first area, but absent in the second one. Titration of Tryp. cruzi
      antibodies was carried out in children aged 6-24 months and their mothers. The
      seroprevalence of Chagas' disease was significantly higher in the area with the
      vector, but also high in the second area. Chagas' infection in children under 2
      years old could be linked to congenital transmission of parasites during
      pregnancy and/or delivery, despite active vector control in both areas.

PMID- 17499828
TI  - Validation of a reference ELISA for estrone glucuronide using urine samples
      normalized by dilution to a constant rate of urine production.
AB  - A direct enzyme linked immunosorbent assay (ELISA) system has been optimized as a
      reference method for the measurement of first statistically significant rises in
      estrone glucuronide excretion rates in human urine by analysing samples pre
      diluted at the time of the collection by the women subjects to a constant urine
      production rate of 150 mL/h. Validation was achieved by correlation of the
      individual menstrual cycle profiles with the corresponding estrone glucuronide
      excretion rates determined by radioimmunoassay (RIA) on the same urine samples
      for a total of 221 samples from nine cycles. The pre-dilution procedure removed
      random variations due to fluctuations in the daily rate of urine excretion and
      minimized between sample matrix effects. When the ELISA data were correlated with
      the RIA data, Deming regression gave a slope of 1.20+/-0.03 and an intercept of
      4.6+/-1.8 nmol/24h (r=0.944) and a random experimental error of 14.2 nmol/24h.
      The major difference in the measurements was a proportional error of 20%, which
      was present in either the ELISA or RIA methods or in both. Comparison of the
      standard normal variate transformation of the ELISA and RIA data gave hormonal
      profiles of the individual menstrual cycles (N=9) that overlapped almost
      perfectly. Statistically significant rises or falls in the magnitude of the
      excretion rate in one profile were mirrored faithfully in the other.

PMID- 17499829
TI  - On the relative fitness of early and late stage Simian immunodeficiency virus
      isolates.
AB  - Simian immunodeficiency virus (SIV) has been shown to evolve from a relatively
      slowly replicating and mildly cytopathic virus early in the infection (SIVMneCL8)
      to a faster replicating and more cytopathic virus at later stages of the
      infection (SIVMne170). It has recently been demonstrated that the early and
      mildly cytopathic variant SIVMneCL8 out-competed the late and highly cytopathic
      strain SIVMne170 in cell culture experiments, because the fitness disadvantage
      derived from the higher cytopathicity was not matched by a sufficient increase in
      the viral replication rate. However, in another set of experiments where the life
      span of cells in culture was artificially limited, the late and more cytopathic
      virus won the competition, because under this condition cytopahticity was not an
      important determinant of viral fitness. It was hypothesized that the limited life
      span experiment reflected the immune-mediated high turnover environment in vivo
      more accurately, and that the presence of immune responses accounts for the
      selection of the cytopathic strain SIVmne170 during later stages of the
      infection. This paper investigates the effect of immune responses, in particular
      cytotoxic T lymphocyte (CTL) responses, on the competition dynamics between these
      two SIV strains with the help of mathematical models. Model analysis and
      parameter estimates derived from previously published data on SIV growth kinetics
      suggest that the SIV-specific CTL response might not be the driving force that
      leads to the selection of the cytopathic strain SIVMne170 during later stages of
      the infection. This implies that more complex evolutionary mechanisms might have
      to be invoked in order to explain the emergence of these strains in vivo. One
      possibility is that the ability of multiple virus particles to infect the same
      cell (coinfection) might be a pre-requisite for the emergence of the cytopathic
      strain SIVMne170 as the disease progresses.

PMID- 17499830
TI  - Dietary chromium and nickel enhance UV-carcinogenesis in skin of hairless mice.
AB  - The skin cancer enhancing effect of chromium (in male mice) and nickel in UVR
      irradiated female Skh1 mice was investigated. The dietary vitamin E and
      selenomethionine were tested for prevention of chromium-enhanced skin
      carcinogenesis. The mice were exposed to UVR (1.0 kJ/m(2) 3 x weekly) for 26
      weeks either alone, or combined with 2.5 or 5.0 ppm potassium chromate, or with
      20, 100 or 500 ppm nickel chloride in drinking water. Vitamin E or
      selenomethionine was added to the lab chow for 29 weeks beginning 3 weeks before
      the start of UVR exposure. Both chromium and nickel significantly increased the
      UVR-induced skin cancer yield in mice. In male Skh1 mice, UVR alone induced 1.9+/
      0.4 cancers/mouse, and 2.5 or 5.0 ppm potassium chromate added to drinking water
      increased the yields to 5.9+/-0.8 and 8.6+/-0.9 cancers/mouse, respectively. In
      female Skh1 mice, UVR alone induced 1.7+/-0.4 cancers/mouse, and the addition of
      20, 100 or 500 ppm nickel chloride increased the yields to 2.8+/-0.9, 5.6+/-0.7
      and 4.2+/-1.0 cancers/mouse, respectively. Neither vitamin E nor selenomethionine
      reduced the cancer yield enhancement by chromium. These results confirm that
      chromium and nickel, while not good skin carcinogens per se, are enhancers of UVR
      induced skin cancers in Skh1 mice. Data also suggest that the enhancement of UVR
      induced skin cancers by chromate may not be oxidatively mediated since the
      antioxidant vitamin E as well as selenomethionine, found to prevent arsenite
      enhanced skin carcinogenesis, failed to suppress enhancement by chromate.

PMID- 17499831
TI  - Ability of a small, basic protein isolated from Russell's viper venom (Daboia
      russelli russelli) to induce renal tubular necrosis in mice.
AB  - Russell's viper venom (RVV) induced acute renal failure involves both direct and
      indirect nephrotoxic actions where the specific component/s are yet to be
      identified. A basic cytotoxin of 7.2kDa (RVV-7) has been identified as potential
      nephrotoxin. Autoradiographic experiments demonstrated that only RVV-7 among RVV
      toxins binds specifically to mice kidney membrane. Homogeneous preparation of RVV
      7 confirmed its necrotic cell killing property having EC(50) of 4.79+/
      3.28microM. Tissue distribution kinetics of RVV-7 in mice showed its higher
      localization in kidney compared to blood and liver. Role of inherent factor
      responsible for its localization in kidney was assessed after chemical
      inactivation of its cytotoxic activity. Cytotoxicity was neutralized by histidine
      modification but consequent alteration of in vivo distribution was insignificant.
      Classical concept of glomerular capillary wall (GCW) permselectivity barrier
      denotes that apart from size selectivity, GCW also restricts anionic proteins
      from filtration. Reducing the pI of RVV-7 by chemical manipulation of its surface
      positive charges resulted to decreased accumulation in kidney. Histological
      observations of kidney from mice treated in vivo with RVV-7 showed degenerated
      tubular epithelium. These findings indicate that basic character and small size
      of RVV-7 are favorable for its rapid accumulation in kidney leading to necrotic
      destruction of tubular epithelium.

PMID- 17499832
TI  - Rhesus monkeys mislocalize saccade targets flashed for 100ms around the time of a
      saccade.
AB  - Humans and monkeys mislocalize targets flashed around the time of a saccade.
      Here, we present data from three monkeys on a double-step task with a 100ms
      target duration. All three subjects mislocalized targets that were flashed around
      the time of the first saccade, in spite of long intersaccadic intervals. The
      error was consistently in the direction opposite that of the saccade, and
      occurred in some cases when the target presentation was entirely presaccadic.
      This is inconsistent with a theory invoking a damped representation of eye
      position, but it is consistent with the hypothesis that it is due to an error in
      peri-saccadic remapping.

PMID- 17499833
TI  - The relationship between spatial pooling and attention in saccadic and perceptual
      tasks.
AB  - Saccades aimed at spatially extended targets land reliably at central locations
      determined by pooling information across the target shape [Melcher, D., & Kowler,
      E. (1999). Shape, surfaces and saccades. Vision Research, 39, 2929-2946;
      Vishwanath, D., & Kowler, E. (2003). Localization of shapes: Eye movements and
      perception compared. Vision Research, 43, 1637-1653]. Previous findings of
      saccadic errors when attempting to look at a target in the midst of distractors
      encouraged suggestions that pooling occurs indiscriminately, with little or no
      influence of a selective filter to eliminate the influence of nearby distractors.
      To determine the effectiveness of filtering, saccadic localization was studied
      for saccades made to a set of target elements (discs) interleaved with an
      equivalent set of distractors of a different color. With such interleaved
      elements, selection and spatial pooling are constrained to occur over the same
      spatial region. The results showed that filtering was effective and saccadic
      landing position was determined mainly by the target elements. Concurrent
      perceptual judgments made about the same stimuli (estimating the mean size of
      either target or distractor discs) showed better performance for the target discs
      than distractors, confirming that perceptual attention was allocated to the set
      of target elements. These results: (1) support the role of attention in setting
      the input to the spatial pooling process that guides saccades to spatially
      extended targets, and (2) show that perceptual judgments of mean value, often
      thought to impose modest attentional demands, are not immune to the constraints
      of this pre-saccadic filter.

PMID- 17499834
TI  - Two distinct cone-opponent processes in the L+M luminance pathway.
AB  - We measured phase shifts between Long-wavelength cone (L-cone) and Middle
      wavelength cone (M-cone) signals as well as sensitivity in the luminance pathway
      either following a cone-silent substitution of colored background or on a steady
      colored background. In background substitution, the phase shifts between L- and M
      cone signals varied only slightly depending on the substituted color, whereas
      marked elevation of the threshold following the substitution of colored
      background was found. In contrast, the phase shifts, as well as threshold, varied
      largely, depending on the background color in the steady background. These facts
      suggest that suppression by the cone-opponent process for background color
      substitution is different from the one for a steady colored background.

PMID- 17499835
TI  - Mutual information of image fragments predicts categorization in humans:
      electrophysiological and behavioral evidence.
AB  - Computational models suggest that features of intermediate complexity (IC) play a
      central role in object categorization [Ullman, S., Vidal-Naquet, M., & Sali, E.
      (2002). Visual features of intermediate complexity and their use in
      classification. Nature Neuroscience, 5, 682-687.]. The critical aspect of these
      features is the amount of mutual information (MI) they deliver. We examined the
      relation between MI, human categorization and an electrophysiological response to
      IC features. Categorization performance correlated with MI level as well as with
      the amplitude of a posterior temporal potential, peaking around 270 ms. Hence, an
      objective MI measure predicts human object categorization performance and its
      underlying neural activity. These results demonstrate that informative IC
      features serve as categorization features in human vision.

PMID- 17499836
TI  - Superparamagnetic nanoparticles in tap water.
AB  - Magnetization measurements are a useful tool in the characterization of corrosion
      products formed in municipal water pipes made of iron or steel. Fine particles
      formed in corrosion processes exhibit superparamagnetic behavior. The size of
      such particles, which determines their capacity to adsorb hazardous species, can
      therefore be found from magnetic measurements. Application of this methodology to
      samples extracted from flowing and stagnant tap water, respectively, has shown
      that the flowing water samples contained multidomain (>100 nm) ferromagnetic
      particles as well as aggregates of very fine superparamagnetic subdomain
      particles. The sizes of the fine particles are of the order of 3.2-5.6 nm. In
      addition to small subdomain superparamagnetic particles stagnant water samples
      also contained larger subdomain particles with average dimensions of 59-67 nm.
      Both large and small subdomain particles were trapped by the fine charcoal in
      household filters.

PMID- 17499837
TI  - On-line sorption-based systems for determination of cadmium with atomic
      spectrometry detectors.
AB  - Determination of cadmium is often required in various environmental, biological
      and food samples as it is recognized worldwide as a toxic metal. However, these
      analysis with atomic spectrometry detectors are often difficult due to relatively
      low content of cadmium and complex matrices. Several preconcentration/separation
      procedures to determine cadmium have been devised, among them the methods based
      on sorbent extraction are the most popular. They can be easily implemented and
      controlled in flow injection (FI) or sequential injection (SI) systems to perform
      appropriate sample pretreatment. This work reviews the papers, published from
      1990, concerning procedures based on sorption principles for on-line
      determination of cadmium. They were compared using experimental enhancement
      factor (EF) and concentration efficiency (CE) values.

PMID- 17499838
TI  - Biological short-chain fatty acids (SCFAs) production from waste-activated sludge
      affected by surfactant.
AB  - Short-chain fatty acids (SCFAs), the preferred carbon sources for biological
      nutrient removal, are the important intermediate products in sludge anaerobic
      fermentation. Sodium dodecylbenzene sulfonate (SDBS) is a widespread used
      surfactant, which can be easily found in waste-activated sludge (WAS). In this
      investigation, the effect of SDBS on SCFAs production from WAS was investigated,
      and the potential of using fermentative SCFAs to promote enhanced biological
      phosphorus removal (EBPR) was tested. Results showed that the total SCFAs
      production increased significantly in the presence of SDBS at room temperature.
      At fermentation time of 6 days, the maximum SCFAs was 2599.1mg chemical oxygen
      demand (COD)/L in the presence of SDBS 0.02g/g, whereas it was only 339.1mg
      (COD)/L in the absence of SDBS. The SCFAs produced in the case of SDBS 0.02g/g
      and fermentation time 6 days consisted of acetic acid (27.1%), propionic acid
      (22.8%), iso-valeric acid (20.1%), iso-butyric acid (11.9%), n-butyric acid
      (10.4%) and n-valeric acid (7.7%). It was found that during sludge anaerobic
      fermentation, the solubilization of sludge particulate organic-carbon and
      hydrolysis of solubilized substrate as well as acidification of hydrolyzed
      products were all increased in the presence of SDBS, while the methane formation
      was decreased, the SCFAs production was therefore remarkably improved. Further
      investigation showed that the production of SCFAs enhanced by SDBS was caused
      mainly by biological effects, rather than by chemical effects and SDBS
      decomposition. With the fermentative SCFAs as the main carbon source, the EBPR
      maintained high phosphorus removal efficiency ( approximately 97%).

PMID- 17499839
TI  - Biodegradation of pyridine using aerobic granules in the presence of phenol.
AB  - Aerobic granules cultivated with 500 mg/L phenol medium effectively degraded
      pyridine at a concentration of 250-2500 mg/L; maximum degradation rate was 73.0
      mg pyridineg/VSS/h at 250 mg/L pyridine concentration. Phenol concentrations of
      500-2000 mg/L limited pyridine degradation in a competitive inhibition pattern,
      as interpreted using Michaelis-Menten kinetics with corresponding parameters
      V(max), K(m) and K(I) of 63.7 mg/Lh(-1), 827.8 and 1388.9 mg/L, respectively.
      Fluorescent staining and confocal laser scanning microscopy (CLSM) tests
      suggested that an active biomass accumulated at the granule outer layer.
      Denaturing gradient gel electrophoresis (DGGE) fingerprint profile demonstrated
      that dominating microbial strains exist in phenol and pyridine-degrading aerobic
      granules.

PMID- 17499840
TI  - Vegetation and plant food reconstruction of lowermost Bed II, Olduvai Gorge,
      using modern analogs.
AB  - Vegetation and plant foods for hominins of lowermost Bed II, Olduvai Gorge were
      modeled by examining vegetation in modern habitats in northern Tanzania (Lake
      Manyara, Ngorongoro, Serengeti) that are analogous to the paleolandscape in terms
      of climate, land forms, and soil types, as indicated by previous
      paleoenvironmental studies of Olduvai. Plant species in the modern habitats were
      identified in a series of sample plots, and those known to be eaten by modern
      humans, chimpanzees, or baboons were considered potentially edible for early
      hominins. Within the 50-80 kyr deposition of lowermost Bed II, periods of drier
      climate were characterized by low lake stands and a broad eastern lacustrine
      plain containing a mosaic of springs, marsh, woodland, and edaphic grassland.
      Based on results of this study, plant food diversity in each of those habitats
      was relatively low, but the mosaic nature of the area meant that hominins could
      reach several different habitat types within short distances, with access to
      potential plant foods including marsh plants, grass grains, roots, shrub fruits,
      edible parts from palms, leafy herbaceous plants, and Acacia pods, flowers, and
      gum. Based on Manyara analogs, a greater variety of plant foods, such as tree
      fruits (e.g., Ficus, Trichilia) and the roots and fruits of shrubs (e.g., Cordia,
      Salvadora) would be expected further east along the rivers in the lacustrine
      terrace and alluvial fans. Interfluves of the alluvial fans were probably less
      wooded and offered relatively fewer varieties of plant foods, but there is sparse
      paleoenvironmental evidence for the character of Olduvai's alluvial fans, making
      the choice of appropriate modern analogs difficult. In the western side of the
      basin, based on modern analogs in the Serengeti, riverine habitats provided the
      greatest variety of edible plant food species (e.g., Acacia, Grewia, Justicia).
      If the interfluves were grassland, then a large variety of potentially edible
      grasses and forbs were present seasonally. Periods of wetter climate resulted in
      a much expanded paleolake and a shrinking of the eastern lacustrine plain mosaic
      into a narrow zone. The dominant landscape features were then forest-lined rivers
      in the eastern alluvial fans, and rivers in the western side of the paleo-Olduvai
      basin were also better watered at these times, supporting denser woody vegetation
      with large varieties of edible fruits, leaves, and underground parts.

PMID- 17499841
TI  - Dynamics of arsenic in the mining sites of Pine Creek Geosyncline, Northern
      Australia.
AB  - The transportation and fixation of arsenic (As) in soil and sediments from five
      mine sites within the Pine Creek Geosyncline, Northern Territory, were examined
      based on measurements of operationally-defined fractions of As in soils, sediment
      and evaporates. Arsenic was mainly retained in sediments in the form iron
      arsenate (Fe-As). In wetland systems, As was retained as Fe-As together with
      calcium arsenate (Ca-As) from alkaline groundwater and organic-bound As from
      detrital material. In retention ponds As was retained as Fe-As, Ca-As and
      residual As (Res-As) up to 1700 mg/kg. Sediment traps can retain As from alkaline
      and acidic source seepages. The retention of Res-As and other mineral
      particulates during erosional or controlled process water discharges was
      associated with high Fe-As and organic-bound As in sediment. Arsenic was retained
      as Fe-As, Ca-As and residual As in 100 year old tailings at Millar's Battery,
      Union Reefs mine nearby McKinlay River and the small copper mine lease MLN 95
      adjacent Copperfield Creek nearby Pine Creek. Natural geo-mobilisation of As was
      observed in upstream sediments at Copperfield Creek (5-8 mg/kg), Mt. Bundey Creek
      (10-12 mg/kg), upstream Ryan's Creek (10-12 mg/kg) and downstream East branch
      Ryan's Creek (7 mg/kg). Erosion of As-containing mineralisation was observed in
      the McKinlay River upstream and downstream (23-26 mg/kg) and upstream Ryan's
      Creek boundary of the Goodall mine lease MLN 1049 (24-40 mg/kg). Overall, As was
      mainly retained in sediments in the form Fe-As. The concentration data for As
      were used to propose mechanisms of As dispersion and retention occurring at the
      various mine sites that can be utilised for future mine water management design
      to minimise As dispersion.

PMID- 17499842
TI  - The ebullition of hydrogen, carbon monoxide, methane, carbon dioxide and total
      gaseous mercury from the Cornwall Area of Concern.
AB  - This paper reports the first ebullitive fluxes of hydrogen (H2), carbon monoxide
      (CO), methane (CH4), carbon dioxide (CO2) and total gaseous mercury (TGM) from
      the Cornwall Area of Concern (CAC). Although sediments were contaminated with
      mercury, bubbling was a negligible source of mercury for the global atmosphere.
      Indeed, the average emission of TGM through ebullition was 0.04 pg m(-2) h(-1).
      Measurements of H2, CO, CH4 and CO2 trapped gas concentrations and fluxes were
      used as indicators of diagenesis processes. The CAC represented a significant
      regional source of CH4 since the estimated ebullitive fluxes (3.5 mg m(-2) h(-1))
      were similar to the CH4 emissions measured above typical flooded freshwater
      wetlands. As molecular diffusion is known as the main pathway of CO2 transport
      from water to the atmosphere, CO2 ebullitive fluxes were weak (0.39 mg m(-2) h(
      1)). Bubbling of CO (1.6 microg m(-2) h(-1)) was 10 folds less important than CO
      fluxes measured over flooded freshwater wetlands. Finally, H2 emissions (0.001
      microg m(-2) h(-1)) were negligible since the level of this trace gas is tightly
      regulated by microorganisms in anaerobic environments.

PMID- 17499843
TI  - Concentrations and patterns of organochlorine pesticides and PCBs in
      Mediterranean monk seals (Monachus monachus) from Western Sahara and Greece.
AB  - Blubber from Mediterranean monk seals (Monachus monachus) from the Western Sahara
      coast (Atlantic), sampled during 1996-1999, and from the Greek coast
      (Mediterranean), sampled during 1995-1999, was analyzed for organochlorine
      pollutants (OCs). In both populations, no significant difference was found
      between sexes. In the Atlantic population, mature females presented greater
      percentages of higher chlorinated PCB (polychlorinated biphenyl) congeners in
      relation to total PCBs (sum of 25 congeners) than pups, indicating a differential
      transfer of PCB congeners through lactation. In the Mediterranean, the reduced
      sample size of adult individuals precluded proper statistical investigation of
      age-related variation. Significant differences in concentrations and pollutant
      patterns were found between populations. Thus, Mediterranean individuals
      presented significantly higher levels of HCB (hexachlorobenzene), tPCB, and DDTs
      (dichlorodiphenyltrichloroethane) concentrations and DDE/tDDT and tDDT/tPCB
      ratios than their counterparts from the Atlantic. Moreover, the relative
      proportion of different congeners in relation to the total PCB load
      (congener/tPCB) was also different between the two areas. The 100*tDDT/tPCB ratio
      in Atlantic seals was 38.46, which indicates a predominance of industrial inputs
      over those associated with agriculture. Conversely, in the Mediterranean seal
      population, the 100*tDDT/tPCB ratio was 177.1, denoting a proportionally higher
      contribution of pollutants of agricultural origin.

PMID- 17499844
TI  - Prognostic significance of delays in diagnosis of pulmonary embolism.
AB  - STUDY OBJECTIVE: To investigate the prognostic significance of a diagnostic delay
      of greater than 1 week after symptom onset in patients with pulmonary embolism
      (PE). DESIGN: Prospective cohort study. LOCATION: Emergency Department of Ramon y
      Cajal Hospital, a 1500-bed tertiary-care center in Madrid, Spain. PATIENTS:
      Diagnosed with PE by objective testing between January 1, 2003, and June 30,
      2005. INTERVENTIONS: All patients received standard anticoagulation therapy
      during follow-up. ENDPOINTS: Death from any cause or symptomatic recurrent venous
      thromboembolism (VTE), confirmed by standard objective testing, within 3 months
      after PE diagnosis. RESULTS: Of the 397 patients with acute PE, 72 (18%) had a
      diagnostic delay while 325 (82%) did not. The all-cause mortality rate was 13.1%
      at 3 months (95% CI=9.8-16.4%); due to 9 (12.5%) deaths in the diagnostic delay
      group and 43 (13.2%) deaths in the group without diagnostic delay (OR 0.9; 95%
      CI=0.4-2.0). Though multivariate analysis of clinical variables at the time of PE
      diagnosis identified active cancer, heart failure and immobility for more than 4
      days as independent risk factors for death, diagnostic delay was not predictive.
      Recurrent VTE was observed in 3 (4.2%) of 72 patients with diagnostic delay and
      in 15 (4.6%) of 325 patients without diagnostic delay (odds ratio: 0.9; 95%
      CI=0.2-3.2). None of the variables analysed, including diagnostic delay, was
      associated with an increased risk of recurrent VTE during follow-up. CONCLUSIONS:
      Among survivors diagnosed with acute PE in the Emergency Department, we did not
      detect an association between a delay in diagnosis and an increased risk of death
      or VTE recurrence during the ensuing 3 months of treatment.

PMID- 17499845
TI  - Acute postoperative thrombotic thrombocytopenic purpura following hysterectomy
      and lymphadenectomy for endometrial cancer.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) in the acute postoperative
      setting is a recently recognized syndrome that, similar to classic or idiopathic
      TTP, presents variably with microangiopathic hemolytic anemia, thrombocytopenia,
      fever, renal failure, and mental status changes. Though most reports of
      postoperative TTP are in conjunction with cardiac or vascular surgery, it has
      also been reported following orthopedic and abdominal surgeries. CASE: We present
      a case of a 53 year-old female diagnosed with metastatic poorly differentiated
      endometrial cancer who developed TTP the day following her cytoreductive cancer
      surgery. CONCLUSION: To our knowledge, this represents the first reported case of
      postoperative TTP following gynecologic cancer surgery. Because the presentation
      can be confused with other early postoperative complications, awareness of this
      syndrome is essential as initiation of plasmapheresis can be life-saving.

PMID- 17499846
TI  - The effectiveness of nationally implemented smoking interventions in Denmark.
AB  - OBJECTIVE: The present study aimed to investigate the effectiveness of smoking
      cessation interventions at a national level. METHOD: A systematic follow-up was
      made of 3628 adults who participated in smoking cessation groups or in individual
      interventions in different settings in Denmark from January 2001 to March 2002.
      RESULTS: The rates of continued abstinence from smoking were estimated as 18% and
      16% after 6 and 12 months, respectively, for the 3628 participants from 101
      smoking cessation units. Among participants, who accomplished at least 75% of the
      intervention, the rates of non-smokers after six and twelve months were 23% and
      19%, respectively. Five of the investigated factors influenced continued
      abstinence after 12 months: gender, age, degree of nicotine dependence, the
      format and the setting of the cessation service. CONCLUSIONS: The study shows
      that it is possible to implement uniform smoking cessation interventions at a
      national level keeping the same abstinence rates as previously achieved in
      randomized clinical trials. The successful cessation interventions were run by
      nurses and equivalent staff that had received only 3 days of training and had no
      other particular therapeutic skills.

PMID- 17499848
TI  - ThermoTRP channels as modular proteins with allosteric gating.
AB  - Ion channels activate by sensing stimuli such as membrane voltage, ligand binding
      or temperature and transduce this information into conformational changes that
      open the channel pore. Thus, a key question in understanding ion channel function
      is how do the protein domains involved in sensing stimuli (sensors) and opening
      the pore (gates) communicate. In this regard, transient receptor potential (TRP)
      channels that confer thermosensation [A. Dhaka, V. Viswanath, A. Patapoutian, TRP
      ion channels and temperature sensation, Annu. Rev. Neurosci. 29 (2006) 135-161;
      I.S. Ramsey, M. Delling, D.E. Clapham, An introduction to TRP channels, Annu.
      Rev. Physiol. 68 (2006) 619-647] (thermoTRP; Q(10)>10) are unique to the extent
      that they integrate a variety of physical and chemical stimuli. In some cases
      such as, for example, the vanilloid receptor TRPV1 [M.J. Caterina, M.A.
      Schumacher, M. Tominaga, T.A. Rosen, J.D. Levine, D. Julius, The capsaicin
      receptor: a heat-activated ion channel in the pain pathway, Nature 389 (1997) 816
      824] and TRPA1 [G.M. Story, A.M. Peier, A.J. Reeve, S.R. Eid, J. Mosbacher, T.R.
      Hricik, T.J. Earley, A.C. Hergarden, D.A. Andersson, S.W. Hwang, P. McIntyre, T.
      Jegla, S. Bevan, A. Patapoutian, ANKTM1, a TRP-like channel expressed in
      nociceptive neurons, is activated by cold temperatures, Cell 112 (2003) 819-829;
      S. Jordt, D. Julius, Molecular basis for species-specific sensitivity to "hot"
      chilli peppers, Cell 108 (2002) 421-430] the integration of these stimuli elicit
      pain [M. Tominaga, M.J. Caterina, A.B. Malmberg, T.A. Rosen, H. Gilbert, K.
      Skinner, B.E. Raumann, A.I. Basbaum, D. Julius, The cloned capsaicin receptor
      integrates multiple pain-producing stimuli, Neuron 21 (1998) 531-543; M. Bandell,
      A. Dubin, M. Petrus, A. Orth, J. Mathur, S. Hwang, A. Patapoutian, High
      throughput random mutagenesis screen reveals TRPM8 residues specifically required
      for activation by menthol, Nat. Neurosci. 9 (2006) 466-468; S. Zurborg, B.
      Yurgionas, JA. Jira, O. Caspani, P.A. Heppenstall, Direct activation of the ion
      channel TRPA1 by Ca(2+), Nat. Neurosci. 10 (2007) 277-279]. These stimuli include
      voltage, pH, agonist binding, and temperature. Understanding how each of these
      distinct physiological signals regulate channel opening will be informative about
      the mechanical linkages that can act either independently or in concert to
      influence channel activation. In this paper we show that thermoTRP channel
      forming proteins are modular in the sense that certain structure or structures
      (modules) confer temperature-dependent regulation, whereas others confer voltage
      dependent regulation. We also discuss the thermodynamic basis of heat and cold
      activation in an effort to elucidate what confer to these channels the capability
      to be gated by temperature directly.

PMID- 17499849
TI  - The complex regulatory function of the ligand-binding domain of the inositol
      1,4,5-trisphosphate receptor.
AB  - The inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) can be divided in
      three functionally distinct regions: a ligand-binding domain, a modulatory domain
      and a channel domain. Numerous regulatory mechanisms including inter- and intra
      molecular protein-protein interactions and phosphorylation events act via these
      domains to regulate the function of the IP(3)R. Regulation at the level of the
      ligand-binding domain primarily affects the affinity for IP(3). The extent of
      IP(3)-induced Ca(2+) release (IICR) is, however, not only determined by the
      affinity for IP(3) but also by the effectiveness of the coupling between ligand
      binding and channel opening. As a result, regulation as well as malfunction of
      IICR may be affected by both steps in the activation mechanism. The 3D structures
      of the two subdomains of the ligand-binding domain have recently been determined
      by X-ray diffraction analysis. This allows a more detailed molecular explanation
      of the regulatory events situated at the ligand-binding domain of the IP(3)R. In
      this review, we will focus on recent structural and functional data on the ligand
      binding domain that have extended and clarified the view on the molecular
      mechanisms of IP(3)R regulation.

PMID- 17499850
TI  - cDNA cloning, expression and bioactivity of porcine BAFF.
AB  - B cell activating factor belonging to the tumor necrosis factor (TNF) family
      (BAFF) is critical for B cell survival, maturation and T cell activation by
      acting through its three receptors, BAFF-R, BCMA and TACI. In the present study,
      a porcine BAFF cDNA, designated pBAFF, was cloned by RT-PCR and rapid
      amplification of cDNA ends (RACE) strategies. The full-length cDNA of pBAFF
      consists of 805bp with a 702bp open reading frame, encoding 233 amino acids. The
      deduced amino acid sequence contains a predicted transmembrane domain and a
      putative furin protease cleavage site corresponding to other identified BAFF
      homologues. The amino acid similarity between the functional soluble parts of
      pBAFF and human BAFF (hBAFF) or chicken BAFF (cBAFF) is 93% and 85%,
      respectively, with identity at the amino acid level was 88% and 76%,
      respectively. The characteristic of the three-cysteine residues of BAFF is
      conserved in pBAFF. RT-PCR showed that BAFF is expressed in many tissues in the
      pig, including spleen, liver, lung, heart, intestine, kidney, thymus and PBLs.
      Recombinant soluble pBAFF (psBAFF) fused with His(6) tag was efficiently
      expressed in Escherichia coli BL21 (DE3) and its expression was confirmed by
      sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS-PAGE) and Western
      blotting. In vitro, purified psBAFF co-stimulates the proliferation of not only
      porcine B cells but also human B cells. In addition, hsBAFF binds to porcine B
      cells and has a positive effect on their proliferation. These findings indicate
      pBAFF plays an important role in proliferation of porcine B cells and functional
      cross-reactivity occurs between porcine and human BAFF. In vitro expression of
      bioactive psBAFF provides the basis for further investigation of its potential to
      be used as an immunoadjuvant for enhancing vaccine efficacy and an
      immunotherapeutic in pig. It also provides the basis for investigations on the
      role of BAFF in this important domestic species and an animal model for human
      diseases.

PMID- 17499851
TI  - Molecular characterization of field isolates and vaccine strains of infectious
      bursal disease virus.
AB  - The present investigation was conducted to study the genetic heterogenicity and
      molecular polymorphism among the field isolates and vaccine strains of infectious
      bursal disease virus (IBDV). Samples of bursa of Fabricius from 15 suspected
      outbreaks of infectious bursal disease (IBD) were subjected to agar gel
      precipitation test (AGPT), virus isolation and reverse transcription-polymerase
      chain reaction (RT-PCR) combined with restriction fragment length polymorphism
      (RFLP). Nine out of 15 samples were found positive in AGPT while 14 were found
      positive both by virus isolation and RT-PCR. PCR amplified 474bp fragment from
      the variable region of VP2. Sac I, Stu I, Alu I, Ssp I and Mbo I restriction
      enzymes were used for characterization of all the 14 IBDV isolates and four
      reference vaccine strains. Sac I, Stu I, Alu I and Ssp I could differentiate
      classical virulent IBD (cvIBD) vaccine virus strains from very virulent IBD
      (vvIBD) field isolates by their varying restriction patterns. Based on above
      results two field isolates (VPL and VMK) were placed in cvIBD virus group and 12
      field isolates were placed in vvIBD virus group. Virus neutralisation test (VNT)
      using rabbit raised Georgia strain anti-serum, however, could not differentiate
      between cvIBD virus and vvIBD virus. It was concluded that RT-PCR combined with
      RFLP assay using restriction enzymes Sac I, Stu I, Alu I and Ssp I can be used
      for rapid differentiation and classification of field isolates of IBDV.

PMID- 17499852
TI  - Cytotoxicity, genotoxicity and ecotoxicity assay using human cell and
      environmental species for the screening of the risk from pollutant exposure.
AB  - For the screening of the risk from environmental contamination, the
      cytotoxic/genotoxic effects of various model pollutants were determined using an
      in vivo system comprised of human HeLa cells; the ecotoxicity was also determined
      using the acute and genotoxicity tests on two aquatic sentinel species widely
      used in biomonitoring, namely, freshwater crustacean, Daphnia magna and larva of
      aquatic midge, Chironomus tentans. Nonylphenol (NP), bisphenol A (BPA), bis(2
      ethylhexyl) phthalate (DEPH) and paraquat dichloride (PQ) were used as the model
      pollutants. The results showed that exposure of HeLa cells to NP, BPA and DEHP
      was sufficient for the expression of noticeable genotoxic and cytotoxic effects.
      Ecotoxicity results showed that, as expected, D. magna was more sensitive than C.
      tentans to chemical exposure. BPA may exert a genotoxic effect on D. magna and C.
      tentans, given that DNA strand breaks increased in both species exposed to this
      compound, whereas NP-induced DNA damage occurred only in C. tentans. In vivo
      genotoxic data obtained in aquatic sentinel species could provide valuable
      information for freshwater quality monitoring. From the results of the present
      study, the use of cytotoxic, genotoxic and ecotoxic tests using human cell
      system, as well as, biomonitoring species, seems to be relevant for preliminary
      evaluation of the human health and ecological effects of pollutants and thus, a
      promising screening tool for environmental monitoring and risk assessment.

PMID- 17499853
TI  - The dichotomy of relative humidity on indoor air quality.
AB  - Dry and irritated mucous membranes of the eyes and airways are common symptoms
      reported in office-like environments. Earlier studies suggested that indoor
      pollutants were responsible. We have re-evaluated, by review of the literature,
      how low relative humidity (RH) may influence the immediately perceived indoor air
      quality (IAQ), including odour, and cause irritation symptoms (i.e. longer-term
      perceived IAQ). "Relative humidity" were searched in major databases, and
      combined with: air quality, cabin air, dry eyes, formaldehyde, inflammation,
      mucous membranes, offices, ozone, pungency, sensory irritation, particles,
      precorneal tear film, sick building syndrome, stuffy air, and VOCs. The impact of
      RH on the immediately and longer-term perceived IAQ by VOCs, ozone, and particles
      is complex, because both the thermodynamic condition and the emission
      characteristics of building materials are influenced. Epidemiological, clinical,
      and human exposure studies indicate that low RH plays a role in the increase of
      reporting eye irritation symptoms and alteration of the precorneal tear film.
      These effects may be exacerbated during visual display unit work. The
      recommendation that IAQ should be "dry and cool" may be useful for evaluation of
      the immediately perceived IAQ in material emission testing, but should be
      considered cautiously about the development of irritation symptoms in eyes and
      upper airways during a workday. Studies indicate that RH about 40% is better for
      the eyes and upper airways than levels below 30%. The optimal RH may differ for
      the eyes and the airways regarding desiccation of the mucous membranes.

PMID- 17499854
TI  - A chronically implantable, hybrid cannula-electrode device for assessing the
      effects of molecules on electrophysiological signals in freely behaving animals.
AB  - We describe a device for assessing the effects of diffusible molecules on
      electrophysiological recordings from multiple neurons. This device allows for the
      infusion of reagents through a cannula located among an array of micro
      electrodes. The device can easily be customized to target specific neural
      structures. It is designed to be chronically implanted so that isolated neural
      units and local field potentials are recorded over the course of several weeks or
      months. Multivariate statistical and spectral analysis of electrophysiological
      signals acquired using this system could quantitatively identify electrical
      "signatures" of therapeutically useful drugs.

PMID- 17499855
TI  - In search of Aristotle: temperament, human nature, melancholia, creativity and
      eminence.
AB  - Is suffering associated with melancholia and "madness" necessary for artistic
      creativity and eminence? Or do creativity and leadership have something to do
      with the temperaments associated with affective disease? We integrate concepts
      dating back to Greek psychological medicine and philosophy--especially work
      attributed to Aristotle--with modern data-based examination of the role of
      cyclothymic and related temperaments in the interface between mixity, the bipolar
      spectrum and normality. We place our query within the general framework of
      evolutionary biology and human nature. In doing so, we propose that affective
      disease--including mania and associated psychotic states--exist because they
      serve as the genetic reservoir for adaptive temperaments and the genes for
      genius. Affective disorder can therefore be regarded as the price of exceptional
      greatness. Thus, creative and eminent individuals, by virtue of their being
      exceptional, occupy a somewhat unstable terrain between temperament and affective
      disease.

PMID- 17499856
TI  - CSF 5-HIAA and DST non-suppression -independent biomarkers in suicide attempters?
AB  - BACKGROUND: Two major biomarkers of suicidal behaviour; low 5-hydroxyindoleacetic
      acid (5-HIAA) in the cerebrospinal fluid (CSF) and non-suppression in the
      dexamethasone suppression test (DST) have evidence for predictive power for
      suicide in mood disorders. Previous suicide attempt is the most robust clinical
      risk factor. PURPOSE OF STUDY: To study the interrelationship of suicide risk
      factors: low CSF 5-HIAA and the DST non-suppression in mood disorder patients
      with and without an index suicide attempt. METHODS: Fifty-eight hospitalised mood
      disorder patients (twenty-five with an index suicide attempt), who were not
      receiving any treatment with antidepressants, underwent lumbar puncture and DST.
      Plasma cortisol levels were determined from blood samples drawn the following day
      at 8:00 a.m., 4:00 p.m. and 11:00 p.m. and analysed in relation to CSF 5-HIAA.
      RESULTS: In the sample as a whole, the serum cortisol level at 4:00 p.m. showed a
      significant positive correlation to CSF 5-HIAA (r=0.3, p<0.02). In the patients
      with an index suicide attempt, the serum cortisol at 4.00 p.m. correlated
      positively with CSF 5-HIAA (r=0.65, p<0.0006), but not in the non-attempters
      (NS). CONCLUSION: The positive correlation means that low CSF 5-HIAA and DST non
      suppression are relatively independent biomarkers of suicide risk in suicide
      attempters. The interrelation of the two systems seems to be different in suicide
      attempters compared to depressed inpatients without suicide attempt.

PMID- 17499857
TI  - An anthropological perspective on the evolutionary context of preeclampsia in
      humans.
AB  - Preeclampsia/eclampsia is a dangerous condition unique to humans that is
      associated with an energetically expensive developing fetal brain and extremely
      invasive implantation of the trophoblast. We review here the evolutionary history
      of human pregnancy and childbirth to set a context for evolutionary hypotheses
      about the origin of preeclampsia. Humans are characterized by having large
      brains, bipedal locomotion and helpless newborns. These distinctive aspects of
      our biology arose independently but together constrain pregnancy and childbirth
      leading to an unusual mechanism of birth, cephalopelvic disproportion, shoulder
      dystocia, difficult labors, and neonates requiring high levels of parental care.
      Our cultural adaptation in the form of assistance during childbirth and intensive
      parental investment make it possible to balance those constraints. Preeclampsia
      probably arose only after the increase in human brain size and modern human
      mechanism of birth. Like the other risks of childbirth, preeclampsia also
      represents a risk associated with these distinctive aspects of human pregnancy
      and childbirth and is mitigated today by medical intervention. We speculate that,
      like assistance during childbirth, cultural intervention during pregnancy may
      extend into the past.

PMID- 17499858
TI  - Paralysis of CD4(+)CD25(+) regulatory T cell response in chronic autoimmune
      encephalomyelitis.
AB  - Increasing evidence strongly suggest that CD4(+)CD25(+) regulatory T (Treg) cells
      play a pivotal role in suppressing the development of autoimmune diseases.
      However, it remains poorly understood how these cells are involved in the
      persistence of, or recovery from, the diseases. In the present study, we examined
      the role of CD4(+)CD25(+) Treg cells in chronic EAE and compared the results with
      those obtained in acute EAE. In EAE lesions, CD25(+) cells decreased rapidly at
      the beginning of chronic EAE, whereas these cells were maintained at high levels
      during the recovery from acute EAE. The number of Foxp3(+)CD4(+)CD25(+) Treg and
      levels of Foxp3 mRNA in the lymphoid organ were significantly lower in chronic
      EAE. Importantly, the regulatory function of individual CD4(+)CD25(+) Treg cells
      was maintained in animals with chronic EAE. Furthermore, adoptive transfer of
      activated CD4(+)CD25(+) Treg cells suppressed the development of chronic EAE.
      These findings suggest that impairment of the CD4(+)CD25(+) Treg response is
      critical for development of chronic autoimmune diseases, and can be adjustable by
      autologous Treg transplantation.

PMID- 17499859
TI  - Healing time, long-term result and effects of stem cell treatment in acute
      tympanic membrane perforation.
AB  - OBJECTIVE: The incidence of otitis media in children between the age of 2 and 6
      years is well documented. Repeated attacks may cause acute and chronic
      perforations. The surgical treatment for repairing chronic perforation is quite
      uncomfortable for the patients of this age group because of the invasiveness of
      this treatment. The aim of this study was to determine the long-term influence of
      embryonic stem cells on acute perforations and the effect of gelatin as a vehicle
      for applied stem cells. The possibility of teratogenic effects of the stem cells
      was also observed. METHODS: Bilateral laser myringotomy was performed in 17 adult
      Sprague-Dawley rats, divided into two groups. Gelatin, a substance suitable as
      vehicle for bioactive material was used bilaterally around the perforation in
      group A, to serve as a scaffold for repairing tissue. The stem cells were used in
      the right tympanic membrane perforation leaving the left tympanic membrane as a
      control. The animals in group B received the same treatment except for the use of
      gelatin and in addition received an immuno-suppressive agent. After half a year
      of observation the mechanical stiffness of the tympanic membrane was measured by
      moire interferometry for group B and the morphological study was performed by
      light microscopy for both groups A and B and electron microscopy for group A.
      RESULTS: Stem cell treated ears did not show any enhanced healing of the
      perforation although a marked thickening of the lamina propria was observed
      compared with control group. After half a year the strength and the stiffness of
      the tympanic membrane was almost the same for both treated and untreated ears. No
      evidence of teratoma was found after half a year. CONCLUSION: This study suggests
      that the stem cells stimulate the proliferation of connective tissue and fibers
      in the lamina propria, possibly mediated by secreted substances, although the
      stiffness properties do not seem to be altered. The use of gelatin does not seem
      to enhance the healing process of the tympanic membrane perforation.

PMID- 17499860
TI  - Human gamma-frequency oscillations associated with attention and memory.
AB  - Both theoretical and experimental animal work supports the hypothesis that
      transient oscillatory synchronization of neuronal assemblies at gamma frequencies
      (30-100 Hz) is closely associated with sensory processing. Recent data from
      recordings in animals and humans have suggested that gamma-frequency activity
      also has an important role in attention and both working and long-term memory.
      The involvement of gamma-band synchronization in various cognitive paradigms in
      humans is currently being investigated using intracranial and high-density
      electro- and magnetoencephalography recordings. Here, we discuss recent findings
      demonstrating human gamma-frequency activity associated with attention and memory
      in both sensory and non-sensory areas. Because oscillatory gamma-frequency
      activity has an important role in neuronal communication and synaptic plasticity,
      it could provide a key for understanding neuronal processing in both local and
      distributed cortical networks engaged in complex cognitive functions. This review
      is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations:
      the beauty and the beast, based on presentations at the annual INMED/TINS
      symposium (http://inmednet.com).

PMID- 17499861
TI  - Proteome analysis of Leishmania (Viannia) braziliensis by two-dimensional gel
      electrophoresis and mass spectrometry.
AB  - Leishmania (Viannia) braziliensis, a protozoan parasite widespread in the New
      World, is responsible for the infection of different mammal orders, including
      humans. This species is considered to be a major etiological agent of American
      cutaneous leishmaniasis. A proteomic study was carried out to identify proteins
      expressed by L. (V.) braziliensis. One hundred and one spots representing 75
      protein entries were identified by MALDI-TOF-TOF. Isoelectric point values
      estimated by gel electrophoresis matched closely with predicted values, although
      some discrepancies existed suggesting that post-translational protein
      modifications may be common in L. braziliensis. Moreover, 20 hypothetical
      proteins were experimentally identified. Identified proteins were classified into
      15 groups according to biological process. Among the proteins identified,
      approximately 40% have not been previously reported in a proteomic map of
      Leishmania. In addition, a number of potential virulence factors and drug targets
      were identified in this protein map, including some proteins associated with the
      metastatic phenotype. This study describes the first compilation of a proteomic
      reference map for L. braziliensis (pI 4-7, M(r) 10-130 kDa) and provides a very
      useful tool for comparative studies of strains isolated from patients presenting
      different clinical manifestations of leishmaniasis as well as a potential tool to
      identify markers for clinical diagnosis, therapeutics, and prognosis.

PMID- 17499862
TI  - Identification and mapping of protein kinase A binding sites in the costameric
      protein myospryn.
AB  - Recently we identified a novel target gene of MEF2A named myospryn that encodes a
      large, muscle-specific, costamere-restricted alpha-actinin binding protein.
      Myospryn belongs to the tripartite motif (TRIM) superfamily of proteins and was
      independently identified as a dysbindin-interacting protein. Dysbindin is
      associated with alpha-dystrobrevin, a component of the dystrophin-glycoprotein
      complex (DGC) in muscle. Apart from these initial findings little else is known
      regarding the potential function of myospryn in striated muscle. Here we reveal
      that myospryn is an anchoring protein for protein kinase A (PKA) (or AKAP) whose
      closest homolog is AKAP12, also known as gravin/AKAP250/SSeCKS. We demonstrate
      that myospryn co-localizes with RII alpha, a type II regulatory subunit of PKA,
      at the peripheral Z-disc/costameric region in striated muscle. Myospryn interacts
      with RII alpha and this scaffolding function has been evolutionarily conserved as
      the zebrafish ortholog also interacts with PKA. Moreover, myospryn serves as a
      substrate for PKA. These findings point to localized PKA signaling at the muscle
      costamere.

PMID- 17499863
TI  - Comparison of the efficacy of metoprolol and carvedilol for preventing atrial
      fibrillation after coronary bypass surgery.
AB  - BACKGROUND: Atrial fibrillation (AF) occurs frequently after coronary artery
      bypass grafting (CABG) and often results in prolonged postsurgical hospital stays
      and increased mortality and morbidity. Beta blockers are known to prevent
      postoperative AF. In this prospective study, we investigated the efficacy of
      carvedilol compared with metoprolol succinate in preventing postoperative AF.
      METHODS: Subjects included 110 patients (31 women, 79 men; mean age, 60+/-10
      years, range, 39-82 years) who had undergone CABG. Patients were randomized to
      receive either metoprolol or carvedilol, and all patients received the drugs 3
      days prior to surgery. Metoprolol was started at 50 mg twice daily and carvedilol
      was started at 12.5 mg twice daily. The doses were titrated according to the
      patients' hemodynamic responses. All patients were monitored for 3 days after the
      surgery. RESULTS: Of the 110 patients, 55 (50%) were treated with metoprolol
      succinate, and 55 (50%) were treated with carvedilol. Baseline characteristics
      and operative data of the patients did not differ between groups. During follow
      up, 20 patients (36%) in the metoprolol group and 9 patients (16%) in the
      carvedilol group developed AF (P=0.029). Multiple stepwise logistic regression
      analysis showed that metoprolol use, older age, and impaired left ventricular
      ejection fraction were independent risk factors for developing AF, and carvedilol
      use was found to be independently related to sinus rhythm maintenance after CABG
      (P=0.02). CONCLUSIONS: These results show that carvedilol is superior to
      metoprolol in decreasing development of early postoperative AF.

PMID- 17499864
TI  - Potential demographic and baselines variables for risk stratification of high
      risk post-myocardial infarction patients in the era of implantable cardioverter
      defibrillator--a prognostic indicator.
AB  - BACKGROUND: Risk stratification after myocardial infarction (MI) remains
      expensive and disappointing. We designed a prognostic indicator using demographic
      information to select patients at risk of dying after MI. METHOD AND RESULTS: We
      combined individual patient data from the placebo arms of EMIAT, CAMIAT, TRACE
      and DIAMOND-MI with LVEF <or=40% or ventricular arrhythmias (i.e. >10 ventricular
      premature beats/hour or a run of ventricular tachycardia). Risk factors for
      mortality beginning at day 45 post-MI up to 2 years were examined using Cox
      regression analysis. Risk scores were derived from the equation of a Cox
      regression model containing only significant variables. The prognostic index was
      the sum of the individual contribution from the risk factors. 2707 patients were
      pooled (age: 66 (23-92) years, 78.8% M) with 480 deaths at 2-years (44%
      arrhythmic and 35.6% non-arrhythmic cardiac deaths). Variables predicting
      mortality were age, sex, previous MI or angina, hypertension, diabetes, systolic
      blood pressure, heart rate, NYHA functional class and non-Q wave infarct on
      electrocardiogram. Distinct survival curves were obtained for 3 risk groups based
      on the median and inter-quartile range for the prognostic index. In the high-risk
      group, up to 40% of patients died (all-cause mortality), 19.1% died of arrhythmic
      and 18.2% died of non-arrhythmic cardiac causes at 2-years. CONCLUSION: In post
      MI patients with LVEF <or=40% or frequent ventricular premature beats, the
      additional use of a simple prognostic indicator based on demographic information
      was able to provide clinically meaningful risk stratification on patients that
      were at high risk of dying and may be used to identify patients for prophylactic
      implantable cardioverter-defibrillator therapy.

PMID- 17499865
TI  - Comparison of four different methods for extraction of Stachybotrys chartarum
      spore DNA and verification by real-time PCR.
AB  - A comparison of four different methods for the extraction of spore DNA from
      Stachybotrys chartarum was conducted. Spore DNA was extracted and purified using
      either one of three different commercial kits or water. All preparations utilized
      bead milling. Genomic DNA extracted from 10(1) to 10(7) spores was assessed by
      both agarose gel electrophoresis and real-time quantitative polymerase chain
      reaction (qPCR) performed against multi-copy (rRNA) and single-(tubulin) gene
      targets. The spore isolation technique we employed was verified to be pure by
      light microscopy. Although all preparatory methods led to successful detection by
      qPCR, S. chartarum spore DNA prepared using the Qiagen Plant kit was notably
      better over the extraction range.

PMID- 17499866
TI  - Regulation of Cited2 expression provides a functional link between translational
      and transcriptional responses during hypoxia.
AB  - BACKGROUND AND PURPOSE: Protein synthesis rates are greatly reduced under hypoxic
      conditions as a consequence of an overall inhibition of mRNA translation. Certain
      specific mRNA species have the ability to escape this general translational
      repression. At the cellular level this results in differential protein expression
      during hypoxic conditions. The objective of this study was to characterize the
      translational regulation of the postulated HIF-1alpha antagonist Cited2.
      MATERIALS AND METHODS: DU145 prostate carcinoma cells and mouse embryonic
      fibroblasts with a homozygous knock-in mutation for eIF2alpha (S51A) or wild-type
      eIF2alpha were exposed to severe hypoxia after which both total mRNA and
      efficiently translated mRNA were isolated. Quantitative RT-PCR was used to
      measure and compare changes in transcription (total mRNA) with changes in
      translation (efficiently translated mRNA fraction). RESULTS: We show using HIF
      1alpha null MEF cells that transcriptional induction of Cited2 during hypoxia is
      dependent on HIF-1alpha. Although global mRNA translation is inhibited during
      hypoxia Cited2 mRNA remains efficiently translated. An evolutionary conserved
      upstream open reading frame (uORF) in the 5'UTR of Cited2 did not stimulate
      translation in an eIF2alpha dependent manner during hypoxia. CONCLUSIONS:
      Selective translation Cited2 by an eIF2alpha independent mechanism establishes a
      link between translation and HIF-1 dependent transcription during hypoxia.

PMID- 17499867
TI  - Genetic determination of chromosomal radiosensitivities in G0- and G2-phase human
      lymphocytes.
AB  - BACKGROUND AND PURPOSE: The radiosensitivity of human lymphocytes measured using
      a G0- or G2-assay has been linked with an individual's risk of developing normal
      tissue complications following radiotherapy. This study was performed to increase
      basic knowledge of the genetics of the human radiation response, and chromosomal
      aberration induction in particular. MATERIALS AND METHODS: The study was carried
      out with blood samples taken from 15 monozygotic twin pairs. G0-assay was
      performed for cells irradiated with 6 Gy counting only deletions and G2-assay for
      cells irradiated with 0.5 Gy scoring only chromatid breaks. RESULTS: The mean
      number of deletions measured at 6 Gy for all 30 samples using the G0-assay
      amounted to 2.96+/-0.37 (means+/-SD), which corresponds to a coefficient of
      variation (CV) of 13%. There is a highly significant intra-pair correlation for
      this number among twins (r(2)=0.911) demonstrating that this parameter is mostly
      determined by genetic factors. According to the mean number of deletions, a
      theoretical classification based on the definition < or = MV-SD as resistant,
      MV+/-SD as normal and > or = MV+SD as sensitive was made, identifying two pairs
      as sensitive or resistant, respectively, while nine were normal and two pairs are
      intermediate. For chromatid breaks measured at 0.5 Gy with the G2-assay the mean
      number was 1.35+/-0.42 (means+/-SD) corresponding to a CV of 31%. There was again
      a strong intra-pair correlation among twins with r(2)=0.837 showing that this
      sensitivity is also determined mostly by genetic factors. There was, however, no
      inter-assay correlation between the G0- and G2-sensitivity (r(2)=0.006)
      demonstrating that these two sensitivities depend on different genetic factors.
      CONCLUSION: The chromosomal radiosensitivity of lymphocytes as defined by G0- or
      G2-assay is largely determined by different genetic factors, which may allow the
      use of genetic profiling as an indicator of the respective individual
      radiosensitivity.

PMID- 17499869
TI  - Interrelation amongst differentiation, senescence and genetic instability in long
      term cultures of fibroblasts exposed to different radiation qualities.
AB  - BACKGROUND AND PURPOSE: The goal of the present study was to investigate aging
      and genetic instability in the progeny of human fibroblasts exposed to X-rays and
      carbon ions. MATERIALS AND METHODS: Following irradiation, cells were regularly
      subcultured until senescence. At selected time-points BrdU-labelling index,
      expression of cell cycle related proteins, cell differentiation pattern and
      chromosome aberrations were assessed. RESULTS: After exposure, an immediate cell
      cycle arrest occurred followed by a period of a few weeks where premature
      differentiation and senescence were observed. In all cultures cycling cells
      expressing low levels of cell cycle inhibiting proteins were present and finally
      dominated the populations. About 5months after exposure, the cellular and
      molecular changes attributed to differentiation and senescence reappeared and
      persisted. Concurrently, genetic instability was observed, but the aberration
      yields and types differed between repeated experiments. The descendants of cells
      exposed to carbon ions did not senesce earlier and displayed a similar rate of
      genetic instability as the X-ray progeny. For high doses an impaired cell cycle
      regulation and extended life span was observed, but finally cell proliferation
      ceased in all populations. CONCLUSIONS: The descendants of irradiated fibroblasts
      undergo stepwise senescence and differentiation. Genetic instability is frequent
      and an extension of the life span may occur.

PMID- 17499868
TI  - Differential risk assessments from five hypoxia specific assays: The basis for
      biologically adapted individualized radiotherapy in advanced head and neck cancer
      patients.
AB  - PURPOSE: Hypoxia adversely relates with prognosis in human tumours. Five hypoxia
      specific predictive marker assays were compared and correlated with definitive
      radiotherapy. PATIENTS AND METHODS: Sixty-seven patients with advanced head and
      neck carcinomas were studied for pre-treatment plasma osteopontin measured by
      ELISA, tumour oxygenation status using pO(2) needle electrodes and tumour
      osteopontin, hypoxia inducible factor 1alpha (HIF-1alpha) and carboxyanhydrase 9
      (CA9) by immunohistochemistry. The primary treatment was radiotherapy and the
      hypoxic radiosensitizer nimorazole. Loco-regional tumour control was evaluated at
      5 years. RESULTS: All five markers showed inter-tumour variability. Inter-marker
      correlations were inconsistent. Only plasma osteopontin inversely correlated with
      median tumour pO(2), (p=0.02, r=0.28) and CA9 correlated with HIF-1alpha (p<0.01,
      r=0.45). In Kaplan-Meier analysis high plasma osteopontin, high HIF-1alpha and
      high proportion of tumour pO(2)2.5mmHg (HP(2.5)) related significantly with
      poorer loco-regional control, whereas CA9 and tumour osteopontin failed to
      predict loco-regional control in this set dataset. When analyzing Hb, stage, and
      the five markers by competing risks HP(2.5) was the strongest variable to predict
      for loco-regional tumour control. CONCLUSION: There was diversity and lack of
      correlation among five different hypoxia assays within individual tumours. High
      plasma osteopontin, high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg
      (HP(2.5)) related significantly with poorer loco-regional control, whereas CA9
      and tumour OPN failed to predict local control.

PMID- 17499870
TI  - Assessment of secondary patient motion induced by automated couch movement during
      on-line 6 dimensional repositioning in prostate cancer treatment.
AB  - BACKGROUND AND PURPOSE: The purpose of this study is to assess retrospectively
      secondary patient motion induced by 6D patient setup correction. MATERIALS AND
      METHODS: For 104 patients, treated with Novalis, 6D setup correction prior to
      treatment was performed by ExacTrac5.0/NovalisBody in combination with the
      Robotic Tilt Module mounted underneath the Exact Couch top. This 6D correction
      might induce additional setup errors due to patient reaction against the
      rotations. To evaluate induced secondary motion, the 6D setup correction is
      verified and evaluated with respect to the tolerance limits. RESULTS: The
      majority of measured secondary motions are found within the tolerance limits.
      Detected secondary motions are mostly found in longitudinal shifts and lateral
      rotations, and mainly found in only 1 dimension during the same verification. The
      verifications indicate that the patient population can be divided into a group
      that hardly moves and a group that moves throughout all 6D setup corrections. The
      patient's behavior can be predicted by the evaluation of the first five fractions
      as none of the patients demonstrate a learning curve during the treatment.
      CONCLUSIONS: 6D setup correction does not induce secondary motion for the
      majority of the patients and can therefore be applied for all treatment
      indications.

PMID- 17499871
TI  - Bladder extension variability during pelvic external beam radiotherapy with a
      full or empty bladder.
AB  - BACKGROUND AND PURPOSE: Varying bladder fillings during radiotherapy lead to a
      changing dose-volume load to the bladder and adjacent structures. The aim of the
      study was to compare the extent of bladder wall movements during parallel series
      with full bladder (FB) and empty bladder (EB). MATERIALS AND METHODS: Three
      hundred and forty serial computed tomography (CT) scans were performed in 50
      patients scheduled for primary and postoperative radiotherapy for prostate
      cancer. Each patient underwent two CT scans (with FB and EB) before and 2-3 times
      during radiotherapy. Displacements of the bladder wall were compared and
      correlated with changing bladder fillings. RESULTS: The variability of FB was
      larger compared to EB volume (standard deviation of 124 cc and 56 cc; p<0.01),
      but significant bladder wall displacement variabilities were only found at the
      anterior and superior borders. Within a bladder volume range between -100 and
      +200 ml relative to the FB planning scan, the mean bladder wall displacement
      remained < 5 mm at the inferior, lateral, and posterior borders - as opposed to
      15 and 21 mm at the anterior and superior borders. CONCLUSIONS: Treating the
      pelvis with EB compared to FB, bladder wall displacement can be only reduced at
      the superior and anterior borders. FB wall displacements are comparable with EB
      displacements at all other borders.

PMID- 17499872
TI  - Regional variations of cytochrome oxidase activity in the central auditory system
      of Relnrl-Orl (reeler) mutant mice.
AB  - Despite preserved cell differentiation, the Reln(rl-Orl) phenotype comprises
      laminar abnormalities of cell position in auditory cortex and dorsal cochlear
      nucleus. The metabolic consequences of the cell ectopias were determined by
      estimating cytochrome oxidase (CO) activity, a marker of neuronal activity. CO
      activity increased in the granular cell layer of dorsal cochlear nucleus,
      trapezoid body nucleus, intermediate lateral lemniscus, central and external
      inferior colliculus, and pyramidal cell layer of primary auditory cortex. On the
      contrary, CO activity decreased in the superficial molecular layer of dorsal
      cochlear nucleus as well as in the medioventral periolivary nucleus. These
      metabolic variations are discussed in terms of their possible relation to
      morphologic anomalies observed in the mutant.

PMID- 17499874
TI  - Reconditioning in patients with rheumatoid arthritis.
AB  - Rheumatologists traditionally have recommended to rheumatoid arthritis (RA)
      patients that they avoid dynamic and weight-bearing exercises because of concerns
      about aggravating joint inflammation and accelerating joint damage in such
      patients. These restrictions may lead to inadequate levels of physical activity
      and deconditioning. OBJECTIVE: To review the literature on tolerance and benefits
      of conditioning training, including dynamic and weight-bearing activities in RA
      patients. MATERIALS AND METHODS: Medline and Cochrane databases were searched
      with the keywords RA, rehabilitation, physical therapy, exercise, reconditioning,
      and rest. RESULTS: Rest therapy is more deleterious than beneficial in most
      patients with RA and may lead to deconditioning. Dynamic and aerobic exercises do
      not aggravate joint inflammation and do not accelerate joint damage in such
      patients. The important goal of reconditioning patients with RA is the prevention
      of functional decline. Conditioning programs designed to prevent widespread
      morbidities in healthy subjects are attainable by most RA patients, but an
      individualized approach to exercise is required. CONCLUSION: RA patients need to
      be persuaded about the effectiveness and safety of moderate and even high
      intensity exercise.

PMID- 17499873
TI  - Time courses of brain activation and their implications for function: a
      multichannel near-infrared spectroscopy study during finger tapping.
AB  - The time courses of brain activation were monitored during a finger tapping task
      using multichannel near-infrared spectroscopy with a time resolution of 0.1s in
      30 healthy volunteers. Task-induced brain activations were demonstrated as
      significant increases in oxygenated hemoglobin concentration ([oxy-Hb]) in a
      broad area around the motor cortex and significant decreases in deoxygenated
      hemoglobin concentration ([deoxy-Hb]) in a more restricted area, with a large
      degree of activation in the contralateral hemisphere. The time courses of the
      [oxy-Hb] changes varied depending on channel location: sustained activation
      across the task period in the motor cortex, transient activation during the
      initial segments of the task period in the somatosensory cortex, and accumulating
      activation along the task period in the frontal lobe. These characteristics are
      assumed to reflect the functional roles of the brain structures during the task
      period, that is, the execution, sensory monitoring, and maintenance of finger
      tapping.

PMID- 17499876
TI  - Low rate of screening for gestational diabetes mellitus in region Centre, France.

PMID- 17499877
TI  - Early manifestation of cardiovascular disease risk factors in offspring of
      mothers with previous history of gestational diabetes mellitus.
AB  - This study investigated the long-term adverse effects of maternal gestational
      diabetes mellitus (GDM) on cardiovascular disease (CVD) risk factors in
      offspring. A total of 298 offspring (202 offspring of GDM mothers and 96
      offspring of mothers with impaired glucose tolerance [IGT]) participated in the
      study. CVD risk factors included elevated body mass index (BMI), skinfold
      thickness, body fat, blood pressure, lipid profiles, and glucose values measured
      with a 2h oral glucose tolerance test. The BMI of offspring >or=5 years of age of
      GDM mothers was significantly higher than that of offspring of mothers with IGT
      when analysed according to age. In offspring of GDM mothers, CVD risk factors
      were positively correlated with age, except for lipid profiles. A significant
      negative relationship between age and BMI was observed in offspring of IGT
      mothers. The slope of the linear regression lines for BMI and fasting plasma
      insulin levels with age were significantly steeper for the offspring of GDM
      mothers than for those of IGT mothers. We conclude that childhood obesity, as
      well as altered glucose metabolism influenced by the maternal uterine
      environment, is more likely with advancing years in the offspring of GDM mothers
      than in the offspring of IGT mothers.

PMID- 17499878
TI  - Hip2Norm: an object-oriented cross-platform program for 3D analysis of hip joint
      morphology using 2D pelvic radiographs.
AB  - We developed an object-oriented cross-platform program to perform three
      dimensional (3D) analysis of hip joint morphology using two-dimensional (2D)
      anteroposterior (AP) pelvic radiographs. Landmarks extracted from 2D AP pelvic
      radiographs and optionally an additional lateral pelvic X-ray were combined with
      a cone beam projection model to reconstruct 3D hip joints. Since individual
      pelvic orientation can vary considerably, a method for standardizing pelvic
      orientation was implemented to determine the absolute tilt/rotation. The
      evaluation of anatomically morphologic differences was achieved by reconstructing
      the projected acetabular rim and the measured hip parameters as if obtained in a
      standardized neutral orientation. The program had been successfully used to
      interactively objectify acetabular version in hips with femoro-acetabular
      impingement or developmental dysplasia. Hip(2)Norm is written in object-oriented
      programming language C++ using cross-platform software Qt (TrollTech, Oslo,
      Norway) for graphical user interface (GUI) and is transportable to any platform.

PMID- 17499879
TI  - U(VI) adsorption on aquifer sediments at the Hanford Site.
AB  - Aquifer sediments collected via split-spoon sampling in two new groundwater wells
      in the 200-UP-1 operable unit at the Hanford Site were characterized and showed
      typical Ringold Unit E Formation properties dominated by gravel and sand. High
      iron-oxide content in Fe oxide/clay coatings caused the highest U(VI) adsorption
      as quantified by batch K(d) values, indicating iron oxides are the key solid
      adsorbent in the 200-UP-1 sediments that affect U(VI) fate and mobility. Even
      though U(VI) adsorption on the gravel-sized fraction of the sediments is
      considered to be negligible, careful characterization should be conducted to
      determine U(VI) adsorption on gravel, because of presence of Fe oxides coatings
      and diffusion-controlled adsorption into the gravel particles' interior surfaces.
      A linear adsorption isotherm was observed up to 10(-6) M (238 microg/L) of total
      U(VI) concentration in batch U(VI) adsorption tests with varying total U(VI)
      concentrations in spiked groundwater. U(VI) adsorption decreased with increasing
      concentrations of dissolved carbonate, because strong anionic aqueous uranium
      carbonate complexes formed at high pH and high alkalinity conditions. Noticeable
      uranium desorption hysteresis was observed in a flow-through column experiment,
      suggesting that desorption K(d) values for aged uranium-contaminated sediments at
      the Hanford Site can be larger than adsorption K(d) values determined in short
      term laboratory experiments and slow uranium release from contaminated sediments
      into the groundwater is expected.

PMID- 17499880
TI  - TGF-beta superfamily signaling is essential for tooth and hair morphogenesis and
      differentiation.
AB  - Members of the transforming growth factor beta (TGF-beta) superfamily of
      signaling molecules are involved in the regulation of many developmental
      processes that involve the interaction between mesenchymal and epithelial
      tissues. Smad7 is a potent inhibitor of many members of the TGF-beta family,
      notably TGF-beta and activin. In this study, we show that embryonic
      overexpression of Smad7 in stratified epithelia using a keratin 5 promoter,
      results in severe morphogenetic defects in skin and teeth and leads to embryonic
      and perinatal lethality. To further analyze the functions of Smad7 in epithelial
      tissues of adult mice, we used an expression system that allowed a controlled
      overexpression of Smad7 in terms of both space and time. Skin defects in adult
      mice overexpressing Smad7 were characterized by hyper-proliferation and missing
      expression of early markers of keratinocyte differentiation. Upon Smad7-mediated
      blockade of TGF-beta superfamily signaling, ameloblasts failed to produce an
      enamel layer in incisor teeth. In addition, TGF-beta blockade in adult mice
      altered the pattern of thymic T cell differentiation and the number of thymic T
      cells was significantly reduced. This study shows that TGF-beta superfamily
      signaling is essential for development of hair, tooth and T-cells as well as
      differentiation and proliferation control in adult tissues.

PMID- 17499881
TI  - Ancordin, the major rhizome protein of madeira-vine, with trypsin inhibitory and
      stimulatory activities in nitric oxide productions.
AB  - Anredera cordifolia (Ten.) Steenis, or the synonymous name of Boussingaultia
      baselloides or Boussingaultia gracilis var. pseudobaselloides, is a South
      American species of ornamental succulent vine, commonly known as the madeira
      vine. The fresh leaves of madeira-vine are frequently used as vegetables. A.
      cordifolia is an evergreen climber that grows from fleshy rhizomes. The rhizome
      contained one major (23kDa) protein band under non-reducing condition in the SDS
      PAGE. The first 15 amino acids in the N-terminal region of the major protein band
      (23kDa), named tentatively ancordin, were KDDLLVLDIGGNPVV which were highly
      homologous to sequences of winged bean seed protein ws-1, Medicago truncatula
      proteinase inhibitor, soybean trypsin inhibitor, and sporamin. By using activity
      stains, the ancordin showed trypsin inhibitory activity in the SDS-PAGE gel which
      was found not only in rhizomes but also in aerial tubers, but few in fresh
      leaves. The crude extracts from rhizomes of madeira-vine were directly loaded
      onto trypsin-Sepharose 4B affinity column. After washing with 100mM Tris-HCl
      buffer (pH 7.9) containing 100mM NaCl, the ancordin was eluted directly by 0.2M
      KC1-HC1 buffer (pH 2.0). In calculation, the purified protein exhibited 0.0428mug
      trypsin inhibition/mug ancordin (corresponding to 0.53 unit of TPCK-treated
      trypsin inhibited/mug ancordin). The purified ancordin was used to evaluate the
      nitric oxide productions in RAW264.7 cells in the presence of polymyxin B (poly
      B, 50microg/ml) to eliminate the lipopolysaccharide (LPS) contaminations. It was
      found that ancordin (1.25-5microg/ml) could dose-dependently (R=0.954) stimulate
      the nitric oxide (NO) productions (expressed as nitrite concentrations) in
      RAW264.7 cells without significant cytotoxicity, and kept the similar effects in
      NO production in 6.25microg/ml ancordin.

PMID- 17499882
TI  - Altered anxiety-related behavior in nociceptin/orphanin FQ receptor gene knockout
      mice.
AB  - Studies showed that nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP)
      agonists produce anxiolytic-like actions, while little is known about the effects
      of blockade of NOP receptor signaling in anxiety. To this aim, we investigated
      the behavioral phenotype of NOP receptor gene knockout mice (NOP(-/-)) in
      different assays. In the elevated plus-maze and light-dark box, NOP(-/-) mice
      displayed increased anxiety-related behavior. In the novelty-suppressed feeding
      behavior and elevated T-maze, NOP(-/-) mice showed anxiolytic-like phenotype,
      while no differences were found in the open-field, hole-board, marble-burying,
      and stress-induced hyperthermia. Altogether, these findings suggest that the
      N/OFQ-NOP receptor system modulates anxiety-related behavior in a complex manner.

PMID- 17499883
TI  - Calorie restriction ameliorates neurodegenerative phenotypes in forebrain
      specific presenilin-1 and presenilin-2 double knockout mice.
AB  - Conditional double knockout of presenilin-1 and presenilin-2 (cDKO) in forebrain
      of mice led to brain atrophy, tau hyperphosphorylation, synaptic dysfunction and
      cognitive deficit. These brain changes recapitulated most of the
      neurodegenerative phenotypes of Alzheimer's disease (AD). In this report, we have
      investigated the effects of 4-month calorie restriction (CR) regimen on different
      phenotypes in cDKO mice. We found that CR improved novel object recognition and
      contextual fear conditioning memory in the cDKO mice. Histological and
      biochemical analysis showed that CR attenuated ventricle enlargement, caspase-3
      activation and astrogliosis. In addition, the induction of tau
      hyperphosphorylation in the cDKO mice was reduced by CR, possibly through
      reduction of p25 accumulation and aberrant CDK5 activation. Finally, DNA
      microarray analysis demonstrated that CR could increase the expression of
      neurogenesis related genes and decrease the expression of inflammation related
      genes in the hippocampus of cDKO mice. The possible molecular mechanisms of the
      CR effects on alleviating AD pathogenesis have been discussed.

PMID- 17499884
TI  - Characterization of Japanese-American men with a single neocortical AD lesion
      type.
AB  - Neocortical neuritic plaques (NP) and neurofibrillary tangles (NFT) are hallmarks
      of Alzheimer's disease (AD) and usually, both are present. The Honolulu-Asia
      Aging Study autopsy series includes a significant number of individuals with only
      one neocortical AD lesion type. These could represent an early phase of the AD
      process. If so, such individuals would be expected to share other clinical and
      pathological features of AD. We compared frequency of apolipoprotein epsilon E4
      (APOE4) allele, average Braak stage, and burden of cerebral amyloid angiopathy
      (CAA) among the two single lesion type groups, a group without AD lesions, and
      groups with high and low frequencies of both AD lesions. Single AD lesion groups
      shared only the characteristics associated with their unique lesion type with the
      combined AD lesion group and did not have higher prevalence of dementia than the
      no AD lesion group. Only the NP+NFT group showed a "dose-response" relationship
      with greater probability of dementia with higher neocortical frequencies of
      either AD lesion. The single neocortical AD lesion groups do not appear to
      represent early AD.

PMID- 17499885
TI  - Cytotoxic 3,5-bis(benzylidene)piperidin-4-ones and N-acyl analogs displaying
      selective toxicity for malignant cells.
AB  - A series of 3,5-bis(benzylidene)piperidin-4-ones 1, 1-acryloyl-3,5
      bis(benzylidene)piperidin-4-ones 2 and adducts of 2 with sodium 2
      mercaptoethanesulfonate (mesna), namely series 3, were prepared as candidate
      cytotoxic agents. These compounds were examined against neoplastic HSC-2, HSC-4
      and HL-60 cells as well as HGF, HPC and HPLF normal cell lines and many of the
      compounds displayed selective toxicity for malignant cells. The CC50 values of
      the analogs in series 2 towards the cancer cell lines were mainly submicromolar.
      The relative potencies, selectivity and logP values were in the order of 2>1>3.
      The sulfonic acid group of a representative compound in series 3 was replaced by
      a thiol function to produce 4 leading to substantial increases in cytotoxic
      potencies and hydrophobicity indicating that the presence of a hydrophilic
      sulfonic acid group was disadvantageous in terms of potency. Molecular modeling
      suggested that the superior cytotoxicity of various members of series 1-3 over an
      acyclic analog 5 may have been due to the greater torsion angles theta1 and
      theta2 created between the arylidene aryl rings and the adjacent olefinic groups
      in series 1-3.

PMID- 17499886
TI  - Chemoenzymatic synthesis and antimicrobial activity evaluation of monogalactosyl
      diglycerides.
AB  - Monogalactosyl diglycerides with medium to long fatty acid acyl chains, were
      prepared and examined for antimicrobial activity against Gram positive, Gram
      negative bacteria and fungi. The study of their in vitro antimicrobial activity
      confirms the significant activity of some monogalactosyl diacylglycerol analogues
      and establishes for the galactose series that the 1,2-disubstitution and the
      octanoyl chain are the proper structural features for the maximum activity.

PMID- 17499887
TI  - New triazole and triazolothiadiazine derivatives as possible antimicrobial
      agents.
AB  - Triazole and triazoles fused with six-membered ring systems are found to possess
      diverse applications in the fields of medicine, agriculture and industry. The new
      1,2,4-triazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives were
      synthesized as novel antimicrobial agents. The reaction of 1H-indol-3-acetic acid
      with thiocarbohydrazide gave the 4-amino-3-mercapto-5-[(1H-indol-3-yl)methyl]-4H
      1,2,4-triazole. The reaction of triazole with arylaldehydes in ethanol gave the 4
      arylideneamino-3-mercapto-5-[(1H-indol-3-yl)methyl]-4H-1,2,4-triazoles (I). The 3
      [(1H-indol-3-yl)methyl]-6-aryl-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines (II)
      were obtained by condensing triazole with phenacyl bromides in absolute ethanol .
      The chemical structures of the compounds were elucidated by IR, (1)H NMR and
      FAB(+)-MS spectral data. Their antimicrobial activities against Micrococcus
      luteus (NRLL B-4375), Bacillus cereus (NRRL B-3711), Proteus vulgaris (NRRL B
      123), Salmonella typhimurium (NRRL B-4420), Staphylococcus aureus (NRRL B-767),
      Escherichia coli (NRRL B-3704), Candida albicans and Candida glabrata (isolates
      obtained from Osmangazi University, Faculty of Medicine) were investigated and
      significant activity was obtained.

PMID- 17499888
TI  - Carbamate prodrugs of N-alkylfuramidines.
AB  - The synthesis and evaluation of 2,5-bis[4-(N-ethoxycarbonyl-N'
      isopropyl)amidinophenyl]furan, 2,5-bis[4-(N-2,2,2-trichloroethoxycarbonyl-N'
      isopropyl)amidinophenyl]furan and 2,5-bis[4-(N-cyclopentyl-N'-2,2,2
      trichloroethoxycarbonyl)amidinophenyl]furan as prodrugs of bis-N-alkylamidines
      are reported. The results show that the bis-2,2,2-trichloroethyl carbamates
      function effectively in a rat model for Pneumocystis pneumonia.

PMID- 17499889
TI  - Identification of 1-isopropylsulfonyl-2-amine benzimidazoles as a new class of
      inhibitors of hepatitis B virus.
AB  - A series of 1-isopropylsulfonyl-2-amine benzimidazole derivatives were
      synthesized and evaluated for their anti-hepatitis B virus (HBV) activity and
      cytotoxicity in the HepG2.2.15 cell line. In general, these derivatives are
      potent HBV inhibitors (IC(50)<4 microM) with high selectivity indices (SIs>40).
      Compounds 5b-e, g, j, and 9a were among the most prominent compounds, with
      IC(50)s of 0.70-2.0 microM and SIs of 41-274. The potent anti-HBV activity and
      safety profiles of the most promising compounds 5d and j (IC(50)s=0.70 microM,
      SIs>120) demonstrate the potential of this series of benzimidazoles for the
      development of new anti-HBV drugs.

PMID- 17499890
TI  - [Inappropriate ADH secretion-induced hyponatremia and associated with paroxetine
      use].
AB  - INTRODUCTION: Selective serotonin reuptake inhibitors (SSRI) are the most common
      antidepressants prescribed for elderly people. Although they are generally better
      tolerated than other antidepressant treatment classes, they can be responsible
      for potentially life-threatening hyponatremia, related to syndrome of
      inappropriate antidiuretic hormone secretion (SIADH). OBSERVATION: A 64 years-old
      woman was hospitalized for cognitive function alteration and vomiting after
      introduction of paroxetine for depressive symptoms. Serum investigations revealed
      hyponatremia (121 mmol/l) with low plasma osmolarity and normal natriuria
      consistent with diagnosis of SIADH. Hyponatremia was reversible after paroxetine
      withdrawal. DISCUSSION: Hyponatremia induced by SIADH is a serious but
      underestimated complication of SSRI treatment. This complication occurs in the
      elderly people within the first month of treatment. Monitoring of the serum
      sodium concentration during the first month of treatment is recommended for older
      patients.

PMID- 17499891
TI  - Environmental lead toxicity and nutritional factors.
AB  - Environmental lead toxicity is an old but persistent public health problem
      throughout the world and children are more susceptible to lead than adults
      because of their hand to mouth activity, increased respiratory rates and higher
      gastrointestinal absorption per unit body weight. In the last decade children's
      blood lead levels have fallen significantly in a number of countries. Despite
      this reduction, childhood lead toxicity continues to be a major public health
      problem for certain at-risk groups of children, and concern remains over the
      effects of lead on intellectual development. The currently approved clinical
      intervention method is to give chelating agents, which bind and removed lead from
      lead burdened tissues. Studies indicate, however, that there is a lack of safety
      and efficacy when conventional chelating agents are used. Several studies are
      underway to determine the beneficial effect of nutrients supplementation
      following exposure to lead. Data suggest that nutrients may play an important
      role in abating some toxic effects of lead. To explain the importance of using
      exogenous nutrients in treating environmental lead toxicity the following topics
      are addressed: (i) different sources of lead exposure/current blood lead levels
      and (ii) protective effects of nutrients supplementation (some essential elements
      and vitamins) in lead toxicity.

PMID- 17499892
TI  - A randomized trial on the efficacy of a 2-month tube feeding regimen in anorexia
      nervosa: A 1-year follow-up study.
AB  - BACKGROUND & AIMS: Despite the high mortality rate in malnourished anorexia
      nervosa (AN) patients, very few trials have prospectively studied the efficacy of
      tube feeding. METHODS: This open prospective study was conducted in malnourished
      AN patients, who were randomized in tube feeding (n=41) or control (n=40) groups
      during a 2-month period. Thereafter, body weight, body mass gain, energy intake,
      eating behavior and relapse rates were compared during a 1-year follow-up, using
      paired Student t-test and ANOVA. RESULTS: At the end of the 2-months period,
      weight gain was 39% higher in the tube feeding group than in the control group
      (194+/-14 vs 126+/-19g/day; P<0.01). The fat-free mass gain was greater in the
      tube-feeding group: 109+/-14 vs 61+/-17g/day (P<0.01). Energy intake was higher
      in the tube feeding group than in the control group (P<0.05), as well as the
      decrease in bingeing episodes (P<0.01). Most patients thought that CEN improved
      their eating disorder. After discharge, the relapse-free period was longer in the
      CEN group than in the control one: 34.3+/-8.2 weeks vs 26.8+/-7.5 weeks (P<0.05).
      CONCLUSION: CEN is helpful in malnourished AN patients for weight restoration,
      without hindrance on the eating behavior therapy nor inducing a more rapid
      relapse.

PMID- 17499894
TI  - Use of a safety tie in the placement of miniscrews.

PMID- 17499893
TI  - Vaccination with recombinant modified vaccinia virus Ankara expressing bovine
      respiratory syncytial virus (bRSV) proteins protects calves against RSV
      challenge.
AB  - Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease
      in infants and calves. Bovine RSV (bRSV) is a natural pathogen for cattle, and
      bRSV infection in calves shares many features with the human infection. Thus,
      bRSV infection in cattle provides the ideal setting to evaluate the safety and
      efficacy of novel RSV vaccine strategies. Here, we have evaluated the efficacy
      and safety of modified vaccinia virus Ankara (rMVA)-based vaccine candidates,
      expressing the bovine RSV-F protein, either or not in combination with the G
      protein, in colostrums-deprived SPF calves born by caesarean section. Vaccination
      induced bRSV-specific IgG and CD8 T cell responses. Importantly, no IgE responses
      were detected. After bRSV challenge, rMVA vaccinated calves experienced less
      severe symptoms of lower respiratory tract disease compared to the mock-immunized
      control group. Immunized animals showed reduced pulmonary virus loads, and no
      eosinophilic infiltration or enhanced respiratory distress. In conclusion,
      candidate rMVA/bRSV vaccines induced protective and safe immune responses in
      calves.

PMID- 17499895
TI  - Past and present midwifery education in Turkey.
AB  - Among criteria relating to the level of development in a country are health
      indicators such as total fertility, maternal mortality, infant mortality, and
      rates of life expectancy at birth. These have a close relationship with the
      quality of health-care services, especially those provided by midwives. An
      improvement in midwifery services can be achieved to a great extent by
      standardised and high-quality midwifery education. Until recently, midwifery
      education has not been standardised in Turkey. Although improvements have been
      made, more needs to be accomplished. In this paper, we report the development of
      midwifery education in Turkey from a historical perspective, dealing with past
      and present applications, and make recommendations to overcome existing problems.

PMID- 17499896
TI  - Sex differences in lower extremity biomechanics during single leg landings.
AB  - BACKGROUND: Females have an increased incident rate of anterior cruciate ligament
      tears compared to males. Biomechanical strategies to decelerate the body in the
      vertical direction have been implicated as a contributing cause. This study
      determined if females would exhibit single leg landing strategies characterized
      by decreased amounts of hip, knee, and ankle flexion resulting in greater
      vertical ground reaction forces and altered energy absorption patterns when
      compared to males. METHODS: Recreationally active males (N=14) and females
      (N=14), completed five single leg landings from a 0.3m height onto a force
      platform while three-dimensional kinematics and kinetics were simultaneously
      collected. FINDINGS: Compared to males, females exhibited (1) less total hip and
      knee flexion displacements (40% and 64% of males, respectively, P<0.05) and less
      time to peak hip and knee flexion (48% and 78% of males, respectively, P<0.05),
      (2) 9% greater peak vertical ground reaction forces (P<0.05), (3) less total
      lower body energy absorption (76% of males, P<0.05), and (4) 11% greater relative
      energy absorption at the ankle (P<0.05). INTERPRETATION: Females in this study
      appear to adopt a single leg landing style using less hip and knee flexion,
      absorbing less total lower body energy with more relative energy at the ankle
      resulting in a landing style that can be described as stiff. This may potentially
      cause increased demands on non-contractile components of the lower extremity.
      Preventative training programs designed to prevent knee injury may benefit from
      the biomechanical description of sex-specific landing methods demonstrated by
      females in this study by focusing on the promotion of more reliance on using the
      contractile components to absorb impact energy during landings.

PMID- 17499897
TI  - Regulating endocrine disruptors.

PMID- 17499898
TI  - 'Am I normal?' Teenagers, sexual health and the internet.
AB  - The development of new communication technologies has created a wide variety of
      new fields in which human beings can construct identities. The past decade has
      seen a proliferation of opportunities to use the internet for health related
      advice and information and many new sites have been created where participants
      can construct identities, formulate problems and seek solutions concerning health
      related issues. This paper will report on a study of emails written in to a UK
      based website concerned with health issues for young people. Our analysis was
      driven by corpus linguistics, a computational methodology for interrogating
      extensive datasets, and we have combined both quantitative and qualitative
      approaches to the study of language. We interrogated a 400,000 word dataset of
      messages and were able to identify terms whose usage was elevated compared to the
      English language as a whole. As well as personal pronouns, these included many
      terms related to sexual health and bodily development, as well as terms such as
      'normal' and 'worried' which were identified for further exploration. Whereas
      previous research on sexual health has discovered the use of vague terms and
      euphemisms, here, young people described themselves, their anatomy and their
      identities in meticulous detail. This study enables us to define the role of
      health topics raised, the presentation of health concerns, and contributes
      towards the discovery of a distinctive 'genre' of health messages concerning
      sexual health which differs from that found by other researchers concentrating on
      face to face encounters. In conclusion we suggest that for researchers and
      practitioners working in health with young people in the medium of English there
      could be valuable lessons in communication to be learned from examination of
      corpora of the health care language concerned.

PMID- 17499899
TI  - Understanding differences in past year psychiatric disorders for Latinos living
      in the US.
AB  - This study seeks to identify risk factors for psychiatric disorders that may
      explain differences in nativity effects among adult Latinos in the USA. We
      evaluate whether factors related to the processes of acculturation and
      enculturation, immigration factors, family stressors and supports, contextual
      factors, and social status in the US account for differences in 12-month
      prevalence of psychiatric disorders for eight subgroups of Latinos. We report
      results that differentiate Latino respondents by country of origin and age at
      immigration (whether they were US-born or arrived before age 6: In-US-as-Child
      [IUSC]; or whether they arrived after age 6: later-arrival immigrants [LAI]).
      After age and gender adjustments, LAI Mexicans and IUSC Cubans reported a
      significantly lower prevalence of depressive disorders than IUSC Mexicans. Once
      we adjust for differences in family stressors, contextual factors and social
      status factors, these differences are no longer significant. The risk for anxiety
      disorders appears no different for LAI compared to IUSC Latinos, after age and
      gender adjustments. For substance use disorders, family factors do not offset the
      elevated risk of early exposure to neighborhood disadvantage, but coming to the
      US after age 25 does offset it. Family conflict and burden were consistently
      related to the risk of mood disorders. Our findings suggest that successful
      adaptation into the US is a multidimensional process that includes maintenance of
      family harmony, integration in advantageous US neighborhoods, and positive
      perceptions of social standing. Our results uncover that nativity may be a less
      important independent risk factor for current psychiatric morbidity than
      originally thought.

PMID- 17499900
TI  - Rethinking social recovery in schizophrenia: what a capabilities approach might
      offer.
AB  - Resurgent hopes for recovery from schizophrenia in the late 1980s had less to do
      with fresh empirical evidence than with focused political agitation. Recovery's
      promise was transformative: reworking traditional power relationships, conferring
      distinctive expertise on service users, rewriting the mandate of public mental
      health systems. Its institutional imprint has been considerably weaker. This
      article takes sympathetic measure of that outcome and provides an alternative
      framework for what recovery might mean, one drawn from disability studies and
      Sen's capabilities approach. By re-enfranchising agency, redressing material and
      symbolic disadvantage, raising the bar on fundamental entitlements and claiming
      institutional support for complex competencies, a capabilities approach could
      convert flaccid doctrine into useful guidelines and tools for public mental
      health.

PMID- 17499901
TI  - Dexamethasone protects RAW264.7 macrophages from growth arrest and apoptosis
      induced by H2O2 through alteration of gene expression patterns and inhibition of
      nuclear factor-kappa B (NF-kappaB) activity.
AB  - In this study, the effect of dexamethasone, a synthetic glucocorticoid, on
      H(2)O(2) stimulated murine RAW264.7 macrophages was investigated. It was found
      that dexamethasone protected the cells from apoptosis induced by H(2)O(2). A cDNA
      microarray, which consists of 1000 genes selected from a mouse clone set provided
      from NIA, was used to study the gene expression profiles involved in the
      protective effect. Our data show that dexamethasone exerts the anti-apoptosis
      function by changing the expression patterns of many genes involved inhibiting
      the up-regulation of apoptosis promoting genes and the down-regulation of cell
      cycle stimulating genes as well as keeping the up-regulation of cell survival
      related genes. Our study also revealed that dexamethasone protects RAW264.7
      macrophages from H(2)O(2) induced apoptosis through blocking nuclear factor-kappa
      B (NF-kappaB) activity.

PMID- 17499902
TI  - Diazinon immunotoxicity in mice: modulation of cytokines level and their gene
      expression.
AB  - Diazinon is one of the organophosphate pesticides of wide spectrum insect-killing
      power. Diazinon extensive application as an effective pesticide was associated
      with direct or indirect modulation of major and vital immune mechanisms. This
      study addressed the effect of diazinon toxicity on cytokines that are involved in
      the regulation of innate, cellular and humoral immune responses. Mice intoxicated
      with 50 mg/kg (1/5 LD50) body weight for 30 days indicated gradual decrease in
      the level of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10),
      interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) in the splenocytes
      cultures that were pulsed with phytohaemagglutinin (PHA). Sever suppression of
      these cytokines was confirmed by the RT-PCR. The level of IL-10 in CD4(+),
      CD8(+), and B cells indicated significant increase, whereas INF-gamma level was
      significantly decreased in B cells only. On the molecular level, the INF-gamma
      mRNA synthesis was significantly increased in all cells subpopulation, whereas,
      IL-2 mRNA synthesis was only increased in CD4(+). It was shown that diazinon
      immunotoxicity in mice capable of modulating the major cytokines involved in the
      regulation of the immune responses. In certain stage of diazinon toxicity, Th2
      type responses appeared dominant. Diazinon could accelerate the INF- gamma and IL
      2 mRNA synthesis but their translation might be impaired.

PMID- 17499903
TI  - Risk assessment of topically applied products.
AB  - The human risk of harmful substances in semisolid topical dosage forms applied
      topically to normal skin and broken skin, respectively, was assessed. Bisphenol A
      diglycidyl ether (BADGE) and three derivatives of BADGE previously quantified in
      aqueous cream and the UV filters 3-BC and 4-MBC were used as model compounds.
      Tolerable daily intake (TDI) values have been established for BADGE and
      derivatives. Endocrine disruption was chosen as endpoint for 3-BC and 4-MBC. Skin
      permeation of the model compounds was investigated in vitro using pig skin
      membranes. Tape stripping was applied to simulate broken skin associated with
      various skin disorders. BADGE and derivatives had a tendency to permeate pig skin
      membranes in vitro with higher fluxes in the tape stripped membranes compared to
      the non-treated membranes. Data from the in vitro skin permeation study and from
      the literature were used as input parameters for estimating the risk. The
      immediate human risk of BADGE and derivatives in topical dosage forms was found
      to be low. However, local treatment of broken skin may lead to higher exposure of
      BADGE and derivatives compared to application to normal skin. 3-BC permeated skin
      at higher flux than 4-MBC. Both UV filters are endocrine disrupting compounds
      with 3-BC being the more potent. UV filters in sunscreen are often present in
      high concentrations, which potentially may lead to high systemic exposure
      dosages. Thus, the risk associated with use of 3-BC and 4-MBC containing
      sunscreen with regards to endocrine disrupting effects was found to be high and
      more data is urgently needed in order to fully assess the human risk of 3-BC and
      4-MBC in commercial sunscreen.

PMID- 17499904
TI  - Resuscitation great. The Holger Nielsen method of artificial respiration.

PMID- 17499905
TI  - The State Research Institute of General Reanimatology, Russian Academy of Medical
      Sciences, is 70 years old.

PMID- 17499906
TI  - A PET study of regional cerebral blood flow after experimental cardiopulmonary
      resuscitation.
AB  - Cerebral blood flow (CBF) during cardiopulmonary resuscitation and after
      restoration of spontaneous circulation (ROSC) from cardiac arrest has previously
      been measured with the microspheres and laser Doppler techniques. We used
      positron emission tomography (PET) with [15O]--water to map the haemodynamic
      changes after ROSC in nine young pigs. After the baseline PET recording,
      ventricular fibrillation of 5 min duration was induced, followed by closed-chest
      cardiopulmonary resuscitation (CPR) in conjunction with IV administration of
      three bolus doses of adrenaline (epinephrine). After CPR, external defibrillatory
      shocks were applied to achieve ROSC. CBF was measured at intervals during 4h
      after ROSC. Relative to the mean global CBF at baseline (32+/-5 ml hg(-1)min(
      1)), there was a substantial global increase in CBF at 10 min, especially in the
      diencephalon. This was followed by an interval of cortical hypoperfusion and a
      subsequent gradual return to baseline values.

PMID- 17499907
TI  - Performance of an overland flow system for advanced treatment of wastewater plant
      effluent.
AB  - Overland flow (OF) systems were evaluated and compared for advanced treatment of
      municipal and industrial effluents, including nutrients and nondegradable
      chemical oxygen demand (COD) removal. Three pilot plants were constructed at the
      Shahin Shahr Wastewater Treatment Plant (WWTP), Isfahan, Iran. Each pilot was
      assigned a specific wastewater and all were simultaneously operated for 8 months.
      Treatment of primary effluent, activated sludge secondary effluent, and lagoon
      effluent of textile wastewater was investigated at application rates (ARs) of
      0.15, 0.25, and 0.35 m(3)m(-1)h(-1). During 5 months of stable operation after a
      3-month acclimation period, mean removals of total 5-day biochemical oxygen
      demand (TBOD(5)), total COD (TCOD), total suspended solids (TSS), total nitrogen
      (TN), total phosphorus (TP) and turbidity were 74.5%, 54.8%, 66.2%, 39.4%, 35.8%,
      and 67.7% for primary effluent; 52.9%, 52.9%, 66.5%, 44.4%, 39.8%, and 50.1% for
      activated sludge effluent; 65.7%, 58.7%, 70.3%, 41.7%, 41.3%, and 54.9% for
      textile wastewater lagoon effluent, respectively. The model of Smith and
      Schroeder, 1985. Field studies of the overland flow process for the treatment of
      raw and primary treated municipal wastewater. Journal of Water Pollution Control
      Federation 57, 785-794] was satisfactory for TBOD(5). For all treatment
      parameters a standard first-order removal model was inadequate to represent the
      data but a modified first-order model provided a satisfactory fit to the data.
      Based on the results of this study, it can be concluded that an OF system as
      advanced treatment had the ability to meet effluent discharge permit limits and
      was an economical replacement for stabilization ponds and mechanical treatment
      options.

PMID- 17499908
TI  - Groundwater risk assessment at a heavily industrialised catchment and the
      associated impacts on a peri-urban wetland.
AB  - Industrial and agricultural activities often impose significant pressures to the
      groundwater quality and consequently degrade wetland ecosystems that depend
      mostly on subsurface water flow. Groundwater vulnerability and risk mapping is a
      widely used approach to assess the natural protection of aquifers and the
      associated pollution potential from human activities. In the particular study,
      the relatively new Pan-European methodology (COP method) has been applied in a
      highly industrialized peri-urban wetland catchment, located close to Athens city,
      to map the intrinsic vulnerability of the aquifer and evaluate the risk potential
      originating from local land uses. Groundwater analysis results for various
      parameters, including Phenols, PCBs and nutrients, have been used to validate the
      vulnerability and risk estimations while a biological assessment occurred to
      associate the mapping results with the wetland's ecological status. The results
      indicated that even though the natural protection of the aquifer is relatively
      high due to the dominant hydrogeologic and geomorphologic conditions, the
      groundwater pollution risk is considerable, mainly because of the existing
      hazardous land uses. The water quality of the groundwater accredited these
      findings and the ecological status of this peri-urban wetland also indicated
      significant impacts from industrial effluents.

PMID- 17499909
TI  - Assessing the ecosystem service of air pollutant removal by urban trees in
      Guangzhou (China).
AB  - In Chinese cities, air pollution has become a serious and aggravating
      environmental problem undermining the sustainability of urban ecosystems and the
      quality of urban life. Besides technical solutions to abate air pollution, urban
      vegetation is increasingly recognized as an alternative ameliorative method by
      removing some pollutants mainly through dry deposition process. This paper
      assesses the capability and monetary value of this ecosystem service in Guangzhou
      city in South China. The results indicated an annual removal of SO(2), NO(2) and
      total suspended particulates at about 312.03 Mg, and the benefits were valued at
      RMB90.19 thousand (US$1.00=RMB8.26). More removal was realized by recreational
      land use due to a higher tree cover. Higher concentration of pollutants in the
      dry winter months induced more removal. The lower cost of pollution abatement in
      China generated a relatively subdued monetary value of this environmental benefit
      in comparison with developed countries. Younger districts with more extensive
      urban trees stripped more pollutants from the air, and this capacity was
      anticipated to increase further as their trees gradually reach final dimensions
      and establish a greater tree cover. Tree cover and pollutant concentration
      constitute the main factors in pollutant removal by urban trees. The efficiency
      of atmospheric cleansing by trees in congested Chinese cities could be improved
      by planting more trees other than shrubs or grass, diversifying species
      composition and biomass structure, and providing sound green space management.
      The implications for greenery design were discussed with a view to maximizing
      this ecosystem service in Chinese cities and other developing metropolises.

PMID- 17499910
TI  - Post-tsunami changes in the littoral environment along the southeast coast of
      India.
AB  - The 26th December 2004 Indian Ocean tsunami devastated coastal regions of the
      Indian subcontinent. Andaman and Nicobar Islands, coastal stretches of Tamil
      Nadu, Andhra Pradesh and Kerala were the most affected regions of India. Changes
      in the beach profiles, long shore currents, breaking wave characteristics in the
      surf zone at selected locations along the Tamil Nadu coast were studied during
      January, April, October 2005 and January 2006. Long shore sediment transport
      rates were estimated from the observed parameters. Studies were carried out
      earlier (1995-1996 and 1998) to understand the coastal environment over a one
      year cycle in the study region. The post-tsunami observations were compared with
      the earlier studies to establish the variations in the littoral environment and
      to ascertain the normalcy of the littoral environment in the post-tsunami
      scenario. From the changes in the beach profiles, the shoreline was observed to
      recede by about 20 m and built-up of backshore by about 0.5 m at most locations.
      Observations from the field investigations and comparisons with earlier studies
      along this stretch of the coastline indicate that the coastline is yet to return
      completely to normalcy.

PMID- 17499911
TI  - Editorial comment on: Optimizing shock wave lithotripsy in the 21st century.

PMID- 17499912
TI  - Editorial comment on: Optimizing shock wave lithotripsy in the 21st century.

PMID- 17499913
TI  - Ceteris paribus and nomograms in medicine.

PMID- 17499914
TI  - Optimizing shock wave lithotripsy in the 21st century.
AB  - OBJECTIVE: Shock wave lithotripsy (SWL) has radically changed treatment of stone
      disease and appears to be the first option for the majority of patients. This
      review of current literature focused on suggestions for optimising technique,
      patient selection, results, and lithotriptor comparison for SWL. METHODS:
      Literature search for SWL was performed for recently published papers in English
      language. Topics of interest were treatment protocols; patient evaluation; pre
      SWL prediction of outcome; lithotriptor technology; efficacy; and methods to
      assess the effects, decrease complications, and compare lithotriptors. Earlier
      classic papers on SWL and guidelines for stone disease were also reviewed.
      RESULTS: Recent literature contained important recommendations about SWL
      concerning (1) methods to predict stone fragmentation; (2) identification of
      factors contributing to treatment failure for lower pole and ureteric calculi;
      (3) guidelines from urological associations; (4) manoeuvres and changes in SWL
      delivery (slower rate, twin-pulse technique) to increase efficacy and decrease
      complications; (5) clarification of the role of medical treatment (antibiotics,
      alpha-blockers); (6) role of SWL in calyceal stones, CIRF, and abnormal kidneys;
      (7) obesity and SWL; and (8) methods to evaluate and compare lithotriptors.
      CONCLUSIONS: SWL delivered in an outpatient setting as an anaesthesia-free
      treatment is still considered the first option for the majority of stones with a
      minimal number of complications. Better understanding of the physics of shockwave
      delivery is required, together with treatment optimisation by limiting renal
      damage and better selection of patients because this approach will offer maximum
      benefit to patients and physicians, as well as more cost-effective treatment.

PMID- 17499916
TI  - Extraction and separation of Pd(II), Pt(IV), Fe(III), Zn(II), Cu(II) and Ag(I)
      from hydrochloric acid solutions with selected cyanamides as novel extractants.
AB  - Three structurally related novel extractants namely: N,N-dihexylcyanamide (DHCY),
      N,N-di(2-ethylhexyl)cyanamide (DEHCY) and N,N-di-octylcyanamide (DOCY) were
      synthesized in our laboratory and characterized by different techniques. The
      general method for synthesizing these extractants was based on the reaction of
      relevant secondary amines with cyanogen bromide in presence of sodium acetate
      anhydride. Their extracting ability in toluene as a diluent for Pd(II), Pt(IV),
      Fe(III), Zn(II), Cu(II) and Ag(I) from hydrochloric acid media has been studied.
      The extraction of hydrochloric acid was studied also. Pd(II) was strongly
      extracted by these extractants at low hydrochloric acid concentrations and the
      extraction decreased with increasing hydrochloric acid concentration while the
      reverse was obtained in the extraction of Pt(IV), Fe(III) and Zn(II). Under
      similar extraction conditions Cu(II) and Ag(I) were found poorly extracted.
      Hydrochloric acid was extracted only in its high concentration region. A
      systematic investigation has been carried out on the extraction of Pd(II) using
      two of the synthesized extractants. Pd(II) was extracted as a solvated complex
      with the composition, metal:chloride ion:extractant=1:2:2. The extracted species
      were studied also using IR spectra.

PMID- 17499915
TI  - Identification of arsenic-binding proteins in human breast cancer cells.
AB  - As a cancer chemotherapeutic drug, arsenic acts on numerous intracellular signal
      transduction pathways in cancer cells. However, its mechanism of actions is still
      not fully understood. Previous studies suggest that arsenic reacts with closely
      spaced cysteine (Cys) residues of proteins with high Cys content and accessible
      sulfhydryl (SH) groups. In this study, human breast cancer cell line MCF-7 was
      examined as a cellular model to explore arsenic-binding proteins and the
      mechanism of binding. An arsenic-biotin conjugate was synthesized by coupling the
      pentafluorophenol ester of biotin with p-aminophenylarsenoxide. Arsenic-binding
      proteins were eluted with streptavidin resin from arsenic-biotin treated MCF-7
      cells, separated by polyacrylamide gel electrophoresis, and identified by matrix
      assisted laser desorption ionization mass spectrometry (MALDI-MS). Arsenic
      binding properties of two of these proteins, beta-tubulin and pyruvate kinase M2
      (PKM2), were studied further in vitro and the biological consequences of this
      binding was evaluated. Binding assay with Western blotting confirmed binding of
      beta-tubulin and PKM2 by arsenic in a concentration-dependent manner. Arsenic
      binding inhibited tubulin polymerization, but surprisingly had no effect on PKM2
      activity. Molecular modeling showed that binding of Cys(12) alone or vicinal Cys
      residues (Cys(12) and Cys(213)) of beta-tubulin by arsenic blocked the active
      site for access of GTP, which is necessary for tubulin polymerization. On the
      contrary, all Cys residues of PKM2 were far away from the active site of the
      enzyme. In summary, this study confirmed beta-tubulin and PKM2 as arsenic-binding
      proteins in MCF-7 cells. Functional consequence of such binding may depend on
      whether arsenic binding causes conformational changes or blocks active sites of
      target proteins.

PMID- 17499917
TI  - Effect of Pb-rich and Fe-rich entities during alteration of a partially vitrified
      metallurgical waste.
AB  - Lead blast furnace (LBF) slags are mainly composed of an iron-silica-lime glass
      matrix and minor phases such as solid solutions of Mg-Cr-rich and Fe-Zn-rich
      spinel crystals, crystallized iron oxides such as wustite and metallic lead
      droplets. In this study, results from Raman spectroscopy, transmission and
      scanning electron microscopy allow to argue that widely submicron iron-rich
      phases are very common in the glass matrix and could have an effect on the
      general alteration pattern of the glass matrix during leaching experiments. Open
      flow tests also point out close relationships between glass alteration ability
      and the presence of large lead droplets. According to numerous papers on nuclear
      glass leaching, acidic pH encountered in such open flow tests lead to
      preferential releases of the main alkali-earth metal composing the glass. Altered
      glass is mainly characterized by relative enrichments in iron. It is induced by
      high calcium or calcium-silicon depletions. Surprisingly, such type of alteration
      layer is not uniformly spread on the slag surface. In this work, it is also
      assumed that previous chemical analyses of the LBF glass matrix having
      micrometric resolution cannot give a realistic glass composition. A short
      discussion is also proposed about which characterization techniques can be used
      to correctly identify submicron iron-rich entities and evaluate their proportions
      and composition.

PMID- 17499918
TI  - Revealing characteristics of mixed consortia for azo dye decolorization: Lotka
      Volterra model and game theory.
AB  - This study provides a novel explanation to put forward, in Lotka-Volterra
      competition model and game theory, interspecific competition in bioaugmentation
      using constructed mixed consortia for azo dye decolorization. As mixed cultures
      are regularly used in industrial dye-laden wastewater treatment, understanding
      species competition of mixed consortia is apparently of great importance to azo
      dye decolorization. In aerobic growth conditions, Escherichia coli DH5alpha owned
      a growth advantage to out-compete Pseudomonas luteola due to preferential growth
      rate of DH5alpha. However, in static decolorization conditions DH5alpha
      surrendered some proportion of its advantage (i.e., a decrease in its competitive
      power for metabolite stimulation) to enhance color removal of P. luteola for
      total coexistence. In aerobic growth, DH5alpha had its growth advantage to
      exclude P. luteola for dominance (i.e, conflict strategy) according to
      competitive exclusion principle. In static decolorization conditions, as the
      removal of a common dye threat was crucial to both species for survival, both
      species selected cooperation strategy through metabolite stimulation of DH5alpha
      to enhance effective decolorization of P. luteola for long-term sustainable
      management. This analysis of game theory clearly unlocked unsolved mysteries in
      previous studies.

PMID- 17499919
TI  - Detoxification reactions of sulphur mustard on the surface of zinc oxide
      nanosized rods.
AB  - Detoxification reactions of sulphur mustard, a deadliest chemical warfare agent
      were studied on the surface of zinc oxide nanorods at room temperature (32+/-2
      degrees C) and the data was compared with that of the bulk ZnO. Prior to the
      reaction, the nanorods of zinc oxide were synthesized by the hydrothermal method
      and subsequently characterized by XRD, SEM, TG, N(2) BET, FT-IR. The data
      revealed the formation of nanorods with diameter ranging from 100 nm to 500 nm
      with length in microns. Obtained nanomaterial along with bulk ZnO were tested as
      reactive sorbent for the detoxification of sulphur mustard. Reaction was
      monitored by GC-FID technique and the reaction products were characterized by GC
      MS. Data explores the role of hydrolysis and elimination reactions in the
      detoxification of sulphur mustard and it also reveals that zinc oxide nanorods
      and bulk ZnO show the half lives of 8.48 h, 24.75 h in the first 12h and 122.47
      h, 177.29 h from 12h to 48 h of the reaction.

PMID- 17499920
TI  - Copper removal from aqueous solutions by sugar beet pulp treated by NaOH and
      citric acid.
AB  - Sugar beet pulp was converted into effective copper sorption material by treating
      subsequently with NaOH and citric acid. Compared with the untreated sugar beet
      pulp, the cation exchange capacity of the modified sugar beet pulp increased from
      0.86 to 3.21 mequiv.g(-1). Swelling capacity and COD values of modified sugar
      beet pulp were found to be decreased in the ratio of 38% and 61%, respectively,
      compared to the corresponding values of native sugar beet pulp, meaning that
      modification causes stabilization. Sorption characteristics of the modified sugar
      beet pulp towards copper ions were studied with batch experiments. Pseudo-first,
      pseudo-second-order and intraparticle kinetic models were applied to the kinetic
      data and it was found that the sorption processes followed the pseudo-second
      order rate kinetics with activation energy of 16.34 kJ mol(-1). The equilibration
      data fit best with the Langmuir isotherm the maximum copper sorption capacity of
      which is 119.43 mgg(-1). The mean free energy of copper sorption process
      calculated from Dubinin-Radushkevich model and the Polanyi potential concept was
      found to be in the range of 10.91-11.95 kJ mol(-1) showing that the main
      mechanism governing the sorption process is ion exchange. The negative values
      found for enthalpy change (-14.797 kJ mol(-1) over the range of 25-55 degrees C)
      and free energy change (-19.361 kJ mol(-1) for 25 degrees C) indicate that the
      sorption process is exothermic and spontaneous in nature.

PMID- 17499921
TI  - Study pharmacologic of the GABAergic and glutamatergic drugs on seizures and
      status epilepticus induced by pilocarpine in adult Wistar rats.
AB  - This work was designed to study the influence of drugs during seizures and status
      epilepticus (SE) induced by pilocarpine and mortality in adult rats. Glutamate
      (10 and 20 mg/kg), N-methyl-d-aspartate (NMDA, 5 and 10 mg/kg), ketamine (1.5 and
      2.0 mg/kg), gabapentin (200 and 250 mg/kg), phenobarbital (50 and 100 mg/kg) and
      vigabatrin (250 and 500 mg/kg) were administered intraperitoneally, 30 min prior
      to pilocarpine (400 mg/kg, i.p.). The animals were observed (24 h) to determine:
      number of peripheral cholinergic signs, tremors, stereotyped movements, seizures,
      SE, latency to first seizure and number of deaths after pilocarpine treatment.
      NMDA and glutamate had pro-convulsive effects in both doses tested. Smaller and
      higher doses of these drugs no protected and increased pilocarpine-induced
      seizures and/or mortality. Gabapentin, vigabatrin, phenobarbital and ketamine
      protected against seizures and increased the latency to first seizure. Thus,
      these results suggest that caution should be taken in the selection of
      pharmacotherapy and dosages for patients with seizures and SE because of the
      possibility of facility the convulsive process toxicity, SE and the mortality of
      adult animals in this seizures model that is similar temporal lobo epilepsy in
      humans.

PMID- 17499922
TI  - Protective effects of Abeta-derived tripeptide, Abeta(32-34), on Abeta(1-42)
      induced phosphatidylinositol 4-kinase inhibition and neurotoxicity.
AB  - We previously reported that the neurotoxicity of pathophysiological
      concentrations of amyloid beta proteins (Abetas, 0.1-10nM) as assessed by the
      inhibition of type II phosphatidylinositol 4-kinase (PI4KII) activity and the
      enhancement of glutamate toxicity was blocked by a short fragment of Abeta,
      Abeta(31-35). Such protective effects of shorter fragments derived from Abeta(31
      35) were examined in this study to reach the shortest effective peptide, using
      recombinant human PI4KII and primary cultured rat hippocampal neurons. Among the
      peptides tested (Abeta(31-34), Abeta(31-33), Abeta(31-32), Abeta(32-35), Abeta(33
      35), Abeta(34-35), Abeta(32-34), Abeta(33-34) and Abeta(32-33)), Abeta(31-34),
      Abeta(32-35) and Abeta(32-34) blocked both the Abeta(1-42)-induced inhibition of
      PI4KII activity and enhancement of glutamate toxicity on cell viability. The
      shortest peptide among them, Abeta(32-34), showed a dose-dependent protective
      effect with 50% effective concentration near 1nM, while Abeta(34-32), with a
      reverse amino acid sequence for Abeta(32-34), showed no protective effects. Thus,
      a tripeptide, Abeta(32-34) i.e. Ile-Gly-Leu, may be available as a lead compound
      for designing effective Abeta antagonists.

PMID- 17499923
TI  - Predicting maternal and behavioral measures of infant pain: the relative
      contribution of maternal factors.
AB  - The Sociocommunication Model of Infant Pain [Craig KD, Pillai Riddell R. Social
      influences, culture and ethnicity. In: Finley GA, McGrath PJ, editors. Pediatric
      pain: biological and social context, Seattle: IASP Press; 2003.] theorizes that
      maternal variables influence the pained infant and that the pained infant
      reciprocally influences maternal responses to the infant. The current analysis
      examines the relative predictive utility of maternal behavioral and psychosocial
      variables for both maternal judgments of her infant's pain and behavioral
      measures of infant pain, after infant factors have been controlled. A convenience
      sample of 75 mother-infant dyads was videotaped during a routine immunization in
      a pediatrician's office. Mothers were interviewed on the telephone, within two
      weeks, to complete a series of questionnaires. Infants were between the ages of 5
      and 20 months. Infant pain was measured directly after the immunization using
      subjective maternal judgments. In addition, both maternal soothing behaviors and
      infant pain behaviors post-immunization were measured using objective coding
      systems. During the telephone interview, mothers were asked to recall infant pain
      levels for the day after the immunization and were also assessed for level of
      acculturative stress, perceived social support, general relationship style,
      feelings towards her infant and endorsed psychopathology. Regression analyses
      suggested that the role of maternal behavioral and psychosocial variables was
      highly dependent on the infant pain measure being predicted. These results imply
      that given the dependence of infants on their primary caregivers, quite often
      mothers, it is important to understand the dynamic influence of infants' behavior
      on maternal judgments of infants' pain and maternal psychosocial variables on
      infants' expression of pain.

PMID- 17499924
TI  - Onset and progression of dystonia in complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) may lead to movement disorders (MDs) in
      some patients. Reliable information on the nature, chronology and clinical
      determinants of MDs in CRPS patients is lacking but could provide better insight
      in to the underlying pathophysiological mechanism. We retrospectively evaluated
      the clinical and temporal characteristics of MDs in patients with CRPS. Cox's
      proportional hazards model was used to evaluate factors influencing the onset of
      MDs. One-hundred and eighty-five patients suffered CRPS in one or more
      extremities. MDs occurred in 121 patients, with dystonia (91%) being the most
      prevalent. Sixty-two percent of these patients displayed dystonia in multiple
      extremities. Patients with dystonia were on average 11 years younger and more
      often had CRPS in multiple extremities. The interval between the onset of CRPS
      and dystonia in the first affected extremity varied from less than 1 week in 26%
      of the patients to more than 1 year in 27%. The hazard of developing dystonia in
      subsequent extremities increased with the number of extremities affected by
      dystonia. We conclude that dystonia in CRPS shows highly variable onset latency
      and is associated with younger age at onset and increased risk of developing
      dystonia in other extremities. The delayed onset and progression of dystonia in
      CRPS may indicate the involvement of a different underlying mechanism, possibly
      associated with maladaptive neuroplasticity.

PMID- 17499925
TI  - Activation of the 5-HT1B/D receptor reduces hindlimb neurogenic inflammation
      caused by sensory nerve stimulation and capsaicin.
AB  - Activation of the 5-HT(1B/D) receptor inhibits cerebrovascular neurogenic
      inflammation (NI). The aim of this study was to determine if the 5-HT(1B/D)
      receptor agonist sumatriptan can also inhibit NI in other regions of the body. NI
      was assessed by measuring plasma extravasation (PE) and changes in blood flow in
      the rat hindpaw. Sumatriptan was administered locally (20 microl, 50 or 100 nM,
      s.c.) into the dorso-medial region of one hindpaw. The other paw was pre-treated
      with vehicle (20 microl of 0.9% saline) and served as a control. NI was induced
      after treatment with sumatriptan/vehicle by injecting capsaicin (15 microl, 1%,
      s.c.) into each paw or by electrically stimulating the saphenous nerve (4 Hz,
      30s). Sumatriptan administered locally or systemically (300 microg/kg, i.v.)
      significantly reduced saphenous nerve and capsaicin-induced PE and vasodilation.
      The systemic and local inhibitory actions of sumatriptan are mediated by the 5
      HT(1B/D) receptor as pre-treatment with the 5-HT(1B/D) antagonist GR127935 (GR;
      15 microl, 1 microM, s.c. or 0.2 micromol/kg, i.v.) completely blocked the
      inhibitory effect of sumatriptan on capsaicin-induced vasodilation and reduced
      the inhibitory effect of sumatriptan on capsaicin and electrically induced-PE.
      Neither PE induced by local injection of substance P (SP) (20 pmol, 20 microl,
      s.c.) nor vasodilation induced by local CGRP injection was affected by pre
      treatment with sumatriptan. These findings indicate that both local and systemic
      activation of the 5-HT(1B/D) receptor by sumatriptan reduce NI induced by nerve
      stimulation or capsaicin presumably by inhibiting neuropeptide release. 5
      HT(1B/D) receptor agonists may be useful for the treatment of non-trigeminal pain
      conditions involving NI.

PMID- 17499926
TI  - Redesign of the scanning electron microscope for parallel energy spectral
      acquisition.
AB  - This paper presents a scanning electron microscope (SEM) design that is
      compatible with parallel electron energy spectrum acquisition. The SEM should in
      principle be capable of capturing the energy spectrum of all scattered electrons
      simultaneously, from low energy secondary electrons to elastic backscattered
      electrons. Preliminary simulation results predict that the beam separator
      spectrometer will have a relatively high transmission-energy resolution
      performance, comparable or better than the cylindrical mirror analyzer (CMA),
      while at the same time being able to capture the entire energy range of scattered
      electrons.

PMID- 17499928
TI  - The efficacy of aloe vera used for burn wound healing: a systematic review.
AB  - Aloe vera has been traditionally used for burn healing but clinical evidence
      remains unclear. We conducted a systematic review to determine the efficacy of
      topical aloe vera for the treatment of burn wounds. We electronically searched
      relevant studies in MEDLINE, CINAHL, Cochrane Library, HealthSTAR, DARE, South
      East Asia Database, Chinese Databases, and several Thai local Databases (1918
      June 2004). Only controlled clinical trials for burn healing were included. There
      were no restrictions on any language of publication. Two reviewers independently
      extracted data on study characteristics, patient characteristics, intervention,
      and outcome measure. Four studies with a total of 371 patients were included in
      this review. Based on a meta-analysis using duration of wound healing as an
      outcome measure, the summary weighted mean difference in healing time of the aloe
      vera group was 8.79 days shorter than those in the control group (P=0.006). Due
      to the differences of products and outcome measures, there is paucity to draw a
      specific conclusion regarding the effect of aloe vera for burn wound healing.
      However, cumulative evidence tends to support that aloe vera might be an
      effective interventions used in burn wound healing for first to second degree
      burns. Further, well-designed trials with sufficient details of the contents of
      aloe vera products should be carried out to determine the effectiveness of aloe
      vera.

PMID- 17499929
TI  - Where to start? Attempting to meet the psychological needs of burned patients.
AB  - The National Burn Care Review Committee [National Burn Care Review Committee.
      National Burns Care Review. Standards and Strategy for Burn Care; 2001] recommend
      routine psychosocial screening for all burned in-patients, as well as access to
      different levels of psychological input. This paper aims to report on: (1) a
      system which integrates routine clinical practice, psychological screening and a
      system of data collection to identify level of need; (2) an audit of the range of
      levels of psychological input required to meet this need. All consecutive
      admissions (n=72) to a regional burns unit were screened within a week of
      admission using the Hospital Anxiety and Depression Scale (HADS), the Impact of
      Event Scale (IES) and a screening tool developed in the unit. Clinical input was
      provided as required and recorded. Thirty-five percent reported a previous mental
      health problem. Forty percent fell into 'borderline' or 'caseness' on the HADS.
      Fifteen percent met a level of clinical 'caseness' on both the intrusions and
      avoidance subscales of the IES. Sixty-three percent required some level of
      psychological input during their in-patient stay. Given the high level of need
      identified and the range of levels of psychological intervention identified, a
      system of routine screening and a tiered model of psychological care is proposed
      to best utilise psychological resources.

PMID- 17499930
TI  - Nociceptin/orphanin FQ decreases serotonin efflux in the rat brain but in
      contrast to a kappa-opioid has no antagonistic effect on mu-opioid-induced
      increases in serotonin efflux.
AB  - Similar to kappa-opioids, nociceptin/orphanin FQ (OFQ) exerts anti-mu-opioid
      actions. This may involve interactions within the circuitry controlling 5-HT
      neurons in the dorsal raphe nucleus (DRN) that project to the nucleus accumbens
      (NAcc). To test this hypothesis, we compared the effects of OFQ and kappa-opioids
      on 5-HT efflux in the CNS of freely behaving rats. First, OFQ (30-300 microM)
      infused into the DRN for 120 min dose-dependently decreased 5-HT efflux in the
      DRN. The opioid receptor-like 1 (ORL-1) antagonist [Nphe(1)]nociceptin(1-13)NH(2)
      blocked this effect. Using dual-probe microdialysis we observed that OFQ (300
      microM) infused into the DRN for 120 min produced parallel decreases in 5-HT
      efflux in the DRN and NAcc, suggesting that ORL-1 receptors in the DRN inhibit
      serotonergic neurons projecting to the NAcc. Also, 5-HT efflux in the NAcc was
      dose-dependently decreased during OFQ (30-300 microM) infusion into the NAcc.
      This suggests that OFQ can reduce 5-HT efflux in the NAcc both by inhibiting
      serotonergic neurons in the DRN and by stimulating ORL-1 receptors in the NAcc.
      Similar to OFQ, the kappa-opioids U-50,488 (300 microM) and dynorphin A(1-13)
      (300 microM) infused into the DRN for 120 min decreased 5-HT efflux in the DRN.
      This effect was blocked only by the kappa-opioid receptor antagonist nor-BNI.
      Lastly, we compared the ability of OFQ and U-50,488 to block mu-opioid-induced
      increases in 5-HT. The kappa-opioid U-50,488 (1000 microM) attenuated the
      increase in 5-HT induced by the mu-opioid agonist endomorphin-1 (300 microM) in
      the DRN. In contrast, OFQ (300-1000 microM) did not alter mu-opioid-induced
      increases in 5-HT efflux. In summary, kappa-opioids and OFQ both decreased 5-HT
      efflux in the CNS. However, in contrast to kappa-opioids, which reversed mu
      opioid-induced increases in 5-HT efflux, the anti-mu-opioid effects of OFQ
      apparently do not involve changes in 5-HT transmission under our experimental
      conditions.

PMID- 17499931
TI  - Beta-amyloid pathology in the entorhinal cortex of rats induces memory deficits:
      implications for Alzheimer's disease.
AB  - Alzheimer's disease is characterized by the presence of senile plaques in the
      brain, composed mainly of aggregated amyloid-beta peptide (Abeta), which plays a
      central role in the pathogenesis of Alzheimer's disease and is a potential target
      for therapeutic intervention. Amyloid plaques occur in an increasing number of
      brain structures during the progression of the disease, with a heavy load in
      regions of the temporal cortex in the early phases. Here, we investigated the
      cognitive deficits specifically associated with amyloid pathology in the
      entorhinal cortex. The amyloid peptide Abeta(1-42) was injected bilaterally into
      the entorhinal cortex of rats and behavioral performance was assessed between 10
      and 17 days after injection. We found that parameters of motor behavior in an
      open-field as well as spatial working memory tested in an alternation task were
      normal. In contrast, compared with naive rats or control rats injected with
      saline, rats injected with Abeta(1-42) showed impaired recognition memory in an
      object recognition task and delayed acquisition in a spatial reference memory
      task in a water-maze, despite improved performance with training in this task and
      normal spatial memory in a probe test given 24 h after training. This profile of
      behavioral deficits after injection of Abeta(1-42) into the entorhinal cortex was
      similar to that observed in another group of rats injected with the excitotoxic
      drug, N-methyl-d-aspartate. Immunohistochemical analysis after behavioral testing
      revealed that Abeta(1-42) injection induced a reactive astroglial response and
      plaque-like deposits in the entorhinal cortex. These results show that
      experimentally-induced amyloid pathology in the entorhinal cortex induces
      selective cognitive deficits, resembling those observed in early phases of
      Alzheimer's disease. Therefore, injection of protofibrillar-fibrillar Abeta(1-42)
      into the entorhinal cortex constitutes a promising animal model for investigating
      selective aspects of Alzheimer's disease and for screening drug candidates
      designed against Abeta pathology.

PMID- 17499932
TI  - On the participation of hippocampal PKC in acquisition, consolidation and
      reconsolidation of spatial memory.
AB  - Memory consolidation involves a sequence of temporally defined and highly
      regulated changes in the activation state of several signaling pathways that
      leads to the lasting storage of an initially labile trace. Despite appearances,
      consolidation does not make memories permanent. It is now known that upon
      retrieval well-consolidated memories can become again vulnerable to the action of
      amnesic agents and in order to persist must undergo a protein synthesis-dependent
      process named reconsolidation. Experiments with genetically modified animals
      suggest that some PKC isoforms are important for spatial memory and earlier
      studies indicate that several PKC substrates are activated following spatial
      learning. Nevertheless, none of the reports published so far analyzed
      pharmacologically the role played by PKC during spatial memory processing. Using
      the conventional PKC and PKCmu inhibitor 12-(2-cyanoethyl)-6,7,12,13-tetrahydro
      13-methyl-5-oxo-5H-indolo[2,3-a]pyrrollo[3,4-c]carbazole (Go6976) we found that
      the activity of these kinases is required in the CA1 region of the rat dorsal
      hippocampus for acquisition and consolidation of spatial memory in the Morris
      water maze learning task. Our results also show that when infused into dorsal CA1
      after non-reinforced retrieval, Go6976 produces a long-lasting amnesia that is
      independent of the strength of the memory trace, suggesting that post-retrieval
      activation of hippocampal PKC is essential for persistence of spatial memory.

PMID- 17499933
TI  - Task specific influences of Parkinson's disease on the striato-thalamo-cortical
      and cerebello-thalamo-cortical motor circuitries.
AB  - The motor deficits in Parkinson's disease (PD) have been primarily associated
      with internally guided (IG), but not externally guided (EG), tasks. This study
      investigated the functional mechanisms underlying this phenomenon using
      genetically-matched twins. Functional magnetic resonance images were obtained
      from a monozygotic twin pair discordant for clinical PD. Single-photon emission
      computed tomography neuroimaging using [(123)I](-)-2-beta-carboxymethoxy-3-beta
      (4-iodophenyl)tropane confirmed their disease-discordant status by demonstrating
      a severe loss of transporter binding in the PD-twin, whereas the non-PD-twin was
      normal. Six runs of functional magnetic resonance imaging (fMRI) data were
      acquired from each twin performing EG and IG right-hand finger sequential tasks.
      The percentage of voxels activated in each of several regions of interest (ROI)
      was calculated. Multiple analysis of variance was used to compare each twin's
      activity in ROIs constituting the striato-thalamo-cortical motor circuits [basal
      ganglia (BG)-cortical circuitry, but including the globus pallidus/putamen,
      thalamus, supplementary motor area, and primary motor cortex] and cerebello
      thalamo-cortical circuits (cerebellar-cortical circuitry, including the
      cerebellum, thalamus, somatosensory cortex, and lateral premotor cortex). During
      the EG task, there were no significant differences between the twins in bilateral
      BG-cortical pathways, either basally or after levodopa, whereas the PD-twin had
      relatively increased activity in the cerebellar-cortical pathways basally that
      was normalized by levodopa. During the IG task, the PD-twin had less activation
      than the non-PD-twin in ROIs of the bilateral BG-cortical and cerebellar-cortical
      pathways. Levodopa normalized the hypoactivation in the contralateral BG-cortical
      pathway, but "over-corrected" the activation in the ipsilateral BG-cortical and
      bilateral cerebellar-cortical pathways. In this first fMRI study of twins
      discordant for PD, the data support the hypothesis that BG-cortical and
      cerebellar-cortical pathways are task-specifically influenced by PD. The levodopa
      induced "over-activation" of BG-cortical and cerebellar-cortical pathways, and
      its relevance to both compensatory changes in PD and the long-term effects of
      levodopa in PD, merit further exploration.

PMID- 17499935
TI  - Transtheoretical principles and processes for quitting smoking: a 24-month
      comparison of a representative sample of quitters, relapsers, and non-quitters.
AB  - This longitudinal study compared 14 principles and processes of change applied by
      successful quitters, relapsers and non-quitters over 24 months in a
      representative sample of 4144 smokers in intervention and control groups. The
      successful quitters showed a decrease in the use of experiential processes
      (cognitive, affective and effective) and an increase in behavioral processes
      (e.g., counter-conditioning and stimulus control). The non-quitters showed little
      change in their use of almost all of the processes. The relapsers' use of the
      processes tended to initially parallel the successful quitters, but over time,
      their use ended up between the quitters and the non-quitters. In general, the
      relapsers ended up working harder but not smarter than the successful quitters.
      The pattern of use of change processes in the treatment and control groups were
      remarkably similar, suggesting common pathways to change.

PMID- 17499934
TI  - Beta-amyloid disrupted synaptic vesicle endocytosis in cultured hippocampal
      neurons.
AB  - Neuronal death leading to gross brain atrophy is commonly seen in Alzheimer's
      disease (AD) patients. Yet, it is becoming increasingly apparent that the
      pathogenesis of AD involves early and more discrete synaptic changes in affected
      brain areas. However, the molecular mechanisms that underlie such synaptic
      dysfunction remain largely unknown. Recently, we have identified dynamin 1, a
      protein that plays a critical role in synaptic vesicle endocytosis, and hence, in
      the signaling properties of the synapse, as a potential molecular determinant of
      such dysfunction in AD. In the present study, we analyzed beta-amyloid (Abeta)
      induced changes in synaptic vesicle recycling in rat cultured hippocampal
      neurons. Our results showed that Abeta, the main component of senile plaques,
      caused ultrastructural changes indicative of impaired synaptic vesicle
      endocytosis in cultured hippocampal neurons that have been stimulated by
      depolarization with high potassium. In addition, Abeta led to the accumulation of
      amphiphysin in membrane fractions from stimulated hippocampal neurons. Moreover,
      experiments using FM1-43 showed reduced dye uptake in stimulated hippocampal
      neurons treated with Abeta when compared with untreated stimulated controls.
      Similar results were obtained using a dynamin 1 inhibitory peptide suggesting
      that dynamin 1 depletion caused deficiency in synaptic vesicle recycling not only
      in Drosophila but also in mammalian neurons. Collectively, these results showed
      that Abeta caused a disruption of synaptic vesicle endocytosis in cultured
      hippocampal neurons. Furthermore, we provided evidence suggesting that Abeta
      induced dynamin 1 depletion might play an important role in this process.

PMID- 17499936
TI  - The 'Hittite plague', an epidemic of tularemia and the first record of biological
      warfare.
AB  - A long-lasting epidemic that plagued the Eastern Mediterranean in the 14th
      century BC was traced back to a focus in Canaan along the Arwad-Euphrates trading
      route. The symptoms, mode of infection, and geographical area, identified the
      agent as Francisella tularensis, which is also credited for outbreaks in Canaan
      around 1715 BC and 1075 BC. At first, the 14th century epidemic contaminated an
      area stretching from Cyprus to Iraq, and from Israel to Syria, sparing Egypt and
      Anatolia due to quarantine and political boundaries, respectively. Subsequently,
      wars spread the disease to central Anatolia, from where it was deliberately
      brought to Western Anatolia, in what constitutes the first known record of
      biological warfare. Finally, Aegean soldiers fighting in western Anatolia
      returned home to their islands, further spreading the epidemic.

PMID- 17499937
TI  - Botulinum toxin, Quo Vadis?
AB  - Botulinum toxin (BTX), derived from the exotoxin of Clostridium botulinum,
      cleaves Soluble N-ethylmaleimide-sensitive factor-Attachment protein REceptor
      (SNARE) proteins, causing chemodenervation of cholinergic neurons. BTX also
      inhibits exocytosis of vesicles containing norepinephrine, glutamate, substance P
      and calcitonin gene-related peptide (CGRP) and inhibits expression of the
      vanilloid receptor. Clinical applications of BTX, which include the treatment of
      overactive skeletal and smooth muscles, hypersecretory and painful disorders,
      have increased exponentially since it was first used clinically to treat
      strabismus more than two decades ago. In this editorial, we discuss reports of
      new therapeutic indications of BTX, and propose new areas for research.

PMID- 17499938
TI  - Dietary phytochemicals as quorum sensing inhibitors.
AB  - Quorum sensing (QS) is a cell density dependent expression of species in bacteria
      mediated by hormone like compounds called autoinducers (AI). Several processes
      responsible for successful establishment of bacterial infection are mediated by
      QS. Inhibition of QS is therefore being considered as a new target for
      antimicrobial chemotherapy. Dietary phytochemicals are secondary metabolites in
      plants known to have several health benefits including antimicrobial activity.
      However, their ability to inhibit QS has never been studied. Our objective was to
      investigate the effect of sub-lethal concentrations (SLC) of bioactive dietary
      phytochemical extracts from common dietary fruit, herb and spice extracts on
      modulating QS mediated by AI in model bioassay test systems. QS inhibition was
      measured in violacein pigment producing Chromobacterium violaceum O26 (CVO26) and
      CV 31532 system, mediated by AI known as acylated homeserine lactone (AHL). We
      also investigated the effect of the sub-lethal concentrations of the extracts on
      swarming motility of pathogens Escherichia coli (EC)O157:H7 and Pseudomonas
      aeruginosa (PA-01). Our results indicate that all extracts significantly
      inhibited quorum sensing. The mechanism of inhibition appeared to be combination
      of interfering with AHL activity and modulating the synthesis of AHL's. Our
      results also indicated that various phytochemical extracts which inhibited QS
      also inhibited swarming of pathogenic bacteria, known to be modulated by QS. The
      observation that phytochemicals from foods can inhibit QS related processes opens
      up an exciting new strategy for antimicrobial chemotherapy and lead to the
      discovery of new category of antibiotics which can overcome the issues related to
      antimicrobial resistance.

PMID- 17499939
TI  - Antimicrobial activity of four species of Berberidaceae.
AB  - Ethanolic extracts of the stems and leaves of Nandina domestica, Mahonia
      fortunei, Mahonia bealei and Berberis thunbergii were tested for their
      antibacterial and antifungal activity. Most of the extracts have been proved to
      be active against Gram(+) bacteria.

PMID- 17499940
TI  - Composition and alpha-amylase inhibitory effect of essential oils from Cedrus
      libani.
AB  - The inhibitory activity of alpha-amylase and the phytochemical composition of
      Cedrus libani essential oils obtained from wood, leaves and cones were
      investigated. The C. libani woods oil exhibit an IC(50) value of 0.14 mg/ml,
      whereas the leaves and cones oils were devoid of any significant activity.

PMID- 17499941
TI  - Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans
      and mice.
AB  - Indoleamine 2,3-dioxygenase (INDO) and tryptophan 2,3-dioxygenase (TDO) each
      catalyze the first step in the kynurenine pathway of tryptophan metabolism. We
      describe the discovery of another enzyme with this activity, indoleamine 2,3
      dioxygenase-like protein (INDOL1), which is closely related to INDO and is
      expressed in mice and humans. The corresponding genes have a similar genomic
      structure and are situated adjacent to each other on human and mouse chromosome
      8. They are likely to have arisen by gene duplication before the origin of the
      tetrapods. The expression of INDOL1 is highest in the mouse kidney, followed by
      epididymis, and liver. Expression of mouse INDOL1 was further localized to the
      tubular cells in the kidney and the spermatozoa. INDOL1 was assigned its name
      because of its structural similarity to INDO. We demonstrate that INDOL1
      catalyses the conversion of tryptophan to kynurenine therefore a more appropriate
      nomenclature for the enzymes might be INDO-1 and INDO-2, or the more commonly
      used abbreviations, IDO-1 and IDO-2. Although the two proteins have similar
      enzymatic activities, their different expression patterns within tissues and
      during malaria infection, suggests a distinct role for each protein. This
      identification of INDOL1 may help to explain the regulation of the diversity of
      physiological and patho-physiological processes in which the kynurenine pathway
      is involved.

PMID- 17499942
TI  - Counting of single prion particles bound to a capture-antibody surface (surface
      FIDA).
AB  - Hitherto accredited prion tests use the PK resistance of PrP(Sc), the pathogenic
      isoform of the prion protein, as a marker for the disease. Because of variations
      in the amount of disease-related aggregated PrP, which is not PK-resistant, these
      prion tests offer only limited sensitivity. Therefore, a prion detection method
      that does not rely on PK digestion would allow for the detection of both PK
      resistant as well as PK-sensitive PrP(Sc). Furthermore, single particle counting
      is more sensitive than methods measuring an integrated signal. Our new test
      system is based on dual-colour fluorescence correlation spectroscopy (FCS). This
      method quantifies the number of protein aggregates that have been simultaneously
      labelled with two different antibodies using dual-colour fluorescence intensity
      distribution analysis (2D-FIDA). This only counts PrP aggregates, and not PrP
      monomers. To increase the sensitivity, PrP(Sc) was concentrated in a two
      dimensional space by immobilizing it so that the antibodies could be captured on
      the surface of the slide (surface-FIDA). When the surface was systematically
      scanned, even single prion particles were detected. Using this new technique, the
      sensitivity to identify samples from scrapie-infected hamster as well as BSE
      infected cattle can be dramatically increased in comparison with identification
      using FIDA in solution.

PMID- 17499943
TI  - Phylogenetic characterization of Newcastle disease viruses isolated in Taiwan
      during 2003-2006.
AB  - Isolates of Newcastle disease virus (NDV) from chicken cases were obtained from
      various locations in Taiwan during 2003-2006 and were genotypically analyzed by
      using reverse transcription polymerase chain reaction (RT-PCR) with primers
      specific to the viral fusion (F) protein gene (534 bp). Part of the amplified F
      protein DNA product (nucleotide sequence 47-418) and the deduced amino acid
      sequences were compared phylogenetically with those from strains previously
      reported in Taiwan and other geographic regions. Our results showed that all
      Taiwanese isolates (n=20) collected during 2003-2006, according to the
      phylogenetic tree, belong to the genotype VIId. In addition, all the six
      Taiwanese isolates obtained in 2003, carry the motif (112)R-R-Q-K-R(116) and have
      the amino acid L(23) replaced by F(23) (assigned as Group 1). On the other hand,
      12 out of the 14 Taiwanese isolates obtained during 2004-2006 possess the motif
      (112)R-R-K-K-R(116) and have the amino acid G(74), instead of E(74) (assigned as
      Group 2). To our best knowledge, this is the first reported VIId isolates that
      possess the sequences of G(74)/(112)R-R-K-K-R(116) within the F0 protein. Since a
      high mortality, severe clinical signs, typical postmortem lesions, and a high
      intra-cerebral pathogenicity index (ICPI) were observed in the NDV-infected
      chickens, these isolates acquired between 2003 and 2006 are considered as the
      velogenic type. The Group 2 viruses have become dominant and responsible for the
      majority of Taiwanese outbreaks during recent years. Based on our phylogenetic
      analysis, it can be postulated that these isolates were evolved from previously
      reported local strains, and the Group 2 family emerged the latest in the genotype
      VIId. The information is fundamental to improving the efficiency of controlling
      strategies and vaccine development for NDV.

PMID- 17499944
TI  - Maternal smoking during pregnancy and behaviour problems in a birth cohort of 2
      year-old Pacific children in New Zealand.
AB  - AIM: The present study investigated associations between maternal smoking during
      pregnancy and child behaviour problems in a cohort of Pacific Islands two-year
      old children in New Zealand. STUDY DESIGN: Data were gathered as part of the
      Pacific Islands Families (PIF) Study. Mothers of a cohort of 1398 Pacific infants
      born in South Auckland, New Zealand were interviewed when their children were six
      weeks, 12 and 24 months of age. Within the context of a wider interview, data
      regarding cigarette smoking during pregnancy was obtained from 1038 biological
      mothers at the six-week interview and reports of child behaviour using the Child
      Behaviour Checklist were gathered when the children were 24 months old. RESULTS:
      The prevalence rates of clinically relevant cases were higher in children of
      smokers compared to non-smokers for internalising (22.6% versus 15.2%),
      externalising (9.6% versus 5.7%) and total problem scores (20% versus 12.4%).
      Following adjustment for potential confounding factors, smoking was associated
      with a moderately increased prevalence of total behaviour problems (OR=1.75, 95%
      CI=(1.12, 2.74); p=0.015). For internalising scores, the effects of smoking
      appeared to be raised for children of non-partnered mothers (OR=3.35, 95%
      CI=(1.29, 8.67); p=0.013). For externalising scores, smoking appeared to have a
      greater detrimental effect on girls (OR=2.37, 95% CI=(1.12, 5.04); p=0.024).
      CONCLUSIONS: Findings indicate there are significant effects of prenatal tobacco
      exposure on problem behaviour among young children. Smoking is a modifiable
      factor worthy of increased early preventive efforts.

PMID- 17499945
TI  - Study of apoptosis-related markers in ram spermatozoa.
AB  - Certain features of capacitated or frozen-thawed spermatozoa have been considered
      to be an apoptosis-like phenomenon, and, it has been suggested that the presence
      of apoptotic sperm in seminal doses could be one of the reasons for poor
      fertility. The objective of this study was to determine whether
      phosphatidylserine (PS) translocation, caspase activity and DNA fragmentation,
      which are considered to be apoptotic markers in somatic cells, occur in ram
      sperm. Fresh ejaculates and sperm samples in different physiological state (cold
      shocked, in vitro capacitated and acrosome-reacted (AR)) were compared.
      Simultaneous staining with 6-carboxifluorescein diacetate (6-CFDA) and Annexin V
      Cy3.18 (AnnV) revealed four different sperm subpopulations in ejaculates. The
      main subpopulation was composed of viable cells without PS exposure (CFDA+/AnnV
      ). A total of 40.8% of sperm showed inverted PS, with two levels of alteration:
      CFDA+/AnnV+ in midpiece ("type I AnnV+"), and in acrosome and midpiece ("type II
      AnnV+"). The fewest subpopulation contained non-viable cells showing Annexin
      labelling in the entire cell (CFDA-/AnnV+). Labeling of caspases-3 and -7 by
      immunocytochemistry revealing different sperm subtypes depending on their
      localization in apical, equatorial, post-acrosomal regions and tail. The results
      obtained by western-blot showed, for the first time to our knowledge, that
      caspase-like proteins are present in fresh ram semen as both inactive and active
      forms. The proportion of sperm with fragmented DNA [terminal transferase-mediated
      dUDP nick end-labeling (TUNEL)-positive] were found rarely (2.7+/-0.5%) in all
      fresh ejaculates involved in this study. The analysis of total activity of both
      caspases by a fluorometric method showed a decrease in vitro capacitated and
      acrosome-reacted samples as well as in cryoinjured samples. However, the
      percentage of TUNEL-positive sperm demonstrating DNA fragmentation was
      significantly increased after in vitro induced capacitation and acrosome
      reaction, as well as after cold-shock although this augment was not significant.
      PS exposure is not totally dependent on caspases in ram spermatozoa as the
      addition of a caspase inhibitor prevented the increase in PS inversion due to
      incubation in capacitating conditions but not to the ionophore-induced acrosome
      reaction or cold-shock.

PMID- 17499946
TI  - Temporal relationships among LH, estradiol, and follicle vascularization
      preceding the first compared with later ovulations during the year in mares.
AB  - Diameter of the preovulatory follicle, plasma concentrations of LH and estradiol,
      and vascularization of the follicle wall, based on color-Doppler signals, were
      characterized in 40 pony mares for 6 days preceding ovulation (Days -6 to -1;
      preovulatory period). Comparisons between the preovulatory periods preceding the
      first compared with a later ovulation during the year were used to study the
      relationships between LH and estradiol and between vascularization and estradiol.
      Diameter of the preovulatory follicle was greater (P<0.02) and concentration of
      LH was less (P<0.02) during the first preovulatory period, whereas concentration
      of estradiol was not different between the first and second preovulatory periods.
      Vascularized area (cm(2)) of the follicle wall increased at a reduced rate during
      the first preovulatory period, as indicated by an interaction (P<0.03) between
      day and group. Vascularized area was similar between the preovulatory groups on
      Day -6, and a reduced rate of increase resulted in a lesser (P<0.001) area on Day
      -1 before the first ovulation (1.4+/-0.1cm(2)) than before a later ovulation
      (2.2+/-0.2 cm(2)). Results demonstrated that follicle vascularization and the LH
      surge were attenuated preceding the first ovulation of the year with no
      indication that estradiol was involved in the differences between the first and
      later ovulations.

PMID- 17499947
TI  - Measurement of surface color as an expedient QC method for the detection of
      deviations in tablet hardness.
AB  - The objective of this study was to investigate whether a correlation exists
      between the surface color of tablets and their tensile strength. Theophylline
      powder blends with and without red dye were directly compressed into 600mg
      tablets. Applied compression pressure ranged from 9.3 to 271.2MPa. Colorimetric
      parameters: lightness (L), chromaticity (a, b), chroma (Cab), hue (hab) and color
      intensity (CI), were measured and recorded for both sides of each tablet using
      ColorQuest XE colorimeter in reflectance specular included mode. The tensile
      strength of the tablets was measured using a TA.XTPlus Texture Analyzer. A linear
      correlation was observed between the chroma (Cab) parameter and the tensile
      strength for each formulation of the tablets. For white tablets, the linearity
      was observed between Cab values ranging from 2.6 to 3.76 and tensile strength
      values ranging from 2.96 to 6.86MPa. For red tablets, the linearity was observed
      between a chroma range from 21.76 to 30.75 and tensile strength from 2.51 to
      6.52MPa. A similar correlation was observed between the CI of red tablets and
      tensile strength. It was concluded that chroma could be used as suitable QC
      parameters to detect deviations in tablet hardness during bulk manufacturing.

PMID- 17499948
TI  - UEA I-bearing nanoparticles for brain delivery following intranasal
      administration.
AB  - Surface engineering of nanoparticles with lectins opened a novel pathway to
      improve the brain uptake of agents loaded by biodegradable PEG-PLA nanoparticles
      following intranasal administration. Ulex europeus agglutinin I (UEA I),
      specifically binding to l-fucose, which is largely located in the olfactory
      epithelium, was selected as a promising targeting ligand and conjugated onto the
      PEG-PLA nanoparticles surface with an optimized protocol relying on maleimide
      mediated covalent binding technique. The in vivo results in rats suggested that
      UEA I modification at the nanoparticles surface facilitated the absorption of a
      fluorescent marker--6-coumarin associated with the nanoparticles into the brain
      following intranasal administration with significant increase in the area under
      the concentration-time curve (about 1.7 times) in different brain tissues
      compared with that of coumarin incorporated in the unmodified ones. UEA I
      conjugation also elevated the brain-targeting efficiency of nanoparticles.
      Inhibition experiment of specific sugar suggested that the interactions between
      the nasal mucosa and the lectinised nanoparticles were due to the immobilization
      of carbohydrate-binding pockets on the surface of the nanoparticles. Distribution
      profiles of UEA I-modified nanoparticles indicated their higher affinity to the
      olfactory mucosa than to the respiratory one. Therefore, the UEA I-modified
      nanoparticles might serve as potential carriers for brain drug delivery,
      especially for mental therapeutics with multiple biological effects.

PMID- 17499949
TI  - Development and optimization of a novel oral controlled delivery system for
      tamsulosin hydrochloride using response surface methodology.
AB  - The purpose of this study was to develop and optimize oral controlled-release
      formulations for tamsulosin hydrochloride using a combination of two cellulose
      ester derivatives, hydroxypropyl methylcellulose (HPMC) and hydroxypropyl
      methylcellulose phthalate (HPMCP), with Surelease as a coating material. A three
      factor, three-level Box-Behnken design was used to prepare systematic model
      formulations, which were composed of three formulation variables, the content of
      HPMC (X(1)) and HPMCP (X(2)) and the coating level (X(3)), as independent
      variables. The response surface methodology (RSM) and multiple response
      optimization utilizing the polynomial equation were used to search for the
      optimal coating formulation with a specific release rate at different time
      intervals. The drug release percentages at 2, 3 and 5h were the target responses
      and were restricted to 15-30% (Y(1)), 50-65% (Y(2)) and 80-95% (Y(3)),
      respectively. The optimal coating formulation was achieved with 10% HPMC and 20%
      HPMCP at a coating level of 25%, and the observed responses coincided well with
      the predicted values from the RSM optimization technique. The drug release from
      pellets coated with the optimized formulation showed a controlled-release pattern
      (zero-order), in comparison with a commercial product (Harunal capsule). In
      conclusion, a novel, oral, controlled-release delivery system for tamsulosin
      hydrochloride was successfully developed by incorporating HPMC and HPMCP as
      coating additives into Surelease aqueous ethylcellulose dispersion.

PMID- 17499950
TI  - Finnish guidelines for workplace drug testing.
AB  - The Finnish guidelines for workplace drug testing outlined here represent what is
      considered the best practice for workplace drug testing to be followed in
      Finland. The guidelines are based on the act on the protection of privacy in
      working life (759/2004), the occupational health care act (1383/2001) and the
      decree on workplace drug testing (218/2005). They start by defining situations in
      which workplace testing is allowed and continue up to the point where the
      certificate is submitted to the employer. The role of the occupational health
      care system is crucial in the procedure. The guidelines include the best practice
      procedures to be followed by laboratories providing workplace drug testing
      services. The laboratory recommendations are based on general principles
      established internationally. In the Finnish guidelines, accreditation is an
      absolute prerequisite for a laboratory functioning as a workplace drug testing
      laboratory. The laboratory section of the guidelines includes specimen
      collection, laboratory organisation, analysis procedure, quality assurance and
      quality control measures. These largely conform to the European laboratory
      guidelines for legally defensible workplace drug testing published by the
      European workplace drug testing society (EWDTS), but there are differences. In
      addition to using urine as a specimen, the Finnish guidelines also encompass
      blood.

PMID- 17499951
TI  - Quantitative analysis of emphysema in 3D using MDCT: influence of different
      reconstruction algorithms.
AB  - PURPOSE: The aim of the study was to compare the influence of different
      reconstruction algorithms on quantitative emphysema analysis in patients with
      severe emphysema. MATERIAL AND METHODS: Twenty-five patients suffering from
      severe emphysema were included in the study. All patients underwent inspiratory
      MDCT (Aquilion-16, slice thickness 1/0.8mm). The raw data were reconstructed
      using six different algorithms: bone kernel with beam hardening correction (BHC),
      soft tissue kernel with BHC; standard soft tissue kernel, smooth soft tissue
      kernel (internal reference standard), standard lung kernel, and high-convolution
      kernel. The only difference between image data sets was the algorithm employed to
      reconstruct the raw data, no additional radiation was required. CT data were
      analysed using self-written emphysema detection and quantification software
      providing lung volume, emphysema volume (EV), emphysema index (EI) and mean lung
      density (MLD). RESULTS: The use of kernels with BHC led to a significant decrease
      in MLD (5%) and EI (61-79%) in comparison with kernels without BHC. The absolute
      difference (from smooth soft tissue kernel) in MLD ranged from -0.6 to -6.1 HU
      and were significant different for all kernels. The EV showed absolute
      differences between -0.05 and -0.4 L and was significantly different for all
      kernels. The EI showed absolute differences between -0.8 and -5.1 and was
      significantly different for all kernels. CONCLUSION: The use of kernels with BHC
      led to a significant decrease in MLD and EI. The absolute differences between
      different kernels without BHC were small but they were larger than the known
      interscan variation in patients. Thus, for follow-up examinations the same
      reconstruction algorithm has to be used and use of BHC has to be avoided.

PMID- 17499952
TI  - A multi-center, comparative, phase 3 study to determine the efficacy of
      gadofosveset-enhanced magnetic resonance angiography for evaluation of renal
      artery disease.
AB  - PURPOSE: To determine prospectively the safety and efficacy of the blood-pool
      contrast agent gadofosveset trisodium in renal artery magnetic resonance
      angiography (MRA). MATERIALS AND METHODS: Gadofosveset (0.03 mmol/kg) was
      administered to adult patients with known or suspected renal arterial disease in
      a multi-center phase 3 single dose study. The drug binds reversibly to albumin,
      prolonging the blood residence time, and allowing collection of images in the
      first-pass and steady-state phases. The combination of these images was compared
      to non-contrast MRA, using catheter X-ray angiography (XRA) as the standard of
      reference (SOR). All MRA images were collected at 1.5 T in one imaging session
      for direct comparison, and XRA within 30 days. Sensitivity, specificity, and
      accuracy for diagnosing significant disease (stenosis > or =50%) were calculated
      for MRA using three independent blinded readers. Patient safety was monitored for
      72-96 h. RESULTS: A total of 145 patients at 18 centers were enrolled and
      received gadofosveset; the 127 with complete efficacy data entered the primary
      efficacy analysis. Gadofosveset-enhanced MRA led to significant improvement
      (p<0.01) in sensitivity (+25%, +26%, +42%), specificity (+23%, +25%, +29%), and
      accuracy (+23%, +28%, +29%) over non-enhanced MRA for the three readers. The rate
      of uninterpretable examinations decreased from 30% to less than 2%. There were no
      serious adverse events, and the most common adverse events were nausea, pruritus,
      and headache (8% each). No significant trends in clinical chemistry parameters,
      nor significant changes in serum creatinine, were found following administration
      of gadofosveset. CONCLUSION: In patients with known or suspected renal arterial
      disease, multi-phase gadofosveset-enhanced MRA significantly improves
      sensitivity, specificity, and accuracy versus non-enhanced MRA. Gadofosveset was
      safe and well tolerated in this patient population.

PMID- 17499953
TI  - A transmit/receive volume strip array and its mode mixing theory in MRI.
AB  - MRI is increasingly moving towards higher magnetic field, prompting the need for
      multi-port transmit/receive RF coil arrays to overcome high-frequency limitations
      such as penetration depth and dielectric resonance effects. In this work, an
      arbitrary n-element transmit/receive volume strip array (VSA) and an associated
      mixing mode theory are described to understand the behavior of a multiple-port
      cyclic symmetrical VSA in both the physical port space and the complementary mode
      space; the relations between the two spaces are explicitly formulated. The
      advantage of mode-space analysis is that an arbitrary n x n impedance matrix
      which describes any VSA in port space can be diagonalized to a diagonal n x n
      matrix; thus an analytical solution of Kirchhoff's laws for the VSA becomes
      manageable when n is large. Based on such an analytical solution, we can (a)
      generate excitation profile of any desired mixed mode during transmission by
      manipulating external power sources without the need of physically tuning VSA to
      the mixed mode; (b) identify the sensitivity profiles of the complementary mode
      distributions during reception, which were unknown in quadrature and decoupled
      coils. Many predictions are rigidly verified by extensive test measurements from
      network analyzer and by MR imaging experiments.

PMID- 17499954
TI  - A feasibility study of a web-based performance improvement system for substance
      abuse treatment providers.
AB  - We report here on the feasibility of implementing a semiautomated performance
      improvement system-Patient Feedback (PF)-that enables real-time monitoring of
      patient ratings of therapeutic alliance, treatment satisfaction, and drug/alcohol
      use in outpatient substance abuse treatment clinics. The study was conducted in
      six clinics within the National Institute on Drug Abuse Clinical Trials Network.
      It involved a total of 39 clinicians and 6 clinic supervisors. Throughout the
      course of the study (consisting of five phases: training period [4 weeks],
      baseline [4 weeks], intervention [12 weeks], postintervention assessment [4
      weeks], sustainability [1 year]), there was an overall collection rate of 75.5%
      of the clinic patient census. In general, the clinicians in these clinics had
      very positive treatment satisfaction and alliance ratings throughout the study.
      However, one clinic had worse drug use scores at baseline than other
      participating clinics and showed a decrease in self-reported drug use at
      postintervention. Although the implementation of the PF system proved to be
      feasible in actual clinical settings, further modifications of the PF system are
      needed to enhance any potential clinical usefulness.

PMID- 17499955
TI  - Does following research-derived practice guidelines improve opiate-dependent
      patients' outcomes under everyday practice conditions? Results of the Multisite
      Opiate Substitution Treatment study.
AB  - The Multisite Opiate Substitution Treatment study evaluated whether adhering to
      clinical-trial-derived practice guidelines improves treatment outcomes of
      unselected opiate-dependent patients seen in everyday practice. Clinics that were
      relatively concordant (n = 4) or nonconcordant (n = 4) with guidelines concerning
      medication dose levels and psychosocial service provision were identified. Staff
      interviewed 256 patients at intake and 6-month follow-up regarding past month
      heroin use, criminal activities, and mental health. To represent real-world
      practice conditions, clinics provided care in accordance with their usual
      approach, and no patient exclusion criteria were employed. Patients in each type
      of clinic were similar at baseline, but by follow-up, heroin use and mental
      health outcomes were significantly better in guideline-concordant clinics than in
      guideline-discordant clinics. Notably, 60.6% of patients in concordant clinics
      had urinalysis-confirmed heroin abstinence versus only 40.0% in nonconcordant
      clinics. Following research-derived practice guidelines seems to increase opiate
      substitution treatment effectiveness for opiate-dependent patients in the real
      world.

PMID- 17499956
TI  - The accessibility of substance abuse treatment facilities in the United States
      for persons with disabilities.
AB  - This study assessed the accessibility of a nationally representative sample of
      substance abuse treatment facilities in the United States for persons with
      disabilities (PWDs). A stratified random sample of 159 substance abuse treatment
      facilities in 40 states completed a survey regarding physical accessibility and
      the provision of services that could enhance the ability to serve individuals
      with disabilities. Most responding facilities self-reported a variety of barriers
      to physical accessibility, as well as the lack of services and physical
      accommodations for persons with sensory limitations. Such widespread
      inaccessibility may be a factor that promotes the low representation of PWDs in
      the treatment population.

PMID- 17499957
TI  - Reliability of college student self-reported drinking behavior.
AB  - College students represent a unique population among substance users, with
      developmental needs and motivational factors different from those of other adults
      with substance abuse problems. As most college-based treatment programs focus on
      harm reduction, the reliability of self-reported substance use is critical to
      assessing treatment needs and outcomes. This study examined the reliability of
      students' self-reported alcohol consumption for the month prior to entering a
      treatment program at two points in time. It was hypothesized that: (a) students
      required to attend a drug and alcohol educational program would underreport their
      history of use when asked about it at intake (Time 1), relative to their self
      report of use for the same historical timeframe after attending the program (Time
      2); and (b) students would describe these discrepancies as a function of feeling
      more or less concerned about the impact of their disclosure. Findings supported
      both hypotheses. Implications for an evaluation of student drinking behaviors are
      discussed.

PMID- 17499958
TI  - Ethnic differences in utilization of drug treatment services and outcomes among
      Proposition 36 offenders in California.
AB  - This study examined whether ethnic differences exist in access to care, receipt
      of services, and associated outcomes of 1,057 offenders participating in
      California's Proposition 36. Data are based on intake and 3-month follow-up
      interviews conducted as part of a multisite prospective treatment outcome study.
      Logistic regressions were conducted to examine ethnicity and other predictors of
      treatment placement and services intensity. Across ethnic groups, services
      intensity in several domains was inadequately matched to need, and few services
      besides substance abuse treatment were provided. Blacks and Hispanics received
      alcohol and employment services that were not commensurate with their greater
      need. Although Blacks were more likely to be placed in residential programs,
      their employment status worsened from intake to follow-up. There were few other
      ethnic differences in outcomes. Assessing and eliminating ethnic-associated
      differences in health service delivery, even as moderate as our findings
      revealed, may improve program processes and outcomes.

PMID- 17499959
TI  - Availability of addiction medications in private health plans.
AB  - Health plans have implemented cost sharing and administrative controls to
      constrain escalating prescription expenditures. These policies may impact
      physicians' prescribing and patients' use of these medications. Important
      clinical advances in the pharmacological treatment of addiction highlight the
      need to examine how pharmacy benefits consider medications for substance
      dependence. The extent of restrictions influencing the availability of these
      medications to consumers is unknown. We use nationally representative survey data
      to examine the extent and stringency of private health plans' management of
      naltrexone and disulfiram for alcohol dependence, and buprenorphine for opiate
      dependence. Thirty-one percent of insurance products excluded buprenorphine from
      formularies, whereas 55% placed it on the highest cost-sharing tier. Generic
      naltrexone is the only substance dependence medication that is both rarely
      excluded from formularies and usually placed on a lower cost-sharing tier. These
      findings demonstrate that pharmacy benefits have an impact on access to
      medications for substance abuse.

PMID- 17499960
TI  - Injection drug users' perceptions of drug treatment services and attitudes toward
      substitution therapy: a qualitative study in three Russian cities.
AB  - This study explored injection drug users' (IDUs) perceptions of drug abuse
      treatment and treatment providers in three Russian cities as well as their
      attitudes toward opiate substitution therapy, which is currently not available in
      Russia. Data were collected from 121 qualitative interviews with IDUs conducted
      in 2003-2004. Negative perceptions of available treatments were related to poor
      treatment outcomes, judgmental service providers, lack of psychologic services,
      and short lengths of stay in treatment. Positive perceptions were associated with
      receiving psychosocial care and nonjudgmental attitudes from providers. Most
      participants had heard about opiate substitution therapy, and some had treated
      themselves using methadone from the black market. Although respondents had doubts
      that opiate substitution therapy could work effectively in Russia, most agreed
      that this type of treatment would help IDUs function better in the society.

PMID- 17499961
TI  - Process improvement needs in substance abuse treatment: admissions walk-through
      results.
AB  - Researchers have questioned whether the addiction treatment infrastructure will
      be able to deliver high-quality care to the large numbers of people in need. In
      this context, the Robert Wood Johnson Foundation and the Center for Substance
      Abuse Treatment created a nationwide network to improve access and retention in
      treatment. Applicant agencies described results of an admission process walk
      through. This qualitative study used narrative text from 327 applications to the
      Robert Wood Johnson Foundation, focusing on admissions-related problems. We
      developed and applied a coding scheme and then extracted themes from code-derived
      text. Primary themes described problems reported during treatment admissions:
      poor staff engagement with clients; burdensome procedures and processes;
      difficulties with addressing the clients' complex lives and needs; and
      infrastructure problems. Subthemes elucidated specific process-related problems.
      Although the findings from our analyses are descriptive and exploratory, they
      suggest the value of walk-through exercises for program assessment and program
      level factors that may affect treatment access and retention.

PMID- 17499962
TI  - Global transcriptional response of porcine mesenteric lymph nodes to Salmonella
      enterica serovar Typhimurium.
AB  - To elucidate the host transcriptional response to Salmonella enterica serovar
      Typhimurium, Affymetrix porcine GeneChip analysis of pig mesenteric lymph nodes
      was used to identify 848 genes showing differential expression across different
      times after inoculation or when compared to non-inoculated controls. Annotation
      analyses showed that a high proportion of these differentially expressed (DE)
      genes are involved in immune and inflammatory responses. T helper 1,
      innate/inflammatory, and antigen-processing pathways were induced at 24 h post
      inoculation (hpi) and/or 48 hpi, while apoptosis and antigen
      presentation/dendritic cell function pathways were downregulated at 8 hpi.
      Cluster analyses revealed that most DE genes annotated as NFkappaB targets were
      grouped into a specific induced subcluster, while many translation-related DE
      genes were found in a repressed subcluster. Quantitative polymerase chain
      reaction analyses confirmed the Affymetrix results, revealing transcriptional
      induction of NFkappaB target genes at 24 hpi and suppression of the NFkappaB
      pathway from 24 to 48 hpi. We propose that such NFkappaB suppression in antigen
      presenting cells may be the mechanism by which S. Typhimurium eludes a strong
      inflammatory response to establish a carrier status in pigs.

PMID- 17499963
TI  - Surgical pathology of infected aortic aneurysm and its clinical correlation.
AB  - Pathology of infected aortic aneurysm and its clinical correlation have rarely
      been reported. Between 1995 and 2005, 48 patients with infected aortic aneurysm
      underwent in situ graft replacement. Twenty-five patients had a suprarenal and 23
      patients had an infrarenal infection. The most common responsible pathogen was
      nontyphoid Salmonella in 32 patients (67%). During operation, gross pus was
      present in 26 patients (54%). On pathological examination, aortic atherosclerosis
      was present in all cases, acute suppurative inflammation was present in 31
      patients (65%), and bacterial clumps were present in five patients (10%).
      Positive culture of the aneurysm wall was present in 14 patients (29%). There
      were 10 patients with prosthetic graft infection (21%) and 12 patients with
      aneurysm-related death (25%). Although statistically insignificant, local
      purulent infection with positive culture of the aneurysm wall, gross pus during
      operation, or acute suppurative inflammation on pathology tended to be associated
      with high risk of prosthetic graft infection and aneurysm-related death. In
      conclusion, infected aortic aneurysm occurred in patients with aortic
      atherosclerosis. On pathology, acute suppurative inflammation was present in the
      majority of cases but bacterial clumps were not commonly present. Local purulent
      infection tended to be associated with high risk of prosthetic graft infection
      and aneurysm-related death.

PMID- 17499964
TI  - Percutaneous therapy to maintain dialysis access successfully prolongs functional
      duration after primary failure.
AB  - The role of endovascular therapy for thrombosed dialysis access has grown despite
      the paucity of data on its viability. The purpose of this study was to
      characterize the outcomes of a universal endovascular dialysis declot policy at a
      tertiary medical center. A database of patients undergoing endovascular treatment
      of thrombosed dialysis access between 1997 and 2003 was maintained. A two
      puncture, combined percutaneous mechanical and pharmacologic thrombectomy
      technique was used. Data were collected on the success rate, complication rate,
      long-term patency, and presence and location of stenosis. Fistulograms were
      reviewed in all cases to assess lesion characteristics and pre- and postprocedure
      results. Results were standardized to current Society of International Radiology
      and Society for Vascular Surgery criteria. Failure was considered as either an
      anatomic defect requiring therapy or loss of functionality of the fistula. Life
      table analyses were performed to assess time-dependent outcomes. Cox's
      proportional hazard analyses were performed to identify factors associated with
      outcomes. Values are the mean +/- standard error of the mean. There were 114
      patients (50% male; average age 58 years, range 21-78) who presented with 174
      thrombosed grafts. Therapy was performed for 237 thrombotic events (median 2,
      range 1-5 thrombotic events per hemodialysis access). After successful declot,
      anastomotic venous stenoses were encountered in 72% and central venous stenoses
      in 18% of cases; no cause was found in 10%. All stenoses were treated with
      balloon angioplasty. The technical failure rate was 4.6%. The 30-day all-cause
      mortality rate was 1.7%, and major morbidity rate was 2.4%. There were 413
      interventions (236 percutaneous transluminal angioplasty and/or 183 declot)
      performed to maintain patency, which amounted to 2.3 interventions per patient.
      Average primary functional dialysis life span was 6.7 months up to the primary
      thrombotic event. Aggressive endoluminal therapy added a further average of 12
      months of functionality (defined as continued dialysis access). A universal
      policy of endovascular therapy for occluded dialysis access results in
      reestablishment of function in the majority of patients and will triple
      functional longevity. Furthermore, while this approach remains procedure
      intensive, it carries low morbidity and mortality and preserves future sites of
      access.

PMID- 17499965
TI  - Convenient and accurate landing technique for the frozen elephant trunk.
AB  - Accurate distal landing is essential to avoid paraplegia while performing the
      frozen elephant trunk technique (FETT). A 72-year-old man who had a hippocampus
      shape aneurysm in the descending aorta was successfully treated by the FETT with
      a certain and sophisticated method to position the Stent graft precisely using a
      16-F nephrostomy balloon catheter. No cerebrospinal complications were observed
      postoperatively, and computed tomography did not reveal any endleakage.

PMID- 17499966
TI  - Cutaneous hyperpigmentation after endovenous laser therapy: a case report and
      literature review.
AB  - Endovenous laser therapy (EVLT) for the treatment of varicose veins has been
      shown to be effective and relatively safe. Reported complications are few and
      transient. Whereas it is not uncommon to have cutaneous hyperpigmentation
      following treatment modalities such as sclerotherapy, only a few reports of
      transient hyperpigmentation following EVLT have been mentioned in the literature.
      We report a case of persistent hyperpigmentation following successful varicose
      vein treatment by EVLT.

PMID- 17499967
TI  - A prospective analysis of critical limb ischemia: factors leading to major
      primary amputation versus revascularization.
AB  - In our aging population, primary major amputations (AMP, below-knee or above
      knee) continue to be performed despite advances in revascularization. We
      hypothesized that not only patient comorbidities but also the system of health
      care delivery affected the treatment of patients with critical limb ischemia
      (CLI). A prospective analysis of patients presenting with CLI was undertaken to
      determine whether patient-specific factors or healthcare delivery factors (system
      related) influenced treatment with primary AMP versus lower extremity
      revascularization (LER). The patient-specific factors age, gender,
      race/ethnicity, presence of coronary artery disease, cerebrovascular disease,
      tobacco use, diabetes mellitus (DM), dialysis dependence (end-stage renal
      disease, ESRD), hypertension, hyperlipidemia, stage of CLI (rest pain, minor or
      major tissue loss), history of revascularization, and functional status (living
      situation and ambulatory status) were recorded. The system-related factors time
      from onset of CLI to vascular surgery evaluation and type of insurance (managed
      care/other insurance) were also noted. The influence of patient-specific and
      system-related factors on the primary treatment modality (AMP versus LER) was
      determined with univariate and multivariate analyses. A total of 224 patients
      presented with CLI between March 1, 2001, and March 1, 2005. Patients were
      treated with primary major AMP in 97 cases (43%) and revascularization in 127
      cases (57%). On univariate analysis, nonwhite race/ethnicity, DM, ESRD, major
      tissue loss, dependent living situation, and nonambulatory status were all
      significant predictors of AMP versus LER (all P < 0.01). On multivariate
      analysis, major tissue loss, ESRD, DM, and nonambulatory status remained
      independent predictors of AMP versus LER (all P < 0.05). The system-related
      factors of time to vascular surgery evaluation (mean 8.6 weeks, 7.1 vs. 9.3 weeks
      AMP versus LER, P = 0.60) and type of insurance (managed care, 17% vs. 24% AMP
      vs. LER, P = 0.15) had no influence on treatment. Fifty-four percent of all
      primary major AMPs were performed due to extensive gangrene or infection present
      at initial vascular evaluation which precluded limb salvage. Major tissue loss,
      ESRD, DM, and nonambulatory status are all independent predictors of treatment
      with primary AMP as opposed to revascularization. Treatment of CLI is determined
      by patient-specific factors and does not appear to be adversely influenced by
      system-related factors. Efforts toward improving limb salvage may be best
      directed at aggressive treatment of medical comorbidities to prevent the late
      complications of CLI. Earlier recognition of tissue loss and referral to the
      vascular specialist may lead to improved limb salvage.

PMID- 17499968
TI  - Duplex ultrasonography rarely changes management decisions in chronic lower
      extremity ischemia.
AB  - The purpose of this study was to determine the proportion of patients presenting
      with lower extremity pain whose treatment plan was altered by duplex
      ultrasonography. This prospective study evaluated all patients referred for lower
      extremity pain who had undergone a lower extremity arterial duplex scan. All
      patients underwent a history and physical examination by the same vascular
      surgeon. After the completion of the history and physical examination, the
      surgeon established a preliminary treatment plan. Subsequently, he reviewed the
      lower extremity duplex results and established a final treatment plan based on
      the history, physical examination, and duplex results. Treatment was labeled as
      either (1) conservative, (2) aggressive, or (3) the patient was considered to
      have no peripheral vascular disease. The proportion of patients whose primary
      treatment plan was altered by the addition of duplex ultrasonography was
      determined. Of 103 patients who entered the study, 7% had no peripheral vascular
      disease based on the history, physical examination, and duplex scan. Based on the
      history and physical examination alone, 48.5% were to be treated conservatively
      and 44.7% aggressively. After reviewing duplex results, the treatment plan was
      changed in only 5.9% of patients. There was no difference in treatment plan after
      the addition of the duplex results (p = 0.1025). Duplex ultrasonography remains a
      valuable tool in the evaluation of patients with lower extremity peripheral
      vascular disease; however, in most patients, the decision to treat conservatively
      or aggressively can be made without duplex scanning. All patients referred to the
      vascular clinic for lower extremity evaluation do not require a duplex scan.

PMID- 17499969
TI  - Computer vision guided virtual craniofacial reconstruction.
AB  - The problem of virtual craniofacial reconstruction from a sequence of computed
      tomography (CT) images is addressed and is modeled as a rigid surface
      registration problem. Two different classes of surface matching algorithms,
      namely the data aligned rigidity constrained exhaustive search (DARCES) algorithm
      and the iterative closest point (ICP) algorithm are first used in isolation.
      Since the human bone can be reasonably approximated as a rigid body, 3D rigid
      surface registration techniques such as the DARCES and ICP algorithms are deemed
      to be well suited for the purpose of aligning the fractured bone fragments. A
      synergistic combination of these two algorithms, termed as the hybrid DARCES-ICP
      algorithm, is proposed. The hybrid algorithm is shown to result in a more
      accurate mandibular reconstruction when compared to the individual algorithms
      used in isolation. The proposed scheme for virtual reconstructive surgery would
      prove to be of tremendous benefit to the operating surgeons as it would allow
      them to pre-visualize the reconstructed mandible (i.e., the end-product of their
      work), before performing the actual surgical procedure. Experimental results on
      both phantom and real (human) patient datasets are presented.

PMID- 17499970
TI  - Omega-3 polyunsaturated fatty acids affect lipopolysaccharide-induced maturation
      of dendritic cells through mitogen-activated protein kinases p38.
AB  - OBJECTIVE: The omega-3 polyunsaturated fatty acids (PUFAs) play a key role as
      immune response modulators and suppressors of immunologic functions, such as
      lymphocyte proliferation, cytokine production, and cell surface molecular
      expression in T lymphocytes, monocytes, and natural killer cells. However, little
      is known about the effect of omega-3 PUFAs on dendritic cells (DCs). We studied
      the effect of omega-3 PUFAs on DCs and the related intracellular signal
      transduction pathway. METHODS: Dendritic cells were generated from human
      peripheral blood monocytes in the presence of granulocyte-macrophage colony
      stimulating factors and interleukin (IL)-4 and treated with eicosapentaenoic acid
      (EPA), docosahexanoic acid (DHA), and stearic acid for 24 h. Lipopolysaccharide
      (LPS) was used for maturation of the DCs. The expressions of CD40, CD80, CD86,
      and human leukocyte antigen-DR (HLA-DR) were analyzed by flow cytometry;
      production of IL-12 and tumor necrosis factor-alpha were detected by reverse
      transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay.
      The proliferative ability of allogeneic T cells stimulated by DCs was evaluated
      by tritiated thymidine ((3)H-TdR). Western blot analysis of p38 mitogen-activated
      protein kinase was conducted. RESULTS: The omega-3 PUFAs reduced expression
      levels of costimulatory molecules CD80 and CD86 and major histocompatibility
      complex HLA-DR. IL-12 and tumor necrosis factor-alpha levels decreased
      significantly in the EPA and DHA groups. EPA and DHA also significantly reduced
      the proliferative ability of allogeneic T cells stimulated by DCs. The omega-3
      PUFAs significantly inhibited LPS-induced p38 phosphorylation. CONCLUSION: The
      omega-3 PUFAs may inhibit LPS-induced DC maturation and upregulate cytokine
      production. Impaired p38 mitogen-activated protein kinase activity is a potential
      critical intracellular signaling transduction mechanism.

PMID- 17499971
TI  - Assessment of vitamin A nutritional status in newborn preterm infants.
AB  - OBJECTIVE: This study assessed the vitamin A nutritional status of preterm
      infants determined by the vitamin A relative dose-response test (RDR) compared
      with serum levels of vitamin A, retinol-binding protein (RBP), transthyretin
      (TTR), and retinol relations with carrier proteins. METHODS: Serum levels of
      retinol, RBP, and TTR and retinol/RBP, retinol/TTR, and RBP/TTR molar ratios were
      determined in 120 infants at 7 d and in 92 at 28 d. For the determination of the
      performance of the tests, the RDR was considered the reference method. The
      sensitivity and specificity for all possible cutoff values were determined by
      constructing receiver operator characteristic curves. The areas under the curves
      were used to estimate the overall accuracy of the tests. The best cutoff values
      to be used for the calculation of sensitivity and specificity were determined
      with 95% confidence intervals. RESULTS: RDR indicated vitamin A deficiency in 60%
      of the infants at 7 d and in 51.1% at 28 d. In the receiver operator
      characteristic curves, the best area under the curve was 0.710 obtained for serum
      retinol at 28 d of postnatal age and considered moderately accurate. The least
      inadequate cutoff level was set at 25 mg/dL, but no value was considered adequate
      due to low sensitivity and/or low specificity. CONCLUSION: Compared with RDR, the
      determination of serum levels of retinol, RBP, and TTR and their molar ratios are
      not adequate to assess nutritional vitamin A status in preterm infants.

PMID- 17499972
TI  - Probiotics and zinc in acute infectious gastroenteritis in children: are they
      effective?
AB  - OBJECTIVE: Several studies in recent decades have assessed the effects of
      different probiotics in acute gastroenteritis, showing that specific strains of
      Lactobacilli (mainly Lactobacillus casei GG) and Saccharomyces boulardii may
      exert some beneficial therapeutic actions, mainly when used in rotavirus
      gastroenteritis, at a high dose, and in the early phase. The mechanisms of action
      of probiotics are not completely elucidated but seem to involve a complex
      interaction among epithelial, molecular, metabolic, and immune responses. Data on
      the prevention of community-acquired, nosocomial, and travelers' diarrhea are
      currently conflicting. Because each micro-organism has different properties, an
      accurate selection of the strain, dose, and patient should be cautiously
      considered. METHODS AND RESULTS: Several reports from developing countries have
      demonstrated that supplements of zinc also provide significant reduction in stool
      output and duration, persistency, and severity of diarrhea. In view of the
      published data and of the different actions of zinc (such as improvement of the
      immune status, intestinal permeability, epithelial and enzymatic function, and
      electrolyte transport), the use of zinc as adjunctive therapy to oral rehydration
      solution has the potential to improve the management of diarrhea and decrease
      complications in children worldwide. In contrast to probiotics, which most trials
      in the developed world have used, there has been no trial with zinc performed in
      developed countries. CONCLUSION: Data on the effect of a combined administration
      of zinc and probiotics in acute gastroenteritis are urgently needed.

PMID- 17499973
TI  - Vitamin A deficiency does not influence longitudinal growth in mice.
AB  - OBJECTIVE: Growth hormone (GH) stimulates longitudinal growth, directly and
      indirectly, through the mediation of circulating and locally produced insulin
      like growth factor 1 (IGF-1). The exact role of individual vitamins in modulating
      GH secretion or action, and somatic growth in general, is still not completely
      understood. It has been suggested that vitamin A (VA) and its physiologic active
      metabolite retinoic acid influence longitudinal growth by promoting the
      differentiation of pituitary cells toward GH-secreting cells and by stimulating
      secretion of GH. Accordingly, epidemiologic studies have shown that short
      children have lower VA intake than do children with normal stature. METHODS: To
      determine whether VA deficiency causes impairment of GH secretion, we have
      investigated the effect of a severely VA-deficient diet on growth in mice. Ten
      male mice born from mothers fed with VA-deficient diet since conception were
      maintained on a VA-deficient diet until the end of week 8 of life. Ten male mice
      born from mothers fed with a VA-sufficient diet and receiving a normal diet after
      weaning served as the control group. At the end of the study, we measured
      animals' weight and length, body composition, tibia and femur lengths, liver
      retinol and retinyl esters storages, serum IGF-1, serum thyroxine, serum GH, and
      pituitary GH mRNA levels. RESULTS: Despite evidence of significant VA deficiency,
      we observed no effect on longitudinal growth or changes in pituitary GH mRNA,
      serum thyroxine, serum GH, or serum IGF-1 levels. CONCLUSION: VA deficiency does
      not negatively affect longitudinal growth and pituitary GH content and action in
      mice.

PMID- 17499974
TI  - Leptin and insulin homeostasis in epilepsy: relation to weight adverse
      conditions.
AB  - During managing patients with epilepsy, there is a great risk of weight changes,
      particularly weight gain with some antiepileptic medications. Weight gain is not
      only a cosmetic problem that leads to non-compliance to medications but also
      increases the risk for atherosclerosis and its related complications. The
      mechanisms underlying weight gain in epilepsy are multiple and controversial and
      have been attributed to the effect of epilepsy and more commonly the effect of
      antiepileptic medications on the central and peripheral mechanisms regulating
      weight homeostasis including the two main homeostatic hormones, leptin, a protein
      product of obesity gene secreted by adipocytes and insulin, a protein product of
      pancreatic beta-cells. Increased blood levels of leptin and insulin due to leptin
      and insulin resistance is observed in patients with epilepsy. Leptin forms an
      important link between weight gain, insulin resistance, epilepsy and
      atherosclerosis. The knowledge of the novel roles of leptin in patients with
      epilepsy will help identification of early markers for the related adverse weight
      changes, thus allowing proper characterization of suitable antiepileptic
      medication as initial step during management and follow up of patients.

PMID- 17499975
TI  - Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on
      human T lymphocyte function and gene expression.
AB  - Antidepressants have an antiproliferative effect in some cell lines. Depression
      may be associated with activation of some pro-inflammatory cytokines. Therefore,
      we evaluated the ex-vivo immunomodulatory effect of selective serotonin reuptake
      inhibitors (SSRIs) in T cells. We found that the SSRIs, paroxetine and sertraline
      decreased T-cell viability with IC50 around 10 microM. The inhibition obtained
      with exposure to the SSRIs was more pronounced than that achieved with
      dexamethasone. Moreover, these SSRIs inhibit the secretion of the TH1 factor
      tumor necrosis factor(TNF)alpha from the cells. On the molecular level, the SSRIs
      suppressed signal transducer and activator of transcription 3 (Stat3) and
      cyclooxygenase(Cox)2 protein expression. The inhibitory effects were accompanied
      by alterations in gene expression as assessed in the gene array. These findings
      reveal an immunomodulatory effect of the SSRIs paroxetine and sertraline in human
      T cells. The clinical implications of our findings merit further investigation.

PMID- 17499976
TI  - Hemin rescues adrenodoxin, heme a and cytochrome oxidase activity in frataxin
      deficient oligodendroglioma cells.
AB  - Mutations in the frataxin gene cause neurodegeneration and demyelination in
      Friedreich's ataxia. We showed earlier that frataxin deficiency causes primary
      iron-sulfur cluster defects, and later causes defects in heme and cytochrome c
      hemoprotein levels. Iron-sulfur (Fe/S) clusters are required in two enzymes of
      heme biosynthesis in humans i.e. in ferrochelatase and adrenodoxin. However,
      decreases in ferrochelatase activity have not been observed in frataxin-deficient
      HeLa cells or patient lymphoblasts. We knocked down frataxin in oligodendroglioma
      cells using siRNA, which produced significant defects in the activity of the Fe/S
      cluster enzymes adrenodoxin and aconitase, the adrenodoxin product heme a, and
      cytochrome oxidase, for which heme a serves as a prosthetic group. Exogenous
      hemin produced a significant rescue of adrenodoxin, aconitase, heme a levels and
      cytochrome oxidase activity. Thus hemin rescues iron-sulfur cluster defects that
      are the result of frataxin-deficiency, perhaps as a consequence of increasing the
      pool of bioavailable iron, and thus should be more fully tested for beneficial
      effects in Friedreich's ataxia models.

PMID- 17499977
TI  - Disruption of the mouse protein Ser/Thr phosphatase 2Cbeta gene leads to early
      pre-implantation lethality.
AB  - Protein phosphatase 2Cbeta (PP2Cbeta) is a member of a family of protein Ser/Thr
      phosphatases (PP2C) that is composed of at least twelve different gene products.
      Recent studies have revealed that PP2Cbeta mRNA accumulates in mature sperm,
      unfertilized metaphase II-arrested oocytes and zygotes, but that the mRNA level
      then decreases sharply between the early two-cell and eight-cell stages,
      remaining at low levels during the 16-cell to blastocyst stages of mice. These
      observations raised the possibility that PP2Cbeta plays a crucial role during
      gametogenesis, fertilization, and/or early stages of embryonic development. In
      this study, we employed a gene knockout technique in mice to test this
      possibility. We found that PP2Cbeta(Delta/wt) mice generate normal mature
      gametes. However, PP2Cbeta(Delta/Delta) embryos die between the two-cell and
      eight-cell stages. To our interest, PP2Cbeta(Delta/Delta) ES cells which had been
      generated by transfecting PP2Cbeta(3lox/3lox) ES cells with Cre-expressing
      plasmid were viable. In addition, knockdown of PP2Cbeta using siRNA did not
      affect the proliferation of wild-type ES cells. These observations suggest that
      relatively high PP2Cbeta expression is specifically required during the early
      stages of pre-implantation development. The possible mechanisms for the early pre
      implantation lethality of PP2Cbeta(Delta/Delta) mice are discussed.

PMID- 17499978
TI  - Secondary succession and its effects on soil moisture and nutrition in abandoned
      old-fields of hilly region of Loess Plateau, China.
AB  - Floristic composition, community structure and soil moisture and nutrient
      contents in abandoned fields of different ages were analyzed to clarify the
      regenerative aspects of succession as a tool for vegetation restoration. The
      results indicated that secondary succession in this region can be interpreted as
      an auto-succession: there are main changes in species-relative abundance and
      species turnover. Annual or biennial species (e.g. Artemisia scoparia), acted as
      pioneers and strongly dominated the early stages. Then, they underwent a
      progressive decline, while forbs (e.g. Artemisia sacrorum) and grasses (e.g.
      Xanthium sibiricum) had their peak abundance at intermediate stages. Dwarf shrubs
      (e.g. Lespedeza dahurica) and short rhizome grass (e.g. Bothriochloa ischaemum)
      appeared at mid-succession stage and gradually increased in abundance during
      succession, becoming dominant at late stages. The first axis of detrended
      correspondence canonical analysis arranged the sites according to their fallow
      time, indicating a successional sere. The second axis, associated with diverging
      pathways of regeneration, correlated with topographic factors and soil moisture
      and nutrition. Structural divergence between plots increased as succession went
      on, attained the highest at the mid-succession stage, decreased at the late
      stage. Soil moisture and available phosphorus content decreased steadily with
      field age after their abandonment, whereas pools of organic matter, total and
      available nitrogen, potassium and total phosphorus increased with field age. The
      pace and direction of recovery of native vegetation and natural soil properties
      in these abandoned fields resembled classic old-field succession, which is a form
      of secondary succession that often serves as a template for guiding restoration
      efforts. Interface between the abandoned field soil and plant system was crucial
      to the above process. Our current study supported the generally accepted
      hypothesis in the succession literature.

PMID- 17499979
TI  - A low-cost, disposable card for rapid polymerase chain reaction.
AB  - A low-cost, disposable card for rapid polymerase chain reaction (PCR) was
      developed in this work. Commercially available, adhesive-coated aluminum foils
      and polypropylene films were laminated with structured polycarbonate films to
      form microreactors in a card format. Ice valves [1] were employed to seal the
      reaction chambers during thermal cycling and a Peltier-based thermal cycler was
      configured for rapid thermal cycling and ice valve actuation. Numerical modeling
      was conducted to optimize the design of the PCR reactor and investigate the
      thermal gradient in the reaction chamber in the direction of sample thickness.
      The PCR reactor was experimentally characterized by using thin foil thermocouples
      and validated by a successful amplification of 10 copy of E. coli tuf gene in 27
      min.

PMID- 17499980
TI  - [New treatments of epilepsy in infancy].
AB  - Epilepsy is a repetition of seizures. It is frequent child pathology: 40% of all
      epileptic people have less than 15 years of age. Seizures appear on a developing
      brain. Treatment must avoid frequent and long lasting seizures but at the same
      time must spare cognitive development. New antiepileptic drugs seem to have more
      specialized indications, less side effects and thus represent a very interesting
      tool for neuropediatrician. Monotherapy has to be preferred as often as possible
      to assure good cognitive function.

PMID- 17499981
TI  - The role of the lymphatic system in subcutaneous absorption of macromolecules in
      the rat model.
AB  - The purpose of this study was to assess the contribution of lymphatics to the
      systemic bioavailability of macromolecules following SC administration in a rat
      model. The rat model included continuous lymph collection from the thoracic lymph
      duct and concurrent serial blood sampling from freely moving animals. A thoracic
      lymph duct-jugular vein shunt produced by an implanted connective cannula, and
      maintained during the recovery period, enabled superior rat survival and
      prevented lymphatic cannula occlusion. The SC absorption of three macromolecules
      (bovine insulin, bovine serum albumin, and recombinant human erythropoietin
      alpha) was assessed in comparison to the non-lymph cannulated control group. For
      all tested molecules, only minimal amounts (less than 3%) of the SC administered
      dose were detected in the collected lymph. In the rat model, following SC
      administration, the macromolecules were absorbed mainly through the blood
      capillaries with minimal contribution of the lymphatic system to systemic
      bioavailability. The relatively small elevation in the lymphatic concentration,
      which occurred in all molecules, may be attributed to the redistribution of the
      molecules from the blood to the interstitial fluid compartment. These findings
      are important since rodents are commonly used in preclinical evaluation of
      macromolecular drugs.

PMID- 17499982
TI  - Embryonic development of Python sebae - II: Craniofacial microscopic anatomy,
      cell proliferation and apoptosis.
AB  - This study explores the microscopic craniofacial morphogenesis of the oviparous
      African rock python (Python sebae) spanning the first two-thirds of the post
      oviposition period. At the time of laying, the python embryo consists of largely
      undifferentiated mesenchyme and epithelium with the exception of the cranial base
      and trabeculae cranii, which are undergoing chondrogenesis. The facial
      prominences are well defined and are at a late stage, close to the time when lip
      fusion begins. Later (11-12d), specializations in the epithelia begin to
      differentiate (vomeronasal and olfactory epithelia, teeth). Dental development in
      snakes is different from that of mammals in several aspects including an extended
      dental lamina with the capacity to form 4 sets of generational teeth. In
      addition, the ophidian olfactory system is very different from the mammalian.
      There is a large vomeronasal organ, a nasal cavity proper and an extraconchal
      space. All of these areas are lined with a greatly expanded olfactory epithelium.
      Intramembranous bone differentiation is taking place at stage 3 with some bones
      already ossifying whereas most are only represented as mesenchymal condensations.
      In addition to routine histological staining, PCNA immunohistochemistry reveals
      relatively higher levels of proliferation in the extending dental laminae, in
      osseous mesenchymal condensations and in the olfactory epithelia. Areas
      undergoing apoptosis were noted in the enamel organs of the teeth and osseous
      mesenchymal condensations. We propose that localized apoptosis helps to divide a
      single condensation into multiple ossification centres and this is a mechanism
      whereby novel morphology can be selected in response to evolutionary pressures.
      Several additional differences in head morphology between snakes and other
      amniotes were noted including a palatal groove separating the inner and outer row
      of teeth in the upper jaw, a tracheal opening within the tongue and a pharyngeal
      adhesion that closes off the pharynx from the oral cavity between stages 1 and 4.
      Our studies on these and other differences in the python will provide valuable
      insights into in developmental, molecular and evolutionary mechanisms of
      patterning.

PMID- 17499983
TI  - Bioabsorption of chromium from retan chrome liquor by cyanobacteria.
AB  - The bioaccumulation of chromium from retan chrome liquor by Spirulina fusiformis
      was investigated under laboratory as well as field conditions. At the optimal
      conditions, metal ion uptake increased with initial metal ion concentration up to
      300mg/l. The effect on various physico-chemical parameters like total solids
      (TS), total dissolved solids (TDS), total suspended solids (TSS), chlorides,
      sulphates, phenols, biochemical oxygen demand (BOD) and chemical oxygen demand
      (COD) and biochemical studies related to biomass, chlorophyll-a and protein were
      also carried out. The present study indicates that S. fusiformis is very
      effective in removal of chromium (93-99%) besides removing other toxicants from
      retan chrome liquor. The sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and FTIR studies indicate the interaction/complexation
      between Cr and alga. The mechanism involved in bioaccumulation of chromium is
      also discussed. The process when upgraded can be applied for detoxification of
      tannery effluents.

PMID- 17499984
TI  - Sensitivity analysis and literature review of parameters controlling local
      biodegradation processes in municipal solid waste landfills.
AB  - The local gas production rate in municipal landfills is influenced by a large
      number of processes, which have been modelled by a local mechanistic reaction
      model based on Monod kinetics. This type of model, however, requires over 40
      input parameters. The aim of this research was to review published values for
      these input parameters, and to analyse the sensitivity of the model to changes in
      each of them. Included were rate constants based on Monod kinetics, general rate
      controlling variables, and parameters that influence the local pH and temperature
      of the waste. Mathematical functions that describe the influence of water
      content, temperature, and pH on biodegradation rates were calibrated on the basis
      of literature data. The results of the sensitivity analysis suggest that the
      parameters with the largest impact on model output are the hydrolysis constant
      k(Hy), the kinetic constants mu(max,X(me,1), b(X)(me), Y (ac,X(me,1), K(i,ac,Hy),
      and Y(CO(2),X(me,2),) the water content, temperature, pH, initial concentration
      of X(me), the enthalpy of formation of the original organic matter, as well as
      the protein content and buffering capacity of the waste. These parameters,
      therefore, should be carefully selected when similar modelling studies are
      performed.

PMID- 17499985
TI  - Leaching of heavy metals from chromated copper arsenate (CCA) treated wood after
      disposal.
AB  - Wood treated by preservatives is commonly found in solid waste. Among the
      different types of preserved wood, chromated copper arsenate (CCA) treated wood
      recently has received much attention due to the scale of usage and its
      significant role in soil and water contamination. As the ash of CCA treated wood
      would be hazardous if the wood were to be incinerated, this is not a good
      alternative, and the best available disposal method is thus landfilling in the
      US, Canada and Australia. Leaching of the metals from preserved wood that is
      disposed in unlined landfills for construction debris pollutes the soil and water
      environments. Several factors affecting leaching of the metals from wood,
      including pH of the leachant, temperature, the duration of leaching and the type
      of leachant, were investigated. These factors affect each of the metals,
      chromium, copper and arsenic, differently. A comparison of these effects on each
      metal was performed. The results of the experiments showed that the pH of the
      leachants has a significant effect on the leaching process, and sulfuric acid (pH
      3) is the most effective leachant compared to nitric and acetic acid (pH 3-4-5).
      The amounts of leached chromium, copper and arsenic by sulfuric acid (pH 3)
      during 15 days were, respectively, 0.2, 0.14 and 0.15 mg more than leachates by
      nitric acid (pH 5) on the basis of 1g of wood (initial contents of 1.03 mg, 0.42
      g and 0.8 mg per g of wood). Most of the leaching occurs in the first 5 days, and
      the rate of leaching decreases significantly after 5 days. Increasing temperature
      increases the amount of leached metals, and arsenic is the least resistant metal
      to the leaching when the temperature increases. Increasing the temperature from
      15 degrees C to 35 degrees C during 15 days increases the amount of leached
      chromium, copper and arsenic by acetic acid at pH 5 by about 0.1, 0.4 and 1.2mg
      per g of wood, respectively.

PMID- 17499986
TI  - Life cycle based risk assessment of recycled materials in roadway construction.
AB  - This paper uses a life-cycle assessment (LCA) framework to characterize
      comparative environmental impacts from the use of virgin aggregate and recycled
      materials in roadway construction. To evaluate site-specific human toxicity
      potential (HTP) in a more robust manner, metals release data from a demonstration
      site were combined with an unsaturated contaminant transport model to predict
      long-term impacts to groundwater. The LCA determined that there were reduced
      energy and water consumption, air emissions, Pb, Hg and hazardous waste
      generation and non-cancer HTP when bottom ash was used in lieu of virgin crushed
      rock. Conversely, using bottom ash instead of virgin crushed rock increased the
      cancer HTP risk due to potential leachate generation by the bottom ash. At this
      scale of analysis, the trade-offs are clearly between the cancer HTP (higher for
      bottom ash) and all of the other impacts listed above (lower for bottom ash). The
      site-specific analysis predicted that the contaminants (Cd, Cr, Se and Ag for
      this study) transported from the bottom ash to the groundwater resulted in very
      low unsaturated zone contaminant concentrations over a 200 year period due to
      retardation in the vadose zone. The level of contaminants predicted to reach the
      groundwater after 200 years was significantly less than groundwater maximum
      contaminant levels (MCL) set by the US Environmental Protection Agency for
      drinking water. Results of the site-specific contaminant release estimates vary
      depending on numerous site and material specific factors. However, the
      combination of the LCA and the site specific analysis can provide an appropriate
      context for decision making. Trade-offs are inherent in making decisions about
      recycled versus virgin material use, and regulatory frameworks should recognize
      and explicitly acknowledge these trade-offs in decision processes.

PMID- 17499987
TI  - Congenital abnormalities and clinical features associated with Wilms' tumour: a
      comprehensive study from a centre serving a large population.
AB  - Altogether 156 children treated for Wilms' tumour (WT) between 1970 and 1998 were
      studied. Sixty-six children, selected only by their attendance at clinic, were
      carefully examined and the findings compared to those from a case note review of
      90 children. Congenital abnormalities were present in 45% of the examined cohort,
      in 19% of the case notes review group and in 30% overall. Novel findings included
      the association of WT with Marshall Smith syndrome, developmental delay in 3 of 4
      cases of WT (one bilateral) and 1 sibling from consanguineous Pakistani families
      and another sibling also had leukaemia. The possibility of rare DNA repair or
      cancer predisposing disorders among these 4 families requires further study.
      Careful examination and history taking of an unselected patient cohort revealed a
      higher than expected incidence of clinical abnormalities which may be overlooked
      if not specifically sought.

PMID- 17499988
TI  - Does endocrine therapy for the treatment and prevention of breast cancer affect
      memory and cognition?
AB  - Oestrogen receptors have been identified in several areas of the brain important
      in cognitive performance, including the prefrontal cortex (active during short
      term working memory), the hippocampus and related cortical areas (learning and
      storage of information) and the amygdala (involved in the modulation of memory
      consolidation). There is much debate as to whether or not a reduction in
      oestrogen levels results in a corresponding decline in cognitive processing.
      Arguments for an effect are based on findings from laboratory and hormone
      replacement studies and the pharmacological actions of breast cancer drugs.
      However, there are few clinical data substantiating the claim that endocrine
      therapies used in the treatment and prevention of breast cancer could affect
      cognition. This paper examines the main evidence associated with this claim and
      discusses the importance of examining such issues within randomised trials.

PMID- 17499989
TI  - Novel heterocyclic thyromimetics. Part 2.
AB  - Novel heterocyclic thyromimetics are presented carrying carboxy-substituted
      benzofurans or sulfur containing heterocycles, as replacements for the amino acid
      side chain of T3. Potent agonists were identified in both series. SAR trends are
      examined and found to be mostly consistent with previously published
      thyromimetics. The lack of isoform selectivity demonstrated with isoform
      selective transient THR transfection assays has been confirmed by corresponding
      in vivo studies.

PMID- 17499990
TI  - Synthesis and characterization of a perchlorotriphenylmethyl (trityl) triester
      radical: a potential sensor for superoxide and oxygen in biological systems.
AB  - Synthesis and characterization of an inert perchlorotriphenylmethyl triester
      radical, PTM-TE, are reported. PTM-TE was prepared by a facile 3-step synthesis
      using Friedel-Crafts reaction of tetrachlorobenzene with chloroform followed by
      ethoxycarbonylation and subsequent oxidation. PTM-TE is paramagnetic and exhibits
      a single sharp EPR spectrum. In solution, the EPR linewidth of PTM-TE is highly
      sensitive to the dissolved oxygen content, thus enabling accurate measurement of
      oxygen concentration (oximetry). In addition, the radical also shows high
      reactivity towards superoxide. The ester radical has the potential for use as a
      high-sensitive probe for determination of oxygen concentration and superoxide in
      biological systems.

PMID- 17499991
TI  - Endocrine therapy for breast cancer: an overview.
AB  - Endocrine therapy for breast cancer has been established in the adjuvant
      treatment for primary disease and in the treatment of advanced disease. The ER
      remains the best predictor of response although other factors exist and need to
      be identified. Pharmacological manipulation has been replacing ablative
      procedures. Tamoxifen used to be the most popular agent of choice and promising
      new agents include the pure anti-oestrogens and the third generation selective
      aromatase inhibitors. Ongoing and future studies will optimise treatment in
      established areas and will exploit its potential roles in preoperative use and
      chemoprevention.

PMID- 17499992
TI  - Comparisons of the inter-joint coordination between leading and trailing limbs
      when crossing obstacles of different heights.
AB  - Fifteen normal adults walked and crossed obstacles of different heights (10%, 20%
      and 30% of leg length) with each limb while kinematic data were measured to
      obtain joint angles in the sagittal plane. Phase angles of each joint were
      calculated from the angular velocities (x') and displacements (x) as phi=tan(
      1)(x'/x). Relative phase angles were then calculated by subtracting phase angles
      of a distal joint from the proximal joint (phi(hip-knee), phi(knee-ankle)). The
      standard deviations of the relative phase curve points for the stance and swing
      phase for each obstacle height were averaged to obtain the respective deviation
      phase (DP) values. The calculated DP variables were tested using a two-factor
      repeated ANOVA. The leading and trailing limbs were found to have similar
      patterns of inter-joint coordination, but different levels of stability, the
      leading being more stable than the trailing during swing (p<0.05), while only
      leading knee-ankle coordination was less stable than that of the trailing during
      stance (p<0.05). Only the stability of the knee-ankle coordination for both limbs
      decreased with increasing obstacle height during stance (p<0.05). It is suggested
      that clinical obstacle-crossing training programs for patients with unilateral
      pathology should include the training of the affected limb, not only as leading
      but also as trailing limb. An increase of the stability of the ankle joint may be
      helpful for the stability of the knee-ankle coordination and thus for the general
      performance of obstacle-crossing.

PMID- 17499993
TI  - Long-term effect of different treadmill interventions on gait development in new
      walkers with Down syndrome.
AB  - This longitudinal study investigated the long-term effect of different treadmill
      interventions on the development of gait patterns in infants with Down syndrome
      (DS). Thirty infants with DS (mean age 10.0 months, S.D. 1.9 months) were
      randomly assigned to either a "low intensity-generalized" (LG) training group, or
      a "high intensity-individualized" (HI) training group. Treadmill intervention was
      conducted in infants' homes until they walked three steps independently. Twenty
      five participants completed a 1-year gait follow-up after the treadmill
      intervention. Six basic gait parameters were examined: normalized velocity,
      cadence, step length, step width, double support percentage, and dynamic base.
      Principal component analysis (PCA) conducted for the set of the six basic gait
      parameters demonstrated that the first principal component (PC1) accounted for
      83.8% of the variance. A two-way ANOVA with repeated measures conducted with PC1
      scores revealed a significant visit effect and group difference; both groups
      significantly increased PC1 scores over time, and the HI group produced
      significantly higher PC1 scores than the LG group. Specifically, the HI group
      produced significantly higher normalized velocity and cadence, and lower double
      support percentage than the LG group. In addition, both groups significantly
      reduced foot rotation asymmetry over time although no difference was found
      between the two groups. We concluded that the HI treadmill intervention provided
      a better long-term effect on the development of basic gait parameters than the LG
      training, and the reduction of foot rotation asymmetry over time was not
      differentially affected by the different training protocols.

PMID- 17499994
TI  - Postural responses following a rotational support surface perturbation, following
      knee joint replacement: frontal plane rotations.
AB  - Total knee arthroplasty (TKA) is associated with altered sensory and motor
      functions of the knee which may impair balance control when standing and walking.
      This study examined the organization of electromyographic and kinematic postural
      responses to frontal plane support surface rotations, after TKA. Eight TKA
      patients and nine control participants volunteered. Patients demonstrated changes
      in onset latency of rectus femoris and gluteus medius, and in amplitude of muscle
      activity in tibialis anterior, gastrocnemius, rectus femoris, and gluteus medius,
      for both perturbation directions, and for both the surgical and sound limbs. Peak
      knee joint angular velocity was reduced among the patients for both perturbation
      directions and both the surgical and sound limbs, and patients demonstrated
      greater peak center of mass displacement. The CNS appears to alter the response
      to postural perturbation of both lower limbs, based on the reduced capacities of
      the surgical limb. Impaired detection of the valgus-varus loading of the knee
      joints may lead to the changes in muscle activity and resultant kinematics.
      Clinically, these findings are relevant in understanding that fully recovered TKA
      patients may continue to demonstrate balance impairments, and that balance
      training during physical rehabilitation may be advantageous to these patients.

PMID- 17499995
TI  - Modification in reverse: the SUMO proteases.
AB  - SUMOs (small ubiquitin-like modifiers) are ubiquitin-related proteins that become
      covalently conjugated to cellular target proteins that are involved in a variety
      of processes. Frequently, this modification has a key role in regulating the
      activities of those targets and, thus, their cellular functions. SUMO conjugation
      is a highly dynamic process that can be rapidly reversed by the action of members
      of the Ubl (ubiquitin-like protein)-specific protease (Ulp) family. The same
      family of enzymes is also responsible for maturation of newly synthesized SUMOs
      prior to their initial conjugation. Recent advances in structural, biochemical
      and cell biological analysis of Ulp/SENPs reveal their high degree of specificity
      towards SUMO paralogs, in addition to discrimination between processing,
      deconjugation and chain-editing reactions. The dissimilar sub-nuclear
      localization patterns of Ulp/SENPs and phenotypes of Ulp/SENP mutants further
      indicate that different Ulp/SENPs have distinct and non-redundant roles.

PMID- 17499996
TI  - Carbonic anhydrase activators: the first activation study of the human secretory
      isoform VI with amino acids and amines.
AB  - The secretory isozyme of human carbonic anhydrase (hCA, EC 4.2.1.1), hCA VI, has
      been cloned, expressed, and purified in a bacterial expression system. The
      kinetic parameters for the CO(2) hydration reaction proved hCA VI to possess a
      k(cat) of 3.4 x 10(5)s(-1) and k(cat)/K(M) of 4.9 x 10(7)M(-1)s(-1) (at pH 7.5
      and 20 degrees C). hCA VI has a significant catalytic activity for the
      physiological reaction, of the same order of magnitude as the ubiquitous isoform
      CA I or the transmembrane, tumor-associated isozyme CA IX. A series of amino
      acids and amines were shown to act as CA VI activators, with variable efficacies.
      l-His, l-Trp, and dopamine showed weak CA VI activating effects (K(A)s in the
      range of 21-42 microM), whereas d-His, d-Phe, l-DOPA, l-Trp, serotonin, and some
      pyridyl-alkylamines were better activators, with K(A)s in the range of 13-19
      microM. The best CA VI activators were l-Phe, d-DOPA, l-Tyr, 4-amino-l-Phe, and
      histamine, with K(A)s in the range of 1.23-9.31 microM. All these activators
      enhance k(cat), having no effect on K(M), participating thus in the rate
      determining step in the catalytic cycle, the proton transfer reactions between
      the enzyme active site and the environment.

PMID- 17499998
TI  - Single nucleotide specific detection of DNA by native chemical ligation of
      fluorescence labeled PNA-probes.
AB  - DNA-directed chemical ligations provide the opportunity to diagnose DNA sequences
      with very high sequence specificity. Fluorescent labels have been attached to
      reactive probes to enable the homogeneous detection of DNA and RNA. However, it
      has frequently been found that the attachment of fluorescent labels results in
      decreases of ligation fidelity. Herein we describe the development of a
      fluorogenic ligation reaction that provides for 10(2)-fold to perfect sequence
      selectivity. The reaction is based on the isocysteine-mediated native chemical
      PNA ligation. It is shown that DNA-induced rate accelerations of approximately
      43.000-fold can be obtained through subtle variations of the ligation conditions.
      PNA-thioesters and isocysteine-PNA conjugates were labeled with FAM and TMR
      fluorophores, respectively. For gaining rapid synthetic access, a convenient on
      resin labeling approach was developed. A new PNA monomer featuring an Alloc
      protected lysine side chain was synthesized and coupled in solid-phase PNA
      synthesis. In the event of a ligation reaction the two fluorophores are brought
      into proximity. It is shown that fluorescence resonance energy transfer provides
      a positive fluorescence signal which is specific for product formation rather
      than for loss of starting materials. Single base mutations can be detected within
      minutes and with very high sequence selectivity at optimized conditions.

PMID- 17499997
TI  - The anti-androgen effect of ganoderol B isolated from the fruiting body of
      Ganoderma lucidum.
AB  - The anti-androgenic activity of the ethanol extract of the fruiting body of
      Ganoderma lucidum has been previously reported. Ganoderol B with 5alpha-reductase
      inhibitory activity and the ability to bind to androgen receptor (AR) can inhibit
      androgen-induced LNCaP cell growth and suppress regrowth of the ventral prostate
      induced by testosterone in rats. The down-regulation of AR signaling by ganoderol
      B provides an important mechanism for its anti-androgenic activity. In view of
      the fact that PSA (prostatic specific antigen, a well-accepted prognostic
      indicator of prostate cancer) is down-regulated, an important implication of this
      study is that ganoderol B intervention strategy aimed at toning down the
      amplitude of androgen signaling could be helpful in controlling morbidity of
      prostate cancer. In conclusion, our result suggests that ganoderol B might be
      useful in prostate cancer and benign prostatic hyperplasia (BPH) therapy through
      suppressing the function of androgen and its receptor.

PMID- 17499999
TI  - A single prophylactic dose of pentoxifylline reduces high dependency unit time in
      cardiac surgery - a prospective randomized and controlled study.
AB  - BACKGROUND: The pathogenesis of the post cardiopulmonary bypass (CPB) organ
      dysfunction syndrome is complex, with inflammation being an important component.
      The purpose of this prospective, randomized and controlled study was to evaluate
      the effect of a single dose of pentoxifylline (PTX) prior to CPB on high
      dependency unit time. MATERIALS AND METHODS: We studied 39 patients undergoing
      aorto-coronary bypass surgery with CPB. Patients received either 5 mg kg(-1) PTX
      after induction of anaesthesia or saline as placebo. Haemodynamics, parameters of
      pulmonary function and plasma levels of tumour necrosis factor alpha (TNFalpha)
      and C-reactive protein (CRP) were measured after the induction of anaesthesia
      (pre-CPB) and after weaning from CPB (post-CPB), 1 h after the admission to the
      intensive care unit (ICU) and on the morning of the first postoperative day (1
      POD), respectively. In addition, ventilation time and the high dependency unit
      time, i.e. the time till transferral to a peripheral ward, were documented.
      RESULTS: Patients in the PTX group had lower TNFalpha values (6.3 ng ml(-1)
      (4/8.2) vs 9.1 ng ml(-1) (6.5/13.7)) (median (25%/75%), p=0.021), lower systolic
      (28+/-7 mm Hg vs 35 +/- 9 mm Hg, mean+/-SD, p=0.011) and mean pulmonary artery
      pressures (21+/-5 vs 26+/-6 mm Hg, p=0.017) after admission to the ICU than
      control patients. Haemodynamics and pulmonary function parameters did not differ.
      There was a trend towards earlier weaning from the respirator in the PTX group
      (10.0+/-3.5 h) (min/max: 4/16; confidence interval (ConF): 1.8 h) than the
      control group (12.3+/-4.2 h) (min/max: 5-24; ConI: 2.4 h) (p=0.077). Patients
      treated with PTX could be transferred to a peripheral ward about 24 h earlier
      than control patients (95+/-35 h, min/max: 32/190 h; ConI: 17 h; 119+/-29 h,
      min/max: 66/165 h; ConI: 16 h) respectively; p=0.037). CONCLUSION(S): A single
      dose of PTX prior to CPB was able to reduce plasma levels of TNFalpha. In this
      descriptive study, there was a trend towards reduced duration of ventilation and
      the high dependency unit time, i.e. the time till transferral to a peripheral
      ward was shortened.

PMID- 17500000
TI  - Effect of recombinant aprotinin on postoperative blood loss and coronary vascular
      function in a canine model of cardiopulmonary bypass.
AB  - OBJECTIVE: Aprotinin is a widely used serine protease inhibitor during
      cardiopulmonary bypass to reduce blood loss and preserve platelet function.
      However, the bovine-derived aprotinin can induce hypersensitivity reaction with
      fatal complications. Furthermore, vascular effects of aprotinin are not
      completely elucidated. The current study is designed to investigate the effects
      of recently developed recombinant aprotinin on blood loss and coronary vascular
      function in a clinically relevant canine model of cardiopulmonary bypass without
      aortic cross-clamping and cardioplegia. METHODS: Twenty-four dogs underwent
      cardiopulmonary bypass without aortic cross-clamping and cardioplegia. Dogs were
      divided into three groups in a blinded fashion: control animals (n=8) received
      placebo, aprotinin treatment groups received bovine (n=8) or recombinant
      aprotinin (n=8) according to the Hammersmith method. The doses of bovine and
      recombinant aprotinin were the same. Coagulation parameters and blood loss were
      measured regularly at different time points. Endothelium-dependent and 
      independent vasorelaxation were investigated in isolated left anterior descendent
      coronary arterial rings by using acetylcholine and bradykinin or sodium
      nitroprusside and adenosine, respectively. RESULTS: Postoperative blood loss was
      significantly reduced in the aprotinin-treated groups in comparison to control
      and there was no significant difference between the two aprotinin-treated groups.
      Endothelium-dependent relaxation of coronary arteries to acetylcholine and
      bradykinin was unaffected in the aprotinin treatment groups. Both types of
      aprotinin significantly increased vasorelaxation to adenosine when compared with
      controls, but did not affect that to sodium nitroprusside. CONCLUSIONS: The
      effectiveness of recombinant aprotinin on blood loss was equivalent to bovine
      derived aprotinin. Neither types of aprotinin impaired endothelium-dependent
      relaxation in a canine model of cardiopulmonary bypass.

PMID- 17500001
TI  - Two cases of intra-pericardial tumors arising from the ascending aorta in adults.
AB  - Two female patients aged 64 and 50 years, who had intra-pericardial tumors
      arising from the ascending aorta, are reported. Both patients were admitted with
      mediastinal mass. Surgery was performed by median sternotomy with complete
      excision. Histology revealed teratoma and ectopic thyroid. Tumors arising from
      the ascending aorta are very rare and should be considered in the differential
      diagnosis of the mediastinal masses.

PMID- 17500002
TI  - Significance of malperfusion syndromes prior to contemporary surgical repair for
      acute type A dissection: outcomes and need for additional revascularizations.
AB  - OBJECTIVE: The aim of this study was to assess the significance of malperfusion
      syndromes in patients with acute type A aortic dissection following a
      contemporary surgical management algorithm and the effects on morbidity, hospital
      mortality, and long-term survival. We believe that obliteration of the primary
      tear site with restoration of flow in the true aortic lumen results in decreased
      need for revascularization of malperfused organ systems. METHODS: Our operative
      approach aims at replacing the entire ascending aorta, resuspension of the aortic
      valve with repair or replacement of the sinus segment, and routine open
      replacement of the arch under hypothermic circulatory arrest with retrograde
      cerebral perfusion with obliteration of false lumen at the distal arch/proximal
      descending thoracic aorta, thus reestablishing normal flow in the descending
      thoracic true lumen. From January 1993 to December 2004, 221 consecutive patients
      underwent repair of acute type A aortic dissection at our institution. Data were
      collected retrospectively and prospectively. Various types of malperfusion
      syndromes were present in 26.7% of patients. The organ systems with malperfusion
      were as follows: cardiac, 7.2%; cerebral, 7.2%; ileofemoral, 12.7%; renal, 4.1%;
      mesenteric, 1.4%; innominate, 5.4%; and spine, 2.2%. RESULTS: Coronary
      malperfusion required coronary revascularization in 62.5% of cases. Distal
      revascularization was needed in 42.9% of patients with ileofemoral malperfusion.
      Patients with malperfusion were more likely to suffer perioperative myocardial
      infarction (p<0.001), postoperative coma (p=0.012), delirium (p=0.011), sepsis
      (p=0.006), acute renal failure (p=0.017), dialysis (p=0.018), and acute limb
      ischemia (p<0.001). The in-hospital mortality was 30.5% in patients presenting
      with any malperfusion syndrome while only 6.2% in patients without malperfusion
      syndrome (p<0.001). Both cardiac (p=0.020) and cerebral malperfusions (p<0.001)
      were risk factors for in-hospital mortality. The actuarial long-term survival in
      patients with malperfusion syndrome was estimated by Kaplan-Meier methods to be
      67.8%+/-6.1% at 1 year, 54.0%+/-7.0% at 5 years, and 43.1%+/-8.0% at 10 years and
      for patient without malperfusion 82.7%+/-3.0% at 1 year, 66.3%+/-3.9% at 5 years,
      and 46.1%+/-6.7% at 10 years (log rank 2.55, p=0.110). Cerebral malperfusion was
      a significant risk factor for decreased long-term survival (p=0.0002).
      CONCLUSIONS: The occurrence of malperfusion in patients with acute type A
      dissection is associated with significant increased risk of in-hospital mortality
      and complications. Additional revascularization is generally needed in patients
      with coronary malperfusion and ileofemoral malperfusion. Patients presenting with
      cardiac and cerebral malperfusions have a high hospital mortality and
      preoperative cerebral malperfusion is associated with dismal long-term survival.

PMID- 17500004
TI  - A surgeon's case volume of oesophagectomy for cancer strongly influences the
      operative mortality rate.
AB  - OBJECTIVE: To assess if individual case volume of oesophagectomy for cancer
      influences the risk of mortality and long-term survival. METHODS: Between January
      1994 and December 2005, 195 resections for oesophageal cancer were performed by
      nine surgeons in a single institution. Operative mortality, defined as in
      hospital death, was compared between the high-volume and low-volume surgeons.
      Multivariate logistic regression was used to analyze the risk factors for death
      between the two groups, also in the presence of covariates. RESULTS: There were
      140 males and 55 females with mean age of 63.4 (32-84). Two high-volume surgeons
      performed 61% (118) of the operations with a mean of 11 per year compared to 4
      per year in the low-volume group. The patients in the two groups were matched for
      age (63 years vs 64; p=0.53), sex (67 vs 79% male; p=0.07). Ivor Lewis resections
      were performed more frequently by high-volume surgeons (95 vs 73%; p<0.001). The
      operative mortality rate was much lower when high case volume surgeons performed
      the procedure (4 vs 17%; p=0.001). The relative risk of death when low-volume
      surgeons performed the procedure was 4.59 (95% CI 1.57-13.46; p<0.001). In
      hospital mortality was significantly associated with low-volume surgeon when
      controlling separately for age (OR 4.60; 95% CI 1.55, 13.60, p=0.006), tumor
      stage (OR 3.76; 95% CI 1.24, 11.45, p=0.02) and tumor type (OR 3.87; 95% CI 1.29,
      11.60, p=0.016). Kaplan-Meier curves comparing the survival of high- and low
      volume surgeons showed no statistical differences (Log rank p=0.48). CONCLUSIONS:
      Operative mortality rate for oesophagectomy for cancer is strongly influenced by
      case volume and was 4.6-fold higher when performed by surgeons with low case
      volume. Patients with oesophageal cancer in need of an oesophagectomy may benefit
      from referral to a high-volume thoracic surgeon.

PMID- 17500005
TI  - Should axillary artery to coronary artery bypass be part of the cardiac surgeon's
      armamentarium?
AB  - BACKGROUND: The axillary artery has been used as an alternate inflow source for
      revascularization of the lower extremities for four decades. Since 1997, there
      have been several reports of axillary artery to coronary artery bypass. METHODS:
      All cases of axillary artery to coronary artery bypass at our institution from
      1997 through 2003 were reviewed. PubMed was queried for publications on this
      subject and all pertinent reports were reviewed. RESULTS: Thirty-eight patients
      underwent axillary artery to coronary artery bypass at our hospital. Most (34) of
      the operations were performed without cardiopulmonary bypass. Saphenous vein (37)
      or radial artery (1) grafts were placed to one or more coronary arteries from
      either the left (36) or right (2) axillary artery. Twenty patients underwent
      sternotomy, and 18 had either a left (16) or right (2) minimally invasive direct
      coronary artery bypass (MIDCAB) procedure performed. Most of the sternotomies
      were for primary myocardial revascularization and most of the MIDCABs were
      reoperations. There were three deaths-all from non-cardiac causes, one myocardial
      infarction, and one transient brachial plexus injury. Doppler ultrasound,
      angiographic, and clinical follow-up were limited, but graft patency has been
      demonstrated up to 9 years. CONCLUSION: Axillary artery to coronary artery bypass
      should be part of the armamentarium of surgeons who perform myocardial
      revascularization operations.

PMID- 17500006
TI  - Mitochondria as key components of the stress response.
AB  - The exquisitely orchestrated adaptive response to stressors that challenge the
      homeostasis of the cell and organism involves important changes in mitochondrial
      function. A complex signaling network enables mitochondria to sense internal
      milieu or environmental changes and to adjust their bioenergetic, thermogenic,
      oxidative and/or apoptotic responses accordingly, aiming at re-establishment of
      homeostasis. Mitochondrial dysfunction is increasingly recognized as a key
      component in both acute and chronic allostatic states, although the extent of its
      role in the pathogenesis of such conditions remains controversial. Genetic and
      environmental factors that determine mitochondrial function might contribute to
      the significant variation of the stress response. Understanding the often
      reciprocal interplay between stress mediators and mitochondrial function is
      likely to help identify potential therapeutic targets for many stress and
      mitochondria-related pathologies.

PMID- 17500007
TI  - Analysis of protein mixtures by electrospray mass spectrometry: effects of
      conformation and desolvation behavior on the signal intensities of hemoglobin
      subunits.
AB  - The determination of solution-phase protein concentration ratios based on ESI-MS
      intensity ratios is not always straightforward. For example, equimolar mixtures
      of hemoglobin alpha- and beta-subunits consistently result in much higher peak
      intensities for the alpha-chain. The current work explores the origin of this
      effect. Under mildly acidic conditions (pH 3.4) alpha-globin is extensively
      unfolded, whereas beta-globin retains residual structure. Because of its greater
      nonpolar character, the more unfolded alpha-subunit can more effectively compete
      for charge. This leads to suppression of beta-globin signals under conditions
      where the protein ion yield is limited by the charge concentration on the
      initially formed ESI droplets. More balanced intensities are observed when
      operating under charge excess conditions and/or in a solvent environment where
      both proteins are unfolded to a similar degree (pH 2.2). However, even in these
      cases the overall alpha-globin peak intensity is still twice as high as that of
      the beta-subunit. The persistent imbalance under these conditions originates from
      the different declustering behaviors of the two proteins. A considerable fraction
      of beta-globin undergoes incomplete desolvation during ESI, thereby reducing the
      intensity of bare [beta + zH](z+) ions. When including the contributions of
      incompletely desolvated species, the overall alpha:beta ion intensity ratio is
      close to unity. The alpha:beta intensity imbalance can also be eliminated by a
      strongly elevated declustering potential in the ion sampling interface. In
      conclusion, important factors that have to be considered for the ESI-MS analysis
      of protein mixtures are (1) conformational effects, resulting in differential
      surface activities, and (2) dissimilarities in the protein desolvation behavior.

PMID- 17500008
TI  - Biochemical and mass spectrometric characterization of the human CB2 cannabinoid
      receptor expressed in Pichia pastoris--importance of correct processing of the N
      terminus.
AB  - This study was conducted to optimize the expression of human CB2 cannabinoid
      receptors in methylotrophic yeast Pichia pastoris (P. pastoris). Two major
      species of expressed CB2 proteins were seen on Western blot, i.e., a 42 kDa band
      which matches the calculated molecular weight for tagged CB2, and a 52/55 kDa
      doublet. Treatment of membranes with N-glycosidase F or inclusion of tunicamycin
      in the culture medium during induction resulted in the disappearance of the 55
      kDa, but not the 52 kDa band, suggesting that the 3 kDa extra in the 55 kDa band
      is due to N-glycosylation, but the 10 kDa extra in the 52 kDa band is not due to
      N-glycosylation. Anti-FLAG M1 antibody had a much higher preference for the 42
      kDa band over the 52/55 kDa doublet, and a 10 kDa fragment recognized by anti
      FLAG M2 antibody was generated by CNBr digestion of the 52/55 doublet. These data
      strongly support the hypothesis that the 10 kDa increase in molecular weight was
      due to unprocessed alpha-factor sequence. This conclusion was further validated
      by finding several peptide sequences for alpha-factor fragments at the N-terminal
      of the CB2 receptor using pepsin/chymotrypsin digestion and LC/MS/MS approaches.
      Importantly, unprocessed alpha-factor was found to be associated with poor ligand
      binding. In addition, controlling the level of CB2 protein expression was found
      to be critical for minimizing the presence of unprocessed alpha-factor sequence.
      The information gained from this study should aid the proper expression of not
      only CB2 receptor but also other members of the GPCR family in P. pastoris.

PMID- 17500010
TI  - Early electrophysiological responses to multiple face orientations correlate with
      individual discrimination performance in humans.
AB  - Picture-plane inversion dramatically impairs face recognition. Behavioral and
      event-related potential (ERP) studies suggest that this effect takes place during
      perceptual encoding of the face stimulus. However, the relationship between early
      electrophysiological responses to upright and inverted faces and the behavioral
      face inversion effect remains unclear. To address this question, we recorded ERPs
      while presenting 10 subjects with face photographs at 12 different orientations
      around the clock (30 degrees steps) during an individual face matching task.
      Using the variability in the electrophysiological responses introduced by the
      multiple orientations of the target face, we found a correlation between the ERP
      signal at 130-170 ms on occipito-temporal channels, and the behavioral
      performance measured on the probe stimulus. Correlations between ERP signal and
      behavioral performance started about 10 ms earlier in the right hemisphere.
      Significant effects of orientation were observed already at the level of the
      visual P1 (peaking at 100 ms), but the ERP signal was not correlated with
      behavior until the face-sensitive N170 time window. Overall, these observations
      indicate that plane-inversion affects the perceptual encoding of faces as early
      as 130 ms in occipito-temporal regions, leading directly to an increase in error
      rates and RTs during individual face recognition.

PMID- 17500009
TI  - Time course of semantic processes during sentence comprehension: an fMRI study.
AB  - The ability to create new meanings from combinations of words is one important
      function of the language system. We investigated the neural correlates of
      combinatorial semantic processing using fMRI. During scanning, participants
      performed a rating task on auditory word or pseudoword strings that differed in
      the presence of combinatorial and word-level semantic information. Stimuli
      included normal sentences comprised of thematically related words that could be
      readily combined to produce a more complex meaning, semantically incongruent
      sentences in which content words were randomly replaced with other content words,
      pseudoword sentences, and versions of these three sentence types in which
      syntactic structure was removed by randomly re-ordering the words. Several
      regions showed greater BOLD signal for stimuli with words than for those with
      pseudowords, including the left angular gyrus, left superior temporal sulcus, and
      left inferior frontal gyrus, suggesting that these areas are involved in semantic
      access at the single word level. In the angular and inferior frontal gyri these
      differences emerged early in the course of the hemodynamic response. An effect of
      combinatorial semantic structure was observed in the left angular gyrus and left
      lateral temporal lobe, which showed greater activation for normal compared to
      semantically incongruent sentences. These effects appeared later in the time
      course of the hemodynamic response, beginning after the entire stimulus had been
      presented. The data indicate a complex spatiotemporal pattern of activity
      associated with computation of word and sentence-level semantic information, and
      suggest a particular role for the left angular gyrus in processing overall
      sentence meaning.

PMID- 17500012
TI  - Cryptic genetic divergence and associated morphological differentiation in the
      arboreal land snail Satsuma (Luchuhadra) largillierti (Camaenidae) endemic to the
      Ryukyu Archipelago, Japan.
AB  - Land snails are renowned model organisms in evolutionary ecology, but extensive
      morphological variation and lack of readily available diagnostic characters often
      invite taxonomic confusion among closely related species. Satsuma (Luchuhadra)
      largillierti is an arboreal land snail endemic to Okinawa Island, Japan, in which
      extensive geographic variation in shell morphology has long caused taxonomic
      complication. To establish robust species limits among S. largillierti and its
      allies, we perform molecular and morphological analyses of snails sampled from
      the entire range of Luchuhadra. Analyses of the mitochondrial cytochrome oxidase
      subunit 1 gene and nuclear ribosomal internal transcribed spacer sequences divide
      S. largillierti into two, reproductively isolated groups. Each of these groups
      includes Satsuma erabuensis and Satsuma sooi, respectively, which occur on a
      nearby island and were traditionally regarded as distinct species. Morphometric
      analysis of the genitalia further provides clear difference between the two
      groups, whereas differentiation in shell morphology is slight if any. These
      results indicate that the traditional taxonomy has overly depended on inadequate
      morphological difference and a priori information of island geography, which
      resulted in oversimplification of complex speciation history in Luchuhadra.

PMID- 17500011
TI  - Multigenic and morphometric differentiation of ground squirrels (Spermophilus,
      Scuiridae, Rodentia) in Turkey, with a description of a new species.
AB  - This study reports on the molecular phylogenetics of ground squirrels, genus
      Spermophilus, in Turkey using cytochrome b (1140bp), part of the D-loop and
      flanking tRNAs (572bp), X chromosome (867-1051bp) and Y chromosome (983-989bp)
      DNA sequences. Individuals also were characterized by karyotype and with
      geometric morphometric analyses of mandibles and skulls. Two hundred fourteen
      individuals from 91 localities were studied. All the data support the recognition
      of a new species in SW Anatolia: the Taurus ground squirrel Spermophilus
      taurensis sp. nov. The new species has a small distribution in the Taurus
      Mountains in an area that is a hotspot for biodiversity. Molecular clock analysis
      suggests that the new species diverged from the European ground squirrel,
      Spermophilus citellus, about 2.5 million years ago and that the ancestor of these
      two species diverged from the widespread Anatolian ground squirrel, Spermophilus
      xanthoprymnus, about 5 million years ago. Morphometric differentiation in skull
      and mandible shape among the three species is incomplete, but statistically
      significant. S. xanthoprymnus is subdivided into five cytochrome b phylogroups
      and we use these data to infer the location of glacial refugia where the species
      lived during the last glacial maximum. This study illustrates the potential of
      combined molecular and morphometric studies to uncover new Anatolian species and
      to reconstruct their phylogeographic history. The new species is important for
      squirrel taxonomy and for understanding Eurasian mammal evolution.

PMID- 17500013
TI  - Species polyphyly and mtDNA introgression among three Serrasalmus sister-species.

PMID- 17500014
TI  - Transcriptional profiling and pathway analysis of monosodium iodoacetate-induced
      experimental osteoarthritis in rats: relevance to human disease.
AB  - OBJECTIVE: The objective of this study was to characterize the rat monosodium
      iodoacetate (MIA)-induced model for osteoarthritis (OA) and determine the
      translatability of this model to human disease. This was accomplished through
      pathway, network and system level comparisons of transcriptional profiles
      generated from animal and human disease cartilage. METHODS: An OA phenotype was
      induced in rat femorotibial joints following a single injection of 200mug MIA per
      knee joint for a period of 2 or 4 weeks. Lesion formation in the rat joints was
      confirmed by histology. Gene expression changes were measured using the Agilent
      rat whole genome microarrays. Cartilage was harvested from human knees and gene
      expression changes were measured using the Agilent human arrays. RESULTS: One
      thousand nine hundred and forty-three oligos were differentially expressed in the
      MIA model, of these, approximately two-thirds were up-regulated. In contrast, of
      the 2130 differentially expressed oligos in human disease tissue, approximately
      two-thirds were down-regulated. This dramatic difference was observed throughout
      each level of the comparison. The total overlap of genes modulated in the same
      direction between rat and human was less than 4%. Matrix degradation and
      inflammatory genes were differentially regulated to a much greater extent in MIA
      than human disease tissue. CONCLUSION: This study demonstrated, through multiple
      levels of analysis, that little transcriptional similarity exists between rat MIA
      and human OA derived cartilage. As disease modulatory activities for potential
      therapeutic agents often do not translate from animal models to human disease,
      this and like studies may provide a basis for understanding the discrepancies.

PMID- 17500015
TI  - Actinobacillus actinomycetemcomitans adheres to human gingival fibroblasts and
      modifies cytoskeletal organization.
AB  - Adherence of Actinobacillus actinomycetemcomitans to human gingival fibroblast
      cells induces cytoskeletal reorganization. A. actinomycetemcomitans is considered
      a pathogenic bacteria involved in localized aggressive periodontitis. Studies
      with epithelial cells have shown an adherent capacity of bacteria that is
      increased under anaerobic conditions. For adherence to take place, there is a
      need for interaction between extracellular vesicles and bacterial fimbriae.
      However, molecular events associated with the adherence process are still
      unknown. The aim of this study was to investigate whether A.
      actinomycetemcomitans adherence to human gingival fibroblasts promotes
      cytoskeletal reorganization. Adherence was determined with light microscopy and
      scanning electron microscopy. For F-actin visualization, cells were treated with
      fluorescein-isothiocyanate-phalloidin and samples were examined with
      epifluorescence optics. Fluorescent was recorded on Kodak T-Max 400 film. We
      showed that A. actinomycetemcomitans adheres to human gingival fibroblast primary
      cultures, this property stimulating an increase in the intracellular calcium
      levels. In human gingival fibroblast primary cultures, we observed that maximal
      A. actinomycetemcomitans adherence took place 1.5h after culture infection
      occurred and remained for 6h. The adherence was associated with morphologic
      alterations and an increased in the intracellular calcium levels. These
      experiments suggest that A. actinomycetemcomitans adherence cause morphological
      alterations, induce actin stress fibers and recruitment of intracellular calcium
      levels.

PMID- 17500016
TI  - The Aspergillus nidulans putative kinase, KfsA (kinase for septation), plays a
      role in septation and is required for efficient asexual spore formation.
AB  - In Aspergillus nidulans nuclear division and cytokinesis are coupled processes
      during asexual sporulation. Metulae, phialides and conidia contain a single
      nucleus. Here we describe the role of a putative Saccharomyces cerevisiae Kin4
      related kinase, KfsA (kinase for septation) in the control of septum formation in
      A. nidulans. The kfsA deletion caused an increase in the number of conidiophores
      with septa in their stalks from 20% in wild type to 60% in the mutant strain.
      Interestingly, 7% of metulae contained two nuclei and the corresponding phialides
      remained anucleate, suggesting septum formation before proper segregation of
      nuclei. This points to a checkpoint control of KfsA, which prevents septum
      formation before nuclear separation. KfsA localized to the cortex and septa in
      hyphae and in conidiophores but not to the spindle-pole bodies, as it was shown
      for Kin4 in yeast. KfsA appeared at septa after actin disappeared, suggesting an
      additional role of KfsA late during septum formation.

PMID- 17500017
TI  - Cartilage canals in the medial coronoid process of young Golden Retrievers.
AB  - The aim of the study was to establish the location of cartilage canals in the
      medial coronoid process (MCP) of the ulna of young Golden Retrievers, a breed
      that is predisposed to fractures of the medial coronoid process (FMCP). To
      determine whether the presence of cartilage canals could be associated with the
      predilection site of FMCP, the right elbows of nine young Golden Retrievers (aged
      4, 6, 8, 10, 13, 16, 18, 22 and 24 weeks) were dissected and, with no prior
      decalcification, the formaldehyde-fixed MCPs were embedded in methylmethacrylate.
      The entire MCPs were serially sectioned in the frontal plane from cranial to
      caudal and the sections (5 microm) were routinely stained. Between the ages of 5
      and 10 weeks, three main cartilage canals were visible--medial, central and
      lateral. All originated from the periosteum of the distal parts of the MCP and
      ended proximally under the articular cartilage. Branches of the main canals were
      seen more cranially and caudally. At the age of 13 weeks, the central canal was
      absent, and the remaining canals showed a smaller diameter. From 16 weeks
      onwards, no cartilage canals were seen. No direct relationship could be
      established between the predilection site of FMCP (lateral part of the MCP) and
      the presence/absence of cartilage canals, since both medial and lateral canals
      disappeared at the same age. Further research is needed to elucidate the
      pathogenesis of FMCP.

PMID- 17500018
TI  - Typical absence epilepsy presenting prior to age of 3 years: an uncommon form of
      idiopathic generalized epilepsy.
AB  - PURPOSE: An attempt to allocate patients with the clinical features and
      electroencephalography (EEG) abnormalities of typical absence epilepsy presenting
      before the age of 3 years, similar to childhood and juvenile absence epilepsy
      (JAE) and delineate the clinical manifestations, EEG abnormalities, therapy and
      outcome of such an epileptic disorder by conducting a nationwide survey. RESULTS:
      Overall, eight infants, six males and two females, abided by the inclusion
      criteria of typical absence epilepsy: They were born after an unremarkable
      pregnancy and labor presenting at the age of 12-34 months (mean: 19.6 months)
      with frequent absences time-linked with an EEG demonstrating generalized
      occasionally irregular epileptiform discharges of 3-4 Hz spike/wave and normal
      background activity along with an electrographic photosensitive response in one
      patient. Neurological examination was intact in all infants. All eight infants
      were initially treated with valproic acid, of whom seven immediately responded
      and one had increase in frequency and duration of absences completely aborted
      with treatment of lamotrigine. Three relapsed after termination of therapy of
      whom two again presented with recurrent absences and another one with generalized
      tonic-clonic seizures and as such these children had virtually transformed into a
      later form of idiopathic generalized epilepsy (IGE) during childhood. All eight
      patients are seizure-free, seven still on therapy; seven children within a follow
      up period of 2-7 years and the most recently diagnosed infant for 6 months.
      Cognitive skills were found normal in all children within the low normal range in
      three children with short attention and concentration spans. CONCLUSION: The data
      presented here delineate a very rare form of idiopathic benign generalized
      epilepsy presenting with typical absences before age of 3 years and a favorable
      outcome, similar to childhood and JAE, recognized as distinct IGE syndromes by
      the International League Against Epilepsy (ILAE) classification.

PMID- 17500019
TI  - Improved diffusion measurement in heterogeneous systems using the magic
      asymmetric gradient stimulated echo (MAGSTE) technique.
AB  - A magic asymmetric gradient stimulated echo (MAGSTE) sequence was recently
      proposed to improve molecular diffusion measurements in the presence of spatially
      varying background gradients. Its effectiveness has been demonstrated previously
      with simulated background gradients and in phantoms that contain bulk
      susceptibility differences. In this study, we investigated the MAGSTE technique
      in microscopically heterogeneous systems, and compared it with the conventional
      bipolar pulsed gradient stimulated echo (bPGSTE) sequence. We demonstrated that
      the MASGTE measurements, compared to the bPGSTE method, varied significantly less
      when the diffusion encoding/decoding interval (delta) was changed. In addition,
      the MAGSTE technique provided good characterization of the surface area-to-volume
      ratio for heterogeneous systems investigated in this study. In sum, this study
      showed that the MAGSTE technique provided diffusion measurements superior to
      those of the bPGSTE sequence, especially in the presence of severe heterogeneous
      background gradients.

PMID- 17500020
TI  - A double blind randomised placebo controlled pilot study of oral co-trimoxazole
      in advanced fibrotic lung disease.
AB  - BACKGROUND: In 1996, clinical improvement with oral co-trimoxazole was noted in a
      patient with biopsy proven advanced fibrotic lung disease who was awaiting a lung
      transplant. Subsequently, 14 patients with end stage fibrotic lung disease also
      responded to oral co-trimoxazole. This prompted a double blind randomised placebo
      controlled pilot study in patients with advanced stages of idiopathic
      interstitial pneumonias (IIP) to objectively measure benefit. PATIENTS: Twenty
      patients (aged 49-84 years; 11 males) with progressive fibrotic lung disease who
      had differing subtype diagnosis from CT scans of progressive fibrotic IIP, and
      showed oxygen desaturation on exertion were selected. METHOD: A detailed
      assessment of arterial gases, lung function, and progressive shuttle-walking
      tests combined with oxygen saturation monitoring. Quality of life data was
      recorded. Randomisation was to co-trimoxazole or identical placebo for 3 months
      followed by 6 weeks of pulmonary rehabilitation before decoding. Placebo patients
      received active treatment upon decoding with continued follow up of all patients.
      MAIN OUTCOME MEASURES: Primary 1. Shuttle walking test. Secondary 2. FVC and
      quality of life. RESULTS: Active treatment showed a significant improvement in
      shuttle walking test from 255 to 355 m (p=0.002) (95% CI 200-450) with reduced
      oxygen desaturations during exercise (p=0.003). FVC improved on treatment (+21%)
      from median 1.9 to 2.3 L (p=0.05) (95% CI 1.3-3.0) but TLC and DLCO were not
      significantly changed although stable at 12 months. The MRC 5 Point Dyspnoea
      Score showed improvement (p=0.05) at 3 months for the active group which was
      maintained at 12 months. The SGHRQ showed a significant reduction in symptom
      scores at 12 months (p=0.05). The placebo group showed no significant change in
      any parameters, but demonstrated identical improvement following oral co
      trimoxazole. Serum vascular endothelial growth factor (VEGF) was reduced 50% in
      the active group at 3 months, but just failed to reach statistical significance.
      'Out of study' HRCT scans in 12 patients showed significant reduction in ground
      glass changes (p=0.05) after 12 months of continuous co-trimoxazole treatment.
      CONCLUSION: The findings of the pilot study show significant improvements in
      objective and subjective parameters which fulfil the ATS/ERS (2000) criteria of
      'a favourable response to treatment'.

PMID- 17500021
TI  - A metabolic and genomic study of engineered Saccharomyces cerevisiae strains for
      high glycerol production.
AB  - Towards a global objective to produce chemical derivatives by microbial
      processes, this work dealt with a metabolic engineering of the yeast
      Saccharomyces cerevisiae for glycerol production. To accomplish this goal,
      overexpression of GPD1 was introduced in a tpi1delta mutant defective in triose
      phosphate isomerase. This strategy alleviated the inositol-less phenotype of this
      mutant, by reducing the levels of dihydroxyacetone phosphate and glycerol-3-P,
      two potent inhibitors of myo-inositol synthase that catalyzes the formation of
      inositol-6-phosphate from glucose-6-phosphate. Further deletion of ADH1 and
      overexpression of ALD3, encoding, respectively, the major NAD+-dependent alcohol
      dehydrogenase and a cytosolic NAD+-dependent aldehyde dehydrogenase yielded a
      yeast strain able to produce 0.46 g glycerol (g glucose)(-1) at a maximal rate of
      3.1 mmol (g dry mass)(-1) h(-1) in aerated batch cultures. At the metabolic
      level, this genetic strategy shifted the flux control coefficient of the pathway
      to the level of the glycerol efflux, with a consequent intracellular accumulation
      of glycerol that could be partially reduced by the overproduction of glycerol
      exporter encoded by FPS1. At the transcriptomic level, this metabolic
      reprogramming brought about the upregulation of genes encoding NAD+/NADP+ binding
      proteins, a partial derepression of genes coding for TCA cycle and respiratory
      enzymes, and a downregulation of genes implicated in protein biosynthesis and
      ribosome biogenesis. Altogether, these metabolic and molecular alterations stand
      for major hurdles that may represent potential targets for further optimizing
      glycerol production in yeast.

PMID- 17500022
TI  - [Murine models of platelet diseases].
AB  - Platelet-related diseases correspond to functional defects or abnormal production
      (thrombopoiesis) of hereditary and immunological origins. Recent progress in the
      manipulation of the mouse genome (transgenesis, gene inactivation or insertion)
      has resulted in the generation of numerous strains exhibiting defective platelet
      function or production. Some strains reproduce known hereditary diseases
      affecting haemostasis (Glanzmann thrombasthenia, Bernard-Soulier syndrome (BSS)
      or thrombopoiesis (Wiscott-Aldrich or May-Hegglin syndrome). More often the
      mutated strains have no human equivalent and represent useful models to study:
      (i) the role of adhesive or signalling receptors or of signalling proteins in
      platelet-dependent haemostasis and thrombosis or; (ii) to study the poorly
      characterized mechanisms of thrombopoiesis, which implicate transcription factors
      (GATA, Fli1), growth factors and receptors (TPO, cMPL), and cytoskeletal or
      contractile proteins (tubulin, myosin). Additional mouse strains result from the
      selection of spontaneous mutants many of which affect intracellular platelet
      granules, representing models of storage pool diseases (SPD) such as the Gray
      platelet syndrome (alphaSPD) or Hermansky-Pudlack syndrome (deltaSPD). More
      recently, a systematic chemical mutagenesis approach has also identified genes
      involved in thrombopoiesis and platelet survival. Finally, mouse models of auto-
      or allo-immune thrombocytopenia have been developed to study the mechanisms of
      platelet destruction or removal.

PMID- 17500023
TI  - [Blood transfusion through history, literature and arts].

PMID- 17500024
TI  - Deciphering the glycocode: the complexity and analytical challenge of glycomics.
AB  - Carbohydrates coat most types of cell in nature and are intimately involved in
      various biological events, including cell differentiation, homing to specific
      tissues, cell adhesion, cell recognition, microbial pathogenesis and
      immunological recognition. Carbohydrate structures are complex to analyze owing
      to their branched nature, the diversity of secondary modifications of monomers,
      their indirect relationship to the genome and the range of molecular contexts in
      which the modifications are found. Thus, whereas the fields of genomics and
      proteomics have become accessible to most scientists, technologies to assess
      glycan structures rapidly (i.e. glycomics) are still in the developmental stages.
      This review focuses on recent developments in glycomic technologies, including
      new high-throughput techniques for glycan purification and annotation that are
      advancing mass-spectrometry-based glycomics, and the latest work on microarray
      methodologies to decipher the glycome.

PMID- 17500025
TI  - Microarrays in infection and immunity.
AB  - Over the past decade, microarrays have revolutionized the scientific world as
      dramatically as the internet has changed everyday life. From the initial
      applications of DNA microarrays to uncover gene expression patterns that are
      diagnostic and prognostic of cancer, understanding the interplay between immune
      responses and disease has been a prime application of this technology. More
      recent efforts have moved beyond genetic analysis to functional analysis of the
      molecules involved, including identification of immunodominant antigens and
      peptides as well as the role of post-translational glycosylation. Here, we focus
      on recent applications of microarray technology in understanding the detailed
      chemical biology of immune responses to disease in an effort to guide development
      of vaccines and other protective therapies.

PMID- 17500026
TI  - Exploring and designing protein function with restricted diversity.
AB  - Combinatorial libraries with restricted diversity can be used to rapidly map
      binding energetics across protein interfaces. Shotgun scanning strategies have
      been used for alanine scanning and for alternative mutagenesis schemes that
      provide high-resolution functional views of binding interfaces. In addition,
      synthetic antibodies have been derived from naive libraries restricted to a
      binary code to explore the minimal requirements for molecular recognition. These
      studies shed light on the underlying principles governing molecular recognition,
      and provide rapid yet quantitative alternatives to conventional biophysical
      methods for exploring protein structure and function.

PMID- 17500027
TI  - Micronuclei induced by airborne particulate matter from Mexico City.
AB  - Particulate air pollution is an important environmental health risk. In the
      present study, we have investigated the ability of chemically characterized water
      and organic-soluble extracts of PM(10) from two different regions of Mexico City
      to induce micronuclei in a human epithelial cell line. We also evaluated the
      association between the chemical characteristics of the PM and its genotoxicity.
      The airborne particulate samples were collected from an industrial and a
      residential region; a Hi-Vol air sampler was used to collect PM(10) on glass
      fiber filters. PM mass was determined by gravimetric analysis of the filters. One
      section of each PM(10) filter was agitated either with deionized water to extract
      water-soluble compounds or with dichloromethane to prepare organic-soluble
      compounds. The chemical composition of the extracts was determined by ion and gas
      chromatography and atomic adsorption spectroscopy. A549-human alveolar epithelial
      cells were exposed to different concentrations of PM(10) extracts and the
      cytokinesis blocked micronucleus assay was performed to measure DNA damage. Even
      though the industrial region had a higher PM concentration, higher amounts of
      metals and PAHs were found in the residential area. Both industrial and
      residential extracts induced a significant concentration-related increase in the
      micronuclei frequency. The PM(10) water-soluble industrial extract induced
      significantly more micronuclei than the one of the residential region; inversely,
      the organic residential extract induced more micronuclei than the one from the
      industrial region. The association between the induction of micronuclei and the
      chemical components obtained by the comparative analysis of standardized
      regression coefficients showed that cadmium and PAHs were significantly
      associated with micronuclei induction. Data indicate that water-soluble metals
      and the organic-soluble fraction of PM(10) are both important in the production
      of micronuclei. Effects observed, point to the risk of PM exposure and shows the
      need of integrative studies.

PMID- 17500028
TI  - Synthesis, spectral characterization and eukaryotic DNA degradation of
      thiosemicarbazones and their platinum(IV) complexes.
AB  - The condensation products of acetophenone (or its derivatives), salicylaldehyde
      and o-hydroxy-p-methoxybenzophenone with thiosemicarbazide and ethyl- or phenyl
      thiosemicarbazide are the investigated thiosemicarbazones. Their reactions with
      H(2)PtCl(6) produced Pt(IV) complexes characterized by elemental, thermal, mass,
      IR and electronic spectral studies. The coordination modes were found
      mononegative bidentate in the acetophenone derivatives and binegative tridentate
      in the salicylaldehyde derivatives. The complexes were analyzed
      thermogravimetrically and found highly stable. Some ligands and their complexes
      were screened against Sarcina sp. and E. coli using the cup-diffusion technique.
      [Pt(oHAT)(OH)Cl] shows higher activity against E. coli than the other compounds.
      The degradation power of the tested compounds on the calf thymus DNA supports
      their selectivity against bacteria and not against the human or related
      eukaryotic organisms.

PMID- 17500029
TI  - Spectroscopic properties of Dy(3+) ions in NaF-B(2)O(3)-Al(2)O(3) glasses.
AB  - This paper reports the optical properties of Dy(3+) in sodium fluoroborate
      glasses of the type XNaF.(89-X)B(2)O(3).10 Al(2)O(3).1Dy(2)O(3) (where X=8, 12,
      16, 20 and 24). Judd-Ofelt intensity parameters (Omega(2), Omega(4), Omega(6))
      are derived from the absorption spectra. The Judd-Ofelt theory has been applied
      to interpret the local environment of Dy(3+) ions and bond covalency of RE-O
      bond. These parameters have been used to calculate radiative transition
      probabilities (A(rad)), lifetimes (tau(R)) and branching ratios (beta(R)) for the
      excited level (4)F(9/2). The predicted values of tau(R) are compared with the
      measured values for (4)F(9/2) level for five glass compositions (Glass (A-E)).
      The stimulated emission cross-section sigma(lambda(P)) are also evaluated for the
      (4)F(9/2)-->(6)H(J) (J=11/2, 13/2, and 15/2) transitions.

PMID- 17500030
TI  - External quality assessment for the molecular detection of Hepatitis C virus.
AB  - BACKGROUND, OBJECTIVES AND STUDY DESIGN: External quality assessment (EQA) panels
      were distributed internationally by UK NEQAS for Microbiology to 159 participants
      for the detection, quantification and genotyping of Hepatitis C virus (HCV) in
      freeze-dried plasma from 2000 to 2004. The results were analysed to determine the
      level of standardisation of qualitative detection, quantitative detection and
      genotyping. RESULTS: The accurate detection of HCV in the panels varied from
      86.9% to 100%. Four genotypes were distributed with the panels and there was no
      significant difference in the detection of different genotypes of HCV by
      participants. Further analysis indicated most variation occurred in
      quantification of HCV at lower concentrations and from 0% to 14.8% reported
      quantitative values outside 0.5 log(10) of the median value. In addition, three
      negative specimens were distributed and false positives were found to be rare
      (0.9-2.2%) with all methods included in the study. CONCLUSION: The laboratory
      detection of HCV in plasma EQA specimens was varied, with decreasing parity of
      quantification at lower concentrations of HCV. False positives and negatives were
      rare, irrespective of the genotype under test.

PMID- 17500031
TI  - Lipid-transfer proteins in membrane trafficking at the Golgi complex.
AB  - The Golgi complex (GC) represents the central junction for membrane trafficking.
      Protein and lipid cargoes continuously move through the GC in both anterograde
      and retrograde directions, departing to and arriving from diverse destinations
      within the cell. Nevertheless, the GC is able to maintain its identity and strict
      compartmentalisation, having a different composition in terms of protein and
      lipid content compared to other organelles. The discovery of coat protein
      complexes and the elucidation of their role in sorting cargo proteins into
      specific transport carriers have provided a partial answer to this phenomenon.
      However, it is more difficult to understand how relatively small and diffusible
      molecules like lipids can be concentrated in or excluded from specific
      subcellular compartments. The discovery of lipid-transfer proteins operating in
      the secretory pathway and specifically at the GC has shed light on one possible
      way in which this lipid compartmentalisation can be accomplished. The correct
      lipid distribution along the secretory pathway is of crucial importance for cargo
      protein sorting and secretion. This review focuses on what is now known about the
      putative and effective lipid-transfer proteins at the GC, and on how they affect
      the function and structure of the GC itself.

PMID- 17500032
TI  - Functional characterization of vitamin D responding regions in the human 5
      Lipoxygenase gene.
AB  - 5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory
      leukotrienes. The 5-LO gene is a primary target of 1alpha,25-dihydroxyvitamin
      D(3) (1alpha,25(OH)(2)D(3)) and its expression is prominently increased during
      myeloid cell differentiation. Since no functional vitamin D response element
      (VDRE) has been reported for this gene so far, we performed in silico screening
      of the whole 5-LO gene area (84 kb, including 10 kb promoter region) and
      identified 22 putative VDREs. Both gelshift and reporter gene assays identified
      four of these candidates as functional VDREs. Their approximate positions are 
      2,250 (promoter), +21,400 (intron 2), +42,000 (intron 4) and +50,600 (intron 5)
      in relation to the transcription start site (TSS). Remarkably, the VDRE at
      position +42,000 is one of the strongest known VDREs of the human genome.
      Chromatin immunoprecipitation (ChIP) assays demonstrated simultaneous association
      of vitamin D receptor (VDR), retinoid X receptor (RXR) and RNA polymerase II (Pol
      II) to the 5-LO gene regions containing two of these four putative VDREs. This
      indicates DNA looping of the TSS to even very distant gene regions. In summary,
      we suggest that the upregulation of the primary 1alpha,25(OH)(2)D(3) target 5-LO
      is mediated in vivo by a prominent VDRE in intron 4.

PMID- 17500033
TI  - Pigment production in Spirulina fussiformis in different photophysical
      conditions.
AB  - The present investigation makes a comparative investigation of individual light
      source on the different commercially important pigments in Spirulina fussiformis
      in photobioreactor culture condition. Continuous culture system was carried out
      throughout the experimental condition. Initially, seed culture, corresponding to
      0.2 g/L on dry weight basis was cultivated in Zarrouks medium with different
      colored light source in reactor. Maximum daily biomass productivity, 0.8 g/L,
      0.75 g/L and 0.69 g/L in white light (WL), blue light (BL) and green light (GL),
      respectively, conditions was noticed. Pigment content during WL treatment showed
      the highest accumulation (5.5 microg/mL) of chlorophyll whereas, other pigments
      roughly remained constant without much change, implying WL intensity is better
      for chlorophyll synthesis. On the other hand, chlorophyll and phycocyanin content
      gradually increased up to 7 microg/mL and 2 mg/mL, respectively, at BL intensity.
      The response to GL was negative to all pigments studied except for phycocyanin;
      in this case a highest production (2.5 mg/mL) was seen during 18 days
      experimental period. Additionally, when yellow light (YL) treatment experiments
      were conducted, the rate of production gradually decreased from 6th day onward in
      all pigments demonstrating the photobleaching effect of YL. The average rate of
      pigments production did not show significant accumulation in red light (RL) light
      treatment except phycoerythrin which showed an increasing trend of production. It
      is worth to mention here that higher light intensity is better for production of
      phycocyanin and phycoerythrin in Spirulina.

PMID- 17500034
TI  - Sequence comparison and environmental adaptation of a bacterial endonuclease.
AB  - The periplasmic/extracellular bacterial enzyme endonuclease I was chosen as a
      model system to identify features that might be responsible for temperature- and
      salt adaptation. A statistical study of amino acid sequence properties belonging
      to endonuclease I enzymes from three mesophilic habitats (non-marine, brackish
      water and marine), and three marine temperature groups (psychrophile,
      intermediate and mesophile) has been conducted. Ten new endonuclease I genes have
      been sequenced in order to increase the sample size. A bioinformatical method of
      property dependent statistical analysis of alignments has been applied. To our
      knowledge this is the first time these methods have been used in order to
      investigate environmental adaptation of enzymes. Adaptation to low temperature
      seems to involve increased surface isoelectric point and hydrophobicity in
      contrast to salt adaptation in which the isoelectric point and hydrophobicity at
      the surface decreases. Redistribution of charge and hydrophobicity might be the
      most important signature for cold adaptation and salt adaptation of this enzyme
      class. The results indicate that general trends of adaptation are possible to
      elucidate from the amino acid sequences. Also in this paper a new scale of
      stratified B-factors, derived from the Protein Data Bank, is presented.

PMID- 17500036
TI  - ECS: an automatic enzyme classifier based on functional domain composition.
AB  - Classification for enzymes is a prerequisite for understanding their function.
      Here, an automatic enzyme identifier based on support vector machine (SVM) with
      feature vectors from protein functional domain composition was built to identify
      enzymes and further a classifier to classify enzymes into six different classes:
      oxidoreductase, transferase, hydrolase, lyase, isomerase and ligase. Jackknife
      cross-validation test was adopted to evaluate the performance of our classifier.
      The 86.03% success rate achieved for enzyme/non-enzyme identification and 91.32%
      for enzyme classification, which is much better than that of the BLAST and PSI
      BLAST based method, also outperforms several existed works. The results indicate
      that protein functional domain composition is able to capture the major features
      which facilitate the identification/classification of proteins, thus
      demonstrating that our predictor could be a more effective and promising high
      throughput method in enzyme research. Moreover, a web-based software Enzyme
      Classification System (ECS) for identification as well as classification of
      enzymes can be accessed at: http://pcal.biosino.org/.

PMID- 17500035
TI  - Simulation of conformational changes occurring when a protein interacts with its
      receptor.
AB  - In order to simulate the conformational changes occurring when a protein
      interacts with its receptor, we firstly evaluated the structural differences
      between the experimental unbound and bound conformations for selected proteins
      and created theoretical complexes by replacing, in each experimental complex, the
      protein-bound with the protein-unbound chain. The theoretical models were then
      subjected to additional modeling refinements to improve the side chain geometry.
      Comparing the theoretical and experimental complexes in term of structural and
      energetic factors is resulted that the refined theoretical complexes became more
      similar to the experimental ones. We applied the same procedure within an
      homology modeling experiment, using as templates the experimental structures of
      human interleukin-1beta (IL-1beta) unbound and bound with its receptor, to build
      models of the homologous proteins from mouse and trout in unbound and bound
      conformations and to simulate the interaction with the related receptors. Our
      results suggest that homology modeling techniques are sensitive to differences
      between bound and unbound conformations, and that modeling with accuracy the side
      chains in the complex improves the interaction and molecular recognition.
      Moreover, our refinement procedure could be used in protein-protein interaction
      studies and, also, applied in conjunction with rigid-body docking when is not
      available the protein-bound conformation.

PMID- 17500037
TI  - Optimal peeling order for pedigrees with incomplete genotypic information.
AB  - The likelihood approach is common in linkage analysis of large extended
      pedigrees. Various peeling procedures, based on the conditional independence of
      separate parts of a pedigree, are typically used for likelihood calculations. A
      peeling order may significantly affect the complexity of such calculations,
      particularly for pedigrees with loops or when many pedigrees members have unknown
      genotypes. Several algorithms have been proposed to address this problem for
      pedigrees with loops. However, the problem has not been solved for pedigrees
      without loops until now. In this paper, we suggest a new graph theoretic
      algorithm for optimal selection of peeling order in zero-loop pedigrees with
      incomplete genotypic information. It is especially useful when multiple
      likelihood calculation is needed, for example, when genetic parameters are
      estimated or linkage with multiple marker loci is tested. The algorithm can be
      easily introduced into the existing software packages for linkage analysis based
      on the Elston-Stewart algorithm for likelihood calculation. The algorithm was
      implemented in a software package PedPeel, which is freely available at
      http://mga.bionet.nsc.ru/nlru/.

PMID- 17500038
TI  - CABIN: collective analysis of biological interaction networks.
AB  - The importance of understanding biological interaction networks has fueled the
      development of numerous interaction data generation techniques, databases and
      prediction tools. However, not all prediction tools and databases predict
      interactions with one hundred percent accuracy. Generation of high-confidence
      interaction networks formulates the first step towards deciphering unknown
      protein functions, determining protein complexes and inventing drugs. The CABIN:
      Collective Analysis of Biological Interaction Networks software is an exploratory
      data analysis tool that enables analysis and integration of interactions evidence
      obtained from multiple sources, thereby increasing the confidence of
      computational predictions as well as validating experimental observations. CABIN
      has been written in Java and is available as a plugin for Cytoscape--an open
      source network visualization tool.

PMID- 17500039
TI  - Protein knots and fold complexity: some new twists.
AB  - The current knowledge on topological knots in protein structure is reviewed,
      considering in turn, knots with three, four and five strand crossings. The latter
      is the most recent to be identified and has two distinct topological forms. The
      knot observed in the protein structure is the form that requires the least number
      of strand crossings to become un-knotted. The position of the chain termini must
      also correspond to a position that allows (un) knotting in one move. This is
      postulated as a general property of protein knots and other more complex knots
      with this property are proposed as the next most likely knots that might be found
      in a protein. It is also noted that the "Jelly-roll" fold found in some all-beta
      proteins would provide likely candidates. Alternative measures of knottedness and
      entanglement are reviewed, including the occurrence of slip-knots. These measures
      are related to the complexity of the protein fold and may provide useful filters
      for selecting predicted model structures.

PMID- 17500040
TI  - Why does beta-secretase zymogen possess catalytic activity? Molecular modeling
      and molecular dynamics simulation studies.
AB  - Beta-secretase is a potential target for inhibitory drugs against Alzheimer's
      disease as it cleaves amyloid precursor protein (APP) to form insoluble amyloid
      plaques and vascular deposits in the brain. Beta-secretase is matured from its
      precursor protein, called beta-secretase zymogen, which, different from most of
      other zymogens, is also partially active in cleaving APP. Hence, it is important
      to study on the mechanism of the zymogen's activation process. This study was to
      model the 3-D structure of the zymogen, followed by intensive molecular dynamics
      (MD) simulations to identify the most probable 3-D model and to study the dynamic
      structural behavior of the zymogen for understanding the effects of pro-segment
      on the function of the enzyme. The results revealed that the dropping in
      catalytic activity of the beta-secretase zymogen could be attributed to the
      occupation of the entrance of the catalytic site of the zymogen by its pro
      segment. On the other hand, the partial catalytic activity of the zymogen could
      be explained by high fluctuation of the pro-segment in comparison with that of
      other zymogens, resulting in the occasionally exposure of the catalytic site for
      access its substrate APP. Indeed, steered MD (SMD) simulation revealed a weak
      pulling force at quasi-equilibrium state for the pro-segment of the zymogen
      leaving from the entrance, indicating that this swinging process could take place
      spontaneously. Furthermore, MM-PBSA calculation revealed a small change of free
      energy of 10.56 kal/mol between the initial and final states of the process of
      pro-segment swung outside the binding pocket of beta-secretase zymogen. These
      results not only account for the partial catalytic activity of beta-secretase
      zymogen, but also provide useful clues for discovering new potent ligands, as new
      type of drug leads for curing Alzheimer's disease, to prevent the pro-segment of
      the zymogen from leaving its catalytic site.

PMID- 17500041
TI  - Class switch recombination: a friend and a foe.
AB  - The effector functions of the antibody are determined by the heavy chain constant
      region (CH). During CSR the primarily expressed mu constant region (Cmu) of the
      heavy chain is replaced with a downstream isotype Cgamma, Calpha or Cepsilon. The
      murine immunoglobulin heavy chain (IgH) locus contains eight different CH genes.
      Class switch recombination (CSR) involves a recombination between two different
      repetitive switch (S) region sequences, located upstream of each CH gene and the
      deletion of the intervening DNA. However, this protecting mechanism is also
      involved in aberrant chromosomal translocations and generation of B cell
      malignancies. It is also involved in susceptibility to autoimmunity. The current
      review focuses on the basic mechanism of CSR and the adverse outcomes that it may
      cause.

PMID- 17500042
TI  - Enhanced susceptibility to immune nephritis in DBA/1 mice is contingent upon IL-1
      expression.
AB  - The DBA/1 mouse strain is particularly sensitive to experimental immune-mediated
      nephritis. Previous studies have indicated that various chemokines/cytokines are
      elevated in strains of mice susceptible to immune-mediated glomerulonephritis.
      One of the many elevated cytokines is IL-1. This study was designed to determine
      if IL-1 is essential for the development of immune-mediated nephritis in the
      DBA/1 mouse strain that is particularly sensitive to this disease. Both male and
      female DBA/1 mice and DBA/1.IL-1R1(-/-) mice were challenged with anti-GBM sera.
      We then compared DBA/1 mice to DBA/1.IL-1R1(-/-) mice to determine the influence
      of IL-1 on immune-mediated nephritis. Compared to DBA/1 mice, DBA/1.IL-1R1(-/-)
      mice excreted significantly less protein post anti-GBM serum challenge. None of
      the DBA/1.IL-1R1(-/-) mice, male or female, had a BUN higher than 22 mg/dl post
      challenge whereas wild-type DBA/1 mice had significantly elevated BUN. Wild-type
      DBA/1 mice exhibited pronounced glomerulonephritis, with crescent formation, as
      well as tubulo-interstitial disease compared to DBA/1.IL1R1(-/-) mice. These
      findings indicate that IL-1 is necessary for the development of nephritis in
      DBA/1 mice and suggest that the elevated IL-1 levels in these mice may be one
      reason why the DBA/1 strain is particularly sensitive to multiple end organ
      diseases.

PMID- 17500043
TI  - Effects of potential mediators of an intestinal brake mechanism on gut motility
      in Chinook salmon (Oncorhynchus tshawytscha).
AB  - Potential humoral factors controlling an intestinal brake mechanism in Chinook
      salmon were characterised in terms of their effect on frequency and amplitude of
      spontaneous contractions in gastrointestinal (GI) rings. Concentration-response
      curves of gut contractility were produced for cholecystokinin-8 (CCK-8), gastrin
      1, glucagon-like peptide-1 (GLP-1) and 5-hydroxytryptamine (5-HT) using gut rings
      from cardiac stomach (CS), pyloric stomach (PY), pyloric sphincter (Psp) and
      intestine (Int). Calculated log10 molar (M) EC50 values for CCK-8 (n=7) were: CS 
      8.15+/-0.90, PY -7.88+/-0.48, Psp -8.98+/-0.68, Int -8.93+/-0.64. Log10 M EC50
      values calculated for gastrin 1 (n=7) were: CS -12.45+/-0.66, PY -12.55+/-0.63,
      Psp -9.35+/-0.78, Int -12.69+/-1.12. Log10 M EC50 values calculated for 5-HT
      (n=6) were: CS -4.78+/-1.05 and Psp -6.18+/-1.14. GLP -1 (n=4) produced no
      response in any of the tissues examined. Spontaneous contractions, measured as
      spikes per minute and the peak force generated were also measured for each
      hormone-tissue combination. The Psp generated the greatest mass-specific force,
      with stomach rings generating the least force. Dilutions of serum from fish
      diagnosed with gastric dilation air sacculitis (GDAS +ve) increased gut
      contractility compared to controls (GDAS -ve).

PMID- 17500044
TI  - A modified fluorescent microsphere-based approach for determining resting and
      hyperemic blood flows in individual murine skeletal muscles.
AB  - The goal of this study was to develop a modified fluorescent microsphere-based
      approach for measuring resting and hyperemic blood flows in individual mouse
      skeletal muscles. Absolute resting blood flow in the left gracilis posterior was
      1.04+/-0.12 ml x min(-1).g(-1), while functional hyperemia following muscle
      activity was 5.94+/-1.33 ml x min(-1) x g(-1). Measuring absolute blood flow
      requires sampling arterial blood that serves as a flow-rate and concentration
      reference to the fluorescent microsphere (FMS) content in the tissue-of-interest
      for calculating the flow value. Because sampling arterial blood can impair
      cardiovascular function in the mouse, we also modified our FMS approach to
      determine relative blood flows in the left gracilis posterior by using the
      contralateral muscle as our reference in blood flow calculations. Absolute and
      relative hyperemia measurements detect similar increases in blood flow - 521.93+/
      216.76% and 555.24+/-213.82%, respectively. However, sampling arterial blood
      during absolute blood flow measurements significantly decreased mean arterial
      pressure from the beginning to the end of our experiments, from 102.7+/-2.18 to
      75.5+/-9.71 mm Hg. This decrease was not seen when measuring relative blood
      flows. This approach provides critical advantages over contemporary blood flow
      measurement approaches by allowing blood flow measurements in small and non
      superficial tissues.

PMID- 17500045
TI  - Alkyltransferase-like proteins.
AB  - Recent in silico analysis has revealed the presence of a group of proteins in pro
      and lower eukaryotes, but not in Man, that show extensive amino acid sequence
      similarity to known O(6)-alkylguanine-DNA alkyltransferases, but where the
      cysteine at the putative active site is replaced by another residue, usually
      tryptophan. Here we review recent work on these proteins, which we designate as
      alkyltransferase-like (ATL) proteins, and consider their mechanism of action and
      role in protecting the host organisms against the biological effects of O(6)
      alkylating agents, and their evolution. ATL proteins from Escherichia coli (eAtl,
      transcribed from the ybaz open reading frame) and Schizosaccharomyces pombe
      (Atl1) are able to bind to a range of O(6)-alkylguanine residues in DNA and to
      reversibly inhibit the action of the human alkyltransferase (MGMT) upon these
      substrates. Isolated proteins were not able to remove the methyl group in O(6)
      methylguanine-containing DNA or oligonucleotides, neither did they display
      glycosylase or endonuclease activity. S. pombe does not contain a functional
      alkyltransferase and atl1 inactivation sensitises this organism to a variety of
      alkylating agents, suggesting that Atl1 acts by binding to O(6)-alkylguanine
      lesions and signalling them for processing by other DNA repair pathways.
      Currently we cannot exclude the possibility that ATL proteins arose through
      independent mutation of the alkyltransferase gene in different organisms.
      However, analyses of the proteins from E. coli and S. pombe, are consistent with
      a common function.

PMID- 17500046
TI  - O6-methylguanine-DNA methyltransferase deficiency in developing brain:
      implications for brain tumorigenesis.
AB  - The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a
      cardinal defense against the mutagenic and carcinogenic effects of alkylating
      agents. We have reported evidence that absence of detectable MGMT activity (MGMT(
      ) phenotype) in human brain is a predisposing factor for primary brain tumors
      that affects ca. 12% of individuals [J.R. Silber, A. Blank, M.S. Bobola, B.A.
      Mueller, D.D. Kolstoe, G.A. Ojemann, M.S. Berger, Lack of the DNA repair protein
      O(6)-methylguanine-DNA methyltransferase in histologically normal brain adjacent
      to primary brain tumors, Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 6941-6946]. We
      report here that MGMT(-) phenotype in the brain of children and adults, and the
      apparent increase in risk of neurocarcinogenesis, may arise during gestation. We
      found that MGMT activity in 71 brain specimens at 6-19 weeks post-conception was
      positively correlated with gestational age (P<or=0.0015). Moreover, the
      proportion of specimens exhibiting MGMT(-) phenotype (MGMT content<0.42
      fmol/10(6)cells or 255 molecules/cell) declined progressively from 76% (16/21) at
      6-8 weeks to 13% (1/8) at 15-19 weeks. All liver specimens that accompanied MGMT(
      ) brain (15/15) had measurable MGMT activity, demonstrating that the phenotype
      was not systemic in these cases. In contrast to MGMT, apurinic endonuclease, DNA
      polymerase beta and lactate dehydrogenase activities were found in every brain
      extract assayed, and showed no significant relationship with gestational age. The
      observed gestational pattern has at least two implications for
      neurocarcinogenesis. (1) Early in development, brain tissue that has MGMT(-)
      phenotype and is rapidly proliferating may be especially vulnerable to alkylation
      induced mutations, including mutations that lead to brain tumors. (2) Persistence
      of prenatal MGMT deficiency into postnatal life in a sub-population of
      individuals may increase brain tumor risk. Our findings provide possible
      mechanistic insight into epidemiologic data associating maternal alkylating agent
      exposure with brain tumor incidence.

PMID- 17500047
TI  - Novel role of triazenes in haematological malignancies: pilot study of
      Temozolomide, Lomeguatrib and IL-2 in the chemo-immunotherapy of acute leukaemia.
AB  - Previous studies indicated that dacarbazine and Temozolomide could be highly
      effective against refractory acute leukaemia. Their activity relies mainly on the
      generation of methyl adducts at the O(6)-position of guanine in DNA. High levels
      of O(6)-methylguanine-DNA methyltransferase (MGMT) or a defective mismatch repair
      (MMR) system, are associated with cellular resistance to triazenes. The MGMT
      inhibitor, O(6)-(4-bromothenyl)guanine (Lomeguatrib), can restore in vitro
      sensitivity to Temozolomide in MMR-proficient blasts. In the early 1970s we
      discovered that, in vivo, triazene compounds induce the appearance of novel
      transplantation antigens in murine leukaemia ("Chemical Xenogenization", CX). Non
      self peptides presented by class I MHC molecules are generated by triazene
      induced somatic mutations, affecting retroviral sequences that are detectable in
      the mouse genome. Moreover, preliminary experiments suggested that human cancer
      cells can also undergo CX. Therefore, we designed a chemo-immunotherapy strategy
      in leukaemic patients as follows: (a) cytoreduction and a hypothetical CX phase,
      i.e. treatment with Lomeguatrib (to suppress MGMT activity) and Temozolomide (to
      kill sensitive blasts and to presumably induce CX in resistant leukaemic cells);
      (b) immune response recovery phase using interleukin-2 (to possibly restore an
      immune response and take advantage of the hypothetical, triazene-induced CX).
      Here we present the results of pilot study which is in progress in patients with
      refractory/relapsed acute leukaemia. In all tested cases, Lomeguatrib suppressed
      MGMT activity in vivo. Six out of eight patients showed partial or complete
      disappearance of blast cells in peripheral blood or in bone marrow. We observed
      severe and long-lasting myelosuppression, accompanied by limited non
      haematological toxicity. Up to now, two patients are alive (after 9 and 10
      months, respectively), four died of opportunistic infections and two of
      progressive disease. This investigation confirms the potential role of triazenes
      in leukaemia and highlights the contribution of Lomeguatrib in overcoming drug
      resistance. Further studies are required to establish whether Temozolomide can
      induce CX in human leukaemia, and thus offer a new approach to control minimal
      residual disease.

PMID- 17500048
TI  - Simultaneous assay of metformin and glibenclamide in human plasma based on
      extraction-less sample preparation procedure and LC/(APCI)MS.
AB  - Separation of metformin and glibenclamide was achieved within a single
      chromatographic run on a Zorbax CN column, under isocratic conditions, using
      acetonitrile and aqueous component (0.01 moles/L ammonium acetate adjusted at pH
      3.5 with acetic acid) in volumetric ratio 1/1. Plasma sample preparation is based
      on protein precipitation by means of organic solvent addition. 1,3,5-Triazine
      2,4,6-triamine (IS1) was used as internal standard for metformin, while
      gliquidone (IS2) played the same role for glibenclamide. Detection was performed
      with an ion trap mass analyzer, using atmospheric pressure chemical ionization
      (APCI). A single MS stage was used for detection of metformin and IS1, by
      extracting ion chromatograms corresponding to molecular ions. MS/MS detection in
      the SRM mode was used for glibenclamide (m/z transition from 494 to 369 Da) and
      IS2 (m/z transition from 528 to 403 Da). The method produces linear responses up
      to 2000 ng/mL for metformin and 400 ng/mL for glibenclamide, respectively. Low
      limits of quantification were found in the 40 ng/mL range for metformin and at
      the 4 ng/mL level for glibenclamide. Precision was characterized by relative
      standard deviations (RSD%) below 9%. The analytical method was successfully
      applied to a single dose, open-label, randomized, two-period, two-sequence,
      crossover bioequivalence study of two commercially available anti-diabetic
      combinations containing 400 mg metformin and 2.5 mg of glibenclamide per coated
      tablet.

PMID- 17500049
TI  - Simultaneous determination of trans-resveratrol-3-O-glucoside and its two
      metabolites in rat plasma using liquid chromatography with ultraviolet detection.
AB  - A sensitive and selective high-performance liquid chromatographic method was
      developed for simultaneous determination of trans-resveratrol-3-O-glucoside (TRG)
      and its metabolites, trans-resveratrol-3-O-glucuronide (TRN) and trans
      resveratrol (TR) in rat plasma. The plasma proteins were precipitated with
      acetonitrile and supernatant was evaporated to dryness. The analytes and internal
      standard baicalin were chromatographed on a C(18) column. The mobile phase
      consisted of 25% acetonitrile and 75% H(2)O adjusted with formic acid to pH 3.5.
      The flow-rate was 1.0 ml/min and ultraviolet detection was set at 320 nm.
      Standard curves were linear over the concentration range of 0.04-40 microg/ml for
      TRG and TRN, and 0.04-10 microg/ml for TR, respectively. The precision, expressed
      as the intra-day R.S.D. and inter-day R.S.D., was below 9.3% for TRG, TRN and TR.
      The accuracy, expressed as the relative error (RE) was within +/-7.4% for all
      analytes. The mean recoveries of TRG, TRN, TR and I.S. were 93.6%, 93.1%, 91.0%
      and 87.9%, respectively. This method was successfully applied to a
      pharmacokinetic study of TRG after an oral dose of 150 mg/kg to Wistar rats.

PMID- 17500050
TI  - Enzymatic digestion as a tool for the LC-MS/MS quantification of large peptides
      in biological matrices: measurement of chymotryptic fragments from the HIV-1
      fusion inhibitor enfuvirtide and its metabolite M-20 in human plasma.
AB  - The use of enzymatic digests of the peptide HIV-1 fusion inhibitor enfuvirtide as
      a tool for the absolute quantification of this polypeptide (MW 4492 Da) in human
      plasma by LC-MS/MS has been evaluated. Two different methods applying digestion
      of enfuvirtide with chymotrypsin after solid phase extraction (SPE) of the plasma
      samples have therefore been developed and validated. One method used a stable
      isotopically labeled analog of the complete peptide (d60-enfuvirtide) as internal
      standard (IS) and could use as much as four different chymotryptic fragments for
      the quantification of enfuvirtide in a range of 100-10,000 ng/ml. Intra- and
      inter-assay precisions and deviations from the nominal concentrations varied for
      the different fragments, but were below 9% when the four results were averaged.
      The other method used a stable isotopically labeled chymotryptic fragment of the
      peptide (d10-ASLW) as IS. Although this IS does not correct for variations in
      digestion recovery, it allows the selective quantification of enfuvirtide (100
      10,000 ng/ml), besides the quantification of the sum of enfuvirtide and its de
      amidated metabolite M-20 (120-12,000 ng/ml). Both methods were suitable for the
      absolute quantification of enfuvirtide and M-20 in plasma, but proper selection
      of the fragment(s) used for the quantification appeared crucial when the
      deuterated fragment was used as IS.

PMID- 17500051
TI  - Structure of full-length transcription regulator CcpA in the apo form.
AB  - The catabolite control protein A (CcpA) from Bacillus megaterium is a member of
      the bacterial repressor protein family GalR-LacI. CcpA functions as master
      transcriptional regulator of carbon catabolite repression/regulation in
      firmicutes. Here we present the crystal structure of full-length apo CcpA at 2.5
      A resolution from B. megaterium. The structure reveals the location of the helix
      turn-helix domain as well as the hinge region, which were not visible due to
      their high flexibility in earlier crystallographic studies on CcpA molecules. The
      structure of the apo CcpA homodimer in the present form is in contrast to other
      reported structures for CcpA.

PMID- 17500052
TI  - Hard to handle: understanding mothers' handwashing behaviour in Ghana.
AB  - While handwashing with soap (HWWS) has been identified as a major pathway to
      reducing the risk of diarrhoeal diseases, and respiratory infections, rates of
      HWWS remain low across the globe. The current study, a national survey of
      Ghanaian mothers, found that as few as 4% of mothers engaged in HWWS after
      defecation, and only 2% after cleaning a child's bottom. In a multivariate
      analysis, we explored the determinants of handwashing at these key junctures,
      with and without soap. After defecation, mother's education, knowledge of
      important times to handwash with soap, the age of her children, and a measure of
      the quality of child care were all associated with handwashing (in any form).
      However, only the latter two variables also predicted soap use amongst
      handwashers. After cleaning a child's bottom, education, knowledge of important
      times to handwash with soap, and child care quality were associated with
      handwashing (in any form), yet only one variable, a measure of disgust
      sensitivity, showed any possible relationship with soap use. While this study has
      several important limitations, failure to explain much of the observed variance,
      despite a large range of potential determinants explored, suggests that we need
      to continue complementing quantitative surveys with in-depth qualitative studies
      if we are to better understand the motivations for, and constraints to, HWWS in
      community settings.

PMID- 17500053
TI  - Cathespin H is an Fgf10 target involved in Bmp4 degradation during lung branching
      morphogenesis.
AB  - During lung development, signaling by Fgf10 (fibroblast growth factor 10) and its
      receptor Fgfr2b is critical for induction of a gene network that controls
      proliferation, differentiation, and branching of the epithelial tubules. The
      downstream events triggered by Fgf10-Fgfr2b signaling during this process are
      still poorly understood. In a global screen for transcriptional targets of Fgf10,
      we identified Ctsh (cathepsin H), a gene encoding a lysosomal cysteine protease
      of the papain family, highly up-regulated in the developing lung epithelium. Here
      we show that among other cathepsin genes present in the lung, Ctsh is the only
      family member selectively induced by Fgf10 in the lung epithelium. We provide
      evidence that, during branching morphogenesis, epithelial expression of Ctsh
      overlaps temporally and spatially with that of Bmp4 (bone morphogenetic protein
      4), another target of Fgf10. Moreover, we show that Ctsh controls the
      availability of mature Bmp4 protein in the embryonic lung and that inhibiting
      Ctsh activity leads to a marked accumulation of Bmp4 protein and disruption of
      branching morphogenesis. Tightly controlled levels of Bmp4 signaling are critical
      for patterning of the distal lung epithelium. Our study suggests a potentially
      novel posttranscriptional mechanism in which Ctsh rapidly removes Bmp4 from
      forming buds to limit Bmp4 action. The presence of both Ctsh and Bmp4 or Bmp4
      signaling activity in other developing structures, such as the kidney, yolk sac,
      and choroid plexus, suggests a possible general role of Ctsh in regulating Bmp4
      proteolysis in different morphogenetic events.

PMID- 17500054
TI  - Differentially spliced isoforms of FAT1 are asymmetrically distributed within
      migrating cells.
AB  - Cadherin FAT1 is localized along the leading edge of mammalian cells and is
      necessary for polarization and directed migration. It is essential for
      maintenance of the complex cytoarchitecture of the glomerular filtration barrier
      within the kidney. In this study, three novel splice isoforms of FAT1 with
      important functional differences in comparison with wild-type FAT1, FAT1(WT),
      were identified. The novel variants contained additional short peptide sequences
      at a specific site of the cytoplasmic domain (+12 or +32 or +8 amino acids, the
      latter resulting in a premature stop codon). FAT1(+12) was expressed in all
      peripheral tissues together with FAT1(WT), whereas FAT1(+32) and -(+8TR) were
      brain-specific. At the subcellular level, exclusively FAT1(WT) was localized
      along the cellular leading edge, whereas spliced FAT1 isoforms were confined to
      intercellular junctions. A shift of FAT1(WT) expression toward a predominance of
      FAT1(+12) was observed in migratory versus quiescent cells. A similar shift was
      observed in vivo when glomeruli from healthy individuals were compared with those
      from patients affected by glomerulonephritis. At the molecular level, the
      differential subcellular localization of FAT1 isoforms was mediated by a novel
      region harboring a phosphotyrosine-binding-like motif (DN_XYH), which was
      disrupted by the peptide inserts in the alternative splice variants.
      Overexpression of FAT1(WT) or specific knockdown of spliced FAT1 isoforms
      resulted in formation of cellular protrusions or increased wound healing,
      respectively. In summary, FAT1(WT) is the only FAT1 isoform located along the
      cellular leading edge. Only FAT1(WT) is up-regulated in migration, induces
      cellular process formation when overexpressed, and is necessary for efficient
      wound healing.

PMID- 17500055
TI  - Activation of p61Hck triggers WASp- and Arp2/3-dependent actin-comet tail
      biogenesis and accelerates lysosomes.
AB  - Secretory lysosomes exist in few cell types, but various mechanisms are involved
      to ensure their mobilization within the cytoplasm. In phagocytes, lysosome
      exocytosis is a regulated phenomenon at least in part under the control of the
      phagocyte-specific and lysosome-associated Src-kinase p61Hck (hematopoietic cell
      kinase). We show here that p61Hck activation triggered polymerization of actin at
      the membrane of lysosomes, which resulted in F-actin structures similar to comet
      tails observed on endocytic vesicles. We correlated this actin-comet biogenesis
      to a 35% acceleration of p61Hck-lysosomes in cells, which was dependent on actin
      polymerization and required an intact microtubular network. It was possible to
      initiate the formation of actin tails on p61Hck-positive lysosomes and on p61Hck
      associated latex beads incubated in human phagocyte cytosolic extracts. The in
      vitro reconstitution on beads indicated that other lysosomal proteins were
      dispensable in this mechanism. The de novo actin polymerization process was
      functionally dependent on the kinase activity of Hck, WASp, the Arp2/3 complex,
      and Cdc42 but not Rac or Rho. Thus, we identified p61Hck as the first lysosomal
      protein able to recruit the molecular machinery responsible for actin tail
      formation. Altogether, our results suggest a new mechanism for lysosome motility
      involving p61Hck, actin-comet tail biogenesis, and the microtubule network.

PMID- 17500056
TI  - Organelle targeting of myosin XI is mediated by two globular tail subdomains with
      separate cargo binding sites.
AB  - Myosin XI are actin-based molecular motors that are thought to drive organelle
      movements in plants, analogous to myosin V in animals and fungi. Similar domain
      structure of these myosins suggests that binding to organelles may occur via the
      globular tail domain in both types of motors, even though sequence similarity is
      low. To address this hypothesis, we developed a structure homology model for the
      globular tail of MYA1, a myosin XI from Arabidopsis, based on the known structure
      of yeast myosin V (Myo2p) globular tail. This model suggested an interaction
      between two subdomains of the globular tail which was verified by yeast two
      hybrid assay and by in vivo bimolecular fluorescence complementation (BiFC).
      Interface mapping demonstrated that this subdomain interaction depends critically
      on the C terminus of helix H6 as well as three specific residues in helices H3
      and H15, consistent with the structural prediction. The reconstituted globular
      tails of several Arabidopsis myosin XIs in BiFC assays targeted to peroxisomes in
      plant cells, identifying this domain as sufficient for cargo binding. Unlike
      myosin V, either subdomain of myosin XI alone was targeting-competent and
      responsible for association with different organelles. In addition, our data
      suggest that organelle binding is regulated by an allosteric interaction between
      two tail subdomains. We conclude that the globular tail of myosin XI shares a
      similar structure with that of myosin V, but has evolved plant-specific cargo
      binding mechanisms.

PMID- 17500057
TI  - Leukocyte antigen-related deficiency enhances insulin-like growth factor-1
      signaling in vascular smooth muscle cells and promotes neointima formation in
      response to vascular injury.
AB  - Increase in the expression of leukocyte antigen-related (LAR) protein causes
      insulin resistance, an important contributor to atherosclerosis. However, the
      function of LAR in atherosclerosis is not known. To address whether LAR is
      important in the response of vascular cells to atherogenic stimuli, we
      investigated cell proliferation, migration, and insulin-like growth factor-1
      receptor (IGF-1R) signaling in wild-type and LAR(-/-) mouse vascular smooth
      muscle cells (VSMC) treated with IGF-1. Absence of LAR significantly enhanced
      proliferation and migration of VSMC compared with wild-type cells after IGF-1
      treatment. U0126 and LY249002, specific inhibitors of MAPK/ERK kinase (MEK) and
      phosphoinositide 3-kinase, respectively, inhibited IGF-1-induced DNA synthesis
      and migration in both wild-type and LAR(-/-) VSMC. IGF-1 markedly enhanced IGF-1R
      phosphorylation in both wild-type and LAR(-/-) VSMC, but the phosphorylation was
      90% higher in knock-out cells compared with wild-type cells. Absence of LAR
      enhanced phosphorylation of insulin receptor substrate-1 and insulin receptor
      substrate-1-associated phosphoinositide 3-kinase activity in VSMC treated with
      IGF-1. IGF-1-induced phosphorylation of ERK1/2 also increased significantly in
      LAR(-/-) VSMC compared with wild-type cells. Furthermore, LAR directly binds to
      IGF-1R in glutathione S-transferase-LAR pull-down and IGF-1R immunoprecipitation
      experiments and recombinant LAR dephosphorylates IGF-1R in vitro. Neointima
      formation in response to arterial injury and IGF-1R phosphorylation in neointima
      increased significantly in LAR(-/-) mice compared with wild-type mice. A
      significant decrease in body weight, fasting insulin, and IGF-1 levels were
      observed in LAR(-/-) mice compared with wild-type mice. Together, these data
      indicate that LAR regulates IGF-1R signaling in VSMC and dysregulation of this
      phosphatase may lead to VSMC hyperplasia.

PMID- 17500058
TI  - The ubiquitin ligase SCF(betaTrCP) regulates the degradation of the growth
      hormone receptor.
AB  - SCF ubiquitin ligases play a pivotal role in the regulation of cell division and
      various signal transduction pathways, which in turn are involved in cell growth,
      survival, and transformation. SCF(TrCP) recognizes the double phosphorylated
      DSGPhiXS destruction motif in beta-catenin and IkappaB. We show that the same
      ligase drives endocytosis and degradation of the growth hormone receptor (GHR) in
      a ligand-independent fashion. The F-box protein beta-TrCP binds directly and
      specifically with its WD40 domain to a novel recognition motif, previously
      designated as the ubiquitin-dependent endocytosis motif. Receptor degradation
      requires an active neddylation system, implicating ubiquitin ligase activity. GHR
      TrCP binding, but not GHR ubiquitination, is necessary for endocytosis. TrCP2
      silencing is more effective on GHR degradation and endocytosis than TrCP1,
      although overexpression of either isoform restores TrCP function in silenced
      cells. Together, these findings provide direct evidence for a key role of the
      SCF(TrCP) in the endocytosis and degradation of an important factor in growth,
      immunity, and life span regulation.

PMID- 17500059
TI  - Functions of chondroitin sulfate/dermatan sulfate chains in brain development.
      Critical roles of E and iE disaccharide units recognized by a single chain
      antibody GD3G7.
AB  - Chondroitin sulfate (CS) and dermatan sulfate (DS) have been implicated in the
      processes of neural development in the brain. In this study, we characterized
      developmentally regulated brain CS/DS chains using a single chain antibody,
      GD3G7, produced by the phage display technique. Evaluation of the specificity of
      GD3G7 toward various glycosaminoglycan preparations showed that this antibody
      specifically reacted with squid CS-E (rich in the GlcUAbeta1-3GalNAc(4,6-O
      sulfate) disaccharide unit E), hagfish CS-H (rich in the IdoUAalpha1-3GalNAc(4,6
      O-sulfate) unit iE), and shark skin DS (rich in both E and iE units). In situ
      hybridization for the expression of N-acetylgalac-tosamine-4-sulfate 6-O
      sulfotransferase in the postnatal mouse brain, which is involved in the
      biosynthesis of CS/DS-E, showed a widespread expression of the transcript in the
      developing brain except at postnatal day 7, where strong expression was observed
      in the external granule cell layer in the cerebellum. The expression switched
      from the external to internal granule cell layer with development.
      Immunohistochemical localization of GD3G7 in the mouse brain showed that the
      epitope was relatively abundant in the cerebellum, hippocampus, and olfactory
      bulb. GD3G7 suppressed the growth of neurites in embryonic hippocampal neurons
      mediated by CS-E, suggesting that the epitope is embedded in the neurite
      outgrowth-promoting motif of CS-E. In addition, a CS-E decasaccharide fraction
      was found to be the critical minimal structure needed for recognition by GD3G7.
      Four discrete decasaccharide epitopic sequences were identified. The antibody
      GD3G7 has broad applications in investigations of CS/DS chains during the central
      nervous system's development and under various pathological conditions.

PMID- 17500060
TI  - Nephroblastoma overexpressed (Nov) inhibits osteoblastogenesis and causes
      osteopenia.
AB  - Nephroblastoma overexpressed (Nov), a member of the Cyr 61, connective tissue
      growth factor, Nov (CCN) family of proteins, is expressed by osteoblasts, but its
      function in cells of the osteoblastic lineage is not known. We investigated the
      effects of Nov overexpression by transducing murine ST-2 stromal and MC3T3
      osteoblastic cells with a retroviral vector where Nov is under the control of the
      cytomegalovirus promoter. We also examined the skeletal phenotype of transgenic
      mice expressing Nov under the control of the human osteocalcin promoter.
      Overexpression of Nov in ST-2 cells inhibited the appearance of mineralized
      nodules and decreased alkaline phosphatase activity and osteocalcin mRNA levels.
      Nov overexpression inhibited the effect of bone morphogenetic protein (BMP)-2 on
      the phosphorylation of Smad 1/5/8; on the transactivation of 12xSBE-Oc-pGL3, a
      BMP/Smad signaling reporter construct, and of Wnt 3 on cytoplasmic beta-catenin
      levels; and on the transactivation of the Wnt/beta-catenin signaling reporter
      construct 16xTCF-Luc. Nov overexpression did not activate Notch or transforming
      growth factor beta signaling. Glutathione S-transferase pulldown assays
      demonstrated direct Nov-BMP interactions. Nov transgenic mice exhibited
      osteopenia. In conclusion, Nov binds BMP-2 and antagonizes BMP-2 and Wnt
      activity, and its overexpression inhibits osteoblastogenesis and causes
      osteopenia.

PMID- 17500061
TI  - Nuclear import of the MUC1-C oncoprotein is mediated by nucleoporin Nup62.
AB  - The MUC1 heterodimeric transmembrane protein is aberrantly overexpressed by most
      human carcinomas. The MUC1 C-terminal subunit (MUC1-C) is devoid of a classical
      nuclear localization signal and is targeted to the nucleus by an unknown
      mechanism. The present results demonstrate that MUC1-C associates with importin
      beta and not importin alpha. The results also show that, like importin beta, MUC1
      C binds to Nup62 (nucleoporin p62). MUC1-C binds directly to the Nup62 central
      domain and indirectly to the Nup62 C-terminal alpha-helical coiled-coil domain.
      We demonstrate that MUC1-C forms oligomers and that oligomerization is necessary
      for binding to Nup62. The MUC1-C cytoplasmic domain contains a CQC motif that
      when mutated to AQA abrogates oligomerization and binding to Nup62. Stable
      expression of MUC1 with the CQC --> AQA mutations was associated with targeting
      to the cell membrane and cytosol and attenuation of nuclear localization. The
      results further show that expression of MUC1(CQC-AQA) attenuates MUC1-induced (i)
      transcriptional coactivation, (ii) anchorage-independent growth, and (iii)
      tumorigenicity. These findings indicate that the MUC1-C oncoprotein is imported
      to the nucleus by a pathway involving Nup62.

PMID- 17500062
TI  - Cell type-specific post-translational modifications of mouse osteopontin are
      associated with different adhesive properties.
AB  - Osteopontin (OPN) is a highly modified integrin-binding protein found in all body
      fluids. Expression of OPN is strongly correlated with poor prognosis in many
      different human cancers, suggesting an important but poorly understood role for
      this protein in tumorigenesis and metastasis. The protein exists in a number of
      different isoforms differing in the degree of post-translational modifications
      that are likely to exhibit different functional properties. This study examines
      for the first time the post-translational modifications of OPN from transformed
      cells and the effects of these modifications on cell biology. We have
      characterized the complete phosphorylation and glycosylation patterns of OPN
      expressed by murine ras-transformed fibroblasts (FbOPN) and differentiating
      osteoblasts (ObOPN) by a combination of mass spectrometric analyses and Edman
      degradation. Mass spectrometric analysis showed masses of 34.9 and 35.9 kDa for
      FbOPN and ObOPN, respectively. Enzymatic dephosphorylation, sequence, and mass
      analyses demonstrated that FbOPN contains approximately four phosphate groups
      distributed over 16 potential phosphorylation sites, whereas ObOPN contains
      approximately 21 phosphate groups distributed over 27 sites. Five residues are O
      glycosylated in both isoforms. These residues are fully modified in FbOPN,
      whereas one site is partially glycosylated in ObOPN. Although both forms of OPN
      mediated robust integrin-mediated adhesion of mouse ras-transformed fibroblasts,
      the less phosphorylated FbOPN mediated binding of MDA-MD-435 human tumor cells
      almost 6-fold more than the heavy phosphorylated ObOPN. These results strongly
      support the hypothesis that the degree of phosphorylation of OPN produced by
      different cell types can regulate its function.

PMID- 17500063
TI  - Characterization of the amino acids involved in substrate specificity of
      methionine sulfoxide reductase A.
AB  - Methionine sulfoxide reductases (Msrs) are ubiquitous enzymes that catalyze the
      thioredoxin-dependent reduction of methionine sulfoxide (MetSO) back to
      methionine. In vivo, Msrs are essential in protecting cells against oxidative
      damages on proteins and in the virulence of some bacteria. There exists two
      structurally unrelated classes of Msrs. MsrAs are stereo-specific toward the S
      epimer on the sulfur of the sulfoxide, whereas MsrBs are specific toward the R
      isomer. Both classes of Msrs display a similar catalytic mechanism of sulfoxide
      reduction by thiols via the sulfenic acid chemistry and a better affinity for
      protein-bound MetSO than for free MetSO. Recently, the role of the amino acids
      implicated in the catalysis of the reductase step of Neisseria meningitidis MsrA
      was determined. In the present study, the invariant amino acids potentially
      involved in substrate binding, i.e. Phe-52, Trp-53, Asp-129, His-186, Tyr-189,
      and Tyr-197, were substituted. The catalytic parameters under steady-state
      conditions and of the reductase step of the mutated MsrAs were determined and
      compared with those of the wild type. Altogether, the results support the
      presence of at least two binding subsites. The first one, whose contribution is
      major in the efficiency of the reductase step and in which the epsilon-methyl
      group of MetSO binds, is the hydrophobic pocket formed by Phe-52 and Trp-53, the
      position of the indole ring being stabilized by interactions with His-186 and Tyr
      189. The second subsite composed of Asp-129 and Tyr-197 contributes to the
      binding of the main chain of the substrate but to a lesser extent.

PMID- 17500064
TI  - Role of AMP kinase and PPARdelta in the regulation of lipid and glucose
      metabolism in human skeletal muscle.
AB  - The peroxisome proliferator-activated receptor (PPAR)delta has been implicated in
      the regulation of lipid metabolism in skeletal muscle. Furthermore, activation of
      PPARdelta has been proposed to improve insulin sensitivity and reduce glucose
      levels in animal models of type 2 diabetes. We recently demonstrated that the
      PPARdelta agonist GW501516 activates AMP-activated protein kinase (AMPK) and
      stimulates glucose uptake in skeletal muscle. However, the underlying mechanism
      remains to be clearly identified. In this study, we first confirmed that
      incubation of primary cultured human muscle cells with GW501516 induced AMPK
      phosphorylation and increased fatty acid transport and oxidation and glucose
      uptake. Using small interfering RNA, we have demonstrated that PPARdelta
      expression is required for the effect of GW501516 on the intracellular
      accumulation of fatty acids. Furthermore, we have shown that the subsequent
      increase in fatty acid oxidation induced by GW501516 is dependent on both
      PPARdelta and AMPK. Concomitant with these metabolic changes, we provide evidence
      that GW501516 increases the expression of key genes involved in lipid metabolism
      (FABP3, CPT1, and PDK4) by a PPARdelta-dependent mechanism. Finally, we have also
      demonstrated that the GW501516-mediated increase in glucose uptake requires AMPK
      but not PPARdelta. In conclusion, the PPARdelta agonist GW501516 promotes changes
      in lipid/glucose metabolism and gene expression in human skeletal muscle cells by
      PPARdelta- and AMPK-dependent and -independent mechanisms.

PMID- 17500066
TI  - Beta-arrestin-dependent regulation of the cofilin pathway downstream of protease
      activated receptor-2.
AB  - Beta-arrestins are pleiotropic molecules that mediate signal desensitization, G
      protein-independent signaling, scaffolding of signaling molecules, and
      chemotaxis. Protease-activated receptor-2 (PAR-2), a Galpha(q/11)-coupled
      receptor, which has been proposed as a therapeutic target for inflammation and
      cancer, requires the scaffolding function of beta-arrestins for chemotaxis. We
      hypothesized that PAR-2 can trigger specific responses by differential activation
      of two pathways, one through classic Galpha(q)/Ca(2+) signaling and one through
      beta-arrestins, and we proposed that the latter involves scaffolding of proteins
      involved in cell migration and actin assembly. Here we demonstrate the following.
      (a) PAR-2 promotes beta-arrestin-dependent dephosphorylation and activation of
      the actin filament-severing protein (cofilin) independently of Galpha(q)/Ca(2+)
      signaling. (b) PAR-2-evoked cofilin dephosphorylation requires both the activity
      of a recently identified cofilin-specific phosphatase (chronophin) and inhibition
      of LIM kinase (LIMK) activity. (c) Beta-arrestins can interact with cofilin,
      LIMK, and chronophin and colocalize with them in membrane protrusions, suggesting
      that beta-arrestins may spatially regulate their activities. These findings
      identify cofilin as a novel target of beta-arrestin-dependent scaffolding and
      suggest that many PAR-2-induced processes may be independent of Galpha(q/11)
      protein coupling.

PMID- 17500065
TI  - PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4
      methyltransferase complex.
AB  - PTIP, a protein with tandem BRCT domains, has been implicated in DNA damage
      response. However, its normal cellular functions remain unclear. Here we show
      that while ectopically expressed PTIP is capable of interacting with DNA damage
      response proteins including 53BP1, endogenous PTIP, and a novel protein PA1 are
      both components of a Set1-like histone methyltransferase (HMT) complex that also
      contains ASH2L, RBBP5, WDR5, hDPY-30, NCOA6, SET domain-containing HMTs MLL3 and
      MLL4, and substoichiometric amount of JmjC domain-containing putative histone
      demethylase UTX. PTIP complex carries robust HMT activity and specifically
      methylates lysine 4 (K4) on histone H3. Furthermore, PA1 binds PTIP directly and
      requires PTIP for interaction with the rest of the complex. Moreover, we show
      that hDPY-30 binds ASH2L directly. The evolutionarily conserved hDPY-30, ASH2L,
      RBBP5, and WDR5 likely constitute a subcomplex that is shared by all human Set1
      like HMT complexes. In contrast, PTIP, PA1, and UTX specifically associate with
      the PTIP complex. Thus, in cells without DNA damage agent treatment, the
      endogenous PTIP associates with a Set1-like HMT complex of unique subunit
      composition. As histone H3 K4 methylation associates with active genes, our study
      suggests a potential role of PTIP in the regulation of gene expression.

PMID- 17500067
TI  - Mechanistic studies of MDM2-mediated ubiquitination in p53 regulation.
AB  - As a central regulator for cell cycle arrest, apoptosis, and cellular senescence,
      p53 requires multiple layers of regulatory control to ensure correct temporal and
      spatial functions. It is well accepted that Mdm2-mediated ubiquitination plays a
      crucial role in p53 regulation. In addition to proteasome-mediated degradation,
      ubiquitination of p53 by Mdm2 acts a key signal for its nuclear export. Nuclear
      export has previously been thought to require the disassociation of the p53
      tetramer and exposure of the intrinsic nuclear export signal. To elucidate the
      molecular mechanism of degradation-independent repression on p53 by Mdm2, we have
      developed a two-step approach to purify ubiquitinated forms of p53 induced by
      Mdm2 from human cells. Surprisingly, however, we found that ubiquitination has no
      effect on the tetramerization/oligomerization of p53, arguing against this
      seemingly well accepted model. Moreover, nuclear export of p53 alone is not
      sufficient to completely abolish p53 activity. Ubiquitination-mediated repression
      of p53 by Mdm2 acts at least, in part, through inhibiting the sequence-specific
      DNA binding activity. Thus, our results have important implications regarding the
      mechanisms by which Mdm2 acts on p53.

PMID- 17500068
TI  - Tumor necrosis factor alpha (TNFalpha) stimulates Map4k4 expression through
      TNFalpha receptor 1 signaling to c-Jun and activating transcription factor 2.
AB  - Tumor necrosis factor alpha (TNFalpha) is a cytokine secreted by macrophages and
      adipocytes that contributes to the low grade inflammation and insulin resistance
      observed in obesity. TNFalpha signaling decreases peroxisome proliferator
      activated receptor gamma and glucose transporter isoform 4 (GLUT4) expression in
      adipocytes, impairing insulin action, and this is mediated in part by the yeast
      Ste20 protein kinase ortholog Map4k4. Here we show that Map4k4 expression is
      selectively up-regulated by TNFalpha, whereas the expression of the protein
      kinases JNK1/2, ERK1/2, p38 stress-activated protein kinase, and mitogen
      activated protein kinase kinases 4/7 shows little or no response. Furthermore,
      the cytokines interleukin 1beta (IL-1beta) and IL-6 as well as lipopolysaccharide
      fail to increase Map4k4 mRNA levels in cultured adipocytes under conditions where
      TNFalpha elicits a 3-fold effect. Using agonistic and antagonistic antibodies and
      small interfering RNA (siRNA) against TNFalpha receptor 1 (TNFR1) and TNFalpha
      receptor 2 (TNFR2), we show that TNFR1, but not TNFR2, mediates the increase in
      Map4k4 expression. TNFR1, but not TNFR2, also mediates a potent effect of
      TNFalpha on the phosphorylation of JNK1/2 and p38 stress-activated protein kinase
      and their downstream transcription factor substrates c-Jun and activating
      transcription factor 2 (ATF2). siRNA-based depletion of c-Jun and ATF2 attenuated
      TNFalpha action on Map4k4 mRNA expression. Consistent with this concept, the
      phosphorylation of ATF2 along with the expression and phosphorylation of c-Jun by
      TNFalpha signaling was more robust and prolonged compared with that of IL-1beta,
      which failed to modulate Map4k4. These data reveal that TNFalpha selectively
      stimulates the expression of a key component of its own signaling pathway,
      Map4k4, through a TNFR1-dependent mechanism that targets the transcription
      factors c-Jun and ATF2.

PMID- 17500069
TI  - Golgi-associated maturation of very low density lipoproteins involves
      conformational changes in apolipoprotein B, but is not dependent on
      apolipoprotein E.
AB  - The major protein component in secreted very low density lipoproteins (VLDL) is
      apoB, and it is established that these particles can reach sizes approaching 100
      nm. We previously employed a cell-free system to investigate the nature of the
      vesicles in which this large cargo exits the endoplasmic reticulum (ER)
      (Gusarova, V., Brodsky, J. L., and Fisher, E. A. (2003) J. Biol. Chem. 278, 48051
      48058). We found that apoB-containing lipoproteins exit the ER as dense lipid
      protein complexes regardless of the final sizes of the particles and that further
      expansion occurs via post-ER lipidation. Here, we focused on maturation in the
      Golgi apparatus. In three separate approaches, we found that VLDL maturation (as
      assessed by changes in buoyant density) was associated with conformational
      changes in apoB. In addition, as the size of VLDL expanded, apoE concentrated in
      a subclass of Golgi microsomes or Golgi-derived vesicles that co-migrated with
      apoB-containing microsomes or vesicles, respectively. A relationship between apoB
      and apoE was further confirmed in co-localization studies by immunoelectron
      microscopy. These combined results are consistent with previous suggestions that
      apoE is required for VLDL maturation. To our surprise, however, we observed
      robust secretion of mature VLDL when apoE synthesis was inhibited in either rat
      hepatoma cells or apoE(-/-) mouse primary hepatocytes. We conclude that VLDL
      maturation in the Golgi involves apoB conformational changes and that the
      expansion of the lipoprotein does not require apoE; rather, the increase in VLDL
      surface area favors apoE binding.

PMID- 17500070
TI  - Constitutively active parathyroid hormone receptor signaling in cells in
      osteoblastic lineage suppresses mechanical unloading-induced bone resorption.
AB  - Multiple signaling pathways participate in the regulation of bone remodeling, and
      pathological negative balance in the regulation results in osteoporosis. However,
      interactions of signaling pathways that act comprehensively in concert to
      maintain bone mass are not fully understood. We investigated roles of parathyroid
      hormone receptor (PTH/PTHrP receptor) signaling in osteoblasts in unloading
      induced bone loss using transgenic mice. Hind limb unloading by tail suspension
      reduced bone mass in wild-type mice. In contrast, signaling by constitutively
      active PTH/PTHrP receptor (caPPR), whose expression was regulated by the
      osteoblast-specific Col1a1 promoter (Col1a1-caPPR), suppressed unloading-induced
      reduction in bone mass in these transgenic mice. In Col1a1-caPPR transgenic (Tg)
      mice, hind limb unloading suppressed bone formation parameters in vivo and
      mineralized nodule formation in vitro similarly to those observed in wild-type
      mice. In addition, serum osteocalcin levels and mRNA expression levels of type I
      collagen, Runx2 and Osterix in bone were suppressed by unloading in both wild
      type mice and Tg mice. However, in contrast to unloading-induced enhancement of
      bone resorption parameters in wild-type mice, Col1a1-caPPR signaling suppressed,
      rather than enhanced, osteoclast number and osteoclast surface as well as urinary
      deoxypyridinoline excretion upon unloading. Col1a1-caPPR signaling also
      suppressed mRNA expression levels of RANK and c-fms in bone upon unloading.
      Although the M-CSF and monocyte chemoattractant protein 1 (MCP-1) mRNA levels
      were enhanced in control Tg mice, these levels were suppressed in unloaded Tg
      mice. These results indicated that constitutive activation of PTH/PTHrP receptor
      signaling in osteoblastic cells suppresses unloading-induced bone loss
      specifically through the regulation of osteoclastic activity.

PMID- 17500071
TI  - Regulation of secreted Frizzled-related protein-1 by heparin.
AB  - Secreted Frizzled-related protein-1 (sFRP-1) belongs to a class of extracellular
      antagonists that modulate Wnt signaling pathways by preventing ligand-receptor
      interactions among Wnts and Frizzled membrane receptor complexes. sFRP-1 and Wnts
      are heparin-binding proteins, and their interaction can be stabilized by heparin
      in vitro. Here we report that heparin can specifically enhance recombinant sFRP-1
      accumulation in a cell type-specific manner. The effect requires O-sulfation in
      heparin, and involves fibroblast growth factor-2 as well as fibroblast growth
      factor receptor-1. Interestingly, further investigation uncovers that heparin can
      also affect the post-translational modification of sFRP-1. We demonstrate that
      sFRP-1 is post-translationally modified by tyrosine sulfation at tyrosines 34 and
      36, which is inhibited by the treatment of heparin. The results suggest that
      accumulation of sFRP-1 induced by heparin is in part due to the relative
      stabilization of unsulfated sFRP-1 and the direct stabilization by heparin. The
      study has revealed a multifaceted regulation on sFRP-1 protein by heparin.

PMID- 17500072
TI  - Patellofemoral joint osteoarthritis: an important subgroup of knee
      osteoarthritis.
AB  - Knee osteoarthritis (OA) is a prevalent disease afflicting elderly people. As the
      knee joint is tri-compartmental, numerous radiographic patterns of disease are
      possible. The patellofemoral joint (PFJ) is one of the most commonly affected
      compartments. Although PFJ OA is frequently observed, this particular disease sub
      group has gone largely unrecognised. Recent research suggests that not only is
      the PFJ an important source of symptoms in knee OA, but also that afflicted
      individuals demonstrate disease features distinct from those observed in
      tibiofemoral joint OA. This has implications for the assessment and treatment of
      patients with PFJ OA. This review summarises the evidence suggesting why PFJ OA
      should be considered a distinct clinical entity and how it may best be managed
      using conservative, non-pharmacological treatment approaches that are targeted to
      the PFJ. Interventions such as patella taping, patella bracing and physiotherapy
      have the potential to alleviate joint stress and symptoms for people with this
      condition.

PMID- 17500073
TI  - Fifty years of anti-ds DNA antibodies: are we approaching journey's end?
AB  - The year 2007 marks the 50th anniversary of the identification of antibodies to
      double-stranded (ds) DNA. Whilst widely regarded as synonymous with patients who
      have systemic lupus erythematosus (SLE), doubts have been raised about their
      significance and the extent to which they are genuinely part of the pathogenesis
      of the disease rather than being mere bystanders. Problems with assays used to
      detect them are still evident but they remain widely utilized both to help
      establish the diagnosis of SLE and to monitor the progress of the disease. This
      review explores each of these aspects and concludes that whilst some way short of
      ideal, their measurement remains a useful criterion for the disease and some of
      these antibodies do appear to be genuinely pathogenic. However, further research
      is needed to establish beyond 'reasonable doubt' whether they are merely part of
      the spectrum of anti-nucleosome antibodies, the precise mechanisms by which they
      'exert' their pathogenic effects and to what extent blocking them would be a
      useful therapeutic goal.

PMID- 17500074
TI  - Bisphosphonates and osteonecrosis of the jaw.

PMID- 17500075
TI  - Prevalence and risk factors of osteoporosis in female SLE patients-extended
      report.
AB  - OBJECTIVES: To determine the frequency of osteoporosis and possible risk factors
      of low bone mineral density (BMD) in women with systemic lupus erythematous (SLE)
      in western Sweden. In addition, to evaluate if adequate anti-osteoporotic
      treatment was provided. METHODS: BMD was measured at radius, lumbar spine and hip
      by dual X-ray absorptiometry (DXA). An 'expected' control BMD was calculated for
      each patient. Simple and multiple linear regression analyses were performed to
      determine associations between BMD and demographic and disease-related variables.
      RESULTS: One hundred and sixty-three women were included. Median age was 47 (20
      82) yrs, 89 (55%) were post-menopausal and 85 (52%) were taking
      glucocorticosteroids. BMD was significantly reduced in all measured sites
      compared with expected BMD. Thirty-seven (23%), 18 (11%) and 6 (4%) of the
      patients were osteoporotic in at least one, two and three or more measured
      locations. Bisphosphonates were used by 23 (27%) of patients taking
      glucocorticosteroids and 13 (35%) with osteoporosis. High age and low weight or
      BMI were associated with low BMD in all measured sites. In total hip, high
      SLICC/American Collage of Rheumatology (ACR), ESR and 'combinations of DMARD'
      were additional markers of low BMD. High S-creatinine was associated with low BMD
      in lumbal spine whereas high S-creatinine and CRP were markers in radius.
      CONCLUSION: Women with SLE are at greater risk of osteoporosis compared with
      controls and few are treated adequately. Factors associated with low BMD in SLE
      are high age and low weight but also markers of inflammation, impaired kidney
      function and disease damage, however glucocorticosteroids were not associated.

PMID- 17500076
TI  - Musculoskeletal abnormalities in juvenile idiopathic arthritis--a 4-year
      longitudinal study.
AB  - OBJECTIVES: Bone density in juvenile idiopathic arthritis (JIA) is largely normal
      whereas geometric parameters of bone are abnormal. The most prominent changes are
      a reduction in muscle cross sectional area (CSA) and muscle force. The aim of
      this study was to assess the evolution of these changes throughout the course of
      the disease. METHODS: Twenty-five JIA patients were assessed by peripheral
      quantitative computed tomography longitudinally with a median of 48 months
      between measurements. At the non-dominant forearm, parameters of bone density and
      geometry as well as muscle CSA were recorded. The strength-strain index (SSI) as
      an indicator of bone strength was determined. RESULTS: Muscle CSA improved from a
      median Z-score of -1.94 to -1.10 at follow-up. Cortical thickness increased from 
      1.55 to -0.97 whereas marrow area remained enlarged at 0.96 vs 1.05. Cortical
      density remained normal at 0.34 vs 0.69 and trabecular density improved from 
      0.75 to -0.36. The SSI increased from -0.79 to -0.13. CONCLUSIONS: JIA patients
      show some improvement in muscle CSA and an increase in cortical thickness. The
      marrow area remains enlarged but by increasing the cortical thickness, area and
      diameter, bone strength increases. These geometric adaptations, for the first
      time shown in this study, nevertheless represent a disturbance in skeletal
      development. In addition to efficient disease control, training modalities to
      improve muscle strength and subsequent bone development have to be included in
      therapeutic approaches.

PMID- 17500078
TI  - Provisional guidelines for applying the Department of Health (England) 18-week
      patient pathway to specialist rheumatology care.
AB  - OBJECTIVES: The Government Department of Health (England) has set a target that
      by 2008 patients on pathways that do or may involve medical or surgical
      consultant-led care should wait no longer than 18 weeks from referral to start of
      definitive treatment. Department of Health guidance must be interpreted and
      applied to patients with rheumatological problems. METHODS: Provisional
      guidelines have been prepared in collaboration between the British Society for
      Rheumatology, British Pain Society, Department of Health (England) and other key
      stakeholders. RESULTS: Definitive rheumatological treatment comprises a package
      of care rather than a single action. The care package usually requires input from
      a multidisciplinary team using several modalities in parallel. Actions within the
      care package that must be taken before treatment can be said to have started, are
      definitive actions. Definitive actions should be based on evidence of cost
      effectiveness, tailored to the individual patient and offered irrespective of
      local availability or accessibility. They should be agreed between partners in
      the patient's care. This requires face-to-face consultation between the patient
      and a health care professional with appropriate expertise and knowledge. All
      definitive actions specified at the outset of management within specialist care
      must be initiated or removed by agreement from the patient's care package before
      the clock can be stopped in the 18-week-patient pathway. CONCLUSIONS: Service
      redesign may be necessary in order to achieve an 18-week-patient pathway for all
      patients. A consistent and appropriate definition of clock-stops should ensure
      that patients will benefit from excellent rheumatology specialist care without
      unnecessary delay.

PMID- 17500077
TI  - Expression of B-cell activating factor of the tumour necrosis factor family
      (BAFF) in T cells in active systemic lupus erythematosus: the role of BAFF in T
      cell-dependent B cell pathogenic autoantibody production.
AB  - OBJECTIVES: To determine whether B cell activating factor of the tumour necrosis
      factor family (BAFF) is involved in T cell-dependent B cell pathogenic
      autoantibody production in systemic lupus erythematosus (SLE). METHODS:
      Peripheral blood mononuclear cells (PBMCs) from 23 SLE patients were analysed by
      flow cytometry to examine the intracellular expression of BAFF in CD4+ and CD8+ T
      cells and the surface expression of BAFF-receptor (R) and TACI on CD20+ B cells.
      Moreover, peripheral blood was used to determine the level of BAFF messenger RNA
      (mRNA) in CD4+ and CD8+ T cells and the level of BAFF-R mRNA in CD20+ B cells.
      Blocking of BAFF function with TACI-Ig measured anti-double-stranded DNA (dsDNA)
      antibodies by enzyme-linked immunosorbent assay (ELISA). RESULTS: CD4+ and CD8+ T
      cells from patients with active SLE expressed intracellular BAFF whereas those
      from normal subjects did not. BAFF-R and TACI were expressed on B cells from both
      normal controls and patients with active SLE and there was no significant
      difference. CD4+ and CD8+ T cells from SLE patients expressed BAFF mRNA whereas
      those from normal controls did not. Expression of BAFF-R mRNA in CD20+ B cells
      showed no significant difference between SLE patients and normal controls. TACI
      Ig suppressed spontaneous in vitro T cell-dependent B cell anti-dsDNA antibodies
      production on active SLE with kidney involvement. CONCLUSIONS: BAFF may play a
      pathogenic role in SLE by stimulating T cell-dependent B cell autoantibodies
      production. Blockade of BAFF is a promising therapeutic approach for SLE
      especially in patients with kidney involvement.

PMID- 17500079
TI  - The role of MRI in the assessment of polymyositis and dermatomyositis.
AB  - OBJECTIVES: Acute inflammation in idiopathic inflammatory myopathies (IIM) causes
      oedema that can be visualized by magnetic resonance imaging (MRI). The
      inflammatory infiltrate in IIM is thought to be frequently in a focal
      distribution. The aim of this study is to better evaluate the relationship of MR
      image of thigh muscles to clinical and histological parameters in patients with
      IIM. METHODS: MRI-short tau inversion recovery (STIR) technique was used to
      distinguish between affected and non-affected muscles. Computer tomography (CT)
      controlled targeted needle biopsy was used for sampling. The intensity of muscle
      oedema, its extent and total assessment on MRI were evaluated with 10 cm visual
      analogue scale. The intensity of inflammatory infiltrate was assessed using 5
      point grading system. The second MRI and muscle biopsy were performed after the
      time interval of treatment. RESULTS: MR scans, muscle biopsy and clinical
      examination were performed in 29 patients with polymyositis (PM) and
      dermatomyositis (DM). Paired MRI-affected and MRI-non-affected biopsy samples
      were obtained from 17 cases. In six cases, the biopsy was available for
      comparison before and after period of treatment. At the initial examination, it
      was the intensity of oedema on MRI that was associated with clinical status. Mean
      intensity of MRI findings significantly decreased in 10 patients where the MRI
      was available also after treatment. The mean intensity of inflammatory infiltrate
      in PM/DM patients was 2.5 +/- 0.7 for MRI-affected and 1.7 +/- 0.6 for MRI-non
      affected muscles (P < 0.001). Mean intensity of inflammatory infiltrate in the
      MRI-affected muscles in the first examination (n = 6) was 2.2 +/- 0.8 and did not
      significantly decrease in the second examination in samples taken after the
      treatment (2.0 +/- 0.9). CONCLUSION: It is mainly the signal intensity in MR
      scan, which is associated with disease activity in the acute presentation of
      PM/DM. Muscle biopsy guided by positive MRI finding contains significantly more
      inflammatory cells than the biopsy taken from MRI non-affected sites. However,
      even in parts of muscles, which look unaffected on MR scan, the inflammatory
      cells can be found. The intensity on MR scans decreases significantly after the
      treatment, but the histologically detected inflammation does not change
      substantially.

PMID- 17500080
TI  - Experience with office-based pulsed-dye laser (PDL) treatment.

PMID- 17500081
TI  - Mayo Clinic research targets improved heart stent safety.

PMID- 17500082
TI  - What's for lunch? Tips for making healthy choices.

PMID- 17500083
TI  - Is it true that cinnamon can lower blood sugar in people with diabetes?

PMID- 17500084
TI  - When I fly eastward across the ocean, I find it's more difficult to adjust to the
      time change  than when I return home on the westward trans-Atlantic flight. Why
      is jet lag different with east versus west travel, and what can I do to recover
      from jet lag?

PMID- 17500085
TI  - Could smoking less be safe?

PMID- 17500086
TI  - 5 questions to help your pharmacist help you.

PMID- 17500087
TI  - Ask the doctors. I have peripheral arterial disease. My doctor told me I need to
      walk more, but it causes a lot of pain in my muscles when I do. Is there any risk
      of harm to my legs or feet from walking too much?

PMID- 17500088
TI  - Ask the doctors. I am a 47-year-old man. If my two older brothers have coronary
      disease, do I have any chance of not running into the same problem?

PMID- 17500089
TI  - Ask the doctor. I have read good news about nattokinase and would like to use it
      to keep my blood thin. Is it a good substitute for aspirin?

PMID- 17500090
TI  - Ask the doctor. Is it true that angioplasty and stenting are dangerous for women?

PMID- 17500091
TI  - Ask the doctor. I am a woman in my 60s who just underwent angioplasty and
      stenting. I feel great. My doctor want me to go to a cardiac rehabilitation
      program. Do I really need it?

PMID- 17500092
TI  - Ask the doctor. I know the omega-3 fatty acids in fish are good for your heart,
      but I don't like fish. Can I take omega-3 supplements instead?

PMID- 17500093
TI  - Invertebrate preparations and their contribution to neurobiology in the second
      half of the 20th century.
AB  - This review summarized the contribution to neurobiology achieved through the use
      of invertebrate preparations in the second half of the 20th century. This
      fascinating period was preceded by pioneers who explored a wide variety of
      invertebrate phyla and developed various preparations appropriate for
      electrophysiological studies. Their work advanced general knowledge about
      neuronal properties (dendritic, somatic, and axonal excitability; pre- and
      postsynaptic mechanisms). The study of invertebrates made it possible to identify
      cell bodies in different ganglia, and monitor their operation in the course of
      behavior. In the 1970s, the details of central neural circuits in worms,
      molluscs, insects, and crustaceans were characterized for the first time and well
      before equivalent findings were made in vertebrate preparations. The concept and
      nature of a central pattern generator (CPG) have been studied in detail, and the
      stomatogastric nervous system (STNS) is a fine example, having led to many major
      developments since it was first examined. The final part of the review is a
      discussion of recent neuroethological studies that have addressed simple
      cognitive functions and confirmed the utility of invertebrate models. After
      presenting our invertebrate "mice," the worm Caenorhabditis elegans and the fruit
      fly Drosophila melanogaster, our conclusion, based on arguments very different
      from those used fifty years ago, is that invertebrate models are still essential
      for acquiring insight into the complexity of the brain.

PMID- 17500094
TI  - Nitric oxide in the injured spinal cord: synthases cross-talk, oxidative stress
      and inflammation.
AB  - Nitric oxide (NO) is a unique informational molecule involved in a variety of
      physiological processes in the central nervous system (SNS). It has been
      demonstrated that it can exert both protective and detrimental effects in several
      diseases states of the CNS, including spinal cord injury (SCI). The effects of NO
      on the spinal cord depend on several factors such as: concentration of produced
      NO, activity of different synthase isoforms, cellular source of production and
      time of release. Basically, it has been shown that low NO concentrations may play
      a role in physiologic processes, whereas large amounts of NO may be detrimental
      by increasing oxidative stress. However, this does not explain all the
      discrepancies evidenced studying the effects of NO in SCI models. The analysis of
      the different synthase isoforms, of their temporal profile of activation and
      cellular source has shed light on this topic. Two post-injury time intervals can
      be defined with reference to the NO production: immediately after injury and
      several hours-to-days later. The initial immediate peak of NO production after
      injury is due to the up-regulation of the neuronal NO synthase (nNOS) in resident
      spinal cord cells. The late peak is due primarily to the activity of inducible
      NOS (nNOS) produced by inflammatory infiltrating cells. High NO levels produced
      by up-regulated nNOS and iNOS are neurotoxic; the down-regulation of nNOS
      corresponds temporally to the expression of iNOS. On the bases of the evidence,
      therapeutic approaches should be aimed: (1) to reduce the NO-elicited damage by
      inhibition of specific synthases according to the temporal profile of activation;
      (2) by maintaining physiologic amount of NO to keep the induction of iNOS.

PMID- 17500095
TI  - Central mechanisms in phantom limb perception: the past, present and future.
AB  - Phantom limbs provide valuable insight into the mechanisms underlying bodily
      awareness and ownership. This paper reviews the complexity of phantom limb
      phenomena (proprioception, form, position, posture and telescoping), and the
      various contributions of internal constructs of the body, or body schema, and
      neuromatrix theory in explaining these phenomena. Specific systems and processes
      that have received little attention in phantom limb research are also reviewed
      and highlighted as important future directions, These include prosthesis
      embodiment and extended physiological proprioception (i.e., the extension of the
      body's "area of influence" that thereby extends one's innate sense of
      proprioception, mirror neurons and cross-referencing of the phantom limb with the
      intact limb (and the related phenomena of perceiving referred sensations and
      mirrored movements in the phantom form the intact limb). The likely involvements
      of the body schema and the body-self neuromatrix, mirror neurons, and cross
      callosal and ipsilateral mechanisms in phantom limb phenomena all suggest that
      the perception of a "normal" phantom limb (that is, a non-painful phantom that
      has the sensory qualities of an intact limb) is more than likely an epiphenomenon
      of normal functioning, action understanding and empathy, and potentially may even
      be evolutionarily adaptive and perhaps necessary. Phantom pain, however, may be a
      maladaptive failure of the neuromatrix to maintain global bodily constructs.

PMID- 17500096
TI  - Flu fighters. $161 million goes to six hospitals for research centers.

PMID- 17500097
TI  - Wanted: ASC payment changes. But trade groups differ on how to alter the system.

PMID- 17500098
TI  - E-prescribing disconnect. Despite potential benefits, few physicians use tool.

PMID- 17500099
TI  - [Drug administration via catheter].

PMID- 17500100
TI  - Cancer prevention or parents' rights?

PMID- 17500101
TI  - Implication of protocadherin-PC in the progression of the advanced prostate
      cancer.

PMID- 17500102
TI  - Dracunculiasis eradication: certification of interruption of transmission.

PMID- 17500104
TI  - New WHO online tool to improve clinical trial transparency.

PMID- 17500103
TI  - Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine
      viruses developed for potential use as pre-pandemic vaccines, March 2007.

PMID- 17500105
TI  - NNRTI data in naive patients.

PMID- 17500106
TI  - African-American women needed for study.

PMID- 17500107
TI  - Hopes dashed for HCV drug.

PMID- 17500108
TI  - [The changing representations of social work during the 20th century].

PMID- 17500109
TI  - [Kinsey in France: feminine and masculine sexualities under debate].

PMID- 17500110
TI  - [1950's-60's representations of the feminine in two women's journals, one
      Catholic and one Protestant: La Femme dans la Vie Sociale and Jeunes Femmes].

PMID- 17500111
TI  - [Algerian women and exemplary French mothers, 1945-62].

PMID- 17500112
TI  - [Sower, inseminator, and faithful fighter for the future; or, masculinity in
      Austrian social democracy, 1888-1934].

PMID- 17500113
TI  - [A new challenge. Treating the feminine and masculine equally: or, from women's
      history to the "history of all the boys and girls"].

PMID- 17500114
TI  - The first amputation in Australia.

PMID- 17500115
TI  - The commercialisation of medicine in the popular press: English almanacs 1640
      1700.

PMID- 17500116
TI  - "Fruitation was the question in debate": pro and contra the Renaissance orgasm.

PMID- 17500117
TI  - Witches and fairies in early-modern Scotland.

PMID- 17500118
TI  - Animals, extraterrestrial life and anthropocentrism in the seventeenth century.

PMID- 17500119
TI  - [The development of Joseph Stalin's housing system in St. Petersburg].

PMID- 17500120
TI  - What the U.S. BMET Board of Examiners look for in a journal.

PMID- 17500121
TI  - Monitoring of Risedronate by biochemical bone markers in clinical practice.
AB  - The study of trend of Risedronate 10 mg/day in menopausal women with a high level
      of resorptive bone marker (Betacrosslaps, CTx) by the following bone markers:Bone
      alkaline phosphatase (formation marker) total alkaline phosphatase (TAlP), NMID
      osteocalcin, undercarboxylated osteocalcin (UcOC) and procollagen type 1 carboxyl
      propeptides (PICP). Risedronate does not suppress bone resorption deeply that
      enhances the bone recovers quickly after withdrawal. The level of
      undercarboxylated osteocalcin was increased after one year of treatment; it may
      be a sign of vitamin K2 deficiency. The bone alkaline phosphatase was decreased
      at the end of 12 months and Procollagen type 1 carboxyl propeptides (PICP) of
      twelfth month changed significantly compared to the sixth months of treatment
      (p=0.001) The once week 70 mg/week group also changed of CTx the same as daily
      dose group.

PMID- 17500122
TI  - [Housing in Soviet cities between the revolution and the 1930's].

PMID- 17500123
TI  - [The 1935 general reconstruction plan for Moscow and the transformation of the
      historic city center].

PMID- 17500124
TI  - [Rural-urban land conversion in tropical Africa: received concepts].

PMID- 17500125
TI  - [Urbanization and food security in Niamey, Niger].

PMID- 17500126
TI  - "We are bought like clothes": the war over polygyny and levirate marriage in
      South Sudan.

PMID- 17500127
TI  - Sport or political organization? Structures and characteristics of the Red Sport
      International, 1921-1937.

PMID- 17500128
TI  - [Brazilian physician Jose Pinto de Azeredo (1766?-1810) and the chemical
      examination of Rio de Janeiro's atmosphere].
AB  - Jose Pinto de Azeredo, of Rio de Janeiro, studied medicine and conducted notable
      experimental research in Edinburgh (1786-88), presenting his graduate thesis on
      gout in Leiden. Already appointed surgeon-general of Angola, he returned to Rio
      in 1789 and practiced medicine in Brazil. In 1790 he moved to Luanda, where he
      practiced at the Hospital Real and founded a medical school that did not survive
      his departure for Portugal in 1797. He worked at Lisbon's main military hospital
      and as a private physician until his death. His written works (some ten
      manuscripts and five publications) warrant an examination from the perspective of
      the history of medicine. In an article published in 1790 on Rio de Janeiro's air
      quality, he reveals the skills of an analytical chemist, his interest in the
      effects of different air components on organisms, and his concern with air
      quality in Brazil and Europe.

PMID- 17500129
TI  - [For the good of the nation's economy: therapeutic work and public assistance at
      La Castaneda asylum in Mexico City, 1929-32].
AB  - Founded in 1910, by 1930 Mexico City's La Castaneda insane asylum was grappling
      with the problem of a massive number of chronic patients, a situation that earned
      it an image as a warehouse for the sick more than a place of treatment.
      Psychiatrists endeavored to restore the asylum's legitimacy by publicizing a
      nineteenth-century treatment which projected the public image that the mentally
      ill could be as productive as anyone else: work therapy. The government born of
      the Mexican revolution supported this proposal because the guiding objective
      behind public assistance for underprivileged groups was to make them part of the
      country's productive life via the market.

PMID- 17500130
TI  - [Ways of managing madness during the First Republic: the case of the state of
      Espirito Santo].
AB  - The article explores the creation of institutions for managing madness and the
      'mad' under the First Republic. By focusing specifically on the state of Espirito
      Santo, it analyzes how the government designed policies for dealing with the mad
      and asks whether this particular state's experience can validate hypotheses
      defended for the nation as a whole. The study also aims to demonstrate the
      complex relations between madness, society, medicine, and the State. A main
      discussion point is the process by which medicine was transformed into hegemonic
      knowledge and practice used to justify and validate government guardianship of
      the mad.

PMID- 17500131
TI  - [Ethics and medicine in Michel Foucault: the humanistic dimension of medicine
      derived from a genealogy of morality].
AB  - The article presents the results of a doctoral dissertation defended at the
      Universidad de Salamanca, based on Foucault's final decade of writings. If
      Foucault's goal in writing The History of Sexuality was to fashion a genealogy of
      ethics, my goal in analyzing this book, along with his other writings, is to
      demonstrate his last contribution to the history of medicine. He moves from a
      conception of power over others towards a conception of power over oneself, an
      exclusive terrain of ancient Greek morality. As a thinker who tries to understand
      today's problems by going to their roots, Foucault develops less a history than a
      philosophy of history. Considered an anti-humanist, he leaves us with a portrait
      of a wholly ethical-humanistic medicine.

PMID- 17500132
TI  - [Ethics and epidemiology].
AB  - Human actions take place at the confluence of circumstances that require us to
      discern the proper way to act. Ethics falls within the terrain of practical
      knowledge, of knowledge about what is contingent. It belongs to the domain of
      moral judgments or value judgments. The counterpart of disenchantment with our
      contemporary world lies in an effort to re-establish an interest in ethics. There
      are basically three orders of relations between public health and human rights:
      the quest for balance between the collective good and individual rights; methods
      and techniques for identifying human rights violations and assessing their
      negative impact; and the tie between protecting individual rights and promoting
      health. The relationship between ethics and epidemiology goes beyond the ethical
      aspects involving research on human beings to encompass political commitments,
      practices within health services, and the production of knowledge.

PMID- 17500133
TI  - [Globalization and environmentalism: polyphonic ethnicities in the Amazon].
AB  - The article examines the issue of globalization, along with its contradictions
      and the ways in which it guides and shapes specific situations within the
      Amazon's present-day reality, while simultaneously engendering the uniformization
      of economic production and the valorization of cultural differences. The
      discussion explores the nuances of implementing a massified, standardized
      productive base that paradoxically fosters the valorization of cultural
      differences and favors alliances between, on the one hand, ethno-political
      leaders from indigenous Amazon groups and, on the other, environmentalists and
      other transworld actors who wield strong decision-making power. The article
      analyzes the indigenous movement's network of alliances and highlights the
      polyphony of the different political agents that come to clash with each other
      within this post-modern geopolitical setting.

PMID- 17500134
TI  - [On two antique medical texts].
AB  - The two texts presented here--Regimento proueytoso contra ha pestenenca
      [literally, "useful regime against pestilence"] and Modus curandi cum balsamo
      ["curing method using balm"]--represent the extent of Portugal's known medical
      library until circa 1530, produced in gothic letters by foreign printers:
      Germany's Valentim Fernandes, perhaps the era's most important printer, who
      worked in Lisbon between 1495 and 1518, and Germdo Galharde, a Frenchman who
      practiced his trade in Lisbon and Coimbra between 1519 and 1560. Modus curandi,
      which came to light in 1974 thanks to bibliophile Jose de Pina Martins, is
      anonymous. Johannes Jacobi is believed to be the author of Regimento proueytoso,
      which was translated into Latin (Regimen contra pestilentiam), French, and
      English. Both texts are presented here in facsimile and in modern Portuguese,
      while the first has also been reproduced in archaic Portuguese using modern
      typographical characters. This philological venture into sixteenth-century
      medicine is supplemented by a scholarly glossary which serves as a valuable tool
      in interpreting not only Regimento proueytoso but also other texts from the era.
      Two articles place these documents in historical perspective.

PMID- 17500136
TI  - [Regimento proueytoso and Modus curandi: edition of the texts].
AB  - This issue features facsimiles of Regimento proueytoso contra ha pestenenca and
      Modus curandi cum balsamo, based on the original texts housed in the Biblioteca
      Publica de Evora and the Biblioteca Nacional de Portugal, respectively. Semi
      diplomatic editions of both facsimiles--with transliterations into modern
      characters--have also been provided. These are followed by translations, in the
      case of Regimento from old to modern Portuguese and in the case of Modus curandi
      from Latin to modern-day Portuguese. This text explains the criteria used in
      preparing the semi-diplomatic versions and in modernizing the text of Regimento.

PMID- 17500137
TI  - [Regimento proueytoso contra ha pestenenca. Semidiplomatic edition/updated
      edition].

PMID- 17500139
TI  - [General observations on the treatise Modus curandi cum balsamo].
AB  - Modus curandi cum balsamo is a short text, printed circa 1530 and written by an
      unknown author in Vulgar Latin from the Iberian peninsula. Its value stems first
      from the fact that it was one of the first medical texts printed in Portugal. But
      other aspects definitely reinforce this importance. As the title indicates, the
      text describes a balm that can cure very deep wounds. The prescription is
      strange, and even stranger is the propagandizing tone of this brief treatise. The
      prescription comes with recommendations on how to apply the remedy, especially to
      the cranium. Reference is made to a wound that goes from the dura mater to the
      "substance" of the head; according to the treatise, this wound should first be
      drained before applying the balm.

PMID- 17500140
TI  - [Modus curandi: a diplomatic edition].

PMID- 17500141
TI  - [Useful regime against the plague (ca. 1496)--an introduction].
AB  - This introductory text analyzes Regimento proveitoso contra a pestilencia,
      written in Portugal around 1496. The work is situated within the context of the
      era's main theories and of medieval medical thought, based on the Arab tradition.

PMID- 17500142
TI  - [Regime for treating the plague and the prescription of balm: some comments from
      the perspective of 'modern medicine'].
AB  - Regimento proueytoso contra ha pestenenca and Modus curandi cum balsamo are
      probably the first texts addressing the prevention and treatment of diseases to
      be printed in Portugal. Their authorship and historical context are discussed
      elsewhere in this journal. Here we would like to raise some questions concerning
      the 'medical discourse' found in the texts and compare these with others from the
      eighteenth century. The authors chosen for the sake of comparison are two
      Portuguese--Luiz Gomes Ferreyra and Joao Curvo Semmedo--and one Englishman, John
      Huxham, author of An Essay on Fevers, which includes a lengthy discussion of
      smallpox, Europe's eighteenth-century 'plague'. It is our belief that these
      works, written in the early days of 'scientific medicine', represent a bridge
      between medieval/Renaissance texts and current medical compendia. They allow us
      to raise questions about the therapeutic indications and diagnostic criteria
      found in the documents.

PMID- 17500143
TI  - [Regimento proueytoso contra ha pestenenca. Glossary].
AB  - The main goal of the following glossary is to work as a support to the reading of
      Regimento proueytoso contra ha pestenenca. For this reason it includes every word
      in the text. However, since it may interest one concerned with the history of
      Portuguese, the glossary was supplied with additional information on orthography
      and on the original form of the words.

PMID- 17500144
TI  - [History of the first institutions for the insane in Brazil].
AB  - The article presents research findings on the institutionalization of the insane
      in five provinces of colonial Brazil: Sao Paulo, Rio Grande do Sul, Maranhao,
      Pernambuco, and Para. Reports by the presidents of these provinces, written
      during the Segundo Reinado (1846-89), were analyzed. In these documents, insanity
      is viewed as a special disease, and it is indicated that the mad are not meant to
      be kept among other ill people, much less in jail. The reports also register
      societal pressure to have such people committed. These politicians adopted the
      medical discourse on insanity, but their descriptions of asylums evince the
      contradiction between an alleged social-assistance project based on suppositions
      drawn from Pinel and the outright seclusion that was actually practiced.

PMID- 17500148
TI  - [Day nurseries in all their forms].

PMID- 17500149
TI  - [Collective welcome as a means of educating children].

PMID- 17500150
TI  - [Regulation of centers caring for children less than six months old].

PMID- 17500151
TI  - [Admitting a child and his family to a day nursery].

PMID- 17500152
TI  - [The value of an educational project in a day nursery].

PMID- 17500153
TI  - [Respecting the biological rhythms in the child].

PMID- 17500154
TI  - [Chanteloup-Les-Vignes day nursery, an admission and integration place].

PMID- 17500155
TI  - [Barbanniers day nursery, an example of an entrepreneurial center].

PMID- 17500156
TI  - [Serological follow-up of child sexual abuse victims in a forensic unit].

PMID- 17500157
TI  - Problem-based learning in dental education: what's the evidence for and
      against...and is it worth the effort?
AB  - All Australian dental schools have introduced problem-based learning (PBL)
      approaches to their programmes over the past decade, although the nature of the
      innovations has varied from school to school. Before one can ask whether PBL is
      better than the conventional style of education, one needs to consider three key
      issues. Firstly, we need to agree on what is meant by the term PBL; secondly, we
      need to decide what "better" means when comparing educational approaches; and
      thirdly, we must look carefully at how PBL is implemented in given situations. It
      is argued that PBL fulfils, at least in theory, some important principles
      relating to the development of new knowledge. It also represents a change in
      focus from teachers and teaching in conventional programmes to learners and
      learning. Generally, students enjoy PBL programmes more than conventional
      programmes and feel they are more nurturing. There is also some evidence of an
      improvement in clinical and diagnostic reasoning ability associated with PBL
      curricula. The main negative points raised about PBL are the costs involved and
      mixed reports of insufficient grounding of students in the basic sciences.
      Financial restraints will probably preclude the introduction of pure or fully
      integrated PBL programmes in Australian dental schools. However, our research and
      experience, as well as other published literature, indicate that well-planned
      hybrid PBL programmes, with matching methods of assessment, can foster
      development of the types of knowledge, skills and attributes that oral health
      professionals will need in the future.

PMID- 17500158
TI  - Recurrent aphthous ulcerative disease: presentation and management.
AB  - Recurrent aphthous ulceration (RAU) is the second most common type of ulceration
      seen in the oral cavity. Notwithstanding an extensive literature and numerous
      proposed aetiologies, the cause of the disease remains obscure. In addition to
      the current conservative management of RAU lesions with corticosteroids, new
      treatment options are available and some have proven successful in open trials.
      This paper reviews patient work-up and management.

PMID- 17500159
TI  - Differences between normal and demineralized dentine pretreated with silver
      fluoride and potassium iodide after an in vitro challenge by Streptococcus
      mutans.
AB  - BACKGROUND: The application of diamine silver fluoride (Ag(NH3)2F) and potassium
      iodide (KI) to demineralized dentine has been shown to inhibit the growth of
      Streptococcus mutans. The purpose of this study was to observe the differences
      between demineralized and non-demineralized dentine treated with AgF/KI. METHODS:
      Thirty-five dentine discs were bonded to the bases of 5 mL polycarbonate screw
      top vials which were filled with nutrient medium, sterilized and placed into the
      overflow from a continuous culture of S. mutans. Samples were divided as follows:
      10 samples of demineralized dentine; 10 samples of demineralized dentine treated
      with AgF/KI; 5 samples of non-demineralized dentine; and 10 samples of non
      demineralized dentine treated with AgF/KI. Following two weeks connected to the
      Chemostat, an electron probe microanalysis (EPMA) of percentage weights and
      penetration depths of calcium, phosphorous silver and fluoride was conducted.
      Bacterial growth was monitored by taking optical density readings of the growth
      medium in each vial and outer surfaces of the specimens were examined by scanning
      electron microscopy (SEM). RESULTS: AgF/KI treatment of demineralized and non
      demineralized dentine prevented biofilm formation and reduced further
      demineralization by S. mutans. AgF/KI treatment of demineralized dentine was more
      effective in reducing dentine breakdown and the growth of S. mutans.
      Significantly higher levels of silver and fluoride were deposited within
      demineralized dentine. CONCLUSIONS: A topical treatment with AgF/KI on dentine
      reduced in vitro caries development and inhibited surface biofilm formation.
      Reduction of in vitro caries development and viability of S. mutans was more
      pronounced on the dentine samples that had been demineralized prior to the
      application of

PMID- 17500160
TI  - Non-working dental therapists: opportunities to ameliorate workforce shortages.
AB  - BACKGROUND: Workforce development is acritical factor allowing delivery on
      government health priorities. Against a backdrop of increasingdemand for dental
      therapists being significantly higher than the levels of recruitment, it is
      widely acknowledged that rural and remote areas (having greater recruitment and
      retention issues) will face significant shortfall in therapist numbers as the
      workforce shortages take hold in dentistry. This study analysed the reasons for
      dental therapists leaving the profession, and factors that would promote the
      recruitment and retention of dental therapists, especially in rural and remote
      areas. METHODS: A postal survey was undertaken amongst all registered dental
      therapists in Western Australia between the years 1999-2003. RESULTS: Of all
      respondents, 28 per cent indicated that they do not work as dental therapists
      anymore. A number of reasons for leaving the profession were highlighted,
      including family reasons, careerchange, poor salaries, relocation, illness and
      injury, and stress. To increase retention and recruitment of dental therapists to
      rural areas, a number of opportunities were highlighted by respondents, including
      increased salaries, living support, travel assistance, access to continuing
      education, recruitment of more rural students and more flexibility (including job
      sharing). CONCLUSION: This survey has highlighted various opportunities to
      recruit and retain dental therapists in their profession and to increase the
      numbers of rural dental therapists. A broad integrated rural retention strategy
      is necessary to address these issues among the dental therapy workforce.

PMID- 17500161
TI  - A longitudinal study of 0.2% chlorhexidine gel for removal of mutans streptococci
      infection in preschool children.
AB  - BACKGROUND: The purpose of the present longitudinal study was to determine the
      effectiveness of 0.2% chlorhexidine (CHX) in removing mutans streptococci (MS) in
      a treatment cohort of caries-free, preschool children. METHODS: Thirty-six
      children with mean age 38.6 +/- 15.9 months who had MS infection brushed once
      daily with 0.2% chlorhexidine (CHX) gel for a period of 6-12 months. The children
      were examined every three months to assess their oral hygiene and dietary habits
      and MS status using a commercial microbiological kit. RESULTS: The percentages of
      children who eliminated MS from their mouths increased from 28 per cent after
      three months to 48 per cent after six months and over 70 per cent after 12 months
      of gel use (p = 0.039). Compliance of brushing with CHX gel was significantly
      associated with MS removal after six months gel use (p < 0.02). At the three and
      six month recalls, sugar snacks and increased sugar frequency were associated
      with continued presence of MS (p = 0.03 and p = 0.007). After three months
      cessation of CHX use, 13 (45 per cent) remained MS free (p = 0.003). CONCLUSIONS:
      This pilot study involving caries-free preschoolers with MS shows the potential
      of chlorhexidine gel to remove MS for the limited duration of study.

PMID- 17500162
TI  - Evaluation of a combined thiourea and hydrogen peroxide regimen to bleach
      bloodstained teeth.
AB  - BACKGROUND: Current techniques for intra-coronal bleaching of stained root-filled
      teeth employ oxidative bleaching with hydrogen peroxide. However, concern over
      the potential for invasive cervical resorption following the use of hydrogen
      peroxide has been expressed by many researchers, and recommendations have been
      made to limit the use of this agent. A reductive-oxidative bleaching process
      using a thiourea and hydrogen peroxide regimen is proposed as an effective and
      safer bleaching combination. The efficacy of this novel bleaching regimen is
      evaluated in this study. METHODS: The study involved a quantitative and
      qualitative spectrophotometric assessment of the ability of two amine (bleaching)
      agents, aqueous thiourea and acidified thiourea, to alter the absorption spectra
      of haemoglobin and methaemoglobin compared to hydrogen peroxide. In addition,
      extracted premolar teeth discoloured by blood were subjected to different
      bleaching regimens using amine reducing agents and hydrogen peroxide. The change
      in the colour of the bloodstained dentine samples was measured at each stage of
      the bleaching process with a Photometer and Reflectance Densitometer. Comparisons
      of different treatments were made using a method of least significant difference
      and/or analysis of variance. RESULTS: Spectrophotometric studies showed that
      acidified thiourea solution greatly reduced the colour of the haemoglobin and
      methaemoglobin in the visible range (330-760 nm). Aqueous thiourea had no effect
      on the presence of haemoglobin and methaemoglobin. Reflection Densitometer and
      Photometer scores indicate that the greatest bleaching effect was achieved by the
      combined acidified thiourea and hydrogen peroxide regimen. CONCLUSION: The
      recognition that bleaching discoloured teeth is a chemical process, which can be
      achieved by both reducing and oxidizing agents, offers the possibility of
      developing new and safer clinical bleaching protocols. It is concluded that the
      bleaching regimen which employs the sequential use of 0.1 M acidified thiourea
      and 30% w/v hydrogen peroxide is as effective at bleaching bloodstained dentine
      as 30% w/v hydrogen peroxide alone. However, the addition of thiourea to the
      bleaching regimen has the potential benefit of reducing the level of damaging
      hydroxyl radicals and achieving a safer bleaching process.

PMID- 17500163
TI  - Comparative uptake of fluoride ion into enamel from various topical fluorides in
      vitro.
AB  - BACKGROUND: There are many forms of topical fluoride available today, making the
      decision as to which is most effective to manage the immediate caries risk
      problem at hand, very difficult. The objective of this project was to determine
      the concentration and pattern of fluoride ion uptake into enamel from a variety
      of categories of topical fluoride recently available in Australia. METHODS:
      Extracted, intact molar teeth were sectioned to provide six plates of smooth
      surface enamel. Windows of enamel 2 x 6 mm were exposed to a variety of topical
      fluorides for periods simulating those used in vivo. Following drying, the slates
      of enamel were exposed to 2 ml of 0.1 M HCl as a chemical biopsy agent for
      incremental periods of time. The concentrations of fluoride ion in the biopsy
      solutions for both test and background (control) slates of enamel were determined
      directly using a fluoride combination selective electrode in conjunction with a
      high impedance pH meter. Cumulative amounts of fluoride were determined for each
      topical fluoride agent. RESULTS: The concentrations of fluoride ion taken up into
      enamel were generally proportional to those present in each agent. However, those
      from APF gel greatly exceeded the amounts taken up from NaF gel. Also, the
      concentrations taken up from some of the highly concentrated metal fluorides were
      surprisingly low. Prior etching of enamel increased uptake and prolonged
      application of APF gel provided no extra benefit. CONCLUSIONS: Some topical
      fluorides, e.g., APF gel, provided a greatly increased uptake and to a greater
      depth than other self-application products. However, the frequency of its use
      should be considered with caution where patients have glass-based restorations.

PMID- 17500164
TI  - Different bone loading patterns due to fixation of three-unit and five-unit
      implant prostheses.
AB  - BACKGROUND: It has been considered that implant prostheses ought to display
      passive fit. The objective of this finite element analysis (FEA) was to simulate
      the bone loading resulting from the fixation of implant-supported three and five
      unit fixed partial dentures (FPDs). METHODS: Based on a patient case, six
      different FPD-groups were fabricated using either two or three implants for
      support. Strain gauges on the pontics of the prostheses were used for in vivo
      measurements. Based on the values obtained, bone loading models were simulated
      using three-dimensional finite element analysis and the results obtained were
      represented as von Mises equivalent stress. RESULTS: The mean strain (epsilon)
      values ranged from 15 micro epsilon to 170 micro epsilon for the three-unit FPDs
      and from 32 micro epsilon to 302 micro epsilon for the five-unit FPDs. FEA
      revealed von Mises stresses up to 30 MPa in the cortical area, while in
      trabecular bone values up to 5 MPa were observed. Static implant loading of
      similar magnitude can be provoked through 200 N axial load. CONCLUSIONS: Although
      the in vivo measured strain levels (epsilon) were of higher magnitude for the
      five-unit prostheses, FEA revealed bone loading of comparable magnitude for both
      three- and five-unit FPDs. Multi-unit prostheses may demonstrate greater
      inaccuracies compared with single implant restorations, but due to the absence of
      moment loading the multi-implant configuration appears to compensate for the
      higher strain development.

PMID- 17500165
TI  - Periodontal disease among 45-54 year olds in Adelaide, South Australia.
AB  - BACKGROUND: The aims of this study were to describe the prevalence, extent and
      severity of periodontal disease among middle-aged adults, and to examine
      periodontitis by dental visit pattern, dental and health behaviour, socio
      demographics and socioeconomic status. METHODS: A random sample of 45-54 year
      olds from metropolitan Adelaide, South Australia was surveyed by mailed self
      complete questionnaire during 2004-2005 with up to four follow-up mailings of the
      questionnaire to non-respondents (n=879 responded, response rate = 43.8 per
      cent). Oral examinations were performed on 709 people who responded to the
      questionnaire (completion rate=80.7 per cent), providing an assessment of
      periodontal status. RESULTS: Prevalence of loss of attachment (LOA) of 6+ mm was
      19.2 per cent, extent of sites with LOA of 6+ mm was 1.3 per cent, and severity
      of LOA of sites with LOA of 2+ mm was 2.4mm. Using a case definition for
      periodontitis of two or more sites with LOA of 5+ mm and one or more sites with
      PD of 4+ mm in a multivariate logistic regression showed higher odds of
      periodontitis for people who last visited for relief of pain (OR = 1.93) and who
      smoked daily/occasionally (OR = 3.84), while lower odds were observed for people
      who were born in Australia (OR = 0.51) and spoke English as the main language at
      home (OR = 0.34). CONCLUSIONS: While periodontal disease was related to visit
      pattern and health-related behaviours, the relationship with place of birth and
      main language spoken at home indicated socio-cultural variation in disease not
      explained by behaviour among this cohort of 45-54 year olds.

PMID- 17500166
TI  - The implications and management of acute odontogenic infection in association
      with Down and Eisenmenger syndromes and schizophrenia in a rural setting.
AB  - BACKGROUND: This report describes the case management of a 32 year old special
      needs patient with life-threatening odontogenic infection. The combination of
      schizophrenia, Down and Eisenmenger syndromes presented significant challenges to
      managing his oral health, particularly within the rural context. In this case,
      dental treatment was limited to a full dental clearance during a high risk
      general anaesthesia session. METHOD: A comprehensive work-up prior to general
      anaesthesia was an essential aspect of care. This included a full medical history
      and examination, communication between medical specialists, the dentist and
      family consultation. The anaesthetic procedure was undertaken using a careful
      regimen of drugs and monitoring to minimize the impact on his cardiovascular
      system. Techniques to minimize bleeding from extraction sites were also
      important. RESULTS: Three weeks postsurgically the patient was reviewed and his
      family reported that he was interacting positively with them after years of
      surliness and conflict. This was attributed to a managed psychotropic medication
      regimen and improved dental condition, which has led to a sustained improvement
      in quality of life. CONCLUSIONS: The management of acute odontogenic infection
      for special needs patients in the rural setting requires a local
      interdisciplinary team approach, careful consideration of related pathophysiology
      and its potential impact on general anaesthesia, and close consultation with
      family and carers.

PMID- 17500167
TI  - Patterns of care in private general practice by main diagnoses.

PMID- 17500168
TI  - Orofacial trauma in student population of an Indian university.

PMID- 17500169
TI  - [Forensic aspects of laparoscopic surgery].
AB  - There has been a substantial increase in the use of laparoscopic surgery over the
      years as a result of the proven advantages it offers in terms of reduced hospital
      stay, reduced costs, and better esthetic results compared to traditional surgery.
      As regards the issue of professional liability, this kind of procedure calls for
      analysis of major aspects such as indications, the obtaining of informed consent,
      execution, and postoperative course.

PMID- 17500170
TI  - [Laparoscopic cholecystectomy in the day surgery setting].
AB  - The first laparoscopic cholecystectomy in the Department of Surgery of the S.
      Giacomo Hospital in Rome was performed in April 1991. At that time, for the
      complete study of the patient and recovery from the operation, a mean period of
      five days was necessary. Our consolidated experience in laparoscopic
      cholecystectomy now allows us to perform the operation in the one-day surgery
      setting.

PMID- 17500171
TI  - [Length of hospital stay and complications in thyroid surgery. Our experience].
AB  - Length of hospital stays for thyroid surgery has decreased significantly over the
      last years. Hypoparathyroidism is one of the main obstacles to short-stay
      hospitalization. The aim of this study was to evaluate length of hospital stay in
      our experience, its relationship with complications observed and feasibility of
      short-stay hospitalization regimen. Between September 2002 and December 2005, 932
      patients underwent total thyroidectomy in our institution. Serum calcium and
      phosphorus values were obtained at 6 hours after operation and on postoperative
      day 1 and 2. Discharge was possible on the morning of the first postoperative day
      in 2 patients (0.2%), the second day in 687 (73.7%), third day in 167 (17.9%),
      fourth in 44 (4.7%), fifth in 22 (2.4%), after the fifth in 10 (1.1%).
      Complications observed were hypoparathyroidism in 393 patients (42.1%), neck
      hematoma in 12 (1.3%), bilateral recurrent nerve palsy in 5 (0.5%), unilateral
      recurrent nerve palsy in 4 (0.4%), glottic hemorrhagic edema in 1 (0.1%) and
      foreign body granuloma and/or fistula in 5 (0.5%). Hypocalcemia was observed on
      post-operative day 1 in 338 patients (86%), on day 2 in 50 (12.72%) and on day 3
      in 5 (1.27%). Serum calcium and phosphorus determination 6 hours after operation
      and on postoperative day 1 permits an early treatment of hypocalcemia and to
      shorten length of hospital stay. A normal serum calcium level on postoperative
      day 1 lets suppose an easy discharge on the second. Earlier discharge is to be
      reserved to selected patients and not always meets their favour.

PMID- 17500172
TI  - [Acute appendicitis: is this common pathology still of interest?].
AB  - Despite the indisputable progress of technology (laboratory analyses,
      scintigraphy, ultrasonography, computed tomography), the diagnosis of acute
      appendicitis often remains uncertain, with a rate of useless appendectomies
      amounting to almost 20% of cases. The ideal diagnostic test has yet to be
      discovered and, in any case, clinical observation remains the cornerstone of any
      decision-making algorithm. Thus, acute appendicitis continues to offer food for
      thought in relation to the aetiology of the condition, which is still unknown,
      the primacy of the clinical diagnosis, and the learning of the surgical skills
      required. In the present study, the authors compare their personal experience
      with the relevant data in the international literature, emphasising a number of
      issues such as the problem of diagnosis, acute appendicitis in pregnancy,
      laparoscopic therapy, and the so-called "useless appendectomies" and presenting
      their own point of view.

PMID- 17500173
TI  - [Iatrogenic lesions of the common bile duct in laparoscopic cholecystectomy:
      three fundamental requirements for their prevention].
AB  - Laparoscopic cholecystectomy has become the gold standard in the treatment of
      benign biliary disease. Common bile duct injuries are the most serious and feared
      complications of laparoscopic cholecystectomy, since they cause substantial
      morbidity and increased hospital stay, and increasingly often are the subject of
      legal disputes. The causes of these kinds of lesions, according to the
      international literature, are usually inadequate normal and pathological
      anatomical knowledge, an incomplete learning curve, inadequate surgical
      technique, and lastly insufficient compliance of the surgeon. Another important,
      though underestimated, role in the aetiology of these lesions is played by the
      human factor, and particularly by a peculiar preconceived attitude. The latter
      manifests itself as a lack of realism, reasonableness and morality. These three
      basic requirements are part of universal human experience in the dynamics of
      knowing and, although not statistically quantifiable, may play a role comparable
      to that of the technical quality of the surgical performance. In our study we
      have tried to show, with regard to the prevention of biliary lesions during
      laparoscopic cholecystectomy, the extent of the importance of these three
      requirements in the dynamics of knowing, particularly in laparoscopic surgery,
      where they are not adequately taken into consideration. The analysis of the
      profound interaction between these requisites and surgical practice may allow
      correct identification of this preconceived attitude on the part of the operator,
      which can be avoided or minimized only through appropriate surgical training.

PMID- 17500174
TI  - [Incidental gallbladder carcinoma].
AB  - Carcinoma detected at histological examination of the gallbladder is defined as
      incidental. It is a fairly rare event, but the increase in the number of
      cholecystectomies performed has led to a rise in detection of incidental
      gallbladder carcinoma. Histologically, in most cases, these are pT1 and pT2
      carcinomas. Up until the 'nineties it was believed that these carcinomas could be
      adequately treated by simple cholecystectomy, whereas today the treatment of
      choice entails a second operation. This study constitutes a review of 20 years'
      experience. The database consists of 3012 cholecystectomies. Survival data are
      calculated in relation to the evolution of surgical treatment, thus making it
      possible to correlate tumour staging, patient survival and surgical therapy. The
      incidence of IGC was about 0.66% (20 cases). The survival rates of patients
      operated on by extended cholecystectomy, compared with those achieved previously
      with simple cholecystectomy, have risen from 92% to 100% at 1 year and from 26%
      to 66% at 5 years, respectively. The contributions made by literature reports
      since the 'nineties have prompted hepatobiliary surgeons to modify their
      attitudes towards incidental gallbladder carcinoma. Detection of previously
      unrecognised microinfiltrations of the serosa and of neoplastic involvement of
      distant lymph-node stations has led to the introduction of the concept of
      extended cholecystectomy. Comparison between our historical survival curve of
      patients treated with simple cholecystectomy and the distinctly better curve of
      those treated with a radical second operation accounts for the evolution of
      surgical treatment over the past two decades.

PMID- 17500176
TI  - [Complicated diverticular disease of the colon: 5 years' experience in a
      provincial hospital].
AB  - Colon diverticular disease presents in 10%-25% of cases when a complication
      arises. Helped by Hinchey's classification, the surgeon can choose from among the
      following therapeutic strategies: a) medical treatment; b) one-stage resection
      and anastomosis with or without a protective colostomy; and c) resection
      according to Hartmann. The increasingly widespread use of laparoscopic
      techniques, though generally improving surgical outcomes, has perhaps made the
      choice of treatment more difficult, because it has extended the range of
      indications, both in the elective and emergency setting. From January 1999 to
      December 2004 411 patients (174 men and 237 women) affected by symptomatic
      diverticular disease were admitted to our surgical department and 94 of these
      (22.8%) underwent surgery: 41 of them (43.6%) underwent a true emergency
      operation, while for 53 of them surgery was delayed (within one week). None of
      the patients undergoing resection-anastomosis had a protective colostomy. The
      total morbidity was 3.7% and total perioperative mortality 1% (one patient
      undergoing surgery with the Hartmann procedure). More than one year after the end
      of the research there was no need for operation of any of the non-surgical
      patients and no deaths due to diverticular disease were recorded. On the basis of
      our experience we may conclude that a one-stage resection, even in the emergency
      situation, is possible and yields excellent results, while preventive resection
      would not currently seem justified.

PMID- 17500175
TI  - Solitary peritoneal metastases from ductal breast cancer.
AB  - Breast carcinoma remains the most common malignancy in women in western
      countries. The principal sites of metastases are the regional lymph nodes, liver,
      lung and bone; unusual sites of metastases are very rare. Infiltrating ductal
      carcinoma is the most common histological subtype (about 80%) as compared to
      lobular carcinoma (7-20%), which metastasizes more frequently to unusual sites.
      An 80-year-old female patient was submitted to resection of an infiltrating
      ductal carcinoma (stage I). After 4 years, the presence of a pelvic mass in the
      absence of local, distant or lymph node recurrence was found. Resection of the
      mass was performed. The pathological and immunohistochemical examination revealed
      a metastatic carcinoma compatible with a mammalian origin. After 36 months of
      follow-up the patient is alive and disease-free. Considering the age of the
      patient, the good performance status, the absence of other sites of relapse and
      the large size of the mass, surgery was performed. Surgery remains the only valid
      option when recurrence produces abdominal complications. In the absence of
      randomized prospective studies, however, we do not know whether this is always
      the correct therapeutic strategy.

PMID- 17500177
TI  - Large bowel multiple tumours.
AB  - The medical records of all patients with colorectal cancer seen at the "G.
      Marinaccio" Department of Surgery in Bari between 1997 and 2004 were examined.
      Cases included in the study met the criteria advocated by Warren and Gates and
      Moertel et al. Over such period we operated on 103 patients with colon neoplasms,
      mostly males (64 patients) and aged over 65 (64 patients). Both palliative and
      radical operations were performed either as elective treatment or as emergency
      surgery; in some of the latter cases the diagnosis of neoplasm was made casually
      following the final histological test on the operative specimen. Ten cases of
      multiple malignant tumours were recorded, corresponding to 9.7%; in particular 1
      synchronous-metachronous tumour (0.97%), 3 synchronous tumours (2.7%) and 6
      metachronous tumours (5.8%) were observed; two of the metachronous tumours were
      detected in the same patient and one in a patient that had previously been
      operated on for a synchronous carcinoma, thus making a total of 8 patients in
      all. It is concluded that full examination of the colon in all patients
      presenting with primary colorectal cancer is mandatory and that, in the light of
      this experience and recent reports in the literature, this should be done by pre-
      or perioperative colonoscopy. Colonoscopy not only provides accurate detection of
      lesions, but also allows the surgeon to perform polypectomies, thereby obviating
      the need for extending surgery at the time of resection of the coexisting cancer.
      In conclusion, we recommend preoperative colonoscopy for all patients who present
      non-obstructive colorectal neoplasms.

PMID- 17500178
TI  - [Preliminary experience with hyperthermic intraperitoneal chemo-perfusion with
      oxaliplatin for the treatment of peritoneal carcinomatosis due to colorectal
      carcinoma].
AB  - Peritoneal carcinomatosis is the first cause of death after surgery for abdominal
      cancer, with a mean survival of 7 months. In selected patients, aggressive
      cytoreductive therapy combined with hyperthermic intraperitoneal chemotherapy my
      improve medium to long-term survival. Over the period from 2004 to January 2006,
      86 patients were operated on for peritoneal carcinomatosis at the Division of
      Surgical Oncology, Forli, Italy. Thirteen of them were submitted to hyperthermic
      chemotherapy. The authors present their preliminary experience with the treatment
      of colorectal carcinosis by 30-min hyperthermic (41.5-42 degrees C
      intraperitoneal perfusion with oxaliplatin (400 mg/sq.m.) and intravenous 5-FU
      (400 mg/sq.m.) after complete cytoreductive surgery. The average surgical time
      was 606 min (range: 380-765). No intraoperative complications occurred, but 4
      cases of major postoperative morbidity were reported, one of which requiring
      surgery. One patient died 5 months postoperatively due to lung metastases. The
      remaining patients are alive and free from peritoneal disease.

PMID- 17500179
TI  - Bleeding after stapled haemorrhoidopexy using the PPH 03 stapler device.
      Experience and results in 100 consecutive patients.
AB  - Bleeding after stapled haemorrhoidopexy using the PPH 01 device is a relatively
      frequent major complication. Using the new PPH 03 instrument may enable to
      achieve better control. From June 2004 to July 2005, 100 patients with 2nd and
      3rd degree haemorrhoids and mucosal rectal prolapse were treated at our
      institution. In all of the cases the PPH 03 instrument was used and the
      operations were performed by two surgeons with expertise in stapled
      haemorrhoidopexy. During structural interviews, the patients assessed their
      symptoms before and after surgery, and surgical outcome was assessed at 1 and 2
      weeks. Major bleeding (loss of Hb > 5 points) occurred in 2 patients in the first
      10 cases and re-operation was necessary. Minor bleeding (loss of Hb < 3 points)
      occurred in 2 patients. We had 2 bleeds in the early postoperative period (2%)
      and 2 cases of late bleeding (2%). Stapled haemorrhoidopexy is an effective
      treatment for haemorrhoids and is a significantly less painful operation. Any
      postoperative bleeding that may occur is easy to resolve and its incidence
      depends on the careful haemostatic control at the staple line. The new PPH 03
      stapler device seems to be more effective than the PPH 01 device for control of
      the staple line suture. We would suggest that colorectal surgeons who are
      familiar with the technique and aware of possible complications should perform
      stapled haemorrhoidopexy using the PPH 03 stapler.

PMID- 17500180
TI  - [Transfixed stitches technique versus open haemorrhoidectomy. Results of a
      randomised trial].
AB  - Nowadays different surgical techniques are available for the treatment of
      haemorrhoids even if a general, international consensus is still lacking. The
      authors, through a personal interpretation of haemorrhoids based on the PATE 2000
      Sorrento classification, report on a comparative trial of haemorrhoidectomy by
      the transfixed stitches technique versus an open surgical technique (Milligan
      Morgan). Particular attention was devoted in this prospective randomised trial to
      analysing the early postoperative side effects (bleeding, urinary retention), the
      time taken to return to active life and wound healing. Patients with grade III-IV
      haemorrhoids were enrolled in our study and divided into two groups: one treated
      by the transfixed stitches technique and the other by the Milligan-Morgan
      procedure. The main outcome measures such as analgesic use during the first week,
      early side effects, wound healing and the time taken to return to active life
      were evaluated. Patients were followed for 6 months after surgery. A total of 160
      patients were enrolled, 80 in each group. The pain score after surgery was
      significantly lower in the transfixed stitches group than in the Milligan-Morgan
      group (p < 0.01). 30% of the transfixed stitches patients took analgesics in
      comparison with 90% of the Milligan-Morgan patients (p < 0.01). Postoperative
      pain after the start of bowel movements in the transfixed stitches group was
      lower than in the Milligan-Morgan group. Wound healing was immediate in the
      transfixed stitches patients and was obtained after one month in the open surgery
      group. Haemorrhoidectomy by the transfixed stitches technique is more
      advantageous in comparison with the Milligan-Morgan procedure because of its
      lesser discomfort for the patient, earlier wound healing, milder side effects,
      shorter surgical time and earlier return to active life.

PMID- 17500181
TI  - [Transcutaneous excision of the submandibular and sublingual glands: notes on
      anatomy and surgical technique].
AB  - Removal of the submandibular and sublingual glands requires in-depth knowledge of
      the anatomy and scrupulous technique for the purposes of limiting the functional
      and aesthetic damage, which is unjustifiable above all in the treatment of benign
      lesions (sialodenitis, lithiasis). After presenting the main aspects of the
      surgical anatomy of the submandibular space, the operative technique for its
      dissection with removal of the submandibular gland and excision of the sublingual
      gland is described. The complexity of the anatomical structures that may be
      involved in submandibular and sublingual gland lesions is the cause of
      unsatisfactory functional and aesthetic outcomes in some cases. The most feared
      complications are lesions to nerve formations, due both to the resulting deficits
      and the possible legal implications.

PMID- 17500182
TI  - [Preoperative diagnosis of incidental carcinoma in multinodular goitre by means
      of electromagnetic interactions].
AB  - In the evaluation of multinodular goitre, finding a malignant neoplasia is often
      an unexpected result of the histological diagnosis. TRIMprob (Tissue Resonance
      Interaction Method Probe) is a portable system for non-invasive diagnosis, that
      utilises the different electromagnetic properties of healthy and pathological
      tissues, producing a low-power magnetic field that interacts with the molecular
      structure of tissues. The interference levels are detected by a receiver device
      and are elaborated with software in a graph consisting of 3 easily interpretable
      bands. The objective of our study was to assess the usefulness of the TRIMprob
      system in the preoperative diagnosis of carcinoma in patients with multinodular
      goitre. Over the period from January 2005 to March 2006 we used TRIMprob to
      screen 51 patients with a clinical diagnosis of multinodular goitre, later
      operated on by total thyroidectomy. We then compared the TRIMprob response with
      the histological diagnosis on the surgical specimen. The TRIMprob results
      suggested 46 cases compatible with non-malignant goitre and 5 suspected cancers.
      The final histological diagnosis confirmed these results with 46 cases of
      multinodular goitre and 5 papillary carcinomas. The sensitivity, specificity and
      diagnostic accuracy of the procedure were all 100%. On the basis of these
      preliminary results, TRIMprob seems to be a highly accurate method for the
      detection of suspected carcinomas in the context of multinodular goitre. If these
      results are confirmed, new prospects could be opened up in the diagnosis of
      thyroid diseases.

PMID- 17500183
TI  - Hamartochondroma arising from a tracheal bronchus.
AB  - Tracheal bronchus is a congenital abnormality rarely described in the literature.
      It is mostly completely asymptomatic. This condition may rarely be associated
      with inflammatory diseases. Exceptional are those cases in which the condition is
      associated with malignancy. We describe a case of a 45-year-old man in whom a 3
      month history of non-productive cough and chest pain led to a diagnosis of a
      solitary pulmonary nodule associated with a tracheal bronchus. The
      histopathological examination after VATS enucleation showed the presence of a
      hamartochondroma. To the best of our knowledge this is the first case in which a
      hamartochondroma has been found to be associated with a tracheal bronchus.

PMID- 17500184
TI  - Synchronous nephrectomy and right hepatectomy for metastatic chromophobe renal
      cell carcinoma: report of a case and review of the literature.
AB  - The prognosis of metastatic renal cell carcinoma is poor, since non-operative
      modalities for advanced renal carcinoma have failed to yield effective results.
      In fact, there is no indication for radiotherapy, except for palliative treatment
      of symptomatic bone metastases, and systemic chemotherapy is not effective.
      Despite the promising early results with immunotherapy, a complete response
      occurs in less than 15% of patients and is rarely lasting. Surgery, when
      indicated, seems to be the only therapeutic option possible. Liver metastases
      occur in 20% of cases and are often multiple. Experience with hepatectomy for
      metastatic renal tumours has rarely been reported. Not only does a small group of
      patients have isolated liver metastases that may be treated with radical surgery,
      but also extrahepatic metastases ordinarily coexist at the time of diagnosis. We
      report a case of a 55-year-old man with a chromophobe renal cell carcinoma with a
      single synchronous hepatic metastasis that were treated simultaneously with
      radical nephrectomy and right hepatectomy. To the best of our knowledge this is
      the first case of a single metastasis of a chromophobe renal cell carcinoma
      treated with synchronous kidney and hepatic resection.

PMID- 17500185
TI  - [Thyroid hemiagenesis associated with Flajani's disease and papillary carcinoma.
      A case report].
AB  - Non-development of a thyroid lobe is a rare abnormality. The condition is
      normally diagnosed incidentally in the course of investigations performed for the
      coexistence of pathological conditions and/or functional disorders of the gland.
      We report a case of thyroid hemiagenesis in a patient suffering from Flajani's
      disease whom we submitted to total thyroidectomy due to the simultaneous presence
      of a papillary carcinoma. In the context of a condition such as thyroid
      hemiagenesis which is in itself a rare occurrence, there are very few reports of
      cases in which the dysgenesis is associated with Flajani's disease. The
      coexistence of thyroid hemiagenesis, Flajani's disease and papillary carcinoma is
      truly exceptional and has never been reported in the literature.

PMID- 17500186
TI  - [The primary prevention of the cardiovascular disease begins in the infancy].

PMID- 17500187
TI  - [Sequential segmental analysis in 100 cardiopulmonary specimens].
AB  - OBJECTIVE: To evaluate the feasibility and accuracy of the sequential segmental
      analysis (SSA) to diagnose congenital heart diseases. MATERIAL AND METHODS: 100
      cardiopulmonar specimens were analyzed according with the sequential segmental
      analysis. The atrial situs, atrioventricular (AVC) and ventriculoarterial
      connections (VAC) were defined, finally associated lesions were observed.
      RESULTS: From 100 specimens, 91 had situs solitus (SS), 6 inversus (SI) and 3
      isomerism (2 right isomerism and 1 left isomerism). The AVC in these hearts were:
      89 biventricular, 80 (90%) concordant, 6 (6.7%) discordant and 3 (3.3%) ambiguous
      (2 right topology an 1 left topology). The univentricular AVC were 11, 4 (36%)
      had absent left AVC (mitral atresia), 3 (27%) absent right AVC (tricuspid
      atresia), 2 (18%) double inlet right ventricle (DIRV), 1 double inlet left
      ventricle (DILV) and 1 (9%) double inlet undetermined ventricle. The VAC in SS
      were: 52 (57%) concordant, 13 (14%) discordant, 6 (6.6%) double outlet right
      ventricle (DORV), 20 (22%) with single outlet (13 pulmonary atresia , 5 aortic
      atresia and 2 common arterial trunk). The VAC in SI were: concordant in one,
      (16.7%), discordant 3 (50%) and DORV in 2 (33.3%). In the hearts with isomerism,
      the VAC were concordant in one, DORV in one and single outlet in another
      (pulmonary atresia). The associated anomalies were ASD (67%), PAD (51%) and VSD
      (53%). CONCLUSIONS: The SSA was and effective and accurate tool to codify clear
      and completely the congenital heart disease. It is suggested that if the SSA is
      normal to describe this situation as a Normal Basic Heart Organization and then
      to describe the associated anomalies.

PMID- 17500188
TI  - [High-density lipoproteins (HDL) size and composition are modified in the rat by
      a diet supplemented with "Hass" avocado (Persea americana Miller)].
AB  - PURPOSE: To determine the effects of dietary avocado on HDL structure and their
      associated enzyme, paraoxonase 1 (PON1). METHODS: Fifteen Wistar male rats
      received avocado as part of their daily meal (5 g by 17.5 g chow diet), keeping
      the caloric intake similar to the control group (n=15) that received their usual
      chow diet. After 5 weeks, HDL were isolated by sequential ultracentrifugation and
      their size and chemical composition were analyzed. PON1 was determined in serum
      spectrophotometrically using phenylacetate as substrate. RESULTS: Rats that
      received avocado had about 27% lower triglycerides plasma levels whereas their
      HDL-cholesterol was 17% higher as compared to control group. The mean HDL Stokes
      diameter was significantly lower in avocado group (11.71 +/- 0.8 vs. 12.27 +/-
      0.26 nm, in control group, p < 0.05). The HDL size decrease was associated to a
      lower content of protein, particularly of apo Al, with a concomitant higher
      proportion of phospholipids in HDL isolated from avocado group. HDL structural
      modifications induced by avocado were not related to modifications of LCAT and
      PLTP activities, but occurred in parallel with higher serum levels of PON1
      activity when compared to the controls (57.4 +/- 8.9 vs. 43.0 +/- 5.6
      micromol/min/mL serum, p < 0.05). CONCLUSIONS: The inclusion of avocado in the
      diet decreased plasma triglycerides, increased HDL-cholesterol plasma levels and
      modified HDL structure. The latter effect may enhance the antiatherogenic
      properties of HDL since PON1 activity also increased as a consequence of avocado.

PMID- 17500189
TI  - [Myocardial revascularization in the female population].
AB  - OBJECTIVES: To analyze the factors that influence outcomes of surgical myocardial
      revascularization in the female population. PATIENTS AND METHOD: This is a
      retrospective study in which 128 woman, subjected to GABC[IBM1] from January to
      September 2004, were enrolled in an univariate and multivariate analysis of risk
      factors associated with morbidity and mortality. RESULTS: The mean age was 69.19
      +/- 9.05 [IBM2] years, the most frequent pathologies, comorbilities, were
      dyslipemia, hypertension, and myocardial infarction. Unestable angina was found
      in 63.28% patients and stenosis in the left main coronary artery 42.96%; NYHA III
      IV in 23.43%. The EuroSCORE mean preoperative risk was [IBM3] 5.57. Twelve
      surgeries were emergencies. Mean of grafts was 2.57. Mortality corresponded to
      5.4% in programmed surgeries, 7% global. Univariate analysis identified this risk
      factors releated to mortality (p < 0.05): age older than 67 years, NYHA III-IV
      and emergency surgery, complicated in 25.2%. Follow-up was kept in 90.8% of
      patients, mean follow-up time was 17.11 (+/- 14.94) months; 115 patients did not
      present angina. The risk factor for angina during follow-up, in the univariate
      analysis (p < 0.05) was not having used the left internal thoracic artery as
      graft for the anastomosis of the anterior descending artery. CONCLUSIONS:
      Emergency surgery, age older than 67 years, and NYHA III-IV, were independent
      risk factors associated with mortality in this group. The use of artery grafts
      associated to reduced angina during follow-up.

PMID- 17500190
TI  - [Morbidity and mortality by ischemic heart disease and stroke in Mexico. 2005].
AB  - Cardiovascular diseases are the main cause of death and disability in Mexico. 25%
      of deaths under 60 years of age are related to chronic degenerative diseases.
      These disorders are more common in developing countries and are caused by an
      excessive intake of fatty acids, sodium, alcohol, tobacco consumption and
      decrease in physical activity. The prevalence of risk factors is increasing not
      only in adult population but also in youth and children. Data from the Department
      of Epidemiology from the Mexican Ministry of Health in the period between 1998
      and 2000 showed that the death caused by coronary artery disease was more
      frequent in men (55%) than women (45%) and acute coronary syndrome was
      responsible for deaths in 83.5% of men and 76.8% in women. Primary Prevention
      Programs are necessary to decrease the impact of cardiovascular diseases.

PMID- 17500191
TI  - [Does the Tako-Tsubo syndrome need a certain coronary anatomy in the apical
      ventricular region as predisposing factor?].
AB  - The Tako-Tsubo transient left ventricular apical ballooning was born as a
      clinical profile in the year 2001. This syndrome occurs mainly in women older
      than 60 years and it is frequently preceded by a physical or emotional stress.
      Its presentation simulates a myocardial infarction, although with some
      differences: the pain is not always typical, and its intensity is moderate. The
      electrocardiogram reveals an elevation of ST in the anterior face in 90% of the
      cases; from the second day on, negative T waves in V2 through V6 leads are
      present, along with prolongation of the QTc interval. Enzymes are poorly elevated
      as expected from the electrical alterations. The alteration that defines the
      syndrome is the hypokinesis or akinesis of the apical segments with hyperkinesis
      of the basal ones. The main uncertainty of the Tako-Tsubo syndrome is its
      pathogenesis, its elucidation will provide advances in the practical handling of
      this syndrome2. We present the clinical case of a patient with this syndrome and
      a review of the existing medical literature on the possible association with a
      predisposing coronary anatomy in the apical segment.

PMID- 17500192
TI  - [Massive pulmonary embolism, thrombus in transit, and right ventricular
      dysfunction].
AB  - Massive pulmonary embolism is associated with an increased mortality. It is
      secondary to migration of a venous thrombus to the right atrium or ventricle
      (thrombus in transit) towards the pulmonary circulation. The hemodynamic
      performance depends on the baseline cardiopulmonary status of the patient and the
      extent of obstruction. Right ventricular dysfunction will appear as a direct
      consequence of a major obstruction and hemodynamic collapse. The treatment of
      choice is thrombolysis, either intravenous in a peripheral vein, or local
      administration associated with percutaneous thrombus fragmentation or surgical
      embolectomy. We present the clinic case of a woman with massive pulmonary
      embolism. The transthoracic echocardiogram showed the presence of three auricular
      thrombus, right ventricular dysfunction and pulmonary hypertension. A right side
      catheterization and angiography demonstrated the pulmonary artery obstruction and
      right ventricular dysfunction. The troponin-I was elevated as a result of right
      ventricular strain. Mechanical thrombectomy was made using a pigtail catheter and
      thrombolysis into the pulmonary artery using recombinant tisular plasminogen
      activator. There was an immediate hemodynamic improvement and the post
      thrombolysis angiography performed after 24-h demonstrated an improvement of the
      pulmonary circulation as well as decreased pulmonary artery pressures.

PMID- 17500193
TI  - [Angioplasty guidewire entrapment affer stent implantation: report of two cases
      and review of the literature].
AB  - Angioplasty guidewire entrapment, with or without retention of a fractured
      segment, is an infrequent complication and may lead to acute coronary ischemia
      due to thromboembolic occlusion. Management can be surgical, conservative or
      percutaneous. We describe two patients in whom the guidewire remained entrapped
      with the stent during the pullback maneuver after successful stent implantation.
      In one patient, we managed to extricate a metallic guidewire using the balloon as
      a wedge. In the other patient, a fragment of the non-metallic guidewire tip, with
      hydrophilic coating, remained trapped after being "cut" by the stent during
      traction towards the ostium while attempting removal. The retained segment was
      isolated from the blood stream by implanting a synthetic coronary stent graft. We
      emphasize the high risk of "cutting" this type of non-metallic guidewire in case
      of engagement with the stent, and we review the literature of this rare
      complication.

PMID- 17500194
TI  - [C-reactive protein: cardiovascular issues of an acute-phase protein].
AB  - C-reactive protein (CRP) is a nonspecific acute phase protein that has been used
      as an inflammatory marker for decades. More recently, it has been proposed as a
      predictor of cardiovascular disease (myocardial infarction, stroke, peripheral
      artery disease and sudden heart death). Physiologic functions of CRP as an anti
      inflammatory scavenger molecule have begun to emerge. CRP binds to damaged
      lipoproteins and facilitates their removal by phagocytes, partially activating
      the complement cascade. Increased levels of CRP may result in direct effects on
      vascular cells, including the induction of cytokines and prothrombotic factors.
      Although previous studies suggested a potent independent association of CRP
      levels with cardiac events, the strength of this association has been shown to be
      weaker than previously reported in a recent large meta-analysis and in
      prospective studies. Therapy with statins in patients with coronary artery
      disease has been found to reduce adverse outcomes in association with reductions
      of CRP levels, independently of their effects on the lipid profile.

PMID- 17500195
TI  - [Electrical manifestations of dead myocardium associated to proximal blocks of
      intermediate degree].
AB  - The electrical manifestation of dead myocardium associated to incomplete bundle
      branch block, i.e., with a limited "jumping wave" phenomenon, are exposed. Our
      description is based on previous experimental studies and validated by electro
      anatomical comparisons. In previous experimental reports, the electrical
      manifestations of dead myocardium in the presence of varying degrees of
      associated block have also been described. The main electrocardiographic changes
      are related to the location and extent of damaged region and to degree of bundle
      branch block. If a left bundle branch block coexists with dead myocardium, small
      Q waves are registered in left unipolar leads exploring the damaged area. In
      these leads, the signs of subepicardial or transmural injury are increased. When
      a right proximal block coexists, the main changes concern the morphologies
      registered in the unipolar right epicardial and precordial leads. The electrical
      changes are due to the spatial orientation of the electromotive forces of
      ventricular depolarization and repolarization. The electrocardiographic changes
      described here can be satisfactorily understood in the light of the present
      knowledge on the ventricular electrical phenomenon.

PMID- 17500196
TI  - [Effect of enalapril on endotheliun-dependent contractile reactions and oxygen
      cost of work of the smooth muscles in experimental diabetes mellitus].
AB  - The influence of angiotensin-converting enzyme on endotheliun-dependent
      contractile vascular reactions was investigated on the rat model of
      streptozotocin-induced diabetes mellitus. It is shown, that the long-term
      administration of enalapril results in partial restoration of disturbed at
      diabetes mellitus reactions and also to reduction of oxygen cost of smooth
      muscles and myocardial work. Thus, after 28-day's of oral administration of this
      drug the restoration of endotheliun-dependent dilatation of aorta and coronary
      vessels, increase of stretch-induced contractile responses of vascular smooth
      muscles, reduction of stiffness of isolated portal vein strips are observed.
      Possible mechanisms of such changes are following: increase of nitric oxide
      synthesis (at the expense of constitutive NOS activity) and reduction of
      oxidative stress, to what the decrease of diene conjugates contents in tissues of
      animals with diabetes mellitus after long introduction of enalapril testifies.

PMID- 17500197
TI  - [The role of the ovarian steroid aromatase in pathogenesis of reproductive cycles
      disorders].
AB  - In the rats with regular estrous cycles effects of letrozole, a steroid aromatase
      inhibitor, on the enzyme activity in ovarian tissues and reproductive system
      condition were studied. Letrozole was administered per os daily in a dose of 1
      mg/kg b.w. over 10 days. As the result of treatment, 20.5-fold decrease in
      aromatase activity was obtained. All animals have developed persistent anestrus
      with vaginal smear patterns being similar to diestrus. Uterine weights were two
      fold less than that of controls, and ovarian weights increased by one third. The
      ovaries contained multiple cystoidal follicles. Results of the study demonstrate
      the key role of ovarian steroid aromatase in letrozole-induced disorders of
      reproductive cycles. Letrozole might be recommended for experimental modeling of
      reproductive cycle disorders in female rats.

PMID- 17500198
TI  - [Characteristics of neuronal activity in nucleus accumbens in spontaneously
      hypertensive rats].
AB  - Spontaneously hypertensive rats (SHR) are generally considered as genetic model
      both for essential hypertension and attention-deficit hyperactivity syndrome.
      Neuroanatomical substrates and mechanisms of neural disorders in the SHR have not
      been elucidated. This study aimed to determine if the background impulse activity
      of Nucleus accumbens, core (NAc) neurons and their reactions evoked by amigdala
      stimulation in the SHR differ from those of normotensive Wistar rats (WR).
      Besides that we investigated the influence of microiontophoretic beta-adrenergic
      receptors agonist isoproterenol administration (5 mM solution; pH 5.0; 10-30 nA)
      on the NAc neuronal activity. Single unit extracellular recordings were performed
      under urethane anesthesia. These results showed that percentage of the NAc
      neurons with bursting discharge pattern of the background impulse activity is
      significantly (P < 0.001) greater in SHR (42%) compared to WR (13%). Also, more
      of the NAc neurons in the SHR (27% had cyclic fluctuations of the frequency of
      background activity with second period than in the WR (4%). Excitatory reactions
      of the NAc neurons evoked by amigdala stimulation in the SHR had more long
      duration. Activation of beta-adrenergic receptors under isoproterenol
      administration allows us to reproduce a burst type of neuronal impulsation and
      cyclic fluctuations of the NAc background neuronal activity in both kinds of
      animals. Findings obtained support the possibility that in the SHR beta
      adrenergic function within the NAc is enhanced compare to control.

PMID- 17500199
TI  - [Transfer factor of immune reactivity to diphtheria-tetanus anatoxin modulates
      the action of neurotransmitters in the intestinal smooth muscle].
AB  - Transfer factor (TF) of immune reactivity (10(-5) - 10(-3) mg/ml) to diphtheria
      tetanus anatoxin modulates slow waves and spontaneous contractile activity of non
      atropinized smooth muscle stripes (SMS) of guinea-pig taenia coli. TF (10(-4)
      mg/ml) transforms slow waves into stable depolarization and tonic contraction.
      After SMS atropinization, the substance acts in the same way. In the presence of
      methylene blue (10(-5) M), a guanylatecyclase blocker, FT induces transitory
      increase of SMS muscle tone, which is followed by their stable relaxation. ATP
      and UTP, purinoceptors agonists, evoke substantial hyperpolarization of smooth
      muscle cells membrane and their relaxation. FT enhances post-inhibitory
      excitation in SMS. In the presence of acetylcholine (10(-5) M) FT (10(-4) mg/ml)
      transforms the inhibitory ATP action on tonic contraction into excitative. This
      substance (10(-5), 10(-4) mg/ml) enhances Ca2+ mobilization from ryanodine
      sensitive calcium store, inhibits the release of these cations from IP3-sensitive
      calcium store of sarcoplasmic reticulum. TF demolishes the inhibitory actions of
      sodium nitroprusside (nitric oxide donor), and noradrenaline in taenia coli
      smooth muscles.

PMID- 17500200
TI  - [Effect of intermitent hypoxia on ultrastructure and prooxidant-antioxidant
      balance in the soft tissue of the periodontium in acute immobilization stress].
AB  - The changes of prooxidant-antioxidant balance and morphofunctional state of soft
      tissue of paradontum under the acute immobilization stress, intermittent hypoxia
      and its complex influence were investigated. It was shown, that intermittent
      hypoxia can stimulate own endogenous mechanisms of nonspecific resistance, such
      as antioxidant protection in soft tissue of paradontum. Normalization of the
      prooxidant-antioxidant balance under immobilization stress after intermittent
      hypoxia essentially improved the morphofunctional state of tissue investigated
      with decrease of edema and improvement of mitochondria apparatus ultrastructure.

PMID- 17500201
TI  - [Effects of experimental muscle pain on short and long-latency components of
      stretch-reflex in the elbow muscles of the unanaesthetized cat].
AB  - Electromyographic (EMG) activity of the elbow joint muscles induced during
      passive extension of the joint was recorded from the unaesthetized cat before and
      after injection of 5% NaCl solution which has been used as an activator of
      nociceptors. It was shown that the amplitude of the long-latency M2 component of
      flexor stretch-reflex was significantly increased after injection of saline while
      the amplitude change of shot-latency M1 component was insignificant. The latency
      of EMG in flexor significantly decreased. The changes of extensor EMG response
      parameters were similar but less expressed. Duration of such effect could achieve
      20 minutes, after that all response parameters of stretch-reflex returned to the
      standard values.

PMID- 17500202
TI  - [The weak acids as proton carriers through bilayer lipid membranes].
AB  - The ability of the weak inorganic acids (H2S, HCN) and lower carboxylic acids to
      interact with bilayer lipid membranes (BLMs), change their conductivity, act as
      the protonophores were investigated. The mechanism of the BLM conductivity change
      was studied. The factors affecting the acids interaction with model lipid
      membranes were determined. Maximum conductivity change observes at pH equal
      dissociation constant of weak acids and depends on the distribution coefficient
      "octanol(membrane)-water".

PMID- 17500203
TI  - [Characteristics of passive Ca2+ -transport from cells of the myometrium
      sarcoplasmic reticulum in rats].
AB  - With use of model ofpermeabilizated myocytes from rat uterus and 45Ca2+ it is
      shown, that passive Ca2+ transport from sarcoplasmic reticulum (cation has been
      preliminary accumulated in ATP-dependent process) is sensitive to 2 mM caffeine,
      0,1 mM lidocaine, and also to exogenous Ca2+ (it was activated at increase in
      concentration Ca2+ from 10(-7) up to 10(-4) M and was suppressed at 10(-3)) and
      pH level (was stimulated by alkalization of medium), along with significant
      suppression of Mg2+ (0.2 - 4 mM). The analysis of the results received allows us
      to assume that the model used by us is adequate for studying processes of Ca2+
      release from sarcoplasmic reticulum, mediated by ryanodine receptor channels.

PMID- 17500204
TI  - [Mesenchymal progenitor cells. Biological characteristic and prospects for their
      use].
AB  - Imunophenotic characteristic of the mesenchymal stem and progenitor cells, their
      tissue origin and functional peculiarities as well as immunological aspects of
      its transplantation are presented in the article. Also the address migration and
      the site-specific differentiation of mesenchymal stem cells its age-related and
      pathological process induced changes are discussed. Prospects of clinical use of
      mesenchymal stem cells for the treatment of degenerative arthritis, spinal cord
      injuries, myocardial infarction and other disorders are shown.

PMID- 17500205
TI  - [Intracellular determinants of calcium signaling].
AB  - The review describes the mechanisms of function and regulation of store-operated
      (so called SOC) channels and their connections with different intracellular
      calcium regulating structures. The function of both ryanodine sensitive and
      inisitol-1,3-phosphate sensitive endoplasmic reticulum are presented. The
      mechanisms of their connections with mitochondria and potential-activated
      channels are shown. Main attention is concentrated on compensatory calcium entry
      (CCE) connected with depletion of endoplasmic reticulum, the role of different
      transient receptor potential (TRP) channels in this process and possible
      mechanisms of their activation.

PMID- 17500206
TI  - [The maturation of the spermatozoa: events, consequences and possible ways of
      control].
AB  - Maturation of spermatozoa represents a formation of competent cell with capacity
      to fertilize. For the purpose of this review the morphological and functional
      changes of nucleus, plasmatic and nuclear membranes, tail region as well as the
      change of localisation and activity of enzymes have been described to illustrate
      the epididymis stage of maturation. Particular attention has been paid to the
      role of active oxygen species in the cell transformation, pro- and antioxidant
      balance during the maturation and to the systems controlling gametes control. The
      possible ways of influence on the some events of spermatozoa maturation are
      shown.

PMID- 17500207
TI  - [The molecular-genetic aspects of differentiation of schizoaffective psychosis
      and attack-like progressive schizophrenia].
AB  - To clarify nosologic differences between schizoaffective psychosis (SAP) and
      attack-like progressive schizophrenia at molecular-genetic level, the genetic
      polymorphism of serotonin receptor type 2A (5HTR2A), serotonin transporter (5
      HTTLRP), and brain-derived neurotrophic factor (BDNF) was studied in 563 patients
      with schizophrenia (mean age 37.7+/-14.4 years, age at disease onset 26.7+/-11.4
      years), and 171 patients with SAP (mean age 30.7+/-11.6 years, age at disease
      onset 24.9+/-8.5 years). The control group consisted of 536 psychiatrically well
      subjects. Clinical symptoms and personal features were evaluated as well. By
      comparison with schizophrenic patients, those with SAP were featured by subtle
      negative symptoms and personality changes that supported the evidence that SAP is
      a disorder with a favorable outcome. Molecular-genetic studies revealed higher
      frequencies of S allele and SS genotype (5-HTTLPR polymorphism), which are
      thought to be associated with depression and depressive symptoms, and higher
      frequency of BDNF genotypes, containing Met allele, in combination with 5-HTTLRP
      genotypes containing L allele, in patients with SAP as compared to the
      schizophrenic group. C allele and CC genotype (T102C 5-HTR2A polymorphism)
      frequencies were higher in both groups of patients vs. controls. In conclusion,
      the results confirm the concept considering SAP an independent nosologic
      category.

PMID- 17500208
TI  - [Abnormal patterns of cortical synaptic connectivity in schizophrenia].
AB  - Electron microscopic morphometric study of postmortem prefrontal cortex (area 10)
      and visual cortex (area 17) was performed to estimate the numeric density (Nv) of
      synapses in layers I and II, neurons in layer II and the number of synapses per
      neuron in layer II in 20 cases of chronic schizophrenia and 16 healthy controls
      using stereological physical dissector method. In the prefrontal cortex the Nv of
      axospinous synapses was significantly lower in layer I (-20%, p < 0.05) in
      schizophrenia group and in the subgroup with predominantly positive symptoms as
      compared to controls (p < 0.05). On the contrary, a significantly higher Nv of
      synapses (+24%, p < 0.05) and the number of synapses per neuron were found in
      layer II (+42%, p < 0.05) in schizophrenia group and in the subgroups of cases
      with predominantly negative symptoms and a continuous course of schizophrenia (p
      < 0.001) as compared to the control group. The subgroup of cases with
      predominantly negative symptoms displayed a significantly lower number of neurons
      in layer II of the prefrontal cortex compared to controls (p < 0.05) and the
      subgroup of cases with predominantly positive symptoms (p < 0.01). In the visual
      cortex the number of axodendritic synapses per neuron in layer II was
      significantly higher in schizophrenia, but the other parameters did not differ
      from those in the control group. These prominent abnormalities of synaptic
      connectivity might be the structural basis for altered cognitive functions
      associated with changes in intracortical, cortico-cortical, and cortico
      subcortical pathways, and could contribute to the formation of positive and
      negative symptoms and altered neuronal plasticity in patients with schizophrenia.

PMID- 17500209
TI  - [The influence of atypical neuroleptics on the immune system of patients with
      schizophrenia].
AB  - Humoral and cellular immunological parameters were studied in 59 schizophrenic
      patients and 38 healthy subjects. It was demonstrated that high level of
      circulating immune complexes is characteristic of the acute state (a relapse) of
      schizophrenia. The level of this parameter was higher in patients before
      treatment vs. healthy controls; after therapy with olanzapine this level
      decreased and did not differ from that of controls. The functional activity of
      immunocompetent cells (the phagocyte activity of neutrophiles and monocytes, the
      cytotoxic activity of natural killer lymphocytes, interleukin-2, and interleukin
      10 production) did not depend on the clinical condition of the patients and the
      therapy and was significantly lower than that of controls both before and during
      the treatment. Attention should be paid to the fact that the level of IL-1beta
      production in schizophrenia patients did not differ from that of controls. After
      eight weeks of therapy the level of IL-1beta production increased significantly
      in all groups of patients and was significantly higher than that of controls
      during the whole observation period irrespectively of sex and patients' response
      to the therapy.

PMID- 17500210
TI  - [Glutamate dysmetabolism in patients with schizophrenia].
AB  - The glutamate-ergic hypothesis of schizophrenia pathogenesis has been
      substantially expanded due to recent data on changes in glutamate metabolizing
      enzymes (GME) in the brain of patients with schizophrenia. Significant changes in
      the amounts of glutamate synthetase (GS), glutamate synthetase-like protein
      (GSLP), and glutamate dehydrogenase (GDH) have been found. Alterations in the
      cerebral metabolism of glutamate (together with disturbances in glutamate
      receptors and transporters) apparently play an important role in the pathogenesis
      of schizophrenia. Glutamate dysmetabolism has been shown to be of systemic
      nature, i.e. the amounts of GME (GDH and GSLP) are elevated in platelets of
      patients with chronic schizophrenia, and these enzymes may be vital markers of
      glutamate system status. The amounts of GDH and GSLP were monitored in platelets
      of chronic patients during treatment with olanzapine, an atypical neuroleptic
      modulating glutamate concentration in the brain and blood of patients. GSLP
      amount can serve as a predictor of the duration of treatment to achieve a
      positive outcome. Further studies of GME in blood may result in elaboration of
      prognostically valuable biological tests not only for schizophrenia treatments,
      but also for other mental and nervous system diseases in which the glutamate
      system is substantially implicated.

PMID- 17500211
TI  - [Biological mechanisms of the individual variability of the anxiolytic action of
      opioids].
AB  - The opioid system is one in a number of peptidergic regulatory systems that
      support an appropriate anxiety level. The drugs that interact with the opioid
      system have been shown to influence anxiety, although there is a notable
      variability in their pharmacological effects. Biological mechanisms of this
      variability are considered to be the heterogeneity of opioid receptors, the ratio
      of the processes of their expression and desensitization, and the balance between
      the synthesis and degradation of endogenous opioid peptides. For instance, the
      anxiolythic effect of the synthetic derivate of enkephalin in rats was detected
      after stress-induced exhaustion of endogenous opioids, and its efficacy depended
      on the degree of delta- and mu-opioid receptor desensitization in some brain
      regions. The anxiolythic properties of the heptapeptide Selanc that has also been
      shown to affect the opioid system are most prominent in subjects with elevated
      activity of enzymes degrading endogenous opioid peptides. Thus, delicate
      correction of the opioid system with drugs of peptide nature is supposed to
      become a new approach to treatment of some forms of anxiety disorders accompanied
      with exhaustion of the endogenous opioid system and, in particular, of
      generalized anxiety disorder.

PMID- 17500212
TI  - [Regulatory peptides and psychomotor development in infants].
AB  - Regulatory peptides (RP) are an important homeostatic factor. The maternal
      organism and placenta are substantial sources of RP for fetus during the prenatal
      period. Not only endogenous, but also exogenous RP play an important role during
      early postnatal period. In this study, the concentration of exogenous RP
      (casomorphins-7) and the activity of peptidases (enkephalinases) in the serum of
      breastfed and bottle-fed infants were estimated. Possible interrelation between
      these two parameters and the psychomotor development (PMD) of infants were
      evaluated. Using specially developed RIA, the investigators estimated the
      presence of human and bovine casomorphins immunoreactivity (CMir) in the serum of
      breastfed and bottle-fed infants. A distinct correlation of CMir with PMD was
      demonstrated. The activity of RP-degrading serum enzymes also correlated with PMD
      level. The role of endo- and exogenous peptides in normal PMD process and in the
      pathogenesis of early child autism is discussed in the article.

PMID- 17500213
TI  - [Individual heart functioning variability under exposure to equal physical
      factors in patients with different vegetative system tone].
AB  - The article describes changes in heart rhythm variability (HRV) as a response to
      equal complex physical factors (hyperthermia of 60 degrees C with low relative
      humidity of 8 to 15%, air ionization, thalasso, and relaxing music). The subjects
      of the study were 28 individuals having no verified chronic diseases, who
      underwent a course of five recovery procedures using exposure to a complex of
      weak physical factors realized in Ionic House technology (Japan). The study found
      that changes in heart functioning as a response to equal physical factors
      depended on the initial vegetative system tone. Patients with normotonic and
      sympathicotonic heart regulation displayed the activation of parasympathetic
      vegetative nervous system as a result of a single exposure to a complex of
      physical factors, whereas in vagotonic patients sympathetic heart regulation was
      activated under the same conditions.

PMID- 17500214
TI  - [The allelic polymorhism of IL-1alpha and IL-beta genes in patients with chronic
      inflammatory periodontal diseases].
AB  - The researchers studied the polymorphism of IL-1alpha and Il-beta genes in
      patients of different ages with severe chronic generalized periodontitis and
      people with healthy periodontium. They used molecular and genetic techniques such
      as polymerase chain reaction and reverse hybridization with Geno Type PRT
      reagents (Germany). The study demonstrated a correlation between high frequency
      of genetic polymorphism in IL-1A -899 and IL-1B +3953 loci and the development of
      severe periodontitis in patients less than 35 years of age, and a possibility of
      using this parameter in complex assessment of patients with periodontal diseases.
      The research suggests that Geno TypeR PRT test system should be recommended for
      evaluation of patients with a high risk of aggressive periodontal diseases, as
      well as patients with therapy-resistant periodontitis.

PMID- 17500215
TI  - [Comparative immunophenotypic characterization of human and monkey permanent
      lymphoid culture cells].
AB  - The aim of the study was to define the comparative immunophenotypic
      characteristics ofwidely spread lymphoid cell cultures, derived from Burkett's
      lymphoma named as Raji and P3HR-1 in comparison with analogous monkey cultures.
      It has been shown that P3HR-1 culture consists of similar type cells - activated
      B-lymphocytes CD23 with k phenotype, which demonstrates its monoclonality. Raji
      culture includes cells with markers of immature B-lymphocytes CD10 and CD24, as
      well as elements expressing CD10 antigens. T-cell markers were found in none of
      the cultures. In contrast to human cells, monkey lymphoid culture expressed both
      B- and T-cell markers. Moreover, in one of them, obtained from a green monkey, T
      cells of suppressor type (CD8) prevailed. The immunophenotypic characteristics of
      primate lymphoid cell cultures, revealed by the study, are of great importance
      for their proper application to medical and biological studies.

PMID- 17500216
TI  - [Clinical and laboratory aspects of the phenomenon of macroprolactinemia].
AB  - The question of the clinical importance of high-molecular prolactin forms is
      stressed in modern scientific literature on the problem of hyperprolactinemia.
      About 25% of all cases of hyperprolactinemia have been associated with the
      phenomenon of macroprolactinemia. This is most typical of patients with mild or
      moderate increase in prolactin level. There is no consensus on the therapeutic
      tactics in these patients. It should be discussed whether macroprolactin
      measurements should be done in all cases of high total prolactin level in order
      to prevent hyperdiagnostics and unnecessary additional laboratory tests and
      therapeutic intervention.

PMID- 17500217
TI  - [Influence of environmental factors on respiratory organs].

PMID- 17500218
TI  - [Trends of tuberculosis morbidity and mortality in Russia in 2005].
AB  - The most informative indices; such as tuberculosis morbidity and mortality, were
      used to assess the tuberculosis epidemiological situation in Russia in 2005.
      Analysis of the rates of tuberculosis morbidity and mortality showed that the
      epidemic situation associated with tuberculosis remained to be of strain in
      Russia in 2005. This is evidenced by high tuberculosis morbidity and mortality
      rates and their increase. In 2005, there was a considerable rise in the frequency
      of recurrent tuberculosis and, as before, the high incidence of extrapulmonary
      tuberculosis, such as tuberculosis of the meninx, central nervous system, and
      bones and joints, in children aged 0-14 years. In 2005, as in previous years, the
      peak of tuberculosis morbidity was seen in young age groups (25-45 years)
      irrespective of gender. In 2005 versus 2004, a 3.8% increase in tuberculosis
      mortality was due to higher death rates among patients with chronic tuberculosis.

PMID- 17500219
TI  - [Role of familial and nonfamilial contacts in the incidence of childhood
      tuberculosis].
AB  - Statistics and data on 101 firstly detected children with active tuberculosis in
      Kemerovo were studied. In 2003 to 2005, there was a marked rise in tuberculosis
      morbidity among children in the Kemerovo Region, to the utmost in Kemerovo.
      During a tuberculosis epidemic, a nonfamilial contact mainly with overlooked
      bacterium-isolating adults plays a leading role in the incidence of tuberculosis.
      A negligible nonfamilial contact with the registered patients is also of no small
      importance. Ineffective vaccination increases morbidity rates, in infancy in
      particular. Timely detection of tuberculosis in adults is the basic way of
      reducing childhood morbidity.

PMID- 17500220
TI  - [The early period of primary "conversion" tuberculous infection in atopic
      diseases].
AB  - The early period of tuberculous infection was comparatively analyzed in 100
      children with atopic diseases. The risk factors of tuberculosis, tuberculin
      sensitivity in mass and individual tuberculin diagnosis, and total IgE levels
      were studied. Less tuberculin sensitivity was revealed. In-effective vaccination
      was more frequently seen. Tuberculosis contamination leads to a reduction in
      serum total IgE levels.

PMID- 17500221
TI  - [Mortality due to recurrent tuberculosis in the Sverdlovsk Region].
AB  - In 2004 to 2005, recurrent tuberculosis in the structure of tuberculosis
      mortality averaged 21.6% in the Sverdlovsk Region. Predominantly males (84.0%)
      aged 45 years or more (62.0%) living in small towns and rural areas (56.9%),
      mainly the unemployed (97.7%), and ex-prisoners (30.3%) die from recurrent
      tuberculosis. The bulk of the patients (64.7%) survived less than 1 year after
      notification of recurrent tuberculosis or a recurrence was revealed only after
      death. Those who died from recurrent tuberculosis had not asked for a medical aid
      before its detection (23.1%) or had asked three months or more after the
      occurrence of significant clinical signs of the disease (34.0%). Refusals to be
      admitted (16.2%) and treated in the outpatient setting (28.7%) and multiple
      hospital discharges due to incompliance (20.7%) should be regarded as the main
      causes of progressive tuberculosis among the contingents of a tuberculosis
      controlling service contingents dying from recurrent tuberculosis.

PMID- 17500222
TI  - [The new combined antituberculous drug: the original combined antituberculous
      drug dioxazid].
AB  - The new combined antituberculous drug dioxazid was designed on the basis on the
      synergism of isoniazid and dioxidine. The dosage form of the drug is a
      lyophilized powder (containing dioxidine, 100 mg, and isoniazid, 250 mg) in
      flasks. Its activity and toxicity were tested in an experiment on laboratory
      animals. Clinical studies were conducted in the treatment of patients with
      tuberculous empyema (n = 25) and those with endobronchial pathology of
      tuberculosis and comorbid genesis (n = 30). Dioxazid was ascertained to show a
      good efficacy. At the same time, the doses of this combined drug, recommended for
      the treatment of tuberculosis, are much smaller than those of both that are
      components of the combination, which are used alone. The side effects
      characteristic for each component are not potentiated when isoniazid and
      dioxidine are concurrently used in the developed dosage form.

PMID- 17500223
TI  - [Natural killer cell immunodeficiency and herpesvirus infection in tuberculosis].
AB  - An inverse correlation was shown between the activity of natural killer cells
      (NKC) and the activated infection to herpes simplex virus (HSV)-1 and HSV-2.
      There was a significant reduction in CD56+ cells in patients who had a history of
      a concomitance of pulmonary tuberculosis and HSV-2 infection. In patients with
      tuberculosis, the decreased activity of NKC may activate HSV-1 infection, with
      its further involvement as an independent factor in the development of
      meningoencephalitis.

PMID- 17500224
TI  - [The proinflammatory activity of bronchoalveolar lavage fluid in patients on an
      exacerbation of pulmonary tuberculosis].
AB  - The proinflammatory activity of bronchoalveolar lavage fluid (BALF) was studied
      in 40 patients with an exacerbation of pulmonary tuberculosis, by applying the
      biological test system--donor blood. The supernatant of BALF was purified by
      milli pore filtration and added to blood, and the nitro blue tetrazolium (NBT)
      recovery test was carried out. Hanks (balanced salt) solution was used in the
      control. The proinflammatory effect of BALF was determined as the ratio of the
      count of diformazan-positive neutrophils in test and control samples (stimulation
      index (SI)). BALF with a low inflammatory activity suppressed the reaction of
      donor blood neutrophil-induced NBT recovery (SI < 1.0). On the contrary, BALF
      from patients with a high inflammation activity intensely stimulated donor
      neutrophil-induced NBT recovery (SI > 1.5). In patients with the high
      proinflammatory activity of BALF, the neutrophils obtained during bronchoalveolar
      lavage restored the parameters of the NBT test twice more actively than in those
      with a low proinflammatory activity of BALF. The findings suggest that the
      assessment of the proinflammatory activity of BALF determines the activity of
      exacerbated tuberculosis that is exudative and destructive with the purpose of
      optimizing immunomodulating therapy.

PMID- 17500225
TI  - [Electroneuromyographic study in patients with spinal tuberculosis].
AB  - Clinical materials were obtained on a comprehensive examination of 64 patients
      with complicated tuberculous spondylitis. To determine the pattern and severity
      of spinal cord impairments, electromyographic (EMG) and electroneuromyographic
      (ENMG) studies were used to study the state of Ja-afferents, alpha-4-gamma
      motoneurons, and afferents of the reflectory ring closing at the level of
      different. Comparison of the clinical picture and EMG data of neuromuscular
      excitatory transmission permits determination of the mechanism responsible for
      the neuroparalytic syndrome. Therefore, EMG and ENMG can yield a complete picture
      of a pathological process, vascular disorders in particular, and the functional
      state of the spinal cord.

PMID- 17500226
TI  - [Tuberculous pleurisy in elderly and senile persons: its clinical picture and
      diagnosis].
AB  - The timeliness of detection and clinical manifestations were analyzed in 132
      patients aged 60 to 92 years who had tuberculous exudative pleurisy (TEP). In
      this age group, TEP was encountered twice more frequently seen than in young
      patients, concurrent with active pulmonary tuberculosis, and, in 33% of cases,
      attended by bacterial isolation. The obliterated picture, a mild response to the
      Mantoux test, X-ray features, and significant comordibity make the diagnosis
      difficult. To enhance the efficiency of a diagnosis of tuberculous pleurisy, it
      is necessary to view each patient with pleural effusion as a potential patient
      with tuberculous pleurisy and refer him/her for a phthisiologist to make an after
      examination.

PMID- 17500227
TI  - [Treatment for progressive pulmonary tuberculosis with a complex of stress
      limiting drugs].
AB  - The study of the performance of major adaptive systems and the parameters of a
      hemogram in 63 patients with progressive pulmonary tuberculosis has established
      the stage of anxiety of a distress reaction, which serves as a pathogenetic
      rationale for the prescription of a complex of stress-limiting drugs, including
      sodium hydroxybutyrate, glycine, dalargin, and tocopherol acetate. The use of
      these agents in combination with intensive antituberculous therapy promotes a
      rapid progression of the stage of anxiety of the adaptation syndrome to the stage
      of resistance and reduces the time of stabilization of the patients' status and
      the number of fatal outcomes.

PMID- 17500229
TI  - [Formation of incentives to recovery and compliance of a chemotherapy regimen in
      patients with tuberculosis].

PMID- 17500228
TI  - [Characteristics of A-interferon-generated dendritic cells in patients with
      pulmonary tuberculosis].
AB  - The phenotype of the dendritic cells (DC) generated from the adhesion fraction of
      mononuclear cells in the presence of GM-CSF and alpha-interferon was studied in
      patients with pulmonary tuberculosis. Despite the absence of significant
      differences in the count of mature CD83+DCs in the groups of patients (n = 38)
      and healthy donors (n = 30), elevated CD14(+)-monocyte levels and few activated
      CD25(+)-DCs were indicative of the impaired process of DC maturation/generation
      in patients with pulmonary tuberculosis, particularly in a subgroup of patients
      with a low T-cell proliferative response against PPD (PPD-anergy, n = 10). The
      patients with tuberculosis showed the lower relative levels of CD11c(-)-CD123(+)
      DC and the normal levels of myeloid CD11c(+)D123(-)DCs. However, in patients with
      PPD-anergy, the content of myeloid CD11c(+)CD123(-)-DCs was significantly higher
      than that in PPD-reactive patients. Moreover, the patients with PPD-anergy were
      characterized by the elevated peripheral blood levels of CD14+CD16(+)-monocytes,
      which was associated with the high suppressive activity of monocytes (r(s) =
      0.53; p < 0.05). The impaired process of DC generation/maturation in patients
      with pulmonary tuberculosis is believed to be associated with the changes in the
      phenotypic and functional properties of monocytes and to be a cause of an
      inadequate antigen-specific response in tuberculous infection.

PMID- 17500230
TI  - [Interaction of hepatitis C virus with cytoplasmic membrane receptors].
AB  - The review presents the structure and incidence of these cell receptors and their
      role in the entry of hepatitis C virus. Some cell receptors, such as CD81,
      lipoprotein receptors, asialoglycoprotein receptors, DC-SIGN and L-SIGN, human
      scavenger receptors class B type I, cell surface heparin sulfate have been
      recently recognized as hepatitis C virus receptors.

PMID- 17500231
TI  - [siRNA-mediated inhibition of respiratory syncytial virus replication].
AB  - The effect of siRNA against respiratory syncytial virus (RSV) was investigated in
      the cultured cells. MA104 cells were inoculated by RSV and transfected by
      different variants of siRNA against RSV phosphoprotein (P) mRNA or non-specific
      siRNA as a control. The inhibition of RSV was assessed by microscopically
      studying the cells, titrating the virus, and estimating viral RNA quantity in the
      culture supernatants by real-time polymerase chain reaction (PCR). The most
      potent variants of siRNA caused an up to 8-day delay of microscopically
      detectable syncytium generation to 8 days, an up to 280-fold decrease in viral
      titers, and an up to 40-fold reduction in viral RNA quantity in the supernatants,
      as compared to the controls (p < 0.001). RSV mRNA is a suitable target for siRNA
      mediated RSV replication inhibition, promising an advance in the treatment of RSV
      infection.

PMID- 17500232
TI  - [Growth characteristics of single gene mutants of A/Leningrad/134/57(H2N2)
      influenza virus and cold-adapted mutant A/Leningrad/134/17/57(H2N2)].
AB  - The authors examined a role of some mutated A/Leningrad/134/17/57(H2N2) virus
      genes in the realization of growth characteristics. The latter of single gene
      reassortants (SGRs) (PB2, PB1, PA, M, and NS), epidemic virus and attenuation
      donor were assessed by infecting MDCK cells and hen embryos at a low inoculation
      index. Viral replication in the hen embryos and cultured tissue was compared at
      34 degrees C. The viruses and reassortants tested showed a high growth capacity
      in the hen embryos (9.5-10.5 Ig TCID50). The growth curves of viruses were
      studied on the cultured MDCK cells at a low inoculation index indicated that
      Len/17 and the single gene reassortants M and NS had the highest growth capacity.
      At the same time the growth of both PB1 and PB2 SGRs was less extensive. The
      reproduction of PB2 SGR was 100-1000 times less than that of other viruses
      tested. M, NS, and PA gene mutations did not affect viral growth in hen embryos
      and cultured tissue while PB2 gene mutation and its constellations with other
      genes caused a reduction in viral growth in the cultured tissue.

PMID- 17500233
TI  - [Analysis of genomes of two rubella virus strains from the 2004-2005 outbreaks in
      West Siberia].
AB  - Two outbreaks of rubella infections notified in the Tomsk and Kemerovo Regions
      were investigated. Two rubella virus strains from one patient in each outbreak
      were isolated and genetically characterized. Reverse transcription polymerase
      chain reaction was used to reveal partial E1 gene sequence at a length of 915
      nucleotides. Analysis indicated that the rubella virus strains circulating in the
      West-Siberian region belonged to international genetic 1g group, which had been
      first detected in Russia.

PMID- 17500234
TI  - [Study of the phylogenetic relations of Puumala hantaviruses, by using the mutual
      information calculating method].
AB  - Phylogenetic relations were investigated in the group of Puumala viruses (the
      genus Hantavirus, the family Bunyaviridae) by the mutual information showing the
      similarity of the nucleotide sequences of S- and M-genome segments. There was
      evidence that recombination events might occurr in some Eurasian Puumala viruses
      (Scandinavian and West-Siberian genotypes). The investigation revealed the
      conservative sites available in the S and M segments that were common to most
      Puumala viruses, as well as the preservation of alternation and mutual
      arrangement of these sites in the S and M segments even for greatly diverging
      genotypes, which may be used in the detection of recombination events in Puumala
      viruses during further studies.

PMID- 17500235
TI  - [Rimantadine and arbidol sensitivity of influenza viruses that caused epidemic
      morbidity rise in Russia in the 2004-2005 season].
AB  - The study of the activity of arbidol against epidemic influenza A and B virus
      strains (2002-2005) in the cultured MDCK cells showed the higher sensitivity of
      enzyme immunoassay than that of hemagglutination test. The influenza A virus
      strains tested, including those resistant to rimantadine (5 microg/ml), were
      sensitive to arbidol (10 microg/ml). The population of influenza B virus strains
      was heterogeneous in this indicator, 43% of the strains being less sensitive to
      arbidol. There was an increase in the number of rimantadine-resistant influenza
      A(H3N2) virus strains (10-18%) in our country during 3 epidemic seasons. The
      sequencing analysis of protein M2-endoding gene revealed the amino acid
      replacement of serine by asparagine in position 31, which is characteristic of
      rimantadine-resistant strains. Arbidol in combination with rimantadine
      potentiated the effect of viral reproduction in the cultured cells, as compared
      with the effect produced by the same concentrations of the drugs used alone.

PMID- 17500236
TI  - [Screening of biopolymers from sea hydrocoles affecting the adsorption of Hantaan
      virus].
AB  - The biopolymers extracted from sea hydrocoles were screened and a group of
      sulfated polysaccharides--fucoidans having a pronounced inhibitory effect on the
      adsorption of Hantaan virus in the cultured Vero E6 cells was identified. The
      mechanism of action of sulfated polysaccharides was realized through competitive
      carbohydrate-specific binding to cell membrane receptors and through ligand
      receptor interaction and blocking of Hantaan virus glycoproteins (G1 and G2).

PMID- 17500237
TI  - [Comparative study of hemostasis and cytokine production in experimental Dengue
      virus infection].
AB  - Some parameters of hemostasis and cytokine production during the fatal and
      nonfatal course of experimental human versus murine infection caused by Dengue
      virus (DV) were studied. Its lethal dose administration induced a rapid
      development of anemia, thrombocytopenia and a change in packed cell volume. These
      changes were not so profound in the nonfatal group of infected mice. There was an
      excess production of both proinflammatory (TNF-alpha, IL-1beta) and anti
      inflammatory (IL-6, IL-10) cytokines in the fatal group. In mice of this group,
      the early rise of IFN-gamma and IL-12 corresponded to the parameters observed in
      patients with severe forms of DV infection. The findings provide evidence that
      the proposed model may be used for the experimental study of the
      immunopathogenesis of the disease.

PMID- 17500238
TI  - [4647-cell culture for preparation of recombinant bivaccine against smallpox and
      hepatitis B].
AB  - The seeding and working banks of a 4647-cell culture have been created. The 4647
      cell culture in these banks has a high proliferative activity, as well as the
      morphology, typical of this line, and the karyotype and the enzymogram, which are
      characteristic for the cells of an African talapoin (Cercopithecus aethiops). The
      culture is not contaminated with bacteria, fungi, Mycoplasma, and viruses,
      including oncoviruses. The deposited 4647 cells have high viral productive
      properties for the accumulation of the recombinant virus strain b7,5S2-S vaccine
      and keep the stability of all biological properties during a long-term
      cultivation. The continuous 4647 cell line was tested at the L. A. Tarasevich
      State Institute of SK. The seeding and working banks of 4647-cell culture at
      passages 108 and 128 are recommended as a substrate for cultivation of the strain
      b7,5S2-S vaccinia, used to prepare a bivaccine against smallpox and hepatitis B.

PMID- 17500239
TI  - [Biological microchip for identification of orthopoxviruses and agents causing
      the same clinical picture as in smallpox].
AB  - A method based on hybridization of simultaneously amplified gene fragments of
      orthopoxviruses and herpesviruses with oligonucleotide probes immobilized on a
      microarray has been developed. The method permits identification of 6
      orthopoxvirus species and three types of herpesviruses, including Varicella
      zoster, within 6 hours.

PMID- 17500240
TI  - [Enzyme-linked immunosorbent assay for detection of antibodies to porcine
      reproductive and respiratory syndrome virus, by using recombinant nucleocapsid
      protein N].
AB  - Recombinant nucleocapsid (rN) protein N of porcine reproductive and respiratory
      syndrome virus (PRRSV) was prepared, by using the E. coli expressiom system.
      Insertion of a polyhistidine marker into the structure of the protein allowed the
      latter to be purified by metal-chelate affinity chromatography. The purity of
      protein was confirmed by PAAG electrophoresis and its immunospecificity was
      verified by immunoblotting using rN-specific monoclonal antibodies. The protein
      was used as an antigen to develop indirect ELISA of PRRSV antibodies. ELISA was
      shown to be highly sensitive and specific.

PMID- 17500241
TI  - Erickson Health takes long view with technology. The Nursing Information
      Technology Innovation Award.

PMID- 17500242
TI  - Making sense of business analytics. Organizations seek to gain efficiencies using
      I.T. to measure clinical and financial performance.

PMID- 17500243
TI  - First responders not first for I.T. But changes are coming as voice, data
      converge and discussions get serious about funding.

PMID- 17500244
TI  - Wireless system a very good listener.

PMID- 17500245
TI  - I.T. helps provider avoid ID crisis.

PMID- 17500246
TI  - Readers' perspectives. The recent revisions to federal rules to permit
      information technology donations to physicians will help spur I.T. adoption. Do
      you agree or disagree?

PMID- 17500247
TI  - Ethical guidelines and guidelines on ethics are not the same.

PMID- 17500248
TI  - Blessed are the pure in heart.

PMID- 17500249
TI  - Spotlight on claudication: an important disease gets attention.

PMID- 17500250
TI  - Update on idiopathic pulmonary fibrosis: the role of gamma interferon and
      cytokines.

PMID- 17500251
TI  - On headache tablets: headache incantations from Ur III (2113-2038 BC).

PMID- 17500252
TI  - Disruptive physician behaviors.

PMID- 17500253
TI  - Giant cell myocarditis presenting as isolated right ventricular dysfunction.

PMID- 17500254
TI  - Managing the medication portfolio and avoiding polypharmacy in the older adult.

PMID- 17500255
TI  - Hospital community benefits, 2005.

PMID- 17500256
TI  - Taking a social marketing approach to implementing clinical best practices: a
      pilot project.

PMID- 17500257
TI  - National provider identifiers--implications for the local provider community.

PMID- 17500258
TI  - Off-label drug use.

PMID- 17500259
TI  - Shape strategy with docs' location in mind.

PMID- 17500260
TI  - Worried about retail clinics, some providers are fighting back.

PMID- 17500261
TI  - Image makeover.

PMID- 17500262
TI  - Choose the right reporting structure for physician reps.

PMID- 17500263
TI  - The hazards of alarm overload. Keeping excessive physiologic monitoring alarms
      from impeding care.
AB  - There are many reasons that the numbers of physiologic monitoring system alarms
      that clinicians must respond to can grow out of control. This article identifies
      the most common reasons and delivers recommendations for handling them. Although
      alarms are an important part of patient care and safety, they can easily reach
      quantities that overwhelm nurses, thereby compromising alarm effectiveness.
      Excessive quantities of alarms may desensitize nurses, leading them to not
      promptly respond to alarms or to inappropriately inactivate them. And alarms that
      ultimately prove to have been unnecessary can needlessly distract nurses or pull
      them away from other tasks. ECRI doesn't believe that there is a single "cure
      all" for controlling alarm quantities. Rather, the way to combat alarm overload
      is to first identify the various sources of excessive alarms and to then take
      actions to individually address each source. This article recommends key actions
      to take and describes how these actions can be organized into a systematic plan.
      The effect of these efforts should be better clinical efficiency and improved
      patient safety.

PMID- 17500264
TI  - Portable/transport ventilators: our latest look at what's on the market.
AB  - This article presents ECRI's purchasing guidance for 11 currently marketed
      portable/transport ventilators from six suppliers. We highlight-and update-some
      of our key findings for three models that we had previously evaluated, and we
      compare these products with eight additional models that are now available, but
      that have not been subjected to ECRI's full evaluation protocol. Specifically, we
      compare ventilator features and specifications and describe which models are the
      most appropriate to consider for (1) home-care/long-term-care settings and (2) in
      hospital transport.

PMID- 17500265
TI  - Hazard report. Switch failure may lead to patient injury from Siemens 3D-TOP x
      ray tube.

PMID- 17500266
TI  - Pulse oximetry: choosing the right sensor and applying it correctly.

PMID- 17500267
TI  - Instrumental organization/Cancer center preps for surgery.

PMID- 17500268
TI  - Room with a view. Limited site makes for remarkable vistas.

PMID- 17500269
TI  - Dignity and style. Bariatric furniture designs hit their stride.

PMID- 17500270
TI  - Calling ahead. Upgrading telecom equipment for the future.

PMID- 17500271
TI  - The OR challenge. New technologies lead to increased complexity.

PMID- 17500272
TI  - Zooming in. A closer look at the 'AIA Guidelines' as they relate to hospitals.

PMID- 17500273
TI  - Sound science. Taking hospital cleaning to the next level.

PMID- 17500274
TI  - [Plea for development of nursing knowledge. Interview by Sylvie Warnet].

PMID- 17500277
TI  - [Diseases of the thyroid].

PMID- 17500278
TI  - [Addison's disease].

PMID- 17500279
TI  - [Cushing syndrome].

PMID- 17500280
TI  - [Pheochromocytoma].

PMID- 17500281
TI  - [Conn syndrome].

PMID- 17500282
TI  - [Hirsutism].

PMID- 17500283
TI  - [Nursing practice in endocrinology].

PMID- 17500284
TI  - [The nasogastric tube].

PMID- 17500285
TI  - [Helping bereaved families].

PMID- 17500286
TI  - [Emergency care at Fresnes prison].

PMID- 17500287
TI  - [Toronto nurses fighting against severe acute respiratory syndrome].

PMID- 17500289
TI  - [Learning, doing, collaborating, transmitting: health professionals' words in
      Brittany].

PMID- 17500290
TI  - [Carbimazole, synthetic antithyroid drug].

PMID- 17500291
TI  - [Creatinine].

PMID- 17500292
TI  - [Art at the patient's bedside thanks to Tournesol hospital artists].

PMID- 17500294
TI  - Making it happen: the LPN to RN transition.

PMID- 17500295
TI  - Helen Gorecki. Interview by Sarah Qualls.

PMID- 17500296
TI  - Nurse practitioners in the driver's seat: redefining the health care experience.

PMID- 17500297
TI  - Sim Man: not your grandma's nursing education.

PMID- 17500298
TI  - Nurses at the forefront of a pandemic: HIV/AIDS nurses.

PMID- 17500299
TI  - The child & adolescent mental health crisis: closing the service gap.

PMID- 17500300
TI  - Eating disorder paradigms for the new millennium: do "attachment" and "culture"
      appear on brain and genome scans?

PMID- 17500301
TI  - Getting beneath the phenotype of anorexia nervosa: the search for viable
      endophenotypes and genotypes.
AB  - Treatment for anorexia nervosa has changed little from that described by Gull
      over a century ago. To focus merely on symptomatic relief from "not eating," as
      occurs with some forms of hospital care, is primitive. The evidence base to guide
      treatment is thin. Nevertheless, there is hope that better understanding of the
      causes and maintaining factors may translate into more sophisticated treatments.
      This review aims to look beyond the overt and startling "not eating" phenotype of
      anorexia nervosa and consider eating disorder endophenotypes. The first part of
      the review sets the eating behaviour, clinical, and psychopathological features
      into the context of what is now understood about the central control of appetite.
      The evidence base for a framework of potential eating disorder endophenotypes
      follows. Finally, ideas about how to translate endophenotypes into treatment are
      introduced.

PMID- 17500302
TI  - Phenotypes, endophenotypes, and genotypes in bulimia spectrum eating disorders.
AB  - OBJECTIVES: To review the main phenomenological variants observed among bulimia
      spectrum syndromes and the factors believed to act etiologically for them and
      also to generate an etiologic model that accommodates known heterogeneities
      within the population suffering bulimic syndromes. METHOD: Defining bulimic
      syndromes broadly, we address threshold and subthreshold forms of bulimia nervosa
      (BN) and also the provisional or newly proposed diagnoses of binge eating
      disorder (BED) and purging disorder (PD). We review evidence bearing on the
      validity of these diagnostic entities and on the place of sociocultural, family
      developmental, neurobiological, and genetic factors in a multidimensional
      etiologic model for these classifications. RESULTS: Available data validate
      certain bulimic phenotypes and subphenotypes that are characterized by such
      traits as impulsivity or affective instability. Findings associate subphenotypic,
      or trait-based, variations with putative endophenotypes, such as reduced
      serotonin transporter activity, and with candidate genotypes affecting the
      serotonin system; the data also indicate intriguing correspondences between gene
      environment interactions and subphenotypic variations along such dimensions as
      novelty seeking. CONCLUSIONS: Bulimic syndromes sometimes reflect a primary
      disruption of controls over mood, impulses, and appetite in individuals showing
      marked psychopathology; at other times, they reflect a more circumscribed erosion
      of appetitive controls in relatively intact individuals, following prolonged
      dieting. We argue that dimensional perspectives involving careful attention to
      comorbid personality traits and symptoms are needed to accommodate existing
      heterogeneities within the population suffering from bulimia and to characterize
      the etiologic roles of familial-developmental, neurobiological, and genetic
      variables (and of interactions among these variables) in bulimic syndromes.

PMID- 17500303
TI  - Mental health service use among adolescents and young adults with major
      depressive disorder and suicidality.
AB  - OBJECTIVES: Despite being recognized as a serious public health concern,
      suicidality among adolescents and young adults is frequently missed, and
      completed suicide remains the second leading cause of death for young Canadians.
      With such close links between depression, suicidality, and completed suicide, any
      intervention must address all 3 of these issues. However, to develop effective
      interventions, we must understand the types and rates of mental health service
      use among adolescents and young adults. This study examines service use rates in
      young Canadians with depression and suicidality and the influence of sex on the
      types of service provider chosen. METHODS: We used data from the Canadian
      Community Health Survey: Mental Health and Well-Being. Our sample included 619
      individuals, aged 15 to 24 years, who screened positive for depression and
      suicidality in the past 12 months. We examined mental health service use rates in
      general and by provider type. RESULTS: Among adolescents aged 15 to 18 years with
      depression, 40% had not used any mental health services. This rate was higher for
      adolescents with suicidality at 50%. In young adults aged 19 to 24 with
      depression, 42% had not used any mental health services. Among young adults with
      suicidality, 48% had not accessed services. Female adolescents and young adults
      were more likely to receive services from nonspecialty mental health providers.
      CONCLUSIONS: In Canada, many adolescents and young adults with depression and
      suicidality do not receive mental health services. Further, there may be a
      preferential treatment of young men by mental health specialists. Further
      research is needed to understand the quality of care received by these young
      Canadians and the factors influencing service use.

PMID- 17500304
TI  - Stress and psychological distress among SARS survivors 1 year after the outbreak.
AB  - OBJECTIVE: Our study examined the stress level and psychological distress of
      severe acute respiratory syndrome (SARS) survivors 1 year after the outbreak.
      METHOD: During the SARS outbreak in 2003, we used the 10-item Perceived Stress
      Scale (PSS-10) to assess SARS survivors treated in 2 major hospitals (non-health
      care workers, n = 49; health care workers, n = 30). We invited SARS survivors
      from the same hospitals (non-health care workers, n = 63; health care workers, n
      = 33) to complete the PSS-10 again in 2004. At that time, they were also asked to
      complete the General Health Questionnaire (GHQ-12) and measures of depression,
      anxiety, and posttraumatic symptoms. PSS-10 scores were also obtained from
      matched community control subjects during the outbreak (n = 145) and again in
      2004 (n = 112). RESULTS: SARS survivors had higher stress levels during the
      outbreak, compared with control subjects (PSS-10 scores = 19.8 and 17.9,
      respectively; P < 0.01), and this persisted 1 year later (PSS-10 scores = 19.9
      and 17.3, respectively; P < 0.01) without signs of decrease. In 2004, SARS
      survivors also showed worrying levels of depression, anxiety, and posttraumatic
      symptoms. An alarming proportion (64%) scored above the GHQ-12 cut-off that
      suggests psychiatric morbidity. During the outbreak, health care worker SARS
      survivors had stress levels similar to those of non-health care workers, but
      health care workers showed significantly higher stress levels in 2004 (PSS-10
      score = 22.8, compared with PSS-10 score = 18.4; P < 0.05) and had higher
      depression, anxiety, posttraumatic symptoms, and GHQ-12 scores. CONCLUSIONS: One
      year after the outbreak, SARS survivors still had elevated stress levels and
      worrying levels of psychological distress. The situation of health care worker
      SARS survivors is particularly worrying. The long-term psychological implications
      of infectious diseases should not be ignored. Mental health services could play
      an important role in rehabilitation.

PMID- 17500305
TI  - Immediate and sustained psychological impact of an emerging infectious disease
      outbreak on health care workers.
AB  - OBJECTIVE: To assess the immediate and sustained psychological health of health
      care workers who were at high risk of exposure during the severe acute
      respiratory syndrome (SARS) outbreak. METHODS: At the peak of the 2003 SARS
      outbreak, we assessed health care workers in 2 acute care Hong Kong general
      hospitals with the Perceived Stress Scale (PSS-10). One year later, we reassessed
      these health care workers with the PSS-10, the 21-Item Depression and Anxiety
      Scale (DASS-21), and the Impact of Events Scale-Revised (IES-R). We recruited
      high-risk health care workers who practised respiratory medicine and compared
      them with nonrespiratory medicine workers, who formed the low-risk health care
      worker control group. RESULTS: In 2003, high-risk health care workers had
      elevated stress levels (PSS-10 score = 17.0) that were not significantly
      different from levels in low-risk health care worker control subjects (PSS-10
      score = 15.9). More high-risk health care workers reported fatigue, poor sleep,
      worry about health, and fear of social contact, despite their confidence in
      infection-control measures. By 2004, however, stress levels in the high-risk
      group were not only higher (PSS-10 score = 18.6) but also significantly higher
      than scores among low-risk health care worker control subjects (PSS-10 score =
      14.8, P < 0.05). In 2004, the perceived stress levels in the high-risk group were
      associated with higher depression, anxiety, and posttraumatic stress scores (P <
      0.001). Posttraumatic stress scores were a partial mediator of the relation
      between the high risk of exposure to SARS and higher perceived stress.
      CONCLUSIONS: Health care workers who were at high risk of contracting SARS appear
      not only to have chronic stress but also higher levels of depression and anxiety.
      Front-line staff could benefit from stress management as part of preparation for
      future outbreaks.

PMID- 17500306
TI  - Efficacy and safety of antidepressants for treatment of depression in Alzheimer's
      disease: a metaanalysis.
AB  - OBJECTIVE: Depression in patients with Alzheimer's disease (AD) is common (15% to
      63%) and is associated with significant morbidity and increased mortality. Our
      objective was to quantitatively summarize the data on the efficacy and safety of
      antidepressant treatment for depression complicating AD. METHOD: We performed a
      metaanalysis of randomized, double-blind, placebo-controlled trials of
      antidepressants with a database search of the English literature (up to 2006) and
      a manual search of references in the retrieved articles. We extracted the
      proportion of subjects who responded and remitted, experienced adverse events
      (AEs), discontinued treatment due to AEs, or discontinued treatment for any
      reason. Cognition scores were also extracted. RESULTS: We included 5 studies,
      which involved 82 subjects treated with antidepressants and 83 subjects who
      received placebo treatment. Antidepressants were superior to placebo for both
      treatment response (odds ratio [OR] 2.32; 95% confidence interval [CI], 1.04 to
      5.16) and remission of depression (OR 2.75; 95% CI, 1.13 to 6.65). There were no
      significant differences between the 2 groups for change in cognition (weighted
      mean difference -0.71, 95% CI, -3.20 to 1.79), overall dropouts (OR 0.70; 95% CI,
      0.29 to 1.66) or dropout due to AEs (OR 1.41; 95% CI 0.36 to 5.54). The numbers
      needed to treat for one additional AD patient to respond to antidepressant
      treatment were 5 (95% CI, 3 to 59) and 5 (95% CI, 2 to 24) for remission of
      depression. CONCLUSIONS: Antidepressant treatment for depression in AD is
      efficacious, with rates of discontinuation that are comparable to placebo.
      Nonetheless, clinicians must be vigilant regarding the potential side effects of
      antidepressants in this population.

PMID- 17500307
TI  - The sensitivity of the K6 as a screen for any disorder in community mental health
      surveys: a cautionary note.
AB  - OBJECTIVE: Short screening instruments, which exclude respondents unlikely to
      have psychiatric disorders, can make epidemiologic surveys shorter and more cost
      effective. The Kessler 6-Item Psychological Distress Scale (K6), a measure of
      generalized distress, has been proposed for this role and has shown good
      agreement with the Composite International Diagnostic Interview (CIDI). However,
      performance of the K6 may vary for individual disorders or combinations of
      disorders. In this report, we examine the ability of the K6 to detect disorders
      among respondents in different diagnostic categories. METHOD: We used data from
      Cycle 1.2 of the Canadian Community Health Survey to assemble 5 groups of
      respondents with different 12-month psychiatric disorders (n = 4481). A sixth
      group comprised those with 2 or more disorders. We examined the sensitivity of
      the K6 among respondents with an individual disorder as well as those with
      multiple disorders. RESULTS: The sensitivity of the K6 varies significantly by
      disorder; it is highest among respondents with multiple disorders and lowest
      among those with agoraphobia only. CONCLUSIONS: Use of the K6 as a screen for the
      CIDI is likely to result in biased prevalence estimates. However, both
      instruments should be compared with a third standard to fully assess the benefits
      and drawbacks of their combination.

PMID- 17500308
TI  - Does mindfulness meditation improve anxiety and mood symptoms? A review of the
      controlled research.
AB  - OBJECTIVE: To review the impact of mindfulness-based stress reduction (MBSR) on
      symptoms of anxiety and depression in a range of clinical populations. METHOD:
      Our review included any study that was published in a peer-reviewed journal, used
      a control group, and reported outcomes related to changes in depression and
      anxiety. We extracted the following key variables from each of the 15 studies
      identified: anxiety or depression outcomes after the MBSR program, measurement of
      compliance with MBSR instructions, type of control group included, type of
      clinical population studied, and length of follow-up. We also summarized
      modifications to the MBSR program. RESULTS: Measures of depression and anxiety
      were included as outcome variables for a broad range of medical and emotional
      disorders. Evidence for a beneficial effect of MBSR on depression and anxiety was
      equivocal. When active control groups were used, MBSR did not show an effect on
      depression and anxiety. Adherence to the MBSR program was infrequently assessed.
      Where it was assessed, the relation between practising mindfulness and changes in
      depression and anxiety was equivocal. CONCLUSIONS: MBSR does not have a reliable
      effect on depression and anxiety.

PMID- 17500309
TI  - Efficacy and safety of oxcarbazepine in bipolar disorder.

PMID- 17500310
TI  - Re: Community treatment orders for psychiatric patients: the emperor with no
      clothes.

PMID- 17500311
TI  - Comparison of thermophilic and mesophilic one-stage, batch, high-solids anaerobic
      digestion.
AB  - The concept of starting up a batch, high-solids anaerobic digester by simply
      flooding the bed with a pH-buffer solution was tested using a mixture of
      vegetable waste and wood chips as feedstock at mesophilic (38 degrees C) and
      thermophilic (55 degrees C) conditions. At both temperatures stable and balanced
      methanogenesis was rapidly established within four days and was sustained until
      substrate was exhausted. Methanogenesis was more rapidly initiated in the
      thermophilic digester than in the mesophilic digester. Acetic, propionic and
      butyric acids accumulated in the leachate of both digesters during the start-up
      of digestion of uninoculated batch of waste. Thereafter all acids were degraded;
      which was quicker in the thermophilic digester. The accumulation and degradation
      of these acids was slower in the mesophilic digester. These studies showed that
      inoculum for carrying out thermophilic and mesophilic anaerobic digestion is
      readily available within the waste and its activity for complete mineralization
      of organic matter can be enhanced and sustained by providing adequate alkalinity.
      By employing a process in which anaerobic digestion of subsequent batches of
      waste was carried out by flooding with leachate drained from the digestion of a
      previous batch of waste, the volatile organic acid accumulation was maintained
      low and 95% of the methane yield potential of the waste was produced in 11 days
      under thermophilic conditions as opposed to 27 days under mesophilic conditions.

PMID- 17500312
TI  - Selective control of cyanobacteria in eutrophic pond by a combined device of
      ultrasonication and water pumps.
AB  - A combined device consisting of an ultrasonic apparatus and water pumps was
      operated in a eutrophic pond to study its effect on the control of cyanobacteria
      as compared with those of a non-treated, neighboring pond. The combined apparatus
      seemed to be enough to spread the sonicated water to the whole surface of a 9,000
      m3 pond. Although the high rainfall in 2003 resulted in an overall dominance of
      diatoms, cyanobacterial growth was significantly inhibited by the apparatus in
      the treated pond. In addition, the chlorophyll-a concentration and total algae in
      the treated pond were 61 and 53%, respectively, of the levels in the control
      pond. The reduced algal growth (7% of the control) by the combined apparatus was
      mainly due to the inhibition on the growth of cyanobacteria. The cyanobacterial
      proportion in the treated pond, however, increased significantly for several
      days, when the apparatus was stopped. Meanwhile, the proportion of green algae
      increased in the treated pond. The successful selective control of cyanobacteria
      using the combined apparatus suggests that ultrasonication can be a practical
      method to control bloom and toxin production in eutrophic waters.

PMID- 17500313
TI  - Sand capping for controlling phosphorus release from lake sediments.
AB  - In this research, the use of the sand capping technique for controlling
      phosphorus release from lake sediment was evaluated experimentally. Multiple
      acrylic columns were prepared to measure the dissolved oxygen, oxidation
      reduction potential, total phosphorus, and phosphate concentrations of the
      overlying water on the capping layer with thicknesses of 0, 40, and 80 mm. Sand
      capping effectively slowed down the reactions that depleted the dissolved oxygen,
      which as a result, controlled the total phosphorus release from the sediment.
      Oxidation reduction potential of overlying water was estimated by measuring
      dissolved oxygen in situ or vice versa by an empirical model proposed in this
      research. Sediment disturbance should be considered during field construction of
      the cap system. The experimental results showed that phosphorus existed in a more
      stable form with capping than without capping.

PMID- 17500314
TI  - Mathematical model for sizing combined nitrification and pre-denitrification
      activated sludge systems.
AB  - Two mathematical steady-state models for sizing single activated sludge systems
      aimed at nitrogen and organics removal from wastewater are proposed. The
      attention is focused on the combined nitrification system and the pre
      denitrification system, considering three (soluble and particulate biodegradable
      organic matter and ammonia nitrogen) and four (the above cited and nitrate
      nitrogen) substrates, respectively. Growth and decay of two groups of bacteria
      (heterotrophic and autotrophic) are taken into account. If the influent flow
      composition and the kinetic parameters are known and the effluent nitrogen
      concentration is fixed, both models give explicit expressions of the volumes of
      the biological reactors. Moreover, the pre-denitrification model makes it
      possible to define a priori the applicability of the system for a particular
      wastewater. Model applications show that the nitrification reactor volume
      increases in the case of a higher influent organic load or to achieve a higher
      nitrogen ammonia removal efficiency. A smaller denitrification volume is required
      to face a higher influent organic load. A sensitivity analysis on the kinetic
      parameters shows an important influence of the maximum ammonia nitrogen removal
      rate and the ratio between the decay rates of heterotrophic and autotrophic
      biomass on the nitrification reactor volume.

PMID- 17500315
TI  - [Toward a better knowledge of the pesticides used by municipality in rural
      society: example of Limousin Region (France)].
AB  - A survey concerning pesticide uses by municipalities located in countryside
      areas, was carried out through inquiries submitted to 39 different municipalities
      representative of the Limousin area (France) except for Limoges city. The rate of
      answers was 72 % (28 municipalities). Extensive breeding of bovines and sheep
      represents the majority of agricultural practices in this area. The objective of
      this investigation to highlight the operational pesticides uses among different
      municipalities. The main results showed the use of a large number of different
      commercial products (61, representing 46 active molecules) as well as the
      intensive use of herbicides such as Glyphosate. Compared to the usual regional
      agricultural uses in Limousin, the part of Dichlobenil, Diuron, Isoxaben and
      Diflufenicanil used by the municipalities could be strong. The municipalities
      usually try to comply with the safety requirements regarding pesticide uses but
      the need for preventive actions such as the training of municipality workers as
      well as informations regarding alternative weeding techniques is required.
      Moreover, due to the relatively low permeability of the treated surfaces, the
      discharge of pesticides by water run-off can be significant and thus can
      contribute significantly to the pollution of the natural aquatic environments or
      the water resources for water supply.

PMID- 17500316
TI  - Removal of hydrophobic micro-organic pollutants from municipal wastewater
      treatment plant effluents by sorption onto synthetic polymeric adsorbents: batch
      sorption experiments.
AB  - The use of a synthetic form polymer, polypropylene, as a sorbent for hydrophobic
      organic compounds present in municipal wastewater treatment plant effluent was
      investigated. To enhance the sorption capacity of polypropylene for hydrophobic
      organic compounds, polypropylene was coated with a thin layer of n-hexane.
      Sorption of target compounds onto polypropylene and polypropylene coated with n
      hexane was evaluated by carrying out equilibrium and kinetic batch experiments.
      Three polycyclic aromatic hydrocarbons, namely, phenanthrene, fluorene and
      naphthalene, were selected as representative hydrophobic organic compounds for
      experimental purposes. The effect of pH, ionic strength and dissolved organic
      matter on sorption was investigated. The results showed that polypropylene coated
      with n-hexane performed better than polypropylene as a sorbent for polycyclic
      aromatic hydrocarbons, in terms of sorption capacity and sorption kinetics. Ionic
      strength and pH did not have a significant effect on the sorption of polycyclic
      aromatic hydrocarbons. Dissolved organic matter in the form of humic acid did not
      sorb onto polypropylene or polypropylene coated with n-hexane, and the presence
      of dissolved organic matter in the aqueous phase did not significantly affect
      sorption of polycyclic aromatic hydrocarbons.

PMID- 17500317
TI  - Control of lead polluted leachate in a box-scale phytoremediation test using
      common buckwheat (Fagopyrum esculentum Moench) grown on lead contaminated soil.
AB  - The remediation of heavy metal contaminated soil using plants is a technology
      worth developing. However, the overall effect of phytoremediation in high-density
      Pb polluted sites remains unknown. Especially, little information is available
      about the effects of using plants to control lead polluted leachate. Thus, we
      investigated the control of leachate in a box-scale phytoremediation test using
      common buckwheat, a Pb hyperaccumulator, grown on Pb contaminated soil. In the
      presence of buckwheat, the change in volumetric water content was smaller than
      that of the control with rainfall. The total amount of Pb in the leachate
      strongly correlated with the amount of leachate and the decrease in the density
      of Pb in the leachate. During the cultivation period, the total amount of Pb
      leached in the control was 1.28mg per container, while in the presence of
      buckwheat the total amount of Pb was approximately 22.7% of the control.
      Moreover, with buckwheat cultivation, Pb polluted leachate resulting from
      rainwater was prevented. The results suggested that buckwheat was a Pb
      hyperaccumulator and also had a high ability for phytostabilization. Control of
      Pb polluted leachate using buckwheat was shown to be a phytoremediation
      technology applicable to heavily Pb contaminated sites.

PMID- 17500318
TI  - Effect of HRT and slurry concentration on biogas production in cattle dung based
      anaerobic bioreactors.
AB  - The effect of three different cattle dung slurry concentrations (1:1, 1:4 and
      1:9) at three different HRTs of 20, 30 and 40 days was studied at pilot scale for
      one year. The results showed that both biogas yield and methane content of gas
      obtained in 1:4 and 1:9 slurry concentrations were significantly higher than
      those at 1:1 concentration for a given HRT. This was observed for all the three
      HRTs studied. At 1:1 and 1:4 slurry concentrations, methane yield was found to
      increase with HRT. However, at higher dilution of 1:9, increase in HRT from 30 to
      40 days resulted in decrease in methane yield.

PMID- 17500319
TI  - Removal of heavy metals via adsorption on activated carbon synthesized from solid
      wastes.
AB  - The huge quantity of date pits as solid waste byproduct in Saudi Arabia pose a
      problem as they are difficult to biodegrade. The potential of using date pits as
      a cheap precursor to prepare activated carbons was investigated. Steam as well as
      zinc chloride activated carbons were prepared from dates pit. The textural
      properties, including surface area, mean pore radius and total pore volume, were
      determined from the adsorption of nitrogen at 77 K. FT-IR spectroscopy and base
      neutralization capacity were used to determine the surface groups. The adsorption
      of Cu2+, Pb2+ and Cd2+ was studied in equilibrium method. FT-IR investigation of
      un-activated carbons identified phenolic, lactonic, -O-H, quinonic and
      carboxylate groups. For steam and zinc chloride activated carbons, some of the
      adsorption bands either disappeared or become less predominant, depending on the
      acidic or basic nature of the surface. The measurements of BNC indicated that
      steam activated carbons were predominately basic, while zinc chloride activated
      carbons exhibited acidic nature. Physical and chemical activation increase the
      porosity and thereby develop a higher surface area. The adsorption of Cu2+, Pb2+
      and Cd2+ followed the order Pb2+ > Cu2+ > Cd2+. Zinc chloride activated carbons
      had a higher adsorption power compared with steam activated carbons. The
      adsorption behavior was affected by the textural and chemistry of the surface.

PMID- 17500320
TI  - Equilibrium and kinetics of metal biosorption by sludge from a biological
      nutrient removal system.
AB  - This study investigated the biosorption kinetics and equilibrium of cadmium,
      nickel and zinc by activated sludge from a biological nutrient removal (BNR)
      process. A series of batch experiments with different initial metal
      concentrations were conducted to determine the metal removal in BNR sludge. The
      harvested sludges were from a continuous-flow anaerobic-anoxic-oxic (A2O) system
      operated under a 10 days of sludge retention time. Batch tests were specially
      designed to isolate the precipitation effects of metal ions in solution so as to
      compare the isotherm constants of biosorption with and without precipitation
      isolation. Experimental results revealed that BNR sludge exhibited two stages of
      biosorption, i.e., passive and then active uptake, for all three metals. The
      biosorption kinetic data of three tested metals can be effectively simulated by
      pseudo-second-order rate equations. Besides, the biosorption isotherm showed that
      metal biosorption behavior was statistically in agreement with the Freundlich
      model. The capacity constants k of the Freundlich model for Cd, Ni and Zn are
      0.50, 0.23 and 0.41; the affinity constants 1 / n are 0.96, 0.81 and 0.31,
      respectively. Additionally, precipitation behaviors of metals obviously should be
      carefully examined during biosorption batch tests with activated sludge;
      otherwise the biosorption effect could be significantly overestimated.

PMID- 17500321
TI  - Lower heating value dynamics during municipal solid waste bio-drying.
AB  - In agreement with the new European Union directives concerning the valorization
      of materials and energy recovery, Municipal Solid Waste (MSW) management is, in
      general based on an integrated approach characterized by a combination of
      different treatment processes. The bio-mechanical treatment (BMT) of MSW is an
      increasing option in Europe either as a pre-treatment before landfilling or as a
      pre-treatment before combustion. In this context the research on the bio-drying
      process is not fully developed. In the present paper the Lower Heating Value
      (LHV) dynamics during MSW bio-drying has been assessed. Measurements were made
      using a pilot scale bio-dryer that allows the recording of data as air flow,
      temperature (at the entrance, at the exit and inside the waste), and weight loss.
      An initial characterization of the MSW completes the input data. Results give
      information on the dynamics of the main process parameters (humidity, volatile
      solids, ammonia, Lower Heating Value) and also of additional parameters.

PMID- 17500323
TI  - A record of healthcare reform.

PMID- 17500322
TI  - Mechanical sludge disintegration: providing an alternative carbon source for
      nutrient removal.
AB  - The primary driver for efficient biological nutrient removal (BNR) in activated
      sludge treatment is the sufficient supply of soluble carbon. Several methods have
      been proposed to increase available carbon sources and enhance BNR. This study
      examines the effect of ultrasonic equipment and mechanical disintegration
      technologies on surplus activated sludge (SAS), to release additional soluble
      chemical oxygen demand (SCOD) and volatile fattty acids (VFA), as a carbon food
      source for BNR. A laboratory sonicator with a maximum power of 550W, a 3KW SONIX
      radial horn and a deflaker declared to be used in the paper industry were
      investigated. All caused significant release of SCOD, up to 48 fold. The maximum
      concentration of VFA reached (from 0-1 mg 1(-1)), was 530 mg 1(-1). To assess the
      likely impact to BNR, batch (21) anaerobic lab tests examining the use of
      disintegrated sludge on phosphorus and nitrogen removal were completed.
      Phosphorus removal was estimated by observing the phosphate release under
      anaerobic conditions and up to 460% more release was observed relative to
      controls. In addition, denitrification rates were improved by over 106%.
      Ultrasonic and mechanical disintegration technologies have been shown to release
      soluble carbon for BNR, with subsequent laboratory nitrogen and phosphorus
      removal efficiencies observed to be comparable to acetate.

PMID- 17500324
TI  - Reinventing performance evaluations.

PMID- 17500325
TI  - Building a new future together.

PMID- 17500326
TI  - The community health center perspective.

PMID- 17500327
TI  - Integrated care at Paxton House.

PMID- 17500328
TI  - Working together to address an urgent need.

PMID- 17500329
TI  - Benchmarking blossoms in the Garden State.

PMID- 17500330
TI  - Vista's limited impact.

PMID- 17500331
TI  - Examining chemical dependency providers' IT needs.

PMID- 17500332
TI  - A large court system tackles a huge problem.

PMID- 17500333
TI  - Treatment with a feminine touch.

PMID- 17500334
TI  - Ensure staff sign on and patients sign off.

PMID- 17500335
TI  - EMRs and database structures.

PMID- 17500337
TI  - Our time to lead.

PMID- 17500336
TI  - Moving beyond our EHR phobia.

PMID- 17500338
TI  - Teaching the past to guide the future.

PMID- 17500339
TI  - [Risk of acute hepatic insufficiency in children due to chronic accidental
      overdose of paracetamol (acetaminophen)].
AB  - Two girls aged 4 and 3 years, respectively, experienced acute liver failure due
      to accidental ingestion of supratherapeutic doses of paracetamol (90 mg/kg/day or
      more). Recognition of chronic paracetamol intoxication as a cause of acute
      hepatic failure is often delayed. It is important to consider the possibility of
      paracetamol-induced hepatotoxicity because many patients will recover if treated
      with N-acetylcysteine, as did both of these children. Patients with acute liver
      failure due to chronic paracetamol intoxication present with very high
      transaminase levels (> 4000 U/l), disproportionately low total bilirubin levels
      (< 200 micromol/l) and often hypoglycaemia.

PMID- 17500340
TI  - [The increased availability of self-tests for medical analyses].
AB  - A marked increase in the availability of diagnostic tests for use at home has
      been observed in recent years. There are regulations concerning the development
      and application of these tests. The question whether the increased use of self
      tests is a positive or negative development cannot be answered easily. In some
      cases serious diseases may be detected in people who are reluctant to consult a
      physician. In other cases false negative test results may delay necessary
      treatment. Further exploration of the use, sensitivity, specificity, benefits and
      harms of specific tests is warranted.

PMID- 17500341
TI  - ['The old man's friend': differences between The Netherlands and the United
      States with regards to decision-making for the treatment of pneumonia in nursing
      home patients with dementia].
AB  - Lower respiratory-tract infections are a leading cause of death in frail elderly
      patients. A comparative study of nursing home patients with dementia in The
      Netherlands and the United States found a difference in attitudes regarding the
      treatment of pneumonia. Specifically, treatment regimens were far more aggressive
      in the United States than in The Netherlands for patients with severe illness.
      Antibiotics were withheld in 56% of these patients in The Netherlands compared
      with 15% in the United States. Despite the different treatment approaches,
      adjusted mortality rates were similar. In The Netherlands, geriatricians and
      family members of patients with dementia have become aware of the potentially
      harmful effects of the aggressive treatment approaches that are often part of
      professional treatment protocols, particularly in patients for whom palliative
      care is more appropriate.

PMID- 17500342
TI  - [Epigenetic processes in malignant transformation: the role of DNA methylation in
      cancer development].
AB  - Defects in DNA that activate oncogenes or inactivate tumour-suppressor genes are
      regarded as a crucial step in tumour development. Understanding the processes
      that modulate gene activity, the so-called epigenetic processes, is gaining
      importance in the search for factors responsible for uncontrolled cell growth.
      Cell proliferation is determined by epigenetic and genetic processes. Abnormal
      patterns of methylation and other epigenetic processes, such as acetylation,
      nucleosome formation and compact chromatin structure, can suppress transcription
      and inactivate tumour-suppressor genes. Methylation status is a promising
      biomarker for malignancy because the process is not patient-specific, it occurs
      at an early stage oftumour development and may precede morphological changes.

PMID- 17500343
TI  - [Diagnostic image (320). A new mother with opisthotonus and extensor spasms].
AB  - A 21-year-old woman was admitted to a rural hospital in Tanzania after a home
      delivery one week before. She had signs of general body rigidity due to maternal
      tetanus.

PMID- 17500344
TI  - [Treatment of pneumonia in nursing home residents with severe dementia: for
      residents with poor prognosis, a more reserved approach in The Netherlands and
      more active treatment in the United States].
AB  - OBJECTIVE: To describe differences in the treatment of pneumonia and in the
      association of treatment with prognosis in Dutch and American nursing home
      patients with late-stage dementia. Design. Prospective studies in The Netherlands
      and the American state of Missouri. METHOD: In 61 Dutch nursing homes and 36 in
      Missouri, severely demented patients with pneumonia were included in the periods
      October 1996-July 1998 and August 1995-September 1998 respectively. Data was
      collected on their state of health, comorbidity, symptoms of pneumonia and
      treatment aspects such as antibiotic use, hospital admission and relief of
      symptoms. Comparisons were made between treatments in both countries and between
      groups of patients with a similar probability of mortality within 2 weeks.
      RESULTS: A total of 328 Dutch and 280 American patients were selected.
      Antibiotics were more frequently withheld in The Netherlands (in 33% of patients)
      than in Missouri (24%). Differences in antibiotic use were more pronounced in
      patients with a poor prognosis (56% versus 15%). Dutch patients were more
      frequently dehydrated but were less likely to receive rehydration therapy than
      American patients, with a larger difference in patients with a poor prognosis (2%
      versus 63%). Treatments to relieve symptoms that were provided more often in
      patients with a poor prognosis (in 20-26%) were: oxygen (both countries), and in
      The Netherlands also opiates, and hypnotics, sedatives or anxiolytics.
      CONCLUSION: In The Netherlands, curative treatment was frequently withheld in
      patients with severe dementia and pneumonia, and even more frequently when the
      prognosis was poorer. Conversely, treatment in Missouri was more active in
      patients with a poor prognosis. Despite more frequent palliative treatment goals
      in The Netherlands, treatments to relieve symptoms were provided infrequently and
      inconsistent with this approach. These insights may be helpful for decision
      making in the treatment of pneumonia in patients with severe dementia.

PMID- 17500345
TI  - [Corneal melting after ocular surgery in patients with auto-immune disorders].
AB  - Two women aged 78 and 74 years respectively, both with dry eyes due to underlying
      auto-immune disorders, presented after uncomplicated cataract surgery with
      immunostromal corneal ulceration. Intensive topical lubrication combined with
      systemic immunosuppressants were necessary to control the corneal melt. Dry eyes
      are a frequently-encountered problem among patients with rheumatoid disorders and
      increase the risk of corneal melting. Auto-immune related corneal melting can
      occur spontaneously or after ocular surgery, it threatens visual acuity and
      ocular integrity and may be associated with systemic vasculitis. When treating
      patients with rheumatoid disorders, the presence of dry eyes and the accompanying
      risk of serious complications need to be ascertained. In patients at risk, pre
      operative preventive measures to suppress any underlying systemic disorders and
      improve the ocular environment are necessary. When corneal melting is diagnosed,
      aggressive topical therapy combined with systemic immunosuppressants is
      indicated.

PMID- 17500346
TI  - [A brief history of the inguinal hernia operation in adults].
AB  - Late into the 19th century, treatment for inguinal hernias consisted of
      repositioning the hernia with trusses or using 'softening agents' such as warm
      herbal baths and moist bandages. Surgical resection or cauterisation, often
      combined with hemicastration, was only considered for cases ofstrangulated hernia
      that could not be repositioned. Bassini (1844-1924) is credited with developing
      the precursor to the modern inguinal hernia operation at the end of the 19th
      century. Bassini's essential discovery was that the transverse fascia plays a key
      role in the pathophysiology of inguinal hernias. Bassini's operation, consisting
      of complete incision of the transverse fascia and reconstruction of the inguinal
      floor, was considered the gold standard for nearly a century. One problem with
      the conventional Bassini operation was the tension applied to tissues, which led
      to a high rate of recurrence. Although Bassini's operation has now become
      obsolete, current surgical approaches still centre on fortification of the
      inguinal floor. This tension-free repair now uses synthetic mesh that is
      positioned using an open anterior approach, laparoscopic surgery, or a
      preperitoneal technique.

PMID- 17500347
TI  - [The basic biomedical subjects are of undiminished importance in the training of
      medical doctors].
AB  - The contemporary physician is not merely a professional who is trained in the
      recognition of clinical syndromes and the application of evidence-based medicine.
      A good understanding of the basic biomedical sciences is necessary to comprehend
      what is wrong with a patient and what form of treatment is the most appropriate,
      especially if a disease manifests itself in an unfamiliar way.

PMID- 17500348
TI  - [The basic biomedical subjects are now less important in the training of medical
      doctors].
AB  - Medical doctors that neglect the roles of communicator, team worker, organizer
      and professional can be expected to perform inadequately. The content of the
      training of medical doctors should be reconsidered. A selection should be made of
      the biomedical sciences that are required during the training for later medical
      practice. Thus, these basic sciences should, in part, make way for social
      sciences to ensure the development of team skills.

PMID- 17500349
TI  - [Late postpartum eclampsia].

PMID- 17500350
TI  - [Chickenpox: sufficient reasons for the introduction of vaccination].

PMID- 17500351
TI  - Mortality in insureds with complete right or left bundle branch block.
AB  - BACKGROUND: On May 1, 1954, a prospective mortality study was instituted in the
      Medical Department of the New England Mutual Life Insurance Company for all
      persons on whom an electrocardiogram (ECG) was made. Details were coded on an 80
      column, mark-sense punched card for the ECG interpretation, for clinical
      findings, and for demographic/insurance data. RESULTS: Mortality is based on the
      experience of 231 policy-holders with complete right bundle branch block (RBBB)
      and 45 policyholders with complete left bundle branch block (LBBB). These were
      drawn from 28,687 interpretation records 1954-1966, if there was some follow-up
      (FU) exposure between 1954 and 1975. Mortality data are for all ages and all
      durations combined. In cases with associated rated cardiovascular (CV)
      impairment, there were 22 observed vs 7.72 expected deaths in RBBB, and 6
      observed vs 2.72 expected deaths in LBBB. Exposures and deaths were smaller when
      there was no rated CV impairment associated with the ECG abnormality: 11 observed
      vs 8.11 expected deaths in RBBB, and 3 observed vs 1.78 expected deaths in LBBB.
      CONCLUSIONS: In complete RBBB, excess mortality was significant at the Poisson
      95% confidence level when a rated CV impairment was associated with the RBBB, but
      the excess was minimal and not significant when the RBBB was essentially an
      isolated finding with no associated CV impairment. In LBBB the numbers of deaths
      were too few to permit even a 90% confidence level of significance when there was
      an associated CV impairment (the 2.72 expected deaths were just above the lower
      limit of 2.6 deaths at the 90% level).

PMID- 17500352
TI  - Cutaneous lymphomas.
AB  - This paper is a written presentation of a workshop held at the American Academy
      of Insurance Medicine 115th Annual Meeting held in October 2006 in San Antonio,
      Texas. Cutaneous lymphomas, though not common, are encountered several times per
      year in insurance medicine. Significant advances have been made in the diagnosis
      and classification of lymphomas. This paper serves as a general primer to help
      classify and assess mortality risk of various cutaneous lymphomas.

PMID- 17500353
TI  - Mortality and prescription drug use: an analysis using the CHS limited access
      data.
AB  - Ongoing interest in the use of drug profiles derived from pharmacy benefit
      program databases continues as a tool for life insurance risk assessment. The
      Cardiovascular Health Study (CHS) limited access data may be another way to
      explore the association between the number of prescriptions used by an
      individual, classified by drug class, and the risk of death. The CHS captured
      medication use of participants at baseline. An exploratory analysis, using Cox
      proportional hazards regression, was performed to assess a simple score based on
      the number of drug classes used and the hazard of death over the 8 years of
      follow up available (n=5795). When adjusted for gender, current smoking status,
      and age, the hazard ratio (HR) of death associated with this score was 1.19 (95%
      CI: 1.15-1.22). Use of calcium supplements and hormone therapy were associated
      with favorable mortality risk. As expected, insulin, oral agents for diabetes,
      CHF therapy, and oral steroids were associated with the greatest increase of
      mortality risk (49%-101%). A score was also created by summing only the 10
      significant drug classes derived from a stepwise model. The HR of death
      associated with this "significant sum" was 1.37 (95% CI: 1.32-1.44), adjusted for
      gender, age, and current smoking status. This exploratory analysis suggests that
      a drug score based on a simple sum of prescription drug classes used could be a
      useful predictor of mortality in an elderly (aged 65 and over) population.

PMID- 17500354
TI  - The gang of four: how does the growth of life settlements affect the life
      insurance industry?

PMID- 17500355
TI  - A 51-year-old male with arteries of a 68-year-old--carotid artery intima-media
      thickness and cardiovascular risk.

PMID- 17500356
TI  - The skinny on wide QRS complexes.
AB  - The presence of widened QRS complexes in a life insurance applicant's
      electrocardiogram may be due to such things as an intraventricular conduction
      defect, preexcitation syndrome, left ventricular hypertrophy, ventricular pacing,
      hyperkalemia and a ventricular rhythm. Clinical information and basic
      electrocardiogram interpretation techniques can usually narrow the differential
      diagnosis. Risk assessment of intraventricular conduction defects requires
      identification of typical electrocardiographic patterns followed by a careful
      search for additional electrocardiographic features, which may indicate the
      presence of more extensive conducting system disease and/or coexisting disease
      affecting the myocardium.

PMID- 17500357
TI  - Acoustic neuroma and radiosurgery.

PMID- 17500358
TI  - Dermatomyositis.
AB  - Dermatomyositis is an inflammatory disease with an unknown cause affecting
      primarily the skin and muscles with an increased risk of malignancy.

PMID- 17500359
TI  - Identification and determination of the major constituents in traditional Chinese
      medicinal plant Polygonum multiflorum thunb by HPLC coupled with PAD and ESI/MS.
AB  - An HPLC-PAD-MS method has been developed for the qualitative and quantitative
      analysis of the major chemical constituents in Polygonum multiflorum Thunb.
      Chromatographic separation was conducted on an Alltima C18 column using
      water:acetonitrile:acetic acid as the mobile phase. Altogether nine compounds of
      various classes, including stilbene glucosides, anthraquinone glucosides and
      anthraquinone derivates, were identified by online ESI/MS. Their identities were
      ascertained by comparison with data derived from the literature and/or standard
      compounds. Five components were quantified by HPLC-PAD and the method was fully
      validated. All the linear regressions were acquired with R2 > 0.99 and the
      quantification limits (with a signal-to-noise ratio of 3) ranged from 0.63 and
      1.57 ng. Repeatability was evaluated by intra- and inter-day assays and RSD value
      was within 2.47%. Recovery studies for the quantified compounds were found to be
      within the range 96.32-102.53% with RSD less than 2.35%. The overall procedure is
      rapid and reproducible and is considered suitable for qualitative and
      quantitative analysis of a large number of samples.

PMID- 17500360
TI  - The skimmiwallinols--minor components of the epicuticular wax of Cocos nucifera.
AB  - Four new skimmiwallinol derivatives, isoskimmiwallinol acetate (4),
      skimmiwallinol acetate (5), isoskimmiwallinone (6) and skimmiwallinone (7), along
      with the previously isolated major components isoskimmiwallin (2) and
      skimmiwallin (3), have been found in the wax extract of pinnae from Cocos
      nucifera. Metabolites 4 and 5 were obtained as an inseparable mixture and
      identified by analysis of spectroscopic data and chemical correlation with 2 and
      3, respectively. Metabolites 6 and 7 were identified by GC co-injection with the
      corresponding synthetic derivatives prepared from 4 and 5.

PMID- 17500361
TI  - Isolation and characterisation of procyanidins from Rumex obtusifolius.
AB  - An acetone:water (7:3) extract obtained from the leaves of Rumex obtusifolius was
      fractionated into procyanidin oligomer and polymer fractions using a linear
      gradient and a simple step method on Sephadex LH-20. The chemical characteristics
      of the procyanidin fractions were studied by 13C-NMR spectroscopy, acid-catalysed
      degradation in the presence of benzyl mercaptan, matrix-assisted laser
      desorption/ionisation time-of-flight (MALDI-TOF) MS and electrospray ionisation
      (ESI) MS. The 13C-NMR showed that the polymer fraction consisted predominantly of
      procyanidin polymers, some with galloyl groups attached. The thiolysis reaction
      products indicated a mean degree of polymerisation (DP) of 4.3 for the step
      method, and a range of 2.3-8.2 mean DP for the gradient fractionation, with
      epicatechin as the most abundant flavan-3-ol extension unit, while the terminal
      units consisted of equal proportions of catechin, epicatechin and epicatechin
      gallate. Singly charged ions observed in MALDI-TOF/MS showed a range of
      oligomeric procyanidins and their polygalloyl derivatives. These species (in the
      range DP 2-7) were also observed by ESI/MS but the spectra were more complex due
      to overlapping multiply charged ions. Isolation of oligomers from the Sephadex LH
      20 fraction by chromatography on polyamide and C18 yielded B1, B2, B3 and B7
      dimers, an A-type trimer and a B2 3,3'-O-digallate.

PMID- 17500362
TI  - Simultaneous determination of total hypericin and hyperforin in St. John's wort
      extracts by HPLC with electrochemical detection.
AB  - An analytical procedure was developed for the simultaneous determination of total
      hypericin (protopseudohypericin, pseudohypericin, protohypericin and hypericin)
      and hyperforin in Hypericum perforatum (St. John's wort) extracts and its
      preparations. The determination of total hypericin and hyperforin in one step was
      achieved by exposing the samples to artificial daylight in amber glass vials.
      This procedure allows both the photoconversion of the protoforms into the
      appropriate hypericins and the protection of the photosensitive hyperforin. For
      quantification, an HPLC method with electrochemical detection was applied. As an
      example of the application of the principle, two preparations containing St.
      John's wort were assayed.

PMID- 17500363
TI  - A rapid TLC autographic method for the detection of glucosidase inhibitors.
AB  - A new bioautographic assay suitable for the localisation of beta-glucosidase
      inhibitors present in a complex matrix is described. Enzyme activity was detected
      using esculin as the substrate to produce esculetin, which reacts with ferric ion
      to form a brown complex.

PMID- 17500364
TI  - Isolation of chlorogenic acids and their derivatives from Stemona japonica by
      preparative HPLC and evaluation of their anti-AIV (H5N1) activity in vitro.
AB  - Two chlorogenic acids and five chlorogenic acid derivatives were simultaneously
      separated and purified from Stemona japonica by preparative high-performance
      liquid chromatography. Five of the collected compounds were over 95% pure while
      the other two compounds were over 90% pure. Their structures were elucidated as 3
      O-feruloylquinic acid (1), 4-O-feruloylquinic acid (2), methyl 3-O
      feruloylquinate (3), methyl 5-O-caffeyolquinate (4), methyl 4-O-feruloylquinate
      (5), ethyl 3-O-feruloylquinate (6) and the new compound ethyl 4-O-feruloylquinate
      (7) by UV, NMR and ESI-MS. All compounds were obtained from Stemona species for
      the first time, however compounds 6 and 7 are believed to be artefacts from the
      ethanol extraction. The anti-AIV (H5N1) activities were evaluated by Neutral Red
      uptake assay. Compounds 3 and 4 exerted moderate inhibitory effect against AIV
      (H5N1) in vitro.

PMID- 17500365
TI  - Analysis of polyphenolic compounds and radical scavenging activity of four
      American Actaea species.
AB  - A reversed-phase high-performance liquid chromatography (RP-HPLC) method with
      diode array detection has been developed for analysis of the major polyphenols in
      the roots and rhizomes of black cohosh (Actaea racemosa), an important botanical
      dietary supplement for women's health, and three closely related American Actaea
      species, A. rubra, A. pachypoda and A. podocarpa. The method was validated with
      respect to sensitivity, linearity, precision, accuracy and recovery. The total
      content of eight major polyphenols in the dried root and rhizome of the four
      species was determined to be from 0.36 to 2.92% (w/w). The antioxidant activities
      of Actaea extracts and polyphenolic compounds isolated from A. racemosa were
      evaluated on 1.1-diphenyl-2-picrylhydrazyl (DPPH) free radicals scavenging assay.
      The radical scavenging activity of the Actaea extracts correlates to their
      polyphenolic composition. This validated HPLC method can be used to distinguish
      A. racemosa from the other major American Actaea species based on this study.

PMID- 17500366
TI  - TLC-densitometric analysis of artemisinin for the rapid screening of high
      producing plantlets of Artemisia annua L.
AB  - A simple TLC-densitometric technique has been developed for the rapid and
      accurate analysis of artemisinin in a large number of Artemisia annua plantlets
      cultured in vitro. This new analytical method is based on the structural
      conversion of artemisinin on a silica gel layer by ammonia vapour to form 10
      azadesoxyartemisinin, a chromophore-containing compound (lambdamax 320 nm) that
      can be detected by UV-based TLC densitometry. The TLC system was evaluated
      quantitatively in terms of product stability, precision, accuracy and
      calibration. Good linearity was obtained in the range of 0.01-0.12 microg
      artemisinin. The technique appeared to be accurate and sensitive as compared with
      the complicated pre-column reaction-HPLC technique. Among 90 samples of A. annua
      plantlets, the artemisinin content in the leaves appeared to be highly variable,
      ranging from 0.02 to 0.67% w/w dry weight. These results demonstrate that
      densitometric TLC can be a cheap and simple technique for the accurate screening
      of high-artemisinin-producing plants.

PMID- 17500367
TI  - Analysis of the essential oil from the roots of Eupatorium cannabinum subsp.
      corsicum (L.) by GC, GC-MS and 13C-NMR.
AB  - Eupatorium cannabinum subsp. corsicum (L.) is an endemic subspecies from the
      island of Corsica. The essential oil from the roots of this aromatic plant has
      been studied by GC, GC-MS and by 13C-NMR. In contrast to the essential oil from
      the aerial parts, which is dominated by hydrocarbon compounds (76.9%) and
      particularly by sesquiterpene components (43.3%), the essential oil from the
      roots was characterized by a high content of oxygenated compounds (61.0%),
      particularly oxygenated monoterpenes (54.0%). In the root oil, 106 components
      were identified representing 96.1% of the total amount. This oil was dominated by
      the monoterpenes esters (33%), the major components of which were neryl
      isobutyrate (17.6%), thymyl methyl oxide (15.1%), delta-2-carene (14.5%) and beta
      pinene (5.7%). Aromatic esters, nerol derivatives (esters and diesters) and a
      benzofuran were investigated by GC-MS using different ionization modes including
      electron impact ionization, and positive- and negative-chemical ionization. These
      components have not previously been reported in the essential oil of aerial parts
      of E. cannabinum from Corsica island.

PMID- 17500368
TI  - Seasonal variations in the isoflavonoids of radix Puerariae.
AB  - The variations in isoflavonoid content in Radix Puerariae, the root of Pueraria
      lobata (Wild) Ohwi, have been examined in order to determine the optimum time to
      harvest the herb. Total isoflavonoid contents have been analysed by a UV
      spectrophotometric method whilst HPLC with photodiode array detection has been
      used to monitor the contents of seven major individual isoflavonoids, namely, 3'
      hydroxypuerarin, puerarin, 3'-methoxypuerarin, daidzin, genistin, formononetin-7
      glucoside and daidzein. Ninety-six samples of Radix Puerariae of different ages
      and harvested in different months were collected and analysed. The results
      clearly showed that 3-year-old roots harvested in January have the highest yields
      of isoflavonoid compounds. Moreover, the results obtained by both methods have a
      strong correlation. This suggested that the simple and fast UV spectrophotometric
      method could be used for monitoring the phytochemical quality of Radix Puerariae.

PMID- 17500369
TI  - Chemical investigation of Phyllanthus reticulatus by HPLC-SPE-NMR and
      conventional methods.
AB  - Eight compounds, including two flavonoid glycosides, were isolated from the
      butanol-soluble fraction of the methanolic extract of the leaves of Phyllanthus
      reticulatus by conventional methods. A polyphenol rich fraction, obtained by
      Sephadex LH-20 fractionation, was also studied using an HPLC-SPE-NMR technique
      leading to the characterization of six compounds including three additional
      flavonoid glycosides. The latter approach used only 1 mg of samples,
      theoretically equivalent to 0.3 g of dry leaves. This study demonstrates that
      HPLC-SPE-NMR is very useful for thorough chemical investigation and also offers
      the advantages of saving time, plant materials and consumables over more
      conventional methods.

PMID- 17500370
TI  - Current awareness in phytochemical analysis.

PMID- 17500371
TI  - Medicare on my mind.

PMID- 17500372
TI  - What is your diagnosis? Uncombable hair syndrome (pili trianguli et canaliculi).

PMID- 17500373
TI  - What's eating you? Flat rock scorpion (Hadogenes granulatus).

PMID- 17500374
TI  - Childhood vitiligo.
AB  - Vitiligo is a depigmentation disorder resulting from autoimmune destruction of
      cutaneous melanocytes. The psychosocial ramifications of this often disfiguring
      disease can be substantial. Half of the patients with vitiligo experience disease
      onset in childhood. Although largely similar to the disease in adults, pediatric
      vitiligo does have differences in epidemiology, associations, and treatment. We
      review vitiligo as it relates to the pediatric population, emphasizing key
      differences with adults and the latest treatment advances.

PMID- 17500375
TI  - Current and emerging therapeutic modalities for hyperhidrosis, part 2: moderately
      invasive and invasive procedures.
AB  - Hyperhidrosis (HH) hinders patient quality of life and causes the secondary
      effect of excess cutaneous sweat. Treatment modalities include conservative and
      noninvasive therapies such as topical agents and iontophoresis. This article
      reviews moderately invasive and invasive procedures, such as botulinum toxin,
      curettage, and endoscopic thoracic sympathectomy (ETS), and compares their
      advantages and disadvantages in safety and efficacy.

PMID- 17500376
TI  - Lupus pernio.

PMID- 17500377
TI  - Actinobacillus actinomycetemcomitans isolated from a case of cutaneous
      botryomycosis.
AB  - Cutaneous botryomycosis is an uncommon chronic suppurative bacterial skin
      infection that can mimic a fungal infection both clinically and
      histopathologically. Causative bacteria, most commonly Staphylococcus aureus,
      aggregate to form characteristic granules. We report the case of a 52-year-old
      black man who developed cutaneous botryomycosis of the hand following trauma.
      Routine bacterial cultures grew S aureus and Actinobacillus
      actinomycetemcomitans, a fastidious gram-negative bacillus known to cause
      periodontal disease, endocarditis, and actinomycosislike soft tissue infections.
      Despite culture-proven eradication of S aureus with long-term appropriate
      antibiotic therapy, the lesion, resolved only after fluoroquinolone treatment
      directed against A. actinomycetemcomitans, suggesting that A.
      actinomycetemcomitans was of etiologic significance.

PMID- 17500378
TI  - Multiple microcystic adnexal carcinomas.
AB  - Microcystic adnexal carcinoma (MAC) is a relatively uncommon adnexal neoplasm
      that can demonstrate locally aggressive behavior; rare instances of metastatic
      lesions have been reported. We report a case of a 34-year-old black man with
      multiple primary MACs.

PMID- 17500379
TI  - Epidermodysplasia verruciformis occurring in a patient with human
      immunodeficiency virus: a case report.
AB  - Epidermodysplasia verruciformis (EV) is an uncommon dermatosis associated with
      human papillomavirus (HPV) infection in association with defects in cell-mediated
      immunity. Malignant transformation to squamous cell carcinoma has been associated
      with lesions caused by HPV-5, HPV-8, and HPV-14. Clinically, the disease may be
      confused with verruca plana, seborrheic keratosis, and pityriasis versicolor. We
      present an unusual case of EV occurring in a human immunodeficiency virus (HIV)
      positive man and discuss the clinical and histologic findings. Clinically, the
      patient had 1- to 3-mm hypopigmented smooth macules covering the entire body.
      Histopathologic examination of the skin biopsy results demonstrated enlarged
      keratinocytes with prominent blue-gray cytoplasm and clumping of keratohyalin
      granules within the granular layer of the epidermis. Although EV typically is
      viewed as a disease of childhood, sometimes presenting in patients with a family
      history of the disease, it rarely may be seen in immunocompromised adults.

PMID- 17500380
TI  - Cumulative irritation potential among metronidazole gel 1%, metronidazole gel
      0.75%, and azelaic acid gel 15%.
AB  - Topical therapy for rosacea aims to reduce inflammatory lesions and decrease
      erythema but can carry side effects such as stinging, pruritus, and burning.
      Metronidazole and azelaic acid gel 15% are U.S. Food and Drug Administration
      approved for the treatment of rosacea. The current study was conducted to assess
      the cumulative irritation potential of 2 formulations of metronidazole 0.75% gel
      and 1% gel--and azelaic acid gel 15% over 21 days (N=36). Results of this study
      demonstrated a significantly greater poten tial for irritation from azelaic acid
      compared with metronidazole gel 0.75% (P < .0001), which had significantly
      greater potential for irritation compared with metronidazole gel 1% (P = .0054).
      Metronidazole gel 1% had a similar profile to white petrolatum.

PMID- 17500381
TI  - Etanercept improves psoriatic arthritis patient-reported outcomes: results from
      EDUCATE.
AB  - Experience Diagnosing, Understanding Care, and Treatment With Etanercept
      (EDUCATE) is a multicenter, phase 4, 24-week, open-label study of the safety and
      efficacy of etanercept therapy in patients with psoriatic arthritis (PsA) in
      routine dermatologic practice. We present data on patient-reported outcomes
      (PROs) from EDUCATE, which demonstrate that subjects with PsA achieved clinically
      meaningful improvements in both skin- and joint-related PROs after 24 weeks of
      treatment.

PMID- 17500382
TI  - Maintenance of certification in U.S. otolaryngologists: an update.

PMID- 17500383
TI  - Sarcoidosis presenting as a solitary parotid mass: an uncommon but real
      diagnostic challenge.

PMID- 17500384
TI  - Epidermolysis bullosa.

PMID- 17500385
TI  - Endoscopic view of an infected concha bullosa.

PMID- 17500386
TI  - Vocal process granuloma.

PMID- 17500387
TI  - Traumatic fracture callus.

PMID- 17500388
TI  - Glomus tympanicum tumor.

PMID- 17500389
TI  - Surgical rehabilitation for primary laryngeal amyloidosis.

PMID- 17500390
TI  - Gastric carcinoma.

PMID- 17500391
TI  - Bilateral subglottic cysts in an infant treated with CO2 laser marsupialization.

PMID- 17500392
TI  - Direct deposit for reimbursements.

PMID- 17500393
TI  - Embryonal rhabdomyosarcoma of the temporal bone.
AB  - The most common soft-tissue sarcoma in infants and children is rhabdomyosarcoma.
      The head and neck is the most common site of involvement; temporal bone
      involvement has been seen in about 7% of reported cases. Multimodality therapy-
      surgery, multiagent chemotherapy, and radiotherapy-yields sufficiently good
      results. The author reports a case of embryonal rhabdomyosarcoma of the temporal
      bone with cranial nerve palsies and extension into the parapharyngeal space in a
      4-year-old boy. Despite surgery and chemotherapy, the patient died of his disease
      within 3 months of presentation.

PMID- 17500394
TI  - Cerebrospinal fluid otorrhea presenting in complicated chronic suppurative otitis
      media.
AB  - Since the introduction of antibiotics, the simultaneous occurrence of multiple
      intra- and extracranial complications in chronic suppurative otitis media (CSOM)
      has been uncommon. Such a combination is associated with high mortality and
      morbidity, especially in the pediatric age group. Cerebrospinal fluid (CSF)
      otorrhea presenting in CSOM is unusual and rare. To the best of our knowledge,
      only 19 cases of CSF otorrhea in complicated CSOM have been previously reported
      in the literature. Identifying the site of leak might require a high index of
      suspicion. Management of such a case could be challenging in terms of leak
      closure, disease clearance, and restoration of function. We report a new case of
      CSF leak in CSOM, and we describe our line of management. Even though CSOM is an
      uncommon indication for radical mastoidectomy today, such surgery might be
      necessary for these cases.

PMID- 17500395
TI  - A new method for closure of small to medium-size nasoseptal perforations.
AB  - This article describes a new method of repairing nasoseptal perforations. The
      surgical procedure involves rotating a composite transposition flap of mucosa and
      cartilage anchored at the posterior margin of the perforation. The focus of the
      repair is to preserve vascularity to the flap and thereby enhance the survival of
      the cartilage and mucosa. This method appears to be most suitable for repairing
      small to medium-size perforations. Early success has been promising and warrants
      a trial by others.

PMID- 17500396
TI  - Schwannoma of the nasal cavity.
AB  - Schwannomas are benign peripheral nerve sheath tumors that occur throughout the
      body. They may present as either solitary or multiple masses. They rarely occur
      in the nasal cavity. The diagnosis is often made only after histologic
      examination. Because these lesions are radioresistant, the preferred treatment is
      complete surgical excision. We present a new case of a schwannoma of the nasal
      cavity.

PMID- 17500398
TI  - Follicular dendritic cell sarcoma of the tonsil: a case report and literature
      review.
AB  - We describe a case of follicular dendritic cell sarcoma (FDCS) of the tonsil in a
      59-year-old woman. She was successfully treated with excision of the mass and
      postoperative radiation therapy. According to our review of the literature, only
      25 cases of extranodal FDCS in the head and neck have been previously reported,
      including only 10 cases that involved a tonsil. We briefly review these earlier
      reports, and we discuss the diagnosis and management of FDCS.

PMID- 17500397
TI  - Tongue erosions and diet cola.
AB  - We report the case of a 38-year-old woman who presented with a 10-year history of
      painful ulcerations on her tongue. She reported that she drank large quantities
      of diet cola and some orange juice daily and that she used cinnamon-flavored
      toothpaste and mouthwash nightly. Patch testing elicited positive reactions to
      balsam of Peru (a fragrance as well as a flavoring agent put in cola drinks that
      cross-reacts with orange juice) and cinnamic aldehyde. She was diagnosed with
      allergic contact dermatitis. She was put on a restricted diet and a fragrance
      free regimen, and her condition resolved.

PMID- 17500399
TI  - Tuberculous retropharyngeal abscess.
AB  - Chronic retropharyngeal abscess caused by tuberculosis is rare. It should be
      suspected in a person who presents with a destructive lesion of the vertebra and
      a retropharyngeal mass. Early diagnosis and treatment are necessary to prevent
      the serious complications of the disease. We present the case of a patient who
      came to our clinic with collapse of the C5-C6 vertebrae and retropharyngeal
      abscess. We were able to avoid any complications by initiating early surgical
      drainage and antituberculous therapy.

PMID- 17500400
TI  - Vocal fold deposits in macrophagic myofasciitis.
AB  - Macrophagic myofasciitis was first reported in 1998. This disease manifests as
      diffuse myalgia and chronic fatigue. Its pathophysiology has been traced to the
      presence of an aluminum adjuvant used in vaccines against hepatitis A and B virus
      and tetanus toxoid; the adjuvant aggregates at the site of injection. One-third
      of patients with macrophagic myofasciitis develop autoimmune disease. Vocal fold
      deposits have been described in autoimmune diseases such as sarcoidosis, systemic
      lupus erythematosus, multiple sclerosis, rheumatoid arthritis, Sjogren's
      syndrome, and Hashimoto's thyroiditis. We report what to the best of our
      knowledge is the first published case of vocal fold deposits in macrophagic
      myofasciitis.

PMID- 17500401
TI  - Tracheobronchial stenting in an infant with an anomalous right main bronchus.
AB  - Congenital anomalies of the right main bronchi have not been fully described.
      Bronchial anomalies are usually asymptomatic unless they coexist with other
      abnormalities. We describe a rare bronchial anomaly in a 2-month-old girl in
      which the right upper lobe, middle lobe, and lower lobe bronchi all originated at
      the same point as a result of a developmental teratogenic long right main
      bronchus and an absent bronchus intermedius. Furthermore, the left main bronchus
      contained a proximal segment of stenosis. This combination of anomalies, along
      with right upper lobe atelectasis and left-sided hyperinflation, resulted in a
      severe right mediastinal shift and respiratory distress. The mediastinum was
      returned to midline with endoscopic placement of an in-dwelling tracheobronchial
      stent into the left main bronchus. To the best of our knowledge, the specific
      developmental anomaly in our patient has not been previously described.

PMID- 17500402
TI  - When pariahs have good ideas.

PMID- 17500403
TI  - Structured settings. Novel techniques expand the nanotech tool kit.

PMID- 17500404
TI  - Codon spell check. Silent mutations are not so silent after.

PMID- 17500405
TI  - Motion pictures. HDTV broadcasters plan to get into mobile video.

PMID- 17500406
TI  - Escape from the nucleus. Ionization via quantum tunneling observed.

PMID- 17500407
TI  - Dialing in. Mobile phones target the world's nonreading poor.

PMID- 17500408
TI  - Microchips with heart. No batteries needed: pumps driven by heart cells.

PMID- 17500410
TI  - Bush's mistake and Kennedy's error.

PMID- 17500409
TI  - Food boom. Agricultural productivity sustains the U.S. economy.

PMID- 17500411
TI  - The road to clean energy starts here.

PMID- 17500413
TI  - The mystery of methane on Mars & Titan.

PMID- 17500412
TI  - Prime directive for the last Americans.

PMID- 17500415
TI  - Preventing blackouts.

PMID- 17500414
TI  - Chromosomal chaos and cancer.

PMID- 17500417
TI  - Carbon nanonets spark new electronics.

PMID- 17500416
TI  - South America's missing mammals.

PMID- 17500418
TI  - Eyes open, brain shut.

PMID- 17500419
TI  - A do-it-yourself quantum eraser.

PMID- 17500420
TI  - Directional sound. Psst... hey, you.

PMID- 17500421
TI  - Where is the universe expanding to?

PMID- 17500422
TI  - Forensic individualisation from biometric data.

PMID- 17500423
TI  - A pilot study to determine the background population of foreign fibre groups on a
      cotton/polyester T-shirt.

PMID- 17500424
TI  - Under-water scene investigation using ground penetrating radar (GPR) in the
      search for a sunken jet ski, Northern Ireland.

PMID- 17500425
TI  - The effect of bone marrow transplants on DNA profiles; a case example.

PMID- 17500426
TI  - Relationship between nephrologist care and progression of chronic kidney disease.
AB  - BACKGROUND: Since chronic kidney disease (CKD) affects 11% of the United States
      population, and its incidence is rising, experts recommend early referral to
      nephrologists in the hope that it may delay the onset of end-stage disease and
      improve survival. However, limitations in the capacity of currently practicing
      nephrologists may prevent widespread early referral. OBJECTIVE: To examine the
      relationship between disease progression and timing of nephrology referral. STUDY
      DESIGN AND DATA COLLECTION: We retrospectively identified 1,553 veterans at the
      Durham, North Carolina VA hospital between January 1998 and December 1999 who had
      CKD, defined as two outpatient serum creatinines > or = 1.4 mg/dL at least three
      months apart. Our endpoint was a composite of progression to the next CKD stage
      or death. We compared the time to the composite endpoint for each CKD stage and
      for early CKD (stages 1-3) to advanced CKD (stages 4 and 5) using a Cox
      proportional hazards model for two groups: those with primary care only (PCP
      only) and those with primary and nephrology care (nephrology). RESULTS: Ninety
      two percent had hypertension, 52% diabetes, 49% coronary artery disease, and 89%
      proteinuria. Angiotensin-converting enzyme inhibitors and anti-lipid medications
      were used by 52% and 39%, respectively. The median number of days spent in each
      CKD stage and the proportion of each groups reaching the composite endpoint are-
      stage 1: 1,149 days, 68% of the PCP-only group and 73% of the nephrology group;
      stage 2: 1,206 days, 60% and 65%; stage 3: 1,158 days, 69% and 63%; and stage 4:
      794 days, 86% and 72%. Adjusted survival curves for the composite endpoint were
      similar between the two groups for CKD stages 1 (HR 1.08 for nephrology versus
      PCP-only) and 2 (HR 1.20); however for CKD stages 3 (HR 0.80, p < 0.05) and 4 (HR
      0.75, p < 0.05), the nephrology group gained 316, 215, and 120 more days of
      progression-free survival, respectively. LIMITATIONS: The major limitation is
      difficulty accounting for unmeasured bias in specialty referrals. We were unable
      to analyze stage 5-to-dialysis due to the small number of individuals with the
      outcome. CONCLUSION: Our data suggest that an appropriate time for nephrology
      comanagement of patients with CKD may be stage 3; however, prospective studies
      are needed to clarify the role and timing of nephrology referral.

PMID- 17500427
TI  - Attitudes about tobacco policies among North Carolina parents.
AB  - BACKGROUND: While tobacco use reduction remains a major public health goal,
      little evidence exists on how citizens in North Carolina view policy issues
      related to tobacco control. This research examines attitudes toward tobacco
      policies among North Carolina parents. METHODS: Randomly selected North Carolina
      adults with a child living in his or her household were invited to participate in
      the Child Health Assessment and Monitoring Program (CHAMP) telephone survey. A
      sample of 3,973 parents or guardians was interviewed in 2005. Support for tobacco
      prevention and policies was analyzed by demographic characteristics. RESULTS: Of
      the 86% of initial respondents who were eligible to participate, 83% completed
      the 2005 CHAMP survey. Most parents in North Carolina (90.1%) support stronger
      policies for tobacco prevention. Parents also strongly support restrictions on
      tobacco in schools (85.6%) and recreational areas and fast food restaurants
      (83.9%). While many parents report being well prepared to talk to their children
      about smoking (97.6%) and report talking about the dangers of smoking monthly
      (84.7%), few report that their child currently smokes (3.9% of high school
      students and 0.6% of middle school students). LIMITATIONS: Because the CHAMP
      survey is telephone-based the results are limited to North Carolina parents who
      have a land-line telephone. CONCLUSIONS: Despite the states historical ties to
      tobacco, the overwhelming majority of North Carolina parents are in favor of
      stronger efforts at tobacco use prevention, including increased policy measures.
      These results suggest that prevention efforts should be expanded and that policy
      makers who take a stronger stance against tobacco will most likely receive broad
      support by North Carolina parents.

PMID- 17500428
TI  - Patient attitudes toward screening.
AB  - BACKGROUND: Physician organizations recommend screening for health care
      behaviors. Despite these recommendations, health care providers worry that
      questions on sensitive topics may not be accepted by their patients. To determine
      if there is a relationship between health care screening by providers and
      acceptance of that screening by patients, a survey of female patients was
      analyzed. METHOD: Two telephone surveys were conducted two years apart. Each was
      a cross-sectional sample of female patients over the age of 18 years who had been
      seen by their primary care provider (PCP) in the previous 12 months. Patients
      were asked if they had been screened for eight different health behaviors
      (exercise, smoking, use of alcohol or drugs, excessive stress, sexual functioning
      concerns, safety or violence in the home, guns in the home) in the past year.
      They were also asked about their attitudes toward screening for those behaviors
      by health care providers. Odds ratios were calculated for patients who both
      agreed that screening should occur and reported having been screened in the last
      year. RESULTS: 3,175 women were surveyed. There was high acceptance of routine
      screening for exercise (75%), smoking (72%), alcohol/drugs (68%), and stress
      (62%), but less for sexual functioning (40%), safety/violence (40%), or guns
      (23%). There was a higher likelihood of agreeing with routine screening if the
      patient reported having been screened in the past year: exercise (OR 2.3, 95% CI
      1.8-2.9), smoking (OR 1.6, 95% CI 1.3-1.9), alcohol/drugs (OR 2.3, 95% CI 1.9
      2.7), stress (OR 1.7, 95% CI 1.4-1.9), sexual functioning (OR 2.7, 95% CI 2.2
      3.4), safety/violence (OR 3.4, 95% CI 2.8-4.2), and guns (OR 4.4, 95% CI 3.4
      5.8). LIMITATIONS: Only women in established relationships with primary care
      providers were surveyed. The cross-sectional nature of the survey prevents
      determination of the causality of the relationship. CONCLUSION: Women who had
      been screened for a health behavior had greater acceptance of routine screening
      for that behavior. Although further research is needed to determine the casual
      relationship, providers should not worry about offending their patients when
      screening for sensitive health behaviors.

PMID- 17500429
TI  - Pandemic influenza: the critical issues and North Carolina's preparedness plan.

PMID- 17500430
TI  - Ethical guidelines for an influenza pandemic.

PMID- 17500431
TI  - Pandemic flu: why faith groups must care.

PMID- 17500432
TI  - Shall we gather by the river? Yes ... no ... maybe so....

PMID- 17500433
TI  - Eliminating injustice toward disadvantaged populations during an influenza
      pandemic.

PMID- 17500434
TI  - Manufacturing a flu vaccine.

PMID- 17500435
TI  - Likely ethical, legal, and professional challenges physicians will face during an
      influenza pandemic.

PMID- 17500436
TI  - Roles of hospitals during an influenza pandemic.

PMID- 17500437
TI  - All politics, pandemics, and plans are local.

PMID- 17500438
TI  - Pandemic influenza and the law: isolation, quarantine, and other legal tools for
      containing outbreaks.

PMID- 17500439
TI  - Business preparation for an influenza pandemic.

PMID- 17500440
TI  - Pandemic influenza: the consequences beyond public health.

PMID- 17500441
TI  - Ethics and avian flu.

PMID- 17500442
TI  - Influenza surveillance.

PMID- 17500443
TI  - James D. Bernstein Community Health Center.

PMID- 17500444
TI  - Point/counterpoint. Proton therapy is too expensive for the minimal potential
      improvements in outcome claimed.

PMID- 17500445
TI  - Energy imparted-based estimates of the effect of z overscanning on adult and
      pediatric patient effective doses from multi-slice computed tomography.
AB  - In the present study effective dose values normalized to computed tomography dose
      index measured free in air were calculated for adult, newborn, 1, 5, 10 and 15
      year old patients regarding scans of the head, chest, abdomen, pelvis, abdomen
      and pelvis, and trunk, using the energy imparted method. The effect of z
      overscanning on patient doses was accounted for, and normalized doses are
      provided for varying beam collimation, pitch and reconstruction slice width
      values. The contribution of overscanning depends on patient age, anatomic region
      imaged, acquisition and reconstruction settings. For a head scan it constitutes
      15% of the adult effective dose and 24% of the effective dose to a newborn but
      for an abdomen scan it may be as high as 58% for a newborn and 31% for an adult.
      The ratios of normalized pediatric doses relative to that for adults for helical
      scans depend not only on age but also on acquisition and reconstruction
      parameters, because of variations in the relative distance between the primary
      beam and the radiosensitive tissues/organs of the body. Regarding scans of the
      trunk, pediatric doses are up to a factor of 2.5 times higher compared to adult
      doses (abdominal scans), whereas for scans of the head up to a factor of 1.5.
      Increasing the pitch value of helical scans while maintaining the same effective
      mAs setting, and hence noise levels, leads to an increase in patient doses which
      depends on age, body region, scan and reconstruction parameters. The % difference
      between doses at pitch 1.5 and pitch 1 is more pronounced in the abdominal region
      (14% increase for adults) and in young patients (31% in a newborn and 18% in a 10
      year old patient) and it is minimal in head scans (4% increase in newborns and 1%
      in adults). If multiple body regions are to be imaged, doses to adults can be
      reduced by up to 15% and 36% to children by performing single long-range scans.
      Scanning adult patients at 100 kVp instead of 120 kVp, results in a 32% reduction
      in effective dose from head scans and 38% for scans of the torso. The
      corresponding reduction for a 5 year old patient is 31% for the head and 37% for
      the trunk. Due to the combined overbeaming and overscanning effect the 24 mm
      collimation is more dose effective in the head mode and the 12 mm collimation in
      the body mode. Provided data enable informed design of examination protocols,
      calculation of effective dose values and familiarization with the technical
      features of multi-detector technology.

PMID- 17500446
TI  - Predictive sensor based x-ray calibration using a physical model.
AB  - Many computer assisted surgery systems are based on intraoperative x-ray images.
      To achieve reliable and accurate results these images have to be calibrated
      concerning geometric distortions, which can be distinguished between constant
      distortions and distortions caused by magnetic fields. Instead of using an
      intraoperative calibration phantom that has to be visible within each image
      resulting in overlaying markers, the presented approach directly takes advantage
      of the physical background of the distortions. Based on a computed physical model
      of an image intensifier and a magnetic field sensor, an online compensation of
      distortions can be achieved without the need of an intraoperative calibration
      phantom. The model has to be adapted once to each specific image intensifier
      through calibration, which is based on an optimization algorithm systematically
      altering the physical model parameters, until a minimal error is reached. Once
      calibrated, the model is able to predict the distortions caused by the measured
      magnetic field vector and build an appropriate dewarping function. The time
      needed for model calibration is not yet optimized and takes up to 4 h on a 3 GHz
      CPU. In contrast, the time needed for distortion correction is less than 1 s and
      therefore absolutely acceptable for intraoperative use. First evaluations showed
      that by using the model based dewarping algorithm the distortions of an XRII with
      a 21 cm FOV could be significantly reduced. The model was able to predict and
      compensate distortions by approximately 80% to a remaining error of 0.45 mm (max)
      (0.19 mm rms).

PMID- 17500447
TI  - Influence of z overscanning on normalized effective doses calculated for
      pediatric patients undergoing multidetector CT examinations.
AB  - The purpose of this study was to evaluate the effect of z overscanning on
      normalized effective dose for pediatric patients undergoing multidetector
      computed tomography (CT) examinations. Five commercially available mathematical
      anthropomorphic phantoms representing newborn, 1-, 5-, 10-, and 15-year-old
      patients and the Monte Carlo N-Particle (MCNP, version 4C2) radiation transport
      code were employed in the current study to simulate pediatric CT exposures. For
      all phantoms, axial and helical examinations at 120 kV tube voltage were
      simulated. Scans performed at 80 kV were also simulated. Sex-specific normalized
      effective doses were estimated for four standard CT examinations i.e., head-neck,
      chest, abdomen-pelvis, and trunk, for all pediatric phantoms. Data for both axial
      and helical mode acquisition were obtained. In the helical mode, z overscanning
      was taken into account. The validity of the Monte Carlo results was verified by
      comparison with dose data obtained using thermoluminescence dosimetry and a
      physical pediatric anthropomorphic phantom simulating a 10-year-old child. In all
      cases normalized effective dose values were found to increase with increasing z
      overscanning. The percentage differences in normalized data between axial and
      helical scans may reach 43%, 70%, 36%, and 26% for head-neck, chest, abdomen
      pelvis, and trunk studies, respectively. Normalized data for female pediatric
      patients was in general higher compared to male patients for all ages, examined
      regions, and z overscanning values. For both male and female children, the
      normalized effective dose values were reduced as the age was increased. For the
      same typical exposure conditions, dose values decreased when lower tube voltage
      was used; for a 1-year-old child, for example, the effective dose was 3.8 times
      lower when 80 kV instead of 120 kV was used. Normalized data for the estimation
      of effective dose to pediatric patients undergoing standard axial and helical CT
      examinations on an multidetector CT system were calculated. This data was found
      to depend strongly on CT acquisition mode and exposure parameters as well as
      patient age and sex. The effective dose from a pediatric CT scan performed in
      axial mode was always considerably lower compared to the corresponding scan
      performed in helical mode, due to the additional tissue regions exposed to the
      primary beam in helical examinations as a result of z overscanning.

PMID- 17500448
TI  - BOLD fMRI integration into radiosurgery treatment planning of cerebral vascular
      malformations.
AB  - Functional magnetic resonance imaging (fMRI) is used to distinguish areas of the
      brain responsible for different tasks and functions. It is possible, for example,
      by using fMRI images, to identify particular regions in the brain which can be
      considered as "functional organs at risk" (fOARs), i.e., regions which would
      cause significant patient morbidity if compromised. The aim of this study is to
      propose and validate a method to exploit functional information for the
      identification of fOARs in CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery
      treatment planning; in particular, given the high spatial accuracy offered by the
      CyberKnife system, local nonrigid registration is used to reach accurate image
      matching. Five patients affected by arteriovenous malformations (AVMs) and
      scheduled to undergo radiosurgery were scanned prior to treatment using computed
      tomography (CT), three-dimensional (3D) rotational angiography (3DRA), T2
      weighted and blood oxygenation level dependent echo planar imaging MRI. Tasks
      were chosen on the basis of lesion location by considering those areas which
      could be potentially close to treatment targets. Functional data were
      superimposed on 3DRA and CT used for treatment planning. The procedure for the
      localization of fMRI areas was validated by direct cortical stimulation on 38 AVM
      and tumor patients undergoing conventional surgery. Treatment plans studied with
      and without considering fOARs were significantly different, in particular with
      respect to both maximum dose and dose volume histograms; consideration of the
      fOARs allowed quality indices of treatment plans to remain almost constant or to
      improve in four out of five cases compared to plans with no consideration of
      fOARs. In conclusion, the presented method provides an accurate tool for the
      integration of functional information into AVM radiosurgery, which might help to
      minimize undesirable side effects and to make radiosurgery less invasive.

PMID- 17500449
TI  - Influence of monitor chamber calibration on virtual Wedge dosimetry.
AB  - We have investigated the influence of the linear accelerator (LINAC) monitor
      chamber calibration on the dosimetry of Siemens Virtual Wedge (VW.) The doses
      delivered in the three phases of wedge delivery (initial gap, sweep portion, and
      open field) utilize the ionization current generated in two dose monitoring ion
      chambers (MONITOR 1 and MONITOR 2) in the LINAC to control the wedge delivery. We
      intentionally offset the calibration of each of these chambers by +/- 3% and
      observed up to a 13% change in the dose along the wedge profile for a 6 MV beam
      at a field size of 20 x 20 cm2. If the calibration of one of the two dose
      monitoring chambers changed independently then the relative dose at points along
      the wedge profile were affected. Furthermore, the percentage change in dose
      varied across the wedge profile thereby affecting the wedge angle as well as the
      central axis wedge factor. We also present equations for calculating the change
      in dose at a position along the wedge profile as a function of monitor chamber
      calibration. A comparison with measurement showed that our theoretical
      predictions were accurate to within +/- 1.7%. The equations have proven useful
      tools in evaluating periodic drifts in VW dosimetry.

PMID- 17500450
TI  - Evaluation of the accuracy of fetal dose estimates using TG-36 data.
AB  - The American Association of Physicists in Medicine Radiation Therapy Committee
      Task Group 36 report (TG-36) provides guidelines for managing radiation therapy
      of pregnant patients. Included in the report are data that can be used to
      estimate the dose to the fetus. The purpose of this study is to evaluate the
      accuracy of these fetal dose estimates as compared to clinically measured values.
      TG-36 calculations were performed and compared with measurements of the fetal
      dose made in vivo or in appropriately-designed phantoms. Calculation and
      measurement data was collected for eight pregnant patients who underwent
      radiation therapy at the MD Anderson Cancer Center as well as for several fetal
      dose studies in the literature. The maximum measured unshielded fetal dose was 47
      cGy, which was 1.5% of the prescription dose. For all cases, TG-36 calculations
      and measured fetal doses differed by up to a factor of 3--the ratio of the
      calculated to measured dose ranged from 0.34 to 2.93. On average, TG-36
      calculations underestimated the measured dose by 31%. No significant trends in
      the relationship between the calculated and measured fetal doses were found based
      on the distance from, or the size of, the treatment field.

PMID- 17500451
TI  - Development of an inverse optimization package to plan nonuniform dose
      distributions based on spatially inhomogeneous radiosensitivity extracted from
      biological images.
AB  - An inverse optimization package which is capable of generating nonuniform dose
      distribution with subregional dose escalation is developed to achieve maximum
      equivalent uniform dose (EUD) for target while keeping the critical structure
      doses as low as possible. Relative cerebral blood volume (rCBV) maps obtained
      with a dynamic susceptibility contrast-enhanced MRI technique were used to
      delineate spatial radiosensitivity distributions. The voxel rCBV was converted to
      voxel radiosensitivity parameters (e.g., alpha and alpha/beta) based on
      previously reported correlations between rCBV, tumor grade, and radiosensitivity.
      A software package, DOSEPAINT, developed using MATLAB, optimizes the beamlet
      weights to achieve maximum EUD for target while limiting doses to critical
      structures. Using DOSEPAINT, we have generated nonuniform 3D-dose distributions
      for selected patient cases. Depending on the variation of the pixel
      radiosensitivity, the subregional dose escalation can be as high as 35% of the
      uniform dose as planned conventionally. The target dose escalation comes from
      both the inhomogeneous radiosensitivities and the elimination of integral target
      dose constraint. The target EUDs are found to be higher than those for the
      uniform dose planned ignoring the spatial inhomogeneous radiosensitivity. The
      EUDs for organs at risk are found to be approximately equal to or lower than
      those for the uniform dose plans. In conclusion, we have developed a package that
      is capable of generating nonuniform dose distributions optimized for spatially
      inhomogeneous radiosensitivity. Subregional dose escalation may lead to increased
      treatment effectiveness as indicated by higher EUDs. The current development will
      impact biological image guided radiotherapy.

PMID- 17500452
TI  - On the discrepancies between Monte Carlo dose calculations and measurements for
      the 18 MV varian photon beam.
AB  - Significant discrepancies between Monte Carlo dose calculations and measurements
      for the Varian 18 MV photon beam with a large field size (40 x 40 cm2) were
      reported by different investigators. In this work, we investigated these
      discrepancies based on a new geometry model ("New Model") of the Varian 21EX
      linac using the GEPTS Monte Carlo code. Some geometric parameters used in
      previous investigations (Old Model) were inaccurate, as suggested by Chibani in
      his AAPM presentation (2004) and later confirmed by the manufacturer. The
      entrance and exit radii of the primary collimator of the New Model are 2 mm
      larger than previously thought. In addition to the corrected dimensions of the
      primary collimator, the New Model includes approximate models for the lead shield
      and the mirror frame between the monitor chamber and the Y jaws. A detailed
      analysis of the phase space data shows the effects of these corrections on the
      beam characteristics. The individual contributions from the linac component to
      the photon and electron fluences are calculated. The main source of discrepancy
      between measurements and calculations based on the Old Model is the
      underestimated electron contamination. The photon and electron fluences at the
      isocenter are 5.3% and 36% larger in the New Model in comparison with the Old
      Model. The flattening filter and the lead shield (plus the mirror frame)
      contribute 48.7% and 13% of the total electron contamination at the isocenter,
      respectively. For both open and filtered (2 mm Pb) fields, the calculated (New
      Model) and measured dose distributions are within 1% for depths larger than 1 cm.
      To solve the residual problem of large differences at shallow depths (8% at 0.25
      cm depth), the detailed geometry of an IC-10 ionization chamber was simulated and
      the dose in the air cavity was calculated for different positions on the central
      axis including at the surface, where half of the chamber is outside the phantom.
      The calculated and measured chamber responses are within 3% even at the zero
      depth.

PMID- 17500453
TI  - Rodent brain imaging with SPECT/CT.
AB  - We evaluated methods of imaging rat models of stroke in vivo using a single
      photon emission computed tomography (SPECT) system dedicated to small animal
      imaging (X-SPECT, Gamma Medica-Ideas, Northridge, CA). An animal model of
      ischemic stroke was developed for in vivo SPECT/CT imaging using the middle
      cerebral artery occlusion (MCAO) technique. The presence of cerebral ischemia was
      verified in ex vivo studies using triphenyltetrazolium chloride (TTC) staining.
      In vivo radionuclide imaging of cerebral blood flow was performed in rats
      following MCAO using dynamic planar imaging of 99mTc-exametazime with parallel
      hole collimation. This was followed immediately by in vivo radionuclide imaging
      of cerebral blood flow with 99mTc-exametazime in the same animals using 1-mm
      pinhole SPECT. Correlated computed tomography imaging was performed to localize
      radiopharmaceutical uptake. The animals were allowed to recover and ex vivo
      autoradiography was performed with separate administration of 99mTc-exametazime.
      Time activity curve of 99mTc-exametazime showed that the radiopharmaceutical
      uptake could be maintained for over 9 min. The activity would be expected to be
      relatively stable for a much longer period, although the data were only obtained
      for 9 min. TTC staining revealed sizable infarcts by visual observation of
      inexistence of TTC stain in infracted tissues of MCAO rat brains. In vivo SPECT
      imaging showed cerebral blood flow deficit in the MCAO model, and the in vivo
      imaging result was confirmed with ex vivo autoradiography. We have demonstrated a
      capability of imaging regions of cerebral blood flow deficit in MCAO rat brains
      in vivo using a pinhole SPECT dedicated to small animal imaging.

PMID- 17500454
TI  - Quantitative evaluation of free-form deformation registration for dynamic
      contrast-enhanced MR mammography.
AB  - In this paper, we present an evaluation study of a set of registration strategies
      for the alignment of sequences of 3D dynamic contrast-enhanced magnetic resonance
      breast images. The accuracy of the optimal registration strategies was determined
      on unseen data. The evaluation is based on the simulation of physically plausible
      breast deformations using finite element methods and on contrast-enhanced image
      pairs without visually detectable motion artifacts. The configuration of the
      finite element model was chosen according to its ability to predict in vivo
      breast deformations for two volunteers. We computed transformations for ten
      patients with 12 simulated deformations each. These deformations were applied to
      the postcontrast image to model patient motion occurring between pre- and
      postcontrast image acquisition. The original precontrast images were registered
      to the corresponding deformed postcontrast images. The performance of several
      registration configurations (rigid, affine, B-spline based nonrigid, single
      resolution, multi-resolution, and volume-preserving) was optimized for five of
      the ten patients. The images were most accurately aligned with volume-preserving
      single-resolution nonrigid registration employing 40 or 20 mm control point
      spacing. When tested on the remaining five patients the optimal configurations
      reduced the average mean registration error from 1.40 to 0.45 mm for the whole
      breast tissue and from 1.20 to 0.32 mm for the enhancing lesion. These results
      were obtained on average within 26 (81) min for 40 (20) mm control point spacing.
      The visual appearance of the difference images from 30 patients was significantly
      improved after 20 mm volume-preserving single-resolution nonrigid registration in
      comparison to no registration or rigid registration. No substantial volume
      changes within the region of the enhancing lesions were introduced by this
      nonrigid registration.

PMID- 17500455
TI  - Survey of computed tomography scanners in Taiwan: dose descriptors, dose guidance
      levels, and effective doses.
AB  - The IAEA and the ICRP recommended dose guidance levels for the most frequent
      computed tomography (CT) examinations to promote strategies for the optimization
      of radiation dose to CT patients. A national survey, including on-site
      measurements and questionnaires, was conducted in Taiwan in order to establish
      dose guidance levels and evaluate effective doses for CT. The beam quality and
      output and the phantom doses were measured for nine representative CT scanners.
      Questionnaire forms were completed by respondents from facilities of 146 CT
      scanners out of 285 total scanners. Information on patient, procedure, scanner,
      and technique for the head and body examinations was provided. The weighted
      computed tomography dose index (CTDI(w)), the dose length product (DLP), organ
      doses and effective dose were calculated using measured data, questionnaire
      information and Monte Carlo simulation results. A cost-effective analysis was
      applied to derive the dose guidance levels on CTDI(w) and DLP for several CT
      examinations. The mean effective dose +/- standard deviation distributes from 1.6
      +/- 0.9 mSv for the routine head examination to 13 +/- 11 mSv for the examination
      of liver, spleen, and pancreas. The surveyed results and the dose guidance levels
      were provided to the national authorities to develop quality control standards
      and protocols for CT examinations.

PMID- 17500456
TI  - Quantification of the impact of MLC modeling and tissue heterogeneities on
      dynamic IMRT dose calculations.
AB  - This study quantifies the dose prediction errors (DPEs) in dynamic IMRT dose
      calculations resulting from (a) use of an intensity matrix to estimate the multi
      leaf collimator (MLC) modulated photon fluence (DPE(IGfluence) instead of an
      explicit MLC particle transport, and (b) handling of tissue heterogeneities
      (DPE(hetero)) by superposition/convolution (SC) and pencil beam (PB) dose
      calculation algorithms. Monte Carlo (MC) computed doses are used as reference
      standards. Eighteen head-and-neck dynamic MLC IMRT treatment plans are
      investigated. DPEs are evaluated via comparing the dose received by 98% of the
      GTV (GTV D 98%), the CTV D 95%, the nodal D 90%, the cord and the brainstem D
      02%, the parotid D 50%, the parotid mean dose (D (Mean)), and generalized
      equivalent uniform doses (gEUDs) for the above structures. For the MC-generated
      intensity grids, DPE(IGfluence) is within +/- 2.1% for all targets and critical
      structures. The SC algorithm DPE(hetero) is within +/- 3% for 98.3% of the
      indices tallied, and within +/- 3.4% for all of the tallied indices. The PB
      algorithm DPE(hetero) is within +/- 3% for 92% of the tallied indices.
      Statistical equivalence tests indicate that PB DPE(hetero) requires a +/- 3.6%
      interval to state equivalence with the MC standard, while the intervals are <
      1.5% for SC DPE(hetero) and DPE(IGfluence). Overall, these results indicate that
      SC and MC IMRT dose calculations which use MC-derived intensity matrices for
      fluence prediction do not introduce significant dose errors compared with full
      Monte Carlo dose computations; however, PB algorithms may result in clinically
      significant dose deviations.

PMID- 17500457
TI  - Iterative threshold segmentation for PET target volume delineation.
AB  - The purpose of this work is to create a rigorous method of segmenting PET images
      using an automated iterative technique. To this end a phantom study employing
      spherical targets was used to determine local (slice specific) threshold levels
      which produce correct cross-sections based on the contrast between target and
      background. Numerous target to background activity concentration ratios were
      investigated but found to have minimal effect in comparison to the influence of
      target size. Functions were fit to this data and used to construct an iterative
      threshold segmentation algorithm. In all cases this approach yielded convergence
      within ten iterations. Iterative threshold segmentation was applied using both an
      axial and tri-axial approach to the spherical targets and also to two irregularly
      shaped volumes. Of these two approaches, the tri-axial method proved less
      susceptible to image noise and better at dealing with partial volume effects at
      the interface between target and background. For comparative purposes, single
      thresholds of 28% and 40% were also applied to the spherical data sets. The tri
      axial iterative method was found capable of delineating cross sections with areas
      greater than 250 mm2 to within the maximum resolution possible (1 pixel width).
      Cross sections of less than 250 mm2 in area were resolved by the tri-axial method
      to within 2 pixel widths of their true physical extent. Local contrast based
      iterative threshold segmentation shows promise as a method of rigorously
      delineating PET target volumes with good accuracy subject to the limitations
      imposed by the image resolution which currently characterizes this modality.

PMID- 17500458
TI  - Build-up and surface dose measurements on phantoms using micro-MOSFET in 6 and 10
      MV x-ray beams and comparisons with Monte Carlo calculations.
AB  - This work is intended to investigate the application and accuracy of micro-MOSFET
      for superficial dose measurement under clinically used MV x-ray beams. Dose
      response of micro-MOSFET in the build-up region and on surface under MV x-ray
      beams were measured and compared to Monte Carlo calculations. First, percentage
      depth-doses were measured with micro-MOSFET under 6 and 10 MV beams of normal
      incidence onto a flat solid water phantom. Micro-MOSFET data were compared with
      the measurements from a parallel plate ionization chamber and Monte Carlo dose
      calculation in the build-up region. Then, percentage-depth-doses were measured
      for oblique beams at 0 degrees-80 degrees onto the flat solid water phantom with
      micro-MOSFET placed at depths of 2 cm, 1 cm, and 2 mm below the surface.
      Measurements were compared to Monte Carlo calculations under these settings.
      Finally, measurements were performed with micro-MOSFET embedded in the first 1 mm
      layer of bolus placed on a flat phantom and a curved phantom of semi-cylindrical
      shape. Results were compared to superficial dose calculated from Monte Carlo for
      a 2 mm thin layer that extends from the surface to a depth of 2 mm. Results were
      (1) Comparison of measurements with MC calculation in the build-up region showed
      that micro-MOSFET has a water-equivalence thickness (WET) of 0.87 mm for 6 MV
      beam and 0.99 mm for 10 MV beam from the flat side, and a WET of 0.72 mm for 6 MV
      beam and 0.76 mm for 10 MV beam from the epoxy side. (2) For normal beam
      incidences, percentage depth dose agree within 3%-5% among micro-MOSFET
      measurements, parallel-plate ionization chamber measurements, and MC
      calculations. (3) For oblique incidence on the flat phantom with micro-MOSFET
      placed at depths of 2 cm, 1 cm, and 2 mm, measurements were consistent with MC
      calculations within a typical uncertainty of 3%-5%. (4) For oblique incidence on
      the flat phantom and a curved-surface phantom, measurements with micro-MOSFET
      placed at 1.0 mm agrees with the MC calculation within 6%, including
      uncertainties of micro-MOSFET measurements of 2%-3% (1 standard deviation),
      MOSFET angular dependence of 3.0%-3.5%, and 1%-2% systematical error due to
      phantom setup geometry asymmetry. Micro-MOSFET can be used for skin dose
      measurements in 6 and 10 MV beams with an estimated accuracy of +/- 6%.

PMID- 17500459
TI  - Monte Carlo aided design of an improved well-type ionization chamber for low
      energy brachytherapy sources.
AB  - The determination of the air kerma strength of a brachytherapy seed is necessary
      for effective treatment planning. Well-type ionization chambers are used on site
      at therapy clinics to determine the air kerma strength of seeds. In this work, an
      improved well-type ionization chamber for low energy, low dose rate brachytherapy
      sources is designed using Monte Carlo transport calculations to aid in the design
      process. The design improvements are the elimination of the air density induced
      over-response effect seen in other air-communicating chambers for low energy
      photon sources, and a larger signal strength (response or current) for 103Pd and
      125I based seeds. A prototype well chamber based on the Monte Carlo aided design
      but using graphite coated acrylic walls rather than the design basis air
      equivalent plastic (C-552) walls was constructed and experimentally evaluated.
      The prototype chamber produced an 85% stronger signal when measuring a commonly
      used 103Pd seed and a 26% stronger signal when measuring a commonly used 125I
      seed when compared to another commonly used well chamber. The normalized PTP
      corrected chamber response is, at most, 1.3% and 2.4% over unity for air
      densities/pressures corresponding to an elevation of 3048 m (10000 feet) above
      sea level for the commonly used 103Pd and 125I based seeds respectively.
      Comparing calculated and measured chamber responses for common 103Pd and 125I
      based brachytherapy seeds show agreement within 0.6% and 0.2%, respectively. We
      conclude that Monte Carlo transport calculations accurately model the response of
      this new well chamber and in general can be used to predict the response of well
      chambers. The prototype chamber built in this work responds as predicted by the
      Monte Carlo calculations.

PMID- 17500460
TI  - Introducing gel dosimetry in a clinical environment: customization of polymer gel
      composition and magnetic resonance imaging parameters used for 3D dose
      verifications in radiosurgery and intensity modulated radiotherapy.
AB  - Radiation sensitive gels have been used as dosimeters for clinical dose
      verification of different radiation therapy modalities. However, the use of gels
      is not widespread, because careful techniques are required to achieve the dose
      precision and accuracy aimed for in clinical dose verification. Here, the
      introduction of gel dosimetry in a clinical environment is described, including
      the whole chain of customizations and preparations required to introduce magnetic
      resonance (MR) based gel dosimetry into clinical routine. In order to standardize
      gel dosimetry in dose verifications for radiosurgery and intensity modulated
      radiotherapy (IMRT), we focused on both the customization of the gel composition
      and of the MR imaging parameters to increase its precision. The relative amount
      of the components of the normoxic, methacrylic acid based gel (MAGIC) was changed
      to obtain linear and steep dose response relationships. MR imaging parameters
      were customized for the different dose ranges used in order to lower the relative
      standard deviation of the measured transversal relaxation rate (R2). An
      optimization parameter was introduced to quantify the change in the relative
      standard deviation of R2 (sigma(R2,rel)) taking the increase in MR time into
      account. A 9% methacrylic acid gel customized for radiosurgery was found to give
      a linear dose response up to 40 Gy with a slope of 0.94 Gy(-1) s(-1), while a 6%
      methacrylic acid gel customized for IMRT had a linear range up to 3 Gy with a
      slope of 1.86 Gy(-1) s(-1). With the help of an introduced optimization
      parameter, the mean sigma(R2,rel) was improved by 13% for high doses and by 55%
      for low doses, without increasing MR time to unacceptable values. A mean dose
      resolution of less than 0.13 Gy has been achieved with the gel and imaging
      parameters customized for IMRT and a dose resolution from 0.97 Gy (at 5 Gy) to
      2.15 Gy (at 40 Gy) for the radiosurgery dose range. The comparisons of calculated
      and measured relative 3D dose distributions performed for radiosurgery and IMRT
      showed an acceptable overall correlation. The gamma criterion for the
      radiosurgery verification with a voxel size of 1.5 x 1.5 x 1.5 mm3 was passed by
      96.8% of the voxels (1.5 mm distance, 8% in dose). For the IMRT verification
      using a voxel size of 1.25 x 1.25 x 5 mm3 the gamma criterion was passed by 50.3%
      of the voxels (3 mm distance, 3% dose uncertainty). Using dedicated data analysis
      and visualization software, MR based normoxic gel dosimetry was found to be a
      valuable tool for clinically based dose verification, provided that customized
      gel compositions and MR imaging parameters are used. While high dose precision
      was achieved, further work is required to achieve clinically acceptable dose
      accuracy.

PMID- 17500461
TI  - Monte Carlo simulation of time-dependent, transport-limited fluorescent boundary
      measurements in frequency domain.
AB  - Recently, we have presented and experimentally validated a unique numerical
      solver of the coupled radiative transfer equations (RTEs) for rapidly computing
      time-dependent excitation and fluorescent light propagation in small animal
      tomography. Herein, we present a time-dependent Monte Carlo algorithm to validate
      the forward RTE solver and investigate the impact of physical parameters upon
      transport-limited measurements in order to best direct the development of the RTE
      solver for optical tomography. Experimentally, the Monte Carlo simulations for
      both transport-limited and diffusion-limited propagations are validated using
      frequency domain photon migration measurements for 1.0%, 0.5%, and 0.2%
      intralipid solutions containing 1 microM indocyanine green in a 49 cm3
      cylindrical phantom corresponding to the small volume employed in small animal
      tomography. The comparisons between Monte Carlo simulations and the numerical
      solutions result in mean percent error in amplitude and the phase shift less than
      5.0% and 0.7 degrees, respectively, at excitation and emission wavelengths for
      varying anisotropic factors, lifetimes, and modulation frequencies. Monte Carlo
      simulations indicate that the accuracy of the forward model is enhanced using (i)
      suitable source models of photon delivery, (ii) accurate anisotropic factors, and
      (iii) accurate acceptance angles of collected photons. Monte Carlo simulations
      also show that the accuracy of the diffusion approximation in the small phantom
      depends upon (i) the ratio d(phantom)/l(tr), where d(phantom) is the phantom
      diameter and l(tr) is the transport mean free path; and (ii) the anisotropic
      factor of the medium. The Monte Carlo simulations validates and guides the future
      development of an appropriate RTE solver for deployment in small animal optical
      tomography.

PMID- 17500462
TI  - Effects of pulsatile blood flow in large vessels on thermal dose distribution
      during thermal therapy.
AB  - The aim of this study is to evaluate the effect of pulsatile blood flow in
      thermally significant blood vessels on the thermal lesion region during thermal
      therapy of tumor. A sinusoidally pulsatile velocity profile for blood flow was
      employed to simulate the cyclic effect of the heart beat on the blood flow. The
      evolution of temperature field was governed by the energy transport equation for
      blood flow together with Pennes' bioheat equation for perfused tissue encircling
      the blood vessel. The governing equations were numerically solved by a novel
      multi-block Chebyshev pseudospectral method and the accumulated thermal dose in
      tissue was computed. Numerical results show that pulsatile velocity profile, with
      various combinations of pulsatile amplitude and frequency, has little difference
      in effect on the thermal lesion region of tissue compared with uniform or
      parabolic velocity profile. However, some minor differences on the thermal lesion
      region of blood vessel is observed for middle-sized blood vessel. This
      consequence suggests that, in this kind of problem, we may as well do the
      simulation simply by a steady uniform velocity profile for blood flow.

PMID- 17500463
TI  - Application of adjoint Monte Carlo to accelerate simulations of mono-directional
      beams in treatment planning for boron neutron capture therapy.
AB  - This paper deals with the application of the adjoint transport theory in order to
      optimize Monte Carlo based radiotherapy treatment planning. The technique is
      applied to Boron Neutron Capture Therapy where most often mixed beams of neutrons
      and gammas are involved. In normal forward Monte Carlo simulations the particles
      start at a source and lose energy as they travel towards the region of interest,
      i.e., the designated point of detection. Conversely, with adjoint Monte Carlo
      simulations, the so-called adjoint particles start at the region of interest and
      gain energy as they travel towards the source where they are detected. In this
      respect, the particles travel backwards and the real source and real detector
      become the adjoint detector and adjoint source, respectively. At the adjoint
      detector, an adjoint function is obtained with which numerically the same result,
      e.g., dose or flux in the tumor, can be derived as with forward Monte Carlo. In
      many cases, the adjoint method is more efficient and by that is much quicker
      when, for example, the response in the tumor or organ at risk for many locations
      and orientations of the treatment beam around the patient is required. However, a
      problem occurs when the treatment beam is mono-directional as the probability of
      detecting adjoint Monte Carlo particles traversing the beam exit (detector plane
      in adjoint mode) in the negative direction of the incident beam is zero. This
      problem is addressed here and solved first with the use of next event estimators
      and second with the application of a Legendre expansion technique of the angular
      adjoint function. In the first approach, adjoint particles are tracked
      deterministically through a tube to a (adjoint) point detector far away from the
      geometric model. The adjoint particles will traverse the disk shaped entrance of
      this tube (the beam exit in the actual geometry) perpendicularly. This method is
      slow whenever many events are involved that are not contributing to the point
      detector, e.g., neutrons in a scattering medium. In the second approach, adjoint
      particles that traverse an adjoint shaped detector plane are used to estimate the
      Legendre coefficients for expansion of the angular adjoint function. This
      provides an estimate of the adjoint function for the direction normal to the
      detector plane. In a realistic head model, as described in this paper, which is
      surrounded by 1020 mono-directional neutron/gamma beams and from which the best
      ones are to be selected, the example calculates the neutron and gamma fluxes in
      ten tumors and ten organs at risk. For small diameter beams (5 cm), and with
      comparable relative errors, forward Monte Carlo is seen to be 1.5 times faster
      than the adjoint Monte Carlo techniques. For larger diameter neutron beams (10
      and 15 cm), the Legendre technique is found to be 6 and 20 times faster,
      respectively. In the case of gammas alone, for the 10 and 15 cm diam beams, both
      adjoint Monte Carlo Legendre and point detector techniques are respectively 2 and
      3 times faster than forward Monte Carlo.

PMID- 17500464
TI  - Pulmonary nodule registration in serial CT scans based on rib anatomy and nodule
      template matching.
AB  - An automated method is being developed in order to identify corresponding nodules
      in serial thoracic CT scans for interval change analysis. The method uses the rib
      centerlines as the reference for initial nodule registration. A spatially
      adaptive rib segmentation method first locates the regions where the ribs join
      the spine, which define the starting locations for rib tracking. Each rib is
      tracked and locally segmented by expectation-maximization. The ribs are
      automatically labeled, and the centerlines are estimated using skeletonization.
      For a given nodule in the source scan, the closest three ribs are identified. A
      three-dimensional (3D) rigid affine transformation guided by simplex optimization
      aligns the centerlines of each of the three rib pairs in the source and target CT
      volumes. Automatically defined control points along the centerlines of the three
      ribs in the source scan and the registered ribs in the target scan are used to
      guide an initial registration using a second 3D rigid affine transformation. A
      search volume of interest (VOI) is then located in the target scan. Nodule
      candidate locations within the search VOI are identified as regions with high
      Hessian responses. The initial registration is refined by searching for the
      maximum cross-correlation between the nodule template from the source scan and
      the candidate locations. The method was evaluated on 48 CT scans from 20
      patients. Experienced radiologists identified 101 pairs of corresponding nodules.
      Three metrics were used for performance evaluation. The first metric was the
      Euclidean distance between the nodule centers identified by the radiologist and
      the computer registration, the second metric was a volume overlap measure between
      the nodule VOIs identified by the radiologist and the computer registration, and
      the third metric was the hit rate, which measures the fraction of nodules whose
      centroid computed by the computer registration in the target scan falls within
      the VOI identified by the radiologist. The average Euclidean distance error was
      2.7 +/- 3.3 mm. Only two pairs had an error larger than 10 mm. The average volume
      overlap measure was 0.71 +/- 0.24. Eighty-three of the 101 pairs had ratios
      larger than 0.5, and only two pairs had no overlap. The final hit rate was
      93/101.

PMID- 17500465
TI  - Quality assurance of HDR 192Ir sources using a Fricke dosimeter.
AB  - A prototype of a Fricke dosimetry system consisting of a 15 x 15 x 15 cm3 water
      phantom made of Plexiglas and a 11.3-ml Pyrex balloon fitted with a 0.2 cm thick
      Pyrex sleeve in its center was created to assess source strength and treatment
      planning algorithms for use in high dose rate (HDR) 192Ir afterloading units. In
      routine operation, the radioactive source is positioned at the end of a sleeve,
      which coincides with the center of the spherical balloon that is filled with
      Fricke solution, so that the solution is nearly isotropically irradiated. The
      Fricke system was calibrated in terms of source strength against a reference well
      type ionization chamber, and in terms of radial dose by means of an existing
      algorithm from the HDR's treatment planning system. Because the system is based
      on the Fricke dosimeter itself, for a given type and model of 192Ir source, the
      system needs initial calibration but no recalibration. The results from
      measurements made over a 10 month period, including source decay and source
      substitutions, have shown the feasibility of using such a system for quality
      control (QC) of HDR afterloading equipment, including both the source activity
      and treatment planning parameters. The benefit of a large scale production and
      the use of this device for clinical HDR QC audits via mail are also discussed.

PMID- 17500466
TI  - Three-dimensional heart dose reconstruction to estimate normal tissue
      complication probability after breast irradiation using portal dosimetry.
AB  - Irradiation of the heart is one of the major concerns during radiotherapy of
      breast cancer. Three-dimensional (3D) treatment planning would therefore be
      useful but cannot always be performed for left-sided breast treatments, because
      CT data may not be available. However, even if 3D dose calculations are available
      and an estimate of the normal tissue damage can be made, uncertainties in patient
      positioning may significantly influence the heart dose during treatment.
      Therefore, 3D reconstruction of the actual heart dose during breast cancer
      treatment using electronic imaging portal device (EPID) dosimetry has been
      investigated. A previously described method to reconstruct the dose in the
      patient from treatment portal images at the radiological midsurface was used in
      combination with a simple geometrical model of the irradiated heart volume to
      enable calculation of dose-volume histograms (DVHs), to independently verify this
      aspect of the treatment without using 3D data from a planning CT scan. To
      investigate the accuracy of our method, the DVHs obtained with full 3D treatment
      planning system (TPS) calculations and those obtained after resampling the TPS
      dose in the radiological midsurface were compared for fifteen breast cancer
      patients for whom CT data were available. In addition, EPID dosimetry as well as
      3D dose calculations using our TPS, film dosimetry, and ionization chamber
      measurements were performed in an anthropomorphic phantom. It was found that the
      dose reconstructed using EPID dosimetry and the dose calculated with the TPS
      agreed within 1.5% in the lung/heart region. The dose-volume histograms obtained
      with EPID dosimetry were used to estimate the normal tissue complication
      probability (NTCP) for late excess cardiac mortality. Although the accuracy of
      these NTCP calculations might be limited due to the uncertainty in the NTCP
      model, in combination with our portal dosimetry approach it allows incorporation
      of the actual heart dose. For the anthropomorphic phantom, and for fifteen
      patients for whom CT data were available to test our method, the average
      difference between the NTCP values obtained with our method and those resulting
      from the dose distributions calculated with the TPS was 0.1% +/- 0.3% (1 SD).
      Most NTCP values were 1%-2% lower than those obtained using the method described
      by Hurkmans et al. [Radiother. Oncol. 62, 163-171 (2002)], using the maximum
      heart distance determined from a simulator image as a single pre-treatment
      parameter. A similar difference between the two methods was found for twelve
      patients using in vivo EPID dosimetry; the average NTCP value obtained with EPID
      dosimetry was 0.9%, whereas an average NTCP value of 2.2% was derived using the
      method of Hurkmans et al. The results obtained in this study show that EPID
      dosimetry is well suited for in vivo verification of the heart dose during breast
      cancer treatment, and can be used to estimate the NTCP for late excess cardiac
      mortality. To the best of our knowledge, this is the first study using portal
      dosimetry to calculate a DVH and NTCP of an organ at risk.

PMID- 17500467
TI  - The trouble with CTD100.
AB  - The computed tomography dose index (CTDI100) is typically measured using a 100 mm
      long pencil ion chamber with cylindrical polymethyl methacrylate (PMMA) dosimetry
      phantoms. While this metric was useful in the era of single slice CT scanners
      with collimated slice thicknesses of 10 mm or less, the efficiency of this metric
      in multi-slice CT scanners with wide (40 mm) collimated x-ray beams is unknown.
      Monte Carlo simulations were used to assess the efficiency of the CTDI100
      parameter for wider beam collimations. The simulations utilized the geometry of a
      commercially available CT scanner, with modeled polyenergetic x-ray spectra. Dose
      spread functions (DSFs) were computed along the length of 12.4 mm diam rods
      placed at several radii in infinitely long 160 mm diam (head) and 320 mm diam
      (body) PMMA phantoms. The DSFs were used to compute radiation dose profiles for
      slice thicknesses from 1 to 400 mm. CTDI00 efficiency was defined as the fraction
      of the dose along a PMMA rod collected in a 100 mm length centered on the CT
      slice position, divided by the total dose deposited along an infinitely long PMMA
      rod. For a 10 mm slice thickness, a 120 kVp x-ray spectrum, and the PMMA head
      phantom, the efficiency of the CTDI00 was 82% and 90% for the center and
      peripheral holes, respectively. The corresponding efficiency values for the body
      phantom were 63% and 88%. These values are reduced by only 1% when a 40 mm slice
      thickness was studied, so the use of CTDI00 for 40 mm wide x-ray beams is no less
      valid than its use for 10 mm beam widths. However, these data illustrate that the
      efficiency of the CTDI100 measurement even with 10 mm beam widths is low and,
      consequently, dose computations which are derived from this metric may not be as
      accurate as desirable.

PMID- 17500468
TI  - An intercomparison between film dosimetry and diode matrix for IMRT quality
      assurance.
AB  - The evaluation of the agreement between measured and calculated dose plays an
      essential role in the quality assurance (QA) procedures for intensity modulated
      radiation therapy (IMRT). Film dosimetry has been widely adopted for this purpose
      due to excellent film characteristics in terms of spatial resolution;
      unfortunately, it is a time-consuming procedure and requires great care if film
      has to be used as an absolute dosimeter. If this is not the case, then an
      independent ionimetric measurement is mandatory to assess the absolute dose
      agreement. Arrays of detectors are now replacing films for routine IMRT QA, since
      they permit very simple verification procedures. They show excellent
      characteristics in terms of linearity, repeatability, and independence of the
      response from the dose rate, but at the same time present a poor spatial
      resolution, due to the limited number of detectors available. In our institution,
      a diode matrix (MapCHECK, provided by Sun Nuclear) is adopted for routine QA. The
      aim of this work is to compare the performances of absolute film dosimetry with
      this matrix in QA procedures and to investigate the origin of possible
      discrepancies between the two methods. The results we present show a very good
      agreement between the two detectors when used to assess the mean dose deviation
      between calculated and measured doses (in both cases 0.2%). If the y matrix
      method is adopted, MapCHECK response shows a slightly better agreement with
      computed dose distribution than film dosimetry (mean percentage of points
      satisfying the constraint y < or = 1: 96% versus 94%). This difference is shown
      not to depend on the different field sampling, but on the detectors'
      capabilities. Moreover, we show that the diode matrix is able to identify
      eventual delivery errors as well as film. Our conclusion is that the diode matrix
      may effectively replace both film dosimetry and ionimetric measurements in
      routine IMRT QA.

PMID- 17500469
TI  - Intraoperative cone-beam CT for correction of periaxial malrotation of the
      femoral shaft: a surface-matching approach.
AB  - Limb length, alignment and rotation can be difficult to determine in femoral
      shaft fractures. Shaft axis rotation is particularly difficult to assess
      intraoperatively. Femoral malpositioning can cause deformity, pain and secondary
      degenerative joint damage. The aim of this study is to develop an intraoperative
      method based on cone-beam computed tomography (CBCT) to guide alignment of
      femoral shaft fractures. We hypothesize that bone surface matching can predict
      malrotation even with severe comminution. A cadaveric femur was imaged at 16
      femoral periaxial malrotations (-51.2 degrees to 60.1 degrees). The images were
      processed resulting in an unwrapped bone surface plot consisting of a pattern of
      ridges and valleys. Fracture gaps were simulated by removing midline CT slices.
      The gaps were reconstituted by extrapolating the existing proximal and distal
      fragments to the midline of the fracture. The two bone surfaces were then shifted
      to align bony features. Periaxial malrotation was accurately assessed using
      surface matching (r2 = 0.99, slope 1.0). The largest mean error was 2.20 degrees
      and the average difference between repeated measurements was 0.49 degrees. CBCT
      can provide intraoperative high-resolution images with a large field of view.
      This quality of imaging enables surface matching algorithms to be utilized even
      with large areas of comminution.

PMID- 17500470
TI  - Variations in energy spectra and water-to-material stopping-power ratios in three
      dimensional conformal and intensity-modulated photon fields.
AB  - Because of complex dose distributions and dose gradients that are created in
      three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated
      radiation therapy (IMRT), photon- and electron-energy spectra might change
      significantly with spatial locations and doses. This study examined variations in
      photon- and electron-energy spectra in 3D-CRT and IMRT photon fields. The effects
      of spectral variations on water-to-material stopping-power ratios used in Monte
      Carlo treatment planning systems and the responses of energy-dependent
      dosimeters, such as thermoluminescent dosimeters (TLDs) and radiographic films
      were further studied. The EGSnrc Monte Carlo code was used to simulate
      megavoltage 3D-CRT and IMRT photon fields. The photon- and electron-energy
      spectra were calculated in 3D water phantoms and anthropomorphic phantoms based
      on the fluence scored in voxel grids. We then obtained the water-to-material
      stopping-power ratios in the local voxels using the Spencer-Attix cavity theory.
      Changes in the responses of films and TLDs were estimated based on the calculated
      local energy spectra and published data on the dosimeter energy dependency.
      Results showed that the photon-energy spectra strongly depended on spatial
      positions and doses in both the 3D-CRT and IMRT fields. The relative fraction of
      low-energy photons (< 100 keV) increased inversely with the photon dose in low
      dose regions of the fields. A similar but smaller effect was observed for
      electrons in the phantoms. The maximum variation of the water-to-material
      stopping-power ratio over the range of calculated dose for both 3D-CRT and IMRT
      was negligible (< 1.0%) for ICRU tissue, cortical bone, and soft bone and less
      than 3.6% for dry air and lung. Because of spectral softening at low doses,
      radiographic films in the phantoms could over-respond to dose by more than 30%,
      whereas the over-response of TLDs was less than 10%. Thus, spatial variations of
      the photon- and electron-energy spectra should be considered as important factors
      in 3D-CRT and IMRT dosimetry.

PMID- 17500471
TI  - Monte Carlo simulation of x-ray buildup factors of lead and its applications in
      shielding of diagnostic x-ray facilities.
AB  - X-ray buildup factors of lead in broad beam geometry for energies from 15 to 150
      keV are determined using the general purpose Monte Carlo N-particle radiation
      transport computer code (MCNP4C). The obtained buildup factors data are fitted to
      a modified three parameter Archer et al. model for ease in calculating the broad
      beam transmission with computer at any tube potentials/ filters combinations in
      diagnostic energies range. An example for their use to compute the broad beam
      transmission at 70, 100, 120, and 140 kVp is given. The calculated broad beam
      transmission is compared to data derived from literature, presenting good
      agreement. Therefore, the combination of the buildup factors data as determined
      and a mathematical model to generate x-ray spectra provide a computationally
      based solution to broad beam transmission for lead barriers in shielding x-ray
      facilities.

PMID- 17500472
TI  - Inversion with early photons.
AB  - Optical tomography using early photons can improve resolution and reduce the ill
      posed nature of the inversion problem. In this work we use 360 degrees projection
      experimental data to investigate the inversion performance of three commonly used
      numerical inversion methods: the random algebraic reconstruction technique
      (rART), singular value decomposition (SVD), and the conjugate-gradient-type
      method LSQR. Results are contrasted to each other and the effects of different
      photon propagation models are also investigated. We find that all methods perform
      adequately given appropriate regularization parameters, and that an
      experimentally measured photon weight function yields superior results over two
      approximate weights that have been previously used.

PMID- 17500473
TI  - Photon spectrometry for the determination of the dose-rate constant of low-energy
      photon-emitting brachytherapy sources.
AB  - Accurate determination of dose-rate constant (lambda) for interstitial
      brachytherapy sources emitting low-energy photons (< 50 keV) has remained a
      challenge in radiation dosimetry because of the lack of a suitable absolute
      dosimeter for accurate measurement of the dose rates near these sources. Indeed,
      a consensus value of lambda taken as the arithmetic mean of the dose-rate
      constants determined by different research groups and dosimetry techniques has to
      be used at present for each source model in order to minimize the uncertainties
      associated with individual determinations of lambda. Because the dosimetric
      properties of a source are fundamentally determined by the characteristics of the
      photons emitted by the source, a new technique based on photon spectrometry was
      developed in this work for the determination of dose-rate constant. The photon
      spectrometry technique utilized a high-resolution gamma-ray spectrometer to
      measure source-specific photon characteristics emitted by the low-energy sources
      and determine their dose-rate constants based on the measured photon-energy
      spectra and known dose-deposition properties of mono-energetic photons in water.
      This technique eliminates many of the difficulties arising from detector size,
      the energy dependence of detector sensitivity, and the use of non-water
      equivalent solid phantoms in absolute dose rate measurements. It also circumvents
      the uncertainties that might be associated with the source modeling in Monte
      Carlo simulation techniques. It was shown that the estimated overall uncertainty
      of the photon spectrometry technique was less than 4%, which is significantly
      smaller than the reported 8-10% uncertainty associated with the current thermo
      luminescent dosimetry technique. In addition, the photon spectrometry technique
      was found to be stable and quick in lambda determination after initial setup and
      calibration. A dose-rate constant can be determined in less than two hours for
      each source. These features make it ideal to determine the dose-rate constant of
      each source model from a larger and more representative sample of actual sources
      and to use it as a quality assurance resource for periodic monitoring of the
      constancy of lambda for brachytherapy sources used in patient treatments.

PMID- 17500474
TI  - Maximizing the potential of direct aperture optimization through collimator
      rotation.
AB  - Intensity-modulated radiation therapy (IMRT) treatment plans are conventionally
      produced by the optimization of fluence maps followed by a leaf sequencing step.
      An alternative to fluence based inverse planning is to optimize directly the leaf
      positions and field weights of multileaf collimator (MLC) apertures. This
      approach is typically referred to as direct aperture optimization (DAO). It has
      been shown that equivalent dose distributions may be generated that have
      substantially fewer monitor units (MU) and number of apertures compared to
      fluence based optimization techniques. Here we introduce a DAO technique with
      rotated apertures that we call rotating aperture optimization (RAO). The
      advantages of collimator rotation in IMRT have been shown previously and include
      higher fluence spatial resolution, increased flexibility in the generation of
      aperture shapes and less interleaf effects. We have tested our RAO algorithm on a
      complex C-shaped target, seven nasopharynx cancer recurrences, and one
      multitarget nasopharynx carcinoma patient. A study was performed in order to
      assess the capabilities of RAO as compared to fixed collimator angle DAO. The
      accuracy of fixed and rotated collimator aperture delivery was also verified. An
      analysis of the optimized treatment plans indicates that plans generated with RAO
      are as good as or better than DAO while maintaining a smaller number of apertures
      and MU than fluence based IMRT. Delivery verification results show that RAO is
      less sensitive to tongue and groove effects than DAO. Delivery time is currently
      increased due to the collimator rotation speed although this is a mechanical
      limitation that can be eliminated in the future.

PMID- 17500475
TI  - Effects of Hounsfield number conversion on CT based proton Monte Carlo dose
      calculations.
AB  - The Monte Carlo method provides the most accurate dose calculations on a patient
      computed tomography (CT) geometry. The increase in accuracy is, at least in part,
      due to the fact that instead of treating human tissues as water of various
      densities as in analytical algorithms, the Monte Carlo method allows human
      tissues to be characterized by elemental composition and mass density, and hence
      allows the accurate consideration of all relevant electromagnetic and nuclear
      interactions. On the other hand, the algorithm to convert CT Hounsfield numbers
      to tissue materials for Monte Carlo dose calculation introduces uncertainties.
      There is not a simple one to one correspondence between Hounsfield numbers and
      tissue materials. To investigate the effects of Hounsfield number conversion for
      proton Monte Carlo dose calculations, clinical proton treatment plans were
      simulated using the Geant4 Monte Carlo code. Three Hounsfield number to material
      conversion methods were studied. The results were compared in forms of dose
      volume histograms of gross tumor volume and clinical target volume. The
      differences found are generally small but can be dosimetrically significant.
      Further, different methods may cause deviations in the predicted proton beam
      range in particular for deep proton fields. Typically, slight discrepancies in
      mass density assignments play only a minor role in the target region, whereas
      more significant effects are caused by different assignments in elemental
      compositions. In the presence of large tissue inhomogeneities, for head and neck
      treatments, treatment planning decisions could be affected by these differences
      because of deviations in the predicted tumor coverage. Outside the target area,
      differences in elemental composition and mass density assignments both may play a
      role. This can lead to pronounced effects for organs at risk, in particular in
      the spread-out Bragg peak penumbra or distal regions. In addition, the
      significance of the elemental composition effect (dose to water vs. dose to
      tissue) is tissue-type dependent and is also affected by nuclear reactions.

PMID- 17500476
TI  - Detection of coronary calcifications from computed tomography scans for automated
      risk assessment of coronary artery disease.
AB  - A fully automated method for coronary calcification detection from non-contrast
      enhanced, ECG-gated multi-slice computed tomography (CT) data is presented.
      Candidates for coronary calcifications are extracted by thresholding and
      component labeling. These candidates include coronary calcifications,
      calcifications in the aorta and in the heart, and other high-density structures
      such as noise and bone. A dedicated set of 64 features is calculated for each
      candidate object. They characterize the object's spatial position relative to the
      heart and the aorta, for which an automatic segmentation scheme was developed,
      its size and shape, and its appearance, which is described by a set of
      approximated Gaussian derivatives for which an efficient computational scheme is
      presented. Three classification strategies were designed. The first one tested
      direct classification without feature selection. The second approach also
      utilized direct classification, but with feature selection. Finally, the third
      scheme employed two-stage classification. In a computationally inexpensive first
      stage, the most easily recognizable false positives were discarded. The second
      stage discriminated between more difficult to separate coronary calcium and other
      candidates. Performance of linear, quadratic, nearest neighbor, and support
      vector machine classifiers was compared. The method was tested on 76 scans
      containing 275 calcifications in the coronary arteries and 335 calcifications in
      the heart and aorta. The best performance was obtained employing a two-stage
      classification system with a k-nearest neighbor (k-NN) classifier and a feature
      selection scheme. The method detected 73.8% of coronary calcifications at the
      expense of on average 0.1 false positives per scan. A calcium score was computed
      for each scan and subjects were assigned one of four risk categories based on
      this score. The method assigned the correct risk category to 93.4% of all scans.

PMID- 17500477
TI  - The impact of breathing motion versus heterogeneity effects in lung cancer
      treatment planning.
AB  - The purpose of this study is to investigate the effects of tissue heterogeneity
      and breathing-induced motion/deformation on conformal treatment planning for
      pulmonary tumors and to compare the magnitude and the clinical importance of
      changes induced by these effects. Treatment planning scans were acquired at
      normal exhale/inhale breathing states for fifteen patients. The internal target
      volume (ITV) was defined as the union of exhale and inhale gross tumor volumes
      uniformly expanded by 5 mm. Anterior/posterior opposed beams (AP/PA) and three
      dimensional (3D)-conformal plans were designed using the unit-density exhale
      ("static") dataset. These plans were further used to calculate (a) density
      corrected ("heterogeneous") static dose and (b) heterogeneous cumulative dose,
      including breathing deformations. The DPM Monte Carlo code was used for dose
      computations. For larger than coin-sized tumors, relative to unit-density plans,
      tumor and lung doses increased in the heterogeneity-corrected plans. In comparing
      cumulative and static plans, larger normal tissue complication probability
      changes were observed for tumors with larger motion amplitudes and uncompensated
      breathing-induced hot/cold spots in lung. Accounting for tissue heterogeneity
      resulted in average increases of 9% and 7% in mean lung dose (MLD) for the 6 MV
      and 15 MV photon beams, respectively. Breathing-induced effects resulted in
      approximately 1% and 2% average decreases in MLD from the static value, for the 6
      and 15 MV photon beams, respectively. The magnitude of these effects was not
      found to correlate with the treatment plan technique, i.e., AP/PA versus 3D-CRT.
      Given a properly designed ITV, tissue heterogeneity effects are likely to have a
      larger clinical significance on tumor and normal lung treatment evaluation
      metrics than four-dimensional respiratory-induced changes.

PMID- 17500478
TI  - Hyperfast parallel-beam and cone-beam backprojection using the cell general
      purpose hardware.
AB  - Tomographic image reconstruction, such as the reconstruction of computed
      tomography projection values, of tomosynthesis data, positron emission tomography
      or SPECT events, and of magnetic resonance imaging data is computationally very
      demanding. One of the most time-consuming steps is the backprojection. Recently,
      a novel general purpose architecture optimized for distributed computing became
      available: the cell broadband engine (CBE). To maximize image reconstruction
      speed we modified our parallel-beam backprojection algorithm [two dimensional
      (2D)] and our perspective backprojection algorithm [three dimensional (3D), cone
      beam for flat-panel detectors] and optimized the code for the CBE. The algorithms
      are pixel or voxel driven, run with floating point accuracy and use linear (LI)
      or nearest neighbor (NN) interpolation between detector elements. For the
      parallel-beam case, 512 projections per half rotation, 1024 detector channels,
      and an image of size 512(2) was used. The cone-beam backprojection performance
      was assessed by backprojecting a full circle scan of 512 projections of size
      1024(2) into a volume of size 512(3) voxels. The field of view was chosen to
      completely lie within the field of measurement and the pixel or voxel size was
      set to correspond to the detector element size projected to the center of
      rotation divided by square root of 2. Both the PC and the CBE were clocked at 3
      GHz. For the parallel backprojection of 512 projections into a 512(2) image, a
      throughput of 11 fps (LI) and 15 fps (NN) was measured on the PC, whereas the CBE
      achieved 126 fps (LI) and 165 fps (NN), respectively. The cone-beam
      backprojection of 512 projections into the 512(3) volume took 3.2 min on the PC
      and is as fast as 13.6 s on the cell. Thereby, the cell greatly outperforms
      today's top-notch backprojections based on graphical processing units. Using both
      CBEs of our dual cell-based blade (Mercury Computer Systems) allows to 2D
      backproject 330 images/s and one can complete the 3D cone-beam backprojection in
      6.8 s.

PMID- 17500479
TI  - Accuracy and stability of positioning in radiosurgery: long-term results of the
      Gamma Knife system.
AB  - The primary aim of this investigation was to determine the long term overall
      accuracy of an irradiation position of Gamma Knife systems. The mechanical
      accuracy of the system as well as the overall accuracy of an irradiation position
      was examined by irradiating radiosensitive films. To measure the mechanical
      accuracy, the GafChromic film was fixed by a special tool at the unit center
      point (UCP). For overall accuracy the film was mounted inside a phantom at a
      target position given by a two-dimensional cross. Its position was determined by
      CT or MRI scans, a treatment was planned to hit this target by use of the
      standard planning software and the radiation was finally delivered. This
      procedure is named "system test" according to DIN 6875-1 and is equivalent to a
      treatment simulation. The used GafChromic films were evaluated by high resolution
      densitometric measurements. The Munich Gamma Knife UCP coincided within x; y; z: 
      0.014 +/- 0.09 mm; 0.013 +/- 0.09 mm; -0.002 +/- 0.06 mm (mean +/- SD) to the
      center of dose distribution. There was no trend in the measured data observed
      over more than ten years. All measured data were within a sphere of 0.2 mm
      radius. When basing the target definition in the system test on MRI scans, we
      obtained an overall accuracy of an irradiation position in the x direction of
      0.21 +/- 0.32 mm and in the y direction 0.15 +/- 0.26 mm (mean +/- SD). When a CT
      based target definition was used, we measured distances in x direction 0.06 +/-
      0.09 mm and in y direction 0.04 +/- 0.09 mm (mean +/- SD), respectively. These
      results were compared with those obtained with a Gamma Knife equipped with an
      automatic positioning system (APS) by use of a different phantom. This phantom
      was found to be slightly less accurate due to its mechanical construction and the
      soft fixation into the frame. The phantom related position deviation was found to
      be about +/- 0.2 mm, and therefore the measured accuracy of the APS Gamma Knife
      was evidently less precise by additional +/- 0.2 mm. These measurements
      demonstrate that an irradiation position defined by a CT scan can be hit within
      the intrinsic system precision. In radiosurgery with the Gamma Knife, a fixation
      with the Leksell stereotactic frame is applied. As this frame is considered to
      add no further uncertainties due to patient movements, the measured accuracy
      applies to a real patient treatment situation. The major contribution to the
      overall accuracy of an irradiation position is given by the MRI scans.

PMID- 17500480
TI  - Manual planimetric measurement of carotid plaque volume using three-dimensional
      ultrasound imaging.
AB  - We investigated the utility of three manual planimetric methods to quantify
      carotid plaque volume. A single observer measured 15 individual plaques from 15
      three-dimensional (3D) ultrasound (3D US) images of patients ten times each using
      three different planimetric approaches. Individual plaque volumes were measured
      (range: 32.6-597.1 mm3) using a standard planimetric approach (M1) whereby a
      plaque end was identified and sequential contours were measured. The same plaques
      were measured using a second approach (M2), whereby plaque ends were first
      identified and the 3D US image of the plaque was then subdivided into equal
      intervals. A third method (M3) was used to measure total plaque burden (range:
      165.1-1080.0 mm3) in a region (+/- 1.5 cm) relative to the carotid bifurcation.
      M1 systematically underestimated individual plaque volume compared to M2 (V2 = V1
      + 14.0 mm3, r = 0.99, p = 0.006) due to a difference in the mean plaque length
      measured. Coefficients of variance (CV) for M1 and M2 decrease with increasing
      plaque volume, with M2 results less than M1. Root mean square difference between
      experimental and theoretical CV for M2 was 3.2%. The standard deviation in the
      identification of the transverse location of the carotid bifurcation was 0.56 mm.
      CVs for plaque burden measured using M3 ranged from 1.2% to 7.6% and were less
      than CVs determined for individual plaque volumes of the same volume. The utility
      of M3 was demonstrated by measuring carotid plaque burden and volume change over
      a period of 3 months in three patients. In conclusion, M2 was determined to be a
      more superior measurement technique than M1 to measure individual plaque volume.
      Furthermore, we demonstrated the utility of M3 to quantify regional plaque burden
      and to quantify change in plaque volume.

PMID- 17500481
TI  - Quantifying lateral tissue heterogeneities in hadron therapy.
AB  - In radiotherapy with scanned particle beams, tissue heterogeneities lateral to
      the beam direction are problematic in two ways: they pose a challenge to dose
      calculation algorithms, and they lead to a high sensitivity to setup errors. In
      order to quantify and avoid these problems, a heterogeneity number H(i) as a
      method to quantify lateral tissue heterogeneities of single beam spot i is
      introduced. To evaluate this new concept, two kinds of potential errors were
      investigated for single beam spots: First, the dose calculation error has been
      obtained by comparing the dose distribution computed by a simple pencil beam
      algorithm to more accurate Monte Carlo simulations. The resulting error is
      clearly correlated with H(i). Second, the analysis of the sensitivity to setup
      errors of single beam spots also showed a dependence on H(i). From this data it
      is concluded that H(i) can be used as a criterion to assess the risks of a
      compromised delivered dose due to lateral tissue heterogeneities. Furthermore, a
      method how to incorporate this information into the inverse planning process for
      intensity modulated proton therapy is presented. By suppressing beam spots with a
      high value of H(i), the unfavorable impact of lateral tissue heterogeneities can
      be reduced, leading to treatment plans which are more robust to dose calculation
      errors of the pencil beam algorithm. Additional possibilities to use the
      information of H(i) are outlined in the discussion.

PMID- 17500482
TI  - In vitro study of cell survival following dynamic MLC intensity-modulated
      radiation therapy dose delivery.
AB  - The possibility of reduced cell kill following intensity-modulated radiation
      therapy (IMRT) compared to conventional radiation therapy has been debated in the
      literature. This potential reduction in cell kill relates to prolonged treatment
      times typical of IMRT dose delivery and consequently increased repair of
      sublethal lesions. While there is some theoretical support to this reduction in
      cell kill published in the literature, direct experimental evidence specific to
      IMRT dose delivery patterns is lacking. In this study we present cell survival
      data for three cell lines: Chinese hamster V79 fibroblasts, human cervical
      carcinoma, SiHa and colon adenocarcinoma, WiDr. Cell survival was obtained for
      2.1 Gy delivered as acute dose with parallel-opposed pair (POP), irradiation time
      75 s, which served as a reference; regular seven-field IMRT, irradiation time 5
      min; and IMRT with a break for multiple leaf collimator (MLC) re-initialization
      after three fields were delivered, irradiation time 10 min. An actual seven-field
      dynamic MLC IMRT plan for a head and neck patient was used. The IMRT plan was
      generated for a Varian EX or iX linear accelerator with 120 leaf Millenium MLC.
      Survival data were also collected for doses 1X, 2X, 3X, 4X, and 5x 2.1 Gy to
      establish parameters of the linear-quadratic equation describing survival
      following acute dose delivery. Cells were irradiated inside an acrylic
      cylindrical phantom specifically designed for this study. Doses from both IMRT
      and POP were validated using ion chamber measurements. A reproducible increase in
      cell survival was observed following IMRT dose delivery. This increase varied
      from small for V79, with a surviving fraction of 0.8326 following POP vs 0.8420
      following uninterrupted IMRT, to very pronounced for SiHa, with a surviving
      fraction of 0.3903 following POP vs 0.5330 for uninterrupted IMRT. When compared
      to IMRT or IMRT with a break for MLC initialization, cell survival following
      acute dose delivery was significantly different, p < 0.05, in three out of six
      cases. In contrast, when cell survival following IMRT was compared to that
      following IMRT with a break for MLC initialization the difference was always
      statistically insignificant. When projected to a 30 fraction treatment, dose
      deficit to bring cell survival to the same value as in POP was calculated as 4.1,
      24.9, and 31.1 Gy for V79, WiDr, and SiHa cell lines, respectively. The dose
      deficit did not relate to the alpha/beta ratio obtained in this study for the
      three cell lines. Clinical data do not show reduction in local control following
      IMRT. Possible reasons for this are discussed. The obtained data set can serve as
      a test data set for models designed to explore the effect of dose delivery
      prolongation/fractionation in IMRT on radiation therapy outcome.

PMID- 17500483
TI  - Crown restoration of the endodontically treated tooth: literature review.
AB  - The reviewed literature supports full crown restoration in all endodontically
      treated teeth other than incisors in humans [corrected] In general terms, a crown
      is a cemented, extra-coronal restoration that covers the entire outer surface of
      the clinical crown. Prosthodontic treatment, and particularly crown restoration
      in veterinary patients has been the subject of general informational articles and
      veterinary dental texts. These publications have discussed techniques for crown
      preparation, fabrication, and cementation as well as the general principles of
      prosthodontic treatment. The purpose of this review is to present available
      information on this topic in an organized manner which will help veterinary
      dentists to use an evidence-based approach when deciding on a type of final
      restoration for their endodontic patients.

PMID- 17500484
TI  - Validation of a new dental plaque quantification method in dogs.
AB  - Current methods for the quantification of plaque accumulation in cats and dogs
      are well-accepted adaptations of traditional human models, but have required
      substantial modifications in order to compensate for the inherent differences in
      compliance, cooperation, and temperament between animals and humans. While these
      modifications have sought to maintain or improve upon the accuracy and
      reproducibility of the original methods, they also have increased the complexity
      of the technique and have required additional scorer time and animal cooperation,
      which leads to increased cost of trials. Therefore, research was directed toward
      the development and validation of a new substrate scoring system that reduces
      resources while maintaining or increasing the reproducibility attributed to the
      more traditional methods. This new gingival contour plaque index was shown to be
      accurate and reproducible, but used fewer animals, required less time, and
      eliminated the need for many of the specialized procedures required by
      traditional methods.

PMID- 17500485
TI  - Orthodontic correction of a base narrow mandibular canine tooth in a cat.
AB  - A 6-month-old cat was diagnosed with a lingually displaced mandibular canine
      tooth causing palatal trauma. This case report describes the correction and
      outcome for orthodontic movement of the left mandibular canine tooth.

PMID- 17500487
TI  - Veterinary dental nomenclature.

PMID- 17500486
TI  - Osseous surgery to augment treatment of chronic periodontitis of canine teeth in
      a cat.

PMID- 17500488
TI  - Tooth preparation and impression for full metal crown restoration.

PMID- 17500489
TI  - Money matter$!

PMID- 17500490
TI  - Recent trends in the registered nurse labor market in the U.S.: short-run swings
      on top of long-term trends.
AB  - Drawing from labor economics, background information is provided for a deeper
      understanding of recent changes in the nurse labor market. The difference between
      the short and long-run supply of RNs are distinguished, and the economic forces
      that determine RNs' decision to be active in the labor market are explained. The
      ways the nurse labor market may change in the next few years are discussed.

PMID- 17500491
TI  - Trends in the experiences of hospital-employed registered nurses: results from
      three national surveys.
AB  - The comparative results of three national surveys provide the only known source
      of data describing the evolving state of the nursing workforce over time in this
      country. These national random sample surveys expose the harmful effects of a
      lingering shortage of nurses and make plain that much work remains to be done to
      improve the experiences of hospital-employed RNs. At the same time, nurses and
      others involved in hospital patient care should be encouraged by the improvements
      that have been made in recent years, despite the presence of a nursing shortage.

PMID- 17500492
TI  - The impending reimbursement revolution: how to prepare for future APN
      reimbursement.
AB  - Health care reimbursement reform is underway as part of a national effort to
      enhance quality outcomes and bring spiraling health care costs under control.
      Implications of pay-for-performance reimbursement are discussed along with ways
      to prepare for changes in APN reimbursement.

PMID- 17500493
TI  - Care planning efficiency for nursing facilities.
AB  - The project reported here is the first in a series of cost analyses regarding the
      care planning process among 107 facilities. Process-based costing strategies and
      data envelopment analyses identified nursing facilities with efficient and less
      efficient care planning processes. Having more people and more time devoted to
      the care planning process did not assure quality or efficiency. Efficiency varied
      across the nursing facilities and was not related to number of beds, profit
      status, or location; however, Medicare-certified facilities were less likely to
      be efficient.

PMID- 17500494
TI  - Hospitals and philanthropy as partners in funding nursing education.
AB  - The current nursing shortage is complex and varies widely across the country, and
      remedial approaches lack adequate funding from the federal government. Lasting
      remedies must originate from new and different partnerships between multiple
      institutions with complementary missions in these markets. Hospitals as major
      nurse employers and foundations that leverage critical sources of financing have
      a vital role in partnerships. Together they promote and require new
      entrepreneurial skills, innovative educational strategies, and greater
      accountability in meeting area workforce needs.

PMID- 17500495
TI  - The aging workforce: implications for health care organizations.

PMID- 17500496
TI  - Social determinates of health.
AB  - The Aday Theory suggests that vulnerability, or increased risk of poor health
      outcomes, can be modeled by looking at ethical norms and values, health status,
      relative risk, resource availability, and policy (Aday, 2001). This theory looks
      at the tension between the rights and obligations of the individual versus the
      community while also recognizing the impact each has on the other.

PMID- 17500498
TI  - Patient satisfaction and high-reliability organizations: what's the connection?
AB  - So how do we get there? Wagner and Harter (2006) report that it is apparent that
      managers who can make all of this happen view their work beyond profitability.
      Their motivation is created from deeply held beliefs about the solemn
      responsibility of management for those around them. When we view the patient
      satisfaction scores on the public ally reported Web sites, we will have a clear
      view into how the organization has eliminated negative variability and has also
      managed to engage the hearts and minds of their employees and their patients.

PMID- 17500497
TI  - A competency-based approach to expanding the cancer care workforce.

PMID- 17500499
TI  - Keeping up with existing and emerging technologies: an introduction to PDAs.

PMID- 17500500
TI  - Advancing national health care: do we dare consider comprehensive reform again?

PMID- 17500501
TI  - Cost and clinical outcomes of a back injury clinic.

PMID- 17500502
TI  - Transitioning from acute care to ambulatory care.

PMID- 17500503
TI  - Cancer cachexia and targeting chronic inflammation: a unified approach to cancer
      treatment and palliative/supportive care.
AB  - Chronic inflammation often acts as a tumor promoter, resulting in aggressive
      cancerous growth and spread. Many of the same inflammatory factors that promote
      tumor growth also are responsible for cancer cachexia/anorexia, pain,
      debilitation, and shortened survival. A compelling case may be made for mounting
      an attack on inflammation with other anticancer measures at initial diagnosis,
      with the consequent probability of improving both patient quality of life and
      survival. High serum levels of the inflammatory marker C-reactive protein or
      fibrinogen and an elevated white blood cell count correlate with poor prognosis
      and may be used as a prognostic index to establish the need for
      nutritional/metabolic intervention. At the author's institution, a concerted
      effort is being made to screen all newly diagnosed patients with non-small cell
      lung cancer for the presence of nutritional problems, inflammatory markers, and
      related symptoms. Interventions include dietary counseling; nutritional and, if
      warranted, vitamin supplementation; exercise concordant with the patient's
      physical condition; a prescription for omega 3 fatty acids if inflammation is
      present, and general symptom management. To establish the value of early
      nutritional/metabolic intervention, clinical trials are needed that combine
      measures that combat cachexia and inflammation with first-line chemotherapy in
      patients who present with weight loss, fatigue, and deteriorating function.

PMID- 17500504
TI  - Symptom clusters in cancer patients and their relation to EGFR ligand modulation
      of the circadian axis.
AB  - Recent studies in chronobiology and the neurosciences have led to rapid growth in
      our understanding of the molecular biology of the human timekeeping apparatus and
      the neuroanatomic sites involved in signaling between the "master clock" in the
      hypothalamus and other parts of the brain. The circadian axis comprises a central
      clock mechanism and a downstream network of hypothalamic relay stations that
      modulate arousal, feeding, and sleeping behavior. Communication between the clock
      and these hypothalamic signaling centers is mediated, in part, by diffusible
      substances that include ligands of the epidermal growth factor receptor (EGFR).
      Preclinical studies reveal that EGFR ligands such as transforming growth factor
      alpha (TGF-alpha) inhibit hypothalamic signaling of rhythmic behavior; clinical
      observations show that elevated levels of TGF-alpha are associated with fatigue,
      flattened circadian rhythms, and loss of appetite in patients with metastatic
      colorectal cancer. These data support the hypothesis that a symptom cluster of
      fatigue, appetite loss, and sleep disruption commonly seen in cancer patients may
      be related to EGFR ligands, released either by the cancer itself or by the host
      in response to the stress of cancer, and suggest that further examination of
      their role in the production of symptom clustering is warranted.

PMID- 17500505
TI  - Aqua lymphatic therapy in managing lower extremity lymphedema.

PMID- 17500506
TI  - Leveling the playing field: the personal coach program as an innovative approach
      to assess and address the supportive care needs of underserved cancer patients.
AB  - Supportive care addresses informational, social, emotional, spiritual, physical,
      and practical needs that impact the lives of patients and their families.
      Accessing supportive care services is particularly challenging for patients
      facing significant financial and social barriers. This report discusses the
      Personal Coach Program (PCP), which provides specially trained coach navigators
      of supportive care for cancer patients, with special focus on those facing the
      above-mentioned barriers. The PCP was piloted with 63 patients treated at the
      Princess Margaret Hospital in Toronto, Ontario, Canada. Patients faced barriers
      of language, poverty, culture, social isolation, and literacy. Triangulation was
      used to compare and contrast multiple sources of quantitative and qualitative
      evaluation data. Identifying appropriate patients for referral to the PCP was a
      major challenge. Six categories of unmet needs were identified: practical factors
      related to daily living, cancer information, emotional support, interaction with
      the healthcare team, problems with physical health,and factors related to family
      and friends. Many significant barriers to supportive care and unmet needs are not
      identified by time-pressured clinical staff in cancer clinics. The PCP helped to
      identify needs and to improve ability to access services. Participants were
      highly satisfied with the program and believed it had positive implications for
      both physical and emotional health. Based on these results, a demonstration model
      for a supportive-care program is proposed as an integral component of care for
      all cancer patients, including those at risk for underservice.

PMID- 17500507
TI  - Dietary supplement usage by patients with cancer undergoing chemotherapy: does
      prognosis or cancer symptoms predict usage?
AB  - Any interactions between chemotherapeutic drugs and dietary supplements (DS) are
      a concern for oncologists. This study sought to obtain pilot data about the
      prevalence of consumption of DS (which include vitamin/mineral supplements [VS]
      and herbal supplements [HS]) among patients undergoing chemotherapy and to assess
      the relationship between DS consumption and both cancer prognosis and secondary
      cancer symptoms. In this pilot study, data on demographics, DS usage, presence of
      secondary cancer symptoms, and cancer diagnosis and stage were collected on 100
      consecutive patients with gastrointestinal cancer and 40 with breast cancer who
      were receiving active chemotherapy from April 2004 to July 2004. Overall
      prevalence of DS consumption was 52.52% +/- 8.3% (VS,48.2% +/- 8.31%; HS, 23.74%
      +/- 7.07%). Of HS users, 42.42% +/- 16.86% used multiple HS. Factors
      significantly associated with higher consumption of HS were female gender and
      presence of metastasis, fatigue, and cancer pain. No significant associations
      between consumption of DS or HS and age, cancer type, presence of pain, sleep
      problems, or sexual problems were seen. Approximately half of the patients
      undergoing chemotherapy in this pilot survey were using DS, including HS--which
      heralds the potential for drug-supplement interactions and warrants caution.
      Consumption of HS was greater among people having a higher cancer stage and
      symptoms such as fatigue or cancer pain; patients in these subgroups probably
      should be screened actively for DS use. Further studies are needed to confirm
      these results.

PMID- 17500508
TI  - Interface-mediated growth of monodispersed nanostructures.
AB  - This Account focuses on the recent development of interface-mediated growth of
      monodispersed nanostructures in our laboratory. By rationally tuning the chemical
      reactions at various gas-liquid, solid-solid, liquid-liquid, and liquid-solid
      solution interfaces, we could readily synthesize nanostructures such as hollow
      microspheres, core-shell nanoparticles, and monodispersed nanocrystals. These
      advances in interface-mediated synthesis could lead to progress in the
      development of nanocrystal crystallography and encourage some more unique and
      exciting research and applications to nanoscience and nanotechnology.

PMID- 17500510
TI  - Synthesis and in vitro antiplatelet activity of new 4-(1-piperazinyl)coumarin
      derivatives. Human platelet phosphodiesterase 3 inhibitory properties of the two
      most effective compounds described and molecular modeling study on their
      interactions with phosphodiesterase 3A catalytic site.
AB  - The synthesis and in vitro antiplatelet activity significant data of coumarin
      derivatives 5i-x and quinolin-2(1H)-one derivatives 22a,b, as well as the
      corresponding structure-activity relationships are described. The recently
      reported 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin 5f and its
      potent 7-(2-morpholinoethoxy)-substituted new analogue 5u were notably more
      effective inhibitors of pure human platelet PDE3 than milrinone and cilostazol:
      these data were related, through a molecular modeling study, with the molecular
      interactions of the four compounds with the human PDE3A catalytic site.

PMID- 17500511
TI  - Synthesis and biological evaluation of 3-aryl-3-(4-phenoxy)-propionic acid as a
      novel series of G protein-coupled receptor 40 agonists.
AB  - High-throughput screening of a subset of the J&J compound library containing the
      carboxylic acid functional group uncovered a bromophenyl derivative as a moderate
      potent GPR40 agonist. Chemical elaboration of this bromophenyl led to the
      discovery of a novel series of GPR40 agonists with submicromolar potency. Among
      them, 22 and 24 behaved as full agonists when compared to the endogenous GPR40
      ligand linolenic acid in a functional Ca+2 flux assay in HEK cells expressing
      GPR40 receptor. Several GPR40 agonists have also demonstrated the ability to
      induce glucose-mediated insulin secretion in the mouse MIN6 pancreatic beta-cell
      line. Our data supports the hypothesis that GPR40 may play an important role in
      fatty acid-mediated glucose-dependent insulin secretion. Compound 22 exhibited
      good pharmacokinetic profile in rat and may serve as a good candidate for in vivo
      study and may help to determine if GPR40 agonists would be beneficial in the
      treatment of type II diabetes.

PMID- 17500509
TI  - Reconstitution of modular PDK1 functions on trans-splicing of the regulatory PH
      and catalytic kinase domains.
AB  - The serine-threonine protein kinases PDK1 and PKB each contain a pleckstrin
      homology (PH) domain that binds the membrane-bound phosphatidylinositol 3,4,5
      triphosphate [PI(3,4,5)P3] second messenger and is required for PDK1-catalyzed
      phosphorylation and activation of PKB. While X-ray structures have been reported
      for the individual regulatory PH and catalytic kinase domain constructs of both
      PDK1 and PKB, diffraction quality crystals of full length constructs have yet to
      be obtained, likely due to conformational heterogeneity. In developing
      alternative approaches to understanding the potential role of conformational
      dynamics in regulating PKB phosphorylation by PDK1, an efficient in vitro method
      for protein trans-splicing was developed, which utilizes the N- and C-terminal
      split inteins of the gene dnaE from Nostoc punctiforme [(N)NpuDnaE] and
      Synechocystis sp. strain PCC6803 [(C)SspDnaE], respectively. For conjugating the
      regulatory PH domain to the catalytic kinase domain of PDK1, the recombinant
      trans-splicing fusion constructs KINASE(AEY)-(N)NpuDnaE-His6 and GST-His6
      (C)SspDnaE-(CMN)PH were designed, PCR assembled, overexpressed, and affinity
      purified. The cross-reacting (N)NpuDnaE and (C)SspDnaE inteins generated full
      length spliced-PDK1 with kobs = (2.8 +/- 0.3) x 10(-5) s(-1) and with < or =5% of
      any competing trans-cleavage reactions. Spliced-PDK1 was efficiently purified to
      > or =95% homogeneity from the reaction mixture by subsequent His6 affinity and
      ion exchange chromatography steps. In vitro kinase assays and phosphopeptide
      mapping studies confirmed that spliced-PDK1 retained the ability to colocalize
      and selectively phosphorylate Thr-309 of PKBbeta in a PI(3,4,5)P3-dependent
      manner. The high-level production and reconstitution of functional spliced-PDK1
      establishes the feasibility of incorporating domain-specific biophysical probes
      for spectroscopic studies of regulatory PH domain mediated catalytic specificity.

PMID- 17500512
TI  - Fast O2 binding at dicopper complexes containing Schiff-base dinucleating
      ligands.
AB  - A new family of dicopper(I) complexes [CuI2RL](X)2 (R=H, 1X, R=tBu, 2X and R=NO2,
      3X, X=CF3SO3, ClO4, SbF6, or BArF, BArF=[B{3,5-(CF3)2C6H3}4]-), where RL is a
      Schiff-base ligand containing two tridentate binding sites linked by a xylyl
      spacer, has been prepared and characterized, and its reaction with O2 has been
      studied. The complexes were designed with the aim of reproducing structural
      aspects of the active site of type 3 dicopper proteins; they contain two three
      coordinate copper sites and a rather flexible podand ligand backbone. The solid
      state structures of 1ClO4, 2CF3SO3, 2ClO4, and 3BArF.CH3CN have been established
      by single-crystal X-ray diffraction analysis. 1ClO4 adopts a polymeric structure
      in the solid state while 2CF3SO3, 2ClO4, and 3BArF.CH3CN are monomeric. The
      complexes have been studied in solution by means of 1H and 19F NMR spectroscopy,
      which put forward the presence of dynamic processes. 1-3BArF and 1-3CF3SO3 in
      acetone react rapidly with O2 to generate metaestable [CuIII2(mu-O)2(RL)]2+ 1
      3(O2) and [CuIII2(mu-O)2(CF3SO3)(RL)]+ 1-3(O2)(CF3SO3) species, respectively,
      that have been characterized by UV-vis spectroscopy and resonance Raman analysis.
      Instead, reaction of 1-3BArF with O2 in CH2Cl2 results in intermolecular O2
      binding. DFT methods have been used to study the chemical identities and
      structural parameters of the O2 adducts, and the relative stability of the
      CuIII2(mu-O)2 form with respect to the CuII2(mu-eta2:eta2-O2) isomer. The
      reaction of 1X, X = CF3SO3 and BArF, with O2 in acetone has been studied by
      stopped-flow UV-vis exhibiting an unexpected very fast reaction rate
      (k=3.82(4)x10(3) M-1 s-1, DeltaH=4.9+/-0.5 kJ.mol-1, DeltaS=-148+/-5 J.K-1.mol
      1), nearly 3 orders of magnitude faster than in the parent [CuI2(m-XYLMeAN)]2+.
      Thermal decomposition of 1-3(O2) does not result in aromatic hydroxylation. The
      mechanism and kinetics of O2 binding to 1X (X=CF3SO3 and BArF) are discussed and
      compared with those associated with selected examples of reported models of O2
      processing copper proteins. A synergistic role of the copper ions in O2 binding
      and activation is clearly established from this analysis.

PMID- 17500513
TI  - Single-phase titania nanocrystallites and nanofibers from titanium tetrachloride
      in acetone and other ketones.
AB  - Single-phase titania nanomaterials were prepared by autoclaving titanium
      tetrachloride in acetone at 80-140 degrees C. Depending on the molar ratio of
      TiCl4 to acetone (TiCl4/Ac), TiO2 materials with different phases and
      morphologies were obtained. When the TiCl4 concentration was no higher than
      TiCl4/Ac=1/15, single-phase anatase TiO2 nanocrystals in sizes ranging from 4 to
      10 nm were prepared by tuning TiCl4/Ac ratios from 1/90 to 1/15. However, when
      the TiCl4 concentration was high enough (e.g., TiCl4/Ac>or=1/10), single-phase
      rutile TiO2 nanofibers were obtained selectively. The materials were
      characterized comprehensively using X-ray diffraction, transmission electron
      microscopy, Raman spectroscopy, thermogravimetric analysis, and nitrogen
      adsorption measurements. With the aid of GC/MS analysis of organic products in
      the liquid phase, it is shown that the controlled hydrolysis of TiCl4 with water,
      which was in situ generated from the TiCl4-catalyzed aldol condensation reactions
      of acetones, played an important role in the formation of the titania
      nanomaterials. Some of the organic condensates may function to stabilize the
      phase and morphology of the materials. This mechanism was also supported by our
      success in using other ketones as alternatives to acetone in the synthesis.

PMID- 17500514
TI  - Sulfur K-edge XAS and DFT studies on NiII complexes with oxidized thiolate
      ligands: implications for the roles of oxidized thiolates in the active sites of
      Fe and Co nitrile hydratase.
AB  - S K-edge X-ray absorption spectroscopy data on a series of NiII complexes with
      thiolate (RS-) and oxidized thiolate (RSO2-) ligands are used to quantify Ni-S
      bond covalency and its change upon ligand oxidation. Analyses of these results
      using geometry-optimized density functional theory (DFT) calculations suggest
      that the Ni-S sigma bonds do not weaken on ligand oxidation. Molecular orbital
      analysis indicates that these oxidized thiolate ligands use filled high-lying S-O
      pi* orbitals for strong sigma donation. However, the RSO2- ligands are poor pi
      donors, as the orbital required for pi interaction is used in the S-O sigma-bond
      formation. The oxidation of the thiolate reduces the repulsion between electrons
      in the filled Ni t2 orbital and the thiolate out-of-plane pi-donor orbital
      leading to shorter Ni-S bond length relative to that of the thiolate donor. The
      insights obtained from these results are relevant to the active sites of Fe- and
      Co-type nitrile hydratases (Nhase) that also have oxidized thiolate ligands. DFT
      calculations on models of the active site indicate that whereas the oxidation of
      these thiolates has a major effect in the axial ligand-binding affinity of the Fe
      type Nhase (where there is both sigma and pi donation from the S ligands), it has
      only a limited effect on the sixth-ligand-binding affinity of the Co-type Nhases
      (where there is only sigma donation). These oxidized residues may also play a
      role in substrate binding and proton shuttling at the active site.

PMID- 17500516
TI  - Inhibition of Pseudomonas aeruginosa biofilm formation with Bromoageliferin
      analogues.

PMID- 17500517
TI  - Chromophore channeling in the G-protein coupled receptor rhodopsin.

PMID- 17500518
TI  - Probing a fibrillation nucleus directly by deep ultraviolet Raman spectroscopy.

PMID- 17500519
TI  - Phenalenyl-based neutral radical molecular conductors: substituent effects on
      solid-state structures and properties.
AB  - We report the preparation, crystallization, and solid-state characterization of
      cycloheptyl and cyclooctyl-substituted spirobiphenalenyl radicals and the
      corresponding sigma-dimer of the cyclooctyl derivative. The crystal structure
      shows that the cycloheptyl radical (9) is monomeric in the solid state, with the
      molecules packed in an unusual one-dimensional (1-D) fashion that we refer to as
      a pi-chain structure, whereas the cyclooctyl variant exists both as pi-dimer 10
      and sigma-dimer 10d. The neutral radical 9 shows the temperature-independent
      Pauli paramagnetism characteristic of a metal with a magnetic susceptibility,
      chip approximately 4.5x10(-4) emu/mol and is assigned a resonating valence bond
      (RVB) ground state. We highlight the relationship between the magnetic properties
      of the Heisenberg antiferromagnet and the RVB ground state in 1-D and further
      elucidate the electronic structure of this new class of compounds. Magnetic
      susceptibility measurements show that 10 is a diamagnetic pi-dimer, whereas 10d
      is a diamagnetic sigma-dimer. Extended Huckel calculations for 9 indicate that
      the solid is a one-dimensional organic metal with a bandwidth of about 0.4 eV.
      Pressed pellet conductivity measurements indicate values of sigmaRT=1.5x10(-3)
      S/cm for compound 9 and sigmaRT=1.0x10(-6) S/cm for compound 10. The structural
      results and transport properties are discussed in the light of extended Huckel
      theory band structure calculations and DFT investigations of the electronic
      structure of related compounds.

PMID- 17500520
TI  - Synthesis of monodisperse Pt nanocubes and their enhanced catalysis for oxygen
      reduction.

PMID- 17500521
TI  - Beta-elimination and peptide bond hydrolysis: two distinct mechanisms of human
      IgG1 hinge fragmentation upon storage.

PMID- 17500522
TI  - Detection of explosives with a fluorescent nanofibril film.

PMID- 17500523
TI  - Well-defined protein-polymer conjugates via in situ RAFT polymerization.
AB  - Biotechnology, biomedicine, and nanotechnology applications would benefit from
      methods generating well-defined, monodisperse protein-polymer conjugates,
      avoiding time-consuming and difficult purification steps. Herein, we report the
      in situ synthesis of protein-polymer conjugates via reversible addition
      fragmentation chain transfer polymerization (RAFT) as an efficient method to
      generate well-defined, homogeneous protein-polymer conjugates in one step,
      eliminating major postpolymerization purification steps. A water soluble RAFT
      agent was conjugated to a model protein, bovine serum albumin (BSA), via its free
      thiol group at Cys-34 residue. The conjugation of the RAFT agent to BSA was
      confirmed by UV-visible spectroscopy, matrix-assisted laser desorption ionization
      -time of flight (MALDI-TOF), and 1H NMR. BSA-macroRAFT agent was then used to
      control the polymerization of two different water soluble monomers, N
      isopropylacrylamide (NIPAAm) and hydroxyethyl acrylate (HEA), in aqueous medium
      at 25 degrees C. The growth of the polymer chains from BSA-macroRAFT agent was
      characterized by size exclusion chromatography (SEC), 1H NMR, MALDI-TOF, and
      polyacrylamide gel electrophoresis (PAGE) analyses. The controlled character of
      the RAFT polymerizations was confirmed by the linear evolution of molecular
      weight with monomer conversion. The SEC analyses showed no detectable free,
      nonconjugated polymer formation during the in situ polymerization. The efficiency
      of BSA-macroRAFT agent to generate BSA-polymer conjugates was found to be ca. 1
      by deconvolution of the SEC traces of the polymerization mixtures. The structural
      integrity and the conformation-related esterase activity of BSA were found to be
      unaffected by the polymerization conditions and the conjugation of the polymer
      chain. BSA-poly(NIPAAm) conjugates showed hybrid temperature-dependent phase
      separation and aggregation behavior. The lower critical solution temperature
      values of the conjugates were found to increase with the decrease in molecular
      weight of poly(NIPAAm) block conjugated to BSA.

PMID- 17500524
TI  - Beta-styryl- and beta-aryl-beta-alanine products of phenylalanine aminomutase
      catalysis.

PMID- 17500525
TI  - Challenging the prediction of anionogenic ferromagnetism for Rb4O6.

PMID- 17500526
TI  - A self-assembled DNA bipyramid.

PMID- 17500528
TI  - Soil calcium and pH monitoring sensor system.
AB  - An agrarian sensorial system based on temperature, moisture, and all solid-state
      ion-selective potentiometric sensors was developed with the objective of
      monitoring the behavior of H+ and Ca2+ ions in soil and in real conditions,
      contributing with a new tool that tries to complement the current precision
      agriculture technology. The evaluation of the sensorial system to pH monitoring
      presented a good correlation between the results obtained by the system and the
      standard methodology, allowing us to notice the soil buffer capacity at different
      soil depths. With regard to calcium, the sensor system also presented an
      agreement between its results and those obtained by flame atomic absorption
      spectrometry, using a calibration model based on multiple linear regressions that
      allows the correct determination of Ca2+ concentrations in soil depths where the
      relative moisture is different. In this way, using well-known potentiometric
      sensors in a complex, discontinued, and heterogeneous matrix, such as soil, the
      sensorial system proved to be a useful task for agrochemical field applications.

PMID- 17500529
TI  - A biophysical investigation on the binding and controlled DNA release in a
      cetyltrimethylammonium bromide-sodium octyl sulfate cat-anionic vesicle system.
AB  - The interactions between cat-anionic (an acronym indicating surfactant aggregates
      (micelles and vesicles) formed upon mixing cationic and anionic surfactants in
      nonstoichiometric amounts) vesicles and DNA have been the subject of intensive
      studies because of their potential applications in biomedicine. Here we report on
      the interactions between DNA and cetyltrimethylammonium bromide (CTAB)-sodium
      octyl sulfate (SOS) cat-anionic vesicles. The study was performed by combining
      dielectric relaxation spectroscopy, circular dichroism, dynamic light scattering,
      ion conductivity, and molecular biology techniques. DNA is added to positively
      charged vesicles until complete charge neutralization of the complex and
      formation of lipoplexes. This occurs when the mole ratio between the phosphate
      groups of DNA and positive charges on the vesicle is about 1.8. Above this
      threshold the nucleic acid in excess remains free in solution. This very
      interesting new result shows that anionic surfactants are not expelled upon
      saturation, and therefore, no formation of micelles occurs. Furthermore, vesicle
      bound DNA can be released in its native form, as confirmed by dielectric
      spectroscopy and circular dichroism measurements. The nucleic acid is released
      upon addition of SOS, which competes with the phosphate groups of the DNA: this
      results in the demolition of the CTAB-SOS cat-anionic vesicles. These results
      indicate the possibility of a controlled DNA release and might be of interest in
      biomedicine.

PMID- 17500530
TI  - Cell attachment to microcarriers affects growth, metabolic activity, and culture
      productivity in bioreactor culture.
AB  - It is not well understood how changes from suspension to microcarrier cultures
      affect cell growth, metabolism, and yield of recombinant proteins. To investigate
      the effects of culture conditions on cell characteristics, fed-batch bioreactor
      cultures were performed under different culture conditions (suspension cultures,
      cultures attached to Cytodex 3 and Cytopore 1 microcarriers) using two different
      Chinese hamster ovary cell lines producing either secreted human placental
      alkaline phosphatase (TR2-255) or tissue plasminogen activator (CHO 1-15-500). In
      controlled, agitated bioreactors, suspension cultures reached cell densities and
      product titers higher than those in microcarrier cultures, in contrast to the
      results in static flask cultures. Growth and metabolic activities showed similar
      trends in suspension and microcarrier culture regardless of cell line. However,
      the responses of the specific productivities to the different culture conditions
      differed significantly between the cell lines.

PMID- 17500531
TI  - Increased beta-carotene production in recombinant Escherichia coli harboring an
      engineered isoprenoid precursor pathway with mevalonate addition.
AB  - When pT-LYCm4 containing lycopene synthetic genes was co-transformed with pSUcrtY
      or pSHcrtY containing crtY gene of Pantoea ananatis (P. ananatis) or Pantoea
      agglomerans (P. agglomerans), beta-carotene productions of 36 and 35 mg/L were
      obtained, respectively. No lycopene was detected in the beta-carotene production
      culture. pT-HB, constructed by addition of P. ananatis crtY gene into pT-LYCm4,
      was used for co-transformation with pSdxs and pSSN12Didi, which increased
      isopentenyl diphosphate and dimethylallyl diphosphate synthesis. beta-Carotene
      production significantly increased 1.5-fold (51 mg/L) with the amplification of
      the dxs gene through pSdxs and 4-fold (135 mg/L) with the mevalonate bottom
      pathway of pSSN12Didi in the presence of 3.3 mM mevalonate. The pT-DHB,
      constructed by integrating the dxs gene into pT-HB, was used for cotransformation
      of Escherichia coli (E. coli) harboring pSSN12Didi, resulting in beta-carotene
      production of 141 mg/L. Recombinant E. coli harboring pT-DHB and pSSN12Didi was
      used to maximize beta-carotene production by adjusting the available amounts of
      glycerol, a carbon source, and mevalonate, the precursor of the mevalonate bottom
      pathway. When recombinant E. coli was given 16.5 mM mevalonate and 2.5% (w/v)
      glycerol, beta-carotene production of 503 mg/L in concentration and 49.3 mg/g DCW
      in content was obtained at 144 h, which was the highest level of carotenoid
      production in E. coli ever reported in the literature.

PMID- 17500532
TI  - Fast comprehensive two-dimensional gas chromatography with cryogenic modulation.
AB  - The fast separation of a mixture of 29 compounds by using comprehensive two
      dimensional gas chromatography is reported. Capillary column sets with shorter
      lengths and smaller inner diameter in both the first and second dimensions have
      been tested, for both fast chiral and achiral separations. Fast chiral
      separations, which included enantiomer separations of limonene, linalool,
      citronellol, and alpha-isomethylionone, were achieved within 23 min, which
      corresponds to approximately 2-fold faster than analyses under conditions
      previously considered as normal. Fast achiral separations, which do not have the
      restriction of requiring a minimum quality of chiral resolution, were obtained
      within 5 min, which is markedly faster than separations on the normal column set
      under conditions more commonly employed. The achiral fast GC x GC method used a 5
      m x 0.1 mm i.d. first dimension column, interfaced to a 0.3 m x 0.05 mm i.d.
      second column, with temperature program rate of 35 degrees C.min-1; a modulation
      period of 1 s was employed. Peak widths at baseline on the first column were a
      little over 1 s, while modulated peak widths at half-height recorded with a flame
      ionization detector operating at 200 Hz were approximately 30 ms. The benefits
      and limitations of GC x GC for fast chiral and achiral separations are reported
      and discussed.

PMID- 17500533
TI  - Powder X-ray thermodiffraction study of mirabilite and epsomite dehydration.
      Effects of direct IR-irradiation on samples.
AB  - This paper investigates the thermal and irradiation-dependent dehydration and
      kinetics occurring in Na2SO4.10H2O (mirabilite) and MgSO4.7H2O (epsomite) at room
      conditions by using powder X-ray thermodiffraction. An improved version of a
      first optically stimulated X-ray diffractometer prototype was used. Specific
      software for the thermodiffraction study was developed (XPowder PLUS) and a
      filter inserted between the lamp (heating system) and the sample. The results
      show that these salts are thermal and irradiation sensitive. The temperature and
      kinetic rates of the salt conversions differed depending on direct exposure to
      high-intensity radiation (photodehydration) or whether the radiation was blocked
      by the filter (thermodehydration). In general, radiation-induced dehydration
      triggers the transformation at lower temperature and accelerates the kinetic
      reaction more than when the filter is used. Mirabilite dehydration starts with
      the initial radiation impacts, unlike epsomite. Thermodehydration and
      photodehydration of mirabilite is a non-isothermal reaction occurring through an
      amorphous-mediated step. Radiation damage in epsomite leads to isothermal
      dehydration, whereas non-isothermal dehydration occurs when epsomite is thermally
      damaged. In both cases, no amorphous material was observed. Because of the weaker
      bond between cation and oxygen atom in mirabilite, its thermal and radiation
      stability is lower than in epsomite. These results have important implications
      for the prevention of salt weathering of porous materials found in the cultural
      heritage.

PMID- 17500534
TI  - Shotgun analysis of integral membrane proteins facilitated by elevated
      temperature.
AB  - The beneficial effects on peak selectivity and resolution of conducting liquid
      chromatography (LC) at elevated temperature (e.g., 30-80 degrees C) are generally
      well-known; however, its importance for peptide recovery is not nearly as well
      recognized. This report demonstrates that microLC analysis of membrane proteomic
      samples significantly benefits from the application of heat. Enriched membrane
      and membrane-embedded peptides (the latter obtained by membrane shaving) were
      analyzed by microLC-tandem mass spectrometry (MS/MS) from 20 to 60 degrees C
      using a standard reversed-phase material. Maximal protein and hydrophobic peptide
      recovery was obtained at 60 degrees C. The membrane-shaving method employed, a
      recently optimized version of the high pH/proteinase K protocol, provided
      significant integral membrane protein enrichment: 98% of identified proteins were
      predicted to have at least one transmembrane domain (87% to have at least three),
      and 68% of peptides were predicted to contain transmembrane segments. Analysis of
      this highly enriched sample at elevated temperature increased protein
      identifications by 400%, and peptide identifications by 500%, as compared to room
      temperature separation. Given that most microLC-MS/MS analyses are currently
      conducted at room temperature, the findings described herein should be of
      considerable value for improving the comprehensive study of integral membrane
      proteins.

PMID- 17500535
TI  - LC-MS/MS method for confirmation of recombinant human erythropoietin and
      darbepoetin alpha in equine plasma.
AB  - Recombinant human erythropoietin (rhEPO) and darbepoetin alpha (DPO) are protein
      based drugs for the treatment of anemia by stimulating red blood cell production.
      Consequently, they are abused in human and equine sports. To deter their abuse in
      the horse racing industry, a sensitive and reliable method for confirmation of
      these agents in equine plasma has been in urgent need. Such a method by LC-MS/MS
      is described in this paper. The method involved analyte enrichment by
      immunoaffinity separation using anti-rhEPO antibody linked to magnetic beads,
      digestion by trypsin, and analysis by LC-MS/MS. Two specific proteotypic
      peptides, 46VNFYAWK52 and 144VYSNFLR150 from rhEPO and DPO were employed for
      confirmation of the analytes based on chromatographic retention times and major
      product ions. The limit of confirmation of this method was 0.2 ng/mL, and the
      limit of detection was 0.1 ng/mL for rhEPO and DPO in equine plasma. This method
      was successful in confirming the presence of rhEPO and DPO in plasma samples
      collected from research horses to which rhEPO or DPO was administered and from
      racehorses following competition and in noncompetition samples in North America.
      To our knowledge, this is the first LC-MS method with adequate sensitivity and
      specificity in providing unequivocal confirmation of rhEPO and DPO in equine
      plasma samples. This method provides a powerful enforcement tool that was lacking
      in the fight against the abuse of rhEPO and DPO in the horse racing industry.

PMID- 17500536
TI  - Molecular analysis of native tissue and whole oils by infrared laser mass
      spectrometry.
AB  - We have employed infrared laser desorption ionization orthogonal time-of-flight
      mass spectrometry (IR-LDI-o-TOF-MS) to generate molecular ion profiles directly
      from native tissue and from whole oils. The method requires little sample
      preparation besides an eventual dissection of the areas of interest and drying of
      particularly water-rich samples. The lateral resolution of the analysis is on the
      order of the laser focal diameter, and in the third dimension, defined by the
      depth of material ejection, a few to 10 microm per laser pulse. Various types of
      small molecules are readily detected from minute volumes of sample. Among these
      are carbohydrates, phospholipids, triglycerides, and flavonoids. Substantially
      different molecular profiles were recorded from different areas of a single
      strawberry seed.

PMID- 17500537
TI  - Method for quantitative protein-ligand affinity measurements in compound
      mixtures.
AB  - This manuscript describes an affinity selection-mass spectrometry (AS-MS) method
      for quantitative protein-ligand binding affinity (Kd) measurements in large
      compound libraries. The ability of a titrant ligand to displace a target-bound
      library member-as measured by MS-reveals the affinity ranking of the mixture
      component relative to "internal affinity calibrants", compounds of known affinity
      for the target. This technique does not require that the precise concentration of
      each ligand is known; therefore, unpurified products of mixture-based
      combinatorial synthesis may be used for affinity optimization and developing
      structure-activity relationships. The method is demonstrated for a series of
      ligands to the important oncology target CDK2 that were discovered by AS-MS
      screening of combinatorial libraries against the basal form of the protein. AS-MS
      displacement curves for select hits were acquired over a range of compound
      concentrations, confirming that binding affinity measurement results are
      concentration-insensitive. These hits were evaluated in pools of purified
      compounds to verify the method's applicability to hit triage in large chemical
      libraries. The method was further tested using unpurified, mixture-based
      combinatorial libraries of >1000 compounds, yielding results that mirror those
      obtained from mixtures of purified compounds. The technique was then used to
      identify optimized CDK2 ligands from compound mixtures, quantitatively measure
      their affinities, and establish structure-activity relationships among these drug
      leads.

PMID- 17500538
TI  - An optimized purification and reconstitution method for the MscS channel:
      strategies for spectroscopical analysis.
AB  - The mechanosensitive channel of small conductance (MscS) plays a critical role in
      the osmoregulation of prokaryotic cells. The crystal structure of MscS revealed a
      homoheptamer with three transmembrane segments and a large cytoplasmic domain. It
      has been suggested that the crystal structure depicts an open state, but its
      actual functional conformation remains controversial. In the pursuit of
      spectroscopical approaches to MscS gating, we determined that standard
      purification methods yield two forms of MscS, with a considerable amount of
      unfolded channel. Here, we present an improved high-yield purification method
      based on Escherichia coli expression and a biochemical characterization of the
      reconstituted channel, optimized to yield approximately 4 mg of a single
      monodisperse product. Upon reconstitution into lipid vesicles, MscS is unusually
      prone to lateral aggregation depending on the lipid composition, particularly
      after sample freezing. Strategies for minimizing MscS aggregation in two
      dimensions for spectroscopic analyses of gating have been developed.

PMID- 17500539
TI  - Systematic solution-phase parallel synthesis of active vitamin D3 analogs with
      elongated side chains and their cell differentiation activities.
AB  - Side-chain elongation of active vitamin D3 is acknowledged as a structural
      modification to enhance its cell differentiation activity; however, the
      comprehensive structure-activity relationship (SAR) as a result of this
      modification has not been reported. To clarify the SAR, we synthesized six
      analogs systematically elongated at the 24-position, 26,27-position, or both by
      methylene (normal A-ring series 1a-f) in a facile parallel solution-phase
      synthesis. Using parallel synthesis, we expanded the side chain-elongation study
      into two 19-exomethylene analog series: 19-nor-A-ring (4a-f) and 2-methylene-19
      nor-A-ring (5a-f). In the 19-nor-A-ring analog series, the SAR induced by side
      chain elongation was similar to the normal A-ring analog series, but in the 2
      methylene-19-nor-A-ring series, the SAR was unique.

PMID- 17500540
TI  - Vertical and adiabatic ionization potentials of fluorinated, chlorinated, and
      chlorofluorinated ethylenes using G2 and G3 theories.
AB  - Adiabatic ionization potentials (AIPs) and vertical ionization potentials (VIPs)
      for all fluorinated, chlorinated, and chlorofluorinated ethylenes have been
      determined by ab initio computations. The calculated AIPs give a mean absolute
      deviation of 0.014 eV at G2 and 0.015 eV at G3 theories compared to experimental
      values. We have estimated AIPs (in eV) for AIP ((E)-CHCl=CFCl) = 9.59, AIP ((Z)
      CHCl=CFCl) = 9.60, AIP (CCl2=CFCl) = 9.42, and AIP (CHF=CCl2) = 9.65.
      Furthermore, our calculated AIPs values of 9.58 eV for (Z)-CFCl=CFCl and 9.56 eV
      for (E)-CFCl=CFCl are very different from the experimental data of 10.2 eV. VIPs
      are calculated by Koopmans's theorem with HF methodology and by G2 and G3
      theories. Koopmans's theorem fails in giving a good description of the behavior
      of the VIPs for fluoroethylenes. Furthermore, significant improvement in the
      results is observed by the mean absolute deviation from experimental data on the
      computed values (0.242 eV using the 6-311+G(3df,2p) basis set and 0.248 eV using
      the GTlarge basis set, compared with 0.049 eV at G2 and 0.045 eV at G3 theories)
      when orbital relaxation and changes in electronic correlation and zero-point
      energies are taken into account. Our estimated VIPs values calculated by G3
      theory (in eV) are VIP ((E)-CHCl=CFCl) = 9.89, VIP ((Z)-CHCl=CFCl) = 9.90, VIP
      ((E)-CFCl=CHF)= 10.26, VIP ((Z)-CFCl=CHF) = 10.25, VIP ((E)-CFCl=CFCl) = 9.93,
      VIP ((Z)-CFCl=CFCl) = 9.96, VIP (CCl2=CFCl) = 9.71, VIP (CF2=CHCl) = 10.19, VIP
      (CHF=CCl2) = 9.96, VIP (CH2=CFCl) = 10.32, VIP ((Z)-CHCl=CHF) = 10.16, and VIP
      ((E)-CHCl=CHF) = 10.16. Furthermore, the variation of the VIPs and AIPs with the
      increase in the number of halogen atoms in the molecules presents different
      patterns to chloroethylenes and fluoroethylenes.

PMID- 17500541
TI  - Concerted and stepwise reaction mechanisms for the addition of ozone to
      acetylene: a computational study.
AB  - The mechanism of the reaction between acetylene and ozone to form a primary
      ozonide (POZ) in the gas phase has been studied theoretically. The concerted
      pathway, HCCH + O3 --> POZ, proceeds via a biradicaloid transition state TS0. The
      stepwise pathway is a three-step reaction, HCCH + O3 --> M1 --> M2 --> POZ,
      involving two biradical TSs and two biradical intermediates M1 and M2. The
      segment of the global potential energy surface (PES) for the concerted pathway is
      characterized as a R-PES, which is obtained from the restricted (R) density
      functional theory and Hartree-Fock-based methods. The RDFT and RHF solutions of
      TS0 and O3 are unstable toward spin-symmetry breaking. The wave function
      instability for TS0 and O3 results in a discontinuity between the R-PES and the
      region of the global PES encompassing the biradical TSs and the intermediates of
      the stepwise pathway, which are characterized with unrestricted (U) methods. The
      global PES is characterized separately as an U(R)-PES using a combination of the
      R and U methods. Several different values of barriers for the concerted pathway
      and the energy of concert (Ec) can be estimated due to complications arising from
      the discontinuity between the R- and the U(R)-PES and the existence of two
      different RDFT and UDFT O3 equilibrium geometries. RCCSD(T)//RDFT predicts a
      barrier of 8.2 kcal/mol. U(R)CCSD(T)/U(R)DFT predicts a barrier of 13.8 kcal/mol
      for the concerted and 15.3 kcal/mol for the stepwise pathway. Comparison between
      the R-PES barrier to the concerted pathway and the U(R)-PES barrier to the
      stepwise pathway suggests the former to be the only significant mechanism.
      Consideration of the energy difference between TS1, the TS for the first step of
      the stepwise mechanism, and TS0 within the global PES leads to a significantly
      smaller Ec. Geometry optimization with CASSCF and energy point calculations with
      MRMP2 are employed to characterize TS0 and TS1. MRMP2//CASSCF predicts the energy
      level of TS1 to be higher than that of TS0 by 2 kcal/mol. Analysis of
      experimental and computational data based on the low estimate of Ec shows that
      the possibility of the stepwise pathway being a secondary channel at elevated
      temperatures cannot be ruled out.

PMID- 17500542
TI  - Epitaxial growth of InN films by molecular-beam epitaxy using hydrazoic acid
      (HN3) as an efficient nitrogen source.
AB  - Epitaxial InN films have been successfully grown on c-plane GaN template by gas
      source molecular-beam epitaxy with hydrazoic acid (HN3) as an efficient nitrogen
      source. Results in residual-gas analyzer show that the HN3 is highly dissociated
      to produce nitrogen radicals and can be controlled in the amounts of active
      nitrogen species by tuning HN3 pressure. A flat and high-purity InN epifilm has
      been realized at the temperature near 550 degrees C, and a growth rate of 200
      nm/hr is also achieved. Moreover, the epitaxial relationship of the InN(002) on
      the GaN(002) is reflected in the X-ray diffraction, and the full-width at half
      maximum of the InN(002) peak as narrow as 0.05 degrees is related to a high
      quality crystallinity. An infrared photoluminescence (PL) emission peak at 0.705
      eV and the integrated intensity increasing linearly with excitation power suggest
      that the observed PL can be attributed to a free-to-bound recombination.

PMID- 17500543
TI  - Can the four-coordinated, penta-valent oxygen in hydroxide water clusters be
      detected through experimental vibrational spectroscopy?
AB  - In this study, we construct the hydroxide water cluster, OH-(H2O)6, that (a)
      could support a stable hydroxide ion with a four-coordinated (pentavalent)
      hydroxide oxygen and (b) displays hydroxide ion migration. We study the energetic
      stability and dynamical evolution of the system at different internal
      temperatures and analyze the corresponding "dynamically averaged" vibrational
      density of states to discuss the conditions under which the pentavalent oxygen
      may be observed using vibrational action spectroscopy. We also provide an
      alternate hydroxide migration mechanism.

PMID- 17500544
TI  - Photoactivity and UV absorption spectroscopy of RCo(CO)4 (R = H, CH3)
      organometallic complexes.
AB  - The photoactivity of RCo(CO)4 (R = H, CH3) complexes has been investigated and
      compared by means of state correlation diagrams connecting the low-lying singlet
      (1)E (d(Co) --> sigma*(Co-R) and d(Co) --> pi*(CO)) and (1)A1 (d(Co) --> pi*(CO))
      electronic states accessible through UV irradiation, and the low-lying triplet
      states ((3)E and (3)A1), to the corresponding states of the primary products R +
      Co(CO)4 and CO(ax) + RCo(CO)3. The electronic absorption spectra have been
      calculated by time-dependent wave packet propagations on two-dimensional
      potential energy surfaces describing both channels of dissociation, namely the
      homolysis of the R-Co and the CO(ax)-Co bonds. It is shown that the absorption
      spectrum of HCo(CO)4 is characterized by two peaks; the most intense peaks for
      each set are located respectively at 42,659 and 45,001 cm(-1). The CH(3)Co(CO)4
      absorption spectrum also gives two sets of signals with maximum intensities found
      at 42,581 and 51,515 cm(-1). These bands for both molecules are assigned to the
      two metal-to-ligand-charge-transfer (MLCT; d(Co) --> pi*(CO)) states. Three
      photoactive states have been determined in both molecules, namely the singlet
      metal-to-sigma-bond-charge-transfer (MSBCT) states (a(1)E and b(1)E),
      simultaneously dissociative for both the homolysis of CO and the R-Co bond, and
      the (3)A1 (sigma(Co-R) --> sigma*(Co-R)), dissociative along the R-Co bond.

PMID- 17500545
TI  - UV near-resonance Raman spectroscopic study of 1,1'-bi-2-naphthol solutions.
AB  - The normal and UV near-resonance Raman (UVRR) spectra of 1,1'-bi-2-naphthol (BN)
      in basic solution were measured and analyzed. Density functional theory (DFT)
      calculations were carried out to study the ground state geometry structure,
      vibrational frequencies nu, off-resonance Raman intensities I, and depolarization
      ratios rho of 1,1'-bi-2-naphtholate dianion (BN(2-)). On the basis of the
      calculated and experimental results of nu, I, and rho, the observed Raman bands
      were assigned in detail. The 1612 cm(-1) Raman band of BN in basic solution was
      found dramatically enhanced in the UV resonance Raman spectrum in comparison with
      the normal Raman spectrum. Analyzing the depolarization ratios of the 1366 and
      1612 cm(-1) bands in the RR spectra manifests that both the symmetric and
      antisymmetric parts of transition polarizabilities contribute to the 1366 cm(-1)
      band, but that only the symmetric part contributes to the 1612 cm(-1) band.

PMID- 17500546
TI  - Vibrational spectroscopy of protonated imidazole and its complexes with water
      molecules: ab initio anharmonic calculations and experiments.
AB  - The results of anharmonic frequency calculations on neutral imidazole (C3N2H4,
      Im), protonated imidazole (ImH+), and its complexes with water (ImH+)(H2O)n, are
      presented and compared to gas phase infrared photodissociation spectroscopy
      (IRPD) data. Anharmonic frequencies are obtained via ab initio vibrational self
      consistent field (VSCF) calculations taking into account pairwise interactions
      between the normal modes. The key results are: (1) Prediction of anharmonic
      vibrational frequencies on an MP2 ab initio potential energy surface show
      excellent agreement with experiment and outstanding improvement over the harmonic
      frequencies. For example, the ab initio calculated anharmonic frequency for
      (ImH+)(H2O)N2 exhibits an overall average percentage error of 0.6% from
      experiment. (2) Anharmonic vibrational frequencies calculated on a semiempirical
      potential energy surface fitted to ab initio harmonic data represents
      spectroscopy well, particularly for water complexes. As an example, anharmonic
      frequencies for (ImH+)H2O and (ImH+)(H2O)2 show an overall average deviation of
      1.02% and 1.05% from experiment, respectively. This agreement between theory and
      experiment also supports the validity and use of the pairwise approximation used
      in the calculations. (3) Anharmonic coupling due to hydration effects is found to
      significantly reduce the vibrational frequencies for the NH stretch modes. The
      frequency of the NH stretch is observed to increase with the removal of a water
      molecule or replacement of water with N2. This result also indicates the ability
      of the VSCF method to predict accurate frequencies in a matrix environment. The
      calculation provides insights into the nature of anharmonic effects in the
      potential surface. Analysis of percentage anharmoncity in neutral Im and ImH+
      shows a higher percentage anharmonicity in the NH and CH stretch modes of neutral
      Im. Also, we observe that anharmonicity in the NH stretch modes of ImH+ have some
      contribution from coupling effects, while that of neutral Im has no contribution
      whatsoever from mode-mode coupling. It is concluded that the incorporation of
      anharmonic effects in the calculation brings theory and experiment into much
      closer agreement for these systems.

PMID- 17500547
TI  - Quantitative computational thermochemistry of transition metal species.
AB  - The correlation consistent Composite Approach (ccCA), which has been shown to
      achieve chemical accuracy (+/-1 kcal mol-1) for a large benchmark set of main
      group and s-block metal compounds, is used to compute enthalpies of formation for
      a set of 17 3d transition metal species. The training set includes a variety of
      metals, ligands, and bonding types. Using the correlation consistent basis sets
      for the 3d transition metals, we find that gas-phase enthalpies of formation can
      be efficiently calculated for inorganic and organometallic molecules with ccCA.
      However, until the reliability of gas-phase transition metal thermochemistry is
      improved, both experimentally and theoretically, a large experimental training
      set where uncertainties are near +/-1 kcal mol-1 (akin to commonly used main
      group benchmarking sets) remains an ambitious goal. For now, an average deviation
      of +/-3 kcal mol-1 appears to be the initial goal of "chemical accuracy" for ab
      initio transition metal model chemistries. The ccCA is also compared to a more
      robust but relatively expensive composite approach primarily utilizing large
      basis set coupled cluster computations. For a smaller training set of eight
      molecules, ccCA has a mean absolute deviation (MAD) of 3.4 kcal mol-1 versus the
      large basis set coupled-cluster-based model chemistry, which has a MAD of 3.1
      kcal mol-1. However, the agreement for transition metal complexes is more system
      dependent than observed in previous benchmark studies of composite methods and
      main group compounds.

PMID- 17500551
TI  - Dicynthaurin (ala) monomer interaction with phospholipid bilayers studied by
      fluorescence leakage and isothermal titration calorimetry.
AB  - The interaction of the antimicrobial peptide dicynthaurin (ala) monomer with
      model membranes of zwitterionic and negatively charged lipids and mixtures
      thereof was studied by means of isothermal titration calorimetry (ITC),
      fluorescent leakage, and dynamic light scattering (DLS) measurements. For the ITC
      analysis, we have applied the surface partitioning equilibrium model which shows
      that the interaction is predominately driven by hydrophobic effects (Kb between 2
      x 10(4) and 1 x 10(5) M(-1)). Under low salt conditions, the enhanced
      electrostatic interaction leads to larger peptide concentrations immediately
      above the vesicle surface, which initiates the insertion of the peptide into the
      bilayer more effectively. Fluorescent leakage measurements have shown a fast
      leakage of the fluorescent dye within seconds after peptide addition. The
      analysis of the leakage kinetics was performed in terms of an initial pore
      formation model (up to t = 1000 s) that takes the reversible surface aggregation
      of bound peptide monomers into account. From this analysis, a minimum aggregation
      number of n = 7 +/- 2 per pore is obtained.

PMID- 17500550
TI  - The effects of N-terminal part modification of arginine vasopressin analogues
      with 2-aminoindane-2-carboxylic acid: a highly potent V2 agonist.
AB  - In this study we present the synthesis and some pharmacological properties of
      nine new analogues of arginine vasopressin modified in the N-terminal part of the
      molecule with 2-aminoindane-2-carboxylic acid (Aic). The peptides were tested for
      their in vitro uterotonic and in vivo pressor and antidiuretic activities. One of
      the new peptides, [Mpa1,Aic2,Val4,D-Arg8]VP, exhibited an antidiuretic activity
      similar to that of [Mpa1,D-Arg8]VP, thus being one of the most potent
      antidiuretic vasopressin analogues reported to date.

PMID- 17500552
TI  - Microfluidic thermodynamics of the shift in thermal stability of DNA duplex in a
      microchannel laminar flow.
AB  - This paper reports the shift in thermal stability of DNA duplex and its
      thermodynamics spectroscopically, caused by stretching and orientation of DNA
      strands in a microchannel laminar flow. For direct spectroscopic measurement of
      the microchannel, we prepared an in-house temperature-controllable microchannel
      type flow cell. The melting curves of DNA oligomers in a microchannel laminar
      flow were measured. For DNA oligomers with more than 10 base pairs, the melting
      curve shifted to the high-temperature side with higher flow speed. However, for 8
      base-pair DNA oligomers, a change in the melting profile was not observed in
      batchwise and microchannel flows. We undertook microfluidic thermodynamic
      analysis to elucidate details of the shift in thermal stability of the DNA duplex
      in a microchannel laminar flow. Enthalpy-entropy compensation is applicable to
      the microfluidic thermal stability shift. We studied the relationships between
      the enthalpy-entropy compensation and DNA strand length or flow speed. Results
      showed that the enthalpy-entropy compensation was influenced by both DNA strand
      length and flow speed, and the penalties of enthalpy were 2-12% greater than the
      benefits of entropy.

PMID- 17500553
TI  - Comparative study on polymer light-emitting devices based on blends of
      polyfluorene and 4,7-di-2-thienyl-2,1,3-benzothiadiazole with devices based on
      copolymer of the same composition.
AB  - The small molecule 4,7-di-2-thienyl-2,1,3-benzothiadiazole (DBT) dye has been
      synthesized and blended into blue-emitting polyfluorene as a host. The
      photophysics of the blend films and electroluminescence device performance was
      compared with that from polyfluorene-co-4,7-di-2-thienyl-2,1,3-benzothiadiazole
      (PFO-DBT) copolymer of the same molar composition, with DBT incorporated
      covalently into the polyfluorene backbone. The role of intra- and interpolymer
      chain interaction and energy transfer in the polymer light-emitting devices are
      discussed. On the basis of the direct comparison of blend and copolymer from the
      same molecular composition, we can draw the conclusion that, in conjugated
      polymers, intrachain energy transfer along the polymer backbone is more efficient
      than that via interchain interaction and plays a more important role in polymer
      light-emitting devices.

PMID- 17500554
TI  - Penetration and saturation of lysozyme in phospholipid bilayers.
AB  - We show that the combination of X-ray reflectivity, tryptophan fluorescence
      spectrum, and fluorescence quenching by bromine provides a useful tool to probe
      the location of lysozyme in lipid bilayers. To this end, we prepare lamellar
      complexes composed of phospholipids and lysozyme on solid surfaces using a
      solution-casting method. The proteins lie spontaneously between adjacent bilayers
      in the complexes. The results indicate that lysozyme may penetrate into the lipid
      bilayers. But the penetration depth is very shallow, and the tryptophan residues
      do not penetrate beyond the interface between the hydrocardon core and the
      headgroup region of the lipid bilayer. The penetration becomes saturated when
      more proteins are incorporated into the lamellar complex. The excess proteins
      stay in the interlamellar aqueous layers.

PMID- 17500555
TI  - Molecular exchange through the vesicle membrane of siloxane surfactant in
      water/glycerol mixed solvents.
AB  - The effect of glycerol on the permeability of vesicle membranes of a siloxane
      surfactant, the block copolymer polyethyleneoxide-b-polydimethylsiloxane
      polyethyleneoxide, (EO)15-(DMS)15-(EO)15, was studied with freeze-fracture
      transmission electron microscopy (FF-TEM) and pulsed-field gradient nuclear
      magnetic resonance (PFG-NMR) spectroscopy. The FF-TEM results show that, in pure
      water, the surfactant can form small vesicles with diameters of less than 25 nm,
      as well as a few multilamellar vesicles with diameters larger than 250 nm.
      Gradual substitution of water with glycerol to a glycerol content of 40% leads to
      significant structural transformations: small vesicles are gradually swollen, and
      large multilamellar vesicles disappear. A glycerol content of 60% results in the
      complete disintegration of the vesicles into membrane fragments. PFG-NMR
      measurements indicate that the vesicle membrane does not represent an effective
      barrier for water molecules on the NMR time scale; hence, the average residence
      time of water in the encapsulated state is below tau b = 2 ms. In contrast, the
      average residence time of glycerol molecules in the encapsulated state can be as
      large as tau b = 910 ms. The permeability of the vesicle membrane increases with
      increasing glycerol concentration in the solvent: At a concentration of 40%, the
      residence time tau b is lowered to approximately 290 ms. After vesicle
      destruction at higher glycerol concentrations, a small glycerol fraction is still
      bound by membrane fragments that are formed after the disintegration of the
      vesicles.

PMID- 17500556
TI  - Electric-field-induced spin accumulation in polymer light-emitting diodes.
AB  - An electric-field-induced spin accumulation phenomenon is presented for
      electroluminescent conjugated polymers as light-emitting diodes (LEDs). When an
      electric field is applied along a polymer chain and exceeds a critical value, it
      quenches the luminescence and dissociates the singlet exciton into two carriers
      with opposite spin signs. Simultaneously, the field drives these two opposite
      spin carriers to move in opposite directions, leading to spin accumulation at the
      two ends of the organic material LED, which can be detected through Kerr rotation
      microscopy.

PMID- 17500557
TI  - Kinetic separation of hexane isomers by fixed-bed adsorption with a microporous
      metal-organic framework.
AB  - A three-dimensional microporous metal-organic framework Zn(BDC)(Dabco)0.5 (BDC =
      1,4-benzenedicarboxylate, Dabco = 1,4-diazabicyclo [2,2,2]octane), having two
      types of intersecting pores to encapsulate linear hexane and to block branched
      hexanes, and thus exhibiting highly selective sorption with respect to n-hexane,
      has been successfully applied to the kinetic separation of hexane isomers by
      fixed-bed adsorption.

PMID- 17500559
TI  - A general and efficient five-step one-pot procedure leading to nitrogen
      bridgehead heterocycles containing an imidazole ring.
AB  - A very simple annulation reaction was designed, allowing an imidazole moiety to
      be fused onto a range of pyridine-based derivatives. The methodology consists of
      an activation step via the formation of a pyridinium salt to increase the
      electrophilicity of the pyridine ring, followed by a cascade reaction triggered
      by a nucleophilic attack of the iminium moiety. Depending on the pyridinium salt,
      it is possible to obtain functionalized imidazole moieties.

PMID- 17500560
TI  - Siloxanes with pendent naphthalene diimides: synthesis and fluorescence
      quenching.
AB  - Cyclic siloxanes with pendent naphthalene diimide groups were synthesized via
      hydrosilylation to form amorphous electron-accepting compounds. Photophysical
      measurements and >99.9% fluorescence quenching of well-known p-type polymers by
      the siloxanes demonstrate that these siloxanes form a new class of highly
      efficient n-type materials that provide some control over intermolecular
      interactions.

PMID- 17500561
TI  - Ionic transformations in extremely nonpolar fluorous media: phase transfer
      catalysis of halide substitution reactions.
AB  - Fluorous solutions of alkyl halides Rf8(CH2)mX (m = 2, 3; X = Cl, Br, I) are
      inert toward solid or aqueous NaCl, NaBr, and KI, but halide substitution occurs
      in the presence of fluorous phosphonium salts (10 mol %, 76-100 degrees C).

PMID- 17500562
TI  - Reconfigurable four-component molecular switch based on pH-controlled guest
      swapping.
AB  - The four-component ensemble comprising CB[6], beta-CD, and guests 1 and 2 forms
      complexes CB[6].1H+ and beta-CD.2 at pH < 7 but swaps partners forming complexes
      CB[6].2 and beta-CD.1 at pH > 13. The intermolecular nature of the switching
      process suggests application as a basis for stimuli-responsive reconfigurable
      systems.

PMID- 17500563
TI  - Cocrystal design gone awry? A new dimorphic hydrate of oxalic acid.
AB  - The crystal chemistry of oxalic acid has been studied since 1880, including 37
      published structure determinations of the two anhydrous forms (alpha, beta) and
      the dihydrate, the latest in 2000. In attempts to cocrystallize asparagine or
      glutamine with oxalic acid, utilizing the particular hydrogen bond synthon
      R(4)(2)(8), we unexpectedly obtained two previously unreported sesquihydrates of
      oxalic acid. Form 1 is orthorhombic, Pnma, and the unit cell is a = 11.231(2) A,
      b = 12.330(2) A, c = 6.908(1) A. Form 2 crystallizes in the triclinic crystal
      system in space group P, and the unit cell is a = 6.337(2) A; b = 7.247(3) A, c =
      10.571(4)A, alpha = 94.34(1) degrees, beta = 100.244(9) degrees, gamma = 97.67(1)
      degrees. Both of the new hydrate forms of oxalic acid utilized the R(4)(2)(8)
      hydrogen bonded synthon.

PMID- 17500564
TI  - Hierarchy of supramolecular synthons: persistent hydroxyl...pyridine hydrogen
      bonds in cocrystals that contain a cyano acceptor.
AB  - An analysis of the Cambridge Structural Database reveals >99% occurrence of the
      hydroxyl...pyridine supramolecular heterosynthon in crystal structures that
      contain hydroxyl and pyridine moieties in the absence of other hydrogen-bonding
      moieties. The occurrence of the hydroxyl...cyano supramolecular heterosynthon in
      crystal structures that contain hydroxyl and cyano moieties is ca. 77%. Such high
      frequencies indicate that these heterosynthons are strongly favored over the
      competing hydroxyl...hydroxyl supramolecular homosynthon. However, the CSD does
      not contain enough information to evaluate which supramolecular heterosynthon
      prevails when only OH, pyridine, and CN moieties are present in a crystal
      structure. We have addressed the competition between the hydroxyl...pyridine and
      the hydroxyl...cyano supramolecular heterosynthons by characterizing a series of
      17 cocrystals that are composed of cocrystal formers which contain a permutation
      of OH, pyridine, and CN functional groups. Structural analysis reveals that all
      cocrystals are sustained by the hydroxyl...pyridine heterosynthon.

PMID- 17500565
TI  - Structure of a 4:1:4 supramolecular assembly of neutral TiiiiPO cavitands and
      tetrakis(N-methylpyridinium)porphyrin iodide.
AB  - Four tetraphosphorylated TiiiiPO cavitands 1 encapsulate the pyridinium heads of
      a tetrakis(N-methylpyridinium)porphyrin iodide to form a 4:1:4 (host)4/guest4+/4I
      complex. The single-crystal X-ray diffraction analysis shows the arrangement of
      the four cavities bound to the CH3N+ groups of the porphyrin moiety and the four
      iodide anions nested between the phenethyl substituents of the hosts. 1H NMR
      investigations show that the structure is preserved in chloroform solution and
      underscore the effect of the counteranions.

PMID- 17500566
TI  - Pybox monolithic miniflow reactors for continuous asymmetric cyclopropanation
      reaction under conventional and supercritical conditions.
AB  - Supported catalysts having pybox chiral moieties were prepared as macroporous
      monolithic miniflow systems. These catalysts are based on styrene-divinylbenzene
      polymeric backbones having different compositions and pybox chiral moieties.
      Their corresponding ruthenium complexes were tested for the continuous flow
      cyclopropanation reaction between styrene and ethyldiazoacetate (EDA) under
      conventional conditions and in supercritical carbon dioxide (scCO2). Ru-Pybox
      monolithic miniflow reactors not only provided a highly efficient and robust
      heterogeneous chiral catalyst but also allowed us to develop more environmental
      reaction conditions without sacrificing the global efficiency of the process.

PMID- 17500567
TI  - A general and efficient 2-amination of pyridines and quinolines.
AB  - Pyridine N-oxides were converted to 2-aminopyridines in a one-pot fashion using
      Ts2O-t-BuNH2 followed by in situ deprotection with TFA. The amination proceeded
      in high yields, excellent 2-/4-selectivity, and with good functional group
      compatibility. 2-Amino (iso)quinolines were also obtained in the same manner.
      Combined with the simple oxidation of pyridines to pyridine N-oxides, this method
      provides a general and efficient way for amination of 2-unsubstituted pyridines.

PMID- 17500568
TI  - The first sequential reaction promoted by manganese: complete stereoselective
      synthesis of (E)-alpha,beta-unsaturated esters from 2,2-dichloroesters and
      aldehydes.
AB  - Alpha,beta-unsaturated esters were obtained with complete control of
      stereoselectivity utilizing a sequential reaction of dichloroesters with a
      variety of aldehydes, promoted by active manganese. This methodology is generally
      applicable, and the C-C double bond can be di- or trisubstituted. A mechanism
      based on a successive aldol-type reaction/beta-elimination is proposed to explain
      these results.

PMID- 17500569
TI  - Kinetics of the deprotonation of methylnitroacetate by amines: unusually high
      intrinsic rate constants for a nitroalkane.
AB  - A kinetic study of the reversible deprotonation of methylnitroacetate (4H) by
      primary aliphatic amines, secondary alicyclic amines, hydroxide ion, and water in
      water at 25 degrees C and in 50% DMSO/50% water (v/v) at 20 degrees C is
      reported. Intrinsic rate constants, k0, determined by extrapolation or
      interpolation of Bronsted plots have been determined. In comparison to proton
      transfers involving other nitroalkanes, the intrinsic rate constants for 4H are
      exceptionally high; for example, log k0 for the reaction of 4H with secondary
      alicyclic amines in water (1.22) is 1.81 log units higher than log k0 for
      nitromethane (-0.59), while in 50% DMSO/50% water, log k0 for 4H (2.44) is 1.71
      log units higher than that for nitromethane (0.73). A general discussion of the
      factors affecting intrinsic rate constants of proton transfer from nitroalkanes
      is presented; it provides the context for an understanding as to why k0 is so
      high for the proton transfers from 4H. The correlation between intrinsic rate
      constants for the addition of nucleophiles to alkenes of the type R'R' 'C=CXY and
      the intrinsic rate constants of proton transfers from carbon acids of the type
      H2CXY is also discussed as a general proposition as well as with specific
      reference to the Ph(SMe)C=C(NO2)CO2Me/H2C(NO2)CO2Me pair.

PMID- 17500570
TI  - Iriomoteolide-1a, a potent cytotoxic 20-membered macrolide from a benthic
      dinoflagellate amphidinium species.
AB  - A potent cytotoxic 20-membered macrolide, iriomoteolide-1a (1), has been isolated
      from a benthic dinoflagellate Amphidinium sp. (strain HYA024), and the structure
      was elucidated on the basis of detailed analyses of 2-D NMR data. The relative
      and absolute stereochemistries were assigned by the combination of conformational
      analyses using NMR data and modified Mosher's method of 1.

PMID- 17500572
TI  - Unusual naphthoquinone derivatives from the twigs of Avicennia marina.
AB  - In a continuing search for novel bioactive compounds from marine mangrove plants,
      seven new naphthoquinone derivatives were isolated from Avicennia marina, namely,
      avicennone A (1), avicennone B (2), avicennone C (3), avicennone D (4), avicenone
      E (5), avicennone F (6), and avicennone G (7), along with the known compounds
      avicequinone A (8), stenocarpoquinone B (9), avicequinone C (10), avicenol A
      (11), and avicenol C (12). The chemical structures of 1-7 were elucidated by
      spectroscopic methods. Compounds 8-10, and a mixture of 4 and 5, which all
      contain a 4,9-dione group, showed strong antiproliferative and moderate cytotoxic
      activities, as well as antibacterial effects.

PMID- 17500573
TI  - Spatially resolved product formation in the reaction of formic acid with calcium
      carbonate (1014): the role of step density and adsorbed water-assisted ion
      mobility.
AB  - The reaction of calcium carbonate (1014) single-crystal surfaces with formic acid
      (HCOOH) vapor was investigated using atomic force microscopy (AFM) and X-ray
      photoelectron spectroscopy (XPS). AFM images indicate the reaction produces
      rather well-defined crystallites, preferentially at step edges and at distinct
      angles to one another and mirroring the rhombohedral structure of the calcite
      surface, while exposing unreacted carbonate surface. The size and surface density
      of the crystallites depend upon substrate step density, exposure time, and
      relative humidity. XPS data confirmed the crystallite composition as the expected
      calcium formate product. The AFM images show erosion and pit formation of the
      calcite surface in the vicinity of the product crystallites, clearly providing
      the spatially resolved characterization of the source of Ca ions. AFM experiments
      exploring the effects of water vapor on the reacted surface show that the calcium
      formate crystallites are mobile under conditions of high relative humidity,
      combining to form larger crystallites and nanometer-sized crystals with an
      orthorhombohedral habit consistent with the alpha form, as confirmed by X-ray
      diffraction. The implications for the reactions described here are discussed.

PMID- 17500574
TI  - Production of complex cerium-aluminum oxides using an atmospheric pressure plasma
      torch.
AB  - Ceria-alumina particles of a wide variety of structures, from micrometer-sized
      hollow spheres to nanoparticles, were produced from aerosols of different
      natures, but all derived from nitrate salts passed through a low power (<1000 W)
      atmospheric pressure plasma torch. The amount of water present with the nitrate
      salts was found to significantly affect the morphology of the resulting material.
      A model was proposed that explains the mechanism in which water acts as a blowing
      agent to create hollow metal oxide spheres that then shatter to form metal oxide
      nanoparticles. Further examination of the nanoparticles revealed that they
      display a core/shell morphology in which the core material is crystalline CeO2
      and the shell material is amorphous Al2O3. These unique core/shell materials are
      interesting candidates for catalyst support materials with high thermal
      durability. In addition, experiments have shown that the nanoparticles can be
      readily converted into CeAlO3 perovskite.

PMID- 17500575
TI  - Plasma-mediated grafting of poly(ethylene glycol) on polyamide and polyester
      surfaces and evaluation of antifouling ability of modified substrates.
AB  - A simple cold plasma technique was developed to functionalize the surfaces of
      polyamide (PA) and polyester (PET) for the grafting of polyethylene glycol (PEG)
      with the aim of reducing biofilm formation. The surfaces of PA and PET were
      treated with silicon tetrachloride (SiCl4) plasma, and PEG was grafted onto
      plasma-functionalized substrates (PA-PEG, PET-PEG). Different molecular weights
      of PEG and grafting times were tested to obtain optimal surface coverage by PEG
      as monitored by electron spectroscopy for chemical analysis (ESCA). The presence
      of a predominant C-O peak on the PEG-modified substrates indicated that the
      grafting was successful. Data from hydroxyl group derivatization and water
      contact angle measurement also indicated the presence of PEG after grafting. The
      PEG-grafted PA and PET under optimal conditions had similar chemical composition
      and hydrophilicity; however, different morphology changes were observed after
      grafting. Both PA-PEG and PET-PEG surfaces developed under optimal plasma
      conditions showed about 96% reduction in biofilm formation by Listeria
      monocytogenes compared with that of the corresponding unmodified substrates. This
      plasma functionalization method provided an efficient way to graft PEG onto PA
      and PET surfaces. Because of the high reactivity of Si-Cl species, this method
      could potentially be applied to other polymeric materials.

PMID- 17500576
TI  - Frequency response of a quartz crystal microbalance loaded by liquid drops.
AB  - The frequency response of a quartz crystal microbalance (QCM) in contact with a
      spreading liquid drop is studied in this paper. An improved model describing the
      frequency change of the QCM with the shape evolution of the liquid drop with time
      is proposed based on hydrodynamic analysis, which has not been reported in the
      literature. It is found that the drop spreading shape, including the base radius
      and height, has a significant influence on the frequency response of the QCM,
      resulting in an unexpected increase in the resonant frequency of the QCM. The
      model shows that the combination of the knowledge about the radial sensitivity of
      the QCM and the dynamic spreading of the liquid drop is potentially important to
      optimize the interpretation of the experimental results. The predicted results
      are verified with experimental results obtained with silicone oil.

PMID- 17500577
TI  - Near-field evidence for ferromagnetic "nanoneedles" in Nd1/2Sr1/2MnO3.
AB  - We report on the near-field optical microscopic (NSOM) imaging of single-crystal
      Nd1/2Sr1/2MnO3 near the first-order phase transition from the CE-type charge
      ordered insulator (COI) to the ferromagnetic metal (FMM) at 165 K. Using
      polarized light, the measurements are sensitive to twin domains through optical
      anisotropy and to hysteretic inhomogeneous strain associated with the phase
      transition. Optical evidence for strain relaxation and multiphase coexistence is
      observed through the transition from 150 to 165 K. The multiphase coexistence is
      seen as the formation of FMM "nanoneedles" with widths less than 100 nm and
      lengths of at least several micrometers at temperatures well below TC. The work
      demonstrates polarized NSOM as a technique for the study of first-order solid
      state phase transformations on the nanometer spatial scale.

PMID- 17500578
TI  - Detecting SNPs using a synthetic nanopore.
AB  - We have discovered a voltage threshold for permeation through a synthetic
      nanopore of dsDNA bound to a restriction enzyme that depends on the sequence.
      Molecular dynamic simulations reveal that the threshold is associated with a
      nanonewton force required to rupture the DNA-protein complex. A single mutation
      in the recognition site for the restriction enzyme, i.e., a single nucleotide
      polymorphism (SNP), can easily be detected as a change in the threshold voltage.
      Consequently, by measuring the threshold voltage in a synthetic nanopore, it may
      be possible to discriminate between two variants of the same gene (alleles) that
      differ in one base.

PMID- 17500579
TI  - Plasmonic crystal demultiplexer and multiports.
AB  - We report the realization of two-dimensional optical wavelength demultiplexers
      and multiports for surface plasmons polaritons (SPPs) based on plasmonic
      crystals, i.e., photonic crystals for SPPs. These SPP elements are built up of
      lithographically fabricated gold nanostructures on gold thin films. We show by
      direct imaging of laterally confined SPP beams in the visible spectral range by
      leakage radiation microscopy that SPPs of different wavelengths are efficiently
      rerouted into different directions. In addition we demonstrate the generation of
      three output SPP beams from one input beam.

PMID- 17500580
TI  - Six-helix and eight-helix DNA nanotubes assembled from half-tubes.
AB  - DNA nanotubes are cylinder-like structures formed from DNA double-helical
      molecules whose helix axes are fused at least twice by crossovers. It is
      potentially useful to use such tubes as sheaths around rodlike species that arise
      in biological systems and in nanotechnology. It seems easiest to obtain such
      sheathing by joining two or more components around an object rather than
      attempting to thread the object through a cavity in the tube. We report two
      examples of tubes containing a specific number of helices that are assembled from
      half-tube components. These tubes are a six-helix bundle and an eight-helix
      bundle, constructed respectively from two bent triple-crossover (BTX) molecules
      and from two four-helix arched motifs. Both species contain single strands in one
      molecule that are missing in its mate. The six-helix bundle is formed from two
      different BTX molecules, whereas the eight-helix species is a closed cyclic dimer
      of the same molecule. We demonstrate the formation of these species by gel
      electrophoresis, and we examine their arrangement into long one-dimensional
      arrays by means of atomic force microscopy.

PMID- 17500582
TI  - Dielectrophoretic detection of membrane morphology changes in Jurkat T-cells
      undergoing etoposide-induced apoptosis.
AB  - A dielectrophoresis (DEP) cell profiler, with concurrent FACS measurements, was
      used to monitor the morphological changes of Jurkat T-cells as they progressed
      through chemically induced apoptosis using etoposide. The cell 'physiometry'
      profiling technique measures the radius and the so-called DEP crossover frequency
      f(xo) of individual cells in a suspension, and this information was used to
      determine the effective plasma membrane capacitance of each cell. Control cells
      (n=526) exhibited a dynamic spread of f(xo) values, ranging from 50 to 250 kHz,
      and as apoptosis progressed over 6 h, the upper value for f(xo) progressively
      increased and extended beyond 500 kHz. This corresponded to a reduction in plasma
      membrane capacitance from 13.34 (+/-2.88) to 10.49 (+/-4.00) mF/m(2), and
      reflected a general smoothing of the membrane through loss of microvilli, for
      example. This is in broad agreement with previously reported studies of HL-60
      cells undergoing apoptosis, but the authors' observation of a dynamic spread of
      f(xo) values does not agree with the earlier report that the f(xo) values for
      viable and apoptotic cells fall into two separable, relatively narrow, frequency
      bands. This has implications when devising protocols for the efficient DEP
      separation of viable, apoptotic and necrotic cells.

PMID- 17500583
TI  - Oxygen adsorption by carbon nanotubes and its application in radiotherapy.
AB  - The ability to deliver large molecules, for example nucleic acids, to cells using
      carbon nanotubes has been reviewed. Potential applications of functionalised
      nanotubes to deliver oxygen to cancer cells to enhance the effects of
      radiotherapy are considered.

PMID- 17500584
TI  - Integrated mechanisms of anticipation and rate-of-change computations in cortical
      circuits.
AB  - Local neocortical circuits are characterized by stereotypical physiological and
      structural features that subserve generic computational operations. These basic
      computations of the cortical microcircuit emerge through the interplay of
      neuronal connectivity, cellular intrinsic properties, and synaptic plasticity
      dynamics. How these interacting mechanisms generate specific computational
      operations in the cortical circuit remains largely unknown. Here, we identify the
      neurophysiological basis of both the rate of change and anticipation computations
      on synaptic inputs in a cortical circuit. Through biophysically realistic
      computer simulations and neuronal recordings, we show that the rate-of-change
      computation is operated robustly in cortical networks through the combination of
      two ubiquitous brain mechanisms: short-term synaptic depression and spike
      frequency adaptation. We then show how this rate-of-change circuit can be
      embedded in a convergently connected network to anticipate temporally incoming
      synaptic inputs, in quantitative agreement with experimental findings on
      anticipatory responses to moving stimuli in the primary visual cortex. Given the
      robustness of the mechanism and the widespread nature of the physiological
      machinery involved, we suggest that rate-of-change computation and temporal
      anticipation are principal, hard-wired functions of neural information processing
      in the cortical microcircuit.

PMID- 17500585
TI  - Enhancer responses to similarly distributed antagonistic gradients in
      development.
AB  - Formation of spatial gene expression patterns in development depends on
      transcriptional responses mediated by gene control regions, enhancers. Here, we
      explore possible responses of enhancers to overlapping gradients of antagonistic
      transcriptional regulators in the Drosophila embryo. Using quantitative models
      based on enhancer structure, we demonstrate how a pair of antagonistic
      transcription factor gradients with similar or even identical spatial
      distributions can lead to the formation of distinct gene expression domains along
      the embryo axes. The described mechanisms are sufficient to explain the formation
      of the anterior and the posterior knirps expression, the posterior hunchback
      expression domain, and the lateral stripes of rhomboid expression and of other
      ventral neurogenic ectodermal genes. The considered principles of interaction
      between antagonistic gradients at the enhancer level can also be applied to
      diverse developmental processes, such as domain specification in imaginal discs,
      or even eyespot pattern formation in the butterfly wing.

PMID- 17500586
TI  - HIV-1 subtype B protease and reverse transcriptase amino acid covariation.
AB  - Despite the high degree of HIV-1 protease and reverse transcriptase (RT) mutation
      in the setting of antiretroviral therapy, the spectrum of possible virus variants
      appears to be limited by patterns of amino acid covariation. We analyzed patterns
      of amino acid covariation in protease and RT sequences from more than 7,000
      persons infected with HIV-1 subtype B viruses obtained from the Stanford HIV Drug
      Resistance Database (http://hivdb.stanford.edu). In addition, we examined the
      relationship between conditional probabilities associated with a pair of
      mutations and the order in which those mutations developed in viruses for which
      longitudinal sequence data were available. Patterns of RT covariation were
      dominated by the distinct clustering of Type I and Type II thymidine analog
      mutations and the Q151M-associated mutations. Patterns of protease covariation
      were dominated by the clustering of nelfinavir-associated mutations (D30N and
      N88D), two main groups of protease inhibitor (PI)-resistance mutations associated
      either with V82A or L90M, and a tight cluster of mutations associated with
      decreased susceptibility to amprenavir and the most recently approved PI
      darunavir. Different patterns of covariation were frequently observed for
      different mutations at the same position including the RT mutations T69D versus
      T69N, L74V versus L74I, V75I versus V75M, T215F versus T215Y, and K219Q/E versus
      K219N/R, and the protease mutations M46I versus M46L, I54V versus I54M/L, and
      N88D versus N88S. Sequence data from persons with correlated mutations in whom
      earlier sequences were available confirmed that the conditional probabilities
      associated with correlated mutation pairs could be used to predict the order in
      which the mutations were likely to have developed. Whereas accessory nucleoside
      RT inhibitor-resistance mutations nearly always follow primary nucleoside RT
      inhibitor-resistance mutations, accessory PI-resistance mutations often preceded
      primary PI-resistance mutations.

PMID- 17500587
TI  - Binding site graphs: a new graph theoretical framework for prediction of
      transcription factor binding sites.
AB  - Computational prediction of nucleotide binding specificity for transcription
      factors remains a fundamental and largely unsolved problem. Determination of
      binding positions is a prerequisite for research in gene regulation, a major
      mechanism controlling phenotypic diversity. Furthermore, an accurate
      determination of binding specificities from high-throughput data sources is
      necessary to realize the full potential of systems biology. Unfortunately,
      recently performed independent evaluation showed that more than half the
      predictions from most widely used algorithms are false. We introduce a graph
      theoretical framework to describe local sequence similarity as the pair-wise
      distances between nucleotides in promoter sequences, and hypothesize that densely
      connected subgraphs are indicative of transcription factor binding sites. Using a
      well-established sampling algorithm coupled with simple clustering and scoring
      schemes, we identify sets of closely related nucleotides and test those for known
      TF binding activity. Using an independent benchmark, we find our algorithm
      predicts yeast binding motifs considerably better than currently available
      techniques and without manual curation. Importantly, we reduce the number of
      false positive predictions in yeast to less than 30%. We also develop a framework
      to evaluate the statistical significance of our motif predictions. We show that
      our approach is robust to the choice of input promoters, and thus can be used in
      the context of predicting binding positions from noisy experimental data. We
      apply our method to identify binding sites using data from genome scale ChIP-chip
      experiments. Results from these experiments are publicly available at
      http://cagt10.bu.edu/BSG. The graphical framework developed here may be useful
      when combining predictions from numerous computational and experimental measures.
      Finally, we discuss how our algorithm can be used to improve the sensitivity of
      computational predictions of transcription factor binding specificities.

PMID- 17500588
TI  - A novel linear plasmid mediates flagellar variation in Salmonella Typhi.
AB  - Unlike the majority of Salmonella enterica serovars, Salmonella Typhi (S. Typhi),
      the etiological agent of human typhoid, is monophasic. S. Typhi normally harbours
      only the phase 1 flagellin gene (fliC), which encodes the H:d antigen. However,
      some S. Typhi strains found in Indonesia express an additional flagellin antigen
      termed H:z66. Molecular analysis of H:z66+ S. Typhi revealed that the H:z66
      flagellin structural gene (fljB(z66)) is encoded on a linear plasmid that we have
      named pBSSB1. The DNA sequence of pBSSB1 was determined to be just over 27 kbp,
      and was predicted to encode 33 coding sequences. To our knowledge, pBSSB1 is the
      first non-bacteriophage-related linear plasmid to be described in the
      Enterobacteriaceae.

PMID- 17500589
TI  - Spatial, temporal, and species variation in prevalence of influenza A viruses in
      wild migratory birds.
AB  - Although extensive data exist on avian influenza in wild birds in North America,
      limited information is available from elsewhere, including Europe. Here,
      molecular diagnostic tools were employed for high-throughput surveillance of
      migratory birds, as an alternative to classical labor-intensive methods of virus
      isolation in eggs. This study included 36,809 samples from 323 bird species
      belonging to 18 orders, of which only 25 species of three orders were positive
      for influenza A virus. Information on species, locations, and timing is provided
      for all samples tested. Seven previously unknown host species for avian influenza
      virus were identified: barnacle goose, bean goose, brent goose, pink-footed
      goose, bewick's swan, common gull, and guillemot. Dabbling ducks were more
      frequently infected than other ducks and Anseriformes; this distinction was
      probably related to bird behavior rather than population sizes. Waders did not
      appear to play a role in the epidemiology of avian influenza in Europe, in
      contrast to the Americas. The high virus prevalence in ducks in Europe in spring
      as compared with North America could explain the differences in virus-host
      ecology between these continents. Most influenza A virus subtypes were detected
      in ducks, but H13 and H16 subtypes were detected primarily in gulls. Viruses of
      subtype H6 were more promiscuous in host range than other subtypes. Temporal and
      spatial variation in influenza virus prevalence in wild birds was observed, with
      influenza A virus prevalence varying by sampling location; this is probably
      related to migration patterns from northeast to southwest and a higher prevalence
      farther north along the flyways. We discuss the ecology and epidemiology of avian
      influenza A virus in wild birds in relation to host ecology and compare our
      results with published studies. These data are useful for designing new
      surveillance programs and are particularly relevant due to increased interest in
      avian influenza in wild birds.

PMID- 17500590
TI  - Identification of cellular genes targeted by KSHV-encoded microRNAs.
AB  - MicroRNAs (miRNAs) are 19 to 23 nucleotide-long RNAs that post-transcriptionally
      regulate gene expression. Human cells express several hundred miRNAs which
      regulate important biological pathways such as development, proliferation, and
      apoptosis. Recently, 12 miRNA genes have been identified within the genome of
      Kaposi sarcoma-associated herpesvirus; however, their functions are still
      unknown. To identify host cellular genes that may be targeted by these novel
      viral regulators, we performed gene expression profiling in cells stably
      expressing KSHV-encoded miRNAs. Data analysis revealed a set of 81 genes whose
      expression was significantly changed in the presence of miRNAs. While the
      majority of changes were below 2-fold, eight genes were down-regulated between 4-
      and 20-fold. We confirmed miRNA-dependent regulation for three of these genes and
      found that protein levels of thrombospondin 1 (THBS1) were decreased >10-fold.
      THBS1 has previously been reported to be down-regulated in Kaposi sarcoma lesions
      and has known activity as a strong tumor suppressor and anti-angiogenic factor,
      exerting its anti-angiogenic effect in part by activating the latent form of TGF
      beta. We show that reduced THBS1 expression in the presence of viral miRNAs
      translates into decreased TGF-beta activity. These data suggest that KSHV-encoded
      miRNAs may contribute directly to pathogenesis by down-regulation of THBS1, a
      major regulator of cell adhesion, migration, and angiogenesis.

PMID- 17500591
TI  - Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania
      major infection.
AB  - Effector responses induced by polarized CD4+ T helper 2 (Th2) cells drive
      nonhealing responses in BALB/c mice infected with Leishmania major. Th2 cytokines
      IL-4 and IL-13 are known susceptibility factors for L. major infection in BALB/c
      mice and induce their biological functions through a common receptor, the IL-4
      receptor alpha chain (IL-4Ralpha). IL-4Ralpha-deficient BALB/c mice, however,
      remain susceptible to L. major infection, indicating that IL-4/IL-13 may induce
      protective responses. Therefore, the roles of polarized Th2 CD4+ T cells and IL
      4/IL-13 responsiveness of non-CD4+ T cells in inducing non-healer or healer
      responses have yet to be elucidated. CD4+ T cell-specific IL-4Ralpha (Lck(cre)IL
      4Ralpha(-/lox)) deficient BALB/c mice were generated and characterized to
      elucidate the importance of IL-4Ralpha signaling during cutaneous leishmaniasis
      in the absence of IL-4-responsive CD4+ T cells. Efficient deletion was confirmed
      by loss of IL-4Ralpha expression on CD4+ T cells and impaired IL-4-induced CD4+ T
      cell proliferation and Th2 differentiation. CD8+, gammadelta+, and NK-T cells
      expressed residual IL-4Ralpha, and representative non-T cell populations
      maintained IL-4/IL-13 responsiveness. In contrast to IL-4Ralpha(-/lox) BALB/c
      mice, which developed ulcerating lesions following infection with L. major,
      Lck(cre)IL-4Ralpha(-/lox) mice were resistant and showed protection to
      rechallenge, similar to healer C57BL/6 mice. Resistance to L. major in Lck(cre)IL
      4Ralpha(-/lox) mice correlated with reduced numbers of IL-10-secreting cells and
      early IL-12p35 mRNA induction, leading to increased delayed type hypersensitivity
      responses, interferon-gamma production, and elevated ratios of inducible nitric
      oxide synthase mRNA/parasite, similar to C57BL/6 mice. These data demonstrate
      that abrogation of IL-4 signaling in CD4+ T cells is required to transform non
      healer BALB/c mice to a healer phenotype. Furthermore, a beneficial role for IL
      4Ralpha signaling in L. major infection is revealed in which IL-4/IL-13
      responsive non-CD4+ T cells induce protective responses.

PMID- 17500592
TI  - Rapid birth-death evolution specific to xenobiotic cytochrome P450 genes in
      vertebrates.
AB  - Genes vary greatly in their long-term phylogenetic stability and there exists no
      general explanation for these differences. The cytochrome P450 (CYP450) gene
      superfamily is well suited to investigating this problem because it is large and
      well studied, and it includes both stable and unstable genes. CYP450 genes encode
      oxidase enzymes that function in metabolism of endogenous small molecules and in
      detoxification of xenobiotic compounds. Both types of enzymes have been
      intensively studied. My analysis of ten nearly complete vertebrate genomes
      indicates that each genome contains 50-80 CYP450 genes, which are about evenly
      divided between phylogenetically stable and unstable genes. The stable genes are
      characterized by few or no gene duplications or losses in species ranging from
      bony fish to mammals, whereas unstable genes are characterized by frequent gene
      duplications and losses (birth-death evolution) even among closely related
      species. All of the CYP450 genes that encode enzymes with known endogenous
      substrates are phylogenetically stable. In contrast, most of the unstable genes
      encode enzymes that function as xenobiotic detoxifiers. Nearly all unstable
      CYP450 genes in the mouse and human genomes reside in a few dense gene clusters,
      forming unstable gene islands that arose by recurrent local gene duplication.
      Evidence for positive selection in amino acid sequence is restricted to these
      unstable CYP450 genes, and sites of selection are associated with substrate
      binding regions in the protein structure. These results can be explained by a
      general model in which phylogenetically stable genes have core functions in
      development and physiology, whereas unstable genes have accessory functions
      associated with unstable environmental interactions such as toxin and pathogen
      exposure. Unstable gene islands in vertebrates share some functional properties
      with bacterial genomic islands, though they arise by local gene duplication
      rather than horizontal gene transfer.

PMID- 17500593
TI  - Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27
      control visceral leishmaniasis in Sudan.
AB  - Familial clustering and ethnic differences suggest that visceral leishmaniasis
      caused by Leishmania donovani is under genetic control. A recent genome scan
      provided evidence for a major susceptibility gene on Chromosome 22q12 in the
      Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families
      with 173 affected relatives from two villages occupied by the related Masalit
      ethnic group. A primary ten-centimorgan scan followed by refined mapping provided
      evidence for major loci at 1p22 (LOD score 5.65; nominal p = 1.72 x 10(-7);
      empirical p < 1 x 10(-5); lambdaS = 5.1) and 6q27 (LOD score 3.74; nominal p =
      1.68 x 10(-5); empirical p < 1 x 10(-4); lambdaS = 2.3) that were Y chromosome
      lineage and village-specific. Neither village supported a visceral leishmaniasis
      susceptibility gene on 22q12. The results suggest strong lineage-specific genes
      due to founder effect and consanguinity in these recently immigrant populations.
      These chance events in ethnically uniform African populations provide a powerful
      resource in the search for genes and mechanisms that regulate this complex
      disease.

PMID- 17500594
TI  - Drosophila SETDB1 is required for chromosome 4 silencing.
AB  - Histone H3 lysine 9 (H3K9) methylation is associated with gene repression and
      heterochromatin formation. In Drosophila, SU(VAR)3-9 is responsible for H3K9
      methylation mainly at pericentric heterochromatin. However, the histone
      methyltransferases responsible for H3K9 methylation at euchromatic sites,
      telomeres, and at the peculiar Chromosome 4 have not yet been identified. Here,
      we show that DmSETDB1 is involved in nonpericentric H3K9 methylation. Analysis of
      two DmSetdb1 alleles generated by homologous recombination, a deletion, and an
      allele where the 3HA tag is fused to the endogenous DmSetdb1, reveals that this
      gene is essential for fly viability and that DmSETDB1 localizes mainly at
      Chromosome 4. It also shows that DmSETDB1 is responsible for some of the H3K9
      mono- and dimethyl marks in euchromatin and for H3K9 dimethylation on Chromosome
      4. Moreover, DmSETDB1 is required for variegated repression of transgenes
      inserted on Chromosome 4. This study defines DmSETDB1 as a H3K9 methyltransferase
      that specifically targets euchromatin and the autosomal Chromosome 4 and shows
      that it is an essential factor for Chromosome 4 silencing.

PMID- 17500596
TI  - Ten simple rules for making good oral presentations.

PMID- 17500595
TI  - Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
AB  - Huntington's disease (HD) is a fatal neurodegenerative condition caused by
      expansion of the polyglutamine tract in the huntingtin (Htt) protein. Neuronal
      toxicity in HD is thought to be, at least in part, a consequence of protein
      interactions involving mutant Htt. We therefore hypothesized that genetic
      modifiers of HD neurodegeneration should be enriched among Htt protein
      interactors. To test this idea, we identified a comprehensive set of Htt
      interactors using two complementary approaches: high-throughput yeast two-hybrid
      screening and affinity pull down followed by mass spectrometry. This effort led
      to the identification of 234 high-confidence Htt-associated proteins, 104 of
      which were found with the yeast method and 130 with the pull downs. We then
      tested an arbitrary set of 60 genes encoding interacting proteins for their
      ability to behave as genetic modifiers of neurodegeneration in a Drosophila model
      of HD. This high-content validation assay showed that 27 of 60 orthologs tested
      were high-confidence genetic modifiers, as modification was observed with more
      than one allele. The 45% hit rate for genetic modifiers seen among the
      interactors is an order of magnitude higher than the 1%-4% typically observed in
      unbiased genetic screens. Genetic modifiers were similarly represented among
      proteins discovered using yeast two-hybrid and pull-down/mass spectrometry
      methods, supporting the notion that these complementary technologies are equally
      useful in identifying biologically relevant proteins. Interacting proteins
      confirmed as modifiers of the neurodegeneration phenotype represent a diverse
      array of biological functions, including synaptic transmission, cytoskeletal
      organization, signal transduction, and transcription. Among the modifiers were 17
      loss-of-function suppressors of neurodegeneration, which can be considered
      potential targets for therapeutic intervention. Finally, we show that seven
      interacting proteins from among 11 tested were able to co-immunoprecipitate with
      full-length Htt from mouse brain. These studies demonstrate that high-throughput
      screening for protein interactions combined with genetic validation in a model
      organism is a powerful approach for identifying novel candidate modifiers of
      polyglutamine toxicity.

PMID- 17500597
TI  - Cultural pluralism and prejudice reduction.
AB  - Predictions derived from models of cultural pluralism and cultural assimilation
      were tested. Previous research has shown that highlighting differences between
      ethnic groups, in conjunction with self-focus, can reduce prejudice. The
      presented research tested the following questions: (a) does highlighting
      differences function to reduce prejudice between groups that are dissimilar to
      each other as well as between those that are highly similar, (b) is prejudice
      reduction due to distinctiveness a function of the lessened ingroup positivity or
      lessened outgroup negativity, (c) does making distinctiveness salient reduce
      prejudice toward only the distinctive outgroups or to outgroups more generically,
      and (d) does the manipulation equally impact African American, Mexican American,
      Mexican National, and White American participants? Results demonstrated that
      highlighting differences while simultaneously focusing on the self reduces
      prejudice, although similarity mediates the relationship with those who are
      perceived as more different. Distinctiveness also reduced outgroup negativity and
      generalized to other outgroups. Finally, the manipulation reduced prejudice only
      for White Americans, Mexican Americans, and Mexican Nationals.

PMID- 17500598
TI  - The color and texture of hope: some preliminary findings and implications for
      hope theory and counseling among diverse racial/ethnic groups.
AB  - To clarify and extend Snyder's (1994, 2002) hope theory to a more diverse
      population, this study examined variations in agentic and pathways thinking, and
      their relations with social problem solving, affect, and with life satisfaction
      across a college student sample of 46 European Americans, 30 African Americans,
      33 Latinos, and 46 Asian Americans. Although comparative results indicated
      variations in levels of hope components across the 4 racial/ethnic groups,
      correlational results indicated that the manner in which hope components related
      to measures of behavior and adjustment were similar across groups. Regression
      results indicated similarities and differences in predictors of hope components
      across the different racial/ethnic groups. Potential implications for promoting
      hope in working with diverse college students are discussed.

PMID- 17500599
TI  - The relationship between campus diversity, students' ethnic identity and college
      adjustment: a qualitative study.
AB  - The present study was a qualitative exploration into the meaning of ethnic
      identity and its association with college adjustment in students attending
      ethnically diverse university campuses. The sample consisted of 103 participants
      recruited from 2 ethnically diverse universities in southern California. A
      constant comparative analysis of the interview data revealed 9 themes as being
      relevant to students' experiences of ethnicity within a multiethnic campus that
      reflect both the positive aspects and the negative aspects associated with campus
      diversity. Students' experiences with campus diversity varied by ethnic
      background and type of institution attended, as did the overall frequencies of
      reported positive and negative themes associated with diversity. The implications
      of these findings for ethnic identity, campus climate, and interethnic relations
      are discussed.

PMID- 17500600
TI  - The psychology of diaspora experiences: intergroup contact, perceived
      discrimination, and the ethnic identity of Koreans in China.
AB  - The moderating role of intergroup contact on the relationship between perceived
      discrimination and ethnic identity was examined in a diaspora community of
      Koreans living in China. It was hypothesized that Koreans with higher intergroup
      contact would have a lower ethnic identity under higher discrimination, whereas
      Koreans with lower intergroup contact would have a higher ethnic identity. Across
      two separate college samples, Koreans who were more willing to interact with Han
      Chinese had a lower ethnic identity when discrimination was higher, but this
      finding was not replicated within one college setting. These findings challenge
      the linear rejection-identification model and suggest displaced people may
      minimize ingroup-outgroup differences, depending on their willingness to seek
      intergroup contact.

PMID- 17500601
TI  - The social construction of race: biracial identity and vulnerability to
      stereotypes.
AB  - Multiracial individuals are more likely to have a heightened awareness of race as
      a social construct than monoracial individuals. This article examines the impact
      that a heightened awareness of race as a social construct has on the relationship
      between racial stereotypes and performance. Study 1 finds that multiracial
      individuals reported subscribing less to the notion that race biologically
      determines ability. Study 2 finds that monoracial individuals show stereotype
      activation, whereas multiracial individuals show stereotype inhibition in
      reaction to race salience. Study 3 draws on the work on stereotypes and
      performance to test the susceptibility of multiracial individuals to racial
      stereotypes about ability. The authors find that Asian/White and Black/White
      multiracial individuals were less susceptible to racial stereotypes than
      monoracial individuals. Whereas monoracial participants showed significant
      performance changes in reaction to race salience, multiracial individuals did
      not. Study 4 finds that emphasizing the social construction of race buffers
      individuals from stereotype threat effects.

PMID- 17500602
TI  - Self-construal, mental distress, and family relations: a mediated moderation
      analysis with Asian American adolescents.
AB  - The interactive effects between interdependent and independent self-construal on
      family cohesion and mental distress were examined. Survey responses from 153
      Asian American high school students supported the hypothesized moderation of
      interdependence by independence on family cohesion, which was found to further
      mediate the relationship between self-construal and mental distress.
      Specifically, interdependence was positively associated with family cohesion when
      independence was high and negatively associated with family cohesion when
      independence was low. Accounting for the mediator effects of family cohesion,
      mental distress was positively associated with interdependence and more so for
      those low on independence than those high on independence. The benefits of
      biculturalism and research implications for the bidimensional conceptualization
      of self-construal for ethnic minority populations are discussed.

PMID- 17500603
TI  - Adolescent culture brokering and family functioning: a study of families from
      Vietnam.
AB  - In immigrant families, culture brokering (CB) refers to the ways in which
      children and adolescents serve as mediator between their family and aspects of
      the new culture. This study focused on the debate in the literature about whether
      CB implies "role reversal" in the family and "adultification" of the adolescent
      or whether CB is better understood as simply one of the many ways that immigrant
      children contribute to family functioning. Results indicated a mixed picture with
      respect to this debate. Greater amounts of adolescent CB were indeed related to
      higher adolescent reports of family conflict, but also to greater family
      adaptability. In addition, the amount of CB was unrelated to family satisfaction
      and family cohesion. Secondary questions centered on the relationship of CB to
      adolescent and parent demographic and acculturation variables. Here, CB was
      related to parent acculturation patterns but not those of adolescents.
      Implications for future research on the CB role are discussed.

PMID- 17500604
TI  - African American mother-daughter communication about sex and daughters' sexual
      behavior: does college racial composition make a difference?
AB  - This study examined the influence of African American mothers' communication
      about sexual topics on the sexual attitudes and behavior of their college
      enrolled daughters. Daughters were enrolled at a historically Black
      college/university (HBCU) or a predominantly White institution (PWI) to assess
      whether and how college racial context might affect daughters' sexual attitudes
      and behavior. Findings indicated that daughters at the HBCU had less permissive
      attitudes about premarital sex than their counterparts at the PWI. This result
      was especially true for daughters of mothers with more conservative attitudes
      about premarital sex and who discussed such topics infrequently. Last, the
      combination of positive mother-daughter communication and fewer discussions about
      sexual topics resulted in lower levels of sexual experience among the daughters.

PMID- 17500605
TI  - Psychometric analyses of the Clinician-Administered PTSD Scale (CAPS)--Bosnian
      translation.
AB  - Methods for assessing psychological distress in culturally diverse populations
      are not firmly established. This study was designed to examine the psychometric
      properties of the Bosnian translation of the Clinician-Administered PTSD Scale
      (CAPS; D. D. Blake, F. W. Weathers, L. M. Nagy, D. Kaloupek, G. Klauminzer, D.
      Charney, et al., 1995) in a Bosnian refugee sample. The authors interviewed 115
      help-seeking Bosnian refugees with the CAPS-Bosnian translation to examine its
      internal consistency and convergent validity, and to provide an assessment of its
      factor structure. This study demonstrated optimal fit with a 2-factor model of
      posttraumatic stress disorder (PTSD); the authors also found high reliability
      with a coefficient alpha of 0.92 and strong convergent validity with instruments
      measuring depression, anxiety, and levels of psychosocial functioning. Future
      directions for the assessment of PTSD in cross-cultural populations are
      discussed.

PMID- 17500606
TI  - Using mediators and moderators to test assumptions underlying culturally
      sensitive therapies: an exploratory example.
AB  - Factors hypothesized to impact Asian American responses to counseling were tested
      as mediators and moderators of perceived counselor credibility and working
      alliance. Asian and European American college students (N = 182) were assigned
      randomly to view simulated directive or nondirective therapy approaches.
      Mediation analyses examined whether ethnic group differences in initial
      perceptions were accounted for by therapist understandability and previous
      therapy experiences. Moderation analyses examined whether expectations for
      directive therapy, ambiguity tolerance, and resistance influenced initial
      perceptions across directive and nondirective counseling. Asian Americans rated
      the counseling approaches significantly less favorably than Europeans Americans.
      A significant mediation effect was found for therapist understandability, whereas
      a significant moderation effect was found for expectation for directive therapy
      on initial perceptions of counselor credibility.

PMID- 17500607
TI  - An examination of ethnic identity and self-esteem with diverse populations:
      exploring variation by ethnicity and geography.
AB  - The current study examined the relationships among ethnic identity and self
      esteem across multiple ethnic groups within two distinct geographical locations
      (N = 1,344). In the current study, for same ethnic group members, the components
      of ethnic identity (i.e., exploration, resolution, and affirmation) were
      differentially related to self-esteem based on geographical context. Furthermore,
      within each geographical context, the strength of the relation between each
      ethnic identity component and self-esteem varied based on group membership,
      suggesting that the variables may be more or less influential on self-esteem
      depending on one's group membership. Based on these results, the exploration and
      resolution subscales of the Ethnic Identity scale (EIS) appear to be valid and
      reliable with diverse samples, whereas support for the affirmation subscale of
      the EIS is more tenuous. Finally, these findings suggest that ethnic identity may
      have varying salience and meaning for same ethnic group members in different
      geographical contexts (e.g., Asian Americans in California vs. Asian Americans in
      the Midwest).

PMID- 17500608
TI  - The protective effects of ethnic identity for alcohol and marijuana use among
      Black young adults.
AB  - This study examined the extent to which individual differences in alcohol and
      marijuana use among 167 Black university students could be accounted for by
      degree of ethnic identity. After controlling for year in school, sex, and
      friends' substance use, higher levels of ethnic identity indeed were found to be
      significantly related to lower beer/hard liquor use, wine use, and marijuana use,
      accounting for approximately 31%, 6%, and 4% of the variance, respectively. For
      marijuana use, however, friends' substance use accounted for more of the variance
      (13%) than did ethnic identity (4%).

PMID- 17500610
TI  - Psychological interventions for arthritis pain management in adults: a meta
      analysis.
AB  - CONTEXT: The psychosocial impact of arthritis can be profound. There is growing
      interest in psychosocial interventions for managing pain and disability in
      arthritis patients. OBJECTIVE: This meta-analysis reports on the efficacy of
      psychosocial interventions for arthritis pain and disability. DATA SOURCES:
      Articles evaluating psychosocial interventions for arthritis were identified
      through Cochrane Controlled Trials, EMBASE, Ovid MEDLINE, and Ovid PsycINFO data
      sources. STUDY SELECTION: Randomized controlled trials testing the efficacy of
      psychosocial interventions in arthritis pain management were reviewed. DATA
      EXTRACTION: Twenty-seven randomized controlled trials were analyzed. Pain
      intensity was the primary outcome. Secondary outcomes included psychological,
      physical, and biological functioning. DATA SYNTHESIS: An overall effect size of
      0.177 (95% CI=0.256-0.094) indicated that patients receiving psychosocial
      interventions reported significantly lower pain than patients in control
      conditions (combined p=.01). Meta-analyses also supported the efficacy of
      psychosocial interventions for the secondary outcomes. CONCLUSIONS: These
      findings indicate that psychosocial interventions may have significant effects on
      pain and other outcomes in arthritis patients. Ample evidence for the additional
      benefit of such interventions over and above that of standard medical care was
      found.

PMID- 17500611
TI  - Predictors of calcium intake patterns: a longitudinal analysis.
AB  - OBJECTIVE: The study was guided by the precaution adoption process model; the
      author examined factors associated with (a) stage of change with respect to
      calcium intake at 4 time points and (b) calcium intake patterns across time.
      DESIGN: Data were collected by mailed questionnaire at baseline and at 3 follow
      up assessments over 1 year. MAIN OUTCOME MEASURES: The primary outcome measures
      were calcium intake, stage of change with respect to calcium intake, and pattern
      of calcium intake across follow-up. Three patterns were identified: successful
      maintenance (adequate calcium intake at all 3 follow-ups), vacillation (adequate
      calcium consumption at 1 or 2 follow-ups), and inertia (inadequate calcium
      consumption at all 3 follow-ups). RESULTS: Five hundred six women completed
      baseline questionnaires, and 346 completed 3 follow-up assessments. Even after
      baseline stage of change was controlled for, longitudinal analyses revealed 3
      variables that predicted different patterns of behavior across time. Isolated
      instances of adequate calcium intake were predicted by higher levels of knowledge
      and perceived benefits, whereas long-term maintenance was predicted by lower
      levels of perceived difficulty. CONCLUSION: These findings provide support for a
      central premise of the model, that different factors are important at different
      points in the behavior change process.

PMID- 17500612
TI  - Beyond cognition: predicting health risk behaviors from instrumental and
      affective beliefs.
AB  - OBJECTIVE: Two studies assessed the relative contribution of affective and
      instrumental beliefs to the prediction of 2 risk behaviors: driving above the
      speed limit and smoking. DESIGN: Both studies took the form of large-scale
      questionnaire surveys (Study 1, N=292; Study 2, N=500) measuring instrumental and
      affective beliefs and self-reported behavior. In both cases, behavior was also
      measured objectively. OUTCOME MEASURES: In Study 1, speeding behavior was
      measured via infrared camera along sections of road with 30 mph, 40 mph, and 60
      mph speed limits. Self-reports of speeding in these same contexts represented a
      2nd dependent variable. In Study 2, level of smoking was measured via a carbon
      monoxide monitor, and participants were asked to indicate the number of
      cigarettes they smoked in a week. RESULTS: In Study 1, positive and negative
      instrumental and affective beliefs were significant predictors of self-reported
      speed. The most powerful predictor was negative affective beliefs. Observed speed
      was predicted by negative affective beliefs only. In Study 2, the significant
      predictors of self-reported smoking and objective measures of smoking were
      positive and negative affective beliefs. CONCLUSION: The findings indicate the
      importance of affective beliefs across 2 health risk behaviors. Implications for
      social cognition models and interventions are discussed.

PMID- 17500613
TI  - Secondary smoking prevention in a university setting: a randomized comparison of
      an experiential, theory-based intervention and a standard didactic intervention
      for increasing cessation motivation.
AB  - OBJECTIVE: College may represent an untapped opportunity to reach the growing
      number of student smokers who are at risk of progressing toward regular smoking.
      The aim of this study was to test the efficacy of a theory-based experiential
      intervention for increasing motivation to quit smoking and reducing smoking
      behavior. DESIGN: This study used a 3-arm, randomized design to examine the
      efficacy of an experiential secondary prevention intervention. The control groups
      included a traditional didactic smoking intervention and an experiential
      intervention on nutrition. MAIN OUTCOME MEASURES: The 2 primary dependent
      variables were change in self-reported intention to quit smoking, measured pre-
      and postintervention, and change in smoking behavior over the month following the
      intervention. RESULTS: As hypothesized, the experiential smoking intervention was
      more effective than either control group in increasing immediate motivation to
      quit, but the effect was found only among female participants. At 1-month follow
      up, both smoking interventions produced higher rates of smoking cessation and
      reduction than did the nutrition control condition. CONCLUSION: Findings support
      the potential efficacy of an intensive experiential intervention for female
      smokers.

PMID- 17500614
TI  - Demographic variables, smoking variables, and outcome across five studies.
AB  - OBJECTIVE: Intervention effectiveness can potentially be affected by membership
      in different demographic subgroups (race, ethnicity, gender, age, and education
      level) or smoking behavior variables (time to first cigarette, longest previous
      quit attempt, number of attempts in the past year, number of cigarettes, and
      stage of change). Previous research on these 2 sets of variables has produced
      mixed results. DESIGN: This secondary data analysis combined data from 5
      effectiveness trials (a random-digit-dial sample [N=1,358], members of an HMO
      [N=207], parents of students recruited for a school-based study [N=347], patients
      from an insurance provider list [N=535], and employees [N=175]) in which smokers
      were all proactively recruited from a defined population and all received the
      same expert system intervention. The intervention produced a consistent 22% to
      26% point prevalence cessation rate across the 5 studies. MAIN OUTCOME MEASURES:
      The main outcome measures were 24-hr point prevalence, 7-day point prevalence, 30
      day prolonged abstinence, and 6-month prolonged abstinence. RESULTS: There were
      no significant differences in outcome across gender, race, and ethnicity
      subgroups. There were significant differences and small effect sizes for age and
      education subgroups. There were significant differences and large effect sizes
      for all 5 smoking behavior variables. DISCUSSION: Demographic variables are
      static variables, whereas the smoking variables are more dynamic, that is, open
      to change. Given the dynamic nature of the smoking variables and the large effect
      sizes, interventions tailored on the smoking variables should be more successful.

PMID- 17500615
TI  - Sleep and the affective response to stress and pain.
AB  - OBJECTIVE: The current study examined sleep disturbance (i.e., sleep duration,
      sleep quality) as a correlate of stress reactivity and pain reactivity. DESIGN
      AND OUTCOME MEASURES: An ecological momentary assessment design was used to
      evaluate the psychosocial functioning of men and women with fibromyalgia or
      rheumatoid arthritis (N=49). Participants recorded numeric ratings of pain, the
      occurrence of a stressful event, as well as positive and negative affect 7 times
      throughout the day for 2 consecutive days. In addition, participants reported on
      their sleep duration and sleep quality each morning. RESULTS: Sleep disruption
      was not found to be an independent predictor of affect. However, sleep was found
      to buffer the relationship between stress and negative affect and the
      relationship between pain and both positive and negative affect. CONCLUSION:
      These results are consistent with a model in which good-quality sleep acts as a
      biobehavioral resource that minimizes allostatic load.

PMID- 17500616
TI  - Blood lead (Pb) levels: a potential environmental mechanism explaining the
      relation between socioeconomic status and cardiovascular reactivity in children.
AB  - OBJECTIVE: A number of studies have shown an association between socioeconomic
      status (SES) and cardiovascular reactivity to acute stress. In addition, the
      authors recently reported that higher early childhood blood lead (Pb) levels are
      associated with significantly greater total peripheral (vascular) resistance
      (TPR) responses to acute stress. It is not known whether the SES-TPR association
      is mediated by underlying differences in blood lead levels. DESIGN: Participants
      were 9.5-year-old children (N=122) with established early childhood blood lead
      levels. MAIN OUTCOME MEASURES: Family SES was measured using the Hollingshead
      Index, blood lead levels were abstracted from pediatrician and state records, and
      children's cardiovascular responses to acute stressors were measured in the
      laboratory with impedance cardiography and an automated blood pressure monitor.
      RESULTS: Lower family SES was shown to be associated with significantly higher
      blood lead levels as well as significantly heightened systolic blood pressure,
      diastolic blood pressure, and TPR responses to acute stress tasks. A mediational
      analysis confirmed that Pb was a significant mediator of the SES-TPR reactivity
      association; some evidence also suggested moderation. CONCLUSION: These results
      suggest the importance of considering the chemical environment as well as social
      and psychological environment when evaluating cardiovascular effects of low SES.

PMID- 17500617
TI  - Plasma interleukin-6 and soluble IL-6 receptors are associated with psychological
      well-being in aging women.
AB  - OBJECTIVE: This study tested the hypothesis that psychological well-being would
      predict lower plasma levels of inflammatory factors in aging women. DESIGN: One
      hundred thirty-five women ages 61-91 years (M = 74.5 years) participated in this
      study. After completing self-administered questionnaires in their homes,
      participants stayed overnight at the General Clinical Research Center (GCRC) at
      the University of Wisconsin-Madison. Blood samples for cytokine analyses were
      obtained in participants' homes after the GCRC visit. MAIN OUTCOME MEASURES:
      Psychological well-being and ill-being, history of health problems, and health
      behaviors were assessed via self-administered questionnaires. Detailed medical
      history and concurrent health measures were obtained during the GCRC stay. Enzyme
      linked immunosorbent assays were used to determine interleukin-6 (IL-6) and
      soluble IL-6 receptor (sIL-6R) concentrations in plasma. RESULTS AND CONCLUSION:
      Regression analyses showed that plasma IL-6 levels were lower in women scoring
      higher on positive relationships, whereas sIL-6R levels were lower in women
      scoring higher on purpose in life, even after a variety of sociodemographic and
      health factors were controlled. These outcomes, combined with the absence of
      significant links with other measures of well-being and ill-being, suggest
      selective patterns of association between later life inflammatory processes and
      psychological factors, particularly those focused on positive ties with others
      and purposeful engagement.

PMID- 17500618
TI  - Desire for euthanasia or physician-assisted suicide in palliative cancer care.
AB  - OBJECTIVE: To investigate the attitudes of terminally ill individuals toward the
      legalization of euthanasia or physician-assisted suicide (PAS) and to identify
      those who would personally desire such a death. DESIGN: In the Canadian National
      Palliative Care Survey, semistructured interviews were administered to 379
      patients who were receiving palliative care for cancer. Patients who expressed a
      desire for physician-hastened death were followed prospectively. MAIN OUTCOME
      MEASURES: Attitudes toward the legalization of euthanasia or PAS were determined,
      as was the personal interest in receiving a hastened death. Demographic and
      clinical characteristics were also recorded, including a 22-item structured
      interview of symptoms and concerns. RESULTS: There were 238 participants (62.8%)
      who believed that euthanasia and/or PAS should be legalized, and 151 (39.8%) who
      would consider making a future request for a physician-hastened death. However,
      only 22 (5.8%) reported that, if legally permissible, they would initiate such a
      request right away, in their current situations. This desire for hastened death
      was associated with lower religiosity (p=.010), reduced functional status
      (p=.024), a diagnosis of major depression (p<.001), and greater distress on 12 of
      22 individual symptoms and concerns (p<.025). In follow-up interviews with 17
      participants, 2 (11.8%) showed instability in their expressed desire. CONCLUSION:
      Among patients receiving palliative care for cancer, the desire to receive
      euthanasia or PAS is associated with religious beliefs; functional status; and
      physical, social, and psychological symptoms and concerns. Although this desire
      is sometimes transitory, once firmly established, it can be enduring.

PMID- 17500619
TI  - Experiences of demand and control during daily life are predictors of carotid
      atherosclerotic progression among healthy men.
AB  - OBJECTIVES: The authors previously reported that individuals who rate their daily
      life as more demanding or less controllable by momentary electronic diary (ED)
      reports showed greater intima-medial thickness (IMT) by carotid ultrasonography.
      They now present prospective findings on this relation. DESIGN: Three hundred
      thirty-five healthy individuals (ages 50-70 at study onset) completed ongoing
      ratings of activity and mood over a 6-day period, using ED assessments. MAIN
      OUTCOME MEASURES: Mean bilateral carotid artery IMT was measured at baseline and
      36 months later. RESULTS AND CONCLUSION: Mean ratings of high demand and low
      control were significantly associated with IMT progression among men but not
      among women. These associations were not explained by traditional risk factors or
      by measures of occupational stress. Effects were partially accounted for by
      elevated ambulatory heart rates among those with low ratings of control. These
      data support the utility of ED-based measures for examining psychosocial risks in
      the prediction of cardiovascular disease progression.

PMID- 17500620
TI  - Does harboring hostility hurt? Associations between hostility and pulmonary
      function in the Coronary Artery Risk Development in (Young) Adults (CARDIA)
      study.
AB  - OBJECTIVE: To examine the cross-sectional association between hostility and
      pulmonary function (PF) and its consistency across race/ethnicity-gender groups.
      DESIGN: Data were from the Coronary Artery Risk Development in (Young) Adults
      (CARDIA) cohort study (N=4,629). Participants were recruited from 4 metropolitan
      areas in the United States, ages 18-30 years at baseline in 1985-1986,
      approximately balanced across race/ethnicity (Black, White) and gender. MAIN
      OUTCOME MEASURES: Main outcome measures were percent predicted values for forced
      expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). RESULTS: In
      full-sample multiple linear regression analyses, each 1 standard deviation (SD)
      increase in hostility was associated with a 0.66% decrease in FEV-sub-1 (p=.0002)
      and a 0.60% decrease in FVC (p=.0006). This inverse association of hostility with
      PF remained after controlling for age, height, current socioeconomic status
      (SES), participant smoking status, and asthma and is more consistent than that of
      smoking and PF. In stratified analyses, each 1 SD increase in hostility predicted
      statistically significant reductions in PF for Black women, White women, and
      Black men. For White men, hostility showed no statistically significant relation
      with PF, although the pattern relating hostility to PF was similar to the pattern
      in the other three groups. Further, both of the post hoc three-way interaction
      terms for hostility, race/ethnicity, and gender predicting FEV-sub-1 and FVC were
      nonsignificant. CONCLUSION: PF was inversely associated with hostility across
      race/ethnicity and gender, independent of age, height, current SES, smoking, and
      asthma. On the basis of these cross-sectional findings, the authors hypothesize
      that higher hostility will predict a more rapid decline in PF.

PMID- 17500621
TI  - Physical health problems, depressive mood, and cortisol secretion in old age:
      buffer effects of health engagement control strategies.
AB  - OBJECTIVE: This study examined the protective role played by control behaviors
      aimed at overcoming physical health problems (health engagement control
      strategies; HECS) in the associations between older adults' physical health
      problems, depressive mood, and diurnal cortisol secretion. It was expected that
      adaptive levels of HECS would buffer the adverse effects of physical health
      problems on depressive mood and diurnal cortisol secretion. DESIGN AND MEASURES:
      Physical health problems and HECS were measured in a cross-sectional sample of
      215 community-dwelling older adults. In addition, participants' depressive mood
      and patterns of diurnal cortisol secretion were assessed across 3 days. RESULTS:
      The findings demonstrate that physical health problems predicted high levels of
      depressive mood and diurnal cortisol secretion, but only among older adults who
      reported low levels of HECS (and not among older adults who reported high levels
      of HECS). Moreover, depressive mood completely mediated the buffering effect of
      HECS on the association between physical health problems and cortisol secretion.
      CONCLUSION: The results suggest that adaptive levels of HECS represent a
      psychological mechanism that can protect older adults from experiencing the
      adverse emotional and biological consequences of physical health problems.

PMID- 17500622
TI  - Long-term effects of appearance-based interventions on sun protection behaviors.
AB  - OBJECTIVES: To examine the longer term efficacies of exposure to UV photographs
      and photoaging information (e.g., wrinkles and age spots) for increasing sun
      protection intentions and behaviors of young adults. DESIGN: Randomized
      controlled trial with 4- to 5-month and 12-month follow-ups. MAIN OUTCOME
      MEASURES: Participants' self-reported sun protection intentions assessed
      immediately after the interventions, and both self-reported sun protection
      behaviors and an objective assessment (via spectrophotometry) of skin color
      change measured at the end of summer (4-5 months following interventions) and 1
      year following interventions. RESULTS: Both interventions resulted in immediate
      positive effects on future sun protection intentions. Both interventions showed
      objective evidence of less skin darkening at the postsummer follow-up, with those
      in the photoaging information condition also reporting more sun protective
      behavior and continuing to show less skin darkening 1 year after intervention.
      There was also evidence that effects of photoaging information on subsequent skin
      color change were mediated by the earlier positive effect photoaging information
      had on participants' intentions to sun protect and their subsequent sun
      protection behaviors. CONCLUSIONS: UV photo and photoaging-information
      interventions each show promise as a brief and relatively inexpensive approach
      for motivating sun protection practices that may reduce skin cancer risk.

PMID- 17500623
TI  - Joint effect of dopaminergic genes on likelihood of smoking following treatment
      with bupropion SR.
AB  - OBJECTIVE: To determine the relationship between joint variation in 2
      dopaminergic genes and the likelihood of nonsmoking following treatment with
      bupropion sustained release (SR). DESIGN: Three hundred twenty-three participants
      in a bupropion SR smoking cessation effectiveness trial with 12-month follow-up
      were genotyped for variants of dopamine receptor gene DRD2 and dopamine
      transporter SLC6A3. MAIN OUTCOME MEASURES: Self-reported 7-day point prevalence
      of nonsmoking. RESULTS: Neither genotype alone was associated with 7-day point
      prevalent nonsmoking at the 12-month follow-up. However, in the presence of the
      DRD2 A1 allele, SLC6A3 status was significantly associated with the likelihood of
      nonsmoking at the 12-month follow-up (individuals with DRD2 A1+ and SLC6A3 9-
      were more likely to be smoking). In the absence of the DRD2 A1 allele, the
      association between SLC6A3 status and nonsmoking was nonsignificant. CONCLUSION:
      Although these results are suggestive, a more compelling test is needed of the
      hypothesis that dopaminergic gene interaction underlies, in part, the likelihood
      of smoking following treatment with bupropion SR. Most likely this will come from
      larger studies involving prospective randomization to treatment based on
      genotype.

PMID- 17500624
TI  - Using motivational interviewing as a supplement to obesity treatment: a stepped
      care approach.
AB  - OBJECTIVE: This investigation was designed to improve behavioral weight loss
      program (BWLP) treatment outcomes by providing stepped care (SC) to individuals
      experiencing difficulties with weight loss during treatment. SC entails
      transition to more intensive treatments when less intensive treatments fail to
      meet treatment goals. In a BWLP, motivational interviewing (MI) may increase
      participants' motivation toward behavioral change and thus complement the
      acquisition of behavioral change skills. It was hypothesized that BWLP+SC (MI)
      participants (i.e., participants who failed to meet weight loss goals and
      received MI) would demonstrate superior treatment outcomes when compared with
      BWLP (SC matched) participants (i.e., participants who failed to meet weight loss
      goals but did not receive MI). DESIGN: Fifty-five obese, sedentary adults were
      randomly assigned to a BWLP+SC or a BWLP. MAIN OUTCOME MEASURES: Changes in
      weight, cardiorespiratory fitness, self-reported physical activity, and diet
      (i.e., calories, percentage daily intake of fat, protein, and carbohydrates) in
      response to treatment were assessed. RESULTS: Participants significantly
      decreased their weight, increased physical activity/fitness, and improved dietary
      intake (ps<.05). BWLP+SC (MI) participants lost more weight and engaged in
      greater weekly exercise than BWLP (SC matched) participants who did not receive
      MI (ps<.05). CONCLUSION: For individuals experiencing weight loss difficulties
      during a BWLP, MI may have considerable promise.

PMID- 17500625
TI  - Long-term follow-up of physical activity behavior in older adults.
AB  - OBJECTIVE: To examine the contribution of social-cognitive factors (self-efficacy
      and affect) in predicting long-term physical activity in a sample of older adults
      (N=174). DESIGN: A prospective design assessed physical activity and psychosocial
      variables at 2 and 5 years following a 6-month randomized, controlled exercise
      trial. MAIN OUTCOME MEASURES: The primary outcome variable was self-reported
      physical activity, with previous behavior, self-efficacy, and affect assessed as
      determinants of physical activity. RESULTS: Covariance modeling analyses
      indicated that physical activity at Year 2 was the strongest predictor of
      physical activity at 5-year follow-up. Both self-efficacy and affect at Year 2
      were also associated with physical activity at Year 5, as was original treatment
      condition. Variables accounted for 35% of the variance in Year 5 activity.
      CONCLUSION: Older adults with higher levels of physical activity, more positive
      affect, and higher self-efficacy at Year 2 were more likely to continue to be
      active at Year 5. This study is one of the longest follow-ups of exercise
      behavior in older adults and has implications for structuring environments to
      maximize the maintenance of physical activity.

PMID- 17500626
TI  - Topics in semantic representation.
AB  - Processing language requires the retrieval of concepts from memory in response to
      an ongoing stream of information. This retrieval is facilitated if one can infer
      the gist of a sentence, conversation, or document and use that gist to predict
      related concepts and disambiguate words. This article analyzes the abstract
      computational problem underlying the extraction and use of gist, formulating this
      problem as a rational statistical inference. This leads to a novel approach to
      semantic representation in which word meanings are represented in terms of a set
      of probabilistic topics. The topic model performs well in predicting word
      association and the effects of semantic association and ambiguity on a variety of
      language-processing and memory tasks. It also provides a foundation for
      developing more richly structured statistical models of language, as the
      generative process assumed in the topic model can easily be extended to
      incorporate other kinds of semantic and syntactic structure.

PMID- 17500627
TI  - Word learning as Bayesian inference.
AB  - The authors present a Bayesian framework for understanding how adults and
      children learn the meanings of words. The theory explains how learners can
      generalize meaningfully from just one or a few positive examples of a novel
      word's referents, by making rational inductive inferences that integrate prior
      knowledge about plausible word meanings with the statistical structure of the
      observed examples. The theory addresses shortcomings of the two best known
      approaches to modeling word learning, based on deductive hypothesis elimination
      and associative learning. Three experiments with adults and children test the
      Bayesian account's predictions in the context of learning words for object
      categories at multiple levels of a taxonomic hierarchy. Results provide strong
      support for the Bayesian account over competing accounts, in terms of both
      quantitative model fits and the ability to explain important qualitative
      phenomena. Several extensions of the basic theory are discussed, illustrating the
      broader potential for Bayesian models of word learning.

PMID- 17500628
TI  - Nested incremental modeling in the development of computational theories: the
      CDP+ model of reading aloud.
AB  - At least 3 different types of computational model have been shown to account for
      various facets of both normal and impaired single word reading: (a) the
      connectionist triangle model, (b) the dual-route cascaded model, and (c) the
      connectionist dual process model. Major strengths and weaknesses of these models
      are identified. In the spirit of nested incremental modeling, a new connectionist
      dual process model (the CDP+ model) is presented. This model builds on the
      strengths of 2 of the previous models while eliminating their weaknesses.
      Contrary to the dual-route cascaded model, CDP+ is able to learn and produce
      graded consistency effects. Contrary to the triangle and the connectionist dual
      process models, CDP+ accounts for serial effects and has more accurate nonword
      reading performance. CDP+ also beats all previous models by an order of magnitude
      when predicting individual item-level variance on large databases. Thus, the
      authors show that building on existing theories by combining the best features of
      previous models--a nested modeling strategy that is commonly used in other areas
      of science but often neglected in psychology--results in better and more powerful
      computational models.

PMID- 17500629
TI  - SD-squared: on the association between semantic dementia and surface dyslexia.
AB  - Within the connectionist triangle model of reading aloud, interaction between
      semantic and phonological representations occurs for all words but is
      particularly important for correct pronunciation of lower frequency exception
      words. This framework therefore predicts that (a) semantic dementia, which
      compromises semantic knowledge, should be accompanied by surface dyslexia, a
      frequency-modulated deficit in exception word reading, and (b) there should be a
      significant relationship between the severity of semantic degradation and the
      severity of surface dyslexia. The authors evaluated these claims with reference
      to 100 observations of reading data from 51 cases of semantic dementia. Surface
      dyslexia was rampant, and a simple composite semantic measure accounted for half
      of the variance in low-frequency exception word reading. Although in 3 cases
      initial testing revealed a moderate semantic impairment but normal exception word
      reading, all of these became surface dyslexic as their semantic knowledge
      deteriorated further. The connectionist account attributes such cases to
      premorbid individual variation in semantic reliance for accurate exception word
      reading. These results provide a striking demonstration of the association
      between semantic dementia and surface dyslexia, a phenomenon that the authors
      have dubbed SD-squared.

PMID- 17500631
TI  - Inhibitory control in mind and brain: an interactive race model of countermanding
      saccades.
AB  - The stop-signal task has been used to study normal cognitive control and clinical
      dysfunction. Its utility is derived from a race model that accounts for
      performance and provides an estimate of the time it takes to stop a movement.
      This model posits a race between go and stop processes with stochastically
      independent finish times. However, neurophysiological studies demonstrate that
      the neural correlates of the go and stop processes produce movements through a
      network of interacting neurons. The juxtaposition of the computational model with
      the neural data exposes a paradox-how can a network of interacting units produce
      behavior that appears to be the outcome of an independent race? The authors
      report how a simple, competitive network can solve this paradox and provide an
      account of what is measured by stop-signal reaction time.

PMID- 17500632
TI  - Interdependent sampling and social influence.
AB  - Most explanations of social influence focus on why individuals might want to
      agree with the opinions or attitudes of others. The authors propose a different
      explanation that assumes the attitudes of others influence only the activities
      and objects individuals are exposed to. For example, individuals are likely to be
      exposed to activities that their friends enjoy. The authors demonstrate that such
      influence over sampling behavior is sufficient to produce a social influence
      effect when individuals form attitudes by learning from experience. Even if the
      experiences of 2 individuals, when they sample an object or event, are
      independent random variables, their attitudes will become positively correlated
      if their sampling processes are interdependent. Interdependent sampling of
      activities thus provides a different explanation of social influence with
      distinct empirical and theoretical implications.

PMID- 17500633
TI  - Genetic and environmental influences on behavior: capturing all the interplay.
AB  - Basic quantitative genetic models of human behavioral variation have made clear
      that individual differences in behavior cannot be understood without
      acknowledging the importance of genetic influences. Yet these basic models
      estimate average, population-level genetic and environmental influences,
      obscuring differences that might exist within the population and masking
      systematic transactions between specific genetic and environmental influences.
      This article discusses a newer, more sophisticated and powerful quantitative
      genetic model that articulates these transactions. Results from this model
      highlight the ways in which the gene- environment interaction and correlation are
      intertwined. They can be used to integrate findings from quantitative and
      molecular genetic studies and to understand the roles of genetic influences and
      social forces in manifested behaviors, even when DNA sequence variation is not
      relevant.

PMID- 17500634
TI  - A distance judgment function based on space perception mechanisms: revisiting
      Gilinsky's (1951) equation.
AB  - In her seminal article in Psychological Review, A. S. Gilinsky (1951)
      successfully described the relationship between physical distance (D) and
      perceived distance (d) with the equation d = DA/(A + D), where A = constant. To
      understand its theoretical underpinning, the authors of the current article
      capitalized on space perception mechanisms based on the ground surface to derive
      the distance equation d = Hcosalpha/sin(alpha + eta), where H is the observer's
      eye height, alpha is the angular declination below the horizon, and eta is the
      slant error in representing the ground surface. Their equation predicts that (a)
      perceived distance is affected by the slant error in representing the ground
      surface; (b) when the slant error is small, the ground-based equation takes the
      same form as Gilinsky's equation; and (c) the parameter A in Gilinsky's equation
      represents the ratio of the observer's eye height to the sine of the slant error.
      These predictions were empirically confirmed, thus bestowing a theoretical
      foundation on Gilinsky's equation.

PMID- 17500630
TI  - Remembering the past and imagining the future: a neural model of spatial memory
      and imagery.
AB  - The authors model the neural mechanisms underlying spatial cognition, integrating
      neuronal systems and behavioral data, and address the relationships between long
      term memory, short-term memory, and imagery, and between egocentric and
      allocentric and visual and ideothetic representations. Long-term spatial memory
      is modeled as attractor dynamics within medial-temporal allocentric
      representations, and short-term memory is modeled as egocentric parietal
      representations driven by perception, retrieval, and imagery and modulated by
      directed attention. Both encoding and retrieval/imagery require translation
      between egocentric and allocentric representations, which are mediated by
      posterior parietal and retrosplenial areas and the use of head direction
      representations in Papez's circuit. Thus, the hippocampus effectively indexes
      information by real or imagined location, whereas Papez's circuit translates to
      imagery or from perception according to the direction of view. Modulation of this
      translation by motor efference allows spatial updating of representations,
      whereas prefrontal simulated motor efference allows mental exploration. The
      alternating temporal-parietal flows of information are organized by the theta
      rhythm. Simulations demonstrate the retrieval and updating of familiar spatial
      scenes, hemispatial neglect in memory, and the effects on hippocampal place cell
      firing of lesioned head direction representations and of conflicting visual and
      ideothetic inputs.

PMID- 17500635
TI  - Mechanisms of modal and amodal interpolation.
AB  - P. J. Kellman and T. F. Shipley (1992) and P. J. Kellman, P. Garrigan, and T. F.
      Shipley (2005) suggested that completion of partly occluded objects and illusory
      objects involve the same or similar mechanisms at critical stages of contour
      interpolation. B. L. Anderson, M. Singh, and R. W. Fleming and B. L. Anderson
      (2007) presented a number of arguments against this view. The author analyzes 3
      of these arguments, as well as B. L. Anderson's ecological justification for
      believing that these mechanisms must be very different, and suggests that their
      conclusions are unwarranted. The author also outlines a model consistent with the
      identity hypothesis and with recent physiological evidence, including a
      quantitative proposal for contour interpolation strength. The model suggests that
      V1 and V2 receive from higher visual areas feedback that modulates their
      responses to stimuli eliciting modal completion, amodal completion, and collinear
      contour facilitation. The model qualitatively explains the unstable percepts
      evoked by various recently devised stimuli.

PMID- 17500637
TI  - The demise of the identity hypothesis and the insufficiency and nonnecessity of
      contour relatability in predicting object interpolation: comment on Kellman,
      Garrigan, and Shipley (2005).
AB  - P. J. Kellman, P. Garrigan, and T. F. Shipley's theory of 3-dimensional object
      interpolation asserts that existing data, as well as logical considerations,
      support the view that an identical contour interpolation process underlies the
      interpolation of partially camouflaged and partially occluded objects (modal
      completion and amodal completion, respectively). Here, the author argues that
      recent data show that this theory is incorrect and that the logical arguments
      offered in support of the identity hypothesis depend on specific unverified
      models of the phenomena in question. Alternative explanations of these effects
      are developed to show that such phenomena do not logically implicate an identity
      hypothesis and, in some cases, provide strong evidence against the identity
      hypothesis. Finally, the author describes several completion phenomena that
      reveal that the relatability criteria embodied in Kellman et al.'s model are
      neither necessary nor sufficient for understanding the interpolation processes
      the model was designed to explain.

PMID- 17500638
TI  - Interpolation processes in object perception: reply to Anderson (2007).
AB  - P. J. Kellman, P. Garrigan, & T. F. Shipley presented a theory of 3-D
      interpolation in object perception. Along with results from many researchers,
      this work supports an emerging picture of how the visual system connects separate
      visible fragments to form objects. In his commentary, B. L. Anderson challenges
      parts of that view, especially the idea of a common underlying interpolation
      component in modal and amodal completion (the identity hypothesis). Here the
      authors analyze Anderson's evidence and argue that he neither provides any reason
      to abandon the identity hypothesis nor offers a viable alternative theory. The
      authors offer demonstrations and analyses indicating that interpolated contours
      can appear modally despite absence of the luminance relations, occlusion
      geometry, and surface attachment that Anderson claims to be necessary. The
      authors elaborate crossing interpolations as key cases in which modal and amodal
      appearance must be consequences of interpolation. Finally, the authors dispute
      Anderson's assertion that vision researchers are misguided in using objective
      performance methods, and they argue that his challenges to relatability fail
      because contour and surface processes, as well as local and global influences,
      have been distinguished experimentally.

PMID- 17500640
TI  - Filling-in models of completion: rejoinder to Kellman, Garrigan, Shipley, and
      Keane (2007) and Albert (2007).
AB  - There has been a growing interest in understanding the computations involved in
      the processes underlying visual segmentation and interpolation in conditions of
      occlusion. P. J. Kellman, P. Garrigan, T. F. Shipley, and B. P. Keane and M. K.
      Albert defended the view that identical contour interpolation mechanisms underlie
      modal and amodal completion. In the current rejoinder, the author provides
      further psychophysical evidence against this view and argues that no
      physiological data support the claim that modal and amodal contours are
      represented identically at any stage of processing. The author also shows that
      the illusory glass surfaces that Kellman et al. and Albert upheld as evidence
      against his arguments about luminance constraints in completion are explained by
      theoretical principles that he has previously articulated, and variants of these
      illusions receive no explanation within either of the models Kellman et al. and
      Albert propose. The author shows that the principles needed to explain these
      percepts embody fundamental asymmetries in the way that relative depth shapes
      segmentation and interpolation processes and that models of completion that lack
      these constraints--such as P. J. Kellman, P. Garrigan, and T. F. Shipley's and M.
      K. Albert's --cannot account for a host of documented completion phenomena.

PMID- 17500642
TI  - Is absolute identification always relative? Comment on Stewart, Brown, and Chater
      (2005).
AB  - N. Stewart, G. D. A. Brown, and N. Chater's relative judgment model includes
      three core assumptions that enable it to predict accurately the vast majority of
      "classical" phenomena in absolute identification choices, but not the time taken
      to make them, including sequential effects, such as assimilation and contrast.
      These core assumptions, coupled with the parameter values used in the above
      mentioned article, lead to the prediction that identification accuracy is low
      when a large stimulus on 1 trial is followed by a small stimulus on the next
      trial and vice versa. Data do not support this prediction. The authors identify a
      set of parameters that allow the model to better fit the data, but problems
      remain when the data are analyzed with a version of the discrimination measure
      (d') from signal detection theory. The fundamental problem is that the model fits
      data on average but at the expense of making incorrect predictions in detail.

PMID- 17500643
TI  - Absolute identification is relative: a reply to Brown, Marley, and Lacouture
      (2007).
AB  - N. Stewart, G. D. A. Brown, and N. Chater presented a relative judgment model
      (RJM) of absolute identification, in which the current stimulus is judged
      relative to the preceding stimulus. S. Brown, A. A. J. Marley, and Y. Lacouture
      found that the RJM does not predict their finding of increased accuracy after
      large stimulus jumps, except at the expense of other effects. In fact, the RJM
      does predict both the core effects and increased accuracy after large jumps
      (although it underestimates this effect) when better constrained parameters are
      estimated from the trial-by-trial raw data rather than from summary plots.
      Further, a modified RJM, in which the stimulus from two trials ago is sometimes
      used as a referent, provides a better fit.

PMID- 17500644
TI  - Sleep's function in the spontaneous recovery and consolidation of memories.
AB  - Building on 2 previous studies (B. R. Ekstrand, 1967; B. R. Ekstrand, M. J.
      Sullivan, D. F. Parker, & J. N. West, 1971), the authors present 2 experiments
      that were aimed at characterizing the role of retroactive interference in sleep
      associated declarative memory consolidation. Using an A-B, A-C paradigm with
      lists of word pairs in Experiment 1, the authors showed that sleep provides
      recovery from retroactive interference induced at encoding, whereas no such
      recovery was seen in several wake control conditions. Noninterfering word-pair
      lists were used in Experiment 2 (A-B, C-D). Sleeping after learning, in
      comparison with waking after learning, enhanced retention of both lists to a
      similar extent when encoding was less intense because of less list repetition and
      briefer word-pair presentations. With intense encoding, sleep-associated
      improvements were not seen for either list. In combination, the results indicate
      that the benefit of sleep for declarative memory consolidation is greater for
      weaker associations, regardless of whether weak associations result from
      retroactive interference or poor encoding.

PMID- 17500645
TI  - Metacognition of agency.
AB  - The feeling that we are agents, intentionally making things happen by our own
      actions, is foundational to our understanding of ourselves as humans. People's
      metacognitions of agency were investigated in 4 experiments. Participants played
      a game in which they tried to touch downward scrolling Xs and avoid touching Os.
      Variables that affected accuracy included speed of the scroll, density of the
      targets, and feedback. Of central interest were variables directed not only at
      accuracy but also at people's control: the turbulence of the cursor and how close
      the cursor had to come to the target for a hit (i.e., "magic"). After each trial,
      people made judgments of agency or judgments of performance. People were
      selectively sensitive to the variables to which they should be responsive in
      agency monitoring--whether the cursor moved in close synchrony to their movements
      and whether targets disappeared by magic. People knew, separably from their
      objective or judged performance, when they were in control and when they were
      not. These results indicate that people can sensitively monitor their own agency.

PMID- 17500646
TI  - Probabilistic retroactive interference: the role of accessibility bias in
      interference effects.
AB  - Probabilistic retroactive interference (RI) refers to the interfering effects of
      intermixing presentations of an earlier studied response (A-B) with presentations
      of a competing response (A-D). As an example, for a 2/3 condition, a cue word was
      presented with its earlier studied response twice and its competing response once
      during the interference phase. Performance on direct and indirect tests of memory
      for earlier studied responses was combined to reveal dissociations between
      effects on recollection and accessibility bias. Manipulating probabilistic RI
      influenced accessibility bias but left recollection unchanged. Effects of
      probabilistic RI were compared with effects of traditional, nonprobabilistic RI.
      The authors contrast their dual-process model with traditional accounts of RI and
      discuss the importance of distinguishing between recollection and accessibility
      bias for understanding interference effects.

PMID- 17500647
TI  - Focusing the spotlight: individual differences in visual attention control.
AB  - A time-course analysis of visual attention focusing (attentional constraint) was
      conducted in groups of participants with high and low working memory spans, a
      dimension the authors have argued reflects the ability to control attention. In 4
      experiments, participants performed the Eriksen flanker paradigm under increasing
      levels of speed stress. Conditional accuracy functions were derived to measure
      the time course of attentional constraint. The data showed that accuracy rates
      rose toward asymptote at different rates, with participants with high working
      memory spans reaching peak performance before participants with low working
      memory spans. The authors interpret these data in terms of a rate of attention
      constraint model.

PMID- 17500649
TI  - Attention control, memory updating, and emotion regulation temporarily reduce the
      capacity for executive control.
AB  - This research tested the hypothesis that initial efforts at executive control
      temporarily undermine subsequent efforts at executive control. Four experiments
      revealed that controlling the focus of visual attention (Experiment 1),
      inhibiting predominant writing tendencies (Experiment 2), taking a working memory
      test (Experiment 3), or exaggerating emotional expressions (Experiment 4)
      undermined performance on subsequent tests of working memory span, reverse digit
      span, and response inhibition, respectively. The results supported a limited
      resource model of executive control and cast doubt on competing accounts based on
      mood, motivation, or task difficulty. Prior efforts at executive control are a
      significant contextual determinant of the operation of executive processes.

PMID- 17500650
TI  - Stereotype threat and working memory: mechanisms, alleviation, and spillover.
AB  - Stereotype threat (ST) occurs when the awareness of a negative stereotype about a
      social group in a particular domain produces suboptimal performance by members of
      that group. Although ST has been repeatedly demonstrated, far less is known about
      how its effects are realized. Using mathematical problem solving as a test bed,
      the authors demonstrate in 5 experiments that ST harms math problems that rely
      heavily on working memory resources--especially phonological aspects of this
      system. Moreover, by capitalizing on an understanding of the cognitive mechanisms
      by which ST exerts its impact, the authors show (a) how ST can be alleviated
      (e.g., by heavily practicing once-susceptible math problems such that they are
      retrieved directly from long-term memory rather than computed via a working
      memory-intensive algorithm) and (b) when it will spill over onto subsequent tasks
      unrelated to the stereotype in question but dependent on the same cognitive
      resources that stereotype threat also uses. The current work extends the
      knowledge of the causal mechanisms of stereotype threat and demonstrates how its
      effects can be attenuated and propagated.

PMID- 17500651
TI  - Where there is a way, is there a will? The effect of future choices on self
      control.
AB  - Choices often involve self-control conflicts such that options that are
      immediately appealing are less desirable in the long run. In the current
      research, the authors examine how viewing such a choice as one of a series of
      similar future choices rather than as an isolated decision decreases the
      preference for items requiring self-control. The authors show that (a) in a
      choice between a vice and a virtue, the share choosing vice increases when the
      decision is presented as one of a series of similar future choices versus when
      the same choice is viewed in isolation, and (b) the overall share choosing a vice
      increases when decisions are seen in connection with similar future choices. The
      findings contrast with the general wisdom that broader choice frames lead to the
      exercise of greater self-control. The authors propose that the context of similar
      future choices allows people to optimistically believe that they will choose a
      virtue in the future choice and hence provides them with a guilt-reducing
      justification to not exercise self-control in the present.

PMID- 17500652
TI  - Looking forward, looking back: anticipation is more evocative than retrospection.
AB  - The results of 5 experiments indicate that people report more intense emotions
      during anticipation of, than during retrospection about, emotional events that
      were positive (Thanksgiving Day), negative (annoying noises, menstruation),
      routine (menstruation), and hypothetical (all-expenses-paid ski vacation).
      People's tendency to report more intense emotion during anticipation than during
      retrospection was associated with a slight, but only occasionally significant,
      tendency for people to expect future emotions to be more intense than they
      remembered past emotions having been. The greater evocativeness of anticipation
      than retrospection was also associated with and statistically mediated by
      participants' tendency to report mentally simulating future emotional events more
      extensively than they report mentally stimulating past emotional events. The
      conclusion that anticipation is more evocative than retrospection has
      implications for research methodology, clinical practice, decision making, and
      well-being.

PMID- 17500653
TI  - Directed forgetting of recently recalled autobiographical memories.
AB  - In 6 experiments, the authors investigated list-method directed forgetting of
      recently recalled autobiographical memories. Reliable directed forgetting effects
      were observed across all experiments. In 4 experiments, the authors examined the
      impact of memory valence on directed forgetting. The forget instruction impaired
      recall of negative, positive, and neutral memories equally, although overall,
      participants recalled fewer unemotional memories than emotional memories. The
      preexisting organization of memories enhanced the directed forgetting effect, and
      a release from forgetting occurred only when the forgotten memories were directly
      cued. The authors discuss the roles of emotion, retrieval dynamics, and
      organization in these effects and suggest that the directed forgetting of
      recently recalled autobiographical memories may reflect the inhibition of
      recently formed memories of remembering, that is, episodic inhibition. The
      authors consider the implications of these findings for the control of
      autobiographical remembering in everyday life.

PMID- 17500654
TI  - Graded semantic and phonological similarity effects in priming: evidence for a
      distributed connectionist approach to morphology.
AB  - A considerable body of empirical and theoretical research suggests that
      morphological structure governs the representation of words in memory and that
      many words are decomposed into morphological components in processing. The
      authors investigated an alternative approach in which morphology arises from the
      interaction of semantic and phonological codes. A series of cross-modal lexical
      decision experiments shows that the magnitude of priming reflects the degree of
      semantic and phonological overlap between words. Crucially, moderately similar
      items produce intermediate facilitation (e.g., lately-late). This pattern is
      observed for word pairs exhibiting different types of morphological
      relationships, including suffixed-stem (e.g., teacher-teach), suffixed-suffixed
      (e.g., saintly-sainthood), and prefixed-stem pairs (preheat-heat). The results
      can be understood in terms of connectionist models that use distributed
      representations rather than discrete morphemes.

PMID- 17500655
TI  - Majority model on a network with communities.
AB  - We focus on the majority model in a topology consisting of two coupled fully
      connected networks, thereby mimicking the existence of communities in social
      networks. We show that a transition takes place at a value of the
      interconnectivity parameter. Above this value, only symmetric solutions prevail,
      where both communities agree with each other and reach consensus. Below this
      value, in contrast, the communities can reach opposite opinions and an asymmetric
      state is attained. The importance of the interface between the subnetworks is
      shown.

PMID- 17500656
TI  - Self-affinity in the gradient percolation problem.
AB  - We study the scaling properties of the solid-on-solid front of the infinite
      cluster in two-dimensional gradient percolation. We show that such an object is
      self-affine with a Hurst exponent equal to 23 up to a cutoff length approximately
      g{-4/7}, where g is the gradient. Beyond this length scale, the front position
      has the character of uncorrelated noise. Importantly, the self-affine behavior is
      robust even after removing local jumps of the front. The previously observed
      multiaffinity is due to the dominance of overhangs at small distances in the
      structure function. This is a crossover effect.

PMID- 17500657
TI  - Two simple models of classical heat pumps.
AB  - Motivated by recent studies of models of particle and heat quantum pumps, we
      study similar simple classical models and examine the possibility of heat
      pumping. Unlike many of the usual ratchet models of molecular engines, the models
      we study do not have particle transport. We consider a two-spin system and a
      coupled oscillator system which exchange heat with multiple heat reservoirs and
      which are acted upon by periodic forces. The simplicity of our models allows
      accurate numerical and exact solutions and unambiguous interpretation of results.
      We demonstrate that while both our models seem to be built on similar principles,
      one is able to function as a heat pump (or engine) while the other is not.

PMID- 17500658
TI  - Superaging in two-dimensional random ferromagnets.
AB  - We study the aging properties, in particular the two-time autocorrelations, of
      the two-dimensional randomly diluted Ising ferromagnet below the critical
      temperature via Monte Carlo simulations. We find that the autocorrelation
      function displays additive aging C(t,t{w})=C{st}(t)+C{ag}(t,t{w}), where the
      stationary part Cst} decays algebraically. The aging part shows anomalous scaling
      C{ag}(t,t{w})=C[h(t)h(t{w})], where h(u) is a nonhomogeneous function excluding a
      t/t{w} scaling.

PMID- 17500659
TI  - Universal anisotropy in force networks under shear.
AB  - Scaling properties of patterns formed by large contact forces are studied as a
      function of the applied shear stress, in two-dimensional static packings
      generated from the force network ensemble. An anisotropic finite-size-scaling
      analysis shows that the applied shear does not affect the universal scaling
      properties of these patterns, but simply induces different length scales in the
      principal directions of the macroscopic stress tensor. The ratio of these length
      scales quantifies the anisotropy of the force networks, and is found not to
      depend on the details of the underlying contact network, in contrast with other
      properties such as the yield stress.

PMID- 17500660
TI  - Screwlike order, macroscopic chirality, and elastic distortions in high-density
      DNA mesophases.
AB  - We investigate a new screwlike liquid-crystalline ordering in solutions of
      helical biopolymers and its influence on the state of individual molecules. In
      the resulting mesophase translational and rotational motions of molecules are
      coupled in screw fluctuations. We show that in contrast to the case of
      conventional chiral liquid crystals the elastic distortion does not twist the
      screw order but leads to overwinding of individual helical molecules. This
      explains the peculiarities of high-density DNA mesophases.

PMID- 17500661
TI  - Effects of temperature on the mechanical properties of single stranded DNA.
AB  - We present the first measurements of the temperature dependent extension of
      single stranded DNA. At forces between 2 and 10 pN the extension increases with
      temperature. This increase in extension is consistent with the disruption of
      hairpins, and a simple theory that includes hairpin formation shows good
      agreement with the data at these low forces. In contrast, at forces above 10 pN
      and temperatures higher than 40 degrees C, the extension decreases rapidly with
      temperature in a manner not consistent with predictions.

PMID- 17500662
TI  - Inertial effects in the fractional translational diffusion of a Brownian particle
      in a double-well potential.
AB  - The anomalous translational diffusion including inertial effects of nonlinear
      Brownian oscillators in a double well potential V(x)=ax{2}/2+bx{4}/4 is
      considered. An exact solution of the fractional Klein-Kramers (Fokker-Planck)
      equation is obtained allowing one to calculate via matrix continued fractions the
      positional autocorrelation function and dynamic susceptibility describing the
      position response to a small external field. The result is a generalization of
      the solution for the normal Brownian motion in a double well potential to
      fractional dynamics (giving rise to anomalous diffusion).

PMID- 17500663
TI  - Transient nucleation near the mean-field spinodal.
AB  - Nucleation is considered near the pseudo-spinodal in a one-dimensional phi{4}
      model with a nonconserved order parameter and long-range interactions. For a
      sufficiently large system or a system with slow relaxation to metastable
      equilibrium, there is a non-negligible probability of nucleation occurring before
      reaching metastable equilibrium. This process is referred to as transient
      nucleation. The critical droplet is defined to be the configuration of maximum
      likelihood that is dynamically balanced between the metastable and stable wells.
      Time-dependent droplet profiles and nucleation rates are derived, and theoretical
      results are compared to computer simulations. The analysis reveals a distribution
      of nucleation times with a distinct peak characteristic of a nonstationary
      nucleation rate. Under the quench conditions employed, transient critical
      droplets are more compact than the droplets found in metastable equilibrium
      simulations and theoretical predictions.

PMID- 17500664
TI  - Freezing transition of the random bond RNA model: Statistical properties of the
      pairing weights.
AB  - To characterize the pairing specificity of RNA secondary structures as a function
      of temperature, we analyze the statistics of the pairing weights as follows: for
      each base (i) of the sequence of length N , we consider the (N-1) pairing weights
      w{i}(j) with the other bases (j not equal i) of the sequence. We numerically
      compute the probability distributions P1(w) of the maximal weight
      w[{i}{max}=max{j}[w{i}(j)] , the probability distribution Pi(Y(2)) of the
      parameter Y2(i)= summation operator{j}w{i}{2}(j) , as well as the average values
      of the moments Y{k}(i)= summation operator_{j}w_{i}{k}(j) . We find that there
      are two important temperatures T_{c}<T_{gap} . For T>T_{gap} , the distribution
      P1(w) vanishes at some value w{0}(T)<1 , and accordingly the moments Y{k}(i)
      decay exponentially as [w{0}(T)]{k} in k . For T<T{gap} , the distributions P1(w)
      and Pi(Y2) present the characteristic Derrida-Flyvbjerg singularities at w=1n and
      Y{2}=1/n for n=1,2,... . In particular, there exists a temperature-dependent
      exponent mu(T) that governs the singularities P1(w) approximately (1-w){mu(T)-1}
      and Pi(Y2) approximately (1-Y{2}){mu(T)-1} as well as the power-law decay of the
      moments Y{k}(i) approximately 1k{mu(T)} . The exponent mu(T) grows from the value
      mu(T=0)=0 up to mu(T{gap}) approximately 2 . The study of spatial properties
      indicates that the critical temperature T{c} where the large-scale roughness
      exponent changes from the low temperature value zeta approximately 0.67 to the
      high temperature value zeta approximately 0.5 corresponds to the exponent
      mu(T{c})=1 . For T<T{c} , there exists frozen pairs of all sizes, whereas for
      T{c}<T<T{gap} , there exists frozen pairs, but only up to some characteristic
      length diverging as xi(T) approximately 1(T{c}-T){nu} with nu approximately 2 .
      The similarities and differences with the weight statistics in Levy sums and in
      Derrida's random energy model are discussed.

PMID- 17500665
TI  - Scaling approach to related disordered stochastic and free-fermion models.
AB  - Motivated by mapping from a stochastic system with spatially random rates, we
      consider disordered non-conserving free-fermion systems using a scaling procedure
      for the equations of motion. This approach demonstrates disorder-induced
      localization acting in competition with the asymmetric driving. We discuss the
      resulting implications for the original stochastic system.

PMID- 17500666
TI  - Critical wetting of a class of nonequilibrium interfaces: a mean-field picture.
AB  - A self-consistent mean-field method is used to study critical wetting transitions
      under nonequilibrium conditions by analyzing Kardar-Parisi-Zhang (KPZ) interfaces
      in the presence of a bounding substrate. In the case of positive KPZ nonlinearity
      a single (Gaussian) regime is found. On the contrary, interfaces corresponding to
      negative nonlinearities lead to three different regimes of critical behavior for
      the surface order parameter: (i) a trivial Gaussian regime, (ii) a weak
      fluctuation regime with a trivially located critical point and nontrivial
      exponents, and (iii) a highly nontrivial strong-fluctuation regime, for which we
      provide a full solution by finding the zeros of parabolic-cylinder functions.
      These analytical results are also verified by solving numerically the self
      consistent equation in each case. Analogies with and differences from equilibrium
      critical wetting as well as nonequilibrium complete wetting are also discussed.

PMID- 17500667
TI  - Gaussian noise and time-reversal symmetry in nonequilibrium Langevin models.
AB  - We show that in driven systems the Gaussian nature of the fluctuating force and
      time reversibility are equivalent properties. This result together with the
      potential condition of the external force drastically restricts the form of the
      probability distribution function, which can be shown to satisfy time-independent
      relations. We have corroborated this feature by explicitly analyzing a model for
      the stretching of a polymer and a model for a suspension of noninteracting
      Brownian particles in steady flow.

PMID- 17500668
TI  - Dynamics of quantum dissipation systems interacting with bosonic canonical bath:
      hierarchical equations of motion approach.
AB  - A nonperturbative theory is developed, aiming at an exact and efficient
      evaluation of a general quantum system interacting with arbitrary bath
      environment at any temperature and in the presence of arbitrary time-dependent
      external fields. An exact hierarchical equations of motion formalism is
      constructed on the basis of a calculus-on-path-integral algorithm, via the
      auxiliary influence generating functionals related to the interaction bath
      correlation functions in a parametrization expansion form. The corresponding
      continued-fraction Green's functions formalism for quantum dissipation is also
      presented. Proposed further is the principle of residue correction, not just for
      truncating the infinite hierarchy, but also for incorporating the small residue
      dissipation that may arise from the practical difference between the true and
      parametrized bath correlation functions. The final residue-corrected hierarchical
      equations of motion can therefore be used practically for the evaluation of
      arbitrary dissipative quantum systems.

PMID- 17500669
TI  - Shot noise displaying simultaneously the Noah and Joseph effects.
AB  - Shot noise processes displaying the Noah effect are of infinite variance. Hence
      the measurement of the correlation structure of such processes--indicating
      whether the Joseph effect is displayed as well--cannot be conducted via their
      autocovariance functions (which are undefined). To circumvent this problem, a
      Poisson-based analysis applicable to shot noise processes with infinite variance,
      as well as to shot noise processes with divergent noise levels, is developed. A
      Poissonian autocovariance function, which characterizes the process-distribution
      of general shot noise processes, is introduced. In particular, this function
      governs and quantifies the processes' stationary structure (amplitudal behavior)
      and correlation structure (temporal behavior). The "Poissonian methodology"
      developed enables a precise quantitative analysis of shot noise processes
      displaying simultaneously the Noah and Joseph effects.

PMID- 17500670
TI  - Irreducible memory function and slow dynamics in disordered systems.
AB  - We show how the irreducible memory function can be obtained in a rather
      straightforward way, and that it can be expressed in terms of two contributions
      representing two parallel decay channels. This representation should be useful
      for treating systems with a slow time dependence and where eventually some
      internal degrees of freedom enters in the relaxation process, and cuts off an
      underlying ideal ergodic to nonergodic transition. We also show how the
      irreducible memory function under certain mild conditions defines a regenerative
      stochastic process, or a two level stochastic system. This leads to a picture
      with dynamical heterogeneities, where the statistical properties asymptotically
      are ruled by limit processes. This can explain the universal behavior observed in
      many glass-forming systems.

PMID- 17500671
TI  - Finite-size scaling in anisotropic systems.
AB  - We present analytical results for the finite-size scaling in d-dimensional O(N)
      systems with strong anisotropy where the critical exponents (e.g., nu{ ||} and
      nu{ perpendicular}) depend on the direction. Prominent examples are systems with
      long-range interactions, decaying with the interparticle distance r as r{-d
      sigma} with different exponents sigma in corresponding spatial directions,
      systems with space-"time" anisotropy near a quantum critical point, and systems
      with Lifshitz points. The anisotropic properties involve also the geometry of the
      systems. We consider O(N) systems in the N-->infinity limit, confined to a d
      dimensional layer with geometry L{m} X infinity {n};m+n=d and periodic boundary
      conditions across the finite m dimensions. The arising difficulties are avoided
      using a technique of calculations based on the analytical properties of the
      generalized Mittag-Leffler functions.

PMID- 17500672
TI  - Kinetics of self-induced aggregation in Brownian particles.
AB  - We study a model of interacting random walkers that proposes a simple mechanism
      for the emergence of cooperation in a group of individuals. Each individual,
      represented by a Brownian particle, experiences an interaction produced by the
      local unbalance in the spatial distribution of the other individuals. This
      interaction results in a nonlinear velocity driving the particle trajectories in
      the direction of the nearest more crowded region; the competition among different
      aggregating centers generates nontrivial dynamical regimes. Our simulations show
      that for sufficiently low randomness the system evolves through a coalescence
      behavior characterized by clusters of particles growing with a power law in time.
      In addition, the typical scaling properties of the general theory of stochastic
      aggregation processes are verified.

PMID- 17500673
TI  - Criticality of a contact process with coupled diffusive and non-diffusive fields.
AB  - We investigate the critical behavior of a model with two coupled critical
      densities, one of which is diffusive. The model simulates the propagation of an
      epidemic process in a population, which uses the underlying lattice to leave a
      track of the recent disease history. We determine the critical density of the
      population above which the system reaches an active stationary state with a
      finite density of active particles. We also perform a scaling analysis to
      determine the order parameter, the correlation length, and critical relaxation
      exponents. We show that the model does not belong to the usual directed
      percolation universality class and is compatible with the class of directed
      percolation with diffusive and conserved fields.

PMID- 17500674
TI  - Statistical scattering of waves in disordered waveguides: From microscopic
      potentials to limiting macroscopic statistics.
AB  - We study the statistical properties of wave scattering in a disordered waveguide.
      The statistical properties of a "building block" of length deltaL are derived
      from a potential model and used to find the evolution with length of the
      expectation value of physical quantities. In the potential model the scattering
      units consist of thin potential slices, idealized as delta slices, perpendicular
      to the longitudinal direction of the waveguide; the variation of the potential in
      the transverse direction may be arbitrary. The sets of parameters defining a
      given slice are taken to be statistically independent from those of any other
      slice and identically distributed. In the dense-weak-scattering limit, in which
      the potential slices are very weak and their linear density is very large, so
      that the resulting mean free paths are fixed, the corresponding statistical
      properties of the full waveguide depend only on the mean free paths and on no
      other property of the slice distribution. The universality that arises
      demonstrates the existence of a generalized central-limit theorem. Our final
      result is a diffusion equation in the space of transfer matrices of our system,
      which describes the evolution with the length L of the disordered waveguide of
      the transport properties of interest. In contrast to earlier publications, in the
      present analysis the energy of the incident particle is fully taken into account.
      For one propagating mode, N=1 , we have been able to solve the diffusion equation
      for a number of particular observables, and the solution is in excellent
      agreement with the results of microscopic calculations. In general, we have not
      succeeded in finding a solution of the diffusion equation. We have thus developed
      a numerical simulation, to be called "random walk in the transfer matrix space,"
      in which the universal statistical properties of a "building block" are first
      implemented numerically, and then the various building blocks are combined to
      find the statistical properties of the full waveguide. The reported results thus
      obtained (in which use was made of a "short-wavelength approximation") are in
      very good agreement with those arising from truly microscopic calculations, for
      both bulk and surface disorder. Since the paper has a clear pedagogical aim, we
      have included, for the benefit of experts and non-experts, a number of appendixes
      that contain the more involved calculations.

PMID- 17500675
TI  - Structure of fluctuations near mean-field critical points and spinodals and its
      implication for physical processes.
AB  - We analyze the structure of fluctuations near critical points and spinodals in
      mean-field and near-mean-field systems. Unlike systems that are non-mean-field,
      for which a fluctuation can be represented by a single cluster in a properly
      chosen percolation model, a fluctuation in mean-field and near-mean-field systems
      consists of a large number of clusters, which we term fundamental clusters. The
      structure of the latter and the way that they form fluctuations has important
      physical consequences for phenomena as diverse as nucleation in supercooled
      liquids, spinodal decomposition and continuous ordering, and the statistical
      distribution of earthquakes. The effects due to the fundamental clusters implies
      that they are physical objects and not only mathematical constructs.

PMID- 17500676
TI  - Influence of external magnetic field on dynamics of open quantum systems.
AB  - The influence of an external magnetic field on the non-Markovian dynamics of an
      open two-dimensional quantum system is investigated. The fluctuations of
      collective coordinate and momentum and transport coefficients are studied for a
      charged harmonic oscillator linearly coupled to a neutral bosonic heat bath. It
      is shown that the dissipation of collective energy slows down with increasing
      strength of the external magnetic field. The role of magnetic field in the
      diffusion processes is illustrated by several examples.

PMID- 17500677
TI  - Level dynamics approach to the large deviation statistical characteristic
      function.
AB  - We propose a level dynamics approach to the large deviation statistical
      characteristic function phi(q) for temporal series of dynamical variable V, which
      is the largest eigenvalue of the generalized evolution operator H{q}(identical
      with H+qV). This is done first by deriving "equations of motion" for the
      eigenvalues and the eigenstates of H{q} with the initial conditions determined by
      those of H , the true evolution operator for the dynamical variable under
      consideration, and then by solving these equations. Furthermore, utilizing simple
      solvable models, it is shown that the eigenvalues and eigenstates satisfy the
      equations of motion derived in this paper.

PMID- 17500678
TI  - Directing Brownian motion by oscillating barriers.
AB  - We consider the Brownian motion of a colloidal particle in a symmetric, periodic
      potential, whose potential barriers are subjected to temporal oscillations.
      Experimentally, the potential is generated by two arrays of trapped, negatively
      charged particles whose positions are periodically modulated with light forces.
      This results in a structured channel geometry of locally variable width. If all
      potential barriers are oscillating in synchrony, a resonance-like peak of the
      effective diffusion coefficient upon variation of the oscillation period is
      observed. For asynchronously oscillating barriers, the particle can be steered
      with great reliability into one or the other direction by properly choosing the
      oscillation periods of the different barriers along the channel.

PMID- 17500679
TI  - Role of interactions in ferrofluid thermal ratchets.
AB  - Orientational fluctuations of colloidal particles with magnetic moments may be
      rectified with the help of external magnetic fields with suitably chosen time
      dependence. As a result a noise-driven rotation of particles occurs giving rise
      to a macroscopic torque per volume of the carrier liquid. We investigate the
      influence of mutual interactions between the particles on this ratchet effect by
      studying a model system with mean-field interactions. The stochastic dynamics may
      be described by a nonlinear Fokker-Planck equation for the collective orientation
      of the particles which we solve approximately by using the effective field
      method. We determine an interval for the ratio between coupling strength and
      noise intensity for which a self-sustained rectification of fluctuations becomes
      possible. The ratchet effect then operates under conditions for which it was
      impossible in the absence of interactions.

PMID- 17500680
TI  - Smoothing a rock by chipping.
AB  - We investigate an idealized model for the size reduction and smoothing of a
      polygonal rock due to repeated chipping at corners. Each chip is sufficiently
      small so that only a single corner and a fraction of its two adjacent sides are
      cut from the object in a single chipping event. After many chips have been cut
      away, the resulting shape of the rock is generally anisotropic, with facet
      lengths and corner angles distributed over a broad range. Although a well-defined
      shape is quickly reached for each realization, there are large fluctuations
      between realizations.

PMID- 17500681
TI  - Intensive thermodynamic parameters in nonequilibrium systems.
AB  - Considering a broad class of steady-state nonequilibrium systems for which some
      additive quantities are conserved by the dynamics, we introduce from a
      statistical approach intensive thermodynamic parameters (ITPs) conjugated to the
      conserved quantities. This definition does not require any detailed balance
      relation to be fulfilled. Rather, the system must satisfy a general additivity
      property, which holds in most of the models usually considered in the literature,
      including those described by a matrix product ansatz with finite matrices. The
      main property of these ITPs is to take equal values in two subsystems, making
      them a powerful tool to describe nonequilibrium phase coexistence, as illustrated
      on different models. We finally discuss the issue of the equalization of ITPs
      when two different systems are put into contact. This issue is closely related to
      the possibility of measuring the ITPs using a small auxiliary system, in the same
      way as temperature is measured with a thermometer, and points at one of the major
      difficulties of nonequilibrium statistical mechanics. In addition, an efficient
      alternative determination, based on the measure of fluctuations, is also proposed
      and illustrated.

PMID- 17500682
TI  - Localization of coherent exciton transport in phase space.
AB  - We study numerically the dynamics of excitons on discrete rings in the presence
      of static disorder. Based on continuous-time quantum walks we compute the time
      evolution of the Wigner function (WF) both for pure diagonal (site) disorder, as
      well as for diagonal and off-diagonal (site and transfer) disorder. In both
      cases, large disorder leads to localization and destroys the characteristic phase
      space patterns of the WF found in the absence of disorder.

PMID- 17500683
TI  - Spectral theory of metastability and extinction in a branching-annihilation
      reaction.
AB  - We apply the spectral method, recently developed by the authors, to calculate the
      statistics of a reaction-limited multistep birth-death process, or chemical
      reaction, that includes as elementary steps branching A-->2A and annihilation 2A-
      >0 . The spectral method employs the generating function technique in conjunction
      with the Sturm-Liouville theory of linear differential operators. We focus on the
      limit when the branching rate is much higher than the annihilation rate and
      obtain accurate analytical results for the complete probability distribution
      (including large deviations) of the metastable long-lived state and for the
      extinction time statistics. The analytical results are in very good agreement
      with numerical calculations. Furthermore, we use this example to settle the issue
      of the "lacking" boundary condition in the spectral formulation.

PMID- 17500684
TI  - Mitigating the effects of measurement noise on Granger causality.
AB  - Computing Granger causal relations among bivariate experimentally observed time
      series has received increasing attention over the past few years. Such causal
      relations, if correctly estimated, can yield significant insights into the
      dynamical organization of the system being investigated. Since experimental
      measurements are inevitably contaminated by noise, it is thus important to
      understand the effects of such noise on Granger causality estimation. The first
      goal of this paper is to provide an analytical and numerical analysis of this
      problem. Specifically, we show that, due to noise contamination, (1) spurious
      causality between two measured variables can arise and (2) true causality can be
      suppressed. The second goal of the paper is to provide a denoising strategy to
      mitigate this problem. Specifically, we propose a denoising algorithm based on
      the combined use of the Kalman filter theory and the expectation-maximization
      algorithm. Numerical examples are used to demonstrate the effectiveness of the
      denoising approach.

PMID- 17500685
TI  - Evaluation of the permutational structure of quantum gases at finite temperature.
AB  - Proposed is an alternative method for permutational sampling in quantum gases
      using the path integral formulation of statistical mechanics. It is shown that in
      principle we are able to use two operators which enable us to construct a Markov
      chain through a graph of the irreducible representation of the symmetric group.
      As an illustration of this method, a test calculation of four particles in a
      harmonic trap is performed.

PMID- 17500686
TI  - Transport in a highly asymmetric binary fluid mixture.
AB  - We present molecular dynamics calculations of the thermal conductivity and
      viscosities of a model colloidal suspension with colloidal particles roughly one
      order of magnitude larger than the suspending liquid molecules. The results are
      compared with estimates based on the Enskog transport theory and effective medium
      theories (EMT) for thermal and viscous transport. We find, in particular, that
      EMT remains well applicable for predicting both the shear viscosity and thermal
      conductivity of such suspensions when the colloidal particles have a "typical"
      mass, i.e., much larger than the liquid molecules. Very light colloidal particles
      on the other hand yield higher thermal conductivities, in disagreement with EMT.
      We also discuss the consequences of these results for some proposed mechanisms
      for thermal conduction in nanocolloidal suspensions.

PMID- 17500687
TI  - Radial and axial segregation of granular matter in a rotating cylinder: a
      simulation study.
AB  - The phenomena of radial and axial segregation in a horizontal rotating cylinder
      containing a mixture of granular particles of two different species have been
      modeled using discrete particle simulation. Space-time plots and detailed imagery
      provide a comprehensive description of what occurs in the system. As is the case
      experimentally, the nature of the segregation depends on the parameters defining
      the problem; the radial component of the segregation may be transient or long
      lasting, and the axial component may or may not develop. Simulations displaying
      the different kinds of behavior are described and the particle dynamics
      associated with the axially segregated state examined. The importance of an
      appropriate choice of interaction for representing the effective friction force
      is demonstrated.

PMID- 17500688
TI  - Velocity distributions and aging in a cooling granular gas.
AB  - We use large-scale molecular dynamics simulations to study freely evolving
      granular gases with dimensionality d=2,3 . The system dissipates kinetic energy
      (or cools) due to inelastic collisions between granular particles. The density
      and velocity fields are approximately homogeneous at early times, and the system
      is said to be in a homogeneous cooling state (HCS). However, fluctuations in the
      density and velocity fields grow, and the system evolves into an inhomogeneous
      cooling state (ICS). We study the nature of velocity distributions in both the
      HCS and ICS. We also investigate the aging property of the velocity
      autocorrelation function.

PMID- 17500689
TI  - Uphill solitary waves in granular flows.
AB  - We have experimentally observed uphill solitary waves in the surface flow on a
      granular material. A heap is constructed by injecting sand between two vertical
      glass plates separated by a distance much larger than the average grain size,
      with an open boundary. As the heap reaches the open boundary, solitary
      fluctuations appear on the flowing layer and move "up the hill" (i.e., against
      the direction of the flow). We explain the phenomenon in the context of stop-and
      go traffic models.

PMID- 17500690
TI  - Dry and wet granular shock waves.
AB  - The formation of a shock wave in one-dimensional granular gases is considered,
      for both the dry and the wet cases, and the results are compared with the
      analytical shock wave solution in a sticky gas. Numerical simulations show that
      the behavior of the shock wave in both cases tends asymptotically to the sticky
      limit. In the inelastic gas (dry case) there is a very close correspondence to
      the sticky gas, with one big cluster growing in the center of the shock wave, and
      a step-like stationary velocity profile. In the wet case, the shock wave has a
      nonzero width which is marked by two symmetric heavy clusters performing
      breathing oscillations with slowly increasing amplitude. All three models have
      the same asymptotic energy dissipation law, which is important in the context of
      the free cooling scenario. For the early stage of the shock formation and
      asymptotic oscillations we provide analytical results as well.

PMID- 17500691
TI  - Velocity correlations in dense granular shear flows: effects on energy
      dissipation and normal stress.
AB  - We study the effect of precollisional velocity correlations on granular shear
      flow by molecular dynamics simulations of an inelastic hard sphere system.
      Comparison of the simulations with kinetic theory reveals that the theory
      overestimates both the energy dissipation rate and the normal stress in the dense
      flow region. We find that the relative normal velocity of colliding particles is
      smaller than that expected from random collisions, and the discrepancies in the
      dissipation and the normal stress can be adjusted by introducing the idea of the
      collisional temperature, from which we conclude that the velocity correlation
      neglected in the kinetic theory is responsible for the discrepancies. Our
      analysis of the distributions of the precollisional velocity suggests that the
      correlation grows through multiple inelastic collisions during the time scale of
      the inverse of the shear rate. As for the shear stress, the discrepancy is also
      found in the dense region, but it depends strongly on the particle inelasticity.

PMID- 17500692
TI  - Types of gas fluidization of cohesive granular materials.
AB  - Some years ago it was shown that gas-fluidized powders may transit from solid
      like to fluid-like fluidization prior to bubbling, shedding light on a long
      standing controversy on the nature of "homogeneous" fluidization. In this paper
      it is shown that some gas-fluidized powders may also transit from the fluid-like
      regime to elutriation, with full suppression of the bubbling regime. We provide a
      diagram that can be used to predict these types of fluidization exhibited by
      cohesive powders based on simple phenomenological equations in which particle
      aggregation due to attractive forces is a key ingredient.

PMID- 17500693
TI  - Role of interparticle forces and interparticle friction on the bulk friction in
      charged granular media subjected to shearing.
AB  - We study the consequences of the interplay between electrostatic forces,
      mechanical contact forces, and frictional properties of grains upon the bulk
      frictional properties of charged granular media subjected to quasistatic
      shearing. We show that, the variations in short-range electrostatic forces
      between the grains (which are often ignored in the existing studies) dominantly
      affect the bulk friction. Charging enhances the fabric anisotropy of heavily
      loaded contacts--this enhances the bulk friction, more significantly, in the case
      of low frictional granular systems.

PMID- 17500694
TI  - Influences of the interstitial liquid on segregation patterns of granular
      slurries in a rotating drum.
AB  - Granular mixtures immersed in a liquid (slurries) show segregation dynamics which
      are quantitatively and qualitatively different from those of dry systems. The
      principal mechanisms of the segregation dynamics in slurries, as well as the
      relevant material parameters that must be taken into account in a dynamic
      description are not sufficiently understood so far. We investigate experimentally
      the influence of the viscosity of the interstitial liquid on the coarsening of
      axial segregation patterns in a horizontally rotating mixer. It is found that not
      only the characteristic time scales but also fundamental structural features of
      these patterns are influenced by the viscous properties of the liquid component.

PMID- 17500695
TI  - Aging in attraction-driven colloidal glasses.
AB  - Aging in an attraction-driven colloidal glass is studied by computer simulations.
      The system is equilibrated without attraction and instantaneously "quenched," at
      constant colloid volume fraction, to one of two states beyond the glass
      transition; one is close to the transition, and the other one deep in the glass.
      The evolution of structural properties shows that bonds form in the system,
      increasing the local density, creating density deficits (holes) elsewhere. This
      process slows down with the time elapsed since the quench. As a consequence of
      bond formation, there is a slowing down of the dynamics, as measured by the mean
      squared displacement and the density, bond, and environment correlation
      functions. The density correlations can be time rescaled to collapse their long
      time (structural) decay. The time scale for structural relaxation shows for both
      quenches a superlinear dependence on waiting time; it grows faster than the bond
      lifetime, showing the collective origin of the transition. At long waiting times
      and high attraction strength, we observe arrested dynamics for more than three
      decades in time, although individual bonds are not permanent on this time scale.
      The localization length decreases as the state moves deeper in the glass; the
      nonergodicity parameter oscillates in phase with the structure factor. Our main
      results are obtained for systems with a barrier in the pair potential that
      inhibits phase separation. However, when this barrier is removed for the case of
      a deep quench, we find changes in the static structure but almost none in the
      dynamics. Hence our results for the aging behavior remain relevant to experiments
      in which the glass transition competes with phase separation.

PMID- 17500696
TI  - Frank's constant in the hexatic phase.
AB  - Using videomicroscopy data of a two-dimensional colloidal system the bond-order
      correlation function G{6} is calculated and used to determine both the
      orientational correlation length xi{6} in the liquid phase and the modulus of
      orientational stiffness, Frank's constant F{A}, in the hexatic phase. The latter
      is an anisotropic fluid phase between the crystalline and the isotropic liquid
      phase. F{A} is found to be finite within the hexatic phase, takes the value 72/pi
      at the hexatic<-->isotropic liquid phase transition, and diverges at the hexatic<
      ->crystal transition as predicted by the Kosterlitz-Thouless-Halperin-Nelson
      Young theory. This is a quantitative test of the mechanism of breaking the
      orientational symmetry by disclination unbinding.

PMID- 17500697
TI  - Synthetic diamond and wurtzite structures self-assemble with isotropic pair
      interactions.
AB  - Using inverse statistical-mechanical optimization techniques, we have discovered
      isotropic pair interaction potentials with strongly repulsive cores that cause
      the tetrahedrally coordinated diamond and wurtzite lattices to stabilize, as
      evidenced by lattice sums, phonon spectra, positive-energy defects, and self
      assembly in classical molecular dynamics simulations. These results challenge
      conventional thinking that such open lattices can only be created via directional
      covalent interactions observed in nature. Thus, our discovery adds to fundamental
      understanding of the nature of the solid state by showing that isotropic
      interactions enable the self-assembly of open crystal structures with a broader
      range of coordination number than previously thought. Our work is important
      technologically because of its direct relevance generally to the science of self
      assembly and specifically to photonic crystal fabrication.

PMID- 17500698
TI  - Counterion release and interaction of oppositely charged surfaces.
AB  - The interaction of two oppositely highly charged surfaces in an electrolyte
      solution and the number of released counterions from the slit between the
      surfaces were studied in terms of the anisotropic hypernetted chain and nonlinear
      Poisson-Boltzmann theories. Liquid theory predictions of the attractive pressure
      and release of counterions between the plates are larger than those of the mean
      field approach at low and moderate concentration of added salt. Further, at high
      salt concentration there is an opposite relationship of the two theories in their
      numerical results for the attractive pressure for all surface separations. These
      deviations of the predicted equilibrium properties arise both from the charge
      density and the ion size correlation effects included in hypernetted chain
      theory.

PMID- 17500699
TI  - Charging mechanism in colloidal particles leading to a linear relation between
      charge and size.
AB  - Colloidal particles that are dissolved in a liquid can become charged by
      preferential adsorption or dissociation of surface molecules. The assumption of a
      constant surface charge density leads to a particle charge that is proportional
      to the square of the radius. Recent experiments however have shown that in a
      number of cases the charge is linearly proportional to its size. We present a
      simple model for the charging of colloidal particles leading to a linear relation
      between charge and size in the framework of the mean-field Poisson-Boltzmann
      theory. The model is based on preferential adsorption or dissociation of surface
      molecules, in combination with a large concentration of chargeable surface sites.
      The model also predicts a surface potential that is independent of the particle
      size. Numerical simulations show that this model is in good agreement with
      analytical approximations.

PMID- 17500700
TI  - Shear-induced crystallization in jammed systems.
AB  - Simulations are used to address the effects of oscillating shear strain on jammed
      systems composed of spherical particles. The simulations show that shear
      oscillations with amplitudes of more than a few percent lead to substantial
      crystallization of the system. To ensure that the conclusions are independent of
      the simulation methodology, a range of simulations are carried out that use both
      molecular dynamics and athermal dynamics methods, soft and hard potentials,
      potentials with and without attractive forces, and systems with and without
      surrounding walls. The extent of crystallization is monitored primarily by the
      Q(6) order parameter, but also in some simulations by the potential energy and
      the radial distribution function, and by direct visual inspection. A mechanism is
      proposed for shear-induced crystallization of jammed systems, based on fold
      catastrophes of the free-energy landscape.

PMID- 17500701
TI  - Glass phenomenology from the connection to spin glasses.
AB  - Typical features of glass phenomenology such as the Vogel-Fulcher law, the
      Kauzmann paradox, and the Adam-Gibbs relationship are shown to follow from the
      recently discovered mapping of glasses to Ising spin glasses in a magnetic field.
      There seems to be sufficient universality near the glass transition temperature
      T{g} such that study of the spin-glass system can provide semiquantitative
      results for supercooled liquids.

PMID- 17500702
TI  - Mode-coupling theory for the slow collective dynamics of fluids adsorbed in
      disordered porous media.
AB  - We derive a mode-coupling theory for the slow dynamics of fluids confined in
      disordered porous media represented by spherical particles randomly placed in
      space. Its equations display the usual nonlinear structure met in this
      theoretical framework, except for a linear contribution to the memory kernel
      which adds to the usual quadratic term. The coupling coefficients involve
      structural quantities which are specific of fluids evolving in random
      environments and have expressions which are consistent with those found in
      related problems. Numerical solutions for two simple models with pure hard core
      interactions lead to the prediction of a variety of glass transition scenarios,
      which are either continuous or discontinuous and include the possibility of
      higher-order singularities and glass-glass transitions. The main features of the
      dynamics in the two most generic cases are reviewed and illustrated with detailed
      computations. Moreover, a reentry phenomenon is predicted in the low fluid-high
      matrix density regime and is interpreted as the signature of a de-correlation
      mechanism by fluid-fluid collisions competing with the localization effect of the
      solid matrix.

PMID- 17500703
TI  - Wetting and minimal surfaces.
AB  - We study minimal surfaces which arise in wetting and capillarity phenomena. Using
      conformal coordinates, we reduce the problem to a set of coupled boundary
      equations for the contact line of the fluid surface and then derive simple
      diagrammatic rules to calculate the nonlinear corrections to the Joanny-de Gennes
      energy. We argue that perturbation theory is quasilocal--i.e., that all geometric
      length scales of the fluid container decouple from the short-wavelength
      deformations of the contact line. This is illustrated by a calculation of the
      linearized interaction between contact lines on two opposite parallel walls. We
      present a simple algorithm to compute the minimal surface and its energy based on
      these ideas. We also point out the intriguing singularities that arise in the
      Legendre transformation from the pure Dirichlet to the mixed Dirichlet-Neumann
      problem.

PMID- 17500704
TI  - Spontaneous corrugation of dipolar membranes.
AB  - We present a simple model for dipolar elastic membranes that gives lattice-bound
      point dipoles complete orientational freedom as well as translational freedom
      along one coordinate (out of the plane of the membrane). There is an additional
      harmonic term which binds each of the dipoles to the six nearest neighbors on
      either triangular or distorted lattices. The translational freedom of the dipoles
      allows triangular lattices to find states that break out of the normal
      orientational disorder of frustrated configurations and which are stabilized by
      long-range antiferroelectric ordering. In order to break out of the frustrated
      states, the dipolar membranes form corrugated or "rippled" phases that make the
      lattices effectively nontriangular. We observe three common features of the
      corrugated dipolar membranes: (1) the corrugated phases develop easily when
      hosted on triangular lattices, (2) the wave vectors for the surface ripples are
      always found to be perpendicular to the dipole director axis, and (3) on
      triangular lattices, the dipole director axis is found to be parallel to any of
      the three equivalent lattice directions.

PMID- 17500705
TI  - Structure and stability of bent core liquid crystal fibers.
AB  - Recently it was found that fluid smectic phases of bent core liquid crystals
      formed freestanding fibers of extremely high slenderness ratios. Studies of these
      fibers showed that their structure was composed of concentric cylindrical smectic
      layers. For this configuration to be stable there must be an energy term that
      desires bending of the smectic layers. We show that an energy term that deals
      with the divergence of the dipolar direction can encourage layer bending if the
      layer chirality value is allowed to vary. The energy term associated with holding
      the layer chirality is closely related to layer compressions and electrical self
      interactions. For our model, we assumed a simple smectic-C geometry with constant
      molecular tilt and cone angle defined by the director with respect to the layer
      normal, but allowed a constant variation of the polar direction about the
      director. Applying this simplified model to a free energy which accounts for
      director distortions, divergence of the polar direction, biaxial layer strain,
      surface tension, and electrical self-interactions, we were able to show
      consistency between the stable fiber radius and other properties predicted in our
      model to results from experimental studies.

PMID- 17500706
TI  - Air tube formation at the freezing transition in nematic liquid crystals.
AB  - A phenomenon is presented, which changes the shape of gas bubbles in liquid
      crystals and also creates long gas tubes. The system consists of air bubbles
      which are injected into a nematic liquid crystal host. The shape of these air
      bubbles changes from spherical to ellipsoidal by initiating freezing of the
      sample. Furthermore, long gas tubes are formed from the air which was formerly
      dissolved in the liquid crystal. The gas tubes are created by the progression of
      the crystalline-liquid interface. Their length can reach up to 40 times their
      diameter. The diameter of the tubes depends on the pressure applied to the
      system, as well as on the interface velocity.

PMID- 17500707
TI  - Photoinduction of optical anisotropy in an azobenzene-containing ionic self
      assembly liquid-crystalline material.
AB  - Liquid-crystalline (LC) phase behavior and photoinduction of optical anisotropy
      in the ionic self-assembly complex 4-(4-diethylaminophenylazo) benzenesulfonate
      dimethyldidodecylammonium (EO-C12D) has been investigated by polarized light
      microscopy, differential scanning calorimetry (DSC), x-ray scattering, null
      ellipsometry, and UV-visible absorbance techniques. The complex exists in a
      bilayer smectic- A (smA{2}) LC phase at elevated temperatures (65-160 degrees C)
      and in a rectangular columnar (Col{r}) LC phase in the temperature range of -5-65
      degrees C . Hysteresis in the transition from the smectic to the columnar LC
      phase was observed. Detailed experimental investigations of the phase behavior,
      film-forming properties, and induction of optical anisotropy were performed. High
      values of photoinduced anisotropy (dichroic ratio of approximately 50) were
      detected when thin films of the complex were irradiated with linearly polarized
      light ( Ar+ laser, lambda=488 nm ). It was shown that the azobenzene units align
      perpendicular to the polarization of the exciting light causing an alignment of
      the columns parallel to the light electric field vector. On the basis of all
      experimental results a model of the photoinduced alignment of the photochromic
      complex is proposed in which photoalignment of the material is connected to the
      reorientation of domains.

PMID- 17500708
TI  - Quasi-two-dimensional Ising critical behavior of de Vries liquid crystals
      observed in the heat capacity and dielectric response.
AB  - Heat capacity and dielectric measurements have been made on a liquid crystal
      compound exhibiting de Vries type of smectic-A{*} (Sm-A{*}) phase. Heat capacity
      shows a significant anomaly which is almost symmetric for above and below the Sm
      A{*}-Sm-C{*} transition temperature. The transition was found to be very weakly
      first order. The critical exponent gamma determined from the dielectric data lies
      1.8+/-0.2. The present heat capacity data as well as former data for another
      compound of de Vries type have been analyzed in detail. It was found that the
      heat capacity data for both compounds are fitted well with a logarithmic
      divergence except in the immediate vicinity of the transition. These results
      agree with an expectation that de Vries Sm-A{*}-Sm-C-{*} transition can exhibit
      quasi-two-dimensional Ising critical behavior.

PMID- 17500709
TI  - Smectic liquid crystals in an anisotropic random environment.
AB  - We report a high-resolution x-ray scattering study of the smectic liquid crystal
      octylcyanobiphenyl (8CB) confined to aligned colloidal aerosil gels. The aligned
      gels introduce orientational fields that promote long-range nematic order while
      imposing positional random fields that couple to the smectic density wave and
      disrupt the formation of an ordered smectic phase. At low densities of aerosil,
      the low-temperature scattering intensity is consistent with the presence of a
      topologically ordered XY Bragg glass phase that is predicted to form in response
      to such anisotropic quenched disorder. The observed features of the phase include
      an algebraic decay of the smectic correlations, which is truncated at large
      length scales due to the imperfect nematic order, and a power-law exponent that
      agrees closely with the universal value predicted for the XY Bragg glass. At
      higher aerosil densities, deviations from the XY Bragg glass form are apparent.
      At high temperature, the scattering intensity displays pretransitional dynamic
      fluctuations associated with the destroyed nematic to smectic-A transition. The
      fluctuations obey quasicritical behavior over an extended range of reduced
      temperature. The effective critical exponents for the correlation lengths and
      smectic susceptibility differ systematically from those of pure 8CB, indicating
      that coupling of the nematic order to the gel suppresses its role in the smectic
      critical behavior.

PMID- 17500710
TI  - Rearrangement of topological defects and anchoring on the inclusion boundary in
      ferroelectric smectic membranes.
AB  - We report experiments on a ferroelectric membrane and droplets with tunable
      surface properties. In smectic membranes the configuration of the c -director
      field near inclusions may be rearranged drastically with temperature. The
      transformation of the c -director field results from the competition between the
      elastic and polar properties of the membranes. We demonstrate that anchoring
      conditions on the inclusion boundary are not fixed but depend on the temperature.
      A dipolar c -director configuration near droplets can evolve to a mixed
      configuration and to a quadrupolar one. These modifications of the c -director
      field near the inclusions lead to a change of the interaction between the
      inclusions, their self-organization, and even to the destruction of structures
      already formed by the inclusions. Our observations open new possibilities for
      manipulating inclusions and controlling their self-organization.

PMID- 17500711
TI  - Nuclear magnetic resonance parameters of atomic xenon dissolved in Gay-Berne
      model liquid crystal.
AB  - We present constant-pressure Monte Carlo simulations of nuclear magnetic
      resonance (NMR) spectral parameters, nuclear magnetic shielding relative to the
      free atom as well as nuclear quadrupole coupling, for atomic xenon dissolved in a
      model thermotropic liquid crystal. The solvent is described by Gay-Berne (GB)
      molecules with parametrization kappa=4.4, kappa{'}=20.0 , and mu=nu=1 . The
      reduced pressure of P{*}=2.0 is used. Previous simulations of a pure GB system
      with this parametrization have shown that upon lowering the temperature, the
      model exhibits isotropic, nematic, smectic- A , and smectic- B /molecular crystal
      phases. We introduce spherical xenon solutes and adjust the energy and length
      scales of the GB-Xe interaction to those of the GB-GB interaction. This is done
      through first principles quantum chemical calculations carried out for a dimer of
      model mesogens as well as the mesogen-xenon complex. We preparametrize quantum
      chemically the Xe nuclear shielding and quadrupole coupling tensors when
      interacting with the model mesogen, and use the parametrization in a pairwise
      additive fashion in the analysis of the simulation. We present the temperature
      evolution of {129/131}Xe shielding and 131Xe quadrupole coupling in the different
      phases of the GB model. From the simulations, separate isotropic and anisotropic
      contributions to the experimentally available total shielding can be obtained. At
      the experimentally relevant concentration, the presence of the xenon atoms does
      not significantly affect the phase behavior as compared to the pure GB model. The
      simulations reproduce many of the characteristic experimental features of Xe NMR
      in real thermotropic LCs: Discontinuity in the value or trends of the shielding
      and quadrupole coupling at the nematic-isotropic and smectic-A-nematic phase
      transitions, nonlinear shift evolution in the nematic phase reflecting the
      behavior of the orientational order parameter, and decreasing shift in the
      smectic-A phase. The last observation is due to the preference of the xenon
      solutes to occupy the interlayer space where the density of the medium is reduced
      as compared to the layers. There are systematic deviations, however, in the
      magnitude of the shielding and its discontinuities, as well as the distribution
      of the solutes in the translationally ordered smectic-A phase, between the
      simulation and experiment. These deficiencies are believed to result from the
      lack of flexibility of the GB model.

PMID- 17500712
TI  - Defect-enhanced nematic surface order reconstruction.
AB  - Within the Landau-de Gennes phenomenological theory, we study the influence of an
      applied electric field with average strength E{a} on the position of a nematic
      line defect with topological charge M=+/-1/2 in a hybrid cell. We explore the
      biaxial structure of the defect core and we describe its expulsion from the cell
      upon increasing E{a}. We show that prior to the expulsion the defect core
      displays dramatic changes for strong enough surface anchorings. At a critical
      value of E{a}, the core broadens and merges into a surface layer with a large
      biaxiality. This transition corresponds to the reconstruction of the nematic
      order already observed in the bulk in response to an applied electric field. A
      similar order reconstruction could take place even in the absence of defects, but
      at a higher threshold.

PMID- 17500713
TI  - Statistical theory of the flexoelectric polarization for the uniaxial nematic
      phase.
AB  - A statistical theory for the dipole flexoelectric (FE) polarization in liquid
      crystals is derived in the thermodynamic limit at small distortions and a small
      density. General microscopic expressions for the FE coefficients are rederived in
      the case of the uniaxial nematic phase. The expressions involve the one-particle
      distribution function and the potential energy of two-body short-range
      interactions. It is shown that, for wedge-shaped polar molecules, the FE
      coefficients are proportional to the longitudinal component of the molecule
      dipole moment. The FE coefficients include a term linear in P{2} and a quadratic
      form in P{j} (j-even). The theory is used to calculate the temperature dependence
      of the elastic constants and the FE coefficients for a system of rigid molecules
      similar to cones.

PMID- 17500714
TI  - Kinetics of the thermal back relaxation time of the photoinduced nematic
      isotropic transition.
AB  - We report on the temperature dependence of the response time for the
      photochemical and thermal back relaxation processes observed in a material
      exhibiting a photostimulated, isothermal nematic-isotropic phase transition. It
      is found that the time required for the system to achieve the photostationary
      state as well as to recover the original state after photoirradiation with a uv
      beam is a smooth function of the absolute temperature of the sample, except in
      the vicinity of the transition. The duration of the recovery can be split into
      two parts: delay time and response time. Using a simple description based on the
      Maier-Saupe model, we show that the temperature dependence of the response time
      can be understood in terms of the order parameter excess between the equilibrium
      and photostimulated states.

PMID- 17500715
TI  - Dynamics of smectic elastomers.
AB  - We study the low-frequency, long-wavelength dynamics of liquid crystal
      elastomers, crosslinked in the smectic-A phase, in their smectic-A, biaxial
      smectic and smectic-C phases. Two different yet related formulations are
      employed. One formulation describes the pure hydrodynamics and does not
      explicitly involve the Frank director, which relaxes to its local equilibrium
      value in a nonhydrodynamic time. The other formulation explicitly treats the
      director and applies beyond the hydrodynamic limit. We compare the low-frequency,
      long-wavelength dynamics of smectic-A elastomers to that of nematics and show
      that the two are closely related. For the biaxial smectic and the smectic-C
      phases, we calculate sound velocities and the mode structure in certain symmetry
      directions. For the smectic-C elastomers, in addition, we discuss in some detail
      their possible behavior in rheology experiments.

PMID- 17500716
TI  - Stiff knots.
AB  - We report on the geometry and mechanics of knotted stiff strings. We discuss both
      closed and open knots. Our two main results are that (i) their equilibrium energy
      as well as the equilibrium tension for open knots depends on the type of knot as
      the square of the bridge number and (ii) braid localization is found to be a
      general feature of stiff string entanglements, while angle and knot localizations
      are forbidden. Moreover, we identify a family of knots for which the equilibrium
      shape is a circular braid. Two other equilibrium shapes are found from Monte
      Carlo simulations. These three shapes are confirmed by rudimentary experiments.
      Our approach is also extended to the problem of the minimization of the length of
      a knotted string with a maximum allowed curvature.

PMID- 17500717
TI  - Self-consistent field theory simulations of block copolymer assembly on a sphere.
AB  - Recently there has been a strong interest in the area of defect formation in
      ordered structures on curved surfaces. Here we explore the closely related topic
      of self-assembly in thin block copolymer melt films confined to the surface of a
      sphere. Our study is based on a self-consistent field theory (SCFT) model of
      block copolymers that is numerically simulated by spectral collocation with a
      spherical harmonic basis and an extension of the Rasmussen-Kalosakas operator
      splitting algorithm [J. Polym. Sci. Part B: Polym. Phys. 40, 1777 (2002)]. In
      this model, we assume that the composition of the thin block copolymer film
      varies only in longitude and colatitude and is constant in the radial direction.
      Using this approach we are able to study the formation of defects in the lamellar
      and cylindrical phases, and their dependence on sphere radius. Specifically, we
      compute ground-state (i.e., lowest-energy) configurations on the sphere for both
      the cylindrical and lamellar phases. Grain boundary scars are also observed in
      our simulations of the cylindrical phase when the sphere radius surpasses a
      threshold value R_{c} approximately 5d , where d is the natural lattice spacing
      of the cylindrical phase, which is consistent with theoretical predictions
      [Bowick, Phys. Rev. B 62, 8738 (2000); Bausch, Science 299, 1716 (2003)]. A
      strong segregation limit approximate free energy is also presented, along with
      simple microdomain packing arguments, to shed light on the observed SCFT
      simulation results.

PMID- 17500718
TI  - Calculation of local mechanical properties of filled polymers.
AB  - A study is presented on the effects of smooth nanoparticles on the structure and
      elastic moduli of a polymer matrix. Structural changes between the unfilled
      polymer matrix and the nanocomposite give rise to the formation of a glassy layer
      that surrounds the nanoparticles. Results for the effects of particle size and
      concentration on the local and overall mechanical properties of the polymer are
      consistent with experimental macroscopic observations. At the molecular level, it
      is found that dispersed, attractive nanoparticles alter the nonaffine
      displacement fields that arise in the polymer glass upon deformation, thereby
      rendering the nanocomposite glass less fragile.

PMID- 17500719
TI  - Molecular dynamics study of crystallization of polymer systems confined in small
      nanodomains.
AB  - We study the ordering dynamics of polymer crystallization using molecular
      dynamics simulations, in which the polymers are confined to small nanodomains
      surrounded by a noncrystalline medium. Although the adsorption process and
      surface diffusion of polymer chains play a major role in the case of the
      crystalline interface, the domain interface which consists of noncrystalline
      medium does not have such a crystal substrate to induce the growth of a crystal
      layer, which may lead to different ordering dynamics. We found that existence of
      a noncrystalline domain interface has two opposite effects. In the case of
      semiflexible polymer systems, the domain interface accelerates crystallization in
      the initial period, whereas it suppresses crystallization in the intermediate or
      late period. When the rigidity of polymer chains increases, the acceleration
      effect of the initial crystallization induced by the domain interface is
      sometimes hidden by spontaneous homogeneous nucleation. These ordering behaviors
      can be explained by the restriction on the local chain direction near the domain
      surface in the crystal nucleation stage and the restriction of large orientation
      relaxation and coalescence in the crystal growth stage. Simulation results reveal
      that the confinement by the noncrystalline medium does not have a simple effect
      on the polymer crystallization dynamics, but has various conflicting effects
      combined with the time stage, the rigidity of polymer chains, and the strength of
      the surrounding domain interface.

PMID- 17500720
TI  - Nonlinear finite-element analysis of nanoindentation of viral capsids.
AB  - Recent atomic force microscope (AFM) nanoindentation experiments measuring
      mechanical response of the protein shells of viruses have provided a quantitative
      description of their strength and elasticity. To better understand and interpret
      these measurements, and to elucidate the underlying mechanisms, this paper adopts
      a course-grained modeling approach within the framework of three-dimensional
      nonlinear continuum elasticity. Homogeneous, isotropic, elastic, thick-shell
      models are proposed for two capsids: the spherical cowpea chlorotic mottle virus
      (CCMV), and the ellipsocylindrical bacteriophage phi29 . As analyzed by the
      finite-element method, these models enable parametric characterization of the
      effects of AFM tip geometry, capsid dimensions, and capsid constitutive
      descriptions. The generally nonlinear force response of capsids to indentation is
      shown to be insensitive to constitutive particulars, and greatly influenced by
      geometric and kinematic details. Nonlinear stiffening and softening of the force
      response is dependent on the AFM tip dimensions and shell thickness. Fits of the
      models capture the roughly linear behavior observed in experimental measurements
      and result in estimates of Young's moduli of approximately 280-360 MPa for CCMV
      and approximately 4.5 GPa for phi29 .

PMID- 17500721
TI  - Modeling fractal-like drug elimination kinetics using an interacting random-walk
      model.
AB  - We introduce an interacting random-walk model to describe the residence time of
      drug molecules undergoing a series of sojourn times in the body before being
      permanently eliminated under either homogeneous or heterogeneous conditions. We
      show that short-term correlations between drug molecules lead to Michaelis-Menten
      kinetics while long-term correlations lead to transient fractal-like kinetics. By
      combining both types of correlation, fractal-like Michaelis-Menten kinetics are
      achieved, and the simulations confirm previous analytical results.

PMID- 17500722
TI  - Wrapping conformations of a polymer on a curved surface.
AB  - The conformation of a polymer on a curved surface is high on the agenda for
      polymer science. We assume that the free energy of the system is the sum of
      bending energy of the polymer and the electrostatic attraction between the
      polymer and surface. As is also assumed, the polymer is very stiff with an
      invariant length for each segment so that we can neglect its tensile energy and
      view its length as a constant. Based on the principle of minimization of free
      energy, we apply a variation method with a locally undetermined Lagrange
      multiplier to obtain a set of equations for the polymer conformation in terms of
      local geometrical quantities. We have obtained some numerical solutions for the
      conformations of the polymer chain on cylindrical and ellipsoidal surfaces. With
      some boundary conditions, we find that the free energy profiles of polymer chains
      behave differently and depend on the geometry of the surface for both cases. In
      the former case, the free energy of each segment distributes within a narrower
      range and its value per unit length oscillates almost periodically in the
      azimuthal angle. However, in the latter case the free energy distributes in a
      wider range with larger value at both ends and smaller value in the middle of the
      chain. The structure of a polymer wrapping around an ellipsoidal surface is apt
      to dewrap a polymer from the endpoints. The dependence of threshold lengths for a
      polymer on the initially anchored positions is also investigated. With initial
      conditions, the threshold wrapping length is found to increase with the
      electrostatic attraction strength for the ellipsoidal surface case. When a
      polymer wraps around a sphere surface, the threshold length increases
      monotonically with the radius without the self-intersection configuration for a
      polymer. We also discuss potential applications of the present theory to
      DNA/protein complex and further researches on DNA on the curved surface.

PMID- 17500723
TI  - Necklace-cloverleaf transition in associating RNA-like diblock copolymers.
AB  - We consider a A{m}B{n} diblock copolymer, whose links are capable of forming
      local reversible bonds with each other. We assume that the resulting structure of
      the bonds is RNA like--i.e., topologically isomorphic to a tree. We show that,
      depending on the relative strengths of A-A , A-B , and B-B contacts, such a
      polymer can be in one of two different states. Namely, if a self-association is
      preferable (i.e., A-A and B-B bonds are comparatively stronger than A-B
      contacts), then the polymer forms a typical randomly branched cloverleaf
      structure with the so-called roughness exponent gamma = 1/2 . On the contrary, if
      alternating association is preferable (i.e., A-B bonds are stronger than A-A and
      B-B contacts), then the polymer tends to form a generally linear necklace
      structure with gamma = 1 . The transition between cloverleaf and necklace states
      is studied in detail, and it is shown that it is a second-order phase transition.

PMID- 17500724
TI  - Tension dynamics in semiflexible polymers. I. Coarse-grained equations of motion.
AB  - Based on the wormlike chain model, a coarse-grained description of the nonlinear
      dynamics of a weakly bending semiflexible polymer is developed. By means of a
      multiple-scale perturbation analysis, a length-scale separation inherent to the
      weakly bending limit is exploited to reveal the deterministic nature of the
      spatio temporal relaxation of the backbone tension and to deduce the
      corresponding coarse-grained equation of motion. From this partial integro
      differential equation, some detailed analytical predictions for the nonlinear
      response of a weakly bending polymer are derived in an accompanying paper [O.
      Hallatschek, following paper, Phys. Rev. E 75, 031906 (2007)].

PMID- 17500725
TI  - Tension dynamics in semiflexible polymers. II. Scaling solutions and
      applications.
AB  - In part I [O. Hallatschek, preceding paper, Phys. Rev. E 75, 031905 (2007)] of
      this contribution, a systematic coarse-grained description of the dynamics of a
      weakly bending semiflexible polymer was developed. Here, we discuss analytical
      solutions of the established deterministic partial integro-differential equation
      for the spatiotemporal relaxation of the backbone tension. For prototypal
      experimental situations, such as the sudden application or release of a strong
      external pulling force, it is demonstrated that the tensile dynamics reflects the
      self-affine conformational fluctuation spectrum in a variety of intermediate
      asymptotic power laws. Detailed and explicit analytical predictions for the
      tension propagation and relaxation and corresponding results for common
      observables, such as the end-to-end distance, are obtained.

PMID- 17500726
TI  - Compact dynamical model of brain activity.
AB  - A compact physiologically based mean-field formulation of brain dynamics is
      proposed to model observed brain activity and electroencephalographic (EEG)
      signals. In contrast to existing formulations, which are more detailed and
      complicated, our model is described by a single second-order delay differential
      equation that encapsulates salient aspects of the physiology. The model captures
      essential features of activity mediated by fast corticocortical connections and
      delayed feedbacks via extracortical pathways and external stimuli. In the linear
      regime, these features can be simply expressed by three coefficients derived from
      the properties of these physiological pathways and explicit nonlinear
      approximations are also derived. This compact model successfully reproduces the
      main features of experimental EEG's and the predictions of previous models,
      including resonance peaks in EEG spectra and nonlinear dynamics. As an
      illustration, key features of the dynamics of epileptic seizures are shown to be
      reproduced by the model. Due to its compact form, the model will facilitate
      insight into nonlinear brain dynamics via standard nonlinear techniques and will
      guide analysis and investigation of more complex models. It is thus a useful tool
      for analyzing complex brain activity, especially when it exhibits low-dimensional
      dynamics.

PMID- 17500727
TI  - Lateralization as a symmetry breaking process in bird song.
AB  - The singing by songbirds is a most convincing example in the animal kingdom of
      functional lateralization of the brain, a feature usually associated with human
      language. Lateralization is expressed as one or both of the bird's sound sources
      being active during the vocalization. Normal songs require high coordination
      between the vocal organ and respiratory activity, which is bilaterally symmetric.
      Moreover, the physical and neural substrate used to produce the song lack obvious
      asymmetries. In this work we show that complex spatiotemporal patterns of motor
      activity controlling airflow through the sound sources can be explained in terms
      of spontaneous symmetry breaking bifurcations. This analysis also provides a
      framework from which to study the effects of imperfections in the system's
      symmetries. A physical model of the avian vocal organ is used to generate
      synthetic sounds, which allows us to predict acoustical signatures of the song
      and compare the predictions of the model with experimental data.

PMID- 17500728
TI  - Model of hyphal tip growth involving microtubule-based transport.
AB  - We propose a simple model for mass transport within a fungal hypha and its
      subsequent growth. Inspired by the role of microtubule-transported vesicles, we
      embody the internal dynamics of mass inside a hypha with mutually excluding
      particles progressing stochastically along a growing one-dimensional lattice. The
      connection between long-range transport of materials for growth and the resulting
      extension of the hyphal tip has not previously been addressed in the modeling
      literature to our knowledge. We derive and analyze mean-field equations for the
      model and present a phase diagram of its steady-state behavior, which we compare
      to simulations. We discuss our results in the context of the filamentous fungus
      Neurospora crassa.

PMID- 17500729
TI  - Solutions of burnt-bridge models for molecular motor transport.
AB  - Transport of molecular motors, stimulated by interactions with specific links
      between consecutive binding sites (called "bridges"), is investigated
      theoretically by analyzing discrete-state stochastic "burnt-bridge" models. When
      an unbiased diffusing particle crosses the bridge, the link can be destroyed
      ("burned") with a probability p , creating a biased directed motion for the
      particle. It is shown that for probability of burning p=1 the system can be
      mapped into a one-dimensional single-particle hopping model along the periodic
      infinite lattice that allows one to calculate exactly all dynamic properties. For
      the general case of p<1 a theoretical method is developed and dynamic properties
      are computed explicitly. Discrete-time and continuous-time dynamics for periodic
      distribution of bridges and different burning dynamics are analyzed and compared.
      Analytical predictions are supported by extensive Monte Carlo computer
      simulations. Theoretical results are applied for analysis of the experiments on
      collagenase motor proteins.

PMID- 17500730
TI  - Dynamic stability in random and scale-free B-lymphocyte networks.
AB  - One of the most intriguing features of the immune system is regulation: a limited
      response when perturbed repeatedly. We propose a minimal network model for immune
      regulation in a lymphocyte network containing two types of elements: B
      lymphocytes and ligands that bind to their receptors. Effective interactions
      between B cells, mediated by other components of the immune system can be
      excitatory or inhibitory. In our model, B cell clones and ligand species are
      represented by nodes, and interactions by links. We expect that, as in many
      complex systems, the connectivity distribution is broad, motivating study of the
      model on a scale-free network; for comparison we study the same dynamics on a
      random graph. We characterize the dynamics of the model and its response to
      perturbations. Our model reproduces several key features of immune system
      dynamics: regulation (saturation of response), and more rapid response upon
      repeated perturbation with the same agents. Our results suggest that a scale-free
      network of interactions contributes to the regulation and dynamics of the immune
      system.

PMID- 17500731
TI  - Spike patterning of a stochastic phase model neuron given periodic inhibition.
AB  - We present a phase model of a repetitively firing neuron possessing a phase
      dependent stochastic response to periodic inhibition. We analyze the dynamics in
      terms of a stochastic phase map and determine the invariant phase distribution.
      We use the latter to compute both the distribution of interspike intervals (ISIs)
      and the stochastic winding number (mean firing rate) as a function of the input
      frequency. We show that only low-order phase locking persists in the presence of
      weak phase dependence, and is characterized statistically by a multimodal ISI
      distribution and a nonmonotonic variation in the stochastic winding number as a
      function of input frequency.

PMID- 17500732
TI  - Extended method of moments for deterministic analysis of stochastic multistable
      neurodynamical systems.
AB  - The analysis of transitions in stochastic neurodynamical systems is essential to
      understand the computational principles that underlie those perceptual and
      cognitive processes involving multistable phenomena, like decision making and
      bistable perception. To investigate the role of noise in a multistable
      neurodynamical system described by coupled differential equations, one usually
      considers numerical simulations, which are time consuming because of the need for
      sufficiently many trials to capture the statistics of the influence of the
      fluctuations on that system. An alternative analytical approach involves the
      derivation of deterministic differential equations for the moments of the
      distribution of the activity of the neuronal populations. However, the
      application of the method of moments is restricted by the assumption that the
      distribution of the state variables of the system takes on a unimodal Gaussian
      shape. We extend in this paper the classical moments method to the case of
      bimodal distribution of the state variables, such that a reduced system of
      deterministic coupled differential equations can be derived for the desired
      regime of multistability.

PMID- 17500733
TI  - Folding behavior of ribosomal protein S6 studied by modified Go-like model.
AB  - Recent experimental and theoretical studies suggest that, although topology is
      the determinant factor in protein folding, especially for small single-domain
      proteins, energetic factors also play an important role in the folding process.
      The ribosomal protein S6 has been subjected to intensive studies. A radical
      change of the transition state in its circular permutants has been observed,
      which is believed to be caused by a biased distribution of contact energies.
      Since the simplistic topology-only Go-like model is not able to reproduce such an
      observation, we modify the model by introducing variable contact energies between
      residues based on their physicochemical properties. The modified Go-like model
      can successfully reproduce the Phi-value distributions, folding nucleus, and
      folding pathways of both the wild-type and circular permutants of S6.
      Furthermore, by comparing the results of the modified and the simplistic models,
      we find that the hydrophobic effect constructs the major force that balances the
      loop entropies. This may indicate that nature maintains the folding cooperativity
      of this protein by carefully arranging the location of hydrophobic residues in
      the sequence. Our study reveals a strategy or mechanism used by nature to get out
      of the dilemma when the native structure, possibly required by biological
      function, conflicts with folding cooperativity. Finally, the possible
      relationship between such a design of nature and amyloidosis is also discussed.

PMID- 17500734
TI  - Dissociative electron attachment to hydrated single DNA strands.
AB  - The present experiments concern electron interactions with a film of short single
      strands of DNA covered by 3 monolayers of water, which corresponds to 5.25 water
      molecules per nucleotide. We report on the desorption of H{-}, O{-}, OH{-} from
      this target induced by 3-20 eV electrons. Below 15 eV, these anions emanate
      principally from a new type of dissociative core-excited transient anions formed
      via electron capture by a DNA- H2O complex. A smaller portion of the H{-}
      desorption signal arises from weakly bonded H2O molecules. The overall anion
      yield from DNA is increased by a factor of 1.6 owing to the presence of water.

PMID- 17500735
TI  - Inherent multistability in arrays of autoinducer coupled genetic oscillators.
AB  - Rhythm generation mechanisms are very important for genetic network functions as
      well as for the design of synthetic genetic circuits. A significant attention to
      date has been focused on the synchronization of communicating genetic units,
      which results in the production of an unified rhythm. In contrast to this we
      address the question: what mechanisms of intercell communication can be
      responsible for multirhythmicity in globally coupled genetic units? Here, we show
      that an autoinducer intercell communication system that provides coupling between
      synthetic genetic oscillators will inherently lead to multirhythmicity and the
      appearance of several coexisting dynamical regimes, if the time evolution of the
      genetic network can be split in two well-separated time scales. We investigate in
      detail a variety of dynamical regimes in a genetic population and show the
      possibility for multiple element distributions between clusters, as well as the
      possibility of generating complex oscillations with different return times in one
      limit cycle.

PMID- 17500736
TI  - Stochastic suppression of gene expression oscillators under intercell coupling.
AB  - This paper examines the dynamics of an ensemble of hysteresis-based genetic
      relaxation oscillators, focusing on the influence of noise and cell-to-cell
      coupling on the appearance of new dynamical regimes. In particular, we show that
      control of the coupling strength and noise can effectively change the dynamics of
      the system leading to behaviors such as clustering, synchronous and asynchronous
      oscillations, and suppression. Moreover, under certain conditions an optimal
      amount of noise can lead to increased order in the system. The results obtained
      are correlated with relevant biological processes that occur in living organisms.

PMID- 17500737
TI  - Solitary excitations in B-Z DNA transition: a theoretical and numerical study.
AB  - The molecular mechanism of B-Z DNA transition remains elusive since the
      elucidation of the left-handed Z-DNA structure using atomic resolution
      crystallographic study. Numerous proposals for the molecular mechanism have been
      advanced, but none has provided a satisfactory explanation for the process. A
      nonlinear DNA model is proposed which enables one to derive various hypothesized
      molecular mechanisms, namely the Harvey model, Zang and Olson model, and the
      stretched intermediate model, by imposing certain constraints and conditions on
      the model. These constraints raise the need to reevaluate experimental
      investigations on B-Z DNA transition.

PMID- 17500738
TI  - Measuring peptide mass spectrum correlation using the quantum Grover algorithm.
AB  - We investigated the use of the quantum Grover algorithm in the mass-spectrometry
      based protein identification process. The approach coded the mass spectra on a
      quantum register and uses the Grover search algorithm for searching multiple
      solutions to find matches from a database. Measurement of the fidelity between
      the input and final states was used to quantify the similarity between the
      experimental and theoretical spectra. The optimal number of iteration is proven
      to be pi/4sqrt[N/k] , where k refers to the number of marked states. We found
      that one iteration is sufficient for the search if we let more that 62% of the N
      states be marked states. By measuring the fidelity after only one iteration of
      Grover search, we discovered that it resembles that of the correlation-based
      measurement used in the existing protein identification software. We concluded
      that the quantum Grover algorithm can be adapted for a correlation-based mass
      spectra database search, provided that decoherence can be kept to a minimum.

PMID- 17500739
TI  - Interference of stochastic resonances: splitting of Kramers' rate.
AB  - We consider the escape of particles located in the middle well of a symmetric
      triple well potential driven sinusoidally by two forces such that the potential
      wells rock as in stochastic resonance and the height of the potential barrier
      oscillates symmetrically about a mean as in resonant activation. It has been
      shown that depending on their phase difference the application of these two
      synchronized signals may lead to a splitting of time averaged Kramers' escape
      rate and a preferential product distribution in a parallel chemical reaction in
      the steady state.

PMID- 17500740
TI  - Charged particle in a magnetic field: Jarzynski equality.
AB  - We describe some solvable models which illustrate the Jarzynski theorem and
      related fluctuation theorems. We consider a charged particle in the presence of a
      magnetic field in a two-dimensional harmonic well. In the first case the center
      of the harmonic potential is translated with a uniform velocity, while in the
      other case the particle is subjected to an ac force. We show that the Jarzynski
      identity complements the Bohr-van Leeuwen theorem on the absence of diamagnetism
      in an equilibrium classical system.

PMID- 17500741
TI  - Behavior of flowing granular materials under variable g.
AB  - We consider the impact of the effective gravitational acceleration g{eff} on
      gravity-driven granular shear flow utilizing a tumbler of radius R rotating at
      angular velocity omega when g{eff} is varied up to 25 times the gravitational
      level on Earth in a large centrifuge. The Froude number Fr=omega{2}R/g{eff} is
      shown to be the proper scaling to characterize the effect of gravity on the angle
      of repose of the flowing layer. Likewise, transitions between flow regimes depend
      on Fr. Furthermore, the thickness of the flowing layer is independent of the g
      level. These results provide a starting point for understanding granular flows on
      planetary bodies with g{eff} different than on Earth for application to planetary
      exploration and formation of geologic features.

PMID- 17500742
TI  - Birefringence determination in turbid media.
AB  - We study the influence of birefringence on incoherent polarized light transport
      in turbid media. In particular, Mueller matrices backscattered by a diffusing
      medium are modified by the birefringence of the suspending phase. We study this
      effect both theoretically, through Monte Carlo simulations, and experimentally
      with a highly birefringent xanthane solution in which particles are added at
      various concentrations to modify its turbidity. Comparisons between experiments
      on flow-induced birefringence of the xanthane solution with or without particles
      are in good agreement and show the capability of measuring birefringence in
      turbid media through analysis of Mueller matrices.

PMID- 17500743
TI  - Excitable Greenberg-Hastings cellular automaton model on scale-free networks.
AB  - We study the excitable Greenberg-Hastings cellular automaton model on scale-free
      networks. We obtain analytical expressions for no external stimulus the uncoupled
      case. It is found that the curves, the average activity F versus the external
      stimulus rate r, can be fitted by a Hill function, but not exactly, there exists
      a relation F approximately r{alpha} for the low-stimulus response, where the
      Stevens-Hill exponent alpha ranges from alpha=1 in the subcritical regime to
      alpha=0.5 at criticality. At the critical point, the range is maximal, but not
      divergent. We also calculate the average activity F{k}(r) and the dynamic range
      Delta{k}(p) for nodes with given connectivity k. It is interesting that nodes
      with larger connectivity have larger optimal range, which could be applied in
      biological experiments to reveal the network topology.

PMID- 17500744
TI  - Bifractality of human DNA strand-asymmetry profiles results from transcription.
AB  - We use the wavelet transform modulus maxima method to investigate the
      multifractal properties of strand-asymmetry DNA walk profiles in the human
      genome. This study reveals the bifractal nature of these profiles, which involve
      two competing scale-invariant (up to repeat-masked distances less, or similar 40
      kbp) components characterized by Holder exponents h{1}=0.78 and h{2}=1,
      respectively. The former corresponds to the long-range-correlated homogeneous
      fluctuations previously observed in DNA walks generated with structural codings.
      The latter is associated with the presence of jumps in the original strand
      asymmetry noisy signal S. We show that a majority of upward (downward) jumps co
      locate with gene transcription start (end) sites. Here 7228 human gene
      transcription start sites from the refGene database are found within 2 kbp from
      an upward jump of amplitude DeltaS > or = 0.1 which suggests that about 36% of
      annotated human genes present significant transcription-induced strand asymmetry
      and very likely high expression rate.

PMID- 17500745
TI  - Identifying characteristic scales in the human genome.
AB  - The scale-free, long-range correlations detected in DNA sequences contrast with
      characteristic lengths of genomic elements, being particularly incompatible with
      the isochores (long, homogeneous DNA segments). By computing the local behavior
      of the scaling exponent alpha of detrended fluctuation analysis (DFA), we
      discriminate between sequences with and without true scaling, and we find that no
      single scaling exists in the human genome. Instead, human chromosomes show a
      common compositional structure with two characteristic scales, the large one
      corresponding to the isochores and the other to small and medium scale genomic
      elements.

PMID- 17500746
TI  - Vortex formation in swarms of interacting particles.
AB  - Vortexlike swarming behavior is observed in a wide range of biological systems.
      In the work reported here a discrete particle model is used to investigate the
      onset of such vortexlike behavior in a swarm of interacting particles. A
      constrained minimization of the total effective energy of the swarm of particles
      is performed, with the total angular momentum of the swarm conserved. It is shown
      that the emergence of vortexlike behavior can then be viewed as a constrained
      minimum energy configuration which the swarm relaxes into.

PMID- 17500747
TI  - Experimental observation of different types of chaotic synchronization in an
      electrochemical cell.
AB  - Chaotic synchronization for a pair of electrochemical oscillators is studied
      experimentally. The underlying bidirectional coupling between the two oscillators
      is achieved by immersing the two anodes in a common electrolytic solution. The
      horizontal distance between these two electrodes determines the strength of the
      coupling constant. On monotonically decreasing the distance between the two
      anodes, different domains of chaotic synchronization, namely, no, phase, lag, and
      complete synchronization, are identified. Furthermore, dynamics from the
      different transition intervals are also characterized.

PMID- 17500748
TI  - Subharmonic transitions in a bistable oscillator with bimodal periodic
      excitation.
AB  - We analyze the phenomenon of low-frequency signal enhancement in a bistable
      system excited by a sum of low-frequency and high-frequency harmonic signals. A
      mechanism alternate to chaotic resonance is discussed. It is shown that a high
      frequency signal may generate interwell transitions of subharmonic frequency. If
      the frequency of the slow signal is equal or close to a subharmonic frequency of
      the fast signal, then the improvement of the low-frequency constituent in the
      output spectrum is due to sustained subharmonic resonance.

PMID- 17500749
TI  - Spectral properties of Bunimovich mushroom billiards.
AB  - Properties of a quantum mushroom billiard in the form of a superconducting
      microwave resonator have been investigated. They reveal unexpected nonuniversal
      features such as, e.g., a supershell effect in the level density and a dip in the
      nearest-neighbor spacing distribution. Theoretical predictions for the quantum
      properties of mixed systems rely on the sharp separability of phase space--an
      unusual property met by mushroom billiards. We however find deviations which are
      ascribed to the presence of dynamic tunneling.

PMID- 17500750
TI  - Fractional behavior in nonergodic reaction processes of isomerization.
AB  - We present numerical evidence of fractional behavior in reactions for a prototype
      model of three-degree-of-freedom isomerization. The survival probability in the
      well exhibits two distinct ranges of time scales: one where it decreases with a
      power law, and the other where it decreases exponentially. Trajectories
      corresponding to power law decays exhibit 1/f spectra and subdiffusion in action
      space, and those with exponential decays exhibit Lorentzian spectra and normal
      diffusion. The existence of these two types of behavior is explained on the basis
      of nonergodicity in the network of nonlinear resonances (Arnold web) in the well,
      and connection between the saddle and the Arnold web. Implications of the
      fractional dynamics are discussed in terms of Maxwell's demon in molecules.

PMID- 17500751
TI  - Route to non-Gaussian statistics in convective turbulence.
AB  - Motivated by the work of Li and Meneveau [Phys. Rev. Lett. 95, 164502 (2005)], we
      propose and solve a model for the Lagrangian evolution of both longitudinal and
      transverse velocity and temperature increments for Boussinesq convection. From
      this model, the short-time evolution of an initially imposed Gaussian joint
      probability density function (PDF) of both velocity and temperature increments is
      computed analytically and the trend to non-Gaussian statistics shown in a
      quantitative way. Predictions for moments of the joint PDF are obtained and their
      behavior analyzed with respect to known experimental and numerical results. The
      obtained results do not depend on the model free parameters, a fact in favor of
      their robustness.

PMID- 17500752
TI  - Improved Monte Carlo estimators for the one-body density.
AB  - An alternative Monte Carlo estimator for the one-body density rho(r) is
      presented. This estimator has a simple form and can be readily used in any type
      of Monte Carlo simulation. Comparisons with the usual regularization of the delta
      function on a grid show that the statistical errors are greatly reduced.
      Furthermore, our expression allows accurate calculations of the density at any
      point in space, even in the regions never visited during the Monte Carlo
      simulation. The method is illustrated with the computation of accurate
      variational Monte Carlo electronic densities for the Helium atom (one-dimensional
      curve) and for the water dimer (three-dimensional grid containing up to
      51x51x51=132,651 points).

PMID- 17500753
TI  - Enhancing robustness and immunization in geographical networks.
AB  - We find that different geographical structures of networks lead to varied
      percolation thresholds, although these networks may have similar abstract
      topological structures. Thus, strategies for enhancing robustness and
      immunization of a geographical network are proposed. Using the generating
      function formalism, we obtain an explicit form of the percolation threshold qc
      for networks containing arbitrary order cycles. For three-cycles, the dependence
      of qc on the clustering coefficients is ascertained. The analysis substantiates
      the validity of the strategies with analytical evidence.

PMID- 17500754
TI  - Phase transition and hysteresis in scale-free network traffic.
AB  - We model information traffic on scale-free networks by introducing the node queue
      length L proportional to the node degree and its delivering ability C
      proportional to L . The simulation gives the overall capacity of the traffic
      system, which is quantified by a phase transition from free flow to congestion.
      It is found that the maximal capacity of the system results from the case of the
      local routing coefficient phi slightly larger than zero, and we provide an
      analysis for the optimal value of phi. In addition, we report for the first time
      the fundamental diagram of flow against density, in which hysteresis is found,
      and thus we can classify the traffic flow with four states: free flow, saturated
      flow, bistable, and jammed.

PMID- 17500755
TI  - Unified Green's function retrieval by cross-correlation; connection with energy
      principles.
AB  - It has been shown theoretically and observationally that the Green's function for
      acoustic and elastic waves can be retrieved by cross-correlating fluctuations
      recorded at two locations. We extend the concept of the extraction of the Green's
      function to a wide class of scalar linear systems. For systems that are not
      invariant under time reversal, the fluctuations must be excited by volume sources
      in order to satisfy the energy balance (equipartitioning) that is needed to
      extract the Green's function. The general theory for retrieving the Green's
      function is illustrated with examples that include the diffusion equation,
      Schrodinger's equation, a vibrating string, the acoustic wave equation, a
      vibrating beam, and the advection equation. Examples are also shown of situations
      where the Green's function cannot be extracted from ambient fluctuations. The
      general theory opens up new applications for the extraction of the Green's
      function from field correlations that include flow in porous media, quantum
      mechanics, and the extraction of the response of mechanical structures such as
      bridges.

PMID- 17500756
TI  - Low-cost search in scale-free networks.
AB  - We study local search algorithms for networks with heterogeneous edge weights,
      testing them on scale-free and Erdos-Renyi networks. We assume that the location
      of the destination node is discovered when it is two edges away, and that the
      search cost is additive. It was previously shown that a search strategy
      preferring high-degree nodes reduces the average search cost over a simple random
      walk. In the prior work, for the case when the edge costs are randomly
      distributed, a different preference was investigated [high local betweenness
      centrality (LBC)], and was found to be superior to high-degree preference in
      scale-free networks, with the exception for the most sparse ones. We have found
      several preference criteria that are simpler and which, in all networks we
      tested, yield a lower cost than other criteria including high-degree, high-LBC,
      and low-edge cost.

PMID- 17500757
TI  - Structural bottlenecks for communication in networks.
AB  - We consider the effect of network topology on the optimality of packet routing
      which is quantified by gammac, the rate of packet insertion beyond which
      congestion and queue growth occurs. We show that for any network, there exists an
      absolute upper bound, expressed in terms of vertex separators, for the scaling of
      gammac with network size N, irrespective of the static routing protocol used. We
      then derive an estimate to this upper bound for scale-free networks and introduce
      a static routing protocol, the "hub avoidance protocol," which, for large packet
      insertion rates, is superior to the shortest path routing protocol.

PMID- 17500758
TI  - Geographical networks evolving with an optimal policy.
AB  - In this article we propose a growing network model based on an optimal policy
      involving both topological and geographical measures. In this model, at each time
      step, a node, having randomly assigned coordinates in a 1x1 square, is added and
      connected to a previously existing node i, which minimizes the quantity
      ri2/kialpha, where ri is the geographical distance, ki the degree, and alpha a
      free parameter. The degree distribution obeys a power-law form when alpha=1, and
      an exponential form when alpha=0. When alpha is in the interval (0, 1), the
      network exhibits a stretched exponential distribution. We prove that the average
      topological distance increases in a logarithmic scale of the network size,
      indicating the existence of the small-world property. Furthermore, we obtain the
      geographical edge length distribution, the total geographical length of all
      edges, and the average geographical distance of the whole network. Interestingly,
      we found that the total edge length will sharply increase when alpha exceeds the
      critical value alphac=1, and the average geographical distance has an upper bound
      independent of the network size. All the results are obtained analytically with
      some reasonable approximations, which are well verified by simulations.

PMID- 17500759
TI  - Athermal shear-transformation-zone theory of amorphous plastic deformation. I.
      Basic principles.
AB  - We develop an athermal version of the shear-transformation-zone (STZ) theory of
      amorphous plasticity in materials where thermal activation of irreversible
      molecular rearrangements is negligible or nonexistent. In many respects, this
      theory has broader applicability and yet is simpler than its thermal
      predecessors. For example, it needs no special effort to assure consistency with
      the laws of thermodynamics, and the interpretation of yielding as an exchange of
      dynamic stability between jammed and flowing states is clearer than before. The
      athermal theory presented here incorporates an explicit distribution of STZ
      transition thresholds. Although this theory contains no conventional thermal
      fluctuations, the concept of an effective temperature is essential for
      understanding how the STZ density is related to the state of disorder of the
      system.

PMID- 17500760
TI  - Athermal shear-transformation-zone theory of amorphous plastic deformation. II.
      Analysis of simulated amorphous silicon.
AB  - In the preceding paper, we developed an athermal shear-transformation-zone (STZ)
      theory of amorphous plasticity. Here we use this theory in an analysis of
      numerical simulations of plasticity in amorphous silicon by Demkowicz and Argon
      (DA). In addition to bulk mechanical properties, those authors observed internal
      features of their deforming system that challenge our theory in important ways.
      We propose a quasithermodynamic interpretation of their observations in which the
      effective disorder temperature, generated by mechanical deformation well below
      the glass temperature, governs the behavior of other state variables that fall in
      and out of equilibrium with it. Our analysis points to a limitation of either the
      step-strain procedure used by DA in their simulations, or the STZ theory in its
      ability to describe rapid transients in stress-strain curves, or perhaps to both.
      Once we allow for this limitation, we are able to bring our theoretical
      predictions into accurate agreement with the simulations.

PMID- 17500761
TI  - Cascading dynamics in modular networks.
AB  - In this paper we study a simple cascading process in a structured heterogeneous
      population, namely, a network composed of two loosely coupled communities. We
      demonstrate that under certain conditions the cascading dynamics in such a
      network has a two-tiered structure that characterizes activity spreading at
      different rates in the communities. We study the dynamics of the model using both
      simulations and an analytical approach based on annealed approximation and obtain
      good agreement between the two. Our results suggest that network modularity might
      have implications in various applications, such as epidemiology and viral
      marketing.

PMID- 17500762
TI  - Weighted network analysis of high-frequency cross-correlation measures.
AB  - In this paper we implement a Fourier method to estimate high-frequency
      correlation matrices from small data sets. The Fourier estimates are shown to be
      considerably less noisy than the standard Pearson correlation measures and thus
      capable of detecting subtle changes in correlation matrices with just a month of
      data. The evolution of correlation at different time scales is analyzed from the
      full correlation matrix and its minimum spanning tree representation. The
      analysis is performed by implementing measures from the theory of random weighted
      networks.

PMID- 17500763
TI  - Role of unstable periodic orbits in phase transitions of coupled map lattices.
AB  - The thermodynamic formalism for dynamical systems with many degrees of freedom is
      extended to deal with time averages and fluctuations of some macroscopic quantity
      along typical orbits, and applied to coupled map lattices exhibiting phase
      transitions. Thereby, it turns out that a seed of phase transition is embedded as
      an anomalous distribution of unstable periodic orbits, which appears as a so
      called q-phase transition in the spatiotemporal configuration space. This
      intimate relation between phase transitions and q-phase transitions leads to one
      natural way of defining transitions and their order in extended chaotic systems.
      Furthermore, a basis is obtained on which we can treat locally introduced control
      parameters as macroscopic "temperature" in some cases involved with phase
      transitions.

PMID- 17500764
TI  - Wave trains in an excitable FitzHugh-Nagumo model: bistable dispersion relation
      and formation of isolas.
AB  - We investigate the dispersion relations of nonlinear periodic wave trains in
      excitable systems which describe the dependence of the propagation velocity on
      the wavelength. Pulse interaction by oscillating pulse tails within a wave train
      leads to bistable wavelength bands, in which two stable and one unstable wave
      train coexist for the same wavelength. The essential spectra of the unstable wave
      trains exhibit a circle of eigenvalues with positive real parts which is detached
      from the imaginary axis. We describe the destruction of the bistable dispersion
      curve and the formation of isolas of wave trains in a sequence of transcritical
      bifurcations unfolding into pairs of saddle-node bifurcations. It turns out that
      additional dispersion curves of unstable wave trains play an important role in
      the destruction of the bistable dispersion curve.

PMID- 17500765
TI  - Convection patterns in colloidal solutions.
AB  - We investigate the bifurcation properties and pattern selection in Rayleigh
      Benard convecting binary mixtures for parameter combinations that are typical for
      colloidal fluids using the Galerkin method. In such fluids the typical Lewis
      numbers and separation ratios differ by orders of magnitude from the values found
      in molecular mixtures like alcohol/water. We study stationary rolls, square and
      crossroll patterns for positive separation ratios, and traveling waves for
      negative separation ratios. Results are compared to those for molecular mixtures.

PMID- 17500766
TI  - Nodal domains in open microwave systems.
AB  - Nodal domains are studied both for real psiR and imaginary part psiI of the wave
      functions of an open microwave cavity and found to show the same behavior as wave
      functions in closed billiards. In addition we investigate the variation of the
      number of nodal domains and the signed area correlation by changing the global
      phase phig according to psiR+ipsiI=eiphig(psiR'+ipsiI'). This variation can be
      qualitatively, and the correlation quantitatively explained in terms of the phase
      rigidity characterizing the openness of the billiard.

PMID- 17500767
TI  - Two types of phase synchronization destruction.
AB  - In this paper we report that there are two different types of destruction of the
      phase synchronization (PS) regime of chaotic oscillators depending on the
      parameter mismatch as well as in the case of the classical synchronization of
      periodic oscillators. When the parameter mismatch of the interacting chaotic
      oscillators is small enough, the PS breaking takes place without the destruction
      of the phase coherence of chaotic attractors of oscillators. Alternatively, due
      to the large frequency detuning, the PS breaking is accomplished by loss of the
      phase coherence of the chaotic attractors.

PMID- 17500768
TI  - Triggering and enhancing chaos with a prescribed target Lyapunov exponent using
      optimized perturbations of minimum power.
AB  - The objective of the present work is to propose a method for nonfeedback
      anticontrol of chaos with perturbations of minimum power for a preset control
      goal. The noted Lorenz system is employed as the test model for chaotification
      with the target state specified by a prescribed positive value of the largest
      Lyapunov exponent (LLE), lambda[over ]>0 . Periodic and quasiperiodic
      perturbations are used as control signals, and the signals parameters are
      optimized using a genetic algorithm under restriction of minimum power.
      Performance of the optimized signals in triggering chaos at an ordered state,
      fixed point or periodic, as well as further enhancing chaoticity at a chaotic
      state is explored. The present numerical experiments reveal the following
      interesting physics about chaotification. In general, the power for
      chaotification increases with the preset value of lambda and quasiperiodic
      signals can achieve the control goal with a lower power than periodic ones. Given
      the same increment of LLE from that of the uncontrolled state (lambda1,0) , i.e.,
      Deltalambda=lambda-lambda1,0, the further enhancement of chaoticity in a chaotic
      state needs a higher control power than the triggering of chaos from an ordered
      state. The minimum power required for chaotification of an ordered state
      increases relatively slowly for lower lambda[over ] but increases drastically as
      the preset target LLE reaches a certain critical value. Most strikingly, the
      numerical experiments demonstrate that this critical value of lambda corresponds
      to LLE of the nearest chaotic state in the neighborhood of the uncontrolled
      state. Robustness of applying the present method in the presence of external
      noise is also demonstrated.

PMID- 17500769
TI  - Multipeaked probability distributions of recurrence times.
AB  - We determine probabilities of recurrence time into finite-sized, physically
      meaningful subsets of phase space. We consider three different autonomous chaotic
      systems: (i) scattering in a three-peaked potential, (ii) connected billiards,
      and (iii) Lorenz equations. We find multipeaked probability distributions,
      similar to the distributions found in (driven) stochastically resonant systems.
      In nondriven systems, such as ours, only monotonic decaying distributions
      (exponentials, stretched exponentials, power laws, and slight variations or
      combinations of these) have hitherto been reported. Discrete peaks in autonomous
      systems have as yet escaped attention in autonomous systems and correspond to
      specific trajectory subsets involving an integer number of loops.

PMID- 17500770
TI  - Mode locking of a driven Bose-Einstein condensate.
AB  - We consider the dynamics of a driven Bose-Einstein condensate with positive
      scattering length. Employing an accustomed variational treatment we show that
      when the scattering length is time modulated as a{1+epsilonsin[omega(t)t]}, where
      omega(t) increases linearly in time, i.e., omega(t)=gammat, the response
      frequency of the condensate locks to the eigenfrequency for small values of
      epsilon and gamma. A simple analytical model is presented which explains this
      phenomenon by mapping it to an auto-resonance, i.e., close to resonance the
      reduced equations describing the collective behavior of the condensate are
      equivalent to those of a virtual particle trapped in a finite-depth energy
      minimum of an effective potential.

PMID- 17500771
TI  - Noise-induced turbulence in nonlocally coupled oscillators.
AB  - We demonstrate that nonlocally coupled limit-cycle oscillators subject to
      spatiotemporally white Gaussian noise can exhibit a noise-induced transition to
      turbulent states. After illustrating noise-induced turbulent states with
      numerical simulations using two representative models of limit-cycle oscillators,
      we develop a theory that clarifies the effective dynamical instabilities leading
      to the turbulent behavior using a hierarchy of dynamical reduction methods. We
      determine the parameter region where the system can exhibit noise-induced
      turbulent states, which is successfully confirmed by extensive numerical
      simulations at each level of the reduction.

PMID- 17500772
TI  - Failure of maximum likelihood methods for chaotic dynamical systems.
AB  - The maximum likelihood method is a basic statistical technique for estimating
      parameters and variables, and is the starting point for many more sophisticated
      methods, like Bayesian methods. This paper shows that maximum likelihood fails to
      identify the true trajectory of a chaotic dynamical system, because there are
      trajectories that appear to be far more (infinitely more) likely than truth. This
      failure occurs for unbounded noise and for bounded noise when it is sufficiently
      large and will almost certainly have consequences for parameter estimation in
      such systems. The reason for the failure is rather simple; in chaotic dynamical
      systems there can be trajectories that are consistently closer to the
      observations than the true trajectory being observed, and hence their likelihood
      dominates truth. The residuals of these truth-dominating trajectories are not
      consistent with the noise distribution; they would typically have too small
      standard deviation and many outliers, and hence the situation may be remedied by
      using methods that examine the distribution of residuals and are not entirely
      maximum likelihood based.

PMID- 17500773
TI  - Noise effects on gap wave propagation in a nonlinear discrete LC transmission
      line.
AB  - We report here the results of numerical investigation of noise effects on the
      propagation in a nonlinear waveguide modeled by a discrete electrical line.
      Considering a periodic signal of frequency exceeding the natural cutoff frequency
      of this system, we show that noise can be used to trigger soliton generation in
      the medium. Besides the classical stochastic resonance signature exhibited by
      each oscillator of the network, our simulation results reveal in particular that
      the signal-to-noise ratio remains almost constant in the whole network for an
      appropriate amount of noise. This interesting feature insures for the generated
      solitons a quality preserved propagation along the network.

PMID- 17500774
TI  - Resonant forcing of multidimensional chaotic map dynamics.
AB  - We study resonances of chaotic map dynamics. We use the calculus of variations to
      determine the additive forcing function that induces the largest response. We
      find that resonant forcing functions complement the separation of nearby
      trajectories, in that the product of the displacement of nearby trajectories and
      the resonant forcing is a conserved quantity. As a consequence, the resonant
      function will have the same periodicity as the displacement dynamics, and if the
      displacement dynamics is irregular, then the resonant forcing function will be
      irregular as well. Furthermore, we show that resonant forcing functions of
      chaotic systems decrease exponentially, where the rate equals the negative of the
      largest Lyapunov exponent of the unperturbed system. We compare the response to
      optimal forcing with random forcing and find that the optimal forcing is
      particularly effective if the largest Lyapunov exponent is significantly larger
      than the other Lyapunov exponents. However, if the largest Lyapunov exponent is
      much larger than unity, then the optimal forcing decreases rapidly and is only as
      effective as a single-push forcing.

PMID- 17500775
TI  - Fractal properties of anomalous diffusion in intermittent maps.
AB  - An intermittent nonlinear map generating subdiffusion is investigated. Computer
      simulations show that the generalized diffusion coefficient of this map has a
      fractal, discontinuous dependence on control parameters. An amended continuous
      time random-walk theory well approximates the coarse behavior of this quantity in
      terms of a continuous function. This theory also reproduces a full suppression of
      the strength of diffusion, which occurs at the dynamical transition from normal
      to anomalous diffusion. Similarly, the probability density function of this map
      exhibits a nontrivial fine structure while its coarse functional form is governed
      by a time fractional diffusion equation. A more detailed understanding of the
      irregular structure of the generalized diffusion coefficient is provided by an
      anomalous Taylor-Green-Kubo formula establishing a relation to de Rham-type
      fractal functions.

PMID- 17500776
TI  - Dynamics of Bose-Einstein condensates under the influence of periodic and
      harmonic potentials.
AB  - A variational method is developed to describe the dynamics of a Bose-Einstein
      condensate (BEC) trapped in an applied external potential consisting of both a
      harmonic and periodic component. Using this variational method, the BEC dynamics
      is shown to be well approximated by four coupled nonlinear differential
      equations, which describe the fundamental interactions in the system arising from
      the interplay of amplitude (width), chirp, center position, and center frequency.
      The simplified analytic theory allows for an efficient and convenient method for
      characterizing the experimental BEC behavior when localized condensates are
      generated. It further gives the critical strength ratio of harmonic to periodic
      potential necessary to support multiple stable lattice sites for the condensate
      and demonstrates that there can be an underlying chaotic behavior in the
      condensate system.

PMID- 17500777
TI  - Curved structures in recurrence plots: the role of the sampling time.
AB  - We give a theoretical explanation of the formation of the curved macropatterns in
      the recurrence plots of sinusoidal signals, with nonstationarity in the phase or
      in the frequency. We show that the large time scales observed and the curved
      structures are the artificial product of the discretization of the signal.
      Recurrence plots are highly sensitive to the phase error introduced by the
      sampling, and we show that this characteristic can be used to detect very small
      (approximately 0.5%) phase or frequency shifts of the carrier frequency.

PMID- 17500778
TI  - Signature of ray chaos in quasibound wave functions for a stadium-shaped
      dielectric cavity.
AB  - Light emission from a dielectric cavity with a stadium shape is studied in both
      ray and wave models. For a passive cavity mode with low loss, a remarkable
      correspondence is found between the phase space representation of a quasibound
      wave function and its counterpart distribution in the ray model. This result
      provides additional and more direct evidence for good ray-wave correspondence in
      low-loss modes previously observed at the level of far-field emission pattern
      comparisons.

PMID- 17500779
TI  - Recovery of classical chaoticlike behavior in a conservative quantum three-body
      problem.
AB  - Recovering trajectories of quantum systems whose classical counterparts display
      chaotic behavior has been a subject that has received a lot of interest over the
      last decade. However, most of these studies have focused on driven and
      dissipative systems. The relevance and impact of chaotic-like phenomena to
      quantum systems has been highlighted in recent studies which have shown that
      quantum chaos is significant in some aspects of quantum computation and
      information processing. In this paper we study a three-body system comprising of
      identical particles arranged so that the system's classical trajectories exhibit
      Hamiltonian chaos. Here we show that it is possible to recover very nearly
      classical-like, conservative, chaotic trajectories from such a system through an
      unravelling of the master equation. First, this is done through continuous
      measurement of the position of each system. Second, and perhaps somewhat
      surprisingly, we demonstrate that we still obtain a very good match between the
      classical and quantum dynamics by weakly measuring the position of only one of
      the oscillators.

PMID- 17500780
TI  - Singular unlocking transition in the Winfree model of coupled oscillators.
AB  - The Winfree model consists of a population of globally coupled phase oscillators
      with randomly distributed natural frequencies. As the coupling strength and the
      spread of natural frequencies are varied, the various stable states of the model
      can undergo bifurcations, nearly all of which have been characterized previously.
      The one exception is the unlocking transition, in which the frequency-locked
      state disappears abruptly as the spread of natural frequencies exceeds a critical
      width. Viewed as a function of the coupling strength, this critical width defines
      a bifurcation curve in parameter space. For the special case where the frequency
      distribution is uniform, earlier work had uncovered a puzzling singularity in
      this bifurcation curve. Here we seek to understand what causes the singularity.
      Using the Poincare-Lindstedt method of perturbation theory, we analyze the locked
      state and its associated unlocking transition, first for an arbitrary
      distribution of natural frequencies, and then for discrete systems of N
      oscillators. We confirm that the bifurcation curve becomes singular for a
      continuum uniform distribution, yet find that it remains well behaved for any
      finite N , suggesting that the continuum limit is responsible for the
      singularity.

PMID- 17500781
TI  - Analytic approach for controlling quantum states in complex systems.
AB  - We examine random matrix systems driven by an external field in view of optimal
      control theory (OCT). By numerically solving OCT equations, we can show that
      there exists a smooth transition between two states called "moving bases" which
      are dynamically related to initial and final states. In our previous work [J.
      Phys. Soc. Jpn. 73, 3215 (2004); Adv. Chem. Phys. 130A, 435 (2005)], they were
      assumed to be orthogonal, but in this paper, we introduce orthogonal moving
      bases. We can construct a Rabi-oscillation-like representation of a wave packet
      using such moving bases, and derive an analytic optimal field as a solution of
      the OCT equations. We also numerically show that the newly obtained optimal field
      outperforms the previous one.

PMID- 17500782
TI  - Heterogeneity-induced defect bifurcation and pulse dynamics for a three-component
      reaction-diffusion system.
AB  - We consider the dynamics when traveling pulses encounter heterogeneities in a
      three-component reaction diffusion system of one-activator-two-inhibitor type,
      which typically arises as a qualitative model of a gas-discharge system. We
      focused on the case where one of the kinetic coefficients changes similar to a
      smoothed step function, which is basic for more general heterogeneity as in
      periodic or random media. Since the heterogeneity is introduced to the kinetic
      part in an additive way, it causes the system to produce various types of
      localized structures smoothing the jump heterogeneity called the defects at the
      jump point, which makes a sharp contrast with the multiplicative heterogeneous
      case for the Gray-Scott model. The main issue is to study the collision dynamics
      between traveling pulses and defects, and show that their global bifurcation
      structure plays a key role in clarifying the underlying mechanism. Five outputs
      are observed after collisions including annihilation, rebound, and pinning.
      Unstable steady states are identified as separators between two different dynamic
      regimes: penetration and rebound, the role of which is very close to that of
      scattors arising in collision process. An organizing center producing the
      traveling pulses, defects, and scattors via unfolding with respect to the
      parameters is also presented.

PMID- 17500783
TI  - Quantum entropy dynamics for chaotic systems beyond the classical limit.
AB  - The entropy production rate for an open quantum system with a classically chaotic
      limit has been previously argued to be independent of h and D, the parameter
      denoting coupling to the environment, and to be equal to the sum of generalized
      Lyapunov exponents, with these results applying in the near-classical regime. We
      present results for a specific system going well beyond earlier work, considering
      how these dynamics are altered for the Duffing problem by changing h,D and show
      that the entropy dynamics have a transition from classical to quantum behavior
      that scales, at least for a finite time, as a function of h2/D.

PMID- 17500784
TI  - Recurrence analysis of strange nonchaotic dynamics.
AB  - We present methods to detect the transitions from quasiperiodic to chaotic motion
      via strange nonchaotic attractors (SNAs). These procedures are based on the time
      needed by the system to recur to a previously visited state and a quantification
      of the synchronization of trajectories on SNAs. The applicability of these
      techniques is demonstrated by detecting the transition to SNAs or the transition
      from SNAs to chaos in representative quasiperiodically forced discrete maps. The
      fractalization transition to SNAs--for which most existing diagnostics are
      inadequate--is clearly detected by recurrence analysis. These methods are robust
      to additive noise, and thus can be used in analyzing experimental time series.

PMID- 17500785
TI  - Intrusion of nonwetting liquid in paper.
AB  - The saturation curve of a sample of paper board was measured with mercury
      intrusion porosimetry, and the three-dimensional structure of its pore space was
      determined by x-ray tomographic imaging. Ab initio numerical simulation of
      intrusion on the tomographic reconstruction, based on the lattice-Boltzmann
      method, was in excellent agreement with the measured saturation curve. A
      numerical invasion-percolation simulation in the same tomographic reconstruction
      showed good agreement with the lattice-Boltzmann simulation. The access function
      of the sample, determined from the saturation curve and the pore-throat
      distribution determined from the tomographic reconstruction, indicated that the
      ink-bottle effect is significant in paperlike materials.

PMID- 17500786
TI  - Eigenfrequencies of vortex-pair equilibria near an elliptic cylinder or a flat
      plate in uniform flow.
AB  - The eigenfrequencies of the potential-flow equilibria of a symmetric vortex pair
      behind an elliptic cylinder in uniform flow are calculated through the use of
      conformal mapping. These frequencies are shown to have values in agreement with
      measured Strouhal numbers reported in various papers. The special cases of the
      potential-flow equilibrium of a symmetric vortex pair behind a circular cylinder
      and the equilibrium behind a flat plate perpendicular to the uniform flow, are
      related to the measured Strouhal numbers of about 0.21 and 0.15, respectively. It
      is suggested that in the range of subcritical Reynolds numbers, 3x10(2) to
      5x10(5) for the circular cylinder, a part of the drag is the result of the
      presence of a mean recirculation region in the near wake, which sheds vortices in
      the far wake and which is fed by vorticity from the cylinder wall.

PMID- 17500787
TI  - Critical parameters for the partial coalescence of a droplet.
AB  - The partial coalescence of a droplet onto a planar liquid-liquid interface is
      investigated experimentally by tuning the viscosities of both liquids. The
      problem mainly depends on four dimensionless parameters: The Bond number (gravity
      vs surface tension), the Ohnesorge numbers (viscosity in both fluids vs surface
      tension), and the density relative difference. The ratio between the daughter
      droplet size and the mother droplet size is investigated as a function of these
      dimensionless numbers. Global quantities such as the available surface energy of
      the droplet have been measured during the coalescence. The capillary waves
      propagation and damping are studied in detail. The relation between these waves
      and the partial coalescence is discussed. Additional viscous mechanisms are
      proposed in order to explain the asymmetric role played by both viscosities.

PMID- 17500788
TI  - Dynamic van der Waals theory.
AB  - We present a dynamic van der Waals theory starting with entropy and energy
      functional with gradient contributions. The resultant hydrodynamic equations
      contain the stress arising from the density gradient. It provides a general
      scheme of two-phase hydrodynamics involving the gas-liquid transition in
      nonuniform temperature. Some complex hydrodynamic processes with evaporation and
      condensation are examined numerically. They are (i) adiabatically induced
      spinodal decomposition, (ii) piston effect with a bubble in liquid, (iii)
      temperature and velocity profiles around a droplet in heat flow, (iv) efficient
      latent heat transport at small liquid densities (the mechanism of heat pipes),
      (v) boiling in gravity with continuous bubble formation and rising, and (vi)
      spreading and evaporation of liquid on a heated boundary wall.

PMID- 17500789
TI  - Forced imbibition in natural porous media: comparison between experiments and
      continuum models.
AB  - A well-characterized set of large-scale laboratory experiments is presented,
      illustrating forced imbibition displacements in the presence of irreducible
      wetting phase saturation in a cylindrical, homogeneous Berea sandstone rock.
      Experiments are designed to operate in the regime of compact microscopic flows
      and large-scale viscous instability. The distribution of fluid phases during the
      flow process is visualized by high-resolution computed tomography imaging. Linear
      stability analysis and high-accuracy numerical simulations are employed to
      analyze the ability of macroscopic continuum equations to provide a consistent
      approximation of the displacement process. The validity of the equilibrium
      relative permeability functions, which form the basis for the continuum model, is
      fundamentally related to the stability of the displacement process. It is shown
      that not only is the stable flow regime modeled accurately by existing continuum
      models, but the onset of instability as well as the initial unstable modes are
      also determined with reasonable accuracy for unstable flows. However, the
      continuum model is found to be deficient in the case of fully developed unstable
      flows.

PMID- 17500790
TI  - Role of base flows on surfactant-driven interfacial instabilities.
AB  - In this paper, we examine how base flows affect interfacial stabilities in the
      presence of surfactants. A thin-film flow model, subjected to various base-flow
      conditions, is employed to mimic a wide class of practical interfacial flows. The
      base flow can be driven by an external force (e.g., pressure forcing or gravity),
      an interfacial stress, or their combination. For long-wave perturbations, we show
      that the stability is governed by a coupled set of evolution equations for the
      interface and surfactant concentration, so the origin of the stability can be
      unraveled analytically in line with simpler physical arguments. We also
      demonstrate that the system can exhibit a variety of stability states; it can be
      neutral, conditionally stable or unstable, or definitely stable or unstable,
      determined solely by the nature of the base flow and how it regulates surfactant
      transport. Two modes are found to determine the stability, the interface and
      surfactant modes, and characterized by the ratio of the basic interfacial shear
      force to the external force. The routes to the instability are also identified
      through the action of the base flow. The base flow plays a dual role in affecting
      the stability: although the imposition of an interfacial shear destabilizes the
      interface, an external force can cause stabilization. The competition between
      these two effects gives rise to stability or instability in a range of the force
      ratio. The underlying mechanisms are elucidated in detail. A generalized
      criterion for the onset of instability is also established for one- or two-fluid
      interfacial flows.

PMID- 17500791
TI  - Role of pressure in nonlinear velocity gradient dynamics in turbulence.
AB  - To identify and understand the effect of pressure on turbulence velocity gradient
      dynamics, we study the velocity gradient evolution with the inviscid three
      dimensional Burgers equation and the restricted Euler equation (REE). While the
      REE represents the incompressible limit of turbulence, the Burgers equation is
      taken to be the infinite Mach number model for the Navier-Stokes equation wherein
      the time scale of flow inertia is very small compared to that of pressure.
      Analytical fixed-point solutions for the velocity gradient tensor are obtained in
      the two cases. The results are compared and contrasted to isolate the role of
      pressure in shaping velocity gradient behavior. Of particular interest is the
      influence of pressure on (i) the strain rate eigenvalues; (ii) the sign of the
      intermediate principal strain rate; (iii) the tendency of vorticity to align with
      the intermediate principal strain rate; and (iv) the energy cascade direction.
      Importantly, the study provides valuable insight into the velocity gradient
      dynamics in highly compressible turbulence.

PMID- 17500792
TI  - Abnormal mixing of passive scalars in chaotic flows.
AB  - We study the relaxation of a passive scalar towards the uniform equilibrium
      distribution in an advection-diffusion problem where the phase space for the pure
      advection problem is a mixture of chaotic domains and elliptic islands. Since the
      advection-diffusion problem is linear, the relaxation can be characterized by the
      eigenvalues and eigenmodes of the evolution operator. Almost degenerate
      eigenvalues then give rise to deviations from simple exponential decay behavior.
      We show by example that the corresponding eigenmodes can be supported by islands
      or weakly connected chaotic domains. These theoretical considerations are related
      to some experimental observations in two-dimensional flows.

PMID- 17500793
TI  - Attractor crisis and bursting in a fluid flow with two no-slip directions.
AB  - Characteristic bursting behavior is observed in a driven, two-dimensional viscous
      flow, confined to a square domain and subject to no-slip boundaries. Passing a
      critical parameter value, an existing chaotic attractor undergoes a crisis, after
      which the flow initially enters a transient bursting regime. Bursting is caused
      by ejections from and return to a limited subdomain of the phase space, whereas
      the precrisis chaotic set forms the asymptotic attractor of the flow. For
      increasing values of the control parameter the length of the bursting regime
      increases progressively. Passing another critical parameter value, a second
      crisis leads to the appearance of a secondary type of bursting, of very large
      dynamical range. Within the bursting regime the flow then switches in irregular
      intervals from the primary to the secondary type of bursting. Peak enstrophy
      levels for both types of bursting are associated to the collapse of a primary
      vortex into a quadrupolar state.

PMID- 17500794
TI  - Fingering patterns in the lifting flow of a confined miscible ferrofluid.
AB  - Miscible flow displacements of a ferrofluid droplet subjected to various magnetic
      field configurations and confined in a time-dependent gap Hele-Shaw cell are
      examined through highly accurate numerical simulations. The interplay between
      lifting, miscibility, and applied magnetic fields resulted in complex interfacial
      pattern formation. By varying the symmetry properties of the applied magnetic
      fields and by considering the action of Korteweg stresses, a number of
      interesting droplet morphologies are identified and characterized. The
      possibility of controlling the degree of fluid mixing and the ultimate shape of
      the emerging patterns by appropriately adjusting the strength of the applied
      magnetic fields is also discussed.

PMID- 17500795
TI  - Fluid pinch-off in superfluid and normal 4He.
AB  - We present frames from high-speed videos of the pinch-off of liquid 4He droplets.
      The temperature of the fluid droplets ranged from 1.33 K to 4.8 K, and the size
      of the drops was proportional to the temperature-dependent capillary length. We
      observed no qualitative difference between pinch-off in the normal and superfluid
      states. In both cases, the shape of the fluid in the final stages of pinch-off
      resembles a cone piercing a sphere, which is typical of other low-viscosity
      fluids. The evolution of the minimum neck radius rmin can be characterized by
      power laws rmin proportional, taun, where tau is the time remaining until pinch
      off occurs. In the regime near pinch-off, the data from image analysis are
      consistent with n=2/3. The data at the beginning of the pinch process when the
      neck is of the order of the capillary length are also described by n=2/3, but
      with a different proportionality factor. There is an intermediate crossover
      regime characterized by n=2/5.

PMID- 17500796
TI  - Maximal oil recovery by simultaneous condensation of alkane and steam.
AB  - This paper deals with the application of steam to enhance the recovery from
      petroleum reservoirs. We formulate a mathematical and numerical model that
      simulates coinjection of volatile oil with steam into a porous rock in a one
      dimensional setting. We utilize the mathematical theory of conservation laws to
      validate the numerical simulations. This combined numerical and analytical
      approach reveals the detailed mechanism for thermal displacement of oil mixtures
      discovered in laboratory experiments. We study the structure of the solution,
      determined by the speeds and amplitudes of the several nonlinear waves involved.
      Thus we show that the oil recovery depends critically on whether the boiling
      point of the volatile oil is around the water boiling temperature, or much below
      or above it. These boiling-point ranges correspond to three types of wave
      structures. When the boiling point of the volatile oil is near the boiling point
      of water, the striking result is that the speed of the evaporation front is equal
      or somewhat larger than the speed of the steam condensation front. Thus the
      volatile oil condenses at the location where the steam condenses too, yielding
      virtually complete oil recovery. Conversely, if the boiling point is too high or
      too low, there is incomplete recovery. The condensed volatile oil stays at the
      steam condensation location because the steam condensation front is a physical
      shock.

PMID- 17500797
TI  - Nanosecond near-spinodal homogeneous boiling of water superheated by a pulsed CO2
      laser.
AB  - The fast boiling dynamics of superheated surface layers of bulk water cavitating
      under near-spinodal conditions during nanosecond CO2 laser heating pulses was
      studied using contact broad-band photoacoustic spectroscopy. Characteristic
      pressure-tension cycles recorded by an acoustic transducer at different incident
      laser fluences represent (a) weak random oscillations of transient nanometer
      sized near-critical bubbles-precursors and (b) well-defined stimulated
      oscillations of micron-sized supercritical bubbles and their submicrosecond
      coalescence products. These findings provide an important insight into basic
      thermodynamic parameters, spatial and temporal scales of bubble nucleation during
      explosive liquid/vapor transformations in absorbing liquids ablated by short
      laser pulses in the thermal confinement regime.

PMID- 17500798
TI  - Width of a ferrofluid finger: hysteresis and a double energy minimum.
AB  - We study a ferrofluid in a horizontal Hele-Shaw geometry subjected to a vertical
      magnetic field. Specifically, we calculate the energy of a single ferrofluid
      finger using an idealized model for the finger. By minimizing this energy, we
      find the preferred finger width as a function of the applied field. Our model
      predicts a first order transition as the fluid abruptly transforms from a
      circular drop to a finite finger. This behavior arises because of a double energy
      minimum that yields two different stable configurations for the system.
      Interestingly, this system exhibits hysteresis as the circle-to-finger
      (increasing field) transition occurs at a different applied field than the finger
      to-circle (decreasing field) transition. We carry out a simple experiment and
      observe good overall agreement with the theoretical predictions.

PMID- 17500799
TI  - Fast chemical reaction and multiple-scale concentration fields in singular
      vortices.
AB  - Two species involved in a simple, fast reaction tend to become segregated in
      patches composed of a single of these reactants. These patches are separated by a
      boundary where the stoichiometric condition is satisfied and the reaction occurs,
      fed by diffusion. Stirred by advection, this boundary and the concentration
      fields within the patches may tend to present multiple-scale characteristics.
      Based on this segregated state, this paper aims at evaluating the temporal
      evolutions of the length of the boundary and diffusive flux of reactants across
      it, when concentrations presenting initial self-similar fluctuations are advected
      by a singular vortex. First the two sources of singularity, i.e., the self
      similar initial conditions and the singular vortex, are considered separately. On
      the one hand, self-similar initial conditions are imposed to a diffusion-reaction
      system, for one- and two-dimensional cases. On the other hand, an imposed
      singular vortex advects initially on/off concentration fields, in combination
      with diffusion and reaction. This problem is addressed analytically, by
      characterizing the boundary by a box-counting dimension and the concentration
      fields by a Holder exponent, and numerically, by direct numerical simulations of
      the advection-diffusion-reaction equations. Second, the way the two sources hang
      together shows that, depending on the self-similar properties of the initial
      concentration fields, the vortex promotes the chemical activity close to its
      inner smoothed-out core or close to the outer region where the boundary starts to
      spiral. For all the considered situations, the length of the boundary and the
      global reaction speed are found to evolve algebraically with time after a short
      transient and a good agreement is found between the analytical and numerical
      scaling laws.

PMID- 17500800
TI  - Correlation effects in partially ionized mass asymmetric electron-hole plasmas.
AB  - The effects of strong Coulomb correlations in dense three-dimensional electron
      hole plasmas are studied by means of unbiased direct path integral Monte Carlo
      simulations. The formation and dissociation of bound states, such as excitons and
      biexcitons, is analyzed and the density-temperature region of their appearance is
      identified. At high density, the Mott transition to the fully ionized metallic
      state (electron-hole liquid) is detected. Particular attention is paid to the
      influence of the hole to electron mass ratio M on the properties of the plasma.
      Above a critical value of about M=80 formation of a hole Coulomb crystal was
      recently verified [Bonitz, Phys. Rev. Lett. 95, 235006 (2005)] which is supported
      by additional results. Results are related to the excitonic phase diagram of
      intermediate valent Tm[Se,Te], where large values of M have been observed
      experimentally.

PMID- 17500801
TI  - Production of a monoenergetic electron bunch in a self-injected laser-wakefield
      accelerator.
AB  - Production of a monoenergetic electron bunch in a self-injected laser-wakefield
      accelerator is investigated with a tomographic method which resolves the electron
      injection and acceleration processes. It is found that all the electrons in the
      monoenergetic electron bunch are injected at the same location in the plasma
      column and then accelerated with an acceleration gradient exceeding 2 GeV/cm. The
      injection position shifts with the position of pump-pulse focus, and no
      significant deceleration is observed for the monoenergetic electron bunch after
      it reaches the maximum energy. The results are consistent with the model of
      transverse wave breaking and beam loading for the injection of monoenergetic
      electrons. The tomographic method adds a crucial dimension to the whole array of
      existing diagnostics for laser beams, plasma waves, and electron beams. With this
      method the details of the underlying physical processes in laser-plasma
      interactions can be resolved and compared directly to particle-in-cell
      simulations.

PMID- 17500802
TI  - Degenerate four-wave mixing mediated by ponderomotive-force-driven plasma
      gratings.
AB  - Degenerate four-wave mixing mediated by ponderomotive-force-driven plasma
      gratings is demonstrated in the near-infrared regime. The quadratic dependence of
      the reflectivity of the probe pulse on plasma density indicates that the mixing
      is caused by the quasineutral plasma grating driven by the laser ponderomotive
      force. The experiment verifies that ponderomotive force is an effective means to
      produce a large-amplitude short-period plasma grating, which has many important
      applications in ultrahigh-intensity optics. In particular, such a grating is a
      crucial element for the development of plasma phase-conjugate mirrors that can be
      used to restore the wave-front distortion that is ubiquitous in nonlinear
      propagation.

PMID- 17500803
TI  - Modified Kubelka-Munk equations for localized waves inside a layered medium.
AB  - We present a pair of coupled partial differential equations to describe the
      evolution of the average total intensity and intensity flux of a wave field
      inside a randomly layered medium. These equations represent a modification of the
      Kubelka-Munk equations, or radiative transfer. Our modification accounts for wave
      interference (e.g., localization), which is neglected in radiative transfer. We
      numerically solve the modified Kubelka-Munk equations and compare the results to
      radiative transfer as well as to simulations of the wave equation with randomly
      located thin layers.

PMID- 17500804
TI  - Spatiotemporal bifurcations of a parametrically excited solitary wave.
AB  - The bifurcation behaviors of a parametrically excited solitary wave are
      investigated via Faraday's water tank experiment. It is observed that, as the
      driving frequency fd is decreased or/and the driving amplitude Ad is increased,
      the standing (but vertically oscillatory) solitary wave becomes modulationally
      unstable, leading to the temporal modulation of the vertical oscillation and the
      emergence of very low subharomic components on the frequency spectrum. Further
      lowering fd or/and increasing Ad will cause the modulational oscillation unstable
      and then, the peak of the solitary wave becomes rocking along the trough in the
      longitudinal direction. These bifurcations also give rise to the emission of
      continuous waves resulting in complex wave patterns and complicated fluctuations,
      especially for the quite low fd and large Ad. A possible route from solitary
      waves to chaos via bifurcations and mode competitions is therefore suggested on
      the basis of these observations.

PMID- 17500805
TI  - Parallel-plate metamaterials for cloaking structures.
AB  - In this work, we assess theoretically the physical response of metamaterial
      composite structures that emulate the behavior of negative-permittivity materials
      in certain relevant setups. The metamaterials under analysis consist of metallic
      parallel-plate implants embedded in a dielectric host in a two-dimensional
      geometry. Simple design rules and formulas are presented, fully considering the
      effect and consequences of excitation of higher-order diffraction modes at the
      metamaterial-dielectric interface. Following the ideas of transparency and
      cloaking developed by us [Alu and Engheta, Phys. Rev. E 72, 016623 (2005)], we
      demonstrate, analytically and numerically, that it is possible in this way to
      design metamaterial cloaks that significantly reduce the total scattering cross
      section of a given two-dimensional dielectric obstacle in some frequency band.
      This effect, which may be realized in a feasible way, may find interesting
      applications in electromagnetic cloaking, total scattering cross section
      reduction, and noninvasive probing.

PMID- 17500806
TI  - Moving and colliding pulses in the subcritical Ginzburg-Landau model with a
      standing-wave drive.
AB  - We show the existence of steadily moving solitary pulses (SPs) in the complex
      Ginzburg-Landau equation, which includes the cubic-quintic nonlinearity and a
      conservative linear driving term, whose amplitude is a standing wave with wave
      number k and frequency omega, the motion of the SPs being possible at resonant
      velocities +/-omega/k, which provide for locking to the drive. The model may be
      realized in terms of traveling-wave convection in a narrow channel with a
      standing wave excited in its bottom (or on the surface). An analytical
      approximation is developed, based on an effective equation of motion for the SP
      coordinate. Direct simulations demonstrate that the effective equation accurately
      predicts characteristics of the driven motion of pulses, such as a threshold
      value of the drive's amplitude. Collisions between two solitons traveling in
      opposite directions are studied by means of direct simulations, which reveal that
      they restore their original shapes and velocity after the collision.

PMID- 17500807
TI  - Universal fractal structures in the weak interaction of solitary waves in
      generalized nonlinear Schrodinger equations.
AB  - Weak interactions of solitary waves in the generalized nonlinear Schrodinger
      equations are studied. It is first shown that these interactions exhibit similar
      fractal dependence on initial conditions for different nonlinearities. Then by
      using the Karpman-Solov'ev method, a universal system of dynamical equations is
      derived for the velocities, amplitudes, positions, and phases of interacting
      solitary waves. These dynamical equations contain a single parameter, which
      accounts for the different forms of nonlinearity. When this parameter is zero,
      these dynamical equations are integrable, and the exact analytical solutions are
      derived. When this parameter is nonzero, the dynamical equations exhibit fractal
      structures which match those in the original wave equations both qualitatively
      and quantitatively. Thus the universal nature of fractal structures in the weak
      interaction of solitary waves is analytically established. The origin of these
      fractal structures is also explored. It is shown that these structures bifurcate
      from the initial conditions where the solutions of the integrable dynamical
      equations develop finite-time singularities. Based on this observation, an
      analytical criterion for the existence and locations of fractal structures is
      obtained. Lastly, these analytical results are applied to the generalized
      nonlinear Schrodinger equations with various nonlinearities such as the saturable
      nonlinearity, and predictions on their weak interactions of solitary waves are
      made.

PMID- 17500808
TI  - Dynamics of scattering on a classical two-dimensional artificial atom.
AB  - A classical two-dimensional (2D) model for an artificial atom is used to make a
      numerical "exact" study of elastic and nonelastic scattering. Interesting
      differences in the scattering angle distribution between this model and the well
      known Rutherford scattering are found in the small energy and/or small impact
      parameter scattering regime. For scattering off a classical 2D hydrogen atom
      different phenomena such as ionization, exchange of particles, and inelastic
      scattering can occur. A scattering regime diagram is constructed as function of
      the impact parameter (b) and the initial velocity (v) of the incoming particle.
      In a small regime of the (b,v) space the system exhibits chaos, which is studied
      in more detail. Analytic expressions for the scattering angle are given in the
      high impact parameter asymptotic limit.

PMID- 17500809
TI  - Short wavelength approximation of a boundary integral operator for homogeneous
      and isotropic elastic bodies.
AB  - A short wavelength approximation of a boundary integral operator for two
      dimensional isotropic and homogeneous elastic bodies is derived from first
      principles starting from the Navier-Cauchy equation. Trace formulas for
      elastodynamics are deduced connecting the eigenfrequency spectrum of an elastic
      body to the set of periodic rays where mode conversion enters as a dynamical
      feature.

PMID- 17500810
TI  - Critical ratio between the amplitudes of two overtaking solitary water waves.
AB  - In this paper, we study the critical ratio between the amplitudes of two
      overtaking solitary waves on a layer of water with uniform depth. At the center
      of encounter, the wave profile is fore-and-aft symmetric, but it could have a
      single peak or double peaks. The critical ratio separates these two regimes. At
      the critical point, the wave peak is flat with zero slope and curvature. We solve
      the full water wave problem numerically by using a fully nonlinear and highly
      dispersive Boussinesq model. The model is numerically justified to be a good
      approximation of the Euler equations for solitary waves with very large
      amplitude. For small amplitude water waves, our calculated critical ratio reduces
      to the well-known result of 3 predicted by the Korteweg-de Vries equation, a
      weakly nonlinear and weakly dispersive model. For large amplitude water waves,
      the nonlinear effect is significant; we find that the critical ratio deviates
      significantly from 3. For water waves with very high amplitude, e.g., 0.6
      relative wave height, the critical ratio could be as large as 4. Our result
      suggests that higher-order nonlinear and dispersive effects are important when
      modeling the strong interaction between large amplitude water waves.

PMID- 17500811
TI  - Fibonacci-like photonic structure for femtosecond pulse compression.
AB  - The compression of femtosecond laser pulses by linear quasiperiodic and periodic
      photonic multilayer structures is studied both experimentally and theoretically.
      We compare the compression performance of a Fibonacci and a periodic structure
      with similar total thickness and the same number of layers, and find the
      performance to be higher in the Fibonacci case, as predicted by numerical
      simulation. This compression enhancement takes place due to the larger group
      velocity dispersion at a defect resonance of the transmission spectrum of the
      Fibonacci structure. We demonstrate that the Fibonacci structure with the
      thickness of only 2.8 microm can compress a phase-modulated laser pulse by up to
      30%. The possibility for compression of laser pulses with different
      characteristics in a single multilayer is explored. The operation of the
      compressor in the reflection regime has been modeled, and we show numerically
      that the reflected laser pulse is subjected to real compression: not only does
      its duration decrease but also its amplitude rises.

PMID- 17500812
TI  - Acoustic beam invariants.
AB  - Transversely finite sound beams traveling in fluid media with negligible viscous
      damping and scattering have seven quantities constant along the length of the
      beam. The simplest of these is the cycle-averaged momentum per unit length of the
      beam. The seven constant quantities are proved to be invariants from conservation
      laws. An angular momentum flux density tensor is introduced, in the formulation
      of conservation of angular momentum. Examples of the invariants are given, for
      approximate solutions of the wave equation (Gaussian beams), and for a set of
      exact solutions (generalized Bessel beams).

PMID- 17500813
TI  - Kink dynamics in spatially inhomogeneous media: the role of internal modes.
AB  - The phenomenon of length-scale competition in soliton-bearing equations perturbed
      by spatially dependent terms [A. Sanchez and A. R. Bishop, SIAM Rev. 40, 579
      (1998)] is analyzed from a general viewpoint. We show that the perturbation gives
      rise to an effective potential for solitons, which consists of wells and
      barriers. We calculate the effect of these potential features on the solitons,
      establishing a direct relationship between the maxima, minima, and curvature of
      the potential with soliton deformations. When the typical wavelength of the
      perturbation is of the order of the soliton width, these deformations are seen to
      correspond to the excitation of shape modes and can lead to the dissipation of
      the soliton kinetic energy and, further, to the impossibility of soliton
      propagation. Thus, we demonstrate that the mechanism for length-scale competition
      is related to changes in the dynamics of the internal modes. We study different
      examples where the perturbation is introduced parametrically and
      nonparametrically to make it clear that our results apply to a wide class of
      equations.

PMID- 17500814
TI  - Solution of the reduced anisotropic Maxwell-Bloch equations by using the Riemann
      Hilbert problem.
AB  - We develop a method of solution for recently found integrable system of the
      reduced Maxwell-Bloch equations with two components of polarization and with an
      anisotropic dipole momentum by using the appropriate modification of the inverse
      scattering transform. The method is based on solution of the Riemann-Hilbert
      problem with taking into account symmetry properties of corresponding fundamental
      solutions. We show that these symmetries lead to some particular forms of the
      inverse scattering transform equations which may be used for finding as soliton
      type as radiation-type solutions.

PMID- 17500815
TI  - Transverse-average field approach for the characterization of thin metamaterial
      slabs.
AB  - The objective of this work is to investigate in which circumstances the
      scattering of electromagnetic waves by a thin metamaterial slab can be
      characterized using known effective parameters of the associated unbounded
      periodic bulk medium. It is proved that the classical approach or classical
      boundary conditions may become less accurate or incomplete if the size of
      inclusions is not significantly smaller than the wavelength. To circumvent this
      problem we demonstrate that the interaction of waves with metamaterial structures
      may in many cases with practical interest be conveniently described using a
      transverse averaged-field technique, and that this approach can be very accurate
      even for wide incident angles, evanescent waves, and for large and moderately
      large wavelengths.

PMID- 17500816
TI  - Terahertz plasmonic composites.
AB  - The dielectric response of a polymer matrix composite can be substantially
      modified and tuned within a broad frequency band by integrating within the
      material an artificial plasmon medium composed of periodically distributed, very
      thin, electrically conducting wires. In the microwave regime, such
      plasmon/polymer composites have been studied analytically, computationally, and
      experimentally. This work reports the design, fabrication, and characterization
      of similar composites for operation at terahertz frequencies. Such composites
      require significant reduction in the thickness and spacing of the wires. We used
      numerical modeling to design artificial effective plasmonic media with turn-on
      frequencies in the terahertz range. Prototype samples were produced by
      lithographically embedding very thin gold strips into a PDMS
      [poly(dimethylsiloxane)] matrix. These samples were characterized with a Fourier
      transform infrared interferometer using the frequency-dependent transmission and
      Kramers-Kronig relations to determine the electromagnetic properties. We report
      the characterization results for a sample, demonstrating excellent agreement
      between theory, computer design, and experiment. To our knowledge this is the
      first demonstration of the possibility of creating composites with tuned
      dielectric response at terahertz frequencies.

PMID- 17500817
TI  - Thermal diffusion of solitons on anharmonic chains with long-range coupling.
AB  - We extend our studies of thermal diffusion of nontopological solitons to
      anharmonic Fermi-Pasta-Ulam-type chains with additional long-range couplings. The
      observed superdiffusive behavior in the case of nearest-neighbor interaction
      turns out to be the dominating mechanism for the soliton diffusion on chains with
      long-range interactions. Using a collective variable technique in the framework
      of a variational analysis for the continuum approximation of the chain, we derive
      a set of stochastic integrodifferential equations for the collective variables
      (CVs) soliton position and the inverse soliton width. This set can be reduced to
      a statistically equivalent set of Langevin-type equations for the CV, which
      shares the same Fokker-Planck equation. The solution of the Langevin set and the
      Langevin dynamics simulations of the discrete system agree well and demonstrate
      that the variance of the soliton increases stronger than linearly with time
      (superdiffusion). This result for the soliton diffusion on anharmonic chains with
      long-range interactions reinforces the conjecture that superdiffusion is a
      generic feature of nontopological solitons.

PMID- 17500818
TI  - Breakup of a multisoliton state of the linearly damped nonlinear Schrodinger
      equation.
AB  - We address the breakup (splitting) of multisoliton solutions of the nonlinear
      Schrodinger equation (NLSE), occurring due to linear loss. Two different
      approaches are used for the study of the splitting process. The first one is
      based on the direct numerical solution of the linearly damped NLSE and the
      subsequent analysis of the eigenvalue drift for the associated Zakharov-Shabat
      spectral problem. The second one involves the multisoliton adiabatic perturbation
      theory applied for studying the evolution of the solution parameters, with the
      linear loss taken as a small perturbation. We demonstrate that in the case of
      strong nonadiabatic loss the evolution of the Zakharov-Shabat eigenvalues can be
      quite nontrivial. We also demonstrate that the multisoliton breakup can be
      correctly described within the framework of the adiabatic perturbation theory and
      can take place even due to small linear loss. Eventually we elucidate the
      occurrence of the splitting and its dependence on the phase mismatch between the
      solitons forming a two-soliton bound state.

PMID- 17500819
TI  - Phase fluctuations of linearly chirped solitons in a noisy optical fiber channel
      with varying dispersion, nonlinearity, and gain.
AB  - The phase fluctuations of arbitrarily nonlinearity- and dispersion-managed
      solitons propagating in a noisy fiber channel are studied both analytically and
      numerically. We begin by discussing the stability problem of such linearly
      chirped solitons with a full linear stability analysis. It is shown that these
      sophisticated solitons possess an enhanced stability against perturbations and
      therefore hold promise for applications in optical telecommunications. We then
      make an approach to the phase statistics of these solitons, which stems from an
      inevitable random walk in phase evolutions due to amplified spontaneous emission
      noise. By using the variational approach together with impulse-response (Green)
      functions, an elegant closed-form expression for the phase variance is derived
      based on an unconstrained self-similar soliton ansatz in which the effect of
      chirp fluctuations has been critically taken into account as well as the
      dispersive and nonlinear effects. An inspection of the intriguing subtleties of
      the interplay among these effects reveals that the chirp fluctuations effect does
      play an important role in the control of nonlinear phase noise via fiber
      dispersion, independently of whether the input solitons are initially chirped or
      not. Our analytical result also offers many possibilities of optimally
      manipulating nonlinear phase noise with engineered fiber parameters that may lead
      to the steady pulse propagation, broadening, or compression under favorable
      parametric conditions. Last, we demonstrate our result by several convincible
      examples and show an excellent agreement between analytical predictions and
      numerical simulations.

PMID- 17500820
TI  - Physics of symplectic integrators: perihelion advances and symplectic corrector
      algorithms.
AB  - Symplectic integrators evolve dynamical systems according to modified
      Hamiltonians whose error terms are also well-defined Hamiltonians. The error of
      the algorithm is the sum of each error Hamiltonian's perturbation on the exact
      solution. When symplectic integrators are applied to the Kepler problem, these
      error terms cause the orbit to precess. In this work, by developing a general
      method of computing the perihelion advance via the Laplace-Runge-Lenz vector even
      for nonseparable Hamiltonians, I show that the precession error in symplectic
      integrators can be computed analytically. It is found that at leading order, each
      paired error Hamiltonians cause the orbit to precess oppositely by exactly the
      same amount after each period. Hence, symplectic corrector, or process
      integrators, which have equal coefficients for these paired error terms, will
      have their precession errors cancel at that order after each period. With the use
      of correctable algorithms, both the energy and precession error are of effective
      order n+2 where n is the nominal order of the algorithm. Thus the physics of
      symplectic integrators determines the optimal algorithm for integrating long-time
      periodic motions.

PMID- 17500821
TI  - Mesoscopic predictions of the effective thermal conductivity for microscale
      random porous media.
AB  - A mesoscopic numerical tool has been developed in this study for predictions of
      the effective thermal conductivities for microscale random porous media. To solve
      the energy transport equation with complex multiphase porous geometries, a
      lattice Boltzmann algorithm has been introduced to tackle the conjugate heat
      transfer among different phases. With boundary conditions correctly chosen, the
      algorithm has been initially validated by comparison with theoretical solutions
      for simpler cases and with the existing experimental data. Furthermore, to
      reflect the stochastic phase distribution characteristics of most porous media, a
      random internal morphology and structure generation-growth method, termed the
      quartet structure generation set (QSGS), has been proposed based on the
      stochastic cluster growth theory for generating more realistic microstructures of
      porous media. Thus by using the present lattice Boltzmann algorithm along with
      the structure generating tool QSGS, we can predict the effective thermal
      conductivities of porous media with multiphase structure and stochastic complex
      geometries, without resorting to any empirical parameters determined case by
      case. The methodology has been applied in this contribution to several two- and
      three-phase systems, and the results agree well with published experimental data,
      thus demonstrating that the present method is rigorous, general, and robust.
      Besides conventional porous media, the present approach is applicable in dealing
      with other multiphase mixtures, alloys, and multicomponent composites as well.

PMID- 17500822
TI  - Quantum annealing of an Ising spin-glass by Green's function Monte Carlo.
AB  - We present an implementation of quantum annealing (QA) via lattice Green's
      function Monte Carlo (GFMC), focusing on its application to the Ising spin glass
      in transverse field. In particular, we study whether or not such a method is more
      effective than the path-integral Monte Carlo- (PIMC) based QA, as well as
      classical simulated annealing (CA), previously tested on the same optimization
      problem. We identify the issue of importance sampling, i.e., the necessity of
      possessing reasonably good (variational) trial wave functions, as the key point
      of the algorithm. We performed GFMC-QA runs using such a Boltzmann-type trial
      wave function, finding results for the residual energies that are qualitatively
      similar to those of CA (but at a much larger computational cost), and definitely
      worse than PIMC-QA. We conclude that, at present, without a serious effort in
      constructing reliable importance sampling variational wave functions for a
      quantum glass, GFMC-QA is not a true competitor of PIMC-QA.

PMID- 17500823
TI  - Thermal lattice Boltzmann equation for low Mach number flows: decoupling model.
AB  - A lattice Boltzmann model is proposed for solving low Mach number thermal flows
      with viscous dissipation and compression work in the double-distribution-function
      framework. A distribution function representing the total energy is defined based
      on a single velocity distribution function, and its evolution equation is derived
      from the continuous Boltzmann equation. A lattice Boltzmann equation model with
      clear physics and a simple structure is then obtained from a kinetic model for
      the decoupled hydrodynamic and energy equations. The model is tested by
      simulating a thermal Poiseuille flow and natural convection in a square cavity,
      and it is found that the numerical results agree well with the analytical
      solutions and/or the data reported in previous studies.

PMID- 17500824
TI  - Automatic algorithm for monotone trend removal.
AB  - The available numerical algorithms for trend removal require a direct subjective
      intervention in choosing critical parameters. In this paper an algorithm is
      presented, which needs no initial subjective assumptions. Monotone trends are
      approximated by piecewise linear curves obtained by dividing into subintervals
      the signal values interval, not the time interval. The slope of each linear
      segment of the estimated trend is proportional to the average one-step
      displacement of the signal values included into the corresponding subinterval.
      The evaluation of the trend removal is performed on statistical ensembles of
      artificial time series with the random component given by realizations of
      autoregressive of order one stochastic processes or by fractional Brownian
      motions. The accuracy of the algorithm is compared with that of two well-tested
      methods: polynomial fitting and a nonparametric method based on moving average.
      For stationary noise the results of the algorithm are slightly better, but for
      nonstationary noise the preliminary results indicate that the polynomial fitting
      has the best accuracy. As a verification on a real time series, the time periods
      with monotone variation of global average temperature over the last 1800years are
      established. The removal of a nonmonotone trend is also briefly discussed.

PMID- 17500825
TI  - Alternative method to construct equilibrium distribution functions in lattice
      Boltzmann method simulation of inviscid compressible flows at high Mach number.
AB  - A method is proposed to construct an equilibrium density distribution function in
      the simulation of compressible flows at high Mach number by the lattice-Boltzmann
      method. In this method, the conventional Maxwellian distribution function is
      replaced by a circular function which is very simple and satisfies all needed
      statistical relations to recover the compressible Navier-Stokes equations. The
      circular function is then distributed to the lattice velocity directions by
      Lagrangian interpolation in such a way that all the needed statistical relations
      are exactly satisfied when the integral in the phase space is replaced by the
      summation in the context of the lattice-Boltzmann (LB) method. In this framework,
      the equilibrium distribution functions and the associated lattice velocity model
      can be derived naturally without assuming specific forms. Two LB models with
      adjustable specific heat ratio, respectively, for one-dimensional (1D) and two
      dimensional (2D) compressible flows are shown in the paper. Some test cases of
      compressible flows with strong shock waves are simulated to validate the present
      approach. Excellent results are obtained. Note that in the simulation, the total
      variation diminishing (TVD) scheme was used to capture the discontinuity with
      coarse mesh.

PMID- 17500826
TI  - Accurate numerical solutions of the time-dependent Schrodinger equation.
AB  - We present a generalization of the often-used Crank-Nicolson (CN) method of
      obtaining numerical solutions of the time-dependent Schrodinger equation. The
      generalization yields numerical solutions accurate to order (Deltax)2r-1 in space
      and (Deltat)2M in time for any positive integers r and M, while CN employ r=M=1.
      We note dramatic improvement in the attainable precision (circa ten or greater
      orders of magnitude) along with several orders of magnitude reduction of
      computational time. The improved method is shown to lead to feasible studies of
      coherent-state oscillations with additional short-range interactions, wave-packet
      scattering, and long-time studies of decaying systems.

PMID- 17500827
TI  - Lattice-based Monte Carlo method for telechelic chain molecules.
AB  - We present a Monte Carlo (MC) scheme that makes it possible to perform efficient
      simulations of dense systems of self-avoiding polymers on a lattice. We show that
      the method is particularly useful to simulate dense systems of polymers with
      functionalized end groups. We compare the efficiency of the scheme with the
      configurational bias MC method and indicate the regime where the present approach
      is the method of choice.

PMID- 17500828
TI  - Simulating time harmonic flows with the lattice Boltzmann method.
AB  - We simulate time harmonic flows by the lattice Boltzmann method. We propose a
      general scheme to choose simulation parameters, under the constraints of fixed
      Reynolds and Womersley numbers, and with a specified simulation error. Under
      these constraints parameters are chosen to minimize the execution time. Numerical
      stability is studied in a range of Reynolds and Womersley numbers. As an example
      of time harmonic flow simulations, results of blood flow in a human abdominal
      aorta are presented.

PMID- 17500829
TI  - Multigrid contact detection method.
AB  - Contact detection is a general problem of many physical simulations. This work
      presents a O(N) multigrid method for general contact detection problems (MGCD).
      The multigrid idea is integrated with contact detection problems. Both the time
      complexity and memory consumption of the MGCD are O(N). Unlike other methods,
      whose efficiencies are influenced strongly by the object size distribution, the
      performance of MGCD is insensitive to the object size distribution. We compare
      the MGCD with the no binary search (NBS) method and the multilevel boxing method
      in three dimensions for both time complexity and memory consumption. For objects
      with similar size, the MGCD is as good as the NBS method, both of which
      outperform the multilevel boxing method regarding memory consumption. For objects
      with diverse size, the MGCD outperform both the NBS method and the multilevel
      boxing method. We use the MGCD to solve the contact detection problem for a
      granular simulation system based on the discrete element method. From this
      granular simulation, we get the density property of monosize packing and binary
      packing with size ratio equal to 10. The packing density for monosize particles
      is 0.636. For binary packing with size ratio equal to 10, when the number of
      small particles is 300 times as the number of big particles, the maximal packing
      density 0.824 is achieved.

PMID- 17500830
TI  - Stability and stabilization of the lattice Boltzmann method.
AB  - We revisit the classical stability versus accuracy dilemma for the lattice
      Boltzmann methods (LBM). Our goal is a stable method of second-order accuracy for
      fluid dynamics based on the lattice Bhatnager-Gross-Krook method (LBGK). The LBGK
      scheme can be recognized as a discrete dynamical system generated by free flight
      and entropic involution. In this framework the stability and accuracy analysis
      are more natural. We find the necessary and sufficient conditions for second
      order accurate fluid dynamics modeling. In particular, it is proven that in order
      to guarantee second-order accuracy the distribution should belong to a
      distinguished surface--the invariant film (up to second order in the time step).
      This surface is the trajectory of the (quasi)equilibrium distribution surface
      under free flight. The main instability mechanisms are identified. The simplest
      recipes for stabilization add no artificial dissipation (up to second order) and
      provide second-order accuracy of the method. Two other prescriptions add some
      artificial dissipation locally and prevent the system from loss of positivity and
      local blowup. Demonstration of the proposed stable LBGK schemes are provided by
      the numerical simulation of a one-dimensional (1D) shock tube and the unsteady 2D
      flow around a square cylinder up to Reynolds number Re approximately 20,000.

PMID- 17500831
TI  - Entropic lattice Boltzmann representations required to recover Navier-Stokes
      flows.
AB  - There are two disparate formulations of the entropic lattice Boltzmann scheme:
      one of these theories revolves around the analog of the discrete Boltzmann H
      function of standard extensive statistical mechanics, while the other revolves
      around the nonextensive Tsallis entropy. It is shown here that it is the
      nonenforcement of the pressure tensor moment constraints that lead to
      extremizations of entropy resulting in Tsallis-like forms. However, with the
      imposition of the pressure tensor moment constraint, as is fundamentally
      necessary for the recovery of the Navier-Stokes equations, it is proved that the
      entropy function must be of the discrete Boltzmann form. Three-dimensional
      simulations are performed which illustrate some of the differences between
      standard lattice Boltzmann and entropic lattice Boltzmann schemes, as well as the
      role played by the number of phase-space velocities used in the discretization.

PMID- 17500832
TI  - Reptational dynamics in dissipative particle dynamics simulations of polymer
      melts.
AB  - Understanding the fundamental properties of polymeric liquids remains a challenge
      in materials science and soft matter physics. Here, we present a simple and
      computationally efficient criterion for topological constraints, i.e.,
      uncrossability of chains, in polymeric liquids using the dissipative particle
      dynamics (DPD) method. No new length scales or forces are added. To demonstrate
      that this approach really prevents chain crossings, we study a melt of linear
      homopolymers. We show that for short chains the model correctly reproduces Rouse
      like dynamics whereas for longer chains the dynamics becomes reptational as the
      chain length is increased--something that is not attainable using standard DPD or
      other coarse-grained soft potential methods.

PMID- 17500833
TI  - Power-law distributions for the areas of the basins of attraction on a potential
      energy landscape.
AB  - Energy landscape approaches have become increasingly popular for analyzing a wide
      variety of chemical physics phenomena. Basic to many of these applications has
      been the inherent structure mapping, which divides up the potential energy
      landscape into basins of attraction surrounding the minima. Here, we probe the
      nature of this division by introducing a method to compute the basin area
      distribution and applying it to some archetypal supercooled liquids. We find that
      this probability distribution is a power law over a large number of decades with
      the lower-energy minima having larger basins of attraction. Interestingly, the
      exponent for this power law is approximately the same as that for a high
      dimensional Apollonian packing, providing further support for the suggestion that
      there is a strong analogy between the way the energy landscape is divided into
      basins, and the way that space is packed in self-similar, space-filling
      hypersphere packings, such as the Apollonian packing. These results suggest that
      the basins of attraction provide a fractal-like tiling of the energy landscape,
      and that a scale-free pattern of connections between the minima is a general
      property of energy landscapes.

PMID- 17500834
TI  - Accelerator dynamics of a fractional kicked rotor.
AB  - It is shown that the Weyl fractional derivative can quantize an open system. A
      fractional kicked rotor is studied in the framework of the fractional Schrodinger
      equation. The system is described by the non-Hermitian Hamiltonian by virtue of
      the Weyl fractional derivative. Violation of space symmetry leads to acceleration
      of the orbital momentum. Quantum localization saturates this acceleration, such
      that the average value of the orbital momentum can be a direct current and the
      system behaves like a ratchet. The classical counterpart is a nonlinear kicked
      rotor with absorbing boundary conditions.

PMID- 17500835
TI  - Experimental investigation of electric field distributions in a chaotic three
      dimensional microwave rough billiard.
AB  - We present an experimental study of the electric field distributions EN of a
      three-dimensional (3D) microwave chaotic rough billiard with the translational
      symmetry. The translational symmetry means that the cross section of the billiard
      is invariant under translation along the z direction. The 3D electric field
      distributions were measured up to the level number N=489. In this way the
      experimental spatial correlation functions
      CN,p(x,s)proportional<EN,p(x+1/2s)EN,p*(x-1/2s)> were found and compared with the
      theoretical ones. The experimental results for higher two-dimensional level
      number Nperpendicular appeared to be in good agreement with the theoretical
      predictions.

PMID- 17500836
TI  - Synchronization threshold of a coupled time-delay system.
AB  - The synchronization threshold in the general form of a one-way coupled time
      delayed system is discussed. Based on the Krasovskii-Lyapunov theory, the
      deduction process and the application range of the synchronization threshold are
      given. In addition, a misuse of the synchronization threshold is presented and is
      illustrated by an example.

PMID- 17500838
TI  - Accurate modeling of the optical properties of left-handed media using a finite
      difference time-domain method.
AB  - This paper contains an important message regarding the numerical modeling of left
      handed media (LHM) using the finite-difference time-domain (FDTD) method which
      remains at the moment one of the main techniques used in studies of these exotic
      materials. It is shown that conventional implementation of the dispersive FDTD
      method leads to an inaccurate description of evanescent waves in the LHM. This
      defect can be corrected using spatial averaging at the interfaces. However, a
      number of results obtained using the conventional FDTD method have to be
      reconsidered. For instance, accurate simulation of subwavelength imaging by the
      finite-sized slabs of left-handed media does not reveal the cavity effect
      reported by Chen [Phys. Rev. Lett. 92, 107404 (2004)]. Hence the finite
      transverse dimension of LHM slabs does not have significant effects on the
      subwavelength image quality, contrary to previous assertions.

PMID- 17500837
TI  - Anomalous oscillations in the spectra of light backscattered by inhomogeneous
      microparticles.
AB  - We report anomalous oscillatory features in the spectra of cross-polarized
      backscattered light from inhomogeneous dielectric microparticles. Numerical
      experiments based on the finite-difference-time-domain method demonstrate that
      cross-polarized backscattered spectra exhibit oscillation frequencies with two a
      priori surprising features. First, the oscillation frequencies decrease as the
      correlation length (Lc) of the particle's refractive index increases. Second,
      high-frequency oscillations exist even for Lc much smaller than the optical
      wavelength. These findings are exactly opposite to what is observed in co
      polarized backscattering spectra, and are not expected from conventional optical
      scattering theory. We explain this anomalous behavior by examining the path
      length distributions of the backscattered photons in the cross polarization.

PMID- 17500839
TI  - Perturbative analytical treatment of adiabatically moderated soliton self
      frequency shift.
AB  - We provide a perturbative analytical treatment of the soliton self-frequency
      shift (SSFS) in optical fibers including the main physical mechanisms limiting
      the SSFS, such as the high-order dispersion, the wavelength dependence of the
      effective mode area, and optical loss. We use this approach to estimate the
      frequency shift of a soliton with adiabatically varying local parameters and
      compare this estimate with the results of numerical simulations for SSFS in
      photonic-crystal fibers. This comparison shows that, in many situations of
      practical interest, the proposed approach can adequately predict important
      tendencies of SSFS, and allows a fair estimation of characteristic length scales
      for the mechanisms limiting the SSFS.

PMID- 17500840
TI  - Comment on "calculation of electromagnetic field components for a fundamental
      Gaussian beam".
AB  - In this Comment, we point out that the ninth-order expressions for
      electromagnetic fields for a fundamental Gaussian beam given by Wang and Webb
      [Phys. Rev. E 72, 046501 (2005)] are incorrect. The correct expressions for the
      electromagnetic field components up to ninth order are given.

PMID- 17500842
TI  - Comment on "exact solutions of the derivative nonlinear Schrodinger equation for
      a nonlinear transmission line".
AB  - In a recent article Kengne and Liu [Phys. Rev. E 73, 026603 (2006)] have
      presented a number of exact elliptic solutions for a derivative nonlinear
      Schrodinger equation. It is the aim of this Comment to point out that all these
      solutions given in Secs. II and III of this article (referred to as KL in the
      following) are subcases of the general solution of Eq. (KL.9). Conditions for the
      parameters A-E of the solutions given by Kengne and Liu can be found from general
      conditions for solitary and periodic elliptic solutions as shown in the
      following. Positive and bounded solutions can be found by considering the phase
      diagram. Therefore, the comment of Kengne and Liu that "we find its particular
      positive bounded solutions" can be specified.

PMID- 17500843
TI  - Long-term correlations in stochastic systems with extended time-delayed feedback.
AB  - The effects of a feedback with multiple time delays on noise-induced dynamics are
      studied in a nonlinear system close to the Hopf instability. We show analytically
      and numerically that such a feedback creates two distinct time scales, which can
      be tuned independently by the feedback parameters. In this way, the coherence of
      noise-induced oscillations can be drastically improved, and an arbitrarily large
      correlation of oscillations can be achieved without inducing a bifurcation. This
      opens up new perspectives for control of stochastic dynamical systems.

PMID- 17500844
TI  - Ergodicity of a thermostat family of the Nose-Hoover type.
AB  - One-variable thermostats are studied as a generalization of the Nose-Hoover
      method, which is aimed at achieving Gibbs' canonical distribution while
      conserving the time reversibility. A condition for equations of motion for the
      system with the thermostats is derived in the form of a partial differential
      equation. Solutions of this equation constitute a family of thermostats including
      the Nose-Hoover method as the minimal solution. It is shown that the one-variable
      thermostat coupled with the one-dimensional harmonic oscillator loses its
      ergodicity with large enough relaxation time. The present result suggests that
      multivariable thermostats are required to assure the ergodicity and to work as a
      heat bath.

PMID- 17500845
TI  - Rectification of the lateral Casimir force in a vibrating noncontact rack and
      pinion.
AB  - The nonlinear dynamics of a cylindrical pinion that is kept at a distance from a
      vibrating rack is studied, and it is shown that the lateral Casimir force between
      the two corrugated surfaces can be rectified. The effects of friction and
      external load are taken into account, and it is shown that the pinion can do work
      against loads of up to a critical value, which is set by the amplitude of the
      lateral Casimir force. We present a phase diagram for the rectified motion that
      could help its experimental investigations, as the system exhibits a chaotic
      behavior in a large part of the parameter space.

PMID- 17500846
TI  - Short-time critical dynamics and aging phenomena in the two-dimensional XY model.
AB  - With Monte Carlo methods, we simulate dynamic relaxation processes of the two
      dimensional XY model at the Berezinskii-Kosterlitz-Thouless phase transition
      temperature and below, starting from both ordered and disordered initial states.
      The two-time correlation function A(t',t) is measured, and aging phenomena are
      investigated. The power-law correction in the spatial correlation length xi(t)
      for relaxation with an ordered initial state and the logarithmic correction for
      relaxation with a disordered initial state are carefully analyzed. The scaling
      functions of A(t',t) are then extracted.

PMID- 17500847
TI  - Exact solution of close-packed dimers on the kagome lattice.
AB  - It is well known that exact enumerations of close-packed dimers can be carried
      out for two-dimensional lattices. While details of results are now known for most
      lattices, due to the unique nature of the lattice structure, there has been no
      complete analysis for the kagome lattice. Here we derive the close-form
      expression (13) ln(4xyz) for the free energy of close-packed dimers on the kagome
      lattice, where x , y , and z are dimer weights. We use two different approaches:
      the Kasteleyn method of evaluating a Pfaffian and an alternative vertex model
      formulation. Both methods lead to the same final expression. The correlation
      function between two dimers at a distance equal or greater than two lattice
      spacings is found to vanish identically.

PMID- 17500848
TI  - Central limit behavior of deterministic dynamical systems.
AB  - We investigate the probability density of rescaled sums of iterates of
      deterministic dynamical systems, a problem relevant for many complex physical
      systems consisting of dependent random variables. A central limit theorem (CLT)
      is valid only if the dynamical system under consideration is sufficiently mixing.
      For the fully developed logistic map and a cubic map we analytically calculate
      the leading-order corrections to the CLT if only a finite number of iterates is
      added and rescaled, and find excellent agreement with numerical experiments. At
      the critical point of period doubling accumulation, a CLT is not valid anymore
      due to strong temporal correlations between the iterates. Nevertheless, we
      provide numerical evidence that in this case the probability density converges to
      a q -Gaussian, thus leading to a power-law generalization of the CLT. The above
      behavior is universal and independent of the order of the maximum of the map
      considered, i.e., relevant for large classes of critical dynamical systems.

PMID- 17500849
TI  - Domain-size distribution in a Poisson-Voronoi nucleation and growth
      transformation.
AB  - We present an analytical result for the evolution of the domain-size distribution
      during the growth of simultaneously nucleated domains. The final stage of this
      transformation is the well-known Poisson-Voronoi tessellation. The method can be
      easily extended to the calculation of the probability distribution of any other
      geometric characteristic. As far as we know, it is the first time that an exact
      result is given for this classic system.

PMID- 17500850
TI  - Thermophoresis of microemulsion droplets: size dependence of the Soret effect.
AB  - Thermophoresis, akin to thermal diffusion in simple fluid mixtures, consists of
      particle drift induced by a temperature gradient. Notwithstanding its practical
      interest, the dependence of thermophoretic effects on particle size R is still
      theoretically and experimentally debated. By performing measurements of water-in
      oil microemulsion droplets with tunable size, we show that the thermal diffusion
      coefficient, at least for a suspension of small particles in a nonpolar solvent,
      does not appreciably depend on R .

PMID- 17500851
TI  - Stripes, clusters, and nonequilibrium ordering for bidisperse colloids with
      repulsive interactions.
AB  - We show that two-dimensional bidisperse assemblies of colloids with strictly
      repulsive interactions exhibit stripe, cluster, and partially crystallized states
      when driven over a quenched random substrate. The nonequilibrium states on a
      substrate are significantly more ordered than equilibrium states both with and
      without substrates. A minimum substrate strength is necessary to induce the
      nonequilibrium pattern formation. Our results suggest that a combination of
      driving and quenched disorder offers a new approach to controlling pattern
      formation in colloid mixtures.

PMID- 17500852
TI  - Dynamics in inhomogeneous liquids and glasses via the test particle limit.
AB  - We show that one may view the self-part and the distinct-part of the van Hove
      dynamic correlation function of a simple fluid as the one-body density
      distributions of a binary mixture that evolve in time according to dynamical
      density functional theory. For a test case of soft-core Brownian particles the
      theory yields results for the van Hove function that agree quantitatively with
      those of our Brownian dynamics computer simulations. At sufficiently high
      densities the free energy landscape underlying the dynamics exhibits a barrier as
      a function of the mean particle displacement, shedding new light on the nature of
      glass formation. For hard spheres confined between parallel planar walls the
      barrier height oscillates in phase with the local density, implying that the
      mobility is maximal between layers, which should be experimentally observable in
      confined colloidal dispersions.

PMID- 17500853
TI  - Dynamic electric polarization of nematic liquid crystals subjected to a shear
      flow.
AB  - The effect of coupling between the dipole moment and the orientation is explored
      based on a relaxation equation for the second rank alignment tensor
      characterizing the molecular order in liquid crystals and a corresponding
      equation for the electric polarization. The orientational dynamics leads to a
      time dependence of the electric polarization. We propose a possibility to measure
      these effects via the resulting magnetic fields of the magnitude |B|
      approximately equal to 10(-9)T . Furthermore, the presence of the electric
      polarization modifies the orientational dynamics as demonstrated in solution
      phase diagrams.

PMID- 17500854
TI  - Icosahedral packing of polymer-tethered nanospheres and stabilization of the
      gyroid phase.
AB  - We present results of simulations that predict the phases formed by the self
      assembly of model nanospheres functionalized with a single polymer "tether,"
      including double gyroid, perforated lamella, and crystalline bilayer phases. We
      show that microphase separation of the immiscible tethers and nanospheres causes
      confinement of the nanoparticles, which promotes local icosahedral packing that
      in turn stabilizes the gyroid. We present a new metric for determining the local
      arrangement of particles based on spherical harmonic "fingerprints," which we use
      to quantify the extent of icosahedral ordering.

PMID- 17500855
TI  - Dynamics of DNA tumbling in shear to rotational mixed flows: pathways and
      periods.
AB  - The tumbling dynamics of DNA have been examined via experiments and Brownian
      dynamics (BD) simulations in mixed flows that vary from pure shear to pure
      rotation. In shear, tumbling pathways and periods agree well with earlier
      studies; in rotation-dominated flows, a new tumbling pathway is identified and
      experimentally observed. Based on these results, we have developed robust scaling
      laws for DNA tumbling in both shear and rotational flows and have found a
      critical flow-type parameter for transition from the shearlike flow regime to the
      rotation-dominated one.

PMID- 17500856
TI  - Softening of the stiffness of bottle-brush polymers by mutual interaction.
AB  - We study bottle-brush macromolecules in a good solvent by small-angle neutron
      scattering (SANS), static light scattering (SLS), and dynamic light scattering
      (DLS). These polymers consist of a linear backbone to which long side chains are
      chemically grafted. The backbone contains about 1600 monomer units (weight
      average) and every second monomer unit carries side chains with approximately 60
      monomer units. The SLS and SANS data extrapolated to infinite dilution lead to
      the form factor of the polymer that can be described in terms of a wormlike chain
      with a contour length of 380 nm and a persistence length of 17.5 nm. An analysis
      of the DLS data confirms these model parameters. The scattering intensities taken
      at finite concentration can be modeled using the polymer reference interaction
      site model. It reveals a softening of the bottle-brush polymers caused by their
      mutual interaction. We demonstrate that the persistence decreases from 17.5 nm
      down to 5 nm upon increasing the concentration from dilute solution to the
      highest concentration (40.59 gl) under consideration. The observed softening of
      the chains is comparable to the theoretically predicted decrease of the
      electrostatic persistence length of linear polyelectrolyte chains at finite
      concentrations.

PMID- 17500857
TI  - Model for dynamical coherence in thin films of self-propelled microorganisms.
AB  - Concentrated bacterial suspensions spontaneously develop transient spatiotemporal
      patterns of coherent locomotion whose correlation lengths greatly exceed the size
      of individual organisms. Continuum models have indicated that a state of uniform
      swimming order is linearly unstable at finite wavelengths, but have not addressed
      the nonlinear dynamics of the coherent state, with its biological implications
      for mixing, transport, and intercellular communication. We investigate a specific
      model incorporating hydrodynamic interactions in thin-film geometries and show by
      numerical studies that it displays large scale persistently recurring vortices,
      as actually observed.

PMID- 17500859
TI  - Barrier crossing driven by Levy noise: universality and the role of noise
      intensity.
AB  - We study the barrier crossing of a particle driven by white symmetric Levy noise
      of index alpha and intensity D for three different generic types of potentials:
      (a) a bistable potential, (b) a metastable potential, and (c) a truncated
      harmonic potential. For the low noise intensity regime we recover the previously
      proposed algebraic dependence on D of the characteristic escape time, T_{esc}
      approximately C(alpha)D;{mu(alpha)} , where C(alpha) is a coefficient. It is
      shown that the exponent mu(alpha) remains approximately constant, mu
      approximately 1 for 0<alpha<2 ; at alpha=2 the power-law form of T_{esc} changes
      into the known exponential dependence on 1D ; it exhibits a divergencelike
      behavior as alpha approaches 2. In this regime we observe a monotonous increase
      of the escape time T_{esc} with increasing alpha (keeping the noise intensity D
      constant). The probability density of the escape time decays exponentially. In
      addition, for low noise intensities the escape times correspond to barrier
      crossing by multiple Levy steps. For high noise intensities, the escape time
      curves collapse for all values of alpha . At intermediate noise intensities, the
      escape time exhibits nonmonotonic dependence on the index alpha , while still
      retaining the exponential form of the escape time density.

PMID- 17500858
TI  - Effects of hydration water on protein methyl group dynamics in solution.
AB  - Elastic and quasielastic neutron scattering experiments have been used to
      investigate the dynamics of methyl groups in a protein-model hydrophobic peptide
      in solution. The results suggest that, when the hydrophobic side chains are
      hydrated by a single hydration water layer, the only allowed motions are confined
      and attributed to librational and rotational movement associated with the methyl
      groups. They provide unique experimental evidence that the structural and
      dynamical properties of the interfacial water strongly influence the side-chain
      dynamics and the activation of diffusive motion.

PMID- 17500860
TI  - Exact propagator for generalized Ornstein-Uhlenbeck processes.
AB  - A closed form expression for the propagator is derived, in terms of modified
      Bessel functions, for the Fokker-Planck equation for a physically important
      generalization of the Ornstein-Uhlenbeck process where the diffusion constant
      D(p) is a function of the momentum. The closed form is found for the general case
      D(p) approximately |p|(-alpha) where alpha > or =0 and leads to the standard
      Gaussian form for alpha=0 . The propagator for the specific case D(p)
      approximately |p|(-1) is used to derive analytic expressions for probability
      distributions and correlation coefficients. An exact expression is found for the
      constant of proportionality for the anomalous diffusion of the mean-square
      displacement of a particle at short times.

PMID- 17500861
TI  - Dissipation can enhance quantum effects.
AB  - Usually one finds that dissipation tends to make a quantum system more classical
      in nature. We study the effect of momentum dissipation on a quantum system. The
      momentum of the particle is coupled bi-linearly to the momenta of a harmonic
      oscillator heat bath. For a harmonic oscillator system we find that the position
      and momentum variances for momentum coupling are, respectively, identical to
      momentum and position variances for spatial friction. This implies that momentum
      coupling leads to an increase in the fluctuations in position as the temperature
      is lowered, exactly the opposite of the classical-like localization of the
      oscillator, found with spatial friction. For a parabolic barrier, momentum
      coupling causes an increase in the unstable normal mode barrier frequency, as
      compared to the lowering of the barrier frequency in the presence of purely
      spatial coupling. This increase in the frequency leads to an enhancement of the
      thermal tunneling flux, which below the crossover temperature becomes
      exponentially large. The crossover temperature between tunneling and thermal
      activation increases with momentum friction so that quantum effects in the escape
      are relevant at higher temperatures.

PMID- 17500862
TI  - Self-organizing behavior in a lattice model for co-evolution of virus and immune
      systems.
AB  - We propose a lattice model for the co-evolution of a virus population and an
      adaptive immune system. We show that, under some natural assumptions, both
      probability distribution of the virus population and the distribution of activity
      of the immune system tend during the evolution to a self-organized critical
      state.

PMID- 17500863
TI  - Size of knots in ring polymers.
AB  - We give two different, statistically consistent definitions of the length l of a
      prime knot tied into a polymer ring. In the good solvent regime the polymer is
      modeled by a self avoiding polygon of N steps on cubic lattice and l is the
      number of steps over which the knot "spreads" in a given configuration. An
      analysis of extensive Monte Carlo data in equilibrium shows that the probability
      distribution of l as a function of N obeys a scaling of the form p(l,N)
      approximately l(-c)f(l/N(D)) , with c approximately equal to 1.25 and D
      approximately equal to 1. Both D and c could be independent of knot type. As a
      consequence, the knot is weakly localized, i.e., <l> approximately N(t) , with
      t=2-c approximately equal to 0.75 . For a ring with fixed knot type, weak
      localization implies the existence of a peculiar characteristic length l(nu)
      approximately N(tnu) . In the scaling approximately N(nu) (nu approximately equal
      to 0.58) of the radius of gyration of the whole ring, this length determines a
      leading power law correction which is much stronger than that found in the case
      of unrestricted topology. The existence of this correction is confirmed by an
      analysis of extensive Monte Carlo data for the radius of gyration. The collapsed
      regime is studied by introducing in the model sufficiently strong attractive
      interactions for nearest neighbor sites visited by the self-avoiding polygon. In
      this regime knot length determinations can be based on the entropic competition
      between two knotted loops separated by a slip link. These measurements enable us
      to conclude that each knot is delocalized (t approximately equal to 1) .

PMID- 17500864
TI  - Stochastic synchronization via noise recycling.
AB  - The nonequilibrium escape dynamics in a bistable system under the influence of
      two Gaussian noises, one obtained by recycling, the other with a constant delay
      time, is shown by numerical simulation to exhibit stochastic synchronization;
      i.e., under stationary conditions, an appreciable fraction of renewal
      trajectories gets locked to the noise-recycling delay time. The conditions for
      optimal synchronization, reminiscent of stochastic resonance, are interpreted at
      any order within the framework of Kramers' theory.

PMID- 17500865
TI  - Effects of disorder on synchronization of discrete phase-coupled oscillators.
AB  - We study synchronization in populations of phase-coupled stochastic three-state
      oscillators characterized by a distribution of transition rates. We present
      results on an exactly solvable dimer as well as a systematic characterization of
      globally connected arrays of N types of oscillators (N=2,3,4) by exploring the
      linear stability of the nonsynchronous fixed point. We also provide results for
      globally coupled arrays where the transition rate of each unit is drawn from a
      uniform distribution of finite width. Even in the presence of transition rate
      disorder, numerical and analytical results point to a single phase transition to
      macroscopic synchrony at a critical value of the coupling strength. Numerical
      simulations make possible further characterization of the synchronized arrays.

PMID- 17500866
TI  - Sub-block order parameter in a driven Ising lattice gas using block distribution
      functions.
AB  - We investigate the order parameter of the standard Ising lattice gas and driven
      Ising lattice gas models. The sub-block order parameter is introduced to these
      conserved models as an order parameter using block distribution functions. We
      also introduce the sub-block order parameter of damage using the block
      distribution functions of damage. We measure the sub-block order parameters using
      the Metropolis and heat-bath rates. These order parameters work well for the non
      equilibrium-conserved model as well as the equilibrium-conserved model. We obtain
      the critical exponent of order parameter beta=1/8 for the standard Ising lattice
      gas and beta=1/2 for a driven Ising lattice gas using the Metropolis and heat
      bath rates.

PMID- 17500867
TI  - Maxwell's demon and Smoluchowski's trap door.
AB  - A simulation has been performed to reveal the detailed dynamics and statistical
      behavior of a Maxwell demon of the simplest kind, a trap door held over by a
      spring inside a box filled with gas molecules. The role of such a demon can be
      controlled by tuning Smoluchowski's fluctuations. When the demon is in thermal
      equilibrium with the rest of the system, it fails to function as designed, and
      when it is separately subjected to a thermal bath with a different temperature,
      it creates a temperature or density gradient between the two chambers of the box
      it divides. As a Maxwell demon, the trap-door device creates more readily a
      density gradient than that of temperature.

PMID- 17500868
TI  - Tests of nonuniversality and finite-size scaling for two-dimensional wetting with
      long-ranged forces.
AB  - Effective Hamiltonian models predict nonuniversal critical singularities for two
      dimensional wetting transitions with marginal long-ranged forces. We test these
      predictions by studying interfacial delocalization transitions in an infinitely
      long Ising strip, of width L (lattice spacings), with external fields that are
      long ranged and have opposite signs at each surface. Finite-size scaling suggests
      that the shift of the delocalization temperature T(c)(L) below the (semi
      infinite) wetting temperature T(w) scales as L(-1/beta(s)) with beta(s) the
      adsorption critical exponent. Density-matrix renormalization-group methods allow
      us to study the behavior of T(c)(L) for L up to several hundred lattice spacings.
      For short-ranged forces the method recovers the universal value of beta(s)=1
      known from the exact solution. While marginal long-ranged forces strongly
      influence the finite-size scaling of T(c)(L) , the extrapolated asymptotic value
      for the exponent beta(s) does not appear to confirm the predicted
      nonuniversality, but instead approaches the same universal value representative
      of systems with short-ranged forces.

PMID- 17500869
TI  - Classical evolution of fractal measures on the lattice.
AB  - We consider the classical evolution of a lattice of nonlinear coupled oscillators
      for a special case of initial conditions resembling the equilibrium state of a
      macroscopic thermal system at the critical point. The displacements of the
      oscillators define initially a fractal measure on the lattice associated with the
      scaling properties of the order parameter fluctuations in the corresponding
      critical system. Assuming a sudden symmetry breaking (quench), leading to a
      change in the equilibrium position of each oscillator, we investigate in some
      detail the deformation of the initial fractal geometry as time evolves. In
      particular, we show that traces of the critical fractal measure can be sustained
      for large times, and we extract the properties of the chain that determine the
      associated time scales. Our analysis applies generally to critical systems for
      which, after a slow developing phase where equilibrium conditions are justified,
      a rapid evolution, induced by a sudden symmetry breaking, emerges on time scales
      much shorter than the corresponding relaxation or observation time. In
      particular, it can be used in the fireball evolution in a heavy-ion collision
      experiment, where the QCD critical point emerges, or in the study of evolving
      fractals of astrophysical and cosmological scales, and may lead to determination
      of the initial critical properties of the Universe through observations in the
      symmetry-broken phase.

PMID- 17500870
TI  - Berezinskii-Kosterlitz-Thouless-like transition in the Potts model on an
      inhomogeneous annealed network.
AB  - We solve the ferromagnetic q-state Potts model on an inhomogeneous annealed
      network which mimics a random recursive graph. We find that this system has the
      inverted Berezinskii-Kosterlitz-Thouless (BKT) phase transition for any q > or =1
      , including the values q > or =3 , where the Potts model normally shows a first
      order phase transition. We obtain the temperature dependences of the order
      parameter, specific heat, and susceptibility demonstrating features typical for
      the BKT transition. We show that in the entire normal phase, both the
      distribution of a linear response to an applied local field and the distribution
      of spin-spin correlations have a critical, i.e., power-law form.

PMID- 17500871
TI  - Towards a unification of hierarchical reference theory and self-consistent
      Ornstein-Zernike approximation: analysis of exactly solvable mean-spherical and
      generalized mean-spherical models.
AB  - The hierarchical reference theory (HRT) and the self-consistent Ornstein-Zernike
      approximation (SCOZA) are two liquid state theories that both furnish a largely
      satisfactory description of the critical region as well as the phase coexistence
      and equation of state in general. Furthermore, there are a number of similarities
      that suggest the possibility of a unification of both theories. Earlier in this
      respect we have studied consistency between the internal energy and free energy
      routes. As a next step toward this goal we here consider consistency with the
      compressibility route too, but we restrict explicit evaluations to a model whose
      exact solution is known showing that a unification works in that case. The model
      in question is the mean spherical model (MSM) which we here extend to a
      generalized MSM. For this case, we show that the correct solutions can be
      recovered from suitable boundary conditions through either SCOZA or HRT alone as
      well as by the combined theory. Furthermore, the relation between the HRT-SCOZA
      equations and those of SCOZA and HRT becomes transparent.

PMID- 17500872
TI  - Cooperation enhanced by the difference between interaction and learning
      neighborhoods for evolutionary spatial prisoner's dilemma games.
AB  - We study an evolutionary prisoner's dilemma game with two layered graphs, where
      the lower layer is the physical infrastructure on which the interactions are
      taking place and the upper layer represents the connections for the strategy
      adoption (learning) mechanism. This system is investigated by means of Monte
      Carlo simulations and an extended pair-approximation method. We consider the
      average density of cooperators in the stationary state for a fixed interaction
      graph, while varying the number of edges in the learning graph. According to the
      Monte Carlo simulations, the cooperation is modified substantially in a way
      resembling a coherence-resonance-like behavior when the number of learning edges
      is increased. This behavior is reproduced by the analytical results.

PMID- 17500873
TI  - Density of states of a two-dimensional XY model from the Wang-Landau algorithm.
AB  - Using the Wang-Landau algorithm combined with the analytic method, the density of
      states of a two-dimensional XY model on square lattices of sizes 16x16, 24x24,
      and 32x32 is accurately calculated. Thermodynamic quantities, such as internal
      energy, free energy, entropy, and specific heat are obtained from the resulted
      density of states by numerical integration. It is found that both the density of
      states and the extensive thermodynamic quantities obey the scaling law. From the
      entropy curve, symptoms of phase transition are observed. A general method of
      calculation of the density of states of continuous models by simulation combined
      with analytical method is proposed.

PMID- 17500874
TI  - Time scale of random sequential adsorption.
AB  - A simple multiscale approach to the diffusion-driven adsorption from a solution
      to a solid surface is presented. The model combines two important features of the
      adsorption process: (i) The kinetics of the chemical reaction between adsorbing
      molecules and the surface and (ii) geometrical constraints on the surface made by
      molecules which are already adsorbed. The process (i) is modeled in a diffusion
      driven context, i.e., the conditional probability of adsorbing a molecule
      provided that the molecule hits the surface is related to the macroscopic surface
      reaction rate. The geometrical constraint (ii) is modeled using random sequential
      adsorption (RSA), which is the sequential addition of molecules at random
      positions on a surface; one attempt to attach a molecule is made per one RSA
      simulation time step. By coupling RSA with the diffusion of molecules in the
      solution above the surface the RSA simulation time step is related to the real
      physical time. The method is illustrated on a model of chemisorption of reactive
      polymers to a virus surface.

PMID- 17500875
TI  - Semiclassical master equation in Wigners phase space applied to Brownian motion
      in a periodic potential.
AB  - The quantum Brownian motion of a particle in a cosine periodic potential V(x)= 
      V{0}cos(x/x{0}) is treated using the master equation for the time evolution of
      the Wigner distribution function W(x,p,t) in phase space (x,p) . The dynamic
      structure factor, escape rate, and jump-length probabilities are evaluated via
      matrix continued fractions in the manner customarily used for the classical
      Fokker-Planck equation. The escape rate so yielded is compared with that given
      analytically by the quantum-mechanical reaction rate solution of the Kramers
      turnover problem. The matrix continued fraction solution substantially agrees
      with the analytic solution.

PMID- 17500876
TI  - Cluster size distribution in percolation theory and fractal Cantor dust.
AB  - Results of numerical simulation of cluster size distribution in the site
      percolation problem are presented. These results disagree with the theoretical
      data obtained on the basis of the standard drop model of finite cluster
      structure, in particular, they give a different value of exponent zeta (lnn{s}
      approximately -s{zeta}). Therefore, a more precise fractal model for describing
      the structure of clusters in a percolation system is proposed. The consideration
      is based on the solution of a kinetic equation for the number of finite clusters.
      In the framework of the proposed approach (fractal model together with kinetic
      equation), a correct value of exponent zeta is obtained and an explanation is
      given to the dependence of this exponent on the fraction of occupied sites p,
      which was revealed by numerical simulations. Additionally, a relation is
      established between the characteristics of cluster size distribution and fractal
      dimension of the Cantor dust constructed on the percolation cluster.

PMID- 17500877
TI  - Beyond Boltzmann-Gibbs statistics: maximum entropy hyperensembles out of
      equilibrium.
AB  - What is the best description that we can construct of a thermodynamic system that
      is not in equilibrium, given only one, or a few, extra parameters over and above
      those needed for a description of the same system at equilibrium? Here, we argue
      the most appropriate additional parameter is the nonequilibrium entropy of the
      system. Moreover, we should not attempt to estimate the probability distribution
      of the system directly, but rather the metaprobability (or hyperensemble) that
      the system is described by a particular probability distribution. The result is
      an entropic distribution with two parameters, one a nonequilibrium temperature,
      and the other a measure of distance from equilibrium. This dispersion parameter
      smoothly interpolates between certainty of a canonical distribution at
      equilibrium and great uncertainty as to the probability distribution as we move
      away from equilibrium. We deduce that, in general, large, rare fluctuations
      become far more common as we move away from equilibrium.

PMID- 17500878
TI  - Modeling percolation in high-aspect-ratio fiber systems. I. Soft-core versus hard
      core models.
AB  - Numerical and analytical studies of the onset of percolation in high-aspect-ratio
      fiber fiber systems such as nanotube reinforced polymers available in the
      literature have consistently modeled fibers as penetrable, straight, capped
      cylinders, also referred to as spherocylinders. In reality, however, fibers of
      very high-aspect ratio embedded in a polymer do not come into direct physical
      contact with each other, let alone exhibit any degree of penetrability. Further,
      embedded fibers of very high-aspect ratio are often actually wavy, rather than
      straight. In this two-part paper we address these critical differences between
      known physical systems, and the presently used spherocylinder percolation model.
      In Paper I we evaluate the effect of allowing penetration of the model fibers on
      simulation results by comparing the soft-core and the hard-core approaches to
      modeling percolation onset. We use Monte Carlo simulations to investigate the
      relationship between percolation threshold and excluded volume for both modeling
      approaches. Our results show that the generally accepted inverse proportionality
      between percolation threshold and excluded volume holds for both models. We
      further demonstrate that the error introduced by allowing the fibers to intersect
      is non-negligible, and is a function of both aspect ratio and tunneling distance.
      Thus while the results of both the soft-core model and hard-core assumptions can
      be matched to select experimental results, the hard-core model is more
      appropriate for modeling percolation in nanotubes-reinforced composites. The hard
      core model can also potentially be used as a tool in calculating the tunneling
      distance in composite materials, given the fiber morphology and experimentally
      derived electrical percolation threshold. In Paper II we investigate the effect
      of the waviness of the fibers on the onset of percolation in fiber reinforced
      composites.

PMID- 17500879
TI  - Modeling percolation in high-aspect-ratio fiber systems. II. The effect of
      waviness on the percolation onset.
AB  - The onset of electrical percolation in nanotube-reinforced composites is often
      modeled by considering the geometric percolation of a system of penetrable,
      straight, rigid, capped cylinders, or spherocylinders, despite the fact that
      embedded nanotubes are not straight and do not penetrate one another. In Part I
      of this work we investigated the applicability of the soft-core model to the
      present problem, and concluded that the hard-core approach is more appropriate
      for modeling electrical percolation onset in nanotube-reinforced composites and
      other high-aspect-ratio fiber systems. In Part II, we investigate the effect of
      fiber waviness on percolation onset. Previously, we studied extensively the
      effect of joint morphology and waviness in two-dimensional nanotube networks. In
      this work, we present the results of Monte Carlo simulations studying the effect
      of waviness on the percolation threshold of randomly oriented fibers in three
      dimensions. The excluded volumes of fibers were found numerically, and
      relationships between these and percolation thresholds for two different fiber
      morphologies were found. We build on the work of Part I, and extend the results
      of our soft-core, wavy fiber simulations to develop an analytical solution using
      the more relevant hard-core model. Our results show that for high- aspect-ratio
      fibers, the generally accepted inverse proportionality between percolation
      threshold and excluded volume holds, independent of fiber waviness. This suggests
      that, given an expression for excluded volume, an analytical solution can be
      derived to identify the percolation threshold of a system of high-aspect-ratio
      fibers, including nanotube-reinforced composites. Further, we show that for high
      aspect ratios, the percolation threshold of the wavy fiber networks is directly
      proportional to the analytical straight fiber solution and that the constant of
      proportionality is a function of the nanotube waviness only. Thus the onset of
      percolation can be adequately modeled by applying a factor based on fiber
      geometry to the analytical straight fiber solution.

PMID- 17500880
TI  - Characteristics of deterministic and stochastic sandpile models in a rotational
      sandpile model.
AB  - Rotational constraint representing a local external bias generally has a
      nontrivial effect on the critical behavior of lattice statistical models in
      equilibrium critical phenomena. In order to study the effect of rotational bias
      in an out-of-equilibrium situation like self-organized criticality, a two state
      "quasideterministic" rotational sandpile model is developed here imposing
      rotational constraint on the flow of sand grains. An extended set of critical
      exponents are estimated to characterize the avalanche properties at the
      nonequilibrium steady state of the model. The probability distribution functions
      are found to obey usual finite size scaling supported by negative time
      autocorrelation between the toppling waves. The model exhibits characteristics of
      both deterministic and stochastic sandpile models.

PMID- 17500881
TI  - Coarsening of "clouds" and dynamic scaling in a far-from-equilibrium model
      system.
AB  - A two-dimensional lattice gas of two species, driven in opposite directions by an
      external force, undergoes a jamming transition if the filling fraction is
      sufficiently high. Using Monte Carlo simulations, we investigate the growth of
      these jams (''clouds''), as the system approaches a nonequilibrium steady state
      from a disordered initial state. We monitor the dynamic structure factor
      S(k{x},k{y};t) and find that the k{x}=0 component exhibits dynamic scaling, of
      the form S(0,k{y};t)=t;{beta}S[over](k{y}t;{alpha}) . Over a significant range of
      times, we observe excellent data collapse with alpha=12 and beta=1 . The effects
      of varying filling fraction and driving force are discussed.

PMID- 17500882
TI  - Probability distribution of work done on a two-level system during a
      nonequilibrium isothermal process.
AB  - We present an exact calculation of the probability density for the work done by
      an external agent on a two-level system. Due to the external drive, both the
      transition rates between the two states and their energies depend on time. Within
      this setting we calculate the probability of every possible sample path of the
      system evolution and also the work done along any such path. The general
      procedure yields an evolution equation for the characteristic function of the
      work. Assuming that the energies change with constant rates, the properties of
      the work distribution are controlled by a single parameter representing the ratio
      of the time scales of the driving protocol, and of the internal dynamics,
      respectively. We calculate the mean work and characterize those sample paths
      which are not in agreement with the second law. In the slow driving limit, the
      probability density for the work collapses to a delta function localized at the
      reversible work. In the strongly nonequilibrium regime, the most probable work is
      smaller and the mean work is bigger than the reversible work.

PMID- 17500883
TI  - Thermal quantum electrodynamics of nonrelativistic charged fluids.
AB  - The theory relevant to the study of matter in equilibrium with the radiation
      field is thermal quantum electrodynamics (TQED). We present a formulation of the
      theory, suitable for nonrelativistic fluids, based on a joint functional integral
      representation of matter and field variables. In this formalism cluster expansion
      techniques of classical statistical mechanics become operative. They provide an
      alternative to the usual Feynman diagrammatics in many-body problems, which is
      not perturbative with respect to the coupling constant. As an application we show
      that the effective Coulomb interaction between quantum charges is partially
      screened by thermalized photons at large distances. More precisely one observes
      an exact cancellation of the dipolar electric part of the interaction, so that
      the asymptotic particle density correlation is now determined by relativistic
      effects. It still has the r(-6) decay typical for quantum charges, but with an
      amplitude strongly reduced by a relativistic factor.

PMID- 17500884
TI  - Theory of ground ice stability in sublimation environments.
AB  - Permanently stable ground ice is found beneath a permanently frost free surface
      on Mars, and similar conditions exist in the Antarctic Dry Valleys. This
      phenomenon is due to a balance of the vapor pressure of the ice with the
      atmospheric humidity in the presence of large amplitude temperature oscillations.
      An exactly solvable model example shows that the fraction of time the atmosphere
      needs to be saturated to stabilize the ice decreases with temperature amplitude.
      It is estimated that for conditions that prevail on Mars today, the mean
      temperature needs to be about 5K lower than the frost point temperature for
      ground ice to be stable. A decomposition method to evaluate the contribution of
      short term weather events to ground ice stability is developed; when applied to a
      study site in the Dry Valleys, it reveals that the coldest periods contribute
      most to stabilization.

PMID- 17500885
TI  - Temperature effects on phase equilibrium and diffusion in mesopores.
AB  - The equilibrium and dynamic properties of fluids confined to mesoporous material
      have been studied using nuclear magnetic resonance (NMR) methods. Molecular
      diffusion of n -pentane in Vycor porous glass within closed sample tubes has been
      measured by means of the pulsed field gradient (PFG) NMR method for temperatures
      notably exceeding the boiling point of the neat liquid. It is found that the
      temperature dependence of the diffusivity dramatically depends on the state of
      the fluid surrounding the mesoporous monoliths. In an oversaturated sample, i.e.,
      in a sample containing some amount of the liquid also outside of the porous
      material, the diffusivity in the mesopores followed the Arrhenius dependence. In
      samples with only the mesopores saturated by the liquid, i.e., without any excess
      fluid, with increasing temperature the diffusivity notably deviated from the
      Arrhenius dependence towards higher diffusivities. The analysis of the
      intensities of the respective NMR signals from the fluid within the porous
      material and in the surrounding phase has revealed that this anomaly is
      accompanied by the formation of a space free of liquid within the pore system.
      With the measured pore filling factors, the resulting overall diffusivity is
      estimated by a two-region approach with diffusion occurring in either the liquid
      phase or the free space within the pore volume. It is shown that this procedure,
      free of any fitting parameters, yields excellent agreement with the experimental
      data.

PMID- 17500886
TI  - Stochastic flow rule for granular materials.
AB  - There have been many attempts to derive continuum models for dense granular flow,
      but a general theory is still lacking. Here, we start with Mohr-Coulomb
      plasticity for quasi-two-dimensional granular materials to calculate (average)
      stresses and slip planes, but we propose a "stochastic flow rule" (SFR) to
      replace the principle of coaxiality in classical plasticity. The SFR takes into
      account two crucial features of granular materials-discreteness and randomness
      via diffusing "spots" of local fluidization, which act as carriers of plasticity.
      We postulate that spots perform random walks biased along slip lines with a drift
      direction determined by the stress imbalance upon a local switch from static to
      dynamic friction. In the continuum limit (based on a Fokker-Planck equation for
      the spot concentration), this simple model is able to predict a variety of
      granular flow profiles in flat-bottom silos, annular Couette cells, flowing
      heaps, and plate-dragging experiments--with essentially no fitting parameters-
      although it is only expected to function where material is at incipient failure
      and slip lines are inadmissible. For special cases of admissible slip lines, such
      as plate dragging under a heavy load or flow down an inclined plane, we postulate
      a transition to rate-dependent Bagnold rheology, where flow occurs by sliding
      shear planes. With different yield criteria, the SFR provides a general framework
      for multiscale modeling of plasticity in amorphous materials, cycling between
      continuum limit-state stress calculations, mesoscale spot random walks, and
      microscopic particle relaxation.

PMID- 17500887
TI  - Friction and relative energy dissipation in sheared granular materials.
AB  - The oscillating cylinder of a low-frequency inverted torsion pendulum is immersed
      into layers of noncohesive granular materials, including fine sand and glass
      beads. The relative energy dissipation and relative modulus of the granular
      system versus the amplitude and immersed depth of the oscillating cylinder are
      measured. A rheological model based on a mesoscopic picture is presented. The
      experimental results and rheological model indicate that small slides in the
      inhomogeneous force chains are responsible for the energy dissipation of the
      system, and the friction of the grains plays two different roles in the
      mechanical response of sheared granular material: damping the energy and
      enhancing the elasticity.

PMID- 17500888
TI  - Slow, nondiffusive dynamics in concentrated nanoemulsions.
AB  - Using multispeckle x-ray photon correlation spectroscopy, we have measured the
      slow, wave-vector-dependent dynamics of concentrated, disordered nanoemulsions
      composed of silicone oil droplets in water. The intermediate scattering function
      possesses a compressed exponential line shape and a relaxation time that varies
      inversely with wave vector. We interpret this dynamics as strain in response to
      local stress relaxation. The motion includes a transient component whose
      characteristic velocity decays exponentially with time following a mechanical
      perturbation of the nanoemulsions and a second component whose characteristic
      velocity is essentially independent of time. The steady-state characteristic
      velocity is surprisingly insensitive to the droplet volume fraction in the
      concentrated regime, indicating that the strain motion is only weakly dependent
      on the droplet-droplet interactions.

PMID- 17500889
TI  - Fluctuations in chemical gelation.
AB  - We study a chemical gelation model in two dimensions which includes both monomer
      aggregations and bond fluctuations. Our numerical simulation shows that a sol-gel
      transition occurs when an initial monomer concentration is above a critical
      concentration. Fractal aggregates grow until the sol-gel transition occurs. After
      the gelation, however, bond fluctuations break the fractal structure and an
      interesting inhomogeneous gel fiber network appears instead. A pore size
      distribution of the inhomogeneous structure shows the existence of hierarchical
      structures in the gel phase. It is also found that slow dynamics appear near the
      critical concentration.

PMID- 17500890
TI  - Hindered mobility of a particle near a soft interface.
AB  - The translational motion of a solid sphere near a deformable fluid interface is
      studied in the low Reynolds number regime. In this problem, the fluid flow driven
      by the sphere is dynamically coupled to the instantaneous conformation of the
      interface. Using a two-dimensional Fourier transform technique, we are able to
      account for the multiple backflows scattered from the interface. The correction
      to the mobility tensor is then obtained from the matrix elements of the relevant
      Green's function. Our perturbative analysis allows us to express the explicit
      position and frequency dependence of the mobility for small particles. We recover
      in the steady limit the result for a sphere near a perfectly flat interface. At
      intermediate time scales, the mobility exhibits an imaginary part which is a
      signature of the elastic response of the interface. In the short time limit, we
      find that the perpendicular mobility may, under some circumstances, become lower
      than the bulk value. All the results can be explained using the definition of the
      relaxation time of the soft interface.

PMID- 17500892
TI  - Sedimentation of charged colloids: the primitive model and the effective one
      component approach.
AB  - Sedimentation-diffusion equilibrium density profiles of suspensions of charge
      stabilized colloids are calculated theoretically and by Monte Carlo (MC)
      simulations, both for a one-component model of colloidal particles interacting
      through pairwise screened-Coulomb repulsions and for a three-component model of
      colloids, cations, and anions with unscreened-Coulomb interactions. We focus on a
      state point for which experimental measurements are available [C. P. Royall, J.
      Phys.: Condens Matter 17, 2315 (2005)]. Despite the apparently different picture
      that emerges from the one- and three-component models (repelling colloids pushing
      each other to high altitude in the former, versus a self-generated electric field
      that pushes the colloids up in the latter), we find similar colloidal density
      profiles for both models from theory as well as simulation, thereby suggesting
      that these pictures represent different viewpoints of the same phenomenon. The
      sedimentation profiles obtained from an effective one-component model by MC
      simulations and theory, together with MC simulations of the multicomponent
      primitive model are consistent among themselves, but differ quantitatively from
      the results of a theoretical multicomponent description at the Poisson-Boltzmann
      level. We find that for small and moderate colloid charge the Poisson-Boltzmann
      theory gives profiles in excellent agreement with the effective one-component
      theory if a smaller effective charge is used. We attribute this discrepancy to
      the poor treatment of correlations in the Poisson-Boltzmann theory.

PMID- 17500891
TI  - Rupture and healing of one-dimensional chains in a parametric magnetic ratchet
      potential.
AB  - Transverse paramagnetic particle chains parametrically driven by a magnetic
      ratchet potential rupture and heal upon collision with an obstacle. The
      overdamped transverse dynamics is frozen during the time the particles stay in
      the ratchet potential wells and kicked during the time the particles hop to the
      next well. On time scales large compared to the parametric modulation period the
      healing of the hole in the chain is determined by dipolar repulsion and
      hydrodynamic friction of the paramagnetic particles.

PMID- 17500893
TI  - Effective potential between two spheres in a suspension of adhesive rods.
AB  - Analytic treatment and Monte Carlo simulations are used to study the effective
      potential between two spheres in a suspension of rods whose ends can adhere to
      the surface of the spheres. When only one end of each rod is adhesive the
      effective potential changes from being attractive to repulsive with enhancing the
      adherence, but when both ends of each rod are adhesive the effective potential is
      not a monotonic function of the distance between the two spheres for strong
      adherence. As the adhesive strength is fixed, the range of the effective
      potential will increase with increasing the length of the rods. When the adhesive
      range is much smaller than the diameter of the spheres, its influence on single
      end adhesion is approximately linear and on two end adhesion is about quadratic.
      Our results are qualitatively consistent with a recent experimental work.

PMID- 17500894
TI  - Irreversible shear-induced vitrification of droplets into elastic nanoemulsions
      by extreme rupturing.
AB  - Many materials weaken through fracturing when subjected to extreme stresses. By
      contrast, we show that breaking down repulsive bits of matter dispersed in a
      viscous liquid can cause a dramatic and irreversible increase in the dispersion's
      elasticity. Anionically stabilized microscale emulsions subjected to a history of
      high-pressure microfluidic flow can develop an unusually large elastic modulus as
      droplets are ruptured to the nanoscale, yielding "nanonaise." As the droplet size
      approaches the Debye screening length, the nanoemulsion vitrifies. Consequently,
      the onset of elasticity for disordered uniform nanoemulsions can occur at droplet
      volume fractions far below maximal random jamming of spheres.

PMID- 17500895
TI  - Two-dimensional colloidal aggregation mediated by the range of repulsive
      interactions.
AB  - We study the effect of the interaction's range on the structural and kinetic
      properties of a computer-simulated two-dimensional aggregating colloidal system.
      For this purpose, we considered that the particles of the system interact through
      a repulsive Yukawa potential which depends on two parameters: the value of the
      interaction potential between particles in contact V0 and the range of the
      interaction kappa(d) . We observed that the increase of the interaction range or
      V0 provokes the arrangement of the small aggregates in linear structures. The
      repulsive interactions have also a strong influence on the kinetic behavior of
      the coagulation process. Indeed, they induce the formation of three different
      time-separated aggregation regimes. In the first regime (at early states) the
      aggregation is dominated by the range of the repulsive forces, and the cluster
      cluster repulsion increases with the cluster size. The second regime (at
      intermediate times) is reached when the average cluster size is larger than the
      interaction range. Here, the cluster-cluster repulsions do not grow anymore with
      the cluster size, so the probability of overcoming the repulsive barrier is the
      same for all clusters. This corresponds with the so-called reaction-limited
      cluster-aggregation regime, where more than one collision between the clusters is
      needed to form a bond. The third aggregation regime is found at long aggregation
      times. In this region the coagulation is mainly determined by the diffusion time
      and the kinetics becomes diffusion controlled. A physical interpretation for the
      transition between chain structures and the typical fractals aggregates from the
      point of view of the range of the interactions is discussed. Moreover, a method
      has been developed in order to obtain the effect of the interactions with a non
      negligible range over the aggregation rates directly from the simulations. The
      relation between these different regions with the parameters of the interaction
      potential V0 and kappa(d) is analyzed.

PMID- 17500896
TI  - Metabasin dynamics and local structure in supercooled water.
AB  - We employ the distance matrix method to investigate metabasin dynamics in
      supercooled water. We find that the motion of the system consists in the
      exploration of a finite region of configuration space (enclosing several distinct
      local minima), named metabasin, followed by a sharp crossing to a different
      metabasin. The characteristic time between metabasin transitions is comparable to
      the structural relaxation time, suggesting that these transitions are relevant
      for the long-time dynamics. The crossing between metabasins is accompanied by
      very rapid diffusional jumps of several groups of dynamically correlated
      particles. These particles form relatively compact clusters and act as
      cooperative relaxing units responsible for the density relaxation. We find that
      these mobile particles are often characterized by an average coordination larger
      than four, i.e., they are located in regions where the tetrahedral hydrogen bond
      network is distorted.

PMID- 17500897
TI  - Conventional methods fail to measure cp (omega) of glass-forming liquids.
AB  - The specific heat is frequency dependent in highly viscous liquids. By solving
      the full one-dimensional thermoviscoelastic problem analytically it is shown
      that, because of thermal expansion and the fact that mechanical stresses relax on
      the same time scale as the enthalpy relaxes, the plane thermal-wave method does
      not measure the isobaric frequency-dependent specific heat c{p}(omega) . This
      method rather measures a "longitudinal" frequency-dependent specific heat, a
      quantity defined and detailed here that is in between c{p}(omega) and c{V}(omega)
      . This result means that no reliable wide-frequency measurements of c{p}(omega)
      on liquids approaching the calorimetric glass transition exist. We briefly
      discuss consequences for experiment.

PMID- 17500898
TI  - Heterogeneous dynamics in polycrystal and glass in a binary mixture with changing
      size dispersity and composition.
AB  - Using molecular dynamics simulation we investigate the dynamics in a two
      dimensional binary mixture at a low temperature and at high densities. We
      increase the size ratio of the diameters of the two components or the fraction of
      the larger particles. Then changeovers occur from polycrystal to glass with
      proliferation of defects. The relationship between the degree of disorder and the
      slow dynamics is studied by simultaneous visualization of a disorder variable
      D{j} introduced in our previous paper T. Hamanaka and A. Onuki[Phys. Rev. E 74,
      011506 (2006)] and the particle displacement Deltar{j} in a long time interval.
      In polycrystal, the particles in the grain boundary regions have large D{j} and a
      relatively large mobility, producing significant dynamic heterogeneity on long
      time scales. In the crossover from polycrystal to glass, the crystalline regions
      become narrow, but the particles with relatively large D{j} still trigger the
      formation of chainlike particle motions, leading to the dynamic heterogeneity.

PMID- 17500899
TI  - Structural transitions and arrest of domain growth in sheared binary immiscible
      fluids and microemulsions.
AB  - We investigate spinodal decomposition and structuring effects in binary
      immiscible and ternary amphiphilic fluid mixtures under shear by means of three
      dimensional lattice Boltzmann simulations. We show that the growth of individual
      fluid domains can be arrested by adding surfactant to the system, thus forming a
      bicontinuous microemulsion. We demonstrate that the maximum domain size and the
      time of arrest depend linearly on the concentration of amphiphile molecules. In
      addition, we find that for a well-defined threshold value of amphiphile
      concentration, the maximum domain size and time of complete arrest do not change.
      For systems under constant and oscillatory shear we analyze domain growth rates
      in directions parallel and perpendicular to the applied shear. We find a
      structural transition from a sponge to a lamellar phase by applying a constant
      shear and the occurrence of tubular structures under oscillatory shear. The size
      of the resulting lamellae and tubes depends strongly on the amphiphile
      concentration, shear rate, and shear frequency.

PMID- 17500900
TI  - Microrheology of viscoelastic fluids containing light-scattering inclusions.
AB  - The microrheology of viscoelastic fluids containing light-scattering inclusions
      is measured by depolarized dynamic light scattering (DDLS) from optically
      anisotropic spherical colloidal probes. The anisotropy of the probes allows us to
      measure both their translational and the rotational mean squared displacements
      simultaneously, and DDLS allows us to suppress the light scattered from the
      inclusions. The storage and loss moduli are determined from both mean squared
      displacements and the results compared with mechanical measurements.

PMID- 17500901
TI  - Acoustical observation of bubble oscillations induced by bubble popping.
AB  - Acoustic measurements of aqueous foams show three distinct radiation mechanisms
      that contribute to the sound pressure field: oscillations of a bubble surface
      that precede popping due to the instability of thin liquid film, impulsive
      radiation due to bursts of bubbles, and oscillations from neighboring bubbles
      excited by a burst bubble. The movies captured by a fast camera confirm that the
      bubbles adjacent to a breaking bubble oscillate under the influence of the
      pressure generated by the burst bubble. The spectra of resulting transient sounds
      fall in the range of 2-8 kHz and those from bubble oscillations correlate well
      with the bubble size.

PMID- 17500902
TI  - Effect of elastic interactions on coarsening in elastically inhomogeneous
      multiphase systems.
AB  - We investigate the effect of interactions between inclusions on the coarsening
      behavior of elastically inhomogeneous multiphase systems with lattice misfit
      using a recently introduced two-dimensional multiscale model based on the
      classical time-dependent density-functional theory. We show that spontaneous
      shape changes are very efficient in limiting the impact of the interactions on
      the chemical potential of inclusions. For this reason, the interactions between
      isolated pairs of inclusions are unable to significantly affect coarsening. At
      higher volume fraction, the efficiency of shape changes drops and major shifts of
      the chemical potential are observed; these are shown to be strong enough to
      counteract capillarity. For example, we show that sufficient confinement by
      neighboring inclusions causes inverse coarsening and we provide illustrations of
      this. We also examine the effect of interface elasticity in the presence of
      interactions. We demonstrate that elasticity induces kinetic faceting and gives
      rise to oscillations in the chemical potential of the inclusions. This is shown
      to lead to the stabilization of microstructures composed of inclusions of various
      sizes. Finally, we propose a simple modified Lifshitz-Slyozov-Wagner model for
      assessing the effect of interactions on coarsening. The results are shown to be
      in excellent agreement with experiment.

PMID- 17500903
TI  - Laser-induced structure formation on stretched polymer foils.
AB  - Noncoherent structures that develop during UV laser ablation of stretched
      semicrystalline polymer foils are a very general phenomenon. A thermodynamic
      model based on stress relaxation within the modified layer of the polymer surface
      describes the main features of the observed phenomena, and, in particular, the
      dependence of the period of structures on laser wavelength, fluence, and number
      of laser pulses.

PMID- 17500904
TI  - Influence of strain on the kinetics of phase transitions in solids.
AB  - We consider a sharp interface kinetic model of phase transitions accompanied by
      elastic strain, together with its phase-field realization. Quantitative results
      for the steady-state growth of a new phase in a strip geometry are obtained, and
      different pattern formation processes in this system are investigated.

PMID- 17500905
TI  - Continuum theory of a moving membrane.
AB  - We derive a set of equations for the dynamics of evolving fluid membranes, such
      as cell membranes, in the presence of bulk fluids. We model the membrane as a
      surface endowed with a director field, which describes the local average
      orientation of the molecules on the membrane. A model for the elastic energy of a
      surface endowed with a director field is derived using liquid crystal theory.
      This elastic energy reduces to the well-known Helfrich energy in the limit when
      the directors are constrained to be normal to the surface. We then derive the
      full dynamic equations for the membrane that incorporate both the elastic and
      viscous effects, with and without the presence of bulk fluids. We also consider
      the effect of local spontaneous curvature, arising from the presence of membrane
      proteins. Overall, the systems of equations allow us to carry out stable,
      accurate, and robust numerical modeling for the dynamics of the membranes.

PMID- 17500906
TI  - Dripping of a crystal.
AB  - Dripping is usually associated with fluid motion, but here we describe the
      analogous phenomenon of a 3He crystal growing and melting under the influence of
      surface tension and gravity. The pinch-off of the crystal is described by a
      purely geometric equation of motion, viscous dissipation or inertia being
      negligible. In analogy to fluid pinch-off, the minimum neck radius R{n} goes to
      zero like a power law, but with a new scaling exponent of 12 . However, for a
      significant part of the neck's macroscopic evolution the scaling exponent is
      found to be much closer to 13 . This observation may be consistent with
      simulations and theoretical results showing a very slow approach to the
      asymptotic pinch solution, making the "critical region" very small, both in time
      and space. After pinch-off, we observe a similar 13 -scaling for the recoil of a
      crystal tip, both in simulation and experiment. For very early times our
      experiments are consistent with an approximate theory predicting an asymptotic
      regime with exponent 12 . Future experiments must show whether the transient 13
      scaling is a universal feature of crystal melting, or perhaps an artifact of our
      experimental setup.

PMID- 17500907
TI  - Structure-flexoelastic properties of bimesogenic liquid crystals.
AB  - In this paper, we report on the flexoelastic and viscoelastic ratios for a number
      of bimesogens compounds with the same generic structure. Values are obtained
      indirectly by measuring the flexoelectro-optic response in the chiral nematic
      phase. By varying the molecular structure we alter the bend angle, transverse
      dipole moment, and length of the molecule. First, to examine the influence of the
      bend angle we use a homologous series whereby the only alteration in the
      molecular structure is the number of methylene units in the aliphatic spacer, n .
      Results show that the flexoelastic ratio, e/K , and the effective flexoelectric
      coefficient, e , both exhibit an odd-even effect with values for n=odd being
      greater than that for n=even . This is understood in terms of an increase in the
      bend angle of the molecule and an increase in the transverse dipole moment.
      Second, in order to investigate the impact of the dipole moment, we have altered
      the mesogenic units so as to vary the longitudinal dipole moment and used
      different linkages in the aliphatic spacer in an attempt to alter the transverse
      dipole moment. Qualitatively, the results demonstrate that the odd-spaced
      bimesogen with larger transverse dipole moments exhibit larger flexoelastic
      ratios.

PMID- 17500908
TI  - Surface deformation of nematic elastomers under striped illumination.
AB  - Nematic elastomers containing azobenzene chromophores are activated upon
      photoabsorption. We study the surface deformation of such elastomers under
      striped illumination. For an arbitrary orientation of the nematic axis, we obtain
      an analytical solution to the problem via a phenomenological continuum model.
      Numerical computations indicate that the profile of the deformed surface depends
      not only on the stripe width but also on the orientation of the nematic axis. The
      result may provide a mechanism to manipulate the surface topography of
      elastomers.

PMID- 17500909
TI  - Computer simulations of wetting of solid surfaces by liquid crystals.
AB  - Atomistic computer simulations are presented, consisting of droplets of model
      liquid crystal molecules wetting a generic crystalline surface. It is shown that
      the type of wetting that occurs is highly dependent on the value of the surface
      interaction parameter epsilon{fs} , switching between partial wetting (no
      spreading) for epsilon{fs}=2.0 to complete wetting for epsilon{fs}=2.5 .
      epsilon{fs} is the multiplicative factor which scales the well depth of the fluid
      surface interaction energy. During complete wetting, the spreading occurs through
      the growth of a precursor layer, and a set of secondary terraces. The temperature
      affects the structure of the droplet, as might be expected when different phases
      are sampled, and also the shape of the spreading droplet, and the rate of
      spreading. In particular, in the smectic-A phase at 350K, for values of
      epsilon{fs} just large enough to induce complete wetting, the precursor film
      assumes a diamond shape, with edges normal to the [110] directions in the crystal
      surface. It is shown that spreading occurs through diffusion across the surface,
      with the radius of the precursor layer increasing with the square root of time.
      Mass flow studies indicate that the spreading occurs by molecules cascading over
      the top of the droplet to feed the growing precursor layer. Calculations of
      contact angle relaxation are in qualitative agreement with experimental findings.

PMID- 17500910
TI  - Theoretical analysis of the magnetic Freedericksz transition in the presence of
      flexoelectricity and ionic contamination.
AB  - We have derived an approximate analytical expression for the static director
      distortion of a planar nematic layer subject to a magnetic field H immediately
      above the critical Freedericksz transition H=H{c} . The layer contains a voltage
      independent density of positively and negatively singly charged ionic species
      that interact with the flexoelectric and dielectric polarizations which appear
      when the director is distorted. The analytical solution is shown to correspond
      closely to a full numerical calculation when H/H{c}=1.01. The analytical approach
      allows a quantitative insight into how the mobile charge shields the polarization
      for different values of the elastic constants, the ionic density, the
      flexoelectric coefficients, and the layer thickness.

PMID- 17500911
TI  - Uniaxial rebound at the nematic biaxial transition.
AB  - Over the last few years, renewed interest has been raised by the simplified
      general interaction models proposed by Straley for mesogenic molecules possessing
      the D{2h} symmetry and capable of producing biaxial nematic order. It has already
      been shown that, in the presence of certain special symmetries, just two out of
      the four order parameters that are in general necessary, suffice for the
      description of a biaxial phase. For some other range of parameters, these
      reducing symmetries do not hold, and, moreover, a mean-field treatment has to be
      suitably changed into a minimax strategy, still producing a transition to a low
      temperature biaxial phase. Upon studying the general parameter range, we identify
      as a common feature the behavior of a uniaxial order parameter, attaining a local
      minimum at the biaxial-to-uniaxial transition temperature, and recognizably
      increasing away from it. This finding is confirmed by a Monte Carlo simulation.

PMID- 17500912
TI  - Shape evolution of a single liquid-crystal droplet immersed in an isotropic
      matrix under transient and steady flow.
AB  - The morphology evolution of immiscible polymer-liquid crystal systems is quite
      different from flexible polymer-polymer mixtures due to the anisotropic
      properties of liquid crystals. The deformation and retraction of a single low
      molar mass liquid crystal 4'-pentyl-4-biphenylcarbonitrile (5CB) droplet and 4'
      octyl-4-biphenylcarbonitrile (8CB) dispersed in polydimethyl-siloxane under two
      dimensional linear flow was investigated by a computer-controlled four-roll mill,
      which is equipped with an optical microscope and a digital camera. The
      deformation parameter and orientation angle during deformation versus capillary
      number was obtained and compared with calculations using the Maffettone-Minale
      (MM) model and the Yu-Zhou liquid-crystal (YZ-LC) model. The MM model can
      describe the behavior of a Newtonian droplet in another Newtonian matrix whereas
      the YZ-LC model can describe the behavior of a LC droplet in a Newtonian matrix.
      The results showed that the deformation and rotation of a LC droplet is more
      difficult than viscoelastic droplets, possibly because of the resistance of the
      nematic elastic energy induced by the nematic mesogens deformation and
      orientation under flow field. Furthermore, the different behavior between flow
      aligning 5CB and flow-tumbling 8CB droplets and the influence of droplet size of
      LC on deformation and retraction were discussed by experiment and calculation;
      the results reveal that the different size LC droplets show different evolution
      curves.

PMID- 17500913
TI  - Structural properties of crystallizable polymer melts: Intrachain and interchain
      correlation functions.
AB  - We present results from constant pressure molecular-dynamics simulations for a
      bead-spring model of a crystallizable polymer melt. Our model has two main
      features, a chemically realistic intrachain rigidity and a purely repulsive
      interaction between nonbonded monomers. By means of intrachain and interchain
      structure factors we explore polymer conformation and melt structure above and
      below the temperature T{crys}{hom} of homogeneous crystallization. Here, we do
      not only determine average spatial correlations, but also site-specific
      correlations which depend on the position of the monomers along the polymer
      backbone. In the liquid phase above T{crys}{hom} we find that this site
      dependence can be well-accounted for by known theoretical approximations, the
      Koyama distribution for the intrachain structure and the polymer reference
      interaction site model (PRISM) for the interchain structure. This is no longer
      true in the semicrystalline phase. Below T{crys}{hom} short chains fully extend
      upon crystallization, whereas sufficiently long chains form chain-folded lamellae
      which coexist with amorphous regions. The structural features of these polymer
      crystals lead to violations of premises of the Koyama approximation or PRISM
      theory so that both theoretical approaches cannot be applied simultaneously.
      Furthermore, we find a violation of the Hansen-Verlet freezing criterion; our
      polymer melt crystallizes more easily than a simple liquid. This hints at the
      importance of the coupling between conformation (backbone rigidity) and density
      (packing constraints) for polymer crystallization.

PMID- 17500914
TI  - Shear deformation of polymer melt observed via proton NMR: theory and experiment.
AB  - We here develop a theory for the effect of shearing flow on residual proton
      dipole-dipole interactions for polymer melts. The model is based on the use of
      correlation functions which derive from the return to origin probability for
      polymers reptating in the tube of surrounding constraints. Using Doi-Edwards
      theory we calculate the spin-echo response under equilibrium conditions and then
      consider the effect of a shearing flow which deforms the tube, finding that there
      exists a strong dependence of transverse relaxation on Weissenberg number. The
      results are compared with NMR measurements of shear-perturbed proton T2
      relaxation in 494kDa poly (dimethylsiloxane).

PMID- 17500915
TI  - Theoretically predicted effects of Gaussian curvature on lateral diffusion of
      membrane molecules.
AB  - Lateral diffusion on curved biological membranes has been studied theoretically
      and experimentally. However, how membrane geometries influence the diffusion
      process remains unclear. Here we show the significance of Gaussian curvature by
      numerically solving the diffusion equation in a geodesic polar coordinate system
      with regard to several types of surfaces including elliptic and hyperbolic
      paraboloids. On surfaces where Gaussian curvature has positive and negative
      values, diffusion is slower and faster than on the plane, respectively. The
      deviation from the normal diffusion on the plane tends to get larger as the
      absolute value of Gaussian curvature increases. Diffusion is anisotropic at a
      surface region where the normal curvature is anisotropic and Gaussian curvature
      has nonzero values. The anisotropy can be classified into several types according
      to whether diffusion is the fastest or the slowest in the principal directions.
      In the case of diffusion on spheroids, the limited area of a closed surface
      reduces the diffusion rate so greatly that the slowdown effects of positive
      values of Gaussian curvature are concealed. Analysis of the diffusion equation
      suggests that Gaussian curvature causes slowed or accelerated diffusion and
      anisotropic diffusion in any type of surface. Furthermore, it is discussed the
      degree to which Gaussian curvature influences diffusive phenomena taking place in
      real membranes through such effects. These results provide a different image of
      biological membranes that lateral diffusion of membrane molecules is usually
      anisotropic and the diffusion rate kaleidoscopically changes according to place.

PMID- 17500916
TI  - Sensitivity versus resonance in two-dimensional spiking-bursting neuron models.
AB  - Through phase plane analysis of a class of two-dimensional spiking and bursting
      neuron models, covering some of the most popular map-based neuron models, we show
      that there exists a trade-off between the sensitivity of the neuron to steady
      external stimulation and its resonance properties, and how this trade-off may be
      tuned by the neutral or asymptotic character of the slow variable. Implications
      of the results for the suprathreshold behavior of the neurons, both by themselves
      and as part of networks, are presented in different regimes of interest, such as
      the excitable, regular spiking, and bursting regimes. These results establish a
      consistent link between single-neuron parameters and resulting network dynamics,
      and will hopefully be useful as a guide for modeling.

PMID- 17500917
TI  - Laser intensity dependence of femtosecond near-infrared optoinjection.
AB  - We report an experimental study on transient membrane permeabilization of single
      living bovine aortic endothelial cells (BAEC) by tightly focused femtosecond near
      infrared laser pulses. The membrane permeabilization of the BAEC cells was
      studied as a function of the incident laser intensity. The rate of dye uptake by
      the cells was analyzed using time-lapse imaging. We found that membrane
      permeabilization occurs for laser intensities higher than 4.0 x 10(12) W/cm(2).
      For laser intensity above 3.3 x 10(13) W/cm(2) the cell disintegrates. Within
      these two limits the rate of dye uptake increases logarithmically with increasing
      laser intensity. This functional dependence is explained by considering the
      Gaussian intensity distribution across the laser focal spot. Cell membrane
      permeabilization is explained by the creation of a plasma within the laser focal
      spot. The physical understanding of the relationship between dye uptake, pore
      characteristics, and laser intensity allows control of the concentrations of
      molecules delivered into cells through the control of pore characteristics.

PMID- 17500918
TI  - Stretching short biopolymers by fields and forces.
AB  - We study the mechanical properties of semiflexible polymers when the contour
      length of the polymer is comparable to its persistence length. We compute the
      exact average end-to-end distance and shape of the polymer for different boundary
      conditions, and show that boundary effects can lead to significant deviations
      from the well-known long-polymer results. We also consider the case of stretching
      a uniformly charged biopolymer by an electric field, for which we compute the
      average extension and the average shape, which is shown to be trumpetlike. Our
      results also apply to long biopolymers when thermal fluctuations have been
      smoothed out by a large applied field or force.

PMID- 17500919
TI  - Intracellular transport by single-headed kinesin KIF1A: effects of single-motor
      mechanochemistry and steric interactions.
AB  - In eukaryotic cells, many motor proteins can move simultaneously on a single
      microtubule track. This leads to interesting collective phenomena such as
      jamming. Recently we reported [Phys. Rev. Lett. 95, 118101 (2005)] a lattice-gas
      model which describes traffic of unconventional (single-headed) kinesins KIF1A.
      Here we generalize this model, introducing an interaction parameter c, to account
      for an interesting mechanochemical process. We have been able to extract all the
      parameters of the model, except c, from experimentally measured quantities. In
      contrast to earlier models of intracellular molecular motor traffic, our model
      assigns distinct "chemical" (or, conformational) states to each kinesin to
      account for the hydrolysis of adenosine triphosphate (ATP), the chemical fuel of
      the motor. Our model makes experimentally testable theoretical predictions. We
      determine the phase diagram of the model in planes spanned by experimentally
      controllable parameters, namely, the concentrations of kinesins and ATP.
      Furthermore, the phase-separated regime is studied in some detail using
      analytical methods and simulations to determine, e.g., the position of shocks.
      Comparison of our theoretical predictions with experimental results is expected
      to elucidate the nature of the mechanochemical process captured by the parameter
      c.

PMID- 17500920
TI  - Magnetic control of Dictyostelium aggregation.
AB  - We report the control of cell migration by external magnetic forces during the
      early stage of Dictysostelium discoideum morphogenesis. Magnetically labeled
      aggregating cells respond to the presence of a magnetic field created by a thin
      magnetic tip: forces as low as 30 pN are sufficient to elicit the aggregation of
      the cells at the extremity of the tip. This induced magnetotaxis is competitive
      to classical chemotaxis. We therefore underline the interplay between external
      mechanical forces and morphogenesis. This magnetic assay will open new
      possibilities in the study of morphogenesis in Dictyostelium.

PMID- 17500921
TI  - Period-two cycles in a feedforward layered neural network model with symmetric
      sequence processing.
AB  - The effects of dominant sequential interactions are investigated in an exactly
      solvable feedforward layered neural network model of binary units and patterns
      near saturation in which the interaction consists of a Hebbian part and a
      symmetric sequential term. Phase diagrams of stationary states are obtained and a
      phase of cyclic correlated states of period two is found for a weak Hebbian term,
      independently of the number of condensed patterns c.

PMID- 17500922
TI  - Eukaryotic promoter prediction based on relative entropy and positional
      information.
AB  - The eukaryotic promoter prediction is one of the most important problems in DNA
      sequence analysis, but also a very difficult one. Although a number of algorithms
      have been proposed, their performances are still limited by low sensitivities and
      high false positives. We present a method for improving the performance of
      promoter regions prediction. We focus on the selection of most effective features
      for different functional regions in DNA sequences. Our feature selection
      algorithm is based on relative entropy or Kullback-Leibler divergence, and a
      system combined with position-specific information for promoter regions
      prediction is developed. The results of testing on large genomic sequences and
      comparisons with the PromoterInspector and Dragon Promoter Finder show that our
      algorithm is efficient with higher sensitivity and specificity in predicting
      promoter regions.

PMID- 17500923
TI  - Unfolding cross-linkers as rheology regulators in F-actin networks.
AB  - We report on the nonlinear mechanical properties of a statistically homogeneous,
      isotropic semiflexible network cross-linked by polymers containing numerous small
      unfolding domains, such as the ubiquitous F-actin cross-linker filamin. We show
      that the inclusion of such proteins has a dramatic effect on the large strain
      behavior of the network. Beyond a strain threshold, which depends on network
      density, the unfolding of protein domains leads to bulk shear softening. Past
      this critical strain, the network spontaneously organizes itself so that an
      appreciable fraction of the filamin cross-linkers are at the threshold of domain
      unfolding. We discuss via a simple mean-field model the cause of this network
      organization and suggest that it may be the source of power-law relaxation
      observed in in vitro and in intracellular microrheology experiments. We present
      data which fully justify our model for a simplified network architecture.

PMID- 17500924
TI  - Structural-diversity-enhanced cellular ability to detect subthreshold
      extracellular signals.
AB  - We study the influence of the structural diversity of cells on subthreshold
      agonist signals in coupled hepatocytes systems. The variance of the cellular
      structural parameter sigma is employed to characterize the structural diversity.
      It is found that structural diversity enhances the cellular ability to detect
      extracellular weak signals through intracellular Ca2+ oscillations and the
      regularity of Ca2+ spikes undergoes a maximum with a variation of sigma,
      indicating the occurrence of structural-diversity-induced coherence resonance.
      Furthermore, the effects of the level of subthreshold stimulus and junctional
      coupling strength on the behavior of Ca2+ dynamics are also considered. Analysis
      indicates that these phenomena have inherent relevance to both the bifurcation
      feature of a single cell and intercellular interaction through junctional
      coupling. Our findings may exhibit that structural diversity plays a constructive
      role in biological systems.

PMID- 17500925
TI  - Patterns in inhibitory networks of simple map neurons.
AB  - We study the dynamics of networks of inhibitory map-based bursting neurons.
      Linear analysis allows us to understand how the patterns of bursting are
      determined by network topology and how they depend on the strength of synaptic
      connections, when inhibition is balanced. Two kinds of patterns are found
      depending on the symmetry of the network: slow cyclic patterns riding on
      subthreshold oscillations where almost all neurons contribute bursts in a sparse
      manner and fast patterns of bursts in which only one of two mutually exclusive
      groups of neurons take part. We also discuss the properties of the neuron model
      that underlie the described phenomena, comment on the limitations of the
      technique of analysis, and point to some possible ways to overcome them.

PMID- 17500926
TI  - Non-Gaussian behavior of elastic incoherent neutron scattering profiles of
      proteins studied by molecular dynamics simulation.
AB  - Elastic incoherent neutron scattering (EINS) data can be approximated with a
      Gaussian function of q in a low q region. However, in a higher q region the
      deviation from a Gaussian function becomes non-negligible. Protein dynamic
      properties can be derived from the analyses of the non-Gaussian behavior, which
      has been experimentally investigated. To evaluate the origins of the non-Gaussian
      behavior of protein dynamics, we conducted a molecular dynamics (MD) simulation
      of staphylococcal nuclease. Instead of the ordinary cumulant expansion, we
      decomposed the non-Gaussian terms into three components: (i) the component
      originating from the heterogeneity of the mean-square fluctuation, (ii) that from
      the anisotropy, and (iii) that from higher-order terms such as anharmonicity. The
      MD simulation revealed various dynamics for each atom. The atomic motions are
      classified into three types: (i) "harmonic," (ii) "anisotropic," and (iii)
      "anharmonic." However, each atom has a different degree of anisotropy. The
      contribution of the anisotropy to the total scattering function averages out due
      to these differences. Anharmonic motion is described as the jump among multiple
      minima. The jump distance and the probability of the residence at one site vary
      from atom to atom. Each anharmonic component oscillates between positive and
      negative values. Thus, the contribution of the anharmonicity to the total
      scattering is canceled due to the variations in the anharmonicity. Consequently,
      the non-Gaussian behavior of the total EINS from a protein can be analyzed by the
      dynamical heterogeneity.

PMID- 17500927
TI  - Random fluctuations of the firing rate function in a continuum neural field
      model.
AB  - We incorporate a source of noise into a continuum neural field model by allowing
      the firing threshold to fluctuate noisily about a mean value, and examine
      traveling wave front solutions. Under certain conditions we are able to calculate
      the first and second moments of the distributions of the resulting time varying
      front speed and shape. This is then compared with more complete numerical
      solutions. Fluctuations in the wave front speed and in the shape (i.e.,
      fluctuations in activity at particular coordinate positions across the wave
      front) were found to increase as the magnitude of the fluctuations in firing
      threshold increased. The mean speed was found to increase as the magnitude of the
      fluctuations increases. The role of the correlation time for the threshold
      variation is also investigated. We also study the role of threshold fluctuations
      in the failure of front propagation, both in the fast and slow varying noise
      limits.

PMID- 17500928
TI  - Penetration depth of low-coherence enhanced backscattered light in subdiffusion
      regime.
AB  - The mechanisms of photon propagation in random media in the diffusive multiple
      scattering regime have been previously studied using diffusion approximation.
      However, similar understanding in the low-order (subdiffusion) scattering regime
      is not complete due to difficulties in tracking photons that undergo very few
      scatterings events. Recent developments in low-coherence enhanced backscattering
      (LEBS) overcome these difficulties and enable probing photons that travel very
      short distances and undergo only a few scattering events. In LEBS, enhanced
      backscattering is observed under illumination with spatial coherence length L{sc}
      less than the scattering mean free path l{s}. In order to understand the
      mechanisms of photon propagation in LEBS in the subdiffusion regime, it is
      imperative to develop analytical and numerical models that describe the
      statistical properties of photon trajectories. Here we derive the probability
      distribution of penetration depth of LEBS photons and report Monte Carlo
      numerical simulations to support our analytical results. Our results demonstrate
      that, surprisingly, the transport of photons that undergo low-order scattering
      events has only weak dependence on the optical properties of the medium (l{s} and
      anisotropy factor g) and strong dependence on the spatial coherence length of
      illumination, L{sc} relative to those in the diffusion regime. More importantly,
      these low-order scattering photons typically penetrate less than l{s} into the
      medium due to the low spatial coherence length of illumination and their
      penetration depth is proportional to the one-third power of the coherence volume
      (i.e., [l{s}piL{s}{2}]1/3) .

PMID- 17500929
TI  - Diffusion-trapping model of receptor trafficking in dendrites.
AB  - We present a model for the diffusive trafficking of protein receptors along the
      surface of a neuron's dendrite. Distributed along the dendrite are spatially
      localized trapping regions that represent submicrometer mushroom-like protrusions
      known as dendritic spines. Within these trapping regions receptors can be
      internalized via endocytosis and either reinserted into the surface via
      exocytosis or degraded. We calculate the steady-state distribution of receptors
      along the dendrite assuming a constant flux of receptors inserted at one end,
      adjacent to the soma where receptors are synthesized, and use this to investigate
      the effectiveness of membrane diffusion as a transport mechanism. We also
      calculate the mean first passage time of a receptor to travel a certain distance
      along the cable and use this to derive an effective surface diffusivity.

PMID- 17500930
TI  - Floppy swimming: viscous locomotion of actuated elastica.
AB  - Actuating periodically an elastic filament in a viscous liquid generally breaks
      the constraints of Purcell's scallop theorem, resulting in the generation of a
      net propulsive force. This observation suggests a method to design simple
      swimming devices-which we call "elastic swimmers"-where the actuation mechanism
      is embedded in a solid body and the resulting swimmer is free to move. In this
      paper, we study theoretically the kinematics of elastic swimming. After
      discussing the basic physical picture of the phenomenon and the expected scaling
      relationships, we derive analytically the elastic swimming velocities in the
      limit of small actuation amplitude. The emphasis is on the coupling between the
      two unknowns of the problems-namely the shape of the elastic filament and the
      swimming kinematics-which have to be solved simultaneously. We then compute the
      performance of the resulting swimming device and its dependence on geometry. The
      optimal actuation frequency and body shapes are derived and a discussion of
      filament shapes and internal torques is presented. Swimming using multiple
      elastic filaments is discussed, and simple strategies are presented which result
      in straight swimming trajectories. Finally, we compare the performance of elastic
      swimming with that of swimming micro-organisms.

PMID- 17500931
TI  - Regularizing capacity of metabolic networks.
AB  - Despite their topological complexity almost all functional properties of
      metabolic networks can be derived from steady-state dynamics. Indeed, many
      theoretical investigations (like flux-balance analysis) rely on extracting
      function from steady states. This leads to the interesting question as to how
      metabolic networks avoid complex dynamics and maintain a steady-state behavior.
      Here, we expose metabolic network topologies to binary dynamics generated by
      simple local rules. We find that the networks' response is highly specific:
      Complex dynamics are systematically reduced on metabolic networks compared to
      randomized networks with identical degree sequences. Already small topological
      modifications substantially enhance the capacity of a network to host complex
      dynamic behavior and thus reduce its regularizing potential. This exceptionally
      pronounced regularization of dynamics encoded in the topology may explain why
      steady-state behavior is ubiquitous in metabolism.

PMID- 17500932
TI  - Unified description of poly- and oligonucleotide DNA melting: nearest-neighbor,
      Poland-Sheraga, and lattice models.
AB  - We show that a simple lattice model can provide a unified description of the
      thermal denaturation of DNA oligomers and polymers. The model quantitatively
      reproduces experimental melting curves and reduces in limiting cases to the
      nearest-neighbor model and a suitable modified Poland-Sheraga model. Our results
      support the interpretation of the cooperativity parameter sigma for bubble
      opening in terms of an interfacial (forking) free energy which also affects chain
      opening from the ends. The lattice model treats long-ranged excluded volume
      interactions between all parts of the molecule explicitly, provides access to an
      ensemble of three dimensional structures (and hence the response to external
      mechanical forces), and includes fluctuations in situations without pre
      determined secondary structure.

PMID- 17500933
TI  - Orange reflection from a three-dimensional photonic crystal in the scales of the
      weevil Pachyrrhynchus congestus pavonius (Curculionidae).
AB  - The three-dimensional structure that causes the coloration of the tropical weevil
      Pachyrrhynchus congestus pavonius was studied, using a combination of electron
      microscopy, optical spectroscopy, and numerical modeling. The orange scales that
      cover the colored rings on the animal's body were opened, to display the
      structure responsible for the coloration. This structure is a three-dimensional
      photonic polycrystal, each grain of which showing a face-centered cubic symmetry.
      The measured lattice parameter and the observed filling fraction of this
      structure explain the dominant reflected wavelength in the reddish orange. The
      long-range disorder introduced by the grain boundaries explains the paradoxical
      observation that the reflectance, although generated by a photonic crystal, is
      insensitive to changes in the viewing angle.

PMID- 17500934
TI  - Simulations of intracellular calcium release dynamics in response to a high
      intensity, ultrashort electric pulse.
AB  - Numerical simulations for electrically induced, intracellular calcium release
      from the endoplasmic reticulum are reported. A two-step model is used for self
      consistency. Distributed electrical circuit representation coupled with the
      Smoluchowski equation yields the ER membrane nanoporation for calcium outflow
      based on a numerical simulation. This is combined with the continuum Li-Rinzel
      model and drift diffusion for calcium dynamics. Our results are shown to be in
      agreement with reported calcium release data. A modest increase (rough doubling)
      of the cellular calcium is predicted in the absence of extra-cellular calcium. In
      particular, the applied field of 15 kV/cm with 60 ns pulse duration makes for a
      strong comparison. No oscillations are predicted and the net recovery period of
      about 5 min are both in agreement with published experimental results. A
      quantitative explanation for the lack of such oscillatory behavior, based on the
      density dependent calcium fluxes, is also provided.

PMID- 17500935
TI  - Heteropolymer sequence design and preferential solvation of hydrophilic monomers:
      application of random energy model.
AB  - We study the role of the surface of the globule and the role of interactions with
      the solvent for designed-sequence heteropolymers using the random energy model.
      We investigate the ground-state energy and surface-monomer composition
      distribution. By comparing the freezing transition in random and designed
      sequence heteropolymers, we discuss the effects of design. Based on our results,
      we are able to show under which conditions the solvation effect improves the
      quality of the sequence design. Finally, we study sequence-space entropy and
      discuss the number of available sequences as a function of the imposed
      requirements for design quality.

PMID- 17500936
TI  - Observation of two forms of conformations in the reentrant condensation of DNA.
AB  - Reentrant condensation of DNA in the presence of spermidine (SPD) is studied by
      gel electrophoresis (GEP). It is found that the reentrant condensation of DNA
      induced by SPD can produce a reentrant jamming of DNA molecules at the liquid-gel
      interface during GEP. However, not all the DNA are jammed at the interface
      indicating that there are different forms of condensed DNA. A model of condensed
      DNA consisting of two conformations can be used to explain the experimental
      observations. A phase diagram of the reentrant condensation based on the jamming
      states of DNA in terms of the length of DNA (L) and concentration of SPD is
      constructed. Furthermore, no charge inversion is observed during the reentrant
      transition.

PMID- 17500937
TI  - Escape through an unstable limit cycle driven by multiplicative colored non
      Gaussian and additive white Gaussian noises.
AB  - In a previous paper [Bag and Hu, Phys. Rev. E 73, 061107 (2006)], we studied the
      mean lifetime (MLT) for the escape of a Brownian particle through an unstable
      limit cycle driven by multiplicative colored Gaussian and additive Gaussian white
      noises and found resonant activation (RA) behavior. In the present paper we
      switch from Gaussian to non-Gaussian multiplicative colored noise. We find that
      in the RA phenomenon, the minimum appears at a smaller noise correlation time
      (tau) for non-Gaussian noises compared to Gaussian noises in the plot of MLT vs
      tau for a fixed noise variance; the same plot for a given noise strength
      increases linearly and the increasing rate is smaller for non-Gaussian noises
      than for the Gaussian noises; the plot of logarithm of inverse of MLT vs inverse
      of the strength of additive noise is Arrhenius-like for Gaussian colored noise
      and it becomes similar to the quantum-Kramers rate if the multiplicative noise is
      non-Gaussian.

PMID- 17500938
TI  - Anomalous diffusion induced by a Mittag-Leffler correlated noise.
AB  - We introduce a Mittag-Leffler correlated random force leading to anomalous
      diffusion. Starting from a generalized Langevin equation, and using Laplace
      analysis we derive exact expressions for the mean values, variances and diffusion
      coefficient for a free particle in terms of generalized Mittag-Leffler functions
      and its derivatives. The asymptotic behavior of these quantities are obtained,
      from which the anomalous diffusion behavior of the particle is displayed.

PMID- 17500939
TI  - Double domain structure of the pair contact process with diffusion.
AB  - We investigate the domain structure of the pair contact process with diffusion
      (PCPD). PCPD is a stochastic reaction-diffusion model which evolves by the
      competition of two binary reactions, 2A-->3A and 2A-->0 . In addition, each
      particle diffuses isotropically, which leads to the bidirectional coupling
      between solitary particles and pairs. The spreading domain formed from localized
      activities in vacuum consists of two regions: The coupled region of size R{p}
      where pairs and solitary particles coexist and the uncoupled region of size R{U}
      where only solitary particles exist, respectively. The size of the whole domain R
      is given as R=R{p}+R{U} . At criticality, R{p} and R{U} scale as R{p}
      approximately t(1/Z{p}) and R{U} approximately t(1/Z{U}) with Z{U}>Z{p}. We
      estimate Z{p}=1.61(1) and Z{U}=1.768(8) . Hence the correction to the scaling of
      R,Q=R{U}/R{p} slowly decays extremely, which makes it practically impossible to
      identify the asymptotic scaling behavior of R. The double domain structure is
      another reason for the extremely slow approach to the asymptotic scaling regime
      of PCPD.

PMID- 17500940
TI  - Memory effect in the adsorption phenomena of neutral particles.
AB  - The adsorption-desorption phenomenon of neutral particles dissolved in an
      isotropic fluid is investigated by using a nonsingular kernel in the kinetic
      equation at the limiting surfaces. To account for the relevance of a memory
      effect, three types of kernels in the kinetic equation are considered. Similar
      kernels have been used to investigate nonexponential relaxation including several
      contexts such as dielectric relaxation, diffusion-controlled relaxation in
      liquids, liquid crystals, and amorphous polymers. A suitable choice for a
      temporal kernel can account for the relative importance of physisorption or
      chemisorption, according to the time scale governing the adsorption phenomena,
      and can be the key mechanism to understand the specific roles of both processes.
      By using a general procedure, the time evolution of the density of particles is
      determined in closed analytical form. The analysis is relevant in the description
      of the adsorption phenomena in general.

PMID- 17500941
TI  - Migration of a bubble in front of a directionally solidified interface.
AB  - We examine the quasistatic thermocapillary migration of a gas bubble normal to a
      solidified interface. The analysis accounts for the deformation of the solid
      liquid interface caused by the bubble's presence. An expression for the distance
      between the bubble surface and the crystal-melt interface is derived, and used to
      quantify the dependence of the bubble's migration velocity on the processing
      variables and material properties of the directional solidification process.

PMID- 17500942
TI  - Discontinuous change in the smectic layer thickness in ferrielectric liquid
      crystals.
AB  - The temperature dependence of the thickness of thick free-standing films is
      studied using a high-resolution film thickness measurement technique. A small
      discontinuity in the temperature dependence of the smectic layer thickness at
      every phase transition between ferro-, ferri-, and antiferroelectric phases is
      observed. We show that the major contribution to it arises from a change in the
      smectic tilt angle.

PMID- 17500943
TI  - Nonlocal competition and front propagation in branching-coalescence systems.
AB  - The spatial invasion of a stable into an unstable phase is studied for the
      branching-coalescence process with nonlocal competition. Numerical experiments
      show that the threshold at the front leading edge, introduced by the discreteness
      of the reactants, allows for the nonlocal competition to affect the front
      velocity. However, the front still moves ballistically after a short transient
      period for any finite range competition length.

PMID- 17500944
TI  - Comment on "Packing hyperspheres in high-dimensional Euclidean spaces".
AB  - It is shown that the numerical results of Skoge [Phys. Rev. E 74, 041127 (2006)]
      are in very good agreement with the theoretical predictions of Parisi and Zamponi
      [J. Stat. Mech.: Theory Exp. (2006) P03017].

PMID- 17500945
TI  - Randomness enhances cooperation: a resonance-type phenomenon in evolutionary
      games.
AB  - We investigate the effect of randomness in both relationships and decisions on
      the evolution of cooperation. Simulation results show, in such randomness'
      presence, the system evolves more frequently to a cooperative state than in its
      absence. Specifically, there is an optimal amount of randomness, which can induce
      the highest level of cooperation. The mechanism of randomness promoting
      cooperation resembles a resonancelike fashion, which could be of particular
      interest in evolutionary game dynamics in economic, biological, and social
      systems.

PMID- 17500946
TI  - Detecting complex network modularity by dynamical clustering.
AB  - Based on cluster desynchronization properties of phase oscillators, we introduce
      an efficient method for the detection and identification of modules in complex
      networks. The performance of the algorithm is tested on computer generated and
      real-world networks whose modular structure is already known or has been studied
      by means of other methods. The algorithm attains a high level of precision,
      especially when the modular units are very mixed and hardly detectable by the
      other methods, with a computational effort O(KN) on a generic graph with N nodes
      and K links.

PMID- 17500947
TI  - Transport and percolation theory in weighted networks.
AB  - We study the distribution P(sigma) of the equivalent conductance sigma for Erdos
      Renyi (ER) and scale-free (SF) weighted resistor networks with N nodes. Each link
      has conductance g triple bond e-ax, where x is a random number taken from a
      uniform distribution between 0 and 1 and the parameter a represents the strength
      of the disorder. We provide an iterative fast algorithm to obtain P(sigma) and
      compare it with the traditional algorithm of solving Kirchhoff equations. We
      find, both analytically and numerically, that P(sigma) for ER networks exhibits
      two regimes: (i) A low conductance regime for sigma<e-apc, where pc=1/(k) is the
      critical percolation threshold of the network and k is the average degree of the
      network. In this regime P(sigma) is independent of N and follows the power law
      P(sigma) approximately sigma-alpha, where alpha=1-(ka)/a. (ii) A high conductance
      regime for sigma>e-apc in which we find that P(sigma) has strong N dependence and
      scales as P(sigma) approximately f(sigma,apc/N1/3) . For SF networks with degree
      distribution P(k) approximately k-lambda, kmin<or=k<or=kmax, we find numerically
      also two regimes, similar to those found for ER networks.

PMID- 17500948
TI  - Improving immunization strategies.
AB  - We introduce an immunization method where the percentage of required vaccinations
      for immunity are close to the optimal value of a targeted immunization scheme of
      highest degree nodes. Our strategy retains the advantage of being purely local,
      without the need for knowledge on the global network structure or identification
      of the highest degree nodes. The method consists of selecting a random node and
      asking for a neighbor that has more links than himself or more than a given
      threshold and immunizing him. We compare this method to other efficient
      strategies on three real social networks and on a scale-free network model and
      find it to be significantly more effective.

PMID- 17500949
TI  - Dissipative self-organized branching in a dynamic population.
AB  - We study a locally nonconservative self-organized branching process (SOBP) in an
      open system of excitable agents exhibiting spontaneous excitation and
      deexcitation. The SOBP achieves criticality even in the absence of energy
      conservation as the population relaxes to a stable state with no overexcited
      agent. Criticality is widely thought to happen only in a locally conservative
      SOBP. Our model explains the observed characteristic size in the size
      distribution of tuna fish schools and the neuronal avalanches in cortical
      networks.

PMID- 17500950
TI  - Synthesizing folded band chaos.
AB  - A randomly driven linear filter that synthesizes Lorenz-like, reverse-time chaos
      is shown also to produce Rossler-like folded band wave forms when driven using a
      different encoding of the random source. The relationship between the topological
      entropy of the random source, dissipation in the linear filter, and the positive
      Lyapunov exponent for the reverse-time wave form is exposed. The two drive
      encodings are viewed as grammar restrictions on a more general encoding that
      produces a chaotic superset encompassing both the Lorenz butterfly and Rossler
      folded band paradigms of nonlinear dynamics.

PMID- 17500951
TI  - Chaos in a one-dimensional compressible flow.
AB  - We study the dynamics of a one-dimensional discrete flow with open boundaries--a
      series of moving point particles connected by ideal springs. These particles flow
      towards an inlet at constant velocity, pass into a region where they are free to
      move according to their nearest neighbor interactions, and then pass an outlet
      where they travel with a sinusoidally varying velocity. As the amplitude of the
      outlet oscillations is increased, we find that the resident time of particles in
      the chamber follows a bifurcating (Feigenbaum) route to chaos. This irregular
      dynamics may be related to the complex behavior of many particle discrete flows
      or is possibly a low-dimensional analogue of nonstationary flow in continuous
      systems.

PMID- 17500952
TI  - Extensive chaos in Rayleigh-Benard convection.
AB  - Using large-scale numerical calculations we explore spatiotemporal chaos in
      Rayleigh-Benard convection for experimentally relevant conditions. We calculate
      the spectrum of Lyapunov exponents and the Lyapunov dimension describing the
      chaotic dynamics of the convective fluid layer at constant thermal driving over a
      range of finite system sizes. Our results reveal that the dynamics of fluid
      convection is truly chaotic for experimental conditions as illustrated by a
      positive leading-order Lyapunov exponent. We also find the chaos to be extensive
      over the range of finite-sized systems investigated as indicated by a linear
      scaling between the Lyapunov dimension of the chaotic attractor and the system
      size.

PMID- 17500953
TI  - Optimal main pulse angle for different preplasma conditions in transient
      collisionally pumped x-ray lasers.
AB  - The effects of the incidence angle of the main pump (MP) pulse in non-normal
      pumping geometry and the influence of the MP duration are investigated
      experimentally and theoretically for a transient collisionally pumped (TCE) x-ray
      laser in Ni-like Zr at 45 degrees and 72 degrees incidence angle on the target.
      The way they transfer to the x-ray laser output depends on the preplasma
      conditions, most notably on the average ionization distribution at the arrival of
      the MP. Moreover, contrary to previous grazing incidence pumping results, it is
      found that the shortest attainable MP maximizes the output. Modeling of the
      experimental results is performed with EHYBRID code. The results are important
      for scaling high repetition-rate non-normal incidence pumped lasers to sub- 10nm
      wavelengths.

PMID- 17500954
TI  - Chaotic bound state of localized structures in the complex Ginzburg-Landau
      equation.
AB  - Stable dynamic bound states of dissipative localized structures are found. It is
      characterized by chaotic oscillations of distance between the localized
      structures, their phase difference, and the center of mass velocity.

PMID- 17500955
TI  - Failure avalanches in fiber bundles for discrete load increase.
AB  - The statistics of burst avalanche sizes n during failure processes in a fiber
      bundle follows a power law D(n) approximately n-xi for large avalanches. The
      exponent xi depends upon how the avalanches are provoked. While it is known that
      when the load on the bundle is increased in a continuous manner the exponent
      takes the value xi=52 , we show that when the external load is increased in
      discrete and not too small steps, the exponent value xi=3 is relevant. Our
      analytic treatment applies to bundles with a general probability distribution of
      the breakdown thresholds for the individual fibers. The preasymptotic size
      distribution of avalanches is also considered.

PMID- 17500956
TI  - Diversity of graphs with highly variable connectivity.
AB  - A popular approach for describing the structure of many complex networks focuses
      on graph theoretic properties that characterize their large-scale connectivity.
      While it is generally recognized that such descriptions based on aggregate
      statistics do not uniquely characterize a particular graph and also that many
      such statistical features are interdependent, the relationship between competing
      descriptions is not entirely understood. This paper lends perspective on this
      problem by showing how the degree sequence and other constraints (e.g.,
      connectedness, no self-loops or parallel edges) on a particular graph play a
      primary role in dictating many features, including its correlation structure.
      Building on recent work, we show how a simple structural metric characterizes key
      differences between graphs having the same degree sequence. More broadly, we show
      how the (often implicit) choice of a background set against which to measure
      graph features has serious implications for the interpretation and comparability
      of graph theoretic descriptions.

PMID- 17500957
TI  - Controllability of complex networks via pinning.
AB  - We study the problem of controlling a general complex network toward an assigned
      synchronous evolution by means of a pinning control strategy. We define the
      pinning controllability of the network in terms of the spectral properties of an
      extended network topology. The roles of the control and coupling gains, as well
      as of the number of pinned nodes, are also discussed.

PMID- 17500958
TI  - Load capacity and rupture displacement in viscoelastic fiber bundles.
AB  - We study the creep rupture of viscoelastic fiber bundles under uniaxial constant
      tensile loading, assuming global load sharing (GLS) for the redistribution of
      load following fiber failure. We consider loading paths such that the stress
      raises to a value sigma0 under a time-independent loading (negligible creep
      strain) and remains fixed thereafter. Motivated by experimental observations, we
      introduce an "effective" strain controlled failure criterion to incorporate
      damage into the system, thus damage is distributed over time. In addition, when a
      "limit" value for the effective stress is reached, failure of the remaining alive
      fibers is instantaneous. This enables us to show both analytically and
      numerically that creep rupture occurs for external loads above a critical value
      that is less than the static fracture bundle's strength in accordance with
      experimental observations. An analytical expression for this critical load is
      given. For stress levels below the critical value, the system suffers only
      partial failure since the deformation tends to a stationary solution for which
      the effective stress is below the limit value giving rise to an infinite
      lifetime. On the other hand, if the time-independent loading process ends in the
      softening regime, the deformation of the system monotonically increases in time
      resulting in global failure at finite time irrespectively of the applied load.
      Moreover, the applied model is found to be consistent with the experimentally
      observed increase of the creep rupture displacement with decreasing steady
      external load (above the critical value).

PMID- 17500959
TI  - Effect of initial conditions on Glauber dynamics in complex networks.
AB  - The effect of initial spin configurations on zero-temperature Glauber spin
      dynamics in complex networks is investigated. In a system in which the initial
      spins are defined by centrality measures at the vertices of a network, a variety
      of nontrivial diffusive behaviors arise, particularly in relation to functional
      relationships between the initial and final fractions of positive spins, some of
      which exhibit a critical point. Notably, the majority spin in the initial state
      is not always dominant in the final state and the phenomena that occur as a
      result of the dynamics differ according to the initial condition, even for the
      same network. It is thus concluded that the initial condition of a complex
      network exerts an influence on spin dynamics that is equally as strong as that
      exerted by the network structure.

PMID- 17500960
TI  - Dynamics of rough surfaces generated by two-dimensional lattice spin models.
AB  - We present an analysis of mapped surfaces obtained from configurations of two
      classical statistical-mechanical spin models in the square lattice: the q -state
      Potts model and the spin-1 Blume-Capel model. We carry out a study of the phase
      transitions in these models using the Monte Carlo method and a mapping of the
      spin configurations to a solid-on-solid growth model. The first- and second-order
      phase transitions and the tricritical point happen to be relevant in the kinetic
      roughening of the surface growth process. At the low and high temperature phases
      the roughness W grows indefinitely with the time, with growth exponent beta(w)
      approximately 0.50(W approximately tbeta(w)) . At criticality the growth presents
      a crossover at a characteristic time tc, from a correlated regime (with beta(w)
      ++ 0.50 ) to an uncorrelated one (beta(w) approximately equal 0.50) . We also
      calculate the Hurst exponent H of the corresponding surfaces. At criticality,
      beta(w) and H have values characteristic of correlated growth, distinguishing
      second- from first-order phase transitions. It has also been shown that the
      Family-Vicsek relation for the growth exponents also holds for the noise-reduced
      roughness with an anomalous scaling.

PMID- 17500961
TI  - Percolation theory applied to measures of fragmentation in social networks.
AB  - We apply percolation theory to a recently proposed measure of fragmentation F for
      social networks. The measure F is defined as the ratio between the number of
      pairs of nodes that are not connected in the fragmented network after removing a
      fraction q of nodes and the total number of pairs in the original fully connected
      network. We compare F with the traditional measure used in percolation theory,
      P(infinity), the fraction of nodes in the largest cluster relative to the total
      number of nodes. Using both analytical and numerical methods from percolation, we
      study Erdos-Renyi and scale-free networks under various types of node removal
      strategies. The removal strategies are random removal, high degree removal, and
      high betweenness centrality removal. We find that for a network obtained after
      removal (all strategies) of a fraction q of nodes above percolation threshold,
      P(infinity) approximately (1-F)1/2. For fixed P(infinity) and close to
      percolation threshold (q=qc), we show that 1-F better reflects the actual
      fragmentation. Close to qc, for a given P(infinity), 1-F has a broad distribution
      and it is thus possible to improve the fragmentation of the network. We also
      study and compare the fragmentation measure F and the percolation measure
      P(infinity) for a real social network of workplaces linked by the households of
      the employees and find similar results.

PMID- 17500962
TI  - Competition between the catalyzed birth and death in the exchange-driven growth.
AB  - We propose a three-species ( A , B , and C ) exchange-driven aggregate growth
      model with competition between catalyzed birth and catalyzed death. In the
      system, exchange-driven aggregation occurs between any two aggregates of the same
      species with the size-dependent rate kernel Kn(k,j)=Knkj (n=1,2,3) , and,
      meanwhile, monomer birth and death of species A occur under the catalysis of
      species B and C with the catalyzed birth and catalyzed death rate kernels
      I(k,j)=Ikjv and J(k,j)=Jkjv , respectively. The kinetic behavior is investigated
      by means of the mean-field rate equation approach. The form of the aggregate size
      distribution ak(t) of species A is found to depend crucially on the competition
      between species- B -catalyzed birth of species A and species- C -catalyzed death
      of species A , as well as the exchange-driven growth. The results show that (i)
      when exchange-driven aggregation dominates the process, ak(t) satisfies the
      conventional scaling form; (ii) when catalyzed birth dominates the process, ak(t)
      takes the conventional or generalized scaling form; and (iii) when catalyzed
      death dominates the process, the aggregate size distribution of species A evolves
      only according to some modified scaling forms.

PMID- 17500963
TI  - Dynamics of crowd disasters: an empirical study.
AB  - Many observations of the dynamics of pedestrian crowds, including various self
      organization phenomena, have been successfully described by simple many-particle
      models. For ethical reasons, however, there is a serious lack of experimental
      data regarding crowd panic. Therefore, we have analyzed video recordings of the
      crowd disaster in Mina/Makkah during the Hajj in 1426H on 12 January 2006. They
      reveal two subsequent, sudden transitions from laminar to stop-and-go and
      "turbulent" flows, which question many previous simulation models. While the
      transition from laminar to stop-and-go flows supports a recent model of
      bottleneck flows [D. Helbing, Phys. Rev. Lett. 97, 168001 (2006)], the subsequent
      transition to turbulent flow is not yet well understood. It is responsible for
      sudden eruptions of pressure release comparable to earthquakes, which cause
      sudden displacements and the falling and trampling of people. The insights of
      this study into the reasons for critical crowd conditions are important for the
      organization of safer mass events. In particular, they allow one to understand
      where and when crowd accidents tend to occur. They have also led to
      organizational changes, which have ensured a safe Hajj in 1427H.

PMID- 17500964
TI  - Extreme times for volatility processes.
AB  - Extreme times techniques, generally applied to nonequilibrium statistical
      mechanical processes, are also useful for a better understanding of financial
      markets. We present a detailed study on the mean first-passage time for the
      volatility of return time series. The empirical results extracted from daily data
      of major indices seem to follow the same law regardless of the kind of index thus
      suggesting an universal pattern. The empirical mean first-passage time to a
      certain level L is fairly different from that of the Wiener process showing a
      dissimilar behavior depending on whether L is higher or lower than the average
      volatility. All of this indicates a more complex dynamics in which a reverting
      force drives volatility toward its mean value. We thus present the mean first
      passage time expressions of the most common stochastic volatility models whose
      approach is comparable to the random diffusion description. We discuss asymptotic
      approximations of these models and confront them to empirical results with a good
      agreement with the exponential Ornstein-Uhlenbeck model.

PMID- 17500965
TI  - Exploring the assortativity-clustering space of a network's degree sequence.
AB  - Nowadays there is a multitude of measures designed to capture different aspects
      of network structure. To be able to say if a measured value is expected or not,
      one needs to compare it with a reference model (null model). One frequently used
      null model is the ensemble of graphs with the same set of degrees as the original
      network. Here, we argue that this ensemble can give more information about the
      original network than effective values of network structural quantities. By
      mapping out this ensemble in the space of some low-level network structure--in
      our case, those measured by the assortativity and clustering coefficients--one
      can, for example, study where in the valid region of the parameter space the
      observed networks are. Such analysis suggests which quantities (or combination of
      quantities) are actively optimized during the evolution of the network. We use
      four very different biological networks to exemplify our method. Among other
      things, we find that high clustering might be a force in the evolution of protein
      interaction networks. We also find that all four networks are conspicuously
      robust to both random errors and targeted attacks.

PMID- 17500966
TI  - Cellular automaton simulation of pedestrian counter flow considering the
      surrounding environment.
AB  - This paper presents a cellular automaton model without step back to simulate the
      pedestrian counter flow in a channel. The consideration of the surrounding
      environment when people make judgments on moving directions is added to a random
      walker model also without step back. Two types of walkers: the right walkers
      going to the right and the left walkers going to the left are taken into account.
      The characteristics of counterflow are clarified. Influences of the different
      interaction radius values and system sizes on movement are studied. Phase
      transition from free moving to jamming is observed with the increase of entrance
      density. It is found that the critical entrance density pc at the transition
      point does not depend on the system size when the interaction radius value is
      large. Simulation results are represented as a comparison with the random walker
      model.

PMID- 17500967
TI  - Response of degree-correlated scale-free networks to stimuli.
AB  - The response of degree-correlated scale-free attractor networks to stimuli is
      studied. We show that degree-correlated scale-free networks are robust to random
      stimuli as well as the uncorrelated scale-free networks, while assortative
      (disassortative) scale-free networks are more (less) sensitive to directed
      stimuli than uncorrelated networks. We find that the degree correlation of scale
      free networks makes the dynamics of attractor systems different from uncorrelated
      ones. The dynamics of correlated scale-free attractor networks results in the
      effects of degree correlation on the response to stimuli.

PMID- 17500968
TI  - Statistical properties of sampled networks by random walks.
AB  - We study the statistical properties of the sampled networks by a random walker.
      We compare topological properties of the sampled networks such as degree
      distribution, degree-degree correlation, and clustering coefficient with those of
      the original networks. From the numerical results, we find that most of
      topological properties of the sampled networks are almost the same as those of
      the original networks for gamma les approximately <3. In contrast, we find that
      the degree distribution exponent of the sampled networks for gamma>3 somewhat
      deviates from that of the original networks when the ratio of the sampled network
      size to the original network size becomes smaller. We also apply the sampling
      method to various real networks such as collaboration of movie actor, Worldwide
      Web, and peer-to-peer networks. All topological properties of the sampled
      networks are essentially the same as those of the original real networks.

PMID- 17500969
TI  - Computer simulation of fatigue under diametrical compression.
AB  - We study the fatigue fracture of disordered materials by means of computer
      simulations of a discrete element model. We extend a two-dimensional fracture
      model to capture the microscopic mechanisms relevant for fatigue and we simulate
      the diametric compression of a disc shape specimen under a constant external
      force. The model allows us to follow the development of the fracture process on
      the macrolevel and microlevel varying the relative influence of the mechanisms of
      damage accumulation over the load history and healing of microcracks. As a
      specific example we consider recent experimental results on the fatigue fracture
      of asphalt. Our numerical simulations show that for intermediate applied loads
      the lifetime of the specimen presents a power law behavior. Under the effect of
      healing, more prominent for small loads compared to the tensile strength of the
      material, the lifetime of the sample increases and a fatigue limit emerges below
      which no macroscopic failure occurs. The numerical results are in a good
      qualitative agreement with the experimental findings.

PMID- 17500970
TI  - Understanding the complex dynamics of stock markets through cellular automata.
AB  - We present a cellular automaton (CA) model for simulating the complex dynamics of
      stock markets. Within this model, a stock market is represented by a two
      dimensional lattice, of which each vertex stands for a trader. According to
      typical trading behavior in real stock markets, agents of only two types are
      adopted: fundamentalists and imitators. Our CA model is based on local
      interactions, adopting simple rules for representing the behavior of traders and
      a simple rule for price updating. This model can reproduce, in a simple and
      robust manner, the main characteristics observed in empirical financial time
      series. Heavy-tailed return distributions due to large price variations can be
      generated through the imitating behavior of agents. In contrast to other
      microscopic simulation (MS) models, our results suggest that it is not necessary
      to assume a certain network topology in which agents group together, e.g., a
      random graph or a percolation network. That is, long-range interactions can
      emerge from local interactions. Volatility clustering, which also leads to heavy
      tails, seems to be related to the combined effect of a fast and a slow process:
      the evolution of the influence of news and the evolution of agents' activity,
      respectively. In a general sense, these causes of heavy tails and volatility
      clustering appear to be common among some notable MS models that can confirm the
      main characteristics of financial markets.

PMID- 17500971
TI  - Growing networks under geographical constraints.
AB  - Inspired by the structure of technological weblike systems, we discuss network
      evolution mechanisms which give rise to topological properties found in real
      spatial networks. Thus, we suggest that the peculiar structure of transport and
      distribution networks is fundamentally determined by two factors. These are the
      dependence of the spatial interaction range of vertices on the vertex
      attractiveness (or importance within the network) and on the inhomogeneous
      distribution of vertices in space. We propose and analyze numerically a simple
      model based on these generating mechanisms which seems, for instance, to be able
      to reproduce known structural features of the Internet.

PMID- 17500972
TI  - When are projections also embeddings?
AB  - We study an autonomous four-dimensional dynamical system used to model certain
      geophysical processes. This system generates a chaotic attractor that is strongly
      contracting, with four Lyapunov exponents lambdai that satisfy
      lambda1+lambda2+lambda3<0 , so the Lyapunov dimension is DL=2+|lambda3|/lambda1<3
      in the range of coupling parameter values studied. As a result, it should be
      possible to find three-dimensional spaces in which the attractors can be embedded
      so that topological analyses can be carried out to determine which stretching and
      squeezing mechanisms generate chaotic behavior. We study mappings into R3 to
      determine which can be used as embeddings to reconstruct the dynamics. We find
      dramatically different behavior in the two simplest mappings: projections from R4
      to R3 . In one case the one-parameter family of attractors studied remains
      topologically unchanged for all coupling parameter values. In the other case,
      during an intermediate range of parameter values the projection undergoes self
      intersections, while the embedded attractors at the two ends of this range are
      topologically mirror images of each other.

PMID- 17500973
TI  - Statistical properties of experimental coherent waves in microcavity lasers:
      analogous study of quantum billiard wave functions.
AB  - We use a microcavity laser to explore the properties of experimental coherent
      waves as an analogous study of the chaotic wave functions in quantum billiards.
      With the eigenstate expansion method, the experimental high-order chaotic
      coherent waves are well reconstructed. The reconstructed wave functions are
      employed to calculate the field and intensity correlations. It is found that the
      spreading of k-space (momentum space) distribution leads to not only wave
      localization in coordinate space but also enhancement of long-range correlations.

PMID- 17500974
TI  - Selection mechanism for rotating patterns in weakly excitable media.
AB  - Two types of patterns rigidly rotating within a disk of a weakly excitable medium
      are studied using the free-boundary approach. The patterns are spots moving along
      the boundary of the disk and spiral waves rotating around the disk center. The
      study reveals a selection mechanism that uniquely determines the shape and the
      angular velocity of these patterns as a function of the medium excitability and
      the disk radius. These two types of patterns coexist below some critical
      parameter value, coincide at a bifurcation point, and do not exist above it. The
      same selection mechanism is applied to describe a limiting case of a spiral wave
      rotating in an unbounded medium.

PMID- 17500975
TI  - Leaking billiards.
AB  - Billiards are idealizations for systems where particles or waves are confined to
      cavities, or to other homogeneous regions. In billiard systems a point particle
      moves freely except for specular reflections from rigid walls. However, billiard
      walls are not always completely reflective and measurements inside can also open
      the billiard. Since boundary openings have been studied extensively in the
      literature, we rather model leakages inside the billiard. In particular, we
      investigate the classical dynamics of a leakage for a continuous family of
      billiard systems, that is, the stadium-lemon-billiard family. With a single
      parameter the geometry of the billiard can be tuned from stadium (being fully
      hyperbolic) over circle (integrable) to the lemon-shaped billiard (mixed
      chaotic). For the stadium billiard we found an algebraically decaying mean escape
      time with the linear size of the leakage n(esc) approximately epsilon-1 together
      with an exponential decay of the survival probability distribution. The finding
      is nearly independent of the position and size of the leakage, as long as the
      leakage is much smaller than the system size, and it is in good agreement with a
      stochastic map approximation of the dynamics. Due to the mixed phase space for
      lemon billiards, the mean escape time depends both on the position and geometry
      of the leakage. For systems where quasiregular motion dominates, we found a
      linear dependence of the mean escape time, n(esc) approximately 1-epsilon, which
      we refer to as flooding law. Our findings are helpful in understanding dynamics
      of leaking Hamiltonian systems.

PMID- 17500976
TI  - Noise sensitivity of phase-synchronization time in stochastic resonance: theory
      and experiment.
AB  - Recent numerical and heuristic arguments have revealed that the average phase
      synchronization time between the input and the output associated with stochastic
      resonance is highly sensitive to noise variation. In particular there is evidence
      that this average time exhibits a cusplike behavior as the noise strength varies
      through the optimal value. Here we present an explicit formula for the average
      phase-synchronization time in terms of the phase diffusion coefficient and the
      average frequency difference between the input and the output signals. We also
      provide experimental evidence for the cusplike behavior by using a bistable
      microelectronic-circuit system.

PMID- 17500977
TI  - Conversion of stability in systems close to a Hopf bifurcation by time-delayed
      coupling.
AB  - We propose a control method with time delayed coupling which makes it possible to
      convert the stability features of systems close to a Hopf bifurcation. We
      consider two delay-coupled normal forms for Hopf bifurcation and demonstrate the
      conversion of stability, i.e., an interchange between the sub- and supercritical
      Hopf bifurcation. The control system provides us with an unified method for
      stabilizing both the unstable periodic orbit and the unstable steady state and
      reveals typical effects like amplitude death and phase locking. The main method
      and the results are applicable to a wide class of systems showing Hopf
      bifurcations, for example, the Van der Pol oscillator. The analytical theory is
      supported by numerical simulations of two delay-coupled Van der Pol oscillators,
      which show good agreement with the theory.

PMID- 17500978
TI  - Isochronal synchronization of delay-coupled systems.
AB  - We consider small network models for mutually delay-coupled systems which
      typically do not exhibit stable isochronally synchronized solutions. We show
      analytically and numerically that for certain coupling architectures which
      involve delayed self-feedback to the nodes, the oscillators become isochronally
      synchronized. Applications are shown for both incoherent pump-coupled lasers and
      spatiotemporal coupled fiber ring lasers.

PMID- 17500980
TI  - Mixing efficiency in an excitable medium with chaotic shear flow.
AB  - The effect of a time-periodic chaotic shear flow on an excitable chemical medium
      is studied numerically. Stirring effects on pattern formation strongly depend on
      the shear amplitude and the ratio of the advective and chemical time scales
      (Damkohler number, Da). We have observed that the wave period increases with
      decreasing Da below some critical value, afterwards the period decreases until
      complete wave annihilation. In the last case, before final extinction, a set of
      uncorrelated, nonstationary excitable dots survive, whose number depends on the
      mixing rate. Insights on the nature of this critical behavior are obtained
      through the calculation of the mixing efficiency of the flow.

PMID- 17500979
TI  - Influence of parametric forcing on the nonequilibrium dynamics of wave patterns.
AB  - We investigate analytically and numerically the effect of inhomogeneities on the
      nonequilibrium dynamics of wave patterns in the framework of a complex Ginzburg
      Landau equation (CGLE) with parametric, nonresonant forcing periodic in space and
      time. It is found that the forcing results in occurrence of traveling waves with
      different dispersion properties. In the limiting case of forcing with very large
      wavelength, the waves have essentially anharmonic spatial structure. We consider
      the influence of modulations on the development of an intermittent chaos and show
      that the parametric forcing may completely suppress the appearance of chaotic
      patterns. The relations between this and other pattern-forming systems are
      discussed. The results obtained are applied to describe the dynamics of thermal
      Rossby waves influenced by surface topography.

PMID- 17500981
TI  - Morphological stability of electromigration-driven vacancy islands.
AB  - The electromigration-induced shape evolution of two-dimensional vacancy islands
      on a crystal surface is studied using a continuum approach. We consider the
      regime where mass transport is restricted to terrace diffusion in the interior of
      the island. In the limit of fast attachment (detachment) kinetics a circle
      translating at constant velocity is a stationary solution of the problem. In
      contrast to earlier work [O. Pierre-Louis and T. L. Einstein, Phys. Rev. B 62,
      13697 (2000)], we show that the circular solution remains linearly stable for
      arbitrarily large driving forces. The numerical solution of the full nonlinear
      problem nevertheless reveals a fingering instability at the trailing end of the
      island, which develops from finite amplitude perturbations and eventually leads
      to pinch off. Relaxing the condition of instantaneous attachment (detachment)
      kinetics, we obtain noncircular elongated stationary shapes in an analytic
      approximation that compares favorably to the full numerical solution.

PMID- 17500982
TI  - Geometrically driven wrinkling observed in free plastic sheets and leaves.
AB  - We have measured the multiscale wrinkling that occurs along the edge of torn
      plastic sheets. The plastic deformations produced by tearing define a new metric
      on the sheet, which then relaxes elastically. The resultant patterns of wrinkles
      correspond to a superposition of waves of different wavelengths. Measurements of
      the variation of the pattern as a function of the distance from the edge reveal a
      set of transitions, each of which adds a new mode to the cascade. The wavelengths
      lambda in the cascade depend on both a geometrical length scale Lgeo given by the
      metric near the sheet's edge, and the sheet thickness t: lambda proportional
      t0.3Lgeo0.7. This scaling implies vanishingly short wavelengths in the limit t-
      >0 . A possible geometrical origin of this behavior is discussed. Finally, we
      show that our measurement and analysis techniques are applicable to the study of
      some wavy patterns of leaves. These measurements reveal that the intrinsic
      geometry of a wavy leaf resembles that of the torn plastic sheets. This supports
      the possibility that some leaves form waves through a spontaneous wrinkling,
      rather than through an explicit three-dimensional construction.

PMID- 17500983
TI  - Turing patterns in three dimensions.
AB  - We investigate three-dimensional Turing patterns in two-component reaction
      diffusion systems. The FitzHugh-Nagumo equation, the Brusselator, and the Gray
      Scott model are solved numerically in three dimensions. Several interconnected
      structures of domains as well as lamellar, hexagonal, and spherical domains are
      obtained as stable motionless equilibrium patterns. The relative stability of
      these structures is studied analytically based on the reduction approximation.
      The relation with the microphase-separated structures in block copolymers is also
      discussed.

PMID- 17500984
TI  - Stability of localized solutions in a subcritically unstable pattern-forming
      system under a global delayed control.
AB  - The formation of spatially localized patterns in a system with subcritical
      instability under feedback control with delay is investigated within the
      framework of globally controlled Ginzburg-Landau equation. It is shown that
      feedback control can stabilize spatially localized solutions. With the increase
      of delay, these solutions undergo oscillatory instability that, for large enough
      control strength, results in the formation of localized oscillating pulses. With
      further increase of the delay the solution blows up.

PMID- 17500985
TI  - Vertical chaos and horizontal diffusion in the bouncing-ball billiard.
AB  - The bouncing-ball billiard is a low-dimensional system with which transport
      properties of real physical systems can be studied theoretically. We study the
      bouncing-ball billiard with nonconvex scatterers and small slopes. We show that
      between the horizontal and vertical motion there is a separation of time scales,
      which is controlled by the slope of the billiard. We apply the theory of time
      scale separation developed by Kantz Physica D 187, 200 (2004). If the vertical
      motion is chaotic, the horizontal motion is diffusive, but if the vertical motion
      is (quasi)periodic, there is no diffusion. We confirm the results with numerical
      simulations. Hence, the order-chaos transition in the vertical degrees of freedom
      translates into a localization-delocalization transition for the horizontal
      motion.

PMID- 17500986
TI  - Approximating chaotic saddles for delay differential equations.
AB  - Chaotic saddles are unstable invariant sets in the phase space of dynamical
      systems that exhibit transient chaos. They play a key role in mediating transport
      processes involving scattering and chaotic transients. Here we present evidence
      (long chaotic transients and fractal basins of attraction) of transient chaos in
      a "logistic" delay differential equation. We adapt an existing method (stagger
      and-step) to numerically construct the chaotic saddle for this system. This is
      the first such analysis of transient chaos in an infinite-dimensional dynamical
      system, and in delay differential equations in particular. Using Poincare section
      techniques we illustrate approaches to visualizing the saddle set, and confirm
      that the saddle has the Cantor-like fractal structure consistent with a chaotic
      saddle generated by horseshoe-type dynamics.

PMID- 17500987
TI  - Nonrobustness of the two-dimensional turbulent inverse cascade.
AB  - The inverse energy cascade in two-dimensional Navier-Stokes turbulence is
      examined in the quasisteady regime, with small-scale, band-limited forcing at
      scale kf-1, with particular attention to the influence of forcing Reynolds number
      Re on the energy distribution at large scales. The strength of the inverse energy
      cascade, or fraction of energy input that is transferred to larger scales,
      increases monotonically toward unity with increasing Re proportional,
      variantkmax2kf2, where kmax is the maximum resolved wave number. Moreover, as Re
      increases beyond a critical value, for which a direct enstrophy cascade to small
      scales is first realized, the energy spectrum in the energy-cascading range
      steepens from a k-53 to k-2 dependence. The steepening is interpreted as the
      result of a greater tendency for coherent vortex formation in cases when forcing
      scales are adequately resolved. In spectral space, it is associated with
      nonlocality of the inverse energy transfer.

PMID- 17500988
TI  - Thermocapillary valve for droplet production and sorting.
AB  - Droplets are natural candidates for use as microfluidic reactors, if active
      control of their formation and transport can be achieved. We show here that
      localized heating from a laser can block the motion of a water-oil interface,
      acting as a microfluidic valve for two-phase flows. A theoretical model is
      developed to explain the forces acting on a drop due to thermocapillary flow,
      predicting a scaling law that favors miniaturization. Finally, we show how the
      laser forcing can be applied to sorting drops, thus demonstrating how it may be
      integrated in complex droplet microfluidic systems.

PMID- 17500989
TI  - Instability of the perfect subgrid model in implicit-filtering large eddy
      simulation of geostrophic turbulence.
AB  - We demonstrate, in the context of implicit-filtering large eddy simulations
      (LESs) of geostrophic turbulence, that while the attractor of a well-resolved
      statistically stationary turbulent flow can be reached in a coarsely resolved LES
      that is forced by the subgrid scale (SGS) terms diagnosed from the well-resolved
      computation, the attractor is generically unstable: the coarsely resolved LES
      system forced by the diagnosed SGS eddy terms has multiple attractors. This
      points to the importance of interpreting the diagnosed SGS forcing terms in a
      well-resolved computation or experiment from a combined physical-numerical point
      of view rather than from a purely physical point of view.

PMID- 17500990
TI  - Direct observation and theoretical study of cavitation bubbles in liquid mercury.
AB  - The direct observation of cavitation bubbles emerging in liquid mercury under the
      action of mechanical impacts and theoretical investigations on the experimental
      results have been made. Through a glass wall, the image of cavitation bubbles
      appearing near or in contact with the wall was captured by high-speed cameras.
      Discrepancies found between the bubbles' growth rates determined experimentally
      and given by a single-bubble theory have been discussed using a theoretical model
      of Rayleigh-Plesset type that takes into account bubble-bubble and bubble-wall
      interactions. A theoretical equation for the asymptotic growth rate in a
      multibubble case has been given and time dependence of the growth rate under a
      constant negative pressure has been clarified.

PMID- 17500991
TI  - Shear-current effect in a turbulent convection with a large-scale shear.
AB  - The shear-current effect in a nonrotating homogeneous turbulent convection with a
      large-scale constant shear is studied. The large-scale velocity shear causes
      anisotropy of turbulent convection, which produces the mean electromotive force
      epsilon (W) proportional to W x J and the mean electric current along the
      original mean magnetic field, where W is the background mean vorticity due to the
      shear and J is the mean electric current. This results in a large-scale dynamo
      even in a nonrotating and nonhelical homogeneous sheared turbulent convection,
      whereby the alpha effect vanishes. It is found that turbulent convection promotes
      the shear-current dynamo instability, i.e., the heat flux causes positive
      contribution to the shear-current effect. However, there is no dynamo action due
      to the shear-current effect for small hydrodynamic and magnetic Reynolds numbers
      even in a turbulent convection, if the spatial scaling for the turbulent
      correlation time is tau(k) proportionalto to k-2, where k is the small-scale wave
      number.

PMID- 17500992
TI  - Breather generation in fully nonlinear models of a stratified fluid.
AB  - Nonlinear wave motion is studied in a symmetric, continuously stratified,
      smoothed three-layer fluid in the framework of the fully nonlinear Euler
      equations under the Boussinesq approximation. The weakly nonlinear limit is
      discussed in which the governing equations can be reduced to the fully integrable
      modified Korteweg-de Vries equation. For some choices of the layer thicknesses
      the cubic nonlinear term is positive and the modified Korteweg-de Vries equation
      has soliton and breather solutions. Using such a stratification, the Euler
      equations are solved numerically using a sign-variable, initial disturbance.
      Breathers were generated for several forms of the initial disturbance. The
      breathers have moderate amplitude and to a good approximation can be described by
      the modified Korteweg-de Vries equation. As far as we know this is the first
      presentation of a breather in numerical simulations using the full nonlinear
      Euler equations for a stratified fluid.

PMID- 17500993
TI  - Effects of circular rigid boundaries and Coriolis forces on the interfacial
      instability in a rotating annular Hele-Shaw cell.
AB  - We report analytical results for the development of instability of an interface
      between two immiscible, Newtonian fluid layers confined in a rotating annular
      Hele-Shaw cell. We perform a linear stability analysis and focus our study on the
      influence of both Coriolis force and curvature parameters on the interface
      instability growth rate. The results show that the Coriolis force does not alter
      the stability of a disturbance with a particular wave number but reduces the
      maximum growth rate. The results related to the role played by the confinement of
      the liquid layers are also shown to provide a modification of the fastest-growing
      mode and its corresponding linear growth rate.

PMID- 17500994
TI  - Spreading and fingering in spin coating.
AB  - We study the spreading and fingering of drops of silicone oil on a rotating
      substrate for a range of rotation speeds and drop volumes. The spreading of the
      drop prior to the onset of fingering is found to follow the theoretically
      predicted time dependence, but with a large shift in time scale. For the full
      range of experimental parameters studied, the contact line becomes unstable and
      fingers develop when the radius of the drop becomes sufficiently large. We study
      the growth of perturbations around the perimeter of the drop and find the growth
      rate of the most unstable mode to agree well with the predictions of lubrication
      theory. The number of fingers which form around the perimeter of the drop is
      found to be a function of both rotation speed and drop volume, and is also in
      excellent agreement with theoretical predictions.

PMID- 17500995
TI  - Pressure-correlated dispersion of inertial particles in free shear flows.
AB  - We investigate the relationship between dispersion of inertial particles and the
      pressure field in free shear flows. A three-dimensional temporally developing
      particle-laden mixing layer and a three-dimensional spatially developing particle
      laden plane jet are studied by means of direct numerical simulation. The
      incompressible Navier-Stokes equations are accurately solved without any
      turbulence model. The dispersed inertial particles are traced in the Lagrangian
      framework. It is found that the instantaneous spatial distribution of inertial
      particles correlates well with the Laplacian of pressure inverted delta2p , and
      from the statistical viewpoint, the effect of particle size on the fraction of
      particle number distributed within different flow zones characterized by inverted
      delta2p for different particles is negligible when the flow is well developed.
      The potential explanations and applications for this feature are explored.

PMID- 17500996
TI  - Sivashinsky equation in a rectangular domain.
AB  - The (Michelson) Sivashinsky equation of premixed flames is studied in a
      rectangular domain in two dimensions. A huge number of two-dimensional (2D)
      stationary solutions are trivially obtained by the addition of two 1D solutions.
      With Neumann boundary conditions, it is shown numerically that adding two stable
      1D solutions leads to a 2D stable solution. This type of solution is shown to
      play an important role in the dynamics of the equation with additive noise.

PMID- 17500997
TI  - Influence of wettability conditions on slow evaporation in two-dimensional porous
      media.
AB  - We study numerically the influence of the wettability condition on slow
      evaporation in two-dimensional pore square networks of aspect ratio 1. We show
      how evaporation in a hydrophobic network can be simulated numerically by
      combining imbibition rules and the computation of diffusion transport in the gas
      phase. Then we conduct a statistical study of drying in hydrophilic or
      hydrophobic networks based on pore network simulations. We concentrate on the
      situation where the external transfer resistance and liquid film effect are
      negligible and the invasion is dominated by capillary effects. It is found that
      drying in a hydrophilic network is significantly faster than in a hydrophobic
      one. The dimensionless overall drying time is found to be network size dependent,
      approaching exponentially a limit for large size hydrophilic networks. The
      dimensionless average overall drying time is 0.93 and 0.75 in hydrophobic and
      hydrophilic large networks, respectively. Other properties, such as the overall
      saturation and the evaporation flux (through the concept of equivalent flat front
      position) are also studied. In a last part the impact of liquid film flow on the
      overall drying time fluctuation is briefly investigated for the case of
      hydrophilic networks. It is found that the films dampen the drying time
      fluctuations.

PMID- 17500998
TI  - Intermittent nature of solar wind turbulence near the Earth's bow shock: phase
      coherence and non-Gaussianity.
AB  - The link between phase coherence and non-Gaussian statistics is investigated
      using magnetic field data observed in the solar wind turbulence near the Earth's
      bow shock. The phase coherence index Cphi, which characterizes the degree of
      phase correlation (i.e., nonlinear wave-wave interactions) among scales, displays
      a behavior similar to kurtosis and reflects a departure from Gaussianity in the
      probability density functions of magnetic field fluctuations. This demonstrates
      that nonlinear interactions among scales are the origin of intermittency in the
      magnetic field turbulence.

PMID- 17500999
TI  - Approach for simultaneous measurement of two-dimensional angular distribution of
      charged particles. III. Fine focusing of wide-angle beams in multiple lens
      systems.
AB  - This paper provides a way of focusing wide-angle charged-particle beams in
      multiple lens systems. In previous papers [H. Matsuda, Phys. Rev. E 71, 066503
      (2005); 74, 036501 (2006)], it was shown that an ellipsoidal mesh, combined with
      electrostatic lenses, enables correction of spherical aberration over wide
      acceptance angles up to +/-60 degrees . In this paper, practical situations where
      ordinary electron lenses are arranged behind the wide-angle electrostatic lenses
      are taken into account using ray tracing calculation. For practical realization
      of the wide-angle lens systems, the acceptance angle is set to +/-50 degrees . We
      note that the output beams of the wide-angle electrostatic lenses have somewhat
      large divergence angles which cause unacceptable or non-negligible spherical
      aberration in additional lenses. A solution to this problem is presented showing
      that lens combinations to cancel spherical aberration are available, whereby wide
      angle charged-particle beams can be finely focused with considerably reduced
      divergence angles less than +/-5 degrees .

PMID- 17501000
TI  - Ambipolar diffusion in complex plasma.
AB  - A self-consistent model of the ambipolar diffusion of electrons and ions in
      complex (dusty) plasmas accounting for the local electric fields, the dust grain
      charging process, and the interaction of the plasma particles with the dust
      grains and neutrals is presented. The dependence of the diffusion coefficient on
      the interaction of the electrons and ions with the dust grains as well as with
      the neutrals are investigated. It is shown that increase of the dust density
      leads to a reduction of the diffusion scale length, and this effect is enhanced
      at higher electron densities. The dependence of the diffusion scale length on the
      neutral gas pressure is found to be given by a power law, where the absolute
      value of the power exponent decreases with increase of the dust density. The
      electric field gradient and its effects are shown to be significant and should
      thus be taken into account in studies of complex plasmas with not very small dust
      densities. The possibility of observing localized coherent dissipative nonlinear
      dust ion-acoustic structures in an asymmetrically discharged double plasma is
      discussed.

PMID- 17501001
TI  - Band structures of one-dimensional subwavelength photonic crystals containing
      metamaterials.
AB  - We study the band structures of one-dimensional (1D) photonic crystals (PCs) in
      the subwavelength limit. A "spatial-averaged single-negative" (SASN) gap whose
      edges correspond to zero (volume) averaged permittivity (epsilon=0) and zero
      (volume) averaged permeability (micro=0) will appear when metamaterial is
      included in the PC. Unlike the Bragg gap, the frequency range of the SASN gap is
      invariant to the geometrical scaling and insensitive to the incident angle and
      disorder. In the subwavelength limit, both the zero-n gap in the left-handed 1D
      PC and the zero-effective-phase gap in the single-negative 1D PC can be
      understood as SASN gaps. When the subwavelength condition is not fulfilled, the
      zero-n gap and zero-effective-phase gap begin to act differently.

PMID- 17501002
TI  - Localized modes and bistable scattering in nonlinear network junctions.
AB  - We study the properties of junctions created by the crossing of N identical
      branches of linear discrete networks. We reveal that for N>2 such a junction
      creates a topological defect and supports two types of spatially localized modes.
      We analyze the wave scattering by the junction defect and demonstrate nonzero
      reflection for any set of parameters. If the junction is nonlinear, it is
      possible to achieve the maximum transmission for any frequency by tuning the
      intensity of the scattering wave. In addition, near the maximum transmission the
      system shows the bistable behavior.

PMID- 17501003
TI  - Interactions of renormalized waves in thermalized Fermi-Pasta-Ulam chains.
AB  - The dispersive interacting waves in Fermi-Pasta-Ulam (FPU) chains of particles in
      thermal equilibrium are studied from both statistical and wave resonance
      perspectives. It is shown that, even in a strongly nonlinear regime, the chain in
      thermal equilibrium can be effectively described by a system of weakly
      interacting renormalized nonlinear waves that possess (i) the Rayleigh-Jeans
      distribution and (ii) zero correlations between waves, just as noninteracting
      free waves would. This renormalization is achieved through a set of canonical
      transformations. The renormalized linear dispersion of these renormalized waves
      is obtained and shown to be in excellent agreement with numerical experiments.
      Moreover, a dynamical interpretation of the renormalization of the dispersion
      relation is provided via a self-consistency, mean-field argument. It turns out
      that this renormalization arises mainly from the trivial resonant wave
      interactions, i.e., interactions with no momentum exchange. Furthermore, using a
      multiple time-scale, statistical averaging method, we show that the interactions
      of near-resonant waves give rise to the broadening of the resonance peaks in the
      frequency spectrum of renormalized modes. The theoretical prediction for the
      resonance width for the thermalized beta -FPU chain is found to be in very good
      agreement with its numerically measured value.

PMID- 17501004
TI  - Direct perturbation theory for the dark soliton solution to the nonlinear
      Schrodinger equation with normal dispersion.
AB  - After finding the basic solutions of the linearized nonlinear Schrodinger
      equation by the method of separation of variables, the perturbation theory for
      the dark soliton solution is constructed by linear Green's function theory. In
      application to the self-induced Raman scattering, the adiabatic corrections to
      the soliton's parameters are obtained and the remaining correction term is given
      as a pure integral with respect to the continuous spectral parameter.

PMID- 17501005
TI  - Coherence loss in light backscattering by random media with nanoscale
      nonuniformities.
AB  - An experimental technique for measuring time-resolved coherence loss and
      destruction of backscattered wave packets in random media is described. The
      results of such measurements, performed with a modified Michelson interferometer,
      contain rich information about the characteristics of media nonuniformities.
      Experimental data for model nanosuspensions are compared with theoretical
      expressions developed in the paper which include the effects of Mie-type resonant
      scattering. We attribute one such observed effect to enhanced ineleastic optical
      transitions near the surface of nonmetallic nanoparticles. The inverse problem of
      characterization of multiscattering random media by backscattering is also
      considered.

PMID- 17501006
TI  - Acoustic wave transparency for a multilayered sphere with acoustic metamaterials.
AB  - By analogy with the electromagnetic wave, the acoustic transparency phenomenon is
      analyzed for a multilayered sphere with acoustic metamaterials. The neutral
      inclusion concept is used to predict the transparency conditions in the
      quasistatic case, which are further confirmed by a full-wave analysis. The
      mechanism of the transparency is based on lowering the total-scattering cross
      section of the composite sphere. It is found that, to improve the transparency,
      the angle-dependent scattering cross section must also be minimized for all
      directions.

PMID- 17501007
TI  - Dynamics of light propagation in spatiotemporal dielectric structures.
AB  - Propagation, transmission and reflection properties of linearly polarized plane
      waves and arbitrarily short electromagnetic pulses in one-dimensional
      dispersionless dielectric media possessing an arbitrary space-time dependence of
      the refractive index are studied by using a two-component, highly symmetric
      version of Maxwell's equations. The use of any slow varying amplitude
      approximation is avoided. Transfer matrices of sharp nonstationary interfaces are
      calculated explicitly, together with the amplitudes of all secondary waves
      produced in the scattering. Time-varying multilayer structures and spatiotemporal
      lenses in various configurations are investigated analytically and numerically in
      a unified approach. Several effects are reported, such as pulse compression,
      broadening and spectral manipulation of pulses by a spatiotemporal lens, and the
      closure of the forbidden frequency gaps with the subsequent opening of wave
      number band gaps in a generalized Bragg reflector.

PMID- 17501008
TI  - Phenomenological model to fit complex permittivity data of water from radio to
      optical frequencies.
AB  - A general factorized form of the dielectric function together with a fractional
      model-based parameter estimation method is used to provide an accurate analytical
      formula for the complex refractive index in water for the frequency range 10(8)
      10(16)Hz . The analytical formula is derived using a combination of a microscopic
      frequency-dependent rational function for adjusting zeros and poles of the
      dielectric dispersion together with the macroscopic statistical Fermi-Dirac
      distribution to provide a description of both the real and imaginary parts of the
      complex permittivity for water. The Fermi-Dirac distribution allows us to model
      the dramatic reduction in the imaginary part of the permittivity in the visible
      window of the water spectrum.

PMID- 17501009
TI  - Stabilization of high-order solutions of the cubic nonlinear Schrodinger
      equation.
AB  - In this paper we consider the stabilization of nonfundamental unstable stationary
      solutions of the cubic nonlinear Schrodinger equation. Specifically, we study the
      stabilization of radially symmetric solutions with nodes and asymmetric complex
      stationary solutions. For the first ones, we find partial stabilization similar
      to that recently found for vortex solutions while for the later ones
      stabilization does not seem possible.

PMID- 17501010
TI  - Fast algorithm to calculate density of states.
AB  - An algorithm to calculate the density of states, based on the well-known Wang
      Landau method, is introduced. Independent random walks are performed in different
      restricted ranges of energy, and the resultant density of states is modified by a
      function of time, F(t) proportional to t-1, for large time. As a consequence, the
      calculated density of state, gm(E,t) , approaches asymptotically the exact value
      g(ex)(E) as proportional to t-1/2, avoiding the saturation of the error. It is
      also shown that the growth of the interface of the energy histogram belongs to
      the random deposition universality class.

PMID- 17501011
TI  - Top-down extended meshing algorithm and its applications to Green's tensor nano
      optics calculations.
AB  - We present a computational algorithm which speeds up Green's tensor nano-optics
      calculations by means of optimizing the mesh that represents the system we want
      to investigate. The algorithm automates the process of creating a variable-size
      mesh that describes an arbitrary nanostructure. The total number of elements of
      this mesh is smaller than that of a regular mesh representing the same structure,
      and thus the Green's tensor calculations can be performed faster. Precision,
      however, is kept at a similar level than for the regular mesh. Typically, the
      algorithm yields a mesh that speeds up Green's tensor calculations by a factor of
      4, while giving a maximum error in the field magnitude of about 5%. The speed-up
      factor makes it very suitable for otherwise lengthy calculations, and the error
      should be acceptable for most applications.

PMID- 17501012
TI  - Spectral method study of domain coarsening.
AB  - The self-organization of particles in a two phase system in the coexistence
      region through a diffusive mechanism is known as Ostwald ripening. The late stage
      of Ostwald ripening is studied here through the use of a mesoscopic model in
      conjunction with a special configuration that allows for the direct measurement
      of system characteristics such as domain size. The mesoscopic model is a
      stochastic partial integrodifferential equation and is studied through the use of
      recently developed and benchmarked spectral schemes. The size of the growing
      region is not observed to increase as a power law in this model during the late
      stages of self-organization in contrast to the power law growth observed in
      simulations of the earlier stages of self-organization. The results included here
      also demonstrate the effect of adjusting the interparticle interaction on the
      morphological evolution of the system.

PMID- 17501013
TI  - Coupling lattice Boltzmann and molecular dynamics models for dense fluids.
AB  - We propose a hybrid model, coupling lattice Boltzmann (LB) and molecular dynamics
      (MD) models, for the simulation of dense fluids. Time and length scales are
      decoupled by using an iterative Schwarz domain decomposition algorithm. The MD
      and LB formulations communicate via the exchange of velocities and velocity
      gradients at the interface. We validate the present LB-MD model in simulations of
      two- and three-dimensional flows of liquid argon past and through a carbon
      nanotube. Comparisons with existing hybrid algorithms and with reference MD
      solutions demonstrate the validity of the present approach.

PMID- 17501014
TI  - Lattice Boltzmann method for double-diffusive natural convection.
AB  - A lattice Boltzmann method for double-diffusive natural convection is presented.
      The model combines a multicomponent lattice Boltzmann scheme with a finite
      difference solution of the energy equation to simulate natural convection caused
      by gradients in temperature and concentration. The model is validated both in two
      and three dimensions, and the agreement with literature data is satisfactory. A
      case study of thermosolutal convection of air in a cubical enclosure with
      horizontal thermal and solutal gradients is presented, exhibiting a rich variety
      of flow structures.

PMID- 17501015
TI  - Exact and approximative imaging methods for photoacoustic tomography using an
      arbitrary detection surface.
AB  - Two universal reconstruction methods for photoacoustic (also called optoacoustic
      or thermoacoustic) computed tomography are derived, applicable to an arbitrarily
      shaped detection surface. In photoacoustic tomography acoustic pressure waves are
      induced by illuminating a semitransparent sample with pulsed electromagnetic
      radiation and are measured on a detection surface outside the sample. The imaging
      problem consists in reconstructing the initial pressure sources from those
      measurements. The first solution to this problem is based on the time reversal of
      the acoustic pressure field with a second order embedded boundary method. The
      pressure on the arbitrarily shaped detection surface is set to coincide with the
      measured data in reversed temporal order. In the second approach the
      reconstruction problem is solved by calculating the far-field approximation, a
      concept well known in physics, where the generated acoustic wave is approximated
      by an outgoing spherical wave with the reconstruction point as center. Numerical
      simulations are used to compare the proposed universal reconstruction methods
      with existing algorithms.

PMID- 17501016
TI  - Supersymmetric Langevin equation to explore free-energy landscapes.
AB  - The recently discovered supersymmetric generalizations of the Langevin dynamics
      and Kramers equation can be utilized for the exploration of free-energy
      landscapes of systems whose large time-scale separation hampers the usefulness of
      standard molecular dynamics techniques. The first realistic application is here
      presented. The system chosen is a minimalist model for a short alanine peptide
      exhibiting a helix-coil transition.

PMID- 17501017
TI  - Wetting condition in diffuse interface simulations of contact line motion.
AB  - We investigate the wetting condition for diffuse-interface methods in the
      simulation of two-fluid flows with moving contact lines. A current method, which
      uses a surface-energy approach, is shown not to result in a slope of the
      interface that is consistent with the prescribed value of the contact angle. A
      geometric formulation is proposed that does result in the prescribed contact
      angle. Test results are presented for the axisymmetric droplet spreading due to
      the capillary force and the motion of a droplet on a solid substrate in a shear
      flow.

PMID- 17501018
TI  - Using convex quadratic programming to model random media with Gaussian random
      fields.
AB  - Excursion sets of Gaussian random fields (GRFs) have been frequently used in the
      literature to model two-phase random media with measurable phase autocorrelation
      functions. The goal of successful modeling is finding the optimal field
      autocorrelation function that best approximates the prescribed phase
      autocorrelation function. In this paper, we present a technique which uses convex
      quadratic programming to find the best admissible field autocorrelation function
      under a prescribed discretization. Unlike previous methods, this technique
      efficiently optimizes over all admissible field autocorrelation functions,
      instead of optimizing only over a predetermined parametrized family. The results
      from using this technique indicate that the GRF model is significantly more
      versatile than observed in previous studies. An application to modeling a base
      catalyzed tetraethoxysilane aerogel system given small-angle neutron scattering
      data is also presented.

PMID- 17501019
TI  - Explicit analytic formulas for Newtonian Taylor-Couette primary instabilities.
AB  - In this study, existing primary stability boundary data for flow between
      concentric cylinders, for the broad range of radius and rotation ratios examined,
      were found to be self-similar in a properly chosen parameter space. The
      experimental results for the primary transitions to both Taylor vortex flow and
      spiral vortex flow collapsed onto a single curve using a combination of variables
      technique, for both counter-rotating and co-rotating cylinders. The curves were
      then empirically fit, yielding explicit analytic formulas for the critical
      Reynolds number for any radius ratio (eta) and rotation ratio (micro) . For
      counter-rotating flows, the primary critical Reynolds number is determined by a
      single variable: the ratio of the nodal gap fraction to a known function of the
      radius ratio. The existence and influence of a nodal surface is shown
      experimentally for micro approximately equal -1.7. For co-rotating flows, the
      important scaled variable was found to be the radius ratio divided by the nodal
      radius ratio. Comparisons of the resulting explicit stability formulas were made
      to existing analytic stability expressions and experimental data. Excellent
      quantitative agreement was found with data across the entire parameter space.

PMID- 17501020
TI  - Rotational stabilization of pinch instabilities in Taylor-Couette flow.
AB  - The axisymmetric linear stability of dissipative Taylor-Couette flow with an
      azimuthal magnetic field is considered. The magnetic field can be unstable
      without a rotation. This is the well-known pinch type instability. The stable
      rotation stabilizes the unstable azimuthal magnetic field. The dissipative flow
      stability can be classified according to Michael's stability condition for an
      ideal flow. The dissipative effects stabilize the flow and an ideally unstable
      flow becomes really unstable only when both the angular velocity and the magnetic
      field exceed some critical values.

PMID- 17501021
TI  - Inductionless magnetorotational instability in a Taylor-Couette flow with a
      helical magnetic field.
AB  - We consider the magnetorotational instability (MRI) of a hydrodynamically stable
      Taylor-Couette flow with a helical external magnetic field in the inductionless
      approximation defined by a zero magnetic Prandtl number (Pm=0) . This leads to a
      considerable simplification of the problem eventually containing only
      hydrodynamic variables. First, we point out that magnetic field adds more
      dissipation while it does not change the base flow which is the only source of
      energy for growing perturbations. Thus, it seems unclear from the energetic point
      of view how such a hydrodynamically stable flow can turn unstable in the presence
      of a helical magnetic field as it has been found recently by Hollerbach and
      Rudiger [Phys. Rev. Lett. 95, 124501 (2005)]. We revisit this problem by using a
      Chebyshev collocation method to calculate the eigenvalue spectrum of the
      linearized problem. In this way, we confirm that a helical magnetic field can
      indeed destabilize the flow in the inductionless approximation. Second, we
      integrate the linearized equations in time to study the transient behavior of
      small amplitude perturbations, thus showing that the energy arguments are correct
      as well. However, there is no real contradiction between both facts. The linear
      stability theory predicts the asymptotic development of an arbitrary small
      amplitude perturbation, while the energy stability theory yields the instant
      growth rate of any particular perturbation, but it does not account for the
      evolution of this perturbation. Thus, although switching on the magnetic field
      instantly increases the energy decay rate of the dominating hydrodynamic
      perturbation, in the same time this perturbation ceases to be an eigenmode in the
      presence of the magnetic field. Consequently, this perturbation is transformed
      with time and so becomes able to extract energy from the base flow necessary for
      the growth.

PMID- 17501022
TI  - Weierstrass's criterion and compact solitary waves.
AB  - Weierstrass's theory is a standard qualitative tool for single degree of freedom
      equations, used in classical mechanics and in many textbooks. In this Brief
      Report we show how a simple generalization of this tool makes it possible to
      identify some differential equations for which compact and even semicompact
      traveling solitary waves exist. In the framework of continuum mechanics, these
      differential equations correspond to bulk shear waves for a special class of
      constitutive laws.

PMID- 17501023
TI  - Lyapunov instability of rigid diatomic molecules in three dimensions: a simpler
      method.
AB  - We present a method to calculate Lyapunov exponents of rigid diatomic molecules
      in three dimensions ( 12N -dimensional phase space). The spectra of Lyapunov
      exponents are obtained for 32 rigid diatomic molecules interacting through the
      Weeks-Chandler-Anderson potential for various bond length and densities, and
      compared with those of Shin [Phys. Rev. E 64, 041106 (2001)]. Our algorithm is
      easy to implement and total CPU time is relatively inexpensive.

PMID- 17501024
TI  - Comment on "Multiple scattering: the key to unravel the subwavelength world from
      the far-field pattern of a scattered wave".
AB  - Contrary to the main conclusion of Simonetti [Phys. Rev. E 73, 036619 (2006)], we
      maintain that multiple scattering (MS) is not the "key" for subwavelength
      detection. Indeed, even with no MS between subwavelength structures,
      subwavelength detection is still possible. Our statement is numerically
      confirmed. A simple mathematical argument explains this result. From our point of
      view, the incorrect conclusion of Simonetti comes from a misinterpretation of the
      Picard's theorem.

PMID- 17501026
TI  - Alleviation of the Fermion-sign problem by optimization of many-body wave
      functions.
AB  - We present a simple, robust, and highly efficient method for optimizing all
      parameters of many-body wave functions in quantum Monte Carlo calculations,
      applicable to continuum systems and lattice models. Based on a strong zero
      variance principle, diagonalization of the Hamiltonian matrix in the space
      spanned by the wave function and its derivatives determines the optimal
      parameters. It systematically reduces the fixed-node error, as demonstrated by
      the calculation of the binding energy of the small but challenging C(2) molecule
      to the experimental accuracy of 0.02 eV.

PMID- 17501027
TI  - Coherence-enhanced imaging of a degenerate Bose-Einstein gas.
AB  - We present coherence-enhanced imaging, an in situ technique that uses Raman
      superradiance to probe the spatial coherence of an ultracold gas. Applying this
      technique, we identify the coherent portion of an inhomogeneous degenerate (87)Rb
      gas and obtain a spatially resolved measurement of the first-order spatial
      correlation function. We find that the decay of spin gratings is enhanced in high
      density regions of a Bose-Einstein condensate, and ascribe the enhancement to
      collective atom-atom scattering. Further, we directly observe spatial
      inhomogeneities that arise generally in the course of extended-sample
      superradiance.

PMID- 17501028
TI  - Vortex formation by merging of multiple trapped Bose-Einstein condensates.
AB  - We report observations of vortex formation by merging and interfering multiple
      (87)Rb Bose-Einstein condensates (BECs) in a confining potential. In this
      experiment, a single harmonic potential well is partitioned into three sections
      by a barrier, enabling the simultaneous formation of three independent,
      uncorrelated BECs. The BECs may either automatically merge together during their
      growth, or for high-energy barriers, the BECs can be merged together by barrier
      removal after their formation. Either process may instigate vortex formation in
      the resulting BEC, depending on the initially indeterminate relative phases of
      the condensates and the merging rate.

PMID- 17501029
TI  - Birkhoff's theorem, many-body response functions, and the ergodic condition.
AB  - The ergodic hypothesis is viewed as one that is physically measurable through
      scattering by an external probe. Linear response theory is used to derive a
      general ergodic condition on the response functions. It is shown that the same
      condition is also implied by Birkhoff's theorem. This coincidence allows us to
      shed light on the abstract terms of the theorem via classical many-body models.

PMID- 17501030
TI  - Superfluid phase diagrams of trapped Fermi gases with population imbalance.
AB  - We present phase diagrams for population-imbalanced, trapped Fermi superfluids
      near unitarity. In addition to providing quantitative values for the superfluid
      transition temperature, the pairing onset temperature, and the transition line
      (separating the Sarma and phase separation regimes), we study experimental
      signatures of these transitions based on density profiles and density differences
      at the center. Predictions on the BCS side of resonance show unexpected behavior,
      which should be searched for experimentally.

PMID- 17501031
TI  - Interferences in the density of two Bose-Einstein condensates consisting of
      identical or different atoms.
AB  - The density of two initially independent condensates which are allowed to expand
      and overlap can show interferences as a function of time due to interparticle
      interaction. Two situations are separately discussed and compared: (1) all atoms
      are identical and (2) each condensate consists of a different kind of atoms.
      Illustrative examples are presented.

PMID- 17501032
TI  - Can spinor dipolar effects be observed in Bose-Einstein condensates?
AB  - Weak dipolar effects in atomic Bose-Einstein condensates (BECs) have recently
      been predicted to develop spin textures. However, observation of the spin
      textures requires us to decrease the magnetic field down to approximately 10
      microG for spin-1 alkali BECs, so that they are not washed out by the Zeeman
      effect. We present a scheme to observe the magnetic dipole-dipole interaction in
      alkali BECs under a realistic magnetic field of approximately 100 mG. Our scheme
      enables us to extract genuine dipolar effects and should apply also to (52)Cr
      BECs.

PMID- 17501033
TI  - Acoustic attenuation probe for Fermion superfluidity in ultracold-atom gases.
AB  - Dilute gas Bose-Einstein condensates (BEC's), currently used to cool fermionic
      atoms in atom traps, can also probe the superfluidity of these fermions. The
      damping rate of BEC-acoustic excitations (phonon modes), measured in the middle
      of the trap as a function of the phonon momentum, yields an unambiguous signature
      of BCS-like superfluidity, provides a measurement of the superfluid gap
      parameter, and gives an estimate of the size of the Cooper pairs in the BEC-BCS
      crossover regime. We also predict kinks in the momentum dependence of the damping
      rate which can reveal detailed information about the fermion quasiparticle
      dispersion relation.

PMID- 17501034
TI  - Scalable architecture for coherence-preserving qubits.
AB  - We propose scalable architectures for the coherence-preserving qubits introduced
      by Bacon, Brown, and Whaley [Phys. Rev. Lett. 87, 247902 (2001)]. These
      architectures employ extra qubits providing additional degrees of freedom to the
      system. These extra degrees of freedom can be used to counter coupling strength
      errors within the coherence-preserving qubit and combat interactions with
      environmental qubits. Importantly, these architectures provide flexibility in
      qubit arrangement, allowing all physical qubits to be arranged in two spatial
      dimensions.

PMID- 17501035
TI  - Estimating entanglement measures in experiments.
AB  - We present a method to estimate entanglement measures in experiments. We show how
      a lower bound on a generic entanglement measure can be derived from the measured
      expectation values of any finite collection of entanglement witnesses. Hence
      witness measurements are given a quantitative meaning without the need of further
      experimental data. We apply our results to a recent multiphoton experiment [M.
      Bourennane, Phys. Rev. Lett. 92, 087902 (2004)], giving bounds on the
      entanglement of formation and the geometric measure of entanglement in this
      experiment.

PMID- 17501036
TI  - Quantum computational complexity of the N-representability problem: QMA complete.
AB  - We study the computational complexity of the N-representability problem in
      quantum chemistry. We show that this problem is quantum Merlin-Arthur complete,
      which is the quantum generalization of nondeterministic polynomial time complete.
      Our proof uses a simple mapping from spin systems to fermionic systems, as well
      as a convex optimization technique that reduces the problem of finding ground
      states to N representability.

PMID- 17501037
TI  - Ground-state fidelity and bipartite entanglement in the Bose-Hubbard model.
AB  - We analyze the quantum phase transition in the Bose-Hubbard model borrowing two
      tools from quantum-information theory, i.e., the ground-state fidelity and
      entanglement measures. We consider systems at unitary filling comprising up to 50
      sites and show for the first time that a finite-size scaling analysis of these
      quantities provides excellent estimates for the quantum critical point. We
      conclude that fidelity is particularly suited for revealing a quantum phase
      transition and pinning down the critical point thereof, while the success of
      entanglement measures depends on the mechanisms governing the transition.

PMID- 17501038
TI  - Gravitational-wave stochastic background from cosmic strings.
AB  - We consider the stochastic background of gravitational waves produced by a
      network of cosmic strings and assess their accessibility to current and planned
      gravitational wave detectors, as well as to big bang nucleosynthesis (BBN),
      cosmic microwave background (CMB), and pulsar timing constraints. We find that
      current data from interferometric gravitational wave detectors, such as Laser
      Interferometer Gravitational Wave Observatory (LIGO), are sensitive to areas of
      parameter space of cosmic string models complementary to those accessible to
      pulsar, BBN, and CMB bounds. Future more sensitive LIGO runs and interferometers
      such as Advanced LIGO and Laser Interferometer Space Antenna (LISA) will be able
      to explore substantial parts of the parameter space.

PMID- 17501039
TI  - Testing general relativity with atom interferometry.
AB  - The unprecedented precision of atom interferometry will soon lead to laboratory
      tests of general relativity to levels that will rival or exceed those reached by
      astrophysical observations. We propose such an experiment that will initially
      test the equivalence principle to 1 part in 10(15) (300 times better than the
      current limit), and 1 part in 10(17) in the future. It will also probe general
      relativistic effects - such as the nonlinear three-graviton coupling, the gravity
      of an atom's kinetic energy, and the falling of light - to several decimals. In
      contrast with astrophysical observations, laboratory tests can isolate these
      effects via their different functional dependence on experimental variables.

PMID- 17501040
TI  - 21-cm radiation: a new probe of variation in the fine-structure constant.
AB  - We investigate the effect of variation in the value of the fine-structure
      constant (alpha) at high redshifts (recombination > z > 30) on the absorption of
      the cosmic microwave background (CMB) at 21 cm hyperfine transition of the
      neutral atomic hydrogen. We find that the 21 cm signal is very sensitive to the
      variations in alpha and it is so far the only probe of the fine-structure
      constant in this redshift range. A change in the value of alpha by 1% changes the
      mean brightness temperature decrement of the CMB due to 21 cm absorption by >5%
      over the redshift range z < 50. There is an effect of similar magnitude on the
      amplitude of the fluctuations in the brightness temperature. The redshift of
      maximum absorption also changes by approximately 5%.

PMID- 17501041
TI  - Anyonic strings and membranes in anti-de Sitter space and dual Aharonov-Bohm
      effects.
AB  - It is observed that strings in AdS(5) x S(5) and membranes in AdS(7) x S(4)
      exhibit long range phase interactions. Two well separated membranes dragged
      around one another in anti-de Sitter space (AdS) acquire phases of 2 pi/N. The
      same phases are acquired by a well separated F and D string dragged around one
      another. The phases are shown to correspond to both the standard and a novel type
      of Aharonov-Bohm effect in the dual field theory.

PMID- 17501043
TI  - Visible cascade Higgs decays to four photons at hadron colliders.
AB  - The presence of a new singlet scalar particle a can open up new decay channels
      for the Higgs boson, through cascades of the form h --> 2a --> X, possibly making
      discovery through standard model channels impossible. If a is CP odd, its decays
      are particularly sensitive to new physics. Quantum effects from heavy fields can
      naturally make h --> 4 g the dominant decay which is difficult to observe at
      hadron colliders, and is allowed by CERN LEP for m(h) > 82 GeV. However, there
      are usually associated decays, either h --> 2g2gamma or h --> 4gamma, which are
      more promising. The decay h-->4gamma is a clean channel that can discover both a
      and h. At the CERN LHC with 300 fb(-1) of luminosity, a branching ratio of order
      10(-4) is sufficient for discovery for a large range of Higgs boson masses. With
      total luminosity of approximately 8 fb(-1), discovery at the Fermilab Tevatron
      requires more than 5 x 10(-3) in branching ratio.

PMID- 17501045
TI  - Coupled-cluster and configuration-interaction calculations for heavy nuclei.
AB  - We compare coupled-cluster (CC) and configuration-interaction (CI) results for
      (56)Ni obtained in the pf-shell basis, focusing on practical CC approximations
      that can be applied to systems with dozens or hundreds of correlated fermions.
      The weight of the reference state and the strength of correlation effects are
      controlled by the gap between the f(7/2) orbit and the f(5/2), p(3/2), p(1/2)
      orbits. Independent of the gap, the CC method with 1p-1h and 2p-2h clusters and a
      noniterative treatment of 3p-3h clusters is as accurate as the more demanding CI
      approach truncated at the 4p-4h level.

PMID- 17501046
TI  - Nuclear charge radii of neutron-deficient lead isotopes beyond N = 104 midshell
      investigated by in-source laser spectroscopy.
AB  - The shape of exotic even-mass (182-190)Pb isotopes was probed by measurement of
      optical isotope shifts providing mean square charge radii (delta(r(2))). The
      experiment was carried out at the isolde (cern) on-line mass separator, using in
      source laser spectroscopy. Small deviations from the spherical droplet model are
      observed, but when compared to model calculations, those are explained by high
      sensitivity of delta(r(2)) to beyond mean-field correlations and small admixtures
      of intruder configurations in the ground state. The data support the
      predominantly spherical shape of the ground state of the proton-magic Z=82 lead
      isotopes near neutron midshell (N=104).

PMID- 17501047
TI  - Scaling laws for the photoionization cross section of two-electron atoms.
AB  - The cross sections for single-electron photoionization in two-electron atoms show
      fluctuations which decrease in amplitude when approaching the double-ionization
      threshold. Based on semiclassical closed orbit theory, we show that the algebraic
      decay of the fluctuations can be characterized in terms of a threshold law sigma
      proportional to |E|(mu) as E --> 0(-) with exponent mu obtained as a combination
      of stability exponents of the triple-collision singularity. It differs from
      Wannier's exponent dominating double-ionization processes. The details of the
      fluctuations are linked to a set of infinitely unstable classical orbits starting
      and ending in the nonregularizable triple collision. The findings are compared
      with quantum calculations for a model system, namely, collinear helium.

PMID- 17501048
TI  - Antiproton confinement in a Penning-Ioffe trap for antihydrogen.
AB  - Antiprotons (p[over]) remain confined in a Penning trap, in sufficient numbers to
      form antihydrogen (H[over ) atoms via charge exchange, when the radial field of a
      quadrupole Ioffe trap is added. This first demonstration with p[over] suggests
      that quadrupole Ioffe traps can be superimposed upon p[over] and e(+) traps to
      attempt the capture of H[over] atoms as they form, contrary to conclusions of
      previous analyses.

PMID- 17501049
TI  - Coherent optical detection of highly excited Rydberg states using
      electromagnetically induced transparency.
AB  - We demonstrate coherent optical detection of highly excited Rydberg states (up to
      n=124) using electromagnetically induced transparency (EIT), providing a direct
      nondestructive probe of Rydberg energy levels. We show that the EIT spectra allow
      direct optical detection of electric field transients in the gas phase, and we
      extend measurements of the fine structure splitting of the nd series up to n=96.
      Coherent coupling of Rydberg states via EIT could also be used for cross-phase
      modulation and photon entanglement.

PMID- 17501050
TI  - Precise control of molecular dynamics with a femtosecond frequency comb.
AB  - We present a general and highly efficient scheme for performing narrow-band Raman
      transitions between molecular vibrational levels using a coherent train of weak
      pump-dump pairs of shaped ultrashort pulses. The use of weak pulses permits an
      analytic description within the framework of coherent control in the perturbative
      regime, while coherent accumulation of many pulse pairs enables near unity
      transfer efficiency with a high spectral selectivity, thus forming a powerful
      combination of pump-dump control schemes and the precision of the frequency comb.
      Simulations verify the feasibility and robustness of this concept, with the aim
      to form deeply bound, ultracold molecules.

PMID- 17501051
TI  - Resonant channel coupling in electron scattering by pyrazine.
AB  - Detailed investigation of the three low-energy resonances seen in electron
      scattering by the diazabenzene molecule pyrazine reveals that the first two are
      nearly pure single-channel shape resonances, but the third is, as long suspected,
      heavily mixed with core-excited resonances built on low-lying triplet states.
      Such resonant channel coupling is likely to be widespread in pi-ring molecules,
      including the nucleobases of DNA and RNA, where it may form a pathway for
      radiation damage.

PMID- 17501052
TI  - Magnetic enhancement in cobalt-manganese alloy clusters.
AB  - Magnetic moments of Co(N)Mn(M) and Co(N)V(M) clusters (N < or = 60; M < or = N/3)
      are measured in molecular beams using the Stern-Gerlach deflection method.
      Surprisingly, the per atom average moments of Co(N)Mn(M) clusters are found to
      increase with Mn concentration, in contrast to bulk CoMn. The enhancement with Mn
      doping is found to be independent of cluster size and composition in the size
      range studied. Meanwhile, Co(N)V(M) clusters show reduction of average moments
      with increasing V doping, consistent with what is expected in bulk CoV. The
      results are discussed within the virtual bound states model.

PMID- 17501053
TI  - Fidelity of an optical memory based on stimulated photon echoes.
AB  - We investigated the preservation of information encoded into the relative phase
      and amplitudes of optical pulses during storage and retrieval in an optical
      memory based on stimulated photon echo. By interfering photon echoes produced in
      a single-mode Ti:Er:LiNbO(3) waveguide, we found that decoherence in the medium
      translates only as loss and not as degradation of information. We measured a
      visibility for interfering echoes close to 100%. These results may have important
      implications for future long-distance quantum communication protocols.

PMID- 17501054
TI  - Quantum interference of electromagnetic fields from remote quantum memories.
AB  - We observe quantum, Hong-Ou-Mandel, interference of fields produced by two remote
      atomic memories. High-visibility interference is obtained by utilizing the finite
      atomic memory time in four-photon delayed coincidence measurements. Interference
      of fields from remote atomic memories is a crucial element in protocols for
      scalable entanglement distribution.

PMID- 17501055
TI  - Three-dimensional vortex solitons in self-defocusing media.
AB  - We demonstrate that families of vortex solitons are possible in a bidispersive
      three-dimensional nonlinear Schrodinger equation. These solutions can be
      considered as extensions of two-dimensional dark vortex solitons which, along the
      third dimension, remain localized due to the interplay between dispersion and
      nonlinearity. Such vortex solitons can be observed in optical media with normal
      dispersion, normal diffraction, and defocusing nonlinearity.

PMID- 17501042
TI  - Evidence for B(0) --> rho(0)rho(0) decays and implications for the Cabibbo
      Kobayashi-Maskawa angle alpha.
AB  - We search for the decays B(0) --> rho(0)rho(0), B(0) --> rho(0)f(0)(980), and
      B(0) --> f(0)(980)f(0)(980) in a sample of about 384 x 10(6) Upsilon(4S) -->
      BB[over] decays collected with the BABAR detector at the PEP-II asymmetric-energy
      e(+)e(-) collider at Stanford Linear Accelerator Center. We find evidence for
      B(0) --> rho(0)rho(0) with 3.5 sigma significance and measure the branching
      fraction B = (1.07 +/- 0.33 +/- 0.19) x 10(-6) and longitudinal polarization
      fraction f(L) = 0.87 +/- 0.13 +/- 0.04, where the first uncertainty is
      statistical, and the second is systematic. The uncertainty on the Cabibbo
      Kobayashi-Maskawa quark-mixing matrix unitarity angle alpha due to penguin
      contributions in B --> rho rho decays is 18 degrees at the 1 sigma level. We also
      set upper limits on the B(0) --> rho(0)f(0)(980) and B(0) --> f(0)(980)f(0)(980)
      decay rates.

PMID- 17501056
TI  - Nonspecular total internal reflection of spatial solitons at the interface
      between highly birefringent media.
AB  - We investigate total internal reflection of nonlocal spatial optical solitons at
      the interface between two differently oriented regions of a highly birefringent
      nematic liquid crystal. The solitons survive the interaction with an induced
      index mismatch and undergo nonspecular reflection, with an emerging angle
      differing appreciably from the incidence angle.

PMID- 17501057
TI  - Refuting the odd-number limitation of time-delayed feedback control.
AB  - We refute an often invoked theorem which claims that a periodic orbit with an odd
      number of real Floquet multipliers greater than unity can never be stabilized by
      time-delayed feedback control in the form proposed by Pyragas. Using a generic
      normal form, we demonstrate that the unstable periodic orbit generated by a
      subcritical Hopf bifurcation, which has a single real unstable Floquet
      multiplier, can in fact be stabilized. We derive explicit analytical conditions
      for the control matrix in terms of the amplitude and the phase of the feedback
      control gain, and present a numerical example. Our results are of relevance for a
      wide range of systems in physics, chemistry, technology, and life sciences, where
      subcritical Hopf bifurcations occur.

PMID- 17501058
TI  - Corrugated waveguide under scaling investigation.
AB  - Some scaling properties for classical light ray dynamics inside a periodically
      corrugated waveguide are studied by use of a simplified two-dimensional nonlinear
      area-preserving map. It is shown that the phase space is mixed. The chaotic sea
      is characterized using scaling arguments revealing critical exponents connected
      by an analytic relationship. The formalism is widely applicable to systems with
      mixed phase space, and especially in studies of the transition from integrability
      to nonintegrability, including that in classical billiard problems.

PMID- 17501059
TI  - Spout states in the selective withdrawal of immiscible fluids through a nozzle
      suspended above a two-fluid interface.
AB  - In selective withdrawal, fluid is withdrawn through a nozzle suspended above the
      flat interface separating two immiscible, density-separated fluids of viscosities
      nu(upper) and nu(lower) = lambda nu(upper). At low withdrawal rates, the
      interface gently deforms into a hump. At a transition withdrawal rate, a spout of
      the lower fluid becomes entrained with the flow of the upper one into the nozzle.
      When lambda=0.005, the spouts at the transition are very thin with features that
      are over an order of magnitude smaller than any observed in the humps. When
      lambda=20, there is an intricate pattern of hysteresis and a spout appears which
      is qualitatively different from those seen at lower lambda. No corresponding
      qualitative difference is seen in the hump shapes.

PMID- 17501060
TI  - General probabilistic approach to the filtration process.
AB  - We show experimentally that clogging is basically a matter of the probability of
      the presence of particles. We describe this process as a function of the main
      variables of the process, namely, the ratio of particle to mesh hole size, the
      solid fraction, and the number of grains arriving at each mesh hole during one
      test, with the help of a simple model, the predictions of which are in very good
      agreement with our experimental data.

PMID- 17501061
TI  - Ion-kinetic-energy measurements and energy balance in a Z-pinch plasma at
      stagnation.
AB  - The ion-kinetic energy throughout K emission in a stagnating plasma was
      determined from the Doppler contribution to the shapes of optically thin lines. X
      ray spectroscopy with a remarkably high spectral resolution, together with
      simultaneous imaging along the pinch, was employed. Over the emission period, a
      drop of the ion-kinetic energy down to the electron thermal energy was seen.
      Axially resolved time-dependent electron-density measurements and absolute
      intensities of line and continuum allowed for investigating, for the first time,
      each segment of the pinch, the balance between the ion-kinetic energy at the
      stagnating plasma, and the total radiation emitted. Within the experimental
      uncertainties, the ion-kinetic energy is shown to account for the total
      radiation.

PMID- 17501062
TI  - Role of surface elastic relaxations in an O-induced nanopattern on Pt(110)-(1 x
      2).
AB  - Scanning tunneling microscopy shows that a nanopattern forms as the Pt(110)-(1 x
      2) surface is exposed to oxygen at room temperature or above. The nanopattern
      consists of [11[over]0] oriented O-induced stripes assembling into a (11 x 2)
      superstructure at high O coverage. The stripes form because the O adsorption
      energy increases by expanding the Pt lattice along the ridges of the surface as
      compared to the bulk. From interplay with density functional theory calculations,
      we show that the O-induced nanoscale periodicity is caused by short-ranged
      elastic relaxations confined to the surface.

PMID- 17501044
TI  - Observation of exclusive electron-positron production in hadron-hadron
      collisions.
AB  - We present the first observation of exclusive e(+)e(-) production in hadron
      hadron collisions, using pp[over] collision data at (square root) s = 1.96 TeV
      taken by the run II Collider Detector at Fermilab, and corresponding to an
      integrated luminosity of 532 pb(-1). We require the absence of any particle
      signatures in the detector except for an electron and a positron candidate, each
      with transverse energy E(T) > 5 GeV and pseudorapidity |eta| < 2. With these
      criteria, 16 events are observed compared to a background expectation of 1.9+/
      0.3 events. These events are consistent in cross section and properties with the
      QED process pp[over] --> p + e(+)e(-) + p[over] through two-photon exchange. The
      measured cross section is 1.6(-0.3)(+0.5)(stat) +/- 0.3(syst) pb. This agrees
      with the theoretical prediction of 1.71+/-0.01 pb.

PMID- 17501063
TI  - Measurement of the 3D Born-Oppenheimer potential of a proton in a hydrogen-bonded
      system via Deep Inelastic Neutron Scattering: the superprotonic conductor
      Rb(3)H(SO(4))(2).
AB  - We report the first direct measurement of the proton 3-D Born-Oppenheimer
      potential in any material. The proton potential surfaces in the hydrogen-bonded
      superprotonic conductor Rb(3)H(SO(4))(2) are extracted from the momentum
      distribution measured using Deep Inelastic Neutron Scattering (DINS). The
      potential has a single minimum along the bond direction, which accounts for the
      absence of the antiferroelectric transition seen in the deuterated material. The
      measured potential is in qualitative agreement with phenomenological double Morse
      potentials that have been used to describe hydrogen bonds in other systems.

PMID- 17501064
TI  - Oxygen vacancy clustering and electron localization in oxygen-deficient SrTiO(3):
      LDA + U study.
AB  - We find, using a local density approximation +Hubbard U method, that oxygen
      vacancies tend to cluster in a linear way in SrTiO(3), a prototypical perovskite
      oxide, accompanied by strong electron localization at the 3d state of the nearby
      Ti transition metal ion. The vacancy clustering and the associated electron
      localization lead to a profound impact on materials properties, e.g., the
      reduction in free-carrier densities, the appearance of characteristic optical
      spectra, and the decrease in vacancy mobility. The high stability against the
      vacancy migration also suggests the physical reality of the vacancy cluster.

PMID- 17501065
TI  - Minimal model for phase separation under slow cooling.
AB  - Inducing phase separation by a sustained change of temperature often induces
      repeated waves of nucleation. As demonstrated in an accompanying movie, these
      oscillations can easily be demonstrated in the classroom by slowly cooling raw
      spirit (i.e., ethanol) and vegetable oil. In the present communication we suggest
      a minimal theoretical model predicting that they are of thermodynamic origin.
      Their frequency depends on the diffusion constant and ramp rate, and is not
      affected by the overall composition and sample geometry. Our experimental data
      support this model.

PMID- 17501067
TI  - Giant metal compression at liquid-solid (Pb-Si, In-Si) Schottky junctions.
AB  - Using a high-energy x-ray transmission-reflection scheme we have studied the
      density profile of solid-liquid Schottky contacts close to the interface. We
      found a massive disturbance of the electronic system on the liquid metal side at
      different interfaces with pronounced density anomalies on a new length scale. The
      liquid metal at the interface forms a strongly compressed layer followed by a
      density depleted layer. The experimental evidence points to a charge transfer
      phenomenon in the metallic system. Control experiments performed at a metal
      insulator interface confirm this picture.

PMID- 17501066
TI  - Internal mechanical response of a polymer in solution.
AB  - We observed single molecules of fluorescently labeled double-stranded (ds) lambda
      DNA held in an anti-Brownian electrokinetic trap. From the measured density
      fluctuations we extract the density-density response function of the molecule
      over times >4.5 ms and distances >250 nm, i.e., how a perturbation in density in
      one part of the molecule propagates through the rest of the molecule. We find a
      nonmonotonic radial dependence of the relaxation time. In contrast with earlier
      measurements on freely diffusing dsDNA, we observe clear signs of internal
      hydrodynamic interactions.

PMID- 17501068
TI  - Electron induced ortho-meta isomerization of single molecules.
AB  - A scanning tunneling microscope operating at 5 K is used to induce the
      isomerization of single chloronitrobenzene molecules on Cu(111) and verify the
      reaction. The threshold voltage of (227+/-7) mV for this reaction is explained
      based on electron-induced vibrational heating. We propose that the isomerization
      is initiated by simultaneous excitation of two vibrational molecular modes via
      inelastically tunneling electrons. This excitation results in a shift of the
      distribution probability of chlorine and hydrogen positions, which facilitates
      their mutual exchange.

PMID- 17501069
TI  - Pb-Pu superlattices: an example of nanostructured actinide materials.
AB  - Density functional theory applied to Pb-Pu superlattices reveals two competing
      phases separated by a Mott transition between itinerant and localized 5f
      electrons. One phase, corresponding to Pu's bulk alpha phase, exhibits paired up
      Pu planes, thereby broadening the 5f bandwidth. Allowing spin polarization to
      emulate the energetics of electron correlation leads to another phase with larger
      volume, narrow 5f bandwidth, and more uniform local crystal structure, similar to
      bulk fcc Pu.

PMID- 17501070
TI  - Metallic ferromagnetism in the Hubbard model: a rigorous example.
AB  - We present the first rigorous example of the Hubbard model in any dimension which
      exhibits metallic ferromagnetism. The model is a genuine Hubbard model with short
      range hopping and on-site Coulomb repulsion, and has many single-electron bands.
      In the limit where the band gap and the Coulomb repulsion become infinite, we
      prove that the ground states are completely ferromagnetic and at the same time
      conducting.

PMID- 17501071
TI  - Mechanism of electric-pulse-induced resistance switching in manganites.
AB  - We investigate the electric-pulse-induced resistance switching in manganite
      systems. We find a "complementarity" effect where the contact resistance of
      electrodes at opposite ends show variations of opposite sign and is reversible.
      The temperature dependence of the magnitude of the effect reveals a dramatic
      enhancement at a temperature T*, below the metal-insulator transition. We
      qualitatively capture these features with a theoretical model, providing evidence
      for the physical mechanism of the resistance switching. We argue that doping
      control of the electronic state of the oxide at the interfaces is the mechanism
      driving the effect.

PMID- 17501072
TI  - Large positive magnetoresistance of insulating organic crystals in the non-ohmic
      region.
AB  - We report a large positive magnetoresistance ratio in insulating organic crystals
      theta-(ET)(2)CsZn(SCN)(4) at low temperatures at which they exhibit highly
      nonlinear current-voltage characteristics. Despite the nonlinearity, the
      magnetoresistance ratio is independent of the applied voltage. The
      magnetoresistance ratio depends little on the magnetic field direction and is
      described by a simple universal function of mu(B)B/k(B)T, where mu(B) is the Bohr
      magneton. The positive magnetoresistance may be caused by magnetic-field-induced
      parallel alignment of spins of mobile and localized electrons, and a resulting
      blockade of electrical conduction due to the Pauli exclusion principle.

PMID- 17501073
TI  - Changing exchange bias in spin valves with an electric current.
AB  - We show that a high-density electric current, injected from a point contact into
      an exchange-biased spin valve, systematically changes the exchange bias. The bias
      can either increase or decrease depending upon the current direction. This
      observation is not readily explained by the well-known spin-transfer torque
      effect in ferromagnetic metal circuits, but could be evidence for the recently
      predicted current-induced torques in antiferromagnetic metals.

PMID- 17501074
TI  - Unusual conductance of polyyne-based molecular wires.
AB  - We report a full self-consistent ab initio calculation of the current-voltage
      curve and the conductance of thiolate capped polyynes in contact with gold
      electrodes. We find the conductance of polyynes an order of magnitude larger
      compared with other conjugated oligomers. The reason lies in the position of the
      Fermi level deep in the highest occupied molecular orbital related resonance.
      With the conductance weakly dependent on the applied bias and almost independent
      of the length of the molecular chain, polyynes appear as nearly perfect molecular
      wires.

PMID- 17501075
TI  - Novel electric field effects on Landau levels in graphene.
AB  - A new effect in graphene in the presence of crossed uniform electric and magnetic
      fields is predicted. Landau levels are shown to be modified in an unexpected
      fashion by the electric field, leading to a collapse of the spectrum, when the
      value of electric to magnetic field ratio exceeds a certain critical value. Our
      theoretical results, strikingly different from the standard 2D electron gas, are
      explained using a "Lorentz boost," and as an "instability of a relativistic
      quantum field vacuum." It is a remarkable case of emergent relativistic type
      phenomena in nonrelativistic graphene. We also discuss few possible experimental
      consequence.

PMID- 17501076
TI  - Dramatic role of critical current anisotropy on flux avalanches in MgB2 films.
AB  - Anisotropic penetration of magnetic flux in MgB(2) films grown on vicinal
      sapphire substrates is investigated using magneto-optical imaging. Regular
      penetration above 10 K proceeds more easily along the substrate surface steps,
      the anisotropy of the critical current being 6%. At lower temperatures the
      penetration occurs via abrupt dendritic avalanches that preferentially propagate
      perpendicular to the surface steps. This inverse anisotropy in the penetration
      pattern becomes dramatic very close to 10 K where all flux avalanches propagate
      in the strongest pinning direction. The observed behavior is fully explained
      using a thermomagnetic model of the dendritic instability.

PMID- 17501077
TI  - Interaction between superconducting vortices and a Bloch wall in ferrite garnet
      films.
AB  - A theoretical model for how Bloch walls occurring in in-plane magnetized ferrite
      garnet films can serve as efficient magnetic micromanipulators is presented. As
      an example, the walls' interaction with Abrikosov vortices in a superconductor in
      close contact with a garnet film is analyzed within the London approximation. The
      model explains how vortices are attracted to such walls, and excellent
      quantitative agreement is obtained for the resulting peaked flux profile
      determined experimentally in NbSe(2) using high-resolution magneto-optical
      imaging of vortices. In particular, this model, when generalized to include
      charged magnetic walls, explains the counterintuitive attraction observed between
      vortices and a Bloch wall of opposite polarity.

PMID- 17501078
TI  - Hysteretic vortex pinning in superconductor-ferromagnet nanocomposites.
AB  - This Letter reports the observation of hysteresis in the vortex pinning in a
      superconductor-ferromagnetic epitaxial nanocomposite consisting of fcc Gd
      particles incorporated in a Nb matrix. We show that this hysteretic pinning is
      associated with magnetic reversal losses in the Gd particles and is fundamentally
      different in origin to pinning interactions previously observed for ferromagnetic
      particles or other microstructural features.

PMID- 17501079
TI  - Novel superconductivity in metallic SnH(4) under high pressure.
AB  - From first-principles calculations, a high-pressure metallic phase of SnH(4) with
      a novel layered structure intercalated by "H(2)" units is revealed. This
      structure is stable at pressure between 70 and 160 GPa. A remarkable feature of
      this structure is the presence of soft modes in the phonon band structure induced
      by Fermi surface nesting and Kohn anomalies that lead to very strong electron
      phonon coupling. The application of the Allen-Dynes modified McMillan equation
      with the calculated electron-phonon coupling parameter lambda shows that a
      superconducting critical temperature close to 80 K can be achieved at 120 GPa.

PMID- 17501080
TI  - Dipole-induced vortex ratchets in superconducting films with arrays of
      micromagnets.
AB  - We investigate the transport properties of superconducting films with periodic
      arrays of in-plane magnetized micromagnets. Two different magnetic textures are
      studied: a square array of magnetic bars and a close-packed array of triangular
      microrings. As confirmed by magnetic force microscopy imaging, the magnetic state
      of both systems can be adjusted to produce arrays of almost pointlike magnetic
      dipoles. By carrying out transport measurements with ac drive, we observed
      experimentally a recently predicted ratchet effect induced by the interaction
      between superconducting vortices and the magnetic dipoles. Moreover, we find that
      these magnetic textures produce vortex-antivortex patterns, which have a crucial
      role in the transport properties of this hybrid system.

PMID- 17501081
TI  - Spectroscopy of the fractional vortex eigenfrequency in a long Josephson 0-kappa
      junction.
AB  - Fractional Josephson vortices carry a magnetic flux Phi, which is a fraction of
      the magnetic flux quantum Phi(0) approximately 2.07 x 10(-15) Wb. Their
      properties are very different from the properties of the usual integer fluxons.
      In particular, fractional vortices in 0-kappa Josephson junctions are pinned and
      have an oscillation eigenfrequency which is expected to be within the Josephson
      plasma gap. Using microwave spectroscopy, we investigate the dependence of the
      eigenfrequency of a fractional Josephson vortex on its magnetic flux Phi and on
      the bias current. The experimental results are in good agreement with the theory.

PMID- 17501082
TI  - Emergence of Fermi pockets in a new excitonic charge-density-wave melted
      superconductor.
AB  - A superconducting state (T(c) approximately 4.2 K) has very recently been
      observed upon successful doping of the charge-density-wave (CDW) ordered
      triangular lattice TiSe(2), with copper. Using state-of-the-art photoemission
      spectroscopy we identify, for the first time, momentum-space locations of doped
      electrons that form the Fermi sea of the superconductor. With doping, we find
      that kinematic nesting volume increases, whereas coherence of the CDW collective
      order sharply drops. In superconducting doping, as chemical potential rises, we
      observe the emergence of a large density of states in the form of a narrow
      electron pocket near the L point of the Brillouin zone with d-like character. The
      k-space spectral evolution directly demonstrates, for the first time, that the
      CDW order parameter microscopically competes with superconductivity in the same
      band.

PMID- 17501083
TI  - Kosterlitz-Thouless behavior in layered superconductors: the role of the vortex
      core energy.
AB  - In layered superconductors (SC) with small interlayer Josephson coupling vortex
      antivortex phase fluctuations characteristic of quasi two-dimensional (2D)
      Kosterlitz-Thouless behavior are expected to be observable at some energy scale
      T(d). While in the 2D case T(d) is uniquely identified by the KT temperature
      T(KT) where the universal value of the superfluid density is reached, we show
      that in a generic anisotropic 3D system T(d) is controlled by the vortex-core
      energy, and can be significantly larger than the 2D scale T(KT). These results
      are discussed in relation to recent experiments in cuprates, which represent a
      typical experimental realization of layered anisotropic SC.

PMID- 17501084
TI  - Ultrafast nanomagnetic toggle switching of vortex cores.
AB  - We present an ultrafast route for a controlled, toggle switching of magnetic
      vortex cores with ultrashort unipolar magnetic field pulses. The switching
      process is found to be largely insensitive to extrinsic parameters, like sample
      size and shape, and it is faster than any field-driven magnetization reversal
      process previously known from micromagnetic theory. Micromagnetic simulations
      demonstrate that the vortex core reversal is mediated by a rapid sequence of
      vortex-antivortex pair creation and annihilation subprocesses. Specific
      combinations of field-pulse strength and duration are required to obtain a
      controlled vortex core reversal. The operational range of this reversal mechanism
      is summarized in a switching diagram for a 200 nm Permalloy disk.

PMID- 17501085
TI  - Density-functional theory study of half-metallic heterostructures: interstitial
      Mn in Si.
AB  - Using density-functional theory within the generalized gradient approximation, we
      show that Si-based heterostructures with 1/4 layer delta doping of interstitial
      Mn (Mn(int)) are half-metallic. For Mn(int) concentrations of 1/2 or 1 layer, the
      states induced in the band gap of delta-doped heterostructures still display high
      spin polarization, about 85% and 60%, respectively. The proposed heterostructures
      are more stable than previously assumed delta layers of substitutional Mn.
      Contrary to widespread belief, the present study demonstrates that interstitial
      Mn can be utilized to tune the magnetic properties of Si, and thus provides a new
      clue for Si-based spintronics materials.

PMID- 17501086
TI  - Sequential tunneling through molecular spin rings.
AB  - We consider electrical transport through molecules with Heisenberg-coupled spins
      arranged in a ring structure in the presence of an easy-axis anisotropy. The
      molecules are coupled to two metallic leads and a gate. In the charged state of
      the ring, a Zener double-exchange mechanism links transport properties to the
      underlying spin structure. This leads to a remarkable contact-site dependence of
      the current, which for an antiferromagnetic coupling of the spins can lead to a
      total suppression of the zero-bias conductance when the molecule is contacted at
      adjacent sites.

PMID- 17501087
TI  - Asymmetric domain nucleation and unusual magnetization reversal in ultrathin Co
      films with perpendicular anisotropy.
AB  - We report unexpected phenomena during magnetization reversal in ultrathin Co
      films and Co/Pt multilayers with perpendicular anisotropy. Using magneto-optical
      Kerr microscopy and magnetic force microscopy we have observed asymmetrical
      nucleation centers where the reversal begins for one direction of the field only
      and is characterized by an acute asymmetry of domain-wall mobility. We have also
      observed magnetic domains with a continuously varying average magnetization,
      which can be explained in terms of the coexistence of three magnetic phases: up,
      down, and striped.

PMID- 17501088
TI  - Projected-wave-function study of the spin-1/2 Heisenberg model on the Kagome
      lattice.
AB  - We perform a Gutzwiller projected-wave-function study for the spin-1/2 Heisenberg
      model on the Kagome lattice to compare energies of several spin-liquid states.
      The result indicates that a U(1)-Dirac spin-liquid state has the lowest energy.
      Furthermore, even without variational parameters, the energy turns out to be very
      close to that found by exact diagonalization. We show that such a U(1)-Dirac
      state represents a quantum phase whose low-energy physics is governed by four
      flavors of two-component Dirac fermions coupled to a U(1) gauge field. These
      results are discussed in the context of recent experiments on
      ZnCu(3)(OH)(6)Cl(2).

PMID- 17501089
TI  - Microscopic and macroscopic signatures of antiferromagnetic domain walls.
AB  - Magnetotransport measurements on small single crystals of Cr, the elemental
      antiferromagnet, reveal the hysteretic thermodynamics of the domain structure.
      The temperature dependence of the transport coefficients is directly correlated
      with the real-space evolution of the domain configuration as recorded by x-ray
      microprobe imaging, revealing the effect of antiferromagnetic domain walls on
      electron transport. A single antiferromagnetic domain wall interface resistance
      is deduced to be of order 5 x 10(-5) mu Omega cm(2) at a temperature of 100 K.

PMID- 17501090
TI  - Classical spin models and the quantum-stabilizer formalism.
AB  - We relate a large class of classical spin models, including the inhomogeneous
      Ising, Potts, and clock models of q-state spins on arbitrary graphs, to problems
      in quantum physics. More precisely, we show how to express partition functions as
      inner products between certain quantum-stabilizer states and product states. This
      connection allows us to use powerful techniques developed in quantum-information
      theory, such as the stabilizer formalism and classical simulation techniques, to
      gain general insights into these models in a unified way. We recover and
      generalize several symmetries and high-low temperature dualities, and we provide
      an efficient classical evaluation of partition functions for all interaction
      graphs with a bounded tree-width.

PMID- 17501091
TI  - Influence of a single quantum dot state on the characteristics of a microdisk
      laser.
AB  - We report a quantum dot microcavity laser with a cw sub-microW lasing threshold,
      where a significant reduction of the lasing threshold is observed when a single
      quantum dot (QD) state is aligned with a cavity mode. The quality factor exceeds
      15,000 before the system lases. When no QD states are resonant, below threshold
      the cavity mode initially degrades with increasing pump power, after which
      saturation occurs and then the cavity mode recovers. We associate the initial
      cavity mode spoiling with QD state broadening that occurs with increasing pump
      power.

PMID- 17501092
TI  - Photon antibunching from a single quantum-dot-microcavity system in the strong
      coupling regime.
AB  - We observe antibunching in the photons emitted from a strongly coupled single
      quantum dot and pillar microcavity in resonance. When the quantum dot was
      spectrally detuned from the cavity mode, the cavity emission remained
      antibunched, and also anticorrelated from the quantum dot emission. Resonant
      pumping of the selected quantum dot via an excited state enabled these
      observations by eliminating the background emitters that are usually coupled to
      the cavity. This device demonstrates an on-demand single-photon source operating
      in the strong coupling regime, with a Purcell factor of 61+/-7 and quantum
      efficiency of 97%.

PMID- 17501093
TI  - Low relaxation rate in epitaxial vanadium-doped ultrathin iron films.
AB  - The longest relaxation time and sharpest frequency content in ferromagnetic
      precession is determined by the intrinsic (Gilbert) relaxation rate G. For many
      years, pure iron (Fe) has had the lowest known value of G = 57 MHz for all pure
      ferromagnetic metals or binary alloys. We show that an epitaxial iron alloy with
      vanadium (V) possesses values of G which are significantly reduced to 35 +/- 5
      MHz at 27% V. The result can be understood as the role of spin-orbit coupling in
      generating relaxation, reduced through the atomic number Z.

PMID- 17501094
TI  - Migration and proliferation dichotomy in tumor-cell invasion.
AB  - We propose a two-component reaction-transport model for the migration
      proliferation dichotomy in the spreading of tumor cells. By using a continuous
      time random walk (CTRW), we formulate a system of the balance equations for the
      cancer cells of two phenotypes with random switching between cell proliferation
      and migration. The transport process is formulated in terms of the CTRW with an
      arbitrary waiting-time distribution law. Proliferation is modeled by a standard
      logistic growth. We apply hyperbolic scaling and Hamilton-Jacobi formalism to
      determine the overall rate of tumor cell invasion. In particular, we take into
      account both normal diffusion and anomalous transport (subdiffusion) in order to
      show that the standard diffusion approximation for migration leads to
      overestimation of the overall cancer spreading rate.

PMID- 17501095
TI  - Hydrodynamics and rheology of active liquid crystals: a numerical investigation.
AB  - We report numerical studies of the hydrodynamics and rheology of an active liquid
      crystal. We confirm the existence of a transition between a passive and an active
      phase, with spontaneous flow in steady state. We explore how the velocity profile
      changes with activity, and we point out the difference in behavior for flow
      aligning and tumbling materials. We find that an active material can thicken or
      thin under a flow, or even exhibit both behaviors as the forcing changes.

PMID- 17501096
TI  - Comment on "optimization of ground- and excited-state wave functions and van der
      waals clusters".

PMID- 17501098
TI  - Comment on "Field-enhanced diamagnetism in the pseudogap state of the cuprate
      Bi(2)Sr(2)CaCu(2)O(8+delta) superconductor in an intense magnetic field".

PMID- 17501100
TI  - Measurement of energy eigenstates by a slow detector.
AB  - We propose a method for a weak continuous measurement of the energy eigenstates
      of a fast quantum system by means of a slow detector. Such a detector is
      sensitive only to slowly changing variables, e.g., energy, while its backaction
      can be limited solely to decoherence of the eigenstate superpositions. We apply
      this scheme to the problem of detection of quantum jumps between energy
      eigenstates in a harmonic oscillator.

PMID- 17501101
TI  - Correlations in a BEC collision: first-principles quantum dynamics with 150,000
      atoms.
AB  - The quantum dynamics of colliding Bose-Einstein condensates with 150,000 atoms
      are simulated directly from the Hamiltonian using the stochastic positive-P
      method. Two-body correlations between the scattered atoms and their velocity
      distribution are found for experimentally accessible parameters. Hanbury Brown
      Twiss or thermal-like correlations are seen for copropagating atoms, while number
      correlations for counterpropagating atoms are even stronger than thermal
      correlations at short times. The coherent phase grains grow in size as the
      collision progresses with the onset of growth coinciding with the beginning of
      stimulated scattering. The method is versatile and usable for a range of cold
      atom systems.

PMID- 17501102
TI  - Resonantly enhanced tunneling of Bose-Einstein condensates in periodic
      potentials.
AB  - We report on measurements of resonantly enhanced tunneling of Bose-Einstein
      condensates loaded into an optical lattice. By controlling the initial conditions
      of our system we were able to observe resonant tunneling in the ground and the
      first two excited states of the lattice wells. We also investigated the effect of
      the intrinsic nonlinearity of the condensate on the tunneling resonances.

PMID- 17501103
TI  - Secret quantum communication of a reference frame.
AB  - We propose quantum-cryptographic protocols to secretly communicate a reference
      frame--unspeakable information in the sense it cannot be encoded into a string of
      bits. Two distant parties can secretly align their Cartesian axes by exchanging N
      spin-1/2 particles, achieving the optimal accuracy 1/N. A possible eavesdropper
      cannot gain any information without being detected.

PMID- 17501104
TI  - NMR experiment factors numbers with Gauss sums.
AB  - We factor the number 157573 using an NMR implementation of Gauss sums. Although
      the current implementation is classical and scales exponentially, we believe that
      an extension to the quantum regime using entangled states is possible.

PMID- 17501105
TI  - Modeling an adiabatic quantum computer via an exact map to a gas of particles.
AB  - We map adiabatic quantum evolution on the classical Hamiltonian dynamics of a 1D
      gas (Pechukas gas) and simulate the latter numerically. This approach turns out
      to be both insightful and numerically efficient, as seen from our example of a
      CNOT gate simulation. For a general class of Hamiltonians we show that the escape
      probability from the initial state scales no faster than |lambda|gamma, where
      |lambda| is the adiabaticity parameter. The scaling exponent for the escape
      probability is gamma=1/2 for all levels, except the edge (bottom and top) ones,
      where gamma approximately < 1/3. In principle, our method can solve arbitrarily
      large adiabatic quantum Hamiltonians.

PMID- 17501106
TI  - Entanglement screening by nonlinear resonances.
AB  - We show that nonlinear resonances in a classically mixed phase space allow us to
      define generic, strongly entangled multipartite quantum states. The robustness of
      their multipartite entanglement increases with the particle number, i.e., in the
      semiclassical limit, for those classes of diffusive noise which assist the
      quantum-classical transition.

PMID- 17501107
TI  - Cluster simulations of loop models on two-dimensional lattices.
AB  - We develop cluster algorithms for a broad class of loop models on two-dimensional
      lattices, including several standard O(n) loop models at n> or =1. We show that
      our algorithm has little or no critical slowing-down when 1< or =n< or =2. We use
      this algorithm to investigate the honeycomb-lattice O(n) loop model, for which we
      determine several new critical exponents, and a square-lattice O(n) loop model,
      for which we obtain new information on the phase diagram.

PMID- 17501108
TI  - TeV gamma rays from photodisintegration and daughter deexcitation of cosmic-ray
      nuclei.
AB  - It is commonly assumed that high-energy gamma rays are made via either purely
      electromagnetic processes or the hadronic process of pion production, followed by
      decay. We investigate astrophysical contexts where a third process (A*) would
      dominate: namely, the photodisintegration of highly boosted nuclei followed by
      daughter deexcitation. Starburst regions such as Cygnus OB2 appear to be
      promising sites for TeV gamma-ray emission via this mechanism. A unique feature
      of the A* process is a sharp flattening of the energy spectrum below
      approximately 10 TeV/(T/eV) for gamma-ray emission from a thermal region of
      temperature T. The A* mechanism described herein offers an important contribution
      to gamma-ray astronomy in the era of intense observational activity.

PMID- 17501109
TI  - Helically symmetric N-particle solutions in scalar gravity.
AB  - Within a scalar model theory of gravity, where the interaction between particles
      is given by the half-retarded plus half-advanced solution of the scalar wave
      equation, we consider an N-body problem: We investigate configurations of N
      particles which form an equilateral N angle and are in helical motion about their
      common center. We prove that there exists a unique equilibrium configuration and
      compute the equilibrium radius explicitly in a post-Newtonian expansion.

PMID- 17501110
TI  - Dark energy versus modified gravity.
AB  - There is now strong observational evidence that the expansion of the Universe is
      accelerating. The standard explanation invokes an unknown "dark energy"
      component. But such scenarios are faced with serious theoretical problems, which
      has led to increased interest in models where instead general relativity is
      modified in a way that leads to the observed accelerated expansion. The question
      then arises whether the two scenarios can be distinguished. Here we show that
      this may not be so easy, demonstrating explicitly that a generalized dark energy
      model can match the growth rate of the Dvali-Gabadadze-Porrati model and
      reproduce the 3+1 dimensional metric perturbations. Cosmological observations are
      then unable to distinguish the two cases.

PMID- 17501114
TI  - Mechanism of near-threshold production of the eta meson.
AB  - Measurements of the analyzing power for the pp-->pp eta reaction have been
      performed at excess energies of Q=10 and 36 MeV. The determined analyzing power
      is essentially consistent with zero, implying dominance of the s wave at both
      excess energies. The angular dependence of the analyzing power, combined with the
      isospin dependence of the total cross section for the eta meson production in
      nucleon-nucleon collisions, reveal that the excitation of the nucleon to the
      S11(1535) resonance is predominantly due to the exchange of the pi meson between
      the colliding nucleons.

PMID- 17501115
TI  - 12C+12C fusion reactions near the Gamow energy.
AB  - The fusion reactions 12C(12C,alpha)20Ne and 12C(12C,p)23Na have been studied from
      E=2.10 to 4.75 MeV by gamma-ray spectroscopy using a C target with ultralow
      hydrogen contamination. The deduced astrophysical S(E)* factor exhibits new
      resonances at E< or =3.0 MeV, in particular, a strong resonance at E=2.14 MeV,
      which lies at the high-energy tail of the Gamow peak. The resonance increases the
      present nonresonant reaction rate of the alpha channel by a factor of 5 near
      T=8x10(8) K. Because of the resonance structure, extrapolation to the Gamow
      energy EG=1.5 MeV is quite uncertain. An experimental approach based on an
      underground accelerator placed in a salt mine in combination with a high
      efficiency detection setup could provide data over the full EG energy range.

PMID- 17501116
TI  - Coulomb excitation of 68,70Cu: first use of postaccelerated isomeric beams.
AB  - We report on the first low-energy Coulomb excitation measurements with
      radioactive Ipi=6- beams of odd-odd nuclei 68,70Cu. The beams were produced at
      ISOLDE, CERN and were post-accelerated by REX-ISOLDE to 2.83 MeV/nucleon. Gamma
      rays were detected with the MINIBALL spectrometer. The 6- beam was used to study
      the multiplet of states (3-, 4-, 5-, 6-) arising from the pi2p3/2 nu 1g9/2
      configuration. The 4- state of the multiplet was populated via Coulomb excitation
      and the B(E2;6--->4-) value was determined in both nuclei. The results obtained
      illustrate the fragile stability of the Z=28 shell and N=40 subshell closures. A
      comparison with large-scale shell-model calculations using the 56Ni core shows
      the importance of the proton excitations across the Z=28 shell gap to the
      understanding of the nuclear structure in the neutron-rich nuclei with N
      approximately 40.

PMID- 17501117
TI  - Direct XUV probing of attosecond electron recollision.
AB  - We demonstrate that the recolliding electron wave packet, fundamental to many
      strong field phenomena, can be directly imaged with sub-A spatial and attosecond
      temporal resolution using attosecond extreme ultraviolet (XUV) pulses. When the
      recolliding electron revisits the parent ion, it can absorb an XUV photon
      yielding high energy electron and thereby providing a measurement of the electron
      energy at the moment of recollision. The full temporal evolution of the
      recollision wave packet can be reconstructed by measuring the photoelectron
      spectra for different time delays between the driving laser and the attosecond
      XUV probe. The strength of the photoelectron signal can be used to characterize
      the spatial distribution of the electron density in the longitudinal direction.
      Elliptical polarization can be used to characterize the electron probability in
      transversal direction.

PMID- 17501118
TI  - Dynamics of light-field control of molecular dissociation at the few-cycle limit.
AB  - We studied the laser-molecule interaction dynamics that leads to the asymmetric
      D+ ion ejection in the dissociative ionization of D2 molecules observed recently
      in Kling et al. [Science 312, 246 (2006)10.1126/science.1126259]. By changing the
      carrier-envelope phase, we showed that the asymmetry is a consequence of
      manipulating the initial ionization and the rescattering of the electrons within
      one optical cycle of the laser. The result illustrates the feasibility of
      coherent control of reaction dynamics at the attosecond time scale.

PMID- 17501119
TI  - Electron collisions with formic acid monomer and dimer.
AB  - Processes induced by the attachment of slow electrons to formic acid and its
      hydrogen-bonded dimer were studied. The elastic cross section and the cross
      section for the excitation of low quanta of discrete vibrations were found to be
      of a similar magnitude for both targets. A dramatic difference was found in the
      excitation of a vibrational quasicontinuum in the 1-2 eV range with the ejection
      of very slow electrons (E<0.1 eV), which was about 20x more intense in the dimer.
      The association of two formic acid molecules to form a dimer thus dramatically
      increases the power to quasithermalize electrons arriving with energies in the 1
      2 eV energy range. Rapid electron-driven intracluster proton transfer is invoked
      to explain the observation.

PMID- 17501120
TI  - Anisotropic explosions of hydrogen clusters under intense femtosecond laser
      irradiation.
AB  - We report on measurements of ion energy distributions from hydrogen clusters
      irradiated by intense laser pulses of duration 40 and 250 fs. Contrary to the
      predictions of a simple Coulomb explosion model, we observe a pronounced spatial
      anisotropy of the ion energies from these explosions with the highest energy ions
      ejected along the laser polarization direction. The origin of the anisotropy is
      distinct from that previously seen in clusters of high Z atoms such as Ar and Xe.
      Furthermore, a measured increase in H+ ion energy when longer, lower intensity
      pulses are employed suggests that multiple-pass, vacuum heating of the cluster
      electrons is important in the deposition of energy by the laser.

PMID- 17501121
TI  - Universal approach to optimal photon storage in atomic media.
AB  - We present a universal physical picture for describing storage and retrieval of
      photon wave packets in a Lambda-type atomic medium. This physical picture
      encompasses a variety of different approaches to pulse storage ranging from
      adiabatic reduction of the photon group velocity and pulse-propagation control
      via off-resonant Raman fields to photon-echo-based techniques. Furthermore, we
      derive an optimal control strategy for storage and retrieval of a photon wave
      packet of any given shape. All these approaches, when optimized, yield identical
      maximum efficiencies, which only depend on the optical depth of the medium.

PMID- 17501122
TI  - Dual-species matter qubit entangled with light.
AB  - We propose and demonstrate an atomic qubit based on a cold 85Rb-87Rb isotopic
      mixture, entangled with a frequency-encoded optical qubit. The interface of an
      atomic qubit with a single spatial light mode, and the ability to independently
      address the two atomic qubit states, should provide the basic interferometrically
      robust element of a quantum network.

PMID- 17501123
TI  - Modal spectroscopy of optoexcited vibrations of a micron-scale on-chip resonator
      at greater than 1 GHz frequency.
AB  - We analyze experimentally and theoretically >1 GHz optoexcited mechanical
      vibration in an on-chip micron-scaled sphere. Different eigen-mechanical modes
      are excited upon demand by the centrifugal radiation pressure of the optical
      whispering-gallery-mode, enabling an optomechanical modal spectroscopy
      investigation of many vibrational modes. Spectral analysis of the light emitted
      from the device enables deduction of its natural vibrational modes in analogy
      with spectroscopy of a molecule's vibrational levels, and its eccentricity
      perturbation is shown to induce spectral splitting.

PMID- 17501124
TI  - Enhanced harmonic generation from expanding clusters.
AB  - We report controlled enhancement of optical third harmonic generation (THG) from
      hydrodynamically expanding clusters of approximately 6x10(5) noble-gas atoms
      several hundred femtoseconds following ionization and heating by ultrashort pump
      pulses. This resonant enhancement is more pronounced for orthogonal than for
      parallel pump-probe polarizations, a consequence of faster cluster expansion
      along the pump polarization. Simulations show that the nonlinear susceptibility
      chi(3) of the individual clusters and the coherence length of the clustered
      plasma medium are optimized nearly simultaneously as the clusters expand, and
      both contribute to the observed THG enhancement. This dual enhancement mechanism
      may be scalable to relativistic probe intensity and to generation of high-order
      harmonics in the soft-x-ray regime.

PMID- 17501125
TI  - Observation of two-dimensional surface solitons.
AB  - We report the first experimental observation of two-dimensional surface solitons
      at the boundaries (edges or corners) of a finite optically induced photonic
      lattice. Both in-phase and gap nonlinear surface self-trapped states were
      observed under single-site excitation conditions. Our experimental results are in
      good agreement with theoretical predictions.

PMID- 17501111
TI  - Lifetime difference and CP-violating phase in the Bs0 system.
AB  - From an analysis of the decay Bs0-->J/psi phi, we obtain the width difference
      between the light and heavy mass eigenstates DeltaGamma identical with (GammaL
      GammaH)=0.17+/-0.09(stat)+/-0.02(syst) ps-1 and the CP-violating phase phis=
      0.79+/-0.56(stat)(-0.01)(+0.14)(syst). Under the hypothesis of no CP violation
      (phis identical with 0), we obtain 1/Gamma=tau(Bs0)=1.52+/-0.08(stat)(
      0.03)(+0.01)(syst) ps and DeltaGamma=0.12(-0.10)(+0.08)(stat)+/-0.02(syst) ps-1.
      The data sample corresponds to an integrated luminosity of about 1.1 fb-1
      accumulated with the D0 detector at the Fermilab Tevatron collider. This is the
      first direct measurement of the CP-violating mixing phase in the Bs0 system.

PMID- 17501126
TI  - Probe of high-order harmonic generation in a hollow waveguide geometry using
      counterpropagating light.
AB  - We use counterpropagating light to directly observe the coherent buildup of high
      harmonic generation in a hollow waveguide geometry. We measure, for the first
      time, coherence lengths for high photon energies that cannot be phase matched
      using conventional approaches. We also probe the transition through phase
      matching, the ionization level at which different harmonic orders are generated,
      and the change in the coherence length as the driving laser is depleted. These
      results directly prescribe the optimal structures or pulse trains required for
      implementing quasiphase matching.

PMID- 17501112
TI  - Measurement of the Lambda b0 lifetime in Lambda b0-->J/psi Lambda 0 in pp
      collisions at square root s=1.96 TeV.
AB  - We report a measurement of the Lambda b0 lifetime in the exclusive decay Lambda
      b0-->J/psi Lambda 0 in pp collisions at square root s=1.96 TeV using an
      integrated luminosity of 1.0 fb-1 of data collected by the CDF II detector at the
      Fermilab Tevatron. Using fully reconstructed decays, we measure tau(Lambda
      b0)=1.593(-0.078)(+0.083)(stat)+/-0.033(syst) ps. This is the single most precise
      measurement of tau(Lambda b0) and is 3.2sigma higher than the current world
      average.

PMID- 17501127
TI  - Oscillations in rapid fracture.
AB  - Experiments of pure tensile fracture in thin brittle gels reveal a new dynamic
      oscillatory instability whose onset occurs at a critical velocity, VC=0.87CS,
      where CS is the shear wave speed. Until VC, crack dynamics are well described by
      linear elastic fracture mechanics (LEFM). These extreme speeds are obtained by
      suppression of the microbranching instability, which occurs when sample
      thicknesses are made comparable to the minimum microbranch width. The wavelength
      of these sinusoidal oscillations is independent of the sample dimensions, thereby
      suggesting that these macroscopic effects are due to an intrinsic microscopic
      scale that is unrelated to LEFM.

PMID- 17501128
TI  - Oscillatory instability in two-dimensional dynamic fracture.
AB  - The stability of a rapid dynamic crack in a two-dimensional infinite strip is
      studied in the framework of linear elastic fracture mechanics supplemented with a
      modified principle of local symmetry. It is predicted that a single crack becomes
      unstable by a finite wavelength oscillatory mode at a velocity vc,
      0.8cR<vc<0.85cR, where cR is the Rayleigh wave speed. The relevance of this
      theoretical calculation to the oscillatory instability reported in the companion
      experimental Letter is discussed.

PMID- 17501129
TI  - Bubble nucleation and growth anomaly for a hydrophilic microheater attributed to
      metastable nanobubbles.
AB  - Nanobubbles on a hydrophilic surface immersed in water and ethanol are inferred
      from the response of the surface to two consecutive heat pulses with a variable
      separation time. Bubble nucleation occurs at specific positions on the surface
      during the first heat pulse but at lower nucleation temperatures and random
      locations on the second. Nanobubbles are hypothesized to form on collapse of the
      bubble from the first pulse.

PMID- 17501130
TI  - Hydrodynamics beyond Navier-Stokes: exact solution to the lattice Boltzmann
      hierarchy.
AB  - The exact solution to the hierarchy of nonlinear lattice Boltzmann (LB) kinetic
      equations in the stationary planar Couette flow is found at nonvanishing Knudsen
      numbers. A new method of solving LB kinetic equations which combines the method
      of moments with boundary conditions for populations enables us to derive closed
      form solutions for all higher-order moments. A convergence of results suggests
      that the LB hierarchy with larger velocity sets is the novel way to approximate
      kinetic theory.

PMID- 17501113
TI  - Measurement of sigma Lambda b0/sigma B0 x B(Lambda b0-->Lambda c+pi-)/B(B0-->D+pi
      ) in pp collisions at square root s=1.96 TeV.
AB  - We present the first observation of the baryon decay Lambda b0-->Lambda c+pi-
      followed by Lambda c+-->pK-pi+ in 106 pb-1 pp collisions at square root s=1.96
      TeV in the CDF experiment. In order to reduce systematic error, the measured rate
      for Lambda b0 decay is normalized to the kinematically similar meson decay B0-
      >D+pi- followed by D+-->pi+K-pi+. We report the ratio of production cross
      sections (sigma) times the ratio of branching fractions (B) for the momentum
      region integrated above pT>6 GeV/c and pseudorapidity range |eta|<1.3: sigma(pp-
      >Lambda b0X)/sigma(pp-->B0X)xB(Lambda b0-->Lambda c+pi-)/B(B0-->D+pi-)=0.82+/
      0.08(stat)+/-0.11(syst)+/-0.22[B(Lambda c+-->pK-pi+)].

PMID- 17501131
TI  - Quantum-electrodynamical photon splitting in magnetized nonlinear pair plasmas.
AB  - We present for the first time the nonlinear dynamics of quantum electrodynamic
      (QED) photon splitting in a strongly magnetized electron-positron (pair) plasma.
      By using a QED corrected Maxwell equation, we derive a set of equations that
      exhibit nonlinear couplings between electromagnetic (EM) waves due to nonlinear
      plasma currents and QED polarization and magnetization effects. Numerical
      analyses of our coupled nonlinear EM wave equations reveal the possibility of a
      more efficient decay channel, as well as new features of energy exchange among
      the three EM modes that are nonlinearly interacting in magnetized pair plasmas.
      Possible applications of our investigation to astrophysical settings, such as
      magnetars, are pointed out.

PMID- 17501132
TI  - Measurements of energy transport patterns in solid density laser plasma
      interactions at intensities of 5x10(20) W cm-2.
AB  - Kalpha x-ray emission, extreme ultraviolet emission, and plasma imaging
      techniques have been used to diagnose energy transport patterns in copper foils
      ranging in thickness from 5 to 75 microm for intensities up to 5x10(20) W cm-2.
      The Kalpha emission and shadowgrams both indicate a larger divergence angle than
      that reported in the literature at lower intensities [R. Stephens, Phys. Rev. E
      69, 066414 (2004)]. Foils 5 microm thick show triple-humped plasma expansion
      patterns at the back and front surfaces. Hybrid code modeling shows that this can
      be attributed to an increase in the mean energy of the fast electrons emitted at
      large radii, which only have sufficient energy to form a plasma in such thin
      targets.

PMID- 17501133
TI  - Carrier-density-dependent lattice stability in InSb.
AB  - The ultrafast decay of the x-ray diffraction intensity following laser excitation
      of an InSb crystal has been utilized to observe carrier dependent changes in the
      potential energy surface. For the first time, an abrupt carrier dependent onset
      for potential energy surface softening and the appearance of accelerated atomic
      disordering for a very high average carrier density have been observed. Inertial
      dynamics dominate the early stages of crystal disordering for a wide range of
      carrier densities between the onset of crystal softening and the appearance of
      accelerated atomic disordering.

PMID- 17501134
TI  - Scaling and universality in rock fracture.
AB  - We present a detailed statistical analysis of acoustic emission time series from
      laboratory rock fracture obtained from different experiments on different
      materials including acoustic emission controlled triaxial fracture and punch
      through tests. In all considered cases, the waiting time distribution can be
      described by a unique scaling function indicating its universality. This scaling
      function is even indistinguishable from that for earthquakes suggesting its
      general validity for fracture processes independent of time, space, and magnitude
      scales.

PMID- 17501135
TI  - Nanomechanical energy transfer and resonance effects in single-walled carbon
      nanotubes.
AB  - Molecular dynamics simulations are employed to elucidate the important factors in
      mechanical energy transfer between carbon nanotubes. Our calculations show that
      sharp resonance effects allow for near complete and highly efficient energy
      transfer. In addition, the weak coupling between two nanotubes sets the time
      scale for the energy transfer. The simulations provide the mechanistic basis for
      a theoretical description of lattice vibration mediated heat flow in nanoscale
      materials.

PMID- 17501136
TI  - Atomistic underpinnings for orientation selection in alloy dendritic growth.
AB  - In dendritic solidification, growth morphologies often display a pronounced
      sensitivity to small changes in composition. To gain insight into the origins of
      this phenomenon, we undertake an atomistic calculation of the magnitude and
      anisotropy of the crystal-melt interfacial free energy in a model alloy system
      featuring no atomic size mismatch and relatively ideal solution thermodynamics.
      By comparing the results of these calculations with predictions from recent phase
      field calculations, we demonstrate that alloying gives rise to changes in free
      energy anisotropies that are substantial on the scale required to induce changes
      in growth orientations.

PMID- 17501137
TI  - Microscopic interpretation of a pure chemical contribution to the Soret effect.
AB  - In a recent Letter by Kohler [Phys. Rev. Lett. 87, 055901 (2001)], it has been
      shown that the Soret effect or thermal diffusion can be split into three
      different contributions: mass, moment of inertia, and a so-called chemical
      effect, but only the chemical effect gives rise to a composition dependent
      contribution. As it is experimentally difficult to deal with the chemical
      contribution without changing the two others, it has not been studied accurately
      yet. Our Letter presents both equilibrium and nonequilibrium Molecular Dynamics
      in simple Lennard-Jones mixtures. By thoroughly changing the strength of direct
      and cross interaction energies between particles, we show that the composition
      dependence and the change of sign of the Soret coefficient is driven only by the
      nature of interactions between unlike particles and propose a microscopic
      interpretation of the Soret effect.

PMID- 17501138
TI  - Insulating ground state of Sn/Si(111)-(square root 3 x square root 3)R30 degrees.
AB  - The Sn/Si(111)-(square root 3 x square root 3)R30 degrees surface was so far
      believed to be metallic according to the electron counting argument. We show, by
      using tunneling spectroscopy, scanning tunneling microscopy, photoemission, and
      photoelectron diffraction, that below 70 K this surface has a very low density of
      states at the Fermi level and is not appreciably distorted. The experimental
      results are compatible with the insulating Mott-Hubbard ground state predicted by
      LSDA+U calculations [G. Profeta and E. Tosatti, Phys. Rev. Lett. 98, 086401
      (2007)].

PMID- 17501139
TI  - Stabilization of charge ordering in La1/3Sr2/3FeO3-delta by magnetic exchange.
AB  - The magnetic exchange energies in charge ordered La1/3Sr2/3FeO3-delta (LSFO) and
      its parent compound LaFeO3 (LFO) have been determined by inelastic neutron
      scattering. In LSFO, the measured ratio of ferromagnetic exchange between Fe3+
      Fe5+ pairs (JF) and antiferromagnetic exchange between Fe3+-Fe3+ pairs (JAF)
      fulfills the criterion for charge ordering driven by magnetic interactions
      (|JF/JAF|>1). The 30% reduction of JAF as compared to LFO indicates that doped
      holes are delocalized, and charge ordering occurs without a dominant influence
      from Coulomb interactions.

PMID- 17501140
TI  - Ferrimagnetism in EuFe4Sb12 due to the interplay of f-electron moments and a
      nearly ferromagnetic host.
AB  - We combine x-ray magnetic circular dichroism spectroscopy at Fe L2,3 edges, at Eu
      M4,5 edges, x-ray absorption spectroscopy (XAS) investigation of Eu valence, and
      local spin density calculations, to show that the filled skutterudite
      Eu0.95Fe4Sb12 is a ferrimagnet in which the Fe 3d moment and the Eu2+ 4f moment
      are magnetically ordered with dominant antiferromagnetic coupling. From Eu L3
      edge XAS, we find that about 13% of the Eu have a formal valence of 3+. We
      ascribe the origin of ferrimagnetism at a relatively high transition temperature
      TC of 85 K in Eu0.95Fe4Sb12 to f-electron interaction with the nearly
      ferromagnetic [Fe4Sb12]2.2- host lattice.

PMID- 17501141
TI  - Transition from a one-dimensional to a quasi-one-dimensional state in interacting
      quantum wires.
AB  - Upon increasing the electron density in a quantum wire, the one-dimensional
      electron system undergoes a transition to a quasi-one-dimensional state. In the
      absence of interactions between electrons, this corresponds to filling up the
      second subband of transverse quantization, and there are two gapless excitation
      modes above the transition. On the other hand, strongly interacting one
      dimensional electrons form a Wigner crystal, and the transition corresponds to it
      splitting into two chains (zigzag crystal). We show that the soft mode driving
      the transition to the zigzag state is gapped, and only one gapless mode exists
      above the transition. Furthermore, we establish that in the vicinity of the
      transition already arbitrarily weak interactions open a gap in the second mode.
      We then argue that only one gapless mode exists near the transition at any
      interaction strength.

PMID- 17501142
TI  - Room-temperature polariton lasing in semiconductor microcavities.
AB  - We observe a room-temperature low-threshold transition to a coherent polariton
      state in bulk GaN microcavities in the strong-coupling regime. Nonresonant pulsed
      optical pumping produces rapid thermalization and yields a clear emission
      threshold of 1 mW, corresponding to an absorbed energy density of 29 microJ cm-2,
      1 order of magnitude smaller than the best optically pumped (In,Ga)N quantum-well
      surface-emitting lasers (VCSELs). Angular and spectrally resolved luminescence
      show that the polariton emission is beamed in the normal direction with an
      angular width of +/-5 degrees and spatial size around 5 microm.

PMID- 17501143
TI  - Superconductivity and magnetic order in CeRhIn5: spectra of coexistence.
AB  - We discuss the fixed-point Hamiltonian and the spectrum of excitations of a quasi
      bidimensional electronic system supporting simultaneously antiferromagnetic
      ordering and superconductivity. The coexistence of these two order parameters in
      a single phase is possible because the magnetic order is linked to the formation
      of a metallic spin density wave, and its order parameter is not associated to a
      spectral gap but to an energy shift of the paramagnetic bands. This peculiarity
      entails several distinct features in the phase diagram and the spectral
      properties of the model, which may have been observed in CeRhIn5. Apart from the
      coexistence, we find an abrupt suppression of the spin density wave when the
      superconducting and magnetic ordering temperatures are equal. The divergence of
      the cyclotron mass extracted from de Haas-van Alphen experiments is also analyzed
      in the same framework.

PMID- 17501144
TI  - Nematic domains and resistivity in an itinerant metamagnet coupled to a lattice.
AB  - The nature of the emergent phase near a putative quantum critical point in the
      bilayer ruthenate Sr3Ru2O7 has been a recent subject of intensive research. It
      has been suggested that this phase may possess electronic nematic order (ENO). In
      this work, we investigate the possibility of nematic domain formation in the
      emergent phase, using a phenomenological model of electrons with ENO and its
      coupling to lattice degrees of freedom. The resistivity due to the scattering off
      the domain walls is shown to closely follow the ENO parameter. Our results
      provide qualitative explanations for the dependence of the resistivity on
      external magnetic fields in Sr3Ru2O7.

PMID- 17501145
TI  - Spin-orbit-induced spin-density wave in a quantum wire.
AB  - We present analysis of the interacting quantum wire problem in the presence of
      magnetic field and spin-orbit interaction. We show that an interesting interplay
      of Zeeman and spin-orbit terms, facilitated by the electron-electron interaction,
      results in the spin-density wave state when the magnetic field and spin-orbit
      axes are orthogonal. This strongly affects charge transport through the wire:
      With the spin-density wave stabilized, single-particle backscattering off a
      nonmagnetic impurity becomes irrelevant. The sensitivity of the effect to the
      direction of the magnetic field can be used for experimental verification of this
      proposal.

PMID- 17501146
TI  - Experimental signature of phonon-mediated spin relaxation in a two-electron
      quantum dot.
AB  - We observe an experimental signature of the role of phonons in spin relaxation
      between triplet and singlet states in a two-electron quantum dot. Using both the
      external magnetic field and the electrostatic confinement potential, we change
      the singlet-triplet energy splitting from 1.3 meV to zero and observe that the
      spin relaxation time depends nonmonotonously on the energy splitting. A simple
      theoretical model is derived to capture the underlying physical mechanism. The
      present experiment confirms that spin-flip energy is dissipated in the phonon
      bath.

PMID- 17501147
TI  - Impurities in a biased graphene bilayer.
AB  - We study the problem of impurities and midgap states in a biased graphene
      bilayer. We show that the properties of the bound states, such as localization
      lengths and binding energies, can be controlled externally by an electric field
      effect. Moreover, the band gap is renormalized and impurity bands are created at
      finite impurity concentrations. Using the coherent potential approximation, we
      calculate the electronic density of states and its dependence on the applied bias
      voltage.

PMID- 17501148
TI  - Very high frequency spectroscopy and tuning of a single-cooper-pair transistor
      with an on-chip generator.
AB  - A single-Cooper-pair transistor (SCPT) is coupled capacitively to a voltage
      biased Josephson junction, used as a high-frequency generator. Thanks to the high
      energy of photons generated by the Josephson junction, transitions between energy
      levels, not limited to the first two levels, were induced and the effect of this
      irradiation on the dc Josephson current of the SCPT was measured. The phase and
      gate bias dependence of energy levels of the SCPT at high energy is probed.
      Because the energies of photons can be higher than the superconducting gap we can
      induce not only transfer of Cooper pairs but also transfer of quasiparticles
      through the island of the SCPT, thus controlling the poisoning of the SCPT. This
      can both decrease and increase the average Josephson energy of the SCPT: its
      supercurrent is then controlled by high-frequency irradiation.

PMID- 17501149
TI  - Stabilized parametric cooper-pair pumping in a linear array of coupled Josephson
      junctions.
AB  - We present an experimentally realizable stabilized charge pumping scheme in a
      linear array of Cooper-pair boxes. The system design intrinsically protects the
      pumping mechanism from severe errors, especially current reversal and spontaneous
      charge excitation. The quantum Zeno effect is implemented to further diminish
      pumping errors. The characteristics of this scheme are considered from the
      perspective of improving the current standard. Such an improvement bears
      relevance to the closure of the so-called measurement triangle (see [D. Averin,
      Nature (London) 434, 285 (2005)).

PMID- 17501150
TI  - Enhancement of the supercurrent at a finite voltage in a sandwich-type ballistic
      SINIS junction.
AB  - A large, reentrant, Josephson current is observed in SINIS
      (Nb/Al/AlOx/Al/AlOx/Al/Nb) junctions at a finite voltage close to Delta/e (where
      Delta is the superconducting energy gap in S) and a bias current exceeding the
      zero-voltage Josephson current. The effect is studied using a multiterminal
      device configuration. A theoretical interpretation in terms of quantized electron
      states in the N layer is provided.

PMID- 17501151
TI  - Quantum metallicity on the high-field side of the superconductor-insulator
      transition.
AB  - We investigate ultrathin superconducting TiN films, which are very close to the
      localization threshold. Perpendicular magnetic field drives the films from the
      superconducting to an insulating state, with very high resistance. Further
      increase of the magnetic field leads to an exponential decay of the resistance
      towards a finite value. In the limit of low temperatures, the saturation value
      can be very accurately extrapolated to the universal quantum resistance h/e2. Our
      analysis suggests that at high magnetic fields a new ground state, distinct from
      the normal metallic state occurring above the superconducting transition
      temperature, is formed. A comparison with other studies on different materials
      indicates that the quantum metallic phase following the magnetic-field-induced
      insulating phase is a generic property of systems close to the disorder-driven
      superconductor-insulator transition.

PMID- 17501152
TI  - Double criticality of the Sherrington-Kirkpatrick model at T=0.
AB  - Numerical results up to the 42nd order of replica-symmetry breaking (RSB) are
      used to predict the singular structure of the Sherrington-Kirkpatrick spin glass
      at T=0. We confirm predominant single parameter scaling and derive corrections
      for the T=0 order function q(a), related to a Langevin equation with pseudotime
      1/a. a=0 and a=infinity are shown to be two critical points for infinity-RSB,
      associated with two discrete spectra of Parisi block size ratios, attached to a
      continuous spectrum. Finite-RSB-size scaling, associated exponents, and T=0
      energy are obtained with unprecedented accuracy.

PMID- 17501153
TI  - Competing ferromagnetic and charge-ordered states in models for manganites: the
      origin of the colossal magnetoresistance effect.
AB  - The one-orbital model for manganites with cooperative phonons and superexchange
      coupling JAF is investigated via large-scale Monte Carlo simulations. The results
      for two orbitals are also briefly discussed. Focusing on the electron density
      n=0.75, a regime of competition between ferromagnetic metallic and charge-ordered
      (CO) insulating states is identified. In the vicinity of the associated
      bicritical point, colossal magnetoresistance (CMR) effects are observed. The CMR
      is associated with the development of short-distance correlations among polarons,
      above the spin ordering temperatures, resembling the charge arrangement of the
      low-temperature CO state.

PMID- 17501154
TI  - Orbital ordering and magnetic field effect in MnV2O4.
AB  - We studied the structural properties of an orbital-spin-coupled spinel oxide,
      MnV2O4, mainly by single-crystal x-ray diffraction measurement. It was found that
      a structural phase transition from cubic to tetragonal and ferrimagnetic ordering
      occur at the same temperature (Ts,TN=57 K). The structural phase transition was
      induced also by magnetic field above Ts. In addition, magnetic-field-induced
      alignment of tetragonal domains results in large magnetostriction below Ts. We
      also found that the structural phase transition is caused by the antiferro-type
      ordering of the V t2g orbitals.

PMID- 17501155
TI  - Magnetic resonance studies of the fundamental spin-wave modes in individual
      submicron Cu/NiFe/Cu perpendicularly magnetized disks.
AB  - Spin-wave spectra of perpendicularly magnetized disks consisting of a 100 nm
      permalloy layer sandwiched between two Cu layers of 30 nm are measured
      individually by a magnetic resonance force microscope. Using 3D micromagnetic
      simulations, it is demonstrated that, for submicron-size diameters, the lowest
      energy spin-wave mode of the saturated state is not spatially uniform, but rather
      is localized at the center of the Py/Cu interfaces in the region of the minimum
      demagnetizing field.

PMID- 17501156
TI  - Translations and rotations are correlated in granular gases.
AB  - In a granular gas of rough particles the axis of rotation is shown to be
      correlated with the translational velocity of the particles. The average relative
      orientation of angular and linear velocities depends on the parameters which
      characterize the dissipative nature of the collision. We derive a simple theory
      for these correlations and validate it with numerical simulations for a wide
      range of coefficients of normal and tangential restitution. The limit of smooth
      spheres is shown to be singular: even an arbitrarily small roughness of the
      particles gives rise to orientational correlations.

PMID- 17501157
TI  - Role of conformational entropy in force-induced biopolymer unfolding.
AB  - A statistical mechanical description of flexible and semiflexible polymer chains
      in a poor solvent is developed in the constant force and constant distance
      ensembles. We predict the existence of many intermediate states at low
      temperatures stabilized by the force. A unified response to pulling and
      compressing forces has been obtained in the constant distance ensemble. We show
      the signature of a crossover length which increases linearly with the chain
      length. Below this crossover length, the critical force of unfolding decreases
      with temperature, while above, it increases with temperature. For stiff chains,
      we report for the first time sawtoothlike behavior in the force-extension curves
      which has been seen earlier in the case of protein unfolding.

PMID- 17501158
TI  - Systematic field theory of the RNA glass transition.
AB  - We prove that the Lassig-Wiese (LW) field theory for the freezing transition of
      the secondary structure of random RNA is renormalizable to all orders in
      perturbation theory. The proof relies on a formulation of the model in terms of
      random walks and on the use of the multilocal operator product expansion.
      Renormalizability allows us to work in the simpler scheme of open polymers, and
      to obtain the critical exponents at 2-loop order. It also allows us to prove some
      exact exponent identities, conjectured by LW.

PMID- 17501159
TI  - Swinging and tumbling of fluid vesicles in shear flow.
AB  - The dynamics of fluid vesicles in simple shear flow is studied using mesoscale
      simulations of dynamically triangulated surfaces, as well as a theoretical
      approach based on two variables: a shape parameter and the inclination angle,
      which has no adjustable parameters. We show that, between the well-known tank
      treading and tumbling states, a new "swinging" state can appear. We predict the
      dynamic phase diagram as a function of the shear rate, the viscosities of the
      membrane and the internal fluid, and the reduced vesicle volume. Our results
      agree well with recent experiments.

PMID- 17501160
TI  - Conformational temperature characterizing the folding of a protein.
AB  - The time sequences of the molecular dynamics simulation for the folding process
      of a protein is analyzed with the inherent structure landscape which focuses on
      the configurational dynamics of the system. Time-dependent energy and entropy for
      inherent structures are introduced, and from these quantities a conformational
      temperature is defined. The conformational temperature follows the time evolution
      of a slow relaxation process and reaches the bath temperature when the system is
      equilibrated. We show that the nonequilibrium system is described by two
      temperatures, one for fast vibration and the other for slow configurational
      relaxation, while the equilibrium system is described by one temperature. The
      proposed formalism is applicable widely for systems with many metastable states.

PMID- 17501161
TI  - Exploring the mechanism of flexible biomolecular recognition with single molecule
      dynamics.
AB  - Combining a single-molecule study of protein binding with a coarse grained
      molecular dynamics model including solvent (water molecules) effects, we find
      that biomolecular recognition is determined by flexibilities in addition to
      structures. Our single-molecule study shows that binding of CBD (a fragment of
      Wiskott-Aldrich syndrome protein) to Cdc42 involves bound and loosely bound
      states, which can be quantitatively explained in our model as a result of binding
      with large conformational changes. Our model identified certain key residues for
      binding consistent with mutational experiments. Our study reveals the role of
      flexibility and a new scenario of dimeric binding between the monomers: first
      bind and then fold.

PMID- 17501162
TI  - Dynamical origin of independent spiking and bursting activity in neural
      microcircuits.
AB  - The relationship between spiking and bursting dynamics is a key question in
      neuroscience, particularly in understanding the origins of different neural
      coding strategies and the mechanisms of motor command generation and neural
      circuit coordination. Experiments indicate that spiking and bursting dynamics can
      be independent. We hypothesize that different mechanisms for spike and burst
      generation, intrinsic neuron dynamics for spiking and a modulational network
      instability for bursting, are the origin of this independence. We tested the
      hypothesis in a detailed dynamical analysis of a minimal inhibitory neural
      microcircuit (motif) of three reciprocally connected Hodgkin-Huxley neurons. We
      reduced this high-dimensional dynamical system to a rate model and showed that
      both systems have identical bifurcations from tonic spiking to burst generation,
      which, therefore, does not depend on the details of spiking activity.

PMID- 17501163
TI  - Anomalous polymer sedimentation far from equilibrium.
AB  - A single flexible polymer in strong sedimentation fields is investigated using
      hydrodynamic simulations and scaling arguments. For short chains and small fields
      compaction is observed. For elevated fields or long chains the chain stretches
      and the sedimentation coefficient decreases, in agreement with ultracentrifuge
      experiments on linear as well as circular DNA. For very large fields a tadpole
      forms consisting of a compact leading head and a trailing stretched tail.

PMID- 17501164
TI  - Chain conformations and bound-layer correlations in polymer nanocomposites.
AB  - Small angle neutron scattering studies on polystyrene loaded with spherical
      silica nanoparticles under contrast-matched conditions unequivocally show that
      chain conformations follow unperturbed Gaussian statistics independent of chain
      molecular weight and filler composition. Liquid state theory calculations are
      consistent with this conclusion and also predict filler-induced modification of
      interchain polymer correlations which have a distinctive scattering signature
      that is in nearly quantitative agreement with our observations.

PMID- 17501165
TI  - Confined space and effective interactions of multiple self-avoiding chains.
AB  - We study the link between three seeming-disparate cases of self-avoiding
      polymers: strongly overlapping multiple chains in dilute solution, chains under
      spherical confinement, and the onset of semidilute solutions. Our main result is
      that the free energy for overlapping n chains is independent of chain length and
      scales as n9/4, slowly crossing over to n3, as n increases. For strongly confined
      polymers inside a spherical cavity, we show that rearranging the chains does not
      cost an additional free energy. Our results imply that, during cell cycle, global
      reorganization of eukaryotic chromosomes in a large cell nucleus could be readily
      achieved.

PMID- 17501166
TI  - Comment on "Jamming percolation and glass transitions in lattice models".

PMID- 17501168
TI  - Decoherence and thermalization.
AB  - We present a rigorous analysis of the phenomenon of decoherence for general N
      level systems coupled to reservoirs of free massless bosonic fields. We apply our
      general results to the specific case of the qubit. Our approach does not involve
      master equation approximations and applies to a wide variety of systems which are
      not explicitly solvable.

PMID- 17501169
TI  - Many-body interband tunneling as a witness of complex dynamics in the Bose
      Hubbard model.
AB  - A perturbative model is studied for the tunneling of many-particle states from
      the ground band to the first excited energy band, mimicking Landau-Zener decay
      for ultracold, spinless atoms in quasi-one-dimensional optical lattices subjected
      to a tunable tilting force. The distributions of the computed tunneling rates
      provide an independent and experimentally accessible signature of the regular
      chaotic transition in the strongly correlated many-body dynamics of the ground
      band.

PMID- 17501170
TI  - Mixtures of Bose gases under rotation.
AB  - We examine the rotational properties of a mixture of two Bose gases. Considering
      the limit of weak interactions between the atoms, we investigate the behavior of
      the system under a fixed angular momentum. We demonstrate a number of exact
      results in this many-body system.

PMID- 17501171
TI  - Ultracold atoms in a disordered crystal of light: towards a bose glass.
AB  - We use a bichromatic optical lattice to experimentally realize a disordered
      system of ultracold strongly interacting 87Rb bosons. In the absence of disorder,
      the atoms are pinned by repulsive interactions in the sites of an ideal optical
      crystal, forming one-dimensional Mott-insulator states. We measure the excitation
      spectrum of the system as a function of disorder strength and characterize its
      phase-coherence properties with a time-of-flight technique. Increasing disorder,
      we observe a broadening of the Mott-insulator resonances and the transition to a
      state with vanishing long-range phase coherence and a flat density of
      excitations, which suggest the formation of a Bose-glass phase.

PMID- 17501172
TI  - Noninvariance of space- and time-scale ranges under a Lorentz Transformation and
      the implications for the study of relativistic interactions.
AB  - We present an analysis which shows that the ranges of space and time scales
      spanned by a system are not invariant under Lorentz transformation. This implies
      the existence of a frame of reference which minimizes an aggregate measure of the
      range of space and time scales. Such a frame is derived, for example, for the
      following cases: free electron laser, laser-plasma accelerator, and particle
      beams interacting with electron clouds. The implications for experimental,
      theoretical, and numerical studies are discussed. The most immediate relevance is
      the reduction by orders of magnitude in computer simulation run times for such
      systems.

PMID- 17501173
TI  - Quantum capacities of bosonic channels.
AB  - We investigate the capacity of bosonic quantum channels for the transmission of
      quantum information. We calculate the quantum capacity for a class of Gaussian
      channels, including channels describing optical fibers with photon losses, by
      proving that Gaussian encodings are optimal. For arbitrary channels we show that
      achievable rates can be determined from few measurable parameters by proving that
      every channel can asymptotically simulate a Gaussian channel which is
      characterized by second moments of the initial channel. Along the way we provide
      a complete characterization of degradable Gaussian channels and those arising
      from teleportation protocols.

PMID- 17501174
TI  - Generic entanglement can be generated efficiently.
AB  - We find that generic entanglement is physical, in the sense that it can be
      generated in polynomial time from two-qubit gates picked at random. We prove as
      the main result that such a process generates the average entanglement of the
      uniform (unitarily invariant) measure in at most O(N3) steps for N qubits. This
      is despite an exponentially growing number of such gates being necessary for
      generating that measure fully on the state space. Numerics furthermore show a
      variation cutoff allowing one to associate a specific time with the achievement
      of the uniform measure entanglement distribution. Various extensions of this work
      are discussed. The results are relevant to entanglement theory and to protocols
      that assume generic entanglement can be achieved efficiently.

PMID- 17501175
TI  - Steady-state conduction in self-similar billiards.
AB  - The self-similar Lorentz billiard channel is a spatially extended deterministic
      dynamical system which consists of an infinite one-dimensional sequence of cells
      whose sizes increase monotonically according to their indices. This special
      geometry induces a nonequilibrium stationary state with particles flowing
      steadily from the small to the large scales. The corresponding invariant measure
      has fractal properties reflected by the phase-space contraction rate of the
      dynamics restricted to a single cell with appropriate boundary conditions. In the
      near-equilibrium limit, we find numerical agreement between this quantity and the
      entropy production rate as specified by thermodynamics.

PMID- 17501176
TI  - Collective working regimes for coupled heat engines.
AB  - Arrays of coupled heat engines are proposed as a paradigmatic model to study the
      trade-off between individual and collective behavior in linear irreversible
      thermodynamics. The analysis reveals the existence of a control parameter which
      selects different operation regimes of the whole array. In particular, the
      regimes of maximum efficiency and maximum power are considered, giving for the
      latter a general derivation of the Curzon-Ahlborn efficiency which surprisingly
      does not depend on whether or not the individual engines in the array work at
      maximum power.

PMID- 17501177
TI  - Critical phenomena in head-on collisions of neutron stars.
AB  - We find type I critical collapses of compact objects modeled by a polytropic
      equation of state (EOS) with a polytropic index Gamma=2 without the
      ultrarelativistic assumption. The object is formed in head-on collisions of
      neutron stars. Further, we show that the critical collapse can occur due to a
      change of the EOS, without fine-tuning of initial data. This opens the
      possibility that a neutron-star-like compact object, not just those formed in a
      collision, may undergo a critical collapse in processes which slowly change the
      EOS, such as cooling.

PMID- 17501178
TI  - Ising analogue to compact-star matter.
AB  - By constructing an Ising analogue of compact-star matter at subsaturation density
      we explored the effect of Coulomb frustration on the nuclear liquid-gas phase
      transition. Our conclusion is twofold. First, the range of temperatures where
      inhomogeneous phases form expands with increasing Coulomb-field strength. Second,
      within the approximation of uniform electron distribution, the limiting point
      upon which the phase-coexistence region ends does not exhibit any critical
      behavior. Possible astrophysics consequences and thermodynamical connections are
      discussed.

PMID- 17501179
TI  - Predicting solar cycle 24 with a solar dynamo model.
AB  - Whether or not the upcoming cycle 24 of solar activity will be strong is being
      hotly debated. The solar cycle is produced by a complex dynamo mechanism. We
      model the last few solar cycles by "feeding" observational data of the Sun's
      polar magnetic field into our solar dynamo model. Our results fit the observed
      sunspot numbers of cycles 21-23 reasonably well and predict that cycle 24 will be
      about 35% weaker than cycle 23.

PMID- 17501180
TI  - Particle-physics implications of a recent test of the gravitational inverse
      square law.
AB  - We use data from our recent search for violations of the gravitational inverse
      square law to constrain dilaton, radion, and chameleon exchange forces as well as
      arbitrary vector or scalar Yukawa interactions. We test the interpretation of the
      PVLAS Collaboration effect and a conjectured "fat-graviton" scenario and
      constrain the gamma_{5} couplings of pseuodscalar bosons and arbitrary power-law
      interactions.

PMID- 17501181
TI  - Measures on transitions for cosmology from eternal inflation.
AB  - We argue that, in the context of eternal inflation in the landscape, making
      predictions for cosmological--and possibly particle physics--observables requires
      a measure on the possible cosmological histories as opposed to one on the vacua
      themselves. If significant slow-roll inflation occurs, the observables are
      generally determined by the history after the last transition between metastable
      vacua. Hence, we start from several existing measures for counting vacua and
      develop measures for counting the transitions between vacua.

PMID- 17501182
TI  - Are f(R) dark energy models cosmologically viable?
AB  - All f(R) modified gravity theories are conformally identical to models of
      quintessence in which matter is coupled to dark energy with a strong coupling.
      This coupling induces a cosmological evolution radically different from standard
      cosmology. We find that, in all f(R) theories where a power of R is dominant at
      large or small R (which include most of those proposed so far in the literature),
      the scale factor during the matter phase grows as t(1/2) instead of the standard
      law t(2/3). This behavior is grossly inconsistent with cosmological observations
      (e.g., Wilkinson Microwave Anisotropy Probe), thereby ruling out these models
      even if they pass the supernovae test and can escape the local gravity
      constraints.

PMID- 17501183
TI  - Signal for an extra-dimensional model of flavor at the Large Hadron Collider.
AB  - In Randall-Sundrum models with gauge bosons and fermions in the extra-dimensional
      bulk, it is possible to build models of flavor by localizing the fermions in the
      extra dimension. Since the Higgs boson must be localized at or close to the TeV
      scale fixed point, heavier fermions must be localized close to this brane. The
      first Kaluza-Klein excitations of the gauge bosons are also TeV-localized, so
      they have stronger couplings to heavier fermions leading to tree-level flavor
      violating couplings. We investigate the potential of the Large Hadron Collider to
      observe flavor violation in single top production at very high invariant masses,
      in addition to the observation of the corresponding t-t[over] resonance. We
      conclude that the Large Hadron Collider will be able to observe tree-level flavor
      violation in single top production, probing Kaluza-Klein masses at least as large
      as 2 TeV, as well as a very interesting region of the parameters.

PMID- 17501184
TI  - Ultraviolet properties of maximal supergravity.
AB  - We argue that recent results in string perturbation theory indicate that the four
      graviton amplitude of four-dimensional N=8 supergravity might be ultraviolet
      finite up to eight loops. We similarly argue that the h-loop M-graviton amplitude
      might be finite for h<7+M/2.

PMID- 17501185
TI  - Test of the anti-de Sitter-space/conformal-field-theory correspondence using high
      spin operators.
AB  - In two remarkable recent papers the planar perturbative expansion was proposed
      for the universal function of the coupling appearing in the dimensions of high
      spin operators of the N=4 super Yang-Mills theory. We study numerically the
      integral equation derived by Beisert, Eden, and Staudacher, which resumes the
      perturbative series. In a confirmation of the anti-de Sitter-space/conformal
      field-theory (AdS/CFT) correspondence, we find a smooth function whose two
      leading terms at strong coupling match the results obtained for the semiclassical
      folded string spinning in AdS5. We also make a numerical prediction for the third
      term in the strong coupling series.

PMID- 17501186
TI  - Fourth generation CP violation effects on B-->Kpi, phiK, and rhoK in next-to
      leading-order perturbative QCD.
AB  - We study the effect from a sequential fourth generation quark on penguin
      dominated two-body nonleptonic B meson decays in the next-to-leading order
      perturbative QCD formalism. With an enhancement of the color-suppressed tree
      amplitude and possibility of a new CP phase in the electroweak penguin amplitude,
      we can account better for A(CP)(B(0)-->K+ pi-)-A(CP)(B+-->K+ pi0). Taking
      |V(t's)V(t'b)| approximately 0.02 with a phase just below 90 degrees, which is
      consistent with the b-->sl+ l- rate and the B(s) mixing parameter Deltam(B)(s),
      we find a downward shift in the mixing-induced CP asymmetries of B(0)-->K(S)(pi
      0) and phi(K)(S). The predicted behavior for B(0)-->rho(0)(K)(S) is opposite.

PMID- 17501187
TI  - Light scalars coupled to photons and non-newtonian forces.
AB  - A particle phi coupling to two photons couples also radiatively to charged
      particles, like protons. If the particle is a light scalar, this induced coupling
      leads to spin-independent non-Newtonian forces. We show that the experimental
      constraints on exotic, fifth-type forces lead to stringent constraints on the
      phigammagamma coupling. We discuss the impact on the recent PVLAS results and the
      role of paraphoton models introduced to solve the PVLAS-CAST puzzle.

PMID- 17501188
TI  - Observation of the decay B(0)-->J/psieta.
AB  - We report the first observation of B(0)-->J/psieta decay. These results are
      obtained from a data sample that contains 449 x10(6) BB[over] pairs accumulated
      at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric
      energy e(+)e(-) collider. We observe a signal with a significance of 8.1 sigma
      and obtain a branching fraction of (9.5+/-1.7(stat)+/-0.8(syst)) x 10(-6).

PMID- 17501192
TI  - Proton spin structure in the resonance region.
AB  - We have examined the spin structure of the proton in the region of the nucleon
      resonances (1.085 GeV<W<1.910 GeV) at an average four momentum transfer of Q2=1.3
      GeV2. Using the Jefferson Lab polarized electron beam, a spectrometer, and a
      polarized solid target, we measured the asymmetries A|| and A(perpendicular) to
      high precision, and extracted the asymmetries A1 and A2, and the spin structure
      functions g1 and g2. We found a notably nonzero A(perpendicular), significant
      contributions from higher-twist effects, and only weak support for polarized
      quark-hadron duality.

PMID- 17501190
TI  - Search for invisible decay of the Upsilon(1S).
AB  - We report results of a search for the invisible decay of the Upsilon(1S) via the
      Upsilon(3S)-->pi+ pi- Upsilon(1S) transition using a data sample of 2.9 fb-1 at
      the Upsilon(3S) resonance. The data were collected with the Belle detector at the
      KEKB asymmetric-energy e+ e- collider. No signal is found, and an upper limit for
      the branching fraction at the 90% confidence level is determined to be
      B(Upsilon(1S)-->invisible)<2.5 x 10(-3).

PMID- 17501194
TI  - Tensor forces and the ground-state structure of nuclei.
AB  - Two-nucleon momentum distributions are calculated for the ground states of nuclei
      with mass number A< or =8, using variational Monte Carlo wave functions derived
      from a realistic Hamiltonian with two- and three-nucleon potentials. The momentum
      distribution of np pairs is found to be much larger than that of pp pairs for
      values of the relative momentum in the range (300-600) MeV/c and vanishing total
      momentum. This order of magnitude difference is seen in all nuclei considered and
      has a universal character originating from the tensor components present in any
      realistic nucleon-nucleon potential. The correlations induced by the tensor force
      strongly influence the structure of np pairs, which are predominantly in
      deuteronlike states, while they are ineffective for pp pairs, which are mostly in
      1S0 states. These features should be easily observable in two-nucleon knockout
      processes, such as A(e,e'np) and A(e,e'pp).

PMID- 17501195
TI  - Empirical proton-neutron interactions and nuclear density functional theory:
      global, regional, and local comparisons.
AB  - Calculations of nuclear masses, using nuclear density functional theory, are
      presented for even-even nuclei spanning the nuclear chart. The resulting binding
      energy differences can be interpreted in terms of valence proton-neutron
      interactions. These are compared globally, regionally, and locally with empirical
      values. Overall, excellent agreement is obtained. Discrepancies highlight
      neglected degrees of freedom and can point to improved density functionals.

PMID- 17501197
TI  - Optical pumping of trapped neutral molecules by blackbody radiation.
AB  - Optical pumping by blackbody radiation is a feature shared by all polar molecules
      and fundamentally limits the time that these molecules can be kept in a single
      quantum state in a trap. To demonstrate and quantify this, we have monitored the
      optical pumping of electrostatically trapped OH and OD radicals by room
      temperature blackbody radiation. Transfer of these molecules to rotationally
      excited states by blackbody radiation at 295 K limits the 1/e trapping time for
      OH and OD in the X(2)Pi(3/2), v" =0, J"=3/2(f) state to 2.8 and 7.1 s,
      respectively.

PMID- 17501196
TI  - Observation of a rotational band in the odd-Z transfermium nucleus 101251Md.
AB  - A rotational band has been unambiguously observed in an odd-proton transfermium
      nucleus for the first time. An in-beam gamma-ray spectroscopic study of 101/251Md
      has been performed using the gamma-ray array JUROGAM combined with the gas-filled
      separator RITU and the focal plane device GREAT. The experimental results,
      compared to Hartree-Fock-Bogolyubov calculations, lead to the interpretation that
      the rotational band is built on the [521]1/2(-) Nilsson state.

PMID- 17501198
TI  - Three-body recombination of atomic ions with slow electrons.
AB  - Using the time-dependent wave-packets method, we have quantum mechanically
      investigated the three-body recombination process for electron energies varying
      from 10 to 0.01 eV. The classical "bottleneck" prediction on the probable
      population was confirmed by our S-wave quantum calculations for electron kinetic
      energies (K(E)) as low as 0.1 eV. But for K(E)<0.1 eV, the quantum three-body
      recombination tends to populate lower n levels than the classical theory
      predicted. We also find that, in the same n level, the recombination tends to
      populate higher angular-momentum states with K(E) decreasing. These results may
      shed light on the intrinsic dynamics of both ultracold plasmas and frozen Rydberg
      gases.

PMID- 17501199
TI  - Liquid transport due to light scattering.
AB  - Using experiments and theory, we show that light scattering by inhomogeneities in
      the index of refraction of a fluid can drive a large-scale flow. The experiment
      uses a near-critical, phase-separated liquid, which experiences large
      fluctuations in its index of refraction. A laser beam traversing the liquid
      produces a interface deformation on the scale of the experimental setup and can
      cause a liquid jet to form. We demonstrate that the deformation is produced by a
      scattering-induced flow by obtaining good agreements between the measured
      deformations and those calculated assuming this mechanism.

PMID- 17501200
TI  - Electron-spin-dependent terahertz light transport in spintronic-plasmonic media.
AB  - In this Letter, we demonstrate that electron spin can influence near-field
      mediated light propagation through a dense ensemble of subwavelength bimetallic
      ferromagnetic/nonmagnetic microparticles. In particular, we show that
      ferromagnetic particles coated with nonmagnetic metal nanolayers exhibit an
      enhanced magnetic field controlled attenuation of the electromagnetic field
      propagated through the sample. The mechanism is related to dynamic,
      electromagnetically induced electron spin accumulation in the nonmagnet. The
      discovery of an electron spin phenomenon in the light interaction with metallic
      particles opens the door to the marriage of spintronic and plasmonic technologies
      and could pave the way for the development of light-based devices that exploit
      the electron spin state.

PMID- 17501201
TI  - Correlation effects in disordered metallic photonic crystal slabs.
AB  - We analyze the influence of correlations on the optical properties of disordered
      metallic photonic crystal slabs experimentally and theoretically. Different
      disorder models with different nearest-neighbor correlations are considered. We
      present a theory that allows us to quantitatively calculate the optical
      properties of the different samples. We find that different kinds of correlations
      produce characteristic spectral features such as peak reduction and inhomogeneous
      broadening. These features are caused by reduced excitation efficiencies and the
      excitation of multiple resonances.

PMID- 17501203
TI  - Acoustic analogue of electronic BLOCH oscillations and resonant Zener tunneling
      in ultrasonic superlattices.
AB  - We demonstrate the existence of Bloch oscillations of acoustic fields in sound
      propagation through a superlattice of water cavities and layers of methyl
      methacrylate. To obtain the acoustic equivalent of a Wannier-Stark ladder, we
      employ a set of cavities with different thicknesses. Bloch oscillations are
      observed as time-resolved oscillations of transmission in a direct analogy to
      electronic Bloch oscillations in biased semiconductor superlattices. Moreover,
      for a particular gradient of cavity thicknesses, an overlap of two acoustic
      minibands occurs, which results in resonant Zener-like transmission enhancement.

PMID- 17501202
TI  - Origin of bursting through homoclinic spike adding in a neuron model.
AB  - The origin of spike adding in bursting activity is studied in a reduced model of
      the leech heart interneuron. We show that, as the activation kinetics of the slow
      potassium current are shifted towards depolarized membrane potential values, the
      bursting phase accommodates incrementally more spikes into the train. This
      phenomenon is attested to be caused by the homoclinic bifurcations of a saddle
      periodic orbit setting the threshold between the tonic spiking and quiescent
      phases of the bursting. The fundamentals of the mechanism are revealed through
      the analysis of a family of the onto Poincare return mappings.

PMID- 17501204
TI  - Large-scale circulation model for turbulent Rayleigh-Benard convection.
AB  - A model for the large-scale-circulation (LSC) of turbulent Rayleigh-Benard
      convection in cylindrical samples is presented. It consists of two physically
      motivated stochastic ordinary differential equations, one each for the strength
      and the azimuthal orientation of the LSC. Stochastic forces represent
      phenomenologically the influence of turbulent fluctuations. Consistent with
      measurements, the model yields an azimuthally meandering LSC with occasional
      rotations, and with more rare cessations. As in experiment, cessations have a
      uniform distribution of LSC orientation changes.

PMID- 17501205
TI  - Splitting of a liquid jet.
AB  - We demonstrate that a flowing liquid jet can be controllably split into two
      separate subfilaments through the application of a sufficiently strong tangential
      stress to the surface of the jet. In contrast, normal stresses can never split a
      liquid jet. We apply these results to observations of uncontrolled splitting of
      jets in electric fields. The experimental realization of controllable jet
      splitting would provide an entirely novel route for producing small polymeric
      fibers.

PMID- 17501206
TI  - Electro-flow focusing: the high-conductivity low-viscosity limit.
AB  - Electro-flow focusing, a technique combining the features of electrospray (ES)
      and flow focusing (FF), provides a reliable tool to reach parametrical
      microjetting ranges not attainable by ES or FF alone under specific operational
      regimes (liquid properties and flow rate). In this Letter, we provide not only a
      closed theoretical model predicting the diameter of a high electrical
      conductivity electro-flow focused liquid microjet, but also its convective or
      absolute instability, linked to the jetting-to-dripping transition and the
      minimum liquid flow rate that can be ejected in steady jetting regime, in which
      the smallest droplets are issued. Good agreement is found with experimental
      values.

PMID- 17501208
TI  - Observation of kinetic plasma jets in a coronal-loop simulation experiment.
AB  - Under certain conditions an intense kinetic plasma jet is observed to emerge from
      the apex of laboratory simulations of coronal plasma loops. Analytic and
      numerical models show that these jets result from a particle orbit instability in
      a helical magnetic field whereby magnetic forces radially eject rather than
      confine ions with sufficiently large countercurrent axial velocity.

PMID- 17501207
TI  - Quenching of the nonlocal electron heat transport by large external magnetic
      fields in a laser-produced plasma measured with imaging thomson scattering.
AB  - We present a direct measurement of the quenching of nonlocal heat transport in a
      laser-produced plasma by applying large external magnetic fields (>10 T). The
      temporally resolved Thomson-scattering measurements of the electron temperature
      profile show that the heat front propagation transverse to a high-power laser
      beam is slowed resulting in extremely strong local heating. We find agreement
      with hydrodynamic modeling when including a magnetic field model that self
      consistently evolves the fields in the plasma.

PMID- 17501193
TI  - Evidence for a long-range component in the pion emission source in Au+Au
      collisions at sqrt sNN=200 GeV.
AB  - Emission source functions are extracted from correlation functions constructed
      from charged pions produced at midrapidity in Au+Au collisions at sqrt[s(NN)]=200
      GeV. The source parameters extracted from these functions at low k(T) give first
      indications of a long tail for the pion emission source. The source extension
      cannot be explained solely by simple kinematic considerations. The possible role
      of a halo of secondary pions from resonance emissions is explored.

PMID- 17501209
TI  - Superfluidity of grain boundaries in solid 4He.
AB  - By large-scale quantum Monte Carlo simulations we show that grain boundaries in
      4He crystals are generically superfluid at low temperature, with a transition
      temperature of the order of approximately 0.5 K at the melting pressure;
      nonsuperfluid grain boundaries are found only for special orientations of the
      grains. We also find that close vicinity to the melting line is not a necessary
      condition for superfluid grain boundaries, and a grain boundary in direct contact
      with the superfluid liquid at the melting curve is found to be mechanically
      stable and the grain-boundary superfluidity observed by Sasaki et al. [Science
      313, 1098 (2006)10.1126/science.1130879] is not just a crack filled with
      superfluid.

PMID- 17501189
TI  - Search for anomalous production of multilepton events in pp collisions at sqrt
      s=1.96 TeV.
AB  - We report a search for the anomalous production of events with multiple charged
      leptons in pp[over] collisions at sqrt[s]=1.96 TeV using a data sample
      corresponding to an integrated luminosity of 346 pb(-1) collected by the CDF II
      detector at the Fermilab Tevatron. The search is divided into three-lepton and
      four-or-more-lepton data samples. We observe six events in the three-lepton
      sample and zero events in the > or =4-lepton sample. Both numbers of events are
      consistent with standard model background expectations. Within the framework of
      an R-parity-violating supergravity model, the results are interpreted as mass
      limits on the lightest neutralino (chi[over](1)(0)) and chargino (chi[over](1+/-)
      particles. For one particular choice of model parameters, the limits are
      M(chi[over](1)(0)>110 GeV/c2 and M(chi[over](1+/-)>203 GeV/c2 at 95% confidence
      level; the variation of these mass limits with model parameters is presented.

PMID- 17501210
TI  - Growing perfect decagonal quasicrystals by local rules.
AB  - A local growth algorithm for a decagonal quasicrystal is presented. We show that
      a perfect Penrose tiling (PPT) layer can be grown on a decapod tiling layer by a
      three dimensional (3D) local rule growth. Once a PPT layer begins to form on the
      upper layer, successive 2D PPT layers can be added on top resulting in a perfect
      decagonal quasicrystalline structure in bulk with a point defect only on the
      bottom surface layer. Our growth rule shows that an ideal quasicrystal structure
      can be constructed by a local growth algorithm in 3D, contrary to the necessity
      of nonlocal information for a 2D PPT growth.

PMID- 17501191
TI  - Analysis of the quantum numbers J(PC) of the X(3872) particle.
AB  - We present an analysis of angular distributions and correlations of the X(3872)
      particle in the exclusive decay mode X(3872)-->J/psipi+ pi- with J/psi-->mu+ mu-.
      We use 780 pb-1 of data from pp[over ] collisions at sqrt[s]=1.96 TeV collected
      with the CDF II detector at the Fermilab Tevatron. We derive constraints on spin,
      parity, and charge conjugation parity of the X(3872) particle by comparing
      measured angular distributions of the decay products with predictions for
      different J(PC) hypotheses. The assignments J(PC)=1++ and 2-+ are the only ones
      consistent with the data.

PMID- 17501211
TI  - Pressure-induced structural transformation in radiation-amorphized zircon.
AB  - We study the response of a radiation-amorphized material to high pressure. We
      have used zircon ZrSiO4 amorphized by natural radiation over geologic times, and
      have measured its volume under high pressure, using the precise strain-gauge
      technique. On pressure increase, we observe apparent softening of the material,
      starting from 4 GPa. Using molecular dynamics simulation, we associate this
      softening with the amorphous-amorphous transformation accompanied by the increase
      of local coordination numbers. We observe permanent densification of the quenched
      sample and a nontrivial "pressure window" at high temperature. These features
      point to a new class of amorphous materials that show a response to pressure
      which is distinctly different from that of crystals.

PMID- 17501212
TI  - Heterogeneous diffusion in a reversible gel.
AB  - We introduce a microscopically realistic model of a physical gel and use computer
      simulations to study its static and dynamic properties at thermal equilibrium.
      The phase diagram comprises a sol phase, a coexistence region ending at a
      critical point, a gelation line determined by geometric percolation, and an
      equilibrium gel phase unrelated to phase separation. The global structure of the
      gel is homogeneous, but the stress is only supported by a fractal network. The
      gel dynamics is highly heterogeneous and we propose a theoretical model to
      quantitatively describe dynamic heterogeneity in gels. We elucidate several
      differences between the dynamics of gels and that of glass formers.

PMID- 17501213
TI  - Low-temperature ultrafast mobility in systems with long-range repulsive
      interactions: Pb/Si(111).
AB  - A realization of the numerous phases predicted in systems with long-range
      repulsive interactions was recently found in Pb/Si(111). Surprisingly, these
      numerous phases can be grown at low temperatures approximately 40 K over
      macroscopic distances. This unusual observation can be explained from theoretical
      calculations of the collective diffusion coefficient D(c) in systems with long
      range repulsive interactions. Instead of a gradual dependence of D(c) on
      coverage, it was found that D(c) has sharp maxima at low temperatures for every
      stable phase (i.e., for every rational value of the coverage theta=p/q) in
      agreement with the experiment.

PMID- 17501214
TI  - Colossal shear-strength enhancement of low-density cubic BC2N by nanoindentation.
AB  - Recently synthesized low-density cubic BC2N exhibits surprisingly high shear
      strength inferred by nanoindentation in stark contrast to its relatively low
      elastic moduli. We show by first-principles calculation that this intriguing
      phenomenon can be ascribed to a novel structural hardening mechanism due to the
      compressive stress beneath the indenter. It significantly strengthens the weak
      bonds connecting the shear planes, yielding a colossal enhancement in shear
      strength. The resulting biaxial stress state produces atomistic fracture modes
      qualitatively different from those under pure shear stress. These results provide
      the first consistent explanation for a variety of experiments on the low-density
      cubic BC2N phase across a large range of strain.

PMID- 17501215
TI  - Possible approach to overcome the doping asymmetry in wideband gap
      semiconductors.
AB  - The asymmetry doping problem has severely hindered the potential applications of
      many wideband gap (WBG) materials. Here, we propose a possible approach to
      overcome this long-standing doping asymmetry problem for WBG semiconductors. Our
      approach is based on the reduction of the ionization energies of dopants through
      introduction and effective doping of mutually passivated impurity bands, which
      can be realized by doping the host with passive donor-acceptor complexes or
      isovalent impurities. Our density-functional theory calculations demonstrate that
      this approach provides excellent explanations for the n-type doping of diamond
      and p-type doping of ZnO, which could not be understood by previous theories. In
      principle, this approach can be applied to any WBG semiconductors and therefore
      will open a broad vista for the application of WBG materials.

PMID- 17501216
TI  - Shock waves in polycrystalline iron.
AB  - The propagation of shock waves through polycrystalline iron is explored by large
      scale atomistic simulations. For large enough shock strengths the passage of the
      wave causes the body-centered-cubic phase to transform into a close-packed phase
      with most structure being isotropic hexagonal-close-packed (hcp) and, depending
      on shock strength and grain orientation, some fraction of face-centered-cubic
      (fcc) structure. The simulated shock Hugoniot is compared to experiments. By
      calculating the extended x-ray absorption fine structure (EXAFS) directly from
      the atomic configurations, a comparison to experimental EXAFS measurements of
      nanosecond-laser shocks shows that the experimental data is consistent with such
      a phase transformation. However, the atomistically simulated EXAFS spectra also
      show that an experimental distinction between the hcp or fcc phase is not
      possible based on the spectra alone.

PMID- 17501217
TI  - A nanoscale gas state.
AB  - We show that a very thin (5-80 nm) gas phase can exist for a long time (>1 h) at
      the interface between a hydrophobic solid and water. We create the gas phase from
      CO2, which allows us to determine the chemical identity, phase state, and density
      via infrared spectroscopy. The average density reveals that the gas is at
      approximately atmospheric pressure, which explains the unexpectedly long lifetime
      of the gas phase under ambient conditions. The nanoscale gas phase is
      reproducibly created under conditions where gas solubility is varied.

PMID- 17501218
TI  - Probing enantioselectivity with x-ray photoelectron spectroscopy and density
      functional theory.
AB  - The enantioselectivity of gold is investigated by x-ray photoelectron
      spectroscopy (XPS) and density functional theory (DFT). Cysteine molecules on a
      chiral Au(17 11 9);{S} surface show enantiospecific core level binding energies
      in the amino and in the thiol group. The sign and order of magnitude of the XPS
      core level shifts is reproduced by DFT. Identical preparations of D- and L
      cysteine layers lead to D-cysteine molecules in the pure NH2 form, while a small
      portion of L-cysteine molecules maintains a hydrogen rich amino group (NH3). This
      implies enantiospecific adsorption reaction pathways and is consistent with DFT
      that indicates an activated hydrogen abstraction reaction from the amino group,
      which is downhill for D-cysteine.

PMID- 17501219
TI  - From homogeneous to heterogeneous nucleation of chain molecules under nanoscopic
      cylindrical confinement.
AB  - The crystallization of monodisperse linear polyethylene confined in nanoporous
      alumina is investigated with the calorimetric measurements. We observe a drastic
      change in crystallization behavior, specifically nucleation, with a decrease in
      the pore diameter. Crystallization in relatively larger pores with the diameters
      of 62 and 110 nm occurs at lower temperatures within a very narrow range, whereas
      crystallization in smaller pores with diameters of 15-48 nm occurs at a higher
      and broad range of temperatures. Nucleation and crystallization kinetics in
      nanopores is discussed based on classical nucleation theory as well as the Avrami
      theory.

PMID- 17501220
TI  - Cl insertion on Si(100)-(2x1): etching under conditions of supersaturation.
AB  - We use scanning tunneling microscopy to show that Cl2 dosing of Cl-saturated
      Si(100)-(2x1) surfaces at elevated temperature leads to uptake beyond
      "saturation" and allows access to a new etching pathway. This process involves Cl
      insertion in Si-Si dimer bonds or backbonds, diffusion of the inserted Cl, and
      ultimately desorption of SiCl2. Investigations into the etch kinetics reveal that
      insertion occurs via a novel form of Cl2 dissociative chemisorption that is
      mediated by dangling bond sites. Upon dissociation, one Cl atom adsorbs at the
      dangling bond while the other can insert.

PMID- 17501221
TI  - Epitaxial silicon oxynitride layer on a 6H-SiC(0001) surface.
AB  - Hydrogen-gas etching of a 6H-SiC(0001) surface and subsequent annealing in
      nitrogen atmosphere leads to the formation of a silicon oxynitride (SiON)
      epitaxial layer. A quantitative low-energy electron diffraction analysis revealed
      that the SiON layer has a hetero-double-layer structure: a silicate monolayer on
      a silicon nitride monolayer via Si-O-Si bridge bonds. There are no dangling bonds
      in the unit cell, which explains the fact that the structure is robust against
      air exposure. Scanning tunneling spectroscopy measured on the SiON layer shows a
      bulk SiO2-like band gap of approximately 9 eV. Great potential of this new
      epitaxial layer for device applications is described.

PMID- 17501222
TI  - Unified origin for the 3D magnetism and superconductivity in NaxCoO2.
AB  - We analyze the origin of the three-dimensional (3D) magnetism observed in
      nonhydrated Na-rich Na(x)CoO2 within an itinerant spin picture using a 3D Hubbard
      model. The origin is identified as the 3D nesting between the inner and outer
      portions of the Fermi surface, which arise due to the local minimum structure of
      the a(1g) band at the Gamma-A line. The calculated spin wave dispersion
      strikingly resembles the neutron scattering result. We argue that this 3D
      magnetism and the spin fluctuations responsible for superconductivity in the
      hydrated systems share essentially the same origin.

PMID- 17501223
TI  - Electrical resistivity near Pomeranchuk instability in two dimensions.
AB  - We analyze the dc charge transport in the quantum critical regime near a d-wave
      Pomeranchuk instability in two dimensions. The transport decay rate is linear in
      temperature everywhere on the Fermi surface except at cold spots on the Brillouin
      zone diagonal. For pure systems, this leads to a dc resistivity proportional to
      T(3/2) in the low-temperature limit. In the presence of impurities the residual
      impurity resistance at T=0 is approached linearly at low temperatures.

PMID- 17501224
TI  - Current and strain-induced spin polarization in InGaN/GaN superlattices.
AB  - The lateral current-induced spin polarization in InGaN/GaN superlattices (SLs)
      without an applied magnetic field is reported. The fact that the sign of the
      nonequilibrium spin changes as the current reverses and is opposite for the two
      edges provides a clear signature for the spin Hall effect. In addition, it is
      discovered that the spin Hall effect can be strongly manipulated by the internal
      strains. A theoretical work has also been developed to understand the observed
      strain-induced spin polarization. Our result paves an alternative way for the
      generation of spin polarized current.

PMID- 17501225
TI  - Structure and transport characteristics of modified DNA with magnetic ions.
AB  - Motivated by recent experiments we study the alignment of magnetic ions Cu2+ and
      Mn2+ along the modified DNA helix. We find that doping with magnetic ions induces
      conducting states in the gap region of natural DNA. These magnetic ions are found
      to interact ferromagnetically along the DNA helix. Calculations of optical
      conductivity about the helical axis suggest that the origin of magnetic
      characteristics depend on the metal ions; while Cu-DNA favors in-plane sigma-like
      delocalization over the base pairs, the Mn-DNA favors out-of-plane (pi)
      delocalizations. Such an alignment of magnetic ions offers promising perspectives
      for creating low-dimensional polarized spin channel within the DNA helix.

PMID- 17501226
TI  - Weak antilocalization in epitaxial graphene: evidence for chiral electrons.
AB  - Transport in ultrathin graphite grown on silicon carbide is dominated by the
      electron-doped epitaxial layer at the interface. Weak antilocalization in 2D
      samples manifests itself as a broad cusplike depression in the longitudinal
      resistance for magnetic fields 10 mT<B<5 T. An extremely sharp weak-localization
      resistance peak at B=0 is also observed. These features quantitatively agree with
      graphene weak-(anti)localization theory implying the chiral electronic character
      of the samples. Scattering contributions from the trapped charges in the
      substrate and from trigonal warping due to the graphite layer on top are
      tentatively identified. The Shubnikov-de Haas oscillations are remarkably small
      and show an anomalous Berry's phase.

PMID- 17501227
TI  - Spatial imaging of two-dimensional electronic states in semiconductor quantum
      wells.
AB  - We measure the spatial distribution of the local density of states (LDOS) at
      cleaved surfaces of InAs/GaSb isolated quantum wells and double quantum wells
      (DQWs) by low-temperature scanning tunneling spectroscopy. Distinct standing wave
      patterns of LDOS corresponding to subbands are observed. These LDOS patterns and
      subband energies agree remarkably well with simple calculations with tip-induced
      band bending. Furthermore, for the DQWs, coupling of electronic states between
      the quantum wells is also clearly observed.

PMID- 17501228
TI  - Stochastic dynamics of a Josephson junction threshold detector.
AB  - We generalize the stochastic path integral formalism by considering Hamiltonian
      dynamics in the presence of general Markovian noise. Kramers' solution of the
      activation rate for escape over a barrier is generalized for non-Gaussian driving
      noise in both the overdamped and underdamped limit. We apply our general results
      to a Josephson junction detector measuring the electron counting statistics of a
      mesoscopic conductor. The activation rate dependence on the third current
      cumulant includes an additional term originating from the backaction of the
      measurement circuit.

PMID- 17501229
TI  - Surface double layer on (001) surfaces of alkali halide crystals: a scanning
      force microscopy study.
AB  - In this Letter we consider the surface double layer on (001) surfaces of UHV
      cleaved and annealed alkali halide crystals (KCl, NaCl), which we studied with
      dynamic scanning force microscopy and Kelvin probe force microscopy. Kelvin
      images show bright and round patches at corner sites and steps. Images with
      atomic resolution always show kinks at the latter step sites. Our findings are in
      perfect agreement with the long-standing picture that, due to the presence of
      divalent impurity ions, the surface carries a net negative surface charge
      originating from negative cation vacancies at kinks.

PMID- 17501230
TI  - Enhancement of carrier mobility in semiconductor nanostructures by dielectric
      engineering.
AB  - We propose a technique for achieving large improvements in carrier mobilities in
      2- and 1-dimensional semiconductor nanostructures by modifying their dielectric
      environments. We show that by coating the nanostructures with high-kappa
      dielectrics, scattering from Coulombic impurities can be strongly damped. Though
      screening is also weakened, the damping of Coulombic scattering is much larger,
      and the resulting improvement in mobilities of carriers can be as much as an
      order of magnitude for thin 2D semiconductor membranes, and more for
      semiconductor nanowires.

PMID- 17501231
TI  - Anisotropy of the Sommerfeld coefficient in magnesium diboride single crystals.
AB  - The anisotropic field dependence of the Sommerfeld coefficient gamma has been
      measured down to B-->0 by combining specific heat and Hall probe magnetization
      measurements in MgB2 single crystals. We find that gamma(B,theta) is the sum of
      two contributions arising from the sigma and pi band, respectively. We show that
      gammasigma(B,theta)=B/Bc2(theta) where
      Bc2(theta)=Bc2ab/sqrt[sin2theta+Gamma2cos2theta] with Gamma approximately 5.4
      (theta being the angle between the applied field and the c axis) and
      gammapi(B,theta)=gammapi(B)=B/Bpi(B). The "critical field" of the pi band Bpi is
      fully isotropic but field dependent increasing from approximately 0.25 T for B<
      or =0.1 T up to 3 T approximately Bc2c for B-->3 T. Because of the coupling of
      the two bands, superconductivity survives in the pi band up to 3 T but is totally
      destroyed above for any orientation of the field.

PMID- 17501232
TI  - Transition from a mixed to a pure d-wave symmetry in superconducting optimally
      doped YBa2Cu3O7-x thin films under applied fields.
AB  - We have probed the Landau levels of nodal quasiparticles by tunneling along a
      nodal direction of (110) oriented YBa2Cu3O7-x thin films with a magnetic field
      applied perpendicular to the CuO2 planes, and parallel to the film's surface. In
      optimally doped films and at low temperature, finite energy nodal states are
      clearly observed in films thinner than the London penetration depth. Above a well
      defined temperature, the order parameter reverts to a pure d-wave symmetry.

PMID- 17501233
TI  - Effect of ferroelectricity on electron transport in Pt/BaTiO3/Pt tunnel
      junctions.
AB  - Based on first-principles calculations, we demonstrate the impact of the electric
      polarization on electron transport in ferroelectric tunnel junctions (FTJs).
      Using a Pt/BaTiO3/Pt FTJ as a model system, we show that the polarization of the
      BaTiO3 barrier leads to a substantial drop in the tunneling conductance due to
      changes in the electronic structure driven by ferroelectric displacements. We
      find a sizable change in the transmission probability across the Pt/BaTiO3
      interface with polarization reversal, a signature of the electroresistance
      effect. These results reveal exciting prospects that FTJs offer as resistive
      switches in nanoscale electronic devices.

PMID- 17501234
TI  - Magnetizing oxides by substituting nitrogen for oxygen.
AB  - We describe a possible pathway to new magnetic materials with no conventional
      magnetic elements present. The substitution of nitrogen for oxygen in simple
      nonmagnetic oxides leads to holes in N 2p states which form local magnetic
      moments. Because of the very large Hund's rule coupling of Nitrogen and O 2p
      electrons and the rather extended spatial extent of the wave functions these
      materials are predicted to be ferromagnetic metals or small band gap insulators.
      Experimental studies support the theoretical calculations with regard to the
      basic electronic structure and the formation of local magnetic moments. It
      remains to be seen if these materials are magnetically ordered and, if so, below
      what temperature.

PMID- 17501235
TI  - Understanding the insulating phase in colossal magnetoresistance manganites:
      shortening of the Jahn-Teller long-bond across the phase diagram of La1-xCaxMnO3.
AB  - The detailed evolution of the magnitude of the local Jahn-Teller (JT) distortion
      in La(1-x)Ca(x)MnO3 is obtained across the phase diagram for 0< or =x< or =0.5
      from high-quality neutron diffraction data using the atomic pair distribution
      function method. A local JT distortion is observed in the insulating phase for
      all Ca concentrations studied. However, in contrast with earlier local structure
      studies, its magnitude is not constant, but decreases continuously with
      increasing Ca content. This observation is at odds with a simple small-polaron
      picture for the insulating state.

PMID- 17501236
TI  - Antiferromagnetic interactions in single crystalline Zn1-xCoxO thin films.
AB  - In a rather contradictory situation regarding magnetic data on Co-doped ZnO, we
      have succeeded in fabricating high-quality single crystalline Zn(1-x)Co(x)O
      (x=0.003-0.07) thin films. This gives us the possibility, for the first time, to
      examine the intrinsic magnetic properties of ZnO:Co at a quantitative level and
      therefore to address several unsolved problems, the major one being the nature of
      the Co-Co interaction in the ZnO structure.

PMID- 17501237
TI  - Chain breaks and the susceptibility of Sr2Cu1-xPdxO3+delta and other doped quasi
      one-dimensional antiferromagnets.
AB  - We study the magnetic susceptibility of one-dimensional S=1/2 antiferromagnets
      containing nonmagnetic impurities which cut the chain into finite segments. For
      the susceptibility of long anisotropic Heisenberg chain segments with open
      boundaries we derive a parameter-free result at low temperatures using field
      theory methods and the Bethe ansatz. The analytical result is verified by
      comparing with quantum Monte Carlo calculations. We then show that the
      partitioning of the chain into finite segments can explain the Curie-like
      contribution observed in recent experiments on Sr2Cu(1-x)PdxO(3+delta). Possible
      additional paramagnetic impurities seem to play only a minor role.

PMID- 17501238
TI  - Magnetic excitations in multiferroic TbMnO3: evidence for a hybridized soft mode.
AB  - The magnetic excitations in multiferroic TbMnO3 have been studied by inelastic
      neutron scattering in the spiral and sinusoidally ordered phases. At the
      incommensurate magnetic zone center of the spiral phase, we find three low-lying
      magnons whose character has been fully determined using neutron-polarization
      analysis. The excitation at the lowest energy is the sliding mode of the spiral,
      and two modes at 1.1 and 2.5 meV correspond to rotations of the spiral rotation
      plane. These latter modes are expected to couple to the electric polarization.
      The 2.5 meV mode is in perfect agreement with recent infrared-spectroscopy data
      giving strong support to its interpretation as a hybridized phonon-magnon
      excitation.

PMID- 17501239
TI  - Microcanonical approach to the simulation of first-order phase transitions.
AB  - A simple microcanonical strategy for the simulation of first-order phase
      transitions is proposed. At variance with flat-histogram methods, there is no
      iterative parameters optimization nor long waits for tunneling between the
      ordered and the disordered phases. We test the method in the standard benchmark:
      the Q-states Potts model (Q=10 in two dimensions and Q=4 in D=3). We develop a
      cluster algorithm for this model, obtaining accurate results for systems with
      more than 10(6) spins.

PMID- 17501240
TI  - Simultaneous Raman and fluorescence spectroscopy of single conjugated polymer
      chains.
AB  - Simultaneous surface enhanced Raman scattering (SERS) and fluorescence is
      demonstrated from single conjugated polymer chains. As resonance enhancement of
      SERS depends on the spectral overlap of the polymer's absorption and the incident
      laser, resonance Raman and fluorescence effectively probe the absorbing and
      emitting part of the polymer, respectively. The optical phonon energies change
      along the polymer chain, providing a window to spatially track excited state
      relaxation. Whereas a mean spatial redistribution of the excitation is witnessed
      by a change in vibronic fingerprint following interchromophoric energy transfer,
      intrachromophoric exciton self-trapping leaves the vibrations unchanged.

PMID- 17501241
TI  - Counterion-hopping along the backbone of single-stranded DNA in nanometer pores:
      a mechanism for current conduction.
AB  - Molecular dynamics calculations are performed to investigate ionic current
      conduction through nanopores in the presence of single-stranded DNA. We find the
      counterions to be strongly attracted to the phosphate groups of the DNA, with
      resident time on the order of nanoseconds, while coions are strongly excluded.
      The diffusion constant of the counterions is calculated and used to estimate the
      ionic current through the pore, which gives a similar magnitude as in experiment.
      The results suggest a counterion-hopping mechanism along the ssDNA backbone in
      the current conduction through nanopores.

PMID- 17501243
TI  - Stochastic qualifiers of epileptic brain dynamics.
AB  - We evaluate the capability of reconstructing Fokker-Planck equations for an
      improved characterization of electroencephalographic (EEG) recordings from
      epilepsy patients. We derive stochastic qualifiers of brain dynamics that are
      based on specific characteristics of the Kramers-Moyal coefficients estimated
      from the EEG. Analyzing long-lasting multichannel EEG recordings from eight
      patients suffering from focal epilepsies we show that particularly the stochastic
      part of the dynamics can yield valuable information for diagnostic purposes.

PMID- 17501242
TI  - Proton momentum distribution in a protein hydration shell.
AB  - The momentum distribution of protons in the hydration shell of a globular protein
      has been measured through deep inelastic neutron scattering at 180 and 290 K,
      below and above the crossover temperature Tc=1.23Tg, where Tg=219 K is the glass
      transition temperature. It is found that the mean kinetic energy of the water
      hydrogens shows no temperature dependence, but the measurements are accurate
      enough to indicate a sensible change of momentum distribution and effective
      potential felt by protons, compatible with the transition from a single to a
      double potential well. This could support the presence of tunneling effects even
      at room temperature, playing an important role in biological function.

PMID- 17501244
TI  - Modeling the control of fixational eye movements with neurophysiological delays.
AB  - We propose a model for the control of fixational eye movements using time-delayed
      random walks. Fixational eye movements produce random displacements of the
      retinal image to prevent perceptual fading. First, we demonstrate that a
      transition from persistent to antipersistent correlations occurs in data recorded
      from a visual fixation task. Second, we propose and investigate a delayed random
      walk model and get, by comparison of the transition points, an estimate of the
      neurophysiological delay. Differences between horizontal and vertical components
      of eye movements are found which can be explained neurophysiologically. Finally,
      we compare our numerical results with analytic approximations.

PMID- 17501245
TI  - Growth-induced instability in metabolic networks.
AB  - Product-feedback inhibition is a ubiquitous regulatory scheme for maintaining
      homeostasis in living cells. Individual metabolic pathways with product-feedback
      inhibition are stable as long as one pathway step is rate limiting. However,
      pathways are often coupled both by the use of a common substrate and by
      stoichiometric utilization of their products for cell growth. We show that such a
      coupled network with product-feedback inhibition may exhibit limit-cycle
      oscillations which arise via a Hopf bifurcation. Our results highlight novel
      evolutionary constraints on the architecture of metabolism.

PMID- 17501246
TI  - Thermophoresis in colloidal suspensions driven by Marangoni forces.
AB  - In a hydrodynamic approach to thermophoretic transport in colloidal suspensions,
      the solute velocity u and the solvent flow v(r) are derived from Stokes'
      equation, with slip boundary conditions imposed by thermal Marangoni forces. The
      resulting fluid velocity field v(r) significantly differs from that induced by an
      externally driven particle. We find, in particular, that thermophoresis due to
      surface forces is insensitive to hydrodynamic interactions. As a consequence, the
      thermal diffusion coefficient D(T) of polymer solutions is independent of
      molecular weight and concentration.

PMID- 17501247
TI  - Difficulty in the Fermi-liquid-type theory for the in-plane magnetic anisotropy
      of untwinned YBa2Cu3O6.85 superconductors.

PMID- 17501249
TI  - Density of near-extreme events.
AB  - We provide a quantitative analysis of the phenomenon of crowding of near-extreme
      events by computing exactly the density of states (DOS) near the maximum of a set
      of independent and identically distributed random variables. We show that the
      mean DOS converges to three different limiting forms depending on whether the
      tail of the distribution of the random variables decays slower than pure
      exponential, faster than pure exponential, or as a pure exponential function. We
      argue that some of these results would remain valid even for certain correlated
      cases and verify it for power-law correlated stationary Gaussian sequences.
      Satisfactory agreement is found between the near-maximum crowding in the summer
      temperature reconstruction data of western Siberia and the theoretical
      prediction.

PMID- 17501250
TI  - Modification of scattering lengths via magnetic dipole-dipole interactions.
AB  - We propose a new mechanism for tuning an atomic s-wave scattering length. The
      effect is caused by virtual transitions between different Zeeman sublevels via
      magnetic dipole-dipole interactions. These transitions give rise to an effective
      potential, which, in contrast to standard magnetic interactions, has an isotropic
      component and thus affects s-wave collisions.

PMID- 17501251
TI  - Steering, entanglement, nonlocality, and the Einstein-Podolsky-Rosen paradox.
AB  - The concept of steering was introduced by Schrodinger in 1935 as a generalization
      of the Einstein-Podolsky-Rosen paradox for arbitrary pure bipartite entangled
      states and arbitrary measurements by one party. Until now, it has never been
      rigorously defined, so it has not been known (for example) what mixed states are
      steerable (that is, can be used to exhibit steering). We provide an operational
      definition, from which we prove (by considering Werner states and isotropic
      states) that steerable states are a strict subset of the entangled states, and a
      strict superset of the states that can exhibit Bell nonlocality. For arbitrary
      bipartite Gaussian states we derive a linear matrix inequality that decides the
      question of steerability via Gaussian measurements, and we relate this to the
      original Einstein-Podolsky-Rosen paradox.

PMID- 17501252
TI  - Atom interferometer based on phase coherent splitting of Bose-Einstein
      condensates with an integrated magnetic grating.
AB  - We report the phase coherent splitting of Bose-Einstein condensates by means of a
      phase grating produced near the surface of a microelectronic chip. A lattice
      potential with a period of 4 mum is generated by the superposition of static and
      oscillating magnetic fields. Precise control of the diffraction is achieved by
      controlling the currents in the integrated conductors. The interference of
      overlapping diffraction orders is observed after 8 ms of propagation in a
      harmonic trap and subsequent ballistic expansion of the atomic ensemble. By
      analyzing the interference pattern we show a reproducible phase relation between
      the diffraction orders with an uncertainty limited by the resolution of the
      diffraction grating.

PMID- 17501253
TI  - Experimental realization of Deutsch's algorithm in a one-way quantum computer.
AB  - We report the first experimental demonstration of an all-optical one-way
      implementation of Deutsch's quantum algorithm on a four-qubit cluster state. All
      the possible configurations of a balanced or constant function acting on a two
      qubit register are realized within the measurement-based model for quantum
      computation. The experimental results are in excellent agreement with the
      theoretical model, therefore demonstrating the successful performance of the
      algorithm.

PMID- 17501254
TI  - Small accessible quantum information does not imply security.
AB  - The security of quantum key distribution is typically defined in terms of the
      mutual information between the distributed key S and the outcome of an optimal
      measurement applied to the adversary's system. We show that even if this so
      called accessible information is small, the key S might not be secure enough to
      be used in applications such as one-time pad encryption. This flaw is due to a
      locking property of the accessible information: one additional (physical) bit of
      information can increase the accessible information by more than one bit.

PMID- 17501255
TI  - Photon polarization entanglement induced by Biexciton: experimental evidence for
      violation of Bell's inequality.
AB  - We have investigated the polarization entanglement between photon pairs generated
      from a biexciton in a CuCl single crystal via resonant hyperparametric
      scattering. The pulses of a high repetition pump are seen to provide improved
      statistical accuracy and the ability to test Bell's inequality. Our results
      clearly violate the inequality and thus manifest the quantum entanglement and
      nonlocality of the photon pairs. We also analyzed the quantum state of our photon
      pairs using quantum state tomography.

PMID- 17501256
TI  - Accumulation of entanglement in a continuous variable memory.
AB  - We study entanglement accumulation in a memory built out of two continuous
      variable systems interacting with a qubit that mediates their indirect coupling.
      We show that, in contrast with the case of bidimensional Hilbert spaces,
      entanglement superior to one ebit can be accumulated in the memory, even though
      no entangled resource is used. The protocol is immediately implementable and we
      assess the role of the main imperfections.

PMID- 17501257
TI  - Observable entanglement measure for mixed quantum States.
AB  - We quantify an unknown mixed quantum state's entanglement by suitable, local
      parity measurements on its twofold copy. The associated observable qualifies as a
      generalized entanglement witness.

PMID- 17501258
TI  - Computational complexity of projected entangled pair states.
AB  - We determine the computational power of preparing projected entangled pair states
      (PEPS), as well as the complexity of classically simulating them, and generally
      the complexity of contracting tensor networks. While creating PEPS allows us to
      solve PP problems, the latter two tasks are both proven to be #P-complete. We
      further show how PEPS can be used to approximate ground states of gapped
      Hamiltonians and that creating them is easier than creating arbitrary PEPS. The
      main tool for our proofs is a duality between PEPS and postselection which allows
      us to use existing results from quantum complexity.

PMID- 17501259
TI  - Crossover in the slow decay of dynamic correlations in the lorentz model.
AB  - The long-time behavior of transport coefficients in a model for spatially
      heterogeneous media in two and three dimensions is investigated by molecular
      dynamics simulations. The behavior of the velocity autocorrelation function is
      rationalized in terms of a competition of the critical relaxation due to the
      underlying percolation transition and the hydrodynamic power-law anomalies. In
      two dimensions and in the absence of a diffusive mode, another power-law anomaly
      due to trapping is found with an exponent -3 instead of -2. Further, the
      logarithmic divergence of the Burnett coefficient is corroborated in the dilute
      limit; at finite density, however, it is dominated by stronger divergences.

PMID- 17501260
TI  - Fast computation of many-particle hydrodynamic and electrostatic interactions in
      a confined geometry.
AB  - An O(N) method is presented for calculation of hydrodynamic or electrostatic
      interactions between N point particles in a confined geometry. This approach
      splits point forces or sources into a local contribution for which rapidly
      decaying free-space analytical solutions to the Stokes or Poisson equations are
      used, and a global contribution whose effect is determined numerically using a
      fast iterative method. The scheme is applied to Brownian dynamics simulations of
      flowing confined polymer solutions, and the effects of concentration on
      hydrodynamically induced migration phenomena are illustrated.

PMID- 17501261
TI  - Noncontact racK and pinion powered by the lateral Casimir force.
AB  - The lateral Casimir force is employed to propose a design for a potentially wear
      proof rack and pinion with no contact, which can be miniaturized to the
      nanoscale. The robustness of the design is studied by exploring the relation
      between the pinion velocity and the rack velocity in the different domains of the
      parameter space. The effects of friction and added external load are also
      examined. It is shown that the device can hold up extremely high velocities,
      unlike what the general perception of the Casimir force as a weak interaction
      might suggest.

PMID- 17501262
TI  - Demonstration of displacement- and frequency-noise-free laser interferometry
      using bidirectional Mach-Zehnder interferometers.
AB  - We have demonstrated displacement- and frequency-noise-free laser interferometry
      (DFI) by partially implementing a recently proposed optical configuration using
      bidirectional Mach-Zehnder interferometers (MZIs). This partial implementation,
      the minimum necessary to be called DFI, has confirmed the essential feature of
      DFI: the combination of two MZI signals can be carried out in a way that cancels
      displacement noise of the mirrors while maintaining gravitational-wave signals.
      The attained maximum displacement-noise suppression was 45 dB.

PMID- 17501263
TI  - Probing the temperature profile of energy production in the sun.
AB  - The particle kinetic energies of thermonuclear pp fusion in the Sun (Gamow
      energy) produce small changes in the energies of pp solar neutrinos relative to
      those due only to exothermal energetics. This effect may be observable via the
      unique tools of the LENS solar neutrino detector. The temperature profile of
      energy production in the Sun may thus be directly probed for the first time.

PMID- 17501264
TI  - Galactic-cosmic-ray-produced 3He in a ferromanganese crust: any supernova 60Fe
      excess on earth?
AB  - An excess of 60Fe in 2.4-3.2 x 10(6) year old ferromanganese crust (237 KD) from
      the deep Pacific Ocean has been considered as evidence for the delivery of debris
      from a nearby supernova explosion to Earth. Extremely high ;{3}He/;{4}He (up to
      6.12 x 10(-3)) and 3He concentrations (up to 8 x 10(9) atoms/g) measured in 237
      KD cannot be supernova-derived. The helium is produced by galactic cosmic rays
      (GCR) and delivered in micrometeorites that have survived atmospheric entry to be
      trapped by the crust. 60Fe is produced by GCR reactions on Ni in extraterrestrial
      material. The maximum (3)He/(60)Fe of 237 KD (80-850) is comparable to the GCR
      (3)He/(60)Fe production ratio (400-500) predicted for Ni-bearing minerals in iron
      meteorites. The excess 60Fe can be plausibly explained by the presence of
      micrometeorites trapped by the crust, rather than injection from a supernova
      source.

PMID- 17501268
TI  - Energy splitting of the ground-state doublet in the nucleus 229Th.
AB  - The energy splitting of the 229Th ground-state doublet is measured to be 7.6+/
      0.5 eV, significantly greater than earlier measurements. Gamma rays produced
      following the alpha decay of 233U (105 muCi) were counted in the NASA/electron
      beam ion trap x-ray microcalorimeter spectrometer with an experimental energy
      resolution of 26 eV (FWHM). A difference technique was applied to the gamma-ray
      decay of the 71.82 keV level that populates both members of the doublet. A
      positive correction amounting to 0.6 eV was made for the unobserved interband
      decay of the 29.19 keV state (29.19-->0 keV).

PMID- 17501267
TI  - Longitudinal-transverse separations of deep-inelastic structure functions at low
      Q2 for hydrogen and deuterium.
AB  - We report on a study of the longitudinal to transverse cross section ratio,
      R=sigmaL/sigmaT, at low values of x and Q2, as determined from inclusive
      inelastic electron-hydrogen and electron-deuterium scattering data from Jefferson
      Laboratory Hall C spanning the four-momentum transfer range 0.06<Q2<2.8 GeV2.
      Even at the lowest values of Q2, R remains nearly constant and does not disappear
      with decreasing Q2, as might be expected. We find a nearly identical behavior for
      hydrogen and deuterium.

PMID- 17501269
TI  - Origin of anomalous spectra of dynamic alignments observed in N2 and O2.
AB  - Recent pump-probe experiments with intense femtosecond laser pulses and diatomic
      molecules N2 and O2, have revealed the presence of Raman-forbidden anomalous
      series and lines in the Fourier spectrum of HHG (high harmonic generation)
      signals. A theoretical analysis of the problem is made by deriving a general
      expression of the angle dependent HHG operator that governs the dynamic alignment
      signals in linear molecules, and applying them to the experiments in N2 and O2. A
      unified interpretation of the origin of the observed Raman-allowed and the
      anomalous spectral features is given. The results are also used to estimate the
      molecular temperature in the experiments.

PMID- 17501270
TI  - Outstanding spin-orbit-activated interchannel coupling in the Cs and Ba 3d
      photoemission.
AB  - Partial 3d5/2 photoionization cross sections of atomic Cs and Ba as well as the
      asymmetry parameter beta of the angular distribution of the Cs 3d5/2
      photoelectrons were investigated near the threshold of the 3d3/2 channel at about
      750 eV and 800 eV, respectively. Strong electron correlations, in particular, the
      spin-orbit activated interchannel coupling between the 3d5/2 and 3d3/2 channels,
      govern the observed spectra. The most striking effect was found for beta5/2 of Cs
      with a dramatic increase from beta=1.0 to beta=1.5 in the energy region where the
      mixing between both channels causes a pronounced minimum in the partial 3d5/2
      cross section. This result indicates the decisive influence of the interference
      term on the asymmetry parameter beta with its dependence on the phase difference
      between the outgoing p and f waves.

PMID- 17501271
TI  - Laser-induced resonance shifts of single molecules self-coupled by a metallic
      surface.
AB  - The spectral properties of single molecules placed near a metallic surface are
      investigated at low temperatures. Because of the high quality factor of the
      optical resonance, a laser-induced shift of the molecular lines is evidenced for
      the first time. The shift dependence on the laser excitation intensity and on the
      dephasing rate of the transition dipole is studied. A simple theoretical model of
      a laser-driven molecule self-coupled by a mirror is developed to qualitatively
      interpret the observations.

PMID- 17501272
TI  - Plasmon-enhanced electron acceleration in intense laser metal-cluster
      interactions.
AB  - We have measured the energy and angular-resolved electron emission from medium
      sized silver clusters (N approximately 500-2000) exposed to dual laser pulses of
      moderate intensity (I approximately (10(13-14) W/cm2). When the second pulse
      excites the plasmon resonantly, we observe enhanced emission along the laser
      polarization axis. The asymmetry of the electron spectrum is strongly increasing
      with electron energy. Semiclassical simulations reveal the following mechanism:
      Electrons bound in highly excited states can leave, return to, and traverse the
      cluster. Those electrons that return at zero plasmon deflection and traverse the
      cluster during a favorable plasmon half-cycle can experience maximum acceleration
      by the evolving polarization field. As a result of these constraints energetic
      electrons are emitted in direction of the laser polarization axis in subcycle
      bursts.

PMID- 17501273
TI  - Quantum state-resolved probing of strong-field-ionized xenon atoms using
      femtosecond high-order harmonic transient absorption spectroscopy.
AB  - Femtosecond high-order harmonic transient absorption spectroscopy is used to
      resolve the complete |j,m quantum state distribution of Xe+ produced by optical
      strong-field ionization of Xe atoms at 800 nm. Probing at the Xe N4/5 edge yields
      a population distribution rhoj,|m| of
      rho3/2,1/2ratiorho1/2,1/2ratiorho3/2,3/2=75+/-6 :12+/-3 :13+/-6%. The result is
      compared to a tunnel ionization calculation with the inclusion of spin-orbit
      coupling, revealing nonadiabatic ionization behavior. The sub-50-fs time
      resolution paves the way for tabletop extreme ultraviolet absorption probing of
      ultrafast dynamics.

PMID- 17501274
TI  - Spatial extent of random laser modes.
AB  - We have experimentally studied the distribution of the spatial extent of modes
      and the crossover from essentially single-mode to distinctly multimode behavior
      inside a porous gallium phosphide random laser. This system serves as a paragon
      for random lasers due to its exemplary high index contrast. In the multimode
      regime, we observed mode competition. We have measured the distribution of
      spectral mode spacings in our emission spectra and found level repulsion that is
      well described by the Gaussian orthogonal ensemble of random-matrix theory.

PMID- 17501275
TI  - Lasing with resonant feedback in weakly scattering random systems.
AB  - Laser action in active random media in the weak scattering regime far from
      Anderson localization is investigated by coupling Maxwell's equations with the
      rate equations of a four-level atomic system. We report systematic lasing action
      with resonant feedback and show that the lasing modes mostly consist of traveling
      waves spatially extended over the whole system. Next we address the question of
      the origin of the feedback mechanism in such a system where no disorder-induced
      long-lived resonances are available, and present strong evidence that they
      correspond to the quasimodes of the passive system. This in turn provides an
      original way to access the spatial distribution of the quasimodes of a non
      Hermitian system.

PMID- 17501276
TI  - Measured thermal dissipation field in turbulent Rayleigh-Benard convection.
AB  - The time-averaged local thermal dissipation rate epsilonN(r) in turbulent
      convection is obtained from direct measurements of the temperature gradient
      vector in a cylindrical cell filled with water. It is found that epsilonN(r)
      contains two contributions. One is generated by thermal plumes, present mainly in
      the plume-dominated bulk region, and decreases with increasing Rayleigh number
      Ra. The other contribution comes from the mean temperature gradient, being
      concentrated in the thermal boundary layers, and increases with Ra. The
      experiment thus provides a new physical picture about the thermal dissipation
      field in turbulent convection.

PMID- 17501277
TI  - Uncovering the Lagrangian skeleton of turbulence.
AB  - We present a technique that uncovers the Lagrangian building blocks of
      turbulence, and apply this technique to a quasi-two-dimensional turbulent flow
      experiment. Our analysis identifies an intricate network of attracting and
      repelling material lines. This chaotic tangle, the Lagrangian skeleton of
      turbulence, shows a level of complexity found previously only in theoretical and
      numerical examples of strange attractors. We quantify the strength
      (hyperbolicity) of each material line in the skeleton and demonstrate
      dramatically different mixing properties in different parts of the tangle.

PMID- 17501278
TI  - Satellites in the inviscid breakup of bubbles.
AB  - In this Letter, we stress the essential role played by gas inertia in the breakup
      of gas bubbles. Our results reveal that, whenever the gas to liquid density ratio
      Lambda=rhog/rhol is different from zero, tiny satellite bubbles may be formed as
      a result of the large gas velocities that are reached close to pinch-off.
      Moreover, we provide a closed expression for the characteristic satellite
      diameter, which decreases when decreasing Lambda and which shows order of
      magnitude agreement with the micron-sized satellite bubbles observed
      experimentally.

PMID- 17501279
TI  - Structure of the wake of a magnetic obstacle.
AB  - We use a combination of numerical simulations and experiments to elucidate the
      structure of the flow of an electrically conducting fluid past a localized
      magnetic field, called magnetic obstacle. We demonstrate that the stationary flow
      pattern is considerably more complex than in the wake behind an ordinary body.
      The steady flow is shown to undergo two bifurcations (rather than one) and to
      involve up to six (rather than just two) vortices. We find that the first
      bifurcation leads to the formation of a pair of vortices within the region of
      magnetic field that we call inner magnetic vortices, whereas a second bifurcation
      gives rise to a pair of attached vortices that are linked to the inner vortices
      by connecting vortices.

PMID- 17501280
TI  - Observation of enhanced transformer ratio in collinear wakefield acceleration.
AB  - One approach to future high energy particle accelerators is based on the
      wakefield principle: a leading high-charge drive bunch is used to excite fields
      in an accelerating structure or plasma that in turn accelerates a trailing low
      charge witness bunch. The transformer ratio R is defined as the ratio of the
      maximum energy gain of the witness bunch to the maximum energy loss of the drive
      bunch. In general, R<2 for this configuration. A number of techniques have been
      proposed to overcome the transformer ratio limitation. We report here the first
      experimental study of the ramped bunch train (RBT) technique in a dielectric
      based accelerating structure. A single drive bunch was replaced by two bunches
      with charge ratio of 1:2.5 and a separation of 10.5 wavelengths of the
      fundamental mode. An average measured transformer ratio enhancement by a factor
      of 1.31 over the single drive bunch case was obtained.

PMID- 17501281
TI  - Lateral electron transport in high-intensity laser-irradiated foils diagnosed by
      ion emission.
AB  - An experimental investigation of lateral electron transport in thin metallic foil
      targets irradiated by ultraintense (>or=10(19) W/cm2) laser pulses is reported.
      Two-dimensional spatially resolved ion emission measurements are used to quantify
      electric-field generation resulting from electron transport. The measurement of
      large electric fields ( approximately 0.1 TV/m) millimeters from the laser focus
      reveals that lateral energy transport continues long after the laser pulse has
      decayed. Numerical simulations confirm a very strong enhancement of electron
      density and electric field at the edges of the target.

PMID- 17501282
TI  - Formation of collisionless high-beta plasmas by odd-parity rotating magnetic
      fields.
AB  - Odd-parity rotating magnetic fields (RMFo) applied to mirror-configuration
      plasmas have produced average electron energies exceeding 200 eV at line-averaged
      electron densities of approximately 10(12) cm-3. These plasmas, sustained for
      over 10(3)tauAlfven, have low Coulomb collisionality, vc* triple bond L/lambdaC
      approximately 10(-3), where lambdaC is the Coulomb scattering mean free path and
      L is the plasma's characteristic half length. Divertors allow reduction of the
      electron-neutral collision frequency to values where the RMFo coupling indicates
      full penetration of the RMFo to the major axis.

PMID- 17501265
TI  - Measurement of the pseudoscalar decay constant fDs using charm-tagged events in
      e+e- collisions at square root s=10.58 GeV.
AB  - Using 230.2 fb-1 of e+e- annihilation data collected with the BABAR detector at
      and near the peak of the Upsilon(4S) resonance, 489+/-55 events containing the
      pure leptonic decay Ds+-->micro;+numicro have been isolated in charm-tagged
      events. The ratio of partial widths Gamma(D+-->micro+numicro)/Gamma(Ds+-->phipi+)
      is measured to be 0.143+/-0.018+/-0.006 allowing a determination of the
      pseudoscalar decay constant fDs=(283+/-17+/-7+/-14) MeV. The errors are
      statistical, systematic, and from the Ds+-->phipi+ branching ratio, respectively.

PMID- 17501283
TI  - Non-newtonian viscosity of complex-plasma fluids.
AB  - Investigations of shear flows in three-dimensional complex-plasma fluids produced
      in a dc discharge were carried out. The shear was induced either by an
      inhomogeneous gas flow or by a laser beam. The viscosity of complex plasmas was
      measured over a broad range of shear rates, up to the hydrodynamic limit when the
      discreteness becomes important. Analysis of the measurements reveals non
      Newtonian behavior of complex plasmas accompanied by substantial shear thinning.

PMID- 17501284
TI  - Does the standard model of low-temperature glass dynamics describe a real glass?
AB  - We present the first experimental single-molecule (SM) spectroscopy study of the
      local dynamics in molecular glasses (frozen toluene and deuterated toluene weakly
      doped with a substituted terrylene) at T=2-30 K. Surprisingly, the dynamics does
      not follow the standard model of low-temperature glasses. An extra contribution
      to the dynamics was detected causing drifts and irreproducible jumps of the SM
      spectra. The isotope effects in the SM linewidth distribution and the density of
      states (boson peak) show that the fast dynamics at T=2 K is due to excitations of
      tunneling nature, whereas at T>7 K it is related to vibrations; H/D atoms are
      directly involved in both types of excitations.

PMID- 17501285
TI  - Subnanometer-scale measurements of the interaction of ultrafast soft x-ray free
      electron-laser pulses with matter.
AB  - At the recently built FLASH x-ray free-electron laser, we studied the
      reflectivity of Si/C multilayers with fluxes up to 3 x 10(14) W/cm2. Even though
      the nanostructures were ultimately completely destroyed, we found that they
      maintained their integrity and reflectance characteristics during the 25-fs-long
      pulse, with no evidence for any structural changes over lengths greater than 3 A.
      This experiment demonstrates that with intense ultrafast pulses, structural
      damage does not occur during the pulse, giving credence to the concept of
      diffraction imaging of single macromolecules.

PMID- 17501266
TI  - Measurement of the top-quark mass in all-hadronic decays in pp collisions at CDF
      II.
AB  - We present a measurement of the top-quark mass Mtop in the all-hadronic decay
      channel tt-->W+bW-b-->q1q2bq3q4b. The analysis is performed using 310 pb-1 of
      sqrt[s]=1.96 TeV pp[over ] collisions collected with the CDF II detector using a
      multijet trigger. The mass measurement is based on an event-by-event likelihood
      which depends on both the sample purity and the value of the top-quark mass,
      using 90 possible jet-to-parton assignments in the six-jet final state. The joint
      likelihood of 290 selected events yields a value of Mtop=177.1+/-4.9(stat)+/
      4.7(syst) GeV/c2.

PMID- 17501286
TI  - Pressure dependence of the radial breathing mode of carbon nanotubes: the effect
      of fluid adsorption.
AB  - The pressure dependence of shifts in the vibrational modes of individual carbon
      nanotubes is strongly affected by the nature of the pressure transmitting medium
      as a result of adsorption at the nanotube surface. The adsorbate is treated as an
      elastic shell which couples with the radial breathing mode (RBM) of the nanotube
      via van der Waal interactions. Using analytical methods as well as molecular
      simulation, we observe a low frequency breathing mode for the adsorbed fluid at
      approximately 50 cm-1, as well as diameter dependent upshifts in the RBM
      frequency with pressure, suggesting metallic nanotubes may wet more than
      semiconducting ones.

PMID- 17501287
TI  - Fano lineshape and phonon softening in single isolated metallic carbon nanotubes.
AB  - Evolution of G-band modes of single metallic carbon nanotubes with the Fermi
      level shift is examined by simultaneous Raman and electron transport studies.
      Narrow Lorentzian line shape and upshifted frequencies are observed near the van
      Hove singularities. However, all G modes soften and broaden at the band crossing
      point. The concurrent appearance of an asymmetric Fano line shape at this point
      indicates that phonon-continuum coupling is intrinsic to single metallic tubes.
      The apparent Lorentzian line shapes of as-synthesized metallic tubes are induced
      by O2 adsorption causing the Fermi level shift.

PMID- 17501288
TI  - Exact results for curvature-driven coarsening in two dimensions.
AB  - We consider the statistics of the areas enclosed by domain boundaries ("hulls")
      during the curvature-driven coarsening dynamics of a two-dimensional nonconserved
      scalar field from a disordered initial state. We show that the number of hulls
      per unit area that enclose an area greater than A has, for large time t, the
      scaling form Nh(A,t)=2c/(A+lambdat), demonstrating the validity of dynamical
      scaling in this system, where c=1/8pisquare root 3 is a universal constant.
      Domain areas (regions of aligned spins) have a similar distribution up to very
      large values of A/lambdat. Identical forms are obtained for coarsening from a
      critical initial state, but with c replaced by c/2.

PMID- 17501289
TI  - Origin of the failure of classical nucleation theory: incorrect description of
      the smallest clusters.
AB  - We carry out molecular Monte Carlo simulations of clusters in an imperfect vapor.
      We show that down to very small cluster sizes, classical nucleation theory built
      on the liquid drop model can be used very accurately to describe the work
      required to add a monomer to the cluster. However, the error made in modeling the
      smallest of clusters as liquid drops results in an erroneous absolute value for
      the cluster work of formation throughout the size range. We calculate factors
      needed to correct the cluster formation work given by the liquid drop model. The
      corrected work of formation results in nucleation rates in good agreement with
      recent nucleation experiments on argon and water.

PMID- 17501290
TI  - Spontaneous onion-structure formation from planar lamellar nuclei.
AB  - Nucleation and growth are a basic elementary process of ordering. The nucleation
      process is controlled by a competition between interfacial and bulk energy. Thus
      an ordered structure of a nucleus at its birth is not necessarily the most stable
      thermodynamically: Ostwald step rule. In addition to this, we found the
      topological transformation of nuclei from the most stable bulk structure (planar
      lamella) to a metastable one (onion) in a lyotropic liquid crystal. This
      indicates that the fate of nuclei of low-dimensional internal order can also be
      seriously affected by an additional competition between interfacial and elastic
      deformation energy.

PMID- 17501291
TI  - Anharmonic magnetic deformation of self-assembled molecular nanocapsules.
AB  - High magnetic fields were used to deform spherical nanocapsules, self-assembled
      from bolaamphiphilic sexithiophene molecules. At low fields the deformation-
      measured through linear birefringence-scales quadratically with the capsule
      radius and with the magnetic field strength. These data confirm a long standing
      theoretical prediction [W. Helfrich, Phys. Lett. A 43, 409 (1973)10.1016/0375
      9601(73)90396-4], and permit the determination of the bending rigidity of the
      capsules as (2.6+/-0.8) x 10(-21) J. At high fields, an enhanced rigidity is
      found which cannot be explained within the Helfrich model. We propose a complete
      form of the free energy functional that accounts for this behavior, and allows
      discussion of the formation and stability of nanocapsules in solution.

PMID- 17501292
TI  - Mechanism for nanotube formation from self-bending nanofilms driven by atomic
      scale surface-stress imbalance.
AB  - We demonstrate, by theoretical analysis and molecular dynamics simulation, a
      mechanism for fabricating nanotubes by self-bending of nanofilms under intrinsic
      surface-stress imbalance due to surface reconstruction. A freestanding Si
      nanofilm may spontaneously bend itself into a nanotube without external stress
      load, and a bilayer SiGe nanofilm may bend into a nanotube with Ge as the inner
      layer, opposite of the normal bending configuration defined by misfit strain.
      Such rolled-up nanotubes can accommodate a high level of strain, even beyond the
      magnitude of lattice mismatch, greatly modifying the tube electronic and
      optoelectronic properties.

PMID- 17501293
TI  - Generalized neural-network representation of high-dimensional potential-energy
      surfaces.
AB  - The accurate description of chemical processes often requires the use of
      computationally demanding methods like density-functional theory (DFT), making
      long simulations of large systems unfeasible. In this Letter we introduce a new
      kind of neural-network representation of DFT potential-energy surfaces, which
      provides the energy and forces as a function of all atomic positions in systems
      of arbitrary size and is several orders of magnitude faster than DFT. The high
      accuracy of the method is demonstrated for bulk silicon and compared with
      empirical potentials and DFT. The method is general and can be applied to all
      types of periodic and nonperiodic systems.

PMID- 17501294
TI  - Electron mass in dilute nitrides and its anomalous dependence on hydrostatic
      pressure.
AB  - The dependence of the electron mass on hydrostatic pressure P in N-diluted GaAs1
      xNx (x=0.10% and 0.21%) is investigated by magnetophotoluminescence. Exceedingly
      large fluctuations (up to 60%/kbar) in the electron mass with increasing P are
      found. These originate from a pressure-driven tuning of the hybridization degree
      between the conduction band minimum and specific nitrogen-related states. Present
      results suggest a hierarchy between different nitrogen complexes as regards the
      extent of the perturbation these complexes exert on the electronic properties of
      the GaAs host.

PMID- 17501295
TI  - Evidence for an oxygen diffusion model for the electric pulse induced resistance
      change effect in transition-metal oxides.
AB  - Electric-pulse induced resistance hysteresis switching loops for Pr0.7Ca0.3MnO3
      perovskite oxide films were found to exhibit an additional sharp "shuttle tail"
      peak around the negative pulse maximum for films deposited in an oxygen-deficient
      ambient. The resistance relaxation in time of this "shuttle tail" peak as well as
      resistance relaxation in the transition regions of the resistance hysteresis loop
      show evidence of oxygen diffusion under electric pulsing, and support a proposed
      oxygen diffusion model with oxygen vacancy pileup at the metal electrode
      interface region as the active process for the nonvolatile resistance switching
      effect in transition-metal oxides.

PMID- 17501296
TI  - Possible coexistence of local itinerancy and global localization in a quasi-one
      dimensional conductor.
AB  - In the chain compound PrBa2Cu4O8 localization appears simultaneously with a
      dimensional crossover in the electronic ground state when the scattering rate in
      the chains exceeds the hopping rate between the chains. Here we report the
      discovery of a large, transverse magnetoresistance in PrBa2Cu4O8 in the localized
      regime. This result suggests a novel form of localization whereby electrons
      retain their metallic (quasi-one-dimensional) character over a microscopic length
      scale despite the fact that, macroscopically, they exhibit localized (one
      dimensional) behavior.

PMID- 17501297
TI  - Giant current-driven domain wall mobility in (Ga,Mn)As.
AB  - We study theoretically hole current-driven domain wall dynamics in (Ga,Mn)As. We
      show that the spin-orbit coupling causes significant hole reflection at the
      domain wall, even in the adiabatic limit when the wall is much thicker than the
      Fermi wavelength, resulting in spin accumulation and mistracking between current
      carrying spins and the domain wall magnetization. This increases the out-of-plane
      nonadiabatic spin-transfer torque and consequently the current-driven domain wall
      mobility by 3 to 4 orders of magnitude. Trends and magnitude of the calculated
      domain wall current mobilities agree with experimental findings.

PMID- 17501298
TI  - Electrical spin injection and threshold reduction in a semiconductor laser.
AB  - A spin-polarized vertical-cavity surface-emitting laser is demonstrated with
      electrical spin injection from an Fe/Al0.1Ga0.9As Schottky tunnel barrier. Laser
      operation with a spin-polarized current results in a maximum threshold current
      reduction of 11% and degree of circular polarization of 23% at 50 K. A cavity
      spin polarization of 16.8% is estimated from spin-dependent rate equation
      analysis of the observed threshold reduction.

PMID- 17501299
TI  - Superconducting states of pure and doped graphene.
AB  - We study the superconducting phases of the two-dimensional honeycomb lattice of
      graphene. We find two spin singlet pairing states; s wave and an exotic p+ip that
      is possible because of the special structure of the honeycomb lattice. At half
      filling, the p+ip phase is gapless and superconductivity is a hidden order. We
      discuss the possibility of a superconducting state in metal coated graphene.

PMID- 17501300
TI  - Evidence for a single hydrogen molecule connected by an atomic chain.
AB  - Stable, single-molecule conducting-bridge configurations are typically identified
      from peak structures in a conductance histogram. In previous work on Pt with H2
      at cryogenic temperatures it has been shown that a peak near 1G0 identifies a
      single-molecule Pt-H2-Pt bridge. The histogram shows an additional structure with
      lower conductance that has not been identified. Here, we show that it is likely
      due to a hydrogen decorated Pt chain in contact with the H2 molecular bridge.

PMID- 17501301
TI  - Experimental observation of quantum confinement in the conduction band of CdSe
      quantum dots.
AB  - X-ray absorption spectroscopy has been used to characterize the evolution in the
      conduction band (CB) density of states of CdSe quantum dots (QDs) as a function
      of particle size. We have unambiguously witnessed the CdSe QD CB minimum (CBM)
      shift to higher energy with decreasing particle size, consistent with quantum
      confinement effects, and have directly compared our results with recent
      theoretical calculations. At the smallest particle size, evidence for a pinning
      of the CBM is presented. Our observations can be explained by considering a size
      dependent change in the angular-momentum-resolved states at the CBM.

PMID- 17501302
TI  - Doping of monatomic Cu chains with single Co atoms.
AB  - Close-packed Co-Cu chains of various length and composition were assembled from
      single Co and Cu atoms on Cu(111) by atom manipulation in a low-temperature
      scanning tunneling microscope. Local spectroscopy reveals significant electronic
      Co-Cu coupling leading to confined quantum states delocalized along the
      heteroatomic chain. Composite Co-Cu chains provide a model case in which the
      quantum state of an atomic-scale host structure can be tuned by the controlled
      incorporation of foreign atoms.

PMID- 17501303
TI  - Resonance fluorescence in transport through quantum dots: noise properties.
AB  - We study a two-level quantum dot embedded in a phonon bath and irradiated by a
      time-dependent ac field, and develop a method that allows us to extract
      simultaneously the full counting statistics of the electronic tunneling and
      relaxation (by phononic emission) events as well as their correlation. We find
      that the quantum noise of both the transmitted electrons and the emitted phonons
      can be controlled by the manipulation of external parameters such as the driving
      field intensity or the bias voltage.

PMID- 17501305
TI  - Superconducting state of the organic conductor (TMTSF)2ClO4.
AB  - (TMTSF)2ClO4 is a quasi-one-dimensional organic conductor and superconductor with
      Tc=1.4 K, and one of at least two Bechgaard salts observed to have upper critical
      fields far exceeding the paramagnetic limit. Nevertheless, the 77Se NMR Knight
      shift at low fields reveals a decrease in spin susceptibility chi(s) consistent
      with singlet spin pairing. The field dependence of the spin-lattice relaxation
      rate at 100 mK exhibits a sharp crossover (or phase transition) at a field Hs
      approximately 15 kOe, to a regime where chi(s) is close to the normal state
      value, even though Hc2>> Hs.

PMID- 17501304
TI  - High-energy scale revival and giant kink in the dispersion of a cuprate
      superconductor.
AB  - In the present photoemission study of a cuprate superconductor
      Bi1.74Pb0.38Sr1.88CuO6+delta, we discovered a large scale dispersion of the
      lowest band, which unexpectedly follows the band structure calculation very well.
      Similar behavior observed in blue bronze and the Mott insulator Ca2CuO2Cl2
      suggests that the origin of hopping-dominated dispersion in an overdoped cuprate
      might be quite complicated. A giant kink in the dispersion is observed, and the
      complete self-energy containing all interaction information is extracted for a
      doped cuprate. These results recovered significant missing pieces in our current
      understanding of the electronic structure of cuprates.

PMID- 17501306
TI  - Continuous measurement of the energy eigenstates of a nanomechanical resonator
      without a nondemolition probe.
AB  - We show that it is possible to perform a continuous measurement that continually
      projects a nanoresonator into its energy eigenstates by employing a linear
      coupling with a two-state system. This technique makes it possible to perform a
      measurement that exposes the quantum nature of the resonator by coupling it to a
      Cooper-pair box and a superconducting transmission line resonator.

PMID- 17501307
TI  - Magnetic instability regions in patterned structures: influence of element shape
      on magnetization reversal dynamics.
AB  - We report a time-resolved imaging study of the influence of shape on magnetic
      instabilities in patterned magnetic structures. We find that in rectangular
      structures magnetization reversal initiates at the ends and interior
      simultaneously, while in structures with tapered ends the reversal begins in the
      middle of the structures and spreads out to the ends. The degree of tapering is
      important for both the switching field and the time required for full reversal. A
      model based on the concept of local instability regions yields good agreement
      with the observed location of the reversal onsets.

PMID- 17501308
TI  - Large magnetostriction and negative thermal expansion in the frustrated
      antiferromagnet ZnCr2Se4.
AB  - A detailed investigation of ZnCr2Se4 is presented which is dominated by strong
      ferromagnetic exchange but orders antiferromagnetically at TN=21 K. Specific heat
      and thermal expansion exhibit sharp first-order anomalies at the
      antiferromagnetic transition. TN is shifted to lower temperatures by external
      magnetic fields and finally is fully suppressed by a field of 65 kOe. The
      relative length change DeltaL/L(T) is unusually large and exhibits negative
      thermal expansion alpha below 75 K down to TN indicating strong frustration of
      the lattice. Magnetostriction DeltaL/L(H) reveals large values comparable to
      giant magnetostrictive materials. These results point to a spin-driven origin of
      the structural instability at TN explained in terms of competing ferromagnetic
      and antiferromagnetic exchange interactions.

PMID- 17501309
TI  - Electric control of spin helicity in a magnetic ferroelectric.
AB  - Magnetic ferroelectrics or multiferroics, which are currently extensively
      explored, may provide a good arena to realize a novel magnetoelectric function.
      Here we demonstrate the genuine electric control of the spiral magnetic structure
      in one such magnetic ferroelectric, TbMnO3. A spin-polarized neutron scattering
      experiment clearly shows that the spin helicity, clockwise or counterclockwise,
      is controlled by the direction of spontaneous polarization and hence by the
      polarity of the small electric field applied on cooling.

PMID- 17501310
TI  - Numerical renormalization group for continuum one-dimensional systems.
AB  - We present a renormalization group (RG) procedure which works naturally on a wide
      class of interacting one-dimension models based on perturbed (possibly strongly)
      continuum conformal and integrable models. This procedure integrates Wilson's
      numerical renormalization group with Zamolodchikov's truncated conformal spectrum
      approach. The key to the method is that such theories provide a set of completely
      understood eigenstates for which matrix elements can be exactly computed. In this
      procedure the RG flow of physical observables can be studied both numerically and
      analytically. To demonstrate the approach, we study the spectrum of a pair of
      coupled quantum Ising chains and correlation functions in a single quantum Ising
      chain in the presence of a magnetic field.

PMID- 17501311
TI  - Analysis of dynamics of excitation and dephasing of plasmon resonance modes in
      nanoparticles.
AB  - A novel theoretical approach to the dynamics analysis of excitation and dephasing
      of plasmon modes in nanoparticles is presented. This approach is based on the
      biorthogonal plasmon mode expansion, and it leads to the predictions of time
      dynamics of excitation of specific plasmon modes as well as their steady state
      amplitude and their decay. Temporal characteristics of plasmon modes in
      nanoparticles are expressed in terms of their shapes, permittivity dispersion
      relations, and excitation conditions. In the case of the Drude model, analytical
      expressions for time-dynamics of plasmon modes are obtained.

PMID- 17501312
TI  - Dielectric response of aligned semiconducting single-wall nanotubes.
AB  - We report measurements of the full intrinsic optical anisotropy of isolated
      single-wall carbon nanotubes (SWNTs). By combining absorption spectroscopy with
      transmission ellipsometry and polarization-dependent resonant Raman scattering,
      we obtain the real and imaginary parts of the SWNT permittivity from aligned
      semiconducting SWNTs dispersed in stretched polymer films. Our results are in
      agreement with theoretical predictions, highlighting the limited polarizability
      of excitons in a quasi-1D system.

PMID- 17501313
TI  - Semisoft nematic elastomers and nematics in crossed electric and magnetic fields.
AB  - Nematic elastomers with a locked-in anisotropy direction exhibit semisoft elastic
      response characterized by a plateau in the stress-strain curve in which stress
      does not change with strain. We calculate the global phase diagram for a minimal
      model, which is equivalent to one describing a nematic in crossed electric and
      magnetic fields, and show that semisoft behavior is associated with a broken
      symmetry biaxial phase and that it persists well into the supercritical regime.
      We also consider generalizations beyond the minimal model and find similar
      results.

PMID- 17501314
TI  - Irrational mode locking in quasiperiodic systems.
AB  - A model for ac-driven systems, based on the Tang-Wiesenfeld-Bak-Coppersmith
      Littlewood automaton for an elastic medium, exhibits mode-locked steps with
      frequencies that are irrational multiples of the drive frequency, when the
      pinning is spatially quasiperiodic. Detailed numerical evidence is presented for
      the large-system-size convergence of such a mode-locked step. The irrational mode
      locking is stable to small thermal noise and weak disorder. Continuous-time
      models with irrational mode locking and possible experimental realizations are
      discussed.

PMID- 17501315
TI  - Diverse population-bursting modes of adapting spiking neurons.
AB  - We study the dynamics of a noisy network of spiking neurons with spike-frequency
      adaptation (SFA), using a mean-field approach, in terms of a two-dimensional
      Fokker-Planck equation for the membrane potential of the neurons and the calcium
      concentration gating SFA. The long time scales of SFA allow us to use an
      adiabatic approximation and to describe the network as an effective nonlinear two
      dimensional system. The phase diagram is computed for varying levels of SFA and
      synaptic coupling. Two different population-bursting regimes emerge, depending on
      the level of SFA in networks with noisy emission rate, due to the finite number
      of neurons.

PMID- 17501316
TI  - Ising-like model for protein mechanical unfolding.
AB  - The mechanical unfolding of proteins is studied by extending the Wako-Saito-Munoz
      Eaton model. This model is generalized by including an external force, and its
      thermodynamics turns out to be exactly solvable. We consider two molecules, the
      27th immunoglobulin domain of titin and protein PIN1. We determine equilibrium
      force-extension curves for the titin and study the mechanical unfolding of this
      molecule, finding good agreement with experiments. By using an extended form of
      the Jarzynski equality, we compute the free energy landscape of the PIN1 as a
      function of the molecule length.

PMID- 17501317
TI  - Patterning colloidal films via evaporative lithography.
AB  - We investigate evaporative lithography as a route for patterning colloidal films.
      Films are dried beneath a mask that induces periodic variations between regions
      of free and hindered evaporation. Direct imaging reveals that particles segregate
      laterally within the film, as fluid and entrained particles migrate towards
      regions of higher evaporative flux. The films exhibit remarkable pattern
      formation that can be regulated by tuning the initial suspension composition,
      separation distance between the mask and underlying film, and mask geometry.

PMID- 17501318
TI  - Comment on "Improved experimental limit on the electric dipole moment of the
      neutron".

PMID- 17501320
TI  - Comment on "Chiral suppression of scalar-glueball decay".

PMID- 17501322
TI  - Statistics of critical points of Gaussian fields on large-dimensional spaces.
AB  - We calculate the average number of critical points of a Gaussian field on a high
      dimensional space as a function of their energy and their index. Our results give
      a complete picture of the organization of critical points and are of relevance to
      glassy and disordered systems and landscape scenarios coming from the anthropic
      approach to string theory.

PMID- 17501323
TI  - Dynamical instability of a rotating dipolar Bose-Einstein condensate.
AB  - We analyze the hydrodynamic solutions for a dilute Bose-Einstein condensate with
      long-range dipolar interactions in a rotating, elliptical harmonic trap. The
      static solutions and their regimes of dynamical instability vary nontrivially
      with the strength of the dipolar interactions. We comprehensively map out this
      behavior, and, in particular, examine the experimental routes toward unstable
      dynamics, which, in analogy to conventional condensates, may lead to vortex
      lattice formation.

PMID- 17501324
TI  - Sufficiency criterion for the validity of the adiabatic approximation.
AB  - We examine the quantitative condition which has been widely used as a criterion
      for the adiabatic approximation but was recently found insufficient. Our results
      indicate that the usual quantitative condition is sufficient for a special class
      of quantum mechanical systems. For general systems, it may not be sufficient, but
      it, along with additional conditions, is sufficient. The usual quantitative
      condition and the additional conditions constitute a general criterion for the
      validity of the adiabatic approximation, which is applicable to all N-dimensional
      quantum systems. Moreover, we illustrate the use of the general quantitative
      criterion in some physical models.

PMID- 17501325
TI  - Correlation functions of the one-dimensional attractive Bose gas.
AB  - The zero-temperature correlation functions of the one-dimensional attractive Bose
      gas with a delta-function interaction are calculated analytically for any value
      of the interaction parameter and number of particles, directly from the
      integrability of the model. We point out a number of interesting features,
      including zero recoil energy for a large number of particles, analogous to the
      Mossbauer effect.

PMID- 17501326
TI  - Scheme for demonstration of fractional statistics of anyons in an exactly
      solvable model.
AB  - We propose a scheme to demonstrate fractional statistics of anyons in an exactly
      solvable lattice model proposed by Kitaev that involves four-body interactions.
      The required many-body ground state, as well as the anyon excitations and their
      braiding operations, can be conveniently realized through dynamic laser
      manipulation of cold atoms in an optical lattice. Because of the perfect
      localization of anyons in this model, we show that a quantum circuit with only
      six qubits is enough for demonstration of the basic braiding statistics of
      anyons. This opens up the immediate possibility of proof-of-principle experiments
      with trapped ions, photons, or nuclear magnetic resonance systems.

PMID- 17501327
TI  - Minimal set of local measurements and classical communication for two-mode
      Gaussian state entanglement quantification.
AB  - We develop the minimal requirements for the complete entanglement quantification
      of an arbitrary two-mode bipartite Gaussian state via local measurements and a
      classical communication channel. The minimal set of measurements is presented as
      a reconstruction protocol of local covariance matrices and no previous knowledge
      of the state is required but its Gaussian character. The protocol becomes very
      simple mostly when dealing with Gaussian states transformed to its standard form,
      since photocounting or intensity measurements define the whole set of entangled
      states. In addition, conditional on some prior information, the protocol is also
      useful for a complete global state reconstruction.

PMID- 17501328
TI  - Sequential quantum cloning.
AB  - Not all unitary operations upon a set of qubits can be implemented by sequential
      interactions between each qubit and an ancillary system. We analyze the specific
      case of sequential quantum cloning, 1-->M, and prove that the minimal dimension D
      of the ancilla grows linearly with the number of clones M. In particular, we
      obtain D=2M for symmetric universal quantum cloning and D=M+1 for symmetric phase
      covariant cloning. Furthermore, we provide a recipe for the required ancilla
      qubit interactions in each step of the sequential procedure for both cases.

PMID- 17501329
TI  - Entropy production and time asymmetry in nonequilibrium fluctuations.
AB  - The time-reversal symmetry of nonequilibrium fluctuations is experimentally
      investigated in two out-of-equilibrium systems: namely, a Brownian particle in a
      trap moving at constant speed and an electric circuit with an imposed mean
      current. The dynamical randomness of their nonequilibrium fluctuations is
      characterized in terms of the standard and time-reversed entropies per unit time
      of dynamical systems theory. We present experimental results showing that their
      difference equals the thermodynamic entropy production in units of Boltzmann's
      constant.

PMID- 17501330
TI  - Exploring the thermodynamic limit of Hamiltonian models: convergence to the
      Vlasov equation.
AB  - We here discuss the emergence of quasistationary states (QSS), a universal
      feature of systems with long-range interactions. With reference to the
      Hamiltonian mean-field model, numerical simulations are performed based on both
      the original N-body setting and the continuum Vlasov model which is supposed to
      hold in the thermodynamic limit. A detailed comparison unambiguously demonstrates
      that the Vlasov-wave system provides the correct framework to address the study
      of QSS. Further, analytical calculations based on Lynden-Bell's theory of violent
      relaxation are shown to result in accurate predictions. Finally, in specific
      regions of parameters space, Vlasov numerical solutions are shown to be affected
      by small scale fluctuations, a finding that points to the need for novel schemes
      able to account for particle correlations.

PMID- 17501331
TI  - Chemically powered nanodimers.
AB  - Self-propelled motion of a chemically powered nanodimer is discussed. The
      nanodimer comprises two linked spheres, one of which has equal interactions with
      A and B solvent species but catalyzes the reaction A-->B. The other sphere is not
      chemically active but interacts differently with the two species. The
      nonequilibrium concentration gradient generated at the catalytic end, in
      conjunction with the force difference at the noncatalytic end, leads to directed
      motion. The model mimics features of experimentally studied synthetic nanorod
      motion. Particle-based simulations and analytical estimates of the velocity
      provide insight into the nature of nanomotor directed motion.

PMID- 17501332
TI  - Laboratory test of Newton's second law for small accelerations.
AB  - We have tested the proportionality of force and acceleration in Newton's second
      law, F=ma, in the limit of small forces and accelerations. Our tests reach well
      below the acceleration scales relevant to understanding several current
      astrophysical puzzles such as the flatness of galactic rotation curves, the
      Pioneer anomaly, and the Hubble acceleration. We find good agreement with
      Newton's second law at accelerations as small as 5 x 10(-14) m/s(2).

PMID- 17501333
TI  - An all-optical trap for a gram-scale mirror.
AB  - We report on a stable optical trap suitable for a macroscopic mirror, wherein the
      dynamics of the mirror are fully dominated by radiation pressure. The technique
      employs two frequency-offset laser fields to simultaneously create a stiff
      optical restoring force and a viscous optical damping force. We show how these
      forces may be used to optically trap a free mass without introducing thermal
      noise, and we demonstrate the technique experimentally with a 1 g mirror. The
      observed optical spring has an inferred Young's modulus of 1.2 TPa, 20% stiffer
      than diamond. The trap is intrinsically cold and reaches an effective temperature
      of 0.8 K, limited by technical noise in our apparatus.

PMID- 17501334
TI  - Analysis of rotation curves in the framework of the gravitational suppression
      model.
AB  - We present an analysis of suitable rotation curves (RCs) of eight galaxies, aimed
      at checking the consistency and universality of the gravitational suppression
      (GraS) hypothesis, a phenomenological model for a new interaction between dark
      matter and baryons. Motivated by the puzzle of the core versus cusp distribution
      of dark matter in the center of halos, this hypothesis claims to reconcile the
      predictions from N-body Lambda cold dark matter simulations with kinematic
      observations. The GraS model improves the kinematic fitting residuals, but the
      mass parameters are unphysical and put the theory in difficulty.

PMID- 17501337
TI  - Gauge mediation simplified.
AB  - Gauge mediation of supersymmetry breaking is drastically simplified using generic
      superpotentials without U(1)R symmetry by allowing metastable vacua.

PMID- 17501339
TI  - Core-corona separation in ultrarelativistic heavy ion collisions.
AB  - Simple geometrical considerations show that the collision zone in high energy
      nuclear collisions may be divided into a central part ("core"), with high energy
      densities, and a peripheral part ("corona"), with smaller energy densities, more
      like in pp or pA collisions. We present calculations that allow us to separate
      these two contributions, and which show that the corona contribution is quite
      small (but not negligible) for central collisions, but gets increasingly
      important with decreasing centrality. We will discuss consequences concerning
      results obtained in heavy ion collisions at the BNL Relativistic Heavy Ion
      Collider and CERN Super Proton Synchrotron.

PMID- 17501338
TI  - Compton-scattering cross section on the proton at high momentum transfer.
AB  - Cross-section values for Compton scattering on the proton were measured at 25
      kinematic settings over the range s=5-11 and -t=2-7 GeV2 with a statistical
      accuracy of a few percent. The scaling power for the s dependence of the cross
      section at fixed center-of-mass angle was found to be 8.0+/-0.2, strongly
      inconsistent with the prediction of perturbative QCD. The observed cross-section
      values are in fair agreement with the calculations using the handbag mechanism,
      in which the external photons couple to a single quark.

PMID- 17501340
TI  - Nuclear-matter modification of decay widths in the phi-->e+e- and phi-->K+K-
      channels.
AB  - The invariant mass spectra of phi-->K+K- are measured in 12 GeV p+A reactions in
      order to search for the in-medium modification of phi mesons. The observed K+K-
      spectra are well reproduced by the relativistic Breit-Wigner function with a
      combinatorial background shape in three betagamma regions between 1.0 and 3.5.
      The nuclear mass number dependence of the yields of the K+K- decay channel is
      compared to the simultaneously measured e+e- decay channel for carbon and copper
      targets. We parameterize the production yields as sigma(A)=sigma0Aalpha and
      obtain alphaphi-->K+K- -alphaphi-->e+e- to be 0.14+/-0.12. Limits are obtained
      for the partial decay widths of the phi mesons in nuclear matter.

PMID- 17501341
TI  - Relating breakup and incomplete fusion of weakly bound nuclei through a classical
      trajectory model with stochastic breakup.
AB  - A classical dynamical model that treats breakup stochastically is presented for
      low energy reactions of weakly bound nuclei. The three-dimensional model allows a
      consistent calculation of breakup, incomplete, and complete fusion cross
      sections. The model is assessed by comparing the breakup observables with
      continuum discretized coupled-channel quantum mechanical predictions, which are
      found to be in reasonable agreement. Through the model, it is demonstrated that
      the breakup probability of the projectile as a function of its distance from the
      target is of primary importance for understanding complete and incomplete fusion
      at energies near the Coulomb barrier.

PMID- 17501342
TI  - Triple differential cross sections for the double photoionization of H2.
AB  - Triple differential cross sections arising from the break up of the H2 molecule
      by a single photon are presented. The time-dependent close-coupling technique is
      used to calculate differential cross sections for various geometries. Excellent
      agreement is found between current work and recent exterior complex-scaling
      calculations, confirming, for the first time, the absolute magnitude of the
      triple differential cross sections. Our calculations also compare favorably with
      recent synchrotron light source measurements.

PMID- 17501343
TI  - Cancellation of the collisional frequency shift in caesium fountain clocks.
AB  - We have observed that the collisional frequency shift in primary caesium fountain
      clocks varies with the clock state population composition and, in particular, is
      zero for a given fraction of the |F=4,mF=0) atoms, depending on the initial cloud
      parameters. We present a theoretical model explaining our observations. The
      possibility of the collisional shift cancellation implies an improvement in the
      performance of caesium fountain standards and a simplification in their
      operation.

PMID- 17501344
TI  - Strongly correlated two-photon transport in a one-dimensional waveguide coupled
      to a two-level system.
AB  - We show that two-photon transport is strongly correlated in one-dimensional
      waveguide coupled to a two-level system. The exact S matrix is constructed using
      a generalized Bethe-ansatz technique. We show that the scattering eigenstates of
      this system include a two-photon bound state that passes through the two-level
      system as a composite single particle. Also, the two-level system can induce
      effective attractive or repulsive interactions in space for photons. This general
      procedure can be applied to the Anderson model as well.

PMID- 17501345
TI  - Solving the Kadanoff-Baym equations for inhomogeneous systems: application to
      atoms and molecules.
AB  - We implement time propagation of the nonequilibrium Green function for atoms and
      molecules by solving the Kadanoff-Baym equations within a conserving self-energy
      approximation. We here demonstrate the usefulness of time propagation for
      calculating spectral functions and for describing the correlated electron
      dynamics in a nonperturbative electric field. We also demonstrate the use of time
      propagation as a method for calculating charge-neutral excitation energies,
      equivalent to highly advanced solutions of the Bethe-Salpeter equation.

PMID- 17501346
TI  - Wide-bandwidth, tunable, multiple-pulse-width optical delays using slow light in
      cesium vapor.
AB  - We demonstrate an all-optical delay line in hot cesium vapor that tunably delays
      275 ps input pulses up to 6.8 ns and 740 input ps pulses up to 59 ns (group index
      of approximately 200) with little pulse distortion. The delay is made tunable
      with a fast reconfiguration time (hundreds of ns) by optically pumping out of the
      atomic ground states.

PMID- 17501347
TI  - Correcting low-frequency noise with continuous measurement.
AB  - Low-frequency noise presents a serious source of decoherence in solid-state
      qubits. When combined with a continuous weak measurement of the eigenstates, low
      frequency noise induces a second-order relaxation between the qubit states. Here,
      we show that the relaxation provides a unique approach to calibrate the low
      frequency noise in the time domain. By encoding one qubit with two physical
      qubits that are alternatively calibrated, quantum-logic gates with high fidelity
      can be performed.

PMID- 17501348
TI  - Measuring photon antibunching from continuous variable sideband squeezing.
AB  - We present a technique for measuring the second-order coherence function
      g(2)(tau) of light using a Hanbury Brown-Twiss intensity interferometer modified
      for homodyne detection. The experiment was performed entirely in the continuous
      variable regime at the sideband frequency of a bright carrier field. We used the
      setup to characterize g(2)(tau) for thermal and coherent states and investigated
      its immunity to optical loss. We measured g(2)(tau) of a displaced-squeezed state
      and found a best antibunching statistic of g(2)(0)=0.11+/-0.18.

PMID- 17501349
TI  - Directional emission from weakly eccentric resonators.
AB  - It is shown that when a circular resonator is deformed in a nonintegrable way, a
      symmetry breaking of escaping rays occurs which can dramatically modulate the
      outgoing wave even for small perturbations. The underlying mechanism does not
      occur in integrable models for which the ray families can be computed exactly and
      is described in this Letter on the basis of canonical perturbation theory.
      Emission from deformed resonators is currently of immense practical interest in
      the context of whispering-gallery optical resonances of dielectric cavities, and
      the approach outlined here promises simple analytical characterizations in the
      important case of small deformations.

PMID- 17501335
TI  - Measurement of the charge asymmetry in semileptonic Bs0 decays.
AB  - We have performed the first direct measurement of the time-integrated flavor
      untagged charge asymmetry in semileptonic Bs0 decays ASLs,unt by comparing the
      decay rate of Bs0-->micro+Ds-nuX, where Ds- -->phipi- and phi-->K+K-, with the
      charge-conjugate Bs0 decay rate. This sample was selected from 1.3 fb-1 of data
      collected by the D0 experiment in run II of the Fermilab Tevatron collider. We
      obtain ASLs,unt=[1.23+/-0.97(stat)+/-0.17(syst)]x10(-2). Assuming that
      Deltam(s)/Gamma(s)>>1, this result can be translated into a measurement of the CP
      violating phase in Bs0 mixing: DeltaGamma(s)/Deltam(s)tanphi(s)=[2.45+/
      1.93(stat)+/-0.35(syst)]x10(-2).

PMID- 17501350
TI  - Near-field analysis of surface waves launched at nanoslit apertures.
AB  - With the aim of analyzing the properties of the waves that are scattered by
      nanoslits on metallic surfaces, we provide a direct observation of the near-field
      in a slit-doublet experiment at optical wavelengths. We show that two distinct
      waves are involved: a surface plasmon polariton and another wave with a free
      space character. From the recorded data, we have extracted the amplitudes and
      phases of these waves, their damping characteristic lengths and their relative
      weights as a function of the separation distance from the slit. The analysis is
      fully supported by a quantitative agreement with vector-theory computational
      results.

PMID- 17501336
TI  - Branching fraction measurements of B+-->rho+gamma, B0-->rho0gamma, and B0-
      >omegagamma.
AB  - We present a study of the decays B+-->rho+gamma, B0-->rho0gamma, and B0-
      >omegagamma. The analysis is based on data containing 347 x 10(6) BB[over ]
      events recorded with the BABAR detector at the PEP-II asymmetric B factory. We
      measure the branching fractions B(B+-->rho+)gamma)=(1.10_(-0.33)(+0.37)+/
      0.09)x10(-6) and B(B0-->rho0gamma)=(0.79(-0.20)(+0.22)+/-0.06)x10(-6), and set a
      90% C.L. upper limit B(B0-->omegagamma)<0.78 x 10(-6). We also measure the
      isospin-averaged branching fraction B(B-->(rho/omega)gamma)=(1.25(-0.24)(+0.25)+/
      0.09)x10(-6), from which we determine |Vtd/Vts|=0.200(-0.020)(+0.021)+/-0.015,
      where the first uncertainty is experimental and the second is theoretical.

PMID- 17501352
TI  - Destructive interference during high harmonic generation in mixed gases.
AB  - We report on the first experimental evidence of the destructive and constructive
      interference of high harmonics generated in a mixed gas of He and Ne, which
      facilitates the coherent control of high harmonic generation. Theoretically, we
      develop an analytical model of high harmonic generation in mixed gases and
      succeed in reproducing the experimental results and deriving the optimization
      conditions for the process. The observed interference modulation is attributed to
      the difference between the phases of the intrinsically chirped harmonic pulses
      from He and Ne, which leads to a novel method for broadband measurement of the
      harmonic phases and for observing the underlying attosecond electron dynamics.

PMID- 17501351
TI  - Excitability in a quantum dot semiconductor laser with optical injection.
AB  - We experimentally analyze the dynamics of a quantum dot semiconductor laser
      operating under optical injection. We observe the appearance of single- and
      double-pulse excitability at one boundary of the locking region. Theoretical
      considerations show that these pulses are related to a saddle-node bifurcation on
      a limit cycle as in the Adler equation. The double pulses are related to a period
      doubling bifurcation and occur on the same homoclinic curve as the single pulses.

PMID- 17501353
TI  - All-optical phase-change memory in a single gallium nanoparticle.
AB  - We report on the first demonstration of a quaternary-logical resonatorless
      optical memory element with information encoded in the structural phase of a
      single 80 nm gallium nanoparticle. The size of the memory element is comparable
      with bits in next-generation hard disks, and radically smaller than previously
      suggested memories exploiting optical resonators. Furthermore, the energy
      required for switching the nanoparticle is an order of magnitude less than needed
      in DVD, DVR, or hard disk technologies.

PMID- 17501354
TI  - Enhanced coupling of subterahertz radiation with semiconductor periodic slot
      arrays.
AB  - In this work, a theoretical study of the coupling of TM polarized subterahertz
      (THz) radiation with periodic semiconductor rectangular slot arrays was
      conducted, using InSb as an example. Simulation results showed that the structure
      with 4-12 microm thickness provides over a 20-30-fold increase in the electric
      field at slot edges in a nanosize region ( approximately 500 nm). The enhancement
      of the THz electromagnetic field extends across the slots and reaches peak values
      at the edges due to discontinuity effects. Because of the strong local
      electromagnetic field enhancement, the structure can potentially be used for the
      development of novel biophotonic sensors, leading to improved detection
      sensitivity.

PMID- 17501355
TI  - Synchronization of mutually coupled chaotic lasers in the presence of a shutter.
AB  - Two mutually coupled chaotic diode lasers exhibit stable isochronal
      synchronization in the presence of self-feedback. When the mutual communication
      between the lasers is discontinued by a shutter and the two uncoupled lasers are
      subject to self-feedback only, the desynchronization time is found to scale as
      Adtau, where Ad>1 and tau corresponds to the optical distance between the lasers.
      Prior to synchronization, when the two lasers are uncorrelated and the shutter
      between them is opened, the synchronization time is found to be much shorter,
      though still proportional to tau. As a consequence of these results, the
      synchronization is not significantly altered if the shutter is opened or closed
      faster than the desynchronization time. Experiments in which the coupling between
      two chaotic-synchronized diode lasers is modulated with an electro-optic shutter
      are found to be consistent with the results of numerical simulations.

PMID- 17501356
TI  - Observation of intermittency in wave turbulence.
AB  - We report the observation of intermittency in gravity-capillary wave turbulence
      on the surface of mercury. We measure the temporal fluctuations of surface wave
      amplitude at a given location. We show that the shape of the probability density
      function of the local slope increments of the surface waves strongly changes
      across the time scales. The related structure functions and the flatness are
      found to be power laws of the time scale on more than one decade. The exponents
      of these power laws increase nonlinearly with the order of the structure
      function. All these observations show the intermittent nature of the increments
      of the local slope in wave turbulence. We discuss the possible origin of this
      intermittency.

PMID- 17501357
TI  - Scaling law for a subcritical transition in plane Poiseuille flow.
AB  - The scaling law for the threshold amplitude of perturbations to initiate a
      transition in subcritical plane Poiseuille flow as a function of the Reynolds
      number is demonstrated experimentally. The disturbances are introduced through an
      almost streamwise independent slot drilled at the bottom wall of a horizontal air
      channel flow. Following the two stages of transition, linear transient growth and
      nonlinear secondary instability, it is found that the normalized critical
      injection rate (v0) scales with the Reynolds number (R) as v0 approximately R
      3/2. This scaling law agrees with the theoretical predictions of Chapman [J.
      Fluid Mech. 451, 34 (2002).].

PMID- 17501359
TI  - Shock ignition of thermonuclear fuel with high areal density.
AB  - A novel method by C. Zhou and R. Betti [Bull. Am. Phys. Soc. 50, 140 (2005)] to
      assemble and ignite thermonuclear fuel is presented. Massive cryogenic shells are
      first imploded by direct laser light with a low implosion velocity and on a low
      adiabat leading to fuel assemblies with large areal densities. The assembled fuel
      is ignited from a central hot spot heated by the collision of a spherically
      convergent ignitor shock and the return shock. The resulting fuel assembly
      features a hot-spot pressure greater than the surrounding dense fuel pressure.
      Such a nonisobaric assembly requires a lower energy threshold for ignition than
      the conventional isobaric one. The ignitor shock can be launched by a spike in
      the laser power or by particle beams. The thermonuclear gain can be significantly
      larger than in conventional isobaric ignition for equal driver energy.

PMID- 17501358
TI  - High-efficiency volume reflection of an ultrarelativistic proton beam with a bent
      silicon crystal.
AB  - The volume reflection phenomenon was detected while investigating 400 GeV proton
      interactions with bent silicon crystals in the external beam H8 of the CERN Super
      Proton Synchrotron. Such a process was observed for a wide interval of crystal
      orientations relative to the beam axis, and its efficiency exceeds 95%, thereby
      surpassing any previously observed value. These observations suggest new
      perspectives for the manipulation of high-energy beams, e.g., for collimation and
      extraction in new-generation hadron colliders, such as the CERN Large Hadron
      Collider.

PMID- 17501360
TI  - Fine structure of a laser-plasma filament in air.
AB  - The ability to select and stabilize a single filament during propagation of an
      ultrashort high-intensity laser pulse in air makes it possible to examine the
      longitudinal structure of the plasma channel left in its wake. We present
      detailed measurements of plasma density variations along laser propagation. Over
      the length of the filament, electron density variations of 3 orders of magnitude
      are measured. They display evidence of a meter-long postionization range, along
      which a self-guided structure is observed coupled with a low plasma density,
      corresponding to approximately 3 orders of magnitude decrease from the peak
      density level.

PMID- 17501361
TI  - Measuring functional renormalization group fixed-point functions for pinned
      manifolds.
AB  - Exact numerical minimization of interface energies is used to test the functional
      renormalization group analysis for interfaces pinned by quenched disorder. The
      fixed-point function R(u) (the correlator of the coarse-grained disorder) is
      computed. In dimensions D=d+1, a linear cusp in R''(u) is confirmed for random
      bond (d=1, 2, 3), random field (d=0, 2, 3), and periodic (d=2, 3) disorders. The
      functional shocks that lead to this cusp are seen. Small, but significant,
      deviations from the 1-loop calculation are compared to 2-loop corrections and
      chaos is measured.

PMID- 17501362
TI  - Absorbing states and elastic interfaces in random media: two equivalent
      descriptions of self-organized criticality.
AB  - We elucidate a long-standing puzzle about the nonequilibrium universality classes
      describing self-organized criticality in sandpile models. We show that depinning
      transitions of linear interfaces in random media and absorbing phase transitions
      (with a conserved nondiffusive field) are two equivalent languages to describe
      sandpile criticality. This is so despite the fact that local roughening
      properties can be radically different in the two pictures, as explained here.
      Experimental implications of our work as well as promising paths for future
      theoretical investigations are also discussed.

PMID- 17501363
TI  - Epitaxy, truncations, and overhangs in palladium nanoclusters adsorbed on
      MgO(001).
AB  - The structure of Pd clusters adsorbed on MgO(001) is determined by a combination
      of global-optimization methods using semiempirical potentials and density
      functional calculations. The transition to fcc clusters with (001) epitaxy is
      shown to take place in the size range 10<or=N<or=15 atoms. Truncations of
      vertices and basal corners in fcc epitaxial clusters proceed in parallel, while
      overhangs are already formed at small sizes, below 30 atoms.

PMID- 17501364
TI  - Adatom-adatom interaction mediated by an underlying surface phase transition.
AB  - Low temperature scanning tunneling microscopy measurements on the adsorption of
      single Pb adatoms on Si(111)-(square root 3 x square root 3)-Pb surfaces reveal
      the vertical displacement patterns induced on the substrate by these Pb adatoms
      as well as a novel adatom-adatom interaction. The origin of both can be traced
      back to the (square root 3 x square root 3)<-->(3 x 3) phase transition taking
      place at lower temperatures. A Landau-like approach explains the displacement
      patterns as due to the corresponding order parameter and shows that the vicinity
      of a surface phase transition gives rise to a nonmonotonic adatom-adatom
      interaction.

PMID- 17501365
TI  - Capillary origami: spontaneous wrapping of a droplet with an elastic sheet.
AB  - The interaction between elasticity and capillarity is used to produce three
      dimensional structures through the wrapping of a liquid droplet by a planar
      sheet. The final encapsulated 3D shape is controlled by tailoring the initial
      geometry of the flat membrane. Balancing interfacial energy with elastic bending
      energy provides a critical length scale below which encapsulation cannot occur,
      which is verified experimentally. This length is found to depend on the thickness
      as h3/2, a scaling favorable to miniaturization which suggests a new way of mass
      production of 3D micro- or nanoscale objects.

PMID- 17501366
TI  - Nuclear spin ferromagnetic phase transition in an interacting two dimensional
      electron gas.
AB  - Electrons in a two-dimensional semiconducting heterostructure interact with
      nuclear spins via the hyperfine interaction. Using a a Kondo lattice formulation
      of the electron-nuclear-spin interaction, we show that the nuclear-spin system
      within an interacting two-dimensional electron gas undergoes a ferromagnetic
      phase transition at finite temperatures. We find that electron-electron
      interactions and non-Fermi liquid behavior substantially enhance the nuclear-spin
      Curie temperature into the mK range with decreasing electron density.

PMID- 17501367
TI  - Coexistence of strongly mixed-valence and heavy-fermion character in SmOs4Sb12
      studied by soft- and hard-X-ray spectroscopy.
AB  - Sm-based heavy-fermion compound SmOs4Sb12 has been investigated by soft x-ray
      (hnu=1070-1600 eV) and hard x-ray (HX; hnu=7932 eV) spectroscopy. The HX
      photoemission spectroscopy clearly demonstrates that the strongly mixed-valence
      state and the heavy-fermion state coexist in the bulk. It is found that the Sm
      valence decreases below 100 K, indicating that the Kondo coherence develops with
      approaching the proposed Kondo temperature. Our theoretical analyses suggest that
      the origin of the coexistence in SmOs4Sb12 is the coincidence of two conditions,
      namely, (i) the energy difference between Sm divalent and trivalent states is
      very small and (ii) the hybridization between Sm 4f and conduction electrons is
      weak.

PMID- 17501368
TI  - Room-temperature reversible spin Hall effect.
AB  - Reversible spin Hall effect comprising the direct and inverse spin Hall effects
      was electrically detected at room temperature. A platinum wire with a strong spin
      orbit interaction is used not only as a spin current absorber but also as a spin
      current source in the specially designed lateral structure. The obtained spin
      Hall conductivities are 2.4 x 10(4) (Omega m)(-1) at room temperature, 10(4)
      times larger than the previously reported values of semiconductor systems. Spin
      Hall conductivities obtained from both the direct and inverse spin Hall effects
      are experimentally confirmed to be the same, demonstrating the Onsager reciprocal
      relations between spin and charge currents.

PMID- 17501369
TI  - Randomness-induced XY ordering in a graphene quantum hall ferromagnet.
AB  - Valley-polarized quantum Hall states in graphene are described by a Heisenberg
      O(3) ferromagnet model, with the ordering type controlled by the strength and the
      sign of the valley anisotropy. A mechanism resulting from electron coupling to
      the strain-induced gauge field, giving a leading contribution to the anisotropy,
      is described in terms of an effective random magnetic field aligned with the
      ferromagnet z axis. We argue that such a random field stabilizes the XY
      ferromagnet state, which is a coherent equal-weight mixture of the K and K'
      valley states. The implications such as the Berezinskii-Kosterlitz-Thouless
      ordering transition and topological defects with half-integer charge are
      discussed.

PMID- 17501370
TI  - Multifractality and conformal invariance at 2D metal-insulator transition in the
      spin-orbit symmetry class.
AB  - We study the multifractality (MF) of critical wave functions at boundaries and
      corners at the metal-insulator transition (MIT) for noninteracting electrons in
      the two-dimensional (2D) spin-orbit (symplectic) universality class. We find that
      the MF exponents near a boundary are different from those in the bulk. The
      exponents at a corner are found to be directly related to those at a straight
      boundary through a relation arising from conformal invariance. This provides
      direct numerical evidence for conformal invariance at the 2D spin-orbit MIT. The
      presence of boundaries modifies the MF of the whole sample even in the
      thermodynamic limit.

PMID- 17501371
TI  - Absorption in the fractional quantum Hall regime: trion dichroism and spin
      polarization.
AB  - We present measurements of optical interband absorption in the fractional quantum
      Hall regime in a GaAs quantum well in the range 0<nu<or=1. We investigate the
      mechanism of singlet trion absorption, and show that its circular dichroism can
      be used as a probe of the spin polarization of the ground state of the two
      dimensional electron system (2DES). We find that at nu<or=1/3 the 2DES is fully
      spin polarized. Increasing the filling factor results in a gradual
      depolarization, with a sharp minimum in the dichroism near nu=2/3. We find that
      in the range 0.5<or=nu<0.85 the 2DES remains partially polarized for the broad
      range of magnetic fields from 2.75 to 11 T. This is consistent with the presence
      of a mixture of polarized and depolarized regions.

PMID- 17501372
TI  - Influence of coupling between junctions on breakpoint current in intrinsic
      Josephson junctions.
AB  - We study theoretically the current-voltage characteristics of intrinsic Josephson
      junctions in high-Tc superconductors. An oscillation of the breakpoint current on
      the outermost branch as a function of coupling alpha and dissipation beta
      parameters is found. We explain this oscillation as a result of the creation of
      longitudinal plasma waves at the breakpoint with different wave numbers. We
      demonstrate the commensurability effect and predict a group behavior of the
      current-voltage characteristics for the stacks with a different number of
      junctions. A method to determine the wave number of longitudinal plasma waves
      from alpha and beta dependence of the breakpoint current is suggested. We model
      the alpha and beta dependence of the breakpoint current and obtain good agreement
      with the results of the simulation.

PMID- 17501373
TI  - Dual character of the electronic structure of YBa2Cu4O8: the conduction bands of
      CuO2 planes and CuO chains.
AB  - We use microprobe angle-resolved photoemission spectroscopy (microARPES) to
      separately investigate the electronic properties of CuO2 planes and CuO chains in
      the high temperature superconductor, YBa2Cu4O8. For the CuO2 planes, a two
      dimensional (2D) electronic structure is observed and, in contrast to
      Bi2Sr2CaCu2O8+delta, the bilayer splitting is almost isotropic and 50% larger,
      which strongly suggests that bilayer splitting has no direct effect on the
      superconducting properties. In addition, the scattering rate for the bonding band
      is about 1.5 times stronger than the antibonding band and is independent of
      momentum. For the CuO chains, the electronic structure is quasi-one-dimensional
      and consists of a conduction and insulating band. Finally, we find that the
      conduction electrons are well confined within the planes and chains with a
      nontrivial hybridization.

PMID- 17501374
TI  - Detection of valley polarization in graphene by a superconducting contact.
AB  - Because the valleys in the band structure of graphene are related by time
      reversal symmetry, electrons from one valley are reflected as holes from the
      other valley at the junction with a superconductor. We show how this Andreev
      reflection can be used to detect the valley polarization of edge states produced
      by a magnetic field. In the absence of intervalley relaxation, the conductance
      GNS=(2e2/h)(1-cosTheta) of the junction on the lowest quantum Hall plateau is
      entirely determined by the angle Theta between the valley isospins of the edge
      states approaching and leaving the superconductor. If the superconductor covers a
      single edge, Theta=0 and no current can enter the superconductor. A measurement
      of GNS then determines the intervalley relaxation time.

PMID- 17501375
TI  - Spin freezing in geometrically frustrated antiferromagnets with weak disorder.
AB  - We investigate the consequences for geometrically frustrated antiferromagnets of
      weak disorder in the strength of exchange interactions. Taking as a model the
      classical Heisenberg antiferromagnet with nearest neighbor exchange on the
      pyrochlore lattice, we examine low-temperature behavior. We show that spatial
      modulation of exchange generates long-range effective interactions within the
      extensively degenerate ground states of the clean system. Using Monte Carlo
      simulations, we find a spin glass transition at a temperature set by the disorder
      strength. Disorder of this type, which is generated by random strains in the
      presence of magnetoelastic coupling, may account for the spin freezing observed
      in many geometrically frustrated magnets.

PMID- 17501376
TI  - Symmetry of multiferroicity in a frustrated magnet TbMn2O5.
AB  - Based on measurements of soft-x-ray magnetic scattering and symmetry
      considerations, we demonstrate that the magnetoelectric effect in TbMn2O5 arises
      from an internal field determined by S-->q--> x S-->-q--> with S-->q--> being the
      magnetization at modulation vector q-->, whereas the magnetoelastic effect in the
      exchange energy governs the response to external electric fields. Our results set
      fundamental symmetry constraints on the microscopic mechanism of multiferroicity
      in frustrated magnets.

PMID- 17501377
TI  - Spin-wave eigenmodes of a saturated magnetic square at different precession
      angles.
AB  - Using low-loss dielectric magnetic films in combination with space-resolved
      Brillouin light scattering spectroscopy we have studied nonlinear modification of
      eigenmode spatial distributions in saturated magnetic squares. We have found
      that, as the angle of magnetization precession increases, the eigenmode spatial
      distributions experience significant qualitative changes due to a nonlinear
      coupling between forming them standing spin waves. We show that the found
      nonlinear eigenmodes cannot be described by means of the linear theoretical
      approach even qualitatively.

PMID- 17501378
TI  - Dynamically induced frustration as a route to a quantum spin ice state in
      Tb2Ti2O7 via virtual crystal field excitations and quantum many-body effects.
AB  - The Tb2Ti2O7 pyrochlore magnetic material is attracting much attention for its
      spin liquid state, failing to develop long-range order down to 50 mK despite a
      Curie-Weiss temperature thetaCW approximately -14 K. In this Letter we
      reinvestigate the theoretical description of this material by considering a
      quantum model of independent tetrahedra to describe its low-temperature
      properties. The naturally tuned proximity of this system near a Neel to spin ice
      phase boundary allows for a resurgence of quantum fluctuation effects that lead
      to an important renormalization of its effective low-energy spin Hamiltonian. As
      a result, Tb2Ti2O7 is argued to be a quantum spin ice. We put forward an
      experimental test of this proposal using neutron scattering on a single crystal.

PMID- 17501379
TI  - Intergranular magnetoresistance in Sr2FeMoO6 from a magnetic tunnel barrier
      mechanism across grain boundaries.
AB  - We present magnetization (M) and magnetoresistance (MR) data for a series of
      Sr2FeMoO6 samples with independent control on antisite defect and grain-boundary
      densities, which reveal several unexpected features, including a novel switching
      like behavior of MR with M. These, in conjunction with model calculations,
      establish that the MR in Sr2FeMoO6 is dominantly controlled by a new mechanism,
      derived from the magnetic polarization of grain-boundary regions acting like spin
      valves, leading to behavior qualitatively different from that usually encountered
      in tunneling MR. We show that a simple and useful experimental signature for the
      presence of this spin-valve-type MR (SVMR) is a wider hysteresis in MR compared
      to that in M.

PMID- 17501380
TI  - Kondo interactions and magnetic correlations in CePt2 nanocrystals.
AB  - The evolution of the Kondo effect and antiferromagnetic (AF) correlations with
      size reduction in CePt2 nanoparticles (3.1-26 nm) is studied by analysis of the
      temperature-dependent specific heat and magnetic susceptibility. The AF
      correlations diminish with size reduction. The Kondo effect predominates at small
      particle size with trivalent, small Kondo temperature (TK) magnetic regions
      coexisting with strongly mixed-valent, large TK nonmagnetic regions. We discuss
      the role of structural disorder, background density of states and the electronic
      quantum size effect on the results.

PMID- 17501381
TI  - Prediction of strong dichroism induced by x rays carrying orbital momentum.
AB  - We predict the presence of strong dichroic effects induced by x-ray beams
      carrying orbital angular momentum (OAM). Taking the difference between spectra
      obtained with positive and negative OAM states allows the separation of
      quadrupolar from dipolar transitions at, e.g., the transition-metal K edges,
      enabling the study of the unoccupied states in the absence of strong core-hole
      effects. We study the dependence of OAM-induced x-ray dichroism on different
      polarization vectors and derive sum rules relating the integrated intensity to
      ground-state hole densities. Calculations of spectral line shapes for cuprates,
      manganites, and ruthenates confirm the strong OAM-induced dichroism and indicate
      the potential of this new spectroscopy in the fields of orbital physics and
      magnetism.

PMID- 17501382
TI  - Anomalous absorption line in the magneto-optical response of graphene.
AB  - The intensity as well as position in energy of the absorption lines in the
      infrared conductivity of graphene, both exhibit features that are directly
      related to the Dirac nature of its quasiparticles. We show that the evolution of
      the pattern of absorption lines as the chemical potential is varied encodes the
      information about the presence of the anomalous lowest Landau level. The first
      absorption line related to this level always appears with full intensity or is
      entirely missing, while all other lines disappear in two steps. We demonstrate
      that if a gap develops, the main absorption line splits into two provided that
      the chemical potential is greater than or equal to the gap.

PMID- 17501383
TI  - Experimental observation of left-handed behavior in an array of standard
      dielectric resonators.
AB  - We demonstrate that by utilizing displacement currents in simple dielectric
      resonators instead of conduction currents in metallic split-ring resonators and
      by additionally exciting the proper modes, left-handed properties can be observed
      in an array of high dielectric resonators. Theoretical analysis and experimental
      measurements show that the modes, as well as the subwavelength resonance, play an
      important role in the origin of the left-handed properties. The proposed
      implementation of a left-handed metamaterial, based on a purely dielectric
      configuration, opens the possibility of realizing media at terahertz frequencies
      since scaling issues and losses, two major drawbacks of metal-based structures,
      are avoided.

PMID- 17501384
TI  - Optimal control of quantum rings by terahertz laser pulses.
AB  - Complete control of single-electron states in a two-dimensional semiconductor
      quantum-ring model is established, opening a path into coherent laser-driven
      single-gate qubits. The control scheme is developed in the framework of optimal
      control theory for laser pulses of two-component polarization. In terms of pulse
      lengths and target-state occupations, the scheme is shown to be superior to
      conventional control methods that exploit Rabi oscillations generated by uniform
      circularly polarized pulses. Current-carrying states in a quantum ring can be
      used to manipulate a two-level subsystem at the ring center. Combining our
      results, we propose a realistic approach to construct a laser-driven single-gate
      qubit that has switching times in the terahertz regime.

PMID- 17501385
TI  - Colloidal interactions and transport in nematic liquid crystals.
AB  - We describe a new nematic liquid-crystal colloid system which is characterized by
      both charge stabilization of the particles and an interaction force. We estimate
      the effective charge of the particles by electrophoretic measurements and find
      that in such systems the director anchoring energy W is very low and the
      particles have little director distortion around them. The interaction force is
      created by producing a radial distribution of the nematic order parameter around
      a locally isotropic region created by ir laser heating. We theoretically describe
      this as being due to the induced flexoelectric polarization, the quadrupolar
      symmetry of which provides the required long-range force acting on charged
      particles.

PMID- 17501386
TI  - Unfolding of proteins and long transient conformations detected by single
      nanopore recording.
AB  - We study the electrophoretic blockades due to entries of partially unfolded
      proteins into a nanopore as a function of the concentration of the denaturing
      agent. Short and long pore blockades are observed by electrical detection. Short
      blockades are due to the passage of completely unfolded proteins, their frequency
      increases as the concentration of the denaturing agent increases, following a
      sigmoidal denaturation curve. Long blockades reveal partially folded
      conformations. Their duration increases as the proteins are more folded. The
      observation of a Vogel-Fulcher law suggests a glassy behavior.

PMID- 17501387
TI  - Concentration dependence of the collective dynamics of swimming bacteria.
AB  - At concentrations near the maximum allowed by steric repulsion, swimming bacteria
      form a dynamical state exhibiting extended spatiotemporal coherence. The viscous
      fluid into which locomotive energy of individual microorganisms is transferred
      also carries interactions that drive the coherence. The concentration dependence
      of correlations in the collective state is probed here with a novel technique
      that herds bacteria into condensed populations of adjustable concentration. For
      the particular thin-film geometry employed, the correlation lengths vary smoothly
      and monotonically through the transition from individual to collective behavior.

PMID- 17501388
TI  - Stretching of homopolymeric RNA reveals single-stranded helices and base
      stacking.
AB  - We have found strong supporting evidence for the helical structures of single
      stranded nucleic acids by stretching individual molecules of polyadenylic acid
      [poly(A)] and polycytidylic acid [poly(C)]. Analyzing the force versus extension
      data using a two-state elastic model in which random-coil domains alternate with
      rigid helical domains allows one to extract the thermodynamic and structural
      properties. In addition, it also yields moderate to low cooperativity of the
      helix-coil transition for poly(A) and poly(C), respectively.

PMID- 17501389
TI  - Thermodynamically stable pickering emulsions.
AB  - We show that under appropriate conditions, mixtures of oil, water, and
      nanoparticles form thermodynamically stable oil-in-water emulsions with
      monodisperse droplet diameters in the range of 30-150 nm. This observation
      challenges current wisdom that so-called Pickering emulsions are at most
      metastable and points to a new class of mesoscopic equilibrium structures.
      Thermodynamic stability is demonstrated by the spontaneous evolution of binary
      droplet mixtures towards one intermediate size distribution. Equilibrium
      interfacial curvature due to an asymmetric charge distribution induced by
      adsorbed colloids explains the growth of emulsion droplets upon salt addition.
      Moreover, the existence of a minimal radius of curvature with a concomitant
      expulsion of excess oil is in close analogy with microemulsions.

PMID- 17501390
TI  - Symmetry breaking of in-plane order in confined copolymer mesophases.
AB  - Packing of spherical-domain block copolymer mesophases confined to a thin film is
      investigated as a function of the number of layers n. We find an abrupt
      transition from hexagonal to orthorhombic in-plane ordering of domains when n is
      increased from 4 to 5. As n increases further (up to 23 in this study), the
      symmetry of the orthorhombic phase asymptotically approaches that of the body
      centered cubic (110) plane. These results are interpreted in terms of the
      energetics of competing packings in the bulk and at the film interfaces. Detailed
      structural and thermodynamic properties are obtained with self-consistent field
      theory.

PMID- 17501391
TI  - Basin entropy in Boolean network ensembles.
AB  - The information processing capacity of a complex dynamical system is reflected in
      the partitioning of its state space into disjoint basins of attraction, with
      state trajectories in each basin flowing towards their corresponding attractor.
      We introduce a novel network parameter, the basin entropy, as a measure of the
      complexity of information that such a system is capable of storing. By studying
      ensembles of random Boolean networks, we find that the basin entropy scales with
      system size only in critical regimes, suggesting that the informationally optimal
      partition of the state space is achieved when the system is operating at the
      critical boundary between the ordered and disordered phases.

PMID- 17501392
TI  - Impact of non-Poissonian activity patterns on spreading processes.
AB  - Halting a computer or biological virus outbreak requires a detailed understanding
      of the timing of the interactions between susceptible and infected individuals.
      While current spreading models assume that users interact uniformly in time,
      following a Poisson process, a series of recent measurements indicates that the
      intercontact time distribution is heavy tailed, corresponding to a temporally
      inhomogeneous bursty contact process. Here we show that the non-Poisson nature of
      the contact dynamics results in prevalence decay times significantly larger than
      predicted by the standard Poisson process based models. Our predictions are in
      agreement with the detailed time resolved prevalence data of computer viruses,
      which, according to virus bulletins, show a decay time close to a year, in
      contrast with the 1 day decay predicted by the standard Poisson process based
      models.

PMID- 17501393
TI  - Comment on "Rontgen quantum phase shift: a semiclassical local electrodynamical
      effect?".

PMID- 17501395
TI  - Optimal stochastic enhancement of photoionization.
AB  - The effect of noise on the nonlinear photoionization of an atom due to a
      femtosecond pulse is investigated in the framework of the stochastic Schrodinger
      equation. A modest amount of white noise results in an enhancement of the net
      ionization yield by several orders of magnitude, giving rise to a form of quantum
      stochastic resonance. We demonstrate that this effect is preserved if the white
      noise is replaced by broadband chaotic light.

PMID- 17501396
TI  - Optimal quantum estimation of loss in bosonic channels.
AB  - We address the estimation of the loss parameter of a bosonic channel probed by
      Gaussian signals. We derive the ultimate quantum bound with precision and show
      that no improvement may be obtained by having access to the environmental degrees
      of freedom. We find that, for small losses, the variance of the optimal estimator
      is proportional to the loss parameter itself, a result that represents a
      qualitative improvement over the shot-noise limit. An observable based on the
      symmetric logarithmic derivative is obtained, which attains the ultimate bound
      and may be implemented using Gaussian operations and photon counting.

PMID- 17501397
TI  - Polarized Fermi condensates with unequal masses: tuning the tricritical point.
AB  - We consider a two-component atomic Fermi gas within a mean-field, single-channel
      model, where both the mass and population of each component are unequal. We show
      that the tricritical point at zero temperature evolves smoothly from the BEC to
      BCS side of the resonance as a function of mass ratio r. We find that the
      interior gap state proposed by Liu and Wilczek is always unstable to phase
      separation, while the breached pair state with one Fermi surface for the excess
      fermions exhibits differences in its density of states and pair correlation
      functions depending on which side of the resonance it lies. Finally, we show
      that, when r greater, similar 3.95, the finite-temperature phase diagram of
      trapped gases at unitarity becomes topologically distinct from the equal mass
      system.

PMID- 17501398
TI  - Impossibility of the counterfactual computation for all possible outcomes.
AB  - A recent proposal for counterfactual computation [O. Hosten et al. Nature
      (London) 439, 949 (2006) is analyzed. It is argued that the method does not
      provide counterfactual computation for all possible outcomes. The explanation
      involves a novel paradoxical feature of pre- and postselected quantum particles:
      The particle can reach a certain location without being on the path that leads to
      this location.

PMID- 17501399
TI  - Quantum quenches in a spinor condensate.
AB  - We discuss the ordering of a spin-1 condensate when quenched from its
      paramagnetic phase to its ferromagnetic phase by reducing the magnetic field. We
      first elucidate the nature of the equilibrium quantum phase transition. Quenching
      rapidly through this transition reveals XY ordering either at a specific wave
      vector, or the "light-cone" correlations familiar from relativistic theories,
      depending on the end point of the quench. For a quench proceeding at a finite
      rate the ordering scale is governed by the Kibble-Zurek mechanism. The creation
      of vortices through growth of the magnetization fluctuations is also discussed.
      The long-time dynamics again depends on the end point, conserving the order
      parameter in a zero field, but not at a finite field, with differing exponents
      for the coarsening of magnetic order. The results are discussed in the light of a
      recent experiment by Sadler et al.

PMID- 17501400
TI  - Color superfluidity and "baryon" formation in ultracold fermions.
AB  - We study fermionic atoms of three different internal quantum states (colors) in
      an optical lattice, which are interacting through attractive on site
      interactions, U<0. Using a variational calculation for equal color densities and
      small couplings, |U|<|UC|, a color superfluid state emerges with a tendency to
      domain formation. For |U|>|UC|, triplets of atoms with different colors form
      singlet fermions (trions). These phases are the analogies of the color
      superconducting and baryonic phases in QCD. In ultracold fermions, this
      transition is found to be of second order. Our results demonstrate that quantum
      simulations with ultracold gases may shed light on outstanding problems in
      quantum field theory.

PMID- 17501401
TI  - Finite de Finetti theorem for infinite-dimensional systems.
AB  - We formulate and prove a de Finetti representation theorem for finitely
      exchangeable states of a quantum system consisting of k infinite-dimensional
      subsystems. The theorem is valid for states that can be written as the partial
      trace of a pure state |Psi/Psi| chosen from a family of subsets {Cn} of the full
      symmetric subspace for n subsystems. We show that such states become arbitrarily
      close to mixtures of pure power states as n increases. We give a second
      equivalent characterization of the family {Cn}.

PMID- 17501402
TI  - Quasienergy anholonomy and its application to adiabatic quantum state
      manipulation.
AB  - The parametric dependence of a quantum map under the influence of a rank-1
      perturbation is investigated. While the Floquet operator of the map and its
      spectrum have a common period with respect to the perturbation strength lambda,
      we show an example in which none of the quasienergies nor the eigenvectors obey
      the same period: After a periodic increment of lambda, the quasienergy arrives at
      the nearest higher one, instead of the initial one, exhibiting an anholonomy,
      which governs another anholonomy of the eigenvectors. An application to quantum
      state manipulations is outlined.

PMID- 17501403
TI  - Uniaxial and biaxial spin nematic phases induced by quantum fluctuations.
AB  - It is shown that zero point quantum fluctuations completely lift the accidental
      continuous degeneracy that is found in mean field analysis of quantum spin
      nematic phases of hyperfine spin-2 cold atoms. The result is two distinct ground
      states which have higher symmetries: a uniaxial spin nematic and a biaxial spin
      nematic with dihedral symmetry Dih4. There is a novel first-order quantum phase
      transition between the two phases as atomic scattering lengths are varied. We
      find that the ground state of 87Rb atoms should be a uniaxial spin nematic. We
      note that the energy barrier between the phases could be observable in dynamical
      experiments.

PMID- 17501404
TI  - Interacting anyons in topological quantum liquids: the golden chain.
AB  - We discuss generalizations of quantum spin Hamiltonians using anyonic degrees of
      freedom. The simplest model for interacting anyons energetically favors
      neighboring anyons to fuse into the trivial ("identity") channel, similar to the
      quantum Heisenberg model favoring neighboring spins to form spin singlets.
      Numerical simulations of a chain of Fibonacci anyons show that the model is
      critical with a dynamical critical exponent z=1, and described by a two
      dimensional (2D) conformal field theory with central charge c=7/10. An exact
      mapping of the anyonic chain onto the 2D tricritical Ising model is given using
      the restricted-solid-on-solid representation of the Temperley-Lieb algebra. The
      gaplessness of the chain is shown to have topological origin.

PMID- 17501405
TI  - Discriminating States: the quantum Chernoff bound.
AB  - We consider the problem of discriminating two different quantum states in the
      setting of asymptotically many copies, and determine the minimal probability of
      error. This leads to the identification of the quantum Chernoff bound, thereby
      solving a long-standing open problem. The bound reduces to the classical Chernoff
      bound when the quantum states under consideration commute. The quantum Chernoff
      bound is the natural symmetric distance measure between quantum states because of
      its clear operational meaning and because it does not seem to share some of the
      undesirable features of other distance measures.

PMID- 17501406
TI  - Topological computation without braiding.
AB  - We show that universal quantum computation can be performed within the ground
      state of a topologically ordered quantum system, which is a naturally protected
      quantum memory. In particular, we show how this can be achieved using brane-net
      condensates in 3-colexes. The universal set of gates is implemented without
      selective addressing of physical qubits and, being fully topologically protected,
      it does not rely on quasiparticle excitations or their braiding.

PMID- 17501407
TI  - Casimir-force-driven ratchets.
AB  - We explore the nonlinear dynamics of two parallel periodically patterned metal
      surfaces that are coupled by the zero-point fluctuations of the electromagnetic
      field between them. The resulting Casimir force generates for asymmetric patterns
      with a time periodically driven surface-to-surface distance a ratchet effect,
      allowing for directed lateral motion of the surfaces in sizable parameter ranges.
      It is crucial to take into account inertia effects and hence chaotic dynamics
      which are described by Langevin dynamics. Multiple velocity reversals occur as a
      function of driving, mean surface distance, and effective damping. These
      transport properties are shown to be stable against weak ambient noise.

PMID- 17501408
TI  - Unified TeV scale picture of baryogenesis and dark matter.
AB  - We present a simple extension of the minimal supersymmetric standard model which
      provides a unified picture of cosmological baryon asymmetry and dark matter. Our
      model introduces a gauge singlet field N and a color triplet field X which couple
      to the right-handed quark fields. The out-of-equilibrium decay of the Majorana
      fermion N mediated by the exchange of the scalar field X generates adequate
      baryon asymmetry for MN approximately 100 GeV and MX approximately TeV. The
      scalar partner of N (denoted N1) is naturally the lightest SUSY particle as it
      has no gauge interactions and plays the role of dark matter. The model is
      experimentally testable in (i) neutron-antineutron oscillations with a transition
      time estimated to be around 10(10)sec, (ii) discovery of colored particles X at
      LHC with mass of order TeV, and (iii) direct dark matter detection with a
      predicted cross section in the observable range.

PMID- 17501409
TI  - Complex hybrid inflation and baryogenesis.
AB  - We propose a hybrid inflation model with a complex waterfall field which contains
      an interaction term that breaks the U(1) global symmetry associated with the
      waterfall field charge. We show that the asymmetric evolution of the real and
      imaginary parts of the complex field during the phase transition at the end of
      inflation translates into a charge asymmetry. The latter strongly depends on the
      vacuum expectation value of the waterfall field, which is well constrained by
      diverse cosmological observations.

PMID- 17501410
TI  - Cancellations beyond finiteness in N=8 supergravity at three loops.
AB  - We construct the three-loop four-point amplitude of N=8 supergravity using the
      unitarity method. The amplitude is ultraviolet finite in four dimensions. Novel
      cancellations, not predicted by traditional superspace power-counting arguments,
      render its degree of divergence in D dimensions no worse than that of N=4 super
      Yang-Mills theory--a finite theory in four dimensions. Similar cancellations can
      be identified at all loop orders in certain unitarity cuts, suggesting that N=8
      supergravity may be a perturbatively finite theory of quantum gravity.

PMID- 17501411
TI  - Axino dark matter from Q-balls in Affleck-Dine baryogenesis and the Omega b-Omega
      DM coincidence problem.
AB  - We show that the Omega b-Omega DM coincidence can naturally be explained in a
      framework where axino is cold dark matter which is predominantly produced in
      nonthermal processes involving decays of Q-balls formed in Affleck-Dine
      baryogenesis. In this approach, the similarity of Omega b and Omega DM is a
      direct consequence of the (sub-)GeV scale of the mass of the axino, while the
      reheating temperature TR must be low, some 10(2) GeV, or less.

PMID- 17501414
TI  - Ramsey method of separated oscillatory fields for high-precision penning trap
      mass spectrometry.
AB  - Ramsey's method of separated oscillatory fields is applied to the excitation of
      the cyclotron motion of short-lived ions in a Penning trap to improve the
      precision of their measured mass values. The theoretical description of the
      extracted ion-cyclotron-resonance line shape is derived and its correctness
      demonstrated experimentally by measuring the mass of the short-lived 38Ca nuclide
      with an uncertainty of 1.1 x 10(-8) using the Penning trap mass spectrometer
      ISOLTRAP at CERN. The mass of the superallowed beta emitter 38Ca contributes for
      testing the theoretical corrections of the conserved-vector-current hypothesis of
      the electroweak interaction. It is shown that the Ramsey method applied to
      Penning trap mass measurements yields a statistical uncertainty similar to that
      obtained by the conventional technique but 10 times faster. Thus the technique is
      a new powerful tool for high-precision mass measurements.

PMID- 17501415
TI  - Four-body calculation of proton-3He scattering.
AB  - The four-body equations of Alt, Grassberger, and Sandhas are solved, for the
      first time, for proton-3He scattering including the Coulomb interaction between
      the three protons using the method of screening and renormalization as was done
      recently for proton-deuteron scattering. Various realistic two-nucleon potentials
      are used. Large Coulomb effects are seen on all observables. Comparison with data
      at different energies shows large deviations in the proton analyzing power but
      quite reasonable agreement in other observables. The effect of the nucleon
      nucleon magnetic moment interaction and correlations between p-d and p-3He
      analyzing powers are studied.

PMID- 17501416
TI  - Evidence for symplectic symmetry in Ab initio no-core shell model results for
      light nuclei.
AB  - Clear evidence for symplectic symmetry in low-lying states of 12C and 16O is
      reported. Eigenstates of 12C and 16O, determined within the framework of the no
      core shell model using the J-matrix inverse scattering potential with A<or=16
      (JISP16) nucleon-nucleon (NN) realistic interaction, typically project at the 85%
      90% level onto a few of the most deformed symplectic basis states that span only
      a small fraction of the full model space. The results are nearly independent of
      whether the bare or renormalized effective interactions are used in the analysis.
      The outcome confirms Elliott's SU(3) model which underpins the symplectic scheme,
      and above all, points to the relevance of a symplectic no-core shell model that
      can reproduce experimental B(E2) values without effective charges as well as
      deformed spatial modes associated with clustering phenomena in nuclei.

PMID- 17501417
TI  - Above threshold dissociation of vibrationally cold HD+ molecules.
AB  - The experimental study of molecular dissociation of H2+ by intense laser pulses
      is complicated by the fact that the ions are initially produced in a wide range
      of vibrational states, each of which responds differently to the laser field. An
      electrostatic storage device has been used to radiatively cool HD+ ions enabling
      the observation of above threshold dissociation from the ground vibrational state
      by 40 fs laser pulses at 800 nm. At the highest intensities used, dissociation
      through the absorption of at least four photons is found to be the dominant
      process.

PMID- 17501418
TI  - Enhanced transmission and reflection of few-cycle pulses by a single slit.
AB  - We show that a physical mechanism responsible for the enhanced transmission and
      reflection of ultrashort (few-cycle) pulses by a single subwavelength slit in a
      thick metallic film is the Fabry-Perot-like resonant excitation of stationary,
      quasistationary, and nonstationary waves inside the slit, which leads to the
      field enhancement inside and around the slit. The mechanism is universal for any
      pulse-scatter system, which supports the stationary resonances. We point out that
      there is a pulse duration limit below which the slit does not support the
      intraslit resonance.

PMID- 17501419
TI  - Displacement echoes: classical decay and quantum freeze.
AB  - Motivated by neutron scattering experiments, we investigate the decay of the
      fidelity with which a wave packet is reconstructed by a perfect time-reversal
      operation performed after a phase-space displacement. In the semiclassical limit,
      we show that the decay rate is generically given by the Lyapunov exponent of the
      classical dynamics. For small displacements, we additionally show that, following
      a short-time Lyapunov decay, the decay freezes well above the ergodic value
      because of quantum effects. Our analytical results are corroborated by numerical
      simulations.

PMID- 17501420
TI  - Observation of two-wave structure in strongly nonlinear dissipative granular
      chains.
AB  - In a strongly nonlinear viscous granular chain impacted by a single grain we
      observe a wave disturbance that consists of two parts exhibiting two time scales
      of dissipation. Above a critical viscosity there is no separation of the two
      pulses, and the dissipation and nonlinearity dominate the shocklike attenuating
      pulse.

PMID- 17501421
TI  - Taylor dispersion with absorbing boundaries: a stochastic approach.
AB  - We solve the problem of Taylor dispersion in the presence of absorbing boundaries
      using an exact stochastic formulation. In addition to providing a clear
      stochastic picture of Taylor dispersion, our method leads to closed-form
      expressions for all the moments of the convective displacement of the dispersing
      particles in terms of the transverse diffusion eigenmodes. We also find that the
      cumulants grow asymptotically linearly with time, ensuring a Gaussian
      distribution in the long-time limit. As a demonstration of the technique, the
      first two longitudinal cumulants (yielding respectively the effective velocity
      and the Taylor diffusion constant) as well as the skewness (a measure of the
      deviation from normality) are calculated for fluid flow in the parallel plate
      geometry. We find that the effective velocity and the skewness are enhanced while
      Taylor dispersion is suppressed due to absorption at the boundary.

PMID- 17501422
TI  - Gravity-free hydraulic jumps and metal femtoliter cups.
AB  - Hydraulic jumps created by gravity are seen everyday in the kitchen sink. We show
      that at small scales a circular hydraulic jump can be created in the absence of
      gravity by surface tension. The theory is motivated by our experimental finding
      of a height discontinuity in spreading submicron molten metal droplets created by
      pulsed-laser ablation. By careful control of initial conditions, this leads to
      solid femtoliter cups of gold, silver, copper, niobium, and tin.

PMID- 17501413
TI  - Scaling properties of azimuthal anisotropy in Au+Au and Cu+Cu Collisions at
      sqrt[s NN]=200 GeV.
AB  - Differential measurements of elliptic flow (v2) for Au+Au and Cu+Cu collisions at
      sqrt[sNN]=200 GeV are used to test and validate predictions from perfect fluid
      hydrodynamics for scaling of v2 with eccentricity, system size, and transverse
      kinetic energy (KE T). For KE T identical with mT-m up to approximately 1 GeV the
      scaling is compatible with hydrodynamic expansion of a thermalized fluid. For
      large values of KE T mesons and baryons scale separately. Quark number scaling
      reveals a universal scaling of v2 for both mesons and baryons over the full KE T
      range for Au+Au. For Au+Au and Cu+Cu the scaling is more pronounced in terms of
      KE T, rather than transverse momentum.

PMID- 17501424
TI  - Feasibility of an electron-based crystalline undulator.
AB  - The feasibility to generate powerful monochromatic radiation of the undulator
      type in the gamma region of the spectrum by means of planar channeling of
      ultrarelativistic electrons in a periodically bent crystal is proven. It is shown
      that to overcome the restriction due to the smallness of the dechanneling length,
      an electron-based crystalline undulator must operate in the regime of higher beam
      energies than a positron-based one does. A numerical analysis is performed for a
      50 GeV electron channeling in Si along the (111) crystallographic planes.

PMID- 17501423
TI  - Turbulent diamagnetism in flowing liquid sodium.
AB  - The nature of Ohm's law is examined in a turbulent flow of liquid sodium. A
      magnetic field is applied to the flowing sodium, and the resulting magnetic field
      is measured. The mean velocity field of the sodium is also measured in an
      identical-scale water model of the experiment. These two fields are used to
      determine the terms in Ohm's law, indicating the presence of currents driven by a
      turbulent electromotive force. These currents result in a diamagnetic effect,
      generating magnetic field in opposition to the dominant fields of the experiment.
      The magnitude of the fluctuation-driven magnetic field is comparable to that of
      the field induced by the sodium's mean flow.

PMID- 17501425
TI  - Ultrashort-pulse child-langmuir law in the quantum and relativistic regimes.
AB  - This Letter presents a consistent quantum and relativistic model of short-pulse
      Child-Langmuir (CL) law, of which the pulse length tau is less than the electron
      transit time in a gap of spacing D and voltage V. The classical value of the
      short-pulse CL law is enhanced by a large factor due to quantum effects when the
      pulse length and the size of the beam are, respectively, in femtosecond duration
      and nanometer scale. At high voltage larger than the electron rest mass,
      relativistic effects will suppress the enhancement of short-pulse CL law, which
      is confirmed by particle-in-cell simulation. When the pulse length is much
      shorter than the gap transit time, the current density is proportional to V, and
      to the inverse power of D and tau.

PMID- 17501426
TI  - Experimental evidence of a zonal magnetic field in a toroidal plasma.
AB  - A zonal magnetic field is found in a toroidal plasma. The magnetic field has a
      symmetric bandlike structure, which is uniform in the toroidal and poloidal
      directions and varies radially with a finite wavelength of mesoscale, which is
      analogous to zonal flows. A time-dependent bicoherence analysis reveals that the
      magnetic field should be generated by the background plasma turbulence. The
      discovery is classified as a new kind of phenomenon of structured magnetic field
      generation, giving insight into phenomena such as dipole field generation in
      rotational planets.

PMID- 17501427
TI  - Ostwald ripening, chiral crystallization, and the common-ancestor effect.
AB  - We introduce an agent-based model for advection-mediated chiral autocatalysis in
      which we take into account dissolution-crystallization processes through Ostwald
      ripening. We demonstrate that the latter phenomenon is the key to explaining
      previously puzzling experimental results whereby complete chiral symmetry
      breaking is attained from an initially unbiased mixture of seed crystals. We show
      that this homochirality is achieved by what has been termed the common-ancestor
      effect: Ostwald ripening removes competing lineages, leaving only one common
      ancestor for the entire system.

PMID- 17501428
TI  - Linear grain growth kinetics and rotation in nanocrystalline Ni.
AB  - We report three-dimensional atomistic molecular dynamics studies of grain growth
      kinetics in nanocrystalline Ni. The results show the grain size increasing
      linearly with time, contrary to the square root of the time kinetics observed in
      coarse-grained structures. The average grain boundary energy per unit area
      decreases simultaneously with the decrease in total grain boundary area
      associated with grain growth. The average mobility of the boundaries increases as
      the grain size increases. The results can be explained by a model that considers
      a size effect in the boundary mobility.

PMID- 17501412
TI  - Observation of WZ production.
AB  - We report the first observation of the associated production of a W boson and a Z
      boson. This result is based on 1.1 fb;-1 of integrated luminosity from pp
      collisions at sqrt[s]=1.96 TeV collected with the CDF II detector at the Fermilab
      Tevatron. We observe 16 WZ candidates passing our event selection with an
      expected background of 2.7+/-0.4 events. A fit to the missing transverse energy
      distribution indicates an excess of events compared to the background expectation
      corresponding to a significance equivalent to 6 standard deviations. The measured
      cross section is sigma(pp-->WZ)=5.0(-1.6)(+1.8) pb, consistent with the standard
      model expectation.

PMID- 17501429
TI  - Pressure-driven "molecular metal" to "atomic metal" transition in crystalline Ga.
AB  - We present the ultrasonic study of gallium (Ga I) under high pressure up to 1.7
      GPa, including the measurements of the density and elastic properties during
      phase transitions to Ga II and to a liquid state. The observed large drop of both
      bulk and shear moduli (by 30% and 55%, correspondingly) during the phase
      transition to Ga II, as well as the increase of the Poisson's ratio from
      typically "covalent" ( approximately 0.22) to "metallic" ( approximately 0.32)
      values, experimentally testifies to the coexistence of a molecular and metallic
      behavior in Ga I and to the disappearance of the "covalency" during the
      transition to Ga II. A high value of the pressure derivative of the bulk modulus
      for Ga I and the increase in the Poisson's ratio can be associated with the
      weakening of the covalency in compressed Ga I and considered as a precursor of
      the transition to normal metal.

PMID- 17501430
TI  - Experimental evidence for a new parameter to control the glass transition of
      confined polymers.
AB  - Polymer nanocomposites can be used to study confinement effects on the polymer
      glass transition temperature (Tg) in a controlled manner by varying interparticle
      spacing. Using gold nanoparticles in polymethylmethacrylate, we show how the
      polymer Tg can be tuned by variation of the nanoparticle-polymer interface width
      (sigma), keeping interparticle spacing fixed. We report the first experimental
      observation of a crossover in the sign of Tg deviation for confined polymers by
      variation of sigma and propose a model to explain the dependence of crossover
      width on the spatial extent of cooperatively rearranging regions.

PMID- 17501431
TI  - Alloying mechanisms for epitaxial nanocrystals.
AB  - The different mechanisms involved in the alloying of epitaxial nanocrystals are
      reported in this Letter. Intermixing during growth, surface diffusion, and
      intraisland diffusion were investigated by varying the growth conditions and
      annealing environments during chemical vapor deposition. The relative importance
      of each mechanism was evaluated in determining a particular composition profile
      for dome-shaped Ge:Si (001) islands. For samples grown at a faster rate,
      intermixing during growth was reduced. Si surface diffusion dominates during H2
      annealing, whereas Ge surface diffusion and intraisland diffusion prevail during
      annealing in a PH3 environment.

PMID- 17501432
TI  - Polarization effects on the surface chemistry of PbTiO3-supported Pt films.
AB  - To demonstrate a new paradigm of dynamical control of surface structure and
      reactivity, we perform density functional theory calculations of the adsorption
      of several molecules and atoms to the surface of ultrathin Pt(100) films
      supported on ferroelectric PbTiO3. We show that reorienting the polarization
      direction of the substrate can dramatically change the chemisorption energies of
      CO, O, C, and N and alter the reaction pathways for dissociation of CO, O2, N2,
      and NO. We discuss the structural and electronic effects of a polarized substrate
      on the metal surface, and we suggest potential applications in tunable catalysis.

PMID- 17501433
TI  - New self-limiting assembly model for Si quantum rings on Si(100).
AB  - We propose a new self-limiting assembly model for Si quantum rings on Si(100)
      where the ring's formation and evolution are driven by a growth-etching
      competition mechanism. The as-grown ring structure in a plasma enhanced chemical
      vapor deposition system has excellent rotational symmetry and superior morphology
      with a typical diameter, edge width, and height of 150-300, 10, and 5 nm,
      respectively. Based on this model, the size and morphology can be controlled well
      by simply tuning the timing procedure. We suggest that this growth model is not
      limited to certain material system, but provides a general scheme to control and
      tailor the self-assembly nanostructures into the desired size, shape, and
      complexity.

PMID- 17501434
TI  - Spatial variations in submolecular vibronic spectroscopy on a thin insulating
      film.
AB  - Scanning tunneling spectroscopy on single naphthalocyanine molecules adsorbed on
      an ultrathin aluminum oxide film exhibits electron-vibronic coupling that varies
      with the position of tunneling over the molecule. The spectra at different
      positions are composed of several series of equally spaced peaks, which are
      interpreted as progression of progressions of molecular vibrational modes. The
      spatial variations correlate with the molecular orbital structure, revealing
      spatially dependent electron-vibronic coupling and selective vibrational
      excitation.

PMID- 17501435
TI  - Identification of Ge/Si intermixing processes at the Bi/Ge/Si(111) surface.
AB  - The chemical contrast between Si and Ge obtained by scanning tunneling microscopy
      on Bi-covered Si(111) surfaces is used as a tool to identify two vertical Ge/Si
      intermixing processes. During annealing of an initially pure Ge monolayer on Si,
      the intermixing is confined to the first two layers approaching a 50% Ge
      concentration in each layer. During epitaxial growth, a growth front induced
      intermixing process acting at step edges is observed. Because of the open atomic
      structure at the step edges, relative to the terraces, a lower activation barrier
      for intermixing at the step edge, compared to the terrace, is observed.

PMID- 17501436
TI  - Dynamics and hysteresis of the contact line between liquid hydrogen and cesium
      substrates.
AB  - We have measured both the hysteresis and the dynamics of the edge of a liquid
      hydrogen meniscus on several solid cesium substrates. We find that the dynamics
      of the contact line is thermally activated. For all substrates, we find that the
      activation energy is of the order of the hysteresis. We show that the pinning of
      the contact line on mesoscopic defects of the Cs substrate is likely to control
      both the hysteresis and the dynamics of the contact line at low velocity, close
      to the depinning threshold. Such a mechanism could be relevant also for simple
      room-temperature systems.

PMID- 17501437
TI  - Length-dependent conductance of a spin-incoherent Hubbard chain: Monte Carlo
      calculations.
AB  - The dc conductance of a short spin-incoherent Hubbard chain coupled to leads is
      investigated using quantum Monte Carlo calculations. In contrast with the
      Luttinger liquid regime, where the conductance is equal to the noninteracting
      value, the spin-incoherent regime displays a conductance that decreases rapidly
      with chain length down to a value of roughly 1.5 e2/h for a four site chain
      followed by a slower decrease for longer chains. We also discuss the resistance
      contribution from scattering in the contacts.

PMID- 17501438
TI  - Doped Mott insulator as the origin of heavy-fermion behavior in LiV2O4.
AB  - We investigate the electronic structure of LiV2O4, for which heavy-fermion
      behavior has been observed in various experiments, by the combination of the
      local density approximation and dynamical mean field theory. To obtain results at
      zero temperature, we employ the projective quantum Monte Carlo method as an
      impurity solver. Our results show that the strongly correlated a 1g band is a
      lightly doped Mott insulator which, at low temperatures, shows a sharp (heavy)
      quasiparticle peak just above the Fermi level, which is consistent with recent
      photoemission experiments by Shimoyamada et al. [Phys. Rev. Lett. 96, 026403
      (2006)10.1103/PhysRevLett.96.026403].

PMID- 17501439
TI  - Revealing charge density wave formation in the LaTe2 system by angle resolved
      photoemission spectroscopy.
AB  - We present the first direct study of charge density wave (CDW) formation in quasi
      2D single layer LaTe2 using high-resolution angle resolved photoemission
      spectroscopy and low energy electron diffraction. CDW formation is driven by
      Fermi surface (FS) nesting, however, characterized by a surprisingly smaller gap
      ( approximately 50 meV) than seen in the double layer RTe2 compounds, extending
      over the entire FS. This establishes LaTe2 as the first reported semiconducting
      2D CDW system where the CDW phase is FS nesting driven. In addition, the layer
      dependence of this phase in the tellurides and the possible transition from a
      stripe to a checkerboard phase is discussed.

PMID- 17501440
TI  - Field-induced Fermi surface reconstruction and adiabatic continuity between
      antiferromagnetism and the hidden-order state in URu2Si2.
AB  - Shubnikov-de Haas oscillations reveal at high fields an abrupt reconstruction of
      the Fermi surface within the hidden-order (HO) phase of URu2Si2. Taken together
      with reported Hall effect results, this implies an increase in the effective
      carrier density and suggests that the field suppression of the HO state is
      ultimately related to destabilizing a gap in the spectrum of itinerant
      quasiparticles. While hydrostatic pressure favors antiferromagnetism in detriment
      to the HO state, it has a modest effect on the complex H-T phase diagram. Instead
      of phase separation between HO and antiferromagnetism our observations indicate
      adiabatic continuity between both orderings with field and pressure changing
      their relative weight.

PMID- 17501441
TI  - Excitonic condensation under spin-orbit coupling and BEC-BCS crossover.
AB  - The condensation of electron-hole pairs is studied at zero temperature and in the
      presence of a weak spin-orbit coupling (SOC) in coupled quantum wells. Under
      realistic conditions, a perturbative SOC can have observable effects in the order
      parameter of the condensate. First, the fermion exchange symmetry is absent. As a
      result, the condensate spin has no definite parity. Additionally, the excitonic
      SOC breaks the rotational symmetry yielding a complex order parameter in an
      unconventional way; i.e., the phase pattern of the order parameter is a function
      of the condensate density. This is manifested through finite off-diagonal
      components of the static spin susceptibility, suggesting a new experimental
      method to confirm an excitonic condensate.

PMID- 17501442
TI  - Mesoscopic magnetic states in metallic alloys with strong electronic
      correlations: a percolative scenario for CeNi 1-x Cux.
AB  - We present evidence for the existence of magnetic clusters of approximately 20 A
      in the strongly correlated alloy system CeNi 1-x Cux (0.7<or=x<or=0.2) based on
      small angle neutron scattering experiments as well as the occurrence of
      staircaselike hysteresis cycles at very low temperature (100 mK). An unusual
      feature is the observation of long-range ferromagnetic order below the cluster
      glass transition without any indication of a sharp transition at a Curie
      temperature. These observations strongly support a phenomenological model where a
      percolative process connects both magnetic states. The model can account for all
      the puzzling data previously obtained in this system, providing a new perspective
      with regard to the magnetic ground state of other alloyed compounds with small
      magnetic moments or weak ferromagnetism with intrinsic disorder effects.

PMID- 17501443
TI  - Impact of space-energy correlation on variable range hopping in a transistor.
AB  - Hopping conduction in transistors, i.e., under a transverse electric field, is
      addressed using percolation theory with a space-energy correlation in the density
      of states of the impurity band. The computation of the percolation threshold over
      an extended range of correlation parameters enables us to derive a formula,
      which, while giving the classical results in the low field limit, describes the
      emergence of a specific variable range hopping in the high field case. An
      application of this formula to experimentally extract the localization radius is
      also proposed.

PMID- 17501444
TI  - Oscillating Nernst-Ettingshausen effect in bismuth across the quantum limit.
AB  - In elemental bismuth, 10(5) atoms share a single itinerant electron. Therefore, a
      moderate magnetic field can confine electrons to the lowest Landau level. We
      report on the first study of metallic thermoelectricity in this regime. The main
      thermoelectric response is off-diagonal with an oscillating component several
      times larger than the nonoscillating background. When the first Landau level
      attains the Fermi energy, both the Nernst and the Ettingshausen coefficients
      sharply peak, and the latter attains a temperature-independent maximum. These
      features are yet to be understood. We note a qualitative agreement with a theory
      invoking current-carrying edge excitations.

PMID- 17501445
TI  - Magnetothermoelectric response at a superfluid-Mott-insulator transition.
AB  - We investigate the finite temperature magnetothermoelectric response in the
      vicinity of a superfluid-Mott-insulator quantum phase transition. We focus on the
      particle-hole symmetric transitions of the Bose-Hubbard model, and combine
      Lorentz invariance arguments with quantum Boltzmann calculations. By means of an
      epsilon expansion, we find that a nonvanishing thermoelectric tensor and a finite
      thermal transport coefficient are supported in this quantum critical regime. We
      comment on the singular Nernst effect in this problem.

PMID- 17501446
TI  - Electric field effect tuning of electron-phonon coupling in graphene.
AB  - Gate-modulated low-temperature Raman spectra reveal that the electric field
      effect (EFE), pervasive in contemporary electronics, has marked impacts on long
      wavelength optical phonons of graphene. The EFE in this two-dimensional honeycomb
      lattice of carbon atoms creates large density modulations of carriers with linear
      dispersion (known as Dirac fermions). Our EFE Raman spectra display the
      interactions of lattice vibrations with these unusual carriers. The changes of
      phonon frequency and linewidth demonstrate optically the particle-hole symmetry
      about the charge-neutral Dirac point. The linear dependence of the phonon
      frequency on the EFE-modulated Fermi energy is explained as the electron-phonon
      coupling of massless Dirac fermions.

PMID- 17501447
TI  - Terahertz current oscillations in single-walled zigzag carbon nanotubes.
AB  - We report time-dependent terahertz current oscillations on an n=10 single-walled
      zigzag carbon nanotube (CNT) that is 100 nm long. To obtain transport
      characteristics in this CNT, we developed an ensemble Monte Carlo (MC) simulator,
      which self-consistently calculates the electron transport and electrical
      potential. The ensemble MC simulations indicate that, under certain dc bias and
      doping conditions, the average electron velocity and concentration oscillate.
      This leads to current oscillations in space and time, on the tube, and at the
      contacts. We attribute this to accumulation and depletion of the CNT electrons at
      different locations on the tube, giving rise to low and high density electron
      regions. These local dipoles are a result of intra- and intersubband scatterings
      and different subband dispersion relations. This in turn forms propagating
      dipoles and current oscillations.

PMID- 17501448
TI  - B80 fullerene: an Ab initio prediction of geometry, stability, and electronic
      structure.
AB  - The geometry, electronic, and structural properties of an unusually stable boron
      cage made of 80 boron atoms are studied, using ab initio calculations. The shape
      of this cluster is very similar to that of the well-known C60 fullerene, but in
      the B80 case, there is an additional atom in the center of each hexagon. The
      resulting cage preserves the Ih symmetry, has a relatively large highest occupied
      and lowest unoccupied energy gap ( approximately 1 eV) and, most importantly, is
      energetically more stable than boron double rings, which were detected in
      experiments and considered as building blocks of boron nanotubes. To our
      knowledge, this is the most stable boron cage studied so far.

PMID- 17501449
TI  - Elucidation of the electronic structure of semiconducting single-walled carbon
      nanotubes by electroabsorption spectroscopy.
AB  - We report benchmark calculations of electroabsorption in semiconducting single
      walled carbon nanotubes that provide motivation to perform electroabsorption
      measurement on these systems. We show that electroabsorption can detect the
      continuum bands in different energy manifolds. Direct determination of the
      binding energies of excitons in higher manifolds thereby becomes possible. We
      also find that electroabsorption can provide evidence for Fano-type coupling
      between the second exciton and the lowest continuum band states.

PMID- 17501450
TI  - Relaxation time of a chiral quantum R-L circuit.
AB  - We report on the GHz complex admittance of a chiral one-dimensional ballistic
      conductor formed by edge states in the quantum Hall regime. The circuit consists
      of a wide Hall bar (the inductor L) in series with a tunable resistor (R) formed
      by a quantum point contact. Electron interactions between edges are screened by a
      pair of side gates. Conductance steps are observed on both real and imaginary
      parts of the admittance. Remarkably, the phase of the admittance is transmission
      independent. This shows that the relaxation time of a chiral R -L circuit is
      resistance independent. A current and charge conserving scattering theory is
      presented that accounts for this observation with a relaxation time given by the
      electronic transit time in the circuit.

PMID- 17501451
TI  - Magnetic-field effects on the size of vortices below the surface of NbSe2
      detected using low energy beta-NMR.
AB  - A low energy radioactive beam of polarized 8Li has been used to observe the
      vortex lattice near the surface of superconducting NbSe2. The inhomogeneous
      magnetic-field distribution associated with the vortex lattice was measured using
      depth-resolved beta-detected NMR. Below Tc, one observes the characteristic line
      shape for a triangular vortex lattice which depends on the magnetic penetration
      depth and vortex core radius. The size of the vortex core varies strongly with
      the magnetic field. In particular, in a low field of 10.8 mT, the core radius is
      much larger than the coherence length. The possible origin of these giant
      vortices is discussed.

PMID- 17501452
TI  - Topological change of the Fermi surface in low-density Rashba gases: application
      to superconductivity.
AB  - In this Letter we show how, for small values of the Fermi energy compared to the
      spin-orbit splitting of Rashba type, a topological change of the Fermi surface
      leads to an effective reduction of the dimensionality in the electronic density
      of states in the low charge density regime. We investigate its consequences on
      the onset of the superconducting instability. We show that the superconducting
      critical temperature is significantly tuned in this regime by the spin-orbit
      coupling. We suggest that materials with strong spin-orbit coupling are good
      candidates for enhanced superconductivity.

PMID- 17501453
TI  - High-energy kink observed in the electron dispersion of high-temperature cuprate
      superconductors.
AB  - Photoemission studies show the presence of a high-energy anomaly in the observed
      band dispersion for two families of cuprate superconductors, Bi2Sr2CaCu2O8+delta
      and La 2-x BaxCuO4. The anomaly, which occurs at a binding energy of
      approximately 340 meV, is found to be anisotropic and relatively weakly doping
      dependent. Scattering from short range or nearest neighbor spin excitations is
      found to supply an adequate description of the observed phenomena.

PMID- 17501454
TI  - Interplay of anisotropy and disorder in the doping-dependent melting and glass
      transitions of vortices in Bi2Sr2CaCu2O 8+delta.
AB  - We study the oxygen doping dependence of the equilibrium first-order melting and
      second-order glass transitions of vortices in Bi2Sr2CaCu2O 8+delta. Doping
      affects both anisotropy and disorder. Anisotropy scaling is shown to collapse the
      melting lines only where thermal fluctuations are dominant. Yet, in the region
      where disorder breaks that scaling, the glass lines are still collapsed. A
      quantitative fit to melting and replica symmetry-breaking lines of a 2D Ginzburg
      Landau model further reveals that disorder amplitude weakens with doping, but to
      a lesser degree than thermal fluctuations, enhancing the relative role of
      disorder.

PMID- 17501455
TI  - Reentrant orbital order and the true ground state of LaSr2Mn2O7.
AB  - Contrary to conventional wisdom, our purified La 2-2x Sr 1+2x Mn2O7 crystals
      exhibit CE-type orbital and charge order as the low-temperature ground state for
      a hole doping level h=0.5. For small deviations from h=0.5, the high-temperature
      CE phase is replaced at low temperatures by an A-type antiferromagnet without
      coexistence. Larger deviations result in a lack of CE order at any temperature.
      Thus, small inhomogeneities in cation or oxygen composition could explain why
      others commonly see this reentrance with coexistence.

PMID- 17501456
TI  - Excitations from a Bose-Einstein condensate of magnons in coupled spin ladders.
AB  - The weakly coupled quasi-one-dimensional spin ladder compound (CH3)2CHNH3CuCl3 is
      studied by neutron scattering in magnetic fields exceeding the critical field of
      Bose-Einstein condensation of magnons. Commensurate long-range order and the
      associated Goldstone mode are detected and found to be similar to those in
      reference to spin-dimer materials. However, for the upper two massive magnon
      branches, the observed behavior is totally different, culminating in a drastic
      collapse of excitation bandwidth beyond the transition point.

PMID- 17501457
TI  - Chaotic quivering of micron-scaled on-chip resonators excited by centrifugal
      optical pressure.
AB  - Opto-mechanical chaotic oscillation of an on-chip resonator is excited by the
      radiation-pressure nonlinearity. Continuous optical input, with no external
      feedback or modulation, excites chaotic vibrations in very different geometries
      of the cavity (both tori and spheres) and shows that opto-mechanical chaotic
      oscillations are an intrinsic property of optical microcavities. Measured
      phenomena include period doubling, a spectral continuum, aperiodic oscillations,
      and complex trajectories. The rate of exponential divergence from a perturbed
      initial condition (Lyapunov exponent) is calculated. Continuous improvements in
      cavities mean that such chaotic oscillations can be expected in the future with
      many other platforms, geometries, and frequency spans.

PMID- 17501458
TI  - Quantum oscillations of the total spin in a heterometallic antiferromagnetic
      ring: evidence from neutron spectroscopy.
AB  - Using inelastic neutron scattering and applied fields up to 11.4 T, we have
      studied the spin dynamics of the Cr7Ni antiferromagnetic ring in the energy
      window 0.05-1.6 meV. We demonstrate that the external magnetic field induces an
      avoided crossing (anticrossing) between energy levels with different total-spin
      quantum numbers. This corresponds to quantum oscillations of the total spin of
      each molecule. The inelastic character of the observed excitation and the field
      dependence of its linewidth indicate that molecular spins oscillate coherently
      for a significant number of cycles. Precise signatures of the anticrossing are
      also found at higher energy, where measured and calculated spectra match very
      well.

PMID- 17501459
TI  - Time-resolved torsional relaxation of spider draglines by an optical technique.
AB  - The sensitivity of the torsional pendulum demonstrates the self-shape-memory
      effect in different types of spider draglines. Here we report the time-resolved
      noncovalent bonds recovery in the protein structure. The torsional dynamics of
      such multilevel structure governed by reversible interactions are described in
      the frame of a nested model. Measurement of three different relaxation times
      confirms the existence of three energy storage levels in such two protein
      spidroin systems. Torsion opens the way to further investigations towards
      unraveling the tiny torque effects in biological molecules.

PMID- 17501460
TI  - Multipole interference in the second-harmonic optical radiation from gold
      nanoparticles.
AB  - We provide experimental evidence of higher multipole (magnetic dipole and
      electric quadrupole) radiation in second-harmonic (SH) generation from arrays of
      metal nanoparticles. Fundamental differences in the radiative properties of
      electric dipoles and higher multipoles yield opposite interference effects
      observed in the SH intensities measured in the reflected and transmitted
      directions. These interference effects clearly depend on the polarization of the
      fundamental field, directly indicating the importance of multipole effects in the
      nonlinear response. We estimate that higher multipoles contribute up to 20% of
      the total emitted SH field amplitude for certain polarization configurations.

PMID- 17501461
TI  - Carrier-envelope-offset phase control of ultrafast optical rectification in
      resonantly excited semiconductors.
AB  - Ultrashort pulse light-matter interactions in a semiconductor are investigated
      within the regime of resonant optical rectification. Using pulse envelope areas
      of around 1.5-3.5 pi, a single-shot dependence on carrier-envelope-offset phase
      (CEP) is demonstrated for 5 fs pulse durations. A characteristic phase map is
      predicted for several different frequency regimes using parameters for thin-film
      GaAs. We subsequently suggest a possible technique to extract the CEP, in both
      sign and amplitude, using a solid state detector.

PMID- 17501462
TI  - Photon emission as a source of coherent behavior of polaritons.
AB  - We show that the combined effect of photon emission and Coulomb interactions may
      drive an exciton-polariton system towards a dynamical coherent state, even
      without phonon thermalization or any other relaxation mechanism. Exact
      diagonalization results for a finite system (a multilevel quantum dot interacting
      with the lowest-energy photon mode of a microcavity) are presented in support of
      this statement.

PMID- 17501463
TI  - Polarized photoluminescence excitation spectroscopy of single-walled carbon
      nanotubes.
AB  - The polarized photoluminescence excitation spectra of twenty-five single-walled
      carbon nanotube species are reported. For light polarized along the nanotube
      axis, the main absorption resonance at E22 shows sidebands attributed to phonon
      assisted absorption. Sidebands to E11 have a diameter dependent energy and are
      assigned to excited excitonic states. Along with longitudinal excitations,
      several transverse excitations are identified. The transverse E12 resonance has a
      specific family pattern with energy close to E22. Comparison with theory provides
      an estimate of the strength of the Coulomb interaction.

PMID- 17501464
TI  - Rheological observation of glassy dynamics of dilute polymer solutions near the
      coil-stretch transition in elongational flows.
AB  - It has long been conjectured that the macroscopic dynamics of dilute polymer
      solutions may exhibit a glasslike slowdown caused by ergodicity breaking, in the
      vicinity of the coil-stretch transition in elongational flows. We report
      experimental observations using a filament stretching rheometer that confirm the
      existence of such glassy states. It is observed that different time-dependent
      elongational strain-rate profiles lead to a pronounced history dependence and
      aging effects within a narrow range of strain rates. The results have a direct
      bearing on the analysis and design of processes employing dilute polymer
      solutions, such as ink-jet printing, surface coating, and turbulent-drag
      reduction.

PMID- 17501465
TI  - Molecular theory of physical aging in polymer glasses.
AB  - A molecular level theory for the physical aging of polymer glasses is proposed.
      The nonequilibrium time evolution of the amplitude of long wavelength density
      fluctuations, and its influence on activated barrier hopping, plays an essential
      role. The theory predicts temperature-dependent apparent power-law aging of the
      segmental relaxation time and logarithmic aging of thermodynamiclike properties,
      in good accord with experiments. A physical origin for the quantitative
      nonuniversal aspects based on the amplitude of quenched density fluctuations is
      suggested.

PMID- 17501466
TI  - Physical basis for membrane-charge selectivity of cationic antimicrobial
      peptides.
AB  - Antimicrobial peptides are known to selectively disrupt (highly charged)
      microbial membranes by asymmetrical incorporation into the outer layers. We
      present a physical basis for membrane-charge selectivity of cationic
      antimicrobial peptides. In particular, we provide a clear picture of how peptide
      charge Q influences the asymmetrical insertion--one salient feature is the
      existence of an optimal peptide charge, at which selective insertion is
      optimized. Our results suggest that large Q is required for antimicrobial
      selectivity, consistent with experiments.

PMID- 17501467
TI  - Combined effect of pore radius and protein dielectric coefficient on the
      selectivity of a calcium channel.
AB  - Calcium-selective ion channels often contain a selectivity filter made of similar
      amino acids, rich in carboxlylates, although the Ca2+ affinities of these
      channels range from micromolar to millimolar. To understand the physical
      mechanism for this range of affinities, we use grand canonical Monte Carlo
      simulations to study the competition of Na+ and Ca2+ in the selectivity filter of
      a reduced model of a Ca channel. We show that Ca2+ affinity is increased
      dramatically when both the volume and dielectric coefficient of the protein are
      reduced.

PMID- 17501468
TI  - Membrane waves driven by actin and Myosin.
AB  - We present a model which couples the membrane with the protrusive forces of actin
      polymerization and contractile forces of molecular motors, such as myosin. The
      actin polymerization at the membrane is activated by freely diffusing membrane
      proteins that have a spontaneous curvature. Molecular motors are recruited to the
      polymerizing actin filaments, from a constant reservoir, and produce a
      contractile force. All the forces and variables are treated in the linear limit.
      Our results show that for convex membrane proteins the myosin activity gives rise
      to robust transverse membrane waves, similar to those observed on different
      cells.

PMID- 17501469
TI  - Polymer chain dynamics in a random environment: heterogeneous mobilities.
AB  - We present a neutron scattering investigation on a miscible blend of two polymers
      with greatly different glass-transition temperatures Tg. Under such conditions,
      the nearly frozen high-Tg component imposes a random environment on the mobile
      chain. The results demand the consideration of a distribution of heterogeneous
      mobilities in the material and demonstrate that the larger scale dynamics of the
      fast component is not determined by the average local environment alone. This
      distribution of mobilities can be mapped quantitatively on the spectrum of local
      relaxation rates measured at high momentum transfers.

PMID- 17501470
TI  - Manipulating single enzymes by an external harmonic force.
AB  - We study a Michaelis-Menten reaction for a single two-state enzyme molecule,
      whose transition rates between the two conformations are modulated by an
      harmonically oscillating external force. In particular, we obtain a range of
      optimal driving frequencies for changing the conformation of the enzyme, thereby
      controlling the enzymatic activity (i.e., product formation). This analysis
      demonstrates that it is, in principle, possible to obtain information about
      particular rates within the kinetic scheme.

PMID- 17501471
TI  - Self-sustained spatiotemporal oscillations induced by membrane-bulk coupling.
AB  - We propose a novel mechanism leading to spatiotemporal oscillations in extended
      systems that does not rely on local bulk instabilities. Instead, oscillations
      arise from the interaction of two subsystems of different spatial dimensionality.
      Specifically, we show that coupling a passive diffusive bulk of dimension d with
      an excitable membrane of dimension d-1 produces a self-sustained oscillatory
      behavior. An analytical explanation of the phenomenon is provided for d=1.
      Moreover, in-phase and antiphase synchronization of oscillations are found
      numerically in one and two dimensions. This novel dynamic instability could be
      used by biological systems such as cells, where the dynamics on the cellular
      membrane is necessarily different from that of the cytoplasmic bulk.

PMID- 17501491
TI  - Methane dissociation on Ni(111): the role of lattice reconstruction.
AB  - The effects of lattice motion and reconstruction on the dissociation of methane
      on Ni(111) are explored, using both electronic structure theory and quantum
      dynamical calculations. We show that during the reaction, the Ni lattice
      reconstructs, effectively lowering the barrier to reaction, in contrast with
      earlier models of this process.

PMID- 17501508
TI  - Towards an exact treatment of exchange and correlation in materials: application
      to the "CO adsorption puzzle" and other systems.
AB  - It is shown that the errors of present-day exchange-correlation (XC) functionals
      are rather short ranged. For extended systems, the correction can therefore be
      evaluated by analyzing properly chosen clusters and employing highest-quality
      quantum chemistry methods. The XC correction rapidly approaches a universal
      dependence with cluster size. The method is applicable to bulk systems as well as
      to defects in the bulk and at surfaces. It is demonstrated here for CO adsorption
      at transition-metal surfaces, where present-day XC functionals dramatically fail
      to predict the correct adsorption site, and for the crystal bulk cohesive energy.

PMID- 17501510
TI  - Electrophoresis of colloidal dispersions in the low-salt regime.
AB  - We study the electrophoretic mobility of spherical charged colloids in a low-salt
      suspension as a function of the colloidal concentration. Using an effective
      particle charge and a reduced screening parameter, we map the data for systems
      with different particle charges and sizes, including numerical simulation data
      with full electrostatics and hydrodynamics and experimental data for latex
      dispersions, on a single master curve. We observe two different volume fraction
      dependent regimes for the electrophoretic mobility that can be explained in terms
      of the static properties of the ionic double layer.

PMID- 17501514
TI  - Exciton dissociation in organic light emitting diodes at the donor-acceptor
      interface.
AB  - Experimental in situ photoluminescence and transient photovoltage results show
      that the interface formed by N, N{'}-Bis(naphthalene-1-yl)-N, N{'}-bis(phenyl)
      benzidine (NPB) and tris(8-hydroxyquinoline) aluminum (Alq{3}) acts as an exciton
      dissociation site. Because of this dissociation effect, excitons formed in NPB at
      or within a diffusion length of the interface tend to dissociate before they
      radiatively decay to generate blue light. This suggests that the action of the
      "hole-blocking layer" used in indium tin oxide?NPB?hole-blocking
      layer?Alq{3}?aluminium to promote blue light emission from the NPB is more
      "exciton dissociation inhibition" than "hole blocking."

PMID- 17501520
TI  - Aharonov-Bohm conductance modulation in ballistic carbon nanotubes.
AB  - We report on magnetoconductance experiments in ballistic multiwalled carbon
      nanotubes threaded by magnetic fields as large as 55 T. In the high temperature
      regime (100 K), giant modulations of the conductance, mediated by the Fermi level
      location, are unveiled. The experimental data are consistently analyzed in terms
      of the field-dependent density of states of the external shell that modulates the
      injection properties at the electrode-nanotube interface, and the resulting
      linear conductance. This is the first unambiguous experimental evidence of
      Aharonov-Bohm effect in clean multiwalled carbon nanotubes.

PMID- 17501523
TI  - Weak localization in bilayer graphene.
AB  - We have performed the first experimental investigation of quantum interference
      corrections to the conductivity of a bilayer graphene structure. A negative
      magnetoresistance--a signature of weak localization--is observed at different
      carrier densities, including the electroneutrality region. It is very different,
      however, from the weak localization in conventional two-dimensional systems. We
      show that it is controlled not only by the dephasing time, but also by different
      elastic processes that break the effective time-reversal symmetry and provide
      intervalley scattering.

PMID- 17501525
TI  - Statistical approach to investigating transport through single molecules.
AB  - We present a statistical approach that combines comprehensive current-voltage
      data acquisition during the controlled manipulation of a molecular junction with
      subsequent statistical analysis. Thereby the most probable transport
      characteristics can be determined. The excellent sensitivity of this impartial
      approach to even subnanometer-long molecules is illustrated by benzene-1,4
      dithiol and 4,4"-bis(acetylthiol)-2,2',5',2"-tetramethyl-[1,1';4',1"] terphenyl
      results.

PMID- 17501535
TI  - Ion-specific anomalous electrokinetic effects in hydrophobic nanochannels.
AB  - We show with computer simulations that anomalous electrokinetic effects, such as
      ion specificity and nonzero zeta potentials for uncharged surfaces, are generic
      features of electro-osmotic flow in hydrophobic channels. This behavior is due to
      the stronger attraction of larger ions to the "vapor-liquidlike" interface
      induced by a hydrophobic surface. We propose an analytical model involving a
      modified Poisson-Boltzmann description for the ion density distributions that
      quantitatively predicts the anomalous flow profiles. This description includes as
      a crucial component an ion-size-dependent hydrophobic solvation energy. These
      results provide an effective framework for predicting ion-specific effects, with
      potentially important implications for biological modeling.

PMID- 17501536
TI  - Probing persistence in DNA curvature properties with atomic force microscopy.
AB  - We elaborate on a mean-field extension of the wormlike chain model that accounts
      for the presence of long-range correlations (LRC) in the intrinsic curvature
      disorder of genomic DNA, the stronger the LRC, the smaller the persistence
      length. The comparison of atomic force microscopy imaging of straight,
      uncorrelated virus and correlated human DNA fragments with DNA simulations
      confirms that the observed decrease in persistence length for human DNA more
      likely results from a sequence-induced large-scale intrinsic curvature than from
      some increased flexibility.

PMID- 17501537
TI  - Dynamical evolution of spatiotemporal patterns in mammalian middle cortex.
AB  - The spatiotemporal structure of brain oscillations are important in understanding
      neural function. We analyze oscillatory episodes from isotropic preparations from
      the middle layers of a mammalian cortex which display irregular and chaotic
      spatiotemporal wave activity, within which spontaneously emerge spiral and plane
      waves. The dimensionality of these dynamics shows a consistent decrease during
      the middle of these episodes, regardless of the presence of simple spiral or
      plane waves. It is important to define the relevant biological order parameters
      which govern these dynamical bifurcations.

PMID- 17501541
TI  - Comment on "photoexcitation of a volume plasmon in C60 ions".

PMID- 17501545
TI  - Phase-sensitive recombination of two bose-einstein condensates on an atom chip.
AB  - The recombination of two split Bose-Einstein condensates on an atom chip is shown
      to result in heating which depends on the relative phase of the two condensates.
      This heating reduces the number of condensate atoms between 10% and 40% and
      provides a robust way to read out the phase of an atom interferometer without the
      need for ballistic expansion. The heating may be caused by the dissipation of
      dark solitons created during the merging of the condensates.

PMID- 17501546
TI  - Normal state of highly polarized fermi gases: simple many-body approaches.
AB  - We consider the problem of a single downward arrow atom in the presence of a
      Fermi sea of upward arrow atoms, in the vicinity of a Feshbach resonance. We
      calculate the chemical potential and the effective mass of the downward arrow
      atom using two simple approaches: a many-body variational wave function and a T
      matrix approximation. These two methods lead to the same results and are in good
      agreement with existing quantum Monte Carlo calculations performed at unitarity
      and, in one dimension, with the known exact solution. Surprisingly, our results
      suggest that, even at unitarity, the effect of interactions is fairly weak and
      can be accurately described using single particle-hole excitations. We also
      consider the case of unequal masses.

PMID- 17501547
TI  - Modified coulomb law in a strongly magnetized vacuum.
AB  - We study the electric potential of a charge placed in a strong magnetic field
      B>>B(0) approximately 4.4x10(13) G, as modified by the vacuum polarization. In
      such a field the electron Larmour radius is much less than its Compton length. At
      the Larmour distances a scaling law occurs, with the potential determined by a
      magnetic-field-independent function. The scaling regime implies short-range
      interaction, expressed by the Yukawa law. The electromagnetic interaction regains
      its long-range character at distances larger than the Compton length, the
      potential decreasing across B faster than along. Correction to the
      nonrelativistic ground-state energy of a hydrogenlike atom is found. In the limit
      B = infinity, the modified potential becomes the Dirac delta function plus a
      regular background. With this potential the ground-state energy is finite--the
      best pronounced effect of the vacuum polarization.

PMID- 17501548
TI  - Criterion for bosonic superfluidity in an optical lattice.
AB  - We show that the current method of determining superfluidity in optical lattices
      based on a visibly sharp bosonic momentum distribution n(k) can be misleading,
      for even a normal Bose gas can have a similarly sharp n(k). We show that
      superfluidity in a homogeneous system can be detected from the so-called
      visibility (v) of n(k)--that v must be 1 within O(N(-2/3)), where N is the number
      of bosons. We also show that the T=0 visibility of trapped lattice bosons is far
      higher than what is obtained in some current experiments, suggesting strong
      temperature effects and that these states can be normal. These normal states
      allow one to explore the physics in the quantum critical region.

PMID- 17501549
TI  - Robust controlled-NOT gates from almost any interaction.
AB  - There are many cases where the interaction between two qubits is not precisely
      known, but single-qubit operations are available. In this Letter we show how,
      regardless of an incomplete knowledge of the strength or form of the interaction
      between two qubits, it is often possible to construct a controlled-NOT gate which
      has arbitrarily high fidelity. In particular, we show that oscillations in the
      strength of the exchange interaction in solid state Si and Ge structures are
      correctable.

PMID- 17501550
TI  - Realization and characterization of a two-photon four-qubit linear cluster state.
AB  - We report on the experimental realization of a four-qubit linear cluster state
      via two photons entangled both in polarization and linear momentum. This state
      was investigated by performing tomographic measurements and by evaluating an
      entanglement witness. By use of this state we carried out a novel nonlocality
      proof, the so-called "stronger two observer all-versus-nothing" test of quantum
      nonlocality.

PMID- 17501551
TI  - Synchronized independent narrow-band single photons and efficient generation of
      photonic entanglement.
AB  - We create independent, synchronized single-photon sources with built-in quantum
      memory based on two remote cold atomic ensembles. The synchronized single photons
      are used to demonstrate efficient generation of entanglement. The resulting
      entangled photon pairs violate a Bell's inequality by 5 standard deviations. Our
      synchronized single photons with their long coherence time of 25 ns and the
      efficient creation of entanglement serve as an ideal building block for scalable
      linear optical quantum information processing.

PMID- 17501552
TI  - Quench dynamics and nonequilibrium phase diagram of the bose-hubbard model.
AB  - We investigate the time evolution of correlations in the Bose-Hubbard model
      following a quench from the superfluid to the Mott insulator. For large values of
      the final interaction strength the system approaches a distinctly nonequilibrium
      steady state that bears strong memory of the initial conditions. In contrast,
      when the final interaction strength is comparable to the hopping, the
      correlations are rather well approximated by those at thermal equilibrium. The
      existence of two distinct nonequilibrium regimes is surprising given the
      nonintegrability of the Bose-Hubbard model. We relate this phenomenon to the role
      of quasiparticle interactions in the Mott insulator.

PMID- 17501553
TI  - Reverse monte carlo method and its implications for generalized cluster
      algorithms.
AB  - We describe a novel switching algorithm based on a "reverse" Monte Carlo method,
      in which the potential is stochastically modified before the system configuration
      is moved. This new algorithm facilitates a generalized formulation of cluster
      type Monte Carlo methods, and the generalization makes it possible to derive
      cluster algorithms for systems with both discrete and continuous degrees of
      freedom. The roughening transition in the sine-Gordon model has been studied with
      this method, and high-accuracy simulations for system sizes up to 1024(2) were
      carried out to examine the logarithmic divergence of the surface roughness above
      the transition temperature, revealing clear evidence for universal scaling of the
      Kosterlitz-Thouless type.

PMID- 17501554
TI  - Statistics of entropy production in linearized stochastic systems.
AB  - We consider a wide class of linear stochastic problems driven off the equilibrium
      by a multiplicative asymmetric force. The force breaks detailed balance,
      maintained otherwise, thus producing entropy. The large deviation function of the
      entropy production in the system is calculated explicitly. The general result is
      illustrated using an example of a polymer immersed in a gradient flow and subject
      to thermal fluctuations.

PMID- 17501555
TI  - Hydrogenlike highly charged ions for tests of the time independence of
      fundamental constants.
AB  - Hyperfine transitions in the electronic ground state of cold, trapped
      hydrogenlike highly charged ions have attractive features for use as frequency
      standards because the majority of systematic frequency shifts are smaller by
      orders of magnitude compared to many microwave and optical frequency standards.
      Frequency measurements of these transitions hold promise for significantly
      improved laboratory tests of local position invariance of the electron and quark
      masses.

PMID- 17501556
TI  - Constraints on braneworld gravity models from a kinematic limit on the age of the
      black hole XTE J1118+480.
AB  - In braneworld gravity models with a finite anti-de Sitter space (AdS) curvature
      in the extra dimension, the AdS/conformal field theory correspondence leads to a
      prediction for the lifetime of astrophysical black holes that is significantly
      smaller than the Hubble time, for asymptotic curvatures that are consistent with
      current experiments. Using the recent measurements of the position, three
      dimensional spatial velocity, and mass of the black hole XTE J1118+480, I
      calculate a lower limit on its kinematic age of > or =11 Myr (95% confidence).
      This translates into an upper limit for the asymptotic AdS curvature in the extra
      dimensions of <0.08 mm, which significantly improves the limit obtained by table
      top experiments of sub mm gravity.

PMID- 17501557
TI  - Black hole entropy quantization.
AB  - Ever since the pioneering works of Bekenstein and Hawking, black hole entropy has
      been known to have a quantum origin. Furthermore, it has long been argued by
      Bekenstein that entropy should be quantized in discrete (equidistant) steps given
      its identification with horizon area in (semi-)classical general relativity and
      the properties of area as an adiabatic invariant. This lead to the suggestion
      that the black hole area should also be quantized in equidistant steps to account
      for the discrete black hole entropy. Here we shall show that loop quantum
      gravity, in which area is not quantized in equidistant steps, can nevertheless be
      consistent with Bekenstein's equidistant entropy proposal in a subtle way. For
      that we perform a detailed analysis of the number of microstates compatible with
      a given area and show consistency with the Bekenstein framework when an
      oscillatory behavior in the entropy-area relation is properly interpreted.

PMID- 17501558
TI  - Improving the improved action.
AB  - We investigate the construction of improved actions by the Monte Carlo
      renormalization group method in the context of SU(2) gauge theory utilizing
      different decimation procedures and effective actions. We demonstrate that the
      basic self-consistency requirement for correct application of the Monte Carlo
      renormalization group, i.e., that the decimated configurations are equilibrium
      configurations of the adopted form of the effective action, can be achieved only
      by careful fine-tuning of the choice of decimation prescription and/or action.

PMID- 17501559
TI  - Low energy supersymmetry from the heterotic string landscape.
AB  - We study possible correlations between properties of the observable and hidden
      sectors in heterotic string theory. Specifically, we analyze the case of the Z6
      II orbifold compactification which produces a significant number of models with
      the spectrum of the supersymmetric standard model. We find that requiring
      realistic features does affect the hidden sector such that hidden sector gauge
      group factors SU(4) and SO(8) are favored. In the context of gaugino
      condensation, this implies low energy supersymmetry breaking.

PMID- 17501560
TI  - New physics contributions to the lifetime difference in D0-D0 mixing.
AB  - We present the first general analysis of New Physics contributions to the D0
      D[over ](0) lifetime difference (equivalently DeltaGamma(D)). We argue that New
      Physics (NP) contributions to |DeltaC|=1 processes can dominate the lifetime
      difference in the flavor SU(3) limit. We provide several specific examples of
      models that produce sizable effects in DeltaGamma(D) for realistic values of
      light quark masses, even if such NP contributions are undetectable in the current
      round of D0 decay experiments. This makes DeltaGamma(D) a viable observable for
      studies of indirect effects of New Physics.

PMID- 17501564
TI  - Charge density of a positively charged vector boson may be negative.
AB  - The charge density of vector particles, for example W(+/-), may change sign. The
      effect manifests itself even for a free propagation, when the energy of the W
      boson satisfies epsilon>sqrt[2]m and the standing wave is considered. The charge
      density of W also changes sign in a vicinity of a Coulomb center. For an
      arbitrary vector boson (e.g., for spin 1 mesons), this effect depends on the g
      factor. An origin of this surprising effect is traced to the electric quadrupole
      moment and spin-orbit interaction of vector particles; their contributions to the
      current have a polarization nature. The corresponding charge density equals
      rho(Pol)=-inverted Delta . P, where P is an effective polarization vector that
      depends on the quadrupole moment and spin-orbit interaction. This density
      oscillates in space, producing zero contribution to the total charge.

PMID- 17501565
TI  - Anti-de sitter/conformal-field-theory calculation of screening in a hot wind.
AB  - One of the challenges in relating experimental measurements of the suppression in
      the number of J/psi mesons produced in heavy ion collisions to lattice QCD
      calculations is that whereas the lattice calculations treat J/psi mesons at rest,
      in a heavy ion collision a cc[over ] pair can have a significant velocity with
      respect to the hot fluid produced in the collision. The putative J/psi finds
      itself in a hot wind. We present the first rigorous nonperturbative calculation
      of the consequences of a wind velocity v on the screening length L(s) for a heavy
      quark-antiquark pair in hot N=4 supersymmetric QCD. We find L(s)(v,T)=f(v)[1
      v(2)](1/4)/piT with f(v) only mildly dependent on v and the wind direction. This
      L(s)(v,T) approximately L(s)(0,T)/sqrt[gamma] velocity scaling, if realized in
      QCD, provides a significant additional source of J/psi suppression at transverse
      momenta which are high but within experimental reach.

PMID- 17501566
TI  - Recoil-proton polarization in high-energy deuteron photodisintegration with
      circularly polarized photons.
AB  - We measured the angular dependence of the three recoil-proton polarization
      components in two-body photodisintegration of the deuteron at a photon energy of
      2 GeV. These new data provide a benchmark for calculations based on quantum
      chromodynamics. Two of the five existing models have made predictions of
      polarization observables. Both explain the longitudinal polarization transfer
      satisfactorily. Transverse polarizations are not well described, but suggest
      isovector dominance.

PMID- 17501567
TI  - Measurement of tensor analyzing powers in deuteron photodisintegration.
AB  - A new accurate measurement of the tensor analyzing powers T20, T21, and T22 in
      deuteron photodisintegration has been performed. Wide-aperture nonmagnetic
      detectors allowed broad kinematic coverage in a single set up: E(gamma)=25 to 600
      MeV, and theta(p)(cm)=24 degrees to 48 degrees and 70 degrees to 102 degrees .
      The new data provide a significant improvement over the few existing
      measurements. The angular dependency of the tensor asymmetries in deuteron
      photodisintegration is extracted for the first time.

PMID- 17501563
TI  - Observation of B decays to two kaons.
AB  - Using 449x10(6) BB[over ] pairs collected with the Belle detector at the KEKB
      asymmetric-energy e(+)e(-) collider, we observe clear signals for B(+)-->K[over
      ](0)K(+) and B(0)-->K[over ](0)K(0) decays with 5.3sigma and 6.0sigma
      significance, respectively. We measure the branching fractions B(B(+)-->K[over
      ](0)K(+))=(1.22(-0.28-0.16)(+0.32+0.13))x10(-6) and B(B(0)-->K[over
      ](0)K(0))=(0.87(-0.20)(+0.25)+/-0.09)x10(-6), and partial-rate asymmetries
      A(CP)(B(+)-->K[over ](0)K(+))=0.13(-0.24)(+0.23)+/-0.02 and A(CP)(B(0)-->K[over
      ](0)K(0))=-0.58(-0.66)(+0.73)+/-0.04. From a simultaneous fit, we also obtain
      B(B(+)-->K(0)pi(+))=(22.8(-0.7)(+0.8)+/-1.3)x10(-6) and A(CP)(B(+)-
      >K(0)pi(+))=0.03+/-0.03+/-0.01. The first and second error in the branching
      fractions and the partial-rate asymmetries are statistical and systematic,
      respectively. No signal is observed for B(0)-->K(+)K(-) decays, and for this
      branching fraction, we set an upper limit of 4.1x10(-7) at the 90% confidence
      level.

PMID- 17501568
TI  - Spectral convexity for attractive SU(2N) fermions.
AB  - We prove a general theorem on spectral convexity with respect to particle number
      for 2N degenerate components of fermions. The number of spatial dimensions is
      arbitrary, and the system may be uniform or constrained by an external potential.
      We assume only that the interactions are governed by an SU(2N)-invariant two-body
      potential whose Fourier transform is negative definite. The convexity result
      implies that the ground state is in a 2N-particle clustering phase. We discuss
      implications for light nuclei as well as asymmetric nuclear matter in neutron
      stars.

PMID- 17501569
TI  - Soft x-ray laser spectroscopy on trapped highly charged ions at FLASH.
AB  - In a proof-of-principle experiment, we demonstrate high-resolution resonant laser
      excitation in the soft x-ray region at 48.6 eV of the 2 (2)S(1/2) to 2 (2)P(1/2)
      transition of Li-like Fe23+ ions trapped in an electron beam ion trap by using
      ultrabrilliant light from Free Electron Laser in Hamburg (FLASH). High precision
      spectroscopic studies of highly charged ions at this and upcoming x-ray lasers
      with an expected accuracy gain up to a factor of a thousand, become possible with
      our technique, thus potentially yielding fundamental insights, e.g., into basic
      aspects of QED.

PMID- 17501570
TI  - Double photoionization into double core-hole states in Xe.
AB  - Double photoionization (DPI) leading to double core-hole states of Xe2+ 4d(-2)
      has been studied using a magnetic bottle time-of-flight spectrometer. The
      assignments of the Xe2+ 4d(-2) states are confirmed by the Auger lines extracted
      from fourfold coincidences including two photoelectrons and two Auger electrons.
      It is estimated that the core-core DPI into Xe2+ 4d(-2) at a photon energy of
      301.6 eV has a favored cross section of about 0.3 MB. The intense core-core DPI
      is due to mixing of the 4d(-2) continuum with the 4p single photoionization,
      which is manifested in the relative intensities of the Xe2+ 4d(-2) components.

PMID- 17501571
TI  - Photon correlation versus interference of single-atom fluorescence in a half
      cavity.
AB  - Photon correlations are investigated for a single laser-excited ion trapped in
      front of a mirror. Varying the relative distance between the ion and the mirror,
      photon correlation statistics can be tuned smoothly from an antibunching minimum
      to a bunchinglike maximum. Our analysis concerns the non-Markovian regime of the
      ion-mirror interaction and reveals the field establishment in a half-cavity
      interferometer.

PMID- 17501572
TI  - Spin transfer from an optically pumped alkali vapor to a solid.
AB  - We report enhancement of the spin polarization of 133Cs nuclei in CsH salt by
      spin transfer from an optically pumped cesium vapor. The nuclear polarization was
      4.0 times the equilibrium polarization at 9.4 T and 137 degrees C, with larger
      enhancements at lower fields. This work is the first demonstration of spin
      transfer from a polarized alkali vapor to the nuclei of a solid, opening up new
      possibilities for research in hyperpolarized materials.

PMID- 17501573
TI  - Interplay between magic number stabilities and superfluidity of small
      parahydrogen clusters.
AB  - The interplay between magic number stabilities and superfluidity of small
      parahydrogen clusters with sizes N=5 to 40 and temperatures 0.5 K</=T</=4.5 K is
      explored with classical and quantum path integral Monte Carlo calculations.
      Clusters with N<26 and T</=1.5 K have large superfluid fractions even at the
      stable magic numbers 13, 19, and 23. In larger clusters, superfluidity is
      quenched especially at the magic numbers 26, 29, 32, and 37 while below 1 K,
      superfluidity is recovered for the pairs (27,28), (30,31), and (35,36). For all
      clusters superfluidity is localized at the surface and correlates with long
      exchange cycles involving loosely bound surface molecules.

PMID- 17501574
TI  - Interfacing collective atomic excitations and single photons.
AB  - We study the performance and limitations of a coherent interface between
      collective atomic states and single photons. A quantized spin-wave excitation of
      an atomic sample inside an optical resonator is prepared probabilistically,
      stored, and adiabatically converted on demand into a sub-Poissonian photonic
      excitation of the resonator mode. The measured peak single-quantum conversion
      efficiency of chi=0.84(11) and its dependence on various parameters are well
      described by a simple model of the mode geometry and multilevel atomic structure,
      pointing the way towards implementing high-performance stationary single-photon
      sources.

PMID- 17501575
TI  - Direct observation of a transition of a surface plasmon resonance from a photonic
      crystal effect.
AB  - Transition of surface-plasmon resonance from out-of-plane photonic crystal effect
      is observed in a semiconductor array of subwavelength holes by optical pump
      terahertz probe measurements. The dielectric properties of the photoexcited array
      are essentially altered by the intense optical excitation due to photogenerated
      free carriers. As a result, the array becomes metallic and favors the coupling
      and propagation of surface plasmons. The photoinduced resonant extremes agree
      well with the Fano model.

PMID- 17501576
TI  - Subsurface near-field scanning tomography.
AB  - The scanning tomography method is developed for electromagnetic sounding of a 3D
      structure of an inhomogeneous dielectric half-space. It is shown that known
      methods of physical diagnostics are suitable for this tomography with the depth
      of analysis from nanometers at optical frequencies up to several kilometers at
      ultralow frequencies. The areas of application include nanophysics, biological
      and medical diagnostics, subsurface remote sensing in geophysics and geology,
      etc. This approach is realized in the microwave scanning tomography of living
      tissues where a subwavelength resolution is achieved.

PMID- 17501577
TI  - High harmonic generation and the role of atomic orbital wave functions.
AB  - High harmonic spectra were recorded from different rare-gas atoms under identical
      experimental conditions. It is shown that although each atom's spectrum is
      different, the differences are due almost entirely to the orbital influence in
      the recombination step. The amplitude of the continuum electron wave packet
      versus kinetic energy is derived from these data and is shown to be largely
      independent of the atom, in agreement with models of tunnel ionization. We
      compare the measurements with calculations in both the length gauge and the
      velocity gauge and show that the two gauges imply a different de Broglie
      wavelength.

PMID- 17501578
TI  - Noise-induced synchronization and clustering in ensembles of uncoupled limit
      cycle oscillators.
AB  - We study synchronization properties of general uncoupled limit-cycle oscillators
      driven by common and independent Gaussian white noises. Using phase reduction and
      averaging methods, we analytically derive the stationary distribution of the
      phase difference between oscillators for weak noise intensity. We demonstrate
      that in addition to synchronization, clustering, or more generally coherence,
      always results from arbitrary initial conditions, irrespective of the details of
      the oscillators.

PMID- 17501562
TI  - Measurements of CP-violating asymmetries in B0-->a1+/-(1260)pi-/+ decays.
AB  - We present measurements of CP-violating asymmetries in the decay B(0)-->a(1)(+/
      )(1260)pi(-/+) with a(1)(+/-)(1260)-->pi(-/+)pi(+/-)pi(+/-). The data sample
      corresponds to 384x10(6) BB[over ] pairs collected with the BABAR detector at the
      PEP-II asymmetric B factory at SLAC. We measure the CP-violating asymmetry
      A(CP)(a(1)pi)=-0.07+/-0.07+/-0.02, the mixing-induced CP violation parameter
      S(a(1)pi)=0.37+/-0.21+/-0.07, the direct CP violation parameter C(a(1)pi)=-0.10+/
      0.15+/-0.09, and the parameters DeltaC(a(1)pi)=0.26+/-0.15+/-0.07 and
      DeltaS(a(1)pi)=-0.14+/-0.21+/-0.06. From these measured quantities we determine
      the angle alpha(eff)=78.6 degrees +/-7.3 degrees.

PMID- 17501561
TI  - Evidence for production of single top quarks and first direct measurement of
      |Vtb|.
AB  - The D0 Collaboration presents first evidence for the production of single top
      quarks at the Fermilab Tevatron pp[over ] collider. Using a 0.9 fb(-1) dataset,
      we apply a multivariate analysis to separate signal from background and measure
      sigma(pp[over ]-->tb+X,tqb+X)=4.9+/-1.4 pb. The probability to measure a cross
      section at this value or higher in the absence of a signal is 0.035%,
      corresponding to a 3.4 standard deviation significance. We use the cross section
      measurement to directly determine the Cabibbo-Kobayashi-Maskawa matrix element
      that describes the Wtb coupling and find 0.68<|V(tb)|</=1 at 95% C.L. within the
      standard model.

PMID- 17501579
TI  - Fano blockade by a bose-einstein condensate in an optical lattice.
AB  - We study the transport of atoms across a localized Bose-Einstein condensate in a
      one-dimensional optical lattice. For atoms scattering off the condensate, we
      predict total reflection as well as full transmission for certain parameter
      values on the basis of an exactly solvable model. The findings of analytical and
      numerical calculations are interpreted by a tunable Fano-like resonance and may
      lead to interesting applications for blocking and filtering atom beams.

PMID- 17501580
TI  - Equilibration and universal heat conduction in fermi-pasta-ulam chains.
AB  - It is shown numerically that for Fermi-Pasta-Ulam (FPU) chains with alternating
      masses and heat baths at slightly different temperatures at the ends, the local
      temperature (LT) on small scales behaves paradoxically in steady state. This
      expands the long established problem of equilibration of FPU chains. A well
      behaved LT appears to be achieved for equal mass chains; the thermal conductivity
      is shown to diverge with chain length N as N(1/3), relevant for the much debated
      question of the universality of one-dimensional heat conduction. The reason why
      earlier simulations have obtained systematically higher exponents is explained.

PMID- 17501581
TI  - Proposal for a quantum-degenerate electron source.
AB  - We propose a pulsed electron source capable of 6D brightness orders-of-magnitude
      greater than that of existing sources. It could deliver average current up to 0.5
      pA and achieve an emittance approaching the quantum limit in each spatial
      dimension. It could be employed to advantage in electron microscopy, inverse
      photo-emission, precision low-energy scattering experiments, and electron
      holography. This source could make possible pump-probe experiments with Angstrom
      spatial and subpicosecond time resolution. Here, we present the basic concepts of
      the source, including a generalized expression for the brightness that can be
      used in the quantum limited case and the analysis of the main issues that must be
      addressed for successful construction and operation. We have begun an experiment
      to demonstrate its essential features.

PMID- 17501582
TI  - Enhanced ductile behavior of tensile-elongated individual double-walled and
      triple-walled carbon nanotubes at high temperatures.
AB  - We report exceptional ductile behavior in individual double-walled and triple
      walled carbon nanotubes at temperatures above 2000 degrees C, with tensile
      elongation of 190% and diameter reduction of 90%, during in situ tensile-loading
      experiments conducted inside a high-resolution transmission electron microscope.
      Concurrent atomic-scale microstructure observations reveal that the
      superelongation is attributed to a high temperature creep deformation mechanism
      mediated by atom or vacancy diffusion, dislocation climb, and kink motion at high
      temperatures. The superelongation in double-walled and triple-walled carbon
      nanotubes, the creep deformation mechanism, and dislocation climb in carbon
      nanotubes are reported here for the first time.

PMID- 17501584
TI  - Surface nucleation in the freezing of gold nanoparticles.
AB  - We use molecular simulation to calculate the nucleation free energy barrier for
      the freezing of a 456 atom gold cluster over a range of temperatures. The results
      show that the embryo of the solid cluster grows at the vapor-surface interface
      for all temperatures studied and that the usual classical nucleation model, with
      the embryo growing in the core of the cluster, is unable to predict the shape of
      the free energy barrier. We use a simple partial wetting model that treats the
      crystal as a lens-shaped nucleus at the liquid-vapor interface and find that the
      line tension plays an important role in the freezing of gold nanoparticles.

PMID- 17501583
TI  - Density-wave theory of the capsid structure of small icosahedral viruses.
AB  - We apply Landau theory of crystallization to explain and to classify the capsid
      structures of small viruses with spherical topology and icosahedral symmetry. We
      develop an explicit method which predicts the positions of centers of mass for
      the proteins constituting the viral capsid shell. Corresponding density
      distribution function which generates the positions has a universal form without
      any fitting parameter. The theory describes in a uniform way both the structures
      satisfying the well-known Caspar and Klug geometrical model for capsid
      construction and those violating it.

PMID- 17501585
TI  - Medium-range fluctuations accompanying the metal-nonmetal transition in expanded
      fluid hg.
AB  - We have carried out small angle x-ray scattering experiments of expanded fluid Hg
      in the metal-nonmetal (M-NM) transition region around 9.0 g cm(-3). Increase of
      small angle scattering intensity following the Ornstein-Zernike equation is
      clearly observed in the M-NM transition region as well as near the liquid-vapor
      critical point at 5.8 g cm(-3). The short-range correlation length, R, becomes
      twice as large in the M-NM transition region as in the critical region. The
      enhancement of R in expanded fluid Hg suggests a new type of fluctuations
      reflecting a first-order M-NM transition.

PMID- 17501586
TI  - Evaluation of the disorder temperature and free-volume formalisms via simulations
      of shear banding in amorphous solids.
AB  - Molecular dynamics simulations of shear band development over 1000% strain in
      simple shear are used to test whether the local plastic strain rate is
      proportional to exp(-1/chi), where chi is a dimensionless quantity related to the
      disorder temperature or free volume that characterizes the structural state of
      the glass. Scaling is observed under the assumption that chi is linearly related
      to the local potential energy per atom. We calculate the potential energy per
      atom corresponding to absolute zero disorder temperature and the energy needed to
      create a shear transformation zone.

PMID- 17501587
TI  - Particle dynamics in polymer-metal nanocomposite thin films on nanometer-length
      scales.
AB  - X-ray photon correlation spectroscopy was used in conjunction with resonance
      enhanced grazing-incidence small-angle x-ray scattering to probe slow particle
      dynamics and kinetics in gold/polystyrene nanocomposite thin films. Such enhanced
      coherent scattering enables, for the first time, measurement of the particle
      dynamics at wave vectors up to approximately 1 nm(-1) (or a few nanometers
      spatially) in a disordered system, well in the regime where entanglement,
      confinement, and particle interaction dominate the dynamics and kinetics.
      Measurements of the intermediate structure factor f(q,t) indicate that the
      particle dynamics differ from Stokes-Einstein Brownian motion and are explained
      in terms of viscoelastic effects and interparticle interactions.

PMID- 17501588
TI  - Fluctuations and phase separation in a quasi-one-dimensional system.
AB  - Phase transitions in a quasi-one-dimensional surface system on a metal substrate
      are investigated as a function of temperature. Upon cooling the system shows a
      loss of long-range order, fluctuations, and a transition into an inhomogeneous
      ground state due to competition of local adsorbate-adsorbate interactions with an
      incommensurate charge density wave. This agrees with a general phase diagram for
      correlated systems and high-temperature superconductors. The model surface system
      allows direct imaging of the fluctuations and the glassy inhomogeneous ground
      state by scanning tunneling microscopy.

PMID- 17501589
TI  - Growth of one-dimensional Pd nanowires on the terraces of a reduced SnO2(101)
      surface.
AB  - Palladium, vapor-deposited at room temperature on a reduced SnO2(101) surface,
      forms one-dimensional islands, one atomic layer high, 5 A wide, and up to 350 A
      long. Scanning tunneling microscopy shows that neighboring islands do not merge.
      First-principles calculations reveal the atomistic processes that lead to this,
      for metal oxide substrates unusual, overlayer growth. Formation of 1D islands is
      mediated by a large anisotropy in surface diffusion, strong Pd-Sn interaction,
      and the lack of stable binding sites at the sides of the Pd islands. Nucleation
      is defect mediated, and the initial nucleation site determines the width of the
      resulting nanocluster.

PMID- 17501590
TI  - Effect of measurement probes upon the conductance of an interacting nanosystem:
      detection of an attached ring by nonlocal many body effects.
AB  - We consider a nanosystem connected to measurement probes via leads. When a
      magnetic flux is varied through a ring attached to one lead at a distance L(c)
      from the nanosystem, the effective nanosystem transmission |t(s)|(2) exhibits
      Aharonov-Bohm oscillations if the electrons interact inside the nanosystem. These
      oscillations can be very large if L(c) is small and if the nanosystem has almost
      degenerate levels which are put near the Fermi energy by a local gate.

PMID- 17501591
TI  - Absolute negative resistance induced by directional electron-electron scattering
      in a two-dimensional electron gas.
AB  - A three-terminal device formed by two electrostatic barriers crossing an
      asymmetrically patterned two-dimensional electron gas displays an unusual
      potential depression at the middle contact, yielding absolute negative
      resistance. The device displays momentum and current transfer ratios that far
      exceed unity. The observed reversal of the current or potential in the middle
      terminal can be interpreted as the analog of Bernoulli's effect in a Fermi
      liquid. The results are explained by directional scattering of electrons in two
      dimensions.

PMID- 17501592
TI  - Mesoscopic to universal crossover of the transmission phase of multilevel quantum
      dots.
AB  - Transmission phase alpha measurements of many-electron quantum dots (small mean
      level spacing delta) revealed universal phase lapses by pi between consecutive
      resonances. In contrast, for dots with only a few electrons (large delta), the
      appearance or not of a phase lapse depends on the dot parameters. We show that a
      model of a multilevel quantum dot with local Coulomb interactions and arbitrary
      level-lead couplings reproduces the generic features of the observed behavior.
      The universal behavior of alpha for small delta follows from Fano-type
      antiresonances of the renormalized single-particle levels.

PMID- 17501593
TI  - Fock-Darwin states of dirac electrons in graphene-based artificial atoms.
AB  - We investigate the Fock-Darwin states of the massless chiral fermions confined in
      a graphitic parabolic quantum dot. In light of Klein tunneling, we analyze the
      condition for confinement of the Dirac fermions in a cylindrically symmetric
      potential. New features of the energy levels of the Dirac electrons as compared
      to the conventional electronic systems are discussed. We also evaluate the dipole
      allowed transitions in the energy levels of the dots. We propose that in the high
      magnetic field limit, the band parameters can be accurately determined from the
      dipole-allowed transitions.

PMID- 17501594
TI  - Room-temperature electron spin dynamics in free-standing ZnO quantum dots.
AB  - Conduction band electrons in colloidal ZnO quantum dots have been prepared
      photochemically and examined by electron paramagnetic resonance spectroscopy.
      Nanocrystals of 4.6 nm diameter containing single S-shell conduction band
      electrons have g(*)=1.962 and a room-temperature ensemble spin-dephasing time of
      T(2)(*)=25 ns, as determined from linewidth analysis. Increasing the electron
      population leads to increased g(*) and decreased T(2)(*), both associated with
      formation of P-shell configurations. A clear relationship between T(2)(*) and
      hyperfine coupling with 67Zn(I=5/2) is observed.

PMID- 17501595
TI  - Correlation-induced resonances and population switching in a quantum-dot coulomb
      valley.
AB  - Strong correlation effects on electron transport through a spinless quantum dot
      are considered. When two single-particle levels in the quantum dot are
      degenerate, a conserved pseudospin degree of freedom appears for generic
      tunneling matrix elements between the quantum dot and leads. Local fluctuations
      of the pseudospin in the quantum dot give rise to a pair of asymmetric
      conductance peaks near the center of a Coulomb valley. An exact relation to the
      population switching is provided.

PMID- 17501596
TI  - Carrier transport in two-dimensional graphene layers.
AB  - Carrier transport in gated 2D graphene monolayers is considered in the presence
      of scattering by random charged impurity centers with density n(i). Excellent
      quantitative agreement is obtained (for carrier density n>10(12) cm(-2)) with
      existing experimental data. The conductivity scales linearly with n/n(i) in the
      theory. We explain the experimentally observed asymmetry between electron and
      hole conductivities, and the high-density saturation of conductivity for the
      highest mobility samples. We argue that the experimentally observed saturation of
      conductivity at low density arises from the charged impurity induced
      inhomogeneity in the graphene carrier density which becomes severe for n less,
      similarn(i) approximately 10(12) cm(-2).

PMID- 17501597
TI  - Giant spin splitting through surface alloying.
AB  - The long-range ordered surface alloy Bi/Ag(111) is found to exhibit a giant spin
      splitting of its surface electronic structure due to spin-orbit coupling, as is
      determined by angle-resolved photoelectron spectroscopy. First-principles
      electronic structure calculations fully confirm the experimental findings. The
      effect is brought about by a strong in-plane gradient of the crystal potential in
      the surface layer, in interplay with the structural asymmetry due to the surface
      potential barrier. As a result, the spin polarization of the surface states is
      considerably rotated out of the surface plane.

PMID- 17501598
TI  - Scaling of resistance and electron mean free path of single-walled carbon
      nanotubes.
AB  - We present an experimental investigation on the scaling of resistance in
      individual single-walled carbon nanotube devices with channel lengths that vary 4
      orders of magnitude on the same sample. The electron mean free path is obtained
      from the linear scaling of resistance with length at various temperatures. The
      low temperature mean free path is determined by impurity scattering, while at
      high temperature, the mean free path decreases with increasing temperature,
      indicating that it is limited by electron-phonon scattering. An unusually long
      mean free path at room temperature has been experimentally confirmed.
      Exponentially increasing resistance with length at extremely long length scales
      suggests anomalous localization effects.

PMID- 17501599
TI  - Electron fractionalization in two-dimensional graphenelike structures.
AB  - Electron fractionalization is intimately related to topology. In one-dimensional
      systems, fractionally charged states exist at domain walls between degenerate
      vacua. In two-dimensional systems, fractionalization exists in quantum Hall
      fluids, where time-reversal symmetry is broken by a large external magnetic
      field. Recently, there has been a tremendous effort in the search for examples of
      fractionalization in two-dimensional systems with time-reversal symmetry. In this
      Letter, we show that fractionally charged topological excitations exist on
      graphenelike structures, where quasiparticles are described by two flavors of
      Dirac fermions and time-reversal symmetry is respected. The topological zero
      modes are mathematically similar to fractional vortices in p-wave
      superconductors. They correspond to a twist in the phase in the mass of the Dirac
      fermions, akin to cosmic strings in particle physics.

PMID- 17501600
TI  - Fermi-edge singularity of spin-polarized electrons.
AB  - We study the absorption spectrum of a two-dimensional electron gas (2DEG) in a
      magnetic field. We find that at low temperatures, when the 2DEG is spin
      polarized, the absorption spectra, which correspond to the creation of spin up or
      spin down electrons, differ in magnitude, linewidth, and filling factor
      dependence. We show that these differences can be explained as resulting from the
      creation of a Mahan exciton in one case, and of a power law Fermi-edge
      singularity in the other.

PMID- 17501601
TI  - Sharp superconductor-insulator transition in short wires.
AB  - Recent experiments on short MoGe nanowires show a sharp superconducting
      insulating transition at the universal resistance R(Q)=h/(4e(2)), contrary to the
      expectation of a smooth temperature dependence of the resistance for such
      Josephson-like systems. We present a self-consistent renormalization-group
      treatment of interacting quantum phase slips in short superconducting wires,
      which reproduces this sharp universal transition. Our method should also apply to
      other systems in the sine-Gordon universality class, in the previously
      inaccessible intermediate-coupling regime.

PMID- 17501602
TI  - Elasticity and melting of skyrmion flux lattices in p-wave superconductors.
AB  - We analytically calculate the energy, magnetization curves [B(H)], and elasticity
      of Skyrmions flux lattices in p-wave superconductors near the lower critical
      field H(c1), and we use these results with the Lindemann criterion to predict
      their melting curve. In striking contrast to vortex flux lattices, which always
      melt at an external field H>H(c1), Skyrmion flux lattices never melt near H(c1).
      This provides a simple and unambiguous test for the presence of Skyrmions.

PMID- 17501603
TI  - Enhanced charge gap in the bilayer manganite La2-2xSr1+2xMn2O7 near x = 0.4.
AB  - We have investigated the optical conductivity spectra of La2-2xSr1+2xMn2O7
      (0.3</=x</=0.5) systematically and found that for x near 0.4 the charge gap shows
      enhancement of up to approximately 0.3 eV just above the long-range magnetic
      ordering temperature. From comparison of this charge gap with other experimental
      results, we conclude that the peculiar x dependence of the charge gap cannot be
      understood in terms of the charge and lattice correlations only. We suggest that
      the unusual enhancement originates from the cooperative coupling between the
      short-range charge or lattice correlations and the quasi-one-dimensional energy
      band near the Fermi level.

PMID- 17501604
TI  - Direct imaging of stochastic domain-wall motion driven by nanosecond current
      pulses.
AB  - Magnetic transmission x-ray microscopy is used to directly visualize the
      influence of a spin-polarized current on domain walls in curved permalloy wires.
      Pulses of nanosecond duration and of high current density up to 1.0x10(12) A/m(2)
      are used to move and to deform the domain wall. The current pulse drives the wall
      either undisturbed, i.e., as composite particle through the wire, or causes
      structural changes of the magnetization. Repetitive pulse measurements reveal the
      stochastic nature of current-induced domain-wall motion.

PMID- 17501605
TI  - g-factor tuning and manipulation of spins by an electric current.
AB  - We investigate the Zeeman splitting of the two-dimensional electron gas in an
      asymmetric silicon quantum well, performing electron-spin-resonance (ESR)
      experiments. Applying a small dc current we observe a shift in the resonance
      field due to the additional current-induced Bychkov-Rashba type of spin-orbit
      field. We also show that a high frequency current may induce electric dipole spin
      resonance very efficiently. We identify different contributions to this type of
      ESR signal.

PMID- 17501606
TI  - pi-electron ferromagnetism in metal-free carbon probed by soft x-ray dichroism.
AB  - Elemental carbon represents a fundamental building block of matter and the
      possibility of ferromagnetic order in carbon has attracted widespread attention.
      However, the origin of magnetic order in such a light element is only poorly
      understood and has puzzled researchers. We present a spectromicroscopy study at
      room temperature of proton irradiated metal-free carbon using the elemental and
      chemical specificity of x-ray magnetic circular dichroism. We demonstrate that
      the magnetic order in the investigated system originates only from the carbon pi
      electron system.

PMID- 17501607
TI  - Exciton dephasing in quantum dots due to LO-phonon coupling: an exactly solvable
      model.
AB  - It is widely believed that, due to its discrete nature, excitonic states in a
      quantum dot coupled to dispersionless longitudinal-optical (LO) phonons form
      everlasting mixed states (exciton polarons) showing no line broadening in the
      spectrum. This is indeed true if the model is restricted to a limited number of
      excitonic states in a quantum dot. We show, however, that extending the model to
      a large number of states results in LO phonon-induced spectral broadening and
      complete decoherence of the optical response.

PMID- 17501608
TI  - Experimental observation of different-order components of a vibrational wave
      packet in a bulk dielectric using high-order Raman scattering.
AB  - We use high-order Raman scattering in a bulk dielectric to characterize coherent
      dynamics with precision typical for gas phase experiments. The experimental pump
      probe approach allows for the simultaneous observation and separation in space
      and time of the individual contributions of different-order Raman processes to a
      coherent wave packet without relying on phase-matching conditions and within the
      same experimental geometry. We propose a novel technique to discriminate between
      stimulated excitation of vibronic levels in the impulsive and intermediate
      excitation regimes, futhermore allowing us to distinguish between different
      pathways contributing to the same fifth-order Raman processes.

PMID- 17501609
TI  - Mosaic multistate scenario versus one-state description of supercooled liquids.
AB  - According to the mosaic scenario, relaxation in supercooled liquids is ruled by
      two competing mechanisms: surface tension, opposing the creation of local
      excitations, and entropy, providing the drive to the configurational
      rearrangement of a given region. We test this scenario through numerical
      simulations well below the Mode Coupling temperature. For an equilibrated
      configuration, we freeze all the particles outside a sphere and study the
      thermodynamics of this sphere. The frozen environment acts as a pinning field.
      Measuring the overlap between the unpinned and pinned equilibrium configurations
      of the sphere, we can see whether it has switched to a different state. We do not
      find any clear evidence of the mosaic scenario. Rather, our results seem
      compatible with the existence of a single (liquid) state. However, we find
      evidence of a growing static correlation length, apparently unrelated to the
      mosaic one.

PMID- 17501610
TI  - Evolution of growth modes for polyelectrolyte bundles.
AB  - Multivalent ions induce attractions between polyelectrolytes, but lead to finite
      sized bundles rather than macroscopic phase separation. The kinetics of
      aggregation and bundle formation of actin is tracked using two different
      fluorescently labeled populations of F-actin. It is found that the growth mode of
      these bundles evolves with time and salt concentration, varying from an initial
      lateral growth to a longitudinal one at later stages. The results suggest that
      kinetics play a role in bundle growth, but not in the lateral size of bundles,
      which is constant for linear and branched topologies.

PMID- 17501611
TI  - Surface-groove-induced azimuthal anchoring of a nematic liquid crystal:
      Berreman's model reexamined.
AB  - To account for azimuthal surface anchoring of a nematic liquid crystal, Berreman
      [Phys. Rev. Lett. 28, 1683 (1972)10.1103/PhysRevLett.28.1683] proposed a simple
      model attributing the surface anchoring to the elastic distortion of the liquid
      crystal induced by the grooves of a surface. He showed that the surface anchoring
      energy is proportional to sin(2)varphi, with varphi being the angle between the
      director at infinity and the direction of the surface grooves. We argue that his
      assumption of negligibly small azimuthal distortion of the nematic is not valid.
      Proper treatment of the azimuthal distortion reveals that the Berreman's model
      should yield a surface anchoring energy proportional to sin(4)varphi. This
      implies that surface grooves alone cannot contribute to the surface anchoring
      coefficient in the usual Rapini-Papoular sense.

PMID- 17501612
TI  - Why do active and stabilized dunes coexist under the same climatic conditions?
AB  - Sand dunes can be active (mobile) or stable, mainly as a function of vegetation
      cover and wind power. However, there exists as yet unexplained evidence for the
      coexistence of bare mobile dunes and vegetated stabilized dunes under the same
      climatic conditions. We propose a model for dune vegetation cover driven by wind
      power that exhibits bistabilty and hysteresis with respect to the wind power. For
      intermediate wind power, mobile and stabilized dunes can coexist, whereas for low
      (or high) wind power they can be fixed (or mobile). Climatic change or human
      intervention can turn active dunes into stable ones and vice versa; our model
      predicts that prolonged droughts with stronger winds can result in dune
      reactivation.

PMID- 17501613
TI  - Caging dynamics in a granular fluid.
AB  - We report an experimental investigation of the caging motion in a uniformly
      heated granular fluid for a wide range of filling fractions, varphi. At low
      varphi the classic diffusive behavior of a fluid is observed. However, as varphi
      is increased, temporary cages develop and particles become increasingly trapped
      by their neighbors. We statistically analyze particle trajectories and observe a
      number of robust features typically associated with dense molecular liquids and
      colloids. Even though our monodisperse and quasi-2D system is known to not
      exhibit a glass transition, we still observe many of the precursors usually
      associated with glassy dynamics. We speculate that this is due to a process of
      structural arrest provided, in our case, by the presence of crystallization.

PMID- 17501614
TI  - Swinging of red blood cells under shear flow.
AB  - We reveal that under moderate shear stress (etagamma[over ] approximately 0.1 Pa)
      red blood cells present an oscillation of their inclination (swinging)
      superimposed to the long-observed steady tank treading (TT) motion. A model based
      on a fluid ellipsoid surrounded by a viscoelastic membrane initially unstrained
      (shape memory) predicts all observed features of the motion: an increase of both
      swinging amplitude and period (1/2 the TT period) upon decreasing etagamma[over
      ], a etagamma[over ]-triggered transition toward a narrow etagamma[over ] range
      intermittent regime of successive swinging and tumbling, and a pure tumbling at
      low etagamma[over ] values.

PMID- 17501615
TI  - Spot deformation and replication in the two-dimensional Belousov-Zhabotinski
      reaction in a water-in-oil microemulsion.
AB  - In the limit of a large duffusivity ratio, spotlike solutions in the two
      dimensional Belousov-Zhabotinski reaction in water-in-oil microemulsion are
      studied. It is shown analytically that such spots undergo an instability as the
      diffusivity ratio is decreased. An instability threshold is derived. For spots of
      small radius, it is shown that this instability leads to a spot splitting into
      precisely two spots. For larger spots, it leads to deformation, fingering
      patterns, and space-filling curves. Numerical simulations are shown to be in
      close agreement with the analytical predictions.

PMID- 17501616
TI  - Nonequilibrium sedimentation of colloids on the particle scale.
AB  - We investigate sedimentation of model hard-sphere-like colloidal dispersions
      confined in horizontal capillaries using laser scanning confocal microscopy,
      dynamical density functional theory, and Brownian dynamics computer simulations.
      For homogenized initial states we obtain quantitative agreement of the results
      from the respective approaches for the time evolution of the one-body density
      distribution and the osmotic pressure on the walls. We demonstrate that single
      particle information can be obtained experimentally in systems that were
      initialized further out of equilibrium such that complex lateral patterns form.

PMID- 17501617
TI  - Comment on "direct measurement of the oscillation frequency in an optical
      tweezers trap by parametric excitation".

PMID- 17501618
TI  - Comment on "direct measurement of the oscillation frequency in an optical
      tweezers trap by parametric excitation".

PMID- 17501623
TI  - Cyclin D1 as a target for the proliferative effects of PTH and PTHrP in early
      osteoblastic cells.
AB  - PTHrP induced a proliferative cyclin D1 activation in low-density osteoblastic
      cells. The process was PKA and MAPK dependent and involved both AP-1 and CRE
      sites. In ectopic ossicles generated from implanted bone marrow stromal cells,
      PTH upregulated cyclin D1 after acute or intermittent anabolic treatment. These
      data suggest a positive role of PTH and PTHrP in the cell cycle of early
      osteoblasts. INTRODUCTION: The mechanisms underlying the actions of PTH and its
      related protein (PTHrP) in osteoblast proliferation, differentiation, and bone
      remodeling remain unclear. The action of PTH or PTHrP on the cell cycle during
      osteoblast proliferation was studied. MATERIALS AND METHODS: Mouse calvarial
      MC3T3-E1 clone 4 cells were synchronized by serum starvation and induced with 100
      nM PTHrP for 2-24 h under defined low serum conditions. Western blot, real-time
      PCR, EMSAs, and promoter/luciferase assays were performed to evaluate cyclin D1
      expression. Pharmacological inhibitors were used to determine the relevant
      signaling pathways. Ectopic ossicles generated from implanted bone marrow stromal
      cells were treated with acute (a single 8- or 12-h injection) or intermittent
      anabolic PTH treatment for 7 days, and RNA and histologic analysis were
      performed. RESULTS: PTHrP upregulated cyclin D1 and CDK1 and decreased p27
      expression. Cyclin D1 promoter/luciferase assays showed that the PTHrP regulation
      involved both activator protein-1 (AP-1) and cyclic AMP response element binding
      protein (CRE) sites. AP-1 and CRE double mutants completely abolished the PTHrP
      effect of cyclin D1 transcription. Upregulation of cyclin D1 was found to be
      protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) dependent in
      proliferating MC3T3-E1 cells. In vivo expression of cyclin D1 in ectopic ossicles
      was upregulated after a single 12-h PTH injection or intermittent anabolic PTH
      treatment for 7 days in early developing ossicles. CONCLUSIONS: These data
      indicate that PTH and PTHrP induce cyclin D1 expression in early osteoblastic
      cells and their action is developmental stage specific.

PMID- 17501624
TI  - Bone remodeling rate and remodeling balance are not co-regulated in adulthood:
      implications for the use of activation frequency as an index of remodeling rate.
AB  - Use of activation frequency as a measure of remodeling rate assumes co-regulation
      of remodeling rate and remodeling balance. In iliac crest biopsy specimens from
      57 healthy subjects 19-80 yr of age, no correlations were shown between these
      variables, an observation that challenges the use of activation frequency as an
      estimate of remodeling rate. INTRODUCTION: The histomorphometric derivation of
      activation frequency assumes that the remodeling rate is dependent on the
      duration of the remodeling cycle and the amount of bone formed in individual
      remodeling units. This implies that remodeling balance and remodeling rate are co
      regulated. We tested this assumption in normal human adult cancellous bone.
      MATERIALS AND METHODS: Relationships between indices of bone formation at the
      basic multicellular unit (BMU) level (wall width and mineral apposition rate) and
      indices of remodeling rate (mineralizing perimeter and osteoid perimeter) were
      examined in iliac crest biopsies obtained from 57 healthy adults (24 men) 19-80
      yr of age. RESULTS: Univariate analysis revealed a negative correlation between
      wall width and osteoid perimeter (r = -0.38; p = 0.0004), but there was no
      correlation between wall width and mineralizing perimeter or between mineral
      apposition rate and either mineralizing or osteoid perimeter. After adjustment
      for age and sex, the association between wall width and osteoid perimeter was no
      longer observed. Both wall width and mineral apposition rate correlated
      negatively with age (r = -0.75, p < 0.0001 and r = -0.27, p = 0.05,
      respectively). CONCLUSIONS: Our results indicate that remodeling balance and
      remodeling rate are not co-regulated in adult human bone. Activation frequency,
      as currently derived from histomorphometric variables, may therefore be
      unreliable as an indicator of remodeling rate.

PMID- 17501625
TI  - Construction of the femoral neck during growth determines its strength in old
      age.
AB  - Study of the design of the FN in vivo in 697 women and in vitro in 200 cross
      sections of different sizes and shapes along each of 13 FN specimens revealed
      that strength in old age was largely achieved during growth by differences in the
      distribution rather than the amount of bone material in a given FN cross-section
      from individual to individual. INTRODUCTION: We studied the design of the femoral
      neck (FN) to gain insight into the structural basis of FN strength in adulthood
      and FN fragility in old age. MATERIALS AND METHODS: Studies in vivo were
      performed using densitometry in 697 women and in vitro using high-resolution
      microCT and direct measurements in 13 pairs of postmortem specimens. RESULTS: The
      contradictory needs of strength for loading yet lightness for mobility were met
      by varying FN size, shape, spatial distribution, and proportions of its
      trabecular and cortical bone in a cross-section, not its mass. Wider and narrower
      FNs were constructed with similar amounts of bone material. Wider FNs were
      relatively lighter: a 1 SD higher FN volume had a 0.67 (95% CI, 0.61-0.72) SD
      lower volumetric BMD (vBMD). A 1 SD increment in height was achieved by
      increasing FN volume by 0.32 (95% CI, 0.25-0.39) SD with only 0.15 (95% CI, 0.08
      0.22) SD more bone, so taller individuals had a relatively lighter FN (vBMD was
      0.13 [95% CI, 0.05-0.20 SD] SD lower). Greater periosteal apposition constructing
      a wider FN was offset by even greater endocortical resorption so that the same
      net amount of bone was distributed as a thinner cortex further from the neutral
      axis, increasing resistance to bending and lowering vBMD. This was recapitulated
      at each point along the FN; varying absolute and relative degrees of periosteal
      apposition and endocortical resorption focally used the same amount of material
      to fashion an elliptical FN of mainly cortical bone near the femoral shaft to
      offset bending but a more circular FN of proportionally more trabecular and less
      cortical bone to accommodate compressive loads adjacent to the pelvis. This
      structural heterogeneity was largely achieved by adaptive modeling and remodeling
      during growth-most of the variance in FN volume, BMC, and vBMD was growth
      related. CONCLUSIONS: Altering structural design while minimizing mass achieves
      FN strength and lightness. Bone fragility may be the result of failure to adapt
      bone's architecture to loading, not just low bone mass.

PMID- 17501647
TI  - Recall of pet food leaves veterinarians seeking solutions.

PMID- 17501648
TI  - Objects to analgesic procedures in cat study.

PMID- 17501649
TI  - What is your diagnosis? Severe subcutaneous emphysema.

PMID- 17501650
TI  - What is your diagnosis? Mineralization of the caudal horn of the medial meniscus.

PMID- 17501651
TI  - Outcomes assessment of an alternative career choice program.
AB  - OBJECTIVE: To assess the outcomes of an alternative track program designed to
      address shortages of veterinarians in nonpractice areas of the veterinary
      profession. DESIGN: Telephone survey. STUDY POPULATION: Recent veterinary
      graduates. PROCEDURES: A telephone survey of recent graduates from the Texas A&M
      University College of Veterinary Medicine and Biomedical Sciences Alternative
      Career Choice program was conducted. Respondents were asked to give open-ended
      responses to a list of 9 interview questions. RESULTS: Of the 21 alternative
      career choice students who graduated between the years 2000 and 2005, 17 were
      interviewed. CONCLUSION: Analysis of the data suggested that it may be possible
      to decrease the total number of weeks allotted to the alternate career choice
      program without impairing the ability of graduates to find employment in their
      chosen career fields.

PMID- 17501652
TI  - What veterinary practitioners should know about scrapie.
AB  - Scrapie is the longest known and most widely spread of the transmissible
      spongiform encephalopathies and remains the model for much of the research
      regarding these diseases. Because scrapie is a reportable disease and the subject
      of an active eradication program in the United States, veterinary practitioners
      should have a basic understanding of the disease.

PMID- 17501653
TI  - Association of microalbuminuria and the urine albumin-to-creatinine ratio with
      systemic disease in cats.
AB  - OBJECTIVE: To determine the diagnostic usefulness of semiquantitative and
      quantitative microalbuminuria assays and urine albumin-to-creatinine (UAC) ratio
      for detecting disease in cats. DESIGN: Prospective study. ANIMALS: 441 cats
      evaluated at a veterinary teaching hospital. PROCEDURES: Urine samples from cats
      for which a complete medical record was available were included. Urine dipstick
      results, urine protein-to-creatinine ratios (cutoffs, 0.1 and 0.4),
      semiquantitative and quantitative microalbuminuria assay results (cutoff, 1
      mg/dL), and UAC ratio values (cutoffs, 100 and 200 mg/g) were determined.
      Clinical diagnoses determined within 3 months of enrollment were recorded.
      Sensitivity and specificity were determined with disease status used as the
      standard. The influences of clinical diagnosis, sex, age, serum urea nitrogen and
      creatinine concentrations, blood pressure, bacterial urine culture results,
      rectal temperature, pyuria, hematuria, and bacteriuria were evaluated by means of
      logistic regression. RESULTS: Of 441 cats that were eligible for inclusion, 40
      were healthy and 401 had > or = 1 disease. Results of logistic regression
      indicated that significant associations existed for age, presence of disease,
      presence of urinary tract disease, azotemia, hematuria, and pyuria and results of
      1 or both of the microalbuminuria assays. CONCLUSIONS AND CLINICAL RELEVANCE:
      Microalbuminuria was associated with underlying disease. Sensitivity and
      specificity of the microalbuminuria assays for detection of systemic disease were
      superior to those of other tests. Microalbuminuria testing in conjunction with
      other screening procedures may increase identification of occult disease. A
      prospective study evaluating the predictive values of screening tests with and
      without microalbuminuria determination is needed to validate this recommendation.

PMID- 17501654
TI  - Use of chemical ablation with trichloroacetic acid to treat eyelid apocrine
      hidrocystomas in a cat.
AB  - CASE DESCRIPTION: A 7-year-old Persian cat was evaluated for recurrence of
      multiple cystic periocular masses. A number of cyst-like lesions had been
      resected from the left eyelids 18 months earlier, with lesions recurring within 6
      months after surgery. The cat had blepharospasm and signs of discomfort following
      rupture of the largest cyst the day prior to examination. Previous histologic
      examination of the cysts had revealed apocrine hidrocystomas. CLINICAL FINDINGS:
      Multiple pigmented nodules were seen around the skin of the upper and lower left
      eyelids. The nodules were brownish to black, round, soft, and fluid-filled. Signs
      of pain were not evident during palpation of the nodules. TREATMENT AND OUTCOME:
      The largest cyst on the upper eyelid was removed by means of a V-shaped full
      thickness excision. Histologic and immunohistochemical examination of the excised
      tissue confirmed the diagnosis of apocrine hidrocystoma. The remaining periocular
      cysts were surgically debrided and then treated topically with 20%
      trichloroacetic acid. All lesions healed rapidly without any signs of discomfort.
      During a recheck examination 12 months later, the upper and lower left eyelids
      appeared morphologically normal, and there was no evidence of recurrence.
      CLINICAL RELEVANCE: Findings suggested that chemical ablation with
      trichloroacetic acid may be a useful treatment for apocrine hidrocystomas in
      cats.

PMID- 17501656
TI  - Zinc intoxication in dogs: 19 cases (1991-2003).
AB  - OBJECTIVE: To determine physical examination findings, clinicopathologic changes,
      and prognosis in dogs with zinc toxicosis. DESIGN: Retrospective case series.
      ANIMALS: 19 dogs with zinc toxicosis. PROCEDURES: Medical records from 1991
      through 2003 were searched for animals with a diagnosis of zinc toxicosis.
      Information concerning signalment, body weight, historical findings, initial
      owner complaints, physical examination findings, clinicopathologic findings,
      blood zinc concentrations, source of zinc, treatments given, duration of hospital
      stay, and outcome was collected. RESULTS: Records of 19 dogs with zinc toxicosis
      were reviewed. The most common historical findings were vomiting (n = 14) and
      pigmenturia (12). The most common clinicopathologic findings were anemia (n = 19)
      and hyperbilirubinemia (12). Median age was 1.3 years, and median weight was 5.6
      kg (12.3 lb). The prognosis was favorable, with 17 dogs surviving after a median
      hospital stay of 2 days. CONCLUSIONS AND CLINICAL RELEVANCE: Hemolytic anemia as
      a result of zinc toxicosis appeared to affect young small-breed dogs more
      frequently than older large-breed dogs. The prognosis with treatment is good, and
      most affected dogs had a short hospital stay.

PMID- 17501657
TI  - Measurement of serum antinuclear antibody titer in dogs with and without systemic
      lupus erythematosus: 120 cases (1997-2005).
AB  - OBJECTIVE: To determine serum antinuclear antibody (ANA) titers in dogs with
      systemic lupus erythematosus (SLE) and in dogs with related clinical and
      clinicopathologic findings. DESIGN: Retrospective case series. ANIMALS: 120 dogs.
      PROCEDURES: Information that was evaluated included signalment, clinical signs,
      results of routine laboratory testing, ANA titer, and diagnosis. RESULTS: The
      most common clinical signs were arthralgia, myalgia, and stiffness (n = 41
      [34.2%]); the most common clinicopathologic abnormality was thrombocytopenia (30
      [25%]). Serum ANA titer was < 160 (seronegative) in 89 dogs (74.2%), 160 in 14
      dogs (11.7%), 320 in 5 dogs (4.2%), and > or = 640 in 12 dogs (10%). Immune
      mediated disease was confirmed in 40 dogs, 18 of which fulfilled the criteria for
      a definitive or probable diagnosis of SLE. Only 1 of 47 dogs with no major signs
      compatible with SLE had immune-mediated disease, compared with 26 of 57 dogs with
      1 major sign and 13 of 16 dogs with > or = 2 major signs. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that measurement of ANA titer was not a
      useful diagnostic test in dogs without any major clinical or clinicopathologic
      abnormalities suggestive of SLE. In contrast, there was a good chance that
      results of the ANA assay would be positive and that the dog would be found to
      have immune-mediated disease if at least 2 major signs were evident. Findings
      suggest that it would be reasonable to limit the use of the ANA assay to those
      dogs that have at least 1 major sign compatible with a diagnosis of SLE.

PMID- 17501659
TI  - Outcome of and complications associated with tube cystostomy in dogs and cats: 76
      cases (1995-2006).
AB  - OBJECTIVE: To determine indications for cystostomy tube use in dogs and cats,
      complications associated with their use, and outcome of dogs and cats in which
      cystostomy tubes had been inserted. DESIGN: Retrospective case series. ANIMALS:
      37 dogs and 39 cats. PROCEDURES: Information was obtained from medical records.
      Long-term follow-up information was obtained by use of a client questionnaire.
      RESULTS: Indications for cystostomy tube placement were bladder dysfunction,
      urinary tract rupture, obstructive urinary tract neoplasia, urinary diversion
      following urogenital surgery, obstructive urolithiasis, and feline lower urinary
      tract disease. Median time tubes were in place was 11 days, but duration of tube
      use was significantly longer for animals with bladder dysfunction than for
      animals with urinary tract trauma, urinary diversion, or urinary tract
      obstruction. Thirty-seven (49%) animals had tube complications. Development of
      complications was not significantly associated with species, age, body weight,
      duration of tube use, or tube type, except that animals were significantly more
      likely to develop complications following long-rather than short-term use. In 42
      animals, the underlying condition resolved and the tube was removed; 22 animals
      died or were euthanatized with the tube in place. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that cystostomy tubes may be used for animals with
      various conditions related to problems with urine outflow. Nearly half the
      animals in the study developed complications related to the cystostomy tube,
      suggesting that potential complications should be discussed with owners prior to
      tube placement. However, most complications were easily resolved.

PMID- 17501661
TI  - Comparison of classic hypoadrenocorticism with glucocorticoid-deficient
      hypoadrenocorticism in dogs: 46 cases (1985-2005).
AB  - OBJECTIVE: To compare dogs with glucocorticoid-deficient hypoadrenocorticism
      (GDH) with those with mineralocorticoid- and glucocorticoid-deficient
      hypoadrenocorticism (MGDH) and determine prevalence, historical and
      clinicopathologic markers, and outcome of dogs with GDH. DESIGN: Retrospective
      case series. ANIMALS: 46 dogs with hypoadrenocorticism. PROCEDURES: Records in
      the veterinary medical database at Purdue University were searched for dogs in
      which hypoadrenocorticism had been diagnosed at the Veterinary Teaching Hospital
      from 1985 to 2005. Data pertaining to signalment, history, a minimum
      clinicopathologic database, treatment, and outcome were collected. Dogs with
      hypoadrenocorticism were classified as having MGDH if hyponatremia, hyperkalemia,
      or both were detected and as having GDH if hyponatremia and hyperkalemia were
      absent. Dogs were excluded if they had ever been treated with mitotane or had
      been treated with > 1 dose of corticosteroids within a month prior to the ACTH
      stimulation test. RESULTS: 35 dogs with MGDH and 11 dogs with GDH met the
      inclusion criteria. Dogs with GDH were older at the time of diagnosis and had a
      longer duration of clinical signs prior to diagnosis than those with MGDH. Dogs
      with GDH were more likely to be anemic, hypoalbuminemic, and hypocholesterolemic
      than dogs with MGDH. CONCLUSIONS AND CLINICAL RELEVANCE: GDH was more common than
      reported in a referral hospital population of dogs with primary
      hypoadrenocorticism. Definitive diagnosis of GDH remains a clinical challenge.
      Absence of a stress leukogram in dogs with signs of illness (especially relating
      to the gastrointestinal tract) warrants further investigation. Most dogs with
      primary cortisol deficiency do not develop mineralocorticoid deficiency.

PMID- 17501662
TI  - Factors associated with outcome following treatment of horses with septic
      tenosynovitis: 51 cases (1986-2003).
AB  - OBJECTIVE: To identify factors associated with outcome (ie, survival and return
      to function) following treatment of horses with septic tenosynovitis. DESIGN:
      Retrospective case series. ANIMALS: 51 horses with septic tenosynovitis.
      PROCEDURES: Information was obtained from medical records and through follow-up
      conversations with owners. Factors analyzed for an association with outcome
      included affected limb, etiology, duration of clinical signs prior to
      examination, presence of complications, primary treatment, secondary treatments,
      number of surgical procedures, and hospitalization time. RESULTS: Concurrent
      complications were identified in 41 (80%) horses. The primary treatment consisted
      of through-and-through lavage in 26 (51%) horses, tenoscopy in 20 (39%), and
      tenosynoviotomy combined with lavage in 5 (10%). Forty (78%) horses were
      discharged, and 37 (73%) survived at least 1 year after surgery; 21 of the 37
      (57%) returned to their previous or a higher level of performance. Percentages of
      horses that survived 1 year after discharge and percentages that returned to
      their intended use did not vary significantly among treatments. Horses with
      tendon rupture or sepsis of an adjacent joint were significantly less likely to
      survive. Horses with tendon injury or pannus were significantly less likely to
      return to their intended use. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that various factors were associated with outcome in horses with septic
      tenosynovitis. However, surgical technique was not found to be associated with
      survival rate or rate of return to intended use.

PMID- 17501663
TI  - Internal fixation of a femur fracture in an American bullfrog.
AB  - CASE DESCRIPTION: An adult male American bullfrog (Rana catesbeiana) was
      evaluated by the North Carolina State University College of Veterinary Medicine's
      Turtle Rescue Team following vehicular trauma. CLINICAL FINDINGS: A fracture of
      the left femur was suspected on examination and palpation of the hind limbs, but
      no other injuries or abnormalities were detected. While the bullfrog was sedated,
      whole-body radiographic views were obtained, which revealed a closed midshaft
      comminuted fracture of the left femur. TREATMENT AND OUTCOME: The fracture was
      repaired by use of an internal fixation technique that included Kirschner wires,
      a positive-profile pin secured along the femur with encircling sutures, and
      polymethylmethacrylate molded around the entire apparatus. There were no major
      complications during the postoperative rehabilitation period. One year after
      surgery, radiography revealed complete fracture healing and the bullfrog was
      released back into the wild. CLINICAL RELEVANCE: Presently, there are no widely
      accepted methods for fracture fixation in amphibians. Factors associated with
      their aquatic environment and lengthy fracture healing time must be addressed
      when planning fracture fixation strategies. In the bullfrog of this report, the
      applied internal fixation method provided effective long-term stabilization of
      the femur, allowed for normal movement, and enabled the bullfrog to be housed in
      an aquatic environment immediately after surgery.

PMID- 17501665
TI  - Further insights in the mechanisms of interleukin-1beta stimulation of
      osteoprotegerin in osteoblast-like cells.
AB  - The mechanisms of IL-1beta stimulation of OPG were studied in more detail.
      Whereas p38 and ERK activation was confirmed to be needed, NF-kappaB was not
      necessary for this regulation. We also found that OPG production after IL-1beta
      stimulation was not sufficient to block TRAIL-induced apoptosis in MG-63 cells.
      INTRODUCTION: Osteoprotegerin (OPG) plays a key role in the regulation of bone
      resorption and is stimulated by interleukin (IL)-1beta. Herein, we defined the
      mechanisms of IL-1beta stimulation of OPG focusing on the potential involvement
      of MAPK and NF-kappaB. We also examined whether OPG production in response to IL
      1beta influences TRAIL-induced apoptosis in MG-63 cells. MATERIALS AND METHODS:
      OPG mRNA levels in MG-63 cells were quantified by real-time RT-PCR and protein
      levels of OPG and IL-6 by ELISA. Cell viability was assessed using the
      methyltetrazidium salt (MTS) reduction assay. The role of the MAPK pathway was
      studied by both Western blotting and the use of specific chemical inhibitors. NF
      kappaB function was studied using BAY 11-7085 and by siRNA transfection to
      inhibit p65 synthesis. Transcription mechanisms were analyzed by transiently
      transfecting MG-63 cells with OPG promoter constructs. Post-transcriptional
      effects were examined by using cycloheximide and actinomycin D. RESULTS: MG-63
      cells treatment with IL-1beta resulted in the phosphorylation of c-Jun NH(2)
      terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). The
      use of the specific inhibitors showed that p38 and ERK but not JNK were needed
      for IL-1beta-induced OPG production. In contrast, NF-kappaB was not essential for
      IL-1beta induction of OPG. We also showed a small transcriptional and a possible
      post-transcriptional or translational regulation of OPG by IL-1beta. Exogenous
      OPG blocked TRAIL-induced apoptosis, but IL-1beta induction of OPG did not
      influence TRAIL-induced cell death. CONCLUSIONS: IL-1beta stimulates OPG
      production by mechanisms dependent on p38 and ERK. In contrast, NF-kappaB was not
      essential for this regulation. Although the relevance of IL-1beta stimulation of
      OPG is still not fully understood, our data showed that IL-1beta stimulation of
      OPG does not modify TRAIL-induced cell death.

PMID- 17501666
TI  - Can BMD assessed by DXA at age 8 predict fracture risk in boys and girls during
      puberty?: an eight-year prospective study.
AB  - This study reports on the association between DXA at age 8 and subsequent
      fractures in both male and female children. Bone densitometry at the total body
      and spine (but not hip) is a strong predictor of fracture (especially upper limb)
      during puberty. INTRODUCTION: The aim of this study was to determine if
      prepubertal DXA can predict fracture risk during puberty. MATERIALS AND METHODS:
      We studied 183 children who were followed for 8 yr (1460 person-years). Bone
      densitometry was measured at the total body, hip, and spine by DXA and reported
      as BMC, BMD, and bone mineral apparent density (BMAD). Fractures were self
      reported at age 16 with X-ray confirmation, RESULTS: There were a total of 63
      fractures (43 upper limb). In unadjusted analysis, only total body BMD showed an
      inverse relationship with upper limb fracture risk (p = 0.03). However, after
      adjustment for height, weight, age (all at age 8), and sex, total body BMC
      (HR/SD, 2.47; 95% CI, 1.52-4.02), spine BMC (HR/SD, 1.97: 95% CI, 1.30-2.98),
      total body BMD (HR/SD, 1.67; 95% CI, 1.18-2.36), total body BMAD (HR/SD, 1.54;
      95% CI, 1.01-2.37), and spine BMD (HR/SD, 1.53; 95% CI, 1.10, 2.22) were all
      significantly associated with upper limb fracture risk. Similar, but weaker
      associations were present for total fractures. There was a trend for
      overweight/obesity to be associated with increased upper limb fracture risk (HR,
      1.53/category; p = 0.08). CONCLUSIONS: Measurement of bone mass by DXA is a good
      predictor of upper limb fracture risk during puberty. Although we did not measure
      true BMD, the constancy of fracture prediction after a single measure suggests
      bone strength remains relatively constant during puberty despite the large
      changes in bone size.

PMID- 17501667
TI  - Osteoporosis in patients with diabetes mellitus.
AB  - Demographic trends with longer life expectancy and a lifestyle characterized by
      low physical activity and high-energy food intake contribute to an increasing
      incidence of diabetes mellitus and osteoporosis. Diabetes mellitus is a risk
      factor for osteoporotic fractures. Patients with recent onset of type 1 diabetes
      mellitus may have impaired bone formation because of the absence of the anabolic
      effects of insulin and amylin, whereas in long-standing type 1 diabetes mellitus,
      vascular complications may account for low bone mass and increased fracture risk.
      Patients with type 2 diabetes mellitus display an increased fracture risk despite
      a higher BMD, which is mainly attributable to the increased risk of falling.
      Strategies to improve BMD and to prevent osteoporotic fractures in patients with
      type 1 diabetes mellitus may include optimal glycemic control and aggressive
      prevention and treatment of vascular complications. Patients with type 2 diabetes
      mellitus may additionally benefit from early visual assessment, regular exercise
      to improve muscle strength and balance, and specific measures for preventing
      falls.

PMID- 17501668
TI  - Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the
      relationship to functional outcome.
AB  - Most lesions in FD and their attendant functional disability occur within the
      first decade; 90% of lesions are present by 15 years, and the median age when
      assistive devices are needed is 7 years. These findings have implications for
      prognosis and determining the timing and type of therapy. INTRODUCTION: Fibrous
      dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is
      replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal
      involvement and disability occur. The age at which lesions are established, the
      pace at which the disease progresses, if (or when) the disease plateaus, and how
      these parameters relate to the onset of disability are unknown. To answer these
      questions, we performed a retrospective analysis of a group of subjects with FD.
      MATERIALS AND METHODS: One hundred nine subjects with a spectrum of FD were
      studied for up to 32 years. Disease progression was assessed in serial (99)Tc-MDP
      bone scans by determining the location and extent of FD lesions using a validated
      bone scan scoring tool. Physical function and the need for ambulatory aids were
      assessed. RESULTS: Ninety percent of the total body disease skeletal burden was
      established by age 15. Disease was established in a region-specific pattern; in
      the craniofacial region, 90% of the lesions were present by 3.4 yr, in the
      extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were
      present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory
      aids. The median age at which assistance was needed was 7 yr (range, 1-43 yr).
      The median bone scan score for subjects needing assistance was 64.3 (range, 18.6
      75) compared with 23.1 (range, 0.5-63.5) in the unassisted subjects (p < 0.0001).
      Among subjects needing assistance with ambulation, 92% showed this need by 17 yr.
      CONCLUSIONS: The majority of skeletal lesions and the associated functional
      disability occur within the first decade of life. The implication is that the
      window of time for preventative therapies is narrow. Likewise, therapeutic
      interventions must be tailored to where the patient is in the natural history of
      the disease (i.e., progressive disease [young] versus established disease [older
      subjects]). These findings have implications for prognosis, the timing and type
      of therapy, and the development of trials of new therapies and their
      interpretation.

PMID- 17501688
TI  - 5-HT and the brain-gut axis: opportunities for pharmacologic intervention.
AB  - Interactions between the enteric nervous system of the gut and the brain occur
      bidirectionally over sympathetic and parasympathetic pathways. Coordinated
      actions of the central, autonomic and enteric nervous systems modulate intestinal
      motor, sensory and secretory activities by neuromodulators, including 5-HT,
      noradrenaline and dopamine. 5-HT is an important signaling molecule in the brain
      gut axis and the 5-HT released from enterochromaffin cells modulates peristaltic,
      secretory, vasodilatory, vagal and nociceptive reflexes. Irritable bowel syndrome
      is associated with altered motility, secretion and sensation; enteric 5-HT
      signaling may be defective in this disorder. In this editorial, recent data are
      reviewed and the potential for the development of pharmacologic intervention is
      assessed.

PMID- 17501689
TI  - New therapy for the prevention and prophylactic treatment of acute radiation
      syndrome.
AB  - The risk of military personnel, first responders and civilians being exposed to
      lethal doses of ionising radiation is greater now than it was during the Cold
      War. Due to the increasing likelihood of exposure to ionising radiation, the need
      for medical radiation countermeasures has been recognised as a high priority in
      the US. At present, no approved drugs are available for the prevention or
      treatment of acute radiation syndrome, even though this is a top national
      priority. One promising investigational drug candidate for the indication of
      radioprotection is BIO 300. This agent is a medical radiation countermeasure that
      is intended for use as a prophylactic treatment for acute radiation syndrome.
      Novel products (such as BIO 300) that provide prophylactic protection are
      designed to be shelf stable for several years, more rapidly distributed and
      easily administered orally with a minimum of medical supervision.

PMID- 17501690
TI  - Aripiprazole acts as a selective dopamine D2 receptor partial agonist.
AB  - Aripiprazole has made a significant contribution to the treatment of
      schizophrenia and related disorders with an improved safety and tolerability
      profile, which has been attributed to its unique pharmacological profile. It has
      been claimed that partial agonism of the dopamine D(2) and 5-HT(1A) receptors and
      antagonism of the 5-HT(2) receptor contribute to the clinical profile of
      aripiprazole, a so-called dopamine- and 5-HT stabiliser. However, recent studies
      have questioned the role of the 5-HT-mediated systems in the mechanism of action
      of aripiprazole. This report reviews published and unpublished data that suggest
      that aripiprazole acts as a selective partial agonist at the dopamine D(2)
      receptor and does not affect 5-HT receptors at therapeutic doses.

PMID- 17501691
TI  - Treatment paradigms on hepatitis B e antigen-negative chronic hepatitis B
      patients.
AB  - The primary goal of treatment in hepatitis B e antigen (HBeAg)-negative patients
      with chronic hepatitis B (CHB) is potent and durable suppression of hepatitis B
      virus (HBV) replication. It results in biochemical and histological remission of
      CHB and is the prerequisite for the prevention of cirrhosis, its life-threatening
      complications and hepatocellular carcinoma. Responses that are durable after the
      cessation of treatment are referred to as sustained virological responses,
      whereas those persisting under therapy are referred to as treatment-maintained
      virological responses. Treatment paradigms of sustained virological response in
      HBeAg-negative CHB are practically restricted to conventional IFN-alpha and
      pegylated interferons (peg-IFNs), and are limited only to patients with
      compensated liver disease. Long-lasting maintained virological responses without
      HBV resistance in HBeAg-negative CHB are achievable by all approved nucleos(t)ide
      analogues (lamivudine, adefovir and entecavir) in highly variable rates,
      depending on their potency, rapidity of virological response and genetic barrier
      to resistance. The maintenance of response under 5 years of adefovir treatment
      represents the most effective treatment paradigm for HBeAg-negative CHB, whereas
      such long-term data with entecavir and tenofovir monotherapy may become available
      in the near future. In patients with lamivudine-resistant HBV mutants, the
      recommended treatment strategy is to add adefovir at the same time as continuing
      treatment with lamivudine. There are no treatment paradigms as yet of combination
      therapy from the very outset with two nucleoside analogues for use in treatment
      naive patients.

PMID- 17501692
TI  - Immunomodulation as an option for the treatment of chronic hepatitis B virus
      infection: preclinical studies in the woodchuck model.
AB  - New therapeutic approaches for chronic hepatitis B virus infection based on
      immunomodulation are now under investigation. The woodchuck model for hepatitis B
      virus infection has emerged as a useful animal model for the evaluation of such
      approaches, after developing necessary assays and reagents for immunologic
      studies in this model. Conventional and novel vaccines such as DNA vaccines were
      tested in woodchucks for their ability to induce protective immune responses
      against challenge infection with the woodchuck hepatitis virus (WHV).
      Furthermore, immunotherapeutic approaches for the control of chronic hepadnaviral
      infection were evaluated in woodchucks. Immunizations with WHV proteins and DNA
      vaccines led to the development of antibodies to the WHV surface antigen and to a
      significant decrease of viral load in chronically WHV-infected woodchucks. Viral
      vector-mediated gene transfer was explored for the delivery of antiviral
      cytokines IFN-alpha in woodchucks and resulted in the decrease of viral
      replication. It is now generally accepted that a combination of antiviral
      treatment and immunization will be necessary to achieve successful
      immunomodulation with a long-term control of chronic hepatitis B virus infection.

PMID- 17501693
TI  - Emerging therapies for pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension is characterised by increased pulmonary vascular
      resistance due to increased vascular tone and structural remodelling of pulmonary
      vessels. The therapies that are in use so far have been developed to correct
      endothelial dysfunction and reduce vasomotor tone. These treatments have a
      limited effect on the remodelling process and, increasingly, the focus is turning
      to potent strategies for inhibiting vascular proliferation and promoting vascular
      apoptosis. Multiple novel targets have been uncovered over the last 5 years and
      several are now in early clinical trials. At present, it is clear that there is
      no single treatment for the condition. Although this is the case, studies are
      investigating the role of combining therapies that are already established.

PMID- 17501694
TI  - Clinical immunologic approaches for the treatment of Alzheimer's disease.
AB  - Recent clinical trials of active vaccination against beta-amyloid (Abeta) have
      succeeded in clearing Abeta plaques; however, further understanding of
      immunization with regards to inflammation and other hallmarks of Alzheimer's
      disease pathology is required. Antibodies generated with this first-generation
      vaccine may not have had the desired therapeutic properties or targeted the
      'correct' mechanism, but they have opened the way for new clinical approaches,
      which are now under consideration. Passive administration of monoclonal
      antibodies directed to various regions of Abeta peptide and/or administration of
      immunoconjugates of only small fragments of the N-terminal region may lead to the
      development of an improved second generation of Abeta vaccines. Amyloid
      immunotherapy offers genuine opportunities for disease treatment; however, such
      an approach towards treating and preventing Alzheimer's disease patients requires
      careful antigen and antibody selection to maximize efficacy and minimize adverse
      events.

PMID- 17501695
TI  - Novel pharmacotherapy for fibromyalgia.
AB  - Fibromyalgia is a common disorder that is characterized by chronic widespread
      pain, tenderness to light palpation, fatigue and sleep disturbances. The present
      lack of a well-accepted model of the disorder has hampered progress towards
      adequate treatment. A review of potential models to explain the pathophysiology
      underlying its primary symptom (i.e., chronic widespread pain) lends insight on
      the therapeutic potential of novel therapies. Following this, a mechanistic
      evaluation of those medications that are under consideration for the treatment of
      the disorder is offered. Adequate treatment will be likely to involve the
      identification of biologic subgroups within the greater fibromyalgia construct.
      Key insights from basic research are the basis for increased optimism for
      effective relief among patients and clinicians.

PMID- 17501696
TI  - The choice of a tocolytic for the treatment of preterm labor: a critical
      evaluation of nifedipine versus atosiban.
AB  - Preterm birth is the major cause of neonatal mortality and morbidity in the
      developed world. The perfect tocolytic that is uniformly effective with complete
      fetomaternal safety does not exist. Tocolytic agents differ in cost, utero
      specificity, safety, efficacy and whether they are licensed for use. The main
      three agents that are used worldwide are beta-agonists, Ca(2+) channel blockers
      and vasopressin/oxytocin receptor antagonists. beta-Agonists are gradually being
      phased out of use and are being replaced by either nifedipine or atosiban. The
      evidence base for atosiban is strong but the evidence is of poor quality for
      nifedipine. The balance of evidence indicates that atosiban is as effective as
      nifedipine and more effective than beta-agonists and is significantly safer than
      both. Atosiban was developed specifically to treat preterm labor, so the cost is
      higher than nifedipine or ritodrine. However, the cost of a course of atosiban
      (approximately 200 pounds) should not only be considered in comparison with other
      tocolytic agents but to other medical budgets (e.g., oncology, fertility,
      cardiology and psychiatry) and to the huge healthcare costs associated with the
      morbidity and mortality caused by preterm birth. Atosiban is a new advance in the
      management of spontaneous preterm labor.

PMID- 17501697
TI  - DOXO-EMCH (INNO-206): the first albumin-binding prodrug of doxorubicin to enter
      clinical trials.
AB  - The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) is an
      albumin-binding prodrug of doxorubicin with acid-sensitive properties that
      demonstrates superior antitumor efficacy in murine tumor models and a favorable
      toxicity profile in mice, rats and dogs, including significantly reduced
      cardiotoxicity. After intravenous administration, DOXO-EMCH binds rapidly to the
      Cys-34 position of circulating albumin and accumulates in solid tumors due to
      passive targeting. In a clinical Phase I study, the dose of doxorubicin could be
      increased by a factor of 4.5-340 mg/m(2) when 75 mg/m(2) of free doxorubicin is
      considered to be the dose that can be administered as a single agent concomitant
      with the typical spectrum of side effects (i.e., myelotoxicity and mucositis).
      DOXO-EMCH was able to induce tumor regressions in anthracycline-sensitive tumors
      (i.e., breast cancer, small cell lung cancer and sarcoma). Phase II studies will
      be initiated at the beginning of 2007.

PMID- 17501698
TI  - Emerging therapies for colorectal cancer.
AB  - Colorectal carcinoma is a leading cause of cancer mortality worldwide. Survival
      for patients with metastatic disease is approximately 2 years on average and
      there is an ongoing need for the identification of new therapeutic agents. As the
      cancer research community has appreciated, newly discovered pathways governing
      cancer cell growth, survival, apoptosis, invasion and angiogenesis--all a host of
      potential therapeutic targets--have come into view. Basic research, preclinical
      data and observations arising from early stage trials have pointed towards
      possible roles for many of these agents in the future treatment of colorectal
      cancer. In this review, the authors summarize agents in development, modulating
      several of the most promising molecules and pathways that are thought to be
      relevant to colorectal cancer.

PMID- 17501699
TI  - Biocatalytic and semisynthetic studies of the anticancer tobacco cembranoids.
AB  - Historically, tobacco use was primarily recreational and has been smoked in
      cigarettes, cigars and pipes, as well as smokeless forms of consumption, all of
      which are associated with adverse health effects. However, recent scientific
      investigations indicate that tobacco also contains several diverse secondary
      metabolites that may provide potential health benefits in the treatment of cancer
      and neurodegenerative diseases. Specifically, the leaf and flower of Nicotiana
      tabacum contain high amounts of the key flavor ingredient, cembranoids. Tobacco
      alpha- and beta-2,7,11-cembratriene-4,6-diols display potent anticancer activity.
      These compounds have also been found to inhibit phorbol ester-stimulated (32)P(i)
      incorporation into phospholipids, induction of Epstein-Barr virus early antigen
      and protein phosphorylation. This review focuses on the biocatalytic and
      semisynthetic studies of tobacco cembanoids and their anticancer activity.

PMID- 17501700
TI  - Novel medications for asthma: a look at the future.
AB  - The principal components of the asthmatic response are airways hyper
      responsiveness, persistent inflammation and mucus hypersecretion. Although these
      components are inter-related, any of these can predominate at different times and
      for different patients and each requires a different approach to therapy. As a
      result of the inflammation and epithelial damage, there can be abnormal repair
      mechanisms leading to fixed airflow obstruction that has been termed 'airways
      remodeling'. Although there are a number of highly effective therapeutic agents
      used to treat asthma today, novel therapies are being designed to more
      specifically and safely target these different components and better meet the
      needs of patients with asthma.

PMID- 17501701
TI  - The use of caspofungin in HIV-infected individuals.
AB  - Fungal infections are a significant cause of HIV-related morbidity and mortality,
      particularly in the developing world, but also in countries with access to highly
      active antiretroviral therapy. New agents are essential to improve present
      efficacy rates, particularly in cases of drug resistance. Caspofungin is a new
      antifungal from the echinocandin class and is licensed for the treatment of
      candidal infections and as a second-line therapy for invasive aspergillosis. In
      this paper, the pharmacology, interaction and susceptibility data for this agent
      are reviewed and studies supporting the use of this agent in HIV-infected
      individuals are examined. Finally, evidence for the use of caspofungin for the
      treatment of Pneumocystis jiroveci pneumonia, an unlicensed indication, including
      a case series from our own unit is explored.

PMID- 17501702
TI  - 11th annual Inflammatory and Immune Diseases Drug Discovery and Development
      Summit 12-13 March 2007, San Francisco, USA.
AB  - The Strategic Research Institute (SRi) hosted the 11th International Inflammation
      and Immune Diseases Drug Discovery and Development World Summit in San Francisco
      during 12-13 March 2007. The summit comprised keynote sessions and two parallel
      tracks and focussed on targeting mechanisms for drug discovery and development,
      which modulate the immune response and which have anti-inflammatory activity in a
      number of human diseases. Indications included psoriasis, hepatitis C, allergic
      dermatitis, systemic lupus erythematosus, rheumatoid arthritis and
      osteoarthritis, multiple sclnerosis, cardiovascular disease and asthma. Data were
      presented supporting all stages of drug discovery from target identification and
      validation through to lead identification and optimisation to both early- and
      late-stage clinical development.

PMID- 17501703
TI  - Values and principles evident in current health promotion practice.
AB  - ISSUE ADDRESSED: Modern health promotion practice needs to respond to complex
      health issues that have multiple interrelated determinants. This requires an
      understanding of the values and principles of health promotion. METHOD: A
      literature review was undertaken to explore the values and principles evident in
      current health promotion theory and practice. RESULTS: A broad range of values
      and principles are espoused as being integral to modern health promotion theory
      and practice. Although there are some commonalities across these lists, there is
      no recognised, authoritative set of values and principles accepted as fundamental
      and applicable to modern health promotion. There is a continuum of values and
      principles evident in health promotion practice from those associated with
      holistic, ecological, salutogenic health promotion to those more in keeping with
      conventional health promotion. CONCLUSION: There is a need for a system of values
      and principles consistent with modern health promotion that enables practitioners
      to purposefully integrate these values and principles into their understanding of
      health, as well as their needs assessment, planning, implementation and
      evaluation practice.

PMID- 17501705
TI  - A perspective on changes in values in the profession of health promotion.

PMID- 17501706
TI  - The Red Lotus Health Promotion Model: a new model for holistic, ecological,
      salutogenic health promotion practice.
AB  - ISSUE ADDRESSED: There is a need for a system of values and principles consistent
      with modern health promotion that enables practitioners to use these values and
      principles to understand health and in their needs assessment, planning,
      implementation and evaluation practice. METHOD: Grounded theory, document
      analysis and the authors' own practice experience were used to systematically
      collect and analyse data from key health promotion literature and to develop the
      Red Lotus Health Promotion Model. RESULTS: The Red Lotus Health Promotion Model
      is a new model for holistic, ecological, salutogenic health promotion practice.
      It is distinct from other health promotion models in that it incorporates a
      system of values and principles that is applied across the phases of health
      promotion, including determining the health paradigm, needs assessment, planning,
      implementation and evaluation. CONCLUSION: The Red Lotus Health Promotion Model
      enables practitioners to proactively and purposefully put into action a connected
      system of values and principles across the phases of a health promotion process.

PMID- 17501707
TI  - Beyond masculine stereotypes: moving men's health promotion forward in Australia.
AB  - There has been increased interest in men's health over the past two decades. A
      major focus has been on men's apparent reluctance to seek health-related help. As
      such, innovative methods to facilitate health promotion engagement and preventive
      health practices among men have emerged. Men's health promotion activity in
      Australia has paid particular attention to settings and social marketing
      approaches. These, more often than not, have been aligned to hegemonic
      constructions of masculinity. As such, traditional gender-roles are perpetuated,
      which may, despite best intentions, reinforce negative health behaviours among
      men. However, the health promotion community is well positioned to strategically
      free men from the constraints of hegemonic masculinity. By paying attention to
      commentary relating to the social construction of gender, an alternative pathway
      is evident. Of particular interest is discussion relating to multiple
      masculinities, in contrast to one dominant form. This opens the door to develop a
      range of health promotion interventions targeted to specific groups of men,
      including those that are most marginalised and disadvantaged. In doing so, health
      inequities among men relating to age, class, sexuality, race and ethnicity can be
      more purposefully addressed. This paper explores the intersection between current
      health promotion practice and recent commentary relating to gender. I conclude by
      suggesting that health promotion researchers, practitioners and policy makers
      need to account for multiple masculinities in the planning, development,
      implementation and evaluation of health promotion activities aimed at men in
      order to move men's health promotion forward in Australia.

PMID- 17501708
TI  - Phased in smoke-free workplace laws: impact in grass-roots pubs and clubs in
      South Australia.
AB  - ISSUE ADDRESSED: Smoke-free workplace laws with phase-in provisions for licensed
      bar and gaming venues are being rolled-out across Australia. This study
      investigates grass-roots industry reactions after the first phase of
      implementation in South Australia and compares them with views of patrons who
      smoke. METHODS: Two surveys were conducted with bar and club managers of randomly
      selected licensed venues in South Australia. The first survey (baseline) was
      conducted in November 2004 (n=500; by telephone). The second survey (phase 1) was
      conducted in May 2005 (n=357; in person including site inspection). Community
      support was assessed in a telephone survey conducted in 2005 (n=2,004). RESULTS:
      In 2005, more than half supported the smoking bans planned for 2007 and up to 75%
      supported the phase-in provisions (for 2005-07). By 2005, 90.7% recognised it was
      important to provide a smoke-free environment for staff, but one-third were under
      the mistaken impression that phase-in measures offered health protection.
      Attempted compliance was very high and, for most, not an effort or financial
      burden. Verified compliance was fair, although lower than self-report due to
      confusion about rules for smoking and non-smoking areas. When the views of bar
      and club managers were compared with community views, collected in a separate
      survey, it was found that bar and club managers substantially under-estimated
      community support for impending total smoke-free laws, due in November 2007.
      CONCLUSIONS: Grass-roots industry support for smoke-free laws is considerable and
      higher than industry comments might imply, but somewhat lesser than community
      support. Attempted compliance is fair, despite confusion about details.

PMID- 17501709
TI  - Effects of a walking program in the psychiatric in-patient treatment setting: a
      cohort study.
AB  - ISSUE ADDRESSED: To assess the effectiveness of a walking program in a
      psychiatric in-patient unit. METHOD: In-patients at a private psychiatric unit
      were offered the opportunity to participate in a daily morning 40- minute walk
      led by an activity supervisor. After discharge, outcomes for patients who had
      regularly participated in the walking group (n=35) and patients who had not
      participated (n=49) were compared for length of stay during their period of
      admission and Clinical Global Impression-Severity (CGI-S) and Depression Anxiety
      Stress Scales (DASS) scores measured at admission and discharge. This was a
      retrospective analysis of data collected routinely. RESULTS: There were no
      significant differences between the two cohorts on most primary outcome measures,
      including length of stay, DASS scores at admission and at discharge and CGI-S
      scores at admission. Patients who had not participated in the walking group had a
      significantly lower score on a single measure, the CGI-S, than patients who had
      participated (p=0.001). CONCLUSIONS: This study showed no evidence that in
      patients benefited from participating in the physical activity program. However,
      this must be interpreted within the confines of a number of study limitations
      and, as such, the findings can neither support nor refute the effectiveness of
      physical activities.

PMID- 17501710
TI  - An evaluability assessment of a nutrition promotion project for newly arrived
      refugees.
AB  - ISSUE ADDRESSED: This paper reports on the benefits of conducting an evaluability
      assessment for a nutrition promotion project for newly arrived refugees to Perth,
      Western Australia. The assessment was the first step in a planned outcome
      evaluation. It was undertaken to contribute to the body of knowledge regarding
      nutritional health and promotion for newly arrived refugees to Australia.
      METHODS: Using semi-structured interviews with stakeholders, observation,
      presentations of early drafts of the program logic to key stakeholders and a
      review of the documentation, the analysis of qualitative data was used to make
      the project logic explicit and to better understand the project's underlying
      cause and effect relationships. RESULTS: The analysis alongside a review of
      contemporary health promotion literature revealed that the original underlying
      project logic needed refinement. A more complex and relevant project logic was
      developed which confirmed that the project had the potential to achieve its goals
      of improving the nutritional status of refugees. CONCLUSIONS: The evaluability
      assessment gave stakeholders the opportunity to reflect on the project and its
      implementation issues. Importantly, it made more explicit the complexity of the
      context of the project and the need for a diverse range of strategies to improve
      nutrition. Finally, the diagrammatic representation of the reconstructed project
      logic provided a powerful advocacy tool for a multi-sectoral approach.

PMID- 17501711
TI  - People's beliefs about factors contributing to mental health: implications for
      mental health promotion.
AB  - ISSUE ADDRESSED: To quantify people's perceptions of mental health identified in
      qualitative research and to inform mental health promotion communication
      strategies. METHODS: A statewide telephone survey of 1,500 adults was conducted
      in Western Australia using a structured questionnaire containing both open and
      closed-ended questions. RESULTS: The vast majority of people had negative (or
      illness) connotations to the words 'mental health', but had positive connotations
      to the term 'mentally healthy person'. The three factors perceived to contribute
      most to being mentally healthy were: having good friends to talk problems over
      with; keeping one's mind active; and the opportunity to have control over one's
      life. The three factors perceived to contribute most to being mentally unhealthy
      were: excessive use of alcohol or drugs; having no friends or support network;
      and life crises o traumas. The phrase 'being content with who you are' best
      summed up good mental health. Older people generally placed greater emphasis than
      younger people on cognitive functioning and keeping physically healthy for good
      mental health. CONCLUSIONS: People's beliefs about factors influencing mental
      health are consistent with much of the literature. Communication components of
      mental health promotion interventions based on the data reported here would be
      viewed as credible and relevant by most people.

PMID- 17501712
TI  - Health priorities and perceived health determinants among South Australians
      attending GLBTI festival events.
AB  - ISSUE ADDRESSED: Health differentials related to the social position of people
      whose sexual attraction or gender identity differs from that of the majority may
      be the 'forgotten inequity' in contemporary Australian discourses on health
      inequalities and social inclusion. What sexually- and gender-diverse communities
      see as health priorities and the social determinants of their health have been
      little studied in Australia. This survey explored the experience and opinions of
      a convenience sample of gay, lesbian, bisexual, trangender and intersex (GLBTI)
      people in South Australia. METHOD: A pencil and paper survey was administered to
      people attending events associated with the Feast GLBTI festival in Adelaide in
      2004 and good participation rates were obtained. Two hundred and fifty-three
      people completed the survey, of which 122 identified as female, 124 as male and
      seven as other genders. RESULTS: Depression, HIV, suicide, family relationship
      problems and alcohol problems were seen as the most important health issues for
      these communities, while discrimination under the law and in daily life were
      rated the most important health determinants. CONCLUSIONS: GLBTI South
      Australians surveyed identified priority health issues for their communities and
      identified legal and personal discrimination as significant determinants of their
      health.

PMID- 17501713
TI  - Stress, culture and 'home': social context in Turkish and Arabic-speaking
      Australians' views of diabetes prevention.
AB  - ISSUE ADDRESSED: A high prevalence of type 2 diabetes and diabetes risk factors
      exists among Middle East-born communities, largely attributed to modifiable
      lifestyle factors. Understanding the interplay between individual behaviour and
      societal and environmental factors would assist in planning interventions to
      reduce diabetes prevalence in these groups. This study explores the knowledge,
      attitudes and perceptions of diabetes and its prevention in Turkish and Arabic
      speaking communities in metropolitan Melbourne, Victoria, Australia. METHOD:
      Turkish and Arabic-speaking people with risk factors of developing diabetes were
      invited to attend focus groups. Discussions were audiotaped and transcribed with
      the assistance of interpreters and then analysed by two researchers independently
      to ensure validity. Common themes were drawn upon and reported. RESULTS: Fifty
      two people (41 females and 11 males, mean age=58.8 years) participated in five
      focus groups. Understanding of diabetes and potential for reducing risk of
      diabetes is closely linked to social context. Individual behaviours around diet
      and exercise, while partly influenced by cultural factors, are framed by concerns
      about public safety and food quality, which are themselves closely linked to
      experiences of social exclusion and marginalisation. CONCLUSION: These factors
      limit potential for individual behaviour change and are implicated in the way
      chronic stress acts as a common pathway through which individual health comes to
      embody social context.

PMID- 17501714
TI  - Ethics in health promotion--reflections in practice.
AB  - Health promotion practitioners should be able to identify ethical dilemmas that
      are relevant to their practice and understand how to preclude and/or address such
      problems. This paper explores some of the broad ethical issues in health
      promotion practice; summarises some of the principles that require consideration;
      and outlines some of the recently developed ethical frameworks for public health
      and health promotion practice. Health promoters are encouraged to reflect not
      only on the consequences of their actions, but also their philosophical and
      ethical foundations.

PMID- 17501715
TI  - Maori physical activity: a review of an indigenous population's participation.
AB  - ISSUE ADDRESSED: Indigenous populations have disparities in health along with
      disparities in modifiable risk factors, including low participation in physical
      activity. Given the importance of physical activity in moderating ill health, do
      all indigenous peoples exhibit low activity prevalence in concert with ill
      health? If an indigenous population is relatively active, what can be learned
      about physical activity development that has underlined this activity and could
      this be transferred to practice in other countries? METHODS: A review of national
      surveys undertaken since 1997 reporting physical activity prevalence of New
      Zealanders of different ethnicities, including Maori, was conducted. This was
      compared with prevalence data from other countries gained from searches of
      databases including PubMed, MEDLINE, Sports Discus and government websites. Socio
      economic and environmental influences were examined with a view to understanding
      Maori physical activity prevalence. RESULTS: The proportion of active adult
      Maoris, the indigenous population of New Zealand, is similar to European New
      Zealanders. For example, the Ministry of Health has reported that 60% and 51% of
      Maori males and females respectively, and 58% and 50% of European men and women
      respectively, undertake at least 30 minutes of physical activity on at least five
      days per week. These findings are at odds with other indigenous populations, with
      the possible exception of Canada. The prevalence of undertaking no leisure-time
      physical activity is 48.7% for American Indian/Alaskan Native American women
      compared with 30.7% of white American women; 37.2% for American Indian/Alaskan
      Native American older adults compared with 29.3% of white American older adults;
      and 12% for Maori compared with 10% for all New Zealanders. CONCLUSIONS: Despite
      health disparities, Maori are at least as active as European New Zealanders. The
      reasons for this lack of disparity in physical activity prevalence between Maori
      and European New Zealanders could be due to environmental influences, including
      those in the socio-cultural and policy environment.

PMID- 17501716
TI  - Creating active playgrounds in primary schools.
AB  - ISSUE ADDRESSED: To identify a model for a process that will support schools to
      implement environmental modifications in playgrounds aimed at increasing physical
      activity. METHODS: Kidsafe NSW (Playground Advisory Unit) was commissioned by the
      former Illawarra Health Promotion Unit (IHPU) to develop playground concept
      designs, safety audits and detailed reports for three primary schools. Each
      report contained several environmental recommendations to increase participation
      in physical activity. During this study one school was destroyed by fire. The
      former IHPU supported the remaining two schools to implement environmental
      modifications for increasing physical activity through a process of meetings and
      interviews. RESULTS: Principals of both schools said they found the process to be
      valuable and it encouraged them to implement changes to their school environment
      for the purpose of increasing physical activity. School staff and the Parents and
      Friends Association felt that having a report from Kidsafe NSW increased the
      credibility and importance of the recommendations. Both schools made several
      changes to their playgrounds that were recommended in the report. CONCLUSIONS:
      The process of providing a Kidsafe NSW playground report, as well as support
      through meetings and interviews, appears to promote environmental change in
      schools.

PMID- 17501718
TI  - Effect of parathyroid-hormone-related protein on human platelet activation.
AB  - Evidence suggests that PTHrP [PTH (parathyroid hormone)-related protein] can act
      as an inflammatory mediator in several pathological settings including
      cardiovascular disease. The aim of the present study was to determine whether
      PTHrP might be involved in human platelet activation. We used a turbidimetric
      method to determine platelet aggregation. The expression of PTH1R (PTH type 1
      receptor) in human platelets was analysed by Western blot and flow cytometry
      analyses. PTHrP-(1-36) (10(-7) mol/l) by itself failed to modify the activation
      of platelets. However, it significantly enhanced ADP-induced platelet activation,
      and also increased the ability of other agonists (thrombin, collagen and
      arachidonic acid) to induce platelet aggregation. H89 (10(-6) mol/l) and 25 x 10(
      6) mol/l Rp-cAMPS (adenosine 3',5'-cyclic monophosphorothioate Rp-isomer), two
      protein kinase A inhibitors, and 25 x 10(-9) mol/l bisindolylmaleimide I, a
      protein kinase C inhibitor, partially decreased the enhancing effect of PTHrP-(1
      36) on ADP-induced platelet activation. Meanwhile, 10(-6) mol/l PTHrP-(7-34), a
      PTH1R antagonist, as well as 10(-5) mol/l PD098059, a MAPK (mitogen-activated
      protein kinase) inhibitor, or a farnesyltransferase inhibitor abolished this
      effect of PTHrP-(1-36). Moreover, 10(-7) mol/l PTHrP-(1-36) increased (2-fold
      over control) MAPK activation in human platelets. PTH1R was detected in
      platelets, and the number of platelets expressing it on their surface in patients
      during AMI (acute myocardial infarction) was not different from that in a group
      of patients with similar cardiovascular risk factors without AMI. Western blot
      analysis showed that total PTH1R protein levels were markedly higher in platelets
      from control than those from AMI patients. PTH1R was found in plasma, where its
      levels were increased in AMI patients compared with controls. In conclusion,
      human platelets express the PTH1R. PTHrP can interact with this receptor to
      enhance human platelet activation induced by several agonists through a MAPK
      dependent mechanism.

PMID- 17501719
TI  - Mechanism of interaction of optimized Limulus-derived cyclic peptides with
      endotoxins: thermodynamic, biophysical and microbiological analysis.
AB  - On the basis of formerly investigated peptides corresponding to the endotoxin
      binding domain from LALF [Limulus anti-LPS (lipopolysaccharide) factor], a
      protein from Limulus polyphemus, we have designed and synthesized peptides of
      different lengths with the aim of obtaining potential therapeutic agents against
      septic shock syndrome. For an understanding of the mechanisms of action, we
      performed a detailed physicochemical and biophysical analysis of the interaction
      of rough mutant LPS with these peptides by applying FTIR (Fourier-transform
      infrared) spectroscopy, SAXS (small-angle X-ray scattering), calorimetric
      techniques [DSC (differential scanning calorimetry) and ITC (isothermal titration
      calorimetry)] and FFTEM (freeze-fracture transmission electron microscopy). Also,
      the action of the peptides on bacteria of different origin in microbial assays
      was investigated. Using FTIR and DSC, our results indicated a strong fluidization
      of the lipid A acyl chains due to peptide binding, with a decrease in the
      endothermic melting enthalpy change of the acyl chains down to a complete
      disappearance in the 1:0.5 to 1:2 [LPS]:[peptide] molar ratio range. Via ITC, it
      was deduced that the binding is a clearly exothermic process which becomes
      saturated at a 1:0.5 to 1:2 [LPS]:[peptide] molar ratio range. The results
      obtained with SAXS indicated a drastic change of the aggregate structures of LPS
      into a multilamellar stack, which was visualized in electron micrographs as
      hundreds of lamellar layers. This can be directly correlated with the inhibition
      of the LPS-induced production of tumour necrosis factor alpha in human
      mononuclear cells, but not with the action of the peptides on bacteria.

PMID- 17501720
TI  - Global longitudinal strain measured by two-dimensional speckle tracking
      echocardiography is closely related to myocardial infarct size in chronic
      ischaemic heart disease.
AB  - 2D-STE (two-dimensional speckle tracking echocardiography) is a novel
      echocardiographic modality that enables angle-independent assessment of
      myocardial deformation indices. In the present study, we tested whether peak
      systolic epsilon(parallel) (longitudinal strain) values measured by 2D-STE could
      identify areas of MI (myocardial infarction) as determined by CE MRI (contrast
      enhanced magnetic resonance imaging). Conventional echocardiographic apical long
      axis recordings were performed in 38 patients, 9 months after a first MI. Peak
      systolic epsilon(parallel) measured by 2D-STE in 16 left ventricle segments was
      compared with segmental infarct mass and transmurality assessed by CE MRI.
      Segmental values were averaged to global and territorial values for assessment of
      global function and myocardial function in the coronary distribution areas. CE
      MRI identified transmural infarction in 27 patients, and a mean infarct size of
      36+/-25 g. Peak systolic epsilon( parallel) correlated with the infarct mass at
      the global level (r=0.84, P<0.001). A strain value of -15% identified infarction
      with 83% sensitivity and 93% specificity at the global level and 76% and 95% at
      the territorial level, and a strain value of -13% identified transmural
      infarction with 80% sensitivity and 83% specificity at the segmental level.
      Global infarct mass correlates with the wall motion score index (r=0.70,
      P<0.001), and left ventricular ejection fraction measured by MRI or
      echocardiography (r=-0.71 and -0.58, both P<0.001). In chronic infarction, peak
      systolic epsilon(parallel) measured by 2D-STE correlates with the infarct mass
      assessed by CE MRI at a global level, and separates infarcted from non-infarcted
      tissue. Global strain is an excellent predictor of myocardial infarct size in
      chronic ischaemic heart disease.

PMID- 17501721
TI  - NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS
      generation.
AB  - NOX4 is an enigmatic member of the NOX (NADPH oxidase) family of ROS (reactive
      oxygen species)-generating NADPH oxidases. NOX4 has a wide tissue distribution,
      but the physiological function and activation mechanisms are largely unknown, and
      its pharmacology is poorly understood. We have generated cell lines expressing
      NOX4 upon tetracycline induction. Tetracycline induced a rapid increase in NOX4
      mRNA (1 h) followed closely (2 h) by a release of ROS. Upon tetracycline
      withdrawal, NOX4 mRNA levels and ROS release decreased rapidly (<24 h). In
      membrane preparations, NOX4 activity was selective for NADPH over NADH and did
      not require the addition of cytosol. The pharmacological profile of NOX4 was
      distinct from other NOX isoforms: DPI (diphenyleneiodonium chloride) and
      thioridazine inhibited the enzyme efficiently, whereas apocynin and gliotoxin did
      not (IC(50)>100 muM). The pattern of NOX4-dependent ROS generation was unique:
      (i) ROS release upon NOX4 induction was spontaneous without need for a stimulus,
      and (ii) the type of ROS released from NOX4-expressing cells was H(2)O(2),
      whereas superoxide (O(2)(-)) was almost undetectable. Probes that allow detection
      of intracellular O(2)(-) generation yielded differential results: DHE
      (dihydroethidium) fluorescence and ACP (1-acetoxy-3-carboxy-2,2,5,5
      tetramethylpyrrolidine) ESR measurements did not detect any NOX4 signal, whereas
      a robust signal was observed with NBT. Thus NOX4 probably generates O(2)(-)
      within an intracellular compartment that is accessible to NBT (Nitro Blue
      Tetrazolium), but not to DHE or ACP. In conclusion, NOX4 has a distinct
      pharmacology and pattern of ROS generation. The close correlation between NOX4
      mRNA and ROS generation might hint towards a function as an inducible NOX
      isoform.

PMID- 17501722
TI  - Controlling ourselves: insights into the development of psychopathology.

PMID- 17501723
TI  - Annotation: what electrical brain activity tells us about brain function that
      other techniques cannot tell us - a child psychiatric perspective.
AB  - BACKGROUND: Monitoring brain processes in real time requires genuine subsecond
      resolution to follow the typical timing and frequency of neural events. Non
      invasive recordings of electric (EEG/ERP) and magnetic (MEG) fields provide this
      time resolution. They directly measure neural activations associated with a wide
      variety of brain states and processes, even during sleep or in infants. Mapping
      and source estimation can localise these time-varying activation patterns inside
      the brain. METHODS: Recent EEG/ERP research on brain functions in the domains of
      attention and executive functioning, perception, memory, language, emotion and
      motor processing in ADHD, autism, childhood-onset schizophrenia, Tourette
      syndrome, specific language disorder and developmental dyslexia, anxiety,
      obsessive-compulsive disorder, and depression is reviewed. RESULTS: Over the past
      two decades, electrophysiology has substantially contributed to the understanding
      of brain functions during normal development, and psychiatric conditions of
      children and adolescents. Its time resolution has been important to measure
      covert processes, and to distinguish cause and effect. CONCLUSIONS: In the
      future, EEG/ERP parameters will increasingly characterise the interplay of neural
      states and information processing. They are particularly promising tools for
      multilevel investigations of etiological pathways and potential predictors of
      clinical treatment response.

PMID- 17501724
TI  - Children's skin conductance reactivity as a mechanism of risk in the context of
      parental depressive symptoms.
AB  - BACKGROUND: Children's physiological reactivity was examined as a moderator of
      relations between parental dysphoria and child adjustment problems, addressing
      gaps in the study of child characteristics as risk processes. METHOD: One hundred
      fifty-seven children (86 boys, 71 girls) were assessed twice over a two-year
      interval. Skin conductance level reactivity (SCLR) to inter-adult argument and
      problem-solving tasks was observed. RESULTS: SCLR moderated longitudinal
      predictions of children's internalizing, externalizing and social adjustment
      problems, especially for paternal rather than maternal dysphoria. Higher SCLR
      predicted greater vulnerability to parental depressive symptomatology.
      CONCLUSIONS: Findings highlight that individual differences in children's
      physiological reactivity may relate to risk for adjustment problems in the
      context of parental depressive symptoms.

PMID- 17501725
TI  - Incentive-related modulation of cognitive control in healthy, anxious, and
      depressed adolescents: development and psychopathology related differences.
AB  - BACKGROUND: Developmental changes in cognitive and affective processes contribute
      to adolescent risk-taking behavior, emotional intensification, and
      psychopathology. The current study examined adolescent development of cognitive
      control processes and their modulation by incentive, in health and
      psychopathology. Predictions include 1) better cognitive control in adults than
      adolescents, and in healthy adolescents than anxious and depressed adolescents,
      and 2) a stronger influence of incentives in adolescents than adults, and in
      healthy adolescents than their depressed and anxious counterparts. METHODS:
      Antisaccadic eye movement parameters, which provide a measure of cognitive
      control, were collected during a reward antisaccade task that included
      parameterized incentive levels. Participants were 20 healthy adults, 30 healthy
      adolescents, 16 adolescents with an anxiety disorder, and 11 adolescents with
      major depression. Performance accuracy and saccade latency were analyzed to test
      both developmental and psychopathology hypotheses. RESULTS: Development and
      psychopathology group differences in cognitive control were found. Specifically,
      adults performed better than healthy adolescents, and healthy adolescents than
      anxious and depressed adolescents. Incentive improved accuracy for all groups;
      however, incremental increases were not sufficiently large to further modulate
      performance. Incentives also affected saccade latencies, pushing healthy
      adolescent latencies to adult levels, while being less effective in adolescents
      with depression or anxiety. This latter effect was partially mediated by anxiety
      symptom severity. CONCLUSIONS: Current findings evidence the modulation of
      cognitive control processes by incentives. While seen in both healthy adults and
      healthy adolescents, this modulatory effect was stronger in youth. While anxious
      and depressed adolescents exhibited improved cognitive control under incentives,
      this effect was smaller than that in healthy adolescents. These findings suggest
      differential incentive and/or cognitive control processing in anxiety and
      depression, and across development. Differences could result from disorder
      specific, or combined developmental and pathological mechanisms.

PMID- 17501726
TI  - The relationship between attention, executive functions and reading domain
      abilities in attention deficit hyperactivity disorder and reading disorder: a
      comparative study.
AB  - BACKGROUND: Co-morbidity of attention deficit hyperactivity disorder (ADHD) and
      reading disorder (RD) is frequent. The objective of this investigation was to
      assess the potential uniqueness of co-morbid ADHD + RD and extend existing
      findings to the Hebrew language. METHOD: A parallel group design with post-hoc
      analysis of group differences was employed comparing four groups of children (19
      ADHD, 17 RD, 27 ADHD + RD, and 23 controls) on reading measures, attention and
      executive functions (EF) as well as functions of phonemic awareness and rapid
      naming. Forward stepwise regressions were run in order to delineate significant
      relationships between phonemic awareness, rapid naming, attention and EF with
      outcome variables of reading. RESULTS: The co-morbid group shared the basic
      characteristic impairments in attention and executive functions with the pure
      ADHD group and in reading domain functions with the pure RD group. In addition,
      this group showed unique deficits in rapid naming and a more severe impairment in
      working memory. Forward stepwise regression pointed to associations between
      executive functions and word reading accuracy in children with ADHD, in contrast
      to associations between linguistic functions and word accuracy in non-ADHD.
      CONCLUSION: The combination of cognitive deficits in the subgroup of children
      with both ADHD and RD and the relationship between accuracy in word decoding and
      executive functions shown for the ADHD groups point to a distinct clinical
      profile of the co-morbid condition. Attention and EF should be considered in the
      diagnosis of RD and in the remediation protocol.

PMID- 17501727
TI  - Autistic traits in a population-based ADHD twin sample.
AB  - BACKGROUND: Most diagnostic nomenclatures do not allow for the concurrent
      diagnosis of autism and attention-deficit/hyperactivity disorder (ADHD). Clinic
      based studies suggest autistic symptoms are common in children with ADHD, but
      such studies are prone to referral bias. This study assesses whether children
      with ADHD selected from the general twin population have elevated levels of
      autistic traits. METHODS: Nine hundred forty-six twins identified by Missouri
      birth records were assigned to DSM-IV ADHD diagnoses and seven population-derived
      ADHD subtypes defined through latent class analysis of DSM-IV ADHD symptoms. The
      Social Responsiveness Scale (SRS) was used as a quantitative measure of autistic
      traits. Linear regression was used to evaluate whether mean SRS scores differed
      between ADHD diagnostic groups. RESULTS: Mean SRS scores for DSM-IV predominantly
      inattentive subtype and combined subtype ADHD groups were significantly higher
      than for subjects without DSM-IV ADHD (p < .001, both comparisons). Five of the
      population-derived ADHD subtypes (talkative-impulsive, mild and severe
      inattentive, mild and severe combined) had significantly higher mean SRS scores
      compared to the latent class subtype with few ADHD symptoms (p < .001, all
      comparisons). DSM-IV combined subtype and the population-derived severe combined
      subtype had the highest mean total SRS scores and the highest mean scores for
      each of the three autism symptom domains, with a substantial proportion of
      individuals scoring in the clinically significant range. CONCLUSIONS: This study
      provides population-based evidence for clinically significant elevations of
      autistic traits in children meeting diagnostic criteria for ADHD. These results
      have implications for the design and interpretation of studies of both disorders.

PMID- 17501728
TI  - The effectiveness of Picture Exchange Communication System (PECS) training for
      teachers of children with autism: a pragmatic, group randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of expert training and consultancy for
      teachers of children with autism spectrum disorder in the use of the Picture
      Exchange Communication System (PECS). METHOD:  DESIGN: Group randomised,
      controlled trial (3 groups: immediate treatment, delayed treatment, no
      treatment). PARTICIPANTS: 84 elementary school children, mean age 6.8 years.
      TREATMENT: A 2-day PECS workshop for teachers plus 6 half-day, school-based
      training sessions with expert consultants over 5 months. OUTCOME MEASURES: Rates
      of: communicative initiations, use of PECS, and speech in the classroom; Autism
      Diagnostic Observation Schedule-Generic (ADOS-G) domain scores for Communication
      and Reciprocal Social Interaction; scores on formal language tests. RESULTS:
      Controlling for baseline age, developmental quotient (DQ) and language; rates of
      initiations and PECS usage increased significantly immediately post-treatment
      (Odds Ratio (OR) of being in a higher ordinal rate category 2.72, 95% confidence
      interval 1.22-6.09, p < .05 and OR 3.90 (95%CI 1.75-8.68), p < .001,
      respectively). There were no increases in frequency of speech, or improvements in
      ADOS-G ratings or language test scores. CONCLUSIONS: The results indicate modest
      effectiveness of PECS teacher training/consultancy. Rates of pupils' initiations
      and use of symbols in the classroom increased, although there was no evidence of
      improvement in other areas of communication. TREATMENT effects were not
      maintained once active intervention ceased.

PMID- 17501729
TI  - Eye-witness memory and suggestibility in children with Asperger syndrome.
AB  - BACKGROUND: Individuals with autism spectrum disorders (ASD) present with a
      particular profile of memory deficits, executive dysfunction and impaired social
      interaction that may raise concerns about their recall and reliability in
      forensic and legal contexts. Extant studies of memory shed limited light on this
      issue as they involved either laboratory-based tasks or protocols that varied
      between participants. METHOD: The current study used a live classroom event to
      investigate eye-witness recall and suggestibility in children with Asperger
      syndrome (AS group; N = 24) and typically developing children (TD group; N = 27).
      All participants were aged between 11 and 14 years and were interviewed using a
      structured protocol. Two measures of executive functioning were also
      administered. RESULTS: The AS group were found to be no more suggestible and no
      less accurate than their peers. However, free recall elicited less information,
      including gist, in the AS group. TD, but not AS, participants tended to focus on
      the socially salient aspects of the scene in their free recall. Both general and
      specific questioning elicited similar numbers of new details in both groups.
      Significant correlations were found between memory recall and executive
      functioning performance in the AS group only. CONCLUSIONS: The present study
      indicates that children with AS can act as reliable witnesses but they may be
      more reliant on questioning to facilitate recall. Our findings also provide
      evidence for poor gist memory. It is speculated that such differences stem from
      weak central coherence and lead to a reliance on generic cognitive processes,
      such as executive functions, during recall. Future studies are required to
      investigate possible differences in compliance, rates of forgetting and false
      memory.

PMID- 17501730
TI  - Association between nonmaternal care in the first year of life and children's
      receptive language skills prior to school entry: the moderating role of
      socioeconomic status.
AB  - BACKGROUND: Studies have suggested that nonmaternal care (NMC) may either carry
      risks or be beneficial for children's language development. However, few tested
      the possibility that NMC may be more or less protective for children with
      different family backgrounds. This study investigates the role of the family
      environment, as reflected in the socioeconomic status (SES), in the association
      between NMC in the first year of life and children's receptive language skills
      prior to school entry. METHOD: A representative sample of 2,297 Canadian children
      aged between 0 and 11 months at their first assessment was followed over 4 years.
      Receptive language skills were assessed with the Peabody Picture Vocabulary Test
      Revised (PPVT-R) when the child was 4 to 5 years old. RESULTS: After controlling
      for selection factors, SES was found to moderate the association between NMC and
      receptive language skills: Full-time NMC in the first year of life was associated
      with higher PPVT-R scores among children from low SES families (d = .58), but not
      among children from adequate SES families. CONCLUSION: Full-time NMC in infancy
      may contribute to reducing the cognitive inequalities between children of low and
      adequate SES.

PMID- 17501731
TI  - Developmental course of psychopathology in youths with and without intellectual
      disabilities.
AB  - BACKGROUND: We aimed to describe similarities and differences in the
      developmental course of psychopathology between children with and without
      intellectual disabilities (ID). METHODS: Multilevel growth curve analysis was
      used to analyse the developmental course of psychopathology, using the Child
      Behavior Checklist (CBCL), in two longitudinal multiple-birth-cohort samples of 6
      to 18-year-old children with ID (N = 978) and without ID (N = 2,047) using three
      repeated measurements across a 6-year period. RESULTS: Children with ID showed a
      higher level of problem behaviours across all ages compared to children without
      ID. A significant difference between the samples in the developmental courses was
      found for Aggressive Behaviour and Attention Problems, where children with ID
      showed a significantly larger decrease. Gender differences in the development of
      psychopathology were similar in both samples, except for Social Problems where
      males with ID showed a larger decrease in problem behaviour across time than
      females with ID and males and females without ID. CONCLUSIONS: Results indicate
      that children with ID continue to show a greater risk for psychopathology
      compared to typically developing children, although this higher risk is less
      pronounced at age 18 than it is at age 6 for Aggressive Behaviour. Contrary to
      our expectations, the developmental course of psychopathology in children with ID
      was quite similar from age 6 to 18 compared to children without ID. The normative
      developmental trajectories of psychopathology in children with ID, presented
      here, can serve as a yardstick against which development of childhood
      psychopathology can be detected as deviant.

PMID- 17501732
TI  - Continuity of functional-somatic symptoms from late childhood to young adulthood
      in a community sample.
AB  - BACKGROUND: The goal of this study was to assess the course of functional-somatic
      symptoms from late childhood to young adulthood and the associations of these
      symptoms with young adult psychopathology. METHODS: Data were collected in a
      large community sample at three different points in time (1994, 1997, and 2001).
      Functional-somatic symptoms were represented by nine self-reported items of the
      Youth Self Report (YSR) or the Young Adult Self Report (YASR). Only definite
      expressions of these symptoms were counted. RESULTS: Definite functional-somatic
      symptoms across time ranged between 1.0 and 2.6% for dizziness, 3.0 and 6.7% for
      overtiredness, 1.0 and 2.9% for aches and pains, 5.6 and 8.3% for headaches, 1.2
      and 1.9% for nausea, 2.5 and 3.0% for stomach-ache, and .2 and .8% for vomiting.
      In general, symptoms were more common in females at various times. In high
      scoring subjects there was a significantly higher chance of functional-somatic
      symptoms persisting across time. CONCLUSIONS: Functional-somatic symptoms in
      childhood and adolescents can be easily identified in the community. In high
      scoring subjects they tend to persist from childhood to adulthood.

PMID- 17501733
TI  - Pacific Islands Families Study: behavioral problems among two-year-old Pacific
      children living in New Zealand.
AB  - BACKGROUND: The aim of this study was to determine (1) the prevalence of
      behavioral problems among two-year-old Pacific children living in New Zealand,
      (2) ethnic differences in behavioral problems, and (3) relationships between
      maternal and socio-demographic variables and problem child behavior. METHODS:
      Data were gathered from the Pacific Islands Families (PIF) Study. Mothers of a
      cohort of 1398 Pacific infants born in Auckland, New Zealand during 2000 were
      interviewed when the children were two years of age. Maternal reports (1028) of
      child behavior were obtained using the Child Behavior Checklist (CBCL). RESULTS:
      In the PIF cohort, 15.6% of children were in the clinical range with one or more
      deviant scores from the seven syndrome scales, and 14% were in the borderline
      range. The prevalence rate of internalizing problems was 17.1% in the clinical
      range and 8.9% in the borderline range. The prevalence rate of externalizing
      problems was 6.6% in the clinical range and 13.7% in the borderline range. The
      prevalence rate of total problems was 14.2% in the clinical range and 9.6% in the
      borderline range. Discipline and maternal education were significantly associated
      with elevated externalizing scores. Household size, maternal education, cultural
      orientation, and number of years living in New Zealand were significantly
      associated with internalizing scores. Child ethnicity was significantly
      associated with internalizing, externalizing and total problem behavior scores.
      In the clinical range, child ethnicity and gender were significantly associated
      with the prevalence of problem behavior. CONCLUSIONS: Cross-ethnicity differences
      in CBCL scores were found, which illustrates the diversity in the Pacific
      population in New Zealand. Such findings highlight the way in which preschool
      behavior problems may vary within specific cultural settings and underscore the
      need for in-depth research to explore these unique contexts.

PMID- 17501736
TI  - Yersinia ruckeri infections in salmonid fish.
AB  - Yersinia ruckeri is the causative agent of yersiniosis or enteric redmouth
      disease leading to significant economic losses in salmonid aquaculture worldwide.
      Infection may result in a septicaemic condition with haemorrhages on the body
      surface and in the internal organs. Despite the significance of the disease, very
      little information is available on the pathogenesis, hampering the development of
      preventive measures to efficiently combat this bacterial agent. This review
      discusses the agent and the disease it causes. The possibility of the presence of
      similar virulence markers and/or pathogenic mechanisms between the Yersinia
      species which elicit disease in humans and Y. ruckeri is also examined.

PMID- 17501737
TI  - Susceptibility of salmonid alphavirus to a range of chemical disinfectants.
AB  - A range of commercially available disinfectants were tested for efficacy against
      salmonid alphavirus under a range of different conditions including variations in
      concentration, temperature, contact time, water type and presence or absence of
      organic matter. Testing was based on the protocol defined in the draft European
      Standard prEN 14675, for which the effective standard is a 4 log(10) reduction in
      viral titre. All disinfectants were found to be effective under at least some of
      the conditions tested. However, the presence of organic matter in particular was
      shown to be detrimental in some cases, either through rendering some
      disinfectants ineffective, or by production of a visible inhomogeneity.

PMID- 17501738
TI  - Idiopathic muscle necrosis in the Norway lobster, Nephrops norvegicus (L.):
      aetiology, pathology and progression to bacteraemia.
AB  - The pathology and progression of idiopathic muscle necrosis (IMN) in Nephrops
      norvegicus and possible aetiologies have been investigated. Trawl capture, aerial
      exposure and handling initiate IMN, and the condition can be induced through
      periods of aerial exposure alone, in the absence of trawling. Within 24-48 h
      after trawl capture IMN progresses to a multi-species bacterial septicaemia, with
      moribund animals exhibiting clinical signs. The aetiology of this condition has
      been examined using molecular (16S rRNA gene sequencing) and biochemical
      (standard taxonomic assays, Biolog) criteria to characterize bacterial isolates
      from moribund and healthy animals. Histopathology of the IMN phase reveals a loss
      of sarcomeric structure with necrotic lesions containing pyknotic nuclei,
      fragments of myofibrils and connective tissue elements. In the bacterial phase
      there is extensive loss of abdominal muscle structure, and the presence of rod
      shaped Gram-negative bacteria in the degrading tissues. The results demonstrate
      that the IMN condition is connected to stressful conditions imposed on N.
      norvegicus, but involves no pathogenic agents. This is followed by an
      opportunistic bacterial infection that causes further tissue spoilage. It is
      believed that the primary cause of both IMN and bacteraemia is imposed stress,
      but they are expressed in different time courses.

PMID- 17501739
TI  - Dominant pathogenic species of mesophilic aeromonads isolated from diseased and
      healthy fish cultured in Poland.
AB  - Aeromonas isolates were collected from cultured fish, characterized
      phenotypically and identified to species using 16S rDNA. The pathogenicity of all
      isolates was assayed on the basis of haemolytic and proteolytic activity and
      challenge tests were performed for isolates from healthy fish. A total of 131
      Aeromonas isolates were obtained and identified as follows: A. hydrophila (13),
      A. bestiarum (23), A. salmonicida (motile biogroup) (19), A. caviae (2), A.
      sobria (18), A. veronii bt. sobria (42), A. jandaei (1), A. encheleia (11) and A.
      allosaccharophila (2). All isolates of A. hydrophila and A. bestiarum and most
      isolates of A. salmonicida and A. veronii were classified as pathogenic.
      Aeromonas hydrophila was isolated only from diseased trout except for one isolate
      obtained from carp fry. The other potentially pathogenic Aeromonas species were
      present in diseased as well as healthy fish. The pathogenicity of isolates from
      healthy fish was correlated with their enzymatic activity and was also tested by
      challenge experiments. The dominant pathogenic species were A. veronii bt.
      sobria, A. bestiarum and A. salmonicida in common carp and A. hydrophila in
      rainbow trout.

PMID- 17501740
TI  - Experimental infection of turbot, Psetta maxima (L.), with strains of viral
      haemorrhagic septicaemia virus isolated from wild and farmed marine fish.
AB  - The susceptibility of turbot, Psetta maxima, to infection with two strains of
      viral haemorrhagic septicaemia virus (VHSV) obtained from wild Greenland halibut,
      Reinhardtius hippoglossoides, and from farmed turbot was examined. A marine VHSV
      strain known to be highly pathogenic for turbot was also utilized for comparative
      purposes. Fish were infected by intra-peritoneal (i.p.), immersion or
      cohabitation, and maintained at two different temperatures (8 and 15 degrees C).
      Infection trials showed that the three VHSV isolates were pathogenic for turbot
      fingerlings by i.p. injection at both temperatures, with high levels of
      mortality. Virus was recovered from most pools of dead fish i.p. challenged, but
      not from surviving fish. Although clinical signs were not induced following
      waterborne exposure, viral growth was obtained from some pools of surviving fish
      challenged by immersion with strain GH40 from Greenland halibut, which indicates
      that the virus can survive in sea water and infect other fish via horizontal
      transmission. Furthermore, although low, the clinical signs and mortality
      observed in fish cohabitating with turbot challenged with strain GH40 confirms
      horizontal transmission and indicates that the passage through fish increases the
      virulence of this strain for turbot. These findings indicate that Greenland
      halibut, as other wild fish, may play an important role in the epizootiology of
      VHSV and suggest a potential risk for the turbot farming industry.

PMID- 17501741
TI  - Atypical Aeromonas salmonicida infection in naturally- and laboratory-challenged
      farmed haddock, Melanogrammus aeglefinus (L.).

PMID- 17501743
TI  - The earliest fossil embryos begin to mature.

PMID- 17501744
TI  - Developmental transcriptional-competence model for a histone variant and a
      unicellular origin scenario for transcriptional-multipotency mechanisms.

PMID- 17501745
TI  - Homeodomain proteins belong to the ancestral molecular toolkit of eukaryotes.
AB  - Multicellular organization arose several times by convergence during the
      evolution of eukaryotes (e.g., in terrestrial plants, several lineages of
      "algae," fungi, and metazoans). To reconstruct the evolutionary transitions
      between unicellularity and multicellularity, we need a proper understanding of
      the origin and diversification of regulatory molecules governing the construction
      of a multicellular organism in these various lineages. Homeodomain (HD) proteins
      offer a paradigm for studying such issues, because in multicellular eukaryotes,
      like animals, fungi and plants, these transcription factors are extensively used
      in fundamental developmental processes and are highly diversified. A number of
      large eukaryote lineages are exclusively unicellular, however, and it remains
      unclear to what extent this condition reflects their primitive lack of "good
      building blocks" such as the HD proteins. Taking advantage from the recent burst
      of sequence data from a wide variety of eukaryote taxa, we show here that HD
      containing transcription factors were already existing and diversified (in at
      least two main classes) in the last common eukaryote ancestor. Although the
      family was retained and independently expanded in the multicellular taxa, it was
      lost in several lineages of unicellular parasites or intracellular symbionts. Our
      findings are consistent with the idea that the common ancestor of eukaryotes was
      complex in molecular terms, and already possessed many of the regulatory
      molecules, which later favored the multiple convergent acquisition of
      multicellularity.

PMID- 17501746
TI  - Surprisingly complex T-box gene complement in diploblastic metazoans.
AB  - Ctenophores and cnidarians are two metazoan groups that evolved at least 600 Ma,
      predating the Cambrian explosion. Although both groups are commonly categorized
      as diploblastic animals without derivatives of the mesodermal germ layer,
      ctenophores possess definitive contractile "muscle" cells. T-box family
      transcription factors are an evolutionarily ancient gene family, arising in the
      common ancestor of metazoans, and have been divided into eight groups in five
      distinct subfamilies, many of which are involved in the specification of
      mesodermal as well as ectodermally and endodermally derived structures. Here, we
      report the cloning and expression of five T-box genes from a ctenophore,
      Mnemiopsis leidyi. Phylogenetic analyses demonstrated that ctenophores possess
      members of at least three of the five T-box subfamilies, and expression studies
      suggested distinct roles of each T-box genes during gastrulation and early
      organogenesis. Moreover, genome searches of the sea anemone, Nematostella
      vectensis (anthozoan cnidarian), showed at least 13 T-box genes in Nematostella,
      which are divided into at least six distinct groups in the same three subfamilies
      found in ctenophores. Our results from two diploblastic animals indicate that the
      common ancestor of eumetazoans had a complex set of T-box genes and that two
      distinct subfamilies might have appeared during triploblastic evolution.

PMID- 17501747
TI  - Histone H2A.Z expression in two indirectly developing marine invertebrates
      correlates with undifferentiated and multipotent cells.
AB  - The embryos of indirect developers generate an intermediate larval stage that
      nourishes the proliferation of undifferentiated multipotent cell precursors in
      charge of postembryonic adult formation. Multipotency affects the regulation of
      many genes and seems to be mediated in part by chromatin modification. Chromatin
      transcriptional properties are regulated by histone modification and by
      incorporation of peculiar histone variants. The histone variant H2A.Z is
      associated with transcriptionally competent chromatin and silent genes primed for
      activation or permanent repression. However, despite the extensive mechanistic
      characterizations in unicellular eukaryotes, the essential role of the highly
      conserved H2A.Z variant during animal embryogenesis remains obscure. We show that
      the expression of H2A.Z in the larvae of two distant indirectly developing marine
      invertebrates, a polychaete and a sea urchin, remains high in all their embryonic
      and postembryonic developmentally competent cell precursors, and declines during
      their differentiation. In particular, the expression in undifferentiated
      multipotent adult precursors during feeding larval stages in both organisms
      provides unique insight about its general association with developmental
      potential. Our experiments confirm previous reports indicating that the
      expression of H2A.Z is proliferation (DNA synthesis) independent, in contrast
      with the DNA synthesis dependence of "mainstream" histones. We suggest that
      similar H2A.Z transcriptional functions previously identified in unicellular
      organisms also help to maintain an open chromatin state competent for
      transcriptional-regulatory transactions during metazoan development.

PMID- 17501748
TI  - Developmental origin of the adult nervous system in a holothurian: an attempt to
      unravel the enigma of neurogenesis in echinoderms.
AB  - In adult echinoderms, the nervous system includes the ectoneural and hyponeural
      subsystems. The former has been believed to develop from the ectoderm, whereas
      the latter is considered to be mesodermal in origin. However, this view has not
      been substantially supported by embryological examinations. Our study deals with
      the developmental origin of the nervous system in the direct-developing sea
      cucumber Eupentacta fraudatrix. The rudiment of the adult nervous system develops
      from ectodermally derived cells, which ingress into the primary body cavity from
      the floor of the vestibule. At the earliest stages, only the rudiment of the
      ectoneural nerve ring is laid down. The radial nerve cords and tentacular nerves
      grow out from this subcutaneous rudiment. The ectoneural cords do not develop
      simultaneously but make their appearance in the following order: unpaired mid
      ventral cord, paired dorsal lateral cords, and ventral lateral cords. These
      transitional developmental stages probably recapitulate the evolution of the
      echinoderm body plan. The holothurian hyponeural subsystem, as other regions of
      the metazoan nervous system, has an ectodermal origin. It originally appears as a
      narrow band of tissue, which bulges out of the basal region of the ectoneural
      neuroepithelium. Our data combined with those of other workers strongly suggest
      that the adult nervous tissue in echinoderms develops separately from the
      superficial larval system of ciliary nerves. Therefore, our data are neither in
      strict accordance with Garstang's hypothesis nor do they allow to refuse it.
      Nevertheless, in addition to ciliary bands, other areas of neurogenetic epidermis
      must be taken into account.

PMID- 17501749
TI  - Evolutionary modification of mesenchyme cells in sand dollars in the transition
      from indirect to direct development.
AB  - Peronella japonica, an intermediate type of direct-developing sand dollar, forms
      an abbreviated pluteus, followed by metamorphosis within 3 days without feeding.
      In this species, ingression of mesenchyme cells starts before hatching and
      continues until gastrulation, but no typical secondary mesenchyme cells (SMCs)
      migrate from the tip of the archenteron. Here, I investigated the cell lineage of
      mesenchyme cells through metamorphosis in P. japonica and found that mesenchyme
      cells migrating before hatching (early mesenchyme cells [EMCs]) were exclusively
      derived from micromeres and became larval skeletogenic cells, whereas cells
      migrating after hatching (late mesenchyme cells [LMCs]) appeared to contain
      several nonskeletogenic cells. Thus, it is likely that EMCs are homologous to
      primary mesenchyme cells (PMCs) and LMCs are similar to the SMCs of typical
      indirect developers, suggesting that heterochrony in the timing of mesenchyme
      cell ingression may have occurred in this species. EMCs disappeared after
      metamorphosis and LMCs were involved in adult skeletogenesis. Embryos from which
      micromeres were removed at the 16-cell stage formed armless plutei that went on
      to form adult skeletons and resulted in juveniles with normal morphology. These
      results suggest that in P. japonica, LMCs form adult skeletal elements, whereas
      EMCs are specialized for larval spicule formation. The occurrence of evolutionary
      modifications in mesenchyme cells in the transition from indirect to direct
      development of sand dollars is discussed.

PMID- 17501750
TI  - Evidence that a late-emerging population of trunk neural crest cells forms the
      plastron bones in the turtle Trachemys scripta.
AB  - The origin of the turtle plastron is not known, but these nine bones have been
      homologized to the exoskeletal components of the clavicles, the interclavicular
      bone, and gastralia. Earlier evidence from our laboratory showed that the bone
      forming cells of the plastron were positive for HNK-1 and PDGFRalpha, two markers
      of the skeletogenic neural crest. This study looks at the embryonic origin of
      these plastron-forming cells. We show that the HNK-1+ cells are also positive for
      p75 and FoxD3, confirming their neural crest identity, and that they originate
      from the dorsal neural tube of stage 17 turtle embryos, several days after the
      original wave of neural crest cells have migrated and differentiated. DiI studies
      show that these are migratory cells, and they can be observed in the lateral
      regions of the embryo and can be seen forming intramembranous bone in the ventral
      (plastron) regions. Before migrating ventrally, these late-emerging neural crest
      cells reside for over a week in a carapacial staging area above the neural tube
      and vertebrae. It is speculated that this staging area is where they lose the
      inability to form skeletal cells.

PMID- 17501751
TI  - Modular evolution of the Cetacean vertebral column.
AB  - Modular theory predicts that hierarchical developmental processes generate
      hierarchical phenotypic units that are capable of independent modification. The
      vertebral column is an overtly modular structure, and its rapid phenotypic
      transformation in cetacean evolution provides a case study for modularity.
      Terrestrial mammals have five morphologically discrete vertebral series that are
      now known to be coincident with Hox gene expression patterns. Here, I present the
      hypothesis that in living Carnivora and Artiodactyla, and by inference in the
      terrestrial ancestors of whales, the series are themselves components of larger
      precaudal and caudal modular units. Column morphology in a series of fossil and
      living whales is used to predict the type and sequence of developmental changes
      responsible for modification of that ancestral pattern. Developmental innovations
      inferred include independent meristic additions to the precaudal column in basal
      archaeocetes and basilosaurids, stepwise homeotic reduction of the sacral series
      in protocetids, and dissociation of the caudal series into anterior tail and
      fluke subunits in basilosaurids. The most dramatic change was the novel
      association of lumbar and anterior caudal vertebrae in a module that crosses the
      precaudal/caudal boundary. This large unit is defined by shared patterns of
      vertebral morphology, count, and size in all living whales (Neoceti).

PMID- 17501752
TI  - Cranial modularity and sequence heterochrony in mammals.
AB  - Heterochrony, the temporal shifting of developmental events relative to each
      other, requires a degree of autonomy among those processes or structures.
      Modularity, the division of larger structures or processes into autonomous sets
      of internally integrated units, is often discussed in relation to the concept of
      heterochrony. However, the relationship between the developmental modules derived
      from studies of heterochrony and evolutionary modules, which should be of
      adaptive importance and relate to the genotype-phenotype map, has not been
      explicitly studied. I analyzed a series of sectioned and whole cleared-and
      stained embryological and neonatal specimens, supplemented with published
      ontogenetic data, to test the hypothesis that bones within the same phenotypic
      modules, as determined by morphometric analysis, are developmentally integrated
      and will display coordinated heterochronic shifts across taxa. Modularity was
      analyzed in cranial bone ossification sequences of 12 therian mammals. A dataset
      of 12-18 developmental events was used to assess if modularity in developmental
      sequences corresponds to six phenotypic modules, derived from a recent
      morphometric analysis of cranial modularity in mammals. Kendall's tau was used to
      measure rank correlations, with randomization tests for significance. If
      modularity in developmental sequences corresponds to observed phenotypic modules,
      bones within a single phenotypic module should show integration of developmental
      timing, maintaining the same timing of ossification relative to each other,
      despite differences in overall ossification sequences across taxa. Analyses did
      not find any significant conservation of developmental timing within the six
      phenotypic modules, meaning that bones that are highly integrated in adult
      morphology are not significantly integrated in developmental timing.

PMID- 17501753
TI  - Developmental capacitance, genetic accommodation, and adaptive evolution.
AB  - The concept of genetic accommodation remains controversial, in part because it
      remains unclear whether evolution by genetic accommodation forces a revolution,
      or merely a shift in emphasis, in our understanding of how evolution produces
      adaptive new traits. Here I outline a perspective that largely favors the latter
      view. I argue that evolution by genetic accommodation can easily be integrated
      into traditional evolutionary concepts. At the same time, evolution by genetic
      accommodation invites novel empirical and theoretical approaches that may allow
      biologists to push the boundaries of our current understanding of the process of
      evolution and to solve some long-standing controversies. Specifically, I discuss
      the role of developmental mechanisms as natural, and likely ubiquitous,
      capacitors of cryptic genetic variation, and the role of environmental
      perturbations as mechanisms by which such variation can become visible to
      selection on an individual to population-wide scale. I argue that in combination,
      developmental capacitance and large-scale environmental perturbations have the
      potential to facilitate rapid evolution including the origin of novel adaptive
      features while circumventing otherwise powerful genetic and population-biological
      constraints on adaptive evolution. I end by highlighting several promising
      avenues for future empirical research to explore the mechanisms and significance
      of evolution by genetic accommodation.

PMID- 17501755
TI  - Attitudes and use of rubber dam by Irish general dental practitioners.
AB  - AIM: To investigate the attitudes towards and use of rubber dam by Irish general
      dental practitioners. METHODOLOGY: A pre-piloted questionnaire was distributed
      amongst a group of 600 dentists randomly selected from the Irish Register of
      Dentists. Replies from dentists working in specialist practice or the hospital
      dental service were excluded. Dentists were surveyed in relation to their use of
      rubber dam during a variety of operative and root canal treatments, as well as
      their attitudes to the use of rubber dam in dental practice. RESULTS: A total of
      300 replies were considered from a total of 324 that were received. Seventy-seven
      per cent of respondents (n=231) worked in general dental practice and 23% (n=69)
      worked in the Irish Health Board/Community Dental Service. Rubber dam was 'never'
      used by 77% of respondents (n=228) when placing amalgam restorations in posterior
      teeth, 52% (n=147) when placing composite restorations in posterior teeth, and
      59% (n=177) when placing composite restorations in anterior teeth. Rubber dam was
      'never' used by 39% of respondents (n=114) when performing root canal treatment
      on anterior teeth; 32% (n = 84) when performing root canal treatment on premolar
      teeth; and 26% (n=51) when performing root canal treatment on molar teeth. Fifty
      seven per cent (n=171) considered rubber dam 'cumbersome and difficult to apply',
      and 41% (n=123) considered throat pack 'as good a prevention against inhalation
      of endodontic instruments as rubber dam'. CONCLUSIONS: Whilst rubber dam is used
      more frequently for root canal treatment than operative treatment, its use is
      limited. This presents quality issues, as well as medico-legal and safety
      concerns for both the profession and patients.

PMID- 17501758
TI  - Critical role of ribavirin for the achievement of early virological response to
      HCV therapy in HCV/HIV-coinfected patients.
AB  - The response to hepatitis C virus (HCV) therapy seems to be lower in HCV/HIV
      coinfected patients than in HCV-monoinfected individuals. Given that most pivotal
      trials conducted in coinfected patients have used the combination of pegylated
      interferon (pegIFN) along with fixed low doses (800 mg/day) of ribavirin (RBV),
      it is unclear whether HIV itself and/or suboptimal RBV exposure could explain
      this poorer outcome. Two well-defined end points of early virological response
      were evaluated in Peginterferon Ribavirina Espana Coinfeccion (PRESCO), a
      multicentre trial in which the combination of pegIFN plus RBV (1000 mg if body
      weight <75 kg and 1200 mg if >75 kg) was prescribed to coinfected patients. For
      comparisons, we used unpublished data from early kinetics in two other large
      trials, one performed in HIV-negative patients [Pegasys International Study Group
      (PISG)] in which RBV 1000-1200 mg/day was used and another [AIDS Pegasys
      Ribavirin Coinfection Trial (APRICOT)] in which HIV-positive patients received
      fixed low RBV doses (800 mg/day). A total of 348 HCV/HIV-coinfected patients from
      the PRESCO trial were analysed as well as all patients treated with pegIFN plus
      RBV, who completed 12 weeks of therapy in the comparative studies (435 in PISG
      and 268 in APRICOT). Negative serum HCV-RNA at week 4 (which has the highest
      positive predictive value of sustained virological response, SVR) was attained in
      33.3%, 31.2% and 13% of treated patients with HCV genotype 1, respectively, in
      PRESCO, PISG and APRICOT. For HCV genotypes 2/3, responses were 83.7%, 84.2% and
      37%, respectively. A decline lower than 2 log(10) at week 12 (which has the
      highest negative predictive value of SVR) was seen in 25.5%, 19.5% and 37% of HCV
      genotype-1-infected patients, and in 2.1%, 2.9% and 12% of genotypes-2/3-infected
      patients, respectively. Prescription of high RBV doses enhances the early
      virological response to HCV therapy in HCV/HIV-coinfected patients, with results
      approaching those seen in HCV-monoinfected patients.

PMID- 17501757
TI  - Therapeutic issues in HIV/HCV-coinfected patients.
AB  - The importance of treating hepatitis C virus (HCV)-associated morbidities in a
      growing population of patients coinfected with human immunodeficiency virus (HIV)
      has increased since the introduction of highly active antiretroviral therapy. As
      a result, investigative attention is turning to HCV-related liver disease and
      treatment-associated issues in coinfection. HIV/HCV-coinfected patients have
      higher HCV RNA loads and show more rapid progression of fibrosis than do
      monoinfected patients. Combination therapy with pegylated interferon plus
      ribavirin (RBV) is the standard of care for HCV in coinfected patients. Therapy
      slows fibrosis progression, but toxicity prevents identification of the most
      effective RBV dose. Coinfected patients have about a threefold greater risk of
      antiretroviral therapy-associated hepatotoxicity than patients with HIV only.
      Other challenges include anaemia, mitochondrial toxicity, drug-drug interactions
      and leucopenia. Thus, chronic hepatitis C should be treated in HIV/HCV-coinfected
      patients, but steps must be taken to prevent and treat potential toxicities. The
      first European Consensus Conference on the Treatment of Chronic Hepatitis B and C
      in HIV Co-infected Patients was held March 2005 in Paris to address these issues.
      This article reviews the peer-reviewed literature and expert opinion published
      from 1990 to 2005, and compares results with presentations and recommendations
      from the Consensus Conference to best present current issues in coinfection.

PMID- 17501759
TI  - Clearance of hepatitis C virus in HIV-infected patients with multiple chronic
      viral hepatitis.
AB  - Viral interferences between hepatitis C (HCV) and hepatitis B (HBV) viruses were
      investigated in a case-control study conducted in 107 human immunodeficiency
      virus (HIV)-infected patients with HCV antibodies. Overall, 15 (68%) of 22
      hepatitis B surface antigen (HBsAg)-positive patients had negative serum HCV-RNA
      while it occurred in only nine (10%) of 85 HBsAg-negative counterparts (P =
      0.02). After adjusting for age, antiretroviral therapy, plasma HIV-RNA and CD4
      counts, being HBsAg-positive was strongly associated with having negative serum
      HCV-RNA (odds ratio: 23; 95% confidence interval: 6-59; P < 0.001). Thus, HBV may
      favour the elimination of HCV in HIV-infected patients, which may influence liver
      disease and therapeutic decisions.

PMID- 17501760
TI  - Pharmacokinetics and enhanced PKR response in patients with chronic hepatitis C
      treated with pegylated interferon alpha-2b and ribavirin.
AB  - This study investigated the molecular and pharmacokinetic mechanisms of the
      enhanced antiviral efficacy associated with pegylated interferon (PEG-IFN) alpha
      2b and ribavirin. The study involved comparing the expression of serial double
      stranded RNA-activated protein kinase (PKR) before and during treatment in 26 PEG
      IFN alpha-2b and 26 conventional IFN alpha-2b recipients matched for age, body
      weight and dose of ribavirin. The pharmacokinetics of PEG-IFN alpha-2b and
      ribavirin was analysed in 15 of the 26 PEG-IFN recipients. There was a rapid
      increase in PKR expression in both treatment groups, although expression from day
      2 onwards was maintained at a significantly higher level in the PEG-IFN
      recipients (P < 0.05). C(max) of PEG-IFN occurred 12-48 h after the initial
      administration, with t(1/2) and C(min) being 49 h and 190 pg/mL, respectively. In
      contrast to ribavirin, accumulation of PEG-IFN was minimal. There was no
      association between serum PEG-IFN and ribavirin levels and virological response.
      Although baseline expression of PKR before treatment was marginally higher in
      nonresponders (NRs), from day 2 onwards, sequential PKR expression in response to
      PEG-IFN was higher in sustained viral responders compared with the NRs (P <
      0.05). Significant correlations were found between kinetics of PKR expression and
      viral decline rates in each phase of hepatitis C virus dynamics (first phase, r =
      0.67, P = 0.0006; second phase, r = 0.67, P = 0.001). In conclusion, improvement
      in pharmacokinetics following pegylation led to higher intracellular PKR
      expression, which was associated with enhanced virological efficacy of PEG-IFN
      based combination therapy. The concentrations of both ribavirin and PEG-IFN alpha
      2b were not associated with viral response and PKR expression.

PMID- 17501761
TI  - Impaired ability of interferon-alpha-primed dendritic cells to stimulate Th1-type
      CD4 T-cell response in chronic hepatitis C virus infection.
AB  - In interferon-alpha (IFN-alpha)/ribavirin combination therapy for chronic
      hepatitis C (CHC), an enhanced T helper 1 (Th1) response is essential for the
      eradication of hepatitis C virus (HCV). We aimed to elucidate the role of IFN
      alpha or IFN-alpha/ribavirin in dendritic cell (DC) ability to induce Th1
      response in HCV infection. We generated monocyte-derived DC from 20 CHC patients
      and 15 normal subjects driven by granulocyte-macrophage colony-stimulating factor
      and interleukin 4 (IL-4) without IFN-alpha (GM/4-DC), with IFN-alpha (IFN-DC),
      with ribavirin (R-DC) or with IFN-alpha/ribavirin (IFN/R-DC) and compared their
      phenotypes and functions between the groups. We also compared them in 14 CHC
      patients between who subsequently attained sustained virological response (SVR)
      and who did not (non-SVR) by 24 weeks of IFN-alpha/ribavirin therapy. Compared
      with GM/4-DC, IFN-DC displayed higher CD86 expression, but lesser ability to
      secrete IL-10 and were more potent to prime CD4(+) T cells to secrete IFN-gamma
      and IL-2. Such differences were more significant in healthy subjects than in CHC
      patients. No additive effect of ribavirin was observed in DC phenotypes and
      functions in vitro either which was used alone or in combined with IFN-alpha.
      However, in the SVR patients, an ability of IFN/R-DC to prime T cells to secrete
      IFN-gamma and IL-2 was higher than those of IFN-DC and those of IFN/R-DC in the
      non-SVR group, respectively. In conclusion, DC from CHC patients are impaired in
      the ability to drive Th1 in response to IFN-alpha. Such DC impairment is restored
      in vitro by the addition of ribavirin in not all but some patients who cleared
      HCV by the combination therapy.

PMID- 17501762
TI  - High incidence of hepatitis C virus reinfection within a cohort of injecting drug
      users.
AB  - A retrospective cohort study was established of injecting drug users (IDUs) to
      assess evidence for hepatitis C virus (HCV) protective immunity through a
      comparison of incidence of initial HCV infection and HCV reinfection. Incidence
      of initial HCV infection was determined among HCV seronegative IDUs, and HCV
      reinfection determined among IDUs with newly acquired HCV infection, HCV viraemia
      and subsequent HCV RNA clearance. Serum was available for HCV RNA analysis from
      stored samples taken at the time of prior blood-borne virus screening. Potential
      HCV reinfection was defined as a positive HCV RNA following at least one negative
      HCV RNA. Incidence of initial HCV infection was 17/100 person-years (95% CI, 14
      20/100 person-years). The incidence of potential HCV reinfection was 42/100
      person-years (95% CI, 25-61/100 person-years), and after excluding cases without
      a change in HCV genotype and less than three consecutive HCV RNA negative
      assessment, incidence of reinfection was 31/100 person-years (95% CI, 17-62/100
      person-years). Following adjustment for HCV risk behaviour variables the
      incidence rate ratio of HCV reinfection to initial infection was 1.11 (P = 0.8).
      Several cases of HCV reinfection appear to have developed persistent infection.

PMID- 17501763
TI  - No significant differences in histology and response to interferon treatment in
      hepatitis B carriers of genotypes C and recombinant B.
AB  - Hepatitis B virus (HBV) genotypes B and C are most prevalent in China and
      genotype B is found exclusively in recombination with the pre-C/C gene of
      genotype C. We investigated whether there is a difference in clinical relevance
      between the two genotypes sharing the same pre-C/C gene. Thus, we determined the
      genotype of HBV among consecutive HBeAg-positive patients with tailored
      interferon-alpha (IFN-alpha) therapy, and the demographic, baseline clinical
      characteristics and treatment results were compared between them. The median
      values of alanine transaminase (ALT) were 4.5 and 5.0 times the upper limit of
      normal (P = 0.419), HBV-DNA levels were 1.4 x 10(7) and 1.5 x 10(7)copies/mL (P =
      0.829), mean scores of necroinflammatory histological activity 9.8 and 10.44 (P =
      0.105) and fibrotic activity 2.64 and 2.86 (P = 0.227) in genotype B and C
      patients, respectively. The end-of-treatment response was 42.7% and 39.0% (P =
      0.531) with mean tailored treatment months of 8.28 and 9.34 (P = 0.160), and the
      sustained response 43.4% and 37.5% (P = 0.31) at the end of a 12-month follow-up
      period in genotype B and C patients, respectively. These results remained similar
      when follow-up was extended to nearly 3 years. In conclusion, no significant
      differences in clinical characteristics and response to IFN-alpha between
      genotypes B and C were found, probably, because both types shared a common pre
      C/C encoding region.

PMID- 17501764
TI  - Distribution and characteristics of hepatitis B virus genotype C subgenotypes in
      China.
AB  - Genetic diversity within the same hepatitis B virus (HBV) genotype indicates the
      presence of several subgenotypes. We have found that genotype C is the most
      common in China, and this study aimed to determine the geographical distribution
      and characteristics of HBV-C subgenotypes in the country. A cohort of 534
      patients with chronic HBV genotype C infection, collected across China, was
      analysed by nucleotide sequencing or polymerase chain reaction-restriction
      fragment length polymorphism. HBV-C1/Cs (n = 112, 21%) and HBV-C2/Ce (n = 397,
      74%) were the most common HBV-C subgenotypes and showed different geographical
      distribution in China. No significant differences were found between patients
      infected with HBV-C1 and HBV-C2 when comparing liver function tests, hepatitis B
      e antigen positive rate and clinical manifestations. We identified two other
      types of HBV-C provisionally designated as HBV-CD1 and HBV-CD2, which have
      particular virological features and clustered in one geographic area. These two
      types of C/D hybrids have emerged through recombination with genotype D and
      encode serotype ayw2 hepatitis B surface antigen. In conclusion, there are at
      least four subtypes of HBV genotype C: subgenotypes C1, C2 and two types of C/D
      recombinants CD1 and CD2 in China, which have a distinct geographic distribution.
      Whether HBV-C subgenotypes differ in their impact on liver disease progression
      requires prospective studies.

PMID- 17501765
TI  - Evaluation of human (genotype 1) and swine (genotype 4)-ORF2-based ELISAs for
      anti-HEV IgM and IgG detection in an endemic country and search for type 4 human
      HEV infections.
AB  - Open reading frame 2 proteins (ORF2) from swine (genotype 4, S-ORF2) and human
      (genotype 1, H-ORF2) hepatitis E virus (HEV) having 91.4% identity at amino acid
      level were expressed using baculovirus expression system. Comparison of ELISAs
      based on the two proteins yielded identical results when sequential serum samples
      from monkeys and pigs experimentally infected with genotypes 1 and 4 HEV,
      respectively, were tested. Samples from patients (n = 258) suffering from non-A,
      non-B hepatitis during outbreaks of the disease and 180 sera from apparently
      healthy children were screened by H-ORF2-, S-ORF2-based ELISAs and Genelabs
      ELISA, a widely used commercial test for HEV diagnosis. Specificity of all three
      tests in detecting IgM and IgG antibodies in healthy children was comparable.
      Excellent correlation was noted in detecting both IgM (98.7% concordance) and IgG
      (97.7% concordance) anti-HEV antibodies when H-ORF2 and S-ORF2 ELISAs were
      compared. When compared with Genelabs ELISA, both H-ORF2 and S-ORF2 ELISAs
      identified 34 and 18 additional positives, respectively, in IgM and IgG anti-HEV
      tests showing comparatively less sensitivity of the commercial assay. The
      concordance of Genelabs ELISA in IgM detection was 86.4% and 85.6%, respectively,
      with H-ORF2 and S-ORF2 ELISAs. The concordance between Genelabs ELISA and H-ORF2
      decreased further to 73.6% when 129 human samples from recent HEV epidemics (2002
      2004) were tested for IgM. Similar results were obtained when sequential samples
      from 11 hepatitis E patients were examined. Screening of serum samples from 137
      sporadic non-A, non-B hepatitis cases further confirmed the superiority of the H
      ORF2 and S-ORF2 ELISAs. All 36/137 HEV-RNA-positive samples from sporadic cases
      belonged to genotype 1 confirming absence/rarity of type 4 human infections. H
      ORF2 and S-ORF2 antigens were swappable in ELISAs for detecting both genotypes 1
      and 4 HEV infections.

PMID- 17501766
TI  - Variations in cervical IL-10 and IL-8 concentrations throughout gestation in
      normal pregnancies.
AB  - PROBLEM: Data regarding cervical interleukin 18 (IL-8) and IL-10 concentrations
      during pregnancy is limited. METHOD OF STUDY: This was a cross sectional study of
      healthy pregnant women. Specimens were collected from the cervical os secretions.
      IL-8 and IL-10 levels were measured by using enzyme-linked immunosorbent assay.
      Median (range) cytokine concentrations were derived for each trimester and
      compared across trimesters. The relationship between gestational age and cytokine
      levels was assessed by regression analysis. The mean of the ratios of IL-8 to IL
      10 was compared in each trimester using anova. RESULTS: The median (range) IL-8
      concentrations in cervical secretions were in pg/mL: 1562 (1210-4100), 2460 (1047
      4688), 3660 (1451-4748) (P < 0.0021); the median (range) IL-10 concentrations in
      cervical secretions were in pg/mL: 38.3 (6.8-227.9), 10.9 (0-263.3), 9.5 (0
      35.6); the mean IL10/IL-8 x 100 (+/- standard deviation) concentrations were:
      3.33 +/- 0.65, 1.47 +/- 0.41, 0.38 +/- 0.52 (P = 0.0035) during the first, second
      and third trimesters, respectively. CONCLUSION: The patterns of cervical IL-8
      concentration is inversely related to gestational age, and the ratio of IL-10/IL
      8 decreases with advancing gestation.

PMID- 17501767
TI  - Elevation of amniotic fluid macrophage colony-stimulating factor in normotensive
      pregnancies that delivered small-for-gestational-age infants.
AB  - PROBLEM: Macrophage colony-stimulating factor (M-CSF) promotes placental growth
      and maintenance. We evaluated whether amniotic fluid M-CSF levels were altered in
      normotensive pregnancies that produced small-for-gestational-age (SGA) infants
      arising from unknown factors. METHOD OF STUDY: This study enrolled 68 Japanese
      women experiencing normotensive pregnancies with single fetuses. Of these
      pregnancies, 22 delivered SGA infants arising from unknown factors (SGA group);
      one delivered an SGA infant with intestinal obstruction. The other 45 were women
      who delivered appropriate-for-gestational-age (AGA) infants (AGA group). They
      were selected as controls. Amniotic fluid was collected and the M-CSF levels were
      compared between the two groups. The M-CSF level was determined by enzyme-linked
      immunosorbent assay method. RESULTS: Amniotic fluid M-CSF concentrations were
      6525 pg/mL (median) in the SGA group and 4790 pg/mL in the AGA group; the
      concentrations were significantly higher in the SGA group than in the AGA group.
      The M-CSF concentrations in the woman who delivered an SGA infant with intestinal
      obstruction showed very high values (24290 pg/mL). CONCLUSION: We demonstrated a
      significant increase in amniotic fluid M-CSF levels in the SGA group. Excessive
      concentrations of M-CSF in amniotic fluid via amniotic membranes may be highly
      related to immunological abnormalities contributing to low birth weight of
      neonates.

PMID- 17501845
TI  - Can migraineurs accurately identify their headaches as "migraine" at attack
      onset?
AB  - BACKGROUND: While treating migraine early when the headache is mild is believed
      to link to improved treatment outcomes, it is not clear whether patients can
      correctly self-identify a headache as a migraine at onset in real-world settings.
      OBJECTIVE: This study aims to assess the likelihood that patients can correctly
      self-identify a headache as a migraine at onset, and to evaluate cues that
      patients use to correctly identify migraine attacks. METHODS: Adult migraineurs
      were recruited from 14 headache clinics across the United States. Patients
      recorded their headache experiences via an electronic diary daily over a period
      of 30 days. On days when they experienced headaches, patients were asked to
      recall the types of headache they experienced at both onset and peak. Patients
      also identified cues for deciding whether the headache was a migraine or not.
      Using identification of migraine at headache peak as the criterion, we examined
      the sensitivity and specificity of migraine identification at onset. We employed
      generalized estimating equation (GEE) to evaluate factors identified at headache
      onset that predicted migraine identified at headache peak. RESULTS: Of the 192
      enrolled patients, 182 patients recorded a total of 1197 headache episodes over
      30 days. At headache onset, 888 episodes were deemed by patients as migraine and
      309 episodes not migraine; a majority (92%) of these early migraine
      identifications were confirmed at headache peak. Sensitivity and specificity of
      self-identification of migraine at onset were 91% and 97%, respectively. A number
      of factors at headache onset were predictive of a migraine identified at peak:
      sensitivity to light (OR = 3.1, 95% CI: 1.9-5.0), headache severity (OR = 2.0,
      95% CI: 1.4-2.8), nausea symptoms (OR = 2.6, 95% CI: 1.5-4.5), and visual
      disturbance (OR = 2.3, 95% CI: 1.1-4.9). Patients who ruled out tension-type
      headache at onset were twice (OR = 2.0, 95% CI: 1.5-2.8) as likely to conclude a
      migraine at peak. CONCLUSIONS: Most migraineurs in tertiary care settings can
      correctly self-identify a headache as a migraine at onset. Factors such as
      headache severity, presence of nausea, visual disturbance, sensitivity to light,
      and no tension-type headache, appeared to augment the correct identification.

PMID- 17501846
TI  - Effectiveness of yoga therapy in the treatment of migraine without aura: a
      randomized controlled trial.
AB  - BACKGROUND: Numerous studies have explored the effectiveness of complementary and
      alternative medicine in the treatment of migraine but there is no documented
      investigation of the effectiveness of yoga therapy for migraine management.
      OBJECTIVES: To investigate the effectiveness of holistic approach of yoga therapy
      for migraine treatment compared to self-care. DESIGN: A randomized controlled
      trial. METHODS: Seventy-two patients with migraine without aura were randomly
      assigned to yoga therapy or self-care group for 3 months. Primary outcomes were
      headache frequency (headache diary), severity of migraine (0-10 numerical scale)
      and pain component (McGill pain questionnaire). Secondary outcomes were anxiety
      and depression (Hospital anxiety depression scale), medication score. RESULTS:
      After adjustment for baseline values, the subjects' complaints related to
      headache intensity (P < .001), frequency (P < .001), pain rating index (P <
      .001), affective pain rating index (P < .001), total pain rating index (P <
      .001), anxiety and depression scores (P < .001), symptomatic medication use (P <
      .001) were significantly lower in the yoga group compared to the self-care group.
      CONCLUSION: The study demonstrated a significant reduction in migraine headache
      frequency and associated clinical features, in patients treated with yoga over a
      period of 3 months. Further study of this therapeutic intervention appears to be
      warranted.

PMID- 17501847
TI  - Myofascial trigger points, neck mobility, and forward head posture in episodic
      tension-type headache.
AB  - OBJECTIVE: To assess the differences in the presence of trigger points (TrPs) in
      head and neck muscles, forward head posture (FHP) and neck mobility between
      episodic tension-type headache (ETTH) subjects and healthy controls. In addition,
      we assess the relationship between these muscle TrPs, FHP, neck mobility, and
      several clinical variables concerning the intensity and the temporal profile of
      headache. BACKGROUND: TTH is a headache in which musculoskeletal disorders of the
      craniocervical region might play an important role in its pathogenesis. Design.-A
      blinded, controlled pilot study. METHODS: Fifteen ETTH subjects and 15 matched
      controls without headache were studied. TrPs in both upper trapezius, both
      sternocleidomastoids, and both temporalis muscles were identified according to
      Simons and Gerwin diagnostic criteria (tenderness in a hypersensible spot within
      a palpable taut band, local twitch response elicited by snapping palpation, and
      elicited referred pain with palpation). Side-view pictures of each subject were
      taken in both sitting and standing positions, in order to assess FHP by measuring
      the craniovertebral angle. A cervical goniometer was employed to measure neck
      mobility. All measures were taken by a blinded assessor. A headache diary was
      kept for 4 weeks in order to assess headache intensity, frequency, and duration.
      RESULTS: The mean number of TrPs for each ETTH subject was 3.7 (SD: 1.3), of
      which 1.9 (SD: 0.9) were active, and 1.8 (SD: 0.9) were latent. Control subjects
      only had latent TrPs (mean: 1.5; SD: 1). TrP occurrence between the 2 groups was
      significantly different for active TrPs (P < .001), but not for latent TrPs (P >
      .05). Differences in the distribution of TrPs were significant for the right
      upper trapezius muscles (P= .04), the left sternocleidomastoid (P= .03), and both
      temporalis muscles (P < .001). Within the ETTH group, headache intensity,
      frequency, and duration outcomes did not differ depending on TrP activity,
      whether the TrP was active or latent. The craniovertebral angle was smaller, ie,
      there was a greater FHP, in ETTH patients than in healthy controls for both
      sitting and standing positions (P < .05). ETTH subjects with active TrPs in the
      analyzed muscles had a greater FHP than those with latent TrPs in both sitting
      and standing positions, though differences were only significant for certain
      muscles. Finally, ETTH patients also showed lesser neck mobility than healthy
      controls in the total range of motion as well as in half-cycles (except for
      cervical extension), although neck mobility did not seem to influence headache
      parameters. CONCLUSIONS: Active TrPs in the upper trapezius, sternocleidomastoid,
      and temporalis muscles were more common in ETTH subjects than in healthy
      controls, although TrP activity was not related to any clinical variable
      concerning the intensity and the temporal profile of headache. ETTH patients
      showed greater FHP and lesser neck mobility than healthy controls, although both
      disorders were not correlated with headache parameters.

PMID- 17501848
TI  - Efficacy of eletriptan in migraine-related functional impairment: functional and
      work productivity outcomes.
AB  - OBJECTIVE: To provide a multidimensional assessment of the extent of functional
      impairment during an acute migraine attack, and of the improvement in functioning
      in response to treatment, using 4 concurrently administered scales: the 7-item
      work productivity questionnaire (PQ-7), the functional assessment in migraine
      (FAIM) activities and participation (FAIM-A&P) subscale, the FAIM-impact of
      migraine on mental functioning (FAIM-IMMF) subscale, and the traditional 4-point
      global functional impairment scale (FIS). METHODS: Outpatients with an
      International Classification of Headache Disorders diagnosis of migraine were
      randomized to double-blind treatment of a single attack with either oral
      eletriptan 20 mg (n = 192) once-daily, eletriptan 40 mg (N = 213) once-daily, or
      placebo (n = 208). Patients were encouraged to take study medication as soon as
      they were sure they were experiencing a typical migraine headache, after the aura
      phase (if present) had ended. Patients with moderate-to-severe functional
      impairment were identified on each of the 4 disability scales, and 2-hour
      functional response was compared between treatments. RESULTS: At baseline, the PQ
      7 and FAIM-IMMF items that assessed ability to perform tasks requiring
      concentration, sustained work or attention, and ability to think quickly or
      spontaneously, were especially sensitive to the effects of mild headache pain,
      with 27% to 48% of patients (n = 92-112) reporting moderate-to-severe impairment.
      Only 11.3% of patients (n = 112) reported this level of impairment due to mild
      pain on the FIS. Functional response at 2 hours was significantly higher on
      eletriptan 40 mg versus placebo on the FAIM-A&P (63% vs 36%; n = 218; P < .0001);
      on the PQ-7 (56% vs 34%; n = 116; P= .0052); and on the FAIM-IMMF (50% vs 34%; n
      = 215; P= .017). These rates were all lower than the functional response rates on
      the FIS for eletriptan 40 mg (75%) and eletriptan 20 mg (70%) versus placebo
      (45%; P < .001). Conclusions.-In this exploratory analysis, use of
      multidimensional scales was found to provide a sensitive measure of headache
      related functional impairment, especially for detecting clinically meaningful
      cognitive effects, and for detecting drug versus placebo differences.

PMID- 17501849
TI  - Sumatriptan/Naproxen sodium for migraine: efficacy, health related quality of
      life, and satisfaction outcomes.
AB  - OBJECTIVE: To describe the pain relief, satisfaction, and health-related quality
      of life results of moderate or severe migraines treated with a
      sumatriptan/naproxen sodium combination tablet. METHODS: Sumatriptan and naproxen
      sodium as a single-dose formulation tablet was used to treat moderate to severe
      migraines over a 12-month period in a phase 3, open-label, multicenter study (n =
      565) in patients with at least 6 months' history of migraine headaches. RESULTS:
      Seventy percent of all attacks were treated with 1 dose of sumatriptan/naproxen
      sodium. Overall subjects treated 24,485 attacks; of these, 81% attacks achieved
      pain relief and 60% pain-free by 2 hours. At 3 months, the percentage of patients
      satisfied or very satisfied increased from baseline on all 8 Patient Perception
      of Migraine Questionnaire (PPMQ) items and remained high throughout the study.
      Mean Migraine-Specific Quality of Life Questionnaire (MSQ) domain scores also
      increased by 13-15 points from baseline during this time and remained high.
      CONCLUSIONS: Sumatriptan/naproxen sodium provides consistent relief of migraine
      attacks over 12 months, resulting in improved patient satisfaction and migraine
      specific quality of life.

PMID- 17501850
TI  - Improvement of chronic headache after treatment of unruptured intracranial
      aneurysms.
AB  - OBJECTIVE: The objective of this study is to determine the incidence, character,
      and outcome of headache in patients with unruptured intracranial aneurysms who
      had been treated to avoid the risk of rupture. BACKGROUND: There are a variety of
      clinical manifestations associated with unruptured intracranial aneurysms. Among
      them, chronic headache is the most common presenting and/or accompanying symptom.
      METHODS: Among the 137 patients with unruptured aneurysms who had been treated,
      we collected 81 patients excluding 30 on the basis of inclusion criteria. Twenty
      six patients were lost to follow-up. We collected data by medical record review
      and a telephone survey. Included in the information collected was the analysis of
      presenting symptom, location and size of each aneurysm, location, quality,
      intensity and duration of headaches, associated symptoms, triggering and
      alleviating factors, and precipitating events. RESULTS: Forty-nine patients
      (60.5%) of 81 had chronic headaches before the diagnosis of unruptured
      intracranial aneurysm. Forty-four patients (89.8%) answered that their headaches
      were improved slightly (12 patients) or markedly (32 patients) (P <.05). The
      clinical pattern of the headache worsened in only 1 patient and did not change in
      4 patients. When the surgical group (40 patients) and the coil embolization group
      (41 patients) were compared, there was no significant difference observed in
      outcome (P >.05). CONCLUSION: Either by employing the technique of clipping or by
      coil embolization, treatment of unruptured intracranial aneurysms resulted in
      relief of headaches in majority of patients who had headaches pre-operatively.

PMID- 17501851
TI  - Mmp-9 immunoreactivity in acute migraine.
AB  - OBJECTIVE: To examine the role of matrix metalloproteinase 9 (MMP-9) in migraine
      during headache and asymptomatic periods. METHODS: Thirty-four patients with
      migraine with and without aura (according to International Headache Society
      criteria) were studied. Clinical characteristic of headache were recorded. Blood
      samples for measurement of MMP-9 were drawn during headache attacks and during
      asymptomatic periods in all patients and in 10 healthy controls. RESULTS: We
      found higher plasma MMP-9 levels in migraine patients than in control group
      (129.3 [78.0-258.9] vs. 49.6 [39.1-64.3] ng/mL; P < .001). Migrainous patients
      showed higher MMP-9 plasma levels during headache attacks than in asymptomatic
      periods, both in migraine without aura (338.4 [275.1-396.2] vs. 118.2 [75.3
      137.5] ng/mL; P < .0001), and migraine with aura (389.3 [273.4-487.1] vs. 139.3
      [107.3-191.4] ng/mL; P < .0001). CONCLUSIONS: Our study showed an increased
      production of MMP-9 during migraine attacks. These data suggest a possible role
      of inflammation or blood-brain barrier disruption during the migraine attack.

PMID- 17501852
TI  - Emergency department management of acute migraine in children in Canada: a
      practice variation study.
AB  - OBJECTIVES: Evidence-based guidelines for the treatment of children with migraine
      are limited given the paucity of randomized controlled trials, especially in the
      emergency department (ED). Our objectives were to: (1) characterize the treatment
      of children with migraine in the ED; (2) determine whether treatment varies in
      pediatric versus mixed (pediatric and adult) EDs. METHODS: Children aged 5 to 17
      years presenting to 4 regional emergency departments in Edmonton, Alberta, Canada
      during the 2003/2004 fiscal year with a diagnostic code of headache or migraine
      were selected. A standardized retrospective chart abstraction was performed and
      migraine or probable migraine cases were classified based on the International
      Classification of Headache Disorders II. RESULTS: Three hundred and eighty-two
      cases were identified of which 48.7% (n = 186/382) met sufficient criteria for
      migraine. No treatment was given in 44.2% (n = 169/382). Simple oral analgesics
      (23.3%; n = 89/182) and dopamine antagonists (metoclopramide and
      prochlorperazine; 20.7%; n = 79/182) were prescribed first-line most commonly.
      Opiate medications (5.5%), ketorolac (4.7%), dihydroergotamine (1%) were
      prescribed first-line infrequently. There was a significant difference in the
      management choices between pediatric and mixed adult/pediatric EDs (chi(2)=
      19.695; df = 5; P= .001). The pediatric ED was more likely to prescribe a
      dopamine antagonist (12.9 vs 6.8%; P= .044) while the mixed adult/pediatric EDs
      were more likely to prescribe an opiate (28.1% vs 18.4%; P= .031). Children with
      migraine in all EDs were significantly more likely to receive drug therapy (68.3%
      vs 42.9%; P < .001) or a dopamine antagonist (32.3% vs 9.7%; P < .001).
      Polypharmacy (31.2%; n = 119/382) and neuroimaging (29.1%; n = 111/382) were
      common. Outcome was poorly documented overall. No adverse events were recorded.
      CONCLUSIONS: Significant variation in practice in the management of acute
      headaches in children was observed between mixed population and pediatric-only
      emergency physicians in the same city. Most children do not receive any drug
      therapy. Children presenting to the pediatric ED were significantly more likely
      to receive a dopamine antagonist while opiates were prescribed more commonly in
      the mixed ED. More clinical trials are required in children to clarify areas of
      clinical uncertainty on which evidence-based practice guidelines can be formed.

PMID- 17501853
TI  - The phe-124-Cys and A-161T variants of the human 5-HT1B receptor gene are not
      major determinants of the clinical response to sumatriptan.
AB  - BACKGROUND: The 5-HT(1B/1D) receptor agonist sumatriptan is highly effective in
      the treatment of migraine. However, some patients do not respond to sumatriptan
      or experience recurrence of the headache after initial relief. In addition, some
      patients report chest symptoms after the use of sumatriptan. OBJECTIVE: To assess
      whether 2 genetic variants (F124C changing a phenylalanine for a cysteine and
      polymorphism A/T at nucleotide position -161 in the 5' regulatory region) of the
      5-HT(1B) receptor play a major role in the therapeutic response to sumatriptan.
      The 5-HT(1B) receptor most likely mediates the therapeutic action and coronary
      side effects of sumatriptan, and both F124C and A-161T have relevant functional
      consequences on either the affinity of sumatriptan to bind to the 5-HT(1B)
      receptor or on receptor expression level itself, respectively. METHOD: Genomic
      DNA of a relatively small but very well-characterized set of migraine patients
      with consistently good response to sumatriptan (n = 14), with no response (n =
      12), with recurrence of the headache (n = 12), with chest symptoms (n = 13), and
      patients without chest symptoms (n = 27) was available for the genetic analyses
      and screened for the F124C variant and the A-161T polymorphism in the human 5
      HT(1B) receptor gene. RESULTS: F124C was not detected in any of the patients
      studied. In addition, we did not observe drastic changes in allele frequencies of
      the A-161T polymorphism that might hint to a causal relation with the therapeutic
      effect of sumatriptan. CONCLUSION: We have not obtained any evidence that
      variants F124C and A-161T of the 5-HT(1B) receptor are major determinants in the
      clinical response to sumatriptan.

PMID- 17501854
TI  - Neurocysticercosis.

PMID- 17501855
TI  - Airplane descent headaches.

PMID- 17501856
TI  - Thunderclap headache as the presenting symptom of myocardial infarction.
AB  - Headache as the presenting symptom of myocardial ischemia has been reported in
      more than 20 cases. These headaches have been described as of gradual onset,
      associated with exertion and with EKG changes. We present herein the first case
      of thunderclap headache occurring at rest as the sole symptom of an acute
      myocardial infarction.

PMID- 17501857
TI  - Ophthalmoplegic migraine with alternating unilateral and bilateral internal
      ophthalmoplegia.
AB  - We describe a patient with ophthalmoplegic migraine and internal ophthalmoplegia
      with alternating unilateral involvement and bilateral involvement in whom brain
      MRI scan showed alternating gadolinium enhancement on the cisternal portion of
      the oculomotor nerve.

PMID- 17501858
TI  - Sympathetic nerve blocks in mandibular herpes zoster and postherpetic neuralgia.
AB  - Sympathetic blocks have been indicated for the diagnosis and treatment of painful
      neuropathic conditions, such as herpes zoster (HZ) and postherpetic neuralgia
      (PHN). The purpose of this article is to report a case of mandibular HZ and PHN
      in an HIV-positive patient, and discuss the efficacy of sympathetic nerve blocks
      for pain relief and prevention of PHN.

PMID- 17501859
TI  - Successful treatment of postcraniectomy orthostatic headache with lumbar epidural
      blood patches.
AB  - Postcraniectomy orthostatic headache is a rare, but disabling, condition which
      can often interfere with patient rehabilitation. Previously, postsurgical CSF
      leaks have generally been managed with surgical repair. We present the case of a
      32-year-old man with postcraniectomy orthostatic headache which was successively
      managed with repeated lumbar epidural blood patches.

PMID- 17501861
TI  - Teaching case: hemicranial headaches.

PMID- 17501862
TI  - Patient information regarding subcutaneous self-administration of
      dihydroergotamine (DHE).

PMID- 17501864
TI  - The ethics of the use of technologically constructed high-altitude environments
      to enhance performances in sport.

PMID- 17501865
TI  - Injuries among judokas during competition.
AB  - AIMS: To investigate the type and severity of injury sustained during judo
      competitions, and to investigate any possible correlation between injury rate and
      gender, grade, weight category and rapid weight loss. METHOD: Three hundred and
      ninety-two judokas (284 males, 108 females) competed in three consecutive
      competitions. A judoka was "injured" if they requested medical treatment or could
      not continue. Following injury, a questionnaire was completed. Uninjured judokas
      were asked to complete a questionnaire at one competition to assess risk factors
      of injury. Follow-up was conducted 6 weeks after each competition. RESULTS: Fifty
      three out of 392 judokas (13.5%) (40 males, 13 females) sustained an injury. No
      difference was found between injury rates among males (41.3/1000 anthlete
      exposures (A-E's)) and females (40.9/1000 A-E's), or between judokas of different
      weight groups or grades. Rapid weight loss of 5% or more of a judoka's body
      weight placed the athlete at a higher risk of injury (P=0.022). Most injuries
      affected the upper extremities. Injuries most often resulted from grip fighting,
      being thrown, or attempting to throw. CONCLUSIONS: Judokas are advised not to
      lose weight before a competition as this increases the risk of injury. Neither
      grade, nor gender, or weight category are associated with an increase in injury
      rate.

PMID- 17501866
TI  - Long-term results after primary repair or non-surgical treatment of anterior
      cruciate ligament rupture: a randomized study with a 15-year follow-up.
AB  - We investigated the long-term outcome of 100 patients 15 years after having been
      randomly allocated to primary repair (augmented or non-augmented) or non-surgical
      treatment of an anterior cruciate ligament (ACL) rupture. The subjective outcome
      was similar between the groups, with no difference regarding activity level and
      knee-injury and osteoarthritis outcome score but with a slightly lower Lysholm
      score for the non-surgically treated group. This difference was attributed to
      more instability symptoms. The radiological osteoarthritis (OA) frequency did not
      differ between surgically or non-surgically treated patients, but if a
      meniscectomy was performed, two-thirds of the patients showed OA changes
      regardless of initial treatment of the ACL. There were significantly more
      meniscus injuries in patients initially treated non-surgically. One-third of the
      patients in the non-surgically treated group underwent secondary ACL
      reconstruction due to instability problems. In this study, ACL repair itself
      could not reduce the risk of OA nor increase the subjective outcome scores.
      However, one-third of the non-surgical treated patients were later ACL
      reconstructed due to instability. The status of the menisci was found to be the
      most important predictor of developing OA. Early ACL repair and also ACL
      reconstruction can reduce the risk of secondary meniscus tears. Indirectly this
      supports the hypothesis that early stabilization of the knee after ACL injury is
      advantageous for the long-term outcome.

PMID- 17501867
TI  - Secular trends of physical fitness in Swedish adults.
AB  - The aim of the present study was to study differences in fitness (maximal aerobic
      power (VO(2max)), balance control, abdominal strength and endurance) and
      anthropometric data in Swedish women and men (20-65 years of age) between two
      national cross-sectional samples, studied in 1990/1991 and 2000/2001,
      respectively. The absolute and relative VO(2max) (aerobic fitness), estimated
      from a submaximal test, declined with increasing age in both genders. The
      submaximal test was validated against running VO(2max). Furthermore, the relative
      aerobic fitness (mL/min/kg) was lower in the 2000/2001 sample in men but not in
      women. Overall physical activity level was unchanged in both genders. An
      unexpected finding was that in both samples there were no major differences in
      relative VO(2max) between men and women of the same age. Combined overweight and
      obesity (body mass index> or =25) is becoming more prevalent in men, but not in
      women with prevalence in 2000/2001 of 61% and 38% for men and women,
      respectively. Balance control and abdominal strength and endurance decrease with
      increasing age with no differences between the two samples. Thus, the near future
      health situation for men may be worse, while for women it may be less or no
      differences compared with today.

PMID- 17501868
TI  - Genetic effects in common on maximal walking speed and muscle performance in
      older women.
AB  - The purpose was to examine whether maximal walking speed, maximal isometric knee
      extensor strength, and leg extensor power share genetic or environmental effects
      in common. The data was collected from 103 monozygotic and 114 dizygotic female
      twin pairs aged 63-76 years. Maximal walking speed over 10 m was measured in the
      laboratory corridor using photocells for timing. Isometric knee extensor strength
      and leg extensor power were measured using an adjustable dynamometer. The genetic
      models showed that strength, power, and walking speed had a genetic effect in
      common which accounted for 52% of the variance in strength, 36% in power, and 34%
      in walking speed. Strength and power had a non-shared environmental effect in
      common explaining 13% of variation in strength and 14% in power. The remaining
      variance was accounted for by trait-specific effects. Some people may be more
      prone to functional limitation in old age due to their genetic disposition, but
      this does not rule out that changes in the lifestyle of predisposed subjects may
      also have a major effect. Approximately half of the variation in each trait was
      explained by environmental effects, which suggests the importance of the physical
      activity to improve performance and prevent functional limitation.

PMID- 17501869
TI  - Exercise economy does not change after acclimatization to moderate to very high
      altitude.
AB  - For more than 60 years, muscle mechanical efficiency has been thought to remain
      unchanged with acclimatization to high altitude. However, recent work has
      suggested that muscle mechanical efficiency may in fact be improved upon return
      from prolonged exposure to high altitude. The purpose of the present work is to
      resolve this apparent conflict in the literature. In a collaboration between four
      research centers, we have included data from independent high-altitude studies
      performed at varying altitudes and including a total of 153 subjects ranging from
      sea-level (SL) residents to high-altitude natives, and from sedentary to world
      class athletes. In study A (n=109), living for 20-22 h/day at 2500 m combined
      with training between 1250 and 2800 m caused no differences in running economy at
      fixed speeds despite low typical error measurements. In study B, SL residents
      (n=8) sojourning for 8 weeks at 4100 m and residents native to this altitude
      (n=7) performed cycle ergometer exercise in ambient air and in acute normoxia.
      Muscle oxygen uptake and mechanical efficiency were unchanged between SL and
      acclimatization and between the two groups. In study C (n=20), during 21 days of
      exposure to 4300 m altitude, no changes in systemic or leg VO(2) were found
      during cycle ergometer exercise. However, at the substantially higher altitude of
      5260 m decreases in submaximal VO(2) were found in nine subjects with acute
      hypoxic exposure, as well as after 9 weeks of acclimatization. As VO(2) was
      already reduced in acute hypoxia this suggests, at least in this condition, that
      the reduction is not related to anatomical or physiological adaptations to high
      altitude but to oxygen lack because of severe hypoxia altering substrate
      utilization. In conclusion, results from several, independent investigations
      indicate that exercise economy remains unchanged after acclimatization to high
      altitude.

PMID- 17501870
TI  - The Swedish Blood Pass project.
AB  - Manipulation of the blood's oxygen carrying capacity (CaO(2)) through reinfusion
      of red blood cells, injections of recombinant erythropoietin or by other means
      results in an increased maximal oxygen uptake and concomitantly enhanced
      endurance performance. Therefore, there is a need to establish a system--"A Blood
      Pass"--through which such illegal and unethical methods can be detected. Venous
      blood samples were taken under standardized conditions from 47 male and female
      Swedish national and international elite endurance athletes four times during the
      athletic year of the individual sport (beginning and end of the preparation
      period and at the beginning and during peak performance in the competition
      period). In these samples, different hematological values were determined.
      ON(hes) and OFF(hre) values were calculated according to the formula of Gore et
      al. A questionnaire regarding training at altitude, alcohol use and other
      important factors for hematological status was answered by the athletes. There
      were some individual variations comparing hematological values obtained at
      different times of the athletic year or at the same time in the athletic year but
      in different years. However, the median values of all individual hematological,
      ON(hes) and OFF(hre), values taken at the beginning and the end of the
      preparation or at the beginning and the end of the competition period,
      respectively, as well as median values for the preparation and competition
      periods in the respective sport, were all within the 95% confidence limit (CI) of
      each comparison. It must be mentioned that there was no gender difference in this
      respect. This study shows that even if there are some individual variations in
      different hematological values between different sampling times in the athletic
      year, median values of important hematological factors are stable over time. It
      must be emphasized that for each blood sample, the 95% CI in each athlete will be
      increasingly narrower. The conclusion is that there is a physiological basis for
      establishing an individual-based "Blood Pass" system, mainly for athletes
      competing at the international level. On indications of manipulations of
      hemoglobin concentration and red cell mass by deviations from established "Blood
      Pass" data, more specific methods can be applied.

PMID- 17501871
TI  - Eccentric rehabilitation exercise increases peritendinous type I collagen
      synthesis in humans with Achilles tendinosis.

PMID- 17501873
TI  - Periprosthetic femoral fractures: a growing but potentially avoidable problem?

PMID- 17501874
TI  - Supplementary oxygen and wound healing in vascular surgery: too simple to be
      true?

PMID- 17501875
TI  - Routine prevention of venous thromboembolism after surgery: the time for action.

PMID- 17501876
TI  - Cancer stem cells in 2007.

PMID- 17501877
TI  - Looking both ways: the Jamieson Memorial Lecture, 2006.
AB  - The Jamieson Memorial Lecture, delivered annually to the Neurosurgical Society of
      Australasia, commemorates the life and work of a leading Australasian
      neurosurgeon, Dr Kenneth Grant Jamieson (1925-1976), of Melbourne and Brisbane.
      He was the first specialist neurosurgeon to be appointed to the Brisbane General
      Hospital, the Brisbane Children's Hospital and the newly established Princess
      Alexandra Hospital in Queensland, jointly in 1956. He went on to serve as
      President of the Neurosurgical Society of Australasia (1971-1973) and as a
      Councillor of the Royal Australasian College of Surgeons from 1971 until his
      death. His pioneering research to study the sociophysical interplay of factors
      leading not only to head and spinal injury but to those causing all life
      threatening trauma gave weight (from 1961) to advocacy for the introduction of
      breathalyser surveillance and to the compulsory wearing of seat belts in cars. In
      international perspective, Kenneth Jamieson was a pioneering 'accidentologist'.
      He was one of the first clinicians to address seriously the extraordinary burden
      of mortality from road trauma. He was a role model for those clinicians who came
      to see their professional and ethical duties extending to preventive and public
      health domains, both within and beyond the aegis of their chosen specialties. He
      saw a need for integration between the many bodies teaching resuscitation and
      life-support skills; at the 1975 Annual Scientific Meeting of the Royal
      Australasian College of Surgeons, he moved the motion to establish the Australian
      Resuscitation Council. The vigour and outreach of the Australian Resuscitation
      Council today remain one of his memorials. In the clinical sphere, his research
      centred on the early drainage of extradural haematomata and from 1962 on the
      operative treatment of aneurysms of the vertebral and basilar arteries. He was a
      dominant and leading advocate for clinical teaching in neurosurgery, particularly
      for more formal and sophisticated clinical teaching, improved training and higher
      standards of neurosurgical nursing. In a humorous but profound after-dinner
      speech, delivered to the Neurosurgical Society of Australasia (NSA) in 1973,
      Kenneth Jamieson acknowledged the 'importance of hindsight' as a desirable
      attribute for all neurosurgeons. The 2006 Jamieson Memorial Lecture takes this
      theme, extending it by using the metonymic symbolism of the NSA, whose emblem
      features two lizards, vertebrates with prominent postpineal midline parietal
      eyes. 'Looking both ways' stresses the desirability of all doctors to develop
      their knowledge of the history of their specialty in order that perspective might
      be enhanced. In this theme of 'looking back', the author draws particularly upon
      the contributions of three other Australians in the progression of neurosurgery:
      Lord Florey, Brigadier Sir Hugh Cairns and Dr Dorothy Russell. In 'looking
      forward', the author gives several examples of futurists who have striven to
      advance the causes not only of neurosurgery but of other cognate medical
      disciplines. Effective futurists are those who do not simply prognosticate, but
      combine prophecy with a will to modify the future, and who in so doing hold
      optimistic views for the future. Such an approach needs special attributes if
      pioneering advocacy for improvement is to be both directed and ultimately
      successful. The attributes needed to be a medical historian-futurist are
      summarized in the themes of (i) perspective; (ii) courageous resilience and
      optimism; (iii) evangelistic enthusiasm; and (iv) the skills of creativity that
      are needed for innovation. One audit of history suggests that much can be
      achieved if such qualities are possessed or can be developed by those who also
      'look both ways'.

PMID- 17501878
TI  - Mechanical compression in the prophylaxis of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is an important cause of morbidity and mortality in
      a substantial number of the Australian community. There exists a considerable
      range of potential prophylactic measures aimed at reducing the risk of VTE. These
      antithrombotic regimens include pharmacological interventions and mechanical
      techniques to counteract venous stasis including graduated compression stockings
      and intermittent pneumatic compression (IPC) devices. This review particularly
      concentrates on evidence for the use of mechanical prophylaxis and the
      interrelationship with pharmacological methods of VTE prophylaxis. Mechanical and
      pharmacological methods of VTE prophylaxis are both effective and when used in
      combination have synergistic effects. Although there are a number of different
      IPC systems, little evidence is available at present that differentiates these on
      the basis of VTE prevention. Compliance and patient acceptance of IPC as a
      preventative measure has improved with miniaturization and device weight
      reduction. IPC should be used according to recommended guidelines. In moderate
      risk patients when pharmacological prophylaxis is contraindicated, IPC can be
      used as an alternative. High-risk patients should receive both mechanical and
      pharmacological prophylaxis to reduce their relative risk. Until further evidence
      becomes available, the specific type of IPC unit chosen will generally be
      determined by ease of use, availability and cost.

PMID- 17501879
TI  - Periprosthetic femoral fractures after total hip arthroplasty.
AB  - BACKGROUND: The management of periprosthetic fracture following a total hip
      arthroplasty is difficult, requiring expertise in both trauma and revision
      surgery. With rising numbers of patients in the population living with hip
      prostheses in situ, the frequency of these fractures is increasing, and
      controversy remains over their ideal management. The objective of this study was
      to review all periprosthetic fractures at a single institution to identify injury
      and treatment patterns and their associated clinical outcomes. METHODS: Fifty
      four periprosthetic fractures in 50 patients were reviewed to determine the
      relative frequency of fracture types, their complication rates and the clinical
      outcomes. Patient data were obtained through review of the clinical notes and
      individual patient follow up. Clinical outcomes were evaluated using the Oxford
      Hip Score and Harris Hip Score. RESULTS: The 54 fractures were classified using
      the Vancouver system, most of which were type B1 (20) or type B2 (10). The mean
      time to union for all fracture types was 4.6 months. A high non-union rate was
      seen among fractures fixed operatively. Fifteen per cent of fractures went on to
      develop loosening following treatment, suggesting an underrecognition at the time
      of injury. The average Harris Hip Score was 73.1 and Oxford Hip Score 30.3 for
      all fracture types at a mean follow up of 3.3 years. In the 15 patients treated
      with revision surgery, the most common complication was dislocation (27%).
      CONCLUSION: Treatment of patients with periprosthetic fractures requires
      recognition of the challenging nature of these injuries, the associated poor
      prognosis and the high complication rate.

PMID- 17501880
TI  - Preoperative beta-blocker use reduces atrial fibrillation in off-pump coronary
      bypass surgery.
AB  - BACKGROUND: Atrial fibrillation (AF) after coronary artery bypass graft surgery
      constitutes the most common sustained arrhythmia and results in many
      complications. The purpose of this study was to assess the effects of
      prophylactic use of beta-blockers against atrial fibrillation in off-pump surgery
      patients in the early postoperative period. METHODS: From 2002 to 2005, 78
      patients were enrolled and 41 patients received 50 mg metoprolol succinate daily,
      which was initiated minimum four days before surgery. Preoperative beta-blocking
      therapy was continued until the morning of surgery. Thirty-seven patients were
      free of beta-blocker therapy. Esmolol was used within same range of doses in both
      groups during operations. Both groups received metoprolol succinate following
      operations. The frequency of AF occurrence was analysed from the operation time
      to the sixth postoperative day. RESULTS: Sixteen patients developed AF with an
      overall incidence of 22.5%. Four patients from the study group and three patients
      from the control group were excluded from the study because of transfer to on
      pump surgery. There was no difference with regard to the number of grafts carried
      out, duration of operations and ventilation, intensive care unit stay and
      inotropic need among groups. Length of hospital stay did not differ among groups
      either. There was a higher incidence of postoperative AF in patients without beta
      blocker prophylaxis (11.7-32.4% P=0.049). CONCLUSION: Low-dose postoperative beta
      adrenergic blockade is valuable for patients who receive these medications before
      off-pump coronary artery bypass grafting procedures and may be beneficial against
      AF in all patients.

PMID- 17501881
TI  - Perioperative high-dose oxygen therapy in vascular surgery.
AB  - BACKGROUND: Patients undergoing infrainguinal bypass surgery have reduced
      baseline tissue oxygen tension and high rates of wound infections. The hypoxaemia
      worsens during surgery, potentially reducing the ability to combat bacterial
      lodgement. We investigated whether high-dose perioperative oxygen administration
      to patients undergoing infrainguinal arterial surgery results in increased tissue
      oxygenation. METHODS: Ten consecutive patients undergoing infrainguinal arterial
      surgery had transcutaneous partial pressure of oxygen (TcpO(2)) measured
      preoperatively, intraoperatively after arterial clamps applied, postoperatively
      and at discharge. Measurements were taken with inspired oxygen concentration
      (F(i)O(2)) of 30% then 80%. Arterial blood gases were measured at the same times.
      RESULTS: Tissue oxygenation showed no difference intraoperatively while arterial
      clamps were in place, but significantly higher tissue oxygenation was seen with
      use of high-dose oxygen (F(i)O(2) 80%) postoperatively (P<0.05). Carbon dioxide
      levels in tissue increased while arterial clamps were in place (P<0.01) and pH
      fell intraoperatively and following reperfusion (P<0.05). CONCLUSION: The
      administration of high-dose oxygen to vascular surgical patients undergoing lower
      limb arterial surgery results in increased tissue oxygen concentrations when
      perfusion is not reduced by the presence of arterial clamps. These results
      suggest the administration of high-dose oxygen intraoperatively may be beneficial
      in reducing wound infections, but further research is required.

PMID- 17501882
TI  - The length of superficial temporal artery biopsies.
AB  - BACKGROUND: To compare temporal artery biopsy specimen lengths from a tertiary
      care and a community hospital in New South Wales to recommended clinical
      guidelines in suspected giant cell arteritis. DESIGN: A retrospective
      observational study of all patients who underwent temporal artery biopsy at
      Bathurst Base Hospital (BBH) and Royal Prince Alfred Hospital (RPAH) over a 5
      year period. METHODS: Patients who underwent temporal artery biopsy during the 5
      year period were identified using computerized hospital databases. A
      retrospective chart review was carried out on all cases. Data were collected
      regarding patient age, patient sex, length of biopsy specimen, histopathological
      results and surgical team carrying out the biopsy. RESULTS: During the 5-year
      period, 157 temporal artery biopsies were carried out at both hospitals, with
      38/157(24%) at BBH and 119/157 (76%) at RPAH. There was no significant difference
      in biopsy length at the two hospitals. The mean specimen length at BBH was 12.1
      mm compared with 11.7 mm at RPAH (t=0.35; P=0.73). At RPAH, there was no
      significant difference in specimen length between the surgical specialties
      carrying out the biopsy (ANOVA F=1.37; P=0.26). Specimens of length 20 mm or
      greater were 2.8 times more likely to show features of giant cell arteritis than
      those less than 20 mm. CONCLUSION: The mean length of temporal artery biopsy
      specimens at both hospitals was substantially shorter than recommended guidelines
      of a minimum 20 mm. We recommend all surgeons carrying out temporal artery
      biopsies ensure a specimen of sufficient length is obtained.

PMID- 17501883
TI  - Laparoscopic bile duct exploration: results of 160 consecutive cases with 2-year
      follow up.
AB  - BACKGROUND: Despite numerous reports showing the advantages of laparoscopic
      common bile duct exploration (LCBDE), many general surgeons, particularly those
      working outside of nonspecialist units, continue to rely heavily on endoscopic
      retrograde cholangiography with sphincterotomy (ERCP) to manage bile duct stones
      (BDS). This article investigates the performance of LCBDE when adopted as the
      preferred first-line management of both suspected and incidental BDS by general
      surgeons in a regional setting. METHODS: A retrospective review was conducted of
      all patients in whom LCBDE was attempted by a regional general surgical unit. The
      unit policy was to preferentially treat all incidental and suspected BDS (except
      in ascending cholangitis or severe pancreatitis) by LCBDE, with ERCP used only if
      unsuccessful. In addition to chart review, formal prospective follow up by
      telephone interview was carried out. RESULTS: A total of 160 consecutive patients
      with BDS (mean age 66.9 years, 65% suspected and 35% incidental) underwent
      attempted LCBDE between January 2000 and July 2005. Successful clearance was
      achieved in 84.3% according to chart review. However, four additional cases of
      retained choledocholithiasis shown by late telephone interview (median interval
      2.5 years) yielded a more accurate clearance rate of 81.8%. Major morbidity
      occurred in 13.8%, including biliary leak in 7.5% and one late biliary stricture
      (0.6%). Median length of hospital stay was 4.8 days. In-hospital mortality was
      0.6%. CONCLUSION: Laparoscopic common bile duct exploration remains an effective,
      efficient and safe first-line treatment of BDS even when carried out in regional
      nonspecialist units. In spite of the wide availability of ERCP, general surgeons
      should be encouraged to continue performing LCBDE in order to optimise patient
      care and maintain important surgical skills.

PMID- 17501884
TI  - Rise of colorectal cancer in Singapore: an epidemiological review.
AB  - BACKGROUND: Over the past three decades, Singapore has seen a dramatic increase
      in the incidence of colorectal cancer and this is now the most frequent cancer
      when both genders are combined. METHODS: In light of this alarming trend, a
      review of colorectal cancer in Singapore was conducted, using data from the
      Singapore Cancer Registry from 1968 to 2002. Our research has shown that among
      Southeast Asian countries, Singapore has the highest age-standardized incidence
      rates, 35.1% in men and 29.9% in women, more than twice that of the next country;
      these rates have been increasing at a startling average annual rate of
      approximately 2.6 and 2.35%, for men and women, respectively. RESULTS: Between
      1998 and 2002, deaths from colorectal cancer constituted 19% of all cancer
      mortalities in men and 14% in women, accounting for the second highest cause of
      cancer mortality in both genders. In the same period, more than three quarters
      (75.6%) of colorectal cancers occurred in the distal colon (including splenic
      flexure, descending, sigmoid colon and rectum), with the predominant histological
      subtype being adenocarcinoma (approximately 90%). The age-specific rates for
      colorectal cancer begin to increase sharply in the 40- to 45-year age group. It
      remains the most common primary site of cancer in men aged between 35 and 64
      years but lies a distant second after breast cancer in women. In individuals aged
      65 years and above, colorectal cancer remains prominent in both genders.
      CONCLUSION: Despite the dramatic increase in incidence of colorectal cancer in
      Singapore, there has also been significant progress in survival of colorectal
      cancer patients with localized disease (limited to large bowel), with 5-year, age
      standardized relative survival improving from 36 to 66% in men and 32 to 71% in
      women; in rectal cancer, improvements from 25 to 66% in men and 23 to 66% in
      women were also observed. Similar improvements were noted in patients with
      regional disease (lymph node involvement) but not with distant metastases. This
      has paralleled the dramatic national development in socioeconomic and health-care
      services.

PMID- 17501885
TI  - Cystic change in thyroid cancer.
AB  - BACKGROUND: To determine the incidence of cystic change of thyroid cancer
      detected by ultrasonography and to compare the diagnostic accuracy of fine-needle
      aspiration cytology (FNAC) postultrasonography in solid and cystic thyroid
      nodules. METHODS: This retrospective study collected data for 6219 patients with
      thyroid nodules. Mean patient age was 49.7 +/- 13.6 years. Of these 6219
      patients, 1983 had cystic changes of thyroid nodules and 4236 had solid masses as
      detected by ultrasonography. Following FNAC, 506 of the patients with solid
      masses (11.9%) underwent surgical treatment, compared with 143 of those with
      cystic change of thyroid masses (7.2%). RESULTS: Of the 649 nodules treated
      surgically in the solid and cystic change groups, 29.8% (151/506) and 9.1%
      (13/143) were malignant, respectively. Overall, after surgical treatment, 0.65%
      of cystic changes to thyroid lesions were diagnosed as thyroid cancer. Diagnostic
      accuracy of FNAC in cystic changes of the thyroid masses after ultrasonographic
      examination resembled that in solid thyroid nodules. CONCLUSIONS: Cystic changes
      of thyroid masses are common. Positive predictive value in diagnosing papillary
      carcinoma of thyroid masses with cystic changes is high. Notably, preoperative
      accurate diagnosis is difficult.

PMID- 17501886
TI  - Extravisceral primary hydatid cyst of the retroperitoneum.
AB  - BACKGROUND: Hydatid cyst (HC) continues to be endemic in the Mediterranean
      countries, such as Turkey. Living in a rural area is an important risk factor for
      the disease. HC is most commonly seen in the liver and lungs, but retroperitoneal
      hydatid cyst is very rare. The objective of this study was to evaluate the
      clinical and radiographic findings and surgical treatment of this unusual lesion.
      METHODS: Between 1979 and 2004, 14 cases with primary retroperitoneal hydatid
      cyst were treated surgically at our clinic. RESULTS: Symptoms included flank pain
      in eight (57.1%) and palpable mass in six patients (42.8%). The cyst was located
      in the right retroperitoneum in seven patients (50%), left retroperitoneum in
      five patients (35.7%), retrovesical region in one patient (7.1%) and paravesical
      region in one patient (7.1%). Surgical approaches were right paramedian
      extraperitoneal approach in four patients, left paramedian extraperitoneal
      approach in two patients and midline transperitoneal approach in eight patients.
      Total pericystectomy was chosen as the surgical procedure in all patients except
      in five (35.7%), who had partial cystectomy for cysts located near the vital
      structures. There were no complications and mortality postoperatively.
      CONCLUSION: A primary HC of the retroperitoneum is a distinct clinical entity
      that must be considered when caring for a patient with a retroperitoneal mass in
      endemic regions. It should be treated after the diagnosis is confirmed without
      any delay because of secondary spillages due to perforations and other possible
      complications.

PMID- 17501888
TI  - Cancer stem cells: a review.
AB  - Research has been increasing in recent years into the application of stem cell
      biology to clinical medicine, particularly its role in the evolution and
      metastasis of tumours. Stem cells may be the target cell for malignant
      transformation, and tumour formation could be considered a disorder of stem cell
      self-renewal pathways. Cancer stem cells have been identified in acute myeloid
      leukaemia and in breast and central nervous system tumours. Cancer stem cells may
      have a specific role in tumour metastasis, and their understanding may provide
      insights into the development of predictive and prognostic markers and specific
      therapeutic interventions.

PMID- 17501887
TI  - Randomized trial of skin closure after laparotomy for gynaecological surgery.
AB  - BACKGROUND: New suture materials may provide patients with a better cosmetic
      outcome at similar pain and wound complication rate. METHODS: To assess pain and
      cosmetic outcome among patients randomized to receive wound closure after
      laparotomy for gynaecological surgery using staples, polyglecaprone 25 or
      polyglecaprone 6211 subcuticular sutures. RESULTS: Overall, 90 patients (87.4%
      consent rate) were randomized. There was no difference in wound complications and
      pain between the three groups. Patients randomized to polyglecaprone 6211
      subcuticular sutures rated the cosmetic result at 1 and 6 weeks after surgery
      somewhat lower than patients randomized to the two alternative groups; however,
      at 3 months after surgery, all three groups rated the cosmetic result as similar.
      CONCLUSIONS: This study suggests that the three wound closure methods have
      similar short-term pain and cosmetic outcomes, as well as a similar rate of wound
      complications, leaving the decision of the most appropriate closure method to
      individual surgeons.

PMID- 17501889
TI  - Induction of bone marrow CD34+ cells and endothelialization of
      polytetrafluoroethylene prostheses.
AB  - BACKGROUND: The aim of the study was to investigate the endothelialization of
      prostheses with bone marrow CD34(+) cells. METHODS: CD34(+) cells were isolated
      from the canine bone marrow by an immune magnetic cell sorting system and induced
      into endothelial cells (EC) with vascular endothelial growth factor. Cells were
      seeded to polytetrafluoroethylene prostheses, which were implanted into the
      abdominal aorta artery and inferior vena cava. RESULTS: The isolated cells
      derived from bone marrow were CD34(+) cells by flow cytometry, which could
      differentiate into EC when induced by vascular endothelial growth factor. The
      neointima on control prostheses was significantly thicker than that on prostheses
      seeded with EC at the anastomosis and the centre where the prosthesis interposed
      to aorta. All control prostheses (4/4) interposed to veins were occlusive and two
      seeded prostheses (2/8) interposed to veins were already occluded. The overall
      occlusion rate of prostheses interposed to veins in seeded prostheses and control
      prostheses were 25 and 100%, respectively. However, the neointima on seeded
      prostheses was significantly thicker in the vein than that in the aorta.
      CONCLUSION: Bone marrow CD34(+) cells can be induced into EC by vascular
      endothelial growth factor in vitro. Polytetrafluoroethylene prostheses seeded
      with CD34(+) cells have the ideal endothelialization and patency.

PMID- 17501890
TI  - Pancreatic injury after thoracoabdominal aortic occlusion in a porcine model.
AB  - BACKGROUND: The aim of this study was to investigate pancreatic injury after 45
      min of thoracoabdominal aortic occlusion in a porcine model. METHODS: Twenty-four
      pigs were used. Six pigs underwent sham operation and 18 intravascular balloon
      thoracoabdominal aortic occlusions for 45 min. The animals were randomly killed
      at 12, 48 and 120 h after reperfusion. After killing, all pancreata were examined
      macroscopically for any signs of acute pancreatitis, whereas gland specimens were
      harvested for histological study to evaluate pancreatic injury (haematoxylin and
      eosin staining) and acinar cell apoptosis (Terminal deoxynucleotidyl transferase
      mediated dUTP Nick-End Labelling staining). RESULTS: Pancreatic injury severity
      score was mildly increased in terms of oedematous features at 12 h after
      reperfusion, but normalized to sham levels by the second day and thereafter.
      Necrotic injury was not statistically significant at any time point. Acinar cell
      apoptotic index was mildly increased at 12 and 48 h, but showed a tendency to
      decrease towards sham levels by the fifth day. One animal developed acute
      pancreatitis. CONCLUSION: Acute pancreatitis is unlikely to occur after 45 min of
      thoracoabdominal aortic occlusion. However, an early, mild oedematous and
      apoptotic injury that occurs subclinically seems to be a constant event. This
      injury might have clinical significance when combined with pre-existent
      pancreatic pathologies.

PMID- 17501891
TI  - InLine radiofrequency ablation-assisted laparoscopic liver resection: first
      experiment with stapling device.
AB  - BACKGROUND: In liver surgery, the increase in advancement of laparoscopic
      equipment has allowed the feasibility and safety of complex laparoscopic liver
      resection. However, blood loss and the potential risk of gas embolism seem to be
      the main obstacles. In this study, we successfully used the InLine radiofrequency
      ablation (RFA) device to carry out laparoscopic hand-assisted liver resection in
      pigs. METHODS: Under general anaesthesia with tracheal intubation, pigs underwent
      InLine RFA-assisted laparoscopic liver resection. After installation of Hand Port
      and trocars, the InLine RFA device was introduced through Hand Port system and
      inserted into the premarked resection line. Then the generator was turned on and
      the power was applied according to the power setting. The resection was finally
      carried out using diathermy or stapler. For the control group, resection was
      simply carried out by diathermy or stapler. RESULTS: Eight Landrace pigs
      underwent 23 liver resections. Blood loss was reduced significantly in the InLine
      group (P<0.001) when compared with control group in both surgical methods
      (diathermy and stapler). CONCLUSION: In this study, we successfully carried out
      InLine RFA-assisted laparoscopic liver resection in both stapled and diathermy
      group. We showed that there was a highly significant difference between InLine
      and other liver resection techniques laparoscopically.

PMID- 17501896
TI  - Unusual case of acute abdomen: giant colonic diverticulum.

PMID- 17501897
TI  - Non-steroidal anti-inflammatory drug-induced small bowel diaphragm disease.

PMID- 17501898
TI  - First report of congenital cholesteatoma in an Indigenous Australian child.

PMID- 17501899
TI  - Nodular cystic metastatic basal cell carcinoma: a rare occurrence.

PMID- 17501900
TI  - What's in a name.

PMID- 17501901
TI  - Epididymal tuberculosis: presentations and diagnosis.

PMID- 17501902
TI  - Suction drain retention sutures in the closure of the acute burst abdomen.

PMID- 17501903
TI  - Ascending aortic rupture behind a sternal radionecrosis for breast cancer.

PMID- 17501904
TI  - Hox genes in time and space during vertebrate body formation.
AB  - Vertebrae display distinct morphological features at different levels of the body
      axis. Links between collinear Hox gene activation and the progressive mode of
      body axis elongation have provided a fascinating blueprint of the mechanisms for
      establishing these morphological identities. In this review, we first discuss the
      regulation and possible role of collinear Hox gene activation during body
      formation and then highlight the direct role of Hox genes in controlling cellular
      movements during gastrulation, therefore contributing to body formation.
      Additional related research aspects, such as imaging of chromatin regulation,
      roles of micro RNAs and evolutional findings are also discussed.

PMID- 17501905
TI  - Mathematical and experimental insights into the development of the enteric
      nervous system and Hirschsprung's disease.
AB  - The vertebrate enteric nervous system is formed by a rostro-caudally directed
      invasion of the embryonic gastrointestinal mesenchyme by neural crest cells.
      Failure to complete this invasion results in the distal intestine lacking
      intrinsic neurons. This potentially fatal condition is called Hirschsprung's
      Disease. A mathematical model of cell invasion incorporating cell motility and
      proliferation of neural crest cells to a carrying capacity predicted invasion
      outcomes to imagined manipulations, and these manipulations were tested
      experimentally. Mathematical and experimental results agreed. The results show
      that the directional invasion is chiefly driven by neural crest cell
      proliferation. Moreover, this proliferation occurs in a small region at the
      wavefront of the invading population. These results provide an understanding of
      why many genes implicated in Hirschsprung's Disease influence neural crest
      population size. In addition, during in vivo development the underlying gut
      tissues are growing simultaneously as the neural crest cell invasion proceeds.
      The interactions between proliferation, motility and gut growth dictate whether
      or not complete colonization is successful. Mathematical modeling provides
      insights into the conditions required for complete colonization or a
      Hirschsprung's-like deficiency. Experimental evidence supports the hypotheses
      suggested by the modeling.

PMID- 17501906
TI  - Distinct hemogenic potential of endothelial cells and CD41+ cells in mouse
      embryos.
AB  - Definitive hematopoietic progenitor cells have been thought to develop from the
      vascular endothelium located in the aorta-gonad-mesonephros region of the mouse
      embryo. However, several recent findings have suggested that most hematopoietic
      progenitors are derived from non-endothelial precursor cells expressing CD41. We
      characterized two distinct precursor populations of definitive hematopoietic cell
      lineages, vascular endothelial (VE)-cadherin(+) CD41(-) CD45(-) endothelial cells
      and CD41(+) CD45(-) non-endothelial progenitors, both of which are derived from
      lateral mesoderm. VE-cadherin(+) endothelial cells obtained from cultures of
      differentiating embryonic stem cells possessed hematopoietic potential
      encompassing erythroid, myeloid and B lymphoid lineages, whereas CD41(+)
      progenitors lacked the B lymphopoietic potential. VE-cadherin(+) endothelial
      cells in the lower trunk of the embryo proper showed a significant potential for
      initiating B lymphopoiesis in cultures, while endothelial cells in the yolk sac
      appeared to have a bias for myeloerythropoietic differentiation. CD41(+)
      progenitors isolated from yolk sac and embryo proper were capable of generating
      multiple hematopoietic lineages, although mast cell precursors were exclusively
      enriched in CD41(+) progenitors in the yolk sac. These results suggest that
      hemogenic endothelial cells and CD41(+) progenitors possess distinct
      hematopoietic potential depending on the tissues in which they reside.

PMID- 17501907
TI  - Development of the embryo, larva and early juvenile of Nile tilapia Oreochromis
      niloticus (Pisces: Cichlidae). Developmental staging system.
AB  - We described the developmental stages for the embryonic, larval and early
      juvenile periods of Nile tilapia Oreochromis niloticus to elucidate sequential
      events of craniofacial development. Craniofacial development of cichlids,
      especially differentiation and morphogenesis of the pharyngeal skeleton,
      progresses until about 30 days postfertilization (dpf). Because there is no
      comprehensive report describing the sequential processes of craniofacial
      development up to 30 dpf, we newly defined 32 stages using a numbered staging
      system. For embryonic development, we defined 18 stages (stages 1-18), which were
      grouped into seven periods named the zygote, cleavage, blastula, gastrula,
      segmentation, pharyngula and hatching periods. For larval development, we defined
      seven stages (stages 19-25), which were grouped into two periods, early larval
      and late larval. For juvenile development until 30 dpf, we defined seven stages
      (stages 26-32) in the early juvenile period. This developmental staging system
      for Nile tilapia O. niloticus will benefit researchers investigating
      skeletogenesis throughout tilapia ontogeny and will also facilitate comparative
      evolutionary developmental biology studies of haplochromine cichlids, which
      comprise the species flocks of Lakes Malawi and Victoria.

PMID- 17501908
TI  - Characterization of histone lysine-specific demethylase in relation to thyroid
      hormone-regulated anuran metamorphosis.
AB  - The thyroid hormone receptor (THR) is a member of the nuclear transcription
      factor and plays a central role in regulating anuran metamorphosis. Previous
      studies with mammalian cells have suggested that THR is involved in chromatin
      remodeling through histone methylation. In the present study, we cloned cDNA of
      lysine-specific demethylase gene, xLSD1, from Xenopus laevis and examined its
      expression in relation to metamorphosis. Overexpression of xLSD1 in A6 cells, a
      Xenopus laevis cell line, resulted in the decrease of methylation status of
      lysine residues of histone H3, indicating that the protein of cloned xLSD1 was
      functionally active. The expression of LSD1 at mRNA levels was up-regulated in
      the body skin and the intestine during natural and thyroid hormone-induced
      metamorphosis. Larval epidermal basal cells and intestinal epithelial cells at
      the premetamorphic stage were identified as the xLSD1-expressing cells. At the
      metamorphic climax stage the progenitor cells of adult epidermal basal cells also
      expressed xLSD1, whereas those of the adult intestinal epithelial cells did not.
      We propose that LSD1 participates in the regulation of metamorphosis through THR-
      or another transcriptional factor-induced chromatin remodeling.

PMID- 17501909
TI  - Inheritance of two M type mitochondrial DNA from sperm and unfertilized eggs to
      offspring in Mytilus galloprovincialis.
AB  - In Mytilus mussels, paternal mitochondrial DNA (mtDNA) from sperm is known to be
      transmitted to offspring. This phenomenon is called doubly uniparental
      inheritance (DUI). Under DUI, sperm mtDNA (M type) is inherited only by males.
      Female mussels receive maternal mtDNA (F type). However, in our previous study,
      we showed female and unfertilized eggs have both F and M types. We hypothesized
      that the two M types both from sperm and unfertilized eggs were transmitted to
      offspring. To test the hypothesis, we examined the number of M type haplotypes in
      mature M. galloprovincialis. The M type in larvae was compared with those of the
      parents. Cross experiments were carried out to test the inheritance of M type. In
      six of 20 mature mussels, two M types were detected by sequence analysis and
      polymerase chain reaction-restriction fragment length polymorphism. In cross
      experiments of larval samples from five of 12 crosses, double peak wave was
      observed by single nucleotide polymorphisms analysis. In these larval samples,
      the higher peak wave was identical to the parental M type. Larvae received much
      more paternal M type than the maternal ones. We demonstrated that two M types
      from sperm and unfertilized eggs were transmitted to offspring in M.
      galloprovincialis.

PMID- 17501910
TI  - Bone morphogenetic protein is required for dorso-ventral patterning in the
      planarian Dugesia japonica.
AB  - In order to clarify the function of the Djbmp (Dugesia japonica bone
      morphogenetic protein) gene in planarian body patterning, we carried out
      knockdown of this gene by RNA interference. When the planarians were treated with
      double-stranded RNA of Djbmp, a bulge formed on the dorsal side, with a dent in
      the middle of the bulge, and the body surface inside the dent was smoothened and
      less pigmented. In situ hybridization of the DjIFb gene, which is expressed in
      the body margin, revealed that the additional body margin was formed ectopically
      at the region surrounding the dent. The Djbmp-knockdown planarians often had a
      pair of incomplete nerve cords in the dorsal side, in addition to the original
      pair of ventral nerve cords. Taken together, we concluded that the Djbmp
      knockdown induced formation of an ectopic ventral side, suggesting that Djbmp is
      required for the dorso-ventral body patterning in the planarian.

PMID- 17501911
TI  - Expression of Thy 1.2 surface antigen increases significantly during the murine
      mesenchymal stem cells cultivation period.
AB  - This study sought to investigate the absence or expression of some surface
      antigens on murine mesenchymal stem cells (mMSCs) during the cultivation period
      of primary culture to passage 3 (equivalent to about 15 or 16 population doubling
      number). For this purpose, bone marrow cells from 6-8-week-old mice (either NMRI
      or Balb/c) were cultivated in 75-cm(2) culture flask for three successive
      passages, in each of which the culture was examined for the expression of CD135,
      CD44, CD31, Thy1.2, CD11b, CD45, CD34, Vcam1, Sca-1, and c-Kit antigens, using
      flow cytometry. Passage-3 cells from each strain can easily be differentiated
      into bone and fat, which was indicative of their mesenchymal nature. Our results
      demonstrated that for each given antigen, the percentages of the cells expressing
      that antigen had been changed by subcultures. The statistical analysis showed
      that nearly all differences between the passages were statistically significant.
      In this term, the expressional changes of Thy 1.2 seemed to be very significant
      in such a way that the expression increased to about half of the whole population
      in passage 3. In conclusion, it seems that this antigen could be considered as an
      enriching antigen for mMSCs population from bone marrow adherent cell culture.

PMID- 17501912
TI  - How to build a fungal fruit body: from uniform cells to specialized tissue.
AB  - It is a challenge in biology to explore the molecular and cellular mechanisms
      necessary to form a complex three-dimensional structure composed of different
      cell types. Interesting models to study the underlying processes are fungi that
      can transform their wire-like hyphal filaments into complex and sometimes
      container-like fruit bodies. In the past, the role of developmental triggers and
      transcription factors was a major focus of research on fungal model organisms. In
      this issue of Molecular Microbiology, Nowrousian and collaborators report that
      fruit body development of the model organism Sordaria macrospora includes a novel
      player, a specific membrane protein of the endoplasmic reticulum that is not
      required for vegetative growth. This finding represents an important step towards
      connecting regulation of development with the co-ordinated changes in cellular
      compartments.

PMID- 17501913
TI  - Cell wall growth during elongation and division: one ring to bind them?
AB  - The role of the cell division protein FtsZ in bacterial cell wall (CW) synthesis
      is believed to be restricted to localizing proteins involved in the synthesis of
      the septal wall. In this issue of Molecular Microbiology, the groups of Christine
      Jacobs-Wagner and Waldemar Vollmer provide compelling evidence that in
      Caulobacter crescentus, FtsZ plays an additional role in CW synthesis in non
      dividing cells. During elongation (cell growth) FtsZ is responsible for the
      incorporation of CW material in a zone at the midcell by recruiting MurG, a
      protein involved in peptidoglycan (PG) precursor synthesis. This resembles
      earlier findings of FtsZ mediated PG synthesis activity in Escherichia coli. A
      role of FtsZ in PG synthesis during elongation forces a rethink of the current
      model of CW synthesis in rod-shaped bacteria.

PMID- 17501914
TI  - Laboratory strains of Escherichia coli: model citizens or deceitful delinquents
      growing old disgracefully?
AB  - Escherichia coli stands unchallenged as biology's premier model organism.
      However, we propose, equipped with insights from the post-genomic era, a contrary
      view: that microbiology's chief idol has feet of clay. E. coli laboratory
      strains, particularly E. coli K-12, are far from model citizens, but instead
      degenerate and deceitful delinquents growing old disgracefully in our scientific
      institutions. E. coli K-12 is neither archetype nor ancestor. In addition, it has
      a far from optimal provenance for a model organism, with strong grounds for
      believing that current versions of the strain are quite distinct from any
      original wild-type free-living ancestor. In addition, it is usually studied under
      conditions far removed from its natural habitats and in ignorance of the
      selective pressures that have shaped its evolution. Fortunately, a flood of
      information from high-throughput genome sequencing, together with a new 'eco-evo'
      view of this model organism, promises to help put K-12 better into context.

PMID- 17501916
TI  - Suicide prevention: disruption of apoptotic pathways by protozoan parasites.
AB  - The modulation of apoptosis has emerged as an important weapon in the pathogenic
      arsenal of multiple intracellular protozoan parasites. Cryptosporidium parvum,
      Leishmania spp., Trypanosoma cruzi, Theileria spp., Toxoplasma gondii and
      Plasmodium spp. have all been shown to inhibit the apoptotic response of their
      host cell. While the pathogen mediators responsible for this modulation are
      unknown, the parasites are interacting with multiple apoptotic regulatory systems
      to render their host cell refractory to apoptosis during critical phases of
      intracellular infection, including parasite invasion, establishment and
      replication. Additionally, emerging evidence suggests that the parasite life
      cycle stage impacts the modulation of apoptosis and possibly parasite
      differentiation. Dissection of the host-pathogen interactions involved in
      modulating apoptosis reveals a dynamic and complex interaction that recent
      studies are beginning to unravel.

PMID- 17501915
TI  - Viral nanomotors for packaging of dsDNA and dsRNA.
AB  - While capsid proteins are assembled around single-stranded genomic DNA or RNA in
      rod-shaped viruses, the lengthy double-stranded genome of other viruses is
      packaged forcefully within a preformed protein shell. This entropically
      unfavourable DNA or RNA packaging is accomplished by an ATP-driven viral
      nanomotor, which is mainly composed of two components, the oligomerized channel
      and the packaging enzymes. This intriguing DNA or RNA packaging process has
      provoked interest among virologists, bacteriologists, biochemists, biophysicists,
      chemists, structural biologists and computational scientists alike, especially
      those interested in nanotechnology, nanomedicine, AAA+ family proteins, energy
      conversion, cell membrane transport, DNA or RNA replication and antiviral
      therapy. This review mainly focuses on the motors of double-stranded DNA viruses,
      but double-stranded RNA viral motors are also discussed due to interesting
      similarities. The novel and ingenious configuration of these nanomotors has
      inspired the development of biomimetics for nanodevices. Advances in structural
      and functional studies have increased our understanding of the molecular basis of
      biological movement to the point where we can begin thinking about possible
      applications of the viral DNA packaging motor in nanotechnology and medical
      applications.

PMID- 17501917
TI  - Chaperoning Anfinsen: the steric foldases.
AB  - Some proteins are so much resistant to proteolysis and unfolding that they
      violate folding rules shared by the vast majority of proteins. These unusual
      proteins manage to fold into an active native conformation that is
      thermodynamically at best marginally, but often even less stable than the
      unfolded state. A huge energetic barrier traps these proteins kinetically in the
      folded state. The drawback of this situation is the need for a specialized
      chaperone that adds steric information to the proteins to cross this barrier on
      the folding pathway. Until now, our knowledge of these intriguing chaperones was
      restricted to the prodomains of secreted proteases, which function
      intramolecularly. Recent research has added more examples, which now include the
      membrane-anchored lipase-specific foldase and the pilus subunit specific
      chaperone, both acting intermolecularly. The case of the pilin chaperone is
      somewhat deviant in that steric information is definitely provided, but the pilus
      subunit adopts a thermodynamically favourable stable conformation.

PMID- 17501919
TI  - The tubulin homologue FtsZ contributes to cell elongation by guiding cell wall
      precursor synthesis in Caulobacter crescentus.
AB  - The tubulin homologue FtsZ is well known for its essential function in bacterial
      cell division. Here, we show that in Caulobacter crescentus, FtsZ also plays a
      major role in cell elongation by spatially regulating the location of MurG, which
      produces the essential lipid II peptidoglycan cell wall precursor. The early
      assembly of FtsZ into a highly mobile ring-like structure during cell elongation
      is quickly followed by the recruitment of MurG and a major redirection of
      peptidoglycan precursor synthesis to the midcell region. These FtsZ-dependent
      events occur well before cell constriction and contribute to cell elongation. In
      the absence of FtsZ, MurG fails to accumulate near midcell and cell elongation
      proceeds unperturbed in appearance by insertion of peptidoglycan material along
      the entire sidewalls. Evidence suggests that bacteria use both a FtsZ-independent
      and a FtsZ-dependent mode of peptidoglycan synthesis to elongate, the importance
      of each mode depending on the timing of FtsZ assembly during elongation.

PMID- 17501918
TI  - The novel ER membrane protein PRO41 is essential for sexual development in the
      filamentous fungus Sordaria macrospora.
AB  - The filamentous fungus Sordaria macrospora develops complex fruiting bodies
      (perithecia) to propagate its sexual spores. Here, we present an analysis of the
      sterile mutant pro41 that is unable to produce mature fruiting bodies. The mutant
      carries a deletion of 4 kb and is complemented by the pro41 open reading frame
      that is contained within the region deleted in the mutant. In silico analyses
      predict PRO41 to be an endoplasmic reticulum (ER) membrane protein, and a PRO41
      EGFP fusion protein colocalizes with ER-targeted DsRED. Furthermore, Western blot
      analysis shows that the PRO41-EGFP fusion protein is present in the membrane
      fraction. A fusion of the predicted N-terminal signal sequence of PRO41 with EGFP
      is secreted out of the cell, indicating that the signal sequence is functional.
      pro41 transcript levels are upregulated during sexual development. This increase
      in transcript levels was not observed in the sterile mutant pro1 that lacks a
      transcription factor gene. Moreover, microarray analysis of gene expression in
      the mutants pro1, pro41 and the pro1/41 double mutant showed that pro41 is partly
      epistatic to pro1. Taken together, these data show that PRO41 is a novel ER
      membrane protein essential for fruiting body formation in filamentous fungi.

PMID- 17501920
TI  - The quorum sensing regulator HapR downregulates the expression of the virulence
      gene transcription factor AphA in Vibrio cholerae by antagonizing Lrp- and VpsR
      mediated activation.
AB  - HapR is a quorum sensing-regulated transcription factor that represses the
      virulence cascade in Vibrio cholerae by binding to a specific site centred at -71
      in the aphA promoter, ultimately preventing activation of the tcpPH promoter on
      the Vibrio pathogenicity island. In an effort to elucidate the mechanism by which
      HapR represses aphA expression, we identified two transcriptional regulators, Lrp
      and VpsR, both of which activate the aphA promoter. Lrp, the leucine-responsive
      regulatory protein, binds to a region between -136 and -123 in the promoter to
      initiate aphA expression. VpsR, the response regulator that controls biofilm
      formation, binds to a region between -123 and -73 to activate aphA expression.
      HapR represses aphA expression by antagonizing the functions of both of these
      activators. The HapR binding site at -71 lies downstream of the Lrp binding site
      and overlaps the VpsR binding site. HapR binding thus directly blocks access of
      VpsR to the promoter. A naturally occurring point mutation in the aphA promoter
      (G-77T), which has previously been shown to prevent HapR binding, also prevents
      VpsR binding. In the absence of HapR, either Lrp or VpsR is capable of achieving
      nearly full expression of the aphA promoter, but when present together their
      effects are to some degree additive. The aphA promoter is also negatively
      autoregulated and an AphA binding site is centred at -20. The results here
      provide a model for the dual activation of the aphA promoter by Lrp and VpsR as
      well as its dual repression by HapR and AphA.

PMID- 17501921
TI  - Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm
      formation.
AB  - Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive human
      pathogen responsible for several acute diseases and autoimmune sequelae that
      account for half a million deaths worldwide every year. GAS infections require
      the capacity of the pathogen to adhere to host tissues and assemble in cell
      aggregates. Furthermore, a role for biofilms in GAS pathogenesis has recently
      been proposed. Here we investigated the role of GAS pili in biofilm formation. We
      demonstrated that GAS pilus-negative mutants, in which the genes encoding either
      the pilus backbone structural protein or the sortase C1 have been deleted, showed
      an impaired capacity to attach to a pharyngeal cell line. The same mutants were
      much less efficient in forming cellular aggregates in liquid culture and
      microcolonies on human cells. Furthermore, mutant strains were incapable of
      producing the typical three-dimensional layer with bacterial microcolonies
      embedded in a carbohydrate polymeric matrix. Complemented mutants had an adhesion
      and aggregation phenotype similar to the wild-type strain. Finally, in vivo
      expression of pili was indirectly confirmed by demonstrating that most of the
      sera from human patients affected by GAS-mediated pharyngitis recognized
      recombinant pili proteins. These data support the role of pili in GAS adherence
      and colonization and suggest a general role of pili in all pathogenic
      streptococci.

PMID- 17501922
TI  - Thiol-disulphide oxidoreductase modules in the low-GC Gram-positive bacteria.
AB  - Disulphide bond formation catalysed by thiol-disulphide oxidoreductases (TDORs)
      is a universally conserved mechanism for stabilizing extracytoplasmic proteins.
      In Escherichia coli, disulphide bond formation requires a concerted action of
      distinct TDORs in thiol oxidation and subsequent quinone reduction. TDOR function
      in other bacteria has remained largely unexplored. Here we focus on TDORs of low
      GC Gram-positive bacteria, in particular DsbA of Staphylococcus aureus and BdbA-D
      of Bacillus subtilis. Phylogenetic analyses reveal that the homologues DsbA and
      BdbD cluster in distinct groups typical for Staphylococcus and Bacillus species
      respectively. To compare the function of these TDORs, DsbA was produced in
      various bdb mutants of B. subtilis. Next, we assessed the ability of DsbA to
      sustain different TDOR-dependent processes, including heterologous secretion of
      E. coli PhoA, competence development and bacteriocin (sublancin 168) production.
      The results show that DsbA can function in all three processes. While BdbD needs
      a quinone oxidoreductase for activity, DsbA activity appears to depend on redox
      active medium components. Unexpectedly, both quinone oxidoreductases of B.
      subtilis are sufficient to sustain production of sublancin. Moreover, DsbA can
      functionally replace these quinone oxidoreductases in sublancin production. Taken
      together, our unprecedented findings imply that TDOR systems of low-GC Gram
      positive bacteria have a modular composition.

PMID- 17501923
TI  - The global regulator H-NS binds to two distinct classes of sites within the Tn10
      transpososome to promote transposition.
AB  - The histone-like nucleoid structuring protein (H-NS) is a global transcriptional
      regulator that influences stress response and virulence pathways in Gram-negative
      bacteria. H-NS also promotes Tn10 transposition by binding directly to the
      transpososome and inducing a conformational change in the transpososome that
      favours intermolecular transposition events. H-NS binds preferentially to curved
      DNA and can bend non-curved DNA, it self-oligomerizes and can interact with other
      proteins. To determine what functions of H-NS are important in promoting Tn10
      transposition, we have examined the ability of two mutant forms of H-NS, P116S
      and 1-64, to act in Tn10 transposition. We provide evidence that the initial
      interaction of H-NS with the transpososome is dependent on H-NS binding to a
      specific structure in DNA flanking the transposon end. Additional molecules of H
      NS then bind within the transposon end. This latter event appears to be directed
      by H-NS binding to the Tn10 transposase protein, and is important in maintaining
      the transpososome in a conformation that promotes intermolecular transposition.
      The binding of H-NS to a transposase protein is a novel function for this
      important regulatory molecule.

PMID- 17501924
TI  - Glycosylphosphatidylinositol (GPI) anchor is required in Aspergillus fumigatus
      for morphogenesis and virulence.
AB  - In yeast, glycosylphosphatidylinositol (GPI) is essential for viability and plays
      an important role in biosynthesis and organization of cell wall. Initiation of
      the GPI anchor biosynthesis is catalysed by the GPI-N
      acetylglucosaminyltransferase complex (GPI-GnT). The GPI3 (SPT14) gene is thought
      to encode the catalytic subunit of GPI-GnT complex. In contrast to Saccharomyces
      cerevisiae, little is known about the GPI biosynthesis in filamentous fungi. In
      this study, the afpig-a gene was identified as the homologue of the GPI3/pig-A
      gene in Aspergillus fumigatus, an opportunistic fungal pathogen. By replacement
      of the afpig-a gene with a pyrG gene, we obtained the null mutants. Although the
      Deltaafpig-a mutant exhibited a significant increased cell lysis instead of
      temperature-sensitive or conditional lethal phenotype associated to the GPI3
      mutant of yeast, they could survive at temperatures from 30 degrees C to 50
      degrees C. The analysis of the mutants showed that a completely blocking of the
      GPI anchor synthesis in A. fumigatus led to cell wall defect, abnormal hyphal
      growth, rapid conidial germination and aberrant conidiation. In vivo assays
      revealed that the mutant exhibited a reduced virulence in immunocompromised mice.
      The GPI anchor was not essential for viability, but required for the cell wall
      integrity, morphogenesis and virulence in A. fumigatus.

PMID- 17501925
TI  - Sequence features of substrates required for cleavage by GlpG, an Escherichia
      coli rhomboid protease.
AB  - Rhomboids are a family of serine proteases belonging to intramembrane cleaving
      proteases, which are supposed to catalyse proteolysis of a substrate protein
      within the membrane. It remains unclear whether substrates of the rhomboid
      proteases have a common sequence feature that allows specific cleavage by
      rhomboids. We showed previously that GlpG, the Escherichia coli rhomboid, can
      cleave a type I model membrane protein Bla-LY2-MBP having the second
      transmembrane region of lactose permease (LY2) at the extramembrane region in
      vivo and in vitro, and that determinants for proteolysis reside within the LY2
      sequence. Here we characterized sequence features in LY2 that allow efficient
      cleavage by GlpG and identified two elements, a hydrophilic region encompassing
      the cleavage site and helix-destabilizing residues in the downstream hydrophobic
      region. Importance of the positioning of helix-destabilizers relative to the
      cleavage site was suggested. These two elements appear to co-operatively promote
      proteolysis of substrates by GlpG. Finally, random mutagenesis of the cleavage
      site residues in combination with in vivo screening revealed that GlpG prefers
      residues with a small side chain and a negative charge at the P1 and P1' sites
      respectively.

PMID- 17501926
TI  - Multiple mechanisms to ameliorate the fitness burden of mupirocin resistance in
      Salmonella typhimurium.
AB  - We examined how the fitness costs of mupirocin resistance caused by mutations in
      the chromosomal isoleucyl-tRNA synthetase gene (ileS) can be ameliorated.
      Mupirocin-resistant mutants were isolated and four different, resistance
      conferring point mutations in the chromosomal ileS gene were identified. Fifty
      independent lineages of the low-fitness, resistant mutants were serially passaged
      to evolve compensated mutants with increased fitness. In 34/50 of the evolved
      lineages, the increase in fitness resulted from additional point mutations in
      isoleucine tRNA synthetase (IleRS). Measurements in vitro of the kinetics of
      aminoacylation of wild-type and mutant enzymes showed that resistant IleRS had a
      reduced rate of aminoacylation due to altered interactions with both tRNAIle and
      ATP. The intragenic compensatory mutations improved IleRS kinetics towards the
      wild-type enzyme, thereby restoring bacterial fitness. Seven of the 16 lineages
      that lacked second-site compensatory mutations in ileS, showed an increase in
      ileS gene dosage, suggesting that an increased level of defective IleRS
      compensate for the decrease in aminoacylation activity. Our findings show that
      the fitness costs of ileS mutations conferring mupirocin resistance can be
      reduced by several types of mechanisms that may contribute to the stability of
      mupirocin resistance in clinical settings.

PMID- 17501927
TI  - A dedicated haem lyase is required for the maturation of a novel bacterial
      cytochrome c with unconventional covalent haem binding.
AB  - In bacterial c-type cytochromes, the haem cofactor is covalently attached via two
      cysteine residues organized in a haem c-binding motif. Here, a novel octa-haem c
      protein, MccA, is described that contains only seven conventional haem c-binding
      motifs (CXXCH), in addition to several single cysteine residues and a conserved
      CH signature. Mass spectrometric analysis of purified MccA from Wolinella
      succinogenes suggests that two of the single cysteine residues are actually part
      of an unprecedented CX15CH sequence involved in haem c binding. Spectroscopic
      characterization of MccA identified an unusual high-potential haem c with a red
      shifted absorption maximum, not unlike that of certain eukaryotic cytochromes c
      that exceptionally bind haem via only one thioether bridge. A haem lyase gene was
      found to be specifically required for the maturation of MccA in W. succinogenes.
      Equivalent haem lyase-encoding genes belonging to either the bacterial cytochrome
      c biogenesis system I or II are present in the vicinity of every known mccA gene
      suggesting a dedicated cytochrome c maturation pathway. The results necessitate
      reconsideration of computer-based prediction of putative haem c-binding motifs in
      bacterial proteomes.

PMID- 17501928
TI  - The RprY response regulator of Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is a Gram-negative oral anaerobe associated with chronic
      adult periodontitis. Its ecological niche is the gingival crevice, where the
      organism adapts to the challenges of the infectious process such as host defence
      and bacterial products. Bacterial responses to environmental changes are partly
      regulated by two-component signal transduction systems. Several intact systems
      were annotated in the genome of P. gingivalis, as well as an orphan regulator
      encoding a homologue of RprY, a response regulator from Bacteroides fragilis.
      With the goal of defining the environmental cues that activate RprY in P.
      gingivalis, we used several strategies to identify its regulon. Results from gene
      expression and DNA-protein binding assays identified target genes that were
      either involved in transport functions or associated with oxidative stress, and
      indicated that RprY can act as an activator and a repressor. RprY positively
      activated the primary sodium pump, NADH : ubiquinone oxidoreductase (NQR), and
      RprY protein also interacted with the promoter regions of nqrA genes from B.
      fragilis and Vibrio cholerae. Given that gingival bleeding and infiltration of
      host defence cells are symptoms of periodontal infection, iron products released
      from blood and reactive oxygen species from polymorphonuclear leucocytes may be
      potential inducers of the RprY regulon.

PMID- 17501929
TI  - Temperature-induced regulation of RpoS by a small RNA in Borrelia burgdorferi.
AB  - The alternative sigma factor RpoS (sigma38 or sigmaS) plays a central role in the
      reciprocal regulation of the virulence-associated major outer surface proteins
      OspC and OspA in Borrelia burgdorferi, the Lyme disease spirochete. Temperature
      is one of the key environmental signals controlling RpoS, but the molecular
      mechanism by which the signal is transduced remains unknown. Herein, we identify
      and describe a small non-coding RNA, DsrABb, that regulates the temperature
      induced increase in RpoS. A novel 5' end of the rpoS mRNA was identified and
      DsrABb has the potential to extensively base-pair with the upstream region of
      this rpoS transcript. We demonstrate that B. burgdorferi strains lacking DsrABb
      do not upregulate RpoS and OspC in response to an increase in temperature, but do
      regulate RpoS and OspC in response to changes in pH and cell density. Analyses of
      the rpoS and ospC steady-state mRNA levels in the dsrABb mutant indicate that
      DsrABb regulates RpoS post-transcriptionally. The 5' and 3' ends of DsrABb were
      mapped, demonstrating that at least four species exist with sizes ranging from
      213 to 352 nucleotides. We hypothesize that DsrABb binds to the upstream region
      of the rpoS mRNA and stimulates translation by releasing the Shine-Dalgarno
      sequence and start site from a stable secondary structure. Therefore, we
      postulate that DsrABb is a molecular thermometer regulating RpoS in Borrelia
      burgdorferi.

PMID- 17501930
TI  - A haem cofactor is required for redox and light signalling by the AppA protein of
      Rhodobacter sphaeroides.
AB  - The AppA protein of Rhodobacter sphaeroides is unique in its ability to sense and
      transmit redox signals as well as light signals. By functioning as antagonist to
      the PpsR transcriptional repressor, it regulates the expression of photosynthesis
      genes in response to these environmental stimuli. Here we show binding of the
      cofactor haem to a domain in the C-terminal part of AppA and redox activity of
      bound haem. This is supported by the findings that: (i) the C-terminal domain of
      AppA (AppADeltaN) binds to haemin agarose, (ii) AppADeltaN isolated from
      Escherichia coli shows absorbance at 411 nm and absorbances at 424 nm and 556 nm
      after reduction with dithionite and (iii) AppADeltaN can be reconstituted with
      haem in vitro. Expression of AppA variants in R. sphaeroides reveals that the
      haem binding domain is important for normal expression levels of photosynthesis
      genes and for normal light regulation in the presence of oxygen. The haem
      cofactor affects the interaction of the C-terminal part of AppA to PpsR but also
      its interaction to the N-terminal light sensing AppA-BLUF domain. Based on this
      we present a model for the transmission of light and redox signals by AppA.

PMID- 17501931
TI  - Transmembrane transport of peptidoglycan precursors across model and bacterial
      membranes.
AB  - Translocation of the peptidoglycan precursor Lipid II across the cytoplasmic
      membrane is a key step in bacterial cell wall synthesis, but hardly understood.
      Using NBD-labelled Lipid II, we showed by fluorescence and TLC assays that Lipid
      II transport does not occur spontaneously and is not induced by the presence of
      single spanning helical transmembrane peptides that facilitate transbilayer
      movement of membrane phospholipids. MurG catalysed synthesis of Lipid II from
      Lipid I in lipid vesicles also did not result in membrane translocation of Lipid
      II. These findings demonstrate that a specialized protein machinery is needed for
      transmembrane movement of Lipid II. In line with this, we could demonstrate Lipid
      II translocation in isolated Escherichia coli inner membrane vesicles and this
      transport could be uncoupled from the synthesis of Lipid II at low temperatures.
      The transport process appeared to be independent from an energy source (ATP or
      proton motive force). Additionally, our studies indicate that translocation of
      Lipid II is coupled to transglycosylation activity on the periplasmic side of the
      inner membrane.

PMID- 17501932
TI  - Transcriptional and physiological adaptation to defective protein-O-mannosylation
      in Candida albicans.
AB  - Five Pmt isoforms O-mannosylate secretory proteins in Candida albicans.
      Comparisons of genome-wide transcript patterns of each pmt mutant revealed
      commonly downregulated genes involved in glycolysis and glycerol production.
      Increased phosphorylation of the Cek1p- but not the Mkc1p-MAP kinase, as well as
      increased transcript levels for some stress-related genes were detected in the
      pmt1 strain but not in the other pmt mutants. The transcriptomal pattern after
      short-term inhibition of Pmt1p activity confirmed stress responses, but did not
      indicate an alteration of glycolytic flow. Short- but not long-term adaptation to
      Pmt1p inhibition required signalling components Cek1p, Mkc1p, Efg1p and Tpk1p.
      Cna1p (calcineurin) but not its downstream effectors Crz1p and Crz2p was
      generally essential to allow growth during Pmt1p inhibition; accordingly,
      cyclosporin A strongly inhibited growth of the pmt1 mutant. The lack of Pmt
      isoforms influenced transcript levels for the remaining isoforms both positively
      and negatively, suggesting complex cross-regulation among PMT genes. These
      results confirm individual functions of Pmt isoforms but suggest a common
      biphasic adaptation response to Pmt deficiency. While known signalling pathways
      modulate adaptation for a short-term, long-term adaptation requires calcineurin,
      adjustments of remaining Pmt activities and of glycolytic flow.

PMID- 17501933
TI  - Identification of a region of FtsA required for interaction with FtsZ.
AB  - The assembly of the Z ring is the earliest step in bacterial cell division. In
      Escherichia coli this assembly requires either FtsA or ZipA which bind to a
      conserved, C-terminal 17 amino acid motif in FtsZ and to the membrane. The FtsZ
      ZipA interaction is well characterized; however, nothing is known about the
      region of FtsA involved in the interaction with FtsZ even though the FtsA-FtsZ
      interaction is nearly ubiquitous in Eubacteria. FtsA is proposed to bind to the
      membrane through its conserved C-terminal amphiphatic helix before efficiently
      interacting with FtsZ. Based upon this model we designed a genetic screen to
      identify mutants specifically impaired for the FtsA-FtsZ interaction. The mutants
      obtained retain the ability to be targeted to the membrane but fail to be
      recruited to the Z ring or interact with FtsZ in the yeast two-hybrid system.
      These mutants do not complement an ftsA-depletion strain. Through this approach
      we have identified a region of FtsA containing some invariant residues which is
      required for binding to FtsZ. The results support our model that FtsA is targeted
      to the membrane before it interacts with FtsZ and demonstrates that this
      interaction plays an essential role in E. coli cell division.

PMID- 17501935
TI  - Evidence for an association of the dopamine D5 receptor gene on age at onset of
      attention deficit hyperactivity disorder.
AB  - The purpose of this study was to determine whether the single nucleotide
      polymorphisms (SNPs) within candidate genes for attention deficit hyperactivity
      disorder (ADHD) are associated with the age at onset for ADHD. One hundred and
      forty-three SNPs were genotyped across five candidate genes (DRD5, SLC6A3, HTR1B,
      SNAP25, DRD4) for ADHD in 229 families with at least one affected offspring. SNPs
      with the highest estimated power to detect an association with age at onset were
      selected for each candidate gene, using a power-based screening procedure that
      does not compromise the nominal significance level. A time-to-onset analysis for
      family-based samples was performed on these SNPs to determine if an association
      exists with age at onset for ADHD. Seven consecutive SNPs surrounding the D5
      dopamine receptor gene (DRD5), were associated with the age at onset for ADHD;
      FDR adjusted q-values ranged from 0.008 to 0.023. This analysis indicates that
      individuals with the risk genotype develop ADHD earlier than individuals with any
      other genotype. A haplotype analysis across the 6 significant SNPs that were in
      linkage disequilibrium with one another, CTCATA, was also found to be significant
      (p-value = 0.02). We did not observe significant associations with age at onset
      for the other candidate loci tested. Although definitive conclusions await
      independent replication, these results suggest that a variant in DRD5 may affect
      age at onset for ADHD.

PMID- 17501936
TI  - Nonparametric inference on median residual life function.
AB  - A simple approach to the estimation of the median residual lifetime is proposed
      for a single group by inverting a function of the Kaplan-Meier estimators. A test
      statistic is proposed to compare two median residual lifetimes at any fixed time
      point. The test statistic does not involve estimation of the underlying
      probability density function of failure times under censoring. Extensive
      simulation studies are performed to validate the proposed test statistic in terms
      of type I error probabilities and powers at various time points. One of the
      oldest data sets from the National Surgical Adjuvant Breast and Bowel Project
      (NSABP), which has more than a quarter century of follow-up, is used to
      illustrate the method. The analysis results indicate that, without systematic
      post-operative therapy, a significant difference in median residual lifetimes
      between node-negative and node-positive breast cancer patients persists for about
      10 years after surgery. The new estimates of the median residual lifetime could
      serve as a baseline for physicians to explain any incremental effects of post
      operative treatments in terms of delaying breast cancer recurrence or prolonging
      remaining lifetimes of breast cancer patients.

PMID- 17501937
TI  - Estimating lead time and overdiagnosis associated with PSA screening from
      prostate cancer incidence trends.
AB  - The introduction of the prostate-specific antigen (PSA) test has led to dramatic
      changes in the incidence of prostate cancer in the United States. In this
      article, we use information on the increase and subsequent decline in prostate
      cancer incidence following the adoption of PSA to estimate the lead time
      associated with PSA screening. The lead time is a key determinant of the
      likelihood of overdiagnosis, one of the main costs associated with the PSA test.
      Our approach conceptualizes observed incidence as the sum of the secular trend in
      incidence, which reflects incidence in the absence of PSA, and the excess
      incidence over and above the secular trend, which is a function of population
      screening patterns and the unknown lead time. We develop a likelihood model for
      the excess incidence given the secular trend and use it to estimate the mean lead
      time under specified distributional assumptions. We also develop a likelihood
      model for observed incidence and use it to simultaneously estimate the mean lead
      time together with a smooth secular trend. Variances and confidence intervals are
      estimated via a parametric bootstrap. Our results indicate an average lead time
      of approximately 4.59 years (95% confidence interval [3.24, 5.93]) for whites and
      6.78 years [5.42, 8.20] for blacks with a corresponding secular trend estimate
      that is fairly flat after the introduction of PSA screening. These estimates
      correspond to overdiagnosis frequencies of approximately 22.7% and 34.4% for
      screen-detected whites and blacks, respectively. Our results provide the first
      glimpse of a plausible secular trend in prostate cancer incidence and suggest
      that, in the absence of PSA screening, disease incidence would not have continued
      its historic increase, rather it would have leveled off in accordance with
      changes in prostate patterns of care unrelated to PSA.

PMID- 17501938
TI  - Efficient estimation for patient-specific rates of disease progression using
      nonnormal linear mixed models.
AB  - This article presents a new class of nonnormal linear mixed models that provide
      an efficient estimation of subject-specific disease progression in the analysis
      of longitudinal data from the Modification of Diet in Renal Disease (MDRD) trial.
      This new analysis addresses the previously reported finding that the distribution
      of the random effect characterizing disease progression is negatively skewed. We
      assume a log-gamma distribution for the random effects and provide the maximum
      likelihood inference for the proposed nonnormal linear mixed model. We derive the
      predictive distribution of patient-specific disease progression rates, which
      demonstrates rather different individual progression profiles from those obtained
      from the normal linear mixed model analysis. To validate the adequacy of the log
      gamma assumption versus the usual normality assumption for the random effects, we
      propose a lack-of-fit test that clearly indicates a better fit for the log-gamma
      modeling in the analysis of the MDRD data. The full maximum likelihood inference
      is also advantageous in dealing with the missing at random (MAR) type of dropouts
      encountered in the MDRD data.

PMID- 17501939
TI  - Matching in studies of classification accuracy: implications for analysis,
      efficiency, and assessment of incremental value.
AB  - In case-control studies evaluating the classification accuracy of a marker,
      controls are often matched to cases with respect to factors associated with the
      marker and disease status. In contrast with matching in epidemiologic etiology
      studies, matching in the classification setting has not been rigorously studied.
      In this article, we consider the implications of matching in terms of the choice
      of statistical analysis, efficiency, and assessment of the incremental value of
      the marker over the matching covariates. We find that adjustment for the matching
      covariates is essential, as unadjusted summaries of classification accuracy can
      be biased. In many settings, matching is the most efficient covariate-dependent
      sampling scheme, and we provide an expression for the optimal matching ratio.
      However, we also show that matching greatly complicates estimation of the
      incremental value of the marker. We recommend that matching be carefully
      considered in the context of these findings.

PMID- 17501940
TI  - Joint models for a primary endpoint and multiple longitudinal covariate
      processes.
AB  - Joint models are formulated to investigate the association between a primary
      endpoint and features of multiple longitudinal processes. In particular, the
      subject-specific random effects in a multivariate linear random-effects model for
      multiple longitudinal processes are predictors in a generalized linear model for
      primary endpoints. Li, Zhang, and Davidian (2004, Biometrics60, 1-7) proposed an
      estimation procedure that makes no distributional assumption on the random
      effects but assumes independent within-subject measurement errors in the
      longitudinal covariate process. Based on an asymptotic bias analysis, we found
      that their estimators can be biased when random effects do not fully explain the
      within-subject correlations among longitudinal covariate measurements.
      Specifically, the existing procedure is fairly sensitive to the independent
      measurement error assumption. To overcome this limitation, we propose new
      estimation procedures that require neither a distributional or covariance
      structural assumption on covariate random effects nor an independence assumption
      on within-subject measurement errors. These new procedures are more flexible,
      readily cover scenarios that have multivariate longitudinal covariate processes,
      and can be implemented using available software. Through simulations and an
      analysis of data from a hypertension study, we evaluate and illustrate the
      numerical performances of the new estimators.

PMID- 17501941
TI  - A bayesian approach to the multistate Jolly-Seber capture-recapture model.
AB  - This article considers a Bayesian approach to the multistate extension of the
      Jolly-Seber model commonly used to estimate population abundance in capture
      recapture studies. It extends the work of George and Robert (1992, Biometrika79,
      677-683), which dealt with the Bayesian estimation of a closed population with
      only a single state for all animals. A super-population is introduced to model
      new entrants in the population. Bayesian estimates of abundance are obtained by
      implementing a Gibbs sampling algorithm based on data augmentation of the missing
      data in the capture histories when the state of the animal is unknown. Moreover,
      a partitioning of the missing data is adopted to ensure the convergence of the
      Gibbs sampling algorithm even in the presence of impossible transitions between
      some states. Lastly, we apply our methodology to a population of fish to estimate
      abundance and movement.

PMID- 17501942
TI  - A conservative test for multiple comparison based on highly correlated test
      statistics.
AB  - In genetics, we often encounter a large number of highly correlated test
      statistics. The most famous conservative bound for multiple comparison is
      Bonferroni's bound, which is suitable when the test statistics are independent
      but not when the test statistics are highly correlated. This article proposes a
      new conservative bound that is easily calculated without multiple integration and
      is a good approximation when the test statistics are highly correlated. The
      performance of the proposed method is evaluated by simulation and real data
      analysis.

PMID- 17501943
TI  - Nonparametric bayesian estimation of positive false discovery rates.
AB  - We propose a Dirichlet process mixture model (DPMM) for the P-value distribution
      in a multiple testing problem. The DPMM allows us to obtain posterior estimates
      of quantities such as the proportion of true null hypothesis and the probability
      of rejection of a single hypothesis. We describe a Markov chain Monte Carlo
      algorithm for computing the posterior and the posterior estimates. We propose an
      estimator of the positive false discovery rate based on these posterior estimates
      and investigate the performance of the proposed estimator via simulation. We also
      apply our methodology to analyze a leukemia data set.

PMID- 17501944
TI  - Just-identified versus overidentified two-level hierarchical linear models with
      missing data.
AB  - The development of model-based methods for incomplete data has been a seminal
      contribution to statistical practice. Under the assumption of ignorable
      missingness, one estimates the joint distribution of the complete data for
      thetainTheta from the incomplete or observed data y(obs). Many interesting models
      involve one-to-one transformations of theta. For example, with y(i) approximately
      N(mu, Sigma) for i= 1, ... , n and theta= (mu, Sigma), an ordinary least squares
      (OLS) regression model is a one-to-one transformation of theta. Inferences based
      on such a transformation are equivalent to inferences based on OLS using data
      multiply imputed from f(y(mis) | y(obs), theta) for missing y(mis). Thus,
      identification of theta from y(obs) is equivalent to identification of the
      regression model. In this article, we consider a model for two-level data with
      continuous outcomes where the observations within each cluster are dependent. The
      parameters of the hierarchical linear model (HLM) of interest, however, lie in a
      subspace of Theta in general. This identification of the joint distribution
      overidentifies the HLM. We show how to characterize the joint distribution so
      that its parameters are a one-to-one transformation of the parameters of the HLM.
      This leads to efficient estimation of the HLM from incomplete data using either
      the transformation method or the method of multiple imputation. The approach
      allows outcomes and covariates to be missing at either of the two levels, and the
      HLM of interest can involve the regression of any subset of variables on a
      disjoint subset of variables conceived as covariates.

PMID- 17501945
TI  - On smoothing trends in population index modeling.
AB  - In this article, we consider the U.K. Common Birds Census counts and their use in
      monitoring bird abundance. We use a state-space modeling approach within a
      Bayesian framework to describe population level trends over time and contribute
      to the alert system used by the British Trust for Ornithology. We account for
      potential overdispersion and excess zero counts by modeling the observation
      process with a zero-inflated negative binomial, while the system process is
      described by second-order polynomial growth models. In order to provide a
      biological motivation for the amount of smoothing applied to the observed series
      the system variance is related to the demographic characteristics of the species,
      so as to help the specification of its prior distribution. In particular, the
      available information on productivity and survival is used to formulate prior
      expectations on annual percentage changes in the population level and then used
      to constrain the variance of the system process. We discuss an example of how to
      interpret alternative choices for the degree of smoothing and how these relate to
      the classification of species, over time, into conservation lists.

PMID- 17501946
TI  - Comparison of group testing algorithms for case identification in the presence of
      test error.
AB  - We derive and compare the operating characteristics of hierarchical and square
      array-based testing algorithms for case identification in the presence of testing
      error. The operating characteristics investigated include efficiency (i.e.,
      expected number of tests per specimen) and error rates (i.e., sensitivity,
      specificity, positive and negative predictive values, per-family error rate, and
      per-comparison error rate). The methodology is illustrated by comparing different
      pooling algorithms for the detection of individuals recently infected with HIV in
      North Carolina and Malawi.

PMID- 17501947
TI  - Neonatal follicular mucinosis.

PMID- 17501948
TI  - Novel COL7A1 mutations in a Japanese family with transient bullous dermolysis of
      the newborn associated with pseudosyndactyly.

PMID- 17501949
TI  - Cutaneous Mycobacterium neoaurum infection causing scarring alopecia in an
      immunocompetent host.

PMID- 17501950
TI  - The use of intravenous immunoglobulin in cutaneous and recurrent perforating
      intestinal Degos disease (malignant atrophic papulosis).

PMID- 17501952
TI  - A novel deletion mutation in the EDAR gene in a Pakistani family with autosomal
      recessive hypohidrotic ectodermal dysplasia.

PMID- 17501951
TI  - Corticosteroid-induced clinical adverse events: frequency, risk factors and
      patient's opinion.
AB  - BACKGROUND: More than 50 years after the introduction of corticosteroids, few
      studies have focused on corticosteroid-induced adverse events after long-term
      systemic therapy. OBJECTIVES: To assess the frequency, risk factors and patient's
      opinion regarding clinical adverse events occurring early during prednisone
      therapy. PATIENTS AND METHODS: We conducted a cohort study in two French centres.
      All consecutive patients starting long-term (> oir = 3 months), high dosage (> or
      = 20 mg day(-1)) prednisone therapy were enrolled. The main clinical adverse
      events attributable to corticosteroids were assessed after 3 months of therapy,
      by comparison with baseline status. The patient's opinion regarding the
      disability induced by these adverse events was recorded. Risk factors of
      frequently observed adverse effects were identified by using logistic regression.
      RESULTS: Eighty-eight patients were enrolled and 80 were monitored for at least 3
      months (women 76%; mean age 59.1 +/- 18.7 years; giant cell arteritis 39%; mean
      baseline prednisone dosage 54 +/- 17 mg day(-1)). Lipodystrophy was the most
      frequent adverse event [63.0% (51.0-73.1)], was considered the most distressing
      by the patients and was most frequent in women and young patients.
      Neuropsychiatric disorders occurred in 42 patients [52.5% (41.0-63.8)],
      necessitating hospitalization in five cases. Skin disorders were noted by 37
      patients [46.2% (35.0-57.7)] and were more frequent in women. Muscle cramp and
      proximal muscle weakness were reported by 32.5% (22.5-43.9) and 15% (8.0-24.7) of
      patients, respectively. Newly developed hypertension occurred in 8.7% (2.9-20.3)
      of patients. Lastly, 39% (19.7-61.4) of the premenopausal women reported
      menstrual disorders. CONCLUSIONS: Lipodystrophy and neuropsychiatric disorders
      are common adverse events of long-term prednisone therapy and are particularly
      distressing for the patients concerned. The impact of these adverse events on
      adherence to corticosteroid therapy is not known.

PMID- 17501953
TI  - Mondor's phlebitis after using tadalafil.

PMID- 17501954
TI  - Randomized, double-blind, prospective study to compare topical 5-aminolaevulinic
      acid methylester with topical 5-aminolaevulinic acid photodynamic therapy for
      extensive scalp actinic keratosis.
AB  - BACKGROUND: 5-aminolaevlinic acid methylester (MAL) and 5-aminolaevulinic acid
      (ALA) photodynamic therapy (PDT) are both effective treatment options for actinic
      keratosis (AK). While MAL is significantly more expensive than ALA, no studies
      have directly compared their efficacy in the treatment of extensive scalp AK.
      OBJECTIVES: To compare the efficacy and adverse effects of MAL-PDT with ALA-PDT
      in the treatment of scalp AK. METHODS: Sixteen male patients aged 59-87 years
      with extensive scalp AK were randomized into a double-blind, split-scalp
      prospective study. Two treatment fields were defined (right and left
      frontoparietal scalp) and treated 2 weeks apart. These fields were randomized to
      receive either MAL or ALA as first or second treatment. MAL cream was applied for
      3 h; 20% ALA cream was applied for 5 h. A blinded observer assessed efficacy
      comparing AK counts before and 1 month after treatment. Pain was assessed using a
      visual analogue scale at 3, 6, 12 and 16 min. RESULTS: Fifteen patients completed
      treatment to both fields. There was a mean reduction from baseline in AK counts
      with the use of ALA-PDT of 6.2 +/- 1.9 compared with 5.6 +/- 3.2 with MAL-PDT (P
      = 0.588). All patients experienced pain which was of greater intensity in the ALA
      treated side at all time points: 3 min (P = 0.151), 6 min (P = 0.085), 12 min (P
      = 0.012) and 16 min (P = 0.029). Similarly, duration of discomfort post-procedure
      persisted for longer following treatment with ALA when compared with MAL-PDT (P =
      0.044). CONCLUSIONS: This study demonstrates that both ALA-PDT and MAL-PDT result
      in a significant reduction in scalp AK. There is no significant difference in
      efficacy. However, ALA-PDT is more painful than MAL-PDT in the treatment of
      extensive scalp AK.

PMID- 17501955
TI  - Vehicle-controlled, randomized, double-blind study to assess safety and efficacy
      of imiquimod 5% cream applied once daily 3 days per week in one or two courses of
      treatment of actinic keratoses on the head.
AB  - BACKGROUND: Imiquimod has been investigated as a safe and effective therapeutic
      option for the treatment of actinic keratosis (AK). OBJECTIVES: To evaluate
      imiquimod vs. vehicle applied three times a week for 4 weeks in one or two
      courses of treatment for AK on the face or balding scalp. PATIENTS AND METHODS:
      Patients diagnosed with AK were enrolled in this multicentre, vehicle-controlled,
      double-blind study conducted in Europe. Twenty study centres enrolled a total of
      259 patients in this study. Patients applied the study drug for 4 weeks, entered
      a 4-week rest period and if they did not have complete clearance, they then
      entered a second course of treatment. RESULTS: Patients in the imiquimod group
      had an overall complete clearance rate of 55.0% (71/129) vs. a rate of 2.3%
      (3/130) for the vehicle group. There was a high rate of agreement between the
      clinical assessment and histological findings with respect to AK lesion
      clearance. At both 8-week post-treatment visits, the negative predictive value of
      the investigator assessment was 92.2% for clinical assessments vs. histological
      results. CONCLUSIONS: A 4-week course of treatment with three times weekly dosing
      of imiquimod 5% cream, with a repeated course of treatment for those patients who
      fail to clear after the first course of treatment, is a safe and effective
      treatment for AK. The overall complete clearance rate (complete clearance after
      either course 1 or course 2) is comparable to the 16-week treatment regimen,
      while decreasing drug exposure to the patient and decreasing the overall
      treatment time.

PMID- 17501956
TI  - Efficacy and tolerability of a Chinese herbal medicine concoction for treatment
      of atopic dermatitis: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: There has been considerable interest in traditional Chinese herbal
      medicine (TCHM) as a treatment for atopic dermatitis (AD). A twice-daily
      concoction of an ancestral formula containing five herbs has been found to be
      beneficial in an open study. OBJECTIVES: To assess the efficacy and tolerability
      of the concoction in children with AD. METHODS: Following a 2-week run-in period,
      children with long-standing moderate-to-severe AD were randomized to receive a 12
      week treatment with twice-daily dosing of three capsules of either TCHM or
      placebo. The SCORing of Atopic Dermatitis (SCORAD) score, Children's Dermatology
      Life Quality Index (CDLQI), allergic rhinitis score, and requirement for topical
      corticosteroid and oral antihistamine were assessed before and at weeks 4, 8, 12
      and 16 after treatment. Adverse events, tolerability, haematological and
      biochemical parameters were monitored during the study. RESULTS: Eighty-five
      children with AD were recruited. Over 12 weeks, the mean SCORAD score fell from
      58.3 to 49.7 in the TCHM group (n = 42; P = 0.003) and from 56.9 to 46.9 in the
      placebo group (n = 43; P = 0.001). However, there was no significant difference
      in the scores at the corresponding time points between the two groups. The CDLQI
      in TCHM-treated patients was significantly improved compared with patients
      receiving placebo at the end of the 3-month treatment and 4 weeks after stopping
      therapy (P = 0.008 and 0.059, respectively). The total amount of topical
      corticosteroid used was also significantly reduced by one-third in the TCHM group
      (P = 0.024). No serious adverse effects were observed between the groups.
      CONCLUSIONS: The TCHM concoction is efficacious in improving quality of life and
      reducing topical corticosteroid use in children with moderate-to-severe AD. The
      formulation was palatable and well tolerated.

PMID- 17501957
TI  - Sentinel lymph node biopsy in melanoma: a micromorphometric study relating to
      prognosis and completion lymph node dissection.
AB  - BACKGROUND: Sentinel lymph node (SLN) positivity has been found to be strongly
      associated with a poor prognosis in melanoma. OBJECTIVES: This large referral
      centre study was conducted: (i) to confirm the powerful prognostic value of SLN
      biopsy (SLNB); (ii) to correlate patient prognosis to the micromorphometric
      features of SLN metastasis in SLN-positive patients; and (iii) to correlate these
      micromorphometric features to the likelihood of positive completion lymph node
      dissection (CLND). PATIENTS AND METHODS: SLNB was performed in 455 cases of
      primary melanoma between January 1999 and December 2004; for patients with
      positive SLN, the following micromorphometric features were registered: size of
      the largest metastasis (two diameters), depth of metastasis, number of
      millimetric slices involved, maximum number of metastases on a single section,
      presence of intracapsular lymphatic invasion and extracapsular spread. Kaplan
      Meier survival curves were compared with the log-rank test; multivariate analysis
      was performed using a Cox regression model. Dependence of CLND status on
      micromorphometric features of SLN was assessed by the chi(2) test and predictive
      values of the different features were evaluated by multivariate analysis using a
      logistic regression model. RESULTS: A positive SLN was identified in 98 of our
      455 cases. Survival was significantly shorter in SLN-positive patients than in
      SLN-negative patients. Extracapsular invasion was found to be an independent
      prognostic factor of disease-free survival; ulceration of the primary and the
      maximum diameter of the largest metastasis were identified as independent
      predictive factors of disease-specific survival. Age and the lowest diameter of
      the largest metastasis were identified as independent predictive criteria of
      positive CLND, whereas depth of metastasis was not. Positivity of CLND was not
      significantly associated with a worse prognosis. CONCLUSIONS: Our study confirms
      the previously demonstrated strong prognostic value of SLNB. It also confirms the
      relationship between tumour burden in the SLN (evaluated by the maximum diameter
      of the largest metastasis) and clinical outcome. We point out a new
      micromorphometric feature of SLN, which seems to be predictive of CLND status:
      the lowest diameter of the largest metastasis.

PMID- 17501958
TI  - Surgical outcome and long-term follow up after laparoscopic rectosigmoid
      resection in women with deep infiltrating endometriosis.
AB  - The aim of this study was to assess the long-term outcome of treating severely
      symptomatic women with deep infiltrating intestinal endometriosis by laparoscopic
      segmental rectosigmoid resection. Detailed intraoperative and postoperative
      records and questionnaires (preoperatively, 1 month postoperatively and every 6
      months for 3 years) were collected from 22 women. The estimated blood loss during
      surgery was 290 +/- 162 ml (range 180-600), and average hospital stay was 8 days
      (range 6-19). One woman required blood transfusion after surgery. Two cases were
      converted to laparotomy. One woman had early dehiscence of the anastomosis. Six
      months after surgery, there was a significant reduction of symptom scores
      (greater than 50% for most types of pain) related to intestinal localisation of
      endometriosis (P < 0.05). Score improvements were maintained during the whole
      period of follow up. Noncyclic pelvic pain scores showed significant reductions
      (P < 0.05) after 6 and 12 months, but there was a high recurrence rate later.
      Dysmenorrhoea and dyspareunia improved in 18/21 and 14/18 women with preoperative
      symptoms, respectively. Constipation, diarrhoea and rectal bleeding improved in
      all affected women for the whole period of follow up. Laparoscopic segmental
      rectosigmoid resection seems safe and effective in women with deep infiltrating
      colorectal endometriosis resulting in significant reductions in painful and
      dysfunctional symptoms associated with deep bowel involvement.

PMID- 17501959
TI  - Pregnancy outcomes and antiretroviral treatment in a national cohort of pregnant
      women with HIV: overall rates and differences according to nationality.
AB  - We used data from the main surveillance study of HIV and pregnancy in Italy to
      evaluate possible differences in pregnancy care and outcomes according to
      nationality. Among 960 women followed in 2001-06, 33.5% were of foreign
      nationality, mostly from African countries. Foreign women had lower rates of
      preconception counselling and planning of pregnancy. They had more frequently HIV
      diagnosed during pregnancy, with a later start of antiretroviral treatment and
      lower treatment rates at all trimesters but not when the entire pregnancy,
      including delivery, was considered. No differences were observed between the two
      groups in ultrasonography assessments, hospitalisations, AIDS events,
      intrauterine or neonatal deaths, and mode and complications of delivery. Foreign
      women had a slightly lower occurrence of preterm delivery and infants with low
      birthweight. The results indicate good standards of care and low rates of adverse
      outcomes in pregnant women with HIV in Italy, irrespective of nationality.
      Specific interventions, however, are needed to increase the rates of counselling
      and HIV testing before pregnancy in foreign women.

PMID- 17501960
TI  - Follow up and evaluation of the Victorian first-trimester combined screening
      programme for Down syndrome and trisomy 18.
AB  - OBJECTIVE: The objective of this study was to follow up and evaluate the
      statewide first-trimester combined screening programme for Down syndrome and
      trisomy 18 at Genetic Health Services Victoria, Australia. DESIGN: Retrospective
      population cohort. SETTING: Maternal Serum Screening Laboratory records. SAMPLE:
      All women screened between February 2000 and June 2002 (16,153 pregnancies).
      METHODS: Screening results were matched to Victorian perinatal and birth defect
      data via record linkage, with an ascertainment of 96.8% of pregnancy outcomes.
      Manual follow up with health professionals increased ascertainment to more than
      99%. MAIN OUTCOME MEASURES: Fetal Down syndrome or trisomy 18, and combined
      screen results, to calculate test characteristics. RESULTS: Using a risk
      threshold of 1 in 300 at time of ultrasound, the sensitivities for standard first
      trimester combined screening and augmented 13-week combined screening for Down
      syndrome were 87.3 and 90.5% and the false-positive rates (FPR) were 4.1 and
      3.9%, respectively. The sensitivity for trisomy 18 was 66.7% (10/15, 95% CI 42.8
      90.5%) with a 0.4% FPR and 15.2% positive predictive value (1 in 250 risk
      threshold). CONCLUSIONS: The combined use of record linkage and manual follow-up
      techniques was effective in ascertaining more than 99% of pregnancy outcomes for
      calculations of accurate test characteristics of the combined screen. The
      sensitivity for Down syndrome at Genetic Health is comparable to similar
      populations. However, the sensitivity for trisomy 18 is lower than that
      elsewhere, which may reflect the overall low birth prevalence of trisomy 18 and
      associated small numbers in this particular cohort.

PMID- 17501961
TI  - Direct imaging of the pelvic floor muscles using two-dimensional ultrasound: a
      comparison of women with urogenital prolapse versus controls.
AB  - OBJECTIVE: To evaluate the anatomy of the levator ani muscle in women with
      urogenital prolapse versus matched controls without prolapse using real-time two
      dimensional (2-D) ultrasound. DESIGN: Prospective observational study. SETTING:
      Tertiary referral urogynaecology unit. POPULATION: Forty-three women with pelvic
      organ prolapse (POP) and 24 women (controls) attending a gynaecology clinic
      without prolapse. METHODS: All participants completed a standardised symptom
      questionnaire. MAIN OUTCOME MEASURES: The morphology of the vagina and
      paravaginal tissue was recorded at different levels. The thickness of the levator
      ani and the hiatal area were measured at rest. Reproducibility of the method was
      assessed by repeated measurements to assess intra-observer variability and inter
      observer variability. RESULTS: This method showed good intra-observer and inter
      observer reproducibility and reliability. In controls, the pubococcygeus muscle
      showed more regular echogenicity with no evidence of trauma, whereas in women
      with prolapse the muscle had mixed echogenicity. (P = 0.002). The mean thickness
      of the pubococcygeus did not differ between groups. The levator hiatal area was
      significantly larger in women with pelvic floor prolapse versus controls (17.8
      cm2 versus 13.5 cm2, P < 0.001). This increase in hiatal area positively and
      significantly correlated with prolapse severity (P < 0.001). CONCLUSIONS:
      Morphology and hiatal area can be reliably imaged using 2-D ultrasound. Prolapse
      was related to changes in pelvic floor morphology and increased levator hiatal
      area. The use of 2-D ultrasound provides an important insight into the
      pathophysiology of prolapse.

PMID- 17501962
TI  - Trends in mode of delivery during 1984-2003: can they be explained by pregnancy
      and delivery complications?
AB  - OBJECTIVES: To describe trends in mode of delivery, to identify significant
      factors which affected mode of delivery, and to describe how these factors and
      their impact have changed over time. DESIGN: Total population birth cohort.
      SETTING: Western Australia 1984-2003. PARTICIPANTS: The analysis was restricted
      to all singleton infants delivered at 37-42 weeks of gestation with a cephalic
      presentation (n = 432,327). METHODS: Logistic regression analyses were undertaken
      to estimate significant independent risk factors separately for elective and
      emergency caesarean sections compared with vaginal delivery (spontaneous and
      instrumental), adjusting for potential confounding variables. MAIN OUTCOME
      MEASURES: Trends in mode of delivery, demographic factors, and pregnancy and
      delivery complications. Estimated likelihood of elective caesarean section
      compared with vaginal delivery and emergency caesarean section compared with
      vaginal delivery. RESULTS: Between 1984-88 and 1999-2003, the likelihood of women
      having an elective caesarean section increased by a factor of 2.35 times (95% CI
      2.28-2.42) and the likelihood of an emergency caesarean section increased 1.89
      times (95% CI 1.83-1.96). These caesarean section rate increases remained even
      after adjustment for their strong associations with many sociodemographic
      factors, obstetric risk factors, and obstetric complications. Rates of caesarean
      section were higher in older mothers, especially those older than 40 years of age
      (elective caesarean section, OR 5.42 [95% CI 4.88-6.01]; emergency caesarean
      section, OR 2.67 [95% CI 2.39-2.97]), and in nulliparous women (elective
      caesarean section, OR 1.54 [95% CI 1.47-1.61]; emergency caesarean section, OR
      3.61 [95% CI 3.47-3.76]). CONCLUSIONS: Our data show significant changes in mode
      of delivery in Western Australia from 1984-2003, with an increasing trend in both
      elective and emergency caesarean section rates that do not appear to be explained
      by increased risk or indication.

PMID- 17501964
TI  - Urethral pressure reflectometry vs urethral pressure profilometry in women: a
      comparative study of reproducibility and accuracy.
AB  - OBJECTIVE: To compare urethral pressure reflectometry (UPR), a new and simple
      technique for simultaneous measurements of cross-sectional area (CA) and pressure
      in the female urethra, with urethral pressure profilometry (UPP). PATIENTS,
      SUBJECTS AND METHODS: The study included 143 women (105 patients and 38 healthy
      volunteers); the UPR was measured using a very thin polyurethane bag in the
      urethra; a pump applied pre-selected pressures stepwise to the bag and for each
      step the CA was measured by acoustic reflectometry. Measurements were made during
      both inflation and deflation. The women were examined supine both while relaxed
      and during 'squeeze', and while upright and relaxed. The following variables were
      measured; the opening and closing pressure, the opening and closing elastance and
      the hysteresis. For UPP we used the perfusion technique with the patient supine
      and relaxed. All the women were assessed twice with both UPR and UPP at the same
      setting (short-term reproducibility) and 17 patients were assessed with both
      methods on two different days (long-term reproducibility). RESULTS: The mean
      pressures were 51.7 and 52.9 cmH(2)O for the UPR and UPP, respectively (not
      significant) at a CA of 5.1 mm(2); the limit of agreement between the methods was
      -19.4 to +17.0 cmH(2)O (mean and 2 SD). The Pearson coefficient was - 0.16 (not
      significant). The variability (2 sd) of two consecutive measurements was
      significantly less with UPR (9.5 cmH(2)O) than UPP (13.8 cmH(2)O; P < 0.001). For
      the opening and closing pressures the coefficient of variation (CV) was 5.9
      11.6%; for the elastances the CV was 14.3-31.2% and for the hysteresis the CV was
      12.9-49.1%. In test-retest measurements, the variability of the UPR values (2 sd,
      8.7 cmH(2)O) was significantly less than for UPP (15.4 cmH(2)O; P < 0.05). The
      discomfort of UPR was statistically less than for UPP or than a standard
      gynaecological examination. CONCLUSION: Compared at the same CA, UPR measured the
      same pressure as UPP but the UPR was more reproducible. With the patient relaxed
      the opening and closing pressure, opening and closing elastance and the
      hysteresis can be measured while supine and upright; while squeezing, the opening
      pressure and elastance can be measured.

PMID- 17501963
TI  - Limitations of ST analysis in clinical practice: three cases of intrapartum
      metabolic acidosis.
AB  - OBJECTIVE: To examine detailed intrapartum events in cases of neonatal metabolic
      acidosis despite monitoring using STAN (cardiotocography [CTG] plus ST waveform
      analysis of fetal electrocardiogram [ECG]). DESIGN: Retrospective case review.
      SETTING: High-risk pregnancies monitored by STAN. METHODS: Case note review was
      performed in newborns with metabolic acidosis where no significant ST changes in
      the fetal ECG occurred prior to birth. MAIN OUTCOME MEASURES: Metabolic acidosis.
      RESULTS: Detailed review of three cases identified poor signal quality,
      difficulties in CTG interpretation, failure to comply with STAN clinical
      guidelines and deterioration of the CTG without ECG alert as the leading causes
      of these adverse outcomes. CONCLUSIONS: The cases illustrate some of the pitfalls
      associated with the clinical application of the STAN technology which prevent
      severe metabolic acidosis being eradicated completely. It may be useful to expand
      the STAN guidelines protocol towards the identification of exceptional clinical
      situations, such as in our cases, and towards appropriate additional
      interventions, as this may lead to a further reduction in adverse neonatal
      outcomes.

PMID- 17501965
TI  - Isolated lip involvement in psoriasis.

PMID- 17501966
TI  - An erythematous nodule on the eyelid.

PMID- 17501967
TI  - A facial tumour.

PMID- 17501968
TI  - Chronically painful right thumb with pustules and onycholysis. Diagnosis:
      acrodermatitis continua of Hallopeau.

PMID- 17501969
TI  - A cerebellar demyelinating lesion following treatment of acne with isotretinoin.
AB  - We report the case of a demyelinating lesion located in the left cerebellar
      region that developed 3 months after the onset of oral isotretinoin treatment. In
      April 2001, 1 year before admission, the patient underwent cranial magnetic
      resonance imaging (MRI) because of endocrinological problems. This was found to
      be completely normal. In January 2002, oral isotretinoin treatment was started to
      treat severe acne. Three months after the onset of therapy, the patient reported
      lack of appetite, faintness and tinnitus. Her second cranial MRI scan showed a
      cerebellar lesion, and oral isotretinoin treatment was stopped (April 2002). One
      month after the cessation of oral isotretinoin treatment, the lesion became less
      prominent on the MRI scan, and after 3 months, it had disappeared. Although it is
      difficult to determine the causal association between the demyelinating
      cerebellar lesion and isotretinoin treatment, we would like to alert physicians
      to this possibility, because of the common usage of this drug in daily practice.

PMID- 17501970
TI  - A florid skin rash in a returning traveller.

PMID- 17501972
TI  - More evidence is required for short-term treatment of exacerbations of chronic
      obstructive pulmonary disease: 3 days or no antibiotic at all?

PMID- 17501973
TI  - Characteristics and regional variations of group D streptococcal endocarditis in
      France.
AB  - The proportion of infective endocarditis (IE) caused by group D streptococci
      (GDS; formerly Streptococcus bovis) increased markedly in France, to account for
      25% of all cases of IE by 1999. In an attempt to explain this phenomenon, a
      comparative analysis of GDS and oral streptococci (OS) causing IE was performed.
      This study was based on data collected from a large cross-sectional population
      based survey that was conducted in 1999. In total, 559 cases of definite IE were
      recorded, of which 142 involved GDS and 79 involved OS. Patients with GDS IE were
      older (62.7 vs. 56.6 years, p 0.01) and had a history of valve disease less
      frequently than did patients with OS IE (33.8% vs. 67.1%, p <0.0001). At-risk
      procedures for IE were performed less frequently in patients with GDS than in
      patients with OS (14.8% vs. 24.1%, p 0.08), but co-morbidities were more frequent
      in the GDS group (59.9% vs. 32.9%, p 0.0001). Diabetes, colon diseases and
      cirrhosis were also more frequent in the GDS group (p 0.006, p <0.0001 and p
      0.08, respectively). Rural residents accounted for 31.0% of the GDS group, but
      for only 15.2% of the OS group (p 0.001). Likewise, the proportion of GDS IE was
      higher in regions with mixed (urban and rural) populations (Franche-Comte 81.8%,
      Marne 68.7%, Lorraine 70.3% and Rhone-Alpes 65.3%) than in exclusively urban
      regions (Paris and Ile de France 58.0%). Further investigations are required to
      elucidate the link in France between the incidence of GDS IE, rural residency and
      nutritional factors.

PMID- 17501974
TI  - Analysis of the role of Mycobacterium tuberculosis kasA gene mutations in
      isoniazid resistance.
AB  - Previous studies have suggested that Mycobacterium tuberculosis kasA G312S and
      G269S gene mutations may represent sequence polymorphisms of the M. tuberculosis
      East-African-Indian (EAI) and T families, respectively, rather than relating to
      isoniazid resistance. The present study examined polymorphisms of these two
      codons in 98 drug-susceptible M. tuberculosis isolates (68 EAI and 30 T
      isolates). Twenty-eight isolates belonging to a sub-lineage of the EAI family had
      the kasA G312S mutation, but none of the 30 T isolates had the G269S mutation.
      The data suggest that the kasA G312S mutation is not related to isoniazid
      resistance, but represents a sequence polymorphism in a sub-lineage of the EAI
      family.

PMID- 17501975
TI  - Gentamicin susceptibility in Escherichia coli related to the genetic background:
      problems with breakpoints.
AB  - In total, 120 Escherichia coli isolates positive for one of the gentamicin
      resistance (GEN(R)) genes aac(3)-II, aac(3)-IV or ant(2'')-I were tested for
      gentamicin susceptibility by the agar dilution method. Isolates positive for
      aac(3)-IV or ant(2'')-I had an MIC distribution of 8-64 mg/L, whereas isolates
      positive for aac(3)-II had MICs of 32 to >512 mg/L, suggesting a relationship
      between the distribution of MICs and the specific GEN(R) mechanism. The MIC
      distribution, regardless of the GEN(R) mechanism, was 8 - >512 mg/L, which
      supports the clinical breakpoint of MIC >4 mg/L suggested by EUCAST and questions
      the breakpoint recommended by the CLSI (> or =16 mg/L).

PMID- 17501976
TI  - Feasibility of commercial interferon-gamma-based methods for the diagnosis of
      latent Mycobacterium tuberculosis infection in Finland, a country of low
      incidence and high bacille Calmette-Guerin vaccination coverage.
AB  - The performances of the QuantiFERON-TB Gold in Tubes (QFGT), T SPOT-TB (ELISPOT)
      and the Mantoux test were compared for the diagnosis of latent tuberculosis
      infection in Finland, a country of low tuberculosis incidence. In Cohort A (16
      students), freshly isolated peripheral blood mononuclear cells (PBMCs), and in
      Cohort B (21 school children), cryopreserved PBMCs, were used for the ELISPOT
      assay. Cryopreservation of cells in fetal calf serum, but not in serum-free
      medium, produced false-positive results. Discrepancies between the results of the
      assays were observed. It was concluded that the accuracy of these ex-vivo methods
      needs additional evaluation.

PMID- 17501977
TI  - Distribution and expression of macrolide resistance genes in coagulase-negative
      staphylococci.
AB  - In total, 494 isolates of coagulase-negative staphylococci (CoNS) were identified
      to the species level by biochemical tests and sodA sequencing. Erythromycin
      resistance phenotypes were determined and specific resistance genes were
      identified by PCR. The prevalence of erythromycin resistance varied widely among
      staphylococcal species, from 0% in Staphylococcus lugdunensis to almost 90% in
      Staphylococcus haemolyticus. Most (63%) erythromycin-resistant isolates carried
      constitutively expressed erm(C) as the sole resistance determinant, with the
      notable exception of Staphylococcus hominis subsp. hominis, which carried
      inducible erm(C). The erm(A) and erm(B) determinants were comparatively rare. The
      msr(A) gene was carried by 20-30% of all erythromycin-resistant isolates, with
      little variation among species, and was combined in 16.7% of isolates with
      mph(C), a resistance gene of unknown clinical relevance found previously in
      isolates of veterinary origin. No erythromycin resistance that could not be
      attributed to the genes investigated was detected. It was concluded that the
      presence of methylases cannot be assumed in CoNS isolates that appear
      erythromycin-resistant and clindamycin-susceptible; thus, methods that detect the
      export mechanism should be used with clinically significant isolates to indicate
      whether use of clindamycin may be effective. In Staphylococcus epidermidis and S.
      haemolyticus, 46% and 66%, respectively, of erythromycin-resistant, clindamycin
      susceptible isolates were susceptible to clindamycin therapy.

PMID- 17501978
TI  - Bacterial colonization immediately after installation on oral titanium implants.
AB  - BACKGROUND: Information on bacterial colonization immediately after dental
      implant insertion is limited. AIMS: (1) To assess the early colonization on
      titanium implants immediately after placement and throughout the first 12 post
      surgical weeks, (2) to compare the microbiota at interproximal subgingival
      implant and adjacent tooth sites. MATERIAL AND METHODS: Subgingival plaque
      samples from implant and neighbouring teeth were studied by checkerboard DNA-DNA
      hybridization before surgery, 30 min after implant placement, and 1, 2, 4, 8, and
      12 weeks after surgery. RESULTS: Comparing bacterial loads at implant sites
      between 30 min after placement with 1-week data showed that only the levels of
      Veillonella parvula (P<0.05) differed with higher loads at week 1 post
      surgically. Week 12 data demonstrated significantly higher bacterial loads for
      15/40 species at tooth sites compared with pre-surgery (P-values varying between
      0.05 and 0.01). Between the period immediately after surgery and 12 weeks at
      implant sites, 29/40 species was more commonly found at 12 weeks. Included among
      these bacteria at implant sites were Porphyromonas gingivalis (P<0.05),
      Tannerella forsythia, (P<0.01), and Treponema denticola (P<0.001). Immediately
      post-surgery 5.9% of implants, and 26.2% of teeth, and at week 12, 15% of
      implants, and 39.1% of teeth harbored Staphylococcus aureus. Comparing tooth and
      implant sites, significantly higher bacterial loads were found at tooth sites for
      27/40 species after 30 min following implant placement. This difference increased
      to 35/40 species at 12 weeks post-surgically. CONCLUSIONS: Bacterial colonization
      occurred within 30 min after implant placement. Early colonization patterns
      differed between implant and tooth surfaces.

PMID- 17501979
TI  - Autogenous onlay bone grafts vs. alveolar distraction osteogenesis for the
      correction of vertically deficient edentulous ridges: a 2-4-year prospective
      study on humans.
AB  - OBJECTIVES: The purposes of this study were to compare: (a) autogenous bone
      grafts (ABG) and distraction osteogenesis (DO) for their ability in correcting
      vertically deficient mandibular ridges and their capability in maintaining over
      time the vertical bone gain obtained before and after implant placement; and (b)
      the survival and success rates of implants placed in the reconstructed or
      distracted areas. MATERIAL AND METHODS: In a 2-year period (2001-2002), 17
      patients presenting with vertically atrophied partially edentulous mandibles
      requiring implant-supported prosthetic rehabilitation, were included in this
      study. Patients were randomly assigned to two groups. Eight patients (group 1)
      were treated with ABG harvested from the mandibular ramus, while nine patients
      (group 2) were treated by means of DO. In group 1, patients received implants 4-5
      months after the reconstructive procedure, while in group 2 implants were placed
      at the time of distraction device removal (approximately 3 months after the
      completion of distraction). A total of 19 endosseous implants were placed in
      group 1, and 21 implants were placed in group 2 patients. For both groups, after
      an additional 3-5-month period, prosthetic rehabilitation was started. RESULTS:
      Bone resorption before implant placement was significantly higher in group 1
      (P=0.01), while no statistically significant differences were found between the
      two groups as far as survival and success rates of implants and peri-implant bone
      resorption after the start of prosthetic loading were concerned. CONCLUSION: The
      results suggested that: (a) both techniques may effectively improve the deficit
      of vertically resorbed edentulous ridges; (b) survival and success rates of
      implants placed in the reconstructed/distracted areas are consistent with those
      of implants placed in native bone.

PMID- 17501980
TI  - Direct loading of Nobel Direct and Nobel Perfect one-piece implants: a 1-year
      prospective clinical and radiographic study.
AB  - OBJECTIVES: The aim of this prospective study was to evaluate the Nobel Direct
      and Nobel Perfect one-piece implants (OPIs) when used for immediate function.
      MATERIAL AND METHODS: Forty-eight patients were provided with 115 OPIs for
      loading with a provisional crown or a bridge within 24 h and followed for at
      least 12 months with clinical and radiographic examinations. A group of 97
      patients previously treated under identical conditions by the same team with 380
      two-piece implants (TPIs) for immediate loading in the mandible and maxilla
      served as the reference group. RESULTS: Six (5.2%) OPIs failed during the follow
      up due to extensive bone loss. Five (1.3%) implants failed in the reference
      group. After 1 year, the mean marginal bone loss was 2.1 mm (SD 1.3) for OPIs and
      0.8 mm (SD 1) for TPIs. 20% of OPIs showed more than 3 mm of bone loss compared
      with 0.6% for TPIs. When compensating for vertical placement depth, OPIs still
      showed a lower marginal bone level and thus more exposed threads than TPIs.
      Depending on the criteria used, the success rate for OPIs was 46.1% or 72.2%
      compared with 85% or 91.6% for TPIs. CONCLUSIONS: The Nobel Direct and Nobel
      Perfect OPIs show lower success rates and more bone resorption than TPIs after 1
      year in function. Factors such as implant design, insertion depth, rough surface
      towards the mucosa, in situ preparation and immediate loading may have an
      influence on the clinical outcome.

PMID- 17501981
TI  - Phenotypic rescue of Chlamydia trachomatis growth in IFN-gamma treated mouse
      cells by irradiated Chlamydia muridarum.
AB  - Chlamydia trachomatis and C. muridarum, human and mouse pathogens, respectively,
      share more than 99% of open reading frames (ORFs) but differ in a cytotoxin
      locus. Presence or absence of cytotoxin gene(s) in these strains correlates with
      their ability to grow in IFN-gamma treated mouse cells. Growth of toxin-positive
      C. muridarum is not affected in IFN-gamma treated cells, whereas growth of toxin
      negative C. trachomatis is inhibited. We previously reported that this difference
      in IFN-gamma sensitivity is important to the in vivo infection tropism of these
      pathogens. Here we describe a phenotypic rescue assay that utilizes C. muridarum
      gamma irradiated killed elementary bodies (iEB) to rescue C. trachomatis
      infectivity in IFN-gamma treated mouse cells. Rescue by iEB was temporal, maximal
      early post infection, directly related to multiplicity of iEB infection, and was
      independent of de novo chlamydial transcription. Lastly, C. muridarum iEB
      vacuoles and C. trachomatis inclusions were not fusogenic, suggesting the
      factor(s) responsible for rescue was secreted or exposed to the cytosol where it
      inactivated IFN-gamma induced effectors. Chlamydial phenotypic rescue may have
      broader utility for the study of other EB associated virulence factors that
      function early in the interaction of chlamydiae with host cells.

PMID- 17501982
TI  - Rac interacts with Abi-1 and WAVE2 to promote an Arp2/3-dependent actin
      recruitment during chlamydial invasion.
AB  - Chlamydiae are Gram-negative obligate intracellular pathogens to which access to
      an intracellular environment is fundamental to their development. Chlamydial
      attachment to host cells induces the activation of the Rac GTPase, which is
      required for the localization of WAVE2 at the sites of chlamydial entry. Co
      immunoprecipitation experiments demonstrated that Chlamydia trachomatis infection
      promoted the interaction of Rac with WAVE2 and Abi-1, but not with IRSp53. siRNA
      depletion of WAVE2 and Abi-1 abrogated chlamydia-induced actin recruitment and
      significantly reduced the uptake of the pathogen by the depleted cells. Chlamydia
      invasion also requires the Arp2/3 complex as demonstrated by its localization to
      the sites of chlamydial attachment and the reduced efficiency of chlamydial
      invasion in cells overexpressing the VCA domain of the neural Wiskott-Aldrich
      syndrome protein. Thus, C. trachomatis activates Rac and promotes its interaction
      with WAVE2 and Abi-1 to activate the Arp2/3 complex resulting in the induction of
      actin cytoskeletal rearrangements that are required for invasion.

PMID- 17501983
TI  - Crystal structure of the BcZBP, a zinc-binding protein from Bacillus cereus.
AB  - Bacillus cereus is an opportunistic pathogenic bacterium closely related to
      Bacillus anthracis, the causative agent of anthrax in mammals. A significant
      portion of the B. cereus chromosomal genes are common to B. anthracis, including
      genes which in B. anthracis code for putative virulence and surface proteins. B.
      cereus thus provides a convenient model organism for studying proteins
      potentially associated with the pathogenicity of the highly infectious B.
      anthracis. The zinc-binding protein of B. cereus, BcZBP, is encoded from the
      bc1534 gene which has three homologues to B. anthracis. The protein exhibits
      deacetylase activity with the N-acetyl moiety of the N-acetylglucosamine and the
      diacetylchitobiose and triacetylchitotriose. However, neither the specific
      substrate of the BcZBP nor the biochemical pathway have been conclusively
      identified. Here, we present the crystal structure of BcZBP at 1.8 A resolution.
      The N-terminal part of the 234 amino acid protein adopts a Rossmann fold whereas
      the C-terminal part consists of two beta-strands and two alpha-helices. In the
      crystal, the protein forms a compact hexamer, in agreement with solution data. A
      zinc binding site and a potential active site have been identified in each
      monomer. These sites have extensive similarities to those found in two known zinc
      dependent hydrolases with deacetylase activity, MshB and LpxC, despite a low
      degree of amino acid sequence identity. The functional implications and a
      possible catalytic mechanism are discussed.

PMID- 17501984
TI  - GrlJ, a Dictyostelium GABAB-like receptor with roles in post-aggregation
      development.
AB  - BACKGROUND: The G-protein-coupled receptor (GPCR) family represents the largest
      and most important group of targets for chemotherapeutics. They are extremely
      versatile receptors that transduce signals as diverse as biogenic amines, purins,
      odorants, ions and pheromones from the extracellular compartment to the interior
      via biochemical processes involving GTP-binding proteins. Until recently, the
      cyclic AMP receptors (cARs) were the only known G protein coupled receptors in
      Dictyostelium discoideum. The completed genome sequence revealed the presence of
      several families of GPCRs in Dictyostelium, among them members of the family 3 of
      GPCRs, the GABAB/glutamate like receptor family, which in higher eukaryotes is
      involved in neuronal signaling. RESULTS: D. discoideum has seventeen Family 3
      members of GPCRs, denoted GrlA through GrlR. Their transcripts are detected
      throughout development with increased levels during early and late development.
      We have examined here GrlJ. GFP-tagged GrlJ localises to the plasma-membrane and
      to internal membranes. Inactivation of the grlJ gene leads to precocious
      development, and the mutant completes development ~6 hours earlier. Alterations
      were also noted at the slug stage and in spore formation. grlJ- slugs were longer
      and broke apart several times on their way to culmination forming smaller but
      proportionate fruiting bodies. Spores from grlJ- fruiting bodies were malformed
      and less viable, although the spore differentiation factors were synthesized and
      sensed normally. Expression of a GFP-tagged full length GrlJ rescued the
      phenotype. CONCLUSION: Our data suggest that GrlJ acts at several stages of
      Dictyostelium development and that it is a negative regulator in Dictyostelium
      development.

PMID- 17501985
TI  - Combination of psychotherapy and benzodiazepines versus either therapy alone for
      panic disorder: a systematic review.
AB  - BACKGROUND: The efficacy of combined psychotherapy and benzodiazepine treatment
      for panic disorder is still unclear despite its widespread use. The present
      systematic review aims to examine its efficacy compared with either monotherapy
      alone. METHODS: All randomised trials comparing combined psychotherapy and
      benzodiazepine for panic disorder with either therapy alone were identified by
      comprehensive electronic search on the Cochrane Registers, by checking references
      of relevant studies and of other reviews, and by contacting experts in the field.
      Two reviewers independently checked eligibility of trials, assessed quality of
      trials and extracted data from eligible trials using a standardized data
      extraction form. Our primary outcome was "response" defined by global judgement.
      Authors of the original trials were contacted for further unpublished data. Meta
      analyses were undertaken synthesizing data from all relevant trials. RESULTS:
      Only two studies, which compared the combination with behaviour (exposure)
      therapy, met our eligibility criteria. Both studies had a 16-week intervention.
      Unpublished data were retrieved for one study. The relative risk for response for
      the combination was 1.25 (95%CI: 0.78 to 2.03) during acute phase treatment, 0.78
      (0.45 to 1.35) at the end of treatment, and 0.62 (0.36 to 1.07) at 6-12 months
      follow-up. Some secondary outcomes hinted at superiority of the combination
      during acute phase treatment. One study was identified comparing the combination
      to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98), 3.39
      (1.03 to 11.21, statistically significant) and 2.31 (0.79 to 6.74) respectively.
      The superiority of the combination was observed on secondary outcomes at all the
      time points. No sub-group analyses were conducted due to the limited number of
      included trials. CONCLUSION: Unlike some narrative reviews in the literature, our
      systematic search established the paucity of high quality evidence for or against
      the combined psychotherapy plus benzodiazepine therapy for panic disorder. Based
      on limited available published and unpublished data, however, the combined
      therapy is probably to be recommended over benzodiazepine alone for panic
      disorder with agoraphobia. The combination might be superior to behaviour therapy
      alone during the acute phase, but afterwards this trend may be reversed. We know
      little from these trials about their adverse effects.

PMID- 17501986
TI  - Atrial and placental melanoma metastasis: a case report and literature review.
AB  - Malignant melanoma can metastasize to virtually any organ of the body. The
      aggressiveness is determined by the primary site, depth of dermal invasion,
      presence or absence of ulceration, lymphovascular infiltration and regional lymph
      node involvement. We report a case of a pregnant woman with a previous history of
      stage 3 melanoma who presented with cardiac metastasis and placental melanoma
      infiltration. A review of literature on cardiac and placental involvement of
      melanoma is also provided.

PMID- 17501988
TI  - Paediatric out-of-hospital resuscitation in an area with scattered population
      (Galicia-Spain).
AB  - BACKGROUND: Cardiorespiratory arrest (CRA) is a rare event in childhood. Our
      objective was to determine the characteristics of paediatric CRA and the
      immediate results of cardiopulmonary resuscitation (CPR) in Galicia, a community
      with a very scattered population. METHODS: All children (aged from newborn to 16
      years old) who suffered an out-of-hospital CRA in Galicia and were assisted by
      the Public Foundation Medical Emergencies of Galicia-061 staff, from June 2002 to
      February 2005, were included in the study. Data were prospectively recorded
      following the Utstein's style guidelines. RESULTS: Thirty-one cases were analyzed
      (3.4 CRA annual cases per 100,000 paediatric population). The arrest was
      respiratory in 16.1% and cardiac in 83.9% of cases. CRA occurred at home in 58.1%
      of instances. Time CRA to initiation of CPR was shorter than 10 minutes in 32.2%
      and longer than 20 minutes in 29.0% of cases. 22.6% of children received
      bystander CPR. The first recorded rhythm was asystole in 67.7% of cases. Bag-mask
      ventilation was used in 67.7% and in 83.8% oro-tracheal intubation was done. A
      peripheral venous access was achieved in 67.7% and intraosseous access was used
      in 16.1% of patients. 93.5% of children were treated with adrenaline. After
      initial CPR, sustained restoration of spontaneous circulation was achieved in
      38.7% of cases. Six children (19.4%) survived until hospital discharge. Four of 5
      children with respiratory arrest survived, whereas only 2 of 26 children with
      cardiac arrest survived until hospital discharge. CONCLUSION: Despite the
      handicap of a highly disseminated population, paediatric CRA characteristics and
      CPR results in Galicia are comparable to references from other communities.
      Programs to increase bystander CPR, equip laypeople with basic CPR skills and to
      update life support knowledge of health staff are needed to improve outcomes.

PMID- 17501989
TI  - The direct cost of "Thriasio" school screening program.
AB  - BACKGROUND: There is great diversity in the policies for scoliosis screening
      worldwide. The initial enthusiasm was succeeded by skepticism and the worth of
      screening programs has been challenged. The criticisms of school screening
      programs cite mainly the negative psychological impact on children and their
      families and the increased financial cost of visits and follow-up radiographs.
      The purpose of this report is to evaluate the direct cost of performing the
      school screening in a district hospital. METHODS: A cost analysis was performed
      for the estimation of the direct cost of the "Thriasio" school-screening program
      between January 2000 and May 2006. The analysis involved all the 6470 pupils aged
      6-18 years old who were screened at schools for spinal deformities during this
      period. The factors which were taken into consideration in order to calculate the
      direct cost of the screening program were a) the number of the examiners b) the
      working hours, c) the examiners' salary, d) the cost of transportation and
      finally e) the cost of examination per child. RESULTS: During the examined period
      20 examiners were involved in the program and worked for 1949 working hours. The
      hourly salary for the trainee doctors was 6.80 euro, for the Health Visitors 6.70
      euro and for the Physiotherapists 5.50 euro in current prices. The cost of
      transportation was 32 euro per year. The direct cost for the examination of each
      child for the above studied period was calculated to be 2.04 euro. CONCLUSION:
      The cost of our school-screening program is low. The present study provides a
      strong evidence for the continuation of the program when looking from a financial
      point of view.

PMID- 17501987
TI  - An overview of tissue engineering approaches for management of spinal cord
      injuries.
AB  - Severe spinal cord injury (SCI) leads to devastating neurological deficits and
      disabilities, which necessitates spending a great deal of health budget for
      psychological and healthcare problems of these patients and their relatives. This
      justifies the cost of research into the new modalities for treatment of spinal
      cord injuries, even in developing countries. Apart from surgical management and
      nerve grafting, several other approaches have been adopted for management of this
      condition including pharmacologic and gene therapy, cell therapy, and use of
      different cell-free or cell-seeded bioscaffolds. In current paper, the recent
      developments for therapeutic delivery of stem and non-stem cells to the site of
      injury, and application of cell-free and cell-seeded natural and synthetic
      scaffolds have been reviewed.

PMID- 17501990
TI  - Species-wide distribution of highly polymorphic minisatellite markers suggests
      past and present genetic exchanges among house mouse subspecies.
AB  - BACKGROUND: Four hypervariable minisatellite loci were scored on a panel of 116
      individuals of various geographical origins representing a large part of the
      diversity present in house mouse subspecies. Internal structures of alleles were
      determined by minisatellite variant repeat mapping PCR to produce maps of
      intermingled patterns of variant repeats along the repeat array. To reconstruct
      the genealogy of these arrays of variable length, the specifically designed
      software MS_Align was used to estimate molecular divergences, graphically
      represented as neighbor-joining trees. RESULTS: Given the high haplotypic
      diversity detected (mean He = 0.962), these minisatellite trees proved to be
      highly informative for tracing past and present genetic exchanges. Examples of
      identical or nearly identical alleles were found across subspecies and in
      geographically very distant locations, together with poor lineage sorting among
      subspecies except for the X-chromosome locus MMS30 in Mus mus musculus. Given the
      high mutation rate of mouse minisatellite loci, this picture cannot be
      interpreted only with simple splitting events followed by retention of
      polymorphism, but implies recurrent gene flow between already differentiated
      entities. CONCLUSION: This strongly suggests that, at least for the chromosomal
      regions under scrutiny, wild house mouse subspecies constitute a set of
      interrelated gene pools still connected through long range gene flow or genetic
      exchanges occurring in the various contact zones existing nowadays or that have
      existed in the past. Identifying genomic regions that do not follow this pattern
      will be a challenging task for pinpointing genes important for speciation.

PMID- 17501991
TI  - Reply to Destaillats, interesterified fats to replace trans fat.
AB  - Although more sophisticated ways exist to analyze TG-MS than that applied in our
      study, the approach was able to identify the TG species sufficiently to emphasize
      the importance of TG structure. The criticism that differences in dietary fat
      saturation alone would explain the lipoprotein response across diets is not
      supported by careful scrutiny of the facts. Nor does fat saturation per se
      address the observed impact that fat structure had on insulin/glucose metabolism.

PMID- 17501992
TI  - Identification of bacteria on the surface of clinically infected and non-infected
      prosthetic hip joints removed during revision arthroplasties by 16S rRNA gene
      sequencing and by microbiological culture.
AB  - It has been postulated that bacteria attached to the surface of prosthetic hip
      joints can cause localised inflammation, resulting in failure of the replacement
      joint. However, diagnosis of infection is difficult with traditional
      microbiological culture methods, and evidence exists that highly fastidious or
      non-cultivable organisms have a role in implant infections. The purpose of this
      study was to use culture and culture-independent methods to detect the bacteria
      present on the surface of prosthetic hip joints removed during revision
      arthroplasties. Ten consecutive revisions were performed by two surgeons, which
      were all clinically and radiologically loose. Five of the hip replacement
      revision surgeries were performed because of clinical infections and five because
      of aseptic loosening. Preoperative and perioperative specimens were obtained from
      each patient and subjected to routine microbiological culture. The prostheses
      removed from each patient were subjected to mild ultrasonication to dislodge
      adherent bacteria, followed by aerobic and anaerobic microbiological culture.
      Bacterial DNA was extracted from each sonicate and the 16S rRNA gene was
      amplified with the universal primer pair 27f/1387r. All 10 specimens were
      positive for the presence of bacteria by both culture and PCR. PCR products were
      then cloned, organised into groups by RFLP analysis and one clone from each group
      was sequenced. Bacteria were identified by comparison of the 16S rRNA gene
      sequences obtained with those deposited in public access sequence databases. A
      total of 512 clones were analysed by RFLP analysis, of which 118 were sequenced.
      Culture methods identified species from the genera Leifsonia (54.3%),
      Staphylococcus (21.7%), Proteus (8.7%), Brevundimonas (6.5%), Salibacillus
      (4.3%), Methylobacterium (2.2%) and Zimmermannella (2.2%). Molecular detection
      methods identified a more diverse microflora. The predominant genus detected was
      Lysobacter, representing 312 (60.9%) of 512 clones analysed. In all, 28
      phylotypes were identified: Lysobacter enzymogenes was the most abundant
      phylotype (31.4%), followed by Lysobacter sp. C3 (28.3%), gamma proteobacterium
      N4-7 (6.6%), Methylobacterium SM4 (4.7%) and Staphylococcus epidermidis (4.7%);
      36 clones (7.0%) represented uncultivable phylotypes. We conclude that a diverse
      range of bacterial species are found within biofilms on the surface of clinically
      infected and non-infected prosthetic hip joints removed during revision
      arthroplasties.

PMID- 17501993
TI  - Incorporation of a lambda phage recombination system and EGFP detection to
      simplify mutagenesis of Herpes simplex virus bacterial artificial chromosomes.
AB  - BACKGROUND: Targeted mutagenesis of the herpesvirus genomes has been facilitated
      by the use of bacterial artificial chromosome (BAC) technology. Such modified
      genomes have potential uses in understanding viral pathogenesis, gene
      identification and characterization, and the development of new viral vectors and
      vaccines. We have previously described the construction of a herpes simplex virus
      2 (HSV-2) BAC and the use of an allele replacement strategy to construct HSV-2
      recombinants. While the BAC mutagenesis procedure is a powerful method to
      generate HSV-2 recombinants, particularly in the absence of selective marker in
      eukaryotic culture, the mutagenesis procedure is still difficult and cumbersome.
      RESULTS: Here we describe the incorporation of a phage lambda recombination
      system into an allele replacement vector. This strategy enables any DNA fragment
      containing the phage attL recombination sites to be efficiently inserted into the
      attR sites of the allele replacement vector using phage lambda clonase. We also
      describe how the incorporation of EGFP into the allele replacement vector can
      facilitate the selection of the desired cross-over recombinant BACs when the
      allele replacement reaction is a viral gene deletion. Finally, we incorporate the
      lambda phage recombination sites directly into an HSV-2 BAC vector for direct
      recombination of gene cassettes using the phage lambda clonase-driven
      recombination reaction. CONCLUSION: Together, these improvements to the
      techniques of HSV BAC mutagenesis will facilitate the construction of recombinant
      herpes simplex viruses and viral vectors.

PMID- 17501994
TI  - Tilescope: online analysis pipeline for high-density tiling microarray data.
AB  - We developed Tilescope, a fully integrated data processing pipeline for analyzing
      high-density tiling-array data http://tilescope.gersteinlab.org. In a completely
      automated fashion, Tilescope will normalize signals between channels and across
      arrays, combine replicate experiments, score each array element, and identify
      genomic features. The program is designed with a modular, three-tiered
      architecture, facilitating parallelism, and a graphic user-friendly interface,
      presenting results in an organized web page, downloadable for further analysis.

PMID- 17501995
TI  - Correlation of umbilical cord blood hormones and growth factors with stem cell
      potential: implications for the prenatal origin of breast cancer hypothesis.
AB  - INTRODUCTION: Prenatal levels of mitogens may influence the lifetime breast
      cancer risk by driving stem cell proliferation and increasing the number of
      target cells, and thereby increasing the chance of mutation events that initiate
      oncogenesis. We examined in umbilical cord blood the correlation of potential
      breast epithelial mitogens, including hormones and growth factors, with
      hematopoietic stem cell concentrations serving as surrogates of overall stem cell
      potential. METHODS: We analyzed cord blood samples from 289 deliveries. Levels of
      hormones and growth factors were correlated with concentrations of stem cell and
      progenitor populations (CD34+ cells, CD34+CD38- cells, CD34+c-kit+ cells, and
      granulocyte-macrophage colony-forming units). Changes in stem cell concentration
      associated with each standard deviation change in mitogens and the associated 95%
      confidence intervals were calculated from multiple regression analysis. RESULTS:
      Cord blood plasma levels of insulin-like growth factor-1 (IGF-1) were strongly
      correlated with all the hematopoietic stem and progenitor concentrations examined
      (one standard-deviation increase in IGF-1 being associated with a 15-19% increase
      in stem/progenitor concentrations, all P < 0.02). Estriol and insulin-like growth
      factor binding protein-3 levels were positively and significantly correlated with
      some of these cell populations. Sex hormone-binding globulin levels were
      negatively correlated with these stem/progenitor pools. These relationships were
      stronger in Caucasians and Hispanics and were weaker or not present in Asian
      Americans and African-Americans. CONCLUSION: Our data support the concept that in
      utero mitogens may drive the expansion of stem cell populations. The correlations
      with IGF-1 and estrogen are noteworthy, as both are crucial for mammary gland
      development.

PMID- 17501996
TI  - The gene expression data of Mycobacterium tuberculosis based on Affymetrix gene
      chips provide insight into regulatory and hypothetical genes.
AB  - BACKGROUND: Tuberculosis remains a leading infectious disease with global public
      health threat. Its control and management have been complicated by multi-drug
      resistance and latent infection, which prompts scientists to find new and more
      effective drugs. With the completion of the genome sequence of the etiologic
      bacterium, Mycobacterium tuberculosis, it is now feasible to search for new drug
      targets by sieving through a large number of gene products and conduct genome
      scale experiments based on microarray technology. However, the full potential of
      genome-wide microarray analysis in configuring interrelationships among all genes
      in M. tuberculosis has yet to be realized. To date, it is only possible to assign
      a function to 52% of proteins predicted in the genome. RESULTS: We conducted a
      functional-genomics study using the high-resolution Affymetrix oligonucleotide
      GeneChip. Approximately one-half of the genes were found to be always expressed,
      including more than 100 predicted conserved hypotheticals, in the genome of M.
      tuberculosis during the log phase of in vitro growth. The gene expression
      profiles were analyzed and visualized through cluster analysis to epitomize the
      full details of genomic behavior. Broad patterns derived from genome-wide
      expression experiments in this study have provided insight into the
      interrelationships among genes in the basic cellular processes of M.
      tuberculosis. CONCLUSION: Our results have confirmed several known gene clusters
      in energy production, information pathways, and lipid metabolism, and also hinted
      at potential roles of hypothetical and regulatory proteins.

PMID- 17501997
TI  - Is zero underestimation feasible? Extended Vacuum-Assisted Breast Biopsy in solid
      lesions - a blind study.
AB  - BACKGROUND: Vacuum-Assisted Breast Biopsy (VABB) is effective for the
      preoperative diagnosis of non-palpable mammographic solid lesions. The main
      disadvantage is underestimation, which might render the management of atypical
      ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) difficult. This
      study aims to develop and assess a modified way of performing VABB. PATIENTS AND
      METHODS: A total of 107 women with non-palpable mammographic breast solid tumors
      BI-RADS 3 and 4 underwent VABB with 11G, on the stereotactic Fischer's table. 54
      women were allocated to the recommended protocol and 24 cores were obtained
      according to the consensus meeting in Nordesterdt (1 offset-main target in the
      middle of the lesion and one offset inside). 53 women were randomly allocated to
      the extended protocol and 96 cores were excised (one offset-main target in the
      middle of the lesion and 7 peripheral offsets). A preoperative diagnosis was
      established. Women with a preoperative diagnosis of
      precursor/preinvasive/invasive lesion underwent open surgery. A second
      pathologist, blind to the preoperative results and to the protocol made the
      postoperative diagnosis. The percentage of the surface excised via VABB was
      retrospectively calculated on the mammogram. The discrepancy between preoperative
      and postoperative diagnoses along with the protocol adopted and the volume
      removed were evaluated by Fisher's exact test and Mann-Whitney-Wilcoxon test,
      respectively. RESULTS: Irrespectively of the protocol adopted, 82.2% of the
      lesions were benign. 14.0% of the lesions were malignancies (5.1% of BI-RADS 3,
      5.3% of BI-RADS 4A, 25% of BI-RADS 4B, and 83.3% of BI-RADS 4C lesions). 3.7% of
      the biopsies were precursor lesions. There was no evidence of underestimation in
      either protocols. In the standard protocol, the preoperative/postoperative
      diagnoses were identical. In the extended protocol, the postoperative diagnosis
      was less severe than the preoperative in 55.5% of cases (55.5% vs. 0%, p =
      0.029), and preoperative ADH was totally removed. The phenomenon of discrepancy
      between diagnoses was associated with larger volume removed (8.20 +/- 1.10 vs.
      3.32 +/- 3.50 cm3, p = 0.037) and higher removed percentage of the lesion (97.83
      +/- 4.86% vs. 74.34 +/- 23.43%, p = 0.024) CONCLUSION: The extended protocol
      seems to totally excise precursor lesions, with minimal underestimation. This
      might possibly point to a modified management of ADH lesions.

PMID- 17501998
TI  - Corneal topographic changes in premenopausal and postmenopausal women.
AB  - BACKGROUND: To asses the effect of menopause on the corneal curvature changes
      using corneal computerized videokeratography (CVK) in premenopausal and
      postmenopausal healthy women. METHODS: Thirty-six postmenopausal women with mean
      ages of 49.2 (range 39 to 57) were enrolled in this randomized, prospective
      study, comparing with 26 healthy controls with mean ages of 38.5 +/- 4.9 (range
      32 to 49). Subjects were determined to be postmenopausal, by the Gynecology and
      Obstetrics Department, based on blood Follicular Stimulating Hormone (FSH),
      Luteinizing Hormone (LH), Estradiol, Progesterone levels and clinical complaints.
      Complete ophthalmic examination and CVK using Haag-Streit System was performed in
      both premenopausal and postmenopausal women. RESULTS: Mean horizontal curvature
      and vertical curvature of central corneal power in premenopausal women were 43.5
      +/- 1.25 Diopter (D), and 44.1 +/- 1.53 D. Mean horizontal curvature and vertical
      curvature of central corneal power in postmenopausal women were 43.9 +/- 1.4 D,
      and 44.6 +/- 1.3 D. The mean keratometric astigmatisms of premenopausal and
      postmenopausal women were 0.81 +/- 0.57 D (4-179 degrees), 0.74 degrees +/- 0.5 D
      (1-180 degrees) respectively. No significant corneal curvature changes were
      detected between premenopausal and postmenopausal groups (P > 0.05). On the other
      hand, we only found negative but significant correlation between horizontal
      corneal curvature and estrogen level of postmenopausal women (r = -0.346, p =
      0.038). CONCLUSION: Menopause is physiologic process and may also affect corneal
      topographic changes. In postmenopausal women, corneal steeping was observed
      minimally compared to premenopausal women. The results suggest that changes in
      estrogen level of women with menopause are associated with slightly alteration of
      horizontal curvature of cornea.

PMID- 17501999
TI  - The economics of primary prevention of cardiovascular disease - a systematic
      review of economic evaluations.
AB  - BACKGROUND: In the quest for public and private resources, prevention continues
      to face a difficult challenge in obtaining tangible public and political support.
      This may be partly because the economic evidence in favour of prevention is often
      said to be largely missing. The overall aim of this paper is to examine whether
      economic evidence in favour of prevention does exist, and if so, what its main
      characteristics, weaknesses and strengths are. We concentrate on the evidence
      regarding primary prevention that targets cardiovascular disease event or risk
      reduction. METHODS: We conducted a systematic literature review of journal
      articles published during the period 1995-2005, based on a comprehensive key-word
      based search in generic and specialized electronic databases, accompanied by
      manual searches of expert databases. The search strategy consisted of
      combinations of freetext and keywords related to economic evaluation,
      cardiovascular diseases, and primary preventive interventions of risk assessment
      or modification. RESULTS: A total of 195 studies fulfilled all of the relevant
      inclusion criteria. Overall, a significant amount of relevant economic evidence
      in favour of prevention does exist, despite important remaining gaps. The
      majority of studies were cost-effectiveness-analyses, expressing benefits as
      "life years gained", were conducted in a US or UK setting, assessed clinical
      prevention, mainly drugs targeted at lowering lipid levels, and referred to
      subjects aged 35-64 years old with at least one risk factor. CONCLUSION: First,
      this review has demonstrated the obvious lack of economic evaluations of broader
      health promotion interventions, when compared to clinical prevention. Second, the
      clear role for government to engage more actively in the economic evaluation of
      prevention has become very obvious, namely, to fill the gap left by private
      industry in terms of the evaluation of broader public health interventions and
      regarding clinical prevention, in light of the documented relationship between
      study funding and reporting of favourable results. Third, the value of greater
      adherence to established guidelines on economic evaluation cannot be emphasised
      enough. Finally, there appear to be certain methodological features in the
      practice of economic evaluations that might bias the choice between prevention
      and cure in favour of the latter.

PMID- 17502000
TI  - Using GIS-based methods of multicriteria analysis to construct socio-economic
      deprivation indices.
AB  - BACKGROUND: Over the past several decades researchers have produced substantial
      evidence of a social gradient in a variety of health outcomes, rising from
      systematic differences in income, education, employment conditions, and family
      dynamics within the population. Social gradients in health are measured using
      deprivation indices, which are typically constructed from aggregated socio
      economic data taken from the national census--a technique which dates back at
      least until the early 1970's. The primary method of index construction over the
      last decade has been a Principal Component Analysis. Seldom are the indices
      constructed from survey-based data sources due to the inherent difficulty in
      validating the subjectivity of the response scores. We argue that this very
      subjectivity can uncover spatial distributions of local health outcomes.
      Moreover, indication of neighbourhood socio-economic status may go
      underrepresented when weighted without expert opinion. In this paper we propose
      the use of geographic information science (GIS) for constructing the index. We
      employ a GIS-based Order Weighted Average (OWA) Multicriteria Analysis (MCA) as a
      technique to validate deprivation indices that are constructed using more
      qualitative data sources. Both OWA and traditional MCA are well known and used
      methodologies in spatial analysis but have had little application in social
      epidemiology. RESULTS: A survey of British Columbia's Medical Health Officers
      (MHOs) was used to populate the MCA-based index. Seven variables were selected
      and weighted based on the survey results. OWA variable weights assign both local
      and global weights to the index variables using a sliding scale, producing a
      range of variable scenarios. The local weights also provide leverage for
      controlling the level of uncertainty in the MHO response scores. This is distinct
      from traditional deprivation indices in that the weighting is simultaneously
      dictated by the original respondent scores and the value of the variables in the
      dataset. CONCLUSION: OWA-based MCA is a sensitive instrument that permits
      incorporation of expert opinion in quantifying socio-economic gradients in health
      status. OWA applies both subjective and objective weights to the index variables,
      thus providing a more rational means of incorporating survey results into spatial
      analysis.

PMID- 17502001
TI  - Predictors of disease progression in HIV infection: a review.
AB  - During the extended clinically latent period associated with Human
      Immunodeficiency Virus (HIV) infection the virus itself is far from latent. This
      phase of infection generally comes to an end with the development of symptomatic
      illness. Understanding the factors affecting disease progression can aid
      treatment commencement and therapeutic monitoring decisions. An example of this
      is the clear utility of CD4+ T-cell count and HIV-RNA for disease stage and
      progression assessment. Elements of the immune response such as the diversity of
      HIV-specific cytotoxic lymphocyte responses and cell-surface CD38 expression
      correlate significantly with the control of viral replication. However, the
      relationship between soluble markers of immune activation and disease progression
      remains inconclusive. In patients on treatment, sustained virological rebound to
      >10,000 copies/mL is associated with poor clinical outcome. However, the same is
      not true of transient elevations of HIV RNA (blips). Another virological factor,
      drug resistance, is becoming a growing problem around the globe and monitoring
      must play a part in the surveillance and control of the epidemic worldwide. The
      links between chemokine receptor tropism and rate of disease progression remain
      uncertain and the clinical utility of monitoring viral strain is yet to be
      determined. The large number of confounding factors has made investigation of the
      roles of race and viral subtype difficult, and further research is needed to
      elucidate their significance. Host factors such as age, HLA and CYP polymorphisms
      and psychosocial factors remain important, though often unalterable, predictors
      of disease progression. Although gender and mode of transmission have a lesser
      role in disease progression, they may impact other markers such as viral load.
      Finally, readily measurable markers of disease such as total lymphocyte count,
      haemoglobin, body mass index and delayed type hypersensitivity may come into
      favour as ART becomes increasingly available in resource-limited parts of the
      world. The influence of these, and other factors, on the clinical progression of
      HIV infection are reviewed in detail, both preceding and following treatment
      initiation.

PMID- 17502002
TI  - Generation of novel high quality HMW-GS genes in two introgression lines of
      Triticum aestivum/Agropyron elongatum.
AB  - BACKGROUND: High molecular weight glutenin subunits (HMW-GS) have been proved to
      be mostly correlated with the processing quality of common wheat (Triticum
      aestivum). But wheat cultivars have limited number of high quality HMW-GS.
      However, novel HMW-GS were found to be present in many wheat asymmetric somatic
      hybrid introgression lines of common wheat/Agropyron elongatum. RESULTS: To
      exploit how these new subunits were generated, we isolated HMW-GS genes from two
      sib hybrid lines (II-12 and 11-4-6) and compared them with those from their
      parents. The result shows that two genes of hybrid (H11-3-3 and H11-4-3) are
      directly introgressed from the donor parent Agropyron elongatum; one hybrid gene
      (H1Dx5) comes from point mutation of a parental wheat gene (1Dx2.1); two other
      hybrid genes (H1By8 and H1By16) are likely resulting from unequal crossover or
      slippage of a parental wheat gene (1By9.1); and the sixth novel hybrid gene
      (H1Dy12) may come from recombination between two parental genes. CONCLUSION:
      Therefore, we demonstrate that novel HMW-GS genes can be rapidly created through
      asymmetric somatic hybridization in a manner similar with the evolution mechanism
      of these genes supposed before. We also described gene shuffling as a new
      mechanism of novel HMW-GS gene formation in hybrids. The results suggest that
      asymmetric somatic hybridization is an important approach for widening HMW-GS
      genebank of wheat quality improvement.

PMID- 17502005
TI  - The effect of erythropoietin on healing of obstructive vs nonobstructive left
      colonic anastomosis: an experimental study.
AB  - BACKGROUND: Anastomotic leakage is an important problem following primary
      resection in the left colon and is even more prominent when obstruction is
      present. We aimed to evaluate the possible effects of erythropoietin on the
      healing of anastomosis under both obstructive and non-obstructive states.
      METHODS: Forty male Wistar albino rats were divided into four groups. In group I,
      two cm left colonic resection and primary anastomosis were done. In group II,
      left colon were completely ligated and 24 hours later animals were re-operated
      for segmental resection. The same procedures were performed for rats in group III
      and IV in respect to group I and II and, 500 IU/kg a day erythropoietin were
      given in the latter two groups for seven days. For the quantative description of
      anastomotic healing mechanical, biochemical and histopathological parameters were
      employed on the seventh day and the animals were sacrificied. RESULTS: Although
      erythropoietin had positive effects on bursting pressure in group IV when
      compared to group II, it has no effect in group III. Despite the increased tissue
      hydroxyproline levels in group IV, erythropoietin failed to show any effects in
      group III. Erythropoietin had positive effects on neovascularization, fibroblast
      proliferiation and storage of collagen in group IV. CONCLUSION: We failed to find
      any direct and evident effects of erythropoietin on healing of left colonic
      anastomosis. On the other hand, erythropoietin might prevent negative effects of
      obstruction on healing.

PMID- 17502004
TI  - Transcriptional analysis of an immune-responsive serine protease from Indian
      malarial vector, Anopheles culicifacies.
AB  - BACKGROUND: The main vector for transmission of malaria in India is the Anopheles
      culicifacies mosquito species, a naturally selected subgroup of which is
      completely refractory (R) to transmission of the malaria parasite, Plasmodium
      vivax; RESULTS: Here, we report the molecular characterization of a serine
      protease (acsp30)-encoding gene from A. culicifacies, which was expressed in high
      abundance in the refractory strain compared to the susceptible (S) strain. The
      transcriptional upregulation of acsp30 upon Plasmodium challenge in the
      refractory strain coincided with ookinete invasion of mosquito midgut. Gene
      organization and primary sequence of acsp30 were identical in the R and S strains
      suggesting a divergent regulatory status of acsp30 in these strains. To examine
      this further, the upstream regulatory sequences of acsp30 were isolated, cloned
      and evaluated for the presence of promoter activity. The 702 bp upstream region
      of acsp30 from the two strains revealed sequence divergence. The promoter
      activity measured by luciferase-based reporter assay was shown to be 1.5-fold
      higher in the R strain than in the S. Gel shift experiments demonstrated a
      differential recruitment of nuclear proteins to upstream sequences of acsp30 as
      well as a difference in the composition of nuclear proteins in the two strains,
      both of which might contribute to the relative abundance of acsp30 in the R
      strain; CONCLUSION: The specific upregulation of acsp30 in the R strain only in
      response to Plasmodium infection is suggestive of its role in contributing the
      refractory phenotype to the A. culicifacies mosquito population.

PMID- 17502006
TI  - Is there any relation between insulin resistance and cognitive function in the
      elderly?
AB  - BACKGROUND: Vascular risk factors are blamed as being involved in the
      pathogenesis of cognitive dysfunction in the elderly. Alzheimer's disease or
      vascular-type dementia could be part of a metabolic syndrome. The aim of this
      study was to evaluate whether there is any relation between insulin resistance
      and cognitive status of the elderly regarding normal, mild cognitive impairment
      (MCI), Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia.
      METHODS: 267 elderly patients admitted to an outpatient geriatrics clinic were
      evaluated medically and cognitively in this study. The patients were diagnosed
      using ARDRA and DSM-IV criteria for AD; NINDS-AIREN and DSM-IV criteria for VaD;
      and Petersen criteria for MCI. Insulin resistance was calculated using both the
      homeostasis model assessment (HOMA) and quantitative insulin sensitivity check
      index (QUICKI) formulas. RESULTS: The mean values of HOMA and QUICKI scores were
      2.79 (SD+/-3.56) and 0.346 (SD+/-0.036) for the normal group, 2.81 (SD+/-3.06)
      and 0.354 (SD+/-0.047) for AD group, 2.20 (SD+/-1.82) and 0.360 (SD+/-0.048) for
      VaD group, 2.87 (SD+/-1.81) and 0.339 (SD+/-0.038) for mixed dementia group, 2.79
      (SD+/-2.81) and 0,349 (SD+/-0.042) for MCI group, respectively. There were no
      statistically significant differences between HOMA and QUICKI scores of all the
      groups. CONCLUSION: This is the first study of the possible relation between
      insulin resistance and cognitive function in people categorized according to five
      forms of cognitive status. Unfortunately the results do not allow
      generalizations. Further prospective cohort studies that follow a normal
      cognitive group and MCI patients with and without insulin resistance are
      necessary.

PMID- 17502003
TI  - Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating
      and steroid-like activities of ginsenosides.
AB  - In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a
      general tonic or an adaptogen to promote longevity and enhance bodily functions.
      It has also been claimed to be effective in combating stress, fatigue, oxidants,
      cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are
      attributed to one type of its constituents, namely the ginsenosides. In this
      review, we focus on the recent advances in the study of ginsenosides on
      angiogenesis which is related to many pathological conditions including tumor
      progression and cardiovascular dysfunctions. Angiogenesis in the human body is
      regulated by two sets of counteracting factors, angiogenic stimulators and
      inhibitors. The 'Yin and Yang' action of ginseng on angiomodulation was
      paralleled by the experimental data showing angiogenesis was indeed related to
      the compositional ratio between ginsenosides Rg1 and Rb1. Rg1 was later found to
      stimulate angiogenesis through augmenting the production of nitric oxide (NO) and
      vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such
      responses were mediated through the PI3K-->Akt pathway. By means of DNA
      microarray, a group of genes related to cell adhesion, migration and cytoskeleton
      were found to be up-regulated in endothelial cells. These gene products may
      interact in a hierarchical cascade pattern to modulate cell architectural
      dynamics which is concomitant to the observed phenomena in angiogenesis. By
      contrast, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg3
      and Rh2) have been demonstrated in various models of tumor and endothelial cells,
      indicating that ginsenosides with opposing activities are present in ginseng.
      Ginsenosides and Panax ginseng extracts have been shown to exert protective
      effects on vascular dysfunctions, such as hypertension, atherosclerotic disorders
      and ischemic injury. Recent work has demonstrates the target molecules of
      ginsenosides to be a group of nuclear steroid hormone receptors. These lines of
      evidence support that the interaction between ginsenosides and various nuclear
      steroid hormone receptors may explain the diverse pharmacological activities of
      ginseng. These findings may also lead to development of more efficacious ginseng
      derived therapeutics for angiogenesis-related diseases.

PMID- 17502007
TI  - Mini-mental State Examination performance in mild cognitive impairment subtypes.
AB  - BACKGROUND: Diagnosis of mild cognitive impairment (MCI) and its subtypes
      requires a detailed diagnostic assessment and so may be missed at routine primary
      care appointments, since the ordinary dementia screening tests lack sensitivity
      owing to ceiling effects, especially in highly educated subjects. METHODS: The
      study was undertaken using a cross-sectional assessment of 112 elderly subjects
      (mean age 67.96+/-5.77 years, and mean education level of 12.8+/-5.7 years) with
      a semi-structured interview and a neuropsychological battery. RESULTS: MCI
      patients did not differ from controls on total MMSE scores (p=0.212).
      Nevertheless, MCI patients showed worse performance than controls on the verbal
      memory task (p=0.012), and "drawing a pentagon" (p=0.03). Amnestic MCI patients
      performed worse only on the "three-word recall" task (p=0.013); non-amnestic MCI
      patients performed worse on the "three-stage command" task (p=0.001); and
      multiple-domain MCI patients performed worse on the "drawing a pentagon" task
      (p=0.001) and had a trend toward performing poorly on the 'three word recall'
      task (p=0.06). CONCLUSION: The analysis of MMSE subtest scores, in addition to
      MMSE total scores, may increase the sensitivity of the MMSE test in screening for
      MCI and its subtypes.

PMID- 17502008
TI  - Lemierre's syndrome associated with consumption coagulopathy and acute renal
      failure: a case report.
AB  - BACKGROUND: Acute tonsillitis or pharyngitis may lead to suppurative
      thrombophlebitis of the internal jugular vein. This complication, also known as
      Lemierre's syndrome, remains, even nowadays, life threatening, due to
      dissemination of septic thromboemboli to various organs. Respiratory deficiency
      and renal impairment are often reported in patients suffering from Lemierre's
      syndrome. CASE REPORT: The unusual clinical manifestation of this case involves
      severe acute renal and respiratory deficiency in addition to microangiopathic
      consumption coagulopathy in a young patient treated with macrolides five days
      after the onset of acute tonsillitis. CONCLUSION: The usual causative pathogen,
      namely Fusobacterium necrophorum, shows a varying sensitivity to macrolides. As a
      result, the syndrome may present itself in a variety of clinical forms even in
      patients under treatment with macrolides. A high index of suspicion is therefore
      crucial for in time prevention of potentially life threatening complications.

PMID- 17502010
TI  - [Development and question about interventional therapy for cerebrovascular
      disease].

PMID- 17502011
TI  - [Treatment of wide-necked cerebral aneurysms using stent and balloon-assisted
      technique].
AB  - OBJECTIVE: To discuss the avail of balloon and stent-assisted Guglielmi
      detachable coil (GDC) placement in treatment of wide-necked cerebral aneurysm.
      METHODS: Eighty-seven patients with 92 wide-necked aneurysms undergone
      endovascular procedures using the balloon and stent-assisted remodeling
      technique. Respectively, appropriate Neuroform stents delivered with a 5 mm
      landing zone on either side of the aneurysm neck, the microcatheter entered
      through the interstice, aneurysms were embolized at one or several times. Two
      catheters were used in balloon-remodeling technique, balloon were inflated across
      the neck of the aneurysms after the microcatheter entering the aneurysms, then
      the GDC were used to embolize the aneurysms. RESULTS: Thirty-one aneurysms were
      completely occluded, 3 subtotally (> 90%) and 1 incompletely (70% - 90%) occluded
      using stent-assisted technique, all carry arteries were unblocked, 3 patients
      with mild neurological dysfunction and no mortality. Fifty aneurysms were
      completely occluded and 4 incompletely occluded using balloon-assisted technique,
      1 patients with mild neurological dysfunction and no mortality. Two aneurysms
      were completely occluded and 1 incompletely occluded using stent-assisted and
      balloon-assisted technique. The mean period of follow-up was 5.8 months. Rates of
      recanalization were 16.7% for stent-remodeling group and 12.5% for balloon
      remodeling group. CONCLUSIONS: The stent and balloon-assisted remodeling
      technique are safe and effective in treating wide-necked aneurysms. Balloon
      remodeling technique has more security comparing with stents.

PMID- 17502012
TI  - [Clinical experience of 70 cases of cerebral arteriovenous malformations
      embolization with Onyx, a novel liquid embolic agent].
AB  - OBJECTIVE: To report our clinical experience of using Onyx, a new liquid embolic
      agent, to treat cerebral arteriovenous malformations (AVMs) as well as its
      efficacy. METHODS: Seventy cases were placed with 6F sheath in the femoral artery
      after Seldinger puncture and 6F guiding catheter was introduced into the internal
      carotid artery or vertebral artery, then a microcatheter was navigated into the
      nidus of AVMs. Slow injection of Onyx under fluoroscopic control was performed to
      embolize cerebral AVMs using the "plug and push" technique. RESULTS: Thirteen AVM
      cases (18.6%) were totally occluded by Onyx and 5 cases of which didn't
      recurrence at 6-month after operation. Thirty-eight cases (54.3%) were subtotally
      occluded, while another 19 cases (27.1%) were partially embolized. Severe
      cerebral hemorrhage occurred in 4 cases, 2 of which had mild to severe hemiplegia
      after operation, and one died. Mild hemiplegia was also found in 1 case due to
      functional area embolization, and visual field deficit in 2 cases. CONCLUSIONS:
      Onyx has unique and distinctive superiority in treating cerebral AVMs.
      Nonetheless, the correct embolization technique should be learned to achieve good
      clinical results and avoid complications.

PMID- 17502013
TI  - [Management of elderly patients with symptomatic vertebrobasilar insufficiency].
AB  - OBJECTIVE: To evaluate the feasibility, safety and short-term efficacy of stent
      assisted angioplasty and/or drug therapy for elderly patients with symptomatic
      vertebrobasilar insufficiency. METHODS: Elderly patients (> or = 60 years old)
      with symptomatic vertebrobasilar stenosis (> or = 50%) demonstrated by cerebral
      angiography were treated with drug therapy and some with endovascular stenting
      further from April 2001 to June 2006. The clinical, imaging, intervention and
      follow-up data were collected and analyzed. RESULTS: Eighty-one elderly patients
      were chosen for study, including 68 males and 13 females. The mean age is 70
      years (60 - 87 years); stroke rate of 4.9% (4/81) and stroke-related mortality
      rate of 2.5% (2/81) were found in this group during hospitalization and follow-up
      (mean 28.1 months), and symptoms resolved or improved clinically in 66 (81.5%).
      Fifty-two balloon expandable stents were placed in 48 (59.3%) patients of this
      group with a technical success rate of 98.1% and the mean degree of stenosis was
      reduced from (82.4 +/- 13.1)% to (6.4 +/- 3.2)% (t = 22.4, P = 0.00).
      CONCLUSIONS: Appropriate management including endovascular stenting and/or drug
      therapy may improve short-term outcomes of elderly patients with symptomatic
      vertebrobasilar insufficiency; meanwhile, stent-assisted angioplasty is
      technically feasible and relatively safe.

PMID- 17502014
TI  - [Clinical study about the management of hemodynamic instability during carotid
      stenting angioplasty].
AB  - OBJECTIVE: To evaluate the validity of different treatment for minimizing the
      complications caused by hemodynamic changes during stenting angioplasty of
      carotid stenoses. METHODS: There was no special measure for 80 of 205 cases
      during angioplasty. General blood pressure was controlled strictly to normal
      lower limit for avoiding intracranial reperfusion bleeding and angioplasty was
      done after elevated heart rate to 80 per minute in the remaining 125 cases.
      RESULTS: There were 8.8% complications in 80 cases and no obviously complication
      occurred in 125 cases controlling hemodynamic changes. Follow-up period from 1
      months to 5 years, there was no marked restenosis. CONCLUSION: Regulating
      hemodynamic changes should be emphasized for reducing complications and improving
      the effect of carotid artery stenting.

PMID- 17502016
TI  - [The early diagnosis and therapy of aneurismal subarachnoid hemorrhage].
AB  - OBJECTIVE: To discuss the early diagnostic methods and therapeutic principles of
      aneurysmal subarachnoid hemorrhage (SAH), and evaluate the therapeutic efficacy
      objectively. METHODS: Using neuro-imaging examinations combined with case history
      and clinical symptoms to make the early diagnosis of 96 case with aneurysmal SAH,
      and Guglielmi detachable microcoil (GDC) was utilized for early intracapsular
      embolization in the ruptured aneurysms. Efficient symptomatic treatment was done
      early after operation. RESULTS: All of 96 cases were early diagnosed and
      successfully embolized; Among them, the aneurysmal lumen was 100% occluded in 83
      cases, 95% in 8 cases, 90% in 5 cases. There were 3 cases complicating with
      aneurysms rupture during operation, 5 cases with cerebral vasospasm. One case was
      affected by microcoil terminal escape after operation, 3 recurrent cases were all
      cured with secondary GDC embolization. There were 9 complications associated with
      embolization techniques and 13 cases (13.5%) occurring permanent sequelae
      associated with SAH. According to the Glasgow prognosis score, 77 patients got
      grade I, 7 grade II, 6 grade III, 3 grade IV, and 3 grade V. The mortality rate
      was 3.1%. CONCLUSIONS: To make early etiological diagnosis of the SAH patients,
      using GDC to embolize the aneurysms, and earlier efficient symptomatic treatment
      are important methods to improve the curative rate and reduce the mortality rate.

PMID- 17502019
TI  - [Accuracy and related affecting factors of somatosensory evoked potential
      monitoring in cervical and thoracic surgery].
AB  - OBJECTIVE: To evaluate the accuracy and related affecting factors of the intra
      operative somatosensory evoked potential monitoring in cervical and thoracic
      surgery. METHODS: Cortical somatosensory evoked potential (CSEP) monitoring and
      sub cortical somatosensory evoked potential (Sub-CSEP) monitoring were performed
      in cervical and thoracic surgery. Somatosensory evoked potential (SEP) changes
      were recorded during anaesthesia and operation and postoperative, which could be
      used to evaluate accuracy of SEP. RESULTS: Bilateral CSEP wave abnormalities were
      related to anaesthesia, decreasing wave amplitudes did not reach the alarming
      standard. Intra-operative manipulation to affect spinal cord would influence iso
      lateral wave abnormality of CSEP and sub-CSEP, decreasing amplitudes reached the
      alarming standard. Local hypothermia such as cold water irrigating spinal cord
      would be to prolong the latent period. Low mean arterial pressure (MAP) mostly
      influenced amplitudes. Changes of SEP in local hypothermia and MAP did not reach
      the alarming standard. CONCLUSIONS: CSEP and Sub CSEP can reflex
      physiopathological condition of spinal cord, it is useful in evaluating spinal
      cord function and providing the safety for cervical and thoracic surgery.

PMID- 17502020
TI  - [Observation of the sectional anatomic structure and visualization of the normal
      lumbar plexus of virtual Chinese human].
AB  - OBJECTIVE: To observe the normal structure of lumbar plexus in the virtual
      Chinese Human (VCH) Female I and Male III and establish a digitized visible model
      of their lumbar plexus. METHODS: The cross-sectional images from the VCH Female I
      and Male III dataset were reviewed to study lumbar plexus structures on a section
      by-section basis. The nerve roots, major psoas muscle and blood vessels were also
      observed. Three-dimensional computerized reconstructions of lumbar plexus and its
      adjacent structures were conducted from these data using Amira 3.1 (TGS) imaging
      software respectively. RESULTS: The three-dimensional reconstructed visible
      models perfectly displayed the anatomic relationships of lumbar plexus structures
      and their adjacent structures. CONCLUSIONS: VCH Female I and Male III dataset can
      provide complete and accurate data of main structure of lumbar plexus. The
      digitized models of lumbar plexus offer unique insights into the complex anatomy,
      and morphologic data for imaging diagnosis and treatment of the injury of lumbar
      plexus.

PMID- 17502021
TI  - [The second stage revision for infected total hip arthroplasty using antibiotic
      loaded cement prosthesis].
AB  - OBJECTIVE: To investigate the effect of two-stage revision for infected total hip
      arthroplasty (THA) using antibiotic-loaded cement prosthesis. METHODS: From June
      1999 to October 2004, 14 patients who admitted for infected primary total hip
      arthroplasty surgeries were performed revision surgery with antibiotic-loaded
      cement prosthesis in two-stage. The mean Harris score of pre-operation was 23. In
      the first stage operation, the following steps were performed, complete
      debridement, removal of infected prosthesis, implantation of cement spacer with
      antibiotics, treatment involved concomitant administration of 3 weeks of
      intravenous (IV) and 1 month of oral. After 6 months, antibiotic-loaded
      prosthesis was implanted in the second stage. RESULTS: The mean follow-up was 18
      months (7 - 26 months), no recurrent infection occurred in all 14 patients. The
      mean post-operation Harris score was 70. CONCLUSIONS: The success of the protocol
      to control the delayed infection after THA are complete debridement, enough
      interval and using antibiotic-loaded cement prosthesis in two stage revision.

PMID- 17502022
TI  - [Early operative treatment of pelvic fractures associated with urethral
      disruption].
AB  - OBJECTIVE: To evaluate the early operative treatment and clinical results of
      pelvic fractures associated with urethra disruption. METHODS: From January 1995
      to January 2005, 25 patients suffered from pelvic fractures combined urethra
      disruption treated by operation were retrospectively analyzed. According to
      Tile's classification, 1 case was stable pelvic fracture, 17 rotational unstable
      fractures, and 7 rotational combined vertical unstable fractures. The complete
      urethra rupture were in 23 cases and incomplete in 2 cases. The operative methods
      included: (1) emergency open reduction and internal fixation of the pelvis
      combined primary urethra suturing in 2 cases, partial suturing after realignment
      in 4 cases, realignment in 2 cases, and urethrovaginal penetrating wound
      repairing in 1 case; (2) primary urethra realignment only and delayed (range, 7
      to 21 days) pelvic internal fixation in 10 cases; (3) early cystostomy and
      delayed (range, 3 to 21 days) urethra realignment and pelvic internal fixation in
      6 cases. RESULTS: The mean follow-up time of all patients was 34 months (range
      from 6 to 120 months). According to Majeed's evaluation, 17 cases of pelvic
      injury showed excellent results, 5 good, and 3 fare. After urinary catheter
      removed, the mean maximal urine flow rate of 19 (76%) patients was 18.6 ml/s and
      the mean scar length between both disrupted ends on the film of excretion
      urethrography was 0.51 cm. Five (20%) cases suffered in dysuria needed urethral
      dilatation or further surgery. One (4%) female could not control urination who
      need a second-look operation. The primary suprapubic soft tissue avulsion wound
      infection secondary to retropubic abscess was found in 1 case, posterior urethra
      stenosis in 5 cases, sexual impotence in 3 cases, and incontinence in 1 case.
      CONCLUSIONS: The satisfactory reduction and effective fixation of the pelvic
      fractures is an anatomical basis for receiving "tension-free urethral
      anastomosis".

PMID- 17502023
TI  - [The protective effects on allografts of adeno-associated heme-oxygenase-1 gene
      therapy against chronic rejection injury].
AB  - OBJECTIVE: To investigate the protective effects on allografts and the possible
      mechanism of adeno-associated heme-oxygenase-1 (AdHO-1) gene therapy against
      chronic rejection injury. METHODS: Ex vivo AdHO-1 gene therapy was performed in
      vascular and renal transplantation models. The structure and function, the
      expression of therapeutic genes and proteins, and the immune modulation were
      analyzed. RESULTS: AdHO-1 gene therapy protected renal transplant against chronic
      rejection, but the effect was not as remarkable as that in vascular transplant.
      The transfected empty vehicle aggravated chronic rejection damage in renal
      transplantation. AdHO-1 decreased the infiltration of macrophages and CD4(+) T
      cells. CONCLUSIONS: AdHO-1 gene therapy can lessen damage of chronic rejection in
      allografts. It plays roles by protecting transplants, down-regulating immune
      response and inducing immune deviation.

PMID- 17502024
TI  - [Effects of LRIG1 gene on the invasion of bladder cancer in vitro].
AB  - OBJECTIVE: To observe the change of invasion ability of the bladder cancer cell
      line BIU87 after transfected with LRIG1 gene. METHODS: Plasmid pLRIG1-GFP was
      transfected into bladder cancer cells (BIU87) by Lipofectamine 2000, and cells
      that could express LRIG1 stably was screened out by G418. The alteration of
      cellular invasion property of BIU87, BIU87-neo and BIU87-LRIG1 cells was
      evaluated by Boyden chamber. The expression of mRNA and protein of LRIG1 and EGFR
      was detected by RT-PCR and Western-blot. RESULTS: Compared with BIU87 and BIU87
      neo cells, after BIU87 cell line was transfected with plasmid pLRIG1-GFP, the
      invasion ability decreased significantly, the expression of mRNA and protein of
      LRIG1 was obviously up-regulated and that of EGFR was down-regulated (P < 0.01).
      CONCLUSION: LRIG1 gene can significantly inhibit the invasion ability of BIU87
      cell line.

PMID- 17502025
TI  - [Establishment of obliterative bronchiolitis in allo-trachea transplant model of
      rat and detection of its pathogenesis preliminarily].
AB  - OBJECTIVE: To establish an animal model of obliterative bronchiolitis (OB) after
      lung transplantation and investigate the pathogenesis preliminarily. METHODS:
      Tracheal segments (5 cartilaginous rings each) were transplanted from SD rats to
      SD rats (Group I) or to Wistar rats (Group II and III). Grafts were implanted
      into an abdominal cavity and wrapped in the omentum. Animals in Group I and II
      did not receive CsA, animals in Group III received CsA daily by gastro-tube at 10
      mg.kg(-1).d(-1) from beginning to end. Grafts were harvested on day 3, 14, 28
      after transplantation as representative time points for 3 phases of injury in the
      evolution of allograft airway obliteration, then examined histological changes
      and gene expression of T-helper 1-and T-helper 2-type cytokines [Th1: interleukin
      2 (IL-2), interferon-gamma (IFN-gamma); Th2: interleukin-4 (IL-4), interleukin-10
      (IL-10)] in grafts. At the same time, effects of CsA were observed on the above
      mentioned indices. RESULTS: There was no significant difference in histological
      changes on day 3 after transplantation among 3 groups (P > 0.05). Tracheas in
      Group I approached to normal morphology on day 14 after transplantation. Airway
      epithelium of Group II and III almost lost completely on day 14 after
      transplantation. There was no significant difference between Group II and Group
      III (P > 0.05), but there were significant differences between Group I and Group
      II or Group III. The cross-sectional area of the tracheal lumen was narrowed by
      approximately (5.0 +/- 1.2)%, (28.5 +/- 5.0)% and (19.4 +/- 2.9)% respectively on
      day 14 after transplantation in Group I, II and III, there were significant
      differences among 3 groups. On day 14 after transplantation, tracheas in Group I
      revealed few lymphocytic infiltration, but it showed dense lymphocytic
      infiltration in Group II. Tracheas in Group III have much more lymphocyte
      infiltration than that in Group I, but much less than that in Group II. There
      were significant differences among 3 groups, too (P < 0.01). The tracheal lumen
      revealed almost total luminal obstruction (94.8 +/- 3.6)% on day 28 after
      transplantation in Group II. The cross-sectional area of the tracheal lumen was
      narrowed by approximately (3.7 +/- 0.8)% and (36.6 +/- 7.6)% respectively in
      Group I and III on day 28. There were significant differences among 3 groups (P <
      0.01). Compared with that on day 14, lymphocytic infiltration had decreased
      gradually on day 28 in Group II and III. There were significant differences among
      3 groups all the same (P < 0.01). In Group II, expression of IL-2, IFN-gamma, IL
      4, and IL-10 were much higher than that in Group I. Expression of Th1 cytokines
      was increased to a greater extent than that of Th2 cytokines in Group II compared
      with Group I. Allografts in Group III expressed significantly less IL-2 gene
      transcripts than that in Group II over all the points. There was no significant
      difference between Group II and III in IFN-gamma, IL-4, and IL-10 gene
      expression. CONCLUSIONS: Compared with isografts, allografts have more obvious
      changes, such as epithelial damage, fibroproliferation and lymphocytic
      infiltration. Th1 and Th2 lymphocyte subtypes contribute to the development of
      obliterative bronchiolitis in heterotopic trachea transplant model of rat, and
      changes of their cytokines gene expression may be involved in the pathogenesis.
      CsA could reduce the development of fibroproliferation and lymphocyte
      infiltration markedly, but it could not protect airway epithelium. CsA inhibits
      IL-2 gene transcripts, so it can reduce development of the pathologic lesion of
      obliterative bronchiolitis to a certain degree.

PMID- 17502038
TI  - Interleukin 17-producing T-helper cells and autoimmune diseases: time for a
      paradigm shift?

PMID- 17502039
TI  - Epidemiology, etiology, detection, and treatment of autoantibody-associated
      congenital heart block in neonatal lupus.
AB  - Neonatal lupus syndrome is a model of passively acquired autoimmunity in which
      the pregnant woman's serum contains specific antibodies to 52 or 60 kd SSA/Ro
      and/or 48 kd SSB/La, which cross the placenta and are associated with the
      development of congenital heart block in the fetus and/or a transient rash or
      various liver and blood cell abnormalities in the newborn. To date, congenital
      heart block is a permanent condition that entails significant morbidity and
      mortality, with nearly all affected infants requiring pacemakers and with an 80%
      cumulative probability of survival at 3 years of age. An intensive search is on
      for the specific etiopathophysiology and for new clinical tools to approach and
      treat this disease.

PMID- 17502040
TI  - Neurologic manifestations of the antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is an important cause of neurologic morbidity. The
      clinical criteria for antiphospholipid syndrome include only cerebrovascular
      arterial and venous thrombosis, but many other neurologic manifestations have
      been associated with antiphospholipid antibodies (aPL). This review discusses the
      role of aPL in cerebrovascular manifestations and in some of the other neurologic
      manifestations commonly associated with these antibodies, as well as data
      pertaining to the pathophysiology of aPL-associated neurologic manifestations and
      treatment issues.

PMID- 17502041
TI  - New insights into central nervous system lupus: a clinical perspective.
AB  - Patients with systemic lupus erythematosus (SLE) experience a wide array of
      neurologic (N) and psychiatric (P) events, some of which are directly
      attributable to lupus. Regardless of attribution, NP events have a significant
      impact on individual patient's health-related quality of life. Primary
      immunopathogenic mechanisms of NP-SLE include vasculopathy, autoantibody
      production, and intrathecal inflammatory mediators. The recently described anti
      NR2 glutamate receptor antibodies have been implicated in animal models of
      neuronal injury, but their role in the pathogenesis of human NP-SLE is unclear.
      The diagnosis of NP-SLE remains largely one of exclusion, although the detection
      of select autoantibodies, CSF analysis, and appropriate use of neuroimaging and
      neuropsychometric testing may provide support in the evaluation of individual
      patients. Therapeutic options include symptomatic therapies, immunosuppression,
      and anticoagulation.

PMID- 17502042
TI  - The role of preventive cardiology in systemic lupus erythematosus.
AB  - With improved therapeutic advances in the care of systemic lupus erythematosus
      patients, cardiovascular disease has emerged as a leading cause of death.
      Premature atherosclerosis in lupus patients is probably an interaction between
      traditional cardiovascular risk factors, inflammatory factors, and factors
      related to lupus itself. Despite knowledge of this accelerated cardiac risk,
      evaluation of traditional risk factors has been sub-par. We propose that lupus
      patients be evaluated by preventive cardiologists and have access to their
      expertise and resources. In addition to nephrologists and dermatologists,
      preventive cardiologists should be an integral part of the care of patients with
      lupus.

PMID- 17502044
TI  - New developments in fibroblast and myofibroblast biology: implications for
      fibrosis and scleroderma.
AB  - The concept of mesenchymal fibroblasts has evolved over the past two decades from
      a relatively inert structural cell type to a dynamic, pluripotent cell lineage
      controlling normal connective tissue formation, homeostasis, and repair and as
      principle players in pathogenic scarring and fibrosis. In wound healing and
      tissue repair, fibroblasts provide proinflammatory signals and synthesize
      interstitial collagens, fibronectins, and other matrix components to repair the
      damaged tissue. Fibroblasts can differentiate into the myofibroblast, a
      specialized contractile cell type responsible for wound closure, tissue
      contraction, and scarring. This article reviews our current understanding of the
      origins of mesenchymal cells and their role in excessive scarring and
      fibrogenesis and in the systemic fibrotic disease scleroderma.

PMID- 17502045
TI  - Management of interstitial lung disease in systemic sclerosis: lessons from SLS
      and FAST.
AB  - Interstitial lung disease (ILD) is a leading cause of death in systemic sclerosis
      (SSc). Two randomized controlled trials recently demonstrated the modest effects
      of cyclophosphamide on lung physiology (forced vital capacity) and extrapulmonary
      outcomes (dyspnea, function, quality of life, and skin thickening).
      Recommendations can now be made about the short-term management for SSc-ILD.
      However, many questions remain unanswered, including how long to treat with
      cyclophosphamide; whether patients should take maintenance therapy after the
      initial or induction phase; whether there are alternative therapies; how to treat
      patients with ILD and pulmonary hypertension; and how to treat patients with
      severe ILD.

PMID- 17502047
TI  - Therapy of pulmonary arterial hypertension in systemic sclerosis: an update.
AB  - Pulmonary arterial hypertension (PAH) affects 10% to 15% of patients with
      systemic sclerosis and is a major cause for disease-related morbidity and
      mortality. Over the past decade, significant progress has been made in the
      understanding of the pathophysiologic mechanisms underlying PAH. This progress
      led to the development of several new treatment options and, as a result,
      dramatically improved survival among this severely affected cohort. The outcome
      in patients with scleroderma-related PAH is much worse than that in patients with
      idiopathic PAH, and unfortunately only a few studies have assessed treatment and
      outcome among patients suffering from connective tissue disease-related PAH. In
      recent years, publications of connective tissue disease subgroup analysis from
      large trials in PAH have emerged. We review the current treatment options for PAH
      and the evidence for their use in scleroderma-related PAH.

PMID- 17502046
TI  - Outcome measures in systemic sclerosis: an update on instruments and current
      research.
AB  - Substantial progress has been made in the past 10 years in the development and
      validation of outcome measures and refinement of trial methodology for systemic
      sclerosis (scleroderma, SSc). These advances in outcome measures have focused
      mostly on specific organ systems involved in SSc. Many of these new tools have
      been validated and subsequently adapted for use in multicenter clinical trials.
      Newer outcome measures in development are intended to more precisely quantify
      clinically meaningful change in specific organ systems, and some methods aim to
      assess overall disease burden in SSc. This review provides an update on currently
      used outcome measures in SSc with specific attention on newer tools and also
      describes methodology under development.

PMID- 17502050
TI  - [Biochemical mechanisms in the global impacts of the atmospheric pollution: a
      research continuum].

PMID- 17502048
TI  - Autoimmunity in systemic sclerosis: current concepts.
AB  - Systemic sclerosis (SSc) is characterized by tissue fibrosis, obliterative
      microangiopathy, and immune abnormalities. The role of autoimmunity in generating
      the clinical and pathologic phenotype in SSc remains uncertain. Distinct subsets
      of antinuclear antibodies are selectively associated with unique disease
      manifestations but do not have a proven pathogenic role. A new class of
      autoantibodies recognizing cellular or extracellular matrix antigens has been
      recognized in SSc patients. They seem to directly activate pathways that may
      contribute to SSc-specific tissue and vascular damage. Data confirms that
      activation and polarization of T cells can contribute to a profibrotic
      environment. Also, activated immune effector cells can promote vascular
      obliterative damage through direct cytotoxic pathways targeting the endothelium
      or by inducing proinflammatory molecules. Technologies are emerging to accurately
      measure the autoantigen-specific T-cell response in SSc patients. Perturbed B
      cell homeostasis has been reported in SSc. If confirmed in-vivo, these advances
      could lead to new disease-modifying therapeutic strategies directed at SSc
      specific immune effector pathways.

PMID- 17502049
TI  - Current concepts in normal and defective angiogenesis: implications for systemic
      sclerosis.
AB  - Vascular abnormalities are a major component of systemic sclerosis, but little is
      known about the events or mechanisms that initiate vascular injury and prevent
      its repair. Early stages of systemic sclerosis are characterized by an
      exaggerated angiogenic response later replaced by defective wound healing and
      fibrosis. In this review, we summarize the current knowledge of the angiogenic
      imbalance in systemic sclerosis.

PMID- 17502051
TI  - [PTEN: a guard of nuclear safety].

PMID- 17502052
TI  - [Evolutionary history of Salmonella Typhi illustrates a new pattern of
      epidemiologic dynamics].

PMID- 17502053
TI  - [Alpha/beta versus gamma/delta T cell development: a choice linked to the
      transcription factor Sox13].

PMID- 17502054
TI  - [EDIN of S. aureus induces the formation of large transcellular tunnels in
      endothelial cells and increases vascular permeability].

PMID- 17502055
TI  - [Hepatitis C virus and lipid droplets].

PMID- 17502056
TI  - [Pathogens trapped in neutrophils nets].

PMID- 17502057
TI  - [FoxO: stress or eternal life].

PMID- 17502058
TI  - [On the evolution of the chordates bodyplan].

PMID- 17502059
TI  - [Immunoglobulin gene hypermutation: when error becomes a quality].

PMID- 17502060
TI  - [Secretory cytotoxic granule maturation is required to their lytic contents
      excretion].

PMID- 17502061
TI  - [ICSI and calcium signaling].

PMID- 17502062
TI  - [Counting proteins in a single cell].

PMID- 17502063
TI  - [Origin of liver murine oval cells].

PMID- 17502064
TI  - [Idiopathic hypogonadotropic hypogonadism according to Mendel].

PMID- 17502065
TI  - [Air pollution and respiratory diseases: a central role for oxidative stress].
AB  - Epidemiological studies have clearly shown a relationship between respiratory
      diseases and air pollution. Ozone and ambient particles are the main pollutants
      contributing to the exacerbation of these pathologies. Their toxicity resides in
      their ability to generate an oxidative stress. The level of oxidative stress and
      the specificity of the cellular responses result from complex interactions
      between pro- and anti-oxidants, leading to differentiated cellular strategies.
      Hierarchical biological responses: adaptation, inflammation, lesions, can be
      determined according to the oxidative insult and individual anti-oxidant
      capacities. A better health risk assessment could be achieved by taking into
      account the oxidative properties of air pollution especially those of ultrafine
      particles.

PMID- 17502066
TI  - [Potential role of NK cells in future anti-tumor immunotherapies].
AB  - Natural Killer (NK) cells are no longer considered as relatively unimportant
      bystander cells having the capacity to kill certain tumor and virus-infected
      cells in a mysterious way. During the last decade a significant progress has been
      made in understanding biology of NK cells in particular their mechanisms of
      recognition and killing of target cells. This progress has led to novel knowledge
      based clinical applications of NK cells as immunotherapeutic tools in various
      disease settings, especially in bone marrow transplantation for leukemia
      patients. The potential of NK cell therapy for eradicating solid tumors has not
      been fully exploited. In this mini-review, we examine the rationale behind these
      therapies and discuss the problems confronting researchers in their usage as
      therapeutic agents.

PMID- 17502067
TI  - [MicroRNAs and intestinal pathophysiology].
AB  - MicroRNAs (miRNAs) represent an abundant class of endogenously expressed small
      RNAs, which is believed to control the expression of proteins through specific
      interaction with their mRNAs. MiRNAs are non-coding RNAs of 18 to 24 nucleotides
      that negatively regulate target mRNAs by binding to their 3'-untranslated regions
      (UTR). Most eukaryotic cells utilize miRNA to regulate vital functions such as
      cell differentiation, proliferation or apopotosis. The diversity of miRNAs and of
      their mRNA targets strongly indicate that they play a key role in the regulation
      of protein expression. To date, more than 500 different miRNAs have been
      identified in animals and plants. There are at least 326 miRNAs in the human
      genome, comprising 1-4% of all expressed human genes, which makes miRNAs one of
      the largest classes of gene regulators. A single miRNA can bind to and regulate
      many different mRNA targets and, conversely, several different miRNAs can bind to
      and cooperatively control a single mRNA target. The correlation between the
      expression of miRNAs and their effects on tumorigenesis and on the proliferation
      of cancer cells is beginning to gain experimental evidences. Recent studies
      showed that abnormal expression of miRNAs represents a common feature of cancer
      cells and that they can function as tumor suppressor genes or as oncogenes.
      Therefore, this diversity of action for miRNAs on several target genes could be
      one of the common mechanisms involved in the deregulation of protein expression
      observed during intestinal disorders. In this review, the emergent functions of
      miRNAs in colorectal cancer and their potential role in the intestinal
      inflammatory process are discussed.

PMID- 17502068
TI  - [PPARs and cell-cell or cell-extracellular matrix interactions].
AB  - The peroxisome proliferator-activated receptors (PPARs) are transcription factors
      and belong to the superfamily of nuclear receptors. They are encoded by three
      genes located on different chromosomes: PPARalpha, PPARbeta/delta and PPARgamma.
      PPARalpha plays a key role in the control of lipid metabolism and homeostasis.
      PPARbeta/delta is expressed ubiquitously and participates in skeletal muscle
      physiology. PPARbeta/delta and PPARgamma are important factors for placental
      development and function as well as for embryo implantation. In addition,
      PPARgamma is mainly involved in adipogenesis. PPARs also participate more or less
      to cell proliferation, differentiation and apoptosis. Surprisingly, the
      involvement of these transcription factors in cell-cell and/or cell-matrix
      interactions has not yet been reviewed except for their role as therapeutic
      agents in inflammation. Nevertheless, several pioneer reports have recently
      provided some new insights in this research field, by suggesting that PPARs are
      involved, directly or indirectly, in these interactions and that their activation
      by specific ligands may lead to potential therapeutic approaches.

PMID- 17502069
TI  - [Targeting allotopic material to the mitochondrial compartment: new tools for
      better understanding mitochondrial physiology and prospect for therapy].
AB  - Mitochondrial disorders can not be ignored anymore in most medical areas. They
      include specific and widespread organ involvement, with tissue degeneration or
      tumor formation, being the target of numerous viruses, e.g. the HIV. Primary or
      secondary actors, mitochondrial dysfunctions are also supposedly playing a role
      in the ageing process. Despite the progresses made in the identification of their
      molecular bases, nearly all remains to be done as regards therapy. Research
      dealing with mitochondrial physiology and pathology has a long history in France
      and is thus not a surprise if four French teams, coming from these fundamental
      domains, are involved in the challenge to find ways to fight these diseases. The
      directions described are working tracks which promise to be long and full of
      pitfalls. Being original, they share a part of risk and uncertainty, but they are
      also with great potential with high stakes if considering the impact of these
      diseases.

PMID- 17502070
TI  - [The X+ chronic granulomatous disease as a fabulous model to study the NADPH
      oxidase complex activation].
AB  - Chronic granulomatous disease (CGD) is a rare inherited disorder in which
      phagocytes lack NADPH oxidase activity. Patients with CGD suffer from recurrent
      bacterial and fungal infections because of the absence of superoxide anions (O2-
      degrees ) generatingsystem. The NADPH oxidase complex is composed of a membranous
      cytochrome b558, cytosolic proteins p67phox, p47phox, p40phox and two small
      GTPases Rac2 and Rap1A. Cytochrome b558 consists of two sub-units gp91phox and
      p22phox. The most common form of CGD is due to mutations in CYBB gene encoding
      gp91phox. In some rare cases, the mutated gp91phox is normally expressed but is
      devoided of oxidase activity. These variants called X+ CGD, have provided
      interesting informations about oxidase activation mechanisms. However
      modelization of such variants is necessary to obtain enough biological material
      for studies at the molecular level. A cellular model (knock-out PLB-985 cells)
      has been developed for expressing recombinant mutated gp91phox for functional
      analysis of the oxidase complex. Recent works demonstrated that this cell line
      genetically deficient in gp91phox is a powerful tool for functional analysis of
      the NADPH oxidase complex activation.

PMID- 17502071
TI  - [Medical demography: how to fight against the medical deserts?].

PMID- 17502072
TI  - [The general practitioners in front of reforms: the reactions of the sample group
      of liberal physicians of the region PACA].
AB  - The general practitioners in front of reforms: the reactions of the sample group
      of liberal physicians of the region PACA This article intends to analyse the
      opinion of general practioners (GPs) about the two laws of July 2004, relating to
      the health insurance reform and to public health planning. We used a panel data
      sample of 528 GPs practising in Provence Alpes Cote d'Azur in order to analyse
      the determinants of physicians' adherence to the reform, using multinomial
      logistic regression models. The results show that GPs do not seem to be fully
      convinced by this reform (45% agree with it, whereas 48% don't): this mistrustful
      opinion is more marked for young physicians and appears little correlated with
      their practices. 75% of the GPs are favourable to the Personal Medical File
      (Dossier Medical Personnel in french) and 76% estimate that they should draw a
      better attention to the public health dimension of their practice. Two barriers
      concerning GPs' adherence to the << preferred doctor >> reform (reforme du <<
      medecin traitant >>) seem relevant: the burden of administrative tasks and the
      disadvantage of young physicians who have not already fixed their own clientele.

PMID- 17502073
TI  - [Genetics and business: in defence of free speech!].

PMID- 17502074
TI  - [About the neonatal screening of cystic fibrosis].

PMID- 17502075
TI  - [Is the enigma of Napoleon's death finally resolved?].

PMID- 17502076
TI  - [Can a large epidemic for the new variant of Creutzfeldt-Jakob disease be
      feared?].

PMID- 17502077
TI  - [A competition of synthetic biology or how to create the "water of E. coli" and
      nano-barbies].

PMID- 17502078
TI  - [Genetics programming, behavior and cognition in psychiatry (Dominique Campion)].

PMID- 17502079
TI  - [When two molecules involved in the regulation of mood meet: mutual modulation of
      the serotonin transporter and neuronal NO-synthase].

PMID- 17502080
TI  - [IGF1, an allele for the small dogs].

PMID- 17502081
TI  - Cuckoos.

PMID- 17502082
TI  - On speaking, writing and inspiration.

PMID- 17502083
TI  - Microbial biofilms: e pluribus unum.

PMID- 17502084
TI  - Interactions between circadian rhythm and immunity in Drosophila melanogaster.

PMID- 17502085
TI  - Female-led infanticide in wild chimpanzees.

PMID- 17502086
TI  - Cell spreading: the power to simplify.
AB  - A eukaryotic cell spreads over a substrate in distinct stages, with the earliest
      events characterized by passive adhesion and cell deformation. Recent work
      suggests a common physical mechanism can explain the early stages of cell
      spreading for a wide range of cell types and substrates.

PMID- 17502087
TI  - Brain stimulation: feeling the buzz.
AB  - A recent study demonstrates that artificially generated patterns of brain
      activity are surprisingly easy to sense. Brain areas that differ substantially in
      their functional specialization are remarkably similar in their ability to
      support this awareness.

PMID- 17502088
TI  - Dispersal ecology: where have all the seeds gone?
AB  - How effective are different animals at dispersing seeds? A new study has traced
      seeds sampled in faeces to their mother of origin and concluded that carnivorous
      mammals can be better dispersers than birds.

PMID- 17502089
TI  - Olfactory processing: massive convergence onto sparse codes.
AB  - Sparse neural coding provides numerous computational advantages. A recent
      analysis of the locust olfactory system has revealed a surprising circuit
      solution for achieving remarkably sparse and specific neural representations of
      odors.

PMID- 17502090
TI  - Chimpanzee violence: femmes fatales.
AB  - New observations of coalitionary infanticide by female chimpanzees in Uganda shed
      light on the nature of female competition.

PMID- 17502091
TI  - Memory formation: sleep enough before learning.
AB  - Is a full night of sleep a waste of time? No, numerous studies show dramatic
      performance impairments after sleep restriction, and a new study now indicates
      that sleep deprivation diminishes the brain's ability to form new memories.

PMID- 17502092
TI  - Evolutionary biology: variation isn't always sexy.
AB  - A recent study has found that differences in a male trait, considered a textbook
      example of sexual selection, are in fact due to naturally selected variation in
      the aerodynamic optimum for each individual.

PMID- 17502093
TI  - Face cells: separate processing of expression and gaze in the amygdala.
AB  - A neuroimaging study in monkeys has shown that separate regions of the amygdala
      are responsive to facial expression and gaze/head orientation.

PMID- 17502094
TI  - A systematics for discovering the fundamental units of bacterial diversity.
AB  - Bacterial systematists face unique challenges when trying to identify
      ecologically meaningful units of biological diversity. Whereas plant and animal
      systematists are guided by a theory-based concept of species, microbiologists
      have yet to agree upon a set of ecological and evolutionary properties that will
      serve to define a bacterial species. Advances in molecular techniques have given
      us a glimpse of the tremendous diversity present within the microbial world, but
      significant work remains to be done in order to understand the ecological and
      evolutionary dynamics that can account for the origin, maintenance, and
      distribution of that diversity. We have developed a conceptual framework that
      uses ecological and evolutionary theory to identify the DNA sequence clusters
      most likely corresponding to the fundamental units of bacterial diversity. Taking
      into account diverse models of bacterial evolution, we argue that bacterial
      systematics should seek to identify ecologically distinct groups with evidence of
      a history of coexistence, as based on interpretation of sequence clusters. This
      would establish a theory-based species unit that holds the dynamic properties
      broadly attributed to species outside of microbiology.

PMID- 17502095
TI  - Myosin mechanochemistry.

PMID- 17502096
TI  - Caspase inhibition, specifically.

PMID- 17502097
TI  - A computational tool for designing FRET protein biosensors by rigid-body sampling
      of their conformational space.
AB  - Biosensors relying on the fluorescence resonance energy transfer (FRET) between
      fluorescent proteins have been used for live-cell imaging of cellular events
      including Ca(2+) signaling. The efficiency of energy transfer between the donor
      and acceptor fluorescent proteins depends on the relative distance and
      orientation between them, which become altered by conformational changes of a
      fused sensory protein caused by a cellular event. In this way, changes in FRET
      efficiency of Ca(2+) biosensors can be correlated with Ca(2+) concentrations. The
      design of these FRET biosensors can be improved by modeling conformational
      changes before and after a cellular event. Hence, a computational tool called
      FPMOD was developed to predict FRET efficiency changes by constructing FRET
      biosensors and sampling their conformational space through rigid-body rotation.
      We showed with FPMOD that our computational modeling approach can qualitatively
      predict the FRET efficiencies of a range of biosensors, which had strong
      agreement with experimental results.

PMID- 17502098
TI  - Crystal structures of the BAR-PH and PTB domains of human APPL1.
AB  - APPL1 interacts with adiponectin receptors and other important signaling
      molecules. It contains a BAR and a PH domain near its N terminus, and the two
      domains may function as a unit (BAR-PH domain). We report here the crystal
      structures of the BAR-PH and PTB domains of human APPL1. The structures reveal
      novel features for BAR domain dimerization and for the interactions between the
      BAR and PH domains. The BAR domain dimer of APPL1 contains two four-helical
      bundles, whereas other BAR domain dimers have only three helices in each bundle.
      The PH domain is located at the opposite ends of the BAR domain dimer. Yeast two
      hybrid assays confirm the interactions between the BAR and PH domains. Lipid
      binding assays show that the BAR, PH, and PTB domains can bind phospholipids. The
      ability of APPL1 to interact with multiple signaling molecules and phospholipids
      supports an important role for this adaptor in cell signaling.

PMID- 17502099
TI  - The structure of chagasin in complex with a cysteine protease clarifies the
      binding mode and evolution of an inhibitor family.
AB  - Protein inhibitors of proteolytic enzymes regulate proteolysis and prevent the
      pathological effects of excess endogenous or exogenous proteases. Cysteine
      proteases are a large family of enzymes found throughout the plant and animal
      kingdoms. Disturbance of the equilibrium between cysteine proteases and natural
      inhibitors is a key event in the pathogenesis of cancer, rheumatoid arthritis,
      osteoporosis, and emphysema. A family (I42) of cysteine protease inhibitors
      (http://merops.sanger.ac.uk) was discovered in protozoan parasites and recently
      found widely distributed in prokaryotes and eukaryotes. We report the 2.2 A
      crystal structure of the signature member of the I42 family, chagasin, in complex
      with a cysteine protease. Chagasin has a unique variant of the immunoglobulin
      fold with homology to human CD8alpha. Interactions of chagasin with a target
      protease are reminiscent of the cystatin family inhibitors. Protein inhibitors of
      cysteine proteases may have evolved more than once on nonhomologous scaffolds.

PMID- 17502100
TI  - The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol.
AB  - Proprotein convertase subtilisin kexin type 9 (PCSK9) has been shown to be
      involved in the regulation of extracellular levels of the low-density lipoprotien
      receptor (LDLR). Although PCSK9 is a subtilase, it has not been shown to degrade
      the LDLR, and its LDLR-lowering mechanism remains uncertain. Here we report the
      crystal structure of human PCSK9 at 2.3 A resolution. PCSK9 has subtilisin-like
      pro- and catalytic domains, and the stable interaction between these domains
      prevents access to PCSK9's catalytic site. The C-terminal domain of PCSK9 has a
      novel protein fold and may mediate protein-protein interactions. The structure of
      PCSK9 provides insight into its biochemical characteristics and biological
      function.

PMID- 17502101
TI  - Rigor-like structures from muscle myosins reveal key mechanical elements in the
      transduction pathways of this allosteric motor.
AB  - Unlike processive cellular motors such as myosin V, whose structure has recently
      been determined in a "rigor-like" conformation, myosin II from contracting muscle
      filaments necessarily spends most of its time detached from actin. By using squid
      and sea scallop sources, however, we have now obtained similar rigor-like atomic
      structures for muscle myosin heads (S1). The significance of the hallmark closed
      actin-binding cleft in these crystal structures is supported here by actin/S1
      binding studies. These structures reveal how different duty ratios, and hence
      cellular functions, of the myosin isoforms may be accounted for, in part, on the
      basis of detailed differences in interdomain contacts. Moreover, the rigor-like
      position of switch II turns out to be unique for myosin V. The overall
      arrangements of subdomains in the motor are relatively conserved in each of the
      known contractile states, and we explore qualitatively the energetics of these
      states.

PMID- 17502102
TI  - Thorough validation of protein normal mode analysis: a comparative study with
      essential dynamics.
AB  - The deformation patterns of a large set of representative proteins determined by
      essential dynamics extracted from atomistic simulations and coarse-grained normal
      mode analysis are compared. Our analysis shows that the deformational space
      obtained with both approaches is quite similar when taking into account a
      representative number of modes. The results provide not only a comprehensive
      validation of the use of a low-frequency modal spectrum to describe protein
      flexibility, but also a complete picture of normal mode limitations.

PMID- 17502103
TI  - Structural basis for dynamic interdomain movement and RNA recognition of the
      selenocysteine-specific elongation factor SelB.
AB  - Selenocysteine (Sec) is the "21st" amino acid and is genetically encoded by an
      unusual incorporation system. The stop codon UGA becomes a Sec codon when the
      selenocysteine insertion sequence (SECIS) exists downstream of UGA. Sec
      incorporation requires a specific elongation factor, SelB, which recognizes
      tRNA(Sec) via use of an EF-Tu-like domain and the SECIS mRNA hairpin via use of a
      C-terminal domain (SelB-C). SelB functions in multiple translational steps:
      binding to SECIS mRNA and tRNA(Sec), delivery of tRNA(Sec) onto an A site, GTP
      hydrolysis, and release from tRNA and mRNA. However, this dynamic mechanism
      remains to be revealed. Here, we report a large domain rearrangement in the
      structure of SelB-C complexed with RNA. Surprisingly, the interdomain region
      forms new interactions with the phosphate backbone of a neighboring RNA, distinct
      from SECIS RNA binding. This SelB-RNA interaction is sequence independent,
      possibly reflecting SelB-tRNA/-rRNA recognitions. Based on these data, the
      dynamic SelB-ribosome-mRNA-tRNA interactions will be discussed.

PMID- 17502104
TI  - Structure of the calcineurin-NFAT complex: defining a T cell activation switch
      using solution NMR and crystal coordinates.
AB  - Calcineurin (Cn) is a serine/threonine protein phosphatase that plays pivotal
      roles in many physiological processes, including cell proliferation, development,
      and apoptosis. Most prominently, Cn targets the nuclear factors of activated T
      cell (NFATs), transcription factors that activate cytokine genes. Calcium
      activated Cn dephosphorylates multiple residues within the regulatory domain of
      NFAT, triggering joint nuclear translocation. This relies crucially on the
      interaction between the catalytic domain of Cn (CnCat) and the conserved PxIxIT
      motif located in a region distinct from the dephosphorylation sites of NFAT.
      Here, we present the structure of the complex between the 39 kDa CnCat and a 14
      residue peptide containing a PVIVIT segment that was derived from affinity-driven
      peptide selection based on the conserved PxIxIT motif of NFATs. The structure of
      the complex was determined by using NMR assignments and structural constraints
      and the coordinates of the CnCat crystal structure. The NMR analysis relied on
      recently developed labeling and spectroscopic techniques. The VIVIT peptide is
      accommodated in a hydrophobic cleft formed by beta strands 11 and 14, and the
      loop between beta strands 11 and 12, forming a short parallel beta sheet with the
      exposed beta strand 14 in Cn. The side chains of conserved residues in the PxIxIT
      sequences make extensive interactions with conserved residues in Cn, while those
      of nonconserved residues are solvent exposed. The architecture of the interface
      explains the diversity of recognition sequences compatible with NFAT function and
      uncovers a potential targeting site for immune-suppressive agents. The structure
      reveals that the orientation of the bound PxIxIT directs the phosphorylation
      sites in NFAT's regulatory domain toward the Cn catalytic site.

PMID- 17502105
TI  - Fluorescent human RAD51 reveals multiple nucleation sites and filament segments
      tightly associated along a single DNA molecule.
AB  - The DNA strand-exchange reactions defining homologous recombination involve
      transient, nonuniform allosteric interactions between recombinase proteins and
      their DNA substrates. To study these mechanistic aspects of homologous
      recombination, we produced functional fluorescent human RAD51 recombinase and
      visualized recombinase interactions with single DNA molecules in both static and
      dynamic conditions. We observe that RAD51 nucleates filament formation at
      multiple sites on double-stranded DNA. This avid nucleation results in multiple
      RAD51 filament segments along a DNA molecule. Analysis of fluorescent filament
      patch size and filament kinks from scanning force microscopy (SFM) images
      indicate nucleation occurs minimally once every 500 bp. Filament segments did not
      rearrange along DNA, indicating tight association of the ATP-bound protein. The
      kinetics of filament disassembly was defined by activating ATP hydrolysis and
      following individual filaments in real time.

PMID- 17502106
TI  - The signaling pathway of rhodopsin.
AB  - The signal-transduction mechanism of rhodopsin was studied by molecular dynamics
      (MD) simulations of the high-resolution, inactive structure in an explicit
      membrane environment. The simulations were employed to calculate equal-time
      correlations of the fluctuating interaction energy of residue pairs. The
      resulting interaction-correlation matrix was used to determine a network that
      couples retinal to the cytoplasmic interface, where transducin binds. Two highly
      conserved motifs, D(E)RY and NPxxY, were found to have strong interaction
      correlation with retinal. MD simulations with restraints on each transmembrane
      helix indicated that the major signal-transduction pathway involves the
      interdigitating side chains of helices VI and VII. The functional roles of
      specific residues were elucidated by the calculated effect of retinal
      isomerization from 11-cis to all-trans on the residue-residue interaction
      pattern. It is suggested that Glu134 may act as a "signal amplifier" and that
      Asp83 may introduce a threshold to prevent background noise from activating
      rhodopsin.

PMID- 17502107
TI  - Inhibition of caspase-2 by a designed ankyrin repeat protein: specificity,
      structure, and inhibition mechanism.
AB  - Specific and potent caspase inhibitors are indispensable for the dissection of
      the intricate pathways leading to apoptosis. We selected a designed ankyrin
      repeat protein (DARPin) from a combinatorial library that inhibits caspase-2 in
      vitro with a subnanomolar inhibition constant and, in contrast to the peptidic
      caspase inhibitors, with very high specificity for this particular caspase. The
      crystal structure of this inhibitor (AR_F8) in complex with caspase-2 reveals the
      molecular basis for the specificity and, together with kinetic analyses, the
      allosteric mechanism of inhibition. The structure also shows a conformation of
      the active site that can be exploited for the design of inhibitory compounds.
      AR_F8 is a specific inhibitor of an initiator caspase and has the potential to
      help identify the function of caspase-2 in the complex biological apoptotic
      signaling network.

PMID- 17502108
TI  - A new evidence for DNA nicking property of amyloid beta-peptide (1-42): relevance
      to Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex neurodegenerative disorder with a
      progressive mental deterioration manifested by memory loss. No definite etiology
      has been established for AD to date. Amyloid beta (Abeta) protein plays a central
      role in the pathology of AD through multiple pathways like oxidative stress,
      apoptosis etc. Recently, our laboratory first time has evidenced localization of
      Abeta immunoreactivity in apoptotic nuclei of degenerating AD brain hippocampal
      neurons and also showed that Abeta (1-42) binds and alters the helicity of DNA.
      The present study provided fundamental data on DNA nicking induced by Abeta. The
      results showed that Abeta (1-42) has DNA nicking activity similar to nucleases.
      Further, magnesium ion (1mM) enhanced DNA nicking activity of Abeta. The data on
      Abeta solution stability on DNA nicking revealed that the oligomers of Abeta (1
      42) peptides showed more DNA nicking activity compared to monomers and fibrillar
      forms. The nuclease specific inhibitor aurintricarboxylic acid prevented the DNA
      nicking property of Abeta. Transmission electron microscopy (TEM) studies
      revealed that Abeta causes open circular and linear forms in supercoiled DNA and
      also clearly evidenced the physical association of protein-DNA complex. The above
      data indicated that Abeta mimics endonuclease behavior. Our finding of DNA
      nicking activity of Abeta peptides has biological significance in terms of
      causing direct DNA damage.

PMID- 17502109
TI  - Sulfur dioxide derivatives modulate Na/Ca exchange currents and cytosolic [Ca2+]i
      in rat myocytes.
AB  - We have recently shown that sulfur dioxide (SO(2)) derivatives (bisulfite and
      sulfite, 1:3 M/M) modulated L-type calcium, sodium, and potassium channels in rat
      myocytes. The aim of this study was to investigate whether SO(2) derivatives
      could alter Na/Ca exchanger current and the intracellular free [Ca(2+)]. The
      nickel-sensitive Na/Ca exchanger current was measured in rat myocytes exposed to
      ramp pulses in Tyrode's solution containing ouabain, nifedipine, and +/-Ni (5
      mmol/l). Myocytes were loaded with the fluorescent Ca(2+) indicator Fura-2/AM to
      estimate intracellular Ca(2+) concentration. SO(2) derivatives significantly
      inhibited both outward and inward Ni-sensitive Na/Ca exchanger currents without a
      shift in the reversal potential. The intracellular free [Ca(2+)] was raised by
      SO(2) derivatives in several concentrations. SO(2) derivatives increased
      [Ca(2+)](i) in rat myocytes and its mechanism might involve SO(2) derivatives
      significantly inhibiting Na/Ca exchanger current and enhancing L-type calcium
      channel.

PMID- 17502110
TI  - HnRNP A3 binds to and protects mammalian telomeric repeats in vitro.
AB  - The biological function of hnRNP family proteins is widely diverse and involved
      in pre-mRNA processing, transcriptional regulation, recombination, and telomere
      maintenance. In the course of our study on the elucidation of biological
      functions of minisatellite DNA, we isolated several nuclear proteins that bind to
      the mouse minisatellite Pc-1, which consists of a tandem array of d(GGCAG)
      repeats, from NIH3T3 cells. One of the minisatellite binding proteins, MNBP-A,
      which binds to a single-stranded G-rich strand of the Pc-1 repeat, was proven
      identical to the hnRNP A3. Recombinant hnRNP A3 was demonstrated to bind to the
      single-stranded telomeric d(TTAGGG) repeat with much higher affinity than the
      d(GGCAG) repeat. Binding of hnRNP A3 to the single-stranded telomeric repeat
      protected the repeat from nuclease attack, and inhibited both telomerase reaction
      and DNA synthesis in vitro. These results suggest a possible biological role of
      hnRNP A3 in the stable maintenance of telomere repeats.

PMID- 17502111
TI  - Inhibitory effect of recombinant adenovirus carrying immunocaspase-3 on
      hepatocellular carcinoma.
AB  - Previously, Srinivasula devised a contiguous molecule (C-cp-3 or immunocaspase-3)
      containing the small and large subunits similar to that in the active form of
      caspas-3 and found C-cp-3 had similar cleavage activity to the active form of
      caspase-3. To search for a new clinical application of C-cp-3 to treat
      hepatocellular carcinoma, recombinant adenoviruses carrying the C-cp-3 and a
      fetoprotein (AFP) promoter (Ad-rAFP-C-cp-3) were constructed through a bacterial
      homologous recombinant system. The efficiency of adenovirus-mediated gene
      transfer and the inhibitory effect of Ad-rAFP-C-cp-3 on the proliferation of
      hepatocarcinoma cells were determined by X-gal stain and MTT assay, respectively.
      The tumorigenicity of hepatocarcinoma cells transfected by Ad-rAFP-C-cp-3 and the
      antitumor effect of Ad-rAFP-C-cp-3 on transplanted tumor in nude mice were
      detected in vivo. The results suggested that Ad-rAFP-C-cp-3 can inhibit
      specifically proliferation of AFP-producing human hepatocarcinoma cells in vitro
      and in vivo and adenovirus-mediated C-cp-3 transfer could be used as a new method
      to treat human hepatocarcinoma.

PMID- 17502112
TI  - Expression and physiological regulation of BDNF receptors in the neuroendocrine
      melanotrope cell of Xenopus laevis.
AB  - Brain-derived neurotrophic factor (BDNF) and alpha-melanophore-stimulating
      hormone (alpha-MSH) are co-sequestered in secretory granules in melanotrope cells
      of the pituitary pars intermedia of the amphibian Xenopus laevis. alpha-MSH is
      responsible for pigment dispersion in dermal melanophores during the process of
      black-background adaptation. BDNF-production in melanotrope cells is increased by
      placing animals on a black background, and BDNF acts as an autocrine stimulatory
      factor on the melanotrope cells. However, the repertoire of possible neurotrophin
      receptors of the melanotrope is unknown. In this study we have established the
      expression of full length TrkB (TrkB.FL), truncated TrkB (TrkB.T) and p75(NTR)
      receptors in the Xenopus neurointermediate lobe by RT-PCR. In situ hybridization
      reveals the presence of TrkB.FL mRNA and p75(NTR) mRNA in melanotrope cells.
      Quantitative RT-PCR shows that in animals on a black background the amounts of
      TrkB.T and p75(NTR) mRNA are about three times higher than in white background
      adapted animals. We suggest that the amount of p75(NTR) sets the sensitivity of
      the melanotrope cells for the stimulatory action of BDNF during physiological
      adaptation to background light intensity.

PMID- 17502113
TI  - Collinearity improves alignment in amblyopia as well as in normal vision.
AB  - In normal vision, three contrast patches containing black and white bars are
      aligned more precisely when the bars are collinear across the patches [Popple,
      A., Polat, U., & Bonneh, Y. (2001). Collinear effects on 3-Gabor alignment as a
      function of spacing, orientation and detectability. Spatial Vision, 14(2), 139
      150]. Normally, offsets between the bars in successive patches make the
      configuration appear tilted, but this effect is reduced in amblyopia [Popple, A.
      V., & Levi, D. M. (2000). Amblyopes see true alignment where normal observers see
      illusory tilt. Proceedings of the National Academy of Science of the United
      States of America, 97(21), 11667-11672]. Our aim was to examine whether collinear
      bars nonetheless improve the precision of alignment in amblyopia. In a sample of
      13 amblyopes, we found that collinear bars did indeed improve the precision of
      alignment in amblyopia, although both alignment bias and thresholds were higher
      in the amblyopic eyes for both collinear and non-collinear bars.

PMID- 17502115
TI  - Spatial and temporal crowding in amblyopia.
AB  - Spatial crowding is a well-known deficit in amblyopia. We have previously
      reported evidence suggesting that the inability to isolate stimuli in space in
      crowded displays (spatial crowding) is a largely independent component of the
      amblyopic deficit in visual acuity, which is typically found in strabismic
      amblyopia [Bonneh, Y., Sagi, D., & Polat, U. (2004a). Local and non-local
      deficits in amblyopia: Acuity and spatial interactions. Vision Research, 44, 3009
      3110]. Here, we extend this result to the temporal domain by measuring visual
      acuity (VA) for a single pattern in a rapid serial visual presentation (RSVP-VA,
      N=15) for fast ("crowded") and slow ("uncrowded") presentations. We found that
      strabismic amblyopes but not anisometropic amblyopes or normal controls exhibited
      a significant difference between VA under the fast and slow conditions. We
      further compared the "temporal crowding" measure to two measures of spatial
      crowding: (1) static Tumbling-E acuity in multi-pattern crowded displays (N=26)
      and (2) Gabor alignment with lateral flankers (N=20). We found that all three
      measures of crowding (one temporal and two spatial) were highly correlated across
      subjects while being largely independent of the visual acuity for a single
      isolated pattern, with both spatial and temporal crowding being high and
      correlated in strabismus and low in anisometropia. This suggests that time and
      space are related in crowding, at least in amblyopia.

PMID- 17502116
TI  - A systematic literature review of the clinical and cost-effectiveness of hadron
      therapy in cancer.
AB  - BACKGROUND: In view of the continued increase in the number of hadron (i.e.
      neutron, proton and light or heavy ion) therapy (HT) centres we performed a
      systematic literature review to identify reports of the efficacy of HT. METHODS:
      Eleven databases were searched systematically. No limit was applied to language
      or study design. Established experts were contacted for unpublished data. Data on
      outcomes were extracted and summarised in tabular form. RESULTS: Seven hundred
      and seventy three papers were identified. For proton and heavy ion therapy, the
      number of RCTs was too small to draw firm conclusions. Based on prospective and
      retrospective studies, proton irradiation emerges as the treatment of choice for
      some ocular and skull base tumours. For prostate cancer, the results were
      comparable with those from the best photon therapy series. Heavy ion therapy is
      still in an experimental phase. CONCLUSION: Existing data do not suggest that the
      rapid expansion of HT as a major treatment modality would be appropriate. Further
      research into the clinical and cost-effectiveness of HT is needed. The formation
      of a European Hadron Therapy Register would offer a straightforward way of
      accelerating the rate at which we obtain high-quality evidence that could be used
      in assessing the role of HT in the management of cancer.

PMID- 17502117
TI  - Effect of increase of radiation dose on local control relates to pre-treatment
      FDG uptake in FaDu tumours in nude mice.
AB  - OBJECTIVES: To investigate whether heterogeneity in [(18)F]2-fluoro-2-deoxy-d
      glucose (FDG) uptake in a single tumour line, i.e. in tumours with identical
      genetic background, relates to radiation response. MATERIALS AND METHODS: Sixty
      two human FaDu head and neck squamous cell carcinomas in nude mice with a
      diameter of 7mm entered the study. FDG-PET scanning was performed without
      anaesthesia on an animal PET scanner immediately prior to irradiation in order to
      determine maximum standardized uptake values (SUV(max)). Single dose irradiations
      of 25 or 35Gy were applied under normal blood flow conditions using 200kV X-rays
      (0.5mm Cu, approximately 1.2Gy min(-1)). The mice were observed for 120 days
      after irradiation, experimental endpoint was local tumour control evaluated using
      the Kaplan-Meier method. RESULTS: Analyzing all 62 animals, tumour control
      probability after irradiation with 25Gy was significantly lower than after
      irradiation with 35Gy (29% vs. 57%, log rank p=0.016). Pre-treatment SUV(max)
      values ranged from 0.72 to 3.47, the median SUV(max) value was 1.59. In tumours
      with FDG uptake less than the median SUV(max), local control was 37% after 25Gy
      vs. 47% after 35Gy (p=0.37). In contrast, substantial differences in local tumour
      control were found in tumours with FDG uptake above the median SUV(max) (24% vs.
      71%, p=0.006). Multivariate Cox analysis revealed a significant decrease of
      hazard of recurrence with increasing dose and SUV(max). CONCLUSIONS: An increase
      of radiation dose had a greater effect on local control in FaDu tumours with
      higher FDG uptake than in tumours with lower FDG uptake. This supports the
      hypothesis that pre-treatment FDG-PET may provide useful information for
      heterogeneous radiation dose prescription in subvolumes of tumours of individual
      patients. As only one tumour model was studied and single doses were applied,
      confirmatory investigations using further tumour models and fractionated
      radiotherapy are warranted.

PMID- 17502118
TI  - EGFR-targeted anti-cancer drugs in radiotherapy: preclinical evaluation of
      mechanisms.
AB  - Preclinical and clinical results indicate that the EGFR can mediate
      radioresistance in different solid human tumours. Combination of radiotherapy and
      EGFR inhibitors can improve local tumour control compared to irradiation alone
      and has been introduced into clinical radiotherapy practice. So far several
      mechanisms have been identified in preclinical studies to contribute to improved
      local tumour control after radiation combined with EGFR inhibitors. These include
      direct kill of cancer stem cells by EGFR inhibitors, cellular radiosensitization
      through modified signal transduction, inhibition of repair of DNA damage, reduced
      repopulation and improved reoxygenation during fractionated radiotherapy. Effects
      and mechanisms may differ for different classes of EGFR inhibitors, for different
      tumours and for normal tissues. The mechanisms underlying this heterogeneity are
      currently poorly understood, and predictive assays are not available yet.
      Importantly, mechanisms and predictors for the combined effects of radiation with
      EGFR inhibitors appear to be considerably different to those for application of
      EGFR inhibitors alone or in combination with chemotherapy. Therefore to further
      evaluate the efficacy and mechanisms of EGFR-inhibition in combined treatments,
      radiotherapy-specific preclinical research strategies, which include in vivo
      experiments using local tumour control as an endpoint, as well as animal studies
      on normal tissue toxicity are needed.

PMID- 17502119
TI  - ATM missense variant P1054R predisposes to prostate cancer.
AB  - BACKGROUND: Prostate cancer is associated with defective DNA strand break repair
      after DNA damage leading to genetic instability and prostate cancer progression.
      The ATM (ataxia-telangiectasia mutated) gene product is known to play an
      important role in cell cycle regulation and maintenance of genomic integrity. We
      investigated whether the prevalence of the ATM missense substitution P1054R is
      increased in a hospital-based series of prostate cancer patients and whether
      carriers are at increased risk for treatment-related side effects. MATERIALS AND
      METHODS: A consecutive series of 261 patients treated for early-stage prostate
      cancer with I-125 brachytherapy (permanent seed implantation) between 10/2000 and
      04/2006 at our institution and a comparison group of 460 male control individuals
      were screened for the presence of the P1054R variant. Outcome of therapy
      regarding morbidity was assessed prospectively and compared between carriers vs.
      non-carriers with the International Prostate Symptom Score (IPSS), a Quality-of
      Life-index (QoL) and the International Index of Erectile Function (IIEF-15) with
      its subgroups (IIEF-5 and EF). RESULTS: The proportion of carriers of the P1054R
      variant was significantly higher among prostate cancer patients than in the
      general population (25 out of 261 vs. 22 out of 460; OR 2.1; 95% CI 1.2-3.8,
      p<0.01). A subgroup of the carriers additionally harboured the ATM missense
      variant F858L that was associated with a similar risk (OR=2.2; 95% CI 1.1-4.6;
      p=0.03). After a mean follow-up of 18 months there were no statistically
      significant differences regarding IPSS (p=0.48), QoL (p=0.61), IIEF-15 score
      (p=0.78), IIEF-5 score (p=0.83), and EF score (p=0.80), respectively.
      CONCLUSIONS: The ATM missense variant P1054R confers an about twofold increased
      risk for prostate cancer in our series. The subgroup of patients with the second
      site variant F858L is not at significantly higher risk. After 18 months, there
      was no evidence for an increased adverse radiotherapy response in P1054R
      carriers.

PMID- 17502120
TI  - Imaging the hypoxia surrogate marker CA IX requires expression and catalytic
      activity for binding fluorescent sulfonamide inhibitors.
AB  - BACKGROUND AND PURPOSE: Carbonic anhydrase (CA) IX expression is increased in
      response to hypoxia. Recently, sulfonamide based carbonic anhydrase inhibitors
      (CAI) showing specificity for CA IX have been designed. Aim was to investigate
      the CAI binding properties under normoxia, hypoxia and reoxygenation. MATERIAL
      AND METHODS: Cells with varying CA IX expression were incubated with fluorescein
      labeled CAI (1mM) during normoxia, hypoxia (0.2%) and reoxygenation. CA IX
      expression levels were assessed using Western blotting. CAI binding was
      determined by immunostaining and flow cytometry. RESULTS: CAI binding in hypoxic
      cells was significantly higher compared with normoxic cells and correlated with
      upregulated CA IX levels. Binding occurred within 15min of hypoxia, but was
      gradually lost upon reoxygenation. Interestingly, although CA IX levels remained
      high upon reoxygenation, CAI binding was dramatically reduced and no longer
      correlated with CA IX expression. Similarly, RCC4 cells, constitutively
      expressing CA IX, do not bind CAI under normoxic conditions. CONCLUSIONS: Our
      results confirm and extend previous results showing that CAI binding occurs only
      under hypoxia. The inability of CAI to bind CA IX in RCC4 cells and following
      reoxygenation in other cells demonstrates that formation of the active site not
      only depends on HIF-1alpha-dependent gene activity, but also on the absence of
      oxygen per se.

PMID- 17502121
TI  - Enhanced parameter estimation methods for noisy SPECT data.
AB  - Functional imaging with PET and SPECT is capable of visualizing subtle changes in
      physiological function in vivo, which aids in the early diagnosis of disease.
      Quantitative functional parameters are usually derived by curve fitting the
      dynamic data of a functional imaging study. However, the intrinsic high level of
      noise and low signal to noise ratio can lead to instability in the parameter
      estimation and give rise to non-physiological parameter estimates. Clustering
      techniques have been applied to improve signal to noise ratio and the reliability
      of parametric image generation, but these may enhance partial volume effects
      (PVE) and result in biased estimates for small structures. Therefore, a
      systematic study was performed using computer simulations of SPECT data and the
      generalized linear least square algorithm (GLLS) to evaluate the ability of three
      proposed enhanced methods and a clustering-aided method to improve the
      reliability of parametric image generation. The results demonstrate that
      clustering with sufficient cluster numbers ameliorated PVE and provided noise
      insensitive parameter estimates. The enhanced GLLS method with a prior volume of
      distribution and bootstrap Monte Carlo resampling improved the reliability of the
      curve fitting, and is thus suitable for application to noisy SPECT data.

PMID- 17502122
TI  - Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties
      of pyrrolo[3,4-a]carbazole-1,3-diones, pyrrolo[3,4-c]carbazole-1,3-diones, and 2
      aminopyridazino[3,4-a]pyrrolo[3,4-c]carbazole-1,3,4,7-tetraone.
AB  - The synthesis of substituted pyrrolo[3,4-a]carbazole-1,3-diones, pyrrolo[3,4
      c]carbazole-1,3-diones, and 2-aminopyridazino[3,4-a]pyrrolo[3,4-c]carbazole
      1,3,4,7-tetraone is reported. Their inhibitory properties toward Checkpoint 1
      kinase (Chk1) have been evaluated and their in vitro antiproliferative activities
      toward three tumor cell lines: murine leukemia L1210, human colon carcinoma HT29
      and HCT116 have been determined. From the biological results, it appears that, in
      contrast with the upper E heterocycle, the lower D heterocycle is not absolutely
      required for Chk1 inhibition. The ATP binding pocket of Chk1 seems to be
      adaptable to substitution of the nitrogen of the imide E heterocycle with a
      hydroxymethyl group, allowing the fundamental hydrogen bond with the Glu(85)
      residue of the enzyme.

PMID- 17502123
TI  - Evaluation of functional relationships for predicting mainstream smoke
      constituent machine yields for conventional cigarettes from the Japanese market.
AB  - The objective of this study was to predict mainstream smoke constituent yields
      for conventional filter cigarette brands on sale in Japan between 2004 and 2005.
      Mainstream smoke was generated under ISO machine smoking conditions. Developed
      functional relationships indicate the validity of benchmarking even for a market
      which is characterized by a diversity of tobacco blend types. Smoke yields were
      in general well predicted by linear regression with "tar" (R2>or=0.7). Blend-type
      sensitive analytes like tobacco-specific nitrosamines showed improved prediction
      relationships after blend stratification or regressing against nitric oxide (NO,
      R(2)>0.7). Relationships calculated from 83 exploratory brands were validated
      with a subset of 23 validation brands. Seventy-five to one-hundred percent of the
      validation brand yields were inside the 95% prediction intervals. The mean
      relative prediction error over all analytes was 24% after stratification. Smoke
      constituents yields analyzed in 2002 from 96 Japanese market products were well
      predicted and indicate the model validity over time. Similar relationships were
      observed when comparing American blended filter cigarette yields from Japan and
      worldwide markets. Consistent with reported results from previous benchmark
      studies and market surveys mainstream smoke constituent yields are well
      predictable when "tar" (and NO) yields are known.

PMID- 17502124
TI  - Preclinical evaluation of YC-1, a HIF inhibitor, for the prevention of tumor
      spreading.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is believed to promote tumor growth,
      and thus, is viewed as one of the most compelling cancer therapy targets. YC-1 is
      widely used as a potent inhibitor of HIF-1alpha both in vitro and in vivo, and is
      also being developed as a novel anticancer drug. However, little is known about
      the effects of YC-1 on tumor invasion or metastasis. In the present study, we
      found that the Hep3B cell migration-stimulatory effect of hypoxia was abolished
      by HIF-1alpha siRNA or YC-1. YC-1 also significantly inhibited the migrations of
      other cancer cells. Furthermore, YC-1 effectively inhibited cell invasion through
      Matrigel. In nude mice, GFP-expressing stable cell-lines of Hep3B or H1299 were
      inoculated into spleens to induce liver metastasis or into the pleural cavity to
      induce lung invasion. In untreated mice, many tumor lesions emitting strong
      fluorescence were found in livers or lungs, and fluorescence intensities and
      tumor lesion numbers were markedly reduced in YC-1-treated mice. These results
      suggest that YC-1 effectively inhibits tumor invasion and metastasis, and imply
      that YC-1 is worth while to further develop as a multipurpose anticancer drug.

PMID- 17502125
TI  - Aerobic degradation of technical hexachlorocyclohexane by a defined microbial
      consortium.
AB  - Organochlorine pesticides including hexachlorocyclohexane (HCH) and
      dichlorodiphenyltrichloroethane (DDT) are largely used in developing countries
      like India for public health and agricultural purposes. Even though the
      agricultural use of technical mixture (tech-HCH) is banned, countries like India
      are still using gamma-HCH for economic purposes. Thus, in addition to already
      contaminated sites, new sites are being contaminated with gamma-HCH and its
      stereoisomers. In the environment, these isomers have a half-life of 8-10 years.
      In our laboratory, we developed a microbial consortium capable of degrading tech
      HCH. Conditions such as induction, inoculum level, concentration of the
      substrate, pH of degradation and interaction between isomers were optimized for
      tech-HCH degradation. Up to 25 ppm tech-HCH was degraded at an inoculum level of
      100 microg protein/mL, pH 7.5 at ambient temperature (26-28 degrees C). The
      degradation of HCH-isomers was in the order of gamma>alpha>beta>delta. The rate
      of degradation was also determined.

PMID- 17502126
TI  - Of PCSK9, cholesterol homeostasis and parasitic infections: possible survival
      benefits of loss-of-function PCSK9 genetic polymorphisms.
AB  - Cholesterol is important for cell membrane structure and functions as well as for
      production of steroid hormones and bile acids. It is transported through the body
      as lipoprotein particles of varying density and composition. Cholesterol
      homeostasis is maintained through finely tuned mechanisms regulating dietary
      uptake, hepatic biosynthesis and secretion as well as plasma clearance.
      Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cellular uptake of
      plasma low-density lipoprotein-cholesterol (LDL-C) by promoting LDL receptor
      (LDLR) degradation. Two nonsense single-nucleotide polymorphisms (SNPs) at the
      PCSK9 locus have been associated with life-long hypocholesterolemia and a
      remarkable reduction of the risk for coronary heart disease (CHD) in African
      Americans. These loss-of-function SNPs presumably render PCSK9 less capable of
      inducing LDLR catabolism, effectively increasing LDLR availability and allowing
      efficient removal of plasma LDL-C. The combined frequency of heterozygosity for
      these nonsense SNPs is approximately 3-4% in populations of African descent.
      Homozygosity for either SNP, which would aggravate hypocholesterolemia, is
      reportedly rare. Whether such an aggravation would represent a health risk is
      still a matter of debate. From an evolutionary point of view, the
      cardioprotective effect of these nonsense SNPs may be a secondary phenotype made
      evident by the dyslipidemia-inducing lifestyle of today's North America. Their
      relatively high frequency in African-Americans must be interpreted in the context
      of the ancestral environment of these subjects in Africa, where diet and
      lifestyle were presumably less predisposing to atherosclerosis and where
      parasitic infections were major causes of morbidity and mortality before
      reproductive age. Parasites feed on host cholesterol for successful infection.
      The nonsense PCSK9 SNPs may have been positively selected because they reduced
      susceptibility to severe parasitic infections through cholesterol restriction. If
      so, these SNPs should be significantly more frequent in Sub-Saharan Africa where
      parasitic diseases, malaria in particular, have been and still are major
      selective forces.

PMID- 17502127
TI  - The role of endothelial dysfunction in the pathogenesis of impaired diabetic
      wound healing: a novel therapeutic target?
AB  - The global burden of diabetes is attributed to its multiple associated
      complications including impaired wound healing which can ultimately result in
      amputation. Peripheral vascular disease, infection, neuropathy and abnormal local
      cellular and cytokine activity are some of the traditionally cited pathological
      instigators of defective diabetic wound repair. Despite intensive research and
      subsequent advances in diabetic wound care technology a single treatment with
      measurable clinical impact has yet to be determined. The phenomenon of
      endothelial dysfunction as seen in atherosclerosis and recently identified as a
      characteristic of diabetic vasculature may contribute to impaired cutaneous
      healing in this group. Indicators of endothelial dysfunction have been
      demonstrated in diabetic wounds by a number of investigators. Successful results
      are being obtained with modifiers of endothelial function in the management of
      cardiovascular disease. We hypothesise that endothelial dysfunction plays a
      substantial contributory role in the pathogenesis of wound healing impairment of
      diabetes and holds potential as a target for therapeutic intervention.

PMID- 17502128
TI  - A two-phase strategy for treatment of oxidant-dependent cancers.
AB  - In many cancers, a chronic increase in oxidant stress - associated with elevated
      levels of hydrogen peroxide - contributes to the increased proliferative rate,
      diminished apoptosis, increased angiogenic and metastatic capacity, and
      chemoresistance that often characterize advanced malignancies. This oxidant
      stress often reflects up-regulation of expression and activity of NADPH oxidase,
      and/or decreased activity of catalase, which functions as suppressor gene in
      oxidant-dependent cancers. These characteristics of oxidant-dependent cancers
      suggest a dual strategy for treatment of these cancers. Since ascorbate can react
      spontaneously with molecular oxygen to generate hydrogen peroxide, high-dose
      intravenous ascorbate should be selectively toxic to tumors that are low in
      catalase activity - as suggested by numerous cell culture studies. Measures which
      concurrently improve the oxygenation of hypoxic tumor regions would be expected
      to boost the efficacy of such therapy; calcitriol and high-dose selenium might
      also be useful in this regard. Secondly, during the intervals between sessions of
      ascorbate therapy, administration of agents which can safely inhibit NADPH
      oxidase would be expected to slow the proliferation and spread of surviving tumor
      cells - while providing selection pressure for a further decline in catalase
      activity. In effect, cancers treated in this way would be whipsawed between
      lethally excessive and inadequately low oxidant stress. An additional possibility
      is that ascorbate-induced oxidant stress in tumors might potentiate the cell kill
      achieved with concurrently administered cytotoxic drugs, inasmuch as oxidant
      mechanisms appear to play a mediating role in the apoptosis induced by many such
      drugs, largely via activation of c-Jun NH(2)-terminal kinase; cell culture
      studies would be useful for evaluating this possibility.

PMID- 17502129
TI  - The incoherence hypothesis of schizophrenia: based on decomposed oligodendrocyte
      axonic relations.
AB  - Based on the findings of white matter abnormalities in brains with schizophrenia,
      it is hypothesized that this disorder may be responsible for symptoms of
      incoherence of schizophrenia. It is supposed that the processes of
      oligodendrocytes tie the various properties of axonic information conductance
      together into categories. For this oligodendrocytic computation capacity a
      formalism is proposed. In the case of a decrease or loss of oligodendroglia, a
      brain with schizophrenia is unable to categorize information processing, so that
      on a behavioral level symptoms of incoherence (thought disorder, etc.) occur.
      Similarities and differences in the pathophysiology of multiple sclerosis and
      schizophrenia are also shortly discussed. Together, a decomposition of the
      oligodendrocyte-axonic system may be responsible for symptoms of incoherence in
      schizophrenia.

PMID- 17502130
TI  - Combined effects of iontophoretic and chemical enhancement on drug delivery. II.
      Transport across human and murine skin.
AB  - This paper reports measurements of the release characteristics of the model drug
      salbutamol from a liquid crystalline vehicle across both human and hairless
      murine skin in vitro. The use of oleic acid and iontophoresis as penetration
      enhancement techniques, used separately and simultaneously, was also
      investigated. Over a period of 12h, salbutamol base did not diffuse from the
      vehicle across excised human skin while, in contrast, over a period of 2h, the
      drug passively transported across hairless murine skin. The diffusion co
      efficient for the drug in this tissue was estimated to be 4.54+/-0.60x10(
      9)cm(2)s(-1) with a permeability co-efficient of 7.03+/-0.83x10(-7)cms(-1). A
      current of density of 0.39mAcm(-2) facilitated a significant transport of
      salbutamol from the liquid crystalline vehicle across excised human skin but with
      a small (<0.1) transport number. The quantity of salbutamol transported across
      excised hairless murine skin under the same conditions was significantly greater
      with a transport number of 0.68. The alteration of the permeability of the tissue
      was less than that of the human skin and a full recovery of the pre-iontophoretic
      permeability of murine skin was consistently observed. The incorporation of
      either oleic or lauric acid into the monoglyceride component of the vehicle at a
      concentration of 0.1M had a marked effect on the transport of salbutamol across
      both human and murine skin. The initial passive permeation of the drug across the
      skin was not affected but the rate of drug delivery during iontophoresis was
      typically observed to increase by a factor greater than two. The post
      iontophoretic transport of salbutamol across either tissue was also substantially
      enhanced in the presence of the fatty acid. The analogous use of stearic acid did
      not significantly influence the iontophoretic or the post-iontophoretic transport
      of salbutamol across excised human skin. The investigation also revealed a
      synergistic combination of the fatty acid and anodal iontophoresis to enhance the
      in vitro transport of other drug substances, including nicotine and diltiazem
      hydrochloride across murine skin. Oleic acid increased both the iontophoretic and
      post-iontophoretic transport of nicotine, so that the enhancement of drug
      delivery was greater than that caused by the current alone. The investigation
      also indicated that the barrier properties of the skin recover following the
      constant current iontophoresis in the presence of oleic or lauric acids.

PMID- 17502131
TI  - Biological characteristics and behaviour of putatively curatively resected
      colorectal liver metastases.
AB  - AIM: To identify whether positive resection margin tumours had a more aggressive
      phenotype, using tumour micro-vessel density and invasive margin. METHODS:
      Archival tissue was retrieved from 109 patients who had undergone resection for
      colorectal liver metastases. The nature of the invasive margin was determined by
      H&E histochemistry. MVD was visualised using immunohistochemical detection of
      CD31 antigen and quantified using image capture computer software. Clinical
      details and outcome were retrieved and collated with invasive margin and MVD data
      in a statistical database. RESULTS: 41/68 patients with a positive resection
      margin (R1) had recurrences following liver resection, while only 16/41 patients
      with a clear margin (R0) developed recurrences. More of the margin clear patients
      also developed capsulated liver metastases (56%), compared to positive resection
      margin patients (22%) (Chi squared test p<0.001). The stromal margin MVD in the
      R0 patients was 250 (11-609), compared to the R1 value of 122 (27-428) (Mann
      Whitney U test p=0.01). DISCUSSION: Positive resection margin, amongst other
      factors, is a predictor of poor prognosis. This appears to be in part explained
      by the expression of adverse tumour characteristics.

PMID- 17502132
TI  - Effect of neoadjuvant epirubicin and total androgen blockade on complete
      pathological response in patients with clinical stage T3/T4 prostate cancer.
AB  - AIMS: Most patients with stage T3-T4 prostate cancer experience disease relapse
      despite radiation and/or hormonal therapy, and their management remains
      controversial. We investigated the feasibility of, and the pathological response
      induced by neoadjuvant chemo-hormonal treatment in men with clinical stage T3/T4.
      METHODS: Fifteen patients underwent neoadjuvant therapy consisting of weekly
      intravenous infusions of epirubicin 30mg/m(2) and total androgen blockade (TAB)
      for three months before undergoing radical prostatectomy, after which all
      received locoregional conformal radiotherapy (66Gy) and then continued with TAB
      and three additional months of epirubicin. RESULTS: After neoadjuvant therapy,
      PSA levels decreased in all 15 patients and became undetectable in two. None of
      the patients achieved a complete pathological response, but a 35-75% reduction in
      tumour size was observed in all cases, and all the patients were able to undergo
      successful prostatectomy. Pathological assessments of the surgical specimens
      revealed negative margins in 13 patients. After a median follow-up of 34 months
      (range 11-62), 14 patients (93%) are still clinically and biochemically disease
      free. No grade 3 or 4 complications occurred. CONCLUSION: This study suggests
      that neoadjuvant treatment with epirubicin and TAB is feasible and well tolerated
      in patients with clinical stage T3-T4 prostate cancer.

PMID- 17502133
TI  - Simultaneous carotid endarterectomy and coronary artery bypass grafting: results
      in specific patient groups.
AB  - We examined the safety of performing synchronous carotid endarterectomy (CEA) and
      coronary artery bypass grafting (CABG) in specific groups of patients with
      coexistent cerebral and coronary vascular disease. Between 1981 and 2003, 8,277
      patients who underwent CABG in our institution had noninvasive screening for
      carotid disease. Two hundred seventy-seven (3.34%) patients were found to have
      severe (>70%) carotid stenosis. This patient population was divided into three
      subgroups: group A had unilateral carotid disease (n = 200), group B had
      bilateral carotid disease (n = 55), and group C had contralateral carotid
      occlusion (n = 22). In 29 patients (10.4%), the carotid disease was symptomatic.
      A simultaneous CABG and CEA was performed in all three subgroups. Patients in
      group B underwent initially repair of the most dominant lesion, soon followed by
      contralateral CEA. Patients who underwent only CABG (n = 8,000) served as
      controls. Overall combined hospital mortality regardless of etiology for the
      combined group was 3.61% vs. 1.7% for the patients who had CABG only (P > 0.1).
      The stroke and/or myocardial infarction-associated mortality for the simultaneous
      CEA-CABG group was 2.52%. There were six deaths in group A (3%), two in group B
      (3.6%), and two in group C (9.09%). Early stroke complicated the course of four
      (2%) patients in group A, one (1.8%) patient in group B, and three (13.64%)
      patients in group C compared to a stroke rate of 1.28% in controls. Overall
      stroke rate in the combined group was 2.8%. History of previous stroke and age 70
      80 were the most important predictors of postoperative stroke and death. In the
      combined surgery group, the postoperative myocardial infarction rate was 0.72%
      vs. 0.58% in the control group. The mean length of hospital stay was 9 days for
      patients who had the combined procedure vs. 8.1 days for patients who had CABG
      only. Use of the combined procedure for patients with concomitant carotid and
      coronary artery disease was justified in the patients under study.

PMID- 17502134
TI  - Physico-chemical and microbiological analyses of fermented corn cob, rice bran
      and cowpea husk for use in composite rabbit feed.
AB  - An experiment was conducted to evaluate the effect of fermentation on the
      proximate composition of corn cob, rice bran and cowpea husk for use in composite
      rabbit feed formulations. The test ingredients were moistened with tap water and
      allowed to ferment naturally at room temperature. During fermentation, samples of
      the fermenting materials were extracted at zero, 24 and 48 h for physico-chemical
      and microbiological analyses using standard procedures. The microorganisms
      associated with the fermenting materials were identified as Rhizopus oligosporus,
      Aspergillus oryzae, Aspergillus niger, Rhodotorula, Geotrichum candidum, Candida
      albicans, and Saccharomyces cerevisiae. Two (R. oligosporus and S. cerevisiae)
      out of microorganisms present were used as starter cultures to ferment the test
      ingredients and the fermented products were then analyzed. From the results
      obtained S. cerevisiae enhanced the protein and fat contents while R. oligosporus
      was able to degrade the fiber significantly.

PMID- 17502135
TI  - Polycyclic aromatic hydrocarbons and phthalic acid esters in the soil-radish
      (Raphanus sativus) system with sewage sludge and compost application.
AB  - We studied the accumulation of polycyclic aromatic hydrocarbons (PAHs) and
      phthalic acid esters (PAEs) in a latosolic red soil and radish (Raphanus sativus)
      with application of sewage sludge at rates of 10, 20 and 40 g kg(-1) soil or
      compost at rate of 10 g kg(-1) soil. In radish the concentrations of individual
      PAHs and PAEs varied from non-detectable to 803 microg kg(-1) dry weight (d.w.)
      and from non-detectable to 2048 microg kg(-1) d.w., respectively. Compared to the
      control, higher application rates of sewage sludge resulted in pronounced
      increases in shoot, root and soil concentrations of PAHs and PAEs. PAE
      concentrations in radish grown in soil spiked with sludge compost were higher
      while the PAH concentrations were comparable to those receiving 10 g kg(-1) of
      sewage sludge. However, the root biomass of radish in soil amended with compost
      was significantly higher and the shoot-to-root ratio was significantly lower than
      in the other treatments. The bioconcentration factors (BCFs, the ratio of
      contaminant concentration in plant tissue to the soil concentration) of di-n
      butyl phthalate and di(2-ethylhexyl) phthalate in both shoots and roots and of
      total PAH concentrations in roots were less than 1.0, but some BCFs for
      individual PAHs were high with a maximum value of 80.

PMID- 17502136
TI  - Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding
      protein (aFABP).
AB  - Herein we report the first disclosure of biphenyl azoles that are nanomolar
      binders of adipocyte fatty acid binding protein (aFABP or aP2) with up to
      thousand-fold selectivity against muscle fatty acid binding protein and epidermal
      fatty acid binding protein. In addition a new radio-ligand to determine binding
      against the three fatty acid binding proteins was also synthesized.

PMID- 17502137
TI  - Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3
      methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796):
      a gamma-secretase inhibitor with Abeta lowering activity in a transgenic mouse
      model of Alzheimer's disease.
AB  - We report on the design of benzodiazepinones as peptidomimetics at the carboxy
      terminus of hydroxyamides. Structure-activity relationships of diazepinones were
      investigated and orally active gamma-secretase inhibitors were synthesized.
      Active metabolites contributing to Abeta reduction were identified by analysis of
      plasma samples from Tg2576 mice. In particular, (S)-2-((S)-2-(3,5-difluorophenyl)
      2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin
      5-yl)propanamide (BMS-433796) was identified with an acceptable pharmacodynamic
      and pharmacokinetic profile. Chronic dosing of BMS-433796 in Tg2576 mice
      suggested a narrow therapeutic window and Notch-mediated toxicity at higher
      doses.

PMID- 17502138
TI  - RNAi gene silencing using cerasome as a viral-size siRNA-carrier free from fusion
      and cross-linking.
AB  - Surface-rigidified cerasomes (ceramic-coated liposomes) are neither fused nor
      cross-linked when bound to siRNA (short duplex RNA) but not to plasmid DNA (long
      duplex DNA) which induces cross-linking. Non-ceramic reference liposomes are
      easily fused by the siRNA. The cerasome can thus be used as a viral-size siRNA
      carrier in a wide range of concentration for RNAi silencing of exogenous and
      endogenous genes.

PMID- 17502139
TI  - Radioiodinated aza-diphenylacetylenes as potential SPECT imaging agents for beta
      amyloid plaque detection.
AB  - Two new iodinated fluoro- and hydroxy-pegylated aza-diphenylacetylene
      derivatives, 1 and 2, targeting beta-amyloid (Abeta) plaques have been
      successfully prepared. In vitro binding carried out in tissue homogenates
      prepared from postmortem AD brains with [(125)I]IMPY (6-iodo-2-(4'
      dimethylamino)phenyl-imidazo[1,2-a]pyridine) as the radioligand indicated good
      binding affinities (K(i)=9.2 and 16.8 nM for 1 and 2, respectively). Brain
      penetrations of the corresponding radioiodinated ligands, evaluated in the normal
      mice, showed good initial brain penetrations (3.55% and 5.67% ID/g for [(125)I]1
      and [(125)I]2 at 2 min post-injection). The washout from normal mice brain was
      relatively fast (0.33% and 0.91% ID/g at 2h post-injection). The specific binding
      of these radioiodinated ligands to beta-amyloid plaques was clearly demonstrated
      using film autoradiography of AD brain sections. Taken together, these
      preliminary results strongly suggest that these novel iodinated aza
      diphenylacetylenes may be potentially useful for imaging Abeta plaques in the
      living human brain.

PMID- 17502141
TI  - Modeling assisted rational design of novel, potent, and selective
      pyrrolopyrimidine DPP-4 inhibitors.
AB  - Molecular modeling was used to improve potency of the cyclohexylamine series. In
      addition, a 3-D QSAR method was used to gain insight for reducing off-target DPP
      8/9 activities. Compounds 3, 4, and 5 were synthesized and found to be potent DPP
      4 inhibitors, in particular 4 and 5 are designed to be highly selective against
      off-target DASH enzymes while maintaining potency on DPP-4.

PMID- 17502140
TI  - Synthesis and biodistribution of 8-iodo-11-(4-methylpiperazino)-5H
      dibenzo[b,e][1,4]-diazepine: Iozapine.
AB  - 8-Iodo-11-(4-methylpiperazino)-5H-dibenzo[b,e][1,4]-diazepine: Iozapine, a
      potential D(4)-receptor ligand was synthesized using oxidative iodo
      destannylation reaction. The preliminary biodistribution studies of
      radioiodinated iozapine have shown that the compound is taken up in the brains of
      mice and rabbits.

PMID- 17502142
TI  - Synthesis and antibacterial activity of 3-keto-6-O-carbamoyl-11,12-cyclic
      thiocarbamate erythromycin A derivatives.
AB  - A series of 3-keto-6-O-carbamoyl-11,12-cyclic thiocarbamate erythromycin A
      derivatives has been synthesized. The best compounds in this series possess
      potent in vitro antibacterial activity against erythromycin-susceptible and
      erythromycin-resistant bacteria.

PMID- 17502143
TI  - Design and synthesis of benzoazepinone-derived cyclic malonamides and aminoamides
      as potent gamma-secretase inhibitors.
AB  - We report the synthesis of benzoazepine-derived cyclic malonamides (2) and
      aminoamides (3) as gamma-secretase inhibitors for the potential treatment of
      Alzheimer's disease. The in vitro structure-activity relationships of 2 and 3
      along with dog pharmacokinetic results are described.

PMID- 17502144
TI  - The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta
      kinases.
AB  - A potent and selective series of 2-amino-3,5-diarylbenzamide inhibitors of IKK
      alpha and IKK-beta is described. The most potent compounds are 8h, 8r and 8v,
      with IKK-beta inhibitory potencies of pIC(50) 7.0, 6.8 and 6.8, respectively. The
      series has excellent selectivity, both within the IKK family over IKK-epsilon,
      and across a wide variety of kinase assays. The potency of 8h in the IKK-beta
      enzyme assay translates to significant cellular activity (pIC(50) 5.7-6.1) in
      assays of functional and mechanistic relevance.

PMID- 17502145
TI  - Inhibition of IGF-1R and lipoxygenase by nordihydroguaiaretic acid (NDGA)
      analogs.
AB  - Herein, we pursue the hypothesis that the structure of nordihydroguaiaretic acid
      (NDGA) can be refined for selective potency against the insulin-like growth
      factor 1 receptor (IGF-1R) as a potential therapeutic target for breast cancer
      while diminishing its action against other cellular targets. Thus, a set of NDGA
      analogs (7a-7h) was prepared and examined for inhibitory potency against IGF-1R
      kinase and an alternative target, 15-lipoxygenase (15 LOX). The anti-cancer
      effects of these compounds were determined by their ability to inhibit IGF-1
      mediated cell growth of MCF-7 breast cancer cells. The design of the analogs was
      based upon a cursory Topliss approach in which one of NDGA's aromatic rings was
      modified with various substituents. Structural modification of one of the two
      catechol rings of NDGA was found to have little effect upon the inhibitory
      potency against both kinase activity of the IGF-1R and IGF-1 mediated cell growth
      of MCF-7 cells. 15-LOX was found to be most sensitive to structural modifications
      of NDGA. From the limited series of NDGA analogs examined, the compound that
      exhibited the greatest selectivity for IGF-1 mediated growth compared to 15-LOX
      inhibition was a cyclic analog 7h with a framework similar to a natural product
      isolated from Larrea divaricata. The results for 7h are significant because while
      NDGA displays biological promiscuity, 7h exhibits greater specificity toward the
      breast cancer target IGF-1R with that added benefit of possessing a 10-fold
      weaker potency against 15-LOX, an enzyme which has a purported tumor suppressing
      role in breast cancer. With increased specificity and potency, 7h may serve as a
      new lead in developing novel therapeutic agents for breast cancer.

PMID- 17502147
TI  - 19F NMR detection of the complex between amantadine and the receptor portion of
      the influenza A M2 ion channel in DPC micelles.
AB  - (19)F NMR probes were used to follow interactions between ligands in the
      aminoadamantane series, amantadine (Am) 1 and 3-F-Am 2, and the 5-F-Trp20
      transmembrane fragment of the influenza A M2 proton channel (F-M2TM 3) in
      dodecylphosphocholine micelles over the pH range 5-8. Above pH 7, when the
      peptide adopts a tetrameric state that is able to bind channel blocking ligands,
      (19)F-Trp signals from both the free and bound states of the M2TM tetramer are
      resolved. This differentiation of bound and unbound states of the M2TM receptor
      by (19)F NMR may provide a system for SAR studies.

PMID- 17502146
TI  - Synthesis and antibacterial activity of 5-deoxy-5-episubstituted arbekacin
      derivatives.
AB  - 5-Deoxy-5-episubstituted arbekacin derivatives have been designed and efficiently
      synthesized. The synthetic compounds showed potent antibacterial activity against
      both Staphylococcus aureus, including methicillin-resistant S. aureus, and
      Pseudomonas aeruginosa. In particular, these derivatives were superior to
      arbekacin against MRSA strains expressing the bifunctional aminoglycoside
      modifying enzyme AAC(6')-APH(2''). The antibacterial activity of the 5-deoxy-5
      episubstituted arbekacin derivatives against Pseudomonas aeruginosa was markedly
      influenced by the efflux system of MexXY/OprM. The 6'-N-methyl derivative of the
      5-epi arbekacin was effective against Pseudomonas aeruginosa expressing the
      aminoglycoside-modifying enzyme AAC(6').

PMID- 17502148
TI  - Discovery of structurally diverse HIV-1 integrase inhibitors based on a chalcone
      pharmacophore.
AB  - Recently, we reported small-molecule chalcones as a novel class of HIV-1
      integrase (IN) inhibitors. The most potent compound showed an IC50 value of 2
      microM for both IN-mediated 3'-processing and strand transfer reactions. To
      further utilize the chalcones, we developed pharmacophore models to identify
      chemical signatures important for biological activity. The derived models were
      validated with a collection of published inhibitors, and then were applied to
      screen a subset of our small molecule database. We tested 71 compounds in an in
      vitro assay specific for IN enzymatic activity. Forty-four compounds showed
      inhibitory potency<100 microM, and four of them exhibited IC50 values<10 microM.
      One compound, 62, with an IC50 value of 0.6 microM, displayed better potency than
      the original chalcone 2 against the strand transfer process. This study
      demonstrates the systematic use of pharmacophore technologies to discover novel
      structurally diverse inhibitors based on lead molecules that would exhibit poor
      characteristics in vivo. The identified compounds have the potential to exhibit
      favorable pharmacokinetic and pharmacodynamic profiles.

PMID- 17502149
TI  - Modulating paclitaxel bioavailability for targeting prostate cancer.
AB  - Four novel water-soluble peptide-paclitaxel conjugates were designed and
      synthesized as prostate-specific antigen (PSA)-activated prodrugs for prostate
      cancer therapy. These prodrugs were composed of a peptide, HSSKLQ or SSKYQ, each
      of which is selectively cleavable by PSA; a self-immolative linker, either para
      aminobenzyl alcohol (PABS) or ethylene diamine (EDA); and the parent drug,
      paclitaxel. Introduction of a PABA or EDA linker between the peptide and
      paclitaxel in prodrugs 2-5 resulted in products with an increased rate of
      hydrolysis by PSA. The stability of prodrugs 2 and 3, with the PABA linker, was
      poor in the serum-containing medium because of the weak carbonate bond between
      the PABA and paclitaxel; however, this disadvantage was overcome by introducing a
      carbamate bond using an EDA linker in prodrugs 4 and 5. Thus, the incorporation
      of an EDA linker increased both the stability and PSA-mediated activation of
      these prodrugs. The cytotoxicity of each prodrug, as compared to paclitaxel, was
      determined against a variety of cell lines, including the PSA-secreting CWR22Rv1
      prostate cancer cell line. The EDA-derived prodrug of paclitaxel 5 was stable and
      capable of being efficiently converted to an active drug that killed cells
      specifically in the presence of PSA, suggesting that this prodrug and similarly
      designed PSA-cleavable prodrugs may have potential as prostate cancer-specific
      therapeutic agents.

PMID- 17502151
TI  - Membrane effects of 2,4-dichlorophenoxyacetic acid in motor cells of Mimosa
      pudica L.
AB  - 2,4-dichlorophenoxyacetic acid applied to excised leaves of Mimosa pudica L.
      inhibited in a dose-dependent manner the shock-induced pulvinar movement. This
      inhibition was negatively correlated with the amount of [(14)C] 2,4
      dichlorophenoxyacetic acid present in the vicinity of the motor cells. Although
      2,4-dichlorophenoxyacetic acid is a weak acid, its greatest physiological
      efficiency was obtained with pH values close to neutrality. This observation
      opens the question of its mode of action which may be through external signaling
      or following internal transport by a specific anionic form transporter. The
      effect was related to molecular structure since 2,4-dichlorophenoxyacetic
      acid>3,4-dichlorophenoxyacetic acid>2,3-dichlorophenoxyacetic acid. An essential
      target of 2,4-dichlorophenoxyacetic acid action lies at the plasmalemma as
      indicated by the induced hyperpolarization of the cell membrane. Compared to
      indole-3-acetic acid and fusicoccin, it induced a complex effect on H(+) fluxes.
      Applied to plasma membrane vesicles purified from motor organs, 2,4
      dichlorophenoxyacetic acid enhanced proton pumping, but, unlike fusicoccin, it
      did not increase the H(+)-ATPase catalytic activity in our experimental
      conditions. Taken together, the data suggest that 2,4-dichlorophenoxyacetic acid
      acts on cell turgor variation and the concomittant ion migration, in particular
      K(+), by a mechanism involving specific steps compared to indole-3-acetic acid
      and fusicoccin.

PMID- 17502150
TI  - New, stronger nucleophiles for nucleic acid-templated chemistry: Synthesis and
      application in fluorescence detection of cellular RNA.
AB  - Nucleic acid-templated chemistry is a promising strategy for imaging genetic
      sequences in living cells. Here we describe the synthesis of two new nucleophiles
      for use in templated nucleophilic displacements with DNA probes. The nucleophilic
      groups are phosphorodithioate and phosphorotrithioate; we report on synthetic
      methods for introducing these groups at the 3'-terminus of oligonucleotides. Both
      new nucleophiles are found to be more highly reactive than earlier
      phosphoromonothioates. This increased nucleophilicity is shown to result in more
      rapid templated reactions with electrophilic DNA probes. The new probes were
      demonstrated in detection of specific genetic sequences in solution, with clear
      signal over background being generated in as little as 20 min. The probes were
      also tested for imaging ribosomal RNA sequences in live Escherichia coli; useful
      signal was generated in 20 min to 1h, approximately one quarter to one-half the
      time of earlier monothioate probes, and the signal-to-noise ratio was increased
      as well.

PMID- 17502152
TI  - Controlled atmosphere treatment of broccoli after harvest delays senescence and
      induces the expression of novel BoCAR genes.
AB  - The current study examines the transcription of four genes (BoCAR1A, BoCAR5,
      BoCAR6-4 and BoCAR25) found to be up-regulated in response to high CO(2)/low O(2)
      treatment in broccoli (Brassica oleracea). Messenger RNA levels for the four
      genes declined after tissues were removed from CA. Physiological and biochemical
      changes and gene expression patterns were examined in broccoli tissues held in
      one of four different atmospheres, namely air (<1% CO(2), 21% O(2)), high carbon
      dioxide and low oxygen (CA 10% CO(2), 5% O(2)), low oxygen (0% CO(2), 5% O(2)),
      and high carbon dioxide (10% CO(2), 20% O(2)). In a second trial gene expression
      was examined in tissues held for short periods in CA (6h, 12h or 24h) followed by
      air. Broccoli tissues were also exposed to CA after 48 h in air to determine
      whether CA treatment was effective in up-regulating the CA-responsive genes
      and/or delaying senescence after early senescence-associated gene changes had
      been initiated. Northern analysis showed that a combined high CO(2) and low O(2)
      atmosphere was more effective than high CO(2) or low O(2) alone for inducing
      maximum gene expression and delaying postharvest broccoli senescence. In
      addition, broccoli tissues responded to CA treatment after a 48-h period in air
      with increased CA-responsive gene expression. Certain transcripts were down
      regulated in tissues exposed to salt and water stresses that promoted senescence,
      and down-regulated in tissues treated with cytokinin, a treatment that delays
      postharvest senescence in broccoli. The up-regulation of these four BoCAR genes
      appears to be specific to CA treatment in harvested broccoli tissues.

PMID- 17502153
TI  - Composition, speciation and distribution of iron minerals in Imperata cylindrica.
AB  - A comparative study of the roots, rhizomes and leaves of an iron hyperaccumulator
      plant, Imperata cylindrica, isolated from the banks of an extreme acidic
      environment, using complementary techniques: Mosbauer spectroscopy (MS), X-ray
      diffraction (XRD), scanning electron microscopy (SEM) coupled to energy
      dispersive X-ray microanalysis (EDAX) and transmission electron microscopy (TEM),
      has shown that two main biominerals, jarosite and ferrihydrate-ferritin,
      accumulate in the different tissues. Jarosite accumulates mainly in roots and
      rhizomes, while ferritin has been detected in all the structures. A model of iron
      management in I. cylindrica is presented.

PMID- 17502155
TI  - Establishment of immortalized rat Kupffer cell lines.
AB  - BACKGROUND: Kupffer cells have been implicated in the pathogenesis of various
      liver diseases. Primary cultures of Kupffer cells have a very limited life span,
      tend to de-differentiate and become senescent, and therefore are not suitable for
      cell signaling studies. AIM: To establish immortalized rat Kupffer cell lines
      that facilitate mechanistic studies of cell signaling and signal transduction.
      METHODS: Rat Kupffer cells were sub-cultured with EGF to obtain rat Kupffer Cell
      line 1 (RKC1), and subsequently transfected with Simian Virus 40 Large T-antigen
      expression vector to obtain rat Kupffer Cell line 2 (RKC2). RESULTS: RKC1 and
      RKC2 are similar to primary Kupffer cells as they express the molecular markers
      ED1, ED2, ED3, and F4/80, and upregulate TNF-alpha, IL-6, IL-1beta, Fas /FasL,
      and NF-kappaB, as well as TLR4 in response to LPS or pancreatic elastase.
      Additionally, RKC1 and RKC2 maintain phagocytic properties of latex beads and
      exhibit increased telomerase and stabilized p53 activity. CONCLUSION:
      Immortalized RKC1 and RKC2 cells maintain properties of primary Kupffer cells and
      can be valuable tools in evaluating the role of Kupffer cells in immune diseases
      and in liver-cell based drug discovery.

PMID- 17502156
TI  - Detection of supercoiled plasmid DNA and luciferase expression in Atlantic salmon
      (Salmo salar L.) 535 days after injection.
AB  - In this study our aim was to investigate the persistence and distribution of
      plasmid DNA in Atlantic salmon. Atlantic salmon (mean weight 70 g) were injected
      with 100 microg of plasmid DNA in 100 microl of phosphate buffered saline. The
      fish were reared in running fresh water at temperature 0-12 degrees C and
      injections were performed at 8 degrees C. After intramuscular injection, samples
      were obtained from blood and different tissues and organs up to day 535 after
      injection. We found by use of Southern blotting open circular and supercoiled
      plasmid DNA at the injection site and plasmid DNA fragments, assessed by real
      time PCR, were detected in some of the examined tissues up to day 535. A co
      persistence of luciferase transcript and activity were identified at the
      injection site up to day 535, however analysis of DAM methylation pattern
      suggested that the plasmid DNA did not replicate in vivo. Our study indicated
      that the plasmid DNA can persist for a prolonged time after intramuscular
      injection.

PMID- 17502158
TI  - Patella malalignment, pain and patellofemoral progression: the Health ABC Study.
AB  - OBJECTIVE: Patellofemoral (PF) joint osteoarthritis (OA) is strongly correlated
      with lower extremity disability and knee pain. Risk factors for pain and
      structural progression in PF OA are poorly understood. Our objective was to
      determine the association between patella malalignment and its relation to pain
      severity, and PF OA disease progression. METHODS: We conducted an analysis of
      data from the Health ABC knee OA study. Health ABC is a community based, multi
      center cohort study of 3075 Caucasian and Black men and women aged 70-79 at
      enrollment. Weight bearing skyline knee X-rays were obtained in a subset (595) of
      subjects, with and without knee pain, at year 2 and year 5 (mean follow-up 36
      months). Films were read paired, and PF osteophytes (OST) and joint space
      narrowing (JSN) were scored on a 0-3 scale using the Osteoarthritis Research
      Society International atlas. We defined progression of PF OA as any increase in
      JSN score. Three measures of patella malalignment were made: sulcus angle;
      patella tilt angle; and patella subluxation medially or laterally (bisect
      offset). Knee symptoms were assessed using a knee specific Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) knee pain subscale. We
      assessed the relationship between baseline patella malalignment and pain severity
      (linear regression for WOMAC) and compartment specific PF OA progression
      (logistic regression for dichotomous outcomes). We classified continuous measures
      of patella alignment into quartile groups. We performed multivariable adjusted
      logistic regression models, including age, gender and body mass index (BMI) to
      assess the relation of baseline patella alignment to the occurrence of PF JSN
      progression using generalized estimating equations (GEE). RESULTS: The subjects
      had a mean age 73.6 (SD 2.9), BMI 28.8 (SD 4.9), 40.3% male, and 46% were Black.
      Medial displacement of the patella predisposed to medial JSN progression; odds
      for each quartile 1, 1.2, 1.2, 2.2 (P for trend=0.03), whilst protecting from
      lateral JSN progression; odds for each quartile 1, 0.7, 0.6, 0.4 (P for
      trend=0.0004). Increasing patella tilt protected from medial JSN progression;
      odds for each quartile 1, 0.8, 0.5, 0.2 (P<0.0001) and trended to increasing pain
      severity (P=0.09). CONCLUSION: Patella malalignment is associated with PF disease
      progression. Medial displacement and tilt of the patella predisposes to medial
      JSN progression, whilst lateral displacement is predictive of lateral JSN
      progression. The influence of patella malalignment has important implications
      since it is potentially modifiable through footwear, taping and/or knee bracing.

PMID- 17502159
TI  - Chondrogenic potential of human synovial mesenchymal stem cells in alginate.
AB  - OBJECTIVE: In a recent study, we demonstrated that mesenchymal stem cells (MSCs)
      derived from the synovial membranes of bovine shoulder joints could differentiate
      into chondrocytes when cultured in alginate. The purpose of the present study was
      to establish the conditions under which synovial MSCs derived from aging human
      donors can be induced to undergo chondrogenic differentiation using the same
      alginate system. METHODS: MSCs were obtained by digesting the knee-joint synovial
      membranes of osteoarthritic human donors (aged 59-76 years), and expanded in
      monolayer cultures. The cells were then seeded at a numerical density of
      4x10(6)/ml within discs of 2% alginate, which were cultured in serum-containing
      or serum-free medium (the latter being supplemented with 1% insulin, transferrin,
      selenium (ITS). The chondrogenic differentiation capacity of the cells was tested
      by exposing them to the morphogens transforming growth factor-beta1 (TGF-beta1),
      TGF-beta2, TGF-beta3, insulin-like growth factor-1 (IGF-1), bone morphogenetic
      protein-2 (BMP-2) and BMP-7, as well as to the synthetic glucocorticoid
      dexamethasone. The relative mRNA levels of collagen types I and II, of aggrecan
      and of Sox9 were determined quantitatively by the real-time polymerase chain
      reaction (PCR). The extracellular deposition of proteoglycans was evaluated
      histologically after staining with Toluidine Blue, and that of type-II collagen
      by immunohistochemistry. RESULTS: BMP-2 induced the chondrogenic differentiation
      of human synovial MSCs in a dose-dependent manner. The response elicited by BMP-7
      was comparable. Both of these agents were more potent than TGF-beta1. A higher
      level of BMP-2-induced chondrogenic differentiation was achieved in the absence
      than in the presence of serum. In the presence of dexamethasone, the BMP-2
      induced expression of mRNAs for aggrecan and type-II collagen was suppressed; the
      weaker TGF-beta1-induced expression of these chondrogenic markers was not
      obviously affected. CONCLUSIONS: We have demonstrated that synovial MSCs derived
      from the knee joints of aging human donors possess chondrogenic potential. Under
      serum-free culturing conditions and in the absence of dexamethasone, BMP-2 and
      BMP-7 were the most potent inducers of this transformation process.

PMID- 17502157
TI  - A comprehensive molecular phylogeny of the starlings (Aves: Sturnidae) and
      mockingbirds (Aves: Mimidae): congruent mtDNA and nuclear trees for a
      cosmopolitan avian radiation.
AB  - We generated a comprehensive phylogeny for the avian families Sturnidae
      (starlings, mynas, Rhabdornis, oxpeckers, and allies) and Mimidae (mockingbirds,
      thrashers, and allies) to explore patterns of morphological and behavioral
      diversification. Reconstructions were based on mitochondrial DNA sequences from
      five coding genes (4108 bp), and nuclear intron sequences from four loci (2974
      bp), for most taxa, supplemented with NDII gene sequences (1041 bp) derived from
      museum skin specimens from additional taxa; together the 117 sampled taxa
      comprise 78% of the 151 species in these families and include representatives of
      all currently or recently recognized genera. Phylogenetic analyses consistently
      identified nine major clades. The basal lineage is comprised of the two Buphagus
      oxpeckers, which are presently confined to Africa where they are obligately
      associated with large mammals. Some species in nearly all of the other major
      clades also feed on or around large vertebrates, and this association may be an
      ancestral trait that fostered the world-wide dispersal of this group. The
      remaining taxa divide into sister clades representing the New-World Mimidae and
      Old-World Sturnidae. The Mimidae are divided into two subclades, a group of
      Central American and West Indian catbirds and thrashers, and a pan-American clade
      of mockingbirds and thrashers. The Sturnidae are subdivided into six clades. The
      Phillipine endemic Rhabdornis are the sister lineage to a larger and
      substantially more recent radiation of South Asian and Pacific island starlings
      and mynas. A clade of largely migratory or nomadic Eurasian starlings (within
      which the basal lineage is the model taxon Sturnus vulgaris) is allied to three
      groups of largely African species. These reconstructions confirm that Buphagus
      should not be included in the Sturnidae, and identify many genera that are not
      monophyletic. They also highlight the substantial diversity among the major
      Sturnidae subclades in rates of species accumulation, morphological
      differentiation, and behavioral variation.

PMID- 17502160
TI  - Quantitative MRI of parallel changes of articular cartilage and underlying
      trabecular bone in degeneration.
AB  - OBJECTIVE: To determine the interrelations between degenerative changes in
      articular cartilage and underlying trabecular bone during development of
      osteoarthritis and to test the ability of quantitative magnetic resonance imaging
      (MRI) to detect those changes. METHODS: Human cadaver patellae were investigated
      with quantitative MRI methods, T(2) and dGEMRIC, at 1.5T. Same measurements for
      isolated cartilage samples were performed at 9.4T. Bone samples, taken at sites
      matched with cartilage analyses, were measured with MRI and peripheral
      quantitative computed tomography (pQCT). Mechanical and quantitative microscopic
      methods were also utilized for both cartilage and bone samples. RESULTS:
      Significant differences were found between the samples with different stages of
      degeneration in mechanical properties, T(2) at 1.5T and proteoglycan (PG) content
      of articular cartilage. dGEMRIC at 9.4T discerned samples with advanced
      degeneration from the others. Bone variables measured with pQCT discerned samples
      with no or minimal and advanced degeneration, and mechanical properties of
      trabecular bone discerned samples with no or minimal degeneration from the
      others. Significant linear correlations were found between the bone and cartilage
      parameters. Characteristically, associations between variables were stronger
      within the samples with no or minimal degeneration compared to all samples.
      CONCLUSIONS: Quantitative MRI variables, especially T(2) relaxation time of
      articular cartilage, may be feasible surrogate markers for early and advanced
      osteoarthritic changes in joint tissues, including decreased elastic moduli, PG
      and collagen contents of cartilage and mineral density and volume fraction of
      trabecular bone. Further work is required to resolve the relaxation mechanisms at
      clinically applicable field strengths.

PMID- 17502161
TI  - Brachyspina syndrome in two Holstein calves.
AB  - Brachyspina syndrome, a rare lethal skeletal malformation, is described in two
      Italian Holstein calves. Both calves were stillborn and had shortened trunks with
      long legs. Radiography demonstrated several abnormalities of the cervical and
      thoracolumbar vertebral column. Visceral malformations involving the heart,
      kidney, genital tract and gastrointestinal system were also found. Both calves
      were traced back to the same sire and an inherited basis was strongly suspected.

PMID- 17502162
TI  - Mutations in the phenylalanine hydroxylase gene identified in 95 patients with
      phenylketonuria using novel systems of mutation scanning and specific genotyping
      based upon thermal melt profiles.
AB  - Phenylketonuria (PKU, MIM 261600; EC 1.14.16.1) results from mutations in the
      phenylalanine hydroxylase (PAH) gene. Newborn metabolic disease screening uses
      blood dried on filter paper (DBS) to prospectively identify candidate newborns
      affected with PKU via an elevated concentration of phenylalanine. However, it is
      then important to confirm the specific category of PKU since classical PKU
      requires a stringent diet while milder categories may not require diet and a very
      important BH4-responsive category may be treated with the PAH cofactor 6R
      tetrahydrobiopterin (BH4). Since there is a close genotype-phenotype correlation
      in PKU, determining the PAH genotype can be extremely important for therapy as
      well as prognosis. A simple and rapid method of accurately determining the PAH
      genotype would be a valuable addition to the diagnosis of PKU. Described herein
      is a means to identify variants in the PAH gene using high-resolution melt
      profiling, which compares the thermal denaturation profile of a patient sample to
      that of a control. Regions where the patient and control samples produce a common
      profile were not further evaluated, while those regions where the patient profile
      deviates from the control were assessed by DNA sequencing. Additionally described
      is a scheme utilizing redundant analysis with melt profile controls and a novel
      multiplex genotyping assay to triage deviation owing to known polymorphisms. Two
      mutations were identified in 93 of the 95 patients assessed and in the remaining
      two patients a single mutation was identified. Melt profiling provided 99%
      sensitivity to identify sequence variants in the PAH gene.

PMID- 17502165
TI  - Coherence in children with Attention-Deficit/Hyperactivity Disorder and excess
      beta activity in their EEG.
AB  - OBJECTIVE: This study investigated differences in coherence measures between two
      groups of children with Attention-Deficit/Hyperactivity Disorder (ADHD) - with
      the typical EEG profile (increased theta and decreased beta activity), and with
      excess beta activity - and a normal control group. METHODS: Thirty-four children
      with ADHD were included in each of the typical and excess beta groups, and were
      age and sex matched with 34 control subjects. EEG was recorded from 21 sites
      during an eyes-closed resting condition. Wave-shape coherence was calculated for
      eight intrahemispheric and eight interhemispheric electrode pairs, for the delta,
      theta, alpha and beta bands. RESULTS: In comparison to the controls, the typical
      ADHD group primarily had increased intrahemispheric theta and beta coherence at
      short-medium inter-electrode distances, and increased interhemispheric coherence
      for theta in the frontal and central/parietal/occipital regions. Their laterality
      effect for interhemispheric short-medium inter-electrode distances was reduced in
      the theta band. Differences between the excess beta group and the control group
      were primarily found in laterality of the intrahemispheric theta coherence at
      short-medium electrode distances, and increased interhemispheric theta coherence
      in the frontal regions. Reduced delta coherence in the temporal regions was also
      found. CONCLUSIONS: These results suggest that ADHD children with excess beta
      power have an underlying brain dysfunction in the frontal lobes which is found in
      common with children with the typical EEG profile. However a number of
      qualitative differences exist which could be associated with other aspects of the
      ADHD diagnosis or another comorbid condition. SIGNIFICANCE: This is the first
      study to investigate EEG coherence in ADHD children who have increased beta
      power.

PMID- 17502163
TI  - On and Off magnetic auditory evoked responses in early infancy: a possible marker
      of brain immaturity.
AB  - OBJECTIVE: To follow the development of the auditory evoked on- and off-responses
      in early infancy. METHODS: The subjects were healthy infants, studied at
      conceptional age (CA) 39-66 weeks. Serial auditory evoked responses (AERs) were
      recorded in 17 subjects in response to tones of frequency 1.5 kHz and duration
      1.0 s in order to follow the development of the AERs. Two small substudies were
      performed to examine off-responses evoked by tones of varying duration. The first
      used 0.2, 0.3, 0.4, and 0.5s tones; the second used 0.5, 1.0, and 2.0 s tones.
      RESULTS: For the 1.0 s tones, the on- and off-responses consisted of three
      components: P250, P400, and N750 m. The on- and off-responses had similar
      amplitude, in contrast to adult AERs in which the on-responses are typically much
      larger. Prior to about CA 47 weeks, the on-responses were actually smaller on
      average than the off-responses, and in infants born prior to CA 38 weeks the AERs
      were dominated by the off-response. Off-responses were seen for tones as brief as
      0.2 s; however, the P400m component was often absent in the off-responses for
      tone durations < or = 0.5 s. An interaction was observed in which the N750 m-On
      component was strongly suppressed when it overlapped the P250 m-Off. CONCLUSIONS:
      Off-responses are much more prominent in infant than in adult AERs, especially in
      pre-term infants and at early CAs. On- and off-responses also exhibit more
      complex behavior in infants than in adult; the individual components can interact
      and behave independently. SIGNIFICANCE: Measurement of auditory off-responses can
      improve the assessment of infant neurodevelopment, potentially providing a marker
      of brain immaturity.

PMID- 17502166
TI  - Further evidence for NMDA-dependence of the after-effects of human theta burst
      stimulation.

PMID- 17502167
TI  - Aligning two RNA secondary structures with l-block.
AB  - RNA sequences can form structures which are conserved throughout evolution and
      the question of aligning two RNA secondary structures has been extensively
      studied. Most of the previous alignment algorithms require the input of gap
      opening and gap extension penalty parameters. The choice of appropriate parameter
      values is controversial as there is little biological information to guide their
      assignment. In this paper, we present an algorithm which circumvents this
      problem. Instead of finding an optimal alignment with predefined gap opening
      penalty, the algorithm finds the optimal alignment with exact number of aligned
      blocks.

PMID- 17502168
TI  - Backyard burning.
AB  - This study was undertaken to determine whether changes had occurred in the
      numbers of burns that could be related to backyard burning subsequent to the
      introduction of the council tax throughout Eire for the collection of household
      refuse. Numbers of patients admitted to our unit who had sustained burns by
      burning rubbish were recorded prospectively over a period of 12 months. A random
      control group was taken as three years prior to this and results found by
      retrospective chart review. Between January and November 2005, 168 patients were
      admitted to the National Burns Unit, St James's Hospital Dublin, Ireland.
      Nineteen of these patients sustained flame burns from backyard burning. One
      hundred and seventy patients were admitted in the comparative period of 2002;
      Seven of these from backyard burning. The total number of inpatient days for
      these patients in 2005 (255) was significantly more than in 2002 (68) (p=0.024).
      The numbers in our study show a marked increase in the number of patients
      sustaining burns in this manner, and appear to correlate with the introduction of
      bin charges by a number of county councils around the country last year. This
      study demonstrates that the introduction of legislation can have an unforeseen
      adverse affect on the population if not introduced in correlation with
      appropriate public education. While the introduction of waste charges represents
      a very necessary move forward in waste disposal in Ireland, public awareness
      campaigns should be implemented to prevent further such injuries from occurring.

PMID- 17502169
TI  - Bronchioloalveolar carcinoma arising in a congenital pulmonary airway
      malformation in a child: case report with an update of this association.
AB  - An 8-year-old girl was evaluated for a mass in the left pulmonary lobe. Her
      clinical history was remarkable for an intermittent dry cough since the age of 2,
      with recurrent episodes of purulent sputum and fever. She underwent left lower
      lobectomy, which was found to be a bronchioloalveolar carcinoma arising in a type
      1 congenital pulmonary airway malformation at pathologic examination. No
      additional therapies were undertaken. Two years after resection, imaging studies
      showed 5 contralateral pulmonary nodules suggestive of disseminated disease with
      a poor outcome. A review of presentation, treatment, and outcome of this
      association was made.

PMID- 17502170
TI  - Successful laparoscopic ligation of the lymphatic trunk for refractory chylous
      ascites.
AB  - A 3-year-old girl with recurrent chylous ascites was successfully treated by
      laparoscopic ligation of the ruptured lymphatic trunk. She was referred to our
      hospital at 16 days of age because of marked abdominal distension. Imaging
      methods showed massive ascites of unknown origin, and analysis of the ascites
      revealed its chylous nature. Conservative treatments were started. Her condition
      improved to some extent, and she was discharged. Two years later, she was
      readmitted with abdominal distension and loss of appetite. Laparoscopic surgery
      was planned to clarify the etiology and to treat intractable ascites. Sudan black
      B was orally administered, and laparoscopy revealed the presence of a whitish
      gray fluid in the abdominal cavity, and a dark-blue stream of the dye was
      noticed. The responsible lesion of the chylous ascites was detected by tracking
      the stream. The lesion was ligated twice with an endoloop. She has been
      completely free from the symptoms for 3 years and 9 months. This experience
      indicates the usefulness of laparoscopic surgery in investigating the etiology of
      chylous ascites and treating it. The concomitant use of a lipophilic dye is
      mandatory to find the responsible lesion at surgery. Laparoscopic surgery,
      instead of open surgery, should be considered as a treatment of choice for
      intractable chylous ascites.

PMID- 17502171
TI  - Obstructing ileal duplication cyst infected with Salmonella in a 2-year-old boy:
      a case report and review of the literature.
AB  - Alimentary tract duplications (ATDs) are rare congenital anomalies, with an
      incidence of 1 in 4500 individuals. Patients with these lesions present in a
      variety of ways, and although histologically benign, ATDs can lead to lethal
      complications including volvulus, intussusception, or bowel obstruction.
      Irrespective of anatomical location, the epithelial lining of ATDs contains
      ectopic acid-secreting mucosa in more than 50% of cases, which can lead to
      ulceration, bleeding, or transmural erosion and perforation. We report an unusual
      case of a child who presented with small bowel obstruction caused by an ileal
      duplication cyst that had become infected with Salmonella. Although reports of
      infected mesenteric cysts and duodenal duplication cysts have been published,
      this is the first reported case of an infected ileal duplication cyst. We also
      present a review of the literature regarding these interesting lesions.

PMID- 17502172
TI  - Laparoscopic splenopexy and cystectomy for an enlarged wandering spleen and
      splenic cyst.
AB  - Wandering spleen is an uncommon condition, which can present emergently in
      children. Similarly, nonparasitic splenic cysts are also rarely encountered. In
      this report, we describe a massive wandering spleen (22 cm in longitudinal
      dimension) with a pseudocyst (4.6 x 2 cm) in the inferior pole in an asymptomatic
      16-year-old adolescent. Only 4 similar cases have been reported in the
      literature; 2 of them have been in the pediatric age group. These 2 conditions
      were diagnosed while she was being evaluated for dysmenorrhea, and she was
      referred for surgical consultation. The cyst was excised laparoscopically, and
      the spleen was placed into an extraperitoneal pouch. To date, there are no other
      reports describing laparoscopic cystectomy and splenopexy in a teenager.

PMID- 17502173
TI  - Left congenital diaphragmatic hernia, absent pericardium, and liver heterotopia:
      a case report and review.
AB  - A case of a left congenital diaphragmatic hernia (CDH), absent pericardium, and a
      hernial sac containing ectopic liver tissue is presented. This triplicate of
      defects is exceedingly rare with only 2 previous reports in the literature dating
      back to 1936. This case supports the evidence that CDH is the result of failure
      of the closure of the pleuroperitoneal canals by the growth of the posthepatic
      mesenchymal plate. Moreover, the role of the phrenic nerve as a mediator for both
      CDH and absent pericardium is discussed.

PMID- 17502174
TI  - Retroperitoneal displacement of ovary and fallopian tube: a complication of
      surgical management of incarcerated inguinal hernia in female infants.
AB  - Sliding indirect inguinal hernias containing the ipsilateral uterine adnexa are
      not uncommon in female infants. We report a case of a 12-year-old girl presenting
      with a benign tumor (serous cystadenofibroma) in a retroperitoneally located
      ovary. The patient had a history of hernia repair in the neonatal period.
      Displacement of the ovary and fallopian tube in the retroperitoneal space is a
      rarely reported complication of pediatric inguinal hernia surgery. Uncorrected,
      this can result in hormonal dysfunction, decreased fertility, and difficult and
      unclear situations during abdominal surgery in adulthood. A laparoscopic approach
      for hernia repair may prevent this complication.

PMID- 17502175
TI  - Neurenteric cyst--a case report of this rare disorder.
AB  - Neurenteric cysts are rare congenital lesions that are believed to be the result
      of the split notochord syndrome. We report the clinical case of a 5-year-old boy
      presenting with vague gastrointestinal symptoms and fatigue, who had undergone
      resection of a small intestine duplication cyst as a newborn. Computed tomography
      revealed a mediastinal neurenteric cyst with partial destruction of several
      thoracic vertebrae. Resection of the tumor proved effective. Recognition of this
      disorder is important: because of its benign nature, the prognosis after surgical
      resection can be good. If the diagnosis is made in an early stage, unnecessary
      progressive destruction of surrounding structures may be prevented.

PMID- 17502176
TI  - Preoperative evaluation of the trachea in a child with pulmonary artery sling
      using 3-dimensional computed tomographic imaging and virtual bronchoscopy.
AB  - Pulmonary artery sling is frequently accompanied by tracheal anomalies other than
      local compression, including focal/segmental or extensive stenosis (ring-sling
      complex). Recent advances in computed tomography technology, such as
      multidetector computed tomography with 3-dimensional imaging (3-D) and virtual
      bronchoscopy (VB), offer important and accurate information of the entire
      tracheobronchial tree. We report on the value of 3-D imaging and VB in the
      preoperative assessment of a 4-year-old child with pulmonary artery sling and
      long segment tracheal stenosis owing to complete cartilaginous rings; we suggest
      that 3-D imaging and VB are important contributions in this assessment.

PMID- 17502178
TI  - Intravenous vasoactive intestinal polypeptide lowers pulmonary-to-systemic
      vascular resistance ratio in a neonatal piglet model of pulmonary arterial
      hypertension.
AB  - BACKGROUND: Several studies of vasoactive intestinal polypeptide (VIP)
      demonstrated its potent vasodilative effects on pulmonary and systemic
      circulation. However, no hemodynamic studies were performed to depict the effects
      of VIP in an in vivo model of pulmonary arterial hypertension (PAH), thereby
      limiting a complete understanding of the overall hemodynamic effects of VIP in
      PAH. METHODS AND RESULTS: The pulmonary and systemic hemodynamic effects of
      intravenous infusion of 100 ng/kg per minute of VIP in control and pulmonary
      hypertensive piglets at 6 to 8 weeks of age were assessed. Pulmonary arterial
      hypertension was induced after the instillation of meconium solution in the
      subjects' trachea and was characterized by the establishment of a persistently
      elevated pulmonary arterial pressure, diminished cardiac output, and elevated
      pulmonary-to-systemic vascular resistance (PVR/SVR) ratio. CONCLUSIONS:
      Continuous intravenous infusion of VIP markedly decreased PVR/SVR ratio in
      pulmonary hypertensive subjects; however, it lowered blood pressure without
      causing any significant changes in PVR/SVR ratio in control subjects.
      Collectively, these results suggest an overall pulmonary vasodilative effect of
      VIP in PAH.

PMID- 17502179
TI  - Emergence of community-acquired methicillin-resistant Staphylococcus aureus soft
      tissue infections.
AB  - PURPOSE: Our objective is to describe the changing incidence of community
      acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and its treatment
      within East Tennessee. METHODS: A retrospective chart review of 245 patients
      treated with incision and drainage of soft tissue infections from March 2000 to
      September 2005 was completed. Consent was obtained from our local institutional
      review board. Forty patients were excluded because no cultures were recorded or
      because they failed the criteria for the diagnosis of CA-MRSA. We examined our
      data using chi2 analysis. P value of less than .05 was considered statistically
      significant. RESULTS: The most common organism cultured was CA-MRSA (33%; 67 of
      205). Non-CA-MRSA accounted for 4% (9 of 205). The age of patients ranged from 1
      month to 21 years, with a mean age of 6.5 years. Stratified by year, the
      incidence of positive cultures for CA-MRSA has increased 159% since 2004 and 868%
      since 2003. In addition, the average age of patients has decreased from 8.3 years
      in 2000 to 6.1 years in 2005. CONCLUSIONS: Community-acquired MRSA has emerged as
      the dominant source of soft tissue infection requiring incision and drainage
      regardless of site in East Tennessee. This has caused a change in the choice of
      empiric antibiotic treatment of soft tissue abscesses in our region. These
      infections now account for the third most common reportable disease to the
      Department of Health in East Tennessee.

PMID- 17502180
TI  - MCRA of an anastomotic stenosis after esophagoesophagostomy for long gap
      esophageal atresia: a case report.
AB  - A 25-month-old boy with long gap esophageal atresia developed severe esophageal
      stenosis refractory to balloon dilatations after definitive
      esophagoesophagostomy. At 33 months of age, the patient had a magnetic
      compression revision anastomosis, in which a pair of 2 cylindrical Samarium
      cobalt rare-earth 320 mT (3200 G) magnets, 15 x 5 mm (diameter x thickness), were
      placed in the esophagus to compress the scar tissue of the anastomosis. The
      magnets were retrieved 34 days after the magnetic compression revision
      anastomosis procedure. For 3 months, the patient subsequently had balloon
      dilatations to prevent restenosis, and he has been able to eat normally by mouth
      without further balloon dilatations since then.

PMID- 17502181
TI  - Inflammatory markers for acute appendicitis in children: are they helpful?
AB  - BACKGROUND/PURPOSE: Diagnosis of acute appendicitis in children remains
      challenging, and the role of blood tests in the decision-making process is still
      unclear. We prospectively evaluated if routine inflammatory markers could
      contribute to exclude the presence of acute appendicitis in children. METHODS:
      Preoperative white blood cell count (WBCC) and C-reactive protein (CRP) were
      prospectively tested in children undergoing surgery for suspected appendicitis.
      Surgery was indicated on the basis of clinical findings and/or ultrasound scan,
      but WBCC and CRP values were ignored during the decision-making process.
      Sensitivity of individual markers and their combinations were assessed. RESULTS:
      One hundred children (55 males) with a mean age of 9.34 years (SD, 3.54 years)
      had pathologically confirmed diagnosis of appendicitis. A perforated appendix was
      found in 23% of cases. Elevated WBCC alone had a sensitivity of 0.6 (confidence
      interval [CI], 0.506-0.694). Sensitivity of elevated CRP alone was 0.86 (CI,
      0.926-0.793). Elevation of either WBCC or CRP or both had a sensitivity of 0.98
      (CI, 1.0-0.953). CONCLUSIONS: White blood cell count or CRP values alone do not
      appear to provide any useful additional information to the surgeon. However, the
      sensitivity of the 2 combined tests is extremely high, and normal values of both
      WBCC and CRP are very unlikely in pathologically confirmed appendicitis.

PMID- 17502182
TI  - Amnioexchange for fetuses with gastroschisis: is it effective?
AB  - BACKGROUND/PURPOSE: Amniotic fluid of fetuses with gastroschisis (GS) contains
      inflammatory mediators, gastrointestinal, and urinary waste products. Dilution
      and removal of such harmful substances have been advocated to prevent damage to
      the herniated intestine. We evaluated the effectiveness of serial amnioexchange
      procedures in 8 consecutive fetuses with GS. METHODS: Amnioexchange was performed
      bimonthly during the third trimester. Amniotic fluid collected before each
      procedure was tested for pH, osmolarity, urea, creatinine, cystatin-C, proteins,
      albumin, bilirubin, biliary salts, pancreatic amylase, serum amyloid A, C
      reactive protein, alanine transaminase (ALT), alcaline phosphatase (ALP), gamma
      glutamyl transpetidase (gammaGT), tumor necrosis factor alpha, interleukin 2,
      interleukin 6, epidermal growth factor, transforming growth factor beta, and
      myeloperoxidase. RESULTS: A total of 25 samples (median, 3 per fetus) were
      examined. Biochemical or inflammatory markers did not correlate with gestational
      age, nor was any trend observed in values from individual patients during the
      course of amnioexchange treatment. There was no correlation between biochemical
      or inflammatory markers and clinical outcome, including time to full enteral
      feeding. CONCLUSIONS: Serial amnioexchanges did not modify the biochemical or
      inflammatory status of amniotic fluid nor appeared to prevent injury to the
      herniated gut. Because repeated amnioexchanges may carry some risks, their use in
      fetuses with GS is not recommended outside the setting of a prospective
      randomized trial.

PMID- 17502183
TI  - Effects of intrauterine treatment on interstitial cells of Cajal in
      gastroschisis.
AB  - AIM: An experimental study was performed to investigate the effects of amnio
      allantoic fluid exchange and intrauterine bicarbonate treatment on intestinal
      damage and interstitial cells of Cajal (ICC) in gastroschisis. MATERIALS AND
      METHODS: Thirteen-day-old fertilized chick eggs were randomly allocated into 4
      groups as control, gastroschisis, gastroschisis + amnio-allantoic fluid exchange,
      and gastroschisis + bicarbonate treatment groups. In the treatment groups, amnio
      allantoic exchange and bicarbonate treatments were performed for 3 days, after
      creating gastroschisis. Specimens were processed for hematoxylin-eosin and c-kit
      immunohistochemistry on the 18th day of incubation, after macroscopic
      examination. The intestines were evaluated with light microscopy for the presence
      of mucosal congestion and muscular and serosal edema. Mean muscular thickness and
      density of ICC were measured. RESULTS: Mean muscular thickness significantly
      increased in the gastroschisis group when compared with control and treatment
      groups. Labeling intensity, morphology, and localization of the ICC were similar
      in all groups. Mean ICC density significantly decreased in the gastroschisis
      group when compared with the control group (P < .01), and it significantly
      increased after amnio-allantoic fluid exchange treatment (P < .01). CONCLUSIONS:
      The decrease in ICC density encountered in damaged intestinal loops in
      gastroschisis was prevented with intrauterine treatment. The beneficial effects
      of amniotic exchange on intestinal motility may depend on both prevention of
      intestinal damage and preservation of ICC density and function. The density of
      ICC might be a reliable numeric parameter both to predict intestinal motility
      disorders in gastroschisis and to compare the effectiveness of intrauterine
      treatment methods.

PMID- 17502184
TI  - Monitoring diagnostic accuracy and complications. A report from the Children's
      Oncology Group Hodgkin lymphoma study.
AB  - BACKGROUND/PURPOSE: Cancer studies mandate quality assurance programs for
      clinical trials. Surgeons consistently play 2 roles early in the management of
      Hodgkin lymphoma in children and adolescents: obtaining a specimen for pathologic
      diagnosis and placing a central venous catheter to assist with therapy delivery.
      A surgical quality assurance program was embedded as part of the of the Hodgkin
      lymphoma study (AHODOOO31) to assess diagnostic accuracy and complications.
      METHODS: Surgical checklists and operative and pathology reports were reviewed
      concurrently. Diagnostic technique, success rate, location of biopsy, combined
      procedures under one anesthetic, and complications are reported. RESULTS: One
      hundred eighty-five cases were reviewed, with 169 having complete data.
      Diagnostic techniques included open biopsy (n = 148), computed tomography-guided
      core biopsy (n = 5), thoracoscopic/laparoscopic biopsy (n = 10) and fine-needle
      aspirations (n = 4). No staging laparotomies were performed. Biopsy sites
      included cervical (133), mediastinal (18), axillary (7), and others (11).
      Diagnostic accuracy was 145 of 148 (98.5%) for the open biopsy; 4 of 5, core
      biopsy (80%); 6 of 10 (60%), thoracoscopic/laparoscopic biopsy; and 1 of 4, fine
      needle aspiration (25%). Eighteen had mediastinal disease only, 9 of whom had a
      thoracoscopic biopsy with a 55% diagnostic accuracy. Inadequate sample was the
      only reason for a lack of diagnosis. A second open operation was required in
      these cases for diagnosis. At biopsy, frozen section confirmed a malignancy in
      68. In 38 of these 68 children, a central line was placed during the same
      anesthetic. The most common complication was inadequate sampling. Three wound
      infections were reported. CONCLUSIONS: With an appropriate surgical approach to
      obtain an adequate tissue specimen, diagnostic accuracy is high and surgical
      complications are low in children with Hodgkin lymphoma. Diagnostic technique
      should ensure adequate tissue sampling especially when not using an open
      procedure. When possible, central line insertion should be performed under the
      same anesthetic. Fine-needle aspiration was not used enough to assess its role in
      the diagnosis of children with Hodgkin lymphoma.

PMID- 17502185
TI  - The contrast enema for Hirschsprung disease: predictors of a false-positive
      result.
AB  - PURPOSE: To examine predictors of a false-positive (FP) result on contrast enema
      (CE) for the diagnosis of Hirschsprung disease (HD). METHODS: Retrospective
      analysis, over a 5-year period (1999-2004), of infants (<6 months of age) with
      suspected HD undergoing rectal biopsy following abnormalities identified on CE
      (transition zone [TZ], abnormal rectosigmoid ratio, microcolon, retained
      contrast, or mucosal irregularity). RESULTS: One hundred twenty-nine patients
      underwent rectal biopsy following an abnormal CE. The FP rate was 48.5% (66 with
      HD). Age below 30 days (OR, 3.4; 95% CI, 1.1-10.3), female sex (OR, 3.4; 95% CI,
      1.6-7.3), and absence of TZ (OR, 6.3; 95% CI, 2.6-15.3) were independently
      associated with an increased risk for FP on multiple variable logistic
      regression. A history of bilious emesis decreased the probability of FP (OR, 0.2;
      95% CI, 0.06-0.5). CONCLUSIONS: Transition zone, sex, age, and bilious emesis are
      important predictors of FP in those with suspected HD and CE abnormalities. With
      100% incidence of FP, infants younger than 30 days with neither bilious emesis
      nor a TZ and female infants younger than 30 days with these features may
      represent a subpopulation in whom rectal biopsy can be avoided.

PMID- 17502186
TI  - Extrahepatic portal vein obstruction results in hepatocyte proliferation but a
      decrease in protein-C synthesis.
AB  - PURPOSE: Extrahepatic portal vein obstruction (EHPVO) results in decreased levels
      of liver-dependent coagulation factors in children. We developed a rat model to
      test the hypothesis that lower factor levels associated with EHPVO were from
      diminished synthesis rather than increased consumption. METHODS: A total of 8
      rats (experimental group) underwent narrowing of portal vein (PV) and 8 underwent
      sham operations. Liver and spleen mass, serum alanine aminotransferase,
      bilirubin, ammonia, prothrombin time, factor VII, and protein-C were measured
      before and 3 months after PV narrowing. Hepatocyte proliferation and apoptosis
      were quantified using Ki-67 and TUNEL assays. RESULTS: Portal vein diameter was
      71% +/- 13% narrower in experimental animals. Liver mass was unchanged, but
      proportional spleen mass was higher in the experimental group at 3 months (0.31%
      +/- 0.05% vs 0.26% +/- 0.04%; P < .05). Percent apoptotic cells at 3 months was
      similar in both groups (0.14% +/- 0.08% vs 0.13% +/- 0.07%), but percent
      proliferating cells was higher in the experimental group (0.63% +/- 0.17% vs
      0.34% +/- 0.11%; P < .05). Three-month protein-C levels decreased significantly
      only in the experimental group compared with preoperative values (12.8% +/- 4.4%
      vs 7.6% +/- 5.1%; P < .05). Changes in other parameters were not significant.
      CONCLUSIONS: Our EHPVO model consistently produced PV narrowing. The increase in
      hepatocyte proliferation seen after EHPVO suggests a liver repair response that
      is insufficient to maintain normal protein-C synthesis and serum levels.

PMID- 17502187
TI  - Ileal exclusion for refractory symptomatic cholestasis in Alagille syndrome.
AB  - BACKGROUND: Alagille syndrome (AGS) can result in pruritic self-mutilation and
      disabling or disfiguring xanthomas. Though external biliary diversion and
      transplantation have been described for AGS, few data exist for the use of ileal
      exclusion (IE) in this setting. METHODS: Three patients with AGS with symptomatic
      cholestasis despite maximal medical management underwent IE. In each case, small
      bowel length was measured and the terminal 15% of ileum was excluded using
      stapled division and ileocecal anastomosis. Symptom scores were collected after
      institutional review board approval and are presented here as mean (range).
      Pruritus and xanthomas were graded as follows: 0 = none, 1 = mild
      scratching/minimal, 2 = active scratching/moderate, 3 = abrasions/disfiguring, 4
      = mutilation/disabling. RESULTS: Mean follow-up was 30 months (4-45 months).
      Pruritus score decreased from 3.33 (3-4) to 0.33 (0-1). Xanthoma score decreased
      from 3.67 (3-4) to 1.67 (1-2). All patients were maintained on nutritional
      supplements pre- and postoperatively without a change in management. No patients
      experienced diarrhea or dehydration postoperatively. There were no complications.
      CONCLUSIONS: Ileal exclusion effectively decreases refractory pruritus and
      xanthoma burden in AGS. This procedure offers the advantages of reversibility,
      avoidance of a stoma, and technical ease. Ileal exclusion should be considered
      for symptomatic AGS refractory to medical management as an alternative to
      external biliary diversion or liver transplantation.

PMID- 17502188
TI  - Neonatal short bowel syndrome outcomes after the establishment of the first
      Canadian multidisciplinary intestinal rehabilitation program: preliminary
      experience.
AB  - BACKGROUND: A multidisciplinary intestinal rehabilitation team has been in place
      at our institution for 3 years. Our goal was to compare the preliminary outcomes
      of neonates with short bowel syndrome before with those after the establishment
      of our formalized intestinal failure program (Group for the Improvement of
      Intestinal Function and Treatment [GIFT]). METHODS: We conducted a retrospective
      analysis of our intestinal failure registry comparing preGIFT (1997-1999) with
      GIFT (2003-2005) outcomes. RESULTS: Fifty-four patients (mean gestational age =
      33.5 weeks) were included in the GIFT cohort, and 40 patients (mean gestational
      age = 30.7 weeks) formed the preGIFT cohort. Overall mortality rates (33.3% vs
      37.5%, P = .84) were equivalent in the 2 cohorts, although fewer patients died of
      liver failure after the establishment of the GIFT. Among those with liver
      failure, the mortality in the preGIFT group was 9/10 as compared with that of
      6/13 in the GIFT group (P = .03). The decrease in liver-related deaths was partly
      attributable to earlier referral for and increased survival to transplant (4 for
      the GIFT group vs 0 for the preGIFT group). CONCLUSIONS: Analysis of the
      preliminary outcomes of the GIFT program suggests that the natural history of
      neonatal short bowel syndrome remains unaltered to date despite a coordinated
      approach to care. However, improved communication and integration with the
      transplant service have resulted in earlier assessment, increased rates of
      transplantation, and decreased mortality from liver failure.

PMID- 17502189
TI  - A comparison of chest tubes versus bulb-suction drains in pediatric thoracic
      surgery.
AB  - BACKGROUND/PURPOSE: Chest tubes are commonly used to evacuate the pleural space
      of air and fluid after thoracic surgery. The safety and efficacy of postoperative
      traditional chest tubes (CTs) versus soft bulb-suction drains (BDs) in the
      management of pediatric patients undergoing thoracic procedures were
      investigated. METHODS: An institutional review board-approved, retrospective
      review was performed on all patients who required noncardiac, nontraumatic
      thoracic operations from January 2000 to December 2005. Patient data included BD
      or CT drainage, age at operation, indication for surgery, open or thoracoscopic
      approach, days of postoperative drainage, the development of a postremoval
      pneumothorax, and complications. Statistical comparisons were made using t test
      and chi2 test. RESULTS: During the study period, 186 patients with complete
      records underwent a thoracic operation. One hundred twenty (65%) received a CT,
      whereas 66 (35%) received a BD. Patients who received CT averaged 5.6 days of
      drainage compared with 4.4 days in the group that received BD. Postremoval
      pneumothorax developed in 5 (4%) patients with CT compared with 4 (6%) patients
      with BD. Two patients in the CT group required reinsertion of another CT. None of
      the BD patients required further intervention. CONCLUSION: For thoracoscopic and
      open thoracic operations, BDs are as safe and efficacious as traditional CT.

PMID- 17502190
TI  - Postnatal outcome in gastroschisis: effect of birth weight and gestational age.
AB  - INTRODUCTION: Early elective delivery of antenatally diagnosed gastroschisis has
      been proposed as a strategy to minimize postnatal morbidity. This hypothesis was
      tested by analyzing outcome in relationship to gestational age and birth weight
      at delivery. METHODS: Single-center retrospective review of infants born with
      gastroschisis over a 13-year period (January 1993-December 2005). Standard
      outcome measures were compared using nonparametric methods. Data are quoted as
      median values (range). RESULTS: The study population consisted of 110 infants
      with gastroschisis. They were divided according to gestational age (group A, <35
      weeks; group B, 35-37 weeks; group C, >37 weeks) and birth weight (group D, <2
      kg; group E, 2-2.5 kg; group F, >2.5 kg). Duration in hospital (P < .01) and time
      to full enteral feeding (P = .05) was increased in group A vs groups B and C. In
      comparison, duration in hospital (P < .01), days ventilated (P = .03),
      establishment of full feeds (P = .01), and parenteral nutrition (P = .02) were
      all prolonged in group D vs groups E and F. Six (5%) infants died (group D, n =
      3; group E, n = 3). Necrotizing enterocolitis was found in 7 infants, and
      confined to groups D and E (chi2 for trend P = .06). CONCLUSION: There is no
      evidence that prematurity confers an advantage in restitution of gastrointestinal
      function in infants with gastroschisis; indeed, the opposite appears true. Birth
      weight, rather than gestational age, appears a better predictor of outcome.

PMID- 17502191
TI  - The 2 STEP: an approach to repeating a serial transverse enteroplasty.
AB  - PURPOSE: The serial transverse enteroplasty procedure (STEP) procedure is a
      successful and safe approach to lengthen small bowel in patients with short bowel
      syndrome (SBS). However, postlengthening dilatation may occur, which can lead to
      bacterial overgrowth and malabsorption. We addressed this problem by reperforming
      the STEP in 2 patients. METHODS: Two infants underwent the STEP procedure at 3
      days and at 4 months of life for SBS secondary to intestinal atresia and
      gastroschisis. The patients' small bowel lengths were 20 and 32 cm before and 25
      and 52 cm after the initial STEP. Nine and 8.5 months afterward, the patients
      developed dilatation of the small bowel and feeding intolerance. A second STEP
      procedure was undertaken with additional transverse firings of staplers between
      previously lengthened segments and tapering of redundant blind-ending portions of
      bowel. RESULTS: At operation, the bowel lengths were 45 and 62 cm. The second
      STEP left the patients with 61 and 73 cm of small bowel with a normalization of
      intestinal diameter. The first patient is doing well 5 months after surgery, and
      the second child tolerated increased enteral intake but died 1 year later from
      total parenteral nutrition-related liver failure. CONCLUSIONS: This is the first
      report of a successful application of a second STEP procedure to further lengthen
      small bowel in SBS patients. Reapplication of the procedure requires careful
      stapling and a removal of small blind-ending segments to avoid further stasis.

PMID- 17502192
TI  - Comparative study between window and conventional enterostomies in preterm
      neonates with small bowel perforations.
AB  - OBJECTIVES: Small bowel perforations in the neonatal period can be secondary to
      necrotizing enterocolitis (NEC), ischemic necrosis, or occlusive anomalies of the
      small bowel; furthermore, they may be of no discernible cause. Depending on the
      clinical condition of the infant and the extent of the disease, a number of
      surgical options are available; one of which is exteriorization. To reduce the
      morbidity of stoma among patients, we adopted a technique called window
      enterostomy (WEnt). The objectives of this study were to describe the technique
      and to compare WEnt with conventional enterostomy (CEnt) in preterm infants
      undergoing surgery for focal NEC or isolated small bowel perforation (ISBP).
      METHODS: We reviewed all cases of NEC and ISBP between January 1996 and March
      2006 from our institution. Patients with focal NEC or ISBP who required a
      surgical intervention were included and categorized into the WEnt and the CEnt
      groups. We collected multiple data as study variables: demographics; site of
      perforation; operative time; need for a second operation; postoperative
      morbidity; duration of total parenteral nutrition; and postoperative weight gain.
      RESULTS: Twenty-four neonates met the criteria for study inclusion. Of these, 14
      underwent CEnt and 10 underwent WEnt. The median gestational age and birth weight
      of the neonates were 25.4 weeks (SD = 1.4) and 814.4 g (SD = 195.1),
      respectively. In comparing the 2 groups, we found statistically significant
      differences in the operative time for the primary and secondary procedures,
      duration of total parenteral nutrition, time to full oral feeding, and weekly
      postoperative weight gain. The rate of postoperative complications was higher
      among the infants from the CEnt group. CONCLUSION: Our results suggest that WEnt
      is a quick and workable technique with minimal morbidity for preterm neonates
      with focal NEC or ISBP.

PMID- 17502193
TI  - Retroperitoneal sarcomas in children: outcomes from an institution.
AB  - BACKGROUND: Retroperitoneal sarcomas are uncommon in children and tend to present
      as large tumors with advanced locoregional involvement of abdominopelvic
      structures. Surgical control of these tumors remains to be a management
      challenge. We reviewed our institutional experience with retroperitoneal sarcomas
      in children. MATERIALS AND METHODS: In a retrospective review of charts dating
      between 1975 and 2005, we identified patients younger than 18 years who were
      diagnosed with a histologically confirmed retroperitoneal sarcoma. Patients were
      followed prospectively through clinic visits and mail correspondence. Standard
      statistical methods were used for comparative, risk, and survival analyses.
      RESULTS: Twenty-one children with a mean age at presentation of 9 +/- 1 years
      were identified. There were more boys than girls (male/female ratio = 1.6). The
      most common presentations were abdominal mass/distention (76%) and pain (62%).
      The mean tumor size was 14.2 +/- 1.4 cm, with locoregional involvement in 62% of
      the patients. The common histologic types were rhabdomyosarcoma (33%) and
      fibrosarcoma (33%). Seventy-six percent of the patients underwent primary or
      secondary resection, 71% received neoadjuvant and/or adjuvant chemotherapy
      therapy, and 38% received radiation therapy. Complete resection was achieved in
      48% of the patients, including 3 who required inferior vena cava resection and
      reconstruction. The 5-year disease-specific survival rates for patients who
      underwent complete resection and those who underwent incomplete resection were
      90% and 36% (P = .018), respectively. For all patients, the mean survival time
      was 103 +/- 16 months and the 5-year disease-specific survival rate was 62%.
      Survival was significantly better for patients with low-grade sarcomas than for
      those with high-grade sarcomas (90% vs 36%, P = .008). Among those who underwent
      an initial complete resection, 50% had a recurrence at a mean time of 88 +/- 52
      months (range = 3-261 months). The 30-day postoperative mortality and morbidity
      rates were 0% and 24%, respectively; in addition, 14% of the patients experienced
      long-term complications. CONCLUSIONS: Resection of retroperitoneal sarcomas can
      be performed safely with minimal morbidity and mortality. Complete resection and
      low histologic grade are associated with significantly better disease-specific
      survival.

PMID- 17502194
TI  - Outcomes of primary liver cancer in children: an appraisal of experience.
AB  - INTRODUCTION: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most
      common primary liver cancers in children. Recent advances in management of
      pediatric liver cancer have improved disease-specific survival (DSS). This is a
      review of our experience with childhood liver malignancy over the past 3 decades.
      MATERIALS AND METHODS: A retrospective chart review from 1975 to 2005 identified
      patients who were 18 years old or younger with a histologically confirmed
      diagnosis of primary liver cancer. Patients were staged according to the
      Children's Cancer Group and Pediatric Oncology Group (CCG/POG) system. Patients
      were followed up prospectively through clinic visits and mail correspondence.
      Standard statistical methods were used for comparison, risk, and survival
      analyses. RESULTS: Fifty-two patients were confirmed to have primary liver
      cancers, where 24 (46%) patients had HB, 22 (42%) had HCC, 3 (6%) had sarcomas,
      and 3 (6%) had other histologies. Mean ages at presentation for HB and HCC were
      3.2 and 13.1 years old, respectively. The most common presentations were
      abdominal mass (67%) and pain (40%). Most patients underwent major liver
      resection (n = 45, 87%), including: lobectomy (n = 25, 48%), and trisegmentectomy
      (n = 11, 21%). Three patients underwent liver transplantation (n = 3, 6%) for
      advanced local disease. Forty-five (87%) received primary or neoadjuvant and/or
      adjuvant chemotherapy. Patients had the following CCG/POG stages: I (n = 31,
      60%), II (n = 6, 11.5%), III (n = 9, 17%), and IV (n = 6, 11.5%). Complete gross
      resection (stage I and II) was achieved in 37 (71%) patients. The perioperative
      mortality and morbidity rates were 0% and 29%, respectively. Patients with
      complete resection had significantly better 5-year DSS and median survival
      compared with incomplete gross resection: 62% vs 9% and 216 vs 18 months, P <
      .001. Patients treated during the period 1995-2005 had better 5-year DSS and
      median survival compared with those treated during 1975-1994: 68% vs 32% and 117
      vs 27 months, P = .032. All 3 patients who underwent transplantation for
      conventionally unresectable disease are alive without disease recurrence (follow
      up period, 1-15 years). CONCLUSION: Complete resection of the pediatric primary
      liver tumors remains the cornerstone of treatment to achieve cure. Major liver
      resection can be performed with minimal perioperative mortality and morbidity.
      Patients with HB appeared to have better survival compared with patients with
      HCC, and there was significant improvement in the DSS of children treated in the
      recent decade. Liver transplantation in conjunction with chemotherapy may have an
      increasing role in the management of locally advanced primary liver cancers.

PMID- 17502195
TI  - Ambiguous genitalia: an overview of 17 years' experience.
AB  - AIM: The newborn with abnormal genital development presents a difficult
      diagnostic and treatment challenge for the pediatric surgeon providing care. The
      purpose of this study was to evaluate the results of surgical treatment for
      children with ambiguous genitalia. PATIENTS AND METHODS: The records of 85
      children managed surgically for ambiguous genitalia in our unit from 1988 to 2005
      were reviewed retrospectively. Age at surgery, operative procedures, sex of
      rearing, and outcome were recorded. RESULTS: The intersex committee's decision
      concerning sex assignment was female for 62 children (75%) and male for 23
      children (25%). The etiologies of children reared as female were congenital
      adrenal hyperplasia (n = 37), male pseudohermaphroditism (n = 12), mixed gonadal
      dysgenesis (n = 6), true hermaphroditism (n = 4), and Mayer-Rokitansky syndrome
      (n = 3). Fifteen children with male pseudohermaphroditism, 5 children with
      congenital adrenal hyperplasia, and 3 children with true hermaphroditism were
      reared as male. The mean age at surgery was 4.4 years and follow-up period
      averaged 7 years. Eighteen (29%) patients with feminization procedures and 8
      (34%) of 23 patients with masculinization procedures experienced complications
      and required redo operations. Vaginal stenosis was the most common complication.
      CONCLUSION: The surgical management of ambiguous genitalia has always been
      difficult, and it must be performed by skilled pediatric surgeon. Genital surgery
      in infancy needs to be reassessed in the light of literature findings revealing
      poor outcome. In patients who underwent feminizing genitoplasty, vaginal
      reconstruction should be delayed until adolescence to achieve better cosmetic and
      functional results.

PMID- 17502196
TI  - Laparoscopic versus open reduction of intussusception in children: a single
      institution comparative experience.
AB  - BACKGROUND: The role of laparoscopic surgery in treating intussusception has been
      controversial. This study reviews our institution's experience with the
      laparoscopic approach (LAP) compared to the open surgical approach (OPEN).
      METHODS: Retrospective analysis of all patients undergoing surgery for
      intussusception at our center from January 2002 to February 2006. Statistical
      assessment included Student's t test and chi2 analysis. RESULTS: A total of 41
      patients required operation for intussusception (18 LAP, 23 OPEN). Mean age was
      22 months for LAP and 11 months for OPEN (P = .17). In the LAP group, 28% (5/18)
      were converted to an open procedure. Operative times and complications were not
      significantly different. Pathologic lead points were found in 33% (6/18) LAP and
      35% (8/23) OPEN patients (P = 1.0). Time to full feeds was significantly shorter
      (LAP vs OPEN: 3.4 +/- 2.7 vs 5.6 +/- 3.4 days, P = .02). Length of stay was
      shorter (LAP vs OPEN: 4.8 +/- 3.5 vs 9.1 +/- 7.5 days, P = .03). CONCLUSIONS:
      Intussusception can be treated safely and effectively using a LAP with a
      significant decrease in time to full feeds and length of stay. The LAP should be
      considered as the initial approach for stable patients with intussusception
      requiring operative intervention.

PMID- 17502197
TI  - Clinical algorithm and resource use in the management of children with minor head
      trauma.
AB  - PURPOSE: There are no clear guidelines for the management of minor head injury,
      including the use of skull x-rays and computed tomography (CT) scans of the head.
      This is reflected in clinical practice by a wide variability in imaging study use
      and by the fact that some patients are discharged home from the emergency room
      (ER), whereas others are admitted to the hospital with or without a period of
      observation before admission. To address this issue, we proposed and applied a
      new protocol for minor head injury at our institution. METHODS: Between January
      2004 and December 2005, 417 patients presented to the emergency department at our
      institution with minor head injury. All of them had fallen from less than 1 m.
      Every chart was retrospectively evaluated, and pertinent data were extracted.
      RESULTS: The mean age of the patients was 9.8 months (2 weeks to 32 months). One
      hundred fifty-three had a skull x-ray, and 13 had a CT scan of the head. Of the
      153 patients who had a skull x-ray, only 15 had a skull fracture. Of these 15
      patients, 3 also had a CT scan of the head that confirmed the diagnosis of skull
      fracture. Of the 13 CT scans that were done, only these 3 were positive. Eleven
      patients were kept in the ER for 6 hours for close observation, and 5 of these
      were eventually admitted. Overall, 8 patients were admitted to the hospital for
      observation. Of these 8 patients, 7 had a skull x-ray, from which 5 were
      positive. Only 2 of the admitted patients had a CT scan, and they were both
      positive for a skull fracture. One of the CT also demonstrated a subdural
      hematoma along with subarachnoid hemorrhage. These 2 patients also had a positive
      skull x-ray. None of the patients that were admitted had headaches or neurologic
      impairments. The mean age of the patients admitted was 3.8 months (2 weeks to 12
      months). The mean hospital stay was 1.2 days (1-3 days). CONCLUSION: Only 10% of
      the skull x-rays and CT scans were positive for a skull fracture, which led to an
      admission in half of these patients. The other half was mainly discharged from ER
      after being observed. Several patients underwent a skull x-ray that we feel was
      not necessary in the management of their minor head injury. For those who had a
      head CT scan, only one revealed additional information and none of them had an
      impact on the final management. Observation in the ER could have been reasonable
      for most cases.

PMID- 17502198
TI  - Cumulative doses of adjunct 131I treatment depend on location of residual thyroid
      tissue after total thyroidectomy in differentiated thyroid cancer.
AB  - PURPOSE: The aim of this study was to review the outcome after adjunct
      postoperative 131I therapy in patients with differentiated thyroid carcinoma
      (DTC) treated with total thyroidectomy (excluding medullary thyroid carcinoma).
      METHODS: Retrospective chart review: Management protocol is total thyroidectomy
      with cervical node sampling, 131I whole-body scan 3 weeks postoperatively to
      document residual thyroid tissue or metastatic lesions. Adjunct treatment
      consists of one or more 131I (100-200 mci/1.73 m2). Patients are considered
      disease free if 2 consecutive 131I whole-body scan are negative with undetectable
      thyroglobulin level. RESULTS: Twenty-one patients, 14 females and 7 males, with a
      mean age of 13.6 years were treated. Whole-body scan postoperatively revealed
      uptake in the thyroid bed (TB) in 10 patients, in cervical lymph nodes (CLN) in 9
      patients, and in CLN and lungs in 2 patients. Patients with residual uptake in TB
      received a significantly lesser dose of 131I (mean, 122 +/- 53 mci) than those
      with metastatic CLN (357 +/- 182 mci) (P < .004) (t test) or lung mets (523.5
      mci). With a mean follow-up of 7.8 years (range, 1-16 years), overall survival is
      100% but disease-free survival is 100%, 66%, and 0% respectively for patients
      with residual disease in TB, CLN, and lungs. CONCLUSION: Patient with residual
      thyroid tissue in the TB required a significantly lesser number of treatments and
      doses of 131I compared to patients with cervical node metastases with a 100%
      disease-free survival. The best management of immediate postoperative residual
      cervical nodes (surgical excision vs 131I) remains to be defined. The efficacy of
      131I therapy in patients with lung metastases remains controversial with complete
      remission unlikely.

PMID- 17502199
TI  - Appendicitis in the obese child.
AB  - BACKGROUND/PURPOSE: Little data exist that examine the surgical challenges of
      obese children. We hypothesize that obesity affects the presentation, diagnosis,
      surgery, and postoperative course in children with appendicitis. METHODS: Cases
      of all children treated for appendicitis over 6 years were reviewed
      retrospectively. Demographics, presentation, pathology, and hospital course were
      examined. RESULTS: A total of 282 cases were reviewed; 25 were moderately obese
      and 31 very obese (VO), which were defined, respectively, as greater than 1.5 and
      greater than 2 standard deviations above the standardized mean weight for age.
      Groups were similar in age, sex, presentation, use of ultrasound, and surgical
      management. Compared with the nonobese group, median operative time was higher in
      the VO group (63.5 vs 55.5 minutes; P = .028), with the association between
      obesity and longer operative time maintained when stratifying for
      perforated/nonperforated and open/laparoscopic cases. Almost twice as many VO
      children were in the hospital for more than 5 days (nonobese 23.6%, VO 40.0%
      [odds ratio, 2.2; 95% confidence interval, 0.99-4.8]). This association between
      obesity and longer length of stay was seen when stratifying for both perforated
      and nonperforated cases. In the perforated group, higher rates of postoperative
      wound infections and significantly longer times to full diet and ambulation
      likely contributed to these longer stays. CONCLUSIONS: Childhood obesity is
      associated with longer surgery and hospital stays and increased risk of
      postoperative infections. Obesity should be considered an important variable when
      looking at surgical outcomes in the pediatric population.

PMID- 17502200
TI  - Laparoscopic ovarian tissue preservation in young patients at risk for ovarian
      failure as a result of chemotherapy/irradiation for primary malignancy.
AB  - BACKGROUND: Aggressive chemotherapy/radiotherapy for cancer may cause gonadal
      failure in young female survivors. The putative aim of ovarian tissue
      cryopreservation is to restore fertility by transplantation of a patient's frozen
      thawed ovarian tissue or, further into the future, by in vitro maturation of
      frozen-thawed oocytes followed by in vitro fertilization. This report presents
      our early experience with ovarian tissue preservation in young patients. METHODS:
      We conducted a database review of the techniques and outcomes of the ethics board
      approved ovarian tissue cryopreservation procedures performed at our center since
      1998 for young girls with malignancy. RESULTS: The study group included 23
      patients (median age = 14 years) with various types of cancer (hematologic, bone,
      ovarian, or intracranial); 11 patients were scheduled for chemotherapy, 11
      patients had already undergone some form of chemotherapy before the ovarian
      tissue harvesting, and 1 patient was not scheduled for chemotherapy. Ten
      underwent bone marrow transplantation after tissue retrieval. Twenty-one patients
      underwent laparoscopic harvesting of their ovarian tissue. In the other 2
      patients, the ovary was preserved during inguinal hernia repair or tissue was
      obtained at laparotomy for a pelvic tumor. All patients had benign operative and
      postoperative courses. CONCLUSIONS: Laparoscopy for ovarian tissue retrieval for
      cryopreservation is safe in young cancer patients. Based on reports of successful
      cryopreservation of human ovarian tissue containing primordial follicles, we
      believe that this approach holds promise for female cancer survivors.

PMID- 17502201
TI  - Evaluation of surgical approaches to pyloromyotomy: a single-center experience.
AB  - BACKGROUND: This study was conducted to evaluate the outcome of various
      approaches to pyloromyotomy: supraumbilical (SU), right upper quadrant (RUQ), and
      laparoscopic (LP). METHODS: Single-center retrospective review from 1998 to 2005
      with institutional review board approval, evaluating 192 pyloromyotomies based on
      surgical approach: RUQ (119), SU (64), and LP (9). Patient demographics, acid
      base/electrolyte status on presentation, mean operative time, postoperative
      length of stay, and complications were evaluated. RESULTS: Patient demographics,
      acid-base/electrolyte status, and mean operative time were not significantly
      different. The median length of stay was 34, 29, and 24.5 hours for SU, RUQ, and
      LP, respectively (P = .479). The frequency of duodenal/gastric perforations in
      the SU, RUQ, and LP groups were 1, 4, and 1, respectively. The LP perforation was
      not recognized intraoperatively, resulting in sepsis and multiorgan failure. One
      patient in the SU group had a late adhesive bowel obstruction requiring
      laparotomy and bowel resection. Wound infection rates did not differ
      significantly between groups (SU, 4; RUQ, 2; LP, 1; P = .113). CONCLUSION:
      Pyloromyotomy is associated with a low complication rate. Cosmetically, SU is
      superior to the RUQ approach. The added benefits of being able to examine the
      integrity of the duodenal mucosa intraoperatively and its short learning curve
      may make SU a safer alternative to LP for surgeons who are still practicing the
      RUQ approach.

PMID- 17502202
TI  - A role for laparoscopic approach in the treatment of biliary atresia and
      choledochal cysts.
AB  - BACKGROUND/PURPOSE: Indications for a laparoscopic approach in the management of
      biliary atresia and choledochal cysts in children are not clearly defined. We
      present our initial experience with 9 consecutive laparoscopic cases, and compare
      them to the traditional open approach. METHODS: A retrospective comparison of all
      consecutive operations for biliary atresia and choledochal cysts from January
      2000 to May 2006 was undertaken. We evaluated the patient's age at operation,
      operative time, return of bowel function postoperatively, length of hospital
      stay, complications, and the need for subsequent liver transplantation. Mann
      Whitney U test was used for statistical analysis. RESULTS: A total of 45
      portoenterostomies and choledochojejunostomies were performed, including 9
      laparoscopic and 36 open procedures. Patients with choledochal cysts were older
      than patients with biliary atresia. All the compared parameters were similar and
      there was no difference in outcomes between the laparoscopic and the open groups.
      CONCLUSIONS: Our initial experience is encouraging and indicates that the
      laparoscopic approach is technically feasible, safe, and effective, with a low
      morbidity and a comparable outcome to the open technique. Longer follow-up of a
      larger patient cohort is needed.

PMID- 17502203
TI  - Cholestasis associated with small bowel atresia: do we always need to
      investigate?
AB  - BACKGROUND/PURPOSE: Cholestasis occurs frequently in patients with small bowel
      atresia (SBA) and is often attributed to prolonged parental nutrition. When
      severe or prolonged, patients may undergo unnecessary intensive or invasive
      investigation. We characterized cholestasis and analyzed the pertinence of
      investigating this patient population. METHODS: With Research Ethics Board
      approval, patients with SBA between 1996 and 2005 were retrospectively reviewed.
      Demographics, location of atresia, operative findings, complications,
      investigations, resumption of feeding, duration of prolonged parental nutrition,
      and follow-up information were examined. Cholestasis was evaluated for incidence,
      severity, and evolution. RESULTS: Fifty-five patients (29 male, 26 female), with
      a median gestational age and birth weight of 36 weeks and 2025 g, respectively,
      were reviewed. Care was withdrawn for 2 patients before repair. For the remaining
      53 patients, SBA were duodenal atresia in 18, jejunoileal atresia in 32, and
      multiple atresia in 3. Of 53, 24 (45%) patients developed cholestasis
      postoperatively (direct/total bilirubin >20%). All patients with short bowel (4)
      and 60% (6/10) of patients with a delay of enteral feeding more than 14 days
      postoperatively had cholestasis. Ten patients (36%) proceeded with in-depth
      evaluations for cholestasis, with 8 (28%) undergoing liver biopsy. No patient had
      biliary atresia. No deaths were related to isolated cholestasis/cirrhosis.
      Cholestasis resolved spontaneously in all the survivors. CONCLUSIONS: Small bowel
      atresia is frequently associated with postoperative cholestasis that will resolve
      with time. We recommend a more selective and expectant approach to SBA-associated
      cholestasis to minimize unnecessary investigations.

PMID- 17502204
TI  - Canada-trained pediatric surgeons: a cross-border survey of satisfaction and
      preferences.
AB  - OBJECTIVES: The American and Canadian health care delivery systems impact
      pediatric surgical practice differently. We conducted a survey of Canada-trained
      pediatric surgeons practicing in the United States and Canada to compare their
      levels of satisfaction and to assess their health care system preferences.
      METHODS: Pediatric surgeons who graduated from Canadian training programs between
      1983 and 2002 were invited to complete a web-based questionnaire. They rated
      their satisfaction on a scale ranging from 1 (most) to 5 (least) with issues
      pertaining to quality of life, compensation, work environment, academics, and
      patient care. Surgeons who had experience in both the American and Canadian
      systems marked their preferences for each system as it impacted the same areas.
      RESULTS: Sixty surgeons (65% practicing in the United States and 35% in Canada)
      of 94 eligible participants (64%) responded to the survey. Surgeons in the United
      States were more satisfied with their overall workload and patient care issues,
      whereas those in Canada were more satisfied with the system of health care
      reimbursement and the medicolegal environment. Among 38 surgeons who had
      experience in both systems, 26% had an overall preference for the Canadian
      system, 24% did for the American system, and half had no preference. CONCLUSIONS:
      Canada-trained pediatric surgeons practicing in the United States are more
      satisfied with patient care issues, whereas those practicing in Canada are more
      satisfied with the medicolegal environment and the system of health care
      reimbursement. There is no overwhelming preference for either system among
      surgeons who had experience in both.

PMID- 17502205
TI  - Postoperative Hirschsprung's enterocolitis after minimally invasive Swenson's
      procedure.
AB  - BACKGROUND/PURPOSE: Our preferred minimally invasive technique of Swenson's
      procedure has evolved from laparoscopic (LapSwen) to Swenson's transanal
      pullthrough (SWAP). We studied the incidence of postoperative Hirschsprung's
      enterocolitis (HEC) over the past decade. METHODS AND MATERIALS: We
      retrospectively reviewed the charts of 52 children who had a primary Swenson's
      pullthrough procedure between 1995 and 2006. Two cohorts (25 LapSwen [1995-2000]
      and 27 SWAP [1998-2006]) were compared. RESULTS: Median ages of diagnosis were 13
      days for LapSwen and 4 days for SWAP. Median age at surgery was 4.1 months for
      LapSwen and 3.3 months for SWAP. Postoperative HEC occurred in 12% (16% LapSwen,
      7.4% SWAP). The incidence of Down's syndrome and preoperative HEC did not differ
      between the 2 cohorts. Three children with HEC were Clostridium difficile
      positive. Long-term function in the 36 children older than 4 years was excellent
      in 22%, good in 50%, fair in 11% and poor in 17%. CONCLUSION: Our incidence of
      postoperative HEC is low, and we have seen a trend toward fewer cases after the
      SWAP procedure. Early diagnosis, preoperative rectal irrigations, and routine
      postoperative anal dilatation may be contributing to the elimination of HEC as a
      significant risk after surgery for Hirschsprung's disease.

PMID- 17502206
TI  - Excision of large cystic ovarian tumors: combining minimal invasive surgery
      techniques and cancer surgery--the best of both worlds.
AB  - BACKGROUND/PURPOSE: Cystic ovarian lesions can be massive, and preoperative
      evaluations can often not distinguish benign from malignant tumors. Up to 57% of
      malignant ovarian tumors have a cystic component. We present an approach to these
      neoplasms that adheres to oncologic principles using minimally invasive
      techniques. METHODS: A 5-cm Pfannensteil incision is performed followed by
      peritoneal washings. The mass is identified and dried. Dermabond (Ethicon,
      Johnson & Johnson, New Jersey) is applied to an area of the capsule (measuring 3
      x 3 cm) and to a sterile plastic ultrasound bag. The bag is then applied directly
      to the exposed capsule. BioGlue (Cyrolife Inc, Kennesaw, GA) is then injected
      into and around the bag/mass interface and allowed to solidify. A veress needle
      decompresses the cyst, and the ovary is delivered out of the peritoneal cavity
      for either cystectomy or an oophorectomy. Routine surveillance of the omentum,
      lymph nodes, contralateral ovary, and peritoneal surface is then performed.
      RESULTS: Nine female patients (mean age, 14.1 +/- 2 years) were treated. All had
      normal alpha-fetoprotein and human chorionic gonadotropin. Computed tomographic
      scans demonstrated cystic lesions ranging from 8.9 to 27 cm in diameter (17.1 +/-
      2.6 cm2). Operative procedures were: 4 salpingooophorectomies and 5 unilateral
      oophorectomies. In a single case, the contralateral ovary had a suspicious
      lesion, which was biopsied. No tumors spills occurred. The pathology included 2
      simple cysts, 3 serous cyst adenomas, 3 mature cystic teratomas, and 1 immature
      teratoma with grade 2 to 3 immature elements. Peritoneal washings were negative.
      All patients were discharged within 48 hours and are well 15 months to 3.1 years
      postoperatively. CONCLUSIONS: The containment of the ovarian cyst with the
      application of surgical adhesives and a plastic sleeve offers a significant
      advancement in our ability to safely treat these lesions. This approach markedly
      reduces the length of the surgical incision while insuring the prevention of
      peritoneal contamination with cystic fluid.

PMID- 17502207
TI  - Laparoscopic adjustable gastric banding in adolescent: safety and efficacy.
AB  - BACKGROUND: Obesity prevalence is rapidly increasing among children and
      adolescents worldwide. It is considered one of the most alarming public health
      issues facing the world today. The adult experience has demonstrated that surgery
      is the only effective means of achieving persistent weight loss in obese
      patients. However, little is known about bariatric surgery in children and
      adolescents. The aim of this study is to evaluate the safety and efficacy of
      laparoscopic adjustable gastric banding (LAGB) in this group of patients.
      METHODS: A retrospective review included all children and adolescents who
      underwent LAGB from January 2003 to December 2005. RESULTS: Fifty-one patients
      underwent LAGB. The mean age was 16.8 years (range, 9-19), and the mean body mass
      index was 49.9 kg/m2 (range, 38-63). Mean excess weight loss was 42% at 6 months
      and 60% at 1 year follow-up. The most prevalent comorbidities were obstructive
      sleep apnea, limited physical activities, hypertension, and diabetes mellitus.
      Band adjustments were performed under fluoroscopic guidance in 5 patients and
      direct access as a clinic procedure in the remaining. One patient required port
      repositioning under fluoroscopic guidance. The mean follow-up was 16 months
      (range, 3-34). There was no mortality or significant postoperative complications.
      CONCLUSION: The absence of significant nutritional deficiency, the continued
      adjustability, and potential reversibility of LAGB make it the safest, least
      invasive, and most effective bariatric surgery that can be offered to the young
      and adolescent population.

PMID- 17502208
TI  - Clinical impact of optical imaging with 3-D reconstruction of torso topography in
      common anterior chest wall anomalies.
AB  - BACKGROUND: Standard modalities to assist in determining the extent of chest wall
      developmental deformities in patients include x-ray and computed tomography (CT).
      The purpose of this study is to describe an optical imaging technique that
      provides accurate cross-sectional images of the chest, and to compare these with
      standard CT-derived images of chest wall abnormalities. PATIENTS AND METHODS: Ten
      patients (5 pectus excavatum and 5 pectus carinatum) underwent imaging that
      included limited CT and optical cross-sectional imaging. Severity indices of the
      deformity using the standard Haller index (HI) were calculated from CT scans. A
      similar severity measurement of deformity was derived from the outline of torso
      cross sections (ie, from skin to skin measurements) obtained from optical images.
      To assess the severity of carinatum defects, a modified pectus index was derived,
      which measures the anterior chest protrusion from the central chord of the chest
      cross section. We performed regression analyses, comparing the indices obtained
      from CT and optical imaging methodologies. RESULTS: Optical measures of cross
      sectional deformities correlated well with standard HI (r2 = 0.94) and even
      better with the modified pectus index (r2 = 0.96). Adaptation of the HI for
      pectus carinatum deformity evaluation was effective, and consistent with the
      torso surface deformity measures. CONCLUSIONS: Torso models from optical imaging
      offer 3-D images of the chest wall deformity with no radiation exposure. This
      preliminary study showed promising results for the use of torso surface
      measurement as an alternative index of pectus deformities; if validated in larger
      studies, these measures may be useful for following chest wall abnormalities,
      using repeated studies in patients.

PMID- 17502210
TI  - Appendicitis and malrotation.
AB  - A 13-year-old child was admitted with abdominal pain suggesting acute
      appendicitis, but with some atypical findings. A computed tomography scan showed
      an inflamed appendix and fecalith in the central abdomen, and malrotation. These
      striking images both established the diagnoses and were useful in planning the
      operative approach.

PMID- 17502211
TI  - "Conservative management of necrotizing fasciitis in children".

PMID- 17502214
TI  - Impact of obesity on radiology.
AB  - Obesity is impacting radiology departments throughout the country. Increasingly,
      the ability to acquire and interpret images is compromised by a patient's body
      habitus. This article provides radiologists with background information about
      obesity including the definition of obesity, the prevalence of obesity, and the
      health and economic implications; describes current problems and provides
      specific solutions related to imaging obese patients using various modalities;
      and discusses the future of medical imaging and obesity.

PMID- 17502215
TI  - Imaging evaluation following Roux-en-Y gastric bypass surgery for morbid obesity.
AB  - As morbid obesity continues to increase in prevalence, bariatric surgery has
      become a popular treatment option. Radiologists must be aware of how to perform
      and interpret studies in this patient population. This article discusses the Roux
      en-Y gastric bypass procedure including the expected postoperative findings on
      upper gastrointestinal examinations and CT and the potential complications that
      may occur.

PMID- 17502216
TI  - Adjustable laparoscopic gastric banding for morbid obesity: imaging assessment
      and complications.
AB  - Laparoscopic adjustable gastric banding (LAGB) is a safe and effective means of
      weight loss for patients who have morbid obesity. LAGB currently is the least
      invasive surgical treatment for morbid obesity. Radiologists must be aware of the
      expected postoperative imaging findings, the optimal technique for radiologic
      assessment, and the postoperative complications that may occur. In addition,
      because band-adjustment procedures often are performed fluoroscopically, the
      radiologist may play a direct role in the management of weight loss in patients
      following LAGB.

PMID- 17502217
TI  - Multidetector CT angiography in the diagnosis of mesenteric ischemia.
AB  - Multidetector CT is an ideal tool for the diagnosis of acute and chronic
      mesenteric ischemia. Advanced CT scanners and expertise in three-dimensional
      imaging are becoming increasingly widespread, opening the door to new
      opportunities and challenges in the evaluation of patients suspected of having
      mesenteric ischemia. This article reviews contrast administration and image
      acquisition protocols, the anatomy of the mesenteric vasculature, the etiology of
      acute and chronic mesenteric ischemia, and CT findings diagnostic for these
      conditions.

PMID- 17502218
TI  - CT enteroclysis: techniques and applications.
AB  - CT enteroclysis overcomes the individual deficiencies of both barium enteroclysis
      and conventional CT and combines the advantages of both into one technique whose
      clinical applicability has been simplified and made more reliable with
      multidetector CT technology. This article examines the techniques of CT
      enteroclysis and presents an overview of its clinical applications relative to
      other methods of small bowel imaging.

PMID- 17502219
TI  - CT enterography: noninvasive evaluation of Crohn's disease and obscure
      gastrointestinal bleed.
AB  - CT enterography (CTE) is a noninvasive imaging test using neutral intraluminal
      contrast and intravenous contrast to evaluate the small bowel. Multiphasic
      imaging is used in evaluating obscure gastrointestinal bleeding (OGIB), and
      single-phase enteric imaging is used for all other indications, including Crohn's
      disease (CD). CTE findings of CD include bowel wall thickening, mucosal
      hyperenhancement, and mural stratification. CTE findings of angiodyplasias
      include a vascular tuft visible during arterial phase and an early draining
      mesenteric vein. Early studies indicate that CTE is superior to barium
      examination in the evaluation of CD and is complementary to capsule endoscopy in
      the evaluation of OGIB.

PMID- 17502220
TI  - MR imaging of the small bowel.
AB  - Cross-sectional imaging techniques such as CT and MR imaging have advantages over
      traditional barium fluoroscopic techniques in their ability to visualize
      superimposed bowel loops better and to improve visualization of extraluminal
      findings and complications. This article discusses MR imaging of the small bowel
      with enterography and enteroclysis techniques. It reviews the advantages,
      limitations, technique, and indications and reviews the results that have been
      obtained in evaluating different disease processes.

PMID- 17502221
TI  - Virtual colonoscopy: technique and accuracy.
AB  - Virtual colonoscopy (VC) has acquired an important role in evaluation of the
      colon. In some situations it may be a safer method to visualize the colon
      effectively, or it may be the only available option when other techniques have
      failed. This article reviews state-of-the art VC technique and the results of
      current performance trials. It discusses the rationale for using various colonic
      cleansing regimens for VC. It also discusses the two distending agents for VC
      (room air and carbon dioxide) and presents practical tips for administration and
      the role of antispasmodic drugs.

PMID- 17502222
TI  - CT colonography: visualization methods, interpretation, and pitfalls.
AB  - Virtual colonoscopy interpretation is improving rapidly with the development of
      efficient software using two-dimensional, three-dimensional (3D) endoluminal, and
      3D novel views such as those that seem to cut the colon open and lay it flat for
      interpretation. Comparison of these various views, comparisons of supine and
      prone positioning, and comparisons of lung and soft tissue windows aid in the
      recognition of various pitfalls of interpretation.

PMID- 17502223
TI  - CT colonography (virtual colonoscopy): a practical approach for population
      screening.
AB  - CT colonography (CTC), also known as virtual colonoscopy, is a minimally invasive
      test for the detection of colorectal polyps and masses. At the authors'
      institution, asymptomatic screening has been the overwhelming indication for CTC
      referral since local third-party coverage was initiated in April 2004. This
      practical review details the authors' current approach to CTC screening, which
      has evolved and matured over time. It discusses the entire spectrum from program
      set-up through patient disposition following CTC examination. The authors hope
      this article will provide a roadmap for radiologists who wish to institute a CTC
      screening program.

PMID- 17502224
TI  - MR colonography.
AB  - Combining the advantages of unsurpassed soft tissue contrast and lack of ionizing
      radiation, MR imaging of the gastrointestinal tract has become increasingly used
      clinically. Both bowel inflammation and tumor disease of the large bowel can be
      well visualized by means of MR colonography (MRC). This article describes current
      techniques of MRC and gives an overview of its clinical outcome. Special focus is
      directed toward the evaluation of patients' acceptance of MRC.

PMID- 17502225
TI  - Role of tight junctions in cell proliferation and cancer.
AB  - The acquisition of a cancerous phenotype by epithelial cells involves the
      disruption of intercellular adhesions. The reorganization of the E-cadherin/beta
      catenin complex in adherens junctions during cell transformation is widely
      recognized. Instead the implication of tight junctions (TJs) in this process is
      starting to be unraveled. The aim of this article is to review the role of TJ
      proteins in cell proliferation and cancer.

PMID- 17502227
TI  - Global epidemiology of HIV-AIDS.
AB  - Although intravenous drug use is the major route of transmission in several
      countries, sexual transmission is the dominant mode of HIV spread globally, with
      a concomitant epidemic in infants borne to HIV-infected mothers. The HIV epidemic
      varies substantially from one geographic area to another, and three broad
      epidemic categories describe the diversity of features observed globally: low
      epidemic settings, centrzated epidemics, and generalized epidemics. The
      introduction of highly active antiretroviral therapy in industrialized countries
      has transformed AIDS from an inevitably fatal condition to a chronic, treatable
      condition, but this goal has yet to be realized in most resource-constrained
      settings that bear a disproportionate burden of infection. This article describes
      the modes of HIV transmission, geographic distribution of the evolving AIDS
      pandemic, and case studies of each of the three types of HIV epidemics, and
      presents global trends in AIDS and mortality.

PMID- 17502228
TI  - Diagnosis and management of acute HIV infection.
AB  - HIV infection starts as an acute, systemic infection, followed by a chronic
      period of clinical latency, usually lasting 3 to 10 years, which precedes the
      eventual collapse of the immune system. It is increasingly recognized that events
      occurring during acute HIV infection may determine the natural course of the
      disease. The very dynamic events of acute HIV infection provide multiple
      opportunities for biologic interventions, such as anti-retroviral or immune-based
      therapies. Similarly, the implementation of public health measures during acute
      HIV infection could help control epidemics or outbreaks. Many of the dramatic
      possibilities for intervention in acute HIV infection remain unproved, not the
      least because of traditional difficulty of diagnosing patients during this early
      period. This article reviews the natural history, pathogenesis and clinical
      presentation of acute HIV infection, and suggests a diagnostic and therapeutic
      approach to guide clinicians dealing with patients with suspected or confirmed
      acute HIV infection.

PMID- 17502229
TI  - Primary care issues for HIV-infected patients.
AB  - HIV primary care is determined by the intersection of the unique aspects of the
      infection and its treatment, the unique aspects of the populations affected by
      HIV, and the challenges of disease prevention and health maintenance in the
      general population. Any primary care provider may be called on to care for a
      patient living with HIV, and it is incumbent on all medical providers to become
      proficient in the management of this complex infection. This proficiency includes
      an awareness of local resources for referral, including medical and surgical
      specialists, mental health providers, and social service organizations. Given the
      complexity of HIV care in the twenty-first century and the potential for
      involvement of multiple consultants, the role of primary care provider is perhaps
      more critical for the HIV-infected patient than for the average patient.

PMID- 17502230
TI  - Antiretroviral management of treatment-naive patients.
AB  - Antiretroviral management of treatment-naive patients begins with the decision of
      when to start treatment. Current treatment guidelines suggest starting therapy in
      anyone with AIDS, HIV-related symptoms, or a CD4 cell count less than 200/mm3
      regardless of symptoms. Starting treatment in asymptomatic patients with CD4 of
      more than 200 requires consideration of a number of pros and cons, and
      individualization is the key. Recommended first-line antiretroviral regimens
      consist of two nucleoside reverse transcriptase inhibitors together with either a
      nonnucleoside reverse transcriptase inhibitor or a protease inhibitor (with or
      without ritonavir boosting). The goal of antiretroviral therapy is maximally to
      suppress viremia, enhance or improve immune function, and prevent clinical
      progression.

PMID- 17502231
TI  - Approach to the treatment-experienced patient.
AB  - The management of treatment-experienced patients is complex and challenging.
      Fortunately, new agents continue to be developed that offer hope to those who
      have developed resistance to currently available agents. Knowing when, how, and
      in whom to use new agents is never easy and highlights the importance of expert
      care for HIV-infected patients. The management of treatment-experienced patients
      requires considerable expertise, especially now that patients with highly
      resistant virus can hope to achieve full virologic suppression.

PMID- 17502232
TI  - Management of antiretroviral treatment-related complications.
AB  - Antiretroviral therapy for HIV restores immune function, controls viral
      replication, decreases opportunistic infections, and extends lifespan to near
      normal for infected individuals. However, successful HIV therapy has been
      accompanied by the emergence of treatment-related complications, with an impact
      not yet fully understood. This article reviews six common complications of
      antiretroviral therapy, including hyperlactatemia/lactic acidosis,
      hypersensitivity reactions, abnormal glucose metabolism, dyslipidemia, body
      composition changes, and cardiovascular disease. A comprehensive approach to
      management of antiretroviral-related complications includes awareness of (1) risk
      factors for adverse reactions, (2) clinical syndromes suggestive of an evolving
      complication, and (3) evidence-based monitoring and treatment strategies. Fluency
      in options for preventing and managing complications can provide maximal
      opportunity to balance treatment effects with quality of life.

PMID- 17502233
TI  - Special care issues of women living with HIV-AIDS.
AB  - Many HIV-infected women are benefiting from highly active antiretroviral therapy
      and living longer. Their reproductive choices vary over the life cycle, and there
      is a need to understand the appropriate contraceptives for those not intending
      pregnancy. There are specific gynecologic issues relevant to HIV-infected women,
      such as genital tract infections, risk for cervical cancer, and menstrual
      irregularities. More women are expected to reach menopause. Health care providers
      should be aware of these unique needs of HIV-infected women.

PMID- 17502235
TI  - Behavioral aspects of HIV care: adherence, depression, substance use, and HIV
      transmission behaviors.
AB  - A variety of psychosocial stressors are involved in living with HIV, maintaining
      a regimen of highly active antiretroviral therapy, and negotiating necessary self
      care behaviors. Because health care providers are in regular contact with HIV
      infected individuals in care, these contacts allow for the opportunity to assess
      and intervene on important variables related to quality of life and HIV outcomes.
      This article reviews information about four important behavioral aspects of HIV
      care: treatment adherence, depression, high-risk sex, and substance abuse.
      Efforts by health care providers to address these factors may result in better
      treatment outcomes, enhanced quality of life among HIV patients, and decreased
      HIV transmission.

PMID- 17502236
TI  - HIV vaccine efficacy trials: towards the future of HIV prevention.
AB  - Past efficacy trials of HIV vaccines have attempted to generate neutralizing
      antibodies. With the failure of these trials to demonstrate protection, the focus
      for HIV vaccine development has shifted to inducing a cytotoxic T-lymphocyte
      response (CTL). A CTL response is not expected to produce sterilizing immunity,
      but may delay progression to AIDS or reduce the transmission of HIV. Adenovirus
      vector-based regimens that induce CTLs are currently in efficacy trial testing.
      These efficacy trials are using surrogate end points in an innovative Phase 2B
      trial design.

PMID- 17502234
TI  - Clinical care of the HIV-infected drug user.
AB  - HIV/AIDS and chemical dependency, the latter often intertwined with mental
      illness, are complex, overlapping spheres that adversely influence each other and
      the overall clinical outcomes of the affected individual. Each disorder
      individually impact tens of millions of people adversely, with explosive
      epidemics described worldwide. This article addresses the adverse consequences of
      HIV/AIDS, drug injection, the secondary comorbidities of both, and the impact of
      immunosuppression on presentation of disease as well as approaches to managing
      the HIV-infected drug user.

PMID- 17502237
TI  - The future of HIV prevention: prospects for an effective anti-HIV microbicide.
AB  - Topical microbicides are self-administered products for prevention of HIV
      transmission, and they present one of the most promising strategies for combating
      the HIV-AIDS epidemic. The development of microbicides is a long and complicated
      process, with many hurdles that are unique to this class of product, including
      challenges in product design, in the conduct and design of clinical trials, and
      in obtaining licensure of a new class of products intended for use almost
      exclusively in developing countries. Once they have been registered, there are
      additional challenges to the marketing and distribution of microbicides. An
      overview of the types of microbicide currently in development, and a summary of
      the issues and the approaches being taken to address them, are provided.

PMID- 17502239
TI  - Structural analysis of supramolecular assemblies by hybrid methods.

PMID- 17502238
TI  - The future of HIV prevention: control of sexually transmitted infections and
      circumcision interventions.
AB  - Prevention and control of sexually transmitted infections (STIs) has proven
      effective in reducing HIV infection when treatment is available promptly for
      symptomatic persons in conditions of an emerging epidemic. Biologically, it is
      assumed that reduced genital tract inflammation reduces infectiousness for HIV as
      well as reducing susceptibility in HIV-uninfected persons. Male circumcision has
      been demonstrated effective in reducing risk for HIV infection in three separate
      trials from South Africa, Kenya, and Uganda. Global expansion of STI treatment
      and male circumcision programs are vital tools for control of HIV infection;
      current evidence is reviewed and research priorities are presented.

PMID- 17502240
TI  - Looking into live cells with in-cell NMR spectroscopy.
AB  - In-cell NMR spectroscopy has gained recent popularity since it provides means to
      analyze the conformational and functional properties of proteins inside living
      cells and at atomic resolution. High-resolution in-cell NMR spectroscopy was
      originally established in bacterial cells and based on a rationale that relies on
      protein over-expression and sample analysis within the same cellular environment.
      Here, we review in-cell NMR approaches in Xenopus laevis oocytes and evaluate
      potential future applications in other eukaryotic cell types.

PMID- 17502241
TI  - A promising technique for transplantation of bone marrow-derived endothelial
      progenitor cells into rat heart.
AB  - OBJECTIVE: To investigate the feasibility of intracoronary application of
      endothelial progenitor cells and the subsequent distribution within the heart.
      METHODS: Endothelial progenitors cells (EPCs) cultured from rat bone marrow were
      identified by double-positive staining with Dil-Ac-LDL and BS1-lectin. Twenty
      four hours before cell transplantation, EPCs were labeled with 5-bromo-2'
      deoxyuridine (BrdU). Cells (5 x 10(5) in 250-microl medium) were injected into
      healthy rats, either as intracoronary application (n=11) or as intramyocardial
      injection (n = 6). At 15 min or 3 days posttransplantation, hearts as well as
      other organs (lung, liver, kidney, and spleen) were collected and processed for
      subsequent BrdU immunohistochemistry. The number of BrdU-positive cells per
      tissue area was counted. RESULTS: Compared to intramyocardial injection,
      intracoronary administration resulted in more than twice as much positive cells
      in the heart (P < .05), with no local differences within the heart. Whereas after
      15 min, EPCs were equally distributed in all examined organs (except for the
      spleen), cells that were still present after 3 days, approximately 10%, were
      selectively restricted to the heart. CONCLUSIONS: Our data indicate that the
      intracoronary application provides a promising technique for EPC transplantation
      in the rat heart.

PMID- 17502242
TI  - HMGB1 expression by activated vascular smooth muscle cells in advanced human
      atherosclerosis plaques.
AB  - BACKGROUND: Chronic inflammation plays a key role in atherogenesis, which is
      followed by atheromatous plaque instability. High-mobility group box 1 is
      released by activated macrophages as a late-phase mediator during prolonged
      inflammation. However, the expression of high-mobility group box 1 and its effect
      on the production of C-reactive protein and matrix metalloproteinases,
      particularly on human vascular smooth muscle cells, still remain unknown. METHODS
      AND RESULTS: Immunohistochemical studies revealed that high-mobility group box 1
      was abundantly expressed in vascular smooth muscle cells of carotid and coronary
      atheromatous plaques, but not in atrophic vascular smooth muscle cells of fibrous
      plaques and normal medial vascular smooth muscle cells. Receptor for advanced
      glycation end products was also detected in vascular smooth muscle cells positive
      for high-mobility group box 1. Moreover, vascular smooth muscle cells positive
      for high-mobility group box 1 were found to express both C-reactive protein and
      matrix metalloproteinases (2, 3, and 9). Administration of exogenous high
      mobility group box 1 to cultured vascular smooth muscle cells caused a marked
      elevation of C-reactive protein mRNA by reverse transcriptase-polymerase chain
      reaction and of C-reactive protein levels by enzyme-linked immunosorbent assay.
      Conversely, C-reactive protein also triggered a significant release of high
      mobility group box 1 in vascular smooth muscle cell culture medium as determined
      by immunoblot. CONCLUSIONS: Activated vascular smooth muscle cells are the source
      of high-mobility group box 1 in human advanced atherosclerotic lesions. High
      mobility group box 1 directly stimulates the production of both C-reactive
      protein and matrix metalloproteinase through receptor for advanced glycation end
      product. These findings provide new evidence that high-mobility group box 1
      produced by activated vascular smooth muscle cells may contribute to the
      progression and vulnerability of human atherosclerotic lesions toward rupture.

PMID- 17502243
TI  - Elevated expressions of osteopontin and tenascin C in ascending aortic aneurysms
      are associated with trileaflet aortic valves as compared with bicuspid aortic
      valves.
AB  - OBJECTIVE: Ascending aortic aneurysms (AscAAs) are a highly lethal condition
      whose pathobiology remains to be poorly understood. Although most AscAAs occur in
      the presence of a trileaflet aortic valve (TAV), a bicuspid aortic valve (BAV) is
      a common congenital anomaly associated with an increased risk for an AscAA and
      dissection independent of functional valve pathology but secondary to inherent
      structural abnormality of the aorta. The objective of this investigation was to
      compare the patterns of gene expression in aortas between TAV and BAV patients
      with the aim of identifying markers for AscAAs. METHODS: We used microarray
      analysis to first compare messenger RNA expressions between aneurysmal aortas
      from TAV patients (n=11) and those from BAV patients (n=11), identified genes
      overexpressed in TAV aneurysms, and compared expressions of the selected genes
      among TAV aneurysms, BAV aneurysms, and normal aortas (n=3). Finally, expressions
      of the selected genes were assessed by immunostaining of aortas from the TAV,
      BAV, and normal specimens. RESULTS: Two overexpressed genes in the TAV group,
      osteopontin (OPN) and tenascin C (TNC), were consistently more highly expressed
      in TAV aneurysms than in BAV aneurysms and normal aortas as determined by real
      time reverse transcriptase quantitative polymerase chain reaction and
      immunohistochemistry. Differential staining revealed that OPN protein was
      concentrated in the medial smooth muscle and that TNC protein was concentrated
      around the vasa vasorum. CONCLUSIONS: We identified two novel potential markers,
      OPN and TNC, that are strongly associated with TAV aneurysms. The roles of OPN
      and TNC in influencing extracellular matrix remodeling in AscAAs warrant further
      investigation.

PMID- 17502244
TI  - Comparison of coronary heart disease risk factors in autopsied young adults from
      the PDAY Study with living young adults from the CARDIA study.
AB  - BACKGROUND: Disease is sometimes best studied by examination of tissue obtained
      from autopsied individuals. Results derived from autopsied persons are considered
      biased because many factors influence the decision to perform an autopsy, and
      variables measured postmortem may be affected by changes immediately prior to
      death and emergency medical treatment. METHODS: The Pathobiological Determinants
      of Atherosclerosis in Youth (PDAY) study measured coronary heart disease risk
      factors postmortem in autopsied young adults 23-34 years of age dying from
      external causes (accidents, homicides, suicides). The Coronary Artery Risk
      Development in Young Adults (CARDIA) study measured risk factors in living
      subjects of similar ages. RESULTS: Within sex, race, and age groups, the
      differences in body mass index between PDAY and CARDIA were significant but
      small. The prevalences of hyperglycemia/diabetes within sex, race, and age groups
      were similar in PDAY and CARDIA; overall, blacks in PDAY, but not in CARDIA, had
      a higher prevalence than whites. Serum lipoprotein concentrations were slightly
      and significantly higher and significantly more variable in PDAY subjects than in
      CARDIA subjects; the greater variability was interpreted as due primarily to
      emergency medical treatment. Prevalences of smoking and hypertension were
      substantially higher in PDAY subjects. CONCLUSIONS: Although there were
      statistically significant differences, the overall similarity of the risk factors
      in the two studies supports the validity of investigating associations of risk
      factors measured postmortem with anatomically determined arterial lesions in
      autopsied young adults dying from external causes. The greater variability in
      postmortem serum measurements attenuates but does not obscure associations.

PMID- 17502245
TI  - Diminished zonula occludens-1 expression in the failing human heart.
AB  - BACKGROUND: Reduced expression of the major gap junction protein connexin 43
      (Cx43) in the failing human heart may lead to arrhythmias and sudden cardiac
      death. Cx43 interacts with the actin binding protein, zonula occludens-1 (ZO-1),
      and it has recently been demonstrated that ZO-1 regulates the formation and
      function of Cx43 gap junctions. We hypothesize that normal expression of ZO-1 and
      its interaction with Cx43 are required for appropriate assembly and function of
      Cx43 gap junctions in the heart. Here, we determined whether expression of ZO-1
      is altered in patients with heart failure. METHODS: We examined ventricular
      myocardium from hearts of patients in end-stage heart failure, obtained at
      transplant, for ZO-1 expression by immunohistochemistry. We also subjected
      lysates made from this tissue to immunoblotting to determine the level of ZO-1
      expression. RESULTS AND CONCLUSIONS: ZO-1 was found at 96% of the intercalated
      discs in nonfailing control human hearts, where it colocalized with Cx43. In
      contrast, there was ZO-1 immunostaining at 5% of intercalated discs in failing
      hearts, coincident with a reduction in Cx43 staining in intercalated discs.
      Immunoblotting analysis showed that there was a 95% reduction in ZO-1 expression
      in human heart failure. Loss of ZO-1 at intercalated discs in heart failure may
      play a critical role in remodeling of Cx43 gap junctions, which may contribute to
      abnormal impulse propagation and arrhythmogenesis, thereby predisposing patients
      in heart failure to sudden cardiac death.

PMID- 17502246
TI  - Percutaneous heart valve replacement: histology and calcification characteristics
      of biological valved stents in juvenile sheep.
AB  - INTRODUCTION: Percutaneous techniques to replace the pulmonary valve are emerging
      as an alternative to congenital cardiac surgical procedures. Promising
      experimental and early clinical results have been reported so far, focusing on
      technical feasibility and valved stent function. The present study aimed to
      describe the micropathology after experimental percutaneous valve replacement.
      METHODS: Self-expanding nitinol stents carrying a valved bovine jugular vein were
      transfemorally implanted into the pulmonary position of nine sheep. After 3
      months of survival, macro- and micropathological examinations were carried out
      using standard staining techniques and immunohistochemistry. Additionally,
      calcification characteristics were determined by X-ray examinations and von Kossa
      stainings. RESULTS: Six of nine animals survived the 3-month study time with good
      angiographic and echocardiographic function. All valves were grossly functional
      at the time of explantation. Slight fibrous overgrowth was seen at the inflow
      portions of two valved stents. No cuspal perforations or intracuspal hematomas
      were observed. Light microscopy proved the absence of cellular inflammatory
      infiltrates in any tissue samples. The myocardium directly proximal to the stent
      appeared structurally normal without calcification. The overall structure of the
      native pulmonary artery was well preserved with few mineral deposits spread
      diffusely throughout the wall distal to the stent. Massive calcification appeared
      in the bovine jugular-vein wall together with increased numbers of T lymphocytes.
      Neither calcific deposits in the cusps nor extrinsic mineralization was noted.
      CONCLUSION: For the first time, micropathologic evaluation of percutaneously
      implanted heart valves is described. The results demonstrate that calcification
      of valved stents occurs in the wall portions without affecting the cusps. The
      cardiac structures in the vicinity had normal histology without inflammation.

PMID- 17502247
TI  - Role of inflammation in nonrheumatic, regurgitant heart valve disease. A
      comparative, descriptive study regarding apolipoproteins and inflammatory cells
      in nonrheumatic heart valve disease.
AB  - BACKGROUND: Nonrheumatic aortic stenosis is the predominant cause of heart valve
      surgery in the Western world. Aortic and mitral regurgitation account for a
      lesser amount of the heart valve surgery. During the 1990s, inflammatory cell
      infiltrates have been demonstrated in nonrheumatic stenotic aortic valves. These
      findings suggest an inflammatory component in the pathogenesis of nonrheumatic
      aortic valve stenosis. However, nonrheumatic regurgitant aortic and mitral valves
      have not been investigated in this respect. The aim of this study was to compare
      nonrheumatic regurgitant aortic and mitral valves with stenotic aortic valves
      regarding the presence of T lymphocytes, macrophages, apolipoprotein B, and
      apolipoprotein A-I. METHODS: Valve specimens were obtained from 42 patients
      referred to hospital for surgery because of significant heart valve disease. From
      these patients, 29 aortic stenotic valves, 9 aortic regurgitant, and 6 mitral
      regurgitant valves, all nonrheumatic, were obtained for the study. Fourteen
      valves collected from subjects undergoing clinical/medicolegal autopsy were used
      as control. In order to identify mononuclear inflammatory cells and
      apolipoproteins, sections were investigated with immunohistochemical analyses and
      then categorized semiquantitatively. RESULTS: Regurgitant and control valves
      showed a significantly lower degree of inflammatory cell infiltrate and a lower
      degree of apolipoprotein deposition as compared to stenotic aortic valves.
      CONCLUSIONS: The signs of inflammation seen in nonrheumatic aortic stenosis are
      not prominent features in the nonrheumatic, regurgitant valves. This is
      consistent with the multi-factorial pathogenesis of these conditions.

PMID- 17502248
TI  - Biatrial primary cardiac paraganglioma: a rare finding.
AB  - The majority of primary cardiac tumors are benign; of these tumors, cardiac
      paragangliomas are among the rarest. We report a case of biatrial cardiac
      paraganglioma discovered during workup for palpitations and fatigue. The tumor
      involved the interatrial septum, with a lobulated portion protruding through the
      foramen ovale into the right atrium. The tumor was successfully excised, leading
      to uneventful recovery.

PMID- 17502249
TI  - Cardiac epithelioid hemangioendothelioma with 8-year follow-up.
AB  - An incidentally discovered right atrial mass excised from the heart of a 51-year
      old woman was found on pathological examination to be an epithelioid
      hemangioendothelioma. No further therapy was undertaken, and the patient has
      remained free of recurrence for 8 years. To our knowledge, this is the first
      report on the behavior of this distinctive vascular neoplasm occurring as an
      isolated cardiac tumor.

PMID- 17502250
TI  - Multiple synchronous atrial lipomas.
AB  - The incidence of primary tumors of the heart is low. Three quarters of cardiac
      neoplasms are benign. Cardiac lipomas are a mostly asymptomatic benign tumor that
      makes up less than 10% of primary heart tumors. There have been 60 reported cases
      of atrial lipomas and only two cases of multiple lesions. We present a case of
      multiple synchronous atrial lipomas causing obstruction of the tricuspid valve
      and partial occlusion of the coronary sinus requiring reconstruction.

PMID- 17502252
TI  - Objectively measuring and comparing performance levels of diagnostic imaging
      systems and practices.

PMID- 17502251
TI  - Mitral valve myxoma involving both leaflets.
AB  - Mitral valve myxomas are extremely uncommon, and their presence raises
      differential diagnosis with other pathologic conditions. We report on the case of
      a patient with an unspecific clinical presentation and an equivocal
      echocardiographic finding: mass prolapsing through the mitral valve into the left
      ventricle. The tumor was strongly attached by a wide pedicle, involving both the
      anterior and posterior mitral valve leaflets. Tumor excision was not feasible,
      and the mitral valve was replaced. Histologic analysis confirmed the myxomatous
      nature of the mass.

PMID- 17502253
TI  - Body diffusion-weighted MR imaging using high b-value for malignant tumor
      screening: usefulness and necessity of referring to T2-weighted images and
      creating fusion images.
AB  - RATIONALE AND OBJECTIVES: To evaluate the potential usefulness of high b-value
      body diffusion-weighted images (DWIs) as a screening tool in the depiction of
      abdominal malignant tumors. MATERIALS AND METHODS: We selected 110 abdominal
      magnetic resonance examinations (1.5 T; 60 men; age range, 25-90 years) with and
      without malignant tumors (n = 37 and n = 73, respectively). Axial DWIs were
      obtained by single-shot spin-echo (SE) type echo planar imaging (EPI) sequence
      with inversion pulse (repetition time, 6,800 msec; echo time, 100 msec; T1, 150
      msec; b value, 1,000 sec/mm(2)) without breath-holding. Two radiologists
      independently interpreted the DWIs, T2-weighted images (T2-WI), all three types
      of images including DWIs, T2-WIs, and fusion images at the same time (DWIs + T2
      WIs + fusion) with 7-14 days' interval, and the diagnostic confidence for each
      patient was scored. RESULTS: The area under the curve (AUC) of the composite
      receiver operating characteristic (ROC) curve of DWIs + T2-WIs + fusion (0.904)
      was significantly higher than those of DWIs (0.720; P < .001) and T2-WIs (0.822;
      P < .05). Both sensitivity and specificity were higher in DWIs + T2-WIs + fusion
      (89.5% and 81.9%, respectively) compared with those of DWIs (72.4% and 59.0%; P <
      .01 and P < .001, respectively). CONCLUSIONS: Abdominal high b-value DWIs have a
      high sensitivity and specificity for malignant tumors when T2-WIs are referred
      and image fusion technique is employed, suggesting that it may potentially be a
      new screening tool.

PMID- 17502254
TI  - Clinical evaluation of a computer-aided diagnosis (CAD) prototype for the
      detection of pulmonary embolism.
AB  - RATIONALE AND OBJECTIVES: To evaluate the performance of a prototype computer
      aided diagnosis (CAD) tool using artificial intelligence techniques for the
      detection of pulmonary embolism (PE) and the possible benefit for general
      radiologists. MATERIALS AND METHODS: Forty multidetector row computed tomography
      datasets (16/64- channel scanner) using 100 kVp, 100 mAs effective/slice, and 1
      mm axial reformats in a low-frequency reconstruction kernel were evaluated. A
      total of 80 mL iodinated contrast material was injected at a flow rate of 5
      mL/seconds. Primarily, six general radiologists marked any PE using a
      commercially available lung evaluation software with simultaneous, automatic
      processing by CAD in the background. An expert panel consisting of two chest
      radiologists analyzed all PE marks from the readers and CAD, also searching for
      additional finding primarily missed by both, forming the ground truth. RESULTS:
      The ground truth consisted of 212 emboli. Of these, 65 (31%) were centrally and
      147 (69%) were peripherally located. The readers detected 157/212 emboli (74%)
      leading to a sensitivity of 97% (63/65) for central and 70% (103/147) for
      peripheral emboli with 9 false-positive findings. CAD detected 168/212 emboli
      (79%), reaching a sensitivity of 74% for central (48/65) and 82%(120/147) for
      peripheral emboli. A total of 154 CAD candidates were considered as false
      positives, yielding an average of 3.85 false positives/case. CONCLUSIONS: The CAD
      software showed a sensitivity comparable to that of the general radiologists, but
      with more false positives. CAD detection of findings incremental to the
      radiologists suggests benefit when used as a second reader. Future versions of
      CAD have the potential to further increase clinical benefit by improving
      sensitivity and reducing false marks.

PMID- 17502256
TI  - Two-modality mammography may confer an advantage over either full-field digital
      mammography or screen-film mammography.
AB  - RATIONALE AND OBJECTIVES: We sought to compare the cancer detection rate and
      receiver operating characteristic (ROC) area under the curve of full-field
      digital mammography, screen-film mammography, and a combined technique that
      allowed diagnosis if a finding was suspicious on film mammography, on digital
      mammography, or both. MATERIALS AND METHODS: We used the data originally analyzed
      by Lewin and associates in 2002. In that trial, 6,736 paired full-field and
      digital mammograms were performed in 4,489 women. We used parametric and
      nonparametric tests to compare the area under the curve for ROC scores of film
      screen only, digital mammography only, and the combined test. We used McNemar's
      test for paired proportions to compare the cancer detection rates. RESULTS: With
      the parametric test, neither the difference in the area under the curve between
      the film and combined nor the difference between the digital and combined ROC
      curves was significant at the Bonferroni-corrected 0.025 alpha level (film versus
      combined difference = 0.0563, P = .0712; digital versus combined difference =
      0.0894, P = .0455). The nonparametric test showed that there was a significant
      difference between both film and combined (difference = 0.073, P = .008) and
      digital versus combined ROC curves (difference = 0.1164, P = .0008). The
      continuity-corrected McNemar's test showed a significant increase in the
      proportion of cancers detected by the combined modality over film (chi(2) =
      7.111, df = 1, P = .0077), and over digital (chi(2) = 12.071, df = 1, P = .0005).
      CONCLUSION: Using two mammograms, one film and one digital, significantly
      increases the detection of breast cancer.

PMID- 17502255
TI  - Computer-aided detection systems for breast masses: comparison of performances on
      full-field digital mammograms and digitized screen-film mammograms.
AB  - RATIONALE AND OBJECTIVES: To compare the performance of computer aided detection
      (CAD) systems on pairs of full-field digital mammogram (FFDM) and screen-film
      mammogram (SFM) obtained from the same patients. MATERIALS AND METHODS: Our CAD
      systems on both modalities have similar architectures that consist of five steps.
      For FFDMs, the input raw image is first log-transformed and enhanced by a
      multiresolution preprocessing scheme. For digitized SFMs, the input image is
      smoothed and subsampled to a pixel size of 100 microm x 100 microm. For both CAD
      systems, the mammogram after preprocessing undergoes a gradient field analysis
      followed by clustering-based region growing to identify suspicious breast
      structures. Each of these structures is refined in a local segmentation process.
      Morphologic and texture features are then extracted from each detected structure,
      and trained rule-based and linear discriminant analysis classifiers are used to
      differentiate masses from normal tissues. Two datasets, one with masses and the
      other without masses, were collected. The mass dataset contained 131 cases with
      131 biopsy proven masses, of which 27 were malignant and 104 benign. The true
      locations of the masses were identified by an experienced Mammography Quality
      Standards Act (MQSA) radiologist. The no-mass data set contained 98 cases. The
      time interval between the FFDM and the corresponding SFM was 0 to 118 days.
      RESULTS: Our CAD system achieved case-based sensitivities of 70%, 80%, and 90% at
      0.9, 1.5, and 2.6 false positive (FP) marks/image, respectively, on FFDMs, and
      the same sensitivities at 1.0, 1.4, and 2.6 FP marks/image, respectively, on
      SFMs. CONCLUSIONS: The difference in the performances of our FFDM and SFM CAD
      systems did not achieve statistical significance.

PMID- 17502257
TI  - Evaluation of 11-gauge and 9-gauge vacuum-assisted breast biopsy systems in a
      breast parenchymal model.
AB  - RATIONALE AND OBJECTIVES: To compare three commercially available vacuum-assisted
      breast biopsy systems for tissue yield, length and fragmentation of specimens.
      MATERIALS AND METHODS: Specimens were acquired from radiolucent (bacon) and
      radioopaque (turkey breast) tissue using three different commercially available
      vacuum-assisted breast biopsy devices. Two systems (system 1 and 2) were equipped
      with 11 G needles, one system (system 3) with a 9 G needle. As for systems 1 and
      2 a second chamber for applying the vacuum is attached to the needle, the
      external maximum diameter was identical for all three systems. 48 specimens were
      taken out for each tissue type and for each device. Specimens were measured for
      total weight, individual length, and number of fragments. Differences between
      groups were analyzed using analysis of variance (ANOVA) and Student's t-test.
      RESULTS: For both tissue types, system 1 and 2 showed similar results, for system
      3 tissue weight and length of specimens were larger. Differences in lengths and
      weight were statistically significant between system 1 and 3 and system 2 and 3
      (ANOVA, P < 0.05). Differences between length and weight were statistically
      significant between tissue 1 and 2 for all devices (t-Test < 0.05). CONCLUSION:
      As for system 3 a larger tissue yield was obtained with the same number of
      specimens compared to systems 1 and 2, it can be assumed that the same diagnostic
      accuracy as for systems 1 and 2 may be achieved for system 3 with less passes
      through tissue.

PMID- 17502258
TI  - Factors affecting decreasing radiation dose for mammography in North Carolina
      after 2002: an analysis of Food and Drug Administration annual surveys.
AB  - RATIONALE AND OBJECTIVES: We sought to determine which factors affected the
      decrease in average glandular dose recorded at the annual U.S. Food and Drug
      Administration Mammography Quality Standards Act inspections of mammography
      equipment in North Carolina from 2002 through 2005. MATERIALS AND METHODS:
      Average glandular dose, half-value layer, kVp, equipment age, processing speed,
      and system speed for every mammography unit in the state were collected by Food
      and Drug Administration-trained state inspectors. A mixed-effect model was used
      to evaluate the changes of glandular dose over time and to identify the factors
      associated with these changes. RESULTS: There was a statistically significant
      decrease in average glandular dose in North Carolina since 2002. Factors that
      were statistically significantly associated with this effect were changes in kVp,
      equipment age, processing speed, and system speed. CONCLUSION: Average glandular
      dose for mammography has decreased in North Carolina after 2002. This change is
      probably at least partially due to the cumulative effect of direct intervention
      by mammography consultants and statewide educational seminars on mammography
      quality control.

PMID- 17502259
TI  - Evidence of subcortical and cortical aging of the acoustic pathway: a diffusion
      tensor imaging (DTI) study.
AB  - RATIONALE AND OBJECTIVES: During aging, there is evidence of microstructural
      changes in certain cortical and subcortical brain regions. Diffusion tensor
      imaging (DTI) is used to study age related microstructural changes in the
      acoustic pathway. MATERIALS AND METHODS: Twenty healthy volunteers (mean age 28.5
      years) and 15 healthy volunteers (mean age 61.3 years) were examined using a 1.5
      T MR system with a high-resolution T1-weighted sequence and an integrated
      parallel imaging technique DTI Echo-planar-imaging (EPI) sequence. For
      reliability, 10 subjects underwent a second examination 2 days later. The
      fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were
      measured in six brain regions of the auditory pathway. RESULTS: We found no
      left/right asymmetry in the selected brain structures. There were no significant
      differences (P < .05) in the ADC and FA in the lateral lemniscus and medial
      geniculate body of young and elderly subjects. However, FA was significantly
      increased (P < .05) in the inferior colliculus and decreased in the auditory
      radiation, the superficial temporal gyrus, and the transverse temporal gyrus in
      the elder subjects than in the younger ones. There were no significant
      differences in anisotropy in subsequent examinations in the younger individuals.
      CONCLUSIONS: These findings suggest evidence of age-related changes in the
      acoustic pathway. These changes are associated with a decrease in anisotropy
      mainly in the cortical grey and white matter rather than in the subcortical
      regions. Our DTI measurements were reproducible.

PMID- 17502260
TI  - The value of dynamic MRI studies in parotid tumors.
AB  - RATIONALE AND OBJECTIVES: To evaluate the ability of dynamic contrast-enhanced
      magnetic resonance imaging (MRI) to differentiate several tumor entities of the
      parotid gland in a prospective clinical trial. MATERIALS AND METHODS: A total of
      112 patients with parotid tumors were examined with dynamic contrast-enhanced 1.5
      T MRI. Precontrast axial T1-weighted imaging was used to select five slices for
      the dynamic study. Subsequently, a T1-weighted FLASH sequence was used for the
      dynamic contrast study (0.2 ml Gd/kg x body weight). Contrast agent application
      and the FLASH sequence were started simultaneously. Ten acquisitions of 10
      seconds' scan time each were performed (total acquisition time 1:40 minutes).
      Signal intensity versus time (SIvT) curves was obtained for all tumors. After
      correlation of the categorized SIvT curves, these were compared with
      histopathology. Finally, all MRIs together with the tumor specific SIvT curves
      were re-read and correlated with histopathologic diagnosis. All reading sessions
      were done by three experienced radiologists. RESULTS: Four characteristic
      intensity-time curves were observed: pleomorphic adenoma showed a gradual
      increase in signal intensity, followed by a plateau phase on a low intensity
      level. Cysts showed a vacillating course at a low signal intensity level.
      Adenolymphomas as well as carcinomas showed a rapid increase in signal intensity
      followed by a plateau phase. Statistic significance was found for the time-to
      peak values for adenolymphomas and pleomorphic adenomas and for the maximum peak
      signal intensity values for carcinomas. Together with other morphologic MRI
      criteria (contrast enhancement, border characteristics) and clinical features, a
      differentiation between adenolymphoma and carcinoma was possible. CONCLUSIONS:
      With additional dynamic contrast-enhanced MRI, a more reliable differentiation
      between common parotid tumors is possible before surgery.

PMID- 17502261
TI  - Satisfaction of search in multitrauma patients: severity of detected fractures.
AB  - RATIONALE AND OBJECTIVES: Satisfaction of search (SOS) occurs when an abnormality
      is missed because another abnormality has been detected. This research studied
      whether the severity of a detected fracture determines whether subsequent
      fractures are overlooked. MATERIALS AND METHODS: Each of 70 simulated multitrauma
      patients presented examinations of three anatomic areas. Readers evaluated each
      patient under two experimental conditions: when the images of the first anatomic
      area included a fracture (the SOS condition), and when it did not (the control
      condition). The SOS effect was measured on detection accuracy for subtle test
      fractures presented on examinations of the second and third anatomic areas. In an
      experiment with 12 radiology readers, the initial SOS radiographs showed
      nondisplaced fractures of extremities, fractures associated with low morbidity.
      In another experiment with 12 different radiology readers, the initial
      examination, usually a computed tomography scan, showed cervical and pelvic
      fractures of the type associated with high morbidity. Because of their more
      direct role in patient care, the experiment using high morbidity SOS fractures
      was repeated with 17 orthopedic readers. RESULTS: Detection of subtle test
      fractures was substantially reduced when fractures of low morbidity were added (P
      < .01). No similar SOS effect was observed in either experiment in which added
      fractures were associated with high morbidity. CONCLUSIONS: The satisfaction of
      search effect in skeletal radiology was replicated, essentially doubling the
      evidence for SOS in musculoskeletal radiology, and providing an essential
      contrast to the absence of SOS from high-morbidity fractures.

PMID- 17502262
TI  - Assessment of medical imaging systems and computer aids: a tutorial review.
AB  - This article reviews the central issues that arise in the assessment of
      diagnostic imaging and computer-assist modalities. The paradigm of the receiver
      operating characteristic (ROC) curve--the dependence of the true-positive
      fraction versus the false-positive fraction as a function of the level of
      aggressiveness of the reader/radiologist toward a positive call--is essential to
      this field because diagnostic imaging systems are used in multiple settings,
      including controlled laboratory studies in which the prevalence of disease is
      different from that encountered in a study in the field. The basic equation of
      statistical decision theory is used to display how readers can vary their level
      of aggressiveness according to this diagnostic context. Most studies of
      diagnostic modalities in the last 15 years have demonstrated not only a range of
      levels of reader aggressiveness, but also a range of level of reader performance.
      These characteristics require a multivariate approach to ROC analysis that
      accounts for both the variation of case difficulty and the variation of reader
      skill in a study. The resulting paradigm is called the multiple-reader, multiple
      case ROC paradigm. Highlights of historic as well as contemporary work in this
      field are reviewed. Many practical issues related to study design and resulting
      statistical power are included, together with recent developments and
      availability of analytical software.

PMID- 17502263
TI  - A practical approach for inexpensive searches of radiology report databases.
AB  - RATIONALE AND OBJECTIVES: We present a method to perform full text searches of
      radiology reports for the large number of departments that do not have this
      ability as part of their radiology or hospital information system. MATERIALS AND
      METHODS: A tool written in Microsoft Access (front-end) has been designed to
      search a server (back-end) containing the indexed backup weekly copy of the full
      relational database extracted from a radiology information system (RIS). This
      front end-/back-end approach has been implemented in a large academic radiology
      department, and is used for teaching, research and administrative purposes.
      RESULTS: The weekly second backup of the 80 GB, 4 million record RIS database
      takes 2 hours. Further indexing of the exported radiology reports takes 6 hours.
      Individual searches of the indexed database typically take less than 1 minute on
      the indexed database and 30-60 minutes on the nonindexed database. Guidelines to
      properly address privacy and institutional review board issues are closely
      followed by all users. CONCLUSIONS: This method has potential to improve
      teaching, research, and administrative programs within radiology departments that
      cannot afford more expensive technology.

PMID- 17502264
TI  - A web-based interface for communication of data between the clinical and research
      environments without revealing identifying information.
AB  - RATIONALE AND OBJECTIVES: Recent health care policies and regulations have
      affected the manner in which patient data--especially protected health
      information (PHI)--are handled in both the clinical and research settings.
      Specifically, it is now more challenging to obtain de-identified PHI from the
      clinic for use in research while adhering to the requirements of this new
      environment. MATERIALS AND METHODS: To meet this challenge, we have devised a
      novel web-based interface that facilitates the communication of data (eg, biopsy
      results) between the clinic and research environments without revealing PHI to
      the research team or associated research identifiers to the clinical
      collaborators. At the heart of the scheme is a web application that coordinates
      message passing between the researchers (in general, the requesters of de
      identified PHI) and clinical collaborators (who have access to PHI) by use of a
      protocol that protects confidentiality. RESULTS: We describe the design
      requirements of this communication scheme and present implementation details of
      the web application and its associated database. CONCLUSIONS: We conclude that
      this scheme provides a useful communication mechanism that facilitates clinical
      research while maintaining confidentiality of patient data.

PMID- 17502265
TI  - The high cost of all sorts of things.

PMID- 17502266
TI  - Carpets and books.

PMID- 17502267
TI  - Structural characterization of natural rubber based on recent evidence from
      selective enzymatic treatments.
AB  - A structural characterization of natural rubber (NR) was carried out by a
      combination of selective enzymatic treatment and high-resolution characterization
      techniques. The nitrogenous groups in NR from Hevea brasiliensis have been
      regarded as an important factor governing cured rubber properties, although there
      is no structural evidence to prove that relationship. The nitrogenous compounds
      in highly purified NR were characterized to determine the origin of the
      nitrogenous groups in NR. The rubber particles of fresh latex were purified by
      washing, i.e., a successive dilution of the cream fraction and concentration by
      centrifugation in the presence of a surfactant. The nitrogen content of the NR
      formed from the washed rubber particles decreased from 0.281% to 0.015% after
      washing 3-5 times; this content was similar to that of NR deproteinized by a
      proteolytic enzyme. The presence of 1-2 nitrogen atoms per rubber chain was
      estimated on the basis of nitrogen content and number-average molecular weight
      (Mn). The nitrogen content of fractionated rubber fractions from rubber particles
      washed for five times increased with increasing Mn. The nitrogenous groups in
      rubber chains are postulated to mostly originate from phospholipids associating
      with branch points and functional groups formed by oxidation and successive
      reactions in NR latex. An analysis of the structure of the chain end group (alpha
      terminal) was carried out by treating the deproteinized NR (DPNR) latex with
      lipase, phosphatase, and phospholipases A(2), B, C and D. The enzymatic treatment
      of DPNR latex significantly decreased the long-chain fatty acid ester content in
      DPNR, and also the Mn and Higgins'k' constant, except for phospholipase D
      treatment. This indicates the presence of phospholipid molecules in NR, which
      connect rubber molecules together. (1)H-NMR results of rubber obtained from DPNR
      latex showed weak signals due to monophosphate, diphosphate and phospholipids at
      the alpha-terminal. Treating DPNR latex with lipase and phosphatase decreased the
      relative intensity of the (1)H-NMR signals corresponding to phospholipids;
      however, with the same treatment, no change in the signals due to mono- and
      diphosphates was observed. The presence of mono- and diphosphates as well as some
      phospholipid signals after lipase and phosphatase treatment indicates that mono-
      and diphosphate groups are directly linked to the modified structure at their
      alpha-terminals; such connections are considered to be due to the association or
      linkage of such groups with phospholipid.

PMID- 17502268
TI  - Functional characterization and evolutionary implication of the internal 157
      amino-acid sequence of an exoinulinase from Penicillium sp. strain TN-88.
AB  - An extracellular exoinulinase from the filamentous fungus Penicillium sp. strain
      TN-88 has a 14-fold higher specific activity of 743 U/mg toward inulin than its
      equivalent from the Aspergillus niger strain 12 and possesses an internal 157
      amino-acid sequence whose corresponding region is absent in the A. niger enzyme.
      On the basis of sequence alignment, the internal region D' encoding the 157-amino
      acid sequence in the Penicillium exoinulinase gene inuD cDNA was inserted into
      the site between the nucleotides 897 and 898 of the A. niger exoinulinase gene
      inuE cDNA. The resultant inuE::D' fusion was expressed in the methylotrophic
      yeast Pichia pastoris. The K(m) value of the secreted hybrid enzyme InuE::D' for
      inulin hydrolysis was about 1/15 that of the A. niger InuE, whereas its k(cat)
      value did not differ greatly from that of the InuE. These observations indicate
      that the Penicillium exoinulinase has evolved by the horizontal transfer and
      integration of a relevant DNA segment and that the internal sequence D' functions
      as an additional noncatalytic inulin-affinity region.

PMID- 17502269
TI  - Electrically induced protein release from Schizosaccharomyces pombe cells in a
      hyperosmotic condition during and following a high electropulsation.
AB  - A high-electric-field application of fission yeast cells under hyperosmotic
      conditions improved the electro-induced release of protein and cytoplasmic
      enzymes. A cell suspension was pulsed at 12.5 kV/cm for 10 ms in a batch system
      and immediately postincubated at 30 degrees C. The total protein release rate
      from cells increased in the hypertonic solutions of 1.5-2.5 M sorbitol to
      approximately threefold higher than those in the hypotonic and isotonic solutions
      of 0-0.5 M sorbitol. The protein release rate in 2.0 M sorbitol greatly increased
      up to 4.5 h and then gradually increased after 7.5 h. The maximum activities of
      cytoplasmic enzymes, such as alcohol dehydrogenase and 3-phosphoglycerate kinase,
      were obtained at 7.5 h after electropulsation in 2.0 M sorbitol, yielding
      approximately 90% of the enzyme activity levels found in spheroplast lysate. On
      the other hand, the release rates of protease in vacuoles and invertase in
      periplasmic space did not depend on osmotic solutions during electric pulse
      application.

PMID- 17502270
TI  - Association study between Apolipoprotein L and schizophrenia by exhaustive and
      rule-based combination analysis for identification of multilocus interactions.
AB  - Several single marker association and haplotypic analyses have been performed to
      identify susceptible genes for various common diseases, but these approaches
      using candidate genes did not provide accurate and consistent evidence in each
      analysis. This inconsistency is partly due to the fact that the common diseases
      are caused by complex interactions among various genetic factors. Therefore, in
      this study, to evaluate exhaustive genotype or allele combinations, we applied
      the binomial and random permutation test (BRP) proposed by Tomita et al. [IPSJ
      Digital Courier, 2, 691-709 (2006)] for the association analysis between an
      Apolipoprotein L gene cluster and schizophrenia. Using the seven selected
      representative single nucleotide polymorphisms (SNPs) based on the results of
      linkage disequilibrium evaluation, we analyzed 845 schizophrenic patients and 707
      healthy controls, and investigated the validation of risk and protective factors
      with two randomly divided data sets. A comparative study of a method for
      analyzing the interactions was performed by conventional methods. Even if all the
      tested methods were used for analysis, the risk factor with a high significance
      was not commonly selected from both independent data sets. However, the
      significant interactions for the protective factor against disease development
      were commonly obtained from both data sets by BRP analysis. In conclusion,
      although it is considered that the causality of schizophrenia is too complex to
      identify a susceptible interaction using a small sample size, it was suggested
      that the healthy controls tend to have the same combination of certain alleles or
      genotypes for protection from disease development when BRP as a new exhaustive
      combination analytical method was used.

PMID- 17502271
TI  - Acetylation of loofa (Luffa cylindrica) sponge as immobilization carrier for
      bioprocesses involving cellulase.
AB  - The feasibility of using loofa sponge for immobilization of cellulase-producing
      microorganisms was investigated by acetylating loofa sponge. Acetylation was
      achieved by autoclaving process of loofa sponge immersed in acetic anhydride at
      various temperatures for various times. The degree of acetylation, as inferred by
      the weight percentage gain (WPG), was enhanced by increasing both temperature and
      the duration of acetylation. The acetylation of a piece of loofa sponge in an
      autoclave at 120 degrees C for 20 min resulted in a WPG of about 8%, which was
      sufficient to protect the loofa sponge against cellulose degradation. The
      acetylated loofa sponge prepared under this condition was not decomposed by
      commercial cellulase and its structure was maintained for more than 720 h during
      repeated-batch treatments with commercial cellulase. A flocculating yeast
      (Saccharomyces cerevisiae IR-2) and a fungus (Trichoderma reesei QM9414) were
      successfully immobilized in the acetylated loofa sponge. In each case, the
      percentage of immobilized cells was as high as that obtained using nonacetylated
      loofa sponge. Acetylation had no adverse effects on cell growth and
      immobilization of T. reesei QM9414, as well as on cell growth and ethanol
      production by S. cerevisiae IR-2. T. reesei QM9414 immobilized on an acetylated
      loofa sponge was successfully used for repeated-batch cellulase production from
      commercial cellulose powder. Although the acetylated loofa sponge showed a slight
      weight loss, it was not disintegrated by activated sludge. The results obtained
      in this study showed that acetylated loofa sponge is suitable as an
      immobilization carrier for bioprocesses involving cellulase.

PMID- 17502272
TI  - Development of stable flocculent Saccharomyces cerevisiae strain for continuous
      Aspergillus niger beta-galactosidase production.
AB  - A flocculent Saccharomyces cerevisiae strain was engineered to stably secrete
      Aspergillus niger beta-galactosidase in a continuous high-cell-density
      bioreactor. The delta-sequences from the yeast retrotransposon Ty1 were used as
      target sites for the integration of the beta-galactosidase expression cassette.
      High-copy-number transformants were successfully obtained using the delta
      integration system together with the dominant selection antibiotic, G418. The
      integration of multiple copies was confirmed by genomic Southern blot analysis.
      Integrants with the highest beta-galactosidase levels (approximately eight gene
      copies) had similar beta-galactosidase activities as a recombinant strain
      carrying the beta-galactosidase expression cassette in a YEp-based vector. The
      beta-galactosidase expression cassettes integrated into the yeast genome were
      stably maintained after eight sequential batch cultures in a nonselective medium.
      In continuous high-cell-density culture under the same operating conditions, the
      integrant strain was more stable than the plasmid-carrying strain. To our
      knowledge, this is the first study of multicopy delta-integrant stability in a
      continuous bioreactor operating at different dilution rates.

PMID- 17502273
TI  - Isolation and characterization of a lipid-degrading bacterium and its application
      to lipid-containing wastewater treatment.
AB  - To construct an efficient lipid-containing wastewater treatment system,
      microorganisms that degrade lipids efficiently were isolated from various
      environmental sources. Strain DW2-1 showed the highest rate of degradation of 1%
      (w/v) salad oil among the isolated strains. Strain DW2-1 was identified as
      Burkholderia sp. and designated Burkholderia sp. DW2-1. The rate of degradation
      of salad oil, olive oil, sesame oil, and beef tallow by strain DW2-1 were 96.7%,
      92.3%, 90.1% and 77.4%, respectively, during a 48-h cultivation. Strain DW2-1
      grew well in a synthetic wastewater medium (>1 x 10(10) colony forming unit
      [CFU]/ml) between 20 degrees C and 38 degrees C, and its rate of degradation of
      salad oil was above 90% after a 48-h cultivation. The lipase and biosurfactant
      (BSF) activities of strain DW2-1 after a 48-h cultivation were 1720 U/l and 480
      U/ml, respectively. In continuous cultures for lipid-containing wastewater
      treatment, DW2-1 was stably maintained and degraded more than 90% of salad oil
      during a 7-d cultivation.

PMID- 17502274
TI  - Optimization of bioprocess for production of copper-enriched biomass of
      industrially important microorganism Saccharomyces cerevisiae.
AB  - The production of Saccharomyces cerevisiae cells enriched with copper and the
      effects of adding copper ions to different media on yeast cell growth and ethanol
      production were studied. In the media Cu(2+) concentrations of up to 0.094 mM had
      no effect on alcoholic fermentation, whereas higher Cu(2+) concentrations
      markedly decreased yeast cell growth rate and ethanol production. Under static
      conditions, the maximum amounts of copper uptake (i.e., 1.16 mg/g, 1.2 mg/g and
      0.81 mg/g dry matter yeast biomass for glucose, sucrose and molasses media,
      respectively) were obtained after 8 h of fermentation, whereas under dynamic
      conditions smaller amounts of copper uptake (i.e., 0.98 mg/g, 1.02 mg/g and 0.7
      mg/g dry matter yeast biomass for glucose, sucrose and molasses media,
      respectively) were obtained after 6 h of fermentation.

PMID- 17502275
TI  - Relationship between solid retention time and phosphorus removal in anaerobic
      intermittent aeration process.
AB  - Solid retention time (SRT) is one of the most important control parameters in
      biological phosphorus removal. In this study, lab-scale biological nutrient
      removal (BNR) reactors using anaerobic-intermittent aeration (AIA) were operated
      at various SRTs (i.e., 15, 20, and 30 d) to evaluate their phosphorus removal
      efficiencies. Sludge wasting load decreased as SRT increased; however, the
      phosphorus content in the biomass increased as SRT increased. The highest
      phosphorus removal efficiency was 93% at an SRT of 20 d and the phosphorus
      wasting load was also highest at that SRT, which indicates that the optimal SRT
      for the highest phosphorus removal is not proportional to the phosphorus content
      in the biomass. Aerobic digestion experiments were also carried out to determine
      the number of phosphate-accumulating organisms (PAOs) in the biomass produced in
      different reactors. All three activated sludges from BNR at SRTs of 15, 20, and
      30 d showed a slower volatile suspended solid (VSS) destruction rate and a larger
      amount of phosphorus released than the conventional activated sludge (CAS),
      suggesting that the activated sludge from BNR has more PAOs than CAS. Also, the
      sludge at an SRT of 30 d showed a slower VSS destruction rate and a larger amount
      of phosphorus released than the sludge at an SRT of 15 d, suggesting that PAOs
      are more predominant at longer SRTs. Thus, to improve phosphorus removal
      efficiency, it is recommended that SRT be increased to maximize the number of
      PAOs in the system and that SRT be determined to maximize phosphorus wasting
      load.

PMID- 17502276
TI  - Lyophilization of lipase with cyclodextrins for efficient catalysis in ionic
      liquids.
AB  - Lipase was lyophilized with cyclodextrins to prepare lipase formulation suitable
      for the efficient resolution of allethrolone in ionic liquids. The effects of the
      type and amount of cyclodextrin used on lipase preparation were evaluated, and
      the properties of lyophilized lipase such as thermostability and pH sensitivity
      were investigated and compared with those of native lipase. The results showed
      that lipase lyophilized with cyclodextrins can achieve a higher conversion rate
      than the native one, and that lipase lyophilized with inorganic salts cannot
      improve the conversion rate of the resolution reaction. The catalytic behavior of
      the lyophilized lipase was strongly dependent on cyclodextrin type and reaction
      media. The activity of the lyophilized lipase increased as the amount of added
      cyclodextrins increased. The activity of the lipase lyophilized with
      cyclodextrins was optimum at pH 7 and 40 degrees C, which was similar to that of
      the native one, but the half-life of the lyophilized lipase was low compared with
      that of the native one.

PMID- 17502277
TI  - Microaeration enhances productivity of bioethanol from hydrolysate of waste house
      wood using ethanologenic Escherichia coli KO11.
AB  - This is the first study showing the successful application of waste house wood
      (WHW) to the pilot-scale production of bioethanol by hydrolysis using diluted
      acid and fermentation using the ethanologenic recombinant Escherichia coli KO11.
      The major sugars in the WHW hydrolysate were glucose, mannose and xylose; the
      percentages were approximately 35%, 35% and 20% (w/w), respectively. In anaerobic
      fermentation using a 5-l reactor in which the oxygen transfer rate (OTR) was 0
      mmol/(l x h), KO11 consumed only 25% of the xylose in the WHW hydrolysate over
      the examined fermentation time of 100 h; however, hexoses such as glucose and
      mannose were consumed completely. Microaeration at an OTR of 4 mmol/(l x h)
      enhanced the xylose utilization ratio of KO11 to 100%, at which the ethanol
      concentration was 35.4 g/l and the ethanol yield was 0.42, although the maximum
      ethanol concentrations were 28.8 and 26.6 g/l at OTRs of 0 mmol/(l x h) and 15
      mmol/(l x h), respectively. Moreover, this microaerobic fermentation at OTR of 4
      mmol/(l x h) was applied to 1000-l scale bioethanol production using the WHW
      hydrolysate. The xylose utilization ratio reached 100% and the ethanol yield was
      determined to be 0.45 for a 63-h fermentation, which were comparable to those
      obtained from the laboratory-scale fermentation.

PMID- 17502278
TI  - Development of novel method for screening microorganisms using symbiotic
      association between insect (Coptotermes formosanus Shiraki) and intestinal
      microorganisms.
AB  - It is becoming increasingly difficult to isolate novel useful microorganisms from
      the natural environment using conventional screening methods based on pure
      culture techniques. A novel method for screening microorganisms in symbiotic
      association with insects was developed. This method involves the following two
      steps. In the first step, the existence of desired microorganisms that grow well
      by degrading difficult-to-degrade materials in the gut of insects is detected
      using the survivability of insects as an indicator. In the second step, the
      desired microorganisms are selected from the surviving insects. The second step
      is based on an idea that the guts of insects act as continuous-culture systems
      whereby microorganisms that cannot degrade diet components are washed out whereas
      those that can degrade diet components are retained and made to multiply in the
      gut. Coptotermes formosanus Shiraki was fed with an artificial diet containing
      phenol as a model of lignin-derived and difficult-to-degrade compound. Each C.
      formosanus feeding on an artificial diet containing 100 mg/l phenol had different
      levels of adaptation to the toxicity of phenol. About 20% of C. formosanus fed
      with an artificial diet containing 100 mg/l phenol died within a few days whereas
      others survived for more than 10 d. The structure of the intestinal
      microorganisms of the surviving C. formosanus fed with the 100 mg/l phenol
      artificial diet gradually changed and was very different from that of the
      bacterial communities obtained from the enrichment culture of wood-feeding C.
      formosanus using an artificial medium containing phenol as a sole carbon source.
      Furthermore, Only three species (as DGGE band) were detected from the gut of wood
      feeding C. formosanus, whereas 200 times more phenol-degrading microorganisms
      were detected in the gut of C. formosanus feeding on a phenol artificial diet.
      Out of these nine species (as DGGE band) of phenol-degrading microorganisms were
      isolated. The screening method developed in this study can also be applied to
      various insects, leading to the isolation of various microorganisms that can
      degrade difficult-to-degrade compounds.

PMID- 17502279
TI  - Production of butyl acetate ester by lipase from novel strain of Rhizopus oryzae.
AB  - A new lipase preparation from Rhizopus oryzae was used to catalyze the
      esterification reaction between acetic acid and butanol to produce butyl acetate
      ester (pineapple flavor). This flavor compound can be used in food, cosmetic and
      pharmaceutical industries. Only 3% of butyl acetate was obtained when free lipase
      was used in the synthesis containing only the substrates. In contrast, the
      conversion yield reached 25% when immobilized lipase was used under the same
      conditions. The synthesis of butyl acetate catalyzed by immobilized lipase in
      nonconventional media was optimized. A maximum conversion yield of 60% in a
      solvent-free system was obtained under the following conditions: amount of
      immobilized lipase, 500 IU; amount of initially added water, 45%; acetic
      acid/butanol molar ratio, 1:1; and in incubation temperature, 37 degrees C.
      Immobilized lipase could be repeatedly used for three cycles without a decrease
      in synthesis activity. The production of butyl acetate esters by immobilized R.
      oryzae lipase was also studied in the presence of organic solvents. Compared with
      a solvent-free system, the synthesis activity was improved in the presence of
      heptane and hexane with conversion yields of 80% and 76%, respectively. However,
      solvent-free systems tend to purify more easily the products without any toxicity
      and inflammability problems.

PMID- 17502280
TI  - Evidence for an additional disulfide reduction pathway in Escherichia coli.
AB  - An Escherichia coli cell-free protein synthesis cell extract has been created
      that lacks all known cytoplasmic disulfide reduction pathways but still retains
      significant reductase activity. Oxidized glutathione was partially stabilized by
      deleting the gene for glutathione reductase. To avoid previously reported AhpC
      mutations, thioredoxin reductase was only removed after extract preparation. The
      trxB gene was extended to encode a hemagglutinin tag so that TrxB could be
      removed by affinity adsorption. However, significant glutathione reductase
      activity remained. The unknown glutathione reductase pathway is disabled by
      iodoacetamide, is inhibited by NADH, and appears to use NADPH as an electron
      source.

PMID- 17502281
TI  - Construction and analysis of self-cloning sake yeasts that accumulate proline.
AB  - We constructed self-cloning diploid sake yeast strains that accumulate proline.
      The appropriate proline level is important for its protective effect against
      ethanol stress in yeast cells. Sake brewed with the proline-accumulating strains
      contained two- to threefold more proline than the sake brewed with the parent
      strain. It was also suggested that intracellular proline does not affect overall
      fermentation profiles, but reduces fermentation time in terms of ethanol
      production rate.

PMID- 17502282
TI  - Flexibility and strictness in functional replacement of domain III of cry
      insecticidal proteins from Bacillus thuringiensis.
AB  - Cry1C, one of the lepidopteran-specific insecticidal proteins from Bacillus
      thuringiensis, exhibits potent cytotoxicity against Sf9, an insect cell line.
      Cry1Aa and Cry4A, which are lepidopteran- and dipteran-specific insecticidal
      proteins, respectively, show no cytotoxicity against Sf9. When domain III of
      Cry1C was replaced with that of Cry1Aa or Cry4A, the hybrid Cry1C protein
      retained the cytotoxicity. These results suggest that domain III of Cry1C is not
      crucial in determining the cytocidal specificity of Cry1C against Sf9.

PMID- 17502283
TI  - Image cytometry for analyzing regional distribution of cells inside human
      neurospheres.
AB  - An image cytometry algorithm was developed to identify and quantify
      immunologically labeled cells in cultured human neurospheres. Image cytometry
      revealed new findings in terms of the localization of specific types of neural
      cells and the regional fluctuation of cell density in neurospheres. The
      distributions of total cell density exhibited similar profiles along the radial
      distance from the periphery of a neurosphere, irrespective of neurosphere sizes
      examined; approximately 1.0 x 10(6) cell/mm(3) in the vicinity of the periphery
      and 6.0 x 10(5) cell/mm(3) in an inner region of 50-180 microm. In addition, BrdU
      positive (proliferating) cells were present at ratios of 53-64% across the entire
      region of the neurospheres, whereas BrdU-negative and beta III tubulin-positive
      cells (postmitotic neurons) were minorities in the neurospheres.

PMID- 17502284
TI  - [Epidemiology: a developing science].
AB  - The story of French epidemiology dates back to Daniel Bernoulli (1760), with
      regard to mathematical epidemiology,and to Pierre-Charles Louis (1838), with
      regard to 'numerical medicine', the ancestor of the modern evidence-based
      medicine. This thematic issue samples some of the recent issues of modern
      epidemiology: biostatisticians have developed a series of specialized techniques
      to encover the risk factors and to measure the proportion of the disease
      frequency they can account for (one paper). Epidemiology of chronic diseases is
      now providing new insights into the tricky relationships between environmental,
      genetic factors, and diseases (four papers). Epidemiology is not just concerned
      with diseases. All aspects of human biology and physiology for which a population
      approach is necessary, are concerned: one paper deals with the case of fecundity
      and fertility, which are studied by both demographic and epidemiological
      approaches. One of the roles of epidemiology is to bring rational answers to
      disputed issues in public health, such as the hazards of postmenopausal hormonal
      therapy (one paper). Finally, the power of mathematics is increasingly used to
      understand better the dynamics of infectious diseases (two papers).

PMID- 17502285
TI  - Biostatistics and epidemiology: measuring the risk attributable to an
      environmental or genetic factor.
AB  - Disease frequency is measured through estimating incidence rates or disease risk.
      Several measures are used for assessing exposure-disease association, with
      adjusted estimates based on standardization, stratification, or more flexible
      regression techniques. Several measures are available to assess an exposure
      impact in terms of disease occurrence at the population level, including the
      commonly used attributable risk (AR). Adjusted AR estimation relies on
      stratification or regression techniques. Sequential and partial ARs have been
      proposed to handle the situation of multiple exposures and circumvent the
      associated non-additivity problem. Despite remaining issues in properly
      interpreting AR, AR remains a useful guide to assess prevention strategies.

PMID- 17502286
TI  - Coronary heart disease aetiology: associations and causality.
AB  - Coronary heart disease (CHD) prevention has largely benefited in the past from
      the development of epidemiological research. However, the opposition association
      causation is currently raised from observational data. We successively review,
      from some important examples, the classical methodological approach for
      discussing causality in epidemiology. The easy identification of DNA
      polymorphisms has prompted new CHD aetiological research in the past 10 years.
      Causality of the associations presents some special characteristics when genes
      are involved: necessity of replication, Mendelian randomization..., which might
      prove to be important in future research.

PMID- 17502287
TI  - Progress in the epidemiological understanding of gene-environment interactions in
      major diseases: cancer.
AB  - Cancer epidemiology has undergone marked development since the 1950s. One of the
      most spectacular and specific contributions was the demonstration of the massive
      effect of smoking on the occurrence of lung, larynx, and bladder cancer. Major
      chemical, physical, and biological carcinogenic agents have been identified in
      the working environment and in the overall environment. The chain of events from
      environmental exposures to cancer requires hundreds of polymorphic genes coding
      for proteins involved in the transport and metabolism of xenobiotics, or in
      repair, or in an immune or inflammatory response. The multifactorial and
      multistage characteristics of cancer create the theoretical conditions for
      statistical interactions that have been exceptionally detected. Over the last two
      decades, a considerable mass of data has been generated, mostly addressing the
      interactions between smoking and xenobiotic-metabolizing enzymes in smoking
      related cancers. They were sometimes considered disappointing, but they actually
      brought a lot of information and raised many methodological issues. In parallel,
      the number of polymorphisms that can be considered candidate per function
      increased so much that multiple testing has become a major issue, and genome wide
      screening approaches have more and more gained in interest. Facing the resulting
      complexity, some instruments are being set up: our studies are now equipped with
      carefully sampled biological collections, high-throughput genotyping systems are
      becoming available, work on statistical methodologies is ongoing, bioinformatics
      databases are growing larger and access to them is becoming simpler;
      international consortiums are being organized. The roles of environmental and
      genetic factors are being jointly elucidated. The basic rules of epidemiology,
      which are demanding with respect to sampling, with respect to the histological
      and molecular criteria for cancer classification, with respect to the evaluation
      of environmental exposures, their timeframes, quantification and covariables,
      with respect to study size and with respect to the rigor of multivariate
      analyses, are more pertinent than ever before.

PMID- 17502288
TI  - Interaction between genes and environment in neurodegenerative diseases.
AB  - Alzheimer's disease (AD) and Parkinson's disease (PD) are highly prevalent
      disorders that account for a large part of the global burden of neurodegenerative
      diseases. Most AD and PD cases occur sporadically and it is generally agreed that
      they could arise through interactions among genetic and environmental factors.
      Candidate genes involved in the metabolism of xenobiotics, neurodegeneration and
      functioning of dopaminergic neurons were found to be associated with PD. Some of
      these genes interact with environmental factors that could modify PD risk. Thus,
      we found that the inverse association between smoking and the risk of PD depended
      on a polymorphism of the iNOS (inducible NO synthase) gene. We also found that
      the cytochrome P450 2D6 gene could have a modifying effect on the risk of PD
      among persons exposed to pesticides. Both interactions have biological
      plausibility supported by laboratory studies and could contribute to better
      understand the aetiology of PD. A single susceptibility gene has been identified
      in sporadic AD. The epsilon4 allele of epsilon polymorphism of the apolipoprotein
      E gene (APOE) is strongly associated with AD, the risk of AD being multiplied by
      5 in persons carrying two epsilon4 alleles. The mechanism of the association
      between APOE and AD is poorly understood. A few interactions between the epsilon
      polymorphism and possible risk factors for AD have been described. However, these
      interactions had no biological plausibility and were likely due to chance.

PMID- 17502289
TI  - Gene-environment interactions in addictive disorders: epidemiological and
      methodological aspects.
AB  - The gene-environment interactions' approach could explain some epidemiological
      and clinical factors associated with addictive behaviours. Twin studies first
      help to disentangle the respective roles of environment and genetic effects,
      finding convincing evidence for common genetic vulnerability in several addictive
      behaviours, and helping to delimit what syndrome could belong to the addictive
      disorder spectrum. Assessing gene x environment interaction (G x E) needs
      specifically designed studies, using multiplicative or additive approaches.
      Focusing on this G x E interaction already showed its relevancy in many recent
      studies, using both epidemiological and molecular approaches. For example, in a
      non-human primate model of alcohol dependence assessing the respective role of
      genetic vulnerability (having the short allele located in the promoter region of
      the gene coding for the serotonin transporter) and severe fostering conditions
      (as locked up in a cage with other inmates for the first six months of life), the
      only group of monkeys that has a significant risk of using spontaneously alcohol
      is the one that gathers both risk factors, i.e. being peer-raised and having the
      short allele. Such approach could help to more accurately select specific
      candidate genes, to identify more homogenous subgroups of patients (as sharing
      the same genetic vulnerability), to understand how genetic factors mediate the
      risk of associated psychiatric disorders, and ultimately, may lead to more
      focused, i.e. more efficient, prevention strategies.

PMID- 17502290
TI  - Studies of fertility and fecundity: comparative approaches from demography and
      epidemiology.
AB  - The approaches used by demographers and by epidemiologists for studying the
      fecundity of couples (i.e. their ability to conceive) have converged, whereas
      they were historically divergent. Demography traditionally focused on fertility -
      the circumstances in which livebirths occur - with the aim of predicting
      population changes, in particular. Demographers also rapidly became interested in
      fecundity, developing concepts such as fecundability and definitive sterility.
      The measurement of fecundability is based on determination of the time to
      pregnancy (TTP), the basic tool of the epidemiologist. However, while
      demographers were developing methods for estimating the distribution of
      fecundability among couples based on TTP, epidemiologists turned to methods for
      analysing the role of diverse factors potentially influencing fecundity at the
      individual level.

PMID- 17502292
TI  - The perpetuation and epidemic recurrence of communicable diseases in human
      populations.
AB  - Recurrence of communicable diseases is a looming threat for human populations.
      Factors explaining the recurrences are partially known, involving demographics,
      biology, and complex relationships with the environment, but no comprehensive
      theory exists today. Here, we review some recent results obtained in modelling
      studies with a view to understanding better the mechanisms of perpetuation.
      Factors intrinsic to the interaction of pathogen and host have regained interest
      in this respect, especially with multiple pathogen and multiple population
      interactions. Extrinsic factors, including pure demography and environmental
      forcing are also strong predictors. With increasingly detailed data available,
      large-scale integrated models will help sorting out the multiple influences on
      recurrence.

PMID- 17502291
TI  - Observation versus intervention in the evaluation of drugs: the story of hormone
      replacement therapy.
AB  - Hormone replacement therapy, which was approved for menopausal symptoms, offers
      an opportunity to compare clinical trials and observational studies when
      evaluating the risks and benefits of drugs. The differences between randomized
      and observational evidence relate mainly to the risks of coronary heart diseases
      and dementia, higher or not elevated in users in trials, and decreased in
      observational studies. The most likely explanation for these discrepancies is bad
      accounting for confounders, in particular, time-dependent confounders in
      classical multivariate analyses and use of prevalent user design. Marginal
      structural models and new user design should help to diminish strongly indication
      bias in future observational studies aiming at the evaluation of the risks and
      benefits of drugs.

PMID- 17502293
TI  - Epidemic modeling in complex realities.
AB  - In our global world, the increasing complexity of social relations and transport
      infrastructures are key factors in the spread of epidemics. In recent years, the
      increasing availability of computer power has enabled both to obtain reliable
      data allowing one to quantify the complexity of the networks on which epidemics
      may propagate and to envision computational tools able to tackle the analysis of
      such propagation phenomena. These advances have put in evidence the limits of
      homogeneous assumptions and simple spatial diffusion approaches, and stimulated
      the inclusion of complex features and heterogeneities relevant in the description
      of epidemic diffusion. In this paper, we review recent progresses that integrate
      complex systems and networks analysis with epidemic modelling and focus on the
      impact of the various complex features of real systems on the dynamics of
      epidemic spreading.

PMID- 17502295
TI  - [Lipids and apolipoproteins A1 and B alterations in stroke].
AB  - The purpose of this case-control study was to determine the variations of
      lipoproteins during stroke in adults from Ivory Coast. The survey included 72
      subjects presenting with hemorrhagic stroke and 58 of ischemic stroke, aged of 25
      at 93 years. Lipids parameters have been measured by a colorimetric enzymatic
      method. Apolipoproteins have been determined by immunoturbidimetry. Results
      showed significant decrease of HDL-cholesterol and apoprotein A1 in patients by
      comparison with control subjects. More over, an increase of the atherogenicity
      index expressed as total/HDL-cholesterol or apolipoprotein B /apolipoprotein A1,
      of the triglycerides and apolipoprotein B has been observed.

PMID- 17502294
TI  - [Role of N-linked glycans in the functions of hepatitis C virus envelope
      glycoproteins].
AB  - Hepatitis C virus (HCV) is an enveloped virus and encodes two envelope
      glycoproteins, E1 and E2. E1 and E2 are transmembrane type I proteins with a N
      terminal ectodomain and C-terminal anchor. During their synthesis, E1 and E2
      ectodomains are targeted in the endoplasmic reticulum lumen where they are
      modified by N-linked glycosylation. After their synthesis, E1 and E2 assemble as
      a non-covalent heterodimer. The N-linked glycosylation is based on the
      recognition of specific asparagine residue in the context of the consensus
      sequence Asn-X-Ser/Thr. E1 contains potentially 4 or 5 N-linked glycosylation
      sites and E2 up to 11. Recent data indicated that some glycans of glycoproteins
      E1 and E2 play a major role in protein folding and heterodimer formation. Some N
      linked glycans of E2 were involved in interactions with CD81, a putative cellular
      receptor for HCV. It appeared that N-linked glycans of E1 and E2 played an
      important role of in the viral entry.

PMID- 17502296
TI  - [C3 complement polymorphism in patients suffering from obstructive chronic
      bronchopneumopathy in Tunisia].
AB  - We analysed the C3*S and C3*F polymorphism of the third component of the
      complement (C3), first at the protein level by the electrophoresis of the plasma
      on agarose gel and second on the gene level by the ARMS PCR technique. We
      determined the phenotypic and genotypic frequencies of the C3 on a sample of 90
      patients suffering from the obstructive chronic bronchopneumopathy (OCBP)
      disease. Comparisons have been done with frequencies observed on a control sample
      of 437 healthy individuals from the Tunisian population in order to establish a
      putative correlation between the polymorphism studied and the disease.
      Frequencies of the C3*S and C3*F alleles in OCBP patients are 0,788 and 0,212
      respectively. They are not significantly different from those observed in control
      sample (0,834 and 0,152 respectively). Therefore, no correlation is observed
      between the C3 polymorphism and the risk of developing the OCBP disease.

PMID- 17502297
TI  - [Relevance of the toxoplasma IgG avidity test in the serological surveillance of
      pregnant women].
AB  - In addition to the serological systematic screening tests, kits to measure the
      avidity of toxoplasma IgG antibodies are currently available. Since high-avidity
      IgG toxoplasma antibodies have been shown to exclude recent infection, IgG
      avidity determination is especially useful in ruling out acute infection having
      occurred in the 3-4 prior months of pregnancy. We therefore compared the efficacy
      of two toxoplasma IgG avidity ELISA kits: SFRI (SFRI Laboratoire) and VIDAS Toxo
      IgG avidity kit (bioMerieux). The agreement of the results from the 2 commercial
      assays were analysed using 55 serum samples, in terms of global mother-child
      Toxoplasma results and outcome, specially with light of the results of Toxoplasma
      antenatal, postnatal assays and of clinical follow up of children.

PMID- 17502299
TI  - [Interest of careful blood film observation in haemolytic anaemia diagnosis].
AB  - The discovery of anaemia raises the question of its aetiology. If many causes can
      easily be established, some remain without any accurate diagnosis. The mere issue
      is that their causes can be rare or mechanisms interlinked. A blood film
      examination by the biologist provides helpful elements to guide the diagnosis, it
      can be improved if it is orientated by the physician who prescribed it. Two cases
      of late discovery of haemolytic anaemia, in relation with red cell membrane
      disorders, are reported. They illustrate the interest of a good collaboration
      between the physician and the biologist that lead to diagnosis. The first case is
      about a band-3 protein defect, the second deals with an hereditary dehydrated
      stomatocytosis.

PMID- 17502298
TI  - [XbaI polymorphism of apolipoprotein B gene in a Tunisian population: alleles
      frequencies and relationship with plasma lipid parameters].
AB  - Apolipoprotein B (Apo B) is a component of chylomicrons, low-density lipoproteins
      (LDL), very low density lipoproteins (VLDL), and intermediate-density
      lipoproteins (IDL) and is the ligand for the LDL receptor. Thereby, Apo B plays a
      central role in lipoprotein metabolism and in maintaining the normal homeostasis
      of serum cholesterol levels. Several Apo B restriction fragment length
      polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with
      variation in lipid levels, obesity and/or coronary artery disease. To date, no
      data are available on relationship between XbaI Apo B polymorphism and lipid
      levels in Tunisian population. Here, we report frequencies of the XbaI
      polymorphism of the Apo B gene and we assess the effect of this polymorphism on
      lipid and lipoprotein concentrations in Tunisian population. Blood samples from
      296 Tunisian individuals (112 women and 184 men, aged 51.4+/-9.6 years), were
      analysed for total cholesterol, triglycerides, HDL-cholesterol and
      apolipoproteins A1 and B. In parallel, genotyping by means of polymerase chain
      reaction (PCR) and restriction fragment length polymorphism (RFLP) was performed.
      The XbaI polymorphism was associated with differences in plasma cholesterol
      (p=0.04), triglyceride (p=0.02) and apolipoprotein A1 (p=0.004), individuals with
      the genotype X1X1 have the lowest mean levels and those with the genotype X2X2
      have the highest, with the individuals heterozygous for the polymorphism having
      intermediate levels. According to sex, the XbaI polymorphism effect was only
      observed for triglyceride in men. Thus, the results demonstrate an influence of
      XbaI polymorphism of Apo B gene on serum total-cholesterol, triglycerides and
      apolipoprotein A1 concentrations among Tunisian population.

PMID- 17502300
TI  - [Panton-Valentine leukocidin-producing Staphylococcus aureus responsible for
      necrotizing pneumonia].
AB  - Panton-Valentine leukocidin-producing (PVL) Staphylococcus aureus is responsible
      for a highly lethal necrotizing pneumonia, which occurs predominantly in young
      immunocompetent patients. Hemoptysis and leucopenia often occur but are not
      always present. Detection of PVL gene on S. aureus strains responsible for
      pneumonia should help us to a better understanding of this disease, to improve
      its treatment with antibiotics capable of lower the toxin production and to
      prevent its diffusion to others persons by detection and elimination of a nasal
      S. aureus carriage.

PMID- 17502301
TI  - [Candidemia original diagnosis].
AB  - We reported here a case of fungemia, which was diagnosed by a globular
      numeration: peripheral blood smears showed yeast cells, especially in the
      cytoplasm of neutrophils, with characteristic images of fungal phagocytosis. This
      test induced a prompt diagnosis of fungal septicaemia and the prescription of
      adapted treatment, which probably permitted to rescue the patient from a high
      mortality pathology.

PMID- 17502302
TI  - [A marginal zone-B cell lymphoma revealed by platelet satellitism and lympho
      agglutination phenomenon around atypical lymphocytes].
AB  - A 48-year-old man, with persistent pyrexia, presented with thrombocytopenia and
      lymphocytosis. The peripheral blood smears showed atypical lymphocytes and a
      platelet satellitism phenomenon around atypical lymphocytes associated to lympho
      agglutination. Platelet satellitism was exclusively observed with atypical
      lymphocytes in EDTA-treated blood and at room temperature. This phenomenon was
      not observed when adding normal plasma and could be reproduced several times.
      Flow cytometry analysis of the peripheral blood, cytological and histological
      studies revealed a marginal zone-B cell lymphoma. The mechanism underlying
      platelet satellitism is not fully understood, but is likely to involve an
      immunologic binding of EDTA-dependent antiplatelet autoantibodies directed
      against the platelets glycoprotein IIb/IIIa complex. The association between
      platelet satellitism and lymphoma could also involve a monoclonal Ig secreted by
      lymphoma cells.

PMID- 17502303
TI  - [Low prevalence of anti-centromere antibodies in scleroderma in Morocco (about
      272 cases)].
AB  - PURPOSE: assessment of autoantibodies prevalence during scleroderma within a
      Moroccan population by a retrospective survey. MATERIAL AND METHODS: 272 patient
      (220 cases of systemic sclerosis, 45 cases localised scleroderma and 7 cases of
      mixed connective tissue disease (MCTD)) underwent a screening for antinuclear
      antibodies (ANA) by indirect immunofluorescence (IFI) on Hep-2 cells, followed,
      in 127 cases, by anti-extractable nuclear antigen (ENA) antibodies identification
      using a double immunodiffusion (IDD) method. RESULTS: sixty eight for percent of
      patients presenting with a systemic sclerosis had positive ANA whose
      identification revealed: 23 cases (15.3%) of anti-topoisomerase I, 8 cases (5.3%)
      of anti-centromere (ACA) and 5 cases (3.3%) of anti-U1-RNP antibodies. Out of the
      8 cases of ACA, 3 corresponded to a CREST syndrome. Anti-topoisomerase I
      antibodies were observed in 2 of the 4 patients having an interstitial pulmonary
      syndrome. Anti-U1-RNP antibodies were present in 3/38 patients (7.8%) having a
      systemic sclerosis associated to arthritis. 4/45 patients (9%), presenting with a
      localised scleroderma, had positive ANA, of which 2 were ACA. All patients
      admitted for MCTD had anti-U1-RNP antibodies, coexisting with anti-Sm antibody in
      2 cases. CONCLUSION: the low prevalence of ACA observed in this survey, when
      compared to American, European and Japanese studies, is probably due to ethnic
      variation in frequency of ANA. Indeed, low rates or absence of ACA have been
      reported in south-African, Afro-American, Indian, and Thai studies. The IDD,
      method of reference for detecting of anti-ENA antibodies, identify a small
      fraction of anti-nucleolar aspects of scleroderma. Thus, other methods such as
      ELISA and/or immunoblotting are required to complete their identification.

PMID- 17502304
TI  - [Septicaemia due to Lactobacillus jensenii: bacteriological diagnostic
      orientation].
AB  - Septicaemia concerning Lactobacillus jensenii is exceptional. This bacteria
      commensal of the normal human flora is known for its low pathogenicity. We report
      here the observation of a woman, 50 years old, who was admitted in our service
      for an obstructive acute renal failure and who has presented a septicaemia due to
      L. jensenii, with a favourable issue by use of antibiotics (amoxicillin
      clavulanic acid). This observation permits to report the clinical and
      bacteriological characteristics of L. jensenii. The importance of the
      immunodepressed status (diabetes mellitus, chronic renal failure) and use of the
      endoureteral acts is mentioned.

PMID- 17502306
TI  - [About two cases of trichinellosis caused by Trichinella britovi].
AB  - Trichinellosis is a cosmopolitan zoonosis due to a nematode threadworm,
      Trichinella, essentially Trichinella spiralis. Human cases mostly appeared
      sporadically, sometimes endemically, related with consumption of larva stinking
      meat. We report two cases of trichinellosis, including a myocarditis, caused by
      Trichinella britovi after consumption of frozen wild boar meat.

PMID- 17502305
TI  - [Diagnosis of adult-onset Still's disease: contribution of biology].
AB  - We report one case of adult-onset Still's disease. The diagnosis of this disease
      currently requires application of Yamaguchi's criteria and then exclusion of
      infectious, haematological, autoimmune and neoplasic disorders. The place of
      biology is enhanced with the use of new markers like ferritin and glycosylated
      ferritin. Low percentage of glycosylated ferritin (<20%) in presence of very high
      level of ferritin, unexplained prolonged fever with leukocytosis can help to
      diagnosis. However, glycosylated ferritin is not yet of in routine use.

PMID- 17502307
TI  - [Interest of Prom-Test in the follow-up of premature rupture of membranes].
AB  - The follow-up of premature rupture of membranes requires an hospitalization. The
      aim of this work was to evaluate the interest of the Prom-Test in the action to
      be taken in the case of a suspicion of premature rupture of membranes, a negative
      result allowing to not hospitalize the patient. 105 tests have been carried out
      producing 73 negative results, 23 positive and 9 doubtful. The childbirth,
      started or not, occurred much more quickly when the test is positive. Only 13 of
      the 73 negative tests resulted in a hospitalization including 11 for beginning of
      delivery. A correct use of the test can prevent unnecessary days of
      hospitalization.

PMID- 17502308
TI  - [Propositions of interpretative comments for thyroid function tests].
AB  - In the field of thyroid disease, a number of governmental organisms or
      professional associations have published practice guidelines containing
      laboratory-related recommendations, eg the Haute autorite de la sante (HAS), or
      the American Thyroid Association (ATA). Among the physicians who prescribe
      thyroid function tests, all have not read and memorized all these
      recommendations. In order to help them to better integrate these recommendations
      in their practice, we have composed a thesaurus of ready-made interpretative
      comments, trying to adapt our proposed comments to each possible combination of
      results of TSH and/or free T4 and/or free T3. The laboratorians who would prefer
      to use only the comments based strictly on the recommendations of HAS and/or ATA,
      will be able to select among our comments what is really validated by these two
      organizations. In addition, our work aims at enabling the patients who want it,
      to benefit from written information, which may be complementary to the more often
      spoken information provided by the clinicians.

PMID- 17502309
TI  - Suppression of B lymphopoiesis at a lymphoid progenitor stage in adult rabbits.
AB  - B lymphopoiesis in rabbits is robust early in ontogeny, but is arrested by 16
      weeks of age at which time no proB or preB cells are found in bone marrow (BM).
      To determine if BM cells from adults retain B lymphopoietic potential, we
      transferred BM from adult green fluorescent protein (gfp) transgenic rabbits into
      young rabbits. We found gfp+ preB cells arising in the young recipients,
      indicating that BM cells from adults can differentiate into B cell precursors. We
      identified a population of MHCII-IL-7-binding BM cells in adults that
      collectively expresses Tdt, EBF and Pax5-genes known to be expressed in murine
      lymphoid progenitors. Upon co-culture with OP9 or OP9 delta-like 1+ stromal
      cells, we found that these cells both expanded in number and differentiated into
      B and T cell precursors, respectively, showing that early lymphoid progenitors,
      designated rLP for rabbit lymphoid progenitors, are present within the MHCII-IL-7
      binding BM cell population. Further, IL-7 was required for rLPs to expand and
      differentiate into B cell precursors in vitro. The arrest of B lymphopoiesis in
      adults, however, is not likely due to the absence of IL-7, because the level of
      IL-7 transcripts was higher in BM from adults than in young rabbits. B
      lymphopoiesis was re-initiated in adults after sub-lethal irradiation as shown by
      the reappearance of B cell precursors and the presence of B cell receptor
      excision circles in BM. We conclude that B lymphopoiesis in adults is suppressed
      at a lymphoid progenitor stage (MHCII-IL-7 binding) of development.

PMID- 17502310
TI  - Stability of A-150 plastic ionisation chamber response over a approximately 30-y
      period.
AB  - At the Northern Illinois University Institute for Neutron Therapy at Fermilab,
      the clinical tissue-equivalent ionisation chamber response is measured every
      treatment day using a cesium source that was configured to match readings
      obtained at the National Bureau of Standards. Daily measurements are performed in
      air using the air-to-tissue dose conversion factors given in AAPM Report #7. The
      measured exposure calibration factors have been tabulated and graphed as a
      function of time from 1978 to present. For A-150 plastic ionisation chambers,
      these factors exhibit a sinusoidal variation with a period of approximately 1 y
      and amplitude of +/- 1%. This variation, attributable to the hygroscopic nature
      of A-150 plastic, is correlated with the relative humidity of the facility, and
      is greater than the humidity corrections for gas described in the literature. The
      data suggest that chamber calibration should be performed at least weekly to
      accommodate these variations.

PMID- 17502311
TI  - Determination of new European biometric equations for the calibration of in vivo
      lung counting systems using the Livermore phantom.
AB  - New biometric equations used for assessing the thickness of the overlay plate to
      be added to the physical phantom were determined based on the Computed Tomography
      (CT) chest images of 33 adult males in order to improve the calibration of in
      vivo lung counting systems using the Livermore phantom. These equations are
      specific to systems composed of four germanium detectors with the measured
      subject in supine position. A comparison with the biometric equations used to
      date as reference in France was carried out and proved the usefulness of
      equations directly applicable to the Livermore phantom.

PMID- 17502312
TI  - Design and simulation of a GEM-based TEPC as a neutron REM meter.
AB  - A new plate-like tissue equivalent proportional counter (TEPC) based on the gas
      electron multiplier (GEM) is being developed for use as a neutron rem meter. The
      advantage of a plate-like TEPC over a conventional spherical TEPC is that several
      of the plate-like TEPCs can be stacked together as one unit to increase
      sensitivity to neutrons. A GEM-based TEPC consists of four layers of materials in
      a series: the front cover made of polyethylene, the cathode made of A-150
      plastic, the gas region containing 1/3 atm of P-10 and 1/3 atm of nitrogen and
      the anode made of a copper-coated printed circuit board. The dimensions of the
      TEPC are 10 cm x 10 cm x 1.8 cm. The computer simulation shows that the neutron
      response function of the TEPC closely resembles the response curve of H(10) for
      neutrons with energies between 0.25 eV and 10 MeV. The corresponding sensitivity
      for such a TEPC for a bare (252)Cf neutron source was calculated to be 5.0 cpm
      per microSv h(-1). This sensitivity can be increased many times by simply
      stacking several TEPCs together as one unit.

PMID- 17502313
TI  - Neutron spectrometry around a high-energy electron-positron collider using a
      multi-sphere system with passive detectors.
AB  - At the INFN LNF (Frascati), the 510 MeV electron-positron collider DAPhiNE is
      operating since 1997. The neutron fields in the areas around the accelerator were
      characterised using a Bonner sphere system. The sensitivity of the system was
      extended up to 10(2) MeV by means of a lead loaded 12('') sphere. Recently
      developed thermoluminescence dosemeters (TLDs), with improved neutron sensitivity
      and gamma rejection properties, were used as central detectors. The new TLD-based
      spectrometric system was characterised by irradiation in quasi-monoenergetic or
      radionuclide neutron fields. In addition, numerical verifications with the Monte
      Carlo code MCNP were performed. This work addresses this new TLD-based
      spectrometer and presents the spectral measurements performed in a point of test
      around DAPhiNE. The results are compared with those obtained, in the same point,
      with a previously validated Bonner sphere system based on an active (6)LiI(Eu)
      scintillator.

PMID- 17502314
TI  - Feasibility study of extremity dosemeter based on polyallyldiglycolcarbonate (CR
      39) for neutron exposure.
AB  - In nuclear facilities, some activities such as reprocessing, recycling and
      production of bare fuel rods expose the workers to mixed neutron-photon fields.
      For several workplaces, particularly in glove boxes, some workers expose their
      hands to mixed fields. The mastery of the photon extremity dosimetry is
      relatively good, whereas the neutron dosimetry still raises difficulties. In this
      context, the Institute for Radiological Protection and Nuclear Safety (IRSN) has
      proposed a study on a passive neutron extremity dosemeter based on chemically
      etched CR-39 (PADC: polyallyldiglycolcarbonate), named PN-3, already used in
      routine practice for whole body dosimetry. This dosemeter is a chip of plastic
      sensitive to recoil protons. The chemical etching process amplifies the size of
      the impact. The reading system for tracks counting is composed of a microscope, a
      video camera and an image analyser. This system is combined with the dose
      evaluation algorithm. The performance of the dosemeter PN-3 has been largely
      studied and proved by several laboratories in terms of passive individual neutron
      dosemeter which is used in routine production by different companies. This study
      focuses on the sensitivity of the extremity dosemeter, as well as its performance
      in the function of the level of the neutron energy. The dosemeter was exposed to
      monoenergetic neutron fields in laboratory conditions and to mixed fields in
      glove boxes at workplaces.

PMID- 17502315
TI  - The content of 250Cf and 248Cm in 252Cf neutron sources and the effect on the
      neutron emission rate.
AB  - One of the most common radionuclide neutron sources used for the calibration of
      detectors is (252)Cf. However, these sources also contain (250)Cf, which is
      present in the material from which the sources are made, and (248)Cm, which is
      formed as the daughter of (252)Cf via alpha-decay. Both decay by spontaneous
      fission with longer half-lives than (252)Cf. Consequently, as the source becomes
      older, the emission rate does not follow the decay curve of (252)Cf. Fits have
      been made to emission rate measurements of (252)Cf sources at NPL spanning over
      30 y to deduce their (250)Cf and (248)Cm content. The emission rate of a source
      can be significantly underestimated if the presence of (250)Cf and (248)Cm is not
      taken into account, and this has been investigated for a typical (252)Cf source.
      The importance of this problem to other calibration laboratories and users of
      (252)Cf sources is emphasised.

PMID- 17502316
TI  - Non-equilibrium nucleon spectra from reactions at intermediate energies.
AB  - A new exciton model of pre-equilibrium decay (Monte Carlo Pre-equilibrium) to
      compute spectra of multiparticle emission during an establishment of statistical
      equilibrium in the composite system is proposed. The MCP stage of the calculation
      was included into the standard scheme of the nucleon spectra calculation between
      the intranuclear cascade stage and statistical model stage. A systematic
      comparison of calculation results with experimental spectra of nucleons from
      (p,xn), (p,xp), (n,xn) and (n,xp) reactions in a wide projectile energy region
      from 10 up to 160 MeV for targets from (27)Al up to (209)Bi has been carried out.
      A short description of the MCP model and results obtained are presented.

PMID- 17502317
TI  - Fast neutron beams--prospects for the coming decade.
AB  - The present status of neutron beam production techniques above 20 MeV is
      discussed. Presently, two main methods are used; white beams and quasi
      monoenergetic beams. The performances of these two techniques are discussed, as
      well as the use of such facilities for measurements of nuclear data for
      fundamental and applied research. Recently, two novel ideas on how to produce
      extremely intense neutron beams in the 100-500 MeV range have been proposed.
      Decay in flight of beta delayed neutron-emitting nuclei could provide beam
      intensities five orders of magnitudes larger than present facilities. A typical
      neutron energy spectrum would be essentially monoenergetic, i.e., the energy
      spread is about 1 MeV with essentially no low-energy tail. A second option would
      be to produce beams of (6)He and dissociate the (6)He nuclei into alpha particles
      and neutrons. The basic features of these concepts are outlined, and the
      potential for improved nuclear data research is discussed.

PMID- 17502318
TI  - Development of a quasi-monoenergetic neutron field using the 7Li(p,n)7Be reaction
      in the energy range from 250 to 390 MeV at RCNP.
AB  - A quasi-monoenergetic neutron field using the (7)Li(p,n)(7)Be reaction has been
      developed at the ring cyclotron facility at the Research Center for Nuclear
      Physics (RCNP), Osaka University. Neutrons were generated from a 10-mm-thick Li
      target injected by 250, 350 and 392 MeV protons and neutrons produced at 0
      degrees were extracted into the time-of-flight (TOF) room of 100-m length through
      the concrete collimator of 10 x 12 cm aperture and 150 cm thickness. The neutron
      energy spectra were measured by a 12.7-cm diam x 12.7-cm long NE213 organic
      liquid scintillator using the TOF method. The peak neutron fluence was 1.94 x
      10(10), 1.07 x 10(10) and 1.50 x 10(10) n sr(-1) per muC of 250, 350 and 392 MeV
      protons, respectively. The neutron spectra generated from various thick (stopping
      length) targets of carbon, aluminium, iron and lead, bombarded by 250 and 350 MeV
      protons, were also measured with the TOF method. Although these measurements were
      performed to obtain thick target neutron yields, they are also used as a
      continuous energy neutron field. These neutron fields are very useful for
      characterising neutron detectors, measuring neutron cross sections, testing
      irradiation effects for various materials and performing neutron shielding
      experiments.

PMID- 17502319
TI  - Preliminary studies on neutron conversion coefficients calculated with MCNPX in
      NORMAN voxel phantom.
AB  - Effective dose is the main radiation protection quantity. Progresses in radiation
      studies brought ICRP to revise ICRP 60 recommendations. A new publication,
      already circulated in form of draft, is expected to change some aspects of
      effective dose evaluation method. The organ absorbed doses for neutrons at
      various energies and incidence angles, necessary to estimate the effective dose,
      have been published in ICRU 57 and ICRP 74 reports for ADAM and EVA analytical
      male and female phantoms and similar calculations were also performed, based on
      the MCNP code, for VIP-MAN voxel phantom. The NORMAN voxel phantom, developed on
      the basis of magnetic resonance data of an adult male at HPA (formerly NRPB), is
      an accurate model (with a voxel element of approximately 8 mm(3)), which well
      approximates the standard man and has been already employed for radiation
      protection studies with photons. In the present paper, a modified version, called
      NORMAN-05, including a new organ, the salivary glands (as suggested in the
      mentioned ICRP draft), and a more detailed skeletal description, especially
      devoted to red bone marrow dose evaluation, has been employed with the Monte
      Carlo code MCNPX to calculate neutron conversion coefficients from thermal
      energies to 20 MeV. Some preliminary results, for antero-posterior and postero
      anterior irradiation conditions, are presented and compared with the available
      published data.

PMID- 17502320
TI  - Investigation of combined unfolding of neutron spectra using the UMG unfolding
      codes.
AB  - An investigation of the simultaneous unfolding of data from neutron spectrometers
      using the UMG codes MAXED and GRAVEL has been performed. This approach involves
      combining the data from the spectrometers before unfolding, thereby performing a
      single combined unfolding of all the data to yield a final combined spectrum. The
      study used measured data from three proton recoil counters and also Bonner sphere
      and proton recoil counter responses calculated from their response functions. In
      each case, the spectrum derived from combined unfolding is compared with either
      the spectrum obtained from merging the independently unfolded spectra or the
      spectrum used to calculate the responses. The advantages and disadvantages of
      this technique are discussed.

PMID- 17502321
TI  - Study of the glow curves of TLD exposed to thermal neutrons.
AB  - The glow curves of thermoluminescent dosimeters (TLD600, TLD700 and MCP), exposed
      to a mixed field of thermal neutrons and gamma photons are analysed. The fluence
      values of thermal neutrons used, comparable with those used in radiotherapy,
      allow one to define the reliability of the TLDs, in particular the most sensitive
      MCP, in this radiation field and to get information on the dose absorbed values.
      The glow curves obtained have been deconvoluted using general order kinetics and
      the observed differences for the different LET components have been analysed. In
      particular, the ratio of the n(0) parameter of two different peaks seems to allow
      to discriminate the different contributions of neutrons and gamma photons in the
      beam.

PMID- 17502322
TI  - Variable aneuploidy mechanisms in embryos from couples with poor reproductive
      histories undergoing preimplantation genetic screening.
AB  - BACKGROUND: Preimplantation genetic screening (PGS) is used to determine the
      chromosome status of human embryos from patients with advanced maternal age
      (AMA), recurrent miscarriage (RM) or repeated implantation failure (RIF).
      METHODS: Embryos from 47 such couples were investigated for chromosomes 13, 15,
      16, 18, 21 and 22 using fluorescence in situ hybridization with two rounds of
      hybridization. The investigation included parental lymphocyte work-up, the
      screening of blastomeres on day 3 and full follow-up on day 5/6 of untransferred
      embryos. RESULTS: The outcome of 60 PGS cycles is described, in which 523 embryos
      were biopsied; 91% gave results, of which 18% were diploid for all the
      chromosomes tested and 82% were abnormal. The pregnancy rate per cycle that
      reached the biopsy stage was 27%, and 30% per embryo transfer. Satisfactory
      follow-up was obtained from 353 embryos; all those diagnosed as abnormal were
      confirmed as such, although two false-positives were detected in relation to
      specific chromosome abnormalities. Meiotic errors were identified in 16% of
      embryos. Between the RM, AMA and RIF groups, there was a significant difference
      in the distribution of embryos that were uniformly abnormal and of those with
      meiotic errors; with an almost 3-fold increase in meiotic errors in the first two
      groups compared with the RIF group. CONCLUSIONS: This complete investigation has
      identified significant differences between referral groups concerning the origin
      of aneuploidy in their embryos.

PMID- 17502323
TI  - Light cigarette smoking impairs coronary microvascular functions as severely as
      smoking regular cigarettes.
AB  - BACKGROUND: Smoking is the most prevalent and most preventable risk factor for
      cardiovascular diseases. Smoking low-tar, low-nicotine cigarettes (light
      cigarettes) would be expected to be less hazardous than smoking regular
      cigarettes owing to the lower nicotine and tar yield. OBJECTIVE: To compare the
      chronic and acute effects of light cigarette and regular cigarette smoking on
      coronary flow velocity reserve (CFVR). METHODS: 20 regular cigarette smokers
      (mean (SD) age 24.8 (5.0)), 20 light cigarette smokers (mean age 25.6 (6.4)), and
      22 non-smoker healthy volunteers (mean age 25.1 (4.2)) were included. First, each
      subject underwent echocardiographic examination, including CFVR measurement,
      after a 12 hour fasting and smokeless period. Two days later, each subject smoked
      two of their normal cigarettes in a closed room within 15 minutes. Finally,
      within 20-30 minutes, each subject underwent an echocardiographic examination,
      including CFVR measurement. RESULTS: Mean (SD) CFVR values were similar in light
      cigarette and regular cigarette smokers and significantly lower than in the
      controls (2.68 (0.50), 2.65 (0.61), 3.11 (0.53), p = 0.013). Before and after
      smoking a paired t test showed that smoking two light cigarettes acutely
      decreased the CFVR from 2.68 (0.50) to 2.05 (0.43) (p = 0.001), and smoking of
      two regular cigarettes acutely decreased CFVR from 2.65 (0.61) to 2.18 (0.48) (p
      = 0.001). CONCLUSION: Smoking low-tar, low-nicotine cigarettes impairs the CFVR
      as severely as smoking regular cigarettes. CFVR values are similar in light
      cigarette and regular cigarette smokers and significantly lower than in controls.

PMID- 17502324
TI  - Virtual histology.
AB  - As a luminogram, coronary angiography provides a good overview of the coronary
      artery tree. Using quantitative coronary measurements, the degree of coronary
      obstruction can be determined. The limitation of coronary angiography is that it
      does not provide information on the arterial wall structure and therefore cannot
      assess the extent of atherosclerosis. Knowledge about adaptive coronary
      remodelling processes as compensatory enlargement of the coronary artery has
      focused diagnostic interest on the non-stenotic lesions of the coronary tree.
      Intravascular ultrasound (IVUS) can reveal discrepancies between the extent of
      coronary atherosclerosis and angiography imaging by in vivo plaque imaging.
      Spectrum analysis of IVUS-derived radiofrequency (RF) data enables a more
      detailed analysis of plaque composition and morphology. Preliminary in vitro
      studies correlated four histological plaque components with a specific spectrum
      analysis of the RF data. The different components (fibrous, fibrofatty, necrotic
      core and dense calcium) are colour coded. Coronary tissue maps were reconstructed
      from RF data using IVUS-Virtual Histology (VH IVUS) software (Real-Time VH,
      Volcano Corporation, Rancho Cordova, California, USA). VH IVUS has the potential
      to detect high-risk lesions and can provide new insights into the pathophysiology
      of coronary artery disease. VH IVUS allows the differentiation of different
      lesion types based on information derived from histopathology. The in vivo
      specific histological analysis of coronary atherosclerosis may allow better
      stratification of treatment of patients with coronary artery disease.

PMID- 17502325
TI  - Selection bias resulting from the requirement for prior consent in observational
      research: a community cohort of people with ischaemic heart disease.
AB  - OBJECTIVE: To evaluate differences between adults who consent to participate in
      observational research and those who do not. DESIGN: Prospective, population
      based cohort study. SETTING: 35 randomised Irish general practices. PARTICIPANTS:
      1609 adults with ischaemic heart disease identified in 2000-1. INTERVENTION:
      Medical records search, postal questionnaire and consent form in 2005-6. MAIN
      OUTCOME MEASURES: Differences in demographic and prognostic risk factors between
      consenters and non-consenters. RESULTS: At follow-up, charts were located for
      1592 patients (98.9%). Questionnaires were sent to 1269 patients and 876 were
      returned (69%). Of these, 574 (65.5%) gave consent for participation in further
      research. Logistic regression identified four characteristics as independently
      positively predictive of consent to participation in further research among
      questionnaire responders: having undergone percutaneous transluminal coronary
      angioplasty was associated with an increased odds of consent, with an odds ratio
      (OR) of 1.77 (95% CI 1.09 to 2.86), as was a last recorded blood pressure <140/90
      mm Hg (OR = 1.45 (1.00 to 2.09)), a last recorded total cholesterol level <5
      mmol/l (OR = 1.71 (1.16 to 2.54)) and being an ex-smoker rather than a current
      smoker or non-smoker (OR = 1.73 (1.17 to 2.57)). CONCLUSIONS: This research
      demonstrates the potential impact of consent bias in observational research on
      ischaemic heart disease, a disease of everyday clinical importance in Europe. It
      demonstrates that clinically important prognostic variables may be associated
      with consent preferences. Future cohorts, dependent upon prior written consent,
      may contain disproportionate numbers of those who have made healthy lifestyle
      decisions, have previously benefited from treatment or whose clinical risk
      factors are already well managed. As a result, the generalisability of such
      research may be diminished and the effects of treatments over- or underestimated.

PMID- 17502326
TI  - Early impact of insulin treatment on mortality for hyperglycaemic patients
      without known diabetes who present with an acute coronary syndrome.
AB  - OBJECTIVE: To determine the effect of insulin for the management of
      hyperglycaemia in non-diabetic patients presenting with acute coronary syndrome.
      METHODS: An observational study from the MINAP (National Audit of Myocardial
      Infarction Project) database during 2003-5 in 201 hospitals in England and Wales.
      Patients were those with a final diagnosis of troponin-positive acute coronary
      syndrome who were not previously known to have diabetes mellitus and whose blood
      glucose on admission was > or = 11 mmol/l. The main outcome measure was death at
      7 and 30 days. RESULTS: Of 38,864 patients who were not previously known to be
      diabetic, 3835 (9.9%) had an admission glucose > or = 11 mmol/l. Of patients
      having a clear treatment strategy, 36% received diabetic treatment (31% with
      insulin). Mortality at 7 and 30 days was 11.6% and 15.8%, respectively, for those
      receiving insulin, and 16.5% and 22.1%, respectively, for those who did not.
      Compared with those who received insulin, after adjustment for age, gender, co
      morbidities and admission blood glucose concentration, patients who were not
      treated with insulin had a relative increased risk of death of 56% at 7 days and
      51% at 30 days (HR 1.56, 95% CI 1.22 to 2.0, p<0.001 at 7 days; HR 1.51, 95% CI
      1.22 to 1.86, p<0.001 at 30 days). CONCLUSION: In non-diabetic patients with
      acute coronary syndrome and hyperglycaemia, treatment with insulin was associated
      with a reduction in the relative risk of death, evident within 7 days of
      admission, which persists at 30 days.

PMID- 17502327
TI  - Left atrial Frank-Starling law assessed by real-time, three-dimensional
      echocardiographic left atrial volume changes.
AB  - BACKGROUND: The Frank-Starling law describes the relation between left
      ventricular volume and function. However, only a few studies have described the
      relation between left atrial volume (LAV) and function. OBJECTIVE: To describe an
      LA Frank-Starling law by studying changes in LAV measured by real-time, three
      dimensional echocardiography (RT3DE). METHODS: LAV was calculated by RT3DE in 70
      patients at end-systole (LAV(max)), end-diastole (LAV(min)) and pre-atrial
      contraction (LAV(pre-A)). According to LAV(max), patients were classified into
      three groups: LAV(max) <50 ml (group I), LAV(max) 50-70 ml (group II) and
      LAV(max) >70 ml (group III). Calculated indices of LA pump function were active
      atrial stroke volume (SV), defined as LAV(pre-A) - LAV(min), and active atrial
      emptying fraction (EF), defined as active atrial SV/LAV(pre-A) x100% RESULTS:
      Active atrial SV was significantly higher in group II than in group I (mean (SD)
      19.0 (9.2) vs 8.2 (4.9) ml, p<0.0001), in group III it was non-significantly
      lower than in group II (16.7 (12.5) vs 19.0 (9.2) ml). Active atrial SV
      correlated well with LAV(pre-A) (r = 0.56, p<0.001), but decreased with larger
      LAV(pre-A). Active atrial EF tended to be higher in group II than in group I
      (43.1 (18.2) vs 33.2 (17.5), p<0.10), in group III it was significantly lower
      than in group II (26.2 (18.5) vs 43.1 (18.2), p<0.01). CONCLUSION: A Frank
      Starling mechanism in the left atrium could be described by RT3DE, shown by an
      increase in LA contractility in response to an increase in LA preload up to a
      point, beyond which LA contractility decreased.

PMID- 17502328
TI  - Prediction of cognitive dysfunction after resuscitation from out-of-hospital
      cardiac arrest using serum neuron-specific enolase and protein S-100.
AB  - BACKGROUND: More than 50% of patients initially resuscitated from out-of-hospital
      cardiac arrest die in hospital. OBJECTIVE: To investigate the prognostic value of
      serum protein S-100 and neuron-specific enolase (NSE) concentrations for
      predicting (a) memory impairment at discharge; (b) in-hospital death, after
      resuscitation from out-of-hospital cardiac arrest. METHODS: In a prospective
      study of 143 consecutive survivors of out-of-hospital cardiac arrest, serum
      samples were obtained within 12, 24-48 and 72-96 hours after the event. S-100 and
      NSE concentrations were measured. Pre-discharge cognitive assessment of patients
      (n = 49) was obtained by the Rivermead Behavioural Memory Test (RBMT). The
      relationship between biochemical brain marker concentrations and RBMT scores, and
      between marker concentrations and the risk of in-hospital death was examined.
      RESULTS: A moderate negative relationship was found between S-100 concentration
      and memory test score, at all time points. The relationship between NSE and
      memory test scores was weaker. An S-100 concentration >0.29 microg/l at time B
      predicted moderate to severe memory impairment with absolute specificity (42.8%
      sensitivity). S-100 remained an independent predictor of memory function after
      adjustment for clinical variables and cardiac arrest timing indices. NSE and S
      100 concentrations were greater in patients who died than in those who survived,
      at all time points. Both NSE and S-100 remained predictors of in-hospital death
      after adjustment for clinical variables and cardiac arrest timing indices. The
      threshold concentrations yielding 100% specificity for in-hospital death were S
      100: 1.20 microg/l (sensitivity 44.8%); NSE 71.0 microg/l (sensitivity 14.0%).
      CONCLUSIONS: Estimation of serum S-100 concentration after out-of-hospital
      cardiac arrest can be used to identify patients at risk of significant cognitive
      impairment at discharge. Serum S-100 and NSE concentrations measured 24-48 hours
      after cardiac arrest provide useful additional information.

PMID- 17502329
TI  - Effect of drug combinations on admission for recurrent myocardial infarction.
AB  - OBJECTIVE: To determine the effect of the number of different drugs with
      adherence to medication of at least 70% on recurrent admission for myocardial
      infarction (MI) in patients with a history of MI. DESIGN: Nested case-control
      study in a dynamic cohort. SETTING: PHARMO database that contains pharmacy
      dispensing records and hospital discharge records of 350,000 Dutch citizens.
      SUBJECTS: All patients admitted to hospital for first MI (ICD-9 410) from 1991 to
      2000 with at least a 30-day survival after admission. Cases were admitted for
      recurrent MI and were matched for age, sex, and year of admission with controls
      who did not have a recurrent MI. MAIN OUTCOME MEASURE(S): Odds ratio with 95% CI
      for admission for recurrent MI. Exposure was the number of preventive drugs
      (antiplatelet agents, statins and beta blockers or ACE inhibitors) used for at
      least 70% of the time. RESULTS: 389 cases were matched with 2344 controls. The
      use of one drug was associated with a 6% odds reduction (95% CI 30% reduction to
      28% increase) for admission for recurrent MI. The use of two or three drugs was
      associated with reductions of 26% and 41% (47% reduction to 3% increase and 6% to
      63% reduction, respectively). Addition of one drug caused a 16% reduction (4% to
      26%). CONCLUSIONS: Multiple drug treatment decreases admissions for recurrent MI
      in patients with a history of MI. Every addition of a drug, regardless of drug
      class, reduces the risk even further. These results support the treatment
      strategies as applied in daily practice.

PMID- 17502330
TI  - A parent-completed respiratory questionnaire for 1-year-old children:
      repeatability.
AB  - BACKGROUND AND AIMS: There are few standardised questionnaires for the assessment
      of respiratory symptoms in preschool children. We have developed and tested the
      short-term repeatability of a postal questionnaire on respiratory symptoms for 1
      year-old children. METHODS: A newly developed postal questionnaire for the
      assessment of wheeze and other respiratory symptoms was sent to parents of a
      population-based random sample of 4300 children aged 12-24 months. After an
      interval of 3 months, a random sample of 800 respondents received the
      questionnaire a second time. The responses were compared using Cohen's kappa
      (kappa) to assess agreement corrected for chance. RESULTS: The first
      questionnaire was returned by 3194 (74%) families, the second one by 460/800
      (58%). Repeatability was excellent (kappa 0.80-0.96) for questions on household
      characteristics, environmental exposures and family history, good (kappa 0.61
      0.80) for questions on prevalence, severity and treatment of wheeze, and moderate
      (kappa 0.39-0.66) for chronic cough and upper respiratory symptoms. CONCLUSIONS:
      This short postal questionnaire designed for use in population-based studies has
      excellent repeatability for family and household characteristics and good
      repeatability for questions on wheeze. Short-term changes in symptom status might
      be responsible for variable answers on recent chronic cough and upper respiratory
      symptoms. Overall, the questionnaire is a valuable instrument for community-based
      research on respiratory symptoms in 1 to 2-year-old children.

PMID- 17502331
TI  - The 2004 Olympic Games: physiotherapy services in the Olympic Village polyclinic.
AB  - OBJECTIVE: First, to document the injuries sustained during the 2004 Olympic
      Games in a sample of patients visiting the physiotherapy department of the
      Olympic Village polyclinic. Second, to provide information and data about the
      physiotherapy services for planning future Olympics and other mass gatherings.
      DESIGN: Observational study. SETTING: Olympic Village polyclinic. PARTICIPANTS:
      457 patients aged 15-72 years visited the physiotherapy department from 30 July
      through 30 August. RESULTS: The department's workload was at a peak during the
      last 15 days of the Olympic Games (periods B and C). The most common injuries
      were overuse injuries (47.3%). The most common pathology for physiotherapy
      attendance was myofascial pain/muscle spasm (32.5%), followed by tendinopathy
      (19.2%) and ligament sprain (18.7%). The most prevalent site of injury was the
      thigh (21%), followed by the knee (14.1%) and the lumbar spine (13.5%). Most
      injuries had symptoms of <7 days' duration. The geographical region with the
      greatest demand for physiotherapy services was Africa (40.6%). Most patients were
      athletes (74.8%), although team officials accounted for a considerable number
      (14%). CONCLUSIONS: The smallest national teams--especially those from developing
      countries--were more likely to take advantage of services, probably because the
      larger teams had their own medical and physiotherapy staff. The characteristics
      of patients, their sustained injuries and the subsequent treatment varied by the
      accreditation status of the patients. The physiotherapy department's workload was
      dependent on the Olympic Games schedule.

PMID- 17502332
TI  - Impact of low-intensity isocapnic hyperpnoea on blood lactate disappearance after
      exhaustive arm exercise.
AB  - OBJECTIVE: To investigate the impact of low-intensity isocapnic hyperpnoea (IH)
      on blood lactate disappearance after exhaustive arm exercise in comparison with
      passive and active recovery using the previously loaded muscle group. DESIGN:
      Randomised, crossover trial. SETTING: Institute for Sports Medicine.
      PARTICIPANTS: 18 healthy non-smoking and physically active male subjects.
      INTERVENTIONS: Subjects performed three arm cranking tests to volitional
      exhaustion on 3 different days at least 48 h apart. Arm exercise was randomly
      followed by 30 min of passive recovery (PR), active arm cranking (AC) at 30% of
      peak power output or ventilatory recovery (VR) by means of IH at 30% of 12 s
      maximal voluntary ventilation. Blood lactate concentrations were measured every 2
      min during recovery. MAIN OUTCOME MEASUREMENTS: Blood lactate disappearance
      during the three different recovery strategies. RESULTS: No significant
      differences in blood lactate concentrations were found between interventions PR,
      AC and VR during the whole measurement period. Mean (SD) peak lactate
      concentrations were 11.09 (1.98) mmol/l for PR, 11.13 (1.44) mmol/l for AC and
      11.25 (1.93) mmol/l for VR. At the end of the recovery period measured lactate
      concentrations were 4.35 (1.56) mmol/l for PR, 3.77 (1.60) mmol/l for AC and 4.09
      (1.35) mmol/l for VR. Moreover, all other variables measured were not
      significantly different, with the exception of higher average recovery heart
      rates during AC (116 (9) bpm) and VR (111 (17) bpm) compared with PR (93 (11)
      bpm). CONCLUSION: Low-intensity IH seems not to enhance blood lactate
      disappearance after exhaustive arm exercise compared with passive or active
      recovery using the previously loaded muscle group. The magnitude of the involved
      muscle mass appears critical to effective active recovery.

PMID- 17502333
TI  - Injuries in the Victorian thoroughbred racing industry.
AB  - There is increasing concern in Australia about safety in the thoroughbred racing
      industry, but there has been no reported analysis of injury data. This review
      analyses injury and workers' compensation data recorded in Victoria. On the basis
      of the results, it is recommended that the injury and incident data collection
      systems are improved such that they are not only more complete but also
      accumulate more detailed information about the location of an incident or injury
      event, the activity at the time of the incident or injury event, and factors that
      may have influenced the occurrence.

PMID- 17502334
TI  - Anabolic androgenic steroids induce micronuclei in buccal mucosa cells of
      bodybuilders.
AB  - OBJECTIVE: To evaluate genotoxicity of anabolic androgenic steroids (AAS) in male
      bodybuilders by a micronucleus assay in buccal mucosa cells. METHODS: 11 male
      bodybuilders volunteered to participate in this study and two groups were formed:
      group 1 (n = 6), without AAS consumption and group 2 (n = 5), with AAS
      consumption. A sample of buccal epithelium was taken from each participant once a
      week for 6 weeks. Samples were fixed, stained and analysed by a light microscope,
      and 2000 cells were counted from each slide. Results are expressed as
      micronucleated cells (MNC) per 1000 cells and were analysed by the Mann-Whitney U
      test and Wilcoxon's test. RESULTS: A marked increased in MNC was seen in
      bodybuilders with AAS consumption compared with those without AAS consumption
      (mean (SD) 4.1 (2.4) MNC/1000 cells vs 0.4 (0.4) MNC/1000 cells, respectively;
      p<0.004). Intragroup comparisons showed no differences in the MNC frequencies
      during the sampling time in group 1, whereas the MNC frequency in group 2 varied
      significantly, reaching the highest MNC frequencies in the third and fourth week
      of sampling (5.9 (2.4) MNC/1000 cells; 5.8 (1.8) MNC/1000 cells, respectively);
      frequency in the first sampled week was 1.1 (0.1) MNC/1000 cells. Significant
      differences in all sampled weeks were found between the two groups. CONCLUSION:
      AAS consumption increased the frequency of MNC from buccal mucosa in
      bodybuilders.

PMID- 17502335
TI  - Using provenance to manage knowledge of in silico experiments.
AB  - This article offers a briefing in one of the knowledge management issues of in
      silico experimentation in bioinformatics. Recording of the provenance of an
      experiment-what was done; where, how and why, etc. is an important aspect of
      scientific best practice that should be extended to in silico experimentation. We
      will do this in the context of eScience which has been part of the move of
      bioinformatics towards an industrial setting. Despite the computational nature of
      bioinformatics, these analyses are scientific and thus necessitate their own
      versions of typical scientific rigour. Just as recording who, what, why, when,
      where and how of an experiment is central to the scientific process in laboratory
      science, so it should be in silico science. The generation and recording of these
      aspects, or provenance, of an experiment are necessary knowledge management goals
      if we are to introduce scientific rigour into routine bioinformatics. In Silico
      experimental protocols should themselves be a form of managing the knowledge of
      how to perform bioinformatics analyses. Several systems now exist that offer
      support for the generation and collection of provenance information about how a
      particular in silico experiment was run, what results were generated, how they
      were generated, etc. In reviewing provenance support, we will review one of the
      important knowledge management issues in bioinformatics.

PMID- 17502336
TI  - Knowledge networks in the age of the Semantic Web.
AB  - The Web has become the major medium for various communities to share their
      knowledge. To this end, it provides an optimal environment for knowledge
      networks. The web offers global connectivity that is virtually instantaneous, and
      whose resources and documents can easily be indexed for easy searching. In the
      coupled realms of biomedical research and healthcare, this has become especially
      important where today many thousands of communities already exist that connect
      across academia, hospitals and industry. These communities also rely on several
      forms of knowledge assets, including publications, experimental data, domain
      specific vocabularies and policies. Web-based communities will be one of the
      earlier beneficiaries of the emerging Semantic Web. With the new standards and
      technologies of the Semantic Web, effective utilization of knowledge networks
      will expand profoundly, fostering new levels of innovation and knowledge.

PMID- 17502337
TI  - Microtubules regulate PI-3K activity and recruitment to the phagocytic cup during
      Fcgamma receptor-mediated phagocytosis in nonelicited macrophages.
AB  - Phagocytosis is a complex sequence of events involving coordinated remodeling of
      the plasma membrane with the underlying cytoskeleton. Although the role of the
      actin cytoskeleton is becoming increasingly elucidated, the role of microtubules
      (MTs) remains poorly understood. Here, we examine the role of MTs during FcgammaR
      mediated phagocytosis in RAW264.7 mouse macrophages. We observe that MTs extend
      into the phagosomal cups. The MT-depolymerizing agents, colchicine and
      nocodazole, cause a sizeable reduction in phagocytosis of large particles in
      RAW264.7 cells. Phagocytosis in primed macrophages is unaffected by MT
      depolymerizing agents. However, activation of macrophages coincides with an
      increased population of drug-stable MTs, which persist in functional phagocytic
      cups. Scanning electron microscopy analysis of unprimed macrophages reveals that
      pseudopod formation is reduced markedly following colchicine treatment, which is
      not a consequence of cell rounding. MT depolymerization in these cells does not
      affect particle binding, Syk, or Grb2-associated binder 2 recruitment or
      phosphotyrosine accumulation at the site of phagocytosis. Ras activation also
      proceeds normally in macrophages treated with colchicine. However, MT disruption
      causes a decrease in accumulation of AKT-pleckstrin homology-green fluorescent
      protein, a probe that binds to PI-3K products at the sites of particle binding. A
      corresponding decline in activated AKT is observed in colchicine-treated cells
      using immunoblotting with a phospho-specific-AKT (ser473) antibody. Furthermore,
      the translocation of the p85alpha regulatory subunit of PI-3K is reduced at the
      phagocytic cup in colchicine-treated cells. These findings suggest that MTs
      regulate the recruitment and localized activity of PI-3K during pseudopod
      formation.

PMID- 17502338
TI  - Modulation of NFAT-dependent gene expression by the RhoA signaling pathway in T
      cells.
AB  - We have reported previously that p115Rho guanine nucleotide exchange factor, its
      upstream activator Galpha13, and its effector RhoA are able to inhibit HIV-1
      replication. Here, we show that RhoA is able to inhibit HIV-1 gene expression
      through the NFAT-binding site in the HIV long-terminal repeat. Constitutively
      active NFAT counteracts the inhibitory activity of RhoA, and inhibition of NFAT
      activation also inhibits HIV-1 gene expression. We have shown further that RhoA
      inhibits NFAT-dependent transcription and IL-2 production in human T cells. RhoA
      does not inhibit nuclear localization of NFAT but rather, inhibits its
      transcriptional activity. In addition, RhoA decreases the level of acetylated
      histone H3, but not NFAT occupancy, at the IL-2 promoter. These data suggest that
      activation of RhoA can modulate IL-2 gene expression by inhibiting the
      transcriptional activity of NFAT and chromatin structure at the IL-2 promoter
      during T cell activation.

PMID- 17502339
TI  - Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in
      macrophage activation.
AB  - Macrophage phenotype and activation are regulated by cytokines that use the Jak
      STAT signaling pathway, microbial recognition receptors that include TLRs, and
      immunoreceptors that signal via ITAM motifs. The amplitude and qualitative nature
      of macrophage activation are determined by crosstalk among these signaling
      pathways. Basal ITAM signaling restrains macrophage responses to TLRs and other
      activating ligands, whereas strong ITAM signals synergize with the same ligands
      to activate cells strongly. Similarly, basal ITAM signaling augments IFN
      signaling and function of receptor activator of NF-kappaB, but extensive ITAM
      activation inhibits Jak-STAT signaling. Thus, intensity and duration of ITAM
      signaling determine whether ITAM-coupled receptors augment or attenuate TLR and
      Jak-STAT responses. IFN-gamma synergizes with TLRs in part by suppressing TLR
      induced feedback inhibition, mediated by IL-10 and Stat3, by a mechanism that
      depends on glycogen synthase kinase (GSK)3 regulation of AP-1 and CREB. IFN-gamma
      suppresses TLR2 and TLR4 induction/activation of AP-1 by overlapping mechanisms
      that include regulation of MAPKs, GSK3-dependent suppression of DNA binding, and
      decreased Fos and Jun protein expression and stability. IFN-gamma suppression of
      TLR-induced activation of AP-1 and downstream target genes challenges current
      concepts about the inflammatory role of AP-1 proteins in macrophage activation
      and is consistent with a role for AP-1 in the generation of noninflammatory
      osteoclasts. Jak-STAT, TLR, and ITAM pathways are basally active in macrophages
      and strongly induced during innate responses. Thus, signal transduction crosstalk
      is regulated in a dynamic manner, which differs under homeostatic and pathologic
      conditions, and dysregulation of signal transduction crosstalk may contribute to
      pathogenesis of chronic inflammatory diseases.

PMID- 17502340
TI  - Impact of physicochemical and structural properties on the pharmacokinetics of a
      series of alpha1L-adrenoceptor antagonists.
AB  - A rational drug discovery process was initiated to design a potent and prostate
      selective alpha1(L)-adrenoceptor antagonist with pharmacokinetic properties
      suitable for once a day administration after oral dosing, for the treatment of
      benign prostatic hyperplasia. Two series of compounds based on a quinoline or
      quinazoline template were identified with appropriate pharmacology. A series of
      high molecular weight cations with high hydrogen-bonding potential had extensive
      in vivo clearance, despite demonstrating metabolic stability. Studies in the
      isolated perfused rat liver and fresh rat hepatocytes indicated that active
      transport protein-mediated hepatobiliary elimination is an efficient clearance
      process for these compounds. A reduction in molecular weight and hydrogen-bonding
      potential resulted in a second series of compounds with in vivo hepatic clearance
      predictable from in vitro metabolic clearance. Initially, lipophilicity was
      reduced within this second series to reduce metabolic clearance and increase
      elimination half-life. However, this strategy also resulted in a concomitant
      reduction in volume of distribution and a negligible effect on prolonging half
      life. An alternative strategy was to increase the intrinsic metabolic stability
      of the molecule by careful structural modifications while maintaining
      lipophilicity. Replacement of the metabolically vulnerable morpholine side chain
      resulted in identification of UK-338,003, (N-[2-(4-amino-6,7-dimethoxy-5-pyridin
      2-yl-quinazolin-2-yl)-1,2,3,4-tetrahydro-isoquinolin-5-yl]-methanesulfonamide),
      which fulfilled the objectives of the discovery program with suitable
      pharmacology (human prostate alpha1(L) pA(2) of 9.2 with 25-fold selectivity over
      rat aorta alpha1(D)) and sufficiently long elimination half-life in human
      volunteers (11-17 h) for once a day administration.

PMID- 17502341
TI  - The role of monocarboxylate transporter 2 and 4 in the transport of gamma
      hydroxybutyric acid in mammalian cells.
AB  - Monocarboxylate transporter 1 (MCT1) is an important determinant of the renal
      transport of the drug of abuse, gamma-hydroxybutyric acid (GHB). The objective of
      this study was to investigate the role of MCT2 and MCT4, present in tissues
      including intestine, kidney, skeletal muscle, and brain, in the membrane
      transport of GHB and the MCT substrate l-lactate. mRNA and protein of MCT2 and
      MCT4 were expressed in MDA-MB231 cells, as detected by reverse transcription
      polymerase chain reaction and Western blot analysis; MCT1 and MCT3 were not
      detected. The uptake of GHB or l-lactate by MDA-MB231 cells was pH-dependent but
      not sodium-dependent. The concentration-dependent uptake of GHB was best fitted
      to a single-transporter model with a diffusional clearance component (K(m) of
      17.6 +/- 1.5 mM, V(max) of 50.6 +/- 9.0 nmol x mg(-1) min(-1) and diffusional
      clearance of 0.20 +/- 0.07 microl x mg(-1) min(-1)). On the other hand, the
      concentration-dependent uptake of l-lactate was best fitted to a two-transporter
      model (K(m) of 21 +/- 2.5 and 3.0 +/- 1.5 mM, and V(max) of 268 +/- 72 and 62.9
      +/- 42.2 nmol x mg(-1)min(-1), respectively). The uptake of GHB and l-lactate was
      inhibited by MCT inhibitors alpha-cyano-4-hydroxycinnamate (CHC), phloretin, and
      p-chloromercuribenzoic acid; CHC inhibited GHB and l-lactate uptake with IC(50)
      values of 1.71 +/- 0.39 and 0.71 +/- 0.11 mM, respectively. Small interfering RNA
      treatment to silence MCT2 or MCT4 significantly decreased their protein
      expression and the uptake of l-lactate and GHB; however, the decrease in GHB
      uptake with MCT2 inhibition was smaller than that for MCT4. This investigation
      demonstrated that GHB is a substrate for both MCT2 and MCT4; these transporters
      may be important in the nonlinear disposition of GHB, as well as influencing its
      tissue distribution.

PMID- 17502342
TI  - Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8)
      transport edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one) and its
      sulfate conjugate.
AB  - 3-Methyl-1-phenyl-2-pyrazolin-5-one (MCI-186; edaravone), a novel free radical
      scavenger, is used for the treatment of acute cerebral infarction. After
      marketing, a few cases of acute renal failure were reported in patients following
      treatment with this drug. Because edaravone is mainly excreted into the urine
      following conjugation to glucuronide or sulfate, the renal excretion mechanisms
      of edaravone should help provide important information when considering the
      clinical cases. We examined the transport of edaravone and its sulfate and
      glucuronide conjugates via human organic anion transporter 1 (hOAT1) and 3
      (hOAT3), expressed on the basolateral membranes of proximal tubules. The hOAT1-
      and hOAT3-transfected human embryonic kidney (HEK)-293 cells exhibited a markedly
      higher uptake of edaravone sulfate and a slightly higher uptake of edaravone than
      vector-transfected cells. The K(m) values of edaravone sulfate uptake by hOAT1
      and hOAT3 were 11 and 15 microM, respectively. Estimation of the relative
      contribution of hOAT1 and hOAT3 using reference compounds suggested that hOAT1
      and hOAT3 might contribute to the renal uptake of edaravone sulfate to the same
      extent. However, edaravone and its sulfate showed no cytotoxicity toward both
      hOAT1-HEK and control cells, suggesting that higher uptake in hOAT1-HEK did not
      associate with cytotoxicity of these compounds. In conclusion, our results
      suggest that both hOAT1 and hOAT3 are responsible for the basolateral uptake of
      edaravone sulfate in the kidney.

PMID- 17502343
TI  - Current treatment of hepatitis B.

PMID- 17502344
TI  - Temporal relationship between hepatitis B virus enhancer II/basal core promoter
      sequence variation and risk of hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: To investigate the temporal relationship between sequence
      variation in the enhancer II (EnhII), basal core promoter (BCP), and precore
      regions of hepatitis B virus (HBV) and the risk of hepatocellular carcinoma
      (HCC), we conducted a nested case-control study within a cohort of 4841 male HBV
      carriers who were recruited during the period 1988-1992. METHODS: The HBV DNA
      sequence was determined in baseline blood samples taken from 132 incident cases
      and 204 controls. Base exchanges during follow-up in 71 cases were compared with
      81 controls with samples taken during a similar length of follow-up. RESULTS:
      Nine single nucleotide polymorphisms in the EnhII/BCP regions (six of which were
      genotype C HBV related) were associated with subsequent risk of HCC. The strength
      of these associations decreased as the lag time between baseline measurement and
      diagnosis increased over 3 years. However, an increased disease risk in subjects
      with BCP double variants (mostly T1762/A1764) or genotype C HBV-related variants
      was evident 9 years or more before diagnosis. The BCP double variants (odds
      ratio, 1.92 (95% confidence interval, 1.14 to 3.25)) were statistically
      significantly associated with HCC risk even after adjusting for alanine
      aminotransferase levels, antibodies against HBV e antigen, HBV genotype, HBV
      viral load, and other sequence variants. Longitudinal analysis indicated that the
      increased HCC risks for at-risk sequence variants were attributable to the
      persistence of these variants. CONCLUSIONS: HCC risk is associated with sequence
      variation in the EnhII/BCP regions of HBV, and persistence of at-risk sequence
      variants is critical for HCC development.

PMID- 17502345
TI  - To clean or not to clean: effect on contamination rates in midstream urine
      collections in toilet-trained children.
AB  - OBJECTIVE: Urinary tract infection is one of the most common bacterial infections
      among children. Difficulty in specimen collection and interpretation of
      inadequately collected specimens may contribute to misdiagnosis of urinary tract
      infection. Our objective was to assess the effect of perineal/genital cleaning on
      bacterial contamination rates of midstream urine collections in toilet-trained
      children. METHODS: We conducted a randomized trial in toilet-trained children who
      presented to a tertiary care pediatric emergency department between November 1,
      2004, and October 1, 2005. All toilet-trained children who were between the ages
      of 2 and 18 years and had a midstream urine sample requested were eligible. Those
      whose parents consented were cluster-randomized by week to either cleaning or not
      cleaning the perineum with soap. The risk for a contaminated urine culture
      (defined as growth of < 10(8) colony-forming units per liter [< 10(5) colony
      forming units per milliliter] of a single organism or a mix of > or = 2
      organisms) and the risk for a positive urinalysis (defined as a positive
      leukocyte esterase and/or nitrites on dipstick or > or = 5 white blood cells per
      high-powered field on a standard microscopic examination) were analyzed by
      intention to treat. RESULTS: A total of 350 children were enrolled. The rate of
      contamination in the cleaning group was 14 (7.8%) of 179 vs 41 (23.9%) of 171 in
      the noncleaning group. Children who were randomly assigned to cleaning were less
      likely to have a positive urinalysis (37 of 179 [20.6%]) than those in the
      noncleaning group (63 of 171 [36.8%]). CONCLUSIONS: Urine contamination rates are
      higher in midstream urine that is collected from toilet-trained children when
      obtained without perineal/genital cleaning. Cleaning may reduce the risk for
      returning for repeat cultures and for receiving unnecessary antibiotic treatment
      and investigations.

PMID- 17502346
TI  - Perinatal circulating visfatin levels in intrauterine growth restriction.
AB  - OBJECTIVE: The objective of this study was to investigate possible alterations in
      circulating levels of the adipocytokine visfatin in intrauterine growth
      restricted and normal pregnancies, given that these groups differ considerably in
      fetal nutrition, body fat mass, and metabolic/endocrine mechanisms. METHODS:
      Serum visfatin levels were prospectively measured by enzyme immunoassay in 40
      mothers and their 40 singleton term fetuses and neonates on postnatal days 1 and
      4. Twenty neonates had intrauterine growth restriction (birth weight < or = 3rd
      customized centile, adjusted for parameters that influence growth potential), and
      20 were appropriate for gestational age. RESULTS: Circulating maternal visfatin
      levels were significantly elevated in pregnancies with intrauterine growth
      restriction compared with control pregnancies with appropriate-for-gestational
      age infants and negatively correlated with customized centiles in the group with
      intrauterine growth restriction. Postnatal day-1 and -4 visfatin levels were
      significantly higher in neonates with intrauterine growth restriction compared
      with neonates who were appropriate for gestational age. Postnatal-day-1
      prefeeding insulin levels were significantly lower in neonates with intrauterine
      growth restriction. CONCLUSIONS: Pathologic conditions in pregnancy that lead to
      intrauterine growth restriction could be responsible for elevated maternal
      visfatin levels. Higher visfatin levels in neonates with intrauterine growth
      restriction may serve as an early marker with prognostic value for later
      development of insulin resistance or type 2 diabetes, whereas lower insulin
      levels may indicate reduced beta-cell mass and/or impaired beta-cell function.

PMID- 17502347
TI  - Comparison of the safety and immunogenicity of a refrigerator-stable versus a
      frozen formulation of ProQuad (measles, mumps, rubella, and varicella virus
      vaccine live).
AB  - OBJECTIVE: A refrigerator-stable formulation of ProQuad has been developed to
      expand the utility of ProQuad to areas in which maintenance of a frozen cold
      chain (-15 degrees C or colder) during storage and transport may not be feasible.
      The objective of this study was to demonstrate that the immunogenicity and safety
      profiles of a refrigerator-stable formulation of ProQuad are similar to the
      recently licensed frozen formulation. METHODS: In this double-blind, randomized,
      multicenter study, healthy 12- to 23-month-old children with negative vaccination
      and clinical histories for measles, mumps, rubella, varicella, and zoster were
      vaccinated with either the refrigerator-stable formulation of ProQuad (N = 1006)
      or the frozen formulation of ProQuad (N = 513). Patients were followed for 42
      days after vaccination for adverse experiences. Immunogenicity was evaluated 6
      weeks after vaccination. RESULTS: The refrigerator-stable formulation of ProQuad
      was generally well tolerated. The incidence of adverse experiences was similar
      between groups. No vaccine-related serious adverse experiences were reported. For
      both groups, the response rate was > or = 97.7% for measles, mumps, and rubella,
      and the percentage of patients with a varicella zoster virus antibody titer of >
      or = 5 U/mL glycoprotein antigen-based enzyme-linked immunosorbent assay after
      vaccination was > or = 88.8%. The geometric mean titers for all antigens were
      numerically slightly higher in patients who received the refrigerator-stable
      formulation. CONCLUSIONS: The refrigerator-stable formulation of ProQuad is
      generally well tolerated, highly immunogenic, and noninferior in terms of
      postvaccination antibody responses. This refrigerator-stable formulation may
      improve ease of vaccine administration, increase use of the vaccine throughout
      the world because of its improved storage conditions, and replace the frozen
      formulation of ProQuad or any dose of M-M-RII and Varivax in routine practice.

PMID- 17502348
TI  - CD3 and immunoglobulin G Fc receptor regulate cerebellar functions.
AB  - The immune and nervous systems display considerable overlap in their molecular
      repertoire. Molecules originally shown to be critical for immune responses also
      serve neuronal functions that include normal brain development, neuronal
      differentiation, synaptic plasticity, and behavior. We show here that
      FcgammaRIIB, a low-affinity immunoglobulin G Fc receptor, and CD3 are involved in
      cerebellar functions. Although membranous CD3 and FcgammaRIIB are crucial
      regulators on different cells in the immune system, both CD3epsilon and
      FcgammaRIIB are expressed on Purkinje cells in the cerebellum. Both CD3epsilon
      deficient mice and FcgammaRIIB-deficient mice showed an impaired development of
      Purkinje neurons. In the adult, rotarod performance of these mutant mice was
      impaired at high speed. In the two knockout mice, enhanced paired-pulse
      facilitation of parallel fiber-Purkinje cell synapses was shared. These results
      indicate that diverse immune molecules play critical roles in the functional
      establishment in the cerebellum.

PMID- 17502349
TI  - Differential regulation of NF-kappaB by elongation factors is determined by core
      promoter type.
AB  - NF-kappaB transcription factors activate genes important for immune response,
      inflammation, and cell survival. P-TEFb and DSIF, which are positive and negative
      transcription elongation factors, respectively, both regulate NF-kappaB-induced
      transcription, but the mechanism underlying their recruitment to NF-kappaB target
      genes is unknown. We show here that upon induction of NF-kappaB, a subset of
      target genes is regulated differentially by either P-TEFb or DSIF. The regulation
      of these genes and their occupancy by these elongation factors are dependent on
      the NF-kappaB enhancer and the core promoter type. Converting a TATA-less
      promoter to a TATA promoter switches the regulation of NF-kappaB from DSIF to P
      TEFb. Accumulation or displacement of DSIF and P-TEFb is dictated by the
      formation of distinct initiation complexes (TFIID dependent or independent) on
      the two types of core promoter. The underlying mechanism for the dissociation of
      DSIF from TATA promoters upon NF-kappaB activation involves the phosphorylation
      of RNA polymerase II by P-TEFb. The results highlight a regulatory link between
      the initiation and the elongation phases of the transcription reaction and
      broaden our comprehension of the NF-kappaB pathway.

PMID- 17502350
TI  - Integration of estrogen and Wnt signaling circuits by the polycomb group protein
      EZH2 in breast cancer cells.
AB  - Essential for embryonic development, the polycomb group protein enhancer of zeste
      homolog 2 (EZH2) is overexpressed in breast and prostate cancers and is
      implicated in the growth and aggression of the tumors. The tumorigenic mechanism
      underlying EZH2 overexpression is largely unknown. It is believed that EZH2
      exerts its biological activity as a transcription repressor. However, we report
      here that EZH2 functions in gene transcriptional activation in breast cancer
      cells. We show that EZH2 transactivates genes that are commonly targeted by
      estrogen and Wnt signaling pathways. We demonstrated that EZH2 physically
      interacts directly with estrogen receptor alpha and beta-catenin, thus connecting
      the estrogen and Wnt signaling circuitries, functionally enhances gene
      transactivation by estrogen and Wnt pathways, and phenotypically promotes cell
      cycle progression. In addition, we identified the transactivation activity of
      EZH2 in its two N-terminal domains and demonstrated that these structures serve
      as platforms to connect transcription factors and the Mediator complex. Our
      experiments indicated that EZH2 is a dual function transcription regulator with a
      dynamic activity, and we provide a mechanism for EZH2 in tumorigenesis.

PMID- 17502351
TI  - Cooperation between p27 and p107 during endochondral ossification suggests a
      genetic pathway controlled by p27 and p130.
AB  - Pocket proteins and cyclin-dependent kinase (CDK) inhibitors negatively regulate
      cell proliferation and can promote differentiation. However, which members of
      these gene families, which cell type they interact in, and what they do to
      promote differentiation in that cell type during mouse development are largely
      unknown. To identify the cell types in which p107 and p27 interact, we generated
      compound mutant mice. These mice were null for p107 and had a deletion in p27
      that prevented its binding to cyclin-CDK complexes. Although a fraction of these
      animals survived into adulthood and looked similar to single p27 mutant mice, a
      larger number of animals died at birth or within a few weeks thereafter. These
      animals displayed defects in chondrocyte maturation and endochondral bone
      formation. Proliferation of chondrocytes was increased, and ectopic ossification
      was observed. Uncommitted mouse embryo fibroblasts could be induced into the
      chondrocytic lineage ex vivo, but these cells failed to mature normally. These
      results demonstrate that p27 carries out overlapping functions with p107 in
      controlling cell cycle exit during chondrocyte maturation. The phenotypic
      similarities between p107(-/-) p27(D51/D51) and p107(-/-) p130(-/-) mice and the
      cells derived from them suggest that p27 and p130 act in an analogous pathway
      during chondrocyte maturation.

PMID- 17502353
TI  - Phosphorylation of Bcl10 negatively regulates T-cell receptor-mediated NF-kappaB
      activation.
AB  - Bcl10 (B-cell lymphoma 10) is an adaptor protein comprised of an N-terminal
      caspase recruitment domain and a C-terminal serine/threonine-rich domain. Bcl10
      plays a critical role in antigen receptor-mediated NF-kappaB activation and
      lymphocyte development and functions. Our current study has discovered that T
      cell activation induced monophosphorylation and biphosphorylation of Bcl10 and
      has identified S138 within Bcl10 as one of the T-cell receptor-induced
      phosphorylation sites. Alteration of S138 to an alanine residue impaired T-cell
      activation-induced ubiquitination and subsequent degradation of Bcl10, ultimately
      resulting in prolongation of TCR-mediated NF-kappaB activation and enhancement of
      interleukin-2 production. Taken together, our findings demonstrate that
      phosphorylation of Bcl10 at S138 down-regulates Bcl10 protein levels and thus
      negatively regulates T-cell receptor-mediated NF-kappaB activation.

PMID- 17502352
TI  - Transcriptional repressor erf determines extraembryonic ectoderm differentiation.
AB  - Extraembryonic ectoderm differentiation and chorioallantoic attachment are
      fibroblast growth factor (FGF)- and transforming growth factor beta-regulated
      processes that are the first steps in the development of the placenta labyrinth
      and the establishment of the fetal-maternal circulation in the developing embryo.
      Only a small number of genes have been demonstrated to be important in
      trophoblast stem cell differentiation. Erf is a ubiquitously expressed Erk
      regulated, ets domain transcriptional repressor expressed throughout embryonic
      development and adulthood. However, in the developing placenta, after 7.5 days
      postcoitum (dpc) its expression is restricted to the extraembryonic ectoderm, and
      its expression is restricted after 9.5 dpc in a subpopulation of labyrinth cells.
      Homozygous deletion of Erf in mice leads to a block of chorionic cell
      differentiation before chorioallantoic attachment, resulting in a persisting
      chorion layer, a persisting ectoplacental cone cavity, failure of chorioallantoic
      attachment, and absence of labyrinth. These defects result in embryo death by
      10.5 dpc. Trophoblast stem cell lines derived from Erf(dl1/dl1) knockout
      blastocysts exhibit delayed differentiation and decreased expression of
      spongiotrophoblast markers, consistent with the persisting chorion layer, the
      expanded giant cell layer, and the diminished spongiotrophoblast layer observed
      in vivo. Our data suggest that attenuation of FGF/Erk signaling and consecutive
      Erf nuclear localization and function is required for extraembryonic ectoderm
      differentiation, ectoplacental cone cavity closure, and chorioallantoic
      attachment.

PMID- 17502354
TI  - Type I interferons are involved in the development of  ultraviolet B-induced
      inflammatory skin lesions in  systemic lupus erythaematosus patients.
AB  - OBJECTIVE: To investigate the involvement of type I interferons and endothelial
      cell adhesion molecules in the development of ultraviolet B (UVB)-induced
      systemic lupus erythaematosus (SLE) skin lesions. METHODS: A total of 19 SLE
      patients and 13 controls were irradiated with two minimal erythaemal doses(MED)
      of UVB. Subsequently, skin biopsies were analysed (immuno) histologically over 10
      days, for expression of IFNalpha-induced MxA, numbers of plasmacytoid dendritic
      cells (pDC), and expression of endothelial cell adhesion molecules, namely E
      selectin, ICAM-1, and L-selectin ligand. Additionally, MxA expression was
      compared to its expression in nine established cutaneous lupus
      erythaematosus(CLE) lesions of SLE patients. RESULTS: Before irradiation IFNalpha
      induced MxA was expressed at significantly higher levels in non-lesional skin of
      SLE patients compared to healthy controls. In patients developing infiltrates
      upon UVB irradiation, MxA expression increased further, reaching expression
      levels similar to or exceeding levels in CLE-skin lesions. In these patients, MxA
      expression was sustained up to day 10, in contrast to patients not developing
      infiltrates in whom expression decreased. No noteworthy numbers of plasmacytoid
      dendritic cells (pDC) were detected in nonirradiated skin or at any time after
      UVB exposure in SLE patients or controls. MxA expression correlated with influx
      of T-cells and monocytes/macrophages, and with expression of E-selectin and ICAM
      1. CONCLUSION: Development of UVB-induced SLE skin lesions involves a skewing
      towards production of Th1-associated cytokines, such as IFNalpha. In turn, this
      may lead to up-regulation of E-selectin and ICAM-1 resulting in recruitment of T
      cells and macrophages.

PMID- 17502356
TI  - Bone mineral density in patients with hand osteoarthritis compared to population
      controls and patients with rheumatoid arthritis.
AB  - OBJECTIVES: Several studies have revealed increased bone mineral density (BMD) in
      patients with knee or hip osteoarthritis, but few studies have addressed this
      issue in hand osteoarthritis (HOA). The aims of this study were to compare BMD
      levels and frequency of osteoporosis between female patients with HOA, rheumatoid
      arthritis (RA) and controls aged 50-70 years, and to explore possible
      relationships between BMD and disease characteristics in patients with HOA.
      METHODS: 190 HOA and 194 RA patients were recruited from the respective disease
      registers in Oslo, and 122 controls were selected from the population register of
      Oslo. All participants underwent BMD measurements of femoral neck, total hip and
      lumbar spine (dual-energy x ray absorptiometry), interview, clinical joint
      examination and completed self-reported questionnaires. RESULTS: Age-, weight-
      and height-adjusted BMD values were significantly higher in HOA versus RA and
      controls, the latter only significant for femoral neck and lumbar spine. The
      frequency of osteoporosis was not significantly different between HOA and
      controls, but significantly lower in HOA versus RA. Adjusted BMD values did not
      differ between HOA patients with and without knee OA, and significant
      associations between BMD levels and symptom duration or disease measures were not
      observed. CONCLUSION: HOA patients have a higher BMD than population-based
      controls, and this seems not to be limited to patients with involvement of larger
      joints. The lack of correlation between BMD and disease duration or severity does
      not support the hypothesis that higher BMD is a consequence of the disease
      itself.

PMID- 17502357
TI  - Attitudes of United Kingdom rheumatologists to musculoskeletal ultrasound
      practice and training.
AB  - OBJECTIVES: This study was performed to describe what clinical rheumatologists
      currently use musculoskeletal ultrasound (MSUS) for, how they are currently
      training and is the first study to survey rheumatologists to determine their
      preferences for MSUS training implementation. METHODS: 250 questionnaires were
      distributed at the British Society of Rheumatology Annual General Meeting (BSR
      AGM), 2005. RESULTS: 126 (50%) of questionnaires were completed by UK
      rheumatologists and were analysed. 117 (93%) of the respondents use MSUS imaging
      for patient management, with 41 (33%) indicating they perform MSUS themselves.
      Only two (2%) performed MSUS for >5 years. Rheumatologists use MSUS to image all
      peripheral joints-particularly the hands and feet-to assess joint and soft tissue
      inflammation and to guide joint injections. Lack of training in MSUS was the
      principal reason for not performing MSUS. Respondents expressed a preference for
      future training to be via a programme of regular sessions, with training
      delivered by either consultant radiologists or rheumatologists. Mentoring was the
      educational tool and assessment method of choice. CONCLUSIONS: The majority of
      respondents use MSUS in the management of their patients, with a third performing
      MSUS themselves. The report indicates rheumatologists' preferences on how
      training should be delivered in the future.

PMID- 17502358
TI  - Cigarette smoking significantly increases basal  metabolic rate in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: Basal metabolic rate (BMR) is the most important indicator of human
      metabolism and its abnormalities have been linked to undesirable health outcomes.
      Cigarette smoking associates with increased BMR in healthy individuals; it is
      also related with worse disease outcomes in patients with rheumatoid
      arthritis(RA), in whom BMR is high due to hypercatabolism caused by systemic
      inflammation. We aimed to investigate whether smokers with RA demonstrated higher
      BMR levels than their non-smoking counterparts. METHODS: A total of 53 patients
      with RA (36 female, 17 male, 20 current smokers) were assessed for: BMR(indirect
      calorimetry), anthropometrical data, fat-free mass (bioelectrical impedance),
      physical function (health assessment questionnaire; HAQ) and disease
      activity(disease activity score DAS28 and C reactive protein). RESULTS: RA
      smokers and non-smokers were not significantly different for age, height, weight,
      body mass index and fat-free mass. Compared to non-smokers,smokers with RA
      demonstrated significantly higher BMR (mean (SD) 1513.9 (263.3) vs 1718.1 (209.2)
      kcal/day; p,0.001) and worse HAQ (1.0 (0.8) vs 1.7 (0.8); p=0.01). The BMR
      difference was significantly predicted by the interaction smoking/gender
      (p=0.04). BMR was incrementally higher in light, moderate and heavy smokers
      (p=0.018), and correlated with the daily number of cigarettes smoked (r=0.68,
      p=0.04). CONCLUSION: Current cigarette smoking further increases BMR in patients
      with RA and has a negative impact on patients self-reported functional status.
      Education regarding smoking cessation is needed for the RA population.

PMID- 17502359
TI  - Low-dose glucocorticoid therapy decreases risk for treatment-limiting infusion
      reaction to infliximab in patients with rheumatoid arthritis.
AB  - BACKGROUND AND OBJECTIVE: Treatment-limiting infusion reactions to infliximab
      have not been fully explained in rheumatoid arthritis patients. Our main
      objective is to investigate the role of daily oral glucocorticoids use on such
      reactions. METHOD: Forty-three patients with immediate-type infusion reactions
      were identified in a large registry-based cohort. These patients were then
      compared with the entire cohort (n = 639) and, in a separate analysis, to a
      nested matched control group (n = 43). The following base-line variables were
      compared: use of oral glucocorticoids, health-assessment questionnaire, 28-joint
      count-based disease activity score, duration of disease and number of failed
      disease-modifying antirheumatic drugs. RESULTS: The proportion of infusions
      associated with infusion reactions decreased significantly during the study
      period (p = 0.0024). Fifty per cent of the patients in the cohort were treated
      with daily low-dose glucocorticoids at baseline. 15/326 (4.6%) patients had an
      infusion reaction as compared with 28/324 (8.6%) of patients without
      glucocorticoid treatment (p = 0.057). In the matched comparison, 15/43 (35%) of
      the cases were on low-dose glucocorticoids as compared with 27/43 (64%) of the
      controls (p = 0.017). The use of low-dose glucocorticoids was associated with a
      significantly lower risk for a treatment-limiting infusion reactions in a Kaplan
      Meier analysis (p = 0.04). The number needed to treat to prevent a treatment
      limiting infusion reaction was 25 (95% CI: 13 to 527) in the cohort. CONCLUSION:
      The use of daily low-dose glucocorticoids is associated with a lower risk for
      treatment-limiting infusion reactions to infliximab. Overall, treatment-limiting
      infusion reactions have become significantly less common during the past 5 years.

PMID- 17502360
TI  - Cellular targets of interleukin-18 in rheumatoid arthritis.
AB  - Recent data are presented which indicate a critical role for interleukin (IL)-18
      in rheumatoid arthritis (RA). The T cells and macrophages invading the synovium
      or in the synovial fluid are the chief cellular targets of IL-18 in RA.
      Neutrophils, dendritic cells and endothelial cells may also be cellular mediators
      of IL-18. The direct effect of IL-18 on fibroblast-like synoviocytes or
      chondrocytes may not be essential or important. In RA, IL-18, which is mainly
      produced by macrophages, activates T cells and macrophages to produce
      proinflammatory cytokines, chemokines, adhesion molecules and RANKL which, in
      turn, perpetuate chronic inflammation and induce bone and cartilage destruction.

PMID- 17502362
TI  - Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic
      chondrocytes: possible molecular target for osteoarthritis therapeutic
      intervention.
AB  - OBJECTIVE: To investigate whether epigenetic mechanisms can regulate leptin's
      expression and affect its downstream targets as metalloproteinases 3,9,13 in
      osteoarthritic chondrocytes. METHODS: DNA methylation in leptin promoter was
      measured by DNA bisulfite sequencing, and mRNA expression levels were measured by
      real-time quantitative PCR in osteoarthritic as well as in normal cartilage.
      Osteoarthritic articular cartilage samples were obtained from two distinct
      locations of the knee (n = 15); from the main defective area of maximum load
      (advanced osteoarthritis (OA)) and from adjacent macroscopically intact regions
      (minimal OA). Using small interference RNA, we tested if leptin downregulation
      would affect matrix metalloproteinase (MMP)-13 activity. We also evaluated the
      effect of the demethylating agent, 5'-Aza-2-deoxycytidine (AZA) and of the
      histone deacetylase inhibitor trichostatin A (TSA) on leptin expression in
      chondrocyte cultures. Furthermore, we performed chromatin immunoprecipitation in
      leptin's promoter area. RESULTS: We found a correlation between leptin expression
      and DNA methylation and also that leptin controls MMP-13 activity in
      chondrocytes. Leptin's downregulation with small interference RNA inhibited MMP
      13 expression dramatically. After 5-AZA application in normal chondrocytes,
      leptin's methylation was decreased, while its expression was upregulated, and MMP
      13 was activated. Furthermore, TSA application in normal chondrocyte cultures
      increased leptin's expression. Also, chromatin immunoprecipitation in leptin's
      promoter after TSA treatment revealed that histone H3 lysines 9 and 14 were
      acetylated. CONCLUSION: We found that epigenetic mechanisms regulate leptin's
      expression in chondrocytes affecting its downstream target MMP-13. Small
      interference RNA against leptin deactivated directly MMP-13, which was
      upregulated after leptin's epigenetic reactivation, raising the issue of leptin's
      therapeutic potential for osteoarthritis.

PMID- 17502363
TI  - Gelatinase expression and proteolytic activity in giant-cell arteritis.
AB  - OBJECTIVES: Gelatinases (MMP2 and MMP9) are expressed in giant-cell arteritis
      (GCA) and are thought to play a role in vessel disruption. However, their
      activation status and enzymatic activity have not been evaluated. Our aim was to
      investigate the distribution and proteolytic activity of gelatinases in GCA
      lesions at different stages. METHODS: Expression of MMP2, MMP9, MMP2-activator
      MMP14 and their natural inhibitors TIMP1 and TIMP2 was determined by real-time
      PCR and immunohistochemistry in temporal artery sections from 46 patients and 12
      controls. MMP activation status and enzymatic activity were assessed by gelatin
      and film in situ zymography. RESULTS: Vascular smooth muscle cells from normal
      specimens constitutively expressed pro-MMP2 and its inhibitor TIMP2 with no
      resulting proteolytic activity. In GCA MMP2, MMP9 and MMP14 were strongly
      expressed in their active form by infiltrating leucocytes. Inflamed arteries also
      expressed TIMP1 and TIMP2. However, the MMP9/TIMP1 and MMP2/TIMP2 ratios were
      higher in patients compared with controls, indicating an increased proteolytic
      balance in GCA which was confirmed by in situ zymography. Maximal gelatinase
      expression and activity occurred at the granulomatous areas surrounding the
      internal elastic lamina (IEL). Myointimal cells also expressed MMPs and exhibited
      proteolytic activity, suggesting a role for gelatinases in vascular remodelling
      and repair. CONCLUSIONS: GCA lesions show intense expression of gelatinases.
      Activators and inhibitors are regulated to yield enhanced gelatinase activation
      and proteolytic activity. Distribution of expression and proteolytic activity
      suggests that gelatinases have a major role not only in the progression of
      inflammatory infiltrates and vessel destruction but also in vessel repair.

PMID- 17502364
TI  - Development and validation of a scale for mouth handicap in systemic sclerosis:
      the Mouth Handicap in Systemic Sclerosis scale.
AB  - OBJECTIVE: To develop and assess the reliability and construct validity of a
      scale assessing disability involving the mouth in systemic sclerosis (SSc).
      METHODS: We generated a 34-item provisional scale from mailed responses of
      patients (n = 74), expert consensus (n = 10) and literature analysis. A total of
      71 other SSc patients were recruited. The test-retest reliability was assessed
      using the intraclass coefficient correlation and divergent validity using the
      Spearman correlation coefficient. Factor analysis followed by varimax rotation
      was performed to assess the factorial structure of the scale. RESULTS: The item
      reduction process retained 12 items with 5 levels of answers (total score range 0
      48). The mean total score of the scale was 20.3 (SD 9.7). The test-retest
      reliability was 0.96. Divergent validity was confirmed for global disability
      (Health Assessment Questionnaire (HAQ), r = 0.33), hand function (Cochin Hand
      Function Scale, r = 0.37), inter-incisor distance (r = -0.34), handicap (McMaster
      Toronto Arthritis questionnaire (MACTAR), r = 0.24), depression (Hospital Anxiety
      and Depression (HAD); HADd, r = 0.26) and anxiety (HADa, r = 0.17). Factor
      analysis extracted 3 factors with eigenvalues of 4.26, 1.76 and 1.47, explaining
      63% of the variance. These 3 factors could be clinically characterised. The first
      factor (5 items) represents handicap induced by the reduction in mouth opening,
      the second (5 items) handicap induced by sicca syndrome and the third (2 items)
      aesthetic concerns. CONCLUSION: We propose a new scale, the Mouth Handicap in
      Systemic Sclerosis (MHISS) scale, which has excellent reliability and good
      construct validity, and assesses specifically disability involving the mouth in
      patients with SSc.

PMID- 17502367
TI  - JAK-STAT signaling: from interferons to cytokines.

PMID- 17502368
TI  - Type I interferon receptors: biochemistry and biological functions.

PMID- 17502369
TI  - The interferons: 50 years after their discovery, there is much more to learn.
AB  - The interferons (IFNs) and their receptors represent a subset of the class 2
      alpha-helical cytokines that have been in chordates for millions of years. This
      brief review focuses on the discovery and purification of interferons, cloning of
      human IFN-alpha and IFN-beta, interferon receptors, activities and therapeutic
      uses of interferons, and the side effects of interferons.

PMID- 17502370
TI  - The interferon regulatory factor family in host defense: mechanism of action.
AB  - Transcription factors of the interferon regulatory factor (IRF) family commands
      the entire type I interferon (IFN) system from induction of IFNs to diverse IFN
      responses, thereby providing a principal basis for host resistance against
      pathogens. However, the family has various additional roles. Regulating the
      development of the immune system, IRFs shape the establishment and execution of
      innate and adaptive immunity. IRFs also regulate growth and differentiation of
      many cell types, thus playing a role in leukemia and other cancers. In addition,
      evidence indicates that IRFs confer antiviral mechanisms not directly ascribed to
      the IFN system. This review deals with the diverse roles of IRFs in host defense
      and discusses the molecular mechanisms by which they regulate target gene
      transcription.

PMID- 17502371
TI  - Inducible hyaluronan production reveals differential effects on prostate tumor
      cell growth and tumor angiogenesis.
AB  - Prostate cancer progression can be predicted in human tumor biopsies by abundant
      hyaluronan (HA) and its processing enzyme, the hyaluronidase HYAL1. Accumulation
      of HA is dictated by the balance between expression levels of HA synthases, the
      enzymes that produce HA polymers, and hyaluronidases, which process polymers to
      oligosaccharides. Aggressive prostate tumor cells express 20-fold higher levels
      of the hyaluronan synthase HAS3, but the mechanistic relevance of this
      correlation has not been determined. We stably overexpressed HAS3 in prostate
      tumor cells. Adhesion to extracellular matrix and cellular growth kinetics in
      vitro were significantly reduced. Slow growth in culture was restored either by
      exogenous addition of hyaluronidase or by stable HYAL1 coexpression. Coexpression
      did not improve comparably slow growth in mice, however, suggesting that excess
      hyaluronan production by HAS3 may alter the balance required for induced tumor
      growth. To address this, we used a tetracycline-inducible HAS3 expression system
      in which hyaluronan production could be experimentally controlled. Adjusting
      temporal parameters of hyaluronan production directly affected growth rate of the
      cells. Relief from growth suppression in vitro but not in vivo by enzymatic
      removal of HA effectively uncoupled the respective roles of hyaluronan in growth
      and angiogenesis, suggesting that growth mediation is less critical to
      establishment of the tumor than early vascular development. Collectively results
      also imply that HA processing by elevated HYAL1 expression in invasive prostate
      cancer is a requirement for progression.

PMID- 17502372
TI  - Chain initiation in the leinamycin-producing hybrid nonribosomal
      peptide/polyketide synthetase from Streptomyces atroolivaceus S-140. Discrete,
      monofunctional adenylation enzyme and peptidyl carrier protein that directly load
      D-alanine.
AB  - Nonribosomal peptide natural products are biosynthesized from amino acid
      precursors by nonribosomal peptide synthetases (NRPSs), which are organized into
      modules. For a typical NRPS initiation module, an adenylation (A) domain
      activates an amino acid and installs it onto a peptidyl carrier protein (PCP)
      domain as a thioester; an elongation module, which has a condensation (C) domain
      located between every consecutive pair of A and PCP domains, catalyzes the
      formation of the peptide bond between the upstream aminoacyl/peptidyl-S-PCP and
      the free amino group of the downstream aminoacyl-S-PCP. D-amino acid constituents
      in peptide natural products usually arise from the L-enantiomers through the
      action of integral epimerization (E) domains of an NRPS. The biosynthetic gene
      cluster for leinamycin, a hybrid nonribosomal peptide/polyketide containing a D
      alanine moiety, does not encode a typical NRPS initiation module with the
      expected A-PCP-E domains; instead, it has only an A protein (LnmQ) and a PCP
      (LnmP), both of which are encoded by separate genes. Here we show the results of
      biochemical experiments as follows: (i) we demonstrate that LnmQ directly
      activates D-alanine as D-alaninyl-AMP and installs it onto LnmP to generate a D
      alaninyl-S-PCP intermediate; (ii) we confirm that aminoacylation of LnmP by LnmQ
      in trans is the result of specific communication between the separate A and PCP
      proteins; and (iii) we reveal that leinamycin production can be improved by
      supplementation of exogenous D-alanine in the fermentation broth of Streptomyces
      atroolivaceous S-140. These findings unveil an unprecedented NRPS initiation
      module structure that is characterized by a discrete D-alanine-specific A protein
      and a PCP.

PMID- 17502373
TI  - Fission yeast Rnf4 homologs are required for DNA repair.
AB  - We describe two RING finger proteins in the fission yeast Schizosaccharomyces
      pombe, Rfp1 and Rfp2. We show that these proteins function redundantly in DNA
      repair. Rfp1 was isolated as a Chk1-interacting protein in a two-hybrid screen
      and has high amino acid sequence similarity to Rfp2. Deletion of either gene does
      not cause a phenotype, but a double deletion (rfp1Deltarfp2Delta) showed poor
      viability and defects in cell cycle progression. These cells are also sensitive
      to DNA-damaging agents, although they maintained normal checkpoint signaling to
      Chk1. Rfp1 and Rfp2 are most closely related to human Rnf4, and we showed that
      Rnf4 can substitute functionally for Rfp1 and/or Rfp2. The double mutants also
      showed significantly increased levels of protein SUMOylation, and we identified
      an S. pombe Ulp2/Smt4 homolog that, when overexpressed, reduced SUMO levels and
      suppressed the DNA damage sensitivity of rfp1Delta rfp2Delta cells.

PMID- 17502374
TI  - Regulation of mammalian protein O-mannosylation: preferential amino acid sequence
      for O-mannose modification.
AB  - O-mannosyl glycans are important in muscle and brain development. Protein O
      mannosyltransferase (POMT) catalyzes the initial step of O-mannosyl glycan
      biosynthesis. To understand which serine (Ser) and threonine (Thr) residues POMT
      recognizes for mannosylation, we prepared a series of synthetic peptides based on
      a mucin-like domain in alpha-dystroglycan (alpha-DG), one of the best known O
      mannosylated proteins in mammals. In alpha-DG, the mucin-like domain spans amino
      acid residues 316 to 489. Two similar peptide sequences, corresponding to
      residues 401-420 and 336-355, respectively, were strongly mannosylated by POMT,
      whereas other peptides from alpha-DG and peptides of various mucin tandem repeat
      regions were poorly mannosylated. Peptides 401-420 and 336-355 contained four and
      six Ser and Thr residues, respectively. Substitution of Ala residues for the Ser
      or Thr residues showed that Thr-414 of peptide 401-420 and Thr-351 of peptide 336
      355 were prominently modified by O-mannosylation. Matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry and Edman degradation
      analysis of the mannosylated peptide 401-420 indicated that Thr-414 was the Thr
      residue that was most prominently modified by O-mannosylation and that O
      mannosylation occurred sequentially rather than at random. Based on these
      results, we propose a preferred amino acid sequence for mammalian O-mannose
      modification.

PMID- 17502375
TI  - Cloning and characterization of a functional human gamma-aminobutyric acid (GABA)
      transporter, human GAT-2.
AB  - Plasma membrane gamma-aminobutyric acid (GABA) transporters act to terminate GABA
      neurotransmission in the mammalian brain. Intriguingly four distinct GABA
      transporters have been cloned from rat and mouse, whereas only three functional
      homologs of these transporters have been cloned from human. The aim of this study
      therefore was to search for this fourth missing human transporter. Using a
      bioinformatics approach, we successfully identified and cloned the full-length
      cDNA of a so far uncharacterized human GABA transporter (GAT). The predicted
      protein displays high sequence similarity to rat GAT-2 and mouse GAT3, and in
      accordance with the nomenclature for rat GABA transporters, we therefore refer to
      the transporter as human GAT-2. We used electrophysiological and cell-based
      methods to demonstrate that this protein is a functional transporter of GABA. The
      transport was saturable and dependent on both Na(+) and Cl(-). Pharmacologically
      the transporter is distinct from the other human GABA transporters and similar to
      rat GAT-2 and mouse GAT3 with high sensitivity toward GABA and beta-alanine.
      Furthermore the GABA transport inhibitor (S)-SNAP-5114 displayed some inhibitory
      activity at the transporter. Expression analysis by reverse transcription-PCR
      showed that GAT-2 mRNA is present in human brain, kidney, lung, and testis. The
      finding of the human GAT-2 demonstrates for the first time that the four plasma
      membrane GABA transporters identified in several mammalian species are all
      conserved in human. Furthermore the availability of human GAT-2 enables the use
      of all human clones of the GABA transporters in drug development programs and
      functional characterization of novel inhibitors of GABA transport.

PMID- 17502376
TI  - SPFH2 mediates the endoplasmic reticulum-associated degradation of inositol 1,4,5
      trisphosphate receptors and other substrates in mammalian cells.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) receptors are endoplasmic reticulum (ER)
      membrane calcium channels that, upon activation, become substrates for the ER
      associated degradation (ERAD) pathway. Although it is clear that IP(3) receptors
      are polyubiquitinated upon activation and are transferred to the proteasome by a
      p97-based complex, currently nothing is known about the proteins that initially
      select activated IP(3) receptors for ERAD. Here, we sought to identify novel
      proteins that associate with and mediate the ERAD of endogenous activated IP(3)
      receptors. SPFH2, an uncharacterized SPFH domain-containing protein, rapidly
      associated with IP(3) receptors in a manner that preceded significant
      polyubiquitination and the association of p97 and related proteins. SPFH2 was
      found to be an ER membrane protein largely residing within the ER lumen and in
      resting and stimulated cells was linked to ERAD pathway components, apparently
      via endogenous substrates undergoing degradation. Suppression of SPFH2 expression
      by RNA interference markedly inhibited IP(3) receptor polyubiquitination and
      degradation and the processing of other ERAD substrates. Overall, these studies
      identify SPFH2 as a key ERAD pathway component and suggest that it may act as a
      substrate recognition factor.

PMID- 17502377
TI  - Direct versus limited-step reconstitution reveals key features of an RNA hairpin
      stabilized paused transcription complex.
AB  - We have identified minimal nucleic acid scaffolds capable of reconstituting
      hairpin-stabilized paused transcription complexes when incubated with RNAP either
      directly or in a limited step reconstitution assay. Direct reconstitution was
      achieved using a 29-nucleotide (nt) RNA whose 3'-proximal 9-10 nt pair to
      template DNA within an 11-nt noncomplementary bubble of a 39-bp duplex DNA; the
      5'-proximal 18 nt of RNA forms the his pause RNA hairpin. Limited-step
      reconstitution was achieved on the same DNAs using a 27-nt RNA that can be 3'
      labeled during reconstitution and then extended 2 nt past the pause site to assay
      transcriptional pausing. Paused complexes formed by either method recapitulated
      key features of a promoter-initiated, hairpin-stabilized paused complex,
      including a slow rate of pause escape, resistance to transcript cleavage and
      pyrophosphorolysis, and enhancement of pausing by the elongation factor NusA.
      These findings establish that RNA upstream from the pause hairpin and
      pyrophosphate are not essential for pausing and for NusA action. Reconstitution
      of the his paused transcription complex provides a valuable tool for future
      studies of protein-nucleic interactions involved in transcriptional pausing.

PMID- 17502378
TI  - The 1.8 A crystal structure of PA2412, an MbtH-like protein from the pyoverdine
      cluster of Pseudomonas aeruginosa.
AB  - Many bacteria use nonribosomal peptide synthetase (NRPS) proteins to produce
      peptide antibiotics and siderophores. The catalytic domains of the NRPS proteins
      are usually linked in large multidomain proteins. Often, additional proteins are
      coexpressed with NRPS proteins that modify the NRPS peptide products, ensure the
      availability of substrate building blocks, or play a role in the import or export
      of the NRPS product. Many NRPS clusters include a small protein of approximately
      80 amino acids with homology to the MbtH protein of mycobactin synthesis in
      Mycobacteria tuberculosis; no function has been assigned to these proteins.
      Pseudomonas aeruginosa utilizes an NRPS cluster to synthesize the siderophore
      pyoverdine. The pyoverdine peptide contains a dihydroxyquinoline-based
      chromophore, as well as two formyl-N-hydroxyornithine residues, which are
      involved in iron binding. The pyoverdine cluster contains four modular NRPS
      enzymes and 10-15 additional proteins that are essential for pyoverdine
      production. Coexpressed with the pyoverdine synthetic enzymes is a 72-amino acid
      MbtH-like family member designated PA2412. We have determined the three
      dimensional structure of the PA2412 protein and describe here the structure and
      the location of conserved regions. Additionally, we have further analyzed a
      deletion mutant of the PA2412 protein for growth and pyoverdine production. Our
      results demonstrate that PA2412 is necessary for the production or secretion of
      pyoverdine at normal levels. The PA2412 deletion strain is able to use
      exogenously produced pyoverdine, showing that there is no defect in the uptake or
      utilization of the iron-pyoverdine complex.

PMID- 17502379
TI  - Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin
      (mTOR) via an mTOR signaling motif.
AB  - Tumors that form as a result of heightened mammalian target of rapamycin (mTOR)
      signaling are highly vascularized. This process of angiogenesis is regulated
      through hypoxia-inducible factor (HIF)-mediated transcription of angiogenic
      factors. It is recognized that inhibition of mTOR with rapamycin can diminish the
      process of angiogenesis. Our work shows that activation of mTOR by Ras homologue
      enriched in brain (Rheb) overexpression potently enhances the activity of
      HIF1alpha and vascular endothelial growth factor (VEGF)-A secretion during
      hypoxia, which is reversed with rapamycin. Mutants of Rheb, which do not bind
      guanine nucleotide (D60K, D60V, N119I, and D122N) and are unable to activate
      mTOR, inhibit the activity of HIF when overexpressed. We show that regulatory
      associated protein of mTOR (Raptor) interacts with HIF1alpha and requires an mTOR
      signaling (TOS) motif located in the N terminus of HIF1alpha. Furthermore, a
      mutant of HIF1alpha lacking this TOS motif dominantly impaired HIF activity
      during hypoxia and was unable to bind to the co-activator CBP/p300. Rapamycin
      treatments do not affect the stability of HIF1alpha and modulate HIF activity via
      a Von Hippel-Lindau (VHL)-independent mechanism. We demonstrate that the high
      levels of HIF activity in cells devoid of TSC2 can be reversed by treatments with
      rapamycin or the readdition of TSC2. Our work explains why human cancers with
      aberrant mTOR signaling are prone to angiogenesis and suggests that inhibition of
      mTOR with rapamycin might be a suitable therapeutic strategy.

PMID- 17502380
TI  - Nedd4-2 catalyzes ubiquitination and degradation of cell surface ENaC.
AB  - Epithelial Na(+) absorption is regulated by Nedd4-2, an E3 ubiquitin-protein
      ligase that reduces expression of the epithelial Na(+) channel ENaC at the cell
      surface. Defects in this regulation cause Liddle syndrome, an inherited form of
      hypertension. Previous work found that Nedd4-2 binds to ENaC via PY motifs
      located in the C termini of alpha-, beta-, and gammaENaC. However, little is
      known about the mechanism by which Nedd4-2 regulates ENaC surface expression.
      Here we found that Nedd4-2 catalyzes ubiquitination of alpha-, beta-, and
      gammaENaC; Nedd4-2 overexpression increased ubiquitination, whereas Nedd4-2
      silencing decreased ubiquitination. Although Nedd4-2 increased both
      mono/oligoubiquitinated and multiubiquitinated forms of ENaC, monoubiquitination
      was sufficient for Nedd4-2 to reduce ENaC surface expression and reduce ENaC
      current. Ubiquitination was disrupted by Liddle syndrome-associated mutations in
      ENaC or mutation of the catalytic HECT domain in Nedd4-2. Several findings
      suggest that the interaction between Nedd4-2 and ENaC is localized to the cell
      surface. First, Nedd4-2 bound to a population of ENaC at the cell surface.
      Second, Nedd4-2 catalyzed ubiquitination of cell surface ENaC. Third, Nedd4-2
      selectively reduced ENaC expression at the cell surface but did not alter the
      quantity of immature ENaC in the biosynthetic pathway. Finally, Nedd4-2 induced
      degradation of the cell surface pool of ENaC. Together, the data suggest a model
      in which Nedd4-2 binds to and ubiquitinates ENaC at the cell surface, which
      targets surface ENaC for degradation, and thus, reduces epithelial Na(+)
      transport.

PMID- 17502381
TI  - Abnormal collagen fibrils in cartilage of matrilin-1/matrilin-3-deficient mice.
AB  - Matrilins are oligomeric extracellular matrix adaptor proteins mediating
      interactions between collagen fibrils and other matrix constituents. All four
      matrilins are expressed in cartilage and mutations in the human gene encoding
      matrilin-3 (MATN3) are associated with different forms of chondrodysplasia.
      Surprisingly, however, Matn3-null as well as Matn1- and Matn2-null mice do not
      show an overt skeletal phenotype, suggesting a dominant negative pathomechanism
      for the human disorders and redundancy/compensation among the family members in
      the knock-out situation. Here, we show that mice lacking both matrilin-1 and
      matrilin-3 develop an apparently normal skeleton, but exhibit biochemical and
      ultrastructural abnormalities of the knee joint cartilage. At the protein level,
      an altered SDS-PAGE band pattern and a clear up-regulation of the homotrimeric
      form of matrilin-4 were evident in newborn Matn1/Matn3 and Matn1 knock-out mice,
      but not in Matn3-null mice. The ultrastructure of the cartilage matrix after
      conventional chemical fixation was grossly normal; however, electron microscopy
      of high pressure frozen and freeze-substituted samples, revealed two consistent
      observations: 1) moderately increased collagen fibril diameters throughout the
      epiphysis and the growth plate in both single and double mutants; and 2)
      increased collagen volume density in Matn1(-/-)/Matn3(-/-) and Matn3(-/-) mice.
      Taken together, our results demonstrate that matrilin-1 and matrilin-3 modulate
      collagen fibrillogenesis in cartilage and provide evidence that biochemical
      compensation might exist between matrilins.

PMID- 17502382
TI  - Structure of Escherichia coli Lytic transglycosylase MltA with bound
      chitohexaose: implications for peptidoglycan binding and cleavage.
AB  - Crystal structures of an inactive mutant (D308A) of the lytic transglycosylase
      MltA from Escherichia coli have been determined in two different apo-forms, as
      well as in complex with the substrate analogue chitohexaose. The chitohexaose
      binds with all six saccharide residues in the active site groove, with an intact
      glycosidic bond at the bond cleavage center. Its binding induces a large
      reorientation of the two structural domains in MltA, narrowing the active site
      groove and allowing tight interactions of the oligosaccharide with residues from
      both domains. The structures identify residues in MltA with key roles in the
      binding and recognition of peptidoglycan and confirm that Asp-308 is the single
      catalytic residue, acting as a general acid/base. Moreover, the structures
      suggest that catalysis involves a high energy conformation of the scissile
      glycosidic linkage and that the putative oxocarbenium ion intermediate is
      stabilized by the dipole moment of a nearby alpha-helix.

PMID- 17502383
TI  - Characterization of heme as activator of Toll-like receptor 4.
AB  - Heme is an ancient and ubiquitous molecule present in organisms of all kingdoms,
      composed of an atom of iron linked to four ligand groups of porphyrin. A high
      amount of free heme, a potential amplifier of the inflammatory response, is a
      characteristic feature of diseases with increased hemolysis or extensive cell
      damage. Here we demonstrate that heme, but not its analogs/precursors, induced
      tumor necrosis factor-alpha (TNF-alpha) secretion by macrophages dependently on
      MyD88, TLR4, and CD14. The activation of TLR4 by heme is exquisitely strict,
      requiring its coordinated iron and the vinyl groups of the porphyrin ring.
      Signaling of heme through TLR4 depended on an interaction distinct from the one
      established between TLR4 and lipopolysaccharide (LPS) since anti-TLR4/MD2
      antibody or a lipid A antagonist inhibited LPS-induced TNF-alpha secretion but
      not heme activity. Conversely, protoporphyrin IX antagonized heme without
      affecting LPS-induced activation. Moreover, heme induced TNF-alpha and
      keratinocyte chemokine but was ineffective to induce interleukin-6, interleukin
      12, and interferon-inducible protein-10 secretion or co-stimulatory molecule
      expression. These findings support the concept that the broad ligand specificity
      of TLR4 and the different activation profiles might in part reside in its ability
      to recognize different ligands in different binding sites. Finally, heme induced
      oxidative burst, neutrophil recruitment, and heme oxygenase-1 expression
      independently of TLR4. Thus, our results presented here reveal a previous
      unrecognized role of heme as an extracellular signaling molecule that affects the
      innate immune response through a receptor-mediated mechanism.

PMID- 17502384
TI  - Mucosal immunization with a novel nanoemulsion-based recombinant anthrax
      protective antigen vaccine protects against Bacillus anthracis spore challenge.
AB  - The currently available commercial human anthrax vaccine requires multiple
      injections for efficacy and has side effects due to its alum adjuvant. These
      factors limit its utility when immunizing exposed populations in emergent
      situations. We evaluated a novel mucosal adjuvant that consists of a nontoxic,
      water-in-oil nanoemulsion (NE). This material does not contain a proinflammatory
      component but penetrates mucosal surfaces to load antigens into dendritic cells.
      Mice and guinea pigs were intranasally immunized with recombinant Bacillus
      anthracis protective antigen (rPA) mixed in NE as an adjuvant. rPA-NE
      immunization was effective in inducing both serum anti-PA immunoglobulin G (IgG)
      and bronchial anti-PA IgA and IgG antibodies after either one or two mucosal
      administrations. Serum anti-PA IgG2a and IgG2b antibodies and PA-specific
      cytokine induction after immunization indicate a Th1-polarized immune response.
      rPA-NE immunization also produced high titers of lethal-toxin-neutralizing serum
      antibodies in both mice and guinea pigs. Guinea pigs nasally immunized with rPA
      NE vaccine were protected against an intradermal challenge with approximately
      1,000 times the 50% lethal dose ( approximately 1,000x LD(50)) of B. anthracis
      Ames strain spores (1.38 x 10(3) spores), which killed control animals within 96
      h. Nasal immunization also resulted in 70% and 40% survival rates against
      intranasal challenge with 10x LD(50) and 100x LD(50) (1.2 x 10(6) and 1.2 x
      10(7)) Ames strain spores. Our results indicate that NE can effectively adjuvant
      rPA for intranasal immunization. This potentially could lead to a needle-free
      anthrax vaccine requiring fewer doses and having fewer side effects than the
      currently available human vaccine.

PMID- 17502385
TI  - Mellowing out: adaptation to commensalism by Escherichia coli asymptomatic
      bacteriuria strain 83972.

PMID- 17502386
TI  - Role of primary human alveolar epithelial cells in host defense against
      Francisella tularensis infection.
AB  - Francisella tularensis, an intracellular pathogen, is highly virulent when
      inhaled. Alveolar epithelial type I (ATI) and type II (ATII) cells line the
      majority of the alveolar surface and respond to inhaled pathogenic bacteria via
      cytokine secretion. We hypothesized that these cells contribute to the lung
      innate immune response to F. tularensis. Results demonstrated that the live
      vaccine strain (LVS) contacted ATI and ATII cells by 2 h following intranasal
      inoculation of mice. In culture, primary human ATI or ATII cells, grown on
      transwell filters, were stimulated on the apical (AP) surface with virulent F.
      tularensis Schu 4 or LVS. Basolateral (BL) conditioned medium (CM), collected 6
      and 24 h later, was added to the BL surfaces of transwell cultures of primary
      human pulmonary microvasculature endothelial cells (HPMEC) prior to the addition
      of polymorphonuclear leukocytes (PMNs) or dendritic cells (DCs) to the AP
      surface. HPMEC responded to S4- or LVS-stimulated ATII, but not ATI, CM as
      evidenced by PMN and DC migration. Analysis of the AP and BL ATII CM revealed
      that both F. tularensis strains induced various levels of a variety of cytokines
      via NF-kappaB activation. ATII cells pretreated with an NF-kappaB inhibitor prior
      to F. tularensis stimulation substantially decreased interleukin-8 secretion,
      which did not occur through Toll-like receptor 2, 2/6, 4, or 5 stimulation. These
      data indicate a crucial role for ATII cells in the innate immune response to F.
      tularensis.

PMID- 17502387
TI  - Enucleated L929 cells support invasion, differentiation, and multiplication of
      Trypanosoma cruzi parasites.
AB  - Cell infection with Trypanosoma cruzi, the agent of Chagas' disease, begins with
      the uptake of infective trypomastigotes within phagosomes and their release into
      the cytosol, where they transform into replicating amastigotes; the latter, in
      turn, differentiate into cytolytically released and infective trypomastigotes. We
      ask here if the T. cruzi infection program can develop in enucleated host cells.
      Monolayers of L929 cells, enucleated by centrifugation in the presence of
      cytochalasin B and kept at 34 degrees C to extend the survival of cytoplasts,
      were infected with parasites of the CL strain. Percent infection, morphology,
      stage-specific markers, and numbers of parasites per cell were evaluated in
      nucleated and enucleated cells, both of which were present in the same
      preparations. Parasite uptake, differentiation and multiplication of amastigotes,
      development of epimastigote- and trypomastigote-like forms, and initial cytolytic
      release of parasites were all documented for cytoplasts and nucleated cells.
      Although the doubling times were similar, parasite loads at 48 and 72 h were
      significantly lower in the cytoplasts than in nucleated cells. Similar results
      were obtained with the highly virulent strain Y as well as with strains CL-14 and
      G, which exhibit low virulence for mice. Cytoplasts could also be infected with
      the CL strain 24 or 48 h after enucleation. Thus, infection of cells by T. cruzi
      can take place in enucleated host cells, i.e., in the absence of modulation of
      chromosomal and nucleolar gene transcription and of RNA modification and
      processing in the nucleus.

PMID- 17502388
TI  - Influence of Mycobacterium avium subsp. paratuberculosis on colitis development
      and specific immune responses during disease.
AB  - The granulomatous and intramural inflammation observed in cases of inflammatory
      bowel diseases (IBD) and veterinary Johne's disease suggests that Mycobacterium
      avium subsp. paratuberculosis is a causative agent. However, an incomplete
      understanding of the immunological steps responsible for the pathologies of IBD
      makes this conclusion uncertain. Sera from interleukin-10-deficient (IL-10(-/-))
      mice with spontaneous colitis displayed significantly higher M. avium subsp.
      paratuberculosis-specific immunoglobulin G2a antibody responses than did sera
      from similar mice without disease. Pathogen-free IL-10(-/-) mice received control
      vehicle or the vehicle containing heat-killed or live M. avium subsp.
      paratuberculosis. Mucosal CD4(+) T cells from the mice that developed colitis
      proliferated and secreted higher levels of gamma interferon and tumor necrosis
      factor alpha after ex vivo stimulation with a Vbeta11(+) T-cell receptor
      restricted peptide from the MPT59 antigen (Ag85B) than those secreted from cells
      from mice before the onset of colitis. The data from this study provide important
      information regarding the mechanisms of colitis in IL-10(-/-) mice, which are
      driven in part by Ag85B-specific T cells. The data suggest a plausible mechanism
      of Ag-specific T-cell responses in colitis driven by potent Ags conserved in
      Mycobacterium species.

PMID- 17502389
TI  - Mechanisms of Chlamydia trachomatis entry into nonphagocytic cells.
AB  - The mechanisms of entry for the obligate intracellular bacterium C. trachomatis
      were examined by functional disruption of proteins essential for various modes of
      entry. RNA interference was used to disrupt proteins with established roles in
      clathrin-mediated endocytosis (clathrin heavy chain, dynamin-2, heat shock 70-kDa
      protein 8, Arp2, cortactin, and calmodulin), caveola-mediated endocytosis
      (caveolin-1, dynamin-2, Arp2, NSF, and annexin II), phagocytosis (RhoA, dynamin
      2, Rac1, and Arp2), and macropinocytosis (Pak1, Rac1, and Arp2). Comparative
      quantitative PCR analysis was performed on small interfering RNA-transfected HeLa
      cells to accurately determine the extent of C. trachomatis entry after these
      treatments. Key structural and regulatory factors associated with clathrin
      mediated endocytosis were found to be involved in Chlamydia entry, whereas those
      for caveola-mediated endocytosis, phagocytosis, and macropinocytosis were not.
      Thus, clathrin and its coordinate accessory factors were required for entry of C.
      trachomatis, although additional, uncharacterized mechanisms are also utilized.

PMID- 17502390
TI  - Protective role of Bacillus anthracis exosporium in macrophage-mediated killing
      by nitric oxide.
AB  - The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis
      to survive in activated macrophages is key to its germination and survival. In a
      previous publication, we discovered that exposure of primary murine macrophages
      to B. anthracis endospores upregulated NOS 2 concomitant with an .NO-dependent
      bactericidal response. Since NOS 2 also generates O(2).(-), experiments were
      designed to determine whether NOS 2 formed peroxynitrite (ONOO(-)) from the
      reaction of .NO with O(2).(-) and if so, was ONOO(-) microbicidal toward B.
      anthracis. Our findings suggest that ONOO(-) was formed upon macrophage infection
      by B. anthracis endospores; however, ONOO(-) does not appear to exhibit
      microbicidal activity toward this bacterium. In contrast, the exosporium of B.
      anthracis, which exhibits arginase activity, protected B. anthracis from
      macrophage-mediated killing by decreasing .NO levels in the macrophage. Thus, the
      ability of B. anthracis to subvert .NO production has important implications in
      the control of B. anthracis-induced infection.

PMID- 17502391
TI  - The Pseudomonas aeruginosa secreted protein PA2934 decreases apical membrane
      expression of the cystic fibrosis transmembrane conductance regulator.
AB  - We previously reported that Pseudomonas aeruginosa PA14 secretes a protein that
      can reduce the apical membrane expression of the cystic fibrosis transmembrane
      conductance regulator (CFTR) protein. Here we report that we have used a
      proteomic approach to identify this secreted protein as PA2934 [corrected], and
      we have named the gene cif, for CFTR inhibitory factor. We demonstrate that Cif
      is a secreted protein and is found associated with outer membrane-derived
      vesicles. Expression of Cif in Escherichia coli and purification of the C
      terminal six-His-tagged Cif protein showed that Cif is necessary and sufficient
      to mediate the reduction in apical membrane expression of CFTR and a concomitant
      reduction in CFTR-mediated Cl(-) ion secretion. Cif demonstrates epoxide
      hydrolase activity in vitro and requires a highly conserved histidine residue
      identified in alpha/beta hydrolase family enzymes to catalyze this reaction.
      Mutating this histidine residue also abolishes the ability of Cif to reduce
      apical membrane CFTR expression. Finally, we demonstrate that the cif gene is
      expressed in the cystic fibrosis (CF) lung and that nonmucoid isolates of P.
      aeruginosa show greater expression of the gene than do mucoid isolates. We
      propose a model in which the Cif-mediated decrease in apical membrane expression
      of CFTR by environmental isolates of P. aeruginosa facilitates the colonization
      of the CF lung by this microbe.

PMID- 17502392
TI  - Purine salvage pathways among Borrelia species.
AB  - Genome sequencing projects on two relapsing fever spirochetes, Borrelia hermsii
      and Borrelia turicatae, revealed differences in genes involved in purine
      metabolism and salvage compared to those in the Lyme disease spirochete Borrelia
      burgdorferi. The relapsing fever spirochetes contained six open reading frames
      that are absent from the B. burgdorferi genome. These genes included those for
      hypoxanthine-guanine phosphoribosyltransferase (hpt), adenylosuccinate synthase
      (purA), adenylosuccinate lyase (purB), auxiliary protein (nrdI), the
      ribonucleotide-diphosphate reductase alpha subunit (nrdE), and the ribonucleotide
      diphosphate reductase beta subunit (nrdF). Southern blot assays with multiple
      Borrelia species and isolates confirmed the presence of these genes in the
      relapsing fever group of spirochetes but not in B. burgdorferi and related
      species. TaqMan real-time reverse transcription-PCR demonstrated that the
      chromosomal genes (hpt, purA, and purB) were transcribed in vitro and in mice.
      Phosphoribosyltransferase assays revealed that, in general, B. hermsii exhibited
      significantly higher activity than did the B. burgdorferi cell lysate, and
      enzymatic activity was observed with adenine, hypoxanthine, and guanine as
      substrates. B. burgdorferi showed low but detectable phosphoribosyltransferase
      activity with hypoxanthine even though the genome lacks a discernible ortholog to
      the hpt gene in the relapsing fever spirochetes. B. hermsii incorporated
      radiolabeled hypoxanthine into RNA and DNA to a much greater extent than did B.
      burgdorferi. This complete pathway for purine salvage in the relapsing fever
      spirochetes may contribute, in part, to these spirochetes achieving high cell
      densities in blood.

PMID- 17502393
TI  - Survival of Chlamydia muridarum within dendritic cells.
AB  - Immune responses to Chlamydia trachomatis underlay both immunity and
      immunopathology. Immunopathology in turn has been attributed to chronic
      persistent infection with persistence being defined as the presence of organisms
      in the absence of replication. We hypothesized that dendritic cells (DCs) play a
      central role in Chlamydia immunity and immunopathology by favoring the long-term
      survival of C. muridarum. This hypothesis was examined based on (i) direct
      staining of Chlamydia in infected DCs to evaluate the development of inclusions,
      (ii) titration of infected DCs on HeLa cells to determine cultivability, and
      (iii) transfer of Chlamydia-infected DCs to naive mice to evaluate infectivity.
      The results show that Chlamydia survived within DCs and developed both typical
      and atypical inclusions that persisted in a subpopulation of DCs for more than 9
      days after infection. Since the cultivability of Chlamydia from DCs onto HeLa was
      lower than that estimated by the number of inclusions in DCs, this suggests that
      the organisms may be in state of persistence. Intranasal transfer of long-term
      infected DCs or DCs purified from the lungs of infected mice caused mouse lung
      infection, suggesting that in addition to persistent forms, infective Chlamydia
      organisms also developed within chronically infected DCs. Interestingly, after in
      vitro infection with Chlamydia, most DCs died. However, Chlamydia appeared to
      survive in a subpopulation of DCs that resisted infection-induced cell death.
      Surviving DCs efficiently presented Chlamydia antigens to Chlamydia-specific CD4+
      T cells, suggesting that the bacteria are able to both direct their own survival
      and still allow DC antigen-presenting function. Together, these results raise the
      possibility that Chlamydia-infected DCs may be central to the maintenance of T
      cell memory that underlies both immunity and immunopathology.

PMID- 17502394
TI  - Unique gene expression profiles in infants vaccinated with different strains of
      Mycobacterium bovis bacille Calmette-Guerin.
AB  - Vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) has variable
      efficacy in preventing tuberculosis. We hypothesized that some of this variation
      might be due to differences among BCG strains. To test this, neonates in Orizaba,
      Mexico, were vaccinated with one of three different BCG strains (BCG-Brazil
      [BBCG], BCG-Denmark [DBCG], or BCG-Japan [JBCG]). One year after vaccination,
      peripheral blood mononuclear cells (PBMC) were obtained and recall immune
      responses to culture filtrate proteins (CFP) of Mycobacterium tuberculosis were
      evaluated using quantitative real-time PCR. CFP-activated PBMC from BBCG- and
      DBCG-immunized children expressed high levels of cytokines characteristic of an
      adaptive immune response (gamma interferon, interleukin-2beta [IL-12beta], and IL
      27), while those from children immunized with JBCG did not. In contrast,
      vaccination with JBCG resulted in significantly greater expression of cytokines
      characteristic of a proinflammatory immune response (IL-1alpha, IL-1beta, IL-6,
      and IL-24) in PBMC activated with CFP compared to PBMC from children vaccinated
      with BBCG or DBCG. Thus, different strains of BCG can activate different immune
      pathways, which may affect long-term vaccine efficacy.

PMID- 17502395
TI  - Active and passive immunizations with the streptococcal esterase Sse protect mice
      against subcutaneous infection with group A streptococci.
AB  - The human pathogen group A Streptococcus (GAS) produces many secreted proteins
      that play important roles in GAS pathogenesis, including hydrolases that degrade
      proteins and nucleic acids. This study targets another kind of hydrolase,
      carboxylic esterase, with the objectives of identifying GAS esterase and
      determining whether it is a protective antigen. The putative esterase gene
      SPy1718 was cloned, and the recombinant protein (Sse) was prepared. Sse was
      detected in GAS culture supernatant, and patients with streptococcal pharyngitis
      seroconverted to Sse, indicating that Sse was produced in vivo and in vitro. Sse
      hydrolyzes p-nitrophenyl butyrate, and the residue (178)Ser is critical for this
      esterase activity. There are two Sse variant complexes according to the available
      genome databases, consistent with the previous finding of two antigenic Sse
      variants. Complex I includes serotypes M1, M2, M3, M5, M6, M12, and M18, whereas
      M4, M28, and M49 belong to complex II. Sse variants share >98% identity in amino
      acid sequence within each complex but have about 37% variation between the two
      groups. Active immunization with M1 Sse significantly protects mice against
      lethal subcutaneous infection with virulent M1 and M3 strains and inhibits GAS
      invasion of mouse skin tissue. Passive immunization with anti-Sse antiserum also
      significantly protects mice against subcutaneous GAS infection, indicating that
      the protection is mediated by Sse-specific antibodies. The results suggest that
      Sse plays an important role in tissue invasion and is an antigen protective in
      subcutaneous infection against GAS strains of more than one serotype.

PMID- 17502396
TI  - Enhanced immunity to Plasmodium falciparum circumsporozoite protein (PfCSP) by
      using Salmonella enterica serovar Typhi expressing PfCSP and a PfCSP-encoding DNA
      vaccine in a heterologous prime-boost strategy.
AB  - Two Salmonella enterica serovar Typhi strains that express and export a truncated
      version of Plasmodium falciparum circumsporozoite surface protein (tCSP) fused to
      Salmonella serovar Typhi cytolysin A (ClyA) were constructed as a first step in
      the development of a preerythrocytic malaria vaccine. Synthetic codon-optimized
      genes (t-csp1 and t-csp2), containing immunodominant B- and T-cell epitopes
      present in native P. falciparum circumsporozoite surface protein (PfCSP), were
      fused in frame to the carboxyl terminus of the ClyA gene (clyA::t-csp) in
      genetically stabilized expression plasmids. Expression and export of ClyA-tCSP1
      and ClyA-tCSP2 by Salmonella serovar Typhi vaccine strain CVD 908-htrA were
      demonstrated by immunoblotting of whole-cell lysates and culture supernatants.
      The immunogenicity of these constructs was evaluated using a "heterologous prime
      boost" approach consisting of mucosal priming with Salmonella serovar Typhi
      expressing ClyA-tCSP1 and ClyA-tCSP2, followed by parenteral boosting with PfCSP
      DNA vaccines pVR2510 and pVR2571. Mice primed intranasally on days 0 and 28 with
      CVD 908-htrA(pSEC10tcsp2) and boosted intradermally on day 56 with PfCSP DNA
      vaccine pVR2571 induced high titers of serum NANP immunoglobulin G (IgG)
      (predominantly IgG2a); no serological responses to DNA vaccination were observed
      in the absence of Salmonella serovar Typhi-PfCSP priming. Mice primed with
      Salmonella serovar Typhi expressing tCSP2 and boosted with PfCSP DNA also
      developed high frequencies of gamma interferon-secreting cells, which surpassed
      those produced by PfCSP DNA in the absence of priming. A prime-boost regimen
      consisting of mucosal delivery of PfCSP exported from a Salmonella-based live
      vector vaccine followed by a parenteral PfCSP DNA boosting is a promising
      strategy for the development of a live-vector-based malaria vaccine.

PMID- 17502397
TI  - PorA variable antigenic regions VR1, VR2, and VR3 of Neisseria meningitidis
      serogroups B and C isolated in Brazil from 1999 to 2004.
AB  - The high genetic diversity found among the PorA regions VR1 and VR2 of 101
      Neisseria meningitidis isolates from patients with meningococcal disease and
      healthy carriers in Brazil contrasts with the stability found in the PorA VR3 of
      these isolates. The presence of VR3 epitope variant 35 or 36 on the surfaces of
      87% of the strains analyzed suggests that these antigens should be considered for
      inclusion in new formulations of vaccines against serogroup B meningococci in
      Brazil.

PMID- 17502398
TI  - Differential stability and trade-off effects of pathoadaptive mutations in the
      Escherichia coli FimH adhesin.
AB  - FimH is the tip adhesin of mannose-specific type 1 fimbriae of Escherichia coli,
      which are critical to the pathogenesis of urinary tract infections. Point FimH
      mutations increasing monomannose (1M)-specific uroepithelial adhesion are
      commonly found in uropathogenic strains of E. coli. Here, we demonstrate the
      emergence of a mixed population of clonally identical E. coli strains in the
      urine of a patient with acute cystitis, where half of the isolates carried a
      glycine-to-arginine substitution at position 66 of the mature FimH. The R66
      mutation induced an unusually strong 1M-binding phenotype and a 20-fold advantage
      in mouse bladder colonization. However, E. coli strains carrying FimH-R66, but
      not the parental FimH-G66, had disappeared from the patient's rectal and urine
      samples collected from 29 to 44 days later, demonstrating within-host instability
      of the R66 mutation. No FimH variants with R66 were identified in a large (>600
      strains) sequence database of fimH-positive E. coli strains. However, several
      strains carrying genes encoding FimH with either S66 or C66 mutations appeared to
      be relatively stable in the E. coli population. Relative to FimH-R66, the FimH
      S66 and FimH-C66 variants mediated only moderate increases in 1M binding but
      preserved the ability to enhance binding under flow-induced shear conditions. In
      contrast, FimH-R66 completely lost shear-enhanced binding properties, with
      bacterial adhesion being inhibited by shear forces and lacking a rolling mode of
      binding. These functional trade-offs may determine the natural populational
      instability of this mutation or other pathoadaptive FimH mutations that confer
      dramatic increases in 1M binding strength.

PMID- 17502399
TI  - Possible correlates of long-term protection against Helicobacter pylori following
      systemic or combinations of mucosal and systemic immunizations.
AB  - The ability to induce long-term immunity to Helicobacter pylori is necessary for
      an effective vaccine. This study was designed to establish the most efficient
      route(s) (systemic, mucosal, or a combination) of immunization for induction of
      long-term immunity and to define correlates of protection. Mice were immunized
      orally alone (oral group), intramuscularly (i.m.) alone (i.m. group), orally
      followed by i.m. (oral/i.m. group), or i.m. followed by orally (i.m./oral group).
      Long-term protective immunity to oral H. pylori challenge was observed 3 months
      after immunization through the i.m. or oral/i.m. route. Protection correlated
      with an increase in H. pylori-specific interleukin-12 and both immunoglobulin G1
      (IgG1) and IgG2a serum titers following challenge. Mice that were not protected
      (oral or i.m./oral) had increased levels of IgA in both sera and Peyer's patches.
      This study demonstrates the ability to induce long-term immunity against H.
      pylori, provides correlates of protection, and illustrates the crucial role of
      the immunization route(s).

PMID- 17502400
TI  - Lack of immune responses to Mycobacterium tuberculosis DosR regulon proteins
      following Mycobacterium bovis BCG vaccination.
AB  - Mycobacterium bovis BCG is widely used as a vaccine against tuberculosis (TB),
      despite its variable protective efficacy. Relatively little is known about the
      immune response profiles following BCG vaccination in relation to protection
      against TB. Here we tested whether BCG vaccination results in immune responses to
      DosR (Rv3133c) regulon-encoded proteins. These so-called TB latency antigens are
      targeted by the immune system during persistent Mycobacterium tuberculosis
      infection and have been associated with immunity against latent M. tuberculosis
      infection. In silico analysis of the DosR regulon in BCG and M. tuberculosis
      showed at least 97% amino acid sequence homology, with 41 out of 48 genes being
      identical. Transcriptional profiling of 14 different BCG strains, under hypoxia
      and nitric oxide exposure in vitro, revealed a functional DosR regulon similar to
      that observed in M. tuberculosis. Next, we assessed human immune responses to a
      series of immunodominant TB latency antigens and found that BCG vaccination fails
      to induce significant responses to latency antigens. Similar results were
      obtained with BCG-vaccinated BALB/c mice. In contrast, responses to latency
      antigens were observed in individuals with suspected exposure to TB (as indicated
      by positive gamma interferon responses to TB-specific antigens ESAT-6 and CFP-10)
      and in mice vaccinated with plasmid DNA encoding selected latency antigens. Since
      immune responses to TB latency antigens have been associated with control of
      latent M. tuberculosis infection, our findings support the development of
      vaccination strategies incorporating DosR regulon antigens to complement and
      improve the current BCG vaccine.

PMID- 17502401
TI  - Eca1, a sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, is involved in stress
      tolerance and virulence in Cryptococcus neoformans.
AB  - The basidiomycetous fungal pathogen Cryptococcus neoformans is adapted to survive
      challenges in the soil and environment and within the unique setting of the
      mammalian host. A C. neoformans mutant was isolated with enhanced virulence in a
      soil amoeba model that nevertheless exhibits dramatically reduced growth at
      mammalian body temperature (37 degrees C). This mutant phenotype results from an
      insertion in the ECA1 gene, which encodes a sarcoplasmic/endoplasmic reticulum
      (ER) Ca2+-ATPase (SERCA)-type calcium pump. Infection in murine macrophages,
      amoebae (Acanthamoeba castellanii), nematodes (Caenorhabditis elegans), and wax
      moth (Galleria mellonella) larvae revealed that the eca1 mutants are virulent or
      hypervirulent at permissive growth temperatures but attenuated at 37 degrees C.
      Deletion mutants lacking the entire ECA1 gene were also hypersensitive to the
      calcineurin inhibitors cyclosporin and FK506 and to ER and osmotic stresses. An
      eca1Delta cna1Delta mutant lacking both Eca1 and the calcineurin catalytic
      subunit was more sensitive to high temperature and ER stresses than the single
      mutants and exhibited reduced survival in C. elegans and attenuated virulence
      towards wax moth larvae at temperatures that permit normal growth in vitro. Eca1
      is likely involved in maintaining ER function, thus contributing to stress
      tolerance and virulence acting in parallel with Ca2+-calcineurin signaling.

PMID- 17502402
TI  - Pyrophosphorolytic excision of nonobligate chain terminators by hepatitis C virus
      NS5B polymerase.
AB  - Nonobligate chain terminators, such as 2'-C-methylated nucleotides, block RNA
      synthesis by the RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV).
      Previous studies with related viral polymerases have shown that classical chain
      terminators lacking the 3'-hydroxyl group can be excised in the presence of
      pyrophosphate (PP(i)), which is detrimental to the inhibitory activity of these
      compounds. Here we demonstrate that the HCV RdRp enzyme is capable of removing
      both obligate and clinically relevant nonobligate chain terminators. Pyrimidines
      are more efficiently excised than are purines. The presence of the next
      complementary templated nucleotide literally blocks the excision of obligate
      chain terminators through the formation of a dead-end complex (DEC). However, 2'
      C-methylated CMP is still cleaved efficiently under these conditions. These
      findings show that a 2'-methylated primer terminus impedes nucleotide binding.
      The S282T mutation, associated with resistance to 2'-C-methylated nucleotides,
      does not affect the excision patterns. Thus, the decreased susceptibility to 2'-C
      methylated nucleotides appears to be based solely on improved discrimination
      between the inhibitor and its natural counterpart. In conclusion, our data
      suggest that the phosphorolytic excision of nonobligate, pyrimidine-based chain
      terminators can diminish their potency. The templated nucleotide does not appear
      to provide protection from excision through DEC formation.

PMID- 17502403
TI  - Inhibition of type III secretion in Salmonella enterica serovar Typhimurium by
      small-molecule inhibitors.
AB  - Type III secretion systems (T3SS) are conserved in many pathogenic gram-negative
      bacteria. Small molecules that specifically target T3SS in Yersinia and Chlamydia
      spp. have recently been identified. Here we show that two such compounds inhibit
      Salmonella T3SS-1, preventing secretion of T3SS-1 effectors, invasion of cultured
      epithelial cells, and enteritis in vivo.

PMID- 17502404
TI  - Efficacy of a novel rifamycin derivative, ABI-0043, against Staphylococcus aureus
      in an experimental model of foreign-body infection.
AB  - We compared the efficacy of a novel rifamycin derivative, ABI-0043, with that of
      rifampin, alone and in combination with levofloxacin, against methicillin
      susceptible Staphylococcus aureus ATCC 29213 in a guinea pig tissue-cage
      infection model. The MIC, logarithmic-growth-phase minimal bactericidal
      concentration, and stationary-growth-phase minimal bactericidal concentration of
      ABI-0043 were 0.001, 0.008, and 0.25 microg/ml, respectively; the corresponding
      concentrations of rifampin were 0.016, 0.8, and 3.6 microg/ml, respectively.
      After a single intraperitoneal dose of 12.5 mg/kg of body weight, the peak
      concentration in cage fluid was 1.13 micarog/ml of ABI-0043 and 0.98 microg/ml of
      rifampin. Five days after completion of treatment, levofloxacin administered
      alone (5 mg/kg/12 h) resulted in bacterial counts in cage fluid that were similar
      to those for untreated controls (>8.0 log(10) CFU/ml), whereas rifampin and ABI
      0043 administered alone (12.5 mg/kg/12 h) decreased the mean titers of bacteria
      +/- standard deviations to 1.43 +/- 0.28 log(10) and 1.57 +/- 0.53 log(10)
      CFU/ml, respectively, in cage fluid. In combination with levofloxacin, both
      rifamycins cleared bacteria from the cage fluid. The cure rates of cage
      associated infections with rifampin and ABI-0043 administered alone were 46% and
      58%, respectively, and increased to 88% and 92% in combination with levofloxacin.
      Emergence of rifamycin resistance was observed in 42% of cages after ABI-0043
      therapy and in 38% of cages after rifampin therapy; no emergence of resistance
      occurred with combination treatment with levofloxacin. In conclusion, ABI-0043
      had cure rates comparable to that of rifampin. ABI-0043 in combination with a
      quinolone has the potential for treatment of implant-associated infections caused
      by susceptible strains of S. aureus, potentially without drug-drug interactions.

PMID- 17502405
TI  - Promoter and transcription analysis of penicillin-binding protein genes in
      Streptococcus gordonii.
AB  - An optimally cross-linked peptidoglycan requires both transglycosylation and
      transpeptidation, provided by class A and class B penicillin-binding proteins
      (PBPs). Streptococcus gordonii possesses three class A PBPs (PBPs 1A, 1B, and 2A)
      and two class B PBPs (PBPs 2B and 2X) that are important for penicillin
      resistance. High-level resistance (MIC, > or =2 microg/ml) requires mutations in
      class B PBPs. However, although unmutated, class A PBPs are critical to
      facilitate resistance development (M. Haenni and P. Moreillon, Antimicrob. Agents
      Chemother. 50:4053-4061, 2006). Thus, their overexpression might be important to
      sustain the drug. Here, we determined the promoter regions of the S. gordonii
      PBPs and compared them to those of other streptococci. The extended -10 box was
      highly conserved and complied with a sigma(A)-type promoter consensus sequence.
      In contrast, the -35 box was poorly conserved, leaving the possibility of
      differential PBP regulation. Gene expression in a penicillin-susceptible parent
      (MIC, 0.008 microg/ml) and a high-level-resistant mutant (MIC, 2 microg/ml) was
      monitored using luciferase fusions. In the absence of penicillin, all PBPs were
      constitutively expressed, but their expression was globally increased (1.5 to 2
      times) in the resistant mutant. In the presence of penicillin, class A PBPs were
      specifically overexpressed both in the parent (PBP 2A) and in the resistant
      mutant (PBPs 1A and 2A). By increasing transglycosylation, class A PBPs could
      promote peptidoglycan stability when transpeptidase is inhibited by penicillin.
      Since penicillin-related induction of class A PBPs occurred in both susceptible
      and resistant cells, such a mutation-independent facilitating mechanism could be
      operative at each step of resistance development.

PMID- 17502406
TI  - Interaction of the GraRS two-component system with the VraFG ABC transporter to
      support vancomycin-intermediate resistance in Staphylococcus aureus.
AB  - Current treatment for serious infections caused by methicillin-resistant
      Staphylococcus aureus relies heavily upon the glycopeptide antibiotic vancomycin.
      Unfortunately, this practice has led to an intermediate resistance phenotype that
      is particularly difficult to treat in invasive staphylococcal diseases, such as
      septicemia and its metastatic complications, including endocarditis. Although the
      vancomycin-intermediate resistance phenotype has been linked to abnormal cell
      wall structures and autolytic rates, the corresponding genetic changes have not
      been fully elucidated. Previously, whole-genome array studies listed numerous
      genes that are overexpressed in vancomycin-intermediate sensitive strains,
      including graRS (SACOL0716 to -0717), encoding a two-component regulatory system
      (TCRS), as well as the adjacent vraFG (SACOL0718 to -0720), encoding an ATP
      binding cassette (ABC) transporter; but the exact contribution of these genes to
      increased vancomycin resistance has not been defined. In this study, we showed
      that isogenic strains with mutations in genes encoding the GraRS TCRS and the
      VraFG ABC transporter are hypersensitive to vancomycin as well as polymyxin B.
      Moreover, GraRS regulates the expression of the adjacent VraFG pump, reminiscent
      of gram-positive bacteriocin-immunity regulons. Mutations of graRS and vraFG also
      led to increased autolytic rates and a more negative net surface charge, which
      may explain, in part, to their increased sensitivity to cationic antimicrobial
      peptides. Taken together, these data reveal an important genetic mediator to the
      vancomycin-intermediate S. aureus phenotype and may hold clues to the selective
      pressures on staphylococci upon exposure to selective cationic peptide
      antibiotics used in clinical practice.

PMID- 17502407
TI  - Prevalence, characteristics, and molecular epidemiology of macrolide and
      fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae at
      five tertiary-care hospitals in Korea.
AB  - The genes erm(B), mef(A), and both erm(B) and mef(A) were identified in 42.6,
      10.1, and 47.3%, respectively, of the erythromycin-resistant Streptococcus
      pneumoniae isolates. Of the strains, 3.8% were nonsusceptible to levofloxacin and
      had 1 to 6 amino acid changes in the quinolone resistance-determining region,
      including a new mutation, Asn94Ser, in the product of parC. Levofloxacin with
      reserpine was highly specific for efflux screening.

PMID- 17502408
TI  - gyrA and parC Mutations and associated quinolone resistance in Vibrio anguillarum
      serotype O2b strains isolated from farmed Atlantic cod (Gadus morhua) in Norway.
AB  - MIC testing of Vibrio anguillarum isolates recovered from diseased farmed
      Atlantic cod revealed oxolinic acid MICs of < or =0.001, 0.06, and 16 microg ml(
      1). Single gyrA Ser-Ile substitutions were identified at position 83 of the
      intermediate and resistant strains, while a parC Ser-Leu substitution at position
      85 was found only in the resistant strain.

PMID- 17502409
TI  - Dual targeting of DNA gyrase and topoisomerase IV: target interactions of
      heteroaryl isothiazolones in Staphylococcus aureus.
AB  - Heteroaryl isothiazolones (HITZs) are antibacterial agents that display excellent
      in vitro activity against Staphylococcus aureus. We recently identified a series
      of these compounds that show potent bactericidal activities against methicillin
      resistant Staphylococcus aureus (MRSA). We report here the results of in vitro
      resistance studies that reveal potential underlying mechanisms of action. HITZs
      selected gyrA mutations exclusively in first-step mutants of wild-type S. aureus,
      indicating that in contrast to the case with most quinolones, DNA gyrase is the
      primary target. The compounds displayed low mutation frequencies (10(-9) to 10(
      10)) at concentrations close to the MICs and maintained low MICs (< or =0.016
      microg/ml) against mutants with single mutations in either gyrA or grlA (parC).
      These data suggested that HITZs possess significant inhibitory activities against
      target enzymes, DNA gyrase and topoisomerase IV. This dual-target inhibition was
      supported by low 50% inhibitory concentrations against topoisomerase IV as
      measured in a decatenation activity assay and against DNA gyrase as measured in a
      supercoiling activity assay. Good antibacterial activities (< or =1 microg/ml)
      against staphylococcal gyrA grlA double mutants, as well as low frequencies (10(
      9) to 10(-10)) of selection of still higher-level mutants, also suggested that
      HITZs remained active against mutant enzymes. We further demonstrated that HITZs
      exhibit good inhibition of both S. aureus mutant enzymes and thus continue to
      possess a novel dual-targeting mode of action against these mutant strains. In
      stepwise acquisition of mutations, HITZs selected quinolone resistance
      determining region mutations gyrA(Ser84Leu), grlA(Ser80Phe), grlA(Ala116Val), and
      gyrA(Glu88Lys) sequentially, suggesting that the corresponding amino acids are
      key amino acids involved in the binding of HITZs to topoisomerases. The overall
      profile of these compounds suggests the potential utility of HITZs in combating
      infections caused by S. aureus, including multidrug-resistant MRSA.

PMID- 17502410
TI  - Lack of an effect of antibiotic treatment on prolonged detection of chlamydial
      DNA in murine genital tract infection.
AB  - Mice treated with antibiotics early or late after active infection had resolved
      were examined for chlamydial DNA in endocervical swabs. The early eradication of
      infection limited oviduct pathology, despite the continued detection of
      chlamydial DNA by nested PCR. Late antibiotic treatment had no effect on the
      ability to detect DNA or oviduct pathology.

PMID- 17502411
TI  - Prospective randomized trial of empiric therapy with trimethoprim
      sulfamethoxazole or doxycycline for outpatient skin and soft tissue infections in
      an area of high prevalence of methicillin-resistant Staphylococcus aureus.
AB  - To evaluate empirical therapy with trimethoprim-sulfamethoxazole or doxycycline
      for outpatient skin and soft tissue infections in an area of high prevalence of
      methicillin-resistant Staphylococcus aureus, a randomized, prospective, open
      label investigation was performed. The overall clinical failure rate was 9%, with
      all failures occurring in the trimethoprim-sulfamethoxazole group. However, there
      was no significant difference between the clinical failure rate of empirical
      trimethoprim-sulfamethoxazole therapy and that of doxycycline therapy.

PMID- 17502412
TI  - Cytoplasmic-membrane anchoring of a class A beta-lactamase and its capacity in
      manifesting antibiotic resistance.
AB  - Bacterial beta-lactamases are the major causes of resistance to beta-lactam
      antibiotics. Three classes of these enzymes are believed to have evolved from
      ancestral penicillin-binding proteins (PBPs), enzymes responsible for bacterial
      cell wall biosynthesis. Both beta-lactamases and PBPs are able to efficiently
      form acyl-enzyme species with beta-lactam antibiotics. In contrast to beta
      lactamases, PBPs are unable to efficiently turn over antibiotics and therefore
      are susceptible to inhibition by beta-lactam compounds. Although both PBPs and
      gram-negative beta-lactamases operate in the periplasm, PBPs are anchored to the
      cytoplasmic membrane, but beta-lactamases are not. It is believed that beta
      lactamases shed the membrane anchor in the course of evolution. The significance
      of this event remains unclear. In an attempt to demonstrate any potential
      influence of the membrane anchor on the overall biological consequences of beta
      lactamases, we fused the TEM-1 beta-lactamase to the C-terminal membrane-anchor
      of penicillin-binding protein 5 (PBP5) of Escherichia coli. The enzyme was shown
      to express well in E. coli and was anchored to the cytoplasmic membrane.
      Expression of the anchored enzyme did not result in any changes in antibiotic
      resistance pattern of bacteria or growth rates. However, in the process of longer
      coincubation, the organism that harbored the plasmid for the anchored TEM-1 beta
      lactamase lost out to the organism transformed by the plasmid for the nonanchored
      enzyme over a period of 8 days of continuous growth. The effect would appear to
      be selection of a variant that eliminates the problematic protein through
      elimination of the plasmid that encodes it and not structural or catalytic
      effects at the protein level. It is conceivable that an evolutionary outcome
      could be the shedding of the sequence for the membrane anchor or alternatively
      evolution of these enzymes from nonanchored progenitors.

PMID- 17502413
TI  - Plasmid-mediated quinolone resistance determinant QnrB4 identified in France in
      an Enterobacter cloacae clinical isolate coexpressing a QnrS1 determinant.

PMID- 17502414
TI  - Atorvastatin is 10-fold more active in vitro than other statins against
      Plasmodium falciparum.

PMID- 17502415
TI  - Calcineurin inhibition or mutation enhances cell wall inhibitors against
      Aspergillus fumigatus.
AB  - Calcineurin mutation or inhibition enhanced the antifungal morphological effect
      of cell wall inhibitors caspofungin or nikkomycin Z against Aspergillus
      fumigatus. Quantification of 1,3-beta-d-glucan revealed decreased amounts in the
      calcineurin A (DeltacnaA) mutant. Calcineurin can be an excellent adjunct
      therapeutic target in combination with other cell wall inhibitors against A.
      fumigatus.

PMID- 17502417
TI  - Do people brace sensibly? Risk judgments and event likelihood.
AB  - Previous research has shown that people become pessimistic about potentially bad
      news to "brace for the worst." Three studies examined whether people brace
      differently for rare and common negative events. Results reveal that people brace
      more for rare negative events than for common negative events (Studies 1-3a), but
      only when the event is self-relevant (Study 3b). Results also show that people
      brace more for rare events when feedback is imminent (Study 1), when negative
      outcomes are salient (Study 2), and when the outcomes are important or
      consequential (Study 3a). The authors discuss several possible explanations for
      the findings, including ignorance of the base rate, random responding, and
      anchoring and adjustment, and ultimately suggest that people may brace "enough."

PMID- 17502416
TI  - Role for cell density in antifungal drug resistance in Candida albicans biofilms.
AB  - Biofilms of Candida albicans are less susceptible to many antifungal drugs than
      are planktonic yeast cells. We investigated the contribution of cell density to
      biofilm phenotypic resistance. Planktonic yeast cells in RPMI 1640 were
      susceptible to azole-class drugs, amphotericin B, and caspofungin at 1 x 10(3)
      cells/ml (standard conditions) using the XTT [2,3-bis(2-methoxy-4-nitro-5
      sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt] assay. As reported by
      others, as the cell concentration increased to 1 x 10(8) cells/ml, resistance was
      observed with 10- to 20-fold-greater MICs. Biofilms that formed in microtiter
      plate wells, like high-density planktonic organisms, were resistant to drugs.
      When biofilms were resuspended before testing, phenotypic resistance remained,
      but organisms, when diluted to 1 x 10(3) cells/ml, were susceptible. Drug
      containing medium recovered from high-cell-density tests inhibited low-cell
      density organisms. A fluconazole-resistant strain showed greater resistance at
      high planktonic cell density, in biofilm, and in resuspended biofilm than did low
      density planktonic or biofilm organisms. A strain lacking drug efflux pumps CDR1,
      CDR2, and MDR1, while susceptible at a low azole concentration, was resistant at
      high cell density and in biofilm. A strain lacking CHK1 that fails to respond to
      the quorum-sensing molecule farnesol had the same response as did the wild type.
      FK506, reported to abrogate tolerance to azole drugs at low cell density, had no
      effect on tolerance at high cell density and in biofilm. These observations
      suggested that cell density has a role in the phenotypic resistance of biofilm,
      that neither the drug efflux pumps tested nor quorum sensing through Chk1p
      contributes to resistance, and that azole drug tolerance at high cell density
      differs mechanistically from tolerance at low cell density.

PMID- 17502418
TI  - Automatic and self-reported attitudes in romantic relationships.
AB  - Two studies used response latency measures to assess automatic attitudes that
      individuals are unwilling or unable to reveal about their partners. In Study 1,
      participants (n = 51) in dating relationships completed two response latency
      measures (Time 1) and several relationship self-reports (Times 1 and 2).
      Participants who faced high barriers to exiting (BTE) their relationship
      generally showed a negative association between their relationship self-reports
      and automatic attitudes, and there was some evidence that automatic attitudes at
      Time 1 predicted relationship satisfaction at Time 2. Study 2 (n = 41 couples)
      replicated the BTE finding and showed that image-based response latency measures
      may assess automatic attitudes more effectively than word-based measures. A
      negative correlation between self-reported and automatic attitudes among high-BTE
      participants suggests that they may overreport relationship positivity to quell
      feelings of doubt about a relationship they cannot feasibly dissolve.

PMID- 17502419
TI  - Myelin protein zero/P0 phosphorylation and function require an adaptor protein
      linking it to RACK1 and PKC alpha.
AB  - Point mutations in the cytoplasmic domain of myelin protein zero (P0; the major
      myelin protein in the peripheral nervous system) that alter a protein kinase
      Calpha (PKCalpha) substrate motif (198HRSTK201) or alter serines 199 and/or 204
      eliminate P0-mediated adhesion. Mutation in the PKCalpha substrate motif (R198S)
      also causes a form of inherited peripheral neuropathy (Charcot Marie Tooth
      disease [CMT] 1B), indicating that PKCalpha-mediated phosphorylation of P0 is
      important for myelination. We have now identified a 65-kD adaptor protein that
      links P0 with the receptor for activated C kinase 1 (RACK1). The interaction of
      p65 with P0 maps to residues 179-197 within the cytoplasmic tail of P0. Mutations
      or deletions that abolish p65 binding reduce P0 phosphorylation and adhesion,
      which can be rescued by the substitution of serines 199 and 204 with glutamic
      acid. A mutation in the p65-binding sequence G184R occurs in two families with
      CMT, and mutation of this residue results in the loss of both p65 binding and
      adhesion function.

PMID- 17502420
TI  - Imaging analysis reveals mechanistic differences between first- and second-phase
      insulin exocytosis.
AB  - The mechanism of glucose-induced biphasic insulin release is unknown. We used
      total internal reflection fluorescence (TIRF) imaging analysis to reveal the
      process of first- and second-phase insulin exocytosis in pancreatic beta cells.
      This analysis showed that previously docked insulin granules fused at the site of
      syntaxin (Synt)1A clusters during the first phase; however, the newcomers fused
      during the second phase external to the Synt1A clusters. To reveal the function
      of Synt1A in phasic insulin exocytosis, we generated Synt1A-knockout (Synt1A(-/
      )) mice. Synt1A(-/-) beta cells showed fewer previously docked granules with no
      fusion during the first phase; second-phase fusion from newcomers was preserved.
      Rescue experiments restoring Synt1A expression demonstrated restoration of
      granule docking status and fusion events. Inhibition of other syntaxins, Synt3
      and Synt4, did not affect second-phase insulin exocytosis. We conclude that the
      first phase is Synt1A dependent but the second phase is not. This indicates that
      the two phases of insulin exocytosis differ spatially and mechanistically.

PMID- 17502421
TI  - Stra13 regulates satellite cell activation by antagonizing Notch signaling.
AB  - Satellite cells play a critical role in skeletal muscle regeneration in response
      to injury. Notch signaling is vital for satellite cell activation and myogenic
      precursor cell expansion but inhibits myogenic differentiation. Thus, precise
      spatial and temporal regulation of Notch activity is necessary for efficient
      muscle regeneration. We report that the basic helix-loop-helix transcription
      factor Stra13 modulates Notch signaling in regenerating muscle. Upon injury,
      Stra13(-/-) mice exhibit increased cellular proliferation, elevated Notch
      signaling, a striking regeneration defect characterized by degenerated myotubes,
      increased mononuclear cells, and fibrosis. Stra13(-/-) primary myoblasts also
      exhibit enhanced Notch activity, increased proliferation, and defective
      differentiation. Inhibition of Notch signaling ex vivo and in vivo ameliorates
      the phenotype of Stra13(-/-) mutants. We demonstrate in vitro that Stra13
      antagonizes Notch activity and reverses the Notch-imposed inhibition of
      myogenesis. Thus, Stra13 plays an important role in postnatal myogenesis by
      attenuating Notch signaling to reduce myoblast proliferation and promote myogenic
      differentiation.

PMID- 17502422
TI  - The budding yeast PP2ACdc55 protein phosphatase prevents the onset of anaphase in
      response to morphogenetic defects.
AB  - Faithful chromosome transmission requires establishment of sister chromatid
      cohesion during S phase, followed by its removal at anaphase onset. Sister
      chromatids are tethered together by cohesin, which is displaced from chromosomes
      through cleavage of its Mcd1 subunit by the separase protease. Separase is in
      turn inhibited, up to this moment, by securin. Budding yeast cells respond to
      morphogenetic defects by a transient arrest in G2 with high securin levels and
      unseparated chromatids. We show that neither securin elimination nor forced
      cohesin cleavage is sufficient for anaphase in these conditions, suggesting that
      other factors contribute to cohesion maintainance in G2. We find that the protein
      phosphatase PP2A bound to its regulatory subunit Cdc55 plays a key role in this
      process, uncovering a new function for PP2A(Cdc55) in controlling a noncanonical
      pathway of chromatid cohesion removal.

PMID- 17502424
TI  - The acetyltransferase activity of San stabilizes the mitotic cohesin at the
      centromeres in a shugoshin-independent manner.
AB  - Proper sister chromatid cohesion is critical for maintaining genetic stability.
      San is a putative acetyltransferase that is important for sister chromatid
      cohesion in Drosophila melanogaster, but not in budding yeast. We showed that San
      is critical for sister chromatid cohesion in HeLa cells, suggesting that this
      mechanism may be conserved in metazoans. Furthermore, although a small fraction
      of San interacts with the NatA complex, San appears to mediate cohesion
      independently. San exhibits acetyltransferase activity in vitro, and its activity
      is required for sister chromatid cohesion in vivo. In the absence of San, Sgo1
      localizes correctly throughout the cell cycle. However, cohesin is no longer
      detected at the mitotic centromeres. Furthermore, San localizes to the cytoplasm
      in interphase cells; thus, it may not gain access to chromosomes until mitosis.
      Moreover, in San-depleted cells, further depletion of Plk1 rescues the cohesion
      along the chromosome arms, but not at the centromeres. Collectively, San may be
      specifically required for the maintenance of the centromeric cohesion in mitosis.

PMID- 17502423
TI  - Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail
      can induce ERAD of MHC-I by viral E3 ligase mK3.
AB  - The mechanism by which substrates for endoplasmic reticulum-associated
      degradation are retrotranslocated to the cytosol remains largely unknown,
      although ubiquitination is known to play a key role. The mouse gamma-herpesvirus
      protein mK3 is a viral RING-CH-type E3 ligase that specifically targets nascent
      major histocompatibility complex I heavy chain (HC) for degradation, thus
      blocking the immune detection of virus-infected cells. To address the question of
      how HC is retrotranslocated and what role mK3 ligase plays in this action, we
      investigated ubiquitin conjugation sites on HC using mutagenesis and biochemistry
      approaches. In total, our data demonstrate that mK3-mediated ubiquitination can
      occur via serine, threonine, or lysine residues on the HC tail, each of which is
      sufficient to induce the rapid degradation of HC. Given that mK3 has numerous
      cellular and viral homologues, it will be of considerable interest to determine
      the pervasiveness of this novel mechanism of ubiquitination.

PMID- 17502425
TI  - Myosin-1a powers the sliding of apical membrane along microvillar actin bundles.
AB  - Microvilli are actin-rich membrane protrusions common to a variety of epithelial
      cell types. Within microvilli of the enterocyte brush border (BB), myosin-1a
      (Myo1a) forms an ordered ensemble of bridges that link the plasma membrane to the
      underlying polarized actin bundle. Despite decades of investigation, the function
      of this unique actomyosin array has remained unclear. Here, we show that addition
      of ATP to isolated BBs induces a plus end-directed translation of apical membrane
      along microvillar actin bundles. Upon reaching microvillar tips, membrane is
      "shed" into solution in the form of small vesicles. Because this movement
      demonstrates the polarity, velocity, and nucleotide dependence expected for a
      Myo1a-driven process, and BBs lacking Myo1a fail to undergo membrane translation,
      we conclude that Myo1a powers this novel form of motility. Thus, in addition to
      providing a means for amplifying apical surface area, we propose that microvilli
      function as actomyosin contractile arrays that power the release of BB membrane
      vesicles into the intestinal lumen.

PMID- 17502427
TI  - Knee-specific quality-of-life instruments: which ones measure symptoms and
      disabilities most important to patients?
AB  - BACKGROUND: Knee-specific quality-of-life instruments are commonly used outcome
      measures. However, they have not been compared for their ability to detect
      symptoms and disabilities important to patients. STUDY DESIGN: Cohort study
      (diagnosis); Level of evidence, 1. METHODS: Subjective portions of 11 knee
      specific instruments were consolidated. The frequency and importance of each item
      were assessed. One hundred fifty-three patients with anterior cruciate ligament
      ruptures, isolated meniscal tears, or osteoarthritis were polled. Instruments
      were ranked according to the number of items with high mean importance, high
      frequency importance product, and low mean importance, and according to the
      number endorsed by at least 51% of patients. RESULTS: For anterior cruciate
      ligament tears, the Mohtadi quality-of-life instrument scored highest in 3
      categories. For meniscal tears, the Western Ontario Meniscal Evaluation Tool
      scored highly in all 4 categories. For osteoarthritis, the Western Ontario and
      McMaster Universities Osteoarthritis Index scored highly in 4 categories. Of the
      general knee instruments, the International Knee Documentation Committee Standard
      Evaluation Form and the Knee Injury and Osteoarthritis Outcome Score scored
      favorably. CONCLUSION: The Mohtadi quality-of-life instrument, Western Ontario
      Meniscal Evaluation Tool, and Western Ontario and McMaster Universities
      Osteoarthritis Index-disease-specific instruments-contain many items important to
      patients. Of general knee instruments studied, the International Knee
      Documentation Committee Standard Evaluation Form and the Knee Injury and
      Osteoarthritis Outcome Score contain the most items important to patients.
      CLINICAL RELEVANCE: This study guides clinicians and researchers in selecting
      instruments that ensure that the patient's perspective is considered for outcome
      studies involving 3 common knee disorders.

PMID- 17502426
TI  - Zinc is a novel intracellular second messenger.
AB  - Zinc is an essential trace element required for enzymatic activity and for
      maintaining the conformation of many transcription factors; thus, zinc
      homeostasis is tightly regulated. Although zinc affects several signaling
      molecules and may act as a neurotransmitter, it remains unknown whether zinc acts
      as an intracellular second messenger capable of transducing extracellular stimuli
      into intracellular signaling events. In this study, we report that the cross
      linking of the high affinity immunoglobin E receptor (Fcepsilon receptor I
      [FcepsilonRI]) induced a release of free zinc from the perinuclear area,
      including the endoplasmic reticulum in mast cells, a phenomenon we call the zinc
      wave. The zinc wave was dependent on calcium influx and mitogen-activated protein
      kinase/extracellular signal-regulated kinase kinase activation. The results
      suggest that the zinc wave is involved in intracellular signaling events, at
      least in part by modulating the duration and strength of FcepsilonRI-mediated
      signaling. Collectively, our findings indicate that zinc is a novel intracellular
      second messenger.

PMID- 17502428
TI  - Pharmacological characterization of glycine-activated currents in HEK 293 cells
      expressing N-methyl-D-aspartate NR1 and NR3 subunits.
AB  - N-Methyl-D-aspartate (NMDA) receptors are important targets for drugs of abuse
      such as ethanol, toluene, and ketamine. Ligand-gated ion channels assembled from
      the NR1 and NR3 subunits have functional and pharmacological properties that are
      distinct from those of conventional NMDA receptors containing NR2 subunits. In
      the present study we used voltage-clamp electrophysiology to characterize
      excitatory glycine-activated receptors assembled from NR1, NR3A, and NR3B
      subunits expressed in human embryonic kidney (HEK) 293 cells. These glycine
      activated receptors were not stimulated by glutamate or kainic acid and were
      resistant to magnesium block. A wide variety of NMDA receptor antagonists
      including d-2-amino-5-phosphonovaleric acid, ifenprodil, memantine, (5R,10S)-(+)
      5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate
      (MK-801) or acamprosate did not inhibit glycine-activated NR1/NR3A/NR3B
      receptors. Likewise, these receptors were not affected by antagonists of
      inhibitory glycine receptors or glycine transporters. The NMDA receptor glycine
      site agonist, d-serine, partially activated NR1/NR3A/NR3B receptors, whereas the
      antagonist, 5,7-dichloro-kynurenic acid, inhibited receptor currents. Conversely,
      the antagonist, 7-chlorokynurenic acid, and the partial agonist, R-(+)-3-amino-1
      hydroxy-2-pyrrolidinone (HA-966), potentiated glycine-stimulated currents of
      these receptors. NR1/NR3A/NR3B receptor currents were inhibited by 10 to 21% by
      ethanol and toluene but were relatively insensitive to ketamine. Ethanol
      inhibition was enhanced in receptors expressing the NR1(L819A) mutant, whereas
      those containing NR1(F639A) or NR1(M813A) showed no change relative to the wild
      type NR1. The results of this study indicate that coexpression of NR1, NR3A, and
      NR3B subunits in HEK 293 cells results in glycineactivated receptors with novel
      functional and pharmacological properties.

PMID- 17502429
TI  - An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms
      under free-running and entrained conditions.
AB  - Casein kinase Iepsilon (CKIepsilon) is an essential component of the biological
      clock, phosphorylating PER proteins, and in doing so regulating their turnover
      and nuclear entry in oscillator cells of the suprachiasmatic nucleus (SCN).
      Although hereditary decreases in PER phosphorylation have been well
      characterized, little is known about the consequences of acute enzyme inhibition
      by pharmacological means. A novel reagent, 4-[3-cyclohexyl-5-(4-fluoro-phenyl)-3H
      imidazol-4-yl]-pyrimidin-2-ylamine (PF-670462), proved to be both a potent
      (IC(50) = 7.7 +/- 2.2 nM) and selective (>30-fold with respect to 42 additional
      kinases) inhibitor of CKIepsilon in isolated enzyme preparations; in transfected
      whole cell assays, it caused a concentration-related redistribution of nuclear
      versus cytosolic PER. When tested in free-running animals, 50 mg/kg s.c. PF
      670462 produced robust phase delays when dosed at circadian time (CT)9 (-1.97 +/-
      0.17 h). Entrained rats dosed in normal light-dark (LD) and then released to
      constant darkness also experienced phase delays that were dose- and time of
      dosing-dependent. PF-670462 yielded only phase delays across the circadian cycle
      with the most sensitive time at CT12 when PER levels are near their peak in the
      SCN. Most importantly, these drug-induced phase delays persisted in animals
      entrained and maintained in LD throughout the entire experiment; re-entrainment
      to the prevailing LD required days in contrast to the rapid elimination of the
      drug (t(1/2) = 0.46 +/- 0.04 h). Together, these results suggest that inhibition
      of CKIepsilon yields a perturbation of oscillator function that forestalls light
      as a zeitgeber, and they demonstrate that pharmacological tools such as PF-670462
      may yield valuable insight into clock function.

PMID- 17502430
TI  - Dehydrogenation of indoline by cytochrome P450 enzymes: a novel "aromatase"
      process.
AB  - Indoline derivatives possess therapeutic potential within a variety of drug
      candidates. In this study, we found that indoline is aromatized by cytochrome
      P450 (P450) enzymes to produce indole through a novel dehydrogenation pathway.
      The indole products can potentially be bioactivated to toxic intermediates
      through an additional dehydrogenation step. For example, 3-substituted indoles
      like 3-methylindole and zafirlukast [4-(5-cyclopentyloxy-carbonylamino-1-methyl
      indol-3-ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide] are dehydrogenated to
      form 3-methyleneindolenine electrophiles, which react with protein and/or DNA
      nucleophilic residues to cause toxicities. Another potentially significant
      therapeutic consequence of indoline aromatization is that the product indoles
      might have dramatically different therapeutic potency than the parent indolines.
      In this study, indoline was indeed efficiently aromatized by human liver
      microsomes and by several P450s, but not by flavin-containing monooxygenase (FMO)
      3. CYP3A4 had the highest aromatase activity. Four additional indoline
      metabolites [2,3,4,7-tetrahydro-4,5-epoxy-1H-indole (M1); N-hydroxyindole (M2), N
      hydroxyindoline (M3), and M4 ([1,4,2,5]dioxadiazino[2,3-a:5,6-a']diindole)] were
      characterized; none was a metabolite of indole. M1 was an arene oxide from P450
      oxidation, and M2, M3, and M4 were produced by FMO3. Our data indicated that
      indoline was oxidized to M3 and then to an intermediate indoline nitrone, which
      tautomerized to form M2, and subsequently dimerized to a di-indoline. This dimer
      was immediately oxidized by FMO3 or atmospheric oxygen to the final product, M4.
      No evidence was found for the P450-mediated production of an aliphatic alcohol
      from indoline that might dehydrate to produce indole. Therefore, P450 enzymes
      catalyze the novel "aromatase" metabolism of indoline to produce indole. The
      aromatase mechanism does not seem to occur through N-oxidation or dehydration of
      an alcohol but rather through a formal dehydrogenation pathway.

PMID- 17502431
TI  - Relative abuse liability of indiplon and triazolam in humans: a comparison of
      psychomotor, subjective, and cognitive effects.
AB  - Indiplon [N-methyl-N-[3-[3-(2-thienylcarbonyl)-pyrazolo[1,5-alpha]pyrimidin-7
      yl]phenyl]acetamide; NBI 34060] is a positive allosteric GABA(A) receptor
      modulator that is under development for the treatment of insomnia. This study
      compared the abuse potential of indiplon, a compound with preferential affinity
      for GABA(A) receptors containing an alpha(1) subunit, with triazolam in 21
      volunteers with histories of drug abuse. Placebo, triazolam (0.25, 0.5, and 0.75
      mg), and indiplon (30, 50, and 80 mg) were studied in counterbalanced order under
      double-blind conditions at two different residential research facilities. Both
      drugs impaired psychomotor and cognitive performance and produced similar dose
      related increases in participant and observer ratings of drug strength. The onset
      of action of both drugs was rapid (30 min); however, the duration of action of
      indiplon (3-4 h) was shorter than that of triazolam (4-6 h). The profiles of
      subjective effects of triazolam and indiplon were similar; however, a maximum of
      52% of participants identified indiplon as a benzodiazepine or barbiturate,
      compared with 81% of participants after 0.75 mg of triazolam. On participantrated
      subjective effects relevant to sedation, the slope of the triazolam dose-effect
      curve was significantly steeper than that of indiplon. Neither the largest doses
      of indiplon and triazolam nor the slope of the indiplon and triazolam dose-effect
      curves were significantly different from each other on any of the same-day or
      next-day measures of positive drug effects or next-day measures of reinforcing
      effects. Together, these data suggest that although the abuse potential of
      indiplon is not different from that of triazolam at these doses, psychomotor and
      cognitive impairment after large doses of indiplon might be less.

PMID- 17502432
TI  - A failure to communicate: let's get real about improving communication at the end
      of life.

PMID- 17502433
TI  - Strategies to improve recruitment of male volunteers in nonprofit agencies.
AB  - An increase in requests for volunteer services compounded by waning numbers of
      volunteers is a challenge to nonprofit organizations that are faced with the
      daunting task of recruiting and maintaining a large volunteer pool. This study
      explores alternate volunteer sources and suggests methods to be taken into
      account when recruiting male volunteers in various settings.

PMID- 17502434
TI  - "They should come out here ...": research findings on lack of local palliative
      care services for Australian aboriginal people.
AB  - Although Aboriginal Australians experience morbidity and mortality rates far
      greater than that of the wider Australian population, to date, their access to
      culturally appropriate palliative care services has remained unexplored. This
      article provides findings from an Australian National Health and Medical Research
      funded study that documents the availability of palliative care services to
      Aboriginal peoples of the Northern Territory, Australia. The data were collected
      through a series of open-ended, qualitative interviews with a cross section of
      Aboriginal peoples and health professionals conducted during a 2-year period. The
      findings provide an overview of the palliative care services that are presently
      available and reflect a serious lack of local, culturally appropriate palliative
      care services. This research shows the similarities in the struggles and
      difficulties faced by Australian Aboriginals and Indigenous peoples worldwide.
      The hope is that the suggestions put forward for improvement will one day be
      useful for the world's Indigenous peoples.

PMID- 17502435
TI  - Where do prevention and palliative care meet? A systematic literature study on
      the interfaces of two different health care sectors.
AB  - The objective of this study was to elaborate aspects of prevention in palliative
      care on the basis of available literature sources. We analyzed 223 articles from
      145 different journals covering the period from April 2001 to April 2006. Subject
      related categories were derived from the contents of these articles. Each article
      was subsequently allocated to one of the categories. In addition, we performed a
      free search in 6 selected text books on palliative care. The results revealed
      that the main textual emphasis had been placed on pain therapy and controlling
      the symptoms of bone metastasis. Altogether, the focus was on measures of
      tertiary prevention, whereas measures of primary prevention and preventive
      medicine received little attention. Therefore, the accentuation of the preventive
      aspect in the World Health Organization definition of palliative care is only
      rudimentarily reflected in the literature.

PMID- 17502436
TI  - A comprehensive community-based model for hospice care.
AB  - This study discusses the unique characteristics of a comprehensive community
      based model for hospice care. The data demonstrate that community-based hospice
      programs serve a population composed primarily of Medicare patients 75 years and
      older. It also addresses the primary clinical diagnoses for hospice patients,
      which include lung cancer, cognitive disability, cerebrovascular disease,
      congestive heart failure, chronic airway obstruction, colon cancer, renal
      failure, and prostate cancer. Finally, the study found that the primary caregiver
      for community-based hospice patients is the spouse, followed by other family
      members.

PMID- 17502437
TI  - On how increasing numbers of newer cancer therapies further delay referral to
      hospice: the increasing palliative care imperative.
AB  - Delay in referral of cancer patients to hospice until very near the end of life
      may deny patients and families optimal palliative care. A variety of factors may
      contribute to these delays. This article describes how the proliferation of newer
      anticancer therapies, although desirable overall, may further increase these
      delays. It is important for hospice personnel to understand these changes in
      medical oncology and to work to optimize palliative care delivery concomitantly
      with disease-remitting therapies.

PMID- 17502438
TI  - Using a pilot curriculum in geriatric palliative care to improve communication
      skills among medical students.
AB  - The purpose of this study was to assess the impact of an elective geriatric
      palliative care course on medical students' attitudes, knowledge, and behaviors
      regarding communication with terminally ill patients. Surveys were administered
      at the beginning and end of the elective. Despite a significant increase in
      knowledge about geriatric and palliative medicine (F=24.80; P<.001), there were
      no significant changes in students' self-reported behaviors when applying
      curriculum-based communication strategies. However, the qualitative analysis of
      open-ended questions showed that the curriculum intervention did result in an
      improvement in empowering message strategies for breaking bad news. The
      evaluation of the end-of-life curriculum needs to exceed the measurement of
      attitudes and knowledge and include behavioral assessment of end-of-life
      communication skills.

PMID- 17502439
TI  - The early identification of palliative care patients: preliminary processes and
      estimates from urban, family medicine practices.
AB  - Primary care providers are positioned to identify patients, well in advance of
      their deaths, who could benefit from palliative care services, but little is
      known about how to correctly identify these upstream palliative care patients.
      This article reports on efforts to devise a methodology for identifying such
      patients and to offer preliminary estimates of their prevalence in urban, primary
      care practices. The data presented here suggest 2 conclusions: (1) that
      electronic databases may be used to create a preliminary screen to assist
      clinicians in the early identification of patients in need of palliative care,
      and (2) that 1% to 3% of patients in primary care practices may benefit from
      palliative care services. Currently, there are no standards regarding the role of
      primary care providers in end-of-life care and it is hoped that this article will
      contribute to developing such standards.

PMID- 17502440
TI  - Disappearance of a stutter shortly before death.
AB  - A patient with a stutter caused by the trauma of the death of a loved one was
      able to recover normal speech 1 week before her death, which resulted from
      intestinal obstruction caused by ovarian cancer. The stutter appeared to have
      been overcome using a combination therapy of sophrology, self-regulation, and
      drug therapy. During a genuine resilience process, the patient was able to
      overcome an earlier existential fracture. In this final phase of life, health
      professionals and the family fully respected the patient's independence to remain
      in control of events. She repeatedly refused to have a nasogastric tube inserted
      to extract fecal matter from the stomach. This patient consequently repossessed
      her own language of expression in a body that was shattered by cancerous illness
      and the consequences of treatments. She thus managed to find a successful balance
      between the body, the spirit, and the brain.

PMID- 17502441
TI  - Recent advances in the palliative management of respiratory symptoms in advanced
      stage oncology patients.
AB  - Advanced-stage malignancies are often characterized by systemic complications
      related to primary tumor progression. Pulmonary complications such as cough and
      dyspnea are relatively common and can dramatically reduce quality of life and
      lead to inpatient or intensive care unit admission. Although cancer-induced cough
      can be improved with radiation therapy or chemotherapy, or both, it is often best
      managed with central-acting opioids. Dyspnea can arise from a range of etiologies
      that may or may not be related to the underlying malignant pulmonary disease.
      Recent advances in the management of malignant pleural effusion, central airway
      obstruction, and superior vena cava syndrome have allowed relatively noninvasive
      interventions to be performed that can significantly reduce dyspnea, minimize
      inpatient hospitalization, and improve the quality of life in patients where the
      major focus is palliative care.

PMID- 17502444
TI  - Surgical palliative care of advanced wounds.
AB  - The history of surgery is rich with accomplishments in wound care, a legacy that
      recently has been abandoned by many surgeons only to be taken up by nonsurgical
      providers. When dealing with advanced wounds at the end of life, such as pressure
      ulcers or venous stasis ulcers, goals of treatment are relief of pain,
      elimination of odor, and control of wound exudates and infection. Benefits and
      risks of surgical intervention must be discussed with the patient and family in
      terms of the patient's perceived prognosis, extent of tissue necrosis and
      infection, the rate of deterioration, and the underlying wound pathogenesis. When
      appropriate, the role of surgery looms large in the treatment of chronic,
      advanced wounds, especially when minimally invasive surgical techniques are used.

PMID- 17502445
TI  - Dueling interests: when surrogates collide.

PMID- 17502447
TI  - Racial differences in hospital discharge disposition among stroke patients in
      Maryland.
AB  - OBJECTIVE: The objective of this retrospective study was to assess the evidence
      for racial differences in discharge disposition among patients hospitalized for
      stroke. DATA: Hospital discharge data from the Maryland Health Services Cost
      Review Commission were used in the analysis. The data covered the period from
      January 2000 to September 2003. STUDY DESIGN: Discharge-disposition categories
      were ordered such that higher numbers corresponded to less desirable outcomes: 1
      = discharge to home; 2 = discharge to any medical care facility; 3 = death. We
      analyzed the influence of black race on the discharge disposition by estimating a
      partial proportional odds logit regression model that included demographic and
      clinical covariates. DATA EXTRACTION: The study inclusion criteria were 1) stroke
      (ICD9 431-434; 436-438) as a primary admission diagnosis and 2) patient race
      identified as black or white. Patients discharged against medical advice were
      excluded. The sample contained 51,564 stroke hospitalizations. PRINCIPAL
      FINDINGS: Based on the relative odds ratios (OR; 95% confidence interval [CI]),
      black males were more likely to be discharged to higher ranked (i.e., less
      desirable) discharge categories (OR = 1.66; CI 1.55-1.77) compared to white
      males. Black females were more likely to die (OR = 1.14; CI 1.02-1.28) and more
      likely either to die or to be discharged to medical care (OR = 1.38; CI 1.24
      1.54) compared to white males. CONCLUSIONS: Blacks are at greater mortality risk
      following stroke hospitalizations and face less desirable discharge dispositions
      if they survive. These results are consistent with prior reports of lower
      survival rates among blacks and are robust to adjustments for various confounding
      factors.

PMID- 17502448
TI  - A review and meta-analysis of prostate cancer utilities.
AB  - BACKGROUND: Health-related quality of life is a key issue in prostate cancer (PC)
      management. The authors summarized published utilities for common health-related
      quality of life outcomes of PC and determined how methodological factors affect
      them. METHODS: In their systematic review, the authors identified 23 articles in
      English, providing 173 unique utilities for PC health states, each obtained from
      2 to 422 respondents. Data were pooled using linear mixed-effects modeling with
      utilities clustered within the study, weighted by the number of respondents
      divided by the variance of each utility. RESULTS: In the base model, the
      estimated utility of the reference case (scenario of a metastatic PC patient with
      severe sexual symptoms, rated by non-PC patients using time tradeoff) was 0.76.
      Disease stage, symptom type and severity, source of utility, and scaling method
      were associated with utility differences of 0.10 to 0.32 (P < 0.05). Utilities
      from PC patients rating their own health were 0.14 higher than those from the
      reference case, but utilities from PC patients rating scenarios were lowest. Time
      tradeoff yielded the highest utilities. Computer administration yielded lower
      utilities than personal interview (P = 0.02). Neither the scale's high anchor nor
      study purpose had significant effects on utilities. CONCLUSIONS: This study
      provides pooled utility estimates for common PC health states and describes how
      clinical and methodological factors can significantly affect these values. When
      possible, utility estimates for a modeling application should be derived
      similarly. Formal data synthesis methods might be useful to researchers
      integrating utility data from heterogeneous sources. Further exploration of these
      methods for this purpose is warranted.

PMID- 17502449
TI  - The implications of using US-specific EQ-5D preference weights for cost
      effectiveness evaluation.
AB  - OBJECTIVE: The objective of this study is to examine the effect of country
      specific EQ-5D preference weights on the cost-effectiveness (CE) of initial
      pramipexole versus levodopa strategy in patients with Parkinson disease (PD).
      METHODS: A total of 301 subjects with PD were randomized to initial pramipexole
      or levodopa and followed every 3 months over a 4-year period. Subjects' health
      related quality of life (HRQOL) was measured using EQ-5D, and their health
      preferences were calculated using both the UK and US sets of weights. The
      effectiveness of pramipexole was defined as the additional quality-adjusted life
      years (QALY) gained compared to levodopa and was estimated as the area between
      the treatment-specific HRQOL profiles adjusted for baseline difference. RESULTS:
      Using the original UK weights, the incremental effectiveness was 0.155 QALYs,
      which resulted in the incremental CE ratio (ICER) of $42,989/QALY and a
      probability that pramipexole was cost-effective relative to levodopa of 0.57,
      0.77, and 0.82 when a QALY was valued at $50,000, $100,000, and $150,000,
      respectively. Using the US-specific weights resulted in lower incremental
      effectiveness (0.062 QALYs), higher ICER ($108,498/QALY), and a lower probability
      that pramipexole was cost-effective compared to levodopa at any valuation of QALY
      (0.23 for $50,000, 0.48 for $100,000, and 0.58 for $150,000). CONCLUSIONS:
      Country-specific preference weights in clinical-economic trials might have
      important effects on estimates of incremental cost-effectiveness. Using US
      preference weights rather than UK preference weights reduced the probability that
      pramipexole was cost-effective compared to levodopa.

PMID- 17502450
TI  - Review of medical reports on pedophilia.
AB  - The present report is a review of all 554 papers published on Medline on
      pedophilia. The first discussion is the history of the disorder from ancient
      Greece to the present time, especially the influence of the liberal country of
      the Netherlands, the North American Man-Boy Love Association, and the sexual
      crisis in the Catholic Church. One important question is the relationship between
      homosexual pedophilia and adult homosexuality. Evidence for and against this
      relationship is presented. Next discussed are the characteristics of the victim
      and the long lasting serious effects of sexual abuse. Laboratory correlations are
      included, especially phallometric tests in order to objectively measure the
      physical responses to sexual stimuli. Electrophysiological and radiographic tests
      are also mentioned, including electroencephalography, computed tomography,
      magnetic resonance imaging, and positron emission tomography scans. An important
      section is the characterization of pedophiles with emphasis on their frequent
      previous sexual abuse, their past, their present, and their anticipated future.
      The final topic is treatment of this disorder with surgery, medication,
      behavioral therapy and the combination of medication and behavioral therapy.

PMID- 17502451
TI  - Specialty differences in prescribing inhaled corticosteroids for children.
AB  - Prescription of daily inhaled corticosteroids for children with persistent asthma
      is infrequent compared with national practice guidelines. The authors conducted a
      national, cross-sectional survey of pediatricians and family physicians to
      identify specialty differences and factors associated with physician nonadherence
      to National Heart, Lung, and Blood Institute guidelines for prescribing inhaled
      corticosteroids. Adherence was defined as following the recommendation for >90%
      of cases. Response rate was 49% (343/694). Pediatrician and family physicians
      reported similar rates of adherence (54% vs 51%). Pediatricians and family
      physicians reported different barriers. Although both groups indicated that
      parent hesitancy and nonadherence were common barriers, the most common barrier
      for family physicians was a perceived cost of the asthma medications for
      families. Pediatricians were more likely to indicate that lack of time (21% vs
      10%) was a barrier to prescribing inhaled corticosteroids. In multivariate
      logistic analysis, the lack of a family/practice barrier (odds ratio, 0.27; 95%
      confidence interval, 0.13, 0.55) and physician agreement with the National Heart,
      Lung, and Blood Institute recommendation (odds ratio, 4.21; 95% confidence
      interval, 1.43, 12.3) was associated with self-reported adherence. Interventions
      to improve prescribing of inhaled corticosteroids should include strategies to
      address issues specific to pediatricians and family physicians.

PMID- 17502452
TI  - Music therapy in pediatrics.
AB  - The soothing effects of music have been well described over the centuries and
      across cultures. In more recent times, studies have shown the beneficial effects
      of music in alleviating symptoms in a wide variety of clinical and psychologic
      conditions. Music therapy has been primarily used as an intervention to control
      emotional states, in pain management, cognitive processing, and stress
      management. Stress is associated with increased production of the stress hormone
      cortisol, which is known to suppress immune responses. Several studies in the
      past few decades have demonstrated a positive effect of music therapy on reducing
      stress or increasing immune responses, or both. Music therapy should therefore be
      considered as a valuable addition to standard pharmacologic therapeutic
      modalities in enhancing the immune response and lowering stress levels in such
      conditions. This article reviews the role of music as a therapeutic modality and
      the future for music therapy, particularly in pediatrics.

PMID- 17502453
TI  - Small-molecule agonists of SHIP1 inhibit the phosphoinositide 3-kinase pathway in
      hematopoietic cells.
AB  - Because phosphoinositide 3-kinase (PI3K) plays a central role in cellular
      activation, proliferation, and survival, pharmacologic inhibitors targeting
      components of the PI3K pathway are actively being developed as therapeutics for
      the treatment of inflammatory disorders and cancer. These targeted drugs inhibit
      the activity of either PI3K itself or downstream protein kinases. However, a
      previously unexplored, alternate strategy is to activate the negative regulatory
      phosphatases in this pathway. The SH2-containing inositol-5'-phosphatase SHIP1 is
      a normal physiologic counter-regulator of PI3K in immune/hematopoietic cells that
      hydrolyzes the PI3K product phosphatidylinositiol-3,4,5-trisphosphate (PIP(3)).
      We now describe the identification and characterization of potent and specific
      small-molecule activators of SHIP1. These compounds represent the first small
      molecule activators of a phosphatase, and are able to activate recombinant SHIP1
      enzyme in vitro and stimulate SHIP1 activity in intact macrophage and mast cells.
      Mechanism of activation studies with these compounds suggest that they bind a
      previously undescribed, allosteric activation domain within SHIP1. Furthermore,
      in vivo administration of these compounds was protective in mouse models of
      endotoxemia and acute cutaneous anaphylaxis, suggesting that SHIP1 agonists could
      be used therapeutically to inhibit the PI3K pathway.

PMID- 17502454
TI  - The ABO blood group system and Plasmodium falciparum malaria.
AB  - In the century since the discovery of the ABO blood groups, numerous associations
      between ABO groups and disease have been noted. However, the selection pressures
      defining the ABO distributions remain uncertain. We review published information
      on Plasmodium falciparum infection and ABO blood groups. DNA sequence information
      dates the emergence and development of the group O allele to a period of
      evolution before human migration out of Africa, concomitant with P falciparum's
      activity. The current geographic distribution of group O is also consistent with
      a selection pressure by P falciparum in favor of group O individuals in malaria
      endemic regions. We critically review clinical reports of ABO and P falciparum
      infection, documenting a correlation between disease severity and ABO group.
      Finally, we review published data on the pathogenesis of P falciparum infection,
      and propose a biologic model to summarize the role of ABO blood groups in
      cytoadherence biology. Such ABO-related mechanisms also point to a new hypothesis
      to account for selection of the Le(a-b-) phenotype. Taken together, a broad range
      of available evidence suggests that the origin, distribution, and relative
      proportion of ABO blood groups in humans may have been directly influenced by
      selective genetic pressure from P falciparum infection.

PMID- 17502455
TI  - Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a
      novel marker essential for their anergy and suppressive function.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T cells (CD25(+) Treg cells) direct the
      maintenance of immunological self-tolerance by active suppression of
      autoaggressive T-cell populations. However, the molecules mediating the anergic
      state and regulatory function of CD25(+) Treg cells are still elusive. Using
      differential proteomics, we identified galectin-10, a member of the lectin
      family, as constitutively expressed in human CD25(+) Treg cells, while they are
      nearly absent in resting and activated CD4(+) T cells. These data were confirmed
      on the mRNA and protein levels. Single-cell staining and flow cytometry showed a
      strictly intracellular expression of galectin-10 in CD25(+) Treg cells. Specific
      inhibition of galectin-10 restored the proliferative capacity of CD25(+) Treg
      cells and abrogated their suppressive function. Notably, first identified here as
      expressed in human T lymphocytes, galectin-10 is essential for the functional
      properties of CD25(+) Treg cells.

PMID- 17502456
TI  - Cell adhesion induces p27Kip1-associated cell-cycle arrest through down
      regulation of the SCFSkp2 ubiquitin ligase pathway in mantle-cell and other non
      Hodgkin B-cell lymphomas.
AB  - Mounting evidence suggests that dynamic interactions between a tumor and its
      microenvironment play a critical role in tumor development, cell-cycle
      progression, and response to therapy. In this study, we used mantle cell lymphoma
      (MCL) as a model to characterize the mechanisms by which stroma regulate cell
      cycle progression. We demonstrated that adhesion of MCL and other non-Hodgkin
      lymphoma (NHL) cells to bone marrow stromal cells resulted in a reversible G(1)
      arrest associated with elevated p27(Kip1) and p21 (WAF1) proteins. The adhesion
      mediated p27(Kip1) and p21 increases were posttranslationally regulated via the
      down-regulation of Skp2, a subunit of SCF(Skp2) ubiquitin ligase. Overexpression
      of Skp2 in MCL decreased p27(Kip1), whereas inhibition of Skp2 by siRNA increased
      p27(Kip1) and p21 levels. Furthermore, we found cell adhesion up-regulated Cdh1
      (an activating subunit of anaphase-promoting complex [APC] ubiquitin ligase), and
      reduction of Cdh1 by siRNA induced Skp2 accumulation and hence p27(Kip1)
      degradation, thus implicating Cdh1 as an upstream effector of the Skp2/p27(Kip1)
      signaling pathway. Overall, this report, for the first time, demonstrates that
      cell-cell contact controls the tumor cell cycle via ubiquitin-proteasome
      proteolytic pathways in MCL and other NHLs. The understanding of this novel
      molecular pathway may prove valuable in designing new therapeutic approaches for
      modifying tumor cell growth and response to therapy.

PMID- 17502457
TI  - Respiratory virus infection among hematopoietic cell transplant recipients:
      evidence for asymptomatic parainfluenza virus infection.
AB  - The incidence of respiratory virus infection after hematopoietic cell
      transplantation (HCT) has probably been underestimated with conventional testing
      methods in symptomatic patients. This prospective study assessed viral infection
      episodes by testing weekly respiratory samples collected from HCT recipients,
      with and without symptoms reported by questionnaire, for 100 days after HCT.
      Samples were tested by culture and direct fluorescent antibody testing for
      respiratory syncytial virus (RSV), parainfluenza virus (PIV), and influenza A and
      B, and by quantitative reverse transcription-polymerase chain reaction for RSV,
      PIV, influenza A and B, and metapneumovirus (MPV). Of 122 patients, 30 (25%) had
      32 infection episodes caused by RSV (5), PIV (17), MPV (6), influenza (3), RSV,
      or influenza (1). PIV, with a cumulative incidence estimate of 17.9%, was the
      only virus for which asymptomatic infection was detected. Lower virus copy number
      in patients with no or one symptom compared with 2 or more symptoms was found for
      all viruses in all patients (P < .001), with PIV infection having a similar virus
      specific comparison (P = .004). Subclinical infection with PIV may help explain
      why infection-control programs that emphasize symptoms are effective against RSV
      and influenza but often not against PIV.

PMID- 17502458
TI  - Successful treatment of lymphoproliferative disease complicating primary
      immunodeficiency/immunodysregulatory disorders with reduced-intensity allogeneic
      stem-cell transplantation.
AB  - Lymphoproliferative disease (LPD) is a recognized complication of primary
      immunodeficiency (PID) and immunodysregulatory syndromes. Historically, it has a
      very poor outcome. For patients surviving LPD, myeloablative hematopoietic stem
      cell transplantation (SCT) was the only cure for the underlying PID, with a high
      risk of developing posttransplantation complications, including recurrent
      lymphoproliferative disease. We describe 8 patients with a range of PID and
      immunodysregulatory syndromes complicated by LPD. After initial treatment of the
      LPD (including the use of anti-CD20 monoclonal antibody, rituximab, in 6 of the
      patients), all patients underwent reduced-intensity conditioning (RIC) SCT with
      prospective monitoring for Epstein-Barr virus (EBV) viremia. After
      transplantation, 3 patients received rituximab, and 3 patients received
      prophylactic EBV-specific cytotoxic T-lymphocytes. Only 1 patient developed
      recurrent LPD posttransplantation, which responded to rituximab. All patients who
      underwent transplantation survive free of LPD and are cured of their PID at a
      median follow-up of 4 years (range, 1-7 years). With careful monitoring and pre
      emptive therapy, we advocate this RIC SCT approach to patients with PID who have
      pre-existing EBV-LPD.

PMID- 17502460
TI  - New insights about hematopoietic stem cell transplantation in
      adrenoleukodystrophy.

PMID- 17502459
TI  - Randomized, double-blind, placebo-controlled trial on symptomatic effects of
      coenzyme Q(10) in Parkinson disease.
AB  - BACKGROUND: Major hallmarks in the pathophysiology of Parkinson disease are
      cellular energy depletion and oxidative stress leading to cellular dysfunction
      and death. Coenzyme Q(10) (CoQ(10)) is an electron acceptor bridging
      mitochondrial complexes I and II/III and a potent antioxidant that consistently
      partially recovers the function of dopaminergic neurons. OBJECTIVE: To determine
      whether nanoparticular CoQ(10) is safe and displays symptomatic effects in
      patients with midstage Parkinson disease without motor fluctuations. DESIGN:
      Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel
      group, single-dose trial. SETTING: Academic and nonacademic movement disorder
      clinics. PATIENTS: One hundred thirty-one patients with Parkinson disease without
      motor fluctuations and a stable antiparkinsonian treatment. Intervention Random
      assignment to placebo or nanoparticular CoQ(10) (100 mg 3 times a day) for a
      treatment period of 3 months. Stratification criterion was levodopa treatment.
      MAIN OUTCOME MEASURE: The subjects underwent evaluation with the Unified
      Parkinson's Disease Rating Scale (UPDRS) at each visit on a monthly basis. The
      primary outcome variable was the change of the sum score of the UPDRS parts II
      and III between the baseline and 3-month visits. RESULTS: One hundred thirty-one
      subjects were randomized according to the protocol. The mean changes of the sum
      UPDRS parts II/III score were -3.69 for the placebo group and -3.33 for the
      CoQ(10) group (P = .82). Statistical analysis according to the stratification did
      not result in significant changes of the primary outcome variable. No secondary
      outcome measure showed a significant change between the placebo group and the
      CoQ(10) group. The frequency and quality of adverse events were similar in both
      treatment groups. CONCLUSIONS: Nanoparticular CoQ(10) at a dosage of 300 mg/d is
      safe and well tolerated and leads to plasma levels similar to 1200 mg/d of
      standard formulations. Add-on CoQ(10) does not display symptomatic effects in
      midstage Parkinson disease.

PMID- 17502461
TI  - Oculomotility disorders arising from disruptions in brainstem motor neuron
      development.
AB  - The identification and analysis of pedigrees with rare congenital oculomotility
      syndromes has led to the definition of the congenital cranial dysinnervation
      disorders. These disorders appear to result from mutations in genes that are
      essential to the normal development and/or connectivity of cranial motoneurons.
      This review highlights the clinical features and genetic etiology of 3 congenital
      cranial dysinnervation disorders: the human homeobox A1 (HOXA1) syndromes, in
      which early motoneuron development is disrupted; horizontal gaze palsy with
      progressive scoliosis, in which there is aberrant axonal targeting onto abducens
      motoneurons; and congenital fibrosis of the extraocular muscles type 1, in which
      there is aberrant axonal targeting onto the extraocular muscles.

PMID- 17502462
TI  - Contribution of intermediate progenitor cells to cortical histogenesis.
AB  - The mammalian cerebral cortex is the most cellularly complex structure in the
      animal kingdom. Almost all cortical neurons are produced during a limited
      embryonic period by cortical progenitor cells in a proliferative region that
      surrounds the ventricular system of the developing brain. The proliferative
      region comprises 2 distinct zones, the ventricular zone, which is a
      neuroepithelial layer directly adjacent to the ventricular lumen, and the
      subventricular zone, which is positioned superficial to the ventricular zone.
      Recent advances in molecular and cell biology have made possible the study of
      specific cell populations, and 2 cortical progenitor cell types, radial glial
      cells in the ventricular zone and intermediate progenitor cells in the
      subventricular zone, have been shown to generate neurons in the embryonic
      cerebral cortex. These findings have refined our understanding of cortical
      neurogenesis, with implications for understanding the causes of
      neurodevelopmental disorders and for their potential treatment.

PMID- 17502463
TI  - Genetic models of migraine.
AB  - Migraine is a common, disabling, complex brain disorder, presenting in attacks
      that may have up to 3 phases: a prodromal phase, the aura phase, and the headache
      phase. The pathogenesis of the aura and headache phases is reasonably well
      understood, but the mechanism by which migraine attacks are triggered is unknown.
      Most likely, migraineurs have a genetically determined reduced threshold for
      migraine triggers. Identifying "threshold genes" and deciphering their function
      will help to unravel the triggering mechanisms for migraine attacks. Familial
      hemiplegic migraine is a rare monogenic subtype of migraine with aura. Three
      genes have been identified for familial hemiplegic migraine. Recently, knock-in
      mice carrying human pathogenic FHM1 mutations were generated, which show
      behavioral, electrophysiological, and neurobiological characteristics in line
      with prevailing views of migraine physiological processes. Genetic migraine
      models will be useful in unraveling the triggering mechanisms for migraine
      attacks and in identifying novel migraine prophylactic targets and therapies.

PMID- 17502464
TI  - Magnetic resonance imaging detection of lesion progression in adult patients with
      X-linked adrenoleukodystrophy.
AB  - BACKGROUND: An inherited disorder, X-linked adrenoleukodystrophy (X-ALD) is known
      to cause progressive inflammatory demyelination. OBJECTIVE: To analyze the adult
      pattern of disease progression in X-ALD. DESIGN, SETTING, AND PATIENTS: We
      retrospectively assessed magnetic resonance (MR) images obtained in adult
      patients who had developed cerebral disease between January 1, 1985, and December
      31, 2005. We identified 103 adult patients with X-ALD with lesions on their MR
      images. Of these, 56 had serial MR examinations at least 1 year apart and were
      included in this study. Main Outcome Measure Progression of X-ALD lesions on MR
      images. RESULTS: On initial presentation, 17 patients with X-ALD had
      corticospinal tract lesions without splenium or genu involvement, 24 had
      symmetric corticospinal tract lesions with additional involvement of the splenium
      or genu, and 15 did not have corticospinal tract involvement but had other white
      matter lesions. In 18 of 21 patients with progressive lesions, corticospinal
      tract involvement preceded or occurred concurrently with progressive inflammatory
      demyelination. CONCLUSIONS: Brain MR imaging abnormalities in adults with X-ALD
      progress slower than those reported in childhood. The involvement of the
      corticospinal tracts is prominent and may at times represent a variant course of
      progressive inflammatory demyelination.

PMID- 17502465
TI  - Utility of urinalysis in discriminating cardioembolic stroke mechanism.
AB  - OBJECTIVE: To determine whether elevated urine erythrocyte (red blood cell) and
      leukocyte (white blood cell) counts, reflecting concomitant renal and cerebral
      emboli of cardiac origin, would be useful in discriminating cardioembolic (CE)
      from non-CE stroke in acute ischemic stroke. DESIGN: Consecutive patients
      presenting within 24 hours of ischemic stroke over 3(3/4) years were studied.
      Patient medical history and urinalysis data, including white blood cell count,
      red blood cell count, specific gravity, and glucose and protein levels at
      admission, were analyzed and compared with the final determination of stroke
      subtype. Multivariate analysis (CE vs non-CE stroke) was performed using a
      classification and regression tree that included all 5 urine variables as
      potential predictors. Additional predictors entered into the classification and
      regression tree model were age, presence of urinary tract infection at admission,
      history of hypertension, history of diabetes mellitus, and serum creatinine
      level. RESULTS: A total of 341 individuals met the study criteria. Their mean age
      was 68.6 years; 49.8% were female, 70.9% were white, and 38.7% had the CE stroke
      subtype. In bivariate analysis, age (P = .009), urine white blood cell count (P =
      .02), urine red blood cell count (P = .005), urine specific gravity (P = .02),
      and serum creatinine level (P = .02) were significantly higher in those with the
      CE vs the non-CE stroke subtype. In the classification and regression tree, 58.3%
      of those with CE stroke were correctly classified and 84.7% of those with non-CE
      stroke were correctly classified, for an overall accuracy of 71.5%. The best
      single predictor for the CE stroke subtype was a white blood cell count of
      greater than 14.5/microL, followed by a red blood cell count of greater than
      41.7/microL and a serum creatinine level greater than 1.08 mg/dL (>95.5
      micromol/L). Based on the distribution in the first 2 divisions in the tree, a
      patient could be placed into 1 of 4 categories that corresponded to 3 levels of
      CE stroke likelihood: low (25%), moderate (50%), and high (80%). CONCLUSION:
      Urinalysis may have utility in the early identification of the CE stroke subtype
      in patients with acute ischemic stroke.

PMID- 17502466
TI  - Transdermal rotigotine: double-blind, placebo-controlled trial in Parkinson
      disease.
AB  - OBJECTIVE: To assess the response to the rotigotine transdermal system (Neupro;
      Schwarz Pharma Ltd, Monheim, Germany), a nonergolinic dopamine agonist, in
      patients with early Parkinson disease. DESIGN: Randomized, double-blind,
      multicenter, placebo-controlled study. SETTING: Fifty sites in the United States
      and Canada. PATIENTS: Two hundred seventy-seven patients with early Parkinson
      disease. Eligibility was assessed by means of routine clinical and neurological
      examinations. Patients were randomized 2:1 to receive either rotigotine therapy
      or placebo. INTERVENTION: Treatment with the rotigotine transdermal system, 2, 4,
      or 6 mg during 24 hours, for 24 weeks. MAIN OUTCOME MEASURE: Percentage of
      subjects achieving a 20% response or greater (reduction) as assessed with the
      Unified Parkinson Disease Rating Scale subtotal (parts II [activities of daily
      living] and III [motor function]) from baseline to the end of the maintenance
      phase. RESULTS: Significant differences were observed between the rotigotine
      treated and placebo groups for the 20% responder rate (48% for the rotigotine
      group and 19% for the placebo group; P<.001), least squares mean change in
      Unified Parkinson Disease Rating Scale subtotal (parts II and III) score (-941
      for rotigotine vs -157 for placebo; P<.001), and percentage changes in Unified
      Parkinson Disease Rating Scale subtotal (parts II and III) score (-15.1% for
      rotigotine vs 7.3% for placebo; P<.001). Rotigotine treatment significantly
      increased the patients' Clinical Global Impression Scale scores (57% for
      rotigotine vs 30% for placebo; P<.001) and had a positive effect on their quality
      of life. The most common adverse events were application site reactions, nausea,
      and somnolence. Twenty-five (14%) of 181 patients in the rotigotine group
      withdrew from the study because of adverse effects. CONCLUSION: The rotigotine
      transdermal system consistently demonstrated statistically significant and
      clinically relevant efficacy over placebo in patients with early Parkinson
      disease and was well tolerated.

PMID- 17502467
TI  - Testosterone treatment in multiple sclerosis: a pilot study.
AB  - OBJECTIVE: To study the effect of testosterone supplementation on men with
      multiple sclerosis (MS). DESIGN, SETTING, AND PARTICIPANTS: Men are less
      susceptible to many autoimmune diseases, including MS. Possible causes for this
      include sex hormones and/or sex chromosome effects. Testosterone treatment
      ameliorates experimental allergic encephalomyelitis, an animal model of MS, but
      the effect of testosterone supplementation on men with MS is not known.
      Therefore, 10 men with relapsing-remitting MS were studied using a crossover
      design whereby each patient served as his own control. There was a 6-month
      pretreatment period followed by a 12-month period of daily treatment with 10 g of
      the gel containing 100 mg of testosterone. MAIN OUTCOME MEASURES: Clinical
      measures of disability and cognition (the Multiple Sclerosis Functional Composite
      and the 7/24 Spatial Recall Test) and monthly magnetic resonance imaging measures
      of enhancing lesion activity and whole brain volumes. RESULTS: One year of
      treatment with testosterone gel was associated with improvement in cognitive
      performance (P = .008) and a slowing of brain atrophy (P <.001). There was no
      significant effect of testosterone treatment on gadolinium-enhancing lesion
      numbers (P = .31) or volumes (P = .94). Lean body mass (muscle mass) was
      increased (P = .02). CONCLUSION: These exploratory findings suggest that
      testosterone treatment is safe and well tolerated and has potential
      neuroprotective effects in men with relapsing-remitting MS.

PMID- 17502468
TI  - Aggressive therapy for neurosarcoidosis: long-term follow-up of 48 treated
      patients.
AB  - BACKGROUND: Neurosarcoidosis (NS) is a relatively rare neurologic disorder for
      which no accepted treatment guidelines are available. Treatment with
      corticosteroids has been described as the primary means of controlling
      progressive symptoms. However, some physicians have recently advocated early
      intervention with alternative immunosuppressive therapies in patients who present
      with disabling symptoms. OBJECTIVE: To investigate our experience during the last
      decade regarding alternative immunosuppressive treatments, including
      corticosteroids and alternative therapies, in patients with NS. DESIGN:
      Observational, retrospective, consecutive case series with longitudinal follow
      up. SETTING: Allegheny Neurological Clinic. Patients Seventy-eight patients with
      sarcoidosis were evaluated and classified as having possible, probable, or
      definite NS according to accepted criteria. Five cases of isolated NS were also
      included. MAIN OUTCOME MEASURES: Patients with probable, definite, or isolated NS
      were scored before treatments and at final follow-up using estimated modified
      Rankin scores and the Disease Steps in Multiple Sclerosis scales. RESULTS: Forty
      three patients were categorized as having either definite or probable NS
      according to accepted criteria and an additional 5 as having isolated NS. Thirty
      patients were categorized as having possible NS and were not included in the
      analysis of treatment response. Patients had a mean +/- SD number of visits of
      7.2 +/- 6.4 and were followed up for a mean +/- SD of 44.1 +/- 43.6 months.
      Twenty patients were treated with pulse and/or maintenance corticosteroids alone.
      Twenty-six patients were treated with alternative immunosuppressive medications,
      with 23 of them receiving these medications at the time of diagnosis or within 6
      months of the diagnosis of NS. Of the patients treated with alternative
      immunosuppressive therapies, 18 (69%) improved, 4 (15%) remained stable, and 4
      (15%) worsened (including 1 death). Of the patients treated with corticosteroids
      alone, 7 (35%) improved, 11 (55%) remained stable, and 2 (10%) worsened. Two
      patients received no treatment. CONCLUSIONS: Approximately half of all patients
      with NS seen at our clinic were believed to have disabling disease and to be at
      high risk for disease progression. These high-risk patients were treated with
      corticosteroids plus alternative immunosuppressive therapy, and favorable
      outcomes were obtained in almost all patients. Toxic effects related to
      treatments were minimal.

PMID- 17502469
TI  - Atherosclerotic burden and early mortality in acute ischemic stroke.
AB  - BACKGROUND: The influence that previous clinical expressions of systemic
      atherosclerosis may have on evolution and early mortality in patients with acute
      ischemic stroke is not known. OBJECTIVE: To evaluate the influence that
      atherosclerotic burden (ATB), assessed by a simple clinical scale, has on the 30
      day mortality in patients with first-ever ischemic stroke. DESIGN: Retrospective
      review of case series from a prospective stroke record. An ATB score ranging from
      0 to 2 was created using the history of ischemic heart disease and peripheral
      arterial disease. The impact of this score on the 30-day mortality was analyzed
      by multivariate regression analysis. SETTING: Tertiary university hospital.
      Patients A total of 1527 patients with first-ever ischemic stroke. Main Outcome
      Measure Thirty-day mortality. RESULTS: The 30-day mortality rate was 13.8%.
      Multivariate regression analysis showed an association between the ATB score and
      the 30-day mortality (P<.001). Comparing patients having no previous ATB with
      those with an ATB score of 1 or 2, the odds ratio (OR) for 30-day mortality
      increased from 1.71 (95% confidence interval [CI], 1.06-2.75) for patients with
      an ATB score of 1 to 5.90 (95% CI, 2.48-14.04) for those with an ATB score of 2.
      Age (OR, 1.05; 95% CI, 1.03-1.08), National Institutes of Health Stroke Scale
      score at admission (OR, 1.22; 95% CI, 1.18-1.25), atrial fibrillation (OR, 1.61;
      95% CI, 1.10-2.35), hyperlipidemia as protector (OR, 0.39; 95% CI, 0.25-0.60),
      and glycemia at admission (OR, 1.07; 95% CI, 1.02-1.12) were also predictors of
      30-day mortality. CONCLUSION: Previous symptomatic atherosclerotic disease
      evaluated by a simple clinical score is an independent predictor of early
      mortality in patients with first-ever ischemic stroke.

PMID- 17502470
TI  - Hereditary spastic paraplegia 3A associated with axonal neuropathy.
AB  - OBJECTIVE: To study the frequency and distribution of mutations in SPG3A in a
      large cohort of patients with hereditary spastic paraplegia. DESIGN: We screened
      a large cohort of 182 families and isolated cases with pure or complex hereditary
      spastic paraplegia phenotypes, which were negative for mutations in SPG4.
      RESULTS: In 12 probands (6.6%), we identified 12 different SPG3A mutations (11
      missense and 1 insertion/frameshift) of which 7 were novel and 3 were de novo. We
      found incomplete penetrance in 1 family (G482V). In most cases, SPG3A mutations
      were associated with an early age at onset (mean, 3 y); however, in 1 family
      (R495W mutation), symptoms started later (mean, 14 y) with clear intrafamilial
      variability (8-28 y). Six patients with an SPG3A mutation (F151S, Q191R, M408T,
      G469A, R495W) originating from 5 unrelated families presented with a complex form
      of hereditary spastic paraplegia associated with a neuropathy (17%). Our
      electrophysiological and pathological findings confirmed an axonal sensory-motor
      neuropathy. There was no correlation between the genotype and the presence of a
      neuropathy. CONCLUSIONS: We conclude that mutations in SPG3A represent an
      important cause of patients in the overall hereditary spastic paraplegia
      population. SPG3A is more often associated with a neuropathy than previously
      assumed. Therefore, patients with a bipyramidal syndrome and a neuropathy should
      be screened for mutations in SPG3A.

PMID- 17502471
TI  - Evaluation of cognitive impairment in older adults: combining brief informant and
      performance measures.
AB  - OBJECTIVE: To combine the AD8, a brief informant interview, with performance
      measures to develop a brief screening tool to improve detection of cognitive
      impairment and dementia in general practice. DESIGN: The AD8 was administered to
      informants. Clinicians conducted independent patient evaluations and administered
      the Clinical Dementia Rating Scale and a 30-minute neuropsychological battery.
      Logistic regression was used to determine the best combination of brief tests to
      correctly classify patients as having no dementia, uncertain dementia, or
      dementia. The area under the receiver operator characteristic curve (AUC)
      evaluated the discriminative ability of the combined tests. PATIENTS/SETTING:
      Patients (n = 255) were consecutive referrals to a dementia clinic. Patients had
      a mean +/- SD age of 73.3 +/- 11.3 years, with 13.7 +/- 3.0 (mean +/- SD) years
      of education. The sample was 56% women; 77% of patients were white. Main Outcome
      Measure Dementia classification. RESULTS: A model combining the AD8 interview
      (odds ratio, 1.91; 95% confidence interval, 1.6-2.3) and the Consortium to
      Establish a Registry for Alzheimer Disease 10-item Word List Recall (odds ratio,
      1.43; 95% confidence interval, 1.2-1.7) predicted dementia with 91.5% correct
      classification (AUC = 0.968; 95% confidence interval, 0.93-0.99). A cutoff of 2
      or greater on the AD8 and less than 5 items remembered on the Word List Recall
      was sensitive (94%) and specific (82%). For cognitive impairments not meeting
      dementia criteria, combining AD8 (odds ratio, 2.31; 95% confidence interval, 1.3
      4.0) and Word List Recall (odds ratio, 1.42; 95% confidence interval, 1.1-1.8)
      was most predictive (AUC = 0.91; 95% confidence interval, 0.8-1.0). Using the
      same cutoffs as those used for dementia gave the best combination of sensitivity
      (85%) and specificity (84%). CONCLUSION: Combining the AD8 interview with the
      Word List Recall improves the ability to detect the presence of dementia. The AD8
      can be administered to an informant and, when combined with Word List Recall, is
      a powerful yet brief method of detecting cognitive impairment.

PMID- 17502472
TI  - Patient's rating of cognitive ability: using the AD8, a brief informant
      interview, as a self-rating tool to detect dementia.
AB  - OBJECTIVE: To test the ability of patients to rate their own cognitive ability
      using the AD8 compared with informant and clinician ratings of cognitive status.
      DESIGN, SETTING, AND PATIENTS: The AD8 was administered to 325 consecutive
      participant-informant dyads enrolled in a longitudinal study at Washington
      University School of Medicine between April 4, 2005, and December 15, 2005. The
      number of AD8 items endorsed by the participant was compared with informant
      answers and an independently derived Clinical Dementia Rating. MAIN OUTCOME
      MEASURE: Strength of association was measured with Spearman (rho) and intraclass
      correlation coefficients. Receiver operator characteristic curves assessed the
      discriminative properties of the AD8. RESULTS: The mean age of participants and
      informants was 72.8 years (range, 43-104 years) and 66.4 years (range, 24-101
      years), respectively. The Clinical Dementia Rating was correlated with both
      informant (rho = 0.75, P<.001) and participant (rho = 0.34, P<.001) AD8 scores.
      Participants' AD8 scores had adequate agreement with informants' AD8 scores
      (intraclass correlation coefficient, 0.53; 95% confidence interval, 0.41-0.62)
      and correlated with subjective complaints of memory problems (rho = 0.47, P<.001)
      but not with estimates of symptom duration. The area under the receiver operator
      characteristic curve for the informant AD8 was 0.89 (95% confidence interval,
      0.86-0.93); for the participant AD8, it was 0.78 (95% confidence interval, 0.68
      0.78). CONCLUSIONS: The AD8 is a brief measure that, when completed by an
      informant, differentiates nondemented from demented individuals. We now
      demonstrate that a self-completed AD8 also differentiates nondemented from
      demented individuals, although the utility was better in mildly impaired
      individuals compared with more demented individuals. In the absence of a reliable
      informant, the AD8 may be asked of the participant to gain an understanding of
      their perception of cognitive status.

PMID- 17502473
TI  - Vasculitic neuropathy in a patient with hereditary C1 inhibitor deficiency.
AB  - OBJECTIVE: To report the clinical, pathological, and mutational features of
      hereditary C1 inhibitor (C1INH) deficiency as a cause of isolated vasculitic
      neuropathy. PATIENT: A 35-year-old woman with sensorimotor mononeuritis multiplex
      and facial palsy. RESULTS: The sural nerve biopsy results showed a decrease of
      myelinated fibers with axonal degeneration and severe hypersensitivity
      vasculitis, with deposition of C1q on vessel walls. Mutational analysis of the
      C1INH gene found a new mutation, a heterozygous 2-base pair deletion in exon 8.
      The patient was treated with plasmapheresis and intravenous methylprednisolone,
      followed by oral prednisolone, which resulted in marked improvement. CONCLUSION:
      Hereditary C1INH deficiency should be included in the differential diagnosis of
      nonsystemic vasculitis neuropathy.

PMID- 17502475
TI  - Linezolid-induced posterior reversible leukoencephalopathy syndrome.
AB  - OBJECTIVE: To describe a 71-year-old woman who developed clinical and
      neuroradiological features of posterior reversible leukoencephalopathy syndrome
      with a compromised blood-brain barrier after 5 days of intravenous linezolid
      therapy for an infected hip prosthesis. DESIGN: Case report. SETTING: Academic
      research. MAIN OUTCOME MEASURES: Posterior reversible leukoencephalopathy
      syndrome was documented using serial cranial magnetic resonance imaging, and the
      blood-brain barrier disturbance was demonstrated by contrast enhancement of a
      lesion and by cerebrospinal fluid analysis. RESULTS: Other causes of posterior
      reversible leukoencephalopathy syndrome, such as renal failure, severe
      hypertension, inflammatory syndromes, and infectious diseases of the central
      nervous system, were excluded during hospitalization. After discontinuation of
      linezolid therapy, the patient's condition improved rapidly. CONCLUSION: To our
      knowledge, this is the first report of likely linezolid-induced posterior
      reversible leukoencephalopathy syndrome with an altered blood-brain barrier after
      short-term intravenous therapy.

PMID- 17502476
TI  - A new episodic ataxia syndrome with linkage to chromosome 19q13.
AB  - BACKGROUND: Multiple episodic ataxia phenotypes and genotypes have been
      described. OBJECTIVE: To describe a new episodic ataxia syndrome. DESIGN:
      Genomewide linkage analysis with dense single nucleotide polymorphism arrays.
      SETTING: University clinic. Patients Family with lifelong episodes of ataxia and
      normal interictal examination results. RESULTS: Suggestive linkage (logarithm of
      odds score, 3.27) to a 10-centimorgan region on chromosome 19q13. CONCLUSION: A
      new dominantly inherited episodic ataxia syndrome is linked to chromosome 19q.

PMID- 17502474
TI  - Association of a presenilin 1 S170F mutation with a novel Alzheimer disease
      molecular phenotype.
AB  - OBJECTIVE: To report an ataxic variant of Alzheimer disease expressing a novel
      molecular phenotype. DESIGN: Description of a novel phenotype associated with a
      presenilin 1 mutation. SETTING: The subject was an outpatient who was diagnosed
      at the local referral center. PATIENT: A 28-year-old man presented with
      psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction.
      Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles
      and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the
      cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected. MAIN OUTCOME
      MEASURES: We analyzed the processing of Abeta precursor protein in vitro as well
      as the Abeta species in brain tissue. RESULTS: The PSEN1 S170F mutation induced a
      3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60%
      increase of secreted Abeta precursor protein in transfected cells. Soluble and
      insoluble fractions isolated from brain tissue showed a prevalence of N
      terminally truncated Abeta species ending at both residues 40 and 42. CONCLUSION:
      These findings define a new Alzheimer disease molecular phenotype and support the
      concept that the phenotypic variability associated with PSEN1 mutations may be
      dictated by the Abeta aggregates' composition.

PMID- 17502477
TI  - Intravascular large B-cell lymphoma presenting as cerebellar and cerebral
      infarction.

PMID- 17502478
TI  - Density of the brain, decline of the mind: an atypical case of Fahr disease.

PMID- 17502479
TI  - Stroke caused by human immunodeficiency virus-associated vasculopathy?

PMID- 17502480
TI  - Fluorescence microscopy--avoiding the pitfalls.

PMID- 17502481
TI  - A cell biological perspective on mitochondrial dysfunction in Parkinson disease
      and other neurodegenerative diseases.
AB  - Dysfunction of mitochondria is frequently proposed to be involved in
      neurodegenerative disease. Deficiencies in energy supply, free radical
      generation, Ca(2+) buffering or control of apoptosis, could all theoretically
      contribute to progressive decline of the central nervous system. Parkinson
      disease illustrates how mutations in very different genes finally impinge
      directly or indirectly on mitochondrial function, causing subtle but finally
      fatal dysfunction of dopaminergic neurons. Neurons in general appear more
      sensitive than other cells to mutations in genes encoding mitochondrial proteins.
      Particularly interesting are mutations in genes such as Opa1, Mfn1 and Dnm1l,
      whose products are involved in the dynamic morphological alterations and
      subcellular trafficking of mitochondria. These indicate that mitochondrial
      dynamics are especially important for the long-term maintenance of the nervous
      system. The emerging evidence clearly demonstrates the crucial role of specific
      mitochondrial functions in maintaining neuronal circuit integrity.

PMID- 17502482
TI  - Cooperative mechanisms of mitotic spindle formation.
AB  - Cooperativity is well known to promote the speed of some biochemical reactions by
      accelerating the activity of enzymes. Recent studies have shown that cooperative
      interactions also function during the formation of a complex cellular structure,
      the mitotic spindle. Capture of kinetochores by dynamic astral microtubules was
      originally proposed as the basis of spindle formation. However, mounting evidence
      indicates that a more complex series of events occurs. It is now clear that there
      are multiple microtubule nucleation and capture sites throughout the spindle.
      Kinetochores, centrosomes and microtubules play multiple roles in establishing
      connections between spindle components and integrating them into a common
      structure. These data support a modified search-and-capture model that
      incorporates additional assembly pathways coordinated by a RanGTP gradient.

PMID- 17502483
TI  - A novel mechanism controls the Ca2+ oscillations triggered by activation of
      ascidian eggs and has an absolute requirement for Cdk1 activity.
AB  - Fertilisation in ascidians triggers a series of periodic rises in cytosolic
      Ca(2+) that are essential for release from metaphase I arrest and progression
      through meiosis II. These sperm-triggered Ca(2+) oscillations are switched off at
      exit from meiosis II. Ascidian zygotes provided the first demonstration of the
      positive feedback loop whereby elevated Cdk1 activity maintained these Ca(2+)
      oscillations. Since then it has been reported that Cdk1 sensitises the type I
      inositol trisphosphate [Ins(1,4,5)P(3)] receptor in somatic cells, and that sperm
      triggered Ca(2+) oscillations in mouse zygotes stop because the forming pronuclei
      sequester phospholipase C zeta that was delivered to the egg by the fertilising
      sperm. Here, using enucleation, we demonstrate in ascidian eggs that Ca(2+)
      spiking stops at the correct time in the absence of pronuclei. Sequestration of
      sperm factor is therefore not involved in terminating Ca(2+) spiking for these
      eggs. Instead we found that microinjection of the Cdk1 inhibitor p21 blocked
      Ca(2+) spiking induced by ascidian sperm extract (ASE). However, such eggs were
      still capable of releasing Ca(2+) in response to Ins(1,4,5)P(3) receptor
      agonists, indicating that ASE-triggered Ca(2+) oscillations can stop even though
      the response to Ins(1,4,5)P(3) remained elevated. These data suggest that Cdk1
      activity promotes Ins(1,4,5)P(3) production in the presence of the sperm factor,
      rather than sensitising the Ca(2+) releasing machinery to Ins(1,4,5)P(3). These
      findings suggest a new link between this cell cycle kinase and the Ins(1,4,5)P(3)
      pathway.

PMID- 17502484
TI  - Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for
      efficient cardiovascular regeneration.
AB  - Recent studies have shown that cardiac stem cells (CSCs) from the adult mammalian
      heart can give rise to functional cardiomyocytes; however, the definite surface
      markers to identify a definitive single entity of CSCs and the molecular
      mechanisms regulating their growth are so far unknown. Here, we demonstrate a
      single-cell deposition analysis to isolate individually selected CSCs from adult
      murine hearts and investigate the signals required for their proliferation and
      survival. Clonally proliferated CSCs express stem cell antigen-1 (Sca-1) with
      embryonic stem (ES) cell-like and mesenchymal cell-like characteristics and are
      associated with telomerase reverse transcriptase (TERT). Using a transgene that
      expresses a GFP reporter under the control of the TERT promoter, we demonstrated
      that TERT(GFP)-positive fractions from the heart were enriched for cells
      expressing Sca-1. Knockdown of Sca-1 transcripts in CSCs led to retarded ex vivo
      expansion and apoptosis through Akt inactivation. We also show that ongoing CSC
      proliferation and survival after direct cell-grafting into ischemic myocardium
      require Sca-1 to upregulate the secreted paracrine effectors that augment
      neoangiogenesis and limit cardiac apoptosis. Thus, Sca-1 might be an essential
      component to promote CSC proliferation and survival to directly facilitate early
      engraftment, and might indirectly exert the effects on late cardiovascular
      differentiation after CSC transplantation.

PMID- 17502485
TI  - Contextual role for angiopoietins and TGFbeta1 in blood vessel stabilization.
AB  - We used a 3D in-vitro model of angiogenesis to investigate the effects of
      different growth factors on vessel formation and stabilization in vitro. Vascular
      endothelial growth factor (VEGF) was the only factor that induced the formation,
      elongation and sprouting of capillary-like structures (CLS) by bovine retinal
      capillary endothelial cells (BREC), an effect that was dose-dependent and
      saturable. Basic fibroblast growth factor 2 (FGF2) enhanced capillary formation
      in the presence of VEGF, leading to a more complex network of CLS and a higher
      rate of BrdU incorporation than VEGF alone, indicating that whereas VEGF acts as
      a morphogen, FGF2 is primarily a mitogen. Addition of transforming growth factor
      beta1 (TGFbeta1) to the 3D assay along with VEGF and FGF2, reduced tube formation
      in a dose-dependent manner. When added at the time of cell plating TGFbeta1
      completely suppressed formation of VEGF/FGF2-stimulated CLS. Angiopoietin 1
      (Ang1) prevented regression of the TGFbeta1-induced CLS, an effect that was
      blocked by angiopoietin 2 (Ang2), but required the continuous presence of VEGF.

PMID- 17502486
TI  - EGF induces macropinocytosis and SNX1-modulated recycling of E-cadherin.
AB  - In epithelia, junction proteins are endocytosed for modulation of cell-cell
      adhesion and cell polarity. In response to growth factors, the cell-cell adhesion
      protein E-cadherin is internalized from the cell surface with degradation or
      recycling as potential fates. However, the cellular machinery involved in
      cadherin internalization and recycling remains controversial. Here we
      investigated EGF-induced E-cadherin internalization. EGF stimulation of MCF-7
      cells resulted in Rac1-modulated macropinocytosis of the E-cadherin-catenin
      complex into endosomal compartments that colocalized with EEA1 and the sorting
      nexin, SNX1. Depletion of cellular SNX1 levels by siRNA resulted in increased
      intracellular accumulation and turnover of E-cadherin internalized from the cell
      surface in response to EGF. Moreover, SNX1 was also required for efficient
      recycling of internalized E-cadherin and re-establishment of epithelial adhesion.
      Together, these findings demonstrate a role for SNX1 in retrieval of E-cadherin
      from a degradative endosomal pathway and in membrane trafficking pathways that
      regulate E-cadherin recycling.

PMID- 17502488
TI  - Questionable role of the angiotensin II receptor subtype 1 autoantibody in the
      pathogenesis of preeclampsia.

PMID- 17502489
TI  - Baroreflex sensitivity inversely correlates with ambulatory blood pressure in
      healthy normotensive humans.
AB  - Patients with hypertension have a blunted sensitivity of baroreflex control of
      heart period. In these patients, baroreflex sensitivity is positively related to
      heart rate variability and inversely related to blood pressure variability. We
      hypothesized that this relationship would also be evident in healthy normotensive
      subjects and that individuals with higher baroreflex sensitivity would have lower
      ambulatory 24-hour blood pressure. Twenty-four-hour ambulatory blood pressure and
      heart rate were recorded in 50 healthy, normotensive, nonobese individuals (31
      women and 19 men). The baroreflex was assessed using sequential bolus
      administration of sodium nitroprusside and phenylephrine, and baroreflex
      sensitivity was calculated as the slope of the relation between systolic blood
      pressure and R-R interval during the resulting blood pressure transients.
      Baroreflex sensitivity was inversely correlated to 24-hour average mean arterial
      pressure (R=0.49; P<0.001) and positively related to daytime heart rate
      variability (R=0.33; P=0.02). In contrast, no relationship was found between
      baroreflex sensitivity and 24-hour heart rate or blood pressure variabilities. We
      conclude that the relationship between baroreflex sensitivity and daytime heart
      rate variability was similar to that reported previously in hypertensive
      subjects. Furthermore, the inverse relation between baroreflex sensitivity and
      mean arterial pressure supports the idea that the baroreflex may exert longer
      term effects on blood pressure than thought previously.

PMID- 17502490
TI  - Prevention of stroke and myocardial infarction by amlodipine and Angiotensin
      receptor blockers: a quantitative overview.
AB  - In the present quantitative overview of outcome trials, we investigated the
      efficacy of amlodipine or angiotensin receptor blockers in the prevention of
      stroke and myocardial infarction in patients with hypertension, coronary artery
      disease, or diabetic nephropathy. The analysis included 12 trials of 94 338
      patients. The analysis of trials involving an amlodipine group showed that
      amlodipine provided more protection against stroke and myocardial infarction than
      other antihypertensive drugs, including angiotensin receptor blockers (-19%,
      P<0.0001 and -7%, P=0.03) and placebo (-37%, P=0.06 and -29%, P=0.04). The
      analysis of trials involving an angiotensin receptor blocker group showed
      contrasting results between trials versus amlodipine and trials versus other
      antihypertensive drugs for stroke (+19% versus -25%; P<0.0001) and myocardial
      infarction (+21% versus +1%; P=0.03). The results of 3 trials comparing an
      angiotensin receptor blocker with placebo were neutral (P> or =0.14). The within
      trial between-group difference in achieved systolic pressure ranged from -1.1 to
      +4.7 mm Hg for trials involving an amlodipine group and from -2.8 to +4.0 mm Hg
      for trials involving an angiotensin receptor blocker group. The metaregression
      analysis correlating odds ratios with blood pressure differences showed a
      negative relationship (regression coefficients: -3% to -8%), which reached
      statistical significance (regression coefficient: -6%; P=0.01) for stroke in
      trials involving an amlodipine group. In conclusion, blood pressure differences
      largely accounted for cardiovascular outcome.

PMID- 17502491
TI  - NOX1 deficiency protects from aortic dissection in response to angiotensin II.
AB  - Oxidative stress leads to vascular damage and participates in the pathomechanisms
      of aortic dissection and aneurysm formation. Here we study aortic dissection in
      mice deficient in the superoxide-generating reduced nicotinamide-adenine
      dinucleotide phosphate oxidase NOX1. Seven days of treatment with the
      hypertensive agent angiotensin II (3 mg/kg per day) led to aortic dissection in
      23% of wild-type C57BL/6J mice but in only 4% of NOX1-deficient mice (P=0.05). In
      contrast, treatment of wild-type C57BL/6J mice with the hypertensive agent
      norepinephrine (12 mg/kg per day), did not lead to aortic dissection or sudden
      death, suggesting that hypertension is not sufficient to cause aortic dissection.
      Interestingly, norepinephrine-dependent blood pressure elevations were conserved
      in NOX1-deficient mice, demonstrating that, different from angiotensin II, it
      acts through NOX1-independent hypertensive mechanisms. The resistance of NOX1
      deficient mice to angiotensin II-induced aortic dissection suggests a role for
      NOX1-dependent alterations of the vascular wall. We, therefore, studied gene
      expression and protease/inhibitor equilibrium. cDNA array analysis demonstrated
      differential effects of angiotensin II on gene expression in wild-type and NOX1
      deficient mice. Tissue inhibitor of metalloproteinase 1 was increased both on the
      mRNA and the protein level in aortas from NOX1-deficient mice. Thus, our results
      demonstrate that NOX1 is involved in the mechanisms of angiotensin II-dependent
      aortic dissection. As one underlying mechanism, we have identified NOX1-dependent
      suppression of tissue inhibitor of metalloproteinase 1 expression, which could
      lead to tissue damage through an altered protease/inhibitor balance.

PMID- 17502492
TI  - Validation of renal oxidative metabolism measurement by positron-emission
      tomography.
AB  - Either in research or in clinical practice, the exploration of renal oxidative
      metabolism is limited by the lack of noninvasive measurement. Positron-emission
      tomography using carbon-11 acetate may estimate tissue oxidative metabolism by
      measuring acetate turnover in the Krebs cycle. Although extensively studied in
      cardiology, this method has never been validated for renal oxidative metabolism
      measurement. The aim of this study is the validation of acetate turnover compared
      with the invasive renal oxygen consumption measurement. Renal oxygen consumption
      and tubular sodium reabsorption were measured invasively in 10 anesthetized pigs.
      Simultaneously, acetate turnover was estimated by the clearance of carbon-11
      acetate in the renal cortex, after a 166-MBq injection of carbon-11 acetate.
      Renal oxidative metabolism was measured under various conditions induced by
      mechanical and pharmacological interventions. Renal oxygen consumption and
      acetate turnover varied on a wide range from 0.05 to 0.29 mmol min(-1) (>5-fold)
      and from 0.025 to 0.188 minutes(-1) (>7-fold), respectively. Acetate turnover was
      very significantly correlated with renal oxygen consumption (P<0.0001; R=0.82)
      and tubular sodium reabsorption (P=0.001; R=0.67). This study demonstrates that
      acetate turnover measures renal oxidative metabolism noninvasively and
      quantitatively, consistent with changes in tubular sodium reabsorption. This
      method may be applied to assess oxidative metabolism in animal models and in
      humans.

PMID- 17502493
TI  - Isolated systolic hypertension is characterized by increased aortic stiffness and
      endothelial dysfunction.
AB  - Isolated systolic hypertension is associated with increased cardiovascular risk.
      It is thought to result from large artery stiffening, which is determined by
      structural components within the vasculature but also by functional factors
      including NO and endothelin-1. We hypothesized that endothelial dysfunction would
      account for increased arterial stiffness in patients with isolated systolic
      hypertension. The aim of this study was to investigate the relationship between
      endothelial function and arterial stiffness in these patients along with control
      subjects. We studied 113 subjects: 35 patients with isolated systolic
      hypertension (mean age+/-SD: 68+/-6 years), 30 age-matched control subjects (65+/
      5 years), and 48 young control subjects (37+/-9 years). Aortic pulse wave
      velocity (PWV) was derived by sequential carotid/femoral waveform recordings.
      Conduit artery endothelial function was determined by flow-mediated dilatation.
      Aortic PWV was higher (9.65+/-2.56 m/s versus 8.26+/-0.85 m/s; P=0.009), and flow
      mediated dilatation was lower (2.67+/-1.64% versus 4.79+/-3.1%; P=0.03) in
      patients with isolated systolic hypertension compared with age-matched control
      subjects. Similarly, aortic PWV was also higher, and flow-mediated dilatation
      lower, in older versus young control subjects (8.26+/-0.85 m/s versus 7.09+/-1.01
      m/s and 4.79+/-3.1% versus 6.94+/-2.7%; P=0.004 for both). Overall, aortic PWV
      correlated inversely with flow-mediated dilatation (r=-0.3; P=0.001), which
      remained significant after adjustment for confounding factors (P=0.01). Patients
      with isolated systolic hypertension have higher aortic PWV and decreased
      endothelial function compared with age-matched control subjects. Our results
      suggest that endothelial function contributes significantly to increased arterial
      stiffness in patients with isolated systolic hypertension and with age.

PMID- 17502494
TI  - Influence of acute and chronic mineralocorticoid excess on endothelial function
      in healthy men.
AB  - Aldosterone has rapid nongenomic effects in the human vasculature. However, data
      are not uniform and little is known about chronic effects of aldosterone.
      Therefore, we investigated acute and chronic effects of elevated aldosterone
      levels on endothelial function in the forearm vasculature of healthy men. In a
      first crossover study, the effects of arterial aldosterone infusion in ascending
      doses (3.3 to 55 pmol/min per 1000 mL forearm volume) on forearm blood flow were
      investigated in 8 healthy men (26+/-2 years). In a second study, endothelium
      dependent (acetylcholine; 0.08, 0.275, and 2.75 micromol/min per 1000 mL) and
      endothelium-independent (sodium nitroprusside 0.02 micromol/min per 1000 mL)
      vasodilation and basal nitric oxide formation (forearm blood flow response to
      blockade by N(G)-monomethyl-l-arginine 8 micromol/min per 1000 mL) were tested in
      10 healthy men (age 30+/-5 years) at baseline, during infusion of 55 pmol/1000 mL
      per min aldosterone (acute effects), and after 0.3 mg/d oral fludrocortisone for
      2 weeks (chronic effects) on separate days. Forearm blood flow was assessed by
      venous occlusion plethysmography. No change in forearm blood flow was seen with
      aldosterone infusion alone. Acute coinfusion of aldosterone increased
      vasodilation to sodium nitroprusside by 93% (P<0.01) and to acetylcholine by 60%
      (P=0.14). Response to N(G)-monomethyl-l-arginine did not change. After 2 weeks of
      oral fludrocortisone, response to acetylcholine was enhanced by 72% compared with
      baseline (P=0.03). Additionally, response to N(G)-monomethyl-l-arginine was
      enhanced by 80% compared with baseline (P=0.05). Aldosterone acutely enhances
      vasodilation to exogenous nitric oxide whereas mineralocorticoid excess for 2
      weeks enhances basal nitric oxide bioactivity and improves endothelium dependent,
      nitric oxide-mediated vasodilation in the forearm vasculature of healthy men.

PMID- 17502495
TI  - Arterial chemoreceptors and sympathetic nerve activity: implications for
      hypertension and heart failure.

PMID- 17502497
TI  - Pediatric microbial keratitis in Taiwanese children: a review of hospital cases.
AB  - OBJECTIVE: To study the clinical and microbiological characteristics of pediatric
      microbial keratitis in Taiwan. METHODS: The medical records of 81 eyes with
      microbial keratitis in 78 children aged 16 years or younger who were diagnosed
      and treated at Chang Gung Memorial Hospital, Taipei, Taiwan, from July 1, 1998,
      through December 31, 2002, were retrospectively reviewed. Predisposing factors,
      microbial culture results, clinical course, and visual outcomes were analyzed.
      RESULTS: Predisposing factors were contact lens wear (33 cases [40.7%]), trauma
      (17 cases [21.0%]), ocular disease (12 cases [14.8%]), and systemic disease (9
      cases [11.1%]). Eight of the 33 contact lenses were rigid gas-permeable lenses
      that were worn overnight for orthokeratology. Forty-seven (58.0%) of the 81 eyes
      were culture positive. The most common isolates were Pseudomonas aeruginosa (21
      eyes [44.7%]) and Staphylococcus aureus (9 eyes [19.1%]). Twelve (14.8%) of the
      81 eyes required surgical intervention. Of the 68 eyes that had a best-corrected
      visual acuity available at the last follow-up, 33 eyes achieved best-corrected
      visual acuity of 20/25 or better. CONCLUSIONS: Predisposing factors for pediatric
      infectious keratitis vary with age. In the teenage years, the most predominant
      risk factor is contact lens wear. Infectious keratitis resultant from overnight
      orthokeratology lenses should receive particular attention. Parents of children
      who consider overnight orthokeratology should evaluate the benefit of temporary
      myopia reduction and the risk of infection. Identification of predisposing
      factors and microorganisms may be helpful for early recognition and treatment of
      pediatric microbial keratitis.

PMID- 17502498
TI  - Risk factors for contact lens-related fusarium keratitis: a case-control study in
      Singapore.
AB  - OBJECTIVE: To evaluate the specific contact lens-related or other factors that
      may contribute to the outbreak of Fusarium keratitis. METHODS: A case-control
      study was conducted of Fusarium keratitis in contact lens users in Singapore from
      March 1, 2005, to May 31, 2006, and included 61 patients with Fusarium keratitis
      and 188 population-based and 179 hospital-based control subjects. Interviewers
      asked about contact lens solution use and other risk factors. RESULTS: Patients
      with Fusarium keratitis were more likely to use ReNu contact lens solutions
      (Bausch & Lomb, Rochester, NY) 58 [95.1%] of 61 cases) than were either
      population-based (62 [34.3%] of 181) or hospital-based (50 [30.1%] of 166)
      control subjects. After controlling for age, sex, contact lens hygiene, and other
      factors, the use of ReNu with MoistureLoc significantly increased the risk of
      Fusarium keratitis (odds ratio, 99.3; 95% confidence interval, 18.4-535.4;
      P<.001), and the risk was 5 times higher compared with the risk with use of ReNu
      MultiPlus, a multipurpose solution (odds ratio, 21.5; 95% confidence interval,
      4.0-115.5; P<.001). CONCLUSIONS: The use of ReNu contact lens solutions
      significantly increased the risk of contact lens-related Fusarium keratitis in
      Singapore. Our data support the recall of ReNu MultiPlus from the Singapore
      market and the need for further investigations into the role of ReNu MultiPlus in
      the development of Fusarium keratitis in other populations.

PMID- 17502499
TI  - Optimal optical coherence tomography-based measures in the diagnosis of
      clinically significant macular edema: retinal volume vs foveal thickness.
AB  - OBJECTIVE: To compare optical coherence tomography-based measures of retinal
      thickness and volume as quantitative tests for clinically significant macular
      edema (CSME). DESIGN: Diagnostic validation study. METHODS: Sixty-five eyes with
      diabetic retinopathy underwent stereo photographic and optical coherence
      tomographic examination. Stereo photographs were examined in a masked fashion to
      determine the presence or absence of CSME according to criteria from the Early
      Treatment Diabetic Retinopathy Study. Optical coherence tomography-based
      measurements of central foveal thickness as well as retinal volumes within a
      series of radii of fixation were generated. The main outcome measures were areas
      under receiver operating characteristic curves. Likelihood ratios, sensitivities,
      and specificities for the diagnosis of CSME were also evaluated. RESULTS: Retinal
      volumes within radii of 0.50 mm and 1.11 mm of fixation and central foveal
      thickness were the best variables for discriminating between those with and
      without CSME as evidenced by analysis of receiver operating characteristic
      curves. There were no significant differences among these 3 variables in their
      performance as diagnostic tests for CSME. CONCLUSIONS: Optical coherence
      tomography-based retinal volume and central foveal thickness variables display
      comparable abilities to discriminate between those with and without CSME. Both
      measures may have clinical applications as quantitative diagnostic tests for
      CSME.

PMID- 17502500
TI  - Effect of eccentric and inconsistent fixation on retinal optical coherence
      tomography measures.
AB  - OBJECTIVE: To assess the relative stabilities of optical coherence tomography
      (OCT)-based retinal volume and central foveal thickness measurements in the
      setting of eccentric or inconsistent fixation. METHODS: Ten healthy right eyes
      underwent multiple macular OCT centered at fixation. To model the effect of
      eccentric or inconsistent fixation, OCT was repeated with scan centers precisely
      shifted by 0.50, 1.00, and 1.50 mm in each of 4 directions. At each scan
      location, retinal volumes within a series of radii of the scan center, as well as
      central foveal thickness, were calculated. The main outcome measure was the
      percentage effect of decentered scanning on each OCT-based variable. RESULTS:
      Central foveal thickness was the variable most affected in this model of
      eccentric and inconsistent fixation. This variable demonstrated changes from
      baseline-centered scans of up to 69.4%. Retinal volumes within a radii of the
      scan center measuring 1.11 mm or greater were least affected by decentered
      scanning, demonstrating maximum changes from baseline-centered scans of only
      15.7% (P<.001 vs foveal thickness). CONCLUSION: Optical coherence tomography
      based retinal volume quantification provides a more stable measure than foveal
      thickness in the setting of eccentric or inconsistent fixation as may occur in
      the setting of macular pathologic conditions.

PMID- 17502501
TI  - Sweep visual evoked potential testing as a predictor of recognition acuity in
      albinism.
AB  - OBJECTIVE: To determine if sweep visual evoked potential (VEP) acuity is
      predictive of recognition acuity in children with albinism. METHODS: A
      retrospective review was performed in children with albinism who underwent sweep
      VEP testing from 1992 to 2003. All patients had a complete ophthalmologic
      examination with either binocular or monocular sweep VEP testing and at least 5
      years of follow-up. Positive predictability of sweep VEP acuity was defined as
      final recognition acuity within 1 Snellen line of initial sweep VEP acuity.
      RESULTS: Of the 13 patients included in the study, 11 had nystagmus, iris
      transillumination defects, and foveal hypoplasia at initial examination. The mean
      age at initial sweep VEP testing was 3.1 years (range, 0.1-10.0 years). Five of
      13 patients had initial sweep VEP acuity that was predictive of final recognition
      acuity. Five additional patients had final recognition acuity, which surpassed
      initial sweep VEP acuity by 2 to 3 lines. Of these 10 patients, the mean duration
      for recognition acuity to reach VEP acuity was 5.4 years. There was no
      correlation between predictive VEP acuity and foveal pigmentation, refractive
      error, strabismus, nystagmus, or longer follow-up. CONCLUSIONS: Sweep VEP testing
      can be used as a predictive tool for recognition acuity in children with
      albinism. Predictability was found in a clinical spectrum of albinism.

PMID- 17502502
TI  - A 10-year overview of double elevator muscle weakening procedures.
AB  - OBJECTIVE: To report the effect of weakening the superior rectus and inferior
      oblique (IO) muscles on ocular rotations. DESIGN: Observational case series. We
      reviewed a 10-year period of medical records of consecutive patients who
      underwent bilateral 5- to 11-mm (mean, 8.0 mm; SD, 1.1 mm) superior rectus muscle
      recessions combined with an IO muscle recession, myectomy, or anterior
      transposition. The effects on ocular rotations and eyelid position were recorded
      for the 37 patients (69 eyes) who were followed up for at least 6 months
      postoperatively. Nonparametric 1-way analysis of variance was used to compare
      results across the 3 procedures. The setting was a subspecialty practice at an
      academic institution. RESULTS: Supraduction deficiency was significantly
      associated with transposition of the IO muscle anterior to the inferior rectus
      muscle insertion compared with the standard IO muscle recession (P = .001), and
      IO muscle myectomy (P = .009). Y-pattern exotropia occurred more frequently after
      transposition of the IO muscle anterior to the inferior rectus muscle insertion
      than other weakening procedures (P<.001). CONCLUSION: Transposition of the IO
      muscle anterior to the inferior rectus muscle insertion, combined with
      ipsilateral superior rectus muscle recession, results in more supraduction
      deficiency and more frequent Y-pattern exotropia compared with standard IO muscle
      recession.

PMID- 17502503
TI  - Human retinal pigment epithelium cell changes and expression of alphaB
      crystallin: a biomarker for retinal pigment epithelium cell change in age-related
      macular degeneration.
AB  - OBJECTIVE: To examine changes in the retinal pigment epithelium (RPE) in eyes
      with age-related macular degeneration (AMD) and specifically to characterize
      alphaB-crystallin expression in RPE cells as a biomarker in this disease.
      METHODS: Maculae from human patients diagnosed as having AMD or from age-matched
      control eyes were isolated, cryosectioned, and analyzed immunohistochemically for
      alphaB-crystallin and for cell type-specific markers. RESULTS: In eyes with dry
      and wet AMD, alphaB-crystallin was heterogeneously expressed by a subpopulation
      of RPE cells in the macular region (frequently in cells adjacent to drusen) and
      in areas of RPE hypertrophy associated with wet AMD. In contrast, alphaB
      crystallin was not detected at significant levels in control RPE. CONCLUSION:
      Accompanying the formation of drusen in early-stage and late-stage AMD, RPE cells
      undergo change to express alphaB-crystallin. CLINICAL RELEVANCE: The detection of
      alphaB-crystallin in the RPE of patients with early and advanced AMD implicates
      this as an AMD biomarker. Sporadic expression of alphaB-crystallin by RPE cells
      localized adjacent to drusen in early AMD indicates that changes in the gene
      expression of RPE cells accompany early stages of the disease and introduces
      novel potential targets for AMD therapy.

PMID- 17502504
TI  - Effect of Smad7 gene overexpression on transforming growth factor beta-induced
      retinal pigment fibrosis in a proliferative vitreoretinopathy mouse model.
AB  - OBJECTIVE: To determine the effects of Smad7 gene transfer in the prevention of
      fibrogenic responses by the retinal pigment epithelium, a major cause of
      proliferative vitreoretinopathy after retinal detachment, in mice. METHODS:
      Retinal detachment-induced proliferative vitreoretinopathy in a mouse model.
      Forty-eight eyes received either an adenoviral gene transfer of Smad7 or Cre
      recombinase gene only. The eyes were histologically analyzed. A retinal pigment
      epithelial cell line, ARPE-19, was used to determine whether Smad7 gene
      transfection suppresses the fibrogenic response to transforming growth factor
      (TGF) beta2 exposure. RESULTS: The Smad7 gene transfer inhibited TGF-beta2/Smad
      signaling in ARPE-19 cells and expression of collagen type I and TGF-beta1 but
      had no effect on their basal levels. In vivo Smad7 overexpression resulted in
      suppression of Smad2/3 signals and of the fibrogenic response to epithelial
      mesenchymal transition by the retinal pigment epithelium. CONCLUSION: Smad7 gene
      transfer suppresses fibrogenic responses to TGF-beta2 by retinal pigment
      epithelial cells in vitro and in vivo. Clinical Relevance Smad7 gene transfer
      might be a new strategy to prevent and treat proliferative vitreoretinopathy.

PMID- 17502505
TI  - Stability of visual acuity improvement following discontinuation of amblyopia
      treatment in children aged 7 to 12 years.
AB  - OBJECTIVE: To assess the stability of visual acuity improvement during the first
      year after cessation of amblyopia treatment other than spectacle wear in children
      aged 7 to 12 years. METHODS: At the completion of a multicenter randomized trial
      during which amblyopia treated with patching and atropine improved by at least 2
      lines on the electronic Early Treatment of Diabetic Retinopathy Study testing
      protocol, 80 patients aged 7 to 12 years were followed up while not receiving
      treatment (other than spectacle wear) for 1 year. MAIN OUTCOME MEASURE: Ten
      letters or more (> or =2 lines) worsening of visual acuity (measured using the
      electronic Early Treatment of Diabetic Retinopathy Study testing protocol) during
      the year following treatment discontinuation. RESULTS: During the year following
      cessation of treatment, the cumulative probability of worsening visual acuity (>
      or =2 lines) was 7% (95% confidence interval, 3%-17%); 82% of patients maintained
      an increase in visual acuity of 10 letters or more compared with their visual
      acuity before starting treatment. CONCLUSION: Visual acuity improvement occurring
      during amblyopia treatment is sustained in most children aged 7 to 12 years for
      at least 1 year after discontinuing treatment other than spectacle wear. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT00094692.

PMID- 17502506
TI  - Association between vitamin D and age-related macular degeneration in the Third
      National Health and Nutrition Examination Survey, 1988 through 1994.
AB  - OBJECTIVE: To evaluate the associations between levels of vitamin D (25
      hydroxyvitamin D) in serum and prevalent age-related macular degeneration (AMD).
      METHODS AND DESIGN: Cross-sectional associations of serum vitamin D and early and
      advanced AMD, assessed from nonmydriatic fundus photographs, were evaluated in
      the third National Health and Nutrition Examination Survey, a multistage
      nationally representative probability sample of noninstitutionalized individuals
      (N = 7752; 11% with AMD). RESULTS: Levels of serum vitamin D were inversely
      associated with early AMD but not advanced AMD. The odds ratio (OR) and 95%
      confidence interval (CI) for early AMD among participants in the highest vs
      lowest quintile of serum vitamin D was 0.64 (95% CI, 0.5-0.8; P trend <.001).
      Exploratory analyses were conducted to evaluate associations with important food
      and supplemental sources of vitamin D. Milk intake was inversely associated with
      early AMD (OR, 0.75; 95% CI, 0.6-0.9). Fish intake was inversely associated with
      advanced AMD (OR, 0.41; 95% CI, 0.2-0.9). Consistent use vs nonuse of vitamin D
      from supplements was inversely associated with early AMD only in individuals who
      did not consume milk daily (early AMD: OR, 0.67; 95% CI, 0.5-0.9). CONCLUSION:
      This study provides evidence that vitamin D may protect against AMD. Additional
      studies are needed to confirm these findings.

PMID- 17502507
TI  - The relationship of dietary lipid intake and age-related macular degeneration in
      a case-control study: AREDS Report No. 20.
AB  - OBJECTIVE: To evaluate the association of lipid intake with baseline severity of
      age-related macular degeneration (AMD) in the Age-Related Eye Disease Study
      (AREDS). METHODS: Age-Related Eye Disease Study participants aged 60 to 80 years
      at enrollment (N = 4519) provided estimates of habitual nutrient intake through a
      self-administered semiquantitative food frequency questionnaire. Stereoscopic
      color fundus photographs were used to categorize participants into 4 AMD severity
      groups and a control group (participants with <15 small drusen). RESULTS: Dietary
      total omega-3 long-chain polyunsaturated fatty acid (LCPUFA) intake was inversely
      associated with neovascular (NV) AMD (odds ratio [OR], 0.61; 95% confidence
      interval [CI], 0.41-0.90), as was docosahexaenoic acid, a retinal omega-3 LCPUFA
      (OR, 0.54; 95% CI, 0.36-0.80), comparing highest vs lowest quintile of intake,
      after adjustment for total energy intake and covariates. Higher fish consumption,
      both total and broiled/baked, was also inversely associated with NV AMD (OR,
      0.61; 95% CI, 0.37-1.00 and OR, 0.65; 95% CI, 0.45-0.93, respectively). Dietary
      arachidonic acid was directly associated with NV AMD prevalence (OR, 1.54; 95%
      CI, 1.04-2.29). No statistically significant relationships existed for the other
      lipids or AMD groups. CONCLUSION: Higher intake of omega-3 LCPUFAs and fish was
      associated with decreased likelihood of having NV AMD.

PMID- 17502508
TI  - Snare technique for enucleation of eyes with advanced retinoblastoma.
AB  - Retrospective analysis of surgical outcomes for enucleation in pediatric
      retinoblastoma stage 5B using the snare wire loop (n = 55) and standard curved
      enucleation scissors (n = 22) revealed that a statistically significant longer
      mean optic nerve length was obtained with the snare (13.35 mm) compared with
      scissors (11.05 mm; P = .005). Four scissor cases had prolonged bleeding and
      required thrombin (18.2%), but no snare cases had difficulty with hemostasis (P =
      .005). More crush artifact was seen with the snare than with scissors (P<.001),
      but this did not affect the ability to determine tumor involvement at the
      surgical margin. The enucleation snare should be considered a valuable surgical
      instrument in the small pediatric orbit since obtaining the longest optic nerve
      segment has prognostic implications in retinoblastoma.

PMID- 17502509
TI  - Use of our existing eye care human resources: assessment of the productivity of
      cataract surgeons trained in eastern Africa.
AB  - OBJECTIVES: To measure the productivity of cataract surgeons in Africa and assess
      the factors that predict high productivity. METHODS: A questionnaire on
      productivity and working environments was sent to all cataract surgeons trained
      in Malawi, Uganda, Tanzania, and Kenya. In addition, 2 meetings and in-depth
      discussions were held to elicit information on strategies to improve productivity
      among surgeons in general. RESULTS: More than 77 000 cataract surgeries were
      performed in the years 2000 through 2004, resulting in an annual productivity
      rate of 243 surgeries per surgeon. Higher productivity was associated with having
      2 or more cataract surgical sets, a well-functioning operating microscope, 3 or
      more nursing support staff, and a community program that includes transporting
      patients to the hospital. CONCLUSION: Strategies for training, supporting, and
      supervising cataract surgeons in Africa need to be revised to create conditions
      amenable to greater productivity.

PMID- 17502510
TI  - Overnight orthokeratology and corneal infection risk in children.

PMID- 17502511
TI  - The Nobel Prize of 1906.
AB  - December 2006 marked 100 years since the Nobel Prize in Physiology or Medicine
      was awarded jointly to 2 pioneers in the cellular anatomy of the central nervous
      system (CNS), Camillo Golgi and Santiago Ramon y Cajal. Golgi developed the
      silver impregnation method for studying nerve cells, a technique that clearly
      showed entire cells with their arborizing dendrites and axons for the first time.
      Ramon y Cajal seized on the method for a series of groundbreaking studies that
      provided convincing support for what came to be known as the neuron theory, in
      opposition to the reigning model of the time, the reticular theory. The retina
      was one of Ramon y Cajal's favorite tissues for study. Although he was perplexed
      by the horizontal and amacrine cells, he was remarkably prescient in his analysis
      of retinal and CNS cellular anatomy. Few scientists have cast such a long shadow
      in their field, but Ramon y Cajal did not establish the neuron theory single
      handedly, and the real tale is much more complicated.

PMID- 17502512
TI  - A curious letter in the archives: Jonas Friedenwald and the new Duke University
      School of Medicine.

PMID- 17502513
TI  - Decompression retinopathy after 25-gauge transconjunctival sutureless vitrectomy:
      report of 2 cases.

PMID- 17502514
TI  - Ocular trauma from nail gun cartridge wire.

PMID- 17502515
TI  - Avellino dystrophy in a patient after laser-assisted in situ keratomileusis
      surgery manifesting as granular dystrophy.

PMID- 17502516
TI  - Minocycline for the treatment of ocular and ocular adnexal sarcoidosis.

PMID- 17502517
TI  - Paclitaxel maculopathy.

PMID- 17502518
TI  - Optic disc tuber.

PMID- 17502519
TI  - Lymphomatoid granulomatosis associated with bilateral exudative retinal
      detachments.

PMID- 17502520
TI  - Autofluorescence imaging in a case of benign familial fleck retina.

PMID- 17502521
TI  - Ultrasonographic signs in complete optic nerve avulsion.

PMID- 17502523
TI  - Reduced ocular allergy with fixed-combination 0.2% brimonidine-0.5% timolol.

PMID- 17502524
TI  - Through a yellow glass darkly.

PMID- 17502525
TI  - Phosphorus comes of age as a cardiovascular risk factor.

PMID- 17502526
TI  - Obesity and mortality: watch your waist, not just your weight.

PMID- 17502527
TI  - Guidelines and consensus statements regarding the conduction and reporting of
      clinical research studies.

PMID- 17502528
TI  - Relations of serum phosphorus and calcium levels to the incidence of
      cardiovascular disease in the community.
AB  - BACKGROUND: Higher levels of serum phosphorus and the calcium-phosphorus product
      are associated with increased mortality from cardiovascular disease (CVD) in
      patients with chronic kidney disease (CKD) or prior CVD. However, it is unknown
      if serum phosphorus levels influence vascular risk in individuals without CKD or
      CVD. METHODS: We prospectively evaluated 3368 Framingham Offspring study
      participants (mean age, 44 years; 51% were women) free of CVD and CKD. We used
      multivariable Cox models to relate serum phosphorus and calcium levels to CVD
      incidence. RESULTS: On follow-up (mean duration, 16.1 years), there were 524
      incident CVD events (159 in women). In multivariable analyses and adjusting for
      established risk factors and additionally for glomerular filtration rate and for
      hemoglobin, serum albumin, proteinuria, and C-reactive protein levels, a higher
      level of serum phosphorus was associated with an increased CVD risk in a
      continuous fashion (adjusted hazard ratio per increment of milligrams per
      deciliter, 1.31; 95% confidence interval, 1.05-1.63; P=.02; P value for trend
      across quartiles = .004). Individuals in the highest serum phosphorus quartile
      experienced a multivariable-adjusted 1.55-fold CVD risk (95% confidence interval,
      1.16%-2.07%; P=.004) compared with those in the lowest quartile. These findings
      remained robust in time-dependent models that updated CVD risk factors every 4
      years and in analyses restricted to individuals without proteinuria and an
      estimated glomerular filtration rate greater than 90 mL/min per 1.73 m(2). Serum
      calcium was not related to CVD risk. CONCLUSION: Higher serum phosphorus levels
      are associated with an increased CVD risk in individuals free of CKD and CVD in
      the community. These observations emphasize the need for additional research to
      elucidate the potential link between phosphorus homeostasis and vascular risk.

PMID- 17502529
TI  - Abdominal adiposity and mortality in Chinese women.
AB  - BACKGROUND: Increased abdominal adiposity has been linked to an increase in
      mortality in populations where many are overweight or obese; it is unclear
      whether the same is true in relatively lean populations. METHODS: We examined the
      association between waist-hip ratio and mortality in the Shanghai Women's Health
      Study, a population-based, prospective cohort study of Chinese women aged 40 to
      70 years enrolled from December 28, 1996, through May 23, 2000, 95% of whom had a
      body mass index (calculated as weight in kilograms divided by height in meters
      squared) of less than 30.0. Included in this analysis were 72 773 nonsmoking
      women who had anthropometrics taken by trained interviewers at enrollment and who
      were followed up through December 31, 2004. Deaths were ascertained by biennial
      home visits and linkage with the vital statistics registry. RESULTS: During a
      mean follow-up of 5.7 years, 1456 deaths occurred. The waist-hip ratio was
      positively and significantly associated with deaths from all causes,
      cardiovascular disease, and diabetes (P<.01 for trend). A less significant
      positive association was found for death from cancer. After adjustment for body
      mass index and other potential confounders, the relative risks of total mortality
      were 1 (reference group), 1.28 (95% confidence interval [CI], 1.04-1.58), 1.40
      (95% CI, 1.14-1.72), 1.54 (95% CI, 1.26-1.88), and 1.95 (95% CI, 1.60-2.38)
      across the lowest to the highest waist-hip ratio quintiles. The positive
      association appeared to be more evident in women with a lower body mass index.
      The relative risks of total mortality comparing the extreme waist-hip ratio
      quintiles were 2.36 (95% CI, 1.71-3.27), 1.60 (95% CI, 1.10-2.34), and 1.46 (95%
      CI, 0.97-2.20) for women with a body mass index of less than 22.3, 22.3 to 25.1,
      and 25.2 or greater, respectively. CONCLUSION: Abdominal adiposity independently
      predicts mortality risk, particularly for nonobese women.

PMID- 17502530
TI  - Calcium plus vitamin D supplementation and the risk of postmenopausal weight
      gain.
AB  - BACKGROUND: Obesity in the United States has increased significantly during the
      past several decades. The role of calcium in the maintenance of a healthy body
      weight remains controversial. METHODS: A randomized, double-blinded, placebo
      controlled trial was performed with 36 282 postmenopausal women, aged 50 to 79
      years, who were already enrolled in the dietary modification and/or hormone
      therapy arms of the Women's Health Initiative clinical trial. Women were
      randomized at their first or second annual visit to receive a dose of 1000 mg of
      elemental calcium plus 400 IU of cholecalciferol (vitamin D) or placebo daily.
      Change in body weight was ascertained annually for an average of 7 years.
      RESULTS: Women receiving calcium plus cholecalciferol supplements vs women
      receiving placebo had a minimal but consistent favorable difference in weight
      change (mean difference, -0.13 kg; 95% confidence interval, -0.21 to -0.05; P =
      .001). After 3 years of follow-up, women with daily calcium intakes less than
      1200 mg at baseline who were randomized to supplements were 11% less likely to
      experience small weight gains (1-3 kg) and 11% less likely to gain more moderate
      amounts of weight (>3 kg) (P for interaction for baseline calcium intake = .008).
      CONCLUSION: Calcium plus cholecalciferol supplementation has a small effect on
      the prevention of weight gain, which was observed primarily in women who reported
      inadequate calcium intakes. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00000611.

PMID- 17502531
TI  - Sex differences in perceived risks, distrust, and willingness to participate in
      clinical trials: a randomized study of cardiovascular prevention trials.
AB  - BACKGROUND: Multiple sex differences exist in cardiovascular disease burden and
      treatment efficacies; adequate participation of both sexes is crucial to clinical
      research. METHODS: A multicenter, double-blind, randomized study evaluated sex
      and trial scenarios on willingness to participate (WTP) in cardiovascular
      prevention trials and examined sex differences in perceived risks and distrust.
      Hypothetical trial scenarios randomized multifactorial vignettes of adverse
      effects, trial durations, sponsors, financial incentives, and conflicts of
      interest. RESULTS: With 783 participants across 13 clinical centers, women showed
      lower distrust of medical researchers, perceived greater risk of myocardial
      infarction, and perceived greater risk of harm from trial participation than men.
      Men had 15% greater WTP than women (33.1% vs 28.7%; relative risk [RR], 1.15; 95%
      confidence interval [CI], 1.02-1.31); adjusting for explanatory mediators, we
      found that sex differences in perceived risks and benefits explained the sex gap
      in WTP. Although greater perceived probability of harm (RR, 0.41; 95% CI, 0.23
      0.72), health benefit (RR, 2.99; 95% CI, 1.63-5.46), and quality of care (RR,
      1.71; 95% CI, 1.12-2.61) strongly predicted WTP (for perceived probabilities
      >or=80% vs <20%) similarly in both sexes, and perceptions of distrust and
      myocardial infarction risk predicted WTP differently between sexes (P<or=.01 for
      interactions), age, history of coronary artery disease, hypertension, and
      diabetes mellitus increased WTP in men but not in women (P<or=.05 for sex
      interactions). Compared with no financial conflict, disclosure of investigator
      patent ownership increased WTP in women, while it decreased WTP in men (P=.02 for
      sex interaction). Monetary incentives were overall more effective on WTP in women
      (P=.03 for sex interaction). CONCLUSIONS: In this multicenter study, women
      perceived greater risk of harm and myocardial infarction and showed lower WTP in
      cardiovascular prevention trials. Evidence underscores the importance of sex in
      influencing clinical trial enrollment.

PMID- 17502532
TI  - Outcomes of myocardial infarction in hospitals with percutaneous coronary
      intervention facilities.
AB  - BACKGROUND: Despite evidence on the efficacy and safety of percutaneous coronary
      intervention (PCI) for patients with acute myocardial infarction, it is unclear
      whether patients admitted to hospitals with on-site PCI facilities (herein after,
      PCI hospitals) have improved outcomes in routine practice. METHODS: We compared
      processes of care, hospital outcomes, and 1-year mortality rate for 1176
      consecutive patients admitted to 126 PCI hospitals and 738 patients admitted to
      190 non-PCI hospitals in France from November 1 to November 30, 2000. RESULTS:
      Patients admitted to PCI hospitals were more likely to receive evidence-based
      acute (within 48 hours of admission) and discharge medications and to undergo PCI
      within 48 hours of admission than those admitted to non-PCI hospitals (54% vs
      6.2%; P<.001). Despite comparable rates of in-hospital stroke (0.9% vs 1.1%;
      P=.75) and reinfarction (1.7% vs 2.5%; P=.25), patients admitted to PCI vs non
      PCI hospitals had lower in-hospital (7.5% vs 12%; P=.001) and 1-year (13% vs 20%;
      P<.001) mortality rates. Admission to PCI hospitals was associated with decreased
      hazard ratios of mortality after adjusting for baseline characteristics (0.75;
      95% confidence interval, 0.57-0.98) or propensity score (0.76; 95% confidence
      interval, 0.59-0.97). Most of the survival benefit of admission to a PCI hospital
      was explained by the use of PCI and evidence-based discharge medications.
      CONCLUSIONS: In this prospective observational study, admission of patients with
      acute myocardial infarction to PCI hospitals was associated with greater use of
      PCI and evidence-based medications and with improved 1-year survival. Although we
      cannot exclude the possibility that some unmeasured confounding factors might
      explain the survival benefit of admission to PCI hospitals, our findings support
      routine use of PCI and evidence-based medications for these patients.

PMID- 17502533
TI  - Longitudinal incidence and prevalence of adverse outcomes of diabetes mellitus in
      elderly patients.
AB  - BACKGROUND: The natural history of type 2 diabetes mellitus (DM) in the elderly
      has not been previously described in a national longitudinal sample. METHODS:
      This national longitudinal analysis (January 1, 1991, to December 31, 2004)
      examines mortality and morbidity rates in a representative sample of elderly
      patients newly diagnosed as having DM. Medicare beneficiaries diagnosed as having
      DM in 1994 (n=33,772) were compared with a control group (n=25,563) regarding
      death, lower extremity complications, nephropathy, retinopathy, cardiovascular
      complications, and cerebrovascular complications. RESULTS: The DM group had
      excess mortality of 9.2% by year 11 compared with the control group. By 2004,
      91.8% of the DM group experienced an adverse complication compared with 72.0% of
      the control group. The DM group had a higher prevalence and incidence of
      microvascular and macrovascular complications at all time points compared with
      controls. Patients with DM were at increased risk for all lower extremity
      complications, particularly those requiring surgical intervention (gangrene,
      debridement, and amputation). Cardiovascular complications were a leading cause
      of morbidity, with 57.6% of the DM group diagnosed as having heart failure
      compared with 34.1% of the controls. CONCLUSION: Elderly persons newly diagnosed
      as having DM experienced high rates of complications during 10-year follow-up,
      far in excess of elderly persons without this diagnosis, implying a substantial
      burden on the individual and on the health care system.

PMID- 17502534
TI  - Association between serum free thyroxine concentration and atrial fibrillation.
AB  - BACKGROUND: Previous studies have suggested that minor changes in thyroid
      function are associated with risk of atrial fibrillation (AF). Our objective was
      to determine the relationship between thyroid function and presence of atrial
      fibrillation (AF) in older subjects. METHODS: A population-based study of 5860
      subjects 65 years and older, which excluded those being treated for thyroid
      dysfunction and those with previous hyperthyroidism. Main outcome measures
      included tests of thyroid function (serum free thyroxine [T(4)] and thyrotropin
      [TSH]) and the presence of AF on resting electrocardiogram. RESULTS: Fourteen
      subjects (0.2%) had previously undiagnosed overt hyperthyroidism and 126 (2.2%),
      subclinical hyperthyroidism; 5519 (94.4%) were euthyroid; and 167 (2.9%) had
      subclinical hypothyroidism and 23 (0.4%), overt hypothyroidism. The prevalence of
      AF in the whole cohort was 6.6% in men and 3.1% in women (odds ratio, 2.23;
      P<.001). After adjusting for sex, logistic regression showed a higher prevalence
      of AF in those with subclinical hyperthyroidism compared with euthyroid subjects
      (9.5% vs 4.7%; adjusted odds ratio, 2.27; P=.01). Median serum free T(4)
      concentration was higher in those with AF than in those without (1.14 ng/dL;
      interquartile range [IQR], 1.05-1.27 ng/dL [14.7 pmol/L; IQR, 13.5-16.4 pmol/L]
      vs 1.10 ng/dL; IQR, 1.00-1.22 ng/dL [14.2 pmol/L; IQR, 12.9-15.7 pmol/L];
      P<.001), and higher in those with AF when analysis was limited to euthyroid
      subjects (1.13 ng/dL; IQR, 1.05-1.26 ng/dL [14.6 pmol/L; IQR, 13.5-16.2 pmol/L]
      vs 1.10 ng/dL; IQR, 1.01-1.21 ng/dL [14.2 pmol/L; IQR, 13.0-15.6 pmol/L];
      P=.001). Logistic regression showed serum free T(4) concentration, increasing
      category of age, and male sex all to be independently associated with AF. Similar
      independent associations were observed when analysis was confined to euthyroid
      subjects with normal TSH values. CONCLUSIONS: The biochemical finding of
      subclinical hyperthyroidism is associated with AF on resting electrocardiogram.
      Even in euthyroid subjects with normal serum TSH levels, serum free T(4)
      concentration is independently associated with AF.

PMID- 17502535
TI  - Risk factors and short-term mortality of venous thromboembolism diagnosed in the
      primary care setting in the United Kingdom.
AB  - BACKGROUND: Venous thromboembolism (VTE) manifesting as deep vein thrombosis
      (DVT) and pulmonary embolism (PE) remains a common vascular disease with high
      mortality and morbidity. Our aim was to study the clinical spectrum of VTE,
      assess its incidence in the general population, and evaluate potential risk
      factors. METHODS: Prospective cohort study with nested case-control analysis
      using the General Practice Research Database (1994-2000). Venous thromboembolism
      was newly diagnosed in 6550 patients. Cases were compared with a random sample of
      10,000 controls and frequency-matched by age, sex, and year. RESULTS: The
      incidence rate of VTE was 74.5 per 100,000 person-years. Overweight, varicose
      veins, inflammatory bowel disease, cancer, and oral corticosteroid use were
      associated with a greater risk of VTE. Ischemic heart disease, heart failure, and
      cerebrovascular diseases were associated with an increased risk of PE but not
      with DVT. Venous thromboembolism was strongly associated with fractures (odds
      ratio [OR], 21.3; 95% confidence interval [CI], 15.7-28.9) and surgery (OR, 25.0;
      95% CI, 14.4-43.5). In women, the risk of VTE was 1.9 (95% CI, 1.5-2.3) among
      those receiving opposed hormone therapy (in which the woman takes estrogen
      throughout the month and progesterone for 10-14 days later in the month) and 1.9
      (95% CI, 1.4-2.5) among those taking oral contraceptives. Cancer and
      cerebrovascular diseases presented a greater relative risk of fatal PE compared
      with nonfatal PE. CONCLUSIONS: Overweight, varicose veins, cancer, inflammatory
      bowel disease, fractures, surgery, and use of oral corticosteroids, oral
      contraceptives, and opposed hormone therapy were independent risk factors for
      both DVT and PE. The magnitude of the association with some risk factors varied
      between DVT and PE, as well as between fatal and nonfatal PE.

PMID- 17502536
TI  - A comparison of Internet and print-based physical activity interventions.
AB  - BACKGROUND: Physical activity interventions tailored to individual
      characteristics and delivered via print produce greater increases in activity
      compared with nontailored interventions and controls. Using the Internet to
      deliver a tailored physical activity intervention offers an alternative to print
      that might be available to larger populations at a lower cost. METHODS:
      Participants (N=249 adults; mean [SD] age, 44.5 [9.3] years; and mean [SD] body
      mass index [calculated as weight in kilograms divided by height in meters
      squared], 29.4 [6.1]) were randomized to 1 of 3 physical activity interventions:
      (1) motivationally tailored Internet (tailored Internet, n=81), (2)
      motivationally tailored print (tailored print, n=86); and (3) 6 researcher
      selected Web sites available to the public (standard Internet, n=82).
      Participants in the tailored Internet and tailored print arms received the same
      tailored intervention content. Participants were assessed at baseline and at 6
      and 12 months. RESULTS: At 6 months, participants in the tailored print arm
      reported a median of 112.5 minutes of physical activity per week, those in the
      tailored Internet arm reported 120.0 minutes, and those in the standard Internet
      arm reported 90.0 minutes (P=.15). At 12 months, the physical activity minutes
      per week were 90.0, 90.0, and 80.0 for those in the tailored print, tailored
      Internet, and standard Internet arms, respectively (P=.74). Results indicated no
      significant differences between the 3 arms. CONCLUSIONS: The use of tailored
      Internet, tailored print, and standard Internet as part of a behavior change
      program increased physical activity behavior similarly. Because the use of the
      Internet was not different from the print-based intervention, this may be an
      opportunity to reach more sedentary adults in a more cost-effective way. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00200317.

PMID- 17502537
TI  - Use of proton pump inhibitors and the risk of community-acquired pneumonia: a
      population-based case-control study.
AB  - BACKGROUND: Recently, the use of proton pump inhibitors (PPIs) has been
      associated with an increased risk of pneumonia. We aimed to confirm this
      association and to identify the risk factors. METHODS: We conducted a population
      based case-control study using data from the County of Funen, Denmark. Cases
      (n=7642) were defined as all patients with a first-discharge diagnosis of
      community-acquired pneumonia from a hospital during 2000 through 2004. We also
      selected 34 176 control subjects, who were frequency matched to the cases by age
      and sex. Data on the use of PPIs and other drugs, on microbiological samples, on
      x-ray examination findings, and on comorbid conditions were extracted from local
      registries. Confounders were controlled by logistic regression. RESULTS: The
      adjusted odds ratio (OR) associating current use of PPIs with community-acquired
      pneumonia was 1.5 (95% confidence interval [CI], 1.3-1.7). No association was
      found with histamine(2)-receptor antagonists (OR, 1.10; 95% CI, 0.8-1.3) or with
      past use of PPIs (OR, 1.2; 95% CI, 0.9-1.6). Recent initiation of treatment with
      PPIs (0-7 days before index date) showed a particularly strong association with
      community-acquired pneumonia (OR, 5.0; 95% 2.1-11.7), while the risk decreased
      with treatment that was started a long time ago (OR, 1.3; 95% CI, 1.2-1.4).
      Subgroup analyses revealed high ORs for users younger than 40 years (OR, 2.3; 95%
      CI, 1.3-4.0). No dose-response effect could be demonstrated. CONCLUSION: The use
      of PPIs, especially when recently begun, is associated with an increased risk of
      community-acquired pneumonia.

PMID- 17502538
TI  - Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study
      and meta-analysis.
AB  - BACKGROUND: Prospective studies on fiber and magnesium intake and risk of type 2
      diabetes mellitus were inconsistent. We examined associations between fiber and
      magnesium intake and risk of type 2 diabetes and summarized existing prospective
      studies by meta-analysis. METHODS: We conducted a prospective cohort study of
      9702 men and 15 365 women aged 35 to 65 years who were observed for incident
      diabetes from 1994 to 2005. Dietary intake of fiber and magnesium were measured
      with a validated food-frequency questionnaire. We estimated the relative risk
      (RR) by means of Cox proportional hazards analysis. We searched PubMed through
      May 2006 for prospective cohort studies of fiber and magnesium intake and risk of
      type 2 diabetes. We identified 9 cohort studies of fiber and 8 studies of
      magnesium intake and calculated summary RRs by means of a random-effects model.
      RESULTS: During 176 117 person-years of follow-up, we observed 844 incident cases
      of type 2 diabetes in the European Prospective Investigation Into Cancer and
      Nutrition-Potsdam. Higher cereal fiber intake was inversely associated with
      diabetes risk (RR for extreme quintiles, 0.72 [95% confidence interval [CI], 0.56
      0.93]), while fruit fiber (0.89 [95% CI, 0.70-1.13]) and vegetable fiber (0.93
      [95% CI, 0.74-1.17]) were not significantly associated. Meta-analyses showed a
      reduced diabetes risk with higher cereal fiber intake (RR for extreme categories,
      0.67 [95% CI, 0.62-0.72]), but no significant associations for fruit (0.96 [95%
      CI, 0.88-1.04]) and vegetable fiber (1.04 [95% CI, 0.94-1.15]). Magnesium intake
      was not related to diabetes risk in the European Prospective Investigation Into
      Cancer and Nutrition-Potsdam (RR for extreme quintiles, 0.99 [95% CI, 0.78
      1.26]); however, meta-analysis showed a significant inverse association (RR for
      extreme categories, 0.77 [95% CI, 0.72-0.84]). CONCLUSION: Higher cereal fiber
      and magnesium intakes may decrease diabetes risk.

PMID- 17502539
TI  - Physicians' understanding of the regulation of dietary supplements.
AB  - BACKGROUND: After passage of the Dietary Supplement Health and Education Act,
      herbs and other supplements were allowed to be sold to the public without Food
      and Drug Administration (FDA) approval or premarket evaluation. Data suggest that
      many people are unaware of this lack of governmental oversight and may rely on
      their physicians for education in this arena. This study was designed to evaluate
      physicians' level of understanding of dietary supplement regulation and the
      adverse event reporting process and to determine whether an interactive online
      curriculum could aid in improving knowledge. METHODS: A multicenter online
      educational intervention was developed and administered to physicians at 15
      internal medicine residency programs throughout the United States between March
      1, 2006, and June 30, 2006. Pretest performance was used to measure baseline
      knowledge, while posttest performance compared with pretest performance measured
      the effectiveness of the educational intervention. RESULTS: A total of 335
      physicians completed the module. Ninety percent of those completing the module
      were residents, while 10% were attending physicians. Baseline knowledge of
      dietary supplement regulatory issues was poor. The total average pretest score
      was only 59% (986/1675). The average score rose to 91% (1526/1675) after
      completion of the curriculum (P<.001). With regard to specific content areas,
      about one third of physicians were unaware that dietary supplements did not
      require FDA approval or submission of safety and efficacy data before being
      marketed. Similar percentages believed that there are regulations in place to
      ensure supplement quality. Most physicians were unaware that serious adverse
      events due to the use of supplements should be reported through the FDA MedWatch
      system. CONCLUSIONS: Physician knowledge of dietary supplement regulation and
      adverse event reporting is poor. An online didactic module may improve knowledge
      and potentially enhance patient-physician communication regarding the use of such
      products.

PMID- 17502540
TI  - Coronary artery disease in primary care.

PMID- 17502541
TI  - Does alcohol prevent mortality or does it just prevent coronary heart disease?

PMID- 17502542
TI  - Beware the burden of measurement.

PMID- 17502543
TI  - Withholding care in intracerebral hemorrhage: realistic compassion or self
      fulfilling prophecy?

PMID- 17502544
TI  - Axonal Charcot-Marie-Tooth disease: the fog is only slowly lifting.

PMID- 17502545
TI  - Early care limitations independently predict mortality after intracerebral
      hemorrhage.
AB  - OBJECTIVE: Intracerebral hemorrhage (ICH) is associated with a high early
      mortality rate. We examined the impact of early do not resuscitate (DNR) orders
      and other limitations in aggressive care on mortality after ICH in a community
      based study. METHODS: Cases of spontaneous ICH from 2000 to 2003 were identified
      from the Brain Attack Surveillance in Corpus Christi (BASIC) project, with deaths
      ascertained through 2005. Charts were reviewed for early (<24 hours from
      presentation) DNR orders, withdrawal of care, or deferral of other life
      sustaining interventions, analyzed together as combined DNR (C-DNR).
      Multivariable Cox-proportional hazards models were used to examine the
      association between short- and long-term all-cause mortality and early C-DNR,
      adjusted for demographics and established predictors of mortality after ICH.
      RESULTS: Of 18,393 subjects screened for cerebrovascular disease, 270 non
      traumatic ICH cases were included. Cumulative mortality risk was 0.43 at 30 days
      and 0.55 over the study course. Early C-DNR was noted in 34% of cases and was
      associated with a doubling in the hazard of death both at 30 days (hazard ratio
      [HR] 2.17, 95% CI 1.38, 3.41) and at end of follow-up (HR 1.92, 95% CI 1.29,
      2.87) despite adjustment for age, gender, ethnicity, Glasgow Coma Scale, ICH
      volume, intraventricular hemorrhage, and infratentorial hemorrhage. CONCLUSIONS:
      Early care limitations are independently associated with both short- and long
      term all-cause mortality after intracerebral hemorrhage (ICH) despite adjustment
      for expected predictors of ICH mortality. Physicians should carefully consider
      the effect of early limitations in aggressive care to avoid limiting care for
      patients who may survive their acute illness.

PMID- 17502546
TI  - Phenotype of Charcot-Marie-Tooth disease Type 2.
AB  - OBJECTIVE: To investigate the clinical and electrophysiologic phenotype of
      Charcot-Marie-Tooth disease (CMT) Type 2 in a large number of affected families.
      METHODS: We excluded CMT Type 1, hereditary neuropathy with liability to pressure
      palsies, and CMT due to Cx32 gene mutations by DNA analysis. We performed genetic
      analysis of the presently known CMT Type 2 genes. RESULTS: Sixty-one persons from
      18 families were affected. Ninety percent of patients were able to walk with or
      without the help of aids. Proximal leg muscle weakness was present in 13%.
      Asymmetrical features were present in 15%. Normal or brisk knee reflexes were
      present in 36%. Extensor plantar responses without associated spasticity occurred
      in 10 patients from eight families. Only three causative mutations were
      identified in the MFN2, BSCL2, and RAB7 genes. No mutations were found in the
      NEFL, HSPB1, HSPB8, GARS, DNM2, and GDAP1 genes. CONCLUSIONS: At group level, the
      clinical phenotype of Charcot-Marie-Tooth disease (CMT) Type 2 is uniform, with
      symmetric, distal weakness, atrophy and sensory disturbances, more pronounced in
      the legs than in the arms, notwithstanding the genetic heterogeneity. Brisk
      reflexes, extensor plantar responses, and asymmetrical muscle involvement can be
      considered part of the CMT Type 2 phenotype. The causative gene mutation was
      found in only 17% of the families we studied.

PMID- 17502548
TI  - CSF flow cytometry greatly improves diagnostic accuracy in CNS hematologic
      malignancies.
AB  - OBJECTIVE: To assess the diagnostic accuracy of flow cytometric immunophenotyping
      in comparison with classic cytomorphology for diagnosing CNS localizations of
      hematologic malignancies, and to evaluate the implications of CSF pleocytosis and
      protein content in this context. METHODS: We reviewed the results of diagnostic
      evaluations of all CSF samples analyzed for localization of a hematologic
      malignancy between 2001 and 2004 at our center. RESULTS: A total of 1,054 samples
      from 219 patients were available for analysis. Sixty patients had a CSF
      localization diagnosed by positive flow cytometry, cytomorphology, or both. The
      first sample was positive by flow cytometry in 44 (73%) patients, by
      cytomorphology in 19 (32%). Four first samples were positive by cytomorphology
      but negative by flow cytometry. Patients with positive cytomorphology had more
      frequent clinical symptomatology (95% vs 58%) and CSF pleocytosis (84% vs 25%),
      and tended to a poorer progression-free survival than patients with positive flow
      cytometry only. OR for CNS localization in case of CSF pleocytosis was 10.1 (95%
      CI 4.9 to 20.8); OR for CNS localization in case of elevated protein content was
      2.9 (95% CI 1.5 to 5.4). Nevertheless, 26 of 137 (19%) patients with normal cell
      count and protein concentration had a CNS localization. CONCLUSIONS: The
      diagnostic value of flow cytometry is more than twice that of cytomorphology.
      However, cytomorphologic examination of the CSF has additional diagnostic and
      possibly prognostic value, and should still be performed in conjunction with flow
      cytometry.

PMID- 17502547
TI  - CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis.
AB  - OBJECTIVE: To describe the relationship between symptomatology and time to
      diagnosis of an institutional series of patients with CNS germ cell tumor
      (CNSGCT) over a 16-year period. METHODS: Thirty consecutive patients newly
      diagnosed with CNSGCT (mean age 10.9 years; range 6 to 17 years; 70% boys) were
      evaluated at our institution between 1990 and 2006. RESULTS: Duration of symptoms
      prior to diagnosis ranged from 5 days to 3 years (mean 8.4 months). Tumor
      location included pineal (14), suprasellar (8), pineal/suprasellar (3),
      pineal/thalamic (4), and basal ganglionic/thalamic (3). Five patients had
      disseminated disease at the time of diagnosis. Features including headache,
      nausea, vomiting, and visual changes led to earlier diagnosis. Symptoms including
      movement disorders, enuresis, anorexia, and psychiatric complaints delayed
      diagnosis in 9 of 30 patients, diagnosed 7 months to 3 years (mean 22.3 months)
      from symptom onset. In 7 of 9 patients with delayed diagnosis, enuresis was
      present. Seventeen of 30 patients had signs of endocrine dysfunction at
      presentation that included diabetes insipidus (4), hypothyroidism (8), and growth
      hormone deficiency (4). Ophthalmologic findings of decreased visual acuity,
      visual field deficits, or ocular abnormalities were present in 13 patients.
      Duration of symptoms did not correlate with tumor subtype or event-free survival.
      In three patients with basal ganglionic/temporal lobe, thalamic, or
      pineal/suprasellar signal abnormalities on MRI, neuroradiographic diagnosis was
      difficult. CONCLUSIONS: Diagnosis of CNS germ cell tumor is often delayed, and
      presentation may include movement disorders or mimic psychiatric disease. MRI
      interpretation can be challenging and may require serum/CSF markers and biopsy
      for diagnosis.

PMID- 17502549
TI  - Modafinil for treatment of fatigue in post-polio syndrome: a randomized
      controlled trial.
AB  - OBJECTIVE: To determine if modafinil can improve fatigue in patients with post
      polio syndrome. METHODS: We used a randomized, placebo-controlled crossover
      trial. Intervention with modafinil (400 mg/day) and placebo occurred over 6-week
      periods. Primary endpoint (fatigue) was assessed using the Fatigue Severity Scale
      as the main outcome measure. Other measures included the Visual Analog Scale for
      Fatigue and the Fatigue Impact Scale. Secondary endpoint (health-related quality
      of life) was assessed using the 36-Item Short-Form. Analysis of variance for
      repeated measures was applied to assess treatment, period, and carryover effects.
      RESULTS: Thirty-six patients were randomized, 33 of whom (mean age: 61 years)
      completed required interventions. Treatment with modafinil was safe and well
      tolerated. After adjusting for periods and order effects, no difference was
      observed between treatments. CONCLUSION: Based on the utilized measures of
      outcome modafinil was not superior to placebo in alleviating fatigue or improving
      quality of life in the studied post-polio syndrome population.

PMID- 17502550
TI  - Is prestroke use of angiotensin-converting enzyme inhibitors associated with
      better outcome?
AB  - BACKGROUND: There is evidence that angiotensin-converting enzyme inhibitors
      (ACEIs) reduce the risk of stroke. However, it is unclear whether ACEI use before
      stroke provides a vasoprotective effect resulting in less severe stroke. METHODS:
      We ascertained all strokes occurring in a defined population in Melbourne,
      Australia. Prestroke use of ACEIs and concomitant medications was obtained from
      medical records. Initial neurologic deficit was dichotomized according to a NIH
      Stroke Scale (NIHSS) score < 8 (less severe deficit) or > or = 8 (severe
      deficit). Logistic regression was used to assess the association between
      prestroke use of ACEIs and stroke severity (measured by severity of neurologic
      deficits and death at 28 days). RESULTS: Seven hundred sixteen first-ever
      ischemic stroke patients were included. Previous use of ACEIs was independently
      associated with a reduced risk of severe neurologic deficits (odds ratio [OR]
      0.56; 95% CI 0.35 to 0.91) and death within 28 days (OR 0.46; 95% CI 0.24 to
      0.87). Diuretics were associated with an increased risk of severe neurologic
      deficits (OR 1.81; 95% CI 1.13 to 2.90). Factors associated with a greater NIHSS
      score were older age, atrial fibrillation, heart failure, and use of diuretics.
      These factors and claudication were associated with an increased risk of 28-day
      mortality, whereas use of anticoagulants was associated with a reduced risk of
      severe neurologic deficits and death. CONCLUSION: Within this large community
      based cohort, prestroke use of angiotensin-converting enzyme inhibitors was
      associated with a reduced risk of severe stroke.

PMID- 17502551
TI  - Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in
      Communities Study.
AB  - OBJECTIVE: This study examined the association between vascular headaches and
      retinal microvascular disease. METHODS: We investigated the cross-sectional
      association between headaches (migraine/other headaches with aura, migraine
      without aura, other headaches without aura, no headaches) and retinal
      microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous
      nicking; arteriolar and venular calibers) among middle-aged African American and
      white men and women from the third examination of the Atherosclerosis Risk in
      Communities Study (1993 through 1995). RESULTS: After controlling for age,
      gender, race, study center, and cardiovascular risk factors, we determined that
      persons with headaches were more likely to have retinopathy than those without a
      history of headaches (odds ratio [OR] = 1.38, 95% CI = 0.96 to 1.99 for
      migraine/other headaches with aura; OR = 1.49, 95% CI = 1.05 to 2.12 for migraine
      without aura; and OR = 1.28, 95% CI = 0.99 to 1.65 for other headaches).
      Associations with migraine were stronger among the subset of participants without
      a history of diabetes or hypertension (OR = 1.79, 95% CI = 1.09 to 2.95 for
      migraine/other headaches with aura; and OR = 1.74, 95% CI = 1.11 to 2.71 for
      migraine without aura). Headaches were not associated with focal arteriolar
      narrowing or arteriovenous nicking. Persons with headaches tended to have smaller
      mean arteriolar and venular calibers; however, these associations did not tend to
      persist among those without hypertension or diabetes. CONCLUSION: Middle-aged
      persons with migraine and other headaches were more likely to have retinopathy
      signs, supporting the hypothesis that neurovascular dysfunction may underlie
      vascular headaches.

PMID- 17502552
TI  - Comparison and predictors of rash associated with 15 antiepileptic drugs.
AB  - OBJECTIVE: To determine predictors and relative incidence of antiepileptic drug
      (AED)-related rash in patients taking all common AEDs. METHODS: We reviewed 1,890
      outpatients. Eighty-one variables were tested as potential predictors of rash. We
      compared the rate of rash attributed to each AED (AED rash) with the average rate
      of rash attributed to the other AEDs in all adults (aged > or =16 years; n =
      1,649) when taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM),
      gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC),
      phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate
      (TPM), vigabatrin (VGB), valproate (VPA), or zonisamide (ZNS). We repeated this
      analysis for patients with and without the identified nondrug predictors of AED
      rash. RESULTS: The average rate of AED rash was 2.8%. The only nondrug predictor
      significant in multivariate analysis was occurrence of another AED rash (odds
      ratio 3.1, 95% CI 1.8 to 5.1; p < 0.0001); the rate of rash in this subgroup was
      8.8%, vs 1.7% in those without another AED rash. Higher AED rash rates were seen
      with PHT (5.9% overall, p = 0.0008; 25.0% in those with another AED rash, p =
      0.001), LTG (4.8%, p = 0.00095; 14.4%, p = 0.025), and CBZ (3.7%, not
      significant; 16.5%, p = 0.01). Lower rates were seen with LEV (0.6% overall; p =
      0.00042), GBP (0.3%, p = 0.00035), and VPA (0.7%, p = 0.01). Rash rates were also
      low (<1% overall) with FBM, PRM, TPM, and VGB (not significant). These AED
      differences remained similar in patients with and without other AED rashes. There
      were four cases of Stevens-Johnson syndrome involving four AEDs. CONCLUSIONS: The
      rate of an antiepileptic drug (AED) rash is approximately five times greater in
      patients with another AED rash (8.8%) vs those without (1.7%). Rash rates were
      highest with phenytoin, lamotrigine, and carbamazepine and low (<1%) with several
      AEDs.

PMID- 17502553
TI  - Predictors of diagnosis in Huntington disease.
AB  - OBJECTIVE: Subtle signs and symptoms of Huntington disease (HD) are often present
      before impairments reach a point where the neurologic disease is manifest and a
      diagnosis must be considered. The objective is to examine the prognostic
      significance of these early clinical signs and symptoms regarding time until
      unequivocal clinical HD diagnosis. METHODS: We analyzed longitudinal data from
      218 at-risk but healthy participants in the Huntington Study Group database who
      had either normal motor examination results or minimal soft motor signs at first
      observation. This group was followed periodically in HD clinics for up to 4.5
      years. We used survival analysis to examine predictors of time until HD
      diagnosis. RESULTS: Diagnostic prediction was significantly improved using
      specific, nonredundant items from the Unified Huntington's Disease Rating Scale.
      When a movement disorder specialist initially had a global impression of "soft
      signs" present, cumulative relative risk of diagnosis was 4.68 times greater at
      1.5 years of follow-up and 3.58 at 3 years. A neuropsychological test pattern
      with psychomotor speed 1 SD worse than a semantic knowledge measure increased
      cumulative risk by 1.99 times at 1.5 years and 1.81 at 3 years. Finally, reports
      of various subjective HD symptoms increased 3-year relative risk by 2.6 to 3.4.
      CONCLUSIONS: Findings demonstrate that neuropsychological performance and both
      the clinician rating and the patient subjective perception of motor difficulties
      contribute nonredundantly to a prediction of Huntington disease diagnosis. These
      findings may have implications for prognostic assessment of persons at risk and
      eventually assist with early interventions.

PMID- 17502554
TI  - Imaging beta-amyloid burden in aging and dementia.
AB  - OBJECTIVE: To compare brain beta-amyloid (Abeta) burden measured with
      [(11)C]Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD),
      and other dementias. METHODS: Thirty-three subjects with dementia (17 AD, 10
      dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects
      with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects
      (HCs) were studied. Abeta burden was quantified using PIB distribution volume
      ratio. RESULTS: Cortical PIB binding was markedly elevated in every AD subject
      regardless of disease severity, generally lower and more variable in DLB, and
      absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or
      normal pattern. Binding was greatest in the precuneus/posterior cingulate,
      frontal cortex, and caudate nuclei, followed by lateral temporal and parietal
      cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological
      scores. PIB binding did not correlate with dementia severity in AD or DLB but was
      higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated
      inversely with the interval from onset of cognitive impairment to diagnosis.
      CONCLUSIONS: Pittsburgh Compound B PET findings match histopathologic reports of
      beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal
      studies to better understand the role of amyloid deposition in the course of
      neurodegeneration and to determine if Abeta deposition in nondemented subjects is
      preclinical AD are now feasible. Our findings also suggest that Abeta may
      influence the development of dementia with Lewy bodies, and therefore strategies
      to reduce Abeta may benefit this condition.

PMID- 17502555
TI  - Cholinesterase inhibitors reduce cortical Abeta in dementia with Lewy bodies.
AB  - Cholinesterase inhibitors (ChEIs) are effective symptomatic treatments in
      dementia with Lewy bodies (DLB), although effects on pathologic mechanisms are
      unknown. In the first human autopsy study examining the impact of ChEI treatment
      on brain pathology, we compared treated patients with DLB with matched untreated
      patients for cortical beta-amyloid (Abeta) and tau pathologies. Treated patients
      with DLB had significantly less parenchymal Abeta deposition, which is relevant
      to disease management and treatment of dementia patients using ChEI.

PMID- 17502556
TI  - Neurovascular unit dysfunction: a vascular component of Alzheimer disease?

PMID- 17502557
TI  - The Americans with Disabilities Act: disabled by court decisions.

PMID- 17502558
TI  - On the experience of epilepsy.

PMID- 17502559
TI  - Speech automatisms in a second language in complex partial seizures: a video-EEG
      study.

PMID- 17502560
TI  - MELAS associated with mutations in the POLG1 gene.

PMID- 17502561
TI  - Tuberculous meningovasculitis.

PMID- 17502562
TI  - CNS blastomycosis in a young man working in fields after Hurricane Katrina.

PMID- 17502563
TI  - Effect of a clinical stroke on the risk of dementia in a prospective cohort.

PMID- 17502564
TI  - The case of the reed in the breeze.

PMID- 17502565
TI  - Effects of rivastigmine on cognitive function in patients with traumatic brain
      injury.

PMID- 17502566
TI  - Myocardial injury in patients with intracerebral hemorrhage treated with
      recombinant factor VIIa.

PMID- 17502567
TI  - Radiofrequency catheter ablation of chronic atrial fibrillation guided by complex
      electrograms.
AB  - BACKGROUND: Radiofrequency catheter ablation of atrial fibrillation (AF) guided
      by complex fractionated atrial electrograms has been reported to eliminate AF in
      a large proportion of patients. However, only a small number of patients with
      chronic AF have been included in previous studies. METHODS AND RESULTS: In 100
      patients (mean age, 57+/-11 years) with chronic AF, radiofrequency ablation was
      performed to target complex fractionated atrial electrograms at the pulmonary
      vein ostial and antral areas, various regions of the left atrium, and the
      coronary sinus until AF terminated or all identified complex fractionated atrial
      electrograms were eliminated. Ablation sites consisted of > or = 1 pulmonary vein
      in 46% of patients; the left atrial septum, roof, or anterior wall in all; and
      the coronary sinus in 55%. During 14+/-7 months of follow-up after a single
      ablation procedure, 33% of patients were in sinus rhythm without antiarrhythmic
      drugs, 38% had AF, 17% had both AF and atrial flutter, 9% had persistent atrial
      flutter, and 3% had paroxysmal AF on antiarrhythmic drugs. A second ablation
      procedure was performed in 44% of patients. Pulmonary vein tachycardia was found
      in all patients in both previously targeted and nontargeted pulmonary veins.
      There were multiple macroreentrant circuits in the majority of patients with
      atrial flutter. At 13+/-7 months after the last ablation procedure, 57% of
      patients were in sinus rhythm without antiarrhythmic drugs, 32% had persistent
      AF, 6% had paroxysmal AF, and 5% had atrial flutter. CONCLUSIONS: Modest short
      term efficacy is achievable with radiofrequency ablation of chronic AF guided by
      complex fractionated atrial electrograms, but only after a second ablation
      procedure in > 40% of patients. Rapid activity in the pulmonary veins and
      multiple macroreentrant circuits are common mechanisms of recurrent atrial
      arrhythmias.

PMID- 17502568
TI  - Sustained benefit at 2 years of primary femoropopliteal stenting compared with
      balloon angioplasty with optional stenting.
AB  - BACKGROUND: Primary stenting with self-expanding nitinol stents of the
      superficial femoral artery yielded improved morphological and clinical results
      compared with balloon angioplasty with optional stenting until 12 months in a
      randomized controlled trial. We now report 2-year data on restenosis and clinical
      outcomes of these patients. METHODS AND RESULTS: Of 104 patients with chronic
      limb ischemia and superficial femoral artery obstructions, 98 (94%) could be
      followed up until 2 years after intervention for occurrence of restenosis (>50%)
      by duplex ultrasound and for clinical and hemodynamic outcome by treadmill
      walking distance and ankle brachial index. Restenosis rates at 2 years were 45.7%
      (21 of 46) versus 69.2% (36 of 52) in favor of primary stenting compared with
      balloon angioplasty with optional secondary stenting by an intention-to-treat
      analysis (P=0.031). Consistently, stenting (whether primary or secondary; n=63)
      was superior to plain balloon angioplasty (n=35) with respect to the occurrence
      of restenosis (49.2% versus 74.3%; P=0.028) by a treatment-received analysis.
      Clinically, patients in the primary stent group showed a trend toward better
      treadmill walking capacity (average, 302 versus 196 m; P=0.12) and better ankle
      brachial index values (average, 0.88 versus 0.78; P=0.09) at 2 years,
      respectively. Reintervention rates tended to be lower after primary stenting (17
      of 46 [37.0%] versus 28 of 52 [53.8%]; P=0.14). CONCLUSIONS: At 2 years, primary
      stenting with self-expanding nitinol stents for the treatment of superficial
      femoral artery obstructions yields a sustained morphological benefit and a trend
      toward clinical benefit compared with balloon angioplasty with optional stenting.

PMID- 17502569
TI  - Treatment of hypertension in the prevention and management of ischemic heart
      disease: a scientific statement from the American Heart Association Council for
      High Blood Pressure Research and the Councils on Clinical Cardiology and
      Epidemiology and Prevention.

PMID- 17502570
TI  - View-synchronized robotic image-guided therapy for atrial fibrillation ablation:
      experimental validation and clinical feasibility.
AB  - BACKGROUND: A robotic catheter navigation system has been developed that provides
      a significant degree of freedom of catheter movement. This study examines the
      feasibility of synchronizing this robotic navigation system with electroanatomic
      mapping and 3-dimensional computed tomography imaging to perform view
      synchronized left atrial (LA) ablation. METHODS AND RESULTS: This study consisted
      of a porcine experimental validation phase (9 animals) and a clinical feasibility
      phase (9 atrial fibrillation patients). Preprocedural computed tomography images
      were reconstructed to provide 3-dimensional surface models of the LA pulmonary
      veins and aorta. Aortic electroanatomic mapping was performed manually, followed
      by registration with the corresponding computed tomography aorta image using
      custom software. The mapping catheter was remotely manipulated with the robotic
      navigation system within the registered computed tomography image of the LA
      pulmonary veins. The point-to-surface error between the LA electroanatomic
      mapping data and the computed tomography image was 2.1+/-0.7 and 1.6+/-0.1 mm in
      the preclinical and clinical studies, respectively. The catheter was remotely
      navigated into all pulmonary veins, the LA appendage, and circumferentially along
      the mitral valve annulus. In 7 of 9 animals, circumferential radiofrequency
      ablation lesions were applied periostially to ablate 11 pulmonary veins. In
      patients, all of the pulmonary veins were remotely electrically isolated in an
      extraostial fashion. Adjunctive ablation included superior vena cava isolation in
      6 patients, cavotricuspid isthmus ablation in 5 patients, and ablation of sites
      of complex fractionated activity and atypical LA flutters in 3 patients.
      CONCLUSIONS: This study demonstrates the safety and feasibility of an emerging
      paradigm for atrial fibrillation ablation involving the confluence of 3
      technologies: 3-dimensional imaging, electroanatomic mapping, and remote robotic
      navigation.

PMID- 17502571
TI  - Risk factors for the progression of coronary artery calcification in asymptomatic
      subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: The Multi-Ethnic Study of Atherosclerosis (MESA) provides an
      opportunity to study the association of traditional cardiovascular risk factors
      with the incidence and progression of coronary artery calcium (CAC) in a large
      community-based cohort with no evidence of clinical cardiovascular disease.
      METHODS AND RESULTS: Follow-up CAC measurements were available for 5756
      participants with an average of 2.4 years between scans. The incidence of newly
      detectable CAC averaged 6.6% per year. Incidence increased steadily across age,
      ranging from <5% annually in those <50 years of age to >12% in those >80 years of
      age. Median annual change in CAC for those with existing calcification at
      baseline was 14 Agatston units for women and 21 Agatston units for men. Most
      traditional cardiovascular risk factors were associated with both the risk of
      developing new incident coronary calcium and increases in existing calcification.
      These included age, male gender, white race/ethnicity, hypertension, body mass
      index, diabetes mellitus, glucose, and family history of heart attack. Factors
      also existed that were related only to incident CAC risk, such as low- and high
      density lipoprotein cholesterol and creatinine. Diabetes mellitus had the
      strongest association with CAC progression for blacks and the weakest for
      Hispanics, with intermediate associations for whites and Chinese. CONCLUSIONS:
      This is the first large multiethnic study reporting on the incidence and
      progression of CAC. Standard coronary risk factors were generally related to both
      CAC incidence and progression. Whites had more incident CAC and CAC progression
      than the other 3 racial/ethnic groups. Except for diabetes mellitus, risk factor
      relationships were similar across racial/ethnic groups.

PMID- 17502572
TI  - Local production of lipoprotein-associated phospholipase A2 and
      lysophosphatidylcholine in the coronary circulation: association with early
      coronary atherosclerosis and endothelial dysfunction in humans.
AB  - BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel marker
      and participant in vascular inflammation. Inflammation also is associated with
      coronary atherosclerosis. We tested the hypothesis that local coronary production
      of Lp-PLA2 is enhanced in patients with early coronary atherosclerosis and
      associated with local endothelial function. METHODS AND RESULTS: Coronary
      angiography, blood flow, flow reserve, endothelial function assessment, and
      intravascular ultrasound with volumetric analysis were performed in 15 patients
      with mild coronary atherosclerosis and in 15 control subjects. Plasma samples
      were collected simultaneously from the left main coronary artery and coronary
      sinus for measurement of Lp-PLA2, lysophosphatidylcholine (a product of Lp-PLA2),
      and C-reactive protein. Hemodynamic parameters and cholesterol were similar in
      both groups. Arterial Lp-PLA2 levels were similar in patients and control
      subjects: 225 ng/mL (interquartile range [IQR], 196 to 273 ng/mL) versus 221
      ng/mL (IQR, 177 to 294 ng/mL). Lp-PLA2 net production in the coronary circulation
      was higher in patients compared with control subjects: 519 ng/min (IQR, 198 to
      1276 ng/min) versus -529 ng/min (IQR, -872 to -79 ng/min; P=0.001) and correlated
      with percent atheroma volume (r(s)=0.37, P=0.04). Net production of
      lysophosphatidylcholine was higher in patients compared with control subjects:
      199 ng/min (IQR, -592 to 470 ng/min) versus -505 ng/min (IQR, -1119 to 0 ng/min;
      P=0.03) and correlated with coronary endothelial dysfunction (r(s)=0.5, P=0.005).
      C-reactive protein was not significantly different between the groups.
      CONCLUSIONS: Early coronary atherosclerosis in humans is characterized by local
      production of Lp-PLA2. Local coronary production of lysophosphatidylcholine, the
      active product of Lp-PLA2, is associated with endothelial dysfunction. These
      results support the role for Lp-PLA2 in the mechanism of regional vascular
      inflammation and atherosclerosis in humans.

PMID- 17502573
TI  - Catheter ablation of multiple ventricular tachycardias after myocardial
      infarction guided by combined contact and noncontact mapping.
AB  - BACKGROUND: Insights gained from noncontact mapping of ventricular tachycardia
      (VT) have not been systematically applied to contact maps. This study sought to
      unify both techniques for an individualized approach to the patient with multiple
      ischemic VTs irrespective of cycle length. METHODS AND RESULTS: For 12
      consecutive patients with chronic myocardial infarction and recurrent VT, bipolar
      contact maps were acquired during sinus or paced rhythm. Additional noncontact
      maps were obtained during 48 induced VTs (cycle length 192 to 579 ms).
      Endocardial exit sites were superimposed on contact maps and verified by pace
      mapping. Radiofrequency lesions were extended for critical borders defined by
      multiple neighboring exits and followed the isovoltage contour line of contact
      maps. Nine critical borders were identified in 8 patients and constituted the
      substrate for 31 VTs. The voltage at exit sites was 0.8 mV (range 0.1 to 2.3).
      Noncontact maps revealed 23+/-18% of isthmus conduction. Thirty-seven (77%) of
      all and 83% of clinically documented VTs were rendered noninducible irrespective
      of cycle length by application of 27 radiofrequency lesions (range 18 to 56).
      Spontaneous transitions between distinct VTs along critical borders were
      demonstrated in 4 patients. Pace-mapping reproduced the QRS morphology of 81% of
      VTs and was associated with successful ablation (P<0.01). Noninducibility of any
      sustained VT was reached for 8 (67%) patients. During 15 months (range 5 to 28)
      of follow-up, 8 patients remained without recurrence, and VT episodes were
      reduced in the other 4 patients (P<0.01). VT cycle length was not predictive for
      acute or long-term success. CONCLUSIONS: The combined approach of contact and
      noncontact mapping effectively defines critical borders as the substrate of
      multiple VTs without limitation for unstable VTs.

PMID- 17502574
TI  - Indicators of poor prognosis of acute pericarditis.
AB  - BACKGROUND: The clinical search for indicators of poor prognosis of acute
      pericarditis may be useful for clinical triage of patients at high risk of
      specific causal conditions or complications. The aim of the present article is to
      assess the relationship between clinical features at presentation and specific
      causes or complications. METHODS AND RESULTS: A total of 453 patients aged 17 to
      90 years (mean age 52+/-18 years, 245 men) with acute pericarditis (post
      myocardial infarction pericarditis was excluded) were prospectively evaluated
      from January 1996 to August 2004. A specific cause was found in 76 of 453
      patients (16.8%): autoimmune in 33 patients (7.3%), neoplastic in 23 patients
      (5.1%), tuberculous in 17 patients (3.8%), and purulent in 3 patients (0.7%). In
      multivariable analysis, women (hazard ratio [HR] 1.67, 95% confidence interval
      [CI] 1.03 to 2.70; P=0.036) and patients with fever >38 degrees C (HR 3.56, 95%
      CI 1.82 to 6.95; P<0.001), subacute course (HR 3.97, 95% CI 1.66 to 9.50;
      P=0.002), large effusion or tamponade (HR 2.15, 95% CI 1.09 to 4.23; P=0.026),
      and failure of aspirin or of nonsteroidal anti-inflammatory drugs (HR 2.50, 95%
      CI 1.28 to 4.91; P=0.008) were at increased risk of specific causal conditions.
      After a mean follow-up of 31 months, complications were detected in 95 patients
      (21.0%): recurrences in 83 patients (18.3%), tamponade in 14 patients (3.1%), and
      constriction in 7 patients (1.5%). In multivariable analysis, women (HR 1.65, 95%
      CI 1.08 to 2.52; P=0.020) and patients with large effusion or tamponade (HR 2.51,
      95% CI 1.37 to 4.61; P=0.003) and failure of aspirin or of nonsteroidal anti
      inflammatory drugs (HR 5.50, 95% CI 3.56 to 8.51; P<0.001) were at increased risk
      of complications. CONCLUSIONS: Specific clinical features (fever >38 degrees C,
      subacute course, large effusion or tamponade, and aspirin or NSAID failure) may
      be useful to identify higher risk of specific causal conditions and
      complications.

PMID- 17502575
TI  - Diagnostic miscues in congenital long-QT syndrome.
AB  - BACKGROUND: Long-QT syndrome (LQTS) is a potentially lethal cardiac channelopathy
      that can be mistaken for palpitations, neurocardiogenic syncope, and epilepsy.
      Because of increased physician and public awareness of warning signs suggestive
      of LQTS, there is the potential for LQTS to be overdiagnosed. We sought to
      determine the agreement between the dismissal diagnosis from an LQTS subspecialty
      clinic and the original referral diagnosis. METHODS AND RESULTS: Data from the
      medical record were compared with data from the outside evaluation for 176
      consecutive patients (121 females, median age 16 years, average referral
      corrected QT interval [QTc] of 481 ms) referred with a diagnosis of LQTS. After
      evaluation at Mayo Clinic's LQTS Clinic, patients were categorized as having
      definite LQTS (D-LQTS), possible LQTS (P-LQTS), or no LQTS (No-LQTS). Seventy
      three patients (41%) were categorized as No-LQTS, 56 (32%) as P-LQTS, and only 47
      (27%) as D-LQTS. The yield of genetic testing among D-LQTS patients was 78%
      compared with 34% for P-LQTS and 0% among No-LQTS patients (P<0.0001). The
      average QTc was greater in either D-LQTS or P-LQTS than in No-LQTS (461 versus
      424 ms, P<0.0001). Vasovagal syncope was more common among the No-LQTS subset
      (28%) than the P-LQTS/D-LQTS group (8%; P=0.04). Determinants for discordance
      (ie, positive outside diagnosis versus No-LQTS) included overestimation of QTc,
      diagnosing LQTS on the basis of "borderline" QTc values, and interpretation of a
      vasovagal fainting episode as an LQTS-precipitated cardiac event. CONCLUSIONS:
      Diagnostic concordance was present for less than one third of the patients who
      sought a second opinion. Two of every 5 patients referred with the diagnosis of
      LQTS departed without such a diagnosis. Miscalculation of the QTc,
      misinterpretation of the normal distribution of QTc values, and misinterpretation
      of symptoms appear to be responsible for most of the diagnostic miscues.

PMID- 17502576
TI  - Biglycan deficiency causes spontaneous aortic dissection and rupture in mice.
AB  - BACKGROUND: For the majority of cases, the cause of spontaneous aortic dissection
      and rupture is unknown. An inherited risk is associated with Marfan syndrome,
      Ehlers-Danlos syndrome type IV, and loci mapped to diverse autosomal chromosomes.
      Analysis of pedigrees however has indicated that it may be also inherited as an X
      linked trait. The biglycan gene, found on chromosome X in humans and mice,
      encodes a small leucine-rich proteoglycan involved in the integrity of the
      extracellular matrix. A vascular phenotype has never been described in mice
      deficient in the gene for small leucine-rich proteoglycans. In the breeding of
      BALB/cA mice homozygous for a null mutation of the biglycan gene, we observed
      that 50% of biglycan-deficient male mice died suddenly within the first 3 months
      of life. METHODS AND RESULTS: Necropsies revealed a major hemorrhage in the
      thoracic or abdominal cavity, and histology showed aortic rupture that involved
      an intimal and medial tear as well as dissection between the media and
      adventitia. By transmission electron microscopy and biomechanical testing, the
      aortas of biglycan-deficient mice showed structural abnormalities of collagen
      fibrils and reduced tensile strength. Similar collagen fibril changes were
      observed in male as well as in female biglycan-deficient mice, which implies a
      role of additional determinants such as gender-related response to stress in the
      development of this vascular catastrophe only in male mice. CONCLUSIONS: The
      spontaneous death of biglycan-deficient male mice from aortic rupture implicates
      biglycan as essential for the structural and functional integrity of the aortic
      wall and suggests a potential role of biglycan gene defects in the pathogenesis
      of aortic dissection and rupture in humans.

PMID- 17502577
TI  - Randomized, double-blind, dose-ranging study of otamixaban, a novel, parenteral,
      short-acting direct factor Xa inhibitor, in percutaneous coronary intervention:
      the SEPIA-PCI trial.
AB  - BACKGROUND: The optimal anticoagulant regimen for percutaneous coronary
      intervention (PCI) remains to be determined. Otamixaban, a selective and direct
      inhibitor of factor Xa, was investigated in patients undergoing nonurgent
      percutaneous coronary intervention. METHODS AND RESULTS: In this double-blind,
      double-dummy, parallel-group, dose-ranging trial, 947 patients were randomly
      assigned to either 1 of 5 weight-adjusted otamixaban regimens or weight-adjusted
      unfractionated heparin (UFH) before percutaneous coronary intervention. The
      primary end points were change in prothrombin fragments 1+2 (F1+2), and anti
      factor Xa activity. The main secondary end points were Thrombolysis In Myocardial
      Infarction (TIMI) bleeding at day 3 or hospital discharge (whichever came first)
      and 30-day ischemic events. The median change in F1+2 from baseline to the end of
      infusion was greater with the highest otamixaban dose compared with UFH (-0.3
      versus -0.2 ng/mL, P=0.008). Anti-factor Xa levels were 65, 155, 393, 571, and
      691 ng/mL with otamixaban doses 1 to 5, respectively. Significant TIMI bleeding
      (major or minor) occurred in 2.0%, 1.9%, 3.8%, 3.9%, and 2.6% of patients
      receiving otamixaban doses 1 to 5, respectively, and in 3.8% of patients
      receiving UFH. Four TIMI major bleeds were observed. Ischemic events occurred in
      5.8%, 7.1%, 3.8%, 2.5%, and 5.1% of patients receiving otamixaban doses 1 to 5,
      respectively, and in 5.6% of patients receiving UFH. CONCLUSIONS: Otamixaban
      reduced F1+2 significantly more than UFH at the highest dose regimen, whereas no
      significant difference in the incidence of TIMI bleeding was observed between the
      otamixaban and UFH groups. These results set the stage for adequately powered
      clinical outcome trials of selective direct factor Xa inhibition in patients with
      acute coronary syndromes.

PMID- 17502578
TI  - Accuracy of serial National Institutes of Health Stroke Scale scores to identify
      artery status in acute ischemic stroke.
AB  - BACKGROUND: Early recovery after intravenous thrombolysis can be observed in
      stroke; however, the utility of measuring clinical improvement to assess artery
      status has not been established. We sought to determine the accuracy of serial
      National Institutes of Health Stroke Scale (NIHSS) scores to detect complete
      early recanalization of the middle cerebral artery. METHODS AND RESULTS: Data
      from the CLOTBUST trial (Combined Lysis of Thrombus in Brain Ischemia Using
      Transcranial Ultrasound and Systemic tPA) were used to determine the most
      sensitive and specific NIHSS-derived parameter to identify complete
      recanalization. Then, reproducibility was tested against a separate patient
      population (Barcelona data set). NIHSS scores were determined before tissue
      plasminogen activator bolus and at 60 and 120 minutes in both data sets. Receiver
      operating characteristic curves were used to compare test performance. The
      accuracy of individual cutoffs was demonstrated by sensitivity, specificity, and
      positive and negative predictive values. A total of 122 patients in the CLOTBUST
      data set and 98 in the Barcelona data set received 0.9 mg/kg intravenous tissue
      plasminogen activator [mean age 69+/-12 versus 72+/-12 years, 57% male versus 51%
      male, median NIHSS 16 versus 17 points, mean time from onset to treatment 140+/
      32 versus 177+/-59 minutes, and complete recanalization of the middle cerebral
      artery in 19% versus 17%). For identification of recanalization, an NIHSS score
      reduction of > or = 40% offered the best tradeoff, with sensitivity, specificity,
      positive predictive value, and negative predictive value of 65%, 85%, 50%, and
      91% at 60 minutes and 74%, 80%, 58%, and 89% at 120 minutes, respectively. Test
      performance was equal in the Barcelona data set. CONCLUSIONS: Relative changes in
      serial NIHSS scores can serve as a simple clinical indicator of arterial status
      after intravenous thrombolysis. Accuracy parameters are affected by the process
      of recanalization and its varying clinical significance.

PMID- 17502579
TI  - Images in cardiovascular medicine. The use of 2 contrast filling patterns in the
      diagnosis of a giant coronary aneurysm.

PMID- 17502580
TI  - Images in cardiovascular medicine. "Elephant trunk" mimicking thoracic aortic
      dissection: the role of intravascular ultrasound.

PMID- 17502581
TI  - Images in cardiovascular medicine. Intramural dissecting hemorrhage of the
      myocardium.

PMID- 17502582
TI  - Letter by McLachlan et al regarding article, "Cough cardiopulmonary resuscitation
      revisited".

PMID- 17502583
TI  - Letter by Harder et al regarding article, "Low birth weight, a risk factor for
      cardiovascular diseases in later life, is already associated with elevated fetal
      glycosylated hemoglobin at birth".

PMID- 17502584
TI  - Pioneers in cardiology: Professor Pim de Feyter, MD, PhD. Interview by Monika
      Polak.

PMID- 17502585
TI  - Transvenous implantable cardioverter-defibrillator leads: the weakest link.

PMID- 17502586
TI  - Fetuin-A, valve calcification, and diabetes: what do we understand?

PMID- 17502587
TI  - Heritability, platelet function, and aspirin: a link established but cause
      unknown.

PMID- 17502588
TI  - Mast cells as mediators and modulators of atherogenesis.

PMID- 17502589
TI  - Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory
      cascade in cardiac physiology and disease.

PMID- 17502590
TI  - Acute coronary care in the elderly, part I: Non-ST-segment-elevation acute
      coronary syndromes: a scientific statement for healthcare professionals from the
      American Heart Association Council on Clinical Cardiology: in collaboration with
      the Society of Geriatric Cardiology.
AB  - BACKGROUND: Age is an important determinant of outcomes for patients with acute
      coronary syndromes (ACS); however, community practice reveals a
      disproportionately lower use of cardiovascular medications and invasive treatment
      even among elderly patients with ACS who would stand to benefit. Reasons include
      limited trial data to guide the care of older adults and uncertainty about
      benefits and risks, particularly with newer medications or invasive treatments
      and in the setting of advanced age or complex health status. METHODS AND RESULTS:
      This 2-part American Heart Association scientific statement summarizes evidence
      on patient heterogeneity, clinical presentation, and treatment of non-ST
      elevation ACS in relation to age (< 65, 65 to 74, 75 to 84, and > or = 85 years).
      In addition, we review methodological issues that influence the acquisition and
      application of evidence to the elderly patients treated in community practice. A
      writing group combining international cardiovascular and geriatric perspectives
      convened to summarize available data from trials (5 combined Virtual Coordinating
      Center for Global Collaborative Cardiovascular Research [VIGOUR] trials) and 3
      registries (Global Registry of Acute Coronary Events, National Registry of
      Myocardial Infarction, and the Can Rapid risk stratification of Unstable angina
      patients Suppress ADverse outcomes with Early implementation of the American
      College of Cardiology/American Heart Association guidelines national quality
      improvement initiative [CRUSADE]) to provide a conceptual framework for future
      work in the care of the elderly with acute cardiac disease. Treatment for non-ST
      segment-elevation ACS (Part I) and ST-segment-elevation myocardial infarction
      (Part II) are reviewed. In addition, ethical considerations pertaining to acute
      care and secondary prevention are considered (Part II). The primary goal is to
      identify the areas in which sufficient evidence is available to guide practice,
      as well as to determine areas that warrant further study. Although treatment
      related benefits should rise in an elderly population with high disease risk,
      data to assess these benefits are limited, outcomes of importance vary, and
      heterogeneity among the elderly increases treatment-related risks. Although a
      uniform approach to care in the oldest of the old is unlikely, understanding the
      major contributors to benefits and risks from treatment will advance the ability
      to apply guideline-based care in this subset of patients. CONCLUSIONS: Although a
      few recent trials have described treatment effects in older patients, others
      continue to exclude patients on the basis of age. Going forward, prospective
      trials should enroll elderly subjects proportionate to their prevalence among the
      treated population to define risk and benefit. Findings from age subgroup
      analyses should be reported in a consistent manner across trials, including
      absolute and relative risks for efficacy and safety. Outcomes of particular
      relevance to the elderly, such as quality of life, physical function, and
      independence, should also be considered. Creatinine clearance should be
      calculated for every elderly patient to enable appropriate dosing. In addition,
      physicians need an understanding of conditions unique to older patients (eg,
      frailty, cognitive impairment) that influence treatment goals and outcomes. With
      these efforts, treatment risks can be minimized, and benefits can be placed in
      the health context of the elderly patient with ACS.

PMID- 17502591
TI  - Acute coronary care in the elderly, part II: ST-segment-elevation myocardial
      infarction: a scientific statement for healthcare professionals from the American
      Heart Association Council on Clinical Cardiology: in collaboration with the
      Society of Geriatric Cardiology.
AB  - BACKGROUND: Age is an important determinant of outcomes for patients with acute
      coronary syndromes. However, community practice reveals a disproportionately
      lower use of cardiovascular medications and invasive treatment even among elderly
      patients who would stand to benefit. Limited trial data are available to guide
      care of older adults, which results in uncertainty about benefits and risks,
      particularly with newer medications or invasive treatments and in the setting of
      advanced age and complex health status. METHODS AND RESULTS: Part II of this
      American Heart Association scientific statement summarizes evidence on
      presentation and treatment of ST-segment-elevation myocardial infarction in
      relation to age (< 65, 65 to 74, 75 to 84, and > or = 85 years). The purpose of
      this statement is to identify areas in which the evidence is sufficient to guide
      practice in the elderly and to highlight areas that warrant further study.
      Treatment-related benefits should rise in an elderly population, yet data to
      confirm these benefits are limited, and the heterogeneity of older populations
      increases treatment-associated risks. Elderly patients with ST-segment-elevation
      myocardial infarction more often have relative and absolute contraindications to
      reperfusion, so eligibility for reperfusion declines with age, and yet elderly
      patients are less likely to receive reperfusion even if eligible. Data support a
      benefit from reperfusion in elderly subgroups up to age 85 years. The selection
      of reperfusion strategy is determined more by availability, time from
      presentation, shock, and comorbidity than by age. Additional data are needed on
      selection and dosing of adjunctive therapies and on complications in the elderly.
      A "one-size-fits-all" approach to care in the oldest old is not feasible, and
      ethical issues will remain even in the presence of adequate evidence.
      Nevertheless, if the contributors to treatment benefits and risks are understood,
      guideline-recommended care may be applied in a patient-centered manner in the
      oldest subset of patients. CONCLUSIONS: Few trials have adequately described
      treatment effects in older patients with ST-segment-elevation myocardial
      infarction. In the future, absolute and relative risks for efficacy and safety in
      age subgroups should be reported, and trials should make efforts to enroll the
      elderly in proportion to their prevalence among the treated population. Outcomes
      of particular relevance to the older adult, such as quality of life, physical
      function, and independence, should also be evaluated, and geriatric conditions
      unique to this age group, such as frailty and cognitive impairment, should be
      considered for their influence on care and outcomes. With these efforts,
      treatment risks can be minimized, and benefits can be placed within the health
      context of the elderly patient.

PMID- 17502592
TI  - Visual word processing and experiential origins of functional selectivity in
      human extrastriate cortex.
AB  - How do category-selective regions arise in human extrastriate cortex? Visually
      presented words provide an ideal test of the role of experience: Although
      individuals have extensive experience with visual words, our species has only
      been reading for a few thousand years, a period not thought to be long enough for
      natural selection to produce a genetically specified mechanism dedicated to
      visual word recognition per se. Using relatively high-resolution functional
      magnetic resonance imaging (1.4 x 1.4 x 2-mm voxels), we identified a small
      region of extrastriate cortex in most participants that responds selectively to
      both visually presented words and consonant strings, compared with line drawings,
      digit strings, and Chinese characters. Critically, we show that this pattern of
      selectivity is dependent on experience with specific orthographies: The same
      region responds more strongly to Hebrew words in Hebrew readers than in
      nonreaders of Hebrew. These results indicate that extensive experience with a
      given visual category can produce strong selectivity for that category in
      discrete cortical regions.

PMID- 17502593
TI  - Nanoparticles as catalysts for protein fibrillation.

PMID- 17502594
TI  - A highly divergent microsatellite facilitating fast and accurate DRB haplotyping
      in humans and rhesus macaques.
AB  - The DRB region of the MHC in primate species is known to display abundant region
      configuration polymorphism with regard to the number and content of genes present
      per haplotype. Furthermore, depending on the species studied, the different DRB
      genes themselves may display varying degrees of allelic polymorphism. Because of
      this combination of diversity (differential gene number) and polymorphism
      (allelic variation), molecular typing methods for the primate DRB region are
      cumbersome. All intact DRB genes present in humans and rhesus macaques appear to
      possess, however, a complex and highly divergent microsatellite. Microsatellite
      analysis of a sizeable panel of outbred rhesus macaques, covering most of the
      known Mamu-DRB haplotypes, resulted in the definition of unique genotyping
      patterns that appear to be specific for a given haplotype. Subsequent examination
      of a representative panel of human cells illustrated that this approach also
      facilitates high-resolution HLA-DRB typing in an easy, quick, and reproducible
      fashion. The genetic composition of this complex microsatellite is shown to be in
      concordance with the phylogenetic relationships of various HLA-DRB and Mamu-DRB
      exon 2 gene/lineage sequences. Moreover, its length variability segregates with
      allelic variation of the respective gene. This simple protocol may find
      application in a variety of research avenues such as transplantation biology,
      disease association studies, molecular ecology, paternity testing, and forensic
      medicine.

PMID- 17502595
TI  - A possible role for primary motor cortex during action observation.

PMID- 17502596
TI  - Ascorbate in pharmacologic concentrations selectively generates ascorbate radical
      and hydrogen peroxide in extracellular fluid in vivo.
AB  - Ascorbate (ascorbic acid, vitamin C), in pharmacologic concentrations easily
      achieved in humans by i.v. administration, selectively kills some cancer cells
      but not normal cells. We proposed that pharmacologic ascorbate is a prodrug for
      preferential steady-state formation of ascorbate radical (Asc(*-)) and H(2)O(2)
      in the extracellular space compared with blood. Here we test this hypothesis in
      vivo. Rats were administered parenteral (i.v. or i.p.) or oral ascorbate in
      typical human pharmacologic doses ( approximately 0.25-0.5 mg per gram of body
      weight). After i.v. injection, ascorbate baseline concentrations of 50-100 microM
      in blood and extracellular fluid increased to peaks of >8 mM. After i.p.
      injection, peaks approached 3 mM in both fluids. By gavage, the same doses
      produced ascorbate concentrations of <150 microM in both fluids. In blood, Asc(*
      ) concentrations measured by EPR were undetectable with oral administration and
      always <50 nM with parenteral administration, even when corresponding ascorbate
      concentrations were >8 mM. After parenteral dosing, Asc(*-) concentrations in
      extracellular fluid were 4- to 12-fold higher than those in blood, were as high
      as 250 nM, and were a function of ascorbate concentrations. By using the
      synthesized probe peroxyxanthone, H(2)O(2) in extracellular fluid was detected
      only after parenteral administration of ascorbate and when Asc(*-) concentrations
      in extracellular fluid exceeded 100 nM. The data show that pharmacologic
      ascorbate is a prodrug for preferential steady-state formation of Asc(*-) and
      H(2)O(2) in the extracellular space but not blood. These data provide a
      foundation for pursuing pharmacologic ascorbate as a prooxidant therapeutic agent
      in cancer and infections.

PMID- 17502597
TI  - Oribatid mites as a major dietary source for alkaloids in poison frogs.
AB  - Alkaloids in the skin glands of poison frogs serve as a chemical defense against
      predation, and almost all of these alkaloids appear to be sequestered from
      dietary arthropods. Certain alkaloid-containing ants have been considered the
      primary dietary source, but dietary sources for the majority of alkaloids remain
      unknown. Herein we report the presence of approximately 80 alkaloids from
      extracts of oribatid mites collected throughout Costa Rica and Panama, which
      represent 11 of the approximately 24 structural classes of alkaloids known in
      poison frogs. Forty-one of these alkaloids also occur in the dendrobatid poison
      frog, Oophaga pumilio, which co-occurs with the collected mites. These shared
      alkaloids include twenty-five 5,8-disubstituted or 5,6,8-trisubstituted
      indolizidines; one 1,4-disubstituted quinolizidine; three pumiliotoxins; and one
      homopumiliotoxin. All but the last of these alkaloid classes occur widely in
      poison frogs. In addition, nearly 40 alkaloids of unknown structure were detected
      in mites; none of these alkaloids have been identified in frog extracts. Two of
      these alkaloids are homopumiliotoxins, five appear to be izidines, four appear to
      be tricyclics, and six are related in structure to poison frog alkaloids that are
      currently unclassified as to structure. Mites are common in the diet of O.
      pumilio, as well as in the diets of other poison frogs. The results of this study
      indicate that mites are a significant arthropod repository of a variety of
      alkaloids and represent a major dietary source of alkaloids in poison frogs.

PMID- 17502598
TI  - Entrainment of the human circadian pacemaker to longer-than-24-h days.
AB  - Entrainment of the circadian pacemaker to the light:dark cycle is necessary for
      rhythmic physiological functions to be appropriately timed over the 24-h day.
      Nonentrainment results in sleep, endocrine, and neurobehavioral impairments.
      Exposures to intermittent bright light pulses have been reported to phase shift
      the circadian pacemaker with great efficacy. Therefore, we tested the hypothesis
      that a modulated light exposure (MLE) with bright light pulses in the evening
      would entrain subjects to a light:dark cycle 1 h longer than their own circadian
      period (tau). Twelve subjects underwent a 65-day inpatient study. Individual
      subject's circadian period was determined in a forced desynchrony protocol.
      Subsequently, subjects were released into 30 longer-than-24-h days (daylength of
      tau + 1 h) in one of three light:dark conditions: (i) approximately 25 lux; (ii)
      approximately 100 lux; and (iii) MLE: approximately 25 lux followed by
      approximately 100 lux, plus two 45-min bright light pulses of approximately 9,500
      lux near the end of scheduled wakefulness. We found that lighting levels of
      approximately 25 lux were insufficient to entrain all subjects tested. Exposure
      to approximately 100 lux was sufficient to entrain subjects, although at a
      significantly wider phase angle compared with baseline. Exposure to MLE was able
      to entrain the subjects to the imposed sleep-wake cycles but at a phase angle
      comparable to baseline. These results suggest that MLE can be used to entrain the
      circadian pacemaker to non-24-h days. The implications of these findings are
      important because they could be used to treat circadian misalignment associated
      with space flight and circadian rhythm sleep disorders such as shift-work
      disorder.

PMID- 17502599
TI  - A complex thiolate switch regulates the Bacillus subtilis organic peroxide sensor
      OhrR.
AB  - Oxidation of protein thiolates is central to numerous redox-regulated processes.
      Bacillus subtilis OhrR is an organic peroxide sensor that represses expression of
      an inducible peroxiredoxin, OhrA. Here, we present evidence that oxidation of the
      sole cysteine residue in OhrR leads to a sulfenic acid-containing intermediate
      that retains DNA-binding activity: further reaction to generate either a mixed
      disulfide (S-thiolation) or a protein sulfenamide (sulfenyl-amide) derivative is
      essential for derepression. Protein S-thiolation protects OhrR from overoxidation
      and provides for a facile regeneration of active OhrR by thiol-disulfide exchange
      reactions. The sulfenamide can also be reduced by thiol-disulfide exchange
      reactions, although this process is much slower than for mixed disulfides.
      Recovery of oxidized OhrR from B. subtilis identifies three distinct S-thiolated
      species, including mixed disulfides with a novel 398-Da thiol, cysteine, and
      CoASH. Evidence for in vivo formation of the sulfenamide derivative is also
      presented.

PMID- 17502600
TI  - Structural insights into the bactericidal mechanism of human peptidoglycan
      recognition proteins.
AB  - Peptidoglycan recognition proteins (PGRPs) are highly conserved pattern
      recognition molecules of the innate immune system that bind bacterial
      peptidoglycans (PGNs), which are polymers of alternating N-acetylglucosamine
      (NAG) and N-acetylmuramic acid (NAM) cross-linked by short peptide stems. Human
      PRGPs are bactericidal against pathogenic and nonpathogenic Gram-positive
      bacteria, but not normal flora bacteria. Like certain glycopeptide antibiotics
      (e.g., vancomycin), PGRPs kill bacteria by directly interacting with their cell
      wall PGN, thereby interfering with PGN maturation. To better understand the
      bactericidal mechanism of PGRPs, we determined the crystal structure of the C
      terminal PGN-binding domain of human PGRP-I beta in complex with NAG-NAM-L-Ala
      gamma-D-Glu-L-Lys-D-Ala-D-Ala, a synthetic glycopeptide comprising a complete PGN
      repeat. This structure, in conjunction with the previously reported NMR structure
      of a dimeric PGN fragment, permitted identification of major conformational
      differences between free and PGRP-bound PGN with respect to the relative
      orientation of saccharide and peptide moieties. These differences provided
      structural insights into the bactericidal mechanism of human PGRPs. On the basis
      of molecular modeling, we propose that these proteins disrupt cell wall
      maturation not only by sterically encumbering access of biosynthetic enzymes to
      the nascent PGN chains, but also by locking PGN into a conformation that prevents
      formation of cross-links between peptide stems in the growing cell wall.

PMID- 17502601
TI  - The human disease network.
AB  - A network of disorders and disease genes linked by known disorder-gene
      associations offers a platform to explore in a single graph-theoretic framework
      all known phenotype and disease gene associations, indicating the common genetic
      origin of many diseases. Genes associated with similar disorders show both higher
      likelihood of physical interactions between their products and higher expression
      profiling similarity for their transcripts, supporting the existence of distinct
      disease-specific functional modules. We find that essential human genes are
      likely to encode hub proteins and are expressed widely in most tissues. This
      suggests that disease genes also would play a central role in the human
      interactome. In contrast, we find that the vast majority of disease genes are
      nonessential and show no tendency to encode hub proteins, and their expression
      pattern indicates that they are localized in the functional periphery of the
      network. A selection-based model explains the observed difference between
      essential and disease genes and also suggests that diseases caused by somatic
      mutations should not be peripheral, a prediction we confirm for cancer genes.

PMID- 17502602
TI  - IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive
      functions, regulates N-type Ca2+-channel and neurite elongation.
AB  - Null mutations in the IL1-receptor accessory protein-like 1 gene (IL1RAPL1) are
      responsible for an inherited X-linked form of cognitive impairment. IL1RAPL1
      protein physically interacts with neuronal calcium sensor-1 (NCS-1), but the
      functional impact of the IL1RAPL1/NCS-1 interaction remains unknown. Here, we
      demonstrate that stable expression of IL1RAPL1 in PC12 cells induces a specific
      silencing of N-type voltage-gated calcium channels (N-VGCC) activity that
      explains a secretion deficit observed in these IL1RAPL1 cells. Importantly, this
      modulation of VGCC activity is mediated by NCS-1. Indeed, a specific loss-of
      function of N-VGCC was observed in PC12 cells overexpressing NCS-1, and a total
      recovery of N-VGCC activity was obtained by a down-regulation of NCS-1 in
      IL1RAPL1 cells. The functional relevance of the interaction between IL1RAPL1 and
      NCS-1 was also suggested by the reduction of neurite elongation observed in nerve
      growth factor (NGF)-treated IL1RAPL1 cells, a phenotype rescued by NCS-1
      inactivation. Because both proteins are highly expressed in neurons, these
      results suggest that IL1RAPL1-related mental retardation could result from a
      disruption of N-VGCC and/or NCS-1-dependent synaptic and neuronal activities.

PMID- 17502603
TI  - Single-molecule FRET reveals sugar-induced conformational dynamics in LacY.
AB  - The N- and C-terminal six-helix bundles of lactose permease (LacY) form a large
      internal cavity open on the cytoplasmic side and closed on the periplasmic side
      with a single sugar-binding site at the apex of the cavity near the middle of the
      molecule. During sugar/H(+) symport, an outward-facing cavity is thought to open
      with closing of the inward-facing cavity so that the sugar-binding site is
      alternately accessible to either face of the membrane. In this communication,
      single-molecule fluorescence (Forster) resonance energy transfer is used to test
      this model with wild-type LacY and a conformationally restricted mutant. Pairs of
      Cys residues at the ends of two helices on the cytoplasmic or periplasmic sides
      of wild-type LacY and the mutant were labeled with appropriate donor and acceptor
      fluorophores, single-molecule fluorescence resonance energy transfer was
      determined in the absence and presence of sugar, and distance changes were
      calculated. With wild-type LacY, binding of a galactopyranoside, but not a
      glucopyranoside, results in a decrease in distance on the cytoplasmic side and an
      increase in distance on the periplasmic side. In contrast, with the mutant, a
      more pronounced decrease in distance and in distance distribution is observed on
      the cytoplasmic side, but there is no change on the periplasmic side. The results
      are consistent with the alternating access model and indicate that the defect in
      the mutant is due to impaired ligand-induced flexibility on the periplasmic side.

PMID- 17502604
TI  - Automated 2D IR spectroscopy using a mid-IR pulse shaper and application of this
      technology to the human islet amyloid polypeptide.
AB  - The capability of 2D IR spectroscopy to elucidate time-evolving structures is
      enhanced by a programmable mid-IR pulse shaper that greatly improves the ease,
      speed, and accuracy of data collection. Traditional ways of collecting 2D IR
      spectra are difficult to implement, cause distorted peak shapes, and result in
      poor time resolution and/or phase problems. We report on several methods for
      collecting 2D IR spectra by using a computer-controlled germanium acoustooptic
      modulator that overcomes the above problems. The accuracy and resolution of each
      method is evaluated by using model metal carbonyl compounds that have well
      defined lineshapes. Furthermore, phase cycling can now be employed to largely
      alleviate background scatter from heterogeneous samples. With these methods in
      hand, we apply 2D IR spectroscopy to study the structural diversity in amyloid
      fibers of aggregated human islet amyloid polypeptide (hIAPP), which is involved
      with type 2 diabetes. The 2D IR spectra reveal that the beta-sheet fibers have a
      large structural distribution, as evidenced by an inhomogeneously broadened beta
      sheet peak and strong coupling to random coil conformations. Structural diversity
      is an important characteristic of hIAPP because it may be that partly folded
      peptides cause the disease. This experiment on hIAPP is an example of how
      computer generation of 2D IR pulse sequences is a key step toward automating 2D
      IR spectroscopy, so that new pulse sequences can be implemented quickly and a
      diverse range of systems can be studied more easily.

PMID- 17502605
TI  - Retrograde nuclear accumulation of cytoplasmic tRNA in rat hepatoma cells in
      response to amino acid deprivation.
AB  - Until recently, transport of tRNA was presumed to be unidirectional, from the
      nucleus to the cytoplasm. Our published findings, however, revealed that
      cytoplasmic tRNAs move retrograde to the nucleus in Saccharomyces cerevisiae and
      that nuclear accumulation of cytoplasmic tRNAs occurs when cells are nutrient
      deprived. The findings led us to examine whether retrograde nuclear accumulation
      of cytoplasmic tRNAs occurs in higher eukaryotes. Using RNA FISH and Northern and
      Western analyses we show that tRNAs accumulate in nuclei of a hepatoma cell line
      in response to amino acid deprivation. To discern whether tRNA nuclear
      accumulation results from nuclear import of cytoplasmic tRNAs, transcription of
      new RNAs was inhibited, and the location of "old" tRNAs in response to nutrient
      stress was determined. Even in the absence of new RNA synthesis, there were
      significant tRNA nuclear pools after amino acid depletion, providing strong
      evidence that retrograde traffic is responsible for the tRNA nuclear pools.
      Further analyses showed that retrograde tRNA nuclear accumulation in hepatoma
      cells is a reversible and energy-dependent process. The data provide evidence for
      retrograde tRNA nuclear accumulation in intact mammalian cells and support the
      hypothesis that nuclear accumulation of cytoplasmic tRNA and tRNA re-export to
      the cytoplasm may constitute a universal mechanism for posttranscriptional
      regulation of global gene expression in response to nutrient availability.

PMID- 17502606
TI  - Bacteria of the genus Asaia stably associate with Anopheles stephensi, an Asian
      malarial mosquito vector.
AB  - Here, we show that an alpha-proteobacterium of the genus Asaia is stably
      associated with larvae and adults of Anopheles stephensi, an important mosquito
      vector of Plasmodium vivax, a main malaria agent in Asia. Asaia bacteria dominate
      mosquito-associated microbiota, as shown by 16S rRNA gene abundance, quantitative
      PCR, transmission electron microscopy and in situ-hybridization of 16S rRNA
      genes. In adult mosquitoes, Asaia sp. is present in high population density in
      the female gut and in the male reproductive tract. Asaia sp. from An. stephensi
      has been cultured in cell-free media and then transformed with foreign DNA. A
      green fluorescent protein-tagged Asaia sp. strain effectively lodged in the
      female gut and salivary glands, sites that are crucial for Plasmodium sp.
      development and transmission. The larval gut and the male reproductive system
      were also colonized by the transformed Asaia sp. strain. As an efficient
      inducible colonizer of mosquitoes that transmit Plasmodium sp., Asaia sp. may be
      a candidate for malaria control.

PMID- 17502607
TI  - A climate-driven switch in plant nitrogen acquisition within tropical forest
      communities.
AB  - The response of tropical forests to climate change will depend on individual
      plant species' nutritional strategies, which have not been defined in the case of
      the nitrogen nutrition that is critical to sustaining plant growth and
      photosynthesis. We used isotope natural abundances to show that a group of
      tropical plant species with diverse growth strategies (trees and ferns, canopy,
      and subcanopy) relied on a common pool of inorganic nitrogen, rather than
      specializing on different nitrogen pools. Moreover, the tropical species we
      examined changed their dominant nitrogen source abruptly, and in unison, in
      response to precipitation change. This threshold response indicates a coherent
      strategy among species to exploit the most available form of nitrogen in soils.
      The apparent community-wide flexibility in nitrogen uptake suggests that diverse
      species within tropical forests can physiologically track changes in nitrogen
      cycling caused by climate change.

PMID- 17502608
TI  - Role of Peyer's patches in the induction of Helicobacter pylori-induced
      gastritis.
AB  - Helicobacter pylori is a Gram-negative spiral bacterium that causes gastritis and
      peptic ulcer and has been implicated in the pathogenesis of gastric
      adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Although Th1
      immunity is involved in gastritis and the accumulation of H. pylori-specific
      CD4(+) T cells in the H. pylori-infected gastric mucosa in human patients, how T
      cells are primed with H. pylori antigens is unknown because no apparent lymphoid
      tissues are present in the stomach. We demonstrate here that Peyer's patches
      (PPs) in the small intestine play critical roles in H. pylori-induced gastritis;
      no gastritis is induced in H. pylori-infected mice lacking PPs. We also observed
      that the coccoid form of H. pylori is phagocytosed by dendritic cells in PPs. We
      propose that H. pylori converts to the coccoid form in the anaerobic small
      intestine and stimulates the host immune system through PPs.

PMID- 17502609
TI  - Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected
      cells interferes with stress granule formation and processing body assembly.
AB  - The West Nile virus minus-strand 3' terminal stem loop (SL) RNA was previously
      shown to bind specifically to cellular stress granule (SG) components, T cell
      intracellular antigen-1 (TIA-1) and the related protein TIAR. In vitro TIAR
      binding was 10 times more efficient than TIA-1. The 3'(-)SL functions as the
      promoter for genomic RNA synthesis. Colocalization of TIAR and TIA-1 with the
      viral replication complex components dsRNA and NS3 was observed in the
      perinuclear regions of West Nile virus- and dengue virus-infected cells. The
      kinetics of accumulation of TIAR in the perinuclear region was similar to those
      of genomic RNA synthesis. In contrast, relocation of TIA-1 to the perinuclear
      region began only after maximal levels of RNA synthesis had been achieved, except
      when TIAR was absent. Virus infection did not induce SGs and progressive
      resistance to SG induction by arsenite developed coincident with TIAR relocation.
      A progressive decrease in the number of processing bodies was secondarily
      observed in infected cells. These data suggest that the interaction of TIAR with
      viral components facilitates flavivirus genome RNA synthesis and inhibits SG
      formation, which prevents the shutoff of host translation.

PMID- 17502610
TI  - Double proton transfer dynamics of model DNA base pairs in the condensed phase.
AB  - The dynamics of excited-state double proton transfer of model DNA base pairs, 7
      azaindole dimers, is reported using femtosecond fluorescence spectroscopy. To
      elucidate the nature of the transfer in the condensed phase, here we examine
      variation of solvent polarity and viscosity, solute concentration, and isotopic
      fractionation. The rate of proton transfer is found to be significantly dependent
      on polarity and on the isotopic composition in the pair. Consistent with a
      stepwise mechanism, the results support the presence of an ionic intermediate
      species which forms on the femtosecond time scale and decays to the final
      tautomeric form on the picosecond time scale. We discuss the results in relation
      to the molecular motions involved and comment on recent claims of concerted
      transfer in the condensed phase. The nonconcerted mechanism is in agreement with
      previous isolated-molecule femtosecond dynamics and is also consistent with the
      most-recent high-level theoretical study on the same pair.

PMID- 17502611
TI  - Trans-SNARE complex assembly and yeast vacuole membrane fusion.
AB  - cis-SNARE complexes (anchored in one membrane) are disassembled by Sec17p (alpha
      SNAP) and Sec18p (NSF), permitting the unpaired SNAREs to assemble in trans. We
      now report a direct assay of trans-SNARE complex formation during yeast vacuole
      docking. SNARE complex assembly and fusion is promoted by high concentrations of
      the SNARE Vam7p or Nyv1p or by addition of HOPS (homotypic fusion and vacuole
      protein sorting), a Ypt7p (Rab)-effector complex with a Sec1/Munc18-family
      subunit. Inhibitors that target Ypt7p, HOPS, or key regulatory lipids prevent
      trans-SNARE complex assembly and ensuing fusion. Strikingly, the lipid ligand MED
      (myristoylated alanine-rich C kinase substrate effector domain) or elevated
      concentrations of Sec17p, which can displace HOPS from SNARE complexes, permit
      full trans-SNARE pairing but block fusion. These findings suggest that efficient
      fusion requires trans-SNARE complex associations with factors such as HOPS and
      subsequent regulated lipid rearrangements.

PMID- 17502612
TI  - A role for exposed mannosylations in presentation of human therapeutic self
      proteins to CD4+ T lymphocytes.
AB  - Several therapeutic self-proteins elicit immune responses when administered to
      patients. Such adverse immune responses reduce drug efficacy. To induce an immune
      response, a protein must interact with different immune cells, including antigen
      presenting cells, T cells, and B cells. Each cell type recognizes distinct
      immunogenic patterns on antigens. Mannose-terminating glycans have been
      identified as pathogen-associated molecular patterns that are essential for
      internalization of microbes by antigen-presenting cells, leading to presentation.
      Here, we have investigated the importance of exposed mannosylation on an
      immunogenic therapeutic self-protein, procoagulant human factor VIII (FVIII).
      Administration of therapeutic FVIII to hemophilia A patients induces inhibitory
      anti-FVIII antibodies in up to 30% of the cases. We demonstrate that entry of
      FVIII into human dendritic cells (DC) leading to T cell activation, is mediated
      by mannose-terminating glycans on FVIII. Further, we identified macrophage
      mannose receptor (CD206) as a candidate endocytic receptor for FVIII on DC.
      Saturation of mannose receptors on DC with mannan, and enzymatic removal of
      mannosylated glycans from FVIII lead to reduced T cell activation. The
      interaction between FVIII and CD206 was blocked by VWF, suggesting that, under
      physiological conditions, the intrinsic mannose-dependent immunogenicity of FVIII
      is quenched by endogenous immunochaperones. These data provide a link between the
      mannosylation of therapeutic self-proteins and their iatrogenic immunogenicity.
      Such a link would be of special relevance in the context of replacement therapy
      where mechanisms of central and peripheral tolerance have not been established
      during ontogeny because of the absence of the antigen.

PMID- 17502613
TI  - In vitro erythropoiesis from bone marrow-derived progenitors provides a
      physiological assay for toxic and mutagenic compounds.
AB  - The goal of this study was to create an in vitro cell culture system that
      captures essential features of the in vivo erythroid micronucleus (MN)
      genotoxicity assay, thus enabling increased throughput and controlled studies of
      the hematopoietic DNA damage response. We show that adult bone marrow (BM)
      cultures respond to erythropoietin, the principal hormone that stimulates
      erythropoiesis, with physiological erythropoietic proliferation, differentiation,
      and enucleation. We then show that this in vitro erythropoietic system clearly
      signals exposure to genotoxicants through erythroid MN formation. Furthermore, we
      determined that DNA repair-deficient (MGMT(-/-)) BM displayed sensitivity to
      genotoxic exposure in vivo compared with WT BM and that this phenotypic response
      was reflected in erythropoietic cultures. These findings suggest that this in
      vitro erythroid MN assay is capable of screening for genotoxicity on BM in a
      physiologically reflective manner. Finally, responses to genotoxicants during
      erythroid differentiation varied with exposure time, demonstrating that this
      system can be used to study the effect of DNA damage at specific developmental
      stages.

PMID- 17502614
TI  - Exposing the core promoter is sufficient to activate transcription and alter
      coactivator requirement at RNR3.
AB  - Chromatin is a formidable barrier to transcription. Nucleosome density is lowest
      over the regulatory regions of active genes, and many repressed genes have a
      tightly positioned nucleosome over their core promoter. However, it has not been
      shown that nucleosome positioning is sufficient for repression or whether
      disrupting a core promoter nucleosome specifically can activate gene expression
      in the absence of activating signals. Here we show that disrupting the nucleosome
      over the core promoter of RNR3 is sufficient to drive preinitiation complex
      assembly and activate transcription in the absence of activating signals.
      Remodeling of chromatin over the RNR3 promoter requires the recruitment of the
      SWI/SNF complex by the general transcription factor TFIID. We found that
      disrupting the nucleosome over the RNR3 core promoter relieves its dependence on
      TFIID and SWI/SNF, indicating a functional link between these two complexes.
      These results suggest that the specific function of TAF(II)s is to direct the
      chromatin remodeling step through SWI/SNF recruitment, and not core promoter
      selectivity. Our results indicate that nucleosome placement plays a dominant role
      in repression and that the ability of the core promoter to position a nucleosome
      is a major determinant in TAF(II) dependency of genes in vivo.

PMID- 17502615
TI  - Functionally distinct genes regulated by hydrogen limitation and growth rate in
      methanogenic Archaea.
AB  - The use of molecular hydrogen as electron donor for energy generation is a
      defining characteristic of the hydrogenotrophic methanogens, an ancient group
      that dominates the phylum Euryarchaeota. We present here a global study of
      changes in mRNA abundance in response to hydrogen availability for a
      hydrogenotrophic methanogen. Cells of Methanococcus maripaludis were grown by
      using continuous culture to deconvolute the effects of hydrogen limitation and
      growth rate, and microarray analyses were conducted. Hydrogen limitation markedly
      increased mRNA levels for genes encoding enzymes of the methanogenic pathway that
      reduce or oxidize the electron-carrying deazaflavin, coenzyme F(420). F(420)
      dependent redox functions in energy-generating metabolism are characteristic of
      the methanogenic Archaea, and the results show that their regulation is distinct
      from other redox processes in the cell. Rapid growth increased mRNA levels of the
      gene for an unusual hydrogenase, the hydrogen-dependent
      methylenetetrahydromethanopterin dehydrogenase.

PMID- 17502616
TI  - "Diminishing returns" in the scaling of functional leaf traits across and within
      species groups.
AB  - More than 5,000 measurements from 1,943 plant species were used to explore the
      scaling relationships among the foliar surface area and the dry, water, and
      nitrogen/phosphorus mass of mature individual leaves. Although they differed
      statistically, the exponents for the relationships among these variables were
      numerically similar among six species groups (ferns, graminoids, forbs, shrubs,
      trees, and vines) and within 19 individual species. In general, at least one
      among the many scaling exponents was <1.0, such that increases in one or more
      features influencing foliar function (e.g., surface area or living leaf mass)
      failed to keep pace with increases in mature leaf size. Thus, a general set of
      scaling relationships exists that negatively affects increases in leaf size. We
      argue that this set reflects a fundamental property of all plants and helps to
      explain why annual growth fails to keep pace with increases in total body mass
      across species.

PMID- 17502617
TI  - Construction and behavior of engineered minichromosomes in maize.
AB  - Engineered minichromosomes were constructed in maize by modifying natural A and
      supernumerary B chromosomes. By using telomere-mediated chromosomal truncation,
      it was demonstrated that such an approach is feasible for the generation of
      minichromosomes of normal A chromosomes by selection of spontaneous polyploid
      events that compensate for the deficiencies produced. B chromosomes are readily
      fractionated by biolistic transformation of truncating plasmids. Foreign genes
      were faithfully expressed from integrations into normal B chromosomes and from
      truncated miniB chromosomes. Site-specific recombination between the terminal
      transgene on a miniA chromosome and a terminal site on a normal chromosome was
      demonstrated. It was also found that the miniA chromosome did not pair with its
      progenitor chromosomes during meiosis, indicating a useful property for such
      constructs. The miniB chromosomes are faithfully transmitted from one generation
      to the next but can be changed in dosage in the presence of normal B chromosomes.
      This approach for construction of engineered chromosomes can be easily extended
      to other plant species because it does not rely on cloned centromere sequences,
      which are species-specific. These platforms will provide avenues for studies on
      plant chromosome structure and function and for future developments in
      biotechnology and agriculture.

PMID- 17502618
TI  - Matching phylogeny and metabolism in the uncultured marine bacteria, one cell at
      a time.
AB  - The identification of predominant microbial taxa with specific metabolic
      capabilities remains one the biggest challenges in environmental microbiology,
      because of the limits of current metagenomic and cell culturing methods. We
      report results from the direct analysis of multiple genes in individual marine
      bacteria cells, demonstrating the potential for high-throughput metabolic
      assignment of yet-uncultured taxa. The protocol uses high-speed fluorescence
      activated cell sorting, whole-genome multiple displacement amplification (MDA),
      and subsequent PCR screening. A pilot library of 11 single amplified genomes
      (SAGs) was constructed from Gulf of Maine bacterioplankton as proof of concept.
      The library consisted of five flavobacteria, one sphingobacterium, four
      alphaproteobacteria, and one gammaproteobacterium. Most of the SAGs, apart from
      alphaproteobacteria, were phylogenetically distant from existing isolates, with
      88-97% identity in the 16S rRNA gene sequence. Thus, single-cell MDA provided
      access to the genomic material of numerically dominant but yet-uncultured
      taxonomic groups. Two of five flavobacteria in the SAG library contained
      proteorhodopsin genes, suggesting that flavobacteria are among the major carriers
      of this photometabolic system. The pufM and nasA genes were detected in some 100
      cell MDA products but not in SAGs, demonstrating that organisms containing
      bacteriochlorophyll and assimilative nitrate reductase constituted <1% of the
      sampled bacterioplankton. Compared with metagenomics, the power of our approach
      lies in the ability to detect metabolic genes in uncultured microorganisms
      directly, even when the metabolic and phylogenetic markers are located far apart
      on the chromosome.

PMID- 17502619
TI  - beta-Actin regulates platelet nitric oxide synthase 3 activity through
      interaction with heat shock protein 90.
AB  - Cytoskeletal proteins are crucial in maintaining cellular structure and, in
      certain cell types, also play an essential role in motility and shape change.
      Nitric oxide (NO) is an important paracrine mediator of vascular and platelet
      function and is produced in the vasculature by the enzyme NO synthase type 3 (NOS
      3). Here, we demonstrate in human platelets that the polymerization state of beta
      actin crucially regulates the activation state of NOS-3, and hence NO formation,
      through altering its binding of heat shock protein 90 (Hsp90). We found that NOS
      3 binds to the globular, but not the filamentous, form of beta-actin, and the
      affinity of NOS-3 for globular beta-actin is, in turn, increased by Hsp90.
      Formation of this ternary complex among NOS-3, globular beta-actin, and Hsp90, in
      turn, results in an increase in both NOS activity and cyclic guanosine-3',5'
      monophosphate, an index of bioactive NO, as well as an increased rate of Hsp90
      degradation, thus limiting the duration for which NOS-3 remains activated. These
      observations suggest that beta-actin plays a critical role in regulating NO
      formation and signaling in platelets.

PMID- 17502620
TI  - Photodynamic molecular beacon as an activatable photosensitizer based on protease
      controlled singlet oxygen quenching and activation.
AB  - Molecular beacons are FRET-based target-activatable probes. They offer control of
      fluorescence emission in response to specific cancer targets, thus are useful
      tools for in vivo cancer imaging. Photodynamic therapy (PDT) is a cell-killing
      process by light activation of a photosensitizer (PS) in the presence of oxygen.
      The key cytotoxic agent is singlet oxygen ((1)O(2)). By combining these two
      principles (FRET and PDT), we have introduced a concept of photodynamic molecular
      beacons (PMB) for controlling the PS's ability to generate (1)O(2) and,
      ultimately, for controlling its PDT activity. The PMB comprises a disease
      specific linker, a PS, and a (1)O(2) quencher, so that the PS's photoactivity is
      silenced until the linker interacts with a target molecule, such as a tumor
      associated protease. Here, we report the full implementation of this concept by
      synthesizing a matrix metalloproteinase-7 (MMP7)-triggered PMB and achieving not
      only MMP7-triggered production of (1)O(2) in solution but also MMP7-mediated
      photodynamic cytotoxicity in cancer cells. Preliminary in vivo studies also
      reveal the MMP7-activated PDT efficacy of this PMB. This study validates the core
      principle of the PMB concept that selective PDT-induced cell death can be
      achieved by exerting precise control of the PS's ability to produce (1)O(2) by
      responding to specific cancer-associated biomarkers. Thus, PDT selectivity will
      no longer depend solely on how selectively the PS can be delivered to cancer
      cells. Rather, it will depend on how selective a biomarker is to cancer cells,
      and how selective the interaction of PMB is to this biomarker.

PMID- 17502621
TI  - The frequency and structure of recombinant products is determined by the cellular
      level of MutL.
AB  - The presence of repeated DNA sequences is a genomic liability, because
      interrepeat recombination can result in chromosomal rearrangements. The mismatch
      repair system prevents recombination between nonidentical repeats, but the
      mechanism of antirecombination has not been established. Although the MutS
      protein binds to base pair mismatches in heteroduplex DNA, the role of the MutL
      protein in preventing recombination is unknown. In a screen designed to identify
      new cellular functions that suppress deletion formation involving nonidentical
      DNA repeats, we isolated a mutL mutant having a separation-of-function phenotype.
      The mutant showed an increased frequency of deletions but not of mutations. The
      split phenotype is due to a decreased MutL level, indicating that recombination,
      but not replication editing, is highly sensitive to MutL level. By altering the
      MutL level, we found that the frequency of deletion-generating recombination is
      inversely related to the amount of cellular MutL. DNA sequence analysis of the
      recombined repeats shows that the tolerance of base pair mismatches in
      heteroduplex DNA is also inversely correlated with MutL level. Unlike
      recombination, correction of misincorporation errors by mismatch repair is
      insensitive to fluctuations in MutL level. Overproduction of MutS does not affect
      either of these phenotypes, suggesting that, unlike MutL, MutS is not limiting
      for mismatch repair activities. These results indicate that MutL (i) determines
      effective DNA homology in recombination processes and (ii) fine tunes the process
      of deletion formation involving repeated, diverged DNA sequences.

PMID- 17502622
TI  - Proline-rich Gla protein 2 is a cell-surface vitamin K-dependent protein that
      binds to the transcriptional coactivator Yes-associated protein.
AB  - Proline-rich Gla protein 2 (PRGP2) is one of four known vertebrate transmembrane
      gamma-carboxyglutamic acid (Gla) proteins. Members of this protein family are
      broadly expressed in fetal and adult human tissues and share a common
      architecture consisting of a predicted propeptide and Gla domain, a single-pass
      transmembrane segment, and tandem Pro/Leu-Pro-Xaa-Tyr (PY) motifs near their C
      termini. Using a methodology developed for the regulated expression of
      enzymatically biotinylated proteins in mammalian cells, we demonstrate that PRGP2
      undergoes gamma-glutamyl carboxylation in a manner that is both dependent upon
      the presence of a proteolytically cleavable propeptide and sensitive to warfarin,
      a vitamin K antagonist that is widely used as an antithrombotic agent. When
      expressed at physiologically relevant levels, the majority of PRGP2 is present in
      the gamma-glutamyl carboxylated, propeptide-cleaved (mature) form. We
      additionally demonstrate, by Western blotting and flow cytometry, that mature
      PRGP2 is predominantly located on the cell surface with the Gla domain exposed
      extracellularly. In a yeast two-hybrid screen that used the C-terminal
      cytoplasmic region of PRGP2 as bait, we identified the WW domain-containing
      transcriptional coactivator Yes-associated protein (YAP) as a binding partner for
      PRGP2. In GST pull-down experiments, both PRGP2 PY motifs and both YAP WW domains
      were essential for complex formation, as were residues proximal to the core
      sequence of the first PY motif. These findings suggest that PRGP2 may be involved
      in a signal transduction pathway, the impairment of which may be an unintended
      consequence of warfarin therapy.

PMID- 17502623
TI  - Irreducible imprecision in atmospheric and oceanic simulations.
AB  - Atmospheric and oceanic computational simulation models often successfully depict
      chaotic space-time patterns, flow phenomena, dynamical balances, and equilibrium
      distributions that mimic nature. This success is accomplished through necessary
      but non-unique choices for discrete algorithms, parameterizations, and coupled
      contributing processes that introduce structural instability into the model.
      Therefore, we should expect a degree of irreducible imprecision in quantitative
      correspondences with nature, even with plausibly formulated models and careful
      calibration (tuning) to several empirical measures. Where precision is an issue
      (e.g., in a climate forecast), only simulation ensembles made across
      systematically designed model families allow an estimate of the level of relevant
      irreducible imprecision.

PMID- 17502624
TI  - Lightening up the UV response by identification of the arylhydrocarbon receptor
      as a cytoplasmatic target for ultraviolet B radiation.
AB  - UVB radiation-induced signaling in mammalian cells involves two major pathways:
      one that is initiated through the generation of DNA photoproducts in the nucleus
      and a second one that occurs independently of DNA damage and is characterized by
      cell surface receptor activation. The chromophore for the latter one has been
      unknown. Here, we report that the UVB response involves tryptophan as a
      chromophore. We show that through the intracellular generation of photoproducts,
      such as the arylhydrocarbon receptor (AhR) ligand 6-formylindolo[3,2-b]carbazole,
      signaling events are initiated, which are transferred to the nucleus and the cell
      membrane via activation of the cytoplasmatic AhR. Specifically, AhR activation by
      UVB leads to (i) transcriptional induction of cytochrome P450 1A1 and (ii) EGF
      receptor internalization with activation of the EGF receptor downstream target
      ERK1/2 and subsequent induction of cyclooxygenase-2. The role of the AhR in the
      UVB stress response was confirmed in vivo by studies employing AhR KO mice.

PMID- 17502626
TI  - Metabolomics: available results, current research projects in breast cancer, and
      future applications.
AB  - Metabolomics is the newest "omics" science. It is a dynamic portrait of the
      metabolic status of living systems. Metabolomics has brought new insights on
      metabolic fluxes and a more comprehensive and holistic understanding of a cell's
      environment. This burgeoning field promises to be a potential tool to fill the
      gap between genotype and phenotype. As its preceding "omics" sciences (ie,
      genomics and proteomics), metabolomics' aim is to dredge information hidden in a
      sea of data. This technology permits simultaneous monitoring of many hundreds, or
      thousands, of macro- and small molecules, as well as functional monitoring of
      multiple pivotal cellular pathways. In addition, elucidation of cellular
      responses to molecular damage, including evolutionarily conserved inducible
      molecular defense systems, could be achieved with metabolomics and could lead to
      the discovery of new biomarkers of molecular responses to functional
      perturbations. If metabolomic information could be translated into diagnostic
      tests, it might have the potential to impact on clinical practice, and it might
      lead to the supplementation of traditional biomarkers of cellular integrity, cell
      and tissue homeostasis, and morphological alterations that result from cell
      damage or death. In this review the concept and characteristics of metabolomics
      are introduced. Main current applications of metabolomics in cancer research are
      reviewed, including its potential in the drug discovery field, and, last but not
      least, its potential impact in the field of monitoring response and toxicity to
      anticancer agents. In the last section, research projects ongoing at our
      institution and future challenges for metabolomics will be presented and briefly
      discussed.

PMID- 17502625
TI  - A solution NMR study showing that active site ligands and nucleotides directly
      perturb the allosteric equilibrium in aspartate transcarbamoylase.
AB  - The 306-kDa aspartate transcarbamoylase is a well studied regulatory enzyme, and
      it has emerged as a paradigm for understanding allostery and cooperative binding
      processes. Although there is a consensus that the cooperative binding of active
      site ligands follows the Monod-Wyman-Changeux (MWC) model of allostery, there is
      some debate about the binding of effectors such as ATP and CTP and how they
      influence the allosteric equilibrium between R and T states of the enzyme. In
      this article, the binding of substrates, substrate analogues, and nucleotides is
      studied, along with their effect on the R-T equilibrium by using highly
      deuterated, (1)H,(13)C-methyl-labeled protein in concert with methyl-transverse
      relaxation optimized spectroscopy (TROSY) NMR. Although only the T state of the
      enzyme can be observed in spectra of wild-type unliganded aspartate
      transcarbamoylase, binding of active-site substrates shift the equilibrium so
      that correlations from the R state become visible, allowing the equilibrium
      constant (L') between ligand-saturated R and T forms of the enzyme to be measured
      quantitatively. The equilibrium constant between unliganded R and T forms (L)
      also is obtained, despite the fact that the R state is "invisible" in spectra, by
      means of an indirect process that makes use of relations that emerge from the
      fact that ligand binding and the R-T equilibrium are linked. Titrations with
      MgATP unequivocally establish that its binding directly perturbs the R-T
      equilibrium, consistent with the Monod-Wyman-Changeux model. This study
      emphasizes the utility of modern solution NMR spectroscopy in understanding
      protein function, even for systems with aggregate molecular masses in the
      hundreds of kilodaltons.

PMID- 17502627
TI  - Long-term follow-up of a randomized trial comparing concurrent single agent
      cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic
      irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group
      Study.
AB  - PURPOSE: We report the long-term survival and toxicity of a randomized phase III
      study comparing cisplatin alone with cisplatin, flurouracil, and hydroxyurea
      versus hydroxyurea concurrent with pelvic irradiation for patients with locally
      advanced cervical cancer with pathologically negative para-aortic nodes. PATIENTS
      AND METHODS: Comparisons of progression-free (PFS) and overall survival (OS)
      between treatment arms utilized Kaplan-Meier and log-rank statistics. Relative
      risk estimates adjusting for prognostic factors were determined using the Cox
      proportional hazards regression model. Pearson's 2 test was used to assess
      differences in adverse events. RESULTS: The analysis included 526 patients. The
      median follow-up among surviving patients was 106 months. Consistent with the
      original report, improvement in PFS and OS was evident for both cisplatin
      containing arms compared with hydroxyurea (P < .001). Analogous results were seen
      for stage IIB and for stage III disease (each P < .025). The relative risk of
      progression of disease or death was 0.57 (95% CI, 0.43 to 0.75) with cisplatin
      and 0.51 (95% CI, 0.38 to 0.67) with cisplatin-based combination chemotherapy
      compared with hydroxyurea. Among 518 patients who received radiation, acute
      (grade 3 or 4) gastrointestinal or urologic toxicities occurred in 66 with
      cisplatin (19.1%) and 29 with hydroxyurea (16.8%). Delayed radiation toxicity
      occurred in six patients who received cisplatin (1.7%) and two who received
      hydroxyurea (1.2%; P = .680). CONCLUSION: Cisplatin-based chemotherapy during
      pelvic radiation therapy improves long-term PFS and OS among locally advanced
      cervical cancer patients collectively and for stage IIB and III disease,
      individually. There was no observed increase in late toxicity with cisplatin
      based chemoradiotherapy.

PMID- 17502628
TI  - Summaries for patients. Depression care management and death among older persons
      with depression.

PMID- 17502630
TI  - A sustained mortality benefit from screening for abdominal aortic aneurysm.
AB  - BACKGROUND: Longer-term mortality benefit and cost-effectiveness for abdominal
      aortic aneurysm (AAA) screening are uncertain. OBJECTIVE: To estimate the
      benefits, in terms of AAA-related and all-cause mortality, and cost-effectiveness
      of ultrasonography screening for AAA in a group that was invited to screening
      compared with a group that was not invited at a mean 7-year follow-up. DESIGN:
      Randomized trial. SETTING: 4 centers in the United Kingdom. PATIENTS: Population
      based sample of 67,770 men age 65 to 74 years. INTERVENTION: Patients with an AAA
      detected at screening had surveillance and were offered surgery after predefined
      criteria were met. MEASUREMENTS: Mortality data were obtained after flagging on
      the national database. Unit costs obtained from large samples were applied to
      individual event data for the cost analysis. RESULTS: The hazard ratio was 0.53
      (95% CI, 0.42 to 0.68) for AAA-related mortality in the group invited for
      screening. The rupture rate in men with normal results on initial ultrasonography
      has remained low: 0.54 rupture (CI, 0.25 to 1.02 ruptures) per 10 000 person
      years. In terms of all-cause mortality, the observed hazard ratio was 0.96 (CI,
      0.93 to 1.00). At the 7-year follow-up, cost-effectiveness was estimated at $19
      500 (CI, $12,400 to $39,800) per life-year gained based on AAA-related mortality
      and $7600 (CI, $3300 to infinity) per life-year gained based on all-cause death.
      (All values are reported in U.S. dollars [U.K. 1 pound sterling = U.S. $1.58]).
      LIMITATION: Inclusion of deaths from aortic aneurysm at an unspecified site,
      which may include some thoracic aortic aneurysms, may have underestimated the
      treatment effect. CONCLUSIONS: These results from a large, pragmatic randomized
      trial show that the early mortality benefit of screening ultrasonography for AAA
      is maintained in the longer term and that the cost-effectiveness of screening
      improves over time. International Standard Randomized Controlled Trial
      registration number: ISRCTN37381646.

PMID- 17502629
TI  - The effect of a primary care practice-based depression intervention on mortality
      in older adults: a randomized trial.
AB  - BACKGROUND: Few studies have tested the effects of a depression intervention on
      the risk for death associated with depression. OBJECTIVE: To test whether an
      intervention to improve depression care can modify the risk for death. DESIGN:
      Practice-based, randomized, controlled trial. SETTING: 20 primary care practices
      in New York, New York, and Philadelphia and Pittsburgh, Pennsylvania. PATIENTS:
      1226 randomly sampled patients identified through a 2-stage, age-stratified (60
      to 74 years and > or =75 years) depression screening. INTERVENTION: Depression
      care manager working with primary care physicians to provide algorithm-based
      care. MEASUREMENTS: Depression status based on clinical interview and vital
      status at 5 years by using the National Death Index. RESULTS: At baseline, 396
      patients met criteria for major depression and 203 patients met criteria for
      clinically significant minor depression. After a median follow-up of 52.8 months,
      223 patients died. Patients with depression in intervention practices were less
      likely to have died than those in usual care practices (adjusted hazard ratio,
      0.67 [95% CI, 0.44 to 1.00]). Risk for death was reduced in patients with major
      depression (adjusted hazard ratio, 0.55 [CI, 0.36 to 0.84]) but not in patients
      with clinically significant minor depression (adjusted hazard ratio, 0.97 [CI,
      0.49 to 1.92]). The benefit seemed to be almost entirely attributable to a
      reduction in deaths due to cancer. LIMITATIONS: The mechanism for an effect on
      deaths due to cancer is unclear. Depression status, cause of death, and vital
      status might have been misclassified. CONCLUSIONS: Older primary care patients
      with major depression in practices that implemented depression care management
      were less likely to die over a 5-year period than were patients with major
      depression in usual care practices. The effect seemed to be limited to deaths due
      to cancer. The mechanism for such an effect is unclear and warrants further
      investigation. ClinicalTrials.gov registration number: NCT00000367.

PMID- 17502631
TI  - Differences in access to liver transplantation: disease severity, waiting time,
      and transplantation center volume.
AB  - BACKGROUND: The Model for End-Stage Liver Disease (MELD) score has been used
      since February 2002 to allocate livers for transplantation from deceased donors
      according to medical need. Allocation based on MELD scores should ensure that
      sicker patients receive transplants first regardless of transplantation center
      volume. OBJECTIVE: To determine whether the MELD score at transplantation and
      waiting time of liver transplant recipients differs by transplantation center
      volume. DESIGN: Analysis of the Organ Procurement and Transplantation Network
      database. Centers were classified according to the volume of transplantations
      performed in 2005: high (> or =100 transplantations), medium (50 to 99
      transplantations), and low (<50 transplantations). SETTING: Transplantation
      centers in the United States. PATIENTS: 20 075 transplant recipients between 27
      February 2002 and 30 April 2006. MEASUREMENTS: MELD scores and waiting times of
      liver transplant recipients. RESULTS: Transplant recipients at high-volume
      centers had lower MELD scores (35.1% with MELD scores < or =18 vs. 22.7% and
      27.0% at medium- and low-volume centers, respectively; P < 0.001), and the median
      MELD score was 22 compared with 24 at both medium- and low-volume centers.
      Despite having lower MELD scores, recipients at high-volume centers also
      experienced shorter waiting times (median waiting time, 69 days vs. 98 days and
      94 days at medium-and low-volume centers, respectively; P < 0.001). LIMITATIONS:
      The definition of transplantation center volume was subjective. The recent
      implementation of MELD precluded analysis of differences in long-term outcomes
      related to waiting time or center volume. CONCLUSIONS: The MELD scores and
      waiting time of liver transplant recipients differed by transplantation center
      volume. High-volume centers have shorter waiting times and perform more
      transplantations for less sick patients. The reasons for these differences are
      unclear but warrant further investigation.

PMID- 17502633
TI  - Narrative review: the pathophysiology of fibromyalgia.
AB  - Primary fibromyalgia is a common yet poorly understood syndrome characterized by
      diffuse chronic pain accompanied by other somatic symptoms, including poor sleep,
      fatigue, and stiffness, in the absence of disease. Fibromyalgia does not have a
      distinct cause or pathology. Nevertheless, in the past decade, the study of
      chronic pain has yielded new insights into the pathophysiology of fibromyalgia
      and related chronic pain disorders. Accruing evidence shows that patients with
      fibromyalgia experience pain differently from the general population because of
      dysfunctional pain processing in the central nervous system. Aberrant pain
      processing, which can result in chronic pain and associated symptoms, may be the
      result of several interplaying mechanisms, including central sensitization,
      blunting of inhibitory pain pathways, alterations in neurotransmitters, and
      psychiatric comorbid conditions. This review provides an overview of the
      mechanisms currently thought to be partly responsible for the chronic diffuse
      pain typical of fibromyalgia.

PMID- 17502632
TI  - Pharmacist intervention to improve medication adherence in heart failure: a
      randomized trial.
AB  - BACKGROUND: Patients with heart failure who take several prescription medications
      sometimes have poor adherence to their treatment regimens. Few interventions
      designed to improve adherence to therapy have been rigorously tested. OBJECTIVE:
      To determine whether a pharmacist intervention improves medication adherence and
      health outcomes compared with usual care for low-income patients with heart
      failure. DESIGN: Randomized, controlled trial conducted from February 2001 to
      June 2004. SETTING: University-affiliated, inner-city, ambulatory care practice.
      PATIENTS: 314 low-income patients 50 years of age or older with heart failure
      confirmed by their primary care physician. INTERVENTION: Patients were randomly
      assigned to intervention (39% [n = 122]) or usual care (61% [n = 192]) groups and
      were followed for 12 months. A pharmacist provided a 9-month multilevel
      intervention, with a 3-month poststudy phase. An interdisciplinary team of
      investigators designed the intervention to support medication management by
      patients who have low health literacy and limited resources. MEASUREMENTS:
      Primary outcomes were adherence, as measured by using electronic prescription
      monitors, and exacerbations requiring emergency department care or hospital
      admission. Secondary outcomes included health-related quality of life, patient
      satisfaction with pharmacy services, and total direct costs. RESULTS: During the
      9-month intervention period, medication adherence was 67.9% and 78.8% in the
      usual care and intervention groups, respectively (difference, 10.9 percentage
      points [95% CI, 5.0 to 16.7 percentage points]). However, these salutary effects
      dissipated in the 3-month postintervention follow-up period, in which adherence
      was 66.7% and 70.6%, respectively (difference, 3.9 percentage points [CI, -5.9 to
      6.5 percentage points]). Medications were taken on schedule 47.2% of the time in
      the usual care group and 53.1% of the time in the intervention group (difference,
      5.9 percentage points [CI, 0.4 to 11.5 percentage points]), but this effect also
      dissipated at the end of the intervention (48.9% vs. 48.6%, respectively;
      difference, 0.3 percentage point [CI, -5.9 to 6.5 percentage points]). Emergency
      department visits and hospital admissions were 19.4% less (incidence rate ratio,
      0.82 [CI, 0.73 to 0.93]) and annual direct health care costs were lower ($-2960
      [CI, $-7603 to $1338]) in the intervention group. LIMITATIONS: Because electronic
      monitors were used to ascertain adherence, patients were not permitted to use
      medication container adherence aids. The intervention involved 1 pharmacist and a
      single study site that served a large, indigent, inner-city population of
      patients. Because the intervention had several components, intervention effects
      could not be attributed to a single component. CONCLUSIONS: A pharmacist
      intervention for outpatients with heart failure can improve adherence to
      cardiovascular medications and decrease health care use and costs, but the
      benefit probably requires constant intervention because the effect dissipates
      when the intervention ceases. ClinicalTrials.gov registration number:
      NCT00388622.

PMID- 17502634
TI  - Systematic review: repair of unruptured abdominal aortic aneurysm.
AB  - BACKGROUND: Recent recommendations to screen for abdominal aortic aneurysm (AAA)
      in high-risk populations and the rapidly increasing use of endovascular repair
      have led to increased interest in evaluating the effectiveness of treatment
      options for patients with AAA. PURPOSE: To compare the effectiveness of treatment
      options, including active surveillance, open repair, and endovascular repair, for
      unruptured AAAs. DATA SOURCES: The authors searched MEDLINE, the Cochrane
      Library, and www.ClinicalTrials.gov through December 2006 with no language
      restrictions, searched reference lists, and queried experts and study authors.
      STUDY SELECTION: Randomized trials that compared open or endovascular AAA repair
      with another treatment strategy and published clinical outcomes. DATA EXTRACTION:
      Data were extracted onto standardized, piloted forms and were confirmed. DATA
      SYNTHESIS: Two trials compared open repair with surveillance for small AAAs (n =
      2226). Repair did not improve all-cause mortality (relative risk, 1.01 [95% CI,
      0.77 to 1.32]) or AAA-related mortality (relative risk, 0.78 [CI, 0.56 to 1.10]).
      Four trials compared open repair with endovascular repair (n = 1532).
      Endovascular repair reduced 30-day mortality (relative risk, 0.33 [CI, 0.17 to
      0.64]) but not mid-term (up to 4 years) mortality (relative risk, 0.95 [CI, 0.76
      to 1.19]). One trial compared endovascular repair with observation in 338
      patients who were unfit for open repair. Endovascular repair did not reduce all
      cause mortality or AAA-related mortality, but high crossover and procedural
      mortality rates complicate interpretation of results. LIMITATIONS: Few trials
      have been published. Those published were of small to moderate size and were not
      U.S. trials of endovascular repair. CONCLUSIONS: Repairing AAAs smaller than 5.5
      cm has not been shown to improve survival. Endovascular repair is associated with
      lower operative mortality than open repair, similar mid-term mortality, and
      unknown long-term mortality and has not been shown to improve survival in
      patients unfit for open repair. Long-term trial data comparing endovascular
      repair with open repair are needed, as is another trial comparing endovascular
      repair with observation in high-risk patients.

PMID- 17502635
TI  - Pharmaceutical marketing research and the prescribing physician.
AB  - Surveillance of physicians' prescribing patterns and the accumulation and sale of
      these data for pharmaceutical marketing are currently the subjects of legislation
      in several states and action by state and national medical associations. Contrary
      to common perception, the growth of the health care information organization
      industry has not been limited to the past decade but has been building slowly
      over the past 50 years, beginning in the 1940s when growth in the prescription
      drug market fueled industry interest in understanding and influencing prescribing
      patterns. The development of this surveillance system was not simply imposed on
      the medical profession by the pharmaceutical industry but was developed through
      the interactions of pharmaceutical salesmen, pharmaceutical marketers, academic
      researchers, individual physicians, and physician organizations. Examination of
      the role of physicians and physician organizations in the development of
      prescriber profiling is directly relevant to the contemporary policy debate
      surrounding this issue.

PMID- 17502636
TI  - Evidence-based screening and management of abdominal aortic aneurysm.

PMID- 17502637
TI  - Prescriber profiling: time to call it quits.

PMID- 17502638
TI  - A family affair.

PMID- 17502639
TI  - Dr. Wohl's Violin: a family doctor's last act of kindness.

PMID- 17502640
TI  - A philosophical approach to diagnostic test evaluation.

PMID- 17502641
TI  - Life expectancy and colorectal cancer screening.

PMID- 17502642
TI  - Institutional review board review of multicenter studies.

PMID- 17502643
TI  - The evolving story of "conditioning" to protect against acute myocardial
      ischaemia-reperfusion injury.

PMID- 17502644
TI  - Asynchronic and hypokinetic movement of the left ventricular posterior wall due
      to preexcitation syndrome.

PMID- 17502645
TI  - Is public access to surgeon-specific data affecting practice adversely?

PMID- 17502646
TI  - Post myocardial infarction left ventricular free wall rupture diagnosed by
      multidetector computed tomography.

PMID- 17502647
TI  - Preventing contrast nephropathy in catheter laboratory.

PMID- 17502648
TI  - Measurement and prevention of myocardial injury during percutaneous coronary
      intervention.

PMID- 17502650
TI  - Isolated "superdominant" single coronary artery: a particularly rare coronary
      anomaly.

PMID- 17502651
TI  - Metastatic squamous cell carcinoma causing right ventricular outflow tract
      obstruction.

PMID- 17502652
TI  - Evidence that pharmacological strategies lack efficacy for the prevention of
      sudden death in hypertrophic cardiomyopathy.
AB  - OBJECTIVE: To determine the efficacy of pharmacological treatment in the
      prevention of sudden cardiac death in hypertrophic cardiomyopathy (HCM). DESIGN:
      Clinical outcome was assessed retrospectively in 293 patients with HCM, including
      173 who were taking cardioactive medications. SETTING: Department of Cardiology,
      University of Padua, Padua, Italy; a tertiary HCM Centre. INTERVENTIONS: Medical
      treatment with beta blockers, verapamil, sotalol and amiodarone. MAIN OUTCOME
      MEASURE: HCM-related sudden cardiac death. RESULTS: 17 of 173 (10%) patients died
      suddenly or had aborted cardiac arrest, while being treated continuously with
      drugs having antiarrhythmic properties, over a period of 62 (56) months. Sudden
      death occurred in 20% of patients administered amiodarone (6/30), 9% each of
      patients taking verapamil (4/46) or beta blockers (7/76), and 0% of those taking
      sotalol (0/21). Patients taking cardioactive drugs (n = 173) and those without
      pharmaceutical therapy (n = 120) did not differ with respect to sudden death
      mortality. CONCLUSION: Medical treatment is not absolutely protective against the
      risk of sudden death in HCM. The present data inferentially support the use of
      the implantable defibrillator as the primary treatment choice for prevention of
      sudden death in high-risk patients with HCM.

PMID- 17502653
TI  - The "winking" coronary sinus.

PMID- 17502654
TI  - Evolving pneumopericardium.

PMID- 17502655
TI  - Featured correspondence. Comment on editorial by Ashrafian and Bogle.

PMID- 17502656
TI  - Antimicrobial prophylaxis for endocarditis: emotion or science?

PMID- 17502657
TI  - Severe intimal hyperplasia after sirolimus eluting stent deployment: evaluation
      by optical coherence tomography.

PMID- 17502658
TI  - Marfan syndrome: an update of genetics, medical and surgical management.

PMID- 17502659
TI  - Post mortem examinations after cardiac surgery.

PMID- 17502660
TI  - Stress testing in valve disease.

PMID- 17502661
TI  - Defects in coding joint formation in vivo in developing ATM-deficient B and T
      lymphocytes.
AB  - Ataxia-telangiectasia mutated (ATM)-deficient lymphocytes exhibit defects in
      coding joint formation during V(D)J recombination in vitro. Similar defects in
      vivo should affect both T and B cell development, yet the lymphoid phenotypes of
      ATM deficiency are more pronounced in the T cell compartment. In this regard, ATM
      deficient mice exhibit a preferential T lymphopenia and have an increased
      incidence of nontransformed and transformed T cells with T cell receptor
      alpha/delta locus translocations. We demonstrate that there is an increase in the
      accumulation of unrepaired coding ends during different steps of antigen receptor
      gene assembly at both the immunoglobulin and T cell receptor loci in developing
      ATM-deficient B and T lymphocytes. Furthermore, we show that the frequency of ATM
      deficient alphabeta T cells with translocations involving the T cell receptor
      alpha/delta locus is directly related to the number of T cell receptor alpha
      rearrangements that these cells can make during development. Collectively, these
      findings demonstrate that ATM deficiency leads to broad defects in coding joint
      formation in developing B and T lymphocytes in vivo, and they provide a potential
      molecular explanation as to why the developmental impact of these defects could
      be more pronounced in the T cell compartment.

PMID- 17502662
TI  - Type I interferons produced by hematopoietic cells protect mice against lethal
      infection by mammalian reovirus.
AB  - We defined the function of type I interferons (IFNs) in defense against reovirus
      strain type 1 Lang (T1L), which is a double-stranded RNA virus that infects
      Peyer's patches (PPs) after peroral inoculation of mice. T1L induced expression
      of mRNA for IFN-alpha, IFN-beta, and Mx-1 in PPs and caused localized intestinal
      infection that was cleared in 10 d. In contrast, T1L produced fatal systemic
      infection in IFNalphaR1 knockout (KO) mice with extensive cell loss in lymphoid
      tissues and necrosis of the intestinal mucosa. Studies of bone-marrow chimeric
      mice indicated an essential role for hematopoietic cells in IFN-dependent viral
      clearance. Dendritic cells (DCs), including conventional DCs (cDCs), were the
      major source of type I IFNs in PPs of reovirus-infected mice, whereas all cell
      types expressed the antiviral protein Mx-1. Neither NK cells nor signaling via
      Toll-like receptor 3 or MyD88 were essential for viral clearance. These data
      demonstrate a requirement for type I IFNs in the control of an intestinal viral
      infection and indicate that cDCs are a significant source of type I IFN
      production in vivo. Therefore, innate immunity in PPs is an essential component
      of host defense that limits systemic spread of pathogens that infect the
      intestinal mucosa.

PMID- 17502663
TI  - Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated
      suppression.
AB  - Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset
      of T cells, which are crucial for the maintenance of peripheral tolerance by
      controlling potentially autoreactive T cells. However, the underlying molecular
      mechanisms of this strictly cell contact-dependent process are still elusive.
      Here we show that naturally occurring T reg cells harbor high levels of cyclic
      adenosine monophosphate (cAMP). This second messenger is known to be a potent
      inhibitor of proliferation and interleukin 2 synthesis in T cells. Upon
      coactivation with naturally occurring T reg cells the cAMP content of responder T
      cells is also strongly increased. Furthermore, we demonstrate that naturally
      occurring T reg cells and conventional T cells communicate via cell contact
      dependent gap junction formation. The suppressive activity of naturally occurring
      T reg cells is abolished by a cAMP antagonist as well as by a gap junction
      inhibitor, which blocks the cell contact-dependent transfer of cAMP to responder
      T cells. Accordingly, our results suggest that cAMP is crucial for naturally
      occurring T reg cell-mediated suppression and traverses membranes via gap
      junctions. Hence, naturally occurring T reg cells unexpectedly may control the
      immune regulatory network by a well-known mechanism based on the intercellular
      transport of cAMP via gap junctions.

PMID- 17502664
TI  - RANK signals from CD4(+)3(-) inducer cells regulate development of Aire
      expressing epithelial cells in the thymic medulla.
AB  - Aire-expressing medullary thymic epithelial cells (mTECs) play a key role in
      preventing autoimmunity by expressing tissue-restricted antigens to help purge
      the emerging T cell receptor repertoire of self-reactive specificities. Here we
      demonstrate a novel role for a CD4(+)3(-) inducer cell population, previously
      linked to development of organized secondary lymphoid structures and maintenance
      of T cell memory in the functional regulation of Aire-mediated promiscuous gene
      expression in the thymus. CD4(+)3(-) cells are closely associated with mTECs in
      adult thymus, and in fetal thymus their appearance is temporally linked with the
      appearance of Aire(+) mTECs. We show that RANKL signals from this cell promote
      the maturation of RANK-expressing CD80(-)Aire(-) mTEC progenitors into
      CD80(+)Aire(+) mTECs, and that transplantation of RANK-deficient thymic stroma
      into immunodeficient hosts induces autoimmunity. Collectively, our data reveal
      cellular and molecular mechanisms leading to the generation of Aire(+) mTECs and
      highlight a previously unrecognized role for CD4(+)3(-)RANKL(+) inducer cells in
      intrathymic self-tolerance.

PMID- 17502665
TI  - Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells
      mediates immune suppression.
AB  - The study of T regulatory cells (T reg cells) has been limited by the lack of
      specific surface markers and an inability to define mechanisms of suppression. We
      show that the expression of CD39/ENTPD1 in concert with CD73/ecto-5'-nucleotidase
      distinguishes CD4(+)/CD25(+)/Foxp3(+) T reg cells from other T cells. These
      ectoenzymes generate pericellular adenosine from extracellular nucleotides. The
      coordinated expression of CD39/CD73 on T reg cells and the adenosine A2A receptor
      on activated T effector cells generates immunosuppressive loops, indicating roles
      in the inhibitory function of T reg cells. Consequently, T reg cells from Cd39
      null mice show impaired suppressive properties in vitro and fail to block
      allograft rejection in vivo. We conclude that CD39 and CD73 are surface markers
      of T reg cells that impart a specific biochemical signature characterized by
      adenosine generation that has functional relevance for cellular immunoregulation.

PMID- 17502667
TI  - Viruses and glycosylation: an overview.
AB  - Although many virus proteins are glycosylated, the pattern of glycosylation that
      is exhibited can be highly variable, and it is largely dependent on how a
      specific virus protein is processed by the host cell during infection. However,
      irrespective of their glycosylation pattern, many virus glycoproteins have been
      found to play essential roles during the virus replication cycle. Consequently,
      it is therefore becoming necessary to understand the effect that the attached
      glycans have on the function of different virus glycoproteins. As a first step
      towards understanding how glycans can influence the activity of a specific
      glycoprotein, we need to both establish the mechanism of glycosylation, and
      determine the nature of the attached glycans. This chapter provides an overview
      of some of the different ways in which viruses proteins are glycosylated, and
      highlights some of the generic techniques by which they can be examined.

PMID- 17502666
TI  - Selective blockade of the inhibitory Fcgamma receptor (FcgammaRIIB) in human
      dendritic cells and monocytes induces a type I interferon response program.
AB  - The ability of dendritic cells (DCs) to activate immunity is linked to their
      maturation status. In prior studies, we have shown that selective antibody
      mediated blockade of inhibitory FcgammaRIIB receptor on human DCs in the presence
      of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced
      immunity to antibody-coated tumor cells. We show that Fcgamma receptor (FcgammaR)
      mediated activation of human monocytes and monocyte-derived DCs is associated
      with a distinct gene expression pattern, including several inflammation
      associated chemokines, as well as type 1 interferon (IFN) response genes,
      including the activation of signal transducer and activator of transcription 1
      (STAT1). FcgammaR-mediated STAT1 activation is rapid and requires activating
      FcgammaRs. However, this IFN response is observed without a detectable increase
      in the expression of type I IFNs themselves or the need to add exogenous IFNs.
      Induction of IFN response genes plays an important role in FcgammaR-mediated
      effects on DCs, as suppression of STAT1 by RNA interference inhibited FcgammaR
      mediated DC maturation. These data suggest that the balance of
      activating/inhibitory FcgammaRs may regulate IFN signaling in myeloid cells.
      Manipulation of FcgammaR balance on DCs and monocytes may provide a novel
      approach to regulating IFN-mediated pathways in autoimmunity and human cancer.

PMID- 17502668
TI  - Interaction between respiratory syncytial virus and glycosaminoglycans, including
      heparan sulfate.
AB  - Glycosaminoglycans (GAGs), including heparan sulfate (HS), are expressed on the
      surface of nearly all cells, linked to transmembrane proteins. These GAGs are
      sulfated to varying extents, lending a negative charge, and are used by a large
      number of viruses to initiate infection of immortalized cell lines. Here we
      describe the rationale and methods for analyzing GAG usage by one such virus,
      respiratory syncytial virus (RSV). The protocols presented allow the
      determination of which GAG(s) is employed by the virus, which GAG modification(s)
      is important, and whether the important GAG is on the cell or on the virus. We
      also discuss the finding that many viruses are selected for GAG usage during
      passage in culture and present a method for rapidly determining whether GAG usage
      is characteristic of a wild virus or is limited to laboratory-adapted virus.

PMID- 17502669
TI  - Expression of the severe acute respiratory syndrome coronavirus 3a protein and
      the assembly of coronavirus-like particles in the baculovirus expression system.
AB  - The Bac-to-Bac Baculovirus expression system was used to generate a recombinant
      baculovirus capable of expressing the severe acute respiratory syndrome (SARS)
      coronavirus (CoV) 3a protein. Using the same expression system, two structural
      proteins, membrane (M) and envelope (E), were co-expressed to form SARS-CoV virus
      like particles (VLPs) within an insect cell. Expression of viral proteins was
      confirmed by Western blot analysis and the formation of VLPs was studied by
      transmission electron microscopy.

PMID- 17502671
TI  - Functional analysis of the N-linked glycans within the fusion protein of
      respiratory syncytial virus.
AB  - The respiratory syncytial virus fusion (F) protein is initially expressed as a
      single polypeptide chain (F0). The F0 subsequently undergoes posttranslational
      cleavage-by-cell protease activity to produce the F1 and F2 subunits. Each of the
      two subunits within the mature F protein is modified by the addition of N-linked
      glycans. The individual N-linked glycans on the F protein were selectively
      removed by using site-directed mutagenesis to mutate the individual glycan
      acceptor sites. In this way the role of these individual glycans in targeting of
      the F protein to the cell surface, and on the ability of the F protein to induce
      membrane fusion, was examined.

PMID- 17502670
TI  - The C type lectins DC-SIGN and L-SIGN: receptors for viral glycoproteins.
AB  - DC-SIGN and L-SIGN are C-type lectins that recognize carbohydrate structures
      present on viral glycoproteins and function as attachment factors for several
      enveloped viruses. DC-SIGN and L-SIGN enhance viral entry and facilitate
      infection of cells that express the cognate entry receptor (cis-infection). They
      are also able to capture viruses and transfer viral infections to other target
      cells (trans-infection). In this chapter, we will give an overview of protocols
      used to produce soluble viral glycoproteins at high levels and to study the
      molecular basis of viruses/DC-SIGN and L-SIGN binding and internalization. We
      will also describe techniques to investigate the molecular mechanisms by which DC
      SIGN or L-SIGN spread viral infections.

PMID- 17502672
TI  - Expression and purification of viral glycoproteins using recombinant vaccinia
      viruses for functional and structural studies.
AB  - Methods for generating recombinant vaccinia viruses for the expression of foreign
      viral glycoproteins in mammalian cell lines and the purification of expressed
      viral glycoproteins are described. These methods are based on many years of
      experience with the influenza hemagglutinin glycoprotein (HA). However, they are
      applicable for studies on other viral glycoproteins, and with slight
      modifications, could be useful for cellular proteins as well.

PMID- 17502673
TI  - The use of two-dimensional SDS-PAGE to analyze the glycan heterogeneity of the
      respiratory syncytial virus fusion protein.
AB  - The respiratory syncytial virus (RSV) fusion (F) protein is synthesized as an
      inactive precursor (F0), which subsequently undergoes post-translational cleavage
      to give the disulphide bond-linked F1 and F2 subunits. The methodology detailing
      the use of two-dimensional electrophoresis, endoglycosidases, and alpha
      mannosidase inhibitors, as applied to investigating F protein glycan maturation,
      is given. Examples are used to show how this methodology was used to provide
      evidence for glycan heterogeneity within the mature F protein.

PMID- 17502674
TI  - The use of monoclonal antibodies and lectins to identify changes in viral
      glycoproteins that are influenced by glycosylation: the case of human respiratory
      syncytial virus attachment (G) glycoprotein.
AB  - The influence of viral envelope glycans is often overlooked, but one should bear
      in mind that variable glycosylation may affect the properties of viral envelope
      glycoproteins and potentially alter the course of an infection. Hence, there is a
      need for simple methods that can be use to identify changes in the glycosylation
      pattern of viral glycoproteins in a large number of samples. We describe here
      methods for the analysis of cell-line specific changes in glycosylation of the
      respiratory syncytial virus (RSV) attachment glycoprotein (G), which involve the
      use of lectins and anti-carbohydrate antibodies. Given the role of the G
      glycoprotein in RSV antigenicity, we also describe procedures based on Western
      blotting to determine the effect of G protein glycosylation changes on reactivity
      with human sera. We found that glycosylation of the C-terminal domain of the G
      protein reduces reactivity with human sera, indicating that variable
      glycosylation may contribute to evasion of the humoral immune response by RSV.

PMID- 17502675
TI  - Expression, glycosylation, and modification of the spike (S) glycoprotein of SARS
      CoV.
AB  - The spike (S) glycoprotein of coronaviruses is known to be essential in the
      binding of the virus to the host cell at the advent of the infection process. To
      study the maturation pathway of the S glycoprotein of the severe acute
      respiratory syndrome (SARS)-coronavirus (CoV) within the host cell, a T7/vaccinia
      virus-based expression system coupled to immunoprecipitation with anti-S
      antibodies was used to test and analyze different forms of the S glycoprotein.
      The state of maturity of the S glycoprotein can be deduced from its sensitivity
      to hydrolysis by endoglycosidase H (EndoH) or N-glycosidase F (N-Gly F). A fully
      matured S glycoprotein will be modified with complex oligosaccharides which makes
      it resistant to cleavage by EndoH but not by N-Gly F. By exploiting this
      characteristic, it is then possible to determine which forms of the
      immunoprecipitated S protein are properly processed by the host cell. With this
      system, many different constructs of the S glycoprotein can be analyzed in
      parallel thus providing another method by which to study the functional domains
      of S involved in membrane fusion event that occurs during viral infection.

PMID- 17502676
TI  - Analysis of glycoproteins of viruses in the family Bunyaviridae.
AB  - The membrane glycoproteins (Gn and Gc) of viruses in the family Bunyaviridae form
      projections on the virion envelope and are involved in virus entry and eliciting
      protective immunity. The glycoproteins are modified by N-linked glycosylation and
      accumulate in the Golgi complex where virions mature and bud. In this chapter, we
      describe the methods that have been used in our laboratory for the study of the
      glycoproteins of Bunyamwera virus, the prototype of the family. The protocols
      cover the expression of viral glycoproteins, examination of intracellular
      localization by immnunofluorescent confocal microscopy, radiolabeling,
      immunoprecipitation, and SDS-PAGE analysis of the proteins, and the improved
      reverse genetic system to rescue recombinant viruses that contain mutations at N
      linked glycosylation sites.

PMID- 17502677
TI  - Secretion of the respiratory syncytial virus fusion protein from insect cells
      using the baculovirus expression system.
AB  - Sequences derived from the respiratory syncytial virus (RSV) fusion (F) protein
      were expressed in insect cells as recombinant glutathione-S-transferase (GST)
      tagged proteins. The sequence covering the F2 subunit (GST-F2), and a truncated
      form of the F protein in which the transmembrane domain was removed (GST-F2/F1),
      were cloned into the baculovirus pAcSecG2T secretory vector. These virus
      sequences also had the endogenous virus signal sequence removed and replaced with
      a signal sequence derived from the baculovirus gp67 glycoprotein, which was
      present in pAcSecG2T. The recombinant RSV glycoproteins were successfully
      detected in expressing cells by immunofluorescence assay and in the tissue
      culture medium by western blot analysis. The secreted recombinant GST-F2/F1
      protein was further analysed using glycosidases. Our results showed that the GST
      F2/F1 protein were sensitive to peptide:N-glycosidase F (PNGase F) treatment, but
      not to Endoglycosidase H (EndoH) treatment. This indicates that the secreted
      recombinant proteins were modified by the addition of mature N-linked glycan
      chains.

PMID- 17502678
TI  - Characterization of the dengue virus envelope glycoprotein expressed in Pichia
      pastoris.
AB  - The full-length and truncated forms of recombinant envelope (E) glycoprotein from
      Dengue virus type 1, Singapore strain S275/90 were expressed in the yeast, Pichia
      pastoris, using a secretory vector. A truncated form of the E protein in which
      the transmembrane domain was deleted was secreted successfully into the culture
      medium. The E protein was also co-expressed with C and prM proteins using a non
      secretory yeast vector. The co-expression of C, prM and E proteins resulted in
      the spontaneous formation of virus-like particles (VLPs), which were confirmed by
      sucrose gradient analysis and transmission electron microscopy. Furthermore, the
      VLPs were used to immunise rabbits, and shown to be immunogenic by
      immunofluorescence staining of dengue virus-infected Vero cells. The yeast
      expressed E protein was treated with PNGase F, which showed that although the
      protein was modified by the addition of N-linked glycans, the recombinant
      expressed E protein was not hyperglycosylated.

PMID- 17502679
TI  - Cloning, expression, and functional analysis of patient-derived hepatitis C virus
      glycoproteins.
AB  - Hepatitis C virus (HCV) infection is a major cause of severe chronic liver
      disease including cirrhosis and hepatocellular carcinoma. HCV has been classified
      into six major genotypes that exhibit extensive genetic variability, particularly
      in the envelope glycoproteins E1 and E2. Knowledge of genotypic and quasispecies
      variation on viral glycoprotein properties is important in understanding the
      structure-function relationship of the proteins. Through their perceived role as
      components of the virion and mediators of virus attachment and entry, HCV
      glycoproteins are primary targets for the development of antiviral agents. In
      this chapter, we describe methods optimized to extract E1E2-encoding sequences of
      all the major genotypes from HCV-infected patient sera, and their amplification,
      cloning, expression, and biochemical characterization. Furthermore, we describe a
      method to generate retroviral nucleocapsid pseudotyped with HCV E1E2 of diverse
      genotypes (HCVpp) whereby infectivity of the retroviral particle is conferred by
      HCV glycoproteins. Finally, we show how the HCVpp can be used in an infection
      assay to determine the viral glycoprotein function at the level of the host
      pathogen interface and subsequent events leading to virus infection.

PMID- 17502681
TI  - [The Icelandic Surgents Society 50 years].

PMID- 17502680
TI  - [In times of diabetes].

PMID- 17502682
TI  - [Prevalence of type 2 diabetes mellitus in Iceland 1967-2002].
AB  - BACKGROUND AND AIMS: The prevalence of type 2 diabetes (T2DM) is increasing at an
      alarming rate worldwide. The prevalence of T2DM in Iceland has been comparatively
      low. The aim of this study is to estimate the prevalence of T2DM in Iceland from
      1967-2002 using American Diabetic Association (ADA) '97 criteria and to assess
      the effect of employing three different diagnostic criteria: World Health
      Organization (WHO) '85, ADA'97, WHO'99. MATERIALS AND METHODS: This study is
      based on data from the Icelandic Heart Association (IHA), mostly from a
      representative random sample of the Icelandic population (The Reykjavik Study).
      The total population of this survey is 16393, 7852 males and 8541 females, aged
      45-64. The study period was divided into five equal size cross-sectional periods,
      each about 6 years. The prevalence of T2DM was computed for every period.
      RESULTS: The age-standardized prevalence (95% CI) of T2DM in males, computed
      according to ADA'97 criteria has in a 30 year period risen from 3.3% (2.6-4.0) to
      4.9% (3.5-5.3) which is an increase of 48%. In females the prevalence rose from
      1.9% (1.4-2.4) to 2.9% (1.9-3.9) in the same period, a 53% increase. The Ratio of
      unknown T2DM is 0.66. Prevalence of T2DM in obese males and females is 10.6% (95%
      CI: 8.6-12.6) and 7.1% (95% CI: 5.5-8.7) respectively. CONCLUSION: The prevalence
      of T2DM is now increasing in Iceland as in the rest of the world although the
      increase has taken place somewhat later than elsewhere. The prevalence of T2DM is
      however still relatively low when compared to other western countries. Early
      detection of T2DM is of importance and screening should be used according to
      clinical guidelines. The current increase in T2DM is most likely due to
      increasing obesity.

PMID- 17502683
TI  - [Comparison of video-assisted thoracoscopic surgery and limited axillary
      thoracotomy for spontaneous pneumothorax].
AB  - INTRODUCTION: Historically, surgery for SP has been performed with open
      thoracotomy. Today video-assisted thoracoscopic surgery (VATS) has replaced open
      surgery for SP in most centers. Long-term results (i.e. recurrent pneumothorax)
      following VATS have been debated. In Iceland surgery for SP has been performed
      with both VATS and limited axillary thoracotomy (LAT). The aim of this study was
      to compare these two approaches, especially reoperations for prolonged airleakage
      and late recurrences. MATERIAL AND METHODS: This is a retrospective non
      randomized study on all patients operated first time for SP at our institution
      between 1991-2005. Out of 210 patients that underwent 234 procedures (160 males,
      mean age 29 yrs.), 200 had primary SP (95%) and 10 secondary SP. The cases were
      divided into two groups; 134 VATS procedures and 100 thoracotomies (LAT). Three
      surgeons performed a LAT and four performed VATS. RESULTS: Wedge resection was
      performed in all cases and mechanical pleurodesis was added in 25% of the VATS
      and 67% of the LAT cases. Median operation time was 20 minutes longer for VATS
      (p=0.006). Reoperations for late recurrent pneumothorax were 10 vs. 3 in the VATS
      and LAT group, and reoperations for persistent airleakage 3 vs. 0, respectively
      (p=0.03). Operative mortality within 30 days from surgery was 0%. Median hospital
      stay was one day longer after LAT. CONCLUSION: Reoperations following VATS for SP
      are more common compared to open thoracotomy, explained by a higher rate of both
      late recurrent pneumothoraces and prolonged early postoperative airleakage. Both
      approaches are safe and major complications are infrequent. Hospital stay is
      shorter after VATS, however, VATS takes longer and the higher reoperation rate is
      a shortcoming and is of concern.

PMID- 17502684
TI  - [Spontaneous pneumothorax: a review article].
AB  - Spontaneous pneumothorax is a relatively common disease primarily affecting young
      and otherwise healthy individuals. Chest pain and dyspnea are the most common
      presenting symptoms and in majority of cases only a chest X-ray is needed to
      confirm the diagnosis. The initial treatment usually consist of a chest tube
      drainage, however, persistent airleakage and recurrent pneumothorax are frequent,
      these patients often requiring surgery. Open thoracotomy was the most common
      surgical approach with wedge resection of the leaking part of the lung. Today,
      video-assisted thoracoscopic surgery has in most centers replaced open surgery
      for spontaneous pneumothorax. In this article the presentation, diagnosis and
      treatment of spontaneous pneumothorax, including different surgical strategies,
      are reviewed in an evidence-based approach.

PMID- 17502685
TI  - A mathematical model for the dissolution of non-occlusive blood clots in fast
      tangential blood flow.
AB  - Our aim was to study the effect of an axially directed blood plasma flow on the
      dissolution rate of cylindrical non-occlusive blood clots in an in vitro flow
      system and to derive a mathematical model for the process. The model was based on
      the hypothesis that clot dissolution dynamics is proportional not only to the
      biochemical proteolysis of fibrin but also to the power of the flowing blood
      plasma dissipated along the clot. The predicted rate of thrombolysis is then
      proportional to the square of the average blood plasma velocity for laminar flow
      and to the third power of the average velocity for turbulent flow. To verify the
      model, the time dependence of the clot cross-sectional area was measured by
      dynamic magnetic resonance microscopy during fast (turbulent) and slow (laminar)
      flow of plasma through an axially directed channel along the clot. The flowing
      plasma contained a magnetic resonance imaging contrast agent (Gd-DTPA) and a
      thrombolytic agent (recombinant tissue-type plasminogen activator). The
      experimental data fitted well to the model, and confirmed the predicted increase
      in the dissolution rate when blood flow changed from a laminar to a turbulent
      flow regime.

PMID- 17502686
TI  - The properties of gelatin-poly (gamma-glutamic acid) hydrogels as biological
      glues.
AB  - The influence of the molecular weight and the type of gelatin (A or B), as well
      as the molecular weight of poly (gamma-glutamic acid) (gamma-PGA), on the
      properties of gelatin/gamma-PGA mixed bioadhesives were studied. The gelation of
      the system was enhanced by a crosslinker, 1-(3-dimethylaminopropyl)-3
      (ethylcarbodiimide) hydrochloride (EDC). The gelation time of the bioadhesives
      was analyzed using rheological measurements. The results indicated that the type
      of gelatin was a critical factor in determining the gelation time of the
      biological glues. The mixed glues had greater bonding strength and smaller
      gelation times as the molecular weight of gamma-PGA or gelatin increased. The
      swelling ratio decreased and the denaturation temperature increased upon raising
      the EDC concentration, indicating a greater degree of crosslinking at higher EDC
      concentrations. The mixed glues crosslinked with various concentrations of EDC
      (1.7-2.5%) showed no cytotoxicity to fibroblasts. In addition, no significant
      inflammatory response was observed in the rat subcutaneous implantation. The
      bioadhesives based on gelatin/gamma-PGA remained at the site for 7 days while the
      fibrin glue had almost completely degraded. By choosing the appropriate gelatin
      type and higher molecular weight gamma-PGA in the mixtures, the gelatin/gamma-PGA
      biological glues could serve as soft tissue adhesives. Rheological
      characterization was essential in the evaluation of biological glues.

PMID- 17502687
TI  - Red blood cell aggregation quantitated via Myrenne aggregometer and yield shear
      stress.
AB  - Although the study of red blood cell (RBC) aggregation continues to be of basic
      science and clinical interest, aggregation standards for calibration do not
      exist, and most aggregation studies report data in terms of arbitrary units:
      quantitative comparisons between studies are thus essentially precluded. However,
      use of low shear viscometry plus the Casson equation provides a yield shear
      stress that has defined units and is known to reflect RBC aggregation. Employing
      human RBC-plasma suspensions exhibiting a wide range of aggregation, the present
      study examined relations between yield shear stress values and aggregation
      indices obtained using the Myrenne aggregometer: the latter approach uses a light
      transmission technique and provides an "M" index at stasis and an "M1" at very
      low shear. Our results for normal controls and for angina patients without
      coronary artery disease indicate highly significant correlations (p<0.001)
      between the yield stress and both M and M1. Thus, within the range of aggregation
      studied, these findings lend support to the rheological validity of the Myrenne
      approach; extension of our findings to intensely aggregating RBC suspensions may
      require additional validation studies.

PMID- 17502688
TI  - Changes in the integrin-mediated adhesion of human neutrophils in the cold and
      after rewarming.
AB  - Changes in the mechanical and adhesive properties of neutrophils may modify
      perfusion of the microcirculation in cooled tissue. We tested how integrin
      mediated adhesion of isolated human neutrophils was altered by cooling, or
      cooling and rewarming. First, adhesion was tested in a static assay. In the
      presence or absence of integrin-activating agents (formyl peptide, fMLP or
      Mn(++)), there were significant reductions in adhesion to immobilised albumin at
      10 degrees C or 0 degrees C compared to 37 degrees C, although a slight increase
      in adhesion was induced by fMLP or Mn(++) at 10 degrees C or 0 degrees C. If
      cells were cooled for 5 or 20 min at 10 degrees C and rewarmed (in the absence of
      activators) there was >100% increase in adhesion compared to cells held at 37
      degrees C. In a flow assay, neutrophils perfused over P-selectin at 37 degrees C
      formed rolling attachments, but if neutrophils were cooled to 10 degrees C and
      rewarmed for 1 or 5 min, there was transformation to stationary adhesion, which
      was reversed by antibody against CD18. After 20 minutes of rewarming, rolling was
      restored. Cooling and rewarming did not cause de novo expression of CD11b/CD18,
      and so appears to transiently activate constitutively-expressed integrin. Thus,
      integrin-mediated adhesion may be impaired in cold tissue but on return to normal
      temperature, neutrophils may transiently adhere locally or in remote vessels.

PMID- 17502689
TI  - Towards a reliable characterisation of the mechanical behaviour of brain tissue:
      The effects of post-mortem time and sample preparation.
AB  - Since the early seventies, the material properties of brain tissue have been
      studied using a variety of testing techniques. However, data reported in
      literature show large discrepancies even in the linear viscoelastic regime. In
      the current study, the effect of the sample preparation procedure and of post
      mortem time on the mechanical response of porcine brain tissue is examined.
      Samples from the thalamus region were prepared with different techniques and were
      tested for different loading histories. Each sample was tested in oscillatory
      shear tests (1% strain amplitude, 1-10 Hz frequencies) followed by sequences of
      5% strain loading-unloading cycles. The stress response to the loading-unloading
      cycles showed a clear dependency on post-mortem time, becoming more stiff with
      increasing time. This dependency was affected by the mechanical history induced
      by the preparation procedure.

PMID- 17502690
TI  - Evaluation of chondrocytes expression embedded in thermoresponsive poly(amino
      acid)s with sol-gel transition.
AB  - Poly(N-substituted alpha/beta-asparagine) was evaluated as a thermoresponsible
      and an injectable scaffold for cartilage regeneration. Solutions of this polymer
      are liquid state below 25 degrees C and nonfluid hydrogel above 35 degrees C,
      allowing an aqueous solution containing cells at room temperature to form a
      hydrogel with encapsulated cells at physiological body temperature. Chondrocytes
      were isolated from joint of 4-week-old Japanese white rabbits, dispersed within
      the thermoresponsive polymer solution and maintained for up to 72 hours in vitro.
      The polymer solutions demonstrated concentration-dependent inhibitory effect on
      chondrocytes multiplication. After the three-day cultivation, the survival rate
      of the chondrocytes fell into a 70~90% ranges among all the tested polymer
      concentrations. The morphology studies showed that there were some physical
      and/or chemical stress leading cells to necrosis and some extent apoptosis. Some
      physical and/or chemical stress may be applied, and over 70% of the chondrocytes
      could survive through the stress, suggesting that some phenotype could have been
      selected from the heterogeneous mixture of chondrocytes.

PMID- 17502691
TI  - Characterization of a poly-epsilon-caprolactone polymeric drug delivery device
      built by selective laser sintering.
AB  - Selective Laser Sintering (SLS), an established Rapid Prototyping (RP) process,
      is investigated for building controlled drug delivery devices (DDD). The drug and
      its matrix in a powder form were first mixed mechanically before being sintered
      on the SLS. Each cylindrical DDD is designed with a number of concentric rings
      separated from each other by a characteristic 'wall' created by the laser of the
      SLS. These rings act as diffusion obstacles to control the rate of release. Poly
      epsilon-caprolactone (PCL) was used as the matrix and Methylene Blue (MB) as the
      drug model. Samples were built, characterized and tested for homogeneity using
      Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and
      Fourier Transform Infrared Spectrophotometry (FTIR). Experimental results show
      that the matrices fabricated are not affected by sintering and the polymer and
      drug model are evenly distributed throughout the matrix. The initial burst effect
      has been reduced by the increase of the numbers of rings. The linear curve using
      the Higuchi equation confirmed that the DDD matrix release profile is by
      diffusion. These results show that the DDD matrix design has promising potential
      for application in controlled release drug delivery.

PMID- 17502692
TI  - Investigations on inducible nitric oxide synthase (iNOS) gene expression and SEM
      analysis during the interaction of a novel tissue adhesive with J774A.1 mouse
      macrophage cells.
AB  - A novel tissue adhesive consisting of human serum albumin (HSA) and tartaric acid
      derivative (TAD) was developed by us. Four different concentrations of TAD
      namely, 0.05 mmol, 0.1 mmol, 0.2 mmol and 0.3 mmol were mixed with 40%, 42% and
      44% HSA individually and were made in the form of disks. J774A.1 mouse macrophage
      cells were seeded on top of these disks. The disks were pre-treated with sterile
      water and Eagle's medium before every seeding. All the seeding was incubated from
      1 day to 3 days before making any investigations on it. SEM images were recorded
      and it was observed that these cells adhered to these materials very well. Nitric
      oxide activity was studied using nitrate/nitrite colorimetric assay method. It
      was observed that the total NO production is almost the same for 40% and 42% HSA
      for the respective concentrations of 0.05 mmol to 0.3 mmol TAD at all incubation
      times from 1 d to 3 d. On the other hand, the NO activity considerably decreases
      for 44% HSA at all concentrations from 0.05 to 0.3 mmol TAD. This trend is
      observed for all the three days of incubation. From the iNOS mRNA RT-PCR
      experiments, it was observed that no tendency of the gene expression of iNOS was
      significantly found and the expression level of this gene is not affected by the
      concentrations of both HSA and TAD. iNOS may be up-regulated by TAD in the early
      stage of culture (day 1) but no significant change was observed on day 2 and 3.
      On the whole 0.3 mmol TAD with 44% HSA could be considered as a challenging
      material as a tissue adhesive for use in the field of tissue engineering. Ours is
      the first report on iNOS gene expression on a tissue adhesive.

PMID- 17502693
TI  - Contact stresses in lumbar total disc arthroplasty.
AB  - Total disc arthroplasty is gaining in popularity as an alternative to spinal
      fusion. A total disc consists of articulating bearing surfaces with one made from
      a metal and the other made from either a metal or a polymer. The aim of this
      study was to determine the contact stresses in lumbar total disc arthroplasty
      devices. The total disc was modelled as a ball and socket joint and Hertzian
      contact theory was used to determine the maximum contact stresses. The effect of
      material combination and implant size on contact stress was investigated. For a
      typical disc arthroplasty with a ball radius of 14 mm, the contact stresses for
      metal against polymer and metal against metal material combinations were 3 to 6
      MPa and 63-130 MPa, respectively, and were below the fatigue strength of the
      materials.

PMID- 17502694
TI  - Oxygen plasma pre-treatment improves the wear properties of a diamond-like carbon
      film coated on UHMWPE and PMMA for biomaterials.
AB  - Diamond-like carbon (DLC) films were deposited on ultra-high molecular weight
      polyethylene (UHMWPE) and polymethylmethacrylate (PMMA) with oxygen plasma pre
      treatment using a radiofrequency plasma chemical vapour deposition method. A ball
      on-disc test was carried out to evaluate the wear properties of the DLC-coated
      UHMWPE and PMMA. After testing, the surface of the polymers was observed using an
      atomic force microscope and an optical microscope. The adhesive strength of the
      DLC films deposited on the polymers was measured using a scratch test. After the
      ball-on-disc test, many cracks were observed in the films on the surface of both
      the DLC-coated UHMWPE and PMMA without the oxygen plasma pre-treatment, whereas
      the DLC-coated UHMWPE and PMMA with oxygen plasma pre-treatment showed no cracks
      and good wear resistance. In the scratch test, the adhesion strength of the DLC
      film to the PMMA substrate increased from 42.5 mN to 101.3 mN with oxygen plasma
      pre-treatment.

PMID- 17502695
TI  - Detection of arterial disorders by spectral analysis techniques.
AB  - This paper intends to an integrated view of the spectral analysis techniques in
      the detection of arterial disorders. The paper includes illustrative information
      about feature extraction from signals recorded from arteries. Short-time Fourier
      transform (STFT) and wavelet transform (WT) were used for spectral analysis of
      ophthalmic arterial (OA) Doppler signals. Using these spectral analysis methods,
      the variations in the shape of the Doppler spectra as a function of time were
      presented in the form of sonograms in order to obtain medical information. These
      sonograms were then used to compare the applied methods in terms of their
      frequency resolution and the effects in determination of OA stenosis. The author
      suggest that the content of the paper will assist to the people in gaining a
      better understanding of the STFT and WT in the detection of arterial disorders.

PMID- 17502696
TI  - New artificial nerve conduits made with photocrosslinked hyaluronic acid for
      peripheral nerve regeneration.
AB  - For peripheral nerve regeneration, three-dimensional distribution and growth of
      cells within the porous scaffold are of clinical significance. We demonstrate
      that cultured rat Schwann cells and neurospheres grow in vitro on new artificial
      nerve conduits made with photocrosslinked hyaluronic acid (HA). HA tubular
      conduits have an inner diameter of 1.2 mm with porous nano-structure of 50
      microm. After 3 weeks of cultivation, HA conduits remained circular with a round
      lumen, and construct of cell-conduits maintained the size and shape of the
      original architecture of the tube. HA itself has the function to facilitate a
      pathway for cellular and axonal ingrowth during peripheral nerve regeneration.
      These findings provide the feasibility of using the HA conduits for better cell
      adhesion and differentiation, leading to axonal regeneration in peripheral nerve
      reconstruction.

PMID- 17502697
TI  - Haemorheological variables in Nigeria pulmonary tuberculosis patients undergoing
      therapy.
AB  - Haemorheological changes in response to therapy have not been fully determined in
      pulmonary tuberculosis patients living in developing countries. This study was
      aimed at monitoring haemorheological parameters in newly diagnosed pulmonary
      tuberculosis patients undergoing therapy. Haemorheological parameters were
      studied in 40 tuberculosis patients (17 males and 23 females, mean age 33.4+/-1.4
      years, range 23-45 years) undergoing treatment and 10 newly diagnosed patients (5
      males and 5 females mean age 33.0+/-2.1 years) along with 50 apparently healthy
      controls age and sex matched. There were significantly lower packed cell volume
      (PCV), platelet count (PC), and total white blood cell count (p<0.0001). Whole
      blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate
      (ESR), and plasma fibrinogen (PF) were significantly higher in pulmonary
      tuberculosis patients than controls (p<0.0001). The packed cell volume was
      significantly increased by the 8th week of therapy (p<0.01), there was a
      significant reduction in the erythrocyte sedimentation rate from the 4th week of
      therapy (p<0.0001). There was no significant change in blood viscosity by the 4th
      week of therapy (p>0.05), while the plasma fibrinogen showed significant
      reduction from the 4th week of therapy till 8th week of therapy (p<0.01 and
      p<0.0001 respectively). We conclude that thrombocytopaenia, stasis and
      hyperfibrinogenemia may predispose African PTB patients to bleeding and
      thrombotic disorders. Haemorheological parameters may be useful indices in
      assessing response to therapy and drug compliance in pulmonary tuberculosis
      patients living in developing countries.

PMID- 17502698
TI  - The direct thrombin inhibitor melagatran counteracts endotoxin-induced
      endothelial leukocyte adherence and microvascular leakage in the rat mesentery.
      Rationale for the treatment of inflammatory disorders beyond sepsis?
AB  - The activation of the coagulation system in the course of an inflammatory
      reaction impairs the function of the microcirculation. By means of intravital
      videomicroscopy the effect of the direct thrombin inhibitor melagatran on
      endotoxin-induced microvascular permeability and leukocyte adhesion to
      microvascular endothelium of rat mesentery was evaluated. Secondly, plasma
      concentrations of melagatran or interleukin-6 in response to endotoxin or after
      treatment with melagatran respectively, were determined. Male Sprague-Dawley rats
      (300-400 g bw) were infused with 0.5 mg/kg lipopolysaccharide (LPS) (E. coli
      O55:B5) over 80 minutes. Vascular leakage was detected with FITC-marked rat serum
      albumin by fluorescence microscopy and evaluated by grey value analysis with a
      computer assisted image processing system. Light microscopy was used to evaluate
      the adherence of leukocytes to the vessel wall. Two treated groups received
      either 0.3 or 0.6 mg/kg bw melagatran iv in addition to LPS-infusion. The
      observation period was 3 hours after the beginning of LPS infusion. Groups of
      animals not infused with LPS or solely treated with melagatran (0.3 or 0.6 mg/kg)
      served as controls. Infusion of LPS led to a significant increase of
      microvascular permeability, leukocyte adherence and thrombin-antithrombin complex
      plasma concentration compared to unstimulated controls. These effects were
      significantly reduced by melagatran at both dosage levels. Elevated plasma
      concentrations of melagatran were observed in animals infused with endotoxin and
      higher plasma levels of interleukin-6 were found in endotoxemic animals treated
      with melagatran. The results indicate that thrombin is one of the most important
      clotting enzymes involved in inflammatory microvascular disturbance. Moreover, it
      should be clarified whether direct thrombin inhibitors themselves play a role
      within the immune response to endotoxin.

PMID- 17502699
TI  - Red blood cell deformability in patients with sepsis: a marker for prognosis and
      monitoring of severity.
AB  - Sepsis in different states of severity (sepsis, severe sepsis, septic shock and
      adult respiratory distress syndrome (ARDS)) is associated with microcirculatory
      blood flow abnormalities leading to decreased red blood cell's (RBC's)
      deformability, impaired oxygen delivery to tissues and organs failure. The main
      goal of the present study, was to first determine the values of RBC's
      deformability, in the course of patients treated in an Intensive Care Unit (ICU)
      for basically sepsis and then deteriorated states and secondly to establish the
      prognostic efficiency of the test. For this purpose a filtration method and the
      hemorheometer, was used to determine experimentally the RBC's deformability, by
      measuring the RBC's Index of Rigidity (IR). Our results indicated that the IR was
      significantly increased in all patient groups and it was found to be
      approximately 51% higher in patients with sepsis, 229% in patients with severe
      sepsis, 1285% in patients with septic shock and 923% in patients with ARDS than
      in the healthy donors. The relationships between IR and Simplified Acute
      Physiology Score II (SAPS) and IR and Projected Mortality (PM) were found to be
      IR = 2.0237(SAPS) - 58.807 (r=0.731) and IR = 1.0671(PM) - 5.9829 (r=0.726)
      respectively. Our findings imply a significant impairment of the membrane's
      deformability possibly due to changes in its structure. It seems that the RBC's
      deformability is a useful mechanical parameter to estimate the prognosis and
      monitor patients suffering from different severity levels of sepsis.

PMID- 17502700
TI  - The influence of a multifunctional, polymeric biomaterial on the concentration of
      acute phase proteins in an animal model.
AB  - The concentrations of the acute phase proteins alpha1-Acid Glycoprotein (AAG) and
      haptoglobin were determined in Sprague-Dawley-rats after implantation of a novel
      biodegradable multifunctional polymeric biomaterial for the reconstruction of a
      gastric wall defect (polymer group; n=42). For comparison, the concentrations of
      AAG and haptoglobin were measured as well after primary wound closure of the
      gastric wall defect without biomaterial implantation (control group; n=21) and in
      rats without any surgical procedure (baseline group; n=21). The implantation
      periods were 1 week, 4 weeks and 6 months. The concentrations of AAG and
      haptoglobin were measured by an ELISA assay. Gastrointestinal complications like
      fistula, perforation or peritonitis did not occur in any of the animals. No
      statistically significant differences in the concentrations of AAG and
      haptoglobin were detected between the polymer and the control group. An adequate
      mechanical stability of the polymeric biomaterial was detectable under the
      extreme pathophysiological conditions of the stomach milieu. In further
      examinations the correlation between the intraperitoneal cytokine levels of the
      animals and the following systemic inflammatory markers should be analysed.
      Further investigations are needed to analyse the mechanisms of the tissue
      integration of a biomaterial as well as the process of the tissue remodeling and
      the influence of the immune system on these mechanisms. The knowledge of these
      processes is necessary to adapt the multifunctional biomaterial and prepare it
      thus for the use and implantation in different body locations and to develop
      novel therapeutical options in medicine.

PMID- 17502701
TI  - Contrast enhanced ultrasound eases interpretation of an unclear renal tumor in
      addition to CT, MRI and histological findings--a case report in a young patient.
AB  - Renal cancer represents accounts for approximately 3% of all adult malignancies
      with a rising incidence. Incidental diagnosis is mostly based upon ultrasound
      (US). US and Computed tomography (CT) are the standard imaging modalities for
      detecting renal cell cancer (RCC). Differentiation between malignant and benign
      renal tumors is of utmost importance. Contrast enhanced ultrasound (CUS) seems to
      be a promising new diagnostic option for diagnosis and preoperative treatment
      planning for patients with renal cancer. It is an additional examination to
      baseline ultrasound and CT. We report a case of a 37-year-old woman with a
      papillary renal cell cancer in which CUS helped to differentiate dignity of the
      tumor. CUS is an additional examination to baseline ultrasound and CT. It is a
      less invasive technique than contrast enhanced CT and shows even slight tumor
      blood flow. In addition it may allow a more rapid diagnosis, because of its
      bedside availability.

PMID- 17502702
TI  - Maximal exercise and lactate do not change red blood cell aggregation in well
      trained athletes.
AB  - Exercise and lactate usually change blood rheology, particularly red blood cell
      (RBC) deformability. The effect of lactate on RBC aggregation is unknown. The
      present study tested the in vivo effects of exercise on both lactate and RBC
      aggregation and the in vitro effects of lactate on RBC aggregation. Thirteen well
      trained athletes performed a progressive and maximal exercise test during which
      blood was sampled at rest, at 50% of maximal exercise, and at maximal exercise.
      RBC aggregation was assessed with the Myrenne aggregometer which gives two
      indexes of RBC aggregation: "M" (aggregation during stasis after shearing at 600
      s(-1)) and "M1" (facilitated aggregation at low shear rate after shearing at 600
      s(-1)). A part of the resting blood sample was also reserved to test the in vitro
      effects of three lactate concentrations (2, 4 and 10 mM). The lactate solutions
      were described in a previous study (P. Connes, D. Bouix, G. Py, C. Prefaut, J.
      Mercier, J.F. Brun and C. Caillaud, Opposite effects of in vitro lactate on
      erythrocyte deformability in athletes and untrained subjects, Clin. Hemorheol.
      Microcirc. 31 (2004), 311-318). The results demonstrated that M and M1 were
      unchanged with exercise and lactate. Therefore, lactate is able to change RBC
      deformability but not RBC aggregation.

PMID- 17502703
TI  - Hemorheological efficiency of drugs, targeting on intracellular phosphodiesterase
      activity: in vitro study.
AB  - This in vitro study was designed to examine changes of red cell microrheological
      parameters (red cell aggregation and their suspension viscosity) after cell
      incubation with some drugs having phosphodiesterase (PDE) inhibitory activity
      (pentoxifylline - 25.0 microg/ml; drotaverine - 10.0 microg/ml; vinpocetine - 5.0
      microg/ml; papaverine - 10.0 microg/ml; caffeine - 25.0 microg/ml; 3-isobutyl-1
      methylxanthine [IBMX] - 10.0 microg/ml). Concentrations of used drugs for in
      vitro red cell microrheology study were the similar with those which it could be
      possible in blood of patient after intravenous therapeutic infusion. Red blood
      cells were separated from the blood by centrifugation at 1400 g for 15 min and
      washed 3 times with phosphate buffered saline (PBS). The washed RBCs were then
      resuspended in PBS at a hematocrit of approximately 40%. In each of the research
      sessions these RBC suspensions were divided into two aliquots and exposed to: one
      of the drug at 37 degrees C for 15 min; remaining aliquot (red cell suspension
      with PBS) was kept at 37 degrees C for 15 min and served as the control. It was
      found that all of used drugs decreased red cell aggregation and their suspension
      viscosity significantly. Since IBMX and vinpocetine are the specific inhibitor
      PDE activity it might be suppose that cellular PDE is molecular target in RBCs
      for this class of drugs. The obtained data reveals evidence that drugs, acting as
      PDE inhibitors, might be considered as microrheologically positive remedies.

PMID- 17502704
TI  - Erythrocytes aggregation in healthy donors at native and standard hematocrit: the
      influence of sex, age, immunoglobulins and fibrinogen concentrations.
      Standardization of parameters.
AB  - Characteristic parameters of erythrocyte aggregation/disaggregation kinetics in
      blood samples of 200 healthy donors at native and standard hematocrit were
      studied. Average aggregation parameters for men and women at native hematocrit
      significantly differed, but these differences disappeared after hematocrit
      standardization, only maximal amplitude of aggregation (I(0)) at standard
      hematocrit in women was still less than in men (p<0.001). Though index of
      strength of largest aggregates (I(a)(2.5)) depended both on sex and age, no
      significant influence of IgG and IgM concentrations on this parameter was
      noticed. The obtained results show that suggested method can be used for
      diagnostics of rheological disorders.

PMID- 17502705
TI  - The association between hematological parameters and coronary flow reserve and
      coronary haemorheology in healthy subjects.
AB  - Studies carried out on sheep's have suggested possible effects of hematological
      parameters on coronary flow reserve (CFR). However, there is no study published
      investigating possible effects of hematological parameters and blood viscosity on
      coronary haemorheology and CFR in humans. We investigated the possible effects of
      hematological parameters on CFR using transthoracic echocardiography. METHODS:
      This study was conducted on 142 healthy subjects free of known cardiovascular
      risk factors between ages of 18-50 years. Hematological parameters were measured
      using an automated blood analyzer. Transthoracic echocardiographic examination
      including CFR measurement was performed on each subject using an Acuson Sequoia
      C256 Echocardiography System. RESULTS: The study group (142 subject) was divided
      into two according to the mean CFR values as the group with lower than mean CFR
      value and the group with upper than mean CFR value. Hematocrit (42.21+/-3.86 vs
      40.27+/-3.97, P=0.004), LDL cholesterol, hsCRP values differed between the lower
      CFR and higher CFR groups. The other hematological parameters including
      hemoglobin value were similar between the two groups. hsCRP (beta=-0.334,
      P=0.001), mitral E/A ratio (beta=0.119, P=0.024), and haematocrit (beta=-0.161,
      P=0.064) values were the independent predictors of CFR. In women's subgroup, age,
      hemoglobin, hematocrit, and hsCRP values tended to differ between the lower CFR
      and the higher CFR subgroups. In men's subgroup systolic blood pressure, hsCRP,
      and mitral E velocity were different between the two groups. CONCLUSION: In
      addition to the coronary endothelial and coronary microvascular functions,
      hematocrit and blood viscosity might have some effect on coronary haemorheology
      and CFR.

PMID- 17502706
TI  - Medical ethics.

PMID- 17502707
TI  - Specialty dentistry for the hemophiliac: is there a protocol in place?
AB  - Restorative dental care for the hemophiliac patient is of paramount importance
      for the fact that advanced dental conditions and subsequent treatments prove to
      be more complicated and risky. Quite often, dental health is neglected by
      hemophiliacs for fear of bleeding during procedures. Surprisingly, even dental
      specialists avoid these candidates and contribute to the conversion ofa simple
      dental patient to an oral surgical patient. The complexities involved in
      diagnosing a bleeding disorder and the rarity of a standardized protocol to
      handle such patients contribute to this problem. This article prescribes a simple
      protocol to diagnose bleeding disorders and a modified scheme for endodontic and
      periodontal therapy in a hemophiliac patient.

PMID- 17502708
TI  - Greater severity and extent of periodontal breakdown in 136 south Indian human
      immunodeficiency virus seropositive patients than in normal controls: a
      comparative study using community periodontal index of treatment needs.
AB  - Apart from the more or less distinctive forms of periodontal disease associated
      with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome there
      remains considerable uncertainty as to whether or not conventional destructive
      periodontitis is exacerbated in HIV positive individuals. This is especially so
      in developing countries, from which few studies have been reported. The present
      study compared the severity and extent of periodontal break down in 136 HIV
      positive individuals from Chennai, South India, with 136 age-matched controls
      from the same low socio-economic and ethnic group. All surfaces of all teeth were
      scored for the community periodontal index of treatment needs (CPITN).
      Statistical analysis was performed using SPSS package. The results of the present
      study show that CPITN is a simple, useful technique to assess periodontal status
      in immunosuppressed patients and that periodontitis is associated with
      immunosuppression and oral candidiasis. The assessment of periodontal statuscould
      thus be a useful tool in minimally invasive screening of populations for HIV
      disease, especially in those parts of the world, like India and Africa, with high
      prevalence and rising incidence.

PMID- 17502709
TI  - Evaluation of working length determination methods: an in vivo / ex vivo study.
AB  - This comparative study was done to determine the accuracy in measuring the
      working length of root canal using tactile method, electronic apex locator and
      radiographic method, in vivo and comparing the lengths so measured to the actual
      working length, ex vivo, after extraction. Thirty single-rooted teeth scheduled
      for extraction were selected for the study. After obtaining the consent from
      patients, a preoperative radiograph was taken and access opening was done.
      Working length was determined by tactile method, by using Ingle's radiographic
      method and by using a Foramatron-IV digital apex locator. The teeth were then
      extracted and the actual working length was determined by placing an endodontic
      file in the root canal 0.5 mm short of the apex. The results indicated that among
      the three methods, the electronic apex locator showed the highest accuracy and
      the highest reliability for working length determination.

PMID- 17502710
TI  - Image analysis of normal exfoliated gingival cells.
AB  - OBJECTIVE: The present study was undertaken to evaluate the nuclear diameter
      (ND), cell diameter(CD) and nuclear-cytoplasmic ratio (N:C) and their variation
      with age and sex in normal gingival smears. STUDY DESIGN: Gingival smears were
      collected from 320 apparently healthy individuals. After fixation in 95% alcohol,
      the smears were stained using standard papanicolaou laboratory procedure. The
      cell and nuclear diameters were measured using image analysis software (KSlite
      2.0). Statistical analysis of the data was done using one-way ANOVA, Students 't'
      test and Tukey-HSD procedure. RESULTS: The results showed an increase in ND from
      the 1-20 group to 21-40 age group in males. Above 40 years, there was a decrease
      in ND. In females, the ND was high in 21-40 age group; and then from 41 years, ND
      gradually decreased but the difference was not significant. The CD in males and
      females was low in the 1-20 age group and then it gradually increased. However,
      the difference was not significant between the ages 20 and 60 years. After 60,
      there was a decrease in CD. Similar changes are also seen in the ratio N:C in
      both males and females. The ND, CD and N:C irrespective of the age were high in
      females. The difference in CD was insignificant, except in the 0-20 age group,
      where females had significantly more cell diameters. Irrespective of the gender,
      the ND, CD and N:C increased from 0-20 age group to 20-40 age group. After 40,
      there is a steady decrease in ND, CD and N:C. CONCLUSION: Age-related and sex
      related alterations are observed in gingival smears.

PMID- 17502711
TI  - Assessment of periodontal status in dental fluorosis subjects using community
      periodontal index of treatment needs.
AB  - BACKGROUND: Periodontitis is multifactorial in nature. The various determinants
      of periodontal disease are age, sex, race, socioeconomic status and risk factors
      including tobacco usage and oral hygiene status. However, there is inconsistent
      epidemiological data on the periodontal status of subjects living in high
      fluoride areas. The aim of the study was to investigate the effect of dental
      fluorosis on the periodontal status using community periodontal index of
      treatment needs (CPITN), as a clinical study. The purpose of this study is to
      determine the periodontal status using CPITN index in a population aged between
      15 and 74 years residing in the high fluoride areas of Davangere district. The
      possible reasons for the susceptibility of this population to periodontal disease
      are discussed. MATERIALS AND METHODS: 1029 subjects, aged between 15 and 74 years
      suffering from dental fluorosis were assessed for their periodontal status.
      Clinical parameters recorded were OHI-S to assess the oral hygiene status,
      Jackson's fluorosis index to assess the degree of fluorosis and CPITN index to
      assess the periodontal status where treatment need was excluded. RESULTS:
      Gingivitis and periodontitis were more common in females (65.9% and
      32.8%,respectively) than in males (75.1% and 24.2%, respectively). Periodontitis
      was significantly more common in females. As the age advanced from 15 to 55 years
      and above, gingivitis reduced from 81.0 to 42.9% and periodontitis increased
      steadily from 18.0 to 57.1%, which was significant. Periodontitis was high in
      subjects with poor oral hygiene (81.3%), compared to those with good oral hygiene
      (14.5%), which was significant. As the degree of fluorosis increased, severity of
      gingivitis reduced and periodontitis increased, i.e, with A degree fluorosis,
      gingivitis was 89.4% and periodontitis 8.5%, but with F degree fluorosis the
      former was 64% and the latter 35.8%, which was statistically significant.
      CONCLUSION: The results suggest that there is a strong association of occurrence
      of periodontal disease in high-fluoride areas. The role of plaque is well
      understood in contrast to the effect of fluorides on periodontal tissues. It goes
      a long way to reason out fluoride as an important etiological agent in
      periodontal disease.

PMID- 17502712
TI  - Healing of periodontal flaps when closed with silk sutures and N-butyl
      cyanoacrylate: a clinical and histological study.
AB  - BACKGROUND: The closure of the periodontal flaps post-surgery is a necessity for
      attainment of a primary union between the flap margins and the establishment of a
      healthy dentogingival junction. N-butyl cyanoacrylate is a tissue adhesive, which
      can be used for the closure of the incised wounds to overcome the problems
      associated with conventional suture materials like silk. OBJECTIVE: The present
      study was carried out to assess the healing of the periodontal flaps when closed
      with the conventional silk sutures and N-butyl cyanoacrylate. MATERIALS AND
      METHODS: The study was carried out on 24 patients who needed flap surgical
      procedure for pocket therapy. RESULTS: It was found that healing with the
      cyanoacrylate is associated with less amount of inflammation during the first
      week when compared with silk. However, over a period of 21 days to 6 weeks, the
      sites treated with both the materials showed similar healing patterns.
      CONCLUSION: It can be concluded that cyanoacrylate aids in early initial healing.

PMID- 17502713
TI  - A study of the reasons for irregular dental attendance in a private dental
      college in a rural setup.
AB  - The mouth is regarded as a mirror and the gateway to health. Integration is
      required between the dental practitioner and the patient, if good dental health
      is to be attained. Various treatment modalities of late frequently require
      appointments, which are more than one in number for completion of the entire
      treatment program. This study was taken up to determine the impact of reported
      dental attendance patterns of patients on the oral health and treatment quality
      in teaching hospitals and also on the quality of life in rural areas. AIMS AND
      OBJECTIVES: 1. To assess the reasons for irregular dental care in the patients
      attending the clinics in teaching hospitals. 2. To assess the satisfaction of the
      patient as regards the treatment rendered in the teaching institutes. 3. To
      correlate the gender of the patient with the regularity in the recall attendance.
      MATERIALS AND METHODS: A hospital-based cross-sectional study was conducted using
      a systematic random sampling method and every alternate subject was selected from
      the patients attending the OPD of Department of Periodontics and Community
      Dentistry. The data was collected using the interview method with the help of a
      structured, pretested questionnaire. RESULTS AND CONCLUSION: Out of 288 patients,
      94 failed to attend the recall appointments. In these 94 patients, various
      reasons for not attending recall were assessed and lack of time was found to be
      the most common reason for non-attendance. Relationship between age and reasons
      for not reporting was found to be significant (P < 0.01). Patient satisfaction
      survey showed that 51.54% of the patients were satisfied with the dental
      treatment rendered. The present study also showed that males are more prompt in
      attending recall appointments as compared to females. A positive and significant
      correlation between literacy and patient reporting status was found (P< 0.01).

PMID- 17502714
TI  - Root development of permanent lateral incisor in cleft lip and palate children: a
      radiographic study.
AB  - OBJECTIVE: The objective of this study was to compare the root development of
      lateral incisor on the cleft side with the root development of its contralateral
      tooth in cleft lip and palate children. SETTING: Cleft lip and palate wing,
      Meenakshi Ammal Dental College and Hospital, Chennai, South India. MATERIALS AND
      METHODS: A sample of 96 orthopantamograms of patients with unilateral orbilateral
      cleft lip and/or cleft palate was selected, regardless of sex and race. MAIN
      OUTCOME MEASURE: Orthopantamograms were analyzed for root development of lateral
      incisor on the cleft and non cleft side. Associated anomalies like hypodontia,
      supernumerary teeth, malformed lateral incisors and root development of canine,
      if present, were recorded. FINDINGS AND CONCLUSIONS: Root development of
      permanent lateral incisor was delayed on the cleft side compared to the non cleft
      side. There was a statistically significant relationship between levels of root
      development of lateral incisors on the cleft side within the different study
      groups(P < 0.05). Incidence of hypodontia increased in proportion to cleft
      severity. Frequency of missing second premolars, supernumerary teeth and
      malformed lateral incisors increased in cleft lip and palate patients. Root
      development of canine showed a slight delay on the cleft side when compared to
      the canine on the noncleft side.

PMID- 17502715
TI  - Restoration of a vertical tooth fracture and a badly mutilated tooth using canal
      projection.
AB  - Management of vertically fractured tooth or a perforation frequently poses
      problem during endodontic management. Such teeth often need a pre-endodontic
      restoration prior to initiation of root canal therapy to aid in the placement of
      rubber dam clamp. This paper describes a simple method of placement of a pre
      endodontic restoration using the canal projection technique using hollow metallic
      needles as sleeves.

PMID- 17502716
TI  - High-flow vascular malformation of the mandible.

PMID- 17502717
TI  - Culture methods of glomerular podocytes.
AB  - Podocytes (glomerular visceral epithelial cells) cover the exterior surface of
      the glomerular capillaries and contribute to the glomerular filtration membrane.
      Failure of podocyte function is involved in the progression of chronic glomerular
      disease; accordingly, research interest into podocyte biology is driven by the
      need for better protection and perhaps recovery of these cells in renal diseases.
      This review aims at summarizing available techniques for podocyte cell cultures
      from both the past and present, with special attention to the currently used
      methods. The establishment of classical primary cultures is based on isolation of
      glomeruli by differential sieving. Plating of glomeruli onto a collagen surface
      is followed by an outgrowth of cobblestone-like cells that, after replating,
      differentiate into arborized, mature podocytes. Currently, the majority of
      research studies use immortalized podocytic cell lines most often derived from
      transgenic mice bearing a conditional immortalizing gene. The podocytes can also
      be collected and cultured from healthy or diseased animal or patient urine. The
      urinary podocytes obtained from subjects with active glomerulopathies display
      higher proliferation potential and viability in vitro, perhaps due to disease
      induced transdifferentiation. Finally, a list of phenotypic markers useful for
      identification and characterization of the cultured podocytic elements is
      provided.

PMID- 17502718
TI  - Care of patients coinfected with HIV and hepatitis C virus: 2007 updated
      recommendations from the HCV-HIV International Panel.

PMID- 17502719
TI  - Polymorphisms in IRF-1 associated with resistance to HIV-1 infection in highly
      exposed uninfected Kenyan sex workers.
AB  - OBJECTIVE: To determine the correlation between polymorphisms in the IL-4 gene
      cluster and resistance to HIV-1 infection. DESIGN: : A cross-sectional genetic
      analysis of polymorphisms within the IL-4 gene cluster was conducted in a well
      described female sex worker cohort from Nairobi, Kenya, known to exhibit
      differential susceptibility to HIV-1 infection. METHODS: Microsatellite
      genotyping was used to screen six microsatellite markers in the IL-4 gene cluster
      for associations with HIV-1 resistance. Further analysis of the interferon
      regulatory factor 1 (IRF-1) gene was conducted by genomic sequencing.
      Associations between IRF-1 gene polymorphisms and the HIV-1 resistance phenotype
      were determined using the chi-square test and Kaplan-Meier survival analysis. The
      functional consequence of IRF-1 polymorphism was conducted by quantitative
      Western blot. RESULTS: Three polymorphisms in IRF-1, located at 619, the
      microsatellite region and 6516 of the gene, showed associations with resistance
      to HIV-1 infection. The 619A, 179 at IRF-1 microsatellite and 6516G alleles were
      associated with the HIV-1-resistant phenotype and a reduced likelihood of
      seroconversion. Peripheral blood mononuclear cells from patients with protective
      IRF-1 genotypes exhibited significantly lower basal IRF-1 expression and reduced
      responsiveness to exogenous IFN-gamma stimulation. CONCLUSION: Polymorphisms in
      the IRF-1 gene are associated with resistance to infection by HIV-1 and a lowered
      level of IRF-1 protein expression. This study adds IRF-1, a transcriptional
      immunoregulatory gene, to the list of genetic correlates of altered
      susceptibility to HIV-1. This is the first report suggesting that a viral
      transcriptional regulator might contribute to resistance to HIV-1. Further
      functional analysis on the role of IRF-1 polymorphisms and HIV-1 resistance is
      underway.

PMID- 17502720
TI  - Nef alleles from children with non-progressive HIV-1 infection modulate MHC-II
      expression more efficiently than those from rapid progressors.
AB  - BACKGROUND: It has been established that defective nef genes and differences in
      the Nef-mediated downmodulation of CD4 and MHC-I cell surface expression can be
      associated with different rates of HIV-1 disease progression. OBJECTIVE: To
      evaluate whether nef alleles derived from perinatally HIV-1-infected children
      showing no, slow or rapid disease progression differ in their abilities to
      downmodulate mature MHC-II or to upregulate the invariant chain (Ii) associated
      with immature MHC-II complexes. METHODS: Nef alleles derived from HIV-1-infected
      children were cloned into expression vectors and proviral HIV-1 constructs co
      expressing Nef and enhanced green fluorescence protein via an internal ribosomal
      entry site. Nef-mediated modulation of CD4, MHC-I, MHC-II or Ii surface
      expression was analysed by flow cytometric analysis of Jurkat T cells, monocytic
      THP-1 cells, CD4 T cells and macrophages transduced with vesicular stomatitis
      virus G-pseudotyped HIV-1 nef variants or transiently transfected HeLa class II
      transactivator cells. RESULTS: : Nef alleles derived from HIV-1-infected children
      with non-progressive infection were significantly more active in the upregulation
      of Ii and downregulation of MHC-II than those derived from rapid progressors.
      CONCLUSION: Nef alleles particularly active in interfering with MHC-II antigen
      presentation are more frequently found in perinatally HIV-1-infected non
      progressors than rapid progressors. Possibly in the context of an immature host
      immune system, strongly impaired MHC-II function might contribute to lower levels
      of immune activation and a decelerated loss of CD4 T cells.

PMID- 17502721
TI  - HIV suppression by HAART preserves cognitive function in advanced, immune
      reconstituted AIDS patients.
AB  - INTRODUCTION: HIV can damage neurons leading to cognitive impairment.
      Epidemiological observations suggest that neuropsychological impairment might
      progress despite successful HAART therapy, but available prevalence estimates are
      based on populations that were selected for impairment. METHODS: Of 433 advanced
      AIDS patients with documented immune reconstitution (CD4 lymphocyte counts < 50
      before and > 100 cells/microl after HAART), 286 had brief assessments of
      cognition (Trailmaking A/B and Digit Symbol Tests) at least once, no confounding
      neurological conditions, and available neuropsychological norms with
      comprehensive demographic corrections. At entry, most were immune reconstituted
      on HAART (median CD4 cell count 230 cells/microl) and HIV was suppressed (65% <
      500; only 14% > 20 000 RNA copies/ml). RESULTS: Over one quarter (27%) of
      participants exhibited impairment at their initial neuropsychological assessment,
      a rate nearly twice that expected in a normal (HIV-uninfected) reference
      population (14%). These impaired participants did not differ from the unimpaired
      group with respect to age, sex, education, race, CD4 lymphocyte counts, or HIV
      RNA levels. Improved performance on neuropsychological tests was documented over
      a 2-year period 3-5 years after initiating HAART. This improvement was marginally
      associated with the continued or improving control of plasma HIV-RNA levels, but
      not with concurrent levels of immune recovery (CD4 lymphocyte counts).
      CONCLUSION: Most advanced AIDS patients responding to HAART for prolonged periods
      have stable or improving cognition, but remain more likely to be impaired than
      the general population. During HAART, improving test performance probably
      reflects both practice effects and continuing neurological recovery after more
      than 3 years of HAART.

PMID- 17502722
TI  - Chronic renal failure among HIV-1-infected patients.
AB  - BACKGROUND: The role of exposure to antiretrovirals in chronic renal failure
      (CRF) is not well understood. Glomerular filtration rates (GFR) are estimated
      using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD)
      equations. METHODS: Baseline was arbitrarily defined as the first recorded GFR;
      patients with two consecutive GFR < or = 60 ml/min per 1.73 m(2) were defined as
      having CRF. Logistic regression was used to determine odds ratio (OR) of CRF at
      baseline. ART exposure (yes/no or cumulative exposure) prior to baseline was
      included in multivariate models (adjusted for region of Europe, age, prior AIDS,
      CD4 cell count nadir, viral load, hypertension and use of nephrotoxic anti
      infective therapy). RESULTS: Using CG, the median GFR at baseline (n = 4474) was
      94.4 (interquartile range, 80.5-109.3); 158 patients (3.5%) had CRF. Patients
      with CRF were older (median, 61.9 versus 43.1 years), had lower CD4 cell count
      nadirs (median, 80 versus 137 cells/microl), and were more likely to be diagnosed
      with AIDS (44.3 versus 30.4%), diabetes (16.5 versus 4.3%) or hypertension (53.8
      versus 26.4%), all P < 0.001. In a multivariate model any use of indinavir [odds
      ratio (OR) 2.49; 95% confidence interval (CI), 1.62-3.83] or tenofovir (OR, 2.18;
      95% CI, 1.25-3.81) was associated with increased odds of CRF, as was cumulative
      exposure to indinavir (OR, 1.15 per year of exposure; 95% CI, 1.06-1.25) or
      tenofovir (OR, 1.60; 95% CI, 1.20-2.15). Highly consistent results were seen
      using the MDRD formula. CONCLUSIONS: Among antiretrovirals, only exposure to
      indinavir or tenofovir was associated with increased odds of CRF. We used a
      confirmed low GFR to define CRF to increase the robustness of our analysis,
      although there are several potential biases associated with this cross-sectional
      analysis.

PMID- 17502723
TI  - Alterations in circulating osteoimmune factors may be responsible for high bone
      resorption rate in HIV-infected children and adolescents.
AB  - OBJECTIVES: Bone metabolism derangements have been reported in HIV-infected
      children and adolescents. Nuclear factor kappa B ligand (RANKL) and
      osteoprotegerin potently stimulate and inhibit, respectively, osteoclast
      formation and activity. We investigated the possible role of RANKL and
      osteoprotegerin on bone metabolism alterations in paediatric patients. DESIGN: A
      prospective controlled longitudinal study. Measurements were obtained before and
      6 months after switching antiretroviral regimen. METHODS: We studied 27
      vertically HIV-infected children and adolescents (aged 4.9-17.3 years) on long
      term HAART (70.1 +/- 1.5 months). All patients received lamivudine, stavudine and
      one protease inhibitor (PI). During follow-up, the PI was replaced with efavirenz
      and stavudine with tenofovir. We also enrolled 336 healthy children, aged 4.8
      17.9 years. Concentrations of bone-specific alkaline phosphatase (BALP), N
      terminal telopeptide of type I collagen (NTx), RANKL, and osteoprotegerin were
      measured at baseline and 6 months after switching. RESULTS: BALP serum
      concentrations and NTx urine levels of HIV-infected patients were significantly
      higher than those of healthy children both at baseline and after 6 months (P <
      0.001). Baseline osteoprotegerin and RANKL concentrations of HIV-infected
      patients were significantly higher than in healthy children (P < 0.0001). Both
      concentrations decreased after 6 months, and RANKL levels were no longer
      different to controls. At baseline the RANKL/osteoprotegerin ratio was
      significantly higher (P = 0.02) in HIV-infected children (0.27 +/- 0.07) compared
      with healthy children (0.078 +/- 0.01). CONCLUSION: A marked alteration in the
      RANKL/osteoprotegerin system is present in patients receiving PI-based HAART.
      Short-term data indicate that replacing stavudine and PI with tenofovir and
      efavirenz restores the RANKL/osteoprotegerin equilibrium, and may thus lead to a
      reduction in the bone resorption rate.

PMID- 17502724
TI  - Progression of carotid artery intima-media thickening in HIV-infected and
      uninfected adults.
AB  - OBJECTIVES: To compare the rate of change in intima-media thickness (IMT) of the
      carotid artery among uninfected subjects and HIV-infected subjects receiving or
      not receiving protease inhibitor (PI) regimens over a 144 week period. DESIGN:
      This prospective, matched cohort study enrolled 133 subjects into 45 triads
      (groups of three subjects matched by age, sex, race/ethnicity, smoking status,
      blood pressure, and menopause) from university based outpatient HIV clinics. Each
      triad consisted of one subject from each of the following groups: 1, HIV-infected
      subjects with continuous use of PI therapy for > or = 2 years; 2, HIV-infected
      subjects without prior PI use; 3, HIV-uninfected subjects. METHODS: Standardized
      ultrasound images of carotid IMT were collected at weeks 0, 2, 24, 48, 72, 96,
      and 144. The main outcome was the yearly progression rate of carotid IMT
      (mm/year). RESULTS: The median yearly IMT progression rate in groups 1, 2, and 3
      was 0.0096, 0.0058, and 0.0085 mm/year, respectively. There were no statistically
      significant differences in progression between groups 1 and 2, or between the
      combined HIV-positive groups and the HIV-negative control group. A multicovariate
      model examining predictors of progression in carotid IMT among all subjects
      contained low density lipoprotein cholesterol and homocysteine. Among HIV
      subjects, predictors included nadir CD4 cell count and ritonavir use.
      CONCLUSIONS: HIV infection and PI use did not contribute substantially to the
      rate of carotid IMT progression in our matched study.

PMID- 17502725
TI  - Immediate versus delayed polyalkylimide gel injections to correct facial
      lipoatrophy in HIV-positive patients.
AB  - OBJECTIVE: To evaluate the safety and efficacy of polyalkylimide gel (PAIG) in
      the treatment of HIV-associated facial lipoatrophy. DESIGN: A randomized, open
      label, single-centre study. METHODS: HIV-positive individuals with facial
      lipoatrophy (based on physician assessment) were randomly assigned to immediate
      (weeks 0 and 6) or delayed (weeks 12 and 18) PAIG injections administered into
      the subcutaneous plane. Outcome measures included a change in facial lipoatrophy
      severity scores (five-point scale), adverse events, photographic assessment, and
      changes in quality of life (QoL), depression and anxiety using validated surveys.
      RESULTS: Thirty-one patients (median age 48 years, 97% male) were enrolled and
      completed 48 weeks of follow-up. Overall, the median volume of product injected
      bilaterally was 16.0 ml. Adverse events, including swelling, redness, bruising
      and pain, were mild, and resolved after a median of 3 days. There were no cases
      of necrosis, nodules or infection. Compared with patients randomly assigned to
      delayed treatment, patients in the immediate therapy group had significantly
      lower physician-rated facial lipoatrophy scores (0 versus 2; P < 0.0001),
      improved QoL (P = 0.01), and lower anxiety (P = 0.02) at week 12. At week 48,
      median physician and patient facial lipoatrophy scores were 0 and 1,
      respectively, for the entire cohort, and were not significantly different between
      the groups. Significant improvements in patient anxiety (P = 0.001) and
      depression (P = 0.01) were observed from baseline to week 48. CONCLUSION:
      Treatment with PAIG was effective and safe and led to improvements in facial
      lipoatrophy grading, QoL, anxiety and depression scores in HIV-infected patients
      with facial lipoatrophy.

PMID- 17502726
TI  - Impact of genotypic drug resistance mutations on clinical and immunological
      outcomes in HIV-infected adults on HAART in West Africa.
AB  - OBJECTIVES: To analyse the association between the presence of resistance
      mutations and treatment outcomes. The impact of HIV-1 drug resistance mutations
      in African adults on HAART has so far never been reported. METHODS: In 2004 in
      Abidjan, Cote d'Ivoire, 106 adults on HAART had plasma viral load measurements.
      Patients with detectable viral loads had resistance genotypic tests. Patients
      were followed until 2006. Main outcomes were serious morbidity and immunological
      failure (CD4 cell count < 200 cells/microl). RESULTS: At study entry, the median
      previous time on HAART was 37 months and the median CD4 cell count was 266
      cells/microl; 58% of patients had undetectable viral loads, 20% had detectable
      viral loads with no major resistance mutations, and 22% had detectable viral
      loads with one or more major mutations. The median change in CD4 cell count
      between study entry and study termination was +129 cells/microl in patients with
      undetectable viral loads, +51 cells/microl in those with detectable viral loads
      with no mutations and +3 cells/microl in those with detectable viral loads with
      resistance mutations. Compared with patients with undetectable viral loads, those
      with detectable viral loads with resistance mutations had adjusted hazard ratios
      of immunological failure of 4.32 (95%CI 1.38-13.57, P = 0.01). One patient died.
      The 18-month probability of remaining free of morbidity was 0.79 in patients with
      undetectable viral loads and 0.69 in those with resistance mutations (P = 0.19).
      CONCLUSION: In this setting with restricted access to second-line HAART, patients
      with major resistance mutations had higher rates of immunological failure, but
      most maintained stable CD4 cell counts and stayed alive for at least 20 months.

PMID- 17502727
TI  - Antiretroviral drug resistance, HIV-1 tropism, and HIV-1 subtype among men who
      have sex with men with recent HIV-1 infection.
AB  - OBJECTIVE: Antiretroviral drug treatment may be complicated in individuals
      infected with antiretroviral drug-resistant or non-subtype B HIV-1 strains. HIV-1
      tropism may also affect disease progression. We analyzed antiretroviral drug
      resistance, HIV-1 subtype, and HIV-1 tropism among 195 men who have sex with men
      from six major cities in the United States, using samples collected within 6
      months of HIV-1 seroconversion (1999-2003). METHODS: HIV-1 genotyping was
      performed using the ViroSeq HIV-1 Genotyping System. HIV-1 tropism was determined
      using a commercial assay. HIV-1 subtyping was performed by phylogenetic analysis
      of pol region sequences. RESULTS: Thirty-one (15.9%) of the men had evidence of
      antiretroviral drug resistance. Seven (3.6%) men had multi-class resistance,
      including three (1.5%) with resistance to all three antiretroviral drug classes.
      We found no statistically significant association of antiretroviral drug
      resistance with demographic factors, sexual practices, self-reported sexually
      transmitted infections, use of recreational drugs, or use of antiretroviral drug
      post-exposure prophylaxis. All samples were HIV-1 subtype B. Four men had CXCR4
      using HIV-1 strains. One man with a CXCR4-using strain also had antiretroviral
      drug resistance. CONCLUSIONS: Antiretroviral drug resistance is relatively common
      among recently infected men who have sex with men in the United States. CXCR4
      using strains were detected in a small number of these infections, which were all
      subtype B HIV-1.

PMID- 17502728
TI  - The effect of adherence on the association between depressive symptoms and
      mortality among HIV-infected individuals first initiating HAART.
AB  - OBJECTIVE: To determine the impact of depressive symptoms on mortality among
      HIV/AIDS patients first initiating HAART and the potential role of patient
      adherence as a confounder and effect modifier in this association. METHODS: The
      study comprised HIV-positive individuals who were first prescribed HAART between
      August 1996 and June 2002. Depressive symptoms were assessed using the Center for
      Epidemiologic Studies Depression Scale. Cox proportional hazards models were used
      to determine the association between depressive symptoms, adherence and all-cause
      mortality while controlling for several baseline confounding factors. RESULTS: A
      total of 563 participants met the study inclusion criteria. Of these subjects,
      51% had depressive symptoms at baseline and 23% of participants were less than
      95% adherent in the first year of follow-up. The overall all-cause mortality rate
      was 10%. Multivariate analysis showed that individuals with depressive symptoms
      and adherence < 95% were 5.90 times (95% confidence interval, 2.55-13.68) more
      likely to die than adherent patients with no depressive symptoms. The estimated
      median model-based survival probabilities stratified by adherence and depressive
      symptoms levels ranged from 81% (interquartile range, 72-89%) for depressive
      symptoms and adherence < 95% to 97% (interquartile range, 94-98%) for no
      depressive symptoms and adherence > or = 95%. CONCLUSION: The results indicate
      that both depressive symptoms and adherence were associated with shorter survival
      among individuals with HIV accessing HAART. Given the high prevalence of
      depressive symptoms in HIV-positive patients and a strong association with
      adherence, the findings support improvement in the diagnosis and treatment of
      depression as well as adherence in order to maximize the effectiveness of HAART.

PMID- 17502729
TI  - Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART:
      collaborative analysis of prospective studies.
AB  - OBJECTIVE: To estimate the prognosis over 5 years of HIV-1-infected, treatment
      naive patients starting HAART, taking into account the immunological and
      virological response to therapy. DESIGN: A collaborative analysis of data from 12
      cohorts in Europe and North America on 20,379 adults who started HAART between
      1995 and 2003. METHODS: Parametric survival models were used to predict the
      cumulative incidence at 5 years of a new AIDS-defining event or death, and death
      alone, first from the start of HAART and second from 6 months after the start of
      HAART. Data were analysed by intention-to-continue-treatment, ignoring treatment
      changes and interruptions. RESULTS: During 61 798 person-years of follow-up, 1005
      patients died and an additional 1303 developed AIDS. A total of 10 046 (49%)
      patients started HAART either with a CD4 cell count of less than 200 cells/microl
      or with a diagnosis of AIDS. The 5-year risk of AIDS or death (death alone) from
      the start of HAART ranged from 5.6 to 77% (1.8-65%), depending on age, CD4 cell
      count, HIV-1-RNA level, clinical stage, and history of injection drug use. From 6
      months the corresponding figures were 4.1-99% for AIDS or death and 1.3-96% for
      death alone. CONCLUSION: On the basis of data collected routinely in HIV care,
      prognostic models with high discriminatory power over 5 years were developed for
      patients starting HAART in industrialized countries. A risk calculator that
      produces estimates for progression rates at years 1 to 5 after starting HAART is
      available from www.art-cohort-collaboration.org.

PMID- 17502730
TI  - Correlates of suicidal ideation among HIV-positive persons.
AB  - OBJECTIVES: The present investigation sought to determine the extent to which
      demographic characteristics, illness-related burdens, alcohol and other substance
      use, and psychosocial factors are independently associated with suicidal ideation
      in HIV-positive individuals. DESIGN: HIV-positive individuals in four US cities
      (San Francisco, Los Angeles, Milwaukee, and New York City) were screened between
      July 2000 and January 2002 for recruitment into a randomized behavioral
      prevention trial. Utilizing data from this screening visit, rates and correlates
      of suicidal ideation were examined in a diverse sample of 2909 HIV-positive
      individuals. METHODS: Using binary logistic regression study sites, demographic
      characteristics, illness-related burdens, alcohol and substance use, and
      psychosocial factors were entered as predictors of suicidal ideation. This cross
      sectional model thus examined the independent effects of each factor. RESULTS:
      Approximately one-fifth (19%) of participants reported thoughts of suicide in the
      past week. We observed that participants who were not heterosexual, rated HIV
      related symptoms and medication side effects as more severe, reported regular
      marijuana use, and described elevated affective symptoms of depression were those
      who were more likely to report suicidal ideation. Conversely, participants who
      identified as Hispanic/Latino, individuals in a primary romantic relationship,
      and those who reported greater self-efficacy for coping were less likely to
      report suicidal ideation. CONCLUSION: Suicidal ideation among HIV-positive
      individuals is relatively common and is associated with multiple factors. These
      independent correlates may assist with identifying HIV-positive individuals who
      are at increased risk of suicidal ideation so that they may be assessed regularly
      and referred for psychological treatment when appropriate.

PMID- 17502731
TI  - When to switch for antiretroviral treatment failure in resource-limited settings?

PMID- 17502732
TI  - Increased haemoglobin A2 percentage in HIV infection: disease or treatment?
AB  - An elevated haemoglobin A2 percentage has been reported in HIV-infected patients,
      possibly attributable to therapy. In cross-sectional and cohort studies we have
      established that A2 is often elevated in untreated patients; a further rise
      during treatment is attributable specifically to zidovudine. The haemoglobin A2
      may be high enough to lead to a misdiagnosis of beta thalassemia trait if there
      is a lack of awareness of this unexpected effect of HIV infection and its
      treatment.

PMID- 17502733
TI  - WHO HIV clinical staging or CD4 cell counts for antiretroviral therapy
      eligibility assessment? An evaluation in rural Rakai district, Uganda.
AB  - The ability of WHO clinical staging to predict CD4 cell counts of 200
      cells/microl or less was evaluated among 1221 patients screened for
      antiretroviral therapy (ART). Sensitivity was 51% and specificity was 88%. The
      positive predictive value was 64% and the negative predictive value was 81%.
      Clinical criteria missed half the patients with CD4 cell counts of 200
      cells/microl or less, highlighting the importance of CD4 cell measurements for
      the scale-up of ART provision in resource-limited settings.

PMID- 17502734
TI  - Key amprenavir resistance mutations counteract dramatic efficacy of darunavir in
      highly experienced patients.
AB  - In highly experienced HIV-1-infected patients, a ritonavir-boosted darunavir
      containing regimen was associated with dramatic immunological and virological
      efficacy. Patients harbouring viruses with amprenavir-specific resistance
      profiles, such as I50V or V32I + I47V, failed on a darunavir/ritonavir-containing
      regimen. These key amprenavir mutations were also selected at the time of
      failure, suggesting their impact on darunavir efficacy.

PMID- 17502735
TI  - An outbreak of HIV-1 subtype G among Italian injecting drug users.
AB  - We describe an outbreak of subtype G among injecting drug users (IDU) in northern
      Italy newly infected with HIV. We analysed pol gene sequences from samples of 139
      individuals from different risk groups. Non-B subtypes were more frequently
      detected among IDU than in homosexual or heterosexual contacts. All G subtypes
      but one were found among IDU. The phylogenetic analysis indicated that the
      outbreak was of monophyletic origin and was caused by HIV-1 strains similar to
      those from western Africa.

PMID- 17502736
TI  - Atazanavir-associated nephrolithiasis: cases from the US Food and Drug
      Administration's Adverse Event Reporting System.
AB  - The risk of nephrolithiasis associated with atazanavir is not well characterized.
      The US Food and Drug Administration's Adverse Event Reporting System was searched
      for reports of nephrolithiasis in HIV-infected patients taking an atazanavir
      based regimen. Thirty cases were identified. Many patients required
      hospitalization for management, including lithotripsy, ureteral stent insertion,
      or endoscopic stone removal. Some cases of nephrolithiasis resulted in atazanavir
      discontinuation. Healthcare professionals and patients should be informed that
      nephrolithiasis is a possible adverse event with atazanavir.

PMID- 17502737
TI  - Serosorting can potentially increase HIV transmissions.
AB  - The effectiveness of a serosorting strategy for HIV prevention depends on the
      accuracy of individuals' serostatus disclosures. We modeled the risks of sexual
      transmission of HIV under various circumstances differing by the type of
      disclosures made. Accounting for rates of unrecognized HIV infection, treatment
      status and differences in infectivity by stage of infection, we found that
      serosorting can increase the transmission risk for some groups.

PMID- 17502738
TI  - Cryptosporidial diarrhoea in two HIV-infected patients: potential efficacy of
      rifampicin for successful treatment.

PMID- 17502739
TI  - False-positive HIV antibody results with ultrasensitive serological assays in
      uninfected infants born to mothers with HIV.

PMID- 17502740
TI  - Lack of immune recovery in HIV/Leishmania co-infection treated with human
      recombinant IL-2.

PMID- 17502741
TI  - Antiretroviral therapy: what about food?

PMID- 17502742
TI  - Response to "Nifedipine-lopinavir/ritonavir severe interaction: a case report".

PMID- 17502743
TI  - Amplification of HIV-induced depletion of CD4 T cells of gut-associated lymphoid
      tissue by enteric bacteria.

PMID- 17502744
TI  - The impact of silicone hydrogel materials on overnight corneal swelling.
AB  - PURPOSE: To identify the corneal swelling response associated with silicone
      hydrogel contact lens wear. METHODS: Twenty-five subjects were recruited to
      participate in this single-center, controlled, single-masked, clinical trial. The
      corneal swelling response was evaluated by central corneal pachymetry after
      overnight wear of balafilcon A, etafilcon A, lotrafilcon A, senofilcon A, and no
      lens wear. More specifically, after 8 hours of closed-eye wear of each material,
      corneal thickness was measured immediately on eye opening, in addition to the
      first 4 hours of open-eye wear. Paired t tests were used to compare the swelling
      response from each condition to that associated with senofilcon A, and given the
      numerous statistical comparisons, a P value of <or=0.01 was considered
      significant. RESULTS: At eye opening, there was no difference in the swelling
      response when comparing balafilcon A (1.35%), lotrafilcon A (1.22%), or no lens
      wear (0.77%) to senofilcon A (1.40%), although the swelling response associated
      with etafilcon A was significantly greater (P<0.001) than that associated with
      senofilcon A. There were no differences between balafilcon A, lotrafilcon A, and
      no lens wear compared to senofilcon A during the open-eye deswelling period.
      However, 1 hour after eye opening, corneal swelling remained significantly
      greater with etafilcon A than with senofilcon A (1.76% vs. -0.51%, respectively,
      P=0.01), although no other time-specific comparisons differed. CONCLUSIONS:
      Silicone hydrogel lenses, with high oxygen transmissibilities, are associated
      with very little corneal swelling after overnight wear of the lenses.

PMID- 17502745
TI  - Severe acanthamoeba keratitis after overnight orthokeratology.
AB  - PURPOSE: To document a clinical case of Acanthamoeba keratitis associated with
      orthokeratology overnight lens wear that resulted in severe, permanent vision
      loss. METHODS: Case report. RESULTS: At the age of 11 years, a boy received a
      spectacle correction for the following refractive error: -3.25 -0.50 x090 in the
      right eye and -3.50 -0.25 x 040 in the left eye. Alternative wear of daily-wear,
      disposable, soft contact lenses and rigid gas-permeable lenses was used for
      athletic activities to the age of 16 years. Between the ages of 16 and 19 years,
      the patient wore Boston Equalens 2c27 (type Percision Corneal Molding - 51)
      lenses with a base curve of 9.25, power of +2.50 diopters (D), and diameter of
      10.6 mm in the right eye and a base curve of 9.15, power of +3.00 D, and diameter
      of 10.6 mm in the left eye for overnight orthokeratology wear. A corneal ulcer in
      the left eye was noted on November 13, 2004 (age of 19 years) and confirmed as
      Acanthamoeba infection by confocal microscopy on February 15, 2005, when triple
      topical therapy (Brolene, polyhexamethylbiguanide, and chlorhexidene) was
      initiated. Vision deteriorated to light perception with accurate projection by
      cessation of therapy on March 28, 2006. Additional complications included
      secondary angle-closure glaucoma, treated with an Ahmed tube shunt on April 12,
      2005, and a mature cataract. CONCLUSIONS: The important message conveyed by this
      case was the finding that for several years, unknown to his eye care physicians,
      the patient cleaned his lenses with the Boston Cleaning System, as instructed,
      but followed this step with a routine rinse with tap water and storage in tap
      water in his lens case, which was not replaced or cleaned. The tragic loss of
      vision in this case probably could have been prevented by focused attention to
      lens hygiene by the patient, parents, and practitioner. Such heightened scrutiny
      is critically important in orthokeratology rigid lens wear, especially in
      children, independent of the lens polymer or fitting algorithm used.

PMID- 17502746
TI  - Experimentally increased intraocular pressure using digital forces.
AB  - PURPOSE: To examine the reliability of an experimental method for increasing
      intraocular pressure (IOP) that could be used during videokeratography. METHODS:
      Two levels of digital force ("light" and "firm") were applied by each subject to
      the temporal sclera of the right eye through the adnexal skin. Noncontact
      tonometry was used to record IOP increments obtained for samples of 15
      measurements with each level of digital force. The subject was advised of the IOP
      recorded after each measurement. Because "with-result-feedback" increments in IOP
      would not be possible during videokeratography, a second, "without-result
      feedback" series was recorded 3 minutes later to examine the reliability of the
      induced IOP increments. The authors alternated the roles of subject and examiner.
      RESULTS: The mean normal readings were 19.4 mm Hg (C.W.M.) and 11.7 mm Hg
      (G.C.B.). The mean IOPs recorded under with-result-feedback conditions for light
      and firm digital forces were 27.2 mm Hg and 58.3 mm Hg (C.W.M.) and 27.1 mm Hg
      and 52.1 mm Hg (G.C.B.), respectively. Coincidentally, light digital forces were
      found to induce IOP increments for G.C.B. that were similar to those that would
      be expected to occur during 5.5 g weighted Schiotz tonometry. The 95% confidence
      limits for IOP increments under with-result-feedback conditions for light and
      firm digital forces were 33% to 47% and 187% to 215% (C.W.M.) and 116% to 146%
      and 303% to 388% (G.C.B.), respectively. The means of the without-result-feedback
      IOP increments for the two levels of digital force, and for each subject, all
      fell within these 95% confidence limits. CONCLUSIONS: For trained subjects,
      digital forces on the eye appear to allow an examination of the influence of IOP
      increments on anterior corneal surface curvature. The mean IOP increments for the
      two levels of digital force (+40% and +200% [C.W.M.] and +132% and +345%
      [G.C.B.]) appear to permit videokeratography at higher IOP levels and across a
      wider range than those previously examined in vivo.

PMID- 17502747
TI  - Corneal curvature stability with increased intraocular pressure.
AB  - PURPOSE: To examine the corneal shape and ocular refraction under conditions of
      increased intraocular pressure (IOP) and to consider the possible influences of
      direct digital forces, corneal thickness, limbal and scleral rigidity, and the
      duration and frequency of IOP loading on the results. METHODS: Forces applied
      digitally to the temporal sclera were used to obtain 15 optimized
      videokeratographic records for two subjects under different levels of IOP
      loading. Stability of refraction was also examined under the same conditions.
      RESULTS: Relative to normal IOP, four levels of IOP increments were induced: 43%
      to 61% (from a normal 18.8 mm Hg to approximately 28.6 mm Hg), 119% to 153% (from
      a normal 12.2 mm Hg to approximately 28.8 mm Hg), 181% to 213% (from a normal
      18.8 mm Hg to approximately 55.8 mm Hg), and 374% to 443% (from a normal 12.2mm
      Hg to approximately 62.1 mm Hg). Significant changes in response to IOP loading
      were few in number and of a minor degree. For example, the maximum simulated
      keratometry change was 0.20 diopters (D), and the maximum change in refractive
      error recorded was 0.625 D in cylinder. CONCLUSIONS: Corneal shape and refraction
      were found to show only minor evidence of instability under conditions of IOP
      loading. The small number and minor degree of corneal changes recorded under IOP
      loading suggest that under these conditions of measurement, corneal stability may
      be the result of stress stiffening. However, mechanisms for corneal shape changes
      that depend on limbal and scleral rigidity may also contribute to corneal shape
      stability.

PMID- 17502748
TI  - Quantity and conformation of lysozyme deposited on conventional and silicone
      hydrogel contact lens materials using an in vitro model.
AB  - PURPOSE: To determine the activity of hen egg lysozyme (HEL) deposited on
      conventional and silicone hydrogel contact lens materials by using an in vitro
      model. METHODS: ACUVUE 2 (etafilcon A), PureVision (balafilcon A), ACUVUE Advance
      (galyfilcon A), Focus NIGHT & DAY (lotrafilcon A), O2 Optix (lotrafilcon B),
      Proclear (omafilcon A), and ACUVUE OASYS (senofilcon A) contact lenses were
      deposited in vitro in a phosphate-buffered solution (PBS) containing 2 mg/mL HEL.
      Lenses were briefly rinsed in PBS to remove unbound material and extracted in a
      mixture of acetonitrile and trifluoroacetic acid. After lyophilization, extracts
      were examined for lysozyme activity by micrococcal assay and total protein by
      Western blot. RESULTS: In terms of total protein accumulation, ACUVUE 2 showed
      the most, with 1,800 microg per lens. Proclear was next, with 68 microg per lens,
      and Focus NIGHT & DAY showed the least, with 2 microg per lens. ACUVUE Advance,
      ACUVUE OASYS, and O2 Optix accumulated similar amounts of lysozyme, at
      approximately 6 microg per lens. Lysozyme deposited on ACUVUE 2 showed the
      greatest activity (91% +/- 5%), and this result was statistically different from
      all other lens types (P<0.001). Lysozyme deposited on Focus NIGHT & DAY (24% +/-
      5%) and O2 Optix (23% +/- 11%) showed the lowest activity. Lysozyme deposits on
      other lens materials showed intermediate activity (ACUVUE Advance, 60% +/- 15%;
      ACUVUE OASYS, 51% +/- 9%; PureVision, 58% +/- 8%; and Proclear, 38% +/- 3%).
      CONCLUSIONS: Silicone hydrogel lenses acquire less lysozyme deposit than
      conventional group II (Proclear) or group IV (ACUVUE 2) lenses do, and the levels
      of activity of the lysozyme are highly variable between materials.

PMID- 17502749
TI  - Extended-wear silicone hydrogel soft contact lenses in the management of moderate
      to severe dry eye signs and symptoms secondary to graft-versus-host disease.
AB  - PURPOSE: To determine the safety and efficacy of the Focus NIGHT & DAY (CIBA
      Vision, Duluth, GA) silicone hydrogel contact lens in the management of
      refractory, moderate to severe dry eye signs and symptoms secondary to graft
      versus-host disease (GVHD). METHODS: Seven patients with GVHD and moderate to
      severe dry eye disease as determined by the Ocular Surface Disease Index (OSDI)
      questionnaire were fitted with a near plano Focus NIGHT & DAY soft contact lens
      (SCL) used on a 7-night continuous-wear basis. Visual acuity, objective measures
      of dry eye disease (i.e., Schirmer I, tear breakup time, and corneal fluorescein
      staining), and OSDI scores were compared before SCL wear and after 1 week and 1
      month of SCL wear. RESULTS: There was significant improvement in subjective
      assessment of dry eye symptoms (initial vs. 1-month OSDI score, 76.8 +/- 13.6 vs.
      31.2 +/- 17.8, P<0.0005, paired t test). In addition, patients had significant
      improvement in best-corrected visual acuity after 1 month of SCL wear (initial
      vs. 1-month logMAR visual acuity for the right eye, 0.23 +/- 0.050 vs. 0.04 +/-
      0.027, P<0.007; initial vs. 1-month logMAR visual acuity for the left eye, 0.22
      +/- 0.049 vs. 0.04 +/- 0.020, P<0.007, analysis of variance, Dunnett post hoc).
      There were no significant changes in results of Schirmer I testing, corneal
      fluorescein staining, or tear breakup time. No adverse events or complications of
      SCL wear were observed. CONCLUSIONS: The Focus NIGHT & DAY contact lens can
      improve subjective dry eye symptoms and visual acuity in patients with refractory
      dry eye disease secondary to GVHD.

PMID- 17502750
TI  - Does the level of available oxygen impact comfort in contact lens wear?: A review
      of the literature.
AB  - PURPOSE: Wear of low-Dk/t lenses has long been associated with signs and symptoms
      indicative of hypoxia and with patient symptoms of dryness and discomfort.
      Although patient discomfort during soft contact lens wear has been generally
      attributed to lens dehydration, research studies aimed at verifying that
      connection have been unsuccessful. With the advent of high-Dk/t silicone hydrogel
      lenses, not only have improvements in clinical signs of hypoxia been documented,
      but improvements in patient symptoms of dryness and discomfort also have been
      documented. This literature review was undertaken to examine historic and current
      literature to determine whether the level of available oxygen is associated with
      patient symptoms of dryness and discomfort. METHODS: Literature was reviewed
      related to soft contact lens dehydration, corneal hypoxia, patient symptoms of
      dryness and discomfort, and current clinical studies of silicone hydrogel lens
      wear. RESULTS: Through the years, the body of knowledge has grown supporting a
      connection between decreased levels of available oxygen to the cornea caused by
      low-Dk/t contact lens wear and negative impacts on the signs of corneal health
      and patient symptoms. CONCLUSIONS: Available published literature suggests that
      many of these changes in patient signs and symptoms seen with low-Dk/t lens wear
      may be related to an inflammatory response. Clinical studies of high-Dk/t
      silicone hydrogel lenses further support a significant connection between the
      level of available oxygen during contact lens wear and improved patient symptoms
      of comfort, including dryness.

PMID- 17502751
TI  - Comparison of central corneal thickness measured by four different pachymeters.
AB  - PURPOSE: To compare three different ultrasound pachymeters and an optical
      scanning device for measuring central corneal thickness (CCT). METHODS: This was
      a prospective study of 45 consecutive patients (90 eyes), who were seen in
      consultation for corneal refractive surgery and were tested by the same clinician
      on one visit. Thirty-five patients with no previous corneal eye surgery (group 1)
      and 10 who had undergone LASIK (group 2) were analyzed separately. Pachymetry was
      measured with the Pach V, PachPen, PachMate, and Orbscan II instruments. RESULTS:
      Generalized Estimation Equations showed significant differences between the
      Orbscan II and the ultrasound instruments (5.2-22.8 microm) in group 1 and 2, and
      between the Pach V and the PachPen or PachMate (2.3-3.8 microm) in group 1. In
      group 2, 10 of 20 eyes had a range of measurements over 20 microns. CONCLUSIONS:
      In 45 consecutive patients tested on one visit by the same clinician, CCT
      measured with three ultrasonic pachymeters, including two hand-held units, was
      clinically comparable in group 2. CCT measured with two ultrasonic pachymeters
      (i.e., PachMate and PachPen) was clinically comparable in group 1. The Orbscan II
      data differ from the other three instruments in both groups but more in the
      patients who had undergone LASIK (group 2).

PMID- 17502752
TI  - Comparative minimal inhibitory and mutant prevention drug concentrations of four
      fluoroquinolones against ocular isolates of Haemophilus influenzae.
AB  - PURPOSE: Haemophilus influenzae is a known ocular pathogen, particularly in the
      pediatric population. The purpose of this study was to determine the minimal
      inhibitory concentration (MIC) and mutant prevention concentration (MPC) values
      of third-generation (i.e., ciprofloxacin and ofloxacin) and fourth-generation
      (i.e., gatifloxacin and moxifloxacin) fluoroquinolone antibiotics against
      clinical ocular isolates of H. influenzae. METHODS: Twenty-six clinical isolates
      of H. influenzae were evaluated. For MIC testing, approximately 10(5) colony
      forming units/mL of test organism was added to an H. influenzae test medium
      containing twofold dilution increments of each fluoroquinolone. Cultures were
      incubated for 18 to 24 hours at 35 degrees C to 37 degrees C in 5% CO2. The
      lowest drug concentration that prevented growth was recorded as the MIC. The
      lowest drug concentration that inhibited 90% of strains tested was recorded as
      the MIC90. To determine MPC values, more than 10(10) bacteria were inoculated to
      agar plates containing varying drug concentrations and incubated for 24 to 48
      hours at 35 degrees C to 37 degrees C in 5% CO2. To confirm MPC values, bacteria
      isolated from drug-containing plates were subcultured to drug-free agar,
      incubated, and then subcultured to a plate with the same drug concentration. The
      lowest drug concentration that allowed no growth was recorded as the MPC.
      RESULTS: All tested fluoroquinolones were highly active against H. influenzae.
      The MIC90 values were 0.016 microg/mL for gatifloxacin and ciprofloxacin and
      0.031 microg/mL for moxifloxacin and ofloxacin. The MPC90 values were 0.125
      microg/mL for gatifloxacin and 0.5 microg/mL for moxifloxacin, ofloxacin, and
      ciprofloxacin. CONCLUSIONS: All evaluated fluoroquinolones were effective against
      H. influenzae. The MIC90 and MPC90 values for gatifloxacin were consistently
      lower than those for moxifloxacin.

PMID- 17502753
TI  - The metabolic syndrome, the Guy syndrome and the hypofit syndrome.

PMID- 17502754
TI  - 'Il buso' (the orifice). How much did Leonardo know of the aortic valve?

PMID- 17502755
TI  - Pathogenesis, management, and prevention of recurrent pericarditis.
AB  - Recurrent pericarditis is one of the most troublesome complications of acute
      pericarditis and, despite recent advances, remains one of the most challenging
      problems in pericardial diseases. The exact recurrence rate is unknown, but a
      reasonable estimate is 30%. The diagnosis is based on clinical criteria, and only
      routine laboratory testing is required. In many, probably most cases, this is an
      autoimmune disease, but sometimes it is caused by reactivation of viral
      pericarditis, an unrelated infection, or is provoked by corticosteroid therapy.
      Therapeutic modalities are non-specific and varied, and usually the etiology is
      autoimmunity. Non-steroidal anti-inflammatory drugs with the possible addition of
      colchicine are the best first-choice treatment, before steroid therapy is tried.
      Corticosteroid therapy is an independent risk factor for recurrences. In order to
      provide an evidence-based clinical approach to management, we performed a
      systematic review of all publications on acute and recurrent pericarditis
      focusing on recent clinical trials.

PMID- 17502756
TI  - The Coanda effect in cardiology.
AB  - Many of the current technologies used today in clinical practice owe their lives
      to physicians. Coanda effect was originally described by the romanian scientist
      as a phenomenon with application in aerodynamics, the main field of interest for
      Henri Coanda. He made the observation that a thin liquid jet, passing through a
      narrow channel which is followed by a curved surface, deviates according to the
      surface' shape, adhering to it. The description of the phenomenon and a possible
      explanation was found in a patent registrated in France, in 1934. It is
      interesting how a physical phenomenon described 70 years ago has found its clear
      demonstration and real time visualization on color Doppler flow mapping. Coanda
      effect influences jet size and color encoding, determining (for eccentric jets)
      smaller color Doppler jet areas, greater variance and reverse velocity encoding.
      The phenomenon may alter the interpretation of color Doppler images and needs to
      be taken into account for an appropriate echocardiography assessment of valvular
      regurgitation and other abnormal flows.

PMID- 17502757
TI  - Is it possible to create a linear lesion with no local electrograms? Comparison
      between a three-dimensional mapping system and conventional fluoroscopy for
      cavotricuspid isthmus ablation of typical atrial flutter.
AB  - OBJECTIVE: The aim of this prospective, randomised study was to evaluate the
      efficacy, safety and long-term outcomes of the complete disappearance of local
      electrograms along the linear lesion using the EnSite NavX three-dimensional
      mapping system as compared with conventional fluoroscopy for ablation of typical
      atrial flutter (AFL). METHODS: Seventy-three patients with spontaneous AFL
      episodes were randomised to undergo fluoroscopy-guided (group I, n=35) or EnSite
      NavX-guided (group II, n=38) ablation. When bidirectional isthmus block was
      achieved, the catheter was navigated back along the ablation line to assess the
      presence of local potentials along the lesion line. RESULTS: Bidirectional
      isthmus block was achieved in all patients. Mean total fluoroscopy time was 19.8
      +/- 4.1 min in group I and 9.1 +/- 3.5 min in group II (P<0.001); mean
      fluoroscopy time required for radiofrequency ablation was 6.9 +/- 1.4 min in
      group I and 0.6 +/- 0.3 min in group II (P<0.001). During a follow-up of 16 +/- 9
      months, three patients in group I (10%) experienced recurrence of AFL as opposed
      to none in group II (P<0.005). CONCLUSIONS: NavX technology allows accurate re
      navigation of the lesion line to assess the presence of local potentials during
      an ablation procedure for typical AFL. Electroanatomic activation mapping can
      accurately identify gaps in the linear radiofrequency lesion with no AFL
      recurrence compared with 20% of recurrences after a standard procedure.

PMID- 17502758
TI  - Prevalence, predictors and prognostic value of acute impairment in renal function
      during intensive unloading therapy in a community population hospitalized for
      decompensated heart failure.
AB  - BACKGROUND AND METHODS: Chronic heart failure (CHF) is often associated with
      impaired renal function. Diuretics and vasodilators may lead to aggravated renal
      dysfunction (ARD), particularly among patients with decompensated CHF. Although
      the prevalence of ARD has been evaluated in patients awaiting heart
      transplantation, little is known about ARD in the community sample of CHF
      patients. Accordingly, we prospectively assessed the prevalence, predictors and
      prognostic value of ARD in 79 consecutive patients admitted to our general
      community hospital for decompensated CHF undergoing intensive unloading therapy
      (intravenous nitroprusside and furosemide). ARD was defined as a >or= 25%
      increase in serum creatinine between admission and maximal value of >or= 2 mg/dl.
      RESULTS: Sixteen patients (20%) developed ARD with a mean increase in serum
      creatinine of 31% (from 1.74 +/- 0.6 to 2.27 +/- 0.9 mg/dl). ARD persisted at 8
      day evaluation in seven of 16 subjects (44%) whereas it was reversible in nine
      (56%). Lower creatinine clearance at baseline [exp beta = 0.93, 95% confidence
      interval (CI)=0.87-0.99] and the higher dose of furosemide (exp beta=1.02, 95%
      CI=1.01-1.03) emerged as independent predictors of ARD. During a follow-up of 11
      +/- 8 months, death and hospitalization for worsening CHF occurred more
      frequently in ARD than non-ARD patients (69% versus 17%, P=0.0001; 69% versus
      29%, P=0.003, respectively). Persistent ARD was a powerful independent predictor
      of long-term adverse outcome (odds ratio=11.1; 95% CI=1.12-36.1; P=0.04).
      CONCLUSIONS: Intensive unloading therapy is associated with the development of
      ARD in one-fifth of the community population hospitalized for decompensated CHF.
      The magnitude of this phenomenon is not greater than that observed in younger
      selected populations with advanced CHF, and depends on baseline renal function
      and increased diuretic dosage. ARD persisting after 8 days from starting
      intensive unloading is a powerful predictor of subsequent worsened clinical
      outcome.

PMID- 17502759
TI  - Aortic dimensions in Turner's syndrome: two-dimensional echocardiography versus
      magnetic resonance imaging.
AB  - BACKGROUND: Patients with Turner's syndrome have an increased risk of cardiac
      death caused by aortic disease. Consensus has not been reached about the best
      method to image the aorta in this syndrome. AIM: This present study aimed: (i) to
      evaluate thoracic and abdominal aortic dimensions by two-dimensional echo (2-DE)
      and magnetic resonance imaging (MRI) and (ii) to assess agreement between 2-DE
      and MRI measurements. MATERIAL AND METHODS: Among 75 kariotypically proven
      Turner's syndrome patients, 59 (79%) (mean age: 22 +/- 7 years) underwent a 2-DE
      and an MRI study of the thoracic and proximal abdominal aorta. The aortic root
      (AR), the sino-tubular aortic junction (STJ), the first part of the ascending
      thoracic aorta (AscTA), the aortic arch (AArch), the descending thoracic aorta
      (DTAp) a few centimetres below the isthmus and the abdominal aorta (AbA) were
      analysed. The Bland and Altman method and Lin's concordance correlation
      coefficient were utilized to compare 2-DE and MRI aortic dimensions. RESULTS:
      Compared to MRI, feasibility of aortic imaging by 2-DE was identical at AR level,
      but lower when measuring distal aorta (88% at DTAp and 91.5% at AbA level versus
      100%). The 2-DE and MRI showed a very slight difference between measurements and
      a high concordance correlation coefficient at the level of AR and AscTA;
      correlations were weaker at the other aortic levels. Absolute differences
      calculated at each measurement level showed that concordance (defined as
      differences within 1 mm between 2-DE and MRI absolute measures) was highest at AR
      (45.6%) and AscTA (28%) level and lowest at STJ (12.2%) level. The 2-DE
      overestimated aortic arch diameters in approximately 70% of cases, whereas at the
      remaining aortic levels MRI measurements were usually 1 mm higher compared to the
      corresponding 2-DE values. CONCLUSIONS: Concordance between 2-DE and MRI was
      found to be very good at the AR and AscTA levels. Because the risk of aortic
      complication is higher when AR and proximal thoracic aorta are dilated, 2-DE may
      be considered a useful method to screen for aortic disease and a good choice to
      follow proximal aortic dimensions over time in Turner's syndrome patients.

PMID- 17502760
TI  - Does 16-slice multidetector computed tomography improve stent patency and in
      stent restenosis evaluation?
AB  - AIM: To assess the value of multidetector computed tomography (MDCT) in the non
      invasive evaluation of stents. METHODS: We studied 88 patients (142 stents): 48
      with 1.2-mm MDCT, 40 with 0.6-mm MDCT considering accuracy in assessing the
      vessel lumen, stent patency and intra-stent restenosis. Coronary angiography
      comprised the gold standard. RESULTS: Occlusion was detected, respectively, in
      three of 72 versus four of 70 cases. Patency was assessed in all cases. In-stent
      restenosis was diagnosed in two of eight cases with thin-slice MDCT. CONCLUSIONS:
      0.6-mm MDCT allows a better visualization of stent lumen and in-stent restenosis
      versus 1.2-mm MDCT.

PMID- 17502761
TI  - Relationships of the appropriateness of left ventricular mass to left atrial size
      and function in arterial hypertension.
AB  - OBJECTIVE: To investigate whether left ventricular mass (LVM) appropriateness may
      be related to left atrial changes in both size and performance in arterial
      hypertension. METHODS: Three hundred and thirty-five hypertensive outpatients
      were studied by Doppler echocardiography and divided into two groups on the basis
      of LVM appropriateness. Left ventricular mass was defined inappropriate when
      greater than 128% of the value predicted from age, sex and stroke work (95th
      percentile of normal distribution) and appropriate for values <or= 128%. Left
      atrial volumes were obtained by two-dimensional echocardiography, left atrial
      ejection force was used as an index of systolic performance and calculated
      accordingly with Manning's formula. RESULTS: Left ventricular mass was
      inappropriate in 58 patients (17%). Individuals with an inappropriate mass showed
      higher left atrial maximum and minimum volumes compared to those with appropriate
      mass (all P<0.001), independent of left ventricular geometry. Left atrial
      ejection fraction (44 +/- 13 versus 46 +/- 13%) and ejection force (8.4 +/- 4.8
      versus 9.3 +/- 5.3 kdynes) were not statistically different between groups. In
      the whole group, left atrial volumes and stroke volume showed a close positive
      relationship with respect to crude values of LVM and inappropriate LVM, whereas
      left atrial ejection force was better related to left ventricular concentric
      geometry. This correlation was explained by the more pronounced diastolic
      dysfunction found in the highest quartile of left atrial ejection force.
      CONCLUSIONS: In arterial hypertension, left atrial enlargement parallels an
      increase in LVM. Left atrial ejection force is at least in part independent of
      this mechanism, being mainly linked to concentric geometry and left ventricular
      diastolic function impairment.

PMID- 17502762
TI  - The early anti-oxidant effect of carvedilol predicts the clinical course in
      congestive heart failure patients.
AB  - BACKGROUND: Carvedilol, a beta1 and beta2 as well as an alpha1 adrenoreceptor
      antagonist with multiple hemodynamic, anti-ischemic and anti-oxidant properties,
      is widely accepted for the treatment of hypertension and congestive heart failure
      (CHF). It has been shown to improve morbidity and mortality in CHF. OBJECTIVES:
      To assess whether the anti-oxidant effect of carvedilol has an impact on the
      clinical course in post-myocardial infarction (MI) CHF. METHODS: Thirty-nine
      recent MI patients, aged 60.5 +/- 7 years, New York Heart Association functional
      class (FC) II-III, and left ventricular ejection fraction (LVEF) 29 +/- 3.8%,
      underwent oxygen free radical (OFR) assessment using the thiobarbituric acid
      reactive substances, thermochemoluminescence and conjugated dienes methods. OFR
      was determined at baseline, 1, 3, 12, and 24 h after 3.125, 6.25 and 12.5 mg
      carvedilol, and after 6 months of treatment. Brain natriuretic peptide (BNP),
      LVEF, FC change, 6-min walk test (6MW) and quality of life scores were evaluated
      before and after 6 months. RESULTS: Two patterns of OFR activity were found. In
      29 patients (group 1) a significant and consistent reduction in OFR following
      administration of each dose of carvedilol was found, significantly correlating
      with each of the outcome parameters. In ten patients (group 2), no change in OFR
      was found, nor in any of the other outcomes. At 6 months, FC improved in 23
      patients from group 1 (79.3%) and only in one (10%) from group 2 (P<0.01). 6MW
      increased by more than 10% in group 1 with no change in group 2 (P<0.05). BNP
      decreased from 397 +/- 36 pg/ml to 171 +/- 15.9 pg/ml (P<0.01) in group 1
      compared to 381 +/- 32.5 pg/ml and 405 +/- 36 pg/ml, respectively (P=not
      significant) in group 2. One year hospital admissions and death rate were
      significantly higher in group 2. CONCLUSIONS: The early anti-oxidative effect of
      carvedilol correlates well with the clinical course and probably predicts it.

PMID- 17502763
TI  - Non-Q-wave myocardial infarction associated with three-vessel thrombosis.
AB  - Acute coronary syndromes have been traditionally considered the consequence of
      the rupture of a single plaque. Recent evidence has suggested that this is not
      the case, and intravascular ultrasound studies have demonstrated that an average
      of two to three ruptured plaques are present in patients admitted to hospital for
      unstable angina or infarction. We present a case of three-vessel occlusive
      thrombosis causing non-Q-wave myocardial infarction treated successfully with IIb
      IIIa inhibitors.

PMID- 17502764
TI  - Successful radiofrequency ablation of atrial tachycardias in surgically repaired
      Ebstein's anomaly using the Carto XP system and the QwikStar catheter.
AB  - We describe the case of a child with three different atrial tachyarrhythmias
      originating from the right atrium, in whom a limited modified maze procedure was
      performed during surgical repair of an Ebstein's anomaly. Successful
      radiofrequency transcatheter ablation of all atrial tachyarrhythmias, one re
      entrant and two focal, was obtained using the Carto XP EP three-dimensional
      navigation and ablation system, the new QwikMap software technology and the new
      mapping/ablation QwikStar multipolar catheter. No conventional mapping was used
      in addition to the three-dimensional system. Total procedural time was about 3 h
      and fluoroscopy time was 40 min. There were neither recurrences of the
      tachycardias nor complications during the follow-up (15 months).

PMID- 17502765
TI  - Hypertrophic cardiomyopathy in a patient with Down's syndrome.
AB  - In persons with Down's syndrome (DS), congenital cardiac defects are frequent,
      including atrioventricular canal defect, ventricular septal defects and atrial
      septal defects. However, in patients with this syndrome, hypertrophic
      cardiomyopathy is very rare because only five cases have been previously reported
      in the literature. We have identified one male 52-year-old with DS and non
      obstructive cardiomyopathy. The echocardiogram of this patient showed a prevalent
      apical involvement of the left ventricular hypertrophy as previously reported in
      two adult patients with DS and hypertrophic cardiomyopathy. Although rare,
      hypertrophic cardiomyopathy can occur in individuals with DS and, in adult
      patients, the apical form is frequent.

PMID- 17502766
TI  - Marked left ventricular hypertrophy mimicking hypertrophic cardiomyopathy
      associated with steroid therapy for congenital adrenal hyperplasia.
AB  - We describe a child treated with high-dose steroid therapy for congenital adrenal
      hyperplasia who showed marked left ventricular hypertrophy mimicking hypertrophic
      cardiomyopathy associated with steroid therapy for congenital adrenal
      hyperplasia. Cardiomyopathy reversed completely when an appropriate steroid
      therapeutic regimen was established.

PMID- 17502767
TI  - Progressive myocardial scarring from sarcoidosis.

PMID- 17502768
TI  - Transcatheter closure of ruptured sinus of Valsalva aneurysm causing Fontan
      circulation failure.
AB  - Congenital sinus of Valsalva aneurysm is a rare cardiac malformation that usually
      becomes symptomatic as a consequence of intracardiac or extracardiac rupture. It
      is difficult to suspect in association with complex cardiac defects and its
      rupture may be misdiagnosed as progressive aortic regurgitation. This case report
      refers to a patient with tricuspid atresia submitted to Fontan procedure five
      years previously, in whom a sinus of Valsalva aneurysm rupture into the accessory
      ventricular chamber caused rapidly progressive heart failure. The malformation
      was suspected by echocardiography and treated by percutaneous implantation of an
      Amplatzer duct occluder, with immediate improvement of the patient's clinical and
      functional status.

PMID- 17502769
TI  - The crucial role of the therapeutic window in understanding the clinical
      relevance of the poor versus the ultrarapid metabolizer phenotypes in subjects
      taking drugs metabolized by CYP2D6 or CYP2C19.

PMID- 17502770
TI  - Association of clozapine-induced weight gain with a polymorphism in the leptin
      promoter region in patients with chronic schizophrenia in a Chinese population.
AB  - Weight gain is a problem commonly encountered with antipsychotic treatment and
      has become more apparent with increasing use of the newer atypical
      antipsychotics. The adipocyte-derived hormone, leptin, has been associated with
      body weight and energy homeostasis, and abnormal regulation of leptin could play
      a role in weight gain induced by antipsychotics. We investigated whether a leptin
      gene promoter variant affected weight gain after long-term treatment with
      clozapine in chronic schizophrenia. Leptin G2548A polymorphism was genotyped in
      102 Chinese Han inpatients with chronic schizophrenia treated with clozapine.
      Weight gains, expressed as change in body mass index (BMI), were monitored after
      long-term clozapine treatment. We found a significant relationship between the 3
      leptin G/A genotypes and mean BMI gain (F(2,99) = 3.35, P = 0.039, r(2) = 0.09).
      Moreover, genotype had a strong effect on BMI gain in male (P = 0.004, r(2) =
      0.16), but not in female patients (P > 0.05). Thus, variation in the leptin gene
      may be a risk factor for weight gain in male patients with schizophrenia on long
      term clozapine treatment.

PMID- 17502771
TI  - All-cause treatment discontinuation in schizophrenia during treatment with
      olanzapine relative to other antipsychotics: an integrated analysis.
AB  - OBJECTIVES: Treatment continuation, as measured by time to all-cause treatment
      discontinuation, is a broad measure of overall treatment effectiveness. This
      integrated analysis compared the likelihood of discontinuation from olanzapine
      treatment versus other antipsychotics among patients with schizophrenia. METHODS:
      Clinical trials of all sponsors were included if they met the following criteria:
      double-blind, randomized, comparative; duration of 12 weeks or longer; no
      mandatory discontinuation before 12 weeks; and schizophrenia-spectrum disorders;
      20 patients or more per treatment. Weighted mean hazard ratios and 95% confidence
      intervals were calculated from discontinuation time. Meta-analyses were performed
      for the following comparators that had at least 2 studies: haloperidol (5
      studies), risperidone (5 studies), ziprasidone (2 studies), clozapine (3
      studies), and perphenazine (2 studies) (13 studies in total; 3 included more than
      1 comparator). Only 1 eligible published study was found for fluphenazine,
      amisulpride, and quetiapine; therefore, meta-analyses could not be performed for
      these comparators. RESULTS: Significantly (P < 0.05) greater likelihood of
      discontinuation relative to olanzapine treatment (hazard ratio [95% confidence
      interval]) was observed for haloperidol (1.4 [1.2-1.7]), risperidone (1.3 [1.1
      1.6]), ziprasidone (1.6 [1.4-2.0]), and quetiapine (1.4 [1.1-1.9]), but not
      clozapine (1.2 [0.9-1.6]), fluphenazine (1.8 [0.8-4.3]), perphenazine (1.3 [0.7
      2.1]), or amisulpride (1.1 [0.8-1.6]). CONCLUSIONS: These data suggest that
      patients with schizophrenia and related disorders may continue olanzapine
      treatment longer than haloperidol, risperidone, ziprasidone, or quetiapine
      treatment.

PMID- 17502772
TI  - Selective serotonin reuptake inhibitors and risk of acute pancreatitis: a
      population-based case-control study.
AB  - To examine whether use of selective serotonin reuptake inhibitors (SSRIs) is
      associated with acute pancreatitis, a population-based case-control study was
      conducted in the counties of North Jutland (data 1991-2003), Aarhus (data 1996
      2003), and Viborg (data 1998-2003), Denmark. Through hospital discharge
      registries, we identified all patients with an incident hospitalization of acute
      pancreatitis. From the Civil Registration System, we selected 10 sex- and age
      matched population controls per case using risk set sampling. All prescriptions
      of SSRI and other antidepressant drugs within 90 days (present users) or 91 to
      365 days (former users) before admission with acute pancreatitis, or index date
      among controls, were collected from prescription databases. First-time users were
      defined as those who redeemed their first SSRI prescription within 14 days before
      admission/index date. We estimated the relative risk of acute pancreatitis after
      exposure to SSRI or other antidepressants, adjusting for potential confounders.
      We included 3083 cases of acute pancreatitis and 30,830 controls. The adjusted
      odds ratio (OR) for acute pancreatitis in present users of SSRI was 1.2 (95%
      confidence interval [CI], 1.0-1.5); for former users, the adjusted OR was 1.2
      (95% CI, 0.9-1.7). For current and former users of other antidepressant drugs,
      the corresponding adjusted ORs were 1.4 (95% CI, 1.1-1.7) and 1.4 (95% CI, 1.0
      1.9), respectively. The adjusted OR of acute pancreatitis in first-time users of
      SSRI was 2.8 (95% CI, 1.1-7.0). We found use of SSRIs to be associated with
      increased risk for acute pancreatitis. However, the estimate did not differ
      between present or former users of SSRI and was not materially different from the
      estimate in users of other antidepressant drugs. Therefore, our data suggest that
      the increased risk is related to confounding by lifestyle factors or the
      underlying depression.

PMID- 17502773
TI  - The role of anticonvulsant drugs in anxiety disorders: a critical review of the
      evidence.
AB  - Antiepileptic drugs (AEDs) have been successfully used in the treatment of mood
      disturbances, leading clinicians and researchers to investigate their use in
      other psychiatric disorders. This article reviews the literature about the
      potential efficacy of AEDs in anxiety disorders. An updated MEDLINE search
      (January 1970 to September 2006) using the terms "panic disorder," "agoraphobia,"
      "posttraumatic stress disorder," "obsessive-compulsive disorder," "generalized
      anxiety disorder," "social phobia," "phobia," "carbamazepine," "phenobarbital,"
      "phenytoin," "valproate," "lamotrigine," "topiramate," "vigabatrin," "tiagabine,"
      "gabapentin," "levetiracetam," and "pregabalin" showed more than 70 articles and
      38 published studies. Only articles published in English were reviewed. We have
      assigned level 1 of evidence to meta-analysis and replicated randomized
      controlled trials, level 2 to at least 1 randomized controlled trial, level 3 to
      uncontrolled trials with 10 or more subjects, and level 4 to anecdotal case
      reports. The strongest evidence has been demonstrated for pregabalin in social
      phobia and generalized anxiety disorder, lamotrigine in posttraumatic stress
      disorder, and gabapentin in social anxiety. The available data about gabapentin
      in panic disorder are somewhat mixed, and more definitive conclusion would
      require additional studies. This review suggests that AEDs can be an alternative
      treatment in some anxiety disorders. Further investigation is needed to determine
      in what circumstances they should be used in individuals who are partially
      responsive or nonresponsive to conventional therapy.

PMID- 17502774
TI  - Increased (R)-methadone plasma concentrations by quetiapine in cytochrome P450s
      and ABCB1 genotyped patients.
AB  - Steady-state plasma concentrations of (R)- (ie, the active form), (S)-, and (R,S)
      methadone were measured in 14 addict patients in methadone maintenance treatment,
      before and after introduction of quetiapine, administered at a mean dosage of 138
      mg/d (SD, 87 mg/d; median, 125 mg/d; range, 50-300 mg/d) during a mean period of
      30 days (SD, 8 days; median, 30 days; range, 20-48 days). Eleven patients were
      genotyped as being CYP2D6 extensive metabolizers (EMs) and 3 patients as poor
      metabolizers. Eleven patients had the ABCB1 3435 CT or CC genotypes, and 3
      patients had the ABCB1 3435 TT genotype, the latter genotype being associated
      with lower P-glycoprotein activity. Quetiapine significantly increases (R)
      methadone concentration-dose ratios in the whole group [increase for (R)
      methadone: mean, +21%; SD, +28%; median, +13%; range, -23% to +85%; P = 0.026],
      but not for (S)-methadone (mean, +23%; SD, +43%; median, +6%; range, -30% to
      +115%; P = 0.12) or for (R,S)-methadone (mean, +21%; SD, +34%; median, +9%;
      range, -21% to +95%; P = 0.064). The mean increases of (R)-methadone
      concentration-dose ratios were of 7%, 21%, and 30% in the CYP2D6 poor
      metabolizers, heterozygous EMs, and homozygous EMs, respectively, whereas they
      were of 3%, 23%, and 33% in the subjects with the ABCB1 3435 TT, CT, and CC
      genotypes, respectively. Thus, quetiapine increases the plasma concentrations of
      (R)-methadone, possibly in part by an interaction with CYP2D6 and/or with the P
      glycoprotein transporter system. No signs of overmedication caused by increased
      methadone plasma concentrations were noticed by the staff or reported by the
      patients.

PMID- 17502775
TI  - Pharmacokinetics of aripiprazole and concomitant carbamazepine.
AB  - The objective of this study was to assess the pharmacokinetics of aripiprazole
      when coadministered with carbamazepine using an open-label sequential treatment
      design in patients with schizophrenia or schizoaffective disorder. Nine male
      patients were enrolled and received aripiprazole monotherapy (30 mg once daily)
      for 14 days, after which aripiprazole steady-state pharmacokinetics were
      assessed. Subjects were then administered carbamazepine together with
      aripiprazole for 4 to 6 weeks. The dose of carbamazepine was titrated to produce
      a trough serum concentration within the range of 8 to 12 mg/L. Aripiprazole
      pharmacokinetics were then assessed in the presence of carbamazepine. Six
      patients completed the study as designed. Coadministration with carbamazepine
      decreased the values of mean peak plasma concentration and area under the plasma
      concentration-time curve of aripiprazole by 66% and 71%, respectively (P = 0.001
      and 0.002, respectively). Similarly, coadministration with carbamazepine
      decreased the values of mean peak plasma concentration and area under the plasma
      concentration-time curve over the 24-hour dosing interval of the major active
      metabolite of aripiprazole, dehydroaripiprazole, by 68% and 69%, respectively (P
      < 0.001). Both aripiprazole and dehydroaripiprazole are substrates for the
      cytochrome P-450 3A4 enzyme which is known to be induced by carbamazepine dosed
      to steady state. Thus, therapeutic doses of carbamazepine had significant effects
      on the pharmacokinetics of aripiprazole in patients with schizophrenia or
      schizoaffective disorder. When carbamazepine is added to aripiprazole therapy,
      aripiprazole dose should be doubled (to 20-30 mg/d). Additional dose increases
      should be based on clinical evaluation. When carbamazepine is withdrawn from
      combination therapy, aripiprazole dose should then be reduced.

PMID- 17502776
TI  - Neuroleptic treatment effect on mitochondrial electron transport chain:
      peripheral blood mononuclear cells analysis in psychotic patients.
AB  - A limitation in the use of classic neuroleptic drugs is the eventual appearance
      of extrapyramidal symptoms. Some studies, mainly based on experimental
      situations, have related these symptoms with a defect in the mitochondrial
      electron transport chain (ETC), especially with complex I (CI). One of the
      advantages of the "atypical" neuroleptics is a lower incidence of movement
      disorders. We studied peripheral blood mononuclear cells from naive schizophrenic
      patients (n = 25) and patients under chronic treatment with 1 "typical"
      neuroleptic (haloperidol, n = 15) or 1 "atypical" neuroleptic (risperidone, n =
      23; or clozapine, n = 21). Patients were on standard clinical situation, on
      treatment for at least 28 months, and did not present signs or symptoms of
      extrapyramidal dysfunction. Absolute enzyme activities of ETC complexes I to IV
      were spectrophotometrically quantified, and oxygen consumption with substrates of
      different complexes was measured polarographically. As an indirect measure of
      oxidative damage, we quantified membrane lipid peroxidation through the loss of
      cis-parinaric acid fluorescence. We found differences among groups when comparing
      the activity of CI, which was decreased in patients receiving neuroleptics,
      either assessed enzymatically or through oxygen consumption. This effect was
      lower for atypical neuroleptics than for haloperidol. Haloperidol was also
      associated with a significant increase of peripheral blood mononuclear cell
      membrane peroxidation. We conclude that antipsychotics given at clinical standard
      doses, either typical or atypical, inhibit CI of the ETC. It remains to be
      established if this finding in a nontarget tissue for antipsychotics may account
      for the lower incidence of movement disorders observed in patients on atypical
      agents.

PMID- 17502777
TI  - The effectiveness of intramuscular biperiden in acute akathisia: a double-blind,
      randomized, placebo-controlled study.
AB  - Neuroleptic-induced acute akathisia (NIA) is a distressing condition and an
      important clinical problem because it is associated with treatment noncompliance
      and suicidal or impulsive behavior. Anticholinergics are among the treatment
      options; however, a review of the literature fails to identify a double-blind,
      randomized, placebo-controlled study of these medications in NIA. In a
      randomized, double-blind, placebo-controlled design, we studied the effectiveness
      of intramuscular biperiden (n = 15) or isotonic saline (n = 15) in the treatment
      of NIA diagnosed with the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition criteria. Injections were repeated up to 3 times unless akathisia
      was completely treated (scored 0 for global akathisia with the Barnes Akathisia
      Rating Scale). Patients were assessed for akathisia, other movement disorders,
      and psychiatric symptoms at baseline and 3 times after the first injection at 2
      hour intervals. Response was defined as at least a 2-point decline in the global
      akathisia score. The numbers of responders in the 2 groups were not significantly
      different (7 and 5 in the biperiden and placebo groups, respectively). The
      courses of individual items on the Barnes Akathisia Rating Scale were also
      similar. Our results suggest that intramuscular biperiden should not be
      considered as a first-line treatment of NIA.

PMID- 17502778
TI  - Relevance of exclusion criteria in antidepressant clinical trials: a replication
      study.
AB  - INTRODUCTION: Patients in clinical randomized controlled trials (RCTs) of
      antidepressants are different from those typically treated in clinical practice,
      which may affect the generalizability of data from RCTs. We attempted to
      replicate the work of Zimmerman and colleagues (Zimmerman M, Mattia JI, Posternak
      MA. Are subjects in phamacological treatment trials of depression representative
      of patients in routine clinical practice? Am J Psychiatry. 2002;159:469-473),
      demonstrating that most patients seeking clinical treatment of depression would
      not qualify for an RCT based on common exclusion criteria. METHODS: Eight hundred
      seventeen patients presenting to an outpatient private practice were evaluated by
      retrospective chart review. The 11 exclusion criteria outlined in the previous
      study were applied to a sample of 348 depressed adults to determine the
      percentage that would have qualified for an RCT. RESULTS: We have closely
      replicated the study of Zimmerman et al, finding that 91% of our sample would not
      qualify for an RCT based on presence of any of the 11 exclusion criteria.
      Prevalence of 7 criteria applied were found significantly different in our
      population when compared with the study of Zimmerman et al, yet exclusion rates
      came within 0.2%. When only the 5 most common criteria were applied, exclusion
      rates remained high. CONCLUSIONS: Some exclusion criteria are essential for
      ethical or diagnostic purposes or to reduce heterogeneity; others are somewhat
      arbitrary, widening the gap between research and clinical practice. Ninety-one
      percent of patients presenting for treatment of depression would not qualify for
      RCTs if the 11 exclusion criteria identified were applied; if a standard severity
      cutoff score and 4 criteria considered relevant to safety or diagnostic validity
      were used, nearly 75% would not qualify. Use of antidepressants in a typical
      clinical population is an extrapolation from research data.

PMID- 17502779
TI  - Hypophosphatemia and neuroleptic malignant syndrome.

PMID- 17502781
TI  - Aripiprazole augmentation for treatment-resistant bipolar depression: sustained
      remission after 36 months.

PMID- 17502780
TI  - Late-onset neuroleptic malignant syndrome in a patient using olanzapine.

PMID- 17502782
TI  - Aripiprazole-induced obsessive-compulsive disorder: a report of 2 cases.

PMID- 17502783
TI  - Pharmacokinetics study for hyperprolactinemia among schizophrenics switched from
      risperidone to risperidone long-acting injection.

PMID- 17502784
TI  - Low serum concentrations of reboxetine in 2 patients treated with CYP3A4
      inducers.

PMID- 17502785
TI  - Sexual disorders in subjects treated for mood and anxiety diseases.

PMID- 17502786
TI  - Duloxetine in the treatment of social anxiety disorder.

PMID- 17502787
TI  - Treatment-resistant depression: response to low-dose transdermal but not oral
      selegiline.

PMID- 17502788
TI  - Recurrent hyponatremia after substitution of citalopram with duloxetine.

PMID- 17502789
TI  - Clomipramine-induced mood and perceived performance changes in selected healthy
      individuals.

PMID- 17502790
TI  - Psychosis with sibutramine.

PMID- 17502791
TI  - Glutamate antagonists seem to be slightly effective in psychopharmacologic
      treatment of autism.

PMID- 17502793
TI  - Open trials in psychiatry: comments on article by Uchida et Al.

PMID- 17502794
TI  - Baclofen suppresses alcohol intake and craving for alcohol in a schizophrenic
      alcohol-dependent patient: a case report.

PMID- 17502795
TI  - Preventing postpartum complications in the depressed pregnant women.

PMID- 17502796
TI  - Comments on "postpartum depression" article by Dr Wisner and colleagues.

PMID- 17502798
TI  - Selective serotonin reuptake inhibitors in adolescent depression still
      controversial.

PMID- 17502800
TI  - The role of intense affective states in signaling a suicide crisis.
AB  - We explore the extent to which intense affective states in depressed patients may
      signal a suicide crisis, i.e., an acute risk for suicide. Therapists for 36
      patients who died by suicide while in treatment completed questionnaires and
      wrote detailed structured narratives. Nine affects--desperation, hopelessness,
      rage, anxiety, feelings of abandonment, loneliness, guilt, humiliation, and self
      hatred were evaluated as to their intensity in the patient before the suicide.
      Comparable information was obtained on 26 depressed, nonsuicidal patients treated
      by the same therapists. The suicide patients had a significantly greater number
      of intense affects than did the comparison patients. The affect that most
      distinguished the 2 groups was desperation, which was intense in 30 (83%) of the
      suicide patients but in none of the comparison patients. Recognizing intense
      affective states and the interaction among them may help clinicians identify a
      suicide crisis in depressed patients.

PMID- 17502802
TI  - Transcranial magnetic stimulation reduces pain in patients with major depression:
      a sham-controlled study.
AB  - This study evaluated the change in reported pain in patients with medication
      resistant major depression receiving transcranial magnetic stimulation (TMS)
      compared with sham stimulation. In this study, 68 subjects with major depression
      were randomized to either TMS or sham stimulation. Repetitive TMS was delivered
      to the left dorsolateral prefrontal cortex at a frequency of 10 Hz in 5-second
      trains at 110% of the estimated prefrontal cortex threshold. The level of pain
      was assessed before, during, and after treatment using the Systematic Assessment
      for Treatment Emergent Effects (SAFTEE) item for pain in the muscles, bones, and
      joints. Compared with sham, TMS was associated with a significant (p < 0.05)
      reduction in the SAFTEE pain item during the study. The reduction in pain could
      not be explained by the antidepressant effects.

PMID- 17502801
TI  - Smoking and suicidal behaviors in the National Comorbidity Survey: Replication.
AB  - Controversy exists about the role of mental disorders in the consistently
      documented association between smoking and suicidal behavior. This controversy is
      addressed here with data from the nationally representative National Comorbidity
      Survey-Replication (NCS-R). Assessments were made of 12-month smoking, suicidal
      behaviors (ideation, plans, attempts), and DSM-IV disorders (anxiety, mood,
      impulse-control, and substance use disorders). Statistically significant odds
      ratios (2.9-3.1) were found between 12-month smoking and 12-month suicidal
      behaviors. However, the associations of smoking with the outcomes became
      insignificant with controls for DSM-IV mental disorders. Although clear
      adjudication among contending hypotheses about causal mechanisms cannot be made
      from the cross-sectional NCS-R data, the results make it clear that future
      research on smoking and suicidal behaviors should focus more centrally than
      previous research on mental disorders either as common causes, markers, or
      mediators.

PMID- 17502803
TI  - Correlates of religious service attendance and contact with religious leaders
      among persons with co-occurring serious mental illness and type 2 diabetes.
AB  - The purpose of this study was to examine the prevalence and correlates of
      religious participation among persons with co-occurring serious mental illness
      and type 2 diabetes. Among 201 outpatients, 53% attended religious services, 36%
      had regular contact with a religious leader, and 15% received assistance from a
      religious leader. Persons with schizophrenia and African Americans were more
      likely to attend services and have contact with religious leaders. Both
      attendance at religious services and regular contact with a religious leader were
      linked to higher quality of life in selected domains, but not associated with
      global health ratings or glycosylated hemoglobin (HbA1c) levels. Results indicate
      that there are important diagnostic and racial differences in religious
      participation, and that religious participation may be a resilience factor that
      supports enhanced quality of life for persons with serious mental illness and
      diabetes.

PMID- 17502804
TI  - Religion and remission of depression in medical inpatients with heart
      failure/pulmonary disease.
AB  - The impact of religious involvement on time to remission of depression was
      examined in older medical inpatients with heart failure and/or chronic pulmonary
      disease (CHF/CPD). Inpatients older than 50 years with CHF/CPD were
      systematically diagnosed with depressive disorder using a structured psychiatric
      interview. Cox proportional hazards regression was used to examine the effects of
      religious involvement on time to remission, controlling for covariates. Of 1000
      depressed patients identified at baseline, follow-up data on depression course
      were obtained on 87%. Patients involved in group-related religious activities
      experienced a shorter time to remission. Although numerous religious measures
      were unrelated by themselves to depression outcome, the combination of frequent
      religious attendance, prayer, Bible study, and high intrinsic religiosity,
      predicted a 53% increase in speed of remission (HR 1.53, 95% CI 1.20-1.94, p =
      0.0005, n = 839) after controls. Patients highly religious by multiple
      indicators, particularly those involved in community religious activities, remit
      faster from depression.

PMID- 17502805
TI  - Gender differences in young adults with first-episode schizophrenia spectrum
      disorders at baseline in the Danish OPUS study.
AB  - Gender differences in age at first onset, duration of untreated psychosis,
      psychopathology, social functioning, and self-esteem were investigated in a group
      of 578 young adults with a first-episode schizophrenia spectrum disorder. The
      mean age at first-onset of symptoms, age at first contact, and duration of
      untreated psychosis were similar for men and women. Men had more severe negative
      symptoms, poorer premorbid functioning, and poorer social networks, whereas women
      had more severe hallucinations. More men than women were substance abusers, were
      unemployed, and lived alone. Women had poorer self-esteem than men, in spite of
      better scores in functioning. Premorbid social adjustment was significantly
      related to the level of negative symptoms and number of friends. Conclusion is
      that men and women with first-episode psychosis showed different
      psychopathological characteristics and different social functioning, which cannot
      be explained by older age of onset for women. Women make more suicide attempts
      and experience lower self-esteem in spite of better social functioning.

PMID- 17502806
TI  - Factors involved in outcome and recovery in schizophrenia patients not on
      antipsychotic medications: a 15-year multifollow-up study.
AB  - This prospective longitudinal 15-year multifollow-up research studied whether
      unmedicated patients with schizophrenia can function as well as schizophrenia
      patients on antipsychotic medications. If so, can differences in premorbid
      characteristics and personality factors account for this? One hundred and forty
      five patients, including 64 with schizophrenia, were evaluated on premorbid
      variables, assessed prospectively at index hospitalization, and then followed up
      5 times over 15 years. At each follow-up, patients were compared on symptoms and
      global outcome. A larger percent of schizophrenia patients not on antipsychotics
      showed periods of recovery and better global functioning (p < .001). The
      longitudinal data identify a subgroup of schizophrenia patients who do not
      immediately relapse while off antipsychotics and experience intervals of
      recovery. Their more favorable outcome is associated with internal
      characteristics of the patients, including better premorbid developmental
      achievements, favorable personality and attitudinal approaches, less
      vulnerability, greater resilience, and favorable prognostic factors. The current
      longitudinal data suggest not all schizophrenia patients need to use
      antipsychotic medications continuously throughout their lives.

PMID- 17502807
TI  - Neurocognitive deterioration in elderly chronic schizophrenia patients with and
      without PTSD.
AB  - Neurocognitive deficits are associated with chronic schizophrenia and aging. We
      investigated whether elderly chronic schizophrenia inpatients who also suffer
      from posttraumatic stress disorder (PTSD) have more severe cognitive impairment
      than elderly schizophrenia inpatients that do not. Fourteen schizophrenia
      inpatients that are Holocaust survivors and suffer from PTSD (survivor group)
      were compared with schizophrenia inpatients not exposed to the holocaust and
      without PTSD (comparison group) using neurocognitive assessments and psychiatric
      evaluation instruments. The survivors performed significantly worse on measures
      of processing speed and visual scanning, recognition memory, and general mental
      status, than the comparison group. Though nonsignificantly, the comparison group
      revealed better performance on tests that measured visuospatial perception,
      visuospatial planning and strategies, organizational and constructional skills.
      The survivor group displayed a greater severity of antipsychotic-induced side
      effects that were not associated with differences in cognitive performance.
      Comorbid PTSD may contribute to the severity of neurocognitive impairment in
      elderly chronic schizophrenia patients.

PMID- 17502808
TI  - Normal personality characteristics in schizophrenia: a review of the literature
      involving the FFM.
AB  - Schizophrenia is generally viewed as a disruption of normal functioning because
      of an underlying core illness. A number of theorists have speculated that this
      core illness may unilaterally disrupt normal personality functioning. However,
      recent data suggests that the relationship may be more complex and reciprocal
      than previously conceptualized. Furthermore, basic personality characteristics
      appear to be associated with numerous clinical phenomena. This article reviews
      the empirical literature pertaining to normal personality characteristics
      [structured around the five-factor model (FFM) of personality] in individuals
      with schizophrenia. Evidence suggests that certain personality characteristics
      may be uniquely related to the etiology of psychosis, as well as symptom
      severity, occupational functioning, cigarette smoking, substance use and violent
      behavior, social isolation, and suicidality in patients with schizophrenia. The
      implications of these findings and suggestions for future research are discussed.

PMID- 17502809
TI  - Subjective evaluations of research participation by persons with mental illness.
AB  - The present study focuses on the subjective experience of psychiatric patients
      who participate in psychobiological research, based on patients' self-reported
      evaluations of the experience. We studied 313 persons with mental illness
      admitted to an inpatient research unit. Each participant was administered the
      Patient Satisfaction Questionnaire, a structured self-report questionnaire
      designed to assess satisfaction with research participation and clinical care.
      Individuals who completed the research protocol were significantly more satisfied
      globally and more likely to express that treatment had been effective. Factors
      contributing to willingness to participate in future research included favorable
      perceptions of: (a) psychoeducation, (b) safety, and (c) comfort level with
      research procedures. Research participants were willing to participate in future
      research regardless of their perception of medication efficacy. This study
      emphasizes the importance of understanding the opinions of persons with mental
      illness who participate in research. Overall, the data suggest that persons with
      mental illness find psychiatric research to be beneficial. Although therapeutic
      misconception cannot be ruled out given the methodology used, at the very least
      the data indicate no sign that subjects found research participation to be
      harmful. Further studies should explore the source of this perception and attempt
      to separate the effect of "therapeutic misconception" from possible real benefit
      of protocol-driven assessment and treatment in a reputable clinical environment.

PMID- 17502810
TI  - Predictors of aggression on the psychiatric inpatient service: self-esteem,
      narcissism, and theory of mind deficits.
AB  - Aggressive behavior committed by inpatients has significant negative effects on
      patients, clinical staff, the therapeutic milieu, and inpatient community as
      whole. Past research examining nonpsychiatric patient groups has suggested that
      elevated self-esteem and narcissism levels as well as self-serving theory of mind
      (ToM) biases may be robust predictors of aggressive behavior. In the present
      study, we examined whether these constructs were useful in predicting aggressive
      acts committed by psychiatric inpatients. Severity of psychiatric symptoms,
      demographic variables and patients' anger, and hostility severity were also
      examined. We found patients who committed acts of aggression were differentiated
      from their nonaggressive counterparts by exhibiting significantly higher levels
      of self-esteem and narcissistic superiority. In addition, aggressors demonstrated
      self-serving ToM biases, attributing more positive attributes to themselves,
      relative to their perceptions of how others viewed them. Aggressors also showed
      increased psychosis, fewer depressive symptoms, and had significantly fewer years
      of formal education than their nonaggressive peers. These results support and
      extend the view that in addition to clinical variables, specific personality
      traits and self-serving attributions are linked to aggressive behavior in acutely
      ill psychiatric patients.

PMID- 17502811
TI  - Are relationship patterns with significant others reenacted with the therapist?:
      a study of early transference reactions.
AB  - This study examines how patients' relationship patterns are reenacted with the
      therapist during the first sessions of psychotherapy. Forty (N = 40) outpatients
      treated with a Brief Psychodynamic Intervention were included in the study. Their
      narratives of relationship episodes with significant others (e.g., mother,
      father, romantic partner, colleagues) were compared with relationship episodes
      with their therapist using the Core Conflictual Relationship Theme method. The
      Core Conflictual Relationship Theme focuses on 3 aspects of patients'
      relationship narratives: what the patient wants from others or from self; how
      others react to his/her wish; and how the patient consequently reacts. Results
      showed that 60% of patients display similar relationship patterns with their
      therapist and with significant others. The patterns that were reenacted with the
      therapist were not the most pervasive ones but were similar to those found in
      relationship episodes involving parents or romantic partners. These findings
      provide some support for the clinical concept of repetition of internalized
      relational patterns with the therapist very early in psychotherapy. Clinical
      implications are discussed.

PMID- 17502812
TI  - Perceived reasons for living at index hospitalization and future suicide attempt.
AB  - It is unclear why certain individuals choose not to engage in suicidal behavior.
      Although important, protective factors against suicidal behavior have seldom been
      studied. The Reasons for Living Inventory is a measure of putative protective
      factors that is inversely related to a history of suicide attempts, but its
      predictive utility remains relatively untested. This study sought to determine
      whether the Reasons for Living Inventory predicts future suicide attempts over a
      2-year period. Depressed inpatients were assessed for reasons for living and were
      followed for 2 years. Follow-up interviews took place at 3 months, 1 year, and 2
      years after discharge from the index hospitalization. Survival analysis indicates
      a high score on the Reasons for Living Inventory predicted fewer future suicide
      attempts within a 2-year period in women but not in men. Perceived reasons for
      living serve as protective factors against suicide attempt in women and not in
      men.

PMID- 17502818
TI  - Predicting visual field loss in ocular hypertensive patients using wavelet
      fourier analysis of GDx scanning laser polarimetry.
AB  - PURPOSE: To predict which ocular hypertensive (OHT) patients later develop a
      visual field loss by applying shape-based analysis (wavelet-Fourier analysis,
      WFA) to retinal nerve fiber layer (RNFL) thickness estimates. METHODS: Visual
      field information and scanning laser polarimetry (SLP) RNFL estimates were
      obtained from both eyes of 122 patients (73 glaucoma and 49 OHT) and 102 healthy
      individuals. WFA was applied to RNFL temporal, superior nasal, inferior, and
      temporal (TSNIT) curves (28 points) of the glaucoma and healthy eyes to obtain a
      classifier. Without modification, the classifier was then applied to the OHT eyes
      (16 OHTconverters and 33 OHTnonconverters). The visual fields of the OHT patients
      (6-month follow-up for a mean period of 4 years) were analyzed using the Advanced
      Glaucoma Intervention Study (AGIS) criteria to identify eyes which developed
      subsequent field loss in this period of time (OHT converters) and those that did
      not (OHT nonconverters). For the OHT converters, the classifier was applied to
      scans from each of three points in time before the initial visual field damage.
      For the OHT nonconverters, the last available scan was used. The accuracy of the
      WFA metric in predicting conversion of OHT eyes was assessed by calculating area
      under the receiver operating characteristic (ROC) curve (area under the ROC
      curve, AUC), sensitivity at 80% specificity, and likelihood ratio. RESULTS: The
      performance (AUC) of WFA in predicting conversion of the OHT eyes from scans
      taken just before visual field loss was 0.83 with a sensitivity (SD)/specificity
      (SD) of 0.76 +/- 0.11/0.80 +/- 0.07 and likelihood ratio (+LR +/- SD) of 3.8 +/-
      1.4. Performance for scans obtained 6 months before the first signs of visual
      field defects was 0.77 (AUC), 0.71 +/- 0.11/0.80 +/- 0.07
      (sensitivity/specificity), and 3.5 +/- 1.4 (+LR +/- SD). Performance was 0.73
      (AUC), 0.59 +/- 0.12/0.8 +/- 0.07 (sensitivity/specificity), and 3.0 +/- 0.12
      (+LR +/- SD) using the earliest available RNFL estimates. CONCLUSION: The WFA
      method of temporal, superior nasal, inferior, and temporal shape analysis offers
      a means of predicting progression in OHT patients before visual field loss.

PMID- 17502820
TI  - Bausch & Lomb products granted new technology intraocular lens designation.

PMID- 17502821
TI  - The precision of wavefront refraction compared to subjective refraction and
      autorefraction.
AB  - PURPOSE: To determine the precision (repeatability) of several methods of
      calculating refraction from higher-order wavefront aberration data and to compare
      these wavefront refractions with lower-order (LO) wavefront refraction,
      subjective refraction, and autorefraction. METHODS: Four clinicians refracted 16
      normal participants aged 23.6 +/- 1.2 years, 69% female with an average spherical
      equivalent refractive error of -3.03 +/- 2.55 D, median sphere -2.50 D (minimum 
      7.50, maximum +4.75), and median cylinder -0.50 D (minimum -3.00, maximum 0).
      Participants were cyclopleged and underwent subjective refraction, autorefraction
      on two machines (Nidek AR-800, Topcon KR-8000), and wavefront sensing using the
      Wavefront Sciences Complete Ophthalmic Analysis System. Wavefront error was used
      to calculate: LO refraction, refractions that incorporated higher-order spherical
      and astigmatism terms from up to the 4th, 6th, and 10th orders (PCM4, PCM6, and
      PCM10), and a method based on optimizing image quality metrics [wavefront
      analysis technology (WAT) refraction]. Within and between examiner agreements for
      total dioptric difference were determined using Bland-Altman limits of agreement
      (LOA). RESULTS: The interexaminer LOA for individual measurements for M, J0, J45
      were: Topcon (+/-0.18, +/-0.10, +/-0.06), Nidek (+/-0.28, +/-0.16, +/-0.09), LO
      (+/-0.17, +/-0.10, +/-0.06), PCM4 (+/-0.26, +/-0.09, +/-0.06), PCM6 (+/-0.37, +/
      0.17, +/-0.34), PCM10 (+/-0.54, +/-0.32, +/-0.40), WAT (+/-0.28, +/-0.20, +/
      0.15), and subjective refraction (+/-0.48, +/-0.20, +/-0.13) and averaging across
      three measures LOA: Topcon (+/-0.15, +/-0.08, +/-0.05), Nidek (+/-0.21, +/-0.13,
      +/-0.07), LO (+/-0.12, +/-0.06, +/-0.04), PCM4 (+/-0.16, +/-0.05, +/-0.04), PCM6
      (+/-0.23, +/-0.09, +/-0.19), PCM10 (+/-0.29, +/-0.19, +/-0.24), and WAT (+/-0.18,
      +/-0.12, +/-0.10). The within-examiner LOA for M, J0, J45 were: Topcon (+/-0.08,
      +/-0.04, +/-0.02), Nidek (+/-0.13, +/-0.07, +/-0.05 D), LO (+/-0.11, +/-0.07, +/
      0.04), PCM4 (+/-0.17, +/-0.07, +/-0.04 D), PCM6 (+/-0.28, +/-0.12, +/-0.24 D),
      PCM10 (+/-0.42, +/-0.24, +/-0.32 D), and WAT (+/-0.19, +/-0.14, +/-0.09 D).
      CONCLUSIONS: All objective refractions except for PCM10 were more repeatable
      across clinicians than subjective refraction. The precision of all refractions
      were improved by an expected amount through averaging over multiple measurements.
      Wavefront refractions were not as precise as standard autorefractions, although
      not clinically significantly worse.

PMID- 17502822
TI  - Relationships between feature search and mobility performance in persons with
      severe visual impairment.
AB  - PURPOSE: Because visual search requires both the ability to discriminate visual
      features and the ability to process information in a large field of view, the
      association between feature search and mobility of visually impaired (VI)
      subjects was studied. METHODS: Forty-four subjects with severe visual impairment
      participated in the study. Feature search performance (2 x 2 deg square target
      amid 1 x 1 deg square distracters) was measured for 8- to 16- and 32-item set
      sizes on 10 x 10, 20 x 20, and 40 x 40 deg fields. Mobility was evaluated on
      indoor high-density obstacle courses under photopic and mesopic illumination.
      RESULTS: In feature search, VI subjects were slower and made more errors than
      normal subjects, but they searched in a parallel fashion. On the mobility task,
      VI subjects walked slower and made more obstacle contacts than age-matched normal
      controls. In VI subjects, performances on feature search and mobility tasks were
      significantly associated, with 37.5% to 66.9 of variations in the mobility
      measurements being accounted for by visual search speed. CONCLUSIONS: Feature
      search reaction time can be a good predictor of VI patients' mobility.

PMID- 17502824
TI  - Refractive error and visual acuity changes in orthokeratology patients.
AB  - PURPOSE: To evaluate the refractive error and visual acuity (VA) at various
      contrast levels in the two eyes of overnight orthokeratology (ortho-k) subjects,
      and to compare their postortho-k VA with the best corrected VA of spectacle
      wearing control subjects matched for age, gender, and initial refractive error.
      METHODS: Distance postortho-k uncorrected and best corrected logMAR VA at four
      different contrast levels of 31 ortho-k (test) subjects (aged 7-35 years old) and
      the best corrected VA of 31 spectacle-wearing (control) subjects were measured
      and compared using the Waterloo Four-Contrast LogMAR VA Chart, which incorporated
      four sets of letters at different contrast levels: 90%, 48%, 21%, and 7%.
      Noncycloplegic manifest refractive error was measured in both eyes. RESULTS: The
      mean +/- SD percentage reductions in spherical equivalent achieved in the current
      study were 92% +/- 11% in the better eye and 84% +/- 14% in the worse eye of the
      test subjects. Postortho-k uncorrected VAs were significantly correlated with the
      residual overall blurring strength (length of the vector representing the
      residual refractive error) in both eyes at all contrast levels. The mean
      postortho-k uncorrected VA in the better eye were 0.00 +/- 0.11, 0.08 +/- 0.11,
      0.21 +/- 0.12, and 0.46 +/- 0.13 with the 90%, 48%, 21%, and 7% contrast charts,
      respectively. These were comparable to the best corrected VA of the better eye of
      the control group with the 90% (-0.03 +/- 0.07) and 48% contrast charts (0.03 +/-
      0.09), but worse than those of the control group with the 21% (0.13 +/- 0.10) and
      7% (0.35 +/- 0.13) contrast charts. Postortho-k VA, with the four different
      contrast charts, improved by 0.07 to 0.12 log units in the better eye and 0.15 to
      0.18 log units in the worse eye after correction of the residual refractive
      error; the improved VA was comparable to the best corrected VA of the control
      group. CONCLUSIONS: Postortho-k visual outcomes were compromised primarily due to
      the presence of residual refractive error. Although the uncorrected postortho-k
      VA was comparable to the best corrected VA of the spectacle wearers at high
      contrast levels, it was worse at low-contrast levels and caused a significant
      between-eye difference at all contrast levels. Therefore, we suggested that
      monocular VA at high- and low-contrast levels should be evaluated for ortho-k
      patients.

PMID- 17502823
TI  - Preoperative assessment of corneal and refractive stability in soft contact lens
      wearing photorefractive candidates.
AB  - PURPOSE: This pilot study compared traditional methodologies; manifest refraction
      and keratometry, with that of newer technologies; corneal topography, and optical
      pachymetry, in assessing corneal and refractive stabilization after soft contact
      lens wear in photorefractive candidates. The timeline differences among these
      various technologies in determining refractive and corneal stability were
      investigated. METHODS: This was a masked prospective observational clinical study
      of full-time soft contact lens subjects on various wear schedules, all eligible
      candidates for photorefractive surgery. Subjects discontinued contact lens wear
      within 30 min of the initial study visit. During each study visit, the same
      sequence of tests were performed (manifest refraction, keratometry, corneal
      topography, and optical pachymetry). The timing of the last visit was determined
      when the four procedures resulted in stable findings when compared with the
      previous visit. RESULTS: Fifteen soft contact lens wearers and five noncontact
      lens wearing controls completed the study. The mean number of days until
      stability of the 15 test subjects were: 10.7 +/- 10.4 days with manifest
      refraction, 16.2 +/- 17.5 days with keratometry, 28.1 +/- 17.7 days with
      topography, and 35.1 +/- 20.8 days with pachymetry. Within the control group,
      intraclass correlation coefficients for all four methods were > or =0.89,
      indicating very little variability. Analysis with the randomized block design
      found statistical differences between traditional and newer technologies in their
      assessment of stability (p < 0.001). One-way Analysis of variance of the various
      soft contact lenses modalities suggested extended hydrogel wearers taking the
      longest time to reach stability after discontinuing full-time contact lens use.
      CONCLUSIONS: Corneal curvature and thickness measurements took the longest to
      achieve consistency. Thus, topography and pachymetry may be better methods to
      determine ocular stability before photorefractive surgery. In light of this
      finding, the current protocol in practice of determining the readiness of contact
      lens candidates for photorefractive surgery may be inadequate.

PMID- 17502825
TI  - Gas permeable (GP) versus non-GP lens wearers: accuracy of orthokeratology in
      myopia reduction.
AB  - PURPOSE: The primary objective of this study is to determine whether there are
      significant differences in visual and refractive outcomes between gas permeable
      (GP) and non-GP wearers following a 1-month period of overnight orthokeratology
      (OK). METHODS: The study included 14 subjects between the ages of 18 and 42
      years. Group 1 consisted of six subjects wearing GP lenses for the correction of
      myopia for, at minimum, 1 year. Group 2 consisted of eight subjects wearing soft
      contact lenses or spectacles for the correction of myopia. All subjects were fit
      into the BE design in Boston XO material and lenses were worn for a period of 1
      month. Unaided visual acuity using high (90%) and low (10%) contrast log MAR
      Bailey-Lovie vision charts, subjective refraction, corneal topography, and slit
      lamp evaluation were performed. Subjects were evaluated at day 1, 7, 14, 21, and
      30. RESULTS: One eye of each subject was considered for analysis; the eye with
      the better response was chosen based on post-OK measures. The mean post-OK
      spherical equivalent was 0.29 +/- 0.55 D in the GP group and 0.37 +/- 0.46 D in
      the non-GP group; the difference was statistically significant (p = 0.03).
      Baseline astigmatism decreased in the non-GP group after OK while there was no
      significant change in the GP group. The mean high contrast acuities were 0.06 +/-
      0.12 in the GP group and 0.17 +/- 0.07 in the non-GP group (p = 0.05), whereas
      the low contrast acuities were 0.18 +/- 0.17 in the GP and 0.02 +/- 0.09 in the
      non-GP group (p = 0.01). CONCLUSIONS: Although the non-GP group has higher post
      OK visual acuity and spherical equivalent statistically, the GP group has
      attained an average unaided acuity of >20/20 and residual myopia <0.5 D.
      Clinically, this shows that OK can be a promising technique in GP wearers.

PMID- 17502826
TI  - Performance standards for toric soft contact lenses.
AB  - PURPOSE: To simplify the clinical assessment of toric soft contact lens (TSCL) on
      eye behavior by establishing a set of standard clinical evaluation techniques.
      The likely performance range expected among the TSCL wearing population was
      determined for a series of lens designs and acceptable performance standards
      indicated for each variable. METHODS: Four prism-ballast, two peri-ballast and
      one dynamic stabilization TSCL designs were each worn by groups of 20 subjects in
      a nondispensing study. After 20 min of lens wear, lenses were assessed, in right
      eyes only, for subjective comfort (100-point scale), lens mislocation (degrees
      deviation from vertical) and rotational recovery after deliberate 30 degrees
      mislocation (degrees/10 blinks). The percentage of lenses orienting within +/-10
      degrees of target orientation (zero rotation) and the variability of orientation
      (standard deviation of mislocation) were also calculated for each lens group.
      RESULTS: Based on partitioning of the data distributions for each variable,
      performance was designated as excellent, acceptable or poor. Corresponding
      performance cut-offs were determined at > or =90, 89 to 80, and <80 for
      subjective comfort, < or =+/-6 degrees , +/-7 degrees to 10 degrees , and >+/-10
      degrees for mislocation, >10 degrees /10 blinks, 10 degrees to 6 degrees /10
      blinks, and <6 degrees /10 blinks for rotational recovery. For groups of wearers
      the appropriate cut-offs were > or =90%, 89 to 70%, and <70% of lenses orienting
      within +/-10 degrees of target orientation and <+/-6 degrees , +/-6 degrees to 10
      degrees , and >+/-10 degrees for variability of orientation. CONCLUSION:
      Techniques suitable for the evaluation of TSCL clinical performance have been
      described and guidelines for the assessment of such lenses established. In the
      process, we have identified potential performance differences that may relate to
      variations in TSCL design.

PMID- 17502827
TI  - The effect of octylglucoside and sodium cholate in Staphylococcus epidermidis and
      Pseudomonas aeruginosa adhesion to soft contact lenses.
AB  - PURPOSE: In this study, the effect of the natural surfactants octylglucoside and
      sodium cholate in inhibiting Staphylococcus epidermidis and Pseudomonas
      aeruginosa adhesion to conventional and silicone-hydrogel contact lenses (CL) was
      assessed. Hydrophobicity was also evaluated to conditioned and nonconditioned CL.
      METHODS: The inhibiting effect of the tested surfactants was determined through
      "in vitro" adhesion studies to conditioned and nonconditioned CL followed by
      image acquisition and cell enumeration. Hydrophobicity was evaluated through
      contact angle measurements using the advancing type technique on air. RESULTS:
      Sodium cholate exhibits a very low capability to inhibit microbial adhesion.
      Conversely, octylglucoside effectively inhibited microbial adhesion in both types
      of lenses. This surfactant exhibited an even greater performance than a
      multipurpose lens care solution used as control. Octylglucoside was the only
      tested surfactant able to lower the hydrophobicity of all CL, which can explain
      its high performance. CONCLUSIONS: The results obtained in this study point out
      the potential of octylglucoside as a conditioning agent to prevent microbial
      colonization.

PMID- 17502828
TI  - The skew ray ambiguity in the analysis of videokeratoscopic data.
AB  - PURPOSE: Skew ray ambiguity is present in most videokeratoscopic measurements
      when azimuthal components of the corneal curvature are not taken into account.
      There have been some reported studies based on theoretical predictions and
      measured test surfaces suggesting that skew ray ambiguity is significant for
      highly deformed corneas or decentered corneal measurements. However, the effect
      of skew ray ambiguity in ray tracing through videokeratoscopic data has not been
      studied in depth. METHODS: We have evaluated the significance of the skew ray
      ambiguity and its effect on the analyzed corneal optics. This has been achieved
      by devising a procedure in which we compared the corneal wavefront aberrations
      estimated from 3D ray tracing with those determined from 2D (meridional based)
      estimates of the refractive power. The latter was possible due to recently
      developed concept of refractive Zernike power polynomials which links the
      refractive power domain with that of the wavefront. Simulated corneal surfaces as
      well as data from a range of corneas (from two different Placido disk-based
      videokeratoscopes) were used to find the limit at which the difference in
      estimated corneal wavefronts (or the corresponding refractive powers) would have
      clinical significance (e.g., equivalent to 0.125 D or more). RESULTS: The
      inclusion/exclusion of the skew ray in the analyses showed some differences in
      the results. However, the proposed procedure showed clinically significant
      differences only for highly deformed corneas and only for large corneal
      diameters. CONCLUSIONS: For the overwhelming majority of surfaces, the skew ray
      ambiguity is not a clinically significant issue in the analysis of the
      videokeratoscopic data indicating that the meridional processing such as that
      encountered in calculation of the refractive power maps is adequate.

PMID- 17502829
TI  - Isomorphism and possible invariance of error cells under spherocylindrical
      transposition.
AB  - PURPOSE: The purpose of this article is to investigate the invariance and
      isomorphism of error cells with cylinder power measured positively and negatively
      in the cylinder-sphere plane. Cells with cylinder power measured positively and
      negatively are mapped to symmetric power space to see whether isomorphism and the
      invariance are conserved under the mapping and spherocylindrical transposition.
      METHOD: Principal powers of refraction are measured and are rounded off to
      multiples of 0.25 D and 1 degrees or 5 degrees , say, for the principal
      meridians. Geometric regions in the cylinder-sphere plane with positive and
      negative cylinder represent uncertainty surrounding the powers and are
      respectively transformed to a plane containing the axis of scalar powers in
      symmetric power space. RESULTS: Cells from principal powers become error cells
      surrounding readings of cylinder and sphere as well as error regions about
      astigmatic powers. These are presented in the plane for scalar powers and
      semipowers of positive and negative cylinders. In symmetric power space, planes
      containing the axis of scalar powers are distinguished from one another by the
      cylinder axis of the lens power. CONCLUSION: Although error cells in clinical
      measure are not invariant under spherocylindrical transposition, cells
      represented in positive cylinder form have the same shape as cells for which the
      power is expressed in negative cylinder form. Error cells in symmetric power
      space about powers in negative cylinders can be rotated about the axis of scalar
      powers to coincide perfectly with cells about powers in positive cylinder form
      for near spherical and astigmatic powers. The error regions in symmetric power
      space do not depend on the spherocylindrical form in which the original
      measurements are made and their isomorphism is conserved in the mapping.

PMID- 17502830
TI  - Validation of the associations between single nucleotide polymorphisms or
      haplotypes and responses to disease-modifying antirheumatic drugs in patients
      with rheumatoid arthritis: a proposal for prospective pharmacogenomic study in
      clinical practice.
AB  - BACKGROUND: For prevention of joint destruction in rheumatoid arthritis, optimal
      management of therapy with disease-modifying antirheumatic drugs is essential.
      Pharmacogenomic evidence, if reliable, may be incorporated in the treatment of
      rheumatoid arthritis to achieve a more efficient activity control with minimized
      adverse events. METHODS: We conducted retrospective studies to validate our
      previous three different results about the association between adverse events or
      efficacy of two different disease-modifying antirheumatic drugs and genomic
      variations. Association between single nucleotide polymorphisms in N
      acetyltransferase 2 gene (NAT2) and adverse events by sulfasalazine and
      association between C677T or A1298C in 5,10-methylenetetrahydrofolate reductase
      gene (MTHFR) and responses to methotrexate were examined. RESULTS: Patients
      without the wild-type haplotype at NAT2 were more likely to suffer from overall
      adverse events [n=186, P=0.001, relative risk (RR) 3.31, 95% confidence interval
      (CI) 1.76-6.22] and severe adverse events (P=0.015, RR 24.6, 95% CI 2.37-254.53)
      by sulfasalazine. Patients with the T allele at C677T in MTHFR were more
      susceptible to overall adverse events (n=156, P=0.003; RR 2.4, 95% CI 1.29-4.55)
      while patients with the C allele at A1298C were less likely to be treated with a
      higher dose (>6 mg/week) of methotrexate in one year of treatment (n=159,
      P=0.008, RR 1.84, 95% CI 1.12-3.01). In all three association studies, the
      results were essentially the same as previously reported. CONCLUSION: As three
      studies on the associations between genomic variations and adverse events or
      efficacy of two different disease-modifying antirheumatic drugs were replicated,
      the usefulness of the tests is worth being tested in clinical practice.

PMID- 17502831
TI  - Androgen receptor gene CAG repeat length as a modifier of the association between
      persistent organohalogen pollutant exposure markers and semen characteristics.
AB  - OBJECTIVES: Exposure to persistent organohalogen pollutants was suggested to
      impair male reproductive function. A gene-environment interaction has been
      proposed. No genes modifying the effect of persistent organohalogen pollutants on
      reproductive organs have yet been identified. We aimed to investigate whether the
      CAG and GGN polymorphisms in the androgen receptor gene modify the effect of
      persistent organohalogen pollutant exposure on human sperm characteristics.
      METHODS: Semen and blood from 680 men [mean (SD) age 34 (10) years] from
      Greenland, Sweden, Warsaw (Poland) and Kharkiv (Ukraine) were collected.
      Persistent organohalogen pollutant exposure was assessed by measuring serum
      levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl
      dichloroethene (p,p'-DDE). Semen characteristics (volume, sperm concentration,
      total count, proportion of progressively motile and morphology) and DNA
      fragmentation index (DFI) were determined. CAG and GGN repeat lengths were
      determined by direct sequencing of leukocyte DNA. RESULTS: A statistically
      significant interaction was found between the CB-153 group and CAG repeat
      category in relation to sperm concentration and total sperm count (P=0.03 and
      0.01, respectively). For p,p'-DDE, in the European cohorts a significant
      interaction was found in relation to DFI (P=0.01). For CAG<20, sperm
      concentration and total sperm count were 35 and 42% lower, respectively, when the
      group with CB-153 exposure above median was compared with that below the median.
      DFI was 40% higher in the high p,p'-DDE exposure group for CAG<or=21.
      CONCLUSIONS: This study indicated that the androgen receptor CAG repeat length
      might modify the susceptibility of an individual to the adverse effects of
      persistent organohalogen pollutant exposure on semen quality. Other studies
      regarding this matter are warranted.

PMID- 17502832
TI  - MRP2 haplotypes confer differential susceptibility to toxic liver injury.
AB  - OBJECTIVES: Multidrug resistance protein 2 (MRP2, ABCC2) plays an important role
      in the biliary clearance of a wide variety of endogenous and exogenous toxic
      compounds. Therefore, polymorphisms and mutations in the MRP2 gene may affect
      individual susceptibility to hepatotoxic reactions. METHODS: Associations between
      genetic variations of MRP2 and toxic hepatitis were investigated using integrated
      population genetic analysis and functional molecular studies. RESULTS: Using a
      gene scanning method, 12 polymorphisms and mutations were found in the MRP2 gene
      in a Korean population. Individual variation at these sites was analyzed by
      conventional DNA screening in 110 control subjects and 94 patients with toxic
      hepatitis induced mostly by herbal remedies. When haplotypes were identified,
      over 85% of haploid genes belonged to the five most common haplotypes. Among
      these, a haplotype containing the g.-1774delG polymorphism showed a strong
      association with cholestatic or mixed-type hepatitis, and a haplotype containing
      the g.-1549G>A, g.-24C>T, c.334-49C>T, and c.3972C>T variations was associated
      with hepatocellular-type hepatitis. A comprehensive functional study of these
      sites revealed that genetic variations in the promoter of this gene are primarily
      responsible for the susceptibility to toxic liver injuries. The g.-1774delG
      variation and the combined variation of g.-1549G>A and g.-24C>T decreased MRP2
      promoter activity by 36 and 39%, respectively. In addition, the promoter carrying
      the g.-1774delG allele showed a defect in the bile acid-induced induction of
      promoter activity. CONCLUSIONS: These results suggest that genetic variations of
      MRP2 are an important predisposing factor for herbal-induced or drug-induced
      toxic liver injuries.

PMID- 17502833
TI  - Tagging single nucleotide polymorphisms in excision repair cross-complementing
      group 1 (ERCC1) and risk of primary lung cancer in a Chinese population.
AB  - BACKGROUND AND OBJECTIVE: Low nucleotide excision repair (NER) capacity has been
      associated with increased risk of lung cancer. Excision repair cross
      complementing group 1 (ERCC1) is one of the NER core enzymes, and polymorphisms
      in ERCC1 may lead to altered repair function of the enzyme and therefore confer
      predisposition to cancer. The goal of this study was to test the hypothesis that
      common variants in ERCC1 were associated with lung cancer risk. METHODS: The
      genotyping analyses for 7 selected single nucleotide polymorphisms in ERCC1 using
      the TaqMan assay was conducted in a case-control study of 1010 patients with
      incident lung cancer and 1011 cancer-free controls in a Chinese population.
      RESULTS: We found that the variant genotypes of the rs3212948 C allele were
      associated with significantly decreased risk of lung cancer [adjusted odds ratio
      (OR)=0.73 (95% CI=0.60-0.88) for CG; 0.96 (95% CI=0.65-1.41) for CC and 0.76 (95%
      CI=0.63-0.91) for CG/CC, compared with the GG genotype]. Similarly, a significant
      protective effect was also evident for the variant genotypes of rs1007616 C/T
      [adjusted OR=0.72 (95% CI=0.59-0.89) for CT; 0.90 (95% CI=0.61-1.35) for TT and
      0.75 (95% CI=0.62-0.91) for CT/TT, compared with the CC genotype]. Stratified
      analysis revealed that the protective effects of these 2 single nucleotide
      polymorphisms were both more evident among young patients and patients without
      family history of cancer. Consistently, when assessing each unique haplotype
      compared with the most common haplotype 'TAGCACG', lung cancer risk was
      significantly decreased among patients who carried the haplotype 'TCCCATT' with
      the variant rs3212948C and rs1007616T alleles (P value=0.0340, P-sim=0.0325,
      adjusted OR=0.78; 95% CI=0.63-0.97). CONCLUSION: These findings indicate that
      ERCC1 polymorphisms may contribute to the etiology of lung cancer. Further
      functional studies were warranted to elucidate the mechanism of the associations.

PMID- 17502834
TI  - Beta-2-adrenergic receptor polymorphisms in cystic fibrosis.
AB  - OBJECTIVES: Cystic fibrosis (CF), an autosomal recessive disease affecting the
      lung, pancreas, gut, liver, and reproductive tract, is caused by mutations in the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a
      cyclic adenosine 3', 5' monophosphate-regulated chloride channel. The variability
      of disease progression among patients with CF suggests effects of genetic
      modifiers of disease. Beta-2 adrenergic receptors (beta2AR), which are abundant
      in airway epithelial cells, accelerate the formation of cyclic adenosine 3', 5'
      monophosphate, which can modulate CFTR activity and affect smooth muscle
      contractility. We tested the hypothesis that genetic variants of the beta2AR
      gene, which have been shown to influence receptor desensitization, are more
      frequent in patients than in controls. METHODS: We genotyped 130 adult CF
      patients and 1 : 1 age-matched, sex-matched, and ethnicity-matched normal
      volunteers for GlyArg and GlnGlu beta2AR. RESULTS: We found that CF patients were
      more likely than controls to be Gly homozygotes (48 and 32%, respectively)
      (P<0.01) and Glu homozygotes (29 and 10%, respectively) (P<0.01). CONCLUSIONS:
      Our results, showing a higher frequency of Gly and Glu beta2AR alleles in adult
      CF patients than in the control population, contrast with data from children with
      CF, who are reported to have lower frequency of Gly and similar frequency of G1u,
      and with data from young adults with CF, who showed no differences in frequencies
      of beta2AR variants. The GlyGlu variant of beta2AR may have properties that lead
      to enhanced beta2AR function, resulting in the upregulation of CFTR activity and
      the improvement of CF disease.

PMID- 17502835
TI  - Genetic polymorphisms of CYP2B6 affect the pharmacokinetics/pharmacodynamics of
      cyclophosphamide in Japanese cancer patients.
AB  - OBJECTIVE: To evaluate the effects of genetic polymorphisms of drug metabolizing
      enzymes on the pharmacokinetics of cyclophosphamide and its active metabolite, 4
      hydroxycyclophosphamide, and on the pharmacodynamics. EXPERIMENTAL DESIGN: One
      hundred and three Japanese patients with malignant lymphoma or breast cancer
      treated with cyclophosphamide (500-750 mg/m) participated in this study. The
      plasma concentrations of cyclophosphamide and 4-hydroxycyclophosphamide were
      determined by high-performance liquid chromatography, and pharmacokinetic
      parameters were calculated. The genotypes of CYP2B6, CYP2C19, CYP3A4, CYP3A5,
      ALDH1A1, GST genes were determined by allele-specific polymerase chain reaction
      or polymerase chain reaction-restriction-fragment length polymorphism. RESULTS: A
      large interindividual difference (54-fold) was observed in the area under the
      curve ratio of 4-hydroxycyclophosphamide/cyclophosphamide calculated as the
      metabolic index. We first proved that leukocytopenia and neutropenia were
      significantly (P<0.01) related to the area under the curve of 4
      hydroxycyclophosphamide. We found that the homozygotes of CYP2B6*6 (Q172H and
      K262R) showed significantly (P<0.05) higher clearance and shorter half-life of
      cyclophosphamide than heterozygotes and homozygotes of CYP2B6*1. The small sample
      size, however, limited the impact. On the other hand, it was clearly demonstrated
      that the patients possessing the single nucleotide polymorphisms of the CYP2B6
      gene, g.-2320T>C, g.-750T>C (5'-flanking region), g.15582C>T (intron 3), or
      g.18492T>C (intron 5), had significantly lower area under the curve ratios of 4
      hydroxycyclophosphamide/cyclophosphamide, indicating a decreased cyclophosphamide
      4-hydroxylation. Of particular importance was the finding that leukocytopenia was
      significantly related to the single nucleotide polymorphisms g.-2320T>C, g.
      750T>C, and g.18492T>C in CYP2B6 gene, which are highly linked. No relationship
      was observed between the pharmacokinetics of cyclophosphamide or 4
      hydroxycyclophosphamide and genetic polymorphisms of the other enzymes.
      CONCLUSIONS: We clarified that the single nucleotide polymorphisms in the
      promoter region or introns in the CYP2B6 affect the potency of cyclophosphamide
      activation to 4-hydroxycyclophosphamide. This information would be valuable for
      predicting adverse reactions and the clinical efficacy of cyclophosphamide.

PMID- 17502836
TI  - Gender-specific differences in expression in human lymphoblastoid cell lines.
AB  - Women and men have different risks for certain diseases and they often respond
      differently to treatment. These differences could be due to the sex-specific
      differences in the expression of genes related to primary disease susceptibility
      or pharmacodynamic targets. To evaluate the sex-specific pattern of gene
      expression, we compared gene expression levels using a publicly available
      microarray dataset of 233 (115 women and 118 men) lymphoblastoid cell lines. From
      the 4799 probes meeting a specified minimal level of expression, 10 genes
      (P<0.005, permutation adjusted false discovery rate less than 50%) located on
      autosomal chromosomes were identified using a permutation-based approach. These
      genes were found to be over-represented in certain gene ontology terms of
      biological process (cell adhesion, apoptosis, transcription and signal
      transduction), and molecular function (structural molecule activity, zinc ion
      binding, transcription factor activity and protein binding). A Kyoto Encyclopedia
      of Genes and Genomes pathway analysis indicated that two known pathways are over
      represented: adherens junction and cytokine-cytokine receptor interaction.

PMID- 17502837
TI  - Pharmacogenetic interaction between paraoxonase-1 gene promoter polymorphism C
      107T and statin.
AB  - OBJECTIVE: The aims of this study were to compare the impact of transcription
      factors, together with statin, on the paraoxonase promoter alleles defined by the
      C(-107T) polymorphism and to more clearly define regions of the paraoxonase
      promoter implicated in the actions of transcription factors. METHODS: Expression
      studies of promoter alleles were performed with reporter gene cassettes
      transfected into HepG2 cells, complemented by nuclease protection assays,
      electrophoretic mobility shift assays and statin therapy in patients. RESULTS:
      One region only of the minimal promoter fragment that up-regulates activity was
      protected by transcription factors and nuclear extracts. It spanned nucleotides 
      119 to -100, encompassing the C(-107)T polymorphism. Sp1 was effective alone in
      protecting this region, with its effect greatly enhanced by SREBP-2. The
      protective effect was much stronger for the C vs. T promoter allele. Expression
      studies confirmed the stimulatory influence of SREBP-2 was significantly stronger
      for the C promoter. Simvastatin up-regulated promoter activity of the C allele,
      but had a minor effect on the T allele. Hypercholesterolemic patients homozygous
      for the C allele showed a significant increase in serum paraoxonase-1 activity
      and mass during treatment with simvastatin, whereas patients homozygous for the T
      allele showed no increase. CONCLUSIONS: The study has delimited the region
      responsive to transcription factors to a sequence surrounding the C(-107)T
      polymorphism of the paraoxonase-1 gene, and demonstrated an interaction at this
      sequence between Sp1 and SREBP-2. SREBP-2 and statin strongly up-regulated the C,
      but not the T allele. The results suggest a pharmacogenetic interaction between
      the promoter and simvastatin, which can influence serum paraoxonase in patients.

PMID- 17502838
TI  - Proceedings of the State of the Science Conference, October 2006, Washington, DC,
      USA.

PMID- 17502839
TI  - Inhalation injury: research progress and needs.

PMID- 17502841
TI  - [Taxonomy and phylogenetic analysis of infectious Nocardia strains isolated from
      clinical samples].
AB  - Following recent advances in medical technology, the increased number of
      immunocompromised patients such as those with organ transplants has led to an
      increase in opportunistic infections due to Nocardia. Although nocardiosis has
      been considered to be rare, recent reports indicate that the incidence of the
      infection is increasing. The Nocardia asteroides group is the principal source of
      infectious species, but the definition of species in Nocardia is problematic
      because species identification of N. asteroides has been based on mainly
      morphological and biochemical properties. Additionally, it was assumed that a
      clinical strain with properties that did not fully coincide with existing species
      was N. asteroides sensu lato. This caused problems in both clinical and
      taxonomical fields, and reclassification of N. asteroides sensu lato was
      necessary. Therefore, determination of the appropriate taxonomic position of N.
      asteroides sensu lato that is now classified as N. asteroides sensu stricto was
      conducted using a molecular phylogenetic method. From 1965 to 2001, twenty-two
      strains of N. asteroides sensu lato were isolated from clinical samples. The
      phylogenetic tree using 16S rDNA sequences and detailed biochemical characters on
      the 22 isolates was determined. Results revealed that nine strains should be
      reclassified into species other than N. asteroides sensu stricto, and we proposed
      nine new species of the genus Nocardia. In addition, we proposed eight other new
      species of the genus Nocardia from other samples; hence seventeen new species
      were proposed in total. We also reported the first infectious cases due to
      Nocardia beijingensis, Nocardia transvalensis and Nocardia pseudobrasiliensis in
      Japan.

PMID- 17502840
TI  - Hormone therapy and coronary heart disease in young women.
AB  - OBJECTIVE: Because the Women's Health Initiative randomized controlled trial (WHI
      RCT) primarily studied older women, it is unresolved whether hormone therapy
      might prevent coronary heart disease in younger women. Given the similarity
      between our UK General Practice Research Database (GPRD) study of older women and
      the WHI RCT, the GPRD methodology was used to study a cohort of younger women.
      DESIGN: Women ages 50 to 55 years were investigated using data from the GPRD to
      simulate the WHI RCT in a manner similar to our initial study of older women.
      This study compared 30,102 unexposed and 20,654 exposed women treated with
      conjugated estrogens and norgestrel. RESULTS: Myocardial infarction was not
      altered significantly by hormone therapy (adjusted hazard ratio 0.91; 95% CI,
      0.69-1.20). Stroke, venous thromboembolic events, breast cancer, and hip fracture
      were similar to both the GPRD study of older women and the WHI RCT. Although
      death was decreased in the total cohort, similar to older women, it was not
      altered significantly in a subset without missing covariate data. CONCLUSION: The
      similar results of the GPRD studies in younger and older women and between the
      GPRD and the WHI RCT suggest that hormone therapy does not prevent coronary heart
      disease in younger postmenopausal women. This study also demonstrates that
      investigation using a primary care electronic medical record database can expand
      the generalizability of findings from an RCT.

PMID- 17502842
TI  - [Clinical study of 57 cases of infection with Trichophyton tonsurans examined at
      a dermatology clinic in Saga Prefecture, Japan].
AB  - This paper is a clinical study of 57 cases of infection with Trichophyton
      tonsurans (T. tonsurans) examined in our clinic between January 2004 and July
      2006. The patients were 31 high school students, 19 junior high school students,
      2 primary school students, 1 kindergartener, and 4 sports instructors. The
      male:female ratio was 51:6. Most patients were male Judo practitioners. Patients
      were clinically categorized as follows: 13 cases of tinea capitis {10 containing
      black dot ringworms (BDR), 2 scaled, and 1 with inflammation}, 41 cases of tinea
      corporis, 1 case of tinea manum, and 7 carriers. Five patients displayed both
      tinea capitis and tinea corporis. Among tinea corporis patients, 21 displayed
      annular erythemas, whereas 19 displayed small circular eythemas characterized by
      a lightly inflamed non-typical rush. In 3 tinea corporis cases, we sampled T.
      tonsurans from hair grown inside the skin rash. Eleven of the tinea corporis
      patients displayed multiple lesions. Compared to patients with singular lesions,
      these 11 cases had a larger degree of comorbidity with BDR or HB positivity. A 6
      8 week treatment with griseofulvin was efficient in 90% of the tinea capitis
      cases. Tinea corporis patients were healed following a 4-9 week treatment with
      topical antifungals and griseofulvin. When examining T. tonsurans infections,
      patients with BDR or lightly inflamed tinea corporis as well as asymptomatic
      carriers can be easily overlooked or misdiagnosed. Therefore, we suggest that
      mycological examination, including careful observation of the rash and KOH mount,
      is essential in these cases.

PMID- 17502843
TI  - [A case of chromomycosis caused by Fonsecaea pedrosoi presenting as a small
      plaque on the left upper arm: a review of reported cases of dematiaceous fungal
      infection in Japan].
AB  - We report a case of a 67-year-old woman with chromomycosis on the left upper arm.
      The plaque was a very small, erythematous and scaly lesion with a diameter of 1.5
      cm. Fonsecaea pedrosoi was isolated as the causal fungus, and a number of
      Phialophora type conidia, the formation of which is considered rare, were
      observed. Treatment involved surgical excision of the lesion with a 5 mm margin.
      Follow up three years later revealed no recurrence. In Japan, 536 patients with
      chromomycosis were reported from 1955 to 2004. This consisted of 296 cases from
      1955 to 1981 as reported by Fukushiro, and 240 cases from 1982 to 2004 as
      reviewed by us. Our examination of data showed that the most common causal fungi
      was F. pedrosoi with 137 cases (57.15%), followed by Exophiala jeanselmei with a
      total of 41 cases (17.15%), other fungal species comprised of 16 cases (6.7%),
      Phialophora verrucosa in 9 cases ( 3.8%) and E. dermatitidis in 4 cases (1.7%).
      Compared to the previous report by Fukushiro, the incidence of infection with E.
      jeanselmei had increased. Of the 235 cases we reported, the site of infection
      involved: upper extremities in 91 (38.7%), face and neck in 42 (17.9%), buttocks
      in 41 (17.4%), lower extremities in 33 (14%) and body in 23 (9.8%). Compared to
      Fukushiro's report, cases affecting the lower extremities had decreased, whilst
      cases involving the buttocks had increased. Overall, the treatment for
      chromomycosis was either oral administration of antifungal agents, excision,
      thermotherapy, or a combination of these methods.

PMID- 17502844
TI  - [A case of black dot ringworm on the right forearm caused by Trichophyton
      tonsurans].
AB  - We report a case of black dot ringworm on the right forearm caused by
      Trichophyton (T.) tonsurans. A 16-year-old male high school Judo-wrestler visited
      our clinic on September 30, 2005, complaining of a round erythematosquamous
      eruption with a distinct margin on the right forearm. Black dots were observed in
      the lesion. KOH-Parker ink prepared direct microscopy revealed abundant large
      endotrix arthroconidia in the hair shaft. Culture yielded yellowish-brown
      colonies. The isolate produced numerous round, short club-shaped microconidia
      along the hyphae unstained with lactophenol cotton blue (resembling matchsticks)
      and chlamydospores. PCR-RFLP analysis of internal transcribed spacer regions of
      ribosomal DNA revealed a banding pattern compatible with T. tonsurans. The lesion
      was cured by daily administration of 125 mg of terbinafine for 13 weeks.

PMID- 17502845
TI  - [Antifungal activity of the novel adduct, GX-95, of silver with nanometer-scale
      particles to peptidic hydrolysates from collagen].
AB  - Silver has long been known to have an antimicrobial activity against bacteria and
      other microorganisms, and has been used as eating utensils, as dental fillings
      and so on. We developed a novel adduct, GX-95, of silver with nanometer-scale
      particles to peptidic hydrolysates from collagen. Antifungal activity of the
      adduct against pathogenic yeasts and filamentous fungi was examined in terms of
      minimal inhibitory concentrations (MICs). GX-95 was found to possess strong and
      broad antifungal activities against all fungi examined in the following MICs:
      0.25 to 0.31 microg/ml for Candida albicans including resistant strains to
      fluconazole, itraconazole and flucytosine, 0.05 to 0.2 microg/ml for Cryptococcus
      neoformans strains, 0.025 to 0.4 microg/ml for Aspergillus fumigatus strains, 0.4
      microg/ml for Trichophyton rubrum, and 0.05 microg/ml for Cladophialophora
      carrionii.

PMID- 17502846
TI  - Two new non-competitive mGlu1 receptor antagonists are potent tools to unravel
      functions of this mGlu receptor subtype.
AB  - The validation of the selective, potent and systemically active non-competitive
      mGlu1 antagonists YM-298198 and JNJ16259685 in a physiological functional assay
      will facilitate elucidation of this receptor's role in brain function and as a
      potential drug target.

PMID- 17502847
TI  - Potent and specific action of the mGlu1 antagonists YM-298198 and JNJ16259685 on
      synaptic transmission in rat cerebellar slices.
AB  - BACKGROUND AND PURPOSE: Specific and selective inhibitors for mGlu1 receptors are
      presently inadequate. A new generation of non-competitive mGlu1 antagonists with
      low nanomolar potencies is emerging. We evaluated two new compounds, YM-298198
      and JNJ16259685, for effectiveness, potency and specificity for the first time in
      a brain slice preparation. EXPERIMENTAL APPROACH: Patch-clamp recording of
      Purkinje neurones in cerebellar slices were obtained. The slow mGlu1-mediated
      EPSP was used to establish a concentration-response curve. Fast excitatory
      synaptic inputs were tested for non-specific effects. KEY RESULTS: YM-298198 and
      JNJ16259685 inhibited the synaptic activation of mGlu1 in a concentration
      dependent manner (IC(50) values of 24 nM and 19 nM, respectively). The
      antagonists were slow to inhibit and to reverse on washout, probably due to their
      lipophilic nature. There were no non-specific effects on fast AMPA receptor
      mediated synaptic transmission in the cerebellum. CONCLUSIONS AND IMPLICATIONS:
      These compounds are more than a thousand-fold more potent than previously
      available compounds. Their selectivity and specificity will be very useful for
      studying the role of mGlu1 receptors both in vitro and in vivo.

PMID- 17502848
TI  - Augmentation of spinal morphine analgesia and inhibition of tolerance by low
      doses of mu- and delta-opioid receptor antagonists.
AB  - BACKGROUND AND PURPOSE: Ultralow doses of naltrexone, a non-selective opioid
      antagonist, have previously been found to augment acute morphine analgesia and
      block the development of tolerance to this effect. Since morphine tolerance is
      dependent on the activity of micro and delta receptors, the present study
      investigated the effects of ultralow doses of antagonists selective for these
      receptor types on morphine analgesia and tolerance in tests of thermal and
      mechanical nociception. EXPERIMENTAL APPROACH: Effects of intrathecal
      administration of mu-receptor antagonists, CTOP (0.01 ng) or CTAP (0.001 ng), or
      a delta-receptor antagonist, naltrindole (0.01 ng), on spinal morphine analgesia
      and tolerance were evaluated using the tail-flick and paw-pressure tests in rats.
      KEY RESULTS: Both micro and delta antagonists augmented analgesia produced by a
      sub-maximal (5 microg) or maximal (15 microg) dose of morphine. Administration of
      the antagonists with morphine (15 microg) for 5 days inhibited the progressive
      decline of analgesia and prevented the loss of morphine potency. In animals
      exhibiting tolerance to morphine, administration of the antagonists with morphine
      produced a recovery of the analgesic response and restored morphine potency.
      CONCLUSIONS AND IMPLICATIONS: Combining ultralow doses of micro- or delta
      receptor antagonists with spinal morphine augmented the acute analgesic effects,
      inhibited the induction of chronic tolerance and reversed established tolerance.
      The remarkably similar effects of micro- and delta-opioid receptor antagonists on
      morphine analgesia and tolerance are interpreted in terms of blockade of the
      latent excitatory effects of the agonist that limit expression of its full
      activity.

PMID- 17502849
TI  - The synthetic cannabinoid HU210 induces spatial memory deficits and suppresses
      hippocampal firing rate in rats.
AB  - BACKGROUND AND PURPOSE: Previous work implied that the hippocampal cannabinoid
      system was particularly important in some forms of learning, but direct evidence
      for this hypothesis is scarce. We therefore assessed the effects of the synthetic
      cannabinoid HU210 on memory and hippocampal activity. EXPERIMENTAL APPROACH:
      HU210 (100 microg kg(-1)) was administered intraperitoneally to rats under three
      experimental conditions. One group of animals were pre-trained in spatial working
      memory using a delayed-matching-to-position task and effects of HU210 were
      assessed in a within-subject design. In another, rats were injected before
      acquisition learning of a spatial reference memory task with constant platform
      location. Finally, a separate group of animals was implanted with electrode
      bundles in CA1 and CA3 and single unit responses were isolated, before and after
      HU210 treatment. KEY RESULTS: HU210 treatment had no effect on working or short
      term memory. Relative to its control Tween 80, deficits in acquisition of a
      reference memory version of the water maze were obtained, along with drug-related
      effects on anxiety, motor activity and spatial learning. Deficits were not
      reversed by the CB(1) receptor antagonists SR141716A (3 mg kg(-1)) or AM281 (1.5
      mg kg(-1)). Single unit recordings from principal neurons in hippocampal CA3 and
      CA1 confirmed HU210-induced attenuation of the overall firing activity lowering
      both the number of complex spikes fired and the occurrence of bursts. CONCLUSIONS
      AND IMPLICATIONS: These data provide the first direct evidence that the
      underlying mechanism for the spatial memory deficits induced by HU210 in rats is
      the accompanying abnormality in hippocampal cell firing.

PMID- 17502856
TI  - Filaggrin's fuller figure: a glimpse into the genetic architecture of atopic
      dermatitis.
AB  - Prevalent mutations in the FLG gene underlie the common skin disorder ichthyosis
      vulgaris and are significant risk factors for atopic dermatitis (eczema). The
      recent publication of a strategy to sequence this difficult gene identifies a
      spectrum of both prevalent and rare mutations that collectively have a
      significant impact on susceptibility to atopic disease.

PMID- 17502851
TI  - The antimalarial drugs quinine, chloroquine and mefloquine are antagonists at 5
      HT3 receptors.
AB  - BACKGROUND AND PURPOSE: The antimalarial compounds quinine, chloroquine and
      mefloquine affect the electrophysiological properties of Cys-loop receptors and
      have structural similarities to 5-HT(3) receptor antagonists. They may therefore
      act at 5-HT(3) receptors. EXPERIMENTAL APPROACH: The effects of quinine,
      chloroquine and mefloquine on electrophysiological and ligand binding properties
      of 5-HT(3A) receptors expressed in HEK 293 cells and Xenopus oocytes were
      examined. The compounds were also docked into models of the binding site. KEY
      RESULTS: 5-HT(3) responses were blocked with IC (50) values of 13.4 microM, 11.8
      microM and 9.36 microM for quinine, chloroquine and mefloquine. Schild plots
      indicated quinine and chloroquine behaved competitively with pA (2) values of
      4.92 (K (B)=12.0 microM) and 4.97 (K (B)=16.4 microM). Mefloquine displayed
      weakly voltage-dependent, non-competitive inhibition consistent with channel
      block. On and off rates for quinine and chloroquine indicated a simple
      bimolecular reaction scheme. Quinine, chloroquine and mefloquine displaced
      [(3)H]granisetron with K (i) values of 15.0, 24.2 and 35.7 microM. Docking of
      quinine into a homology model of the 5-HT(3) receptor binding site located the
      tertiary ammonium between W183 and Y234, and the quinoline ring towards the
      membrane, stabilised by a hydrogen bond with E129. For chloroquine, the quinoline
      ring was positioned between W183 and Y234 and the tertiary ammonium stabilised by
      interactions with F226. CONCLUSIONS AND IMPLICATIONS: This study shows that
      quinine and chloroquine competitively inhibit 5-HT(3) receptors, while mefloquine
      inhibits predominantly non-competitively. Both quinine and chloroquine can be
      docked into a receptor binding site model, consistent with their structural
      homology to 5-HT(3) receptor antagonists.

PMID- 17502850
TI  - The alpha7 nicotinic acetylcholine receptor as a pharmacological target for
      inflammation.
AB  - The physiological regulation of the immune system encompasses comprehensive anti
      inflammatory mechanisms that can be harnessed for the treatment of infectious and
      inflammatory disorders. Recent studies indicate that the vagal nerve, involved in
      control of heart rate, hormone secretion and gastrointestinal motility, is also
      an immunomodulator. In experimental models of inflammatory diseases, vagal nerve
      stimulation attenuates the production of proinflammatory cytokines and inhibits
      the inflammatory process. Acetylcholine, the principal neurotransmitter of the
      vagal nerve, controls immune cell functions via the alpha7 nicotinic
      acetylcholine receptor (alpha7nAChR). From a pharmacological perspective,
      nicotinic agonists are more efficient than acetylcholine at inhibiting the
      inflammatory signaling and the production of proinflammatory cytokines. This
      'nicotinic anti-inflammatory pathway' may have clinical implications as treatment
      with nicotinic agonists can modulate the production of proinflammatory cytokines
      from immune cells. Nicotine has been tested in clinical trials as a treatment for
      inflammatory diseases such as ulcerative colitis, but the therapeutic potential
      of this mechanism is limited by the collateral toxicity of nicotine. Here, we
      review the recent advances that support the design of more specific receptor
      selective nicotinic agonists that have anti-inflammatory effects while eluding
      its collateral toxicity.

PMID- 17502857
TI  - Common ground?: Tetracyclines, matrix metalloproteinases, pustular dermatoses,
      and loxoscelism.
AB  - The fear of spiders is ancient and common throughout much of the world. Skin
      ulceration and necrosis due to Loxosceles spider envenomation ("bites") is among
      the best known sequelae of a usually accidental encounter. Therapies for
      Loxosceles envenomations either are not well documented or have adverse side
      effects that limit their use by generalists. Based on in vitro and in vivo
      studies in rabbits injected with purified or recombinant sphingomyelinase D2,
      Paixao-Cavalcante et al. (2007) propose in this issue that topical tetracyclines
      could become safe, efficacious therapy for cutaneous loxoscelism.

PMID- 17502858
TI  - Cross-linking of elafin/SKALP to elastic fibers in photodamaged skin: too much of
      a good thing?
AB  - Muto et al. report that UVA light induces the expression of elafin, a potent
      elastase inhibitor, in skin fibroblasts. Elafin binds to elastic fibers by
      transglutaminase-mediated cross-linking and protects against proteolytic
      breakdown. Decreased degradation could contribute to accumulation of elastotic
      material in photodamaged skin. Elastase and its locally produced inhibitors play
      a role in actinic elastosis.

PMID- 17502859
TI  - Opioids and the skin: "itchy" perspectives beyond analgesia and abuse.
AB  - Opioids are intimately linked to central pain inhibition and their abuse
      potential. Thus, peripheral opioid receptors in the skin have been studied
      initially with a focus on their peripheral analgesic properties. Recent results,
      however, clearly indicate that opioids play a specific role in skin homeostasis
      by modulating keratinocyte differentiation, wound healing, and inflammatory
      responses.

PMID- 17502860
TI  - Clues from alopecia areata on the role of neuropeptides in the initiation of
      autoimmunity.
AB  - A fascinating question regarding the pathogenesis of alopecia areata is the
      potential linkage with the brain. Siebenharr et al. demonstrate that substance P
      fibers are increased in early lesions, and that substance P treatment induces
      catagen follicles along with activated CD8+ T cells. Potentially, neuropeptides
      serve as the initial insult resulting in loss of tolerance and autoimmune
      disease.

PMID- 17502861
TI  - Tumor necrosis factor blockade: mechanism of action.
AB  - Modulation of the immune response with tumor necrosis factor (TNF) blockers is
      not a new treatment strategy for many inflammatory disorders; however, relatively
      little is known about their specific mechanism of action. Understanding the mode
      of action, pharmacology, and pharmacokinetics of the monoclonal TNF antibodies,
      infliximab and adalimumab, and the soluble TNF receptor, etanercept, may
      therefore enable us to account for their differing clinical profiles. The aim of
      this supplement is to explore the roles and mechanisms of TNF and TNF blockade
      using in vitro pharmacological and in vivo animal modeling experiments, and in
      vivo studies of the effects of etanercept on the inflammatory cascade in patients
      with psoriasis.

PMID- 17502862
TI  - Binding characteristics of tumor necrosis factor receptor-Fc fusion proteins vs
      anti-tumor necrosis factor mAbs.
AB  - Tumor necrosis factor (TNF) antagonists are efficacious in the treatment of
      various autoimmune diseases. Two classes of TNF antagonists are currently
      commercially available: soluble TNF receptor-Fc fusion proteins (etanercept) and
      anti-TNF mAbs (adalimumab and infliximab). The classes differ in molecular
      structures and mechanisms of action. The interactions between TNF antagonists
      with TNF molecules were characterized. The anti-TNF mAbs, but not the soluble TNF
      receptor, formed visible lines of precipitation in Ouchterlony assays. The
      molecular weights of complexes formed by TNF (52 kDa) with either etanercept (130
      kDa), adalimumab (150 kDa), or infliximab (average 165 kDa) were determined by
      size exclusion chromatography-light-scattering assays. Etanercept and TNF formed
      complexes of 180 and 300 kDa, representing one and two etanercept monomers bound
      to a TNF trimer, respectively. Adalimumab and infliximab formed a variety of
      complexes with TNF with molecular weights as high as 4,000 and 14,000 kDa,
      respectively, suggesting the presence of complexes with a wide range of sizes and
      stoichiometries. The absence of large complex formation with the binding of
      soluble receptor-fusion proteins to TNF may account for the different clinical
      efficacy and safety profiles of the two classes of TNF antagonists.

PMID- 17502863
TI  - Effects of etanercept are distinct from infliximab in modulating proinflammatory
      genes in activated human leukocytes.
AB  - Proinflammatory diseases like rheumatoid arthritis, Crohn's disease, and
      psoriasis have been treated by the tumor necrosis factor (TNF) antagonists
      infliximab and etanercept with different degrees of success. Although these
      agents are widely used in humans, little is known about their mechanisms of
      action or why etanercept and infliximab have differences in clinical activity. In
      this study, we define leukocyte genes that are suppressed by etanercept within 24
      hours of exposure. Compared to previous work with infliximab, fewer immune
      related genes are suppressed by etanercept. Importantly, the range of genes
      suppressed by these alternative TNF inhibitors is only partially overlapping,
      suggesting each has unique immune modulating effects. In sharp contrast to
      etanercept, infliximab strongly suppresses genes associated with "Type 1" immune
      responses (IFN-gamma and the IL-12-receptor beta 2 subunit), providing a clear
      mechanism for clinically relevant immune suppression.

PMID- 17502864
TI  - Reactivation of latent tuberculosis by TNF blockade: the role of interferon
      gamma.
AB  - Tumor necrosis factor (TNF) plays a pathogenic role in psoriasis and rheumatoid
      arthritis but is essential for host defenses against mycobacteria and other
      granulomatous pathogens. The risk of reactivation of latent Mycobacterium
      tuberculosis infection is significantly greater with the TNF monoclonal antibody
      infliximab than with the soluble TNF-receptor etanercept. We have examined the
      biologic basis of this difference using whole blood culture. Infliximab and
      adalimumab reduced the proportion of T buciclate-responsive cells by 70 and 50%,
      respectively, and suppressed antigen-induced IFN-gamma production by 70 and 64%.
      In contrast, etanercept produced no significant effect. The difference between
      infliximab and etanercept remained whether one compared equal or peak therapeutic
      drug concentrations, suggesting a relationship to mechanism of action rather than
      pharmacokinetics. Adalimumab and etanercept caused divergent, concentration
      dependent effects on control of intracellular growth of M. tuberculosis. None of
      the drugs induced significant levels of apoptosis or necrosis in monocytes or T
      cells, excluding T-cell death as a mechanism for suppression of antigen-induced
      responses. IL-10 production was equally suppressed by all three drugs, excluding
      excess IL-10 as a regulatory mechanism. The tuberculosis risk posed by infliximab
      may reflect its combined effects on TNF and IFNgamma.

PMID- 17502865
TI  - Tumor necrosis factor and tuberculosis.
AB  - Tumor necrosis factor (TNF) plays a major role in the initial and long-term
      control of tuberculosis. The mechanisms by which this cytokine contributes to the
      control of Mycobacterium tuberculosis infection are numerous and therefore
      difficult to dissect. TNF is important in macrophage activation as well as cell
      recruitment to the site of infection. It is the primary signal important in
      granuloma formation, as neutralization of this cytokine leads to lack of control
      of initial or chronic infection, and loss of granuloma structure. In humans
      treated with TNF-neutralizing drugs, an increased susceptibility to tuberculosis,
      as well as other infectious diseases, is observed. We are using animal models to
      understand how TNF neutralization by these drugs can lead to reactivation of
      tuberculosis.

PMID- 17502866
TI  - Mycobacterium tuberculosis-induced cell death of primary human monocytes and
      macrophages is not significantly modulated by tumor necrosis factor-targeted
      biologicals.
AB  - Differential induction of cell death in mycobacteria-infected monocytes and
      macrophages has been invoked as one possible mechanism by which some tumor
      necrosis factor (TNF)-targeted biologicals reactivate tuberculosis more
      frequently than others. We infected primary human monocytes and monocyte-derived
      macrophages with the virulent Mycobacterium tuberculosis strain H37Rv and
      followed the rate of cell death in the absence or presence of a wide
      concentration range of four different TNF-targeted biologicals: infliximab and
      adalimumab (both monoclonal antibodies to human TNF) and etanercept and
      polyethylene-glycols TNFR1 (fusion constructs of human TNFR2 and TNFR1,
      respectively). None of the TNF-targeted biologicals used modulated the death rate
      of monocytes/macrophages induced by infection with M. tuberculosis alone. Our
      data support the view that mycobacteria-induced cell death is largely independent
      of TNF and that the primary target for differential modulation by TNF-targeted
      biologicals during tuberculosis is not a recently recruited monocyte or freshly
      differentiated macrophage.

PMID- 17502867
TI  - Tumor necrosis factor-alpha and host resistance to the pathogenic fungus,
      Histoplasma capsulatum.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that is
      critically important in host defenses to a number of pathogenic microbes. Among
      those, this cytokine is necessary for control of infection with the pathogenic
      fungus, Histoplasma capsulatum. Antagonism of endogenous cytokine is associated
      with an enhanced susceptibility to histoplasmosis in both mice and humans. The
      mechanisms by which TNF-alpha modulates the protective immune response will be
      discussed.

PMID- 17502868
TI  - Mechanisms of action of etanercept in psoriasis.
AB  - Psoriasis is a chronic inflammatory disease of the skin affecting up to 2.5% of
      the world's population. The scaly, erythematous plaques characteristic of this
      papulosquamous disorder are likely triggered and maintained by cytokines and
      chemokines manufactured by cells of the immune system. Overproduction of
      inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and IFN
      gamma, results in a self-sustaining inflammatory cascade, causing abnormal
      keratinocyte proliferation and differentiation. Therapeutic drug design targeting
      TNF has led to the emergence of successful biologic agents, such as etanercept,
      in recent years. Despite extensive clinical trials documenting efficacious
      clinical response to therapy, there is a paucity of data investigating the
      molecular mechanisms by which etanercept modulates the improvement of psoriasis.
      This brief review summarizes recent work investigating the in vivo actions of
      etanercept, including its effects on various cell types, inflammatory pathways,
      gene activation, nuclear factor kappa B expression, and apoptosis. The anti
      inflammatory properties of etanercept reveal mechanisms by which a TNF blockade
      may result in the improvement of psoriasis.

PMID- 17502869
TI  - Structural-functional relationships of TNF-alpha antagonists: next steps.
AB  - The balance between effective tumor necrosis factor (TNF) blockade to control
      aggressive autoimmune disease states and adequate remaining TNF activity to
      confer immunoprotection against infections such as tuberculosis is an important
      and complex issue. An increased scientific understanding of how each of the TNF
      antagonist agents affects the complex interactions of the inflammation cascade
      and apoptosis, and whether the effects are modulatory or destructive, is needed.
      The data presented in this supplement highlight the need for further research
      into these key areas, and illustrate our current understanding of the mode of
      action of TNF blockers as only the tip of the iceberg.

PMID- 17502870
TI  - Construction and purification of the murine p75-murine IgG1 fusion protein.
AB  - Etanercept (Amgen Inc, Thousand Oaks, CA) is a human soluble p75 tumor necrosis
      factor (TNF) receptor-human-IgG1 (hup75 TNFR-huIgG1) fusion protein used in the
      treatment of chronic inflammatory diseases in humans, including rheumatoid
      arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, psoriatic
      arthritis, and psoriasis. To be able to study the effects of the soluble receptor
      fusion protein in mouse models, including those that mimic human granulomatous
      infections, a murine soluble p75-TNF receptor-murine IgG1 (murine p75-murine
      IgG1) fusion protein had to be constructed. This article discusses the
      generation, large-scale production, and purification of this molecule.

PMID- 17502871
TI  - Pharmacodynamic effects of the murine p75-Fc fusion protein in mice.
AB  - Overproduction of inflammatory mediators, such as tumor necrosis factor (TNF), is
      key to the development and maintenance of inflammatory processes. Etanercept is a
      soluble TNF receptor fusion protein used in the treatment of various chronic
      inflammatory diseases, including rheumatoid arthritis and psoriasis. This study
      investigated the effects of murine p75-Fc, a soluble TNF receptor protein, on TNF
      induced IL-6 production in mice. Six groups of mice received either murine p75-Fc
      (0.15, 0.50, 1.5, 5, and 15 mg/kg) or phosphate-buffered saline. Three days
      later, mice were injected intravenously with 10 microg of murine TNF and blood
      samples were taken after 3 hours. Serum IL-6 and TNF were measured by ELISA. Mice
      treated with 5 and 15 mg/kg murine p75-Fc demonstrated complete inhibition of TNF
      induced IL-6 production. Murine p75-Fc (1.5 mg/kg) resulted in a partial but
      significant reduction of TNF-induced IL-6 production. No TNF was detected in 5
      and 15 mg/kg murine p75-Fc-treated mice, except one in the 5 mg/kg dose group. In
      conclusion, murine p75-Fc completely inhibits TNF-induced IL-6 production in
      mice.

PMID- 17502872
TI  - Pharmacokinetics of murine p75-Fc fusion protein and MP6-XT22 anti-murine TNF
      alpha mAb in mice.
AB  - Immunologic limitations make it difficult to study the pharmacokinetic effects of
      human tumor necrosis factor (TNF) blockers in murine models. To counter this, we
      have studied the pharmacokinetics in mice of two murine analogs of human TNF
      blockers, a murine p75-FC fusion protein (analogous to etanercept), and the rat
      MP6-XT22 anti-murine TNF mAb (analogous to infliximab). We analyzed the
      pharmacokinetics of the murine p75-Fc protein and MP6-XT22 antibody in mice that
      were uninfected and in mice with disseminated candidiasis in order to confirm
      dosing strategies and interpret future studies evaluating the efficacy and
      tolerability of these agents in mice. We propose that, while conducting safety or
      efficacy studies in murine disease models, it is reasonable to administer the
      murine p75-Fc protein to mice at <10 mg/kg every 4-5 days, and the MP6-XT22
      antibody at 10-20 mg/kg every 4-5 days.

PMID- 17502873
TI  - UCP2 A55V variant is associated with obesity and related phenotypes in an
      aboriginal community in Taiwan.
AB  - OBJECTIVE: Human uncoupling proteins 2 and 3 (UCP2 and UCP3) are two
      mitochondrial proteins that are involved in the control of metabolism of fatty
      acid and possibly protect against oxidative damage. The aim of this study was to
      analyze genetic associations of four polymorphisms of the UCP2 and UCP3 genes
      with insulin, leptin concentration and obesity in Taiwan aborigines. RESEARCH
      METHODS: Four polymorphisms were compared in 324 obese (body mass index (BMI) >
      or =30 kg/m(2)) and overweight (30>BMI > or =25 kg/m(2)) subjects, and 114 normal
      weight subjects (BMI <25 kg/m(2)) in an aboriginal community of southern Taiwan.
      Anthropometric characteristics and fasting levels of insulin, leptin,
      triglycerides and cholesterol were measured. RESULTS: Before and after adjusting
      for age distribution, only the Val55 allele in exon 4 of the UCP2 gene increased
      the risk of overweight and obesity (adjusted odds ratio (OR)=2.02, P=0.004) in
      comparison with Ala55. UCP2 V55V is also associated with higher fasting insulin
      levels than A55V (P=0.01) and A55A (P=0.04) in the obese/overweight group. Using
      the COCAPHASE program of the UNPHASED software, haplotype analysis of three
      single nucleotide polymorphisms (A55V-G866A-C-55T) revealed that A-G-C (73% in
      obese subjects and 77% in controls) was the most common haplotype and that the
      haplotype V-A-T (13% in obese subjects and 5% in controls) was significantly
      increased in obese and overweight subjects (BMI > or =25 kg/m(2)) (OR=2.62,
      P<0.001). DISCUSSIONS: UCP2 A55V variant might predispose to obesity and Val55
      allele to confer population-attributable risk for 9.5% of obese disorders and
      increase insulin concentrations. The V-A-T haplotype within UCP2-UCP3 gene
      cluster is also significantly associated with obesity in Paiwan aborigines.

PMID- 17502874
TI  - Randomized trial of weight-loss-diets for young adults varying in fish and fish
      oil content.
AB  - OBJECTIVE: To investigate the effect of including seafood and fish oils, as part
      of an energy-restricted diet, on weight loss in young overweight adults. DESIGN:
      Randomized controlled trial of energy-restricted diet varying in fish and fish
      oil content was followed for 8 weeks. Subjects were randomized to one of four
      groups: (1) control (sunflower oil capsules, no seafood); (2) lean fish (3 x 150
      g portions of cod/week); (3) fatty fish (3 x 150 g portions of salmon/week); (4)
      fish oil (DHA/EPA capsules, no seafood). The macronutrient composition of the
      diets was similar between the groups and the capsule groups, were single-blinded.
      SUBJECTS: A total of 324 men and women aged 20-40 years, BMI 27.5-32.5 kg/m(2)
      from Iceland, Spain and Ireland. MEASUREMENTS: Anthropometric data were collected
      at baseline, midpoint and endpoint. Confounding factors were accounted for, with
      linear models, for repeated measures with two-way interactions. The most
      important interactions for weight loss were (diet x energy intake), (gender x
      diet) and (gender x initial-weight). RESULTS: An average man in the study (95 kg
      at baseline receiving 1600 kcal/day) was estimated to lose 3.55 kg (95% CI, 3.14
      3.97) (1); 4.35 kg (95% CI, 3.94-4.75) (2); 4.50 kg (95% CI, 4.13-4.87) (3) and
      4.96 kg (95% CI, 4.53-5.40) on diet (4) in 4 weeks, from baseline to midpoint.
      The weight-loss from midpoint to endpoint was 0.45 (0.41-0.49) times the observed
      weight loss from baseline to midpoint. The diets did not differ in their effect
      on weight loss in women. Changes in measures of body composition were in line
      with changes in body weight. CONCLUSION: In young, overweight men, the inclusion
      of either lean or fatty fish, or fish oil as part of an energy-restricted diet
      resulted in approximately 1 kg more weight loss after 4 weeks, than did a similar
      diet without seafood or supplement of marine origin. The addition of seafood to a
      nutritionally balanced energy-restricted diet may boost weight loss.

PMID- 17502875
TI  - Early growth response gene 1 (Egr-1) regulates HSV-1 ICP4 and ICP22 gene
      expression.
AB  - The molecular mechanisms mediating herpes simplex virus type 1 (HSV-1) gene
      silencing during latent infection are not clear. Five copies of early growth
      response gene 1 (Egr-1) binding elements were identified in the intron of HSV-1
      ICP22 (infected cell protein No. 22) gene, leading to the hypothesis that Egr-1
      binds to the viral genome and regulates the viral gene expression. Transient co
      transfection assays indicated that Egr-1 negatively regulated the transcription
      of both full-length and intron-removed ICP22 promoters. The same assays also
      revealed that Egr-1 repressed ICP4 (infected cell protein No. 4) promoter
      activity in a dose-dependent manner but showed less inhibition when the intron
      was removed. Histone deacetylation was not involved in this regulation since
      histone deacetylase inhibitor trichostatin A did not exhibit any effect on Egr-1
      mediated repression. Chromatin immunoprecipitation assays showed that Egr-1
      reduced the binding of Sp1 to the promoters and that the co-repressor Nab2 (NGFI
      A/EGR1-binding protein) was recruited to the proximity of ICP4 in the presence of
      Egr-1. These results suggested that the multifunctional transcription factor Egr
      1 can repress HSV-1 immediate-early gene expression through the recruitment of co
      repressor Nab2 and reduction of Sp1 occupancy, and thus may play a critical role
      in HSV-1 gene silencing during latency.

PMID- 17502876
TI  - Electroencephalographic slowing and reduced reactivity in neuropathic pain
      following spinal cord injury.
AB  - STUDY DESIGN: Brain wave activity in people with paraplegia, with and without
      neuropathic pain, was compared to brain wave activity in matched able-bodied
      controls. OBJECTIVES: To investigate whether spinal cord injury with neuropathic
      pain is associated with a slowing of brain wave activity. SETTING: Australia.
      METHODS: Electroencephalographic (EEG) data were collected in the eyes open (EO)
      and eyes closed (EC) states from 16 participants with paraplegia (eight with
      neuropathic pain and eight without pain) and matched able-bodied controls. Common
      EEG artefacts were removed using independent component analysis (ICA). Peak
      frequency in the theta-alpha band and EEG power in the delta, theta, alpha and
      beta frequency bands were compared between groups. RESULTS: The results show
      significant slowing of the EEG in people with neuropathic pain, consistent with
      the presence of thalamocortical dysrhythmia (TCD). Furthermore, people with
      neuropathic spinal cord injury (SCI) pain had significantly reduced EEG spectral
      reactivity in response to increased or decreased sensory input flowing into the
      thalamocortical network, as modulated by the eyes open and eyes closed states.
      CONCLUSION: The results provide further evidence for alterations in brain
      electric activity that may underlie the development of neuropathic pain following
      SCI.

PMID- 17502877
TI  - The association between regional body composition and metabolic outcomes in
      athletes with spinal cord injury.
AB  - STUDY DESIGN: Cross-sectional study comparing athletes with spinal cord injury
      (SCI) and age and body mass index matched able-bodied controls (AB). OBJECTIVE:
      To examine the impact of exercise training on the relation between whole body,
      regional and intermuscular adipose tissue (IMAT) and glucose tolerance, insulin
      action and lipid profile. SETTING: University Research Laboratory, USA. METHODS:
      Fourteen college-aged athletes with SCI (seven men; duration of injury 16.5+/-5.7
      years, level of injury T5-L5) and 17 sedentary AB (eight men) were assessed for
      body composition via dual-energy X-ray absorptiometry (DXA) and magnetic
      resonance imaging. Insulin sensitivity index (ISI) was determined via 2-h oral
      glucose challenge; standard lipid profile was determined from fasting blood
      samples. RESULTS: Although ISI was 30% higher in SCI, there were no significant
      differences between groups in glucose and insulin responses or in lipid measures.
      Adjusting for absolute and relative thigh IMAT area, fasting insulin (13.8+/-5.3
      microIU, 16.3+/-5.6 microIU; P<0.05; SCI vs AB respectively) and ISI (4.0+/-1.4,
      3.1+/-1.3; P<0.05) were significantly better among SCI athletes compared to AB.
      Measures of adiposity did not correlate with glucose response or most lipid
      measures. Within SCI and AB, respectively, ISI correlated strongly (all P<0.05)
      with absolute (r = -0.70, -0.54) and relative IMAT (r = -0.54, -0.50), than with
      trunk (r = -0.62, -0.64) and whole body fat mass (r = -0.61, -0.64). CONCLUSION:
      Habitual physical activity can maintain insulin sensitivity in SCI compared to
      sedentary AB controls. Total body fat mass, central adiposity and thigh IMAT
      appear to impact risk for metabolic disease in SCI individuals with IMAT playing
      a larger role in SCI than AB.

PMID- 17502878
TI  - Validation of the walking index for spinal cord injury in a US and European
      clinical population.
AB  - OBJECTIVE: To demonstrate the prospective construct validity of the walking index
      for spinal cord injury (WISCI) in US/European clinical population. DESIGN:
      Prospective Cohort in Denmark, Germany, Italy and the USA. PARTICIPANTS/METHOD:
      Participants with acute complete/incomplete (ASIA Impairment Scale (AIS) A, B, C
      and D) traumatic spinal cord injuries were enrolled from four centers. Lower
      extremity motor scores (LEMS), WISCI level and Locomotor Functional Independence
      Measure (LFIM) levels were assessed with change in ambulatory status. WISCI
      progression was assessed for monotonic direction of improvement (MDI). LEMS were
      correlated to WISCI/LFIM. Use of walking aids/braces were analyzed. RESULTS: One
      hundred and seventy participants were enrolled and 20 excluded. Of the 150
      participants (USA 112/150; Europe 38/150) (AIS A=59, B=19, C=32, D=40), LEMS and
      WISCI assessments were performed initially and at final assessment (3-12 months
      post injury) or until maximum WISCI score of 20. Eighty-five percent of motor
      complete (66/78) and 10% (7/72) of motor incomplete participants showed no
      progression (73/150). Of the remaining participants (77/150) who improved, 81%
      (62/77) showed MDI. However, the deviation from MDI occurred only at one time
      point in 10/15 participants. LEMS correlated with WISCI at initial and final
      assessment (0.47 and 0.91 P<0.001). Parallel bar use differed between the US and
      Europe possibly due to patterns of care. Use of braces also differed. CONCLUSION:
      The results support the hierarchical ranking of the WISCI scale and the
      correlation of WISCI levels to impairment (LEMS) in a clinical setting of four
      nations. Differences in practice between the US and Europe need consideration in
      design of trials.

PMID- 17502879
TI  - Does adherence to medical therapy improve long-term survival after myocardial
      infarction?

PMID- 17502880
TI  - Should all patients with suspected stroke have brain MRI instead of CT?

PMID- 17502881
TI  - Ovulation induction in polycystic ovary syndrome-how do metformin and clomifene
      citrate compare?

PMID- 17502882
TI  - Is it necessary to endoscopically screen all patients with hepatitis C and
      advanced fibrosis for esophageal varices?

PMID- 17502883
TI  - Do all patients with pancreatic cysts need to undergo resection or can some be
      monitored?

PMID- 17502884
TI  - Steroid withdrawal in African American kidney transplant recipients: long-term
      effects on graft outcomes.

PMID- 17502885
TI  - Infusing vasopressin to prevent intradialytic hypotension.

PMID- 17502886
TI  - Are the effects of prolonged cold ischemia a barrier to long-distance
      transportation of living donor kidneys?

PMID- 17502887
TI  - Is lenalidomide a new standard treatment for myelodysplastic syndrome?

PMID- 17502888
TI  - Is anti-tumor necrosis factor therapy effective in reducing uveitis flares in
      patients with spondyloarthropathies?

PMID- 17502889
TI  - How prevalent is neobladder emptying failure, and how can it be treated?

PMID- 17502890
TI  - Which BPH treatment is the most clinically efficacious and cost-effective?

PMID- 17502891
TI  - Immune-mediated motor polyneuropathy after hematopoietic stem cell
      transplantation.

PMID- 17502892
TI  - Successful mobilization of peripheral blood stem cells in an acute promyelocytic
      leukemia patient after gemtuzumab ozogamicin.

PMID- 17502893
TI  - First report of successful stem cell transplantation in a child with CD40
      deficiency.

PMID- 17502894
TI  - Central nervous system graft-versus-host disease presenting with granulomatous
      encephalitis.

PMID- 17502895
TI  - Chimerism does not predict for outcome after alemtuzumab based conditioning.

PMID- 17502896
TI  - Long-term graft-versus-Waldenstrom macroglobulinemia effect following reduced
      intensity conditioning allogeneic stem cell transplantation.

PMID- 17502897
TI  - Prophylactic defibrotide in allogeneic stem cell transplantation: minimal
      morbidity and zero mortality from veno-occlusive disease.
AB  - Veno-occlusive disease (VOD) is a common and high-risk complication of allogeneic
      stem cell transplantation (SCT). Defibrotide has recently been used successfully
      to treat the disorder. We report on 58 patients who received defibrotide
      prophylaxis without concurrent heparin. No patients fulfilled the Baltimore
      criteria for VOD or died of the condition within 100 days of SCT. None of this
      group developed haemorrhagic complications secondary to defibrotide. These
      observations suggest that prophylaxis with defibrotide alone may reduce the
      incidence of VOD post-SCT although a randomised controlled trial is warranted to
      further evaluate its role.

PMID- 17502898
TI  - T cell therapies following hematopoietic stem cell transplantation: surely there
      must be a better way than DLI?
AB  - Advances in the past few years have significantly improved adoptive immunotherapy
      strategies available following autologous and allogeneic hematopoietic stem cell
      transplantation (HSCT). Minimal residual disease, relapsed disease and viral
      infections remain a significant cause of mortality in patients undergoing HSCT.
      Novel therapies are critically needed to overcome these management dilemmas,
      while sparing the graft-versus-tumor effect and avoiding graft-versus-host
      disease. This review focuses on the T-cell strategies currently available to
      allay disease while minimizing toxicities in patients who have undergone HSCT.

PMID- 17502899
TI  - STS markers for the wheat yellow rust resistance gene Yr5 suggest a NBS-LRR-type
      resistance gene cluster.
AB  - Two sequence-tagged site (STS) markers for the wheat yellow rust resistance (R)
      gene Yr5 have been derived through the identification and characterization of
      linked amplified fragment length polymorphisms (AFLPs). The sequences of the 2
      AFLP markers partially overlap with one another, but belong to discrete loci:
      S19M93-140 completely cosegregates with Yr5, whereas S23M41-310 maps at a
      distance of 0.7 cM. The DNA sequence of S23M41-310 shows significant homology
      with the 3' end of nucleotide-binding site (NBS) - leucine-rich repeat (LRR) -
      type R-genes, in particular with orthologues of the rice bacterial blight R-gene
      Xa-I. The distinct genetic location of the 2 AFLP loci suggests that Yr5 falls
      within an R-gene cluster. Because neither sequence forms part of a detectable
      transcription product, we propose that the Yr5 R-gene cluster includes R-gene
      analogues and pseudogenes. A Yr5 flanking simple sequence repeat (SSR) marker has
      also been identified, which allows Yr5 to be effectively incorporated, along with
      other R-genes for yellow rust, into elite wheat genetic backgrounds, through
      marker-assisted selection.

PMID- 17502900
TI  - Development, characterization, and comparative analysis of polymorphism at common
      bean SSR loci isolated from genic and genomic sources.
AB  - Microsatellites or SSRs (single sequence repeats) have been used to construct and
      integrate genetic maps in crop species, including Phaseolus vulgaris. In the
      present study, 3 cDNA libraries generated by the Bean EST project
      (http://lgm.esalq.usp.br/BEST/), comprising a unigene collection of 3126
      sequences and a genomic microsatellite-enriched library, were analyzed for the
      presence of SSRs. A total of 219 expressed sequence tags (ESTs) were found to
      carry 240 SSRs (named EST-SSR), whereas 714 genomic sequences contained 471 SSRs
      (named genomic-SSR). A subset of 80 SSRs, 40 EST-SSRs, and 40 genomic-SSRs were
      evaluated for molecular polymorphism in 23 genotypes of cultivated beans from the
      Mesoamerican and Andean genetic pools, including Brazilian cultivars and 2
      related species. Of the common bean genotypes, 31 EST-SSR loci were polymorphic,
      yielding 2-12 alleles as compared with 26 polymorphic genomic-SSRs, accounting
      for 2-7 alleles. Cluster analysis from data using both genic and genomic-SSR
      revealed a clear separation between Andean and Mesoamerican beans. The usefulness
      of these loci for distinguishing bean genotypes and genetic mapping is discussed.

PMID- 17502901
TI  - A plant-transformation-competent BIBAC/BAC-based map of rice for functional
      analysis and genetic engineering of its genomic sequence.
AB  - Sequencing of the rice genome has provided a platform for functional genomics
      research of rice and other cereal species. However, multiple approaches are
      needed to determine the functions of its genes and sequences and to use the
      genome sequencing results for genetic improvement of cereal crops. Here, we
      report a plant-transformation-competent, binary bacterial artificial chromosome
      (BIBAC) and bacterial artificial chromosome (BAC) based map of rice to facilitate
      these studies. The map was constructed from 20 835 BIBAC and BAC clones, and
      consisted of 579 overlapping BIBAC/BAC contigs. To facilitate functional analysis
      of chromosome 8 genomic sequence and cloning of the genes and QTLs mapped to the
      chromosome, we anchored the chromosomal contigs to the existing rice genetic
      maps. The chromosomal map consists of 11 contigs, 59 genetic markers, and 36
      sequence tagged sites, spanning a total of ca. 38 Mb in physical length.
      Comparative analysis between the genetic and physical maps of chromosome 8 showed
      that there are 3 "hot" and 2 "cold" spots of genetic recombination along the
      chromosomal arms in addition to the "cold spot" in the centromeric region,
      suggesting that the sequence component contents of a chromosome may affect its
      local genetic recombination frequencies. Because of its plant transformability,
      the BIBAC/BAC map could provide a platform for functional analysis of the rice
      genome sequence and effective use of the sequencing results for gene and QTL
      cloning and molecular breeding.

PMID- 17502902
TI  - Estimating a founder's genomic proportion for each descendant in an outbred
      pedigree.
AB  - The question of how to estimate a founder's proportion of a single descendant's
      genome has renewed relevance for outbred pedigrees, given the abundant DNA
      sequence data for model and nonmodel eukaryotes alike. Here we show that a donor
      recurrent shortcut method can provide a robust estimation of founder proportions.
      In addition, we define the theoretical variance and estimate confidence intervals
      using a nonparameteric bootstrap method. Using actual marker data from a highly
      heterozygous outbred Pinus taeda pedigree, it was found that each founder's
      genomic proportion varied widely for each descendant, ranging from 8.8% to 38.7%.
      In 1 case, skewed transmission of a founder's genome could be statistically
      detected. Its founder proportions ranged from 1.54% to 48.46%, and its mean value
      was 17.59%, well below the expected value of 25%. Two-thirds of its 91
      descendants had 1 or the other founder haplotype, despite 2 successive meioses.
      The donor-recurrent method was robust; variation for estimated founder's
      proportions was also wide for simulated high-density datasets whether markers
      were dispersed or clustered. Estimating founder contributions using this
      computational shortcut has broad application for highly heterozygous outbred
      pedigrees characterized by large sibships, low population differentiation, and
      shallow physical mapping resources. The relevance of this computational shortcut
      for outbred populations used for conservation, domestication, and evolutionary
      biology research is discussed.

PMID- 17502903
TI  - Genome-wide high-frequency non-Mendelian loss of heterozygosity in rice.
AB  - Classic Mendelian genetics declares that hybrids inherit genomic information from
      both male and female parents, and that alleles should be heterozygous in F1
      plants. A few exceptions to this principle have been reported, but most of them
      are restricted to either a limited set of specific genes or specific types of
      alleles. Here, we show that a rice triploid and diploid hybridization resulted in
      stable diploid progenies, both in genotypes and phenotypes, through gene
      homozygosity. Furthermore, their gene homozygosity can be inherited through 8
      generations, and they can convert DNA sequences of other rice varieties into
      their own. Molecular-marker examination confirmed that this type of genome-wide
      gene conversion occurred at a very high frequency. Possible mechanisms, including
      RNA-templated repair of double-strand DNA, are discussed.

PMID- 17502904
TI  - Quantitative genetic analysis of flowering time in tomato.
AB  - Artificial selection of cultivated tomato (Solanum lycopersicum L.) has resulted
      in the generation of early-flowering, day-length-insensitive cultivars, despite
      its close relationship to other Solanum species that need more time and specific
      photoperiods to flower. To investigate the genetic mechanisms controlling
      flowering time in tomato and related species, we performed a quantitative trait
      locus (QTL) analysis for flowering time in an F2 mapping population derived from
      S. lycopersicum and its late-flowering wild relative S. chmielewskii. Flowering
      time was scored as the number of days from sowing to the opening of the first
      flower (days to flowering), and as the number of leaves under the first
      inflorescence (leaf number). QTL analyses detected 2 QTLs affecting days to
      flowering, which explained 55.3% of the total phenotypic variance, and 6 QTLs for
      leaf number, accounting for 66.7% of the corresponding phenotypic variance. Four
      of the leaf number QTLs had not previously been detected for this trait in
      tomato. Colocation of some QTLs with flowering-time genes included in the genetic
      map suggests PHYB2, FALSIFLORA, and a tomato FLC-like sequence as candidate genes
      that might have been targets of selection during the domestication of tomato.

PMID- 17502905
TI  - Introgressive hybridization between the allotetraploid Coffea arabica and one of
      its diploid ancestors, Coffea canephora, in an exceptional sympatric zone in New
      Caledonia.
AB  - The importance of introgressive hybridization in plant evolution has long been
      recognized. Nevertheless, information on gene flow between allopolyploids and
      their diploid relatives is very limited, even though gene flow could play a major
      role in polyploid establishment and evolution. Here, we investigated the
      processes governing hybrid formation and introgression between the allotetraploid
      Coffea arabica and one of its ancestral diploid progenitors, C. canephora, in a
      sympatric zone of New Caledonia. The occurrence of a large assortment of
      hybridization events between the 2 coffee species is clearly established. First
      generation hybrids (F1) and post-F1 hybrids were characterized. The involvement
      of unreduced gametes of C. canephora is suggested, because tetraploid F1 hybrid
      plants were detected. Moreover, although bidirectional mating was observed, only
      unidirectional gene flow from C. canephora to C. arabica was noted in post-F1
      hybrids. Most of the collected post-F1 hybrid plants exhibited a high level of
      introgression, and the frequency of introgression observed among the different
      analyzed loci was homogeneous, suggesting no significant counterselection against
      introgressions from C. canephora. Overall, the New Caledonian central mountains
      appear to be a highly favourable environment for introgressive hybridization and
      a genetic diversity center for C. arabica.

PMID- 17502906
TI  - 'Cardinal' grape parentage: a case of a breeding mistake.
AB  - The grapevine (Vitis vinifera L.) is one of the most widely grown fruit plants,
      with table grapes accounting for at least 20% of the total world production. A
      few traditional table grape cultivars have achieved great international
      prominence. Among the most important cultivars is 'Cardinal', a historical
      Californian grapevine obtained by E. Snyder and F. Harmon in 1939 by crossing
      'Flame Tokay' (syn. 'Ahmer Bou Amer') with 'Ribier' (syn. 'Alphonse Lavallee') at
      the Horticultural Field Station of Fresno, Calif.. In the course of DNA typing
      grapevine varieties collected in Algeria and other Mediterranean countries, we
      found, surprisingly, that 'Cardinal'could not result from this cross. Here, we
      present molecular genetic evidence that 'Cardinal' has no parentage relationship
      with 'Flame Tokay'. We also show, for the first time, that 'Flame Tokay' is a
      mutant version, at the VVS5 microsatellite locus, of the table grape 'Ahmer Bou
      Amer', which is considered its synonym.

PMID- 17502907
TI  - Development and characterization of 248 novel microsatellite markers in turbot
      (Scophthalmus maximus).
AB  - The turbot is a flatfish species of great relevance to marine aquaculture in
      Europe. Only a limited number of microsatellites have been isolated to date in
      this species. To increase the number of potentially useful mapping markers, we
      screened simple sequence repeat (SSR)--enriched genomic libraries obtained from
      several di-, tri-, and tetranucleotide tandem repeat motifs. A total of 248 new
      polymorphic microsatellites were successfully optimized. The efficiency of the
      protocol applied (6.4%) was higher than that in other studies of fish that used
      the same method. Dinucleotide and perfect microsatellites were predominant in
      this species; the (AC)n motif was the most frequent class of repeat. Polymorphism
      and structural properties at these loci, together with 30 variable loci
      previously reported in turbot, were evaluated in 6 wild individuals. The number
      of alleles per locus ranged from 2 to 10, with an average of 4.046. The
      microsatellite markers characterized in this study will contribute to the
      development of the turbot genetic map, which can be used for quantitative trait
      locus (QTL) identification, marker-assisted selection programs, and other
      applications to improve its culture.

PMID- 17502908
TI  - Inhibition of hippocampal matrix metalloproteinase-3 and -9 disrupts spatial
      memory.
AB  - Memory consolidation requires synaptic reconfiguration dependent upon
      extracellular matrix (ECM) molecules interacting with cell adhesion molecules.
      Matrix metalloproteinase (MMP) activity is responsible for transient alterations
      in the ECM that may be prerequisite to hippocampal-dependent learning. In support
      of this hypothesis we have measured increases in MMP-3 and MMP-9 levels within
      the hippocampus and prefrontal cortex during Morris water maze training. The
      present investigation extends these findings by determining that infusion of an
      MMP inhibitor (FN-439) into the dorsal hippocampus disrupted acquisition of this
      task. In vitro fluorescence enzyme assays to determine the specificity of FN-439
      against the catalytic domains of MMP-3 and MMP-9 indicated mean +/- SEM IC(50)s
      of 16.2 +/- 7.8 and 210.5 +/- 37.8 muM, respectively, while in situ zymography
      using hippocampal sections treated with FN-439 indicated significant reductions
      in MMP gelatinase activity. These results suggest that compromising the ability
      of the dorsal hippocampus to reconfigure ECM molecules by inhibiting MMP activity
      interferes with appropriate spatial memory acquisition, and support a role for
      hippocampal MMPs in the phenomena of spatial memory acquisition and storage.

PMID- 17502909
TI  - The role of the medial prefrontal cortex-amygdala circuit in stress effects on
      the extinction of fear.
AB  - Stress exposure, depending on its intensity and duration, affects cognition and
      learning in an adaptive or maladaptive manner. Studies addressing the effects of
      stress on cognitive processes have mainly focused on conditioned fear, since it
      is suggested that fear-motivated learning lies at the root of affective and
      anxiety disorders. Inhibition of fear-motivated response can be accomplished by
      experimental extinction of the fearful response to the fear-inducing stimulus.
      Converging evidence indicates that extinction of fear memory requires plasticity
      in both the medial prefrontal cortex and the amygdala. These brain areas are also
      deeply involved in mediating the effects of exposure to stress on memory.
      Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA)
      transmission plays a primary role in the modulation of behavioral sequelae
      resulting from a stressful experience, and may also partially mediate inhibitory
      learning during extinction. In this review, we present evidence that exposure to
      a stressful experience may impair fear extinction and the possible involvement of
      the GABA system. Impairment of fear extinction learning is particularly important
      as it may predispose some individuals to the development of posttraumatic stress
      disorder. We further discuss a possible dysfunction in the medial prefrontal
      cortex-amygdala circuit following a stressful experience that may explain the
      impaired extinction caused by exposure to a stressor.

PMID- 17502910
TI  - Anxiety in mice: a principal component analysis study.
AB  - Two principal component analyses of anxiety were undertaken investigating two
      strains of mice (ABP/Le and C57BL/6ByJ) in two different experiments, both
      classical tests for assessing anxiety in rodents. The elevated plus-maze and
      staircase were used for the first experiment, and a free exploratory paradigm and
      light-dark discrimination were used for the second. The components in the
      analyses produced definitions of four fundamental behavior patterns: novelty
      induced anxiety, general activity, exploratory behavior, and decision making. We
      also noted that the anxious phenotype was determined by both strain and
      experimental procedure. The relationship between behavior patterns and the use of
      specific tests plus links with the genetic background are discussed.

PMID- 17502912
TI  - LTP after stress: up or down?
AB  - When an organism is exposed to a stressful situation, corticosteroid levels in
      the brain rise. This rise has consequences for behavioral performance, including
      memory formation. Over the past decades, it has become clear that a rise in
      corticosteroid level is also accompanied by a reduction in hippocampal long-term
      potentiation (LTP). Recent studies, however, indicate that stress does not lead
      to a universal suppression of LTP. Many factors, including the type of stress,
      the phase of the stress response, the area of investigation, type of LTP, and the
      life history of the organism determine in which direction LTP will be changed.

PMID- 17502911
TI  - Neurobiology of memory and anxiety: from genes to behavior.
AB  - Interaction of anxiety and memory represents an essential feature of CNS
      functioning. This paper reviews experimental data coming from neurogenetics,
      neurochemistry, and behavioral pharmacology (as well as parallel clinical
      findings) reflecting different mechanisms of memory-anxiety interplay, including
      brain neurochemistry, circuitry, pharmacology, neuroplasticity, genes, and gene
      environment interactions. It emphasizes the complexity and nonlinearity of such
      interplay, illustrated by a survey of anxiety and learning/memory phenotypes in
      various genetically modified mouse models that exhibit either synergistic or
      reciprocal effects of the mutation on anxiety levels and memory performance. The
      paper also assesses the putative role of different neurotransmitter systems and
      neuropeptides in the regulation of memory processes and anxiety, and discusses
      the role of neural plasticity in these mechanisms.

PMID- 17502913
TI  - Efficient identification of critical residues based only on protein structure by
      network analysis.
AB  - Despite the increasing number of published protein structures, and the fact that
      each protein's function relies on its three-dimensional structure, there is
      limited access to automatic programs used for the identification of critical
      residues from the protein structure, compared with those based on protein
      sequence. Here we present a new algorithm based on network analysis applied
      exclusively on protein structures to identify critical residues. Our results show
      that this method identifies critical residues for protein function with high
      reliability and improves automatic sequence-based approaches and previous network
      based approaches. The reliability of the method depends on the conformational
      diversity screened for the protein of interest. We have designed a web site to
      give access to this software at http://bis.ifc.unam.mx/jamming/. In summary, a
      new method is presented that relates critical residues for protein function with
      the most traversed residues in networks derived from protein structures. A unique
      feature of the method is the inclusion of the conformational diversity of
      proteins in the prediction, thus reproducing a basic feature of the
      structure/function relationship of proteins.

PMID- 17502914
TI  - Combinatorial computational approaches to identify tetracycline derivatives as
      flavivirus inhibitors.
AB  - Limited structural information of drug targets, cellular toxicity possessed by
      lead compounds, and large amounts of potential leads are the major issues facing
      the design-oriented approach of discovering new leads. In an attempt to tackle
      these issues, we have developed a process of virtual screening based on the
      observation that conformational rearrangements of the dengue virus envelope
      protein are essential for the mediation of viral entry into host cells via
      membrane fusion. Screening was based solely on the structural information of the
      Dengue virus envelope protein and was focused on a target site that is presumably
      important for the conformational rearrangements necessary for viral entry. To
      circumvent the issue of lead compound toxicity, we performed screening based on
      molecular docking using structural databases of medical compounds. To enhance the
      identification of hits, we further categorized and selected candidates according
      to their novel structural characteristics. Finally, the selected candidates were
      subjected to a biological validation assay to assess inhibition of Dengue virus
      propagation in mammalian host cells using a plaque formation assay. Among the 10
      compounds examined, rolitetracycline and doxycycline significantly inhibited
      plaque formation, demonstrating their inhibitory effect on dengue virus
      propagation. Both compounds were tetracycline derivatives with IC(50)s estimated
      to be 67.1 microM and 55.6 microM, respectively. Their docked conformations
      displayed common hydrophobic interactions with critical residues that affected
      membrane fusion during viral entry. These interactions will therefore position
      the tetracyclic ring moieties of both inhibitors to bind firmly to the target
      and, subsequently, disrupt conformational rearrangement and block viral entry.
      This process can be applied to other drug targets in which conformational
      rearrangement is critical to function.

PMID- 17502915
TI  - Application of broad-spectrum, sequence-based pathogen identification in an urban
      population.
AB  - A broad spectrum detection platform that provides sequence level resolution of
      target regions would have a significant impact in public health, case management,
      and means of expanding our understanding of the etiology of diseases. A
      previously developed respiratory pathogen microarray (RPM v.1) demonstrated the
      capability of this platform for this purpose. This newly developed RPM v.1 was
      used to analyze 424 well-characterized nasal wash specimens from patients
      presenting with febrile respiratory illness in the Washington, D. C. metropolitan
      region. For each specimen, the RPM v.1 results were compared against composite
      reference assay (viral and bacterial culture and, where appropriate, RT-PCR/PCR)
      results. Across this panel, the RPM assay showed >or=98% overall agreement for
      all the organisms detected compared with reference methods. Additionally, the RPM
      v.1 results provide sequence information which allowed phylogenetic
      classification of circulating influenza A viruses in approximately 250 clinical
      specimens, and allowed monitoring the genetic variation as well as antigenic
      variability prediction. Multiple pathogens (2-4) were detected in 58 specimens
      (13.7%) with notably increased abundances of respiratory colonizers (esp. S.
      pneumoniae) during viral infection. This first-ever comparison of a broad
      spectrum viral and bacterial identification technology of this type against a
      large battery of conventional "gold standard" assays confirms the utility of the
      approach for both medical surveillance and investigations of complex etiologies
      of illness caused by respiratory co-infections.

PMID- 17502916
TI  - Evolution of robustness to noise and mutation in gene expression dynamics.
AB  - Phenotype of biological systems needs to be robust against mutation in order to
      sustain themselves between generations. On the other hand, phenotype of an
      individual also needs to be robust against fluctuations of both internal and
      external origins that are encountered during growth and development. Is there a
      relationship between these two types of robustness, one during a single
      generation and the other during evolution? Could stochasticity in gene expression
      have any relevance to the evolution of these types of robustness? Robustness can
      be defined by the sharpness of the distribution of phenotype; the variance of
      phenotype distribution due to genetic variation gives a measure of 'genetic
      robustness', while that of isogenic individuals gives a measure of 'developmental
      robustness'. Through simulations of a simple stochastic gene expression network
      that undergoes mutation and selection, we show that in order for the network to
      acquire both types of robustness, the phenotypic variance induced by mutations
      must be smaller than that observed in an isogenic population. As the latter
      originates from noise in gene expression, this signifies that the genetic
      robustness evolves only when the noise strength in gene expression is larger than
      some threshold. In such a case, the two variances decrease throughout the
      evolutionary time course, indicating increase in robustness. The results reveal
      how noise that cells encounter during growth and development shapes networks'
      robustness to stochasticity in gene expression, which in turn shapes networks'
      robustness to mutation. The necessary condition for evolution of robustness, as
      well as the relationship between genetic and developmental robustness, is derived
      quantitatively through the variance of phenotypic fluctuations, which are
      directly measurable experimentally.

PMID- 17502917
TI  - Scrapie Agent (Strain 263K) can transmit disease via the oral route after
      persistence in soil over years.
AB  - The persistence of infectious biomolecules in soil constitutes a substantial
      challenge. This holds particularly true with respect to prions, the causative
      agents of transmissible spongiform encephalopathies (TSEs) such as scrapie,
      bovine spongiform encephalopathy (BSE), or chronic wasting disease (CWD). Various
      studies have indicated that prions are able to persist in soil for years without
      losing their pathogenic activity. Dissemination of prions into the environment
      can occur from several sources, e.g., infectious placenta or amniotic fluid of
      sheep. Furthermore, environmental contamination by saliva, excrements or non
      sterilized agricultural organic fertilizer is conceivable. Natural transmission
      of scrapie in the field seems to occur via the alimentary tract in the majority
      of cases, and scrapie-free sheep flocks can become infected on pastures where
      outbreaks of scrapie had been observed before. These findings point to a
      sustained contagion in the environment, and notably the soil. By using outdoor
      lysimeters, we simulated a contamination of standard soil with hamster-adapted
      263K scrapie prions, and analyzed the presence and biological activity of the
      soil-associated PrP(Sc) and infectivity by Western blotting and hamster bioassay,
      respectively. Our results showed that 263K scrapie agent can persist in soil at
      least over 29 months. Strikingly, not only the contaminated soil itself retained
      high levels of infectivity, as evidenced by oral administration to Syrian
      hamsters, but also feeding of aqueous soil extracts was able to induce disease in
      the reporter animals. We could also demonstrate that PrP(Sc) in soil, extracted
      after 21 months, provides a catalytically active seed in the protein misfolding
      cyclic amplification (PMCA) reaction. PMCA opens therefore a perspective for
      considerably improving the detectability of prions in soil samples from the
      field.

PMID- 17502918
TI  - A cyclin-dependent kinase that promotes cytokinesis through modulating
      phosphorylation of the carboxy terminal domain of the RNA Pol II Rpb1p sub-unit.
AB  - In Schizosaccharomyces pombe, the nuclear-localized kinase, Lsk1p, promotes
      cytokinesis by positively regulating the Septation Initiation Network (SIN).
      Although a member of the cyclin-dependent kinase (CDK) family, neither a cyclin
      partner nor a physiological target has been identified. In this report we
      identify a cyclin, Lsc1p, that physically interacts and co-localizes with Lsk1p.
      Furthermore, lsk1Delta, lsc1Delta, as well as kinase-dead lsk1-K306R mutants,
      display highly similar cytokinesis defects. Lsk1p is related to CDKs that
      phosphorylate the carboxy-terminal domain (CTD) of the largest sub-unit of RNA
      polymerase II (Rpb1p). Interestingly, we find that Lsk1p and Lsc1p are required
      for phosphorylation of Ser-2 residues found in the heptad repeats of the CTD. To
      determine if Rpb1p could be a physiological target, we replaced the native rpb1
      gene with a synthetic gene encoding a Rpb1p protein in which Ser-2 was
      substituted with the non-phosphorylatable amino-acid alanine in all heptads.
      Cells carrying this allele were similar to lsk1Delta mutants: They were viable,
      displayed genetic interactions with the SIN, and were unable to complete
      cytokinesis upon perturbation of the cell division machinery. We conclude that
      Ser-2 phosphorylation of the CTD heptads plays a novel physiological role in the
      regulation of cytokinesis.

PMID- 17502919
TI  - On the dynamics of the spontaneous activity in neuronal networks.
AB  - Most neuronal networks, even in the absence of external stimuli, produce
      spontaneous bursts of spikes separated by periods of reduced activity. The origin
      and functional role of these neuronal events are still unclear. The present work
      shows that the spontaneous activity of two very different networks, intact leech
      ganglia and dissociated cultures of rat hippocampal neurons, share several
      features. Indeed, in both networks: i) the inter-spike intervals distribution of
      the spontaneous firing of single neurons is either regular or periodic or
      bursting, with the fraction of bursting neurons depending on the network
      activity; ii) bursts of spontaneous spikes have the same broad distributions of
      size and duration; iii) the degree of correlated activity increases with the bin
      width, and the power spectrum of the network firing rate has a 1/f behavior at
      low frequencies, indicating the existence of long-range temporal correlations;
      iv) the activity of excitatory synaptic pathways mediated by NMDA receptors is
      necessary for the onset of the long-range correlations and for the presence of
      large bursts; v) blockage of inhibitory synaptic pathways mediated by GABA(A)
      receptors causes instead an increase in the correlation among neurons and leads
      to a burst distribution composed only of very small and very large bursts. These
      results suggest that the spontaneous electrical activity in neuronal networks
      with different architectures and functions can have very similar properties and
      common dynamics.

PMID- 17502921
TI  - HIV/AIDS Knowledge and Beliefs Among Haitian Adolescents in Miami-Dade County,
      Florida.
AB  - This study examined HIV/AIDS knowledge and beliefs in Haitian adolescents in an
      HIV epicenter, Miami-Dade Florida. This study examined survey data from 300
      Haitian adolescents, aged 13 through 18, from both low-and middle-income
      neighborhoods. A sub-sample of 80 adolescents was selected for in-depth
      interviews and continuous observations with their families and networks of
      friends, which added rich descriptions to the quantitative data. Overall
      knowledge about HIV/AIDS was high with the majority of adolescents identifying
      unprotected sex and sharing injection drug needles as HIV transmission routes.
      Moreover, approximately 75% of the adolescents reported condom use as an
      effective preventive strategy. However, misconceptions that could reduce
      adolescents' adoption of HIV preventive strategies were also identified. The
      adolescents' sources for information about HIV/AIDS as well as implications for
      prevention interventions are discussed.

PMID- 17502922
TI  - The Role of the Autism Diagnostic Observation Schedule in the Assessment of
      Autism Spectrum Disorders in School and Community Settings.
AB  - Autism diagnostic practices among school and clinical psychologists, particularly
      those using the Autism Diagnostic Observation Schedule (ADOS), were examined
      using national survey results (N = 132). School and clinical psychologists were
      similar in following the Best Practice Guidelines for screening, diagnosis and
      assessment, School psychologists were more likely to include a school or home
      observation and teacher report than clinical psychologists but evaluated
      significantly fewer children with autism spectrum disorders per year compared to
      clinical psychologists. School psychologists who were ADOS users were more likely
      to consider themselves autism experts and include a review of records than ADOS
      non-users. Perceived advantages of the ADOS included its strength in capturing
      ASD-specific behaviors and the standardized structure provided for observation,
      while diagnostic discrimination and required resources were the most commonly
      identified disadvantages.

PMID- 17502920
TI  - Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of
      Hsp72.
AB  - Heat shock proteins exert their beneficial effects via basically two modes of
      action depending on their relative location within the host. Intracellular heat
      shock proteins found within cells serve a cytoprotective role by chaperoning
      naive, misfolded and/or denatured proteins in response to stressful stimuli by a
      process known as the stress response. However, stressful stimuli also induce the
      release of intracellular heat shock proteins into the extracellular milieu and
      circulation. The extracellular heat shock protein proteins serve a
      cytostimulatory role by initiating immune responses designed to fend off
      microbial infection and destroy neoplastic transformed cells. This review will
      briefly cover recent advances into elucidating the mechanism(s) by which stress
      induces the release of heat shock proteins into the circulation, how it initiates
      immune responses and suggest the possible biological significance of circulating
      Hsp to the host.

PMID- 17502923
TI  - Expression of genes encoding mitochondrial proteins can distinguish nonalcoholic
      steatosis from steatohepatitis.
AB  - In patients without substantial alcohol use, triglyceride accumulation in the
      liver can lead to nonalcoholic fatty liver disease (NAFLD) that may progress to
      nonalcoholic steatohepatitis (NASH). The differential diagnosis between NAFLD and
      NASH can be accomplished only by morphological examination. Although the
      relationship between mitochondrial dysfunction and the progression of liver
      pathologic changes has been described, the exact mechanisms initiating primary
      liver steatosis and its progression to NASH are unknown. We selected 16 genes
      encoding mitochondrial proteins which expression was compared by quantitative RT
      PCR in liver tissue samples taken from patients with NAFLD and NASH. We found
      that 6 of the 16 examined genes were differentially expressed in NAFLD versus
      NASH patients. The expression of hepatic HK1, UCP2, ME2, and ME3 appeared to be
      higher in NASH than in NAFLD patients, whereas HMGCS2 and hnRNPK expression was
      lower in NASH patients. Although the severity of liver morphological injury in
      the spectrum of NAFLD-NASH may be defined at the molecular level, expression of
      these selected 6 genes cannot be used as a molecular marker aiding histological
      examination. Moreover, it is still unclear whether these differences in hepatic
      gene expression profiles truly reflect the progression of morphological
      abnormalities or rather indicate various metabolic and hormonal states in
      patients with different degrees of fatty liver disease.

PMID- 17502924
TI  - Role of N-acetyl-beta-d-hexosaminidase in cholesteatoma tissue.
AB  - Cholesteatoma is a destructive disease characterized by the progressive expansion
      of keratinizing squamous epithelium in the middle ear and mastoid, and chronic
      inflammatory reaction of the subepithelial connective tissue. N-Acetyl-beta-d
      hexosaminidase (HEX) catalyzes the release of terminal non-reducing N-acetyl-d
      hexosamine residues acting on glucosides and galactosides in glycoproteins, G(M2)
      gangliosides and glycosaminoglycans (GAGs). In this study the activities of HEX
      were measured in cholesteatoma tissue and in normal skin to demonstrate a
      possible role of HEX in bone resorption in the area adjacent to cholesteatoma.
      Cholesteatomas (n = 21) and normal adult retroauricular skin (controls, n = 21),
      were collected from patients during surgery due to chronic otitis media. In 20 of
      21 specimens a significantly higher activity of HEX was observed in cholesteatoma
      tissue compared with that in normal skin. Mean release of HEX from the activated
      cells was 68.55 +/- 30.77 nkat/g wet tissue in cholesteatoma and 31.79 +/- 10.02
      nkat/g wet tissue in skin specimens. It may explain the process of bone
      resorption in the area adjacent to cholesteatoma, i.e. ossicles or temporal bone.
      This study suggests that drugs inhibiting HEX activity, such as iminocyclitols,
      may be useful in cholesteatoma treatment.

PMID- 17502925
TI  - Thiamine deficiency caused by thiamine antagonists triggers upregulation of
      apoptosis inducing factor gene expression and leads to caspase 3-mediated
      apoptosis in neuronally differentiated rat PC-12 cells.
AB  - Recent evidence suggests that alterations in oxidative metabolism induced by
      thiamine deficiency lead to neuronal cell death. However, the molecular
      mechanisms underlying this process are still under extensive investigation. Here,
      we report that rat pheochromocytoma PC-12 cells differentiated in the presence of
      NGF into neurons undergo apoptosis due to thiamine deficiency caused by
      antagonists of thiamine - amprolium, pyrithiamine and oxythiamine. Confocal laser
      scanning fluorescence microscopy revealed that annexin V binds to PC-12 cells in
      presence of thiamine antagonists after 72 h incubation. Results also show that
      thiamine antagonists trigger upregulation of gene expression of mitochondrial
      derived apoptosis inducing factor, DNA fragmentation, cleavage of caspase 3 and
      translocation of active product to the nucleus. We therefore propose that
      apoptosis induced by amprolium, pyrithiamine or oxythiamine occurs via the
      mitochondria-dependent caspase 3-mediated signaling pathway. In addition, our
      data indicate that pyrithiamine and oxythiamine are more potent inducers of
      apoptosis than amprolium.

PMID- 17502926
TI  - Dynamics of estrogen-induced oxidative stress.
AB  - The objective of this study was to assess the dynamics of oxidative damage to
      cellular macromolecules such as proteins, lipids and DNA under conditions of
      oxidative stress triggering early stages of estrogen-dependent carcinogenesis. A
      rodent model of carcinogenesis was used. Syrian hamsters were sacrificed after 1,
      3, 5 h and one month from the initial implantation of estradiol. Matching control
      groups were used. Kidneys as target organs for estradiol-mediated oxidative
      stress were excised and homogenized for biochemical assays. Subcellular fractions
      were isolated. Carbonyl groups (as a marker of protein oxidation) and lipid
      hydroxyperoxides were assessed. DNA was isolated and 8-oxodGuo was assessed.
      Electron paramagnetic resonance spectroscopy was used to confirm the results for
      lipid peroxidation. Exposition to estradiol in the rodent model leads to damage
      of macromolecules of the cell, including proteins and DNA, but not lipids.
      Proteins appear to be the primary target of the damage but are closely followed
      by DNA. It has previously been speculated that protein peroxides can increase DNA
      modifications. This time sequence was observed in our study. Nevertheless, the
      direct relation between protein and DNA damage still remains unsolved.

PMID- 17502927
TI  - A novel alpha-glucosidase from the moss Scopelophila cataractae.
AB  - Scopelophila cataractae is a rare moss that grows on copper-containing soils. S.
      cataractae protonema was grown on basal MS medium containing copper. A starch
      degrading activity was detected in homogenates of the protonema, after successive
      extraction with phosphate buffer and buffer containing 3 M LiCl. Buffer-soluble
      extract (BS) and LiCl-soluble extract (LS) readily hydrolyzed amylopectin to
      liberate only glucose, which shows that alpha-glucosidase (EC 3.2.1.20) in BS and
      LS hydrolyzed amylopectin. The K(m) value of BS for maltose was 0.427. The K(m)
      value of BS for malto-oligosaccharide decreased with an increase in the molecular
      mass of the substrate. The value for maltohexaose was 0.106, which is about four
      fold lower than that for maltose. BS was divided into two fractions of alpha
      glucosidase (BS-1 and BS-2) by isoelectric focusing. The isoelectric points of
      these two enzymes were determined to be 4.36 (BS-1) and 5.25 (BS-2) by analytical
      gel electrofocusing. The two enzymes readily hydrolyzed malto-oligosaccharides.
      The two enzymes also hydrolyzed amylose, amylopectin and soluble starch at a rate
      similar to that with maltose. The two enzymes readily hydrolyzed panose to
      liberate glucose and maltose (1 : 1), and the K(m) value of BS for panose was
      similar to that for maltotriose, whereas the enzymes hydrolyzed isomaltose only
      weakly. With regard to substrate specificity, the two enzymes in BS are novel
      alpha-glucosidases. The two enzymes also hydrolyzed beta-limit dextrin, which has
      many alpha-1,6-glucosidic linkages near the non-reducing ends, more strongly than
      maltose, which shows that they do not need a debranching enzyme for starch
      digestion. The starch-degrading activity of BS was not inhibited by p
      chloromercuribenzoic acid or alpha-amylase inhibitor. When amylopectin was
      treated with BS and LS in phosphate buffer, pH 6.0, glucose, but not glucose-1
      phosphate, was detected, showing that the extracts did not contain phosphorylase
      but did contain an alpha-glucosidase. These results show that alpha-glucosidases
      should be capable of complete starch digestion by themselves in cells of S.
      cataractae.

PMID- 17502928
TI  - Gold-heterometal complexes. Evolution of a new class of luminescent materials.
AB  - A very promising area of research in which metallophilic attraction has become
      the dominating factor determining the structural patterns that give rise to
      luminescent materials is discussed. In addition to the intrinsic conditions that
      a gold complex requires to show luminescence, we show how the type and number of
      the ligands, the coordination environments around the metal centres, the
      temperature, the heterometal, the metal-metal distances, etc., increase the
      possibilities of electronic transitions and, hence, multiply the factors that
      affect the energy and number of emissions. We think that far from being a
      hindrance or a problem these findings actually give rise to a fascinating area of
      research with promising future applications, for instance, in imaging technology,
      vapour sensors, light emitting devices or even medicine, where the demand for
      optoelectronic devices is increasing every day.

PMID- 17502929
TI  - Dicarba-closo-dodecaborane(12) derivatives of phosphonium salts: easy formation
      of nido-carborane phosphonium zwitterions.
AB  - The first examples of arylphosphonium salts containing a dicarba-closo
      dodecaborane(12) (closo-carborane) are reported; in contrast to the 1,12
      carborane derivative, the 1,2- and 1,7-isomers undergo a facile deboronation
      reaction in polar solvents to afford the corresponding nido-carborane phosphonium
      zwitterions.

PMID- 17502930
TI  - Reversible structural isomerisation in rare thioether complexes of cobalt(II)-
      effects of ligand architecture.
AB  - Rare examples of (high spin) Co(II) complexes with geometrically constrained
      tetrathioether ligands exhibit a very unusual structural isomerism, switching
      reversibly between tetrahedral monomers in solution and octahedral chain polymers
      in the solid; the crystal structures of one polymeric species and a tetrahedral
      monomer model compound are described.

PMID- 17502931
TI  - A ketone oximate based cyclic cationic [Ni(II)4] inverse metallacrown from
      simultaneous chelation and bridging of two ligands.
AB  - The Ni(4) inverse metallacrown (NHEt(3)) [Ni(4)(bmo)4(Hael)2(ael)2](ClO(4))3
      [(NHEt(3)).1.(ClO(4))3], with the inverse 12-MC-4 motif, has been assembled via
      simultaneous chelation and bridging of butan-2,3-dionemonoxime (Hbmo) and 2-amino
      ethanol (Hael).

PMID- 17502932
TI  - Efficient nickel mediated carbon-carbon bond cleavage of organonitriles.
AB  - The reactions of the nickel complex [Ni(2)(iPr(2)Im)4(COD)] 1 with organonitriles
      smoothly and irreversibly proceed via intermediates with eta(2)-coordinated
      organonitrile ligands such as [Ni(iPr(2)Im)2(eta(2)-(CN)-PhCN)] 2 and
      [Ni(iPr(2)Im)2(eta(2)-(CN)-pTolCN)] 4 to yield aryl cyanide complexes of the type
      trans-[Ni(iPr(2)Im)2(CN)(Ar)] (Ar = Ph 3, pTol 5, 4-CF(3)C(6)H(4) 6, 2,4
      (OMe)2C(6)H(3) 7, 2-C(4)H(3)O 8, 2-C(5)H(4)N 9). The compounds 3, 7, 9 and have
      been structurally characterized. For the conversion of 2 to 3 a free activation
      enthalpy DeltaG++(328 K) of 103.47 +/- 0.79 kJ mol(-1) was calculated from time
      dependent NMR spectroscopy. The analogous reaction of arylnitriles with electron
      releasing substituents or heteroaromatic organonitriles is significantly faster
      compared to the reaction with benzonitrile or toluonitrile. The reactions of 1
      with acetonitrile or trimethylsilyl cyanide afforded [Ni(iPr(2)Im)2(CN)(Me)] 10
      and structurally characterized [Ni(iPr(2)Im)2(CN)(SiMe(3))] 11. The usage of an
      organonitrile with a longer alkyl chain, adiponitrile, yielded
      [Ni(iPr(2)Im)2(eta(2)-(CN)-NCC(4)H(8)CN)] 12 as well as the C-CN activation
      product [Ni(iPr(2)Im)2(CN)(C(4)H(8)CN)]13 in thermal and photochemical reactions,
      although this pathway seems to be significantly interfered with by decomposition
      pathways under the formation of the dicyanide complex [Ni(iPr(2)Im)(2)(CN)(2)]
      14.

PMID- 17502933
TI  - Pyrazolate-based copper(II) and nickel(II) [2 x 2] grid complexes: protonation
      dependent self-assembly, structures and properties.
AB  - The pyrazole-based diamide ligand N,N'-bis(2-pyridylmethyl)pyrazole-3,5
      dicarboxamide (H(3)L) has been structurally characterised and successfully
      employed in the preparation of [2 x 2] grid-type complexes. Thus, the reaction of
      H(3)L with Cu(ClO(4))2.6H(2)O or Ni(ClO(4))2.6H(2)O in the presence of added base
      (NaOH) affords the tetranuclear complexes [M(4)(HL(4))].8H(2)O (1: M = Cu, 2: M =
      Ni). Employment of a mixture of the two metal salts under otherwise identical
      reaction conditions leads to the formation of the mixed-metal species [Cu(x)Ni(4
      x)(HL)(4)].8H(2)O (x<or= 4; for x = 2: 3). Complexes 1-3 have been structurally
      characterised and found to be isomorphous, with each ligand strand acting as a
      hybrid N3-NO chelator. The copper ions in 1 are in a distorted square-pyramidal
      N(4)O coordination environment with rather long M-O(apical) distances. The
      coordination sphere about the nickel ions in 2 is roughly the same, but with even
      longer M...O distances, and it is therefore best described as N4 square-planar
      with low-spin nickel(II) ions. The single crystal X-ray data obtained for the
      mixed-metal complex 3 gave the best results assuming a statistical distribution
      of copper and nickel ions. X-Band EPR spectra of 1 and 2 indicate magnetically
      coupled copper(II) ions and low-spin nickel(II), respectively. EPR spectra of a
      powdered sample of a complex with the general formulation [Cu(x)Ni(4
      x)(HL)4].8H(2)O with a large excess of Ni(2+) (95%) was shown to be
      characteristic for individual copper(II) ions in the tetranuclear grid system.
      Magnetic susceptibility data of 1 indicate weak antiferromagnetic spin coupling
      between the copper ions (J = -8.2 +/- 0.4 cm(-1)), which is explained by the
      particular spatial arrangement of the magnetic orbitals.

PMID- 17502934
TI  - A new high pressure phase of sodium formate dihydrate; an experimental and
      computational study.
AB  - As part of an on-going programme to study the high pressure structural behaviour
      of hydrated small molecular systems, sodium formate dihydrate has been studied
      using high pressure single crystal X-ray and neutron powder diffraction methods.
      A new phase was initially identified at 17 kbar by X-ray diffraction and high
      level quantum mechanical calculations completed the structure, allowing
      definitive hydrogen atom positioning. The resulting structure compared favourably
      with that found subsequently by high pressure neutron diffraction. The neutron
      diffraction study also revealed that the deuterated form, NaDCO(2).2D(2)O, is
      stable in a different structural form to that of the non-deuterated material at
      ambient pressure. The structure of this phase is related to that of the high
      pressure phase via a simple translation of the molecular layers.

PMID- 17502935
TI  - Intercalation of fac-[(4,4'-bpy)ReI(CO)3(dppz)]+, dppz = dipyridyl[3,2-a:2'3'
      c]phenazine, in polynucleotides. On the UV-vis photophysics of the Re(I)
      intercalator and the redox reactions with pulse radiolysis-generated radicals.
AB  - The intercalation of fac-[(4,4'-bpy)Re(I)(CO)3(dppz)]+ (dppz = dipyridyl[3,2
      a:2'3'-c]phenazine) in polynucleotides, poly[dAdT]2 and poly[dGdC]2, where A =
      adenine, G = guanine, C = cytosine and T = thymine, is a major cause of changes
      in the absorption and emission spectra of the complex. A strong complex
      poly[dAdT]2 interaction drives the intercalation process, which has a binding
      constant, Kb approximately 1.8 x 10(5) M(-1). Pulse radiolysis was used for a
      study of the redox reactions of e(-)(aq), C*H(2)OH and N3* radicals with the
      intercalated complex. These radicals exhibited more affinity for the intercalated
      complex than for the bases. Ligand-radical complexes, fac-[(4,4'
      bpy*)Re(I)(CO)3(dppz)] and fac-[(4,4'-bpy)Re(I)(CO)3(dppz *)], were produced by
      e(-)(aq) and C*H(2)OH, respectively. A Re(II) species, fac-[(4,4'
      bpy)Re(II)(CO)3(dppz)](2+), was produced by N3* radicals. The rate of
      annihilation of the ligand-radical species was second order on the concentration
      of ligand-radical while the disappearance of the Re(II) complex induced the
      oxidative cleavage of the polynucleotide strand.

PMID- 17502936
TI  - A comparative study of the structures and reactivity of cyclometallated platinum
      compounds of N-benzylidenebenzylamines and cycloplatination of a primary amine.
AB  - The reaction of cis-[PtCl(2)(dmso)2] with ligands 4-ClC(6)H(4)CHNCH(2)C(6)H(5)
      (1a) and 4-ClC(6)H(4)CHNCH(2)(4-ClC(6)H(4)) (1b) in the presence of sodium
      acetate and using either methanol or toluene as solvent produced the
      corresponding five-membered endo-metallacycles [PtCl{(4
      ClC(6)H(3))CHNCH(2)C(6)H(5)}{SOMe(2)}] (2a) and [PtCl{(4-ClC(6)H(3))CHNCH(2)(4'
      ClC(6)H(4))}{SOMe(2)}] (2b). An analogous reaction for ligands 2,6
      Cl(2)C(6)H(3)CHNCH(2)C(6)H(5) (1c) and 2,6-Cl(2)C(6)H(3)CHNCH(2)(4-ClC(6)H(4))
      (1d) produced five-membered exo-metallacycles [PtCl{(2,6
      Cl(2)C(6)H(3))CHNCH(2)C(6)H(4)}{SOMe(2)}] (2c) and [PtCl{(2,6
      Cl(2)C(6)H(3))CHNCH(2)(4'-ClC(6)H(3))}{SOMe(2)}] (2d) when the reaction was
      carried out in methanol and seven-membered endo-platinacycles
      [PtCl{(MeC(6)H(3))ClC(6)H(3)CHNCH(2)C(6)H(4)}{SOMe(2)}] (3c) and
      [PtCl{(MeC(6)H(3))ClC(6)H(3)CHNCH(2)(4'-ClC(6)H(3))}{SOMe(2)}] (3d) when toluene
      was used as a solvent. The reaction of 2,4,6-(CH(3))(3)C(6)H(2)CHNCH(2)(4
      ClC(6)H(4)) (1e) produced in both solvents an exo-platinacycle [PtCl{(2,4,6
      (CH(3))(3)C(6)H(2))CHNCH(2)(4'-ClC(6)H(3))}{SO(CH(3))(2)}] (2e). Cyclometallation
      of 4-chlorobenzylamine was also achieved to produce compound [PtCl{(4
      ClC(6)H(3))CH(2)NH(2)}{SOMe(2)}] (2g). The reactions of endo- and exo
      metallacycles with phosphines evidenced the higher lability of the Pt-N bond in
      exo-metallacycles while a comparative analysis of the crystal structures points
      out a certain degree of aromaticity in the endo-metallacycle.

PMID- 17502937
TI  - Stereogenic properties of spiranes combined with four equivalent conventional
      centres of chirality.
AB  - Derivatives of the tri-spirane pentaerythritoxy-cyclophosphazene compound, 1,
      have been used to investigate the stereogenic properties of spiranes combined
      with four equivalent conventional centres of chirality. In compound 1 the two
      inner rings are carbocyclic and symmetrical and the two outer rings are
      cyclotriphosphazenes substituted in different positions to provide the
      conventional centres of chirality. The case of combining spiranes with four
      equivalent centres of chirality has been investigated by the reaction of 1 with
      dimethylamine in a 1 : 8 molar ratio to give four diastereoisomeric products, in
      which the two cyclophosphazene rings are non-geminally di-substituted in either
      cis or trans configurations; viz. the cis-cis (2a), cis-trans (2b) and two trans
      trans substituted dimethylamine derivatives 2c and 2d. The structure and
      stereogenic properties of compound 2a (C2 symmetry) have been characterized
      previously by both X-ray crystallography and 31P NMR spectroscopy on addition of
      a chiral solvating agent (CSA) and the structures and stereogenic properties of
      compounds 2b (C1) and 2d (C2) have been similarly characterized in this work. The
      structure of compound 2c has been characterised by X-ray crystallography and
      found to be meso with the relatively rare S4 symmetry. The four diastereoisomeric
      products 2a-2d represent all the possible stereochemical isomers of a spirane
      combined with four equivalent conventional centres of chirality.

PMID- 17502938
TI  - The synthesis and properties of iridium(III)-cored dendrimers with carbazole
      peripherally functionalized beta-diketonato dendrons.
AB  - A simple convergent synthetic approach has been developed for the synthesis of
      iridium(III)-cored dendrimers with carbazole peripherally functionalized beta
      diketonato dendrons. The zeroth- to third-generation green-emitting dendrimers
      were synthesized by reacting the corresponding beta-diketonato dendrons with
      iridium(III) dimer under mild conditions with good yields, respectively. This
      approach proved to be modular, and could be used to prepare blue-green-emitting
      and red-emitting dendrimers with the same beta-diketonato dendrons only by using
      different cyclometallating ligands. The resulting dendritic ligands and
      iridium(III)-cored dendrimers were well characterized. Their photoluminescent
      properties both in solution and in the solid state were tested. It was found that
      all the dendrimers retained the photophysical properties of the corresponding
      small analogues with high emission quantum yields (0.06-0.30). Preliminary
      results indicated that these dendrimers functionalized carbazole units exhibited
      distinct light-harvesting potential, resulting in a strong intense emission from
      the iridium core of the dendrimers.

PMID- 17502939
TI  - Low temperature crystal structures of apatite oxygen-conductors containing
      interstitial oxygen.
AB  - Oxygen-stoichiometric La(9.33) square(0.67)(Si(6)O(24))O2 and oxygen-excess
      La(8.65)Sr(1.35)(Ge(6)O(24))O(2.32) and La(8.65)Sr(1.35)(Si(6)O(24))O(2.32) oxy
      apatites have been structurally characterized at low temperatures by the Rietveld
      method. Oxygen-interstitial distribution has been studied at 15 K for La(9.33)
      square(0.67)(Si(6)O(24))O2 and La(8.65)Sr(1.35)(Ge(6)O(24))O(2.32) by time-of
      flight neutron powder diffraction and at 4 K for
      La(8.65)Sr(1.35)(Si(6)O(24))O(2.32) by constant-wavelength neutron powder
      diffraction. The low temperature structural study was undertaken in order to
      distinguish between the effects of static disorder, originated mainly from the
      presence of interstitial oxygens, and the anisotropic thermal vibrations. At such
      low temperatures, the influence of the anisotropic thermal vibrations is
      minimised. This structural study has firmly established the existence of
      interstitial oxygens in these materials, which may be useful as electrolytes for
      solid oxide fuel cells.

PMID- 17502940
TI  - Synthesis, structural studies and reactivity of vanadium complexes with
      tridentate (OSO) ligand.
AB  - The direct reaction between [VCl(3)(thf)3] or [VO(OEt)3] and 2,2'-thiobis{4
      (1,1,3,3-tetramethyl-butyl)phenol (tbopH(2)) leads to the formation of
      [V(2)(micro-tbop-kappa(3)O,S,O)2Cl(2)(CH(3)CN)(2)] (1).4CH(3)CN or [V(2)(micro
      OEt)2(O)2(tbop-kappa(3)O,S,O)2] (2), respectively, in high yield. Compounds 1 and
      2 were characterized by chemical and physical techniques including X-ray
      crystallography and variable temperature magnetic susceptibility studies (J = 
      29.1 cm(-1)) for 1. Complexes 1 and 2 were supported on MgCl2 and when activated
      with aluminium alkyls, were found to effectively polymerize ethene to produce
      polyethylene with a narrow molecular weight distribution M(w)/M(n) approximately
      3.

PMID- 17502941
TI  - Two WV-MnIII bimetallic assemblies built by octacyanotungstate(v) and MnIII
      Schiff bases: molecular structures and a spin-flop transition.
AB  - Two W(V)-Mn(III) bimetallic compounds, [Mn(Cl-salmen)(H(2)O)2]{[Mn(5
      Clsalmen)(H(2)O)]2[W(CN)8].2H(2)O (1.2H(2)O) [5-Clsalmen = N,N'-(1
      methylethylene)bis(5-chlorosalicylideneiminato) dianion], which contains
      trinuclear Mn(2)W and isolated Mn(III) moieties, and [Mn(3
      MeOsalcy)(H(2)O)2]3[W(CN)(8)].2H(2)O (2.2H(2)O) [3-MeOsalcy = N,N'-(trans-1,2
      cyclohexanediylethylene)bis(3-methoxysalicylideneiminato) dianion] molecules were
      prepared in redox processes and characterized using X-ray analysis and magnetic
      measurements. Compound 1 is composed of the {[Mn(5-Clsalmen)(H(2)O)]2[W(CN)8]}-
      trimer, in which two CN groups among eight in [W(CN)8](3-) bridge W(5+) and two
      Mn(3+) ions and the remaining CN ligands are hydrogen-bonded to water molecules
      or unbound, and the [Mn(Cl-salmen)(H(2)O)2]+ cation. Subsequently, two water
      molecules of the isolated cation are subject to hydrogen bonds. For 2, there are
      no covalent bonds among the subunits and six serial stacks of [Mn(3
      MeOsalcy)(H(2)O)2]+ units are all hydrogen-bonded. The many hydrogen bonds found
      in both complexes eventually lead to three-dimensional networks. The magnetic
      studies for 1 reveal that antiferromagnetic interactions (J = -5.4 cm(-1))
      between W(V) and Mn(III) centers within the trimer are transmitted via the
      bridging CN groups. Intermolecular antiferromagnetic couplings (zJ' = -0.2 cm(
      1)) are also observed. The static and dynamic magnetic data of 1 demonstrate the
      existence of a field-induced spin-flop transition occurring among the clusters
      and monomeric molecules.

PMID- 17502942
TI  - Kinetics and mechanism of the reaction of Cr(II) aqua ions with benzoylpyridine N
      oxide.
AB  - Aqueous chromium(II) ions, Cr(aq)(2+), react with benzoylpyridine oxide (BPO)
      much more rapidly than with other pyridine N-oxides previously explored. The
      kinetics were studied under pseudo-first order conditions with either reagent in
      excess. Under both sets of conditions, the major kinetic term exhibits first
      order dependence on limiting reagent, and second order dependence on excess
      reagent, i.e.k(Cr) = k2(Cr)[BPO][Cr(aq)(2+)]2 (excess Cr(aq)(2+)), and k(BPO) =
      k2(BPO)[Cr(aq)(2+)][BPO](2) (excess BPO), where k2(Cr) = (6.90 +/- 0.27) x 10(4)
      M(-2) s(-1) and k2(BPO) = (3.32 +/- 0.28) x 10(5) M(-2) s(-1) in 0.10 M HClO4.
      The rate constant k2(Cr) contains terms corresponding to [H+]-independent and
      [H+]-catalyzed paths. In the proposed mechanism, the initially formed
      Cr(aq)(BPO)(2+) engages in parallel oxidation of Cr(aq)(2+) and reduction of BPO.
      The latter reaction provides the basis for a convenient new preparative route for
      the BPO complex of Cr(III).

PMID- 17502943
TI  - Direct solvothermal growth, crystal structures, and optical properties of one
      dimensional lanthanide selenidoarsenate(v) polymers [Ln(dien)2(micro3-AsSe4)] (Ln
      = Nd, Sm): the first example of an AsSe4(3-) anion acting as a ligand to a
      lanthanide complex.
AB  - Two novel lanthanide selenidoarsenates(v) [Ln(dien)2(micro(3)-AsSe(4))] (Ln = Nd
      1, Sm 2, dien = diethylenetriamine) were synthesized by the reactions of
      As(2)O(3) and Se with Nd(2)O(3) or Sm(2)O(3) in dien under solvothermal
      conditions. 1 and 2 are in the orthorhombic crystal system with Iba2 and Pbca
      space groups, respectively. The [AsSe(4)](3-) anion acts as a tridentate micro(3)
      AsSe(4) ligand to bridge the lanthanide [Ln(dien)2](3+) complexes leading to one
      dimensional neutral [Ln(dien)(2)(micro(3)-AsSe(4))](infinity) chains. The chains
      contact through hydrogen bonding to form network structures. The lanthanide
      center lies within a nine-coordinated environment involving six N atoms of two
      dien ligands and three Se atoms of two different tetrahedral [AsSe(4)](3-) anions
      forming a distorted monocapped square antiprism. The novel coordination polymers
      [Nd(dien)2(micro(3)-AsSe(4))](infinity) and [Sm(dien)2(micro(3)
      AsSe(4))](infinity) are the first examples of solvothermally synthesized
      selenidoarsenates with [AsSe(4)](3-) anion acting as a ligand in lanthanide
      complexes. The band gaps of 2.11 eV for 1, and 2.18 eV for 2 have been derived
      from optical absorption spectra. TG-DSC curves show that two compounds remove
      coordinated dien ligands in a single step.

PMID- 17502944
TI  - Blue nevi of internal organs are more similar to the so-called dermal
      melanocytosis than to cutaneous blue nevi.
AB  - In this report, we examine several morphologic aspects of blue nevi of internal
      organs, and compare them to similar conditions of the skin. From a morphologic
      point of view, blue nevi of internal organs are more similar to the so-called
      dermal melanocytoses. Nevertheless, since melanocytoses and blue-nevi seem to
      have the same benign prognosis, and since blue nevus is a historically
      consolidated term to refer to pigmented spindle cell lesions of internal organs,
      a most appropriate term, to refer to the latter, will not be easily accepted in
      literature.

PMID- 17502945
TI  - Increased mast cell density and microvessel density in the thymus of patients
      with myasthenia gravis.
AB  - There were investigated 15 cases with normal thymus removed during cardiac
      surgery and nine cases with clinical signs of myasthenia gravis. Four patients
      with myasthenia gravis had thymoma (three invasive, one non-invasive). Specimens
      were fixed in buffer formalin, embedded in paraffin and slides were stained with
      Hematoxylin-Eosin and Alcian blue-Safranin. Additional slides were stained for
      factor VIII in order to estimate microvessel density. Mast cell density was
      performed at magnification x400, and microvessel density at magnification x200,
      using the "hot spot" method. There were found intralobular mast cells in all
      cases, located mainly in the cortex (6.53 in the normal thymus, 21.4 in patients
      with myasthenia gravis, and 10 in thymoma-associated myasthenia gravis). A
      significant increase in the number of intralobular mast cells was noticed in
      patients with myasthenia gravis without thymoma (p < 0.001), and a moderate
      increase in patients with thymoma-associated myasthenia gravis (p < 0.023).
      Values of microvessel density were 10.3 for the normal thymus, 33 for myasthenia
      gravis without thymoma and 21.8 for myasthenia gravis with associated thymoma. A
      strong correlation was found between the number of mast cells and microvessel
      densities in all three conditions.

PMID- 17502946
TI  - Modified variant of the Rieske iron-sulfur protein in the hippocampus of kindled
      rats and human epileptic patients.
AB  - Kindled seizures are widely used to model epileptogenesis, but the molecular
      mechanisms underlying the attainment of kindling status are largely unknown.
      Recently we showed that achievement of kindling status in the Sprague-Dawley rat
      is associated with a critical developmental interval of 25 +/- 1 days; the
      identification of this long, well-defined developmental interval for inducing
      kindling status makes possible a dissection of the cellular and genetic events
      underlying this phenomenon and its relationship to normal and pathological brain
      function. Now we report the identification, by proteomics, of a modified variant
      of the Rieske iron-sulfur protein, a component of the mitochondrial cytochrome
      bc1 complex, whose isoelectric point is shifted toward more alkaline values in
      the hippocampus of kindled rats. By immunohistochemistry the Rieske protein is
      well-expressed in the hippocampus except in the CA1 subfield, a region of
      selective vulnerability to seizures in humans and animal models. We also noted an
      asymmetric, selective expression of the Rieske protein in the subgranular neurons
      of the dorsal dentate gyrus, a region implicated in neurogenesis. Abnormal
      changes in Rieske protein immunoreactivity also were found in sections obtained
      from human epileptic patients. These results suggest that the Rieske protein may
      play a role in the response of neurons to seizure activity and could give
      important new insights into the molecular pathogenesis of epilepsy.

PMID- 17502947
TI  - Angiogenesis and ER/PR status in primary breast cancer patients: an analysis of
      158 needle core biopsies.
AB  - Formation of new blood vessels from a preexisting vascular bed (angiogenesis) is
      a complex multistep process, which may also permit metastasis. Estrogen and
      progesterone are important in breast tumorigenesis, and their effects on the
      breast are mediated by their respective receptors, the estrogen receptor (ER) and
      the progesterone receptor (PR). To investigate how tumor angiogenesis correlates
      with ER/PR status in breast carcinoma diagnosed on core biopsy, microvessels were
      counted (and graded the density of microvessels) within the initial invasive
      carcinomas of 158 patients. Using light microscopy, the number of microvessels
      was counted manually in a subjectively selected hot spot (in the most active
      areas of neovascularization per 400x field), and their values were separated as
      above or below median (low and high), without knowledge of the outcome in the
      patient or any other pertinent variable. When the mean values of MVD of the
      various groups defined by ER/PR status were compared, significant difference was
      noted (P = 1.57E-05). When tumors were classified as high or low MVD, based on a
      cut-off value (30.70175 microvessels/mm(2)), cases with high MVD were
      significantly more numerous in patients with ER+/PR- status. MVD did show a
      relationship with groups defined by ER/PR status (P = 0.000801). Assessment of
      tumor angiogenesis may therefore prove valuable in selecting patients with early
      breast carcinoma for therapeutic hormonal therapy.

PMID- 17502948
TI  - The histological changes of digestive organs in experimental decreases of hepatic
      venous outflow at the rat.
AB  - The hepatic venous outflow may be diminishing in right-sided heart diseases,
      constrictive pericarditis, obstruction of suprahepatic veins or an inferior vena
      cave. It was created an experimental model by obstruction of the suprahepatic
      veins lumen and inferior vena cave, too, at the adult Wistar rats. The animals
      were sacrificed in the 30 days after operation. At the iterative laparatomy it
      was found the liver more increased in volume, a little amount of ascites in
      peritoneal cavity, oedema of the digestive organs walls. Liver and stomach
      fragments were prelevated and were processed for optic microscopy and electronic
      microscopy. The morphological study using by usual technics has highlighted
      vascular stasis in gastric submucosa. In liver it is standed out the
      pericentrolobular vascular stasis, inflammatory lymphoplasmocytic infiltrate
      around the end of hepatic vein. In the gastric submucosa have found vascular
      stasis, and within the chorion mucosa, the high capillary hyperemia. There is a
      discreet vacuolar feature on epithelium surface of the gastric mucosal in pyloric
      region. In the other layers, at rats the epithelium multistratum keratinizated of
      the stomach is without changes, in this region is maintaining the hyperemia in
      mucosal chorion.

PMID- 17502949
TI  - CD105/smooth muscle actin double immunostaining discriminate between immature and
      mature tumor blood vessels.
AB  - The aim of the study was to demonstrate the value of the double immunostaining
      for endothelial and perivascular cell to discriminate mature from immature tumor
      associated blood vessels in mammary carcinoma. We used the specific endothelial
      marker CD105 to highlight the activated endothelial cells and antibodies against
      smooth muscle cell actin (SMA) for perivascular cells, applying Envision
      Doublestain system (HRP/DAB-APAAP/Fast Red). We found an inverse correlation
      between the immunoexpression of CD105 and SMA in normal vessels and a strong
      positive signal for CD105 in the intratumor single endothelial cells and immature
      vessels. Only few blood vessels were positive for both CD105 and SMA within the
      tumor area. The signal for the endothelial marker was weak and inconstant, and
      significantly diminished when the SMA immunoexpression was increased for the same
      vessel. The differentiation between vessels with and without perivascular cells
      coverage using double immunostaining for CD105/SMA may be an important step in
      the selection of the mammary tumors, which could have a high grade of
      responsiveness to antiangiogenic therapy with monoclonal antibodies against CD105
      antigen.

PMID- 17502950
TI  - Ultrastructural features of blood cells in atherosclerosis.
AB  - Atherosclerosis is a complex process that affects specific tissues of the
      vasculature, susceptible to developing atherosclerosis. >From 10 patients with
      atherosclerosis, between 50-70 years, peripheral blood was prelevated and after
      the technical procedures the blood cells were studied using the electron
      microscopy. The most characteristic morphological modifications were observed in
      agranulocytes and platelets. The granulocytes polymorphs showed insignificant
      ultrastructural changes, and the erythrocytes presented weak anizocytosis and
      poikilocytosis.

PMID- 17502951
TI  - Antiviral therapy effects upon hepatitis C cholestatic syndrome.
AB  - Cholestasis includes, as a syndrome, all clinical and biological manifestations
      caused by the deficient or simply absent biliar secretion or caused by the
      obstruction of the biliary ducts. The hepatic cholestasis from the chronic
      hepatitis C (HC VHC) is a result of the altered interlobular biliary canalicules,
      caused by the modified cellular transport mechanisms and it is associated with a
      medium to severe degree of fibrosis. The aim of this study was to evaluate the
      efficiency of antiviral therapy in HC VHC patients. The study included a number
      of 37 HC VHC patients admitted at the Medical Department no. 1 of the Emergency
      County Hospital of Craiova; they were treated with Pegasys, 180 microg/week and
      Copegus, 1000 or 1200 mg/day, taking in consideration their weight, for 48 weeks
      and they were monitored for 24 weeks after the treatment. The following
      parameters were analyzed: direct bilirubine, total cholesterol, alkaline
      phosphatase, gamma-glutamiltranspeptidase and leucin-aminopeptidase. Under
      treatment, the clinical status caused by the cholestasis (pruritus, icteric
      syndrome, hemoragipary syndrome) was improved in six of the given cases (16.22%).
      Before therapy, the hepatic cholestasis was present in 20 patients (54.05%), and
      after treatment in 14 patients (37.83%). During therapy, the average values for
      all the monitored parameters decreased: direct bilirubine (0.38 +/- 0.18 mg/dl
      vs. 0.34 +/- 0.24 mg/dl, p = 0.0867), total cholesterol (198.53 md/dl vs. 183.16
      mg/dl, p = 0.0808), alkaline phosphatase (236.99 +/- 79.09 iu/l vs. 227.82 +/-
      87.59 iu/l, p = 0.0845), gamma-glutamiltranspeptidase (47 +/- 32.89 iu/l vs.
      43.91 +/- 29.66 iu/l, p = 0.1509), and leucin-aminopeptidase (32.33 +/- 13.22
      iu/l vs. 28.95 +/- 14.22 iu/l, p = 0.0038). Under antiviral treatment there was
      noticed an improvement of the cholestasis clinical status in a small number of
      cases. Antiviral therapy favorably influenced the liver cholestasis associated in
      patients with chronic hepatitis C in a rather small proportion. Under Interferon
      pegylate and Ribavirine treatment, low levels of direct bilirubine, cholesterol
      and enzymes were found. Hepatic cholestasis and, especially, the high serum
      values of gamma-glutamiltranspeptidase have a negative influence upon antiviral
      therapy, causing the low sustained virological response.

PMID- 17502952
TI  - Study of the celiac ganglia development.
AB  - The celiac ganglia and the visceral plexus are complexes structures, disposed in
      the proximity of the main collateral branches of the aorta. Pre visceral ganglia
      are sympathetic ganglia chains between the lateral vertebral sympathetic chain
      and viscera. Our study is made in the anatomy lab on 30 adult human bodies, one
      of new born and 10 human fetal specimens with crown-rump lengths from 9 to 28 cm.
      It was used the argental impregnation by Bielschowsky on block and Trichrome
      Masson methods for microscopic evidence. Prenatal, celiac ganglia are not a good
      defined morphological unit. They show a delay of neuroblastic maturation,
      comparing with the par vertebral ganglia. The nervous functional unit is
      represented by the neuron. The ontogenesis of the celiac ganglia follows several
      stages. Then, the neuronal specialization and the functional neuronal maturation
      are processes based on the numeric and morphological remodeling of the neuronal
      connecting figure, pre ganglia and post ganglia.

PMID- 17502953
TI  - Morphological changes positive correlates with oxidative stress in COPD.
      Preliminary data of an experimental rat model--study and literature review.
AB  - It is well known that nicotine that is a major toxic component of cigarette smoke
      induces oxidative stress which is responsible for the lung damages in COPD and
      cancer. There have been reported some cases of COPD in never smoking patients
      exposed to air pollutants. The aim of our study is to evaluate the morphological
      pulmonary changes in rats exposed to cigarette smoke respectively to solid
      combustible smoke and to establish the relationship between the exposure and the
      level of oxidative stress measured through serum (s) and pulmonary tissue (l) MDA
      in rats (TBARS method). Thirty Wistar rats were divided into three groups (n =
      10): (1) the control group (C), (2) the cigarette smoke group (CS), and (3) the
      solid combustible smoke group (SC). Apart from the control group, these were
      treated with solid combustibles smoke or cigarette smoke for six months. We
      collected blood for serum determination of MDA and the lungs were removed for
      histopathological analysis and to determine the levels of malondialdehyde (MDA).
      The levels of serum and lung MDA were significantly higher in CS and SC groups
      compared with C group, but not significantly differences between CS and SC group
      were detected. These findings are positively correlated with histopathological
      changes (squamous metaplasia and clear cell hyperplasia in the bronchium
      epithelium, emphysema) found in pulmonary tissue. Preliminary data of our study
      confirms that not only the cigarette smoke but also the environmental pollutants
      are involved in the major pathways of COPD.

PMID- 17502954
TI  - Holt-Oram syndrome.
AB  - The Holt-Oram syndrome or atriodigital dysplasia is an autosomal dominant
      disorder with near complete penetrance and variable expression, caused by
      mutations of the TBX5 gene (12q24.1), affecting one in 100 000 live births. 60%
      of cases are familial and 40% sporadic. We present the case of a 24 years old
      male patient with a personal history of bilateral coxa vara surgically corrected
      on the right at the age of 8 years, complicated by osteochondritis, short stature
      (160 cm), underweight (37 kg, BMI 14.45 kg/cm(2)), triangular face, micrognathia,
      down slanting palpebral fissures, hypertelorism, low set ears, scoliosis, narrow
      shoulders, shortened left arm, left thumb agenesia, limited supination, abnormal
      toes, hypoplastic muscles, atrial septal defect ostium secundum type, incomplete
      right bundle branch block, hypoacusia and normal intelligence.

PMID- 17502955
TI  - Anomalous channels draining the internal iliac veins: embryological and clinical
      significance.
AB  - During a routine cadaver dissection, we have encountered an anomalous formation
      of inferior vena cava and abnormal channels communicating the two internal iliac
      veins with the inferior vena cava in a 67 year old male cadaver. The said
      channels which had a caliber of 5 mm on the left side and 15 mm on the right
      arose at a distance of 26 mm on the left and 35 mm on the right from the internal
      iliac vein termination. Both the said channels moved medially and joined one
      another and formed a common stem (Cs) which finally terminated at the junction of
      the termination of right iliac vein into the inferior vena cava. The lumen of the
      terminal part had a diameter of 18 mm and it was 20 mm in length. Anomalies of
      the inferior vena cava and renal veins occur infrequently but if unidentified can
      lead to significant morbidity during surgical exploration. An understanding of
      the embryologic development of the vena cava and its tributaries is necessary to
      understand the genesis of these sometimes complex anomalies and their
      accompanying anatomic variants.

PMID- 17502956
TI  - Collision adenocarcinoma--carcinoid tumor of the colon. Case report and review of
      the literature.
AB  - Collision tumors are extremely rare and raise interesting problems related to
      histogenesis. In this paper we report a case of collision tumor of the colon and
      review the literature related to this subject.

PMID- 17502957
TI  - Adenosarcoma of the uterine cervix: positive and differential diagnosis.
AB  - Adenosarcoma is considered as being a variety of mixed Mullerian tumor having a
      small grade of malignity. Present case refers to a perimenopause patient examined
      for a structure of bleeding endocervical polypoid. Diagnostic evaluation
      performed after biopsy revealed a cervical leiomyosarcoma followed by operation.
      The range of occurrence is interesting, having in mind positive and differential
      diagnosis problems that occurred.

PMID- 17502958
TI  - Mesenteric inflammatory veno-occlusive disease as a rare cause of acute abdomen.
AB  - Mesenteric inflammatory veno-occlusive disease is a rare but recognized cause of
      intestinal ischemia, who can be defined as phlebitis or venulitis affecting
      mesentery or the bowel, without any evidence of coexisting of an obvious
      predisposing cause or a coexisting arterial inflammatory involvement. We report
      the case of a male patient, 63 year old, admitted in the Emergency County
      Hospital of Craiova, who after presenting with an acute abdomen, underwent
      exploratory laparotomy and resection of the ischemic sigmoid, temporary colostomy
      and after four months we reintroduced descendent colon in the digestive transit.
      The resected specimen of the patient was examined histopathologically, and
      distinctive histopathological characteristics of the mesenteric inflammatory veno
      occlusive disease were identified.

PMID- 17502959
TI  - [Birth-weight curves].
AB  - OBJECTIVE: This work was aimed at constructing curves relating birth-weight to
      gestational age; these can be used as a standard for the newborn in Colombia.
      METHOD: The curves were drawn up using birth-weights from pregnancies lasting 22
      44 weeks. Three tables were drawn up; these are presented, along with their
      respective graphs. They were constructed using monotonic regression from the
      sample percentiles computed in strata defined by gender and the number of weeks.
      RESULTS: Percentile curves were built for 5, 10, 25, 50, 75, 90 and 95%
      percentiles for the newborn in the form of tables and graphs. CONCLUSIONS:
      Constructing birth-weight curves from data pertaining to the target population
      led to better classification of the newborn.

PMID- 17502960
TI  - [Household spending on private health care in Cartagena de Indias, 2004].
AB  - OBJECTIVE: Determining household out-of-pocket payments for access to health care
      services in Cartagena, Colombia, and its correlation with head of household
      characteristics (socioeconomic level, schooling, general social health security
      system (GSHSS) affiliation and type of work). METHODS: A cross-sectional study
      was carried out on a sample of 384 homes selected by using proportional
      stratified random sampling. Data was collected using a standardised form. SPSS
      (version 10.0) was used for statistical and econometric analysis. RESULTS: The
      lowest socioeconomic strata (1 and 2) were incurring higher out-of-pocket
      expenditure than higher strata (3-6). Other factors predicting greater
      expenditure on health compared to income were household heads' low level of
      schooling, being unemployed or working independently and the fact of not being
      affiliated to the GSHSS. CONCLUSIONS: Market mechanism expansion into the
      Colombian health system has resulted in greater inequality in terms of out-of
      pocket payment for the lowest social strata. Our findings suggest that the need
      for such financing represents an important barrier for gaining access to health
      care.

PMID- 17502961
TI  - [Equity in access to health-services in Antioquia, Colombia].
AB  - OBJECTIVE: Analysing equity in access to health care in Antioquia, Colombia.
      METHODS: Poorer and richer groups' access to health-care was evaluated, as was
      that of people with insurance and those without it. A Logit model was estimated
      for analysing the main determinants of access to curative and preventative health
      care services; explanatory variables were socioeconomic status, education level,
      self-reported health status, age, gender, urban/rural location and social
      security affiliation. RESULTS: There was no difference in health-care service
      access amongst people affiliated to contribution-based and subsidised regimes.
      However, financial constraints represented important obstacles for subsidised
      regime members and those having no affiliation. Contribution-based regime members
      had greater resources for continuing to receive attention. There was positive
      bias in using preventative services thereby favouring people having higher
      socioeconomic status. CONCLUSIONS: Educational level, age and being affiliated to
      social security were the main factors explaining health-care service access.
      Gender, self-reported health status and geographical location were additional
      factors explaining preventative health-service access.

PMID- 17502962
TI  - [Caregivers and health workers' perceptions of neonatal disease alarm signals in
      Guapi, Colombia].
AB  - OBJECTIVES: Exploring caregivers (CG) and health workers' (HW) perceptions of
      danger signals in the newborn and establishing the type of medical attention they
      require in rural and urban areas of Guapi on Colombia's Pacific coast. METHODS: A
      descriptive design was used combining qualitative and quantitative methods. Three
      focus groups, three semi-structured interviews and two case-studies were
      employed. Some signals obtained from these data were used for constructing a
      structured interview. A survey was carried out with 200 CGs (mothers with
      newborn, grandmothers, community mothers, housewives) and 40 HWs (general
      practitioners, health promoters, nursing auxiliaries, traditional medicine
      healers, midwifes and FAMI-mothers). The data was analysed using MaxQDA 2.0
      qualitative data software and ethnographic analysis. RESULTS: The first 5 signs
      of illness (in order of importance) perceived by CGs and HWs were: diarrhoea,
      dehydration, fever, vomiting and breathing problems. They coincided in their
      perceptions of the need for emergency consultation for convulsions, tetanus and
      dehydration. Significant differences were found between HW and CG perceptions
      regarding "type of consultation" for dehydration, fever, convulsions, breathing
      problems and tetanus (p<0.05). Cultural illnesses (i.e. the evil eye and ghosts)
      also emerged. CONCLUSIONS: CGs and HWs in Guapi were good at recognising danger
      signals for neonatal illness; however, there were differences regarding the
      search for attention. The finding of cultural illnesses must be taken into
      account in newborn attention strategies. This acceptable level of recognition was
      hindered by the lack of quality medical care services for the newborn
      encountering health problems.

PMID- 17502963
TI  - [Clinical and epidemiological characterisation of dengue haemorrhagic fever in
      Neiva, Colombia, 2004].
AB  - OBJECTIVE: Neiva (a southern Colombia city) is endemic for dengue fever and
      dengue haemorrhagic fever. Neiva has suffered outbreaks of dengue, that in 2004
      being the latest one. This study was designed to characterise epidemiological and
      clinical data from that outbreak of dengue. MATERIAL AND METHODS: This was a
      descriptive, retrospective study of children aged less than 13 years who were
      admitted to the University Hospital and fulfilled the WHO's clinical and
      laboratory criteria for dengue or dengue haemorrhagic fever. Demographic,
      clinical and paraclinical data were recorded and analysed using Chi square
      (chi(2)) bivariate tabular test. RESULTS: 105 children were diagnosed as
      suffering from either dengue haemorrhagic fever (87.6%) or dengue fever (12.4%);
      67% of them were aged less than 5 years. Girls were more frequently affected by
      severe clinical manifestations. 83% of the children were admitted during the
      first six days of the disease; dengue shock syndrome was diagnosed in 20% and 76%
      presented clinical complications (chi(2) 29.53, gl 6, p=0.0000).
      Aminotransferases were 3 to 5 times above normal levels. There was a statistical
      correlation between low platelet count (less than 20 000 per mm(3)) and shock
      during admission (chi(2) 20.65, gl 4, p=0.0004). Complications arose during
      clinical evolution in 32% of the cases (13% myocarditis, 19% hepatitis or
      encephalitis and 2% sepsis). CONCLUSION: The clinical and epidemiological
      characteristics observed in this cohort evidenced differences in age, gender and
      organs affected compared to data described in the literature; there was a high
      incidence of myocarditis.

PMID- 17502964
TI  - [Cardiovascular disease risk factors in people working at a Colombian health
      institution].
AB  - OBJECTIVE: Establishing the prevalence of recognised biological and behavioural
      cardiovascular disease (CVD) risk factors in a population of workers at a health
      institution in Popayan, Colombia. METHODS: An observational descriptive study was
      conducted, 96 employees being interviewed to obtain information regarding their
      socio-demographic characteristics, tobacco and alcohol consumption, physical
      activity, eating habits and personal and family history of CVD. Each worker's
      standardised glycaemia, serum lipids, arterial blood pressure and body mass index
      were measured. RESULTS: There was 12,5% behavioural risk factor prevalence for
      smoking, 58,3 % for alcohol consumption, 56,3 % physical inactivity during free
      time and 82,3 % atherogenic diet; biological risk factor prevalence was 11,5 %
      hypertension, 45,8 % being overweight, 1 % diabetes, 61,5 % dyslipidaemia and
      58,3 % family history of CVD. It was also found that the risk of hypertension was
      significantly higher in males, in individuals >40 years, in people having >25 BMI
      and in smokers. Regarding dyslipidaemia, the risk was higher in males and in >40
      year old individuals. The risk of being overweight and obese was significantly
      associated with smoking and alcohol consumption. CONCLUSION: Although this is an
      institution having an asymptomatic and relatively young population (25-55 years),
      action should be taken towards modifying lifestyles to reduce CVD risk in the
      affected population due to the high prevalence of biological and behavioural risk
      factors.

PMID- 17502965
TI  - [Environmental tobacco smoke and pneumonia in children living in Monterrey,
      Mexico].
AB  - OBJECTIVE: Acute respiratory diseases occupy the first 5 places in infantile
      morbidity and mortality around the world, two million children directly dying
      from such cause annually. Environmental tobacco smoke (ETS) contains toxic and
      irritating compounds having an injurious effect on health, producing increased
      risk of morbidity and mortality in non-smoking adults and children. Our main
      objective was determining the association between ETS and pneumonia in children.
      MATERIAL AND METHODS: This was an unmatched case and controls hospital-based
      study. Odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS:
      A total of 285 patients (142 cases and 143 controls) were studied; 47,4 % of the
      patients were female and average age was 4,5,+2,7. OR for patients being exposed
      to ETS developing pneumonia was 3,44 (CI: 2,11-5,6). DISCUSSION: Children being
      exposed to ETS increases the risk of developing pneumonia by more than threefold.

PMID- 17502966
TI  - [Sexually-transmitted infection in a high-risk group from Monteria, Colombia].
AB  - OBJECTIVE: Identifying the main aetiological agents of sexually transmitted
      infections (STI) in a high-risk population from the city of Monteria, Colombia.
      METHODOLOGY: The population consisted of 69 sex-workers (high-risk group) and 16
      housewives (low-risk group) living in the city of Monteria. Specimens were
      cultured by standard microbiological methods and by the AMPLICOR CT/NG molecular
      technique. RESULTS: Patients were aged 18-44 (26.1 average age). It was
      determined that 17,4% of the high-risk population were positive for G. vaginalis,
      15,9 % for C. trachomatis, 4,3 % for N. gonorrhoeae and 2,9 % for T. vaginalis
      and Candida albicans and, in the low-risk population, 56,3 % for G. vaginalis,
      12,5 % for C. trachomatis, 6,3 % for N. gonorrhoeae and 12,5 % for C. albicans.
      It was found that 70 % of the sex-workers had 5-10 sexual relationships per week,
      10 % 11-15 per week and 20 % 16-20 per week (average above 1 000 annual
      partners). 15,4 % of the sex-workers did not use protection during their sexual
      relationships. CONCLUSIONS: The high rates of infection found in the populations
      studied presume a high risk of transmission, making it a priority to intervene in
      these groups to prevent the spread of HIV and STI.

PMID- 17502967
TI  - [Mycobacteria-HIV/AIDS association in patients attending a teaching-hospital in
      Bogota, Colombia].
AB  - OBJECTIVE: Evaluating the frequency of mycobacterium infection in an HIV-positive
      population and its influence on medium-term survival, along with clinical and
      epidemiological factors associated with co-infection. METHODS: Several clinical
      specimens were studied for mycobacteria in a sample of 92 HIV+ patients at the
      San Juan de Dios teaching-hospital in Bogota, Colombia, during 1996. Factors
      associated with infection were measured using a prevalence ratio (PR), CI=95%,
      and logistic regression was used in the multivariable models. The likelihood of
      survival for three months was measured using Kaplan-Meir curves and factors
      associated with survival were assessed using Rate ratios and Cox's model.
      RESULTS: Eight percent of the patients had tuberculosis and 6% of them were found
      to be infected with atypical mycobacterium. Mycobacterium avium complex (MAC) was
      the most frequent species, followed by M. fortuitum and M. chelonae. Mixed
      infections with M. tuberculosis and MAC were diagnosed in one patient and two
      different species of atypical mycobacterium were isolated in other two cases.
      Patients suffering from tuberculosis and stages III or IV HIV infection had a 16%
      survival rate. CONCLUSIONS: Tuberculosis-HIV/AIDS frequency and atypical
      Mycobacterium-HIV/AIDS' association were very similar. The most frequently
      isolated atypical mycobacterium specie in this study was MAC. Survival rate was
      lower for patients infected by M. tuberculosis and even lower when a multi
      resistant strain was involved. The most important clinical factor associated with
      M. tuberculosis was the presence of fever and loss of weight with mycobacterial
      infection. Blood provided the best samples for isolating mycobacteria.

PMID- 17502968
TI  - [Evaluating two pyrethroids in dengue vector control in Putumayo, Colombia].
AB  - OBJECTIVE: Evaluating the efficacy of two pyrethroid insecticides on Aedes
      aegypti, thereby providing useful information for decision-making in controlling
      dengue. METHODS: The effect on A. aegypti of ultra low volume (ULV) highcis
      Permethrin (Depe) and ss-cypermethrin pyrethroids in a smoke-generating
      formulation (Bolate) was evaluated in 16 blocks in the town of Puerto Leguizamo,
      Putumayo, between July and December 2004. Their efficacy was measured by the
      mortality of mosquitoes kept in sentinel cages set in different parts of the
      households and weekly follow-up of the number of mosquitoes and the presence of
      larvae. RESULTS: There was an 80% reduction in mosquito density on the day after
      insecticide treatment for both insecticides. Mosquitoes became displaced from
      inside the houses to outside them after the insecticides had been applied. In
      spite of the insecticides' immediate impact, a maintained reduction in mosquito
      density throughout the 5 weeks' evaluation was not observed, probably due to the
      emergence of adults from deposits which had not been treated. CONCLUSION: These
      insecticides showed higher than 80% efficacy in reducing A. aegypti mosquito
      density and they constitute an alternative for dengue control.

PMID- 17502969
TI  - [Modelling epidemics: the case of severe acute respiratory syndrome in Canada].
AB  - OBJECTIVE: Severe acute respiratory syndrome propagation in Canada during 2003 is
      analysed by means of simple models, comparing the influence of isolation measures
      on two epidemic waves. METHODS: Deterministic susceptible-infected and
      susceptible-infected-removed models were used for both epidemic waves, using
      official published information. NLREG 6.2 was used for estimating deterministic
      parameters and analytical solutions were obtained with Maple 9 software.
      Dynamical indicators were obtained for the epidemic. RESULTS: Suitable adjustment
      of the data was observed with both models, but smaller adjustment was observed
      during the second wave with the non- removed model. The highest rate of
      infectiousness was shown (35 new cases per 10 000 susceptible people) during the
      second wave (with R0 near to one), in spite of presenting greater incidence (8.8
      cases per day), compensated for by a high rate of removal (11,5 cases per day)
      which lasted less than the epidemic (11,1 days), and a lower rate of attack (1
      case per each 100 susceptible people). CONCLUSIONS: The susceptible-infected
      model can be useful during an epidemic's initial phase (prior to removal);
      however, closer monitoring of an epidemic's development is required for modelling
      the strength of removal and deriving useful information for decision-making.

PMID- 17502970
TI  - [Displaced and local children's alimentary patterns and nutritional state in
      Piedecuesta, Colombia].
AB  - OBJECTIVES: This study was aimed at establishing displaced and local children's
      alimentary patterns amongst the school-age population from the Guatiguara area
      (Piedecuesta) and correlating their nutritional state with chosen socioeconomic
      and nutritional factors. METHODS: This descriptive transversal study of 89
      displaced and local school-aged children (6 to 12 years of age) from the
      Guatiguara area (population=258) was carried out in 2004. Data was collected from
      socio-demographic and nutritional surveys as well as a food intake questionnaire
      (SICI). Twenty-four hour dietary recall, standardised kitchen item games and
      photographic models of the size of food portions were also used. The children's
      height and weight were measured. SICI, Excel, Epi Info 6.04d and Stata 8.0
      software were used for processing the data. RESULTS: Nutritional state (weight
      per age - W/A) was as follows: 25,8 % deficit and 14,6 % risk of deficit. Low
      vegetable, fruit and protein consumption was found. The lowest percentages
      regarding consumption of needed items pertained to calcium, vitamin B6, iron,
      zinc and niacin. The relationship between receiving a monthly family income of
      less than Col $150 000 and nutritional deficit was (OR=2.76 CI(95 %) 0,92-8,44,
      p=0,040). Nutritional deficit protection factors consisted of having an employed
      mother (OR=0.29 CI(95 %) 0,09-0,84, p=0,012) and families having 2 or 3 employed
      members covering household expenses (OR=0.17 CI(95 %) 0,03-0,69 p=0,0052).
      CONCLUSION: Selected socioeconomic factors influenced the studied population's
      alimentary pattern and nutritional state.

PMID- 17502971
TI  - [Public health: knowledge, practice and training].
AB  - This paper presents a discussion regarding Public Health's main challenges:
      knowledge of it, professional practice and training human resources. It begins by
      recognising Latin-America's unequal and polar socio-sanitary context and the
      sanitary field's myriad single referents, paying special attention to essential
      public health functions, the Millennium development goals and the Latin-American
      Association of Public Health Education. Emphasis is placed on three components:
      knowledge of public health (levels, domains, disciplines, temporality, dimensions
      and complexity), social practice (state-public, collective general practice and
      group professional practice) and human resources' training (professional,
      technical, training and up-dating). An essential challenge is then identified for
      each of these components and a set of proposals to be launched from the Latin
      American Association of Public Health Education is outlined (interchange,
      partnerships and advocacy).

PMID- 17502973
TI  - Schizophrenia in Turkish newspapers : retrospective scanning study.
AB  - The attitude of mass media is a strong determinant for stigmatisation since the
      majority of the society gets exposed to psychiatric disorders via either written
      or visual media. In this study we explored to demonstrate the meaning attributed
      to the word schizophrenia in Turkish written printed media. We screened the
      online sites of 12 national newspapers which allow word scanning between the
      dates January 1, 2001 and May 1, 2006. The searched terms appeared in a total of
      878 texts. In all twelve newspapers, the terms "Schizophrenia", "Schizophrene",
      or "Schizophrenic" appeared once every 2.2 days. While a positive referral
      appeared once in every 12.2 days, a negative referral or metaphoric use was seen
      once every 3.1 days. Among the 878 texts scanned, in 491(55.9%) the searched
      terms appeared with reference to the disease and in 387 (44.1%) the searched
      terms were used metaphorically. Considering the assumption the negative reporting
      may have a stronger impact than positive reporting, it is possible to suggest
      that Turkish newspapers are raising stigmatisation. It is meaningful that the
      name of a disease is used almost with equal frequency as a metaphoric term. In
      our study, higher rates of metaphoric use observed can be explained with the fact
      that in Turkey the word Schizophrenia is attributed with strong negative
      perception.

PMID- 17502972
TI  - Evaluation of a xenogeneic VEGF vaccine in dogs with soft tissue sarcoma.
AB  - Active immunization against pro-angiogenic growth factors or their receptors is
      an emerging strategy for controlling tumor growth and angiogenesis. Previous
      studies in rodent tumor models have indicated that immunization against
      xenogeneic growth factors is more likely to induce effective anti-tumor responses
      than immunization against the autologous growth factor. However, the
      effectiveness or safety of the xenogeneic vaccination approach has not been
      previously assessed in a clinically relevant outbred, spontaneous tumor model.
      Therefore, we investigated the safety and anti-tumor and anti-angiogenic effects
      of a xenogeneic vascular endothelial cell growth factor (VEGF) vaccine in pet
      dogs with spontaneous cancer. Nine dogs with soft tissue sarcoma were immunized
      with a recombinant human VEGF vaccine over a 16-week period. The effects of
      immunization on antibodies to human and canine VEGF, circulating VEGF
      concentrations, tumor microvessel density (MVD), and tumor growth were assessed.
      The xenogeneic VEGF vaccine was well-tolerated by all dogs and resulted in
      induction of humoral responses against both human and canine VEGF in animals that
      remained in the study long enough to receive multiple immunizations. Three of
      five multiply immunized dogs also experienced sustained decreases in circulating
      plasma VEGF concentrations and two dogs had a significant decrease in tumor MVD.
      The overall tumor response rate was 30% for all treated dogs in the study. We
      conclude therefore that a xenogeneic VEGF vaccine may be a safe and effective
      alternative means of controlling tumor growth and angiogenesis.

PMID- 17502974
TI  - Psychosis and adults with intellectual disabilities. Prevalence, incidence, and
      related factors.
AB  - OBJECTIVE: To determine the point prevalence, incidence, and remission over a 2
      year period of psychosis in adults with intellectual disabilities, and to
      investigate demographic and clinical factors hypothesised to be associated with
      psychosis. METHOD: A population-based cohort of adults with intellectual
      disabilities (n = 1,023) was longitudinally studied. Comprehensive face-to-face
      mental health assessments to detect psychosis, plus review of family physician,
      psychiatric, and psychology case notes were undertaken at two time points, 2
      years apart. RESULTS: Point prevalence is 2.6% (95% CI = 1.8-3.8%) to 4.4% (95%
      CI = 3.2-5.8%), dependant upon the diagnostic criteria employed. Two-year
      incidence is 1.4% (95% CI = 0.6-2.6), and for first episode is 0.5% (95% CI = 0.1
      1.3). Compared with the general population, the standardised incidence ratio for
      first episode psychosis is 10.0 (95% CI = 2.1-29.3). Full remission after 2 years
      is 14.3%. Visual impairment, previous long-stay hospital residence, smoking, and
      not having epilepsy were independently associated with psychosis, whereas other
      factors relevant to the general population were not. CONCLUSIONS: The study of
      psychosis in persons with intellectual disabilities benefits the population with
      intellectual disabilities, and advances the understanding of psychosis for the
      general population. Mental health professionals need adequate knowledge in order
      to address the high rates of psychosis in this population.

PMID- 17502975
TI  - Belief models in first episode schizophrenia in South India.
AB  - BACKGROUND: Existing evidence indicates that dissonance between patients' and
      professionals' explanatory models affects engagement of patients with psychiatric
      services in Western and non-Western countries. AIMS: To assess qualitatively the
      explanatory models (EMs) of psychosis and their association with clinical
      variables in a representative sample of first episode patients with schizophrenia
      in South India. METHOD: One hundred and thirty one patients with schizophrenia
      presenting consecutively were assessed. Measures included the patient's
      explanatory models, and clinician ratings of insight, symptoms of psychosis, and
      functioning on standard scales. RESULTS: The majority of patients (70%)
      considered spiritual and mystical factors as the cause of their predicament; 22%
      held multiple models of illness. Patients who held a biomedical concept of
      disease had significantly higher scores on the insight scale compared to those
      who held non-medical beliefs. Multivariate analyses identified three factors
      associated with holding of spiritual/mystical models (female sex, low education
      and visits to traditional healers); and a single factor (high level of insight)
      for the endorsement of biological model. CONCLUSIONS: Patients with schizophrenia
      in this region of India hold a variety of non-medical belief models, which
      influence patterns of health seeking. Those holding non-medical explanatory
      models are likey to be rated as having less insight.

PMID- 17502976
TI  - A longitudinal study of acculturative stress and homesickness: high-school
      adolescents immigrating from Russia and Ukraine to Israel without parents.
AB  - BACKGROUND: Acculturative stress and homesickness are psychological reactions to
      cross-cultural transition. They may cause a decline in social functioning,
      increased psychological distress, and, in severe cases, psychiatric disorders
      among immigrants. AIM: This study examined changes in acculturative stress and
      homesickness over the first 3 years in the host country. It also investigated the
      role of pre-migration psychological resources, perceived discrimination, and
      perceived social support as predictors of acculturative stress and homesickness.
      METHOD: 211 high-school adolescents who immigrated from Russia and Ukraine to
      Israel without parents participated in the study. They filled out self-report
      questionnaires at four times: about half a year before emigration and during the
      three consecutive years after immigration. RESULTS: Acculturative stress
      strengthened in the second year compared to the first year and decreased in the
      third year after immigration. Homesickness decreased from the first to the third
      year after immigration. Pre-migration psychological resources were negatively
      correlated with acculturative stress and homesickness. Perceived discrimination
      was positively correlated with acculturative stress and homesickness. Perceived
      social support from friends and teachers negatively correlated with acculturative
      stress and homesickness, while perceived social support from the adolescents'
      parents was not correlated with these variables. CONCLUSION: Personal
      psychological resources and social support buffer acculturative stress and
      homesickness in immigrants, while discrimination aggravates their distress.

PMID- 17502977
TI  - Do symptom dimensions or categorical diagnoses best discriminate between known
      risk factors for psychosis?
AB  - OBJECTIVE: To describe symptom dimensions of psychosis using detailed
      psychopathological information from epidemiologically defined incident cases
      which include the full spectrum of functional psychosis across all age ranges.
      Then, assess the comparative usefulness of the dimensional and categorical
      representations of psychosis in discriminating between demographic and pre-morbid
      risk factors. METHOD: A total of 464 incident cases of psychosis assessed with
      OPCRIT (Operational Checklist for Psychotic Symptoms) were included in an
      exploratory factor analysis. Using Regression analyses we modelled the
      associations of the dimensional and categorical representations of psychosis with
      antecedent validating variables and compared the subsequent models using the
      likelihood ratio test. RESULTS: Factor analysis produced five-symptom dimensions,
      manic, disorganisation, depressive, delusional and auditory hallucinatory
      symptoms, explaining 58% of the total variance. Different dimensions were
      differentially associated with the pre-morbid risk factors. Neither the
      dimensional nor the categorical representations on their own were sufficient to
      explain associations with the antecedent validating variables. CONCLUSION:
      Neither the dimensional or the diagnostic representation of psychosis was
      superior in discriminating between known risk factors, combining dimensional
      measures with categorical diagnoses will probably be more informative in
      determining the causes and correlates of psychosis.

PMID- 17502978
TI  - The impact of process variables on the removal of PBDEs and NPEOs during
      simulated activated sludge treatment.
AB  - This work illustrates that the removal of some endocrine-disrupting compounds
      from sewage treatment works effluent is dependent on parameters such as sludge
      age, influent concentrations, concentrations of co-pollutants and hydraulic
      retention time as well as physicochemical properties of the compound. Greater
      nonylphenol polyethoxylates (NPEO) and polybrominated diphenyl ether (PBDE)
      removal was observed at a higher sludge age, and it appeared that the enzymes
      required for NPEO degradation were already present. NPEO degradation was reduced
      in the presence of the more hydrophobic PBDE compounds as sorption of PBDEs
      occurred, rapidly reducing available sorption sites for NPEOs. The more
      hydrophobic NP and PBDEs demonstrated little degradation in comparison to longer
      chain NPEO compounds. From this research, it is apparent that the principal
      environmental risk of PBDE contamination after wastewater treatment is via sludge
      disposal routes. Treatment of wastewater containing NPEO surfactants poses
      environmental risks via two routes: some nonylphenolic compounds may pass through
      into receiving waters and degradation products such as nonylphenol and short
      chain ethoxylate compounds will enter the environment via sludge disposal.

PMID- 17502979
TI  - Role of temperature and hydrochloric acid on the formation of chlorinated
      hydrocarbons and polycyclic aromatic hydrocarbons during combustion of paraffin
      powder, polymers, and newspaper.
AB  - Formation of chlorinated hydrocarbons and polycyclic aromatic hydrocarbons (PAHs)
      were determined using a laboratory-scale incinerator when combusting materials at
      different temperatures, different concentrations of hydrochloric acid (HCl), and
      when combusting various types of polymers/newspaper. Polychlorobenzenes (PCBz),
      polychlorophenols (PCPhs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and
      their toxic equivalency (TEQ) and PAHs were highlighted and reported. Our results
      imply maximum formation of chlorinated hydrocarbons at 400 degrees C in the
      following order; PCBz>or=PCPhs>>PCDFs>PCDDs>TEQ on a parts-per-billion level.
      Similarly, a maximum concentration of chlorinated hydrocarbons was noticed with
      an HCl concentration at 1000 ppm with the presence of paraffin powder in the
      following order; PAHs>PCBz>or=PCPhs>>PCDFs>PCDDs>TEQ an a parts-per-billion
      level. PAHs were not measured at different temperatures. Elevated PAHs were
      noticed with different HCl concentrations and paraffin powder combustion (range:
      27-32 microg/g). While, different polymers and newspaper combusted, nylon and
      acrylonitrile butadiene styrene (ABS) produced the maximum hydrogen cyanide (HCN)
      concentration, concentrations of PCDD/FS, dioxin-like polychlorinated biphenyls
      (DL-PCBs), and TEQ were in a decreasing order: polyvinylchloride
      (PVC)<newspaper<polyethyleneterephthalate (PET)< polyethylene (PE)< polypropylene
      (PP)< ABS = blank. Precursors of PCBs were in a decreasing order:
      PP<nylon<PE<newspaper<ABS<PVC<blank<PET. Precursors of PCDD/Fs were in a
      decreasing order: newspaper <PP=nylon<PE<ABS<PVC= blank<PET. BTX formation was in
      a decreasing order; PE<nylon<newspaper<ABS<PP. PAHs formation were elevated with
      parts-per-million levels in the decreasing order of
      PP<nylon<PE<newspaper<blank<ABS< PET<PVC.

PMID- 17502980
TI  - Biomarkers study for sediment quality assessment in spanish ports using the crab
      Carcinus maenas and the clam Ruditapes philippinarum.
AB  - Intermolt crab Carcinus maenas and clam Ruditapes philippinarum were used to
      determine the toxicity of sediments collected in four Spanish ports (Cadiz,
      Huelva, Pasajes, and Bilbao) under laboratory conditions during 28 days. Sediment
      samples were analyzed to determine chemical concentration of metals (As, Cd, Cr,
      Cu, Fe, Hg, Mn, Ni, Pb, and Zn), polyaromatic hydrocarbons, polychlorinated
      biphenyls, grain size distribution, and organic matter content. Different
      biomarkers of exposure of early biological stress were determined after 28-day
      exposure in crabs and clams, in the hepatopancreas and in the digestive gland,
      respectively: metallothionein, ethoxyresorufin O-deethylase (EROD), glutathione
      peroxidase (GPX), glutathione S-transferase (GST), and glutathione reductase
      activities (GR). The battery of biomarkers tested resulted in showing and linking
      the bioavailability of various contaminants and sediment characteristics to the
      toxicity of the different sediments. Significant induction of MTs was observed
      when organisms were exposed to metal-contaminated sediments (port of Huelva), and
      induction of EROD and GPX activities after exposure to sediments containing
      organic compounds (port of Bilbao and Pasajes). Higher induction was shown in
      biomarkers tested in crabs; nevertheless, only interspecies significant
      differences were observed in the induction of GR and GST activities. The present
      work confirms the necessity of using species with different ecological lifestyles
      for sediment toxicity assessment and validates the use of this set of biomarkers
      as a potential tool in sediment toxicity assessment.

PMID- 17502981
TI  - ACTH-independent macronodular adrenal hyperplasia: imaging findings of a rare
      condition : A case report.
AB  - Endogenous Cushing's syndrome is a relatively rare disease. Most cases being ACTH
      dependent, ACTH-independent Cushing's syndrome (AICS) is an even rarer condition
      [15%-20%]. In more than 95% cases the cause of AICS is unilateral adrenal
      enlargement caused by adenoma or carcinoma. Bilateral adrenal disease is caused
      by primary pigmented nodular adrenal dysplasia (PPNAD) and ACTH-independent macro
      nodular hyperplasia (AIMAH). Only few case reports of the latter condition exist
      in the radiology literature, PPNAD being the commoner of two as the cause for
      AICS.

PMID- 17502982
TI  - Acute necrotizing pancreatitis: role of CT-guided percutaneous catheter drainage.
AB  - Necrotizing pancreatitis is the most severe form of acute pancreatitis associated
      with high morbidity and mortality. Percutaneous CT-guided catheter drainage is an
      important treatment option that can be effective whether used alone, or as an
      adjunct to operation. Existing literature describing the role of percutaneous
      catheter drainage of necrotizing pancreatitis is limited. This update reviews
      techniques, indications, outcomes, and complications of CT-guided percutaneous
      treatment of acute necrotizing pancreatitis.

PMID- 17502983
TI  - The mendosal suture of the occipital bone: occurrence in Indian population,
      embryology and clinical significance.
AB  - The occipital bone is ontogenetically and functionally unique when compared to
      the other bones of the skull in humans and other mammalian cousins. The occipital
      bone develops from six ossification centers; any defect in the ossification
      process will give rise to mendosal suture (accessory suture) and conditions like
      posterior plagiocephaly. There is a paucity of literature regarding the mendosal
      suture and further more, its report in Indian population is not known. The
      present study was conducted to find out the occurrence of mendosal suture in the
      Indian dry skulls. Fifteen specimens (3%) were found to have these sutures out of
      five hundred (500) skulls examined. Nine (3.1%) samples are of male skulls out of
      two hundred ninety (290) and six (2.85%) samples are that of female skulls out of
      two hundred ten (210). The mendosal suture ran close to the superior nuchal line
      in all specimens and traveled medially from the lambdoidal suture. The length of
      the sutures ranged from 0.8 cm to 2.6 cm (1.88 cm) on the right side and 1.4 cm
      to 2.9 cm (1.94 cm) on the left side respectively in male skulls; and 0.7 cm to
      2.8 cm (1.55 cm) on the right side and 1 cm to 2.4 cm (1.42 cm) on the left side,
      respectively, in female skulls. The origin of mendosal suture from the lambdoidal
      suture was 5.7 cm to -6.3 cm (5.98 cm) from the tip of the mastoid process on the
      right side and 5.6 to -6.3 cm (6 cm) on the left side, respectively, in male
      skulls; and 5.4 cm to -5.8 cm (5.58 cm) on the right side and 5.4 cm to -5.6 cm
      on the left side respectively in female skulls. The occurrence and clinical
      significance of the present study is discussed.

PMID- 17502984
TI  - Extensor retinaculum syndrome after distal tibial fractures: anatomical basis.
AB  - Fractures of the distal extremity of the tibia include physeal injuries among
      teenagers and more complex fractures among adults. Displacement causes the
      compression of the muscles located between the distal tibia and the superior
      extensor retinaculum (SER). Among the muscles of anterior compartment of the leg,
      the extensor hallucis longus (EHL) is particularly vulnerable due to the amount
      of muscle fibers extending under the SER. Consequently, a partial anterior
      compartment syndrome could result, affecting only the distal portion located
      under the SER. In clinical practice, Mubarak measured the intramuscular pressure
      isolated under the SER and suggested the physio-pathological hypothesis of a
      compression of distal muscle fibers. The aim of this study is to compare the
      ratios of anterior compartment muscle fibers extending under the SER. Twenty legs
      were dissected in order to study how much of these muscles extend under the SER,
      their passages possibly dividing into two of the SER, as well as their
      vascularization and their innervation. On the last seven legs, the engagement of
      the muscles were measured in the spontaneous position and with a dorsal flexion
      of 0 degrees . The posterior muscle fibers of this compartment always descend
      lower than the anterior fibers. EHL muscle fibers and those of the inconsistent
      fibularis tertius always extend under the retinaculum, unlike those of the
      tibialis anterior and of the extensor digitorum longus. The EHL muscle extends
      under the SER more than the other muscles. Its posterior fibers are longer when
      this muscle goes through a dividing into two of the retinaculum. Its
      vascularization seems lesser, which could explain why this muscle tends to suffer
      more. The deep fibular nerve innervates the anterior compartment of the leg, yet
      no nerve branches can be found under the upper edge of the retinaculum. In all
      cases, the muscle fibers do not extend as much under the SER in a 0 degrees of
      dorsal flexion. This anatomical study allows us to explain why the EHL is more
      likely to suffer from this partial compartment syndrome and confirms that when
      the latter occurs it is necessary, in all cases, to do emergency surgery opening
      the distal crural fascia and necessarily including the SER.

PMID- 17502986
TI  - Risk factors for ulnar nerve compression at the elbow: a case control study.
AB  - BACKGROUND: Ulnar nerve compression at the elbow is frequently encountered as the
      second most common compression neuropathy in the arm. As dexterity may be
      severely affected, the disease entity can seriously interfere with daily life and
      work. However, epidemiological research considering the risk factors is rarely
      performed. This study intended to investigate whether potential risk factors
      based on historical belief contribute to the development of ulnar nerve
      compression at the elbow. METHOD: A hospital based case control study was
      performed of patients that underwent surgical treatment for ulnar nerve
      compression at the elbow at the neurosurgical department from June 2004 until
      June 2005. Controls were those patients treated for a cervical or lumbar
      herniated disc. The main outcome measure was the presence of ulnar nerve
      compression at the elbow proven clinically, and electrodiagnostically. RESULTS:
      110 patients with ulnar nerve lesions and 192 controls were identified. Smoking,
      education level and related working experience were identified as risk factors.
      Conversely, gender, BMI, alcohol consumption, trauma to the elbow, diabetes
      mellitus, and hypertension are not risk factors for the development of ulnar
      nerve compression at the elbow. CONCLUSION: Risk factors are clearly defined. In
      the past many factors have been described, but mostly in surgical series. This
      study concludes that gender, previous fracture of the elbow and BMI are not
      predictive factors for ulnar entrapment neuropathy. However, education and
      working experience are closely correlated with this entity.

PMID- 17502987
TI  - Complete resection of a cavernous haemangioma of the optic nerve, the chiasm, and
      the optic tract.
AB  - The involvement of the optic nerve, the chiasma, and the optic tract by a
      cavernoma has been reported in only three patients. In all of them, a biopsy of
      the vascular lesion was obtained. We report a further example of a 38-year-old
      male patient who suffered from acute onset of severe headache and progressive
      loss of vision. The vascular malformation of the optic pathways was completely
      removed via a pterional approach. This is the first reported instance of complete
      resection of a cavernoma involving the optic nerve, the chiasm, and the optic
      tract.

PMID- 17502988
TI  - Olfactory schwannoma.
AB  - We report a case of olfactory schwannoma with calcification. Intraoperative
      findings indicated that the tumour originated from the olfactory groove.
      Intraoperative findings of previous studies have not indicated a clear
      relationship between subfrontal schwannoma and the olfactory nerve, which seems
      strange, given the association between tumours and cranial nerves at other sites.
      We suggest this observation has not been reported because the growing olfactory
      schwannoma changes the local morphology, affecting the appearance of the
      olfactory nerve.

PMID- 17502989
TI  - Neurinoma of the hypoglossal nerve in the submandibular space: case report and
      review of the literature.
AB  - Neurinomas of the hypoglossal nerve extending extra-cranially are rare; a
      schwannoma in a 63-year-old woman causing nerve palsy is reported. The tumour
      presented as a slow-growing mass in the right submandibular space; a surgical
      approach with transcervical exploration was performed. The post-operative course
      was uneventful.

PMID- 17502990
TI  - Effect of restriction endonucleases on assessment of biodiversity of cultivable
      polar marine planktonic bacteria by amplified ribosomal DNA restriction analysis.
AB  - To choose a suitable restriction endonuclease for quick assessment of bacterial
      diversity in polar environments by ARDRA, we investigated the effect of
      restriction enzymes on ARDRA patterns of cultivable marine planktonic bacteria
      isolated from polar region. Thirty-three isolates were analyzed by ARDRA using
      five enzymes (HinfI, HaeIII, AluI, and the mix AfaI/MspI), respectively,
      resulting in different groups, each group corresponding to a particular genotype.
      A comparison of the ARDRA patterns was carried out, and phylogenetic position of
      all thirty-three bacteria was obtained by 16S rDNA sequencing. Consistent with
      phylogenetic analysis, ARDRA pattern comparison revealed that AluI, being
      sensitive and reliable enough to generate species-specific patterns, was a
      suitable restriction enzyme used for evaluating bacterial diversity, suggesting a
      combination of ARDRA with AluI and 16S rDNA sequencing can provide a simple, fast
      and reliable means for bacterial identification and diversity assessment in polar
      environments.

PMID- 17502991
TI  - Retinoblastoma and mental retardation microdeletion syndrome: clinical
      characterization and molecular dissection using array CGH.
AB  - We describe three patients with retinoblastoma, dysmorphic features and
      developmental delay. Patients 1 and 2 have high and broad forehead, deeply
      grooved philtrum, thick anteverted lobes and thick helix. Patient 1 also has
      dolicocephaly, sacral pit/dimple and toe crowding; patient 2 shows intrauterine
      growth retardation and short fifth toe. Both patients have partial agenesis of
      corpus callosum. Patient 3 has growth retardation, microcephaly, thick lower lip
      and micrognathia. Using array-comparative genomic hybridization (CGH), we
      identified a 13q14 de novo deletion in patients 1 and 2, while patient 3 had a
      7q11.21 maternally inherited deletion, probably not related to the disease. Our
      results confirm that a distinct facial phenotype is related to a 13q14 deletion.
      Patients with retinoblastoma and malformations without a peculiar facial
      phenotype may have a different deletion syndrome or a casual association of
      mental retardation and retinoblastoma. Using array-CGH, we defined a critical
      region for mental retardation and dysmorphic features. We compared this deletion
      with a smaller one in a patient with retinoblastoma (case 4) and identified two
      distinct critical regions, containing 30 genes. Four genes appear to be good
      functional candidates for the neurological phenotype: NUFIP1 (nuclear fragile X
      mental retardation protein 1), HTR2A (serotonin receptor 2A), PCDH8
      (prothocaderin 8) and PCDH17 (prothocaderin 17).

PMID- 17502992
TI  - Rituximab for treatment-resistant extensive Wegener's granulomatosis--additive
      effects of a maintenance treatment with leflunomide.
AB  - Extensive Wegener's granulomatosis (WG) is treated by glucocorticosteroids (GC)
      and cyclophosphamide (CYC). In some cases, the disease is refractory to CYC. For
      those patients the depletion of B-lymphocytes with rituximab is a promising new
      treatment modality. This is a retrospective study of six patients receiving
      rituximab (RTX) with 4 x 375 mg/m(2) body surface weekly because of inefficacy of
      CYC. Proteinase-3-antineutrophil cytoplasmic antibodies (PR3-ANCA) and c-ANCAs
      were assessed. For clinical follow-up the Birmingham Vasculitis Activity Score
      for WG (BVAS/WG) was used. In five of the six cases, leflunomide (LEF) was given
      as maintenance treatment. Mean follow up was 16 months (12-21 months). The median
      PR3-ANCA titer fell from 36.8 U/ml at baseline to 21.4 U/ml after 3 months, 8.3
      after 6 months, and 4.3 at month 12. The median BVAS/WG at baseline was 5 and 0
      after 1 month. Two minor relapses could be noticed at month 3. After 6 months,
      one patient still had a BVAS of 1, all the others had a BVAS of 0. At month 18, a
      major relapse occurred in one patient, which was successfully retreated with RTX.
      The RTX infusions were well tolerated. Rituximab is a well-tolerated, very
      effective medication for patients with Wegener's granulomatosis. Leflunomide
      maintenance may increase the efficacy of rituximab and prolong the disease-free
      period.

PMID- 17502993
TI  - Teneurins, a transmembrane protein family involved in cell communication during
      neuronal development.
AB  - Teneurins are a unique family of transmembrane proteins conserved from
      Caenorhabditis elegans and Drosophila melanogaster to vertebrates, in which four
      paralogs exist. In vertebrates, teneurin expression is most prominent in the
      developing brain. Based on their distinct, complementary expression patterns, we
      suggest a possible function in the establishment of proper connectivity in the
      brain. Functional studies show that teneurins can stimulate neurite outgrowth,
      but they might also play a role in axon guidance as well as in target recognition
      and synaptogenesis, possibly mediated by homophilic interactions. Though
      teneurins are transmembrane proteins, there is evidence that the intracellular
      domain has a nuclear function, since it can interact with nuclear proteins and
      influence transcription. Therefore, we speculate that teneurins might be
      processed by proteolytic cleavage (possibly regulated intramembrane proteolysis),
      which is triggered by homophilic interactions or, alternatively, by the binding
      of a still unknown ligand.

PMID- 17502994
TI  - Impaired apoptosis in lymphoblasts from Alzheimer's disease patients: cross-talk
      of Ca2+/calmodulin and ERK1/2 signaling pathways.
AB  - We have analyzed the intracellular signals that allow lymphoblasts from
      Alzheimer's disease (AD) patients to escape from serum deprivation-induced
      apoptosis. The following observations suggested that modulation of ERK1/2
      activity by Ca(2+)/calmodulin (CaM) is involved in preventing apoptosis: (i)
      ERK1/2 activity seems to support lethality in control cells, as PD98059, the
      inhibitor of the activating MEK prevented cell death; (ii) control cells show a
      persistent and higher stimulation of ERK1/2 than that of AD cells in the absence
      of serum; (iii) CaM antagonists have no effects on control cells, but sensitize
      AD cells to death induced by serum withdrawal and increased ERK1/2
      phosphorylation, and (iv) no apoptotic effects of CaM antagonists were observed
      in AD cells treated with PD98059. These results suggest the existence of an
      activation threshold of the ERK1/2 pathway setting by Ca(2+)/CaM-dependent
      mechanisms, which appears to be the critical factor controlling cell survival or
      death decision under trophic factor withdrawal.

PMID- 17502995
TI  - The adhesion GPCRs: a unique family of G protein-coupled receptors with important
      roles in both central and peripheral tissues.
AB  - G protein-coupled receptors (GPCRs) are a diverse superfamily of membrane-bound
      receptors. The second largest subgroup of GPCRs, the Adhesion GPCRs, has 33
      members in humans. Phylogenetic analysis of the entire repertoire of the seven
      transmembrane- domain (7TM) regions of GPCRs shows that the Adhesion GPCRs form a
      distinct family. Adhesion GPCRs are characterised by (1) long N termini with
      multiple functional domains often found in other proteins such as tyrosine
      kinases, integrins and cadherins, (2) highly complex genomic structure with
      multiple introns and splice variants and (3) a 7TM region that has no clear
      similarities with 7TM from other GPCRs. Several Adhesion GPCRs are known to have
      a role in the immune system but it is becoming more evident that many have
      important roles in the CNS. We speculate that the overall structural construction
      of the Adhesion GPCRs allows them to participate in different types of cell
      guidance.

PMID- 17502996
TI  - Hyaluronan.
AB  - The polysaccharide hyaluronan is an essential component of the vertebrate
      extracellular matrix and also produced by viruses, bacteria and fungi. Although
      the hyaluronan polymer is simply a disaccharide that repeats many thousands of
      times, it has an amazing array of biological functions and medical uses. For
      example, it is an efficient space filler that maintains hydration, serves as a
      substrate for assembly of proteoglycans and cellular locomotion, regulates
      cellular function and development, and is involved in tumor progression,
      inflammation and wound healing. Its physical properties and biocompatibility also
      make it of considerable importance in the development of engineered tissue,
      biomaterials and in clinical applications.

PMID- 17502997
TI  - Symptomatic central canal rupture heralding the presence of an asymptomatic conus
      dermoid.
AB  - Dermoid cysts represent a rare group of tumors manifesting predominantly in
      adulthood. Rupture of these tumors is well described with it being symptomatic
      more commonly intracranially as compared to central canal rupture of
      intraspinally located dermoid tumor which not only is uncommon, but also
      frequently asymptomatic. The authors report an unusual case of asymptomatic conus
      dermoid in a young male diagnosed when investigated for a symptomatic isolated
      central canal rupture. Fatty contents within the central canal may be a harbinger
      of an underlying dermoid tumor and a whole spine MRI should be performed in such
      cases to rule out this bizarre presentation.

PMID- 17502998
TI  - Polymorphisms in the matrix metalloproteinase-1, 3, and 9 promoters and
      susceptibility to adult astrocytoma in northern China.
AB  - The single nucleotide polymorphisms (SNPs) in the promoter region of matrix
      metalloproteinase (MMP) genes may influence tumor occurrence and progression via
      modifying mRNA transcription and protein expression. The study aims to explore
      the association of the SNPs in MMP-1, 3 and MMP-9 promoters with susceptibility
      to adult brain astrocytoma in northern China. Genotyping for the MMP-1 -1607
      2G/1G, MMP-3 -1171 5A/6A, and MMP-9 -1562 C/T SNPs were performed by PCR-RFLP
      methods among 236 adult astrocytoma patients and 366 healthy controls. The
      results showed that the overall distribution of the MMP-1 allelotype and genotype
      among astrocytoma patients and healthy controls was significantly different (P =
      0.002 and P < 0.001, respectively). Compared with the 2G/2G genotype, the 1G/1G
      genotype significantly decreased the risk of astrocytoma development (adjusted OR
      = 0.58, 95% CI = 0.42-0.79). The similar results were obtained when stratified by
      gender and age at tumor diagnosis (< or =45 or >45 years). The association
      between MMP-3 -1171 5A/6A or MMP-9 -1562 C/T SNPs and susceptibility to
      astrocytoma was not observed in this study. However, MMP-1 1G-MMP-3 6A haplotype
      significantly reduced the risk of astrocytoma development when using MMP-1 2G-MMP
      3 6A haplotype as a reference (OR = 0.45, 95% CI = 0.29-0.67). The present study
      suggested that, the MMP-1 -1607 1G/1G genotype and MMP-1 1G-MMP-3 6A haplotype
      may play protective role in the development of adult astrocytoma in northern
      Chinese, whereas the MMP-3 -1171 5A/6A and MMP-9 -1562 C/T polymorphisms may not
      be independent factors to influence susceptibility to adult astrocytoma in this
      population.

PMID- 17502999
TI  - Immunological memory of mountain birches: effects of phenolics on performance of
      the autumnal moth depend on herbivory history of trees.
AB  - Plants have been suggested to have an immunological memory comparable to animals.
      The evidence for this, however, is scarce. In our study with the mountain birch -
      Epirrita autumnata system, we demonstrated that birches exposed as long as 5 yr
      to feeding of E. autumnata larvae (delayed induced resistance, DIR), responded
      more strongly to a new challenge than trees without an herbivory history. Pupal
      weights remained lower, and the duration of the larval period was prolonged in
      the DIR trees, although immunity, measured as an encapsulation rate, was not
      affected. We further demonstrated that the effects of birch phenolics on
      performance of E. autumnata were different in the exposed (DIR) trees from naive
      control trees, although we found only one significant change in chemistry. The
      quercetin:kaemferol ratio was increased in DIR trees, suggesting that herbivory
      caused oxidative stress in birches. In DIR trees, phenolics, especially
      hydrolyzable tannins (HTs), affected pupal weights negatively, whereas in control
      trees, the effects were either nonsignificant or positive. HTs also prolonged the
      duration of the larval period of females, whereas peroxidase (POD) activity
      prolonged that of males. We suggest that the causal explanation for the induced
      resistance was an enhanced oxidation of phenolic compounds from the DIR trees in
      the larval digestive tract. Phenolic oxidation produces semiquinones, quinones,
      free radicals, and ROS, which may have toxic, antinutritive, and/or repellent
      properties against herbivores.

PMID- 17503000
TI  - Copper foreign body in the lens without damage of iris and lens capsule.
AB  - PURPOSE: The objective is to report a rare case of asymptomatic penetrating
      injury with a copper foreign body found during an examination for cataract
      surgery. METHOD: A case report. RESULTS: A 73-year-old woman had vision loss.
      Examination by pupil dilation disclosed a dark-brown metallic mass located under
      the anterior capsule of the lens, as well as nuclear sclerosis of the lens.
      Although no history of traumatic injury was reported by the patient, careful
      examination revealed a dot corneal opacity. This finding, and the past history of
      the patient that she had worked in the fabrication of copper wire, suggested
      previous penetrating injury. The iris had no scar. No inflammatory reaction was
      observed in the posterior segment of the eye. Phacoemulsification and
      implantation of an intraocular lens were performed. After continuous curvilinear
      capsulorrhexis (CCC), the foreign body was extracted with a microforceps. The
      anterior capsule overlying the foreign body was intact, with normal light reflex.
      Qualitative analysis showed that the foreign body extracted contained pure copper
      at the center. Nevertheless, visual acuity of the right eye improved from 20/50
      to 20/20 without any copper-related retinal damage. CONCLUSION: In this case,
      copper localized under the anterior capsule of the lens had been able to stay in
      the eye without causing severe inflammatory reaction.

PMID- 17503001
TI  - Microbial production of 1,3-propanediol from glycerol by Klebsiella pneumoniae
      under micro-aerobic conditions up to a pilot scale.
AB  - 1,3-Propanediol (1,3-PD) can be produced from glycerol by Klebsiella pneumoniae
      under micro-aerobic conditions. Recently, this fed-batch fermentation process has
      been successfully scaled up to 1 m(3). The final 1,3-PD concentration, molar
      yield and volumetric productivity of 72 g l(-1), 57% and 2.1 g l(-1 )h(-1),
      respectively, are close to those of 75 g l(-1), 61%, and 2.2 g l(-1 )h(-1) under
      anaerobic conditions. This process would be suitable for the production of 1,3-PD
      on a large scale.

PMID- 17503002
TI  - Carbon dioxide fixation by Chlorella kessleri, C. vulgaris, Scenedesmus obliquus
      and Spirulina sp. cultivated in flasks and vertical tubular photobioreactors.
AB  - CO(2) at different concentrations were added to cultures of the eukaryotic
      microalgae, Chlorella kessleri, C. vulgaris and Scenedesmus obliquus, and the
      prokaryotic cyanobacterium, Spirulina sp., growing in flasks and in a
      photobioreactor. In each case, the best kinetics and carbon fixation rate were
      with a vertical tubular photobioreactor. Overall, Spirulina sp. had the highest
      rates. Spirulina sp., Sc. obliquus and C. vulgaris could grow with up to 18%
      CO(2).

PMID- 17503003
TI  - Use of an industrial grade medium and medium enhancing effects on high cell
      density CO fermentation by Eubacterium limosum KIST612.
AB  - Studies were made on the composition of the growth medium to increase the cell
      concentration in a cell-recycled continuous culture (Eubacterium limosum KIST612)
      with carbon monoxide as a sole energy source using phosphate-buffered basal
      medium (PBBM) and modified PBBM. One of major limiting factors in PBBM might be
      nitrogen during the high cell density culture. This limitation could be overcome
      by increasing of inorganic nitrogen or yeast extract concentration in the medium.
      Anaerobic digester fluid, which could replace the organic nitrogen in PBBM, was
      used to develop an industrial grade medium for conversion of CO to multi-carbon
      compound.

PMID- 17503004
TI  - Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation,
      insulin resistance, and body weight in developing obese Zucker rats.
AB  - Super CitriMax (HCA-SX) is a novel calcium/potassium salt of (-)-hydroxycitric
      acid extracted from the dried fruit rind of the plant Garcinia cambogia, and
      commonly consumed as weight loss dietary supplement. In the present study, we
      investigated the effect of HCA-SX on inflammation, oxidative stress and insulin
      resistance in developing obese Zucker rats, an animal model of type II diabetes
      associated with inflammation and oxidative stress. Male Zucker rats (5-week old)
      were supplemented with vehicle (control) and HCA-SX in drinking water for 7
      weeks. Oxidative stress markers, including malondialdehyde (MDA), protein
      carbonyl (DNPH), and protein tyrosine nitration (tyr-NO(2)) were measured in the
      liver and kidney tissues using biochemical and immunoblotting techniques.
      Compared to controls, the levels of MDA, DNPH and tyr-NO(2) were lower in the
      liver and kidney of HCA-SX-treated animals. Furthermore, the levels of C-reactive
      protein and interleukin-6, markers of inflammation measured by ELISA, were lower
      in the plasma of HCA-SX-supplemented animals compared to controls, as were levels
      of fasting plasma insulin, glucose, and triglycerides. Interestingly, insulin
      resistance did not develop in HCA-SX-supplemented rats. Food-intake and body
      weight gain was also lower in rats supplemented with HCA-SX compared to their
      control counterparts. These results suggest that HCA-SX supplementation in obese
      Zucker rats reduces food-intake, body weight gain, and also attenuates the
      increases in inflammation, oxidative stress, and insulin resistance observed in
      untreated animals. Therefore, HCA-SX may be used as an intervention to overcome
      obesity-related complications, including inflammation, oxidative stress, and
      insulin resistance.

PMID- 17503005
TI  - Arrest of transcription following anoxic exposure in a marine mollusc.
AB  - The intertidal marine snail, Littorina littorea, is an anoxia tolerant species
      that endures long-term oxygen deprivation using a suite of compensatory metabolic
      adaptations that includes overall metabolic rate depression. Nuclear run-off
      assays were used to quantify the relative rates of mRNA transcription in nuclear
      extracts from hepatopancreas of aerobic and anoxic snails. Total [(32)P]-UTP
      incorporation into RNA by nuclei from 48 h anoxic snails ranged from 42 to 50% of
      that observed for nuclei from normoxic snails. When this data is transformed with
      respect to incubation time, the rate of [(32)P]-UTP incorporation by nuclei from
      48 h anoxic snails showed a decrease of 68% as compared with the normoxic level.
      Examination of selected expressed sequence tags also showed an overall decrease
      in mRNA transcription levels in samples derived from anoxic nuclei as compared
      with normoxic nuclei. Control of ribosomal translation was also examined by
      assessing the levels of the eukaryotic initiation factors eIF-2alpha and eIF-4E
      and the eukaryotic elongation factor-1gamma (eEF-1gamma). Levels of eIF-4E and
      eEF-1gamma did not change between aerobic and anoxic states, but the amount of
      phosphorylated inactive eIF-2alpha rose strongly under anoxic conditions
      indicating that control of this factor is key to suppressing protein translation
      in anoxic snails. Since gene transcription is an ATP expensive process in cells,
      suppression of transcription to minimum levels provides substantial energy
      savings for the hepatopancreas, and the organism as a whole, under anoxic
      conditions.

PMID- 17503007
TI  - Birthweight by gestational age and childhood cancer.
AB  - The objective of this research was to compare the association of birthweight
      alone with gender-specific birthweight-for-gestational age on childhood cancer
      risk in a large population-based case-control study in Germany. Incident cases of
      childhood cancer (n=2,024, diagnosed 1992-1994) were ascertained from the German
      Childhood Cancer Registry. Controls were randomly drawn from population
      registries. Parents reported risk factor information in a mailed questionnaire
      and telephone interview. The odds ratio for acute lymphoblastic leukemia (ALL)
      was 1.41 (95% confidence interval 1.08-1.84) in the high-birthweight category (>4
      kg) and was 1.45 (1.07-1.97) in the large-for-gestational age (LGA) category
      compared to the normal birthweight (2.5-4 kg) and the appropriate-for-gestational
      age (AGA) categories, respectively. However, the agreement between the
      birthweight and birthweight-for-gestational age was only moderate. Subgroup
      analyses revealed elevated odds ratios for ALL and CNS tumors in first born's who
      were LGA but of normal birth weight. Thus, two findings from this post-hoc
      analysis are worthy of note: (1) the use of birthweight-for-gestation age
      categories within birthweight sub-groups potentially identified new high-risk
      groups among firstborns for ALL tumors and among all children for CNS tumors; and
      (2) although the magnitudes of risk estimators for ALL were comparable in the
      traditional high-birthweight group and in the LGA, the same children were not
      jointly classified in the same newborn categories indicating two potentially
      different subsets of children at risk.

PMID- 17503006
TI  - Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and
      the risk of primary hepatocellular carcinoma (HCC) in a Chinese population.
AB  - OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR), which is expressed in
      the liver, may be involved in both DNA methylation and DNA synthesis. It is also
      indicated as a potential risk factor of liver cancer in patients with chronic
      liver disease. To date, no study has been conducted on MTHFR and hepatocellular
      carcinoma (HCC) using a population-based design. The objective of this study was
      to evaluate the effects of polymorphisms of the MTHFR gene on the risk of primary
      liver cancer and their possible effect modifications on various environmental
      risk factors. METHODS: A population-based case-control study was conducted in
      Taixing, China. MTHFR C677T and A1298C were assayed by PCR-RFLP techniques.
      RESULTS: The frequency of MTHFR 677 C/C wild homozygotes genotype was 25.8% in
      cases, which was lower than that in controls (34.5%). The adjusted odds ratios
      (ORs) for the MTHFR 677 C/T and T/T genotype were 1.66(95% CI: 1.06-2.61),
      1.21(95% CI: 0.65-2.28) respectively when compared with the MTHFR 677 C/C
      genotype. Subjects carrying any T genotype have the increased risk of 1.55(95%
      CI: 1.01-2.40) for development of primary hepatocellular carcinoma. A high degree
      of linkage disequilibrium was observed between the C677T and A1298C
      polymorphisms, with the D' of 0.887 and p < 0.01. The MTHFR 677 any T genotype
      was suggested to have potentially more than multiplicative interactions with raw
      water drinking with p-value for adjusted interaction of 0.03. CONCLUSION: We
      observed that the MTHFR 677 C/T genotype was associated with an increased risk of
      primary liver cancer in a Chinese population. The polymorphism of MTHFR 677 might
      modify the effects of raw water drinking on the risk of primary hepatocellular
      carcinoma.

PMID- 17503008
TI  - [Phonovibrogram: vocal fold dynamics integrated within a single image].
AB  - BACKGROUND: Stroboscopy is widely used and is quite adequate for the examination
      of normal voices, but with increasing hoarseness its suitability declines, even
      when it is supplemented by video recordings and image evaluation. Real-time
      procedures such as videokymography or high-speed (HS) video imaging are more
      suitable methods of observing the movements of the vocal folds in such cases. A
      drawback of any video recording is the later time-consuming offline replay of the
      films in slow motion and our restricted pattern recognition for motion and other
      time-dependent processes. METHODS: The phonovibrogram (PVG) is an image
      processing algorithm that extracts the vocal fold motions of a whole
      laryngoscopic HS video film and automatically compresses them into a single
      image. RESULTS: Simple patterns that vary from person to person are revealed by
      PVG; these can be categorized by means of simple geometric forms, which a human
      observer can more easily recognize and interpret than dynamic motion patterns.
      The PVG computation is described in detail and an extensive guide to
      interpretation is given, illustrated by reference to theoretical and real
      examples. CONCLUSION: In clinical conditions, HS laryngoscopic video recording is
      useful only in association with automatic image processing. The PVG procedure is
      a promising approach and tests should be performed with a view to further
      clinical validation.

PMID- 17503009
TI  - [Proximal femoral fractures in the elderly. Data from health insurance providers
      on more than 23 million insured persons--part 2].
AB  - BACKGROUND: The section of geriatric trauma ("AG-Alterstraumatologie") of
      the"Deutsche Gesellschaft fur Unfallchirurgie" (DGU) and the"Lohmann & Birkner
      Health Care Consulting GmbH" in co-operation with the health insurance funds
      (VdAK and AEV) supplied the relevant data of approximately 23 million insured
      persons from the years 2002 to 2004. All data from patients over the age of 60
      staying in hospital because of proximal femur fractures and without further
      injuries as the main diagnosis were extracted from the available amount of data
      and then analysed. RESULTS: In comparison to the effective number of beds there
      was a significant increase in the treatment of proximal femur fractures in
      hospitals with 101-300 beds. There was no difference in the operative treatment
      of proximal femur fractures in comparison to the number of beds of the hospital.
      The average hospital expense for osteosynthesis was 6000 euro per each case and
      there was no difference in comparison to the different osteosynthetic procedures.
      The average hospital expense for hip replacement (7036-7201 euro) was about 1000
      euro higher than osteosynthetic procedures. There was no difference in the
      average hospital expense in comparison to the age of the patients. CONCLUSION:
      There was a significant age-dependent increase of acute hospital mortality with a
      maximum of 8.6% in the group of the patients older than 85 years. As a result of
      the demographic change fracture rates in the elderly population will rise
      significantly.

PMID- 17503010
TI  - [Proximal femoral fractures in the elderly. Analysis of data from health
      insurance providers on more than 23 million insured persons--part 1].
AB  - BACKGROUND: The section of geriatric trauma ("AG-Alterstraumatologie") of the
      "Deutsche Gesellschaft fur Unfallchirurgie" (DGU) and the "Lohmann & Birkner
      Health Care Consulting GmbH" in co-operation with the health insurance funds
      (VdAK and AEV) supplied the relevant data of approximately 23 million insured
      persons from the years 2002 to 2004. METHODS: All data from patients over the age
      of 60 staying in hospital because of proximal femur fractures and without further
      injuries as the main diagnosis were extracted from the available amount of data
      and then analysed. There were 68,929 (9.5%) cases diagnosed with proximal femur
      fractures of 724,606 patients treated in hospital. RESULTS: There was a
      significant age-dependent increase in incidents of proximal femur fractures with
      a maximum of 3,000 injuries around the age of 82 years. The surgical treatment of
      proximal femur fractures was carried out with a joint-preserving stabilising
      method (osteosynthesis-screws-"DHS"-nailing systems) in 49.5%, with
      endoprosthesis in 48.6 % as well as other methods in 1.9% of the cases. In
      comparison to hip replacement care, a shorter hospital stay could be proved with
      osteosynthetic methods.

PMID- 17503011
TI  - [Diagnosis of sylvian and perisylvian epilepsies. Excitation symptomes of the
      insula reilii].
AB  - The insula is a hidden part in the cerebral cortex about which relatively little
      neurological research has been done. The present manuscript describes
      architectural and evolutionary aspects of the insula reilii as well as its
      function, towards a better understanding of seizure semiology. As the literature
      of such casuistry is poor, some own cases are presented. Seizure semiology,
      imaging, magnetoencephalographic reports, resective epilepsy surgery,
      radiosurgical treatments, and thermolesions are described. Magnetic source
      imaging as noninvasive treatment can deliver important information for the
      involvement of sylvian and perisylvian regions in focal pharmacoresistant
      epilepsies.

PMID- 17503012
TI  - Data resolution: a jackknife procedure for determining the consistency of
      molecular marker datasets.
AB  - The results of genetic diversity studies using molecular markers not only depend
      on the biology of the studied objects but also on the quality of the marker data.
      Poor data quality may hamper the correct answering of biological questions. A new
      statistic is proposed to estimate the quality of a marker data set with regard to
      its ability to describe the structure of the biological material under study.
      This statistic is called data resolution (DR). It is calculated by splitting a
      marker data set at random into two sets each with half the number of markers. In
      each set, similarities between all pairs of objects are calculated. Subsequently,
      the similarities obtained for the two sets are correlated. This process is
      repeated a large number of times. The average of the correlation coefficients
      obtained in this way is the DR of the dataset. In the present paper, the DR
      statistic is applied to four studies involving amplified fragment length
      polymorphism as well as micro-satellite markers. In addition, some properties and
      possible applications of DR are discussed, including the prediction of the added
      value of scoring additional markers, and the determination of which similarity
      measure is, apart from genetical considerations, most appropriate for analyzing
      the data.

PMID- 17503013
TI  - Development of an integrated intraspecific map of chickpea (Cicer arietinum L.)
      using two recombinant inbred line populations.
AB  - A composite intraspecific linkage map of chickpea was developed by integrating
      individual maps developed from two F(8:9) RIL populations with one common parent.
      Different molecular markers viz. RAPD, ISSR, RGA, SSR and ASAP were analyzed
      along with three yield related traits: double podding, seeds per pod and seed
      weight. A total of 273 markers and 186 RILs were used to generate the map with
      eight linkage groups at a LOD score of >/=3.0 and maximum recombination fraction
      of 0.4. The map spanned 739.6 cM with 230 markers at an average distance of 3.2
      cM between markers. The predominantly used SSR markers facilitated identification
      of homologous linkage groups from the previously published interspecific linkage
      map of chickpea and confirmed conservation of the SSR markers across the two maps
      as well as the variation in terms of marker distance and order. The double
      podding gene was tagged by the markers NCPGR33 and UBC249z at 2.0 and 1.1 cM,
      respectively. Whereas, seeds per pod, was tagged by the markers TA2x and UBC465
      at 0.1 and 1.8 cM, respectively. Eight QTLs were identified that influence seed
      weight. The joint map approach allowed mapping a large number of markers with a
      moderate coverage of the chickpea genome and few linkage gaps.

PMID- 17503014
TI  - Adenosine for salbutamol-induced supraventricular tachycardia.

PMID- 17503016
TI  - Pseudomonas aeruginosa carriage, colonization, and infection in ICU patients.
AB  - OBJECTIVE: We evaluated whether Pseudomonas aeruginosa associated nosocomial
      infections in our ICU originate mainly from patients' endogenous flora or from
      exogenous cross-transmission. DESIGN AND SETTING: A 6-month prospective
      surveillance survey was performed according to standardized protocols at the
      interdisciplinary ICU of the Azienda Ospedaliera Cannizzaro. PATIENTS: The study
      analyzed 121 patients and focused on three different states: carriage upon
      admission, colonization of sterile sites, and infections during ICU stay.
      RESULTS: We identified 138 P. aeruginosa isolates from 45 patients. The
      cumulative incidence of P. aeruginosa sustained colonization in the ICU was
      29.9/100 patients, and the incidence density was 16.2/1,000 patient-days. The
      cumulative incidence of P. aeruginosa-sustained infections in the ICU was
      36.7/100 patients, and the incidence density was 19.9/1,000 patient-days. The
      most frequent infection type was ventilator-associated pneumonia. PFGE analysis
      of P. aeruginosa isolates led to the identification of a major clone represented
      by 60.8% of isolates involving 45.9% of patients. The impact of cross
      transmission, i.e., the preventable proportion of P. aeruginosa acquisition, was
      estimated to be at least 59.5% of all colonization or infection episodes.
      Acquisition of multidrug-resistant P. aeruginosa was significantly associated
      with cross-transmission. CONCLUSIONS: Our results suggest that the ICU personnel
      and environment served as reservoirs for cross-transmission and emphasize the
      importance of exogenous acquisition of multidrug-resistant P. aeruginosa, of
      reduction in antibiotic pressure, and prompt enforcement of infection control
      measures.

PMID- 17503015
TI  - Invasive candidiasis in pediatric intensive care patients: epidemiology, risk
      factors, management, and outcome.
AB  - BACKGROUND: The incidence of candidemia in pediatric patients follows the same
      pattern of increase as in adults, but the rate of increase is greater. Pediatric
      patients in critical condition, particularly young infants, are especially
      vulnerable to invasive Candida infections (ICI), partly because of their age and
      severe underlying disease and partly because of the invasive procedures used.
      DISCUSSION: Central venous catheters and arterial lines, parenteral nutrition,
      mechanical ventilation and extended use of antimicrobials enhance the risk of
      ICI. C. albicans continues to be the most prevalent isolate. However, an
      increasing role of non-C. albicans (NAC) spp., some of which are intrinsically or
      potentially resistant to antifungal agents, has been observed. NAC spp.,
      particularly C. parapsilosis and C. tropicalis, account for almost half of ICI.
      The increased use of antifungals in immunocompromised patients, mainly
      prophylactically, is considered the strongest contributory factor to the changes
      in species distribution, which have subsequently affected the mortality and
      choice of empirical treatment. CONCLUSIONS: Prompt removal of lines and
      initiation of antifungal treatment are the milestones of management. Conventional
      amphotericin B remains a commonly used antifungal agent, but its lipid
      formulations and fluconazole are also used frequently. Novel antifungal agents
      such as second-generation triazoles and echinocandins exhibit potential as
      alternative agents in critically ill children with ICI. Although response rates
      are still far from satisfactory, improved understanding of risk factors,
      preventive strategies and new treatment options promise a better future outcome.

PMID- 17503017
TI  - Detection of Neisseria meningitidis DNA from skin lesion biopsy using real-time
      PCR: usefulness in the aetiological diagnosis of purpura fulminans.
AB  - OBJECTIVE: The present study evaluated the usefulness of a real-time polymerase
      chain reaction (rtPCR) assay for the detection of Neisseria meningitidis (Nm) and
      genogrouping on skin lesion biopsies in patients with purpura fulminans (PF).
      DESIGN: Retrospective single-centre study. SETTING: Adult and paediatric
      intensive care units at the University Hospital of Rouen. PATIENTS: All patients
      admitted between January 2000 and January 2006, with a final diagnosis of PF and
      for which a skin biopsy and blood cultures were performed, were included.
      INTERVENTIONS: Skin biopsy and blood cultures were used for culture and rtPCR.
      MEASUREMENTS AND MAIN RESULTS: Thirty-four patients fulfilled the criteria (27
      children and 7 adults). Nm rtPCR performed on skin biopsy was positive in 100%
      (34/34) of cases, compared with only 14.7% (5/34) for skin culture (p=0.0001).
      rtPCR genogrouping on skin biopsy was positive in 58.8% (20/34) of the cases
      compared with 14.7% (5/34) for skin culture (p=0.0013). For patients (n=17) in
      whom rtPCR was performed both on blood and skin biopsy, skin biopsy gave a
      significantly higher rate of Nm detection [100% (17/17) vs. 58.8% (10/17);
      p=0.023] and genogroup characterisation [76.5% (13/17) vs. 35.3% (6/17); p=0.045]
      than blood. We encountered no specimen with culture-positive and rtPCR-negative
      results (negative predictive value of rtPCR 100%). CONCLUSION: In suspected PF
      cases, skin biopsy is more reliable to identify Nm and its genogroup than blood
      or, probably, CSF, especially when PCR methods are used. This could help the
      implementation of public health interventions, especially concerning a
      vaccination policy.

PMID- 17503018
TI  - Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation
      injury and septic shock.
AB  - OBJECTIVE: To investigate ceftazidime in acute lung injury (ALI) and sepsis.
      DESIGN AND SETTING: Prospective, randomized, controlled animal study in an
      investigational ICU at a university hospital. INTERVENTIONS: Eighteen female
      Merino sheep were prepared for chronic study and subjected to smoke inhalation
      and septic challenge according to an established protocol. MEASUREMENTS AND
      RESULTS: Whereas global hemodynamics and oxygenation remained stable in sham
      animals (no injury, no treatment), the injury contributed to a hypotensive
      hyperdynamic circulation in the control group (smoke inhalation and sepsis, no
      treatment), as indicated by a significant increase in cardiac index) and heart
      rate and a drop in mean arterial pressure. Treatment with ceftazidime (smoke
      inhalation and sepsis, treatment group) stabilized cardiac index and heart rate
      and attenuated the decrease in mean arterial pressure. The deterioration in
      PaO2/FiO2 ratio and pulmonary shunt fraction (Qs/Qt) was significantly delayed
      and blunted by ceftazidime. At 24 h after injury a significant increase in airway
      obstruction scores of bronchi and bronchioles in both injured groups was
      observed. Ceftazidime significantly reduced airway obstruction vs. control
      animals. Whereas plasma nitrate/nitrite levels increased similarly in the two
      injured groups, lung 3-nitrotyrosine content remained at the baseline level in
      the ceftazidime group. CONCLUSIONS: In ovine lung injury ceftazidime improves
      global hemodynamics and oxygenation not only by bacterial clearance but also via
      reduction in toxic nitrogen species such as 3-nitrotyrosine. Therefore
      ceftazidime appears as a clinically relevant adjunct in the common setting of
      sepsis-associated lung injury.

PMID- 17503019
TI  - The mid- to long-term results of the anterior cruciate ligament reconstruction
      with hamstring tendons using Transfix technique.
AB  - In this study, mid to long-term results of anterior cruciate ligament
      reconstruction with hamstring tendons and Transfix technique were evaluated.
      Anterior cruciate ligament (ACL) reconstruction with four-strand hamstring tendon
      was performed with Transfix technique on 271 (198 males, 73 females; mean age
      25.7; 17-52) patients with anterior cruciate ligament ruptures. The patients were
      followed up with clinical examination, Lysholm and Tegner activity scales, IKDC
      scoring system, KT-1000 test and radiological examination. The mean follow-up
      period was 82 (48-100) months; 204 (75%) patients had no subjective complaints.
      According to the KT-1000 test, only 14 (5%) patients had more than 5 mm laxity
      postoperatively, whereas, 161 (59%) patients had more than 5 mm laxity
      preoperatively. In addition to this, only 19 (7%) patients had Lysholm scores
      less than 80 postoperatively, whereas 154 (57%) patients scored less than 80
      preoperatively. When compared with Tegner activity scale, 189 (70%) patients
      scored<6 preoperatively and only 24 (8%) postoperatively; 78 (29%) patients
      scored D preoperatively and only 5 (2%) patients scored D postoperatively on the
      basis of the IKDC scoring system. Our functional results were found to be
      satisfactory in more than 90% of patients. Commonly seen problems in ACL
      reconstruction such as inaccurate graft placement and tunnel widening were found
      to be consistent with the values in relevant literature. However, we demonstrated
      that the functional results and the stability of the knee were not related with
      tunnel widening. This study concludes that the reconstruction of ACL with
      hamstring tendons and the Transfix technique is reasonably successful, safe and
      causes low morbidity. Furthermore, we believe that proper graft preparation,
      accurate tunnel placement, notch-plasty, fixation and rehabilitation program are
      all as important as the choice of graft and fixation material.

PMID- 17503020
TI  - Isozyme- and gender-specific induction of glutathione S-transferases by
      flavonoids.
AB  - Most dietary flavonoids have antioxidant activity in vitro however, secondary
      mechanisms such as the ability to influence gene expression with the consequent
      modulation of specific enzymatic activities involved in the intracellular
      response against oxidative stress, are being realized. In the following study, we
      examined the ability of the flavonoids: flavone, morin, naringenin, (+)-catechin,
      and quercetin to modulate the activity of glutathione S-transferases (GSTs)
      mGSTA, mGSTP and mGSTM in hepatic tissues of male and female Swiss Webster mice.
      Subchronic dietary exposure to morin, naringenin, (+)-catechin, and quercetin
      (2,500 mg/kg diet for 20 days) did not produce statistically significant changes
      in GST activity. Conversely, gender-, and isozyme-specific induction of mGSTs
      were observed in animals fed flavone. A sevenfold increase in total mGST activity
      was observed in female animals whereas a fourfold increase was observed in male
      animals. Enzyme specific assays indicate that there were greater increases of
      both mGSTM (eightfold) and mGSTP (fourfold) activities in females as compared to
      males (sixfold and twofold, respectively). As testosterone is involved in the
      regulation of GSTs in mice, castrated males were fed flavone for 5 days (2,500
      mg/kg diet). In this case, dietary flavone resulted in similar fourfold increases
      in total GST activity in inact and castrated animals. Isozyme specific studies
      indicate that increases could be attributed to an induction of mGSTM and mGSTP.

PMID- 17503021
TI  - Analysis of cell death inducing compounds.
AB  - Biomarkers for early detection of toxicity hold the promise of improving the
      failure rates in drug development. In the present study, gene expression levels
      were measured using full-genome RAE230 version 2 Affymetrix GeneChips on rat
      liver tissue 48 h after administration of six different compounds, three toxins
      (ANIT, DMN and NMF) and three non-toxins (Caeruelein, Dinitrophenol and
      Rosiglitazone). We identified three gene transcripts with exceptional predictive
      performance towards liver toxicity and/or changes in histopathology. The three
      genes were: glucokinase regulatory protein (GCKR), ornithine aminotransferase
      (OAT) and Cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase) (Cyp2C29).
      RT-PCR for these three genes was performed and four additional compounds were
      included for validation. The quantitative RT-PCR analysis confirmed the findings
      based on the microarray data and using the three genes a classification rate of
      55 of 57 samples was achieved for the classification of not toxic versus toxic.
      The single most promising biomarker (OAT) alone resulted in a surprisingly 100%
      correctly classified samples. OAT has not previously been linked to toxicity and
      cell death in the literature and the novel finding represents a putative
      hepatotoxicity biomarker.

PMID- 17503023
TI  - Molecular recognition of polycyclic aromatic hydrocarbons by pyrene-imprinted
      microspheres.
AB  - Pyrene-imprinted microbeads that display molecular recognition towards
      polyaromatic hydrocarbons (PAHs) were obtained by the aqueous suspension
      thermopolymerization of a mixture of template, 4-vinylpyridine and divinylbenzene
      in the molar ratio of 1:8:40. The microbeads were packed into an HPLC column and
      the retention behaviour of pyrene in the presence of eluents of increasing
      polarity was investigated by measuring the binding capacity and the imprinting
      factor. Selectivity was evaluated by eluting pyrene and 22 other related PAHs in
      the HPLC column when equilibrated with acetonitrile-dichloromethane 4:1 (v/v).
      Twelve molecular descriptors were calculated for each PAH molecule: MW, the
      molecular weight; SAS, the solvent-accessible molecular surface area; Svdw, the
      van der Waals molecular surface area; Vol, the van der Waals molecular volume;
      MOv, the molecular ovality; RG, the radius of gyration; B/L, the breadth-to
      length ratio; micro(2), the square of the total dipole moment; HOMO, the highest
      occupied molecular orbital; LUMO, the lowest unoccupied molecular orbital;
      Deltaorb, the absolute value of the difference between the HOMO and LUMO; log P,
      the logarithm of the n-octanol-water partition coefficient. Quantitative
      structure-retention relationships between the logarithm of the capacity factors
      and these descriptors were searched for using a multiple linear regression (MLR)
      method. The best regression models obtained showed that the capacity factor
      correlated well with those molecular descriptors which had structural character,
      such as logP, while the effect of the molecular descriptors with electronic
      character was negligible. The results obtained indicate that the molecular
      recognition of PAHs by the imprinted polymer is controlled by the shape and
      dimension of the binding sites through hydrophobic interactions.

PMID- 17503024
TI  - Amplification of noble gas ion lines in the afterglow of a pulsed hollow cathode
      discharge and possible benefit for analytical glow discharge mass spectrometry.
AB  - A high-current pulsed hollow cathode discharge was used to study the role of
      atomic and ionic metastables involved in ionization plasma processes. We observed
      the enhancement of the spectral emission lines of noble gas ions in the
      afterglow. A study of the processes that involve atomic and ionic metastables is
      of great interest since it should lead to a better understanding of and enhanced
      control over the ionization mechanisms crucial to analytical glow discharge mass
      spectrometry (GDMS) analysis.

PMID- 17503025
TI  - Effects of visual uncertainty on grasping movements.
AB  - To successfully lift an object, a person's fingers must be moved to locations
      where forces can be applied that are sufficient for maintaining contact and that
      allow for easy object manipulation. Obtaining such finger positions becomes more
      difficult when there is perceptual uncertainty about the location of the hand and
      object. However, knowledge about the amount of uncertainty could be incorporated
      into grasp plans to mitigate its effect. For example, during peripheral viewing
      the fingers could open wider to avoid colliding with or missing the object. The
      goal of this study is to determine the degree to which people incorporate their
      understanding of visual uncertainty when making a precision grasp. To
      investigate, subjects reached to a spatially fixed object whose retinal location
      was varied by fixating points 0-80 degrees to the left of the object. This
      manipulation controlled the visual uncertainty of the hand and target without
      affecting the kinematic demands of the task. We found that people systematically
      changed their grasping behavior as a function of the amount of visual uncertainty
      in the task. Specifically, subjects' maximum grip aperture increased linearly
      with target eccentricity. Moreover, the effect of visual uncertainty on finger
      trajectories could be captured by a single dimension of change along an axis.
      Together, these findings suggest that the sensorimotor system estimates visual
      uncertainty and behaviorally adjusts for it during grasping movements.

PMID- 17503026
TI  - Concentration-detection functions for eye irritation evoked by homologous n
      alcohols and acetates approaching a cut-off point.
AB  - We measured the concentration-detection (i.e., psychometric) functions for the
      eye irritation evoked by three homologous n-alcohols (1-nonanol, 1-decanol and 1
      undecanol) and two homologous acetates (nonyl and decyl acetate). A vapor
      delivery device based on a dynamic dilution of stimuli in nitrogen served to
      present various concentrations of each compound, including the undiluted vapor,
      to the subjects (n >or= 26). Delivered concentrations were quantified by gas
      chromatography. Detection probability (P) was assessed via a three-alternative,
      forced-choice procedure and quantified on a scale ranging from P = 0.0 (chance
      detection) to P = 1.0 (perfect detection). Flow rate to the eye equaled 2.5 l/min
      and time of exposure was 6 s. The functions for 1-undecanol and decyl acetate
      plateaued at P approximately 0.5 and P approximately 0.25, respectively, such
      that further increases in concentration failed to increase detection notably.
      Thus, both series reached a break point, or cut-off, in the detection of ocular
      irritation. The present outcome provides additional evidence that the cut-off
      does not rest on the low vapor concentration of the homolog but, more likely, on
      the homolog exceeding a critical molecular dimension(s), which prevents it from
      interacting effectively with the appropriate receptors.

PMID- 17503027
TI  - A new measure for quantifying the bilateral coordination of human gait: effects
      of aging and Parkinson's disease.
AB  - The bilateral coordination of locomotion has been described in detail in animal
      studies and to some degree in man; however, the mechanisms that contribute to the
      bilateral coordination of gait in humans are not fully understood. The objective
      of the present study was to develop a measure for quantifying the bilateral
      coordination of gait and to evaluate the effects of aging and Parkinson's disease
      (PD) on this new metric. To this end, we compared the gait of healthy older
      adults to that of healthy young adults and patients with PD. Specifically, we
      defined the stride duration of one foot as a gait cycle or 360 degrees ,
      determined the relative timing of contra-lateral heel-strikes, and defined this
      as the phase, varphi (ideally, varphi = 180 degrees for every step). The sum of
      the coefficient of variation of varphi and the mean absolute difference between
      varphi and 180 degrees was defined as the phase coordination index (PCI),
      representing variability and inaccuracy, respectively, in phase generation. PCI
      values were higher (poorer bilateral coordination) in patients with PD in
      comparison to the healthy older adults (P < 0.006). Although gait speed and
      stride time variability were similar in the healthy young and older adults, PCI
      values were significantly higher among the healthy elderly subjects compared to
      the young adults (P < 0.001). Regression analysis suggests that only about 40% of
      the variance in the values of PCI can be explained by the combination of gait
      asymmetry (as defined by the differences in each leg's swing times), gait speed
      and stride time variability, pointing to the independent nature of this new
      metric. This study demonstrates that bilateral coordination of gait deteriorates
      with aging, further deteriorates in PD, and is not strongly associated with other
      spatio-temporal features of gait.

PMID- 17503028
TI  - Bowel venous malformation associated with an aneurysm of the portal vein.
AB  - We report the unique association of a rectosigmoid venous malformation and an
      aneurysm of the portal vein in a 7-year-old child. Doppler ultrasonography
      allowed the diagnosis; MRI confirmed the diagnosis and demonstrated the extent of
      the abnormality. The treatment and evolution over a period of 6 years is
      recorded. The relationship between these two entities and treatment is discussed.

PMID- 17503029
TI  - Herlyn-Werner-Wunderlich syndrome: uterus didelphys, blind hemivagina and
      ipsilateral renal agenesis. Sonographic and MR findings in 11 cases.
AB  - BACKGROUND: Uterus didelphys with obstructed hemivagina and ipsilateral renal
      agenesis is a rare entity, sometimes referred to as Herlyn-Werner-Wunderlich
      syndrome (HWW). It usually presents after menarche with progressive pelvic pain,
      sometimes with regular menses, and a palpable mass due to hemihaematocolpos. The
      diagnosis is generally made only if the suspicion of this genitourinary syndrome
      is raised. OBJECTIVE: To highlight the imaging diagnostic clues in this rare
      condition. MATERIALS AND METHODS: We report on 11 adolescents with this
      condition. RESULTS: Sonography mostly allowed the correct diagnosis by showing
      uterovaginal duplication, haematocolpos or haematometrocolpos, and the absence of
      the ipsilateral kidney. MRI provided more detailed information regarding uterine
      morphology, the continuity with each vaginal channel (obstructed and
      nonobstructed), and the bloody nature of the contents. CONCLUSION: Early and
      accurate diagnosis of this syndrome is important so that adequate and prompt
      surgical therapy (excision of the vaginal septum) can provide relief of pain and
      prevent further complications. It is also advisable to look for an obstructed
      Mullerian system whenever a multicystic dysplastic kidney or the absence of a
      kidney is discovered in a fetus, or girl postnatally.

PMID- 17503030
TI  - MR imaging of isolated left ventricular apical hypoplasia.
AB  - We report the MRI findings in a 3-month-old boy with isolated left ventricular
      apical hypoplasia. This is a recently described congenital abnormality that
      consists of an odd, spherically shaped left ventricle due to absence of the
      ventricular apex. To our knowledge, isolated left ventricular apical hypoplasia
      has not been reported in a child.

PMID- 17503031
TI  - MRI findings of rhabdomyolysis from streptococcal pharyngitis.
AB  - Rhabdomyolysis has been described as a rare sequela of severe infections by group
      A streptococcus related to toxic shock syndrome in adults. Streptococcal
      pharyngitis, on the other hand, has never been reported to cause rhabdomyolysis.
      We report a case of rhabdomyolysis in a child after an uncomplicated course of
      group A streptococcal pharyngitis. Although MRI of rhabdomyolysis from other
      causes has been described in a few case reports, this is a unique MRI description
      of its occurrence with streptococcal pharyngitis.

PMID- 17503032
TI  - Organisation of nucleosomal arrays reconstituted with repetitive African green
      monkey alpha-satellite DNA as analysed by atomic force microscopy.
AB  - Alpha-satellite DNA (AS) is part of centromeric DNA and could be relevant for
      centromeric chromatin structure: its repetitive character may generate a
      specifically ordered nucleosomal arrangement and thereby facilitate kinetochore
      protein binding and chromatin condensation. Although nucleosomal positioning on
      some satellite sequences had been shown, including AS from African green monkey
      (AGM), the sequence-dependent nucleosomal organisation of repetitive AS of this
      species has so far not been analysed. We therefore studied the positioning of
      reconstituted nucleosomes on AGM AS tandemly repeated DNA. Enzymatic analysis of
      nucleosome arrays formed on an AS heptamer as well as the localisation of
      mononucleosomes on an AS dimer by atomic force microscopy (AFM) showed one major
      positioning frame, in agreement with earlier results. The occupancy of this site
      was in the range of 45-50%, in quite good agreement with published in vivo
      observations. AFM measurements of internucleosomal distances formed on the
      heptamer indicated that the nucleosomal arrangement is governed by sequence
      specific DNA-histone interactions yielding defined internucleosomal distances,
      which, nevertheless, are not compatible with a uniform phasing of the nucleosomes
      with the AGM AS repeats.

PMID- 17503033
TI  - Expression of glf Z.m. increases D-mannitol formation in whole cell
      biotransformation with resting cells of Corynebacterium glutamicum.
AB  - A recombinant oxidation/reduction cycle for the conversion of D-fructose to D
      mannitol was established in resting cells of Corynebacterium glutamicum. Whole
      cells were used as biocatalysts, supplied with 250 mM sodium formate and 500 mM D
      fructose at pH 6.5. The mannitol dehydrogenase gene (mdh) from Leuconostoc
      pseudomesenteroides was overexpressed in strain C. glutamicum ATCC 13032. To
      ensure sufficient cofactor [nicotinamide adenine dinucleotide (reduced form,
      NADH)] supply, the fdh gene encoding formate dehydrogenase from Mycobacterium
      vaccae N10 was coexpressed. The recombinant C. glutamicum cells produced D
      mannitol at a constant production rate of 0.22 g (g cdw)(-1) h(-1). Expression of
      the glucose/fructose facilitator gene glf from Zymomonas mobilis in C. glutamicum
      led to a 5.5-fold increased productivity of 1.25 g (g cdw)(-1) h(-1), yielding 87
      g l(-1) D-mannitol from 93.7 g l(-1) D-fructose. Determination of intracellular
      NAD(H) concentration during biotransformation showed a constant NAD(H) pool size
      and a NADH/NAD(+) ratio of approximately 1. In repetitive fed-batch
      biotransformation, 285 g l(-1) D-mannitol over a time period of 96 h with an
      average productivity of 1.0 g (g cdw)(-1) h(-1) was formed. These results show
      that C. glutamicum is a favorable biocatalyst for long-term biotransformation
      with resting cells.

PMID- 17503034
TI  - High-efficiency recovery of target cells using improved yeast display system for
      detection of protein-protein interactions.
AB  - We constructed a high-throughput screening (HTS) system for target cells based on
      the detection of protein-protein interactions by flow cytometric sorting due to
      the improvement in the yeast cell surface display system. Interaction model
      proteins, which are the ZZ domain derived from Staphylococcus aureus and the Fc
      part of human immunoglobulin G (IgG), were displayed on the yeast cell surface.
      We achieved a rapid and enhanced expression of these proteins as a result of
      adopting an appropriate yeast strain and a suitable promoter. The displayed ZZ
      domain had an ability to bind to rabbit IgG and the displayed Fc part to protein
      A. These were confirmed by flow cytometry and fluorescence microscopy.
      Furthermore, the cells displaying the ZZ domain or Fc part were isolated from the
      model libraries constructed by mixing the control yeast cells with the target
      yeast cells. The ratio of the target cells was increased from 0.0001% to more
      than 70% by two cycles of cell sorting. These results indicate that we can
      achieve a rapid and highly efficient isolation method for the target cells with
      FACSCalibur and that this method will further extend the application of flow
      cytometric sorting to library selections.

PMID- 17503035
TI  - Biotechnological intensification of biogas production.
AB  - The importance of syntrophic relationships among microorganisms participating in
      biogas formation has been emphasized, and the regulatory role of in situ hydrogen
      production has been recognized. It was assumed that the availability of hydrogen
      may be a limiting factor for hydrogenotrophic methanogens. This hypothesis was
      tested under laboratory and field conditions by adding a mesophilic (Enterobacter
      cloacae) or thermophilic hydrogen-producing (Caldicellulosyruptor
      saccharolyticus) strain to natural biogas-producing consortia. The substrates
      were waste water sludge, dried plant biomass from Jerusalem artichoke, and pig
      manure. In all cases, a significant intensification of biogas production was
      observed. The composition of the generated biogas did not noticeably change. In
      addition to being a good hydrogen producer, C. saccharolyticus has cellulolytic
      activity; hence, it is particularly suitable when cellulose-containing biomass is
      fermented. The process was tested in a 5-m(3) thermophilic biogas digester using
      pig manure slurry as a substrate. Biogas formation increased at least 160-170%
      upon addition of the hydrogen-producing bacteria as compared to the biogas
      production of the spontaneously formed microbial consortium. Using the
      hydrogenase-minus control strain provided evidence that the observed enhancement
      was due to interspecies hydrogen transfer. The on-going presence of C.
      saccharolyticus was demonstrated after several months of semicontinuous
      operation.

PMID- 17503037
TI  - Endometriosis of the superior gluteal nerve.
AB  - Endometriosis that involves nerves is rare and usually occurs in the pelvis. We
      describe a case of extra-pelvic endometriosis that involved the superior gluteal
      nerve. The patient presented with ill-defined buttock and thigh pain and a
      Trendelenberg gait. MRI demonstrated atrophic changes in the gluteus minimus,
      gluteus medius and tensor fascia lata muscles indicating involvement of the
      superior gluteal nerve. MRI showed a mass in the line of the superior gluteal
      nerve. The mass was hyperintense on STIR and T1-weighted images and did not
      enhance after intravenous contrast although surrounding edema did enhance.
      Histological examination of material obtained at open biopsy showed
      endometriosis. The patient was commenced on hormonal treatment to suppress
      ovarian activity.

PMID- 17503038
TI  - Administering radioiodine treatment; alternative to nuclear medicine prescribing.

PMID- 17503039
TI  - Sequential FDG-PET/CT reliably predicts response of locally advanced rectal
      cancer to neo-adjuvant chemo-radiation therapy.
AB  - PURPOSE: Prediction of rectal cancer response to preoperative, neo-adjuvant chemo
      radiation therapy (CRT) provides the opportunity to identify patients in whom a
      major response is expected and who may therefore benefit from alternative
      surgical approaches. Traditional morphological imaging techniques are effective
      in defining tumour extension in the initial diagnostic and staging work-up, but
      perform poorly in distinguishing residual neoplastic tissue from scarring post
      CRT, when restaging the patient before surgery. Fluorine-18 fluorodeoxyglucose
      positron emission tomography (FDG-PET) is a promising tool for monitoring the
      effect of anti-tumour therapy. The aim of this study was to prospectively assess
      the value of sequential FDG-PET scans in predicting the response of locally
      advanced rectal cancer to neo-adjuvant CRT. METHODS: Forty-four consecutive
      patients with locally advanced (cT3-4) primary rectal cancer and four patients
      with pelvic recurrence of rectal cancer were enrolled in this prospective study.
      Treatment consisted of external beam intensified radiotherapy (50 Gy to the
      posterior pelvis, 56 Gy to the tumour), chemotherapy (in most cases PVI 5-FU at
      300 mg/m(2) per day) and, 8-10 weeks later, surgery with curative intent. All
      patients underwent FDG-PET/CT both before CRT and 5-6 weeks after completing CRT.
      One patient died before surgery because of acute myocardial infarction, and was
      therefore excluded from further analysis. Semi-quantitative measurements of FDG
      uptake (SUV(max)), absolute difference (DeltaSUV(max)) and percent SUV(max)
      difference (Response Index, RI) between pre- and post-CRT PET scans were
      considered. Results were correlated with pathological response, assessed both by
      histopathological staging of the surgical specimens (pTNM) and by the tumour
      regression grade (TRG) according to Mandard's criteria (patients with TRG1-2
      being defined as responders and patients with TRG3-5 as non-responders). RESULTS:
      Following neo-adjuvant CRT, of the 45 patients submitted to surgery, 23 (51.1%)
      were classified as responders according to Mandard's criteria (8 TRG1 and 15
      TRG2), while the remaining 22 (48.9%) were non-responders (9 TRG3 and 13 TRG4-5).
      Considering all patients, the mean pre-CRT SUV(max) was 15.6, significantly
      higher than the mean value of 5.4 post CRT (p < 0.001). Nevertheless, when
      stratifying patients according to response to CRT (using Mandard's criteria), the
      mean RI was significantly higher in responders than in non-responders (75.9%
      versus 46.9%,p = 0.0015). Using a 66.2% SUV(max) decrease as the cut-off value
      (identified by ROC analysis) for defining response to therapy, the following
      parameters were obtained: 79.2% specificity, 81.2% sensitivity, 77% positive
      predictive value, 89% negative predictive value and 80% overall accuracy.
      CONCLUSION: The results suggest the potential utility of FDG-PET as a
      complementary diagnostic and prognostic procedure in the assessment of neo
      adjuvant CRT response of locally advanced rectal cancer. DeltaSUV(max) and RI
      seem the best predictors of CRT response.

PMID- 17503040
TI  - Current approaches in dendritic cell generation and future implications for
      cancer immunotherapy.
AB  - The discovery of tumor-associated antigens, which are either selectively or
      preferentially expressed by tumors, together with an improved insight in
      dendritic cell biology illustrating their key function in the immune system, have
      provided a rationale to initiate dendritic cell-based cancer immunotherapy
      trials. Nevertheless, dendritic cell vaccination is in an early stage, as methods
      for preparing tumor antigen presenting dendritic cells and improving their
      immunostimulatory function are continuously being optimized. In addition, recent
      improvements in immunomonitoring have emphasized the need for careful design of
      this part of the trials. Still, valuable proofs-of-principle have been obtained,
      which favor the use of dendritic cells in subsequent, more standardized clinical
      trials. Here, we review the recent developments in clinical DC generation,
      antigen loading methods and immunomonitoring approaches for DC-based trials.

PMID- 17503041
TI  - Intratumoral delivery of vector mediated IL-2 in combination with vaccine results
      in enhanced T cell avidity and anti-tumor activity.
AB  - Systemic IL-2 is currently employed in the therapy of several tumor types, but at
      the price of often severe toxicities. Local vector mediated delivery of IL-2 at
      the tumor site may enhance local effector cell activity while reducing toxicity.
      To examine this, a model using CEA-transgenic mice bearing established CEA
      expressing tumors was employed. The vaccine regimen was a s.c. prime vaccination
      with recombinant vaccinia (rV) expressing transgenes for CEA and a triad of
      costimulatory molecules (TRICOM) followed by i.t. boosting with rF-CEA/TRICOM.
      The addition of intratumoral (i.t.) delivery of IL-2 via a recombinant fowlpox
      (rF) IL-2 vector greatly enhanced anti-tumor activity of a recombinant vaccine,
      resulting in complete tumor regression in 70-80% of mice. The anti-tumor activity
      was shown to be dependent on CD8(+) cells and NK1.1(+). Cellular immune assays
      revealed that the addition of rF-IL-2 to the vaccination therapy enhanced CEA
      specific tetramer(+) cell numbers, cytokine release and CTL lysis of CEA(+)
      targets. Moreover, tumor-bearing mice vaccinated with the CEA/TRICOM displayed an
      antigen cascade, i.e., CD8(+) T cell responses to two other antigens expressed on
      the tumor and not the vaccine: wild-type p53 and endogenous retroviral antigen
      gp70. Mice receiving rF-IL-2 during vaccination demonstrated higher avidity CEA
      specific, as well as higher avidity gp70-specific, CD8(+) T cells when compared
      with mice vaccinated without rF-IL-2. These studies demonstrate for the first
      time that the level and avidity of antigen specific CTL, as well as the
      therapeutic outcome can be improved with the use of i.t. rF-IL-2 with vaccine
      regimens.

PMID- 17503042
TI  - STAT1-dependent and STAT1-independent gene expression in murine immune cells
      following stimulation with interferon-alpha.
AB  - PURPOSE: The precise molecular targets of interferon-alpha (IFN-alpha) therapy of
      melanoma are unknown but likely involve signal transducer and activator of
      transcription 1 (STAT1) signal transduction within host immune effector cells. We
      hypothesized that microarray analysis could be utilized to identify candidate
      molecular targets important for mediating the anti-tumor effect of exogenously
      administered IFN-alpha. EXPERIMENTAL METHODS: To identify the STAT1-dependent
      genes regulated by IFN-alpha, the gene expression profile of splenocytes from
      wild type (WT) and STAT1(-/-) mice was characterized. RESULTS: This analysis
      identified 30 genes that required STAT1 signal transduction for optimal
      expression in response to IFN-alpha (p < 0.001). These genes include granzyme b
      (Gzmb), interferon regulatory factor 7 (Irf7), Fas death domain-associated
      protein (Daxx), and lymphocyte antigen 6 complex, locus C (Ly6c). The expression
      of 20 genes was found to be suppressed in the presence of STAT1 including
      chemokine ligand 2 (Ccl2), Ccl5, and Ccl7. Nineteen genes were significantly
      upregulated in murine splenocytes following treatment with IFN-alpha regardless
      of the presence of STAT1 including CD86, lymphocyte antigen 6 complex, locus A
      (Ly6a), and Tap binding protein (Tapbp). The expression of representative IFN
      responsive genes was confirmed at the transcriptional level by Real Time PCR.
      CONCLUSION: This report is the first to demonstrate that STAT1-mediated signal
      transduction plays a major role in the transcriptional response of murine immune
      cells to IFNalpha.

PMID- 17503043
TI  - Dendritic cells modified with 6Ckine/IFNgamma fusion gene induce specific
      cytotoxic T lymphocytes in vitro.
AB  - BACKGROUND AND OBJECTIVE: [corrected] Dendritic cells play an important role in
      initiation and regulation of immune responses. Previous studies demonstrated that
      intratumoral administration of 6Ckine-modified DCs enhanced local and systemic
      antitumor effects. Herein we report the investigation of the specific CTL
      responses elicited by adenoviral 6Ckine/IFNgamma fusion gene-modified DCs in
      vitro. METHODS: Human monocyte-derived DCs were modified with an adenoviral
      vector encoding 6Ckine/IFNgamma fusion protein (Ad-6Ckine/IFNgamma), and then
      investigated the effect of 6Ckine/IFNgamma fusion protein on the maturation,
      cytokine and chemokine secretion of DCs, and their activities of recruiting and
      activating T cells in vitro were investigated. RESULTS: 6Ckine/IFNgamma fusion
      protein induced DC maturation characterized with the upregulation of CD83 and
      CCR7. And it up-regulated the expression of RANTES and IL-12p70, down-regulated
      that of IL-10 in DCs. Additionally, 6Ckine/IFNgamma markedly increased DC's
      recruiting ability for naive T cells, benefiting from the enhanced expression of
      chemokines 6Ckine and RANTES in DCs. Fusion gene-modified DCs significantly
      promoted the proliferation of autologous T cells, induced Th1 differentiation by
      upregulating the expression of IL-2 and T-bet in T cells, and increased specific
      cytotoxicity of CTLs against specific tumor cells, HepG2 or LoVo cells,
      respectively. CONCLUSION: Combining the effects of 6Ckine and IFNgamma, Ad
      6Ckine/IFNgamma modified DCs induced enhanced CTL responses in vitro, which
      indicated that Ad-6Ckine/IFNgamma modified DCs might be used as an adjuvant to
      trigger an effective antitumor immune response.

PMID- 17503044
TI  - Release of ischaemia prior to wound closure in total knee arthroplasty: a better
      method?
AB  - We included 46 total knee arthroplasties (43 patients) in a prospective,
      randomised study, dividing them into two groups: group A (23 knees, 21 patients)
      in which the ischaemia was released prior to wound closure allowing control of
      bleeding and group B (23 knees, 22 patients) releasing the tourniquet after
      suturing and bandaging. We compared the haemoglobin before surgery and at 24 and
      48 h postoperatively, the total blood loss and the transfusions that were needed.
      Student's t-test was used to analyse the data. The results we obtained were as
      follows: preoperative haemoglobin in group A was 14.21 g/dl and group B 14.28
      g/dl; haemoglobin at 24/48 h for group A was 10.04/10.1 g/dl and group B
      10.28/10.3 g/dl; total blood loss was 743.2 cc for group A and 692.5 cc for group
      B; the mean number of blood units transfused were 2 in group A and 1.8 in group
      B. No statistical differences were found in the data analysed, but one of the
      complications in group B was major blood loss right after surgery that needed
      reintervention. We assume that this could have been avoided if the tourniquet had
      been released beforehand. We conclude that releasing ischaemia prior to wound
      closure does not demonstrate a statistical difference, but like other authors, we
      found clinical advantages suggesting the need of further study of this situation.

PMID- 17503045
TI  - Late spontaneous remissions in severe adult autoimmune thrombocytopenia.
AB  - We report on four cases (three women, one man, age at diagnosis 26-61 years) with
      severe autoimmune thrombocytopenia (AITP) who were refractory to initial steroid
      therapy (n = 4), to subsequent splenectomy (n = 2), azathioprine (n = 1), and
      cyclosporine (n = 1). Over years they received low-dose continuous or
      intermittent steroid therapy. After 6 to 31 years these patients achieved a
      "spontaneous" complete remission (CR) (n = 3) or partial remission (PR) (n = 1)
      unrelated to any specific second or third line treatment; CR/PR are sustained for
      0.5+ to 9+ years. These data indicate that spontaneous remissions may occur in
      AITP even after a long duration of the disease.

PMID- 17503046
TI  - Hemoglobin H disease induced by the common SEA deletion and the rare hemoglobin
      Quong Sze in a Thai female: longitudinal clinical course, molecular
      characterization, and development of a PCR/RFLP-based detection method.
AB  - We report on a Thai female patient who presented with hypochromic microcytic
      anemia, hepatosplenomegaly, and failure to thrive since 3 years of age.
      Hematological and hemoglobin (Hb) analysis were consistent with a clinical
      diagnosis of Hb H disease. However, no abnormal Hb fraction had ever been
      detected. During the 20 years of follow-up, this patient experienced several
      episodes of hemolytic crisis, which worsened her anemia, necessitating blood
      transfusion. Recently, we identified Hb Quong Sze (Hb QS), a highly unstable
      globin gene mutation affecting codon 125 (CTG-->CCG) of alpha(2) globin gene in
      trans with the commonest alpha(0) thalassemia (-(SEA)) in the patient. This
      report highlights the clinical significance of Hb QS in Southeast Asians, as
      previously almost all of the patients described with this variant were of Chinese
      origin.

PMID- 17503047
TI  - Improvement in intraperitoneal intraoperative cisplatin exposure based on
      pharmacokinetic analysis in patients with ovarian cancer.
AB  - Ovarian cancer is the leading cause of gynecological cancer-related death in
      Western countries. The present treatment standards for ovarian cancer are based
      on the association of debulking surgery with platinum-based chemotherapy. Another
      strategy that could be further investigated is intraperitoneal chemotherapy (IP).
      We previously described that the 2-h administration of intraoperative IP
      cisplatin did not reach satisfactory concentrations. In the present study, we
      present the results of a pharmacokinetic analysis performed after two consecutive
      1-h IP 30 mg/l cisplatin administrations. Twenty-seven patients with advanced
      epithelial cancer classified FIGO stage IIIC were included in the study. Blood
      and IP samples were taken over a 24-h period, during and after IP treatment. Both
      total and ultrafiltered (Uf) platinum (Pt) concentration levels were analyzed.
      Biological and clinical toxicities were also recorded. With this strategy, IP Pt
      concentrations stayed above the target concentration (10 mg/l) for a satisfactory
      length of time. The serum Pt concentrations were higher than those observed with
      the "one-bath" protocol and they induced the occurrence of recoverable renal
      toxicities (3 grade 1, 7 grade 2 and 4 grade 3). The best predictive parameter
      for renal failure was the total Pt 24-h Area Under the Curve (AUC) with a
      threshold value of 25 mg h/l RR = 0.31 (95% CI 0.13 - 0.49, P < 0.01).
      Administration of an increased amount of cisplatin is feasible and a satisfactory
      level of IP Pt concentrations is obtained. However, this improvement is
      associated with an increase in serum Pt levels and resulting renal toxicities. An
      attractive solution would be to decrease Pt transfer from peritoneum to
      bloodstream. A phase 1 study using intraoperative IP epinephrine in order to
      decrease this transfer is presently being carried out.

PMID- 17503048
TI  - Interferon gamma assay for detecting latent tuberculosis infection in rheumatoid
      arthritis patients during infliximab administration.
AB  - In rheumatoid arthritis (RA) patients treated with infliximab (IFX), QuantiFERON
      TB Gold (QFT-G), an interferon gamma assay for diagnosing tuberculosis infection,
      was performed to compare its effectiveness to conventional diagnostic procedures
      (tuberculin skin test, imaging and medical history) in diagnosing latent
      tuberculosis infection (LTBI). QFT-G was measured bimonthly in 14 rheumatoid
      arthritis patients during IFX treatment. Seven of 14 patients were confirmed as
      LTBI positive by at least one method. Of these, four were positive on QFT-G
      during the study period, and two were positive before the start of IFX
      administration. For two of the four QFT-G-positive patients, LTBI was diagnosed
      only by QFT-G. The rate of agreement between QFT-G and conventional procedures
      was 64.3%. A total of 5% of QFT-G tests were impossible to judge due to decreased
      reactions in the positive control. These results suggest that QFT-G is able to
      detect LTBI in RA patients overlooked by conventional methods. Conventional
      procedures and QFT-G should be employed in parallel, and LTBI should be assumed
      when one technique gives a positive result.

PMID- 17503049
TI  - Isolation of two highly active soybean (Glycine max (L.) Merr.) promoters and
      their characterization using a new automated image collection and analysis
      system.
AB  - A novel automated image collection and analysis system was used to compare two
      new soybean (Glycine max (L.) Merr.) promoters with the cauliflower mosaic virus
      35S (CaMV35S) promoter, which was used as an expression standard. For expression
      comparisons, various permutations of a soybean polyubiquitin (Gmubi) promoter, a
      soybean heat shock protein 90-like (GmHSP90L) promoter and the CaMV35S promoter
      were placed upstream of a green fluorescent protein (gfp) gene. DNA constructs
      were introduced via particle bombardment into excised cotyledons of germinating
      lima bean (Phaseolus lunatus L.) seeds, which were arranged in Petri dishes for
      automated image capture and image analysis. The automated system allowed
      monitoring and quantification of gfp gene expression in the same piece of tissue
      over time. The Gmubi promoter, with its intronic region intact, showed the
      highest expression that was over five times stronger than the CaMV35S promoter.
      When an intronic region was removed from the Gmubi promoter, GFP expression was
      reduced, but was still over two times greater than with the CaMV35S promoter. The
      full-length soybean GmHSP90L promoter was four times stronger than the CaMV35S
      promoter. Truncation of the GmHSP90L promoter resulted in stepwise decreases in
      promoter strength, which appear to correspond to removal of regulatory elements.
      Automated image capture and analysis allowed the rapid and efficient evaluation
      of these new promoters.

PMID- 17503050
TI  - Impingement syndromes of the ankle.
AB  - Ankle impingement syndromes are categorised according to their anatomical site
      around the tibiotalar joint. Anterolateral, anterior and posterior ankle
      impingement has been extensively described in the orthopaedic and radiology
      literature with more recent studies describing posteromedial and anteromedial
      impingement. This article aims to demonstrate the potential spectrum of imaging
      findings for each ankle impingement syndrome as well as the relative
      contributions of ultrasound and MR imaging for diagnosis and image-guided
      treatment.

PMID- 17503051
TI  - The tiny difference between foraging and communication buzzes uttered by the
      Mexican free-tailed bat, Tadarida brasiliensis.
AB  - Echolocating insectivorous bats consummate prey captures using a distinct vocal
      motor pattern commonly known as the terminal or feeding buzz, which is widely
      considered a fixed motor pattern executed independently of auditory feedback
      influences. The Mexican free-tailed bat, Tadarida brasiliensis, offers an
      opportunity to explore the role of sensory feedback in buzzing because they emit
      similar buzzes both in flight during foraging and while stationary as
      communication sounds. Here we compared the spectral and temporal patterns of
      foraging and communication buzzes to address whether or not auditory feedback may
      influence buzz patterns. We found that while foraging buzzes uttered in open
      space were composed of generic FM calls, communication buzzes were composed of an
      adapted CF-FM call similar to the call type used by T. brasiliensis when
      navigating in confined spaces. This provides the first evidence that some bats
      can make significant context-dependent changes in the spectral parameters of
      calls within their buzz. We also found that inter-pulse intervals, but not call
      durations, were different within the two buzz types. These observations indicate
      that though a common pattern generator hierarchically organizes all buzzes, T.
      brasiliensis retains a significant capacity to adapt the spectral and temporal
      patterns of elements within its buzzes.

PMID- 17503052
TI  - Release mechanism of sex pheromone in the female gypsy moth Lymantria dispar: a
      morpho-functional approach.
AB  - A morpho-functional investigation of the sex pheromone-producing area was
      correlated with the pheromone release mechanism in the female gypsy moth
      Lymantria dispar. As assessed by male electroantennograms (EAG) and morphological
      observations, the pheromone gland consists of a single-layered epithelium both in
      the dorsal and ventral halves of the intersegmental membrane between the 8th and
      9th abdominal segments. By using the male EAG as a biosensor of real-time release
      of sex pheromone from whole calling females, we found this process time coupled
      with extension movements of the ovipositor. Nevertheless, in females in which
      normal calling behavior was prevented, pheromone release was detected neither in
      absence nor in presence of electrical stimulation of the ventral nerve
      cord/terminal abdominal ganglion (TAG) complex. Tetramethylrhodamine-conjugated
      dextran amine stainings also confirm the lack of any innervation of the gland
      from nerves IV to VI emerging from the TAG. These findings indicate that the
      release of sex pheromone from the glands in female gypsy moths is independent of
      any neural control exerted by the TAG on the glands, at least by way of its three
      most caudally located pairs of nerves, and appears as a consequence of a
      squeezing mechanism in the pheromone-producing area.

PMID- 17503053
TI  - Neurophysiological response selectivity for conspecific songs over synthetic
      sounds in the auditory forebrain of non-singing female songbirds.
AB  - Female choice plays a critical role in the evolution of male acoustic displays.
      Yet there is limited information on the neurophysiological basis of female
      songbirds' auditory recognition systems. To understand the neural mechanisms of
      how non-singing female songbirds perceive behaviorally relevant vocalizations, we
      recorded responses of single neurons to acoustic stimuli in two auditory
      forebrain regions, the caudal lateral mesopallium (CLM) and Field L, in
      anesthetized adult female zebra finches (Taeniopygia guttata). Using various
      metrics of response selectivity, we found consistently higher response strengths
      for unfamiliar conspecific songs compared to tone pips and white noise in Field L
      but not in CLM. We also found that neurons in the left auditory forebrain had
      lower response strengths to synthetics sounds, leading to overall higher neural
      selectivity for song in neurons of the left hemisphere. This laterality effect is
      consistent with previously published behavioral data in zebra finches. Overall,
      our results from Field L are in parallel and from CLM are in contrast with the
      patterns of response selectivity reported for conspecific songs over synthetic
      sounds in male zebra finches, suggesting some degree of sexual dimorphism of
      auditory perception mechanisms in songbirds.

PMID- 17503054
TI  - Karman vortex street detection by the lateral line.
AB  - Fish use the lateral line system for prey detection, predator avoidance,
      schooling behavior, intraspecific communication and spatial orientation. In
      addition the lateral line may be important for station holding and for the
      detection of the hydrodynamic trails (vortex streets) generated by swimming fish.
      We investigated the responses of anterior lateral line nerve fibers of goldfish,
      Carassius auratus, to unidirectional water flow (10 cm s(-1)) and to running
      water that contained a Karman vortex street. Compared to still water conditions,
      both unidirectional water flow and Karman vortex streets caused a similar
      increase in the discharge rate of anterior lateral line nerve fibers. If exposed
      to a Karman vortex street, the amplitude of spike train frequency spectra
      increased at the vortex shedding frequency. This increase was especially
      pronounced if the fish intercepted the edge of a Karman vortex street. Our data
      show that the vortex shedding frequency can be retrieved from the responses of
      anterior lateral line nerve fibers.

PMID- 17503055
TI  - Neuroprotective effects of high-dose vs low-dose melatonin after blunt sciatic
      nerve injury.
AB  - INTRODUCTION: Melatonin, the secretory product of the pineal gland, has potent
      antioxidant properties. The aim of this study was to compare the effects of low
      dose (10 mg/kg) vs high-dose (50 mg/kg) melatonin on early lipid peroxidation
      levels and ultrastructural changes in experimental blunt sciatic nerve injury
      (SNI). We believe this to be the first study to assess the dose-dependent
      neuroprotective effects of melatonin after a blunt peripheral nerve injury.
      MATERIALS AND METHODS: Rats were randomly allocated into 5 groups of 10 animals
      each. The SNI only rats underwent a nerve injury procedure. The SNI plus vehicle
      group received SNI and intraperitoneal injection of vehicle (diluted ethanol) as
      a placebo. The SNI plus low-dose or high-dose melatonin groups received
      intraperitoneal melatonin at doses of 10 mg/kg or 50 mg/kg, respectively.
      Controls had no operation, melatonin or vehicle injection. SNI was induced by
      clamping the sciatic nerve at the upper border of the quadratus femoris for 2
      min. RESULTS: Sciatic nerve samples were harvested 6 h after nerve injury and
      processed for biochemical and ultrastructural analysis. Trauma increased the
      lipid peroxidation of the sciatic nerve by 3.6-fold (153.85 +/- 18.73 in SNI only
      vs 41.73 +/- 2.23 in control rats, P < 0.01). Low (P = 0.02) and high (P < 0.01)
      doses of melatonin attenuated the nerve lipid peroxidation by 25% and 57.25%,
      respectively (65.76 +/- 2.47 in high-dose vs 115.08 +/- 7.03 in low-dose
      melatonin groups). DISCUSSION: Although low-dose melatonin reduced trauma-induced
      myelin breakdown and axonal changes in the sciatic nerve, high-dose melatonin
      almost entirely neutralized any ultrastructural changes. CONCLUSION: Our results
      suggest that melatonin, especially at a dose of 50 mg/kg, has a potent
      neuroprotective effect and can preserve peripheral neural fibers from lipid
      peroxidative damage after blunt trauma. With further investigations, we hope that
      these data may prove useful to clinicians who treat patients with nerve injuries.

PMID- 17503056
TI  - Post traumatic prepubertal high-flow priapism: a rare occurrence.
AB  - High-flow or arterial priapism is an uncommon condition resulting from perineal
      or penile trauma. The classical features are a painless erection of the cavernous
      bodies while the corpus spongiosum stays flaccid. This case highlights a 11-year
      old boy who presented with painless semi rigid erection of 3 days duration
      following a blunt skateboard injury to his perineum. Following failed
      conservative treatment, the patient underwent bilateral internal pudendal
      angiography with localization and embolization. Follow up in 1 month showed
      patient to have normal nocturnal and reflexogenic erections. Medical and surgical
      treatments for high-flow priapism have been described in literature with varying
      degree of success and complications. The current accepted standard of care is
      pelvic angiography and super-selective embolization of internal pudendal artery.

PMID- 17503057
TI  - Is mobile testis a true pathological condition due to a gubernaculum abnormality?
AB  - The present study was conducted to clarify whether a gubernaculum abnormality
      exists in mobile testis or not. Testicular fixation was performed in 57 patients
      with mobile testis with a mean age of 3.6 years (range; 7 months-12 years).
      Twenty-six patients were bilateral and 31 patients were unilateral cases. Control
      gubernaculum findings were obtained from 12 patients with hydrocele testis with a
      mean age of 3.3 years (1.6-5 years). In 12 patients with hydrocele testis, the
      gubernaculum was found from the lower third of the testis to the scrotal base
      inside the tunica vaginalis (plica gubernaculi), while outside the tunica
      vaginalis pars infravaginalis gubernaculi further extended into the scrotal base.
      On the other hand, in 57 patients with mobile testis, the gubernaculum was easily
      identified only inside the tunica vaginalis without any recognizable gubernaculum
      outside the tunica vaginalis. In 31 unilateral patients, associated anomalies of
      the contralateral testis were found in 13 patients (42%); 11 cases with
      undescended testis and two cases with ectopic testis. These results suggest that
      mobile testis might therefore be a true pathological condition, which were highly
      associated with contralateral testicular morbidities.

PMID- 17503058
TI  - Developmental changes of the adrenergic network in the myenteric plexus of the
      porcine small bowel.
AB  - Knowledge about the foetal development of the normal enteric nervous system (ENS)
      is crucial for the understanding of congenital and acquired functional
      abnormalities of the gut. The ENS is the largest and most complex division of the
      peripheral nervous system and consists of intrinsic and extrinsic components.
      Although previous studies have described sympathetic innervation of the myenteric
      plexus, little is known regarding its age-related changes. The aim of this study
      was to investigate the age-related changes in the sympathetic innervation of the
      myenteric plexus. Whole mount and paraffin sections of the small bowel specimens
      from six different age groups (60 and 90 days gestation; newborn; 4 and 12 weeks
      old; and adult) were stained using tyrosine hydroxylase immunohistochemistry.
      Specimens were then analysed using fluorescence and laser scanning microscopy in
      detail. The tyrosine hydroxylase positive nerve fibres were first seen within the
      myenteric plexus at 90 days of gestation (E90). There was a significant increase
      in nerve fibres and varicosities observed from E90 to 12 weeks of age and
      stabilisation thereafter. The degree of varicosities around the ganglia, clearly
      seen on the whole-mount preparations, was also noted to increase up to 12 weeks
      of age, after which time there was no general variation noted into adulthood. Our
      findings show, for the first time, that sympathetic innervation of the myenteric
      plexus starts in the last quarter of gestation and continues till 12 weeks of
      age. Segmental sympathetic denervation, following bowel resection and
      anastomosis, during this developmental period may explain the motility
      dysfunction seen in newborn infants operated for necrotising enterocolitis, bowel
      atresia and Hirschsprung's disease.

PMID- 17503059
TI  - Bilateral anterior glenohumeral dislocation in a horse rider: a case report and a
      review of the literature.
AB  - A case of bilateral anterior glenohumeral dislocation in a middle aged horse
      rider was presented. The patient was an amateur rider who sustained the injury
      when the horse reared suddenly. The rider fell back from the saddle while holding
      the halter. The shoulders were dislocated by a violent traction when shoulders
      were in internal rotation and flexion in sagittal plane and slight abduction in
      coronal plane. To the best of our knowledge this case is the third glenohumeral
      dislocation by forward traction. A review of the literature is presented.

PMID- 17503060
TI  - Femoral head avascular necrosis after interlocking nail of a femoral shaft
      fracture in a male adult: a case report.
AB  - Reamed interlocking nail through the piriformis fossa remains the golden standard
      for treatment of femoral shaft fracture. Fracture healing rates are 95-99%, and
      infection rates less than 1% (Clawson et al. in J Bone Joint Surg (Am) 53:681
      692, 1971; Winquist et al. in J Bone Joint Surg (Am) 66:529-539, 1984; Brumback
      et al. in J Bone Joint Surg (Am) 70:1453-1462, 1988). Previous reports recognize
      avascular necrosis of the femoral head as a complication of antegrade
      interlocking nail in the adolescent (Beaty et al. in J Pediatr Orthop 14:178-183,
      1994; Mileski et al. in J Bone Joint Surg (Am) 76:1706-1708, 1994; O'Malley et
      al. in J Pediatr Orthop 15:21-23, 1995; Buckaloo et al. in J Southern Orthop
      Assoc 6(2):97-100, 1997). This report describes a male adult who developed
      avascular necrosis of the femoral head after an open antegrade interlocking nail
      of a proximal third femoral shaft fracture. To our knowledge, there is no similar
      report in the English medical literature.

PMID- 17503061
TI  - A rare actinomycosis of humerus: an unusual location and a diagnostic dilemma. A
      case report.
AB  - BACKGROUND: Isolated actinomycosis of the humerus is a very rare entity. METHOD:
      A 30-year-old male had an erythematous plaque with a pus-(minimal) discharging
      sinus over left lower arm. The patient had no discharge of sulphur granules from
      the sinus. The patient had raised ESR with a single lytic lesion with minimal
      sclerosis and inconspicuous periosteal reaction on radiographs. Such atypical
      clinical and radiological features lead to initial wrong diagnosis of
      tuberculosis. A diagnosis of Actinomycosis of humerus became possible after
      demonstration of filamentous bacilli in culture and on histopathology from the
      sulphur grains obtained by open biopsy. RESULT: The patient recovered completely
      after administering PenicillinG 24 million units intravenous for 7 days followed
      by 1.2 g of oral amoxicillin in three divided doses for 3 months and did not show
      any recurrence during last 2 years of follow up. CONCLUSION: Surgeons should be
      aware of this rare entity and difficulty in its diagnosis due to its variable
      manifestations, including confusion with highly endemic tuberculous infection.
      Awareness of full spectrum of the diseases and careful evaluation in individual
      cases will expedite diagnosis and avoid unnecessary surgical interventions.

PMID- 17503062
TI  - Slotted acetabular augmentation for the treatment of residual hip dysplasia in
      adults: early results of 12 patients.
AB  - INTRODUCTION: Different pelvic osteotomies and various shelf procedures are used
      for the operative treatment of hip dysplasia. Slotted acetabular augmentation
      (SAA) is a well-established technique for the treatment of children and
      adolescents with hip dysplasia. It has not been widely accepted for treating hip
      dysplasia in adults although good outcomes have been reported with other
      augmentation techniques in adults. MATERIALS AND METHODS: Since 1997, SAA has
      been used for the prevention of hip arthrosis in 14 dysplastic hips in 12 female
      patients. The median age at operation was 38.5 (17-42) years; the median follow
      up period was 4 (1-8) years. The patients were evaluated on the basis of
      radiographic, biomechanical and clinical data prior to surgery and at follow-up.
      RESULTS: The median centre-edge angle of Wiberg increased from 9 degrees (1-26)
      before the operation to 43 degrees (31-55) at the latest follow-up (P < 0.001).
      The median peak stress on the weight-bearing area of the hip, calculated
      mathematically, was reduced from 14.9 (6.3-28-1) MPa prior to the operation to
      4.1 (3-6.1) MPa at the latest follow-up (P < 0.001); the median Harris Hip Score
      increased from 60 (45-98) points preoperatively to 93 (49-100) points at the
      follow-up (P < 0.001). There was no difference between the preoperative and
      follow-up hip joint-space width (P = 0.2). CONCLUSION: There were no
      postoperative complications. In our series, the procedure has proved reliable and
      safe. Its advantages include symptomatic pain relief, adequate acetabular roof
      coverage and reduced peak stress on the weight bearing area of the hip. It can be
      used to postpone the development of hip arthrosis in adults with acetabular
      dysplasia.

PMID- 17503063
TI  - Bilateral femoral neck stress fractures following total knee arthroplasty: a case
      report and review of literature.
AB  - Stress fracture of the femoral neck following total knee arthroplasty (TKA) is an
      uncommon complication with only 20 cases having been described in English
      literature so far. Stress fractures of femoral neck occurring simultaneously on
      both sides following a bilateral total knee replacement is an exceptional
      occurrence, which to the best of our knowledge, has not been described
      previously. We describe a patient suffering from osteoarthritis of both knees,
      who was treated with bilateral total knee arthroplasty simultaneously. He
      developed spontaneous fractures of femoral neck on both sides 9 months following
      the total knee replacement in the absence of any known risk factors for stress
      fractures. He was treated with bipolar hemi replacement arthroplasty for
      displaced fracture on one side and closed reduction/internal fixation on the
      undisplaced side. A high index of suspicion is needed to diagnose this unusual
      complication of total knee arthroplasty before the fracture displaces
      necessitating a prosthetic replacement.

PMID- 17503064
TI  - Two novel mutations of the ATP2C1 gene in Chinese patients with Hailey-Hailey
      disease.
AB  - Hailey-Hailey disease (HHD; OMIM 169600) is an autosomal dominant blistering
      disease. Pathogenic mutations in ATP2C1 encoding the human secretory pathway
      Ca(2+)/Mn(2+)-ATPase protein 1 (hSPCA1) have been identified since 2000. The aim
      of this study was to report a Chinese pedigree and a sporadic case of HHD and to
      explore the genetic mutations. The Chinese pedigree and the sporadic case of
      typical HHD were subjected to mutation detection of ATP2C1. The 27 coding exons
      and their flanking sequences were amplified and sequenced. The heterozygous C to
      T transition at nucleotide 2753 in exon 26 and G to T transition at nucleotide
      2090 in exon 21 of the ATP2C1 gene were identified in a pedigree and a sporadic
      case of HHD, respectively. The C2753T transition resulted in a novel nonsense
      mutation of glutamine codon (CAG) to a stop codon (TAG) at amino acid residue 865
      (Q865X) and the G2090T transition resulted in a novel missense mutation of
      glycine condon (GGA) to Valine (GUA) at amino acid residue 645 (G645V) in hSPCA1.
      This study should be useful for genetic counseling and prenatal diagnosis for
      affected families and in expanding the repertoire of ATP2C1 mutations underlying
      HHD.

PMID- 17503065
TI  - Evaluation of vertiginous children.
AB  - Our objective was to evaluate, using a structured approach method, the history
      and findings in vertiginous children as compared with a group of healthy
      children. We evaluated 24 vertiginous children (15 girls, 9 boys) with episodes
      of true vertigo of unknown etiology and 12 healthy age- and gender-matched
      controls. A detailed medical history was obtained using a structured approach
      technique. Vertiginous and healthy children underwent general and otoneurologic
      examinations, including audiogram, electronystagmography, and tympanometry, at
      the Helsinki University Hospital ENT clinic. Characteristics of patient histories
      and clinical findings were compared between the groups. The vertiginous children
      reported significantly more head traumas and headaches than the controls. The
      structured data collection approach improved the evaluation process. The
      predominant diagnoses were benign paroxysmal vertigo of childhood, otitis media
      related vertigo, and migraine-associated dizziness.

PMID- 17503066
TI  - Topical treatment of acute otitis externa: clinical comparison of an antibiotics
      ointment alone or in combination with hydrocortisone acetate.
AB  - The study was designed to investigate the potential contribution of
      hydrocortisone acetate to the efficacy and safety of an antibiotics ointment in
      the treatment of acute otitis externa (AOE). In a double-blind study 151 patients
      with a unilateral acute bacterial otitis externa were randomized either to
      receive an ointment with polymyxin-B sulfate (7,500 I.E./g) + bacitracin (300
      I.E./g) alone (AB) or the same antibiotic ointment with 10 mg hydrocortisone
      acetate/g ointment (AB + HC). Primary efficacy endpoint was the change of an
      aggregate clinical symptom score (CSS) (subscores: redness, swelling, pain and
      secretion) found at Visit 2 versus baseline (Visit 1). Secondary outcome
      parameters were the change of the CSS from Visit 1 to the study termination, and
      the changes in the subscores and of a visual analog scale for pain. In the group
      treated with AB + HC, significantly more patients with severe redness [14 (56%)
      vs. 7 (28%), P = 0.045] or severe secretion [23 (70%) vs. 10 (40%), P = 0.024] at
      inclusion were symptom-free at the last visit. Fewer pain-relieving tablets (1.1
      +/- 2.2 vs. 2.3 +/- 4.6 paracetamol tablets) were used in the AB + HC-group. In
      the steroid group there was a slightly larger though not significant reduction in
      CSS at Visit 2 and Visit 3 versus baseline. Similar results were documented for
      redness, pain and secretion. No serious adverse events occurred. Both ointments
      are effective and safe in the topical treatment of AOE. Hydrocortisone acetate
      combined with the antibiotics improved individual symptoms better as did the
      steroid-free ointment.

PMID- 17503067
TI  - Visualizing the dynamics of chromosome structure formation coupled with DNA
      replication.
AB  - A basic question of cell biology is how DNA folds to chromosome. Numbers of
      examples have suggested the involvement of DNA replication in chromosome
      structure formation. To visualize and identify the dynamics of chromosome
      structure formation and to elucidate the involvement of DNA replication in
      chromosome construction, Cy3-2'-deoxyuridine-5'-triphosphate direct-labeled
      active replicating DNA was observed in prematurely condensed chromosomes (PCCs)
      under a confocal scanning microscope utilized with drug-induced premature
      chromosome condensation (PCC) technique that facilitates the visualization of
      interphase chromatin as condensed chromosome form. S-phase PCCs revealed clearly
      the drastic dynamics of chromosome formation that transits during S-phase from a
      'cloudy nebula' to numerous numbers of 'beads on a string' and finally to
      'striped arrays of banding structured chromosome' along with the progress of DNA
      replication. The number, distribution, and shape of replication foci were also
      measured in individual subphases of S-phase more precisely than reported
      previously; maximally, approximately 1,400 foci of 0.35 microm average radius
      size were scored at the beginning of the S-phase, and the number reduced to
      approximately 100 at the end of the S-phase. Drug-induced PCC clearly provided
      the new insight that eukaryote DNA replication is tightly coupled with the
      chromosome condensation/compaction for the construction of the higher-ordered
      structure of the eukaryote chromosome.

PMID- 17503068
TI  - Changes in multi-segmented body movements and EMG activity while standing on firm
      and foam support surfaces.
AB  - Postural control ensures stability during both static posture and locomotion by
      initiating corrective adjustments in body movement. This is particularly
      important when the conditions of the support surface change. We investigated the
      effects of standing on a compliant foam surface using 12 normal subjects (mean
      age 26 years) in terms of: linear movements at the head, shoulder, hip and knee;
      EMG activity of the tibialis anterior and gastrocnemius muscles and torques
      towards the support surface. As subjects repeated the trials with eyes open or
      closed, we were also able to determine the effects of vision on multi-segmented
      body movements during standing upon different support surface conditions. As
      expected, EMG activity, torque variance values and body movements at all measured
      positions increased significantly when standing on foam compared with the firm
      surface. Linear knee and hip movements increased more, relative to shoulder and
      head movements while standing on foam. Vision stabilized the head and shoulder
      movements more than hip and knee movements while standing on foam support
      surface. Moreover, vision significantly reduced the tibialis anterior EMG
      activity and torque variance during the trials involving foam. In conclusion, the
      foam support surface increased corrective muscle and torque activity, and changed
      the firm-surface multi-segmented body movement pattern. Vision improved the
      ability of postural control to handle compliant surface conditions. Several
      essential features of postural control have been found from recording movements
      from multiple points on the body, synchronized with recording torque and EMG.

PMID- 17503069
TI  - Formation and decay of sensorimotor and associative memory in object lifting.
AB  - The temporal dynamics of the formation and decay of the memory processes
      underlying the specification of force when lifting objects of either the same or
      different weight were investigated. Sensorimotor memory enables rapid force
      programming to the physical object properties. Associative memory may be used to
      establish a memory link between a colour cue and object weight. In experiment 1,
      subjects lifted a constant weight in sets of ten lifts 10 s, 5 min, 1 h and 24 h
      apart. In experiment 2, subjects learned to associate a colour to two different
      weights to be lifted in alternation within sets of ten lifts 10 s, 5 min, 1 h and
      24 h apart. Results of experiment 1 suggest that the memory related to the
      physical properties of a given object is rapidly established within a few lifts.
      However, there is a drift of accuracy of force programming that is observed as
      early as 10 s after the initial set of lifts. Results of experiment 2 imply that
      people are able to quickly establish an association between visual colour cues
      and particular object weights. Importantly, the formation of such memory appears
      to reduce the drift in accuracy observed in experiment 1 and provides the precise
      programming of grip and lift forces according to the physical object properties
      for up to 24 h.

PMID- 17503070
TI  - Permissive role of calcium on regulatory volume decrease in freshly isolated
      mouse cholangiocytes.
AB  - Calcium (Ca2+) pathways are important in cell volume regulation in many cells,
      but its role in volume regulatory processes in cholangiocytes is unclear. Thus,
      we have investigated the role of Ca2+ in regulatory volume decrease (RVD) in
      cholangiocytes using freshly isolated bile duct cell clusters (BDCCs) from normal
      mouse. No significant increase in [Ca2+]i was observed during RVD, while
      ionomycin and ATP showed significant increases. Confocal imaging also showed no
      significant changes in the levels or distributions of intracellular Ca2+ during
      RVD. Cell volume study by quantitative videomicroscopy indicated that removal and
      chelation of extracellular Ca2+ by ethylene glycol-bis (beta-aminoethyl ether)
      N,N,N-tetraacetic acid (EGTA) or administration of nifedipine did not affect RVD
      but verapamil significantly inhibited the RVD. Moreover, Ca2+ agonists or
      inhibitors of Ca2+ release from intracellular stores had no significant effect on
      RVD. However, 1,2-bis (2-aminophenoxy) ethane-N,N,N'N'-tetraacetic acid-AM (BAPTA
      AM) showed significant decreases in [Ca2+]i and significantly inhibited RVD,
      which was reversed with coadministration of valinomycin, suggesting that BAPTA-AM
      induced inhibition is due to potassium conductance or other cellular processes
      requiring permissive [Ca2+](i. These findings indicate that an increase in
      [Ca2+]i or extracellular Ca2+ is not required for RVD but Ca2+ has a permissive
      role in RVD of mouse cholangiocytes.

PMID- 17503071
TI  - Reduction in beta-myosin heavy chains in stunned myocardium as assessed by
      nondenaturing gel electrophoresis.
AB  - Myosin plays a key role in the structure and function of cardiac muscle. Three
      myosin isoenzymes (V(1), V(2), and V(3)) with different ATPase activities have
      been identified in mammalian ventricles based on their heavy chain constituents.
      The relative amount of myosin isoenzymes changes under physiological and
      pathological conditions. Until now, myosin isoenzymes have frequently been
      determined using either tube gel (nondenaturing) polyacrylamide gel
      electrophoresis (PAGE), or gradient or uniform sodium dodecyl sulfate
      (denaturing) PAGE. Both methods have disadvantages, e.g., a long running time. We
      developed, therefore, a uniform, nondenaturing PAGE with slab minigel format for
      analyzing the myosin isoenzymes in normoxic and stunned rabbit hearts. In
      normoxic hearts of adult rabbits, V(3) predominated over V(1) (46 vs 41%). In
      turn, in the stunned hearts, V(1) predominated over V(3) (70 vs 30%), and the
      heterodimeric V(2) was not anymore detectable. This alteration appears to result
      from a selective loss of myosin heavy chain (MHC)-beta. In parallel, the
      biochemical markers troponin I and creatine kinase were increased in the stunned
      hearts. We suggest that alterations of myosin isoenzymes in stunned myocardium
      can be monitored with native PAGE. The present analysis of myosin isoenzyme
      appears thus as a new tool for evaluating defects in MHC dimer formation in
      postischemic hearts.

PMID- 17503072
TI  - Anoxia-enhanced expression of genes isolated by suppression subtractive
      hybridization from pondweed (Potamogeton distinctus A. Benn.) turions.
AB  - Pondweed (Potamogeton distinctus A. Benn.), a monocot aquatic plant species, has
      turions, which are overwintering buds forming underground as an asexual
      reproductive organ. Turions not only survive for more than one month but also
      elongate under strict anoxia, maintaining high-energy charge by activation of
      fermentation. We cloned 82 cDNA fragments of genes, that are up-regulated during
      anoxic growth of pondweed turions, by suppression subtractive hybridization. The
      transcript levels of 44 genes were confirmed to be higher under anoxia than those
      in air by both Northern blot analysis and a semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR) method. A homology search for
      their nucleotide sequences revealed that some of them are highly homologous to
      known sequences of genes from other plants. They included alcohol dehydrogenase,
      pyruvate decarboxylase (PDC), glyceraldehyde-3-phosphate dehydrogenase (GAPDH),
      vacuolar H(+)-translocating pyrophosphatase and a plasma membrane intrinsic
      protein. Time courses of transcript accumulation of some genes under anoxia were
      different from those in air. The activity of PDC increased under anoxic
      conditions but the activities of GAPDH and pyrophosphatase remained constant
      after anoxic treatment. Anoxically up-regulated genes are possibly involved in
      physiological events to control energy production, pH regulation and cell growth
      under anoxia. These results suggest that transcriptional regulation of these
      genes serves as an essential part of survival and growth of pondweed turions
      under anoxia.

PMID- 17503073
TI  - The E subunit of photosystem I is not essential for linear electron flow and
      photoautotrophic growth in Arabidopsis thaliana.
AB  - PSI-E is part of the stromal side of photosystem I (PSI). In Arabidopsis
      thaliana, the two nuclear genes PsaE1 and PsaE2 code for PSI-E, and transcripts
      of PsaE1 are markedly more abundant than PsaE2 transcripts. Stable null alleles
      of the two PsaE genes, psae1-3 and psae2-1, were identified and characterised.
      The psae2-1 mutant exhibited wild-type like PSI-E abundance and photosynthetic
      performance, whereas in the psae1-3 mutant PSI-E accumulation was decreased by
      85%, together with an impaired thylakoid electron flow and plant growth rate. The
      psae1-3 psae2-1 double mutant totally lacked PSI-E but was still able to grow
      photoautotrophically, implying that PSI-E is not essential for PSI accumulation
      and thylakoid electron flow.

PMID- 17503074
TI  - Tomato fruit set driven by pollination or by the parthenocarpic fruit allele are
      mediated by transcriptionally regulated gibberellin biosynthesis.
AB  - We investigated the role of gibberellins (GAs) in the phenotype of parthenocarpic
      fruit (pat), a recessive mutation conferring parthenocarpy in tomato (Solanum
      lycopersicum L.). Novel phenotypes that parallel those reported in plants
      repeatedly treated with gibberellic acid or having a GA-constitutive response
      indicate that the pat mutant probably expresses high levels of GA. The retained
      sensitivity to the GA-biosynthesis inhibitor paclobutrazol reveals that this
      condition is dependent on GA biosynthesis. Expression analysis of genes encoding
      key enzymes involved in GA biosynthesis shows that in normal tomato ovaries, the
      GA20ox1 transcript is in low copy number before anthesis and only pollination and
      fertilization increase its transcription levels and, thus, GA biosynthesis. In
      the unpollinated ovaries of the pat mutant, this mechanism is de-regulated and
      GA20ox1 is constitutively expressed, indicating that a high GA concentration
      could play a part in the parthenocarpic phenotype. The levels of endogenous GAs
      measured in the floral organs of the pat mutant support such a hypothesis.
      Collectively, the data indicate that transcriptional regulation of GA20ox1
      mediates pollination-induced fruit set in tomato and that parthenocarpy in pat
      results from the mis-regulation of this mechanism. As genes involved in the
      control of GA synthesis (LeT6, LeT12 and LeCUC2) and response (SPY) are also
      altered in the pat ovary, it is suggested that the pat mutation affects a
      regulatory gene located upstream of the control of fruit set exerted by GAs.

PMID- 17503075
TI  - A cryptic intracellular green alga in Ginkgo biloba: ribosomal DNA markers reveal
      worldwide distribution.
AB  - Intracellular symbioses involving eukaryotic microalgae and a variety of
      heterotrophic protists and invertebrates are widespread, but are unknown in
      higher plants. Recently, we reported the isolation and molecular identification
      of a Coccomyxa-like green alga from in vitro cell cultures of Ginkgo biloba L.
      This alga resides intracellularly in an immature "precursor" form with a
      nonfunctional chloroplast, implying that algal photosynthetic activity has no
      role in this endosymbiosis. In necrotizing Ginkgo cells, precursors evolved into
      mature algae, proliferated, and were liberated into the culture medium after host
      cell bursting. In the present paper we demonstrate by molecular methods a
      worldwide distribution of the alga in planta. Endosymbiont-specific sequences of
      ribosomal DNA could be traced in Ginkgo tissues of each specimen examined from
      different geographic locations in Europe, North America, and Asia. The
      Ginkgo/Coccomyca association represents a new kind of intracellular, vertically
      inherited symbiosis. Storage bodies, probably of lipid nature, present in the
      cytoplasm of each partner suggest a possible involvement of the endosymbiont in
      metabolic pathways of its host.

PMID- 17503076
TI  - Insights into the evolutionary history of the vertebrate zic3 locus from a
      teleost-specific zic6 gene in the zebrafish, Danio rerio.
AB  - The Zic gene family of zinc-finger transcription factors includes five
      orthologues, zic1-5, that are common to the Euteleostian vertebrates (fish,
      frogs, birds, and mammals). The Zic genes have been implicated as regulators of a
      number of critical developmental processes, including neurulation, neuronal
      differentiation, neural crest specification, the establishment of left-right
      asymmetry, and regulation of cell proliferation. The different Zic genes encode
      proteins that are expressed in broadly overlapping spatial domains, have
      conserved DNA-binding domains that recognize a common motif, are capable of
      physical interactions, and can co-regulate one another's transcription. Thus, the
      transcriptional regulation of individual proteins and their effects on downstream
      targets must be assessed within the context of co-expression with other family
      members. We describe a novel gene, zic6, that is specific to the teleost fishes
      and lacks the lateral and rostral expression domains typical of the other Zic
      family members. We present evidence that zic6 is an ancestral locus arising by
      chromosomal duplication early in the Euteleostomi that was subsequently lost in
      the terrestrial vertebrates.

PMID- 17503077
TI  - Hepatitis B virus genotype E surface antigen detection with different
      immunoassays and diagnostic impact of mutations in the preS/S gene.
AB  - The major neutralizing epitope, the "a" determinant of the hepatitis B virus
      (HBV) genotype E surface antigen (HBsAg) is most divergent from that of genotype
      A, which is used for preparing monoclonal antibodies used in commercially
      available HBV reagents. To evaluate the performance of the latest generation of
      HBsAg detection assays with respect to genotype E HBsAg. Three commercial assays
      were evaluated using sera from 200 Nigerian patients compared to the preS/S
      sequence of DNA positive samples. Out of 200 samples, 61 and 103 gave concordant
      positive and negative results between the three HBsAg assays. Of 36 samples with
      discordant results, 35 were confirmed negative by neutralisation. One of the
      three assays showed significantly high rate of false positives (29 of 35). DNA
      positive samples with no detectable HBsAg or reduced HBsAg detection signals
      (<75% of mean signal obtained with HBsAg positive samples) revealed several
      mutations (V14A, F46S, N48T, L49R, I49T, D51G, A53V, P54L, Q82P, F83C, L127P,
      A184V, T189I, S204N, V224A), mostly outside the a-determinant. Several of these
      mutations are found as wild type nucleotides normally in genotype A and only
      exceptionally in genotype E. All three assays showed comparable sensitivities for
      genotype E HBsAg detection (98.4-100%) but differed considerably in specificity
      (84-99%). Failure to detect HBsAg antigen and differences in signal intensity
      were mainly associated with mutations in the preS/S gene outside the "a"
      determinant.

PMID- 17503078
TI  - Successful medical treatment of Candida endocarditis with liposomal amphotericin
      B without surgical intervention.

PMID- 17503079
TI  - Screening and early diagnosis of colorectal cancer in China: a 12 year retrospect
      (1994-2006).
AB  - Colorectal cancer is one of the most prevalent malignancies in the world. Chinese
      researchers and clinical doctors had been working hard in the last 12 years,
      exploring efficient and convenient methods for screening and early diagnosis. The
      12 years research works indicated that SFOBT plus colonoscopy was the best
      detecting protocol for mass screening of colorectal cancer. Serial combined
      testing for tumor markers plus colonoscopy is the most commonly used strategy for
      early diagnosis. However, still no optimum method for early diagnosis was
      generally accepted by most researchers. Due to intrinsic defects of the
      techniques, several screening and diagnostic methods should be combined to bring
      each advantage into full play, in order to elevate the diagnostic level of
      colorectal cancer.

PMID- 17503080
TI  - Novel germline mutations in BRCA2 gene among 96 hereditary breast and breast
      ovarian cancer families from Kerala, South India.
AB  - PURPOSE: Aim of the present study was to identify the genetic heterogeneity,
      prevalence and frequency of germline mutations of BRCA2 gene in Hereditary
      Breast/Ovarian cancer patients from Kerala, South India. METHODS: We analyzed 102
      Breast/Ovarian cancer patients from 96 breast and/ovarian cancer families for
      BRCA2 gene mutations using Conformation-Sensitive Gel Electrophoresis (CSGE)
      followed by sequencing. RESULTS: Sequence variations in BRCA2 gene were detected
      in 27 (26.4%) patients. Sixteen distinct sequence variants were detected of which
      11 were (69%) in exon 11. We have identified two novel disease-causing frameshift
      mutations (c.4642delAA and c.4926insGACC) in two unrelated patients. Apart from
      this, fourteen distinct sequence variants were detected in 25 breast/ovarian
      cancer patients of which 8 (57%) were also novel. These include nine missense
      mutations, one silent mutation, one-nonsense mutation and three intronic
      variants. CONCLUSIONS: The results of this study suggest that germline mutations
      of BRCA2 gene account for rather small proportion of Hereditary Breast/Ovarian
      cancer in Kerala, South India.

PMID- 17503081
TI  - Differential proteomic analysis of human colorectal carcinoma cell lines
      metastasis-associated proteins.
AB  - PURPOSE: Metastasis is a common phenomenon and the major lethal cause of
      colorectal carcinoma (CRC). To better comprehend the mechanism underlying CRC
      metastasis and to search for potential markers for predicting CRC metastasis, two
      CRC cell lines with different metastatic potentials, SW480 and SW620, were
      investigated by phenotypic analyses and proteomics technologies. METHODS: The
      surgical orthotopic implantation (SOI) technique was originally used to develop a
      reproducible colorectal cancer model in nude mice with stable tumor growth and
      metastasizing course. Furthermore, differential proteome analysis of two CRC cell
      lines was conducted using two-dimensional (2-D) gel electrophoresis combined with
      matrix-assisted laser desorption/time of flight (MALDI-TOF) mass spectrometry.
      RESULTS: Among the differential spots, 12 protein spots (11 proteins) were
      further identified using in-gel tryptic digestion and peptide mass fingerprinting
      (PMF). Interestingly, most of these proteins we identified have been reported to
      be associated with distinct aspect of tumor metastasis to some extent. Our
      immunohistochemistry assays of colorectal cancer revealed that heat shock protein
      (HSP) 27 overexpression relates to metastatic behavior of CRC cell. CONCLUSIONS:
      The protein profile between two colorectal cell lines with different potential
      metastasis displayed obvious differences. The results imply that various
      different proteins may lead to CRC metastasis together. HSP27 overexpression
      played an important role in metastasis and progression of CRC.

PMID- 17503082
TI  - Large volume loading to prevent cisplatin-induced nephrotoxicity during negative
      balance isolated pelvic perfusion.
AB  - PURPOSE: Negative-balance isolated pelvic perfusion (NIPP) is used to administer
      high doses of anticancer drugs such as cisplatin to patients with advanced cancer
      of the pelvic region. Although the drugs are intended to be specifically
      delivered to the pelvis, their leakage into the systemic circulation can cause
      acute renal failure. This study examines the loading volume required for
      preservation of renal function during anesthesia of NIPP. METHODS: Pelvic cancer
      patients were assigned to NIPP according to its enrollment criteria. Patients
      with heart failure, uncontrollable hypertension, renal failure, pulmonary disease
      or contraindication for the contrast media were excluded. We compared the current
      anesthesia management regime with a previous protocol, with regard to the loading
      volume and renal function as assessed by the calculated glomerular filtration
      rate (GFR). The correlation between the total loading volume and the GFR ratio
      (GFR after NIPP/GFR before NIPP) was evaluated to define adequate volume loading.
      RESULTS: The GFR ratios were 0.86 +/- 0.29 and 1.12 +/- 0.25 for the previous and
      current procedures, respectively. The regression line showed that a minimum
      loading volume of 28.8 ml kg(-1) h(-1) was required to maintain a GFR ratio of >
      or =1. CONCLUSIONS: A large volume infusion preserves the GFR despite high-dose
      cisplatin administration by NIPP.

PMID- 17503084
TI  - Male-to-female sex reversal associated with an approximately 250 kb deletion
      upstream of NR0B1 (DAX1).
AB  - Deletion of the dosage sensitive gene NR0B1 encoding DAX1 on chromosome Xp21.2
      results in congenital adrenal hypoplasia (AHC), whereas NR0B1 duplication in
      46,XY individuals leads to gonadal dysgenesis and a female phenotype. We describe
      a 21-year-old 46,XY female manifesting primary amenorrhea, a small immature
      uterus, gonadal dysgenesis, and notably absent adrenal insufficiency with a
      submicroscopic (257 kb) deletion upstream of NR0B1. We hypothesize that loss of
      regulatory sequences may have resulted in position effect up-regulation of DAX1
      expression, consistent with phenotypic consequences of NR0B1 duplication. We
      propose that this genomic region and by extension those surrounding the dosage
      sensitive SRY, SOX9, SF1, and WNT-4 genes, should be examined for copy-number
      variation in patients with sex reversal.

PMID- 17503085
TI  - A TNF region haplotype offers protection from typhoid fever in Vietnamese
      patients.
AB  - The genomic region surrounding the TNF locus on human chromosome 6 has previously
      been associated with typhoid fever in Vietnam (Dunstan et al. in J Infect Dis
      183:261-268, 2001). We used a haplotypic approach to understand this association
      further. Eighty single nucleotide polymorphisms (SNPs) spanning a 150 kb region
      were genotyped in 95 Vietnamese individuals (typhoid case/mother/father trios). A
      subset of data from 33 SNPs with a minor allele frequency of >4.3% was used to
      construct haplotypes. Fifteen SNPs, which tagged the 42 constructed haplotypes
      were selected. The haplotype tagging SNPs (T1-T15) were genotyped in 380
      confirmed typhoid cases and 380 Vietnamese ethnically matched controls. Allelic
      frequencies of seven SNPs (T1, T2, T3, T5, T6, T7, T8) were significantly
      different between typhoid cases and controls. Logistic regression results support
      the hypothesis that there is just one signal associated with disease at this
      locus. Haplotype-based analysis of the tag SNPs provided positive evidence of
      association with typhoid (posterior probability 0.821). The analysis highlighted
      a low-risk cluster of haplotypes that each carry the minor allele of T1 or T7,
      but not both, and otherwise carry the combination of alleles *12122*1111 at T1
      T11, further supporting the one associated signal hypothesis. Finally,
      individuals that carry the typhoid fever protective haplotype *12122*1111 also
      produce a relatively low TNF-alpha response to LPS.

PMID- 17503086
TI  - Expression of KiSS-1 in rat oviduct: possible involvement in prevention of
      ectopic implantation?
AB  - The mammalian oviduct is a crucial site for essential postovulatory events in the
      female reproductive system. These events are, in part, accomplished by clear-cut
      oviductal segmentation, which helps to provide appropriate epithelial and fluid
      microenvironments. Early embryonic development and the timely transport of the
      embryo to the uterus must be promoted, but implantation within the oviduct itself
      must be avoided. Indeed, the rarity of extra-uterine pregnancies in laboratory
      animals strongly suggests that active mechanisms operate to prevent ectopic
      implantation. Kisspeptins, products of the KiSS-1 gene, have been proposed as
      physiological regulators of uterine implantation by limiting the invasion of the
      trophoblast into the maternal decidua. We describe here the patterns of
      expression of the KiSS-1 gene and of kisspeptin immunoreactivity (IR) in the rat
      oviduct. KiSS-1 mRNA is readily detectable in oviduct samples from all phases of
      the estrous cycle, whereas kisspeptin-IR is detected in rat oviduct with a
      regionalized pattern of distribution, viz., strong expression in the isthmus,
      faint signals in the proximal ampulla, and a lack of immunostaining in the
      fimbriated infundibulum and interstitial portion. When positive, IR has been
      localized at the adluminal surface and the cytoplasmic domain of secretory cells.
      Of note, KiSS-1 expression (at the mRNA and protein levels) shows cycle-related
      changes with peak expression in proestrus/estrus and lower levels at
      metestrus/diestrus. This knowledge of the regional- and cycle-specific pattern of
      expression of KiSS-1 in rat oviduct should open up the possibility of a
      physiological role of kisspeptins in the prevention of ectopic (tubal)
      implantation.

PMID- 17503087
TI  - Photic induction of c-Fos in enkephalin neurons of the rat intergeniculate
      leaflet innervated by retinal PACAP fibres.
AB  - The brain's biological clock, located in the suprachiasmatic nucleus (SCN), is
      synchronised with the cyclic environment by photic and non-photic cues. Photic
      information to the SCN is mediated by pituitary adenylate-cyclase-activating
      polypeptide (PACAP)-containing retinal ganglion cells (RGCs), whereas non-photic
      input originates primarily from neuropeptide Y (NPY) cells in the ipsilateral
      thalamic intergeniculate leaflet (IGL). RGCs also seem to project to the IGL,
      indicating a role for this structure in the integration of photic and non-photic
      inputs related to the resetting of the biological clock. In the present study, we
      have used anterograde tracing from both eyes, bilateral eye enucleation, double
      immunofluorescence histochemistry, high-resolution confocal laser scanning
      microscopy and three-dimensional computer analysis to show that (1) PACAP
      containing RGCs project to the IGL and are the only source for the PACAP
      immunoreactive fibres in the IGL; (2) a few NPY-containing neurons in the IGL are
      innervated by PACAP-containing retinal nerve fibres and the contacts are both
      axodendritic and axosomatic; (3) most enkephalin-immunoreactive neurons in the
      IGL are innervated by PACAP-containing retinal afferents and the contacts are
      mainly axodendritic; (4) light stimulation at various time points activates (as
      evidenced by c-Fos induction) enkephalin-positive neurons but not NPY
      immunoreactive neurons. The findings suggest that PACAP-immunoreactive retinal
      afferents in the IGL primarily innervate enkephalin-immunoactive neurons and that
      the enkephalin-containing neurons, which project locally and to the contralateral
      IGL, are activated by light independent of diurnal time.

PMID- 17503088
TI  - Lipase-catalyzed esterification of conjugated linoleic acid with L-carnitine in
      solvent-free system and acetonitrile.
AB  - Lipase-catalyzed esterification of conjugated linoleic acid (CLA) with L
      carnitine in solvent-free system and acetonitrile was studied. Three lipases
      (Novzym 435, Amamo AY30 and Amano AYS) have been assayed as suitable biocatalysts
      in the reaction. It was found that Amano AY30 was the most effective biocatalyst
      in both solvent-free system and acetonitrile. The conversion rate varied from
      8.05 to 60.9% in terms of reaction conditions such as the amount of lipase, the
      presence of water, the amount of molecular sieves and reaction time. The
      conversions of substrate in solvent-free system were higher than that in
      acetonitrile. When the substrates were 1 mmol CLA and 1 mmol L-carnitine, the
      maximum conversion (60.9%) was obtained in solvent-free system with 150 mg lipase
      AY30, 50% water content and 150 mg molecular sieves at the reaction time of 24 h.
      A novel CLA ester product was successfully isolated and characterized by ESI-MS
      and (1)H NMR.

PMID- 17503089
TI  - Metabolic conditions of lactating Friesian cows during the hot season in the Po
      valley. 2. Blood minerals and acid-base chemistry.
AB  - In two consecutive summers, 21 and 18 cows respectively were monitored for acid
      base chemistry and some blood minerals, to assess their variation according to
      the level of heat stress at different stages of lactation. During both years, the
      cows were monitored according to their lactation phase (early, mid-, and late) at
      the beginning of the summer. Climatic conditions were described through the
      temperature humidity index. Cows were monitored weekly for: breathing rate,
      rectal temperature, hemogas parameters and blood minerals (morning and afternoon
      collection). In the first year, two hotter periods were identified, with more
      severe conditions in the second one, when cows had rectal temperatures higher
      than 40 degrees C. In the second year, only one hotter period was identified,
      with a heat stress comparable to that of the first period of the first year. The
      behaviour of rectal temperature, breathing rate and the parameters of the acid
      base status indicated that the suffering of the cows was on the borderline
      between mild and high heat stress during the hotter periods only, according to
      the climatic conditions in the two years. During the hotter periods, the acid
      base chemistry differed significantly with a reduction of HCO3- and an increase
      of Cl during the hotter hours of the day. The compensation mechanism for mild
      alkalosis during hotter hours maintained blood pH and the HCO3- returned to
      normal values during the night. Significant reductions were observed for Mg and
      Zn during the hotter periods. The cows in late lactation appeared to be less
      stressed by the hot climate.

PMID- 17503083
TI  - Microarray analysis of flax (Linum usitatissimum L.) stems identifies transcripts
      enriched in fibre-bearing phloem tissues.
AB  - To better understand the molecular processes associated with the development of
      the unusually long (> 30 mm) and strong bast fibre cells within the phloem of
      flax stems, we conducted a gene discovery experiment to identify transcripts
      enriched in fibre-bearing tissues, with the intention that these transcripts
      would serve as future targets for crop improvement and research in phloem
      development and cell wall deposition. We produced a library of 9,600 cDNA clones
      from the peels of flax stems, and selected tissue-specific cDNAs for sequencing
      based on two series of microarray experiments. In the first microarray series, we
      compared transcript abundance in stem-peels and leaves, and identified stem
      enriched transcripts putatively involved in the processes of polysaccharide and
      cell wall metabolism. In the second microarray series, we compared gene
      expression in three segments of the vertical stem axis, which constituted a
      developmental series for phloem fibres and other cell types. The expression of
      specific LTP and AGP transcripts was particularly well-correlated with stem
      segments during either the elongation phase or cell-wall thickening phase of
      phloem fibre development, and the phloem-specific enrichment of these transcripts
      was confirmed by qRT-PCR. Transcripts representing multiple, distinct chitinases,
      beta-galactosidases, arabinogalactan proteins (AGP), and lipid transfer proteins
      (LTPs) were among the interesting transcripts enriched in specific stages of the
      developing stem. Considered together, the results of our analyses suggest
      similarity between the molecular mechanisms underlying phloem fibre development
      and the gelatinous fibres of tension wood in trees.

PMID- 17503090
TI  - Effects of recent climate trends on the distribution of potential natural
      vegetation in Central Germany.
AB  - Introducing climate quotients for the growing season (Q(gs)) provides a way to
      quantify effects of climate trends with respect to Potential Natural Vegetation
      (PNV), especially beech forests (Fagus sylvatica L.) in Central Germany. What is
      crucial in this regard is the great influence of the dominant decrease in the
      amount of precipitation (up to 40% in the last 50 years) during the growing
      season versus the dormant season. However, precipitation during the dormant
      season (which is predominantly increasing: up to 40% in the last 50 years) is
      also important for replenishing the soil water supply. The Q(gs) values of the
      Climatic Normal period of 1971-2000 are generally higher (up to 12% in lowland
      areas) compared with the Climatic Normal period of 1961-1990, the extent of the
      difference being in general inversely proportional to elevation above sea level.
      What this means for the area under investigation is that humidity conditions,
      which generally improve as the elevation above sea level increases, have a
      positive effect on the site potential. However, a comparison of the
      climatologically important period of 1991-2003 with the period of 1961-1990 (area
      wide increase between 12% and 16%) could not identify this positive effect of
      elevation on precipitation for the area under investigation. With regard to the
      recent climate-based trends of PNV, we have shown that all natural spatial units
      in Central Germany are affected by progressing continentality (i.e., dryness)
      during the growing season and the resulting deterioration of the site potential.
      The area of potential beech forest at lower elevation has decreased in favour of
      oak forest as PNV, while less change is observed in the montane area.

PMID- 17503091
TI  - Ectomycorrhizal colonization of naturally regenerating Pinus sylvestris L.
      seedlings growing in different micro-habitats in boreal forest.
AB  - We investigated the species richness and composition of ectomycorrhizal (EM)
      fungi colonizing Pinus sylvestris L. seedlings naturally regenerating in boreal
      forest, in three different microhabitats: on forest ground, on decaying stumps,
      and within moss layer on erratic boulders. We tested the hypothesis that habitat
      differences would affect the composition of the EM community of regenerating pine
      seedlings. In total, 16 EM species were detected, from which none occurred on
      seedlings growing in all three microhabitats. Piloderma croceum and Cenococcum
      geophilum were common for seedlings growing in forest ground and on boulders,
      while Tricholoma aestuans and Suillus luteus were shared between seedlings
      growing on forest ground and decaying stumps. EM species richness and composition
      were strikingly different between seedlings regenerating in different
      microhabitats. Results are discussed as a function of dispersal and niche
      differentiation of EM fungi.

PMID- 17503092
TI  - The Cd(II)-binding abilities of recombinant Quercus suber metallothionein:
      bridging the gap between phytochelatins and metallothioneins.
AB  - In this work, we have analyzed both at stoichiometric and at conformational level
      the Cd(II)-binding features of a type 2 plant metallothionein (MT) (the cork oak,
      Quercus suber, QsMT). To this end four peptides, the wild-type QsMT and three
      constructs previously engineered to characterize its Zn(II)- and Cu(I)-binding
      behaviour, were heterologously produced in Escherichia coli cultures supplemented
      with Cd(II), and the corresponding complexes were purified up to homogeneity. The
      Cd(II)-binding ability of these recombinant peptides was determined through the
      chemical, spectroscopic and spectrometric characterization of the recovered
      clusters. Recombinant synthesis of the four QsMT peptides in cadmium-rich media
      rendered complexes with a higher metal content than those obtained from zinc
      supplemented cultures and, consequently, the recovered Cd(II) species are
      nonisostructural to those of Zn(II). Also of interest is the fact that three out
      of the four peptides yielded recombinant preparations that included S(2-)
      containing Cd(II) complexes as major species. Subsequently, the in vitro
      Zn(II)/Cd(II) replacement reactions were studied, as well as the in vitro acid
      denaturation and S(2-) renaturation reactions. Finally, the capacity of the four
      peptides for preventing cadmium deleterious effects in yeast cells was tested
      through complementation assays. Consideration of all the results enables us to
      suggest a hairpin folding model for this typical type 2 plant Cd(II)-MT complex,
      as well as a nonnegligible role of the spacer in the detoxification function of
      QsMT towards cadmium.

PMID- 17503093
TI  - Metallokinetic characteristics of antidiabetic bis(allixinato)oxovanadium(IV)
      related complexes in the blood of rat.
AB  - The antidiabetic effect of vanadium is a widely accepted phenomenon; some
      oxovanadium(IV) complexes have been found to normalize high blood glucose levels
      in both type 1 and type 2 diabetic animals. In light of the future clinical use
      of these complexes, the relationship among their chemical structures,
      physicochemical properties, metallokinetics, and antidiabetic activities must be
      closely investigated. Recently, we found that among bis(3
      hydroxypyronato)oxovanadium(IV) [VO(3hp)(2)] related complexes,
      bis(allixinato)oxovanadium(IV) [VO(alx)(2)] exhibits a relatively strong
      hypoglycemic effect in diabetic animals. Next, we examined its metallokinetics in
      the blood of rats that received five VO(3hp)(2)-related complexes by the blood
      circulation monitoring-electron paramagnetic resonance method. The metallokinetic
      parameters were obtained from the blood clearance curves based on a two
      compartment model; most parameters, such as area under the concentration curve
      and mean residence time, correlated significantly with the in vitro
      insulinomimetic activity in terms of 1/IC(50) (IC(50) is the 50% inhibitory
      concentration of the complex required for the release of free fatty acids in
      adipocytes) and the lipophilicity of the complex (log P (com)). The
      oxovanadium(IV) concentration was significantly higher and the species resided
      longer in the blood of rats that received VO(alx)(2) than in the blood of rats
      that received VO(3hp)(2) or bis(kojato)oxovanadium(IV); VO(alx)(2) also exhibited
      higher log P (com) and 1/IC(50) values. On the basis of these results, we propose
      that the introduction of lipophilic groups at the C2 and C6 positions of the 3hp
      ligand is an effective method to enhance the hypoglycemic effect of the
      complexes, as supported by the observed in vivo exposure and residence in the
      blood.

PMID- 17503094
TI  - A proteomic approach for the identification of bismuth-binding proteins in
      Helicobacter pylori.
AB  - Helicobacter pylori is a major human pathogen that can cause peptic ulcers and
      chronic gastritis. Bismuth-based triple or quadruple therapies are commonly
      recommended for the treatment of H. pylori infections. However, the molecular
      mechanisms underlying treatment with bismuth are currently not fully understood.
      We have conducted a detailed comparative proteomic analysis of H. pylori cells
      both before and after treatment with colloidal bismuth subcitrate (CBS). Eight
      proteins were found to be significantly upregulated or downregulated in the
      presence of CBS (20 microg mL(-1)). Bismuth-induced oxidative stress was
      confirmed by detecting higher levels of lipid hydroperoxide (approximately 1.8
      times) and hemin (approximately 3.4 times), in whole cell extracts of bismuth
      treated H. pylori cells, compared with those from untreated cells. The presence
      of bismuth also led to an approximately eightfold decrease in cellular protease
      activities. Using immobilized-bismuth affinity chromatography, we isolated and
      subsequently identified seven bismuth-binding proteins from H. pylori cell
      extracts. The intracellular levels of four of these proteins (HspA, HspB, NapA
      and TsaA) were influenced by the addition of CBS, which strongly suggests that
      they interact directly with bismuth. The other bismuth-interacting proteins
      identified were two enzymes (fumarase and the urease subunit UreB), and a
      translational factor (Ef-Tu). Our data suggest that the inhibition of proteases,
      modulation of cellular oxidative stress and interference with nickel homeostasis
      may be key processes underlying the molecular mechanism of bismuth's actions
      against H. pylori.

PMID- 17503095
TI  - Kinetics and mechanism of the reduction of (ImH)[trans-RuCl4(dmso)(Im)] by
      ascorbic acid in acidic aqueous solution.
AB  - A systematic study of the reduction of (ImH)[trans-RuCl(4)(dmso)(Im)] (NAMI-A;
      dmso is dimethyl sulfoxide, Im is imidazole), a promising antimetastasing agent
      entering phase II clinical trial, by L-ascorbic acid is reported. The rapid
      reduction of trans-[Ru(III)Cl(4)(dmso)(Im)](-) results in formation of trans
      [Ru(II)Cl(4)(dmso)(Im)](2-) in acidic medium (pH = 5.0) and is followed by
      successive dissociation of the chloride ligands, which cannot be suppressed even
      in the presence of a large excess of chloride ions. The reduction of NAMI-A
      strongly depends on pH and is accelerated on increasing the pH. Over the small pH
      range 4.9-5.1, the reaction is quite pH-independent and the influence of
      temperature and pressure on the reaction could be studied. On the basis of the
      reported activation parameters and other experimental data, it is suggested that
      the redox process follows an outer-sphere electron transfer mechanism. A small
      contribution from a parallel reaction ascribed to inner-sphere reduction of aqua
      derivatives of NAMI-A, was found to be favored by lower concentrations of the
      NAMI-A complex and higher temperature. In the absence of an excess of chloride
      ions, the reduction process is catalyzed by the Ru(II) products being formed. The
      reduction of NAMI-A is also catalyzed by Cu(II) ions and the apparent catalytic
      rate constant was found to be 1.5 x 10(6) M(-2) s(-1) at 25 degrees C.

PMID- 17503096
TI  - The structure of the Met144Leu mutant of copper nitrite reductase from
      Alcaligenes xylosoxidans provides the first glimpse of a protein-protein complex
      with azurin II.
AB  - Cu-containing nitrite reductases (NiRs) perform the reduction of nitrite to NO
      via an ordered mechanism in which the delivery of a proton and an electron to the
      catalytic type 2 Cu site is highly orchestrated. Electron transfer from a redox
      partner protein, azurin or pseudoazurin, to the type 1 Cu site is assumed to
      occur through the formation of a protein-protein complex. We report here a new
      crystal form in space group P2(1)2(1)2(1) of the Met144Leu mutant of NiR from
      Alcaligenes xylosoxidans (AxNiR), revealing a head-to-head packing motif
      involving residues around the hydrophobic patch of domain 1. Superposition of the
      structure of azurin II with that of domain 1 of one of the Met144Leu molecules
      provides the first glimpse of an azurin II-NiR protein-protein complex. Mutations
      of two of the residues of AxNiR, Trp138His (Barrett et al. in Biochemistry
      43:16311-16319, 2004) and Met87Leu, highlighted in the AxNiR-azurin complex,
      results in substantially decreased activity when azurin is used as the electron
      donor instead of methyl viologen, providing direct evidence for the importance of
      this region for complex formation.

PMID- 17503097
TI  - Locally enhanced sampling molecular dynamics study of the dioxygen transport in
      human cytoglobin.
AB  - Cytoglobin (Cyg)--a new member of the vertebrate heme globin family--is expressed
      in many tissues of the human body but its physiological role is still unclear. It
      may deliver oxygen under hypoxia, serve as a scavenger of reactive species or be
      involved in collagen synthesis. This protein is usually six-coordinated and binds
      oxygen by a displacement of the distal HisE7 imidazole. In this paper, the
      results of 60 ns molecular dynamics (MD) simulations of dioxygen diffusion inside
      Cyg matrix are discussed. In addition to a classical MD trajectory, an
      approximate Locally Enhanced Sampling (LES) method has been employed. Classical
      diffusion paths were carefully analyzed, five cavities in dynamical structures
      were determined and at least four distinct ligand exit paths were identified. The
      most probable exit/entry path is connected with a large tunnel present in Cyg.
      Several residues that are perhaps critical for kinetics of small gaseous
      diffusion were discovered. A comparison of gaseous ligand transport in Cyg and in
      the most studied heme protein myoglobin is presented. Implications of efficient
      oxygen transport found in Cyg to its possible physiological role are discussed.

PMID- 17503098
TI  - The cholesteryl ester transfer protein (CETP) gene and the risk of Alzheimer's
      disease.
AB  - Like the apolipoprotein E (APOE) gene, the most common genetic determinant for
      Alzheimer's disease (AD), the cholesteryl ester transfer protein (CETP) is
      involved in lipid metabolism. We studied the I405V polymorphism of the CETP gene
      in relation to AD. We genotyped 544 AD cases and 5,404 controls from the
      Rotterdam study, using a TaqMan allelic discrimination assay. Odds ratios (ORs)
      for AD were estimated using logistic regression analysis. CETP VV carriers showed
      significantly increased high-density lipoprotein levels compared to the IV and II
      carriers. In the overall analysis of AD, the risk of disease for the VV carriers
      of the CETP polymorphism was non-significantly increased compared to II carriers
      OR(VV) = 1.33, 95% confidence interval (CI) 0.96-1.90 p = 0.08). In those without
      the APOE*4 allele, the risk of AD for VV carriers was increased 1.67-fold (95% CI
      1.11-2.52, p = 0.01). The difference in the relationship between CETP and AD
      between APOE*4 carriers and APOE*4 non-carriers was statistically significant (p
      for interaction = 0.04). Our results suggest that the VV genotype of the I405V
      polymorphism of the CETP gene increases the risk of AD in the absence of the
      APOE*4 allele, probably through a cholesterol metabolism pathway in the brain.

PMID- 17503099
TI  - Risk factors for primary intracerebral hemorrhage in patients in Izumo City,
      Japan.
AB  - The annual incidence rate of primary intracerebral hemorrhage (ICH) in Izumo
      City, Japan, appears to be the highest rate among those reported. Despite
      improvement of management and surgical therapy, the overall morbidity and
      mortality after ICH are still high. The author investigated the risk factors for
      ICH in patients in Izumo. A case-control study of 242 patients (137 men and 105
      women with ages ranging from 34 to 97 years) with primary ICH was conducted in
      Izumo between 1991 and 1998. Hypertension, diabetes mellitus, heart disease,
      liver disease, alcohol consumption, cigarette smoking, and serum levels of total
      cholesterol, aspartate aminotransferase, and alanine aminotransferase were
      assessed as possible risk factors for ICH by using conditional logistic
      regression. The prevalence of hypertension among ICH patients was 77% and the
      odds ratio (OR) for hypertension was 17.07 (95% CI: 8.30-35.09), which are much
      higher than figures reported from Western countries. The OR for hypertension was
      higher in individuals < or = 69 years of age than in those > or = 70 years of age
      and lower for lobar hemorrhage than for hemorrhages at other sites. High serum
      total cholesterol (> or = 220 mg/dl) was the second most important risk factor
      for ICH (OR: 2.52; 95% CI: 1.23-5.14), and low total cholesterol (< 160 mg/dl)
      decreased the risk of ICH (OR: 0.47; 95% CI: 0.27-0.82). In contrast, heart
      disease decreased the risk of ICH, and there was no observed association between
      alcohol consumption, cigarette smoking, or diabetes mellitus and ICH. This study
      conducted in Izumo suggests that hypertension is the most important risk factor
      for ICH and contrary to most previous studies indicates that serum total
      cholesterol concentration is also positively associated with the risk of ICH. In
      contrast, heart disease may decrease the risk of ICH.

PMID- 17503100
TI  - The nicotinic acetylcholine receptor gene family of the nematode Caenorhabditis
      elegans: an update on nomenclature.
AB  - The simple nematode, Caenorhabditis elegans, possesses the most extensive known
      gene family of nicotinic acetylcholine receptor (nAChR)-like subunits. Whilst all
      show greatest similarity with nAChR subunits of both invertebrates and
      vertebrates, phylogenetic analysis suggests that just over half of these (32) may
      represent other members of the cys-loop ligand-gated ion channel superfamily. We
      have introduced a novel nomenclature system for these "Orphan" subunits,
      designating them as lgc genes (ligand-gated ion channels of the cys-loop
      superfamily), which can also be applied in future to unnamed and uncharacterised
      members of the cys-loop ligand-gated ion channel superfamily. We present here the
      resulting updated version of the C. elegans nAChR gene family and related ligand
      gated ion channel genes.

PMID- 17503101
TI  - Multimodal action representation in human left ventral premotor cortex.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate the neural
      systems responding to the sight and to the sound of an action. Subjects saw a
      video of paper tearing in silence (V), heard the sound of paper tearing (A), and
      saw and heard the action simultaneously (A + V). Compared to a non-action control
      stimulus, we found that hearing action sounds (A) activated the anterior inferior
      frontal gyrus and middle frontal gyrus in addition to primary auditory cortex.
      The anterior inferior frontal gyrus, which is known to be activated by
      environmental sounds, also seems to be involved in recognizing actions by sound.
      Consistent with previous research, seeing an action video (V) compared with
      seeing a non-action video activated the premotor cortex, intraparietal cortex,
      and the pars opercularis of the inferior frontal gyrus. An A + V facilitation
      effect was found in the ventral premotor cortex on the border of areas 44, 6, 3a,
      and 3b for the action stimuli but not for the control stimuli. This region may be
      involved in integrating multimodal information about actions. These data provide
      evidence that the ventral premotor cortex may provide an action representation
      that abstracts across both agency (self and other) and sensory modality (hearing
      and seeing). This function may be an important precursor of language functions.

PMID- 17503102
TI  - Effect of a 2 week CPAP treatment on mood states in patients with obstructive
      sleep apnea: a double-blind trial.
AB  - Obstructive sleep apnea (OSA) is a common disease with significant medical and
      psychiatric comorbidities. The literature documenting the effects of continuous
      positive airway pressure (CPAP) treatment on mood in OSA patients is mixed. We
      previously observed that 1 week of CPAP treatment did not result in improvements
      in mood beyond those observed in a group treated with placebo-CPAP. This study
      examined the effect of a 2 week CPAP treatment on mood in a placebo-controlled
      design in OSA patients. Fifty patients with untreated sleep apnea were evaluated
      by polysomnography and completed the Profile of Mood States (POMS) pre-/post
      treatment. The patients were randomized for 2 weeks to either therapeutic CPAP or
      placebo-CPAP (at insufficient pressure). Both the therapeutic CPAP and the
      placebo-CPAP groups showed significant improvements in POMS total score, tension,
      fatigue, and confusion. No significant time x treatment effect was observed for
      either group. We could not show a specific beneficial impact of CPAP treatment on
      mood in OSA patients.

PMID- 17503103
TI  - Angiotensin receptor blockers on the formularies of Medicare drug plans.
AB  - BACKGROUND: The presence of angiotensin receptor blockers (ARBs) on the
      formularies of Medicare Part D prescription drug plans (PDPs) is vitally
      important to the health of seniors who cannot tolerate angiotensin-converting
      enzyme (ACE) inhibitors. OBJECTIVE: To determine whether ARBs are present on the
      formularies of PDPs and how the prescription cost-sharing for ARBs under Part D
      compares to cost-sharing before Part D. DESIGN/PARTICIPANTS: Cross-sectional
      analyses of March 2006 Medicare Part D formularies (n = 1,446) and of ARB
      utilization and cost-sharing for adults over the age of 64 included in the
      nationally representative Medical Expenditure Panel Survey. MAIN OUTCOME
      MEASURES: (1) Presence of ARBs on Part D formularies. (2) Average out-of-pocket
      costs for 30-day supply of ARBs before and after Part D (both in 2006 dollars).
      RESULTS: All PDP formularies included at least 1 ARB. Most plans covered 2 ARBs
      (41%) and 35% covered all 7. The average monthly copay for the most commonly used
      ARB, valsartan, is $28 under part D, $14 before Part D for individuals with
      prescription coverage, and $53 before Part D for individuals without coverage.
      CONCLUSIONS: Whereas ARBs are present on all Part D formularies, many seniors
      will pay more for these drugs under Part D. Any savings in copayments under Part
      D may be erased by the monthly premium and by more expensive cost-sharing when
      seniors reach the 'donut hole'.

PMID- 17503104
TI  - Prevalence of depression-PTSD comorbidity: implications for clinical practice
      guidelines and primary care-based interventions.
AB  - BACKGROUND: Compared to those with depression alone, depressed patients with
      posttraumatic stress disorder (PTSD) experience more severe psychiatric
      symptomatology and factors that complicate treatment. OBJECTIVE: To estimate PTSD
      prevalence among depressed military veteran primary care patients and compare
      demographic/illness characteristics of PTSD screen-positive depressed patients
      (MDD-PTSD+) to those with depression alone (MDD). DESIGN: Cross-sectional
      comparison of MDD patients versus MDD-PTSD+ patients. PARTICIPANTS: Six hundred
      seventy-seven randomly sampled depressed patients with at least 1 primary care
      visit in the previous 12 months. Participants composed the baseline sample of a
      group randomized trial of collaborative care for depression in 10 VA primary care
      practices in 5 states. MEASUREMENTS: The Patient Health Questionnaire-9 assessed
      MDD. Probable PTSD was defined as a Primary Care PTSD Screen > or = 3. Regression
      based techniques compared MDD and MDD-PTSD+ patients on demographic/illness
      characteristics. RESULTS: Thirty-six percent of depressed patients screened
      positive for PTSD. Adjusting for sociodemographic differences and physical
      illness comorbidity, MDD-PTSD+ patients reported more severe depression (P <
      .001), lower social support (P < .001), more frequent outpatient health care
      visits (P < .001), and were more likely to report suicidal ideation (P < .001)
      than MDD patients. No differences were observed in alcohol consumption, self
      reported general health, and physical illness comorbidity. CONCLUSIONS: PTSD is
      more common among depressed primary care patients than previously thought.
      Comorbid PTSD among depressed patients is associated with increased illness
      burden, poorer prognosis, and delayed response to depression treatment. Providers
      should consider recommending psychotherapeutic interventions for depressed
      patients with PTSD.

PMID- 17503105
TI  - PTSD in urban primary care: high prevalence and low physician recognition.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with medical and
      psychological morbidity. The prevalence of PTSD in urban primary care has not
      been well described. OBJECTIVE: To measure the prevalence of PTSD in primary care
      patients overall and among those with selected conditions (chronic pain,
      depression, anxiety, heavy drinking, substance dependence (SD), irritable bowel
      syndrome (IBS), and immigrant status). DESIGN: Cross-sectional study.
      PARTICIPANTS: English-speaking patients aged 18-65 years old, awaiting primary
      care appointments in an urban academic medical center, were eligible for
      enrollment to determine PTSD prevalence (N = 509). Additional eligible
      participants (n = 98) with IBS or SD were subsequently enrolled. MEASUREMENTS:
      PTSD (past year) and trauma exposure were measured with Composite International
      Diagnostic Interview. We calculated the prevalence of PTSD associated with
      depression, anxiety, heavy drinking, SD, IBS, and chronic pain. Only the analyses
      on heavy drinking, SD, and IBS used all 607 participants. RESULTS: Among the 509
      adults in primary care, 23% (95% CI, 19-26%) had PTSD, of whom 11% had it noted
      in the medical record. The prevalence of PTSD, adjusted for age, gender, race,
      and marital and socioeconomic statuses, was higher in participants with, compared
      to those without, the following conditions: chronic pain (23 vs 12%, p = .003),
      major depression (35 vs 11%, p < .0001), anxiety disorders (42 vs 14%, p <
      .0001), and IBS (34 vs 18%, p = .01) and lower in immigrants (13 vs 21%, p =
      .05). CONCLUSIONS: The prevalence of PTSD in the urban primary care setting, and
      particularly among certain high-risk conditions, compels a critical examination
      of optimal approaches for screening, intervention, and referral to PTSD
      treatment.

PMID- 17503106
TI  - Decreased awareness of current smoking among health care providers of HIV
      positive compared to HIV-negative veterans.
AB  - BACKGROUND: Cigarette smoking is an important risk factor for morbidity and
      mortality in HIV-positive patients on combination antiretroviral therapy.
      OBJECTIVE: To determine whether awareness of smoking differs between HIV and non
      HIV providers, and to identify factors associated with failure to recognize
      current smoking. DESIGN: Observational study. PARTICIPANTS: 801 HIV-positive and
      602 HIV-negative patients, 72 HIV and 71 non-HIV providers enrolled in the
      Veterans Aging Cohort 5 Site Study. MEASUREMENTS: Data sources included patient
      and provider questionnaires; electronic medical records; and the national
      administrative VA database. We calculated sensitivity, specificity, and measures
      of agreement between patient- and provider-reported smoking, and examined factors
      associated with failure to recognize current smoking using logistic regression.
      RESULTS: Whereas most providers were correct when they identified a patient as a
      current smoker (specificity > or = 90%), HIV providers missed current smoking
      more often (sensitivity 65% for HIV vs. 82% for non-HIV). Kappa scores for
      current smoking were significantly lower for HIV compared to non-HIV providers
      (0.55 vs. 0.75, p < .001). In models adjusted for age, gender, race, and other
      differences, patient HIV status and provider specialty in infectious diseases
      were independent predictors of a provider's failure to recognize current smoking.
      Comorbid illnesses, cough/dyspnea, degree of immune competence and HIV viral
      suppression did not impact recognition of current smoking. Only 39% of HIV
      providers reported confidence in their ability to influence smoking cessation
      compared to 62% of non-HIV providers (p = .049). CONCLUSIONS: Interventions to
      increase HIV provider awareness of current smoking and skills to influence
      smoking cessation are needed. Efforts should also target patient populations with
      smoking-related comorbid diseases who would especially benefit from smoking
      cessation.

PMID- 17503107
TI  - Feeling bad in more ways than one: comorbidity patterns of medically unexplained
      and psychiatric conditions.
AB  - BACKGROUND: Considerable overlap in symptoms and disease comorbidity has been
      noted among medically unexplained and psychiatric conditions seen in the primary
      care setting, such as chronic fatigue syndrome, low back pain, irritable bowel
      syndrome, chronic tension headache, fibromyalgia, temporomandibular joint
      disorder, major depression, panic attacks, and posttraumatic stress disorder.
      OBJECTIVE: To examine interrelationships among these 9 conditions. DESIGN: Using
      data from a cross-sectional survey, we described associations and used latent
      class analysis to investigate complex interrelationships. PARTICIPANTS: 3,982
      twins from the University of Washington Twin Registry. MEASUREMENTS: Twins self
      reported a doctor's diagnosis of the conditions. RESULTS: Comorbidity among these
      9 conditions far exceeded chance expectations; 31 of 36 associations were
      significant. Latent class analysis yielded a 4-class solution. Class I (2%
      prevalence) had high frequencies of each of the 9 conditions. Class II (8%
      prevalence) had high proportions of multiple psychiatric diagnoses. Class III
      (17% prevalence) participants reported high proportions of depression, low back
      pain, and headache. Participants in class IV (73% prevalence) were generally
      healthy. Class I participants had the poorest markers of health status.
      CONCLUSIONS: These results support theories suggesting that medically unexplained
      conditions share a common etiology. Understanding patterns of comorbidity can
      help clinicians care for challenging patients.

PMID- 17503108
TI  - Awareness of hepatitis C diagnosis is associated with less alcohol use among
      persons co-infected with HIV.
AB  - BACKGROUND AND OBJECTIVE: It is unknown whether testing HIV-infected individuals
      for hepatitis C virus (HCV) and informing them of their HCV status impacts
      subsequent alcohol use. We hypothesized that HIV-infected individuals with
      current or past alcohol problems who reported being told they had HCV were more
      likely to 1) abstain from alcohol and 2) not drink unhealthy amounts compared to
      individuals who had not been told. DESIGN, PARTICIPANTS, AND MEASUREMENTS: Data
      from a prospective, observational cohort study (HIV-Longitudinal
      Interrelationships of Viruses and Ethanol) were used to assess the association
      between awareness of having HCV at baseline and subsequent abstinence and not
      drinking unhealthy amounts as reported at 6-month follow-up intervals. General
      estimating equations logistic regression was used to account for the correlation
      from using repeated observations from the same subject over time. We adjusted for
      age, sex, race, homelessness, injection drug use, depressive symptoms, and having
      abnormal liver tests. RESULTS: Participants who reported being told they had HCV
      were more likely to report abstaining from alcohol (AOR = 1.60; 95% CI: 1.13 to
      2.27) and not drinking unhealthy amounts (AOR = 1.46; 95% CI: 1.01 to 2.11).
      CONCLUSIONS: Among patients infected with HIV who had a history of alcohol
      problems, reporting being told one had HCV was associated with greater abstinence
      from alcohol and less unhealthy amounts of drinking.

PMID- 17503109
TI  - A captive audience: a pilot study of screening and counseling hospitalized women
      for fracture risk.
AB  - BACKGROUND: Innovative methods are needed to improve screening for osteoporosis,
      especially in women with multiple comorbid conditions. OBJECTIVES: Determine
      whether a fracture risk-screening program including a bedside calcaneal
      ultrasound is feasible in hospitalized women, and determine whether
      identification of fracture risks results in behavior change after discharge.
      DESIGN: Prospective uncontrolled feasibility study. SETTING: Five hundred twenty
      eight bed academic hospital. PARTICIPANTS: One hundred three hospitalized women
      age 60 years or older. METHODS: A bedside calcaneal ultrasound was used to
      estimate bone mineral density. Clinical fracture risks were obtained via
      interview. The patient and primary care physician received personalized risk
      information and educational material. RESULTS: Of 103 eligible women, 59 (57%)
      agreed to undergo bedside screening and counseling. Of these 59 women, 49 (83%)
      had at least one major clinical risk factor for fracture. The median T-score was 
      2.5. Among the 42 women available for phone follow-up 2 months after hospital
      discharge, 34 (81%) reported after at least 1 recommendation to diminish fracture
      risk. CONCLUSION: A hospital-based osteoporosis screening program using calcaneal
      ultrasound is feasible and identifies women at risk of fracture. Feedback of low
      bone mineral density and fracture risk during hospitalization may promote
      behavior change to diminish fracture risk after discharge.

PMID- 17503110
TI  - Association between length of residence and cardiovascular disease risk factors
      among an ethnically diverse group of United States immigrants.
AB  - BACKGROUND: Although differences in cardiovascular disease (CVD) risk factors
      between immigrants and nonimmigrants have been examined previously, the effect of
      acculturation on CVD risk factors in immigrants has been less well studied.
      OBJECTIVE: To determine the association between length of U.S. residence (proxy
      for acculturation) and major CVD risk factors. METHODS: Data on 5,230 immigrant
      adults from the 2002 National Health Interview Survey (NHIS) was analyzed.
      Primary independent variable was length of U.S. residence < 10, 10 to < 15, and >
      or = 15 years. Main outcome measures included obesity, hypertension, diabetes,
      hyperlipidemia, smoking, and physical inactivity. Multiple logistic regression
      was used to assess the association between length of residence and odds of
      multiple CVD risk factors adjusting for confounders. SAS-callable SUDAAN was used
      for statistical analysis. RESULTS: Among the patients, 55.4% were obese, 17.3%
      had hypertension, 15.9% had hyperlipidemia, 6.6% had diabetes, 79.3% were
      physically inactive, and 14.3% were smokers. Using < 10 years as reference, those
      with length of residence > or = 15 years were more likely to be obese (OR 1.31,
      95% CI 1.03-1.65), have hyperlipidemia (OR 1.59, 95% CI 1.14-2.22), and be
      smokers (OR 1.39, 95% CI 1.04-1.85). Length of residence > or = 15 years was
      associated with decreased odds of sedentary lifestyle (OR 0.63, 95% CI 0.47
      0.84). Length of residence > or = 15 years was not associated with odds of having
      diabetes (OR 1.40, 95% CI 0.78-2.51) or hypertension (OR 1.21, 95% CI 0.86-1.71).
      CONCLUSIONS: Among immigrants from diverse ethnic backgrounds, longer length of
      residence in the United States is associated with increased odds of obesity,
      hyperlipidemia, and cigarette smoking even after adjusting for relevant
      confounding factors.

PMID- 17503111
TI  - Reducing racial bias among health care providers: lessons from social-cognitive
      psychology.
AB  - The paper sets forth a set of evidence-based recommendations for interventions to
      combat unintentional bias among health care providers, drawing upon theory and
      research in social cognitive psychology. Our primary aim is to provide a
      framework that outlines strategies and skills, which can be taught to medical
      trainees and practicing physicians, to prevent unconscious racial attitudes and
      stereotypes from negatively influencing the course and outcomes of clinical
      encounters. These strategies and skills are designed to: 1) enhance internal
      motivation to reduce bias, while avoiding external pressure; 2) increase
      understanding about the psychological basis of bias; 3) enhance providers'
      confidence in their ability to successfully interact with socially dissimilar
      patients; 4) enhance emotional regulation skills; and 5) improve the ability to
      build partnerships with patients. We emphasize the need for programs to provide a
      nonthreatening environment in which to practice new skills and the need to avoid
      making providers ashamed of having racial, ethnic, or cultural stereotypes. These
      recommendations are also intended to provide a springboard for research on
      interventions to reduce unintentional racial bias in health care.

PMID- 17503112
TI  - Convulsive status epilepticus after ischemic stroke and intracerebral hemorrhage:
      frequency, predictors, and impact on outcome in a large administrative dataset.
AB  - OBJECTIVE: Relatively little is known about the epidemiology of generalized
      convulsive status epilepticus (GCSE) in acute ischemic and hemorrhagic stroke. We
      examined the occurrence of GCSE in acute ischemic stroke (AIS) and intracerebral
      hemorrhage (ICH) using a large discharge database. METHODS: Data were derived
      from the Nationwide Inpatient Sample for the years 1994-2002. Using the
      appropriate ICD-9-CM codes, patients admitted through the emergency room with a
      diagnosis of AIS or ICH were selected for analysis. From these patients, those
      coded as having GCSE were identified. Multivariate logistic regression was
      performed using clinical elements available in the database to identify
      independent predictors of GCSE. The association between GCSE and various outcome
      measures was also assessed. RESULTS: The cohort included 718,531 hospitalizations
      with AIS and 102,763 with ICH. GCSE developed in 1,415 (0.2%) of the AIS cohort
      and 266 (0.3%) of the ICH cohort. For the AIS cohort, female sex, African
      American race, renal disease, alcohol abuse, sodium imbalance, and hemorrhagic
      transformation were associated with higher rates, while increasing age,
      hypertension, and diabetes mellitus were associated with lower rates of GCSE. For
      the ICH cohort, African American and Hispanic race, renal disease, coagulopathy,
      brain tumor, alcohol abuse, and sodium imbalance were associated with higher
      rates, while increasing age and hypertension were associated with lower rates of
      GCSE. GCSE was associated with higher rates of adverse outcomes. CONCLUSIONS:
      GCSE is a rare but serious complication in the setting of acute ischemic stroke
      and intracerebral hemorrhage.

PMID- 17503114
TI  - Risk predictors and frequency of cardiovascular symptoms occurring during cardiac
      rehabilitation programs in phase III-WHO.
AB  - INTRODUCTION: Rehabilitation in ambulatory heart groups has become a well
      established part of comprehensive cardiac treatment in Germany. Identifying
      patients at risk for cardiovascular symptoms is important for the efficiency and
      safety of the program. METHODS: Questionnaires were mailed to ambulatory heart
      groups in the state of Hessen, Germany, and returned by 1935/13 174 (15%)
      patients, age 65.9 +/- 7.6 years, 1504/1935 (77.7%) males, comprising
      approximately 674 000 patient exercise hours. RESULTS: 828 symptoms were reported
      by 538 patients, comprising dyspnea in 330/538 (61.3%), angina pectoris in 80/538
      (14.9%), palpitation in 145/538 (27%), tachycardia in 59/538 (11%), dizziness in
      152/538 (28.3%), fainting in 6/538 (1.1%), and others in 47/538 (8.7%).
      Cardiovascular symptoms occurred more frequently in patients presenting with
      overexertion (43/68 (63.2%), p < 0.0001, RR 4.77 [95% CI 3.01-7.56]), chronic
      heart failure (115/291 (39.5%) vs 419/1624 (25.8%), p < 0.0001, RR 1.88 [95% CI
      1.45-2.43]), lower exercise capacity (1.49 +/- 0.4 vs 1.59 +/- 0.5 W/kg body
      weight, p = 0.0002, mean difference -0.096 [95% CI (-0.146) -(-0.046)]),
      hypertension (269/ 854 (31.5%) vs 266/1068 (24.9%), p = 0.001, RR 1.39 [95% CI
      1.14-1.69]), and hyperlipidemia (280/ 907 (30.9%) vs 255/1015 (25.1%), p = 0.005,
      RR 1.33 [95% CI 1.09-1.63]). Cardiovascular symptoms were more frequent in women
      (141/431(32.7%) vs 397/1503 (26.4%), p = 0.01, RR 1.35 [95% CI 1.08-1.71]).
      Overexertion (p < 0.0001), heart failure (p = 0.003), and hypertension (p = 0.05)
      are significant independent predictors of cardiovascular symptoms, while female
      gender (p = 0.06), and hyperlipidemia (p = 0.07) are not as significant. Previous
      myocardial infarction and diabetes had no statistical significant impact on
      cardiovascular symptoms. CONCLUSION: Patients likely to experience cardiovascular
      symptoms in ambulatory rehabilitation can be identified by their medical history
      and perceived exertion.

PMID- 17503115
TI  - Cognitive and neuropsychological disorders in neuroimmunological diseases.

PMID- 17503113
TI  - Autoimmunological features in inflammatory cardiomyopathy.
AB  - During recent years, increasing evidence has been obtained that cellular as well
      as humoral autoimmunity is involved in the pathogenesis of dilated cardiomyopathy
      (DCM). The immune system is generally activated by viral infections with the
      objective of virus elimination from the myocardium. However, a relevant number of
      patients demonstrate viral persistence and/or chronic inflammation in the
      myocardium. This chronic myocardial inflammation, defined by chronic
      inflammation, is termed "inflammatory cardiomyopathy" according to the WHO
      classification of cardiomyopathies. Chronic inflammation is frequently followed
      by the development of autoimmunity. A breakdown in the control mechanisms
      protecting against autoimmune reactions by both presentation of normally not
      accessible self-antigens and bystander- activation, induced by the pathogen,
      leads to the formation of autoreactive antibodies and T cells. The auto-reactive
      antibodies interact directly with heart tissue resulting in altered signal
      transduction or complement activation, whereas the T cell-mediated mechanisms
      include direct attack by cytotoxic T cells or indirect effects of cytotoxic
      cytokines released by stimulated T cells or macrophages.

PMID- 17503116
TI  - Fatigue in neuroimmunological diseases.
AB  - Fatigue is a widespread symptom in numerous neuroimmunological diseases like
      multiple sclerosis (MS), myasthenia gravis, morbus Behcet, neurosarcoidosis,
      neuroborreliosis or immune vasculitis. This phenomenon is best investigated in
      MS. The complex mechanisms underlying fatigue in MS are still poorly understood;
      alterations in immune system activation, central nervous system dysregulation,
      impaired nerve conduction, and neuroendocrine dysregulation have to be
      considered. These immune and neural mechanisms may cause the initial symptoms of
      fatigue; however, the fatigue symptom may be exacerbated by secondary overlapping
      factors (e. g. depressive mood, sleep disturbances, unhealthy life style) which
      are likely associated with the feeling of fatigue. Wessely conceptualised four
      components of fatigue: behaviour (effects of fatigue), feeling (subjective
      experience), mechanisms, and context (e. g. environment, attitudes). So far most
      examinations have dealt with the first or the second component of the
      multidimensional construct fatigue, either concentrating on the behavioural
      aspect in the physical or in the cognitive sphere or on the subjective aspect.
      The Rostock Fatigue Study investigated two of the components: objective
      performance and subjective fatigue estimation in the cognitive and in the
      physical sphere. MS patients showed a reversed relationship between below-average
      objective performance in the cognitive and in the physical sphere and high
      subjective feeling of tiredness when compared to healthy individuals. The
      clinical management of fatigue should include an assessment of the various
      factors that can cause fatigue as well as a step-wise treatment approach that
      encompasses nonpharmacological approaches and pharmacological interventions.

PMID- 17503117
TI  - Coping with neuroimmunological diseases.
AB  - Although there is little doubt about a considerable need for psychosocial support
      in patients with severe neuroimmunological diseases, the theoretical elaboration
      of stressful illness consequences as well as the development of standardised
      intervention programs are still in their beginnings. In the present paper, models
      of coping with chronic illness are characterised as a suitable framework. After a
      short overview of psychological dimensions of physical illness, concepts from the
      coping literature that seem to meet these demands are briefly introduced.
      Furthermore, recent results of coping research especially in multiple sclerosis
      (MS) are outlined in an overview which also includes findings from evaluation
      studies. Moreover, aims and techniques, which constitute necessary elements of
      coping skills training for patients with neuroimmunological disease, are
      described. Questions of suitability of coping interventions for subgroups of
      patients with multiple sclerosis are finally discussed.

PMID- 17503118
TI  - Complementary and alternative medicine and coping in neuroimmunological diseases.
AB  - The utilisation of complementary and alternative medicine (CAM) is widespread in
      neuroimmunological diseases like multiple sclerosis (MS) but has been disregarded
      in research until lately. After describing the problems of definition in CAM,
      different categories will be described. Various confounding factors on CAM
      utilisation exist, though hardly investigated. Besides sociodemographic variables
      like education, income, gender and age, illness-related factors like severity of
      disease are discussed. Furthermore, the important role of coping and CAM
      utilisation has not been investigated in neuroimmunological diseases, yet.
      Results derived from our investigations on CAM utilisation in MS indicate that
      users of CAM apply coping strategies, such as "rumination", "search for
      information" and "search for meaning in religion", more frequently than non-users
      and that current CAM utilisation is related to depression. Further research is
      needed in this field, as well as in other neuroimmunological diseases.

PMID- 17503119
TI  - Shared decision making and self-management in multiple sclerosis--a consequence
      of evidence.
AB  - Shared decision making is increasingly recognised as the ideal model of patient
      physician communication especially in chronic diseases with partially effective
      treatments such as multiple sclerosis (MS). Since 2001, we studied prerequisites
      for patient participation in decision making as well as the effects of evidence
      based patient information on decision making processes in MS. In pre-studies we
      found that 80% of MS patients demand autonomous roles in treatment decisions
      which contrasts to a poor knowledge of risks. On the other hand MS patients are
      not disturbed by evidence-based, balanced complex information. MS patients can
      understand this kind of information and are able to transfer new abilities to
      other situations. Major information interests were related to symptom
      alleviation, diagnostic procedures and prognosis. Currently, we study the effects
      of a 4 hour education programme on relapse management versus an information
      leaflet as controls in 150 RR MS patients in a randomised-controlled trial. In a
      second trial including 280 MS patients we study the effects of an evidence-based
      decision aid on immunotherapy on decisional role preference and performance in
      the patient physician encounter. Results at the end of 2006 will show to which
      extent patient education with a focus on evidence-based patient information
      influences participation in the decision making process. Assuming that patient
      education programmes will enhance self-management abilities and the sense of
      control over the disease with enhanced quality of life and well-being, further
      modules covering all aspects of MS are to be developed.

PMID- 17503120
TI  - Neuropsychological assessment.
AB  - Neuropsychological assessment is one of the main fields of activity of clinical
      neuropsychologists. Goals of this assessment are verification and description of
      cognitive and affective impairments as the consequence of brain damage. Included
      are examinations of basal and higher sensory functions, the intellectual profile,
      memory, attention and sensorimotor functions, executive functions, specific
      education- and profession-related skills as well as affectivity and emotional
      functions. Diagnostic assignment encompasses the description of the current
      status, follow-up examinations, experts' reports, planning of rehabilitation
      measures but also the uncovering of dysfunctions after brain damage that are
      morphologically not yet verifiable. Referring to the respective diagnostic
      question, assessment has to be planned thoroughly including results of prior
      examinations, exploration and anamnesis, also taking into account factors which
      might hamper test administration or which otherwise might affect the results. The
      assessment also includes monitoring of behaviour and the registration of
      tendencies for aggravation or simulation. Analysis and interpretation of the
      results both refer to the diagnostic question and to the hypotheses developed at
      the beginning of the examination. Results and conclusions derived from the
      examination are documented in reports of diagnostic findings or in experts'
      reports.

PMID- 17503121
TI  - Cortical, subcortical and spinal alterations in neuroimmunological diseases.
AB  - Inflammatory and immune mediated diseases of the nervous system are reflected by
      a broad spectrum of different clinical deficits. The reason for this is that
      inflammation may affect any part of the nervous system. Nevertheless, certain
      regions in the brain and spinal cord are more frequently affected than others.
      The topographical distribution of inflammatory lesions in the nervous system
      depends upon a large variety of different factors, which are different in the
      various infectious and autoimmune diseases. Aim of this short review is to
      discuss the main factors determining lesional topography in brain inflammation
      and to illustrate these patterns of tissue injury with clinical examples.

PMID- 17503122
TI  - Cognitive dysfunctions in multiple sclerosis--a "multiple disconnection
      syndrome"?
AB  - After giving a brief overview of the cognitive core deficit in multiple sclerosis
      (MS), pros and cons of considering the clinical characteristics as a form of
      'subcortical dementia' are discussed. By comparing the neuropsychological
      descriptions of MS patients as given in the literature to other neurological
      diseases which are also associated with neuropsychological deficiencies, we
      propose the term 'multiple disconnection syndrome' to describe the variety of
      neuropsychological deficits encountered in MS.

PMID- 17503123
TI  - Immunology and neurology.
AB  - The classical field of neuroimmunology deals with the immune response in
      infectious, autoimmune-mediated, ischemic, degenerative, traumatic, and
      neoplastic diseases of the nervous system with a major focus on immune-mediated
      demyelination. Recently more and more evidence points to a broader interaction
      between the immune and nervous systems via morphological connections, shared
      signal molecules and common mechanisms of signal transduction. Consequently,
      immune processes affect nervous functions and vice versa under both physiologic
      and pathologic conditions. This includes neuroendocrine (hormonal) and vegetative
      (neurotransmitter-mediated) influences on the immune response including
      conditioned immunostimulation and immunosuppression (neuroimmunomodulation) as
      well as effects of immune mediators (cytokines) on neuronal and psychic functions
      (psychoneuroimmunology). These findings have a strong impact on future strategies
      for the treatment of somatic as well as psychiatric diseases.

PMID- 17503124
TI  - Reliability and validity of neuropsychological screening and assessment
      strategies in MS.
AB  - Neuropsychological impairment is common in MS but routine evaluation is
      cumbersome. Many proposed avenues to more cost effective evaluation of cognition
      in MS have appeared in the literature. In this article, we summarize work
      conducted at our center over the past five years involving two specific
      evaluation methods, the Multiple Sclerosis Neuropsychological Screening
      Questionnaire (MSNQ) designed to screen for neuropsychological impairment in MS
      and the Minimal Assessment of Cognitive Function in MS (MACFIMS) designed to
      quantify cognitive function with psychometric testing. Our research shows that
      these methods are reliable and valid. Data show strong relationships with
      neuropsychiatric features of the disease, brain imaging and vocational outcomes.
      Work with new non-conventional brain imaging techniques and finer analysis of
      reliability during serial testing protocols is underway.

PMID- 17503125
TI  - Cognitive screening in multiple sclerosis.
AB  - Cognitive screening tests in multiple sclerosis (MS) are time- and cost-saving
      test instruments. In the case of a positive test result (alert function) a
      comprehensive cognitive test procedure should be administered. This paper
      explains what cognitive screening in MS means and presents several screening
      instruments used in MS with their statistical test characteristics, e. g.
      sensitivity and specificity.

PMID- 17503126
TI  - Diagnostics of cognitive dysfunctions in multiple sclerosis.
AB  - Cognitive dysfunctions are frequent symptoms in multiple sclerosis (MS). Up to
      65% of MS patients suffer from cognitive dysfunctions. Especially memory,
      attention and executive functions are impaired. These problems strongly affect
      the patients' ability to work and their quality of life (QoL). A differentiating
      diagnostic effort is necessary to control fatigue and depression. Screening tools
      alone can not provide a detailed description of all cognitive domains. Therefore,
      an elaborated neuropsychological diagnostics is necessary. This report provides a
      description of cognitive functions and its diagnostic opportunities, especially
      in MS patients. After displaying aspects of differential diagnostics, a
      recommendation for a diagnostic work schedule is given.

PMID- 17503127
TI  - Cognitive impairment in multiple sclerosis.
AB  - Cognitive dysfunctions are frequent symptoms of multiple sclerosis (MS) and occur
      in up to 65% of patients. Especially memory, attention, executive and visual
      constructive functions are impaired. These problems strongly affect patients'
      ability to work, social relationships, and quality of life. Symptoms of physical
      disabilities can arise independently. Cognitive dysfunctions are clear indicators
      of MS progression, because they represent highly complex functions that depend on
      the integrity of the neuronal networks. Once manifested after a relapse, they
      remain stable . Given a differentiating diagnosis, it is possible to treat these
      dysfunctions by cognitive training and with pharmaceutical drugs, for example by
      immunomodulating drugs. However, treatment options are limited at present. This
      report provides a detailed description of cognitive functions and performance in
      MS patients, their comorbidities such as fatigue and depression and therapeutic
      options.

PMID- 17503128
TI  - Brain atrophy and cognitive impairment in multiple sclerosis: a review.
AB  - Multiple sclerosis (MS) is a common neurological disease in the Western
      hemisphere that leads to neurological dysfunctions and frequently from its onset
      to cognitive impairment, which together predict quality of life. Recent
      pathological and imaging studies have focused on brain atrophy representing
      axonal injury and loss as being crucial for developing disability and
      neuropsychological impairment. Brain atrophy has therefore been proposed to be a
      tool for monitoring disease progress. Here, we review the possible origins of
      brain atrophy and its correlation with cognitive impairment in MS.

PMID- 17503129
TI  - Transcranial brain sonography findings related to neuropsychological impairment
      in multiple sclerosis.
AB  - Cognitive dysfunction, fatigue and mood disorder contribute to the
      neuropsychological impairment that is common in multiple sclerosis (MS). The
      present paper reviews application of transcranial brain sonography (TCS) in MS
      patients and TCS findings related to neuropsychological dysfunction. TCS is a new
      neuroimaging method displaying tissue echogenicity of the brain through the
      intact skull. Whereas the cortex can not be discriminated from the subcortical
      white matter with TCS, subcortical brain structures such as ventricles and basal
      ganglia can be adequately displayed. Even though TCS proved sensitive and
      reliable in measuring widths of third and lateral ventricles in a number of
      neurodegenerative diseases, relatively few TCS studies on MS patients have been
      reported. Data of these studies suggest a good correlation of cognitive
      dysfunction and width of third ventricle which can be measured reliably with TCS.
      Moreover, abnormal TCS findings of basal ganglia were associated with cognitive
      impairment. However, TCS findings of midbrain structures, basal ganglia and
      ventricles did not correlate with fatigue or depression in MS patients. TCS has
      the advantages of low costs, short investigation times and unlimited
      repeatability. The use of third-ventricle and basalganglia TCS for predicting and
      monitoring neuropsychological impairment in MS patients, however, needs to be
      elucidated in further studies.

PMID- 17503130
TI  - Relation between functional brain imaging, cognitive impairment and cognitive
      rehabilitation in patients with multiple sclerosis.
AB  - Cognitive impairment belongs to the core symptoms in MS affecting quality of
      life, self-esteem, and social as well as occupational functioning. Due to this
      high impact on patients' well-being efficient treatment concepts are required.
      Imaging studies on cognition have shown that functional reorganisation takes
      place spontaneously to compensate for deficits. In mildly to moderately impaired
      patients these processes may support coping with emerging deficits. However,
      these compensatory processes seem to be limited as brain activation of
      cognitively severely impaired patients is characterised by decreased additional
      recruitment of brain regions. Cognitive rehabilitation concentrates on the
      question whether induction of brain plasticity is possible for both the support
      of the spontaneous processes and the initiation of new ones. Combining cognition,
      brain imaging and cognitive rehabilitation in MS, an intriguing question is
      whether fMRI can provide further insights into the mechanisms of induced
      plasticity and serve as objective outcome measures for efficient cognitive
      intervention.

PMID- 17503131
TI  - Qualitative and quantitative assessment of fatigue in multiple sclerosis (MS).
AB  - It was the aim of the present study to develop a synoptic multidimensional test
      system for assessment of fatigue in multiple sclerosis (MS) patients objectifying
      physical and mental fatigue as well as the subjective and objective standpoint in
      these two fatigue forms. Seventy nine patients with relapsing remitting multiple
      sclerosis (RRMS) and 51 age-matched healthy controls (H) were analysed by means
      of the physical fatigue test (hand dynamometer) and an objective mental fatigue
      test (vigilance test from the computerised Test Battery for Attentional
      Performance). Furthermore, subjective tiredness caused by test procedures,
      subjective persisting tiredness (Modified Fatigue Impact Scale; MFIS: physical
      and cognitive scale) and mood (Beck Depression Inventory; BDI-18) were
      analysed.MS patients differed significantly from the controls in their objective
      physical and mental performance under fatigue, as well as in their subjective
      estimation of tiredness. MS patients showed an inverse relationship between below
      average objective performance and high subjective feeling of tiredness when
      compared to controls. Subjectively severely tired MS patients achieved clearly
      poorer performances on the hand dynamometer test and slightly poorer performances
      on the vigilance test when compared to subjectively rarely tired MS patients.
      Depressed MS patients estimated their subjective tiredness in the MFIS
      significantly higher than non-depressed MS patients, but attained the same
      objective performance. This set of standardised tests enables meaningful
      comparisons between objective fatigue performance and subjective fatigue
      estimations in the physical and mental sphere and considers the influence of
      depression. Depression affects the subjective tiredness but not the objective
      fatigue performance.

PMID- 17503132
TI  - Stress and multiple sclerosis.
AB  - Increasing numbers of studies are reporting an association between stressful life
      events and exacerbation in multiple sclerosis. We review findings that begin to
      suggest psychological, social and biological factors that may be involved in this
      relationship. Depression, negative attributions, poor coping, and low social
      support have been implicated as aggravating the relationship between stress and
      exacerbation. A model of glucocorticoid resistance on immune cells is also
      presented as one potential biological mechanism. It is emphasized that to date
      there is no evidence of causal relationships. It is argued that a purely causal
      relationship, in which stressful events alone trigger exacerbation, is unlikely.
      Rather, we propose that stress may be one factor among many that influence risk
      of exacerbation.

PMID- 17503133
TI  - Influences on cognition by immunosuppression and immunomodulation in multiple
      sclerosis.
AB  - Cognitive impairment is common also in early stages of MS, but only little is
      known about its relationship to standard immunotherapeutic drugs. Present data
      suggest that both immunosuppressive as well as immunomodulatory therapy prevent
      or delay the onset and severity of cognitive impairment although reversible
      cognitive deficits can occur.

PMID- 17503134
TI  - Neuropsychiatric syndromes associated with multiple sclerosis.
AB  - Multiple sclerosis is associated with diverse behavioral changes. Rates of major
      depression approach 50% over the course of patients' lives, rates of bipolar
      disorder and psychosis are twice as common when compared to rates in the general
      population and pseudobulbar affect will afflict one in ten patients. However,
      these disorders often respond well to pharmacologic treatment and in the case of
      major depression, some forms of psychotherapy too. This article summarizes these
      mental state changes, their pathogenesis and treatment. Correct diagnosis and
      treatment can substantially improve the quality of life for MS patients.

PMID- 17503135
TI  - Cognitive dysfunction in different stages in multiple sclerosis--presentation of
      3 cases.
AB  - Although multiple sclerosis (MS) is a physically disabling disease, many patients
      also suffer from cognitive dysfunction in all stages of the disease. Recent
      studies have demonstrated that 45 up to 65% of MS patients are cognitively
      impaired. The profile of MS-related cognitive dysfunction varies greatly. It
      includes memory and learning deficits, attention deficits, executive dysfunction
      and visuo-spatial deficits. Most studies of cognition in MS examined patients in
      later stages, often including MS patients with marked physical disabilities. Our
      own studies revealed cognitive dysfunction in MS patients within the early stage
      of disease as well. In this paper, three patients with MS in different stages and
      with different MRI-findings will be presented in consideration of cognitive
      dysfunction in particular.

PMID- 17503136
TI  - Psychoneuroimmunology--cross-talk between the immune and nervous systems.
AB  - Psychoneuroimmunology is a relatively new field of study that investigates
      interactions between behaviour and the immune system, mediated by the endocrine
      and nervous systems. The immune and central nervous system (CNS) maintain
      extensive communication. On the one hand, the brain modulates the immune system
      by hardwiring sympathetic and parasympathetic nerves (autonomic nervous system)
      to lymphoid organs. On the other hand, neuroendocrine hormones such as
      corticotrophin-releasing hormone or substance P regulate cytokine balance. Vice
      versa, the immune system modulates brain activity including sleep and body
      temperature. Based on a close functional and anatomical link, the immune and
      nervous systems act in a highly reciprocal manner. From fever to stress, the
      influence of one system on the other has evolved in an intricate manner to help
      sense danger and to mount an appropriate adaptive response. Over recent decades,
      reasonable evidence has emerged that these brain-to-immune interactions are
      highly modulated by psychological factors which influence immunity and immune
      system-mediated disease.

PMID- 17503137
TI  - Long-term neuropsychological deficits after central nervous system infections
      despite adequate therapy.
AB  - Neuropsychological deficits are common consequences of central nervous system
      infections despite adequate treatment. The frequency and severity depends on the
      causative pathogen and the site(s) of injured brain parenchyma. The severity
      ranges from mild cognitive abnormalities not interfering with everyday life
      performance to fully developed Wernicke-Korsakow syndrome with complete inability
      to incorporate new information into long-term memory and to persistent vegetative
      state. In several conditions, rapid initiation of adequate therapy is crucial to
      minimise neuropsychological impairment.

PMID- 17503138
TI  - Neuropsychological symptoms in paraneoplastic disorders.
AB  - Neuropsychological symptoms may rarely be part of a paraneoplastic neurological
      syndrome, mainly as limbic encephalitis. As the tumour will not be known in most
      patients upon presentation to the neurologists, state-of-the art diagnosis
      including the use of anti-neuronal antibodies and FDG-PET is essential for
      adequate management of these patients.

PMID- 17503139
TI  - Neuropsychiatric disease in collagen vascular diseases and vasculitis.
AB  - The prevalence of neuropsychiatric symptoms in systemic lupus erythematosus
      varies between 37 and 95%; cognitive dysfunction, mood disorder, and anxiety
      syndromes are especially frequent. In Sjoegren's syndrome, cognitive dysfunction
      is combined with frontal executive disorder and attention deficit. Memory
      impairment, frontal executive dysfunction and personality changes have been
      reported in Behcet's disease. Classic polyarteritis nodosa, the Churg Strauss
      syndrome and Wegener's granulomatosis may be associated with cognitive changes
      due to inflammatory encephalopathy. Cranial arteritis belongs to the treatable
      causes of dementia. In primary angiitis of the CNS, small-vessel disease presents
      more frequently with encephalopathy.

PMID- 17503140
TI  - Psychosocial aspects in patients with myasthenia gravis.
AB  - Myasthenia gravis patients usually present with fluctuating, asymmetrical stress
      dependent weakness in the absence of other neurological disturbances. In weak
      patients psychopathological disturbances are frequently reported and misdiagnosed
      as a psychiatric disorder. The question to what extent psychiatric symptoms are
      involved in MG is still open. The case report presented here shows exemplary that
      psychopathological disturbances in exacerbated myasthenic patients are temporary
      and completely reversible after adequate somatic therapy.

PMID- 17503141
TI  - Neuropsychological/-psychiatric deficits in immune-mediated neuropathies.
AB  - Albeit common, neuropsychological/psychiatric deficits in patients with
      autoimmune-mediated neuropathies have not received much attention; however, they
      can impose a considerable clinical problem. Especially in intensive-care treated
      Guillain Barre syndrome (GBS) severe psychosis may occur which may go
      unrecognised due to the severity of the neurological motor deficits. Fatigue may
      result in a major restriction of quality of life long after the acute phase of
      GBS and is also a major debilitating factor in chronic inflammatory neuropathies.
      Symptomatic treatment remains largely empirical.

PMID- 17503142
TI  - Autonomic dysfunction in Guillain-Barre syndrome and multiple sclerosis.
AB  - This review gives an overview of autonomic dysfunction encountered in Guillain
      Barre syndrome (GBS) and multiple sclerosis (MS). In GBS, cardiovascular
      dysregulation is common and may lead to serious bradyarrhythmias that need to be
      recognised for the early initiation of appropriate therapy. Although standardised
      autonomic tests were useful for the diagnosis of autonomic failure, they were not
      able to indicate vagal over-reactivity. In this regard, eyeball pressure testing
      may correctly identify patients at risk for impending and potentially life
      threatening bradyarrhythmias which may easily be administered at the bedside. In
      MS, cardiovascular autonomic dysfunction is usually of minor clinical importance.
      However, orthostatic intolerance may be present in approximately 50% of patients
      and could easily be detected by routine measurements of heart rate and blood
      pressure during rest and during standing. More subtle alterations may require
      more sophisticated methods such as autonomic reflex testing or baroreflex
      stimulation. Several in vitro, animal and clinical studies provide evidence that
      there are many interactions between the sympathetic nervous system and the immune
      system giving rise to the hypothesis that autonomic dysfunction in MS may not
      only be a consequence of the disease, but may in itself affect the course of MS.

PMID- 17503145
TI  - Abstracts of the 17th meeting of the European Neurological Society, 16-20 June
      2007, Rhodes, Greece.

PMID- 17503146
TI  - Sustainability evaluation of the Grain for Green Project: from local people's
      responses to ecological effectiveness in Wolong Nature Reserve.
AB  - This article examines the sustainability of the Grain for Green Project in the
      Wolong Nature Reserve. Pertinent data were collected through a questionnaire
      survey and a spatial analysis of reforested lands. The study results identified
      four critical issues that may influence the sustainability of the project in the
      study area. The first issue is concerned with the project's impacts on local
      sustenance. Because local grain consumption depends greatly on compensation
      awarded by the project, the potential for sustainability of the project is
      compromised. The second issue is that the project causes negative effects on
      local incomes in the Wolong Nature Reserve, which may undermine local economic
      prospects. The third issue is that the project failed to deliver suitable habitat
      for the giant panda, although two of the suitability requirements that deal with
      landform features were met. Lastly, the project neglects great differences among
      geographical areas in the country, providing the same compensation and length of
      compensation period to all participants. Appropriate compensation mechanisms
      should be established and adapted to local economic, environmental, and social
      conditions. In managing nature reserves and moving toward sustainability,
      ensuring all aspects of local socioeconomic and ecological/environmental issues
      are properly addressed is a real challenge. Based on our study, some
      recommendations for improving sustainability of the project are given.

PMID- 17503147
TI  - Isolation and characterization of two genes that encode active glucoamylase
      without a starch binding domain from Rhizopus oryzae.
AB  - Glucoamylase obtained from Rhizopus sp. is frequently preferred for certain
      applications of starch modification or saccharification. The predominant enzyme,
      which contains a starch-binding domain on the amino terminus, has been previously
      characterized from several species. Additionally, the cDNA encoding this protein
      was cloned and found to show 100% identity to a R. oryzae strain 99-880 that has
      recently been sequenced by the Broad Institute of Harvard and Massachusetts
      Institute of Technology. Analysis of this genome indicates coding regions for two
      additional glucoamylase genes, amyC and amyD, lacking a starch-binding domain.
      The two genes encode proteins that are approximately 50% identical to the
      catalytic region of the AmyA protein and 67% identical to each other. The
      predicted AmyC and AmyD proteins contain the highly conserved signature sequences
      of Family 15 glycoside hydrolases. The two genes appear to be transcriptionally
      expressed in cultures grown in fermentable and gluconeogenic carbon sources. The
      predicted 49.7-kD AmyC and 48.8-kD AmyD proteins were expressed in several
      different ways using Pichia pastoris. When the sequence for putative secretion
      signal was left intact, glucoamylase activity was detected in the crude cell
      extracts, but no activity was present in the growth medium. However, replacement
      of this region with the yeast alpha-secretion signal resulted in secretion of
      active glucoamylase that was able to degrade soluble starch.

PMID- 17503148
TI  - Across genus plasmid transformation between Bacillus subtilis and Escherichia
      coli and the effect of Escherichia coli on the transforming ability of free
      plasmid DNA.
AB  - The results presented in this article show that direct plasmid transfer from
      Escherichia coli carrying shuttle plasmid to Bacillus subtilis occurred when
      close contact between the two species was established by mixing E. coli and B.
      subtilis onto selective agar plates. The data demonstrate that the production of
      resistant colonies by plasmid transformation through cell contact was DNase I
      sensitive and dependent on transformable B. subtilis strains. Furthermore,
      another observation indicated that the E. coli strain is able to affect the
      transformation capability of B. subtilis. It is assumed that the donor strain is
      a momentous factor for taking up plasmid DNA. This conclusion is significant in
      the assessment of both the possibility of intercellular DNA transfer in natural
      habitats of micro-organisms and the risk of the application of genetically
      engineered micro-organisms.

PMID- 17503149
TI  - Improvement of a chemically defined medium for the sustained growth of
      Lactobacillus plantarum: nutritional requirements.
AB  - The aims of this work were to improve a basal synthetic medium (BM) for the
      growth of Lactobacillus plantarum strains and to establish their amino-acid
      requirements. Amino-acid use was analyzed in the most nutritionally demanding
      bacterium. First, the improved BM (L. plantarum synthetic medium [LPSM]) was
      created by increasing some vitamins in the BM, especially p-aminobenzoic acid,
      vitamin B(12), and biotin; 5-fold phenylalanine, histidine, isoleucine, leucine,
      lysine, methionine, proline, serine, threonine, and tryptophan; and 10-, 60-, and
      75-fold valine, arginine, and tyrosine, respectively. With these additions, the
      N8 and N4 strains of L. plantarum grew rapidly to reach final cell densities
      similar to those obtained in Mann-Rogosa-Sharpe medium. When cysteine, leucine,
      valine, isoleucine, threonine, and glutamic acid were individually removed from
      this medium, bacterial growth significantly decreased or ceased, indicating that
      these amino acids are essential for growth. The N4 strain also required lysine
      and tryptophan in addition to the six amino acids necessary for growth. L.
      plantarum N4 mainly consumed essential amino acids, such as valine, lysine,
      cysteine, and threonine as well as the stimulatory amino acid, arginine. Thus,
      the BM was improved mainly on the basis of annulling limitations with respect to
      amino acids. With this, improved medium cell densities in the order of 10(9)
      colony-forming units/mL have been achieved, indicating that LPSM medium could be
      used for conducting metabolic and genetic studies on L. plantarum. Their low
      levels in orange juice suggest that these amino acids may not satisfy the total
      nitrogen requirement for the development of L. plantarum in the natural
      environment.

PMID- 17503150
TI  - Light-dependent assimilation of trans-cinnamate by Rhodobacter sphaeroides OU5.
AB  - We present a novel light-dependent metabolism of an aromatic compound (trans
      cinnamate) that is assimilatory rather than dissimilatory. Light-dependent
      assimilation of trans-cinnamate was observed by both growing and resting cells of
      Rhodobacter sphaeroides OU5. Trans-cinnamate assimilation could be correlated
      with simultaneous formation of both phenylalanine and tyrosine at near
      stoichiometric ratios. Trans-cinnamate assimilation was promoted by carbon source
      and electron donors, such as glucose, pyruvate, or alpha-ketoglutarate, whereas
      malate, succinate, fumarate, and acetate were inhibitory.

PMID- 17503151
TI  - Role of transglycosylation products in the expression of multiple xylanases in
      Myceliophthora sp. IMI 387099.
AB  - This study reports the regulation of multiple xylanases produced by
      Myceliophthora sp. IMI 387099. Fructose was found to positively regulate the
      expression of multiple xylanase when used as sole carbon source. The xylanases
      (EX(1 )and EX(2)) of acidic pI were expressed in the presence of simple sugars
      (glucose, arabinose, and xylose), whereas xylanase of both acidic as well as
      basic pI (EX(1,) EX(2,) EX(3), and EX(5)) were expressed in the presence of
      fructose, xylan, and combination of xylan and alcohol. The combination of
      fructose and xylan also led to expression of an additional xylanase (EX(4)). The
      positional isomer (iso-X4) was found to be the key transglycosylation product
      when cultures were grown in the presence of fructose and xylan. In the presence
      of alcohols, the higher expression of xylanase was ascribed to the synergistic
      effect of alkyl glycoside and other transglycosylation products present in the
      culture extracts.

PMID- 17503152
TI  - Raising our heads above the parapet: ES not NOTES.

PMID- 17503154
TI  - Site-directed gene integration in transgenic zebrafish mediated by cre
      recombinase using a combination of mutant lox sites.
AB  - With current gene-transfer techniques in fish, insertion of DNA into the genome
      occurs randomly and in many instances at multiple sites. Associated position
      effects, copy number differences, and multiple gene interactions make gene
      expression experiments difficult to interpret and fish phenotype less
      predictable. To meet different fish engineering needs, we describe here a gene
      targeting model in zebrafish. At first, four target zebrafish lines, each
      harboring a single genomic lox71 target site, were generated by zebrafish
      transgenesis. The zygotes of transgenic zebrafish lines were coinjected with
      capped Cre mRNA and a knockin vector pZklox66RFP. Site-specific integration event
      happened from one target zebrafish line. In this line two integrant zebrafish
      were obtained from more than 80,000 targeted embryos (integrating efficiency
      about 10(-4) to 10(-5)) and confirmed to have a sole copy of the integrating DNA
      at the target genome site. Genomic polymerase chain reaction analysis and DNA
      sequencing verified the correct gene target events where lox71 and lox66 have
      accurately recombined into double mutant lox72 and wild-type loxP. Each integrant
      zebrafish chosen for analysis harbored the transgene rfp at the designated egfp
      concatenates. Although the Cre-mediated recombination is site specific, it is
      dependent on a randomly placed target site. That is, a genomic target cannot be
      preselected for integration based solely on its sequence. Conclusively, an rfp
      reporter gene was successfully inserted into the egfp target locus of zebrafish
      genome by Cre-lox-mediated recombination. This site-directed knockin system using
      the lox71/lox66 combination should be a promising gene-targeting platform serving
      various purposes in fish genetic engineering.

PMID- 17503155
TI  - Analysis of prognostic factors affecting survival after initial recurrence and
      treatment efficacy for recurrence in patients undergoing potentially curative
      hepatectomy for hepatocellular carcinoma.
AB  - BACKGROUND: Survival analysis in patients with initial recurrence after curative
      hepatectomy for hepatocellular carcinoma (HCC) has not been well evaluated. In
      addition, selections of the most effective treatments for patients with recurrent
      HCC still remain controversial. METHODS: Three hundred and nineteen patients who
      underwent potentially curative hepatectomies were followed for initial
      recurrence, and factors predictive of recurrence were determined. The factors
      affecting survival including pattern of recurrence and treatment modalities from
      the time of initial recurrence in 211 patients were retrospectively analyzed.
      RESULTS: The overall 5-year disease-free survival rate of 319 patients was 31.1%.
      The 5-year survival rate of 211 patients from the time of initial recurrence was
      31.9%. In a multivariate analysis, a low indocyanine green retention rate, lack
      of liver cirrhosis, a long interval before recurrence, the absence of portal vein
      invasion, and intrahepatic recurrence (<or=3 nodules) were shown to be
      significantly favorable prognostic factors after the initial recurrence. The 5
      year survival rate of patients with intrahepatic recurrence (<or=3 nodules) was
      42.3%, and no survival differences were observed among different treatment
      modalities. CONCLUSION: When the initial recurrence occurred after a longer
      interval, and/or with three or fewer intrahepatic recurrent nodules, a favorable
      prognosis could be expected in those patients with better liver function and no
      portal vein invasion at the time of the primary hepatectomy. It is important to
      conduct a randomized controlled trial to clarify a method for selecting optimal
      treatment in patients with a smaller number of initial intrahepatic recurrences.

PMID- 17503156
TI  - Failure analysis of recurrent disease following complete cytoreduction and
      perioperative intraperitoneal chemotherapy in patients with peritoneal
      carcinomatosis from colorectal cancer.
AB  - BACKGROUND: The aim of this study was to analyze the anatomic distribution,
      timing, and outcomes of recurrent disease after complete cytoreduction and
      perioperative intraperitoneal chemotherapy (PIC) for peritoneal carcinomatosis of
      colorectal origin. METHODS: Data regarding all patients who underwent complete
      cytoreduction and PIC for carcinomatosis from colorectal cancer were extracted
      from a prospectively collected database. The information regarding recurrent
      disease found on diagnostic evaluation and/or abdominal exploration was analyzed.
      RESULTS: Seventy patients underwent complete cytoreduction and perioperative
      intraperitoneal chemotherapy, and 49 of them had documented recurrent disease.
      The median time to progression for these 49 patients was 9 months while their
      median survival was 30 months. Eighteen patients had a localized intra-abdominal
      recurrence, 10 had diffuse intraperitoneal recurrence, 10 had isolated distant
      metastases, and 11 had a combination of distant metastases and intra-abdominal
      recurrence. There was a statistically significant difference in survival for
      patients with different patterns of recurrence (P = .012). Twenty-six patients
      underwent a second operation. The median survival of these patients was
      significantly longer than that of patients who did not have a second operation
      (39 vs 20 months, P = .0003). Four of the 49 patients with recurrences were still
      alive at the time of last follow-up, and three of them have no evidence of
      disease 73, 96, and 206 months after the diagnosis of recurrence. CONCLUSIONS:
      Recurrence is a frequent event after optimal cytoreduction and PIC for
      carcinomatosis from colorectal cancer. Surgical treatment for a selected group of
      patients with recurrent disease may result in long-term survival.

PMID- 17503157
TI  - Use of an artificial lymphatic system during carboplatin infusion to improve
      canine osteosarcoma blood flow and clinical response.
AB  - BACKGROUND: The artificial lymphatic system (ALS), a mechanical system designed
      to reduce increased interstitial fluid pressure in solid tumors and enhance the
      delivery of chemotherapy, was evaluated within a randomized clinical trial
      treating spontaneously occurring canine appendicular osteosarcoma (OS), a tumor
      similar to its human OS counterpart. METHODS: An ALS was investigated for its
      ability to increase OS blood flow and increase uptake of intravenously
      administered carboplatin. RESULTS: Blood flow increased by 314% in tumors with
      active ALS drains versus 126% in control tumors (P < .03). Tumor carboplatin
      uptake increased by 51% after drain activation (P = .07). Microvascular density
      (MVD) was measured in tumors after surgical amputation and in corresponding bone
      regions in a cohort of normal dogs. The OS tumors had equivalent MVD as normal
      bone, and MVD was higher in the humerus than the femur (P < .03) in both tumor
      and normal bone. Median survival between the ALS-treated and control cohorts was
      not different despite increased drug uptake or ALS manipulation. Compared with
      historic controls, ALS drain insertion into tumors to reduce interstitial fluid
      pressure did not worsen the prognosis. CONCLUSIONS: The findings in canine
      spontaneously occurring OS indicate that an ALS may be of value as a chemotherapy
      adjunct for enhancing the delivery of chemotherapy to tumor interstitium.

PMID- 17503160
TI  - Secondary perineal hernia following open abdominoperineal excision of the rectum:
      report of a case and review of the literature.
AB  - This is a case report of a 46-year-old man who presented with a painful perineal
      lump four months after abdominoperineal excision of the rectum (APER) with pre
      operative radiotherapy and adjuvant chemotherapy. Perineal hernia (suspected
      clinically) was confirmed by magnetic resonance imaging, and the patient
      underwent open Permacol mesh repair via a perineal approach. Symptomatic perineal
      herniation after surgical resection is a rare phenomenon, and the approach to
      management remains challenging. Several different surgical approaches and
      techniques of repair have been described. In this report, we review the
      literature surrounding the presentation, aetiology and repair of this unusual
      post-operative complication. Furthermore, our case confirms that closure of the
      hernial orifice with mesh via a perineal approach is a satisfactory technique.

PMID- 17503161
TI  - Strategies of smoking cessation intervention before hernia surgery--effect on
      perioperative smoking behavior.
AB  - BACKGROUND: Although it is now generally accepted that patients should be advised
      to quit smoking before surgery, the effect of low-intensive smoking cessation
      intervention, both on preoperative smoking behavior and on risk reduction,
      remains unclear. Our objective was to study the effect on perioperative smoking
      behavior and on postoperative wound infection of different types of low-intensive
      intervention before herniotomy. METHODS: Between October 1998 and October 2000,
      180 consecutive smokers scheduled for elective herniotomy were advised to quit
      smoking perioperatively and subsequently allocated randomly to three low
      intensive smoking cessation groups: a standard (control) group, a telephone
      group, which was reminded by telephone, and an out-patient group, which was
      reminded by means of an out-patient talk and demonstration of nicotine
      replacement drugs. Spontaneous perioperative smoking behavior was recorded for 64
      consecutive non-advised smokers. Postoperative wound infection was evaluated by
      independent assessors. RESULTS: Of the advised patients, 19% (29/149) stopped
      smoking before surgery compared with 2% (1/64) in the non-advised cohort (P <
      0.01). In the standard group 13% (6/48) quit smoking compared with 23% (23/101)
      in the pooled telephone and outpatient group (NS). In the last group 64% (65/101)
      reduced or stopped smoking compared with 42% (20/48) in the standard group (P <
      0.05). Predictors of failed perioperative cessation of smoking were a CO breath
      test at inclusion above 20 ppm (OR: 0.11; 0.02-0-57) and low motivation to quit
      smoking (OR: 0.25; 0.09-0.70). Wound infection occurred in 6% (13/213) and there
      was no difference between the groups. CONCLUSION: Low-intensive smoking cessation
      intervention helps approximately one fifth of patients to stop smoking
      perioperatively. Patients who are reminded in addition to preoperative advice are
      more likely to stop or reduce smoking. Failure to stop smoking is greater if the
      patients are not motivated and if the CO breath test is high at the time of the
      preoperative advice.

PMID- 17503162
TI  - Comparative study and mutational analysis of distinctive structural elements of
      hyperthermophilic enzymes.
AB  - Comparison of the three-dimensional structure of hyperthermophilic and mesophilic
      beta-glycosidases shows differences in secondary structure composition. The
      enzymes from hyperthermophilic archaea have a significantly larger number of beta
      strands arranged in supernumerary beta-sheets compared to mesophilic enzymes from
      bacteria and other organisms. Amino acid replacements designed to alter the
      structure of the supernumerary beta-strands were introduced by site directed
      mutagenesis into the sequence encoding the beta-glycosidase from Sulfolobus
      solfataricus. Most of the replacements caused almost complete loss of activity
      but some yielded enzyme variants whose activities were affected specifically at
      higher temperatures. Far-UV CD spectra recorded as a function of temperature for
      both wild type beta-glycosidase and mutant V349G, one of the mutants with reduced
      activity at higher temperatures, were similar, showing that the protein structure
      of the mutant was stable at the highest temperatures assayed. The properties of
      mutant V349G show a difference between thermostability (stability of the protein
      structure at high temperatures) and thermophilicity (optimal activity at high
      temperatures).

PMID- 17503163
TI  - Correlation between thermal aggregation and stability of lysozyme with salts
      described by molar surface tension increment: an exceptional propensity of
      ammonium salts as aggregation suppressor.
AB  - Protein aggregation is a critical problem for biotechnology and pharmaceutical
      industries. Despite the fact that soluble proteins have been used for many
      applications, our understanding of the effect of the solution chemistry on
      protein aggregation still remains to be elucidated. This paper investigates the
      process of thermal aggregation of lysozyme in the presence of various types of
      salts. The simple law was found; the aggregation rate of lysozyme increased with
      increasing melting temperature of the protein (T (m)) governed by chemical
      characteristics of additional salts. Ammonium salts were, however, ruled out; the
      aggregation rates of lysozyme in the presence of the ammonium salts were smaller
      than the ones estimated from T (m). Comparing with sodium salts, ammonium salts
      increased the solubility of the hydrophobic amino acids, indicating that ammonium
      salts adsorb the hydrophobic region of proteins, which leads to the decrease in
      aggregation more effectively than sodium salts. The positive relation between
      aggregation rate and T (m) was described by another factor such as the surface
      tension of salt solutions. Fourier transform infrared spectral analysis showed
      that the thermal aggregates were likely to form beta-sheet in solutions that give
      high molar surface tension increment. These results suggest that protein
      aggregation is attributed to the surface free energy of the solution.

PMID- 17503164
TI  - The correlation of cold denaturation temperature with surface stability factor of
      proteins.
AB  - Cold denaturation is an intriguing phenomenon in protein denaturation for
      elucidating protein accessible surface area (ASA). Compared to the impact of
      protein surface, the importance of protein-water interactions in cold
      denaturation may be ruled out significantly. Here, based on the ASA, we have
      defined a new factor, the surface stability factor (SSF). From the SSF, in
      combination with the cold denaturation temperature (T(g')) or temperature at
      DeltaS = 0 (T(s)) of a given protein, one can predict the percent of hydrophobic
      surface area (H), percent of total surface there on positive and negative charge
      sum (effective charge) be zero (C), percent of patches hydrophobicity (HP) and
      others critical surface parameters without any need to the crystallographic data.

PMID- 17503165
TI  - Purification, characterization and cloning of a chymotrypsin inhibitor (CI-9)
      from the hemolymph of the silkworm, Bombyx mori.
AB  - Hemolymph chymotrypsin inhibitor 9 (CI-9) from the hemolymph of the silkworm,
      Bombyx mori, was purified by ammonium sulfate precipitation, Butyl Toyopearl
      hydrophobic chromatography, gel filtration through Sephadex C-50 and chymotrypsin
      sepharose 4B affinity chromatography. Checked by Native PAGE and SDS-PAGE in
      combination with silver staining, the final preparation appeared homogeneous. In
      tricine SDS-PAGE, CI-9 displayed a molecular weight of 7.5 kD, which was
      determined to be 7167 Da with the Voyager TOFMass analyser. The pI value for CI
      9, revealed by 2D-PAGE (two-dimensional polyacrylamide gel electrophoresis), was
      4.3. CI-9 exhibited inhibitory activity at a temperature as high as 100 degrees C
      and a stability against a wide range of pH (1-12). In N-terminal amino-acid
      analysis of CI-9, 40 amino acid residues were obtained. The C-terminal 22 amino
      acid residues were deduced by subsequently cloned cDNA and genomic fragments. MW
      and pI of CI-9 were predicted to be 7170.98 Da and 4.61, respectively, on the
      website. Its low molecular weight, high stability, conserved active site and
      Kunitz domain showed that CI-9 is a Kunitz-type CI. The difference of sequence
      and pI between CI-9 and other Kunitz type CIs indicated that it is a novel
      chymotrypsin inhibitor.

PMID- 17503166
TI  - Amaranth globulin polypeptide heterogeneity.
AB  - The polypeptides integrating amaranth globulin-p and 11S-globulin were
      characterized by two-dimensional electrophoresis, ion-exchange chromatography and
      RP-HPLC. All polypeptides exhibited charge and hydrophobic heterogeneity. Almost
      all acid (A, pI 5-7) and basic (B, pI 9-10) polypeptides were present in both
      globulins, and the same happened with the unprocessed M polypeptides with pI in
      the range of 7-7.5 which fits well with a sequence containing both the A and B
      polypeptides. There were other polypeptides only present in 11S-globulin, like
      some of 41 and 16 kDa, which might come from another precursor or be the products
      of a different processing of the propolypeptide. These results suggested that,
      although amaranth subunits from different subfamilies are interchangeable in
      different oligomers, some structural differences between them might affect the
      assembly of globulin molecules. Structural differences arising from this behavior
      could account for the different physicochemical properties of globulin molecules.

PMID- 17503167
TI  - Unfolding and refolding of bovine alpha-crystallin in urea and its chaperone
      activity.
AB  - We undertook an unfolding and refolding study of alpha(L)-crystallin in presence
      of urea to explore the breakdown and formation of various levels of structure and
      to find out whether the breakdown of various levels of structure occurs
      simultaneously or in a hierarchal manner. We used various techniques such as
      circular dichroism, fluorescence spectroscopy, light scattering, polarization to
      determine the changes in secondary, tertiary, and quaternary structure. Unfolding
      and refolding occurred through a number of intermediates. The results showed that
      all levels of structure in alpha(L)-crystallin collapsed or reformed
      simultaneously. The intermediates that occurred in the 2-4 M urea concentration
      range during unfolding and refolding differed from each other in terms of the
      polarity of the tryptophan environment. The ANS binding experiments revealed that
      refolded alpha(L)-crystallin had higher number of hydrophobic pockets compared to
      native one. On the other hand, polarity of these pockets remained same as that of
      the native protein. Both light scattering and polarization measurements showed
      smaller oligomeric size of refolded alpha(L)-crystallin. Thus, although the
      secondary structural changes were almost reversible, the tertiary and quaternary
      structural changes were not. The refolded alpha(L)-crystallin had more exposed
      hydrophobic sites with increased binding affinity. The refolded form also showed
      higher chaperone activity than native one. Since the refolded form was smaller in
      oligomeric size, some buried hydrophobic sites were available. The higher
      chaperone activity of lower sized oligomer of alpha(L)-crystallin again revealed
      that chaperone activity was dependent on hydrophobicity and not on oligomeric
      size.

PMID- 17503169
TI  - Analysis of reflex modulation with a biologically realistic neural network.
AB  - In this study, a neuromusculoskeletal model was built to give insight into the
      mechanisms behind the modulation of reflexive feedback strength as experimentally
      identified in the human shoulder joint. The model is an integration of a
      biologically realistic neural network consisting of motoneurons and interneurons,
      modeling 12 populations of spinal neurons, and a one degree-of-freedom
      musculoskeletal model, including proprioceptors. The model could mimic the
      findings of human postural experiments, using presynaptic inhibition of the Ia
      afferents to modulate the feedback gains. In a pathological case, disabling one
      specific neural connection between the inhibitory interneurons and the
      motoneurons could mimic the experimental findings in complex regional pain
      syndrome patients. It is concluded that the model is a valuable tool to gain
      insight into the spinal contributions to human motor control. Applications lay in
      the fields of human motor control and neurological disorders, where hypotheses on
      motor dysfunction can be tested, like spasticity, clonus, and tremor.

PMID- 17503170
TI  - The G619A Aa-nat gene polymorphism does not contribute to sleep time variation in
      the Brazilian population.
AB  - Genes involved in melatonin synthesis, such as Aa-nat, may be important for our
      understanding of diurnal preference and circadian rhythm disturbances in humans.
      In Japan, Hohjoh et al. reported increased allelic frequencies of the 619A allele
      of the G619A Aa-nat gene polymorphism in a sample of Delayed Sleep Phase Syndrome
      (DSPS) patients. The present study sought to analyze G619A polymorphism frequency
      in a Brazilian sample, including DSPS patients. We found almost no allelic
      variation for G619A polymorphism in our sample, except for two heterozygous
      samples out of 551. Our results leave open the question of whether there would be
      an association if there were some genetic variation in our population. It is
      important to analyze different ethnic groups in order to validate the effect of
      G619A polymorphism on sleep timing.

PMID- 17503171
TI  - Community-based voluntary counseling and testing services in rural communities of
      Chiang Mai Province, Northern Thailand.
AB  - Between September, 2002 to May, 2003, we implemented community-based HIV
      Voluntary Counseling and Testing (VCT) services in four rural areas of Chiang Mai
      Province. The services included providing HIV/AIDS education and free mobile VCT
      using rapid testing with same day results. Overall, 427 villagers came for VCT
      (testers) and consented to be interviewed. HIV prevalence among testers was 4.9%,
      range from 1.1 to 8.4% by area. 'It is free' and/or 'convenient' were the most
      frequently cited factors that motivated them to get tested (72%) from our mobile
      VCT. Rural residents came for VCT when logistical barriers were removed. HIV
      prevalence among testers in some areas was high. Without extending HIV prevention
      efforts to population segments with less access to health care, the HIV problem
      in Thailand may re-emerge. Convenient and low-cost VCT may prove crucial for
      containing this HIV epidemic.

PMID- 17503172
TI  - Medication adherence mediates the relationship between adherence self-efficacy
      and biological assessments of HIV health among those with alcohol use disorders.
AB  - The current study examines the relationship between negative consequences of
      alcohol use, adherence self-efficacy, medication adherence, and biological
      markers of HIV health (CD4 count and viral load). A total of 275 HIV-positive men
      and women with alcohol use disorders were surveyed using Audio-CASI measures and
      time line followback interviews. Findings from a structural equation model
      suggest that negative consequences related to alcohol use did not directly impact
      HIV health. Adherence self-efficacy had direct effects on viral load, but not CD4
      count. Mediation analyses indicated that self-reported adherence partially
      mediated the relationship between adherence self-efficacy and viral load.
      Cognitive-oriented interventions aimed at facilitating adherence self-efficacy
      may be effective in improving both medication adherence and HIV health. If
      facilitating confidence improves HIV health, then health care providers can make
      a strong impact by spending a few short minutes themselves and/or partnering with
      behavioral health clinicians using techniques like motivational enhancement.

PMID- 17503174
TI  - Fundamental movement skills and children with attention-deficit hyperactivity
      disorder: peer comparisons and stimulant effects.
AB  - The purpose of this study was to compare the fundamental movement skills of 22
      children with attention-deficit hyperactivity disorder (ADHD), from 6 to 12 years
      of age, to gender- and age-matched peers without ADHD and assess the effects of
      stimulant medication on the movement skill performance of the children with ADHD.
      Repeated measures analyses revealed significant skill differences between
      children with and without ADHD (p <or= 0.001). Results from the stimulant
      medication trials indicated no significant effect of medication on the movement
      skill patterns of children with ADHD. It is concluded that children with ADHD may
      be at risk for developmental delays in movement skill performance. Potential
      factors underlying the movement skill difficulties are discussed, with
      suggestions for future research.

PMID- 17503173
TI  - Are motor inhibition and cognitive flexibility dead ends in ADHD?
AB  - Executive dysfunction has been postulated as the core deficit in ADHD, although
      many deficits in lower order cognitive processes have also been identified. By
      obtaining an appropriate baseline of lower order cognitive functioning light may
      be shed on as to whether executive deficits result from problems in lower order
      and/or higher order cognitive processes. We examined motor inhibition and
      cognitive flexibility in relation to a baseline measure in 816 children from ADHD
      and control families. Multiple children in a family were tested in order to
      examine the familiality of the measures. No evidence was found for deficits in
      motor inhibition or cognitive flexibility in children with ADHD or their
      nonaffected siblings: Compared to their baseline speed and accuracy of
      responding, children with ADHD and their (non)affected siblings were not
      disproportionally slower or inaccurate when demands for motor inhibition or
      cognitive flexibility were added to the task. However, children with ADHD and
      their (non)affected siblings were overall less accurate than controls, which
      could not be attributed to differences in response speed. This suggests that
      inaccuracy of responding is characteristic of children having (a familial risk
      for) ADHD. Motor inhibition and cognitive flexibility as operationalized with
      mean reaction time were found to be familial. It is concluded that poorer
      performance on executive tasks in children with ADHD and their (non)affected
      siblings may result from deficiencies in lower order cognitive processes and not
      (only) from higher order cognitive processes/executive functions.

PMID- 17503175
TI  - Early-occurring maternal depression and maternal negativity in predicting young
      children's emotion regulation and socioemotional difficulties.
AB  - This longitudinal investigation examined the effects of maternal depression and
      concomitant negative parenting behaviors on children's emotion regulation
      patterns and socioemotional functioning. One hundred fifty-one mothers and their
      children were assessed when children were approximately 1 1/2-, 3-, 4-, and 5
      years of age. Ninety-three of the children had mothers with a history of Major
      Depressive Disorder (MDD) that had occurred within the first 21 months of the
      child's birth, and 58 of the children had mothers without any history of MDD.
      Early-occurring Initial maternal depression predicted children's dysregulated
      emotion patterns at age 4 and decreased perceived competence ratings at age 5.
      Initial maternal depression also indirectly predicted decreased child social
      acceptance ratings at age 5 through its association with dysregulated emotion
      patterns. Furthermore, the relation between maternal depression and children's
      decreased social acceptance was more pronounced in those offspring with a history
      of high versus low maternal negativity exposure. Findings increase understanding
      of the processes by which maternal depression confers risk on children's
      socioemotional adjustment.

PMID- 17503176
TI  - Marital conflict and risk for child maladjustment over time: skin conductance
      level reactivity as a vulnerability factor.
AB  - Skin conductance level reactivity (SCLR) was examined as a longitudinal mediator
      and moderator of relations between parental marital conflict and psychopathology
      among children and young adolescents. Participants were 157 boys and girls (M age
      at T1 = 9.31 years; SD = 1.97); there was a 2-year lag between T1 and T2
      assessments. At T1, participants' SCLR was assessed in response to lab
      challenges. Parents completed measures of aggressive marital conflict and child
      adjustment at T1 and T2. Supportive of moderation effects, T1 marital conflict
      interacted with T1 SCLR and gender in the prediction of changes in maladjustment.
      The link between marital conflict and increased internalizing and externalizing
      symptoms was stronger for girls with higher SCLR than girls with lower SCLR.
      Marital conflict predicted increased externalizing behaviors for boys with lower
      SCLR but not higher SCLR, although levels of externalizing behaviors were similar
      among boys with lower and higher SCLR especially at higher levels of marital
      conflict. Findings build on the literature by illustrating the importance of
      examinations of both family risk and youth biological vulnerability for the
      prediction of psychopathology.

PMID- 17503177
TI  - Do friends' characteristics moderate the prospective links between peer
      victimization and reactive and proactive aggression?
AB  - This study examined (a) the predictive link between peer victimization and
      children's reactive and proactive aggression, and (b) the potential moderating
      effect of reciprocal friends' reactive and proactive aggression in this context.
      The study also examined whether these potential moderating effects of friends'
      characteristics were stronger with respect to more recent friends compared to
      previous friends. Based on a convenience sample of 658 twin children (326 boys
      and 332 girls) assessed in kindergarten and first grade, the results showed that
      peer victimization uniquely predicted an increase in children's teacher-rated
      reactive aggression, but not teacher-rated proactive aggression. The relation of
      peer victimization to increased reactive aggression was, however, moderated by
      recent not previous reciprocal friends' similarly aggressive characteristics.
      These findings, however, tended to be mostly true for boys, but not for girls.
      The findings are discussed in terms of their theoretical and practical
      implications for victimized children's risk of displaying reactive and proactive
      aggressive behaviors.

PMID- 17503178
TI  - Screening of PAHs and DDTs in sand and acrisols soil by a rapid solid-phase
      microalgal bioassay.
AB  - Previously we have demonstrated the rapid screening potential of a newly
      developed solid-phase microalgal bioassay with spiked sands. In this paper, we
      report further comparative results using both PAHs and DDTs spiked sands and
      field-collected acrisols soils. Toxicity responses obtained from standard higher
      plant tests with three species of plants (Lolium perenne, Cynodon dactylon and
      Brassica chinensis) were compared with those obtained from a cocktail of
      microalgae (Selenastrum capricornutum, Chlorococcum hypnosporum and the
      indigenous Chlorococcum meneghini). The 5-day seed germination/root elongation
      tests were not sensitive at all in contrast to the 4-day solid-phase microalgal
      tests and the 28-day early seedling growth tests in both spiked sands and
      contaminated soils. Sensitivities of microalgal tests were generally higher than
      the seedling growth tests in spiked sands. Concerning the assays with
      contaminated soil, the responses of microalgae and higher plants varied. However,
      the results demonstrated that microalgae could generally act as effective
      surrogates to screen xenobiotic compounds at toxic level to higher plants, with
      the local species C. meneghini especially sensitive to reveal phytotoxic effects.
      This promising rapid screening solution is possible to be used in accompany with
      standard seedling growth tests when assessing phytotoxicities of contaminated
      areas, especially for acrisols soil.

PMID- 17503179
TI  - Behavioral response of zebrafish Danio rerio Hamilton 1822 to sublethal stress by
      sodium hypochlorite: ecotoxicological assay using an image analysis biomonitoring
      system.
AB  - We evaluated behavioral responses of zebrafish Danio rerio exposed to sublethal
      concentrations of sodium hypochlorite using an image analysis biomonitoring
      system (IABS). First, the limits of normal variation in swimming activity of
      zebrafish were determined by monitoring traveled distance of 40 control fishes
      using the IABS. An acute toxicity test was performed to determine the LC(50(24
      h)) for D. rerio to NaOCl. To evaluate the toxic effects in swimming activity, 32
      fishes were exposed to 40%, 30%, 20%, 10% of the LC(50 )and 32 were used as
      control using the IABS. We considered toxic concentrations where more than 10%
      intervals of the treated group were below the limits of normal variation and were
      significantly different from the control group. Two main responses were observed:
      an escape response (increased swimming activity) at 10% treated group, a gradual
      decrease in swimming activity from the 20% of the LC(50) on, and an avoidance
      response at higher concentrations. The response of the 20% treated group were
      considered as a NOAEL and responses of the 30% and 40% treated groups indicated
      significant hypoactivity (adverse effect). This behavioral biomonitoring system
      has proven to be a useful tool to detect sublethal toxicity that could be
      incorporated in biomonitoring protocols in Brazil.

PMID- 17503180
TI  - Genetic influences on anxiety in children: what we've learned and where we're
      heading.
AB  - Anxiety is a common problem, typically beginning early in life. This article
      explores reasons for individual differences in levels of anxiety among children,
      by reviewing the genetic literature. The plethora of research to date has
      demonstrated clearly that both genes and environmental influences play important
      roles in explaining differences in levels of anxiety of various types among
      children. This has encouraged researchers to search for specific genes and
      environmental influences upon anxiety. Despite important progress in identifying
      links between anxiety and specific genes--including associations between
      serotonin and dopamine genes and different symptoms of anxiety--overall, progress
      has been slow because multiple genes of small effect size are likely to influence
      anxiety. This article explains how the hunt for genes involved in anxiety is
      likely to benefit from genetically sensitive research, which examines the co
      occurrence of symptoms; includes measures of the environment; and examines
      endophenotypes and risk pathways.

PMID- 17503181
TI  - 5-aminosalicylic acid improves indomethacin-induced enteropathy by inhibiting
      iNOS transcription in rats.
AB  - Nitric oxide has been implicated in the pathogenic mechanism of inflammatory
      bowel disease states. We evaluated indomethacin-induced enteropathy in rats, in
      relation to the expression of the inducible isoform of NO synthase (iNOS) using
      aminosalicylic acid (5-ASA), its isomer 4-ASA (10 or 50 mg/kg/day, po), and
      dexamethasone, an iNOS transcription inhibitor (3 mg/kg/day, sc). Enteropathy was
      induced by indomethacin (7.5 mg/kg/day, sc) for two days and the small intestine
      was examined for lesions over the next 14 days. Indomethacin-induced small
      intestinal ulcer size, mucosal myeloperoxidase activity, iNOS expression and
      serum nitrite/nitrate levels were maximally increased by day 4 and gradually
      decreased by day 14. Treatment with 5-ASA, but not 4-ASA, decreased indomethacin
      induced ulcer length, myeloperoxidase activity, serum nitrite/nitrate levels and
      iNOS expression at day 4. Dexamethasone had a greater effect than 5-ASA in
      reducing myeloperoxidase activity and ulcer length by 26 and 32%, respectively.
      Dexamethasone also reduced serum nitrate/nitrite and iNOS expression to their
      basal levels. In conclusion, inhibition of iNOS expression by 5-ASA appears to be
      associated with diminished intestinal ulceration in indomethacin-induced
      enteropathy.

PMID- 17503182
TI  - Antidepressant therapy (imipramine and citalopram) for irritable bowel syndrome:
      a double-blind, randomized, placebo-controlled trial.
AB  - BACKGROUND: The efficacy of antidepressants in irritable bowel syndrome (IBS) is
      controversial. No trials have directly compared a tricyclic with a selective
      serotonin reuptake inhibitor. Our aim was to determine whether imipramine and
      citalopram are efficacious in IBS. METHODS: This was a randomized, double-blind,
      placebo-controlled, parallel group pilot trial with imipramine (50 mg) and
      citalopram (40 mg). RESULTS: Of 51 IBS patients randomized, baseline
      characteristics were comparable among the treatment arms; the majority was
      diarrhea-predominant. Adequate relief of IBS symptoms (primary endpoint) was
      similar for each treatment arm. Improvements in bowel symptom severity rating for
      interference (P = 0.05) and distress (P = 0.02) were greater with imipramine
      versus placebo, but improvements in abdominal pain were not. There was a greater
      improvement in depression score (P = 0.08) and in the SF-36 Mental Component
      Score (P = 0.07), with imipramine. Citalopram was not superior to placebo.
      Approximately 20% of the variance in scores was explained by treatment
      differences for abdominal pain, bowel symptom severity disability, depression and
      the mental component of the SF-36. CONCLUSION: Neither imipramine nor citalopram
      significantly improved global IBS endpoints over placebo.

PMID- 17503183
TI  - Korean immigrants' knowledge of heart attack symptoms and risk factors.
AB  - PURPOSE: This study assessed the knowledge of heart attack symptoms and risk
      factors in a convenience sample of Korean immigrants. METHOD: A total of 116
      Korean immigrants in a Midwestern metropolitan area were recruited through Korean
      churches and markets. Knowledge was assessed using both open-ended questions and
      a structured questionnaire. Latent class cluster analysis and Chi-square tests
      were used to analyze the data. RESULTS: About 76% of the sample had at least one
      self-reported risk factor for cardiovascular disease. Using an open-ended
      question, the majority of subjects could only identify one symptom. In the
      structured questionnaire, subjects identified a mean of 5 out of 10 heart attack
      symptoms and a mean of 5 out of 9 heart attack risk factors. Latent class cluster
      analysis showed that subjects clustered into two groups for both risk factors and
      symptoms: a high knowledge group and a low knowledge group. Subjects who
      clustered into the risk factor low knowledge group (48%) were more likely than
      the risk factor high knowledge group to be older than 65 years, to have lower
      education, to not know to use 911 when a heart attack occurred, and to not have a
      family history of heart attack. CONCLUSION: Korean immigrants' knowledge of heart
      attack symptoms and risk factors was variable, ranging from high to very low.
      Education should be focused on those at highest risk for a heart attack, which
      includes the elderly and those with risk factors.

PMID- 17503184
TI  - Intimate partner violence: how does it impact major depressive disorder and post
      traumatic stress disorder among immigrant Latinas?
AB  - Intimate Partner Violence (IPV) is prevalent in the general US population, as
      well as the Latino community. In a cross-sectional study at an immigrant, primary
      care clinic, we assessed the correlation between IPV history and symptoms of MDD
      and PTSD in Latino women. We used a structured interview format. Among the 105
      women recruited, the 4-week incidence of MDD was 45.7% and the prevalence of PTSD
      was 19%. Abused women had three times the odds of meeting PTSD criteria than non
      abused women. Women meeting PTSD criteria were 10 times likelier to also report
      MDD. There was no difference in the incidence of MDD among women who reported IPV
      and those who did not. This study found a correlation of IPV with PTSD, and PTSD
      with MDD, but not IPV with MDD. Our results indicate a need for mental health
      interventions in primary care settings for Latina women regardless of IPV
      history.

PMID- 17503185
TI  - Modeling of size dependent failure in cardiovascular stent struts under tension
      and bending.
AB  - Cardiovascular stents are cylindrical mesh-like metallic structures that are used
      to treat atherosclerosis. The thickness of stent struts are typically in the
      range of 50-150 microm. At this microscopic size scale, the tensile failure
      strain has been shown to be size dependent. Micromechanically representative
      computational models have captured this size effect in tension. In this paper
      polycrystalline models incorporating material fracture are used to investigate
      size effects for realistic stent strut geometries and loading modes. The specific
      loading a stent undergoes during deployment is uniquely captured and the
      implications for stent design are considered. Fracture analysis is also
      performed, identifying trends in terms of strut thickness and loading type. The
      results show, in addition to the size effect in tension, further size effects in
      different loading conditions. The results of the loading analyses are combined to
      produce a tension and bending failure graph. This design safety diagram is
      presented as a tool to predict failure of stent struts. This study is
      particularly significant given the current interest in producing smaller stents.

PMID- 17503186
TI  - Large-scale optimization-based classification models in medicine and biology.
AB  - We present novel optimization-based classification models that are general
      purpose and suitable for developing predictive rules for large heterogeneous
      biological and medical data sets. Our predictive model simultaneously
      incorporates (1) the ability to classify any number of distinct groups; (2) the
      ability to incorporate heterogeneous types of attributes as input; (3) a high
      dimensional data transformation that eliminates noise and errors in biological
      data; (4) the ability to incorporate constraints to limit the rate of
      misclassification, and a reserved-judgment region that provides a safeguard
      against over-training (which tends to lead to high misclassification rates from
      the resulting predictive rule); and (5) successive multi-stage classification
      capability to handle data points placed in the reserved-judgment region. To
      illustrate the power and flexibility of the classification model and solution
      engine, and its multi-group prediction capability, application of the predictive
      model to a broad class of biological and medical problems is described.
      Applications include: the differential diagnosis of the type of erythemato
      squamous diseases; predicting presence/absence of heart disease; genomic analysis
      and prediction of aberrant CpG island meythlation in human cancer; discriminant
      analysis of motility and morphology data in human lung carcinoma; prediction of
      ultrasonic cell disruption for drug delivery; identification of tumor shape and
      volume in treatment of sarcoma; discriminant analysis of biomarkers for
      prediction of early atherosclerois; fingerprinting of native and angiogenic
      microvascular networks for early diagnosis of diabetes, aging, macular degeneracy
      and tumor metastasis; prediction of protein localization sites; and pattern
      recognition of satellite images in classification of soil types. In all these
      applications, the predictive model yields correct classification rates ranging
      from 80 to 100%. This provides motivation for pursuing its use as a medical
      diagnostic, monitoring and decision-making tool.

PMID- 17503187
TI  - A qualitative study of programs for parents with serious mental illness and their
      children: building practice-based evidence.
AB  - The rationale for the development of effective programs for parents with serious
      mental illness and their children is compelling. Using qualitative methods and a
      grounded theory approach with data obtained in site visits, seven existing
      programs for parents with mental illness and their children in the United States
      are described and compared across core components: target population, theory and
      assumptions, funding, community and agency contexts, essential services and
      intervention strategies, moderators, and outcomes. The diversity across programs
      is strongly complemented by shared characteristics, the identification of which
      provides the foundation for future testing and the development of an evidence
      base. Challenges in program implementation and sustainability are identified.
      Qualitative methods are useful, particularly when studying existing programs, in
      taking steps toward building the evidence base for effective programs for parents
      with serious mental illness and their children.

PMID- 17503188
TI  - Membrane organization of the serotonin 1A receptor monitored by a detergent-free
      approach.
AB  - : 1. Insolubility of membrane constituents in nonionic detergents such as Triton
      X-100 has been a widely used biochemical criterion to indicate their localization
      in membrane domains. However, concerns on the possibility of membrane
      perturbation in the presence of detergents have led to the development of
      detergent-free approaches.2. We have explored the organization of the
      serotonin(1A) receptor, an important G-protein coupled receptor, from bovine
      hippocampus and CHO cells using a detergent-free approach in order to address the
      points of agreement with our previous results using Triton X-100.3. A significant
      fraction of the serotonin(1A) receptor has been found to be localized in a heavy
      density fraction obtained using a detergent-free approach to isolate membrane
      domains. In addition, we have characterized the membrane fractions isolated in
      terms of their lipid composition and membrane physical properties.4. The results
      obtained on the membrane localization of the serotonin(1A) receptor from the
      present experiments using a detergent-free approach correlate well with our
      earlier findings obtained using a detergent-based method (Kalipatnapu, S., and
      Chattopadhyay, A., FEBS Lett. 576:455-460, 2004). These results provide important
      information on the membrane organization of the hippocampal serotonin(1A)
      receptor and are relevant in view of the concerns on the use of detergent in
      determination of membrane organization of constituent proteins and lipids.

PMID- 17503189
TI  - Calculations of protein-ligand binding entropy of relative and overall molecular
      motions.
AB  - In the context of virtual database screening, calculations of protein-ligand
      binding entropy of relative and overall molecular motions are challenging, owing
      to the inherent structural complexity of the ligand binding well in the energy
      landscape of protein-ligand interactions and computing time limitations. We
      describe a fast statistical thermodynamic method for estimation the binding
      entropy to address the challenges. The method is based on the integration of the
      configurational integral over clusters obtained from multiple docked positions.
      We apply the method in conjunction with 11 popular scoring functions (AutoDock,
      ChemScore, DrugScore, D-Score, F-Score, G-Score, LigScore, LUDI, PLP, PMF, X
      Score) to evaluate the binding entropy of 100 protein-ligand complexes. The
      averaged values of binding entropy contribution vary from 6.2 to 9.1 kcal/mol,
      showing good agreement with literature. We calculate positional sizes and the
      angular volume of the native ligand wells. The averaged geometric mean of
      positional sizes in principal directions varies from 0.8 to 1.4 A. The calculated
      range of angular volumes is 3.3-11.8 rad(2). Then we demonstrate that the
      averaged six-dimensional volume of the native well is larger than the volume of
      the most populated non-native well in energy landscapes described by all of 11
      scoring functions.

PMID- 17503190
TI  - Comparative population structure of Chinese sumac aphid Schlechtendalia chinensis
      and its primary host-plant Rhus chinensis.
AB  - Most of our current understanding of comparative population structure has been
      come from studies of parasite-host systems, whereas the genetic comparison of
      gallnut-aphids and their host-plants remain poorly documented. Here, we examined
      the population genetic structure of the Chinese sumac aphid Schlechtendalia
      chinensis and its unique primary host-plant Rhus chinensis in a mountainous
      province in western China using inter-simple sequence repeat (ISSR) markers.
      Despite being sampled from a mountainous geographic range, analysis of molecular
      variance (AMOVA) showed that the majority of genetic variation occurred among
      individuals within populations of both the aphid and its host. The aphid
      populations were found to be structured similarly to their primary host
      populations (F (ST) values were 0.239 for the aphid and 0.209 for its host),
      suggesting that there are similar patterns of gene flow between the populations
      of the aphid and between populations of its host-plant. The genetic distances (F
      (ST)/1 - F (ST)) between the aphid populations and between its host-plant
      populations were uncorrelated, indicating that sites with genetically similar
      host-plant populations may not always have genetically similar aphid populations.
      The lack of relationships between genetic and geographical distance matrices
      suggested that isolation by distance (IBD) played a negligible role at this
      level. This may be mainly attributed to the founder effect, genetic drift and the
      relative small spatial scale between populations.

PMID- 17503191
TI  - Duplicated Clock genes with unique polyglutamine domains provide evidence for
      nonhomologous recombination in Chinook salmon (Oncorhynchus tshawytscha).
AB  - Circadian rhythms underlie diverse life functions ranging from cellular
      activities to behavior. Multiple clock genes play a central role in the
      generation of these rhythms. We partially characterized two copies of the Clock
      gene from Chinook salmon (Oncorhynchus tshawytscha), OtsClock1a and OtsClock1b.
      The 6,460 bp OtsClock1a sequence contains 16 exons, 15 introns and encompasses
      three highly conserved domains indicating it is a novel member of the bHLH-PAS
      superfamily of transcription factors. The second copy, OtsClock1b, consists of
      five exons and five introns spanning 1,945 bp. A polyglutamine repeat motif
      (PolyQ), characteristic of a majority of CLOCK proteins, is present in both
      OTSCLOCK1a and OTSCLOCK1b. However, the Chinook PolyQ domains are uniquely
      positioned inside the gene. Interestingly, a 1,200 bp non-coding segment located
      downstream of the OtsClock1a PolyQ domain is absent from OtsClock1b. This
      insertion/deletion is 91% similar to the Salmo salar Transferrin gene. A
      phylogenetic analysis of 11 CLOCK proteins shows that OtsClock1a and OtsClock1b
      are paralogs which likely arose subsequent to the salmonid genome-wide
      duplication event. Ultimately, the Chinook salmon Clock genes are key components
      to our understanding the genetic mechanisms underlying temporally regulated life
      history traits in Pacific salmonids.

PMID- 17503192
TI  - Impact of submersible pumps on Pb constituents in residential wells.
AB  - Dissolved Pb in 51 domestic wells screened from 18 to 48 m in glacial tills and
      outwash deposits were examined in conjunction with the characteristics of their
      corresponding submersible pump. Pb concentrations, ranging from 0.8 to 24.9
      microg l(-1), entering residential water supplies were measured during 2001-2004
      in the Royal watershed, Maine. Principal component analyses assisted the
      weighting of pump age, well screen depth, and draw time variables. Preliminary Pb
      sequestration significance in the boreholes was predicted from geochemical
      speciation and synchrotron XAS analyses. Nascent 207Pb/206Pb and 208Pb/206Pb
      isotope analyses assisted the discrimination of possibly leached Pb from
      submersible pump materials among geogenic sources.

PMID- 17503193
TI  - Microglial activation in different models of peripheral nerve injury of the rat.
AB  - Pain and pain modulation has been viewed as being mediated entirely by neurons.
      However, new research implicates spinal cord glia as key players in the creation
      and maintenance of pathological pain. Sciatic nerve lesions are one of the most
      commonly studied pain-related injuries. In our study we aimed to characterize
      changes in microglial activation in the rat spinal cord after axotomy and chronic
      constriction injury of the sciatic nerve and to evaluate this activation in
      regard to pain behavior in injured and control groups of rats. Microglial
      activation was observed at ipsilateral side of lumbar spinal cord in all
      experimental groups. There were slight differences in the level and extent of
      microglial activation between nerve injury models used, however, differences were
      clear between nerve-injured and sham animals in accordance with different level
      of pain behavior in these groups. It is known that activated microglia release
      various chemical mediators that can excite pain-responsive neurons. Robust
      microglial activation observed in present study could therefore contribute to
      pathological pain states observed following nerve injury.

PMID- 17503194
TI  - Tissue expression and cellular localization of phospholipid hydroperoxide
      glutathione peroxidase (PHGPx) mRNA in male mice.
AB  - Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is an ubiquitous
      antioxidant enzyme, but the exact expression pattern in mammalian tissues is
      still unknown. The expression and cellular localization of PHGPx mRNA were
      examined in male mice using real time-polymerase chain reaction and in situ
      hybridization techniques. The rank order of PHGPx mRNA expression across tissues
      exhibiting substantial levels of expression was:testes >> heart > cerebrum > or =
      ileum > stomach = liver = jejunum > or = epididymis. In testes, PHGPx mRNA was
      highly expressed in spermiogenic cells and Leydig cells. The signal was also
      expressed in the molecular layer, Purkinje cell layer, and white matter of
      cerebellum, the pituicytes of neurohypophysis, the parafollicular cells and
      follicular basement membrane of thyroid, the exocrine portion of pancreas, the
      tubular epithelium of kidney, the smooth muscle cells of arteries, and the red
      pulp of spleen. In the gastrointestinal tract, PHGPx mRNA expression was mainly
      observed in the keratinized surface epithelium of forestomach, the submucosal
      glands and serosa layers, and further the Paneth cells of intestines. PHGPx mRNA
      appeared to be ubiquitously expressed in the parenchyma of heart, liver, and
      lung. These results indicate that PHGPx exhibits a cell- and tissue-specific
      expression pattern in mice.

PMID- 17503196
TI  - Assessing the feasibility of wastewater recycling and treatment efficiency of
      wastewater treatment units.
AB  - Wastewater reuse can significantly reduce environmental pollution and save the
      water sources. The study selected Cheng-Ching Lake water treatment plant in
      southern Taiwan to discuss the feasibility of wastewater recycling and treatment
      efficiency of wastewater treatment units. The treatment units of this plant
      include wastewater basin, sedimentation basin, sludge thickener and sludge
      dewatering facility. In this study, the treatment efficiency of SS and turbidity
      were 48.35-99.68% and 24.15-99.36%, respectively, showing the significant removal
      efficiency of the wastewater process. However, the removal efficiencies of NH(3)
      N, total organic carbon (TOC) and chemical oxygen demand (COD) are limited by
      wastewater treatment processes. Because NH(3)-N, TOC and COD of the mixing
      supernatant and raw water are regulated raw water quality standards, supernatant
      reuse is feasible and workable during wastewater processes at this plant.
      Overall, analytical results indicated that supernatant reuse is feasible.

PMID- 17503197
TI  - Trends in exhaust emissions from in-use Mexico City vehicles, 2000-2006. A remote
      sensing study.
AB  - A remote sensing study was conducted in year 2006 in four locations of the
      Metropolitan Area of Mexico City (MAMC). Two of the sites were the same studied
      back by us in year 2000 and by others in year 1994. A database was compiled
      containing 11,289 valid measurements for the carbon monoxide (CO), total
      hydrocarbons (THC), and nitric oxide (NO) exhaust vehicles emissions. Valid
      measurements were binned for each pollutant by the vehicle specific power
      (between -5 and 20 kW tonne(-1)) for the 2000 and 2006 databases. The mean
      average CO, THC, and NO emissions for year 2006 were determined to be 1.10 +/-
      0.18 vol.%, 299 +/- 88.4 ppm, and 610 +/- 115.0 ppm, respectively. Matching the
      vehicle driving patterns of the fleet measured in year 2000 with the emissions
      factors obtained in this work, allows estimating the trends in the exhaust
      emissions of vehicles in the MAMC. The adjusted results of the remote sensing
      study performed in year 2006 shows that the fleet has decrease 22% in CO and 17%
      in NO emissions, with small change in total hydrocarbons emissions. The
      improvements could be related with the introduction in year 2001 of vehicles that
      met tighter emissions standards, particularly for nitrogen oxides.

PMID- 17503198
TI  - Monitoring of ambient particles and heavy metals in a residential area of Seoul,
      Korea.
AB  - In this study, ambient TSP, PM10, and PM2.5 in a residential area located in the
      northern part of Seoul were monitored every other month for 1 year from April
      2005 to February 2006. The monthly average levels of TSP, PM10, and PM2.5 had
      ranges of 71 approximately 158, 40 approximately 106, and 28 approximately 43
      microg/m(3), respectively. TSP and PM10 showed highest concentration in April;
      this seems to be due to Asian dust from China and/or Mongolia. However, the fine
      particle of PM2.5 showed a relatively constant level during the monitoring
      period. Heavy metals in PM 10 and PM2.5, such as Cr, As, Cd, Mn, Zn and Pb, were
      also analysed during the same period. The monthly average concentrations of heavy
      metal in PM2.5 were Cr:1.9 approximately 22.7 ng/m(3); As:0.9 approximately 2.5
      ng/m(3); Cd: 0.6 approximately 7 ng/m(3); Mn:6.1 approximately 22.6 ng/m(3); Zn:
      38.9 approximately 204.8 ng/m(3), and Pb: 21.6 approximately 201.1 ng/m(3). For
      the health risk assessment of heavy metals in ambient particles, excess cancer
      risks were calculated using IRIS unit risk. As a result, the excess cancer risks
      of chromium, cadmium, and arsenic were shown to be more than one per million
      based on the annual concentration of heavy metals, and chromium showed the
      highest excess cancer risk in ambient particles in Seoul.

PMID- 17503199
TI  - Residues of organochlorine pesticides in water and suspended particulate matter
      from the Yangtze River catchment of Wuhan, China.
AB  - The residues of 13 organochlorine pesticides (OCPs) in surface water and HCHs and
      DDTs in suspended particulate matter (SPM) from rivers and lakes in Yangtze River
      catchment of Wuhan, China, were investigated. The concentration of total OCPs in
      surface water varied from 1.01 to 46.49 ng l(-1) (mean 10.55 ng l(-1)). The
      levels of total HCHs (SigmaHCH) and total DDTs (SigmaDDT) in surface water were
      in the range of 0.55-28.07 ng l(-1) and lower than detection limit to 16.71 ng l(
      1), respectively, which was lower than Chinese standards on the whole. For OCPs
      residues in SPM, the mean levels varying from 0.20 to 34.72 ng l(-1) and 0.46 to
      2.72 ng l(-1) for SigmaHCH and SigmaDDT, respectively, which ranked the
      relatively higher levels among Chinese studied rivers. Results from this
      investigation showed that previous excessive usage of technical OCPs was the main
      reason for the residues of HCHs and DDTs both in surface water and SPM, although
      some new sources were likely to occurred in the region. Apart from the OCPs in
      SPM originated from upstream in flood season, one of the important sources of OCP
      residues both in water and SPM in Yangtze River was supposed to be the inputs of
      its tributaries. Additionally, in situ water-SPM phase distributions of OCPs
      indicated that HCHs tended to transport (correction of totransport) with water as
      well as DDTs was prone to combine with SPM in Yangtze River catchment of Wuhan.

PMID- 17503200
TI  - Seasonal variations of heavy metals in some organs of carp (Cyprinus carpio L.,
      1758) from Beysehir Lake (Turkey).
AB  - In this study which was carried out between March 2003 and February 2005 Fe, Cu,
      Zn, Mn, Cr, Pb and Cd contents were determined in muscle, liver and gill of carp
      (Cyprinus carpio L., 1758) caught from Beysehir Lake. Among the heavy metals
      analyzed Cr, Pb and Cd were below the detection limit (<0.03). Heavy metal
      concentrations varied significantly depending on the type of the tissue and
      season. The highest metal concentrations were found in the liver, followed by
      gill and muscle. Heavy metal levels in tissues of carp were increased in summer
      and winter, while were decreased in autumn and spring. The present study shows
      that precautions need to be taken in Beysehir Lake in order to prevent heavy
      metal pollution that can occur in the future.

PMID- 17503201
TI  - Spatiotemporal distribution of arsenic species of oysters (Crassostrea gigas) in
      the coastal area of southwestern Taiwan.
AB  - This study investigated total arsenic (As) and As species contents of oysters
      (Crassostrea gigas) in different production areas, seasons and sea locations on
      the southwestern coast of Taiwan. Analytical results indicate that contents of
      total As, arsenite, arsenate, dimethylarsinic acid, monomethylarsonic acid and
      arsenobetaine in oysters are 9.90+/-3.68, 0.091+/-0.104, 0.033+/-0.038, 0.529+/
      0.284, 0.037+/-0.046 and 3.94+/-1.33 mg/g (dry wt), respectively. A ratio of
      inorganic As concentrations to total As concentrations is 1.26%. Total As
      contents of oysters cultured in the outer sea are statistically significantly
      lower than those of oysters cultured in the inner sea. The total As contents of
      oysters is the highest in Putai, where the blackfoot disease prevails. The low As
      contents in oysters is attributed to the low temperature in winter, which slows
      the metabolism of oysters. A maximum value is 33.37 microg/g (dry) in Putai in
      spring, because a considerable amount of aquacultural waste water with high As
      contents is discharged into adjacent drainage channels and rivers there during
      that season.

PMID- 17503202
TI  - Attenuation of N2O emission rates from agricultural soil at different
      dicyandiamide concentrations.
AB  - An experiment was conducted to assess the role of different concentrations of
      dicyandiamide (DCD), a potent nitrification inhibitor, on temporal changes in
      nitrous oxide emission from sandy loam agricultural soil. It was found that with
      increasing concentration of DCD i.e. from 6 to 12% of nitrogen applied in the
      form of urea, there was a decrease in the both average and peak N(2)O emissions.
      However, from 14% DCD treated soil, there was a non-significant alteration in the
      N(2)O emission. Maximum average N(2)O efflux of 217.55 microg m(-2) h(-1) was
      noted from control plots. As compared to control, there was an attenuation of 50,
      58, 65, and 91% average N(2)O efflux from 6, 8, 10 and 12% DCD applied pots,
      respectively, whereas, there was a negative average of N(2)O efflux from the soil
      with 14% DCD treatment. The soil N content also showed a significant correlation
      with N(2)O emission. Therefore, 12% DCD treatment has been found to be the best
      with regard to attenuation of nitrous oxide from sandy loam agricultural soils.

PMID- 17503203
TI  - Assessment of river water quality during snowmelt and base flow periods in two
      catchment areas with different land use.
AB  - River water quality was evaluated with respect to eutrophication and land use
      during spring snowmelt and summer base flow periods in Abashiri (mixed cropland
      livestock farming) and Okoppe (grassland-based dairy cattle farming), eastern
      Hokkaido, Japan. Water from rivers and tributaries was sampled during snowmelt
      and summer base flow periods in 2005, and river flow was measured. Total N (TN),
      NO(3)-N, and Si concentrations were determined using standard methods. Total
      catchment and upland areas for each sampling site were determined with ArcGIS
      hydrology modeling software and 1:25,000-scale digital topographic maps. Specific
      discharge was significantly higher during snowmelt than during base flow. In both
      areas, TN concentrations increased, whereas Si concentrations decreased, with
      increased specific discharge, and were significantly higher during snowmelt. The
      Si:TN mole ratio decreased to below or close to the threshold value for
      eutrophication (2.7) in one-third of sites during snowmelt. River NO(3)-N
      concentrations during base flow were significantly and positively correlated with
      the proportion of upland fields in the catchment in both the Abashiri (r = 0.88,
      P < 0.001) and Okoppe (r = 0.43, P < 0.01) areas. However, the regression slope,
      defined as the impact factor (IF) of water quality, was much higher in Abashiri
      (0.025) than in Okoppe (0.0094). The correlations were also significantly
      positive during snowmelt in both areas, but IF was four to eight times higher
      during snowmelt than during base flow. Higher discharge of N from upland fields
      and grasslands during snowmelt and the resulting eutrophication in estuaries
      suggest that nutrient discharge during snowmelt should be taken into account when
      assessing and monitoring the annual loss of nutrients from agricultural fields.

PMID- 17503204
TI  - Which group is best? Attributes of different biological assemblages used in
      freshwater biomonitoring programs.
AB  - Of the many groups of organisms proposed for use in biomonitoring, assemblages of
      fish, algae, and benthic macroinvertebrates are the most commonly selected.
      Purported advantages and disadvantages of using these groups, along with those of
      zooplankton, were assembled from 65 different publications and websites. From
      these, 13 categories of advantages and nine of disadvantages were created. The
      diversity of the assemblage and its importance to the ecosystem were reported as
      advantages in >20% of citations for each group; these similarities suggest that
      some redundancy exists among the different groups in terms of these features.
      Likewise, sampling difficulties and lack of analytic metrics were disadvantages
      listed in >20% of citations for each group. Few reported advantages (e.g.
      recreational value of fish) or disadvantages (e.g. short generation time of
      algae) were unique for a particular assemblage. The validity of reported
      advantages and disadvantages were sometimes region specific, other times
      incorrect. The choice of which assemblage is most appropriate for a biomonitoring
      program ultimately depends on the characteristics of the area to be studied and
      the program objectives.

PMID- 17503205
TI  - Quantifying coastal inundation vulnerability of Turkey to sea-level rise.
AB  - The vulnerability of low-lying coastal areas in Turkey to inundation was
      quantified based on the sea-level rise scenarios of 1, 2, and 3 m by 2205.
      Through digital elevation model (DEM) acquired by the shuttle radar topography
      mission (SRTM), the extent and distribution of the high to low-risk coastal
      plains were identified. The spatio-temporal analysis revealed the inundated
      coastal areas of 545, 1,286, and 2,125 km2 at average rates of 5, 10, and 15 mm
      yr(-1) for 200 years, respectively. This is equivalent to minimum and maximum
      land losses by 2205 of 0.1-0.3% of the total area and of 1.3-5.2% of the coastal
      areas with elevations of less than 100 m in the country, respectively. This study
      provides an initial assessment of vulnerability to sea-level rise to help
      decision-makers, and other concerned stakeholders to develop appropriate public
      policies and land-use planning measures.

PMID- 17503206
TI  - Assessment of microcystins in lake water and the omnivorous fish (Carassius
      gibelio, Bloch) in Lake Pamvotis (Greece) containing dense cyanobacterial bloom.
AB  - Toxin-producing cyanobacteria in lakes and reservoirs form a threat to humans as
      well as various forms of aquatic life. This study examined the occurrence and
      distribution of Microcystins (MCYST) in the shallow eutrophic lake Pamvotis
      (Greece). MCYST concentrations in the tissues (liver, kidneys, intestine, gonads,
      brain and muscle) of the fish species Carassius gibelio were also examined. Tests
      were performed with an enzyme-linked immunosorbent assay (ELISA). MCYST
      concentration in water and in the scum of Lake Pamvotis were highest during the
      warm period (April-October, 2005). Phytoplankton samples were dominated by the
      genera Microcystis and Anabaena during the same period. MCYST values were always
      below the WHO Guide level for recreational waters but much higher than the WHO
      Guide level for drinking water. It was found that MCYST can accumulate in the
      fish tissues of C. gibelio. Even though the target organ for MCYST is the liver,
      in our study MCYST were found also in the rest of C. gibelio tissues in the
      following order: intestine> kidney> > brain>gonads> muscle. Muscle tissue
      contained concentrations of microcystins that correspond to 0.096 microg/kg/day
      well above the recommended limit for human consumption (0.04 microg/Kg/day).

PMID- 17503207
TI  - Persistence and vertical distribution of termiticide fipronil in modified ground
      board test.
AB  - Fipronil termiticide belongs to phenyl-pyrazole class of chemical compounds. It
      has broad-spectrum activity particularly against house hold pests such as
      cockroaches, mosquitoes, locusts, ticks, and fleas at both larval and adult
      stages. At high dosage it can be used to control subterranean termites in
      building foundations. To evaluate long term efficacy against termites the
      persistence and vertical distribution of fipronil was studied under natural
      weather conditions of Dehradun, India. Fipronil was applied at four
      concentrations i.e. 0.05, 0.1, 0.25 and 0.5% a.i ha(-1) by drenching 17 x 17
      in.(2) plot prepared as per modified ground board test. Soil samples were
      collected after 22, 38 and 56 months of treatment up to the depth of 75 cm. The
      soil core was cut into five distinct sections i.e. 0-15, 15-30, 30-45, 45-60 and
      60-75 cm depth. The residues were extracted by shaking 20 g soil sample with
      acetone. The acetone extract was concentrated and cleaned-up over florisil
      column. Fipronil residues were estimated on GLC at 220, 260, and 300 degrees C
      oven, injector and detector temperature respectively. Fipronil was found to
      persist beyond 56 months after application. Two metabolites viz. desulfinyl and
      sulfide-fipronil were detected in sampling after 22 months of application that
      also dissipated with time. Fipronil residues were found up to 60 cm depth. The
      residues in deeper layers dissipate slowly with time and after 56 months of
      treatment residues were detected only up to 30 cm depth.

PMID- 17503209
TI  - Resource recovery potential from secondary components of segregated municipal
      solid wastes.
AB  - Fermentable components of municipal solid wastes (MSW) such as fruit and
      vegetable wastes (FVW), leaf litter, paddy straw, cane bagasse, cane trash and
      paper are generated in large quantities at various pockets of the city. These
      form potential feedstocks for decentralized biogas plants to be operated in the
      vicinity. We characterized the fermentation potential of six of the above MSW
      fractions for their suitability to be converted to biogas and anaerobic compost
      using the solid-state stratified bed (SSB) process in a laboratory study. FVW and
      leaf litter (paper mulberry leaves) decomposed almost completely while paddy
      straw, sugarcane trash, sugarcane bagasse and photocopying paper decomposed to a
      lower extent. In the SSB process between 50-60% of the biological methane
      potential (BMP) could be realized. Observations revealed that the SSB process
      needs to be adapted differently for each of the feedstocks to obtain a higher gas
      recovery. Bagasse produced the largest fraction of anaerobic compost
      (fermentation residue) and has the potential for reuse in many ways.

PMID- 17503208
TI  - Inorganic constituents of urban air pollution in the Lazio region (Central
      Italy).
AB  - A field study was carried out at six locations in the Lazio region (Central
      Italy) aimed at characterising atmospheric particulate matter (PM10 and PM2.5)
      from the point of view of the chemical composition and grain size distribution of
      the particles, the mixing properties of the atmosphere, the frequency and
      relevance of natural events. The combination of four different analytical
      techniques (ion chromatography, X-ray fluorescence and ICP for inorganic
      components, thermo-optical analysis for carbon compounds) yielded sound results
      in terms of characterisation of the air masses. During the first three months of
      the study (October-December 2004), many pollution events of natural (sea-salt or
      desert dust episodes) or anthropogenic nature were identified and characterised.
      More than 90% of the collected mass was identified by chemical analysis. The
      central role played by the mixing properties of the lower atmosphere when
      pollution events occurred was highlighted. The results show a major impact of
      primary anthropogenic pollutants on traffic stations and a homogeneous
      distribution of secondary pollutants over the regional area. An evaluation of the
      sources of PM and an identification of possible reliable tracers were obtained
      using a chemical fractionation procedure.

PMID- 17503210
TI  - Micro-treatment options for components of organic fraction of MSW in residential
      areas.
AB  - There is a growing interest in management of MSW through micro-treatment of
      organic fraction of municipal solid wastes (OFMSW) in many cities of India. The
      OFMSW fraction is high (>80%) in many pockets within South Indian cities like
      Bangalore, Chikkamagalur, etc. and is largely represented by vegetable, fruit,
      packing and garden wastes. Among these, the last three have shown problems for
      easy decomposition. Fruit wastes are characterized by a large pectin supported
      fraction that decomposes quickly to organic acids (becomes pulpy) that eventually
      slow down anaerobic and aerobic decomposition processes. Paper fraction
      (newsprint and photocopying paper) as well as paddy straw (packing), bagasse
      (from cane juice stalls) and tree leaf litter (typical garden waste and street
      sweepings) are found in reasonably large proportions in MSW. These decompose
      slowly due to poor nutrients or physical state. We have examined the suitability
      of these substrates for micro-composting in plastic bins by tracking
      decomposition pattern and physical changes. It was found that fruit wastes
      decompose rapidly to produce organic acids and large leachate fraction such that
      it may need to be mixed with leachate absorbing materials (dry wastes) for good
      composting. Leaf litter, paddy straw and bagasse decompose to the tune of 90, 68
      and 60% VS and are suitable for composting micro-treatment. Paper fractions even
      when augmented with 10% leaf compost failed to show appreciable decomposition in
      50 days. All these feedstocks were found to have good biological methane
      potential (BMP) and showed promise for conversion to biogas under a mixed feed
      operation. Suitability of this approach was verified by operating a plug-flow
      type anaerobic digester where only leaf litter gathered nearby (as street
      sweepings) was used as feedstock. Here only a third of the BMP was realized at
      this scale (0.18 m(3 )biogas/kg VS 0.55 m(3)/kg in BMP). We conclude that
      anaerobic digestion in plug-flow like digesters appear a more suitable micro
      treatment option (2-10 kg VS/day) because in addition to compost it also produces
      biogas for domestic use nearby.

PMID- 17503211
TI  - Monitoring quantity and characteristics of municipal solid waste in Dhaka City.
AB  - A reliable estimate of the quantity of solid waste generation in the city is very
      important for proper solid waste planning and management. However, reported
      estimates of solid waste generation vary widely and lead to questionability. The
      reported values have been derived on the assumption of demography, standard rate
      of waste generation by households, density values, number of trucks engaged for
      waste transportation and monitoring of truck movement at dump sites, etc. This
      diverse nature of the available data and the question of accuracy necessitate a
      rigorous study that has tried to document the waste quantity in the recently
      formulated master plan of Dhaka City. The socio-economic parameters, behavioral
      characteristics, generation sources, seasonality, and per capita growth rate are
      considered in estimating the waste quantity along with its future projections.
      The findings from the estimation of waste quantities state that seasonal
      differences in the municipal solid waste stream are not substantial. The most
      seasonably variable material in the municipal solid waste stream is food waste.
      Residential waste is relatively homogeneous. Although there are some differences
      in waste generation depending on demographic and other local factors, most
      households dispose of essentially similar types of wastes. Variation occurs in
      waste composition dependent upon income levels and category of sources. Variation
      also occurs based upon the extent of source reduction and recycling
      opportunities. As opportunities exist to recycle wastes, the recycling facilities
      might have to grow at a similar pace to the generation of waste. Physical and
      chemical characteristics of solid waste are important to implement the waste
      disposal and management plan for the selection of resource and energy recovery
      potentials. A number of studies have been conducted to determine the composition
      of wastes including moisture content and calorific value. The data show that the
      moisture content in city waste is significantly higher and the calorific value is
      much lower, which determines the viability of composting or anaerobic digestions
      rather than waste combustion.

PMID- 17503212
TI  - The composition, trend and impact of urban solid waste in Beijing.
AB  - This paper provides an overview of the trend of generation, composition, and
      management of municipal solid waste, and estimates the carbon emissions arising
      from municipal solid waste management in Beijing. The correlation analysis
      conducted shows that the generation of municipal solid waste in Beijing has been
      growing steadily, showing high correlations (r > 0.9) to the total GDP, per
      capita income, and the population. Food waste showed an increasing trend since
      1990. Compared with the results of an investigation in 1990, ash and woodchips
      content in 2003 declined from 56% to 17%, while the percentage of paper and
      plastic increased from 10% to 29% over the same period. The calorific value of
      the municipal waste also increased, from 2,686 kJ/kg in 1990 to 4,667 kJ/kg in
      2003, indicating that the waste is suitable for incineration. Currently, the
      source separation ratio of municipal waste is approximately 15%. About 94% of all
      the collected solid waste goes to the landfill while 4% is composted and 2% is
      incinerated. A moderate garbage collection fee is applied to both permanent and
      temporary residents in Beijing, but the willingness to pay for solid waste
      collection and treatment is still low. Under current treatment mode, the total
      amounts of carbon emission from waste disposal sites and incineration increased
      with the increase of municipal solid waste, from 29.8 Gg in 1990 to 84.5 Gg in
      2003, including 83.3 Gg of CH(4) and 22.0 Gg of CO(2). The data availability and
      methodological challenges in monitoring the quantity and characteristics of
      municipal solid waste are discussed.

PMID- 17503213
TI  - Deficit analysis: service capacity assessment and planning in developing
      countries - case study in the Philippines.
AB  - Current demand analysis methods do not formally cover the case of chronic
      deficits in quantity or quality of water and sanitation services. These services
      include drinking water supply (DWS), wastewater and sewage treatment (WST), and
      municipal solid waste management (MSW). Formal analysis of this case would, at
      minimum, define the deficit state and evaluate appropriate options for reducing
      it. This paper proposes for a formal analytical model for municipal sanitation
      systems (MSS) that operate with deficits in at least one of the constituent
      services of DWS, WST, or MSW. The model introduces definitions and notation for
      describing the deficit state for conducting demand analysis on municipal
      sanitation systems. This model of demand analysis for systems with chronic
      deficits will hereinafter be referred to as deficit analysis. A case study for
      Bacoor, Philippines is presented as an example.

PMID- 17503214
TI  - Pilot-study on GIS-based risk modelling of a climate warming induced tertian
      malaria outbreak in Lower Saxony (Germany).
AB  - The area under investigation, Lower Saxony (Northwest Germany), is a former
      malaria region with highest incidences along the coastal zones. Malaria had
      finally become extinct in the early 1950s. Subsequently, further scientific
      investigations in that field declined. Nevertheless, the vector in shape of
      Anopheles mosquitoes has still been present in Lower Saxony. Thus, the question
      arises, whether a new autochthon transmission could take place if the pathogen is
      introduced again and could develop in Anopheles mosquitoes. Answering this
      question was the first aim of the investigation at hand. The second one was to
      examine the spatial and temporal structure of potential transmissions in respect
      to the predicted increase of air temperatures according to the IPCC scenarios. To
      answer these questions, current information about Anophelinae and their
      distribution and habitat preferences within Germany were collected by literature
      research as well as temperature measurements and Anopheles findings were compiled
      from the German Weather Survey and the Niedersachsisches Landesamt fur Okologie
      (NLO), respectively. The results reveal a climate warming between the 30-years
      period from 1961 to 1990 and the years between 1985 and 2004. Induced by higher
      monthly mean temperatures, the risk of a malaria tertiana transmission is
      consequently increasing for Lower Saxony as temperature is the determining
      variable of the mathematical model. The study could demonstrate that most parts
      of the country are located within a 2 months lasting transmission zone. Although
      Germany is not an endemic malaria zone, the pathogen can enter the country most
      likely by infected people or imported mosquitoes that transport it in their guts.

PMID- 17503215
TI  - Pseudo-renal failure due to intraperitoneal bladder rupture and silent subdural
      hematoma following a fall in an alcoholic.
AB  - A middle-aged farmer, presented with progressive abdominal pain and distension,
      an episode of gross hematuria, oligo-anuria following a fall in an alcoholic
      intoxicated state. He was found to have renal failure, and gross ascites, which
      rapidly subsided following continuous bladder catheter drainage. Cystogram
      revealed a tear in the bladder dome, which was repaired. Subsequently, he
      manifested behavioral abnormalities and evaluation revealed right fronto-temporo
      parietal subdural hematoma, which was evacuated through a burr hole. Patient made
      full recovery and was discharged. Intraperitoneal bladder rupture resulting in
      acute pseudo-renal failure is a rare entity. Sudden onset abdominal discomfort,
      increasing ascites, hematuria and oliguria with elevated renal parameters
      following trauma in an alcoholic needs consideration and exclusion of this
      entity. Thus, this case report highlights the importance of intraperitoneal
      rupture of bladder as a cause of pseudo-renal failure. Timely recognition of this
      entity results in easy management and avoidance of inadvertent dialysis.

PMID- 17503217
TI  - The role of coronary CT angiography (CTA) for patients presenting with acute
      chest pain. Defining problem-specific, evidence-based indications of a novel
      imaging modality.
AB  - In the current issue, Stillman et al. (Int J Cardiovasc Imaging, 2007) discuss
      the role of coronary CTA in patients presenting with acute chest pain. The
      authors conclude, that CTA will provide novel information on the presence and
      significance of CAD in patients presenting with acute chest pain. Based on the
      lack of evidence-based data, specific recommendations for its appropriate use are
      incomplete. Most experts agree, that there is the need for large clinical trials
      to determine the accuracy and precision of MDCT for triage of patients with acute
      chest pain.

PMID- 17503216
TI  - Imaging techniques in cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy is a high cost therapeutic option with proven
      efficacy on improving symptoms of ventricular failure and for reducing both
      hospitalization and mortality. However, a significant number of patients do not
      respond to cardiac resynchronization therapy that is due to various reasons.
      Identification of the optimal pacing site is crucial to obtain the best
      therapeutic result that necessitates careful patient selection. Currently, using
      echocardiography for mechanical dyssynchrony assessment performs patient
      selection. Multi-Detector-Row Computed Tomography (MDCT) and Magnetic Resonance
      Imaging (MRI) are new imaging techniques that may assist the cardiologist in
      patient selection. These new imaging techniques have the potential to improve the
      success rate of cardiac resynchronization therapy, due to pre-interventional
      evaluation of the venous coronary anatomy, to evaluation of the presence of scar
      tissue, and to improved evaluation of mechanical dyssynchrony. In conclusion,
      clinical issues associated with heart failure in potential candidates for cardiac
      resynchronization therapy, and the information regarding this therapy that can be
      provided by the imaging techniques echocardiography, MDCT, and MRI, are reviewed.

PMID- 17503218
TI  - Intravascular imaging of atherosclerotic human coronaries in a porcine model: a
      feasibility study.
AB  - OBJECTIVES: To perform intravascular imaging of atherosclerotic human coronary
      conduits in an animal model under conditions of flow and cardiac motion that
      approximate those encountered in vivo. BACKGROUND: Given the lack of animal
      models of vulnerable plaque, a model which would allow imaging of human disease
      and simulate coronary motion and blood flow could advance the development of
      emerging technologies to detect vulnerable plaques. METHODS: Human coronary
      segments from adult cadaver hearts were prepared as xenografts. In anesthetized
      Yorkshire pigs (45-50 kg) the chest was opened and the exposed aorta and right
      atrium were cannulated and attached in an end-to-end fashion to the human
      coronary xenograft, forming an aorto-atrial conduit. The xenograft was fixed to
      the anterior wall of the heart to simulate motion. Angiography and intravascular
      ultrasound (IVUS) of each graft were performed. RESULTS: Twelve human coronary
      grafts (10 from right coronary segments) were prepared and implanted successfully
      in seven animals. All animals tolerated the procedure. The average graft length
      was 39 +/- 2.3 mm. Blood flow rates distal to the graft were >100 ml/min in nine
      grafts. IVUS was performed in all 12 grafts and documented expansion of arterial
      (6.9%) and luminal (9.3%) dimensions during the cardiac cycle (P < 0.001 for
      both). There was a wide range of coronary atherosclerotic pathology within the
      grafts, including intimal thickening, fibrocalcific plaque, and deep lipid pools.
      CONCLUSION: This human-to-porcine coronary xenograft model allows intravascular
      imaging of human coronary pathology under conditions of blood flow and motion,
      and may be used to develop technologies aimed at identifying high-risk plaques.

PMID- 17503219
TI  - Does evidence-based medicine apply to psychiatry?
AB  - Evidence-based psychiatry (EBP) has arisen through the application of evidence
      based medicine (EBM) to psychiatry. However, there may be aspects of psychiatric
      disorders and treatments that do not conform well to the assumptions of EBM. This
      paper reviews the ongoing debate about evidence-based psychiatry and investigates
      the applicability, to psychiatry, of two basic methodological features of EBM:
      prognostic homogeneity of clinical trial groups and quantification of trial
      outcomes. This paper argues that EBM may not be the best way to pursue
      psychiatric knowledge given the particular features of psychiatric disorders and
      their treatments. As a result, psychiatry may have to develop its own standards
      for rigour and validity. This paper concludes that EBM has had a powerful
      influence on how psychiatry investigates and understands mental disorders.
      Psychiatry could influence EBM in return, reshaping it in ways that are more
      clinically useful and congruent with patients' needs.

PMID- 17503220
TI  - Responsiveness to change [corrected] due to supportive-expressive group therapy,
      improvement in mood and disease progression in women with metastatic breast
      cancer.
AB  - OBJECTIVE: To compare the responsiveness of six questionnaires using three
      hypotheses of change: (i) change due to supportive-expressive group therapy
      (SEGT), (ii) improved mood defined as a small effect size (.2) on Profile of Mood
      States (POMS) Total Mood Disturbance score and (iii) progression of disease.
      METHOD: Data from the "Breast Expressive-Supportive Therapy" study, a multicentre
      randomized controlled trial of change due to SEGT versus standard of care in
      women with metastatic breast cancer were used. Questionnaires studied were: POMS,
      Impact of Event Scale, Psychosocial Adjustment to Illness Scale (PAIS), EORTC QLQ
      C30, Mental Adjustment to Cancer and a Pain visual analog scale (VAS).
      Responsiveness to change was evaluated using the standardized response mean. POMS
      was used as the standard. RESULTS: POMS was the most responsive questionnaire to
      change due to SEGT. Questionnaires measuring psychosocial attributes were
      responsive to improvement in mood. EORTC QLQ-C30, PAIS, PAIN VAS and MAC were the
      most responsive to disease progression. More responsive questionnaires were
      associated with the smallest sample size required to detect an effect.
      CONCLUSIONS: Responsiveness to change is context specific. The POMS was the most
      responsive questionnaire to psychosocial therapy.

PMID- 17503221
TI  - Identification and characterization of BH3 domain protein Bim and its isoforms in
      human hepatocellular carcinomas.
AB  - BH3-only protein Bim is a critical regulator of apoptosis and plays an essential
      role in mammalian development, but the characterization of Bim and its isoforms
      in hepatocellular carcinoma (HCC) has not been studied before. Here we
      investigated the expression, distribution, regulation and role of Bim isoforms in
      HCC cells. Fifteen Bim isoforms were identified in HCC, with six newly identified
      isoforms and two newly identified exons. Among of them, Bim EL, L, S, a1, a2, a3,
      b2, b4 and b6 are abundant isoforms according to their mRNA levels. However only
      Bim EL, L and S proteins could be clearly detected. Bim mRNA and protein were
      strongly expressed in HCC tissues compared to relevant non-tumorous regions, but
      the ratio of variant isoforms showed no difference between tumorous and non
      tumorous tissues. Bim isoforms were differentially regulated after
      chemotherapeutic drug 5-Fluorouracil (5-FU) treatment. Interestingly, Bim EL, L
      and S, the isoforms known to induce apoptosis strongly, are the least inducible
      isoforms at their mRNA levels when exposed to the stress, suggesting that post
      transcriptional rather than transcriptional, modulations may play a role to
      enhance their functions. Finally, overexpression of Bim EL, L, S and all alpha
      isoforms induced apoptosis in HCC cells, while overexpression of Bim beta
      isoforms showed no effects on cell survival after 5-FU treatment. In conclusion,
      Bim alpha isoforms appears to have a role in the regulation of apoptosis in HCC
      cells, which may contribute to not only the growth of tumor cells but also the
      sensitivity of HCC cells to chemotherapy.

PMID- 17503222
TI  - Nitric oxide has dual opposite roles during early and late phases of apoptosis in
      cerebellar granule neurons.
AB  - The involvement and the role of nitric oxide (NO) as a signaling molecule in the
      course of neuronal apoptosis, whether unique or modulated during the progression
      of the apoptotic program, has been investigated in a cellular system consisting
      of cerebellar granule cells (CGCs) where apoptosis can be induced by lowering
      extracellular potassium. Several parameters involved in NO signaling pathway,
      such as NO production, neuronal nitric oxide synthase (nNOS) expression, and
      cyclic GMP (cGMP) production were examined in the presence or absence of
      different inhibitors. We provide evidence that nitric oxide has dual and opposite
      effects depending on time after induction of apoptosis. In an early phase, up to
      3 h of apoptosis, nitric oxide supports survival of CGCs through a cGMP-dependent
      mechanism. After 3 h, nNOS expression and activity decreased resulting in shut
      down of NO and cGMP production. Residual NO then contributes to the apoptotic
      process by reacting with rising superoxide anions leading to peroxynitrite
      production and protein inactivation. We conclude that whilst NO over-production
      protects neurons from death in the early phase of neuronal damage, its subsequent
      reduction may contribute to neuronal degeneration and ultimate cell death.

PMID- 17503223
TI  - HSP-70 as a nonspecific early marker in cisplatin ototoxicity.
AB  - CONCLUSION: The great variety of pathological entities related to the presence of
      circulating HSP-70 suggests a nonspecific cellular damage. As the present study
      shows, positive results decrease with respect to the time elapsed after the
      injection of the ototoxic agent. HSP-70 appears as an early and transient marker
      that could permit early detection of inner ear damage. OBJECTIVES: The aim of
      this study was to determine the presence of HSP-70 at different time points by
      means of Western blot immunoassay in the sera of rats treated with cisplatin.
      MATERIALS AND METHODS: Thirty-six Wistar rats were intraperitoneally injected
      with cisplatin at a dose of 5 mg/kg and blood samples were collected at 7 and 90
      days. Determination of HSP-70 was made by means of a modified Western blot
      immunoassay kit originally used for human HSP-70 antigen detection. A control
      group of 18 animals was used for comparison. RESULTS: Western blot was positive
      in 77.8% of the animals in the 7 days group, decreasing to a 44.4% in the 90 days
      group. In the control group, Western blot was positive in 5.5%.

PMID- 17503224
TI  - A new approach to visualizing the membranous structures of the inner ear - high
      resolution X-ray micro-tomography.
AB  - CONCLUSION: Through the application of high resolution X-ray micro-tomography and
      a method of contrast enhancement based on en bloc staining in osmium tetroxide
      (OsO4), we report an approach that facilitates accurate three-dimensional (3D)
      reconstruction to reveal the fine structure of the inner ear. OBJECTIVES: To
      overcome the problems of artefacts, including tissue distortion and loss of 3D
      context that are inherent in existing methods that rely on manual dissection
      and/or histological sectioning. MATERIALS AND METHODS: A staining protocol was
      developed that involved the en bloc application of the OsO4 solution (2% w/v) for
      an extended period of time. The samples were then scanned using an X-ray micro
      tomography platform and subsequent 3D visualizations were constructed. RESULTS:
      The digital nature of the data allowed a complete 3D contextual visualization to
      be constructed whereby the individual sensory structures could be seen in
      relation to other inner ear structures. This included a detailed anatomy of the
      membranous labyrinth and nerve supply including the spatial configuration of the
      utricular and saccular maculae. This is a new way of undertaking temporal bone
      histology.

PMID- 17503225
TI  - Very far-advanced otosclerosis: stapedotomy or cochlear implantation.
AB  - CONCLUSION: Every patient with severe or profound hearing loss must have a
      temporal bone high-resolution computed tomography (CT) scan. Stapedotomy is a
      simple, safe and low-cost procedure compared with cochlear implantation and can
      provide very good results. This can justify our decision to propose stapedotomy
      at the initial treatment in patients with very far-advanced otosclerosis. In
      cases of hearing failure after stapes surgery, cochlear implantation is an
      option. OBJECTIVE: This study aimed to find the best first intention treatment of
      very far-advanced otosclerosis. MATERIALS AND METHODS: This was a retrospective
      study and included 14 patients with non-measurable preoperative bone and air
      conduction thresholds and otosclerosis on temporal bone high-resolution CT scan.
      Stapes surgery followed by a well fitted hearing aid was the initial treatment in
      11 patients and cochlear implantation in 7 patients, including 4 patients who had
      poor results after stapedotomy. Objective and subjective audiometric results were
      studied and compared between stapedotomy and cochlear implantation groups.
      RESULTS: Objective and subjective results were statistically better in the
      cochlear implant group than in the stapedotomy group. However, four patients in
      the stapedotomy group had comparable results to the patients with cochlear
      implants.

PMID- 17503226
TI  - Outcomes in adults implanted with the FLEXsoft electrode.
AB  - CONCLUSION: Achieving deep insertions, as well as good speech perception results,
      the FLEXsoft electrode array allows for some preservation in subjects with
      measurable low frequency hearing, even after a period of time. This opens the
      door for future research in electrode design, hearing preservation research and
      drug delivery systems. OBJECTIVES: The FLEXsoft electrode is designed to be
      atraumatic to the structures of the cochlea during deep insertion of a cochlear
      implant electrode. This paper reports on the surgical and functional outcomes in
      implantations with the FLEXsoft electrode array. PATIENTS AND METHODS: Twenty
      three adult subjects received a FLEXsoft electrode array and were assessed on
      speech perception tests (monosyllables, sentences in quiet and in noise), a
      subjective questionnaire (Nijmegen Cochlear Implant Questionnaire) and a pure
      tone audiogram. Results at 1, 3, 6 and 12 months post first fitting were compared
      to scores from the preoperative interval. RESULTS: Surgery was uneventful in all
      cases, the surgical handling was satisfactory and correct position of the
      electrode was achieved in all cases. Hearing could be preserved (as determined by
      the audiogram) in half of the subjects who had measurable audiograms
      preoperatively at the 1 month test interval, and in a quarter of subjects after
      12 months of device use, despite deep insertion of the electrode. Speech
      perception scores showed significant improvement over time, as did quality of
      life scores, and were comparable to results with the standard electrode array as
      used in the COMBI 40+ and PULSARCI100.

PMID- 17503227
TI  - Comparison of bacterial adherence to polylactides, silicone, and titanium.
AB  - CONCLUSIONS: Less bacterial adherence occurred on uncoated polylactide and
      silicone than on uncoated titanium surfaces. Albumin coating was an effective
      method to inhibit bacterial adherence to all these surfaces. As regards bacterial
      adherence, polylactides are at least as safe implant materials as silicone and
      titanium. OBJECTIVES: We compared adherence of Staphylococcus aureus and
      Pseudomonas aeruginosa to four implant materials and studied the inhibitory
      effect of albumin on adherence. The aims were to discover any differences between
      materials and to study the effectiveness of albumin coating. MATERIALS AND
      METHODS: Eight plates of polylactide A and B, silicone, and titanium were exposed
      to S. aureus and P. aeruginosa. Four of these plates were uncoated and four were
      coated with albumin. A total of 64 plates were included in the study. The
      bacteria were stained with acridine orange, and 10 photomicrographs of each plate
      allowed quantification of the surface area covered with bacteria. RESULTS: The
      most adherence occurred on titanium without coating. Albumin coating of the
      surface significantly reduced bacterial adherence to each material. Differences
      between materials with albumin coating were relatively small. Of the bacteria, P.
      aeruginosa had the greater capacity to adhere to a surface.

PMID- 17503228
TI  - The effects of different auditory activity on the expression of phosphorylated c
      Jun in the auditory system.
AB  - CONCLUSION: The data revealed that calcium influx via the NMDA receptor up
      regulated the expression of phosphorylated c-Jun in the primary auditory cortices
      following sensory stimulation and after different neural injury stimulations
      which guide activity-dependent changes in gene expression and neural plasticity.
      OBJECTIVES: Activator protein-1 (AP-1) transcription factor, which is mainly
      composed of c-Fos and c-Jun proteins, is believed to be a key participant in
      molecular processes that guide activity-dependent changes in gene expression. Our
      previous study had shown that the expression of NMDAR2A gene on synaptosomes
      membrane of auditory cortical neurons varied by electrical intracochlear
      stimulation (EIS) and neural injury induced by acoustic trauma. In this study, we
      investigated the role of the NMDA receptor (NMDAR) in regulating the expression
      of phosphorylated c-Jun in the primary auditory cortex (AI). The modulation
      factors observed for gene expression included EIS and noise traumas. MATERIALS
      AND METHODS: EIS was applied in rats with early postnatal auditory deprivation.
      The impact of the noise traumas on the ultrastructures of spiral ganglion neurons
      (SGNs) and their innervations to inner hair cells (IHCs) were verified by
      transmission electron microscopy (EM). These changes include a decrease in
      subcellular organelles, the swelling of mitochondria and endoplasmic reticulum,
      the morphological changes in cell nuclei, and damage in the afferent synapse.
      RESULTS: Immunohistochemistry observations showed that the expression of
      phosphorylated c-jun and active caspase-3 in hair cells and SGNs varied with
      amount of noise. Immunocytochemistry and Western blotting showed that the
      auditory cortex began to express phosphorylated c-jun 24 h after 2 h of EIS.
      However, this expression was not changed by EIS if NMDAR antagonist was applied.
      The level of phosphorylated c-Jun was remarkably increased in AI after noise
      overstimulation at 115 dB SPL for 3 h. Again, such an increase was not seen if
      NMDAR antagonist 3-(2 carboxypiperazin-4yl) propyl-1-phosphonic acid (CPP, 10
      mg/kg, i.p.) was applied 30 min before the noise exposure.

PMID- 17503229
TI  - Intratympanic gentamicin therapy for intractable Meniere's disease.
AB  - CONCLUSIONS: Intratympanic gentamicin treatment using a low dose of gentamicin
      (approximately 21-24 mg per injection) applied at intervals of a minimum of 27
      days, has been shown to be a successful treatment of vertigo. OBJECTIVES: The
      objective of this analysis was to evaluate the efficacy and side effects of
      intratympanic injections of gentamicin as treatment of intractable unilateral
      Meniere's disease. PATIENTS AND METHODS: This was a retrospective study in which
      57 patients treated with intratympanic gentamicin for Meniere's disease were
      analysed. Patients received between 1 and 10 intratympanic injections of
      gentamicin in an outpatient setting. RESULTS: Six months after treatment, overall
      complete or substantial vertigo control was reported by 80.7% of our patients
      (VCC class A, 61.4%; class B, 19.3%). Unilateral caloric weakness increased from
      50.1% to 79.8% after treatment, and complete caloric areflexia (30 degrees C and
      44 degrees C) was induced in 38.6%. In this study hearing worsened (> 10 dB =
      SNHL) in only 15.8% of our patients (range 10-29 dB) and loss of word recognition
      (WR) scores worsened (>15%) in 31% of the patients. Only 1 injection was
      necessary in 49.1% of the patients, the remaining 50.9% needed 2, 3, 4, 6 or 10
      injections, always with a time interval of a minimum of 27 days.

PMID- 17503230
TI  - Sulphurous-arsenical-ferruginous (thermal) water inhalations reduce nasal
      respiratory resistance and improve mucociliary clearance in patients with chronic
      sinonasal disease: preliminary outcomes.
AB  - CONCLUSIONS: In order to confirm these preliminary results, a prospective double
      blind study has been instituted in Padova University ENT Section to compare the
      efficacy of sulphurous-arsenical-ferruginous thermal water nasal irrigations vs
      isotonic sodium chloride solution nasal irrigations after functional endoscopic
      sinus surgery for chronic sinusitis. OBJECTIVES: Despite their widespread use,
      much uncertainty exists about the indications and therapeutic mechanisms of nasal
      thermal water inhalations in the treatment of sinonasal chronic disease. The aim
      of the present study was to evaluate the effects of sulphurous-arsenical
      ferruginous thermal water inhalations on nasal respiratory flow, mucociliary
      transport, nasal cytology, and chemo-physics of nasal mucus in a group of
      consecutive patients with chronic sinonasal disease. PATIENTS AND METHODS: Thirty
      seven patients with chronic sinonasal disease underwent a 12-day course of
      sulphurous-arsenical-ferruginous thermal water warm vapour inhalations (38
      degrees C) followed by nasal aerosol of the same thermal water (7 microns
      micelle). RESULTS: This preliminary study showed that a course of sulphurous
      arsenical-ferruginous thermal water inhalations determined a significant
      improvement in nasal flow and reduction of nasal resistance; a statistically
      significant reduction of mean mucociliary transport time, from pathologic to
      physiologic values, has also been shown. Statistical analysis of our data
      confirmed that the presence of nasal bacteria was significantly reduced by
      thermal water inhalations.

PMID- 17503231
TI  - The anterior ethmoidal artery: radio-anatomical comparison and its application in
      endonasal surgery.
AB  - CONCLUSION: High-resolution CT scans are able to determine with accuracy the
      location of the anterior ethmoidal artery in relation to the roof of the ethmoid.
      This investigation should greatly help functional endoscopic sinus surgery to
      avoid accidental injury of the artery and to coagulate the vessel in cases of
      severe epistaxis. OBJECTIVES: This was a radio-anatomical study of the anterior
      ethmoid artery in order to assess the course of the artery prior to endoscopic
      cauterization. MATERIALS AND METHODS: Eighteen ethmoid sinuses (nine heads) were
      dissected and high-resolution CT scans were performed in axial, coronal and
      sagittal planes. RESULTS: All anterior ethmoidal arteries were identifiable. The
      arteries were included in the roof of the ethmoid in eight cases. In three cases
      the arteries were prominent under the roof. In seven cases the dissection found
      the arteries distant from the roof. This anatomical feature was associated with
      pneumatization of the floor of the orbit. The correlation between CT scan and
      dissection was very satisfactory.

PMID- 17503232
TI  - Physical findings in the upper airways related to obstructive sleep apnea in men
      and women.
AB  - CONCLUSIONS, There are gender differences when it comes to the risk factors for
      sleep apnea. Large tonsils, a high tongue and a wide uvula are risk factors for
      sleep apnea in men, while large tonsils and a retrognathic mandible are risk
      factors in women. Upper airway abnormalities including mandibular retrognathia
      are, however, unable to predict sleep apnea among snorers being investigated for
      suspected sleep apnea. OBJECTIVES: To identify gender-specific risk factors for
      obstructive sleep apnea and the diagnostic performance from physical upper airway
      examinations among snoring men and women investigated because of suspected sleep
      apnea. PATIENTS AND METHODS: The dimensions of the uvula, tonsils, velopharynx
      and tongue, and nasal septal deviation, mandibular position, neck circumference,
      weight, and height were systematically scored in 801 consecutive snoring patients
      (596 men and 205 women), who had been referred for a primary sleep apnea
      recording. RESULTS: In men, large tonsils, a high tongue, and a wide uvula were
      independent factors associated with an apnea-hypopnea index of >15. In women,
      large tonsils and mandibular retrognathia were independent factors associated
      with an apnea-hypopnea index of >15. The positive predictive values for upper
      airway abnormalities ranged between 0.20 and 0.25 in men and between 0.09 and
      0.15 in women.

PMID- 17503233
TI  - SIS with tissue-cultured allogenic cartilages patch tracheoplasty in a rabbit
      model for tracheal defect.
AB  - CONCLUSIONS: In the rabbit model, small intestinal submucosa (SIS) compounded
      with tissue-cultured allogenic cartilages appeared to be an efficacious method
      for the patch repair of partial circumferential tracheal defects instead of
      autologous grafts. SIS appears to be a safe and promising means of facilitating
      neovascularization and tissue regeneration. The long-term use of SIS and tissue
      cultured allogenic cartilages warrants further investigation. BACKGROUND:
      Tracheal defect reparation remains a challenging surgical problem that can
      require reconstruction using autologous grafts or artificial stents. This study
      was performed to evaluate the efficacy of SIS, a biocompatible, acellular matrix,
      compounded with different tissue-cultured allogenic cartilages, in the repair of
      a critical-size tracheal defect. MATERIALS AND METHODS: A full-thickness defect
      (4 x 8 mm) was created in tracheal rings four to six in adult rabbits. A piece of
      8-ply SIS sandwiched in thyroid cartilage, auricular cartilage, or without
      cartilage, respectively (designated experiment 1, 2, or 3, respectively), was
      sutured to the edges of the defect with interrupted 4-0 polypropylene sutures. In
      control animals, the defect was closed with lamina praetrachealis. All animals
      were followed until signs of dyspnea became apparent or for 4 or 12 weeks. After
      follow-up and euthanasia, the trachea was harvested and prepared for histologic
      evaluation using conventional techniques. RESULTS: All animals tolerated the
      procedure well but two animals in group 1 (n=5), three in group 2 (n=5), and one
      in group 3 (n=5) had stridor after operation and expired within <1 month with
      different degrees of obstruction. The other animals in these groups and the
      control animals (n =3) all survived >1 month. Histologically, neovascularization
      of the patch was noted with moderate inflammation. The surface of the SIS patch
      was covered with a lining of ciliated epithelial cells. The tissue-cultured
      allogenic cartilages degraded to some extent.

PMID- 17503234
TI  - Voice function following CO2 laser microsurgery for precancerous and early-stage
      glottic carcinoma.
AB  - CONCLUSIONS: With the cover layer injured, vocal function of mucosal ablation
      could be protected and even return to normal after surgery and vocal function of
      mucosal stripping was slightly affected with extensive mucosal injury. Once the
      body layer was injured, the compensatory mechanism would play an important role
      in phonation. OBJECTIVES: To investigate voice function following CO2 laser
      microsurgery for precancerous and early-stage glottic carcinoma. PATIENTS AND
      METHODS: Vocal function was examined by acoustic analysis, aerodynamic analysis
      and videostroboscopic examination. RESULTS: For mucosal ablation, vocal quality
      recovered 1 month after surgery. For mucosal stripping, although vocal quality
      was steady 3 months after surgery, slight hoarseness persisted in this group. The
      contour of the treated fold recovered postoperatively. There were no
      complications in recovery. For cordectomies, vocal quality became steady 6 months
      after the surgery. The supraglottal hyperfunction with supraglottal structure
      squeezing played an important role in phonation. The affected vocal fold mucosal
      wave was absent instead of a regular ventricular fold wave or mucosal wave of the
      vocal process during phonation. In comparison with the type III-IV cordectomy,
      the results of extended cordectomies (type Va and Vc) were worse; however, the
      difference was not statistically significant. Granulomas and anterior commissure
      webs were present. All granulomas resolved spontaneously 3 months
      postoperatively.

PMID- 17503235
TI  - Extended supracricoid laryngectomy with excision of both arytenoids: the modified
      reconstructive laryngectomy.
AB  - CONCLUSION: Modified reconstructive laryngectomy (MRL) with excision of both
      arytenoid cartilages will expand the range of indications for conservative
      surgery in the management of cancer of the larynx. OBJECTIVE: The present work
      describes a modification of the standard reconstructive laryngectomy procedure,
      in order to address problems related to aspiration, and to improve functional
      results. PATIENTS AND METHODS: The study was conducted in Cairo University
      Hospital. MRL was performed on 14 patients who were scheduled for total
      laryngectomy. This technique allows for preservation of the superior laryngeal
      nerves, by fashioning folds of the pharyngeal mucosa to replace the arytenoids.
      This is followed by reconstruction of the airway through elevation and attachment
      of the remaining tracheal rings and/or cricoid to the hyoid bone and epiglottis.
      RESULTS: MRL was successful in all of the 14 patients included in this
      preliminary study. All of the patients maintained comprehensible speech, and only
      one required a speaking type of tracheotomy tube.

PMID- 17503236
TI  - Survival study and treatment strategy for second primary malignancies in patients
      with head and neck squamous cell carcinoma and nasopharyngeal carcinoma.
AB  - CONCLUSION: Patients at risk of developing second primary malignancies (SPMs)
      comprise those with primary hypopharyngeal, laryngeal, and oral cavity index
      cancers, patients with well-differentiated squamous cell carcinomas, those aged
      >70 years, patients who are heavy smokers, alcohol drinkers, or betel quid
      chewers, and those with a family history of SPM. OBJECTIVE: SPMs are commonly
      found after successful treatment of index cancers in the head and neck region;
      however, treatment guidelines for SPMs have not been established. We compared the
      differences in the clinical characteristics, treatment outcomes, and 10-year
      survival rate between patients with SPMs who had been treated for head and neck
      squamous cell carcinoma (HNSCC) and those who had been treated for nasopharyngeal
      carcinoma (NPC) in order to establish an effective treatment strategy. PATIENTS
      AND METHODS: This was a 10-year retrospective study of 125 patients who had
      developed SPMs after being treated for either HNSCC or NPC during the period from
      January 1995 to July 2005. The average follow-up time was 34.9 months, and the
      setting for the study was a tertiary referral center. RESULTS: The survival rate
      of patients with SPMs is not significantly poor. The survival is worse if the SPM
      is associated with a primary advanced stage index cancer or it is synchronous; if
      the SPM occurs in an area other than the head and neck region; or if SPM patients
      undergo palliative treatment.

PMID- 17503237
TI  - Normative values for the assessment of gustatory function using liquid tastants.
AB  - CONCLUSION: The present study introduces normative data for the 'three-drop test'
      of gustatory function. OBJECTIVES: Although in some instances liquid tastants
      appear to be preferable for the measurement of taste function, no such test has
      been established for the routine clinical testing. The aim of the present study
      was to provide normative data for a test system based on administration of taste
      solutions. SUBJECTS AND METHODS: The investigation involved 230 participants (104
      female, 126 male, mean age 39 years, age range 14-79 years). After establishing
      the concentration range of the taste solutions, recognition thresholds were
      obtained for the four basic tastes using a three-alternative forced choice
      paradigm (three-drop test). RESULTS: The study confirmed previous observations on
      effects of age and sex on gustatory function, with younger subjects being more
      sensitive than older ones, and women being more sensitive than men.

PMID- 17503238
TI  - Subglottic and tracheal stenosis associated with multifocal fibrosclerosis.
AB  - This is the first case report in the literature of idiopathic subglottic and
      tracheal stenosis in a patient diagnosed with multifocal fibrosclerosis (MFS).
      The patient had unilateral orbital pseudotumour, bilateral pretibal cutaneous
      manifestations and raised thyroid antibodies, which might indicate subclinical
      thyroid involvement. Urgent permanent tracheostomy was needed. The patient also
      underwent tracheal dilatation for her dysphonia. There was no evidence of brain,
      lung, liver or renal involvement. Although extremely rare, laryngologists should
      consider the possibility of such a diagnosis in a stridulous patient with
      multifocal fibrotic manifestations.

PMID- 17503239
TI  - A rare case of jugular foramen schwannoma arising from Jacobson's nerve.
AB  - The jugular foramen (JF) region is a complex area of the cranial base where
      venous structures such as the jugular bulb and the inferior petrosal sinuses are
      strictly related to the lower cranial nerves IX, X and XI. The most common
      tumours include glomus jugulare, schwannomas of the mixed cranial nerves (IX-XI)
      and meningiomas. Schwannomas involving the jugular foramen are rare neoplasms and
      in most of the cases are thought to originate from the X cranial nerve. We report
      a case of a schwannoma of the JF diagnosed at an early stage, allowing
      radiological and surgical evidence to support its origin from the tympanic branch
      of the IX cranial nerve. To our knowledge this is the first case reported in the
      literature of such a tumour.

PMID- 17503240
TI  - Dimethylacetamide-induced hepatic injuries among spandex fibre workers.
AB  - OBJECTIVES: To investigate clinical features of dimethylacetamide-induced hepatic
      injuries (DIHIs). METHODS: Workers exposed to dimethylacetamide (DMAc) in two
      spandex factories were monitored for DIHI. We identified 38 DIHI cases as study
      subjects between 2001 and 2004. DMAc exposure was estimated with urinary N
      methylacetamide (NMAc) results from 2003 to 2004. RESULTS: All 38 cases showed
      hepatocellular-type liver injury. The interval between first exposure and
      identification of hepatic injury (latent period) was mostly less than two months
      and never exceeded six months. In addition, three repeat DIHI cases showed much
      shorter latent periods for recurrence than their initial latent periods of
      hepatic injury. A 50% decline of serum alanine aminotransferase (ALT) levels
      after the cessation of DMAc exposure took less than 14 days and a 90% decline
      less than 31 days. The median urinary NMAc level of DIHI group (samples from the
      department of DIHI cases) was 25.1 mg/g Cr; higher than that of all other urinary
      NMAc results (11.8 mg/g Cr). CONCLUSIONS: Our data suggest that DMAc can induce
      hepatocellular-type liver injury and the mechanism of DIHI may be idiosyncratic.
      Although our exposure estimation was incomplete, the workers with DIHIs might be
      exposed to higher levels of environmental DMAc than the workers who did not
      develop DIHIs. All workers exposed to DMAc need to be closely observed for
      occurrence of hepatic injury for at least six months.

PMID- 17503241
TI  - Explaining differences in operating costs among poison control centers: an
      exploratory study.
AB  - OBJECTIVES: To explore the effects of population, staffing, location, and funding
      on cost per human poison exposure call; and organizational characteristics
      differentiating higher- and lower-cost centers. METHODS: Data from 65 poison
      control centers (2001) were analyzed with linear multiple regression; qualitative
      data from 10 centers were compared. RESULTS: The most important predictor of
      expenses per call was 24-hour coverage by Specialists in Poison Information
      ($15.70 of $40.53/call). Other factors increasing total expenses included
      northeast location and more health educator FTEs. Qualitative information
      revealed that more complex organizational forms, including multiple reporting and
      accountability relationships, characterized higher-cost centers. Surprisingly,
      having a wider range of reported activities (less specialization) was more common
      among lower-cost centers. CONCLUSIONS: Wide variability in cost per call suggests
      that inefficiencies exist. While elimination of inefficient poison control
      centers could reduce costs, the loss of training and collaborative opportunities,
      and preparedness for public health emergencies and bio-terrorism events, might
      mitigate against such restructuring.

PMID- 17503242
TI  - Accidental exposure to oral rabies vaccine.
AB  - BACKGROUND: To combat raccoon rabies, various government agencies have
      implemented a plan to distribute oral rabies vaccine (ORV) in wooded areas. The
      bait blocks containing ORV are available for its intended population but also for
      humans and domestic animals. METHODS: A regional poison information center (RPIC)
      identified all exposures to ORV from 2002-2004 reported to the center. RESULTS:
      Twenty-two accidental exposures to the ORV were reported. Eight (36%) of the
      exposures were human and 14 (64%) were domestic animals. The animal exposures
      were oral while the human contaminations were oral (1), dermal (6), inhalation
      (1), and ocular (1). Eight of the cases involved multiple victims. No symptoms
      were reported in the humans or canines although the feline died (unsubstantiated
      if related). Treatment consisted of irrigation/dilution and in one instance
      emesis was induced. CONCLUSION: In this case series, accidental exposure to ORV
      posed no hazard to domestic animals or humans.

PMID- 17503243
TI  - Oral C-4 plastic explosive in humans - a case series.
AB  - INTRODUCTION: C-4 is a plastic explosive widely used for demolition in both
      military and civilian settings. Severe toxicity following unintentional oral
      exposures or abuse have been reported in single case reports and small case
      series. CASE SERIES: Seventeen previously healthy male Army commandos admitted to
      a secondary referral hospital in Sri Lanka following oral C-4 poisoning. METHODS:
      This data was collected as part of a prospective cohort study recruiting all
      patients admitted to general hospitals in Sri Lanka with a history of poisoning.
      History, clinical, and laboratory outcomes were recorded until discharge.
      RESULTS: All 17 patients survived. The prominent clinical features were seizures,
      headache, nausea, and vomiting. Hypokalaemia and elevation of creatine kinase,
      lactate dehydrogenase, and phosphate were noted in all but two patients.
      Metabolic acidosis occurred in two patients following seizures and this resolved
      spontaneously. CONCLUSIONS: Management recommendations include standard
      resuscitation, supportive care, and benzodiazepines for the control of seizures
      or agitation. Poisoning with C-4 is an unusual cause of seizures which should be
      considered in patients with access to this agent.

PMID- 17503244
TI  - Urinary serotonin level is associated with serotonin syndrome after moclobemide,
      sertraline, and citalopram overdose.
AB  - INTRODUCTION: Altered mental status, autonomic dysfunction, and neuromuscular
      abnormalities are a characteristic triad of serotonin syndrome. No laboratory
      tests confirm the diagnosis of serotonin syndrome. CASE REPORT: A 35-year-old
      woman took moclobemide, sertraline, and citalopram in a suicide attempt. She was
      conscious with mild tachycardia, hypertension, and tachypnea one hour after
      ingestion. In the second hour after ingestion diaphoresis, mydriasis, horizontal
      nystagmus, trismus, hyperreflexia, clonus, and tremor appeared. She became
      agitated and unresponsive. In the third hour after ingestion she became comatose
      and hyperthermic. She was anesthetized, paralyzed, intubated, and ventilated for
      24 hours. Serum moclobemide, sertraline, and citalopram levels were above
      therapeutic levels. The serum serotonin level was within normal limits and the
      urinary 5-hydroxyindoleacetic acid:creatinine ratio was below the average daily
      value. The urinary serotonin:creatinine ratio was increased on arrival (1 mg/g).
      DISCUSSION AND CONCLUSION: The urinary serotonin level is increased in serotonin
      syndrome due to a monoamine oxidase inhibitor and selective serotonin-reuptake
      inhibitors overdose. It is possible that urinary serotonin concentration could be
      used as a biochemical marker of serotonin syndrome.

PMID- 17503245
TI  - Cytochrome-C oxidase inhibition in 26 aluminum phosphide poisoned patients.

PMID- 17503247
TI  - Plasma surfactant D in patients following acute paraquat intoxication.
AB  - Free radical-induced lung injury is a major problem that occurs because of
      paraquat intoxication. Serum surfactant protein D (SP-D) reflects the severity of
      various lung diseases. The purpose of this study is to investigate the changes in
      plasma SP-D concentrations and to correlate disease severity with SP-D
      concentrations in patients with acute paraqaut intoxication. Twelve paraquat
      intoxicated patients participated in this study. Their paraquat exposure was
      assessed by their plasma's paraquat level. Serial plasma SP-Ds were measured by
      ELISA. SP-D was decreased two and three days after the initial measurement within
      2 to 72 hours of ingestion. There was no difference in initial SP-D levels
      between survivors and non-survivors. The SP-D test revealed a significant
      positive correlation between the SP-D level and PaO(2) (r = 0.384, p = 0.003, N =
      57). SP-D did not predict the likelihood of survival, but it was positively
      correlated with PaO(2). This finding suggests that low concentrations of plasma
      SP-D could reflect hypoxia due to free radical-induced injury.

PMID- 17503248
TI  - Successful organ transplantation after treatment of fatal cyanide poisoning with
      hydroxocobalamin.
AB  - BACKGROUND: Cyanide-poisoned patients are potential organ donors provided that
      organs are not damaged by the poison or by antidotal treatment. CASE STUDY: A
      patient with third-degree burns and smoke inhalation-associated cyanide poisoning
      confirmed by measurements of whole blood cyanide was found in cardiac arrest and
      administered epinephrine and hydroxocobalamin (5 g + 5 g). Cardiac activity
      resumed, but the patient was declared brain dead on the third day of
      hospitalization when coma deteriorated to a shock state with refractory
      hypoxemia. Kidneys, heart, and liver were removed and transplanted into four
      patients. Gross pre-transplantation inspection of the donor organs and renal
      histology showed no evidence that hydroxocobalamin caused organ toxicity. Donor
      organs functioned normally through follow-up periods of several months.
      CONCLUSION: Anoxic cardiac arrest following acute cyanide poisoning treated with
      hydroxocobalamin (5 g + 5 g) was not a contraindication to organ transplantation
      after confirmed encephalic death in this patient.

PMID- 17503249
TI  - Rattlesnake envenomation with neurotoxicity refractory to treatment with
      crotaline Fab antivenom.
AB  - INTRODUCTION: Neurotoxicity following rattlesnake envenomation is reported with
      certain crotaline species. In some instances, crotaline Fab antivenom therapy
      that effectively halts progression of local tissue edema and hemotoxicity fails
      to reverse neurologic venom effects. CASE SERIES: A 50-year-old man presented
      following a rattlesnake envenomation to the left ring finger. He had swelling and
      pain in the affected hand and complained of dyspnea and dysphonia. Significant
      fasciculations were seen in the face, tongue, neck, trunk, and arms. The patient
      received crotaline Fab antivenom but continued to develop worsening respiratory
      distress. His respiratory insufficiency requiring ventilatory support appeared
      related to respiratory muscle incoordination as extremity motor function remained
      intact. Initial control of local edema progression and hematologic parameters was
      achieved with antivenom, but diffuse fasciculations involving the entire body
      worsened despite aggressive antivenom treatment. In another case, a 9-year-old
      boy was envenomated by a rattlesnake on the left thenar eminence. He presented
      with pain and swelling up to the forearm and fasciculations of the tongue, face,
      and upper extremities. The progression of edema was halted at the mid-bicep level
      and hematologic parameters normalized with crotaline Fab antivenom. However,
      fasciculations continued for two days despite antivenom treatment. CONCLUSION: We
      describe two cases of neurotoxicity following rattlesnake envenomation in which
      treatment with crotaline Fab antivenom adequately obtained initial control of
      local swelling and hematologic effects, but neurotoxic venom effects remained
      refractory to antivenom therapy. This phenomenon is anecdotally recognized
      following certain crotaline species envenomations.

PMID- 17503250
TI  - 24-hour provoked urine excretion test for heavy metals in children with autism
      and typically developing controls, a pilot study.
AB  - INTRODUCTION: The complementary and alternative medicine practice of prescribing
      chelators to children with autism is based on the premise that the chronic
      symptoms of autism can be ameliorated by reducing heavy metal body burden.
      However, there has not been definitive evidence, published to date, to support
      the assertion that children with autism are at increased risk of an excess
      chelatable body burden of heavy metals. The oral chelator meso-2,3
      dimercaptosuccinic acid (DMSA) can be used diagnostically to mobilize heavy
      metals from extravascular pools, enhancing the identification of individuals who
      have a chelatable body burden. METHODS: Seventeen children with autism and five
      typically developing children were enrolled in a pilot study to test for
      chelatable body burden of Arsenic (As), Cadmium (Cd), Lead (Pb), and Mercury
      (Hg). Evaluation included a questionnaire regarding potential exposure to heavy
      metals, diet restrictions, a baseline 24-hour urine collection, and a DMSA
      provoked urine collection. Urine collections were sent for As, Cd, Pb, and Hg
      quantification by Inductively Coupled Plasma-Mass Spectrometry. Unprovoked
      reference ranges were used in the interpretation of all collections. RESULTS:
      Fifteen autistic children and four typically developing children completed the
      study. Three autistic subjects excreted one metal in greater quantity during the
      provoked excretion than baseline. Two of these were very close to the limit of
      detection. In the third case, the provoked excretion of mercury was between the
      upper limit of normal and lower limit of the potentially toxic reference range.
      Fish was removed from this child's diet for greater than one month, and the
      provoked excretion test repeated. The repeat excretion of mercury was within the
      normal range. CONCLUSION: In the absence a proven novel mode of heavy metal
      toxicity, the proportion of autistic participants in this study whose DMSA
      provoked excretion results demonstrate an excess chelatable body burden of As,
      Cd, Pb, or Hg is zero. The confidence interval for this proportion is 0-22%.

PMID- 17503251
TI  - Supratherapeutic doses of sulfonylureas in diabetic patients: how much is too
      much?
AB  - BACKGROUND: Determining triage guidelines for supratherapeutic ingestions of
      sulfonylureas is difficult because they have broad therapeutic indexes. This
      study was performed to evaluate the degree of hypoglycemia that may result from a
      supratherapeutic ingestion of a sulfonylurea in a diabetic patient. METHODS:
      Poison center records over a 3-year period were retrospectively reviewed for
      cases of adults acutely ingesting supratherapeutic doses of sulfonylureas (SFU).
      RESULTS: A total of 85 cases were identified. Eight patients had complaints of
      shakiness or dizziness, but no patient developed symptoms refractory to oral
      glucose/carbohydrate supplementation or required intravenous dextrose.
      CONCLUSIONS: In our study, all diabetic patients accidentally ingesting more than
      their usual single dose (USD) or usual daily dose (UDD) of their SFU were safely
      monitored at home while observing for subjective or objective signs of
      hypoglycemia. When necessary, oral dextrose could be administered in these
      patients at home.

PMID- 17503252
TI  - Toxicology of the newer neonicotinoid insecticides: imidacloprid poisoning in a
      human.
AB  - Imidacloprid, a potent neonicotinoid insecticide, is currently one of the best
      selling insecticides. We report a patient with clinical toxicity due to the
      ingestion of imidacloprid in a deliberate suicide attempt. The structure and mode
      of action of imidacloprid are discussed.

PMID- 17503253
TI  - Brodifacoum poisoning with toxicokinetic data.
AB  - The case of a 46-year-old woman who survived after a brodifacoum poisoning is
      presented. The patient was admitted due to a severe coagulopathy. Initial
      prothrombin time and activated partial thromboplastin time were both greater than
      110 seconds and the patient suffered severe gastric and pulmonary hemorrhage
      requiring fresh frozen plasma transfusion and parenteral phytonadione
      administration (up to 100 mg per day). Serum brodifacoum levels were determined
      by HPLC during seven months. Five days after admission, serum brodifacoum level
      was 1302 ng/ml. Serum brodifacoum levels decreased till day 209 when became not
      detectable. Brodifacoum elimination showed a first order kinetic and a 56-day
      half-life. Investigation of superwarfarin should be considered in any patient
      with vitamin K dependent coagulation disorder. It would be also useful to obtain
      periodic brodifacoum levels and build the corresponding elimination curve to help
      direct phytonadione therapy in poisoned patients.

PMID- 17503254
TI  - Environmental Arsenic Exposure and Urinary 8-OHdG in Arizona and Sonora.
AB  - Although at high levels arsenic exposure is associated with increased cancer
      incidence, information on the health effects of lower exposure levels is limited.
      The objective of this study was to determine whether arsenic at concentrations
      below 40 microg/L in drinking water is associated with increased urinary 8
      hydroxydeoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage and repair.
      Urine samples were collected from 73 nonsmoking adults residing in two
      communities in Arizona (mean tap water arsenic (microg/L) 4.0 +/- 2.3 and 20.3 +/
      3.7), and 51 subjects in four communities in Sonora, Mexico (mean tap water
      arsenic (microg/L) ranging from 4.8 +/- 0.1 to 33.3 +/- 0.6). Although urinary
      arsenic concentration increased with higher exposure in tap water, urinary 8-OHdG
      concentration did not differ by community within Arizona or Sonora, and was not
      associated with urinary arsenic concentration. At the exposure levels evaluated
      in this study, drinking water arsenic was not associated with increased DNA
      oxidation as measured by urinary 8-OHdG.

PMID- 17503255
TI  - Development and implementation of an emergency department observation unit
      protocol for deliberate drug ingestion in adults - preliminary results.
AB  - BACKGROUND: Patients presenting after reported overdose are typically precluded
      from admission to emergency department observation units (EDOU). The purpose of
      this study was to describe the initial experience with an EDOU overdose protocol.
      METHODS: Retrospective chart review of all individuals presenting to a tertiary
      care hospital with a chief complaint of overdose or intoxication for the period
      7/1/2004 through 12/24/2004. Inclusion criteria for EDOU placement included
      asymptomatic patients aged >or= 15 years presenting after known or suspected
      potentially toxic exposure. Exclusion criteria included isolated ethanol
      intoxication, presence of persistent self-injurious or violent behaviors, chronic
      intoxication, ingestion of sustained release preparation, and presence of
      previously defined high-risk criteria. RESULTS: Retrospective chart review
      demonstrated that 163 patients presented to the ED after ingestion during this
      time period, of which 15 were excluded secondary to age. Six patients were
      admitted to the EDOU. No patient eloped or attempted further self-harm while in
      the EDOU. No clinical decompensation occurred. Another 27 patients were
      retrospectively identified as EDOU candidates, eight of whom were admitted to the
      MICU. CONCLUSION: Although initial numbers are too small for meaningful analysis,
      the results suggest that prolonged observation of this problematic patient subset
      within an EDOU is feasible.

PMID- 17503256
TI  - An immunochromatographic test for the diagnosis of ricin inhalational poisoning.
AB  - INTRODUCTION: Aerosolized ricin is a feared bioweapon for which no diagnostic
      protocol is currently available. METHODS: We obtained antibodies to develop an
      immunochromatographic test (ICT) that would be part of such a protocol. RESULTS:
      Our ICT, that can be read with the naked eye, has a sensitivity of 1 ng ricin/mL
      buffer, without enhancement, making it the most sensitive rapid test available
      for this toxin as far as we know. Its dynamic range extends to 10 microg/mL, with
      a plateau from 10 to at least 250 microg/mL (no "hook effect"), and it has
      limited cross-reactivity with other lectins. DISCUSSION: Calculated from
      experimental and animal data, sampling with nasal swabs and testing with the
      devised ICT should give more than a thousand times the sensitivity required to
      diagnose ricin inhalational poisoning. Such a margin is particularly valuable in
      the absence of clinical data. CONCLUSION: This cost-effective and easy to use
      diagnostic tool could assist in the diagnosis of inhalational exposure from ricin
      aerosols.

PMID- 17503257
TI  - Potency of five structurally different acetylcholinesterase reactivators to
      reactivate human brain cholinesterases inhibited by cyclosarin.
AB  - Acetylcholinesterase (AChE; EC 3.1.1.7) reactivators are used as a part of the
      antidotal therapy of organophosphorus pesticide and nerve agent intoxications.
      Cyclosarin is one member of the nerve agent family. In this article, we compared
      the reactivation potency of five structurally different AChE reactivators
      (pralidoxime, trimedoxime, methoxime, HS-6, and BI-6) to reactivate cyclosarin
      inhibited cholinesterases of human brain. The results demonstrate that the
      bisquaternary monooxime reactivator BI-6 seems to be the most potent reactivator
      of cyclosarin-inhibited cholinesterases. Moreover, according to the results, we
      can describe basic structural requirements, which are necessary for the
      efficacious reactivation process.

PMID- 17503258
TI  - Extremely slow formate elimination in severe methanol poisoning: a fatal case
      report.
AB  - Methanol poisoning is a potentially fatal medical emergency because of its
      metabolism to formic acid. The half-life of formate has been reported in the
      range of 2.5-12.5 hours, but the degree of inter-individual variation is not
      known. We studied methanol and formate kinetics in a case of late diagnosed
      methanol poisoning with persisting metabolic acidosis and circulatory failure.
      CASE REPORT: A 63-year-old man was referred to our hospital with a tentative
      diagnosis of stroke. He was awake on admission, but he soon deteriorated in the
      emergency department and a metabolic acidosis was revealed. Methanol poisoning
      was then suspected approximately five hours after admission but in spite of
      intensive treatment he died after six days. RESULTS: The S-methanol half-lives
      during treatment with fomepizole before and during hemodialysis were 49.5 and 4.1
      hours, respectively, while the similar half-lives of S-formate were 77.0 and 2.9
      hours. S-fomepizole was measured and found to be within the therapeutic range
      during treatment. DISCUSSION: The patient was treated with the established dosing
      regimen for fomepizole and the measured S-fomepizole levels throughout the
      treatment were adequate; the S-methanol elimination also suggests that methanol
      metabolism was blocked. Hence, other explanations for this exceptionally long
      formate half-life include slow formate metabolism, due to small hepatic folate
      stores or to genetic deficiencies in formate-metabolizing enzymes, or slow
      formate excretion, due to renal tubular acidosis, to a non-oliguric renal
      failure, or to genetic deficiencies in the renal formate transporters.
      CONCLUSION: This case report indicates that the half-life of S-formate may have
      greater inter-individual variation than earlier expected, being by far the
      longest half-life reported in the medical literature. These results support the
      use of hemodialysis in the treatment of such patients.

PMID- 17503259
TI  - Consumer perception of household hazardous materials.
AB  - We evaluated consumer perception of household hazardous materials (HHM) to
      identify links between storage of HHMs and consumer perception. METHODS: 357
      telephone surveys were conducted within one county to determine home storage
      location (high, low, unknown) of 10 substances common to pediatric poisoning.
      Questions addressed look-alikes, poison information resources, disposal/recycling
      practices, and the transfer of cleaning products to other containers. RESULTS:
      Prescription medications were stored in lower elevations than vitamins with iron
      and OTC ibuprofen or acetaminophen. Products common in poisoning were often
      stored at low elevations. Poison center (PCC) awareness was modest; 35% stated
      the PCC would be first choice; 43% chose 911. Nineteen percent indicated they
      transferred cleaning items to other containers, usually bleach (6.7%), but 29%
      transferred prescription medications. CONCLUSION: Results will be utilized to
      develop a community-specific educational campaign targeted toward lack of
      awareness of the poison center and reinforcement of proper storage and disposal
      practices.

PMID- 17503260
TI  - Reversal of salicylate-induced euglycemic delirium with dextrose.
AB  - Salicylate poisoning inhibits Krebs cycle enzymes and uncouples oxidative
      phosphorylation. Under these circumstances, we hypothesize that CNS glucose
      supply is sometimes unable to keep up with demand resulting in hypoglycorrhacia
      and delirium even in the face of serum euglycemia. Supporting this conjecture, we
      report two euglycemic patients with salicylate-induced delirium who responded to
      boluses of concentrated dextrose with a prompt improvement in mental status.

PMID- 17503261
TI  - Two cases of acute endosulfan toxicity.
AB  - BACKGROUND: Endosulfan is widely used in insect control and is absorbed by both
      humans and animals through the intestinal tract, the lungs, and the skin.
      Organochlorine insecticides are highly toxic compounds that are responsible for a
      number of severe intoxications worldwide, with several deaths. A 9-year analysis
      by one of Turkey's poison control centers reported that pesticide intoxications
      accounted for 8.8% of 25,572 poisoning calls, with 80.3% of them relating to
      insecticides and 19.7% concerning rodenticides. CASE REPORTS: We present two
      cases of unintentional exposure to endosulfan, one of which presented with
      neurological manifestations, liver toxicity, and required mechanical ventilation
      and emergent hemodialysis; the other had only neurological manifestations and
      liver toxicity. CONCLUSION: In cases of endosulfan poisoning, physicians must be
      aware of neurological manifestations, seizures, and severe metabolic acidosis. If
      severe metabolic acidosis is present, we suggest that hemodialysis may be an
      important intervention and should be performed early.

PMID- 17503262
TI  - Abrupt awakening phenomenon associated with gamma-hydroxybutyrate use: a case
      series.
AB  - Case reports mention a sudden awakening from GHB-associated coma but do not
      specify its time course. The aim of the present case series was to investigate
      the time course of the awakening from GHB intoxication and the relationship to
      plasma concentrations of GHB and the presence of other drugs. Unconscious (GCS
      <or=8) participants at six large rave parties who were treated at medical
      stations were included. Serial blood samples were taken every 10 to 30 minutes
      for toxicological analysis. At the same time-points, the depth of coma was scored
      with the Glasgow Coma Score (GCS). Fifteen out of 21 unconscious patients proved
      to be positive for GHB. Fourteen of these had ingested one or more other drugs.
      The median GHB plasma concentration upon arrival in the medical station was 212
      microg/ml (range 112 to 430 microg/ml). In 10 patients the GCS was scored more
      than twice, allowing study of the time course. The GCS of these patients remained
      <or=8 for a median time of 90 minutes (range 30 to 105 minutes). The duration of
      the transition between GCS of <or=8 and >or=12 was 30 minutes (range 10 to 50
      minutes). A subgroup of five patients had a GCS of 3 upon arrival and remained at
      3 for a median time of 60 minutes (range 30 to 110 minutes), while the median
      time for the transition between the last point with GCS 3 and the first with GCS
      15 was 30 minutes (range 20 to 60 minutes). This case series illustrates that
      patients with GHB intoxications remain in a deep coma for a relatively long
      period of time, after which they awaken over about 30 minutes. This awakening is
      accompanied by a small change in GHB concentrations. A confounding factor in
      these observations is co-ingested illicit drugs.

PMID- 17503263
TI  - Amatoxin poisoning: a 15-year retrospective analysis and follow-up evaluation of
      105 patients.
AB  - INTRODUCTION: Fatalities due to mushroom poisonings are increasing worldwide,
      with more than 90% of deaths resulting from ingestion of amatoxin-containing
      species. METHODS: A retrospective evaluation of the history and clinical outcome
      of each patient treated from 1988 to 2002 in the Toxicological Unit of Careggi
      General Hospital (University of Florence, Italy) for amatoxin poisoning. Data
      included the biological parameters monitored, the treatment protocols used
      (intensive fluid and supportive therapy, restitution of the altered coagulation
      factors, multiple-dose activated charcoal, mannitol, dexamethasone, glutathione,
      and penicillin G), and outpatient follow-up evaluations. RESULTS: The clinical
      data of 111 patients were evaluated; their biological parameters were monitored
      every 12-24 hours until discharge. Two patients died; both were admitted to the
      hospital more than 60 hours after mushroom ingestion. Of all the laboratory
      parameters evaluated, the evolution of hepatic transaminases and prothrombin
      activity over four days were the most predictive indicators of recovery or death.
      Our follow-up evaluation of 105 patients demonstrated that our survivors
      recovered completely. CONCLUSIONS: Our experience indicates that the protocol
      used in our Toxicologicy Unit is effective for amatoxin poisoning, and that all
      patients treated within 36 hours after mushroom ingestion were cured without
      sequelae.

PMID- 17503264
TI  - Alerting and Surveillance Using Poisons Information Systems (ASPIS): outcomes
      from an international working group.
AB  - BACKGROUND: In recent years, awareness of the risks of chemical and poison
      exposure has increased, and a number of highly publicized terrorist events have
      heightened community fears. In particular, there is concern surrounding the
      potential risk of a covert release, which underpins the need to develop robust
      methods of population surveillance. AIMS AND METHODS: This article outlines the
      proceedings of a working group and focuses on the need for greater international
      cooperation and understanding of existing toxicological surveillance systems in a
      variety of countries. Poison control centers have well-established local networks
      and experienced staff, which make them well-placed to detect chemical and poison
      release. This needs further development to ensure timely detection of signals,
      which might be better achieved by robust international networks and consistent
      use of data collection tools. We illustrate some of the strengths and weaknesses
      of existing surveillance methods, and present a position statement on the minimum
      dataset required by future surveillance systems. CONCLUSIONS: Poison control
      centers provide a useful platform for developing surveillance activity. Having
      proposed a number of common aims and objectives, it is hoped that these consensus
      statements will inform decision makers and stimulate discussion of how
      international toxicological surveillance programs might best be developed.

PMID- 17503266
TI  - Laboratory diagnosis of toluene-based inhalants abuse.
AB  - Toluene is the main substance contained in products used as inhalants. The
      frequent abuse of toluene-based inhalants requires the definition of a simple
      laboratory parameter that allows acute exposure assessment. This study aimed at
      defining urinary hippuric acid (UHA) levels related to intentional exposure to
      toluene, and to correlate them to blood toluene concentration (BT). METHODS: BT
      and UHA levels were measured in 65 homeless adolescents of Porto Alegre, Brazil.
      RESULTS: Toluene was detected in 91.9% of the investigated population, who
      presented BT levels from 0.5 to 83.7 microg/mL. There was good correlation
      between UHA and BT concentrations (r = 0.78), and in homeless adolescents, UHA
      levels higher than 3.0 g/g creatinine indicate intentional exposure to toluene.
      CONCLUSIONS: The determination of UHA concentrations can be used as a screening
      method for the detection of intentional exposure to toluene, but its diagnosis
      must include BT toluene dosage, as well as circumstantial and clinical evidence.

PMID- 17503265
TI  - Traditional kava beverage consumption and liver function tests in a predominantly
      Tongan population in Hawaii.
AB  - PURPOSE: To determine the effects of traditionally prepared kava beverages on the
      liver function tests of regular kava beverage consumers in a population of Tongan
      and non-Tongan residents of Hawaii (Oahu). METHODS: The liver function tests of
      31 healthy adult kava drinkers were compared against a control group of 31
      healthy adult non-kava drinkers. Subjects were recruited from the general
      population, a kava bar, and Tongan kava drinking circles. The liver function
      profile included AST, ALT, ALP, GGT, and bilirubin (total and direct). Other
      tests included total protein, albumin, and screens for viral hepatitis and
      hemochromatosis when indicated. RESULTS: Chronic kava beverage consumption was
      associated with elevation of GGT in 65% of the kava drinkers versus 26% in the
      controls (P = .005). ALP was elevated in 23% of kava drinkers versus 3% in the
      controls (P = .053). CONCLUSION: Heavy kava beverage consumption was associated
      with significantly elevated GGT levels.

PMID- 17503268
TI  - Gaps in scientific knowledge about the carcinogenic potential of asphalt/bitumen
      fumes.
AB  - Despite a relatively large body of published research, the potential
      carcinogenicity of asphalt/bitumen fumes is still a vexing question. Various
      uncertainties and gaps in scientific knowledge need to be addressed. These
      include uncertainties in chemistry, animal studies, and human studies. The
      chemistry of asphalt/bitumen fumes is complex and varies according to the source
      of the crude oil and the application parameters. The epidemiological studies,
      while showing weak evidence of lung cancer, are inconsistent and many confounding
      factors have not been addressed. Studies of animal exposure are also inconsistent
      regarding laboratory and field-generated fumes. There is a need for further human
      studies that address potential confounding factors such as smoking, diet, coal
      tar, and diesel exposures. Animal inhalation studies need to be conducted with
      asphalt/bitumen fumes that are chemically representative of roofing and paving
      fumes. Underlying all of this is the need for continued characterization of fumes
      so their use in animal and field studies can be properly assessed. Nonetheless,
      uncertainties such as these should not preclude appropriate public health actions
      to protect workers in the even that asphalt fumes are found to be a carcinogenic
      hazard.

PMID- 17503278
TI  - Dermal exposure and urinary 1-hydroxypyrene among asphalt roofing workers.
AB  - The primary objective of this study was to identify significant determinants of
      dermal exposure to polycyclic aromatic compounds (PACs) among asphalt roofing
      workers and use urinary 1-hydroxyprene (1-OHP) measurements to evaluate the
      effect of dermal exposure on total absorbed dose. The study population included
      26 asphalt roofing workers who performed three primary tasks: tearing off old
      roofs (tear-off), putting down new roofs (put-down), and operating the kettle at
      ground level (kettle). During multiple consecutive work shifts (90 workerdays),
      dermal patch samples were collected from the underside of each worker's wrists
      and were analyzed for PACs, pyrene, and benzo(a)pyrene (BAP). During the same
      work week, urine samples were collected at pre-shift, post-shift, and bedtime
      each day and were analyzed for 1-OHP (205 urine samples). Linear mixed effects
      models were used to evaluate the dermal measurements for the purpose of
      identifying important determinants of exposure, and to evaluate urinary 1-OHP
      measurements for the purpose of identifying important determinants of total
      absorbed dose. Dermal exposures to PAC, pyrene, and BAP were found to vary
      significantly by roofing task (tear-off > put-down > kettle) and by the presence
      of an old coal tar pitch roof (pitch > no pitch). For each of the three analytes,
      the adjusted mean dermal exposures associated with tear-off (812 ng PAC/cm2, 14.9
      ng pyrene/cm2, 4.5 ng BAP/cm2) were approximately four times higher than
      exposures associated with operating the kettle (181 ng PAC/cm2, 4.1 ng
      pyrene/cm2, 1.1 ng BAP/cm2). Exposure to coal tar pitch was associated with a 6
      fold increase in PAC exposure (p = 0.0005), an 8-fold increase in pyrene exposure
      (p < 0.0001), and a 35-fold increase in BAP exposure (p < 0.0001). Similarly,
      urinary 1-OHP levels were found to be significantly higher on days when an old
      pitch roof was removed, accounting for a 3.7-fold difference at pre-shift (p =
      0.01), a 5.0-fold difference at post-shift (p = 0.004), and a 7.2-fold difference
      at bedtime (p = 0.002). The pyrene measurements obtained during the work shift
      were found to be strongly correlated with urinary 1-OHP measurements obtained at
      the end of that shift (r = 0.8, p < 0.001) as well as at bedtime (r = 0.7, p <
      0.001). Ultimately, the results of a distributed lag model indicated that dermal
      exposure during the preceding 40 hours had a statistically significant effect on
      urinary 1-OHP. The presence of coal tar pitch was the primary determinant of
      dermal exposure, particularly for exposure to BAP. However, the task-based
      differences that were observed while controlling for pitch suggest that exposure
      to asphalt also contributes to dermal exposures. We found that dermal exposure
      was a significant determinant of total absorbed dose, suggesting that control
      strategies aimed at reducing occupational exposure to PACs should include an
      effort to minimize dermal exposure.

PMID- 17503286
TI  - Physical and chemical characterization of asphalt (bitumen) paving exposures.
AB  - The purpose of this research was to characterize the physical and chemical
      properties of asphalt (bitumen) fume and vapor in hot mix asphalt roadway paving
      operations. Area and personal air samples were taken using real-time equipment
      and extractive sampling and analytical methods to determine worker asphalt
      exposure, as well as to characterize the properties of the particulate and vapor
      phase components. Analysis of personal inhalation and dermal samples by gas
      chromatography/mass spectroscopy showed that the polycyclic aromatic hydrocarbon
      profile is dominated by compounds with molecular weights below 228, and that
      substituted and heterocyclic polycyclic aromatic hydrocarbons comprised
      approximately 71% of the detectable mass concentration (vapor and particulate
      combined). Principal components analysis shows that the polycyclic aromatic
      hydrocarbons with molecular weights greater than 190 are the driving force behind
      the polycyclic aromatic compound exposures measured for the dermal and
      particulate phases; there was no clear trend for the vapor phase Most of the
      aerosol particles are fine (mass median aerodynamic diameter 1.02 microm; count
      median diameter 0.24 microm).

PMID- 17503294
TI  - Effects of cross-sectional dimensions on active noise control in rectangular and
      round ducts.
AB  - Active noise control (ANC) works best to reduce low frequency noise. Because many
      industrial noise sources are broadband, ANC may be used more if it can be
      successfully applied to higher frequency ranges. This study explored one method
      to increase ANC effectiveness at higher frequencies. ANC is particularly useful
      in hard-walled ducts where plane waves propagate. Higher order mode waves are
      much more difficult to control. Basic acoustic principles dictate that the cut-on
      frequency at which higher order modes will first begin to eclipse simple plane
      waves in a duct will be determined by the cross-sectional geometry of the duct.
      The lowest frequency for higher order modes increases as duct diameter decreases;
      therefore the range of frequencies where plane waves dominate will be greater and
      effective control using ANC will be better as duct diameter decreases. The result
      is that somewhat higher frequencies can be controlled with ANC for smaller
      diameters. Below the first higher order mode cut-on frequency for the largest
      size studied, there should be little difference in ANC effectiveness between the
      duct sizes. To test those suppositions, a commercially available ANC system was
      used to reduce random noise in rectangular and round ducts having different
      diameters. Results showed that insertion loss (IL) ranged from 5 dB to 29 dB in
      frequencies ranging from 40-1000 Hz and varied inversely with cross-sectional
      size as expected. There was no difference in IL below 280 Hz (p = 0.7751) between
      the different diameter ducts. There was a significant difference between duct
      diameters above 280 Hz (p < 0.0001). The same tests were conducted on a
      rectangular duct with one cross-sectional dimension fixed and one varied at seven
      different sizes. Results showed similar IL from 5 dB to 29 dB that varied
      inversely with size.

PMID- 17503295
TI  - Effect of physical exertion on the biological monitoring of exposure to various
      solvents following exposure by inhalation in human volunteers: II. n-Hexane.
AB  - This study evaluated the impact of physical exertion on two n-hexane (HEX)
      exposure indicators in human volunteers exposed under controlled conditions in an
      inhalation chamber. A group of four volunteers (two women, two men) were exposed
      to HEX (50 ppm; 176 mg/m(3)) according to several scenarios involving several
      periods when volunteers performed either aerobic (AERO), muscular (MUSC), or both
      AERO/MUSC types of exercise. The target intensities for 30-min exercise periods
      separated by 15-min rest periods were the following: REST, 50W AERO [time
      weighted average intensity including resting period (TWAI): 38W], 50W AERO/MUSC
      (TWAI: 34W), 100W AERO/MUSC (TWAI: 63W), and 100W AERO (TWAI: 71W) for 7 hr (two
      3-hr exposure periods separated by 1 hr without exposure) and 50W MUSC for 3 hr
      (TWAI: 31W). Alveolar air and urine samples were collected at different time
      intervals before, during, and after exposure to measure unchanged HEX in expired
      air (HEX-A) and urinary 2,5-hexanedione (2,5-HD). HEX-A levels during exposures
      involving AERO activities (TWAI: 38W and 71W) were significantly enhanced
      (approximately +14%) compared with exposure at rest. MUSC or AERO/MUSC exercises
      were also associated with higher HEX-A levels but only at some sampling times. In
      contrast, end-of-exposure (7 hr) urinary 2,5-HD (mean +/- SD) was not modified by
      physical exertion: 4.14 +/- 1.51 micromol/L (REST), 4.02 +/- 1.52 micromol/L
      (TWAI 34W), 4.25 +/- 1.53 micromol/L (TWAI 38W), 3.73 +/- 2.09 micromol/L (TWAI
      63W), 3.6 +/- 1.34 micromol/L (TWAI 71W) even though a downward trend was
      observed. Overall, this study showed that HEX kinetics is practically insensitive
      to moderate variations in workload intensity; only HEX-A levels increased
      slightly, and urinary 2,5-HD levels remained unchanged despite the fact that all
      types of physical exercise increased the pulmonary ventilation rate.

PMID- 17503296
TI  - Comparison of detection methods for Aspergillus fumigatus in environmental air
      samples in an occupational environment.
AB  - Methods to study occupational exposures to fungi and fungal materials in
      facilities where the dominant exposure is the pathogenic and allergenic fungus
      Aspergillus fumigatus are lacking. Air samples were collected near a conveyor in
      a wood chip recycling plant to compare methods that might be used to assess
      exposure to A. fumigatus or suitable proxies. These included total dust mass,
      total intact spores, culturable propagules growing > 35 degrees C, ergosterol, A.
      fumigatus allergen Asp f1, and quantitative polymerase chain reaction for A.
      fumigatus. Of these measurements, Asp f1 showed the most promise based on its
      relative response to measurements where there is a long history of use in
      industrial hygiene practice (total mass, ergosterol, total intact spores,
      culturable propagules).

PMID- 17503297
TI  - Heavy equipment maintenance exposure assessment: using a time-activity model to
      estimate surrogate values for replacement of missing data.
AB  - This study on four pieces of heavy construction equipment was conducted to
      determine the concentration of airborne asbestos fibers during in-frame
      maintenance and repair activities, which included aggressive techniques that
      resulted in visible dust from work involving friction products and gaskets.
      Despite execution of a carefully planned sampling strategy, approximately 10%
      (47) of the samples collected could not be analyzed due to overloading or filter
      damage. To include the overloaded samples in the data analysis, surrogate values
      were estimated following a time-activity model. Twelve long-term personal
      samples, 2 short-term, 30-min personal samples, and 31 long-term area samples
      were modeled. Personal and area time-weighted average (TWA) data were analyzed
      both with and without the estimated surrogate values and compared. A total of 444
      samples were collected over 9 days. Four experienced heavy equipment mechanics
      removed and replaced friction products and gaskets. Samples were analyzed using
      NIOSH Method 7400 Phase Contrast Microscopy followed by NIOSH Method 7402
      Transmission Electron Microscopy. Sample data information including the surrogate
      values for the full-shift, TWA personal sample results ranged from 0.002 to 0.064
      asbestos f/cc. Personal, short-term, 30-min sample results, including the two
      surrogate values, ranged from 0.038 to 0.561 asbestos f/cc. Full-shift TWA area
      samples, including the 31 surrogate values, ranged from 0.005 to 0.039 asbestos
      f/cc. Area air sample results at the end of the project were similar to levels
      measured before the start of the project. No fiber concentration buildup within
      the work area was indicated over the 9-day study. All full-shift personal and
      area TWA sample results were below 0.1 f/cc, and short-term 30-min personal
      samples were below 1.0 f/cc. Statistical results of the sample data with and
      without the surrogate values were consistent. Use of the time-activity model
      reduced the uncertainty associated with this data analysis and provided a
      consistent logical process for estimating surrogate values to replace missing
      data.

PMID- 17503298
TI  - Decreased risk of complications with bilateral thoracoscopy and left-to-right
      mediastinal dissection during minimally invasive repair of pectus excavatum.
AB  - INTRODUCTION: The repair of pectus excavatum using minimally invasive surgery is
      widely gaining acceptance as an equal if not superior technique to the
      traditional open approach. A number of modifications to the original Nuss
      procedure have been proposed to avoid complications. PURPOSE OF THE STUDY: The
      aim of the study was to confirm the efficacy and safety of left-to-right
      mediastinal dissection during a Nuss procedure. METHODS: A retrospective review
      of modified thoracoscopic Nuss repairs of pectus excavatum done at the Children's
      Hospital Oakland over approximately a 5-year period with subsequent data analysis
      was performed. RESULTS: Thirty-two patients between the ages of 3 and 19
      underwent a modified Nuss procedure using bilateral thoracoscopy and left-to
      right mediastinal dissection. No intra- or postoperative complications were noted
      in any of the patients, which included but were not limited to mediastinal
      injury, bleeding, or chest tube insertion for pneumothorax. CONCLUSIONS:
      Bilateral thoracoscopic repair of pectus excavatum with left-to-right mediastinal
      dissection is a safe alternative to the traditional approach, as it allows a more
      complete visualization of the mediastinum and eliminates the need for additional
      safety measures such as subxiphoid dissection and elevation.

PMID- 17503299
TI  - The relevance of surgical therapy for bilateral and/or multiple pulmonary
      metastases in children.
AB  - PURPOSE: Pulmonary surgery is frequently used for the treatment of metastases in
      children with various malignant diseases. The benefit of an aggressive surgical
      treatment in children with bilateral and/or multiple pulmonary metastases is
      still discussed controversially. METHODS: A retrospective analysis of 10 children
      (7 girls, 3 boys; age range from 2 to 16.5 years) who underwent thoracotomy for
      bilateral and/or multiple pulmonary metastases was performed. The primary
      malignancies were osteosarcoma (n = 4), hepatoblastoma (n = 3), malignant
      peripheral nerve sheath tumor (n = 1), adrenocortical carcinoma (n = 1) and
      alveolar rhabdomyosarcoma (n = 1). Unilateral but multiple pulmonary metastases
      were found in 3 children. 7 patients showed bilateral pulmonary metastases.
      Preoperative induction chemotherapy with tumor regression and a subsequent
      decrease in the size and number of pulmonary metastases was mandatory for the
      surgery of metastases. RESULTS: Standardized bilateral thoracotomy was performed
      in 4 patients in 1 operation (in 1 patient combined with a hemihepatectomy), and
      in 3 patients, in 2 operations on different days. 5 children underwent re
      thoracotomy due to recurrent pulmonary metastases (2 patients: unilateral; 3
      patients: bilateral; 1 patient: twice bilateral). All visible and palpable
      metastases (1 - 25) were excised, either by wedge resection, by segment resection
      or by lobectomy. Postoperative artificial ventilation was necessary for 0 to 24
      hours. Postoperative complications included intrathoracic secondary hemorrhage in
      3 cases and pneumonia in 1 patient. 2 patients (20%) died of recurrent metastatic
      disease (osteosarcoma: 1; adrenocortical carcinoma: 1). During a mean follow-up
      period of 49 months (14 to 66 months after the last thoracotomy), 8 patients
      (80%) remained in complete remission without clinically relevant respiratory
      restrictions. CONCLUSION: Complete surgical resection of pulmonary metastases
      after response to induction chemotherapy may increase survival in carefully
      selected children, even in cases with multiple and recurrent metastatic disease.
      In children, bilateral thoracotomy within a single operation is possible without
      an increased complication rate.

PMID- 17503301
TI  - Significance of the anomalous arrangement of the pancreaticobiliary duct in the
      etiology of biliary atresia.
AB  - BACKGROUND/PURPOSE: The anomalous arrangement of the pancreaticobiliary duct
      (AAPBD) is one theory used to explain the etiology of biliary atresia. We
      investigated whether AAPBD could be involved and evaluated its significance for
      the etiology of biliary atresia. MATERIALS AND METHODS: Of 43 patients with
      biliary atresia, the area between the common bile duct and the duodenum could be
      visualized by operative cholangiogram in 5 patients with an uncorrectable type of
      biliary atresia. Three of the 5 showed an anomalous arrangement of the
      pancreaticobiliary duct. In these 3 patients, the type of anomalous arrangement
      of the pancreaticobiliary duct and the length of the common channel were studied
      by operative cholangiogram. Histological findings of the gallbladder and the
      common bile duct were examined in addition to the measurement of the serum
      amylase levels. RESULTS: All 3 patients showed AAPBD with the P-C type of
      pancreaticobiliary junction. The length of the common channel ranged from 7 mm to
      12 mm. Two of the 3 cases did not show an elevated serum amylase level.
      Epithelial hyperplasia of the gallbladder was observed in one patient, while the
      other two showed no hyperplasia. Inflammatory changes in the mucosa of the
      gallbladder and the common bile duct were not remarkable in these 3 patients.
      CONCLUSIONS: From these results it seems that AAPBD in biliary atresia might not
      be an etiological factor for atresia of the extrahepatic bile duct, but might be
      an associated anomaly in biliary atresia. Other factors should be examined to
      clarify the etiological factor leading to lumenal obstruction of the extrahepatic
      bile duct.

PMID- 17503300
TI  - Paediatric blunt abdominal trauma: challenges of management in a developing
      country.
AB  - BACKGROUND: In developed countries, the availability of advanced imaging
      techniques has reduced the necessity for laparotomy following blunt abdominal
      trauma in children. Laparotomy rates still remain high in developing countries
      where these advanced imaging techniques are lacking. A simple management protocol
      to identify patients who require laparotomy could reduce the laparotomy rate in
      children with blunt abdominal trauma in these countries. PATIENTS/METHODS: This
      is a review of children aged 15 years or below managed in our institution over a
      5 1/2-year period for blunt abdominal trauma. The children were divided into two
      groups. Group A consisted of children managed from January 1999 - December 2000.
      During this period, there was no protocol. Group B consisted of children managed
      from January 2001 - June 2004. During this period, a simple management protocol
      was introduced. The laparotomy rates in the two groups were analysed using a
      simple chi-square. RESULTS: A total of 48 children, representing 63 % of children
      with abdominal trauma during the study period, were examined (Group A 17; Group B
      31). Their ages ranged from 1.5 years - 15 years (median 9 years). Thirty-four
      were boys, 14 were girls (M:F = 2.4:1). Road traffic accidents accounted for 38
      (79.1 %) and falls from heights for 9 cases (18.75 %), and one boy with a
      hydronephrotic kidney fell off the staircase at home. The diagnosis was clinical,
      supported by abdominal ultrasound scan (USS) and plain abdominal film. Twenty
      eight (58.3 %) children had laparotomy (15 in Group A; 13 in Group B). There was
      a statistically significant difference in the laparotomy rates between Group A
      and B (p < 0.01). Nineteen children were managed nonoperatively (2 in Group A; 17
      in Group B); one child died before an operation could be performed. There were 59
      abdominal organ injuries in 45 children. In 2 children, ultrasound could not
      diagnose any organ injury. There were 33 splenic injuries; 15 children had
      splenic conservation, 7 underwent a splenectomy, while 10 were managed
      nonoperatively. One child with splenic injury died before operation. Of 7 liver
      injuries, 4 required suturing of lacerations, 1 subcapsular haematoma was left
      undisturbed at laparotomy, while 2 were managed nonoperatively. There were 4
      pancreatic injuries. Three were managed nonoperatively, while 1 associated with
      duodenal injury had a laparotomy. All 6 gastrointestinal injuries had laparotomy.
      There were 5 renal injuries: 3 had laparotomy with suturing, while 2 were managed
      nonoperatively. There were 4 bladder injuries: 2 had laparotomy with suprapubic
      catheter insertion, while 2 were managed nonoperatively. There were 7
      retroperitoneal haematomas in association with other organ injuries. Associated
      injuries included head injury in 2, long bone fracture in 2, spinal injury and
      chest trauma in 1 each. There were 4 deaths, 1 before surgery could be performed.
      CONCLUSION: Blunt abdominal trauma in children resulted mainly from road traffic
      accidents. The use of a simple protocol supported by ultrasound scan could reduce
      the laparotomy rate in countries with limited facilities.

PMID- 17503302
TI  - The significance of steroid therapy after hepatoportoenterostomy in infants with
      biliary atresia.
AB  - PURPOSE: Despite improvements in the surgical management of biliary atresia (BA),
      it is still difficult to maintain good bile flow. In the present study, we
      examined steroid therapy and determined the appropriate dose to achieve freedom
      from jaundice after hepatoportoenterostomy (HPE) in the uncorrectable type of BA.
      METHODS: A retrospective clinical analysis was done in 23 of 29 (79 %) cases who
      had become jaundice-free after undergoing HPE with steroid therapy between 1988
      and 2004. A correlation between the total or mean steroid dose and the
      postoperative jaundice period (serum total bilirubin > 1.0 mg/dl) was evaluated
      using linear regression analysis. The regimen was as follows: prednisolone was
      given intravenously, starting with 3 to 5 mg/kg/day, and then gradually tapered
      with repetition until freedom from jaundice was achieved. RESULTS: Age at HPE was
      72 +/- 20 days (mean +/- SD), and the postoperative jaundice period was 108 +/-
      68 days. Total and mean steroid doses were 118 +/- 73 mg/kg and 1.31 +/- 0.8
      mg/kg/day, respectively. There was no correlation between the total steroid dose
      and the period of jaundice. However, there was a significant correlation between
      the mean steroid dose and the period of jaundice (p = 0.021). CONCLUSION: A high
      mean dose of steroids could shorten the jaundice period after HPE in the
      uncorrectable type of BA.

PMID- 17503303
TI  - Post-appendectomy intra-abdominal abscesses--can they successfully be managed
      with the sole use of antibiotic therapy?
AB  - PURPOSE: Controversy persists concerning the management of post-appendectomy
      intra-abdominal abscesses. We hypothesised that most of these abscesses can be
      successfully managed by antibiotic treatment alone, avoiding the complications of
      surgical treatment. METHODS: Hospital records of children treated in our unit for
      intra-abdominal post-appendectomy abscesses over a 6-year period were reviewed
      retrospectively. RESULTS: This study investigates a series of 26 children from 2
      to 15 years of age presenting with one or more post-appendectomy intra-abdominal
      abscesses. After an average delay of 7 days after initial surgery, 23 children
      had developed an isolated abscess, while 3 children had multiple abscesses.
      Twenty-two patients (84.8 %) were treated conservatively by intravenous triple
      antibiotic therapy alone. Complete clinical, radiological and biological
      resolution of the abscesses was obtained in all of these children after a mean
      hospitalisation of 8 days. Four children (15.2 %) were treated surgically: three
      children with a stable patient status and one child with septic shock requiring
      urgent surgery. CONCLUSION: The results suggest that intravenous triple
      antibiotic therapy alone is an efficacious first-line treatment in children
      developing intra-abdominal abscesses following appendectomy. Surgical
      intervention is rarely necessary except in patients with an alarming patient
      status or with signs of septic shock.

PMID- 17503304
TI  - The efficacy of conservative treatment for late term ovarian torsion.
AB  - BACKGROUND/PURPOSE: Recent reports have focused on detorsion after ovarian
      torsion in the literature. The aim of the study was to investigate late term
      changes in both ovaries after delayed detorsion following ovarian torsion in
      rats. MATERIALS: Female, prepubertal, Wistar albino rats were divided into four
      groups (n = 6/group). The left ovaries were used for the study and the right
      ovaries were kept as the control. The groups were constituted as follows: Group
      1: left ovarian fixation, bilateral oophorectomy 48 hours later; Group 2: left
      ovarian torsion and fixation, bilateral oophorectomy 48 hours later; Group 3:
      detorsion 48 hours after torsion and bilateral oophorectomy after another 48
      hours; Group 4: detorsion 48 hours after torsion and bilateral oophorectomy after
      21 days. The total injury score (TIS) was compiled histologically in a double
      blind fashion. Congestion, edema, bleeding and polymorphonuclear lymphocyte
      infiltration were assessed for TIS. RESULTS: The TIS was found to be 8 points in
      Group 1; 38 in Group 2; 28 in Group 3 and 12 in Group 4, respectively. The TIS
      was based on results from the left ovaries in Group 1, whereas 31 points were
      attributable to the left ovaries and 7 to the right ovaries in Group 2. In Groups
      3 and 4, TIS points were the same in both study and control ovaries. The
      difference between the left ovaries of Groups 1 and 2 and the left ovaries of
      Groups 2 and 4 was statistically significant (p < 0.05). CONCLUSION: Viable
      ovarian tissue can be detected even after 48 hours of torsion, which is a
      relatively long period of ischemia. Tissue injury decreases significantly after
      detorsion during late recovery. In view of previous case reports in the
      literature and the present findings, detorsion is recommended in children with
      ovarian torsion regardless of the ischemic period and/or macroscopic appearance.

PMID- 17503305
TI  - Effects of herbal medicine Dai-Kenchu-to on anorectal function in children with
      severe constipation.
AB  - AIM: We administered the herbal medicine Dai-Kenchu-To (DKT) to children with
      severe chronic constipation or with severe constipation after surgery for
      anorectal malformations. We then objectively assessed the effect of DKT on
      anorectal function by manometric study in addition to using a clinical scoring
      system. PATIENTS AND METHODS: Ten children with severe chronic constipation and 5
      children with severe constipation after surgery for anorectal malformations were
      assessed. These 15 children received 0.3 g/kg/day of DKT for periods ranging from
      3 months to 1 year. We objectively assessed their bowel function, sphincter
      function and rectal reservoir function by anorectal manometry and clinical
      scoring. RESULTS: In 10 children with severe chronic constipation, the clinical
      score after administration of DKT (7.2 +/- 0.8) improved significantly compared
      with that before administration of DKT (4.6 +/- 2.9) (p < 0.02). The threshold
      sensation volume and the maximum tolerable volume after administration of DKT
      significantly (p < 0.05; p < 0.01) decreased (128 +/- 63 ml vs. 69 +/- 18 ml; 229
      +/- 99 ml vs. 144 +/- 47 ml), and rectal compliance after administration of DKT
      also significantly (p < 0.05) decreased (12.4 +/- 10.9 ml/cmH(2)O vs. 4.7 +/- 3.9
      ml/cmH(2)O). CONCLUSION: The present study demonstrated that DKT had a favorable
      clinical effect on severe constipation in children, and anorectal manometry
      showed an improvement in their rectal reservoir functions. It appears that the
      results were secondary to DKT-stimulated peristalsis of the intestine, which
      promoted regular bowel habits.

PMID- 17503306
TI  - Bladder augmentation and/or continent urinary diversion: 10-year experience.
AB  - OBJECTIVE: We evaluated the success and the long-term complications associated
      with augmentation cystoplasty and/or continent urinary diversion in children with
      urinary incontinence due to neurogenic or malformed bladder. MATERIALS AND
      METHODS: The records of 23 patients (12 females, 11 males) who underwent such
      procedures between 1994 and 2004 were reviewed retrospectively. The most common
      type of augmentation cystoplasty was ileocystoplasty. The most common type of
      conduit for the urinary continent diversion was appendicovesicostomy. Combined
      bladder neck closure was not performed systematically. Neocystoureterostomy was
      done in 14 refluxing ureters. RESULTS: Of the 21 patients who underwent
      augmentation cystoplasty, only one was incontinent after the procedure and
      required reconstruction of the bladder neck using the Young-Dees procedure. The
      most common complications were stomal stenosis and bladder stone formation.
      CONCLUSION: Augmentation cystoplasty and continent urinary diversion procedures
      can increase the functional capacity of the small bladder and allow the majority
      of patients to achieve continence while preserving renal function. Combined
      bladder neck closure is not necessary to obtain urinary continence; on the
      contrary, it eliminates a useful pop-off mechanism. Neocystouretrostomy is not
      required for every refluxing ureter unless it can be performed on the original
      bladder. Bladder stones and stomal stenosis are the most significant long-term
      complications in these patients.

PMID- 17503307
TI  - Management of hydrocephalus in children with plasminogen deficiency.
AB  - Congenital plasminogen deficiency is an infrequent disorder, which usually
      becomes symptomatic as ligneous conjunctivitis. However, pseudomembranous lesions
      in the mucosa of the pharynx, tracheobronchial tree, and the peritoneum may
      likewise occur. An accompanying hydrocephalus is extremely rare; only 16 cases
      have been reported to date. The reports indicate that hydrocephalus, even if
      treated by ventriculoperitoneal (VP) cerebrospinal fluid (CSF) shunting, worsens
      the prognosis substantially. Thus, VP CSF shunting does not seem to be the
      optimal therapy for hydrocephalic children with plasminogen deficiency. We add
      two cases to the literature, and, on the base of our experience, we propose a
      management strategy for the hydrocephalus. We report the case history of two
      children with plasminogen deficiency and associated hydrocephalus. Both children
      initially were treated with VP shunts and had a very similar clinical course with
      multiple shunt malfunctions due to nonabsorption by the peritoneum. In the first
      child, the attempt to treat the hydrocephalus with a ventriculoatrial (VA) shunt
      failed due to catheter thrombosis. Finally, a ventriculocholecystic shunt was
      placed in both children, which worked well. In patients with plasminogem
      deficiency and associated hydrocephalus, special care must be taken in the
      management of hydrocephalus. The absorptive capacity of the peritoneum is reduced
      by pseudomembrane formation, which results in VP shunt malfunction. The
      plasminogen deficiency results in early thrombus formation if atrial catheters
      are used. Therefore, the authors believe that ventriculocholecystic shunting
      should be considered early on in the course of the disease.

PMID- 17503308
TI  - Haemothorax caused by isolated costal exostosis.
AB  - We report an unusual case of spontaneous haemothorax in a 13-year-old girl with
      isolated costal exostosis. Surgical excision of the exostosis was performed with
      complete resolution. Costal exostosis should be considered in the differential
      diagnosis of spontaneous haemothorax in children in order to avoid unnecessary
      investigation and to establish an adequate treatment plan.

PMID- 17503309
TI  - Spontaneous perforation of the extrahepatic bile duct in infancy: report of two
      cases and literature review.
AB  - BACKGROUND: Spontaneous perforation of the bile duct (SPBD) is a rare disease in
      infancy. The pathogenesis, diagnostic modalities and treatment options for this
      condition are reviewed and discussed. METHODS: The authors report 2 new
      observations of SPBD in 2 male newborns aged respectively 27 and 21 days.
      RESULTS: The 2 newborns presented with cholestatic jaundice. Abdominal sonography
      showed an extrahepatic mass. Exploratory laparotomy revealed that the perforation
      was located in the cystic duct in the first case and in the common bile duct
      (CBD) in the second. The site of perforation was repaired and both patients
      underwent simple external biliary drainage. The postoperative course was
      uneventful for both patients with follow-up ranging from 2 to 4 years.
      CONCLUSIONS: SPBD is a rare, but important cause of surgical jaundice in infants.
      The pathogenesis of SPBD is unknown and multifactorial and diagnosis is often
      problematic. Surgical management is always required and a conservative approach
      is usually recommended. The prognosis is good with early surgical management.

PMID- 17503310
TI  - Perineal lipoma in a newborn boy--a case report.
AB  - We report the case of a newborn presenting with a pediculated mass arising from
      the anal margin. Antenatal sonogram and magnetic resonance imaging were unable to
      diagnose the precise nature of the lesion. Sacrococcygeal teratoma, an
      enterogenous cyst, a polyp, a prolapse or other perineal tumors were all proposed
      as possible entities. At birth, no other anatomic anomaly than this homogenous 2
      cm para-anal lesion was seen. Excision of the mass was performed under general
      anesthesia. The postoperative histological exam showed mature fat cells.
      Reviewing the literature, there have been few previously reported cases of
      congenital perineal lipoma. It is a rare, benign and easy-to-treat condition that
      can be evocated by morphological sonography or magnetic resonance imaging (MRI).

PMID- 17503311
TI  - Retroperitoneal abscess from dropped appendicolith complicating laparoscopic
      appendectomy.
AB  - Abscesses can occur after appendectomy. With the increasing use of laparoscopy,
      this risk has increased in the same way as the incidence of abscesses related to
      dropped gallstones increased after laparoscopic cholecystectomy. However, this
      occurrence has been rarely reported. We describe here the case of a young patient
      who developed retroperitoneal abscess one year after laparoscopic appendectomy.

PMID- 17503312
TI  - Fibroepithelial polyps causing ureteropelvic junction obstruction in children--a
      case report and review article.
AB  - Fibroepithelial polyps are extremely rare benign mesodermal tumours in children
      that can cause ureteropelvic junction (UPJ) obstruction. We report on a 10-year
      old boy presenting with UPJ obstruction due to a fibroepithelial polyp, and
      review 28 similar published paediatric cases.

PMID- 17503313
TI  - An update on the treatment of high-risk hemangiomas in infants.

PMID- 17503314
TI  - [Socio-economical aspects, quality of life and state of knowledge in hepatitis B
      patients. Socio-economical aspects in hepatitis B].
AB  - BACKGROUND: Little is known about socio-economical consequences and information
      status of patients with chronic hepatitis B virus (HBV) infection. AIMS AND
      METHODS: The present study prospectively analyzed questionnaires about socio
      economical consequences and information status including the SF12 quality-of-life
      analysis in HBV-infected subjects. Overall 1500 questionnaires were distributed
      by clinics, practioners, patient support groups and internet; 255 questionnaires
      were sent back. Results were compared with a recent study in 714 HCV infected
      patients (Z Gastroenterol 2006; 44: 305-317). RESULTS: HBV-infected patients were
      younger (mean 46 vs. 52 years), more likely to be male (62 vs. 44%) and to come
      from abroad (30 vs. 9%) when compared with HCV-infected subjects. Only 1 and 4%
      of HBV- and HCV-infected subjects, respectively, considered the public
      information about hepatitis as good or very good, 73 and 77%, however, as bad or
      very bad. Mental and physical quality-of-life (SF12) was better in HBV- than in
      HCV-infected subjects, but reduced when compared with a sex- and age-matched
      general population (p < 0.001). Quality-of-life decreased with increases in HBV
      DNA, fibrosis and inflammation. In both HBV- and HCV-infected subjects there were
      information deficits concerning the risks for infection; some of these were more
      pronounced in HBV-infected subjects when compared to HCV-infected ones. German
      subjects with HBV and HCV infection are in general well informed about their
      infection (73-87% knew ALT and histology results); however, HBV-infected subjects
      are less well informed in particular about viral load and HBeAg (59 and 30%) when
      compared with HCV infected subjects who knew HCV-RNA and genotype in 80-85%.
      CONCLUSIONS: The information deficits about viral load are of concern for HBV
      infected subjects because these data are more important in HBV than in HCV
      infection. This lack of information likely reflects a lack of attentiveness
      towards HBV-DNA levels by the patients' physician. Both HBV- and HCV-infected
      subjects have problems at work and with various insurances; both have a reduced
      quality-of-life which correlates with viral load and degree of inflammation and
      fibrosis. Both populations consider the public information status about viral
      hepatitis to be bad.

PMID- 17503315
TI  - Octreotide alone or in combination with rofecoxib as palliative treatment for
      advanced hepatocellular cancer.
AB  - BACKGROUND: Median survival for advanced hepatocellular carcinoma (HCC) is around
      3 months. Previous octreotide-based treatment studies revealed conflicting
      results. AIMS AND METHODS: To determine whether palliative treatment for HCC is
      beneficial in terms of survival and quality of life (primary outcome measures).
      Patients were prospectively randomised to receive open-label octreotide 30 mg
      monthly alone (n = 39) or in combination with rofecoxib (up to 50 mg bid daily, n
      = 32) for a minimum of six months, or until death occurred. RESULTS: Median
      overall survival (154 days) and time to progression (94 days) were similar for
      both treatments and within the range of published trials for octreotide, while
      adding rofecoxib to octreotide did not alter overall survival (149 vs. 155 days,
      p = 0.849). Treatment-associated clinical benefit was seen in 16/71 patients (3
      patients with partial remissions and 13 with stable disease). Delay in tumor
      progression was associated with prolonged median survival (p < 0.0001) and a
      better quality of life (p < 0.05). Moreover, survival outcome was associated with
      a CLIP score < 3, extent of portal vein infiltration, well-differentiated tumor
      histology, prothrombin time, alkaline phosphatase, bilirubin, serum ferritin, and
      gamma-glutamyltransferase (p < 0.01 each). DISCUSSION: Rofecoxib added to
      octreotide treatment did not improve survival over octreotide treatment alone.
      Octreotide treatment, although without major side effects, cannot be recommended
      in general as monotherapy, unless the few patients responding can better be
      characterised. There may still be a role for combining octreotide with other
      emerging targeted therapies because of potentially synergistic modes of action.

PMID- 17503316
TI  - Onerous concomitant complications of ulcerative colitis: a case report.
AB  - Ulcerative colitis is a chronic inflammatory disease of the colon characterized
      by intermittent exacerbations and remissions. It may be complicated with colon
      cancer or autoimmune-related extracolonic problems. Herein, we present a woman
      with ulcerative colitis who developed sarcoidosis, colon cancer, primary
      sclerosing cholangitis, and cholangiocarcinoma. To our knowledge, such
      associations in a patient have not been reported before.

PMID- 17503317
TI  - Unusual treatment of a gastric marginal zone B-cell lymphoma of MALT type.
AB  - Patients with gastric marginal zone-B-cell lymphoma of MALT-type of stage I are
      usually treated by eradication therapy as Helicobacter pylori infection is
      evident in the majority (> 90%) of them. In case of a negative Helicobacter
      pylori status, if the lymphoma does not reveal regression after successful
      eradication of the bacterium, or in stage II, radiation is nowadays the treatment
      of choice. Gastrectomy is only reserved for special conditions such as
      endoscopically not treatable bleeding or patient's explicit request. All
      treatment modalities follow a curative intention. We here report on a patient
      with a Helicobacter pylori negative MALT lymphoma of stage I presenting as a
      localized polypoid lesion in the gastric fundus. Radiotherapy was indicated.
      However, the patient refused this standard therapy as well as surgical resection
      as a possible alternative. When signs of lymphoma progression became evident we
      performed an endoscopy-assisted laparoscopic resection of the fundus which
      resulted in a continuing lymphoma-free condition. Thus, local treatment
      modalities such as endoscopic mucosal resection or laparoscopic resection may
      represent a therapeutic option in case of a localized lymphoma finding in the
      individual patient who is not suitable for or who refuse standard therapeutic
      approaches.

PMID- 17503318
TI  - [Transient elastography (FibroScan) for the non-invasive assessment of liver
      fibrosis: current status and perspectives].
AB  - A precise staging of the degree of liver fibrosis is important for the estimation
      of prognosis, surveillance and treatment decision in patients with chronic liver
      diseases. At present, liver biopsy is still the reference standard for the
      assessment of liver fibrosis. However, it is an invasive method associated with
      patient discomfort and in rare cases with serious complications. In addition, the
      accuracy of liver biopsy is limited due to intra- and interobserver variability
      and sampling errors. Non-invasive markers and methods for the assessment of liver
      fibrosis have been intensively evaluated in many studies. The FibroScan
      (Echosens, France) uses the transient elastography principle for the measurement
      of liver stiffness. At present (January 2007), studies evaluating the FibroScan
      in a wide range of liver diseases have been published in 20 full papers and 76
      abstracts. The present review gives an overview of the current literature. The
      best results are reported for the differentiation between cirrhosis and no
      cirrhosis. With the combination of FibroScan and non-invasive serum fibrosis
      markers, the accuracy for the diagnosis of significant fibrosis (Metavir F > or =
      2) can be further improved. According to recent data the FibroScan can also be
      useful for the evaluation of treatment response in patients receiving antiviral
      treatment for chronic hepatitis C. In addition, several studies have shown, that
      the FibroScan can be applied to estimate the risk of complications associated
      with liver cirrhosis.

PMID- 17503319
TI  - [News from the Cochrane Library: Maintenance of remission in ulcerative colitis].

PMID- 17503320
TI  - [Anorectal manometry].
AB  - This document contains the guidelines of the German Societies of
      Neurogastroenterology and Motility, Gastroenterology (committee for proctology),
      Abdominal Surgery (coloproctology working group), and Coloproctology for
      anorectal manometry in adults. Recommendations are given about technical notes,
      study preparation (equipment; patient), technique for performing manometry and
      data analysis, reproducibility, and indications. Minimum standards for anorectal
      manometry are measurement of resting and squeeze pressure, testing of rectoanal
      inhibitory reflex, determination of rectal sensation (first perception and urge),
      and calculation of rectal compliance. Anorectal manometry is indicated in
      patients with fecal incontinence and constipation in the context of a structured
      programme.

PMID- 17503321
TI  - [Erosions in esophageal reflux disease and Barrett neoplasia are found most
      frequently close to the right esophageal wall].

PMID- 17503322
TI  - A genomewide admixture map for Latino populations.
AB  - Admixture mapping is an economical and powerful approach for localizing disease
      genes in populations of recently mixed ancestry and has proven successful in
      African Americans. The method holds equal promise for Latinos, who typically
      inherit a mix of European, Native American, and African ancestry. However,
      admixture mapping in Latinos has not been practical because of the lack of a map
      of ancestry-informative markers validated in Native American and other
      populations. To address this, we screened multiple databases, containing millions
      of markers, to identify 4,186 markers that were putatively informative for
      determining the ancestry of chromosomal segments in Latino populations. We
      experimentally validated each of these markers in at least 232 new Latino,
      European, Native American, and African samples, and we selected a subset of 1,649
      markers to form an admixture map. An advantage of our strategy is that we focused
      our map on markers distinguishing Native American from other ancestries and
      restricted it to markers with very similar frequencies in Europeans and Africans,
      which decreased the number of markers needed and minimized the possibility of
      false disease associations. We evaluated the effectiveness of our map for
      localizing disease genes in four Latino populations from both North and South
      America.

PMID- 17503323
TI  - Gene copy-number variation and associated polymorphisms of complement component
      C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor
      for and high copy number is a protective factor against SLE susceptibility in
      European Americans.
AB  - Interindividual gene copy-number variation (CNV) of complement component C4 and
      its associated polymorphisms in gene size (long and short) and protein isotypes
      (C4A and C4B) probably lead to different susceptibilities to autoimmune disease.
      We investigated the C4 gene CNV in 1,241 European Americans, including patients
      with systemic lupus erythematosus (SLE), their first-degree relatives, and
      unrelated healthy subjects, by definitive genotyping and phenotyping techniques.
      The gene copy number (GCN) varied from 2 to 6 for total C4, from 0 to 5 for C4A,
      and from 0 to 4 for C4B. Four copies of total C4, two copies of C4A, and two
      copies of C4B were the most common GCN counts, but each constituted only between
      one-half and three-quarters of the study populations. Long C4 genes were strongly
      correlated with C4A (R=0.695; P<.0001). Short C4 genes were correlated with C4B
      (R=0.437; P<.0001). In comparison with healthy subjects, patients with SLE
      clearly had the GCN of total C4 and C4A shifting to the lower side. The risk of
      SLE disease susceptibility significantly increased among subjects with only two
      copies of total C4 (patients 9.3%; unrelated controls 1.5%; odds ratio [OR] =
      6.514; P=.00002) but decreased in those with > or =5 copies of C4 (patients
      5.79%; controls 12%; OR=0.466; P=.016). Both zero copies (OR=5.267; P=.001) and
      one copy (OR=1.613; P=.022) of C4A were risk factors for SLE, whereas > or =3
      copies of C4A appeared to be protective (OR=0.574; P=.012). Family-based
      association tests suggested that a specific haplotype with a single short C4B in
      tight linkage disequilibrium with the -308A allele of TNFA was more likely to be
      transmitted to patients with SLE. This work demonstrates how gene CNV and its
      related polymorphisms are associated with the susceptibility to a human complex
      disease.

PMID- 17503324
TI  - Transcriptional control of SLC26A4 is involved in Pendred syndrome and
      nonsyndromic enlargement of vestibular aqueduct (DFNB4).
AB  - Although recessive mutations in the anion transporter gene SLC26A4 are known to
      be responsible for Pendred syndrome (PS) and nonsyndromic hearing loss associated
      with enlarged vestibular aqueduct (EVA), also known as "DFNB4," a large
      percentage of patients with this phenotype lack mutations in the SLC26A4 coding
      region in one or both alleles. We have identified and characterized a key
      transcriptional regulatory element in the SLC26A4 promoter that binds FOXI1, a
      transcriptional activator of SLC26A4. In nine patients with PS or nonsyndromic
      EVA, a novel c.-103T-->C mutation in this regulatory element interferes with
      FOXI1 binding and completely abolishes FOXI1-mediated transcriptional activation.
      We have also identified six patients with mutations in FOXI1 that compromise its
      ability to activate SLC26A4 transcription. In one family, the EVA phenotype
      segregates in a double-heterozygous mode in the affected individual who carries
      single mutations in both SLC26A4 and FOXI1. This finding is consistent with our
      observation that EVA occurs in the Slc26a4(+/-); Foxi1(+/-) double-heterozygous
      mouse mutant. These results support a novel dosage-dependent model for the
      molecular pathogenesis of PS and nonsyndromic EVA that involves SLC26A4 and its
      transcriptional regulatory machinery.

PMID- 17503325
TI  - Red-green color vision impairment in Duchenne muscular dystrophy.
AB  - The present study evaluated the color vision of 44 patients with Duchenne
      muscular dystrophy (DMD) (mean age 14.8 years; SD 4.9) who were submitted to a
      battery of four different color tests: Cambridge Colour Test (CCT), Neitz
      Anomaloscope, Ishihara, and American Optical Hardy-Rand-Rittler (AO H-R-R).
      Patients were divided into two groups according to the region of deletion in the
      dystrophin gene: upstream of exon 30 (n=12) and downstream of exon 30 (n=32). The
      control group was composed of 70 age-matched healthy male subjects with no
      ophthalmological complaints. Of the patients with DMD, 47% (21/44) had a red
      green color vision defect in the CCT, confirmed by the Neitz Anomaloscope with
      statistical agreement (P<.001). The Ishihara and the AO H-R-R had a lower
      capacity to detect color defects--5% and 7%, respectively, with no statistical
      similarity between the results of these two tests nor between CCT and
      Anomaloscope results (P>.05). Of the patients with deletion downstream of exon
      30, 66% had a red-green color defect. No color defect was found in the patients
      with deletion upstream of exon 30. A negative correlation between the color
      thresholds and age was found for the controls and patients with DMD, suggesting a
      nonprogressive color defect. The percentage (66%) of patients with a red-green
      defect was significantly higher than the expected <10% for the normal male
      population (P<.001). In contrast, patients with DMD with deletion upstream of
      exon 30 had normal color vision. This color defect might be partially explained
      by a retina impairment related to dystrophin isoform Dp260.

PMID- 17503326
TI  - A mutation in CCDC50, a gene encoding an effector of epidermal growth factor
      mediated cell signaling, causes progressive hearing loss.
AB  - We previously mapped a novel autosomal dominant deafness locus, DFNA44, by
      studying a family with postlingual, progressive, nonsyndromic hearing loss. We
      report here on the identification of a mutation in CCDC50 as the cause of hearing
      loss in the family. CCDC50 encodes Ymer, an effector of epidermal growth factor
      (EGF)-mediated cell signaling that is ubiquitously expressed in different organs
      and has been suggested to inhibit down-regulation of the EGF receptor. We have
      examined its expression pattern in mouse inner ear. Western blotting and cell
      transfection results indicate that Ymer is a soluble, cytoplasmic protein, and
      immunostaining shows that Ymer is expressed in a complex spatiotemporal pattern
      during inner ear development. In adult inner ear, the expression of Ymer is
      restricted to the pillar cells of the cochlea, the stria vascularis, and the
      vestibular sensory epithelia, where it shows spatial overlap with the microtubule
      based cytoskeleton. In dividing cells, Ymer colocalizes with microtubules of the
      mitotic apparatus. We suggest that DFNA44 hearing loss may result from a time
      dependent disorganization of the microtubule-based cytoskeleton in the pillar
      cells and stria vascularis of the adult auditory system.

PMID- 17503327
TI  - Homozygosity haplotype allows a genomewide search for the autosomal segments
      shared among patients.
AB  - A promising strategy for identifying disease susceptibility genes for both single
      and multiple-gene diseases is to search patients' autosomes for shared
      chromosomal segments derived from a common ancestor. Such segments are
      characterized by the distinct identity of their haplotype. The methods and
      algorithms currently available have only a limited capability for determining a
      high-resolution haplotype genomewide. We herein introduce the homozygosity
      haplotype (HH), a haplotype described by the homozygous SNPs that are easily
      obtained from high-density SNP genotyping data. The HH represents haplotypes of
      both copies of homologous autosomes, allowing for direct comparisons of the
      autosomes among multiple patients and enabling the identification of the shared
      segments. The HH successfully detected the shared segments from members of a
      large family with Marfan syndrome, which is an autosomal dominant, single-gene
      disease. It also detected the shared segments from patients with model multigene
      diseases originating with common ancestors who lived 10-25 generations ago. The
      HH is therefore considered to be useful for the identification of disease
      susceptibility genes in both single- and multiple-gene diseases.

PMID- 17503328
TI  - IRAK-M is involved in the pathogenesis of early-onset persistent asthma.
AB  - Asthma is a multifactorial disease influenced by genetic and environmental
      factors. In the past decade, several loci and >100 genes have been found to be
      associated with the disease in at least one population. Among these loci, region
      12q13-24 has been implicated in asthma etiology in multiple populations,
      suggesting that it harbors one or more asthma susceptibility genes. We performed
      linkage and association analyses by transmission/disequilibrium test and case
      control analysis in the candidate region 12q13-24, using the Sardinian founder
      population, in which limited heterogeneity of pathogenetic alleles for monogenic
      and complex disorders as well as of environmental conditions should facilitate
      the study of multifactorial traits. We analyzed our cohort, using a cutoff age of
      13 years at asthma onset, and detected significant linkage to a portion of 12q13
      24. We identified IRAK-M as the gene contributing to the linkage and showed that
      it is associated with early-onset persistent asthma. We defined protective and
      predisposing SNP haplotypes and replicated associations in an outbred Italian
      population. Sequence analysis in patients found mutations, including inactivating
      lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies
      showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M
      is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a
      negative regulator of the Toll-like receptor/IL-1R pathways, is a master
      regulator of NF- kappa B and inflammation. Our data suggest a mechanistic link
      between hyperactivation of the innate immune system and chronic airway
      inflammation and indicate IRAK-M as a potential target for therapeutic
      intervention against asthma.

PMID- 17503329
TI  - A common haplotype in the G-protein-coupled receptor gene GPR74 is associated
      with leanness and increased lipolysis.
AB  - The G-protein-coupled receptor GPR74 is a novel candidate gene for body weight
      regulation. In humans, it is predominantly expressed in brain, heart, and adipose
      tissue. We report a haplotype in the GPR74 gene, ATAG, with allele frequency ~4%
      in Scandinavian cohorts, which was associated with protection against obesity in
      two samples selected for obese and lean phenotypes (odds ratio for obesity 0.48
      and 0.62; nominal P=.0014 and .014; n=1,013 and 1,423, respectively). In a
      population-based sample, it was associated with lower waist (P=.02) among 3,937
      men and with obesity protection (odds ratio 0.36; P=.036) among those selected
      for obese or lean phenotypes. The ATAG haplotype was associated with increased
      adipocyte lipid mobilization (lipolysis) in vivo and in vitro. In human fat
      cells, GPR74 receptor stimulation and inhibition caused a significant and marked
      decrease and increase, respectively, of lipolysis, which could be linked to
      catecholamine stimulation of adipocytes through beta -adrenergic receptors. These
      findings suggest that a common haplotype in the GPR74 gene protects against
      obesity, which, at least in part, is caused by a relief of inhibition of lipid
      mobilization from adipose tissue. The latter involves a cross-talk between GPR74
      and beta -adrenoceptor signaling to lipolysis in fat cells.

PMID- 17503330
TI  - A generalized combinatorial approach for detecting gene-by-gene and gene-by
      environment interactions with application to nicotine dependence.
AB  - The determination of gene-by-gene and gene-by-environment interactions has long
      been one of the greatest challenges in genetics. The traditional methods are
      typically inadequate because of the problem referred to as the "curse of
      dimensionality." Recent combinatorial approaches, such as the multifactor
      dimensionality reduction (MDR) method, the combinatorial partitioning method, and
      the restricted partition method, have a straightforward correspondence to the
      concept of the phenotypic landscape that unifies biological, statistical
      genetics, and evolutionary theories. However, the existing approaches have
      several limitations, such as not allowing for covariates, that restrict their
      practical use. In this study, we report a generalized MDR (GMDR) method that
      permits adjustment for discrete and quantitative covariates and is applicable to
      both dichotomous and continuous phenotypes in various population-based study
      designs. Computer simulations indicated that the GMDR method has superior
      performance in its ability to identify epistatic loci, compared with current
      methods in the literature. We applied our proposed method to a genetics study of
      four genes that were reported to be associated with nicotine dependence and found
      significant joint action between CHRNB4 and NTRK2. Moreover, our example
      illustrates that the newly proposed GMDR approach can increase prediction
      ability, suggesting that its use is justified in practice. In summary, GMDR
      serves the purpose of identifying contributors to population variation better
      than do the other existing methods.

PMID- 17503331
TI  - Defining the cause of skewed X-chromosome inactivation in X-linked mental
      retardation by use of a mouse model.
AB  - Extreme skewing of X-chromosome inactivation (XCI) is rare in the normal female
      population but is observed frequently in carriers of some X-linked mutations.
      Recently, it has been shown that various forms of X-linked mental retardation
      (XLMR) have a strong association with skewed XCI in female carriers, but the
      mechanisms underlying this skewing are unknown. ATR-X syndrome, caused by
      mutations in a ubiquitously expressed, chromatin-associated protein, provides a
      clear example of XLMR in which phenotypically normal female carriers virtually
      all have highly skewed XCI biased against the X chromosome that harbors the
      mutant allele. Here, we have used a mouse model to understand the processes
      causing skewed XCI. In female mice heterozygous for a null Atrx allele, we found
      that XCI is balanced early in embryogenesis but becomes skewed over the course of
      development, because of selection favoring cells expressing the wild-type Atrx
      allele. Unexpectedly, selection does not appear to be the result of general
      cellular-viability defects in Atrx-deficient cells, since it is restricted to
      specific stages of development and is not ongoing throughout the life of the
      animal. Instead, there is evidence that selection results from independent tissue
      specific effects. This illustrates an important mechanism by which skewed XCI may
      occur in carriers of XLMR and provides insight into the normal role of ATRX in
      regulating cell fate.

PMID- 17503332
TI  - Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053
      individuals.
AB  - The role of genes in normal birth-weight variation is poorly understood, and it
      has been suggested that the genetic component of fetal growth is small. Type 2
      diabetes genes may influence birth weight through maternal genotype, by
      increasing maternal glycemia in pregnancy, or through fetal genotype, by altering
      fetal insulin secretion. We aimed to assess the role of the recently described
      type 2 diabetes gene TCF7L2 in birth weight. We genotyped the polymorphism
      rs7903146 in 15,709 individuals whose birth weight was available from six studies
      and in 8,344 mothers from three studies. Each fetal copy of the predisposing
      allele was associated with an 18-g (95% confidence interval [CI] 7-29 g) increase
      in birth weight (P=.001) and each maternal copy with a 30-g (95% CI 15-45 g)
      increase in offspring birth weight (P=2.8x10-5). Stratification by fetal genotype
      suggested that the association was driven by maternal genotype (31-g [95% CI 9-48
      g] increase per allele; corrected P=.003). Analysis of diabetes-related traits in
      10,314 nondiabetic individuals suggested the most likely mechanism is that the
      risk allele reduces maternal insulin secretion (disposition index reduced by
      ~0.15 standard deviation; P=1x10-4), which results in increased maternal glycemia
      in pregnancy and hence increased offspring birth weight. We combined information
      with the other common variant known to alter fetal growth, the -30G-->A
      polymorphism of glucokinase (rs1799884). The 4% of offspring born to mothers
      carrying three or four risk alleles were 119 g (95% CI 62-172 g) heavier than
      were the 32% born to mothers with none (for overall trend, P=2x10-7), comparable
      to the impact of maternal smoking during pregnancy. In conclusion, we have
      identified the first type 2 diabetes-susceptibility allele to be reproducibly
      associated with birth weight. Common gene variants can substantially influence
      normal birth-weight variation.

PMID- 17503333
TI  - RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog
      signaling in cranial-suture development and obesity.
AB  - Carpenter syndrome is a pleiotropic disorder with autosomal recessive
      inheritance, the cardinal features of which include craniosynostosis,
      polysyndactyly, obesity, and cardiac defects. Using homozygosity mapping, we
      found linkage to chromosome 6p12.1-q12 and, in 15 independent families,
      identified five different mutations (four truncating and one missense) in RAB23,
      which encodes a member of the RAB guanosine triphosphatase (GTPase) family of
      vesicle transport proteins and acts as a negative regulator of hedgehog (HH)
      signaling. In 10 patients, the disease was caused by homozygosity for the same
      nonsense mutation, L145X, that resides on a common haplotype, indicative of a
      founder effect in patients of northern European descent. Surprisingly, nonsense
      mutations of Rab23 in open brain mice cause recessive embryonic lethality with
      neural-tube defects, suggesting a species difference in the requirement for RAB23
      during early development. The discovery of RAB23 mutations in patients with
      Carpenter syndrome implicates HH signaling in cranial-suture biogenesis--an
      unexpected finding, given that craniosynostosis is not usually associated with
      mutations of other HH-pathway components--and provides a new molecular target for
      studies of obesity.

PMID- 17503334
TI  - A genomewide admixture mapping panel for Hispanic/Latino populations.
AB  - Admixture mapping (AM) is a promising method for the identification of genetic
      risk factors for complex traits and diseases showing prevalence differences among
      populations. Efficient application of this method requires the use of a
      genomewide panel of ancestry-informative markers (AIMs) to infer the population
      of origin of chromosomal regions in admixed individuals. Genomewide AM panels
      with markers showing high frequency differences between West African and European
      populations are already available for disease-gene discovery in African
      Americans. However, no such a map is yet available for Hispanic/Latino
      populations, which are the result of two-way admixture between Native American
      and European populations or of three-way admixture of Native American, European,
      and West African populations. Here, we report a genomewide AM panel with 2,120
      AIMs showing high frequency differences between Native American and European
      populations. The average intermarker genetic distance is ~1.7 cM. The panel was
      identified by genotyping, with the Affymetrix GeneChip Human Mapping 500K array,
      a population sample with European ancestry, a Mesoamerican sample comprising Maya
      and Nahua from Mexico, and a South American sample comprising Aymara/Quechua from
      Bolivia and Quechua from Peru. The main criteria for marker selection were both
      high information content for Native American/European ancestry (measured as the
      standardized variance of the allele frequencies, also known as "f value") and
      small frequency differences between the Mesoamerican and South American samples.
      This genomewide AM panel will make it possible to apply AM approaches in many
      admixed populations throughout the Americas.

PMID- 17503336
TI  - Intragenic Cis and Trans modification of genetic susceptibility in DYT1 torsion
      dystonia.
AB  - A GAG deletion in the DYT1 gene is a major cause of early-onset dystonia, but
      clinical disease expression occurs in only 30% of mutation carriers. To gain
      insight into genetic factors that may influence penetrance, we evaluated three
      DYT1 single-nucleotide polymorphisms, including D216H, a coding-sequence
      variation that moderates the effects of the DYT1 GAG deletion in cellular models.
      We tested DYT1 GAG-deletion carriers with (n=119) and without (n=113) clinical
      signs of dystonia and control individuals (n=197) and found the frequency of the
      216H allele to be increased in GAG-deletion carriers without dystonia and to be
      decreased in carriers with dystonia, compared with the control individuals.
      Analysis of haplotypes demonstrated a highly protective effect of the H allele in
      trans with the GAG deletion; there was also suggestive evidence that the D216
      allele in cis is required for the disease to be penetrant. Our findings
      establish, for the first time, a clinically relevant gene modifier of DYT1.

PMID- 17503338
TI  - ASHG Board emphasizes communication and involvement.

PMID- 17503335
TI  - Matthew-Wood syndrome is caused by truncating mutations in the retinol-binding
      protein receptor gene STRA6.
AB  - Retinoic acid (RA) is a potent teratogen in all vertebrates when tight
      homeostatic controls on its endogenous dose, location, or timing are perturbed
      during early embryogenesis. STRA6 encodes an integral cell-membrane protein that
      favors RA uptake from soluble retinol-binding protein; its transcription is
      directly regulated by RA levels. Molecular analysis of STRA6 was undertaken in
      two human fetuses from consanguineous families we previously described with
      Matthew-Wood syndrome in a context of severe microphthalmia, pulmonary agenesis,
      bilateral diaphragmatic eventration, duodenal stenosis, pancreatic malformations,
      and intrauterine growth retardation. The fetuses had either a homozygous
      insertion/deletion in exon 2 or a homozygous insertion in exon 7 predicting a
      premature stop codon in STRA6 transcripts. Five other fetuses presenting at least
      one of the two major signs of clinical anophthalmia or pulmonary hypoplasia with
      at least one of the two associated signs of diaphragmatic closure defect or
      cardiopathy had no STRA6 mutations. These findings suggest a molecular basis for
      the prenatal manifestations of Matthew-Wood syndrome and suggest that phenotypic
      overlap with other associations may be due to genetic heterogeneity of elements
      common to the RA- and fibroblast growth factor-signaling cascades.

PMID- 17503339
TI  - Lymphatic and blood vessel morphometry in invasive breast carcinomas: relation
      with proliferation and VEGF-C and -D proteins expression.
AB  - INTRODUCTION: The aim of the present study was to investigate the distribution of
      both lymphatics and blood microvessels in invasive breast carcinomas and the
      clinicopathological and prognostic significance of their density and size related
      parameters as well as their correlation with the proliferative potential of the
      tumor and VEGF-C and -D expression. METHODS: Both single and double
      immunohistochemistry were applied on a series of 146 paraffin-embedded breast
      tissue specimens to detect VEGF-C and -D as well as lymphatics and blood
      microvessels, respectively. Computer-assisted morphometry was performed to
      evaluate the blood and lymphatic vessel density (BVD and LVD respectively) as
      well as various vascular size related parameters. RESULTS: Lymphatics were
      detected within the stroma at the tumor border, while blood vessels were located
      in both the interior of the tumor mass and peritumor stroma. BV major axis, minor
      axis and perimeter inversely correlated with ER (p=0.011, p=0.023 and p=0.008
      respectively), while LV major axis, minor axis and the perimeter inversely
      correlated with tumor nuclear grade (p=0.045, p=0.037 and p=0.032 respectively)
      and topoisomerase IIalpha (p=0.015, p=0.024 and p=0.045 respectively). The same
      LV parameters were found to positively correlate with cancerous VEGF-C (p<0.0001,
      p=0.092 and p=0.012 respectively) and VEGF-D in the stromal fibroblasts
      surrounding neoplastic cells (p=0.011, p=0.041 and p=0.026 respectively). High
      BVD exerted an unfavorable impact on both disease-free (p=0.021) and overall
      survival (p=0.031) of the patients. High LVD correlated with poor disease-free
      and overall survival only in the subgroup of patients with ER-negative tumors
      (p=0.056 and p=0.0312 respectively). CONCLUSION: These findings, for the first
      time, correlate lymphatic size with tumors of limited proliferative potential and
      higher nuclear differentiation. Moreover, they suggest that VEGF-C and -D
      expression influence lymphatic size rather than being involved in the increase of
      lymphatic vessel number.

PMID- 17503340
TI  - Cell proliferation and apoptosis in stromal corneal dystrophies.
AB  - The aim of our study was to evaluate corneal cell proliferation and apoptosis in
      cases of granular, macular and lattice dystrophy, and to provide evidence which
      may help to clarify whether apoptosis is a pathogenic factor in any of these
      dystrophies. The study group comprised 39 eyes (from 33 patients) which had
      undergone penetrating keratoplasty (PK) for stromal dystrophies: these comprised
      12 eyes (from 9 patients, 55.5% males) with granular dystrophy, 13 eyes (12
      patients, 33.3% males) with macular dystrophy, and 14 eyes (13 patients, 61.5%
      males) with lattice type I dystrophy. A further 4 corneal buttons from enucleated
      eyes of 4 patients with choroideal melanoma served as controls.
      Immunocytochemical analysis of Ki67 (DNAcon Kit, DakoCytomation A/S, Glostrup,
      Denmark) was used for evaluation of cell proliferation. Apoptosis was detected by
      use of the TUNEL (terminal deoxyribonucleotidyl transferase-mediated dUTP
      digoxigenin nick-end labelling) assay method (Apoptag reagent, Q-Biogene,
      Strasbourg, France). Statistical comparisons were made using the Mann-Whitney
      test. No Ki67-positive cells were detected in the study-group or control corneas.
      In control corneas no apoptotic activity was found. In the study group the mean
      (normalised) apoptotic keratocyte number was 1.1+/-1.7 in granular dystrophy and
      0.5+/-1.1 in lattice type I dystrophy (p = 0.36, 0.63 respectively). Compared to
      the controls, the difference was statistically significant only for macular
      dystrophy (1.6+/-1.2; p = 0.01). Keratocyte apoptosis seems to be a concomitant
      or pathogenic factor in macular dystrophy. However, the pathways that are
      triggered to result in increased apoptotic cell death remain to be clarified.

PMID- 17503341
TI  - Expression of Toll-like receptors in the human decidua.
AB  - BACKGROUND: Successful trophoblast invasion and transformation of the maternal
      spiral arteries requires that the pregnant endometrium (i.e., decidua) act in an
      immunologically paradoxical fashion, accepting the semi-allogenic placenta, while
      maintaining host defenses against an array of microbial pathogens. In contrast to
      the growing evidence that the immune surveillance molecules known as Toll-like
      receptors (TLRs) are expressed by trophoblasts and fetal membranes, to date, no
      studies have been conducted on the decidua. METHODS: Decidual tissues and cells
      were obtained from women undergoing first trimester elective terminations or
      repeat Cesarean sections and analyzed at both the protein and mRNA level.
      RESULTS: We now demonstrate for the first time that human decidua differentially
      express TLRs and their downstream signaling molecules as well as TLR stimulated
      induction of cytokine production in the first and third trimester of pregnancy.
      CONCLUSIONS: These findings suggest that the decidua is a critical component of
      the innate immune response in pregnancy. Moreover, the results have implications
      for the success or failure of compromised pregnancies in early or late gestation.

PMID- 17503342
TI  - Aging in the vestibular nuclear complex of the male golden hamster (Mesocricetus
      auratus): anatomic and morphometric study.
AB  - To study the effects of senescence on the vestibular nuclear complex twenty
      brainstems from male golden hamsters between 3 and 27 months-old were used and
      the possible variations in the number of neurons, neuronal morphology and nuclear
      volume were studied. The neuron profiles were drawn with a camera lucida and
      Abercrombie's method was used to estimate the total number of neurons. The test
      of Kolmogorov-Smirnov with the correction of Lilliefors was used to evaluate the
      fit of our data to a normal distribution and a regression analysis was done to
      decide if the variation of our data with age was statistically significant. The
      results of the present study are relevant only for male animals and the effect of
      senescence could be different in female vestibular nuclear complex. Aging affects
      the volume of the superior and lateral vestibular nuclei, as well as the nuclear
      neuronal diameter of the medial vestibular nucleus, but no significant neuronal
      loss has been appreciated in vestibular nuclear complex related with age. During
      the aging process we have observed that the distribution of neurons within the
      vestibular nuclei of the golden hamster does not show important changes and most
      of their morphometric parameters do not vary significantly.

PMID- 17503343
TI  - Lipid peroxidation was associated to the impairment of the fertilizing capability
      of gilthead sperm exposed to surfactants.
AB  - The present study was designed to determine whether lipid peroxidation was
      associated with the impairment of the fertilizing capability of gilthead sperm
      after acute exposure to anionic surfactant Sodium Dodecyl Sulphate (SDS). Spawned
      eggs and sperm were collected from adult giltheads. Sperm suspensions
      (100,000,000 spermatozoa/mL) were dosed separately with different concentrations
      of SDS (0.6, 1.5, 3 and 6 mg/L) for 60 minutes. After this period, sperm samples
      were randomly distributed for both outcome measurements: fertilization percentage
      or lipid peroxidation assessment. On one hand, exposed sperm and unexposed eggs
      were combined for 20 minutes during which fertilization took place.
      Fertilization, defined as the presence of a fertilization envelope, was assessed
      by microscopic observation. On the other hand lipid peroxidation on exposed
      gilthead sperm was determined by estimating the production of malondialdehyde
      (MDA). Acute exposure to SDS caused a significant inhibitory effect on
      fertilization success in gilthead. It also increased significantly lipid
      peroxidation in exposed sperm. Furthermore, a strong but negative statistical
      association was found between fertilizing capability and lipid peroxidation
      gilthead sperm exposed to SDS. Although extrapolation from the laboratory to the
      field requires caution, the results of this work demonstrated that the impairment
      of fertilization was significantly associated with lipid peroxidation induced by
      acute exposure to SDS. Consequently lipid peroxidation may be recommended as an
      early-warning bioindicator of exposure to surfactants. Further studies are
      required.

PMID- 17503344
TI  - Characterization of cell motility in single heart valve interstitial cells in
      vitro.
AB  - Valve interstitial cells (VIC) are the most prevalent cells in the heart valve,
      regulating to a large extent the normal biology of the valve and its
      pathobiological response to disease. In the process of valve tissue repair by
      VICs, single cell motility is likely to be important, as it is in wound repair by
      most mesenchymal type cells. We designed in vitro experiments using low density
      monolayer cultures to study the association of morphology and motility in single
      VICs which expressed alpha-smooth muscle actin. We observed that the morphology
      of single VICs can be categorized into six types which are reminiscent of the
      shape of VICs seen in vivo during valve repair. Of these morphologies, round,
      rhomboid, tailed and spindled shaped VICs were the most common. VICs did change
      their morphology over time. Rhomboid cells could become tailed or spindle-shaped
      and vice versa. Using time-lapse imaging and immunofluorescent microscopy, we
      showed that VIC morphologies reflect differences in cell motility and cell-matrix
      interactions. Tailed and spindle-shaped VICs were the predominant motile types
      and were associated with few extracellular fibronectin fibrils and less focal
      adhesions, as demonstrated by vinculin staining. Round and rhomboid shaped VICs
      were less motile and were associated with prominent vinculin and extracellular
      fibronectin fibrils. We found that cell mitosis is an important determinant of
      VIC migration. Many of the motile VICs were associated with mitosis as the
      daughter cells separated by migrating as tailed and spindle shaped cells. Thus
      cell morphology is an important determinant of VIC motility.

PMID- 17503345
TI  - Renal leiomyoma: an immunohistochemical, ultrastructural and comparative genomic
      hybridization study.
AB  - Renal leiomyoma is a rare neoplasm. We report such a case in a 57-year-old
      Japanese woman who was found to have a mass in the left kidney. The histological
      examination disclosed the proliferation of spindle cells showing a benign
      appearance. Entrapped tubular cells were observed in the peripheral area of the
      tumor. The immunohistochemical examination of spindle neoplastic cells showed a
      positive reaction for alpha smooth muscle actin, h-caldesmon, l-caldesmon,
      calponin, muscle actin, myosin and desmin. Additionally, the ultrastructural
      examination of the tumor showed membrane caveolae and myofilaments in the
      cytoplasm. This tumor was considered to show a differentiation into smooth muscle
      cells. The comparative genomic hybridization of the tumor detected the combined
      losses of chromosomes 4, 6, 12 and 14 which has not been previously described in
      renal tumors. Finally, the immunohistochemical panel of smooth muscle markers and
      ultrastructural and genetic study may be useful in diagnosing renal leiomyoma.

PMID- 17503346
TI  - MUC1 (EMA) expressing plasma cells in bone marrow infiltrated by plasma cell
      myeloma.
AB  - MUC1 (also called: epithelial membrane antigen, EMA) represents a mucin molecule
      strongly expressed in various epithelia and epithelial neoplasms. Its expression
      correlates with clinical and pathological factors as well as prognosis in some
      tumor types. Additionally, MUC1 was detected in normal haematopoietic cell lines
      and neoplasms, especially subgroups of human lymphomas including plasma cell
      myeloma. Therefore, the expression of MUC1 in trephine biopsies exhibiting
      infiltrates of plasma cell myeloma were investigated immunohistochemically. An
      immunoreactivity of two monoclonal antibodies (EMA and HMFG-2) was observed in
      about 50% of the cases. In cases exhibiting a so-called packed marrow, EMA
      immunoreactivity was reduced. However, MUC1 positivity did not correlate with the
      cytologic grade of differentiation, the fibre content of the marrow, or survival
      probability of the patients. However, its strong expression in a certain
      percentage of cases of plasma cell myeloma may be of therapeutic impact, since
      new therapeutic strategies include the enrichment of MUC1-specific T cells or
      MUC1 vaccination.

PMID- 17503347
TI  - Mammalian target of rapamycin: master regulator of cell growth in the nervous
      system.
AB  - The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine
      protein kinase that regulates a number of diverse biologic processes important
      for cell growth and proliferation, including ribosomal biogenesis and protein
      translation. In this regard, hyperactivation of the mTOR signaling pathway has
      been demonstrated in numerous human cancers, including a number of inherited
      cancer syndromes in which individuals have an increased risk of developing benign
      and malignant tumors. Three of these inherited cancer syndromes (Lhermitte-Duclos
      disease, neurofibromatosis type 1, and tuberous sclerosis complex) are
      characterized by significant central nervous system dysfunction and brain tumor
      formation. Each of these disorders is caused by a genetic mutation that disrupts
      the expression of proteins which negatively regulate mTOR signaling, indicating
      that the mTOR signaling pathway is critical for appropriate brain development and
      function. In this review, we discuss our current understanding of the mTOR
      signaling pathway and its role in promoting ribosome biogenesis and cell growth.
      We suggest that studies of this pathway may prove useful in identifying molecular
      targets for biologically-based therapies of brain tumors associated with these
      inherited cancer syndromes as well as sporadic central nervous system tumors.

PMID- 17503348
TI  - Advances of MUC1 as a target for breast cancer immunotherapy.
AB  - MUC1 is a potential target in breast cancer immunotherapy as MUC1 is
      overexpressed in breast cancer, and is absent or expressed in low level in normal
      mammary gland. In addition, MUC1 is mostly aberrantly underglycosylated in cancer
      and the antigens on the cancer surface are different from normal cell. Therefore
      targeting MUC1 for cancer immunotherapy can exploit the difference between cancer
      and normal cells, and eliminating the cancerous cells while leaving the normal
      mammary cells unharmed. This review will focus on the recent advance of MUC1
      breast cancer immunotherapy currently being investigated.

PMID- 17503349
TI  - Diagnosis of Hodgkin's disease: an update on histopathological and
      immunophenotypical features.
AB  - The Hodgkin lymphoma (HL) is a B-cell lymphoma, as was proved by molecular
      studies with single-cell PCR. Histologically, it is characterized by a minority
      of neoplastic cells, Reed-Sternberg cells and its variants, related to a variable
      non-neoplastic inflammatory background. Nowadays, (WHO classification) the
      following types of HL are recognized: Nodular Paragranuloma and the Classical
      Hodgkin Lymphoma, the latter including Nodular Sclerosis, Mixed Cellularity,
      Lymphocyte-rich Classical Hodgkin Lymphoma and Lymphocyte Depletion. Morphology
      together with immunohistochemical studies allows to classify the different forms
      of Hodgkin lymphoma and to make a differential diagnosis with non-Hodgkin
      lymphomas. All classical Hodgkin lymphomas are treated similarly, and chances for
      remission and survival are currently good. Molecular parameters should be added
      to the current classification and patients could benefit from new therapeutic
      targets.

PMID- 17503350
TI  - New insights into the cytoplasmic function of PML.
AB  - PML is a tumour suppressor inactivated in Acute Promyelocytic Leukaemia (APL).
      PML is the essential component of a subnuclear structure called the PML nuclear
      body (PML-NB), which is disrupted in APL. By targeting different cellular
      proteins to this structure, PML can either hamper or potentiate their functions.
      The PML transcript undergoes alternative splicing to generate both nuclear and
      cytoplasmic isoforms. Most of the research in this field has focused its
      attention on studying nuclear PML. Nevertheless, new exciting studies show that
      cytoplasmic PML may control essential cellular functions, thus opening new
      avenues for investigation.

PMID- 17503351
TI  - Multiple methods for protein side chain packing using maximum weight cliques.
AB  - In this paper, we present several methods for computing a solution to the protein
      side chain packing problem, with all methods having a common solution approach of
      breaking the polymer into subpolymers and using maximum edge weight cliques to
      prune the search space for the optimal side chain packing. We characterize the
      graph sizes generated for each method and compare their prediction accuracies.
      These methods are demonstrated for computing proteins up to approximately 8000
      residues. In addition, we update a result published previously.

PMID- 17503352
TI  - Computational methods for functional site identification suggest a substrate
      access channel in transaldolase.
AB  - The homozygous deletion of Serine 171 results in the catalytic inactivation of
      the human transaldolase. Since Ser171 is in an outside loop, whereas the
      catalytic site is inside of the alpha/beta-barrel of the protein at least 15 A
      away, the loss of activity is difficult to explain. Two distinct computational
      methods are used to elucidate the potential origin of inactivation. Computational
      solvent mapping, which moves small organic molecules as probes around a protein
      surface and finds favorable binding positions, identifies the region around
      Ser171 as an important binding site. Three-dimensional cluster analysis, based
      both on a reference structure and multiple sequence alignment, shows that a patch
      of functionally important residues extends from Ser171 toward the catalytic site.
      Based on the findings of these two methods, we propose a novel ligand access path
      connecting these specific sites to the enzyme's active site. We also suggest that
      this mechanism may be aided by a significant conformational change involving the
      separation of two helices, alphaD and alphaG, in order to create an easy-access
      channel between the Ser171-related site and the active site. Further experimental
      procedures will be necessary to examine the biological feasibility of this
      proposed ligand shuttling path.

PMID- 17503353
TI  - Inferring protein-protein interactions in viral proteins by co-evolution of
      conserved side chains.
AB  - We introduce a new and potentially valuable method for delineating the repertoire
      of protein complexes in highly mutable organisms and, in conjunction with other
      methods, for specifying the structural details of complexes. In the first
      instance the method provides a guide to selecting proteins for co
      crystallization; in the second it augments the collection of structures
      determined by crystallography and other methods, including the discovery of
      possible alternative binding sites of known complexes. The key to the method is
      the availability of multiple sequence variants of an organism-arrived at either
      naturally or by directed mutagenesis in appropriate laboratory facilities. Amino
      acids that are important for the structural stability of a protein or complex
      tend to be conserved, generally mutating only when compensatory changes occur.
      Consequently significant correlations in variation of two conserved amino acids
      in the same protein suggest that they interact with one another, either directly
      or indirectly. Similarly, correlated mutations between conserved amino acids in
      different proteins suggest that they may be at a site of physical interaction. We
      have identified all highly conserved 9-11 amino acid long segments from HIV
      proteins and then identified pairs from different proteins with highly
      significant co-variation. Using the HIV reverse transcriptase and integrase
      proteins as an example, we demonstrate how the interface and combining sites can
      be inferred by co-variation analysis and rigid body docking. The potential
      significance for antiviral drug and vaccine design is briefly discussed.

PMID- 17503354
TI  - Systematic functional assessment of human protein-protein interaction maps.
AB  - Protein-protein interaction maps can contribute substantially to the discovery of
      protein cooperation patterns in the cell. Recently, several large-scale human
      protein-protein interaction maps have been generated using experimental or
      computational approaches. Evaluation of these maps is likely to provide a better
      understanding of human biology. However, careful analysis is needed, as the
      comparison of interaction maps of lower eukaryotes showed a surprising divergence
      between different maps. Here, we present a first systematic functional assessment
      of eight currently available large-scale human protein-protein interaction maps.
      The analysis shows that these maps include a large number of common proteins, but
      only a small number of common interactions. We detected several types of biases
      that need to be considered in the future utilization of these maps.

PMID- 17503355
TI  - Genomic data assimilation for estimating hybrid functional Petri net from time
      course gene expression data.
AB  - We propose an automatic construction method of the hybrid functional Petri net as
      a simulation model of biological pathways. The problems we consider are how we
      choose the values of parameters and how we set the network structure. Usually, we
      tune these unknown factors empirically so that the simulation results are
      consistent with biological knowledge. Obviously, this approach has the limitation
      in the size of network of interest. To extend the capability of the simulation
      model, we propose the use of data assimilation approach that was originally
      established in the field of geophysical simulation science. We provide genomic
      data assimilation framework that establishes a link between our simulation model
      and observed data like microarray gene expression data by using a nonlinear state
      space model. A key idea of our genomic data assimilation is that the unknown
      parameters in simulation model are converted as the parameter of the state space
      model and the estimates are obtained as the maximum a posteriori estimators. In
      the parameter estimation process, the simulation model is used to generate the
      system model in the state space model. Such a formulation enables us to handle
      both the model construction and the parameter tuning within a framework of the
      Bayesian statistical inferences. In particular, the Bayesian approach provides us
      a way of controlling overfitting during the parameter estimations that is
      essential for constructing a reliable biological pathway. We demonstrate the
      effectiveness of our approach using synthetic data. As a result, parameter
      estimation using genomic data assimilation works very well and the network
      structure is suitably selected.

PMID- 17503356
TI  - SBMLmerge, a system for combining biochemical network models.
AB  - The Systems Biology Markup Language (SBML) is an XML-based format for
      representing mathematical models of biochemical reaction networks, and it is
      likely to become a main standard in the systems biology community. As published
      mathematical models in cell biology are growing in number and size, modular
      modelling approaches will gain additional importance. The main issue to be
      addressed in computer-assisted model combination is the specification and
      handling of model semantics. The software SBMLmerge assists the user in combining
      models of biological subsystems to larger biochemical networks. First, the
      program helps the user in annotating all model elements with unique identifiers
      pointing to databases such as KEGG or Gene Ontology. Second, during merging,
      SBMLmerge detects and resolves various syntactic and semantic problems. Typical
      problems are conflicting variable names, elements which appear in more than one
      input model, and mathematical problems arising from the combination of equations.
      If the input models make contradicting statements about a biochemical quantity,
      the user is asked to choose between them. In the end the merging process results
      in a new, valid SBML model.

PMID- 17503357
TI  - Why do cells cycle with a 24 hour period?
AB  - A typical proliferating human cell divides on average every 24 h. This division
      timing allows cells to synchronize with other physiological processes and with
      the environment. The circadian clock, which orchestrates daily rhythms, directly
      regulates the cell division cycle and is a major synchronizing factor. There is,
      however, no evidence that the circadian clock is able to entrain the cell cycle
      to a 24 h period. We show here, using a computational model for the cell cycle,
      that cells under circadian control that have an interdivision time close to
      multiples of 24 h proliferate faster. Moreover, growth of cell populations with a
      markedly different cell cycle time is impaired. We propose that this resonance
      effect in cell proliferation has a role to play in efficient normal cell
      proliferation and suppression of tumor growth.

PMID- 17503358
TI  - Prediction of enzyme kinetic parameters based on statistical learning.
AB  - Values of enzyme kinetic parameters are a key requisite for the kinetic modelling
      of biochemical systems. For most kinetic parameters, however, not even an order
      of magnitude is known, so the estimation of model parameters from experimental
      data remains a major task in systems biology. We propose a statistical approach
      to infer values for kinetic parameters across species and enzymes making use of
      parameter values that have been measured under various conditions and that are
      nowadays stored in databases. We fit the data by a statistical regression model
      in which the substrate, the combination enzyme-substrate and the combination
      organism-substrate have a linear effect on the logarithmic parameter value. As a
      result, we obtain predictions and error ranges for unknown enzyme parameters. We
      apply our method to decadic logarithmic Michaelis-Menten constants from the
      BRENDA database and confirm the results with leave-one-out crossvalidation, in
      which we mask one value at a time and predict it from the remaining data. For a
      set of 8 metabolites we obtain a standard prediction error of 1.01 for the
      deviation of the predicted values from the true values, while the standard
      deviation of the experimental values is 1.16. The method is applicable to other
      types of kinetic parameters for which many experimental data are available.

PMID- 17503359
TI  - A statistical framework for genome-wide discovery of biomarker splice variations
      with GeneChip Human Exon 1.0 ST Arrays.
AB  - Alternative splicing is an important regulatory mechanism that generates multiple
      mRNA transcripts which are transcribed into functionally diverse proteins.
      According to the current studies, aberrant transcripts due to splicing mutations
      are known to cause for 15% of genetic diseases. Therefore understanding
      regulatory mechanism of alternative splicing is essential for identifying
      potential biomarkers for several types of human diseases. Most recently, advent
      of GeneChip Human Exon 1.0 ST Array enables us to measure genome-wide expression
      profiles of over one million exons. With this new microarray platform, analysis
      of functional gene expressions could be extended to detect not only
      differentially expressed genes, but also a set of specific-splicing events that
      are differentially observed between one or more experimental conditions, e.g.
      tumor or normal control cells. In this study, we address the statistical problems
      to identify differentially observed splicing variations from exon expression
      profiles. The proposed method is organized according to the following process:
      (1) Data preprocessing for removing systematic biases from the probe intensities.
      (2) Whole transcript analysis with the analysis of variance (ANOVA) to identify a
      set of loci that cause the alternative splicing-related to a certain disease. We
      test the proposed statistical approach on exon expression profiles of colorectal
      carcinoma. The applicability is verified and discussed in relation to the
      existing biological knowledge. This paper intends to highlight the potential role
      of statistical analysis of all exon microarray data. Our work is an important
      first step toward development of more advanced statistical technology.
      Supplementary information and materials are available from http://bonsai.ims.u
      tokyo.ac.jp/~yoshidar/IBSB2006_ExonArray.htm.

PMID- 17503360
TI  - Cell fate simulation model of gustatory neurons with MicroRNAs double-negative
      feedback loop by hybrid functional Petri net with extension.
AB  - Biological regulatory networks have been extensively researched. Recently, the
      microRNA regulation has been analyzed and its importance has increasingly
      emerged. We have applied the Hybrid Functional Petri net with extension (HFPNe)
      model and succeeded in creating model biological pathways, e.g. metabolic
      pathways, gene regulatory networks, cell signaling networks, and cell-cell
      interaction models with one of the HFPNe implementations Cell Illustrator. Thus,
      we have applied HFPNe to model regulatory networks that involve a new key
      regulator microRNA. As a test case, we selected the cell fate determination model
      of two gustatory neurons of Caenorhabditis elegans-ASE left (ASEL) and ASE right
      (ASER). These neurons are morphologically bilaterally symmetric but physically
      asymmetric in function. Johnston et al. have suggested that their cell fate is
      determined by the double-negative feedback loop involving the lsy-6 and mir-273
      microRNAs. Our simulation model confirms their hypothesis. In addition, other
      well-known mutants that are related with the double-negative feedback loop are
      also well-modeled. The new upstream regulator of lsy-6 (lsy-2) that is mentioned
      in another paper is also integrated into this model for the mechanism of
      switching between ASEL and ASER without any contradictions. Therefore, the HFPNe
      based modeling will be one of the promising modeling methods and simulation
      architectures that illustrate microRNA regulatory networks.

PMID- 17503361
TI  - A combined pathway to simulate CDK-dependent phosphorylation and ARF-dependent
      stabilization for p53 transcriptional activity.
AB  - The protein p53 is phosphorylated by a member of protein kinases such as CDK7,
      and stabilized by the protein ARF. The phosphorylation and stabilization of p53
      is believed to enhance its transcriptional activity and act simultaneously.
      Biological pathways composed of experts knowledge obtained from the literature
      are including these activation mechanisms. However, the map of biological
      pathways does not reflect the combination effect of phosphorylation and
      stabilization. We have conducted some simulations of biological pathways with
      hybrid functional Petri net (HFPN) after careful reading of papers. In this
      paper, we constructed the HFPN based biological pathway of CDK-dependent
      phosphorylation pathway and combine with ARF-dependent pathway described
      previously, to observe the effect of the phosphorylation on the stabilization
      with simulation-based validation.

PMID- 17503362
TI  - Systematic detection of statistically overrepresented DNA motif association
      rules.
AB  - DNA motifs, or cis-elements, are short nucleotide sequence patterns recognized by
      various transcription factors (TFs). In promoters, these TFs bind in a complex
      combinatorial manner in order to regulate the expression of a downstream gene.
      The combinatorial space is frequently large and difficult to manage since
      vertebrates have thousands of transcription factors and more than 20,000 genes.
      We introduce a computer program called CAYCE (Combinatorial AnalYsis of Cis
      Elements) that systematically detects statistically overrepresented DNA motif
      association rules independent of Microarray information. CAYCE is an adaptation
      of the apriori algorithm traditionally used for association rule mining, but
      offers three significant advancements. (1) It analyzes multiple occurrences of an
      item, corresponding to multiple TF binding sites, (2) It compares results with a
      biologically relevant background, and (3), it provides p-values for
      straightforward statistical interpretation. CAYCE can be easily applied to any
      item-set data where the investigator is also interested in multiple occurrences
      of a single item, and/or overrepresentation of association rules compared with a
      background. Applying CAYCE to human promoters in 1% of the human genome, we
      discover that motif clusters containing five repetitions of SP1 are the most
      statistically significant.

PMID- 17503364
TI  - Design and biological evaluation of photo-switchable inhibitors.
AB  - Photo-switchable compounds are becoming increasingly popular for a series of
      biological applications based on the reversible photo-control of structure and
      function of biomolecules. Three applications for the usage of BODTCM and
      hemithioindigo as photo-reactive compounds are described here. The structure of
      the villin headpiece was modified by replacing a part of the backbone with
      hemithioindigo, aiming at induction of the folding process by irradiation with a
      defined wavelength. The E-isomer of BODTCM was applied as potential inhibitor of
      the 12/15-lipoxygenase (12/15-LOX), which is implicated in the pathogenesis of
      inflammatory diseases. A required death domain for the binding of proapoptotic
      proteins (e.g. Bak) to the hydrophobic groove of antiapoptotic proteins is the
      BH3 helix. Inserting hemithioindigo into this short peptide, stabilization
      towards proteolytic degradation is achieved. Such photo-reactive compounds might
      be developed as potential drugs for a great variety of diseases.

PMID- 17503363
TI  - A new statistical model to select target sequences bound by transcription
      factors.
AB  - Transcription factors (TFs) play a key role in gene regulation by binding to
      target sequences. In silico prediction of potential binding to a sequence is a
      main task in computational biology. Although many methods have been proposed to
      tackle this problem, the statistical significance of the prediction is still not
      solved. We propose an approach to give a good approximation for the potential of
      a sequence to be bound by a TF. Instead of assessing distinct binding sites, we
      motivate to focus on the number of binding sites. Based on a suitable statistical
      model, probabilities for scoring are approximated for a TF to bind to a sequence.
      Two examples show the necessity of such a model as well as the superiority of the
      proposed method compared to standard approaches.

PMID- 17503365
TI  - Control of signal transduction cycles: general results and application to the Jak
      Stat pathway.
AB  - Signal transduction involves the transitions of proteins between inactive and
      active states that can be achieved by reversible phosphorylation, nucleo
      cytoplasmic transport, and other processes. We consider a network of such state
      transitions governed by first-order kinetics and analyse how the reactions
      control the occupancy of the network states. First, a theorem is derived that
      relates concentration control coefficients and occupancy of the network states.
      Second, it is shown that the absolute value of each control coefficient is
      bounded by unity, so that the network does not exhibit ultrasensitive responses.
      Third, the signs of certain control coefficients are derived from the network
      topology. These results are applied to a mathematical model of the Jak/Stat1
      signaling. This pathway has been thought to function as a continuous cycle of
      cytoplasmic activation, nuclear import, inactivation and re-export of Stat1
      transcription factors, but the recent discovery of an apparently futile nucleo
      cytoplasmic cycle of inactive Stat1 has yielded a more complex picture. We
      demonstrate here two consequences of shuttling: (1) homeostasis of
      unphosphorylated Stat1 in the cell nucleus and (2) enhanced stimulus sensitivity
      of the pathway, and discuss their functional implications.

PMID- 17503366
TI  - Structural analysis of expressed metabolic subnetworks.
AB  - Expression of metabolic enzymes increases the metabolic capabilities of the cell,
      but it also consumes resources, and the gene regulatory systems of cells have to
      handle this tradeoff. To study whether gene expression patterns reflect the
      varying metabolic needs of the cell, we translated gene expression profiles into
      sets of active biochemical reactions, which constitute the expressed metabolic
      subnetworks. The metabolic capacity of a carbon source denotes the number of
      metabolites that can be produced from this carbon source and some inorganic
      nutrients. We studied the metabolic subnetworks that are expressed during diauxic
      shift in yeast and found that the capacities of different carbon sources tend to
      decrease during the diauxic shift. The subnetwork expressed in the initial
      glucose environment shows a high capacity of glucose, much higher than networks
      of the same size arising in later stages of the diauxic shift or from a random
      selection of reactions. The same holds for the essential capacity, the number of
      important, constitutive compounds that can be produced from glucose. These
      findings indicate that gene regulation increases the range of essential compounds
      that can be obtained from the available nutrients, while minimising the number of
      expressed enzymes and therefore the burden of protein synthesis.

PMID- 17503367
TI  - The repertoire of desaturases for unsaturated fatty acid synthesis in 397
      genomes.
AB  - Fatty acids are the major components of membrane molecules. The fact that
      unsaturated fatty acids play multiple important roles, physically and
      biologically, means that the ratio of unsaturated to saturated fatty acids in the
      membrane needs to be strictly regulated to maintain cellular homeostasis. The
      most ubiquitous and widespread modification to fatty acids, which results in a
      great diversity of different structures, is the insertion of double bonds. Fatty
      acid desaturases directly introduce regioselective double bonds into fatty acids.
      A phylogenetic analysis of desaturases suggests that the sequences of these
      proteins include a highly conserved domain, which determines the differences in
      specificity and regioselectivity found in these enzymes. In this study, we
      performed a systematic analysis of fatty acid desaturases found in the genomic
      data of 397 organisms. We obtained a set of desaturases clustered by
      regioselectivity using a hierarchal clustering analysis.

PMID- 17503368
TI  - Metabolite antigens and pathway incompatibility.
AB  - Vgamma9Vdelta2 cells, which constitute a small portion of peripheral blood T
      cells (approximately 5%), are known to be the biggest subset of human gammadelta
      T-cells ( approximately 70%) in circulating blood. The Vgamma9Vdelta2 T-cells
      expressing Vgamma9Vdelta2 T-cell receptors have an ability to recognize non
      peptide antigens directly or indirectly, for example, phosphorylated metabolites
      referred to as phosphoantigens, synthesized aminobisphosphonates used for
      therapeutic purpose such as pamidronate, and alkylamines. These chemical
      compounds recognized by Vgamma9Vdelta2 T-cells are produced by many prokaryotic
      and eukaryotic organisms. Previous works show that the phosphoantigens recognized
      by Vgamma9Vdelta2 T-cells are found as the intermediates in the pathogens'
      pathway producing IPP. In this paper, we show that the other compounds recognized
      by Vgamma9Vdelta2 T-cells are found on the pathogens' biosynthetic pathways
      leading to production of shared compounds with human. In addition, many compounds
      having high structural similarity with alkylamine antigens are also found only in
      pathogen's biosynthetic pathways or produced only by non-human enzymes.

PMID- 17503369
TI  - Composition of metabolic flux distributions by functionally interpretable minimal
      flux modes (MinModes).
AB  - All cellular functions are ultimately linked to the metabolism which constitutes
      a highly branched network of thousands of enzyme-catalyzed chemical reactions and
      carrier-mediated transport processes. Depending on the prevailing functions (e.g.
      detoxification of a toxin or accumulation of biomass) the distribution of fluxes
      in the metabolic network may vary considerably. To better reveal and quantify
      this flux-function relationship we propose a novel computational approach which
      identifies distinct contributions--so called minimal flux modes (short: MinModes)
      -to a stationary flux distribution in the network. Each of these contributions is
      characterized by a single metabolic output. A MinMode is a minimal (according to
      a defined cost function) steady state flux distribution that enables the
      production of a single metabolite. We apply this concept to a metabolic network
      of Methylobacterium extorquens AM1 comprising of 95 reactions and 74 metabolites,
      17 of these metabolites entering the biomass of the bacterium and are thus
      considered as the metabolic output of the network. MinModes represent a
      manageable set of fundamental flux modes in the network having a clear
      physiological meaning and--although not representing a basis in strict
      mathematical sense - provide a satisfactory approximation of the overall flux
      distribution in cases tested so far.

PMID- 17503370
TI  - Patterns of interactions of reaction pairs in metabolic networks.
AB  - A large scale structural analysis of metabolic networks is presented focusing on
      neighbourhood relationships between individual reactions. We define two reactions
      to be neighbored if one of them provides the necessary set of substances for the
      other to proceed. A method is developed which allows determining all possible
      neighborhood relationships categorized as interaction patterns. These patterns
      differ in the types of participating reactions and in the way they share their
      reactants. The method is applied to a set of 4795 metabolic reactions contained
      in the KEGG database. We show that from the 1547 theoretically possible types of
      interactions 282 patterns are found in metabolism. More than 55% of all
      interactions occur between reactions with at most two reactants on one side. In
      these interactions only 25 different patterns play a role. We propose to use
      these neighborhood relationships as a concept of adjacency in large scale graph
      theoretical analyses of metabolism.

PMID- 17503371
TI  - A high percentage of introns in human genes were present early in animal
      evolution: evidence from the basal metazoan Nematostella vectensis.
AB  - Intronic sequences represent a large fraction of most eukaryotic genomes, and
      they are known to play a critical role in genome evolution. Based on the
      conserved location of introns, conserved sequence within introns, and direct
      experimental evidence, it is becoming increasingly clear that introns perform
      important functions such as modulating gene expression. Here, we demonstrate that
      the positions of 69% (862/1246) of human introns in 343 orthologous genes are
      conserved in the starlet sea anemone Nematostella vectensis, a phylogenetically
      basal animal (phylum Cnidaria; class Anthozoa). This degree of intron concordance
      greatly exceeds that between humans and three more closely related animals:
      fruitfly (14%), mosquito (13%) and nematode worm (19%). Surprisingly, the
      fruitfly and mosquito, two members of the order Diptera, share only 43% of intron
      locations, fewer than the percentage of cumulative introns shared between human
      and sea anemone (47%), despite sharing a much more recent common ancestor. Our
      analysis indicates (1) that early animal genomes were intron-rich, (2) that a
      large fraction of introns present within the human genome likely originated early
      in evolution, before the cnidarian-bilaterian split, at least 600 million years
      ago, and (3) that there has been a high degree of intron loss during the
      evolution of the protostome lineage leading to the fruitfly, mosquito, and
      nematode. These data also reinforce the conclusion that there are functional
      constraints on the placement of introns in eukaryotic genes.

PMID- 17503372
TI  - Analysis of the differences in metabolic network expansion between prokaryotes
      and eukaryotes.
AB  - Recent evidence points to the existence of scale-free properties in many
      biological networks. By topological analysis, several models including
      preferential attachment and hierarchical modules have been proposed to explain
      how these networks are organized. On the other hand, analyses using dynamics have
      suggested that gene expression and metabolic networks have been organized with
      the scale-free property by the other models such as "rich-travel-more" and "log
      normal dynamics." Because most of these approaches are based on comparative
      genomics of extant species, and did not consider evolutionary events such as
      horizontal gene transfer, gene loss and gene gain, we have analyzed transition of
      metabolic networks from the vertical point of view of evolution. First, to
      identify metabolic networks of common ancestors, we applied a parsimony algorithm
      for the enzymatic reaction set. Then by comparing the estimated metabolic
      networks among common ancestors, we investigated the transition of metabolic
      networks along the evolutionary process. As a result, we estimated enzymatic
      reaction contents of 227 common ancestors from 228 extant species, and found that
      links of several specific metabolites have frequently changed during the course
      of evolution.

PMID- 17503373
TI  - About the interrelation of evolutionary rate and protein age.
AB  - Evolutionary rate and gene age are interrelated when the age of a gene is
      assessed by the taxonomic distribution in the gene family. This is because
      homology detection by sequence comparison is depending on sequence similarity. We
      estimate family specific rates of protein evolution for orthologous families with
      representatives from man, fugu, fly, and worm. In fact, we observe that younger
      proteins tend to evolve faster than older ones. We estimate time points of
      duplication events that gave rise to novel protein functions and show that
      younger proteins were duplicated more recently than older ones.

PMID- 17503374
TI  - Hybrid Gibbs-sampling algorithm for challenging motif discovery: GibbsDST.
AB  - The difficulties of computational discovery of transcription factor binding sites
      (TFBS) are well represented by (l, d) planted motif challenge problems. Large d
      problems are difficult, particularly for profile-based motif discovery
      algorithms. Their local search in the profile space is apparently incompatible
      with subtle motifs and large mutational distances between the motif occurrences.
      Herein, an improved profile-based method called GibbsDST is described and tested
      on (15,4), (12,3), and (18,6) challenging problems. For the first time for a
      profile-based method, its performance in motif challenge problems is comparable
      to that of Random Projection. It is noteworthy that GibbsDST outperforms a
      pattern-based algorithm, WINNOWER, in some cases. Effectiveness of GibbsDST using
      a biological dataset as an example and its possible extension to more realistic
      evolution models are also introduced.

PMID- 17503375
TI  - Computational annotation of transcription factor binding sites in D. Melanogaster
      developmental genes.
AB  - Drosophila melanogaster is one of the most important organisms for studying the
      genetics of development. The precise regulation of genes during early development
      is enacted through the control of transcription. The control circuitry is
      hardwired in the genome as clusters of multiple transcription factor binding
      sites (TFBS) known as cis-regulatory modules (CRMs). A number of TFBS and CRMs
      have been experimentally annotated in the Drosophila genome. Currently about 661
      CRM sequences are known, of which 155 have been annotated with 778 TFBS. This
      work attempts computational annotation of TFBS in the remaining 506
      uncharacterized Drosophila CRMs. The difficulty of this task lies in the fact
      that experimental data is insufficient for constructing reliable positional
      weight matrices (PWM) to predict the TFBS. Thus a novel feature extraction and
      classification method for TFBS detection has been implemented in this work. The
      method achieves both high sensitivity and low false positive rate in cross
      validation studies. As a result of this work, a new database has been compiled
      which aggregates all the CRM and TFBS annotation information for Drosophila
      available to date, and appends new TFBS annotations.

PMID- 17503376
TI  - A gram distribution kernel applied to glycan classification and motif extraction.
AB  - We propose a novel general-purpose tree kernel and apply it to glycan structure
      analysis. Our kernel measures the similarity between two labeled trees by
      counting the number of common q-length substrings (tree q-grams) embedded in the
      trees for all possible lengths q. We apply our tree kernel using a support vector
      machine (SVM) to classification and specific feature extraction from glycan
      structure data. Our results show that our kernel outperforms the layered trimer
      kernel of Hizukuri et al. which is well tailored to glycan data while we do not
      adjust our kernel to glycan-specific properties. In addition, we extract specific
      features from various types of glycan data using our trained SVM. The results
      show that our kernel is more flexible and capable of finding a wider variety of
      substructures from glycan data.

PMID- 17503377
TI  - Discovering signal transduction networks using signaling domain-domain
      interactions.
AB  - The objective of this paper is twofold. One objective is to present a method of
      predicting signaling domain-domain interactions (signaling DDI) using inductive
      logic programming (ILP), and the other is to present a method of discovering
      signal transduction networks (STN) using signaling DDI. The research on
      computational methods for discovering signal transduction networks (STN) has
      received much attention because of the importance of STN to transmit inter- and
      intra-cellular signals. Unlike previous STN works functioning at the protein/gene
      levels, our STN method functions at the protein domain level, on signal domain
      interactions, which allows discovering more reliable and stable STN. We can
      mostly reconstruct the STN of yeast MAPK pathways from the inferred signaling
      domain interactions, with coverage of 85%. For the problem of prediction of
      signaling DDI, we have successfully constructed a database of more than twenty
      four thousand ground facts from five popular genomic and proteomic databases. We
      also showed the advantage of ILP in signaling DDI prediction from the constructed
      database, with high sensitivity (88%) and accuracy (83%). Studying yeast MAPK
      STN, we found some new signaling domain interactions that do not exist in the
      well-known InterDom database. Supplementary materials are now available from
      http://www.jaist.ac.jp/s0560205/STP_DDI/.

PMID- 17503378
TI  - Finding conserved and non-conserved reactions using a metabolic pathway alignment
      algorithm.
AB  - Using a metabolic pathway alignment method we developed, we studied highly
      conserved reactions in different groups of organisms and found out that
      biological functions vital for each of the groups are effectively expressed in
      the set of conserved reactions. We also studied the metabolic alignment of
      different strains of three bacteria and found out several non-conserved
      reactions. We suggest that these reactions could be either misannotations or
      reactions with a relevant but yet to be specified biological role, and should
      therefore be further investigated.

PMID- 17503379
TI  - A function-centric approach to the biological interpretation of microarray time
      series.
AB  - The interpretation of microarray experiments is commonly addressed by means a two
      step approach in which the relevant genes are firstly selected uniquely on the
      basis of their experimental values (ignoring their coordinate behaviors) and in a
      second step their functional properties are studied to hypothesize about the
      biological roles they are fulfilling in the cell. Recently, different methods
      (e.g. GSEA or FatiScan) have been proposed to study the coordinate behavior of
      blocks of functionally-related genes. These methods study the distribution of
      functional information across lists of genes ranked according their different
      experimental values in a static situation, such as the comparison between two
      classes (e.g. healthy controls versus diseased cases). Nevertheless there is no
      an equivalent way of studying a dynamic situation from a functional point of
      view. We present a method for the functional analysis of microarrays series in
      which the experiments display autocorrelation between successive points (e.g.
      time series, dose-response experiments, etc.) The method allows to recover the
      dynamics of the molecular roles fulfilled by the genes along the series which
      provides a novel approach to functional interpretation of such experiments. The
      method finds blocks of functionally-related genes which are significantly and
      coordinately over-expressed at different points of the series. This method draws
      inspiration from systems biology given that the analysis does not focus on
      individual properties of genes but on collective behaving blocks of functionally
      related genes. The FatiScan algorithm used in the method proposed is available
      at: http://fatiscan.bioinfo.cipf.es}, or within the Babelomics suite:
      http://www.babelomics.org. Additional material is available at:
      http://bioinfo.cipf.es/data/plasmodium.

PMID- 17503380
TI  - RaPiDS: an algorithm for rapid expression profile database search.
AB  - In this paper we present a fast algorithm and implementation for computing the
      Spearman rank correlation (SRC) between a query expression profile and each
      expression profile in a database of profiles. The algorithm is linear in the size
      of the profile database with a very small constant factor. It is designed to
      efficiently handle multiple profile platforms and missing values. We show that
      our specialized algorithm and C++ implementation can achieve an approximately 100
      fold speed-up over a reasonable baseline implementation using Perl hash tables.
      RaPiDS is designed for general similarity search rather than classification - but
      in order to attempt to classify the usefulness of SRC as a similarity measure we
      investigate the usefulness of this program as a classifier for classifying normal
      human cell types based on gene expression. Specifically we use the k nearest
      neighbor classifier with a t statistic derived from SRC as the similarity measure
      for profile pairs. We estimate the accuracy using a jackknife test on the
      microarray data with manually checked cell type annotation. Preliminary results
      suggest the measure is useful (64% accuracy on 1,685 profiles vs. the majority
      class classifier's 17.5%) for profiles measured under similar conditions (same
      laboratory and chip platform); but requires improvement when comparing profiles
      from different experimental series.

PMID- 17503381
TI  - Development of an approach for ab initio estimation of compound-induced liver
      injury based on global gene transcriptional profiles.
AB  - Toxicity is a major cause of failure in drug development. A toxicogenomic
      approach may provide a powerful tool for better assessing the potential toxicity
      of drug candidates. Several approaches have been reported for predicting
      hepatotoxicity based on reference compounds with well-studied toxicity
      mechanisms. We developed a new approach for assessing compound-induced liver
      injury without prior knowledge of a compound's mechanism of toxicity. Using
      samples from rodents treated with 49 known liver toxins and 10 compounds without
      known liver toxicity, we derived a hepatotoxicity score as a single quantitative
      measurement for assessing the degree of induced liver damage. Combining the
      sensitivity of the hepatotoxicity score and the power of a machine learning
      algorithm, we then built a model to predict compound-induced liver injury based
      on 212 expression profiles. As estimated in an independent data set of 54
      expression profiles, the built model predicted compound-induced liver damage with
      90.9% sensitivity and 88.4% specificity. Our findings illustrate the feasibility
      of ab initio estimation of liver toxicity based on transcriptional profiles.

PMID- 17503382
TI  - The distribution and deposition algorithm for multiple oligo nucleotide arrays.
AB  - As the scale of the microarray experiments increases, a single oligo nucleotide
      array is no longer large enough. Therefore, the use of multiple oligo arrays for
      one experiment becomes more important. The design and synthesis of multiple
      arrays to minimize the overall synthesis cost is an interesting and important
      problem. We formulate the multiple array synthesis problem (MASP) that deals with
      the distribution of the probes (or oligos) to different arrays, and then
      deposition of the probes onto each array. We propose a cost function to capture
      the synthesis cost and a performance ratio for analysis of the quality of
      multiple arrays produced by different algorithms. We propose a Distribution and
      Deposition Algorithm (DDA) for the solving the MASP. In this algorithm, the
      probes are first distributed onto multiple arrays according to their
      characteristics such as GC contents. Then the probes on each arrays are deposited
      using a good deposition algorithm. Two other algorithms were also proposed and
      used for comparison. Experiments show that our algorithm can effectively output
      short synthesis sequences for multiple arrays, and the algorithm is efficient.

PMID- 17503383
TI  - Detection and restoration of hybridization problems in affymetrix GeneChip data
      by parametric scanning.
AB  - Gene expression microarray data often include problems caused by uneven
      hybridization and dust contamination. Such problems should be removed prior to
      analysis to prevent degradation of analytical accuracy and false positive
      results. This paper presents a parameter-scanning algorithm to detect such
      defects on the basis of the character of data distributions. The cell data is
      thoroughly scanned using a window algorithm, and windows with an index value
      greater than a threshold are recognized as defects and removed from the array
      data. The index is found from the differences between the target and an ideal
      standard of hybridization obtained as a trimmed mean among experiments,
      representing the statistical center of differences in each section. The threshold
      is derived as a screening level designated by the operator, but has only limited
      effect on the effectiveness of data cancellation. The validity of the algorithm
      and the effects of data cancellation are tested using GeneChip data obtained from
      a series of experiments. The algorithm is demonstrated to greatly improve the
      reproducibility of measurements, and removes only a small number of faultless
      data.

PMID- 17503384
TI  - Gene ontology annotation by density and gravitation models.
AB  - Gene Ontology (GO) is developed to provide standard vocabularies of gene products
      in different databases. The process of annotating GO terms to genes requires
      curators to read through lengthy articles. Methods for speeding up or automating
      the annotation process are thus of great importance. We propose a GO annotation
      approach using full-text biomedical documents for directing more relevant papers
      to curators. This system explores word density and gravitation relationships
      between genes and GO terms. Different density and gravitation models are built
      and several evaluation criteria are employed to assess the effects of the
      proposed methods.

PMID- 17503385
TI  - Text mining and protein annotations: the construction and use of protein
      description sentences.
AB  - Existing biological knowledge stored as structured database records has been
      extracted manually by database curators analyzing the scientific literature. Most
      of this information was derived from sentences which describe biologically
      relevant aspects of genes and gene products. We introduce the Protein description
      sentence (Prodisen) corpus, a useful resource for the automatic identification
      and construction of text-based protein and gene description records using
      information extraction and text classification techniques. Basic guidelines and
      criteria relevant for the construction of a text corpus of functional
      descriptions of genes and proteins are proposed. The steps used for the corpus
      construction and its features are presented. Moreover, some of the potential
      applications of the Prodisen corpus for biomedical text mining purposes are
      explored and the obtained results are presented.

PMID- 17503386
TI  - Assessing clustering results with reference taxonomies.
AB  - The comparative analysis of phylogenies obtained using different phylogenetic
      methods or different gene sequences for a given set of species, is usually done
      by computing some quantitative measure of similarity between the phylogenetic
      trees. Such a quantitative approach provides little insight into the actual
      similarities and differences between the alternative phylogenies. In this paper,
      we present a method for the qualitative assessment of a phylogenetic tree against
      a reference taxonomy, based on highlighting their common clusters. Our algorithms
      build a reference taxonomy for the taxa present in a given phylogenetic tree and
      produce a dendogram for the input phylogenetic tree, with branches in those
      clusters common to the reference taxonomy highlighted. Our implementation of the
      algorithms produces publication-quality graphics. For unrooted phylogenies, the
      method produces a radial cladogram for the input phylogenetic tree, with branches
      in common clusters to the reference taxonomy highlighted.

PMID- 17503387
TI  - Pairwise alignment with rearrangements.
AB  - The increase of available genomes poses new optimization problems in genome
      comparisons. A genome can be considered as a sequence of characters (loci) which
      are genes or segments of nucleotides. Genomes are subject to both nucleotide
      transformation and character order rearrangement processes. In this context, we
      define a problem of so-called pairwise alignment with rearrangements (PAR)
      between two genomes. The PAR generalizes the ordinary pairwise alignment by
      allowing the rearrangement of character order. The objective is to find the
      optimal PAR that minimizes the total cost which is composed of three factors: the
      edit cost between characters, the deletion/insertion cost of characters, and the
      rearrangement cost between character orders. To this end, we propose simple and
      effective heuristic methods: character moving and simultaneous character
      swapping. The efficiency of the methods is tested on Metazoa mitochondrial
      genomes. Experiments show that, pairwise alignments with rearrangements give
      better performance than ordinary pairwise alignments without rearrangements. The
      best proposed method, simultaneous character swapping, is implemented as an
      essential subroutine in our software POY version 4.0 to reconstruct genome-based
      phylogenies.

PMID- 17503388
TI  - Techniques for multi-genome synteny analysis to overcome assembly limitations.
AB  - Genome scale synteny analysis, the analysis of relative gene-order conservation
      between species, can provide key insights into evolutionary chromosomal dynamics,
      rearrangement rates between species, and speciation analysis. With the rapid
      availability of multiple genomes, there is a need for efficient solutions to aid
      in comparative syntenic analysis. Current methods rely on homology assessment and
      multiple alignment based solutions to determine homologs of genetic markers
      between species and to infer syntenic relationships. One of the primary
      challenges facing multi-genome syntenic analysis is the uncertainty posed by
      genome assembly data with un-sequenced gaps and possible assembly errors.
      Currently, manual intervention is necessary to tune and correct the results of
      homology assessment and synteny inference. This paper presents a novel automated
      approach to overcome some of these limitations. It uses a graph based algorithm
      to infer sub-graphs denoting synteny chains with the objective of choosing the
      best locations for homologous elements, in the presence of paralogs, in order to
      maximize synteny. These synteny chains are expanded by merging sub-graphs based
      on various user defined thresholds for micro-syntenic scrambling. This approach
      comprehends and accommodates for contig and scaffold gaps in the assembly to
      determine homologous genetic elements that might either fall in unsequenced
      assembly gaps or lie on the edges of sequenced segments or on small fragments.
      Furthermore, it provides an automated solution for breakpoint analysis and a
      comparative study of chromosomal rearrangements between species. This approach
      was applied to a comparative study involving Drosophila.melanogaster and
      Drosophila.pseudoobscura genomes, as an example, and has been useful in analyzing
      inter-species syntenic relationships.

PMID- 17503389
TI  - A Markov chain model for haplotype assembly from SNP fragments.
AB  - Single nucleotide polymorphism (SNP) is the most frequent form of human genetic
      variations and of importance for medical diagnosis and tracking disease genes. A
      haplotype is a sequence of SNPs from a single copy of a chromosome, and haplotype
      assembly from SNP fragments is based on DNA fragments with SNPs and the
      methodology of shotgun sequence assembly. In contrast to conventional
      combinatorial models which aim at different error types in SNP fragments, in this
      paper we propose a new statistical model - a Markov chain model for haplotype
      assembly based on information of SNP fragments. The main advantage of this model
      over combinatorial ones is that it requires no prior information on error types
      in data. In addition, unlike exact algorithms with the exponential-time
      computation complexity for most combinatorial models, the proposed model can be
      solved in polynomial time and thus is efficient for large-scale problems.
      Experiment results on several data sets illustrate the effectiveness of the new
      method.

PMID- 17503390
TI  - MetaClustering: discovery of the different sample clusterings in gene expression
      data.
AB  - Clustering of the samples is a standard procedure for the analysis of gene
      expression data, for instance to discover cancer subtypes. However, more than one
      biologically meaningful clustering can exist, depending on the genes chosen. We
      propose here to group the genes in function of the clustering of the samples they
      fit. This allows to determine directly the different clusterings of the samples
      present in the data. As a clustering is a structure, genes belonging to the same
      group are functions of the same structure. Hence, the determination of groups of
      genes which support the same clustering could also be viewed as the detection of
      non-linearly linked genes. MetaClustering was applied successfully to simulated
      data. It also recovered the known clustering of real cancer data, which was
      impossible using the complete set of genes. Finally, it clustered together cell
      cycle genes, showing its ability to group genes related in a non-linear way.

PMID- 17503391
TI  - Biomarkers for epithelial ovarian cancers.
AB  - Epithelial carcinoma of the ovary is one of the most common gynecological
      malignancies and the fifth most frequent cause of cancer death in women.
      Currently blood test of advanced epithelial tumors are reflected in a high level
      of CA 125 antigen. However, it is not a good marker for early stage tumors, and
      may yield false positives. Clearly, there is a need for better understanding of
      the molecular pathogenesis of epithelial ovarian cancer, so that new drug targets
      or biomarkers that facilitate early detection can be identified. This work
      concentrates on finding genetic markers for three epithelial ovarian tumors,
      using a simple computational method. We give a small set of genetic markers which
      are able to distinguish clear cell and mucinous ovarian cancers (13 and 26 genes
      respectively) from other epithelial ovarian tumors with 100% accuracy. We obtain
      the genes HNF1-beta (TCF2) and GGT1 as the best markers for the clear cell and
      CEACAM6 (NCA) as the best marker for mucinous ovarian tumors. We employ a feature
      selection technique based on minimum probability of error for this purpose. We
      give a ranking of the important genes responsible for these tumors and validate
      the results using the leave-one-out cross-validation technique. Using this
      method, we also agree with the common notion that WT1 is one of the best genes to
      separate serous ovarian tumors from other epithelial ovarian tumors.

PMID- 17503392
TI  - PepSOM: an algorithm for peptide identification by tandem mass spectrometry based
      on SOM.
AB  - Peptide identification by tandem mass spectrometry is both an important and
      challenging problem in proteomics. At present, huge amount of spectrum data are
      generated by high throughput mass spectrometers at a very fast pace, but
      algorithms to analyze these spectra are either too slow, not accurate enough, or
      only gives partial sequences or sequence tags. In this paper, we emphasize on the
      balance between identification completeness and efficiency with reasonable
      accuracy for peptide identification by tandem mass spectrum. Our method works by
      converting spectra to vectors in high-dimensional space, and subsequently use
      self-organizing map (SOM) and multi-point range query (MPRQ) algorithm as a
      coarse filter reduce the number of candidates to achieve efficient and accurate
      database search. Experiments show that our algorithm is both fast and accurate in
      peptide identification.

PMID- 17503393
TI  - DAPID: a 3D-domain annotated protein-protein interaction database.
AB  - DAPID is a database of domain-annotated protein interactions inferred from three
      dimensional (3D) interacting domains of protein complexes in the Protein Data
      Bank (PDB). The DAPID data model allows users to visualize 3D interacting
      domains, contact residues, and molecular details of any predicted protein-protein
      interactions. Our model derives these interactions by utilizing a new concept,
      called the ''3D-domain interologs'' which is similar to ''interologs''. In S.
      cerevisiae, there is 18.6% overlap between our predicted protein-protein
      interactions and ones in the DIP database. The mean correlation coefficient of
      the gene expression profiles of our predicted interactions is significantly
      higher than that for random pairs in S. cerevisiae. In addition, we find several
      novel interactions which are consistent with the functions of the proteins. The
      DAPID currently holds 1008 3D-interacting domain pairs and 101511 predicted 3D
      domain annotated protein-protein interactions. It is available online at
      http://gemdock.life.nctu.edu.tw/dapid.

PMID- 17503394
TI  - A method to detect important residues using protein binding site comparison.
AB  - As the number of protein sequences with unknown function increases, assigning
      accurate function to unknown protein becomes increasingly an important issue.
      Protein function is often encoded in a small number of residues located in
      binding pocket, and there have been many attempts to predict the function using
      the binding site. Here, we developed a binding site comparison method which can
      easily identify spatially matched residues between binding sites. Using clique
      detection algorithm, the new method finds the matched residues of maximum size,
      and then these matched residues are scored in a way similar to sequence alignment
      scoring. In addition, the significance of matched score is estimated from the
      empirical random score distribution. Results of benchmark test suggest that the
      method successfully detects functionally related binding sites. Furthermore,
      conserved residues and subfamily-specific residues in the functional family can
      be identified. In addition, we investigated systematic relationship between
      binding sites and functions using the binding site comparison method. Result
      showed that proteins with similar binding site largely perform similar function.

PMID- 17503395
TI  - Modeling and estimation of dynamic EGFR pathway by data assimilation approach
      using time series proteomic data.
AB  - Cell Illustrator is a model building tool based on the Hybrid Functional Petri
      net with extension (HFPNe). By using Cell Illustrator, we have succeeded in
      modeling biological pathways, e.g., metabolic pathways, gene regulatory networks,
      microRNA regulatory networks, cell signaling networks, and cell-cell
      interactions. The recent development of tandem mass spectrometry coupled with
      liquid chromatography (LC/MS/MS) technology has enabled researchers to quantify
      the dynamic profile of a wide range of proteins within the cell. The proteomic
      data obtained by using LC/MS/MS has been considerably useful for introducing
      dynamics to the HFPNe model. Here, we report the first introduction of the time
      series proteomic data to our HFPNe model. We constructed an epidermal growth
      factor receptor signal transduction pathway model (EFGR model) by using the
      biological data available in the literature. Then, the kinetic parameters were
      determined in the data assimilation (DA) framework with some manual tuning so as
      to fit the proteomic data published by Blagoev et al. (Nat. Biotechnol., 22:1139
      1145, 2004). This in silico model was further refined by adding or removing some
      regulation loops using biological background knowledge. The DA framework was used
      to select the most plausible model from among the refined models. By using the
      proteomic data, we semi-automatically constructed a well-tuned EGFR HFPNe model
      by using the Cell Illustrator coupled with the DA framework.

PMID- 17503396
TI  - A large-scale computational approach to drug repositioning.
AB  - We have developed a computational pipeline for the prediction of protein-small
      molecule interactions and have applied it to the drug repositioning problem
      through a large-scale analysis of known drug targets and small molecule drugs.
      Our pipeline combines forward and inverse docking, the latter of which is a twist
      on the conventional docking procedure used in drug discovery: instead of docking
      many compounds against a specific target to look for potential inhibitors, one
      compound is docked against many proteins to search for potential targets. We
      collected an extensive set of 1,055 approved small molecule drugs and 1,548 drug
      target binding pockets (representing 78 unique human protein therapeutic targets)
      and performed a large-scale docking using ICM software to both validate our
      method and predict novel protein-drug interactions. For the 37 known protein-drug
      interactions in our data set that have a known structure complex, all docked
      conformations were within 2.0A of the solved conformation, and 30 of these had a
      docking score passing the typical ICM score threshold. Out of the 237 known
      protein-drug interactions annotated by DrugBank, 74 passed the score threshold,
      and 52 showed the drug docking to another protein with a better docking score
      than to its known target. These protein targets are implicated in human diseases,
      so novel protein-drug interactions discovered represent potential novel
      indications for the drugs. Our results highlight the promising nature of the
      inverse docking method for identifying potential novel therapeutic uses for
      existing drugs.

PMID- 17503397
TI  - A generalized threading model using integer programming that allows for secondary
      structure element deletion.
AB  - Integer programming is a combinatorial optimization method that has been
      successfully applied to the protein threading problem. We seek to expand the
      model optimized by this technique to allow for a more accurate description of
      protein threading. We have developed and implemented an expanded model of integer
      programming that has the capability to model secondary structure element
      deletion, which was not possible in previous version of integer programming based
      optimization.

PMID- 17503398
TI  - Protein topology classification using two-stage support vector machines.
AB  - The determination of the first 3-D model of a protein from its sequence alone is
      a non-trivial problem. The first 3-D model is the key to the molecular
      replacement method of solving phase problem in x-ray crystallography. If the
      sequence identity is more than 30%, homology modelling can be used to determine
      the correct topology (as defined by CATH) or fold (as defined by SCOP). If the
      sequence identity is less than 25%, however, the task is very challenging. In
      this paper we address the topology classification of proteins with sequence
      identity of less than 25%. The input information to the system is amino acid
      sequence, the predicted secondary structure and the predicted real value relative
      solvent accessibility. A two stage support vector machine (SVM) approach is
      proposed for classifying the sequences to three different structural classes
      (alpha, beta, alpha+beta) in the first stage and 39 topologies in the second
      stage. The method is evaluated using a newly curated dataset from CATH with
      maximum pairwise sequence identity less than 25%. An impressive overall accuracy
      of 87.44% and 83.15% is reported for class and topology prediction, respectively.
      In the class prediction stage, a sensitivity of 0.77 and a specificity of 0.91 is
      obtained. Data file, SVM implementation (SVMHEAVY) and result files can be
      downloaded from http://www.ee.unimelb.edu.au/ISSNIP/downloads/.

PMID- 17503399
TI  - Robotic path planning and protein complex modeling considering low frequency
      intra-molecular loop and domain motions.
AB  - A novel algorithm is introduced to deal with intra-molecular motions of loops and
      domains that undergo proteins at interaction with other proteins. The methodology
      is based on complex energy landscape sampling and robotic motion planning.
      Mapping high flexibility regions on the protein underlies the proposed algorithm.
      This is the first time this type of research has been reported. Application of
      the methodology to several protein complexes where remarkable backbone
      rearrangement is observed shows that the new algorithm is able to deal with the
      problem of change of backbone conformation at protein interaction. We have
      implemented the module within the system MIAX (Macromolecular interaction
      assessment computer system) and together with our already reported soft and
      flexible docking algorithms we have developed a powerful tool for protein
      function analysis as part of wide genome function evaluation.

PMID- 17503400
TI  - Delayed behavioral and endocrine effects of sarin and stress exposure in mice.
AB  - The organophosphorus agent sarin is a potent inhibitor of acetylcholinesterase.
      Experiments tested the influence of exposure to low doses of sarin along with
      psychological stress on delayed behavioral and endocrine changes in mice. Motor
      activity, acoustic startle response (ASR), pre-pulse inhibition (PPI) of ASR,
      activity of cholinesterase in blood and catecholamine levels in adrenals were
      evaluated after low dose sarin exposure (3 x 0.4 LD50 subcutaneously) combined
      with chronic intermittent stress in C57BL/6J mice. While sarin alone produced
      depression of motor activity, no interaction of the stress with sarin exposure
      was observed. Cholinesterase activity was significantly reduced 24 h after
      exposure to sarin; however, the basal activity was re-established 3 weeks later.
      The combination of low dose sarin exposure and stress produced delayed behavioral
      change manifested as excessive grooming together with endocrine alterations in
      adrenals 7 weeks after exposure. The size of the adrenals in the combined
      exposure group was increased and the concentration of catecholamines was
      significantly decreased. In conclusion, these findings indicate that sarin in low
      doses is more dangerous when combined with shaker stress inducing delayed
      behavioral and endocrine changes.

PMID- 17503401
TI  - Ovicidal and larvicidal effectiveness of insecticides applied by dipping apples
      on the small fruit tortrix Grapholita lobarzewskii.
AB  - The larvicidal and ovicidal effectiveness of twelve insecticides on Grapholita
      lobarzewskii Nowicki was tested by dipping apples in different concentrations of
      the insecticides. Emamectin was the most effective larvicidal product, with an
      LC(50) of 0.01 mg kg(-1), closely followed by spinosad, methoxyfenozide and
      chlorpyrifos-methyl, with LC(50) values between 0.2 and 0.7 mg kg(-1). Products
      like imidacloprid, indoxacarb, phosmet and thiacloprid gave LC(50) values between
      1 and 2 mg kg(-1). Lastly, chlorpyrifos-ethyl and phosalone had LC(50) values of
      around 4 mg kg(-1), whereas tebufenozide and diflubenzuron had almost no
      larvicidal effect. Most of the products tested had low ovicidal effectiveness,
      and only fenoxycarb and emamectin gave LC(50) values worthy of note, close to 2
      mg kg(-1).

PMID- 17503402
TI  - Detection of recombinant human erythropoietin in urine for doping analysis:
      interpretation of isoelectric profiles by discriminant analysis.
AB  - The detection in urine of recombinant human erythropoietin (rHuEPO), a hormone
      misused by endurance athletes as a doping agent, is based on the differentiation
      of its isoelectric pattern from that of the corresponding natural hormone.
      Different empirical criteria have been proposed for discriminating the images of
      the patterns but none of them have been elaborated from a rational statistical
      approach. Discriminant analysis was applied to a dataset of profiles defined as
      positive (116 profiles from 26 subjects) (presence of rHuEPO and possibly
      residual natural endogenous hormone) and negative (131 profiles from 131
      subjects) (presence of natural endogenous hormone only). The different bands were
      numbered according to a template of 16 possible positions and their relative
      intensities constituted the 16 variables of the statistical analysis. This method
      was then tested with data from an administration trial of low doses (6.7-10
      IU/kg) following high-dose (265 IU/kg) injections (71 profiles from one subject).
      The analysis of the dataset clearly separated the negative and positive profiles.
      A cross-validation procedure confirmed that the analysis was extremely stable:
      with ten-fold cross-validation, no false positives were observed even with
      100,000 simulations. Furthermore, the detection of rHuEPO in the profiles from
      the low-dose trial was greatly improved in comparison with a previously validated
      empirical criterion.

PMID- 17503403
TI  - Expression of high-abundance proteins in sera of patients with endometrial and
      cervical cancers: analysis using 2-DE with silver staining and lectin detection
      methods.
AB  - The expression of high-abundance serum proteins in newly diagnosed patients with
      endometrial adenocarcinoma (EACa), squamous cell cervical carcinoma (SCCa) and
      cervical adenocarcinoma (ACCa), relative to control female subjects, was analyzed
      by subjecting serum samples to 2-DE followed by image analysis of the silver
      stained protein profiles. The three cohorts of cancer patients demonstrated
      different altered expression of serum high-abundance proteins compared to
      negative control women. The expression of alpha1-antitrypsin, alpha1-B
      glycoprotein, cleaved high-molecular-weight kininogen (light chain) and
      antithrombin III were consistently altered in all the patients. However,
      clusterin was upregulated only in the patients with EACa, while those with SCCa
      and ACCa were typically characterized by the upregulated expression of zinc alpha
      2-glycoprotein. The aberrant expression of selective serum proteins in the
      various cohorts of cancer patients was validated by competitive ELISA as well as
      by lectin detection. Analysis by using the champedak galactose binding lectin
      further highlighted an unidentified protein that may be differently glycosylated
      in the sera of the EACa patients that were studied.

PMID- 17503404
TI  - The role of electrophoresis in disease biomarker discovery.
AB  - There has been increased activity in the last few years in the search for disease
      markers using fractionation of complex biological fluids combined with MS. While
      electrophoretic and chromatographic separations have played a major role in this
      endeavor, this manuscript is limited to a review of electrophoretic methods that
      have been established for disease biomarker discovery. These methods include 2
      DE, difference gel electrophoresis (DIGE), and CE. We define what constitutes a
      biomarker, identify the steps required for establishing a biomarker, and describe
      the parameters needed in the design of an ideal diagnostic test. The application,
      advantages, and limitations of CE, DIGE, and 2-DE in meeting the goal of
      discovering novel biomarkers is discussed in detail, along with a few selected
      examples that illustrate the search for biomarkers for cancer and neurological
      diseases.

PMID- 17503405
TI  - Genetic microheterogeneity of human transthyretin detected by IEF.
AB  - Mutations of the human transthyretin (TTR) gene have attracted medical interest
      as a cause of amyloidosis. Recently, we have described in detail an
      electrophoretic procedure with PAGE followed by IEF in urea gradients for the
      study of the microheterogeneity of TTR monomers (Altland, K., Winter, P.,
      Sauerborn, M. K., Electrophoresis 1999, 20, 1349-1364). In this paper, we present
      a study on 49 different mutations of TTR including 33 that result in electrically
      neutral amino acid substitutions. The aims of the investigation were to test the
      sensitivity of the procedure to detect TTR variants in patients with TTR
      amyloidosis and their relatives and to identify some common characteristics that
      could explain the amyloidogenicity of these variants. We found that all tested
      amyloidogenic mutations could be detected by our method with the exception of
      those for which the corresponding variant was absent in plasma samples. Most of
      the electrically neutral amyloidogenic TTR variants had in common a reduced
      conformational stability of monomers by the activity of protons and urea. For
      three variants, e.g. TTR-F64L, TTR-I107V and TTR-V122I, the monomers had a
      conformational stability close to that of normal monomers but we found
      experimental and structural arguments for a weakening of the monomer-monomer
      contact. All types of amyloidogenic mutations affected the stability of TTR
      tetramers.

PMID- 17503406
TI  - Systematically probing the effect of catalyst acidity in a hydrogen-bond
      catalyzed enantioselective reaction.

PMID- 17503407
TI  - Total synthesis of the thiazolyl peptide GE2270 A.

PMID- 17503408
TI  - Fabrication of cellular multilayers with nanometer-sized extracellular matrix
      films.

PMID- 17503409
TI  - Proteins involved in neuronal differentiation of neuroblastoma cell line N1E-115.
AB  - Neuronal differentiation (ND) represents a well-defined phenomenon in biological
      terms but proteins involved have not been studied systematically. We therefore
      aimed to study ND by retinoic acid (RA) in a widely used neuroblastoma cell line
      by comparative proteomics. The ND was induced in the N1E-115 cell line by serum
      deprivation and RA treatment. Undifferentiated cells and cells undergoing serum
      deprivation served as controls. Protein extracts were run on 2-DE followed by
      MALDI-TOF or MALDI-TOF-TOF analysis. Quantification was carried out using
      specific software and stringent statistical analysis was performed. Tubulin beta
      5, cat eye syndrome critical region protein 5 homolog, putative GTP-binding
      protein PTD004 homolog, and the metabolic proteins glyceraldehyde-3-phosphate
      dehydrogenase and transketolase were differentially regulated. Differential
      protein levels of cytoskeleton proteins including tubulins and metabolic proteins
      have been reported to be regulated by ND. Herein, specific signaling differences
      as reflected by putative GTP-binding protein PTD004 changes in differentiated
      cells are shown and a possible role for the Cat eye syndrome critical region
      protein 5 homolog is proposed. The protein disulfide isomerase associated 3
      protein fits the already proposed findings of chaperon regulation by ND. The
      study forms the molecular basis for further evaluation of the functional roles of
      the differentially expressed proteins in ND.

PMID- 17503410
TI  - The effect of adrenomedullin on rats exposed to lead.
AB  - Adrenomedullin (AdM) was originally discovered as a vasorelaxant peptide. The
      antioxidative properties of AdM have been reported recently. Through its
      antioxidative effect, adrenomedullin can protect organs from damage induced by
      stressors. Lead, commonly detected in air, soil, water and food, is a major
      source of oxidative stress. The effect of AdM in the liver of rats exposed to
      lead was investigated. Twenty-four female Wistar rats were divided into four
      groups: a control group (C), adrenomedullin group (AdM), lead (Pb) group and lead
      + adrenomedullin (Pb + AdM) group. In the Pb-treated groups, the animals were
      exposed to lead in drinking water containing 250 ppm PbCl2 for 4 weeks. In the
      AdM-treated group, the animals received an i.p. injection of AdM (3000 ng kg(-1)
      body weight) in the third week of lead treatment for 1 week. The activities of
      catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)
      and the level of malondialdehyde (MDA) were determined in the liver of rats.
      Histological changes in the liver were examined by light and electron microscopy
      as well. The MDA levels were increased significantly in the Pb-treated groups,
      but in the Pb + AdM group the MDA levels were decreased significantly when
      compared with the Pb group. AdM reduced hepatic damage in the Pb + AdM group, but
      the difference in the total histopathological scores between the Pb and Pb + AdM
      groups was not significant. When the results are taken together, it can be
      concluded that AdM may have protective or compensating effects in lead toxicity.

PMID- 17503411
TI  - Decreased expression level of SH2 domain-containing protein tyrosine phosphatase
      1 (Shp1) is associated with progression of chronic myeloid leukaemia.
AB  - Chronic myeloid leukaemia (CML) is characterized by t(9;22)(q34;q11) and the
      aberrant expression of the fusion protein Bcr-Abl that leads to constitutive
      activation of c-Abl kinase. Bcr-Abl plays a major role in the development and
      progression of CML through chronic, accelerated, and blast phases. The
      interaction between Bcr-Abl and other oncogenic molecules has been extensively
      documented. Nonetheless, negative regulatory mechanisms of Bcr-Abl are not
      completely defined. One major inhibitory pathway is mediated via the SH2 domain
      containing protein tyrosine phosphatase Shp1. In the present study, we
      demonstrate that Shp1 levels are markedly decreased in advanced stage CML
      patients compared with those in chronic phase. This process was independent of
      DNA methylation. Furthermore, we did not detect mutations in the Shp1 gene in CML
      cell lines or patient samples. These data suggest that the decrease in Shp1 in
      advanced stage CML patients is due to post-transcriptional modifications. Our
      findings suggest that the decrease in Shp1 expression levels plays a role in the
      progression of CML. Also, the decrease in Shp1 and subsequently its inhibitory
      effect on Bcr-Abl could provide an explanation for imatinib resistance seen in
      advanced stage CML patients.

PMID- 17503412
TI  - Neuropilins in physiological and pathological angiogenesis.
AB  - Neuropilin-1 (Np1) and neuropilin-2 (Np2) are transmembrane glycoproteins with
      large extracellular domains that interact with both class 3 semaphorins and
      vascular endothelial growth factor (VEGF), and are involved in the regulation of
      many physiological pathways, including angiogenesis. The neuropilins also
      interact directly with the classical receptors for VEGF, VEGF-R1 and -R2,
      mediating signal transduction. The heart, glomeruli and osteoblasts express both
      Np1 and Np2, but there is differential expression in the adult vasculature, with
      Np1 expressed mainly by arterial endothelium, whereas Np2 is only expressed by
      venous and lymphatic endothelium. Both neuropilins are commonly over-expressed in
      regions of physiological (wound-healing) and pathological (tumour) angiogenesis,
      but the signal transduction pathways, neuropilin-mediated gene expression and the
      definitive role of neuropilins in angiogenic processes are not fully
      characterized. This review details the current evidence for the role of
      neuropilins in angiogenesis, and suggests future research directions that may
      enhance our understanding of the mechanisms of action of this unique family of
      proteins.

PMID- 17503413
TI  - Molecular classification and genetic pathways in hyperplastic polyposis syndrome.
AB  - Hyperplastic Polyposis (HPPS) is a poorly characterized syndrome that increases
      colorectal cancer (CRC) risk. We aimed to provide a molecular classification of
      HPPS. We obtained 282 tumours from 32 putative HPPS patients with >or= 10
      hyperplastic polyps (HPs); some patients also had adenomas and CRCs. We found no
      good evidence of microsatellite instability (MSI) in our samples. The epithelium
      of HPs was monoclonal. Somatic BRAF mutations occurred in two-thirds of our
      patients' HPs, and KRAS2 mutations in 10%; both mutations were more common in
      younger cases. The respective mutation frequencies in a set of 'sporadic' HPs
      were 18% and 10%. Importantly, the putative HPPS patients generally fell into two
      readily defined groups, one set whose polyps had BRAF mutations, and another set
      whose polyps had KRAS2 mutations. The most plausible explanation for this
      observation is that there exist different forms of inherited predisposition to
      HPPS, and that these determine whether polyps follow a BRAF or KRAS2 pathway.
      Most adenomas and CRCs from our putative HPPS patients had 'classical' morphology
      and few of these lesions had BRAF or KRAS2 mutations. These findings suggest that
      tumourigenesis in HPPS does not necessarily follow the 'serrated' pathway.
      Although current definitions of HPPS are sub-optimal, we suggest that diagnosis
      could benefit from molecular analysis. Specifically, testing BRAF and KRAS2
      mutations, and perhaps MSI, in multiple polyps could help to distinguish HPPS
      from sporadic HPs. We propose a specific model which would have diagnosed five
      more of our cases as HPPS compared with the WHO clinical criteria.

PMID- 17503414
TI  - Overexpression of the alpha v beta 6 integrin in cervical squamous cell carcinoma
      is a prognostic factor for decreased survival.
AB  - Cervical squamous cell carcinomas are composed histologically of tumour cell
      islands surrounded by varying amounts of tumour stroma, the amount and
      composition of which are influenced by local TGF-beta(1). TGF-beta(1) is secreted
      in an inactive complex with latency-associated peptide (LAP). Both LAP and the
      extracellular matrix (ECM) protein fibronectin are important ligands for the
      integrin receptor alpha v beta 6. While alpha v beta 6 is only weakly expressed
      by normal epithelia, it is up-regulated in different carcinomas where it
      generally reflects a more aggressive phenotype. In cervical cancer, the
      expression of alpha v beta 6 has not thus far been investigated. Given the
      ability of alpha v beta 6 both to activate TGF-beta(1) and to interact with
      fibronectin, we studied correlations between the expression of these components
      and disease parameters in a large cohort of cervical cancer specimens. We
      analysed alpha v beta 6 expression using immunohistochemistry in primary cervical
      squamous carcinomas of FIGO stage IA to IIB patients and correlated the findings
      with formerly investigated fibronectin and TGF-beta(1) expression and clinico
      pathological parameters. alpha v beta 6 expression was also examined in cervical
      intra-epithelial neoplasia (CIN) and lymph node metastases. alpha v beta 6 was
      only weakly expressed in normal epithelium but clearly up-regulated in CIN
      lesions. In carcinomas, strong expression of alpha v beta 6 in tumour cells
      correlated with different clinico-pathological parameters and with worse overall
      and disease-free survival. Furthermore, alpha v beta 6 expression correlated
      positively with TGF-beta(1) mRNA expression as well as with fibronectin
      expression. Overexpression of alpha v beta 6 in cervical squamous carcinomas is
      an unfavourable prognostic factor. This might reflect an increased capacity of
      alpha v beta 6-expressing tumour cells to migrate in a fibronectin-rich ECM
      and/or to activate TGF-beta(1) at the tumour/stroma interface, both of which
      processes may contribute to cervical cancer progression.

PMID- 17503415
TI  - Highly diastereoselective lithiation and substitution of an (S)-prolinyl
      thiocarbamate via sterically homogeneous lithio(thiocarbamate): synthesis of
      enantiomerically pure prolinethiols.
AB  - Highly diastereoselective lithiation-substitution reactions of an (S)-proline
      derived S-alkyl thiocarbamate was accomplished. The configuration of the
      predominant alkyllithium species and the stereochemical course of the
      electrophilic substitution reactions are deduced by a combination of X-ray
      crystal structure analysis, NMR spectroscopic studies, deuteration/dedeuteration
      experiments, and quantum chemical calculations. The lithium intermediate (S,S)-9
      was found to be kinetically and thermodynamically favoured, whereas (S,R)-9
      rapidly epimerizes.

PMID- 17503416
TI  - Synthetic models of the active site of cytochrome C oxidase: influence of
      tridentate or tetradentate copper chelates bearing a His--Tyr linkage mimic on
      dioxygen adduct formation by heme/Cu complexes.
AB  - Two synthetic models of the active site of cytochrome c oxidase--[(LN4-OH)CuI
      FeII(TMP)]+ (1 a) and [(LN3-OH)CuI-FeII(TMP)]+ (2 a)-have been designed and
      synthesized. These models each contain a heme and a covalently attached copper
      moiety supported either by a tetradentate N4-copper chelate or by a tridentate N3
      copper chelate including a moiety that acts as a mimic of the crosslinked His-Tyr
      component of cytochrome c oxidase. Low-temperature oxygenation reactions of these
      models have been investigated by spectroscopic methods including UV/Vis,
      resonance Raman, ESI-MS, and EPR spectroscopy. Oxygenation of the tetradentate
      model 1 a in MeCN and in other solvents produces a low-temperature-stable
      dioxygen-bridged peroxide [(LN4-OH)CuII-O2-FeIII(TMP)]+ {nuO--O=799 (16O2)/752
      cm(-1) (18O2)}, while a heme superoxide species [(TMP)FeIII(O2-)CuIILN3-OH] {nuFe
      -O2: 576 (16O2)/551 cm(-1) (18O2)} is generated when the tridentate model 2 a is
      oxygenated in EtCN solution under similar experimental conditions. The
      coexistence of a heme superoxide species [(TMP)FeIII(O2-)CuIILN3-OH] and a
      bridged peroxide [(LN3-OH)CuII-O2-FeIII(TMP)]+ species in equal amounts is
      observed when the oxygenation reaction of 2 a is performed in CH2Cl(2)/7 % EtCN,
      while the percentage of the peroxide (approximately 70 %) in relation to
      superoxide (approximately 30 %) increases further when the crosslinked phenol
      moiety in 2 a is deprotonated to produce the bridged peroxide [(LN3-OH)CuII-O2
      FeIII(TMP)]+ {nuO--O: 812 (16O2)/765 cm(-1) (18O2)} as the main dioxygen
      intermediate. The weak reducibility and decreased O2 reactivity of the
      tricoordinated CuI site in 2 a are responsible for the solvent-dependent
      formation of dioxygen adducts. The initial binding of dioxygen to the copper site
      en route to the formation of a bridged heme-O2-Cu intermediate by model 2 a is
      suggested and the deprotonated crosslinked His-Tyr moiety might contribute to
      enhancement of the O2 affinity of the CuI site at an early stage of the dioxygen
      binding process.

PMID- 17503417
TI  - Cytotoxic polyketides containing tetramic acid moieties isolated from the fungus
      Myceliophthora Thermophila: elucidation of the relationship between cytotoxicity
      and stereoconfiguration.
AB  - Five new polyketides that contain tetramic acids, myceliothermophins A-E, were
      isolated from the thermophilic fungus Myceliophthora thermophila. Two sets of 5
      alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one diastereomers,
      myceliothermophins A/B and C/D, were separated as pure compounds by using silica
      gel column chromatography and recycling reverse-phase high-performance liquid
      chromatography (RP-HPLC). The relative configurations of the chiral centers in 5
      alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one moieties were deduced from
      NOESY correlations. In the cytotoxic assay, the 5-(2-methylpropyldiene)-1H-pyrrol
      2(5H)-one analogue (myceliothermophin E) exhibited inhibition against four cancer
      cell lines. In addition, the significant inhibitory effect of myceliothermophins
      A and C and the inactivity of myceliothermophins B and D revealed the importance
      of the relative configurations of 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol
      2(5H)-one moieties on their cytotoxicity potency against cancer cells.

PMID- 17503418
TI  - Stabilization of parallel triplexes by twisted intercalating nucleic acids
      (TINAs) incorporating 1,2,3-triazole units and prepared by microwave-accelerated
      click chemistry.
AB  - A highly efficient method for postsynthetic modification of unprotected
      oligonucleotides incorporating internal insertions of (R)-1-O-(4
      ethynylbenzyl)glycerol has been developed through the application of click
      chemistry with water-insoluble pyren-1-yl azide and water-soluble benzyl azide
      and acceleration by microwave irradiation. The twisted intercalating nucleic
      acids (TINAs) obtained in these reactions, possessing bulged insertions of (R)-3
      O-{4-[1-(pyren-1-yl)-1H-1,2,3-triazol-4-yl]benzyl}glycerol (7), formed parallel
      triplexes with thermal stabilities of 20.0, 34.0, and 40.0 degrees C at pH 7.2 in
      the cases of one, two, or three insertions of 7, respectively, separated by three
      nucleic bases. An oligonucleotide with four insertions of 7--each between three
      nucleic bases in the sequence--was unable to form complexes with complementary
      single- or double-stranded DNAs, as a result of self-aggregation of the pyrene
      moieties. This assumption was supported by the formation of a very strong excimer
      band at 460 nm in the fluorescence spectra. Molecular modeling of the parallel
      triplex with bulged insertion of the monomer 7 in the triplex-forming
      oligonucleotide (TFO) showed that only the pyrene moiety was stacking between the
      bases of the dsDNA, whereas 1,2,3-triazole did not participate in the triplex
      stabilization. Thermal denaturation studies of the duplexes and triplexes, as
      well as the fluorescence properties of TINA-triazole 7, are discussed and
      compared with previous studies on TINA.

PMID- 17503419
TI  - Synthesis of novel 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA)
      derivatives for chemoselective attachment to unprotected polyfunctionalized
      compounds.
AB  - A convenient synthesis of novel bifunctional poly(amino carboxylate) chelating
      agents allowing chemoselective attachment to highly functionalized biomolecules
      is described. Based on the well known chelator 1,4,7,10-tetraazacyclodecane
      1,4,7,10-tetraacetic acid (DOTA), we synthesized novel bifunctional chelating
      agents bearing additional functional groups by alkylating 1,4,7,10
      tetraazacyclododecane (cyclen) with one equivalent of para-functionalized alkyl 2
      bromophenyl-acetate and three equivalents of tert-butyl 2-bromoacetate. The
      resulting compounds, which contain an additional carbonyl or alkyne
      functionality, allow site specific labeling of appropriately functionalized
      unprotected biomolecules in a rapid manner via click reactions. This was
      demonstrated by the attachment of our new DOTA derivatives to the somatostatin
      analogue Tyr3-octreotate by chemoselective oxime ligation and CuI-catalyzed azide
      alkyne cycloaddition. Initial biodistribution studies in mice with the
      radiometalated compound demonstrated the applicability of the described DOTA
      conjugation.

PMID- 17503420
TI  - Membrane protein stoichiometry determined from the step-wise photobleaching of
      dye-labelled subunits.

PMID- 17503421
TI  - Avidin decorated core-shell nanoparticles for biorecognition studies by elastic
      light scattering.
AB  - In this paper, a straightforward method based on elastic light scattering is
      shown to provide a sensitive and reliable tool for the quantitative determination
      of protein-ligand interactions that occur at the surface of suitably designed
      core-shell nanoparticles. The assay makes use of monodisperse nanocolloids that
      have minimal optical contrast with the aqueous environment. By properly coating
      the particles with avidin and oligo(ethylene glycol)-based amphiphiles, we
      developed a hybrid system that combines the availability of standard ligands with
      the necessary bioinvisibility towards the accidental adsorption of nonspecific
      macromolecules. This probe was employed to detect interactions between different
      kinds of biotinylated proteins, and it revealed high specificity and affinities
      in the low nanomolar range. In particular, we obtained an efficient avidin
      anchorage of biotinylated protein A on the surface of the nanoparticles, which we
      exploited as a functional probe for the rapid, quantitative, picomolar detection
      of human IgG antibodies. Overall, these light-scattering-based nanosensors appear
      as a simple and highly informative tool for proteomics studies.

PMID- 17503422
TI  - Exploration of backbone space in foldamers containing alpha- and beta-amino acid
      residues: developing protease-resistant oligomers that bind tightly to the BH3
      recognition cleft of Bcl-xL.
AB  - Protein-protein interactions play crucial roles in cell-signaling events and are
      often implicated in human disease. Molecules that bind tightly to functional
      protein-surface sites and show high stability to degradative enzymes could be
      valuable pharmacological tools for dissection of cell-signaling networks and
      might ultimately lead to therapeutic agents. We recently described oligomers
      containing both alpha- and beta-amino acid residues that bind tightly to the BH3
      recognition site of the anti-apoptotic protein Bcl-x(L). The oligomers with
      highest affinity had a nine-residue N-terminal segment with a 1:1 alpha:beta
      residue repeat and a six-residue C-terminal segment containing exclusively
      proteinogenic alpha-residues. The N-terminal portions of such (alpha/beta+alpha)
      peptides are highly resistant to proteolysis, but the C-terminal alpha-segments
      are susceptible. This study emerged from efforts to modify the alpha-segment in
      an (alpha/beta+alpha)-peptide in a way that would diminish proteolytic
      degradation but retain high affinity for Bcl-x(L). Some of the oligomers reported
      here could prove useful in certain biological applications, particularly those
      for which extended incubation in a biological milieu is required.

PMID- 17503423
TI  - Embedding the amyloid beta-peptide sequence in green fluorescent protein inhibits
      Abeta oligomerization.

PMID- 17503424
TI  - Indirect detection of nitrogen-14 in solid-state NMR spectroscopy.
AB  - NMR spectra of (14)N (spin I=1) are obtained by indirect detection in powders
      spinning at the magic angle. The method relies on the transfer of coherence from
      a neighboring "spy" nucleus with S=1/2, such as (13)C or (1)H, to single- or
      double-quantum transitions of (14)N nuclei. The transfer of coherence can occur
      through a combination of scalar and residual dipolar splittings (RDS); the latter
      are also known as second-order quadrupole-dipole cross terms. The two-dimensional
      NMR spectra reveal powder patterns determined by second- and third-order
      quadrupolar couplings. These spectra depend on the quadrupolar coupling constant
      C(Q) (typically a few megahertz), on the asymmetry parameter eta(Q) of the (14)N
      nucleus, and on the orientation of the internuclear vector r(IS) between the I
      ((14)N) and S (spy) nuclei with respect to the quadrupolar tensor. These
      parameters, which can be subject to motional averaging, can reveal valuable
      information about the structure and dynamics of nitrogen-containing solids.
      Application of this technique to various amino acids, either enriched in (13)C or
      with natural carbon isotope abundance, with spectra recorded at various magnetic
      fields, illustrates the scope of the method.

PMID- 17503425
TI  - Electrochemical and photosensitized redox reactions of a prussian blue film
      layered on a WO3/[Ru(bpy)3]2+/polymer hybrid film.
AB  - A hybrid film of WO(3)/tris(2,2'-bipyridine)ruthenium(II)
      ([Ru(bpy)(3)](2+))/poly(sodium 4-styrenesulfonate) (PSS) (denoted as a WRP hybrid
      film) was prepared as a base layer on an indium tin oxide electrode substrate by
      cathodic electrodeposition from a colloidal ternary solution containing
      peroxotungstic acid, [Ru(bpy)(3)](2+), and PSS. Prussian blue, Fe(III)
      (4)[Fe(II)(CN)(6)](3) (Fe(II)-Fe(III)) was cathodically electrodeposited on the
      WRP hybrid film from a Berlin brown (Fe(III)-Fe(III)) colloidal solution to give
      a WRP/Fe(II)-Fe(III) bilayer film. Spectrocyclic voltammetry measurement of the
      WRP/Fe(II)-Fe(III) bilayer film reveals that Prussian white (Fe(II)-Fe(II)) is
      oxidized to Fe(II)-Fe(III) by electrogenerated Ru(III), and Fe(II)-Fe(III) is re
      reduced to Fe(II)-Fe(II) by electrogenerated H(x)WO(3). Visible-light irradiation
      of the WRP hybrid film generates a small photocurrent (approximately 8 nA cm(-2))
      at 0.4 V of an applied potential, whereas irradiation of the WRP/Fe(II)-Fe(II)
      bilayer film (Fe(II)-Fe(III) is electrochemically reduced to the Fe(II)-Fe(II)
      state) significantly generates a steady photoanodic current of 2.0-1.1 microA cm(
      2) under the same conditions, thus demonstrating that the photoanodic current is
      produced by the layered Fe(II)-Fe(II) film. The photoaction spectrum of the
      bilayer film reveals that the photoanodic current is based on the photoexcitation
      of [Ru(bpy)(3)](2+). The photogeneration of Fe(II)-Fe(III) from Fe(II)-Fe(II) is
      shown by the absorption spectral change of the bilayer film on irradiation. These
      results corroborate the notion that Fe(II)-Fe(II) is oxidized by photogenerated
      Ru(III) to generate Fe(II)-Fe(III). However, the rate of photogeneration of
      Fe(II)-Fe(III) is slow, which could be ascribed to the fast back electron
      transfer (ET) from WO(3) to Ru(III), comparable with the forward ET from Fe(II)
      Fe(II) to Ru(III). The fast back ET could be a crucial problem for the
      [Ru(bpy)(3)](2+)-sensitized reaction in the hybrid film.

PMID- 17503426
TI  - Microfluidic codecs.

PMID- 17503427
TI  - HeLa cell entry by guanidinium-rich beta-peptides: importance of specific cation
      cell surface interactions.
AB  - Short cationic oligomers, including arginine-rich peptides and analogous beta
      amino acid oligomers ("beta-peptides"), can enter the cytoplasm and nucleus of a
      living cell from the extracellular medium. It seems increasingly clear that
      multiple entry pathways are possible, depending upon the structure of the
      guanidinium-rich molecule, the type of cell, and other factors. We have
      previously shown that conformational stability and spatial clustering of
      guanidinium groups increase the HeLa cell entry efficiency of short helical beta
      peptides bearing six guanidinium groups, results that suggest that these beta
      peptides could be useful tools for studying the entry process. Here we describe
      studies intended to identify the point in the entry process at which helix
      stability and spatial arrangement of guanidinium groups exert their effect. Our
      results suggest that key distinctions involve the mode of interaction between
      different guanidinium-rich beta-peptides and the HeLa cell surface. A specific
      guanidinium display appears to be required for proper engagement of cell-surface
      heparan sulfate proteoglycans and concomitant induction of endocytic uptake.

PMID- 17503428
TI  - Diet and breast cancer: a review of the prospective observational studies.
AB  - The role of diet for the risk of breast cancer is of great interest as a
      potentially modifiable risk factor. The evidence from prospective observational
      studies was reviewed and summarized on selected dietary factors, gene-diet
      interactions, and breast cancer incidence. Dietary factors were considered that,
      based on their nutritional constituents, are of particular interest in the
      context of breast cancer: fat intake, biomarkers of fat intake, fruit and
      vegetable consumption, antioxidant vitamins (vitamins A, C, E, and beta
      carotene), serum antioxidants, carbohydrate intake, glycemic index and glycemic
      load, dairy consumption (including vitamin D), consumption of soy products and
      isoflavones, green tea, heterocyclic amines, and adolescent diet. The PubMed
      database was searched for all prospective studies that relate these dietary items
      to the incidence of breast cancer or consider gene-diet interactions. Among the
      prospective epidemiologic studies conducted on diet and breast cancer incidence
      and gene-diet interactions and breast cancer incidence, to date there is no
      association that is consistent, strong, and statistically significant, with the
      exception of alcohol intake, overweight, and weight gain. The apparent lack of
      association between diet and breast cancer may reflect a true absence of
      association between diet and breast cancer incidence or may be due to measurement
      error exceeding the variation in the diet studied, lack of sufficient follow-up,
      and focus on an age range of low susceptibility. The risk of breast cancer can be
      reduced by avoidance of weight gain in adulthood and limiting the consumption of
      alcohol.

PMID- 17503429
TI  - Reported drop in mammography : is this cause for concern?
AB  - BACKGROUND: Timely screening with mammography can prevent a substantial number of
      deaths from breast cancer. The objective of this brief was to ascertain whether
      recent use of mammography has dropped nationally. METHODS: The authors assessed
      the trend in mammography rates from 1987 through 2005. Then, they used the 2000
      and 2005 National Health Interview Survey (NHIS) estimates to characterize trends
      and current patterns in mammography use. RESULTS: After robust, rapid increases
      in reported use of mammography by women in the U.S. since 1987, estimates from
      the 2005 NHIS showed a decline compared with 2000 (from 70% to 66%). Although it
      was small, this decline may be cause for concern, because it signals a change in
      direction. CONCLUSIONS: This report establishes for the nation what already has
      been observed in some local data. The results confirmed that the use of
      mammography may be falling. This change needs to be monitored carefully and also
      may call for intervention.

PMID- 17503430
TI  - Manipulating the chemokine-chemokine receptor network to treat cancer.
AB  - Chemokines are chemoattractant cytokines that regulate the trafficking and
      activation of leukocytes and other cell types under a variety of inflammatory and
      noninflammatory conditions. Over the past few years, studies have increasingly
      shown that chemokines play an important role in several aspects of tumor
      progression. Tumor cells express functional chemokine receptors, which can
      sustain proliferation, angiogenesis, and survival and promote organ-specific
      localization of distant metastases. Chemokine expression in human malignancies is
      associated with a leukocyte infiltration favoring the establishment of immune
      escape mechanisms. A literature review of relevant publications on preclinical
      testing of cancer therapies based on interference with the cancer chemokine
      network was performed. The feasibility, potential advantages, and limitations of
      the clinical translation of the results of such studies in treatment of different
      tumor types and settings are discussed. The chemokine network is a key player in
      the establishment of metastases. In the preclinical setting, blocking agents and
      antibodies directed against CXCR4 prevent metastasis of different cancers. In
      mouse models, overexpression of selected chemokines causes tumor infiltration by
      distinct leukocyte subsets, resulting in tumor regression and tumor-specific
      immunity generation. Researchers have also successfully used chemokines as
      carriers and/or adjuvants for cancer vaccines. The cancer chemokine network is a
      multifaceted therapeutic target.

PMID- 17503431
TI  - Lymphadenectomy in endometrioid uterine cancer staging: how many lymph nodes are
      enough? A study of 11,443 patients.
AB  - BACKGROUND: The purpose of the current study was investigate the association
      between the number of lymph nodes examined and the probability of detecting at
      least a single lymph node involved by metastatic disease in patients with
      endometrioid corpus cancer. METHODS: Demographic, clinicopathologic, and surgical
      information were obtained from the National Cancer Institute between 1990 and
      2001. A logistic regression model was used to investigate the relation between
      the number of lymph nodes identified and the probability of detecting at least a
      single positive lymph node. RESULTS: Of 11,443 patients, the median age was 64
      years (range, 22-74 years). In all, 78.7% had stage I disease, 10.3% had stage II
      disease, and 11.0% had stage III disease; 31.5% had grade 1 histology, 40.6% had
      grade 2 histology, and 24.3% had grade 3 histology. The median number of lymph
      nodes reported was 9 (range, 1-90 lymph nodes). The median number of lymph nodes
      and the percent of patients with positive lymph nodes have increased from 1988 to
      2001. An increasing number of lymph nodes removed was associated with a higher
      likelihood of identifying those with lymph node metastases. Based on the logistic
      regression model, the largest increase in probability of detecting at least a
      single positive lymph node was observed when 21 to 25 lymph nodes were resected
      (odds ratio [OR] of 1.45; 95% confidence interval [95% CI], 1.08-1.94 [P < .01]).
      Removing greater than 25 lymph nodes did not improve the statistical probability
      (OR of 1.23; 95% CI, 0.94-1.61 [P = .13]). CONCLUSIONS: The current study data
      suggest that the removal of 21 to 25 lymph nodes significantly increases the
      probability of detecting at least 1 positive lymph node in endometrioid uterine
      cancer. The definition of an adequate lymphadenectomy deserves further
      investigation.

PMID- 17503432
TI  - Smaller regional volumes of gray and white matter demonstrated in breast cancer
      survivors exposed to adjuvant chemotherapy.

PMID- 17503433
TI  - Rituximab in combination with fludarabine and cyclophosphamide in the treatment
      of patients with recurrent follicular lymphoma.
AB  - BACKGROUND: The current study was conducted to asses the safety profile and
      clinical activity of rituximab in combination with fludarabine and
      cyclophosphamide in patients with recurrent follicular lymphoma (FL). METHODS:
      This study was a noncomparative, multicenter, phase II study. Between March 2000
      and December 2002, 54 patients with recurrent FL were enrolled in the FC+R trial.
      Patients received fludarabine at a dose of 25 mg/m(2) and cyclophosphamide at a
      dose of 300 mg/m(2) daily for 3 consecutive days, every 3 weeks for 4 cycles.
      Rituximab was administered at a dose of 375 mg/m(2) beginning 2 weeks after the
      first course of fludarabine and cyclophosphamide and then on Day 1 of each cycle
      thereafter. The planned treatment duration was 10 weeks. RESULTS: Overall, 92% of
      patients completed the planned therapy in 10 to 14 weeks and 74% achieved a
      complete response (CR). Among patients with BCL2-positive bone marrow, 86%
      obtained a molecular disease remission (MR). The median survival from treatment
      (SFT), the duration of disease remission (DR), and time to disease progression
      (TTP) had not been reached after a median follow-up of 45 months. Of the baseline
      characteristics, >2 previous treatments, BCL2-positive bone marrow, and low
      Follicular Lymphoma International Prognostic Index (FLIPI) score were found to be
      associated with better DR and/or TTP. Hematologic toxicity was transient and
      reversible, with the exception of 3 patients with severe and prolonged
      neutropenia. Three patients presented with infections, 1 of whom died of
      bronchopneumonia. CONCLUSIONS: The FC+R scheme, a nonanthracycline-containing
      regimen lasting up to 10 weeks, was found to be relatively well-tolerated and
      demonstrated significant antilymphoma activity with excellent clinical CR and
      molecular response rates.

PMID- 17503434
TI  - Chemicals causing mammary gland tumors in animals signal new directions for
      epidemiology, chemicals testing, and risk assessment for breast cancer
      prevention.
AB  - Identifying chemical carcinogens in animal studies is currently the primary means
      of anticipating cancer effects in humans. Animal studies to evaluate potential
      chemical carcinogenicity are particularly important for breast cancer because
      environmental and occupational epidemiologic research is sparse. Chemicals that
      increased mammary gland tumors in animal studies were compiled from the
      International Agency for Research on Cancer (IARC), the U.S. National Toxicology
      Program (NTP), and other sources. Summary assessments of the carcinogenic
      potential for each chemical and potentially exposed populations were also
      compiled. In all, 216 chemicals were identified that have been associated with
      increases in mammary gland tumors in at least 1 study. These include industrial
      chemicals, chlorinated solvents, products of combustion, pesticides, dyes,
      radiation, drinking water disinfection byproducts, pharmaceuticals and hormones,
      natural products, and research chemicals. Twenty-nine are produced in the U.S. at
      >1 million pounds/year; 35 are air pollutants, 25 have involved occupational
      exposures to >5000 women, and 73 have been present in consumer products or as
      contaminants of food. Thus, exposure is widespread. Nearly all of the chemicals
      were mutagenic and most caused tumors in multiple organs and species; these
      characteristics are generally believed to indicate likely carcinogenicity in
      humans. To our knowledge, this is the most comprehensive list developed of animal
      mammary gland carcinogens and, along with associated data, is publicly available
      at URL: www.silentspring.org/sciencereview and at URL: www.komen.org/environment.
      Valuable information from cancer bioassays is not well utilized in risk
      assessment and regulatory processes, suggesting a need to strengthen chemicals
      testing and risk assessment as tools for breast cancer prevention.

PMID- 17503435
TI  - Use of health-related and cancer-specific support groups among adult cancer
      survivors.
AB  - BACKGROUND: Data from the National Health Interview Survey suggest that the
      utilization of mental health services among cancer survivors is low and unmet
      needs are high for some. However, to the authors' knowledge little is known
      regarding the prevalence and predictors of participation in health-related
      support groups. METHODS: A total of 9187 participants in the California Health
      Interview Survey Complementary and Alternative Medicine (CHIS-CAM) study
      completed a telephone interview in 2003 (1844 participants with cancer and 4951
      participants with other chronic health problems). Participants were asked to
      describe previous/ current support group use, benefits of support group use, and
      physician involvement in decisions regarding support groups. Weighted logistic
      regression analyses were conducted using SUDAAN software to examine patterns of
      support group use. RESULTS: The prevalence of support group use was found to be
      higher among cancer survivors (23.7%) than those with another chronic health
      condition (14.5%). Predictors of support group use were found to be similar
      across groups and included female gender, greater education, use of complementary
      and alternative medicine (CAM), depression, and anxiety. Age, health insurance,
      and presence of depression predicted support group use differently for cancer
      survivors and those with other conditions. The percentages of those perceiving
      support groups to be beneficial varied from 35.1% for those with skin cancer to
      96% for those with cervical cancer. The percentage of participants reporting that
      their physician recommended a support group was low (10.2%). CONCLUSIONS: Health
      related support groups are used by nearly 1 in 4 cancer survivors, but levels of
      utilization differ across subgroups. An understanding of how cancer survivors use
      support groups highlights shortcomings in psychosocial care and suggests that
      additional efforts to overcome barriers to care are needed.

PMID- 17503436
TI  - Environmental pollutants and breast cancer: epidemiologic studies.
AB  - Laboratory research has shown that numerous environmental pollutants cause
      mammary gland tumors in animals; are hormonally active, specifically mimicking
      estrogen, which is a breast cancer risk factor; or affect susceptibility of the
      mammary gland to carcinogenesis. An assessment of epidemiologic research on these
      pollutants identified in toxicologic studies can guide future research and
      exposure reduction aimed at prevention. The PubMed database was searched for
      relevant literature and systematic critical reviews were entered in a database
      available at URL: www.silentspring.org/sciencereview and URL:
      www.komen.org/environment (accessed April 10, 2007). Based on a relatively small
      number of studies, the evidence to date generally supports an association between
      breast cancer and polycyclic aromatic hydrocarbons (PAHs) and polychlorinated
      biphenyls (PCBs) in conjunction with certain genetic polymorphisms involved in
      carcinogen activation and steroid hormone metabolism. Evidence regarding dioxins
      and organic solvents is sparse and methodologically limited but suggestive of an
      association. Methodologic problems include inadequate exposure assessment, a lack
      of access to highly exposed and unexposed populations, and a lack of preclinical
      markers to identify associations that may be obscured by disease latency. Among
      chemicals identified in toxicologic research as relevant to breast cancer, many
      have not been investigated in humans. The development of better exposure
      assessment methods is needed to fill this gap. In the interim, weaknesses in the
      epidemiologic literature argue for greater reliance on toxicologic studies to
      develop national policies to reduce chemical exposures that may be associated
      with breast cancer. Substantial research progress in the last 5 years suggests
      that the investigation of environmental pollutants will lead to strategies to
      reduce breast cancer risk.

PMID- 17503437
TI  - Characterization of Ph-negative abnormal clones emerging during imatinib therapy.
AB  - BACKGROUND: Imatinib is a tyrosine kinase-specific inhibitor widely used for the
      treatment of chronic myeloid leukemia (CML). Studies reported the occurrence of
      additional cytogenetic abnormalities in the Philadelphia chromosome (Ph)-negative
      cell population emerging after treatment-induced suppression of the Ph-positive
      clone. These abnormalities were described in a relatively high proportion of
      patients treated with imatinib compared with the anecdotal reports of similar
      cases in patients treated with other drugs. However, the origin of these
      abnormalities as well as their biological and clinical significance are unknown.
      METHODS: The study involved 13 cases of patients diagnosed with CML carrying
      cytogenetic abnormalities in their Ph-negative cell population after imatinib
      treatment. The presence of the markers within the CD34+ stem cell compartment and
      the cell culture growth were analyzed and patients were followed over time.
      RESULTS: CD34+ cells express the cytogenetic markers present in Ph- cells,
      suggesting a possible involvement of the stem cell population. Cultured cells
      showed normal growth in all but 1 patient. No growth advantage was demonstrated
      for the Ph-negative or the Ph-positive clone after cell culture. CONCLUSIONS:
      After follow-up of up to 49 months, none of the patients had evolved to
      myelodysplasia or acute leukemia. Hypothesis regarding the biological and
      clinical significance of these abnormalities are formulated.

PMID- 17503439
TI  - Overexpression and gene amplification of BAG-1L in hormone-refractory prostate
      cancer.
AB  - BAG-1L (Bcl-2-associated anthanogene 1) has been found to interact with androgen
      receptor (AR), and has been suggested to be involved in the development of
      prostate cancer. In order to determine the presence of genetic and/or expression
      alterations of BAG-1L in prostate cancer, we analysed human prostate cancer cell
      lines and xenografts as well as patient samples of untreated, hormone-naive, and
      hormone-refractory prostate carcinomas for sequence variations using denaturing
      high-performance liquid chromatography (DHPLC), for gene copy number using
      fluorescence in situ hybridization (FISH), and for expression using both
      quantitative RT-PCR and immunostaining. Only one sequence variation was found in
      all 37 cell lines and xenografts analysed. BAG-1 gene amplification was detected
      in two xenografts. In addition, gene amplification was found in 6 of 81 (7.4%)
      hormone-refractory clinical tumours, whereas no amplification was found in any of
      the 130 untreated tumours analysed. Additionally, gain of the BAG-1 gene was
      observed in 27.2% of the hormone-refractory tumours and in 18.5% of the untreated
      carcinomas. In a set of 263 patient samples, BAG-1L protein expression was
      significantly higher in hormone-refractory tumours than in primary tumours (p =
      0.002). Altogether, these data suggest that amplification and overexpression of
      BAG-1L may be involved in the progression of prostate cancer.

PMID- 17503440
TI  - Measurement of cerebral perfusion territories using arterial spin labelling.
AB  - The ability to assess the perfusion territories of major cerebral arteries can be
      a valuable asset to the diagnosis of a number of cerebrovascular diseases.
      Recently, several arterial spin labeling (ASL) techniques have been proposed for
      determining the cerebral perfusion territories of individual arteries by three
      different approaches: (1) using a dedicated labeling radio frequency (RF) coil;
      (2) applying selective inversion of spatially confined areas; (3) employing
      multidimensional RF pulses. Methods that use a separate labeling RF coil have
      high signal-to-noise ratio (SNR), low RF power deposition, and unrestricted three
      dimensional coverage, but are mostly limited to separation of the left and right
      circulation, and do require extra hardware, which may limit their implementation
      in clinical systems. Alternatively, methods that utilize selective inversion have
      higher flexibility of implementation and higher arterial selectivity, but suffer
      from imaging artifacts resulting from interference between the labeling slab and
      the volume of interest. The goal of this review is to provide the reader with a
      critical survey of the different ASL approaches proposed to date for determining
      cerebral perfusion territories, by discussing the relative advantages and
      disadvantages of each technique, so as to serve as a guide for future refinement
      of this promising methodology.

PMID- 17503441
TI  - Magnetically enriched bone marrow-derived macrophages loaded in vitro with iron
      oxide can migrate to inflammation sites in mice.
AB  - In vitro labelling of cells permits incorporation of large amounts of iron oxide
      and consequently high detection sensitivity, but it remains controversial whether
      labelled cells would respond normally to stimuli. This question was addressed by
      differentiating bone marrow-derived macrophages (BMDMs) in vitro, labelling cells
      with high concentrations of Endorem in vitro, and eliminating unlabelled cells by
      magnetic enrichment. To explore their acute inflammatory response, enriched cells
      were injected into mice with carrageenan-induced inflammation, the 'air pouch
      model'. Cells recovered from the inflammation site 16 h after intravenous BMDM
      injection into the tail vein were analysed by in vitro MRI and fluorescent
      microscopy. With both assays, Endorem-labelled cells were detectable. This
      indicates that BMDMs, loaded with high concentrations of iron oxide in vitro, can
      still respond to chemokine gradients and infiltrate inflamed tissue in mice.
      Furthermore, by using genetically modified mice as BMDM donors, it should be
      possible to study the role of individual genes in macrophage recruitment.

PMID- 17503442
TI  - NG2-positive cells generate A2B5-positive oligodendrocyte precursor cells.
AB  - Cellular specification of the oligodendrocyte lineage occurs through a series of
      stages identified by expression of distinct biochemical characteristics. The best
      characterized oligodendrocyte progenitor cell (OPC) in vitro is the bipotential
      O2-A progenitor, identified by labeling with monoclonal antibody A2B5, which
      proliferates predominantly in response to platelet derived growth factor (PDGF).
      The cellular ancestors of O2-A progenitor cells are currently unclear. In vivo
      OPCs can be identified by expression of the cell surface markers NG2 (a sulfated
      proteoglycan) and platelet derived growth factor receptor alphaR). Substantial
      evidence supports the generation of oligodendrocytes from NG2(+), PDGFalphaR(+)
      cells both in vivo and in vitro. The developmental relationship between NG2(+)
      cells and A2B5(-) positive cells is unknown and it is unclear whether they
      represent identical, partially overlapping or nonoverlapping populations of
      cells. Here we show that in cultures of developing brain NG2(+) and A2B5(+) cells
      arise from overlapping cell populations. NG2(+) cells appear prior to the
      expression of A2B5(+) cells and generate A2B5(+) cells. We propose that during
      development NG2(+)/A2B5(-) cells (pre-OPCs) represent the direct ancestor to
      A2B5(+) O2A progenitor cells (OPCs).

PMID- 17503443
TI  - Advocate perspective: advancing science-based approaches to breast cancer
      prevention.

PMID- 17503444
TI  - Environmental pollutants, diet, physical activity, body size, and breast cancer:
      where do we stand in research to identify opportunities for prevention?
AB  - Breast cancer is the most common invasive cancer in women worldwide and the
      leading cause of death in US women in mid-life. Treatment has adverse effects,
      adding to the importance of finding modifiable risk factors. At the invitation of
      Susan G. Komen for the Cure, we reviewed studies of breast cancer and
      environmental pollutants, diet (assessed prospectively), body size, and physical
      activity, and animal studies that identify chemicals as potential mammary
      carcinogens. Databases developed in the review include information on 216
      chemicals that increased mammary gland tumors in animal studies and 450
      epidemiologic studies (accessible at www.silentspring.org/sciencereview and
      www.komen.org/environment). Exposure to potential mammary carcinogens is
      widespread from chemicals found in consumer products, air and drinking water
      pollution, food, and women's workplaces. Epidemiologic studies have included only
      a small number of chemicals identified as mammary carcinogens or as hormone
      disruptors, which may have implications for breast cancer; however, evidence is
      emerging for associations between breast cancer and polychlorinated biphenyls,
      polycyclic aromatic hydrocarbons, and organic solvents. Prospective diet studies
      have not revealed consistent associations with breast cancer. Improved exposure
      assessment methods will help advance future human studies of both diet and
      environmental pollutants. Studies of physical activity show that it is
      protective. In the same vein as evidence-based medicine, messages for patients,
      policymakers, and the public should support decision-making based on the strength
      of current evidence; such messages might address exposure reduction for some
      pollutants. Investments in research on environmental factors in breast cancer
      have potentially large public health benefits.

PMID- 17503445
TI  - Parallel effects of genetic variation in ACE activity in baboons and humans.
AB  - Like humans, savannah baboons (Papio sp.) show heritable interindividual
      variation in complex physiological phenotypes. One prominent example of such
      variation involves production of the homeostatic regulator protein angiotensin
      converting enzyme (ACE), which shows heritable variation in both baboons and
      humans. In humans, this phenotypic variation is associated with an Alu insertion
      deletion polymorphism in the ACE gene, which explains approximately half of the
      variation in serum ACE activity. We identified a similar Alu insertion-deletion
      polymorphism in the baboon ACE homologue and measured its frequency in a wild
      population and a captive population of baboons. We also analyzed the contribution
      of ACE genotype at this indel to variation in serum ACE activity in the captive
      population. When conditioned on weight, a known factor affecting ACE activity in
      humans, age and ACE genotype both accounted for variance in ACE activity; in
      particular, we identified a significant nonadditive interaction between age and
      genotype. A model incorporating this interaction effect explained 21.6% of the
      variation in residual serum ACE activity. Individuals homozygous for the deletion
      mutation exhibited significantly higher levels of ACE activity than insertion
      deletion heterozygotes at younger ages (10-14 years), but showed a trend towards
      lower levels of ACE activity compared with heterozygotes at older ages (> or =15
      years). These results demonstrate an interesting parallel between the genetic
      architecture underlying ACE variation in humans and baboons, suggesting that
      further attention should be paid in humans to the relationship between ACE
      genetic variation and aging.

PMID- 17503446
TI  - Technical note: compatibility of microtomographic imaging systems for dental
      measurements.
AB  - Modern micro-computed tomography techniques allow the accurate visualization of
      internal dental structures, and are becoming widely used within (paleo-)
      anthropological dental studies. There exist several types and name brands of
      microtomographic systems, however, which have been demonstrated to produce images
      that vary in resolution and signal-to-noise ratio. As a growing body of dental
      research using disparate microtomographic techniques is likely to continue
      accumulating, it is imperative that different systems are compared to ensure that
      results are comparable and not machine-dependent. In the present study, we
      compare volume, surface area, and linear measurements recorded on a sample of
      modern and fossil teeth using four microtomographic systems (three laboratory
      scanners, and the ID19 beamline of the European Synchrotron Radiation Facility).
      Results indicate that measurements are comparable between systems (within 3%),
      but that synchrotron radiation is superior to the other systems because its
      monochromatic X-rays prevent beam hardening and its parallel beam prevents
      geometric artifacts in the resultant images, making it easier to record
      measurements and see fine details at the enamel cervix or dentine horn tips.
      Although the synchrotron produces higher resolution images with less artifacts,
      results indicate that for gross morphological measurements (e.g., enamel cap
      volume, intercuspal distances), each of the scanners produces approximately the
      same measurements. Combining measurements of teeth from multiple microCT systems
      presupposes that measurements from each system are comparable; the research
      presented here indicates that this is the case when teeth are not severely
      diagenetically remineralized.

PMID- 17503447
TI  - Robusticity and sexual dimorphism in the postcranium of modern hunter-gatherers
      from Australia.
AB  - Throughout much of prehistory, humans practiced a hunting and gathering
      subsistence strategy. Elevated postcranial robusticity and sexually dimorphic
      mobility patterns are presumed consequences of this strategy, in which males are
      attributed greater robusticity and mobility than females. Much of the basis for
      these trends originates from populations where skeletal correlates of activity
      patterns are known (e.g., cross-sectional geometric properties of long bones),
      but in which activity patterns are inferred using evidence such as archaeological
      records (e.g., Pleistocene Europe). Australian hunter-gatherers provide an
      opportunity to critically assess these ideas since ethnographic documentation of
      their activity patterns is available. We address the following questions: do
      skeletal indicators of Australian hunter-gatherers express elevated postcranial
      robusticity and sexually dimorphic mobility relative to populations from similar
      latitudes, and do ethnographic accounts support these findings. Using computed
      tomography, cross-sectional images were obtained from 149 skeletal elements
      including humeri, radii, ulnae, femora, and tibiae. Cross-sectional geometric
      properties were calculated from image data and standardized for body size.
      Australian hunter-gatherers often have reduced robusticity at femoral and humeral
      midshafts relative to forager (Khoi-San), agricultural/industrialized (Zulu), and
      industrialized (African American) groups. Australian hunter-gatherers display
      more sexual dimorphism in upper limb robusticity than lower limb robusticity.
      Attributing specific behavioral causes to upper limb sexual dimorphism is
      premature, although ethnographic accounts support sex-specific differences in
      tool use. Virtually absent sexual dimorphism in lower limb robusticity is
      consistent with ethnographic accounts of equivalently high mobility among females
      and males. Thus, elevated postcranial robusticity and sexually dimorphic mobility
      do not always characterize hunter-gatherers.

PMID- 17503448
TI  - The problem of assessing landmark error in geometric morphometrics: theory,
      methods, and modifications.
AB  - Geometric morphometric methods rely on the accurate identification and
      quantification of landmarks on biological specimens. As in any empirical
      analysis, the assessment of inter- and intra-observer error is desirable. A
      review of methods currently being employed to assess measurement error in
      geometric morphometrics was conducted and three general approaches to the problem
      were identified. One such approach employs Generalized Procrustes Analysis to
      superimpose repeatedly digitized landmark configurations, thereby establishing
      whether repeat measures fall within an acceptable range of variation. The
      potential problem of this error assessment method (the "Pinocchio effect") is
      demonstrated and its effect on error studies discussed. An alternative approach
      involves employing Euclidean distances between the configuration centroid and
      repeat measures of a landmark to assess the relative repeatability of individual
      landmarks. This method is also potentially problematic as the inherent geometric
      properties of the specimen can result in misleading estimates of measurement
      error. A third approach involved the repeated digitization of landmarks with the
      specimen held in a constant orientation to assess individual landmark precision.
      This latter approach is an ideal method for assessing individual landmark
      precision, but is restrictive in that it does not allow for the incorporation of
      instrumentally defined or Type III landmarks. Hence, a revised method for
      assessing landmark error is proposed and described with the aid of worked
      empirical examples.

PMID- 17503449
TI  - Thoracic skeletal morphology and high-altitude hypoxia in Andean prehistory.
AB  - Living humans from the highland Andes exhibit antero-posteriorly and medio
      laterally enlarged chests in response to high-altitude hypoxia. This study
      hypothesizes that morphological responses to high-altitude hypoxia should also be
      evident in pre-Contact Andean groups. Thoracic skeletal morphology in four groups
      of human skeletons (N = 347) are compared: two groups from coastal regions
      (Ancon, Peru, n = 79 and Arica, Chile, n = 123) and two groups from high
      altitudes (San Pedro de Atacama, Chile, n = 102 and Machu Picchu and Cuzco, Peru,
      n = 43). Osteometric variables that represent proportions of chest width and
      depth include sternal and clavicular lengths and breadths and rib length,
      curvature, and area. Each variable was measured relative to body size,
      transformed into logarithmic indices, and compared across sex-specific groups
      using ANOVA and Tukey multiple comparison tests. Atacama highlanders have the
      largest sternal and clavicular proportions and ribs with the greatest area and
      least amount of curvature, features that suggest an antero-posteriorly deep and
      mediolaterally wide thoracic skeleton. Ancon lowlanders exhibit proportions
      indicating narrower and shallower chests. Machu Picchu and Cuzco males cluster
      with the other highland group in rib curvature and area at the superior levels of
      the thorax, whereas chest proportions in Machu Picchu and Cuzco females resemble
      those of lowlanders. The variation in Machu Picchu and Cuzco males and females is
      interpreted as the result of population migrations. The presence of morphological
      traits indicative of enlarged chests in some highland individuals suggests that
      high-altitude hypoxia was an environmental stressor shaping the biology of
      highland Andean groups during the pre-Contact period.

PMID- 17503450
TI  - Functional morphology of the mangabey mandibular corpus: relationship to dental
      specializations and feeding behavior.
AB  - Recent molecular and morphological surveys suggest that mangabeys do not
      represent a monophyletic group. Specifically, Cercocebus is the sister taxon of
      Mandrillus, whereas Lophocebus forms an unresolved trichotomy with Papio and
      Theropithecus. The Cercocebus-Mandrillus clade is characterized by skeletal and
      dental adaptations related to acquisition and processing of hard-object foods
      that resist decomposition for months on the forest floor. Although species of
      both mangabey genera can be described as frugivorous seed predators with a strong
      reliance on hard-object foods, a growing body of evidence indicates that
      Cercocebus (terrestrial) and Lophocebus (arboreal) mangabeys differ in the
      hardness of the seeds they consume and the manner in which seeds are processed.
      The taxa are also distinguished on the basis of dental morphology. Given the
      purported differences in feeding behaviors of the two mangabey genera, we
      consider whether there are predictable biomechanical consequences of these
      behaviors that are reflected in mandibular corpus dimensions. In addition, we
      present metric data summarizing functional aspects of mangabey mandibular corpus
      morphology. Mangabey genera are generally not distinguished by differences in
      relative corpus size, either in postcanine or symphyseal regions. Distinct
      symphyseal scaling patterns characterize the Papio-Lophocebus clade and the
      Mandrillus-Cercocebus clade, while the postcanine corpus scales similarly between
      them. The hypothesis that preferential use of the incisors vs. premolars to
      initially process these foods results in distinct stress environments is weakly
      supported, given circumstantial evidence that the relative importance of bending
      vs. torsion may differ between Cercocebus and Lophocebus.

PMID- 17503451
TI  - Family-based association study of neuregulin-1 gene and psychosis in a Spanish
      sample.
AB  - Neuregulin 1 (NRG1) is one of the most exciting candidate genes for schizophrenia
      since its first association with the disorder in an Icelandic population. Since
      then, many studies have analyzed allele and haplotype frequencies in European and
      Asian populations in cases and controls yielding varying results. We investigated
      the association of NRG1 with psychosis in a total sample set of 575 individuals
      from 151 Spanish nuclear families. We tested eight SNPs across 1.2 Mb along NRG1
      including regions previously associated to schizophrenia in association studies.
      After correction for multiple testing, the TDT analysis for each marker did not
      show a significant over-transmission of alleles from the parents to the affected
      offspring for any of the markers (P > 0.05). The haplotypic analysis with
      TRANSMIT and PDT did not show preferential transmission for any of the haplotypes
      analyzed in our sample. These results do not seem to suggest that the
      investigated NRG1 markers play a role in schizophrenia in the Spanish population,
      although the finding of a trend for association with one SNP in the 3'of the gene
      warrants further investigation.

PMID- 17503452
TI  - Spastic paraplegia 5: Locus refinement, candidate gene analysis and clinical
      description.
AB  - Thirty-three different loci for hereditary spastic paraplegias (HSP) have been
      mapped, and 15 responsible genes have been identified. Autosomal recessive
      spastic paraplegias (ARHSPs) usually have clinically complex phenotypes but the
      SPG5, SPG24, and SPG28 loci are considered to be associated with pure forms of
      the disease. We performed a genome-wide scan in a large French family. Fine
      mapping of the refined SPG5 region on chromosome 8q12 was performed in another 17
      ARHSP families with additional microsatellite markers. After exclusion of known
      ARHSP loci, the genome-wide screen provided evidence of linkage with a maximal
      multipoint lod score of 2.6 in the D8S1113-D8S1699 interval. This interval
      partially overlapped SPG5 and reduced it to a 5.9 megabase (Mb)-region between
      D8S1113 and D8S544. In a family of Algerian origin from a series of 17 other
      ARHSP kindreds, linkage to the SPG5 locus was supported by a multipoint lod score
      of 2.3. The direct sequencing of the coding exons of seven candidate genes did
      not detect mutations/polymorphisms in the index cases of both linked families.
      The phenotype of the two SPG5-linked families consisted of spastic paraparesis
      associated with deep sensory loss. In several patients with long disease
      durations, there were also mild cerebellar signs. The frequency of SPG5 was
      approximately 10% (2/18) in our series of ARHSP families with pure or complex
      forms. We have refined the SPG5 locus to a 3.8 cM interval and extended the
      phenotype of this form of ARHSP to include slight cerebellar signs.

PMID- 17503453
TI  - Contribution of the anterior thalamic nuclei to conditional learning in rats.
AB  - The anterior thalamic region is intimately linked anatomically and functionally
      with the hippocampus, which is critical for various forms of spatial learning.
      Rats with lesions to the anterior thalamic nuclei and a control group were
      trained on a visual-spatial conditional associative learning task in which they
      had to learn to go to one of two locations depending on the particular visual cue
      presented on each trial; the rats approached the cues from different directions.
      The animals were subsequently tested on a spatial working memory task, the eight
      arm radial maze. Performance on both these tasks had previously been shown to be
      impaired by hippocampal lesions. Rats with anterior thalamic damage were able to
      acquire the conditional associative task at a rate comparable to that of the
      control animals, but were impaired on the radial maze task. The finding of a
      dissociation between the effects of lesions of the anterior thalamic nuclei on
      two different classes of behavior known to be associated with hippocampal
      function suggest that while different neural stations within the extended
      hippocampal circuit may all play a role in spatial learning, the role of each of
      these regions in such learning may be more selective than previously considered.

PMID- 17503454
TI  - Analysis of Kupffer's vesicle in zebrafish embryos using a cave automated virtual
      environment.
AB  - Previous studies show that cilia in Kupffer's vesicle (KV) generate a
      counterclockwise flow of fluid and provide convincing evidence that this flow
      regulates left/right asymmetry. We hypothesized that the distribution of cilia in
      KV leads to this directional flow. However, there are limitations in determining
      the localization of structures when viewing a three-dimensional (3-D) image on a
      2-D computer screen. We analyzed the distribution of KV cilia in the Cave, an
      immersive virtual environment that displays stacks of confocal images in 3-D. We
      found 80% of the cilia are located on the dorsal surface and 20% were located on
      the ventral surface of the vesicle. We confirmed the ventral location of some
      cilia by electron microscopy. There is an asymmetrical distribution of cilia on
      the dorsal surface, with the anterior one third containing 50% and the posterior
      one third containing 20% of the cilia. This dorsal-anterior patch could explain
      the directionality of the flow, and could drive local differences in flow rate.

PMID- 17503455
TI  - Laminins in the developing and adult human small intestine: relation with the
      functional absorptive unit.
AB  - The expression of the five laminin alpha-chains was analyzed in the developing
      and mature human small intestine at the protein and transcript levels in order to
      further delineate specific involvement of individual laminins in relation to the
      epithelial cell state as defined along the functional crypt-villus axis. The
      results show that all of the alpha-laminin transcripts are expressed in
      significant amounts in the small intestine relative to a panel of other tissues
      and organs. Further analysis of their expression by indirect immunofluorescence
      and semi-quantitative and quantitative RT-PCR demonstrates a close correlation
      between transcript and protein expression, distinct epithelial and mesenchymal
      origins, as well as differential occurrence in intestinal basement membranes
      according to developmental stage, along the crypt-villus axis and in compartment
      related experimental intestinal cell models. Taken together, the data point out
      the prime importance of alpha2-, alpha3-, and alpha5-containing laminins for the
      development and maintenance of the functional human intestinal epithelium.

PMID- 17503456
TI  - Systematic study of the boundary composition in Poisson Boltzmann calculations.
AB  - We describe a three-stage procedure to analyze the dependence of Poisson
      Boltzmann calculations on the shape, size and geometry of the boundary between
      solute and solvent. Our study is carried out within the boundary element
      formalism, but our results are also of interest to finite difference techniques
      of Poisson Boltzmann calculations. At first, we identify the critical size of the
      geometrical elements for discretizing the boundary, and thus the necessary
      resolution required to establish numerical convergence. In the following two
      steps we perform reference calculations on a set of dipeptides in different
      conformations using the Polarizable Continuum Model and a high-level Density
      Functional as well as a high-quality basis set. Afterwards, we propose a
      mechanism for defining appropriate boundary geometries. Finally, we compare the
      classic Poisson Boltzmann description with the Quantum Chemical description, and
      aim at finding appropriate fitting parameters to get a close match to the
      reference data. Surprisingly, when using default AMBER partial charges and the
      rigorous geometric parameters derived in the initial two stages, no scaling of
      the partial charges is necessary and the best fit against the reference set is
      obtained automatically.

PMID- 17503457
TI  - A hierarchic sparse matrix data structure for large-scale Hartree-Fock/Kohn-Sham
      calculations.
AB  - A hierarchic sparse matrix data structure for Hartree-Fock/Kohn-Sham calculations
      is presented. The data structure makes the implementation of matrix manipulations
      needed for large systems faster, easier, and more maintainable without loss of
      performance. Algorithms for symmetric matrix square and inverse Cholesky
      decomposition within the hierarchic framework are also described. The presented
      data structure is general; in addition to its use in Hartree-Fock/Kohn-Sham
      calculations, it may also be used in other research areas where matrices with
      similar properties are encountered. The applicability of the data structure to ab
      initio calculations is shown with help of benchmarks on water droplets and
      graphene nanoribbons.

PMID- 17503458
TI  - The health behaviors of the older US worker.
AB  - BACKGROUND: As the US workforce ages, lifestyle factors will increasingly affect
      their health, yet little information is available on their prevalence in older
      working populations. METHODS: Using the nationally representative 1997-2003
      National Health Interview Survey (NHIS), reported current smoking, risky drinking
      and leisure-time physical activity behaviors of older workers (> or =65 years)
      were compared with older non-workers. These behaviors were evaluated by age,
      gender, race, ethnicity, and occupation, as well as prototype "healthy" and
      "risky" persons. RESULTS: The study population of 4,946 older US workers and
      38,313 older non-workers represented an estimated 3.9 million older workers and
      28.9 million older non-workers annually. Relative to older non-workers, older
      workers reported more current smoking and risky drinking, but higher levels of
      leisure-time physical activity with variations by subpopulations. CONCLUSIONS:
      Less than 4% of the older US worker population reported overall healthy
      behaviors. Certain occupations and other subpopulations can be targeted for age
      appropriate behavioral interventions.

PMID- 17503459
TI  - Chromatin compaction and cell death by high molecular weight FGF-2 depend on its
      nuclear localization, intracrine ERK activation, and engagement of mitochondria.
AB  - Fibroblast growth factor 2 (FGF-2) is produced as CUG-initiated, 22-34 kDa or AUG
      initiated 18 kDa isoforms (hi- and lo-FGF-2, respectively), with potentially
      distinct functions. We report that expression of hi-FGF-2 in HEK293 cells
      elicited chromatin compaction preceding cell death with apoptotic features.
      Nuclear localization of the intact protein was required as expression of a non
      nuclear hi-FGF-2 mutant failed to elicit chromatin compaction. Equally
      ineffective, despite nuclear localization, was the over-expression of the 18 kDa
      core sequence (lo-FGF-2). Chromatin compaction by hi-FGF-2 was accompanied by
      increased cytosolic cytochrome C, and was attenuated either by over-expression of
      Bcl-2 or by a peptide inhibitor of the pro-apoptotic protein Bax. In addition hi
      FGF-2 elicited sustained activation of total and nuclear extracellular signal
      regulated kinase (ERK1/2) by an intracrine route, as it was not prevented by
      neutralizing anti-FGF-2 antibodies. Inhibition of the ERK1/2 activating pathway
      by dominant negative upstream activating kinase, or by PD 98059, prevented
      chromatin compaction by hi-FGF-2. ERK1/2 activation was not affected by the Bax
      inhibiting peptide suggesting that it occurred upstream of mitochondrial
      involvement. We conclude that the hi-FGF-2-induced chromatin compaction and cell
      death requires its nuclear localization, intracrine ERK1/2 activation and
      mitochondrial engagement.

PMID- 17503465
TI  - Tyrosine-phosphorylated STAT5 accumulates on podosomes in Hck-transformed
      fibroblasts and chronic myeloid leukemia cells.
AB  - In chronic myeloid leukemia (CML), the transforming activity of Bcr/Abl involves
      constitutive activation of the phagocyte specific Src-family tyrosine kinase Hck,
      which in turn directly activates the signal transducer and activator of
      transcription 5 (STAT5). The effect of Hck on STAT5 was first explored
      independently of Bcr/Abl by expressing the constitutively active Hck mutant
      (Hck(ca)) in MEF3T3-TetOff fibroblasts. As previously reported, Hck(ca)
      expressing cells form podosomes which are actin-rich structures involved in trans
      tissular cell migration and found in the few cell types able to cross anatomic
      boundaries. We demonstrated that in these cells, the tyrosine-phosphorylated form
      of STAT5 (PY-STAT5) increased and preferentially localized on podosomes together
      with Hck, instead of translocating to the nucleus as observed with conventional
      stimuli such as IFNgamma. To examine whether similar results were obtained in the
      presence of Bcr/Abl, the CML cell line K562 was used. We observed that (i)
      podosomal structures are present in these cells in contrast to Bcr/Abl-negative
      leukemic cells, (ii) podosome formation was inhibited by Bcr/Abl- and Src-kinase
      inhibitors, and (iii) PY-STAT5 mainly colocalized with Hck on these structures.
      The presence of podosomes was not sufficient to trap STAT5 since in normal
      macrophages which spontaneously form podosomes and express regulated Hck, PY
      STAT5 is in the nucleus. In conclusion, this is the first report showing that PY
      STAT5 associates to podosomes in a process dependent on constitutive activation
      of Hck. We propose that STAT5, previously classified as a transcription factor,
      could play another role outside the nucleus, elicited by the Bcr/Abl-Hck
      transforming pathway.

PMID- 17503466
TI  - An N-terminal nucleotide-binding site in VDAC1: involvement in regulating
      mitochondrial function.
AB  - In a previous study, we presented evidence for the existence of a nucleotide
      binding site (NBS) in the N-terminal region of the voltage-dependent anion
      channel (VDAC1). In this study, further localization and possible roles of the
      proposed VDAC1-NBS were investigated using site-directed mutagenesis. The
      predicated NBS of murine VDAC1 (mVDAC1) was mutated by replacing two glycine
      residues with alanines or a conserved lysine residue with a serine. Expression of
      the G21A,G23A- and K20S-mVDAC1s in human T-REx-293 cells in which endogenous
      VDAC1 expression had been silenced affected cell growth and cytosolic ATP levels.
      While G21A,G23A-mVDAC1-expressing cells displayed growth rates similar to native
      mVDAC1-expressing cells, the K20S-mVDAC1-expressing cells displayed significantly
      retarded growth and increased resistance to cell death. Cells expressing either
      mVDAC1 mutant also displayed significantly reduced cellular ATP levels. When K20S
      mutant mVDAC1 was expressed in porin1-less yeast, the transformed cells grew
      slower on non-fermentable carbon sources, while isolated mitochondria expressing
      either mVDAC1 mutant showed significant reduction in ATP synthesis. Purified K20S
      mVDAC1 displayed a significant decrease in [alpha-(32)P]BzATP-binding and altered
      channel properties, that is, reduced ion selectivity, while the G21A,G23A-mutant
      protein displayed only a mild reduction in channel selectivity. These results
      suggest that mutations in the proposed VDAC1-NBS, particularly the K20S, altered
      channel activity, thereby interfering with VDAC function as the major pathway for
      the transport of metabolites and adenine nucleotides across the outer
      mitochondrial membrane. Finally, involvement of the VDAC1-NBS in the control of
      mitochondrial ATP synthesis, cell growth and viability is discussed.

PMID- 17503467
TI  - The PVT-1 oncogene is a Myc protein target that is overexpressed in transformed
      cells.
AB  - The human PVT-1 gene is located on chromosome 8 telomeric to the c-Myc gene and
      it is frequently involved in the translocations occurring in variant Burkitt's
      lymphomas and murine plasmacytomas. It has been proposed that PVT-1 regulates c
      Myc gene transcription over a long distance. To get new insights into the
      functional relationships between the two genes, we have investigated PVT-1 and c
      Myc expression in normal human tissues and in transformed cells. Our findings
      indicate that PVT-1 expression is restricted to a relative low number of normal
      tissues compared to the wide distribution of c-Myc mRNA, whereas the gene is
      highly expressed in many transformed cell types including neuroblastoma cells
      that do not express c-Myc. Reporter gene assays were used to dissect the PVT-1
      promoter and to identify the region responsible for the elevated expression
      observed in transformed cells. This region contains two putative binding sites
      for Myc proteins. The results of transfection experiments in RAT1-MycER cells and
      chromatin immunoprecipitation (ChIP) assays in proliferating and differentiated
      neuroblastoma cells indicate that PVT-1 is a downstream target of Myc proteins.

PMID- 17503468
TI  - Endosulfan decreases cell growth and apoptosis in human HaCaT keratinocytes:
      partial ROS-dependent ERK1/2 mechanism.
AB  - Endosulfan is an organochlorine insecticide described as a potential carcinogen
      in humans. This insecticide was recently reported to alter the mitogen-activated
      protein (MAP) kinase signaling pathways and is suspected to affect cell growth
      and differentiation in human keratinocytes. This study was designed to assess the
      mitogenic, apoptogenic, and genotoxic effects of endosulfan on the HaCaT cell
      line. We first found that 25 microM endosulfan led to persistent extracellular
      signal-regulated kinase (ERK)1/2 phosphorylation with an accumulation of the
      phosphorylated form in the nucleus, probably caused by MAP kinase phosphatase
      (MKP) inhibition. As previously described under sustained ERK1/2 activation, cell
      growth was decreased: delayed confluency and 35% decrease of BrdU incorporation
      was demonstrated in endosulfan-treated keratinocytes. In addition, endosulfan has
      been shown to generate transient reactive oxygen species (ROS), and blocking this
      oxidative stress by N-acetyl cysteine (NAC) strongly prevented both persistent
      nuclear ERK1/2 phosphorylation and cell growth decrease. Additional experiments
      demonstrated that unchanged endosulfan rather than its metabolites has mutagenic
      effects (Ames positive without S9) and increased DNA strand breaks (Comet assay)
      in HaCaT cells, via a ROS-dependent mechanism. Therefore, to assess the putative
      pro-apoptotic response of damaged cells, caspases 3/7 activity and poly(ADP
      ribose)-polymerase (PARP) cleavage were measured. The results clearly indicated
      that endosulfan inhibited both spontaneous and staurosporine-induced apoptosis.
      Taken together, these findings strongly support that endosulfan induces ROS
      generation leading to sustained ERK1/2 phosphorylation and decrease in cell
      growth. Moreover, endosulfan was found to inhibit apoptosis and this could
      contribute to mutant cell survival and therefore have possible carcinogenic
      effects.

PMID- 17503469
TI  - Androgen receptor or estrogen receptor-beta blockade alters DHEA-, DHT-, and E(2)
      induced proliferation and PSA production in human prostate cancer cells.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) is an endogenous steroid that is
      metabolized to androgens and/or estrogens in the human prostate. DHEA levels
      decline with age, and use of DHEA supplements to retard the aging process is of
      unproved effectiveness and safety. LNCaP and LAPC-4 prostate cancer cells were
      used to determine whether DHEA-modulated proliferation and prostate specific
      antigen (PSA) production were mediated via the androgen receptor (AR) and/or
      ERbeta. METHODS: Cells were treated with DHEA, DHT, or E(2) and antagonists to AR
      (Casodex-bicalutamide) or ER (ICI 182,780) or siRNA to the respective receptors.
      Proliferation was assessed by MTT assay and PSA mRNA and protein secretion were
      measured by quantitative real-time PCR and ELISA. Associations of AR and ERbeta
      were analyzed by co-immunoprecipitation studies and fluorescent confocal
      microscopy. RESULTS: DHEA-, T-, and E(2)-induced proliferation of LNCaP cells was
      blunted by Casodex but not by ICI treatment. In LNCaP cells, Casodex and ICI
      suppressed hormone-induced PSA production. In LAPC-4 cells, DHT-stimulated PSA
      mRNA was inhibited by Casodex and ICI, and the minimal stimulation by DHEA was
      inhibited by ICI. Use of siRNAs confirmed involvement of AR and ERbeta in hormone
      induced PSA production while AR-ERbeta co-association was suggested by
      immunoprecipitation and nuclear co-localization. CONCLUSIONS: These findings
      support involvement of both AR and ERbeta in mediating DHEA-, DHT-, and E(2)
      induced PSA expression in prostate cancer cells.

PMID- 17503470
TI  - Anatomical and pharmacological relationship between acetylcholine and nitric
      oxide in the prepositus hypoglossi nucleus of the cat: functional implications
      for eye-movement control.
AB  - The prepositus hypoglossi (PH) nucleus has been proposed as a pivotal structure
      for horizontal eye-position generation in the oculomotor system. Recent studies
      have revealed that acetylcholine (ACh) in the PH nucleus could mediate the
      persistent activity necessary for this process, although the origin of this ACh
      remains unknown. It is also known that nitric oxide (NO) in the PH nucleus plays
      an important role in the control of velocity balance, being involved in a
      negative feedback control of tonic signals arriving at the PH nucleus. As it
      could be expected that neurons taking part in eye-position generation must
      control their tonic background inputs, the existence of a relationship between
      nitrergic and cholinergic neurons is hypothesized. In the present study we
      analyzed the distribution, size, and morphology of choline acetyltransferase
      positive neurons, and their relationship with neuronal nitric oxide synthase in
      the PH nucleus of the cat. As presumed, some 96% of cholinergic neurons were also
      nitrergic in the PH nucleus, suggesting that NO is regulating the level of ACh
      released by cholinergic PH neurons. Furthermore, we studied the alterations
      induced by muscarinic-receptor agonists and antagonists on spontaneous and
      vestibularly induced eye movements in the alert cat and compared them with those
      induced in previous studies by modification of NO levels in the same animal
      preparation. The results suggest that ACh is necessary for the generation of
      saccadic and vestibular eye-position signals, whereas the NO is stabilizing the
      eye-position generator by controlling background activity reaching cholinergic
      neurons in the PH nucleus.

PMID- 17503471
TI  - Prostate stem cell antigen (PSCA) mRNA expression in prostatic intraepithelial
      neoplasia: implications for the development of prostate cancer.
AB  - BACKGROUND: Prior data clearly demonstrated the expression of prostate stem cell
      antigen (PSCA) mRNA in prostatic intraepithelial neoplasia (PIN) tissues. The
      purpose of the present investigation was to determine whether PSCA mRNA
      expression was associated with the presence of cancer in this disease. METHODS:
      One hundred seventeen men were diagnosed with isolated PIN on initial prostate
      biopsy, 51 with low-grade form (LGPIN), and 66 with high-grade form (HGPIN). PSCA
      mRNA expression in initial PIN and subsequent cancer was examined by in situ
      hybridization (ISH). The differences of the PSCA mRNA expression level between
      the groups were analyzed by the Chi-square and Student's t-test. Univariate and
      multivariate logistic regression analyses were performed to evaluate the
      predictive performance of PSCA mRNA. RESULTS: PSCA mRNA expression level in 34
      subsequent cancers was statistically increased compared with their paired PIN (P
      < 0.001), with a Gleason's dependence. HGPIN showed statistically high PSCA mRNA
      expression compared with LGPIN (P < 0.01). PSCA mRNA expression levels were
      significantly stronger in the initial isolated LGPIN and isolated HGPIN with
      subsequent cancer than those without (P < 0.001 and P < 0.001, respectively).
      Multivariate logistic regression analysis demonstrated that only PSCA mRNA was
      predictive of the onset of subsequent cancer in patients with isolated LGPIN and
      in those with isolated HGPIN, respectively. CONCLUSIONS: Our data identify PSCA
      mRNA in initial PIN as a significant predictor of subsequent cancer, suggesting
      that PSCA implies in prostatic tumorigenesis and may be used to identify the
      patients with isolated PIN who are at high risk for cancer onset in the disease
      process.

PMID- 17503472
TI  - Dopamine beta-hydroxylase gene polymorphisms and psychotic symptoms in
      schizophrenia.

PMID- 17503473
TI  - No evidence for a preferential transmission of the methylenetetrahydrofolate
      reductase 677T allele in families with schizophrenia offspring.
AB  - The methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism has been
      associated with an increased risk of schizophrenia in various case-control
      studies. However, case-control studies are sensitive to population
      stratification, which is not an issue in family-based studies. We conducted a
      family-based study comprising 120 families with a schizophrenic family member to
      explore the association between the parental MTHFR 677C > T polymorphism and
      schizophrenia risk in offspring. In addition, a meta-analysis was performed using
      the available studies with data on this subject. Transmission Disequilibrium Test
      (TDT) analysis showed no preferential transmission of the 677T allele from
      parents heterozygous for the MTHFR 677C > T polymorphism to schizophrenia
      offspring (P = 0.27). The genotype relative risks were 1.43 (95% CI: 0.83-2.47)
      for the 677TT and 1.42 (95% CI: 0.54-3.78) for the 677CT genotype, relative to
      the 677CC genotype. A meta-analysis using data from family-based studies
      comprising a total of 416 parent-child triads yielded no evidence implicating the
      677T allele in schizophrenia risk (P = 0.58). By applying a log-linear model, we
      found no asymmetry within parental mating type. Our data provided no evidence
      that transmission of the MTHFR 677T allele is associated with schizophrenia risk.
      In addition, we found no evidence that the maternal genotype influences the risk
      of having schizophrenia offspring substantially.

PMID- 17503474
TI  - Cytogenetic and molecular characterization of A2BP1/FOX1 as a candidate gene for
      autism.
AB  - Cytogenetic imbalances are increasingly being realized as causes of autism. Here,
      we report a de novo translocation between the short arms of chromosomes 15 and 16
      in a female with autism, epilepsy, and global developmental delay. FISH analysis
      identified a cryptic deletion of approximately 160 kb at the boundary of the
      first exon and first intron of the 1.7 Mb ataxin-2 binding protein-1 (A2BP1)
      gene, also called FOX1. Quantitative real time PCR (Q-PCR) analysis verified a
      deletion of exon 1 in the 5' promoter region of the A2BP1 gene. Reverse
      transcription PCR (qRT-PCR) showed reduced mRNA expression in the individual's
      lymphocytes, demonstrating the functional consequence of the deletion. A2BP1
      codes for a brain-expressed RNA binding or splicing factor. Because of emerging
      evidence in the role of RNA processing and gene regulation in pervasive
      developmental disorders, we performed further screening of A2BP1 in additional
      individuals with autism from the Autism Genetics Resource Exchange (AGRE)
      collection. Twenty-seven SNPs were genotyped across A2BP1 in 206 parent-child
      trios and two regions showed association at P < or = 0.008 level. No additional
      deletions or clear mutations were identified in 88 probands by re-sequencing of
      all exons and surrounding intronic regions or quantitative PCR (Q-PCR) of exon 1.
      Although only nominal association was observed, and no obvious causal mutations
      were identified, these results suggest that A2BP1 may affect susceptibility or
      cause autism in a subset of patients. Further investigations in a larger sample
      may provide additional information regarding the involvement of this gene in the
      autistic phenotype.

PMID- 17503475
TI  - Alzheimer's disease: case-control association study of polymorphisms in ACHE,
      CHAT, and BCHE genes in a Sardinian sample.
AB  - Alzheimer's disease (AD) is characterized by an extensive loss of cholinergic
      neurons, and their cortical projections, from the basal forebrain area. The
      resulting reduction in cholinergic activity is associated with decreased levels
      of the neurotransmitter acetylcholine (ACh), decreased activity of
      acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and increased
      butyrylcholinesterase (BChE) activity. In the present study, we investigated
      whether the BCHE, ACHE, and CHAT genes were associated with AD and the
      possibility of a synergistic effect with APOE-epsilon4 in a Sardinian sample. AD
      patients (n = 158), exclusively of Sardinian ancestry, were recruited from the
      Division of Geriatrics Local Health Agency 8 and Unit of Clinical Pharmacology,
      Department of Neurosciences, University of Cagliari. Patients were diagnosed
      according to DSM-IV, and National Institute of Neurologic and Communicative
      Disorders and Stroke-AD and Related Disorders Association (NINCDS-ADRDA) criteria
      for possible or probable AD. Cognitive screening was performed by means of Mini
      Mental State Examination (MMSE). Healthy controls (n = 118) of Sardinian ancestry
      were recruited from religious and sport associations. All patients and control
      subjects gave informed consent for participation in the study. Single nucleotide
      polymorphism (SNP) analysis was performed by PCR/RFLP or the TaqMan 5'
      exonuclease method. Our study confirms the association between APOE epsilon4
      allele and AD (P < 0.000). No significant differences were observed in allele and
      genotype frequencies of BCHE, ACHE, and CHAT between AD and controls. Haplotype
      analysis of ACHE SNPs did not reveal a significant association between ACHE and
      AD. Our results suggest that the AChE, ChAT, and BChE polymorphisms do not
      constitute a major genetic risk factor for susceptibility to AD in a Sardinian
      population.

PMID- 17503476
TI  - Porcine maternal infanticide as a model for puerperal psychosis.
AB  - Childbirth is a period of substantial rapid biological and psychological change
      and a wide range of psychotic disorders can occur ranging from mild 'baby blues'
      to severe episodes of psychotic illnesses. Puerperal psychosis is the most
      extreme form of postnatal psychosis, occurring in 1 in 1,000 births. In this
      study, we have used the pig as an animal model for human postnatal psychiatric
      illness. Our aim was to identify quantitative trait loci (QTL) associated with
      maternal (infanticide) sow aggression. This is defined by sows attacking and
      killing their own newborn offspring, within 24 hr of birth. An affected sib pair
      whole genome linkage analysis was carried out with 80 microsatellite markers
      covering the 18 porcine autosomes and the X chromosome, with the aim of
      identifying chromosomal regions responsible for this abnormal behavior. Analysis
      was carried out using the non-parametric linkage test of Whittemore and Halpern,
      as implemented in the Merlin software. The results identified 4 QTL mapping on
      Sus scrofa chromosomes 2 (SSC2), 10 (SSC10), and X (SSCX). The peak regions of
      these QTL are syntenic to HSA 5q14.3-15, 1q32, Xpter-Xp2.1, and Xq2.4-Xqter,
      respectively. Several potential candidate genes lie in these regions in addition
      to relevant abnormal behavioral QTL, found in humans and rodents.

PMID- 17503477
TI  - A subgroup of Tourette's patients overexpress specific natural killer cell genes
      in blood: a preliminary report.
AB  - Gilles de la Tourette Syndrome (TS) is a heritable, neurodevelopmental disorder
      characterized by motor and vocal tics. As no single gene or region has emerged
      from standard linkage approaches, TS may result from several as-yet-unidentified
      genetic factors, and may also occur due to infection-triggered, autoimmune
      processes. Etiological or pathogenic differences might result in clinically
      indistinguishable TS subgroups. We have previously used whole genome human
      oligonucleotide microarrays in an attempt to identify patterns of gene expression
      in blood linked with TS. In this proof-of-principle study, we applied Principal
      Components Analysis to a previously collected set of 16 familial TS and 16
      control blood samples to identify subgroups. Fourteen genes, primarily Natural
      Killer Cell (NK) genes, discriminated between TS and all controls. Granzyme B and
      NKG7 were confirmed using RT-PCR. Five probesets (four genes) reside in
      chromosomal regions previously linked to familial TS or obsessive-compulsive
      disorder. Using the 14 genes, a Principal Components Analysis as well as a
      cluster analysis identified a TS subgroup (n = 10/16) that overexpressed the NK
      genes. 7/10 subjects within this subgroup were diagnosed with attention-deficit
      hyperactivity disorder (ADHD), suggesting that this expression profile might be
      associated with TS and co-morbid ADHD. Principal Components Analysis of gene
      expression in blood may be useful for identifying subgroups of other complex
      neurodevelopmental diseases, and the gene expression profile identified in this
      study may provide a biomarker for at least one subgroup of heritable TS.

PMID- 17503478
TI  - Long-range GABAergic projection neurons in the cat neocortex.
AB  - Neocortical gamma-aminobutyric acid (GABA)ergic neurons have been previously
      described as largely involved in local intracortical circuitry. However, our
      recent findings in the murine model described select neocortical GABAergic
      neurons that project to both neighboring and more distant neocortical regions.
      Here, we investigated whether such GABAergic projection neurons are also found in
      the cat neocortex. Wheat germ agglutinin-conjugated horseradish peroxidase (WGA
      HRP) was injected into the visual, auditory, or somatosensory cortex, in order to
      label efferent cortical neurons retrogradely and to label axons and terminals
      orthogradely. Staining for nicotinamide adenine dinucleotide phosphate diaphorase
      (NADPH-d), an enzyme involved in nitric oxide synthesis, was employed, and co
      localization with WGA-HRP was determined by means of both polarizing and
      brightfield microscopy. We concluded that neurons double-labeled with WGA-HRP and
      NADPH-d in a distant region from the WGA-HRP-injection site are GABAergic neurons
      with long-range projection axons. All double-labeled neurons were found in
      cortical layers VIa and VIb and in the white matter. Neurons with intense NADPH-d
      reactivity (type I) were determined to be neuronal nitric oxide synthase (nNOS)
      positive in all cases. However, weakly NADPH-d-reactive neurons (type II) lacked
      nNOS immunoreactivity. Moreover, nNOS often co-localized with GABA, neuropeptide
      Y, and somatostatin in the cat neocortex. In summary, the GABAergic neurons
      described here projected in a manner similar to that previously described for
      neocortical principal neurons, although some unique GABAergic long-range
      projections were also demonstrated.

PMID- 17503479
TI  - Renal gangliosides are involved in lead intoxication.
AB  - The biological effects of lead are well defined; however, neither the risk
      exposure level nor the subcellular mechanism of its action is completely clear.
      The present work was undertaken to investigate the effects of low level and long
      term lead exposure on the composition and expression of rat renal gangliosides.
      In order to identify ganglioside expression, frozen sections of kidneys were
      stained with monoclonal antibodies GMB16 (GM1 specific), GM28 (GM2 specific), AMR
      10 (GM4 specific) and CDW 60 (9-O-Ac-GD3 specific). Strong reactivity was
      observed for GMB28, AMR-10 and CDW 60, while GMB16 developed only weak labelling
      in treated kidney compared with the control. The alterations in the expression of
      renal gangliosides observed by immunohistochemistry were accompanied by
      quantitative and qualitative changes in the thin layer chromatography of total
      gangliosides isolated from kidney tissues. Lead treatment produced a significant
      increase in 9-O-Ac GD3, a ganglioside involved in apoptotic processes. In
      agreement with this result, a significant decrease in the number of apoptotic
      glomerular cells was observed with the TUNEL assay. These findings lead us to
      suggest that alterations in renal gangliosides produced by low level lead
      exposure are associated with the apoptotic processes that take place in the
      kidney. These findings provide evidence that low level and long term lead
      exposure produces renal ganglioside alterations with urinary microalbumin
      excretion. The results suggest that lead levels within the limits of biological
      tolerance already cause molecular renal damage without clinical signs of
      toxicity.

PMID- 17503480
TI  - Genetic susceptibility to environmental toxicants in ALS.
AB  - Environmental toxicants such as heavy metals, pesticides, and chemicals appear to
      be risk factors for sporadic amyotrophic lateral sclerosis (SALS). An impaired
      ability to break down these toxicants because of differences in detoxification
      genes could underlie some cases of this disease. We therefore examined the
      frequencies of single nucleotide polymorphisms (SNPs) in 186 SALS patients and
      186 controls at the allele, genotype, and haplotype levels for the
      metallothionein (MT) family of genes, metal transcription factor-1 (MTF-1), and
      glutathione synthetase (GSS). Exposure to heavy metals, solvents/chemicals, and
      pesticides/herbicides was assessed by questionnaire, and gene-toxicant
      interactions were analyzed. An intronic SNP upstream of MT-Ie differed in SALS
      patients and controls at the allele and genotype levels. Haplotypes covering MT-I
      isoforms also differed between the two groups. Alleles and genotypes of one MTF-1
      SNP differed in female SALS patients. One GSS haplotype interacted with both
      metals and solvents/chemicals to increase the risk of the disease. Differences in
      genes involved in handling toxicants, and interactions between toxicants and
      these genes, appear to be present in some patients with SALS. This suggests that
      impaired detoxification mechanisms play a role in SALS.

PMID- 17503481
TI  - The opioid system in alcohol and drug dependence: family-based association study.
AB  - Opioid receptors and their endogenous peptide ligands play important roles in
      neurotransmission and neuromodulation in response to addictive drugs such as
      heroin, cocaine, and alcohol. In an earlier study, we reported that variation in
      the genes encoding the kappa-opioid receptor (OPRK1) and its peptide ligand
      (PDYN) were associated with the risk for alcoholism. We continued our
      investigation of the role of the opioid system in alcohol dependence by analyzing
      the genes encoding the micro- and delta-opioid receptors and their peptide
      ligands. We analyzed 18 OPRM1 SNPs, 18 OPRD1 SNPs, 7 PENK SNPs, and 7 POMC SNPs
      in a sample of 1923 European Americans from 219 multiplex alcohol dependent
      families. Employing a family-based test of association, we found no evidence that
      these four genes were significantly associated with alcohol dependence. We also
      did not find association between these genes and illicit drug dependence.
      Secondary analyses employing the narrower phenotype of opioid dependence (83
      affected individuals) demonstrated association with SNPs in PENK and POMC, but
      not in OPRM1 or OPRD1. Haplotype analyses provided further support for the
      association of PENK and POMC with opioid dependence. Therefore, our data provide
      no support for the idea that variations in OPRM1, OPRD1, PENK and POMC are
      associated with alcohol dependence or general illicit drug dependence, but
      variations in PENK and POMC appear to be associated with the narrower phenotype
      of opioid dependence in these families.

PMID- 17503482
TI  - Choline acetyltransferase variants and their influence in schizophrenia and
      olanzapine response.
AB  - Choline acetyltransferase (ChAt) is extensively distributed throughout the CNS
      where, by catalyzing acetylcholine synthesis, it participates in modulating wide
      ranging cholinergic-dependent functions including cognitive performance, sleep,
      arousal, movement, and visual information processing. Recently, compelling
      evidence has mounted implicating ChAt in schizophrenia. In particular, studies
      have identified significant reductions in ChAt activity in the nucleus accumbens
      and pontine tegmentum of such patients, which furthermore correlate significantly
      with measures of cognitive performance in the disorder. Similarly, elevated
      levels of choline, the acetylcholine precursor, have been identified among
      patients, implicating altered ChAt activity in these individuals. We sought to
      investigate the potential contribution of three ChAt gene polymorphisms in
      schizophrenia, and uncovered evidence for significant association between one of
      these, rs1880676G/A, and disease susceptibility among Basque individuals
      (genotypewise chi(2) = 20.7, P = 0.00003; allelewise chi(2) = 10.1, P = 0.002). A
      similar trend for association with susceptibility was observed for a second SNP,
      rs3810950G/A, (genotypwise chi(2) = 6.4, P = 0.05; allelewise chi(2) = 3.75, P =
      0.05). Evidence was also uncovered for a potential influence of these
      polymorphisms on olanzapine treatment outcome among Spanish patients (F-statistic
      = 5.02, P = 0.03; F-statistic = 6.53, P = 0.02 respectively), and on improvements
      in positive symptoms in the case of rs3810950 (F-statistic = 5.3, P = 0.03) and
      general psychopathology in the case of rs1880676 and rs3810950 (F-statistic =
      5.24, P = 0.03; F-statistic = 5.31, P = 0.03 respectively) during therapy. While
      more comprehensive studies are warranted to determine the precise contribution of
      ChAt mediated mechanisms in schizophrenia, our findings tentatively implicate a
      genetic influence of ChAt in the disorder's susceptibility and treatment.

PMID- 17503483
TI  - Multiple topographically organized projections connect the central nucleus of the
      inferior colliculus to the ventral division of the medial geniculate nucleus in
      the gerbil, Meriones unguiculatus.
AB  - The ventral division of the medial geniculate nucleus (MGv) receives almost all
      of its ascending input from the ipsilateral central nucleus of the inferior
      colliculus (CNIC). In a previous study (Cant and Benson [2006] J. Comp. Neurol.
      495:511-528), we made injections of biotinylated dextran amine into the CNIC of
      the gerbil and demonstrated that it can be divided into two parts. One part (zone
      1) receives almost all of its ascending input from the cochlear nuclei, the
      nuclei of the lateral lemniscus, and the main nuclei of the superior olivary
      complex; the other part (zone 2) receives inputs from the cochlear nuclei and
      nuclei of the lateral lemniscus but few or no inputs from the main olivary
      nuclei. Here we show that these two parts of the CNIC project differentially to
      the MGv. Axons labeled anterogradely by injections in zone 1 project throughout
      the rostral two-thirds of the MGv, whereas axons from zone 2 project to the
      caudal third of the MGv. Throughout much of their extent, the terminal fields do
      not appear to overlap, although both parts of the CNIC project to medial and
      dorsal parts of the MGv, and there may be overlap in the most ventral part as
      well. The results indicate that two parallel pathways arising in the CNIC remain
      largely separate in the medial geniculate nucleus of the gerbil. It seems most
      likely that the neurons in the two terminal zones in the MGv perform different
      functions in audition.

PMID- 17503484
TI  - Variations in worker compensation claims by company: the potential for achieving
      a significant reduction in claims.
AB  - BACKGROUND: The objective of our study was to examine the potential reduction in
      paid worker compensation claims if the rate of claims were as low as the rates of
      the top companies in that industry category. METHODS: Using Michigan data for the
      years 1999-2001, we first excluded companies who had no paid worker compensation
      claims for wage replacement and then calculated the top 10th, 25th, and 50th
      percentile rates of paid worker compensation claims for wage replacement of all
      the remaining companies combined and by 2 digit SIC. The percent reduction was
      calculated separately for small (<20 employees) and large companies based on the
      differences in observed minus expected if all companies did as well as the top
      companies in their industry grouping. RESULTS: Fifty-nine percent of large
      companies and 90% of small companies had no paid worker compensation claims for
      wage replacement over the 3-year period. Controlling for industry type there
      would have been 91,504 fewer paid workers' compensation claims if all companies
      with at least one claim did as well as the 10th percentile or better as the
      companies in their industry grouping. Reductions were found across all industries
      and for both small and large companies. CONCLUSION: Variations in worker
      compensation claims between states are highlighted when legislators consider
      "reforms" to reduce workers' compensation costs. These reforms overlook the
      larger variation between companies within the same type of industry in the same
      state. Possible reasons for this variation between companies and its implication
      on reducing morbidity and health care costs are discussed.

PMID- 17503485
TI  - Defects in reciprocal projections between the thalamus and cerebral cortex in the
      early development of Fezl-deficient mice.
AB  - Fez-like (Fezl), the forebrain embryonic zinc finger-like protein, is a
      transcriptional repressor selectively expressed in the deep layers of the
      developing cortex. We examined the thalamocortical and corticofugal pathways in
      Fezl-deficient fetal mice by using immunohistochemistry and by axonal labeling
      with the lipophilic dyes DiI and DiA, with special attention to the
      spatiotemporal relation between thalamocortical and corticofugal axons. In normal
      mice, thalamic and cortical axons meet in the internal capsule between embryonic
      day (E) 13.5 and E14.5 and fasciculate with each other as they extend to their
      targets, the cortex and thalamus, respectively. In Fezl-deficient mice, most of
      the thalamic and cortical axons stop in the internal capsule and at the pallial
      subpallial boundary at E14.5, respectively. This abnormality is transient, and
      the thalamic and cortical axons reach their targets at E15.5, although the number
      of thalamic axons is remarkably reduced in the cortical anlage. Double labeling
      with DiI and DiA demonstrated close apposition of the thalamic and cortical axons
      in the subpallium and pallium as well as in the external capsule of this mutant
      after E15.5. Because the expression of genes that define the pallial-subpallial
      boundary and guidance molecules of thalamocortical axons did not show remarkable
      changes in Fezl-deficient mice, abnormal formation of thalamocortical pathway in
      this mutant may be caused by the defect of axons of cortical efferent neurons
      that express Fezl.

PMID- 17503486
TI  - Systemic administration of the benzodiazepine receptor partial inverse agonist FG
      7142 disrupts corticolimbic network interactions.
AB  - The medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) coordinate
      various stress responses. Although the effects of stressors on mPFC and BLA
      activity have been previously examined, it remains unclear to what extent
      stressors affect functional interactions between these regions. In vivo
      electrophysiology in the anesthetized rat was used to examine mPFC and BLA
      activity simultaneously in response to FG-7142, a benzodiazepine receptor partial
      inverse agonist that mimics various stress responses, in an attempt to model the
      effects of stressors on corticolimbic functional connectivity. Extracellular unit
      and local field potential (LFP) recordings, using multielectrode arrays
      positioned in mPFC and BLA, were conducted under basal conditions and in response
      to systemic FG-7142 administration. This drug increased mPFC and BLA unit firing
      at the lowest dose tested, whereas higher doses of FG-7142 decreased various
      burst firing parameters in both regions. Moreover, LFP power was attenuated at
      lower (<1 Hz) and potentiated at higher frequencies in mPFC (1-12 Hz) and BLA (4
      8 Hz). Interestingly, FG-7142 diminished synchronized unit firing, both within
      and between mPFC and BLA. Finally, FG-7142 decreased LFP synchronization between
      these regions. In a separate group of animals, pretreatment with the selective
      benzodiazepine receptor antagonist flumazenil blocked the changes in burst
      firing, LFP power and synchronized activity induced by FG-7142, confirming direct
      benzodiazepine receptor-mediated effects. These results indicate that FG-7142
      disrupts corticolimbic network interactions via benzodiazepine receptor partial
      inverse agonism. Perturbation of mPFC-BLA functional connectivity induced by FG
      7142 may provide a useful model of corticolimbic dysfunction induced by
      stressors.

PMID- 17503487
TI  - Timing and contributions of pre-synaptic and post-synaptic parameter changes
      during unitary plasticity events at CA3-CA1 synapses.
AB  - At individual synapses, post-synaptic responses include a mixture of "successes"
      and "failures" in which transmitter is released or not released, respectively.
      Previously we measured synaptic strength at CA3-CA1 synapses averaged over all
      trials, including both successes and failures, using an induction protocol that
      allowed us to observe potentiation and depression events as step-like changes.
      Here we report quantal properties of 15 of the earlier experiments, including 14
      potentiation events and eight depression events. In five experiments both
      potentiation events and depression events were evoked at the same synapse. During
      potentiation, success rate increased from 0.56 +/- 0.14 (mean +/- SD) to 0.69 +/-
      0.12, and during depression, success rate decreased from 0.70 +/- 0.09 to 0.51 +/
      0.10. During potentiation potency increased from 10 +/- 5 to 19 +/- 9 pA, and
      during depression, potency decreased from 18 +/- 12 to 12 +/- 7 pA. On average,
      changes in potency accounted for 76% of the change in response size in
      potentiation events and 60% of the change in depression events. A reduced
      assumption spectral analysis method showed evidence for multiple quantal peaks in
      distributions of post-synaptic current amplitudes. Consistent with the observed
      changes in potency, estimated quantal size (Q) increased with potentiation and
      decreased with depression. A change in potency, which is thought to reflect post
      synaptic expression mechanisms, was followed within seconds to minutes by a
      change in success rate, which is thought to reflect pre-synaptic expression
      mechanisms. Synaptic plasticity events may therefore consist of changes that
      occur on both sides of a synapse in a temporally coordinated fashion.

PMID- 17503488
TI  - Changes in vesicular transporters for gamma-aminobutyric acid and glutamate
      reveal vulnerability and reorganization of hippocampal neurons following
      pilocarpine-induced seizures.
AB  - The reorganizations of the overall intrinsic glutamatergic and gamma-aminobutyric
      acid (GABA)-ergic hippocampal networks as well as the time course of these
      reorganizations during development of pilocarpine-induced temporal lobe epilepsy
      were studied with in situ hybridization and immunohistochemistry experiments for
      the vesicular glutamate transporter 1 (VGLUT1) and the vesicular GABA transporter
      (VGAT). These transporters are particularly interesting as specific markers for
      glutamatergic and GABAergic neurons, respectively, whose expression levels could
      reflect the demand for synaptic transmission and their average activity. We
      report that 1) concomitantly with the loss of some subpopulations of VGAT
      containing neurons, there was an up-regulation of VGAT synthesis in all remaining
      GABA neurons as early as 1 week after pilocarpine injection. This enhanced
      synthesis is characterized by marked increases in the relative amount of VGAT
      mRNAs in interneurons associated with increased intensity of axon terminal
      labeling for VGAT in all hippocampal layers. 2) There was a striking loss of
      mossy cells during the latent period, demonstrated by a long-term decrease of
      VGLUT1 mRNA-containing hilar neurons and associated loss of VGLUT1-containing
      terminals in the dentate gyrus inner molecular layer. 3) There were aberrant
      VGLUT1-containing terminals at the chronic stage resulting from axonal sprouting
      of granule and pyramidal cells. This is illustrated by a recovery of VGLUT1
      immunoreactivity in the inner molecular layer and an increased VGLUT1
      immunolabeling in the CA1-CA3 dendritic layers. These data indicate that an
      increased activity of remaining GABAergic interneurons occurs during the latent
      period, in parallel with the loss of vulnerable glutamatergic and GABAergic
      neurons preceding the reorganization of glutamatergic networks.

PMID- 17503489
TI  - Distribution pattern of tachykinin NK2 receptors in human colon: involvement in
      the regulation of intestinal motility.
AB  - Although a number of pharmacological studies have shown the involvement of
      tachykinin type 2 receptors (NK2r) in the regulation of human colonic motility,
      few data are available so far on their pattern of expression. In this study this
      pattern was investigated in the myenteric plexuses, the longitudinal and circular
      muscle layers (external muscular layers), and the interstitial cells of Cajal
      (ICCs) using confocal microscopy immunofluorescence methods. NK2r
      immunoreactivity (NK2r-IR) was detected in the soma of myenteric neurons and in
      nerve varicosities located in myenteric plexuses as well as in external muscular
      layers. Colocalization analysis of NK2r-IR and synaptophysin-IR, showed
      significant regional differences in the distribution of NK2r-expressing nerve
      varicosities, the rate of occurrence was found to be 56.08% +/- 3% (mean +/- SE)
      in the external muscular layers and 30.22% +/- 1% (mean +/- SE) in the myenteric
      plexuses. NK2r-IR was found in membranes of most muscle cells previously
      incubated with a selective NK2r agonist, [beta-Ala(8)] neurokinin A fragment 4
      10, at 4 degrees C, and then mainly relocated in the cytoplasm when heated to 37
      degrees C. A number of NK2r-IR nerve varicosities were close to NK2r-expressing
      neurons and muscle cells. Some of NK2r-expressing neurons and nerves were
      tachykinin-IR. No NK2r-IR was detected in ICCs. The present data indicate that
      presynaptic and postsynaptic neuroneuronal and neuromuscular regulatory processes
      mediated by tachykinins via NK2r may occur for modulating human colonic motility.

PMID- 17503490
TI  - Organization of the human medial preoptic nucleus.
AB  - The organization of the adult human medial preoptic nucleus was studied by using
      chemoarchitectonic markers for acetylcholinesterase, nonphosphorylated
      neurofilament protein (SMI-32), calbindin-D28k, neuropeptide Y (NPY), melanin
      concentrating hormone (MCH), cocaine- and amphetamine-regulated transcript
      (CART), and 3-fucosyl-N-acetyl-lactosamine (CD15) to establish human homologs to
      the subnuclei making up MPO in the rat, where their connections and functional
      significance are better understood. The human MPO comprises three subnuclei, the
      medial MPO, the lateral MPO, and the dorsomedially positioned uncinate
      subnucleus. As in the rat, the human medial MPO is magnocellular and contains
      numerous NPY- and CART-immunoreactive fibers and terminals as well as calbindin
      positive neurons. The human lateral MPO, like its homolog in the rat,
      distinctively features numerous MCH-positive fibers and terminals as well as SMI
      32-immunoreactive fibers. The uncinate subnucleus is wedged between the lateral
      surface of the paraventricular nucleus and the medial MPO and is characterized by
      variable NPY- and CART-immunoreactive fibers and terminals, also seen in the rat
      central MPO, suggesting that the subnuclei are homologues. The intermediate
      nucleus was distinguished by CD15-positive neuronal staining, whereas the
      majority of its neurons also contained acetylcholinesterase. The human
      intermediate nucleus is positioned on the lateral surface of MPO and by its chemo
      and cytoarchitecture constitutes a distinct nucleus of the preoptic area
      characterized by close structural association with the MPO complex. These
      findings demonstrate that the human MPO is organized similarly to the rat MPO, in
      chemo- and cytoarchitectonically distinct subnuclei, which implies differences in
      their functional specialization, as seen in the rat.

PMID- 17503491
TI  - Monocyte activation in response to polyethylene glycol hydrogels grafted with RGD
      and PHSRN separated by interpositional spacers of various lengths.
AB  - Polyethylene glycol (PEG) is often cited as a "stealth" polymer, capable of
      resisting both protein adsorption and cell adhesion. By extension, PEG would then
      be expected to limit the host response. Monocyte-derived macrophages play an
      integral role in inflammation, and thus their response to a material can
      potentially dictate the overall host response to a biomaterial. In the present
      study, monocyte responses following interaction with a photopolymerized PEG
      hydrogel were compared with those from standard tissue culture polystyrene
      (TCPS). Additionally, the effect of the spacing between RGD and PHSRN, the
      corresponding synergy sequence on fibronectin (FN), was evaluated using peptides
      with differing spacer lengths grafted to the PEG hydrogel. Monocyte adherent
      density on the PEG-only hydrogel was comparable with that of TCPS; however, the
      secretion of the proinflammatory molecules interleukin-1beta (IL-1beta), tumor
      necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony stimulating
      factor (GM-CSF) increased dramatically following monocyte interaction with PEG
      only hydrogels as compared with TCPS. The matrix metalloproteinase-2 (MMP-2)
      concentration was similar for all surfaces, while both the matrix
      metalloproteinase-9 (MMP-9) and FN concentrations were above the range of the
      assay for all substrates. Cell density was higher on the PHSRNG(13)RGD grafted
      substrate as compared with PHSRNG(6)RGD, but neither sequence increased cell
      density versus RGD alone. Although protein concentration did sometimes vary with
      different peptides, this variation was minimal in comparison with the surface
      effects between TCPS and the PEG-only hydrogel. This study explores the roles of
      PEG and FN-derived peptides on monocyte activation.

PMID- 17503492
TI  - Evaluation of cellular organization and axonal regeneration through linear PLA
      foam implants in acute and chronic spinal cord injury.
AB  - There are few studies of neural implants in spinal cord injury (SCI) focused on
      supporting directed axon growth. In this study, we fabricated a macroporous poly
      (lactic acid) (PLA) foam with oriented inner channels. Amorphous foam without
      linear channels served as a control in an acute SCI injury model, and the
      effectiveness of foam with linear channels was further investigated in a chronic
      SCI model. Implants were placed into a 2 mm hemisection lesion cavity at the T8
      spinal cord level in adult rats. Two weeks post-implantation, tissue sections
      including the implants were examined using antibodies against GFAP, p75, ED-1,
      laminin, GAP-43, and CGRP. Foam implants were well-integrated with the host
      spinal cord. In linear foams, numerous DAPI-stained cells were found within the
      inner channels. Schwann cells but not astrocytes had migrated within the
      channels. Intense laminin staining was observed throughout the extracellular
      matrix substrate. GAP-43- and CGRP-positive axons grew through the implants
      following the linear channels. In the amorphous control foams, DAPI staining
      distributed evenly through the pores. However, the growth of GAP-43 or CGRP
      positive axons was misguided and impeded at the entrance area of the foam. Higher
      numbers of GAP-43 and CGRP-positive axons grew into linear foam implants after
      chronic SCI than acute SCI. These results suggest the potential application of
      linear foam implants in cell and axon guidance for SCI repair, especially for
      chronic SCI.

PMID- 17503493
TI  - Characterization, degradation, and mechanical strength of poly(D,L-lactide-co
      epsilon-caprolactone)-poly(ethylene glycol)-poly(D,L-lactide-co-epsilon
      caprolactone).
AB  - A series of three biocompatible P(CL-co-LA)-PEG-P(CL-co-LA) copolymers were
      synthesized using ring-opening polymerization and characterized by 1H-NMR, gel
      permeation chromatography, DSC, dynamic-mechanical analysis, and X-ray
      diffraction. The number of monomer units was kept constant, while the D,L-LA
      fraction was varied so as to constitute 0, 30, or 70% of the end segments. The
      molecular weights were sufficiently high to eventually permit 3D scaffold
      preparation. A degradation study was carried out over 26 weeks, and the effect of
      monomer composition on the rate of degradation as well as on changes in
      mechanical strength was investigated. Pure polycaprolactone (PCL)-poly(ethylene
      glycol) (PEG)-PCL copolymer, P(100/0), was a crystalline material displaying no
      measurable mass loss, a 30% reduction in mean molecular weight (Mn), and only
      very slight changes in tensile strength. The random incorporation of 30 and 70%
      D,L-LA into the end sections of the polymer chain, produced more and more
      amorphous materials, exhibiting increasingly high rates of degradation, mass
      loss, and loss of tensile strength. Compared with random P(CL-co-LA), the
      presence of the PEG block was found both to improve hydrophilicity and thus the
      rate of degradation and to infer a stabilizing quality, thereby pacing the
      decrease in tensile strength during degradation. The tested copolymers range from
      materials exhibiting low mechanical strength and high rate of degradation to slow
      degrading materials with high mechanical strength suitable, e.g., for three
      dimensional scaffolding.

PMID- 17503494
TI  - Cytocompatible gel formation of chitosan-glycerol phosphate solutions
      supplemented with hydroxyl ethyl cellulose is due to the presence of glyoxal.
AB  - To deliver and retain viable repair cells in a surgically prepared cartilage
      lesion, we previously developed an adhesive in situ-gelling cell carrier by
      suspending cells in a solution of hydroxyethyl cellulose (HEC), which was then
      mixed with chitosan-glycerol phosphate to form a chitosan-GP/HEC gel. The purpose
      of this study was to elucidate the mechanism of gelation to maximally control gel
      time and viability of encapsulated cells. We analyzed the role of osmolality, pH,
      gelation temperature, gel shrinkage, and HEC. A chitosan-GP solution at pH 6.8
      with cytocompatible osmotic pressure (419 mOsm/kg) was achieved by lowering
      disodium GP concentration from 370 to 135 mM. This solution was still
      thermogelling but only at 73 degrees C. We next discovered that glyoxal, a common
      additive in ether cellulose manufacturing, was responsible for chitosan gelation.
      Monolayer cells survived and proliferated in up to 1 mM of glyoxal, however only
      a very narrow range of glyoxal concentration in chitosan-GP/HEC, 0.1-0.15 mM,
      permitted gel formation, cell survival, and cell proliferation. Chitosan gels
      containing HEC required slightly less glyoxal to solidify. Chitosan-GP/HEC loaded
      with viable chondrocytes formed an adhesive seal with ex vivo mosaic arthroplasty
      defects from sheep knee joints. In mosaic arthroplasty defects of live sheep,
      bleeding occurred beneath part of the hydrogel carrier, and the gel was cleared
      after 1 month in vivo. These data indicate that chitosan-GP/HEC is suitable as an
      adhesive and injectable delivery vehicle for clinical orthopedic applications
      involving single use treatments that guide acute cartilage repair processes.

PMID- 17503495
TI  - Incidence and angiographic predictors of collateral function in patients with
      stable coronary artery disease scheduled for percutaneous coronary intervention.
AB  - OBJECTIVES: To investigate the incidence and angiographic predictors of
      functional collateral perfusion in patients with stable coronary artery disease,
      scheduled for elective PCI. BACKGROUND: Functional collateral perfusion is
      defined as a Pw/Pa ratio>or=0.24. Since this can only be measured intracoronary,
      it is important to investigate baseline clinical and angiographic predictors for
      functional collateral perfusion. METHODS: Collateral perfusion was measured
      during balloon inflation, with the use of a pressure-monitoring guide wire.
      Baseline clinical and angiographic characteristics were analyzed and collateral
      grading was done according to Rentrop's classification for coronary angiograms.
      RESULTS: Functional collateral perfusion was found in 40 of the 89 patients
      (45%). Angiographic signs of collaterals (Rentrop>or=1) were present in 15 of the
      89 patients. Of the 40 patients with the functional collateral perfusion 11
      patients (28%) had Rentrop>or=1; of the 49 patients without functional
      collaterals there were 4 patients with Rentrop>or=1 (8%) (P=0.02). There were no
      significant differences in baseline clinical characteristics or in other
      angiographic characteristics. CONCLUSIONS: In patients with stable coronary
      artery disease scheduled for elective PCI, 45% have functional collaterals.
      Rentrop's angiographic classification can be used to predict the presence or
      absence of functional collaterals, however with a rather modest positive and
      negative predictive value.

PMID- 17503496
TI  - Sheath stabilizing technique for balloon sizing of large atrial septal defects
      response to article by Dr. Zahid Amin entitled "Transcatheter closure of secundum
      atrial septal defects".

PMID- 17503497
TI  - Effects of aging on contact heat-evoked potentials: the physiological assessment
      of thermal perception.
AB  - Age significantly influences the detection thresholds to noxious heat; such
      thresholds depend on responses in the cerebral cortex to thermal stimuli and the
      psychophysical perception of such responses. To understand the influence of age
      on cerebral responses, we used contact heat-evoked potentials (CHEPs) to
      investigate the physiology of cerebral responses to thermal stimuli in 70 healthy
      subjects (33 men and 37 women, 39.56 +/- 12.12 years of age). With heat
      stimulation of fixed intensity (51 degrees C) on the distal forearm and distal
      leg, CHEPs revealed consistent waveforms with an initial negative peak (N1
      latency: 398.63 +/- 28.55 and 449.03 +/- 32.21 ms for upper and lower limbs) and
      a later positive peak (P1 latency: 541.63 +/- 37.92 and 595.41 +/- 39.24 ms for
      upper and lower limbs) with N1-P1 interpeak amplitude of 42.30 +/- 12.57 microV
      in the upper limb and 39.67 +/- 12.03 microV in the lower limb. On analyses with
      models of multiple linear regression, N1-P1 amplitudes were negatively correlated
      with age and N1 latencies were correlated with gender, with females having
      shorter latencies. The verbal rating scale (VRS) for pain perception was higher
      in females than males, and decreased with aging. In addition, VRS paralleled
      changes in N1-P1 amplitude and N1 latency; the higher the VRS, the shorter the N1
      latency and the higher the N1-P1 amplitude. These results provide evidence that
      CHEPs are influenced significantly by aging, corresponding to aging-related
      changes in thermal pain perception.

PMID- 17503499
TI  - Pathogenic mitochondrial DNA mutations in protein-coding genes.
AB  - More than 200 disease-related mitochondrial DNA (mtDNA) point mutations have been
      reported in the Mitomap (http://www.mitomap.org) database. These mutations can be
      divided into two groups: mutations affecting mitochondrial protein synthesis,
      including mutations in tRNA and rRNA genes; and mutations in protein-encoding
      genes (mRNAs). This review focuses on mutations in mitochondrial genes that
      encode proteins. These mutations are involved in a broad spectrum of human
      diseases, including a variety of multisystem disorders as well as more tissue
      specific diseases such as isolated myopathy and Leber hereditary optic neuropathy
      (LHON). Because the mitochondrial genome contains a large number of apparently
      neutral polymorphisms that have little pathogenic significance, along with
      secondary homoplasmic mutations that do not have primary disease-causing effect,
      the pathogenic role of all newly discovered mutations must be rigorously
      established. A scoring system has been applied to evaluate the pathogenicity of
      the mutations in mtDNA protein-encoding genes and to review the predominant
      clinical features and the molecular characteristics of mutations in each mtDNA
      encoded respiratory chain complex.

PMID- 17503498
TI  - Mathematical model that predicts the force-intensity and force-frequency
      relationships after spinal cord injuries.
AB  - We have previously developed and tested a muscle model that predicts the effect
      of stimulation frequency on muscle force responses. The aim of this study was to
      enhance our isometric mathematical model to predict muscle forces in response to
      stimulation trains with a wide range of frequencies and intensities for the
      quadriceps femoris muscles of individuals with spinal cord injuries. Isometric
      forces were obtained experimentally from 10 individuals with spinal cord injuries
      (time after injury, 1.5-8 years) and then compared to forces predicted by the
      model. Our model predicted accurately the force-time integrals (FTI) and peak
      forces (PF) for stimulation trains of a wide range of frequencies (12.5-80 HZ)
      and intensities (150-600-mus pulse duration), and two different stimulation
      patterns (constant-frequency trains and doublet-frequency trains). The accurate
      predictions of our model indicate that our model, which now incorporates the
      effects of stimulation frequency, intensity, and pattern on muscle forces, can be
      used to design optimal customized stimulation strategies for spinal cord-injured
      patients.

PMID- 17503500
TI  - Iron load and redox stress in skeletal muscle of aged rats.
AB  - Loss of skeletal muscle mass (sarcopenia) is a major contributor to disability in
      old age. We used two-dimensional gel electrophoresis and mass spectrometry to
      screen for changes in proteins, and cDNA profiling to assess transcriptional
      regulations in the gastrocnemius muscle of adult (4 months) and aged (30 months)
      male Sprague-Dawley rats. Thirty-five proteins were differentially expressed in
      aged muscle. Proteins and mRNA transcripts involved in redox homeostasis and iron
      load were increased, representing novel components that were previously not
      associated with sarcopenia. Tissue iron levels were elevated in senescence,
      paralleling an increase in transferrin. Proteins involved in redox homeostasis
      showed a complex pattern of changes with increased SOD1 and decreased SOD2. These
      results suggest that an elevated iron load is a significant component of
      sarcopenia with the potential to be exploited clinically, and that mitochondria
      of aged striated muscle may be more vulnerable to radicals produced in cell
      respiration.

PMID- 17503501
TI  - Rat alpha- and gamma-motoneuron soma size and succinate dehydrogenase activity
      are independent of neuromuscular activity level.
AB  - The chronic level of neuromuscular activity, that is, activation and loading,
      strongly influences the morphological, metabolic, phenotypic, and physiological
      properties of skeletal muscles. The effects on the innervating motoneurons,
      however, are less established. We determined and compared the effects of 30 days
      of decreased activity (induced by a complete mid-thoracic spinal cord
      transection, ST) or near inactivity (induced by spinal cord isolation, SI) on the
      soma size and succinate dehydrogenase (SDH) activity of motoneurons innervating a
      predominantly slow ankle extensor (soleus) and a predominantly fast ankle flexor
      (tibialis anterior) muscle of adult rats. Soleus and tibialis anterior motoneuron
      pools were labeled retrogradely using nuclear yellow. The alpha- and gamma
      motoneurons were classified based on soma size. Mean number of labeled
      motoneurons, and mean soma size and SDH activity for both alpha- and gamma
      motoneurons were similar in control, ST, and SI rats. Compared to previous
      reports showing significant decreases in muscle fiber size and adaptations toward
      a "faster" metabolic profile following ST and SI, the results indicate that,
      unlike the muscles they innervate, the motoneurons are relatively unresponsive to
      chronic reductions in neuromuscular activity. The implication of these results is
      that mean size and SDH activity are independent of the number of action
      potentials generated by both alpha- and gamma-motoneurons and that even the
      absence of afferent input to the spinal cord has no influence on size and
      oxidative metabolic potential of the motoneuron soma.

PMID- 17503502
TI  - Simple and novel method to measure distal sensory nerve conduction of the medial
      plantar nerve.
AB  - A simple and reliable method for recording sensory nerve action potentials
      (SNAPs) of the medial plantar nerve is described. Medial plantar SNAPs were
      recorded by placing surface electrodes on the sole. Ring electrodes were used for
      orthodromic stimulation at the big toe. Sixty-four healthy subjects ranging in
      age from 13 to 81 years were examined to establish normal values. Mean amplitude
      for the medial plantar SNAP was 4.7 +/- 2.8 microV and mean maximum conduction
      velocity was 43.5 +/- 6.4 m/s. The normal values for amplitude obtained for the
      medial plantar SNAPs were higher than those obtained by the method of Guiloff and
      Sherratt, and the sensitivity of our method for diagnosis of early sensory
      neuropathy was relatively higher. The method should therefore be useful in the
      diagnosis of early sensory neuropathy.

PMID- 17503503
TI  - Comparison between sirolimus- and paclitaxel-eluting stents in complex patient
      and lesions subsets.
AB  - BACKGROUND: Sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES)
      both significantly reduce the need for repeat intervention compared to bare metal
      stents. Studies comparing the clinical outcomes of these stents in noncomplex
      subsets of patients and lesions demonstrate a similar safety and efficacy
      profile. The data for more complex subsets of patients and lesions remains
      conflicting. This study aimed to compare SES with PES in a selected population
      with a broad range of complex features. METHODS AND RESULTS: The patient
      population consisted of 1,591 consecutive patients with complex features
      undergoing drug-eluting stent (DES) implantation. In the SES group there were
      1,095 patients (1,653 lesions) and in the PES group 496 patients (802 lesions).
      In-hospital, 30-day, and 12-month clinical outcomes were compared between groups.
      No discernable difference in major adverse cardiac events (MACE) between SES and
      PES was detected at intermediate and longer-term follow-up (SES 22.4% vs. PES
      20.5% at 12 months; P=0.407). A trend toward increased angiographically
      documented stent thrombosis was observed in the SES group at both 3 and 12 months
      (SES 2.2% vs. PES 0.8% at 12 months; P=0.051). When adopting the more inclusive
      definition of probable stent thrombosis, this trend was no longer seen. After
      adjusting for baseline differences between the two groups, there still remained
      no difference in MACE between SES and PES (HR 1.051 [CI 0.826-1.339] P=0.685).
      The trend toward increased angiographically documented stent thrombosis in the
      SES group remained after adjustment for baseline differences (HR 2.836 [CI 0.968
      8.311] P=0.057). CONCLUSIONS: In a selected population with complex disease the
      rate of MACE was comparable between SES and PES, with higher overall rates of
      thrombosis and MACE compared to a noncomplex population. Thus, the focus should
      be directed to prevent late complications in this complex subset regardless of
      stent type selection.

PMID- 17503504
TI  - Effects of a CRF2R agonist and exercise on mdx and wildtype skeletal muscle.
AB  - Corticotrophin-releasing factor 2 receptor (CRF2R) agonists prevent muscle
      atrophy due to immobilization, denervation, and corticosteroid-induced muscle
      atrophy in wildtype mice. We hypothesized that a CRF2R agonist will increase
      skeletal muscle mass in mdx mice. Mdx (C57BL/10ScSn-Dmd(mdx)) and wildtype
      (C57BL/6) mice were divided into four groups: sedentary placebo, sedentary CRF2R
      agonist, exercised placebo, and exercised CRF2R agonist. Mice exercised on a
      treadmill twice weekly for 30 min (8-12 m/min, 8 weeks). Muscle and heart
      weights, serum creatine kinase, and gamma-glutamyltransferase activities were
      measured. The CRF2R agonist increased extensor digitorum longus and soleus muscle
      weights (P < 0.05) in wildtype and mdx mice. Sedentary mdx CRF2R and exercised
      mdx placebo mice had lower serum creatine kinase activity than sedentary mdx
      placebo mice. CRF2R-treated mice had decreased heart weights compared to placebo
      treated mice. We conclude that CRF2R agonists should be further evaluated as a
      potential therapy for dystrophinopathies.

PMID- 17503505
TI  - Fas small interfering RNA reduces motoneuron death in amyotrophic lateral
      sclerosis mice.
AB  - OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal
      neurodegenerative disease characterized by selective motoneuron death.
      Understanding of the molecular mechanisms that trigger and regulate motoneuron
      degeneration could be relevant to ALS and other motoneuron disorders. This study
      investigates the role of Fas-linked motoneuron death in the pathogenesis of ALS.
      METHODS: We performed in vitro and in vivo small interfering RNA-mediated
      interference, by silencing the Fas receptor on motoneurons that carry the
      superoxide dismutase-1 (SOD1)-G93A mutation. RESULTS: We observed a significant
      reduction in Fas expression at messenger RNA (p < 0.001) and protein levels.
      Treated motoneurons demonstrated an increase in survival and a reduction in
      cytochrome c release from mitochondria. In vivo, continuous intrathecal
      administration of Fas small interfering RNA by an osmotic minipump improved motor
      function and survival in SOD1-G93A mice (mean increase, 18 days; p < 0.0001).
      Treated mice showed a significant reduction in Fas and Fas mediators p38 mitogen
      activated protein kinase, neuronal nitric oxide synthase, and caspase-8.
      INTERPRETATION: Fas silencing interferes with motoneuron-specific downstream
      death pathways and results in increased motoneuron survival and amelioration of
      the SOD1-G93A phenotype, suggesting new possible strategies for molecular therapy
      of ALS.

PMID- 17503506
TI  - Increased levels of circulating endothelial progenitor cells and circulating
      endothelial nitric oxide synthase in patients with gliomas.
AB  - OBJECTIVE: Gliomas are among the highest vascularized tumors. We hypothesized
      that patients with gliomas have increased levels of circulating endothelial
      progenitor cells (EPCs) and circulating endothelial nitric oxide synthase (eNOS).
      METHODS: The fraction of EPCs was quantified by fluorescence-activated cell
      sorter analysis using anti-CD34, -CD133 and -KDR (kinase insert domain receptor)
      monoclonal antibodies in unselected peripheral blood samples of 32 patients with
      gliomas. Control groups included 47 patients with other central nervous system
      tumors or diseases, 10 patients with recent ischemic strokes, and 19 healthy
      blood donors. The circulating eNOS concentration of plasma was measured by a
      colorimetric assay in the same samples. In addition, CD34(+)CD105(+) KDR(+) and
      CD34(+)CD146(+)KDR(-) cell fractions were measured. RESULTS: The percentage of
      CD34(+)CD133(+)KDR(+) EPCs in the blood of glioma patients is significantly
      greater than that in the blood of patients with other central nervous system
      tumors or diseases (p = 0.003), stroke patients (p = 0.005), or healthy donors (p
      = 0.013). The plasma eNOS concentration is also significantly greater in glioma
      patients compared with each of the control groups (p < 0.001 for all groupwise
      comparisons). No significant differences in the levels of the EPCs or eNOS
      between any of the control groups were demonstrated. In the glioma patients, the
      level of eNOS correlated with the fraction of CD34(+)CD105(+)KDR(+) cells (r =
      0.748; p = 0.008). INTERPRETATION: The data are suggestive of increased
      mobilization of EPCs contributing to neoplastic vasculogenesis in glioma. The
      increased levels of EPCs and eNOS in the peripheral blood of glioma patients
      trigger further investigations as to their value as independent parameters for
      use in clinical practice.

PMID- 17503507
TI  - DBH -1021C-->T does not modify risk or age at onset in Parkinson's disease.
AB  - DBH is a candidate gene in Parkinson's disease (PD) and contains a putative
      functional polymorphism (-1021C-->T) that has been reported to modify PD
      susceptibility. We examined -1021C-->T in a sample of 1,244 PD patients and 1,186
      unrelated control subjects. There was no significant difference in allele (p =
      0.14) or genotype (p = 0.26) frequencies between the two groups. A similar result
      was obtained after pooling our data with those previously published. Furthermore,
      we found no evidence for an effect of genotype on age at onset among patients.
      Our findings argue against DBH -1021C-->T as a risk factor or age at onset
      modifier in PD.

PMID- 17503508
TI  - Hybrid approach to surgical correction of tetralogy of Fallot in all patients
      with functioning Blalock Taussig shunts.
AB  - BACKGROUND: In total surgical correction of tetralogy of Fallot (TOF) with
      functioning Blalock Taussig shunts (BTS), shunt take down increased surgical
      time, bleeding, and might injure phrenic and recurrent laryngeal nerve and
      thoracic duct. OBJECTIVES: A routine hybrid approach using transcatheter BTS
      closure immediately before total surgical correction of TOF in all patients might
      reduce these problems. We analyze the safety and feasibility of this approach.
      METHODS: Transcatheter BTS closure was achieved using single or multiple
      stainless steel embolization coils, Amplatzer vascular plugs, or duct occluders.
      When coils were released without control by bioptome forceps, coil migration in
      larger shunts was prevented by proximal or distal balloon occlusion. RESULTS:
      This routine hybrid strategy was followed in 22 consecutive patients aged 1-13
      years over 4-year-period and 21 procedures were successful. Among the 16 patients
      attempted with coils, 13 had successful closure, 2 needed Amplatzer duct occluder
      devices, and 1 sent for surgical shunt takedown due to acute angulation of the
      shunt. New Amplatzer vascular plugs were used in six patients. Bioptome was used
      in six patients and proximal or distal balloon occlusion of flow was used in
      three patients. Four patients had closure of associated aortopulmonary or chest
      wall collaterals. CONCLUSION: Hybrid approach using routine transcatheter closure
      of all BTS immediately before surgical correction of TOF shunts with
      coils/plugs/devices is safe, feasible, and reproducible.

PMID- 17503509
TI  - Comparison of in vivo acute stent recoil between the bioabsorbable everolimus
      eluting coronary stent and the everolimus-eluting cobalt chromium coronary stent:
      insights from the ABSORB and SPIRIT trials.
AB  - OBJECTIVES: This study sought to evaluate and compare in vivo acute stent recoil
      of a novel bioabsorbable stent and a metallic stent. BACKGROUND: The
      bioabsorbable everolimus-eluting coronary stent (BVS) is composed of a poly-L
      lactic acid backbone, coated with a bioabsorbable polymer containing the
      antiproliferative drug, everolimus, and expected to be totally metabolized and
      absorbed in the human body. Because the BVS is made from polymer, it may have
      more acute recoil than metallic stents in vivo. METHODS: A total of 54 patients,
      who underwent elective stent implantation for single de novo native coronary
      artery lesions, were enrolled: 27 patients treated with the BVS and 27 patients
      treated with the everolimus-eluting cobalt chromium stent (EES). Acute absolute
      recoil, assessed by quantitative coronary angiography, was defined as the
      difference between mean diameter of the last inflated balloon at the highest
      pressure (X) and mean lumen diameter of the stent immediately after the last
      balloon deflation (Y). Acute percent recoil was defined as (X - Y)/X and
      expressed as a percentage. RESULTS: Acute absolute recoil of the BVS and EES was
      0.20 +/- 0.21 mm and 0.13 +/- 0.21 mm, respectively (P = 0.32). Acute percent
      recoil was 6.9% +/- 7.0% in the BVS group and 4.3% +/- 7.1% in the EES group (P =
      0.25). CONCLUSIONS: In vivo acute stent recoil of the BVS is slightly larger but
      insignificantly different from that of the EES, implying that the BVS may have
      good radial strength similar to the metallic stent.

PMID- 17503510
TI  - The Anchor-Tornus technique: a novel approach to "uncrossable" chronic total
      occlusions.
AB  - Following successful guidewire passage, inability to cross a chronic total
      occlusion is the most frequent cause of procedural failure. While low-profile
      balloons, microcatheters, and specialty catheters such as the Tornus have been
      designed to facilitate lesion crossing, these devices require adequate guiding
      catheter support. We describe a novel application of the Tornus catheter combined
      with a balloon-anchored guide technique to successfully recanalize an otherwise
      difficult to cross chronic total occlusion.

PMID- 17503511
TI  - Late vascular response at the edges of sirolimus analogous-eluting stents in
      diabetic patients: An intravascular ultrasound study.
AB  - INTRODUCTION: Vascular response at edges of drug-eluting stents is still not well
      established, particularly in diabetic patients who are prone to aggressive
      atherosclerosis progression. Recently, Biolimus and Zotarolimus have demonstrated
      potent antiproliferative effects. OBJECTIVE: To compare the vascular responses at
      edges of sirolimus analogous-eluting stents in patients with and without
      diabetes, using intravascular ultrasound (IVUS). METHODS: 306 edges were analyzed
      in 153 patients treated with drug-eluting stents and divided in: diabetics (122
      edges) and nondiabetics (166 edges). IVUS was performed postintervention and at 6
      month follow-up and included 5 mm distal and proximal to the stented segment.
      Vessel, lumen, and plaque volumes were calculated. Volume variation (follow-up
      minus basal) was also calculated. Edge restenosis was defined as obstruction
      >50%. RESULTS: Baseline characteristics were similar between groups. In both
      groups the entire lesion length was covered (stent length/lesion length ratio was
      1.5 for both groups). There were no differences in edge volumes and restenosis
      rate between the groups. Among diabetics, there was no significant volume
      variation. However, in nondiabetic patients there was significant increase in
      vessel volume in proximal (from 67.1 +/- 22 mm(3) to 72.2 +/- 25 mm(3): P = 0.02)
      and distal (from 54.4 +/- 22 mm(3) to 59.8 +/- 22 mm(3): P = 0.001) edges.
      CONCLUSION: Nondiabetic patients showed a significant positive vascular
      remodeling in proximal and distal edges of sirolimus analogous-eluting stent.
      This vascular mechanism was not observed in diabetic patients. Although different
      vascular responses were observed, restenosis rates were equivalent between the 2
      groups at 6-month follow-up.

PMID- 17503512
TI  - Astrocytes are a specific immunological target in Rasmussen's encephalitis.
AB  - OBJECTIVE: The current histopathological criteria of Rasmussen's encephalitis
      (RE) include the presence of T-cell-dominated inflammation, microglial
      activation, neuronal loss, and astrocytic activation. An in vitro study, however,
      suggested glutamate receptor 3 (GluR3) antibody-mediated astrocytic loss.
      Therefore, we investigated astrocytic apoptosis and loss in situ. METHODS:
      Histochemical, immunohistochemical, terminal deoxynucleotidyltransferase-mediated
      biotin-dUTP nick end labeling and in situ hybridization techniques were applied
      to paraffin sections of 20 RE cases, 6 healthy control subjects, and 6
      paraneoplastic encephalomyelitis, 10 Ammon's horn sclerosis, and 5 focal cortical
      dysplasia cases. RESULTS: Astrocytic apoptosis and subsequent loss of these cells
      is a specific feature of RE. Such lesions are not found in the control groups. In
      RE, astrocytic apoptosis and loss was present both in cortical and in white
      matter areas. Astrocytes in these tissues showed major histocompatibility complex
      class I expression. Furthermore, granzyme-B(+) lymphocytes were found in close
      apposition to astrocytes bordering astrocyte-deficient lesions. Granzyme-B(+)
      granules in these lymphocytes were polarized and faced the astrocytic membranes.
      No evidence was found for an antibody-mediated destruction. INTERPRETATION: We
      suggest a specific attack by cytotoxic T lymphocytes as a possible mechanism
      responsible for astrocytic degeneration in RE. The loss of astrocytes might play
      a role in neuronal dysfunction, seizure induction, and enhancement of neuronal
      cell death.

PMID- 17503513
TI  - Clinical and genetic study of autosomal recessive cerebellar ataxia type 1.
AB  - OBJECTIVE: Define the phenotype and genotype of a cluster of families with a
      relatively pure cerebellar ataxia referred to as autosomal recessive cerebellar
      ataxia type 1 (ARCA-1). METHODS: We ascertained 64 probands and affected members
      of 30 French-Canadian families all showing similar clinical features and
      originating from the same region of Quebec. After informed consent, we performed
      detailed clinical history, neurological examination, brain imaging, nerve
      conduction studies, and SYNE1 mutation detection of all available subjects.
      RESULTS: Based on the cases examined, ARCA-1 is a cerebellar syndrome
      characterized by recessive transmission, middle-age onset (mean, 31.60; range, 17
      46 years), slow progression and moderate disability, significant dysarthria, mild
      oculomotor abnormalities, occasional brisk reflexes in the lower extremities,
      normal nerve conduction studies, and diffuse cerebellar atrophy on imaging. We
      identified a total of seven mutations in our population, thereby providing
      evidence of genotypic heterogeneity. Patients with different mutations did not
      show significant phenotypic heterogeneity. INTERPRETATION: We identified a
      cluster of French-Canadian families with a new recessive ataxia of relatively
      pure cerebellar type caused by mutations in SYNE1. The function of SYNE1 is thus
      critical in the maintenance of cerebellar structure in humans. We expect that
      this disease will be a common cause of middle-age-onset recessive ataxia
      worldwide.

PMID- 17503514
TI  - Subcortical infarcts, Alzheimer's disease pathology, and memory function in older
      persons.
AB  - OBJECTIVE: Examine the effects of subcortical infarcts with Alzheimer's disease
      (AD) pathology on dementia, episodic memory, and other cognitive abilities in
      older persons. METHODS: Participants included 148 autopsied subjects of the Rush
      Memory and Aging Project (mean age, 88.0 years), a longitudinal
      clinicopathological study. Cognition was assessed yearly with 21
      neuropsychological tests. Infarcts were visualized on coronal slabs, and plaques
      and neurofibrillary tangles were counted and standardized to form a composite
      measure of AD pathology. Multiple regression analyses were used controlling for
      age, sex, and education. RESULTS: Fifty-three (35.8%) subjects had cerebral
      infarcts. After accounting for AD pathology, infarcts increased the odds of
      dementia by 5.1-fold (95% confidence interval, 1.98-12.92) and lowered cognitive
      function by 0.50 standard unit (p = 0.001). After controlling for cortical
      infarcts and AD pathology, subcortical infarcts, present in 39 of 53 (73.6%)
      subjects with infarcts, increased the odds of dementia by almost 4-fold and
      reduced cognitive function by more than a third of a unit (parameter estimate = 
      0.37; p = 0.03). In analyses with cognitive abilities, subcortical infarcts were
      associated with lower episodic, semantic, and working memory (p < or = 0.05), and
      had an interaction with AD pathology to further worsen working memory (p = 0.02).
      INTERPRETATION: Subcortical infarcts add to deleterious effects of AD pathology
      by increasing the odds of dementia and lowering memory function.

PMID- 17503515
TI  - Feasibility of transcatheter intervention for severe aortic stenosis in patients
      >or=90 years of age: aortic valvuloplasty revisited.
AB  - OBJECTIVES: The goals of this study were to determine the feasibility, safety,
      and early outcomes of balloon aortic valvuloplasty (BAV) for severe aortic
      stenosis in a nonagenarian population. BACKGROUND: This very elderly population
      is expanding rapidly, has a high incidence of aortic stenosis, and uncommonly
      undergoes surgical aortic valve replacement. These patients may best be treated
      with a transcatheter approach due to comorbidities, surgical risk, and personal
      preference. METHODS: We reviewed 31 consecutive patients >or=90 years of age who
      underwent BAV at our institution from July 2003 to August 2006 for data pertinent
      to patient characteristics, procedural techniques, and 30-day outcomes. RESULTS:
      Our patients had a mean age of 93 +/- 3.0 years (90-101). The society of thoracic
      surgery risk score was 18.5 (+/-10.2) and logistic Euroscore was 35.8 (+/-19.3).
      Twenty-five patients (81%) underwent retrograde BAV and 6 (19%) antegrade BAV.
      Five patients (16%) underwent combined BAV and coronary stenting. Overall mean
      aortic valve area increased from 0.52 cm2 (+/-0.17) to 0.92 cm2 (+/-0.22) and
      mean New York Heart Association (NYHA) functional class improved from 3.4 to 1.8.
      Intraprocedural mortality occurred in one patient (3.2%) and 30-day mortality in
      three patients (9.7%). CONCLUSIONS: BAV can be carried out in high risk
      nonagenarian patients with an acceptable complication rate, low perioperative
      mortality, and early improvement in NYHA functional class.

PMID- 17503516
TI  - Transcatheter closure of large pulmonary arteriovenous fistula including
      pulmonary artery to left atrial fistula with Amplatzer septal occluder.
AB  - OBJECTIVES: We sought to evaluate the safety and efficacy of Amplatzer septal
      occluder (ASO) to close very large pulmonary arteriovenous fistula (PAVF).
      BACKGROUND: Transcatheter coil embolization, the standard treatment for PAVF, has
      potential complications particularly in patients with very large fistulas.
      Several recently available devices have been tried effectively, however, they too
      have limitations. METHODS: During 2004, three patients (aged 17-56 years),
      diagnosed with large PAVF including one with pulmonary artery (PA) to left atrial
      (LA) fistula, had interventional closure prospectively using ASO. Following
      hemodynamic evaluation and angiographic localization of PAVF, the feeding artery
      (FA) was selectively cannulated with Amplatzer delivery sheath. ASO, with the
      right atrial (RA) disc diameter equal to or up to 4 mm larger than the maximum
      diameter of FA, was delivered through it in such a way that the left atrial disc
      assumed an oblong shape and the right atrial disc retained its designed flat
      configuration for better anchorage and thrombogenicity. RESULTS: All patients had
      very large PAVF fed by a single FA (size 12-24 mm), which was closed completely,
      without complications, using ASO (size 7-16 mm; RA disc diameter 15-26 mm). Their
      arterial saturation rose from mean 72.3% to 97.3%. Follow up (1.5-3 years) showed
      disappearance of the radiological shadows and stable arterial saturations (mean
      97.7%). CONCLUSIONS: We conclude that, using the new criteria for device size
      selection and modified technique of implantation, very large PAVFs including PA
      to LA fistula can be closed safely, effectively and nonsurgically with ASO.

PMID- 17503517
TI  - Normal coronary arteries are rare in young patients with acute myocardial
      infarction.
AB  - OBJECTIVE: To delineate the angiographic extent of coronary atherosclerosis in
      young patients (<45 years) with acute myocardial infarction (MI). BACKGROUND:
      Prior studies suggest 20% of young patients with acute MI have normal coronary
      arteries. However, most such studies defined "normal" as absence of stenoses >50%
      luminal diameter, ignoring the presence of nonflow limiting disease that may
      harbor culprit plaques. METHODS: We retrospectively analyzed 131 patients <45
      years old with ST-segment elevation MI undergoing emergency catheterization.
      Angiograms were analyzed for the presence and extent of disease, including lesion
      "complexity" indicative of plaque instability. "Normal" vessels were defined as
      absence of any disease. RESULTS: Mean patient age was 40 +/- 7 years. The infarct
      related artery and an obvious complex culprit lesion was identified in all (100%)
      cases (left anterior descending 44%, right coronary 38%, and circumflex 18%).
      Single vessel disease involving the culprit vessel only was identified in 60% of
      cases, whereas additional disease was found in 40% of others (two-vessel in 29%
      and three-vessel disease in 11% of patients). CONCLUSION: These findings
      demonstrate that young patients with acute MI typically manifest an identifiable
      complex culprit atherosclerotic coronary lesion. Furthermore, they often have
      multivessel atherosclerosis.

PMID- 17503518
TI  - Neurophysiological effects of mobile phone electromagnetic fields on humans: a
      comprehensive review.
AB  - In recent years a growing number of people have begun to use mobile phone
      technology. This phenomenon has raised questions and doubts about possible
      effects on users' brains. This literature review focuses on the human
      electrophysiological and neuro-metabolic effects of mobile phone (MP)-related
      electromagnetic fields (EMFs) published in the last 10 years. To this end, all
      relevant papers have been reported and, subsequently, a literature selection has
      been carried out by taking several criteria into account, such as: blind
      techniques, randomization or counter-balancing of conditions and subjects, detail
      of exposure characteristics and the statistical analyses used. As a result, only
      the studies meeting the selection criteria have been described, evaluated and
      discussed further. The main goal of this review is to provide a clear scenario of
      the most reliable experiments carried out over the last decade and to offer a
      critical point of view in their evaluation. It is concluded that MP-EMFs may
      influence normal physiology through changes in cortical excitability and that in
      future research particular care should be dedicated to both methodological and
      statistical control, the most relevant criteria in this research field.

PMID- 17503519
TI  - Site-specific CGRP innervation coincides with bone formation during fracture
      healing and modeling: A study in rat angulated tibia.
AB  - Sensory neuropeptide involved in local bone turnover is known, but poorly
      understood. In the present study, we analyze the occurrence of neuronal CGRP
      during healing and modeling of straight and angular tibial fractures in 74 rats.
      Bone healing and modeling was assessed by radiography and reinnervation by semi
      quantitative immunohistochemistry method at fracture site between 1-12 weeks
      postfracture. The regenerating nerve fibers containing CGRP were observed in
      fracture callus as well as in close proximity to chondrocytes, with woven bone in
      both fractures already at week 1. Notably, it located predominantly on the
      concave side of angulated fracture in the manner of sprouting into bone from
      weeks 3 to 5 postfracture. In both fractures, fracture calluses peaked
      radiographically at week 3 postfracture. In angulated fracture, a reduction of
      11% in callus thickness on convex side and an increase of 365% on concave side
      were noted from weeks 3 to 12. A 27-fold increase in total neuronal CGRP in
      straight fracture and 38-fold increases in angular fracture compared to intact
      bone was observed at week 3. In both types of fracture, neuronal CGRP was greater
      on the concave side than the convex; this difference was more pronounced in the
      angulated fracture. CGRP immunoreactivity clearly coincides with amount of new
      bone formation especially on the concave side of angulated fracture. The combined
      results suggest that fracture evokes an intense, localized in-growth of new nerve
      fibers containing CGRP, which may prove to be a prerequisite of fracture healing
      and modeling.

PMID- 17503520
TI  - Effects of BMP-2 and pulsed electromagnetic field (PEMF) on rat primary
      osteoblastic cell proliferation and gene expression.
AB  - Bone morphogenetic proteins (BMPs) strongly promote osteoblast differentiation.
      Pulsed electromagnetic fields (PEMFs) promote fracture healing in non-union
      fractures. In this study, we hypothesized that a combined BMP-2 and PEMF
      stimulation would augment bone formation to a greater degree than treatment with
      either single stimulus. BMP-2 maximally increased the proliferative activity of
      rat primary osteoblastic cells at 25 ng/ml concentration. Real-time reverse
      transcription-polymerase chain reaction (RT-PCR) showed that BMP-2 stimulated
      mRNA levels of alkaline phosphatase (ALP), alpha(1) (I) procollagen, and
      osteocalcin (OC) in the differentiation phase and only OC mRNA expression in the
      mineralization phase after 24-h treatment. Both BMP-2 and PEMF (Spinal-Stim)
      increased cell proliferation, which was additive when both agents were combined.
      PEMF alone or together with BMP-2 increased only ALP mRNA expression and only
      during the differentiation phase 24 h after one 4-h treatment. This effect was
      additive when both agents were combined. Continuous daily 4-h treatment with PEMF
      alone or together with BMP-2 increased expression of all three osteoblast marker
      genes during the differentiation phase and increased the mineralized matrix. This
      effect was additive when both agents were combined, suggesting that the two
      interventions may be working on different cellular pathways. Thus, a combined
      effect of BMP-2 and PEMF in vitro could be considered as groundwork for in vivo
      bone development that may support skeletal therapy.

PMID- 17503521
TI  - Anatomy and biomechanics of the posterolateral aspect of the canine knee.
AB  - The purpose of this study was to describe the anatomy and characterize the
      biomechanics of the posterolateral aspect of the canine knee. Ten adult canine
      knees were each used for anatomy and biomechanical testing. Distances and motion
      limits were measured using a 6 degree-of-freedom electromagnetic tracking system.
      Canine knee dissection reproducibly identified structures present in the human
      posterolateral knee. The course and attachment sites of the fibular collateral
      ligament, popliteofibular ligament, and popliteus tendon were similar to human
      anatomy. Sequential sectioning of the fibular collateral ligament,
      popliteofibular ligament, and popliteus tendon all significantly increased varus
      translation at full extension, 60 degrees , and 90 degrees of knee flexion.
      Sectioning of the fibular collateral ligament significantly increased external
      rotation at flexion angles near full extension, while popliteus tendon sectioning
      also significantly increased external rotation at 90 degrees of knee flexion.
      Based on the fact that the anatomy of the fibular collateral ligament, popliteus
      tendon, popliteofibular ligament, and the biomechanical properties of the canine
      posterolateral knee are similar to the human knee, we believe the canine knee is
      a suitable model to study the natural history of posterolateral knee injuries.
      The canine model will also prove valuable in the validation of reconstruction
      techniques and studying the potential development of medial compartment
      osteoarthritis following posterolateral knee injuries.

PMID- 17503522
TI  - Abstracts of the 47th Teratology Society Annual Meeting and the 20th
      International Conference of the Organization of Teratology Information
      Specialists. June 23-28, 2007. Pittsburgh, Pennsylvania, USA.

PMID- 17503524
TI  - RGDS peptides immobilized on titanium alloy stimulate bone cell attachment,
      differentiation and confer resistance to apoptosis.
AB  - A major cause of implant failure in skeletal tissues is failure of
      osseointegration, often due to lack of adhesion of cells to the titanium (Ti)
      alloy interface. Since arginine-glycine-aspartic acid (RGD)-containing peptides
      have been shown to regulate osteoblast adhesion, we tested the hypothesis that,
      bound to a Ti surface, these peptides would promote osteoblasts differentiation,
      while at the same time inhibit apoptosis. RGDS and RGES (control) peptides were
      covalently linked to Ti discs using an APTS linker. While the grafting of both
      RGDS and RGES significantly increased Ti surface roughness, contact angle
      analysis showed that APTS significantly increased the surface hydrophobicity;
      when the peptides were tethered to Ti, this was reduced. To evaluate attachment,
      MC3T3-E1 osteoblast cells were grown on these discs. Significantly more cells
      attached to the Ti-grafted RGDS then the Ti-grafted RGES control. Furthermore,
      expression of the osteoblasts phenotype was significantly enhanced on the Ti
      grafted RGDS surface. When cells attached to the Ti-grafted RGDS were challenged
      with staurosporine, an apoptogen, there was significant inhibition of apoptosis;
      in contrast, osteoblasts adherent to the Ti-grafted RGES were killed. It is
      concluded that RGD-containing peptides covalently bonded to Ti promotes
      osteoblasts attachment and survival with minimal changes to the surface of the
      alloy. Therefore, such modifications to Ti would have the potential to promote
      osseointegration in vivo.

PMID- 17503525
TI  - Bone response to three different chemical compositions of fluorcanasite glass
      ceramic.
AB  - The aim of this study was to evaluate the bone response to three fluorcanasite
      glass-ceramic compositions with different solubilities (K3, K5, and K8) after
      implantation in a femur rabbit model. Fluorcanasite glass-ceramic rods were
      implanted bilaterally in the mid-shafts rabbit femurs. Implants were harvested at
      8 and 12 weeks and prepared for histological and histomorphometric analyses at
      the light microscope level. Bioglass 45S5 rods were used as a control material.
      At 8 weeks, all fluorcanasite glass-ceramics were entirely surrounded by a
      nonmineralized connective tissue. At 12 weeks, reduced areas of bone tissue were
      observed in the cortical area in direct contact with the K3 and K5 fluorcanasite
      glass-ceramics compared to Bioglass 45S5, whereas no bone tissue was observed in
      direct contact with the K8 surface. Bone-to-implant contact in the cortical area
      was affected by the material chemical composition and ranked as follows: Bioglass
      45S5>K3>K5>K8 (p=0.001). In the bone marrow, a layer of fibrous connective tissue
      formed in direct contact with the fluorcanasite glass-ceramics and Bioglass 45S5,
      and only rarely exhibited contact osteogenesis. All the fluorcanasite glass
      ceramics appeared to degrade in the biological environment. The solubility ratio
      did not alter significantly the biological reply of the fluorcanasite glass
      ceramics in vivo. Further modifications of the chemical composition of the
      fluorcanasite glass-ceramic are required to increase the stability of the
      material in vivo.

PMID- 17503526
TI  - Proteomic analysis and quantification of cytokines and chemokines from
      biomaterial surface-adherent macrophages and foreign body giant cells.
AB  - Implantation of biomaterial devices results in the well-known foreign body
      reaction consisting of monocytes, macrophages, and foreign body giant cells
      (FBGCs) at the material/tissue interface. We continue to address the hypothesis
      that material surface chemistry modulates the phenotypic expression of these
      cells. Utilizing our human monocyte culture system, we have used surface-modified
      polymers displaying hydrophobic, hydrophilic, and/or ionic chemistries to
      determine the cytokines/chemokines released from biomaterial-adherent
      macrophages/FBGCs. This study broadens our approach by using proteomic analysis
      to identify important factors expressed by these cells and further quantifies
      these molecules with ELISAs. Proteomic profiles changed over time suggesting that
      the adherent macrophages underwent a phenotypic switch. Macrophage/FBGC-derived
      proinflammatory cytokines, IL-1beta and IL-6, decreased with time, while the anti
      inflammatory cytokine, IL-10, gradually increased with time. Resolution of the
      inflammatory response was also demonstrated by a decrease in chemoattractant IL-8
      and MIP-1beta production with time. Material-dependent macrophage/FBGC activation
      was analyzed using cytokine/chemokine production and cellular adhesion.
      Monocyte/macrophage adhesion was similar on all surfaces, except for the
      hydrophilic/neutral surfaces that showed a significant decrease in cellular
      density and minimal FBGC formation. Normalizing the ELISA data based on the
      adherent cell population provided cytokine/chemokine concentrations produced per
      cell. This analysis showed that although there were fewer cells on the
      hydrophilic/neutral surface, these adherent cells were further activated to
      produce significantly greater amounts of each cytokine/chemokine tested than the
      other surfaces. This study clearly presents evidence that material surface
      chemistry can differentially affect monocyte/macrophage/FBGC adhesion and
      cytokine/chemokine profiles derived from activated macrophages/FBGCs adherent to
      biomaterial surfaces.

PMID- 17503531
TI  - Chondrogenic differentiation of human mesenchymal stem cells in collagen type I
      hydrogels.
AB  - The chondrogenic differentiation of bone marrow-derived human mesenchymal stem
      cells (MSCs) in a collagen type I hydrogel, which is in clinical use for matrix
      based autologous chondrocyte transplantation (ACT), was investigated. Collagen
      hydrogels with 2.5 x 10(5) MSCs/mL were fabricated and cultured for 3 weeks in a
      serum-free, defined, chondrogenic differentiation medium containing 10 ng/mL TGF
      beta1 or 100 ng/mL BMP-2. Histochemistry revealed morphologically distinct,
      chondrocyte-like cells, surrounded by a sulfated proteoglycan-rich extracellular
      matrix in the TGF-beta1 and BMP-2 treated group, with more elongated cells seen
      in the BMP-2 treated group. Immunohistochemistry detected collagen type II (Col
      II) in the TGF-beta1 and BMP-2 treated group. Collagen type X (Col X) staining
      was positive in the TGF-beta1 but only very weak in the BMP-2 treated group. RT
      PCR analyses revealed a specific chondrogenic differentiation with the expression
      of the cartilage specific marker genes Col II, Col X, and aggrecan (AGN) in the
      TGF-beta1 and the BMP-2 treated group, with earlier expression of these marker
      genes in the TGF-beta1 treated group. Interestingly, MSC-gels cultured in DMEM
      with 10% FBS (control) indicated few isolated chondrocyte-like cells but no
      expression of Col II or Col X could be detected. The results show, that MSCs
      cultured in a collagen type I hydrogel are able to undergo a distinct
      chondrogenic differentiation pathway, similar to that described for MSCs cultured
      in high-density pellet cultures. These findings are valuable in terms of ex vivo
      predifferentiation or in situ differentiation of MSCs in collagen hydrogels for
      articular cartilage repair.

PMID- 17503532
TI  - In vitro water wettability of silicone hydrogel contact lenses determined using
      the sessile drop and captive bubble techniques.
AB  - This study investigated the water contact angles of five commercially available
      silicone hydrogel contact lenses (Acuvue Advance, Acuvue Oasys, Focus Night &
      Day, O2 Optix, and PureVision) using sessile drop and captive bubble techniques.
      The only lens type that showed a significant difference in water contact angle
      when measured by sessile drop direct from the blister compared with after 48 h of
      soaking/washing in saline was the Acuvue Advance lens (from 66 degrees to 96
      degrees, respectively) (p=0.0002), presumably because of surface active agents
      within the blister solution. The water contact angle data split the lenses into
      two distinct groups (p<or=0.002). The Acuvue Advance, Acuvue Oasys, and
      PureVision lenses demonstrated relatively high sessile drop measures and
      relatively low captive bubble values (thereby displaying significant hysteresis)
      whereas the Focus Night & Day and O2 Optix lenses showed relatively low sessile
      drop measures and relatively high captive bubble values (with little hysteresis).
      Contact angle analysis of hydrogel lens surfaces is highly methodologically
      dependent and may be able to predict the clinical performance of contact lenses
      in vivo.

PMID- 17503533
TI  - Photo-crosslinkable and biodegradable Pluronic/heparin hydrogels for local and
      sustained delivery of angiogenic growth factor.
AB  - Photo-crosslinkable and biodegradable Pluronic/heparin composite hydrogels were
      fabricated for local and sustained delivery of basic fibroblast growth factor
      (bFGF) to induce angiogenesis. Terminally di-acrylated Pluronic F127 and vinyl
      group conjugated heparin were used as a mixed macromer precursor solution to
      prepare a photo-crosslinkable hydrogel. An aqueous solution containing the two
      macromers with different weight ratios was photo-crosslinked in the presence of
      bFGF to produce in situ formed bFGF loaded Pluronic/heparin hydrogels. Swelling,
      mass erosion, bFGF release characteristics of Pluronic/heparin hydrogels were
      thoroughly examined by varying the weight ratio of the two macromers. The
      incorporation of heparin in the composite hydrogel enabled the controlled release
      of bFGF over a one month period in a near zero order manner. The prolonged
      release of bFGF could be attributed to the specific interaction between bFGF and
      heparin in the hydrogel matrices. The released bFGF fraction from the degradable
      hydrogels also showed sufficient proliferation activity of human umbilical vein
      endothelial cell (HUVEC). When the Pluronic/heparin hydrogels were implanted in
      vivo, a significant extent of neo-vascularization was observed.

PMID- 17503534
TI  - Assessment of natural and synthetic wollastonite as source for bioceramics
      preparation.
AB  - Pseudowollastonite ceramics (beta-CaSiO3) from synthetic and natural sources were
      assessed with regard to their properties relevant to biomedical applications.
      Synthetic and natural CaSiO3 powders, with average particle size of 1.6 and 13.2
      microm, respectively, were first employed. Powders were pressed and sintered at
      1400 degrees C for 2 h. Pseudowollastonite was the only crystalline phase in
      sintered materials. Glassy phase, eight times more abundant in sintered natural
      wollastonite (SNW) than in the synthetic one (SSW), was observed in grain
      boundaries and in triple points. Larger grains and bigger and more abundant pores
      were present in SNW, resulting in lower diametral tensile strength (26 MPa), than
      in SSW (42 MPa). However, by milling the natural wollastonite starting powder to
      a particle size of 2.0 microm and sintering (SNW-M), the microstructure became
      finer and less porous, and diametral tensile strength increased (48 MPa). Weibull
      modulus of SNW and SNW-M samples was twice that of the SSW. All the samples
      released Si and Ca ions, and removed phosphate ions from simulated body fluid in
      similar amounts and were completely coated by apatite-like spherules after
      soaking in simulated body fluid for 3 wk. The aqueous extracts from all samples
      studied were not cytotoxic in a culture of human fibroblastic cells. No
      differences in fibroblast-like human cells adhesion and proliferation were
      observed between samples. According to the obtained results, properly processed
      pseudowollastonite bioceramics, obtained from the natural source, exhibit the
      same in vitro behavior and better performance in terms of strength and
      reliability than do the more expensive synthetic materials.

PMID- 17503536
TI  - Proteins combination on PHBV microsphere scaffold to regulate Hep3B cells
      activity and functionality: a model of liver tissue engineering system.
AB  - The synergistic effects of extracellular matrix (ECM) protein combinations on
      Hep3B cell proliferation and functions are studied herein. Poly(3-hydroxybutyrate
      co-3-hydroxyvalerate) (PHBV) microspheres were covalently conjugated with three
      types of proteins, collagen (type I), laminin, and fibronectin, using 1-ethyl-3
      (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide cross linkers.
      Successful conjugations of protein molecules were verified by the presence of
      nitrogen peaks in X-ray photoelectron spectroscopy. The densities of grafted
      proteins were quantified using Micro-BCA kit. A human hepatoma cell line, Hep3B,
      was then cultured in vitro on the ECM proteins-modified microspheres for 2 weeks.
      Cell proliferation was estimated using MTT method, and two hepatic functions,
      albumin secretion and P-450 activity, were evaluated using ELISA and EROD assays,
      respectively. The results indicated that combination of the three ECM proteins on
      microsphere surfaces has a significant effect on the proliferation of Hep3B
      cells, thus better mimicking the in vivo environment for liver tissue
      engineering.

PMID- 17503537
TI  - Stability and degradation kinetics of etoposide-loaded parenteral lipid emulsion.
AB  - Etoposide was incorporated in lipid emulsion to develop an i.v. formulation, and
      improve its physical and chemical stability without addition of organic solvents,
      for use as a commercial formulation. High-pressure homogenization was used to
      prepare the lipid nanospheres and localize the drug at the surfactant layer. The
      particle size distribution and zeta potential were measured using photon
      correlation spectroscopy (PCS). Ultrafiltration was used to estimate the relative
      percentage of etoposide in each phase. The stability profile of etoposide in the
      lipid emulsion at various temperatures, pH values, and concentrations of drug was
      monitored by high performance liquid chromatography (HPLC). The degradation
      pattern of etoposide in lipid emulsion followed pseudo-first-order kinetics. The
      shelf life (T(90%)) of etoposide in lipid emulsion was estimated to be 47 days at
      25 degrees C and it would be stable when stored for 427 days at 4 degrees C,
      which is a significant improvement compared with a stability of 9.5 days in
      aqueous solution at 25 degrees C. Etoposide in lipid emulsion and aqueous
      solution were both most stable at pH 5.0 with a half-life of 54.7 h and 38.6 min
      at 80 degrees C, respectively. The hydrolysis kinetics of etoposide in lipid
      emulsion was also shown to be dependent on the drug concentration.

PMID- 17503538
TI  - Optimizing human post-mortem brain tissue gene expression profiling in
      Parkinson's disease and other neurodegenerative disorders: from target "fishing"
      to translational breakthroughs.
AB  - Insights on the etiopathogenesis of common neurodegenerative disorders such as
      Parkinson's disease (PD) and Alzheimer's disease (AD) have been largely based on
      the discovery of gene mutations in genetically determined forms. Although these
      discoveries have been helpful in elucidating the basic molecular pathogenesis of
      familial forms, they represent a small fraction of cases, leaving the large
      majority classified as idiopathic. In the postgenomic era, brain tissue gene
      expression profiling has allowed relative quantitative assessment of thousands of
      genes simultaneously from one tissue sample, providing clues for novel candidate
      genes and processes implicated in neurodegenerative disorders. Some remain
      critical of "fishing expedition" science, but gene expression profiling is a
      discovery-based procedure well suited for the study of largely idiopathic and
      multifactorial diseases. However, the technology is still under development, and
      many methodological and biological aspects contribute to the heterogeneous
      results obtained from gene expression profiling. In this Review, we discuss the
      advantages and limitations of this technology in simple terms and identify the
      key variables that influence/limit gene expression profiling-derived
      translational breakthroughs in neurodegenerative diseases.

PMID- 17503541
TI  - Acute stress disorder in older, middle-aged and younger adults in reaction to the
      second Lebanon war.
AB  - OBJECTIVES: To compare rate of acute stress disorder (ASD) and intensity of acute
      stress symptoms (ASS) in younger, middle-aged and older Israeli citizens exposed
      to missile attacks during the second Lebanon war. METHOD: A telephone survey of a
      random sample of residents in the northern area of Israel was conducted in July
      2006, during the third week of Lebanon war. Respondents were divided into groups
      aged 18-40, 41-69 and 70+. ASD and ASS were measured by the Acute Stress
      Interview questionnaire and by war-related exposure variables and demographic
      data. RESULTS: Exposure variables were similar in the three age groups. Older
      respondents reported lower intensity of ASS and obtained lower means for each of
      the symptoms criteria than the young adults, while the middle-aged adults were in
      between the younger and the older group. ASD criteria were met by 13.2% of the
      younger, 4.7% of middle-aged and 4.3% of older respondents (p > 0.05), and
      subsyndromal ASD was found in 20.5%, 14.1% and 4.4% (p < 0.05) respectively.
      Twenty-two percent of ASS variance was explained by younger age, female gender
      and higher perceived proximity to missile falling. CONCLUSIONS: Older adults
      reacted to the war situation with lower level of acute stress symptoms. Long-term
      effects of war on different age groups should be further studied.

PMID- 17503543
TI  - The treatment of mild Alzheimer's disease post-NICE.

PMID- 17503542
TI  - Religiosity of depressed elderly inpatients.
AB  - OBJECTIVES: To determine the prevalence of religious practices and beliefs of
      depressed elderly Australian inpatients and their relationship to physical,
      social, and cognitive variables known to influence the prognosis of depression in
      the elderly. To compare the results obtained with those from similar North
      American studies. METHODS AND PROCEDURES: Inpatients with a DSM-IV diagnosis of
      major depression were interviewed on admission to the psychogeriatric unit of a
      Melbourne geriatric centre. Information collected included patient demographics,
      intrinsic and extrinsic religiosity, cognitive function, severity of depression,
      number of chronic illnesses, physical function, and numbers and quality of social
      support. Pearson correlation and multivariate analysis using a standard
      regression model were used to examine relationships between the religious and
      other variables. RESULTS: Of the 86 patients who completed the assessment, 25%
      attended church regularly and 37% prayed, meditated, or read the Bible, at least
      once a day. Just over half rarely or never engaged in such behaviours. Three out
      of every eight patients were 'intrinsically' religious. Religious patients
      expressed higher levels of social support and physically disabled patients were
      more likely to be religious. CONCLUSIONS: Depressed elderly Australian inpatients
      are less religious than their North American counterparts. Nevertheless, religion
      remains important for a large minority of such individuals. Clinicians need to be
      aware that such individuals may turn to religion when depressed, especially to
      cope with the presence of physical disability.

PMID- 17503544
TI  - Quality of life in dementia: a 2-year follow-up study.
AB  - OBJECTIVES: To examine the evolution of quality of life (QOL) in demented
      subjects at base-line, one and 2 years later and to determine clinical variables
      associated with QOL. METHOD: Longitudinal study of a cohort of 127 subjects
      living at home or in a long-term care institution. A QOL measure (Alzheimer
      Disease Related Quality of Life; ADRQL) was administered three times. In
      addition, several clinical instruments (MMSE, IADL, ADL and CDR/M) were also
      administered. RESULTS: ADRQL data analysis did not reveal significant
      modifications of QOL over the 2-year period, whereas results from clinical
      instruments showed a significant deterioration. On the group, the variations of
      ADRQL scores were limited, with some improvement after the first year followed by
      some deterioration after the second year. On the other hand, ADRQL scores
      fluctuated every year by at least 10 points for more than 50% of subjects. With
      dementia evolution, it was observed that the clinical variables were more
      strongly correlated with ADRQL scores and were more significant predictors. This
      varied from 5.9% (MMSE) in 2002 to 40.01% in 2004 (MMSE and CDR/M). CONCLUSIONS:
      QOL did not develop in a strictly linear manner following the deterioration of
      clinical state. This suggests that the evolution of QOL is also determined by
      other variables relating to the physical and social environment of the patients.
      Their role seems particularly important for the mild to moderate stages of
      dementia.

PMID- 17503545
TI  - Group reminiscence therapy for cognitive and affective function of demented
      elderly in Taiwan.
AB  - BACKGROUND: Elderly people with cognitive impairments are often associated with
      depressed mood and are heavy consumers in both medical services and need in
      caregivers. Reminiscence is believed to be effective in improving the cognition
      and mood of demented people. OBJECTIVES: This study tested the hypothesis that
      structured group reminiscence therapy can prevent the progression of cognitive
      impairment and enhance affective function in the cognitively impaired elderly.
      METHODS: A randomized controlled trial (RCT) based on a two group pre- and post
      test design was used. The experimental subjects underwent eight group sessions,
      one session per week. The measurements were performed using Mini-Mental State
      Examination (MMSE), Geriatric Depression Scale short form (GDS-SF), and Cornell
      Scale for Depression in Dementia (CSDD). RESULTS: The sample consisted of 102
      subjects, with 51 in the experimental group and 51 in the control group. Results
      demonstrated that the intervention significantly affected cognitive function and
      affective function as measured by MMSE and CSDD (p = 0.015 and 0.026), indicating
      that the cognitive function of the experimental subjects increased and their
      depressive symptoms diminished following intervention. CONCLUSION: Participation
      in reminiscence activities can be a positive and valuable experience for demented
      older persons. Consequently, the development of a structured care program for
      elderly persons with cognitive impairment and the need for long-term care is
      essential. Thus, health providers in long-term care facilities should be trained
      in reminiscence group therapy, and to be able to deliver such a program to the
      targeted group.

PMID- 17503546
TI  - Morphometric analysis for early detection of changes in cellular structure in a
      toxicological experiment.
AB  - This paper presents a method for semi-automatic analysis of morphometry in image
      cytometry studies. We examine morphological changes in neuroblastoma cells caused
      by a toxin. Nuclei are automatically recognized from images using a constrained
      seeded region growing algorithm. The shape of the nuclei is quantified by fitting
      ellipses to the identified regions. Features such as centroids, elongation,
      orientation and size are extracted from this fitting process. Under certain
      assumptions, it is demonstrated that the log elongation measurement has an
      asymptotically normal distribution whose variance is dependent only on object
      size. This allows weighted linear models to be fitted to elongation measurements.
      Hypothesis tests show that over time, there is a significant elongation due to
      application of the toxin. The other variables are not significant, but there is a
      significant 'image' effect. The scientific implications of these findings are
      considered.

PMID- 17503549
TI  - What is "junk" DNA, and what is it worth?

PMID- 17503547
TI  - HIV integrase inhibitors as therapeutic agents in AIDS.
AB  - HIV-1 integrase is a protein of Mr 32 000 encoded at the 3'-end of the pol gene.
      Integration of HIV DNA into the host cell chromosomal DNA apparently occurs by a
      carefully defined sequence of DNA tailoring (3'-processing (3'P)) and coupling
      (integration) reactions. Integration of HIV DNA into human DNA represents the
      biochemical completion of the invasion of the human cell (e.g., T-cell) by HIV.
      Unlike major successes seen in the development of clinically approved anti-HIV
      agents against HIV reverse transcriptase and HIV protease, there are no FDA
      approved anti-HIV drugs in clinical use where the mechanism of action is
      inhibition of HIV integrase. This review summarises some key advances in the area
      of integrase inhibitors with the major focus being on new generation inhibitors.
      Special emphasis is placed on diketo acids with aromatic and heteroaromatic
      moieties, diketo acids with nucleobase scaffolds, bis-diketo acids,
      functionalised naphthyridines and other isosteres of diketo acids. Data
      pertaining to integrase inhibition and in vitro anti-HIV activity are discussed.
      Mention is made of drugs in clinical trials, both past (S-1360, L-870,810 and L
      870,812 and present (GS-9137 and MK-0518). Other promising drugs, including those
      from the authors' laboratory, are referred. Resistant mutants arising from key
      integrase inhibitors and cross-resistance are indicated.

PMID- 17503550
TI  - Pulmonary veno-occlusive disease.

PMID- 17503551
TI  - Behavior and substance addictions: is the world ready for a new category in the
      DSM-V?

PMID- 17503552
TI  - [Reminder: Meeting of the Radiotherapy and Oncology Specialty College on
      September 22nd, 2006].

PMID- 17503553
TI  - [Report from the First Hungarian Congress of Eating Disorders, Budapest,
      September 22-23, 2006].

PMID- 17503554
TI  - Gold Medalist Tribute. Hedvig Hricak, MD, PhD.

PMID- 17503555
TI  - Intractable spastic cerebral palsy in children: a Dutch cost of illness study.

PMID- 17503556
TI  - Re: severe memory impairment in a child with bihippocampal injury after status
      epilepticus.

PMID- 17503557
TI  - [Experimental substantiation of the ICP MS study of elementary content of teeth
      to diagnose medicobiological characteristics of humans].

PMID- 17503558
TI  - [About ways of attached gum forming in the region of dental implants].

PMID- 17503559
TI  - [Comparative toxicological evaluation of domestic golden alloys for soldering].

PMID- 17503560
TI  - [Further introduction of specialists in family dentistry in the system of health
      care].

PMID- 17503561
TI  - [Preoperative factors influencing the early results of infrainguinal limb salvage
      procedures].
AB  - INTRODUCTION: The early results of 59 patients treated surgically for critical
      limb ischemia at the Institute of Cardiovascular Diseases were analyzed. Research
      was performed in a prospective manner, as an acute study, lasting for three
      months. OBJECTIVE: Our focus was on primary and secondary patency rate, and graft
      efficacy (quality accomplished by graft patency, improvement of clinical status
      of the leg, and quality of life). METHOD: The influence of each variable on the
      outcome was analyzed (descriptive: sex, comorbidity, risk factors, clinical stage
      of disease, angiographic verification of pedal arch, previous vascular
      procedures; and numerical: gender, preoperative Doppler index, angiographic score
      by Bollinger), as well as their predictive value. Inferential statistics was used
      for establishing the significance of influence, and univariate regression
      analysis for predictive values. RESULTS: No influence of variables on the outcome
      was evident in the first three months, and their predictive value was not
      important considering the graft patency rates and efficacy (except for
      preoperative clinical status affecting the graft efficacy, presence of pedal
      arch, affecting both primary and secondary patency rates and graft efficacy, and
      finally Doppler index affecting the secondary patency rates). CONCLUSION: When
      the surgeon needs to give an early prediction of graft destiny, he can rely on
      preoperative clinical status, earlier vascular operative procedures, presence of
      pedal arch, and values of Doppler index (in case of reintervention).

PMID- 17503562
TI  - [Prognostic value of Poincare plot as nonlinear parameter of chaos theory in
      patients with myocardial infarction].
AB  - INTRODUCTION: There are different proofs about association of autonomic nervous
      system dysfunction, especially nonlinear parameters, with higher mortality after
      myocardial infarction. OBJECTIVE: The objective of the study was to determine
      predictive value of Poincare plot as nonlinear parameter and other significant
      standard risk predictors: ejection fraction of the left ventricle, late
      potentials, ventricular arrhythmias, and QT interval. METHOD: The study included
      1081 patients with mean follow-up of 28 months (ranging from 0-80 months). End
      point of the study was cardiovascular mortality. The following diagnostic methods
      were used during the second week: ECG with commercial software Schiller AT-10:
      short time spectral analysis of RR variability with analysis of Poincare plot as
      nonlinear parameter and late potentials; 24-hour ambulatory ECG monitoring: QT
      interval, RR interval, QT/RR slope, ventricular arrhythmias (Lown > II);
      echocardiography examinations: systolic disorder (defined as EF < 40%). RESULTS:
      There were 103 (9.52%) cardiovascular deaths during the follow-up. In univariate
      analysis, the following parameters were significantly correlated with mortality:
      mean RR interval < 800 ms, QT and RR interval space relationship as mean RR
      interval < 800 ms and QT interval > 350 ms, positive late potentials, systolic
      dysfunction, Poincare plot as a point, ventricular arrhythmias (Lown > II). In
      multivariate analysis, the significant risk predictors were: Poincare plot as a
      point and mean RR interval lower than 800 ms. CONCLUSION: Mean RR interval lower
      than 800 ms and nonlinear and space presentation of RR interval as a point
      Poincare plot were multivariate risk predictors.

PMID- 17503563
TI  - [Brain natriuretic peptide as a predictor of heart failure in patients with
      permanent pacemaker].
AB  - INTRODUCTION: Brain natriuretic peptide (BNP) has a role in control of
      cardiovascular and renal functions. OBJECTIVE: The objective was to assess the
      predictive value of BNP levels for development of heart failure in patients with
      permanent pacemakers. METHOD: In patients with implanted DDD pacemakers, BNP
      levels were measured at rest and after exercise testing, on DDD and VVI modes.
      There were 42 patients (25 males; 59.5%), without symptoms or signs of coronary
      disease or heart failure, and with normal echocardiograms. According to BNP
      levels, the patients were divided into three groups: with BNP levels lower than
      80 pg/ml, BNP ranging from 81-150 pg/ml, and BNP levels over 151 pg/ml. RESULTS:
      In the first group (27 patients), BNP levels were significantly higher on VVI
      compared to DDD mode, both at rest and after exercise (p < 0.01), with all BNP
      levels within normal range. In the second group (5 pts), BNP levels at rest were
      also significantly higher on VVI than on DDD mode, p < 0.05. After exercise,
      these values were also higher on VVI compared to DDD mode, but without
      statistical significance. The third group (10 pts) as a whole had higher BNP
      values on VVI compared to DDD mode, with no statistical significance. In patients
      from this group who later developed heart failure, BNP levels were found to be
      significantly lower on DDD as opposed to VVI mode at rest, p < 0.05, and even
      higher significance was found after exercise, p < 0.01. After 6-year follow-up, 2
      out of 5 patients from the second group developed dilated cardiomyopathy, and
      8/10 patients in the third group experienced heart failure with LV EF 34.1 +/-
      10%, LV EDD 6.1 +/- 0.42 cm, LV ESD 4.8 +/- 0.45 cm. Five of these patients died
      within the follow-up period. CONCLUSION: The increased BNP levels can be valuable
      for early screening of patients with higher risk of heart failure. In patients
      with increased BNP at the time of pacemaker implantation, DDD pacing is a
      modality of choice.

PMID- 17503564
TI  - [Comparison of three diagnostic methods to confirm Helicobacter pylori
      infection].
AB  - INTRODUCTION: Helicobacterpylori induces gastric inflammation in host and such
      gastritis increases the risk of gastric and duodenal ulceration as well as
      adenocarcinoma. Because peptic ulcer disease is the major cause of morbidity,
      accurate diagnosis of H. pylori infection is very important. Unfortunately, there
      is no gold standard among diagnostic tests for Helicobacter infections. If
      gastroscopy is performed, histopathology and urease test are the most often used.
      Still, culturing of this bacterium is essential for drug susceptibility testing
      and analysis of virulence factors. OBJECTIVE: The aim of this study was to
      compare three diagnostic procedures--histopathology, urease test and culture,
      which are used to verify H. pylori infection. METHOD: Three pairs of gastric
      mucosal biopsy specimens were collected from each of 28 dyspeptic patients
      undergoing endoscopy. Nineteen patients were not pretreated with antibiotics,
      while nine had received eradication therapy earlier. One pair of biopsy specimens
      was used for histopathologic examination, the second for urease test and the
      third was simultaneously cultured on nonselective and selective solid media.
      Isolate was identified as H. pylori on the basis of colony morphology,
      morphological properties and biochemical tests. RESULTS: In 14 out of 28
      patients, H. pylori infection was confirmed on the basis of results of all
      diagnostic procedures. The concordance of these three methods was very good,
      because the results of histopathology, urease test and culture corresponded in 26
      from 28 patients. CONCLUSION: The conclusion of our study is that culture, as the
      method with high degree of concordance with other two procedures and the only
      that can give information on drug susceptibility of Helicobacter, is recommended
      for diagnosis of Helicobacter pylori infection along with histopathology and
      urease test.

PMID- 17503565
TI  - [The value of corticotropin-releasing hormone (CRH) test for differential
      diagnosis of Cushing's syndrome].
AB  - INTRODUCTION: Diagnosis and differential diagnosis of Cushing's syndrome (CS)
      remain considerable challenge in endocrinology. For more than 20 years, CRH has
      been widely used as differential diagnostic test. Following the CRH
      administration, the majority of patients with ACTH secreting pituitary adenoma
      show a significant rise of plasma cortisol and ACTH, whereas those with ectopic
      ACTH secretion characteristically do not. OBJECTIVE: The aim of our study was to
      assess the value of CRF test for differential diagnosis of CS using the ROC
      (receiver operating characteristic) curve method. METHOD: A total of 30 patients
      with CS verified by pathological examination and postoperative testing were
      evaluated. CRH test was performed within diagnostic procedures. ACTH secreting
      pituitary adenoma was found in 18, ectopic ACTH secretion in 3 and cortisol
      secreting adrenal adenoma in 9 of all patients with CS. Cortisol and ACTH were
      determined -15.0, 15, 30, 45, 60, 90 and 120 min. after i.v. administration of
      100 microg of ovine CRH. Cortisol and ACTH were determined by commercial RIA.
      Statistical data processing was done by ROC curve analysis. Due to small number,
      the patients with ectopic ACTH secretion were excluded from test evaluation by
      ROC curve method. RESULTS: In evaluated subgroups, basal cortisol was (1147.3 +/-
      464.3 vs. 1589.8 +/- 296.3 vs. 839.2 +/- 405.6 nmol/L); maximal stimulated
      cortisol (1680.3 +/- 735.5 vs. 1749.0 +/- 386.6 vs. 906.1 +/- 335.0 nmol/L); and
      maximal increase as a percent of basal cortisol (49.1 +/- 36.9 vs. 9.0 +/- 7.6
      vs. 16.7 +/- 37.3%). Consequently, basal ACTH was (100.9 +/- 85.0 vs. 138.0 +/-
      123.7 vs. 4.8 +/- 4.3 pg/mL) and maximal stimulated ACTH (203.8 +/- 160.1 vs.
      288.0 +/- 189.5 vs. 7.4 +/- 9.2 pg/mL). For cortisol, determination area under
      ROC curve was 0.815 +/- 0.083 (CI 95% 0.652-0.978). For cortisol increase cut-off
      level of 20%, test sensitivity was 83%, with specificity of 78%. For ACTH,
      determination area under ROC curve was 0.637 +/- 0.142 (CI 95% 0.359-0.916). For
      ACTH increase cut-off level of 30%, test sensitivity was 70%, with specificity of
      57%. CONCLUSION: Determination of cortisol and ACTH levels in CRH test remains
      reliable tool in differential diagnosis of Cushing's syndrome.

PMID- 17503566
TI  - [Tubular kidney function in patients with type 2 diabetes mellitus,
      microalbuminuria and proteinuria].
AB  - INTRODUCTION: Diabetes mellitus (DM) and hypertension are the most frequent
      causes of kidney function damage. Many different tests are developed to detect
      reversible functional kidney changes (detection of microalbuminuria and selective
      urinary enzymes). OBJECTIVE: The aim of our study was to examine tubular kidney
      function in type 2 DM patients with different proteinuria levels, and to compare
      these results with healthy people. METHOD: The patients with type 2 DM and
      creatinine clearance >80 ml/min were included in the study. According to the
      levels of proteinuria, the patients were classified in three groups: group I-
      patients with proteinuria <300 mg/24 h, and no microalbuminuria; group II--the
      patients with proteinuria <300 mg/24 h and microalbuminuria >20 mg/24 h; and
      group III--the patients with proteinuria >300 mg/24 h. The control group
      consisted of healthy subjects. RESULTS: The study revealed that in type 2 DM
      patients and normal global kidney function, fractional excretions of sodium,
      potassium, and phosphates as well as renal phosphate concentrations were not
      adequately sensitive markers to detect damage in tubular kidney function in DM.
      There were some changes of urate fractional excretion in these patients: this
      value was significantly lower in patients with microalbuminuria compared with
      those with proteinuria >300 mg/24 h, as well as in the control group (p < 0.05).
      Hormone dependent tubular kidney activity, urinary osmolarity, and urea
      fractional excretion in all patients were within normal ranges. CONCLUSION: It is
      evident that routine laboratory analyses are not sensitive markers to detect
      early changes of kidney function in type 2 DM.

PMID- 17503567
TI  - [The expression of p53 protein in patients with multiple myeloma].
AB  - INTRODUCTION: Although mutations of p53 are one of the most often acquired
      genetic changes in malignant tumors, these mutations are rare events in patients
      with newly diagnosed multiple myeloma (MM). Moreover, there are a few literature
      data about clinical significance of p53 overexpression in multiple myeloma.
      OBJECTIVE: The aim of our study was to evaluate the clinical significance of p53
      immunoexpression in multiple myeloma. METHOD: A total of 58 patients with newly
      diagnosed MM (26 females and 32 males, mean age 62 years) were enrolled in the
      study. The diagnosis of MM was made according to criteria of Chronic Leukemia
      Myeloma Task Force. Clinical staging was done according to Durie and Salmon
      classification (4 patients had disease stage 1, 15 patients stage II and 39
      patients stage III). The histological grade and histological stage were
      determined according to predominant plasma cell morphology and volume of myeloma
      infiltration, respectively. Standard immunohistochemical analysis with p53
      antibody in B5-fixed and paraffin-embedded bone marrow specimens was used to
      evaluate the expression of p53 in myeloma cells. The specimens were considered
      positive when 25% of plasma cells exhibited clear nuclear positivity. RESULTS:
      Out of 58 patients, p53 expression was detected in 9 (15.52%). No significant
      correlation was found between p53 expression and clinical stage (I+II vs. III),
      beta2-microglobulin level (< or =6 mg/L vs. > 6 mg/L), histological grade (I vs.
      II+III), histological stage (<20% vs. 21-50% vs. >50%) and the extent of
      osteolytic lesions (< or =3 vs. >3 lesions). Median survival of patients with p53
      immunoreactivity in =>5% of plasma cells was 10 months, whilst median survival of
      patients with p53 immunoreactivity in <5% of plasma cells was 36 months. However,
      such difference was not significant (p = 0.2). CONCLUSION: The frequency of p53
      immunoexpression in our group of newly diagnosed MM was relatively low. Although
      p53 immunoexpression was not associated with clinical and histological features
      of more aggressive disease, or with shorter survival, further investigations of
      larger group of patients will lead to final conclusions.

PMID- 17503568
TI  - [The evaluation of hemodialysis adequacy during the use of different dialysis
      membranes].
AB  - INTRODUCTION: Hemodialysis efficacy that significantly influences morbidity and
      mortality of patients can be evaluated by different widely used indices of
      adequacy. OBJECTIVE: The aim of the study was to evaluate the adequacy of
      hemodialysis in the group of patients on maintenance hemodialysis and to examine
      the influence of different dialysis membranes on the indices of adequacy and
      frequency of symptoms and complications developing during dialysis treatment.
      METHOD: The study involved 14 patients dialyzed in three successive months with
      three different types of dialyzers: E3 (Hemomed)--cuprophane membrane, 1.3 m2, F6
      (Hemomed)--polysulfone membrane, 1.3 m2, CM23 (Zdravlje)--cuprophane membrane,
      1.25 m2. Each type of dialyzers was used during one month, meaning during 12
      successive 4-hour hemodialyses. RESULTS: Mean value of Kt/V index was 1.39 +/-
      0.21 for E3 dialyzer, 1.18 +/- 0.24 for F6 dialyzer and 1.44 +/- 0.25 for CM23
      dialyzer. The difference between the indices was statistically significant (p <
      0.05). Mean protein catabolic rate (PCRn) ranged between 1.6 and 1.7 and no
      significant difference was found between the dialyzers used. The frequency of
      hypertension episodes was similar during the hemodialysis with different
      dialyzers, but the incidence of different symptoms and hypotension episodes was
      significantly lower during hemodialysis with polysulfone membrane. CONCLUSION:
      Hemodialysis with three examined types of dialyzers enabled acceptable dialysis
      adequacy. Dialyzers with cuprophane membrane enabled significantly higher Kt/V
      index, but the incidence of symptoms and hypotension was significantly lower
      during hemodialysis with polysulfone membrane.

PMID- 17503569
TI  - [Factors influencing the development of avascular necrosis in non-operative
      treatment of the acute slipped capital femoral epiphysis].
AB  - INTRODUCTION: The acute slipped capital femoral epiphysis can result in
      development of avascular necrosis of the femoral head which is very difficult
      condition to treat. Orthopedic surgeon can influence the development of avascular
      necrosis. OBJECTIVE: The main objective in our study was to identify factors
      influencing the development of avascular necrosis in nonoperative treated
      patients for the acute slipped capital femoral epiphysis. METHOD: A total of 53
      patients and 59 hips treated for the acute slipped capital femoral epiphysis at
      the Institute for Orthopedic Surgery,Banjica" between 1968-2004 were studied.
      Necessary data were obtained from the accurate medical records. RESULTS:
      Avascular necrosis of the femoral head was diagnosed in 8 patients (13.56%). Six
      of them (75%) were treated by manipulative reduction in general anesthesia and
      spica cast immobilization. Fischer test, used for statistical data processing,
      found significant difference between two non-operative methods of treatment (p =
      0.0008). CONCLUSION: Higher-degree epihyseal displacement as well as complete
      separation of the physis and metaphysis were found to be the risk factors of
      avascular necrosis. Every manipulation with the affected hip was also associated
      with higher percentage of avascular necrosis of the femoral head.

PMID- 17503570
TI  - [Factors mediating the depression in the adult obese outpatients].
AB  - INTRODUCTION: The prevalence of obesity is rising to epidemic proportions at the
      alarming rate in both developed and underdeveloped countries around the world.
      Current prevalence data from individual national studies suggest that the obesity
      prevalence in the European countries ranges from 10% to 20% for men, and 10% to
      25% for women. Health consequences of obesity imply both a number of fatal and
      non-fatal health problems (out of which the most common are cardiovascular
      problems, non-insulin dependent diabetes mellitus, cancers), and also a wide
      spectrum of psychological consequences from diminished self-esteem to clinical
      depression. Causal relationship between obesity and many chronic diseases is
      evidence-based. At the same time, there are marked differences in research data
      regarding causal obesity-depression relationship. Several studies have found no
      direct association between obesity and depression, while in others the prevalence
      of depression in obese patients was up to 50%. Gender, obesity grade,
      socioeconomic status and asking for professional help are named as moderators and
      mediators of this relationship. Among recommended screening methods, BDI-II is
      the most frequently used in the adult outpatient departments. OBJECTIVE: The aim
      of the study was to determine possible risk factors of depression in adult obese
      patients treated for obesity. Gender, obesity and education level as well as
      marital status were analyzed as possible moderators of depression-obesity
      relationship. METHOD: The research included 267 patients, 38.0 +/- 14.6 years of
      age, who referred to the Outpatient Nutrition Department for dietetic
      consultation or nutritional medical therapy. Nutritional status was assessed by
      BMI (kg/m2), calculated from measured values of body weight and height according
      to WHO recommendations. An estimate of the existence and/or depression level was
      investigated by Beck Depression Inventory--self-administered questionnaire
      recommended for use in Serbian population. RESULTS: The results revealed higher
      average BDI score values in obese patients (F(267,1) = 6.014, p = 0.015) in
      comparison to their non-obese counterparts. In addition, the percentage of
      depressive obese patients was significantly higher (55.1%, chi2(267.1) = 22.64, p
      < 0.001). There was significant correlation of BMI and BDI scores (r = 0.246, p <
      0.001). The number of women with depression was significantly higher in
      comparison to men (chi2(267.1) = 4.261, p = 0.039). Women also had higher average
      BDI score (p = 0.003). MANOVA showed that BDI score was influenced by gender
      (F(267.1) = 8.936, p = 0.030) and nutritional status (F(267.1) = 6.115, p =
      0.014), but combined effect of the above-mentioned moderators was not
      significant. CONCLUSION: Depression is ten times more frequent in obese patients
      undergoing the obesity treatment vs. general population and, therefore, screening
      for depression is needed. Special attention should be paid to women and more
      obese patients due to higher incidence of depression in these groups.

PMID- 17503571
TI  - [Malignant diseases in medicolegal practice].
AB  - INTRODUCTION: In many cases of natural death (so-called obscure natural death),
      medicolegal assessment and elucidation are required. Although malignant tumors
      may be the cause of obscure natural death, their forensic significance has not
      been particularly studied in our population. OBJECTIVE: The objective of the
      study was to provide a general report on medicolegal importance of malignant
      diseases. METHOD: Autopsy material of the Institute of Forensic Medicine,
      Belgrade, from 1990 to 2000, was analyzed. The data were obtained from autopsy
      records, investigation reports, family members of the deceased and available
      medical documentation. RESULTS: The malignant tumor was the cause of death in 81
      cases (0.69% out of a total of 11771 autopsies), in 52 males and 29 females,
      respectively. The incidence of malignant diseases increased with age. The most
      frequent cause of death was the lung cancer--diagnosed in 33 cases (40.7% out of
      81), with somewhat higher percentage in females (41.4%) than in males (40.4%),
      but this difference was not statistically significant (chi2 = 0.13; p > 0.05).
      Other locations of malignancies were less frequently found: brain (7 cases),
      colon (6), stomach (5) and pancreas (4). In 67 cases, widespread tumor with
      metastases was identified as an immediate cause of death, in 8 cases there was a
      hemorrhage from eroded blood vessels, and in 6 cases peritonitis due to gastric
      or intestinal leakage into the abdominal cavity at the site of wall perforation.
      In 61.7% cases, fatal tumor was not diagnosed during the life, and was recorded
      more frequently in female group (75.9%) than in males (53.8%), but this
      difference was not statistically significant (chi2 = 2.71; p > 0.05). In most
      cases of lung cancer (22 or 66.7% out of 33), which was predominant type in the
      analyzed sample, malignancy remained unrecognized during the life. CONCLUSION:
      The most important medicolegal problems regarding fatal malignant diseases are
      associated with exclusion of violent death in cases that are characterized as
      obscure (suspicious) natural death, as well as assessment of possible legal
      responsibility of medical staff in cases in which malignant tumor has not been
      diagnosed during the life.

PMID- 17503572
TI  - [Forensic expertise of the injury severity in fatally injuried car-occupants].
AB  - INTRODUCTION: There is no specific injury among fatally injured frontal car
      occupants in frontal car collisions, used in forensic expertise. We tried to
      point out the usefulness of the Abbreviated Injury Scale (AIS) and Injury
      Severity Score (ISS) for the expertise in such cases. OBJECTIVE: Analyzing the
      severity of body region injuries and total injury severity of deceased car
      occupants, to point out their importance in forensic expertise. METHOD:
      Retrospective autopsy study was performed. Autopsy records of all deceased car
      occupants in frontal car collisions were analyzed in order to establish the
      severity of injuries in body regions (AIS) and total severity of injuries (ISS).
      Statistical analysis was performed using the chi-square test, t-test, and
      logistic regression, with significance set at p < 0.05. RESULTS: A total of 500
      cases were analyzed: 282 car-drivers and 218 front car-passengers, average age of
      41.48 +/- 15.31 and 39.78 +/- 16.93. There were 401 males and 99 females. The
      most injured body region was head with neck: AIS = 3.50 +/- 2.48, for car
      drivers, and AIS = 3.54 +/- 2.50, for front car-passengers, as well as thorax:
      AIS = 3.63 +/- 2.16 car-drivers, and AIS = 3.37 +/- 2.14, for front car
      passengers. More severe injuries of head (AIS > or =4) suggested that deceased
      was a front car-passenger (Wald = 13.27; p = 0.04). More severe injuries of
      thorax and abdomen (AIS > or =5) indicated that deceased was a car-driver (Wald =
      5.72; p = 0.02, and Wald = 8.23; p = 0.01, respectively). The injury severity of
      the face and limbs were useless in such expertise (Wald = 1.72; p = 0.19, and
      Wald =0.89; p = 0.34, respectively). An average ISS was 57.31 +/- 20.16 for car
      drivers, and 54.54 +/- 21.01 for front car-passengers. The ISS value was useless
      in expertise (t=1.50; p = 0.13, and Wald = 2.24; p = 0.13). CONCLUSION: As the
      injury of the head is more severe, the deceased is more likely to be the front
      car-passenger. Severe thoracic and abdominal injuries are more characteristic for
      car-drivers. A total injury severity is useless for forensic expertise in cases
      of fatally injured in car collisions.

PMID- 17503573
TI  - [Enteropathy associated T-cell lymphoma].
AB  - Enteropathy associated T-cell lymphoma (EATCL) is a high grade, pleomorphic
      peripheral T-cell lymphoma with usually cytotoxic phenotype. This is a case
      report of three patients with EATCL. The first patient was 50 year-old woman with
      four-year history of gluten sensitive enteropathy (GSE). Diagnosis of lymphoma
      was confirmed after the resection of the jejunum (small intestine obstruction).
      Pathohistological (PAS, Reticulin, Giemsa) and immunohistochemical (anti-LCA,
      anti-CD20, anti-CD45RO, anti-CD3) methods revealed the diagnosis of EATCL:
      CD45RO+, CD3+. After the third cycle of chemotherapy, the disease progressed with
      massive lung infiltration. Patient died due to complications of bone marrow
      aplasia. The second patient was 23 year-old woman with long earlier history of
      GSE. She presented with the acute renal failure. According to established
      diagnosis of tubulointerstitial nephritis, she was treated with pulse doses of
      steroid therapy. After temporary improvement, she had dissemination of the
      disease. On MRI, small intestinal wall was thickened, and abdominal lymph nodes
      were enlarged with extraluminal compression of common bile duct. Laparotomy with
      mesenterial lymph node biopsy and consecutive pathohistological and
      immunohistochemical analyses revealed the diagnosis of EATCL. The patient
      received chemotherapy, but she died with signs of pulmonary embolization. The
      third patient was 53 year-old woman without previous history of GSE. Diagnosis of
      EATCL was revealed after the resection of jejunum because of small intestinal
      obstruction. She received two cycles of chemotherapy, but she died with signs of
      disease progression. IgA antiendomysial antibodies were detected in the serum of
      all patients. The overall survival of patients was 7 months.The possibility of
      lymphoma rising in patients with clinical progression of GSE despite gluten free
      diet must be kept in mind.

PMID- 17503574
TI  - [Intrapartal resection of the bicornuete uterus for placenta membranacea
      percreta].
AB  - Placenta membranacea is a rare anomaly characterized by failure of villous
      atrophy during early gestation, and 30% of cases involve some form of placental
      adherence. Placenta percreta is infrequent, but life-threatening condition.
      Antenatal diagnosis of these placental anomalies is very difficult, but essential
      for reduction of the number and extent of possible complications. A 19-year-old
      primigravida was referred to us with 31-week pregnancy complicated by
      preeclampsia. Upon admission, ultrasound scan revealed eutrophic fetus in breech
      presentation, without any signs of retroplacental clot. At laparotomy,
      hemoperitoneum without any trophoblastic tissue emerging to the peritoneal cavity
      was found and placental abruption with uteroplacental apoplexy was suspected. In
      addition, unicervical symmetric bicornuate uterus with pregnancy in the left
      uterine horn was found. The lower segment uterine section was performed and 1800
      grams live baby was delivered. Delivery of the placenta was unusually difficult.
      It was very large and densely adherent to the posterior uterine wall, which
      appeared to be composed of serosa in that area only. After removal of placenta,
      the hemorrhage could not be controlled, and resection of the left uterine horn
      was performed. Placenta accreta, increta and percreta ought to be considered in
      all cases of uterine anomalies in pregnancy and in cases of prenatal diagnosis of
      placenta membranacea.

PMID- 17503575
TI  - [Chylopericardium as a complication of cardiac surgery: report of two cases and
      review of the literature].
AB  - Chylopericardium refers to existing communication between the pericardial sac and
      the thoracic duct carrying the chyle. The objective of our report was to
      highlight the specificity of diagnosis and treatment of this rare but tedious
      condition through the analysis of two case reports. Male patient, aged 63 years,
      with chylopericardium was diagnosed perioperatively (implantation of artificial
      aortic--St. Jude No 21 and mitral valve--St. Jude No 29). Etiology of pericardial
      effusion was established by Sudan III staining of punctate specimen obtained by
      subxiphoid pericardial puncture. Probable cause of chylopericardium was the
      lesion of ductus thoracicus during cross-clamping of the superior caval vein with
      a Cooley clamp. Initial treatment included diet rich in medium-chain
      triglycerides which resulted in resolution of the effusion. During five-year
      follow-up, there were no recurrences of pericardial effusion. The second patient
      was female, 21 years old, with chylopericardium after partial pericardiectomy
      performed because of the chronic severely symptomatic pericardial effusion,
      resistant to other forms of treatment. Pericardiocentesis provided 650 ml of
      yellowish fluid with a high concentration of cholesterol (3.2 mmol/l),
      triglycerides (16.6 mmol/l), and proteins (64.7 g/l), which verified
      chylopericardium, most probably as a consequence of the lesion of ductus
      thoracicus during partial pericardiectomy. Diet rich in medium-chain
      triglycerides failed to decrease the effusion, after two weeks of treatment
      (daily secretion 250-350 ml). Lymphography revealed lesion of ductus thoracicus,
      most probably at Th9/Th10 level, with no direct visualization of extravasal
      accumulation of contrast media. Surgical ligation of ductus thoracicus was
      performed through the right thoracotomy. However, postoperative secretion
      increased to 1000 ml/day. Patient underwent redo surgery comprising the ligation
      of lymphatic vessels, guided by extravasation of intraoperatively iwected
      methylene-blue indicator. During one-year follow-up, there were no recurrences of
      pericardial effusion. In conclusion, intraoperative lymphography significantly
      contributed to successful surgical treatment of patients with chylopericardium.

PMID- 17503576
TI  - [New indications for transcranial Doppler--huge steps forward].
AB  - Huge steps forward in understanding and treatment of ischemic stroke happened in
      the last several decades. Significant part of this progress is due to advances in
      diagnostic possibilities, with the leading role of transcranial Doppler (TCD).
      The American Academy of Neurology has recently published new guidelines and
      indications for TCD use. Indications with the highest rank, when TCD is able to
      provide information with established clinical utility, are designated as follows:
      (1) screening of children aged 2 to 16 years with sickle cell disease for
      assessing the stroke risk, and (2) detection and monitoring of vasospasm in
      spontaneous subarachnoid hemorrhage. TCD indications in setting where this
      examination provides important information but with still indefinite clinical
      utility are: (1) intracranial steno-occlusive disease, with data insufficient to
      recommend replacement of conventional angiography with TCD, despite obvious TCD
      usefulness and precision, and (2) cerebral circulatory arrest detection, as
      confirmatory test in support of clinical diagnosis of brain death. The major
      limiting factor of TCD application is dependence on an examiner's training and
      skills. Only strict application of diagnostic protocols and accepted criteria,
      with knowledge of pathophysiologic basis of cerebrovascular diseases and TCD
      principles, can result in conclusive findings. TCD is the source of valuable
      information for neurologists and other specialty physicians. This text presents
      review of other TCD indications and their application in everyday practice.

PMID- 17503577
TI  - [Hepatorenal syndrome].
AB  - Hepatorenal syndrome is complication of the advanced cirrhosis characterized by
      functional renal failure and changes of systemic blood pressure due to increased
      activity of endogenous vasoactive systems. Functional renal failure is due to
      severe renal cortical ischemia and reduction of glomerular filtration rate (GFR)
      developing in the late stages of cirrhosis. The pathogenesis of hepatorenal
      syndrome is the result of an extreme underfilling of the arterial circulation
      secondary to arterial vasodilatation located in the splanchnic circulation.
      Reduced effective arterial blood volume triggers a compensatory response with
      activation of systemic and renal vasoconstrictor systems. At the same time, the
      ascites becomes refractory in some patients, as it is no longer responsive to
      diuretic treatment. These changes result from combination of deteriorating liver
      function and increasing portal pressure, further splanchnic vasodilatation,
      increase of circulating vasoconstrictors, and decrease of renal blood flow and
      GFR. Hepatorenal syndrome can be precipitated by shock, infection, nephrotoxic
      drugs, bleeding, surgery or large volume paracentesis. Renal failure may be
      rapidly progressive (type I HRS) or may develop more slowly (type II HRS), which
      is usually associated with refractory ascites. The diagnosis of HRS is based on
      established diagnostic criteria aimed at excluding the nonfunctional causes of
      renal failure. The prognosis of patients with HRS is very poor. Liver
      transplantation remains the only curative treatment for the time being.
      Pharmacological therapies based on the use of vasoconstrictor drugs may serve as
      a bridge to liver transplantation. Prevention of HRS by albumin infusion is
      recommended in patients with spontaneous bacterial peritonitis and by
      pentoxifylline in patients with the acute alcoholic hepatitis.

PMID- 17503578
TI  - [Complications of slipped capital femoral epiphysis].
AB  - Slipped capital femoral epiphysis is well known disorder of the hip in
      adolescents, which is characterized by displacement of the capital femoral
      epiphysis from the metaphysis through the physeal plate. The incidence of slipped
      capital femoral epiphysis is about 5-8 cases per 100,000 adolescents. Etiology of
      slipped capital femoral epiphysis is still unknown, but this disorder is probably
      combination of genetic, hormonal and mechanical factors. On the basis of
      patient's history, physical examination, and radiographs, slipped capital femoral
      epiphysis can be classified as acute or chronic. Two most severe complications of
      slipped capital femoral epiphysis are avascular necrosis and chondrolysis.
      Avascular necrosis is more commonly associated with the acute slips when the
      lateral epiphyseal vessels are disrupted. In chronic slips, avascular necrosis
      can occur as a result of treatment. Chondrolysis or cartilage necrosis can occur
      in untreated slips, but is often associated with spica cast imobilization or
      penetratation of the internal fixation screws into the joint space. The final
      outcome of avascular necrosis and chondrolysis is extremly poor for a patient.
      Therefore, the baseline of management of slipped capital femoral epiphysis is
      treatment by adequate techniques that have high rate of success with minimal risk
      of complications.

PMID- 17503579
TI  - [History of pediatric anesthesiology].
AB  - Among advances in medicine during the past 150 years, certainly the introduction
      of surgical anesthesia must be considered the greatest gifts of medical
      profession to mankind, especially to children. Pediatric anesthesia has
      progressed rapidly throughout the years. Since the first recorded case of
      pediatric anesthesia in 1842 to the latest advancement in training, technology,
      medicine and equipment in the last decades of this century, many historic moments
      have been following each other. Throughout the first decades of 20th century,
      most physicians treated children as miniature adults. It is believed that the
      development of modern pediatric anesthesia started in 1930. To offer a historic
      perspective, the evolution of new field through its rapid growth was divided into
      two chronologic categories: first (1930-1950) and second (1950-present). During
      the first period (1930-1950), the anesthesia techniques and equipment adjusted to
      different children's age were developed. In the second, together with further
      technique and equipment refinement, modern anesthetics and vital system
      surveillance (monitoring) were introduced into everyday practice. The keyto the
      advances in pediatric anesthesiology was difficulties leading to new inventions
      with consequent improvement of techniques and methods. This article reviews the
      origins and development of anesthesia for infants and children in the world and
      Serbia, emphasizing the contributions of many devoted physicians that represented
      the major force leading to inevitable evolution of pediatric anesthesia.

PMID- 17503580
TI  - Diversity and host range of foliar fungal endophytes: are tropical leaves
      biodiversity hotspots?
AB  - Fungal endophytes are found in asymptomatic photosynthetic tissues of all major
      lineages of land plants. The ubiquity of these cryptic symbionts is clear, but
      the scale of their diversity, host range, and geographic distributions are
      unknown. To explore the putative hyperdiversity of tropical leaf endophytes, we
      compared endophyte communities along a broad latitudinal gradient from the
      Canadian arctic to the lowland tropical forest of central Panama. Here, we use
      molecular sequence data from 1403 endophyte strains to show that endophytes
      increase in incidence, diversity, and host breadth from arctic to tropical sites.
      Endophyte communities from higher latitudes are characterized by relatively few
      species from many different classes of Ascomycota, whereas tropical endophyte
      assemblages are dominated by a small number of classes with a very large number
      of endophytic species. The most easily cultivated endophytes from tropical plants
      have wide host ranges, but communities are dominated by a large number of rare
      species whose host range is unclear. Even when only the most easily cultured
      species are considered, leaves of tropical trees represent hotspots of fungal
      species diversity, containing numerous species not yet recovered from other
      biomes. The challenge remains to recover and identify those elusive and rarely
      cultured taxa with narrower host ranges, and to elucidate the ecological roles of
      these little-known symbionts in tropical forests.

PMID- 17503581
TI  - Ecological implications of anti-pathogen effects of tropical fungal endophytes
      and mycorrhizae.
AB  - We discuss studies of foliar endophytic fungi (FEF) and arbuscular mycorrhizal
      fungi (AMF) associated with Theobroma cacao in Panama. Direct, experimentally
      controlled comparisons of endophyte free (E-) and endophyte containing (E+) plant
      tissues in T. cacao show that foliar endophytes (FEF) that commonly occur in
      healthy host leaves enhance host defenses against foliar damage due to the
      pathogen (Phytophthora palmivora). Similarly, root inoculations with commonly
      occurring AMF also reduce foliar damage due to the same pathogen. These results
      suggest that endophytic fungi can play a potentially important mutualistic role
      by augmenting host defensive responses against pathogens. There are two broad
      classes of potential mechanisms by which endophytes could contribute to host
      protection: (1) inducing or increasing the expression of intrinsic host defense
      mechanisms and (2) providing additional sources of defense, extrinsic to those of
      the host (e.g., endophyte-based chemical antibiosis). The degree to which either
      of these mechanisms predominates holds distinct consequences for the evolutionary
      ecology of host-endophyte-pathogen relationships. More generally, the growing
      recognition that plants are composed of a mosaic of plant and fungal tissues
      holds a series of implications for the study of plant defense, physiology, and
      genetics.

PMID- 17503582
TI  - Distinct mycorrhizal communities on new and established hosts in a transitional
      tropical plant community.
AB  - The extent to which interspecific plants share mycorrhizal fungal communities
      depends on the specificity of the symbiosis. For tropical forest tree seedlings,
      colonization by mycorrhizal fungi associated with established vegetation could
      have important consequences for survival and growth. I used a novel molecular
      technique to assess the potential for sharing of mycorrhizas in forest and
      pasture in southern Costa Rica, by identifying arbuscular mycorrhizal (AM) fungi
      in roots of the forest canopy tree species Terminalia amazonia, pasture grasses
      Urochloa ruziziensis and U. decumbens, and seedlings of T. amazonia planted into
      experimental reforestation plots. I tested the hypotheses that experimental
      seedlings were colonized either by the AM fungal community of the forest T.
      amazonia (suggesting host specificity) or of Urochloa (suggesting absence of
      specificity/importance of local environment). After two years, pasture-grown T.
      amazonia seedlings were colonized by neither community, but rather by a species
      of Glomus that was rarely observed on the other plants. These results suggest
      that conspecific seedlings planted into existing vegetation generate a distinct
      mycorrhizal community that may influence competitive interactions and the
      relative costs and benefits of the AM fungal symbiosis at early stages in the
      life cycle of tropical trees.

PMID- 17503583
TI  - Common ectomycorrhizal networks may maintain monodominance in a tropical rain
      forest.
AB  - Most tropical rain forests contain diverse arrays of tree species that form
      arbuscular mycorrhizae. In contrast, the less common monodominant rain forests,
      in which one tree species comprises more than 50% of the canopy, frequently
      contain ectomycorrhizal (ECM) associates. In this study, I explored the potential
      for common ECM networks, created by aggregations of ECM trees, to enhance
      seedling survivorship near parent trees. I determined the benefit conferred by
      the common ECM network on seedling growth and survivorship of an ECM monodominant
      species in Guyana. Seedlings with access to an ECM network had greater growth
      (73% greater), leaf number (55% more), and survivorship (47% greater) than
      seedlings without such access, suggesting that the ECM network provides a
      survivorship advantage. A survey of wild seedlings showed positive distance
      dependent distribution and survival with respect to conspecific adults. These
      experimental and survey results suggest that the negative distance-dependent
      mechanisms at the seedling stage thought to maintain tropical rain forest
      diversity are reversed for ECM seedlings, which experience positive feedbacks
      from the ECM network. These results may in part explain the local monodominance
      of an ECM tree species within the matrix of high-diversity, tropical rain forest.

PMID- 17503584
TI  - The patchiness of epifoliar fungi in tropical forests: host range, host
      abundance, and environment.
AB  - Fungal symbioses affect the diversity, dynamics, and spatial patterns of trees in
      tropical forests. Their ecological importance is partly driven by their inherent
      patchiness. We used epifoliar fungi, a guild of common, benign, obligate, fungal
      symbionts of plants, as a model system to evaluate the relative importance of
      host phylogeny, host relative abundance, and microclimate on the three
      dimensional distribution of plant-fungus symbioses. In parallel studies in
      rainforests in Panama and Australia, most epifoliar fungi were able to colonize
      several plant lineages but showed significant host preferences within the local
      plant community. More closely related plant species were not more likely to share
      fungal symbionts. Instead, fungal species were more likely to be shared by more
      abundant hosts, which supported a greater number and diversity of fungi.
      Environmental conditions strongly affected spatial distributions, with sites in
      the dark understory 2.5- to fourfold more likely to have epifoliar fungi than in
      the exposed forest canopy. In the understory, fungal incidence increased with
      canopy openness. Canopy trees supported only a subset of the fungal symbionts
      found in the understory, suggesting that adult trees are not reservoirs of these
      fungal symbionts for understory juveniles.

PMID- 17503585
TI  - Diversity, host affinity, and distribution of seed-infecting fungi: a case study
      with Cecropia.
AB  - Recruitment limitation has been proposed as an important mechanism contributing
      to the maintenance of tropical tree diversity. For pioneer species, infection by
      fungi significantly reduces seed survival in soil, potentially influencing both
      recruitment success and adult distributions. We examined fresh seeds of four
      sympatric Cecropia species for evidence of fungal infection, buried seeds for
      five months in common gardens below four C. insignis crowns in central Panama,
      and measured seed survival and fungal infection of inviable seeds. Seed survival
      varied significantly among species and burial sites, and with regard to local
      (Panama) vs. foreign (Costa Rica) maternal seed sources. Fresh seeds contained
      few cultivable fungi, but > 80% of soil-incubated seeds were infected by diverse
      Ascomycota, including putative pathogens, saprophytes, and endophytes. From 220
      isolates sequenced for the nuclear internal transcribed spacer region (ITS), 26
      of 73 unique genotypes were encountered more than once. Based on the most common
      genotypes, fungal communities demonstrate host affinity and are structured at the
      scale of individual crowns. Similarity among fungal communities beneath a given
      crown was significantly greater than similarity among isolates found under
      different crowns. However, the frequency of rare species suggests high fungal
      diversity and fine-scale spatial heterogeneity. These results reveal complex
      plant-fungal interactions in soil and provide a first indication of how seed
      survival in tropical forests may be affected by fungal community composition.

PMID- 17503586
TI  - Life-history strategies of plant pathogens: distribution patterns and
      phylogenetic analysis.
AB  - Here we analyze herbarium records, surveys, and studies of fungal plant pathogens
      in tropical natural systems in order to establish a framework to study plant
      pathogen interactions from a life-history perspective. We looked at how life
      history traits of pathogens and their host plants affect the distribution of
      pathogens in different tropical habitats, and the importance of host phylogeny in
      determining the habitat associations of obligate fungal pathogens. Our study
      reveals that plant-pathogen interactions are prevalent and widespread in the
      tropics. Phylogenetic analysis of the distribution of obligate pathogens among
      plant families did not suggest a strong overall pattern of higher-level host
      phylogeny in pathogen host range, except that smut pathogens are particularly
      dominant on Poaceae and Asteraceae, and rusts are most common on Fabaceae,
      families that dominate disturbed areas in the tropics.

PMID- 17503587
TI  - Can we measure carrying capacity with foraging behavior?
AB  - Carrying capacity is one of the most important, yet least understood and rarely
      estimated, parameters in population management and modeling. A simple behavioral
      metric of carrying capacity would advance theory, conservation, and management of
      biological populations. Such a metric should be possible because behavior is
      finely attuned to variation in environment including population density. We
      connect optimal foraging theory with population dynamics and life history to
      develop a simple model that predicts this sort of adaptive density-dependent
      change in food consumption. We then confirm the model's unexpected and manifold
      predictions with field experiments. The theory predicts reproductive thresholds
      that alter the marginal value of energy as well as the value of time. Both
      effects cause a pronounced discontinuity in quitting-harvest rate that we
      revealed with foraging experiments. Red-backed voles maintained across a range of
      high densities foraged at a lower density-dependent rate than the same animals
      exposed to low-density treatments. The change in harvest rate is diagnostic of
      populations that exceed their carrying capacity. Ecologists, conservation
      biologists, and wildlife managers may thus be able to use simple and efficient
      foraging experiments to estimate carrying capacity and habitat quality.

PMID- 17503588
TI  - Direct and indirect effects of climate and habitat factors on butterfly
      diversity.
AB  - Many factors, including climate, resource availability, and habitat diversity,
      have been proposed as determinants of global diversity, but the links among them
      have rarely been studied. Using structural equation modeling (SEM), we
      investigated direct and indirect effects of climate variables, host-plant
      richness, and habitat diversity on butterfly species richness across Britain, at
      20-km grid resolution. These factors were all important determinants of butterfly
      diversity, but their relative contributions differed between habitat generalists
      and specialists, and whether the effects were direct or indirect. Climate
      variables had strong effects on habitat generalists, whereas host-plant richness
      and habitat diversity contributed relatively more for habitat specialists.
      Considering total effects (direct and indirect together), climate variables had
      the strongest link to butterfly species richness for all groups of species. The
      results suggest that different mechanistic hypotheses to explain species richness
      may be more appropriate for habitat generalists and specialists, with generalists
      hypothesized to show direct physiological limitations and specialists
      additionally being constrained by trophic interactions (climate affecting host
      plant richness).

PMID- 17503589
TI  - Trophic levels and trophic tangles: the prevalence of omnivory in real food webs.
AB  - The concept of trophic levels is one of the oldest in ecology and informs our
      understanding of energy flow and top-down control within food webs, but it has
      been criticized for ignoring omnivory. We tested whether trophic levels were
      apparent in 58 real food webs in four habitat types by examining patterns of
      trophic position. A large proportion of taxa (64.4%) occupied integer trophic
      positions, suggesting that discrete trophic levels do exist. Importantly however,
      the majority of those trophic positions were aggregated around integer values of
      0 and 1, representing plants and herbivores. For the majority of the real food
      webs considered here, secondary consumers were no more likely to occupy an
      integer trophic position than in randomized food webs. This means that, above the
      herbivore trophic level, food webs are better characterized as a tangled web of
      omnivores. Omnivory was most common in marine systems, rarest in streams, and
      intermediate in lakes and terrestrial food webs. Trophic-level-based concepts
      such as trophic cascades may apply to systems with short food chains, but they
      become less valid as food chains lengthen.

PMID- 17503590
TI  - Grass shrimp (Palaemonetes spp.) play a pivotal trophic role in enhancing Ruppia
      maritima.
AB  - Coupled trophic-engineer interactions are potentially important for maintaining
      habitat function and ecosystem services. As ephemeral submerged aquatic
      vegetation (SAV), Ruppia maritima has a short well-defined growth-senescence
      cycle and should benefit from any ecological interaction that enhances its
      physical condition and longevity. Grass shrimp (Palaemonetes spp.) are abundant
      facultative grazers of epiphytic algae and conveyors of nutrients in tidal marsh
      and SAV habitats. Grass shrimp addition consistently enhanced Ruppia biomass and
      shoot density in a series of three field experiments conducted in Grand Bay
      National Estuarine Research Reserve, Mississippi, USA. In two experiments,
      epiphyte grazing by grass shrimp enhanced Ruppia by inhibiting die-back during
      the mid- and latter stages of the Ruppia life cycle. Despite a nonsignificant
      epiphyte grazing effect, grass shrimp also enhanced Ruppia during its early
      growth stage in a third experiment. In that experiment, nutrient addition also
      significantly increased epiphyte biomass. Grass shrimp may have fostered the
      early growth of Ruppia through direct deposition of feces to the sediment in the
      third experiment. Grass shrimp play a pivotal trophic role in the maintenance of
      Ruppia through context-dependent interactions involving stage of the SAV life
      cycle, season, and nutrient limitation.

PMID- 17503591
TI  - Density dependence and density independence during the early life stages of four
      marine fish stocks.
AB  - Recruitment variability caused by density-dependent and density-independent
      processes is an important area within the study of fish dynamics. These processes
      can exhibit nonlinearities and nonadditive properties that may have profound
      dynamic effects. We investigate the importance of population density (i.e.,
      density dependence) and environmental forcing (i.e., density independence) on the
      age-0 and age-1 abundance of capelin (Mallotus villosus), northeast Arctic cod
      (Gadus morhua), northeast Arctic haddock (Melanogrammus aeglefinus), and
      Norwegian spring spawning herring (Clupea harengus) in the Barents Sea. We use
      statistical methods that explicitly account for nonlinearities and nonadditive
      interactions between internal and external variables in the abundance of these
      two pre-recruitment stages. Our results indicate that, during their first five
      months of life, cod, haddock, and herring experience higher density-dependent
      survival than capelin. The abundance of age-0 cod depends on the mean age and
      biomass of the spawning stock, a result which has implications for the management
      of the entire cod stock. Temperature is another important factor influencing the
      abundance at age-0 and age-1 of all four species, except herring at age-1.
      Between age-0 and age-1, there is an attenuation of density-dependent survival
      for cod and herring, while haddock and capelin experience density dependence at
      high and low temperatures, respectively. Predation by subadult cod is important
      for both capelin and cod at age-1. We found strong indications for interactions
      among the studied species, pointing to the importance of viewing the problem of
      species recruitment variability as a community, rather than as a population
      phenomenon.

PMID- 17503592
TI  - Spatial anatomy of species survival: effects of predation and climate-driven
      environmental variability.
AB  - The majority of survival analyses focus on temporal scales. Consequently, there
      is a limited understanding of how species survival varies over space and,
      ultimately, how spatial variability in the environment affects the temporal
      dynamics of species abundance. Using data from the Barents Sea, we study the
      spatiotemporal variability of the juvenile Atlantic cod (Gadus morhua) survival.
      We develop an index of spatial survival based on changes of juvenile cod
      distribution through their first winter of life (from age-0 to age-1) and study
      its variability in relation to biotic and abiotic factors. Over the 25 years
      analyzed (1980-2004), we found that, once the effect of passive drift due to
      dominant currents is accounted for, the area where age-0 cod survival was lowest
      coincided with the area of highest abundance of older cod. Within this critical
      region, the survival of age-0 cod was negatively affected by its own abundance,
      by that of older cod, and by bottom depth. Furthermore, during cold years, age-0
      cod survival increased in the eastern and coldest portion of the examined area,
      which was typically avoided by older conspecifics. Based on these results we
      propose that within the examined area top-down mechanisms and predation-driven
      density dependence can strongly affect the spatial pattern of age-0 cod survival.
      Climate-related variables can also influence the spatial survival of age-0 cod by
      affecting their distribution and that of their predators. Results from these and
      similar studies, focusing on the spatial variability of survival rates, can be
      used to characterize species habitat quality of marine renewable resources.

PMID- 17503593
TI  - Local disturbance cycles and the maintenance of heterogeneity across scales in
      marine metapopulations.
AB  - In marine systems, the occurrence and implications of disturbance-recovery cycles
      have been revealed at the landscape level, but only in demographically open or
      closed systems where landscape-level dynamics are assumed to have no feedback
      effect on regional dynamics. We present a mussel metapopulation model to
      elucidate the role of landscape-level disturbance cycles for regional response of
      mussel populations to onshore productivity and larval transport. Landscape
      dynamics are generated through spatially explicit rules, and each landscape is
      connected to its neighbor through unidirectional larval dispersal. The role of
      landscape disturbance cycles in the regional system behavior is elucidated (1) in
      demographically open vs. demographically coupled systems, in relation to (2)
      onshore reproductive output and (3) the temporal scale of landscape disturbance
      dynamics. By controlling for spatial structure at the landscape and
      metapopulation levels, we first demonstrate the interaction between landscape and
      oceanographic connectivity. The temporal scale of disturbance cycles, as
      controlled by mussel colonization rate, plays a critical role in the regional
      behavior of the system. Indeed, fast disturbance cycles are responsible for
      regional synchrony in relation to onshore reproductive output. Slow disturbance
      cycles, however, lead to increased robustness to changes in productivity and to
      demographic coupling. These testable predictions indicate that the occurrence and
      temporal scale of local disturbance-recovery dynamics can drive large-scale
      variability in demographically open systems, and the response of metapopulations
      to changes in nearshore productivity.

PMID- 17503594
TI  - Composite forces shape population dynamics of copepod crustaceans.
AB  - Understanding the processes that control species abundance and distribution is a
      major challenge in ecology, yet for a large number of potentially important
      organisms, we know little about the biotic and abiotic factors that influence
      population size. One group of aquatic organisms that defies traditional
      demographic analyses is the Crustacea, particularly those with complex life
      cycles. We used likelihood techniques and information theoretics to evaluate a
      suite of models representing alternative hypotheses on factors controlling the
      abundance of two copepod crustaceans in a small, tropical floodplain lake.
      Quantitative zooplankton samples were collected at three stations in a Venezuelan
      floodplain lake from June through December 1984; the average sampling interval
      was two days. We constructed a series of models with stage structure that
      incorporated six biotic and abiotic covariates in various combinations to account
      for temporal changes in abundance of these target species and in their population
      growth rates. Our analysis produced several novel insights into copepod
      population dynamics. We found that multiple forces affected the abundance of
      particular stages, that these factors differed between species as well as among
      stages within each species, and that biotic processes had the largest effects on
      copepod population dynamics. Density dependence had a large effect on the
      survival of Oithona amazonica copepodites and on population growth rate of
      Diaptomus negrensis.

PMID- 17503595
TI  - Response of complex food webs to realistic extinction sequences.
AB  - Although an ecosystem's response to biodiversity loss depends on the order in
      which species are lost, the extinction sequences generally used to explore such
      responses in food webs have been ecologically unrealistic. We investigate how
      several extinction orders affect the minimum number of secondary extinctions
      expected within pelagic food webs from 34 temperate freshwater lakes. An
      ecologically plausible extinction order is derived from the geographically nested
      pattern of species composition among the lakes and is corroborated by species' pH
      tolerances. Simulations suggest that lake communities are remarkably robust to
      this realistic extinction order and highly sensitive to the reverse sequence of
      species loss. This sensitivity is not well explained by the known sensitivity of
      networks to the loss of highly connected species but appears to be better
      explained by our observation that trophic specialists preferentially consume
      widely distributed species at low risk of extinction. Our results highlight an
      important aspect of community organization that may help to maintain biodiversity
      amidst changing environments.

PMID- 17503596
TI  - Analysis of two-state multivariate phenotypic change in ecological studies.
AB  - Analyses of two-state phenotypic change are common in ecological research. Some
      examples include phenotypic changes due to phenotypic plasticity between two
      environments, changes due to predator/non-predator character shifts, character
      displacement via competitive interactions, and patterns of sexual dimorphism.
      However, methods for analyzing phenotypic change for multivariate data have not
      been rigorously developed. Here we outline a method for testing vectors of
      phenotypic change in terms of two important attributes: the magnitude of change
      (vector length) and the direction of change described by trait covariation
      (angular difference between vectors). We describe a permutation procedure for
      testing these attributes, which allows non-targeted sources of variation to be
      held constant. We provide examples that illustrate the importance of considering
      vector attributes of phenotypic change in biological studies, and we demonstrate
      how greater inference can be made than by evaluating variance components with
      MANOVA alone. Finally, we consider how our method may be extended to more complex
      data.

PMID- 17503597
TI  - How flexible is phenotypic plasticity? Developmental windows for trait induction
      and reversal.
AB  - Inducible defenses allow prey to modulate their phenotypic responses to the level
      of predation risk in the environment and reduce the cost of constitutive
      defenses. Inherent in this statement is that prey must alter their phenotypes
      during development in order to form these defenses. This has lead many ecologists
      and evolutionary biologists to call for studies that examine developmental
      plasticity to provide insights into the importance of development in controlling
      the trajectories of trait formation, the integration of phenotypes over ontogeny,
      and the establishment of developmental windows for trait formation and reversal.
      By moving away from studies that focus on a single point in development, we can
      obtain a more complete understanding of the phenotypic decisions and limitations
      of prey. We exposed freshwater snails (Helisoma trivolvis) to environments in
      which predatory water bugs (Belostoma flumineum) were always absent, always
      present, or added and removed at different points in development. We discovered
      that snails formed morphological defenses against water bugs. Importantly, after
      the initial induction of defenses, snails showed similar developmental
      trajectories as snails reared without predators. Further, the snails possessed
      wide developmental windows for inducible defenses that extended past sexual
      maturity. However, being induced later in development appeared to have an
      associated cost (i.e., decreased shell thickness) that was not found when water
      bugs were always present. This epiphenotype (i.e., new shell formation as an
      extension of the current shell) suggests that resource limitation plays an
      important role in responses to temporal variation in predation risk and may have
      critical ecological costs that limit the benefits of the inducible defense.
      Lastly, the ability of snails to completely reverse their defenses was limited to
      early in ontogeny due to the constraints associated with modular growth of shell
      material. In sum, we demonstrate that taking a developmental perspective is
      extremely valuable for understanding the ecology of inducible defenses.

PMID- 17503598
TI  - Ecological and evolutionary mechanisms for low seed: ovule ratios: need for a
      pluralistic approach?
AB  - Central to the ecology and evolution of a broad range of plants is understanding
      why they routinely have submaximal reproduction manifested as low seed : ovule
      and fruit : flower ratios. We know much less about the processes responsible for
      low seed : ovule ratios than we do for fruit : flower ratios. Current hypotheses
      for low seed : ovule ratios are largely drawn from those for fruit : flower
      ratios, including proximate (ecological) causes of pollen limitation, resource
      limitation, and pollen quality, as well as the ultimate (evolutionary) hypothesis
      of "bet hedging" on stochastic pollination. Yet, such mechanisms operating on
      fruit : flower ratios at the whole-plant level may not best explain low seed :
      ovule ratios at the individual-flower level. We tested each of these proximate
      and ultimate causes for low seed : ovule ratios using the specialized pollination
      mutualism between senita cacti (Pachycereus schottii) and senita moths (Upiga
      virescens). Seed : ovule ratios were consistently low (approximately 0.61). Such
      excess ovule production by senita likely has a strong genetic component given the
      significant differences among plants in ovule number and the consistency in ovule
      production by plants within and among flowering seasons. Excess ovule production
      and low seed : ovule ratios could not be explained by pollen limitation, resource
      limitation, pollen quality, or bet hedging. Nevertheless, phenotypic selection
      analyses did show significant selection gradients for increased ovule number,
      suggesting that other evolutionary processes may be responsible for excess ovule
      production and low seed : ovule ratios. In contrast, low fruit : flower ratios at
      the whole-plant level were explained by an apparent equilibrium between pollen
      and resource limitation. Thus, mechanisms responsible for low fruit : flower
      ratios at the whole-plant level are not necessarily in accord with those of low
      seed : ovule ratios at the individual-flower level. This suggests that we may
      need to adopt a more pluralistic approach to seed : ovule ratios and consider
      alternative hypotheses, including a greater array of proximate and ultimate
      causes. Initial results of this study suggest that floral allometry, selection on
      correlated floral traits, stigma clogging with pollen grains, and style clogging
      with pollen tubes may provide promising avenues for understanding low seed :
      ovule ratios.

PMID- 17503599
TI  - Spatial distribution of defense chemicals and markers and the maintenance of
      chemical variation.
AB  - Exploring the spatial distribution of variation in plant secondary metabolites is
      critical for understanding the evolutionary ecology of biochemical diversity in
      wild organisms. In the present study, concentrations of foliar sideroxylonal, an
      important and highly heritable defense chemical of Eucalyptus melliodora,
      displayed strong, fine-scale spatial autocorrelation. The spatial patterns
      observed could promote associational effects on herbivore foraging decisions,
      which may influence the selection pressures exerted on sideroxylonal content.
      Multiple chemical traits have roles in certain eucalypt-herbivore interactions,
      and the spatial characteristics of the herbivore foraging environment are
      therefore determined by these different factors. We used a model of E. melliodora
      intake by common brushtail possums (Trichosurus vulpecula), based on the combined
      effects of two chemical traits, to explore this idea and found that the spatial
      patterns were different to those of sideroxylonal alone. Spatial genetic
      autocorrelation, examined using microsatellites, was strong and occurred at a
      fine scale, implying that restricted gene flow might allow genetic patches to
      respond to selection relatively independently. Local two-dimensional genetic
      autocorrelation, explored using a new heuristic method, was highly congruent with
      the pattern of local phenotypic variation observed for sideroxylonal, suggesting
      that the genetic variance underlying the sideroxylonal variation is similarly
      structured. Our results suggest that the spatial distribution of genetic and
      phenotypic variation could influence both the selective pressure imposed by
      herbivores on eucalypt defenses and the potential of populations to respond to
      natural selection. Spatial context should be considered in future studies of
      plant-herbivore interactions.

PMID- 17503600
TI  - Genetics, environment, and their interaction determine efficacy of chemical
      defense in trembling aspen.
AB  - Optimal defense theories suggest that a trade-off between defense costs and
      benefits maintains genetic variation within plant populations. This study
      assessed the independent and interactive effects of genetic- and environment
      based variation in aspen leaf chemistry on insect performance, preference, and
      defoliation. Gypsy moth larvae were released into screenhouses containing eight
      aspen genotypes growing with high and low levels of nutrient availability. Plant
      chemistry, defoliation, and larval growth rates varied in response to genotype,
      nutrient availability, and their interaction. Total phenolic glycoside
      concentrations were inversely correlated with patterns of larval preference and
      were the best predictor of larval performance and defoliation among genotypes.
      Low-nutrient trees were less heavily defoliated and afforded decreased larval
      growth rates compared with high-nutrient trees. Nutrient availability mediated
      the defense benefits of phenolic glycosides, as plant chemistry explained
      significantly less variation in defoliation in low- compared with high-nutrient
      trees (7% vs. 44% of variation explained). These results suggest that spatial and
      temporal variation in resource availability may influence the relative magnitude
      of defense benefits in plants. Environmental mediation of the defense costs and
      benefits likely leads to diversifying selection and may maintain genetic
      polymorphisms in chemical defense traits in plant populations.

PMID- 17503601
TI  - Compensatory responses to loss of warming-sensitive plant species.
AB  - Climate warming-induced plant species loss is likely to be nonrandom and based on
      species-specific susceptibility to changing climate. We examined the ecological
      consequences of losing shallow-rooted forbs, a group of species we predict to be
      adversely affected by climate change based on their response to experimental
      warming. After three years of experimental species removal, tap-rooted forbs and
      grasses were able to fully compensate for the loss of shallow-rooted forbs with
      increased biomass production. Moreover, the remaining plant community yielded a
      larger biomass response to nitrogen addition when shallow-rooted forbs were
      removed, possibly because removal led to increased soil moisture. We conclude
      that, although shallow-rooted forbs share a common response to warming, their
      loss did not affect community-level biomass. However, the loss of shallow-rooted
      forbs could result in increased sensitivity to perturbations, such as changing
      nutrient availability. Our results demonstrate that realistic, nonrandom
      scenarios of species loss do not necessarily follow the general pattern of
      decreased productivity and dampened response to nitrogen addition with species
      loss that is predicted by theory and many experimental results. Further
      examinations of nonrandom species loss in other ecosystems are needed to further
      improve our understanding of the consequences of human-driven species loss.

PMID- 17503602
TI  - Slope aspect modifies community responses to clear-cutting in boreal forests.
AB  - Slope aspect modifies microclimate and influences ecological processes and
      spatial distribution of species across forest landscapes, but the impact of slope
      aspect on community responses to disturbance is poorly understood. Such insight
      is necessary to understand landscape community dynamics and resilience. We
      compared bryophyte (liverworts and mosses) communities in matched 0.02-ha plots
      of four boreal stand types in central Sweden: recently clear-felled and mature
      stands dominated by Norway spruce in south-facing and north-facing slopes.
      Differences between forests and clear-cuts were interpreted as effects of clear
      cutting, and differences between south- and north-facing slopes as effects of
      aspect. In response to clear-cutting, bryophyte cover and composition changed
      more in south-facing slopes. Only one out of ten significantly declining species
      in south-facing slopes also declined significantly in north-facing slopes. North
      facing slopes lost fewer bryophyte species, and among those, fewer forest species
      and fewer species associated with wood and bark. In north-facing slopes, the
      average proportions of mosses and liverworts shared between the forest and the
      clear-cut plot were 88% and 74%, respectively. Corresponding numbers for south
      facing slopes were 79% and 33%. In addition, more bryophyte species were added in
      north- than south-facing slopes after clear-cutting, somewhat reducing the
      difference in compositional change between aspects. South- and north-facing
      mature forests differed in species composition, mostly due to higher richness of
      mosses in south-facing slopes. The smaller changes in bryophyte communities on
      north-facing slopes in response to clear-cutting have implications for ecosystem
      dynamics and management as high local survival may enhance landscape-level
      resilience.

PMID- 17503603
TI  - Effect of prior disturbances on the extent and severity of wildfire in Colorado
      subalpine forests.
AB  - Disturbances are important in creating spatial heterogeneity of vegetation
      patterns that in turn may affect the spread and severity of subsequent
      disturbances. Between 1997 and 2002 extensive areas of subalpine forests in
      northwestern Colorado were affected by a blowdown of trees, bark beetle
      outbreaks, and salvage logging. Some of these stands were also affected by severe
      fires in the late 19th century. During a severe drought in 2002, fires affected
      extensive areas of these subalpine forests. We evaluated and modeled the extent
      and severity of the 2002 fires in relation to these disturbances that occurred
      over the five years prior to the fires and in relation to late 19th century stand
      replacing fires. Occurrence of disturbances prior to 2002 was reconstructed using
      a combination of tree-ring methods, aerial photograph interpretation, field
      surveys, and geographic information systems (GIS). The extent and severity of the
      2002 fires were based on the normalized difference burn ratio (NDBR) derived from
      satellite imagery. GIS and classification trees were used to analyze the effects
      of prefire conditions on the 2002 fires. Previous disturbance history had a
      significant influence on the severity of the 2002 fires. Stands that were
      severely blown down (> 66% trees down) in 1997 burned more severely than other
      stands, and young (approximately 120 year old) postfire stands burned less
      severely than older stands. In contrast, prefire disturbances were poor
      predictors of fire extent, except that young (approximately 120 years old)
      postfire stands were less extensively burned than older stands. Salvage logging
      and bark beetle outbreaks that followed the 1997 blowdown (within the blowdown as
      well as in adjacent forest that was not blown down) did not appear to affect fire
      extent or severity. Conclusions regarding the influence of the beetle outbreaks
      on fire extent and severity are limited, however, by spatial and temporal
      limitations associated with aerial detection surveys of beetle activity. Thus,
      fire extent in these forests is largely independent of prefire disturbance
      history and vegetation conditions. In contrast, fire severity, even during
      extreme fire weather and in conjunction with a multiyear drought, is influenced
      by prefire stand conditions, including the history of previous disturbances.

PMID- 17503604
TI  - Contrasted dynamics of northern Labrador tree lines caused by climate change and
      migrational lag.
AB  - The northern Quebec-Labrador tree lines are the most climatically stressed tree
      ecosystems of eastern North America. In particular, white spruce (Picea glauca)
      tree line populations distributed between 56 degrees N and 58 degrees N and 61
      degrees W and 66 degrees W show contrasted responses to recent changes in climate
      according to their geographic position relative to the Labrador Sea. Along the
      coast, the northernmost latitudinal and altitudinal tree lines responded
      positively to warming over the last 50 years with invading spruce several tens of
      meters above the current tree line. In contrast, white spruce tree lines across
      the wind-exposed Labrador plateau are located much higher in altitude and have
      receded a few tens of meters beginning around AD 1740-1750 and have not yet
      recovered. Whereas no field evidence of recent fire and insect damage was found,
      all inland tree line stands were progressively damaged likely due to mechanical
      defoliation of wind-exposed trees. Massive tree death in the 19th century caused
      a reduction in the number of seed-bearing trees, and declining tree lines were
      not replenished by seedlings. Recent warming reported for northern latitudes has
      not been strong enough to change the regressive tree line trajectory in interior
      Labrador. However, white spruce expansion above coastal tree line in the
      northernmost forest site in Labrador is in line with current climatic trends. It
      is hypothesized that the species is still advancing toward its potential tree
      line higher in altitude due to delayed postglacial migration. The slow advance of
      white spruce in northernmost coastal Labrador is likely caused by the rugged
      topography of the Torngat-Kaumajet-Kiglapait mountains.

PMID- 17503605
TI  - Latitudinal clines in food distribution correlate with differential migration in
      the Western Sandpiper.
AB  - We report that a latitudinal cline in intertidal food distribution is associated
      with the nonbreeding distribution of the Western Sandpiper (Calidris mauri). This
      novel result is the first to demonstrate a clear relationship between patterns of
      differential nonbreeding distribution and food availability for any shorebird
      species. Within each age class and sex, longer-billed Western Sandpipers winter
      further south. Moreover, females, the longer-billed sex, tend to winter south of
      males. Thus, both inter- and intra-sexual clines in bill morphology result in an
      overall gradient of increasing bill length from north to south. Longer-billed
      birds are able to extract prey that are buried more deeply in the sediment;
      therefore, we predicted shifts in the vertical distribution of food resources to
      coincide with the clines in bill morphology across the nonbreeding range. We
      tested our prediction by measuring biofilm density and the vertical distribution
      of macrofaunal invertebrates at six nonbreeding sites. Although no latitudinal
      trend was observed for biofilm, the vertical distribution of invertebrates was
      consistent with our prediction and revealed that the greatest relative abundance
      of surface prey occurred at northern nonbreeding sites and declined with
      decreasing latitude. We discuss the potential implications of these findings in
      the context of competing evolutionary hypotheses of differential migration and
      bill dimorphism in shorebirds.

PMID- 17503606
TI  - Nonideal breeding habitat selection: a mismatch between preference and fitness.
AB  - The selection of breeding sites in heterogeneous habitats should ideally be based
      on cues closely reflecting habitat quality and thus predicting realized
      individual fitness. Using long-term population data and data on territory
      establishment of male Northern Wheatears (Oenanthe oenanthe), we examined whether
      territory characteristics linked to individual fitness (reproductive performance
      and survival) also were linked to territory preference. Breeding territories
      varied in their physical characteristics and their potential effects on
      reproductive performance, and this variation among territories was correlated
      from one year to the next. Of all measured territory characteristics (from the
      focal and the previous year) only territory field layer height predicted
      individual fitness, i.e., reproductive performance was higher in territories with
      permanently short rather than growing field layers. Territory preference,
      instead, was only linked to the size of territory aggregations, i.e., males
      settled earlier at territory sites sharing borders with several adjacent sites
      than at those with few or no adjacent sites. This mismatch between territory
      characteristics linked to fitness and those linked to territory preference was
      not explained by site fidelity or compensated for by the different fitness
      components measured. Because the results were not in agreement with an ecological
      trap scenario, where poor habitats are preferred over high-quality habitats, our
      results suggest a more general case of nonideal habitat selection. Whereas
      nonideal selection with respect to territory field layer height may be explained
      by its poor temporal predictability within the breeding season, the preference
      for territory aggregations is still open to alternative adaptive explanations.
      Our study suggests that nonideal habitat selection should be investigated by
      direct estimates of preferences (e.g., order of territory establishment) and
      their links to habitat characteristics and fitness components. Furthermore, we
      suggest that the probability of establishing a territory needs to be included as
      a factor influencing patterns of habitat selection.

PMID- 17503607
TI  - EEG reviewing/recording strategy.
AB  - Accurate interpretation of EEGs requires the ability to detect, identify, and
      correctly characterize waveforms. Both technologists and reviewers can easily be
      lulled into a false sense of complacency when using digital recording. They may
      believe that rapidly optimizing the appearance of the EEG while it is being
      recorded or initially reviewed is not that important because an unlimited number
      of adjustments can be made later. Unfortunately, subtle EEG abnormalities may be
      missed entirely during initial review if such abnormalities occur infrequently
      and are masked by muscle artifact, low display gain, EKG contamination, or poor
      montage selection. No further review may be deemed necessary under these
      circumstances. Detection errors can be minimized if reviewers know how to
      optimize the appearance of each page and make the necessary adjustments quickly
      during the initial review of the EEG. EEG technologists can reduce detection
      errors by using optimal recording techniques to highlight any irregularities they
      encounter. The display parameters that can be quickly modified during review and
      acquisition are montage selection, filtering, sensitivity, and the number of
      seconds of EEG displayed on each page. The effect of these instrumentation
      changes upon the appearance of the EEG is discussed and examples are provided.

PMID- 17503608
TI  - Psychogenic nonepileptic seizures.
AB  - Psychogenic nonepileptic seizures are involuntary episodes of sensation,
      movement, or behavior that may mimic epileptic seizures but do not result from
      abnormal cortical discharges. The electroneurodiagnostic evaluation for suspected
      psychogenic nonepileptic seizures presents a confounding and challenging task to
      the physician/ technologist team. Because the events may closely mimic true
      epileptic seizures, it is reported that as many as one quarter of patients
      presenting to epilepsy centers with intractable, medication-refractory seizures
      are found to have been misdiagnosed as having epilepsy (Alsaadi and Marquez
      2005). Treatment regimens that are appropriate for epileptic seizures are
      inappropriate and ineffectual in the treatment of psychogenic nonepileptic
      seizures. In the absence of coexisting epilepsy, inappropriate diagnosis and
      treatment exposes these patients to the adverse effects of antiepileptic drugs,
      socioeconomic hardships (patients may be unable to work or drive or have limited
      social activities), and adds to the burden on healthcare resources (Benbadis
      2001). Video electroencephalography has become the gold standard in the
      diagnostic work-up to differentiate between seizures of neurologic origin and the
      nonepileptic somatic movements, sensations, and behaviors that are manifested by
      psychosocial distress.

PMID- 17503609
TI  - Disorders of communication: why do they talk like that?
AB  - People with communication disorders are seen frequently by electroneurodiagnostic
      technologists. Etiology of the disorders ranges from neurogenic, to anatomic and
      structural abnormality, to psychogenic, to developmental, to cryptogenic. After a
      short description of normal speech and language, this overview summarizes the
      disorders of speech and language providing a brief description of possible
      etiologies and symptomatology.

PMID- 17503610
TI  - Central therapeutic effects of peripheral vagus nerve stimulation.
AB  - Despite the recent addition of more than ten new antiepileptic drugs on the
      market, epilepsy remains poorly controlled in almost 30% of patients. For this
      subgroup of patients with pharmacoresistant epilepsy, vagus nerve stimulation
      (VNS) has become a viable option. More recently, it has also shown promise in
      treatment-resistant depression. This article discusses VNS's history, current
      applications, and potential to treat chronic neurologic and psychiatric
      disorders.

PMID- 17503611
TI  - Waveform window.

PMID- 17503612
TI  - Finger habits: their effects and their treatments--part 2.

PMID- 17503613
TI  - The language of dentistry.
AB  - Technical language associated with the practice of dentistry is a combination of
      the preceding word parts. Dental technical language is the combination of word
      roots, prefixes and suffixes plus abbreviations and acronyms. Familiarity with
      dental word combinations is useful for proper health care communication and is
      the first step in beginning to build a dental vocabulary that easily uses the
      singular and plural and is pronounced and spelled correctly.

PMID- 17503614
TI  - Rolling out the findings of a major study.

PMID- 17503615
TI  - Respiratory health effects of air pollution gases: modification by education and
      income.
AB  - The authors' purpose was to determine whether community income and education
      modify the effect of gaseous air pollution on respiratory hospitalizations. The
      authors used daily time-series analyses to test the association between daily
      respiratory hospitalizations and daily concentrations of ozone, carbon monoxide,
      sulfur dioxide, and nitrogen dioxide in 10 large Canadian cities. They calculated
      the percentage increase in hospitalizations for an increase in each air pollutant
      that was equivalent in magnitude to its mean value. The effect of nitrogen
      dioxide was stronger with decreasing levels of household income (p = .023). For
      the combined pollutant effect, percentage increases in hospitalizations ranged
      from 7.0% (95% confidence interval = 2.5-11.5) to -0.7% (95% confidence interval
      = -4.7-3.3) from lowest to highest quartile of education (trend test p = .001).
      Living in communities in which the individuals have lower household education and
      income levels may increase the individuals' vulnerability to air pollution.

PMID- 17503616
TI  - Asbestos-related cancers in refinery workers in the Australian petroleum
      industry.
AB  - In this study of the incidence of asbestos-related cancer in the Australian
      petroleum industry, the authors traced a cohort of 16,543 petroleum industry
      workers for a total of 226,989 person-years. There were 18 cases of pleural
      mesothelioma; 12 occurred in refinery nonoffice workers, for whom the
      Standardized Incidence Ratio was 3.77 (95% confidence interval = 1.95-6.59). The
      incidence of lung cancer was significantly lower than that in the general male
      population. Lung cancer incidence was higher in maintenance workers than in
      nonmaintenance workers, but the excess was not statistically significant, as it
      was based on small numbers with wide confidence intervals. Lung cancer rates in
      refinery workers did not increase with duration of employment; however, they did
      tend to be higher in workers hired in earlier decades. Excess mesothelioma
      incidence in refinery workers is confirmed, but it is likely that there are few
      if any asbestos-related lung cancers.

PMID- 17503617
TI  - Blood concentrations of selected volatile organic compounds and neurobehavioral
      performance in a population-based sample.
AB  - The authors analyzed data from a national sample to examine the relationships
      between blood concentrations of selected volatile organic compounds (VOCs) and
      the assessment scores of neurobehavioral evaluation tests. They calculated
      summary statistics to describe blood concentrations of 30 VOCs. For instance, the
      95th percentiles were as follows: 1,1,1-trichloroethane, 0.799 microg/l; 1,4
      dichlorobenzene, 11.081 microg/l; benzene, 0.476 microg/l; and toluene, 0.281
      microg/l. For 1,4-dichlorobenzene, benzene, dibromochloromethane, and
      trichloroethene, a blood level higher than the 95th percentile was associated
      with a poorer neurobehavioral assessment score than was a blood level up to the
      95th percentile. The authors found a linear relationship between blood toluene
      concentration and the Serial Digit Learning Test score. The findings suggest that
      exposure to certain VOCs may result in poor neurobehavioral performance. The
      study was exploratory and precludes a conclusive statement, so further
      investigation is warranted.

PMID- 17503618
TI  - Pterygium among Latino migrant farmworkers in North Carolina.
AB  - The authors describe the prevalence and severity of pterygium among Latino
      migrant farmworkers in North Carolina and delineate its risk factors. They
      selected a sample of 304 farmworkers working in eastern North Carolina in 2005.
      Digital photographs were taken of each farmworker, including a facial view
      showing the eyes. Two physicians independently rated each farmworker for the
      presence and severity of pterygia, with an initial intercoder agreement of 91%.
      Sixty-eight (23.3%) participants had a pterygium in at least 1 eye; 28 (9.5%) had
      bilateral pterygia. Age was significantly associated with pterygia (odds ratio =
      1.07; 95% confidence interval = 1.03-1.11). Research on the causes of pterygium
      among farmworkers is needed. In the interim, improvements in farmworkers'
      preventive behaviors, such as wearing ultraviolet protective lenses and brimmed
      hats, are reasonable and inexpensive measures.

PMID- 17503619
TI  - Association and correlation of self-reported home environmental factors and
      health symptoms.
AB  - The authors used community-based participatory research to survey 238 residents
      in public housing. They developed 9 exposure and 2 health symptom indexes through
      exploratory factor analyses. The univariate analysis showed that most
      environmental risk factors were associated with the symptom indexes. The authors
      found a statistically significant intercorrelation between 29 of 36 risk factor
      pairs. Because of this, most of the univariate associations lost statistical
      significance in multivariate models. The authors found a normal distribution of
      risk factors across household; however, risk factors per apartment were
      associated with symptoms. Environmental risk factors accounted for 2% to 26% of
      the variation in symptoms. The analysis suggests that correlation between factors
      could affect surveys in which researchers assess a small number of housing risk
      factors or assess larger numbers of factors without testing intercorrelation. The
      analysis is consistent with the possibility that building quality or housekeeping
      might drive the development of risk factors.

PMID- 17503621
TI  - Narrative styles, analytic styles.

PMID- 17503620
TI  - RE: "Effects of temperature and ozone on daily mortality during the August 2003
      heat wave in France" by Dear K, Ranmuthugala G, Kjellstrom T, Skinner C, Hanigan
      I, appearing in the July/August 2005 issue.

PMID- 17503622
TI  - Some forms of emotional disturbance and their relationship to schizophrenia.
      1942.

PMID- 17503623
TI  - Instinct and the ego during infancy. 1942.

PMID- 17503624
TI  - Work and motherhood: preliminary report of a psychoanalytic study.
AB  - This paper reports preliminary findings of a systematic inquiry into the manifest
      experience of conflict between paid work and motherhood. Psychoanalytic
      principles inform the design of a questionnaire and a research interview and the
      interpretation of data derived from both sources. An initial review of material
      from 140 questionnaires and 65 clinical interview series suggests that women vary
      tremendously in the ease or difficulty with which they navigate real obstacles to
      the integration of paid work and motherhood. The quality of a woman's
      relationship with her mother emerges as a singularly powerful influence on her
      experience of work-family balance.

PMID- 17503625
TI  - On the adolescent neurosis.
AB  - The author discusses the lifelong impact of adolescence in shaping the adult
      psyche. Some patients may appear to be as influenced by conflicts of adolescence
      and the individual solutions arrived at during this period as they are by
      conflicts and solutions of the oedipal phase, the author maintains. The subphases
      of early, middle, and late adolescence are discussed both in terms of a review of
      the psychoanalytic literature and of representative works of literary fiction.
      Illustrative clinical vignettes are presented as well.

PMID- 17503626
TI  - On thinking and not being able to think: reflections on viewing the Abu Ghraib
      photos.
AB  - Using experiences from childhood, from encounters with contemporary art, from
      clinical experience, and, most elaborately, from an initial viewing of the Abu
      Ghraib photos, the author argues that the interpretability of experience depends
      upon its being legible. This legibility, in turn, depends upon the interpreter
      maintaining contact with his/her own capacities for thought, and, more
      fundamentally, with the vitally necessary community of others with whom he/she
      shares those capacities.

PMID- 17503627
TI  - Wrestling with matter: origins of intersubjectivity.
AB  - Recent theories of intersubjectivity attach primacy to the creation of meaning
      between subjects, obscuring the role of the material world to which both Freud
      and Winnicott attached significance. Yet, as this article argues,
      intersubjectivity itself is predicated upon a transitional space between
      subjective creation and material life. After considering Winnicott's conceptions
      of psychesoma and transitionality, the author examines the developmental
      literature for precursors in the encounter with matter that set the stage for the
      emergence both of symbolic life and of an embodied "transitional subject" to come
      into being. Clinical illustrations are provided.

PMID- 17503628
TI  - Absence, ambiguity, and the representation of creativity in Vermeer's The Art of
      Painting.
AB  - This paper examines The Art of Painting, by Johannes Vermeer, to demonstrate how
      a great artist portrays the realm of imagination and creativity. The crucial
      points of entry for psychoanalysis reside in two sets of details in the painting
      that have generally been neglected by art historians: first, the contrast between
      the realistic rendering of certain parts of the work and the fuzzy, ambiguous
      nature of other elements; and second, the pervasiveness of the theme of absence
      in the manifest content. The author refers to some of Winnicott's and Lacan's
      concepts, particularly the connection between absence and desire as a spur to
      creativity.

PMID- 17503629
TI  - An optimistic turn.

PMID- 17503630
TI  - [Catheter ablation--an option for the treatment of chronic atrial fibrillation].

PMID- 17503631
TI  - [Is catheterisation the way to treat chronic atrial fibrillation?].

PMID- 17503632
TI  - [Acute humoral rejection after renal transplantion].

PMID- 17503633
TI  - [Effectiveness of anti-resorption therapy of postmenopausal osteoporosis].

PMID- 17503634
TI  - [Hashimoto's encephalopathy--a rare and unusual syndrome].

PMID- 17503635
TI  - [Hashimoto's encephalopathy--a rare and unsual syndrome].

PMID- 17503637
TI  - [Cognitive dysfunction in patients with systemic lupus erythemathosus with or
      without antiphospholipid antibodies].
AB  - INTRODUCTION: Impairment of cognitive functions is one of the neuropsychiatric
      symptoms of systemic lupus erythemathosus (SLE), the association of which with
      secondary antiphospholipid syndrome is often mentioned in the literature on the
      subject. Ethiology has not yet been fully clarified. PATIENTS AND METHODS: The
      aim of the study was to compare the "mini-mental state examination" (MMSE)
      outcomes in SLE patients with and without antiphospholipid antibodies (APA).
      RESULTS: Probands producing APA presented with significantly worse results in
      MMSE when compared to patients without these antibodies. There was no difference
      between patients with antisphospholipid syndrome and those with APA only.
      DISCUSSION AND CONCLUSION: Our study supports the notion that association of SLE
      with APA (not only with antiphospholipid syndrome) aggravates the deterioration
      of cognitive functions. MMSE test should not be omitted in the follow-up of SLE
      patients.

PMID- 17503636
TI  - [Catheter ablation of chronic atrial fibrillation using circumferential and
      complex linear lesions in the left atrium: modes of arrhythmia termination and
      long-term clinical outcome].
AB  - OBJECTIVE: The aim of the article is to present the method and results of
      catheter ablation for chronic atrial fibrillation. METHOD: Catheter ablation for
      chronic atrial fibrillation was performed in 82 patients (18 females, aged 54 +/-
      10 years), in 112 ablation procedures. Mean duration of the chronic phase of
      atrial fibrillation was 28 +/- 28 months. Before ablation, amiodarone was
      administered without effect to 74 (90%) patients, and was counter-indicated in 8
      (10%) patients. Ablation strategy consisted of circumferential lesions around the
      pulmonary veins and of complex linear lesions in the left atrium. Full pulmonary
      vein antra isolation, and sinus rhythm restoration, or at least converting atrial
      fibrillation into the left atrial tachycardia, were the procedure end points.
      RESULTS: Sinus rhythm was restored by ablation at least in one of the ablation
      procedures in 43 (52%) patients. During the follow-up period spanning 17.3 +/-
      11.6 months after the last ablation, stable sinus rhythm was achieved in 63 (77%)
      patients, of whom 38 (60%) had their sinus rhythm restored by ablation and
      another 14 (22%) their atrial fibrillation converted into the left atrial
      tachycardia. Of the 63 patients with stable sinus rhythm, class I or III
      antiarrhythmic medication has been maintained in 21 (33%) patients, and
      amiodarone has been taken by 13 (21%) patients. CONCLUSION: Catheter ablation of
      chronic atrial fibrillation is potentially highly effective in long-term
      restoration of sinus rhythm.

PMID- 17503638
TI  - [Acute humoral rejection of renal transplant].
AB  - Acute humoral rejection (AHR) is a rare complication which often results in the
      loss of kidney graft. The objective of this retrospective monocentric study was
      to evaluate two different approaches to AHR. Documentation of 730 patients was
      analysed, who underwent renal transplantation between 2002 and 2005. From 2002 to
      2003, patients with AHR were treated with 5 plasmaphereses (PF group, n = 13),
      and from 2004 to 2005 with a combination of 5 PF and intravenous immunoglobulins
      (PF + IVIG, 0.5 g/kg, n = 8). Data for the period of one year post-transplant was
      analysed. AHR occurred in 21 out of 730 patients (2.9%). Survival of grafts in
      the 6th month and in the 1st year was significantly higher for the PF + IVIG
      group than for the PF group only (p < 0.05). Patient survival was similar in both
      groups. The incidence of infectious complications was similar in both groups.
      There was a higher incidence of acute cellular rejections in the PF group (46.2
      vs. 14.3%) in control rebiopsies (performed due to deteriorated graft function or
      in order to check the efficiency of the treatment). It can be concluded that
      acute humoral rejection of transplanted kidney is a rare complication which can
      be treated by the combination of plasmaphereses and intravenous immunoglobulins.

PMID- 17503639
TI  - [Systemic and paraneoplastic manifestations of malignant diseases].
AB  - Timely diagnosis of malignant diseases largely depends on attention being given
      to early symptoms and on timely start of an extensive diagnostic process. Only
      this way can a tumour be diagnosed in its initial stage, and better effect of
      therapy can be achieved. The following overview provides a list of systemic
      (paraneoplastic - distant) manifestations of a tumour, and of symptoms related to
      local tumour expansion. The objective of the overview is to draw attention to all
      early symptoms of malignant diseases in patients, and to contribute to timely
      diagnosis and treatment.

PMID- 17503640
TI  - [Infection and atherosclerosis].
AB  - Atherosclerosis is a chronic inflammation and the cause of most cardiovascular
      diseases. It is the main cause of death in the Western world today, even though
      growing incidence of atherosclerosis-related diseases has been recently observed
      in developing countries, too. In many patients with atherosclerosis, however,
      traditional risk factors for atherosclerosis are not identifiable. This has
      renewed the interest, in recent years, in the links between atherosclerosis and
      environmental exposures, including infectious agents. Infection was identified as
      as risk factor for atherosclerosis in the first half of the 20th century.
      Experimental and clinical studies have shown that infection can stimulate
      atherogenic processes and that there are significant interactions between
      infection and traditional risk factors. Yet there are questions concerning
      etiology, pathogenesis and appropriate interventions which remain unanswered. The
      following article provides an overview of the role of the infectious agents in
      atherosclerosis and discusses possible intervention strategies.

PMID- 17503641
TI  - [Effectiveness of anti-resorption therapies of postmenopausal osteoporosis].
AB  - The aim of this article is to justify a need for evaluation of the absolute risk
      of fractures, to compare efficacy of antiresorptive therapies as indicated by
      large clinical trials, and to review currently available methods to assess
      efficacy of therapies in individual patients. It is emphasized that adherence to
      therapies is influenced not only by the individual bone efficacy and safety of
      the drug but also by beneficial impacts of the treatment on tissues other than
      bone.

PMID- 17503642
TI  - [Hashimoto's encepahlopthy--a rare and unusual syndrome].
AB  - Hashimoto's encephalopathy (HE) is a brain disease associated with autoimmune
      thyroid disease. Over 100 articles have been published on the topic, especially
      in connection with hypothyroidism. In addition to an overview of the relevant
      literature, we also report a case of a female patient with a rare association of
      HE with thyreotoxicosis. The patient presented with varied clinical-neurological
      symptoms: she had convulsions, psychotic symptoms, altered consciousness
      Examinations (laboratory tests, CT, MRI, EEG, CSL exams) detected increased level
      of proteins in the liquor, episodes of rhythmic delta activity on EEG, increased
      antithyreoidal antibody titre (TOOab, TGAb, TRAb) in serum. After initial
      treatment with carbimazole and hydrocortizone, the patient's condition
      dramatically improved and she was disconnected from artificial lung ventilation,
      conscious and convulsion-free. During the following 30 days, the patient would
      get worse after attempts to withdraw glucocorticoids. In spite of
      thyreotoxicosis, we classified the condition as HE and the patient was fully
      stabilised after pulse treatment with methylprednisolone. Clinically, the patient
      was subject to further outpatient follow up, without symptoms of encephalopathy;
      glucocorticoids were gradually withdrawn and were discontinued completely after
      another four months. The authors conclude that HE, even though rare, may pass
      unnoticed due to its symptoms which are similar to many other and more frequent
      diseases. HE should be considered in patients with potential or known autoimmune
      thyroidism and atypical neuropsychiatric manifestation responding to corticoid
      treatment.

PMID- 17503643
TI  - [Detection of ectopic gastric mucosa in Meckel's diverticulum by means of
      scintigraphy with 99mTc-pertechnetate in a 24-year old man].
AB  - AIM: The article presents a case of a 24-year old man with ectopic gastric mucosa
      in Meckel's diverticulum. Ectopic gastric mucosa may be present in Meckel's
      diverticulum and may be associated with peptic ulcer disease and lower
      gastrointestinal (GI) bleeding. Diagnosing ectopic gastric mucosa can largely
      benefit from 99"Tc-pertechnetate scintigraphy. MATERIAL AND METHOD: A 24-year old
      man underwent Meckel's diverticulum scintigraphy for timely anamnesis of GI
      bleeding from uncertain source (enterorrhagia, haemorrhagic anaemia). Upper tract
      and large bowel endoscopy, enteroclysis, ultrasound, CT and radioactive labelled
      red blood cells scintigraphy resluts were negative. RESULTS: Ectopic gastric
      mucosa was detected by 99mTc-pertechnetate scintigraphy. The patient underwent
      surgery and part of the proximal ileum including Meckel's diverticulum with
      ectopic gastric mucosa detected by histology was resected. CONCLUSION: Meckel's
      diverticulum scintigraphy can help detect ectopic gastric mucosa and improve the
      disease management in a patient with gastrointestinal bleeding.

PMID- 17503644
TI  - [The medical school faculty clinic--its primary goals of higher education and
      research].

PMID- 17503645
TI  - Australia's notifiable diseases status, 2005: annual report of the National
      Notifiable Diseases Surveillance System.
AB  - In 2005, 60 diseases and conditions were nationally notifiable in Australia.
      States and territories reported a total of 125,461 cases of communicable diseases
      to the National Notifiable Diseases Surveillance System: an increase of 10% on
      the number of notifications in 2004. In 2005, the most frequently notified
      diseases were sexually transmissible infections (51,557 notifications, 41% of
      total notifications), gastrointestinal diseases (29,422 notifications, 23%) and
      bloodborne diseases (19,278 notifications, 15%). There were 17,753 notifications
      of vaccine preventable diseases; 4,935 notifications of vectorborne diseases;
      1,826 notification of other bacterial infections (legionellosis, leprosy,
      meningococcal infections and tuberculosis) and 687 notifications of zoonotic
      diseases.

PMID- 17503646
TI  - Tuberculosis notifications in Australia, 2005.
AB  - The National Notifiable Disease Surveillance System received 1,072 tuberculosis
      (TB) notifications in 2005, of which 1,022 were new cases and 50 were relapses.
      The incidence of TB in Australia was 5.3 cases per 100,000 population in 2005 and
      has remained at a stable rate since 1985. The high-incidence groups remain people
      born overseas and Indigenous Australians at 20.6 and 5.9 cases per 100,000
      population, respectively. By contrast, the incidence of TB in the non-Indigenous
      Australian-born population was 0.8 cases per 100,000 population. Rates in the
      Australian-born, both Indigenous and non-Indigenous have been declining since
      1991, while rates in the overseas-born have been increasing. TB control in
      Australia relies on pre-migration screening and provision of free and effective
      treatment.

PMID- 17503647
TI  - Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance,
      2005.
AB  - The Australian Mycobacterium Reference Laboratory Network (AMRLN) collects and
      analyses laboratory data on new cases of disease caused by the Mycobacterium
      tuberculosis complex. In 2005, a total of 810 cases were identified by
      bacteriology; an annual reporting rate of 4.0 cases per 100,000 population.
      Isolates were identified as M. tuberculosis (n = 806), Mycobacterium africanum (n
      = 2) and Mycobacterium bovis (n = 2). Fifteen children aged under 10 years had
      bacteriologically-confirmed tuberculosis. Results of in vitro drug susceptibility
      testing were available for all 810 isolates for isoniazid (H), rifampicin (R),
      ethambutol (E), and pyrazinamide (Z). A total of 74 (9.1%) isolates of M.
      tuberculosis were resistant to at least one of these anti-tuberculosis agents.
      Resistance to at least H and R (defined as multi-drug resistance, MDR) was
      detected in 12 (1.5%) isolates; nine were from the respiratory tract (sputum n =
      8, bronchoscopy n = 1). Of the 74 M. tuberculosis isolates resistant to at least
      one of the standard drugs, 67 (90.5%) were from new cases, 6 from previously
      treated cases, and no information was available on the remaining case. Eight were
      Australian-born, 65 were overseas-born, and the country of birth of one was
      unknown. Of the 65 overseas-born persons with drug resistant disease, 41 (63.1%)
      were from 4 countries; Vietnam (n = 16), Papua New Guinea (n = 10), the
      Philippines (n = 9), and India (n = 6). A retrospective review of AMRLN data on
      isolates collected between 2000 and 2005 found that none of 70 MDR-TB isolates
      met the new definition for extensively drug resistant TB (XDR-TB, i.e. MDR-TB
      with additional resistance to quinolones and second-line injectable agents).

PMID- 17503648
TI  - Invasive pneumococcal disease in Australia, 2005.
AB  - Enhanced surveillance for invasive pneumococcal disease (IPD) was carried out in
      all Australian states and territories in 2005 with comparative data available
      since 2001. There were 1,680 cases of IPD notified to the National Notifiable
      Diseases Surveillance System in Australia in 2005; a notification rate of 8.3
      cases per 100,000 population. The rates varied between states and territories and
      by geographical region with the highest rates in the Northern Territory, the
      jurisdiction with the largest proportion of Indigenous people. Invasive
      pneumococcal disease was reported most frequently in those aged 85 years or over
      (41 cases per 100,000 population) and in 1-year-old children (36.5 cases per
      100,000 population). Enhanced data provided additional information on 1,015 (60%)
      of all notified cases. The overall rate of IPD in Indigenous Australians was 8.6
      times the rate in non-Indigenous Australians. There were 126 deaths attributed to
      IPD resulting in an overall case fatality rate of 7.5%. While the rate of IPD in
      the Indigenous under 2-year-old population decreased from 219 cases per 100,000
      population since targeted introduction of the 7-valent conjugate pneumococcal
      vaccine (7vPCV) in 2001, the rate in 2005 (94 cases per 100,000 population) was
      significantly greater than in non-Indigenous children (20.4 cases per 100,000
      population). Rates of disease in all children aged less than 2 years, caused by
      serotypes in the 7vPCV decreased by 75% between 2004 and 2005 as a result of the
      introduction of a universal childhood 7vPCV immunisation program. Significant
      decreases in IPD caused by 7vPCV serotypes also occurred in the 2-14 years and 65
      years or over age groups. There is no evidence of replacement disease with non
      vaccine serotypes. Serotypes were identified in 90% of all notified cases, with
      61% of disease caused by serotypes in the 7vPCV and 88% caused by serotypes in
      the 23-valent polysaccharide pneumococcal vaccine (23vPPV). Reduced penicillin
      susceptibility remains low and reduced susceptibility to 3rd generation
      cephalosporins is rare.

PMID- 17503649
TI  - Influenza surveillance in Victoria, 2006.
AB  - The Victorian influenza season in 2006 remained within normal seasonal activity
      thresholds and was relatively mild compared with recent years. The season peaked
      in mid-August, with influenza-like illness (ILI) rates from general practitioner
      sentinel surveillance and the Melbourne Medical Locum Service (MMLS), and cases
      of laboratory-confirmed influenza notified to the Department of Human Services,
      reaching their zeniths within one week of each other. A total of 74 general
      practitioners (GPs) participated in the sentinel surveillance in 2006, reporting
      a total of 136,732 consultations during the surveillance period from May to
      September inclusive. Participating GPs reported a total of 765 patients with an
      ILI; an average ILI rate of 5.6 cases per 1,000 consultations. The average ILI
      rate from the MMLS in the same period was 8.5 cases per 1,000 call-outs. Eighty
      two per cent of laboratory-confirmed influenza notifications during the
      surveillance period were type A; the remainder were type B. Typing indicated
      circulation of two predominant strains during the season:
      A/Wisconsin/67/2005(H3N2)-like virus and B/Malaysia/2506/2004-like virus. The
      influenza vaccine for 2006 contained A/New Caledonia/20/ 99(H1N1)-like virus,
      A/California/7/2004(H3N2)-like virus and B/Malaysia/2506/2004-like virus.

PMID- 17503650
TI  - Prevalence of antimicrobial resistances in common pathogenic Enterobacteriaceae
      in Australia, 2004: report from the Australian Group on Antimicrobial Resistance.
AB  - Antibiotic resistance in 3 common pathogenic types of Enterobacteriaceae was
      examined in a pointprevalence study in 2004. Strains of Escherichia coli,
      Klebsiello and Enterobacter species were collected prospectively in 25
      institutions in Australian capital cities and tested by broth microdilution to 12
      13-lactams and 3 other antibiotics. Almost 22% of isolates tested were from blood
      cultures. In E. coli, acquired resistance to ampicillin and piperacillin was
      common (> 40%), and clinically significant percentages of intermediate
      susceptibility and resistance (> 8%) were observed to amoxycillin-clavulanate,
      cefazolin and trimethoprim. In Klebsiella species, clinically important acquired
      resistance (> 8%) was seen to piperacillin, cephalothin and trimethoprim, while
      in Enterobacter species, this was found with piperacillin, ceftriaxone,
      ceftazidime and trimethoprim. Blood culture isolates had similar rates of
      resistance to isolates from other specimen sources. New South Wales/Australian
      Capital Territory (combined) tended to have higher percentages of resistance than
      the other states, which were otherwise comparable across the agents and species
      tested. Multi-resistance, defined as more than 3 acquired resistances to
      antibiotic classes, was found in 6.5% of E. coli, 8.3% in Klebsiella species and
      16.9% of Enterobacter species. Co-resistance to ciprofloxacin, gentamicin and/or
      trimethoprim was common in isolates presumptively harbouring extended-spectrum
      beta-lactamases. Strains with extended-spectrum beta-lactamases, although common
      in other countries, appear to be at fairly low levels in Australia; less than 4%
      in E. coli and less than 9% in Klebsiella species. Rates in Enterobacter species
      were not able to be determined. Presumptive plasmid-borne AmpC beta-lactamases
      were seen at low levels across the country and carbapenemases have now been found
      for the first time in Australia in Enterobacteriaceae. Both of these types of
      resistance represent a significant threat to major last-line antibiotics.

PMID- 17503651
TI  - Public health management of increased incidence of meningococcal disease in the
      Australian Capital Territory: 2003 to 2004.
AB  - This paper describes a sudden increase of meningococcal notifications in the
      Australian Capital Territory within a 3 month period, and the public health
      strategies used to manage it. There were 15 cases of meningococcal disease
      notified to the Communicable Disease Control (CDC) section, Australian Capital
      Territory Health (ACT Health), between 6 November 2003 and 5 February 2004. This
      was much higher than the annual average of 6 cases. The cases were notified in 2
      clusters. The first cluster of 8 cases, all serogroup C, was notified between 6
      November to 8 December 2003. Seven of these cases had an identical phenotype
      C:2a:P1.4 suggesting a common source. The second cluster of 7 cases was notified
      between 30 December 2003 and 5 February 2004. Of these, 5 were serogroup B, 1 was
      serogroup W-135 and 1 was serogroup C, whose phenotype (C:2a:P1.4) was identical
      to the phenotype of the first cluster of serogroup C cases. Phenotypes were not
      available for the serogroup B cases. There were 4 main interventions developed to
      manage the increased incidence based on the epidemiology of the cases; these were
      implemented concurrently. Factors that supported investigation and management
      were good surveillance systems, quick turnover of laboratory tests, regular
      communication with relevant health agencies and maintaining public awareness. As
      the number of cases notified was much higher than the annual average, the
      possibility of a community outbreak was considered. The Guidelines for the Early
      Clinical and Public Health Management of Meningococcal Disease in Australia
      (national guidelines) were consulted to determine whether there was an outbreak
      and the influence this had on management is also discussed.

PMID- 17503652
TI  - Large outbreaks of Salmonella Typhimurium phage type 135 infections associated
      with the consumption of products containing raw egg in Tasmania.
AB  - This report describes one of the largest egg-associated outbreaks of foodborne
      illness in Australia for many years. Between June and December 2005, five
      outbreaks of Salmonella Typhimurium phage type 135 were identified in Tasmania,
      leading to 125 laboratory-confirmed cases. Public health investigations included
      case and food handler interviews, cohort studies, environmental health
      investigations of food businesses, microbiological testing, traceback, and
      inspections and drag swabbing of an egg farm. These investigations enabled
      identification of foods containing raw egg or foods contaminated through
      inadequate food handling and/or storage procedures as possible vehicles for
      infection. A particular poultry farm was reported as the common source of eggs.
      Interventions targeting the general public and food handlers to promote better
      handling of egg products, and advice to egg producers regarding harm minimisation
      strategies led to the series of outbreaks being brought under control.

PMID- 17503653
TI  - Syphilis in remote north Queensland.

PMID- 17503654
TI  - OzFoodNet quarterly report, 1 October to 31 December 2006.

PMID- 17503655
TI  - Communicable diseases surveillance. Highlights for 4th quarter, 2006.
AB  - Communicable diseases surveillance highlights reports on data from various
      sources, including the National Notifiable Diseases Surveillance System (NNDSS)
      and several disease specific surveillance systems that provide regular reports to
      Communicable Diseases Intelligence. These national data collections are
      complemented by intelligence provided by state and territory communicable disease
      epidemiologists and/or data managers. This additional information has enabled the
      reporting of more informative highlights each quarter. The NNDSS is conducted
      under the auspices of the Communicable Diseases Network Australia. The NNDSS
      collates data on notifiable communicable diseases from state and territory health
      departments. The Virology and Serology Laboratory Reporting Scheme (LabVISE) is a
      sentinel surveillance scheme which collates information on laboratory diagnosis
      of communicable diseases. In this report, data from the NNDSS are referred to as
      'notifications' or 'cases' while data from the Lab VISE scheme are referred to as
      'laboratory reports'.

PMID- 17503656
TI  - Identifying safety concerns from genetic data: lessons from the development of
      CCR5 inhibitors.

PMID- 17503657
TI  - Insulin resistance, glucose intolerance and diabetes mellitus in HIV-infected
      patients.
AB  - An increased prevalence of insulin resistance, glucose intolerance and diabetes
      has been reported in HIV infection in the highly active antiretroviral therapy
      (HAART) era. This development might be clinically significant because of its
      association with cardiovascular morbidity and mortality as well as the
      therapeutic challenges of managing polypharmacy. The development of insulin
      resistance, glucose intolerance and diabetes could be related to the underlying
      HIV infection, the contribution of different antiretroviral agents, treatment
      associated weight gain, immune restoration, as well as the non-HIV related
      factors. Dissecting these factors in clinical practice might be difficult.
      Clinical studies include short-term treatments in healthy, non-HIV-infected
      individuals; randomized, controlled trials; comparative studies of different
      HAART regimens; and randomized studies of switching regimens in patients with
      viral suppression and stable immune function. This article reviews the latest
      knowledge regarding the epidemiology, pathogenesis, prevention and treatment of
      insulin resistance, glucose intolerance and diabetes mellitus in HIV-infected
      individuals.

PMID- 17503658
TI  - The V118I mutation as a marker of advanced HIV infection and disease progression.
AB  - BACKGROUND: The V118I mutation is included in the nucleoside analogue mutations
      (NAMs) set. It contributes to thymidine-analogue resistance and, consequently, to
      resistance to the whole nucleoside reverse transcriptase inhibitor (NRTI) class.
      We focused on the V1181 mutation in order to evaluate factors associated with its
      detection and its relationship with HIV progression. METHODS: Clinical and
      laboratory data at genotypic resistance test (GRT) of highly active
      antiretroviral therapy-failing patients were collected and their association with
      the V1181 mutation was analysed. Patients were also followed over time to
      determine factors related to progression to a new AIDS-related event or death.
      RESULTS: Of the 792 patients included, 114 (14.4%) carried the V118I mutation. In
      univariate analysis, the V118I mutation was significantly associated with a
      higher HIV RNA level, lower CD4+ T-cell count, Centers for Disease Control and
      Prevention (CDC) stage C, higher number of pre-GRT regimens and class-wide
      resistance (CWR) to NRTIs, protease inhibitors and nonnucleoside reverse
      transcriptase inhibitors. Higher numbers of pre-GRT regimens and NRTI CWR were
      also associated in the multivariable analysis. Within the post-GRT observation
      period of up to 6 years (median: 72 months; interquartile range: 33-109) 107
      events (58 new AIDS-related diseases and 49 deaths) were observed. Using the Cox
      proportional hazard model and the major clinical, behavioural and laboratory
      data, the V118I mutation was found to be associated with the endpoint (hazard
      ratio: 1.93, 95% confidence interval: 1.06-3.50; P=0.031). Other factors
      associated with disease progression were CDC stage C and lower CD4+ T-cell count
      at GRT. CONCLUSIONS: The analysis of our observational database suggests that the
      onset of the V118I mutation after treatment failure is unfavourable for the
      patient and can be considered a strong marker of disease progression.

PMID- 17503659
TI  - Improved prediction of response to antiretroviral combination therapy using the
      genetic barrier to drug resistance.
AB  - BACKGROUND: The outcome of antiretroviral combination therapy depends on many
      factors involving host, virus, and drugs. We investigate prediction of treatment
      response from the applied drug combination and the genetic constellation of the
      virus population at baseline. The virus's evolutionary potential for escaping
      from drug pressure is explored as an additional predictor. METHODS: We compare
      different encodings of the viral genotype and antiretroviral regimen including
      phenotypic and evolutionary information, namely predicted phenotypic drug
      resistance, activity of the regimen estimated from sequence space search, the
      genetic barrier to drug resistance, and the genetic progression score. These
      features were evaluated in the context of different statistical learning
      procedures applied to the binary classification task of predicting virological
      response. Classifier performance was evaluated using cross-validation and
      receiver operating characteristic curves on 6,337 observed treatment change
      episodes from the Stanford HIV Drug Resistance Database and a large US clinic
      based patient population. RESULTS: We find that the choice of appropriate
      features affects predictive performance more profoundly than the choice of the
      statistical learning method. Application of the genetic barrier to drug
      resistance, which combines phenotypic and evolutionary information, outperformed
      the genetic progression score, which uses exclusively evolutionary knowledge. The
      benefit of phenotypic information in predicting virological response was
      confirmed by using predicted fold changes in drug susceptibility. Moreover,
      genetic barrier and predicted phenotypic drug resistance were found to be the
      best encodings across all datasets and statistical learning methods examined.
      AVAILABILITY: THEO (THErapy Optimizer), a prototypical implementation of the best
      performing approach, is freely available for research purposes at
      http://www.geno2pheno.org.

PMID- 17503661
TI  - Effect of transient antiretroviral treatment during acute HIV infection:
      comparison of the Quest trial results with CASCADE natural history study.
AB  - OBJECTIVE: The benefit of transient combination antiretroviral treatment (CART)
      during acute HIV infection is uncertain. We used the seroconverter database
      CASCADE to provide a historical comparison for the Quest trial, in which 79
      subjects with acute HIV infection received CART for an average of 2.6 years, and
      17.7% (95% confidence interval [CI]: 10.9-27.6) fulfilled the primary endpoint of
      VL < or =1,000 copies/ml 24 weeks after CART discontinuation. METHODS: We
      estimated the prevalence of VL < or =1,000 copies/ml three years after
      seroconversion and prior to any ART among 385 sexually infected subjects in
      CASCADE who seroconverted between 1988 and 1996. We conducted a pre-specified
      comparison with the recently published Quest results, and considered potential
      biases. RESULTS AND DISCUSSION: The prevalence of VL < or =1,000 copies/ml at
      year three in CASCADE was 10.1% (95% CI: 7.5-13.5) (absolute difference compared
      to 17.7% in Quest: 7.6%; 95% CI: -0.1-17.8; P=0.053). In CASCADE, VL < or =1,000
      copies/ml was less common among homosexual and heterosexual men compared with
      women (8.5%, 7.3% and 17.6% respectively) and in subjects with symptomatic
      infection compared with those without (6.2% and 12.6%, respectively). As Quest
      had a much greater proportion of symptomatic subjects than CASCADE, any true
      difference in VL might be underestimated. Therefore this comparison suggests that
      transient CART in acute infection might result in a modest increase in the
      probability of low VL subsequently. However, several factors mitigate this
      conclusion. First, this historical comparison might be subject to other
      unmeasured confounders. Second, a comparison of median VL at the same time point
      was not significant (4.02 copies/ml and 4.20 copies/ml in Quest and CASCADE,
      respectively; P=0.55). Finally, additional analysis suggested that the observed
      difference in low VL at year three would be consistent with an immediate effect
      of CART only - a delay of usual VL decline without additional benefit.
      CONCLUSIONS: A small but significant proportion of seroconverters have low VL
      without ART. Transient CART in acute infection might increase the probability of
      low VL after treatment discontinuation, but such an effect is likely to be
      modest, and might represent a delay of natural history rather than a long-term
      therapeutic benefit.

PMID- 17503660
TI  - Altered heterochromatin organization after perinatal exposure to zidovudine.
AB  - BACKGROUND: Zidovudine (3'-azido-3'-deoxythymidine, AZT), administered to
      pregnant women alone or in combination with other antiretroviral drugs, greatly
      reduces the mother-to-child transmission of HIV-1. The potential genotoxicity of
      these molecules is underestimated and wide-ranging evaluation of its biological
      and clinical consequences is required. METHODS: We investigated the nuclear
      organization of constitutive heterochromatin, a major domain participating in
      epigenetic regulation, in uninfected infants born to HIV-1-infected mothers
      treated with zidovudine and/or other nucleoside reverse transcriptase inhibitors
      (NRTIs) during pregnancy. We studied the organization of chromosome 1
      heterochromatin (1q12) in peripheral leukocytes of 25 HIV-1-uninfected children
      (newborn to 9 years old): children born to HIV-1-infected mothers exposed to
      zidovudine and/or other NRTIs (n=15), children born to HIV-1-infected mothers not
      exposed to any NRTIs (n=6) and children born to HIV-1-uninfected mothers (n=4).
      RESULTS: Results differed significantly between NRTI-exposed and -unexposed
      children. By contrast, there was no difference between NRTI-unexposed children
      born to HIV-1-infected mothers and children born to HIV-uninfected mothers. The
      anomaly persisted in lymphocytes cultured for 48 h. There was no evidence of
      abnormal DNA methylation, a major feature of constitutive heterochromatin and
      associated with the loss of its structure. In a complementary sample of children,
      analysis of chromosome 11 and 16 heterochromatin suggests that the defect affects
      most of the other heterochromatic sites of the human genome. The heterochromatin
      defect persists long after the end of the exposure and appears in leukocytes of
      both myeloid and lymphoid lineages, suggesting that haematopoietic stem cells are
      affected.

PMID- 17503662
TI  - Liver triglyceride content in HIV-1-infected patients on combination
      antiretroviral therapy studied with 1H-MR spectroscopy.
AB  - OBJECTIVE: To carry out an exploratory evaluation of liver triglyceride content
      in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART)
      using proton magnetic resonance spectroscopy and to study how both the treatment
      itself and the biochemical and physiological variables in which the treatment
      causes alterations are related to liver fat content. METHODS: Intracellular
      hepatic triglyceride content was determined in 29 HIV-1-infected patients on
      their first HAART regime by means of localized water-unsuppressed single voxel
      proton spectra. Other measurements were body mass index, waist-to-hip ratio,
      lipodystrophy assessment and a detailed blood biochemical analysis. The
      relationship between intracellular hepatic triglycerides and relevant
      descriptive, treatment and biochemical variables was studied by correlation and
      regression analysis. RESULTS: Intrahepatic triglycerides were detected in 58.6%
      of the patients and 13.8% showed a triglyceride content compatible with liver
      steatosis. Many variables (body mass index, waist-to-hip ratio, cumulative
      exposure to PIs, lactate, insulin, insulin resistance measured by the homeostasis
      model assessment method [HOMA-R index], pH, total triglycerides, high density
      lipoprotein cholesterol and very low density lipoprotein [VLDL] cholesterol)
      correlated individually with the amount of triglycerides. Stepwise multiple
      regression analysis showed that the combination of insulin or HOMA-R index and
      VLDL cholesterol accounted for up to 50.2% of the triglyceride liver variance. A
      positive relationship was found between the concomitant presence of the metabolic
      syndrome components (insulin resistance, dyslipidaemia and central obesity) and
      intrahepatic triglyceride content. CONCLUSIONS: The study showed that
      intrahepatic triglyceride deposit appears to be a frequent feature of HIV-1
      infected patients receiving HAART. A coherent multifactorial combination of
      biochemical and physiological factors associated with the deposit suggested that
      cumulative exposure to PIs might be a possible trigger event.

PMID- 17503663
TI  - Relationship of mitochondrial DNA depletion and respiratory chain activity in
      preadipocytes treated with nucleoside reverse transcriptase inhibitors.
AB  - OBJECTIVE: To study the impact of adipocyte differentiation on nucleoside reverse
      transcriptase inhibitor (NRTI)-mediated mitochondrial DNA (mtDNA) depletion and
      to correlate mtDNA depletion with the activity of the respiratory chain
      complexes. METHODS: We studied adipocyte phenotype, viability, differentiation
      (CCAAT/enhancer-binding protein [C/EBP]-alpha and peroxisome proliferator
      activated receptor [PPAR]-gamma expression), adiponectin production, mtDNA
      content, activity of respiratory chain complexes and citrate synthase activity in
      3T3-L1 adipocytes. Cells were exposed to zidovudine (6 microM or 180 microM),
      stavudine (3 microM or 90 microM), and zalcitabine (0.1 microM or 3 microM) at
      different developmental stages for up to 2 months. RESULTS: Zidovudine and
      stavudine impaired adiponectin production in vitro at therapeutic Cmax
      concentrations, but none of the tested NRTIs had a negative impact on adipocyte
      differentiation or led to mtDNA depletion at these concentrations. Susceptibility
      of preadipocytes to mtDNA depletion was dependent on cell proliferation and
      differentiation, and mtDNA depletion occurred only after exposure to high drug
      concentrations. Under these conditions, stavudine led to up to 80% mtDNA
      depletion in both dividing and differentiating preadipocytes, whereas zidovudine
      affected mtDNA only in the differentiating cells. Despite mtDNA depletion by
      NRTIs, activity of the respiratory chain complexes was found to be unimpaired.
      CONCLUSIONS: We found mtDNA depletion in adipocytes but proliferation and/or
      differentiation of the cells seems to be a prerequisite for this phenomenon.
      Depletion of mtDNA up to 80%, however, was not associated with impaired
      respiratory chain activity in 3T3-L1 preadipocytes.

PMID- 17503664
TI  - New functional domains of human cytomegalovirus pUL89 predicted by sequence
      analysis and three-dimensional modelling of the catalytic site DEXDc.
AB  - INTRODUCTION: Benzimidazole D-ribonucleosides inhibit DNA packaging during human
      cytomegalovirus (HCMV) replication. Although they have been shown to target pUL56
      and pUL89, the large and small subunits of the HCMV terminase respectively, their
      mechanism of action is not yet fully understood. METHODS AND RESULTS: To better
      understand HCMV DNA maturation and the mechanism of action of benzimidazole
      derivatives, we studied the HCMV pUL89 protein by a genetic approach combined
      with primary structure analysis. The pUL89 sequence analysis of 25 HCMV strains
      and counterparts among herpesviruses allowed identification of 12 conserved
      regions. We also built a three-dimensional model of the pUL89 ATPasic catalytic
      site, including ATPase motor motifs 1, II and III, that may facilitate the
      development of future antiviral drugs active against HCMV. Finally, we identified
      several putative functional domains in pUL89, such as pUL89 zinc finger (pUL89
      ZF), DNA cutting sites and portal binding sites, that are probably involved in
      CMV DNA cleavage and packaging.

PMID- 17503665
TI  - Assessing theoretical risk and benefit suggested by genetic association studies
      of CCR5: experience in a drug development programme for maraviroc.
AB  - The proliferation of published gene association studies of the CCR5delta32
      mutation is of relevance to drug development of a CCR5 antagonist for HIV, in
      highlighting potential safety concerns. We conducted an initial review of all non
      HIV gene association studies of CCR5-delta32, followed by detailed meta-analyses
      in the three disease areas most commonly reported. Our review indicated no
      consistent evidence of increased risk of susceptibility to hepatitis C virus
      infection or multiple sclerosis among individuals with CCR5-delta32 mutation, and
      suggested treatment with a CCR5 inhibitor is unlikely to have related adverse
      effects. There was, however, evidence to suggest rheumatoid arthritis as a
      potential therapeutic target for a CCR5 antagonist. Clinical evidence would be
      required to confirm these findings.

PMID- 17503666
TI  - Clinical validation of saquinavir/ritonavir genotypic resistance score in
      protease-inhibitor-experienced patients.
AB  - OBJECTIVE: To identify a genotypic score for resistance to saquinavir boosted
      with ritonavir (SQV/r; 1,000/100 mg twice daily)-based regimens in protease
      inhibitor (PI)-experienced patients. METHODS: One-hundred and fifty-one PI
      experienced patients receiving a SOV/r-containing regimen were enrolled
      retrospectively. The virological response (VR) was defined as the decrease in HIV
      RNA at months 3-5. The effect of each mutation in the protease gene on the VR to
      SQV/r regimen was assessed using non-parametric univariate analyses and then a
      step-by-step analysis was carried out using a Jonckheere-Tepstra (JT)
      nonparametric test to retain the group of mutations most strongly associated with
      VR. RESULTS: Among the 138 patients with detectable plasma SQV, the median VR was
      -1.48 [range: -4 to +1.2] log10 copies/ml. Changes at 12 codons were associated
      with a reduced VR to SQV/r: codons 10, 15, 20, 24, 46, 54, 62, 71, 73, 82, 84 and
      90. The JT procedure led to selection of the following genotypic score, 10+15+20+
      24+62+73+82+84+90, as providing the strongest association with VR. In the 35
      patients with none of the mutations in this score, the median decrease in HIV RNA
      was -2.24 log10 copies/ml and it was -1.88 (n=29), -1.43 (n=24), -0.52 (n=30), 
      0.18 (n=9), -0.11 (n=6) and -0.30 (n=5) log10 copies/ml in those with 1, 2, 3, 4,
      5 and 6 mutations, respectively. CONCLUSION: With this resistance score to SQV/r,
      the isolates were classified as having no evidence of resistance (0-2), possible
      resistance (3) or resistance (> or =4) by grouping the number of mutations in
      samples for which the viral load reduction was similar.

PMID- 17503667
TI  - Nevirapine concentrations in HIV-infected children treated with divided fixed
      dose combination antiretroviral tablets in Malawi and Zambia.
AB  - OBJECTIVE: To investigate nevirapine concentrations in African HIV-infected
      children receiving divided Triomune tablets (stavudine+lamivudine+nevirapine).
      DESIGN: Cross-sectional study. METHODS: Steady-state plasma nevirapine
      concentrations were determined in Malawian and Zambian children aged 8 months to
      18 years receiving Triomune in routine outpatient settings. Predictors from
      height-for-age, body mass index (BMI)-for-age, age, sex, post-dose sampling time
      and dose/m2/day were investigated using centre-stratified regression with
      backwards elimination (P<0.1). RESULTS: Of the 71 Malawian and 56 Zambian
      children (median age 8.4 vs 8.5 years, height-for-age -3.15 vs -1.84,
      respectively), only 1 (3%) of those prescribed > or =300 mg/m2/day nevirapine had
      subtherapeutic concentrations (<3 mg/l) compared with 22 (23%) of those
      prescribed <300 mg/m2/day; most children with subtherapeutic nevirapine
      concentrations were taking half or quarter Triomune tablets. Lower nevirapine
      concentrations were independently associated with lower height-for-age
      (indicating stunting) (0.37 mg/l per unit higher [95% confidence interval (CI): 
      0.003, +0.74]; P=0.05), lower prescribed dose/m2 (+0.89 mg/l per 50 mg/m2 higher
      [95% CI: 0.32, 1.46]; P=0.002) and higher BMI-for-age (indicating lack of
      wasting) (-0.42 mg/l per unit higher [95% CI: -0.80, -0.04]; P=0.03).
      CONCLUSIONS: Currently available adult fixed-dose combination tablets are not
      well suited to children, particularly at younger ages: Triomune 30 is preferable
      to Triomune 40 because of the higher dose of nevirapine relative to stavudine.
      Further research is required to confirm that concentrations are reduced in
      stunted children but increased in wasted children. Development of appropriate
      paediatric fixed-dose combination tablets is essential if antiretroviral therapy
      is to be made widely available to children in resource-limited settings.

PMID- 17503668
TI  - Hypogonadism in HIV-1-infected men is common and does not resolve during
      antiretroviral therapy.
AB  - OBJECTIVES: To assess the prevalence of abnormal testosterone and gonadotropin
      values in HIV-infected men before and after 2 years of combination antiretroviral
      therapy (cART). DESIGN: Multicentre cohort of HIV-infected adults. METHODS: We
      identified 139 Caucasian antiretroviral-naive male patients who started
      zidovudine/ lamivudine-based cART that was virologically successful over a 2 year
      period. Ninety-seven were randomly chosen and plasma hormone determinations of
      free testosterone (fT) and luteinizing hormone (LH) at baseline and after 2 years
      of cART were evaluated. RESULTS: At baseline 68 patients (70%) had subnormal fT
      levels. In these, LH levels were low in 44%, normal in 47% and high in 9%. There
      was a trend for an association between lower CD4+ T-cell counts and hypogonadism.
      Most participants had normal FSH levels. No significant changes of fT, LH and FSH
      levels were observed after 2 years of cART. CONCLUSIONS: Low fT levels, mainly
      with normal or low LH levels and thus indicating secondary hypogonadism, are
      found in the majority of HIV-infected men and do not resolve during 2 years of
      successful cART.

PMID- 17503669
TI  - Molecular assessment of the potential for renal drug interactions between
      tenofovir and HIV protease inhibitors.
AB  - BACKGROUND: Active renal secretion of tenofovir (TFV) across proximal tubules
      occurs via uptake by human organic anion transporters 1 and 3 (hOAT1 and hOAT3)
      coupled with efflux by multidrug resistance protein 4 (MRP4). Co-administration
      of some HIV protease inhibitors (PIs) with tenofovir disoproxil fumarate (TDF),
      an oral prodrug of TFV, has been shown to increase systemic levels of TFV,
      leading to a hypothesis that PIs may affect tubular secretion of TFV and
      potentially alter the renal safety of TDF. METHODS: The effect of PIs on the
      transport of TFV by hOAT1, hOAT3 and MRP4 was assessed using in vitro cell-based
      transport models. RESULTS: At concentrations equal to their therapeutic peak
      plasma levels (Cmax) all PIs showed <20% inhibition of TFV transport by hOAT1.
      hOAT3 was more sensitive to Pls with ritonavir (RTV) and lopinavir being the most
      potent inhibitors of TFV transport (62% and 37% inhibition, respectively, at
      their Cmax). In the absence of human serum, RTV at concentrations exceeding its
      therapeutic Cmax also exhibited a minor effect on the cellular efflux of TFV by
      MRP4 (<30% inhibition at 20 microM). However, no effects of PIs on hOAT1, hOAT3
      or MRP4 were detected in the presence of human serum with the exception of RTV
      that inhibited hOAT3 by approximately 35% at its Cmax. In addition, PIs did not
      affect the cytotoxicity of TFV or TDF in MRP4- or MRP2-overexpressing cells.
      CONCLUSION: These data indicate a low potential of PIs to interfere with the
      active tubular secretion of TFV and to alter the clinical renal safety profile of
      TDF.

PMID- 17503670
TI  - A phase I/IIa study with succinylated human serum albumin (Suc-HSA), a candidate
      HIV-1 fusion inhibitor.
AB  - BACKGROUND: Succinylated human serum albumin (Suc-HAS) is a negatively charged
      neo-glycoprotein that binds to the positively charged V3-loop of HIV-1 gp120,
      acting as HIV-1-fusion inhibitor in vitro (IC50: 0.5-5.0 microg/ml). Suc-HSA was
      safe in rats and monkeys, and showed antiretroviral effect in a human-to-mouse
      model. We evaluated safety and pharmacokinetics of single and multiple doses of
      Suc-HSA in HIV-1-infected individuals. METHODS: First, six untreated, chronically
      HIV-1-infected patients were randomized to a single dose of 1 or 10 mg/kg Suc-HSA
      intravenously. Second, five consecutive daily doses (10 mg/kg, based on the
      results of the single dose study) were given to four patients. Safety laboratory
      assessments, Suc-HSA plasma levels, plasma HIV-1 RNA (pVL), and CD4+ T-cell
      counts were determined. RESULTS: Increase of liver transaminases (grade 1/2)
      occurred in one of six patients in the single-dose phase and in three of four
      patients in the multiple-dosing phase. Suc-HSA plasma levels were undetectable 4
      h after a single dose of 1 mg/kg. After a dose of 10 mg/kg, plasma levels were
      more sustained, but declined under the target plasma concentration (10 microg/ml)
      12-24 h post-dosing. After multiple dosing, plasma levels reached peak values 2h
      post-dosing as predicted by our kinetic model. However, trough levels were below
      the target concentrations. There was no change in pVL or CD4+ T-cell count in
      either the single- or multiple-dosing phase. CONCLUSIONS: At the chosen dosing
      regimens, adequate antiviral plasma levels were not maintained, probably because
      the hepatic clearance was more rapid than expected. This may partially explain
      the lack of effect on pVL and CD4+ T-cell count. The observed liver transaminase
      increases prohibit further dose escalation.

PMID- 17503671
TI  - Reversibility of cirrhosis in HIV/HBV coinfection.
AB  - HIV infection worsens the course and the natural history of chronic hepatitis B
      (HBV) leading to rapid progression to cirrhosis and to end-stage liver disease.
      Highly active antiretroviral therapy (HAART) regimens including nucleoside and/or
      nucleotide analogues with activity against both HIV reverse transcriptase and
      hepatitis B virus polymerase have clearly improved the survival rates of HIV/HBV
      coinfected patients. How HAART beneficially affects the natural course of chronic
      hepatitis B in coinfected patients is not known. We report a biopsy-proven case
      of reversal of HBV-related cirrhosis in a coinfected patient, paralleling long
      term suppression of HBV replication with tenofovir disoproxil fumarate as part of
      a HAART. Pathological reversibility of cirrhosis was ascertained by normalization
      of biochemical (platelet count) and morphological (abdominal ultrasonography and
      gastrointestinal endoscopy) tests as well as non-invasive markers of fibrosis. In
      conclusion, a HAART regimen including tenofovir disoproxil fumarate in a HBV/HIV
      coinfected cirrhotic patient might lead to sustained HBV viral suppression and
      result in cirrhosis reversal.

PMID- 17503672
TI  - The basic word on grievances.

PMID- 17503673
TI  - The new human papilloma vaccine.

PMID- 17503674
TI  - The institution of marriage: terminable or interminable?
AB  - The institution of marriage has received renewed interest and even appreciation
      in the context of the controversy regarding same-sex marriage. Paradoxically,
      though, as marriage has become more valued, it has become, in the minds of some,
      just another life-style choice. This paper presents an overview of marriage and
      explores the complexities of the institution from historical, anthropological,
      legal, and sociological perspectives. Marriage has many practical implications,
      including psychological and physical benefits for men and for women, and
      particularly for children and adolescents, as well as direct benefits to society
      itself. It is incumbent on clinicians to be sensitive to the many dimensions of
      this extraordinary institution as it relates to their patients.

PMID- 17503675
TI  - The role of clinical inference in psychoanalytic case formulation.
AB  - This article examines the role of clinical inference in the construction of
      psychoanalytic case formulations. The principles of analogy, especially in the
      context of contiguity, the repetition and convergence of themes, the theoretical
      predilections of the observer, and the assumptions one makes about the operation
      of the mind are among the major factors that influence the nature of the clinical
      inferences generated by psychodynamically oriented clinicians. Several clinical
      examples are presented to highlight the operation of these factors and how they
      can lead to alternate theoretical formulations.

PMID- 17503676
TI  - Shame and guilt: self-reflexive affects from the perspective of relationship and
      reciprocity.
AB  - The understanding of shame and guilt proposed here draws upon the concept of
      reciprocity to extend approaches based on object relations and structural theory.
      Shame is understood as an interface affect manifested in the context of external
      interaction. It constitutes the relational structure of self-consciousness by the
      internalization of a reciprocal relationship between subject and object. By
      contrast, guilt is an affective manifestation caused by the differentiation of
      the subject from a fusion of self and the other. First, it precipitates a
      disruption between subject and object. Second, it is used to restore oneness by
      regression.

PMID- 17503677
TI  - The practice of cognitive-behavior therapy in Roozbeh Hospital: some cultural and
      clinical implications of psychological treatment in Iran.
AB  - Contemporary cognitive-behavior therapy underscores the importance of the culture
      specific variables in the treatment of psychological problems. The flexibility
      and strengths of cognitive-behavior therapy provide us with an excellent
      opportunity to build a cultural model of cognitive-behavior therapy based on the
      clinical, as well as theoretical, knowledge of the practitioners and researchers
      working in different cultural settings. As a first step, we need to share our
      experiences with the other colleagues working in different cultures.

PMID- 17503678
TI  - Self-harm in South Asian women: a literature review informed approach to
      assessment and formulation.
AB  - The rates of self-harm among South Asian women in the United Kingdom are much
      higher than among their White counterparts. However, the explanation for this is
      far from clear, and there is a need for more culturally informed assessments for
      this group. Using literature review we identified cultural factors associated
      with self-harm in South Asian women. These findings were used to guide the
      clinical assessment of an Asian woman who had self-harmed using a personal
      narrative approach. Three independent clinicians analysed the narrative and
      identified important themes that gave an insight into the problems associated
      with the incident, arriving at a cultural formulation. Our interview showed that
      specific cultural factors, such as level of acculturation, cultural conflicts,
      stigma and interpersonal relationships, were important factors associated with
      distress and resilience. Literature reviews can help in conducting culturally
      competent assessments and enable better interventions for this group of patients.
      The key cultural areas identified are discussed in detail.

PMID- 17503679
TI  - Expression and treatment of depression among Haitian immigrant women in the
      United States: clinical observations.
AB  - Existing research demonstrates that culture has a profound impact on the
      expression and manifestation of mental illness, especially on depressive
      disorders among ethnically diverse populations. Currently, little research has
      focused on the Haitian population, despite the growing number of Haitians living
      in the United States. This paper discusses clinical observations of the
      expression of depression among Haitian immigrant women living in the United
      States. Specifically, this paper examines three distinctive types of depression
      (pain in the body, relief through God, and fighting a winless battle), explains
      their symptoms, and provides case examples to illustrate the expression of each
      type of depression. Additionally, the paper describes treatment processes for
      each type of depression and makes recommendations to mental health providers with
      respect to each type of depression. The information provided in this paper
      highlights the importance of a more systematic and scientific investigation of
      depression among Haitian women, men, and youths in the United States.

PMID- 17503680
TI  - Mapping the 24-hour emergency department cycle to improve patient flow.
AB  - BACKGROUND: Intermountain Healthcare (Salt Lake City), in conjunction with
      emergency department (ED) staff at LDS Hospital, designed an integrated patient
      tracking system (PTS) and a specialized data repository (ED Data Mart) that was
      part of an overall enterprisewide data warehouse. After two years of internal
      beta testing the PTS and its associated data captures, an analysis of various ED
      operations by time of day was undertaken. METHODS: Real-time data, concurrent
      with individual ED patient encounters from July 1, 2004 through June 30, 2005
      were included in a retrospective analysis. RESULTS: A number of patterns were
      revealed that provide a starting point for understanding ED processes and flow.
      In particular, ED census, acuity, operations, and throughput vary with the time
      of day. For example, patients seen during low-census times, in the middle of the
      night, appear to have a higher acuity. Radiology and laboratory utilization were
      highly correlated with ED arrivals, and the higher the acuity, the greater the
      utilization. DISCUSSION: Although it is unclear whether or not these patterns
      will be applicable to other hospitals in and out of the cohort of tertiary care
      hospitals, ED cycle data can help all facilities anticipate the resources needed
      and the services required for efficient patient flow. For example, the fact that
      scheduling of most service departments falls off after 5:00 P.M., just when the
      ED is most in need of those services, illustrates a fundamental mismatch between
      service capacity and demand.

PMID- 17503681
TI  - Eliminating perioperative adverse events at Ascension Health.
AB  - BACKGROUND: For Ascension Health's Healthcare That Is Safe strategy, Sacred Heart
      Hospital (SHH) and Columbia St. Mary's (CSM) served as alpha sites to develop
      strategies to eliminate perioperative adverse events (POAEs). The alpha sites set
      an interim goal of a 50% reduction of POAEs, then 100%, or elimination of POAEs
      by July 2008. IMPLEMENTATION: The alpha sites identified a process for data
      management to establish clear, measurable elements for each of the five
      strategies of the alpha initiative; created an infrastructure to foster
      transformational change in the operating room suite; and implemented tactics to
      measure the success of the five strategies. STRATEGIES AND TACTICS: The sites
      implemented tactics for five strategies: (1) prevention of errors due to human
      factors, (2) prevention of surgical site infections, (3) prevention of adverse
      perioperative cardiac events, (4) prevention of postoperative venous
      thromboembolism, and (5) prevention of postoperative hemorrhage. RESULTS: Both
      alpha sites achieved > or = 90% reduction in the POAE rate. DISCUSSION: A number
      of key learnings were drawn from the alpha experiences, including the need to
      adjust to evolving definitions and guidelines for implementation and measurement
      of perioperative care.

PMID- 17503682
TI  - How do teams in quality improvement collaboratives interact?
AB  - BACKGROUND: The multi-organizational collaborative is a popular model for quality
      improvement (QI) initiatives. It assumes organizations will share information and
      social support. However, there is no comprehensive documentation of the extent to
      which teams do interact. Considering QI collaboratives as networks, interactions
      among reams were documented, and the associations between network roles and
      performance were examined. METHODS: A telephone survey of official team contact
      persons for 94 site teams in three QI collaborarives was conducted in 2002 and
      2003. Four performance measures were used to assess the usefulness of ties to
      other teams and being considered a leader by peers. RESULTS: Eighty percent of
      the teams said they would contact another team again if they felt the need. Teams
      made a change as a direct result of interaction in 86% of reported relationships.
      Teams typically exchanged tools such as software and interacted outside of
      planned activities. Having a large number of ties to other teams is strongly
      related to the number of mentions as a leader. Both of these variables are
      related to faculty-assessed performance, number of changes the ream made to
      improve care, and depth of those changes. DISCUSSION: The Findings suggest that
      collaborative teams do indeed exchange important information, and the social
      dynamics of the collaborarives contribute to individual and collaborative
      success.

PMID- 17503683
TI  - Clinical inertia: a common barrier to changing provider prescribing behavior.
AB  - BACKGROUND: A cross-sectional content analysis nested within a randomized,
      controlled trial was conducted to collect information on provider responses to
      computer alerts regarding guideline recommendations for patients with suboptimal
      hypertension care. METHODS: Participants were providers who cared for 1,017
      patients with uncontrolled hypertension on a single antihypertensive agent within
      Veterans Affairs primary care clinics. All reasons for action or inaction were
      sorted into a framework to explain the variation in guideline adaptation.
      RESULTS: The 184 negative provider responses to computer alerts contained
      explanations for not changing patient treatment; 76 responses to the alerts were
      positive, that is, the provider was going to make a change in antihypertensive
      regimen. The negative responses were categorized as: inertia of practice (66%),
      lack of agreement with specific guidelines (5%), patient-based factors (17%),
      environmental factors (10%), and lack of knowledge (2%). Most of the 135
      providers classified as inertia of practice indicated, "Continue current
      medications and I will discuss at the next visit." The median number of days
      until the next visit was 45 days (interquartile range, 29 to 78 days).
      DISCUSSION: Clinical inertia was the primary reason for failing to engage in
      otherwise indicated treatment change in a subgroup of patients. A framework was
      provided as a taxonomy for classification of provider barriers.

PMID- 17503684
TI  - Improving medication reconciliation in the outpatient setting.
AB  - BACKGROUND: A systematic study into outpatient medication reconciliation was
      conducted to determine if a multifaceted intervention influencing providers and
      patients reduced discrepancies related to inadequate prescription medication
      reconciliation in an outpatient setting. METHODS: A prospective trial was
      conducted on 104 primary care patients at the Mayo Clinic. Patients in Phase I
      received standard care. Patients in Phase II received the intervention
      reconciliation process, which consisted of (1) mailed letters before appointments
      to remind patients to bring medication bottles or updated medication lists to
      their visits, (2) verification, and (3) correction of the medication list in the
      electronic medical record by the patient, and academic detailing and weekly audit
      and feedback of performance. RESULTS: Interventions resulted in a decrease in
      prescription medication errors from 88.9% of the visits in Phase 1 to 66% of the
      visits in Phase II (p = .005) and from 98.2% of the visits in Phase I to 84% of
      the visits in Phase II (p = .0134) when all medications were considered. The
      average number of discrepancies per patient decreased by more than 50% from 5.24
      in Phase I to 2.46 in Phase II. The majority of discrepancies were minor.
      DISCUSSION: A multifaceted intervention including various members of the health
      care provider team (and the patient) is crucial to enhancing medication
      reconciliation.

PMID- 17503685
TI  - Errors prevented by and associated with bar-code medication administration
      systems.
AB  - As expected, bar-code medication administration systems can prevent medication
      errors. However, health care organizations must be aware of identified failure
      points in bar coding that may contribute to errors.

PMID- 17503686
TI  - Young adults' reactions to grandparent painful self-disclosure: the influence of
      grandparent sex and overall motivations for communication.
AB  - This study examined young adult grandchildren's self-reports about the influence
      of grandparent sex on perceived grandparent painful self-disclosure (PSD) as well
      as their reactions to grandparent dyad PSD. Perceived grandmother and grandfather
      motivations for overall communication were assessed as mediators of young adult
      grandchildren's discomfort with grandparent dyad PSD. Findings show that
      participants perceived PSD more in their interactions with their maternal
      grandmothers compared to their maternal grandfathers. These young adult
      grandchildren were less likely to report discomfort if they perceived
      grandparents to be communicating overall for the purposes of positive affect, or
      identity, but more likely to feel discomfort if they perceived grandparents to be
      communicating for the purpose of control.

PMID- 17503687
TI  - Emotional development across adulthood: differential age-related emotional
      reactivity and emotion regulation in a negative mood induction procedure.
AB  - The present study examines the hypothesis that older adults might differentially
      react to a negative versus neutral mood induction procedure than younger adults.
      The rationale for this expectation was derived from Socioemotional Selectivity
      Theory (SST), which postulates differential salience of emotional information and
      ability to regulate emotions across adulthood. The present data support a view of
      differential age-related effects of negative mood inductions with greater and
      more heterogeneous emotional reactivity among older adults, who showed a
      substantially greater decrease in self-rated pleasantness, calmness, and
      wakefulness than younger adults. Moreover, relative to the younger adults,
      emotion regulation in terms of mood repair was more effective among the older
      adults. The age-related mood effects are discussed in terms of SST and have
      practical implications for the study of emotion and cognition across adulthood.

PMID- 17503688
TI  - Factors affecting burden of South Koreans providing care to disabled older family
      members.
AB  - This study examined the determinants of caregiving burden among South Koreans who
      care for their disabled older family members. A sample of 1000 primary caregivers
      taken from the Comprehensive Study for Elderly Welfare Policy in Seoul, South
      Korea was analyzed. Independent variables included the demographic
      characteristics of caregivers and care recipients, the severity of cognitive
      impairment among care recipients, care recipients' functional abilities,
      financial adequacy and caregivers' degree of social support. Hierarchical
      regression was used to predict the levels of caregivers' burden. Similar to
      western care providers, South Korean caregivers who were in poor health and who
      had little informal social support, inadequate financial resources and more
      weekly caregiving hours were more likely to experience intense caregiving burden.
      Burden was also positively related to the functional and cognitive disabilities
      of care recipients. The results of this study indicate that certain aspects of
      caregiving are unique to South Koreans. Daughters-in-law were the most common
      caregiver within the sample which indicates that South Korean eldercare is non
      consanguineous. Identifying predictors of South Korean caregivers' burden
      promotes a more comprehensive understanding of cultural experiences in caring for
      older adults.

PMID- 17503689
TI  - Aspirations for older age in the 21st century: what is successful aging?
AB  - The literature on successful aging reveals a wide range of definitions, generally
      reflecting the academic discipline of the investigator. Biomedical models
      primarily emphasise physical and mental functioning as successful aging; socio
      psychological models emphasise social functioning, life satisfaction and
      psychological resources as successful aging. Several studies also identify these
      factors as the precursors of successful aging. Moreover, research shows that
      older people consider themselves to have aged successfully, but classifications
      based on traditional medical models do not. Fewer studies have explored lay
      views, and most of these have been exploratory or restricted to specific groups
      of areas. A model of successful aging needs to be multi-dimensional, incorporate
      a lay perspective for social significance, use a continuum rather than
      dichotomous cut-offs for "success" and lack of, and distinguish clearly between
      predictor and constituent variables.

PMID- 17503690
TI  - The influence of upcoming food-pellet delivery on subjects' responding for 1%
      sucrose reinforcement delivered by concurrent random-interval schedules.
AB  - Researchers have demonstrated that rats' rates of operant responding that are
      maintained by 1% liquid-sucrose reinforcement will increase if food-pellet
      reinforcement is upcoming within the same session. The authors investigated
      whether a similar induction effect would be observed when rats pressed a lever
      for 1% sucrose that was delivered by concurrent random-interval schedules of
      reinforcement. Results demonstrated that upcoming noncontingent food-pellet
      delivery increased absolute response rates on the concurrent schedules in 10 of
      12 possible instances. Upcoming food-pellet delivery also increased subjects'
      sensitivity to reinforcement on the concurrent schedules, as measured by the
      generalized matching law (W. M. Baum, 1974), in 5 of 6 possible instances. The
      present results extended the finding of induction to responding on concurrent
      schedules. They also added to evidence suggesting that the effect occurs because
      the reinforcing value of the weak reinforcer (i.e., the 1% sucrose) has been
      increased.

PMID- 17503691
TI  - The influence of intertrial interval food on extinction and devaluation in chain
      schedules.
AB  - The authors exposed pigeons to 2 equal 3-link chains by using variable-interval
      schedules of reinforcement. An intertrial interval (ITI) bisected by free food
      separated the chains. After baseline training, the authors presented terminal
      links in a successive discrimination to devalue 1 terminal link: The authors
      reinforced responses to 1 terminal link and extinguished responses to the other.
      The authors then presented full chains in extinction, except that they continued
      to deliver free food during the midpoint of the ITI. There were 2 principal
      findings. First, across all extinction conditions, responding decreased but did
      not extinguish. Second, when extinction testing revealed a terminal link
      devaluation effect in the 3rd condition, responding to the initial link was
      affected, but not middle-link responding. Overall, the results suggested that ITI
      food presentations can exert a substantial effect on responding in 3-link chain
      schedules, and they appear to influence both the pattern of extinction and
      devaluation effects.

PMID- 17503692
TI  - Brief flight to a familiar enclosure in response to a conditional stimulus in
      rats.
AB  - The authors observed brief, directed movement to a familiar enclosure in rats to
      determine whether this behavior is part of a rat's defensive repertoire when
      exposed to a conditional-fear stimulus. In Experiment 1, upon exposure to the
      compound conditional-fear stimulus of tone and light, only rats that received
      paired presentations of the conditional stimuli and shock fled into a small,
      familiar enclosure where they then froze. Rats that had received unpaired
      presentations did not enter the enclosure in significant amounts when later
      tested. In Experiment 2, the authors observed rats' freezing and use of either a
      familiar or an unfamiliar enclosure when tested with a conditional-fear stimulus.
      Rats tested with a familiar enclosure entered it more quickly than did rats
      without prior exposure to the enclosure. Freezing was greatest when both training
      and testing environments were similar with respect to access to the enclosure.
      The results of these 2 experiments support the idea that brief, directed flight
      in rats is a component of the postencounter stage of predatory imminence (M. S.
      Fanselow & L. S. Lester, 1988) and is compatible with freezing.

PMID- 17503693
TI  - The effects of cross-fostering on inherent sensorimotor gating deficits exhibited
      by Brattleboro rats.
AB  - Prepulse inhibition (PPI) of the startle reflex is an operational measure of
      sensorimotor gating, a process critical to normal cognitive function. Researchers
      (D. Feifel & K. Priebe, 2001) have identified PPI deficits in the Brattleboro
      rat, a genetically vasopressin-deficient strain that is derived from the Long
      Evans rat. The absence of vasopressin, a neuropeptide involved in affiliative
      behaviors, may adversely affect the rearing of offspring by Brattleboro dams,
      perhaps accounting for their attenuated PPI. Cross-fostering of Long Evans and
      Brattleboro pups did not alter the PPI deficits in Brattleboro rats. However, the
      magnitude and habituation of the startle response, which normally differs between
      Brattleboro and Long Evans rats, was not different in cross-fostered rats. The
      authors' results indicated that abnormal rearing by Brattleboro dams may
      contribute to the startle magnitude and habituation abnormalities in Brattleboro
      Rats but not to their PPI deficits, suggesting that their sensorimotor gating
      deficits result from their genetic deviation from Long Evans rats.

PMID- 17503694
TI  - Ordinal-list integration for symbolic, arbitrary, and analog stimuli by rhesus
      macaques (Macaca mulatta).
AB  - Two numeral-trained monkeys learned to produce 3 5-item lists of Arabic numerals,
      colors, and arbitrary signs in the correct sequence. The monkeys then responded
      at above-chance levels when the authors tested them with nonrewarded pair-wise
      comparisons of items from different lists, indicating their use of ordinal
      position information. The authors also tested the monkeys with nonrewarded pair
      wise comparisons of an analog quantity and an item from 1 of the 3 learned lists.
      Although the monkeys were not trained to serially order analog quantities, 1
      monkey correctly integrated the analog quantities with the lists of numerals,
      colors, and signs. The consistent use of an ordinal rule, despite different types
      of training and varying degrees of experience with the 4 types of stimuli,
      suggested that the monkey had a robust concept of ordinality.

PMID- 17503695
TI  - Delay of gratification and delay maintenance by rhesus macaques (Macaca mulatta).
AB  - The authors tested the self-control of rhesus macaques by assessing if they could
      refrain from reaching into a food container to maximize the accumulation of
      sequentially delivered food items (a delay-maintenance task). Three different
      versions of the task varied the quantity and quality of available food items. In
      the first 2 versions, food items accumulated across the length of the trial until
      a monkey consumed the items. In the 3rd task, a single less-preferred food item
      preceded a single more-preferred food item. Some monkeys delayed gratification
      even with relatively long delays between deliveries of items. However, the data
      suggested that self-control, in the majority of tested individuals, was not
      significantly different across different task versions and that self-control by
      macaques was not as prevalent in these tasks as it is in chimpanzees and human
      children.

PMID- 17503696
TI  - A Stroop-like effect in color-naming of color-word lexigrams by a chimpanzee (Pan
      troglodyte).
AB  - The Stroop effect (J. R. Stroop, 1935) reflects the difficulty in ignoring
      irrelevant, but automatically processed, semantic information that is inherent in
      certain stimuli. With humans, researchers have found this effect when they asked
      participants to name the color of the letters that make up a word that is
      incongruent with that color. The authors tested a chimpanzee that had learned to
      associate geometric symbols called lexigrams with specific colors. When the
      chimpanzee had to make different responses that depended on the color of stimuli
      presented to her, she showed a Stroop-like effect when researchers presented to
      her the previously learned symbols for colors in incongruent font colors. Her
      accuracy performance was significantly poorer with these stimuli than with
      congruent color-referent lexigrams, noncolor-referent lexigrams, and nonlexigram
      stimuli, although there were not any significant differences in response latency.
      The authors' results demonstrated color-word interference in a Stroop task with a
      nonhuman animal.

PMID- 17503697
TI  - Behavioral consistency in a changed social context in Carolina chickadees.
AB  - Stable personality-like influences on behavior have been documented in nonhuman
      animals (S. D. Gosling, 2001), but little is known about such influences within
      explicitly social contexts. The authors tested whether individuals of a socially
      complex avian species, Carolina chickadees (Poecile carolinensis), show
      consistent behavioral profiles when their social context changes. Consistency was
      tested using 7 groups of chickadees, each group comprising 2 female-male pairs.
      The 2 pairs from each group were isolated from one another until the male birds
      were switched between the pairs. The authors made several measures before and
      after the male switch, including measures of affiliative and agonistic behavior,
      self-maintenance behavior, and vocalizations. The authors observed strong
      behavioral consistency despite the major change in social context, suggesting
      that personality can influence this fundamental social relationship.

PMID- 17503698
TI  - Deliberate practice in dogs: a canine model of expertise.
AB  - The acquisition of expertise is an area of controversy between those who lean
      more toward learning and those who lean more toward talent. Because the genetics
      and early life experiences of humans are not open to direct manipulation, human
      studies are of limited use in this debate. Studies using nonhumans as expert
      models may prove useful in resolving this dispute. For nonhumans to be considered
      proper models of human experts, there must be evidence supporting a shared
      acquisition mechanism. A candidate mechanism is deliberate practice. The author
      tested the deliberate practice theory of expertise acquisition on dogs competing
      in the sport of agility. The author examined the relationships between amounts of
      accumulated deliberate practice and agility performance measures. The author
      found there was a statistically significant relationship between the amount of
      deliberate practice and measured performance in agility dogs, even when
      controlling for sex, breed group, age, and height.

PMID- 17503699
TI  - Tree thinking: a new paradigm for integrating comparative data in psychology.
AB  - Over the past 15 years, several important theoretical and methodological
      developments have emerged from evolutionary biology. These developments-
      collectively dubbed tree thinking--are now well known in evolutionary biology but
      have yet to be incorporated into mainstream psychology. Tree thinking has
      revolutionized evolutionary biology and has the potential to do the same for how
      comparative data are integrated into psychology. Tree thinking holds that
      explanations (or narratives) for adaptations must be based on an understanding of
      the adaptations' history (or chronicle) over evolutionary time. This tenet of
      tree thinking requires researchers to consider hitherto neglected patterns of
      data. The authors present the ideas and methods behind tree thinking, examining
      their implications for psychology.

PMID- 17503700
TI  - Pattullo Lecture 2006. Crossing the educational chasm: preparing healthcare
      leaders for interprofessional practice.
AB  - Despite marked differences in training and professional interests, physicians and
      hospital administrators face similar problems: failure of reimbursement to keep
      pace with rising costs, new therapeutic modalities, critical workforce shortages,
      increasing government and managed care regulation, heightened consumerism, & an
      aging patient population. In the face of these mounting challenges, both
      physicians and hospital administrators could benefit significantly from a climate
      of collaboration and interdependence to optimize interprofessional practice.
      Teaching people to work with other healthcare professionals who play key roles in
      healthcare delivery is an important educational mission for the Association of
      University Programs in Health Administration (AUPHA) and for society in general.

PMID- 17503701
TI  - Memories of Walter J. McNerney: his contributions to health administration and to
      health administration education.

PMID- 17503702
TI  - Evidence-based healthcare management competency evaluation: alumni perceptions.
AB  - An ongoing concern of healthcare educators is how well students are prepared for
      practice after they are graduated. Curriculum design and pedagogical methods are
      central components for developing healthcare management and leadership
      competencies. Various stakeholders have identified competency domains and
      typologies that outline the requisite skills and expertise to manage and lead
      healthcare organizations. This study analyzes survey data over a ten-year period
      from alumni one-year post graduation to compare self-reported assessment of
      competency development. Trends across two graduate professional programs tailored
      to different students of healthcare administration are compared. A total of 302
      alumni responded to the survey. A factor analysis is performed to evaluate how
      the skills, knowledge, and abilities of graduates fit into identified competency
      domains. Fourteen competencies on the survey load into four factor domains:
      leadership, communication, business skills, and technology.

PMID- 17503703
TI  - Cultivating next generation leadership: preceptors' rating of competencies in
      post-graduate administrative residents and fellows.
AB  - Substantial national attention is being directed at enhancing the competency
      levels of early careerists in healthcare management. In this study, we examined
      preceptors' ratings of administrative resident/fellow competencies in multiple
      domains, and we compared those to our previous results of self-rated competency
      by residents/fellows. In this national sample of preceptors (n=61) of
      administrative residency/fellowship program listed with the American College of
      Healthcare Executives, competency in the information management domain was ranked
      highest, with more than half of preceptors (55.7%) giving their residents/fellows
      an "A" rating. Fewer preceptors (between 30.0% and 39.2%) gave their
      residents/fellows an "A" rating in domains of interpersonal and emotional
      intelligence, analytic and conceptual reasoning, and clinical operations. Less
      than 20% of preceptors rated competencies as "A" level in the domains of human
      resources/marketing/public affairs, financial management, fund raising, and
      facilities management. There were significant differences in preceptor ratings
      compared with resident/fellow self-ratings, with preceptors often providing lower
      ratings than provided by resident/fellows. The findings highlight the need not
      only to enhance competency levels of graduates but also to address the potential
      mismatch in early careerists' and preceptors' views about required and attained
      competency levels.

PMID- 17503704
TI  - Bridging the gap: academic and practitioner perspectives to identify early career
      competencies needed in healthcare management.
AB  - Healthcare organizations, health management professional associations, and
      educational institutions have begun to examine carefully what it means to be a
      fully competent healthcare executive. As a result, an upsurge in interest in
      healthcare management competencies has been observed recently. The present study
      uses two critically important groups of informants as participants: health
      management practitioners and faculty. Using the nominal group process, health
      administrators identified critical environmental issues perceived to have an
      impact on healthcare executives today. These issues were employed in a card-sort
      assessment and a survey was administered to a nationwide sample of health
      administrators. These data were used to create a map and five clusters of the
      environmental landscape of healthcare management. These clusters of environmental
      issues provided a framework for having groups of administrators and faculty
      members generate and rank perceived behavioral competencies relative to each
      cluster. Implications for healthcare management practice, education, and research
      are discussed.

PMID- 17503705
TI  - My to do list.

PMID- 17503706
TI  - The time has come. Describing and shaping RN practice.

PMID- 17503707
TI  - Perioperative nursing: a class of their own.

PMID- 17503708
TI  - Food guides reflect similarities and differences in dietary guidance in three
      countries (Japan, Canada, and the United States).
AB  - Food guides to help consumers make healthy choices have recently been released in
      three countries: Japan, Canada, and the United States. The visual symbol that
      introduces key concepts is a spinning top in Japan, a rainbow in Canada, and a
      pyramid in the United States. The main features of the new guides are given in
      printed consumer resources, and more detailed information is available at related
      websites. Although the process of developing the guides varied among the
      countries, the resulting recommended food patterns are remarkably consistent.

PMID- 17503709
TI  - A new food guide in Japan: the Japanese food guide Spinning Top.
AB  - The Dietary Guidelines for Japanese, released in 2000, provides the basics of a
      healthy diet for the people of Japan. In July 2005, the Ministry of Health,
      Labour and Welfare and the Ministry of Agriculture, Forestry and Fisheries of
      Japan jointly released a new pictorial guide, The Japanese Food Guide Spinning
      Top, to help people implement the Dietary Guidelines for Japanese. It guides
      people as to what kinds and how much food they should eat each day to promote
      health. This paper describes the nature of the diet and the theoretical framework
      applied in the development of the new guidelines.

PMID- 17503710
TI  - Eating well with Canada's Food Guide (2007): development of the food intake
      pattern.
AB  - A food intake pattern specifying amounts and types of food was created for
      Canada's revised food guide, Eating Well with Canada's Food Guide (2007), using a
      two-step modeling process. In step one, food composites were manipulated to
      develop a food intake pattern. The second step used the step one food intake
      pattern to create 500 simulated diets for each of 16 age and gender groups. The
      resulting nutrient content distributions were evaluated relative to Dietary
      Reference Intake reference values. The modeling cycled between these two steps
      until a satisfactory pattern was achieved. The final pattern reflects modeling, a
      review of associations between foods and chronic disease, and input received
      during consultation.

PMID- 17503711
TI  - Lowered concentrations of branched-chain amino acids result in impaired growth
      and neurological problems: insights from a branched-chain alpha-keto acid
      dehydrogenase complex kinase-deficient mouse model.
AB  - Excess circulating levels of branched-chain amino acids (BCAA), as seen in maple
      syrup urine disease, result in severe neuropathology. A new mouse model,
      deficient in the kinase that controls BCAA catabolism, shows that very low
      circulating levels of BCAA are also associated with neuropathology, including the
      development of epileptic seizures. These mice clearly demonstrate the need to
      control essential amino acid levels within both upper and lower limits.

PMID- 17503712
TI  - Coffee consumption and risk of type 2 diabetes and heart disease.
AB  - Coffee seems to have distinct acute and long-term effects on health, which can be
      modified by genetic background. Coffee consumption is potentially protective
      against the development of type 2 diabetes, but given the lack of a solid
      biological basis for this association, and the possible adverse cardiovascular
      effects of coffee, recommendations for optimal coffee intake are difficult to
      establish.

PMID- 17503713
TI  - [Sexology and medicine].

PMID- 17503714
TI  - [Androgen deficiency in women: indication and risks of testosterone or DHEA
      treatment].
AB  - Androgen deficiency syndrome is defined by impaired well being and libido in
      women with adequate estrogenization and low levels of total serum testosterone
      (T). The causes of low T levels are discussed. Seven placebo controlled studies
      have shown that percutaneous administration of T is able to increase sexual
      activity and libido in ovariectomized women (5 studies), after hypophysectomy and
      in natural menopause. DHEA (50 mg/d) is beneficial only in women with Addison
      disease or after hypophysectomy but not in natural adrenopause. Other beneficial
      and side effects of androgenotherapy are discussed in particular the breast
      cancer risk.

PMID- 17503715
TI  - [Benign prostate hypertrophy and sexual health].
AB  - This article is centered on the possible impact of benign prostate hypertrophy on
      the male sexual life. Not only concerning the symptomatology of this affection
      but also concerning the side-effects of medication as well as, if necessary, a
      surgical intervention. A particular attention is given to the possibility of
      using new associations between medication, for instance between alpha-blockers
      and inhibitors of 5-phosphodiesterases.

PMID- 17503716
TI  - [Male sexual function after stroke].
AB  - Stroke represents the third leading cause of death, ranking behind heart disease
      and cancer and it is the major cause of worldwide long-term disability after the
      age of 65. Stroke has an important psychological and emotional impact on the
      patient and his environment. Some trials show the substantial lowering of libido,
      of the frequency of sexual intercourse, the presence of erectile dysfunction and
      reduced sexual satisfaction. After stroke it is important to evaluate the
      relational and sexual aspects of the patient and his sexual partner. A
      specialized consultation should be proposed when necessary to optimise the
      patient's post-stroke rehabilitation.

PMID- 17503717
TI  - [Interactions between human sexual arousal and sexual desire: a challenge for
      social neuroscience].
AB  - The frequent interaction and synergy between sexual arousal and sexual desire
      occuring during a sexual experience explains the difficulty in disentagling these
      two phenomena in the human sexual response. Sexual desire is defined as a goal
      directed motivational state integrating the other in one's personal sphere on the
      basis of intentionality, rather than by instinct only. Sexual arousal includes
      physical manifestations and subjective perception of excitement. Interest in
      sexual arousal has engendered a growing body of research concerning its nature
      and function as well as the biological basis of the mechanisms sustaining it.
      Recent functional imaging has played a key role in seeking to isolate brain
      regions specific to sexual arousal. This field may represent a new challenge for
      social neuroscience.

PMID- 17503718
TI  - [Sexological problems in a psychaitric consultation].
AB  - In a psychiatric consultation, the discovery in patients of a coexistent sexual
      problem is not something unlikely. In spite of representing a complication or a
      serious co-morbidity, that discovery could be an opportunity in favour of the
      psychiatric treatment. It is nevertheless necessary for the psychiatrist to
      realise all the possible connections between the two kinds of pathology.

PMID- 17503719
TI  - [The devil's sperm is cold: about sexuality in the medical practice].
AB  - "The devil's sperm is cold!". Is the present medical attitude really more
      pertinent than this scolastic statement used by the Saint Inquisition to track
      down witches? The purpose of the present article is to question our modern
      attitude and to confront it to medical practice. Everyone will work out his one
      vision of sexuality in conformity with the time he lives in. If the field of
      sexuality were limited to sexology, then the physician would probably not offer a
      great help to his patients to reduce their sexual problems; thus it is worthwhile
      to accurately describe the various attitudes and questions involved. It is hoped
      that their outmatching would make it possible for the physician to create a new
      approach in the still significant framework of the doctor-patient relationship.

PMID- 17503720
TI  - [Fever and weight loss in a 57-year-old patient].
AB  - Presentation of a 57-year-old female patient with fever of unknown origin,
      asthenia, and weight loss for I month. History and examination were unremarkable.
      Blood analysis showed an important inflammatory syndrome. Other paraclinic tests
      were all normal. Finally, sophisticated exams (CT-scan, and FDG PET-scan) allowed
      the diagnosis of giant cell arteritis, confirmed by biopsy of the temporal
      arteries. Differential diagnosis and treatment are discussed.

PMID- 17503721
TI  - [Legal regulations towards generic medications].

PMID- 17503722
TI  - [A 5 year old boy with hair loss. Trichotillomania].

PMID- 17503723
TI  - [The plague, the alarm and antibiotics: re-reading of a press release].

PMID- 17503724
TI  - [Non heart beating organ donation: history and ethics (2)].

PMID- 17503725
TI  - [Euthanasia and physician-assisted suicide: confusion in France ].

PMID- 17503726
TI  - [One quarter of American soldiers serving in Iraq and in Afghanistan suffer from
      mental health disorders].

PMID- 17503727
TI  - [National dissonance and the health care crisis].

PMID- 17503729
TI  - [Endothelial dysfunction and vascular pathology].
AB  - Endothelium-dependent relaxations are due to the release by the endothelial cells
      of potent vasodilator substances. The best characterized endothelium-derived
      relaxing factor (EDRF) is nitric oxide (NO), from 1-arginine by the constitutive
      endothelial NO synthase. In arterial smooth muscle, NO stimulates soluble
      guanylate cyclase which leads to the accumulation of cyclic GMP. Endothelial
      cells also release substances (EDHF) that hyperpolarize vascular smooth muscle.
      The release of NO from the endothelium can be mediated by both Gi
      (catecholamines, serotonin, thrombin) and Gq (adenosine diphosphate, bradykinin)
      G-proteins. In arteries with regenerated endothelium and/or atherosclerosis,
      there is a selective loss of the Gi mechanism of No-release which favours the
      occurrence of vasospasm, thrombosis and cellular growth. In addition to relaxing
      factors, the endothelial cells can produce contracting-substances (EDCF) which
      include superoxide anions, endoperoxides, thromboxane A2 and endothelin-1. The
      propensity to release EDCFs is maintained or even augmented in diseased blood
      vessels. The switch from a normally predominant release of NO to that of EDCF may
      play a crucial role in vascular disease.

PMID- 17503728
TI  - Gene therapeutic prospects in early onset of severe retinal dystrophy:
      restoration of vision in RPE65 Briard dogs using an AAV serotype 4 vector that
      specifically targets the retinal pigmented epithelium.
AB  - Previous studies have tested gene replacement therapy in RPE65 deficient dogs
      using recombinant adeno-associated virus 2/2 (rAAV2/2), -2/1 or -2/5 mediated
      delivery of the RPE65 gene. They all documented restoration of dark- and light
      adapted ERG responses and improved psychophysical outcomes. Use of a specific
      RPE65 promoter and a rAAV vector that targets transgene expression specifically
      to the retinal pigmented epithelium (RPE) may, however, provide a safer setting
      for the long-term therapeutic expression of RPE65. Subretinal injection of rAAV2
      pseudotyped with serotype 4 (rAAV2/4) specifically targets the RPE. The purpose
      of our study was to evaluate a rAAV2/4 vector carrying a human RPE65cDNA driven
      by a human RPE65 promoter, for the ability to restore vision in RPE65-/- purebred
      Briard dogs. Recombinant rAAV2/4 and rAAV2/2 vectors containing similar human
      RPE65 promoter and cDNA cassettes were generated and administered subretinally in
      8 affected dogs, ages 8 to 30 months (n = 6 with rAAV2/4, n = 2 with rAAV2/2).
      Although fluorescein angiography and OCT examinations displayed retinal
      abnormalities in treated retinas, electrophysiological analysis demonstrated that
      restoration of rod and cone photoreceptor function started as soon as 15 days
      post-injection, reaching maximal function at 3 months post-injection, and
      remaining stable thereafter in all animals treated at 8 to 11 months of age. As
      assessed by the ability of these animals to avoid obstacles in both dim and
      normal light, functional vision was restored in the treated eye, while the
      untreated contralateral eye served as an internal control. The dog treated at a
      later age (30 months) did not recover retinal function or vision, suggesting that
      there might be a therapeutic window for the successful treatment of RPE65 -/-
      dogs by gene replacement therapy.

PMID- 17503730
TI  - [Albert Claude, an exceptional man].

PMID- 17503731
TI  - [Ethics questions in transplantations].

PMID- 17503732
TI  - Heparan sulfate mediates neuroprotection from degeneration in experimental
      glutaric aciduria.
AB  - Glutaric aciduria type 1 (GA1) is a childhood metabolic disorder associated with
      crises that lead to striatal necrosis. Although the disorder can be controlled
      with diet, there is no current treatment to ameliorate the neurodegeneration
      following a metabolic crisis. We hypothesized that heparan sulfate (HS)
      administration would stimulate neural stem cell proliferation by dimerizing with
      FGF-2 and binding to the FGF-2 receptor on neural stem cells, thus enhancing the
      number of newly generated neurons to repair damage following a metabolic crisis.
      In addition, FGF-2 is known to exert neuroprotective effects independent of
      neurogenesis, so HS may also have neuroprotective activities. To test these
      hypotheses, ibotenic acid was injected into the striatum of adult mice, mimicking
      the metabolic crisis and damage caused by glutaric aciduria. Daily doses of HS
      and bromodeoxyuridine (BrdU) or BrdU alone were administered starting 1 day after
      the ibotenic acid lesion. BrdU was used to label dividing cells. Fluorescent
      immunohistochemistry was used to quantify the lesion size and evaluate the
      phenotype of BrdU-positive cells. Intrastriatal administration of ibotenic acid
      resulted in a substantial striatal lesion that occupied 18.5% of the ipsilateral
      brain hemisphere. In contrast, animals treated with HS exhibited a lesion volume
      representing <1% of the ipsilateral brain hemisphere (ANOVA; p < 0.0001).
      Increased neurogenesis, however, was not observed in this group. These results
      suggest that HS administration 2 days after a "metabolic crisis" can ameliorate
      brain injury in an animal model of GA1. The neuroprotective mechanisms of HS,
      however, remain to be elucidated but may exert their actions indirectly through
      binding with FGF-2.

PMID- 17503733
TI  - Galantamine effects on memory, spatial cue utilization, and neurotrophic factors
      in aged female rats.
AB  - Galantamine is an acetylcholine esterase inhibitor that has been approved for use
      in Alzheimer's disease. However, even though clinical studies indicate efficacy
      in attenuating some of the symptoms associated with the disease, there are a
      paucity of studies evaluating the effects of galantamine administration on
      cognitive performance and brain parameters in aged rats. Further, because all
      previous animal studies using galantamine have been performed in male rats, there
      is no information on how females respond to galantamine treatment. Therefore, we
      studied the effects of 0.3, 0.6, and 1.2 mg/kg/day galantamine in 20-month-old
      female rats in terms of performance on the working and reference memory water
      radial arm maze task. Galantamine did not influence maze performance.
      Furthermore, a probe trial procedure to determine extra-maze cue utilization
      while solving the water radial arm maze established that aged female rats
      utilized extramaze cues, and that they did not rely on a nonspatial chaining
      strategy to locate hidden platforms. Galantamine treatment had no effect on use
      of extramaze cues or chaining. In addition, there were no significant changes in
      neurotrophin levels in the frontal cortex, entorhinal cortex, hippocampus, or
      basal forebrain after galantamine administration. Therefore, the data reported
      here suggest that aged animals do utilize spatial strategies for solving a
      working memory task, but galantamine has no appreciable effects on this task, at
      least not at the doses tested.

PMID- 17503734
TI  - Schwann cell transplantation improves reticulospinal axon growth and forelimb
      strength after severe cervical spinal cord contusion.
AB  - Schwann cell (SC) implantation alone has been shown to promote the growth of
      propriospinal and sensory axons, but not long-tract descending axons, after
      thoracic spinal cord injury (SCI). In the current study, we examined if an
      axotomy close to the cell body of origin (so as to enhance the intrinsic growth
      response) could permit supraspinal axons to grow onto SC grafts. Adult female
      Fischer rats received a severe (C5) cervical contusion (1.1 mm displacement, 3
      KDyn). At 1 week postinjury, 2 million SCs ex vivo transduced with lentiviral
      vector encoding enhanced green fluorescent protein (EGFP) were implanted within
      media into the injury epicenter; injury-only animals served as controls. Animals
      were tested weekly using the BBB score for 7 weeks postimplantation and received
      at end point tests for upper body strength: self-supported forelimb hanging,
      forearm grip force, and the incline plane. Following behavioral assessment,
      animals were anterogradely traced bilaterally from the reticular formation using
      BDA-Texas Red. Stereological quantification revealed a twofold increase in the
      numbers of preserved NeuN+ neurons rostral and caudal to the injury/graft site in
      SC implanted animals, corroborating previous reports of their neuroprotective
      efficacy. Examination of labeled reticulospinal axon growth revealed that while
      rarely an axon was present within the lesion site of injury-only controls,
      numerous reticulospinal axons had penetrated the SC implant/lesion milieu. This
      has not been observed following implantation of SCs alone into the injured
      thoracic spinal cord. Significant behavioral improvements over injury-only
      controls in upper limb strength, including an enhanced grip strength (a 296%
      increase) and an increased self-supported forelimb hanging, accompanied SC
      mediated neuroprotection and reticulospinal axon growth. The current study
      further supports the neuroprotective efficacy of SC implants after SCI and
      demonstrates that SCs alone are capable of supporting modest supraspinal axon
      growth when the site of axon injury is closer to the cell body of the axotomized
      neuron.

PMID- 17503735
TI  - Differential loss of presynaptic dopaminergic markers in Parkinsonian monkeys.
AB  - Assessment of dopamine nerve terminal function and integrity is a strategy
      employed to monitor deficits in Parkinson's disease (PD) patients and in
      preclinical models of PD. Dopamine replacement therapies effectively replenish
      the diminished supply of endogenous dopamine and provide symptomatic benefit to
      patients. Tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular
      monoamine transporter 2 (VMAT2), and amino acid decarboxylase (AADC) are widely
      used markers of dopaminergic neurons and terminals. The present studies were
      initiated to: (a) assess alterations in all four markers in the MPTP primate
      model of dopaminergic degeneration and (b) to determine whether L-DOPA treatment
      may itself modulate the expression of these markers. MPTP treatment induced a
      significant decline of dopaminergic immunoreactive fiber and terminal density in
      the basal ganglia. The amount of reduction varied between markers. The rank order
      of presynaptic marker loss, from most to least profound reduction, was TH > VMAT2
      > DAT > AADC. Semiquantitative image analysis of relative dopaminergic
      presynaptic fiber and terminal density illustrated region-specific reduction of
      all four markers. Double immunofluorescence colocalization of two presynaptic
      markers on the same tissue section confirmed there was a more dramatic loss of TH
      than of VMAT2 or of DAT following MPTP treatment. L-DOPA treatment was associated
      with a significantly higher level of AADC and VMAT2 immunoreactivity in the
      caudate nucleus compared to placebo. These results illustrate that neurotoxic
      injury of the dopamine system in primates leads to altered and differential
      expression of presynaptic dopaminergic markers in the basal ganglia and that
      expression of such markers may be modulated by L-DOPA therapy. These findings
      have implications for the use of biomarkers of disease progression as well as for
      the assessment of neurorestorative strategies, such as cell replacement, for the
      treatment of PD.

PMID- 17503736
TI  - The pivotal role of RhoA GTPase in the molecular signaling of axon growth
      inhibition after CNS injury and targeted therapeutic strategies.
AB  - The dogma that the adult central nervous system (CNS) is nonpermissive to axonal
      regeneration is beginning to fall in the face of increased understanding of the
      molecular and cellular biology of axon outgrowth. It is now appreciated that axon
      growth is regulated by a combination of extracellular factors related to the
      milieu of the developing or adult CNS and the presence of injury, and
      intracellular factors related to the "growth state" of the developing or
      regenerating neuron. Several critical points of convergence within the developing
      or regenerating neuron for mediating intracellular cell signaling effects on the
      growth cone cytoskeleton have been identified, and their modulation has produced
      marked increases in axon outgrowth within the "nonpermissive" milieu of the adult
      injured CNS. One such critical convergence point is the small GTPase RhoA, which
      integrates signaling events produced by both myelin-associated inhibitors (e.g.,
      NogoA) and astroglial-derived inhibitors (chondroitin sulfate proteoglycans) and
      regulates the activity of downstream effectors that modulate cytoskeletal
      dynamics within the growth cone mediating axon outgrowth or retraction.
      Inhibition of RhoA has been associated with increased outgrowth on nonpermissive
      substrates in vitro and increased axon regeneration in vivo. We are developing
      lentiviral vectors that modulate RhoA activity, allowing more long-term
      expression than is possible with current approaches. These vectors may be useful
      in regenerative strategies for spinal cord injury, brain injury, and
      neurodegenerative diseases including Parkinson's disease, Alzheimer's disease,
      and Huntington's disease.

PMID- 17503737
TI  - Plasticity of the central nervous system and formation of "auxiliary niches"
      after stem cell grafting: an essay.
AB  - It is hoped that stem cell biology will play a major role in the treatment of a
      number of so far incurable diseases via transplantation therapy. Today, we know
      that neural stem cell grafts not only represent a valuable source of missing
      cells and molecules for the host nervous system, but they also bring with them
      biological principles and processes assuring tissue plasticity and homeostasis
      found in early development and in postnatal neurogenic areas. In this review, we
      discuss the potential of grafted neural stem/progenitor cells to induce
      plasticity in the adult diseased brain by mimicking the cellular and molecular
      processes governing the biology of endogenous stem cell niches. If confirmed,
      such anlagen of "auxiliary niches" could help us to optimize intercellular
      communication in donor cell-initiated networks of graft-host interactions and to
      "rejuvenate" the adult nervous system in its response to disease and injury.

PMID- 17503738
TI  - The role of endothelial progenitor cells in ischemic cerebral and heart diseases.
AB  - Ischemic heart and cerebral diseases are complex clinical syndromes. Endothelial
      dysfunction caused by dysfunctional endothelial progenitor cells (EPCs) is
      thought to play a major role in pathophysiology of both types of disease. Healthy
      EPCs may be able to replace the dysfunctional endothelium through endogenous
      repair mechanisms. EPC levels are changed in patients with ischemic
      cerebrovascular and cardiovascular disease and EPCs may play a role in the
      pathophysiology of these diseases. EPCs are also a marker for preventive and
      therapeutic interventions. Homing of EPCs to ischemic sites is a mechanism of
      ischemic tissue repair, and molecules such as stromal-derived factor-1 and
      integrin may play a role in EPC homing in ischemic disease. Potentiation of the
      function and numbers of EPCs as well as combining EPCs with other pharmaceutical
      agents may improve the condition of ischemia patients. However, the precise role
      of EPCs in ischemic heart and cerebral disease and their therapeutic potential
      still remain to be explored. Here, we discuss the identification, mobilization,
      and clinical implications of EPCs in ischemic diseases.

PMID- 17503739
TI  - Blood-brain barrier pathology in Alzheimer's and Parkinson's disease:
      implications for drug therapy.
AB  - The blood-brain barrier (BBB) is a tightly regulated barrier in the central
      nervous system. Though the BBB is thought to be intact during neurodegenerative
      diseases such as Alzheimer's (AD) and Parkinson's disease (PD), recent evidence
      argues otherwise. Dysfunction of the BBB may be involved in disease progression,
      eliciting of peripheral immune response, and, most importantly, altered drug
      efficacy. In this review, we will give a brief overview of the BBB, its
      components, and their functions. We will critically evaluate the current
      literature in AD and PD BBB pathology resulting from insult, neuroinflammation,
      and neurodegeneration. Specifically, we will discuss alterations in tight
      junction, transport and endothelial cell surface proteins, and vascular density
      changes, all of which result in altered permeability. Finally, we will discuss
      the implications of BBB dysfunction in current and future therapeutics.
      Developing a better appreciation of BBB dysfunction in AD and PD may not only
      provide novel strategies in treatment, but will prove an interesting milestone in
      understanding neurodegenerative disease etiology and progression.

PMID- 17503740
TI  - Huntington's disease: pathological mechanisms and therapeutic strategies.
AB  - Huntington's disease (HD) is a devastating neurodegenerative disorder that occurs
      in patients with a mutation in the huntingtin or IT15 gene. Patients are plagued
      by early cognitive signs, motor deficits, and psychiatric disturbances. Symptoms
      are attributed to cell death in the striatum and disruption of cortical-striatal
      circuitry. Mechanisms of cell death are unclear, but processes involving
      mitochondrial abnormalities, excitotoxicity, and abnormal protein degradation
      have been implicated. Many factors likely contribute to neuron death and
      dysfunction, and this has made it difficult to systematically address the
      pathology in HD. Pharmaceutical therapies are commonly used in patients to treat
      disease symptoms. These have limited benefit and do not address the inexorable
      disease progression. Several neuroprotective therapies are being evaluated in
      animal models of HD as well as in clinical trials. Similarly, cell replacement
      strategies such as fetal transplantation have been used in the clinic with
      minimal success, making future cell replacement strategies such as stem cell
      therapy uncertain. This review describes the disease pathology in HD and
      addresses many of the past and emerging therapeutic strategies.

PMID- 17503741
TI  - Inhibition of Simian virus 40 large T antigen helicase activity by
      fluoroquinolones.
AB  - BACKGROUND: Fluoroquinolones represent a potent group of antibiotics that inhibit
      bacterial DNA replication by targeting the essential bacterial enzymes gyrase and
      topoisomerase IV. Inhibition of gyrase activity by quinolones involves the
      interaction of these drugs with the helicase component of bacterial gyrase. DNA
      tumour viruses also encode helicases that are essential for their DNA replication
      in the host. METHODS: In this study we have evaluated the effect of
      fluoroquinolones on viral DNA replication using the DNA tumour virus Simian virus
      40 (SV40) as our model. Four different fluoroquinolones, namely, levofloxacin,
      trovafloxacin, ciprofloxacin and ofloxacin, were tested for their ability to
      inhibit viral DNA replication. RESULTS: We show here that all four quinolones
      tested were effective in the inhibition of SV40 plaque formation and DNA
      replication in CV1-P cells. In addition, we found that each of these quinolones
      was inhibitory to the helicase activity of SV40 large tumour antigen.
      CONCLUSIONS: Fluoroquinolones and their derivates may therefore be useful in the
      treatment and/or prevention of infection by SV40-homologous human DNA viruses
      that encode helicase activity for their survival.

PMID- 17503742
TI  - Comparison of mass spectrometric analysis and TRUGENE HBV genotyping for
      monitoring lamivudine resistance in chronic hepatitis B patients.
AB  - BACKGROUND: There is an increasing need for the early detection of emerging
      mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of
      hepatitis B virus (HBV) DNA polymerase with using sensitive molecular methods.
      METHODS: We evaluated the usefulness of monitoring lamivudine resistance using a
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      based assay (the restriction fragment mass polymorphism; RFMP) in comparison with
      the direct sequencing assay, the TRUGENE ' HBV genotyping kit. We also
      investigated the treatment responses in relation to the presence of YMDD mutants.
      The sera from 50 chronic HBVs patients were analysed for the presence of YMDD
      mutants by performing RFMP and TRUGENE. The results at codons 180 and 204 were
      compared for 46 patients. RESULTS: The concordance rate between the two assays
      was 65.2% (30/46). All the discordance corresponded to the detection of
      additional virus populations by RFMP. Early detection of mutants before viral
      breakthrough was accomplished by RFMP in two patients. Persistence of very low
      viraemia was observed in five patients who harboured mutant virus populations.
      Additional information was provided by TRUGENE in eight patients. CONCLUSIONS:
      RFMP showed a superior ability for detecting minor mutant virus populations
      compared with TRUGENE. However, the results of highly sensitive RFMP should be
      interpreted carefully because lamivudine could be effective despite the presence
      of mutants. RFMP could be a practical tool in conjunction with regular
      measurements of the HBV viral load for the early detection of lamivudine
      resistance and the timely introduction of new antiviral drugs.

PMID- 17503743
TI  - The development of artificial neural networks to predict virological response to
      combination HIV therapy.
AB  - INTRODUCTION: When used in combination, antiretroviral drugs are highly effective
      for suppressing HIV replication. Nevertheless, treatment failure commonly occurs
      and is generally associated with viral drug resistance. The choice of an
      alternative regimen may be guided by a drug-resistance test. However,
      interpretation of resistance from genotypic data poses a major challenge.
      METHODS: As an alternative to current interpretation systems, we have developed
      artificial neural network (ANN) models to predict virological response to
      combination therapy from HIV genotype and other clinical information. RESULTS:
      ANN models trained with genotype, baseline viral load and time to follow-up viral
      load (1154 treatment change episodes from multiple clinics), produced predictions
      of virological response that were highly significantly correlated with actual
      responses (r2 = 0.53; P < 0.00001) using independent test data from clinics that
      contributed training data. Augmented models, trained with the additional
      variables of baseline CD4+ T-cell count and four treatment history variables,
      were more accurate, explaining 69% of the variance in virological response.
      Models trained with the full input dataset, but only those data involving highly
      active antiretroviral therapy (three or more full-dose antiretroviral drugs in
      combination), performed at an intermediate level, explaining 61% of the variance.
      The augmented models performed less well when tested with data from unfamiliar
      clinics that had not contributed data to the training dataset, explaining 46% of
      the variance in response. CONCLUSION: These data indicate that ANN models can be
      quite accurate predictors of virological response to HIV therapy even for
      patients from unfamiliar clinics. ANN models therefore warrant further
      development as a potential tool to aid treatment selection.

PMID- 17503744
TI  - Evolution of resistance mutations during low-level viral replication in HIV-1
      infected patients treated with zidovudine/lamivudine/abacavir as a first-line
      regimen.
AB  - OBJECTIVE: Long-term evaluation of viral evolution in patients who continued
      first-line therapy with zidovudine/lamivudine/abacavir (Trizivir [TZV]) in the
      presence of low-level viral replication and assessment of the impact of
      mutational patterns selected under TZV on viral load (VL), CD4+ T-cell count
      (CD4) and subsequent therapeutic options. DESIGN: Analysis of viral evolution
      based on genotypic resistance tests (GRT) from samples collected during non
      suppressive first-line therapy with TZV. METHODS: Patients from the Frankfurt HIV
      cohort with at least 3 months uninterrupted first-line therapy with TZV in whom
      VL and CD4 measurements were performed at baseline and at follow up were
      identified. Criteria for virological failure (VF) were two consecutive VL >400
      copies/ml. GRTs were required at baseline, VF and last visit (LV). RESULTS:
      Initially, 23/119 patients were classified as VF; 4/23 were lost to follow up.
      Median time to VF was 48 weeks. Because of the observed virological and
      immunological benefit, patients continued TZV for a median of 87 weeks despite
      detectable viraemia. Median CD4 increase and VL reduction at LV were 120
      cells/mm3 and 317,100 copies/ml, respectively, compared to baseline. After 54
      weeks of treatment with detectable VL, three mutational patterns were observed:
      Group A (n=4) characterized by M184V without further regimen-associated
      mutations, group B (n=9) by M184V accompanied by one to three thymidine analogue
      mutations (TAMs), and group C (n=6) by M184V and four to six TAMs. No virological
      or CD4 parameters correlated with these patterns. Group A remained unchanged,
      thus preserving activity of most nucleoside analogues (NA). However, in the
      majority of patients (groups B and C) accumulation of mutations at different
      rates was observed, leading to a sequential loss of NA options. CONCLUSIONS:
      Continuous treatment with TZV in the presence of viral replication is associated
      with a stepwise accumulation of resistance mutations. M184V was present in all
      cases, not followed by further selection of TAMs in a small, unpredictable
      subgroup of patients. However, in the majority of patients selection of M184V was
      associated with accumulation of TAMs at different rates leading to a substantial
      loss of active NAs, despite continuous virological and immunological benefit when
      compared with baseline.

PMID- 17503745
TI  - Renal function in antiretroviral-experienced patients treated with tenofovir
      disoproxil fumarate associated with atazanavir/ritonavir.
AB  - OBJECTIVE: To determine the evolution of renal function in highly treatment
      experienced patients with normal renal function at baseline receiving tenofovir
      disoproxil fumarate (TDF) as part of a fixed combined antiretroviral regimen and
      to identify prognostic factors of change in renal function, including tenofovir
      concentrations. METHODS: A prospective 48-week open-label trial was carried out,
      evaluating the safety of TDF, associated with atazanavir/ritonavir, and optimized
      nucleoside reverse transcriptase inhibitors, in patients with documented failure
      in previous treatments. Statistical analysis was performed on an intent-to-treat
      basis. RESULTS: Fifty-three patients were included, with a median CD4+ T-cell
      count of 206 x 10(6)/l and a median HIV RNA level of 5 log10 copies/ml. All
      patients had normal serum creatinine levels and creatinine clearances (CL(Cr)) at
      baseline, which were stable within the 2 months preceding inclusion. Two patients
      discontinued TDF as a result of severe renal impairment. Two patients never
      started TDF. A total of 49 patients without clinical nephrotoxicity were
      analysed. The median creatinine level increased significantly from baseline to
      week 48 (+0.04 mg/dl [+5.8%]; P = 0.008), and the median CL(Cr) decreased
      significantly (-7.8 ml/min [-7.6%]; P = 0.005). Trough tenofovir concentration
      was not associated with change in CL(Cr), (P = 0.79). No risk factors, including
      tenofovir plasma trough levels, were significantly associated with change in
      CL(Cr) at week 24. CONCLUSIONS: This study confirms that TDF-related severe
      nephrotoxicity is an uncommon event. In patients without clinical nephrotoxicity,
      the use of TDF during a 1-year period was associated with a slight but
      significant alteration of renal function, which was not associated with increased
      trough concentration.

PMID- 17503746
TI  - Adefovir dipivoxil monotherapy and combination therapy with lamivudine for the
      treatment of chronic hepatitis B in an Asian population.
AB  - AIM: To determine differences in Chinese patients treated with adefovir (ADV)
      monotherapy or ADV in combination with lamivudine (3TC) after development of
      resistance to 3TC, with respect to biochemical improvement, HBV DNA suppression
      and development of subsequent ADV resistance. METHODS: All hepatitis B patients
      with 3TC resistance treated with ADV for 3 months or more at our centre were
      included, and monitored 3-6 monthly for biochemical and virological response, and
      development of ADV resistance. RESULTS: A total of 56 patients were included, 50%
      switched to ADV monotherapy and 50% received combination 3TC/ADV therapy. Median
      follow-up was 15.5 months. Normalization of alanine aminotransferase (ALT)
      occurred in 25 (89%) patients in the ADV group compared with 24 (86%) in the
      3TC/ADV group (P = 0.686). Virological response (VR) was achieved in seven (35%)
      patients in the ADV group at 12 months compared with five (28%) in the 3TC/ADV
      group (P = 0.637). By 24 months, seven (64%) patients in the ADV group achieved
      VR compared with two (40%) in the 3TC/ADV group (P = 0.377). Cumulative
      probability of developing genotypic ADV resistance in the ADV group at 24 months
      was 18% compared with 7% in the 3TC/ADV group (P = 0.94). CONCLUSION: There was
      no obvious improvement in ALT normalization and virological suppression or
      reduction in the development of ADV-resistant mutations with 3TC/ADV therapy
      compared with ADV monotherapy. Further studies with longer follow-ups are
      required to determine whether combination 3TC/ADV therapy will reduce the
      emergence of ADV resistance compared with ADV monotherapy.

PMID- 17503747
TI  - A virological benefit from an induction/maintenance strategy: the Forte trial.
AB  - OBJECTIVE: To evaluate whether the addition of a fourth drug for up to 32 weeks
      to a standard three-drug antiretroviral combination decreases the risk of
      virological failure without increasing toxicity in treatment-naive patients.
      DESIGN: Induction/maintenance (IM) therapy [two nucleoside reverse transcriptase
      inhibitors (NRTIs) + one non-NRTI (NNRTI) + one protease inhibitor for 24-32
      weeks until plasma HIV RNA viral load (VL) < or =50 copies/ml then two NRTIs +
      NNRTI] was compared with standard therapy (ST) (two NRTIs + NNRTI). The primary
      endpoint was virological failure: VL >50 copies/ml at 32 (and 24) weeks or
      subsequent rebound to >400 copies/ml. RESULTS: 122 (62 IM, 60 ST) participants
      were randomized and followed for a median of 81 weeks (IQR 64-145). 52% were
      asymptomatic; median CD4+ T-cell count was 160 x 10(6)/l (IQR 92-260) and median
      VL 98,830 copies/ml (IQR 37,500-241,290). In an intent-to-treat analysis, the
      proportion of participants with virological failure at or after 32 weeks was
      higher in the ST arm [26 (43%) versus 11 (18%), P = 0.002]. The mean decrease in
      VL at 48 weeks was 0.84 95% confidence interval (CI) (0.15, 1.53) log10 copies/ml
      greater in the IM arm (P = 0.02). There were no significant differences between
      the two arms in the change in CD4+ T-cell count from baseline to 48 weeks, the
      number of participants with adverse events or the frequency of progression to
      AIDS/death. Drug resistance at failure was detected less frequently in the IM
      arm. CONCLUSIONS: Starting antiretroviral therapy with an IM strategy improved
      virological outcomes compared with a three-drug regimen, without significantly
      increasing toxicity.

PMID- 17503748
TI  - A computer-based system to aid in the interpretation of plasma concentrations of
      antiretrovirals for therapeutic drug monitoring.
AB  - OBJECTIVES: To develop a computer-based system for modelling and interpreting
      plasma antiretroviral concentrations for therapeutic drug monitoring (TDM).
      METHODS: Data were extracted from a prospective TDM study of 199 HIV-infected
      patients (CCTG 578). Lopinavir (LPV) and efavirenz (EFV) pharmacokinetic (PK)
      parameters were modelled using a Bayesian method and interpreted by an expert
      committee of HIV specialists and pharmacologists who made TDM recommendations.
      These PK models and recommendations formed the knowledge base to develop an
      artificial intelligence (AI) system that could estimate drug exposure, interpret
      PK data and generate TDM recommendations. The modelled PK exposures and expert
      committee TDM recommendations were considered optimum and used to validate
      results obtained by the AI system. RESULTS: A group of patients, 67 on LPV, 46 on
      EFV and three on both drugs, were included in this analysis. Correlations were
      high for LPV and EFV estimated trough and 4 h post-dose concentrations between
      the Al estimates and modelled values (r > 0.79 for all comparisons; P < 0.0001).
      Although trough concentrations were similar, significant differences were seen
      for mean predicted 4 h concentrations for EFV (4.16 microg/ml versus 3.89
      microg/ml; P = 0.02) and LPV (7.99 microg/ml versus 8.79 microg/ml; P < 0.001).
      The AI and expert committee TDM recommendations agreed in 53 out of 69 LPV cases
      [kappa (kappa) = 0.53; P < 0.001] and 47 out of 49 EFV cases (kappa = 0.91; P <
      0.001). CONCLUSION: The AI system successfully estimated LPV and EFV trough
      concentrations and achieved good agreement with expert committee TDM
      recommendations for EFV- and LPV-treated patients.

PMID- 17503749
TI  - Evaluation of cytomegalovirus DNAaemia versus pp65-antigenaemia cutoff for
      guiding preemptive therapy in transplant recipients: a randomized study.
AB  - METHODS: A bicentre, randomized, prospective open-label study aimed at defining a
      DNAaemia versus antigenaemia cutoff for guiding preemptive therapy of human
      cytomegalovirus (HCMV) infections in solid organ transplant recipients (SOTR) was
      completed. Overall, 99 patients were enrolled in the DNAaemia arm and 101
      patients in the antigenaemia arm. Patients were randomized to be monitored for
      HCMV infection in the blood by either assay. Antiviral treatment was started in
      both seropositive and seronegative patients when levels greater than 300,000 DNA
      copies/ml blood or 100 pp65-positive leukocytes in the relevant arm were reached.
      RESULTS: HCMV infection was detected in 81/99 (81.8%) patients in the DNAaemia
      arm and in 87/101 (86.1%) patients in the antigenaemia arm (P=ns). Antiviral
      treatment was given to 23/99 (23.0%) patients in the DNAaemia arm and 42/101
      (41.0%) patients in the antigenaemia arm (P = 0.01). In the DNAaemia arm,
      antiviral therapy was significantly delayed and duration of the first course of
      treatment was significantly greater than in the antigenaemia arm. However, total
      duration of treatment was comparable in the two arms. No case of HCMV disease
      occurred in patients treated after reaching the relevant cutoff. However, four
      patients (three in the antigenaemia arm, and one in the DNAaemia arm) suffered
      from HCMV disease prior to reaching the relevant cutoff. CONCLUSIONS: Compared
      with antigenaemia, a single DNAaemia cutoff: (i) significantly reduces the number
      of patients requiring treatment; (ii) may be safely adopted to guide preemptive
      therapy of both primary and reactivated HCMV infections in SOTR; and (iii) does
      not significantly modify the overall duration of treatment.

PMID- 17503750
TI  - Prediction of treatment-related HBsAg loss in HBeAG-negative chronic hepatitis B:
      a clue from serum HBsAg levels.
AB  - BACKGROUND: Quantification of HBsAg in serum may be of clinical importance in
      predicting HBsAg seroconversion and complete response to treatment. METHODS:
      Serum HBsAg was quantified by ADVIA Centaur in 63 patients with HBeAg-negative
      chronic hepatitis B (CHBe-). A total of 42 had received interferon-alpha2b (IFN
      alpha2b) (median 12.1 months; 19 sustained responders including 12 HBsAg
      seroconvertors; 23 non-sustained responders) and 21 were on lamivudine (LAM)
      (median 33.0 months). Measurements were done at baseline, during and at the end
      of treatment, and during and at the end of follow-up. RESULTS: Baseline median
      [interquartile range (IQR)] HBsAg levels in all patients were 3286 (1602-7458)
      IU/ml, not different between IFN- and LAM-treated (P = 0.139). IFN significantly
      depressed HBsAg in all patients except IFN non-responders, but HBsAg decline
      persisted only in sustained responders. Low pretreatment HBsAg level was the only
      significant prognostic variable of HBsAg seroconversion by multivariate analysis.
      LAM treatment also suppressed HBsAg levels but at a significantly slower rate
      compared with IFN (P = 0.022). The median (IQR) estimated time to HBsAg
      undetectability (ETU-HBsAg), derived from best curve fitting, was 127 (87.6
      263.5) months for LAM virological responders and 65.3 (36.3-95.0) months for IFN
      sustained responders (P = 0.002). In 12 HBsAg seroconvertors, ETU-HBsAg was
      similar to the real time of HBsAg loss (P = 0.525) and seroconversion (0.056).
      CONCLUSIONS: In CHBe-, IFN induces a sharper decrease in serum HBsAg compared
      with LAM and low pretreatment levels are significantly associated with HBsAg
      serocon-version. Serial HBsAg measurements may be useful for prediction of HBsAg
      loss and our data suggest that to achieve this, 5.4 years of sustained response
      to IFN or 10.6 years of effective LAM therapy are probably needed.

PMID- 17503751
TI  - Conservation of first-line antiretroviral treatment regimen where therapeutic
      options are limited.
AB  - OBJECTIVES: To determine rates and causes of switching from first- to second-line
      antiretroviral treatment (ART) regimens in a large treatment-naive cohort (a
      South African community-based ART service) where a targeted adherence
      intervention was used to manage initial virological breakthrough. METHODS: ART
      naive adults (n=929) commencing first-line non-nucleoside-based ART [according to
      WHO (2002) guidelines] between September 2002 and August 2005 were studied
      prospectively. Viral load (VL) and CD4+ T-cell counts were monitored every 4
      months. All drug switches were recorded. Counsellor-driven adherence
      interventions were targeted to patients with a VL > 1000 copies/ml at any visit
      (virological breakthrough) and the VL measurement was repeated within 8 weeks.
      Two consecutive VL measurements > 1000 copies/ml was considered virological
      failure, triggering change to a second-line regimen. RESULTS: During 760 person
      years of observation [median (IQR) 189 (85-441) days], 823 (89%) patients were
      retained on ART, 2% transferred elsewhere, 7% died and 3% were lost to follow-up.
      A total of 893 (96%) patients remained on first-line therapy and 16 (1.7%)
      switched to second-line due to hypersensitivity reactions (n=9) or lactic
      acidosis (n=7). A Kaplan-Meier estimate for switching to second-line due to
      toxicity was 3.0% at 32 months. Virological breakthrough occurred in 67 (7.2%)
      patients, but, following use of a targeted adherence intervention, virological
      failure was confirmed in just 20 (2.2%). Kaplan-Meier estimates at 32 months were
      20% for virological breakthrough but only 5.6% for confirmed virological failure.
      CONCLUSION: Regimen switches were due to virological failure or toxicity.
      Although follow-up time was limited, over 95% of individuals remained on first
      line ART using a combination of viral monitoring and a targeted adherence
      intervention.

PMID- 17503752
TI  - Frequency, determinants and consequences of delayed access to care for HIV
      infection in France.
AB  - BACKGROUND AND OBJECTIVES: We analysed the frequency and predictors of delayed
      access to care (DAC) for HIV infection, and its influence on survival. METHODS:
      We studied predictors of DAC among 18,721 patients enrolled between 1997 and 2002
      in the French Hospital Database on HIV (FHDH), DAC being defined by a CD4* T-cell
      count below 200 copies/mm3 and/or AIDS at FHDH enrollment. The association of DAC
      with the initiation of combined antiretroviral therapy (cART) and of DAC with
      survival were analysed with Cox multivariable models. RESULTS: The overall
      prevalence of DAC was 35.7%. Compared with patients under 30 years of age,
      patients over 60 were 3.5 times more likely to have DAC (P < 10(-4)). Compared
      with non-migrant women, odds ratios (OR) of DAC were higher among migrant women
      (1.5), non-migrant men (1.6) and migrant men (1.9; all P < 10(-4)). Compared with
      men who have sex with men, other transmission groups had an estimated OR for DAC
      of 1.6 (P < 10(-4)). DAC was more frequent among patients with a recent diagnosis
      of HIV infection [OR = 1.3, 95% confidence intervals (CI) = (1.2;1.4)]. Patients
      with DAC received cART earlier than other patients [hazard ratio (HR) = 2.2, 95%
      CI = (2.1;2.3)]. The DAC/mortality HR was 13.9 in the first 6 months after
      enrollment in the FHDH, and remained significantly higher than 1 during the
      subsequent 4 years. CONCLUSION: DAC is common in France and was associated with a
      higher mortality, despite early initiation of cART. Earlier access to care and
      specific clinical management of patients with DAC should be considered.

PMID- 17503753
TI  - Uridine supplementation for the treatment of antiretroviral therapy-associated
      lipoatrophy: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) is associated with loss
      of subcutaneous fat (lipoatrophy) presumably due to mitochondrial toxicity of
      nucleoside reverse transcriptase inhibitors. In vitro, uridine abrogates
      thymidine analogue-induced toxicity in adipocytes. METHODS: A total of 20
      patients with HAART-associated lipoatrophy were randomized to receive either a
      dietary uridine supplement (36 g three times a day for 10 consecutive days/month)
      or placebo, for 3 months. Body composition was measured using dual energy X-ray
      absorptiometry, magnetic resonance imaging and proton spectroscopy. Data are mean
      +/- standard error of mean. RESULTS: The mean increases in limb fat (880 +/- 140
      versus 230 +/- 270 g; P < 0.05), intra-abdominal fat (210 +/- 80 versus -80 +/-
      70 cm3; P < 0.05) and total body fat (1920 +/- 240 versus 240 +/- 520 g; P <
      0.01) were significantly greater in the uridine than in the placebo group. Within
      the uridine group, the changes from baseline to 3 months were statistically
      significant in total limb fat (P < 0.001), intra-abdominal fat (P < 0.05) and
      total body fat (P < 0.001). The proportion of limb fat to total fat increased
      from 18% to 25% (P < 0.05) in the uridine group. Liver fat content and lean body
      mass remained unchanged in both groups. High-density lipoprotein-cholesterol
      concentrations decreased in the uridine and increased in the placebo group,
      whereas fasting serum insulin concentrations did not change. Uridine
      supplementation was well tolerated and the virological effect of HAART was not
      affected. CONCLUSION: Uridine supplementation significantly and predominantly
      increased subcutaneous fat mass in lipoatrophic HIV-infected patients during
      unchanged HAART.

PMID- 17503754
TI  - HIV-1 drug resistance surveillance using dried whole blood spots.
AB  - BACKGROUND: Field-friendly methods for HIV drug resistance (HIVDR) surveillance
      in resource-limited regions are urgently needed. Despite evidence that dried
      blood spots (DBS) are suitable for HIV serology, viral load and CD4+ T-cell
      enumeration, no study has evaluated DBS for HIVDR genotyping. We assessed the
      feasibility of genotyping HIV-1 from field-collected DBS stored under challenging
      environmental conditions. METHODS: We prospectively collected specimens from
      newly diagnosed, treatment-naive HIV-positive subjects in Mexico. Whole blood was
      spotted onto filter cards, air dried at ambient temperature and stored with
      desiccant at 37 degrees C and 85% humidity for 3 months. Genotypes obtained from
      DBS-extracted nucleic acids using an in-house nested reverse transcription-PCR
      method were compared to genotypes derived from matched plasma. RESULTS: Genotypes
      from 103 phylogenetically matched plasma and DBS were compared. In total, 90.1%
      of all DBS specimens could be amplified in either the region of HIV protease or
      the region of reverse transcriptase. Failure to amplify from DBS did not
      correlate with low plasma viral loads. Between paired specimens, the median
      nucleotide similarity was 99.95%. In the nine specimens with drug resistance
      mutations, all differences between pairs were partial discordances. Mutations
      identified in plasma were found in the majority of replicate DBS amplifications.
      CONCLUSION: The results suggest that genotypes obtained from DBS are equivalent
      to those from plasma. DBS are a promising public health tool for HIVDR
      surveillance of treatment-naive subjects, especially in regions where specimens
      might be exposed to severe environmental conditions and where logistical
      difficulties could prevent timely specimen processing. More studies are needed to
      validate DBS for patient monitoring.

PMID- 17503755
TI  - Does tenofovir influence efavirenz pharmacokinetics?
AB  - INTRODUCTION: A recent report described a possible interaction between tenofovir
      (TFV) and efavirenz (EFV). Patients developed neuropsychiatric manifestations
      upon introduction of TFV on a stable EFV-containing regimen. We evaluated the
      possibility of a pharmacokinetic interaction between TFV and EFV by assessing
      cross-sectional and longitudinal data in 169 individuals receiving EFV. RESULTS:
      EFV plasma area-under-the-curve (AUC) levels were comparable among individuals
      receiving (n=18) or not receiving TFV (n=151); 57,962 versus 52,293 ng*h/ml.
      However, under conditions of limited EFV metabolism, that is, the group of 23
      individuals carrying two copies of CYP2B6 loss/diminished-function alleles,
      plasma AUC values were highest among individuals receiving TFV (n=5, 353,031
      ng*h/ml), compared with those not receiving TFV (n=18, 180,689 ng*h/ml).
      Statistical analysis identified both a global, sixfold effect of CYP2B6
      loss/diminished function (P < 0.0001) and a significant interaction between the
      number of loss/diminished-function alleles and the co-medication with TFV (P =
      0.009). CONCLUSION: Although there is no clear evidence for a pharmacokinetic
      interaction between TFV and EFV, we cannot rule out an interaction between these
      drugs restricted to individuals who are slow EFV metabolizers.

PMID- 17503756
TI  - Improvements in parameters of end-stage liver disease in patients with HIV/HBV
      related cirrhosis treated with tenofovir.
AB  - BACKGROUND: Mortality related to end-stage liver disease is increasing in
      HIV/hepatitis B virus (HBV)-coinfected patients and effective treatment options
      are limited. Tenofovir is now widely used in HIV/HBV coinfection and results in
      significant HBV suppression, in both patients with and patients without
      lamivudine resistance. The safety and efficacy of tenofovir in HIV/HBV cirrhosis
      has not been previously described. METHODS: Seven cirrhotic HIV/HBV patients
      treated with tenofovir were identified within the HIV clinic. Parameters of
      hepatic function, CD4+ T-cell counts, HBV DNA levels and Child-Pugh Class (C-P-C)
      were determined before and after addition of tenofovir. All patients had prior
      lamivudine experience with a median baseline HBV DNA of 6.23 x 10(7) copies/ml.
      RESULTS: Four of seven patients were C-P-C -A and hepatitis 'e' antigen (HBeAG)
      was positive in 4/7 patients. After a median duration of tenofovir of 28 months,
      all laboratory parameters improved, with significant changes in albumin and
      prothrombin (PT) (median pre/post-tenofovir: alanine aminotransferase 63/39;
      bilirubin 26/18; albumin 39/44, P = 0.028; PT 17.5/15, P = 0.018). All three
      patients with C-P-C -B or -C improved to C-P-C -A, which for one patient enabled
      removal from the liver transplant waiting list. Three patients lost HBeAG with
      two anti-HBe seroconversions. Median HBV DNA was suppressed to <35 copies/mi.
      CONCLUSIONS: This study demonstrates that tenofovir can produce HBV viral
      suppression, HBeAg seroconversion and improvement in markers of hepatic function
      in HIV/HBV-coinfected patients with cirrhosis. The potential reversal of end
      stage liver disease may provide an important survival benefit in this population.

PMID- 17503757
TI  - Genetic diversity and drug resistance mutations in HIV type 1 from untreated
      patients in Bamako, Mali.
AB  - OBJECTIVE: To determine the genetic diversity of HIV-1 reverse transcriptase (RT)
      and protease sequences and the presence of mutations linked to antiretroviral
      (ARV) resistance in treatment-naive, HIV-1-infected individuals living in Mali.
      METHODS: Ninety-eight samples from ARV drug-naive, HIV-1-infected patients were
      collected in one clinical centre in Bamako, Mali in 2005. RT and protease genes
      were sequenced in order to perform phylogenetic and resistance analyses. RESULTS:
      The most prevalent subtype was CRF02-AG (75% of cases), followed by the CRF06-cpx
      subtype (20%). Intersubtype recombinants between CRF02-AG, CRF01-AE and CRF06-cpx
      were also described in 5% of cases. After 4 years of ARV use in Mali, two
      previously untreated individuals (2%; 95% CI: 0.00-4.77%) were found to have
      resistant viruses, one with a single nucleoside mutation and one with K103N non
      nucleoside reverse transcriptase inhibitor resistance mutation. No evidence of
      transmitted protease inhibitor resistance mutations was found. CONCLUSION: These
      data provide direct evidence for the circulation of HIV-1 isolates containing
      resistance mutations in treatment-naive patients in Mali. Since ARV use in Mali
      began, more than 5000 patients have started treatment, mostly with Triomune
      (stavudine/lamivudine/nevirapine). The resistance-associated mutations detected
      in the present study are consistent with this treatment regimen. Continued
      surveillance will be required to monitor the emergence of ARV resistance in this
      country.

PMID- 17503758
TI  - Key reports from the XV International HIV Drug Resistance Workshop 2006.
AB  - The XV International HIV Drug Resistance Workshop recorded advances in basic and
      clinical science of HIV resistance to antiretrovirals as well as new findings on
      resistance by hepatitis B virus (HBV) and hepatitis C virus (HCV). In the
      clinical arena, attendees learned of four cases of resistance to
      lopinavir/ritonavir monotherapy, correlation between low-frequency pretreatment
      mutations and failure of a first antiretroviral regimen, emergence of non
      nucleoside-related mutations in 20% of patients interrupting a suppressive
      nonnucleoside regimen, and evolution of mutations conferring resistance to an HIV
      entry inhibitor that is being studied as a vaginal microbicide. New data reported
      from the POWER 1, 2 and 3 salvage trials suggested that there is a close
      correlation between darunavir (TMC114) phenotypic susceptibility, the number of
      baseline protease inhibitor-related resistance mutations and virological
      response. Scientists exploring the mechanisms of resistance reported of mutations
      in the carboxy-terminal domain of reverse transcriptase that may further
      resistance to zidovudine, novel mutations that may contribute to resistance of
      both nucleoside and non-nucleoside reverse transcriptase inhibitors, and a
      mechanism that HCV and HIV may share to resist antiviral therapy.

PMID- 17503760
TI  - 99mTc(CO)3-15-[N-(Acetyloxy)-2-picolylamino]pentadecanoic acid: a potential
      radiotracer for evaluation of fatty acid metabolism.
AB  - 99mTc(CO)3-15-[N-(Acetyloxy)-2-picolylamino]pentadecanoic acid (1a) was prepared
      by incorporating [99mTc(CO)3]+ into 15-[N-(hydroxycarbonylmethyl)-2
      picolylamino]pentadecanoic acid (2a). The overall radiochemical yield of 1a after
      HPLC purification was 60-63%. Radiotracer 1a was found to be chemically stable
      when incubated in human plasma for 4 h at 37 degrees C. Tissue distribution
      studies showed that high radioactivity accumulated in the heart with rapid
      clearance. The maximum heart-to-blood uptake ratio was 1.87 at 5 min after a tail
      vein injection. Radioactive metabolites were analyzed in urine samples of mice
      and corresponded to a 9.3:1 ratio of 99mTc(CO)3-5-[N-(acetyloxy)-2
      picolylamino]pentanoic acid (1b) to 99mTc(CO)3-3-[N-(acetyloxy)-2
      picolylamino]propionic acid (1c), indicating that 1a is mainly metabolized to 1b
      via beta-oxidation in the body. These results suggest that 1a is a promising
      radiotracer for evaluation of fatty acid metabolism in myocardium.

PMID- 17503761
TI  - In vitro and in vivo evaluation of 64Cu-labeled DOTA-linker-bombesin(7-14)
      analogues containing different amino acid linker moieties.
AB  - The gastrin-releasing peptide receptor (GRPR) is overexpressed on a variety of
      tumor types and has been targeted with radiolabeled peptides for detection and
      therapy of these cancers. Analogues of the 14 amino acid bombesin (BN) peptide
      have been radiolabeled with both gamma- and positron-emitting radionuclides for
      detection of GRPR-expressing tumors. We have previously evaluated BN analogues
      radiolabeled with the positron-emitter, copper-64 (64Cu), that contained various
      aliphatic linkers placed between the BN peptide and the 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator. These studies
      showed that the analogues could be used for positron-emission tomographic (PET)
      imaging of GRPR-positive tumors in mice but clinical translation would be
      hindered by significant uptake in background tissues. Therefore, the purpose of
      this study was to determine if the use of amino acid linkers placed between the
      DOTA chelate and the BN peptide would reduce nontarget tissue uptake, while
      maintaining good prostate tumor uptake. The linkers studied utilized three amino
      acid combinations of glycine (G), serine (S), or glutamic acid (E). In vitro
      assays in PC-3 cells showed that the glutamic acid-containing linkers had poor
      binding and internalization, while the other analogues had IC50 values <100 nM
      and good internalization. In vivo, these same analogues demonstrated tumor
      specific uptake and good imaging characteristics that were comparable to, or
      better than the previously reported 64Cu-labeled DOTA-BN analogues. Overall, this
      study shows that BN analogues containing amino acid linkers can be used for the
      PET imaging of GRPR-expressing prostate cancer and that these linkers lead to
      lower background tissue uptake.

PMID- 17503762
TI  - Atypical protonation states in the active site of HIV-1 protease: a computational
      study.
AB  - The HIV protease (HIVP) is a prominent example for successful structure-based
      drug design. Besides its pharmaceutical impact, it is a well-studied system for
      which, as experimentally evidenced, protonation changes in the active site occur
      upon ligand binding. Therefore, it serves as an ideal candidate for a case study
      using our newly developed partial charge model, which was optimized toward the
      application of Poisson-Boltzmann based pK(a) calculations. The charge model
      suggests reliably experimentally determined protonation states in the active site
      of HIVP. Furthermore, we perform pKa calculations for two HIVP complexes with
      novel types of inhibitors developed and synthesized in our group. For these
      complexes, no experimental knowledge about the protonation states is given. For
      one of the compounds, containing a central pyrrolidine ring, the calculations
      predict that both catalytic aspartates should be deprotonated upon ligand
      binding.

PMID- 17503763
TI  - Internal structure of wet and dry polypeptide multilayer nanofilms.

PMID- 17503764
TI  - Kinetics of acrylamide formation/elimination reactions as affected by water
      activity.
AB  - The influence of water activity on the kinetics of acrylamide formation and
      elimination reaction was investigated using low-moisture equimolar asparagine
      glucose model systems, which were heated at temperatures between 120 and 200
      degrees C for variable heating times. To determine the water content
      corresponding to the water activities tested, a sorption moisture isotherm was
      constructed experimentally. The acrylamide concentrations measured at different
      water activities could be modeled on the basis of a reaction scheme including not
      only acrylamide formation and elimination reactions but also an alternative
      Maillard reaction between both reactants. The corresponding rate constants and
      activation energies were estimated using nonlinear regression analysis. Whereas
      the rate constant for acrylamide formation varied only slightly with the initial
      water activity of the model system, the elimination rate constant showed a clear
      minimum around a water activity of 0.82. The opposite trend, namely, a maximum at
      a water activity of 0.82, was found for the Maillard reaction rate constant as a
      function of water activity, which confirms data from literature. The activation
      energies for the different reactions changed in a comparable way as the
      corresponding rate constant with water activity.

PMID- 17503765
TI  - Approach to detection in laser-induced breakdown spectroscopy.
AB  - Gated detection with intensified detectors, e.g., ICCDs, is today the accepted
      approach for detection of plasma emission in laser-induced breakdown spectroscopy
      (LIBS). However, these systems are more cost-intensive and less robust than
      nonintensified CCDs. The objective of this paper is to compare, both
      theoretically and experimentally, the performance of an intensified (ICCD) and
      nonintensified (CCD) detectors for detection of plasma emission in LIBS. The CCD
      is used in combination with a mechanical chopper, which blocks the early
      continuum radiation from the plasma. The detectors are attached sequentially to
      an echelle spectrometer under the same experimental conditions. The laser plasma
      is induced on a series of steel samples under atmospheric conditions. Our results
      indicate that there is no substantial difference in the performance of the CCD
      and ICCD. Signal-to-noise ratios and limits of detection achieved with the CCD
      for Si, Ni, Cr, Mo, Cu, and V in steel are comparable or even better than those
      obtained with the ICCD. This result is further confirmed by simulation of the
      plasma emission signal and the corresponding response of the detectors in the
      limit of quantum (photon) noise.

PMID- 17503766
TI  - Detection of heavy metal ions in water by high-resolution surface plasmon
      resonance spectroscopy combined with anodic stripping voltammetry.
AB  - High-resolution differential surface plasmon resonance (SPR) with anodic
      stripping voltammetry (ASV) capability has been demonstrated for detecting heavy
      metal ions in water. Metal ions are electroplated onto the gold SPR sensing
      surface and are quantitatively detected by stripping voltammetry. Both the SPR
      angular shift and electrochemical current signal are recorded to identify the
      type and amount of the metal ions in water. The performance of the combined
      approach is further enhanced by a differential detection approach. The gold
      sensor surface is divided into a reference and a sensing area, and the difference
      in the SPR angles from the two areas is detected with a quadrant cell
      photodetector as a differential signal. Our system demonstrated quantitative
      detection of copper, lead, and mercury ions in water from part-per-million to sub
      part-per-billion levels with good linearity.

PMID- 17503767
TI  - Wood cellulose preparation methods and mass spectrometric analyses of delta13C,
      delta18O, and nonexchangeable delta2H values in cellulose, sugar, and starch: an
      interlaboratory comparison.
AB  - Interlaboratory comparisons involving nine European stable isotope laboratories
      have shown that the routine methods of cellulose preparation resulted in data
      that generally agreed within the precision of the isotope ratio mass spectrometry
      (IRMS) method used: +/-0.2 per thousand for carbon and +/-0.3 per thousand for
      oxygen. For carbon, the results suggest that holocellulose is enriched up to 0.39
      per thousand in 13C relative to the purified alpha-cellulose. The comparisons of
      IRMS measurements of carbon on cellulose, sugars, and starches showed low
      deviations from -0.23 to +0.23 per thousand between laboratories. For oxygen,
      IRMS measurements varied between means from -0.39 to 0.58 per thousand, -0.89 to
      0.42 per thousand, and -1.30 to 1.16 per thousand for celluloses, sugars, and
      starches, respectively. This can be explained by different effects arising from
      the use of low- or high-temperature pyrolysis and by the variation between
      laboratories in the procedures used for drying and storage of samples. The
      results of analyses of nonexchangeable hydrogen are very similar in means with
      standard deviations between individual methods from +/-2.7 to +/-4.9 per
      thousand. The use of a one-point calibration (IAEA-CH7) gave significant positive
      offsets in delta2H values up to 6 per thousand. Detailed analysis of the results
      allows us to make the following recommendations in order to increase quality and
      compatibility of the common data bank: (1) removal of a pretreatment with organic
      solvents, (2) a purification step with 17% sodium hydroxide solution during
      cellulose preparation procedure, (3) measurements of oxygen isotopes under an
      argon hood, (4) use of calibration standard materials, which are of similar
      nature to that of the measured samples, and (5) using a two-point calibration
      method for reliable result calculation.

PMID- 17503768
TI  - Sputtering yields for C60 and Au3 bombardment of water ice as a function of
      incident kinetic energy.
AB  - The total sputtering yields for water ice due to kiloelectronvolt cluster
      bombardment have been measured and compared to the predictions made by the
      mesoscale energy deposition footprint (MEDF) model. For C60 bombardment, the
      experimental yield varies almost linearly from 820 water molecule equivalents at
      an incident kinetic energy of 10 keV to 10 100 water molecule equivalents at a
      kinetic energy of 120 keV. For Au3 bombardment, the experimental yield varies
      almost linearly from 630 water molecule equivalents at an incident energy of 10
      keV and rises to 1200 water molecule equivalents at 25 keV. The MEDF model is
      used to calculate relative yield trends with respect to incident energy using
      short-time molecular dynamics simulations. The results of these calculations
      indicate that the model can effectively predict the yield trends observed for
      these two clusters in experiments, although there is a consistent overestimate of
      the predicted induced C60 yield. It is hypothesized that this overestimate can be
      explained by the absence of reactions and ionization processes in the current
      simulations. Despite this omission, experimental yield trends can be accurately
      predicted using relatively small amounts of computer time. The success of the
      model in predicting the yield of water from ice films using a variety of energies
      and projectiles suggests this approach may greatly aid in the optimization of
      experimental configurations.

PMID- 17503769
TI  - Surface-enhanced Raman spectroscopy of soft-landed polyatomic ions and molecules.
AB  - Surface-enhanced Raman spectroscopy (SERS) was used to detect and characterize
      polyatomic cations and molecules that were electrosprayed into the gas phase and
      soft-landed in vacuum on plasma-treated silver substrates. Organic dyes such as
      crystal violet and Rhodamine B, the nucleobase cytosine, and nucleosides cytidine
      and 2'-deoxycytidine were immobilized by soft landing on plasma-treated metal
      surfaces at kinetic energies ranging from near thermal to 200 eV. While enhancing
      Raman scattering 10(5)-10(6)-fold, the metal surface effectively quenches the
      fluorescence that does not interfere with the Raman spectra. SERS spectra from
      submonolayer amounts of soft-landed compounds were sufficiently intense and
      reproducible to allow identification of Raman active vibrational modes for
      structure assignment. Soft-landed species appear to be microsolvated on the
      surface and bound via ion pairing or pi-complexation to the Ag atoms and ions in
      the surface oxide layer. Comparison of spectra from soft-landed and solution
      samples indicates that the molecules survive soft landing without significant
      chemical damage even when they strike the surface at hyperthermal collision
      energies.

PMID- 17503770
TI  - Fluorescence correlation spectroscopy assay for gliadin in food.
AB  - Gliadin proteins are primarily responsible for celiac disease. As gliadin is a
      complex mixture of proteins difficult to solubilize and to extract from food, it
      is difficult to develop an assay capable of accurate quantization of gliadin in
      food for celiac patients. In this work, we present an advanced fluorescence assay
      for the detection of traces of gliadin in food. The described assay is based on
      measurement of the fluctuations of fluorescein-labeled gliadin peptides (GP) in a
      focused laser beam in the absence and in the presence of anti-GP antibodies. A
      competitive assay based on the utilization of unlabeled GP was developed. The
      obtained results indicate that the combination of high-avidity IgG antibodies
      together with the innovative fluorescence immunoassay strategy resulted in a
      gluten detection limit of 0.006 ppm, which it is much lower than the values
      reported in the literature.

PMID- 17503772
TI  - Oxidation of 4-methylcatechol: implications for the oxidation of catecholamines.
AB  - At alkaline pH, 4-methylcatechol oxidizes more rapidly than the related
      catecholamines: dopamine, norepinephrine, and epinephrine. This oxidation is not
      inhibited by superoxide dismutase or catalase, indicating that O2 itself is the
      oxidant, but the reduction potential of O2/O2-* is too low for it to oxidize 4
      methylcatechol directly. Instead, O2 oxidizes the 4-methylcatechol semiquinone,
      which is formed by comproportionation of 4-methylcatechol and its o-quinone.
      Aniline reacts very quickly with the o-quinone and thus stops the
      comproportionation reaction that oxidizes 4-methylcatechol to the semiquinone.
      Oxidation of 4-methylcatechol then requires superoxide, and in the presence of
      aniline, oxidation of 4-methylcatechol by O2 is inhibited by superoxide
      dismutase. When catecholamines oxidize, the side chain amine inserts into the
      catechol o-quinone, forming a bicyclic compound. By eliminating the quinone, this
      ring closure prevents comproportionation and the consequent oxidation of
      catecholamines by O2. It also prevents reaction of the quinone with other
      compounds and the formation of potentially toxic products.

PMID- 17503773
TI  - Assembly and signaling of CRLR and RAMP1 complexes assessed by BRET.
AB  - Biochemical and functional evidence suggest that the calcitonin receptor-like
      receptor (CRLR) interacts with receptor activity-modifying protein-1 (RAMP1) to
      generate a calcitonin gene-related peptide (CGRP) receptor. Using bioluminescence
      resonance energy transfer (BRET), we investigated the oligomeric assembly of the
      CRLR-RAMP1 signaling complex in living cells. As for their wild-type
      counterparts, fusion proteins linking CRLR and RAMP1 to the energy donor Renilla
      luciferase (Rluc) and energy acceptor green fluorescent protein (GFP) reach the
      cell surface only upon coexpression of CRLR and RAMP1. Radioligand binding and
      cAMP production assays also confirmed that the fusion proteins retained normal
      functional properties. BRET titration experiments revealed that CRLR and RAMP1
      associate selectively to form heterodimers. This association was preserved for a
      mutated RAMP1 that cannot reach the cell surface, even in the presence of CRLR,
      indicating that the deficient targeting resulted from the altered conformation of
      the complex rather than a lack of heterodimerization. BRET analysis also showed
      that, in addition to associate with one another, both CRLR and RAMP1 can form
      homodimers. The homodimerization of the coreceptor was further confirmed by the
      ability of RAMP1 to prevent cell surface targeting of a truncated RAMP1 that
      normally exhibits receptor-independent plasma membrane delivery. Although the
      role of such dimerization remains unknown, BRET experiments clearly demonstrated
      that CRLR can engage signaling partners, such as G proteins and beta-arrestin,
      following CGRP stimulation, only in the presence of RAMP1. In addition to shed
      new light on the CRLR-RAMP1 signaling complex, the BRET assays developed herein
      offer new biosensors for probing CGRP receptor activity.

PMID- 17503774
TI  - Polarized fluorescence of aggregated bacteriochlorophyll c and baseplate
      bacteriochlorophyll a in single chlorosomes isolated from Chloroflexus
      aurantiacus.
AB  - The polarization anisotropy of fluorescence from single chlorosomes isolated from
      a green filamentous bacterium, Chloroflexus aurantiacus, was measured using a
      confocal laser microscope at 13 K. Each single chlorosome that is floating in a
      frozen solvent exhibited strong polarization anisotropy of fluorescence. We
      calculated the degrees of fluorescence polarization for 51 floating single
      chlorosomes. The value ranged from 0.1 to 0.76 for the BChl-c aggregate in the
      core chlorosomes and from 0 to 0.4 for the energy acceptor BChl-a in the
      baseplate protein in the outer membrane. The shifts in polarization angles
      between the two emission bands were distributed over all the possible values with
      a sharp peak around 90 degrees , suggesting the perpendicular orientation between
      the transition dipoles of the fluorescence emission from the BChl-c aggregate and
      that from BChl-a. A simulation assuming a random orientation of chlorosomes
      reproduced the experimental results exactly. The analysis further indicated the
      appreciable contribution of the transition dipole of BChl-c that has an
      orientation perpendicular to the major polarization axis in each chlorosome.
      Small values of the degrees of polarization implied the BChl-a transition dipole
      to be somewhat tilted with respect to the normal of the cytoplasmic membrane to
      which chlorosomes are attached. These conclusions can be obtained only by
      observing the fluorescence of single chlorosomes.

PMID- 17503775
TI  - SelT, SelW, SelH, and Rdx12: genomics and molecular insights into the functions
      of selenoproteins of a novel thioredoxin-like family.
AB  - Selenium is an essential trace element in many life forms due to its occurrence
      as a selenocysteine (Sec) residue in selenoproteins. The majority of mammalian
      selenoproteins, however, have no known function. Herein, we performed extensive
      sequence similarity searches to define and characterize a new protein family,
      designated Rdx, that includes mammalian selenoproteins SelW, SelV, SelT and SelH,
      bacterial SelW-like proteins and cysteine-containing proteins of unknown function
      in all three domains of life. An additional member of this family is a mammalian
      cysteine-containing protein, designated Rdx12, and its fish selenoprotein
      orthologue. Rdx proteins are proposed to possess a thioredoxin-like fold and a
      conserved CxxC or CxxU (U is Sec) motif, suggesting a redox function. We cloned
      and characterized three mammalian members of this family, which showed distinct
      expression patterns in mouse tissues and different localization patterns in cells
      transfected with the corresponding GFP fusion proteins. By analogy to
      thioredoxin, Rdx proteins can use catalytic cysteine (or Sec) to form transient
      mixed disulfides with substrate proteins. We employed this property to identify
      cellular targets of Rdx proteins using affinity columns containing mutant
      versions of these proteins. Rdx12 was found to interact with glutathione
      peroxidase 1, whereas 14-3-3 protein was identified as one of the targets of
      mammalian SelW, suggesting a mechanism for redox regulation of the 14-3-3 family
      of proteins.

PMID- 17503776
TI  - 5'-Peroxyadenosine and 5'-peroxyadenosylcobalamin as intermediates in the aerobic
      photolysis of adenosylcobalamin.
AB  - The photolysis of adenosylcobalamin (coenzyme B12) results in homolytic cleavage
      of the Co-C5' bond, forming cob(II)alamin and the 5'-deoxyadenosyl radical. In
      the presence of molecular oxygen, it has been proposed that the primary reaction
      is interception of the 5'-deoxyadenosyl radical by O2 to form adenosine-5'
      aldehyde as the product (Hogenkamp, H. P. C., Ladd, J. N., and Barker, H. A.
      (1962) J. Biol. Chem. 237, 1950-1952). 5'-Peroxyadenosine is here found to be the
      initial nucleoside product of this reaction and found to decompose to adenosine
      5'-aldehyde. Evidence indicates that 5'-peroxyadenosine arises from the
      hydrolysis of 5'-peroxyadenosylcobalamin, with the formation of cob(III)alamin.
      5'-Peroxyadenosine undergoes further decomposition to adenosine-5'-aldehyde as
      the major final product of aerobic photolysis as well as to adenosine and adenine
      as minor products. In a cobalamin-dependent process, 5'-peroxyadenosine becomes
      re-ligated to cob(III)alamin to form 5'-peroxyadenosylcobalamin, which quickly
      decomposes to adenosine-5'-aldehyde and cob(III)alamin. This is supported by
      spectrophotometric observations of both rapidly photolyzed adenosylcobalamin and
      the reaction of cob(III)alamin with excess 5'-peroxyadenosine. 5'-Peroxyadenosine
      also slowly undergoes cobalamin-independent decomposition to adenosine-5'
      aldehyde and the minor products adenosine and adenine. The present study provides
      a detailed description of the products initially formed when aqueous,
      homolytically cleaved adenosylcobalamin reacts with molecular oxygen and provides
      a detailed description of the behavior of those products subsequent to
      photolysis.

PMID- 17503777
TI  - A conserved cis-proline precludes metal binding by the active site thiolates in
      members of the thioredoxin family of proteins.
AB  - Many thioredoxin-fold proteins possess a conserved cis-proline located in their C
      terminal portions. This residue, as well as catalytic and resolving cysteines, is
      a key functional group in the active sites of these thiol-disulfide
      oxidoreductases. However, the specific function of the proline is poorly
      understood, and some thioredoxin-fold proteins lack this residue. Herein, we
      found that mutation of a cis-proline, Pro75, in human thioredoxin to serine,
      threonine, or alanine leads to the formation of an Fe2-S2 cluster in this
      protein. Further mutagenesis studies revealed that the first cysteine in the CxxC
      motif and a cysteine in the C-terminal region of the protein were responsible for
      metal binding. Replacement of Pro75 with arginine, a residue that occurs in place
      of Pro in peroxiredoxins, also led to the formation of the cluster in the
      thioredoxin. In addition, we found that mutation of the TxxC active site in a
      peroxiredoxin to the CxxC form could lead to coordination of an Fe2-S2 cluster in
      these proteins in vitro. Sco1, a distantly related thioredoxin-fold protein, has
      histidine in place of the cis-proline, and this residue binds copper. The
      Pro75His mutation led to increased copper binding by human thioredoxin when cells
      were grown in the presence of this trace element. Taken together, our data
      suggest that an important function of Pro75 in human thioredoxin, and likely
      other members of this superfamily, is to prevent metal binding by the reactive
      thiolate-based active site.

PMID- 17503778
TI  - Structural modeling of sequence specificity by an autoantibody against single
      stranded DNA.
AB  - 11F8 is a sequence-specific pathogenic anti-single-stranded (ss)DNA autoantibody
      isolated from a lupus prone mouse. Site-directed mutagenesis of 11F8 has shown
      that six binding site residues (R31VH, W33VH, L97VH, R98VH, Y100VH, and Y32VL)
      contribute 80% of the free energy for complex formation. Mutagenesis results
      along with intermolecular distances obtained from fluorescence resonance energy
      transfer were implemented here as restraints to model docking between 11F8 and
      the sequence-specific ssDNA. The model of the complex suggests that aromatic
      stacking and two sets of bidentate hydrogen bonds between binding site arginine
      residues (R31VH and R96VH) and loop nucleotides provide the molecular basis for
      high affinity and specificity. In part, 11F8 utilizes the same ssDNA binding
      motif of Y32VL, H91VL, and an aromatic residue in the third complementarity
      determining region to recognize thymine-rich sequences as do two anti-ssDNA
      autoantibodies crystallized in complex with thymine. R31SVH is a dominant somatic
      mutation found in the J558 germline sequence that is implicated in 11F8 sequence
      specificity. A model of the mutant R31S11F8.ssDNA complex suggests that different
      interface contacts occur when serine replaces arginine 31 at the binding site.
      The modeled contacts between the R31S11F8 mutant and thymine are closely related
      to those observed in other anti-ssDNA binding antibodies, while we find
      additional contacts between 11F8 and ssDNA that involve amino acids not utilized
      by the other antibodies. These data-driven 11F8.ssDNA models provide testable
      hypotheses concerning interactions that mediate sequence specificity in 11F8 and
      the effects of somatic mutation on ssDNA recognition.

PMID- 17503779
TI  - Biologic functions of the G12 subfamily of heterotrimeric g proteins: growth,
      migration, and metastasis.
AB  - The G12 subfamily of heterotrimeric G proteins has been the subject of intense
      scientific interest for more than 15 years. During this period, studies have
      revealed more than 20 potential G12-interacting proteins and numerous signaling
      axes emanating from the G12 proteins, Galpha12 and Galpha13. In addition, more
      recent studies have begun to illuminate the various and sundry functions that the
      G12 subfamily plays in biology. In this review, we summarize the diverse range of
      proteins that have been identified as Galpha12 and/or Galpha13 interactors and
      describe ongoing studies designed to dissect the biological roles of specific
      Galpha-effector protein interactions. Further, we describe and discuss the
      expanding role of G12 proteins in the biology of cells, focusing on the distinct
      properties of this subfamily in regulating cell proliferation, cell migration,
      and metastatic invasion.

PMID- 17503780
TI  - Lipid interaction converts prion protein to a PrPSc-like proteinase K-resistant
      conformation under physiological conditions.
AB  - The conversion of prion protein (PrP) to the pathogenic PrPSc conformation is
      central to prion disease. Previous studies revealed that PrP interacts with
      lipids and the interaction induces PrP conformational changes, yet it remains
      unclear whether in the absence of any denaturing treatment, PrP-lipid interaction
      is sufficient to convert PrP to the classic proteinase K-resistant conformation.
      Using recombinant mouse PrP, we analyzed PrP-lipid interaction under
      physiological conditions and followed lipid-induced PrP conformational change
      with proteinase K (PK) digestion. We found that the PrP-lipid interaction was
      initiated by electrostatic contact and followed by hydrophobic interaction. The
      PrP-lipid interaction converted full-length alpha-helix-rich recombinant PrP to
      different forms. A significant portion of PrP gained a conformation reminiscent
      of PrPSc, with a PrPSc-like PK-resistant core and increased beta-sheet content.
      The efficiency for lipid-induced PrP conversion depended on lipid headgroup
      structure and/or the arrangement of lipids on the surface of vesicles. When lipid
      vesicles were disrupted by Triton X-100, PrP aggregation was necessary to
      maintain the lipid-induced PrPSc-like conformation. However, the PK resistance of
      lipid-induced PrPSc-like conformation does not depend on amyloid fiber formation.
      Our results clearly revealed that the lipid interaction can overcome the energy
      barrier and convert full-length alpha-helix-rich PrP to a PrPSc-like conformation
      under physiological conditions, supporting the relevance of lipid-induced PrP
      conformational change to in vivo PrP conversion.

PMID- 17503781
TI  - Hydration and temperature similarly affect light-induced protein structural
      changes in the chromophoric domain of phototropin.
AB  - Phototropin is a blue-light sensor protein in plants, and LOV domain binds a
      flavin mononucleotide (FMN) as a chromophore. A photointermediate state, S390, is
      formed by light-induced adduct formation between FMN and an S-H group of nearby
      cysteine, which triggers protein structural changes for kinase activation in
      phototropin. We previously studied the low-temperature Fourier transform infrared
      (FTIR) spectra between the S390 and unphotolyzed states for a LOV2 domain of a
      phototropin from Adiantum (neo1-LOV2), and found that the protein structures of
      the S390 intermediate are highly temperature dependent (Iwata, T., Nozaki, D.,
      Tokutomi, S., Kagawa, T., Wada, M., and Kandori, H. (2003) Biochemistry 42, 8183
      8191). At physiological temperature, amide-I vibration at 1640-1620 cm-1 is
      significantly changed, implying structural alteration of beta-sheet region. Such
      changes are largely suppressed at low temperatures, though S390 is formed. This
      observation suggested the presence of progressive protein structural changes in
      the unique active state (S390). Here we report that the hydration dependence of
      the amide-I vibrational bands in neo1-LOV2 is similar to the temperature
      dependence. As hydration of the sample is lowered, amide-I vibration at 1640-1620
      cm-1 is significantly reduced. Instead, amide-I vibration at 1694 cm-1 newly
      emerged at low hydration as well as at low temperature, which shows a weakened
      hydrogen bond in the loop region. Spectral coincidence between low hydrations and
      temperatures strongly suggested that protein structural changes are similarly
      restricted under such conditions. It is likely that protein fluctuations are
      prerequisite for formation of the active state of neo1-LOV2.

PMID- 17503782
TI  - Recruitment of both uniform and differential binding energy in enzymatic
      catalysis: xylanases from families 10 and 11.
AB  - The contributions of enzyme-substrate hydrogen-binding interactions to catalysis
      by two different families of xylanases were evaluated through kinetic studies
      with two representative wild-type enzymes, Cellulomonas fimi xylanase (Cex) and
      Bacillus circulans xylanase (Bcx), on a series of monodeoxygenated and
      monodeoxyfluorinated p-nitrophenyl xylobioside substrates. Effects of
      substitution in the distal (-2 subsite) sugar on kcat/Km for Cex were moderately
      large (up to 2.9 kcal mol-1), with no effect seen on kcat. By contrast,
      substantial effects upon both kcat and kcat/Km were seen for substrates modified
      in the proximal (-1 subsite) sugar. Very similar results were obtained with Bcx.
      Kinetic analyses with a series of eight mutants of Cex in which active site
      residues interacting with the substrate were mutated yielded complementary
      insights. Again, interactions with the distal (-2) sugar were seen to contribute
      substantially to kcat/Km (up to 3.7 kcal mol-1), thus to the formation of the
      glycosyl-enzyme intermediate, but not to kcat, thus to the hydrolysis of the
      glycosyl-enzyme. Interactions with the proximal (-1) sugar are much more
      significant, contributing up to 6.7 kcal mol-1 to both kcat/Km and kcat. These
      results together indicate that interactions with the distal sugar maintain
      similar magnitudes in the transition states for glycosylation and deglycosylation
      as well as in the glycosyl-enzyme intermediate and can be referred to as "uniform
      binding interactions" in the parlance of Albery and Knowles (Albery, W. J., and
      Knowles, J. R. (1976) Biochemistry 15, 5631-5640). Interactions with the proximal
      sugar are considerably stronger at the deglycosylation transition state than in
      the intermediate, and fall into the category of differential binding
      interactions. This behavior likely has its origins in the changes in ring
      conformation of the proximal sugar but not of the distal sugar between the ground
      state and the reaction transition state. Correlation of these individual
      interaction energies with the hydrogen-bonding pattern seen in the glycosyl
      enzyme intermediate allows for the assignment of hydrogen-bond strengths to each
      interaction, with good correlation between the two approaches. These findings are
      relevant to the discussion of remote binding effects upon enzymatic catalysis.

PMID- 17503783
TI  - Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in
      tumor growth and angiogenesis.
AB  - Mammalian hyaluronidases hydrolyze hyaluronan, a polysaccharide of diverse
      physiological roles found in all tissues and body fluids. In addition to its
      function in normal cellular hyaluronan turnover, human hyaluronidase-1 is
      implicated in cancer proliferation, angiogenesis, and inflammatory diseases; its
      expression is up-regulated in advanced stages of bladder cancer, whereas the
      expression of the alternative splice-variants is down-regulated. The crystal
      structure reveals a molecule composed of two closely associated domains: a
      catalytic domain that adopts a distorted (beta/alpha)8 barrel resembling that of
      bee venom hyaluronidase, and a novel, EGF-like domain, characteristic of
      involvement in protein-protein interactions and regulatory processes. The
      structure shows that the fold of this unique EGF-like domain is intact in four
      alternative splice-variants, whereas the catalytic domain is likely to be
      unfolded. Thus, these variants may function by competing with the full-length
      enzyme for the putative protein partner and regulating enzymatic activity in
      healthy cells.

PMID- 17503784
TI  - PKCepsilon increases phosphorylation of the cardiac myosin binding protein C at
      serine 302 both in vitro and in vivo.
AB  - Cardiac myosin binding protein C (cMyBPC) phosphorylation is essential for normal
      cardiac function. Although PKC was reported to phosphorylate cMyBPC in vitro, the
      relevant PKC isoforms and functions of PKC-mediated cMyBPC phosphorylation are
      unknown. We recently reported that a transgenic mouse model with cardiac-specific
      overexpression of PKCepsilon (PKCepsilon TG) displayed enhanced sarcomeric
      protein phosphorylation and dilated cardiomyopathy. In the present study, we have
      investigated cMyBPC phosphorylation in PKCepsilon TG mice. Western blotting and
      two-dimensional gel electrophoresis demonstrated a significant increase in cMyBPC
      serine (Ser) phosphorylation in 12-month-old TG mice compared to wild type (WT).
      In vitro PKCepsilon treatment of myofibrils increased the level of cMyBPC Ser
      phosphorylation in WT mice to that in TG mice, whereas treatment of TG myofibrils
      with PKCepsilon showed only a minimal increase in cMyBPC Ser phosphorylation.
      Three peptide motifs of cMyBPC were identified as the potential PKCepsilon
      consensus sites including a 100% matched motif at Ser302 and two nearly matched
      motifs at Ser811 and Ser1203. We treated synthetic peptides corresponding to the
      sequences of these three motifs with PKCepsilon and determined phosphorylation by
      mass spectrometry and ELISA assay. PKCepsilon induced phosphorylation at the
      Ser302 site but not at the Ser811 or Ser1203 sites. A S302A point mutation in the
      Ser302 peptide abolished the PKCepsilon-dependent phosphorylation. Taken
      together, our data show that the Ser302 on mouse cMyBPC is a likely PKCepsilon
      phosphorylation site both in vivo and in vitro and may contribute to the dilated
      cardiomyopathy associated with increased PKCepsilon activity.

PMID- 17503785
TI  - Stability for function trade-offs in the enolase superfamily "catalytic module".
AB  - Enzyme catalysis reflects a dynamic interplay between charged and polar active
      site residues that facilitate function, stabilize transition states, and maintain
      overall protein stability. Previous studies show that substituting neutral for
      charged residues in the active site often significantly stabilizes a protein,
      suggesting a stability trade-off for functionality. In the enolase superfamily, a
      set of conserved active site residues (the "catalytic module") has repeatedly
      been used in nature in the evolution of many different enzymes for the
      performance of unique overall reactions involving a chemically diverse set of
      substrates. This catalytic module provides a robust solution for catalysis that
      delivers the common underlying partial reaction that supports all of the
      different overall chemical reactions of the superfamily. As this module has been
      so broadly conserved in the evolution of new functions, we sought to investigate
      the extent to which it follows the stability-function trade-off. Alanine
      substitutions were made for individual residues, groups of residues, and the
      entire catalytic module of o-succinylbenzoate synthase (OSBS), a member of the
      enolase superfamily from Escherichia coli. Of six individual residue
      substitutions, four (K131A, D161A, E190A, and D213A) substantially increased
      protein stability (by 0.46-4.23 kcal/mol), broadly consistent with prediction of
      a stability-activity trade-off. The residue most conserved across the
      superfamily, E190, is by far the most destabilizing. When the individual
      substitutions were combined into groups (as they are structurally and
      functionally organized), nonadditive stability effects emerged, supporting
      previous observations that residues within the module interact as two functional
      groups within a larger catalytic system. Thus, whereas the multiple-mutant
      enzymes D161A/E190A/D213A and K131A/K133A/D161A/E190A/D213A/K235A (termed 3KDED)
      are stabilized relative to the wild-type enzyme (by 1.77 and 3.68 kcal/mol,
      respectively), the net stabilization achieved in both cases is much weaker than
      what would be predicted if their stability contributions were additive.
      Organization of the catalytic module into systems that mitigate the expected
      stability cost due to the presence of highly charged active site residues may
      help to explain its repeated use for the evolution of many different functions.

PMID- 17503786
TI  - Parallel solution-phase synthesis of 4H-benzo[1,4]thiazin-3-one and 1,1-dioxo-1,4
      dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one derivatives from 1,5-difluoro-2,4
      dinitrobenzene.
AB  - This paper discusses the synthesis of privileged structures 4H-benzo[1,4]thiazin
      3-one and 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one derivatives
      in a parallel solution-phase manner using 1,5-difluoro-2,4-dinitrobenzene. Each
      scaffold possesses four diversity points. A cheap and efficient oxidant, urea
      hydrogen peroxide (UHP), was applied for the introduction of the sulfone group.
      The intramolecular cyclization to 1,1-dioxo-1,4-dihydro-2H-1lambda6
      benzo[1,4]thiazin-3-one was achieved by microwave assistance or the use of an
      inorganic base.

PMID- 17503787
TI  - Quantum chemical study of the mechanism of action of vitamin K carboxylase (VKC).
      IV. Intermediates and transition states.
AB  - We studied proposed steps for the enzymatic formation of gamma-carboxyglutamic
      acid by density functional theory (DFT) quantum chemistry. Our results for one
      potentially feasible mechanism show that a vitamin K alkoxide intermediate can
      abstract a proton from glutamic acid at the gamma-carbon to form a carbanion and
      vitamin K epoxide. The hydrated carbanion can then react with CO2 to form gamma
      carboxyglutamic acid. Computations at the B3LYP/6-311G** level were used to
      determine the intermediates and transition states for the overall process. The
      activation free energy for the gas-phase path is 22 kcal/mol, with the rate
      limiting step for the reaction being the attack of the carbanion on CO2.
      Additional solvation studies, however, indicate that the formation of the
      carbanion step can be competitive with the CO2 attack step in high-dielectric
      systems. We relate these computations to the entire vitamin K cycle in the blood
      coagulation cascade, which is essential for viability of vertebrates.

PMID- 17503788
TI  - Chemistry in acetone complexes of metal dications: a remarkable ethylene
      production pathway.
AB  - Electrospray ionization can generate microsolvated multiply charged metal ions
      for various metals and ligands, allowing exploration of chemistry within such
      clusters. The finite size of these systems permits comparing experimental results
      with accurate calculations, creating a natural laboratory to research ion
      solvation. Mass spectrometry has provided much insight into the stability and
      dissociation of ligated metal cations. While solvated singly charged ions tend to
      shrink by ligand evaporation, solvated polycations below a certain size exhibit
      charge reduction and/or ligand fragmentation due to organometallic reactions.
      Here we investigate the acetone complexes of representative divalent metals (Ca,
      Mn, Co, Ni, and Cu), comparing the results of collision-induced dissociation with
      the predictions of density functional theory. As for other solvated dications,
      channels involving proton or electron transfer compete with ligand loss and
      become dominant for smaller complexes. The heterolytic C-C bond cleavage is
      common, like in DMSO and acetonitrile complexes. Of primary interest is the
      unanticipated neutral ethylene loss, found for all metals studied except Cu and
      particularly intense for Ca and Mn. We focus on understanding that process in the
      context of competing dissociation pathways, as a function of metal identity and
      number of ligands. According to first-principles modeling, ethylene elimination
      proceeds along a complex path involving two intermediates. These results suggest
      that chemistry in microsolvated multiply charged ions may still hold major
      surprises.

PMID- 17503789
TI  - Reflected shock tube and theoretical studies of high-temperature rate constants
      for OH+CF3H<-->CF3+H2O and CF3+OH-->products.
AB  - The reflected shock tube technique with multipass absorption spectrometric
      detection of OH radicals at 308 nm, using either 36 or 60 optical passes
      corresponding to total path lengths of 3.25 or 5.25 m, respectively, has been
      used to study the bimolecular reactions, OH+CF3H-->CF3+H2O (1) and CF3+H2O-
      >OH+CF3H (-1), between 995 and 1663 K. During the course of the study, estimates
      of rate constants for CF3+OH-->products (2) could also be determined. Experiments
      on reaction -1 were transformed through equilibrium constants to k1, giving the
      Arrhenius expression k1=(9.7+/-2.1)x10(-12) exp(-4398+/-275K/T) cm3 molecule(-1)
      s(-1). Over the temperature range, 1318-1663 K, the results for reaction 2 were
      constant at k2=(1.5+/-0.4)x10(-11) cm3 molecule(-1) s(-1). Reactions 1 and -1
      were also studied with variational transition state theory (VTST) employing
      QCISD(T) properties for the transition state. These a priori VTST predictions
      were in good agreement with the present experimental results but were too low at
      the lower temperatures of earlier experiments, suggesting that either the barrier
      height was overestimated by about 1.3 kcal/mol or that the effect of tunneling
      was greatly underestimated. The present experimental results have been combined
      with the most accurate earlier studies to derive an evaluation over the extended
      temperature range of 252-1663 K. The three parameter expression k1=2.08x10(-17)
      T1.5513 exp(-1848 K/T) cm3 molecule(-1) s(-1) describes the rate behavior over
      this temperature range. Alternatively, the expression k1,th=1.78x10(-23) T3.406
      exp(-837 K/T) cm3 molecule(-1) s(-1) obtained from empirically adjusted VTST
      calculations over the 250-2250 K range agrees with the experimental evaluation to
      within a factor of 1.6. Reaction 2 was also studied with direct CASPT2 variable
      reaction coordinate transition state theory. The resulting predictions for the
      capture rate are found to be in good agreement with the mean of the experimental
      results and can be represented by the expression k2,th=2.42x10(-11) T-0.0650
      exp(134 K/T) cm3 molecule(-1) s(-1) over the 200-2500 K temperature range. The
      products of this reaction are predicted to be CF2O+HF.

PMID- 17503790
TI  - Hole-burning spectra of phenol-Arn (n = 1, 2) clusters: resolution of the isomer
      issue.
AB  - The hole-burning (HB) spectra of phenol-Arn (PhOH-Arn) clusters with n = 1 and 2
      have been measured in a molecular beam to clarify the possible existence of
      isomers. Two species were identified to give rise to signals in the S1-S0
      spectrum recorded for the n = 1 cluster; however, one of the species was found to
      originate from dissociation of an n = 2 cluster. Similarly, three species were
      observed in the spectrum of the n = 2 cluster, and two of them were assigned to n
      = 3 and larger clusters. The spectral contamination from larger size clusters was
      quantitatively explained by the dissociation after photoexcitation. The analysis
      of the spectra demonstrates that only a single isomer exists in the molecular
      beam for both the n = 1 and the n = 2 clusters. In addition to two previously
      detected intermolecular modes, a third low-frequency mode, assigned to an
      intermolecular bending vibration, is observed for the first time in the HB
      spectrum of the n = 2 cluster. The assignments of the intermolecular vibrations
      were confirmed by ab initio MO calculations. The observation of the third
      intermolecular vibration suggests that the geometry of the n = 2 cluster has Cs
      or lower symmetry.

PMID- 17503791
TI  - Thermodynamics and kinetics of methylboroxine.amine adduct formation: a
      computational study.
AB  - Density functional theory (B3LYP//6-311+G*) calculations including Poisson
      Boltzmann implicit solvent were applied to study the formation of the
      trimethylboroxine.amine adduct with respect to methylboronic acid monomers and
      free amine in solution. Potential intermediates and transition states between
      intermediates were calculated to assess the thermodynamic and kinetic factors
      controlling this transformation. Our calculations suggest that the rate
      determining steps are condensation reactions to form dimers and trimers, and
      closure of the boroxine ring. Fast amine exchange is expected throughout the
      transformation, and the most-stable intermediate is a dimer.amine adduct. Using
      our calculated barriers for the methyl system as a template, we assess the
      conversion of phenylboronic acid to the triphenylboroxine.amine adduct and find
      that the pathway is most likely similar, except that the transformation is
      thermodynamically and kinetically more favored for the phenyl system in the
      presence of pyridine.

PMID- 17503792
TI  - Stability of the hydrogen trioxy radical via infrared action spectroscopy.
AB  - The hydrogen trioxy radical (HO3) has been proposed as an intermediate in several
      important chemical reactions and relaxation processes involving OH in the
      atmosphere. In this work, the gas-phase infrared action spectrum of HO3 is
      obtained in the OH overtone region, along with the product state distribution of
      the OH fragment following dissociation. The highest observed OH product channel
      sets an upper limit for the HO-O2 binding energy of 6.12 kcal mol(-1). The
      experimental stability of HO3 and derived equilibrium constant imply that up to
      66% of atmospheric OH may be converted into HO3 in the tropopause region.

PMID- 17503794
TI  - Proteome analysis suggests that mitochondrial dysfunction in stressed endothelial
      cells is reversed by a soy extract and isolated isoflavones.
AB  - Apoptosis is a driving force in atherosclerosis development. A soy extract or a
      combination of the soy isoflavones genistein and daidzein inhibited apoptosis
      induced by oxidized LDL in endothelial cells. Proteome analysis revealed that the
      LDL-induced alterations of numerous proteins were reversed by the extract and the
      genistein/daidzein mixture but only three protein entities, all functionally
      linked to mitochondrial dysfunction, were regulated in common by both treatments.

PMID- 17503795
TI  - Enhanced a1 fragmentation for dimethylated proteins and its applications for N
      terminal identification and comparative protein quantitation.
AB  - In this work, dimethyl labeling at the protein level was developed to assist the
      fragmentation of intact proteins using the Q-TOF instrument. It was shown that a1
      ions were favorably enhanced upon collision-induced dissociation for dimethylated
      proteins with molecular mass below 20 kDa and without N-terminal modifications.
      This method is helpful in confirming proteolytic sites located at the N-terminus
      of proteins. Moreover, this labeling could be incorporated with stable isotopes
      for comparative profiling at the protein level, in which the heavily labeled and
      lightly labeled a1 ions were generated from the corresponding proteins upon high
      voltage collisions in a broad mass region that covered all of the charge states
      of the proteins. Using hemoglobin as an example, a linear dynamic range from 1:1
      to 1:20 was satisfactorily obtained with an R2 value greater than 0.99. This
      approach appears to be promising for top-down proteomics.

PMID- 17503797
TI  - Tyrosine polysulfation of human salivary histatin 1. A post-translational
      modification specific of the submandibular gland.
AB  - Histatin 1 (His-1) derivatives showing serial mass increases of 80.0 +/- 0.1 Da
      were detected in human saliva by HPLC-ESI-MS. The same derivatives were also
      found in granules of submandibular glands and secretions of
      submandibular/sublingual glands, but not in granules and secretions of parotid
      glands. Only one phosphate group was present in His-1 and its derivatives, since
      treatment with alkaline phosphatase provided an 80.0 Da mass decrease. His-1
      derivatives were almost completely transformed into His-1 by treatment with 1 M
      HCl at 100 degrees C, suggesting the presence of O-sulfotyrosine, which is more
      labile than phospho-Tyr to acidic hydrolysis. CE-MS analysis of pronase extensive
      digestion of derivatives confirmed the presence of sulfotyrosine. Derivatives
      were digested by trypsin, proteinase K, and protease V-8 and analyzed by
      different MS strategies. The results allowed locating sulfation on the last four
      tyrosines (Tyr 27, 30, 34, and 36). This study is the first report of the gland
      specific sulfation of a salivary phosphopeptide in vivo.

PMID- 17503796
TI  - Tumor Necrosis Factor-alpha- and interleukin-1-induced cellular responses:
      coupling proteomic and genomic information.
AB  - The pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNFalpha) and
      Interleukin-1 (IL-1) mediate the innate immune response. Dysregulation of the
      innate immune response contributes to the pathogenesis of cancer, arthritis, and
      congestive heart failure. TNFalpha- and IL-1-induced changes in gene expression
      are mediated by similar transcription factors; however, TNFalpha and IL-1
      receptor knock-out mice differ in their sensitivities to a known initiator
      (lipopolysaccharide, LPS) of the innate immune response. The contrasting
      responses to LPS indicate that TNFalpha and IL-1 regulate different processes. A
      large-scale proteomic analysis of TNFalpha- and IL-1-induced responses was
      undertaken to identify processes uniquely regulated by TNFalpha and IL-1. When
      combined with genomic studies, our results indicate that TNFalpha, but not IL-1,
      mediates cell cycle arrest.

PMID- 17503798
TI  - Relative specificities of water and ammonia losses from backbone fragments in
      collision-activated dissociation.
AB  - Analysis of a database containing over 20,000 high-resolution collision
      activation mass spectra of tryptic peptide dications was employed to study the
      relative specificity of neutral losses from backbone fragments. The high
      resolution of the FTMS instrument allowed for the first time the first isotope of
      the water loss and the monoisotope of the ammonia loss to be distinguished.
      Contrary to a popular belief, water losses from y' ions are not specific enough
      to rely upon for detecting the presence of amino acids with oxygen in the side
      chains. At the same time, ammonia loss from b ions is sufficiently specific
      (>95%) to detect the presence of amino acids Gln, Asn, His, Lys, and Arg. This
      feature will be useful for de novo algorithms for high-resolution MS data. Clear
      trends were observed when the effect of amino acids proximate to the cleavage
      site on the rate of loss formation was studied. These trends turned out to be
      different for losses from b and y ions.

PMID- 17503799
TI  - Comprehensive conformational analysis of the nucleoside analogue 2'-beta-deoxy-6
      azacytidine by DFT and MP2 calculations.
AB  - A comprehensive conformational analysis of isolated 2'-beta-deoxy-6-azacytidine
      (d6AC), an analogue of therapeutically active 6-azacytidine (6AC), has been
      performed by means of ab initio calculations at the MP2/6-311++G(2df,pd)//DFT
      B3LYP/6-31G(d,p) level of theory. Among the 81 conformers located within a 7.83
      kcal/mol Gibbs energy range at T = 298.15 K, 38 contain syn-oriented bases with
      respect to 2'-deoxyribose; the other conformers include anti-oriented bases.
      Energetic analysis of these conformers shows that conformational equilibrium of
      isolated d6AC at T = 298.15 K is shifted to syn conformation with a syn/anti
      ratio estimated as 61.4%:38.6%. As far as the sugar conformation is concerned, 40
      conformers contain north (N) (with 0.3 degrees < or = P < or = 40.1 degrees), and
      the rest possess south (S) (with 157.1 degrees < or = P < or = 207.0 degrees)
      puckers, where P is the pseudorotational angle of the furanose ring. The S/N
      occupancy ratio is estimated as 80.2%:19.8% (T = 298.15 K). The two most stable
      conformers are energetically quasidegenerate and correspond to both C2'-endo/syn
      conformers differing only by orientation of the O3'H hydroxyl group. They are
      both stabilized by means of similar intramolecular H-bonds, i.e., O5'H...O2,
      C2'H2...O2, and C2'H2...O5'. As examined by AIM criteria, from 1 to 3 H-bonds per
      conformer were identified among 13 possible interactions: O5'H...O2, O5'H...N6,
      O3'H...O5', O5'H...O3', C1'H...O2, C2'H2...O2, C2'H2...O5', C3'H...O2, C3'H...N6,
      C5'H1...O2, C5'H2...O2, C5'H1...N6, and C5'H2...N6. The biological effect of d6AC
      is conceived as an inhibition of replicative DNA polymerase caused by an unusual
      orientation of the sugar residue against the base in the only A form DNA-like
      conformer.

PMID- 17503800
TI  - Down to the quantum limit at the neutral-to-ionic phase transition of (BEDT-TTF)
      (ClMe-TCNQ): symmetry analysis and phase diagram.
AB  - We report on the neutral-to-ionic (N-I) phase transition in the one-dimensional
      organic complex (BEDT-TTF)-(ClMeTCNQ). The X-ray studies at room temperature show
      that the neutral phase of (BEDT-TTF)-(ClMeTCNQ) is already characterized by a
      polar long-range ordering, at variance with other charge-transfer compounds
      comprising noncentrosymmetric molecules. From a detailed neutron diffraction
      study of this complex under high pressure, we present the phase diagram of the N
      I transition down to the quantum limit. We discuss the symmetry breaking
      associated with the transition and the evolution of its first-order character
      under pressure.

PMID- 17503801
TI  - Solvation in binary mixtures of water and polar aprotic solvents: theoretical
      calculations of the concentrations of solvent-water hydrogen-bonded species and
      application to thermosolvatochromism of polarity probes.
AB  - Thermo-solvatochromism of two polarity probes, 2,6-diphenyl-4-(2,4,6-triphenyl-
      pyridinium-1-yl)phenolate, RB, and 2,6-dichloro-4-(2,4,6-triphenylpyridinium-1
      yl) phenolate, WB, in aqueous acetone, Me2CO, and aqueous dimethylsulfoxide,
      DMSO, has been studied. The data obtained have been analyzed according to a
      recently introduced solvation model that explicitly considers the presence of 1:1
      organic solvent-water hydrogen-bonded species, S-W, in the bulk binary mixture
      and its exchange equilibria with (S) and (W) in the solvation shell of the probe.
      Calculations require reliable values of Kdissoc, the dissociation constant of S
      W. Previously, this has been calculated from the dependence of the densities of
      binary solvent mixtures on their composition. Using iteration, the volume of the
      hydrogen-bonded species, VS-W, and Kdissoc were obtained simultaneously from the
      same set of experimental data. This approach may be potentially suspect because
      Kdissoc, and VS-W are highly correlated. Therefore, we extended a recently
      introduced approach for the calculation of Valcohol-W to binary mixtures of water
      with acetone, acetonitrile, N,N-dimethylformamide, DMSO, and pyridine. This
      approach includes: Determination of VS-W from ab initio calculations by the COSMO
      solvation model; correction of these volumes for the nonideal behavior of the
      binary solvent mixtures at different temperatures; use of corrected VS-W as a
      constant (not an adjustable parameter) in the equation that is employed to
      calculate Kdissoc (from density versus binary solvent composition). Solvation of
      RB and WB by Me2CO-W showed different behavior from that of aqueous DMSO. Thus,
      water is able to displace Me2CO more efficiently than DMSO from the probe
      solvation shell. Me2CO-W and DMSO-W displace their corresponding precursor
      solvents; this is more efficient for the former case because the strong DMSO-W
      interactions attenuate the solvation capacity of this species. Temperature
      increase resulted in desolvation of both probes, due to concomitant decrease of
      the structures of the component solvents.

PMID- 17503802
TI  - Catalytic mechanism and metal specificity of bacterial peptide deformylase: a
      density functional theory QM/MM study.
AB  - Bacterial peptide deformylase (PDF) represents a novel class of mononuclear iron
      peptidase, and has an intriguing metal preference different from most other
      metalloproteases. Using a hybrid density functional theory (B3LYP) QM/MM method,
      we have theoretically investigated its catalytic mechanism and metal specificity
      by studying both Fe2+-PDF and Zn2+-PDF. In both forms of PDF, the conserved
      Glu133 residue is protonated in the reactant complex, and acts as a general acid
      during the reaction. The initial reaction step is the nucleophilic attack of the
      metal-bound hydroxide on the carbonyl carbon of the substrate. Our calculations
      indicate that the metal ion in Fe2+-PDF is always pentacoordinated during the
      reaction process, while that in Zn2+-PDF is only tetrahedrally coordinated and
      not bound to the substrate in the reactant complex. This difference in their
      metal coordination is suggested to account for the lower activity of Zn2+-PDF in
      comparison with Fe2+-PDF.

PMID- 17503803
TI  - Local probe and conduction distribution of proton exchange membranes.
AB  - Proton exchange membranes (Nafion) have been studied using current sensing atomic
      force microscopy to examine the correlation between the surface morphology and
      the ionic domains, and to probe the local ionic conduction distribution in the
      membranes. It is found that the local ionic conduction generated from the current
      sensing images follows a Gaussian-like distribution, with the peak value and the
      width of the distribution increasing with the relative humidity in the sample
      chamber and, thus, the water content in the membranes. Two types of Nafion
      membranes, Nafion 112 and Nafion 117, were studied using the method. The
      implications of the distribution in relation to the ionic conducting channels in
      the membranes are discussed.

PMID- 17503804
TI  - Energy transfer, excited-state deactivation, and exciplex formation in artificial
      caroteno-phthalocyanine light-harvesting antennas.
AB  - We present results from transient absorption spectroscopy on a series of
      artificial light-harvesting dyads made up of a zinc phthalocyanine (Pc)
      covalently linked to carotenoids with 9, 10, or 11 conjugated carbon-carbon
      double bonds, referred to as dyads 1, 2, and 3, respectively. We assessed the
      energy transfer and excited-state deactivation pathways following excitation of
      the strongly allowed carotenoid S2 state as a function of the conjugation length.
      The S2 state rapidly relaxes to the S* and S1 states. In all systems we detected
      a new pathway of energy deactivation within the carotenoid manifold in which the
      S* state acts as an intermediate state in the S2-->S1 internal conversion pathway
      on a sub-picosecond time scale. In dyad 3, a novel type of collective carotenoid
      Pc electronic state is observed that may correspond to a carotenoid excited
      state(s)-Pc Q exciplex. The exciplex is only observed upon direct carotenoid
      excitation and is nonfluorescent. In dyad 1, two carotenoid singlet excited
      states, S2 and S1, contribute to singlet-singlet energy transfer to Pc, making
      the process very efficient (>90%) while for dyads 2 and 3 the S1 energy transfer
      channel is precluded and only S2 is capable of transferring energy to Pc. In the
      latter two systems, the lifetime of the first singlet excited state of Pc is
      dramatically shortened compared to the 9 double-bond dyad and model Pc,
      indicating that the carotenoid acts as a strong quencher of the phthalocyanine
      excited-state energy.

PMID- 17503805
TI  - Ultrafast electron-induced desorption of water from nanometer amorphous solid
      water films.
AB  - Laser-induced desorption of water molecules from nanometer amorphous solid water
      films supported on a single-crystal platinum substrate is reported. A femtosecond
      laser pulse creates hot substrate electrons, which are injected into the water
      layer, resulting in significant desorption at the water-vacuum interface. The
      dependence of the desorption yield on film thickness and results for isotopic
      spacer and capping layers reveal that the desorbing water originates from
      relatively deep down into the water layer, i.e., from several nanometers below
      the surface. This is proposed to be the result of cooperative electronic effects
      resulting from the high electron densities in the thin water film, which cause a
      transient destabilization of the water H-bonded network. Motion of excited water
      molecules through the layer is enabled by mixing within the layer on ultrafast
      timescales during the desorption process.

PMID- 17503806
TI  - Aromatic-aromatic interaction between 2,3,5-triphenyl-2H-tetrazolium chloride and
      poly(sodium 4-styrenesulfonate).
AB  - Aromatic-aromatic interactions are found between the cationic molecule 2,3,5
      triphenyl-2H-tetrazolium chloride (TTC) and the molecule poly(sodium 4
      styrenesulfonate) (PSS) which makes the overall interaction of TTC with PSS more
      intense than the interaction with other polyanions containing sulfonate groups
      and produces a decrease on the redox ability of TTC. Diafiltration was used to
      compare the binding of TTC to PSS, poly(sodium vinylsulfonate) (PVS), and the
      more hydrophobic poly(sodium 2-(N-acrylamido)-2-methyl-propanesulfonate) (PAMPS).
      The UV-vis spectrum of TTC is changed in the presence of the aromatic polyanion.
      The 1H NMR signals of TTC are broadened and shifted in the presence of PSS,
      suggesting the occurrence of pi-pi interactions. Moreover, nuclear Overhauser
      effects (NOE) between the TTC and PSS protons are found. Possible structures for
      the complex are proposed.

PMID- 17503807
TI  - Photoinduced electron and proton transfer in the hydrogen-bonded pyridine-pyrrole
      system.
AB  - We present here a detailed analysis of the mechanism of photoinduced electron and
      proton transfer in the planar pyrrole-pyridine hydrogen-bonded system, a model
      for the photochemistry of hydrogen bonds in DNA base pairs. Two different
      crossings, an avoided crossing and a conical intersection, are the key steps for
      forward and backward electron and proton transfer providing to the system
      photostability against UV radiation by restoring the system in its initial
      electronic and geometric structure.

PMID- 17503808
TI  - Uranyl coordination in ionic liquids: the competition between ionic liquid
      anions, uranyl counterions, and Cl- anions investigated by extended X-ray
      absorption fine structure and UV-visible spectroscopies and molecular dynamics
      simulations.
AB  - The first coordination sphere of the uranyl cation in room-temperature ionic
      liquids (ILs) results from the competition between its initially bound
      counterions, the IL anions, and other anions (e.g., present as impurities or
      added to the solution). We present a joined spectroscopic (UV-visible and
      extended X-ray absorption fine structure)-simulation study of the coordination of
      uranyl initially introduced either as UO2X2 salts (X-=nitrate NO3-, triflate TfO
      , perchlorate ClO4-) or as UO2(SO4) in a series of imidazolium-based ILs (C4mimA,
      A-=PF6-, Tf2N-, BF4- and C4mim=1-methyl-3-butyl-imidazolium) as well as in the
      Me3NBuTf2N IL. The solubility and dissociation of the uranyl salts are found to
      depend on the nature of X- and A-. The addition of Cl- anions promotes the
      solubilization of the nitrate and triflate salts in the C4mimPF6 and the C4mimBF4
      ILs via the formation of chloro complexes, also formed with other salts. The
      first coordination sphere of uranyl is further investigated by molecular dynamics
      (MD) simulations on associated versus dissociated forms of UO2X2 salts in C4mimA
      ILs as a function of A- and X- anions. Furthermore, the comparison of UO2Cl(4)2-,
      2 X- complexes with dissociated X- anions, to the UO2X2, 4 Cl- complexes with
      dissociated chlorides, shows that the former is more stable. The case of fluoro
      complexes is also considered, as a possible result of fluorinated IL anion's
      degradation, showing that UO2F42- should be most stable in solution. In all
      cases, uranyl is found to be solvated as formally anionic UO2XnAmClp2-n-m-p
      complexes, embedded in a cage of stabilizing IL imidazolium or ammonium cations.

PMID- 17503809
TI  - Carbon-fluorine bond cleavage in the preparation of Osmium(III) and Osmium(IV)
      fluorothiolate complexes. Fluorine by fluorine NMR-assignment and fluxional
      processes.
AB  - Reactions of OsO4 with HSR (R=C6F5, C6F4H-4,) in refluxing ethanol afford
      [Os(SC6F5)3(SC6F4(SC6F5)-2)] (1) and [Os(SC6F4H-4)3(SC6F3H-4-(SC6F4H-4)-2)] (2),
      which involve the rupture of C-F bonds. At room temperature, the compound
      [Os(SC6F5)3(PMe2Ph)2] or [Os(SC6F5)4(PMe2Ph)] reacts with KOH(aq) in acetone,
      giving rise to [ Os(SC6F5)(SC6F4(SC6F4O-2)-2)(PMe2Ph)2] (3), through a process
      involving the rupture of two C-F bonds, while the compound [Os(SC6F4H)4(PPh3)]
      reacts with KOH(aq) in acetone to afford [Os(SC6F4H-4)2(SC6F3H-4-O-2)(PPh3)] (4),
      which also implies a C-F bond cleavage. Single-crystal X-ray diffraction studies
      of 1, 2, and 4 indicate that these compounds include five-coordinated metal ions
      in essentially trigonal-bipyramidal geometries, whereas these studies on the
      paramagnetic compound 3 show a six-coordinated osmium center in a distorted
      octahedral geometry. 19F, 1H, 31P{1H}, and COSY 19F-19F NMR studies for the
      diamagnetic 1, 2, and 4 compounds, including variable-temperature 19F NMR
      experiments, showed that these molecules are fluxional. Some of the activation
      parameters for these dynamic processes have been determined.

PMID- 17503810
TI  - Copper-homoscorpionate complexes as active catalysts for atom transfer radical
      addition to olefins.
AB  - Cu(I) complexes containing trispyrazolylborate ligands efficiently catalyze the
      atom transfer radical addition (ATRA) of polyhalogenated alkanes to various
      olefins under mild conditions. The catalytic activity is enhanced when bulky and
      electron donating Tpx ligands are employed. Kinetic data have allowed the
      proposal of a mechanistic interpretation that includes a Cu(II) pentacoordinated
      species that regulates the catalytic cycle.

PMID- 17503812
TI  - Synthesis and structural characterization of C(OTeF5)4 and a comparative
      structural study of the isoelectronic B(OTeF5)4- anion.
AB  - Tetrakis(pentafluoroorthotellurate)carbon(IV), C(OTeF5)4, was synthesized by
      reaction of CBr4 with BrOTeF5 in SO2ClF solution at -78 degrees C and was
      isolated as a colorless, crystalline solid that is room-temperature stable in
      SO2ClF and in the solid state. Both natural abundance and 99% 13C-enriched
      C(OTeF5)4 have been characterized in SO2ClF solution by 13C, 19F, and 125Te NMR
      spectroscopy. In contrast, C(OTeF5)4 undergoes rapid decomposition to O(TeF5)2
      and CO2 in CH3CN at 10 degrees C but is stable at -40 degrees C. The X-ray
      crystal structures of C(OTeF5)4 and [N(CH3)4][B(OTeF5)4] were determined at -30
      and -170 degrees C, respectively. The averages of four smaller C/B-O-Te bond
      angles and O...O contacts and two larger C/B-O-Te bond angles and O...O contacts
      of C(OTeF5)4 and the isoelectronic B(OTeF5)4- anion are consistent with local S4
      symmetry, as predicted by ligand close packing considerations. The existence of
      three sets of Te-O-C/B-O torsion angles and the energy-minimized geometries of
      C(OTeF5)4 and B(OTeF5)4- also confirm their local S4 symmetries. The low
      temperature, solid-state Raman spectra of 12/13C(OTeF5)4 and B(OTeF5)4- were
      assigned and compared. The energy-minimized geometries, vibrational frequencies,
      natural charges, and natural bond orders of both species have been calculated
      using density functional theory methods. The calculated geometries are in accord
      with the S4 symmetries assigned for the experimental structures.

PMID- 17503811
TI  - 1,2,3-triazolate-bridged tetradecametallic transition metal clusters
      [M14(L)6O6(OMe)18X6] (M=FeIII, CrIII and VIII/IV) and related compounds: ground
      state spins ranging from S=0 to S=25 and spin-enhanced magnetocaloric effect.
AB  - We report the synthesis, by solvothermal methods, of the tetradecametallic
      cluster complexes [M14(L)6O6(OMe)18Cl6] (M=FeIII, CrIII) and [V14(L)6O6(OMe)18Cl6
      xOx] (L=anion of 1,2,3-triazole or derivative). Crystal structure data are
      reported for the {M14} complexes [Fe14(C2H2N3)6O6(OMe)18Cl6],
      [Cr14(bta)6O6(OMe)18Cl6] (btaH=benzotriazole), [V14O6(Me2bta)6(OMe)18Cl6-xOx]
      [Me2btaH=5,6-Me2-benzotriazole; eight metal sites are VIII, the remainder are
      disordered between {VIII-Cl}2+ and {VIV=O}2+] and for the distorted
      [FeIII14O9(OH)(OMe)8(bta)7(MeOH)5(H2O)Cl8] structure that results from non
      solvothermal synthetic methods, highlighting the importance of temperature regime
      in cluster synthesis. Magnetic studies reveal the {Fe14} complexes to have ground
      state electronic spins of S<or=25, among the highest known, while in contrast the
      {Cr14} complex has an S=0 ground state despite having a very similar structure
      and all complexes being dominated by intramolecular antiferromagnetic exchange
      interactions. The {Fe14} complexes undergo a magnetic phase transition to long
      range ordering at relatively high temperatures for molecular species, which are
      governed by the steric bulk of the triazole (TN=1.8 and 3.4 K for L=bta- and
      H2C2N3-, respectively). The huge spins of the {Fe14} complexes lead to very large
      magnetocaloric effects (MCE)-the largest known for any material below 10 K-which
      is further enhanced by spin frustration within the molecules due to the competing
      antiferromagnetic interactions. The largest MCE is found for
      [Fe14(C2H2N3)6O6(OMe)18Cl6] with an isothermal magnetic entropy change -DeltaSm
      of 20.3 J kg-1 K-1 at 6 K for an applied magnetic field change of 0-7 T.

PMID- 17503813
TI  - Palladium complexes of perylene diimides: strong fluorescence despite direct
      attachment of late transition metals to organic dyes.
AB  - We prepared the first sigma-bonded metal complexes of widely utilized organic
      dyes, perylene tetracarboxylic acid diimides (PDIs). These 1,7-dipalladium PDI
      complexes were synthesized by C-Br oxidative addition of 1,7-dibromo-N,N'
      dicyclohexyl PDI (Br2PDI) to Pd(0) phosphine complexes bearing triphenylphosphine
      and bischelating 1,2-bis(diphenylphosphino)ethane (dppe). The structures of Pd
      PDI complexes were elucidated by single-crystal X-ray analysis. Surprisingly,
      despite direct attachement of two late transition metal centers, Pd-PDI systems
      are highly fluorescent (Phi=0.65 and 0.22 for triphenylphosphine and dppe
      systems, respectively). This is rationalized in terms of weak electronic
      interactions between the metal centers and PDI pi-system, as revealed by TD-DFT
      calculations.

PMID- 17503815
TI  - Photochromism of mixed crystals containing bisthienyl-, bisthiazolyl-, and
      bisoxazolylethene derivatives.
AB  - Single crystals composed of two or three different kinds of diarylethenes, having
      similar geometrical structures but different colors in the closed-ring isomers,
      1,2-bis(2-methyl-5-phenyl-3-thienyl)perfluorocyclopentene (1a), 1,2-bis(5-methyl
      2-phenyl- 4-thiazolyl)perfluorocyclopentene (2a), and 1,2-bis(5-methyl-2-phenyl-4
      oxazolyl)perfluorocyclopentene (3a) have been prepared in an attempt to form
      single crystals which exhibit different colors, depending on illumination
      wavelengths. When 1a and 2a are mixed in ethanol and the content of 2a in the
      feed is higher than that of 1a, only a needle-shaped crystal is obtained. The
      crystal shape is similar to that of 2a. On the other hand, high content of 1a in
      the feed leads to formation of a block-shaped crystal, of which the shape is
      similar to that of 1a. At a feed ratio of 1:1 for 1a and 2a, two types of
      crystals such as needle- and block-shapes are obtained from the same batch. Mixed
      crystals composed of three kinds of derivatives 1a/2a/3a have also been prepared.
      A crystal composed of the three derivatives in the molar ratio of 32 (1a):53
      (2a):15 (3a) was obtained. X-ray analysis proved that 1a and 3a are packed in the
      crystal lattice of 2a. The mixed crystal 1a/2a/3a changed color from colorless to
      yellow, red, and blue upon irradiation with light of appropriate wavelengths.

PMID- 17503816
TI  - Regulation of orthogonal functions in a dual catalyst system. Subservient role of
      a nonchiral Lewis acid in an asymmetric catalytic heteroatom Diels-Alder
      reaction.

PMID- 17503817
TI  - Shape-controlled conversion of beta-Sn nanocrystals into intermetallic M-Sn
      (M=Fe, Co, Ni, Pd) nanocrystals.
AB  - The ability to control the shape of metal nanocrystals is critical to
      applications such as catalysis, magnetism, and plasmonics. Despite significant
      advances in controlling the shapes of single-metal nanocrystals, rigorous shape
      control of multimetal nanocrystals remains challenging, and has been limited
      largely to alloy systems of similar metals. Here we describe a robust strategy
      that produces shape-controlled intermetallic nanocrystals involving elements of
      notably different reduction potentials, reduction kinetics, and reactivity. The
      approach utilizes shape- and size-controlled beta-Sn nanocrystals as reactive
      templates that can be converted into binary M-Sn (M=Fe, Co, Ni, Pd) intermetallic
      compounds by reaction with appropriate metal salt solutions under reducing
      conditions. The result, demonstrated in detail for the FeSn2 system, is a variety
      of nanostructures with morphologies that include spheres, cubes, hollow squares,
      U-shaped structures, nanorods, and nanorod dimers. Our experiments demonstrate a
      size- and shape-dependent reactivity toward the formation of hollow FeSn2
      nanostructures and provide empirical guidelines for the formation of other
      intermetallic nanocrystals. In addition to those of FeSn2, nanocrystals of
      intermetallic PdSn, CoSn3, and NiSn3 can be formed using this same chemical
      conversion strategy.

PMID- 17503818
TI  - Solid-phase synthesis of multiple classes of peptidomimetics from versatile resin
      bound aldehyde intermediates.
AB  - A wide variety of highly substituted lactam containing peptidomimetic scaffolds
      are prepared by solid-phase synthesis from a single, versatile class of resin
      bound aldehyde intermediates (1). These include monocyclics 3, bicyclics 4,
      tricyclics 5, and tetracyclics 6. The key intermediate 1 is readily synthesized
      from resin-bound natural or unnatural alpha-amino acids. The synthetic procedures
      permit the construction of a large diversity of substitution patterns for ready
      use in combinatorial chemistry. In every case, the release of final products from
      resin is by a cyclitive cleavage process. Since this depends on successful
      completion of multiple intermediate synthetic steps, the products are often quite
      pure, even though previous steps involve only a filtration workup. The mild
      conditions for many of these synthetic procedures offer the promise of using this
      chemistry in peptide fragment condensations to produce modified peptides, at
      either the N-terminus or C-terminus, or as individually assembled peptide
      segments with a wide variety of conformationally restricted peptidomimetic
      linkers at the point of juncture.

PMID- 17503819
TI  - Interactions between hydrophobic and ionic solutes in aqueous guanidinium
      chloride and urea solutions: lessons for protein denaturation mechanism.
AB  - In order to clarify the mechanism of denaturant-induced unfolding of proteins we
      have calculated the interactions between hydrophobic and ionic species in aqueous
      guanidinium chloride and urea solutions using molecular dynamics simulations.
      Hydrophobic association is not significantly changed in urea or guanidinium
      chloride solutions. The strength of interaction between ion pairs is greatly
      diminished by the guanidinium ion. Although the changes in electrostatic
      interactions in urea are small, examination of structures, using appropriate pair
      functions, of urea and water around the solutes show strong hydrogen bonding
      between urea's carbonyl oxygen and the positively charged solute. Our results
      strongly suggest protein denaturation occurs by the direct interaction model
      according to which the most commonly used denaturants unfold proteins by altering
      electrostatic interactions either by solvating the charged residues or by
      engaging in hydrogen bonds with the protein backbone. To further validate the
      direct interaction model we show that, in urea and guanidinium chloride
      solutions, unfolding of an unusually stable helix (H1) from mouse PrPC (residues
      144-153) occurs by hydrogen bonding of denaturants to charged side chains and
      backbone carbonyl groups.

PMID- 17503820
TI  - Influence of connectivity and porosity on ligand-based luminescence in zinc metal
      organic frameworks.
AB  - Applications of metal-organic frameworks (MOFs) require close correlation between
      their structure and function. We describe the preparation and characterization of
      two zinc MOFs based on a flexible and emissive linker molecule, stilbene, which
      retains its luminescence within these solid materials. Reaction of trans-4,4'
      stilbene dicarboxylic acid and zinc nitrate in N,N-dimethylformamide (DMF)
      yielded a dense 2-D network, 1, featuring zinc in both octahedral and tetrahedral
      coordination environments connected by trans-stilbene links. Similar reaction in
      N,N-diethylformamide (DEF) at higher temperatures resulted in a porous, 3-D
      framework structure, 2. This framework consists of two interpenetrating cubic
      lattices, each featuring basic zinc carboxylate vertices joined by trans
      stilbene, analogous to the isoreticular MOF (IRMOF) series. We demonstrate that
      the optical properties of both 1 and 2 correlate with the local ligand
      environments observed in the crystal structures. Steady-state and time-resolved
      spectroscopic measurements reveal that the stilbene linkers in the dense
      structure 1 exhibit a small degree of interchromophore coupling. In contrast, the
      stilbenoid units in 2 display very little interaction in this low-density 3-D
      framework, with excitation and emission spectra characteristic of monomeric
      stilbenes, similar to the dicarboxylic acid in dilute solution. In both cases,
      the rigidity of the stilbene linker increases upon coordination to the inorganic
      units through inhibition of torsion about the central ethylene bond, resulting in
      luminescent crystals with increased emission lifetimes compared to solutions of
      trans-stilbene. The emission spectrum of 2 is found to depend on the nature of
      the incorporated solvent molecules, suggesting use of this or related materials
      in sensor applications.

PMID- 17503821
TI  - NIR-emitting colloidal quantum dots having 26% luminescence quantum yield in
      buffer solution.

PMID- 17503822
TI  - Temperature sensitivity control of alkylamide-terminated poly(amidoamine)
      dendrimers induced by guest molecule binding.

PMID- 17503823
TI  - Catalytic enantioselective alkylative aldol reaction: efficient multicomponent
      assembly of dialkylzincs, allenic esters, and ketones toward highly
      functionalized delta-lactones with tetrasubstituted chiral centers.
AB  - A general catalytic asymmetric alkylative aldol reaction is described as a new
      entry to the catalytic asymmetric multicomponent reaction (CAMCR). Highly
      functionalized delta-lactones were produced in the presence of a catalytic amount
      of the Cu(OAc)2-DIFLUORPHOS complex through three-component assembly of
      dialkylzincs, allenic esters, and unactivated ketones. This CAMCR constructs two
      C-C bonds and one tetrasubstituted chiral center simultaneously. Conjugate
      addition of alkylcopper species to an allenic ester produced highly active copper
      enolate in situ, and the successive asymmetric aldol addition to ketones followed
      by lactonization afforded the desired products. The addition of MS4A and Lewis
      base (Ph2S=O, DMSO, or HMPA) is important for obtaining a high yield, with
      suppression of the undesired alpha-addition pathway. Control/crossover
      experiments suggest that the addition of a Lewis base facilitated the retro-aldol
      reaction of the alpha-adducts (proofreading effect). The ketone and copper
      enolate generated through the retro-aldol reaction were converted to the desired
      lactone through the gamma-aldol pathway, which was trapped by irreversible
      lactone formation.

PMID- 17503824
TI  - Aromatic hydroxylation reactivity of a mononuclear Cu(II)-alkylperoxo complex.

PMID- 17503827
TI  - Molecular insight into the pathway to crystallization of aluminum.

PMID- 17503826
TI  - A Small synthetic molecule forms chloride channels to mediate chloride transport
      across cell membranes.

PMID- 17503828
TI  - Smart aptamers facilitate multi-probe affinity analysis of proteins with ultra
      wide dynamic range of measured concentrations.

PMID- 17503829
TI  - Nanometer-sized amino acids for the synthesis of nanometer-scale water-soluble
      molecular rods of precise length.

PMID- 17503830
TI  - A calorimetric study of thermal denaturation of recombinant human lactoferrin
      from rice.
AB  - Thermal denaturation of recombinant human lactoferrin from transgenic rice with
      different degrees of iron saturation has been studied by differential scanning
      calorimetry. The maximum temperature, enthalpy change, and activation energy of
      denaturation were higher when recombinant lactoferrin was more saturated with
      iron, indicating an increase in the stability of the protein structure. Maximum
      temperature and activation energy values for apo- and holo-lactoferrins were
      practically identical to those reported for the same forms of lactoferrin from
      human milk, which indicates a similar thermal stability. However, the value of
      enthalpy change for denaturation of the recombinant lactoferrin was 2.5-3-fold
      lower than that found for the human milk protein. This finding may reflect the
      influence that the different glycosylation pattern may have in the relationship
      between lactoferrin domains. Denaturation of recombinant lactoferrin in milk was
      compared with denaturation in phosphate buffer, and results indicated that the
      protein was more heat-sensitive when treated in milk than in buffer.

PMID- 17503831
TI  - Quantification of chlorophyll content and classification of nontransgenic and
      transgenic tomato leaves using visible/near-infrared diffuse reflectance
      spectroscopy.
AB  - Visible/near-infrared (vis/NIR) spectroscopy combined with multivariate analysis
      was used to quantify chlorophyll content in tomato leaves and classify tomato
      leaves with different genes. In this study, transgenic tomato leaves with
      antisense LeETR1 (n = 106) and their parent nontransgenic ones (n = 102) were
      measured in vis/NIR diffuse reflectance mode. Quantification of chlorophyll
      content was achieved by partial least-squares regression with a cross-validation
      prediction error equal to 2.87. Partial least-squares discriminant analysis was
      performed to classify leaves. The results show that differences between
      transgenic and nontransgenic tomato leaves do exist, and excellent classification
      can be obtained after optimizing spectral pretreatment. The classification
      accuracy can reach to 100% using the derivative of spectral data in the full and
      partial wavenumber range. These results demonstrate that vis/NIR spectroscopy
      together with chemometrics techniques could be used to quantify chlorophyll
      content and differentiate tomato leaves with different genes, which offers the
      benefit of avoiding time-consuming, costly, and laborious chemical and sensory
      analysis.

PMID- 17503832
TI  - Why do gelatinized starch granules not dissolve completely? Roles for amylose,
      protein, and lipid in granule "ghost" integrity.
AB  - After gelatinization in water, starch granules persist in swollen hydrated forms
      known as ghosts. Three potential mechanisms for ghost formation are tested.
      Proteins and lipids on the granule surface are found to be a determinant of ghost
      robustness, but not ghost formation. Proteins inside pre-made maize or wheat
      starch ghosts are degraded extensively by proteases without any apparent change
      in ghost properties, making an internal protein cross-linking mechanism unlikely.
      Waxy maize mutants with a range of amylose contents have ghost integrities that
      correlate with (low) apparent amylose levels. It is hypothesized that ghost
      formation is due to cross-linking of polysaccharide chains within swollen
      granules, most likely involving double helices formed from polymer chains that
      become free to move following heat-induced granule swelling. The size and
      robustness of granule ghosts is proposed to be determined by the relative rates
      of swelling and cross-linking, modulated by surface non-polysaccharide
      components.

PMID- 17503834
TI  - Studies toward the total synthesis of sorangiolides and their analogues. A
      convergent stereoselective synthesis of the macrocyclic lactone precursors.
AB  - Stereoselective synthesis of the fully protected 18-membered macrocyclic lactones
      as the immediate precursors of the natural products, sorangiolides A and B, is
      described. The key steps used in the synthesis include the sp3-hybridized carbon
      carbon Fu cross coupling, the stereoselective Evans' aldol reaction with 1,5-anti
      induction, the 1,3-diastereoselective syn reduction of a beta-hydroxyketone
      intermediate, and Mukaiyama macrolactonization reactions.

PMID- 17503833
TI  - Interactions between a non glycosylated human proline-rich protein and flavan-3
      ols are affected by protein concentration and polyphenol/protein ratio.
AB  - Interactions between salivary proline-rich proteins and tannins are involved in
      astringency, which is one of the most important organoleptic sensations perceived
      when drinking wine or tea. This work aimed to study interactions between a
      recombinant human salivary proline-rich protein, IB-5, and a flavan-3-ol monomer,
      epigallocatechin gallate (EGCG). IB-5 presented the characteristics of natively
      unfolded proteins. Interactions were studied by dynamic light scattering,
      isothermal titration microcalorimetry, and circular dichroism. The interaction
      mechanism was dependent on protein concentration. At low concentrations, a three
      stage mechanism was evidenced. Saturation of the interaction sites (first stage)
      was followed by protein aggregation into metastable colloids at higher
      EGCG/protein ratios (second stage). Further increasing this ratio led to haze
      formation (third stage). At low ratios, a disorder-to-order transition of IB-5
      structure upon binding was evidenced. At high protein concentrations, direct
      bridging between proteins and EGCG was observed, resulting in significantly lower
      aggregation and turbidity thresholds.

PMID- 17503835
TI  - Negombins A-I, new chlorinated polyfunctional diterpenoids from the marine sponge
      Negombata species.
AB  - Nine novel compounds designated negombins A-I (1-9) were isolated, together with
      latrunculin, from the Tanzanian sponge Negombata sp. The nine are sacculatane
      type diterpenes, previously only known from liverworts. The structures of the
      compounds were elucidated by interpretation of MS and 1D and 2D NMR spectra. A
      possible biogenesis initiated by the naturally rare chloronium ion is suggested,
      possibly hinting to a guest microorganism as the source of the compounds.
      Compound 4 is toxic to brine shrimp larvae.

PMID- 17503836
TI  - The first limonoid peroxide in the Meliaceae family: walsuronoid A from Walsura
      robusta.
AB  - Walsuronoid A (1), a limonoid featuring an unprecedented 3,4-peroxide-bridged A
      seco skeleton, together with walsuronoids B (2) and C (3) possessing a rare 18(13
      ->14)-abeo-limonoid skeleton, was isolated from Walsura robusta. The structures
      were elucidated by spectroscopic analysis and chemical correlation, and that of 1
      was confirmed by single-crystal X-ray diffraction. Biosynthetic pathway of 2 and
      3 was proposed and was chemically mimicked. Compounds 1 and 2 showed weak
      antimalarial activity.

PMID- 17503837
TI  - Stereoselective iodocyclization of (S)-allylalanine derivatives: gamma-lactone vs
      cyclic carbamate formation.
AB  - An efficient procedure for highly chemo- and stereoselective cyclization of (S)
      allylalanine derivatives is reported (diastereomeric ratios up to 96:4) where the
      reaction course can be completely controlled by switching from gamma-lactones to
      cyclic carbamates simply with the proper choice of the amino acid protecting
      groups. Both processes are stereoconvergent and afford the (S,S)-products in high
      yields, short reaction times, and mild reaction conditions.

PMID- 17503838
TI  - Nagelamide J, a novel dimeric bromopyrrole alkaloid from a sponge Agelas species.
AB  - A novel dimeric bromopyrrole alkaloid, nagelamide J (1), with antimicrobial
      activity has been isolated from an Okinawan marine sponge Agelas species, and the
      structure and stereochemistry were elucidated from spectroscopic data. Nagelamide
      J (1) is the first bromopyrrole alkaloid possessing a cyclopentane ring fused to
      an amino imidazole ring.

PMID- 17503839
TI  - A simple but effective ferrocene derivative as a redox, colorimetric, and
      fluorescent receptor for highly selective recognition of Zn2+ ions.
AB  - A new probe, based on a 1,1'-disubstituted ferrocene, senses Zn2+ selectively
      among heavy and transition-metal (HTM) ions through three different channels:
      anodic redox shift of the Fe(II)/Fe(III) redox couple, the orange to deep purple
      color change that is visible to the naked-eye, and a remarkable enhancement of
      the fluorescence.

PMID- 17503840
TI  - Intramolecular SNAr reactions in a large-ring ketocalix[6]arene.
AB  - Ketocalix[6]arene 2e was prepared by CrO3 oxidation of the methylene groups of
      2a, followed by hydrolysis of the acetate groups. 2e undergoes intramolecular
      SNAr reactions under the usual methylation conditions (MeI, base), yielding mono-
      and dixanthone calixarene derivatives.

PMID- 17503841
TI  - Experimental demonstration of base-catalyzed interconversion of isomeric betaine
      intermediates in the Corey-Chaykovsky epoxidation.
AB  - The collapse of hydroxysulfonium salts has been examined as a model for the
      epoxidation of aldehydes. The anti diastereomer reacted with retention of
      stereochemistry and no crossover, while the syn diastereomer gave crossover
      products along with cis and trans epoxides. Deprotonation and reprotonation on
      the carbon of the alpha-hydroxy sulfonium ylide is presumed responsible for
      production of the trans epoxide. This reaction pathway has been proposed to
      explain losses of enantioselectivity but never directly observed.

PMID- 17503842
TI  - Bronsted acid-mediated stereoselective cascade construction of functionalized
      tetrahydropyrans from 2-(arylmethylene)cyclopropylcarbinols and aldehydes.
AB  - (E)- and (Z)-2-(Arylmethylene)cyclopropylcarbinols 1 could be converted to the
      corresponding tetrahydropyrans 2 and 3 stereoselectively in the presence of
      Bronsted acids MsOH or TsOH under mild conditions. A plausible Prins-type
      reaction mechanism has been proposed.

PMID- 17503843
TI  - Efficient one-pot synthesis of highly substituted pyridin-2(1H)-ones via the
      Vilsmeier-Haack reaction of 1-acetyl,1-carbamoyl cyclopropanes.
AB  - A facile and efficient one-pot synthesis of highly substituted pyridin-2(1H)-ones
      is developed via the Vilsmeier-Haack reaction of readily available 1-acetyl,1
      carbamoyl cyclopropanes, and a mechanism involving sequential ring-opening,
      haloformylation, and intramolecular nucleophilic cyclization reactions is
      proposed.

PMID- 17503844
TI  - Glycal glycosylation and 2-nitroglycal concatenation, a powerful combination for
      mucin core structure synthesis.
AB  - A 3,4-O-unprotected galactal derivative having bulky 6-O-TIPS protection
      (compound 2) could be regioselectively 3-O-glycosylated with O-(galactopyranosyl)
      trichloroacetimidates; depending on the protecting group pattern
      stereoselectively alpha- and beta-linked disaccharides were obtained. With O-(2
      azido-2-deoxyglucopyransyl) trichloroacetimidate as donor (compound 10A),
      glycosylation of 2 and of a 6-O-unprotected galactal derivative led in
      acetonitrile as solvent exclusively to a beta(1-3)- and a beta(1-6)-linked
      disaccharide, respectively. Nitration of the galactal moieties of the saccharides
      followed by Michael-type addition of serine and threonine derivatives (7a,b)
      installed the alpha-galacto-configuration, thus readily furnishing O-glycosyl
      amino acid building blocks for the incorporation of core 1, core 2, core 3, core
      6, and core 8 structures into glycopeptides. 2-Nitrogalactal and 2-nitroglucal
      derivatives could be also successfully employed in glycoside bond formation via
      Michael-type addition in a reiterative manner, affording the corresponding core
      5, core 7, and core 6 building blocks. In this approach, highly stereoselective
      glycoside bond formations were based exclusively on Michael-type addition to the
      nitro-enol ether moiety of the 2-nitroglycals. Hence, 2-nitroglycals are
      versatile intermediates for base-catalyzed glycoside bond formation.

PMID- 17503845
TI  - Aromaticity and curvature in heteroacepentalenes.
AB  - Heteroatom-substituted acepentalene derivatives which are isoelectronic with the
      known acepentalenediide dianion are nonplanar, fused aromatic tricycles which are
      hemifullerenes of the corresponding C20 heteroanalogue. Depending on the number
      and position of heteroatoms, they may be anionic, neutral, or cationic. A nucleus
      independent chemical shift study indicates that substitution of the central
      carbon of the acepentalenediide system with N or O results in a substantial
      increase in aromaticity. Peripheral aza substitution on the other hand tends to
      increase curvature and decrease aromaticity. Alkylation or protonation at the
      central position of asymmetrically substituted heteroacepentalenides leads to
      chiral, bowl-shaped, 10 pi aromatic species.

PMID- 17503846
TI  - Oligonucleotides containing 6-aza-2'-deoxyuridine: synthesis, nucleobase
      protection, pH-dependent duplex stability, and metal-DNA formation.
AB  - Oligodeoxyribonucleotides containing the nucleoside 6-aza-2'-deoxyuridine z6Ud
      (1a) were prepared by using solid-phase synthesis. As the pKa value of this
      nucleoside is 6.8, unwanted side reactions are observed. Consequently, nitrogen-3
      was protected (o-anisoyl protection). The phosphoramidite of 1a prepared on this
      route was as efficient as the building blocks of canonical nucleosides in
      allowing multiple incorporations into oligonucleotides. Oligonucleotide duplexes
      containing 1a show a pH dependence of the Tm value. This is caused by nucleobase
      deprotonation occurring on compound 1a already under neutral conditions. Metal
      (M)-DNA formation was studied in the presence of Zn+2 ions. It is demonstrated
      that 6-azauracil-modified duplexes form M-DNA already in neutral medium while
      alkaline conditions (above pH 8.5) are required for natural DNA. The
      conformational analysis of the sugar moiety of the nucleoside 1a and its anisoyl
      derivative 5a shows a preferred N-conformation in solution while an S
      conformation for compound 1a was obtained in the solid state (single-crystal X
      ray analysis).

PMID- 17503847
TI  - Binding modes of cucurbit[6]uril and cucurbit[7]uril with a tetracationic
      bis(viologen) guest.
AB  - Binding behaviors of two cucurbit[n]urils (CB[n]) hosts with the
      [CH3bpy(CH2)6bpyCH3]4+ (bpy = 4,4'-bipyridinium) guest were investigated by 1H
      NMR and MALDI-TOF-MS experiments. While the CB[6] and CB[7] form
      [2]pseudorotaxanes with the host located over the hexamethylene chain of the
      guest, only the CB[7] forms a [3]pseudorotaxane with both host molecules residing
      over the bipyridinium groups. The initial CB[7] host vacates the inclusion of the
      hexamethylene chain as a result of the electrostatic and steric repulsions that
      would arise in simultaneous binding of adjacent aliphatic and aromatic portions
      of the guest.

PMID- 17503848
TI  - Thiacyclophane cages and related bi- and tripodal molecules via transient
      polysulfenic acids.
AB  - A series of bis- and tris-bridged thiacyclophane S-oxides, as racemates or meso
      products, have been synthesized with a new procedure. Starting from the
      corresponding thiols, in three steps, transient polyarene- and polyarylmethane
      sulfenic acids were generated in the presence of di- and triethynylbenzenes. The
      thermal syn-addition of these sulfenic acids onto the triple bonds of the
      unsaturated acceptors was conducted in CH2Cl2 at 40 degrees C. The concentration
      of sulfoxide precursors of sulfenic acid and the sulfoxide/acceptor molar ratio
      addressed the syn-addition toward open-chain benzene sulfoxides or thiacyclophane
      S-oxides. Complete stereochemical control was observed in some reactions between
      polysulfenic acids and ethynylbenzenes, where the meso dithiacyclophane S,S'
      dioxides were obtained exclusively, whereas 1:1 mixtures of meso/rac
      dithiacyclophanes S,S'-dioxides were isolated as products of other reactions. In
      almost all the cases, the obtained compounds were separated by column
      chromatography. The structure assignment of the new heterophanes was done on the
      basis of their diagnostic NMR spectra and X-ray crystallographic analysis of some
      of them. Open-chain polysulfinyl and polysulfinylmethyl benzenes, obtained as
      meso/rac mixtures, were separated and the products were fully characterized. Both
      synthesized cages, including trithia[3(3)](1,3,5)cyclophane S,S',S' '-trioxides,
      and bi- and tripodal benzene sulfoxides, appear promising in the field of
      coordination and material chemistry.

PMID- 17503849
TI  - Concise synthesis of 1,2-dihydroisoquinolines and 1H-isochromenes by carbophilic
      lewis acid-catalyzed tandem nucleophilic addition and cyclization of 2-(1
      alkynyl)arylaldimines and 2-(1-alkynyl)arylaldehydes.
AB  - By using carbophilic Lewis acids, In(OTf)3, NiCl2, and AuCl(PPh3)/AgNTf2, a
      concise and efficient synthesis of 1,3-disubstituted 1,2-dihydroisoquinolines has
      been achieved via tandem nucleophilic addition and cyclization of 2-(1
      alkynyl)arylaldimines. Addition of proton sources such as water, CF3CH2OH, and
      2,6-di-tert-butyl-4-methoxyphenol was essential for the Lewis acid-catalyzed
      tandem reactions with organometallic reagents. By switching these catalysts,
      various types of nucleophiles such as allylstannanes, silyl enol ethers,
      alkenylboronic acids, and active methylene compounds could be introduced at the
      C1 position of 1,2-dihydroisoquinolines in this transformation. Furthermore, this
      method proved to be applicable to the synthesis of 1H-isochromene derivatives via
      the same tandem reaction of 2-(1-alkynyl)arylaldehydes.

PMID- 17503850
TI  - Cancer chemopreventive effects of cycloartane-type and related triterpenoids in
      in vitro and in vivo models.
AB  - Forty-eight natural and semisynthetic cycloartane-type and related triterpenoids
      have been evaluated for their inhibitory effects on Epstein-Barr virus early
      antigen (EBV-EA) activation induced by the tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test
      for anti-tumor promoters. In addition, these triterpenoids have been tested for
      their inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxyimino]
      5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary
      screening test for anti-tumor initiators. All of the compounds tested exhibited
      inhibitory effects on both EBV-EA and NOR 1 activation. Six of these compounds
      having a C-24 hydroxylated side chain, viz., (24R)-cycloart-25-ene-3beta,24-diol
      (9), (24R)-cycloartane-3beta,24,25-triol (11), (24S)-cycloartane-3beta,24,25
      triol (12), (24xi)-24-methylcycloartane-3beta,24,241-triol (14), (24xi)-241
      methoxy-24-methylcycloartane-3beta,24-diol (15), and (24xi)-24,25
      dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others
      tested on both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation.
      Furthermore, compounds 14 and 15 exhibited inhibitory effects on skin tumor
      promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12
      dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

PMID- 17503851
TI  - Fawcettimine-related alkaloids from Lycopodium serratum.
AB  - Five new Lycopodium alkaloids (1-5) having the fawcettimine skeleton were
      isolated from Lycopodium serratum. The structures of the alkaloids were
      elucidated on the basis of spectroscopic analysis. Some alkaloids isolated in
      this and previous studies (1, 2, 5, and 10) were assayed for acetylcholine
      esterase (AChE) inhibitory activity.

PMID- 17503852
TI  - Stabilization of C60 nanoparticles by protein adsorption and its implications for
      toxicity studies.
AB  - Dispersion stability of nanoparticles of C60 under a model condition simulating a
      physiological environment was studied by dynamic light scattering. Although the
      C60 nanoparticles at a concentration of 9.3 x 10(-6) M (6.7 microg/mL) coagulated
      and precipitated out rapidly in phosphate buffered saline, coagulation was
      suppressed completely when HSA was present at concentrations above 1 mg/mL. DLS
      results show that the HSA molecules adsorb onto the surfaces of the C60
      nanoparticles, thereby forming a protective layer, and prevent salt-induced
      coagulation. DLS results also indicate that the HSA molecules take an expanded
      conformation on the surface. Our findings suggest that C60 nanoparticles can be
      stabilized in the physiological environment even if they are not deliberately
      stabilized by using stabilizers and are of significant implications for the on
      going efforts to evaluate the cytotoxicity of C60 nanoparticles in which no such
      effect has been considered.

PMID- 17503853
TI  - Formation of tethered bilayer lipid membranes on gold surfaces: QCM-Z and AFM
      study.
AB  - Recently, tethered bilayer lipid membranes (tBLMs) have shown high potential as
      biomimetic systems due to their high stability and electrical properties, and
      have been used in applications ranging from membrane protein incorporation to
      biosensors. However, the kinetics of their formation remains largely
      uninvestigated. By using quartz crystal microbalance with impedance analysis (QCM
      Z), we were able to monitor both the kinetics and viscoelastic properties of
      tether adsorption and vesicle fusion. Formation of the tether monolayer was shown
      to follow pseudo-first-order Langmuir kinetics with association and dissociation
      rate constants of 21.7 M-1 s(-1) and 7.43 x 10-6 s(-1), respectively. Moreover,
      the QCM-Z results indicate a rigid layer at the height of deposition, which then
      undergoes swelling as indicated by AFM. The deposition of vesicles to the tether
      layer also followed pseudo-first-order Langmuir kinetics with observed rate
      constants of 5.58 x 10(-2) and 2.41 x 10-2 s(-1) in water and buffer,
      respectively. Differential analysis of the QCM-Z data indicated deposition to be
      the fast kinetic step, with the rate-limiting steps being water release and
      fusion. Atomic force microscopy pictures taken complement the QCM-Z data, showing
      the major stages of tether adsorption and vesicle fusion, while providing a road
      map to successful tBLM formation.

PMID- 17503854
TI  - Dual magnetic-/temperature-responsive nanoparticles for microfluidic separations
      and assays.
AB  - A stimuli-responsive magnetic nanoparticle system for diagnostic target capture
      and concentration has been developed for microfluidic lab card settings.
      Telechelic poly(N-isopropylacrylamide) (PNIPAAm) polymer chains were synthesized
      with dodecyl tails at one end and a reactive carboxylate at the opposite end by
      the reversible addition fragmentation transfer technique. These PNIPAAm chains
      self-associate into nanoscale micelles that were used as dimensional confinements
      to synthesize the magnetic nanoparticles. The resulting superparamagnetic
      nanoparticles exhibit a gamma-Fe2O3 core ( approximately 5 nm) with a layer of
      carboxylate-terminated PNIPAAm chains as a corona on the surface. The carboxylate
      group was used to functionalize the magnetic nanoparticles with biotin and
      subsequently with streptavidin. The functionalized magnetic nanoparticles can be
      reversibly aggregated in solution as the temperature is cycled through the
      PNIPAAm lower critical solution temperature (LCST). While the magnetophoretic
      mobility of the individual nanoparticles below the LCST is negligible, the
      aggregates formed above the LCST are large enough to respond to an applied
      magnetic field. The magnetic nanoparticles can associate with biotinylated
      targets as individual particles, and then subsequent application of a combined
      temperature increase and magnetic field can be used to magnetically separate the
      aggregated particles onto the poly(ethylene glycol)-modified polydimethylsiloxane
      channel walls of a microfluidic device. When the magnetic field is turned off and
      the temperature is reversed, the captured aggregates redisperse into the channel
      flow stream for further downstream processing. The dual magnetic- and temperature
      responsive nanoparticles can thus be used as soluble reagents to capture
      diagnostic targets at a controlled time point and channel position. They can then
      be isolated and released after the nanoparticles have captured target molecules,
      overcoming the problem of low magnetophoretic mobility of the individual particle
      while retaining the advantages of a high surface to volume ratio and faster
      diffusive properties during target capture.

PMID- 17503855
TI  - Complex desorption of mucin from silica.
AB  - Complex solutes may adsorb from solution onto solid surfaces in a concentration
      dependent manner. In other words, the adsorption behavior is qualitatively
      different in different bulk concentration regimes. Here we show that the large
      glycoprotein mucin not only adsorbs in distinctively different ways according to
      the bulk concentration but also, strikingly, that the law of desorption,
      established with the help of high-resolution molecular microscopy, depends on the
      bulk concentration during adsorption. Making use of supporting bulk rheology data
      delineating the entangled regime and atomic force microscopy images of the
      adsorbed layers corroborating the existence of a bilayer structure formed at
      higher bulk concentrations, a tentative molecular mechanism for the observations
      is proposed.

PMID- 17503856
TI  - Water surface covering of fluorinated amphiphilic triblock copolymers: surface
      pressure-area and X-ray reflectivity investigations.
AB  - Monolayers of ABA amphiphilic triblock block copolymers are studied using surface
      pressure-area and X-ray reflectivity (XR) measurements. The triblock copolymers
      are composed of long poly(ethylene oxide) (PEO) middle blocks with
      poly((perfluorohexyl)ethyl methacrylate) (PFMA) end blocks. The surface pressure
      area isotherms of water-insoluble species show two pseudoplateaus. The plateau at
      low surface pressure is consistent with the pseudoplateau observed for PEO
      copolymers in the literature. The plateau in the brush region can be assigned to
      the horizontal to vertical rearrangement of whole PFMA chains at the air-water
      interface, which was followed by XR measurements. For water-soluble species with
      a very low amount of PFMA no (significant) second pseudoplateau and no enrichment
      of PFMA at the air-water interface were observed.

PMID- 17503857
TI  - Characterization of nanobubbles on hydrophobic surfaces in water.
AB  - The aim of this paper is to quantitatively characterize the appearance,
      stability, density, and shape of surface nanobubbles on hydrophobic surfaces
      under varying conditions such as temperature and temperature variation, gas type
      and concentration, surfactants, and surface treatment. The method we adopt is
      atomic force microscopy (AFM) operated in the tapping mode. In particular, we
      show (i) that nanobubbles can slide along grooves under the influence of the AFM
      tip, (ii) that nanobubbles can spontaneously form by substrate heating, allowing
      for a comparison of the surface topology with and without the nanobubble, (iii)
      that a water temperature increase leads to a drastic increase in the nanobubble
      density, (iv) that pressurizing the water with CO2 also leads to a larger
      nanobubble density, but typically to smaller nanobubbles, (v) that alcohol
      cleaning of the surface is crucial for the formation of surface nanobubbles, (vi)
      that adding 2-butanol as surfactant leads to considerably smaller surface
      nanobubbles, and (vii) that flushing water over alcohol-covered surfaces strongly
      enhances the formation of surface nanobubbles.

PMID- 17503858
TI  - Picoliter water contact angle measurement on polymers.
AB  - Water contact angle measurement is the most common method for determining a
      material's wettability, and the sessile drop approach is the most frequently
      used. However, the method is generally limited to macroscopic measurements
      because the base diameter of the droplet is usually greater than 1 mm. Here we
      report for the first time on a dosing system to dispense smaller individual
      droplets with control of the position and investigate whether water contact
      angles determined from picoliter volume water droplets are comparable with those
      obtained from the conventional microliter volume water droplets. This
      investigation was conducted on a group of commonly used polymers. To demonstrate
      the higher spatial resolution of wettability that can be achieved using picoliter
      volume water droplets, the wettability of a radial plasma polymer gradient was
      mapped using a 250 microm interval grid.

PMID- 17503859
TI  - Redox reactions of ferricyanide ions in layer-by-layer deposited polysaccharide
      films: a significant effect of the type of polycation in the films.
AB  - Redox reactions of ferricyanide ions, [Fe(CN)6]3-, in polysaccharide thin films
      that were prepared by layer-by-layer (LbL) deposition on the surface of a gold
      electrode were studied electrochemically by cyclic voltammetry. LbL films
      composed of alginic acid (AGA) and carboxymethylcellulose (CMC) were successfully
      prepared using poly(ethyleneimine) (PEI) and poly(diallyldimethylammonium
      chloride) (PDDA) as the cationic counterparts in the electrostatic LbL
      deposition. The deposition behavior of the PEI-based films significantly depended
      on the pH of the solutions from which the LbL films were deposited, while the
      effects of pH were negligibly small for the PDDA-based films due to the pH
      independent positive charges on the PDDA chains. The cyclic voltammograms (CVs)
      of [Fe(CN)6]3- ions on the LbL film-coated electrodes revealed that all the LbL
      films tested are permeable to [Fe(CN)6]3- ions and that the redox reactions of
      [Fe(CN)6]3- ions proceed smoothly in the LbL polysaccharide films. It was found
      that [Fe(CN)6]3- ions are concentrated in the films from the bulk solution,
      depending on the pH of the medium and on the type of polycations in the film. The
      PEI-based films concentrated [Fe(CN)6]3- ions more effectively in an acidic
      solution than in neutral and basic media, while the pH effect was not observed
      for the PDDA-based films. In addition, we found that the [Fe(CN)6]3- ions are
      confined in the LbL films due to a strong binding of the ions to the positively
      charged sites arising from the protonated amino groups in the films. The confined
      [Fe(CN)6]3- ions exhibited redox reactions in the films, with the redox
      potentials being shifted to the positive or negative direction in the PEI- or
      PDDA-based film, respectively, as compared to the redox potential of diffusing
      [Fe(CN)6]3- ions. Thus, significant effects of the type of polycation in the LbL
      films on the redox reactions of [Fe(CN)6]3- ions were observed.

PMID- 17503860
TI  - Pore size tailoring in large-pore SBA-15 silica synthesized in the presence of
      hexane.
AB  - Large-pore SBA-15 silicas were synthesized using poly(ethylene oxide)
      poly(propylene oxide)-poly(ethylene oxide) block copolymer Pluronic P123 as a
      template and hexane as a micelle expander. The reaction was initially carried out
      at 15 degrees C, followed by the heating of the synthesis gel at temperatures
      from 40 to 130 degrees C. Small-angle X-ray scattering data indicate that highly
      ordered two-dimensional hexagonal material (SBA-15 structure) formed at 15
      degrees C and was preserved even after 5 days of heating at 130 degrees C. The
      unit-cell parameter for as-synthesized SBA-15 silicas was about 16.5 nm and
      increased only slightly after the heat treatment, whereas the unit-cell parameter
      after calcination was appreciably larger (16 vs 14 nm) for materials that were
      subjected to the thermal treatment. The pore size distribution of SBA-15 formed
      at 15 degrees C was narrow and centered at approximately 9.5 nm, which is close
      to the upper limit of pore diameters typically reported for SBA-15. The presence
      of constrictions in the pores of this material was evident. The heat treatment
      led to the elimination of the constrictions and to the pore diameter increase to
      15 nm or more, tailored by the selection of appropriate treatment temperature and
      time. The pore size increase was the fastest during the first day of treatment,
      but it continued for at least 5 days. The pore size distribution broadened as the
      time of the treatment increased beyond 1 day. The pore size increase appears to
      be primarily related to the decrease in the degree of shrinkage during the
      calcination (removal of the template) and the decrease in the pore wall
      thickness.

PMID- 17503861
TI  - Structured assemblies of ferromagnetic particles through covalent immobilization
      on functionalized polymer surfaces obtained by surface segregation.
AB  - We report a strategy to immobilize magnetic particles on polymer surfaces in an
      organized manner. Surface segregation of binary polymer blends provided surfaces
      with the desired chemical functions (carboxylic functions). These functional
      groups were demonstrated to be accessible and were thus able to react with
      magnetic particles functionalized with amine functions. The presence of a
      magnetic field during the covalent attachment step in direct surface patterning
      produced particle chains oriented parallel to the field.

PMID- 17503862
TI  - Calculations of and evidence for chain packing stress in inverse lyotropic
      bicontinuous cubic phases.
AB  - Inverse bicontinuous cubic lyotropic phases are a complex solution to the dilemma
      faced by all self-assembled water-amphiphile systems: how to satisfy the
      incompatible requirements for uniform interfacial curvature and uniform molecular
      packing. The solution reached in this case is for the water-amphiphile interfaces
      to deform hyperbolically onto triply periodic minimal surfaces. We have
      previously suggested that although the molecular packing in these structures is
      rather uniform the relative phase behavior of the gyroid, double diamond, and
      primitive inverse bicontinuous cubic phases can be understood in terms of subtle
      differences in packing frustration. In this work, we have calculated the packing
      frustration for these cubics under the constraint that their interfaces have
      constant mean curvature. We find that the relative packing stress does indeed
      differ between phases. The gyroid cubic has the least packing stress, and at low
      water volume fraction, the primitive cubic has the greatest packing stress.
      However, at very high water volume fraction, the double diamond cubic becomes the
      structure with the greatest packing stress. We have tested the model in two ways.
      For a system with a double diamond cubic phase in excess water, the addition of a
      hydrophobe may release packing frustration and preferentially stabilize the
      primitive cubic, since this has previously been shown to have lower curvature
      elastic energy. We have confirmed this prediction by adding the long chain alkane
      tricosane to 1-monoolein in excess water. The model also predicts that if one
      were able to hydrate the double diamond cubic to high water volume fractions, one
      should destabilize the phase with respect to the primitive cubic. We have found
      that such highly swollen metastable bicontinuous cubic phases can be formed
      within onion vesicles. Data from monoelaidin in excess water display a well
      defined transition, with the primitive cubic appearing above a water volume
      fraction of 0.75. Both of these results lend support to the proposition that
      differences in the packing frustration between inverse bicontinuous cubic phases
      play a pivotal role in their relative phase stability.

PMID- 17503863
TI  - Surface and interfacial segregation in blends of polystyrene with functional end
      groups and deuterated polystyrene.
AB  - The effect of chain-end chemistry on surface and interfacial segregation in
      symmetric blends of polystyrene (hPS)/deuterated polystyrene (dPS) has been
      investigated by X-ray photoelectron and secondary ion mass spectroscopy in
      conjunction with neutron reflectivity measurements. Alpha,omega-fluoroalkyl- and
      alpha,omega-carboxy-terminated polystyrenes (alpha,omega-hPS(Rf)2 and alpha,omega
      hPS(COOH)2) were used as end-functionalized polymers; the former possesses chain
      ends with lower surface energies, and the latter possesses higher surface
      energies compared with that of the main chain. In the case of an alpha,omega
      hPS(Rf)2/dPS blend film, alpha,omega-hPS(Rf)2 was enriched at the surface owing
      to the surface localization of the Rf groups, although the surface energy of the
      hPS segments was slightly higher than that of the dPS ones. On the contrary, in
      the case of an alpha,omega-hPS(COOH)2/dPS blend film, dPS was preferentially
      segregated at the surface. This may be due to a surface depletion of COOH ends
      and an apparent molecular weight increase of alpha,omega-hPS(COOH)2 produced by a
      hydrogen-bonded intermolecular association of COOH ends in addition to the
      surface energy difference between hPS and dPS segments. Interestingly, both Rf
      and COOH chain ends were partitioned to the substrate interface for the
      alpha,omega-hPS(Rf)2/dPS and alpha,omega-hPS(COOH)2/dPS blend films, resulting in
      the segregation of the hPS component at the substrate interface for both blends.
      The results presented imply that surface and interfacial segregation in polymer
      blends could be regulated by incorporating functional groups into the end
      portions of one component.

PMID- 17503864
TI  - Renewable dehydrogenase-based interfaces for bioelectronic applications.
AB  - Bioelectronic interfaces that establish electrical communication between redox
      enzymes and electrodes have potential applications as biosensors, biocatalytic
      reactors, and biological fuel cells. However, these interfaces contain labile
      components, including enzymes and cofactors, which have limited lifetimes and
      must be replaced periodically to allow long-term operation. Current methods to
      fabricate bioelectronic interfaces do not allow facile replacement of these
      components, thus limiting the useful lifetime of the interfaces. In this paper we
      describe a versatile new fabrication approach that binds the enzymes and
      cofactors using reversible ionic interactions. This approach allows the interface
      to be removed via a simple pH change and then replaced to fully regenerate the
      biocatalytic activity. The positively charged polyelectrolyte poly(ethylenimine)
      was used to ionically bond a dehydrogenase enzyme and its cofactor to a gold
      electrode that was functionalized with 3-mercaptopropionic acid and the electron
      mediator toluidine blue O. By reducing the pH, the surface-bound 3
      mercaptopropionic acid was protonated, disrupting the ionic bonds and releasing
      the enzyme-modified polyelectrolyte. After neutralization, fresh enzyme and
      cofactor were bound, regenerating the bioelectronic interface. Cyclic
      voltammetry, chronoamperometry, constant potential amperometry, electrochemical
      impedance spectroscopy, and Fourier transform infrared spectroscopy analyses were
      used to characterize the bioelectronic interfaces. For the two enzymes tested
      (secondary alcohol dehydrogenase and sorbitol dehydrogenase) and their respective
      cofactors (beta-nicotinamide adenine dinucleotide phosphate and beta-nicotinamide
      adenine dinucleotide), the reconstituted interface exhibited a surface coverage,
      an electron-transfer coefficient, and a turnover rate similar to those of the
      original interface.

PMID- 17503865
TI  - Characterization by optical measurements of the effects of some stages of
      champagne technology on the adsorption layer formed at the gas/wine interface.
AB  - This study analyzes the effects of some important factors of champagne technology
      on the ellipticity and Brewster angle microscopy (BAM) of the air/champagne
      interface in view of using the optical properties of the adsorption layer of base
      wine to forecast the stability of the champagne bubble collar. Using standard,
      ultrafiltered, and ultraconcentrated wines it was observed that champagne can
      lose amphiphilic macromolecules which adsorb on the inner glass wall of the
      bottle during storage, particles such as dead yeasts can adhere to the adsorption
      layer, a weak increase of the ethanol content during bottle fermentation can
      reduce significantly the ellipticity of the adsorption layer, and CO2 has no
      significant effect on the properties of that layer. Surprisingly, no visible
      differences of the adsorption layer were noticed between the experimental
      champagnes of the 2004 vintage of three vine varieties (Chardonnay, Pinot noir,
      and Pinot meunier). From analysis of all samples it is proposed that the mean
      value and standard deviation of the ellipticity measured during 30 min after
      pouring the wine in a Petri dish are physical quantities which satisfactorily
      characterize the adsorption layer of champagne. When needed, further
      characterization of the adsorption layer may be obtained by a detailed analysis
      of the kinetics of ellipticity during the same period and inspection of the BAM
      images of the interface.

PMID- 17503866
TI  - Direct observation of protein motion during the photochemical reaction cycle of
      bacteriorhodopsin.
AB  - Platinum-coated, conductive atomic force microscope cantilevers were used to
      deposit electrophoretically purple membranes from Halobacterium salinarum on the
      bottom part of the cantilevers. By illuminating the bacteriorhodopsin-containing
      purple membranes, the protein goes through its photochemical reaction cycle,
      during which a conformational change happens in the protein, changing its shape
      and size. The size change of the protein acts upon the cantilever by causing its
      deflection, which can be monitored by the detection system of the atomic force
      microscope. The shape of the signal, the action spectrum of the deflection
      amplitude, and the blue light inhibition of the deflection all prove that the
      origin of the signal is the conformational change arising in the
      bacteriorhodopsin during the photocycle. From the size of the signal, the
      magnitude of the protein motion could be estimated. Using polarized light, the
      orientation of the motion was determined, relative to the transition moment of
      the retinal.

PMID- 17503867
TI  - Photosensitization of ZnO nanowires with CdSe quantum dots for photovoltaic
      devices.
AB  - We combine CdSe semiconductor nanocrystals (or quantum dots) and single-crystal
      ZnO nanowires to demonstrate a new type of quantum-dot-sensitized solar cell. An
      array of ZnO nanowires was grown vertically from a fluorine-doped tin oxide
      conducting substrate. CdSe quantum dots, capped with mercaptopropionic acid, were
      attached to the surface of the nanowires. When illuminated with visible light,
      the excited CdSe quantum dots injected electrons across the quantum dot-nanowire
      interface. The morphology of the nanowires then provided the photoinjected
      electrons with a direct electrical pathway to the photoanode. With a liquid
      electrolyte as the hole transport medium, quantum-dot-sensitized nanowire solar
      cells exhibited short-circuit currents ranging from 1 to 2 mA/cm2 and open
      circuit voltages of 0.5-0.6 V when illuminated with 100 mW/cm2 simulated AM1.5
      spectrum. Internal quantum efficiencies as high as 50-60% were also obtained.

PMID- 17503868
TI  - Chemically modified solid-state nanopores.
AB  - Nanopores are extremely sensitive single-molecule sensors. Recently, electron
      beams have been used to fabricate synthetic nanopores in thin solid-state
      membranes with subnanometer resolution. Here we report a new class of chemically
      modified nanopore sensors. We describe two approaches for monolayer coating of
      nanopores: (1) self-assembly from solution, in which nanopores approximately 10
      nm diameter can be reproducibly coated, and (2) self-assembly under voltage
      driven electrolyte flow, in which we are able to coat 5 nm nanopores. We present
      an extensive characterization of coated nanopores, their stability, reactivity,
      and pH response.

PMID- 17503869
TI  - Diameter-dependent elastic modulus supports the metastable-catalyst growth of
      carbon nanotubes.
AB  - We measured the elastic modulus of individual multiwalled carbon nanotubes
      (MWCNTs) grown by catalytic chemical vapor deposition (CVD) over a broad diameter
      range (10-25 nm). Alternating current (ac) dielectrophoresis was used for
      efficient tube deposition, and atomic force microscope (AFM) force-displacement
      curve technique was used for stiffness measurements. The elastic modulus exhibits
      a strong diameter dependence, showing a difference of nearly 2 orders of
      magnitude in the 10-20 nm diameter range (thinner MWCNTs have higher elastic
      modulus). Our results support the metastable-catalyst model in which the
      catalyst's molten skin plays a key role.

PMID- 17503870
TI  - Nanosize and vitality: TiO2 nanotube diameter directs cell fate.
AB  - We generated, on titanium surfaces, self-assembled layers of vertically oriented
      TiO2 nanotubes with defined diameters between 15 and 100 nm and show that
      adhesion, spreading, growth, and differentiation of mesenchymal stem cells are
      critically dependent on the tube diameter. A spacing less than 30 nm with a
      maximum at 15 nm provided an effective length scale for accelerated integrin
      clustering/focal contact formation and strongly enhances cellular activities
      compared to smooth TiO2 surfaces. Cell adhesion and spreading were severely
      impaired on nanotube layers with a tube diameter larger than 50 nm, resulting in
      dramatically reduced cellular activity and a high extent of programmed cell
      death. Thus, on a TiO2 nanotube surface, a lateral spacing geometry with openings
      of 30-50 nm represents a critical borderline for cell fate.

PMID- 17503871
TI  - Disassembly of nanodiscs with cholate.
AB  - Nanodiscs are protein-lipid particles that furnish a nanometer-sized membrane
      environment for the investigation of membrane proteins. Nanodiscs assemble
      spontaneously upon the removal of cholate from an initial mixture of cholate,
      lipids, and engineered amphipathic proteins. A combined experimental
      computational approach is applied here to study the disassembly of nanodiscs
      through the addition of cholate to preformed particles. For this purpose, small
      angle X-ray scattering experiments and coarse-grained molecular dynamics
      simulations were performed and compared. The study offers a detailed view of
      nanodisc dynamics.

PMID- 17503872
TI  - Pulsed-interleaved excitation FRET measurements on single duplex DNA molecules
      inside C-shaped nanoapertures.
AB  - Single-molecule fluorescence resonant energy transfer (FRET) is a widely accepted
      method for determining the spatial separation between molecules. In combination
      with pulsed interleaved excitation (PIE), additional information about the
      stoichiometry of molecular interactions is obtained. PIE-FRET, however, as
      implemented with standard confocal optics, requires the dilution of the sample to
      biologically low concentrations. Here, we show that PIE-FRET measurements inside
      nanometer-sized apertures yield meaningful biochemical data at 1000 x higher
      concentrations.

PMID- 17503873
TI  - The evidence for chronic traumatic encephalopathy in boxing.
AB  - The sport of boxing has been the source of much debate, with concerns about the
      neurological risks of participating having led to many calls to ban the sport.
      This review seeks to establish an evidence base for the development of boxing
      related chronic traumatic encephalopathy (CTE) and to determine the relevance of
      this information to the modern day sport.The clinical features of CTE include
      various symptoms affecting the pyramidal and extrapyramidal systems, which
      manifest most often as disturbed gait and coordination, slurred speech and
      tremors, as well as cerebral dysfunction causing cognitive impairments and
      neurobehavioural disturbances. Both amateur and professional boxers are
      potentially at risk of developing CTE. No current epidemiological evidence exists
      to determine the prevalence of this condition in modern day boxing, despite 17%
      of professional boxers in Britain with careers in the 1930-50s having clinical
      evidence of CTE. As medical presence within the sport increases and with modern
      boxers likely to have shorter careers, a reduced exposure to repetitive head
      trauma, and improved treatment and understanding of the development of CTE will
      occur. This should lead to the incidence of CTE diminishing in boxing
      populations.

PMID- 17503874
TI  - Psychobiological mechanisms of exercise dependence.
AB  - Exercise dependence (ED) is characterised by an obsessive and unhealthy
      preoccupation with exercise. Previous research has focused largely on identifying
      behavioural aspects of ED, although the biological mechanisms remain unknown and
      are under researched. We review various ED hypotheses including affect
      regulation, anorexia analogue, sympathetic arousal and beta-endorphin. We also
      present a novel hypothesis pertaining to ED and interleukin (IL)-6, which
      combines previous hypotheses with literature from the field of psycho
      neuroimmunology. We explore the notion that IL-6 provides a link from the
      periphery to the brain, which may mediate the underlying features of ED. We
      propose a conceptual model indicating that, in individuals prone to ED, exercise
      results in a transient reduction in negative affect, but concurrently results in
      excessive production of IL-6 and the activation of neuroendocrine pathways, which
      are associated with behavioural and psychological disturbances of exercise
      withdrawal. Our intention is for this model to serve as a basis for further
      research in the area of ED, which may eventually lead to the development of
      successful treatment strategies. Recent developments in methods to reliably
      assess these biological markers from blood and saliva samples should encourage
      such research to be undertaken in exercise settings.

PMID- 17503875
TI  - Downhill ski injuries in children and adolescents.
AB  - Downhill skiing is considered to be an enjoyable activity for children and
      adolescents, but it is not without its risks and injuries. Injury rates now range
      between 3.9 and 9.1 injuries per 1000 skier days, and there has been a well
      documented increase in the number of trauma cases and fatalities associated with
      this sport. Head and neck injuries are considered the primary cause of fatal
      injuries and constitute 11-20% of total injuries among children and adolescents.
      Cranial trauma is responsible for up to 54% of total hospital injuries and 67% of
      all fatalities, whereas thoracoabdominal and spine injuries comprise 4-10% of
      fatalities. Furthermore, there has been an increase in the proportion of upper
      extremity trauma with acromioclavicular dislocations, and clavicle and humeral
      fractures accounting for the majority (22-79%) of the injuries. However, the most
      common and potentially serious injuries in children and adolescents are those to
      the lower extremity, with knee sprains and anterior cruciate ligament tears
      accounting for up to 47.7% of total injuries. Knee sprains and grade III ligament
      trauma associated with lower leg fractures account for 39-77% of ski injuries in
      this young population. Approximately 15% of downhill skiing injuries among
      children and adolescents are caused by musculoskeletal immaturity. Other factors
      include excessive fatigue, age, level of experience, and inappropriate or
      improperly adjusted equipment. Collisions and falls constitute a significant
      portion (up to 76%) of trauma, and are commonly associated with excessive speed,
      adverse slope conditions, overconfidence leading to carelessness, and behavioural
      patterns within and among gender. The type and severity of injuries are typically
      functions of biomechanical efficiency, skiing velocity or slope conditions;
      however, a multiplicative array of intrinsic and extrinsic factors may
      simultaneously be involved. Despite extensive efforts to provide a comprehensive
      picture of the aetiology of injury, limitations have hampered reporting. These
      limitations include age and injury awareness, data collection challenges, lack of
      uniformity in the definition or delineation of age classification and lack of
      knowledge of predisposing factors prior to injury. Since skill level is the
      primary impetus in minimising ski injuries, formal instruction focusing on
      strategies such as collision avoidance and helmet use, fall training minimising
      lower extremity trauma, altering ski technique and avoiding behaviours that lead
      to excessive risk are, therefore, highly recommended. Skiing equipment should be
      outfitted to match the young skier's height, weight, level of experience, boot
      size and slope conditions. Additionally, particular attention should be paid to
      slope management (i.e. overcrowding, trail and obstacle marker upkeep) and
      minimising any opportunity for excessive speed where children are present.
      Whether increases in knowledge, education and technology will reduce
      predisposition to injury among this population remains to be seen. As with all
      high-risk sports, the answer may lie in increased wisdom and responsibility of
      both the skier and the parent to ensure an adequate level of ability, self
      control and simply common sense as they venture out on the slopes.

PMID- 17503877
TI  - The role of nutritional supplements in the prevention and treatment of resistance
      exercise-induced skeletal muscle injury.
AB  - The topic of exercise-induced skeletal muscle injury has received considerable
      attention in recent years. Likewise, strategies to minimise the injury resulting
      from heavy resistance exercise have been studied. Over the past 15 years, several
      investigations have been performed focused on the role of nutritional supplements
      to attenuate signs and symptoms of muscle injury. Of these, some have reported
      favourable results, while many others have reported no benefit of the selected
      nutrient. Despite these mixed findings, recommendations for the use of
      nutritional supplements for the purposes of attenuating muscle injury are rampant
      within the popular fitness media and athletic world, largely without scientific
      support. Those nutrients include the antioxidant vitamin C (ascorbic acid) and
      vitamin E (tocopherol), N-acetyl-cysteine, flavonoids, L-carnitine, astaxanthin,
      beta-hydroxy-beta-methylbutyrate, creatine monohydrate, essential fatty acids,
      branched-chain amino acids, bromelain, proteins and carbohydrates. A discussion
      of all published peer-reviewed articles in reference to these nutrients and their
      impact on resistance exercise-induced skeletal muscle injury is presented, in
      addition to a brief view into the potential mechanism of action for each
      nutrient.Based on the current state of knowledge, the following conclusions can
      be made with regard to nutritional supplements and their role in attenuating
      signs and symptoms of skeletal muscle injury occurring as a consequence of heavy
      resistance exercise: (i) there appears to be a potential role for certain
      supplements (vitamin C, vitamin E, flavonoids, and L-carnitine); (ii) these
      supplements cannot effectively eliminate muscle injury, only attenuate certain
      signs and symptoms; (iii) it is presently unclear what the optimal dosage of
      these nutrients is (whether used alone or in combination); (iv) it is unclear
      what the optimal pretreatment period is; and (v) the effectiveness is largely
      specific to non-resistance trained individuals.Ultimately, because so few studies
      have been conducted in this area, it is difficult to recommend with confidence
      the use of selected nutrients for the sole purpose of minimising signs and
      symptoms of resistance exercise-induced muscle injury, in particular with regard
      to resistance-trained individuals.

PMID- 17503876
TI  - New modalities of pulmonary rehabilitation in patients with chronic obstructive
      pulmonary disease.
AB  - Pulmonary rehabilitation has been shown to be an important part of the management
      of patients with chronic obstructive pulmonary disease (COPD). Exercise training
      is the corner stone of a comprehensive, multidisciplinary pulmonary
      rehabilitation in COPD and has been shown to improve health-related quality of
      life and exercise capacity. Nevertheless, not every COPD patient responds well to
      pulmonary rehabilitation. Future trials should focus on new additions to
      conventional pulmonary rehabilitation programmes to optimise its effects on
      health-related quality of life, exercise capacity, body composition and muscle
      function in patients with COPD. Therefore, a patient-tailored approach is
      inevitable. Advantages and disadvantages of new modalities of pulmonary
      rehabilitation will be outlined in detail, including the following: endurance
      training and long-acting bronchodilatators; endurance training and technical
      modalities (inspiratory pressure support and inspiratory muscle training);
      interval training; resistance training; transcutaneous neuromuscular electrical
      stimulation; and exercise training and supplements (oxygen, oral creatine,
      anabolic steroids and polyunsaturated fatty acids). Based on well defined
      baseline characteristics, patients should most probably be individually selected.
      At present, these new modalities of pulmonary rehabilitation have been shown to
      improve body composition, skeletal muscle function and sometimes also exercise
      capacity. However, the translation to an improved health-related quality of life
      is mostly lacking, and cost effectiveness and long-term effects have not been
      studied. Moreover, future trials should study the effects of pulmonary
      rehabilitation in elderly patients with restrictive pulmonary diseases.

PMID- 17503879
TI  - Relationship between balance ability, training and sports injury risk.
AB  - Traditionally, balance training has been used as part of the rehabilitation
      programme for ankle injuries. More recently, balance training has been adopted to
      try and prevent injuries to the ankle and knee joints during sport. The purpose
      of this review is to synthesise current knowledge in the area of balance ability,
      training and injury risk, highlight the findings and identify any future research
      needs. A number of studies have found that poor balance ability is significantly
      related to an increased risk of ankle injuries in different activities. This
      relationship appears to be more common in males than females. Multifaceted
      intervention studies that have included balance training along with jumping,
      landing and agility exercises have resulted in a significant decrease in ankle or
      knee injuries in team handball, volleyball and recreational athletes. It is
      unknown which component of the multifaceted intervention was most effective and
      whether the effects are additive. As a single intervention, balance training has
      been shown to significantly reduce the recurrence of ankle ligament injuries in
      soccer, volleyball and recreational athletes; however, it has not been clearly
      shown to reduce ankle injuries in athletes without a prior ankle injury. Balance
      training on its own has also been shown to significantly reduce anterior cruciate
      ligament injuries in male soccer players. Surprisingly, it was also found to be
      significantly associated with an increased risk of major knee injuries in female
      soccer players and overuse knee injuries in male and female volleyball players.
      The studies with the contrasting findings differed in aspects of their balance
      training programmes. It would appear that balance training, as a single
      intervention, is not as effective as when it is part of a multifaceted
      intervention. Research is required to determine the relative contribution of
      balance training to a multifaceted intervention so as to generate an effective
      and efficient preventative programme that can be adopted by athletes of most
      levels.

PMID- 17503878
TI  - The contribution of physical activity and sedentary behaviours to the growth and
      development of children and adolescents: implications for overweight and obesity.
AB  - The obesity epidemic is a global trend and is of particular concern in children.
      Recent reports have highlighted the severity of obesity in children by
      suggesting: "today's generation of children will be the first for over a century
      for whom life expectancy falls." This review assesses the evidence that
      identifies the important role of physical activity in the growth, development and
      physical health of young people, owing to its numerous physical and psychological
      health benefits. Key issues, such as "does a sedentary lifestyle automatically
      lead to obesity" and "are levels of physical activity in today's children less
      than physical activity levels in children from previous generations?", are also
      discussed.Today's environment enforces an inactive lifestyle that is likely to
      contribute to a positive energy balance and childhood obesity. Whether a child or
      adolescent, the evidence is conclusive that physical activity is conducive to a
      healthy lifestyle and prevention of disease. Habitual physical activity
      established during the early years may provide the greatest likelihood of impact
      on mortality and longevity. It is evident that environmental factors need to
      change if physical activity strategies are to have a significant impact on
      increasing habitual physical activity levels in children and adolescents. There
      is also a need for more evidence-based physical activity guidelines for children
      of all ages. Efforts should be concentrated on facilitating an active lifestyle
      for children in an attempt to put a stop to the increasing prevalence of obese
      children.

PMID- 17503880
TI  - The next generation of drug-eluting stents: what's on the horizon?
AB  - Drug-eluting stents have radically changed the way we treat coronary artery
      disease. They offer lower restenotic rates compared with the bare metal stents
      and this enables more challenging and complex lesions to be treated. However,
      there are still limitations as restenosis has not been completely abolished and
      there are concerns about stent thrombosis. The next generation stents offer the
      technology to address these pertinent issues. This review examines the new
      analogs of the sirolimus family and their use in novel stent platforms, including
      the use of biodegradable and bioabsorbable materials employed in both stents and
      on the polymer. "Reservoir stents" that are specially designed to contain layers
      of drugs in pockets with different release profiles are discussed and an insight
      into the emerging field of bioengineered stents is highlighted.

PMID- 17503881
TI  - Evidence-based medical therapy of patients with acute coronary syndromes.
AB  - Acute coronary syndromes (ACS) present a major health challenge in modern
      medicine. With new clinical trials being conducted, our knowledge of latest
      therapies for ACS continually evolves. In this article, we review currently
      available medical therapies and provide evidence-based rationale for current
      pharmacologic therapies. Among the antiplatelet therapies, aspirin, clopidogrel,
      and glycoprotein IIb/IIIa inhibitors demonstrate significant efficacy in reducing
      morbidity and mortality. Among the anticoagulants, unfractionated heparin and low
      molecular weight heparin, particularly enoxaparin sodium, remain the hallmarks of
      therapy against which newer anticoagulants are often compared. Bivalirudin has
      recently showed significant efficacy in decreasing cardiovascular events and
      mortality, but with potentially less risk of bleeding than heparin. Results of
      trials evaluating warfarin remain inconsistent regarding potential benefits.
      Finally, fondaparinux sodium, recently tested, shows promise as a powerful yet
      safe anticoagulant. Fibrinolysis is an acceptable modality for reperfusion if
      facilities equipped for primary percutaneous revascularization are not available.
      Regarding anti-ischemic therapy, beta-adrenoceptor antagonists and nitrates
      remain critical in the early management of ACS. Inhibitors of the renin
      angiotensin-aldosterone system have also shown significant reductions in the
      morbidity and mortality of patients presenting with ACS, particularly in patients
      with left ventricular dysfunction and clinical heart failure, with ACE inhibitors
      being first-line agents and angiotensin receptor antagonists being a reasonable
      substitute if ACE inhibitors are not tolerated. Among the lipid-lowering
      therapies, statins (HMG-CoA reductase inhibitors) have been documented as being
      the most well tolerated and most efficacious therapies for ACS patients and data
      exist that they should be administered early in ACS management. Studies
      evaluating combination therapy (antiplatelet drugs, beta-adrenoceptor
      antagonists, ACE inhibitors, and lipid-lowering agents) show a clear benefit in
      mortality in patients with known coronary artery disease. Efforts to improve
      these key evidence-based medical therapies are numerous and include such programs
      as the American College of Cardiology's Guidelines Applied in Practice,
      international patient registries such as the Global Registry of Acute Coronary
      Events, and studies such as CRUSADE. Finally, patients with diabetes mellitus
      pose a challenge to clinicians both in terms of their glycemic control and in
      their apparent relative resistance to antiplatelet therapy. Studies involving ACS
      patients suggest that stringent glycemic control may result in benefits in both
      morbidity and mortality.

PMID- 17503882
TI  - Cardiovascular pharmacotherapy in patients with Marfan syndrome.
AB  - The cardiovascular complications of Marfan syndrome (MFS) remain the primary
      source of morbidity and mortality in affected patients. Over the last decade, the
      underlying pathogenesis of these cardiovascular abnormalities has been the focus
      of much research. Such research has shed light on the potential role of several
      novel medical therapies and their ability to prevent cardiovascular disease
      progression. This paper summarizes the research underlying new medical therapies
      and provides a review of the scientific foundation underlying all current medical
      therapies used for prevention of cardiovascular disease in patients with MFS,
      including beta-adrenoceptor antagonists, calcium channel antagonists, ACE
      inhibitors, and angiotensin receptor antagonists.

PMID- 17503883
TI  - Potential mechanisms of benefit with thalidomide in chronic heart failure.
AB  - This review considers the recent clinical and relevant preclinical evidence that
      thalidomide may have therapeutic benefit in chronic heart failure (HF), and
      considers some of the mechanisms by which thalidomide may elicit potentially
      beneficial effects. Persistent inflammation, involving increased levels of
      inflammatory cytokines, seems to play a pathogenic role in chronic HF by
      influencing heart contractility, inducing matrix degradation and fibrosis, and
      promoting apoptosis, contributing to myocardial remodeling. On the basis of these
      issues, immunomodulating therapy has emerged as an option in the management of
      chronic HF. Failure of anti-tumor necrosis factor (TNF) therapy has lead to
      further interest in a more general immunomodulatory approach, directed against
      the imbalanced cytokine network rather than at one particular cytokine.Some
      recent studies suggest that thalidomide, a glutamic acid derivative with proposed
      antiangiogenic, anti-inflammatory, and immunomodulatory properties, should be
      added to the list of potential immunomodulating agents in chronic HF. Thus, in a
      recent double-blind, placebo-controlled study in patients with chronic HF,
      thalidomide was found to significantly improve left ventricular ejection
      fraction. Although thalidomide has been regarded as an anti-TNF drug, it was
      found to increase plasma levels of TNFalpha in a placebo-controlled study in
      patients with HF, suggesting that other mechanisms may contribute to its
      beneficial effects. Such mechanisms could involve inhibition of neutrophils,
      matrix stabilizing, and antifibrotic effects, as well as a thalidomide-mediated
      decrease in the heart rate. However, our knowledge of the mechanisms of action of
      this drug is still scarce and will have to be further examined in forthcoming
      studies. Such studies should include experiments in animal models of HF as well
      as further preclinical trials, attempting to identify the potential mechanisms by
      which thalidomide may be beneficial in human HF.

PMID- 17503884
TI  - Long-term benefit of statin therapy initiated during hospitalization for an acute
      coronary syndrome: a systematic review of randomized trials.
AB  - OBJECTIVE: This study sought to determine if the initiation of statin (HMG-CoA
      reductase inhibitor) therapy during acute coronary syndromes reduces long-term
      mortality and other adverse cardiac outcomes. BACKGROUND: Initiation of statin
      therapy during acute coronary syndromes has not been shown to reduce mortality,
      myocardial infarction or stroke within 4 months of follow-up. METHODS: Clinical
      trials that randomized patients with acute coronary syndromes to early statin
      therapy compared with less intensive lipid reduction (placebo/lower-dose
      statin/usual care), and reported long-term outcomes were included for analysis.
      RESULTS: In all, there were seven studies (L-CAD, PTT, FLORIDA, Colivicchi et
      al., PROVE-IT, ESTABLISH, and A-to-Z) with 9553 patients who started statin
      therapy within 12 days of hospital presentation. The incidence of all-cause
      mortality was 3.4% in the statin group versus 4.6% in the less intensive lipid
      reduction group over a weighted mean follow-up of 22.9 months (relative risk [RR]
      0.74; 95% CI 0.61, 0.90; p = 0.003). The number of patients needed to treat to
      prevent one death was 84 patients. Similarly, the incidence of cardiovascular
      mortality in the statin versus the less intensive lipid reduction group was 2.4%
      versus 3.3% (RR 0.74; 95% CI 0.58, 0.93; p = 0.010), unstable angina 4.1% versus
      5.0% (RR 0.81; 95% CI 0.68, 0.98; p = 0.027), revascularization 11.2% versus
      12.9% (RR 0.86; 95% CI 0.78, 0.96; p = 0.006), stroke 1.1% versus 1.2% (RR 0.90;
      95% CI 0.62, 1.30; p = 0.56), and myocardial infarction 6.6% versus 7.0% (RR
      0.94; 95% CI 0.81, 1.09; p = 0.41). CONCLUSIONS: The benefit of early initiation
      of statin therapy during acute coronary syndromes slowly accrues over time so
      that a survival advantage is seen around 24 months. Relatively few patients need
      to be treated to prevent one death over this time period. Furthermore, this
      approach significantly reduces unstable angina and the need for
      revascularization.

PMID- 17503885
TI  - Trimetazidine administration minimizes myocardial damage and improves left
      ventricular function after percutaneous coronary intervention.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate whether the
      administration of trimetazidine, a piperazine derivative, to patients before and
      after percutaneous coronary intervention (PCI) minimizes the PCI-induced
      myocardial damage and improves left ventricular function 1 and 3 months after the
      procedure. METHODS: Fifty-two patients hospitalized for acute coronary syndromes
      (ACS) were included in this study. Patients were randomized into two groups:
      group A (trimetazidine group; n = 27) and group B (placebo group; n = 25). All
      patients received conventional antianginal therapy. In addition, group A patients
      received oral trimetazidine 20 mg every 8 hours, starting 15 days before PCI and
      continuing for 3 months after the procedure. For each patient, serum troponin I
      and creatinine kinase (CK)-MB levels were measured before PCI, then at 6, 24, and
      48 hours after the procedure; a 2D cardiac echocardiogram was performed before
      PCI and at 1 and 3 months after the procedure. RESULTS: Twenty-four hours after
      PCI, troponin I levels were >1 ng/mL in 7 of 27 patients (26%) of group A and 11
      of 25 patients (44%) in group B. Fourty-eight hours after revascularization
      troponin levels remained elevated in 15% of patients in group A and in 32% of
      patients in group B. Twenty-two percent of patients in group A had CK-MB levels
      >5 ng/mL, 24 hours after PCI, compared with 40% of patients in group B; four
      patients of group A had high CK-MB levels prior to PCI procedure.
      Echocardiographic measurements before revascularization revealed that 11 of 27
      patients (40%) in group A had an ejection fraction <50% versus 8 of 24 patients
      (33%) in group B . The number of patients with an ejection fraction <50% was
      significantly reduced in group A compared with group B at 1 and 3 months after
      PCI, i.e. 11% versus 16% (p = 0.046) at 1 month and 4% versus 16% (p = 0.017) at
      3 months.A significant improvement in regional wall motion was noted after
      treatment with trimetazidine compared with placebo. One month after PCI, inferior
      left ventricular (LV) wall hypokinesia had improved in 4 of 6 trimetazidine
      recipients and in 4 of 14 placebo recipients (p = 0.014, group A vs group B).
      After 3 months inferior wall hypokinesia improved in four patients in group A
      versus six patients in group (p = 0.05). Similarly, anterior LV wall motion
      improved in 3 of 11 patients in group A and in 1 of 6 patients in group B at 1
      month. After 3 months anterior wall hypokinesia had improved in eight patients in
      group A and in two patients in group B (p = 0.04, group A vs group B).
      CONCLUSION: The metabolic agent trimetazidine appears to minimize myocardial
      reperfusion injury during PCI and improves global and regional wall motion at 1
      and 3 months after PCI. This study was limited by small patient numbers and
      further studies are necessary to evaluate exact mechanisms of action and clinical
      implications of using trimetazidine in conjunction with PCI.

PMID- 17503887
TI  - Cost of Heart Failure in Patients Receiving beta-Blockers and Angiotensin
      Converting Enzyme Inhibitors.
AB  - OBJECTIVE: Numerous studies support the benefit of beta-blockers and angiotensin
      converting enzyme inhibition (ACE-I) in the management of heart failure. However,
      the real-world cost of heart failure in patients who take these medications is
      not well documented; furthermore, it is unclear if heart failure costs remain
      significant when current, appropriately aggressive care is delivered. DESIGN:
      This study describes 1-year medical costs in patients hospitalised for heart
      failure who received these therapies, alone or in combination. METHODS: The study
      population was derived from 2.5 million patients with at least 3 years'
      continuous eligibility in Pharmetrics((R)), an integrated claims and pharmacy
      database on approximately 25 million covered lives from 40 US health plans. The
      enrolment period was from 1 January 1996 to 31 December 2000. Costs included all
      recorded payments over a 1-year period. A total of 3073 patients (age >18 years)
      hospitalised with heart failure were identified (mean [+/- SD] age 72 +/- 13
      years; 46% female). RESULTS: The 1-year cost was $US16 786 in patients who
      received neither ACE inhibitors nor beta-blockers as compared with $US19 567,
      $US22 785 and $US27 078 in patients who received ACE inhibitors, beta-blockers or
      both drugs at maximum dosage, respectively (p < 0.001) [year of costing 2000].
      Follow-up costs were substantial, representing almost twice the initial
      hospitalisation cost. Adjusted for age, sex, diabetes mellitus, coronary disease,
      hypertension and renal failure, costs remained significant in heart failure
      patients who received ACE inhibitors and/or beta-blockers. CONCLUSIONS: The 1
      year cost of therapy for patients with heart failure is substantial, and there
      remains considerable need for more effective therapy to reduce the societal
      economic burden.

PMID- 17503886
TI  - Risk reduction strategies in ischaemic stroke : the role of antiplatelet therapy.
AB  - Stroke is a common and serious disorder, and is a leading cause of disability and
      death in adults. Transient ischaemic attacks are now recognised as being common
      precursors of stroke, with a high risk of subsequent vascular events. The
      majority of strokes are ischaemic in origin, and are typically due to athero
      thrombosis/microatheromatosis involving a large or small cerebral blood vessel or
      to an embolic event. Owing to the diffuse nature of atherothrombosis, these
      patients are at risk of ischaemic events in other vascular beds. Options for
      treating patients with acute ischaemic stroke are very limited; therefore
      prevention is a key strategy for reducing the risk of recurrent stroke and other
      vascular events. Treatment of risk factors such as hypertension, diabetes
      mellitus, smoking and obesity is an important approach for stroke prevention.
      Platelets are involved in the development of thrombi and emboli, making
      antiplatelet therapy an important preventive strategy. Antiplatelet agents are
      effective in preventing recurrent ischaemic stroke and other vascular ischaemic
      events, such as myocardial infarction and vascular death. In some cases,
      anticoagulants may be effective in preventing ischaemic stroke recurrence.
      Carotid endarterectomy can reduce stroke risk in patients with moderate- or high
      grade carotid artery stenosis. Choosing the most appropriate therapy for the
      individual patient is key to optimising stroke prevention.

PMID- 17503888
TI  - Effect of betamethasone-loratadine combination therapy on severe exacerbations of
      allergic rhinitis : a randomised, controlled trial.
AB  - OBJECTIVE: Corticosteroids are effective in controlling the inflammatory
      component of allergic rhinitis; however, evidence for the clinical efficacy of
      systemic corticosteroids in this disease is sparse. It is further common practice
      to combine oral corticosteroids with antihistamines in the treatment of acute
      exacerbations of allergic rhinitis. The aim of this study was to investigate the
      effect of low-dose oral betamethasone alone and in combination with loratadine in
      a group of patients with allergic rhinitis with clinically significant
      obstruction. METHODS: In this parallel, double-blind, active controlled
      multicentre study, 299 patients with severe allergic rhinitis were randomly
      allocated to either betamethasone 1.0mg or betamethasone 1.0mg plus loratadine
      10mg or betamethasone 0.5mg plus loratadine 10mg or loratadine 10mg alone for 5-7
      days. Total symptom scores, nasal obstruction, and doctor and patient perception
      of improvement were measured as markers of disease severity. RESULTS: Although
      not statistically significant, both betamethasone 1.0mg regimens resulted in a
      total symptom score difference of at least 1 or more from loratadine (i.e. mean
      [SD] change in total symptom score of 4.10 [3.10] and 4.40 [3.62] vs 3.10 [3.30],
      respectively, for betamethasone 1.0 mg plus loratadine, betamethasone 1.0 mg and
      loratadine). All corticosteroid-containing regimens were significantly better
      than loratadine alone with regard to the patients' (p < 0.013) and doctors' (p <
      0.009) perceptions of improvement. They significantly favoured loratadine in
      combination with betamethasone over single-drug therapy (i.e. odds ratio:
      investigator ratings 0.49, 0.36 and 0.45, and patient ratings 0.47, 0.40 and
      0.43, respectively, for 0.5 mg and 1.0 mg betamethasone plus loratadine and
      betamethasone 1.0 mg alone vs loratadine alone). Betamethasone 1.0mg plus
      loratadine also resulted in significant reduction of the relapse rate compared
      with the other therapies. CONCLUSIONS: This study demonstrated the benefit of a
      short course of a systemic low dosage of corticosteroids with and without
      antihistamine therapy during acute severe exacerbations of allergic rhinitis.
      Combination treatment with betamethasone 1.0mg and loratadine 10mg was
      significantly better in relieving symptoms of hayfever as experienced by
      patients. This was the first study to give evidence of benefit of systemic low
      dose corticosteroids with and without an antihistamine in patients with acute
      exacerbations of allergic rhinitis.

PMID- 17503889
TI  - Risperidone versus Conventional Antipsychotics for Schizophrenia and
      Schizoaffective Disorder : Symptoms, Quality of Life and Resource Use under
      Customary Clinical Care.
AB  - OBJECTIVE: To prospectively compare risperidone with conventional antipsychotic
      agents among schizophrenia patients treated under usual practice conditions.
      DESIGN: One-year, multicentre, open-label, randomised trial carried out in 21
      centres in 17 states of the US. PATIENTS: 684 patients were followed from 1995 to
      1997, and must have experienced a symptom relapse at study start. INTERVENTIONS:
      Patients were randomly assigned to risperidone therapy or their physician's 'best
      choice' of any one of the 13 conventional antipsychotic medications approved in
      the US. MAIN OUTCOME MEASURES AND RESULTS: Outcomes measured were changes in
      psychiatric symptoms, side effects, satisfaction with drug therapy, quality of
      life (including health-related quality of life [HRQOL]) and resource utilisation.
      A subgroup analysis of the non-switchers was also conducted. Irrespective of
      treatment group, treatment switching and days with no drug therapy were observed.
      Compared with patients on conventional antipsychotics, those in the risperidone
      group achieved statistically superior scores on the Positive and Negative
      Syndrome Scale for Schizophrenia (PANSS) [PANSS total score improved from 83.32
      to 61.80 vs 81.42 to 66.99 in the risperidone and conventional groups,
      respectively), Barnes Akathisia Scale (scores improved from 0.89 to 0.55 vs 0.87
      to 0.81 in the risperidone and conventional groups, respectively), and 36-Item
      Short Form Health Survey (SF-36) scale (scores improved from 32.83 to 39.92 vs
      32.55 to 37.22 in the risperidone and conventional groups, respectively) during
      the 1-year treatment period. A significantly higher percentage of risperidone-
      treated patients had a 60% improvement in PANSS scores at 12 months (20.9% of
      patients compared with 10.7% in the risperidone and conventional groups,
      respectively). There was no statistically significant difference in resource
      utilisation between the two groups. Among non-switchers, patients in the
      risperidone group had lower total costs and more clinical benefits. CONCLUSIONS:
      Conditions of usual practice resulted in a high degree of non-treatment,
      treatment changing and multi-antipsychotic drug therapy. Patients in the
      risperidone group had better clinical outcomes (e.g. reduced psychiatric symptoms
      and side effects) and improved HRQOL. There were no significant differences in
      healthcare utilisation between the two study groups.

PMID- 17503890
TI  - Weight gain, improvements in metabolic profiles and immunogenicity with insulin
      or sulphonylurea administration in AIDS.

PMID- 17503891
TI  - Switch from risperidone to perospirone in patients with chronic schizophrenia.

PMID- 17503892
TI  - Toxic epidermal necrolysis induced by a triple-drug regimen for helicobacter
      pylori eradication.

PMID- 17503893
TI  - Intermittent bisphosphonate therapy in postmenopausal osteoporosis: progress to
      date.
AB  - Bisphosphonates are the most widely prescribed drugs in osteoporosis today. They
      have unequivocally shown their ability to reduce fracture rate at the spine
      (alendronic acid, risedronic acid, ibandronic acid) and at the hip (alendronic
      acid and risedronic acid). However, their dosage and administration procedures
      and the adverse reactions induced by their oral intake are responsible for low
      adherence. Therefore, intermittent regimens have been developed. Weekly
      alendronic acid and risedronic acid provide similar benefits, in terms of bone
      mineral density (BMD) and changes in biochemical markers, as those seen with
      their daily formulations. Ibandronic acid has been shown to reduce vertebral
      fractures when given intermittently. Ibandronic acid given orally monthly and
      intravenously every 2 or 3 months provides increases in BMD similar to the daily
      formulation. Yearly intravenous infusions of zoledronic acid are currently being
      evaluated for their ability to reduce fractures. If the efficacy and safety of
      bisphosphonates given at administration intervals longer than weekly are
      confirmed, this might significantly improve patient adherence and long-term
      outcomes of bisphosphonate treatment in postmenopausal osteoporosis.

PMID- 17503894
TI  - Selective estrogen receptor modulators for postmenopausal osteoporosis: current
      state of development.
AB  - Selective estrogen receptor modulators (SERMs) are structurally different
      compounds that interact with intracellular estrogen receptors in target organs as
      estrogen receptor agonists and antagonists. These drugs have been intensively
      studied over the past decade and have proven to be a highly versatile group for
      the treatment of different conditions associated with aging, including hormone
      responsive cancer and osteoporosis. Tamoxifen and toremifene are currently used
      to treat advanced breast cancer and also have beneficial effects on bone mineral
      density and serum lipids in postmenopausal women. Raloxifene is the only SERM
      approved worldwide for the prevention and treatment of postmenopausal
      osteoporosis and vertebral fractures. However, although these SERMs have many
      benefits, they may also be responsible for some potentially very serious adverse
      effects, such as thromboembolic disorders and, in the case of tamoxifen, uterine
      cancer. These adverse effects represent a major concern given that long-term
      therapy is required to prevent osteoporosis. Moreover, both preclinical and
      clinical reports suggest that tamoxifen, toremifene and raloxifene are
      considerably less potent than estrogen. The search for the 'ideal' SERM, which
      would have estrogenic effects on bone and serum lipids, neutral effects on the
      uterus, and antiestrogenic effects on breast tissue, but none of the adverse
      effects associated with current therapies, is currently under way. Ospemifene,
      lasofoxifene, bazedoxifene and arzoxifene, which are new SERM molecules with
      potential greater efficacy and potency than previous SERMs, are currently under
      investigation for use in the treatment and prevention of osteoporosis. These
      drugs have been shown to be comparably effective to conventional hormone
      replacement therapy in animal models of osteoporosis, with potential indications
      for an improved safety profile. Clinical efficacy data from ongoing phase III
      trials are awaited so that a true understanding of the therapeutic potential of
      these compounds can be obtained.

PMID- 17503895
TI  - Optimal management of asthma in elderly patients: strategies to improve adherence
      to recommended interventions.
AB  - Adherence to asthma medications presents a problem in all age groups, and older
      people with chronic illnesses such as asthma also have multiple co-morbidities
      and consequently complex healthcare needs. It has been suggested that older
      people are also less likely to adhere to medication and treatment than younger
      people. Although the prevalence of asthma in older people is similar to that of
      the general population, over two-thirds of those who die from asthma are >50
      years of age and there is strong evidence for under-diagnosis. Clinicians
      therefore face specific challenges in providing healthcare with respect to both
      asthma diagnosis and treatment in older age groups. Non-adherence to medication
      can be defined as either 'intentional' or 'unintentional'. Unintentional non
      adherence is more likely to be associated with sociodemographic or physical
      barriers to the use of medication. Intentional non-adherence results from the
      balance of individual reasoning of risks versus the benefits of taking medication
      and acceptance of asthma diagnosis. Intentional non-adherence can be addressed
      through strategies that influence health beliefs and concerns about the adverse
      effects of medicine. Unintentional adherence can be addressed by assessing and
      educating the patient in relation to device use and providing education and clear
      written instructions about medication requirements. However, some barriers to
      medication use, such as financial ones, may be systematic. Most studies of
      medication use, efficacy, adverse effects and adherence in patients with asthma
      primarily involve younger people. Studies of strategies to improve asthma
      adherence outcomes specifically in older people are urgently needed.

PMID- 17503896
TI  - Oral anticancer drugs in the elderly: an overview.
AB  - The increasing number of elderly people in the world population has led to a
      parallel increase in the number of older cancer patients, with over 45% of all
      cancers in Europe occurring in patients >70 years of age. The increasing tendency
      to use oral chemotherapy is thus of interest in the elderly, given that both
      elderly patients and their physicians prefer to use less complex and toxic
      regimens when such treatments have equivalent efficacy to more complex regimens.
      However, data from studies designed to evaluate these therapies in the elderly
      are currently limited. Factors that must be considered before prescribing oral
      agents to this subset of patients include age-related physiological changes
      affecting clinical pharmacology, adherence, the patient's capability to self
      administer medications, and safety issues concerning the older patient and his or
      her caregivers. The idea that elderly patients may benefit from the introduction
      of oral chemotherapy is very fashionable, but to date there is no proof that this
      approach is as effective as intravenous therapy in this age group, particularly
      since randomised trials are lacking. This review discusses these issues and
      reviews current information about the use of specific oral chemotherapeutic drugs
      for major neoplastic diseases in the elderly.

PMID- 17503897
TI  - Docetaxel in non-small cell lung cancer: impact on quality of life and
      pharmacoeconomics.
AB  - Lung cancer is one of the leading causes of cancer-related deaths in
      industrialised countries, with non-small cell lung cancer (NSCLC) accounting for
      the majority of cases. A large proportion of patients present with advanced
      disease and are >65 years of age at the time of diagnosis. Systemic chemotherapy
      may be offered in an effort to improve survival and quality of life (QOL).
      Chemotherapy with platinum-based compounds has been shown to modestly improve
      survival and QOL, and is considered the standard of care as first-line treatment
      in patients with a good performance status. The last decade has seen the
      emergence of newer generation chemotherapy agents for the treatment of all cancer
      types. We review the evidence for the use of docetaxel, an antimicrotubular
      agent, in patients with advanced NSCLC. In this review, we evaluate not only the
      effects of docetaxel on survival, but also its impact on QOL and economic issues.
      Docetaxel is a potent anticancer agent with activity both as a single agent or in
      combination, and is used both as a first- and second-line treatment in advanced
      NSCLC. The improvements observed in patients' QOL and the cost effectiveness of
      docetaxel make it a very reasonable choice in older patients with good
      performance status and advanced disease who are candidates for chemotherapy.

PMID- 17503899
TI  - Invited article: a [corrected] unified evaluation of iterative projection
      algorithms for phase retrieval.
AB  - Iterative projection algorithms are successfully being used as a substitute of
      lenses to recombine, numerically rather than optically, light scattered by
      illuminated objects. Images obtained computationally allow aberration-free
      diffraction-limited imaging and the possibility of using radiation for which no
      lenses exist. The challenge of this imaging technique is transferred from the
      lenses to the algorithms. We evaluate these new computational "instruments"
      developed for the phase-retrieval problem, and discuss acceleration strategies.

PMID- 17503898
TI  - Age-related differences in the prevalence of potential drug-drug interactions in
      ambulatory dyslipidaemic patients treated with statins.
AB  - BACKGROUND AND OBJECTIVE: Elderly patients may be at higher risk of drug-drug
      interactions (DDIs) because of polypharmacy. This study evaluated age-specific
      differences in the prevalence of clinically relevant potential DDIs (pDDIs) in
      ambulatory dyslipidaemic patients treated with an HMG-CoA reductase inhibitor
      (statin). We hypothesised that elderly patients are at higher risk for pDDIs
      because of the presence of more drugs and drugs with a higher potential for DDIs
      in this age group. METHODS: A total of 2742 dyslipidaemic ambulatory patients
      treated with a statin were included in this cross-sectional study. Drug treatment
      was screened for clinically relevant pDDIs using an electronic drug interaction
      program (DRUG-REAX System). RESULTS: The study sample consisted of 483 (17.6%)
      patients aged < or = 54 years, 732 (26.7%) aged 55-64 years, 924 (33.7%) aged 65
      74 years and 603 (22.0%) patients aged > or = 75 years. Patients > or =75 years
      had significantly more pharmacologically active substances prescribed than
      patients aged < or =54 years (mean 5.8 vs 3.8, respectively; p < 0.001).
      Cardiovascular diseases such as coronary heart disease, heart failure or
      arrhythmias were also significantly more prevalent in patients aged > or = 75
      years than in younger patients. The overall prevalence of pDDIs increased
      significantly from 7.9% in those aged < or = 54 years to 18.4% in patients aged >
      or = 75 years (p < 0.001). The frequency of both pDDIs associated with statins
      and non-statin pDDIs increased with age. Risk factors for pDDIs in patients aged
      > or = 75 years were arrhythmias, heart failure and the number of
      pharmacologically active substances prescribed. The more frequent prescription of
      cardiovascular drugs with a high potential for pDDIs (e.g. amiodarone and
      digoxin) in patients aged > or = 75 years was mainly responsible for the observed
      increases in statin and non-statin pDDIs in this age group. CONCLUSIONS: Compared
      with younger patients, elderly dyslipidaemic patients are at a higher risk for
      clinically relevant pDDIs, mainly because of a higher number of drugs prescribed.
      In addition, patients aged > or = 75 years were prescribed more drugs with a high
      potential for DDIs, especially drugs used for the treatment of arrhythmias and
      heart failure. The risk for adverse reactions associated with pDDIs may often be
      reduced by dose adjustment, close monitoring or selection of an alternative drug.

PMID- 17503900
TI  - The NASA Spitzer Space Telescope.
AB  - The National Aeronautics and Space Administration's Spitzer Space Telescope
      (formerly the Space Infrared Telescope Facility) is the fourth and final facility
      in the Great Observatories Program, joining Hubble Space Telescope (1990), the
      Compton Gamma-Ray Observatory (1991-2000), and the Chandra X-Ray Observatory
      (1999). Spitzer, with a sensitivity that is almost three orders of magnitude
      greater than that of any previous ground-based and space-based infrared
      observatory, is expected to revolutionize our understanding of the creation of
      the universe, the formation and evolution of primitive galaxies, the origin of
      stars and planets, and the chemical evolution of the universe. This review
      presents a brief overview of the scientific objectives and history of infrared
      astronomy. We discuss Spitzer's expected role in infrared astronomy for the new
      millennium. We describe pertinent details of the design, construction, launch, in
      orbit checkout, and operations of the observatory and summarize some science
      highlights from the first two and a half years of Spitzer operations. More
      information about Spitzer can be found at http://spitzer.caltech.edu/.

PMID- 17503901
TI  - Photonic Doppler velocimetry of laser-ablated ultrathin metals.
AB  - Obtaining velocity information from the interaction of a laser pulse on a metal
      layer provides insight into the rapid dynamics of material removal and plasma
      plume physics during ablation. A traditional approach involves using a velocity
      interferometer system for any reflector (VISAR) on a reflective metal surface.
      However, when the target is a thin metal layer, the cohesion of the surface is
      quickly lost resulting in a large spread of particle velocities that cannot be
      easily resolved by VISAR. This is due to material ejection"confusing" the VISAR
      measurement surface, effectively washing out the spatial fringe visibility in the
      VISAR interferometer. A new heterodyne-based optical velocimeter method is the
      photonic Doppler velocimeter (PDV). Because PDV tracks motion in a frequency
      encoded temporal electro-optical signal, velocity information is preserved and
      allows for multiple velocity components to be recorded simultaneously. The
      challenge lies in extracting PDV velocity information at short (nanosecond) laser
      ablation time scales with rapidly varying heterodyne beats by using electronic,
      optical, and analytical techniques to recover the velocity information from a
      fleeting signal. Here we show how we have been able to obtain velocity
      information on the nanosecond time scale and are able to compare it to
      hydrodynamic simulations. Also, we examine refinements to our PDV system by
      increasing the bandwidth, utilizing different probes, and sampling different
      analysis techniques.

PMID- 17503902
TI  - Large atom number Bose-Einstein condensate of sodium.
AB  - We describe the setup to create a large Bose-Einstein condensate containing more
      than 120 x 10(6) atoms. In the experiment a thermal beam is slowed by a Zeeman
      slower and captured in a dark-spot magneto-optical trap (MOT). A typical dark
      spot MOT in our experiments contains 2.0 x 10(10) atoms with a temperature of 320
      microK and a density of about 1.0 x 10(11) atoms/cm(3). The sample is spin
      polarized in a high magnetic field before the atoms are loaded in the magnetic
      trap. Spin polarizing in a high magnetic field results in an increase in the
      transfer efficiency by a factor of 2 compared to experiments without spin
      polarizing. In the magnetic trap the cloud is cooled to degeneracy in 50 s by
      evaporative cooling. To suppress the three-body losses at the end of the
      evaporation, the magnetic trap is decompressed in the axial direction.

PMID- 17503903
TI  - High throughput spectrometer for fast localized Doppler measurements.
AB  - A new custom-built duo spectrometer has been commissioned for fast localized
      Doppler measurements of plasma ions in the Madison Symmetric Torus. The
      instrument combines very high optical throughput (transmission efficiency of 6%
      and etendue of 0.80 mm(2) sr divided into two simultaneous measurements) with
      good resolution (lambda/Deltalambda=5600). The design is a double grating variant
      of the Czerny-Turner layout and has been carefully optimized for fast (100 kHz)
      measurements of the C VI line at 343.4 nm. The instrument is currently being
      applied for high speed charge exchange recombination spectroscopy measurements.

PMID- 17503904
TI  - Reflection of attosecond x-ray free electron laser pulses.
AB  - In order to utilize hard x-ray free electron lasers (XFEL's) when they are
      extended to attosecond pulse lengths, it is necessary to choose optical elements
      with minimal response time. Specular grazing-incidence optics made of low-Z
      materials are popular candidates for reflectors since they are likely to
      withstand x-ray damage and provide sufficiently large reflectivities. Using
      linear-optics reflection theory, we calculated the transient reflectivity of a
      delta-function electric pulse from a homogenous semi-infinite medium as a
      function of angle of incidence for s- and p-polarized light. We specifically
      considered the pulse response of beryllium, diamond, silicon carbide, and
      silicon, all of which are of relevance to the XFEL's that are currently being
      built. We found that the media emit energy in a damped oscillatory way, and that
      the impulse-response times are shorter than 0.3 fs for normal incidence. For
      grazing incidence, the impulse-response time is substantially shorter, making
      grazing-incidence mirrors a good choice for deep subfemtosecond reflective
      optics.

PMID- 17503905
TI  - Mode-locking optimization with a real-time feedback system in a Nd:yttrium
      lithium fluoride laser cavity.
AB  - We present a control system, which allows an automatic optimization of the pulse
      train stability in a mode-locked laser cavity. In order to obtain real-time
      corrections, we chose a closed loop approach. The control variable is the cavity
      length, mechanically adjusted by gear system acting on the rear cavity mirror,
      and the controlled variable is the envelope modulation of the mode-locked pulse
      train. Such automatic control system maintains the amplitude of the mode-locking
      pulse train stable within a few percent rms during the working time of the laser.
      Full implementation of the system on an Nd:yttrium lithium fluoride actively mode
      locked laser is presented.

PMID- 17503906
TI  - Discrete retardance second harmonic generation ellipsometry.
AB  - A new instrument was constructed to perform discrete retardance nonlinear optical
      ellipsometry (DR-NOE). The focus of the design was to perform second harmonic
      generation NOE while maximizing sample and application flexibility and minimizing
      data acquisition time. The discrete retardance configuration results in
      relatively simple computational algorithms for performing nonlinear optical
      ellipsometric analysis. NOE analysis of a disperse red 19 monolayer yielded
      results that were consistent with previously reported values for the same surface
      system, but with significantly reduced acquisition times.

PMID- 17503907
TI  - Stable, mode-matched, medium-finesse optical cavity incorporating a
      microcantilever mirror: optical characterization and laser cooling.
AB  - A stable optical resonator has been built using a 30-microm-wide, metal-coated
      microcantilever as one mirror. The second mirror was a 12.7-mm-diameter concave
      dielectric mirror. By positioning the two mirrors 75 mm apart in a near
      hemispherical configuration, a Fabry-Perot cavity with a finesse equal to 55 was
      achieved. The finesse was limited by the optical loss in the cantilever's metal
      coating; diffraction losses from the small mirror were negligible. The cavity
      achieved passive laser cooling of the cantilever's Brownian motion.

PMID- 17503908
TI  - New developments for an electron impact (e,2e)(e,3e) spectrometer with multiangle
      collection and multicoincidence detection.
AB  - We describe new developments aimed to extend the capabilities and the sensitivity
      of the (e,2e)(e,3e) multicoincidence spectrometer at Orsay University [Duguet et
      al., Rev. Sci. Instrum. 69, 3524 (1998)]. The spectrometer has been improved by
      the addition of a third multiangle detection channel for the fast "scattered"
      electron. The present system is unique in that it is the only system which
      combines three toroidal analyzers all equipped with position sensitive detectors,
      thus allowing the triple coincidence detection of the three electrons present in
      the final state of an electron impact double ionization process. The setup allows
      measurement of the angular and energy distributions of the ejected electrons over
      almost the totality of the collision plane as well as that of the scattered
      electron over a large range of scattering angles in the forward direction. The
      resulting gain in sensitivity ( approximately 25) has rendered feasible a whole
      class of experiments which could not be otherwise envisaged. The setup is
      described with a special emphasis on the new toroidal analyzer, data acquisition
      hardware, and data analysis procedures. The performances are illustrated by
      selected results of (e,2e) and (e,3e) experiments on the rare gases.

PMID- 17503909
TI  - Optimized end station and operating protocols for reflection extended x-ray
      absorption fine structure (ReflEXAFS) investigations of surface structure at the
      European Synchrotron Radiation Facility beamline BM29.
AB  - The development of the capability to engineer the surface properties of materials
      to match specific requirements demands high quality surface characterization
      techniques. The ideal tool should provide chemically specific structural
      characterization as well as surface sensitivity and depth profiling. Ideally the
      characterization method should also be applicable to systems both with and
      without long range order. X-ray absorption spectroscopy fine structure, when
      using the standard transmission detection system, provides all this information
      with the significant exception of surface sensitivity. In contrast, by detecting
      the reflected instead of the transmitted beam, it encompasses all these
      requirements because when the incident beam impinges onto a sample surface at
      glancing angles, in conditions close to the total reflection, only the outermost
      regions of the system under study are sampled. Such a technique provides
      information about the local structure as a function of depth as well as thin
      layer structure in the case of layered samples. Although it is potentially the
      ideal tool to study surface modified materials, experimental difficulties have
      hampered its widespread use in the fields of surface and materials sciences. As a
      solution to the experimental challenges, we provide a detailed description of an
      appropriate experimental station, the sample requirements, the measuring
      protocols, and software routines needed to optimize the collection of the data.
      To illustrate the capabilities of the technique the results obtained for a model
      multilayer sample are presented and analyzed under the total external reflection
      approximation.

PMID- 17503910
TI  - High-temperature multipass cell for infrared spectroscopy of heated gases and
      vapors.
AB  - In absorption spectroscopy, infrared spectra of heated gases or condensed samples
      in the vapor phase are usually recorded with a single pass heated gas cell. This
      device exhibits two orders of magnitude lower sensitivity than the high
      temperature multipass cell presented in this article. Our device is a novel type
      of compact long path absorption cell that can withstand aggressive chemicals in
      addition to temperatures up to 723 K. The construction of the cell and its
      technical features are described in detail, paying special attention to the
      mechanisms that compensate for thermal expansion and that allow the user to vary
      the optical path length under any thermal or vacuum condition. The cell may be
      used with a laser source or implemented within a Fourier transform infrared
      spectrometer. Its design is compatible with optical arrangements using astigmatic
      mirrors or spherical mirrors in a Herriott configuration. Here we implement a
      homebuilt Herriott-type cell with a total optical path length of up to 35 m. In
      order to demonstrate the feasibility of the cell, methane and water vapor
      absorption lines showing dissimilar temperature effects on line intensity were
      recorded with the help of a mid-infrared laser source tunable between 3 and 4
      microm. Emphasis is put on lines that are too weak to be recorded with a single
      pass cell.

PMID- 17503911
TI  - Photoreflectance spectroscopy with a step-scan Fourier-transform infrared
      spectrometer: technique and applications.
AB  - We report on a new technique of realizing photoreflectance (PR) spectroscopy with
      a step-scan Fourier-transform infrared spectrometer. The experimental
      configuration is briefly described and a detailed theoretical analysis is
      conducted. The results reveal two distinct features of this PR technique that (i)
      the PR related signal is enhanced by a factor of at least 100 relative to those
      of the conventional PR techniques and (ii) the unwanted spurious signal
      introduced by either diffuse reflected pump beam or pump-beam induced material's
      photoluminescence reaching the photodetector of the PR configuration is
      eliminated without any special consideration of normalization for deducing the
      final PR spectrum. Applications are given as examples in the study of GaNAs/GaAs
      single quantum wells and GaInP/AlGaInP multiple quantum wells, respectively,
      under different pump-beam excitation energy and/or power. The experimental
      results approve the theoretically predicted features and illustrate the
      possibility of investigating weak PR features by using high pump-beam power. A
      brief comparison of this technique with the conventional PR techniques is given,
      and the extendibility of this technique to long-wavelength spectral regions is
      pointed out.

PMID- 17503912
TI  - Quasianamorphic optical imaging system with tomographic reconstruction for
      electron beam imaging.
AB  - We have developed a quasianamorphic optical tomography system coupled to a streak
      camera to provide continuous recording of the electron beam profile of an
      intense, long-pulse induction accelerator. A tomographic reconstruction method
      based on a maximum-entropy algorithm is used to reconstruct the images. The
      system has simplified the calculation of beam moments, eliminated ambiguity due
      to beam motion, and contributed to accelerator tuning.

PMID- 17503913
TI  - Lithium ion sources for investigations of fast ion transport in magnetized
      plasmas.
AB  - In order to study the interaction of ions of intermediate energies with plasma
      fluctuations, two plasma immersible lithium ion sources, based on solid-state
      thermionic emitters (Li aluminosilicate) were developed. Compared to discharge
      based ion sources, they are compact, have zero gas load, small energy dispersion,
      and can be operated at any angle with respect to an ambient magnetic field of up
      to 4.0 kG. Beam energies range from 400 eV to 2.0 keV with typical beam current
      densities in the 1 mAcm(2) range. Because of the low ion mass, beam velocities of
      100-300 kms are in the range of Alfven speeds in typical helium plasmas in the
      large plasma device.

PMID- 17503914
TI  - Apparatus for time-resolved and energy-resolved measurement of internal
      conversion electron emission induced by nuclear resonant excitation with
      synchrotron radiation.
AB  - A high-energy and large-object-spot type cylindrical mirror analyzer (CMA) was
      constructed with the aid of electron trajectory simulations. By adopting a
      particular shape for the outer cylinder, an energy resolution of 7% was achieved
      without guide rings as used in conventional CMAs. Combined with an avalanche
      photodiode as an electron detector, the K-shell internal conversion electrons
      were successfully measured under irradiation of synchrotron radiation at 14.4 keV
      in an energy-resolved and time-resolved manner.

PMID- 17503915
TI  - Study of saturation of CR39 nuclear track detectors at high ion fluence and of
      associated artifact patterns.
AB  - The occurrence of saturation in CR39 solid state nuclear track detectors has been
      systematically studied as a function of the incident ion (alpha particles and
      laser-accelerated protons) fluence and the etching time. When overexposed (i.e.,
      for fluences above approximately 10(8) particles/cm(2)) and/or overetched, the
      CR39 detectors enter a saturated regime where direct track counting is not
      possible anymore. In this regime, optical measurements of saturated CR39
      detectors become unreliable as well, since the optical response of the saturated
      detectors with respect to the ion fluence is highly nonlinear. This nonlinear
      optical response is likely due to scattering from the surface of irregular
      clumping patterns which have a diameter approximately 20 microm, i.e., ten times
      larger than the diameter of individual tracks. These patterns, which aggregate
      many individual tracks, are observed to develop in highly saturated regimes. For
      fluences typical of high energy short pulse laser experiments, saturation occurs,
      inducing the appearance of artifact ringlike structures. By careful microscopic
      analysis, these artifact ring patterns can be distinguished from the genuine
      rings occurring below saturation and characteristic of low energy laser
      accelerated proton beams.

PMID- 17503916
TI  - Electron gun using carbon-nanofiber field emitter.
AB  - An electron gun constructed using carbon-nanofiber (CNF) emitters and an
      electrostatic Einzel lens system has been characterized for the development of a
      high-resolution x-ray source. The CNFs used were grown on tungsten and palladium
      tips by plasma-enhanced chemical-vapor deposition. Electron beams with the
      energies of 10<E<20 keV were focused by the electrostatic lens and impinged on a
      W target for x-ray radiography. Analyzing the recorded x-ray radiographs, the
      focal spot size of the electron beam extracted from the CNFs was estimated to be
      D<50 microm in diameter. Superior performance was realized by using CNFs with
      larger fiber radii (100-500 nm) grown sparsely on the metal tips, which were
      installed in a holder at the short length L=0.5 mm.

PMID- 17503917
TI  - Wire tomography in the H-1NF heliac for investigation of fine structure of
      magnetic islands.
AB  - Electron beam wire tomography in the H-1NF heliac enables high resolution mapping
      of vacuum flux surfaces with minimal disruption of the plasma operations
      schedule. Recent experimental results have proven this technique to be a highly
      accurate and high resolution method for mapping vacuum magnetic islands. Islands
      of width as small as delta approximately 8 mm have been measured, providing
      estimates of the internal rotational transform of the island. Point-to-point
      comparison of the mapping results with computer tracing, in conjunction with an
      image warping technique, enables systematic exploration of magnetic islands and
      surfaces of interest. Recent development of a fast mapping technique
      significantly reduced the mapping time and made this technique suitable for
      mapping at higher magnetic fields. This article presents recent experimental
      results and associated techniques.

PMID- 17503918
TI  - Bipolar pulse generator for intense pulsed ion beam accelerator.
AB  - A new type of pulsed ion beam accelerator named "bipolar pulse accelerator" (BPA)
      has been proposed in order to improve the purity of intense pulsed ion beams. To
      confirm the principle of the BPA, we developed a bipolar pulse generator for the
      bipolar pulse experiment, which consists of a Marx generator and a pulse forming
      line (PFL) with a rail gap switch on its end. In this article, we report the
      first experimental result of the bipolar pulse and evaluate the electrical
      characteristics of the bipolar pulse generator. When the bipolar pulse generator
      was operated at 70% of the full charge condition of the PFL, the bipolar pulse
      with the first (-138 kV, 72 ns) and the second pulse (+130 kV, 70 ns) was
      successfully obtained. The evaluation of the electrical characteristics indicates
      that the developed generator can produce the bipolar pulse with fast rise time
      and sharp reversing time.

PMID- 17503919
TI  - Diagnosing pure-electron plasmas with internal particle flux probes.
AB  - Techniques for measuring local plasma potential, density, and temperature of pure
      electron plasmas using emissive and Langmuir probes are described. The plasma
      potential is measured as the least negative potential at which a hot tungsten
      filament emits electrons. Temperature is measured, as is commonly done in
      quasineutral plasmas, through the interpretation of a Langmuir probe current
      voltage characteristic. Due to the lack of ion-saturation current, the density
      must also be measured through the interpretation of this characteristic thereby
      greatly complicating the measurement. Measurements are further complicated by low
      densities, low cross field transport rates, and large flows typical of pure
      electron plasmas. This article describes the use of these techniques on pure
      electron plasmas in the Columbia Non-neutral Torus (CNT) stellarator. Measured
      values for present baseline experimental parameters in CNT are phi(p)=-200+/-2 V,
      T(e)=4+/-1 eV, and n(e) on the order of 10(12) m(-3) in the interior.

PMID- 17503920
TI  - A retractable electron emitter for the creation of unperturbed pure electron
      plasmas.
AB  - A retractable electron emitter has been constructed for the creation of
      unperturbed pure electron plasmas on magnetic surfaces in the Columbia Non
      neutral Torus stellarator. The previous method of electron emission using
      emitters mounted on stationary rods limited the confinement time to 20 ms. A
      pneumatically driven system that can retract from the magnetic axis to the last
      closed flux surface in less than 20 ms while filling the surfaces with electrons
      was designed. The motion of the retractable emitter was modeled with a system of
      dynamical equations. The measured position versus time of the emitter agrees well
      with the model and the fastest axis-to-edge retraction was measured to be 20 ms
      with 40 psig helium gas driving the pneumatic piston.

PMID- 17503921
TI  - New Thomson scattering diagnostic on RFX-mod.
AB  - This article describes the completely renovated Thomson scattering (TS)
      diagnostic employed in the modified Reversed Field eXperiment (RFX-mod) since it
      restarted operation in 2005. The system measures plasma electron temperature and
      density profiles along an equatorial diameter, measuring in 84 positions with 7
      mm spatial resolution. The custom built Nd:YLF laser produces a burst of 10
      pulses at 50 Hz with energy of 3 J, providing ten profile measurements in a
      plasma discharge of about 300 ms duration. An optical delay system accommodates
      three scattering volumes in each of the 28 interference filter spectrometers.
      Avalanche photodiodes detect the Thomson scattering signals and allow them to be
      recorded by means of waveform digitizers. Electron temperature is obtained using
      an alternative relative calibration method, based on the use of a supercontinuum
      light source. Rotational Raman scattering in nitrogen has supplied the absolute
      calibration for the electron density measurements. During RFX-mod experimental
      campaigns in 2005, the TS diagnostic has demonstrated its performance, routinely
      providing reliable high resolution profiles.

PMID- 17503922
TI  - Tomography experiment of an integrated circuit specimen using 3 MeV electrons in
      the transmission electron microscope.
AB  - The possibility of utilizing high-energy electron tomography to characterize the
      micron-scale three dimensional (3D) structures of integrated circuits has been
      demonstrated experimentally. First, electron transmission through a tilted SiO(2)
      film was measured with an ultrahigh-voltage electron microscope (ultra-HVEM) and
      analyzed from the point of view of elastic scattering of electrons, showing that
      linear attenuation of the logarithmic electron transmission still holds valid for
      effective specimen thicknesses up to 5 microm under 2 MV accelerating voltages.
      Electron tomography of a micron-order thick integrated circuit specimen including
      the Cu/via interconnect was then tried with 3 MeV electrons in the ultra-HVEM.
      Serial projection images of the specimen tilted at different angles over the
      range of +/-90 degrees were acquired, and 3D reconstruction was performed with
      the images by means of the IMOD software package. Consequently, the 3D structures
      of the Cu lines, via and void, were revealed by cross sections and surface
      rendering.

PMID- 17503923
TI  - Feedforward control of a closed-loop piezoelectric translation stage for atomic
      force microscope.
AB  - Simple feedforward ideas are shown to lead to a nearly tenfold increase in the
      effective bandwidth of a closed-loop piezoelectric positioning stage used in
      scanning probe microscopy. If the desired control signal is known in advance, the
      feedforward filter can be acausal: the information about the future can be used
      to make the output of the stage have almost no phase lag with respect to the
      input. This keeps in register the images assembled from right and left scans. We
      discuss the design constraints imposed by the need for the feedforward filter to
      work robustly under a variety of circumstances. Because the feedforward needs
      only to modify the input signal, it can be added to any piezoelectric stage,
      whether closed or open loop.

PMID- 17503924
TI  - High-yield synthesis of conductive carbon nanotube tips for multiprobe scanning
      tunneling microscope.
AB  - We have established a fabrication process for conductive carbon nanotube (CNT)
      tips for multiprobe scanning tunneling microscope (STM) with high yield. This was
      achieved, first, by attaching a CNT at the apex of a supporting W tip by a
      dielectrophoresis method, second, by reinforcing the adhesion between the CNT and
      the W tip by electron beam deposition of hydrocarbon and subsequent heating, and
      finally by wholly coating it with a thin metal layer by pulsed laser deposition.
      More than 90% of the CNT tips survived after long-distance transportation in air,
      indicating the practical durability of the CNT tips. The shape of the CNT tip did
      not change even after making contact with another metal tip more than 100 times
      repeatedly, which evidenced its mechanical robustness. We exploited the CNT tips
      for the electronic transport measurement by a four-terminal method in a
      multiprobe STM, in which the PtIr-coated CNT portion of the tip exhibited
      diffusive transport with a low resistivity of 1.8 kOmega/microm. The contact
      resistance at the junction between the CNT and the supporting W tip was estimated
      to be less than 0.7 kOmega. We confirmed that the PtIr thin layer remained at the
      CNT-W junction portion after excess current passed through, although the PtIr
      layer was peeled off on the CNT to aggregate into particles, which was likely due
      to electromigration or a thermally activated diffusion process. These results
      indicate that the CNT tips fabricated by our recipe possess high reliability and
      reproducibility sufficient for multiprobe STM measurements.

PMID- 17503925
TI  - Construction of a dilution refrigerator cooled scanning force microscope.
AB  - We present a scanning force microscope that operates in a dilution refrigerator
      at temperatures of about 100 mK. We use tuning fork sensors for scanning gate
      experiments on mesoscopic semiconductor nanostructures. Slip-stick motors allow
      sample coarse-positioning at base temperature. The construction, thermal
      anchoring, and a procedure to optimize the settings of the phase-locked loop that
      we use for sensor control are discussed in detail. We present low-temperature
      topographic and scanning gate images as examples of successful operation.

PMID- 17503926
TI  - WSXM: a software for scanning probe microscopy and a tool for nanotechnology.
AB  - In this work we briefly describe the most relevant features of WSXM, a freeware
      scanning probe microscopy software based on MS-Windows. The article is structured
      in three different sections: The introduction is a perspective on the importance
      of software on scanning probe microscopy. The second section is devoted to
      describe the general structure of the application; in this section the
      capabilities of WSXM to read third party files are stressed. Finally, a detailed
      discussion of some relevant procedures of the software is carried out.

PMID- 17503927
TI  - Novel nanobubble inflation method for determining the viscoelastic properties of
      ultrathin polymer films.
AB  - We describe a novel experimental technique for measuring the viscoelastic
      properties of ultrathin polymer films. The method is based on the classic bubble
      inflation technique for measuring the biaxial creep compliance of films, reduced
      in size to measure films with thicknesses down to at least 13 nm. The method uses
      the imaging capabilities of the atomic force microscope to determine the time
      evolution of the geometry of nanobubbles. Using these data, along with the
      applied pressure, the absolute creep compliance of the films can be determined.

PMID- 17503928
TI  - Oscillation-induced static deflection in scanning force microscopy.
AB  - Employing an atomic force microscope (AFM) in conjunction with a quartz crystal
      microbalance, we have investigated how a high-frequency lateral oscillation of
      the substrate influences the imaging process of the AFM. It was found that the
      time-averaged deflection of the cantilever (both vertical and lateral) changed
      when the oscillation of the quartz resonator was turned on. The vertical-tip
      substrate distance increased, while the lateral force of sliding decreased at the
      same time. A mode of imaging based on this effect was demonstrated. The
      oscillation was periodically interrupted at a rate of 73 Hz and the corresponding
      periodic modulation of the deflection was filtered and amplified using lock-in
      amplifiers. Slowly scanning the sample and displaying the outputs of the lock-in
      amplifiers versus x and y produced an image of the oscillation-induced static
      (OIS) deflection. Various mechanisms by which a lateral oscillation can generate
      a time-averaged vertical force are discussed. The fact that the vertical OIS
      deflection scaled linearly with amplitude and, also, that the OIS deflection was
      stronger on the sloped portions of the sample than on the flat regions, suggests
      a geometric interpretation. We term the phenomenon "cobble stone effect."
      Experiments in liquids showed that the generation of an OIS deflection required
      immediate contact between the sample and the tip: a search for an OIS deflection
      in the presence of a liquid-filled gap between the sample and the tip yielded a
      negative result. Hydrodynamic forces are thereby ruled out as dominating factors.

PMID- 17503929
TI  - Novel sensor design for torque magnetometry.
AB  - Torque magnetometry is a powerful method to determine a sample's magnetic
      properties. In a torque magnetometer, the sample under interest is mounted on a
      suitable sensor, the core part of the instrument. Piezoresistive atomic force
      microscope tips are proven to be very useful torque sensors and have already been
      optimized for the specific needs of torque magnetometry. However, this type of
      sensor did not offer the possibility of measuring torque along two perpendicular
      directions simultaneously without sacrificing sensitivity. In this article we
      demonstrate a fundamentally new sensor design based on the piezoresistive readout
      technique, which offers a large variability of measurement modes. With a
      symmetric arrangement of the sensor legs, concurrent two-axis measurements are
      easily possible with two separate readout circuits. Furthermore, the variability
      can be exploited by fabricating a thermometer on the sample platform to directly
      measure the sample temperature. Test measurements are in good agreement with
      elasticity calculations.

PMID- 17503930
TI  - High saturation solar light beam induced current scanning of solar cells.
AB  - The response of the electrical parameters of photovoltaic cells under
      concentrated solar irradiance has been the subject of many studies performed in
      recent times. The high saturation conditions typically found in solar cells that
      are subjected to highly concentrated solar radiation may cause electrically
      active cell features to behave differently than under monochromatic laser
      illumination, normally used in light beam induced current (LBIC) investigations.
      A high concentration solar LBIC (S-LBIC) measurement system has been developed to
      perform localized cell characterization. The responses of silicon solar cells
      that were measured qualitatively include externally biased induced cell current
      at specific cell voltages, I(V), open circuit voltage, V(oc), and the average
      rate of change of the cell bias with the induced current, DeltaV/DeltaI(V), close
      to the zero bias region. These images show the relative scale of the parameters
      of a cell up to the penetration depth of the solar beam and can be obtained with
      relative ease, qualifying important electrical response features of the solar
      cell. The S-LBIC maps were also compared with maps that were similarly obtained
      using a high intensity He-Ne laser beam probe. This article reports on the
      techniques employed and initial results obtained.

PMID- 17503931
TI  - Noncatalytic thermocouple coatings produced with chemical vapor deposition for
      flame temperature measurements.
AB  - Chemical vapor deposition (CVD) and metal-organic chemical vapor deposition
      (MOCVD) have been employed to develop alumina thin films in order to protect
      thermocouples from catalytic overheating in flames and to minimize the intrusion
      presented to the combustion process. Alumina films obtained with a CVD process
      using AlCl(3) as the precursor are dense, not contaminated, and crystallize in
      the corundum structure, while MOCVD using Al(acetyl acetone)(3) allows the growth
      of corundum alumina with improved growth rates. These films, however, present a
      porous columnar structure and show some carbon contamination. Therefore, coated
      thermocouples using AlCl(3)-CVD were judged more suitable for flame temperature
      measurements and were tested in different fuels over a typical range of
      stoichiometries. Coated thermocouples exhibit satisfactory measurement
      reproducibility, no temporal drifts, and do not suffer from catalytic effects.
      Furthermore, their increased radiative heat loss (observed by infrared
      spectroscopy) allows temperature measurements over a wider range when compared to
      uncoated thermocouples. A flame with a well-known temperature profile established
      with laser-based techniques was used to determine the radiative heat loss
      correction to account for the difference between the apparent temperature
      measured by the coated thermocouple and the true flame temperature. The validity
      of the correction term was confirmed with temperature profile measurements for
      several flames previously studied in different laboratories with laser-based
      techniques.

PMID- 17503932
TI  - A pulsed electron gun for ultrafast electron diffraction at surfaces.
AB  - The construction of a pulsed electron gun for ultrafast reflection high-energy
      electron diffraction experiments at surfaces is reported. Special emphasis is
      placed on the characterization of the electron source: a photocathode, consisting
      of a 10 nm thin Au film deposited onto a sapphire substrate. Electron pulses are
      generated by the illumination of the film with ultraviolet laser pulses of
      femtosecond duration. The photoelectrons are emitted homogeneously across the
      photocathode with an energy distribution of 0.1 eV width. After leaving the Au
      film, the electrons are accelerated to kinetic energies of up to 15 keV. Focusing
      is accomplished by an electrostatic lens. The temporal resolution of the
      experiment is determined by the probing time of the electrons traveling across
      the surface which is about 30 ps. However, the duration of the electron pulses
      can be reduced to less than 6 ps.

PMID- 17503933
TI  - Automated sample exchange and tracking system for neutron research at cryogenic
      temperatures.
AB  - An automated system for sample exchange and tracking in a cryogenic environment
      and under remote computer control was developed. Up to 24 sample "cans" per cycle
      can be inserted and retrieved in a programed sequence. A video camera acquires a
      unique identification marked on the sample can to provide a record of the
      sequence. All operations are coordinated via a LABVIEW program that can be
      operated locally or over a network. The samples are contained in vanadium cans of
      6-10 mm in diameter and equipped with a hermetically sealed lid that interfaces
      with the sample handler. The system uses a closed-cycle refrigerator (CCR) for
      cooling. The sample was delivered to a precooling location that was at a
      temperature of approximately 25 K, after several minutes, it was moved onto a
      "landing pad" at approximately 10 K that locates the sample in the probe beam.
      After the sample was released onto the landing pad, the sample handler was
      retracted. Reading the sample identification and the exchange operation takes
      approximately 2 min. The time to cool the sample from ambient temperature to
      approximately 10 K was approximately 7 min including precooling time. The cooling
      time increases to approximately 12 min if precooling is not used. Small
      differences in cooling rate were observed between sample materials and for
      different sample can sizes. Filling the sample well and the sample can with low
      pressure helium is essential to provide heat transfer and to achieve useful
      cooling rates. A resistive heating coil can be used to offset the refrigeration
      so that temperatures up to approximately 350 K can be accessed and controlled
      using a proportional-integral-derivative control loop. The time for the landing
      pad to cool to approximately 10 K after it has been heated to approximately 240 K
      was approximately 20 min.

PMID- 17503934
TI  - Field and laboratory emission cell automation and control system for
      investigating surface chemistry reactions.
AB  - A novel system [field and laboratory emission cell (FLEC) automation and control
      system] has been developed to deliver ozone to a surface utilizing the FLEC to
      simulate indoor surface chemistry. Ozone, humidity, and air flow rate to the
      surface were continuously monitored using an ultraviolet ozone monitor, humidity,
      and flow sensors. Data from these sensors were used as feedback for system
      control to maintain predetermined experimental parameters. The system was used to
      investigate the chemistry of ozone with alpha-terpineol on a vinyl surface over
      72 h. Keeping all other experimental parameters the same, volatile organic
      compound emissions from the vinyl tile with alpha-terpineol were collected from
      both zero and 100 ppb (parts per 10(9)) ozone exposures. System stability
      profiles collected from sensor data indicated experimental parameters were
      maintained to within a few percent of initial settings. Ozone data from eight
      experiments at 100 ppb (over 339 h) provided a pooled standard deviation of 1.65
      ppb and a 95% tolerance of 3.3 ppb. Humidity data from 17 experiments at 50%
      relative humidity (over 664 h) provided a pooled standard deviation of 1.38% and
      a 95% tolerance of 2.77%. Data of the flow rate of air flowing through the FLEC
      from 14 experiments at 300 ml/min (over 548 h) provided a pooled standard
      deviation of 3.02 ml/min and a 95% tolerance range of 6.03 ml/min. Initial
      experimental results yielded long term emissions of ozone/alpha-terpineol
      reaction products, suggesting that surface chemistry could play an important role
      in indoor environments.

PMID- 17503935
TI  - Large area mass analyzer instrument for the chemical analysis of interstellar
      dust particles.
AB  - A new instrument to analyze the chemical composition of dust particles in situ in
      space has been developed. The large target area ( approximately 0.2 m(2)) makes
      this instrument well suited for detecting a statistically significant number of
      interstellar dust grains or other dust particles with a low flux. The device is a
      reflectron-type time-of-flight mass spectrometer that uses only flat electrodes
      for the generation of the parabolic potential. The instrument analyzes the ions
      from the impact generated plasma due to hypervelocity dust impacts onto a solid
      target surface. The SIMION ion optics software package is used to investigate
      different potential field configurations and optimize the mass resolution and
      focusing of the ions. The cylindrically symmetric instrument operates with six
      ring electrodes and six annular electrodes biased to different potentials to
      create the potential distribution of the reflectron. The laboratory model of the
      instrument has been fabricated and tested. Hypervelocity dust impacts are
      simulated by laser ablation using a frequency doubled Nd:YAG laser with
      approximately 8 ns pulse length. The experimental data show typical mass
      resolution m/Deltam approximately 200.

PMID- 17503936
TI  - Lock-in amplifier error prediction and correction in frequency sweep
      measurements.
AB  - This article proposes an analytical algorithm for predicting errors in lock-in
      amplifiers (LIAs) working with time-varying reference frequency. Furthermore, a
      simple method for correcting such errors is presented. The reference frequency
      can be swept in order to measure the frequency response of a system within a
      given spectrum. The continuous variation of the reference frequency produces a
      measurement error that depends on three factors: the sweep speed, the LIA low
      pass filters, and the frequency response of the measured system. The proposed
      error prediction algorithm is based on the final value theorem of the Laplace
      transform. The correction method uses a double-sweep measurement. A mathematical
      analysis is presented and validated with computational simulations and
      experimental measurements.

PMID- 17503937
TI  - Software defined photon counting system for time resolved x-ray experiments.
AB  - The time structure of synchrotron radiation allows time resolved experiments with
      sub-100 ps temporal resolution using a pump-probe approach. However, the
      relaxation time of the samples may require a lower repetition rate of the pump
      pulse compared to the full repetition rate of the x-ray pulses from the
      synchrotron. The use of only the x-ray pulse immediately following the pump pulse
      is not efficient and often requires special operation modes where only a few
      buckets of the storage ring are filled. We designed a novel software defined
      photon counting system that allows to implement a variety of pump-probe schemes
      at the full repetition rate. The high number of photon counters allows to detect
      the response of the sample at multiple time delays simultaneously, thus improving
      the efficiency of the experiment. The system has been successfully applied to
      time resolved scanning transmission x-ray microscopy. However, this technique is
      applicable more generally.

PMID- 17503938
TI  - Practical and simple circuitry for the measurement of small capacitance.
AB  - Practical and cost-effective circuitry with high sensitivity has been developed
      to measure a small capacitance using current compensation method. The circuitry
      uses an electronic switch to periodically connect or separate the capacitor under
      test (C(x)) from a reference capacitor (C(r)). When C(x) is connected in parallel
      with C(r) the total capacitance becomes C(x)+C(r). On the other hand, as C(x) is
      separated from C(r), the total capacitance is only C(r). This periodic change of
      the capacitance generates a periodic square-wave output with an amplitude in
      proportion to the capacitance of C(x). A high sensitivity of DeltaV/DeltaC=202.2
      mV/pF has been achieved, making the circuitry a powerful tool in measuring small
      capacitances. Three applications have been performed to present its capability:
      (a) displacement, (b) height of liquid, and (c) angle of tilt. The experimental
      results demonstrate the performance of the circuitry.

PMID- 17503939
TI  - Three-axis acoustic device for levitation of droplets in an open gas stream and
      its application to examine sulfur dioxide absorption by water droplets.
AB  - Two acoustic devices to stabilize a droplet in an open gas stream (single-axis
      and three-axis levitators) have been designed and tested. The gas stream was
      provided by a jet apparatus with a 64 mm exit diameter and a uniform velocity
      profile. The acoustic source used was a Langevin vibrator with a concave
      reflector. The single-axis levitator relied primarily on the radial force from
      the acoustic field and was shown to be limited because of significant droplet
      wandering. The three-axis levitator relied on a combination of the axial and
      radial forces. The three-axis levitator was applied to examine droplet
      deformation and circulation and to investigate the uptake of SO(2) from the gas
      stream to the droplet. Droplets ranging in diameters from 2 to 5 mm were
      levitated in gas streams with velocities up to 9 ms. Droplet wandering was on the
      order of a half droplet diameter for a 3 mm diameter droplet. Droplet circulation
      ranged from the predicted Hadamard-Rybczynski pattern to a rotating droplet
      pattern. Droplet pH over a central volume of the droplet was measured by planar
      laser induced fluorescence. The results for the decay of droplet pH versus time
      are in general agreement with published theory and experiments.

PMID- 17503940
TI  - Force detected electron spin resonance at 94 GHz.
AB  - Force detected electron spin resonance (FDESR) detects the presence of unpaired
      electrons in a sample by measuring the change in force on a mechanical resonator
      as the magnetization of the sample is modulated under magnetic resonance
      conditions. The magnetization is coupled to the resonator via a magnetic field
      gradient. It has been used to both detect and image distributions of electron
      spins, and it offers both extremely high absolute sensitivity and high spatial
      imaging resolution. However, compared to conventional induction mode ESR the
      technique also has a comparatively poor concentration sensitivity and it
      introduces complications in interpreting and combining both spectroscopy and
      imaging. One method to improve both sensitivity and spectral resolution is to
      operate in high magnetic fields in order to increase the sample magnetization and
      g-factor resolution. In this article we present FDESR measurements on the organic
      conductor (fluoranthene)(2)PF(6) at 3.2 T, with a corresponding millimeter-wave
      frequency of 93.5 GHz, which we believe are the highest field results for FDESR
      reported in the literature to date. A magnet-on-cantilever approach was used,
      with a high-anisotropy microwave ferrite as the gradient source and employing
      cyclic saturation to modulate the magnetization at the cantilever fundamental
      frequency.

PMID- 17503941
TI  - Four-channel magnetic resonance imaging receiver using frequency domain
      multiplexing.
AB  - An alternative technique that uses frequency domain multiplexing to acquire
      phased array magnetic resonance images is discussed in detail. The proposed
      method has advantages over traditional independent receiver chains in that it
      utilizes an analog-to-digital converter and a single-chip multicarrier receiver
      with high performance to reduce the size and cost of the phased array receiver
      system. A practical four-channel digital receiver using frequency domain
      multiplexing was implemented and verified on a home-built 0.3 T magnetic
      resonance imaging system. The experimental results confirmed that the cross talk
      between each channel was below -60 dB, the phase fluctuations were about 1
      degrees , and there was no obvious signal-to-noise ratio degradation. It is
      demonstrated that the frequency domain multiplexing is a valuable and economical
      technique, particularly for array coil systems where the multichannel receiver is
      indispensable and dynamic range is not a critical problem.

PMID- 17503942
TI  - Acousto-optic modulator system for femtosecond laser pulses.
AB  - Femtosecond laser pulses have made a revolution in multiphoton excitation
      microscopy, micromachining, and optical storage for their unprecedented high peak
      power. However, modulation of their intensity with acousto-optic modulator (AOM)
      is frustrated by dispersion which results in a significant stretch in pulse
      width. Here we report a scheme composed of two acousto-optic deflectors (AODs) to
      modulate the intensity of the femtosecond laser pulses with simultaneous
      compensation for the temporal dispersion. With commercial AODs, we demonstrated
      such an AOM system for the femtosecond laser pulses with overall transmission
      efficiency of around 80%. The pulse width of the exit beam is 115-177 fs for an
      input pulse of 110 fs, across the wavelength range of 720-920 nm when the
      temporal dispersion compensation is optimally tuned at 800 nm. The fluorescence
      intensity in a two-photon microscopy experiment performed using this system
      increased 5.5-fold over that of the uncompensated AOM.

PMID- 17503943
TI  - Cold plasma brush generated at atmospheric pressure.
AB  - A cold plasma brush is generated at atmospheric pressure with low power
      consumption in the level of several watts (as low as 4 W) up to tens of watts (up
      to 45 W). The plasma can be ignited and sustained in both continuous and pulsed
      modes with different plasma gases such as argon or helium, but argon was selected
      as a primary gas for use in this work. The brush-shaped plasma is formed and
      extended outside of the discharge chamber with typical dimension of 10-15 mm in
      width and less than 1.0 mm in thickness, which are adjustable by changing the
      discharge chamber design and operating conditions. The brush-shaped plasma
      provides some unique features and distinct nonequilibrium plasma characteristics.
      Temperature measurements using a thermocouple thermometer showed that the gas
      phase temperatures of the plasma brush are close to room temperature (as low as
      42 degrees C) when running with a relatively high gas flow rate of about 3500
      ml/min. For an argon plasma brush, the operating voltage from less than 500 V to
      about 2500 V was tested, with an argon gas flow rate varied from less than 1000
      to 3500 ml/min. The cold plasma brush can most efficiently use the discharge
      power as well as the plasma gas for material and surface treatment. The very low
      power consumption of such an atmospheric argon plasma brush provides many unique
      advantages in practical applications including battery-powered operation and use
      in large-scale applications. Several polymer film samples were tested for surface
      treatment with the newly developed device, and successful changes of the
      wettability property from hydrophobic to hydrophilic were achieved within a few
      seconds.

PMID- 17503944
TI  - Novel apparatus for joining of carbon-carbon composites.
AB  - A novel apparatus for joining carbon-carbon (C-C) composites is presented. This
      device was designed and built based on the concept of self-sustained oxygen-free
      high-temperature reactions. A layer of reactive mixture is contained between two
      disks of C-C composite that are to be joined. The stack is held in place between
      two electrodes, which are connected to a dc power supply. dc current is used to
      uniformly initiate the reaction in the reactive layer. The electrodes are also
      part of the pneumatic system, which applies a load to the stack. The designed
      hydraulic system is effective, lending to low cost and simplified, rapid,
      accurate operation. It provides a very short response time ( approximately 10
      ms), which is important for the considered applications. All operational
      parameters such as initial and final loads, applied current, delay time between
      ignition and final load application, duration of Joule heating, and safety
      interlocks are controlled by a programable logic controller system. These
      features make it an efficient, user-friendly and safe machine to join refractory
      materials. The entire joining process takes place on the order of seconds, rather
      than hours as required for solid-state joining methods. The mechanical properties
      of the obtained joints are higher than those for the C-C composites.

PMID- 17503945
TI  - Manometer extension for high pressure measurement: nuclear quadrupole resonance
      study of Cu2O with a modified Bridgman anvil cell up to 10 GPa.
AB  - We report (63)Cu nuclear quadrupole resonance (NQR) measurement of Cu(2)O under
      pressure up to about 10 GPa at low temperatures. Because the lattice parameter of
      Cu(2)O changes with increasing pressure, the electric field gradient at the Cu
      site also changes correspondingly with pressure. This enables us to use the
      Cu(2)O as an in situ manometer for high pressure nuclear magnetic resonance/NQR
      up to about 9 GPa.

PMID- 17503946
TI  - Design, microfabrication, and analysis of micrometer-sized cylindrical ion trap
      arrays.
AB  - A description of the design and microfabrication of arrays of micrometer-scale
      cylindrical ion traps is offered. Electrical characterization and initial ion
      trapping experiments with a massively parallel array of 5 microm internal radius
      (r(0)) sized cylindrical ion traps (CITs) are also described. The ion trap,
      materials, and design are presented and shown to be critical in achieving minimal
      trapping potential while maintaining minimal power consumption. The ion traps,
      fabricated with metal electrodes, have inner radii of 1, 2, 5, and 10 microm and
      range from 5 to 24 microm in height. The electrical characteristics of packaged
      ion trap arrays were measured with a vector network analyzer. The testing focused
      on trapping toluene (C(7)H(8)), mass 91, 92, or 93 amu, in the 5 microm sized
      CITs. Ions were formed via electron impact ionization and were ejected by turning
      off the rf voltage applied to the ring electrode; a current signal was collected
      at this time. Optimum ionization and trapping conditions, such as a sufficient
      pseudopotential well and high ionization to ion loss rate ratio (as determined by
      simulation), proved to be difficult to establish due to the high device
      capacitance and the presence of exposed dielectric material in the trapping
      region. However, evidence was obtained suggesting the trapping of ions in 1%-15%
      of the traps in the array. These first tests on micrometer-scale CITs indicated
      the necessary materials and device design modifications for realizing ultrasmall
      and low power ion traps.

PMID- 17503947
TI  - Novel liquid flow sensor based on differential pressure method.
AB  - In this article, a novel liquid flow sensor which is composed of a special
      structure conduit main body and a differential pressure sensor was designed,
      fabricated, and calibrated. The conduit main body includes an inlet channel
      section with a branch conduit connecting one end of the pressure sensor, a throat
      channel section, and an outlet channel section with a branch conduit connecting
      another end of the pressure sensor. The basic principle is to employ a
      differential pressure sensor to measure the pressure difference between the inlet
      channel and outlet channel of the conduit main body when fluid passes through it.
      The pressure difference between the two ends of the differential pressure sensor
      (i.e., the two branch conduits located in the inlet and outlet channel sections)
      is of either forward or backward flow and directly interrelates with the volume
      flow rate (mass flow rate or flow velocity) via the conduit main body, so the
      volume flow rate or mass flow rate or flow velocity can be calculated and the
      flow direction can be determined from the detected pressure difference. This
      liquid flow sensor is characterized by using only one differential pressure
      sensor of a simple structure, the error of which is less than 1%.

PMID- 17503948
TI  - A rheo-optical apparatus for real time kinetic studies on shear-induced alignment
      of self-assembled soft matter with small sample volumes.
AB  - In soft materials, self-assembled nanoscale structures can allow new
      functionalities but a general problem is to align such local structures aiming at
      monodomain overall order. In order to achieve shear alignment in a controlled
      manner, a novel type of rheo-optical apparatus has here been developed that
      allows small sample volumes and in situ monitoring of the alignment process
      during the shear. Both the amplitude and orientation angles of low level linear
      birefringence and dichroism are measured while the sample is subjected to large
      amplitude oscillatory shear flow. The apparatus is based on a commercial
      rheometer where we have constructed a flow cell that consists of two quartz
      teeth. The lower tooth can be set in oscillatory motion whereas the upper one is
      connected to the force transducers of the rheometer. A custom made cylindrical
      oven allows the operation of the flow cell at elevated temperatures up to 200
      degrees C. Only a small sample volume is needed (from 9 to 25 mm(3)), which makes
      the apparatus suitable especially for studying new materials which are usually
      obtainable only in small quantities. Using this apparatus the flow alignment
      kinetics of a lamellar polystyrene-b-polyisoprene diblock copolymer is studied
      during shear under two different conditions which lead to parallel and
      perpendicular alignment of the lamellae. The open device geometry allows even
      combined optical/x-ray in situ characterization of the alignment process by
      combining small-angle x-ray scattering using concepts shown by Polushkin et al.
      [Macromolecules 36, 1421 (2003)].

PMID- 17503949
TI  - Ultrasonic torsional guided wave sensor for flow front monitoring inside molds.
AB  - Measuring the extent of flow of viscous fluids inside opaque molds has been a
      very important parameter in determining the quality of products in the
      manufacturing process such as injection molding and resin transfer molding.
      Hence, in this article, an ultrasonic torsional guided wave sensor has been
      discussed for monitoring the movement of flow front during filling of resins in
      opaque molds. A pair of piezoelectric normal shear transducers were used for
      generating and receiving the fundamental ultrasonic torsional guided wave mode in
      thin copper wires. The torsional mode was excited at one end of the wire, while
      the flowing viscous fluid progressively wet the other free end of the wire. The
      time of flight of the transient reflections of this fundamental mode from the air
      fluid interface, where the wire enters the resin, was used to measure the
      position of the fluid flow front. Experiments were conducted on four fluids with
      different viscosity values. Two postprocessing algorithms were developed for
      enhancing the transient reflected signal and for suppressing the unwanted
      stationary signals. The algorithms were tested for cases where the reflected
      signals showed a poor signal to noise ratio.

PMID- 17503950
TI  - Cross-talk correction in atomic force microscopy.
AB  - Commercial atomic force microscopes usually use a position-sensitive photodiode
      to detect the motion of the cantilever via laser beam deflection. This readout
      technique makes it possible to measure bending and torsion of the cantilever
      separately. A slight angle between the orientation of the photodiode and the
      plane of the readout laser beam, however, causes false signals in both readout
      channels. This cross-talk may lead to misinterpretation of the acquired data. We
      demonstrate this fault with images recorded in contact mode on periodically poled
      ferroelectric crystals and present a simple electronic circuit to compensate for
      it. This circuit can correct for cross-talk with a bandwidth of approximately 1
      MHz suppressing the the false signal to <<1%.

PMID- 17503951
TI  - Electrical characterization of a capacitive rf plasma sheath.
AB  - The authors report on an experimental system designed to investigate and
      characterize capacitive radio frequency (rf) sheaths. An electrode mounted in an
      inductive plasma reactor and driven with separate rf and direct current (dc)
      power sources is used. The advantage of this design is that the electrode sheath
      is decoupled from the plasma parameters. This allows detailed investigation of
      the sheath with different bias conditions without perturbing the bulk plasma
      parameters. Power coupled to ions and electrons through the sheath, at low
      pressure, is investigated and a method to determine the electron conduction
      current to the electrode, using the external dc bias, is presented.

PMID- 17503952
TI  - Tunable eletro-optical modulators based on a split-ring resonator.
AB  - We present a novel design of an electro-optical modulator setup, consisting of a
      mechanically tunable cavity which allows the modulation frequency to be varied
      over a broad range. The design is based on the frequently used geometry of a
      split-ring resonator which allows for high-efficiency sideband generation.
      Normally such a configuration has the limitation of a narrow excitation band
      width ( approximately 20 MHz). Our adjustable setup offers broad-range tunability
      over several hundred megahertz while still keeping the modulation efficiency.
      Such a widely tunable modulator may find applications in a variety of experiments
      in atomic physics.

PMID- 17503953
TI  - Investigation of water and ice by ac impedance using electrochemical properties
      cup.
AB  - Water and ice were investigated by ac impedance with the electrochemical
      properties cup in an effort to develop an in situ instrument for water
      characterization. In liquid water, the impedance modulus decreased with the
      increase in charge carriers. In the ice, the impedance measurements were
      characterized by the dielectric relaxation and its corresponding activation
      energy. The activation energy of 0.400 eV was determined for pure ice. With ice
      containing Cl(-) anions, the activation energy was 0.24 eV. H(+) and OH(-) doped
      ice has the lowest activation energy for dielectric relaxation. Results from
      previous works are similar to the results reported in this study.

PMID- 17503954
TI  - Lead-free multilayer piezoelectric transformer.
AB  - In this article, a multilayer piezoelectric transformer based on lead-free Mn
      doped 0.94(Bi(12)Na(12))TiO(3)-0.06BaTiO(3) ceramics is presented. This
      piezoelectric transformer, with a multilayered construction in the thickness
      direction, is 8.3 mm long, 8.3 mm wide, and 2.3 mm thick. It operates in the
      second thickness extensional vibration mode. For a temperature rise of 20 degrees
      C, the transformer has an output power of >0.3 W. With a matching load resistance
      of 10 Omega, its maximum efficiency approaches 81.5%, and the maximum voltage
      gain is 0.14. It has potential to be used in low voltage power supply units such
      as low power adapter and other electronic circuits.

PMID- 17503955
TI  - On the development of a confocal Rayleigh-Brillouin microscope.
AB  - This Note illustrates how a confocal microscope may be modified to conduct
      Rayleigh-Brillouin mapping experiments that yield very useful information on the
      mechanical properties of interfacial materials in small volume elements. While
      the modifications to the microscope are quite straightforward, they do entail
      significant changes in the optical design. The instrument described herein
      consists of an argon ion laser equipped with an actively stabilized intercavity
      etalon that serves as the excitation source for a modified Zeiss LSM 310 confocal
      laser scan microscope. The optics of the microscope were reconfigured to enable
      interfacing of the microscope with a tandem triple-pass Fabry-Perot
      interferometer. This instrument enables three-dimensional Rayleigh-Brillouin
      spectral mapping of samples at micron spatial resolution. The performance of the
      instrument and its ability to perform both lateral and depth scans of the
      acoustic phonon velocity and, hence, the longitudinal modulus across bonded
      polymer/polymer and polymer/ceramic interfaces are illustrated and discussed.

PMID- 17503959
TI  - Chronic obstructive pulmonary disease: a growing but neglected global epidemic.

PMID- 17503960
TI  - Childhood conditions influence adult progesterone levels.
AB  - BACKGROUND: Average profiles of salivary progesterone in women vary significantly
      at the inter- and intrapopulation level as a function of age and acute energetic
      conditions related to energy intake, energy expenditure, or a combination of
      both. In addition to acute stressors, baseline progesterone levels differ among
      populations. The causes of such chronic differences are not well understood, but
      it has been hypothesised that they may result from varying tempos of growth and
      maturation and, by implication, from diverse environmental conditions encountered
      during childhood and adolescence. METHODS AND FINDINGS: To test this hypothesis,
      we conducted a migrant study among first- and second-generation Bangladeshi women
      aged 19-39 who migrated to London, UK at different points in the life-course,
      women still resident in Bangladesh, and women of European descent living in
      neighbourhoods similar to those of the migrants in London (total n = 227). Data
      collected included saliva samples for radioimmunoassay of progesterone,
      anthropometrics, and information from questionnaires on diet, lifestyle, and
      health. Results from multiple linear regression, controlled for anthropometric
      and reproductive variables, show that women who spend their childhood in
      conditions of low energy expenditure, stable energy intake, good sanitation, low
      immune challenges, and good health care in the UK have up to 103% higher levels
      of salivary progesterone and an earlier maturation than women who develop in less
      optimal conditions in Sylhet, Bangladesh (F9,178 = 5.05, p < 0.001, standard
      error of the mean = 0.32; adjusted R(2) = 0.16). Our results point to the period
      prior to puberty as a sensitive phase when changes in environmental conditions
      positively impact developmental tempos such as menarcheal age (F2,81 = 3.21, p =
      0.03) and patterns of ovarian function as measured using salivary progesterone
      (F2,81 = 3.14, p = 0.04). CONCLUSIONS: This research demonstrates that human
      females use an extended period of the life cycle prior to reproductive maturation
      to monitor their environment and to modulate reproductive steroid levels in
      accordance with projected conditions they might encounter as adults. Given the
      prolonged investment of human pregnancy and lactation, such plasticity (extending
      beyond any intrauterine programming) enables a more flexible and finely tuned
      adjustment to the potential constraints or opportunities of the later adult
      environment. This research is the first, to our knowledge, to demonstrate a
      postuterine developmental component to variation in reproductive steroid levels
      in women.

PMID- 17503961
TI  - Isoform-specific potentiation of stem and progenitor cell engraftment by
      AML1/RUNX1.
AB  - BACKGROUND: AML1/RUNX1 is the most frequently mutated gene in leukaemia and is
      central to the normal biology of hematopoietic stem and progenitor cells.
      However, the role of different AML1 isoforms within these primitive compartments
      is unclear. Here we investigate whether altering relative expression of AML1
      isoforms impacts the balance between cell self-renewal and differentiation in
      vitro and in vivo. METHODS AND FINDINGS: The human AML1a isoform encodes a
      truncated molecule with DNA-binding but no transactivation capacity. We used a
      retrovirus-based approach to transduce AML1a into primitive haematopoietic cells
      isolated from the mouse. We observed that enforced AML1a expression increased the
      competitive engraftment potential of murine long-term reconstituting stem cells
      with the proportion of AML1a-expressing cells increasing over time in both
      primary and secondary recipients. Furthermore, AML1a expression dramatically
      increased primitive and committed progenitor activity in engrafted animals as
      assessed by long-term culture, cobblestone formation, and colony assays. In
      contrast, expression of the full-length isoform AML1b abrogated engraftment
      potential. In vitro, AML1b promoted differentiation while AML1a promoted
      proliferation of progenitors capable of short-term lymphomyeloid engraftment.
      Consistent with these findings, the relative abundance of AML1a was highest in
      the primitive stem/progenitor compartment of human cord blood, and forced
      expression of AML1a in these cells enhanced maintenance of primitive potential
      both in vitro and in vivo. CONCLUSIONS: These data demonstrate that the "a"
      isoform of AML1 has the capacity to potentiate stem and progenitor cell
      engraftment, both of which are required for successful clinical transplantation.
      This activity is consistent with its expression pattern in both normal and
      leukaemic cells. Manipulating the balance of AML1 isoform expression may offer
      novel therapeutic strategies, exploitable in the contexts of leukaemia and also
      in cord blood transplantation in adults, in whom stem and progenitor cell numbers
      are often limiting.

PMID- 17503962
TI  - Migrating ovaries: early life influences on later gonadal function.

PMID- 17503963
TI  - Evidence of a large-scale functional organization of Mammalian chromosomes.

PMID- 17503965
TI  - Cetaceans have complex brains for complex cognition.

PMID- 17503966
TI  - The undergraduate genomics research initiative.

PMID- 17503967
TI  - Survival of the likeliest?

PMID- 17503970
TI  - Series introduction and cardiovascular disease in patients with schizophrenia.

PMID- 17503968
TI  - A K ATP channel-dependent pathway within alpha cells regulates glucagon release
      from both rodent and human islets of Langerhans.
AB  - Glucagon, secreted from pancreatic islet alpha cells, stimulates gluconeogenesis
      and liver glycogen breakdown. The mechanism regulating glucagon release is
      debated, and variously attributed to neuronal control, paracrine control by
      neighbouring beta cells, or to an intrinsic glucose sensing by the alpha cells
      themselves. We examined hormone secretion and Ca(2+) responses of alpha and beta
      cells within intact rodent and human islets. Glucose-dependent suppression of
      glucagon release persisted when paracrine GABA or Zn(2+) signalling was blocked,
      but was reversed by low concentrations (1-20 muM) of the ATP-sensitive K(+)
      (KATP) channel opener diazoxide, which had no effect on insulin release or beta
      cell responses. This effect was prevented by the KATP channel blocker tolbutamide
      (100 muM). Higher diazoxide concentrations (>/=30 muM) decreased glucagon and
      insulin secretion, and alpha- and beta-cell Ca(2+) responses, in parallel. In the
      absence of glucose, tolbutamide at low concentrations (<1 muM) stimulated
      glucagon secretion, whereas high concentrations (>10 muM) were inhibitory. In the
      presence of a maximally inhibitory concentration of tolbutamide (0.5 mM), glucose
      had no additional suppressive effect. Downstream of the KATP channel, inhibition
      of voltage-gated Na(+) (TTX) and N-type Ca(2+) channels (omega-conotoxin), but
      not L-type Ca(2+) channels (nifedipine), prevented glucagon secretion. Both the N
      type Ca(2+) channels and alpha-cell exocytosis were inactivated at depolarised
      membrane potentials. Rodent and human glucagon secretion is regulated by an alpha
      cell KATP channel-dependent mechanism. We propose that elevated glucose reduces
      electrical activity and exocytosis via depolarisation-induced inactivation of ion
      channels involved in action potential firing and secretion.

PMID- 17503969
TI  - Drosophila brakeless interacts with atrophin and is required for tailless
      mediated transcriptional repression in early embryos.
AB  - Complex gene expression patterns in animal development are generated by the
      interplay of transcriptional activators and repressors at cis-regulatory DNA
      modules (CRMs). How repressors work is not well understood, but often involves
      interactions with co-repressors. We isolated mutations in the brakeless gene in a
      screen for maternal factors affecting segmentation of the Drosophila embryo.
      Brakeless, also known as Scribbler, or Master of thickveins, is a nuclear protein
      of unknown function. In brakeless embryos, we noted an expanded expression
      pattern of the Kruppel (Kr) and knirps (kni) genes. We found that Tailless
      mediated repression of kni expression is impaired in brakeless mutants. Tailless
      and Brakeless bind each other in vitro and interact genetically. Brakeless is
      recruited to the Kr and kni CRMs, and represses transcription when tethered to
      DNA. This suggests that Brakeless is a novel co-repressor. Orphan nuclear
      receptors of the Tailless type also interact with Atrophin co-repressors. We show
      that both Drosophila and human Brakeless and Atrophin interact in vitro, and
      propose that they act together as a co-repressor complex in many developmental
      contexts. We discuss the possibility that human Brakeless homologs may influence
      the toxicity of polyglutamine-expanded Atrophin-1, which causes the human
      neurodegenerative disease dentatorubral-pallidoluysian atrophy (DRPLA).

PMID- 17503971
TI  - Evidence of switching antipsychotic therapy to improve metabolic disturbances.

PMID- 17503973
TI  - Guided discontinuation versus maintenance treatment in remitted first-episode
      psychosis: relapse rates and functional outcome.
AB  - OBJECTIVE: To compare the consequences of a guided discontinuation strategy and
      maintenance treatment in remitted first-episode psychosis in terms of relapse
      rates and functional outcome. METHOD: The study was conducted in 7 mental health
      care organizations and the Department of Psychiatry of the University Medical
      Center Groningen in The Netherlands, covering a catchment area of 3.1 million
      inhabitants. A sample of 131 remitted first-episode patients, aged 18 to 45
      years, with a DSM-IV diagnosis of schizophrenia or related psychotic disorder was
      included (i.e., all patients with a first psychotic episode from October 2001
      through December 2002 who were willing to participate). After 6 months of
      positive symptom remission, they were randomly and openly assigned to the
      discontinuation strategy or maintenance treatment. Maintenance treatment was
      carried out according to American Psychiatric Association guidelines, preferably
      using low-dose atypical antipsychotics. The discontinuation strategy was carried
      out by gradual symptom-guided tapering of dosage and discontinuation if feasible.
      Follow-up was 18 months. Main outcome measures were relapse rates and social and
      vocational functioning. RESULTS: Twice as many relapses occurred with the
      discontinuation strategy (43% vs. 21%, p = .011). Of patients who received the
      strategy, approximately 20% were successfully discontinued. Recurrent symptoms
      caused another approximately 30% to restart antipsychotic treatment, while in the
      remaining patients discontinuation was not feasible at all. There were no
      advantages of the discontinuation strategy regarding functional outcome.
      CONCLUSIONS: Only a limited number of patients can be successfully discontinued.
      High relapse rates do not allow a discontinuation strategy to be universal
      practice. However, if relapse risk can be carefully managed by close monitoring,
      in some remitted first-episode patients a guided discontinuation strategy may
      offer a feasible alternative to maintenance treatment. Further research is needed
      to find predictors of successful discontinuation.

PMID- 17503974
TI  - Aripiprazole effects in patients with acute schizophrenia experiencing higher or
      lower agitation: a post hoc analysis of 4 randomized, placebo-controlled clinical
      trials.
AB  - OBJECTIVE: Patients with acute schizophrenia who are agitated typically manifest
      worse overall symptomatology and are generally more challenging to treat than
      nonagitated patients. In order to determine whether baseline agitation level
      influences treatment response, the effects of oral aripiprazole in acute patients
      with schizophrenia experiencing either higher or lower levels of agitation were
      examined. METHOD: A post hoc analysis of pooled data from the first 4 or 6 weeks
      of 4 randomized, double-blind, placebo-controlled aripiprazole trials was
      conducted. Patients with a DSM-IV diagnosis of acute schizophrenia randomly
      assigned to treatment with either aripiprazole 10, 15, 20, or 30 mg/day (N = 790)
      or placebo (N = 397) were divided into groups experiencing higher or lower
      agitation at baseline. Higher agitation was defined as a baseline Positive and
      Negative Syndrome Scale (PANSS)-Excited Component (PEC) score of > or = 14 and a
      score of > or = 4 on at least 1 PEC item (excitement, hostility, tension,
      uncooperativeness, or poor impulse control). Analysis of covariance was used to
      evaluate PANSS total, Clinical Global Impressions-Improvement scale (CGI-I), and
      PEC scores between aripiprazole and placebo within the higher and lower agitation
      groups. RESULTS: In both the higher and lower agitation groups, aripiprazole
      treatment produced significantly lower PANSS total, CGI-I, and PEC scores at
      weeks 2 to 6, compared with placebo (p < .05 for each measure). Percentage of
      concomitant benzodiazepine use was similar at end point for aripiprazole and
      placebo, and adverse events were generally mild across groups. CONCLUSIONS:
      Aripiprazole significantly improved the core symptoms of acute schizophrenia
      regardless of baseline agitation level. In particular, agitation symptoms were
      significantly decreased in patients with higher baseline agitation. Improvements
      appeared to be independent of benzodiazepine use or excessive sedation effects.
      These results suggest that oral aripiprazole is an effective and safe treatment
      option for patients with acute schizophrenia who manifest agitation symptoms.

PMID- 17503975
TI  - Exercise for mood and anxiety disorders.

PMID- 17503976
TI  - A double-blind, placebo-controlled study of the efficacy and safety of
      desvenlafaxine succinate in the treatment of major depressive disorder.
AB  - OBJECTIVE: This study evaluated the efficacy and safety of desvenlafaxine
      succinate extended-release in major depressive disorder (MDD). METHOD: Adult
      outpatients with DSM-IV-defined MDD were randomly assigned to desvenlafaxine 100
      mg/day (N = 114), 200 mg/day (N = 116), or 400 mg/day (N = 113) or placebo (N =
      118) for 8 weeks. Efficacy variables included change from baseline in the 17-item
      Hamilton Rating Scale for Depression (HAM-D(17), the primary efficacy measure),
      Clinical Global Impressions-Improvement scale (CGI-I), Montgomery-Asberg
      Depression Rating Scale, Clinical Global Impressions-Severity of Illness scale
      (CGI-S), rates of response (> or = 50% decrease from baseline HAM-D(17) score)
      and remission (HAM-D(17) score < or =7), and Visual Analog Scale-Pain Intensity
      overall score. The study was conducted from November 2003 to November 2004.
      RESULTS: At the final on-therapy evaluation, the mean HAM-D(17) scores for
      desvenlafaxine 100 mg/day (12.75) and 400 mg/day (12.50) were significantly lower
      than for placebo (15.31; p = .0038 and p = .0023, respectively); for
      desvenlafaxine 200 mg/day, the mean score was 13.31 (p = .0764). CGI-I and
      Montgomery-Asberg Depression Rating Scale results were significant for all
      groups; CGI-S results were significant with 100 mg/day and 400 mg/day. Response
      rates were significantly greater for desven-lafaxine 100 mg/day (51%) and 400
      mg/day (48%) versus placebo (35%; p = .017 and p = .046, respectively); the
      response rate for desvenlafaxine 200 mg/day was 45% (p = .142). Remission rates
      were significantly greater for desvenlafaxine 400 mg/day (32%) versus placebo
      (19%; p = .035); remission rates were 30% for desvenlafaxine 100 mg/day (p =
      .093) and 28% for desvenlafaxine 200 mg/day (p = .126). Visual Analog Scale-Pain
      Intensity results were significant for desvenlafaxine 100 mg/day versus placebo
      (p = .002), but not for the higher doses. The most commonly reported adverse
      events were nausea, insomnia, somnolence, dry mouth, dizziness, sweating,
      nervousness, anorexia, constipation, asthenia, and abnormal ejaculation/orgasm.
      CONCLUSIONS: Desvenlafaxine is effective and well tolerated in the short-term
      treatment of MDD.

PMID- 17503977
TI  - Decisional capacity to consent to research among patients with bipolar disorder:
      comparison with schizophrenia patients and healthy subjects.
AB  - OBJECTIVE: Although clinical trials are needed to advance treatments for bipolar
      disorder, there has been little empirical research on the capacity of bipolar
      patients to consent to research. The aim of the present study was to evaluate
      levels of decisional capacity of bipolar patients compared with those of
      schizophrenia patients and healthy comparison subjects, as well as to examine
      whether symptom and neurocognitive deficits correlate with patients' decisional
      abilities. METHOD: Participants were 31 outpatients with bipolar disorder, 31
      outpatients with schizophrenia, and 28 healthy comparison subjects; each
      participant's decisional capacity was evaluated with the MacArthur Competence
      Assessment Tool for Clinical Research. Patient participants were also evaluated
      with standardized clinical rating scales and neurocognitive tests. Data were
      collected from April 2002 through November 2005. RESULTS: Bipolar patients had
      worse understanding than healthy comparison subjects, and their level of
      decisional capacity did not differ from that of schizophrenia patients. Within
      the combined patient sample, neurocognitive deficits and negative symptoms were
      significantly correlated (p < .05) with the level of decisional capacity
      (particularly, understanding of disclosed information). Repeating the missed
      information improved the level of understanding in all groups. CONCLUSIONS: The
      presence of bipolar disorder appears to be a risk factor for impaired
      understanding of information disclosed under standard consent procedures but
      should not be equated with a lack of competence to consent. The observed
      improvement in understanding with redisclosure of information suggests that
      enhanced consent procedures may be useful during enrollment of bipolar patients
      in research.

PMID- 17503978
TI  - Impact of CYP1A2 and CYP2D6 polymorphisms on drug metabolism and on insulin and
      lipid elevations and insulin resistance in clozapine-treated patients.
AB  - OBJECTIVE: Adverse metabolic effects of atypical antipsychotics have increasingly
      been recognized. Recently, we found that levels of insulin and triglycerides
      increased by increasing serum clozapine concentration in clozapine-treated
      patients. As these insulin and triglyceride elevations probably are drug
      concentration-dependent, they also would be expected to be drug metabolism
      related. The genetically polymorphic cytochromes P450 CYP1A2 and CYP2D6 catalyze
      the metabolism of clozapine. The aim of this study was to evaluate the impact of
      CYP1A2 and CYP2D6 polymorphisms on serum drug and metabolite levels and on
      insulin and triglyceride elevations and insulin resistance in patients receiving
      clozapine. METHOD: Seventeen clozapine-treated patients were genotyped for CYP1A2
      and CYP2D6 by polymerase chain reaction-based methods. Serum concentrations of
      clozapine and its N-desmethylmetabolite, blood glucose, and serum levels of
      insulin, C-peptide, triglycerides, and cholesterol were analyzed, and homeostasis
      model assessment index for insulin resistance (HOMA-IR) was determined. RESULTS:
      Clozapine and N-desmethylclozapine concentration-to-dose (C/D) ratios were
      significantly higher in patients carrying 2 CYP1A2 single nucleotide
      polymorphisms (SNPs), previously suggested to cause low enzyme activity, compared
      to those with no such SNPs (p < .05). In contrast, clozapine and N
      desmethylclozapine C/D ratios were not related to the CYP2D6 genotype.
      Furthermore, patients with elevated insulin levels more frequently carried
      CYP1A2*1C and/or *1D alleles, had higher clozapine and N-desmethylclozapine C/D
      ratios, and had higher lipid levels and HOMA-IR, compared to patients with normal
      insulin levels (p < .05). CONCLUSION: CYP1A2 variants *1C and *1D seem to be
      associated with higher serum clozapine concentrations and an increased risk of
      developing insulin and lipid elevations and insulin resistance on a given dose of
      clozapine.

PMID- 17503979
TI  - A randomized, double-blind, placebo-controlled trial of modafinil for negative
      symptoms in schizophrenia.
AB  - OBJECTIVE: Negative symptoms are core features of schizophrenia that are
      functionally debilitating, associated with poor outcomes, and resistant to
      existing pharmacotherapies. We performed a randomized, double-blind, placebo
      controlled study of modafinil, a medication approved for the treatment of
      excessive daytime sleepiness, to explore its efficacy as an adjunctive therapy
      for negative symptoms in schizophrenia. METHOD: Twenty subjects with DSM-IV
      schizophrenia or schizoaffective disorder were randomly assigned to double-blind
      treatment with modafinil or placebo for 8 weeks. The study ran from March 2002
      through March 2006. Outcome measures included the Scale for the Assessment of
      Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Clinical Global
      Impressions (CGI) scale, Quality of Life Interview, neurocognitive assessments
      (California Verbal Learning Test, Degraded Performance-Continuous Performance
      Test, Trail-Making Test B), and somatic measures (sleep, weight, side effects).
      RESULTS: Modafinil treatment was associated with a greater rate (CGI-Improvement
      [CGI-I] score < or = 3, 7/10 vs. 1/10) and degree (mean CGI-I score, 3.2 vs. 4.1)
      of global improvement at study endpoint compared with placebo. However, modafinil
      did not significantly improve global negative symptoms as measured by the total
      SANS or SANS individual global items. Modafinil did not significantly worsen
      psycho-pathology (according to the BPRS), compared with placebo, and was well
      tolerated. CONCLUSIONS: Although no effect on negative symptoms was found,
      adjunctive therapy with modafinil may result in global improvements in patients
      with schizophrenia who have prominent negative symptoms.

PMID- 17503981
TI  - Risk factors for suicide completion in borderline personality disorder: a case
      control study of cluster B comorbidity and impulsive aggression.
AB  - BACKGROUND: Borderline personality disorder is a major risk factor for suicidal
      behavior, yet prediction of suicide completion remains unclear. It has been
      proposed that impulsivity and aggression interact to increase suicide risk. Death
      by suicide in borderline personality disorder, then, may be the result of
      impulsivity, a core feature of the disorder, interacting with violent-aggressive
      tendencies. Using a case-control design, this study investigated clinical and
      behavioral risk factors for suicide completion in borderline personality
      disorder. METHOD: One hundred twenty subjects meeting DSM-IV criteria for
      borderline personality disorder, 50 controls and 70 who died by suicide between
      2001 and 2005, were investigated by means of proxy-based interviews using
      structured diagnostic instruments and personality trait assessments. RESULTS:
      Borderline personality disorder suicides had fewer psychiatric hospitalizations
      and suicide attempts than borderline personality disorder controls. Borderline
      personality disorder suicides were also more likely to meet criteria for current
      and lifetime substance dependence disorders. They had higher levels of current
      and lifetime Axis I comorbidity, novelty seeking, impulsivity, hostility, and
      comorbid personality disorders, while exhibiting lower levels of harm avoidance.
      Most importantly, borderline personality disorder suicides were more likely to
      have cluster B comorbidity. Impulsivity and aggression interacted to predict
      suicide, though not after controlling for cluster B comorbidity. CONCLUSIONS:
      Borderline personality disorder individuals who die by suicide differ from those
      borderlines typically encountered in acute psychiatric settings. Our results
      suggest that the lethality of borderline personality disorder suicide attempts
      results from an interaction between impulsivity and the violent-aggressive
      features associated with cluster B comorbidity. Further, the anxious trait of
      harm avoidance appears to be protective against suicidal behavior resulting in
      death.

PMID- 17503980
TI  - Randomized, double-blind comparison of sertraline and placebo for posttraumatic
      stress disorder in a Department of Veterans Affairs setting.
AB  - OBJECTIVE: To evaluate the efficacy of sertraline in the treatment of
      posttraumatic stress disorder (PTSD) in a Veterans Affairs (VA) clinic setting
      involving patients with predominantly combat-related PTSD. METHOD: 169 outpatient
      subjects with a DSM-III-R diagnosis of PTSD and who scored 50 or higher on Part 2
      of the Clinician-Administered PTSD Scale (CAPS-2) at the end of a 1-week placebo
      run-in period participated. Patients recruited from 10 VA medical centers were
      randomly assigned to 12 weeks of flexibly dosed sertraline (25-200 mg/day) (N =
      86; 70% with combat-related PTSD; 79% male) or placebo (N = 83; 72% combat
      related PTSD; 81% male) between May 1994 and September 1996. The primary efficacy
      measures were the mean change in CAPS-2 total severity score from baseline to
      endpoint, in the total score from the Impact of Event Scale, and in the Clinical
      Global Impressions-Severity of Illness and Improvement scales. RESULTS: There
      were no significant differences between sertraline and placebo on any of the
      primary or secondary efficacy measures at endpoint. In order to understand the
      results, gender, duration of illness, severity of illness, type of trauma, and
      history of alcohol/substance abuse were explored as potential moderators of
      outcome, but no consistent effects were uncovered. Sertraline was well tolerated,
      with 13% of patients discontinuing due to adverse events. CONCLUSION: Sertraline
      was not demonstrated to be efficacious in the treatment of PTSD in the VA clinic
      settings studied.

PMID- 17503982
TI  - Randomized controlled trial of cognitive behavioral social skills training for
      older people with schizophrenia: 12-month follow-up.
AB  - OBJECTIVE: There is an increasing need for empirically validated psychotherapy
      interventions that improve functioning in older people with schizophrenia. We
      developed a 24-session weekly group therapy intervention labeled Cognitive
      Behavioral Social Skills Training (CBSST), which combined cognitive-behavioral
      therapy with social skills and problem-solving training to improve functioning.
      METHOD: We previously reported end-of-treatment findings from a randomized
      controlled trial that compared treatment as usual (TAU) with TAU plus group CBSST
      in 76 outpatients, 42 to 74 years of age, with schizophrenia or schizoaffective
      disorder (DSM-IV criteria). Twelve-month follow-up results of that trial
      (conducted from October 1999 to September 2004) are reported here. Blind raters
      obtained assessments of CBSST skill mastery, functioning, psychotic and
      depressive symptoms, and cognitive insight (belief flexibility). RESULTS: The
      significantly greater skill acquisition and self-reported performance of living
      skills in the community seen in CBSST versus TAU patients at the end of treatment
      were maintained at 12-month follow-up (p < or = .05). Participants in CBSST also
      showed significantly greater cognitive insight at the end of treatment relative
      to TAU, but this improvement was not maintained at follow-up. The treatment-group
      effect was not significant for symptoms at any assessment point; however,
      symptoms were not the primary treatment target in this stable outpatient sample.
      CONCLUSION: Older people with very chronic schizophrenia were able to learn and
      maintain new skills with CBSST and showed improved self-reported functioning 1
      year after the treatment ended. Longer treatment and/or booster sessions may be
      required to maintain gains in cognitive insight.

PMID- 17503983
TI  - Natural course of bulimia nervosa and of eating disorder not otherwise specified:
      5-year prospective study of remissions, relapses, and the effects of personality
      disorder psychopathology.
AB  - OBJECTIVE: To examine prospectively the natural course of bulimia nervosa and
      eating disorder not otherwise specified (EDNOS) and to test for the effects of
      personality disorder psychopathology on remission and relapse. METHOD: Subjects
      were 92 female patients with current bulimia nervosa (N = 23) or EDNOS (N = 69)
      at baseline enrollment in the Collaborative Longitudinal Personality Disorders
      Study. Axis I psychiatric disorders (including eating disorders) were assessed
      with the Structured Clinical Interview for DSM-IV Axis I Disorders-Patient
      Version, and personality disorders were assessed with the Diagnostic Interview
      for DSM-IV Personality Disorders (DIPD-IV). The course of eating disorders was
      assessed with the Longitudinal Interval Follow-Up Evaluation and the course of
      personality disorders with the Follow-Along version of the DIPD-IV at 6 and 12
      months and then yearly through 60 months. The study was conducted from July 1996
      through June 2005. RESULTS: Probability of remission by 60 months was 74% for
      bulimia nervosa and 83% for EDNOS, and probability of relapse among those with a
      remission was 47% for bulimia nervosa and 42% for EDNOS. Patients with and
      without personality disorders did not differ in probability of remission. Cox
      proportional hazards regression analyses revealed that bulimia nervosa and EDNOS
      did not differ significantly in time to remission and that personality disorder
      comorbidity did not significantly predict time to remission. Analyses using
      proportional hazards regression with time-varying covariates revealed that
      dimensional changes in personality disorders were minimally related to either
      remission or relapse in these eating disorders. CONCLUSIONS: The 5-year natural
      course of bulimia nervosa and EDNOS differed little with both eating disorder
      categories showing similar patterns of remissions and relapses. These findings
      suggest the clinical significance of EDNOS and the need for further research on
      this most common but least studied eating disorder. The natural course of bulimia
      nervosa and EDNOS does not appear to be influenced significantly by the presence,
      severity, or time-varying changes of co-occurring personality disorder
      psychopathology.

PMID- 17503984
TI  - Prediction of response to paroxetine and venlafaxine by serotonin-related genes
      in obsessive-compulsive disorder in a randomized, double-blind trial.
AB  - OBJECTIVE: Serotonin reuptake inhibitors (SRIs) are the most effective
      pharmacologic treatment currently available for patients with obsessive
      compulsive disorder (OCD). Still, up to 40% to 60% of OCD patients do not respond
      to SRI treatment. The purpose of the present study was to determine whether
      polymorphisms of the serotonin transporter (5-HTT), 5-HT1B, and 5-HT2A receptor
      genes affect the efficacy of SRI treatment in OCD. METHOD: 91 outpatients with
      OCD according to DSM-IV criteria consented to the study and were randomly
      assigned in a 12-week, double-blind trial to receive dosages titrated upward to
      300 mg/day of venlafaxine or 60 mg/day of paroxetine. Primary efficacy was
      assessed by the change from baseline on the Yale-Brown Obsessive Compulsive Scale
      (YBOCS), and response was defined as a > or = 25% reduction on the YBOCS.
      Responders and nonresponders were stratified according to 5-HTT, 5-HT1B, and 5
      HT2A genotypes and differentiated in paroxetine-or venlafaxine-treated groups.
      The study was conducted from August 1998 to July 2002. RESULTS: In the whole
      group, 64% of responders carried the S/L genotype of the 5-HTTLPR polymorphism
      (chi2 = 7.17, df = 2, p = .028). In the paroxetine-treated patients, the majority
      of responders carried the G/G genotype of the 5-HT2A polymorphism (chi2 = 8.66,
      df = 2, p = .013), whereas in the venlafaxine-treated patients, the majority of
      responders carried the S/L genotype of the 5-HTTLPR polymorphism (chi2 = 9.72, df
      = 2, p = .008). CONCLUSIONS: The results of this study suggest that response in
      venlafaxine-treated OCD patients is associated with the S/L genotype of the 5
      HTTLPR polymorphism and in paroxetine-treated OCD patients with the G/G genotype
      of the 5-HT2A polymorphism.

PMID- 17503985
TI  - Disrupted antioxidant enzyme activity and elevated lipid peroxidation products in
      schizophrenic patients with tardive dyskinesia.
AB  - BACKGROUND: Free radical-mediated pathology has been implicated in the
      development of tardive dyskinesia (TD). Antioxidant defense system alterations
      and increased lipid peroxidation have been postulated as a possible mechanism for
      neuronal damage associated with TD. However, the relationship between antioxidant
      enzymes, lipid peroxidation products, and the severity of TD symptoms has not
      been determined within a single patient group. METHOD: Plasma levels of
      malondialdehyde (MDA), a marker of lipid peroxidation, superoxide dismutase,
      glutathione peroxidase, and catalase were examined in 80 patients with
      schizophrenia (DSM-IV criteria) and TD (Schooler-Kane criteria) and 45
      schizophrenia patients without TD. Results were compared to those of 50 age-, sex
      , and smoking status-matched controls. Tardive dyskinesia severity was assessed
      using the Abnormal Involuntary Movement Scale, and patient psychopathology was
      assessed using the Positive and Negative Syndrome Scale. RESULTS: Patients with
      TD had lower plasma superoxide dismutase, glutathione peroxidase, and catalase
      levels but higher MDA levels than those without TD. In the patients with TD, MDA
      levels were positively correlated with Abnormal Involuntary Movement Scale total
      score and with Positive and Negative Syndrome Scale negative subscore. Superoxide
      dismutase and catalase activities were inversely correlated with MDA levels.
      CONCLUSIONS: Our data support the hypothesis that oxidative stress is involved in
      the patho-physiology of TD. These data also suggest a relationship between
      oxidative stress and the severity of dyskinesia in TD patients. Increased lipid
      peroxidation may likely be a result of decreased endogenous antioxidant enzyme
      activities in TD.

PMID- 17503986
TI  - Duloxetine treatment of dysthymia and double depression: an open-label trial.
AB  - BACKGROUND: Although not as common as major depressive disorder, dysthymia is not
      rare and is associated with substantial impairment. Antidepressants and some
      psychotherapies are often effective. We explored the efficacy of the
      antidepressant duloxetine, a serotonin and norepinephrine reuptake inhibitor.
      METHOD: Between February 2005 and April 2006, we recruited 24 adults with DSM-IV
      dysthymia or dysthymia and concurrent major depression ("double depression") who
      had an entry score of > or = 17 on the clinician-rated Inventory for Depressive
      Symptomatology (IDS-C). We excluded subjects with significant medical illnesses
      and those requiring other psychotropic agents or undergoing psychotherapy.
      Subjects received duloxetine 60 mg/day for 6 weeks, increased as tolerated to 120
      mg/day for the remainder of the 12-week trial for those with an inadequate
      treatment response. RESULTS: The subjects' mean +/- SD IDS-C scores decreased
      significantly from baseline (27.3 +/- 6.3) to endpoint (7.8 +/- 7.4, Student t =
      12.38, df = 23, p < or = .001). The IDS-C response rate (intent-to-treat [ITT])
      was 83% (20/24); the remission rate (ITT) was 79% (19/24). Among study
      completers, these rates were 89% (17/19) and 84% (16/19). Five subjects (21%)
      discontinued for side effects. CONCLUSION: Duloxetine appears to be an effective
      and well-tolerated treatment for dysthymia and double depression. A double-blind,
      placebo-controlled study is under way. If duloxetine is found to be effective,
      studies powered to detect potential, clinically important differences between
      duloxetine and other antidepressants will be needed. CLINICAL TRIALS
      REGISTRATION: ClinicalTrials.gov identifier NCT00185575.

PMID- 17503988
TI  - Impact of severity of substance use disorder on symptomatic and functional
      outcome in young individuals with first-episode psychosis.
AB  - OBJECTIVE: To investigate whether severity of substance use disorder is
      independently associated with 15-month symptomatic or functional outcome in young
      individuals with first-episode psychosis. METHOD: Ninety-two individuals aged 15
      to 30 years with first-episode psychosis participated in a 15-month prospective
      follow-up study. DSM-IV criteria were used to diagnose psychotic disorders, and
      DSM-III-R criteria were used to diagnose substance use disorder (abuse or
      dependence). Measures of outcome included severity of positive and negative
      symptoms, quality of life, and level of social functioning. Data were collected
      between March and July 2001 at a specialist first-episode psychosis service and
      between January and December 1997 at 2 generic mental health services. RESULTS:
      Multiple linear regression showed that heavy substance use disorder was
      significantly associated with more severe positive symptoms at 15 months after
      controlling for the effects of gender, duration of untreated psychosis, and
      medication adherence (vs. no substance use disorder, p = .006; vs. mild substance
      use disorder, p = .023). Heavy substance use disorder was also significantly
      associated with poorer social functioning at 15 months after controlling for the
      effects of gender, duration of untreated psychosis, medication adherence, and
      positive symptoms (vs. no substance use disorder, p = .025; vs. mild substance
      use disorder, p = .047). Heavy substance use disorder was not associated with
      negative symptoms or quality of life after controlling for the effects of
      potential confounding variables. CONCLUSION: Heavy but not mild substance use
      disorder appears to be independently associated with poorer symptomatic and
      functional outcome in young patients with first-episode psychosis.

PMID- 17503989
TI  - Regular daily smoking among 14-year-old adolescents increases the subsequent risk
      for suicide: the Northern Finland 1966 Birth Cohort Study.
AB  - OBJECTIVE: To investigate the relationship between adolescent regular daily
      smoking and later suicides in a prospective longitudinal birth cohort setting.
      METHOD: Data from the Northern Finland 1966 Birth Cohort Study (N = 10,934) were
      linked with national death certificates from Statistics Finland. The information
      on suicide attempts until the end of 2001 was gathered from the Finnish Hospital
      Discharge Register (FHDR). The information on adolescent regular daily smoking
      was gathered via a questionnaire in 1980 and 1981, when the subjects were age 14
      years. RESULTS: Of all cohort males who smoked regularly at age 14 years, 2.6%
      committed suicide by age 34 years, while the corresponding proportion was 0.8%
      among experimental smokers and 0.4% among non-smokers (chi2 = 15.8, df = 2, p <
      .001). After adjusting for sociodemographic factors in adolescence and
      psychiatric morbidity, regular smokers were at a 4.05-fold hazard (95% CI = 1.18
      to 13.93, p = .026) for committing suicide at a younger age. Corresponding
      associations were not found among females. The choice of suicide method was not
      associated with smoking habits in adolescence. Furthermore, the proportion of
      suicide attempts was significantly higher among regular daily smokers, among both
      boys (3.3% vs. 1.2%) and girls (4.2% vs. 1.2%), compared with other adolescents.
      CONCLUSION: At the epidemiologic level, adolescent regular smoking was found to
      be associated with increased risk for suicide among males before the age of 34
      years. Further studies are needed to investigate the effects of smoking on
      neurobiology of depression, self-damaging aggression, and impulsive behavior.

PMID- 17503990
TI  - Double-blind, placebo-controlled trial of divalproex monotherapy in the treatment
      of symptomatic youth at high risk for developing bipolar disorder.
AB  - OBJECTIVE: To determine if divalproex sodium was superior to placebo in the
      treatment of symptomatic youths who suffer from a bipolar spectrum disorder and
      who also have a parent with a diagnosis of a bipolar illness. METHOD: Youths,
      ages 5 to 17 years, meeting DSM-IV criteria for bipolar disorder not otherwise
      specified (NOS) or cyclothymia who also had at least 1 biological parent with
      bipolar illness were randomly assigned in a double-blind fashion to receive
      treatment with either dival-proex sodium or placebo for up to 5 years. Study
      participation ended if the subject required additional clinical intervention, if
      the patient developed treatment-related adverse events, or if the participant was
      not adherent with study procedures. The primary outcome measure was time to study
      discontinuation for any reason. The study was conducted from August 1997 to April
      2003. RESULTS: Fifty-six youths with a mean (SD) age of 10.7 (3.1) years were
      randomly assigned and received either divalproex sodium (N = 29) or placebo (N =
      27). In spite of statistical power of 80% to detect hazard ratios of 2.2 or
      larger, the treatment groups did not significantly differ in survival time for
      discontinuation for any reason (p = .93) or discontinuation due to a mood event
      (p = .55). Changes in mood symptom ratings and psychosocial functioning from
      baseline to study discontinuation did not differ between groups (most significant
      p > .14). However, both groups did show improvements in mood symptoms and
      psychosocial functioning over time (all p values < .002). One patient, from the
      placebo group, ended study participation due to an adverse event. CONCLUSION:
      These results suggest that, although well tolerated, divalproex sodium does not
      produce clinically meaningful improvements in the treatment of symptomatic youths
      suffering from either bipolar NOS or cyclothymia who are at genetic risk for
      developing bipolar disorder.

PMID- 17503991
TI  - A 12-week single-blind trial of quetiapine for the treatment of mood symptoms in
      adolescents at high risk for developing bipolar I disorder.
AB  - OBJECTIVE: To investigate the effectiveness and tolerability of quetiapine for
      the treatment of adolescents at high risk for developing bipolar I disorder.
      METHOD: Twenty adolescents (aged 12-18 years) with mood symptoms that did not
      meet DSM-IV-TR criteria for bipolar I disorder and who had at least one first
      degree relative with bipolar I disorder were recruited from August 2003 to June
      2005 to participate in a single-blind, 12-week prospective study of quetiapine.
      Subjects were diagnosed using the Washington University in St. Louis Kiddie
      Schedule of Affective Disorders and Schizophrenia and were symptomatic, defined
      by a Young Mania Rating Scale (YMRS) score > or = 12 or a Childhood Depression
      Rating Scale-Revised Version (CDRS-R) score > or = 28 at baseline. The primary
      effectiveness measure was an endpoint Clinical Global Impressions-Improvement
      scale (CGI-I) score < or = 2 ("much" or "very much" improved). Secondary efficacy
      measures included change from baseline to endpoint in YMRS and CDRS-R scores.
      RESULTS: Mood disorder diagnoses in the adolescents consisted of bipolar disorder
      not otherwise specified (N = 11), dysthymia (N = 3), bipolar II disorder (N = 3),
      cyclothymia (N = 2), and major depressive disorder (N = 1). The majority of
      patients (N = 12, 60%) were non-responders to previous trials of psychotropic
      agents. Fifteen subjects (75%) completed all study visits. Eighty-seven percent
      of patients were responders (CGI-I < or = 2) to quetiapine at week 12 (mean +/-
      SD endpoint dose = 460 +/- 88 mg/day). YMRS scores decreased from 18.1 +/- 5.5 at
      baseline to 8.7 +/- 7.9 at endpoint (p < .0001), and CDRS-R scores decreased from
      38.2 +/- 9.8 to 27.7 +/- 9.3, (p = .0003). The most frequently reported adverse
      events were somnolence, headache, musculoskeletal pain, and dyspepsia. No
      subjects discontinued study participation due to adverse events. CONCLUSION:
      Although these findings are limited by the small sample size and open-label
      treatment, the results suggest that quetiapine may be an effective treatment for
      mood symptoms in adolescents with a familial risk for developing bipolar I
      disorder.

PMID- 17503992
TI  - Psychopharmacology in the emergency room.

PMID- 17503993
TI  - Augmentation of clozapine treatment with aripiprazole.

PMID- 17503994
TI  - Resolution of late-onset hypomania after repair of carotid artery stenosis: a
      case of vascular hypomania.

PMID- 17503995
TI  - What do we know about insulin resistance and glucose metabolism in patients with
      schizophrenia treated with antipsychotics?

PMID- 17503998
TI  - Decreased lipoprotein lipase as a risk factor for atypical neuroleptic-induced
      hypertriglyceridemia.

PMID- 17503999
TI  - A pilot observational crossover study of QTc interval changes associated with
      switching between olanzapine and risperidone.

PMID- 17504000
TI  - A case report of reemergence of antipsychotic-induced dyskinesia with citalopram.

PMID- 17504001
TI  - Aripiprazole and worsening of psychosis: a case report.

PMID- 17504002
TI  - Alexandra District Ambulance Service through the eyes of a medical student.

PMID- 17504003
TI  - Being a dispensing prescriber in rural South India.

PMID- 17504004
TI  - Disease mongers in a nation in transition?

PMID- 17504005
TI  - Evaluation of ECG time intervals in a rabbit model of anthracycline-induced
      cardiomyopathy: a useful tool for assessment of cardioprotective agents.
AB  - The aim of this study was to analyze the ECG time intervals in the course of the
      development of chronic anthracycline cardiomyopathy in rabbits. Furthermore, this
      approach was employed to study the effects of a model cardioprotective drug
      (dexrazoxane) and two novel iron chelating compounds--salicylaldehyde
      isonicotinoyl hydrazone (SIH) and pyridoxal 2-chlorobenzoyl hydrazone (o-108).
      Repeated daunorubicin administration induced a significant and progressive
      prolongation of the QRS complex commencing with the eighth week of
      administration. At the end of the study, we identified a significant correlation
      between QRS duration and the contractility index dP/dt(max) (r = -0.81; P<0.001)
      as well as with the plasma concentrations of cardiac troponin T (r = 0.78;
      P<0.001). In contrast, no alterations in ECG time intervals were revealed in the
      groups co-treated with either dexrazoxane or both novel cardioprotective drugs
      (SIH, o-108). Hence, in this study, the QRS duration is for the first time shown
      as a parameter suitable for the non-invasive evaluation of the anthracycline
      cardiotoxicity and cardioprotective effects of both well established and
      investigated drugs. Moreover, our results strongly suggest that novel iron
      chelators (SIH and o-108) merit further study as promising cardioprotective drugs
      against anthracycline cardiotoxicity.

PMID- 17504007
TI  - Comparison between singleton- and triplet-specific "growth" curves to detect
      growth restricted triplet infants.
AB  - OBJECTIVE: To evaluate whether triplet- or singleton-specific growth standards
      should be used to define the growth restricted triplet fetus/neonate. STUDY
      DESIGN: We retrospectively compared the predictive values of singleton vs.
      triplet-specific "growth" standards using the neonatal ponderal index as
      reference for growth restriction. RESULTS: A ponderal index <1 SD from the mean
      was found in 356 (14.4%) of 2477 triplet infants. A total of 686 (27.7%) infants
      were small for gestational age (SGA) by singleton standards, but only 168 (6.8%)
      by triplet standards. After 31 weeks' gestation, triplet standards are
      significantly better associated with a low ponderal index (OR 2.0, 95% CI 1.1,
      3.4 at 32 weeks to OR 4.1, 95% CI 2.8, 6.3 at 36-37 weeks), resulting in better
      positive predictive value and higher specificity of triplet standards in
      predicting a low ponderal index. CONCLUSION: Triplet birth weight standards are
      better than singleton standards at >31 but not at < or =31 weeks' gestation in
      predicting a low neonatal ponderal index.

PMID- 17504008
TI  - Vacuum extraction and autonomic balance in human infants.
AB  - The impact of delivery mode on the cardiac autonomic balance was studied in a
      sample of 101 full term appropriate for gestational age (AGA) human infants.
      Cardiac autonomic balance was measured by assessing basic heart rate, and two
      indicators of vagal tone, the Root Mean Square of Successive Differences (RMSSD)
      and Standard Deviation of NN-intervals (SDNN) as two different measures of short
      term heart rate variability at 2, 6, and 16 weeks postnatal age. Sixty-seven
      infants were delivered spontaneously, 29 by cesarean section and five by vacuum
      extraction. Children delivered by vacuum extraction had a significantly lower
      basic heart rate (P=0.01), higher RMSSD (P=0.0003) and higher SDNN (P=0.0001) at
      two, but not at six and sixteen weeks, indicating a temporary elevation of
      cardiac vagal tone in these infants. These data indicate a potential transitory
      impact of vacuum extraction on autonomic balance persisting until at least two
      weeks postnatal age.

PMID- 17504009
TI  - Comparison of two- and three-dimensional ultrasonography in lung volume
      measurement of normal fetuses.
AB  - AIM: The purpose of this study was to compare the two- and three-dimensional
      methods for measuring fetal lung volume of normal fetuses. METHODS: A cross
      sectional study was performed with 51 normal pregnant women between 20 and 35
      weeks. The ellipsoid formula (X*Y*Z*0.52) was used for volume calculation with
      the two-dimensional (2D) method. With the VOCAL (Virtual Organ Computer-aided
      Analysis) method, a rotation angle of 30 degrees was used. Intraclass correlation
      coefficient (ICC), paired Student's t-test and Bland-Altman plots were used to
      compare the techniques. To calculate the intraobserver variability we used the
      ICC and compared the means between the two measures using the paired Student's p
      test. RESULTS: VOCAL and 2D methods were highly correlated (ICC=0.919 and 0.873
      for the right and left lungs, respectively), however, there was a disagreement.
      The fetal lung volume means calculated by the 2D method were always overestimated
      in relation to the means obtained by the VOCAL, for the right lung (24.02 mL x
      19.15 mL; P<0.001), as well as for the left (16.03 mL x 13.77 mL; P=0.002). As
      for the intraobserver variability, a good reproducibility was observed for the
      volume measurement of the left lung by the 2D technique (mean=0.40 mL; P=0.57)
      and by the VOCAL (mean=-0.22 mL; P=0.63). The 2D method, however, presented low
      reproducibility for the right lung (mean=1.73 mL; P=0.31). CONCLUSION: The two
      dimensional method had low agreement and low reproducibility in relation to the
      three-dimensional method for measurement of fetal lung volume in normal fetuses.

PMID- 17504010
TI  - Cell adhesion and cancer: is there a potential for therapeutic intervention?
AB  - Carcinogenesis involves a disruption in adhesion molecule expression and tissue
      architecture, and tumour invasion requires adhesion-dependent migration into
      surrounding tissues. Therefore, a variety of peptide and antibody-based reagents
      that block integrins, cadherins, immunoglobulin superfamily and selectin adhesion
      molecules have been developed to treat cancers. Therapeutics directed at adhesion
      molecules can block interactions between tumour cells, endothelial cells and
      immune cells to prevent tumour cell invasiveness and metastasis. Blocking the
      adhesion molecules that facilitate the invasion of tumours by endothelial cells
      and immune cells can prevent tumour-associated angiogenesis and the recruitment
      of immune-mediated growth factors which are required for tumour growth and
      spread. In addition, targeted therapies using anticancer agents attached to
      antibodies or peptides directed as tumour-specific adhesion molecules are being
      developed.

PMID- 17504011
TI  - The role of vasoactive intestinal peptide in neuroprotection: Professor Illana
      Gozes is interviewed by Emma Quigley.
AB  - Professor Illana Gozes was interviewed by Emma Quigley (Senior Editor, Expert
      Opinion) on 17(th) April 2007. Professor Illana Gozes BSc, PhD holds the titles
      of Professor of Clinical Biochemistry; The Lily and Avraham Gildor Chair for the
      Investigation of Growth Factors; Director of Adams Super Center for Brain Studies
      and Levi-Edersheim-Gitter fMRI Institute; Head of the Dr Diana and Zelman Elton
      (Elbaum) Laboratory for Molecular Neuroendocrinology, Tel Aviv University and
      Chief Scientific Officer, Allon Therapeutics, Inc., Vancouver BC, Canada.
      Professor Gozes has served as a member (or chair) of several faculty, university
      or national and international committees and she currently serves on the Board of
      Directors of Allon Therapeutics, the Scientific Review Board of the ISOA, and is
      the Editor-in-Chief of the Journal of Molecular Neuroscience. Professor Gozes has
      received a number of scientific awards for her work including the Landau Award
      for an excellent PhD dissertation, the Juludan Prize and the Teva Founders Prize
      for exceptional scientific studies that may lead to biotechnology developments as
      well as the Bergmann Prize and the Neufeld award for outstanding/leading US
      Israel BSF grant proposals, and has published extensively in the fields of
      molecular neuroscience and neuroprotection (> 200 scientific manuscripts). She is
      co-inventor of > 15 patents and applications, including the composition of matter
      patent on AL-108 and AL-208, Allon's lead compounds. Professor Gozes received a
      BSc from Tel Aviv University, a PhD from The Weizmann Institute of Science and
      was a Weizmann Postdoctoral Fellow at Massachusetts Institute of Technology,
      Research Associate/Visiting Scientist at the Salk Institute and the Scripps
      Clinic and Research Foundation, a Senior Scientist/Associate Professor at the
      Weizmann Institute and a Fogarty-Scholar-in-Residence at the National Institutes
      of Health (USA). Professor Gozes directs a very active research laboratory at Tel
      Aviv University and is mentoring and has mentored directly approximately 50
      graduate students toward their MSc or PhD degrees.

PMID- 17504013
TI  - Oxidative stress and steroid resistance in asthma and COPD: pharmacological
      manipulation of HDAC-2 as a therapeutic strategy.
AB  - Insensitivity to corticosteroid treatment in inflammatory conditions, such as
      asthma and chronic obstructive pulmonary disease, present considerable management
      problems and cost burdens to health services. Oxidative stress is a major
      component of chronic inflammation and can have a significant suppressive effect
      on corticosteroid efficacy. Recent advances in the understanding of both the
      mechanisms of corticosteroid action and corticosteroid insensitivity have
      provided hope for a therapeutic strategy of restoring corticosteroid sensitivity.
      Histone deacetylase 2 (HDAC-2) plays a pivotal role in corticosteroid action and
      is reduced in many cases of steroid insensitivity. Moreover, it has shown that
      oxidative stress can be responsible for this reduction in HDAC-2 activity. Two
      structurally different compounds; methyl-xanthine theophylline and polyphenol
      curcumin restore HDAC activity, thereby restoring corticosteroid function. Low,
      subbronchodilator doses of theophylline can also act as corticosteroid-sparing
      drugs in asthmatics. Although these compounds appear to restore corticosteroid
      function and may initially provide therapeutic potential, they lack specificity
      and the mechanism of their action is unknown. Once their mechanisms of action are
      established, it is likely that derivatives of these compounds may be used as a
      therapeutic strategy to restore corticosteroid insensitivity in the future.

PMID- 17504012
TI  - Retinoid-related orphan receptor gamma t is a potential therapeutic target for
      controlling inflammatory autoimmunity.
AB  - Retinoid-related orphan receptor gamma t (RORgamma t) is a member of the nuclear
      receptor family that is specifically expressed in T cell compartments. RORgamma t
      regulates the development of T cells in the thymus and the differentiation of
      effector T cells in the periphery. During T cell development, RORgamma t enhances
      CD4(+)CD8(+) double positive thymocyte survival by upregulating Bcl-x(L). In the
      periphery, RORgamma t regulates IL-17 production and dictates the differentiation
      of pro-inflammatory T helper 17 (T(H)17) cells that play a critical role in
      inflammatory conditions and autoimmunity. RORgamma t-deficient T cells fail to
      differentiate into T(H)17 cells, whereas forced expression of RORgamma t is
      sufficient to induce naive T cells to produce IL-17. T(H)17 cells are believed to
      be the major inflammatory cells in autoimmune diseases. Therefore, inhibition of
      RORgamma t activity could potentially alleviate the symptoms associated with the
      T(H)17-dependent inflammatory autoimmune diseases. RORgamma t is thus potentially
      an excellent therapeutic target for the intervention of inflammatory
      autoimmunity.

PMID- 17504014
TI  - Targeting Helicobacter pylori in gastric carcinogenesis.
AB  - Gastric infection by Helicobacter pylori is an important risk factor for the
      development of gastric cancer. Recent research has identified both bacterial and
      host factors related to increased gastric cancer risk, including virulence
      associated genes located in the cytotoxin-associated gene pathogenicity island
      and the vacuolating toxin A exotoxin, as well as polymorphisms in key cytokines
      and cytokine receptors that mediate the host's gastric inflammatory response.
      Early randomized trials indicate that eradicating H. pylori with antibiotics may
      prevent gastric cancer, although the effects so far have been modest, and are
      probably confined to individuals who had not developed preneoplastic lesions at
      the time of eradication. Targeting H. pylori to prevent gastric cancer may be
      best achieved through vaccination, better understanding of the molecular
      pathogenesis of H. pylori-associated carcinogenesis and additional
      chemopreventive strategies.

PMID- 17504015
TI  - Downstream intracellular effectors of epidermal growth factor receptor as targets
      for anticancer therapy.
AB  - In recent years, the knowledge about mutations in components of the intracellular
      signal transduction pathway has greatly improved. Pivotal target molecules, such
      as Ras, PI3K, mammalian target of rapamycin (mTOR) and PKC, form an important
      biochemical network, which, when mutated, drives cell growth in an unlimited
      manner. Cancer cells have been shown to be able to harness different growth
      factor signalling pathways. Protein kinase inhibitors, targeted to the above
      pathways, have demonstrated activity against several solid tumours and are
      generally better tolerated than standard cytotoxic agents. The future challenge
      will be to find the most clever way to use combinations of these novel compounds.

PMID- 17504016
TI  - Therapeutic potential of drugs to modulate DNA repair in cancer.
AB  - Most established cancer therapy regimes involve DNA-damaging chemotherapy or
      radiotherapy. The DNA repair capacity of the tumour, therefore, represents a
      mechanism of therapeutic resistance. Drugs to inhibit DNA repair pathways have
      been developed and they demonstrate good chemosensitisation and
      radiosensitisation activity in preclinical models. Two classes of DNA repair
      inhibitors have entered clinical trial and show promising activity. Genetic
      instability in tumours may be at least partially due to defects in DNA repair
      pathways; such defects may underlie the inherent sensitivity of some tumours to
      certain classes of anticancer agent. DNA repair defects may also make the tumour
      dependent on complimentary or back-up pathways; laboratory evidence shows that
      targeting these complimentary pathways results in tumour-selective therapy.

PMID- 17504017
TI  - Drug discovery in the metabolic syndrome: context and some recent developments.
AB  - The metabolic syndrome, encompassing the clinically distinct but related areas of
      dyslipidaemia, insulin resistance, obesity and vascular disease, offers a wide
      arena for drug discovery. There is substantial and growing unmet medical need,
      particularly as the worldwide epidemic of obesity continues to develop. There are
      also many targets and biological mechanisms that can be exploited. However, the
      context for clinical development is challenging because of the many ways in which
      the syndrome can be approached. As with most therapeutic areas, preclinical data
      provide only limited confidence in the potential of a novel target in humans. In
      this review, the author outlines the context for drug discovery in the metabolic
      syndrome, the clinical and biological scope and recent developments in
      preclinical models. Finally, existing examples of drug targets for a range of
      biological mechanisms are considered, outlining their biology and points relevant
      to lead identification and optimisation and clinical development.

PMID- 17504018
TI  - Lysine-specific demethylase 1 as a potential therapeutic target.
AB  - Chromatin is a highly dynamic structure that undergoes a variety of chemical
      modifications. These modifications mediate alterations of the chromatin
      architecture, generate binding platforms that are recognized by other proteins,
      and are important elements of epigenetic gene regulation. An array of
      antagonizing histone modifying enzymes that catalyze the attachment and removal
      of a number of chemical groups has been described and their biologic role has
      been an intense area of research. With the recent discovery of the first histone
      demethylase, lysine-specific demethylase-1, a dynamic view of histone methylation
      was born. As a deeper understanding of their involvement in transcriptional
      regulation is gained, histone demethylases are becoming increasingly interesting
      targets for drug development.

PMID- 17504019
TI  - Novel therapeutic targets for the treatment of Fabry disease.
AB  - Fabry disease is an X-linked lysosomal storage disorder resulting from deficient
      activity of alpha-galactosidase A. The traditional concept that is used to
      explain the complications of the disease involves progressive accumulation of
      globotriaosylceramide in endothelial and smooth muscle cells, resulting in
      vascular damage. Clinically, progressive renal insufficiency, cardiac involvement
      and brain pathology evolves. Two pharmaceutical companies have developed enzyme
      replacement therapy in Fabry disease. Although the first clinical trials showed
      great promise, it is clear that long-term effects are not as robust as was
      anticipated. Stabilisation of renal function and decreases in cardiac hypertrophy
      has been observed, but some patients may experience progressive complications. As
      there are recent indications that serum components contribute to the
      pathophysiology of Fabry disease, fundamental studies are needed to unravel the
      precise role and identity of these factors. Combination of these basic studies
      with clinical follow up may ultimately reveal when the 'point of no return' is
      reached. Advanced renal insufficiency seems to be a clinical indicator of lack of
      response, but other signs and symptoms are probably related to adverse outcome.
      It is anticipated that in the future controlled studies in early symptomatic or
      presymptomatic patients will be required. In addition, alternative strategies
      such as substrate reduction or chaperone therapy, either alone or in combination
      with enzyme replacement therapy, should be explored. Because Fabry disease is
      rare, collaborative efforts should be undertaken and openness of data should be
      strived for.

PMID- 17504020
TI  - The therapeutic uses of chromatin-modifying agents.
AB  - In contrast to genetic aberrations, epigenetic aberrations can be reversed by the
      use of histone acetyltransferase (HAT), histone deacetylase (HDAC), SIRT, or
      histone methyltransferase (HMT) inhibitors. A well-known HDACi, suberoylanilide
      hydroxamic acid, has been recently approved for the treatment of cutaneous T cell
      lymphoma, and a number of HDACi are in clinical trials as anticancer drugs. In
      addition, HDACi could be useful in antimalarial and antifungal therapies and can
      reactivate the HIV-1 expression in latent cellular reservoirs, thus suggesting
      the use in a combination therapy with highly active antiretroviral therapy. HDACi
      have also been reported to have anti-inflammatory effects through inhibition of
      cytokines and key transcription factors, and to ameliorate the phenotypes in
      animal models of neurological disorders. HDACi can also reactivate the gamma
      globin gene for the treatment of beta-thalassaemia, and recently were shown to
      relieve morphological and functional effects of muscular dystrophia. Dysfunction
      of HAT enzymes is also often associated with several diseases, including cancer;
      thus, the HATi can represent new chemical entities for the development of new
      drugs. Only a few HMTi have been described to date, but these small molecules
      could be a useful scaffold to discovering new highly active and enzyme-selective
      compounds to develop as therapeutics.

PMID- 17504021
TI  - Inflammatory bowel diseases: meeting of the European Crohn's Colitis
      Organization, 1-3 March 2007, Innsbruck, Austria.
AB  - Inflammatory bowel diseases affect > 1 million Europeans, and mostly people at a
      young age. Although these diseases are still increasing worldwide, especially in
      children and adolescents, progress in the pathophysiology and treatment of these
      diseases in recent years has been tremendous. In particular, anti-TNF-alpha
      agents dramatically changed the management of these diseases. The European
      Crohn's Colitis Organization recently held its second annual meeting in
      Innsbruck, Austria dealing with both new basic and clinical developments in the
      field.

PMID- 17504023
TI  - MicroRNAs as cancer players: potential clinical and biological effects.
AB  - MicroRNAs (miRNAs) are nonprotein-coding RNAs that function as
      posttranscriptional gene regulators. They can regulate their targets directly by
      mRNA cleavage or by repressing their translation, depending on the degree of
      complementariety between the miRNA and the target. Recent evidences have shown
      that miRNA control cell growth, apoptosis, and differentiation. Moreover, miRNA
      expression correlates with cancers and could have a crucial function in tumor
      progression. Bioinformatic data indicates that each miRNA can control hundreds of
      target genes, but identification of the accurate miRNA targets will be crucial to
      exploit the emerging knowledge of miRNA contribution to cancer process. While the
      miRNA field is still emerging, the benefit of our understanding of miRNA in
      cancer is potentially enormous, especially if we are able to apply this knowledge
      to provide new therapies for patients.

PMID- 17504024
TI  - Unique MicroRNA signature and clinical outcome of cancers.
AB  - MicroRNAs (miRNAs) are endogenous small non-protein-coding RNAs (18-25
      nucleotides) that conduct the post-transcriptional repression of hundreds of
      their target proteins. They regulate many kinds of basic cellular processes
      including proliferation, differentiation, stress response, and cell death. Recent
      evidence has shown that deregulation of miRNAs correlates with certain features
      of diverse cancers (such as tumorigenesis, differentiation status, and outcome of
      tumor patients), and indicates that miRNAs can act as oncogenes or tumor
      suppressors. Here, we summarize these recent studies and provide a new
      perspective on understanding the role of miRNAs in initiation and progression of
      cancers. We also discuss the future applications of miRNAs in diagnostic and
      prognostic implications of cancers.

PMID- 17504025
TI  - miRNA profiling for diagnosis and prognosis of human cancer.
AB  - MicroRNAs (miRNAs) are a recently discovered class of small (approximately 18-24
      nt) nucleic acids that negatively regulate gene expression. This novel class of
      molecules modulates a wide array of growth and differentiation processes in human
      cancers. High throughput analyses, utilizing the solid phase, array platform, or
      liquid phase, bead-based hybridization have variously demonstrated that miRNA
      expression was commonly dysregulated in human cancer. miRNA expression profiling
      has shown promise in defining malignant status in retrospective studies.
      Considerable disagreement remains with respect to the miRNA signature for a
      specific cancer cell type, which appears to depend largely on the analytical
      platform. Nonetheless, various internally controlled studies have successfully
      identified the histotype of tumors of unknown origin according to miRNA
      expression profile. The evaluation of miRNAs expression may also be of prognostic
      value, as best exemplified by the correlation of let-7 and mir-155 levels with
      disease survival in nonsmall cell lung cancer.

PMID- 17504028
TI  - MicroRNA detection and target prediction: integration of computational and
      experimental approaches.
AB  - In recent years, microRNAs (miRNAs), a class of 19-25 nucleotides noncoding RNAs,
      have been shown to play a major role in gene regulation across a broad range of
      metazoans and are important for a diverse biological functions. These miRNAs are
      involved in the regulation of protein expression primarily by binding to one or
      more target sites on an mRNA transcript and causing cleavage or repression of
      translation. Computer-based approaches for miRNA gene identification and miRNA
      target prediction are being considered as indispensable in miRNA research.
      Similarly, effective experimental techniques validating in silico predictions are
      crucial to the testing and finetuning of computational algorithms. Iterative
      interactions between in silico and experimental methods are now playing a central
      role in the biology of miRNAs. In this review, we summarize the various
      computational methods for identification of miRNAs and their targets as well as
      the technologies that have been developed to validate the predictions.

PMID- 17504026
TI  - MicroRNA and brain tumors: a cause and a cure?
AB  - Malignant brain tumors, including high-grade gliomas, are among the most lethal
      of all cancers. Despite considerable advances, including multi-modal treatments
      with surgery, radiotherapy, and chemotherapy, the overall prognosis remains
      dismal for patients diagnosed with these tumors. With the discovery of RNA
      interference (RNAi) for target-specific gene silencing via small interfering RNA
      (siRNA), a novel method to target malignant gliomas has been exposed, an endeavor
      that is aggressively being carried out in numerous laboratories. However,
      practical difficulties in tissue- or organ-specific targeting of therapeutic
      quantities of siRNA still preclude its applicability in a clinical setting.
      MicroRNA (miRNA), an endogenously expressed form of siRNA, not only presents an
      alternate method to induce RNAi in a given diseased tissue or organ, but also
      exposes a unique set of diagnostic markers that can be used to identify, and then
      differentiate between tumor grades. Thus, miRNA can be considered the cells'
      answer to siRNA. Discovered over a decade ago, miRNA is fast becoming recognized
      as crucial in regulating gene expression in cancers. Therein lies the therapeutic
      potential of miRNA, as it may now be possible to induce or inhibit RNAi in a
      given diseased cell population by controlling the cells' miRNA expression
      profile. This review outlines the potential of miRNA as a therapeutic strategy
      against high-grade gliomas, and also the technological hurdles that need to be
      addressed before this promising technique can be administered in a clinical
      setting.

PMID- 17504027
TI  - MicroRNA-143 and -145 in colon cancer.
AB  - MicroRNAs (miRNAs) are endogenous, small non-coding RNAs (20-22 nucleotides) that
      negatively regulate gene expression at the translational level by base pairing to
      the 3' untranslated region of target messenger RNAs. More than 400 miRNAs have
      been identified in humans and are evolutionally conserved from plants to animals.
      It has been revealed that miRNAs regulate various biological processes, such as
      development, cell differentiation, cell proliferation, and cell death. It is
      predicted that 30% of protein-encoding genes are regulated by miRNAs.
      Inappropriate expression of miRNAs has been found in cancer. Especially, the
      expression level of miRNAs that act like anti-oncogenes is frequently reduced in
      cancers because of chromosome aberrations. In addition, since the processing of
      miRNAs has been characterized to be enzymatic in nature, the expression levels of
      miRNAs are closely associated with the activity and levels of such enzymes. In
      this review, we discuss recent remarkable advances in miRNA biogenesis, bio
      networking involving miRNAs, and their roles in carcinogenesis. Further, we
      discuss the expression of miRNA-143 and -145 in colon cancer and their roles in
      carcinogenesis. The available data suggest that miRNAs would be potentially
      useful as diagnostic and therapeutic tools.

PMID- 17504029
TI  - Principles and limitations of computational microRNA gene and target finding.
AB  - In 2001 there were four PubMed entries matching the word "microRNA" (miRNA).
      Interestingly, this number has now far exceeded 1300 and is still rapidly
      increasing. This more than anything demonstrates the extreme attention this field
      has had within a short period of time. With the large amounts of sequence data
      being generated, the need for analysis by computational approaches is obvious.
      Here, we review the general principles used in computational gene and target
      finding, and discuss the strengths and weaknesses of the methods. Several methods
      rely on detection of evolutionary conserved candidates, but recent methods have
      challenged this paradigm by simultaneously searching for the gene and the
      corresponding target(s). Whereas the early methods made predictions based on sets
      of hand-derived rules from precursor-miRNA structure or observed target-miRNA
      interactions, recent methods apply machine learning techniques. Even though these
      methods are already powerful, the amount of data they rely on is still limited.
      Since it is evident that data are continuously being generated, it must be
      anticipated that these methods will further improve their performance.

PMID- 17504030
TI  - Bio-informatic trends for the determination of miRNA-target interactions in
      mammals.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate mRNAs through
      a sequence-specific mechanism. By virtue of their structure and mechanism of
      action, computational methods have been devised to investigate the encoding of
      miRNA genes and the targets of miRNA action. A variety of assumptions have
      predicated the implementation of these various computational solutions.
      Evolutionary sequence conservation, secondary structure, and folding energetics
      are some of the assumptions that have been used. The success of these different
      computational solutions has been evaluated for both elucidation of new miRNAs and
      deducing targets of miRNA action. While the focus is on search techniques for new
      miRNAs, we have compared the programs miRseeker, miRScan, PalGrade, ProMiR, and
      miRAlign as examples of implementation of these techniques. For these programs, a
      benchmark comparison between theoretical estimation and actual identification is
      possible. We have also compared the target prediction programs TargetScanS,
      PicTar, DIANA-microT, miRanda, and RNAhybrid. However, it is difficult to
      rigorously assess the benchmark performance of these programs due to the
      difficulty in confirming their theoretical predictions.

PMID- 17504033
TI  - Mounting expectations for Thoroughbred stallions.

PMID- 17504034
TI  - What is your diagnosis? Metastatic bone tumor.

PMID- 17504035
TI  - What is your diagnosis? Esophageal cyst.

PMID- 17504036
TI  - Theriogenology question of the month. Abscess in the left hemiscrotum, septic
      urethritis, and inflammation of the right vas deferens.

PMID- 17504037
TI  - Veterinary expertise in biosecurity and biological risk assessment.

PMID- 17504038
TI  - Enhancing nontechnical skills, knowledge, aptitudes, and attitudes through
      veterinary leadership development programs.

PMID- 17504039
TI  - Serum chemistry alterations in Alaskan sled dogs during five successive days of
      prolonged endurance exercise.
AB  - OBJECTIVE: To determine the impact of successive days of endurance exercise on
      select serum chemistry values in conditioned Alaskan sled dogs. DESIGN:
      Prospective cohort study. ANIMALS: 10 conditioned Alaskan sled dogs. PROCEDURES:
      All dogs ran 160 km/d for 5 consecutive days. Serum was obtained prior to
      exercise and immediately after each exercise run; all samples were obtained
      before dogs were fed. Serum electrolyte, mineral, protein, total bilirubin, urea
      nitrogen, creatinine, and cardiac troponin-I concentrations and serum alkaline
      phosphatase, alanine aminotransferase, creatine kinase, and aspartate
      aminotransferase activities were measured. Data were analyzed by means of
      analysis of covariance for a randomized complete block design with dog as a
      blocking variable, time as a covariate, and distance run as the treatment of
      interest. Least square mean values were compared with values obtained prior to
      exercise, and linear and quadratic contrasts were examined. RESULTS: Serum
      globulin concentration was low prior to exercise (mean +/- SD, 2.2 +/- 0.3g/dL)
      and progressively decreased as exercise continued. Exercise was associated with
      increases in serum chloride, urea nitrogen, and cardiac troponin-I concentrations
      and serum alanine aminotransferase, creatine kinase, and aspartate
      aminotransferase activities and with progressive decreases in serum potassium,
      total protein, and albumin concentrations. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggested that multiple successive days of endurance exercise resulted in
      mild aberrations in serum chemistry variables in conditioned sled dogs. Changes
      likely reflected the metabolic stresses of prolonged endurance exercise as well
      as dietary composition. Hypoglobulinemia in resting, conditioned sled dogs may
      reflect the immunosuppressive or catabolic effects of intense endurance training.

PMID- 17504040
TI  - Community-acquired infectious pneumonia in puppies: 65 cases (1993-2002).
AB  - OBJECTIVE: To identify causative organisms, treatment, outcome, and prognosis for
      dogs < 1 year old with community-acquired infectious pneumonia. DESIGN:
      Retrospective case series. ANIMALS: 65 dogs. PROCEDURES: Dogs were considered to
      have community-acquired infectious pneumonia if they had clinical signs of
      primary respiratory tract disease in conjunction with radiographic evidence of
      alveolar disease and positive results following bacterial culture of tracheal
      wash fluid. RESULTS: Most dogs were hypoxemic at the time of initial examination,
      with pulmonary function becoming worse during the first few days of
      hospitalization before improving; 57 (88%) dogs survived to discharge. Bordetella
      bronchiseptica was isolated from tracheal wash fluid from 32 (49%) dogs, and
      other organisms, predominantly gram-negative enteric bacteria, were isolated from
      the other 33 (51%). Dogs with Bordetella pneumonia were significantly younger
      (median, 14 vs 21 weeks), were significantly more likely to have been obtained
      from a pet store (19/31 vs 7/32), had been owned for a significantly shorter time
      prior to the onset of illness (median, 18 vs 90 days), had significantly higher
      PvCO2 values at initial examination (median, 48.7 vs 41.3 mm Hg), were
      significantly more likely to receive supplemental oxygen (25/32 vs 16/33), and
      had significantly longer hospitalization times (mean, 7.2 vs 4.9 days) than did
      dogs with pneumonia caused by any other organism. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that a type of community-acquired infectious
      pneumonia could be identified in dogs < 1 year old, with disease being more
      severe in dogs with Bordetella pneumonia than in dogs with pneumonia caused by
      other bacterial organisms.

PMID- 17504041
TI  - Osteochondral fragments involving the dorsomedial aspect of the proximal
      interphalangeal joint in young horses: 6 cases (1997-2006).
AB  - OBJECTIVE: To determine clinical and diagnostic imaging findings in young horses
      with osteochondral fragments involving the dorsomedial aspect of the proximal
      interphalangeal (PIP) joint. DESIGN: Retrospective case series. ANIMALS: 6
      horses. PROCEDURES: Medical records were reviewed. Follow-up information was
      obtained through telephone conversations with owners or trainers or by examining
      race records. RESULTS: Horses were between 1 and 4 years old. Three had bilateral
      osteochondral fragments in the forelimbs (n = 2 horses) or hind limbs (1).
      Radiographically, all but 1 fragment seemed to originate from the dorsomedial
      aspect of the distal end of the first phalanx. Fragment size ranged from 6 x 9 mm
      to 11 x 21 mm. Three horses had lameness referable to the region of the affected
      joint; the other 3 horses did not have clinical signs referable to affected PIP
      joints. Two horses were euthanized shortly after diagnosis at the owners' request
      because of concerns that the horses would be unsuited for their intended athletic
      use. Two of the 3 horses in which fragments were incidental findings were able to
      race successfully, although 1 received intra-articular corticosteroid treatments;
      the third was retired because of unrelated orthopedic problems. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that osteochondral fragments involving the
      dorsomedial aspect of the PIP joint may be an incidental finding in young horses.
      Given the absence of clinical signs in 5 of 9 affected joints and the fact that 3
      of 6 horses were affected bilaterally, a developmental origin of the fragments
      was suspected.

PMID- 17504042
TI  - Survival rate and short-term fertility rate associated with the use of fetotomy
      for resolution of dystocia in mares: 72 cases (1991-2005).
AB  - OBJECTIVE: To determine survival rate, complications, and short-term fertility
      rate after fetotomy in mares. DESIGN: Retrospective study. ANIMALS: 72 mares with
      severe dystocia. PROCEDURES: Records from 1991 to 2005 were searched for mares
      with dystocia in which a fetotomy was performed. Data relating to presentation
      and position of foals; survival rate, complications, and short-term fertility
      rate in mares; and 45-day pregnancy rate in mares bred 2 to 3 months after
      fetotomy were recorded. RESULTS: Anterior fetal presentation was detected for 54
      of 72 (75%) mares, posterior presentation was detected for 13 (18.1%), and
      transverse presentation was detected for 5 (6.9%). One fetus in anterior
      presentation was hydrocephalic. Survival rate after fetotomy was 95.8%.
      Complications included retained fetal membranes (5.5%), laminitis (6.9%), vaginal
      and cervical lacerations (2.8%), and delayed uterine involution (2.8%). Mares
      bred 2 to 3 months after fetotomy had good short-term fertility, with a mean
      pregnancy rate of 79.4% at 45 days after breeding. CONCLUSIONS AND CLINICAL
      RELEVANCE: The survival rate was high, compared with rates reported after
      cesarean section, and short-term fertility rate was similar to those reported for
      mares that had a controlled vaginal delivery or cesarean section. Fetotomy
      performed by a skilled veterinarian on a nonviable fetus should be considered as
      a means of quick and safe correction of dystocia that does not necessarily impair
      short-term fertility in affected mares.

PMID- 17504043
TI  - Long-term outcome associated with intratumoral chemotherapy with cisplatin for
      cutaneous tumors in equidae: 573 cases (1995-2004).
AB  - OBJECTIVE: To determine outcome associated with cutaneous tumors treated via
      intratumoral chemotherapy with cisplatin and identify risk factors affecting
      local tumor control and complications in equidae. DESIGN: Retrospective case
      series. ANIMALS: 573 equidae with 630 cutaneous tumors. PROCEDURES: Medical
      records of horses, mules, donkeys, and ponies with cutaneous tumors treated via
      intratumoral chemotherapy with cisplatin were analyzed. RESULTS: 549 horses, 13
      mules, 8 donkeys, and 3 ponies with 630 histologically confirmed cutaneous tumors
      were included. Tumors included sarcoids (n = 409), squamous cell carcinomas
      (151), soft tissue sarcomas (28), cutaneous lymphomas (26), and melanomas (16).
      Overall cure rate, defined as local control at 4 years, was 93.3%. For all tumor
      stages combined, cure rates after 1 course of treatment were 96.3% for sarcoids,
      96% for lymphomas, 88% for squamous cell carcinomas, 85% for soft tissue
      sarcomas, and 81% for melanomas. Treatment protocol, tumor stage, and prior
      treatment were significant prognostic factors for tumor control. Treatment
      efficacy was lower for large tumors, those with gross postoperative residual
      disease, and those that had been treated previously with other modalities.
      Treatment was well tolerated. Local reactions were more likely to occur and to be
      more severe after the third and fourth treatment sessions. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results confirmed the value of intratumoral chemotherapy with
      cisplatin for treatment of cutaneous tumors in equidae. The results cannot be
      extrapolated to other formulations of cisplatin or other protocols that might be
      used.

PMID- 17504045
TI  - Prevalence of Mycoplasma bovis in backgrounding and stocker cattle operations.
AB  - OBJECTIVE: To characterize the prevalence of Mycoplasma bovis infection in
      backgrounding and stocker cattle operations and compare bacteriologic culture
      with PCR assay for detection of M bovis. DESIGN: Prospective descriptive study.
      ANIMALS: 432 calves, 3 to 9 months old, from 9 operations. PROCEDURES: 2 nasal
      swab specimens were collected from each calf. Swab specimens were evaluated via
      bacteriologic culture and PCR assay for organisms of the class Mollicutes and M
      bovis. Culture results were considered negative if no growth occurred within 21
      days. Positive results were indicated by characteristic colony formation with PCR
      assay confirmation. Deoxyribonucleic acid was extracted from 1 swab specimen for
      direct PCR assay for Mollicutes and M bovis. RESULTS: Of 432 calves, 374 (87%)
      had positive results for Mollicutes via PCR assay and 63 (15%) via culture. Seven
      (2%) calves had positive results for M bovis via PCR assay and 10 (2%) via
      culture. Prevalence of Mollicutes at the farm level ranged from 54% to 100% via
      PCR assay and from 0% to 59% via culture. Prevalence of M bovis at the farm level
      ranged from 0% to 4% via PCR assay and from 0% to 6% via culture. Calves that
      shed M bovis were significantly more likely to have a fever than were calves that
      did not shed M bovis. CONCLUSIONS AND CLINICAL RELEVANCE: M bovis was detected at
      a low level in recently purchased backgrounded and stocker calves in Georgia.
      Although slightly more infected calves were detected via culture and PCR assay
      together, PCR assay appeared to accurately identify M bovis at the farm level.

PMID- 17504047
TI  - Unusual history and initial clinical signs of Mycoplasma bovis mastitis and
      arthritis in first-lactation cows in a closed commercial dairy herd.
AB  - CASE DESCRIPTION: 9 first-lactation dairy cows in a closed dairy herd had
      swelling in the forelimbs and forelimb lameness. Mycoplasmal arthritis and
      mastitis were diagnosed. CLINICAL FINDINGS: Swelling of the carpal joint, diffuse
      subcutaneous edema from the carpal to metacarpophalangeal joints, and forelimb
      lameness were evident in 9 first-lactation cows 7 to 21 days after parturition.
      Diagnostic testing revealed that 3 of 3 bulk-tank milk samples, 3 milk samples
      from cows with clinical mastitis, 2 fluid samples obtained from arthritic joints,
      and samples from the lungs and spleen of a cow that had died yielded positive
      results for Mycoplasma spp. Nucleic acid sequence analysis performed by use of a
      PCR assay on the joint fluid and lung tissues confirmed infection with Mycoplasma
      bovis. TREATMENT AND OUTCOME: Affected cows were treated by IM administration of
      flunixin meglumine and dexamethasone for 3 days. All cows were nonresponsive to
      treatment (3 cows died, and the other 6 were culled). Follow-up culture for
      Mycoplasma spp of milk samples from the bulk tank and from all lactating cows was
      recommended to screen for chronic subclinical carriers. CLINICAL RELEVANCE:
      Mycoplasmal infections may cause unusual initial clinical signs or an atypical
      history. When dairy cattle, including those residing in closed herds, have
      lameness, swelling of the carpal or metacarpophalangeal joints, edema of the
      distal portions of the forelimbs, or polyarthritis, infection with Mycoplasma spp
      should be investigated. Delay in diagnosis of mycoplasmal infections in dairy
      herds can result in substantial financial loss and the establishment of chronic
      subclinical carriers.

PMID- 17504049
TI  - Infection with Mycobacterium simiae complex in four captive Micronesian
      kingfishers.
AB  - CASE DESCRIPTION: 4 captive adult Micronesian kingfishers (Halcyon cinnamomina
      cinnamomina) at 3 zoologic institutions were examined routinely or because of
      dyspnea or lethargy. CLINICAL FINDINGS: All birds had marked hepatomegaly. Two
      birds had dyspnea caused by compression of air sacs by the enlarged liver, and 1
      bird had generalized weakness and lethargy. Three birds had distended coelomic
      cavities, and 3 birds were thin or had lost weight. There were no consistent
      abnormalities in blood analytes. Results of most ancillary diagnostic tests such
      as acid-fast staining of cloacal or fecal swab specimens and culture of feces for
      acid-fast bacteria were negative. Results of examination of hepatic biopsy
      specimens in 2 of 4 birds were suggestive of mycobacteriosis. TREATMENT AND
      OUTCOME: 3 birds died or were euthanized soon after diagnosis. One kingfisher was
      isolated and monitored for 4 months without treatment and died during anesthesia
      for disease monitoring. Postmortem histologic examination revealed histiocytic
      hepatitis and acid-fast bacteria in all 4 birds. Bacteriologic culture of liver
      specimens yielded Mycobacterium simiae complex in all 4 birds. CLINICAL
      RELEVANCE: Infection with M simiae complex should be considered in ill
      Micronesian kingfishers, and further monitoring is warranted to determine whether
      this is an emerging pathogen in this species.

PMID- 17504059
TI  - Editorial: tissue engineering: a 20-year personal perspective.

PMID- 17504060
TI  - Satellite cells delivered by micro-patterned scaffolds: a new strategy for cell
      transplantation in muscle diseases.
AB  - Myoblast transplantation is a potentially useful therapeutic tool in muscle
      diseases, but the lack of an efficient delivery system has hampered its
      application. Here we have combined cell biology and polymer processing to create
      an appropriate microenvironment for in vivo transplantation of murine satellite
      cells (mSCs). Cells were prepared from single muscle fibers derived from C57BL/6
      Tgn enhanced green fluorescent protein (GFP) transgenic mice. mSCs were expanded
      and seeded within micro-patterned polyglycolic acid 3-dimensional scaffolds
      fabricated using soft lithography and thermal membrane lamination. Myogenicity
      was then evaluated in vitro using immunostaining, flow cytometry, and reverse
      transcription polymerase chain reaction analyses. Scaffolds containing mSCs were
      implanted in pre-damaged tibialis anterior muscles of GFP-negative syngenic mice.
      Cells detached from culture dishes were directly injected into contra-lateral
      limbs as controls. In both cases, delivered cells participated in muscle
      regeneration, although scaffold-implanted muscles showed a much higher number of
      GFP-positive fibers in CD57 mice. These findings suggest that implantation of
      cellularized scaffolds is better than direct injection for delivering myogenic
      cells into regenerating skeletal muscle.

PMID- 17504061
TI  - The effect of growth factor treatment on meniscal chondrocyte proliferation and
      differentiation on polyglycolic acid scaffolds.
AB  - The aim of this investigation was to determine the effect of growth factor
      treatment on ovine meniscal chondrocyte (OMC) proliferation in vitro and on the
      production of matrix proteins by OMCs grown within a polyglycolic acid (PGA)
      scaffold. Analysis of 72-h monolayer cultures using the mean transit time (MTT)
      assay revealed a greater increase in OMC numbers in the presence of platelet
      derived growth factor (PDGF)-AB, PDGF-BB, insulin-like growth factor (IGF)-I,
      transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor
      (bFGF) than in untreated controls. In contrast, IGF-II and bone morphogenetic
      protein-2 had no effect on OMC proliferation at the concentrations tested. The
      growth factors that elicited the greatest proliferative response (PDGF-AB, PDGF
      BB, TGF-beta1, and IGF-I) were subsequently tested for their ability to enhance
      OMC proliferation and differentiation within PGA scaffolds. Biochemical analysis
      revealed less glycosaminoglycan (GAG) production in the presence of all growth
      factors tested compared to untreated control samples. In contrast, all of the
      growth factors increased collagen type I production by OMCs within the scaffolds
      at day 20, and all except PDGF-BB resulted in an increase at day 39, when
      compared to appropriate control samples. With the exception of IGF-I, none of the
      growth factors tested had any significant effect on collagen type II production.
      Histological staining of sections from OMC-PGA scaffolds did not reveal any
      difference in GAG or collagen production between the treatment groups. However,
      immunohistochemical analysis demonstrated an increase in collagen type I
      expression and a decrease in collagen type II at day 39 in all growth
      factortreated constructs, concomitant with a high infiltration of cells. This
      suggests that PDGF-AB, PDGF-BB, TGF-beta1, and IGF-1 may be useful in future
      tissue engineering studies for promoting meniscal cell proliferation and
      differentiation within scaffolds.

PMID- 17504062
TI  - Skull bone regeneration in nonhuman primates by controlled release of bone
      morphogenetic protein-2 from a biodegradable hydrogel.
AB  - The objective of this study was to investigate the feasibility of biodegradable
      gelatin hydrogels as the controlled-release carrier of bone morphogenetic protein
      2 (BMP-2) to enhance bone regeneration at a skull defect of nonhuman primates.
      Hydrogels with 3 different water contents were prepared through glutaraldehyde
      crosslinking of gelatin with an isoelectric point of 9.0 under varied reaction
      conditions. A critical-sized defect (6 mm in diameter) was prepared at the skull
      bone of skeletally mature cynomolgus monkeys, and gelatin hydrogels incorporating
      various doses of BMP-2 were applied to the defects. When the bone regeneration
      was evaluated by soft radiography and bone mineral density (BMD) examinations,
      the gelatin hydrogel incorporating BMP-2 exhibited significantly higher
      osteoinduction activity than did an insoluble bone matrix that incorporated BMP-2
      (one of the best osteoinduction systems), although the activity depended on the
      water content of hydrogels. BMD enhancement was highest for the gelatin hydrogel
      that had a water content of 97.8 wt% among all types of hydrogels. Moreover, the
      gelatin hydrogel enabled BMP-2 to induce the bone regeneration in nonhuman
      primates even at low doses. We conclude that the controlled release of BMP-2 for
      a certain time period was essential to inducing the osteoinductive potential of
      BMP-2.

PMID- 17504063
TI  - Design of biphasic polymeric 3-dimensional fiber deposited scaffolds for
      cartilage tissue engineering applications.
AB  - This report describes a novel system to create rapid prototyped 3-dimensional
      (3D) fibrous scaffolds with a shell-core fiber architecture in which the core
      polymer supplies the mechanical properties and the shell polymer acts as a
      coating providing the desired physicochemical surface properties. Poly[(ethylene
      oxide) terephthalate-co-poly(butylene) terephthalate] (PEOT/PBT) 3D fiber
      deposited (3DF) scaffolds were fabricated and examined for articular cartilage
      tissue regeneration. The shell polymer contained a higher molecular weight of the
      initial poly(ethylene glycol) (PEG) segments used in the copolymerization and a
      higher weight percentage of the PEOT domains compared with the core polymer. The
      3DF scaffolds entirely produced with the shell or with the core polymers were
      also considered. After 3 weeks of culture, scaffolds were homogeneously filled
      with cartilage tissue, as assessed by scanning electron microscopy. Although
      comparable amounts of entrapped chondrocytes and of extracellular matrix
      formation were found for all analyzed scaffolds, chondrocytes maintained their
      rounded shape and aggregated during the culture period on shell-core 3DF
      scaffolds, suggesting a proper cell differentiation into articular cartilage.
      This finding was also observed in the 3DF scaffolds fabricated with the shell
      composition only. In contrast, cells spread and attached on scaffolds made simply
      with the core polymer, implying a lower degree of differentiation into articular
      cartilaginous tissue. Furthermore, the shell-core scaffolds displayed an improved
      dynamic stiffness as a result of a "prestress" action of the shell polymer on the
      core one. In addition, the dynamic stiffness of the constructs increased compared
      with the stiffness of the bare scaffolds before culture. These findings suggest
      that shell-core 3DF PEOT/PBT scaffolds with desired mechanical and surface
      properties are a promising solution for improved cartilage tissue engineering.

PMID- 17504064
TI  - Designing zonal organization into tissue-engineered cartilage.
AB  - Cartilage tissue engineering strategies generally result in homogeneous tissue
      structures with little resemblance to the native zonal organization of articular
      cartilage. The objective of this study was to use bilayered photopolymerized
      hydrogels to organize zone-specific chondrocytes in a stratified framework and
      study the effects of this three-dimensional coculture system on the properties of
      the engineered tissue. Superficial and deep zone chondrocytes from bovine
      articular cartilage were photoencapsulated in separate hydrogels as well as in
      adjacent layers of a bilayered hydrogel. Histology, mechanical testing, and
      biochemical analysis was performed after culturing in vitro. To evaluate the
      influence of coculture on tissue properties, the layers were separated and
      compared to constructs containing only superficial or deep cells. In the
      bilayered constructs, deep cells produced more collagen and proteoglycan than
      superficial cells, resulting in cartilage tissue with stratified, heterogeneous
      properties. Deep cells cocultured with superficial cells in the bilayered system
      demonstrated reduced proliferation and increased matrix synthesis compared to
      deep cells cultured alone. The bilayered constructs demonstrated greater shear
      and compressive strength than homogenous cell constructs. This study demonstrated
      that interactions between zone-specific chondrocytes affect the biological and
      mechanical properties of engineered cartilage. Strategies aimed to structurally
      organize zone-specific cells and encourage heterotypic cell interactions may
      contribute to improved functional properties of engineered cartilage.

PMID- 17504086
TI  - Copper (II) complexes with Ac-HXH-NHMe (X=Gly, Ala and Aib) peptide motifs:
      influence of increasing CH(3) groups at C(alpha) of residue X on the coordination
      in solution.
AB  - The interaction of Cu(II) ion with small peptides has been an interesting subject
      to clarify the role of copper in detail. As various Cu(II)-oligopeptide complexes
      can also be good models for the active centers of metalloenzymes, complexes of
      tripeptide and tetrapeptides are frequently investigated instead of the complexes
      of large peptides. The histidine side-chains of various metalloproteins
      frequently take part in the copper(II) coordination. Accordingly, we studied the
      coordination of Cu(II) to the N and C terminal protected tripeptide ligands L(A)
      (Ac-HisGlyHis-NHMe), L(B) (Ac-HisAlaHis-NHMe) and L(C) (Ac-HisAibHis-NHMe) in
      aqueous solution potentiometrially in order to determine the effect of C(alpha)
      methyl groups at middle residue acid on the ligation of the backbone NH and also
      on histidine's N(im) of coordination. Species distribution curves indicates that
      in acidic pH, all three peptides behave as bidentate ligands and a macrochelate
      forms on the metal coordination with the two histidine imidazolyl N. This
      coordination remains unaffected with the +I effect of increasing CH(3) groups at
      C(alpha) of middle residue. In the pH range 4-8, the tridentate coordination from
      the peptide is seen in ligand L(A) and L(B) while it is absent in L(C) due to +I
      effect of two C(alpha) methyl groups at middle residue as they makes N-terminal
      NH deprotonation difficult in this pH range and it takes place along with C
      terminal NH and only 4N coordinated species formed at higher pH. These 4N (N(im),
      N(-), N(-), N(im)) coordinated species are formed by all the three ligands at
      higher pH values.

PMID- 17504087
TI  - Proteomic analysis of jasmonic acid-regulated proteins in rice leaf blades.
AB  - Jasmonates play a critical role in plant defense against pathogens through
      regulation of the expression of defense-related genes. To study the role of
      jasmonic acid (JA) in the rice self-defense mechanism, a proteomic approach was
      applied. When 3-week-old rice cv. Java 14 was treated with 100 microM JA for 3
      days, numerous necrotic brown spots were observed on the leaf blade. Three-week
      old rice was treated with JA and proteins from cytosolic and membrane fractions
      of leaf blade were separated by two-dimensional polyacrylamide gel
      electrophoresis. A total of 305 proteins were detected in both cytosolic and
      membrane fractions. When rice plant was treated with 100 microM JA for 2 days, 12
      proteins were up-regulated and 2 proteins were down-regulated. Out of them, 8
      proteins were changed in dose dependence manner, while 4 proteins were changed in
      a time course manner. Among them, pathogenesis-related protein 5 (PR5) and
      probenazole inducible protein 1 (PBZ1) were significantly induced by 100 microM
      JA for 2 days. These results suggest that PR5 and PBZ1 are important proteins
      expressed down-stream of JA signals in rice cv. Java 14.

PMID- 17504088
TI  - Reevaluating the capability of Taq DNA polymerase: long PCR amplification.
AB  - We tested the ability of Taq DNA polymerase (Taq) to amplify long DNA fragments
      and showed that, if the conditions were set properly, Taq could successfully
      perform the "long PCR" up to 24 kb. The conditions include: (1) longer primers,
      (2) a 2-step cycling, and (3) a "long buffer." We propose that the most important
      requirements are the survival rate of Taq at high temperatures and that of the
      primers against the 5' to 3' exonuclease activity of Taq.

PMID- 17504089
TI  - The Blomia tropicalis allergens.
AB  - Blomia tropicalis allergens are the most important mite allergens in tropical
      regions. Most of them only have 30-40% sequence identity with their
      Dermatophagoides counterparts and they share low IgE cross reactivity and exhibit
      different immunobiology. Unlike the pyroglyphid counterparts, Blo t 5 is the
      major allergen whereas Blo t 1 only has modest allergenicity.

PMID- 17504090
TI  - Probing the effect of mutations on cytochrome C stability.
AB  - Although the tertiary structures of mitochondrial cytochromes c (cyts c) seem to
      be remarkably similar, there are variations in their amino acid sequences,
      stability and functional properties. GdnHCl-induced unfolding experiments on
      engineered yeast and horse cyt c were carried out with the aim to to clarify, at
      molecular level, some aspects concerning the stability of this class of proteins.
      The results obtained are discussed in the light of the three-dimensional
      structures of the two proteins.

PMID- 17504091
TI  - Functional characterization of Streptomyces coelicolor FtsY.
AB  - This study indicated that the N-terminus was dispensable for FtsY GTPase
      activity, and that the N-domain plays an essential role in the GTPase activity of
      the NG domain. In addition, the S.scoelicolor FtsY was able to restore function
      in an E. coli mutant. However, its NG domain was unable to play any roles.

PMID- 17504092
TI  - A short C-terminal region of alpha-synuclein protects a (R/S)-non-specific
      esterase from Archaeglobus fulgidus.
AB  - We show that alpha-synuclein could assist the molecular activity of a ketoprofen
      (R/S) nonspecific esterase from Archaeglobus Fulgidus. Specifically, several
      synthetic peptides from alpha-synuclein, each having random coil conformation in
      far-UV spectra, could protect the enzyme activity against stress conditions such
      as heat and organic solvents.

PMID- 17504093
TI  - Conformational analysis of Ac-NPGQ-NH(2) and Ac-VPaH-NH(2) by vibrational
      circular dichroism spectroscopy combined with molecular dynamics and quantum
      chemical calculations.
AB  - Conformational properties of two potentially beta-turn forming peptides were
      determined using a strategy which combines MD simulations, IR and VCD
      spectroscopy and quantum chemical calculations. This strategy could be a useful
      alternative for solution conformational analysis of short flexible peptides and
      could help to identify VCD features which are as yet unknown.

PMID- 17504094
TI  - The role of Bax/Bcl-2 and pro-caspase peptides in hypoxia/reperfusion-dependent
      regulation of MAPK(ERK): discordant proteomic effect of MAPK(p38).
AB  - BACKGROUND: The molecular regulation of MAPKs and apoptosis was investigated in a
      model of hypoxia-tolerance. Survival of neurons in Chrysemys picta bellii, an
      anoxia-tolerant turtle, involves a reduction in energy metabolism. The
      biochemical/physiological mechanisms of anoxia tolerance have been examined at
      the level of ion transport and ATP turnover. However, changes in the
      phosphorylation state of key enzymes and kinases, mainly, MAPKs, may occur during
      anoxia, thereby reversible protein phosphorylation could be a critical factor and
      major mechanism of metabolic reorganization for enduring anaerobiosis. METHODS:
      If a turtle were to undergo hypoxia akin to that experienced in its native
      habitat, it was placed in a glass aquarium filled with water to within a half
      inch of the top. After the turtle was anesthetized, through extended hypoxia or
      anesthesia, the animal was sacrificed by decapitation. The brain was then excised
      and placed in anoxic artificial cerebrospinal fluid. Total protein extraction was
      performed by homogenizing brain in a buffer, followed by threonine and tyrosine
      phosphorylation determination of MAPKs, and caspase activity. RESULTS: MAPK(p38)
      was decreased after reoxygenation following 1 day and 1 week hypoxia. The effect
      of hypoxia on the phosphorylation of MAPK(ERK) was biphasic: Enhancement at 5h
      and inhibition at 6 weeks. Pro-caspases 8/9 were unchanged by hypoxia until
      increasing at 6 weeks. Both pro-caspases were upregulated by reoxygenation at 1
      day or 6 weeks hypoxia. Neither hypoxia nor reoxygenation induced the cleavage of
      pro-caspases 8/9 into p20 and p10, respectively. Furthermore, hypoxia induced Bax
      at 3 days and 1 week, and reoxygenation increased Bax #8776; 4-fold at 1 day.
      Although the expression of Bcl-2 was slightly increased by hypoxia, [Bcl-2] was 3
      4-fold smaller in comparison with Bax. CONCLUSION: These results indicate that
      hypoxia up-regulates MAPK(ERK) but not MAPK(p38;) hypoxia/reperfusion increases
      the expression of caspases and pro-apoptotic cofactors. The patterns of MAPK
      regulation suggest the significance of these kinases in cellular adaptation to
      oxygen deprivation with biomedical correlations, and thereby identify novel
      natural responsive signaling cofactors in Chrysemys picta bellii with potential
      pharmacologic and clinical applications.

PMID- 17504095
TI  - Discordant tissue-specific expression of SAPK/MAPK(JNK)-related cofactors in
      hypoxia and hypoxia/reoxygenation in a model of anoxia-tolerance.
AB  - BACKGROUND: Pursuant to establishing the proteomic distribution of
      MAPK(ERK)/MAPK(p38) in the brain in a model of hypoxia-tolerance [Haddad, Protein
      Pept Lett, In press, 2007], I therein exclusively report the differential
      expression of MAPK(JNK) and related upstream and downstream kinases in various
      organs of the anoxia-tolerant turtle. Despite the fact that the aforementioned
      mechanisms involved dual expression of MAPK(ERK), the mechanistic distribution of
      MAPK(JNK) has not been previously unraveled. Changes in the phosphorylation state
      of MAPKs may occur during anoxia, thereby reversible protein phosphorylation
      could be a critical factor and major mechanism of metabolic reorganization for
      enduring anaerobiosis. METHODS: If a turtle were to undergo hypoxia akin to that
      experienced in its native habitat, it was placed in a glass aquarium filled with
      water to within a half inch of the top. After the turtle was anesthetized,
      through extended hypoxia or anesthesia, the animal was sacrificed by
      decapitation. The brain and other organs were then excised and placed in anoxic
      artificial cerebrospinal fluid. Total protein extraction was performed by
      homogenizing various organs in a suitable buffer, followed by determination of
      the phosphorylation states of SEK-1/MKK-4, SAPK/MAPK(JNK) and c-Jun activating
      protein (AP)-1. RESULTS: SEK-1/MKK-4 expression was mild in the cortex as
      compared with the manifold hypoxic (2h) induction in the liver. Continuous
      imposition of hypoxia (1 day - 1 week) increased the expression of SEK-1/MKK-4,
      thereafter declined at 3 weeks hypoxia. Hypoxia/reoxygenation weakly induced SEK
      1/MKK-4 expression in cortex, in contrast with a strong induction in the liver,
      but not in other organs. Hypoxia (2h - 3 weeks) did not induce SAPK/MAPK(JNK)
      expression in cortex, despite prominent increase in liver, with mild
      reoxygenation effect. The normoxic induction of c-Jun AP-1 in cortex and rest of
      brain (ROB) was reduced with imposition of hypoxia (2h - 1 week). Furthermore,
      hypoxia (2h - 3 weeks) upregulated expression of c-Jun AP-1 in liver, heart and
      spleen, an effect abrogated with hypoxia/reoxygenation. CONCLUSION: These results
      indicate that hypoxia differentially up-regulates the expression of MAPK(JNK)
      related cofactors with organ-specific distribution. Since these modules are
      involved with neuroprotection in Chrysemys picta bellii, the expression of MAPKs
      bears relative mechanisms of specific responses to hypoxia tolerance.

PMID- 17504096
TI  - Molecular simulations of rhodopsin tetrameter.
AB  - Di/oligomerization of G-protein coupled receptors (GPCRs) is well established,
      however very little is known regarding the interaction details. Current paper
      presents results of molecular dynamics simulations of theoretical model of
      rhodopsin tetramer with transducine (Gt) in lipid bilayer. Ligand-protein and
      receptor-receptor interactions have been proposed.

PMID- 17504097
TI  - New hope for the diagnosis and therapy of Alzheimer's disease.
AB  - Improperly folded metal cofactor-containing proteins (e.g., copper chaperone for
      superoxide dismutase, CCS) are believed to play a key role in several protein
      misfolding diseases (e.g., Alzheimer's disease or Amyotrophic Lateral Sclerosis)
      because under regular physiological conditions, metallochaperones activate or
      stabilize the native conformation of important metalloproteins (e.g., superoxide
      dismutase) in certain cellular processes. For an improved diagnosis and therapy
      of neurodegenerative diseases, new methodologies have to be developed that enable
      a well-defined differentiation between properly folded and inactive
      metalloproteins in clinical samples. In the literature it is reported that
      different high molecular mass metal-containing proteins were isolated in brain
      samples from Alzheimer's patients and in vegetables by using a 2-dimensional
      polyacrylamide gel electrophoresis (2-DE) procedure. In the present article,
      selected results of these studies are scrutinized and compared with some results
      obtained by a standardized method termed 'quantitative preparative native
      continuous polyacrylamide gel electrophoresis (QPNC-PAGE)'. Conclusively, QPNC
      PAGE is a highly efficient approach used by biochemists to resolve native and
      denatured metalloproteins (MW 6 - > or = 200 kDa) in complex protein mixtures.

PMID- 17504098
TI  - Characterization of a novel ADPase in Bothrops jararaca snake venom involved in
      nucleotide hydrolysis.
AB  - Snake venoms hydrolyze several phosphorylated substrates. However, not is clearly
      understood which enzyme(s) is (are) involved in these process. Here, we propose
      the existence of an independent ADPase activity. In addition, we studied the
      reactions mechanism of nucleotide hydrolysis. This system resembles membrane ecto
      nucleotidases and acts with a multi enzymatic complex transforming ATP in
      adenosine without the accumulation of intermediates.

PMID- 17504099
TI  - Crystallization and preliminary crystallographic study of DNA polymerase from
      Pyrococcus furiosus.
AB  - A new member of archaeal DNA polymerase from Pyrococcus furiosus was
      crystallized. Diffraction data to 3.1 A of the selenomethionine-derivatized
      crystal were collected, and preliminary crystallographic study has been
      completed. The crystal belongs to the space group C2 with unit cell parameters of
      a = 93.2 A, b = 124.9 A, c = 87.7 A, alpha = 90 degrees , beta = 109.7 degrees ,
      and gamma = 90 degrees . Assuming the presence of one molecule in the asymmetric
      unit, the solvent content of the crystal is estimated to be 54%, corresponding to
      a Matthews coefficient V(M) of 2.7A (3) Da(-1).

PMID- 17504100
TI  - Crystallization and preliminary X-ray diffraction analysis of PD-L1, a highly
      glycosylated ribosome inactivating protein with DNase activity.
AB  - PD-L1 is a highly glycosylated type 1 ribosome inactivating protein, from
      Phytolacca dioica leaves, with the peculiarity to act also as a DNase. PD-L1 has
      been successfully crystallized using vapour diffusion and seeding techniques.
      Crystals belong to the monoclinic C2 space group, with unit cell dimensions
      a=161.01, b=34.73, c=120.63 A, beta=127.99 degrees . Two molecules are present in
      the asymmetric unit. Phase determination has been achieved using molecular
      replacement.

PMID- 17504102
TI  - Structure of glutamate receptors.
AB  - Glutamate receptors mediate a vast array of processes in plants, animals and
      bacteria. In particular, the ionotropic glutamate receptors (iGluRs) are the most
      abundant excitatory neurotransmitter receptors in the mammalian central nervous
      system. Because these proteins are constructed from distinct folding domains,
      most of which can be traced to bacterial precursors, the analyses of these
      important receptor proteins has been performed on a variety of levels ranging
      from atomic structure and dynamics to behavioral studies. This review will focus
      on the structure and dynamics of iGluRs, with particular emphasis on the role
      that the glutamate-binding domain (S1S2) plays in receptor function.

PMID- 17504103
TI  - Pharmacology of ampakine modulators: from AMPA receptors to synapses and
      behavior.
AB  - Ampakines are drugs structurally derived from aniracetam that potentiate currents
      mediated by AMPA type glutamate receptors. These drugs slow deactivation and
      attenuate desensitization of AMPA receptor currents, increase synaptic responses
      and enhance long-term potentiation. This review focuses mainly on recent
      physiological studies and on evidence for two distinct subfamilies. Type I
      compounds like CX546 are very effective in prolonging synaptic responses while
      type II compounds like CX516 mainly increase response amplitude. Type I and II
      drugs do not compete in binding assays and thus presumably act through separate
      sites. Their differences are likely to have consequences also for synaptic
      plasticity and behavior. Thus, while all ampakines facilitated long-term
      potentiation, only CX546 enhanced long-term depression. Further discussed are
      studies showing that ampakine effects vary substantially between neurons, with
      increases in EPSCs being larger in CA1 pyramidal cells than in thalamus and in
      hippocampal interneurons. In behavioral tests, ampakines facilitate learning in
      many paradigms including odor discrimination, spatial mazes, and conditioning,
      and they improved short-term memory in a non-matching-to-sample task. Positive
      results were also obtained in various psychological tests with human subjects.
      The drugs were effective in correcting behaviors in various animal models of
      schizophrenia and depression. Lastly, evidence is discussed that ampakines have
      few adverse effects at therapeutically relevant concentrations and that they
      protect neurons against neurotoxic insults, in part by mobilizing growth factors
      like BDNF. Type II drugs like CX516 in particular appear to be inherently safe
      since their ability to prolong responses is kinetically limited.

PMID- 17504104
TI  - AMPA receptor potentiators: application for depression and Parkinson's disease.
AB  - Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors
      mediate most of the excitatory neurotransmission and play a key role in synaptic
      plasticity in the mammalian central nervous system (CNS). In recent years several
      classes of AMPA receptor potentiators have been reported in the literature,
      including pyrrolidones (piracetam, aniracetam), benzothiazides (cyclothiazide),
      benzylpiperidines (CX-516, CX-546) and biarylpropylsulfonamides (LY392098,
      LY404187, LY450108, LY451395 and LY503430). Clinical and preclinical data have
      suggested that positive modulation of AMPA receptors may be therapeutically
      effective in the treatment of cognitive deficits. However, recent evidence has
      shown that in addition to modulating fast synaptic plasticity and memory
      processes, AMPA receptor potentiators alter downstream signalling pathways and
      may thereby have utility in other CNS disorders. The present review summarises
      studies into the effects of AMPA receptor potentiators (with a focus on the
      biarylpropylsulfonamides) in rodent models of depression and Parkinson's disease.

PMID- 17504105
TI  - Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA
      receptor block by memantine and S-nitrosylation.
AB  - Alzheimer's disease (AD) and Vascular dementia represent the most common forms of
      dementia. If left unabated, the economic cost of caring for patients with these
      maladies would consume the entire gross national product of the industrialized
      world by the middle of this century. Until recently, the only available drugs for
      this condition were cholinergic treatments, which symptomatically enhance
      cognitive state to some degree, but they were not neuroprotective. Many potential
      neuroprotective drugs tested in clinical trials failed because of intolerable
      side effects. However, after our discovery of its clinically-tolerated mechanism
      of action, one putatively neuroprotective drug, memantine, was recently approved
      by the European Union and the U.S. Food and Drug Administration (FDA) for the
      treatment of dementia. Recent phase 3 clinical trials have shown that memantine
      is effective in the treatment of both mild and moderate-to-severe Alzheimer's
      disease and possibly Vascular dementia (multi-infarct dementia). Here we review
      the molecular mechanism of memantine's action and also the basis for the drug's
      use in these neurological diseases, which are mediated at least in part by
      excitotoxicity. Excitotoxicity is defined as excessive exposure to the
      neurotransmitter glutamate or overstimulation of its membrane receptors, leading
      to neuronal injury or death. Excitotoxic neuronal cell damage is mediated in part
      by overactivation of N-methyl-D-aspartate (NMDA)-type glutamate receptors, which
      results in excessive Ca(2+) influx through the receptor associated ion channel
      and subsequent free radical formation. Physiological NMDA receptor activity,
      however, is also essential for normal neuronal function. This means that
      potential neuroprotective agents that block virtually all NMDA receptor activity
      will very likely have unacceptable clinical side effects. For this reason many
      previous NMDA receptor antagonists have disappointingly failed advanced clinical
      trials for a number of neurodegenerative disorders. In contrast, studies in our
      laboratory have shown that the adamantane derivative, memantine, preferentially
      blocks excessive NMDA receptor activity without disrupting normal activity.
      Memantine does this through its action as an uncompetitive, low-affinity, open
      channel blocker; it enters the receptor-associated ion channel preferentially
      when it is excessively open, and, most importantly, its off-rate is relatively
      fast so that it does not substantially accumulate in the channel to interfere
      with subsequent normal synaptic transmission. Clinical use has corroborated the
      prediction that memantine is well tolerated. Besides Alzheimer's disease,
      memantine is currently in trials for additional neurological disorders, including
      HIV-associated dementia, depression, glaucoma, and severe neuropathic pain. A
      series of second-generation memantine derivatives are currently in development
      and may prove to have even greater neuroprotective properties than memantine.
      These second-generation drugs take advantage of the fact that the NMDA receptor
      has other modulatory sites in addition to its ion channel that potentially could
      also be used for safe but effective clinical intervention.

PMID- 17504106
TI  - The molecular basis of conantokin antagonism of NMDA receptor function.
AB  - The N-methyl-D-aspartate receptor (NMDAR), a subtype of ionotropic glutamate
      receptor, has been implicated in a host of chronic and acute neurological
      disorders. Accordingly, much emphasis has been placed on the development of safe
      and effective therapeutic agents that specifically antagonize this target. The
      conantokins are a class of small, naturally occurring peptides that inhibit ion
      flow through the NMDAR. Some conantokins demonstrate receptor subunit
      selectivity, a pharmacological attribute of emerging importance in the search for
      suitable drug candidates. The current review summarizes the NMDAR inhibitory
      properties of the conantokins, including structure-function relationships and
      mechanism of action. This information is fundamental to the rational design of
      suitable agents that can effectively treat pathophysiologies linked to NMDAR
      dysfunction.

PMID- 17504107
TI  - Glycine transporter 1 inhibitors and modulation of NMDA receptor-mediated
      excitatory neurotransmission.
AB  - In the central nervous system, glutamate is essential for a proper synaptic
      communication in neuronal networks supporting critical behavioral activities such
      as learning and memory. Dysfunction of glutamatergic excitatory neurotransmission
      has been implicated in numerous neurological and pyschiatric disorders and a
      growing body of research suggests that potentiation of NMDA receptor function may
      represent a novel approach for the treatment of schizophrenia. An actively
      pursued strategy to potentiate NMDA receptor function is to increase synaptic
      levels of the neurotransmitter glycine by blocking the glycine transporter type 1
      (GlyT1). Since glycine acts as a co-agonist at the NMDA receptor, this approach
      could enhance the effectiveness of normal NMDA receptor-mediated glutamatergic
      neurotransmission. Recent research on the physiology of this uptake system as
      well as on the development and preclinical testing of novel GlyT1 inhibitors have
      greatly enhanced our knowledge of the role of this transporter in the modulation
      of NMDA receptor activity and suggested that this approach may be feasible.
      Clinical studies with novel glycine reuptake inhibitors will provide critical
      information regarding the validity of this therapeutic concept for the treatment
      of schizophrenia and other disorders associated with NMDA receptor hypofunction.

PMID- 17504108
TI  - Metabotropic glutamate receptors as drug targets.
AB  - L-glutamate (Glu), the main excitatory amino acid neurotransmitter in the
      mammalian central nervous system, is involved in many physiological functions,
      including learning and memory, but also in toxic phenomena occurring in numerous
      degenerative or neurological diseases. These functions mainly result from its
      interaction with Glu receptors (GluRs). The broad spectrum of roles played by
      glutamate derived from the large number of membrane receptors, which are
      currently classified in two main categories, ionotropic (iGluRs) and metabotropic
      (mGluRs) receptors. The iGluRs are ion channels, permeant to Na(+) (Ca(2+)) while
      the mGluRs belongs to the superfamily of G-protein coupled receptors (GPCRs).
      Despite continuous efforts over more than two decades, the use of iGluR agonists
      or antagonists to improve or inhibit excitatory transmission in pathological
      states still remains a major challenge, though the discovery and development of
      recent molecules may prove it worthwhile. This probably results form the vital
      role of fast excitatory transmission in many fundamental physiological functions.
      Since the discovery of mGluRs, hope has emerged. Indeed, mGluRs are mainly
      involved in the regulation of fast excitatory transmission. Consequently, it was
      logically thought that modulating mGluRs with agonists or antagonists might lead
      to more subtle regulation of fast excitatory transmission than by directly
      blocking iGluRs. As a result of intensive investigation, new drugs permitting to
      discriminate between these receptors have emerged. Moreover, a new class of
      molecules acting as negative or positive allosteric modulators or mGluRs is now
      available and appears to be promising. In the following, we will review the
      classification of mGluRs and the functions in which mGluRs are involved. We will
      focus on their potential as therapeutic targets for improving numerous
      physiological functions and for different neurodegenerative and neuropsychiatric
      disorders, which are related to malfunction of Glu signaling in human beings.

PMID- 17504110
TI  - Growth regulation in the mycobacterial cell.
AB  - A framework was developed to provide an integrated view of mycobacterial growth
      and its regulation. The topics reviewed include the properties of cell cultures
      and their relation to properties of individual cells, cell sizes and
      macromolecular compositions, uptake of nutrients through the cell envelope,
      protein biosynthesis, core metabolic pathways, generation of an electrochemical
      gradient of protons, ATP synthesis and the control of energy generation.

PMID- 17504111
TI  - Regulation of cell wall synthesis and growth.
AB  - The replication and growth of Mycobacterium tuberculosis are fundamentally linked
      to the synthesis and extension of its complex cell wall. Incorporation of new
      wall material must be tightly regulated so that its deposition does not
      compromise the extant structure. M. tuberculosis also produces an impressive
      array of complex bioactive lipids that are intimately involved in pathogenesis
      and protective immunity. The profiles of these lipids are regulated appropriately
      to allow the bacterium to respond to the prevailing conditions it faces in vivo.
      A number of regulatory strategies employed by M. tuberculosis to control cell
      wall biosynthesis and cell division have now been elucidated. The review
      highlights the role of alternative sigma factors with extracytoplasmic function
      in the activation of genes for biosynthesis of complex lipids involved in
      pathogenicity. Rel(Mtb) and CRP(Mt) play roles in cell wall responses to general
      nutrient deprivation by synthesis and sensing of starvation second messengers,
      respectively. Recently, the importance of protein phosphorylation networks in
      cell wall biosynthesis has attracted considerable interest. A plethora of two
      component and eukaryotic-like serine/threonine protein kinases systems have been
      discovered and several are implicated in cell-division, morphogenesis and
      regulation of the profile of complex bioactive lipids elaborated by the pathogen.

PMID- 17504112
TI  - Transcriptional responses of Mycobacterium tuberculosis exposed to adverse
      conditions in vitro.
AB  - Mycobacterium tuberculosis encounters a range of stimuli in the host.
      Understanding the environmental cues that initiate the transcriptional response
      of M. tuberculosis, which enable the bacterium to replicate and/or survive in the
      host, will provide markers that are specific to different stages of disease,
      further refining the search for improved treatments and vaccines. Studying M.
      tuberculosis gene expression in vivo is technically challenging and more amenable
      in vitro experiments are being used to aid interpretation and to dissect the
      signals that are responsible for controlling subsets of genes. Key parameters
      that affect the growth of a pathogen in the host include nutrient status,
      environmental pH, oxygen availability, and host defences. Studying gene
      expression, pathogenicity, and physiology of M. tuberculosis that has been
      exposed to these relevant host conditions in vitro will further increase our
      understanding of the virulence factors that M. tuberculosis requires to establish
      disease. Complementary information obtained by metabolic flux analysis,
      proteomics, and regulatory networks analysis will enable a clearer picture of how
      transcriptional responses translate to changes in the metabolome and physiology
      of the organism.

PMID- 17504114
TI  - Current strategies for identifying and validating targets for new treatment
      shortening drugs for TB.
AB  - There is an urgent need for new drugs to treat tuberculosis. During the last
      forty years the only drugs to have been developed are variations on existing
      ones, but new drug candidates must offer improvements over existing agents. In
      particular, we require new drugs having novel mechanisms of action that are
      active against drug-resistant strains and also kill persistent bacilli, thus
      shortening the length of chemotherapy. Recent advances in our understanding of
      the biology of Mycobacterium tuberculosis, in particularly the availability of
      the genome sequence coupled with development of new genetic tools, have greatly
      contributed to the discovery of potential drug targets for new antituberculars.
      However, although many potential new drug targets have been identified, greater
      effort is required in target validation to show properly that they are essential
      for bacterial growth and survival. In this review, the current drug development
      pipeline and the strategies employed to identify and validate novel tuberculosis
      drug targets are presented.

PMID- 17504113
TI  - Microarray analysis of whole genome expression of intracellular Mycobacterium
      tuberculosis.
AB  - Analysis of the changing mRNA expression profile of Mycobacterium tuberculosis
      though the course of infection promises to advance our understanding of how
      mycobacteria are able to survive the host immune response. The difficulties of
      sample extraction from distinct mycobacterial populations, and of measuring mRNA
      expression profiles of multiple genes has limited the impact of gene expression
      studies on our interpretation of this dynamic infection process. The development
      of whole genome microarray technology together with advances in sample collection
      have allowed the expression pattern of the whole M. tuberculosis genome to be
      compared across a number of different in vitro conditions, murine and human
      tissue culture models and in vivo infection samples. This review attempts to
      produce a summative model of the M. tuberculosis response to infection derived
      from or reflected in these gene expression datasets. The mycobacterial response
      to the intracellular environment is characterised by the utilisation of lipids as
      a carbon source and the switch from aerobic/microaerophilic to anaerobic
      respiratory pathways. Other genes induced in the macrophage phagosome include
      those likely to be involved in the maintenance of the cell wall and genes related
      to DNA damage, heat shock, iron sequestration and nutrient limitation. The
      comparison of transcriptional data from in vitro models of infection with complex
      in vivo samples, together with the use of bacterial RNA amplification strategies
      to sample defined populations of bacilli, should allow us to make conclusions
      about M. tuberculosis physiology and host microenvironments during natural
      infection.

PMID- 17504115
TI  - Molecular tools for typing and branding the tubercle bacillus.
AB  - During the past two decades, a number of variable genetic sequences have been
      uncovered that permit molecular typing of Mycobacterium tuberculosis complex
      (MTC) organisms. Since the determination of the M. tuberculosis, and later M.
      bovis, genome sequences, the nature of these variable genetic sequences has
      become more evident, permitting a clearer recognition of which molecular tools
      lend themselves best to certain applications. In this review, 'classical'
      genotyping methods for molecular epidemiologic uses are briefly discussed,
      followed by a more detailed description of post-genomic typing methods, including
      large sequence polymorphisms otherwise referred to as genomic deletions. Because
      genomic deletions represent unique event polymorphisms not prone to reversion,
      these mutations effectively 'brand' bacterial lineages, including species/sub
      species of the MTC and specific clades of M. tuberculosis sensu stricto. Genomic
      deletions therefore provide a new opportunity to accurately classify organisms
      for diagnostic and epidemiologic purposes, serving as the basis for further study
      of the natural variability across MTC organisms.

PMID- 17504116
TI  - Correlates of immune protection from tuberculosis.
AB  - Due to the failure of chemotherapy and the only available vaccine, BCG, to
      control tuberculosis (TB) disease, there is an urgent need to develop new
      vaccines and therapeutics. The identification of correlates of immune protection
      or "biomarkers" will facilitate the rational design of vaccines and drugs for the
      prevention and clearance of TB infection. Although it is known that IFN-gamma is
      essential for protective immunity, animal and human studies have found that IFN
      gamma alone is not sufficient for the prevention of TB disease. There is evidence
      that IL-23, a recently described member of the IL-12 family of cytokines, is
      important in the immuno-pathogenesis of TB. There is also evidence that
      regulatory T cells (Treg) are present in TB disease and that Treg may suppress
      effector T cell responses. In the last five years, clinical studies have been
      able to use Mycobacterium tuberculosis specific antigens, such as ESAT-6, to
      focus on recently infected, healthy contacts of TB patients in endemic countries.
      Advances in techniques such as multi-parameter flow cytometry and DNA microarray
      analysis will enable us to study these cohorts in great detail and facilitate the
      identification of immune correlates for the rational design of drugs and vaccines
      for the treatment and prevention of TB.

PMID- 17504117
TI  - Th2 cytokines in susceptibility to tuberculosis.
AB  - We need to understand what is different about susceptibility to tuberculosis (TB)
      in developing countries where most TB occurs, and where the current vaccine,
      Bacillus Calmette et Guerin (BCG) usually fails to protect. The presence of a
      background mixed IFN-gamma and Th2 response to mycobacterial antigens before
      infection with M. tuberculosis (Mtb), and the development of a large IL-4
      response during progressive TB, are characteristics of individuals in the
      locations where BCG fails, which are also seen in animal models in the same
      countries. Recent data suggest that the background Th1 component in developing
      countries protects from low dose challenge with Mtb in mouse and man, but that
      following high dose challenge the pre-existing IL-4 component increases and
      blocks immunity unless the individual's immune system releases IL-4delta2, an
      antagonist of IL-4, which is raised in the blood of donors with stable latent TB.
      We outline how IL-4 (and IL-13) can undermine Th1-mediated immunity and drive
      inappropriate alternative activation of macrophages. The mechanisms of the
      effects of IL-4 include impaired antimicrobial activity due to reduced TNF-alpha
      mediated apoptosis of infected cells, reduced activity of iNOS, increased
      availability of iron to intracellular Mtb, and increased proliferation of antigen
      specific FOXP-3+ regulatory T cells. IL-4 also increases the toxicity of TNF
      alpha and drives pulmonary fibrosis, thus enhancing immunopathology. The
      conclusion is that a vaccine that will work in developing countries might need to
      do more than enhance the existing Th1 response. In these environments it might be
      more important to block the Th2 component.

PMID- 17504118
TI  - Glycogen synthase kinase-3 beta; a new target in pancreatic cancer?
AB  - Glycogen synthase kinase (GSK) was initially described as a key enzyme involved
      in glycogen metabolism. However, since that time it has been found to regulate a
      diverse range of cell functions. In addition to having a major role in the
      regulation of the important onco-protein beta-catenin, GSK is also a critical
      regulator of NF-kappaB. NF-kappaB comprises a family of transcription factors
      which activate the expression of a wide array of genes involved in inflammation,
      tumourigenesis, metastasis, differentiation, embryonic development, apoptosis.
      Inflammation mediated by the NF-kappaB family has been implicated in the
      initiation of pancreatic cancer, resistance to chemotherapy and the development
      of the debilitating cancer cachexia seen with advanced disease. Hence, GSK has
      potential as an important new target both in the treatment of resectable
      pancreatic cancer as an adjuvant to surgery, and in the palliation of inoperable
      tumours.

PMID- 17504119
TI  - Metastasis-associated protein S100A4: spotlight on its role in cell migration.
AB  - S100A4 (also known as Mts1, metastasin, p9Ka, pEL98, CAPL, calvasculin, Fsp-1,
      placental calcium-binding protein) belongs to the family of EF-hand calcium
      binding proteins, whose expression is elevated in a number of pathological
      conditions. Although it is well documented that S100A4 is expressed in cancer
      cells and contributes to tumor cell motility and metastatic progression, the
      exact underlying mechanisms remain elusive. An important characteristic feature
      of S100 proteins is their dual function, inside and outside the cell. In this
      review, we focus on the intracellular function of S100A4. The review contains
      structural analysis of S1004 in comparison with other members of S100 proteins.
      Possible modes of the interaction of S100 proteins with targets are described.
      Several examples of best-studied molecular interactions involving S100A4 with
      heavy chain of nonmuscle myosin IIA, LAR-interacting protein liprin beta1 and
      tumor suppressor protein p53 are provided. We suggest that the binding of S100A4
      to these molecules is critical for the S100A4 function. Further studies of the
      implications of these interactions in different molecular pathways may shed
      additional light on the role of S100A4 protein in the control of tumor cell
      motility and migration. We discuss the approaches for down-regulation of S100A4
      expression and their potential for application in the clinics.

PMID- 17504121
TI  - Non-homologous DNA end joining in anticancer therapy.
AB  - Non-homologous DNA end joining (NHEJ) is the major pathway for the repair of
      double-strand breaks (DSBs) in human cells. Proteins involved in NHEJ pathway can
      become molecular targets in the treatment of cancer. Inhibition of this pathway
      leads to radio- and chemosensitization of cancer cells. This review will focus on
      the new therapeutic strategies for NHEJ pathway inhibition and their application
      in anticancer therapy.

PMID- 17504120
TI  - Cancer vaccines for hormone/growth factor immune deprivation: a feasible approach
      for cancer treatment.
AB  - One of the older and most validated cancer treatments is endocrine therapy. Some
      tumors are dependent on hormone stimulation for growth, and therefore therapeutic
      interventions aiming to deprive the cells of the hormone are feasible and have
      been successful. Tumor growth also depends in some cases on growth factors, so
      that the concept of hormone-dependence can be extended to growth factors
      deprivation. Hormone deprivation has been therapeutically achieved up to now by
      surgical, radiation and chemical means. However, the immune system usually can be
      manipulated to recognize hormones and growth factors, and in fact some autoimmune
      diseases exists involving autoantibodies against hormones. The idea of inducing a
      deprivation of hormones and growth factors by active immunizations is appealing,
      and initial evidence about the feasibility of this approach is starting to appear
      in the literature. Clinical trials have been initiated using immunization with
      human chorionic gonadotrophin (hCG), gastrin, luteinizing hormone releasing
      hormone (LHRH) / gonadotropin releasing hormone (GnRH) and epidermal growth
      factor (EGF). Preliminary data already show that antibody titers can be elicited,
      which results in a decrease in the concentration of a given hormone or growth
      factor. Both the antibody titers and the decrease in the hormone level are
      related to survival. This immunological approach for hormone and growth factor
      deprivation creates the possibility of chronic management of advanced cancer
      patients.

PMID- 17504122
TI  - The kinase inhibitor imatinib--an immunosuppressive drug?
AB  - The phenylaminopyrimidine-derivate Imatinib mesylate has been developed for
      targeted inhibition of the Abelson kinase (c-ABL), which is constitutively
      activated when translocated to the genetic locus of the breakpoint cluster region
      (leading to the BCR/ABL fusion gene), thereby forming the causative pathogenetic
      event for the development of chronic myeloid leukemia (CML). Of note, due to its
      physico-chemical properties, kinase specificity of Imatinib is limited. Despite
      of its well documented clinical efficacy mediated by inhibition of constitutively
      activated tyrosine kinases such as BCR/ABL in CML, PDGF-RA in HES and mutated c
      kit in GIST patients, other tyrosine kinases such as Flt-3, Lck and mitogen
      activated kinases (MAPK) are affected as well. Accordingly, it has recently been
      shown that therapeutic doses of Imatinib also target a variety of immune cells,
      e.g. by modulating the differentiation of dendritic cells (DC) as well as by
      impeding proper T-cell and macrophage function. In contrast, combining Imatinib
      with Interleukin 2 (IL-2) potently activates NK-cells and led to the description
      of a new subclass of DC, so-called IK-DC. The latter mediate Imatinib/IL-2
      induced regression of tumors in pre-clinical animal models via production of high
      amounts of IFN-gamma and the death receptor ligand TRAIL. Thus, Imatinib exerts
      potent immuno-modulatory effects in vitro and in vivo, which will be discussed
      together with their clinical relevance in detail throughout this review.

PMID- 17504123
TI  - MUC1 is a promising therapeutic target for prostate cancer therapy.
AB  - Prostate cancer (CaP) is one of the most common malignancies in men, and the
      incidence of CaP is increasing. Because of the limitations of current therapeutic
      approaches, many patients die of secondary disease (metastases). Mucins are used
      as diagnostic markers as well as therapeutic targets due to their aberrant and
      unique expression pattern during cancer progression. There is a growing interest
      in mucins as treatment targets in human malignancies, including CaP. So far, 21
      mucin genes have been identified. Of these, MUC1 has been investigated most
      extensively. In neoplastic tissues, MUC1 is underglycosylated compared with that
      in normal tissues. The reduced glycosylation permits the immune system to access
      the peptide core of the tumor-associated underglycosylated MUC1 antigen (uMUC1)
      and reveal epitopes that are masked in the normal cell. This feature makes it
      possible to design an antibody that discriminates between normal and
      adenocarcinoma cells and target tumor-associated MUC1 with toxins or
      radionuclides, or use a vaccine targeting tumor-associated MUC1 antigen. The
      results from our recent study have shown that over-expression of MUC1 plays a
      very important role in CaP progression and MUC1 is an ideal target for targeted
      therapy to control micrometastases and hormone refractory disease. This review
      will cover our current understanding of the structure and functions of MUC1,
      summarize its expression on human CaP tissues and focus on the MUC1-based
      immunotherapy for control of metastatic CaP.

PMID- 17504124
TI  - Current status and future of target-based therapeutics.
AB  - With the beginning of the 21st century, a new and exciting era for cancer therapy
      has begun with the appearance of molecular targeted drugs. Numerous drugs for
      chemotherapy have been discovered following careful screening of natural and
      synthetic components. After screening, candidate chemotherapy drugs are examined
      to determine if they have sufficiently cytotoxic to function as an anti-tumor
      therapeutic. However, the development of molecular targeted drugs is based on
      more logical methodologies. First, the target is determined then a search is
      conducted for molecules able to inhibit the target molecule. Some molecular
      targeting drugs, such as Glivec (Imatinib, STI571), have shown amazing effects
      when compared to currently used chemotherapy drugs, whereas few others have
      completely failed to inhibit tumor development in clinical trials. Thus, an
      efficient method for finding effective molecular targeted drugs is needed. An
      important question is whether the target molecule is responsible for tumor growth
      or metastasis. In addition, the clinical administration schedule must be suitable
      for the component used. The drugs will not be completely successful in clinical
      trials if any of the key points are overlooked. Translational studies are
      necessary for a complete evaluation of molecular targeted drugs and, based on the
      results observed in clinical applications, the testers must return to their basic
      laboratory if necessary and improve the drugs for more advanced therapy. In this
      review we discuss on the current and future status of molecular target drugs.

PMID- 17504127
TI  - Carbonic anhydrases as drug targets--an overview.
AB  - At least 15 different alpha-carbonic anhydrase (CA, EC 4.2.1.1) isoforms were
      isolated in mammals, where these zinc enzymes play crucial physiological roles.
      Some of these isozymes are cytosolic (CA I, CA II, CA III, CA VII, CA XIII),
      others are membrane-bound (CA IV, CA IX, CA XII, CA XIV and CA XV), CA VA and CA
      VB are mitochondrial, and CA VI is secreted in saliva and milk. Three acatalytic
      forms are also known, the CA related proteins (CARP), CARP VIII, CARP X and CARP
      XI. Representatives of the beta - delta-CA family are highly abundant in plants,
      diatoms, eubacteria and archaea. These enzymes are very efficient catalysts for
      the reversible hydration of carbon dioxide to bicarbonate, but at least the alpha
      CAs possess a high versatility, being able to catalyze different other hydrolytic
      processes The catalytic mechanism of the alpha-CAs is understood in detail: the
      active site consists of a Zn(II) ion co-ordinated by three histidine residues and
      a water molecule/hydroxide ion. The latter is the active species, acting as a
      potent nucleophile. For beta- and gamma-CAs, the zinc hydroxide mechanism is
      valid too, although at least some beta-class enzymes do not have water directly
      coordinated to the metal ion. CAs are inhibited primarily by two classes of
      compounds: the metal complexing anions (such as cyanide, cyanate, thiocyanate,
      azide, hydrogensulfide, etc) and the sulfonamides/sulfamates/sulfamides
      possessing the general formula RXSO(2)NH(2) (R = aryl; hetaryl; perhaloalkyl; X =
      nothing, O or NH). Several important physiological and physio-pathological
      functions are played by the CA isozymes present in organisms all over the
      phylogenetic tree, related to respiration and transport of CO(2)/bicarbonate
      between metabolizing tissues and the lungs, pH and CO(2) homeostasis, electrolyte
      secretion in a variety of tissues/organs, biosynthetic reactions, such as the
      gluconeogenesis and ureagenesis among others (in animals), CO(2) fixation (in
      plants and algae), etc. The presence of these ubiquitous enzymes in so many
      tissues and in so different isoforms, represents an attractive goal for the
      design of inhibitors with biomedical applications. Indeed, CA inhibitors are
      clinically used as antiglaucoma drugs, some other compounds being developed as
      antitumor agents/diagnostic tools for tumors, antiobesity agents,
      anticonvulsants, and antimicrobials/antifungals (inhibitors targeting CAs from
      pathogenic organisms such as Helicobacter pylori, Mycobacterium tuberculosis,
      Plasmodium falciparum, Candida albicans, etc).

PMID- 17504128
TI  - Metal binding functions in the design of carbonic anhydrase inhibitors.
AB  - The carbonic anhydrases (CAs, EC 4.2.1.1) are zinc containing metalloenzymes
      which catalyse efficiently the reversible hydration of carbon dioxide to
      bicarbonate with discharge of a proton, playing important physiological and
      physiopathological functions. To date, 16 different carbonic anhydrase isoforms
      have been described in higher vertebrates, including humans, and some of them
      have been considered as important targets for inhibitors with therapeutic
      applications. The catalytic and structural role of zinc in these enzyme are
      understood in great detail, and this provided molecular basis for the design of
      potent inhibitors, some of which possessing important clinical applications
      mainly as topically acting anti-glaucoma drugs, anticancer or antiobesity agents.
      The metal binding function is a critically important factor in the development of
      isozyme-specific and organ-selective inhibitors. Discovery of compounds that
      possess zinc binding function different from that of the classical one
      (sulfonamide type) is in constant progress and can offer opportunities for
      developing novel pharmacological agents. In the present review we will discuss
      the different zinc binding function reported in the literature up to now in the
      design of carbonic anhydrase inhibitors.

PMID- 17504129
TI  - The development of topically acting carbonic anhydrase inhibitors as anti
      glaucoma agents.
AB  - Carbonic anhydrase inhibitors (CAIs) such as acetazolamide, methazolamide,
      ethoxzolamide and dichlorophenamide were and still are widely used systemic
      antiglaucoma drugs. Their mechanism of action consists in inhibition of CA
      isozymes present in ciliary processes of the eye (such as CA II, IV and XII),
      with the consequent reduction of bicarbonate and aqueous humour secretion, and of
      elevated intraocular pressure (IOP) characteristic of this disease. Since CA
      II/IV/XII are present in many other tissues/organs, generally, systemic CAIs
      possess undesired side effects such as numbness and tingling of extremities;
      metallic taste; depression; fatigue; malaise; weight loss; decreased libido;
      gastrointestinal irritation; metabolic acidosis; renal calculi and transient
      myopia. In order to avoid these undesired side effects, recently, topically
      effective CAIs have been developed. Two drugs are available clinically:
      dorzolamide and brinzolamide. Both these drugs are applied topically as water
      solutions/suspensions, alone or in combination with other agents (such as beta
      blockers, prostaglandin derivatives, etc) and produce a consistent and prolonged
      reduction of IOP. Furthermore, recent reports show both the systemically as well
      as topically acting sulfonamide CAIs to be effective in the treatment of macular
      oedema and other macular degeneration diseases, for which pharmacological
      treatment was unavailable up to now. Much research is in act in the search of
      even more effective topically acting CAIs, free of the inconveniences and side
      effects of the presently available drugs. For achieving this goal, a recently
      reported strategy, the tail approach, was extensively applied for the synthesis
      of large numbers of derivatives possessing various physico-chemical properties.
      Many such new sulfonamides showed promising antiglaucoma activity in animal
      models of the disease.

PMID- 17504130
TI  - Carbonic anhydrase inhibitors as anticonvulsant agents.
AB  - Seizures are one of the most common neurological disorders in clinical medicine.
      Triggering mechanisms by which seizures form remain unclear, but are related to a
      rapid change in ionic composition, including an increase of intracellular
      potassium concentration and pH shifts within the brain. pH buffering of extra-
      and intracellular spaces is mainly carried out by the CO(2)/ HCO(3)(-) buffer,
      the equilibration of the two species being assured by the zinc enzyme carbonic
      anhydrase (CA, EC 4.2.1.1). Some carbonic anhydrase inhibitors (CAIs) are used as
      anticonvulsants in the treatment of epilepsy. In this review, we will describe
      the link between CA and seizures on the basis of several putative mechanisms.
      Several CA isozymes have been pointed out for their contribution to epileptiform
      activity. An overview of the CA isozyme expression in the brain and of their
      specifics roles is also discussed. This article reviews the research achievements
      published on CA inhibitors, clinically used as anticonvulsant and those under
      development.

PMID- 17504125
TI  - Conditionally replicating adenoviruses for cancer treatment.
AB  - Replication-conditional, oncolytic adenoviruses are emerging as powerful tools in
      the warfare on cancer. The ability to modify cell-specific infectivity or tissue
      specific replication machinery, as well as the possibility of modifying viral
      cellular protein interactions with cellular checkpoint regulators are emerging as
      new trends in the design of safer and more effective adenoviruses. The
      integration of oncolytic adenoviruses with mainstream cancer therapies, such as
      chemotherapy and radiotherapy, continues to yield significant therapeutic
      benefits. Adenoviruses can be armed with prodrug-activating enzymes as well as
      tumor suppressor genes or anti-angiogenic factors, thus providing for enhanced
      anti-tumor therapy and reduced host toxicity. Thus far, encouraging results have
      been obtained from extensive preclinical and human clinical studies. However,
      there is a need to improve adenoviral vectors to overcome unresolved problems
      facing this promising anti-cancer agent, chief among these issues is the
      adenovirus-triggered immune response threatening its efficacy. The continued
      expansion of the knowledge base of adenovirus biology will likely lead to further
      improvements in the design of the ideal oncolytic adenoviruses for cancer
      treatment.

PMID- 17504131
TI  - Carbonic anhydrase inhibitors and the management of cancer.
AB  - Recent progress in understanding the role of catalytically active carbonic
      anhydrases in tumors has opened new possibilities for diagnostic and/or
      therapeutic applications of carbonic anhydrase inhibitors selectively blocking
      the enzyme activity of cancer-related isoforms, namely CA IX and CA XII.
      Different classes of inhibitors have been investigated in order to evaluate their
      usefulness as in vivo imaging tools, as modulators of intratumoral pH that
      influences uptake of conventional chemotherapeutics, or as drugs impeding
      survival of tumor cells exposed to physiological stresses including hypoxia and
      acidosis. Here we summarize the most important data related to expression,
      regulation and functional aspects of cancer-related carbonic anhydrases and
      discuss advances in synthesis and preclinical studies of isozyme-selective and
      highly efficient carbonic anhydrase inhibitors.

PMID- 17504132
TI  - Antiobesity carbonic anhydrase inhibitors.
AB  - Few pharmacological approaches for the treatment of obesity exist at this time,
      and most of them are unsatisfactory, whereas this disease is widespread both in
      the developed and developing world. Novel effective approaches are needed for the
      development of antiobesity agents possessing different mechanisms of action. A
      possible new approach for the treatment and prophylaxis of obesity is based on
      the inhibition of carbonic anhydrases (CAs, EC 4.2.1.1), enzymes involved in
      several steps of de novo lipogenesis, both in the mitochondria and the cytosol of
      cells. Topiramate and zonisamide are two antiepileptic drugs that were shown to
      induce persistent weight loss in obese patients, but their mechanism of action is
      largely unknown. We demonstrated strong CA inhibitory properties for these two
      drugs, by means of kinetic studies in solution and X-ray crystallography, against
      several physiologically relevant isoforms, such as CA II, VA and VB. It has been
      proved that topiramate also inhibits lipogenesis in adipocytes, similarly to
      other sulfonamide CA inhibitors investigated earlier. A large number of new
      sulfonamides have been synthesized and assayed as possible inhibitors of CA
      isoforms involved in lipogenesis. This is the beginning of a very new and
      promising approach for the treatment of obesity, with the hope that new compounds
      showing this property will be soon developed and available for clinical use.

PMID- 17504133
TI  - Dual carbonic anhydrase--cyclooxygenase-2 inhibitors.
AB  - Cyclooxygenase is a key enzyme responsible for metabolisation of arachidonic acid
      into prostaglandins and thromboxane. This enzyme is the target of non steroidal
      anti-inflammatory drugs (NSAIDs), used against inflammation and pain. The
      inducible COX-2 was associated with inflammatory conditions, whereas the
      constitutive form (COX-1) was responsible for the beneficial effects of the PGs.
      This observation led to the development of COX-2 inhibitors or "coxibs" of which
      rofecoxib (Vioxx) characterized by a methylsulfone moiety and the sulfonamides
      celecoxib (Celebrex) and valdecoxib (Bextra). Initially described as COX-2
      "selective" inhibitors, recent reports revealed a nanomolar inhibition activity
      of the sulfonamide COX-2 inhibitors for several carbonic anhydrase (CA) isoforms,
      confirmed by X-ray crystal structures for the adducts of celecoxib and valdecoxib
      with isozyme CA II. This dual activity may help to explain differences in
      clinical observation between sulfonamide and methylsulfone COX-2 inhibitors.
      Moreover, the inhibition of CA isozymes, critical for the development and
      invasion of cancer cells, such as CA II, IX and XII, may constitute an important
      mechanism of antitumor action of such sulfonamide compounds.

PMID- 17504134
TI  - Characterization and inhibition of the recently discovered carbonic anhydrase
      isoforms CA XIII, XIV and XV.
AB  - The carbonic anhydrase (CA) protein family consists of twelve active isozymes in
      humans and thirteen in most other mammals. The most recently discovered members
      of this family include cytosolic CA XIII and membrane-bound CAs XIV and XV. In
      this article we will review the characterization and inhibition profiles of these
      isozymes. CA XIII is expressed in the kidney as well as in the gastrointestinal
      and reproductive tracts, and therefore it may have a role in various
      physiological processes. The inhibition studies with CA XIII have shown that this
      isozyme can be inhibited efficiently with some sulfonamide inhibitors, while it
      is resistant to inhibition with chloride and bicarbonate ions. CA XIV is a
      membrane-bound enzyme that is expressed in numerous organs such as the brain,
      kidney, eye, liver and epididymis, where it has a role in the regulation of acid
      base balance. The inhibitory properties of CA XIV have been studied, but no
      specific inhibitors have been found for this isozyme. The membrane-bound CA XV is
      an exceptional member of this protein family, because it is expressed in numerous
      species but absent in humans and chimpanzees. A detailed biochemical
      characterization of this isozyme is under way in our laboratories.

PMID- 17504135
TI  - Inhibition of the archaeal beta-class (Cab) and gamma-class (Cam) carbonic
      anhydrases.
AB  - Five independently evolved classes (alpha-, beta-, gamma-, delta-, zeta-) of
      carbonic anhydrases facilitate the reversible hydration of carbon dioxide to
      bicarbonate of which the alpha-class is the most extensively studied. Detailed
      inhibition studies of the alpha-class with the two main classes of inhibitors,
      sulfonamides and metal-complexing anions, revealed many inhibitors that are used
      as therapeutic agents to prevent and treat many diseases. Recent inhibitor
      studies of the archaeal beta-class (Cab) and the gamma-class (Cam) carbonic
      anhydrases show differences in inhibition response to sulfonamides and metal
      complexing anions, when compared to the alpha-class carbonic anhydrases. In
      addition, inhibition between Cab and Cam differ. These inhibition patterns are
      consistent with the idea that although, alpha-, beta-, and gamma-class carbonic
      anhydrases participate in the same two-step isomechanism, diverse active site
      architecture among these classes predicts variations on the catalytic mechanism.
      These inhibitor studies of the archaeal beta- and gamma-class carbonic anhydrases
      give insight to new applications of current day carbonic anhydrase inhibitors, as
      well as direct research to develop new compounds that may be specific inhibitors
      of prokaryotic carbonic anhydrases.

PMID- 17504136
TI  - Malarial parasite carbonic anhydrase and its inhibitors.
AB  - Plasmodium falciparum is responsible for the majority of life-threatening cases
      of human malaria. The global emergence of drug-resistant malarial parasites
      necessitates identification and characterization of novel drug targets. At
      present, carbonic anhydrase (CA) genes are identified in limited numbers of
      protozoa and helminthes parasites, however, they are demonstrated in at least 4
      Plasmodium species. The CA gene of P. falciparum encodes an alpha-carbonic
      anhydrase enzyme possessing catalytic properties distinct of that of the human
      host enzymes. A small library of aromatic sulfonamides, most of which were
      Schiff's bases derived from sulfanilamide/homosulfanilamide/4
      aminoethylbenzenesulfonamide and substituted-aromatic aldehydes, or ureido
      substituted sulfonamides are good inhibitors of P. falciparum enzyme. The 4-(3,4
      dichlorophenylureido-ethyl)-benzenesulfonamide is the most effective antimalarial
      activity against growth of P. falciparum in vitro. The nature of the groups
      substituting the aromatic-ureido- or aromatic-azomethine fragment of the molecule
      and the length of the parent sulfonamide (i.e., from sulfanilamide to 4
      aminoethylbenzenesulfonamide) from which the Schiff's base obtained, are the
      critical parameters for the CA inhibitory activities of these aromatic
      sulfonamide derivatives, both against the malarial as well as human enzymes.
      Thus, the sulfonamide CA inhibitors may have the potential for the development of
      novel antimalarial drugs.

PMID- 17504137
TI  - Combined biomarkers for early Alzheimer disease diagnosis.
AB  - Few public health problems have captured the attention of the biomedical and lay
      communities alike as has Alzheimer Disease (AD). Several questions remain still
      open in disease management, as the necessity to delineate disease process from
      "normal ageing". In the last few years, Mild Cognitive Impairment (MCI) has
      received significant attention, thus it represents the major risk factor for AD.
      Not all people diagnosed as having MCI, however, will develop AD, hence there is
      a need to reliably predict progression. To this aim, different biomarkers have
      been proposed with the attempt to identify MCI people who already have pre
      clinical AD. Neuropsychological assessment, peripheral and CSF biomarkers as well
      as neuroimaging findings (both structural and functional) have reported variable
      accuracy values, but better results have been obtained by combined biomarker
      approach. In this review, we summarise the most recent findings on combined
      biomarkers and their usefulness in clinical practice for the early and
      preclinical diagnosis of AD.

PMID- 17504138
TI  - Modulation of transcription by PARP-1: consequences in carcinogenesis and
      inflammation.
AB  - Post-translational modification of proteins by poly(ADP-ribosyl)ation is involved
      in the regulation of a number of biological functions. While an 18 member
      superfamily of poly(ADP-ribose) polymerases (PARP)s has been described PARP-1
      accounts for more than 90% of the poly(ADP-ribosyl)ating capacity of the cells.
      PARP-1 act as a DNA nick sensor and is activated by DNA breaks to cleave NAD(+)
      into nicotinamide and ADP-ribose to synthesize long branching poly(ADP-ribose)
      polymers (PAR) covalently attached to nuclear acceptor proteins. Whereas
      activation of PARP-1 by mild genotoxic stimuli facilitate DNA repair and cell
      survival, severe DNA damage triggers different pathways of cell death including
      PARP-mediated cell death through the translocation of apoptosis inducing factor
      (AIF) from the mitochondria to the nucleus. PAR and PARP-1 have also been
      described as having a function in transcriptional regulation through their
      ability to modify chromatin-associated proteins and as a cofactor of different
      transcription factors, most notably NF-kappaB and AP-1. Pharmacological
      inhibition or genetic ablation of PARP-1 not only provided remarkable protection
      from tissue injury in various oxidative stress-related disease models but it
      result in a clear benefit in the treatment of cancer by different mechanisms
      including selective killing of homologous recombination-deficient tumor cells,
      down regulation of tumor-related gene expression and decrease in the apoptotic
      threshold in the co-treatment with chemo and radiotherapy. We will summarize in
      this review the current findings and concepts for the role of PARP-1 and poly(ADP
      ribosyl)ation in the regulation of transcription, oxidative stress and
      carcinogenesis.

PMID- 17504139
TI  - Microglial activation and its implications in the brain diseases.
AB  - An inflammatory process in the central nervous system (CNS) is believed to play
      an important role in the pathway leading to neuronal cell death in a number of
      neurodegenerative diseases including Parkinson's disease, Alzheimer's disease,
      prion diseases, multiple sclerosis and HIV-dementia. The inflammatory response is
      mediated by the activated microglia, the resident immune cells of the CNS, which
      normally respond to neuronal damage and remove the damaged cells by phagocytosis.
      Activation of microglia is a hallmark of brain pathology. However, it remains
      controversial whether microglial cells have beneficial or detrimental functions
      in various neuropathological conditions. The chronic activation of microglia may
      in turn cause neuronal damage through the release of potentially cytotoxic
      molecules such as proinflammatory cytokines, reactive oxygen intermediates,
      proteinases and complement proteins. Therefore, suppression of microglia-mediated
      inflammation has been considered as an important strategy in neurodegenerative
      disease therapy. Several anti-inflammatory drugs of various chemical ingredients
      have been shown to repress the microglial activation and to exert neuroprotective
      effects in the CNS following different types of injuries. However, the molecular
      mechanisms by which these effects occur remain unclear. In recent years, several
      research groups including ours have attempted to explain the potential mechanisms
      and signaling pathways for the repressive effect of various drugs, on activation
      of microglial cells in CNS injury. We provide here a comprehensive review of
      recent findings of mechanisms and signaling pathways by which microglial cells
      are activated in CNS inflammatory diseases. This review article further
      summarizes the role of microglial cells in neurodegenerative diseases and various
      forms of potential therapeutic options to inhibit the microglial activation which
      amplifies the inflammation-related neuronal injury in neurodegenerative diseases.

PMID- 17504140
TI  - Molecular anatomy of the brain endothelial barrier: an overview of the
      distributional features.
AB  - The blood-brain barrier (BBB) impedes the influx of intravascular compounds from
      the blood to the brain. The elements composing the BBB are endothelial cells,
      pericytes and the end-feet of astrocytes. Among them, the endothelial cell
      barrier line is the most critical for preventing toxic substances from entering
      the brain. In this review, we focus on the ultrastructural distribution of
      important components in the intracellular junction and cytoplasm of brain
      endothelial cells. The ultrastructural distribution of tight junction-specific
      integral membrane proteins such as occludin, junctional adhesion molecules,
      claudin, peripheral zonula occludens protein-1 (ZO-1), adherens junction-specific
      transmembrane protein cadherin, and adherens junction-associated peripheral
      proteins alpha-catenin, beta-catenin, and p120 catenin is reviewed. P
      glycoprotein and some other transporters recently discovered in endothelial cells
      prevent several compounds from entering the brain parenchyma. It is likely that
      the transient inhibition of P-glycoprotein by antidepressants enables other
      medicines to enter the brain. Vesicular transport with clathrin-mediated or
      adsorptive endocytosis through endothelial cells is also critical for
      transportation of blood-born substances from the bloodstream to the brain. How
      medicines pass the BBB to reach the brain parenchyma is discussed.

PMID- 17504141
TI  - Current developments in the synthesis and biological activity of HIV-1 double
      drug inhibitors.
AB  - A combination of different HIV inhibitors into a single molecular entity is a
      strategy that is growing in popularity in HIV-chemotherapy research. The high
      levels of resistance elicited by both nucleoside and non-nucleoside reverse
      transcriptase inhibitors has prompted the design of double-drugs combining these
      two entities with the aim of addressing the emergence of resistance. The strategy
      involves combining two different inhibitors into a single chemical entity via a
      linker, with the aim of improving the physicochemical characteristics of the
      individual compounds. Linkers may be sub-divided into cleavable and non
      cleavable. While the former result in regeneration of the parent drugs of the
      double-drug once in the cell cytoplasm, the latter type is designed to allow the
      double-drug to target two active sites in a simultaneous or bifunctional fashion,
      which are located in close proximity. The linkers have been attached at the C-5',
      C-5 or N-3 positions of the nucleoside, and in some of the substrates
      synthesized, a synergistic anti-HIV activity has been observed. This review
      focuses on the design and synthesis of anti-HIV double-drugs reported to date.

PMID- 17504142
TI  - A false paradise - mixed blessings in the protein universe: the amyloid as a new
      challenge in drug development.
AB  - Significant advances in therapeutic applications of proteins and peptides have
      brought new challenges in the field of drug development. Ordered protein
      aggregation known as amyloid formation has recently emerged as a universal
      phenomenon due to extensive research in protein folding and amyloid diseases. The
      amyloid represents a new generic structure characterized by cross-beta-sheet
      formation in its core, which implies that any polypeptide can adopt this
      conformation under amyloid-prone conditions. Some widely-used biopharmaceuticals
      such as insulin, glucagon, amylin and calcitonin have been shown to form amyloids
      and this list may be significantly extended upon further research. Compared to
      soluble precursor proteins and amorphous aggregates amyloids gain new properties
      such as remarkable stability and protease resistance, polymorphism, self
      propagation via seeding and cross-seeding, cytotoxicity and induced
      immunogenicity. Some of them can be hazardous in biopharmaceutical applications.
      The causes of amyloid aggregation and strategies for its prevention are reviewed
      here. They utilize the current knowledge of amyloid properties, structure-based
      design principles and protein chemistry. Once these challenges are met, they will
      ultimately lead to safer and surer pharmaceuticals.

PMID- 17504143
TI  - The nuclear envelope, a key structure in cellular integrity and gene expression.
AB  - The envelope that encapsulates the cell nucleus has recently gained considerable
      interest, as several clinical syndromes are linked to mutations in its molecular
      components. Most disorders recognized so far are caused by defects in the nuclear
      lamins, building blocks of a filamentous network lining the nucleoplasmic side of
      the inner nuclear membrane. Nuclear lamins are the evolutionary precursors of
      cytoskeletal intermediate filaments and associate in a head-to-tail manner into a
      stable lamina at the nuclear periphery and into a more dispersed structure in the
      nucleoplasm. Lamins have a scaffolding function for several nuclear processes
      such as transcription, chromatin organization and DNA replication, and maintain
      nuclear and cellular integrity. Mutations in the LMNA gene, encoding A-type
      lamins, can cause cardiac and skeletal muscle disease, lipodystrophy and
      premature ageing phenotypes. Hence, the integrity of the nuclear envelope seems
      essential for longevity. Furthermore, the laminopathies provide evidence that
      metabolism and ageing are as tightly linked in humans as they are in model
      organisms such as C. elegans. In this review, we elaborate on the structure and
      functions of nuclear lamins, the spectrum of syndromes related to mutations in
      nuclear envelope components and pathogenic concepts unifying these disorders.

PMID- 17504144
TI  - Medicinal chemistry and emerging strategies applied to the development of
      selective estrogen receptor modulators (SERMs).
AB  - Selective estrogen receptor modulators (SERMs), known previously as
      "antiestrogens", are a new category of therapeutic agents used for the prevention
      and treatment of diseases such as osteoporosis and breast cancer. SERMs act as ER
      agonist in some tissues while acting as ER-antagonist in others based on
      conformational change of the receptors, particularly at the helix 12. Currently,
      there are two classes of clinically approved SERMs; triphenylethylene derivatives
      (e.g., tamoxifen) and benzothiophene derivatives (e.g., raloxifene). Tamoxifen,
      raloxifene and toremifene are the most widely used SERMs. Tamoxifen, an
      antagonist of the breast tissue, is the first clinically identified compound with
      noticeable SERM activity. Although tamoxifen has been very successful in breast
      cancer treatment, its agonistic effect on the uterus is said to be associated
      with increase risk of developing endometrial cancer. Ideally, it is presumed that
      SERMs should selectively act as an agonist in the bone and brain while
      simultaneously acting as an antagonist in the breast and uterus. Therefore, the
      therapeutic goal of SERMs is the prevention of estrogen deficiency diseases
      without promoting estrogen-associated tumor growth. Therefore, the objective of
      this review is to summarize various effects that have been applied in improving
      the tissue-selectivity of SERMs, highlighting the emerging understanding of their
      mechanism of actions in selected target tissues and the development of the SERMs.
      The significance in recent discovery of selective estrogen receptor alpha
      modulators, SERAMs will also be reviewed.

PMID- 17504145
TI  - Role of micafungin in the antifungal armamentarium.
AB  - Serious infections caused by opportunistic molds remain a major problem for
      public health. Immune deficiency following organ transplantation and aggressive
      cancer treatment has greatly increased the incidence of systemic mycoses, and
      invasive aspergillosis in patients with AIDS is associated with significant
      morbidity and mortality. Amphotericin B is the first-line therapy for systemic
      infection because of its broad-spectrum and fungicidal activity. However,
      considerable side effects limit its clinical utility. The echinocandins are large
      lipopeptide molecules that inhibit the synthesis of 1,3-beta-D-glucan, a key
      component of the fungal cell wall. Three echinocandins have reached the market,
      and some others are in early clinical development. Caspofungin was the first
      echinocandin to be licensed for clinical use in most countries. Micafungin is
      licensed for clinical use in Japan, China, Taiwan, Jordan, Korea, Hong-Kong and
      the US, and anidulafungin is currently licensed in the US. The novel class of
      echinocandins represents a milestone in antifungal drug research that has further
      expanded our therapeutic options. Studies to date have shown that micafungin
      exhibits extremely potent antifungal activity against clinically important fungi,
      including Aspergillus and azole-resistant strains of Candida. In animal studies,
      micafungin is as efficacious as amphotericin B with respect to improvement of
      survival rate. Micafungin is also characterized by a linear pharmacokinetic
      profile and substantially fewer toxic effects. Micafungin is a poor substrate for
      the cytochrome P450 enzymes, and compared to azoles, fewer drug interactions are
      described. No dose adjustments of the drug are required in the presence of
      mycophenolate mofetil, cyclosporin, tacrolimus, prednisolone, or sirolimus.
      Strategies using this new echinocandin agent will benefit a large number of
      patients with severe immune dysfunction.

PMID- 17504147
TI  - Mathematical modeling of cell adhesion in shear flow: application to targeted
      drug delivery in inflammation and cancer metastasis.
AB  - Cell adhesion plays a pivotal role in diverse biological processes that occur in
      the dynamic setting of the vasculature, including inflammation and cancer
      metastasis. Although complex, the naturally occurring processes that have evolved
      to allow for cell adhesion in the vasculature can be exploited to direct drug
      carriers to targeted cells and tissues. Fluid (blood) flow influences cell
      adhesion at the mesoscale by affecting the mechanical response of cell membrane,
      the intercellular contact area and collisional frequency, and at the nanoscale
      level by modulating the kinetics and mechanics of receptor-ligand interactions.
      Consequently, elucidating the molecular and biophysical nature of cell adhesion
      requires a multidisciplinary approach involving the synthesis of fundamentals
      from hydrodynamic flow, molecular kinetics and cell mechanics with
      biochemistry/molecular cell biology. To date, significant advances have been made
      in the identification and characterization of the critical cell adhesion
      molecules involved in inflammatory disorders, and, to a lesser degree, in cancer
      metastasis. Experimental work at the nanoscale level to determine the lifetime,
      interaction distance and strain responses of adhesion receptor-ligand bonds has
      been spurred by the advent of atomic force microscopy and biomolecular force
      probes, although our current knowledge in this area is far from complete.
      Micropipette aspiration assays along with theoretical frameworks have provided
      vital information on cell mechanics. Progress in each of the aforementioned
      research areas is key to the development of mathematical models of cell adhesion
      that incorporate the appropriate biological, kinetic and mechanical parameters
      that would lead to reliable qualitative and quantitative predictions. These
      multiscale mathematical models can be employed to predict optimal drug carrier
      cell binding through isolated parameter studies and engineering optimization
      schemes, which will be essential for developing effective drug carriers for
      delivery of therapeutic agents to afflicted sites of the host.

PMID- 17504148
TI  - Prognostic models in hepatocellular carcinoma (HCC) and statistical methodologies
      behind them.
AB  - Hepatocellular carcinoma (HCC) is estimated to be responsible for 250,000 deaths
      worldwide yearly. Aggressive surgical resection or liver transplantation still
      remain the only viable curative options for patients suffering the disease
      despite the multitude of emerging therapies for HCC. However, even with the most
      aggressive surgical intervention, survival varies widely within each particular
      stage of HCC. In order to improve utilization of available therapeutic
      modalities, a number of outcome prognostic models have been developed. This
      manuscript reviews the prognostic models most commonly utilized in clinical
      practice and the statistical methodologies on which these models are based. A
      multitude of statistical and mathematical techniques can be used for prognostic
      model development. The most common methodologies used for HCC prognostic model
      development can be generally divided into four groups: survival, artificial
      neural networks, analysis of variance, and cluster analysis. Survival
      methodologies (such as Cox proportional hazard model) are commonly employed for
      estimation of relative significance of risk factors for patient survival or
      cancer recurrence. Artificial neural networks (such as back-propagation network)
      can be supreme approximation tools for any continuous or binary function, and as
      such can be employed for prognostication of HCC recurrence (death). Analysis of
      variance and cluster analysis are the most common statistical tools of recently
      evolved microarrays technology, which, in turn, is one of the most promising
      tools available to the cancer researcher.

PMID- 17504149
TI  - Meta analysis of advanced cancer survival data using lognormal parametric
      fitting: a statistical method to identify effective treatment protocols.
AB  - We describe the use of a parametric lognormal model to calculate and compare
      survival statistics in the clinical treatment of advanced/metastatic pancreatic,
      breast and colon cancers. The fit using the lognormal model explained greater
      than 90% (R(2) ranged from 0.917 to 0.998 for a total of the 51 arms from
      published studies) of the variation in the cumulative survival statistics of
      patients treated for advanced cancers. A meta-analytic Q-test was performed to
      test whether there were significant differences between different studies. For
      all three cancer types, the Q-test showed highly significant differences between
      the survival arms (p<0.0001 for pancreatic, breast and colon cancers). The z
      values expressed the difference of the average of lognormal means relative to
      each study in terms of deviation expressed in standard errors. The treatments
      that were most effective ranked with the highest z-value: Doxorubicin plus
      docetaxel for pancreatic cancer (z-value = 4.1); Capecitabine plus paclitaxel for
      breast cancer (z-value = 3); irinotecan, fluorouracil and folinate for colon
      cancer (z-value = 7.4).

PMID- 17504150
TI  - Appreciation of medical treatments through confidence intervals.
AB  - The typical way of judging about either the efficacy of a new treatment or, on
      the contrary, the damage of a pollutant agent is through a test of hypothesis
      having its ineffectiveness as null hypothesis. This is the typical operational
      field of Kolmogorov's statistical framework where wastes of data (for instance
      non significant deaths in a polluted region) represent the main drawback.
      Instead, confidence intervals about treatment/pollution effectiveness are a way
      of exploiting all data, whatever their number is. We recently proposed a new
      statistical framework, called Algorithmic Inference, for overcoming crucial
      difficulties usually met when computing these intervals and abandoning general
      simplifying hypotheses such as errors' Gaussian distribution. When effectiveness
      is expressed in terms of regression curves between observed data we come to a
      learning problem that we solve by identifying a region where the whole curve lies
      with a given confidence. The approach to inference we propose is very suitable
      for identifying these regions with great accuracy, even in the case of nonlinear
      regression models and/or a limited size of the observed sample, provided that a
      normally powered computing station is available. In the paper we discuss this new
      way of extracting functions from the experimental data and drawing conclusions
      about the treatments originating them. From an operational perspective, we give
      the general layout of the procedure for computing confidence regions as well as
      some applications on real data.

PMID- 17504151
TI  - Mathematical models of behavior of individual animals.
AB  - This review is focused on mathematical modeling of behaviors of a whole organism
      with special emphasis on models with a clearly scientific approach to the problem
      that helps to understand the mechanisms underlying behavior. The aim is to
      provide an overview of old and contemporary mathematical models without complex
      mathematical details. Only deterministic and stochastic, but not statistical
      models are reviewed. All mathematical models of behavior can be divided into two
      main classes. First, models that are based on the principle of teleological
      determinism assume that subjects choose the behavior that will lead them to a
      better payoff in the future. Examples are game theories and operant behavior
      models both of which are based on the matching law. The second class of models
      are based on the principle of causal determinism, which assume that subjects do
      not choose from a set of possibilities but rather are compelled to perform a
      predetermined behavior in response to specific stimuli. Examples are perception
      and discrimination models, drug effects models and individual-based population
      models. A brief overview of the utility of each mathematical model is provided
      for each section.

PMID- 17504152
TI  - Kainate receptors and pain: from dorsal root ganglion to the anterior cingulate
      cortex.
AB  - Ionotropic glutamate receptors contain three subtypes: NMDA, AMPA and kainate
      receptors. The former two receptor subtypes have well defined roles in
      nociception, while the role of kainate receptors in pain is not as well
      characterized. Kainate receptors are expressed in nociceptive pathways, including
      the dorsal root ganglion, spinal cord, thalamus and cortex. Electrophysiological
      studies show that functional kainate receptors are located postsynaptically,
      where they mediate a portion of excitatory synaptic transmission, or are located
      presynaptically, where they modulate excitatory or inhibitory neurotransmission.
      Recent genetic and pharmacological studies suggest that kainate receptors can
      regulate nociceptive responses. These results highlight kainate receptors as a
      target for the development of new treatments for chronic pain.

PMID- 17504154
TI  - Imaging and treatment of oncological diseases.

PMID- 17504155
TI  - The bright future of radionuclides for cancer therapy.
AB  - Originally, nuclear medicine focused on radiopharmaceuticals trapped in organ
      structures, based on their function, and the presence of disease was seen by the
      absence of radioactivity. More recently, target-specific radiopharmaceuticals
      have been developed to visualize and/or treat oncological diseases. Since
      radiopharmaceuticals have historically a leading position in the search for
      "molecular imaging", it would be a waste not to learn from the pitfalls and
      opportunities that have been and are found during the development of
      radiopharmaceuticals. This knowledge can be used in the improvement of contrast
      agents for other imaging modalities like MRI and CT. In this article the aspects
      that are needed for the use of current and future therapeutic and diagnostic
      radiopharmaceuticals are described. Especially the production and development of
      therapeutic and imageable radiopharmaceuticals are demonstrated. MRI or CT can
      sometimes also image stable isotopes of elements that contain useful
      radionuclides. This can result in real multimodality imaging. Combining imaging
      modalities and imaging agents will result in better patient care and can only be
      advantageous if all departments and institutes will collaborate on their research
      work. The combination of approaches together with the fast progress in
      developments in the medical imaging world will result in a bright future for
      imaging driven therapy of cancer.

PMID- 17504153
TI  - Heparin oligosaccharides as potential therapeutic agents in senile dementia.
AB  - Heparin is a glycosaminoglycan mixture currently used in prophylaxis and
      treatment of thrombosis. Heparin possesses non-anticoagulant properties,
      including modulation of various proteases, interactions with fibroblast growth
      factors, and anti-inflammatory actions. Senile dementia of Alzheimer's type is
      accompanied by inflammatory responses contributing to irreversible changes in
      neuronal viability and brain function. Vascular factors are also involved in the
      pathogenesis of senile dementia. Inflammation, endogenous proteoglycans, and
      assembly of senile plagues and neurofibrillary tangles contribute directly and
      indirectly to further neuronal damage. Neuron salvage can be achieved by anti
      inflammation and the competitive inhibition of proteoglycans accumulation. The
      complexity of the pathology of senile dementia provides numerous potential
      targets for therapeutic interventions designed to modulate inflammation and
      proteoglycan assembly. Heparin and related oligosaccharides are known to exhibit
      anti-inflammatory effects as well as inhibitory effects on proteoglycan assembly
      and may prove useful as neuroprotective agents.

PMID- 17504156
TI  - MRI contrast agents: current status and future perspectives.
AB  - Magnetic Resonance Imaging (MRI) is increasingly used in clinical diagnostics,
      for a rapidly growing number of indications. The MRI technique is non-invasive
      and can provide information on the anatomy, function and metabolism of tissues in
      vivo. MRI scans of tissue anatomy and function make use of the two hydrogen atoms
      in water to generate the image. Apart from differences in the local water
      content, the basic contrast in the MR image mainly results from regional
      differences in the intrinsic relaxation times T(1) and T(2), each of which can be
      independently chosen to dominate image contrast. However, the intrinsic contrast
      provided by the water T(1) and T(2) and changes in their values brought about by
      tissue pathology are often too limited to enable a sensitive and specific
      diagnosis. For that reason increasing use is made of MRI contrast agents that
      alter the image contrast following intravenous injection. The degree and location
      of the contrast changes provide substantial diagnostic information. Certain
      contrast agents are predominantly used to shorten the T(1) relaxation time and
      these are mainly based on low-molecular weight chelates of the gadolinium ion
      (Gd(3+)). The most widely used T(2) shortening agents are based on iron oxide
      (FeO) particles. Depending on their chemical composition, molecular structure and
      overall size, the in vivo distribution volume and pharmacokinetic properties vary
      widely between different contrast agents and these largely determine their use in
      specific diagnostic tests. This review describes the current status, as well as
      recent and future developments of MRI contrast agents with focus on applications
      in oncology. First the basis of MR image contrast and how it is altered by
      contrast agents will be discussed. After some considerations on bioavailability
      and pharmacokinetics, specific applications of contrast agents will be presented
      according to their specific purposes, starting with non-specific contrast agents
      used in classical contrast enhanced magnetic resonance angiography (MRA) and
      dynamic contrast enhanced MRI. Next targeted contrast agents, which are actively
      directed towards a specific molecular target using an appropriate ligand,
      functional contrast agents, mainly used for functional brain and heart imaging,
      smart contrast agents, which generate contrast as a response to a change in their
      physical environment as a consequence of some biological process, and finally
      cell labeling agents will be presented. To conclude some future perspectives are
      discussed.

PMID- 17504157
TI  - Contrast agents in X-ray computed tomography and its applications in oncology.
AB  - Intravascular iodinated contrast agents are required for a large proportion of
      computed tomography (CT) studies. Contrast media are indispensable to more
      clearly differentiate anatomic structures and to detect and characterize
      abnormalities. Depending on the indication up to 200 ml of these agents are
      injected during CT. Despite these large amounts adverse effects are rare and have
      further decreased with the introduction of non-ionic substances. However, it took
      10 to 20 years until these non-ionic agents replaced the older ionic agents in
      clinical practice. In recent years no new substance has been brought to the
      market. The introduction of rapid scanning using multislice CT technology,
      however, has led to the development of more sophisticated contrast injection
      techniques. Current research focuses on optimizing contrast application
      techniques and on further evaluating the safety profiles of the various
      substances. The amount of contrast enhancement obtained in individual patients
      for instance depends on the contrast agent characteristics, such as iodine
      concentration, and the parameters of the contrast injection protocol, such as
      iodine flux and iodine dose. Meanwhile, contrast agent characteristics such as
      osmolality and viscosity play a role in the safety profile of an agent. This
      paper provides a current overview of CT contrast media, CT contrast dynamics, and
      CT contrast applications with a special focus on oncological imaging.

PMID- 17504158
TI  - Factors affecting the sensitivity and detection limits of MRI, CT, and SPECT for
      multimodal diagnostic and therapeutic agents.
AB  - Noninvasive imaging techniques like magnetic resonance imaging (MRI), computed
      tomography (CT) and single photon emission computed tomography (SPECT) play an
      increasingly important role in the diagnostic workup and treatment of cancerous
      disease. In this context, a distinct trend can be observed towards the
      development of contrast agents and radiopharmaceuticals that open up perspectives
      on a multimodality imaging approach, involving all three aforementioned
      techniques. To promote insight into the potentialities of such an approach, we
      prepared an overview of the strengths and limitations of the various imaging
      techniques, in particular with regard to their capability to quantify the spatial
      distribution of a multimodal diagnostic agent. To accomplish this task, we used a
      two-step approach. In the first step, we examined the situation for a particular
      therapeutic anti-cancer agent with multimodal imaging opportunities, viz. holmium
      loaded microspheres (HoMS). Physical phantom experiments were performed to enable
      a comparative evaluation of the three modalities assuming the use of standard
      equipment, standard clinical scan protocols, and signal-known-exactly conditions.
      These phantom data were then analyzed so as to obtain first order estimates of
      the sensitivity and detection limits of MRI, CT and SPECT for HoMS. In the second
      step, the results for HoMS were taken as a starting point for a discussion of the
      factors affecting the sensitivity and detection limits of MRI, CT and SPECT for
      multimodal agents in general. In this, emphasis was put on the factors that must
      be taken into account when extrapolating the findings for HoMS to other
      diagnostic tasks, other contrast agents, other experimental conditions, and other
      scan protocols.

PMID- 17504159
TI  - Radionuclide therapy of cancer with radiolabeled antibodies.
AB  - Radioimmunotherapy (RIT) using radiolabeled monoclonal antibodies (MAbs) directed
      against tumor-associated antigens has evolved from an appealing concept to one of
      the standard treatment options for patients with non-Hodgkin's lymphoma (NHL).
      Inefficient localization of radiolabeled MAbs to nonhematological cancers due to
      various tumor-related factors, however, limits the therapeutic efficacy of RIT in
      solid tumors. Still, small volume or minimal residual disease has been recognized
      as a potentially suitable target for radiolabeled antibodies. Several strategies
      are being explored aimed at improving the targeting of radiolabeled MAbs to solid
      tumors thus improving their therapeutic efficacy. In this review, various aspects
      of the application of radiolabeled MAbs as anti-cancer agents are discussed, and
      the clinical results of RIT in patients with hematological and various solid
      cancers (colorectal, ovarian, breast and renal carcinomas) are reviewed.

PMID- 17504160
TI  - Radiolabelled regulatory peptides for imaging and therapy.
AB  - Radiolabelled peptides have shown to be an important class of
      radiopharmaceuticals for imaging and therapy of malignancies expressing receptors
      of regulatory peptides. These peptides have high affinity and specificity for
      their receptors. The majority of these receptors are present at different levels
      in different tissues and tumours. This review focuses on the application of
      regulatory peptides radiolabelled with (67/68)Ga, (90)Y, (111)In or (177)Lu. Due
      attention is given to the current status of research, limitations and future
      perspectives of the application of these radiolabelled peptides for imaging and
      radiotherapy. It also covers elements of the basic science and preclinical and
      clinical aspects in general, however, mostly based on somatostatin receptor
      mediated imaging and therapy. New analogues, chelators, radionuclides and
      combinations thereof are discussed.

PMID- 17504161
TI  - Targeting the ubiquitin-proteasome pathway in cancer therapy.
AB  - The ubiquitin-proteasome pathway plays a central role in the degradation of
      proteins involved in several pathways including the cell cycle, cellular
      proliferation and apoptosis. Bortezomib is the first proteasome inhibitor to
      enter clinical use, and received approval by the Food and Drug Administration
      (FDA) for the treatment of patients with multiple myeloma, therefore validating
      inhibition of the proteasome as an anticancer target. The approval of Bortezomib
      was based on a large, international, multicenter phase III trial showing its
      efficacy and safety compared with conventional therapy. Preclinical data also
      demonstrates the synergistic effect of bortezomib with other chemotherapeutic
      agents and its ability to overcome drug resistance. Since then several other
      proteasome inhibitors have been developed. The anti-tumor activities of
      bortezomib have been attributed to its effect on pro-apoptotic pathways including
      the inhibition of NF-kappaB and induction of endoplasmic reticulum stress.
      However, the molecular mechanisms are not fully understood. In this review, we
      will summarize the molecular mechanism of apoptosis by bortezomib.

PMID- 17504164
TI  - Bio-basis function neural networks in protein data mining.
AB  - Accurately identifying functional sites in proteins is one of the most important
      topics in bioinformatics and systems biology. In bioinformatics, identifying
      protease cleavage sites in protein sequences can aid drug/inhibitor design. In
      systems biology, post-translational protein-protein interaction activity is one
      of the major components for analyzing signaling pathway activities. Determining
      functional sites using laboratory experiments are normally time consuming and
      expensive. Computer programs have therefore been widely used for this kind of
      task. Mining protein sequence data using computer programs covers two major
      issues: 1) discovering how amino acid specificity affects functional sites and 2)
      discovering what amino acid specificity is. Both need a proper coding mechanism
      prior to using a proper machine learning algorithm. The development of the bio
      basis function neural network (BBFNN) has made a new way for protein sequence
      data mining. The bio-basis function used in BBFNN is biologically sound in well
      coding biological information in protein sequences, i.e. well measuring the
      similarity between protein sequences. BBFNN has therefore been outperforming
      conventional neural networks in many subjects of protein sequence data mining
      from protease cleavage site prediction to disordered protein identification. This
      review focuses on the variants of BBFNN and their applications in mining protein
      sequence data.

PMID- 17504162
TI  - Labeling biomolecules with radiorhenium: a review of the bifunctional chelators.
AB  - For radiotherapy, biomolecules such as intact antibodies, antibody fragments,
      peptides, DNAs and other oligomers have all been labeled with radiorhenium
      ((186)Re and (188)Re). Three different approaches have been employed that may be
      referred to as direct, indirect and integral labeling. Direct labeling applies to
      proteins and involves the initial reduction of endogenous disulfide bridges to
      provide chelation sites. Indirect labeling can apply to most biomolecules and
      involves the initial attachment of an exogenous chelator. Finally, integral
      labeling is a special case applying only to small molecules in which the metallic
      radionuclide serves to link two parts of a biomolecule together in forming the
      labeled complex. While the number of varieties for the direct and integral
      radiolabeling approaches is rather limited, a fairly large and diverse number of
      chelators have been reported in the case of indirect labeling. Our objective
      herein is to provide an overview of the various chelators that have been used in
      the indirect labeling of biomolecules with radiorhenium, including details on the
      labeling procedures, the stability of the radiolabel and, where possible, the
      influence of the label on biological properties.

PMID- 17504165
TI  - Computational and experimental approaches for modeling gene regulatory networks.
AB  - To understand most cellular processes, one must understand how genetic
      information is processed. A formidable challenge is the dissection of gene
      regulatory networks to delineate how eukaryotic cells coordinate and govern
      patterns of gene expression that ultimately lead to a phenotype. In this paper,
      we review several approaches for modeling eukaryotic gene regulatory networks and
      for reverse engineering such networks from experimental observations. Since we
      are interested in elucidating the transcriptional regulatory mechanisms of colon
      cancer progression, we use this important biological problem to illustrate
      various aspects of modeling gene regulation. We discuss four important models:
      gene networks, transcriptional regulatory systems, Boolean networks, and
      dynamical Bayesian networks. We review state-of-the-art functional genomics
      techniques, such as gene expression profiling, cis-regulatory element
      identification, TF target gene identification, and gene silencing by RNA
      interference, which can be used to extract information about gene regulation. We
      can employ this information, in conjunction with appropriately designed reverse
      engineering algorithms, to construct a computational model of gene regulation
      that sufficiently predicts experimental observations. In the last part of this
      review, we focus on the problem of reverse engineering transcriptional regulatory
      networks by gene perturbations. We mathematically formulate this problem and
      discuss the role of experimental resolution in our ability to reconstruct
      accurate models of gene regulation. We conclude, by discussing a promising
      approach for inferring a transcriptional regulatory system from microarray data
      obtained by gene perturbations.

PMID- 17504166
TI  - Mechanism of psychoactive drug action in the brain: simulation modeling of GABAA
      receptor interactions at non-equilibrium conditions.
AB  - Synaptic transmission requires that the binding of the transmitter to the
      receptor to occur under rapidly changing transmitter levels, and this binding
      interaction is unlikely to be at equilibrium. We have sought to numerically solve
      for binding kinetics using ordinary differential equations and simultaneous
      difference equations for use in stochastic conditions. The reaction scheme of
      GABA interacting with the ligand-gated ion-channel demonstrates numerical
      stiffness. Implicit methods (Backward Euler, ode23s) performed orders of
      magnitude better than explicit methods (Forward Euler, ode23, RK4, ode45) in
      terms of step size required for stability, number of steps and cpu time.
      Interestingly, upon solving the system of 8 ordinary differential equations for
      the GABA reaction scheme we observed the existence of low dimensional invariant
      manifolds that may have important consequences for information processing in
      synapses. We also describe a mathematical approach that models complex receptor
      interactions in which the timing and amplitude of transmitter release are noisy.
      Exact solutions for simple bimolecular interactions that include stoichiometric
      interactions and receptor transitions can be used to model complex reaction
      schemes. We used the difference method to investigate the information processing
      capabilities of GABA(A) receptors and to predict how pharmacological agents may
      modify these properties. Initial simulations using a model for heterosynaptic
      regulation shows that signal to noise ratios can be decreased in the presence of
      background presynaptic activity both in the presence and absence of
      chlorpromazine. These types of simulations provide a platform for investigating
      the effect of psycho-active drugs on complex responses of transmitter-receptor
      interactions in noisy cellular environments such as the synapse. Understanding
      this process of transmitter-receptor interactions may be useful in the
      development of more specific and highly targeted modes of action.

PMID- 17504167
TI  - Mathematical models of blood coagulation and platelet adhesion: clinical
      applications.
AB  - At present, computer-assisted molecular modeling and virtual screening have
      become effective and widely-used tools for drug design. However, a prerequisite
      for design and synthesis of a therapeutic agent is determination of a correct
      target in the metabolic system, which should be either inhibited or stimulated.
      Solution of this extremely complicated problem can also be assisted by
      computational methods. This review discusses the use of mathematical models of
      blood coagulation and platelet-mediated primary hemostasis and thrombosis as cost
      effective and time-saving tools in research, clinical practice, and development
      of new therapeutic agents and biomaterials. We focus on four aspects of their
      application: 1) efficient diagnostics, i.e. theoretical interpretation of
      diagnostic data, including sensitivity of various clotting assays to the changes
      in the coagulation system; 2) elucidation of mechanisms of coagulation disorders
      (e.g. hemophilias and thrombophilias); 3) exploration of mechanisms of action of
      therapeutic agents (e.g. recombinant activated factor VII) and planning rational
      therapeutic strategy; 4) development of biomaterials with non-thrombogenic
      properties in the design of artificial organs and implantable devices.
      Accumulation of experimental knowledge about the blood coagulation system and
      about platelets, combined with impressive increase of computational power,
      promises rapid development of this field.

PMID- 17504168
TI  - An introduction to recursive neural networks and kernel methods for
      cheminformatics.
AB  - The aim of this paper is to introduce the reader to new developments in Neural
      Networks and Kernel Machines concerning the treatment of structured domains.
      Specifically, we discuss the research on these relatively new models to introduce
      a novel and more general approach to QSPR/QSAR analysis. The focus is on the
      computational side and not on the experimental one.

PMID- 17504169
TI  - Artificial intelligence approaches for rational drug design and discovery.
AB  - Pattern recognition, machine learning and artificial intelligence approaches play
      an increasingly important role in rational drug design, screening and
      identification of candidate molecules and studies on quantitative structure
      activity relationships (QSAR). In this review, we present an overview of basic
      concepts and methodology in the fields of machine learning and artificial
      intelligence (AI). An emphasis is put on methods that enable an intuitive
      interpretation of the results and facilitate gaining an insight into the
      structure of the problem at hand. We also discuss representative applications of
      AI methods to docking, screening and QSAR studies. The growing trend to integrate
      computational and experimental efforts in that regard and some future
      developments are discussed. In addition, we comment on a broader role of machine
      learning and artificial intelligence approaches in biomedical research.

PMID- 17504170
TI  - Effects of highly active antiretroviral therapy on HIV-1-associated oral
      complications.
AB  - The oral cavity of human immunodeficiency virus type I (HIV-1) infected
      individuals is subjected to a series of opportunistic infections which are
      usually considered as a prognostic marker for the severity of infection as well
      as an indicator of immunodeficiency. The highly active antiretroviral therapy
      (HAART) has significantly lessened the severity of HIV-associated oral infections
      although this therapeutic regimen is considered to be responsible for some of the
      oral lesions such as oral warts and salivary gland disorders. In addition, the
      beneficial effects of HAART on HIV associated oral lesions are stratified with
      age, with the adult population showing improvements whereas the oral lesions
      among children remain unchanged with this therapy. The presence of HIV-1 in the
      saliva, and infectivity of oral epithelial cells suggest that the oral cavity is
      a site of HIV pathogenesis and potential reservoir for the disease in the setting
      of virally suppressive HAART. Overall HIV associated oral lesions are usually due
      to fungal, bacterial, and viral infections as well as some of unknown etiology.
      This review describes the current status of HIV associated oral lesions by
      comparing historically available pre-HAART data. Future directions envisioned by
      the National Institutes of Health as well as novel avenues to be explored are
      also presented.

PMID- 17504171
TI  - HIV-1 replication from after cell entry to the nuclear periphery.
AB  - Productive infection with HIV-1 is mediated by fusion of the HIV-1 envelope with
      the cell membrane and subsequent entry of the virion core into the cytoplasm. The
      core is then rearranged to form the reverse transcription complex which is
      responsible for conversion of the genomic RNA to its double-stranded DNA copy.
      Various genetic, biochemical and microscopy studies have shed light on the role
      of viral proteins in the core in this process; Gag cleavage products, in
      particular, are crucial. It is also at this point that core is potentially
      exposed to the action of restriction factors such as TRIM5alpha and APOBEC3G,
      highlighting the vulnerability of this stage of the retrovirus life-cycle to the
      cell's defenses. Rearrangement of the core may be an active process involving
      host-cell activities, although this is not clear, but may also be partly passive
      due to the instability of the structure. What regulates this process is unknown.
      Several host-cell kinase activities are important for replication and have been
      shown to be incorporated in the virion. We speculate that these kinases may
      regulate core rearrangement or the interaction of the reverse transcription
      complex/pre-integration complex with the cytoplasm. Recent real-time microscopy
      experiments with fluorescent-labeled probes suggest a model in which the virion
      utilizes the cytoskeleton for transport whilst in the cytoplasm. After entering
      the cell, the virion interacts initially with actin filaments which assist
      binding to microtubles enabling transport to the nuclear periphery. An actin
      transport process may then facilitate the remaining short journey to the nuclear
      membrane.

PMID- 17504172
TI  - Progress in understanding basal ganglia dysfunction as a common target for
      methamphetamine abuse and HIV-1 neurodegeneration.
AB  - HIV-1 infection with concurrent methamphetamine (MA) abuse results in exacerbated
      neurodegenerative changes and rapid progression of a form of sub-cortical
      dementia termed HIV-1 associated dementia (HAD). A notable feature of HAD is the
      involvement of the dopaminergic system manifested as parkinsonian like movement
      abnormalities. The HIV-1 transactivator of transcription (Tat) protein is very
      often used in experimental studies trying to understand neurotoxic consequences
      of HIV-1 infection, since the pathophysiological changes induced by Tat mirrors,
      in part, the means by which HIV-1 infection of the nervous system results in
      neuronal damage. Understanding the interaction of Tat and MA in the basal ganglia
      and the resultant injury to the dopaminergic system in rodent models as well as
      cell culture will shed light on the dopaminergic pathology occurring in HIV-1
      infected-MA abusers. The aim of this review is to update the reader on the
      current knowledge of MA and HIV-1 neurotoxicity, specifically Tat, and discuss
      the progress in understanding how MA synergizes with the HIV-1 transactivator
      protein Tat to damage the basal ganglia.

PMID- 17504173
TI  - Association of gag multimers with filamentous actin during equine infectious
      anemia virus assembly.
AB  - A role for the actin cytoskeleton in retrovirus assembly has long been
      speculated. However, specific mechanisms by which actin facilitates the assembly
      process remain elusive. We previously demonstrated differential effects of
      experimentally modified actin dynamics on virion production of equine infectious
      anemia virus (EIAV), a lentivirus related to HIV-1, suggesting an involvement of
      actin dynamics in retrovirus production. In the current study, we used
      bimolecular fluorescence complementation (BiFC) to reveal intimate (<15 nm) and
      specific associations between EIAV Gag and actin, but not tubulin. Specific
      interaction between Gag and filamentous actin was also demonstrated by co
      immunoprecipitation experiments combined with the actin severing protein gelsolin
      to solubilize F-actin. Deletion of capsid (CA) or nucleocapsid (NC) genes reduced
      Gag association with F-actin by 40% and 95%, respectively. Interestingly, GCN4, a
      leucine zipper motif, could substitute for the NC domain in mediating F-actin
      association. Furthermore, deficiency of the DeltaNC Gag in F-actin interaction
      was restored upon co-expression of Gag constructs containing both CA and NC or
      the GCN4, suggesting a requirement for Gag polyprotein multimerization prior to F
      actin association. The observed Gag-F-actin association appeared to correlate
      with viral budding, as enhanced budding of the DeltaNC mutant was evident upon
      restoration of F-actin association. Intracellular association of Gag complexes
      with F-actin was also detected by immunoscanning electron microscopy of Triton
      extracted EIAV-infected cells. Together, these data suggest that Gag multimers
      induced by CA and NC domains interact with F-actin and that this association is
      important for efficient virion production.

PMID- 17504174
TI  - Abnormal cytokine production by circulating monocytes and dendritic cells of
      myeloid origin in ART-treated HIV-1+ patients relates to CD4+ T-cell recovery and
      HCV co-infection.
AB  - HIV-1 infection is associated with dysregulation of cytokine production by
      peripheral blood (PB) monocytes and dendritic cells (DC), but controversial
      results have been reported. We aimed to analyze the effect of antiretroviral
      therapy (ART) on the in vitro production of inflammatory cytokines by PB
      stimulated monocytes and DC of myeloid origin -CD33(high+ ) myeloid DC (mDC) and
      CD33(+)/CD14(-/dim+)/CD16(high+) DC- from HIV-1+ patients and its relationship
      with CD4+ T-cell recovery and co-infection with hepatitis C virus (HCV). In vitro
      cytokine production was analyzed at the single cell level in 32 HIV-1+ patients,
      grouped according to the number of CD4+ T-cells/microl in PB (<200 CD4 versus
      >200 CD4). Patients were tested prior to therapy and at weeks +2, +4, +8, +12 and
      +52 after ART. Prior to ART, production of IL-6, TNF-alpha and IL-12 by mDC and
      of IL-8 and IL-12 by CD16+ DC was significantly increased among >200 CD4
      patients. After one year of ART, increased production of IL-8 by monocytes, of
      TNF-alpha by mDC and of IL-1beta, IL-6 and TNF-alpha by CD16+ DC was specifically
      observed among <200 CD4 HIV-1+ individuals showing a high recovery of PB CD4+ T
      cell counts. In turn, we found that the significantly reduced percentage of IL
      1beta, IL-6, IL-8 and TNF-alpha-producing monocytes and of IL-6 and IL-8
      producing mDC and CD16+ DC, as well as the significantly diminished mean amount
      of IL-6 produced per monocyte, mDC and CD16+ DC and of IL-12 produced per CD16+
      DC observed at week +52 for the >200 CD4 patients, were related to the presence
      of co-infection with HCV. In summary, HIV-1+ individuals show abnormal production
      of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin
      even after one year of ART, such abnormalities being associated with the degree
      of recovery of PB CD4+ T-cell counts in more immunocompromised patients and HCV
      co-infection in more immunocompetent HIV-1+ individuals.

PMID- 17504176
TI  - SV40 and HIV sequences in the cerebrospinal fluid of a patient with AIDS dementia
      complex.
AB  - Central Nervous System (CNS) diseases that occur in HIV-positive patients are
      mainly due to HIV itself or to opportunistic microorganisms. Polyomavirus JCV,
      BKV and SV40 have been associated with encephalopathies in both HIV-positive and
      HIV-negative patients. To investigate the presence of Polyomavirus DNA sequences
      in patients affected by CNS disorders, 82 CSF samples from 70 HIV-positive and 12
      HIV-negative patients were analyzed by PCR. A double HIV and SV40 infection was
      found in one patient suffering with AIDS dementia complex. SV40 DNA sequence
      analysis showed the homology with wild type SV40 strain. SV40 should be
      considered as a potential causal agent of CNS disorders in AIDS patients.

PMID- 17504175
TI  - Effects of structured treatment interruptions on metabolic, anthropometric,
      immunologic, and quality of life outcomes in HIV-positive adults on HAART.
AB  - Structured treatment interruptions may have beneficial effects on metabolic
      parameters, while data on anthropometric parameters and on the quality of life
      are scanty. This study was designed to evaluate the effects of structured
      treatment interruptions on plasma cholesterol, triglycerides, anthropometric,
      immunologic, virologic changes and quality of life. A total of 112 HIV-infected
      patients under HAART with undetectable viremia for longer than 6 months were
      randomized to undergo 6 cycles of 1-month off and 1-month on therapy or to
      continue HAART. Patients treated with structured treatment interruptions (STI
      group) were evaluated monthly, patients in the control group (CTRL group) were
      evaluated every two months. Anthropometric and quality of life data were
      collected every four months. The study was designed as a two-arm, prospective,
      multicentred, controlled trial. Results on the primary endpoints showed a
      significant decrease in the cholesterol levels in the STI group compared to the
      CTRL group (total cholesterol median AUC [IQR] was 193.5 mg/dL/month [173.4
      209.4], and 210.8 mg/dL/month [194-242.4], respectively, p=0.0009). Although the
      triglyceride levels were lower in the STI group, the results did not reach
      statistical significance (triglyceride median AUC [IQR] was 166.8 mg/dL/month
      [IQR: 112.5-234.9] in the CTRL group, and 169 [IR: 124.7-256.7] in the STI group;
      p=0.37). As for the secondary endpoints no major differences among groups were
      noted. Cyclic structured treatment interruptions may have a favorable, although
      limited, impact on plasma total cholesterol levels in HIV-infected subjects. No
      modifications of anthropometric and quality of life values were noted.

PMID- 17504177
TI  - Multiple-dose pharmacokinetics of efavirenz with and without the use of
      rifampicin in HIV-positive patients.
AB  - Rifampicin (RIF) decreases serum concentrations of several antiretroviral drugs.
      We carried out a prospective, comparative study to define efavirenz (EFV)
      pharmacokinetics in 16 cases and 13 controls. Cases were HIV and tuberculosis
      (TB) co-infected adults assuming RIF 600 mg once daily and EFV 800 mg once daily.
      Patients on EFV at standard 600 mg dose without RIF were taken as controls. EFV
      levels in plasma were assayed by high-performance liquid chromatography (HLPC)
      predose (C(trough)) and at 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, 16, 18, 22
      and 24 hours post-dose, and pharmacokinetic parameters were determined by non
      compartmental methods. Among cases, 81% were males, mean age was 37 years, 50%
      were Caucasians, mean weight was 64 kg, mean CD4 cell counts and log HIV RNA
      copies were 160/microl and 5.2 /microl, respectively. Cases had a significantly
      higher Cl/F/kg if compared with controls (0.269 +/- 0.12 versus 0.167 + 0.05
      L/h/kg, p<0.01). Otherwise, dose-dependent pharmacokinetic parameters of EFV were
      similar between cases and controls. Interindividual variability was consistently
      higher among TB cases compared to controls for all considered parameters. All
      cases completed combined treatment and no increased EFV toxicity was observed.
      These results suggest that a dose of 800 mg of EFV in association with rifampicin
      may be appropriate for patients of weight > 60 kg in Europe. Therapeutic drug
      monitoring may be beneficial for patients on combination therapy with RIF.

PMID- 17504178
TI  - Impact of antiretroviral therapy on the relapse of cryptococcosis and survival of
      HIV-infected patients with cryptococcal infection.
AB  - BACKGROUND: Cryptococcosis is an opportunistic infection with morbidity and
      mortality in HIV-infected patients. Impact of antiretroviral therapy (ART) on the
      relapse of cryptococcosis and survival of HIV-infected patients with
      cryptococcosis has not been well established. METHODS: A retrospective cohort
      study of HIV-infected patients with cryptococcosis during 1997-2005 was
      conducted. Relapse and survival rates with corresponding risk factors were
      determined. RESULTS: There were 149 patients with a mean age of 33.5+/-7.4 years
      and 57% were male. Median CD4 cell count was 22 cells/mm(3). After exclusion of
      patients who died or were lost to follow-up during the first two weeks, 127
      patients were eligible for the analysis of the effect of ART on relapse and
      survival rates. Of 127 patients, 52 received ART. The demographic data between
      the two groups were similar. Median time of ART initiation after cryptococcal
      diagnosis was 2.6 months. The most frequent ART used was NNRTI-based regimen
      (88.4%). Median CD4 change at six months of ART was 97 cells/mm(3) and 87.9%
      achieved undetectable HIV-RNA. The cumulative 75% survival (free) from relapse
      duration was 10.4 months in no-ART group and 41.9 months in ART group (P<0.01).
      The 75% survival from cryptococcal-related mortality in no-ART group was 6.4
      months whereas >54 months for ART group (P<0.01). In Cox proportional hazards
      model, ART was the only factor that associated with lower relapse and mortality
      rate (P<0.01). CONCLUSIONS: ART significantly reduced relapse and mortality rate
      from cryptococcosis in HIV-infected patients. ART is strongly recommended in this
      population and should not be delayed.

PMID- 17504179
TI  - Correlations between carotid IMT, factor VIII activity level and metabolic
      disturbances: a cardio-vascular risk factor in the HIV positive persons.
AB  - In the HIV infection, the short time-scale between the HIV-induced cardiovascular
      events and the onset of antiretroviral therapy elicits a thrombophilic co-factor
      that worsens the induced atherosclerosis. We compared the factor VIII plasma
      activity, previously implicated in arterial and venous thrombosis, with a
      surrogate marker of atherosclerosis, the carotid intima-media thickness, and with
      the usual atherosclerosis risk factors in 154 HIV infected outpatients. The FVIII
      plasma activity is significantly associated with the carotid intima-media
      thickness and, strongly, with blood glucose and triglycerides levels. A raised
      FVIII plasma activity is an important feature of the metabolic syndrome and a
      putative co-factor of HAART induced cardiovascular events. Thus the prevention of
      the HAART-induced cardio-vascular events should probably not be exclusively
      focused on atherosclerosis but likewise on the thrombus formation process.

PMID- 17504180
TI  - Chirality--a new era of therapeutics.
AB  - To develop the newer pharmaceuticals and to spur the strong growth, being a
      general property of 'handedness', chirality plays a major role. The Easson
      Stedman principle shows the differences in the biological activity between
      enantiomers resulted from selective reactivity of one enantiomer with its
      receptor. It helps to improve the pharmacokinetic properties and to remove
      undesirable side effects by virtue of the unique activity of enantiomers. Racemic
      switching and marketing drug combinations are used as tools for drug life-cycle
      management and to redevelop racemic mixtures as single enantiomers.

PMID- 17504181
TI  - Treatment of organophosphate intoxication using cholinesterase reactivators:
      facts and fiction.
AB  - Basic part of the current standard treatment of organophosphate (OP) agent
      poisoning is administration of cholinesterase reactivators. It includes different
      types of oximes with a similar basic structure differing by the number of
      pyridinium rings and by the position of the oxime group in the pyridinium ring.
      Oximes hydrolytically cleave the organophosphates from acetylcholinesterase
      (AChE), restoring enzymatic function. This reactivation of AChE is dependent on
      the type of the agent and, on the reactivator used. From the common oximes, mono-
      and bisquaternary pyridinium oximes are more or less frequently used in clinical
      practice such as pralidoxime, obidoxime, trimedoxime, and HI-6. Though there are
      data on a good therapeutic effects of reactivators, some attempts to undermine
      the role of reactivators as effective antidotes against OP poisoning have been
      made. Some arguments on the necessity of their administration following OP
      poisoning are discussed with the aim to resolve the question on their effective
      use, possible repeated administration in the treatment of OP poisoning, their
      peripheral and central effects including questions on their penetration through
      the blood brain barrier as well as a possibility to achieve their effective
      concentration for AChE reactivation in the brain. Reactivation of cholinesterases
      in the peripheral and central nervous system is described and it is underlined
      its importance for the survival or death of the organism poisoned with OP. An
      universality of oximes able to reactivate AChE inhibited by all OP is questioned
      and trends (molecular modelling using neural network, structure-activity
      relationship, combination of reactivation and anticholinergic properties in one
      molecule) for future research are characterized.

PMID- 17504182
TI  - Pharmacological therapy of Cushing's syndrome: drugs and indications.
AB  - OBJECTIVE: To review the main pharmacological properties and clinical
      applications of the drugs used in the medical therapy of Cushing's syndrome. DATA
      SOURCES: Search for articles were performed in the following dababases: MEDLINE,
      EMBASE, Cochrane Database of systematic Reviews and The Cochrane Central Register
      of Controlled Trials (CENTRAL). Search terms included Cushing's syndrome and drug
      therapy. DATA SYNTHESIS: Available data suggest that neuromodulatory compounds
      affect corticotropin (ACTH) or ACTH-releasing hormone (CRH) synthesis and
      release. They include serotonin antagonists, dopaminergic agonists, valproic
      acid, reserpine, somatostatin analogs and thiazolidinediones. These agents have
      been effective in a limited number of patients with ACTH-dependent Cushing's
      syndrome. Inhibitors of steroidogenesis reduce cortisol production by blocking
      one (metyrapone, trilostane) or several (aminoglutethimide, ketoconazole,
      fluconazole, etomidate) enzymes involved in steroid biosynthesis. Mitotane is a
      steroidogenesis inhibitor with adrenolitic properties. Mifepriston'e blocks
      glucocorticoid receptor activation without modifying cortisol synthesis.
      CONCLUSION: Agents that inhibit steroidogenesis are useful in all forms of
      Cushing's syndrome and are effective in about 70% of patients. Main indications
      for drug therapy include preparation for surgery, persistence or recurrence after
      surgery, while awaiting for the effect of radiation therapy, occult ectopic ACTH
      syndrome, severe hypercortisolism and malignancy related hypercortisolism.

PMID- 17504183
TI  - Nitrogen-containing heterocyclic quinones: a class of potential selective
      antitumor agents.
AB  - The development of prodrugs that are enzymatically activated into anticancer
      agents is a promising perspective in cancer therapy. Many nitrogen-containing
      quinoid heterocycles have been reported to show antitumor effect. The principal
      interest in these compounds lies on their potential to produce tumor-selective
      toxicity. Selectivity occurs by difference in oxygen tension between normal and
      tumor tissue and by levels of the required activating enzymes. In this review a
      summary of the most interesting heterocyclic quinones is given together with
      their biological property. SAR studies concerning the importance of some
      structural features will be described.

PMID- 17504184
TI  - Rational design of vector and antibiotic peptides using solid-state NMR.
AB  - The application of 2H solid-state NMR in determining structure activity
      relationships and mechanism of action of membrane active peptides is discussed.
      The enhancement of the disruption of anionic lipids in the membrane by new lead
      compounds is shown to be a key determinant of both DNA vector and antimicrobial
      activity.

PMID- 17504185
TI  - Computer-assisted methods in chemical toxicity prediction.
AB  - In Silico predictive ADME/Tox screening of compounds is one of the hottest areas
      in drug discovery. To provide predictions of compound drug-like characteristics
      early in modern drug-discovery decision making, computational technologies have
      been widely accepted to develop rapid high throughput in silico ADMET analysis.
      It is widely perceived that the early screening of chemical entities can
      significantly reduce the expensive costs associated with late stage failures of
      drugs due to poor ADME/Tox properties. Drug toxic effects are broadly defined to
      include toxicity, mutagenicity, carcinogenicity, teratogenicity, neurotoxicity
      and immunotoxicity. Toxicity prediction techniques and structure-activity
      relationships relies on the accurate estimation and representation of physico
      chemical and toxicological properties. This review highlights some of the freely
      and commercially available softwares for toxicity predictions. The information
      content can be utilized as a guide for the scientists involved in the drug
      discovery arena.

PMID- 17504186
TI  - Intraperitoneal chemotherapy as first-line treatment in the management of
      epithelial ovarian cancer.
AB  - Recent evidence has suggested improved outcomes following incorporation of
      intraperitoneal chemotherapy administration with intravenous systemic
      chemotherapy as first-line treatment of small volume residual epithelial ovarian
      cancer. This review focuses on the mechanism of actions of the chemotherapeutic
      drugs and reviews the possible reasons for the superior outcomes of
      intraperitoneal chemotherapy.

PMID- 17504187
TI  - The AMP-activated protein kinase: role in regulation of skeletal muscle
      metabolism and insulin sensitivity.
AB  - Over the past decade, an epidemic of obesity has developed throughout the Western
      World. In recent years, significant interest has focused on the role of the AMP
      activated protein kinase (AMPK) as a potential therapeutic target for the
      treatment of obesity and type 2 diabetes and is such the focus of this review.
      Specifically, the potential role of AMPK in skeletal muscle metabolism as it
      relates to the insulin sensitizing effects of exercise and the hormones, leptin,
      adiponectin, ciliary neurotrophic factor and interleukin-6 are discussed. We
      caution that despite the convincing associations between the activation of AMPK
      signalling and the restoration of insulin sensitivity, future studies in genetic
      models of AMPK deficiency or constitutive activation within skeletal muscle are
      needed to evaluate the quantitative role of AMPK and to validate whether
      strategies designed to activate skeletal muscle AMPK may be important for
      regulating whole-body insulin sensitivity.

PMID- 17504189
TI  - Emerging drugs--potential for misuse in sport and doping control detection
      strategies.
AB  - Preventive doping research includes the development of methods for the detection
      of new or emerging drugs to be implemented in routine screening analysis.
      Candidates with great potential for misuse in elite sports include selective
      androgen receptor modulators, growth hormone secretagogues, hypoxia-inducible
      factor stabilizers and erythropoietin mimetics.

PMID- 17504190
TI  - The role of exhaled nitric oxide in the diagnosis, management and treatment of
      asthma.
AB  - Asthma is a chronic respiratory condition affecting many adults and children. An
      association between asthma and raised gaseous nitric oxide in the exhaled breath
      was first reported in 1993. In the absence of an objective test for diagnosing
      and monitoring asthma, a vigorous research effort has subsequently sought to
      determine the nature of the relationship between exhaled nitric oxide (ENO) and
      asthma and to determine the clinical utility of ENO measurements in asthmatics.
      Many methodological issues relating to ENO measurements have also been addressed.
      The evidence indicates that ENO originates from a number of sources and the
      "excess" ENO in asthmatics is mostly derived from the lower respiratory
      epithelium where ENO probably reflects eosinophilic airway inflammation. Clinical
      studies have revealed that ENO may be useful in the diagnosis of atopic asthma
      but not non-atopic asthma. Longitudinal measurements of ENO have been found to
      correlate with asthma symptoms, including relapse of symptoms after cessation of
      corticosteroids treatment. In summary, over a relatively short time ENO has
      become recognised as a useful objective tool for diagnosing and monitoring
      asthma. More clinical studies will be required in order for ENO to become fully
      established in the diagnosis and management of asthma.

PMID- 17504188
TI  - Genetic variant-associated endothelial dysfunction behind small-vessel cerebral
      circulatory disorders: a new pathomechanism behind common cerebral phenotypes.
AB  - An increasing body of evidence suggests that different genetic factors, such as
      angiotensin-converting enzyme (ACE) I/D, angiotensin II type-1 receptor (AT1R)
      A1166C, methylenetetrahydrofolate reductase (MTHFR) C677T and ENOS G894T variants
      are associated with an endothelial dysfunction (ED). EDs are relatively new
      phenomena that are presumed to contribute to vasoregulatory malfunctions at the
      small-vessel level. Ever more clinical observations indicate that the above
      genetic variants are also associated with cerebral small-vessel disorders. This
      article reviews the knowledge available on the roles of ED- associated genetic
      variants in cerebral circulatory disorders, and suggests that EDs can be
      causative factors for different common cerebral pathologies such as leukoaraiosis
      or/and small-vessel infarcts. Newly-developed drugs involving phosphodiesterase
      type-5 inhibitors, which improve the endothelial functions, may comprise a new
      approach to the treatment and prevention of small-vessel cerebral circulatory
      disorders.

PMID- 17504191
TI  - Molecular and cellular activities of vitamin E analogues.
AB  - Natural vitamin E comprises 8 different analogues, the alpha-, beta-, gamma-, and
      delta-tocopherols and the alpha-, beta-, gamma-, and delta-tocotrienols. However,
      only alpha-tocopherol is selectively enriched by the liver; the other vitamin E
      analogues and also excess alpha-tocopherol are converted to several metabolites
      and eliminated. Recently, a novel phosphorylated form of tocopherol, alpha
      tocopheryl phosphate, was shown to occur naturally in animal and human tissues as
      well as in foods. Several synthetic vitamin E derivatives have been synthesized
      that are either converted by esterases to the natural form, or exert novel or
      vitamin E related biological activities. During the last years, specific cellular
      effects for each individual vitamin E analogue have been described that are the
      consequence of modulating signal transduction and gene expression. These effects
      possibly reflect specific interactions of each of the vitamin E analogues with
      enzymes, structural proteins, lipids and transcription factors. In this review,
      the different natural vitamin E analogues and synthetic derivatives are compiled
      in relation to their major molecular and cellular activities.

PMID- 17504192
TI  - Agaritine and its derivatives are potential inhibitors against HIV proteases.
AB  - Agaritine, or beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine, is a
      Chinese herbal medicine, known having the antiviral and anticancer function.
      However, so far no reports whatsoever have been made for its potential as an anti
      HIV agent. It was observed by docking experiments for more than 9,000 compounds
      extracted from various Chinese medicines that the compound agaritine
      distinguished itself from all the others in binding to the HIV protease with the
      most favorable free energy. Based on this, a series of derivatives were generated
      by modifying agaritine. It has been observed thru an extensive docking study that
      some of agaritine derivatives had markedly stronger binding interaction with the
      HIV protease than agaritine, suggesting that these derivatives might be good
      candidates for developing drugs for AIDS therapy.

PMID- 17504193
TI  - QSAR study on pyridinone derivatives as HIV-1 non-nucleoside reverse
      transcriptase inhibitor: a mixed approach.
AB  - HIV-1 reverse transcriptase inhibitory activity of a series of substituted
      pyridinone derivatives (non-nucleoside) was subjected to classical QSAR study by
      using mixed approach (Hansch and Free-Wilson). The study was carried out with
      indicator parameter encoding different group contributions and some physico
      chemical parameters namely hydrophobic (phi), electronic (sigma), steric (MR) and
      STERIMOL values of aromatic substitutents. The best generated models were
      validated by leave-one- out technique (LOO-internal validation) and predicting
      the activity of the test (external validation). Further bootstrapping method was
      adopted to assess the robustness of the models. The analysis explores the
      substitutional requirements of the pyridinone moiety of the compounds for
      effective inhibition of HIV-1 RT enzyme.

PMID- 17504194
TI  - 5-fluorouracil derivatives induce differentiation mediated by tubulin and HLA
      class I modulation.
AB  - Neoplastic cells exhibit defects in their ability to differentiate; therefore,
      differentiation therapy represents a viable option to control cancer growth and
      progression. Rhabdomyosarcomas (RMS), a malignant tumor of skeletal muscle, is
      the most common soft tissue sarcoma in children and is characterized by its poor
      response to cytotoxic treatment and significant morbidity. Since modulation of
      alpha-tubulin and human leukocyte antigen (HLA) class I expression has been
      detected during malignant transformation, we analyzed in this study the
      expression pattern of both kinds of proteins after the treatment with 5-FU
      derivatives in the human RMS RD cell line. Cytotoxic assays, scanning and
      transmission electron microscopy, flow cytometry and immunocytochemical analyses
      were used. The compounds analyzed belonged to the following three categories: (a)
      symmetrical bis(5-fluorouracil-1-yl) derivatives with a linker that connects the
      N(1) atoms of both pyrimidine moieties by means of two amide bonds; and (b) an
      ester with the 5-FU base. The whole structure corresponds to the terminal
      fragment of the molecules included in (a) and (c) 5-fluorouracil acyclonucleoside
      like structures. 1-[[3-(3-Chloro-2-hydroxypropoxy)-1-methoxy]propoxy]propyl]-5
      fluorouracil (2), that belongs to the class (a) produced the highest increment of
      tubulin and its intense capillary distribution throughout the cytoplasm. On the
      other hand, N,N-bis[3-(5-fluorouracil-1-yl)-3-methoxypropanoyl]-alpha,alpha;
      diamino-m-xylene (5) and 2 that are included in the class (c) caused the major
      percentage of marked cells by the HLA class I proteins. In short, our results
      showed that the 5-FU derivatives increase HLA class I expression and showed
      greater microtubule stability with an important network of tubulin beams related
      with the degree of differentiation of RD cells. These results could mean a more
      favorable prognosis of the patients affected with these tumors.

PMID- 17504195
TI  - Amide derivatives of 2,3-diarylacrylophenone as estrogen receptor binding
      ligands.
AB  - Substituted amidoalkyl derivatives of 2,3-diarylacrylophenones carrying the amide
      chain on the 3-aryl residue have been prepared by reacting corresponding phenolic
      2,3-diarylacrylophenones with haloalkyl carboxylic acid esters, their hydrolysis
      and subsequent treatment with different alkyl amines. Compounds thus prepared
      were evaluated for their relative binding affinity (RBA) towards estrogen
      receptors (ER), estrogen agonistic and antagonistic activities. Out of eleven
      amide derivatives thus prepared, compounds 7, 13, 15-19, 23, 24 showed
      significant estrogen antagonistic activity. Interestingly the phenolic compound 7
      and the acid ester 18 also exhibited estrogen inhibiting property. Majority of
      the dimethoxy derivatives (R = OCH(3)) showed significantly high estrogenic
      activity. In order to throw light on their SAR, In silico docking of the
      acrylophenone derivatives in the ligand binding site of the ERalpha and their
      comparison with pure steroidal estrogen antagonist ICI-164,384 and the non
      steroidal antiestrogen raloxifene, was carried out. Crystal structure of compound
      6 revealed relative trans-geometry of the 2(B) and 3(C) phenyl rings.

PMID- 17504196
TI  - Effects of behavioral and neurochemical changes on adult excitotoxic lesion of
      the ventral hippocampus.
AB  - BACKGROUND: The postmortem and magnetic resonance imaging studies for
      schizophrenic patients showed neuropathological abnormalities including neuron
      loss and volume reduction in ventral hippocampus (VH), some longitudinal studies
      suggest these changes may be a neurodegenerative process. OBJECTIVES: The present
      study examined the effects of adult bilateral VH lesions on a dopaminergic
      stimulant, methamphetamine (METH)-induced and an N-methyl-(D)-aspartate (NMDA)
      receptor antagonist, dizocilpine (MK-801)-induced behavioral and neurochemical
      changes in rats, in order to evaluate a potential of adult VH lesion animals for
      a model of schizophrenia. METHODS: To study the behavioral effects after
      bilateral VH lesions in adult rats, locomotor activity was measured individually
      by an infra-red sensor. Extracellular concentrations of dopamine in the nucleus
      accumbens (NAc) were measured using in vivo brain microdialysis. RESULTS: The
      bilateral adult VH lesion rats showed a significant enhanced hyperlocomotion in
      response to METH but no changes to MK-801 and phencyclidine; while bilateral
      adult VH lesion enhanced METH-induced increasing dopamine levels in the NAc.
      CONCLUSIONS: The bilateral adult VH lesions enhanced locomotor activity, which
      related to increased dopamine releases in the NAc, induced by a dopaminergic
      stimulant; these findings may suggest a potential of adult VH lesion animal for a
      model reflecting dopamine D2 receptor antagonist-responsive pathophysiology of
      schizophrenia by way of neurodegenerative processes.

PMID- 17504197
TI  - Phenolic Michael reaction acceptors: combined direct and indirect antioxidant
      defenses against electrophiles and oxidants.
AB  - The implications of oxidative stress in the pathogenesis of many chronic human
      diseases has led to the widely accepted view that low molecular weight
      antioxidants could be beneficial and postpone or even prevent these diseases.
      Small molecules of either plant or synthetic origins, which contain Michael
      acceptor functionalities (olefins or acetylenes conjugated to electron
      withdrawing groups) protect against the toxicity of oxidants and electrophiles
      indirectly, i.e., by inducing phase 2 cytoprotective enzymes. Some of these
      molecules, e.g., flavonoid and curcuminoid analogues that have phenolic hydroxyl
      groups in addition to Michael acceptor centers, are also potent direct
      antioxidants, and may therefore be appropriately designated: bifunctional
      antioxidants. By use of spectroscopic methods we identified phenolic chalcone and
      bis(benzylidene)acetone analogues containing one or two Michael acceptor groups,
      respectively, as very efficient scavengers of two different types of radicals:
      (a) the nitrogen-centered 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid)
      (ABTS.+) radical cation, and (b) the oxygen-centered galvinoxyl (phenoxyl)
      radical. The most potent scavengers are those also bearing hydroxyl substituents
      on the aromatic ring(s) at the ortho-position(s). The initial reaction velocities
      are very rapid and concentration-dependent. In the human keratinocyte cell line
      HaCaT, the same compounds coordinately increase the intracellular levels of
      glutathione, glutathione reductase, and thioredoxin reductase. Thus, such
      bifunctional antioxidants could exert synergistic protective effects against
      oxidants and electrophiles which represent the principal biological hazards by:
      (i) scavenging hazardous oxidants directly and immediately; and (ii) inducing the
      phase 2 response to prevent and resolve the consequences of hazardous processes
      that are already in progress, i.e., acting indirectly, but with much more diverse
      and long-lasting effects.

PMID- 17504198
TI  - N-Substituted-2-butyl-5-chloro-3H-imidazole-4-carbaldehyde derivatives as anti
      tumor agents against Ehrlich ascites tumor cells in vivo.
AB  - A new series of N-substituted 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde
      derivatives were synthesized by using the different bioactive heteroaralkyl
      halides with 2-butyl-4-chloro-1H-imidazole-5-carbaldehyde in presence of powdered
      potassium carbonate in DMF medium. These compounds were screened for their
      antitumor activity. Our results show that treatment of imidazole derivatives
      inhibit proliferation EAT cells, decreases the ascites volume and increases the
      survivability of the animals in vivo. These compounds also inhibited the cellular
      proliferation of HUVEC cells in vitro by MTT assay. Further, these compounds
      could induce apoptosis, which is evident by the nuclear condensation of imidazole
      derivatives treated EAT cells in vivo by the cytological analysis. We have
      identified that pyrrolidine substituted imidazole derivative as potent anti-tumor
      compound. These inhibitors could represent as promising candidates for anticancer
      therapies, where the formation of peritoneal malignant ascites is a major cause
      of morbidity and mortality.

PMID- 17504199
TI  - Antimicrobial evaluation of some arylsulfanylpyrazinecarboxylic acid derivatives.
AB  - The radical-ionic coupling of chloropyrazine-2-carboxylic acid derivatives with
      methoxybenzenethiols, carried out in the presence of a heterogeneous copper
      catalyst, provided the series of 6- or 5- or 3-(4-methoxyphenyl)sulfanyl-pyrazine
      2-carboxylic acid derivatives as well as 6- or 5- or 3-(3
      methoxyphenyl)sulfanylpyrazine-2-carboxylic acid derivatives. The prepared
      compounds were evaluated as potential antifungal agents and new
      antituberculotics. Their preliminary in vitro evaluation of antimycobacterial
      activity according to the international program with the Tuberculosis
      Antimicrobial Acquisition and Coordinating Facility (TAACF) is presented. Several
      compounds showed an interesting activity in the preliminary screening with a
      percentage growth inhibition of the virulent Mycobacterium tuberculosis H(37)Rv
      between 50 to 100% at the concentration 6.25 microg/mL. Structure-activity
      relationships among the chemical structure, the physical properties and the
      biological activities of the evaluated compounds are discussed in the article.

PMID- 17504200
TI  - Serum selenium levels in patients with remission and relapse of graves' disease.
AB  - OBJECTIVE: Selenium (Se) in the form of selenocysteine is an essential component
      of the family of the detoxifying enzymes glutathione peroxidase (Gpx) and of the
      iodothyronine selenodeiodinases that catalyze the extrathyroidal production of
      tri-iodothyronine (T(3)). Thus, Se deficiency may seriously influence the
      generation of free radicals, the conversion of thyroxine (T(4)) to T(3) and a
      thyroidal autoimmune process. The aim of this study was to investigate whether
      serum Se levels may influence the outcome of Graves' disease (GD). DESIGN AND
      METHODS: 83 patients (77 women, 6 men) with active GD were retrospectively
      analyzed (mean age 40,0 years). Twenty-four GD patients went into remission and
      were euthyroid during follow-up (median follow-up: 20.1 months), whereas 59
      patients did not go into remission or developed relapse over the following 24
      months. TSH receptor autoantibodies (TRAb) were measured using the second
      generation assay on the basis of human TSH receptor. Se levels were determined at
      the first visit in our outpatient clinic and were correlated with TRAb levels and
      clinical outcome of these patients. RESULTS: Median TRAb levels in the group of
      remission were significantly (p<0.0001) lower than TRAb values in the relapse
      group (2.1 as compared to 8.6 IU/l). By comparing mean serum Se levels in the
      remission and relapse group no significant differences were seen (73.0 vs. 71.7
      microg/l). Detailed analyses of both groups of patients, however, revealed that
      highest serum Se levels (>120 microg/l) were seen in the remission group,
      indicating a positive effect of Se levels on the outcome of GD. In addition, we
      also compared these results with TRAb levels of these patients. We could show
      that TRAb levels and serum Se values were positively correlated in the relapse
      group, whereas a negative correlation of both parameters were seen in the
      remission group, supporting the idea of a positive effect of Se on thyroidal
      autoimmune process. CONCLUSION: Our data indicate that high serum Se levels (>120
      microg/l) may influence the outcome of GD. This is important, as Se
      administration trials in GD, which are under discussion need to be performed with
      Se supplementation at higher dosages than used in autoimmune thyroiditis.

PMID- 17504201
TI  - Peripheral kynurenine metabolism in focal dystonia.
AB  - Substantial evidence indicates that neuroactive kynurenine metabolites play a
      role in the normal physiology of the human brain, and are involved in the
      pathology of neurodegenerative disorders such as Parkinson's disease and
      Huntington's disease. A side-arm product of the pathway, kynurenic acid (KYNA),
      which is synthesized by the irreversible transamination of kynurenine (KYN) by
      kynurenine aminotransferases (KAT I and KAT II), is an excitatory amino acid
      receptor antagonist. In the present study, we measured the level of KYNA and the
      activities of the biosynthetic enzyme isoforms KAT I and KAT II in the plasma and
      in the erythrocytes (RBCs) of patients with cervical dystonia or blepharospasm
      and in age-matched controls. The KAT I and KAT II activities were significantly
      lower in the plasma of the patients in both subgroups. In the RBCs, only the KAT
      I activity was elevated significantly. The KYNA concentration was unchanged in
      both type of patients. These data support the contribution of an altered
      kynurenine metabolism to the pathogenesis of focal dystonia.

PMID- 17504202
TI  - Epigallocatechin-3-gallate and epicatechin-3-gallate from green tea decrease
      plasma non-transferrin bound iron and erythrocyte oxidative stress.
AB  - Beta-thalassemia patients suffer from secondary iron overload caused by increased
      iron absorption and multiple blood transfusions. Excessive iron catalyzes free
      radical formation, causing oxidative tissue damage. Non-transferrin bound iron
      (NTBI) detected in thalassemic plasma is highly toxic and chelatable.
      Desferrioxamine and deferiprone are used to treat the iron overload, but many
      side effects are found. Epigallocatechin gallate (EGCG) and epicatechin gallate
      (ECG) in green tea (GT) show strong antioxidant properties. We separated the EGCG
      and ECG from GT extract using an HPLC, and examined their iron-binding and free
      radical scavenging activities. They bound Fe(3+) rapidly to form a complex with a
      predominant absorption at 560 nm. EGCG and ECG bound chemical Fe(3+) and chelated
      the NTBI in a time- and dose dependent manner. They also decreased oxidative
      stress in iron-treated erythrocytes. In conclusion, EGCG and ECG could be natural
      iron chelators that efficiently decrease the levels of NTBI and free radicals in
      iron overload.

PMID- 17504203
TI  - Effect of alpha-lipoic acid supplementation on trace element levels in serum and
      in postmitotic tissue in aged rats.
AB  - Redistribution of redox-active divalent metal ions (e.g. copper, zinc, and iron)
      in postmitotic tissues of lipoic acid supplemented aging rats has been proposed
      to contribute to metal-catalyzed protein oxidation. DL-alpha lipoic acid (LA)
      (100 mg/kg body wt/day) was administered intraperitoneally to the Sprague-Dawley
      rats for 14 days. Serum copper levels lowered in the aged rats with LA
      supplementation compared to the rats without LA supplementation. On the other
      hand, serum zinc and iron levels increased in the aged rats with LA
      supplementation compared to the rats without LA supplementation. Copper levels of
      the postmitotic tissues were not changed in the aged rats with LA supplementation
      compared to the controls. The heart zinc levels detected in LA supplemented rats
      were significantly lower than controls. Similarly, the iron levels of the heart
      were found to be significantly lower in LA supplemented rats when compared to
      control rats. LA supplementation did not affect brain and muscle iron levels. The
      brain and muscle zinc levels remained the same in both group of rats. Based on
      the findings of our study, we have concluded that LA may exhibit prooxidant
      effect depending on the altered trace element homeostasis. Therefore, our results
      emphasize the importance of monitoring the dose of LA supplementation, duration
      of treatment and its potential harmful effects in the postmitotic tissues of aged
      rats.

PMID- 17504204
TI  - In search of new cures for tuberculosis.
AB  - The last 10 years have seen resurgent industry activity in discovery and
      development of new drugs for the treatment of tuberculosis (TB), a growing
      widespread and devastating (more than 2 million deaths annually) bacterial
      infection that is of increasing concern in developing and developed nations
      alike. This review describes drugs currently being evaluated in the clinic for
      treatment of uncomplicated and drug resistant pulmonary TB, and updates the
      literature on 5 new drugs that entered clinical trials in the last 4 years.

PMID- 17504205
TI  - Experimental models of discovery: prediction and protection must proceed "hand-in
      hand".

PMID- 17504206
TI  - Establishment of cholinergic neuron-like cell lines with differential
      vulnerability to nitrosative stress.
AB  - Cholinergic cell lines were established by fusion of embryonic day 17 wild-type
      neurons from rat basal forebrain (BF) and upper brainstem (BS) with N18tg
      neuroblastoma cells. Isolated clones expressed choline acetyltransferase (ChAT)
      and neuronal nitric oxide synthase (nNOS) activities that were increased upon
      differentiation with retinoic acid. Clones from the BF expressed high levels of
      the tyrosine kinase type A (TrkA) receptor expression and activation of the
      mitogen-activated kinase ERK2 upon treatment with nerve growth factor. Like wild
      type cholinergic populations, the six clones studied were variably resistant to
      nitric oxide (NO) excess from addition of S-nitroso-N-acetyl-D, L-penicillamine
      (SNAP). Of these, the BS2 clone exhibited resistance like in vivo BS cholinergic
      neurons, while the MS10 clone mimicked in vivo BF vulnerability. Apoptosis in
      response to NO excess was preceded by increases in mitochondrial responses
      bax/bcl-2 ratios, but cytochrome C was not released. Mitochondrial levels of
      apoptosis initiating factor (AIF) were either unchanged or increased, and only in
      MS clones was endonuclease G (EndoG) released. Microarray data indicated the
      existence of endoplasmic reticular (ER) stress and caspase-4 and caspase-12 were
      involved in the pathway to DNA fragmentation. The array data also indicated a
      survival role for mdm2, and its blockade rendered vulnerable the brainstem
      survivor clone BS2. Akt and ERK1/2 pathways were activated in response to NO and
      their blockade increased DNA fragmentation. Blockade of GSK-3 alpha/beta, a
      downstream target of Akt, reduced SNAP toxicity and this was more prominent in
      basal forebrain clones. We have identified two cholinergic cell lines useful for
      molecular studies of cholinergic vulnerability. We hypothesize that, in
      cholinergic neurons, control of ER stress signaling may be a major factor in
      differential vulnerability.

PMID- 17504207
TI  - Preconditioning with chronic cerebral hypoperfusion reduces a focal cerebral
      ischemic injury and increases apurinic/apyrimidinic endonuclease/redox factor-1
      and matrix metalloproteinase-2 expression.
AB  - Atherosclerosis may cause severe stenosis of the arteries supplying the brain,
      which induces chronic cerebral hypoperfusion. Although an infarction often occurs
      in the chronically hypoperfused brain area, it has been uncertain whether the
      stroke severity is attenuated or increased when further decrease of blood flow
      occurs. To test the hypothesis that chronic cerebral hypoperfusion is protective
      against the subsequent severe ischemia, we examined the effect of chronic
      cerebral hypoperfusion on brains subjected to acute focal ischemia. Spontaneous
      hypertensive rats were subjected to middle cerebral artery occlusion/reperfusion
      four weeks after bilateral common carotid artery ligation (BCAL) or sham
      operation. The rats with BCAL had smaller infarctions, determined by 2,3,5
      triphenyltetrazolium hydrochloride staining, and less severe neurologic deficits
      than those with sham operation. The number of DNA-damaged cells, examined by the
      in situ nick translation study, was significantly reduced in animals with BCAL.
      Immunoreactivity for apurinic/apyrimidinic endonuclease/redox factor-1, which
      plays a role in cellular defense mechanism, was markedly increased in those with
      BCAL. Indirect evidence of extracellular matrix remodeling, which might be
      associated with adaptive arteriogenesis or angiogenesis, was obtained in the form
      of increased matrix metalloproteinase-2 activity in them. These findings provide
      experimental evidence that chronic cerebral hypoperfusion would be protective
      against subsequent severe ischemic insults.

PMID- 17504208
TI  - Current advances in the treatment of Parkinson's disease with stem cells.
AB  - Stem cell replacement has emerged as the novel therapeutic strategy for
      Parkinson's disease (PD). Control of motor behavior is lost in PD due to the
      selective degeneration of mesencephalic dopamine neurons (DA) in the substantia
      nigra. This progressive loss of DA neurons results in devastating symptoms for
      which there is no cure. Debilitating side effects often result from chronic
      pharmacological treatment, hence current investigations into cell transplantation
      therapy as a substitute and/or adjuvant to other therapeutics. Clinical trials
      with fetal DA tissue have provided evidence that cell transplantation could be a
      viable alternative. Limited availability of fetal tissue, combined with variable
      outcome led to emphasis on other sources of cells, such as stem cells. This
      review focuses on three stem cell sources (embryonic, neural, and adult
      mesenchymal). Also discussed is the molecular differentiation into mature DA
      neurons, the various protocols that have been developed to generate DA neurons
      from various stem cells, and the current state of stem cell therapy for PD.

PMID- 17504209
TI  - The zebrafish model: use in studying cellular mechanisms for a spectrum of
      clinical disease entities.
AB  - Although the zebrafish model provides an important platform for the study of
      developmental biology, recent work with the zebrafish model has extended its
      application to a wide variety of experimental studies relevant to human disease.
      Currently, the zebrafish model is used for the study of human genetic disease,
      caveolin-associated muscle disease, homeostasis, kidney development and disease,
      cancer, cardiovascular disorders, oxidative stress, caloric restriction, insulin
      like pathways, angiogenesis, neurological diseases, liver disease, hemophilia,
      bacterial pathogenesis, apoptosis, osteoporosis, immunological studies, germ cell
      study, Bardet-Biedl syndrome gene (BBS11), Alzheimer's disease, virology studies
      and vaccine development. Here we describe the essential use of the zebrafish
      model that applies to several clinical diseases. With increased understanding of
      the cellular mechanisms responsible for disease, we can use knowledge gained from
      the zebrafish model for the development of therapeutics.

PMID- 17504210
TI  - Role of ischemic blood-brain barrier on amyloid plaques development in
      Alzheimer's disease brain.
AB  - This review demonstrated that ischemic brain injury induces chronic changes in
      blood-brain barrier in the gray and white matter. This insufficiency of blood
      brain barrier may allow entry of uncellular blood components such as different
      fragments of amyloid precursor protein and cellular blood components like
      leukocytes and platelets into the brain parenchyma. These blood components may
      have chronic harmful effects on the ischemic neuronal cells, axons and myelin and
      can intensify and finish the neuropathology in ischemic brain parenchyma.
      Pathological accumulation of different toxic fragments of amyloid precursor
      protein in extracellular space and myelinated axons appears after ischemic blood
      brain barrier injury and seem to be concomitant with, but independent of neuronal
      ischemic cytoplasmic injury. It seems that ischemic blood-brain barrier
      disturbances may play an important, both direct and indirect role in the
      pathogenesis of extra- and intracellular space in gray and white matter lesions
      following ischemic episode. This neuropathology appears to have similar character
      and distribution as in sporadic Alzheimer's disease. This review presented
      chronic micro-blood-brain barrier openings in ischemic gray and white matter
      lesions that probably would act as seeds of future Alzheimer's amyloid plaques.

PMID- 17504211
TI  - Microglial signal transduction as a target of alcohol action in the brain.
AB  - Although alcohol is believed to exert deleterious effects on the nervous system
      in general, its specific effect on the brain's immune system remains poorly
      understood. In particular, the effects of alcohol consumption on the immune and
      inflammatory responses in the central nervous system (CNS) have not been
      extensively investigated. Here, reviewed is the recent progress on how ethanol
      influences the signal transduction pathways of the inflammatory activation of
      brain microglia, which are thought to function as the resident immune defense
      system of the brain. Microglia are the CNS representatives of macrophages, which
      have the ability to clean up cellular debris. Microglia participate in
      neuroinflammation in response to various intrinsic or extrinsic stimuli. It has
      been recently suggested that microglial signal transduction is one of the main
      targets of ethanol action in the brain: ethanol exposure selectively modulates
      the intracellular signal transductions of microglia, rather than globally
      inhibiting signaling pathways in a nonspecific manner. Deregulation by ethanol of
      the inflammatory activation signaling of microglia may contribute to the
      derangement of CNS immune and inflammatory responses.

PMID- 17504212
TI  - The role of neurotrophins in axonal growth, guidance, and regeneration.
AB  - Neurotrophins are proteins that regulate neuronal survival, axonal growth,
      synaptic plasticity and neurotransmission. They are members of the neurotrophic
      factors family and include factors such as the nerve growth factor (NGF), the
      brain derived neurotrophic factor (BDNF), the neurotrophin-3 (NT-3), and the
      neurotrophin-4/5 (NT-4/5). These molecules bind to two types of receptors: i)
      tyrosine kinase receptors (TrkA, TrkB, TrkC) and ii) a common neurotrophin
      receptor (p75NTR). The two receptor types can either suppress or enhance each
      other's actions. Neurotrophins have a multifunctional role both in the central
      and peripheral nervous system. They have been suggested as axonal guidance
      molecules during the growth and regeneration of nerves. It has also been proven
      that they stimulate axonal growth by mediating the polymerization and
      accumulation of F-actin in growth cones and axon shafts. Neurotrophins, as other
      neurotrophic factors, have been shown that they reduce neuronal injury by
      exposure to excitotoxins, glucose deprivation, or ischemia. Furthermore, the
      nerve regeneration promoting effect of these growth factors is well documented
      for many different models of central or peripheral nervous system injury. Several
      studies have shown that exogenous administration of these factors has protective
      properties for injured neurons and stimulates axonal regeneration. Based on these
      properties, these molecules may be used as therapeutic agents for treating
      degenerative diseases and traumatic injuries of both the central and peripheral
      nervous system.

PMID- 17504213
TI  - Interferon: cellular executioner or white knight?
AB  - Interferons (IFNs) are a family of pleiotropic cytokines that typically exhibit
      antiviral, antiproliferative, antitumor, and immunomodulatory properties. While
      their complex mechanisms of action remain unclear, IFNs are used clinically in
      the treatment of viral infections, such as hepatitis B and hepatitis C, and
      remain the primary treatment for a limited number of malignancies, such as
      melanoma, hairy cell leukemia, and non-Hodgkin's lymphoma and in autoimmune
      diseases such as multiple sclerosis. IFNs not only regulate somatic cell growth
      and division but also influence cell survival through the modulation of
      apoptosis. Paradoxically, IFNs are described to be both pro- and anti-apoptotic
      in nature. The biological effects of IFNs are primarily mediated via activation
      of the JAK/STAT pathway, formation of the ISGF3 and STAT1:STAT1 protein
      complexes, and the subsequent induction of IFN-stimulated genes. However, the
      activation of JAK/STAT-independent signal transduction pathways also contribute
      to IFN-mediated responses. To further demonstrate the complexity of the
      downstream events following stimulation, oligonucleotide microarray studies have
      shown that in excess of 300 genes are induced following treatment with IFN, some
      of which are crucial to the induction of apoptosis and cell growth control. In
      this review we describe the recent advances made in elucidating the various
      signaling pathways that are activated by IFNs and how these diverse signals
      contribute to the regulation of cell growth and apoptosis and inhibition of viral
      replication. Furthermore, we highlight the role of specific signaling molecules
      and the function(s) of particular IFN-stimulated genes that have been implicated
      in determining cell fate in response to IFN, as well as the clinical experience
      of IFN immunotherapy.

PMID- 17504214
TI  - Pyridoxal 5'-phosphate enzymes as targets for therapeutic agents.
AB  - The vitamin B(6)-derived pyridoxal 5'-phosphate (PLP) is the cofactor of enzymes
      catalyzing a large variety of chemical reactions mainly involved in amino acid
      metabolism. These enzymes have been divided in five families and fold types on
      the basis of evolutionary relationships and protein structural organization.
      Almost 1.5% of all genes in prokaryotes code for PLP-dependent enzymes, whereas
      the percentage is substantially lower in eukaryotes. Although about 4% of enzyme
      catalyzed reactions catalogued by the Enzyme Commission are PLP-dependent, only a
      few enzymes are targets of approved drugs and about twenty are recognised as
      potential targets for drugs or herbicides. PLP-dependent enzymes for which there
      are already commercially available drugs are DOPA decarboxylase (involved in the
      Parkinson disease), GABA aminotransferase (epilepsy), serine
      hydroxymethyltransferase (tumors and malaria), ornithine decarboxylase (African
      sleeping sickness and, potentially, tumors), alanine racemase (antibacterial
      agents), and human cytosolic branched-chain aminotransferase (pathological states
      associated to the GABA/glutamate equilibrium concentrations). Within each family
      or metabolic pathway, the enzymes for which drugs have been already approved for
      clinical use are discussed first, reporting the enzyme structure, the catalytic
      mechanism, the mechanism of enzyme inactivation or modulation by substrate-like
      or transition state-like drugs, and on-going research for increasing specificity
      and decreasing side-effects. Then, PLP-dependent enzymes that have been recently
      characterized and proposed as drug targets are reported. Finally, the relevance
      of recent genomic analysis of PLP-dependent enzymes for the selection of drug
      targets is discussed.

PMID- 17504215
TI  - Genetic polymorphisms in the chemokine and chemokine receptors: impact on
      clinical course and therapy of the human immunodeficiency virus type 1 infection
      (HIV-1).
AB  - The natural history and pathogenic processes of infection by the human
      immunodeficiency virus type 1 (HIV-1) are complex, variable, and dependent upon a
      multitude of viral and host factors and their interactions. The CCR5-Delta32
      allele remains the most important genetic factor known to be associated with host
      resistance to the HIV-1 infection. However, other mutations in the CCR5, CCR2,
      CX(3)CR1, CXCL12 (SDF1), and CCL5 (RANTES) genes have been identified and
      associated with host resistance and/or susceptibility to HIV-1 infection and
      disease progression. Some studies have also suggested that chemokine receptor
      gene polymorphisms may affect response to potent antiretroviral therapy. This
      article reviews the polymorphisms already described in the mutant chemokine
      receptors or ligands and their impact on the host susceptibility to HIV-1
      infection and on the clinical course of the disease, as well as the development
      of new anti-HIV therapies that takes into account these potential targets in the
      host. These genetic polymorphisms could be used as genetic markers to detect
      individuals at higher risk of developing either a faster disease progression or
      therapeutic failure. Once these individuals are identified, therapeutic
      strategies based on either different, more aggressive drugs or combinations of
      drugs can be used, either alone or in combination with shorter intervals for
      therapeutic monitoring. Pharmacogenetics is very likely to underlie future
      therapies for HIV-1 infection, and current patients with multi-resistance to the
      existing antiretroviral agents could also benefit from this approach. These
      developments also underscore the importance of continuing the investigation of
      new therapies targeted to the host in order to inhibit the HIV-1 entry into the
      host cells.

PMID- 17504216
TI  - Inhaled insulin and the lung.
AB  - Pulmonary delivery of insulin is more than a promise in the treatment of diabetes
      mellitus. Inhaled insulin seems at least as efficacious as the conventional
      regimen of subcutaneous insulin and/or oral glucose-lowering agents in both type
      1 and type 2 diabetes mellitus. Improved metabolic control and the use of a non
      invasive route of administration represent the main benefits of this new
      treatment. Several physico-chemical factors could reduce the bioavailability of
      inhaled insulin. Indeed, both deep-lung deposition and adsorption of insulin
      variously depend on the type of propellants used, speed of air flow, particle
      size and velocity, drug deposition into the throat and larger bronchial tree.
      These factors, in turn, depend on the pulmonary delivery systems used and on
      respiratory mechanics and flows. Furthermore, the pharmacokinetics of inhaled
      insulin is affected by smoke, which increases its absorption, and by lung
      diseases, which decrease the available alveolar-capillary surface. Selected
      abnormalities of respiratory function complicate both type 1 and type 2 diabetes
      mellitus and a mild depression of carbon monoxide lung transfer after a 6-month
      period of treatment with inhaled insulin has been reported. Finally, results from
      some longitudinal studies suggest that diabetes might speed up the age-related
      decline of lung volumes and probably alter the pharmacokinetics of inhaled
      insulin, particularly in the elderly. Clarifying these issues is mandatory in
      order to define the indications and safety of inhaled insulin.

PMID- 17504217
TI  - A review on synthetic and natural steroid dimers: 1997-2006.
AB  - Since the publication of the review by Li and Dias in 1997, which covered almost
      all steroid dimers known to us until the early part of 1997, there have been
      significant amounts of work carried out on steroid dimers, and another review on
      this topic has long been overdue. Thus, this review presents a comprehensive
      review of literature published over the last decade on various aspects of steroid
      dimers, including synthesis and applications. Steroid dimers that were published
      before 1997 but were not covered within the previous review have also been
      included.

PMID- 17504218
TI  - Angiomodulatory and neurological effects of ginsenosides.
AB  - Panax ginseng C.A. Meyer, one of the most popular and valued herbs, has been used
      extensively in traditional Chinese medicine for thousands of years. More than
      thirty ginsenosides, the pharmacologically active ingredients in ginseng, have
      been identified with various sugar moieties attached at the C-3, C-6 and C-20
      positions of the steroidal skeleton. We herein review the current literature on
      the pharmacological effects of ginsenosides on the modulation of angiogenesis,
      dysregulations of which contribute towards many pathological conditions.
      Regarding the adaptogenic property of ginseng, the effects of ginsenosides on
      central nervous system are also discussed. Recent researches have pointed to the
      steroid hormone receptors as the target molecules to elicit the diverse cellular
      and physiological activities of ginseng. We believe that understanding the
      interaction between ginsenosides and various steroid hormone receptors may
      provide clues to unravel the secret of ginseng.

PMID- 17504219
TI  - Expression and function of cytochrome p450 in brain drug metabolism.
AB  - Cytochrome P450 (CYP, P450) is the collective term for a superfamily of heme
      containing membrane proteins responsible for the metabolism of approximately 70 -
      80 % of clinically used drugs. Besides the liver and other peripheral organs,
      P450 isoforms are expressed in glial cells and neurons of the brain. To enlighten
      their function and significance is a topic of high interest, as most of the
      neuroactive drugs used in therapy today are not only substrates, but also
      inducers of brain P450s with far reaching consequences. First of all, brain P450s
      are regulated differentially from those in liver. The availability of the
      prosthetic heme group appears to be essential for correct membrane insertion and
      enzymatic functionality of brain P450s. Furthermore, although not contributing to
      body's overall drug metabolism, brain P450s fulfil particular functions within
      specific cell types of the brain. In astrocytes of brain's border lines P450
      isoforms are expressed at very high level. They form a metabolic barrier
      regulating drugs' influx, modulate blood-flow regulation, and act as signalling
      enzymes in inflammation. In neurons, however, P450s apparently have different
      function. In specified brain regions such as hypothalamus, hippocampus and
      striatum they provide signalling molecules like steroids and fatty acids
      necessary for neuronal outgrowth and maintenance. Induction of these P450s by
      neuroactive drugs can alter steroid hormone signalling directly in drug target
      cells, which may cause clinically relevant side effects like reproductive
      disorders and sexual or mental dysfunction. The understanding of brain P450
      function appears to be of major interest in long-term drug mediated therapy of
      neurological diseases.

PMID- 17504220
TI  - CYP-mediated clozapine interactions: how predictable are they?
AB  - Despite the introduction of newer drugs, the atypical antipsychotic clozapine
      remains the most effective drug in psychotic patients who are resistant to
      treatment with conventional agents. Optimal therapeutic responses to clozapine
      have been reported with serum concentrations between 350 microg/L and 1000
      microg/L. Clozapine is frequently combined with other drugs to enhance efficacy
      and reduce adverse reactions but pharmacokinetic interactions can have a
      significant impact on drug response. The majority of the interactions with
      clozapine are reported to be mediated by cytochrome P450 (CYP) enzymes. CYP1A2
      has a major role in the oxidative metabolism of clozapine, with a minor
      contribution from CYP3A4, and possibly CYP2D6, CYP2C9 and CYP2C19. Interactions
      mediated by potent CYP1A2 inhibitors (such as fluvoxamine) or inducers (like
      cigarette smoke) appear to be consistent, predictable and usually clinically
      significant. There are many case reports of interactions between clozapine and
      weak CYP1A2 inhibitors or inducers which are also potent inhibitors or inducers
      of CYP3A4 or CYP2D6. Researchers often explain these observations on the basis of
      the CYP1A2 involvement. In addition, there are case reports of clinically
      significant interactions between clozapine and drugs that are not substrates,
      inhibitors or inducers of CYP1A2. These interactions are difficult to predict and
      may not be consistent, as reflected by the conflicting literature reports.
      Further research to elucidate individual differences in clozapine metabolism,
      with the potential to detect the dominant roles of CYPs other than CYP1A2, may
      assist us in predicting these interactions.

PMID- 17504221
TI  - The non-ABC drug transporter RLIP76 (RALBP-1) plays a major role in the
      mechanisms of drug resistance.
AB  - RLIP76 or Ral binding protein (RalBP-1) was initially cloned as a Ral-effector
      that was proposed as a link between Ral and Ras pathways. This protein is encoded
      in humans on chromosome 18p11.3 by a gene with 11 exons and 9 introns and is
      found ubiquitously from drosophila to humans. RLIP76 displays inhibitory GTPase
      activity toward Rho/Rac class G-protein cdc42 which is involved in regulation of
      cytoskeletal organization, lamellipodia, cell migration and apoptosis via Ras. We
      have recently shown that RLIP76 is also a multispecific transporter of
      chemotherapeutic agents and glutathione conjugates (GS-E). In human cells RLIP76
      accounts for more than two third of the transport activity for GS-E and drugs as
      opposed to the ABC-transporters including MRP1, which account for less than one
      third of this activity. Evidence is mounting that RLIP76 is a stress-responsive
      multi-specific, non-ABC transporter which represents an entirely novel link
      between stress-inducible G-protein signaling, receptor tyrosine-kinase signaling,
      endocytosis, heat-shock and stress defense pathways, and transport mediated drug
      resistance. The expression of RLIP76 is significantly greater in human cancer
      cells of diverse origin as compared to the non-malignant cells. Inhibition of
      RLIP76, using antibodies towards a cell surface epitope, or depletion of RLIP76
      using either siRNA or anti-sense phosphorothioate oligonucleotides preferentially
      causes apoptosis in malignant cells. Administration of RLIP76 antibodies, siRNA,
      or anti-sense oligonucleotides to mice bearing syngeneic B16 mouse melanoma
      tumors causes rapid and complete regression of tumors. Studies summarized in this
      review strongly suggest that RLIP76 is a logical target for clinical intervention
      of not only multi-drug resistance but also for diseases resulting from oxidative
      stress.

PMID- 17504222
TI  - Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a major
      active ingredient in the root of Salvia miltiorrhiza Bunge.
AB  - The extracts from the roots of Salvia miltiorrhiza Bunge (Danshen) are widely and
      traditionally used in the treatment of angina pectoris, acute myocardial infarct,
      hyperlipidemia and stroke in China and other Asian countries. In this study, we
      have investigated the role of P-glycoprotein (P-gp) in the intestinal absorption
      of tanshinone IIA (TSA), a major active constituent of Danshen, using several in
      vitro and in vivo models. The oral bioavailability of TSA was about 2.9-3.4% in
      rats, with non-linear pharmacokinetics when its dosage increased. In a single
      pass rat intestinal perfusion model, the permeability coefficients (P(app)) based
      on TSA disappearance from the luminal perfusates (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 P(blood), but not P(lumen), was significantly increased when co
      perfused with verapamil, or quinidine (both P-gp inhibitors). The uptake and
      efflux of TSA in confluent Caco-2 cells were significantly altered in the
      presence of verapamil, quinidine, MK-571, or probenecid. The transport of TSA
      across Caco-2 monolayers was pH-, temperature- and ATP-dependent. Furthermore,
      the transport from the apical (AP) to basolateral (BL) side of the Caco-2
      monolayers was 3.3- to 8.5-fold lower than that from the BL to AP side, but such
      a polarized transport was attenuated by co-incubated verapamil or quinidine. A
      polarized transport was also observed in the control MDCKII cells and more
      apparent in MDR1-MDCKII monolayers, with the P(app) values of TSA in the BL-AP
      direction being 7- to 9-fold higher in MDR1-MDCKII monolayers than those in the
      control MDCKII cells. Moreover, TSA significantly inhibited P-gp-mediated
      transport of digoxin in P-gp-overexpressing membrane vesicles with an IC(50) of
      2.6 microM, but stimulated vanadate-sensitive P-gp ATPase activity with estimated
      K(m) and V(max) values of 10.70 +/- 0.69 microM and 67.65 +/- 1.31 nmol/min/mg
      protein, respectively. TSA was extensively metabolized to tanshinone IIB (TSB),
      and two other oxidative metabolites in rat liver microsomes, but the formation
      rate of TSB in rat intestinal microsomes was only about 1/10 of that in liver
      microsomes. These findings indicate that TSA is a substrate and reversing agent
      for P-gp; and P-gp-mediated efflux of TSA into the gut lumen and the first-pass
      metabolism contribute to the low oral bioavailability. Further studies are needed
      to explore the role of other drug transporters and first-pass metabolism in the
      low bioavailability of TSA.

PMID- 17504223
TI  - Evaluation of drug-transporter interactions using in vitro and in vivo models.
AB  - Drug transporters, including efflux transporters (the ATP binding cassette (ABC)
      proteins) and uptake transporters (the solute carrier proteins (SLC)), have an
      important impact on drug disposition, efficacy, drug-drug interactions and
      toxicity. Identification of the interactions of chemical scaffolds with
      transporters at the early stages of drug development can assist in the
      optimization and selection of new drug candidates. In this review, we discuss
      current in vitro and in vivo models used to investigate the interactions between
      drugs and transporters such as P-gp, MRP, BCRP, BSEP, OAT, OATP, OCT, NTCP,
      PEPT1/2 and NT. In vitro models including cell-based, cell-free, and yeast
      systems as well as in vivo models such as genetic knockout, gene deficient and
      chemical knockout animals are discussed and compared. The applications,
      throughput, advantages and limitations of each model are also addressed in this
      review.

PMID- 17504224
TI  - Transport of cryptotanshinone, a major active triterpenoid in Salvia miltiorrhiza
      Bunge widely used in the treatment of stroke and Alzheimer's disease, across the
      blood-brain barrier.
AB  - Cryptotanshinone (CTS), a major constituent from the roots of Salvia miltiorrhiza
      (Danshen), is widely used in the treatment of coronary heart disease, stroke and
      less commonly Alzheimer's disease. Our recent study indicates that CTS is a
      substrate for P-glycoprotein (PgP/MDR1/ABCB1). This study has investigated the
      nature of the brain distribution of CTS across the brain-blood barrier (BBB)
      using several in vitro and in vivo rodent models. A polarized transport of CTS
      was found in rat primary microvascular endothelial cell (RBMVEC) monolayers, with
      facilitated efflux from the abluminal side to luminal side. Addition of a PgP
      (e.g. verapamil and quinidine) or multi-drug resistance protein 1/2 (MRP1/2)
      inhibitor (e.g. probenecid and MK-571) in both luminal and abluminal sides
      attenuated the polarized transport. In a bilateral in situ brain perfusion model,
      the uptake of CTS into the cerebrum increased from 0.52 +/- 0.1% at 1 min to
      11.13 +/- 2.36 ml/100 g tissue at 30 min and was significantly greater than that
      of sucrose. Co-perfusion of a PgP/MDR1 (e.g. verapamil) or MRP1/2 inhibitor (e.g.
      probenecid) significantly increased the brain distribution of CTS by 35.1-163.6%.
      The brain levels of CTS were only about 21% of those in plasma, and were
      significantly increased when coadministered with verapamil or probenecid in rats.
      The brain levels of CTS in rats subjected to middle cerebral artery occlusion and
      rats treated with quinolinic acid (a neurotoxin) were about 2- to 2.5-fold higher
      than the control rats. Moreover, the brain levels in mdr1a(-/-) and mrp1(-/-)
      mice were 10.9- and 1.5-fold higher than those in the wild-type mice,
      respectively. Taken collectively, these findings indicate that PgP and Mrp1 limit
      the brain penetration of CTS in rodents, suggesting a possible role of PgP and
      MRP1 in limiting the brain penetration of CTS in patients and causing drug
      resistance to Danshen therapy and interactions with conventional drugs that are
      substrates of PgP and MRP1. Further studies are needed to explore the role of
      other drug transporters in restricting the brain penetration of CTS and the
      clinical relevance.

PMID- 17504225
TI  - A pharmacokinetic interaction between clarithromycin and sirolimus in kidney
      transplant recipient.
AB  - Bacterial infection is a frequent event in renal transplant recipients and often
      requires the use of antimicrobial agents. In this paper it is reported an
      evidence of pharmacokinetic interaction between clarithromycin and sirolimus in a
      kidney transplanted woman, suffering from pulmonary infection sustained by a
      bacterial pathogen, in particular Hemophilus Influenzae. In the present case
      report, the concomitant administration of clarithromycin and sirolimus determined
      impressive increase of sirolimus trough blood concentrations from 6.2 up to 54
      ng/mL and this increase was associated with an acute impairment of renal
      function, almost completely reversed upon both drugs discontinuation. This drug
      drug interaction is due to a likely inhibition of activity of both cytochrome
      P450 3A4 and P-glycoprotein. Although this interaction could be predicted, it
      represents the first reported clinical evidence.

PMID- 17504226
TI  - Histone deacetylase inhibitors: molecular and biological activity as a premise to
      clinical application.
AB  - Epigenetic modifications are reversible chromatin rearrangements that in normal
      cells modulate gene expression, without changing DNA sequence. Alterations of
      this equilibrium, mainly affecting the two interdependent mechanisms of DNA
      methylation and histone acetylation, are frequently involved in the genesis of
      cancer. The histone code, regulating gene expression, is constituted by the
      combination of different acetylated lysine residues of histones. In neoplastic
      cells, the abundance of deacetylated histones is usually associated with DNA
      hypermethylation and gene silencing. Several compounds, known to have in vitro
      antineoplastic activity, have been eventually shown to act as histone deacetylase
      inhibitors. Thus, HDAC inhibitors have been successfully introduced in clinical
      trials as antitumour agents. They are classified according to their chemical
      structures and are endowed with different specificity and affinity for the HDACs
      of classes 1, 2, 4. Among HDAC inhibitors, the most potent are the hydroxamic
      acid derivatives, like SAHA, which has been recently approved for therapy of
      cutaneous T-cell lymphomas. Other classes of HDAC inhibitors are short chain
      fatty acids (SCFA), benzamides, epoxyketone and non-epoxyketone containing cyclic
      tetrapeptides, and hybrid molecules. SCFA, although widely used (especially
      valproic acid) and clinically efficacious, have weak HDAC inhibition constants.
      Benzamides, like MS-275, and cyclic peptides, like depsipeptide, have been
      studied in numerous clinical trials and demonstrated low toxicity and activity in
      solid and haematological neoplasms. HDAC inhibitors are also potent radiation
      sensitizers. Their future in oncology may thus be based on their activity as
      single agents and on their synergy with the hypomethylating drugs and with chemo-
      and radiotherapeutics.

PMID- 17504229
TI  - Demystifying the ACE polymorphism: from genetics to biology.
AB  - The angiotensin converting enzyme (ACE) I/D polymorphism has been one of the most
      studied genetic systems. It comprises hundreds of reports and a myriad of disease
      associations, including cardiovascular, metabolic, immune, cancer, aging,
      neurodegenerative and psychiatric diseases. Despite the wealth of information on
      the ACE polymorphism and the well-known functions of ACE, several questions
      arise. Why does the ACE polymorphism associate with so many diseases? What is its
      function? In this review, we summarize the current information on the ACE
      polymorphism and explain its function in the context of cell survival. We also
      provide a model to understand its role in biology and disease at the organism and
      population levels.

PMID- 17504227
TI  - Synergistic cytotoxic activity of recombinant TRAIL plus the non-genotoxic
      activator of the p53 pathway nutlin-3 in acute myeloid leukemia cells.
AB  - To potentiate the response of acute myeloid leukemia (AML) to TRAIL cytotoxicity,
      we have adopted a strategy of combining nutlin-3, a potent non-genotoxic
      activator of the p53 pathway, with recombinant TRAIL. The rationale for using
      such a combination was that deletions and/or mutations of the p53 gene occur in
      only 5-10% of AML and that TRAIL and nutlin-3 activate the extrinsic and
      intrinsic pathways of apoptosis, respectively. TRAIL induced a rapid increase of
      apoptosis when added to OCI M4-type and MOLM M5-type AML cells, carrying a wild
      type p53, as well as to NB4 M3-type AML, carrying a mutated p53. On the other
      hand, the small molecule activator of the p53 pathway nutlin-3 induced p53
      accumulation, cell cycle arrest and a slow progressive increase of apoptosis in
      OCI and MOLM but not in NB4. Of note, nutlin-3 up-regulated the surface
      expression of TRAIL-R2 and synergized with TRAIL in inducing apoptosis in OCI and
      MOLM as well as in primary M4-type and M5-type AML blasts, but not in NB4 cells.
      Moreover, while nutlin-3 up-regulated the expression of cyclin dependent kinase
      inhibitor p21, a p53-target gene mediating cell cycle block and showing anti
      apoptotic activity, the simultaneous addition of TRAIL plus nutlin-3 induced the
      caspase-dependent cleavage of p21. The relevance of p21 down-regulation for
      sensitizing AML cells to apoptosis was underscored in knocking-down experiments
      with small interfering RNAs. Our data suggest that the combined treatment of
      nutlin-3 plus TRAIL might offer a novel therapeutic strategy for AML.

PMID- 17504230
TI  - Pharmacological, immunological, and gene targeting of the renin-angiotensin
      system for treatment of cardiovascular disease.
AB  - Effective blood pressure control with a large arsenal of conventional
      antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium
      channel blockers, significantly reduce the morbidity and mortality associated
      with cardiovascular disease. However, blood pressure control with these drugs
      does not reduce cardiovascular disease risks to the levels in normotensive
      persons. Only two drug classes that inhibit or antagonize portions of the renin
      angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and
      angiotensin receptor type-1 (AT(1) receptor) blockers, have protective and
      beneficial effects unrelated to the degree of blood pressure reduction. These
      drugs may prevent the blood pressure related functional and structural
      abnormalities of the cardiovascular system and reduce the end organ-damage. The
      first part of this review presents the components of the RAS, biological actions
      of angiotensin peptides, and the functions of the enzymes that generate and
      metabolize angiotensins, including the likely effect of manipulating them.
      Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The
      second part of this review presents the rationale for targeting the RAS, based on
      clinical studies of the ACE inhibitors and AT(1) receptor blockers. Finally, we
      present the investigational agents acting on the RAS that have a potential for
      clinical usage, and give the perspective of pharmacological, immunological and
      gene targeting of the RAS for treatment of cardiovascular disease.

PMID- 17504231
TI  - The renin angiotensin system in the regulation of angiogenesis.
AB  - Decades of experimentation on angiotensin and bradykinin have focused on
      macrovascular systemic effects. However, angiotensin II and bradykinin are both
      angiogenic agents, highlighting their ability to also effect the microvascular
      circulation. Not surprisingly, inhibition of angiotensin converting enzyme, which
      inhibits angiotensin II synthesis and bradykinin degradation, would have
      different impacts on angiogenesis in vivo dependent upon what factors were
      present in the system. Several pathological states in which angiogenesis is
      important, including peripheral ischemia, stroke, retinopathy, and cancer are
      examined in this review with respect to activity of angiotensin II and bradykinin
      and the impact of angiotensin converting enzyme inhibition. Although
      generalizations are not without legitimate criticism, one can think about
      peripheral ischemia and stroke as being more dependent upon bradykinin signaling
      and retinopathy and cancer as more dependent upon angiotensin II signaling to
      drive angiogenesis. Many exceptions are found that are specific to individual
      animal model systems. Furthermore, cancer systems that have been examined at any
      depth are few. However, published data on in vitro cultures and animal models
      present interesting predictions about how the renin angiotensin and bradykinin
      systems may function in humans. Since angiotensin converting enzyme inhibitors
      have been widely utilized pharmaceuticals for many years, we are now accumulating
      epidemiological data that test our predictions. The importance of understanding
      which agent, angiotensin and/or bradykinin, appears to be the more important
      regulator of angiogenesis in a given pathology will become increasing evident as
      more specific angiotensin II and bradykinin receptor blocking drugs make their
      way into clinical use.

PMID- 17504232
TI  - The two fACEs of the tissue renin-angiotensin systems: implication in
      cardiovascular diseases.
AB  - The implication of the renin-angiotensin system (RAS) in the regulation of the
      cardiovascular system has been well known for many years. Accordingly, many
      pharmaceutical inhibitors have been developed to treat several pathologies, like
      hypertension and heart failure, and angiotensin converting enzyme (ACE) became
      one of the major target in the treatment of these cardiovascular diseases. In the
      last decade however, it has become apparent that the classical view of the RAS
      was not quite accurate. For instance, ACE has been shown to work not only by
      generating angiotensin-II but also by interacting with receptors outside the
      renin-angiotensin system. Moreover, it has been shown that many local RAS are
      present in different tissues, such as the heart, brain, kidney and vasculature.
      However, in the past, it was impossible to determine the role of these local
      systems as they were pharmacologically indistinguishable from the systemic RAS.
      Hence, in recent years, the development of transgenic animals has allowed us to
      determine that these local systems are implicated in the roles that had been
      originally attributed exclusively to the systemic action of the RAS. However,
      with almost 30% of the medicated hypertensive patients harboring an uncontrolled
      blood pressure, a need for new drugs and new targets appears necessary. With the
      new century came the discovery of a new homolog of ACE, called ACE2, and early
      studies suggest that it may play a pivotal role in the RAS by controlling the
      balance between the vasoconstrictor effects of angiotensin-II and the
      vasodilatory properties of the angiotensin(1-7) peptide. Like ACE, ACE2 appears
      to hydrolyze peptides not related with the RAS and the enzyme has also been
      identified as a receptor for the severe acute respiratory syndrome (SARS)
      coronavirus. Although the tissue localization of ACE2 was originally though to be
      very restricted, new studies have emerged showing a more widespread distribution.
      Therefore, the whole dynamics of the RAS has to be re-evaluated in light of this
      new information. In this review, we will compare the structures, distributions
      and properties of ACE and its new homologue in the context of cardiovascular
      function, focusing on the autocrine/paracrine cardiac and brain renin-angiotensin
      systems and we will present recent data from the literature and our laboratory
      offering a new perspective on this potential target for the treatment of
      cardiovascular diseases.

PMID- 17504233
TI  - Angiotensin-TGF-beta 1 crosstalk in human idiopathic pulmonary fibrosis:
      autocrine mechanisms in myofibroblasts and macrophages.
AB  - Angiotensin II (ANGII) has been identified as a proapoptotic and profibrotic
      factor in experimental lung fibrosis models, and patients with the ID/DD
      polymorphism of ANG converting enzyme (ACE), which confers higher levels of ACE,
      are predisposed to lung fibrosis (Hum. Pathol. 32:521-528, 2001). Previous work
      from this laboratory has shown that human lung myofibroblasts isolated from
      patients with Idiopathic Pulmonary Fibrosis (IPF) synthesize the ANGII precursor
      angiotensinogen (AGT) constitutively. In attempts to understand the mechanisms
      and consequences of constitutive AGT synthesis by myofibroblasts, we studied
      myofibroblast-rich primary cultures of lung fibroblasts from patients with IPF
      (HIPF isolates), primary fibroblasts from normal human lung (NLFs), the IMR90 and
      WI38 human lung fibroblasts cell lines, and paraffin sections of lung biopsies
      from patients with IPF. Compared to the normal NLF isolates, HIPF primary
      fibroblast isolates constitutively synthesized more AGT and TGF-beta1 mRNA, and
      released more AGT protein, ANGII and active TGF-beta1 protein into serum-free
      conditioned media (both p<0.01). Incubation of HIPF fibrotic isolates with the
      ANGII receptor antagonist saralasin reduced both TGF-beta1 mRNA and active
      protein, suggesting that the constitutive expression of AGT drives the higher
      expression of TGF-beta1 by the HIPF cells. Consistent with this premise,
      treatment of either the primary NLFs or the WI38 cell line with 10(-7) M ANGII
      increased both TGF-beta1 mRNA and soluble active TGF-beta1 protein. Moreover,
      induction of the myofibroblast transition in the IMR90 cell line with 2 ng/ml TGF
      beta1 increased steady state AGT mRNA levels by realtime PCR (8-fold, p<0.01) and
      induced expression of an AGT promoter-luciferase reporter construct by over 10
      fold (p<0.001). Antisense oligonucleotides against TGF-beta1 mRNA or TGF-beta
      neutralizing antibodies, when applied to the fibrotic HIPF cells in serum-free
      medium, significantly reduced AGT expression. In lung sections from IPF patient
      biopsies, immunoreactive AGT/ANGI proteins were detected in myofibroblasts,
      epithelial cells and presumptive alveolar macrophages. Together, these data
      support the existence of an angiotensin/TGF-beta1 "autocrine loop" in human lung
      myofibroblasts and also suggest ANG peptide expression by epithelia and
      macrophages in the IPF lung. These findings may explain the ability of ACE
      inhibitors and ANG receptor antagonists to block experimental lung fibrosis in
      animals, and support the need for evaluation of these agents for potential
      treatment of human IPF. This manuscript discusses the data described above and
      their implications regarding IPF pathogenesis.

PMID- 17504234
TI  - Attenuation of bleomycin-induced pulmonary fibrosis by intratracheal
      administration of antisense oligonucleotides against angiotensinogen mRNA.
AB  - Apoptosis of alveolar epithelial cells (AECs) is believed to be critical for the
      development of bleomycin (BLEO)-induced pulmonary fibrosis. Previous studies
      showed that apoptosis of alveolar epithelial cells in response to BLEO could be
      abrogated by antisense oligonucleotides against angiotensinogen (AGT) mRNA and
      requires angiotensin II (ANG II) synthesis de novo [17]. In this study we
      hypothesized that blockade of local pulmonary ANG II synthesis by intratracheal
      (I.T.) administration of antisense oligonucleotides against AGT mRNA might
      attenuate BLEO-induced apoptosis of AECs and prevent pulmonary fibrosis. In a
      BLEO-induced rat model of lung fibrosis, endogenous lung AGT was upregulated in
      vivo as early as 3 hours after BLEO instillation, as detected by RT-PCR, in situ
      hybridization and immunohistochemistry. AGT mRNA and angiotensin peptides were
      localized in type II alveolar epithelial cells and also colocalized with alpha
      smooth muscle actin (alpha-SMA), a marker of myofibroblasts. Tagged antisense
      administered I.T. was specifically accumulated by the lung relative to liver and
      kidney, and localized primarily in the epithelium of airways and cells within
      alveolar walls. The intratracheal AGT antisense reduced BLEO-induced pulmonary
      fibrosis measured by lung hydroxyproline assay, decreased lung AGT and active
      caspase-3 proteins, and reduced the number of apoptotic epithelial cells but had
      no effect on the serum ANG II concentration. These data are consistent with the
      hypothesis that lung-derived AGT and local pulmonary ANG II are required for BLEO
      induced pulmonary fibrosis, and suggest the possibility of antisense-based
      manipulation of the local angiotensin system as a potential treatment of fibrotic
      lung diseases.

PMID- 17504235
TI  - The neurobiological bases for the pharmacotherapy of nicotine addiction.
AB  - Nicotine, the major psychoactive agent present in tobacco, acts as a potent
      addictive drug both in humans and laboratory animals, whose locomotor activity is
      also stimulated. A large body of evidence indicates that the locomotor activation
      and the reinforcing effects of nicotine may be related to its stimulatory effects
      on the mesolimbic dopaminergic function. Thus, it is now well established that
      nicotine can increase in vivo DA outflow in the nucleus accumbens and the corpus
      striatum. The stimulatory effect of nicotine on DA release most probably results
      from its ability to excite the neuronal firing rate and to increase the bursting
      activity of DA neurons in the substantia nigra pars compacta (SNc) and the
      ventral tegmental area (VTA), and from its stimulatory action on DA terminals in
      the corpus striatum and the nucleus accumbens. The neurochemical data are
      consistent with neuroanatomical findings showing the presence of nicotinic
      acetylcholine receptors (nAChRs) in the SNc, the VTA, and in projection areas of
      the central dopaminergic system such as the corpus striatum and the nucleus
      accumbens. Several lines of evidence indicate that the reinforcing properties of
      drugs of abuse, including nicotine, can be affected by a number of transmitter
      systems which may act by modulating central dopaminergic function. In this paper,
      the neurobiological mechanisms underlying nicotine addiction will be reviewed,
      and the possible strategies for new pharmacological treatments of nicotine
      dependence will be examined.

PMID- 17504236
TI  - The protease of human T-cell leukemia virus type-1 is a potential therapeutic
      target.
AB  - Human T-cell leukemia virus type-1 (HTLV-1) is associated with a number of human
      diseases. Although the mechanism by which the virus causes diseases is still not
      known, studies indicate that viral replication is critical for the development of
      HTLV-1 associated myelopathy, and initial studies suggested that blocking
      replication with reverse transcriptase inhibitors had a therapeutic effect.
      Therefore, based on the success of HIV-1 protease inhibitors, the HTLV-1 protease
      is also a potential target for chemotherapy. Furthermore, mutated residues in HIV
      1 protease that confer drug resistance are frequently seen in equivalent
      positions of other retroviral proteases, like HTLV-1 protease. Therefore,
      comparison of HTLV-1 and HIV-1 proteases is expected to aid the rational design
      of broad spectrum inhibitors effective against various retroviral proteases,
      including the mutant HIV-1 enzymes appearing in drug resistance. This review
      describes the characteristics of HTLV-1 protease, makes comparison with HIV-1
      protease, and discusses the status of inhibitor development for the HTLV-1
      protease.

PMID- 17504237
TI  - Trafficking and signalling at the synapse: where are we heading to?

PMID- 17504238
TI  - Trafficking and synaptic anchoring of ionotropic inhibitory neurotransmitter
      receptors.
AB  - Neurotransmitter receptors are subject to microtubule-based transport between
      intracellular organelles and the neuronal plasma membrane. Receptors that arrive
      at plasma membrane compartments diffuse laterally within the plane of the
      cellular surface. To achieve immobilization at their sites of action, cytoplasmic
      receptor residues bind to submembrane proteins, which are coupled to the
      underlying cytoskeleton by multiprotein scaffolds. GABA(A)Rs (gamma-aminobutyric
      type A receptors) and GlyRs (glycine receptors) are the major inhibitory
      receptors in the central nervous system. At inhibitory postsynaptic sites, all
      GlyRs and the majority of GABA(A)Rs directly or indirectly couple to gephyrin, a
      multimeric PSD (postsynaptic density) component. In addition to cluster
      formations at axo-dendritic contacts, individual GABA(A)R subtypes also anchor
      and concentrate at extrasynaptic positions, either through association with
      gephyrin or direct interaction with the ERM (ezrin/radixin/moesin) family protein
      radixin. In addition to their role in diffusion trapping of surface receptors,
      scaffold components also undergo rapid exchange to/from and between postsynaptic
      specializations, leading to a dynamic equilibrium of receptor-scaffold complexes.
      Moreover, scaffold components serve as adaptor proteins that mediate specificity
      in intracellular transport complexes. In the present review, we discuss the
      dynamic delivery, stabilization and removal of inhibitory receptors at synaptic
      sites.

PMID- 17504239
TI  - Recycling endosomes in neuronal membrane traffic.
AB  - Neurons are highly polarized cells with axonal and somatodendritic membrane
      surfaces that spatially separate signal-sending from signal-receiving membrane
      domains. As found in many other cell types, different populations of endosomes
      are involved in the sorting of synaptic and other membrane cargo in neurons. The
      exact source of the membrane for neurite extension and process remodelling during
      neuronal differentiation has remained uncertain, and we do not know exactly how
      polarized sorting of neuronal membrane proteins is achieved. In the present
      article, we will provide a brief overview of endosomes and their putative or
      proven functions in fibroblasts, epithelial cells and neurons. On the basis of
      insights from non-neuronal cell types and recent studies on the function of
      recycling endosomes during synaptic plasticity-induced membrane remodelling, we
      postulate a speculative model regarding the role of recycling endosomes in
      neuronal differentiation.

PMID- 17504240
TI  - Dial-a-mutant: web-based knockout collections for model organisms.
AB  - Although much of eukaryotic cell biology is highly conserved, the most
      biomedically relevant organisms are often the most difficult or expensive to
      study. Non-vertebrate model organisms offer a practical and accessible
      alternative. Large collections of loss-of-function mutants have now been
      generated in the nematode Caenorhabditis elegans and the angiosperm Arabidopsis
      thaliana, which can be easily accessed via the Internet. The sites reviewed in
      the present article include those of the C. elegans Knockout Consortium
      (http://celeganskoconsortium.omrf.org/) and the C. elegans National Bioresource
      Project of Japan (http://shigen.lab.nig.ac.jp/c.elegans/index.jsp), and also the
      NemaGENETAG project (http://elegans.imbb.forth.gr/nemagenetag/) for the former
      and T-DNA Express (http://signal.salk.edu/cgi-bin/tdnaexpress) for the latter.
      These sites allow one to easily identify and request C. elegans strains bearing
      mutations in approximately half of predicted genes and for essentially every
      Arabidopsis gene. These tools greatly enhance the ability of non-specialists to
      conduct studies of gene function in vivo in these model species.

PMID- 17504241
TI  - The RANTES -403G>A promoter polymorphism in Korean men: association with serum
      RANTES concentration and coronary artery disease.
AB  - In the present study we investigated the association of the RANTES (regulated
      upon activation, normal T-cell expressed and secreted) -28C>G and -403G>A
      promoter polymorphisms with the concentration of serum RANTES and CAD (coronary
      artery disease) in Korean men. We included 553 male CAD patients with (n=176) or
      without (n=377) Type 2 diabetes, aged 40-65 years with previous myocardial
      infarction ( approximately 50%) or angiographically confirmed CAD ( approximately
      50%), and 416 aged-matched healthy male controls. The main outcome measures were
      the OR (odds ratio) of CAD risk and the serum RANTES concentration evaluated by
      sandwich ELISA. Although the RANTES -28C>G genotype had no significant
      association with CAD risk, the presence of the minor allele of the RANTES -403G>A
      single nucleotide polymorphism was associated with a lower risk of CAD {OR 0.70
      [95% CI (confidence interval) 0.54-0.92], P=0.011} after adjusting for age, BMI
      (body mass index), cigarette smoking and alcohol consumption. Serum RANTES
      concentrations were significantly associated with the -403G>A genotype in
      controls (G/G: 44.7+/-3.3 ng/ml, G/A: 36.5+/-2.0 ng/ml, A/A: 28.7+/-2.5 ng/ml;
      P<0.001), non-diabetic CAD patients (G/G: 50.9+/-3.0 ng/ml, G/A: 42.2+/-2.6
      ng/ml, A/A: 41.3+/-4.4 ng/ml; P<0.05) and diabetic CAD patients (G/G: 58.5+/-3.5
      ng/ml, G/A: 49.6+/-4.1 ng/ml, A/A: 42.2+/-4.3 ng/ml; P<0.05); however, such
      associations were not observed in the subgroup of CAD patients taking lipid
      lowering medication. Moreover, serum RANTES was positively correlated with C
      reactive protein (r=0.289, P<0.001) and platelet counts (r=0.253, P<0.001). The
      results of the present study demonstrate that the RANTES -403A allele is
      associated with lower serum RANTES concentrations and consequently with reduced
      CAD risk.

PMID- 17504242
TI  - Impact of age on the vasovagal response provoked by sublingual nitroglycerine in
      routine tilt testing.
AB  - NTG (nitroglycerine) is used in routine tilt testing to elicit a vasovagal
      response. In the present study we hypothesized that with increasing age NTG
      triggers a more gradual BP (blood pressure) decline due to a diminished
      baroreflex-buffering capacity. The purpose of the present study was to examine
      the effect of NTG on baroreflex control of BP in patients with distinct age
      related vasovagal collapse patterns. The study groups consisted of 29 patients
      (16-71 years old, 17 females) with clinically suspected VVS (vasovagal syncope)
      and a positive tilt test. Mean FAP (finger arterial pressure) was monitored
      continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output)
      and SVR (systemic vascular resistance) were computed from the pressure pulsations
      (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In
      the first 3 min after NTG administration, BP was well-maintained in all patients.
      This implied an adequate arterial resistance response to compensate for steeper
      reductions in SV and CO with increasing age. HR (heart rate) increased and the
      BRS decreased after NTG administration. The rate of mean FAP fall leading to
      presyncope was inversely related to age (r=0.51, P=0.005). Accordingly, patients
      with a mean FAP fall >1.44 mmHg/s (median) were generally younger compared with
      patients with a slower mean FAP-fall (30+/-10 years compared with 51+/-17 years;
      P=0.001). The main determinant of the rate of BP fall on approach of presyncope
      was the rate of fall in HR (r=0.75, P<0.001). It was concluded that, in older
      patients, sublingual NTG provokes a more gradual BP decline compared with younger
      patients. This gradual decline cannot be ascribed to failure of the baroreflex
      buffering capacity with increasing age. Age-related differences in the laboratory
      presentation of a vasovagal episode depend on the magnitude of the underlying
      bradycardic response.

PMID- 17504243
TI  - The orf4 gene of the enterobacterial ICE, R391, encodes a novel UV-inducible
      recombination directionality factor, Jef, involved in excision and transfer of
      the ICE.
AB  - The enterobacterial mobile genetic element R391, the prototype ICE (integrating
      conjugative element) of the SXT/R391 family, shows increased conjugative transfer
      following UV irradiation. This is dependent on a functioning R391 orf4 gene,
      which is adjacent to the element encoded integrase gene, int. orf4 mutants fail
      to form a detectable circular transfer intermediate, do not show UV induced
      transfer and show a much reduced general transfer ability. The orf4 gene product,
      termed Jef (IncJ excision factor), shows little homology to anything currently in
      the nucleotide or protein databases. It is predicted to encode a 66 amino acid,
      8.03 kDa, basic, DNA-binding protein with an iso-electric point of pH 8.1: these
      characteristics being similar to those of recombinational directionality factors
      involved in excision. Jef expression is up-regulated upon UV irradiation as
      demonstrated by real-time reverse transcriptase PCR and is controlled by two
      element encoded genes orf90 and orf91, which show similarity to the
      transcriptional activator complex FlhC and FlhD. orf4, orf90 and orf91 are
      conserved in all the SXT/R391-like elements sequenced to date including SXT,
      ICESpuPO1 and ICEVchMex1. orf4 is also conserved in other SXT/R391 family members
      such as R997, R392, R705 and pMERPH as shown by sequencing amplicons from these
      ICEs generated using orf4 specific primers.

PMID- 17504244
TI  - Strain- and region-specific gene expression profiles in mouse brain in response
      to chronic nicotine treatment.
AB  - A pathway-focused complementary DNA microarray and gene ontology analysis were
      used to investigate gene expression profiles in the amygdala, hippocampus,
      nucleus accumbens, prefrontal cortex (PFC) and ventral tegmental area of C3H/HeJ
      and C57BL/6J mice receiving nicotine in drinking water (100 mug/ml in 2%
      saccharin for 2 weeks). A balanced experimental design and rigorous statistical
      analysis have led to the identification of 3.5-22.1% and 4.1-14.3% of the 638
      sequence-verified genes as significantly modulated in the aforementioned brain
      regions of the C3H/HeJ and C57BL/6J strains, respectively. Comparisons of
      differential expression among brain tissues showed that only a small number of
      genes were altered in multiple brain regions, suggesting presence of a brain
      region-specific transcriptional response to nicotine. Subsequent principal
      component analysis and Expression Analysis Systematic Explorer analysis showed
      significant enrichment of biological processes both in C3H/HeJ and C57BL/6J mice,
      i.e. cell cycle/proliferation, organogenesis and transmission of nerve impulse.
      Finally, we verified the observed changes in expression using real-time reverse
      transcriptase polymerase chain reaction for six representative genes in the PFC
      region, providing an independent replication of our microarray results. Together,
      this report represents the first comprehensive gene expression profiling
      investigation of the changes caused by nicotine in brain tissues of the two mouse
      strains known to exhibit differential behavioral and physiological responses to
      nicotine.

PMID- 17504245
TI  - Social and sexual incentive properties of estrogen receptor alpha, estrogen
      receptor beta, or oxytocin knockout mice.
AB  - Social and sexual incentive motivation, defined as the intensity of approach to a
      social and a sexual incentive, respectively, were studied in female Swiss Webster
      mice. In the first experiment, the social incentive was a castrated mouse of the
      same strain as the females, whereas the sexual incentive was an intact male mouse
      of the same strain. Ovariectomized females were first tested after oil treatment
      and then after administration of estradiol benzoate + progesterone in doses
      sufficient to induce full receptivity. The hormones increased sexual incentive
      motivation while leaving social incentive motivation unaffected. This suggests
      that sexual incentive motivation in the female mouse is dependent on ovarian
      hormones. In the next experiment, ovariectomized females were tested with an
      intact, male estrogen receptor alpha knockout and its wild type as incentives,
      first without hormones and then when fully receptive. There were no differences
      in incentive properties between the wild type and the knockout. In a similar
      experiment, we used an intact male estrogen receptor beta knockout and its
      corresponding wild type as incentives. The wild type turned out to be a more
      attractive social incentive than the knockout, while they were equivalent as
      sexual incentives. Finally, an intact male oxytocin knockout and its wild type
      were used as incentives. The knockout turned out to be a superior incentive,
      particularly a superior sexual incentive. The fact that the estrogen receptor
      beta and oxytocin knockouts have incentive properties different from their wild
      types may be important to consider in studies of these knockouts' sociosexual
      behaviors.

PMID- 17504246
TI  - Genetic variation in COMT and PRODH is associated with brain anatomy in patients
      with schizophrenia.
AB  - Haploinsufficiency of 22q11 genes including catechol-O-methyltransferase (COMT)
      and proline dehydrogenase (PRODH) may result in structural and functional brain
      abnormalities and increased vulnerability to schizophrenia as observed in
      patients with microdeletions of 22q11. Thus, COMT and PRODH could be modifier
      genes for schizophrenia. We examined association of polymorphisms in COMT and
      PRODH with brain anatomy in young patients with schizophrenia and schizoaffective
      disorder. We acquired structural magnetic resonance imaging data from 51 male
      patients and genotyped two single nucleotide polymorphisms (SNPs) in the COMT
      gene and three in the PRODH gene. Statistical Parametric Mapping software and
      optimized voxel-based morphometry were used to determine regional gray matter
      (GM) and white matter (WM) density differences, and total GM and WM volume
      differences between genotype groups. Two nonsynonymous SNPs in the PRODH gene
      were associated with bilateral frontal WM density reductions and an SNP in the P2
      promoter region of COMT (rs2097603) was associated with GM increase in the right
      superior temporal gyrus. Furthermore, we found evidence for COMT and PRODH
      epistasis: in patients with a COMT Val allele (rs4680) and with one or two
      mutated PRODH alleles, we observed increased WM density in the left inferior
      frontal lobe. Our results suggest that genetic variation in COMT and PRODH has
      significant effects on brain regions known to be affected in schizophrenia.
      Further research is needed to investigate the role of 22q11 genes on brain
      structure and function and their role in vulnerability for schizophrenia.

PMID- 17504247
TI  - Association study of the nicotinic acetylcholine receptor alpha4 subunit gene,
      CHRNA4, in attention-deficit hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common childhood-onset
      psychiatric condition with a strong genetic component. Evidence from
      pharmacological, clinical and animal studies has suggested that the nicotinic
      system could be involved in the disorder. Previous studies have implicated the
      nicotinic acetylcholine receptor alpha4 subunit gene, CHRNA4, in ADHD.
      Particularly, a polymorphism in the exon 2-intron 2 junction of CHRNA4 has been
      associated with severe inattention defined by latent class analysis. In the
      current study, we used the transmission disequilibrium test (TDT) to investigate
      four polymorphisms encompassing this region of CHRNA4 for association with ADHD
      in a sample of 264 nuclear families from Toronto. No significant evidence of
      biased transmission was observed for any of the marker alleles for ADHD defined
      as a categorical trait (all subtypes included), although one haplotype showed
      marginal evidence of under-transmission. No association was found with the ADHD
      predominantly inattentive subtype or with symptom dimension scores of
      inattention. On the contrary, nominally significant evidence of association of
      individual markers was obtained for the ADHD combined subtype and with teacher
      rated hyperactivity-impulsivity scores, with the same haplotype being under
      transmitted. Based on our results and others, CHRNA4 may be involved in ADHD;
      however, its role in ADHD symptomatology remains to be clarified.

PMID- 17504248
TI  - Serotonin receptor genes 5HT1A and 5HT2A modify the relation between childhood
      temperament and adulthood hostility.
AB  - We examined a modifying role of 5HT1A and 5HT2A receptors in the relation between
      childhood difficult temperament and adulthood hostility in 729 subjects derived
      from a population-based sample. Subjects were 3-12 years when their childhood
      temperaments consisting of hyperactivity, low sociability and negative
      emotionality (i.e. the difficult temperament), were assessed by their mothers.
      Their adulthood hostility comprising anger, cynicism and paranoia, was measured
      twice, 17 and 21 years later. It was found that the 5HT1A and 5HT2A receptors
      were not related to childhood temperament or to adult hostility, but they
      modified the association between childhood hyperactivity and adult hostility in
      men. Male carriers of T/T genotype of 5HTR2A who were rated hyperactive by their
      mothers expressed a high level of hostility, especially that of cynicism, in
      adulthood. For men with other genetic variants, such an association was not seen.
      This finding was consistent across the two follow-ups 4 years apart. Further
      research is needed to clarify whether mother-related hyperactivity adequately
      describes the temperament of the child or is a reflection of mother's hostile
      child-rearing attitudes.

PMID- 17504249
TI  - Novel alpha7 nicotinic receptor isoforms and deficient cholinergic transcription
      in schizophrenia.
AB  - Abnormal alpha7 nicotinic acetylcholine receptor activity contributes to sensory
      gating and cognitive deficits in schizophrenic individuals. Negligible
      differences in alpha7 mRNA levels between disease and control states have led to
      conclusions that cholinergic dysfunction in schizophrenia (SZ) must occur post
      transcriptionally. Alternatively, we propose that the dysregulation of splice
      variants of the alpha7 receptor could account for cholinergic deficiencies
      observed in this disease. Here, we isolated multiple alpha7 splice variants
      including exon deletions and those associated with a novel 124-127 base insertion
      following exon 4. Transcripts containing this new exon originated from sense
      strand-oriented RNA (vs. antisense), and in silico translations produced putative
      subunits with unique amino termini. Quantitative real-time polymerase chain
      reaction analyses indicated that one novel isoform was significantly
      downregulated (P < or = 0.03) in post-mortem prefrontal cortex of individuals
      with SZ (n = 35) compared with controls (n = 34). Ten brain regions (cerebellum,
      thalamus, corpus callosum, caudate, putamen and five areas of the cortex) were
      further screened for alpha7 isoforms in three individuals of each group.
      Semiquantitative analyses showed that each alpha7 mRNA subtype was present in
      each brain region, but all were particularly deficient in the corpus callosum in
      schizophrenics vs. controls (P < or = 0.0002 to 0.05 for different isoforms). Our
      data demonstrate that alpha7 transcription is altered in several ways in SZ,
      suggesting that transcription-level mechanisms could account in part for the
      impaired cholinergic neurotransmission observed in this disease.

PMID- 17504250
TI  - COMT Val(158)Met and 5HTTLPR functional loci interact to predict persistence of
      anxiety across adolescence: results from the Victorian Adolescent Health Cohort
      Study.
AB  - We investigated whether a composite genetic factor, based on the combined actions
      of catechol-O-methyltransferase (COMT) (Val(158)Met) and serotonin transporter
      (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict
      persistence of anxiety across adolescence than either locus in isolation.
      Analyses were performed on DNA collected from 962 young Australians participating
      in an eight-wave longitudinal study of mental health and well-being (Victorian
      Adolescent Health Cohort Study). When the effects of each locus were examined
      separately, small dose-response reductions in the odds of reporting persisting
      generalized (free-floating) anxiety across adolescence were observed for the COMT
      Met(158) [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76-0.95, P =
      0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79-0.99, P = 0.033). There
      was no evidence for a dose-response interaction effect between loci. However,
      there was a double-recessive interaction effect in which the odds of reporting
      persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI =
      0.29-0.70, P < 0.001) among carriers homozygous for both the COMT Met(158) and
      the 5HTTLPR Short alleles (Met(158)Met + Short-Short) compared with the remaining
      cohort. The double-recessive effect remained after multivariate adjustment for a
      range of psychosocial predictors of anxiety. Exploratory stratified analyses
      suggested that genetic protection may be more pronounced under conditions of high
      stress (insecure attachments and sexual abuse), although strata differences did
      not reach statistical significance. By describing the interaction between genetic
      loci, it may be possible to describe composite genetic factors that have a more
      substantial impact on psychosocial development than individual loci alone, and in
      doing so, enhance understanding of the contribution of constitutional processes
      in mental health outcomes.

PMID- 17504252
TI  - Radiofrequency lesions made in canine and swine atria at the proximal coronary
      sinus prevent rapid pacing-induced atrial fibrillation.

PMID- 17504253
TI  - Left atrial appendage activity mimicking an epsilon wave on the surface
      electrocardiogram.

PMID- 17504254
TI  - Mechanisms of recurrent atrial fibrillation: comparisons between segmental ostial
      versus circumferential pulmonary vein isolation.
AB  - BACKGROUND: Electrical isolation of pulmonary veins (PVs) is an effective therapy
      for atrial fibrillation (AF). Both segmental ostial PV ablation and
      circumferential ablation with PV-left atrial (LA) block have been implicated to
      eliminate AF. However, the mechanism of the recurrent AF after undergoing either
      strategy remains unclear. METHODS AND RESULTS: Of the 73 consecutive patients
      with symptomatic AF that underwent PV isolation and had recurrences of AF, Group
      1 consisted of 46 patients (age 56 +/- 13 years old, 35 males) who underwent PV
      isolation by segmental ostial PV ablation and Group 2 consisted of 27 patients
      (age 51 +/- 11 years old, 24 males) who underwent circumferential ablation with
      PV-LA block. In Group 1, the earliest ectopic beat or ostial PV potentials were
      targeted. In Group 2, circumferential ablation with PV-LA block was performed by
      encircling the extraostial regions around the left and right PVs. During the
      first procedure, all patients had PV-AF. There was no difference in the non-PV
      ectopy between Group 1 and Group 2. During the second procedure, the incidence of
      an LA posterior wall ectopy initiating AF was significantly lower (20% vs. 0%, P
      = 0.01) in Group 2. There was no difference in the PV ectopy initiating AF during
      the second procedure. CONCLUSION: Circumferential ablation of AF with PV-LA block
      may eliminate the LA posterior wall ectopy and decrease the incidence of LA
      posterior wall ectopy initiating AF during the second procedure.

PMID- 17504255
TI  - Amiodarone therapy for atrial rhythm control: insights gained from a single
      center experience.
AB  - INTRODUCTION: Amiodarone has been advocated as an effective "long-term" therapy
      for atrial rhythm control in patients with atrial fibrillation (AF). We sought to
      assess the sustainability of this therapeutic strategy. METHODS AND RESULTS:
      Retrospective analysis of a consecutive, single-center cohort (n = 168) with
      symptomatic AF who were treated with amiodarone and followed for 3 years. The
      incidence of amiodarone cessation was evaluated at 1, 2, and 3 years and
      attributed principally to drug inefficacy, intolerance, or toxicity. A gradual
      diminution in the number of patients on therapy was observed, such that by 3
      years, only 45% remained. This was attributable to inefficacy (25%), intolerance
      (12%), or toxicity (18%). Pulmonary toxicity was surprisingly common, occurring
      in at least 7% of patients. CONCLUSIONS: These data challenge the notion of
      amiodarone as a reasonable "destination" therapy for AF.

PMID- 17504256
TI  - Plateau waveform shape allows a much higher patient shock energy tolerance in AF
      patients.
AB  - OBJECTIVES: To evaluate the possible pain reduction of the plateau waveform in
      atrial fibrillation (AF) patients. BACKGROUND: Previous studies have indicated
      that reduced amplitude waveforms would be less painful than a conventional
      (65/65% tilt) biphasic waveform. Computer modeling suggested that a moderately
      long (10-12 msec) plateau (flat topped) shock waveform would deliver equivalent
      effectiveness with the lowest possible peak amplitude. METHODS: We enrolled 27
      patients at two sites with persistent AF with a total of 220 shocks delivered
      during internal atrial cardioversion using an interleaved crossover design.
      Patient response was scored in three ways: (1) a verbally reported discomfort
      score, (2) visual analog scale (VAS), and (3) a blinded observer reporting a
      contraction score. RESULTS: All scores were significantly reduced (P < 0.0001) by
      the plateau waveform with impressive statistics: Verbal discomfort (3.51 +/- 0.13
      to 2.89 +/- 0.12), VAS (7.00 +/- 0.56 to 5.91 +/- 0.36), and contraction scores
      (1.94 +/- 0.12 to 1.62 +/- 0.12). The average pain threshold shift (TS) for the
      Verbal score was 2.34, while that for the VAS score was 2.30. (This means that
      the patient typically could tolerate 2.34 times as much energy with the plateau
      waveform for the same level of verbally reported discomfort.) The contraction TS
      was less at 1.57. Response scores were also corrected for the shock sequence
      number to control for the sensitization effect from multiple shocks. This
      increased the TS for the Verbal score to 3.58, but the shock number was not
      significant for the VAS. A pulmonary artery electrode return was associated with
      lower pain compared with a coronary sinus position. CONCLUSION: A plateau shaped
      biphasic waveform resulted in significantly increased shock energy pain
      tolerances. Controlling for session sensitization, patients tolerated over three
      times as much energy for the same verbally reported discomfort score.

PMID- 17504257
TI  - A case of preexcitation?

PMID- 17504258
TI  - Bi-focal atrial tachycardia mimicking atrial fibrillation: fusion and
      interference between two distinct tachycardias.
AB  - Irregular tachycardias mimicking atrial fibrillation (AF) have previously been
      described. We report a case of a 60-year-old man with an antiarrhythmic drug
      resistant atrial tachycardia (AT) mimicking AF. The tachycardia consisted of two
      distinct ATs with interference of one repetitive AT with another sustained AT.
      Radiofrequency (RF) ablation of two distinct right atrial foci eliminated the
      irregular tachycardia. Although catheter-based pulmonary vein isolation has
      become a popular therapeutic approach for patients with symptomatic AF, careful
      evaluation of the intracardiac recordings in the patients undergoing RF ablation
      for AF is important.

PMID- 17504259
TI  - Role of sodium channels in propagation in heart muscle: how subtle genetic
      alterations result in major arrhythmic disorders.
AB  - Sodium channels play a crucial role in initiation, propagation, and maintenance
      of cardiac excitation throughout the heart. Indeed, dysfunctional sodium channels
      have been shown to be responsible for several inherited cardiac electrical
      disorders, such as Long QT and Brugada syndromes (BrS), potentially leading to
      fatal arrhythmic events. Genetic approaches and functional experiments using
      heterologous systems have enabled the characterization of the molecular
      determinants involved in these disorders and their consequences on ion channel
      function. The improved understanding of the mechanisms leading to these cardiac
      arrhythmic events represents a first step in the development of therapeutic
      treatments.

PMID- 17504260
TI  - Expression of Toll-like receptor 4 in rat liver during the course of carbon
      tetrachloride-induced liver injury.
AB  - BACKGROUND AND AIM: It has recently been reported that Toll-like receptor 4
      (TLR4) is involved in cellular responses to lipopolysaccharides (LPS) and early
      liver injury induced by LPS. The aim of the present study was to investigate the
      alterations of TLR4 gene expression in liver tissues and Kupffer cells during the
      course of carbon tetrachloride (CCl(4))-induced chronic liver injury and fibrosis
      and its role in liver injury. METHODS: Rats were induced with liver injury and
      fibrosis by CCl(4) administered subcutaneously twice weekly for up to 8 weeks.
      The Kupffer cells were isolated by the combined collagenase-pronase perfusion
      method and incubated with varying doses of LPS. The mRNA expression of TLR4 in
      liver tissues and Kupffer cells was measured by reverse transcriptase polymerase
      chain reaction. The levels of tumor necrosis factor (TNF)-alpha in Kupffer cell
      culture supernatants were determined by enzyme-linked immunosorbent assay. The
      plasma levels of the endotoxin were determined by chromogenic substrate limulus
      amebocyte lysate assay. The association of the endotoxin receptor expression with
      plasma endotoxin levels was assessed. RESULTS: CCl(4) administration elicited
      extensive changes in liver morphology, including steatosis, inflammation,
      necrosis, and fibrosis. Low levels of TLR4 mRNA were detected in normal rat liver
      tissues, but no expression was detected in the Kupffer cells. The expression of
      TLR4 mRNA in liver tissues and Kupffer cells was increased 2 weeks after CCl(4)
      administration, peaked at 4 and 6 weeks, and declined at 8 weeks. Basic TNF-alpha
      production of Kupffer cells isolated from CCl(4)-treated rats at 4 and 6 weeks
      was significantly higher than that of normal rats (P < 0.05). Upon LPS
      stimulation, production of TNF-alpha was markedly increased in Kupffer cells
      isolated from normal and 2-,4-, and 6-week CCl(4)-treated rats. Moreover, LPS
      induced TNF-alpha production was dose-dependent. The plasma levels of the
      endotoxin were increased during the time of liver injury. There was a correlation
      between plasma endotoxin levels and TLR4 gene expression in the early and middle
      stage of liver injury. CONCLUSION: The gene expression of TLR4 was upregulated
      during the course of CCl(4)-induced liver injury, which is associated with the
      degree of liver injury and Kupffer cell activation. The gut-derived endotoxin may
      be involved in the upregulation of TLR4 expression.

PMID- 17504261
TI  - Protective effect of glucosamine against ibuprofen-induced peptic ulcer in rats.
AB  - BACKGROUND: Helicobacter pylori is the major causative factor of ulcer but the
      use of ibuprofen and other non-steroidal anti-inflammatory drugs have also been
      implicated in development of ulcer. The purpose of the present study was to
      determine the anti-ulcer effect of glucosamine. METHODS: The protective effect of
      glucosamine on ibuprofen-induced peptic ulcer in male albino rats was studied
      with respect to changes in the volume of gastric juice, acid output, pepsin
      activity, activities of membrane bound ATPases, protein content, glycoprotein
      components and histopathology. RESULTS: Oral administration of ibuprofen caused
      significant increase in the number of lesions in the gastric mucosa, increases in
      the volume of gastric juice and acidity, and decreased activity of pepsin. The
      levels of protein content and glycoprotein components (hexose, hexosamine and
      sialic acid) and ATPase activities were also observed. Oral pretreatment with
      glucosamine resulted in significant reduction in the number of lesions in the
      gastric mucosa and decreases in the volume of gastric juice and acidity. The
      pepsin activity was also maintained at near normalcy. Prior oral administration
      of glucosamine significantly prevented the ibuprofen-induced depletion of protein
      and glycoprotein components and maintained the activities of membrane bound
      ATPases as compared to untreated ulcer induced group of rats. CONCLUSION: The
      anti-ulcerogenic activity of glucosamine might be ascribable to its ability to
      neutralize the hydrochloric acid secreted into the stomach and to its capability
      to strengthen the mucosal barrier by increasing mucosal glycoprotein synthesis
      and to its free radical scavenging property. Histopathological investigations of
      the mucosal tissue also support the anti-ulcerogenic effect of glucosamine.

PMID- 17504262
TI  - Sub-cellular localization of insulin-regulated membrane aminopeptidase, IRAP to
      vesicles in neurons.
AB  - Angiotensin IV and LVV-hemorphin 7 promote robust enhancing effects on learning
      and memory. These peptides are also competitive inhibitors of the insulin
      regulated membrane aminopeptidase, suggesting that the biological actions of
      these peptides may result from inhibition of IRAP activity. However, the normal
      function of IRAP in the brain is yet to be determined. The present study
      investigated the sub-cellular distribution of IRAP in four neuronal cell lines
      and in the mouse brain. Using sub-cellular fractionation, IRAP was found to be
      enriched in low density microsomes, while lower levels of IRAP were also present
      in high density microsomes, plasma membrane and mitochondrial fractions. Dual
      label immunohistochemistry confirmed the presence of IRAP in vesicles co
      localized with the vesicular maker VAMP2, in the trans Golgi network co-localized
      with TGN 38 and in endosomes co-localized with EEA1. Finally using electron
      microscopy, IRAP specific immunoreactivity was predominantly associated with
      large 100-200 nm vesicles in hippocampal neurons. The location, appearance and
      size of these vesicles are consistent with neurosecretory vesicles. IRAP
      precipitate was also detected in intracellular structures including the rough
      endoplasmic reticulum, Golgi stack and mitochondrial membranes. The sub-cellular
      localization of IRAP in neurons demonstrated in the present study bears striking
      parallels with distribution of IRAP in insulin responsive cells, where the enzyme
      plays a role in insulin-regulated glucose uptake. Therefore, we propose that the
      function of IRAP in neurons may be similar to that in insulin responsive cells.

PMID- 17504263
TI  - Alanine metabolism, transport, and cycling in the brain.
AB  - Brain glutamate/glutamine cycling is incomplete without return of ammonia to
      glial cells. Previous studies suggest that alanine is an important carrier for
      ammonia transfer. In this study, we investigated alanine transport and metabolism
      in Guinea pig brain cortical tissue slices and prisms, in primary cultures of
      neurons and astrocytes, and in synaptosomes. Alanine uptake into astrocytes was
      largely mediated by system L isoform LAT2, whereas alanine uptake into neurons
      was mediated by Na(+)-dependent transporters with properties similar to system
      B(0) isoform B(0)AT2. To investigate the role of alanine transport in metabolism,
      its uptake was inhibited in cortical tissue slices under depolarizing conditions
      using the system L transport inhibitors 2-aminobicyclo[2.2.1]heptane-2-carboxylic
      acid and cycloleucine (1-aminocyclopentanecarboxylic acid; cLeu). The results
      indicated that alanine cycling occurs subsequent to glutamate/glutamine cycling
      and that a significant proportion of cycling occurs via amino acid transport
      system L. Our results show that system L isoform LAT2 is critical for alanine
      uptake into astrocytes. However, alanine does not provide any significant carbon
      for energy or neurotransmitter metabolism under the conditions studied.

PMID- 17504264
TI  - Ikaros is expressed in developing striatal neurons and involved in
      enkephalinergic differentiation.
AB  - The Ikaros (Ik) gene encodes alternatively spliced zinc-finger proteins
      originally identified in developing hematopoietic organs and acts as master
      regulator of lymphoid development. During our search for transcription factors
      that control the developmental expression of the enkephalin (ENK) gene we found
      that Ik-1 and Ik-2 isoforms are specifically expressed in the embryonic striatum
      and bind the Ik-like cis-regulatory DNA element present on the ENK gene. Ik
      proteins are expressed by both proliferating (BrdU+/nestin+) and by post-mitotic
      differentiating (MAP2+) cells in the developing striatum between embryonic day 12
      and post-natal day 2 and mRNAs encoding for the Ik and ENK genes are co-expressed
      by a subset of differentiating striatal neurons. Blocking the DNA binding of Ik
      proteins in differentiating embryonic striatal neuronal cultures resulted in
      decreased ENK expression and mutant animals lacking the DNA-binding domain of Ik
      had a deficit in the number of ENK but not in dynorphin or substance P mRNA+
      cells. Animals lacking the protein interaction domain of Ik showed no deficit.
      These results demonstrate that Ik-1 and Ik-2 proteins through their DNA binding
      act as positive regulators of ENK gene expression in the developing striatum and
      participate in regulating enkephalinergic differentiation.

PMID- 17504266
TI  - Folate deprivation increases presenilin expression, gamma-secretase activity, and
      Abeta levels in murine brain: potentiation by ApoE deficiency and alleviation by
      dietary S-adenosyl methionine.
AB  - Folate deficiency has been associated with age-related neurodegeneration. One
      direct consequence of folate deficiency is a decline in the major methyl donor, S
      adenosyl methionine (SAM). We demonstrate herein that dietary deficiency in
      folate and vitamin E, coupled pro-oxidant stress induced by dietary iron,
      increased presenilin-1 expression, gamma-secretase activity, and Abeta levels in
      normal adult mice. These increases were potentiated by apolipoprotein E
      deficiency as shown by treatment of transgenic mice homozygously lacking murine
      apolipoprotein E. Dietary supplementation with SAM in the absence of folate
      attenuated or alleviated these deleterious consequences. These findings link
      nutritional and genetic risk factors for age-related neurodegeneration and
      underscore that dietary supplementation with SAM may be useful to augment
      therapeutic approaches.

PMID- 17504265
TI  - Glutamine uptake by System A transporters maintains neurotransmitter GABA
      synthesis and inhibitory synaptic transmission.
AB  - GABA synthesis is necessary to maintain synaptic vesicle filling, and key
      proteins in its biosynthetic pathways may play a role in regulating inhibitory
      synaptic stability and strength. GABAergic neurons require a source of precursor
      glutamate, possibly from glutamine, although it is controversial whether
      glutamine contributes to the synaptic pool of GABA. Here we report that
      inhibition of System A glutamine transporters with alpha-(methyl-amino)
      isobutyric acid rapidly reduced the amplitude of inhibitory post-synaptic
      currents and miniature inhibitory post-synaptic currents (mIPSCs) recorded in rat
      hippocampal area cornu ammonis 1 (CA1) pyramidal neurons, indicating that
      synaptic vesicle content of GABA was reduced. After inhibiting astrocytic
      glutamine synthesis by either blocking glutamate transporters or the glutamine
      synthetic enzyme, the effect of alpha-(methyl-amino) isobutyric acid on mIPSC
      amplitudes was abolished. Exogenous glutamine did not affect mIPSC amplitudes,
      suggesting that the neuronal transporters are normally saturated. Our findings
      demonstrate that a constitutive supply of glutamine is provided by astrocytes to
      inhibitory neurons to maintain vesicle filling. Therefore, glutamine
      transporters, like those for glutamate, are potential regulators of inhibitory
      synaptic strength. However, in contrast to glutamate, extracellular glutamine
      levels are normally high. Therefore, we propose a supportive role for glutamine,
      even under resting conditions, to maintain GABA vesicle filling.

PMID- 17504267
TI  - A comparative study of proteasomal inhibition and apoptosis induced in N27
      mesencephalic cells by dopamine and MG132.
AB  - Dopamine (DA) and its metabolites have been implicated in the pathogenesis of
      Parkinson's disease. DA can produce reactive-oxygen species and DA-derived
      quinones such as aminochrome can induce proteasomal inhibition. We therefore
      examined the ability of DA and MG132 to induce apoptosis and proteasomal
      inhibition in N27 rat dopaminergic cells. DA (0-500 micromol/L, 0-24 h) and MG132
      (0-5 micromol/L, 0-24 h) treated N27 cells resulted in time- and concentration
      dependent apoptosis. To better define DA and MG132-induced apoptosis, the
      activation of initiator caspases 2 and caspase 9 and the executioner caspase 3
      was investigated. Activation of caspase 2, caspase 9, and caspase 3 occurred
      early and prior to cell death. In addition, N-acetylcysteine (NAC) blocked DA but
      not MG132-induced apoptosis and mitochondrial membrane potential loss. NAC can
      react with both reactive-oxygen and quinoid metabolites and its inhibitory
      activity suggests a role for reactive species in DA-induced apoptosis.
      Proteasomal inhibition was detected after DA treatment in N27 cells which
      occurred prior to cell death and was abrogated by NAC. Our results implicate DA
      derived reactive species in proteasomal inhibition and caspase-dependent
      apoptosis in N27 cells. The ability of endogenous DA-derived metabolites to
      induce proteasomal inhibition and apoptosis may contribute to the selective loss
      of dopaminergic neurons in Parkinson's disease.

PMID- 17504271
TI  - A model for clubfoot based on micro-CT data.
AB  - The pathological anatomy of idiopathic clubfoot has been investigated for more
      than 180 years using anatomy, computed tomography (CT), histology and microscopy.
      Seven idiopathic clubfeet and two normal feet of aborted fetuses were dissected
      in the present study, with special emphasis on the shape of the cartilage and
      bones. A three-dimensional (3D) micro-CT system, which generates a series of X
      ray attenuation measurements, was used to produce computed reconstructed 3D data
      sets of each of the separated bones. Based on the micro-CT data scans a high
      definition 3D colour printing system was used to make a four times enlarged
      clubfoot model, precisely presenting all the bony malformations. This model
      reflects the complexity of the anatomy of this disease and is designed to be used
      in the workshops of orthopaedic surgeons and physiotherapists, for training in
      new surgical and manipulation techniques.

PMID- 17504270
TI  - Excitotoxic damage to white matter.
AB  - Glutamate kills neurons by excitotoxicity, which is caused by sustained
      activation of glutamate receptors. In recent years, it has been shown that
      glutamate can also be toxic to white matter oligodendrocytes and to myelin by
      this mechanism. In particular, glutamate receptor-mediated injury to these cells
      can be triggered by activation of alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid, kainate and N-methyl-D-aspartate glutamate receptor types. Thus,
      these receptor classes, and the intermediaries of the signal cascades they
      activate, are potential targets for drug development to treat white matter damage
      in acute and chronic diseases. In addition, alterations of glutamate homeostasis
      in white matter can determine glutamate injury to oligodendrocytes and myelin.
      Astrocytes are responsible for most glutamate uptake in synaptic and non-synaptic
      areas and consequently are the major regulators of glutamate homeostasis.
      Activated microglia in turn may secrete cytokines and generate radical oxygen
      species, which impair glutamate uptake and reduce the expression of glutamate
      transporters. Finally, oligodendrocytes also contribute to glutamate homeostasis.
      This review aims at summarizing the current knowledge about the mechanisms
      leading to oligodendrocyte cell death and demyelination as a consequence of
      alterations in glutamate signalling, and their clinical relevance to disease. In
      addition, we show evidence that oligodendrocytes can also be killed by ATP acting
      at P2X receptors. A thorough understanding of how oligodendrocytes and myelin are
      damaged by excitotoxicity will generate knowledge that can lead to improved
      therapeutic strategies to protect white matter.

PMID- 17504269
TI  - Glutamate-mediated neuronal-glial transmission.
AB  - The brain is the most complex organ of the human body. It is composed of several
      highly specialized and heterogeneous populations of cells, represented by
      neurones (e.g. motoneurons, projection neurons or interneurons), and glia
      represented by astrocytes, oligodendrocytes and microglia. In recent years there
      have been numerous studies demonstrating close bidirectional communication of
      neurons and glia at structural and functional levels. In particular, the
      excitatory transmitter glutamate has been shown to evoke a variety of responses
      in astrocytes and oligodendrocytes in the healthy as well as the diseased brain.
      Here we overview the multitude of glutamate sensing molecules expressed in glia
      and describe some general experiments which have been performed to identify the
      glutamate-responsive molecules, i.e. the ionotropic and metabotropic glutamate
      receptors as well as the glutamate transporters. We also discuss a transgenic
      mouse model that permits detailed and specific investigations of the role of
      glial glutamate receptors.

PMID- 17504272
TI  - Differential signal transduction via TrmB, a sugar sensing transcriptional
      repressor of Pyrococcus furiosus.
AB  - TrmB is a transcriptional repressor of the hyperthermophilic archaeon Pyrococcus
      furiosus serving at least two operons. TrmB represses genes encoding an ABC
      transporter for trehalose and maltose (the TM system) with trehalose and maltose
      as inducers. TrmB also represses genes encoding another ABC transporter for
      maltodextrins (the MD system) with maltotriose and sucrose as inducers. Here we
      report that glucose which was also bound by TrmB acted as a corepressor (causing
      stronger repression) for both the TM and the MD system. Binding of glucose by
      TrmB was increased in the presence of TM promoter DNA. Maltose which acted as
      inducer for the TM system acted as a corepressor for the MD system intensifying
      repression. We propose that the differential conformational changes of TrmB in
      response to binding the different sugars governs the ability of TrmB to interact
      with the promoter region and represents a simple mechanism for selecting the
      usage of one carbon source over the other, reminiscent of catabolite repression
      in bacteria.

PMID- 17504274
TI  - Combating the obesity epidemic: cultural problems demand cultural solutions.

PMID- 17504273
TI  - Cardiolipin promotes polar localization of osmosensory transporter ProP in
      Escherichia coli.
AB  - The osmolality required to activate osmosensory transporter ProP and the
      proportion of cardiolipin (CL) among the phospholipids of Escherichia coli rise
      with growth medium osmolality. Most CL synthesis has been attributed to the cls
      gene product. Transcription of cls increased with osmolality. The proportion of
      CL was low and osmolality-independent in cls(-) bacteria. It increased more
      dramatically on the transition to stationary phase in cls(-) than cls(+)
      bacteria. Thus, Cls is responsible for osmoregulated CL synthesis and other
      enzymes may contribute to CL accumulation during stationary phase. The proportion
      of phosphatidylglycerol (PG) was elevated and it increased with medium osmolality
      in cls(-) bacteria. A cls defect impaired growth of E. coli on solid and in
      liquid media at low and, more strongly, at high osmolality. Bacteria cultured at
      high osmolality without osmoprotectant were shorter and rounder than those
      cultured at low osmolality or with glycine betaine. Fluorescence microscopy
      showed that CL and ProP colocalize at the poles and near the septa of dividing E.
      coli cells. The polar localization of ProP was independent of its expression
      level but correlated with the proportion and polar localization of CL.
      Association with CL (and not PG) may be required for polar ProP localization.

PMID- 17504275
TI  - Good outcome in HIV-infected refugees after resettlement in New Zealand:
      population study.
AB  - BACKGROUND: The aims of this study were to determine the clinical characteristics
      on arrival and the subsequent clinical outcome of HIV-infected UN quota refugees
      who settled in New Zealand during the last 11 years and to estimate their rate of
      HIV transmission. METHODS: A population study was conducted. Data were provided
      by the Mangere Refugee Resettlement Centre, the infectious disease physicians
      caring for the subjects, the New Zealand AIDS Epidemiology Group and laboratories
      carrying out HIV viral load assays. RESULTS: One hundred of 7732 (1.3%) UN quota
      refugees were HIV positive; mean age 30 years, 56% were men, median initial CD4
      count was 320 (range 20-1358). HIV infection was most commonly acquired by
      heterosexual intercourse (74%). The median follow up was 5.0 years (range 1 month
      to 9.7 years). Five died and 15 subjects had 16 AIDS-defining illnesses, most
      commonly tuberculosis (n = 10). Sixty subjects commenced highly active
      antiretroviral therapy of whom 36/59 (61%) had an undetectable HIV viral load
      after 1 year of treatment. None of the six children born to HIV-infected women in
      New Zealand were infected. There were two known cases of horizontal transmission
      of HIV infection. CONCLUSION: Although HIV-infected quota refugees often have to
      overcome severe social, cultural and financial handicaps, their clinical outcome
      is generally very good, with response rates to highly active antiretroviral
      therapy that are similar to other patient groups. Furthermore, they have not been
      a significant source of transmission of HIV infection after resettlement in New
      Zealand.

PMID- 17504276
TI  - Engineering a safe landing: engaging medical practitioners in a systems approach
      to patient safety.
AB  - BACKGROUND: Several event studies, including the Australian Safety and Quality in
      Healthcare Study, emphasize gaps in safety for hospitalized patients. It is now
      recognized that system-based factors contribute significantly to risk of adverse
      events and this has led to a shift in focus of patient safety from the autonomous
      responsibility of medical clinicians to a systems-based approach. The aim of this
      study was to determine medical practitioner awareness of, level of engagement in
      and barriers to engagement in a systems approach to patient safety and quality.
      METHODS: Information from acute and subacute care medical practitioners at a
      metropolitan public hospital was collected within an anonymous structured
      electronic survey, a discussion group and key informant interviews. RESULTS:
      There were 73 survey respondents (response rate 7.6%). Fifty-one (69.9%) were
      unaware of the Institute of Medicine report 'To Err is human'. Thirty-six (49.3%)
      were unaware of the Australian Quality in Healthcare Study and 12 (16.4%) had
      read the article. There was a positive relation identified between awareness and
      seniority. There was a low level of participation in systems-focused quality and
      safety activities and limited understanding of the role of systems in medical
      error causation. There was uncertainty about the changing role of medical
      practitioners in patient safety and perceived lack of skills to effectively
      engage with hospital management about safety and quality issues. CONCLUSION:
      Several factors are limiting engagement of medical practitioners in a systems
      approach to patient safety. Increased educational support is needed and may be
      best focused within clinical effectiveness activities pertinent to practitioner
      interest and expertise.

PMID- 17504277
TI  - Thyrotoxic, hypokalaemic periodic paralysis: Polynesians, an ethnic group at
      risk.
AB  - BACKGROUND: Thyrotoxic, hypokalaemic periodic paralysis (TPP) is a reversible
      cause of severe muscle weakness that occurs in a small minority of thyrotoxic
      patients. Most cases to date have been reported in Asian men. AIMS: To evaluate
      the ethnic distribution of patients with TPP. METHODS: Retrospective analysis of
      all patients presenting with thyrotoxicosis and hypokalaemia with paralysis to
      two New Zealand hospitals. RESULTS: Seventy-one per cent of the 21 patients with
      TPP were of Polynesian ethnicity (Maori and Pacific Islander), 24% Asian and 5%
      European. Based on population demographics, these figures suggest a 37-fold
      overrepresentation for Polynesians and 159-fold for Asians compared with New
      Zealand Europeans. CONCLUSION: Polynesian, in addition to Asian people, are two
      ethnic groups at particular risk of TPP, and this condition must be considered in
      the differential diagnosis for patients presenting to the emergency department
      with severe hypokalaemia and weakness.

PMID- 17504278
TI  - How intravenous immunoglobulin is used in clinical practice: audits of two Sydney
      teaching hospitals.
AB  - BACKGROUND: The clinical demand for i.v. immunoglobulin (IVIg) continues to
      increase in Australia for reasons that are not clear. IVIg is distributed for
      approved indications according to Australian Health Ministers' Advisory Council
      2000 guidelines that are currently under review. IVIg may also be purchased by
      hospitals for uses not covered by these indications on an individual patient use
      basis. These audits were developed to examine current hospital practice in IVIg
      use. METHODS: Six-month prospective audits of all IVIg use were conducted at two
      teaching hospitals in Sydney (Concord and Royal Prince Alfred Hospitals). Medical
      files and dispensing records were examined and compared with current guidelines.
      RESULTS: One hundred and sixty-five recipients received 24,251 g of IVIg (mean
      total use 147 g/patient) for 36 distinct diagnoses, with 5.5% mortality. Drug
      committees supplied 1580 g of IVIg (6.5% of total product issued) to 12
      recipients (7.3% of total recipients). The clinical specialties of immunology,
      haematology and neurology accounted for 92.9% of IVIg use, with 51.8% of overall
      use for replacement indications. Forty-two patients (25.5%) received IVIg for non
      category 1 indications (4718 g, 19.5% of total product). Patients receiving IVIg
      for category 1 disorders had a 94.4% compliance with the guideline prerequisites
      where data were sufficient for assessment. DISCUSSION: Our findings show a
      greater than expected proportion of non-category 1 IVIg use and substantial
      contributions from drug committees. Careful case selection within category 1
      indications is evident in the high level of compliance with qualifying criteria.
      Current distribution procedures do not enable capture of outcome data to inform
      guideline revisions. CONCLUSION: These audits emphasize the requirement for
      updated National Clinical Practice Guidelines, improved approval procedures,
      consensus statements in the specialties of immunology, haematology and neurology
      and clarification of the role of drug committees.

PMID- 17504279
TI  - Audit of the care of the dying in a network of hospitals and institutions in
      Queensland.
AB  - BACKGROUND: Most Australians die in institutions and there is evidence to suggest
      that the care of these patients is not always optimal. Care pathways for the
      dying have been designed to transfer benchmarked hospice care to other settings
      (e.g. acute hospitals and residential age-care facilities) by defining goals of
      best care, providing guidelines to provide that care and documenting outcome.
      METHOD: A retrospective audit was undertaken across a network of health-care
      institutions in Queensland. The 18 goals considered essential for the care of the
      dying within the Liverpool Care Pathway were taken as a benchmark. Documentation
      of achievement of each of these goals was sought. RESULTS: The notes of 160
      patients who had died in eight institutions (four hospitals, three hospices, one
      nursing home) were reviewed. Several areas for improvement were identified,
      particularly in those goals relating to communication, resuscitation orders and
      care after death. Few units documented the provision of written information to
      families. Most patients were prescribed medications in anticipation of pain and
      agitation but less were prescribed drugs for other common symptoms in the dying.
      Most of the goals were achieved in a higher percentage of cases in hospice units.
      Marked differences in practice were noted between different institutions.
      CONCLUSION: The audit identified several aspects in the care of the terminally
      ill that could be improved. End-stage pathways may provide a model for improving
      the care of patients dying in hospitals and institutions in Australia.

PMID- 17504280
TI  - Circuit breakers for addiction.
AB  - The phenomenon of addiction is complex, although its expression clinically is
      relatively straightforward. There is a series of neurophysiological changes that
      mediate changes in the mesolimbic and mesocortical systems which in turn lead to
      disturbances in reward mechanisms. These then act to perpetuate the cycle of
      intoxication and reinforcement, withdrawal, craving and compulsive use. As our
      understanding of the pathophysiology of this process has improved, new
      pharmacological agents have been developed with the potential to moderate or even
      reverse it. This article briefly reviews the treatment of addiction with
      particular reference to emerging pharmaceutical agents.

PMID- 17504281
TI  - Severe intimal hyperplasia with ischaemic colitis in two patients with hepatitis
      C.
AB  - Many extrahepatic manifestations of hepatitis C have been described, including
      renal disease and vasculitis. We describe the novel finding of intimal
      hyperplasia associated with severe ischaemic events in two patients with
      hepatitis C. The combination of genotype 1a hepatitis C virus, rapidly
      progressive mesangiocapillary glomerulonephritis and intimal hyperplasia with
      ischaemic sequelae, may represent a new syndrome.

PMID- 17504282
TI  - Anti-CD20 antibody in thrombotic thrombocytopenic purpura refractory to plasma
      exchange.
AB  - Thrombotic thrombocytopenic purpura is a rare condition characterized by
      microangiopathic haemolytic anaemia, thrombocytopenia, altered neurology, renal
      impairment and fever. While plasma exchange has reduced mortality from more than
      90% to between 10 and 30%, a proportion of cases fail to respond. Rituximab may
      be efficacious in the management of refractory cases of thrombotic
      thrombocytopenic purpura. We present two cases in which rituximab was used with
      successful outcomes. Treatment resulted in resolution of severe clinical and
      haematological abnormalities in both patients. There has been no relapse after 16
      months follow up. Our experience supports the use of rituximab in difficult cases
      of TTP. Ongoing evaluation of its use is in progress at our institution.

PMID- 17504283
TI  - Is right heart thromboemboli another indication for thrombolysis?
AB  - Pulmonary embolism (PE) is a common and a potentially life-threatening disease.
      Diagnosis is challenging because the signs and symptoms are non-specific.
      Moreover treatment of PE is shrouded in controversy. Even at presentation the
      role of thrombolysis in managing patients with PE remains unclear. In those
      patients with right heart thromboemboli, thrombolysis is usually suggested, but
      the evidence remains unclear. We report a 34-year-old man who was diagnosed with
      right heart thromboemboli on echocardiography and was successfully managed with
      thrombolysis and anticoagulation. We also review the current published work on
      the management of patients with right heart thromboemboli.

PMID- 17504284
TI  - Road not taken: lessons to be learned from Queen v. Gillett.
AB  - Following the decision in the Gillet Case it may no longer be safe to rely on the
      Austroads guidelines when considering fitness to drive. This paper examines the
      case and its implications. Although the Guidelines claimed '... the
      identification and application of world best-practice...', they were disregarded
      by the court in Gillet. Both expert witnesses testified that on disclosure of
      epilepsy the accused would have been endorsed as fit for a licence application to
      the Roads & Traffic Authority, on the basis of 10 years of only nocturnal
      seizures, in accordance with the guidelines. The Court rejected this evidence and
      interpreted failure to disclose epilepsy as recognition of perceived risk and the
      previously undiagnosed sleep apnoea as the basis for that risk, despite being
      diagnosed after the accident. There needs to be greater certainty in the
      application of the guidelines, with legislative intervention and licenses should
      display a bold statement advising drivers of their responsibility to notify
      authorities of illnesses that could potentially affect driving.

PMID- 17504285
TI  - Intracranial bleed mimicking acute myocardial infarction.

PMID- 17504287
TI  - Spontaneous coronary artery dissection in an adolescent man with systemic lupus
      erythematosus.

PMID- 17504286
TI  - Expectoration of bronchogenic tumour tissue.

PMID- 17504288
TI  - Acute anaphylaxis following exercise stress testing.

PMID- 17504289
TI  - Two cases of severe liver injury possibly related to 5-fluorouracil and calcium
      folinate.

PMID- 17504290
TI  - Scuba diving, swimming and pulmonary oedema.

PMID- 17504291
TI  - No proof of cross-reactivity between celecoxib and antibiotic sulfonamides.

PMID- 17504292
TI  - Hazards of thrombolytic therapy for stroke: the real-world experience.

PMID- 17504294
TI  - Analysis of structure and patient thanks in scientific meeting oral
      presentations.

PMID- 17504295
TI  - Mutations in gastrointestinal stromal tumors--a population-based study from
      Northern Norway.
AB  - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the
      gastrointestinal tract. This tumor typically expresses KIT, and has KIT or PDGFRA
      activating mutation. In this study we evaluated 89 GISTs diagnosed in Northern
      Norway during a 30-year period. KIT exons 8, 9, 11, 13, and 17 were analyzed by
      PCR amplification and direct sequencing. Subsequently PDGRA exons 12, 14, and 18
      were evaluated in KIT wild-type cases. KIT mutations were found in 66 cases
      (75%), and PDGFRA mutations in 9 cases (10%). Most common were KIT exon 11
      mutations, with 58 cases. Tumors with Kit exon 11 point mutations had a
      significantly better prognosis than those with deletions. There were five KIT
      exon 9 duplications, three exon 13 point mutations, and one point mutation in
      exon 17. There were nine PDGFGRA mutations: seven in exon 18 and two in exon 12.
      All but one PDGFRA mutant GISTs were gastric tumors with epithelioid morphology,
      and these tumors were on average smaller than those with KIT mutations. KIT and
      PDGFRA wild type was found in 15% of cases. Analysis of KIT and PDGFRA mutations
      is of significance for treatment with tyrosine kinase inhibitors, and may also
      have value when assessing the biological potential of GIST.

PMID- 17504296
TI  - Changes of the Swedish Bordetella pertussis population in incidence peaks during
      an acellular pertussis vaccine period between 1997 and 2004.
AB  - In a surveillance programme undertaken from 1997 through 2004, Bordetella
      pertussis isolates and clinical information were collected after introduction of
      acellular pertussis vaccines (Pa) in 1996. Changes in the B. pertussis population
      were studied in three incidence peaks: 1999-2000, 2002 and 2004. Available
      isolates from 158 fully vaccinated children representing all of Sweden, plus 37
      from the Gothenburg area 2003-2004, were analysed by pulsed-field gel
      electrophoresis (PFGE), serotyping and sequencing of the virulence factor genes
      pertussis toxin subunits 1 and 3 (ptxA, ptxC), pertactin (prn), tracheal
      colonisation factor (tcfA) and fimbria3 (fim3). Allele ptxA1 was found in all
      isolates. There was a statistically significant increasing trend in three out of
      five studied genes, ptxC, prn and tcfA, and for a fourth, Fim3, if Gothenburg
      strains were included. The PFGE profile BpSR11 appearing in the 1999-2000 peak
      dominated by >or=23% during the entire period, bringing with it the allele
      combination 1/2/2/2/B (ptxA1/ptxC2/prn2/tcfA2/fim3B). Other BpSR11-related
      profiles with the same allele combination and more than 82% similarity--BpSR5 in
      the 2002 peak and BpSR12 in the 2004 peak--appeared with an increasing trend.
      Although vaccination with Pa has reduced disease, new variants have emerged
      representing clones surviving in the immunized population.

PMID- 17504297
TI  - Burkholderia cenocepacia, B. multivorans, B. ambifaria and B. vietnamiensis
      isolates from cystic fibrosis patients have different profiles of exoenzyme
      production.
AB  - Knowledge about the virulence mechanisms of species from the Burkholderia cepacia
      complex (BCC) is still limited. The genomovar heterogeneity and production of
      different virulence factors are likely to contribute to the variation in the
      clinical outcome observed in BCC-infected cystic fibrosis (CF) patients.
      Therefore, in this study we investigated the genetic polimorphism, the presence
      of genetic makers associated with virulence and transmissibility in BCC, and the
      profile of exoenzyme production of 59 BCC isolates obtained from 59 CF patients
      attending the reference CF centre in Rio de Janeiro, Brazil. The DNA sequence
      analyses of the recA gene allowed us to identify 40 of these 59 BCC species as
      being B. cenocepacia, 9 as B. vietnamiensis, 6 as B. multivorans and 4 as B.
      ambifaria. The assessment of the bacterial genetic polymorphism by PFGE revealed
      that B. cenocepacia and the B. multivorans isolates belonged to four and two
      different PFGE profiles with prevalence of two clones, A and B, respectively. All
      B. vietnamiensis and B. ambifaria belonged to only one PFGE profile (J and E,
      respectively). None of the isolates exhibited the genetic markers cblA and BCESM,
      assessed by polymerase chain reaction. In contrast, the profile of enzymatic
      activity, assessed by phenotypic methods, differed among the BCC species:
      protease activity was detected only in B. cenocepacia and B. ambifaria isolates,
      whereas only B. vietnamiensis isolates produced hemolysin. Although the
      phospholipase C activity was similar among the different species, the level of
      lipase activity produced by B. multivorans was higher than in the other species.
      We speculate that the differential characteristics of exoenzyme production may
      account for the differences in the pathogenic potentials of each BCC species.

PMID- 17504298
TI  - Secretagogin expression in tumours of the human brain and its coverings.
AB  - Secretagogin is a recently described calcium-binding protein, which is expressed
      in some neurons of the human brain. In this study we systematically investigated
      secretagogin expression in 245 tumours of the human brain and its coverings using
      immunohistochemistry. We found focal or widespread secretagogin expression in
      tumour cells in 1/18 oligoastrocytomas, 1/19 oligodendrogliomas, 2/20 anaplastic
      oligodendrogliomas, 2/9 ependymomas, 2/11 anaplastic ependymomas, 2/10
      glioblastomas, 3/11 gangliogliomas and 1/2 anaplastic gangliogliomas, 10/10
      central neurocytomas, 5/10 classic medulloblastomas, 4/5 desmoplastic
      medulloblastomas, 3/5 large cell/anaplastic medulloblastomas, 3/5 neuroblastomas,
      3/10 meningiomas, 2/10 haemangioblastomas, and 13/19 pituitary adenomas. Further,
      we observed secretagogin expression in endothelial cells in 5/10 meningiomas, 2/5
      haemangiopericytomas, and 2/10 haemangioblastomas. We detected no secretagogin
      expression in fibrillary astrocytoma, pilocytic astrocytoma, DNT, pineocytoma,
      pineoblastoma, subependymal giant cell astrocytoma (SEGA), atypical
      teratoid/rhabdoid tumour (AT/RT), or primary central nervous system lymphoma
      (PCNSL). We conclude that secretagogin is differentially expressed in human
      neuronal, glial, and embryonal brain tumours, meningial neoplasms and pituitary
      adenomas. Our findings indicate that secretagogin is involved in the calcium
      metabolism of tumour cells and endothelial cells in a subset of neoplasms of the
      brain and its coverings. Anti-secretagogin immunohistochemistry does not seem to
      be helpful in most differential diagnostic situations in surgical neuropathology.

PMID- 17504299
TI  - E-cadherin, beta-catenin, invasion and lymph node metastases in canine malignant
      mammary tumours.
AB  - Recent studies of canine malignant mammary tumours suggest that reduction of E
      cadherin and/or beta-catenin correlates with invasive behaviour and lymph node
      metastasis. The aims of this study were to examine the interrelationships between
      the expression of E-cadherin and beta-catenin, and the relationship between the
      expression of E-cadherin and/or beta-catenin and the mode of growth and
      metastatic capacity of canine malignant mammary tumours. 90 spontaneous malignant
      tumours and local and regional lymph nodes were studied. A significant
      relationship was evidenced between membranous expression of E-cadherin and beta
      catenin (p=0.0027), but not between E-cadherin and cytoplasmic beta-catenin. Only
      E-cadherin as a separate factor was significantly related to tumour invasion
      (p=0.0072) and lymph node metastasis (p=0.0001). Neither membranous nor
      cytoplasmic beta-catenin expression was significantly related to either of these
      phenomena.

PMID- 17504300
TI  - Antibacterial effects of home-made resin salve from Norway spruce (Picea abies).
AB  - Resin salve made from Norway spruce (Picea abies) is traditionally used in folk
      medicine to heal skin ulcers and infected wounds. Its antimicrobial properties
      were studied against certain human bacteria important in infected skin wounds.
      The sensitivity of the resin against Gram-positive and Gram-negative bacteria was
      studied in vitro by methods that are routinely used in microbiology laboratories.
      The resin salve exhibited a bacteriostatic effect against all tested Gram
      positive bacteria but only against Proteus vulgaris of the Gram-negative
      bacteria. Interestingly, the resin inhibited the growth of bacteria, including
      methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
      enterococcus (VRE), both on agar plates and in culture media. The study
      demonstrated antimicrobial activity of the resin salve and provided objective
      evidence of its antimicrobial properties. It gives some explanations why the
      traditional use of home-made resin salve from Norway spruce is experienced as
      being effective in the treatment of infected skin ulcers.

PMID- 17504301
TI  - Absence of nucleophosmin 1 (NPM1) gene mutations in common solid cancers.
AB  - Nucleophosmin is a nucleolar phosphoprotein that shuttles between nucleus and
      cytoplasm. Recent reports demonstrated that exon 12 of the nucleophosmin 1 (NPM1)
      gene was frequently mutated in acute myelogenous leukemias (AMLs). To see whether
      the NPM1 mutation occurs in other malignancies, we analyzed exon 12 of NPM1 for
      the detection of somatic mutations in 467 carcinomas, including 142 lung, 47
      hepatocellular, 93 breast, 103 colorectal and 82 gastric carcinomas, by single
      strand conformation polymorphism assay. We also analyzed the NPM1 mutation in 142
      acute leukemias, including 105 AMLs. We detected 15 NPM1 mutations in the AMLs
      (14.3%), but there was no NPM1 mutation in the other malignancies analyzed. Our
      data indicate that NPM1 exon 12 is mutated in AMLs, but not in other common human
      cancers, and suggest that the NPM1 mutation may not play a role in the
      tumorigenesis of common solid cancers.

PMID- 17504302
TI  - Application of fluorescent in situ hybridisation for demonstration of Coxiella
      burnetii in placentas from ruminant abortions.
AB  - A fluorescent in situ hybridisation (FISH) assay targeting 16S ribosomal RNA was
      developed for detection of the zoonotic bacterium Coxiella burnetii in formalin
      fixed, paraffin-embedded tissue, and applied on placentas from ruminant
      abortions. The applicability of the FISH assay was compared to
      immunohistochemistry (IHC) using human positive control serum in 12 cases of C.
      burnetii-associated placentitis as well as 7 negative control tissue samples. In
      all 12 cases the bacterium was detected within trophoblasts as well as free in
      the placental debris by both FISH and IHC. Extensive and significant infection by
      C. burnetii was revealed in 10 of the cases, whereas a slighter and focal
      distribution of the bacterium was observed in two cases. 90 aborted placentas
      from Danish ruminants were investigated by FISH. C. burnetii was detected in one
      bovine case only, representing the first confirmation of C. burnetii in Danish
      animals. The study shows that FISH targeting 16S ribosomal RNA is a feasible
      diagnostic tool for detection of C. burnetii in tissue samples and fully
      comparable to IHC.

PMID- 17504303
TI  - Expression of phosphorylated caspase-9 in gastric carcinomas.
AB  - Alterations of caspases, the main executioners of apoptosis, have been described
      in human cancers. Caspase-9 plays a crucial role in the initiation phase of the
      intrinsic apoptosis pathway. Caspase-9 is phosphorylated at Thr125 through the
      mitogen-activated protein kinase (MAPK) pathway, and this phosphorylation is
      associated with inhibition of caspase-9 activation. The aim of this study was to
      explore whether phosphorylated caspase-9 (p-caspase-9) expression could be a
      characteristic of gastric carcinomas. We analyzed expression of p-caspase-9
      protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue
      microarray approach. p-caspase-9 was detected in 33 of the 60 carcinomas (55%).
      Both early and advanced gastric carcinomas expressed p-caspase-9. There was no
      significant association of p-caspase-9 expression with clinocopathological
      characteristics, including invasion, metastasis and stage. In contrast to gastric
      cancer cells, epithelial cells in normal gastric mucosa showed no or only weak
      expression of p-caspase-9. Taken together, these results indicate that caspase-9
      is frequently phosphorylated in gastric carcinomas, and that the phosphorylation
      of caspase-9 might be an inhibitory mechanism of caspase-9-mediated apoptosis in
      gastric carcinomas. Increased expression of p-caspase-9 in malignant gastric
      epithelial cells compared to normal mucosal epithelial cells suggests that p
      caspase-9 expression might play a role in gastric carcinoma development.

PMID- 17504304
TI  - Impact of an increase in grading categories and double reporting on the
      reliability of breast cancer grade.
AB  - The present study illustrates the effect of using the consolidated total score
      (obtained on a 7-point scale by adding the tubular, nuclear and mitotic scores)
      as well as double reporting on the interobserver reliability of breast cancer
      grading by the Nottingham method. 50 consecutive breast cancer slides were graded
      independently by 5 pathologists. The interobserver reliability between the
      individual pathologists for final grade, total score and grade components was
      estimated by quadratic weighted kappa (k(w)). Similarly, the inter-observer
      reliability of double reported scores (obtained by averaging the reported scores
      of two independent pathologists) for independent observer pairs was estimated.
      The total scores gave higher reliability figures than the final grade both for
      individual pathologists and double reported scores. The double reported total
      scores and grade also gave significantly higher reliability figures than the
      individual scores and grade (average k(w)=0.65 and 0.78 for the individual and
      double reported total scores, respectively; 0.61 and 0.66 for the individual and
      double reported grades).Therefore, use of total scores in addition to grade as
      well as double reporting of the same significantly increases the interobserver
      reliability of breast cancer grading.

PMID- 17504305
TI  - Malignant phyllodes tumor with associated osteosarcomatous, chondrosarcomatous,
      and liposarcomatous overgrowth.

PMID- 17504306
TI  - An Asian variant of intravascular lymphoma: unique clinical and pathological
      manifestation in the gallbladder.
AB  - We here present a rare case of intravascular lymphoma (IVL) in a Japanese man. 4
      months after cholecystectomy due to cholecystitis, a diagnosis of intravascular
      lymphoma (IVL) was strongly suspected. Lymphoma cells were diffusely observed in
      the bone marrow parenchyma, but were absent in the vascular spaces. The patient
      died of respiratory failure and at autopsy a small number of lymphoma cells in
      the extravascular parenchyma of the adrenal gland and bone marrow were seen.
      Serial sections of the surgically resected gallbladder retrospectively confirmed
      the diagnosis of IVL. In addition, congestion and edema were observed in the
      connective tissue layer. It is possible that edema or ischemia in the gallbladder
      wall or at other anatomic sites due to the circulation disturbance induced by the
      intravascular obstruction of lymphoma cells may have caused the initial symptoms.
      In conclusion, clinicians and pathologists should keep in mind that the
      gallbladder may be initially involved in IVL.

PMID- 17504307
TI  - Primary malignant myoepithelioma of the distal femur.
AB  - A 55-year-old male presented with a 1-month history of localized pain caused by
      an osteolytic and destructive lesion in the right distal femur. Histologically,
      the tumour consisted of spindle cells intermingled with epithelioid eosinophilic
      cells arranged in small cords embedded in a hyalinized-to-chondromyxoid stroma.
      Electron microscopy and immunohistochemistry showed features of myoepithelial
      differentiation. RT-PCR failed to demonstrate chimeric transcripts of
      extraskeletal myxoid chondrosarcoma. The final diagnosis was primary malignant
      myoepithelioma of bone. The patient is alive with lung metastases 13 months after
      surgery. Primary malignant myoepithelioma of bone is an exceptionally rare
      neoplasm that should be considered in the differential diagnosis with the more
      aggressive myxoid spindle cell sarcomas.

PMID- 17504308
TI  - Spontaneous rupture of a benign giant adrenal adenoma.
AB  - We report on a 50-year-old patient with a giant benign adenoma of the adrenal
      cortex, which ruptured spontaneously, leading to life-threatening retroperitoneal
      hemorrhage. Following emergency adrenalectomy with sparing of the ipsilateral
      kidney, an adenoma of the adrenal cortex with a diameter of 18 cm and a weight of
      1400 g was found. A detailed literature search showed this to be the largest
      benign tumor of the adrenal cortex described so far. We discuss the diagnosis and
      treatment of this unusual tumor.

PMID- 17504309
TI  - Radiological manifestations of the skeleton, lungs and brain in Stueve-Wiedemann
      syndrome.
AB  - A total of 25 patients with the rare skeletal dysplasia Stueve-Wiedemann syndrome
      (SWS) have been evaluated during the last 11 years. Of all patients with clinical
      suspicion of SWS, skeletal and chest radiographs were obtained for classification
      of the underlying skeletal dysplasia. In one case, CT was carried out for the
      first time for further investigation of the midface hypoplasia. Typical
      conventional radiological findings and CT features were analysed and compared
      with published data. Early diagnosis of SWS was made by correlating radiological
      and clinical findings. Follow-up radiological examinations of the skeleton and of
      the chest were carried out in six children surviving infancy for evaluation of
      progression. Clinically, they suffered from progressive orthopaedic problems,
      recurrent aspiration pneumonia and recurrent episodes of hyperthermia, as well as
      cutaneous infections. Radiologically progressive bowing of the long tubular bones
      and progressive metaphyseal decalcification were present on follow-up skeletal
      radiographs. Skeletal abnormalities in SWS are so characteristic that an early
      post-partum diagnosis can be made by correlation of typical clinical and
      radiological findings. Few cases survive infancy. First, these patients face
      progressive orthopaedic problems and respiratory infections.

PMID- 17504310
TI  - CT scout view as an essential part of CT reading.
AB  - Computed tomography scout view is a mode of operating a CT system. It is
      generally used to prescribe CT slices and to display slice locations rather than
      for direct diagnosis. However, we found that a careful study of CT scout view can
      contribute significantly to the diagnosis. We show seven abdominal, two chest and
      two head CT, where the study of CT scout view allowed diagnoses to be made that
      were not readily apparent from the axial slices.

PMID- 17504311
TI  - Literature review and suggested protocol for managing ultrasound soft markers for
      Down syndrome: thickened nuchal fold, echogenic bowel, shortened femur, shortened
      humerus, pyelectasis and absent or hypoplastic nasal bone.
AB  - Mid-trimester soft markers have been linked with Down syndrome and other
      aneuploidies. There are many other prenatal screening tests available with better
      detection rates for Down syndrome than the mid-trimester ultrasound. Many
      patients confronted with the diagnosis of a soft marker become anxious and may
      request a diagnostic test (amniocentesis) despite the associated risk of
      miscarriage. This is also despite the fact that most fetuses with an isolated
      soft marker are chromosomally normal. The management of a pregnancy with a soft
      marker must therefore be planned in a manner designed to minimize patient
      anxiety. Likelihood ratios can be used to modify a patient's 'prior risk' (based
      on age or prior screening tests) and create a new risk. This calculation may help
      identify a subset of patients suitable for further investigation. It has been
      proposed that 'negative' likelihood ratios can be used to reduce a patient's risk
      if no soft marker is found at a mid-trimester ultrasound. There remain concerns
      about this approach and further research is required before this approach enters
      common practice. The published work surrounding the management of thickened
      nuchal fold, echogenic bowel, shortened femur, shortened humerus, pyelectasis
      (renal pelvis dilatation) and hypoplastic nasal bone is reviewed. Each soft
      marker has different associations and individual management plans for each of
      these soft markers are presented. Although isolated single umbilical artery is
      not usually considered a soft marker of aneuploidy, a management plan for this
      common finding is also included.

PMID- 17504312
TI  - Diagnostic accuracy of shoulder ultrasound performed by a single operator.
AB  - Both diagnostic ultrasound and magnetic resonance imaging (MRI) are used for
      investigation of the presence and severity of rotator cuff lesions. There is no
      consensus as to which is the more accurate and cost-effective study. We sought to
      examine the sensitivity of ultrasound, when used by one experienced radiologist
      with modern equipment. We compared the ultrasound and surgical results obtained
      from 68 patients. Ultrasound showed a sensitivity of 89% and specificity of 100%
      (Positive Predictive Value 100%) for full-thickness tears, and a sensitivity of
      79% and specificity of 94% (Positive Predictive Value 87%) for partial-thickness
      tears. We found that shoulder ultrasound, in the hands of an experienced
      radiologist with the use of modern high-resolution equipment, is highly sensitive
      in differentiating complete tears and partial-thickness tears. Our results are
      similar to the best published results for MRI and given that ultrasound is
      significantly cheaper and more available, ultrasound by an experienced
      radiologist should be considered as a primary diagnostic tool for imaging the
      rotator cuff.

PMID- 17504313
TI  - Colour Doppler ultrasound evaluation of orbital vessels in diabetic retinopathy.
AB  - The aim of this study was to determine the role of colour Doppler imaging in the
      retrobulbar vascular circulation in diabetic retinopathy (DR). Maximum (V(max)),
      end-diastolic (V(min)) and average (V(mean)) velocities of blood flows and
      pulsatility index and resistivity index (RI) in central retinal artery (CRA),
      short branches of posterior ciliary artery (PCA) and ophthalmic artery of the 65
      diabetic and 22 control eyes were measured. The CRA V(max) level in the control
      group was significantly higher than in DR groups. The CRA V(mean) level was also
      significantly higher in the control group than in the mild nonproliferative
      diabetic retinopathy (NPDR) and the moderate NPDR groups. The CRA RI value was
      significantly higher in the control group than in the nonretinopathy group. The
      CRA V(min) and the ophthalmic artery RI values were found significantly higher in
      the nonretinopathy group than in the moderate NPDR group. There were significant
      decreases in the some CRA and PCA values as glycated haemoglobin (HbA1c) levels
      increase in diabetic group. There was a positive correlation between the duration
      of diabetes and HbA1c levels. This study showed the presence of some dynamic
      circulatory alterations in the nonretinopathy group with diabetes and DR groups.
      It was also shown that there is a negative correlation between HbA1c and some
      orbital vascular velocities.

PMID- 17504314
TI  - CT evaluation of congenital choanal atresia: our experience and review of the
      literature.
AB  - Congenital choanal atresia (CCA) is the developmental failure of the nasal cavity
      to communicate with the nasopharynx. The aim of this study was to investigate and
      analyse the CT findings in such cases. Seven patients with CCA were included in
      our study over a 3-year period (2001-2004). All had a CT scan of the nasal cavity
      and nasopharynx to establish the diagnosis and to define the extent and type of
      atresia. The choanal atresia was found to be more commonly bilateral and more of
      the mixed (membranous-osseous) type. Bilateral CCA in the neonate is a medical
      emergency that should be treated as early as possible. Computed tomography is a
      valuable and easily accessible diagnostic tool.

PMID- 17504315
TI  - Ultrasound imaging features of radial scars of the breast.
AB  - Radial scars of the breast are common benign lesions, which are often
      radiologically occult. When they are detected by imaging, they are most often
      found by mammography. Radial scars are usually impalpable and have traditionally
      been localized for core biopsy and hookwire placement preoperatively by
      mammographic guidance. Stereotactic biopsy and localization is often difficult.
      Ultrasound-guided core biopsies and hookwire placement have the potential to
      provide a more accurate needle placement. The aim of this study was to determine
      the proportion of radial scars detectable by ultrasound and the feasibility of
      carrying out core biopsies and hookwire localization ultrasonographically. A
      retrospective review of the records of 7236 women was undertaken to determine
      those who had a histological diagnosis of radial scar. A total of 44 radial scars
      in 43 women were found, of which 40 had images that were available for analysis.
      Sixty-eight per cent of radial scars are visible on ultrasound, most commonly
      seen as hypoechoic areas/masses. Parenchymal distortion without a hypoechoic mass
      was seen in 22%. In 8%, the lesion was appreciably better visualized by
      ultrasound when compared with mammography. In one case, the lesion was detected
      on ultrasound and not detected by mammography. At least two-thirds of
      mammographically detected radial scars can be visualized on ultrasound. These
      should be submitted to preoperative core biopsy and hookwire localization under
      ultrasound control.

PMID- 17504316
TI  - Uterine artery embolization for symptomatic fibroids with imaging follow up.
AB  - The aim of this study was to determine the effectiveness of uterine artery
      embolization (UAE) as a primary treatment method in treatment of symptomatic
      fibroids, whether there are any preembolization MRI characteristics of fibroid
      predictive of reduction in volume and assess reduction in uterine and dominant
      fibroid volumes using ultrasound (US) and MRI. Study was carried out in total of
      32 patients aged 25-49 years (mean 40.9 years). Uterine and dominant fibroid
      volume were determined using US and MRI before UAE, MRI and US at 3 months and US
      alone at 6 and 12 months post-UAE, supplemented by clinical evaluation at
      interval of 3, 6 and 12 months. Procedure was carried out through unilateral
      femoral puncture using poly vinyl alcohol (PVA) particles 355-500 microm in size.
      All 32 patients had successful procedures. Overall, 25 patients responded, giving
      a clinical success rate of 78.12%. Mean reduction in volume of uterus and fibroid
      was 33 and 59.7% and 48.9 and 75.5% on US at 3 and 12 months respectively, and
      33.3 and 58.6% on MRI at 3 months. Volume reduction on US and MRI at 3 months was
      highly correlative. There was no statistical difference in size reduction in
      volume of fibroids, which were hypointense or hyperintense on T2-weighted image
      (T2WI) on pre-UAE MRI. Uterine artery embolization leads to good technical
      success and fibroid volume reduction. Ultrasound alone may be used for follow up
      of patients post-UAE. Preprocedure signal characteristics on T2WI are not
      predictors of volume reduction after UAE.

PMID- 17504317
TI  - Normal measurement of orbital structures: implications for the assessment of
      Graves' ophthalmopathy.
AB  - Compute tomography anatomy of the orbits is well described, but only a few
      reports are available on normal measurements of the extraocular muscles (EOM) and
      globe position (GP). We obtained CT images from patients who were referred to our
      department for CT of the paranasal sinuses using a standard protocol for
      evaluation of normal orbital measurements. Our study suggests that optimum
      results are attained with the use of a coronal scan at a window level and width
      setting that results in an optimum image at the maximum muscle width for
      assessment of EOM and an axial scan at the mid-GP for GP and interzygomatic line.
      Based on our normal values, a right-to-left ratio of more than 1.4 for EOM
      diameter or 1.2 for GP is indicative of asymmetry. An absolute diameter of EOM >
      8 mm and GP < 2 mm are abnormal.

PMID- 17504318
TI  - MR shoulder arthrography in patients younger than 40 years of age: frequency of
      rotator cuff tear versus labroligamentous pathology.
AB  - The purpose of this study was to compare the frequency of rotator cuff pathology
      versus labroligamentous pathology in patients younger than 40 years and to
      determine whether routine MR arthrography is justified in all patients in this
      age group, regardless of the clinical symptoms. The MR arthrography was carried
      out on 332 patients 40 years of age and younger. Two hundred and forty-three
      patients had clinical history of instability and possible labroligamentous
      pathology. Eighty-nine patients had no history or physical signs of instability
      and were referred for reasons other than instability, such as assessment for
      rotator cuff tear. In the 243 patients younger than 40 years with clinical
      history of potential labral pathology, 39% (95/243) showed a labral tear and 2.1%
      (5/243) had a full-thickness rotator cuff tendon tear. In the 89 patients with no
      history suggesting labral pathology, 19% (17/89) showed an unsuspected labral
      tear and 4.5% (4/89) had a full-thickness rotator cuff tear. These findings
      suggest that, regardless of the clinical indication for referral, patients aged
      40 and less referred for shoulder MRI should be imaged using MR arthrography
      because of the significant risk that symptoms are related to unsuspected labral
      pathology.

PMID- 17504319
TI  - The ability of ultrasound to detect gynaecological neoplasms and their ultrasound
      morphological features.
AB  - To determine first, the accuracy of a gynaecological ultrasound service in the
      detection of four clinically significant pathologies, namely, uterine body
      malignancy, ovarian malignancy, ovarian dermoid cysts and other benign ovarian
      pathologies and second, to review the ultrasound imaging appearances of ovarian
      masses with histopathological correlation. Retrospective data collection from
      consecutive weekly multidisciplinary team meetings over a 12-month period. All
      patients had undergone ultrasound examination before surgery. Data included
      patient demographics, menopausal status, indications for ultrasound, type of
      practitioner carrying out the scan, operative findings and final
      histopathological diagnosis. Ultrasound imaging appearances were correlated to
      histology. Of the 47 cases of uterine malignancy, 45 had endometrial carcinoma.
      All had either a thickened or poorly seen or not seen endometrium. Twenty-four
      per cent of these women were premenopausal. Forty-seven of the 48 cases of
      ovarian malignancy had abnormal ultrasound findings. In six of these, the
      findings were of a purely cystic lesion. There were 62 cases of benign ovarian
      pathology (excluding dermoid cyst), all of which had an abnormal ultrasound; 16
      of these had possible ultrasound features of malignancy. All 30 cases of ovarian
      dermoid cyst had an abnormal ultrasound with a specific diagnosis being made in
      27. This study shows that ultrasound is accurate in the detection of both
      endometrial and ovarian disease. The endometrium that is not seen or is poorly
      seen is an indication for endometrial biopsy in women with postmenopausal
      bleeding. There is considerable overlap in the ultrasound appearances of benign
      and malignant ovarian lesions. Ultrasound is a good method for the accurate and
      specific diagnosis of an ovarian dermoid cyst.

PMID- 17504320
TI  - Technique for axillary radiotherapy using computer-assisted planning for high
      risk skin cancer.
AB  - High-risk skin cancer arising on the upper limb or trunk can cause axillary nodal
      metastases. Previous studies have shown that axillary radiotherapy improves
      regional control. There is little published work on technique. Technique
      standardization is important in quality assurance and comparison of results
      especially for trials. Our technique, planned with CT assistance, is presented.
      To assess efficacy, an audit of patients treated in our institution over a 15
      month period was conducted. Of 24 patients treated, 13 were treated with radical
      intent, 11 with this technique. With a follow up of over 2 years, the technique
      had more than a 90% (10/11) regional control in this radical group. Both of the
      radical patients who were not treated according to the technique had regional
      failure. One case of late toxicity was found, of asymptomatic lymphoedema in a
      radically treated patient. This technique for axillary radiotherapy for regional
      control of skin cancer is acceptable in terms of disease control and toxicity as
      validated by audit at 2 years.

PMID- 17504321
TI  - Nasopharygeal carcinoma in Queensland, Australia: a review of 10 years
      experience.
AB  - The purpose of this study was to compare the treatment outcomes of patients with
      nasopharyngeal carcinoma in Queensland in a 10-year period during which
      synchronous chemoradiotherapy has come into use and to compare characteristics of
      patients of different racial origins and their prognostic factors. Eighty-one
      patients treated between 1991 and 2001 at the Queensland Radium Institute,
      Brisbane, Queensland for histologically confirmed nasopharyngeal carcinoma were
      included. Seventeen patients were treated using the Intergroup protocol, 32
      patients with miscellaneous synchronized chemoradiotherapy, 6 patients with
      neoadjuvant regimens and 26 patients with radiotherapy only. Asian patients were
      found to present earlier than White Australian patients (P < 0.02). No
      significant difference was identified in the histological presentation between
      the two ethnic groups. Asian patients were more likely to have a relapse and poor
      loco-regional control. Overall survival, however, was not different. Patients
      treated according to the Intergroup protocol had better disease-specific survival
      and relapse-free survival than the other groups. The median follow up was 36
      months. Twenty-five patients (30%) developed recurrent disease. The 5-year
      salvage survival or survival after relapse was 15%. Our experience with the
      Intergroup protocol in our population is similar to other studies, with
      likelihood of improved results.

PMID- 17504322
TI  - Differences in toxicity across gender in patients treated with chemoradiation for
      rectal cancer.
AB  - The primary objective was to prospectively investigate the efficacy and toxicity
      of bolus 5-fluorouracil (5-FU) chemotherapy compared with the infusional 5-FU in
      combination with preoperative radiation in patients with locally advanced rectal
      cancer. Furthermore, in light of previous reports, toxicity profiles between men
      and women were also compared. Eighty-four consecutive patients with rectal
      adenocarcinoma were prospectively treated. There were no differences in tumour
      response, local recurrence or survival between bolus versus infusional groups or
      gender groups. In locally advanced rectal cancer, preoperative infusional
      chemotherapy combined with radiation was found to be less toxic than bolus
      chemotherapy and radiotherapy. Both regimens produced more toxic effects in women
      compared with men.

PMID- 17504323
TI  - CT planning for breast cancer.
AB  - Radiotherapy to the affected breast or chest wall is well established as an
      integral part of postoperative management of breast cancer. However, it is known
      to be associated with increased cardiac and pulmonary morbidities and
      mortalities. Modern technologies, such as CT planning, have shown to improve
      treatment planning by accurately delivering optimal doses to the target volumes,
      while minimizing doses to sensitive structures, thus reducing potential treatment
      related adverse effects. The purpose of this study is to report on our
      experiences with CT planning of adjuvant radiotherapy for breast cancer.

PMID- 17504324
TI  - Re: Radiation oncology clinical audit: a matter of behaviour and performance.

PMID- 17504325
TI  - Re: Radiation: facts, fallacies and phobias.

PMID- 17504326
TI  - Nephrogenic systemic fibrosis associated with gadolinium-containing contrast
      media administration in patients with reduced glomerular filtration rate.

PMID- 17504334
TI  - Should ileal pouch-anal anastomosis include mucosectomy?
AB  - OBJECTIVE: Debate exists as to the benefits of performing mucosectomy as part of
      pouch surgery for ulcerative colitis (UC) and familial adenomatous polyposis
      (FAP). Whilst mucosectomy results in a more complete removal of diseased mucosa,
      this benefit may be at the price of poorer function. We examined these issues.
      METHOD: Using Medline, Embase, Ovid and Cochrane database searches papers were
      identified relating to the outcome following pouch surgery with and without
      mucosectomy. Potential reasons for functional problems were investigated, as were
      rates of 'cuffitis', dysplasia, polyposis and cancer in the ileal pouch and anal
      canal. RESULTS: The available evidence suggests that performing a mucosectomy
      leads to a worse functional outcome. Meta-analysis suggested that nighttime
      seepage of stool and resting and squeeze pressure were worse after mucosectomy.
      The most likely reason for functional impairment following pouch surgery was the
      degree of anal manipulation. Mucosectomy does seem to confer benefit in terms of
      disease control but this benefit does not reach statistical significance.
      CONCLUSION: Stapled anastomosis avoiding mucosectomy is the approach of choice
      for ileal pouch anal anastomosis because this leads to superior functional
      outcome. Performing mucosectomy results in some clinical benefits in terms of
      lower rates of inflammation and dysplasia in the retained mucosa in UC patients
      and lower rates of cuff polyposis in FAP patients. However, on the basis of
      available evidence mucosectomy is only indicated in those cases where the patient
      is at a high risk of disease in the retained rectal cuff.

PMID- 17504335
TI  - Chemoprevention of colorectal cancer - a new target needed?
AB  - OBJECTIVE: Novel treatments for colorectal cancer (CRC) include chemoprevention.
      Nonsteroidal anti-inflammatory drugs (NSAIDs) were the first to be studied and an
      inverse association was proven between their use and the development of invasive
      CRC. The numerous side effects of NSAIDs led, however, to the search for safer
      drugs. These have included Coxibs (selective COX-2 inhibitors). In this study,
      the role of coxibs in the chemoprevention of CRC is reviewed. RESULTS: Numerous
      in-vitro and in-vivo experiments have shown the effectiveness of coxibs in the
      chemoprevention of CRC. These have led to the registration of celecoxib by the
      USA Food and Drug Administration for the treatment of familial adenomatous
      polyposis. Further studies of coxibs have revealed an increased risk of serious
      cardiovascular events when compared with placebo. This finding has considerably
      decreased the opportunities for chemoprevention of CRC. CONCLUSION: The multi
      directional activity of coxibs, which was the reason for their effectiveness
      against CRC development may be the key to proposing a new target area for
      chemoprevention. It has been shown that celecoxib partly inhibits the activity of
      NF-kappaB, transcription factor involved in inflammation and carcinogenesis
      pathways. Modulation of its activation may be the future of effective CRC
      chemoprevention.

PMID- 17504336
TI  - Diagnostic precision of magnetic resonance imaging for preoperative prediction of
      the circumferential margin involvement in patients with rectal cancer.
AB  - OBJECTIVE: Circumferential margin involvement (CMI) is an important prognostic
      indicator for patients with rectal cancer. This meta-analysis aims at evaluating
      the diagnostic precision of magnetic resonance imaging (MRI) for the preoperative
      evaluation of CMI in patients with rectal cancer. METHOD: Quantitative meta
      analysis was performed comparing MRI against histology after total mesorectal
      excision. Sensitivity, specificity and diagnostic odds ratio (DOR) were
      calculated for each study. Summary receiver operating characteristic (SROC)
      curves and subgroup analysis were undertaken. Study quality and heterogeneity
      were evaluated. Meta-regression meta-analysis was used to evaluate the
      significance of the difference in relative DORs. RESULTS: Nine studies evaluating
      529 patients were included. Pooled results showed an overall sensitivity and
      specificity for MRI detecting CMI preoperatively of 94% and 85% respectively. The
      SROC analysis demonstrated an overall weighted area under the curve (AUC) of 0.92
      (DOR 57.21, 95% CI 18.21-179.77), without significant heterogeneity between the
      studies (Q-value 14.66, P = 0.06). Good study quality further increased the
      sensitivity and specificity of MRI. The use of a 1.5 Tesla coil, a phased array
      coil and the inclusion of two interpreters also resulted in high preoperative
      diagnostic precision. Meta-regression meta-analysis showed a significant
      difference in the DOR for studies published in or since 2003 (P = 0.019).
      CONCLUSION: Magnetic resonance imaging can accurately predict CMI preoperatively
      for rectal cancer in single units and this is reproducible across different
      centres. This strategy has important implications for selection of patients for
      adjuvant therapy prior to surgery.

PMID- 17504337
TI  - Magnetic resonance imaging for preoperative staging of rectal cancer in clinical
      practice: high accuracy in predicting circumferential margin with clinical
      benefit.
AB  - OBJECTIVE: The aims were to determine agreement between staging of rectal cancer
      made by magnetic resonance imaging (MRI) and histopathological examination and
      the influence of MRI on choice of radiotherapy (RT) and surgical procedure.
      METHOD: In this retrospective audit, preoperative MRI was performed on 91
      patients who underwent bowel resection, with 93% having total mesorectal
      excision. Tumour stage according to mural penetration, nodal status and
      circumferential resection margin (mCRM) involvement was assessed and compared
      with histopathology. RESULTS: Five radiologists interpreted the images. Overall
      agreement between MRI and histopathology for T stage was 66%. The greatest
      difficulty was in distinguishing between T1, T2 and minimal T3 tumours. The
      accuracy for mCRM (MRI) was 86% (78/91),with an interobserver variation between
      80% and 100%. In the 13 cases with no agreement between mCRM and pCRM
      (pathological), seven had long-term RT and nine en bloc resections, indicating
      that the margins initially were involved with an even higher accuracy for mCRM.
      Preoperative short-term RT was routine, but based on MRI findings, choice of RT
      was affected in 29 cases (32%); 17 patients had no RT and 12 long-term RT. The
      surgical procedure was affected in 17 cases (19%) with planned perirectal en bloc
      resections in all. CRM was involved (< or = 1 mm) in 14.7% of the 34 cases in
      which MRI had an effect upon choice of RT and/or surgery compared with 8.8% of
      the remaining 57 cases where it had no impact. CONCLUSION: Magnetic resonance
      imaging predicted CRM with high accuracy in rectal cancer. MRI could be used as a
      clinical guidance with high reliability as indicated by the low figures of
      histopathologically involved CRM.

PMID- 17504338
TI  - Following anterior resection for rectal cancer, defunctioning ileostomy closure
      may be significantly delayed by adjuvant chemotherapy: a retrospective study.
AB  - OBJECTIVE: A temporary loop ileostomy is often created to minimize the impact of
      peritoneal sepsis from an anastomotic dehiscence following colo-anal or low
      colorectal anastomosis. These stomas are not without complications. Clinicians
      tend to advise patients that their loop ileostomy will be reversed within 6-12
      weeks of formation. However, factors such as adjuvant chemotherapy may affect the
      timing of closure. The aim of this study was to review the time between formation
      and closure of loop ileostomies following total mesorectal excision in patients
      with rectal cancer. METHOD: A retrospective study of 50 patients with loop
      ileostomies to defunction total mesorectal excisions for rectal cancer, between
      April 2002 and July 2005. RESULTS: Of the 50 patients with defunctioning loop
      ileostomies, 24 received adjuvant chemo-radiotherapy, and 26 did not. There was a
      28% morbidity. The overall median time from formation to closure was 142 days (35
      575). Median time from formation to closure in those with adjuvant therapy was
      197 days (35-575) and in those with no adjuvant therapy was 133 days (75-395).
      This was a significant delay (P = 0.049). Sixteen stomas were not closed to date.
      CONCLUSION: Time between formation and closure of loop ileostomy following
      anterior resection of rectum is significantly delayed by adjuvant chemotherapy.
      Because of their high morbidity, defunctioning ileostomies should be closed as
      early as medically possible, especially if adjuvant chemotherapy is planned.

PMID- 17504339
TI  - A comparison of quality of life and postoperative results from combined PPH and
      conventional haemorrhoidectomy in different cases of haemorrhoidal disease.
AB  - OBJECTIVE: To compare the early postoperative results and late patient-related
      postoperative results by a Short-Form 36 quality of life survey after
      conventional haemorrhoidectomy and PPH procedure with additional surgical
      intervention in noncomplicated, complicated and delayed cases of the disease.
      METHOD: The comparison was made between comparable patient groups after
      conventional haemorrhoidectomy (n = 168) and after PPH with additional surgical
      intervention (n = 142). The early and late postoperative results and quality of
      life analysis according to SF-36 questionnaire were compared. RESULTS: The length
      of procedure was significantly shorter after the PPH procedure (37.4 vs 49.4
      min). The amount of postoperative nonopiate analgesics was similar, but
      consumption of opiates was more in the conventional group. The rate of early
      postoperative complications was similar. In the PPH group significant improvement
      in all quality of life parameters was ascertained 6 months after operation, but 6
      weeks after surgery several parameters in this group were lower. In the
      conventional group improvement was ascertained only for several parameters. The
      significant improvement of quality of life after PPH operations was ascertained
      especially at a mean period of 6 weeks. CONCLUSION: The PPH procedure performed
      in complex cases of the disease and combined with other surgical intervention
      because of the anorectal comorbidity assures better early postoperative results
      and better postoperative quality of life in a 6-month follow up in comparison
      with conventional haemorrhoidectomy. The continuation of quality of life studies
      with a longer follow up is required concerning Longo operation.

PMID- 17504340
TI  - The role of primary tumour resection in patients with stage IV colorectal cancer.
AB  - OBJECTIVE: The management of stage IV colorectal cancer is controversial.
      Resection of the primary tumour to prevent obstruction, bleeding or perforation
      is the traditional approach, although survival benefit is undetermined.
      Management consisting of diverting ostomy, enteric bypass, laser recanalization
      or endoscopic stenting is an alternative to radical resection. The purpose of
      this study was to determine the role of resection of the primary tumour in
      patients with stage IV colorectal cancer, with specific attention paid to
      survival benefit and safety. METHOD: This was a retrospective review of all stage
      IV colon and rectal cancer patients in our tumour registry between 1991 and 2002.
      Data collected included patient demographics, presenting symptoms, detail from
      the hospital course including diagnostic data and operative management,
      complications and survival time (days). Survival analysis was performed to assess
      the effect of primary tumour resection on long-term survival. RESULTS: 109
      patients were studied. Sixty-two (57%) patients (group I) underwent resection of
      the primary tumour, whereas 47 (43%) patients (group II) were managed without
      resection. Median survival times for groups I and II were 375 (IQR: 179-759) and
      138 (IQR: 35-262) days respectively (P < 0.0001). After controlling for age, sex,
      tumour location and level of liver involvement as well as liver function,
      patients who underwent resection still survived longer (HR = 0.34, 95% CI: 0.21
      0.55). CONCLUSION: Palliative resection of the primary tumour plays an essential
      role in the management of stage IV colorectal cancer. Resection can offer
      increased survival and is indicated in certain patients with incurable disease.
      Limited metastatic tumour burden of the liver was associated with better survival
      in such patients.

PMID- 17504341
TI  - Management of diverticular fistulae to the female genital tract.
AB  - OBJECTIVE: Fistulae to the female genital tract are an infrequent but severe
      complication of diverticular disease. The purpose of this study was to evaluate
      treatment and outcome in patients with diverticular colo-genital fistulae.
      METHOD: Sixty women treated for diverticular fistulae (DF) to the female genital
      tract during 1992-2004 were identified. Clinic and operative charts were
      reviewed. Mean age was 70 years and mean follow-up time after surgery was 1 year.
      RESULTS: Most common presenting symptoms were vaginal discharge of faeces or gas
      (95% of patients) and abdominal pain (43%). About 75% of patients had undergone a
      hysterectomy. Forty-six patients underwent at least one radiological contrast
      study and the fistula was demonstrated in 35 (76%) patients. Fifty-seven patients
      had surgery, and findings included colo-vaginal fistulae (n = 47), colo-uterine
      fistulae (n = 2) and multiple fistulae involving vagina and other organs (n = 8).
      A sigmoid resection and primary anastomosis was performed in 51 and a Hartmann
      procedure with colostomy in six patients. Sixteen (28%) patients experienced
      morbidity after surgery, including anastomotic dehiscence (n = 4) and ureteric
      injury (n = 3). There was no mortality. CONCLUSION: Diverticular fistulae to the
      female genital tract usually occur in elderly patients with a prior hysterectomy.
      Radiological contrast studies demonstrate the fistulous tract in most cases.
      Sigmoid resection and primary anastomosis results in a satisfactory outcome in
      the majority of patients.

PMID- 17504342
TI  - Diagnostic value of self-reported symptoms in Danish outpatients referred with
      symptoms consistent with colorectal cancer.
AB  - OBJECTIVE: To assess the association between self-reported symptoms and a
      diagnosis of colorectal cancer (CRC) in symptomatic outpatients without CRC risk
      factors, defined by a Danish expert group. METHOD: A cross-sectional study of
      patients aged 40 years and older referred by general practitioners to two Danish
      surgical outpatient clinics for symptoms consistent with CRC during a 16-month
      period. CRC was diagnosed at endoscopy and through follow up. Before their first
      appointment, participants completed a questionnaire about symptoms. RESULTS: The
      study included 2172 patients. Of these, 122 were diagnosed with CRC (5.6%).
      Median age was 61 years (range: 40-97) and 44.0% were men. All symptoms had high
      (93.4-96.8%) negative predictive values for CRC. The highest positive predictive
      values (PPV) were found for dark rectal bleeding (PPV: 20.6%) and CRC was
      diagnosed in a first-degree relative over the age of 50 years (PPV: 11.2%). At
      multiple logistic regression analysis dark rectal blood was the most important
      predictor of CRC (OR: 7.4). Other predictors were age 60 years or older (OR:
      3.0), change in frequency of bowel movements (OR: 2.5), CRC diagnosed in a first
      degree relative over the age of 50 years (OR: 2.6), male gender (OR: 2.2) and
      mono-symptomatic fresh rectal blood (OR: 1.7). CONCLUSION: No self-reported
      symptoms presented by outpatients without CRC risk factors can be used accurately
      to identify patients with CRC with certainty. For clinical purposes self-reported
      symptoms seems thus not to be a useful accurate tool to distinguish between
      symptomatic outpatients with and without CRC.

PMID- 17504343
TI  - A prospective evaluation of occult disorders in obstructed defecation using the
      'iceberg diagram'.
AB  - OBJECTIVE: Surgical treatment of constipation and obstructed defecation (OD)
      carries frequent recurrences, as OD is an 'iceberg syndrome' characterized by
      'underwater rocks' or occult diseases which may affect the outcome of surgery.
      The aim of this study was to evaluate occult disorders, in order to alert the
      clinician of these and minimize failures. METHOD: One hundred consecutive
      constipated patients with OD symptoms, 81 women, median age 52 years, underwent
      perineal examination, proctoscopy, anorectal manometry and anal/vaginal
      ultrasound (US). Anorectal physiology and imaging tests were also carried out
      when indicated, as well as psychological and urogynaecological consultations.
      Symptoms were graded using a modified 1-20 constipation score. Both evident (e.g.
      rectocele) and occult (e.g. anismus) diseases were prospectively evaluated using
      a novel 'iceberg diagram'. The type of treatment, whether conservative or
      surgical, was also recorded. RESULTS: Fifty-four (54%) patients had both mucosal
      prolapse and rectocele. All patients had at least two occult OD-related diseases,
      66 patients had at least three of them: anxiety-depression, anismus and rectal
      hyposensation were the most frequent (66%, 44% and 33%, respectively). The median
      constipation score was 11 (range 2-20), the median number of 'occult disorders'
      was 5 (range 2-8). Conservative treatment was carried out in most cases. Surgery
      was carried out in 14 (14%) patients. CONCLUSION: The novel 'iceberg diagram'
      allowed the adequate evaluation of OD-related occult diseases and better
      selection of patients for treatment. Most were managed conservatively, and only a
      minority were treated by surgery.

PMID- 17504344
TI  - Rectogesic (glyceryl trinitrate 0.2%) ointment relieves symptoms of haemorrhoids
      associated with high resting anal canal pressures.
AB  - OBJECTIVE: Some haemorrhoids are associated with high resting anal canal
      pressures. The aim of this study was to assess if Rectogesic, a topical glyceryl
      trinitrate 0.2% ointment was effective in relieving symptoms of early grade
      haemorrhoids associated with high resting anal canal pressures. METHOD: This was
      a prospective, two-centre, open label study of 58 patients with persistent
      haemorrhoidal symptoms. Patients with first or second degree haemorrhoids and a
      maximum resting anal canal pressure > 70 mmHg were included. Rectogesic was
      applied three times a day for 14 days. Anorectal manometry was performed 30 min
      after the first application of Rectogesic. A 28-day diary was completed during 14
      days of therapy and for 14 days after cessation of treatment. This recorded the
      incidence of rectal bleeding, and visual analogue scales for anal pain,
      throbbing, pruritus, irritation and difficulty in bowel movement. RESULTS:
      Maximum resting anal canal pressures were reduced after application of Rectogesic
      (115.0 +/- 40.4 mmHg vs 94.7 +/- 34.1 mmHg, P < 0.001). In the study period and
      at 14 days after cessation of Rectogesic, there was significant reduction in
      rectal bleeding (P = 0.0002), and significant improvement of anal pain (P =
      0.0024), throbbing (P = 0.0355), pruritus (P = 0.0043), irritation (P = 0.0000)
      and difficulty in bowel movement (P = 0.001). The main adverse event was headache
      in 43.1% of patients. CONCLUSION: Rectogesic is a safe and feasible treatment for
      patients with early grade haemorrhoids associated with high resting anal canal
      pressures.

PMID- 17504345
TI  - Long-term outcome in 445 patients after diagnosis of diverticular disease.
AB  - OBJECTIVE: To describe the long-term outcome after primary diagnosis of
      diverticular disease (DD) with respect to demographics, lifestyle, severity of
      disease and primary treatment. METHOD: Retrospective cohort study of all 445
      consecutive patients admitted to the department during 1989-1995 with the
      diagnosis DD with prospective follow up. Follow up was performed on all patients
      during May 2002 by searching the Danish Patient Register and National Register.
      Logistic regression analyses were applied for defining risk factors for
      readmission or death. For defined risk factors Kaplan-Meier survival statistics
      was performed. RESULTS: The male/female ratio was 30/70. Median age was 75 years
      (men being younger than women, P < 0.01). About 73% received conservative
      treatment primarily. At follow up 35.3% had suffered clinical recurrence of DD,
      of these 15.9% were subsequently operated. However, 3.6% of the patients died of
      causes related to diverticulitis. Possible high-risk groups for recurrence were
      males and their age above 70 years. CONCLUSION: Age and sex are possible
      predictors for recurrence of DD. Elective surgery seems not to be justified after
      just one attack of DD.

PMID- 17504346
TI  - Staged anterior resection and TEM to preserve rectal function in synchronous
      malignant and benign rectal lesions.
AB  - BACKGROUND: Traditionally patients with a high rectosigmoid carcinoma and a
      synchronous large distal rectal adenoma would be treated by low anterior
      resection with associated loss of rectal function. METHOD: Four patients with a
      carcinoma of the upper rectum or distal sigmoid colon and a synchronous distal
      rectal adenoma were treated by high anterior resection followed by staged
      Transanal Endoscopic Microsurgery (TEM) thus conserving the distal rectum.
      Preoperative and postoperative rectal function was assessed using the St. Mark's
      incontinence score. RESULTS: The proximal carcinomas and distal adenomas were 12
      18 cms and 0.5-9 cms respectively from the dentate line. The mean surface area of
      the distal adenomas was 9.7 cms2. There were no deaths or major complications.
      There were no recurrences after a mean follow-up of 31.5 months. Rectal function
      was unchanged in three patients with a minor increase in the score in one.
      CONCLUSION: Staged high anterior resection and 'rEM offers effective treatment of
      synchronous rectosigmoid carcinoma and distal rectal adenoma with preservation of
      rectal function.

PMID- 17504348
TI  - Stable and also unstable coronary disease--COURAGE and the importance of optimal
      medical therapy.

PMID- 17504349
TI  - Confusion still reigns in premature ejaculation management.

PMID- 17504350
TI  - EXACT: rivastigmine improves the high prevalence of attention deficits and mood
      and behaviour symptoms in Alzheimer's disease.
AB  - The objective of this study was to investigate the impact of rivastigmine therapy
      on attention, apathy, anxiety and agitation in patients with mild-to-moderate
      Alzheimer's disease (AD) in a real-world clinical setting. Patients with mild-to
      moderate AD were enrolled in the study by physicians across Canada. They were
      treated with open-label rivastigmine (dose at the discretion of the prescribing
      physicians) for a period of 6 months. Changes from baseline in attention, apathy,
      anxiety and agitation were assessed using an abbreviated Clinician's Global
      Impression of Change at 3- and 6-month visits. The Mini Mental State Examination
      (MMSE) was also used at these visits. Use and changes in use of psychotropic
      medications were recorded, as were changes in caregiver burden. Analyses of
      subgroups (outpatients vs. institutionalised patients) were also performed. A
      total of 2119 patients were enrolled in the study by 375 physicians. At baseline,
      91% had deficits in attention, 85.4% had symptoms of anxiety, 78.5% exhibited
      apathy and 70.1% showed agitation. At 6 months, 67.5% of evaluable patients had
      improved on the symptom of attention, while 62.3%, 62.6% and 56.0% had
      improvements in anxiety, apathy and agitation respectively. The percentages with
      improvements were higher in the institutional subgroup than among outpatients.
      There was an overall mean improvement of 1.1 points on the MMSE at 6 months.
      Approximately four times as many caregivers reported a reduced burden than an
      increased burden at 6 months (40.3% vs. 10.3%). The majority of patients treated
      with rivastigmine experienced improvements in attention, anxiety, apathy and
      agitation. These real-life findings further demonstrate the proven efficacy of
      rivastigmine in patients with mild-to-moderate AD.

PMID- 17504351
TI  - Use of atypical antipsychotic medications in adolescent psychiatric inpatients: a
      comparison with inpatients who did not receive antipsychotic medications during
      their stay.
AB  - The use of atypical antipsychotic medications has been reported to be increased
      in adolescent psychiatric outpatients and to include many patients with non
      psychotic disorders. This study examined the correlates of antipsychotic usage in
      adolescent inpatients and compared their characteristics with a sample of
      adolescent inpatients who did not receive antipsychotics during their
      hospitalisation. A total of 159 consenting consecutive patients treated with
      atypical antipsychotic medications were compared with 150 patients who were
      admitted during the same time period and not treated with antipsychotics. The
      samples were compared for demographic factors, clinical diagnoses, clinical
      symptoms at admission and other medications received during their inpatient stay.
      Sex and ethnicity did not differ significantly as a function of antipsychotic
      mediation status. Significantly few patients with an admission diagnosis of major
      depression received antipsychotic medications and more patients with admission
      diagnosis of bipolar and/or conduct disorder were treated with antipsychotic
      medications. Clinical symptom differences and additional medications received
      were consistent with the differences in admission diagnoses. Despite the fact
      that significantly fewer patients with major depression received antipsychotic
      medications, 47% of the patients who did receive antipsychotic medications in
      this study had an admission diagnosis of major depression. There are several
      differences between these inpatient data and previous studies of outpatient
      claims databases, the majority of adolescent inpatient cases treated with
      antipsychotic medications had admission diagnoses consistent with both adult
      indications and previous research with adolescent patients. These data suggest an
      urgent need to study the safety and efficacy of atypical antipsychotic
      medications on aspects of depression in adolescents.

PMID- 17504352
TI  - Identification and diagnosis of premature ejaculation.
AB  - In sexual health surveys, premature ejaculation (PE) is frequently the most
      common condition reported by men. Men with symptoms of PE often report a
      significant impact of the condition on their lives, experiencing personal
      distress and interpersonal difficulty related to their condition. Unfortunately,
      PE is highly ignored by the patients and the healthcare community. Most of the
      men do not seek medical treatment for their PE. Survey data indicate that men are
      reluctant to discuss sexual issues with physicians and that the physicians
      generally do not initiate discussions of such issues. The aim of this article was
      to discuss the prevalence of this condition and the impact that it has on the
      patient as well as on the partner. We will address the characteristics of PE,
      discuss interview techniques to identify the condition, and outline ways to
      differentiate PE from erectile dysfunction. It is our conclusion that the
      recognition and diagnosis of sexual dysfunctions may subsequently lead to
      treatment opportunities, which, in turn, may improve the quality of life for
      patients with such disorders.

PMID- 17504353
TI  - Control of diabetes and cardiovascular risk factors in patients with type 2
      diabetes in primary care. The gap between guidelines and reality in Spain.
AB  - To evaluate the level and factors affecting control of diabetes and
      cardiovascular risk factors in type 2 diabetes (TYPE 2 DM) patients. Multicentre
      cross-sectional study: a sample of 430 primary care practices across Spain
      selected 1907 type 2 diabetic patients. The first five consecutive ambulatory
      patients with TYPE 2 DM were eligible for the inclusion into the survey. Patients
      were free of known cardiovascular disease (CVD). Control criteria were defined
      based on 2002 American Diabetes Association (ADA) clinical practice
      recommendations. A total of 1907 patients (51% women) aged 63 +/- 9 years.
      Smoking prevalence was 22.6%, 50.6% had levels of A1c < 7%. Mean blood pressure
      (BP) was 148 +/- 17/86 +/- 10 mmHg. Only 7.8% have achieved the target of BP <
      130/80 mmHg. Among the 1180 patients (65%) treated for hypertension, this target
      was attained in only 4.4% of patients. A measurement for low-density lipoprotein
      (LDL) cholesterol was available in 1669 patients (88%). Only 5.9% of patients
      achieved the target of LDL < 100 mg/dl. Among the 638 patients (41.6%) on drug
      treatment for dyslipidaemia, this target was attained in only 5.6% of patients.
      Among type 2 diabetic patients in Spain the prevalence of cardiovascular risk
      factors is high. Control of glycaemia, smoking, BP and LDL are far from optimal
      despite the widespread use of guidelines for the management of diabetes and CVD.
      The application of published recommendations needs to be reinforced.

PMID- 17504354
TI  - Is there a relationship between the blood cholinesterase and QTc interval in the
      patients with acute organophosphate poisoning?
AB  - Organophosphates cause poisoning as a result of the excessive accumulation of
      acetylcholine at the cholinergic synapses due to inhibition of
      acetylcholinesterase (ChE). In the literature, it has been reported that there
      have been electrocardiographic abnormalities, including QT-interval prolongation
      in most patients with acute organophosphate poisoning (OPP), and a relation
      between blood ChE level and clinical severity in acute OPP. The aim of this study
      is to assess the relationship between blood ChE level and QTc interval in the
      patients with acute OPP. This retrospective study consists of 20 patients
      admitted to the emergency intensive care unit. A total of 93 QTc interval and
      blood ChE measures obtained on the same day from 20 cases were compared for their
      correlation. There were prolonged QTc intervals in 35.4% of the ECGs. There was a
      negative correlation between QTc interval and blood ChE measures. In following up
      the patients with acute OPP, QTc interval may be useful when blood ChE levels are
      low and may provide complementary information concerning the severity of
      poisoning. However, further prospective studies, supporting the present results,
      are needed.

PMID- 17504355
TI  - Shift in the burden of cancer towards older people--a retrospective population
      based study.
AB  - Cancer is age-related. However, oncology and palliative medicine services focus
      on the needs of younger and middle-aged adults. This study examined trends in
      cancer deaths across age in Wales over the last 20 years. All Wales death
      certificates from 1981 to 2001 were examined for total and cancer deaths. Place
      of death and age were noted. Total deaths decreased from 35 015 in 1981 to 32 966
      in 2001 while cancer deaths increased from 7369 (21.1% of all deaths) to 8292
      (25.2%). Deaths due to cancer increased in the over 85 years from 9.1% to 13.1%,
      75-84 years (17.1-25.2%), 65-74 years (25-35.7%), 45-64 years (33.5-40.4%) and
      fell from 18.3% to 16.1% in those under 44 years. Cancer deaths over 75 years
      increased from 33.6% of cancer deaths in 1981 to 50.1% in 2001. Cancer deaths in
      the community decreased from 2713 in 1981 to 2153 in 2001 and increased in
      hospital from 4398 to 5185 and care homes from 258 to 954. The increase in
      hospital cancer deaths is mainly because of 75-84 year olds (1207-1840), and the
      over 85 years (294-740). Half of all cancer deaths are now in those over 75
      years. Cancer deaths have shifted from the community to hospital and care homes
      mainly because of cancer in older people. Services need to be developed to target
      this population.

PMID- 17504356
TI  - The impact of the Occupation of Guernsey 1940-1945 on breast cancer risk factors
      and incidence.
AB  - To examine the impact of the German Occupation of Guernsey (1940-1945) on breast
      cancer risk factors and incidence. Under study were 1019 women who stayed, or
      whose mothers had stayed, in Guernsey, and 1358 women evacuated or born to
      evacuated mothers. Amongst those born 1926-1934 who remained in Guernsey, the
      secular trend of earlier menarche disappeared: menarche was delayed by 12 months
      for those born in 1930. By March 2006, 97 breast cancers had been diagnosed, 37
      in the occupied group. Unusually, higher age at menarche appeared to be
      associated with increased risk of breast cancer (>or=14 years vs. <or=13 years:
      HR = 1.52, 95% CI = 0.80-2.92). Separate analyses by birth cohort revealed a non
      significantly higher incidence in the subgroup born from 1926 to 1934 (HR = 1.30,
      95% CI = 0.62-2.76). Delay in menarche among women remaining in Guernsey during
      the Occupation, rather than being protective, was associated with an increased
      risk of breast cancer.

PMID- 17504357
TI  - Randomised, placebo-controlled, double-blind study to investigate the efficacy
      and safety of the acute use of sodium picosulphate in patients with chronic
      constipation.
AB  - There are few studies supporting the effective and safe use of laxatives for
      constipation. This study examined the short-term efficacy and safety of sodium
      picosulphate in patients with chronic constipation. Patients with a history of
      chronic constipation for at least 3 months were randomised to receive 7 mg sodium
      picosulphate or placebo for three consecutive nights. Patients recorded stool
      frequency and consistency, straining, bloating, and pain at baseline and during
      treatment. Vital signs, haematocrit, serum creatinine and electrolytes were
      monitored. Primary end-point for efficacy was the occurrence of a response to
      treatment, defined as improvement in stool frequency and occurrence of straining.
      All 57 randomised patients (sodium picosulphate n = 29, placebo n = 28; mean age
      54.8 and 54.1 years) completed the study. Sodium picosulphate produced a
      treatment response (improved stool frequency and straining) in 82.8% compared
      with 50% in the placebo group (p = 0.010) and reduced bloating more often than
      placebo. There were no serious adverse events and one patient with diarrhoea and
      another with abdominal pain in each treatment group. There were no cardiovascular
      effects, changes in serum haematocrit, creatinine or electrolytes in either
      group. This study confirmed that sodium picosulphate is an effective, well
      tolerated and safe laxative in the acute treatment of constipation.

PMID- 17504358
TI  - Role of imaging end points in atherosclerosis trials: focus on intravascular
      ultrasound.
AB  - Increasing attention has been focused on the appropriate role of surrogate
      markers in the development of novel anti-atherosclerotic therapies. Technological
      advances in imaging modalities allow for visualisation of the entire arterial
      wall. Intravascular ultrasound (IVUS) has been increasingly employed to precisely
      quantify the extent of coronary atherosclerosis. Use of IVUS has provided a
      number of important insights into the natural history of atherosclerosis and the
      remodelling changes of the arterial wall in response to plaque accumulation. More
      recently, clinical trials have employed serial evaluations of arterial segments
      by IVUS to assess the impact of medical therapies.

PMID- 17504359
TI  - Is treatment of early postmenopausal women with bisphosphonates justified?
AB  - The decision to treat women in the early postmenopausal period has come under
      scrutiny because of the low occurrence of fractures in this population and the
      possible lack of cost-effectiveness for individual patients. This article focuses
      on the potential use of bisphosphonates for the prevention and treatment of
      osteoporosis in the early postmenopausal period. Studies have determined that
      there is a relationship between bisphosphonate treatment and bone mineral density
      (BMD) gains, even in women in the early postmenopausal period without a diagnosis
      of osteoporosis. These patients receive benefit from treatment, including
      improvements in BMD levels and fracture protection. Using BMD scores, rates of
      bone turnover, and risk-based diagnostic criteria as part of the decision to
      initiate therapy may allow for the identification of an early postmenopausal
      patient population that would benefit from preventative therapy. This would
      improve the cost-effectiveness of using bisphosphonates for the prevention of
      osteoporosis in this population. The evaluation of women at risk for developing
      osteoporosis should include an assessment of both BMD scores and additional risk
      factors. Early postmenopausal women who are in a high-risk group should be
      considered candidates to receive bisphosphonate therapy.

PMID- 17504360
TI  - Why do patients fail HIV therapy?
AB  - Despite huge advances in terms of the impact of antiretroviral therapy on HIV
      related morbidity and mortality patients continue to fail therapy. We discuss the
      reasons why failure occurs including primary or transmitted resistance, poor
      adherence, toxicity and drug potency. We performed a review of PubMed, Medline
      and recent conference abstracts for information on antiretroviral toxicity,
      adherence, failure and transmitted resistance. Most first-line regimens are now
      similar in potency and, assuming susceptibility to the selected regimen
      determined by genotypic resistance testing, tolerability and toxicity are the key
      issues differentiating currently available agents. New developments such as
      pharmacogenomics have already proven useful in predicting toxicity and may play
      an increasingly important role. With all regimens good adherence remains the key
      to successful therapy; minimising toxicity and other barriers to adherence
      wherever possible is crucial.

PMID- 17504361
TI  - Renal complications in HIV.
AB  - Highly Active Antiretroviral Therapy has revolutionised the care of individuals
      living with HIV-1. As the prognosis for this population has improved, there is an
      increased risk of other major causes of morbidity and mortality, including renal
      disease. This review discusses the frequency and causes of renal pathology, how
      to make the diagnosis and monitor for renal disease in HIV-infected individuals.
      The review was conducted having examined the key evidence focussing upon HIV and
      renal complications obtained from peer-reviewed journals (level of evidence I
      IV). As the population of individuals living with HIV increases, so too does the
      prevalence of renal disease. Physicians should be vigilant and recognise
      individuals at risk of renal complications, and be aware of how to monitor,
      investigate and treat those affected.

PMID- 17504362
TI  - Long-term complications of antiretroviral therapy: lipoatrophy.
AB  - The effective use of potent antiretroviral therapy has dramatically improved the
      life expectancy for HIV-infected individuals. Long-term complications of both HIV
      infection and antiretroviral agents are therefore of increasing concern.
      Lipoatrophy (LA) or fat wasting is a complication most frequently associated with
      nucleoside reverse transcriptase inhibitors, thymidine analogues particularly. LA
      can be stigmatising and is associated with psychosocial complication. It can
      occur in isolation or as part of the 'metabolic' or 'lipodystrophy' syndrome, a
      triad of LA, fat accumulation and metabolic disturbance (insulin resistance and
      dyslipidaemia) with a subsequently increased risk of cardiovascular events. We
      aimed to review the definition, prevalence, pathogenesis, implications and
      treatment of HIV/highly active antiretroviral therapy-associated fat loss. We
      performed a review of PubMed, Medline and recent conference abstracts for
      information on LA. The current treatments available for treating LA are limited.
      Switching away from thymidine analogues can provide a small benefit but
      improvement is, at best, slow and partial. Specific medical therapies such as
      glitazones, metformin and stating have been disappointing to date. Surgical
      fillers can yield marked results but are costly, time consuming and only of value
      for facial LA, not other sites. Ultimately, prevention of this condition is the
      best approach by avoiding thymidine analogues wherever possible or careful
      monitoring with early switching away from these agents. New therapies to treat
      pre-existing fat loss are required.

PMID- 17504363
TI  - Referred otalgia: a structured approach to diagnosis and treatment.
AB  - Many patients who present with otalgia have a normal otological examination, and
      a distant source of pain must be considered. The ear receives an extensive
      sensory innervation arising from six nerve roots. Many other structures in the
      head, neck and thorax share a common neuronal pathway with the ear, and these
      tissues represent the possible sites of disease in the cases of referred otalgia.
      Consequently, the differential diagnosis is extensive and varied. Making an
      accurate diagnosis relies on an understanding of the complex distribution of
      nerve fibres and a structured approach to patient assessment. This article aims
      to classify the aetiology of referred otalgia and to outline current treatments
      for these conditions. The origins of referred otalgia may be as remote as the
      cranial cavity and thorax; however, dental disease, tonsillitis,
      temporomandibular joint disorders and cervical spine pathology represent the most
      frequent causes. Ear pain may also be the first sign of a head and neck
      malignancy. Patients complaining of otalgia, with risk factors for an
      aerodigestive neoplasm, and a normal ENT examination require an urgent
      otolaryngological opinion.

PMID- 17504364
TI  - The Diskus: a review of its position among dry powder inhaler devices.
AB  - The use of dry powder inhalers (DPIs) to administer treatments for respiratory
      diseases has increased significantly in recent years. There is now a wide range
      of DPIs available that vary considerably in design, required operational
      techniques, output characteristics and drug delivery across a range of inhalation
      patterns. Different patient populations may find individual types of DPI easier
      to use correctly than others and selecting the right DPI for particular patient
      requirements will improve compliance with therapy. For example, some DPIs offer a
      greater resistance against inspirational flow rate than others which affects the
      total emitted dose and also fine particle mass of the aerosol released. An
      individual patient may therefore receive different amounts of drug when inhaling
      from different DPIs. Therefore, it is important that the prescriber is fully
      aware of the characteristics of the different types of DPI, so that he or she can
      prescribe the device that is most appropriate to an individual patient's needs.
      This review explores the characteristics of currently available DPIs and
      evaluates their efficacy and patient acceptability. The differences in output
      characteristics, ease of use and patient preferences between available devices is
      shown to affect treatment efficacy and patient compliance with therapy. Changing
      the DPI prescribed to a patient to a cheaper or generic device may therefore
      adversely affect disease control and thereby increase the cost of treatment.

PMID- 17504365
TI  - An unusual presentation of a malignant dysgerminoma.

PMID- 17504366
TI  - Adjunctive zonisamide for treatment refractory anxiety.
AB  - The aim of the study was to assess the use of a novel anticonvulsant, zonisamide,
      in patients with treatment refractory anxiety. Pilot and open study of a cohort
      of patients with anxiety (n = 10), who were deemed partial or non-responders to
      anxiolytic therapy, and received adjunctive zonisamide in a naturalistic fashion.
      The primary outcome measures were the Hamilton Anxiety Scale (HAM-A), the
      Clinical Global Impression of Severity (CGI-S) and the Clinical Global Impression
      of Improvement (CGI-I). Patients included were markedly ill with a mean number of
      previous medication trials of 4.9 +/- 1.9, a baseline HAM-A score of 27.9 +/-
      3.8, and a baseline CGI-S score of 5.7 +/- 0.5. Patients improved significantly
      with an end-point HAM-A score of 12.6 +/- 7.4 (p < 0.001), CGI-S score of 3.6 +/-
      1.3 (p < 0.002) and CGI-I score of 2.5 +/- 1.3. Zonisamide at a mean +/- SD dose
      of 160 +/- 70 mg/day for 9.2 +/- 4.5 weeks was generally well tolerated. Adverse
      events were generally mild, and no patients discontinued zonisamide because of
      side effects. Six patients (60%) met responder criteria at end-point (CGI-I <or=
      2). Results from this pilot and open naturalistic study suggest that zonisamide
      may effectively augment response to anxiolytic medications in patients with
      treatment refractory anxiety. Larger and controlled studies are warranted to
      confirm these preliminary findings.

PMID- 17504367
TI  - The challenge of poor glycaemic control among people with diabetes.

PMID- 17504368
TI  - Diabetes mellitus and cardiovascular risk factors: more insights revisited.

PMID- 17504369
TI  - An outbreak of Streptococcus suis in Chengdu, China.

PMID- 17504370
TI  - Bone turnover 18 months after a single intravenous dose of zoledronic acid.
AB  - Zoledronic acid inhibits bone resorption for up to 12 months. It is not known
      whether the duration of this antiresorptive effect extends beyond this period of
      time. The aim of this study was to evaluate the changes in bone turnover at 12
      months (T12) and 18 months (T18) after a single injection of 4 mg of zoledronic
      acid. It is a prospective, longitudinal study, with a follow-up for 18 months. We
      studied male and female patients (60.5 +/- 11.0 years old), with low bone mineral
      density (BMD) coming from the outpatient clinic in a metabolic bone unit of a
      tertiary care hospital. All patients received a single intravenous dose of 4 mg
      of zoledronic acid, bone turnover markers [serum carboxyterminal telopeptide of
      type I collagen (CTX-I), bone-specific alkaline phosphatase (BSAP)] and BMD
      [lumbar spine (LS) and total hip (TH)] were measured at baseline, and after 12
      months (T12) and 18 months (T18). Median serum CTX-I and BSAP levels were
      suppressed at T12 in comparison with baseline values: 0.183 to 0.039 ng/ml for
      CTX-I (p = 0.0002) and 16.95 to 13.96 U/l for BSAP (p = 0.005). At T18, both CTX
      I and BSAP continued to be suppressed below baseline at 0.108 ng/ml and 12.23 U/l
      (p = 0.009 and p = 0.02, vs. T0). Significant increases in BMD at T18 as compared
      with T12 were observed in patients (median increase 6.1% for LS and 2.0% for TH).
      Zoledronic acid inhibits bone turnover effectively for 12 months, with evidence
      for continued suppression and gains in BMD even after 18 months.

PMID- 17504371
TI  - Clinical trials in gynecological cancer.
AB  - The Gynecologic Cancer Intergroup is comprised representatives from international
      gynecological cancer trials organizations, which collaborate in multicenter
      studies to answer the clinical challenges in gynecological cancer. This review
      article highlights the key clinical questions facing clinical trialists over the
      next decade, the information and infrastructure resources available for trials,
      and the methods of trial development. We cover human papillomavirus (HPV)
      associated neoplasia, including cervical cancer, together with endometrial
      cancer, ovarian cancer, and vulvar cancer. Infrastructure for clinical trials
      includes a database for trials, templates for protocol development, patient
      educational material, and financial support for clinical trials. Other critical
      issues include support from government and charities and government regulations.

PMID- 17504372
TI  - Professionals' and patients' views of routine follow-up: a questionnaire survey.
AB  - Traditionally, women who have been treated for a gynecological cancer have
      undergone long-term follow-up by hospital doctors. Recently, there has been
      interest in alternative models of follow-up, including nurse-based review. The
      project compares patients' and professionals' views of follow-up. A questionnaire
      was completed by 96 women attending routine follow-up clinics and by 32
      professionals involved in delivering follow-up. A large majority of women (82/96,
      92%) and professionals (25/34, 73%) thought that follow-up should be provided by
      a hospital doctor. However, professionals were more likely to think that
      specialist nurses and general practitioners should be involved in the provision
      of follow-up (P < 0.01). Professionals thought that the most important part of
      the follow-up visit was the consultation, whereas women thought it was the
      examination (P < 0.001). Women thought that detection of recurrence was the most
      important reason for continuing surveillance, whereas professionals regarded
      addressing patients' concerns as the primary reason for follow-up (P < 0.001). We
      conclude that the views of women undergoing follow-up after gynecological cancer
      differ significantly from the professionals providing follow-up care. These views
      must be considered when developing alternative follow-up strategies.

PMID- 17504373
TI  - A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line
      treatment of ovarian cancer.
AB  - Ovarian cancer is the fourth leading cause of cancer death among women in the
      United States. First-line chemotherapy offered to patients with ovarian cancer
      generally consists of an intravenous (IV) platinum plus taxane regimen and has
      remained virtually unchanged for the past 10 years. A number of recently
      completed phase III randomized trials in the United States have reported improved
      progression-free survival (PFS) and/or overall survival (OS) with the
      intraperitoneal (IP) administration of cisplatin. The purpose of this study was
      to pool the published data to perform a meta-analysis of randomized trials of IP
      cisplatin in the initial chemotherapy treatment of ovarian cancer patients. This
      study was initiated to obtain a more valid estimate of the therapeutic impact of
      IP treatment for these patients. A search strategy was initiated that searched
      published findings of randomized trials of IP cisplatin therapy from multiple
      sources from January 1990 through January 2006. Six randomized trials of 1716
      ovarian cancer patients were identified and included in this analysis. The pooled
      hazard ratio (HR) for PFS of IP cisplatin as compared to IV treatment regimens is
      0.792 (95% CI: 0.688-0.912, P= 0.001), and the pooled HR for OS is 0.799 (95% CI:
      0.702-0.910, P= 0.0007). These findings strongly support the incorporation of an
      IP cisplatin regimen to improve survival in the front-line treatment of stage
      III, optimally debulked ovarian cancer.

PMID- 17504375
TI  - Cell proliferation activity unrelated to COX-2 expression in ovarian tumors.
AB  - The objective of this study was to assess the expression of Cyclooxygenase-2 (COX
      2) and cell proliferation activity (Ki67 expression) in benign, borderline, and
      malignant serous and mucinous ovarian tumors. Expression of COX-2 and Ki67
      proteins were evaluated by immunohistochemistry, in paraffin-embedded sections of
      ovarian epithelial tumors. The study included 113 serous (67 benign, 15
      borderline, and 31 malignant) and 85 mucinous (48 benign, 28 borderline, and 9
      malignant) tumors, removed from women who underwent laparotomy between January
      1997 and December 2003. From benign to malignant tumors, there was a progressive
      positive trend in COX-2 expression in both serous and mucinous tumors, more
      evident in mucinous ones (P < 0.001). Comparing histologic types, COX-2
      expression was more prominent in serous than in mucinous benign tumors (P <
      0.01), but this difference was not significant in the borderline (P= 0.11) or
      malignant categories (P= 0.71). There was a progressive Ki67 positivity in line
      with the tumor histologic gradient for both serous (P < 0.01) and mucinous
      lesions (P < 0.01), but this increasing expression did not correlate with COX-2
      expression in the present series (P= 0.78). There was a higher COX-2 expression
      in serous ovarian adenomas than in mucinous ones. COX-2 positivity increases in
      line with the morphologic gradient, from benign to malignant in both histologic
      types, but it was more prominent in mucinous lesions, pointing to different
      oncogenic pathways related to different histologic types. A correlation between
      the expression of COX-2 and Ki67 was not found, suggesting that COX-2 may be
      required for carcinogenesis, but this pathway is not responsible for cell
      proliferation in ovarian tumors.

PMID- 17504374
TI  - Differences of chemoresistance assay between invasive micropapillary/low-grade
      serous ovarian carcinoma and high-grade serous ovarian carcinoma.
AB  - The objective of this study was to evaluate the pattern of chemoresistance in
      invasive micropapillary/low-grade serous ovarian carcinoma (invasive MPSC/LGSC)
      and high-grade serous ovarian carcinoma (HGSC) according to extreme drug
      resistance (EDR) assay testing. Surgical specimens of 44 recurrent ovarian cancer
      patients harvested at the time of cytoreductive surgery between August 1999 and
      February 2004 were identified retrospectively from the tumor registry database.
      Thirteen patients (29.5%) had recurrent invasive MPSC/LGSC and 31 (70.5%)
      patients had recurrent HGSC. Eight drugs were evaluated; EDR assay results were
      compared between LGSC and HGSC groups using Fisher exact tests and exact logistic
      regression models. Compared to HGSC, invasive MPSC/LGSC were more likely to
      manifest EDR to the drugs paclitaxel (69% vs 14%, P < 0.001), carboplatin (50% vs
      17%, P= 0.05), cyclophosphamide (40% vs 23%, P= 0.41), gemcitabine (36% vs 19%,
      P= 0.40), and cisplatin (33% vs 28%, P= 0.72) and less likely to be resistant to
      etoposide (0% vs 44%, P= 0.007), doxorubicin (8% vs 45%, P= 0.03), and topotecan
      (8% vs 21%, P= 0.65). Exact logistic regression estimates revealed that invasive
      MPSC/LGSC patients had significantly increased probabilities of paclitaxel
      resistance odds ratio (OR) = 12.5 (95% CI: 2.3-100.0), P= 0.001 and carboplatin
      resistance OR = 4.8 (95% CI: 0.9-25.0), P= 0.07, while the HGSC cases were more
      likely to be resistant to etoposide OR = 12.1 (95% CI: 1.7-infinity), P=0.009 and
      doxorubicin OR = 8.6 (95% CI: 1.0-413.7), P= 0.05. In this retrospective
      analysis, patients with recurrent invasive MPSC/LGSC were more likely to manifest
      EDR to standard chemotherapy agents (platinum and paclitaxel). These observations
      may help to guide chemotherapeutic decision making in these patients if confirmed
      in a large-scale study.

PMID- 17504376
TI  - Human papillomavirus detection in self-collected vaginal specimens and matched
      clinician-collected cervical specimens.
AB  - Human papillomavirus (HPV) detection is an integral part of cervical cancer
      screening, and a range of specimen collection procedures are being tested.
      Preliminary studies have found that the majority of women prefer self-collection
      of vaginal specimens instead of clinician-collected specimens of the cervix. The
      purposes of the current study were to explore the social and behavioral
      predictors of acceptance of self-collection of vaginal specimens among patients
      and to assess concordance in detection of HPV between clinician-collected
      cervical specimens and self-collected vaginal specimens. The study was conducted
      at a university family medicine clinic using a cross-sectional study design, and
      enrollment of women presenting for routine gynecological examination
      consecutively in a period of 1 year, self-administered questionnaires, collection
      of paired vaginal and cervical specimens for HPV DNA using Hybrid Capture 2, and
      cytologic analysis. Most women (79.8% [398/499]) agreed to collect vaginal
      specimens. In our study, 76.6% (216/282) African American women (AA), 88.1%
      (156/176) white non-Hispanic (WNH) women, and 63.4% (26/41) women of other races
      (P < 0.0001) agreed to self-collect vaginal specimens. HPV was detected in 16.0%
      (80/499) of clinician-collected cervical specimens and 26.1% (104/398) of self
      collected vaginal specimens (P < 0.001). HPV detection was concordant in 13.4%
      (53/398) women in both cervical and vaginal specimens. Self-collection of vaginal
      specimens for HPV DNA detection is acceptable to most women presenting for
      routine gynecological examination. WNH women were more likely to obtain self
      collected specimens than AA women. Vaginal specimens were more likely to be
      positive for HPV than were cervical specimens.

PMID- 17504377
TI  - Magnetic resonance imaging appearances of recurrent cervical carcinoma.
AB  - Our aim was to describe the patterns of disease recurrence and residual disease
      in patients treated for cervical carcinoma and to evaluate imaging features,
      which can help to differentiate recurrence and/or residual disease from
      posttreatment change. In a retrospective observational study, magnetic resonance
      imaging (MRI) scans of 48 patients with recurrent or residual cervical carcinoma
      were reviewed by two radiologists. Sixteen patients had undergone primary
      surgical treatment and 32 were treated by chemoradiotherapy. Recurrence was
      confirmed by histology (28), clinical and radiologic progression (6), and by
      patient death (14) due to progressive disease. Magnetic resonance images were
      analyzed for the site of recurrent/residual disease, signal characteristics, and
      invasion of adjacent structures. There were 29 recurrences, while 19 patients had
      residual disease. Most of the recurrences (70.4%) occurred within the first year
      of the start of treatment. Recurrent disease was confined to the central axis of
      the cervix in six patients following chemoradiotherapy and to the vaginal cuff in
      three of these patients following surgery. The recurrent tumor was isointense to
      the adjacent muscles on T1-weighted sequence in 95.3% and hyperintense on T2
      weighted in 88.9%. The cervix was involved in every case of residual disease and
      in 10 of 29 (34.5%) patients with recurrent disease. Recurrent disease was
      present in the vaginal cuff in 14 of 16 (87.5%) postsurgical patients.
      Parametrial invasion was present in 13 (81.3%) patients treated surgically and in
      22 (68.8%) of those receiving chemoradiotherapy. Involvement of the uterosacral
      ligaments was seen in 8 (57.1%) surgical patients and 14 (43.8%) nonsurgical
      ones. Bladder invasion was seen in four (25.0%) patients treated surgically and
      three (9.4%) of those treated with chemoradiotherapy. Radiotherapy change within
      the marrow was seen in 13 (27.0%) patients in total, whereas bone metastases were
      present in 4 (8.3%) patients. Recurrent cervical carcinoma can present with
      varied imaging features. Knowledge of the patterns of recurrence can aid early
      detection and may determine further therapeutic options.

PMID- 17504378
TI  - Human papillomavirus prevalence and predictors for cervical cancer among high
      risk women from Rio de Janeiro, Brazil.
AB  - We assess the prevalence of human papillomavirus (HPV) and cofactors for cervical
      severe disease, as contribution for vaccine strategies at the right moment in
      which Brazilian health authorities have approved an anti-HPV vaccine. A case
      control study was undertaken with 201 women who attended a public health service
      with previous abnormal cytology. The HPV status was ascertained by consensus
      primers My09/11 and typed by 6, 11, 16, 18, 31, 33, 35, and 58 specific primers.
      Patients diagnosed with high-grade squamous intraepithelial lesions (HSIL) and
      cervical cancer were referred as cases (n = 84). Patients with
      normal/inflammatory cervix or carrying benign cervical lesions were included in
      controls (n = 117). The overall prevalence of HPV infection was 75.6%, with 91.7%
      among cases. In spite of HPV 16 being the most frequent type (53.3%), 27.6% of
      infections were attributed to nonvaccine types. High-risk HPV were strongly
      associated to older women (OR = 6.7). Otherwise, age at the first intercourse (OR
      = 7.10), three or more parities (OR = 3.05), abortion episodes (OR = 4.80), and
      smoking (OR = 3.83) conferred a heavy effect in younger women. Among mediators
      affecting the progress from HSIL to cancer, age played the main role in easing
      the progression (OR = 1.09, P = 0.002) followed by education level (OR = 4.20, P
      = 0.066). White ethnia showed to be a protective factor (OR = 0.32, P = 0.055).
      Predictors from HPV exposure to malignant disease include demographic and
      behavioral factors. Public policies such as improvement of education and
      continued prevention campaigns might contribute to reduce this picture. This work
      also gives background, in identifying a target population, for implementing
      future vaccine strategies.

PMID- 17504379
TI  - Primary treatment of Bartholin's gland carcinoma with radiation and
      chemoradiation: a report on ten consecutive cases.
AB  - We reviewed our experience with primary radiation therapy for Bartholin's gland
      carcinoma (BGC) as an alternative to traditional surgical treatment. A
      retrospective study reviewed records from the Cancer Data Registry and Research
      Patient Data Registry from 1986 to 2002. Charts of ten women identified with BGC
      were reviewed for demographic information, presenting symptoms, tumor
      characteristics, treatment modalities, and complications, as well as for
      recurrence and survival. The incidence of BGC was 2.13% of all invasive vulvar
      cancer cases at the Massachusetts General Hospital (MGH). Four patients presented
      with clinical stage I disease, one with stage II, three with stage III, and two
      with stage IV. The median age at diagnosis was 63.5 years. There were five
      squamous cell carcinomas, two adenoid cystic carcinomas, two mucinous
      adenocarcinomas, and one small-cell carcinoma. After a change in treatment policy
      in 1986 from primary surgery that had often required postoperative radiation
      therapy, ten consecutive patients were treated with primary radiotherapy or
      chemoradiation therapy. Treatment included teletherapy combined with a boost to
      the primary site, regional nodes and/or interstitial brachytherapy. Short-term
      complications were mild and well tolerated; one patient developed late radiation
      associated pelvic fractures. Four tumors recurred with a mean time to recurrence
      of 31.2 months. The median follow-up was 87.2 months (45-142). Three- and 5-year
      survivals were 71.5% and 66%, comparable to outcomes after surgery and
      postoperative radiation therapy. We conclude that primary radiation or
      chemoradiation therapy offers an effective alternative to surgery in the
      treatment of BGC with preservation of genital function and low morbidity.

PMID- 17504380
TI  - The nonsynonymous single nucleotide polymorphisms of DNA repair gene XRCC1 and
      susceptibility to the development of cervical carcinoma and high-risk human
      papillomavirus infection.
AB  - To evaluate contribution of single nucleotide polymorphisms (SNPs) of X-ray
      repair cross-complementing group 1 (XRCC1) gene to the risk of cervical
      carcinoma, we conducted a case-control study of 1012 patients including 539
      carcinoma and 473 cervical intraepithelial neoplasia (CIN) and 800 normal women
      controls and genotyped three XRCC1 SNPs (Arg194Trp, Arg280His, and Arg399Gln). We
      found that compared with the Arg399Gln (GG), subjects carrying the homozygous
      Gln399Gln (AA) genotype had a significantly 2.32-fold increased risk of cervical
      carcinoma (95% CI 1.47-3.65), heterozygous Arg399Gln (GA) genotype were also
      associated with a significantly increased risk of cervical carcinoma, with the
      adjusted odds ratio (OR) being 1.58 (95% CI 1.24-2.00). Similarly, compared with
      Arg194Arg (CC) wild-type genotype, elevated risks were associated with the
      Trp194Trp (TT) for carcinoma (ORs and 95% CIs being 2.09 [1.45-3.02]) but not for
      heterozygote Arg194Trp (CT). In addition, three common haplotypes were found to
      be associated with an increased risk of cervical carcinoma. Using 194Arg-280Arg
      399Arg as the reference, the OR and 95% confidence interval for 194Arg-280Arg
      399Gln, 194Arg-280His-399Arg, 194Trp-280Arg-399Arg were 2.30 (1.86-2.85), 1.85
      (1.41-2.41), 1.98 (1.62-2.40), respectively. The significantly increased risk
      associated with the haplotypes was also observed in squamous cell carcinoma (SCC)
      for all three common haplotypes using 194Arg-280Arg-399Arg as the reference.
      Neither difference was found for adenocarcinoma and CIN. All three SNPs and
      haplotypes did not confer more risk of high-risk human papillomavirus infection
      in carcinoma, CIN, and normal subgroup. Our findings suggest that XRCC1
      polymorphisms including genotypes and haplotypes contribute to susceptibility to
      the development of cervical SCC, and the increased susceptibility is probably not
      through increasing susceptibility to human papillomavirus infection.

PMID- 17504381
TI  - CXCR4 expression is associated with pelvic lymph node metastasis in cervical
      adenocarcinoma.
AB  - The aim of this study is to investigate the expression of CXCR4 receptor in
      cervical adenocarcinoma and related mechanisms involved in pelvic lymph node
      metastasis. Immunohistochemistry was used to evaluate the expression of CXCR4 and
      the association of pelvic lymph node metastasis in archived tissue from clinical
      stage IB cervical adenocarcinomas (n = 37) and from benign specimens obtained at
      hysterectomy for other causes (n = 48). The HeLa cell (cervical adenocarcinoma
      derived cell) line that expresses CXCR4 was used to study the interaction between
      the CXCR4 receptor and stromal cell-derived factor 1alpha (SDF-1alpha). Cell
      migration assays, cell numbers, flow cytometry, cell proliferation assay, and
      western blot were used to study the function of CXCR4 and its downstream signal
      transduction. The positive cases were semiquantitatively divided into three score
      classes according to their staining. Tumors with strong CXCR4 stainings were more
      likely to have pelvic lymph node metastasis than those with weak or negative
      stainings (87.5% vs 34.5%; P = 0.014). Only 25% of the benign specimens had weak
      or negative staining for CXCR4. Functioning CXCR4 receptor was expressed on HeLa
      cells. SDF-1alpha provoked significant signal transduction events, including
      chemotaxis and rescue from apoptosis. These actions were apparently mediated by
      the activation and phosphorylation of the extracellular signal-regulated kinase
      1/2 and AKT pathways. We conclude CXCR4 expression is associated with cervical
      adenocarcinoma cell migration and proliferation, and primary cervical
      adenocarcinoma cells expressing CXCR4 are significantly more likely to
      metastasize to pelvic lymph nodes.

PMID- 17504383
TI  - The prognostic value of PTEN, p53, and beta-catenin in endometrial carcinoma: a
      prospective immunocytochemical study.
AB  - Mutations of the PTEN, p53, and beta-catenin genes are the most frequent
      molecular defects in endometrial carcinomas. The aim of this study was to
      investigate their prognostic significance in this form of cancer. Imprint smears
      were obtained from 80 fresh endometrial tumor specimens and studied
      immunocytochemically for the expression of PTEN, p53, and beta-catenin proteins.
      The staining pattern was correlated with several well-established prognostic
      parameters, including 5-year survival. Positive staining of p53 was significantly
      correlated with increased stage (P < 0.0001), lymph node metastases (P = 0.001),
      and a nonendometrioid histology (P = 0.001). On the contrary, positive beta
      catenin expression was significantly associated with decreased stage (P = 0.002),
      decreased grade (P = 0.007), and a negative lymph node status (P = 0.023). PTEN
      positivity was correlated with decreased stage (P = 0.002) and negative lymph
      nodes (P = 0.008). All the three markers affected survival significantly in
      univariate analysis but only beta-catenin had an independent prognostic impact.
      An independent prognostic significance was also shown for PTEN in the stage I
      subgroup of patients. The results of our study indicate that loss of beta-catenin
      expression is a strong and independent predictor of an unfavorable outcome in
      patients with endometrial carcinoma. Loss of PTEN may also be associated with a
      worse prognosis in patients with early-stage disease.

PMID- 17504382
TI  - Gene expression profiles in squamous cell cervical carcinoma using array-based
      comparative genomic hybridization analysis.
AB  - Our aim was to identify novel genomic regions of interest and provide highly
      dynamic range information on correlation between squamous cell cervical carcinoma
      and its related gene expression patterns by a genome-wide array-based comparative
      genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from
      KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection
      assay was performed to obtain DNA samples from paraffin-embedded cervical tissues
      of cancer as well as of the adjacent normal tissues. The bacterial artificial
      chromosome (BAC) array used in this study consisted of 1440 human BACs and the
      space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed
      the differential changes of the cervical cancer-associated genetic alterations.
      The analysis limit of average gains and losses was 53%. A significant positive
      correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2
      changes through the cervical carcinogenesis. The regions of high level of gain
      were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the
      regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and
      11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3,
      HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The
      genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B,
      and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations
      were maintained in cervical cancer that were critical to the malignant phenotype
      and may give a chance to find out possible target genes present in the gained or
      lost clones.

PMID- 17504384
TI  - High-grade broad ligament cancer of mullerian origin: immunohistochemical
      analysis of a case and review of the literature.
AB  - Malignant neoplasms arising in the broad ligament are quite unusual. Although
      tens of broad ligament cancers of low potential malignancy have been documented,
      there have been only two reports of high-grade cases. Furthermore, it remains
      controversial whether broad ligament tumors are mesonephric (wolffian) or
      paramesonephric (mullerian) in origin. This case study reports a 49-year-old
      nulliparous woman who, during her follow-up for breast cancer, demonstrated a 39-
      x 32-mm solid and poorly differentiated adenocarcinoma within the broad ligament
      of the right adnexa. Because of its rarity and poor differentiation,
      immunohistochemical analysis was performed to identify the primary malignancy and
      determine its origin. Positive expression of WT1, CA125, and ER and negative
      expression of GCDFP-15, HER-2, and PgR in broad ligament cancer, in conjunction
      with positive expression of GCDFP-15 and ER and negative expression of WT1, HER-2
      and PgR in the previous breast cancer, suggested broad ligament cancer to be a
      gynecological primary malignancy with serous characteristics rather than a
      metastasis from the previous breast cancer. In addition, EMA-positive and CK7
      negative expression indicated a mullerian origin. Broad ligament cancers of
      mullerian origin occur predominantly in women of reproductive age, most of whom
      are infertile or nulliparous. This feature, together with the positive expression
      of ER in this case, may raise the possible hormonal influence on the etiology of
      broad ligament cancer of mullerian origin.

PMID- 17504385
TI  - Primary cervical choriocarcinoma: report of four cases and literature review.
AB  - Primary cervical choriocarcinoma is very rare. So far, approximately 82
      authenticated cases have been reported in the literature. We present additional
      four cases of primary cervical choriocarcinoma; the clinical features,
      differential diagnosis, and appropriate management are reported. Up to January
      2005, all the four patients survived.

PMID- 17504386
TI  - Occult metastatic lung carcinoma presenting as locally advanced uterine
      carcinosarcoma on positron emission tomography/computed tomography imaging.
AB  - Increasingly, positron emission tomography/computed tomography (PET/CT) is being
      used as a tumor surveillance modality for multiple tumor types. A 73-year-old
      postmenopausal female with stage IV nonsmall cell lung cancer presented after a
      PET/CT demonstrated focal uptake in the superior and lateral aspects of the
      uterus. The patient reported a history of intermittent postmenopausal bleeding
      and an endometrial biopsy documented uterine carcinosarcoma. Postoperative
      pathologic review and immunohistochemical staining with thyroid transcription
      factor-1 revealed metastatic adenocarcinoma consistent with her lung primary in
      her uterus and adnexa. Our case represents a rare occurrence in which lung cancer
      has metastasized to multiple female pelvic organs. Increasing use of PET/CT may
      lead to the discovery of occult metastases masquerading as a second primary
      malignancy.

PMID- 17504387
TI  - Fetal jaw movement affects development of articular disk in the temporomandibular
      joint.
AB  - Previous studies suggest that jaw movement is an important factor in the
      development of cartilage in the temporomandibular joint during the prenatal and
      postnatal periods. In the present study, the effects of fetal jaw movement on the
      articular disk were studied in mice by restraining the opening movement of the
      mouth using the mouse exo utero development system. At embryonic day 18.5, the
      articular disk was reduced in size in the embryos whose maxilla and mandible were
      sutured (sutured group) and there were changes in the cellular morphology of the
      mesenchymal cells in the disk. The volume of the articular disk, the total number
      of cells and the number of 5-bromo-2'-deoxyuridine-positive cells in the
      articular disk were significantly lower in the sutured group than in the non
      sutured control group. Our data revealed that fetal jaw movement affects the
      development of the articular disk in the temporomandibular joint.

PMID- 17504388
TI  - Patterns of chromosomal deletions identified by a birth defects registry, Hawaii,
      1986-2003.
AB  - The aim of the investigation was to describe the chromosomal deletions identified
      by a birth defects registry with respect to the chromosomes involved, pregnancy
      outcome, method of diagnosis, inheritance, sex, and the diagnosis of major
      structural birth defects. Cases were derived from a population-based birth
      defects registry in Hawaii and comprised all infants and fetuses with chromosomal
      deletions delivered during 1986-2003. A total of 71 cases were identified through
      a statewide birth defects registry in Hawaii during 1986-2003. The chromosomes
      involved in the greatest proportion of deletions were chromosomes 22 (14.1%), 4
      (11.3%), and 5 (11.3%). Live births accounted for 58 (81.7%) of the cases.
      Diagnosis was made by amniocentesis or chorionic villus sampling in 19 (26.8%) of
      the cases. Of the 18 cases with known inheritance, the deletion was inherited in
      5 (27.8%) and de novo in 13 (72.2%). Males accounted for 28 (39.4%) and females
      for 43 (60.6%) of the cases. Major structural birth defects were identified in 51
      (71.8%) of the cases. Chromosomal deletions do not appear to affect all
      chromosomes equally. Most of the chromosomal deletions that were detected
      occurred among live births and were de novo conditions. Infants and fetuses with
      chromosomal deletions are more likely to be females and to be associated with
      major structural birth defects.

PMID- 17504389
TI  - Development of the pons in human fetuses.
AB  - Morphometric and histological studies of the pons were performed by light
      microscopy in 28 cases of externally normal human fetuses ranging from 90 to 246
      mm in crown-rump length (CRL) and from 13 to 28 weeks of gestation. The
      brainstems of fetuses were embedded in celloidin or paraffin, and transverse
      sections were prepared. The pons was divided into two regions at the most ventral
      margin of the medial lemniscus at the level of the motor trigeminal nucleus. The
      relationships between the total dorsoventral length, ventral length, and dorsal
      length of the pons versus CRL and gestational ages were calculated, and empiric
      formulas were fitted. It was found that the ventral portion increased in size
      more rapidly than the dorsal portion. The proportion of the ventral portion in
      the total dorsoventral length was constitutively higher than that of the dorsal
      portion in the present range of CRL. In the pontine nuclei, from 235 mm in the
      CRL, some large cells with rich cytoplasm, pale nuclei, and a distinct nucleolus
      appeared on the dorsal side of the pyramidal tract. According to Weigert stained
      preparations, the first myelinated fibers in each motor root of the trigeminal,
      abducent, and facial nerves were recognized at 130-140 mm in CRL and the medial
      lemniscus at 230-235 mm.

PMID- 17504390
TI  - Cerebro-fronto-facial syndrome (Dandy-Walker Variant and frontofacial
      dysmorphisms): report of the first case identified by increased nuchal
      translucency beyond 13(+6) weeks.
AB  - A 32-year-old gravida 2, para 1 woman, with a previous uneventful pregnancy,
      underwent first trimester ultrasound screening for Down syndrome at 13 weeks
      according to the Fetal Medicine Foundation guidelines
      (http://www.fetalmedicine.com/pdf/11-14/english/FMF-English.pdf). The ultrasound
      showed increased nuchal translucency (NT) of 8.9 mm with an estimated risk of
      Down syndrome of 1:8. Fetal karyotype was normal 46,XX by chorionic villus
      sampling. The patient underwent weekly ultrasound and at 19 weeks of gestation, a
      dilatation of the 4th ventricle with partial agenesis of the cerebellar vermis
      and normal posterior fossa were observed by transvaginal transcerebellar section
      of the fetal head. This finding was consistent with a diagnosis of Dandy-Walker
      variant and the patient opted for termination of pregnancy after extensive
      counselling. Autoptic examination confirmed the prenatal ultrasonographic
      findings and revealed signs of an underlying cerebro-fronto-facial syndrome due
      to the presence of facial dysmorphisms consistent with horizontal eyelid, high
      nasal root, low set ears and a wide forehead. Increased NT is not only a common
      phenotypic expression of chromosomal abnormalities, but is also associated with a
      wide range of fetal defects and genetic syndromes. Careful ultrasonographic
      follow-up is mandatory in all cases of increased first trimester nuchal
      translucency with normal karyotype in order to identify associated anomalies.

PMID- 17504391
TI  - Abdominal dystocia in a case of undetected intrauterine meconium peritonitis due
      to cystic fibrosis.
AB  - The case of a 36 year-old primigravida is presented. After a normal anomaly scan
      at 22 weeks and a normal pregnancy, she went into labor at term. Dystocia due to
      massive abdominal distension complicated the second stage. The newborn girl had
      meconium peritonitis with colonic perforation and required colonic resection with
      colostomy. Genetic testing detected cystic fibrosis. In this case complex
      meconium peritonitis developed silently (without any clinical sign) after a
      normal anomaly scan. This has not been reported since the start of the widespread
      use of obstetric ultrasound. Late meconium peritonitis can escape detection and
      should be thought of in cases of unexpected abdominal distension causing
      dystocia.

PMID- 17504392
TI  - Comments from the Developmental Neurotoxicology Committee of the Japanese
      Teratology Society on the OECD Guideline for the Testing of Chemicals, Proposal
      for a New Guideline 426, Developmental Neurotoxicity Study, Draft Document
      (October 2006 version), and on the Draft Document of the Retrospective
      Performance Assessment of the Draft Test Guideline 426 on Developmental
      Neurotoxicity.
AB  - In October 2006, a new revision of the draft guideline (OECD Guideline for the
      Testing of Chemicals, Proposal for a New Guideline 426. Developmental
      Neurotoxicity Study) and Draft Document of the Retrospective Performance
      Assessment (RPA) of the Draft Test Guideline 426 on Developmental Neurotoxicity
      were distributed following incorporation of the results of the Expert
      Consultation Meeting in Tokyo on May 24-26, 2005. The draft guideline consists of
      50 paragraphs and an appendix with 102 references; and the draft RPA consists of
      37 paragraphs with 109 references. National coordinators were requested to
      arrange for national expert reviews of these draft documents in their member
      countries. Members of the Developmental Neurotoxicology (DNT) Committee of the
      Japanese Teratology Society (JTS) reviewed, discussed, and commented on the draft
      Test Guideline Proposal. The DNT Committee of the JTS also commented on the draft
      document of the RPA. These comments were sent to the OECD Secretariat. The DNT
      Committee of the JTS expects the comments to be useful for the finalization of
      these draft documents.

PMID- 17504393
TI  - A history of the Section for Medical Microbiology within the Swedish Society of
      Medicine. 1808-1907.

PMID- 17504394
TI  - From the 1960s until today.

PMID- 17504396
TI  - Clinical virology in Sweden.

PMID- 17504395
TI  - Clinical bacteriology--the recent past.

PMID- 17504397
TI  - Developments in the recent past--immunology.

PMID- 17504398
TI  - Developments in the recent past--hospital hygiene and antimicrobials. Medical
      Microbiology: a tool in control of health-care-associated infections.

PMID- 17504399
TI  - Clinical microbiology informatics--developments in Sweden. 1939.

PMID- 17504400
TI  - On the occurrence of a factor in human serum activating the specific agglutintion
      of sheep blood corpuscles. 1939.

PMID- 17504402
TI  - Experimental studies on the role of plasma cells as antibody producers. 1942.

PMID- 17504404
TI  - Antigen- antibody reactions in gels. 1952.

PMID- 17504406
TI  - Hereditary serological human serum groups.

PMID- 17504408
TI  - The impact on the developing embryo and newborn animal of adult homologous cells.

PMID- 17504410
TI  - A normally occurring Staphylococcus antibody in human serum.

PMID- 17504412
TI  - A new type in the gm system.

PMID- 17504414
TI  - The influence of thymectomy on antibody formation.

PMID- 17504416
TI  - Heparin and related polyionic substances as virus inhibitors. 1964.

PMID- 17504418
TI  - Two further cases, bacteriologically verified of human infection with
      "pasteurella X" (syn. Yersinia enterocolitica). 1966.

PMID- 17504420
TI  - Bile acid transformations by microbial strains belonging to genera found in
      intestinal contents. 1967.

PMID- 17504422
TI  - Heterotransplantation of a human malignant tumour to "nude" mice. 1969.

PMID- 17504424
TI  - Antibiotic sensitivity testing. 1971.

PMID- 17504426
TI  - Pseudomonas aeruginosa infection in cystic fibrosis. 1974.

PMID- 17504428
TI  - Serology Of Neisseria gonorrhoeae classification by Co-agglutination. 1980.

PMID- 17504430
TI  - Clinical studies of acinetobacter classified By DNA-DNA hybridization. 1989.

PMID- 17504432
TI  - New receptor for human plasminogen on gram positive cocci. 1989.

PMID- 17504434
TI  - Classification, identification and subtyping of bacteria based on pyrosequencing
      and signature matching of 16s rDNA fragments. 2002.

PMID- 17504437
TI  - Evidence that down regulation of hypothalamic KiSS-1 expression is involved in
      the negative feedback action of testosterone to regulate luteinising hormone
      secretion in the adult male rhesus monkey (Macaca mulatta).
AB  - In the male monkey, luteinising hormone (LH) secretion is regulated by a negative
      feedback action of testicular testosterone that is exerted indirectly at the
      hypothalamic level to decelerate pulsatile gonadotrophin-releasing hormone
      release (GnRH). The purpose of the present experiment was to investigate whether
      the kisspeptin-G protein-coupled receptor 54 (GPR54) signalling pathway is
      involved in mediating the action of testosterone to suppress GnRH release in the
      monkey, as has been indicated by studies of nonprimates. To this end, 12
      castrated adult male rhesus monkeys were implanted with either testosterone
      containing or empty Silastic capsules. Testosterone treatment produced a square
      wave increment in circulating testosterone levels within the physiologic range.
      After suppression of LH and follicle-stimulating hormone secretion was
      established at 5-6 weeks of testosterone exposure, the animals were killed and
      expression of the genes encoding for kisspeptin, GPR54 and GnRH determined in the
      mediobasal hypothalamus and preoptic area of both treated and control animals
      using RNase protection assays. The suppression in pituitary gonadotrophin
      secretion was associated with a reduction in kisspeptin mRNA levels in the
      mediobasal hypothalamus, but not the preoptic area. GPR54 mRNA levels, on the
      other hand, were not influenced by testosterone treatment. These results are
      consistent with those previously reported for the rodent, and suggest that the
      neurobiology of the negative feedback action of testicular testosterone on LH
      secretion in the monkey, a representative higher primate, may be mediated by
      kisspeptinergic neurones upstream to the GnRH network.

PMID- 17504438
TI  - Presence of oxytocin receptors in the gonadotrophin-releasing hormone (GnRH)
      neurones in female rats: a possible direct action of oxytocin on GnRH neurones.
AB  - Gonadotrophin-releasing hormone (GnRH) neurones constitute the final output
      pathway of a neuronal network that controls the preovulatory luteinising hormone
      (LH) surge and ovulation. Throughout the reproductive cycle, several
      neurotransmitters stimulate and inhibit the activity of GnRH neurones, including
      oxytocin. The central administration of oxytocin antiserum abolishes the pro
      oestrous LH surge whereas oxytocin stimulates GnRH secretion from hypothalamic
      explants suggesting an oxytocin central action. Within the GnRH neuronal
      population in the rat, GnRH cells in the medial preoptic area (MPOA) are
      activated at the time of the LH surge. Thus, we hypothesised that GnRH neurones
      in the MPOA may express oxytocin receptors, and that oxytocin neurones in the
      supraoptic nucleus (SON) and paraventricular nucleus (PVN) may be differentially
      activated during the oestrous cycle. Oxytocin receptors mRNA was detected in the
      MPOA using reverse transcription-polymerase chain reaction. In animals in either
      metoestrus or pro-oestrus, double-label immunofluorescence indicated that
      approximately 10% of GnRH neurones in the MPOA coexpressed oxytocin receptors and
      that a few oxytocin fibres are located in the vicinity of these GnRH neurones.
      However, other neurones positive for the oxytocin receptors were found near GnRH
      neurones. At both oestrous stages, double-label immunofluorescence revealed that
      approximately 30% of oxytocin neurones in the SON were Fos-positive whereas
      oxytocin neurones in the PVN were consistently Fos-negative. Together, these data
      suggest that oxytocin may directly control neuronal activity in a subpopulation
      of GnRH neurones. Moreover, both oxytocin neuronal activity and the oxytocin
      receptor expression on GnRH cells are not influenced by oestrogen.

PMID- 17504439
TI  - Changes in insulin, glucose and ketone bodies, but not leptin or body fat content
      precede restoration of luteinising hormone secretion in ewes.
AB  - The reproductive system, including pulsatile luteinising hormone (LH) secretion,
      is inhibited by deficits in energy availability and restored by energy surfeits.
      Plasma LH, insulin, leptin, ghrelin, glucose, ketone body, and nonesterified
      fatty acid concentrations were measured in ovariectomised, food-restricted ewes
      before and after return to ad libitum feeding to determine the factors that
      change in time to account for the restoration of pulsatile LH secretion. At 07.00
      h, blood was sampled every 10 min for 5 h from ovariectomised, hypogonadotrophic,
      chronically food-restricted and ad libitum-fed ewes (Fed). At 12.00 h, four of
      the food-restricted sheep were given ad libitum access to food (Re-Fed), while
      three ewes continued to be food restricted (Restricted). Sampling continued for 5
      h and resumed again on the mornings of days 2, 4, and 9. A pulse of LH was seen
      within 1 h of re-feeding in all Re-Fed ewes, and interpulse interval (IPI) was
      significantly shorter in Re-Fed compared to Restricted ewes and longer than in
      Fed ewes during the period after re-feeding. Re-Fed LH IPI was not restored to
      that of Fed ewes until sometime between days 4 and 9. The first pulse occurred
      within minutes, whereas restoration of IPI occurred after 4-8 days. Prior to the
      initial LH pulses seen in Re-Fed ewes, plasma ketone bodies first fell and then
      rose to levels significantly above those in Restricted ewes. Significant changes
      in circulating insulin, ghrelin, glucose, and total ketone body concentrations,
      daily food intake and lean body mass preceded restoration of Re-Fed LH IPI some
      time between days 4 and 9, but there were no significant changes in adiposity or
      circulating leptin concentrations, consistent with the hypothesis that LH pulses
      are reinitiated by changes in the availability of oxidisable metabolic fuels and
      possibly insulin, but not leptin concentrations.

PMID- 17504440
TI  - Region- and sex-specific modulation of anxiety behaviours in the rat.
AB  - Recent studies in both animals and humans indicate that gonadal hormones have
      profound control over emotional states, and certainly contribute to the increased
      occurrence of psychiatric illness in women. Reports, as reviewed here, suggest
      that two important regions of the limbic system, the central nucleus of the
      amygdala (CeA) and the bed nucleus of the stria terminalis (BNST), control
      different aspects of emotional behaviour. Short-term cue-specific emotional
      responses, like Pavlovian fear conditioning, require activation of the CeA, while
      long-duration and contextual emotional responses, are dependant on the BNST.
      There is accumulating experimental evidence that gender and sex hormones
      specifically modulate BNST-mediated anxiety behaviours. Moreover, the functional
      separation between the CeA and the BNST may be exaggerated during lactation in
      the rat, a time of profound hormonal and behavioural change. In this study, the
      effects of sex hormones on fear and anxiety are reviewed with an emphasis on the
      differential effects of these hormones on functions subserved by the BNST as
      opposed to the CeA. Studies, as highlighted here, looking at sex hormone and
      gender effects on the ability of corticotrophin-releasing factor and bright
      ambient light to enhance startle, emphasise the importance of understanding both
      the effect of, and brain region where, gonadal hormones exert their control over
      emotional behaviour.

PMID- 17504441
TI  - Terminal nerve gonadotrophin-releasing hormone (GnRH) neurones express multiple
      GnRH receptors in a teleost, the dwarf gourami (Colisa lalia).
AB  - Gonadotophin-releasing hormone (GnRH) peptide released from the terminal nerve
      (TN)-GnRH neurones of the dwarf gourami primarily modifies the electrical
      properties of various neurones, including the TN-GnRH neurones themselves.
      However, our knowledge on the expression of GnRH receptors (GnRHRs) in the TN
      GnRH neurones is still limited. Here, we used the single-cell reverse
      transcriptase-polymerase chain reaction after whole-cell patch-clamp recording to
      study the distribution of various GnRHR types expressed in the individual TN-GnRH
      neurones. We found that TN-GnRH neurones express two of the three types of GnRHRs
      cloned in the dwarf gourami: GnRHR1-2 and -R2, but not -R1-1. Furthermore, in
      agreement with our previous findings, all TN-GnRH neurones contained mRNAs of
      salmon GnRH but not chicken GnRH-II.

PMID- 17504442
TI  - c-Myc partially mediates IFNgamma-induced apoptosis in the primary hepatocyte.
AB  - Interferon-gamma (IFNgamma) is a central component of the complex cytokine and
      inflammatory response that contributes to liver cell injury in hepatitis. We
      report that in the primary hepatocyte IFNgamma synergizes with the
      mechanistically distinct apoptotic stimuli CD95, tumour necrosis factor-alpha
      (TNFalpha) and UV-irradiation. For the first time in primary hepatocytes, we show
      that IFNgamma-mediated apoptotic signalling requires the cell surface interaction
      of CD95 and its ligand, and we demonstrate that IFNgamma induces soluble CD95
      ligand release from hepatocyte monolayers. Utilizing c-myc phosphorothioate
      antisense fragments, we suppresses hepatocyte apoptosis induced by IFNgamma. In
      summary, we identify apoptotic pathways that contribute to IFNgamma-mediated cell
      death. The hepatocellular response to IFNgamma signalling can be modulated by
      cytokines and by the interruption of CD95 interaction with its ligand. We present
      evidence to suggest that c-myc contributes to IFNgamma signalling.

PMID- 17504443
TI  - Effect of reactive oxygen intermediaries on the viability and infectivity of
      Mycobacterium lepraemurium.
AB  - Murine leprosy is a natural disease of the mouse, the most popular model animal
      used in biomedical research; the disease is caused by Mycobacterium lepraemurium
      (MLM), a successful parasite of macrophages. The aim of the study was to test the
      hypothesis that MLM survives within macrophages because it highly resists the
      toxic effects of the reactive oxygen intermediaries produced by these cells in
      response to infection by the microorganism. MLM cells were incubated in the
      presence of horseradish peroxidase (HRPO)-H(2)O(2)-halide for several periods of
      time. The peroxidative effect of this system was investigated by assessing the
      changes occurred in (a) lipid composition; (b) viability; and (c) infectivity of
      the microorganism. Changes in the lipid composition of peroxidated- vs. intact
      MLM were analysed by thin layer chromatography. The effect of the peroxidative
      system on the viability and infectivity of MLM was measured by the alamar blue
      reduction assay and by its ability to produce an infection in the mouse,
      respectively. Peroxidation of MLM produced drastic changes in the lipid envelope
      of the microorganism, killed the bacteria and abolished their ability to produce
      an in vivo infection in the mouse. In vitro, MLM is highly susceptible to the
      noxious effects of the HRPO-H(2)O(2)-halide system. Although the lipid envelope
      of MLM might protect the microorganism from the peroxidative substances produced
      at 'physiological' concentrations in vivo, the success of MLM as a parasite of
      macrophages might rather obey for other reasons. The ability of MLM to enter
      macrophages without triggering these cells' oxidative response and the lack of
      granular MPO in mature macrophages might better explain its success as an
      intracellular parasite of these cells.

PMID- 17504444
TI  - Ischaemia and reperfusion effects on skeletal muscle tissue: morphological and
      histochemical studies.
AB  - This was a study on the oxidative stress due to ischaemia (I) and reperfusion (R)
      in skeletal muscle tissue. Using a tourniquet, groups of rats were submitted to
      ischaemia for 4 h, followed by different reperfusion periods. The animals were
      divided in four groups: control; 4 h of ischaemia (IR); 4 h of ischaemia plus 1 h
      reperfusion (IR-1 h); 4 h of ischaemia plus 24 h reperfusion (IR-24 h); and 4 h
      of ischaemia plus 72 h reperfusion (IR-72 h). At the end of the procedures,
      samples of soleus muscle were collected and frozen in n-hexane at -70 degrees C.
      Cryostat sections were submitted to haematoxylin-eosin, succinate dehydrogenase
      (SDH) and nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR)
      stains. An additional muscle sample was processed for electron microscopy. No
      alterations were found in control animals. IR group showed fibres had normal
      aspect besides some round, acidophilic and hypertrophic fibres. There were
      several fibres with angular outlines and smaller diameters in this group compared
      with control group. NADH-TR/SDH reaction was moderately intense in most fibres.
      In some fibres, cytoplasm showed areas without activity and other fibres had very
      intense reactivity. IR-1 h group showed oedema hypercontracted fibres with
      disorganized myofibrils, mitochondria with focal lesions and dilated sarcoplasmic
      reticulum. NADH-TR/SDH reaction was moderate to weak. IR-24 h showed intense
      inflammatory infiltrate in the endomysium and perimysium. NADH-TR/SDH reaction
      was similar to IR-1 h. IR-72 h showed necrotic fibres, areas with inflammatory
      infiltrate, reduced muscle fibres at different stages of necrosis and
      phagocytosis, and many small round and basophilic fibres characterizing a
      regeneration process. NADH-TR/SDH reaction was weak to negative. Our results
      suggest that ischaemia and the subsequent 1-, 24- and 72-h reperfusions induced
      progressive histological damage. Although progressive, it may be reversible
      because there were ultrastructural signs of recovery after 72-h reperfusion. This
      recovery could in part be due to the low oxidative stress identified by the
      morphological and histochemical analysis.

PMID- 17504445
TI  - Differential inflammatory mediator response in vitro from murine macrophages to
      lactobacilli and pathogenic intestinal bacteria.
AB  - Chronic active colitis (including inflammatory bowel disease - IBD) is maintained
      by a variety of pro-inflammatory mediators. Certain intestinal bacterial strains
      may induce colitis, whereas some strains (e.g. Lactobacillus spp.) show a
      protective effect in colitis owing to their anti-inflammatory activity. In this
      study, we have examined the production of selected inflammatory cytokines,
      reactive oxygen species (ROS), nitric oxide (NO) and the expression of haeme
      oxygenase-1 (HO-1) by murine peritoneal macrophages stimulated in vitro by the
      intestinal bacterial strains, isolated from mice with colitis. Lactobacillus
      strains (Lactobacillus reuteri, L. johnsonii, L. animalis/murinus) and two
      potentially pathogenic bacteria (Escherichia coli and Enterococcus faecalis)
      induced the production of substantial amounts of cytokines with a strain specific
      profile. Despite some interstrain differences, all lactobacilli induced
      production of anti-inflammatory cytokines (IL-10(high), IL-6(low), IL
      12p70(low)). Conversely, E. faecalis and E. coli induced the production of
      proinflammatory cytokines (TNF-alpha, IL-12p70), the cytokines essential for
      chronic IBD. Macrophages released comparably substantial amounts of ROS in
      response to all Lactobacillus strains tested, while E. coli and E. faecalis
      ability to induce generation of ROS was negligible. In contrast to ROS, the
      production of NO/NO(2) (-) by macrophages activated with all bacterial strains
      tested was similar. Moreover, for the first time, it has been shown that
      intestinal bacteria differed in their ability to induce expression of HO-1, a
      stress-inducible enzyme with antioxidant and anti-inflammatory properties. The
      beneficial immunoregulatory properties of candidate probiotic bacteria for the
      treatment of IBD are discussed.

PMID- 17504446
TI  - Hormonal and morphological study of the pituitaries in reeler mice.
AB  - Reelin is a neuronal glycoprotein that plays a crucial role in brain layer
      formation during prenatal development. The reeler mutant mouse lacks Reelin,
      leading to abnormalities in the neuronal layering of cerebral cortex and
      cerebellum, producing ataxia, tremor and abnormal locomotion. Reeler mice are
      reported to have growth retardation and most of them are sterile or unable to
      bring up their newborns. Since the brain is one of the main regulator of
      pituitary hormone secretion and no information was reported regarding pituitary
      function and structure in these mutant mice, we studied pituitary endocrine
      activity and morphology in reeler mice. Mice were classified in three groups as
      reeler homozygote (RHM), reeler heterozygote (RHT) or control (CO). Pituitary
      hormone blood levels were assessed by enzyme immunoassay (EIA) and
      immunoradiometric assay (IRMA). Animals and their pituitaries were weighted and
      pituitaries were studied by histology, immunohistochemistry and electron
      microscopy. Results showed statistically significant differences in body weight
      and in adrenocorticotropic hormone (ACTH) and luteinizing hormone (LH) blood
      levels between the three groups. In contrast, growth hormone (GH) blood levels
      showed a high individual variation and no decrease in reeler groups compared with
      CO. Morphological studies revealed no differences in pituitary cell types except
      that somatotrophs appeared to be slightly smaller in RHM and RHT. Although it
      seems that pituitary hypofunction is not responsible for growth retardation, more
      studies are needed to obtain a deeper insight into the endocrine status of these
      mutant mice to elucidate the cause of their low body weight and reproductive
      behaviour.

PMID- 17504448
TI  - Cellular morphological parameters of the human urinary bladder (malignant and
      normal).
AB  - The normal and malignant cellular morphological parameters (intra- and
      extracellular spaces of the human urinary bladder) were obtained from analysis of
      digital images of bladder histology sections. Then these cellular morphological
      parameters were compared with the same parameters obtained from the literature
      for the bladder tissue. However, the limited quantitative data about these
      parameters available in the literature for bladder cell sizes and other
      geometrical parameters such as extra-cellular space does not provide a scientific
      basis to construct accurate structural models of normal and malignant bladder
      tissue. Therefore, there is usually no quantitative discussion of cell sizes in
      literature but the measured data in this work can provide a reasonable estimation
      of expected morphological parameter changes of bladder tissue with pathology. To
      produce this quantitative information, and also, to build a suitable models in
      another study using electrical properties of the tissue, 10 digital images of
      histological sections of normal, and six sections from malignant areas of the
      human urinary bladder, were chosen randomly (ex vivo). Finally, the measured data
      showed that there is a significant difference between the cell dimensions (in
      basal and intermediate layers) of normal and malignant bladder tissues.

PMID- 17504447
TI  - Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and
      p53) in lymph node and liver metastases of gastric cancer.
AB  - PURPOSE: Metastasis remains an incurable common complication in patients with
      gastric cancer. A variety of theories have been proposed to explain the
      inefficiency of the metastatic process. To compare protein expression of
      metastasis-related genes (nm23, KISS1, KAI1 and p53) between primary tumours and
      metastatic tumours may be useful in illustrating these theories. METHODS:
      Metastasis-related tissue microarrays (including normal tissues, primary tumours,
      nodal metastases and liver metastases) were constructed. The protein expression
      of nm23, KISS1, KAI1 and p53 in lymph node and liver metastases from advanced
      gastric cancer specimens was mainly examined by immunohistochemical staining in
      relation to primary tumours. RESULTS: Immunohistochemical staining showed reduced
      protein expression of nm23, KISS1 and KAI1 in lymph node and liver metastases
      compared with primary tumours. Results for p53 were to the contrary. CONCLUSIONS:
      Our investigations revealed a tendency of reduced protein expression of
      metastasis suppressor genes nm23, KISS1 and KAI1 in gastric cancer with the
      progress of metastasis. This means that the progression theory is an important
      determinant of metastatic efficiency.

PMID- 17504451
TI  - New Phytologist on plant evolution.

PMID- 17504449
TI  - Pleomorphic adenoma and adenoid cystic carcinoma: in vitro study of the impact of
      TGFbeta1 on the expression of integrins and cytoskeleton markers of cell
      differentiation.
AB  - Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) are the commonest
      benign and malignant salivary gland tumours respectively. Interactions between
      cells and extracellular matrix of PA and ACC, partially mediated by integrins,
      are important in their biology. The expression of integrins is regulated by
      numerous factors, amongst them, transforming growth factor beta1 (TGFbeta1). Our
      study investigated the effects of TGFbeta1 on the expression of integrin beta
      subunits in vitro and on the expression of cytoskeletal proteins of cells derived
      from PA and ACC. The expression of cytoskeletal differentiation markers and
      integrins was assessed using immunofluorescence. ELISA assays were employed to
      quantitate the expression integrins and MTT assays evaluated the mitochondrial
      activity of cells stimulated with TGFbeta1. PA cells showed increased expression
      of integrins and de novo expression of differentiation markers upon TGFbeta1
      stimulation. ACC cells were less responsive to such stimulation. This may reflect
      important differences in the biological behaviour of benign and malignant cells.

PMID- 17504452
TI  - What are the mechanisms and specificity of mycorrhization helper bacteria?

PMID- 17504453
TI  - Forest genomics grows up and branches out.

PMID- 17504454
TI  - Fungal and oomycete genes galore.

PMID- 17504455
TI  - Polyploidy: genome obesity and its consequences.

PMID- 17504456
TI  - Tracks for traffic: microtubules in the plant pathogen Ustilago maydis.
AB  - Pathogenic development of the corn smut fungus Ustilago maydis depends on the
      ability of the hypha to grow invasively. Extended hyphal growth and mitosis
      require microtubules, as revealed by recent studies on the microtubule
      cytoskeleton. Surprisingly, hyphal tip growth involves only two out of 10
      kinesins. Kinesin-3 is responsible for tip-directed (anterograde) endosome
      motility of early endosomes, which are thought to support hyphal elongation by
      apical membrane recycling. In addition, kinesin-3, together with kinesin-1 and
      myosin-5, appear to deliver secretory vesicles to the hyphal tip. Kinesin-1 also
      affects endosome motility by targeting cytoplasmic dynein to microtubule plus
      ends. This plus-end localization of dynein is essential for cell body-directed
      (retrograde) endosome motility, but also allows force generation during spindle
      elongation in mitosis. Furthermore, kinesin-1 and dynein participate in the
      organization of the microtubule array, thereby building their own network of
      tracks for intracellular motility. The recent progress in understanding
      microtubule-based processes in U. maydis has revealed an unexpected complexity of
      motor functions essential for the virulence of this pathogen. Further studies on
      structural and regulatory requirements for motor activity should help identify
      novel targets for fungicide development.

PMID- 17504457
TI  - A new role for phytochromes in temperature-dependent germination.
AB  - Germination timing is a fundamental life-history trait, as seedling establishment
      predicates realized fitness in the wild. Light and temperature are two important
      cues by which seeds sense the proper season of germination. Using Arabidopsis
      thaliana, we provide evidence that phytochrome-mediated germination pathways
      simultaneously respond to light and temperature cues in ways that affect
      germination. Phytochrome mutant seeds were sown on agar plates and allowed to
      germinate in lit, growth chambers across a range of temperatures (7 degrees C to
      28 degrees C). phyA had an important role in promoting germination at warmer
      temperatures, phyE was important to germination at colder temperatures and phyB
      was important to germination across a range of temperatures. Different
      phytochromes were required for germination at different temperatures, indicating
      a restriction or even a potential specialization of individual phytochrome
      activity as a function of temperature. This temperature-dependent activity of
      particular phytochromes reveals a potentially novel role for phytochrome pathways
      in regulating the seasonal timing of germination.

PMID- 17504458
TI  - Reactive oxygen species produced by NADPH oxidase are involved in pollen tube
      growth.
AB  - Tip-localized reactive oxygen species (ROS) were detected in growing pollen tubes
      by chloromethyl dichlorodihydrofluorescein diacetate oxidation, while tip
      localized extracellular superoxide production was detected by nitroblue
      tetrazolium (NBT) reduction. To investigate the origin of the ROS we cloned a
      fragment of pollen specific tobacco NADPH oxidase (NOX) closely related to a
      pollen specific NOX from Arabidopsis. Transfection of tobacco pollen tubes with
      NOX-specific antisense oligodeoxynucleotides (ODNs) resulted in decreased amount
      of NtNOX mRNA, lower NOX activity and pollen tube growth inhibition. The ROS
      scavengers and the NOX inhibitor diphenylene iodonium chloride (DPI) inhibited
      growth and ROS formation in tobacco pollen tube cultures. Exogenous hydrogen
      peroxide (H2O2) rescued the growth inhibition caused by NOX antisense ODNs.
      Exogenous CaCl2 increased NBT reduction at the pollen tube tip, suggesting that
      Ca2+ increases the activity of pollen NOX in vivo. The results show that tip
      localized ROS produced by a NOX enzyme is needed to sustain the normal rate of
      pollen tube growth and that this is likely to be a general mechanism in the
      control of tip growth of polarized plant cells.

PMID- 17504459
TI  - Spatio-temporal leaf growth patterns of Arabidopsis thaliana and evidence for
      sugar control of the diel leaf growth cycle.
AB  - Leaf growth dynamics are driven by diel rhythms. The analysis of spatio-temporal
      leaf growth patterns in Arabidopsis thaliana wild type and mutants of interest is
      a promising approach to elucidate molecular mechanisms controlling growth. The
      diel availability of carbohydrates is thought to affect diel growth. A digital
      image sequence processing (DISP)-based noninvasive technique for visualizing and
      quantifying highly resolved spatio-temporal leaf growth was adapted for the model
      plant A. thaliana. Diel growth patterns were analysed for the wild type and for a
      mutant with altered diel carbohydrate metabolism. A. thaliana leaves showed
      highest relative growth rates (RGRs) at dawn and lowest RGRs at the beginning of
      the night. Along the lamina, a clear basipetal gradient of growth rate
      distribution was found, similar to that in many other dicotyledonous species. The
      starch-free 1 (stf1) mutant revealed changed temporal growth patterns with
      reduced nocturnal, and increased afternoon, growth activity. The established DISP
      technique is presented as a valuable tool to detect altered temporal growth
      patterns in A. thaliana mutants. Endogenous changes in the diel carbohydrate
      availability of the starch-free mutant clearly affected its diel growth rhythms.

PMID- 17504460
TI  - Metabolite profiling of Douglas-fir (Pseudotsuga menziesii) field trials reveals
      strong environmental and weak genetic variation.
AB  - The primary objective of this study was to assess metabolomics for its capacity
      to discern biological variation among 10 full-sib families of a Douglas-fir tree
      breeding population, replicated on two sites. The differential accumulation of
      small metabolites in developing xylem was examined through metabolite profiles
      (139 metabolites common to 181 individual trees) generated by gas chromatography
      mass spectrometry and a series of statistical analyses that incorporated family,
      site, and tree growth and quantitative phenotypic wood traits (wood density,
      microfibril angle, wood chemistry and fiber morphology). Multivariate
      discriminant, canonical discriminant and factor analyses and broad-sense
      heritabilities revealed that metabolic and phenotypic traits alike were strongly
      related to site, while similar associations relating to genetic (family)
      structure were weak in comparison. Canonical correlation analysis subsequently
      identified correlations between specific phenotypic traits (i.e. tree growth,
      fibre morphology and wood chemistry) and metabolic traits (i.e. carbohydrate and
      lignin biosynthetic metabolites), demonstrating a coherent relationship between
      genetics, metabolism, environmental and phenotypic expression in wood-forming
      tissue. The association between cambial metabolites and tree phenotype, as
      revealed by metabolite profiling, demonstrates the value of metabolomics for
      systems biology approaches to understanding tree growth and secondary cell wall
      biosynthesis in plants.

PMID- 17504461
TI  - Vascular architecture in shoots of early divergent vascular plants, Lycopodium
      clavatum and Lycopodium annotinum.
AB  - Lycopodium represents a phylogenetically distinct clade of basal vascular plants
      with anatomical characters that have no parallel in other lineages. Thus,
      knowledge of lycopod structure and development may reveal important information
      about the common ancestors of all vascular plants. Here we report the unique
      architecture of the conducting system in Lycopodium annotinum and Lycopodium
      clavatum. Based on multiple series of anatomical sections, we reconstructed
      spatial relationships between microphylls and the stelar system. Analysis
      revealed that protoxylem ribs (PXR) were vertical, regardless of type of
      phyllotaxis, and their numbers were variable. Microphyll traces (MTr) were
      randomly distributed between ribs, resulting in the absence of defined sympodia
      and varied lengths of MTr. Dichotomous branching contributed to additional
      features, for example occurrence of mesarch protoxylem, affecting stele structure
      and PXR numbers. Our data showed limited interrelationships between lycopod
      vasculature and microphyll phyllotaxis. This may suggest that both systems
      developed independently, then evolved together to form the integrated supply
      system. Thus vasculature in extant lycophytes may be less functionally efficient
      than in seed plants, where consistent leaf-trace lengths guarantee predictable
      energy utilization during ontogeny. Differences may result from the
      phylogenetically different origin of microphylls, and the level of vascular
      complexity.

PMID- 17504462
TI  - Relationships among xylem transport, biomechanics and storage in stems and roots
      of nine Rhamnaceae species of the California chaparral.
AB  - Here, hypotheses about stem and root xylem structure and function were assessed
      by analyzing xylem in nine chaparral Rhamnaceae species. Traits characterizing
      xylem transport efficiency and safety, mechanical strength and storage were
      analyzed using linear regression, principal components analysis and phylogenetic
      independent contrasts (PICs). Stems showed a strong, positive correlation between
      xylem mechanical strength (xylem density and modulus of rupture) and xylem
      transport safety (resistance to cavitation and estimated vessel implosion
      resistance), and this was supported by PICs. Like stems, greater root cavitation
      resistance was correlated with greater vessel implosion resistance; however,
      unlike stems, root cavitation resistance was not correlated with xylem density
      and modulus of rupture. Also different from stems, roots displayed a trade-off
      between xylem transport safety from cavitation and xylem transport efficiency.
      Both stems and roots showed a trade-off between xylem transport safety and xylem
      storage of water and nutrients, respectively. Stems and roots differ in xylem
      structural and functional relationships, associated with differences in their
      local environment (air vs soil) and their primary functions.

PMID- 17504463
TI  - Photosynthetic performance and water relations in young pubescent oak (Quercus
      pubescens) trees during drought stress and recovery.
AB  - The capability to withstand and to recover from severe summer droughts is
      becoming an important issue for tree species in central Europe, as dry periods
      are predicted to occur more frequently over the coming decades. Changes in leaf
      gas exchange, chlorophyll a fluorescence and leaf compounds related to
      photoprotection were analysed in young Quercus pubescens trees under field
      conditions during two summers (2004 and 2005) of progressive drought and
      subsequent rewatering. Photochemistry was reversibly down-regulated and
      dissipation of excess energy was enhanced during the stress phase, while contents
      of leaf pigments and antioxidants were almost unaltered. Plant water status was
      restored immediately after rewatering. Net photosynthesis (P(n)) measured at
      ambient CO2 recovered from inhibition by drought within 4 wk. P(n) measured at
      elevated CO2--to overcome stomatal limitations--was restored after a few days. A
      network of photoprotective mechanisms acted in preserving the potential
      functionality of the photosynthetic apparatus during severe drought, leading to a
      rapid recovery of photosynthetic activity after rewatering. Thus, Q. pubescens
      seems to be capable of withstanding and surviving extreme drought events.

PMID- 17504464
TI  - Optimal nitrogen allocation controls tree responses to elevated CO2.
AB  - Despite the abundance of experimental data, understanding of forest responses to
      elevated CO2 is limited. Here I show that a key to previously unexplained
      production and leaf area responses lies in the interplay between whole-plant
      nitrogen (N) allocation and leaf photosynthesis. A simple tree growth model,
      controlled by net growth maximization through optimization of leaf area index
      (LAI) and plant N, is used to analyse CO2 responses in both young, expanding and
      closed, steady-state canopies. The responses are sensitive to only two
      independent parameters, the photosynthetic capacity per leaf N (a) and the fine
      root N:leaf N ratio. The model explains observed CO2 responses of photosynthesis,
      production and LAI in four forest free air CO2 enrichment (FACE) experiments.
      Insensitivity of LAI except at low LAI, increase in light-use efficiency, and
      photosynthetic down-regulation (as a result of reduced leaf N per area) at
      elevated CO2 are all explained through the combined effects on a and leaf quantum
      efficiency. The model bridges the gap between the understanding of leaf-level and
      plant-level responses and provides a transparent framework for interpreting and
      linking structural (LAI) and functional (net primary production (NPP):gross
      primary production (GPP) ratio, light-use efficiency, photosynthetic down
      regulation) responses to elevated CO2.

PMID- 17504465
TI  - Projected ecosystem impact of the Prairie Heating and CO2 Enrichment experiment.
AB  - The Prairie Heating and CO2 Enrichment (PHACE) experiment has been initiated at a
      site in southern Wyoming (USA) to simulate the impact of warming and elevated
      atmospheric CO2 on ecosystem dynamics for semiarid grassland ecosystems. The
      DAYCENT ecosystem model was parametrized to simulate the impact of elevated CO2
      at the open-top chamber (OTC) experiment in north-eastern Colorado (1996-2001),
      and was also used to simulate the projected ecosystem impact of the PHACE
      experiments during the next 10 yr. Model results suggest that soil water content,
      plant production, soil respiration, and nutrient mineralization will increase for
      the high-CO2 treatment. Soil water content will decrease for all years, while
      nitrogen mineralization, soil respiration, and plant production will both
      decrease and increase under warming depending on yearly differences in water
      stress. Net primary production (NPP) will be greatest under combined warming and
      elevated CO2 during wet years. Model results are consistent with empirical field
      data suggesting that water and nitrogen will be critical drivers of the semiarid
      grassland response to global change.

PMID- 17504466
TI  - Irrigation and enhanced soil carbon input effects on below-ground carbon cycling
      in semiarid temperate grasslands.
AB  - Global climate change is generally expected to increase net primary production,
      resulting in increased soil carbon (C) inputs. To gain an understanding of how
      such increased soil C inputs would affect C cycling in the vast grasslands of
      northern China, we conducted a field experiment in which the responses of plant
      and microbial biomass and respiration were studied. Our experiment included the
      below-ground addition of particulate organic matter (POM) at rates equivalent to
      0, 60, 120 and 240 g C m(-2), under either natural precipitation or under
      enhanced precipitation during the summer period (as predicted for that region in
      recent simulations using general circulation models). We observed that addition
      of POM had a large effect on soil microbial biomass and activity and that a major
      part of the added C was rapidly lost from the system. This suggests that
      microbial activity in the vast temperate grassland ecosystems of northern China
      is energy-limited. Moreover, POM addition (and the associated nutrient release)
      affected plant growth much more than the additional water input. Although we
      performed no direct fertilization experiments, the response of plant productivity
      to POM addition (and associated release of nutrients) leads us to believe that
      plant productivity in the semiarid grassland ecosystems of northern China is
      primarily limited by nutrients and not by water.

PMID- 17504467
TI  - Ectomycorrhizal community structure in a xeric Quercus woodland based on rDNA
      sequence analysis of sporocarps and pooled roots.
AB  - Quercus woodlands are key components of California's wild landscapes, yet little
      is known about ectomycorrhizal (EM) fungi in these ecosystems. We examined the EM
      community associated with Quercus douglasii using sporocarp surveys and by
      pooling EM roots and subjecting them to DNA extraction, polymerase chain reaction
      (PCR), cloning, restriction fragment length polymorphism (RFLP) screening and DNA
      sequencing. Ectomycorrhizal root symbionts were sampled four times in 2003-04.
      During this time, the below-ground community structure was relatively stable; we
      found no evidence of taxa adapted to winter or spring conditions and only one
      species varied widely in occurrence between years. The EM community from
      sporocarps and roots was diverse (161 species), rich in Ascomycota (46 species),
      and dominated by fungi with cryptic sporocarps. This included a large number of
      resupinate and hypogeous taxa, many of which were detected both above- and below
      ground.

PMID- 17504468
TI  - Sebacinales are common mycorrhizal associates of Ericaceae.
AB  - Previous reports of sequences of Sebacinales (basal Hymenomycetes) from ericoid
      mycorrhizas raised the question as to whether Sebacinales are common mycorrhizal
      associates of Ericaceae, which are usually considered to associate with
      ascomycetes. Here, we sampled 239 mycorrhizas from 36 ericoid mycorrhizal species
      across the world (Vaccinioideae and Ericoideae) and 361 mycorrhizas from four
      species of basal Ericaceae lineages (Arbutoideae and Monotropoideae) that do not
      form ericoid mycorrhizas, but ectendomycorrhizas. Sebacinales were detected using
      sebacinoid-specific primers for nuclear 28S ribosomal DNA, and some samples were
      investigated by transmission electron microscopy (TEM). Diverging Sebacinales
      sequences were recovered from 76 ericoid mycorrhizas, all belonging to
      Sebacinales clade B. Indeed, some intracellular hyphal coils had ultrastructural
      TEM features expected for Sebacinales, and occurred in living cells. Sebacinales
      belonging to clade A were found on 13 investigated roots of the basal Ericaceae,
      and TEM revealed typical ectendomycorrhizal structures. Basal Ericaceae lineages
      thus form ectendomycorrhizas with clade A Sebacinales, a clade that also harbours
      ectomycorrhizal fungi. This further supports the proposition that Ericaceae
      ectendomycorrhizas involve ectomycorrhizal fungal taxa. When ericoid mycorrhizas
      evolved secondarily in Ericaceae, a shift of mycobionts occurred to ascomycetes
      and clade B Sebacinales, hitherto not described as ericoid mycorrhizal fungi.

PMID- 17504469
TI  - Trehalose turnover during abiotic stress in arbuscular mycorrhizal fungi.
AB  - Trehalose is a common reserve carbohydrate in fungi, whose role has been recently
      extended to other cellular functions, such as stress tolerance, glycolysis
      control, sporulation and infectivity of some pathogenic strains. To gain some
      insight into the role of trehalose during abiotic stress in arbuscular
      mycorrhizal (AM) fungi, we assessed trehalose content as well as transcriptional
      regulation and enzyme activity of neutral trehalase and trehalose-6-phosphate
      phosphatase in Glomus intraradices in response to heat shock, chemical or osmotic
      stress. Prolonged or intensive exposure to heat or chemical stress, but not
      osmotic stress, caused an increase of trehalose in the cell. We found this
      associated with transient up-regulation of the trehalose-6-P phosphatase (GiTPS2)
      transcript that coincided with moderate increases in enzyme activity. By
      contrast, there were no changes in neutral trehalase (GiNTH1) RNA accumulation in
      response to stress treatments, while they promoted, in most cases, an increase in
      activity. After stress had ceased, trehalose returned to basal concentrations,
      pointing to a role of neutral trehalase activity in heat shock recovery. A yeast
      complementation assay confirmed the role of neutral trehalase in thermotolerance.
      Taken together, these results indicate that trehalose could play a role in AM
      fungi during the recovery from certain stresses such as heat shock and chemical
      treatment.

PMID- 17504470
TI  - Suppression of plant defence response by a mycorrhiza helper bacterium.
AB  - The aim of the present study was to determine whether the mycorrhiza helper
      bacterium Streptomyces sp. AcH 505 could serve as a biocontrol agent against
      Heterobasidion root and butt rot. Bacterial influence on mycelial growth of
      Heterobasidion sp. isolates, on the colonization of wood discs and Norway spruce
      (Picea abies) roots was determined. The effect of AcH 505 on plant
      photosynthesis, peroxidase activity and gene expression, and needle infections
      were investigated. AcH 505 was antagonistic to 11 of 12 tested fungal
      Heterobasidion isolates. The antagonism resulted in a suppression of fungal
      colonization of Norway spruce roots and wood discs. Mycelial growth rate of the
      12th strain, Heterobasidion abietinum 331 was not affected by AcH 505, and
      colonization of roots by this fungal strain was promoted by AcH 505. Bacterial
      inoculation led to decreased peroxidase activities and gene expression levels in
      roots. AcH 505 promotes plant root colonization by Heterobasidion strains that
      are tolerant to antifungal metabolites produced by the bacterium. This may result
      from unknown bacterial factors that suppress the plant defence response.

PMID- 17504471
TI  - Spatial scale of local adaptation and population genetic structure in a miniature
      succulent, Argyroderma pearsonii.
AB  - Explicit understanding of the spatial scale of evolutionary processes is required
      in order to set targets for their effective conservation. Here, we explore the
      spatial context of neutral and adaptive divergence in the species-rich
      Knersvlakte region of South Africa. Specifically, we aimed to assess the
      importance of erosional drainage basins as spatial units of evolutionary process.
      We used amplified fragment length polymorphism (AFLP) and reciprocal transplants
      to investigate genetic differentiation in Argyroderma pearsonii, sampled from
      sparse and dense quartz habitats within each of three drainage basins. This
      design allowed assessment of differentiation at two distinct spatial scales;
      between habitats within basins, and between basins. We found near-perfect
      concordance between genetic clusters and basin occupancy, suggesting restricted
      interbasin gene flow. In addition, transplants reveal adaptive divergence between
      basins on the dense quartz habitat. We have shown that neutral and adaptive
      differentiation occurs between basins, but not between habitats within basins,
      suggesting that conservation plans aimed at conserving multiple interconnected
      drainage basins will capture an important axis of evolutionary process on the
      Knersvlakte.

PMID- 17504472
TI  - Small populations are mate-poor but pollinator-rich in a rare, self-incompatible
      plant, Hymenoxys herbacea (Asteraceae).
AB  - If pollinators or compatible mates are scarce, plants in small populations may be
      pollen-limited and consequently produce fewer offspring. However, determining the
      relative importance of the genetic vs ecological mechanisms limiting successful
      pollination is challenging. We explored the relationships among population size,
      population connectivity, pollinator visitation, allozyme diversity, mate
      availability (measured as percent compatible crosses among plants within a
      population), and pollen limitation in 12 populations (N = 39-885,274) of the self
      incompatible plant Hymenoxys herbacea in Ontario, Canada. Unexpectedly, small
      populations had more insect flower visitors per capitulum than large populations.
      Consistent with the effects of genetic drift, both allozyme polymorphism and mate
      availability decreased with decreasing population size. Pollen limitation was low
      and significant in only one population and could not be predicted based on
      knowledge of population size, connectivity, compatible mate availability, or
      pollinator visitation. Population size had detectable effects on both pollinator
      activity and mate availability. However, because the effect of population size
      was complementary on these two potentially limiting mechanisms, this threatened
      plant was rarely pollen-limited.

PMID- 17504473
TI  - Linear chromosomes in bacteria: no straight edge advantage?

PMID- 17504474
TI  - Sponge disease: a global threat?
AB  - Sponges are the most simple and primitive metazoans, yet they have various
      biological and ecological properties that make them an influential component of
      coral-reef ecosystems. Marine sponges provide refuge for many small invertebrates
      and are critical to benthic-pelagic coupling across a wide range of habitats.
      Reports of sponge disease have increased dramatically in recent years with sponge
      populations decimated throughout the Mediterranean and Caribbean. Reports also
      suggest an increased prevalence of sponge disease in Papua New Guinea, the Great
      Barrier Reef and in the reefs of Cozumel, Mexico. These epidemics can have severe
      impacts on the survival of sponge populations, the ecology of the reef and the
      fate of associated marine invertebrates. Despite the ecological and commercial
      importance of sponges, the understanding of sponge disease is limited. There has
      generally been a failure to isolate and identify the causative agents of sponge
      disease, with only one case confirming Koch's postulates and identifying a novel
      Alphaproteobacteria strain as the primary pathogen. Other potential disease
      agents include fungi, viruses, cyanobacteria and bacterial strains within the
      Bacillus and Pseudomonas genera. There is some evidence for correlations between
      sponge disease and environmental factors such as climate change and
      urban/agricultural runoff. This review summarizes the occurrence of sponge
      disease, describes the syndromes identified thus far, explores potential linkages
      with environmental change and proposes a strategy for future research towards
      better management of sponge disease outbreaks.

PMID- 17504475
TI  - Ecological dynamics of the bivalve-killing dinoflagellate Heterocapsa
      circularisquama and its infectious viruses in different locations of western
      Japan.
AB  - We studied the ecological relationships between the bloom-forming dinoflagellate
      Heterocapsa circularisquama and its infectious viruses in field surveys conducted
      in western Japan. The occurrence of H. circularisquama blooms in Imari Bay during
      2002 and in Ago Bay during 2002 and 2004 was accompanied by specific increase in
      abundance of viruses lytic to H. circularisquama. Using northern dot-blot
      analysis, approximately 96% of the clonal virus isolates collected in the field
      surveys positively reacted with a molecular probe specific for HcRNAV (H.
      circularisquama RNA virus); hence, viral impacts on H. circularisquama population
      observed in these field surveys are considered largely due to HcRNAV and/or its
      closely related viruses. The dynamics of type UA viruses and type CY viruses
      having complementary host ranges to H. circularisquama clones were different in
      each survey and considered to reflect fluctuations in abundance of their suitable
      host cells in situ. The dynamics of H. circularisquama and its viruses in Ago Bay
      from 2002 to 2004 suggests the concentration of HcRNAV in the sediment prior to
      the host's blooming season is a significant factor in determining the size and
      length of the H. circularisquama blooms. These results support the hypothesis
      that HcRNAV infection is one of the significant factors affecting the population
      dynamics of H. circularisquama in both quantity (biomass) and quality (clonal
      composition).

PMID- 17504476
TI  - Effect of salinity changes on the bacterial diversity, photosynthesis and oxygen
      consumption of cyanobacterial mats from an intertidal flat of the Arabian Gulf.
AB  - The effects of salinity fluctuation on bacterial diversity, rates of gross
      photosynthesis (GP) and oxygen consumption in the light (OCL) and in the dark
      (OCD) were investigated in three submerged cyanobacterial mats from a transect on
      an intertidal flat. The transect ran 1 km inland from the low water mark along an
      increasingly extreme habitat with respect to salinity. The response of GP, OCL
      and OCD in each sample to various salinities (65 per thousand, 100 per thousand,
      150 per thousand and 200 per thousand) were compared. The obtained sequences and
      the number of unique operational taxonomic units showed clear differences in the
      mats' bacterial composition. While cyanobacteria decreased from the lower to the
      upper tidal mat, other bacterial groups such as Chloroflexus and
      Cytophaga/Flavobacteria/Bacteriodetes showed an opposite pattern with the highest
      dominance in the middle and upper tidal mats respectively. Gross photosynthesis
      and OCL at the ambient salinities of the mats decreased from the lower to the
      upper tidal zone. All mats, regardless of their tidal location, exhibited a
      decrease in areal GP, OCL and OCD rates at salinities > 100 per thousand. The
      extent of inhibition of these processes at higher salinities suggests an increase
      in salt adaptation of the mats microorganisms with distance from the low water
      line. We conclude that the resilience of microbial mats towards different
      salinity regimes on intertidal flats is accompanied by adjustment of the
      diversity and function of their microbial communities.

PMID- 17504477
TI  - Cross-resistance spectra of Culex quinquefasciatus resistant to mosquitocidal
      toxins of Bacillus thuringiensis towards recombinant Escherichia coli expressing
      genes from B. thuringiensis ssp. israelensis.
AB  - Sixteen Escherichia coli clones were assayed against susceptible and Bacillus
      thuringiensis-resistant Culex quinquefasciatus larvae. The clones expressed
      different combinations of four genes from Bacillus thuringiensis ssp.
      israelensis; three genes encoded mosquitocidal toxins (Cry11Aa, Cry4Aa and
      Cyt1Aa) and the fourth encoded an accessory protein (P20). The cross-resistance
      spectra of the mosquitoes were similar to the profiles for recombinant B.
      thuringiensis strains expressing B. thuringiensis toxin genes, but with varied
      toxicity levels. The toxicity of the recombinants towards resistant mosquito
      larvae was improved when p20 and cyt1Aa were expressed in combination with cry4Aa
      and/or cry11Aa. Recombinant pVE4-ADRC, expressing cry4Aa, cry11Aa, p20 and
      cyt1Aa, was the most active against the resistant Culex, and resistance levels
      did not exceed fourfold. These results indicate that B. thuringiensis ssp.
      israelensis genes expressed in a heterologous host such as E. coli can be
      effective against susceptible and B. thuringiensis-resistant larvae and suppress
      resistance.

PMID- 17504478
TI  - Extremely acidic, pendulous cave wall biofilms from the Frasassi cave system,
      Italy.
AB  - The sulfide-rich Frasassi cave system hosts an aphotic, subsurface microbial
      ecosystem including extremely acidic (pH 0-1), viscous biofilms (snottites)
      hanging from the cave walls. We investigated the diversity and population
      structure of snottites from three locations in the cave system using full cycle
      rRNA methods and culturing. The snottites were composed primarily of bacteria
      related to Acidithiobacillus species. Other populations present in the snottites
      included Thermoplasmata group archaea, bacteria related to Sulfobacillus,
      Acidimicrobium, and the proposed bacterial lineage TM6, protists, and filamentous
      fungi. Based on fluorescence in situ hybridization population counts,
      Acidithiobacillus are key members of the snottite communities, accompanied in
      some cases by smaller numbers of archaea related to Ferroplasma and other
      Thermoplasmata. Diversity estimates show that the Frasassi snottites are among
      the lowest-diversity natural microbial communities known, with one to six
      prokaryotic phylotypes observed depending on the sample. This study represents
      the first in-depth molecular survey of cave snottite microbial diversity and
      population structure, and contributes to understanding of rapid limestone
      dissolution and cave formation by microbially mediated sulfuric acid
      speleogenesis.

PMID- 17504479
TI  - Coupling between autocatalytic cell death and transparent exopolymeric particle
      production in the marine cyanobacterium Trichodesmium.
AB  - Extracellular polysaccharide aggregates, operationally defined as transparent
      exopolymeric particles (TEP), are recognized as an important conduit for carbon
      recycling and export in aquatic systems. Yet, the factors controlling the build
      up of the TEP pool are not well characterized. Here we show that increased TEP
      production by Trichodesmium, an oceanic bloom-forming nitrogen-fixing
      (diazotrophic) cyanobacterium, is coupled with autocatalytic programmed cell
      death (PCD) process. We demonstrate that PCD induction, in both laboratory
      cultures and natural populations, is characterized by high caspase-like activity,
      correlates with enhanced TEP production, and occurs under iron and phosphorus
      starvation, as well as under high irradiance and oxidative stress. Enhanced TEP
      production was not observed in actively growing populations. We provide further
      evidence that iron is a key trigger for the induction of PCD. We demonstrate, for
      the first time, the concomitant enhanced build-up of the TEP pool when
      Trichodesmium is Fe-stressed. These results suggest a functional linkage between
      activation of caspases and PCD in Trichodesmium and regulation of vertical carbon
      and nitrogen fluxes. We hypothesize that modulation of TEP formation and its
      qualities by different mortality pathways could regulate the fate of
      phytoplankton blooms and particulate organic matter in aquatic ecosystems.

PMID- 17504480
TI  - Diversity, relative abundance and metabolic potential of bacterial endosymbionts
      in three Bathymodiolus mussel species from cold seeps in the Gulf of Mexico.
AB  - Cold seeps in the Gulf of Mexico are often dominated by mussels of the genus
      Bathymodiolus that harbour symbiotic bacteria in their gills. In this study, we
      analysed symbiont diversity, abundance and metabolic potential in three mussel
      species from the northern Gulf of Mexico: Bathymodiolus heckerae from the West
      Florida Escarpment, Bathymodiolus brooksi from Atwater Valley and Alaminos
      Canyon, and 'Bathymodiolus' childressi, which co-occurs with B. brooksi in
      Alaminos Canyon. Comparative 16S rRNA sequence analysis confirmed a single
      methanotroph-related symbiont in 'B.' childressi and a dual symbiosis with a
      methanotroph- and thiotroph-related symbiont in B. brooksi. A previously unknown
      diversity of four co-occurring symbionts was discovered in B. heckerae: a
      methanotroph, two phylogenetically distinct thiotrophs and a methylotroph-related
      phylotype not previously described from any marine invertebrate symbiosis. A gene
      characteristic of methane-oxidzing bacteria, pmoA, was identified in all three
      mussel species confirming the methanotrophic potential of their symbionts. Stable
      isotope analyses of lipids and whole tissue also confirmed the importance of
      methanotrophy in the carbon nutrition of all of the mussels. Analyses of absolute
      and relative symbiont abundance in B. heckerae and B. brooksi using fluorescence
      in situ hybridization (FISH) and rRNA slot blot hybridization indicated a clear
      dominance of methanotrophic over thiotrophic symbionts in their gill tissues. A
      site-dependent variability in total symbiont abundance was observed in B.
      brooksi, with specimens from Alaminos Canyon harbouring much lower densities than
      those from Atwater Valley. This shows that symbiont abundance is not species
      specific but can vary considerably between populations.

PMID- 17504481
TI  - Functionally distinct communities of ammonia-oxidizing bacteria along an
      estuarine salinity gradient.
AB  - The relationship between ammonia-oxidizing bacteria (AOB) and potential
      nitrification rates was examined along a salinity gradient in a New England
      estuary in spring and late summer over 3 years. Ammonia-oxidizing bacteria
      abundance was estimated by measuring gene copies of the ammonia monooxygenase
      catalytic subunit (amoA) using real-time polymerase chain reaction. Ammonia
      oxidizing bacteria abundance ranged from below detection to 6.0 x 10(7)amoA
      copies (gdw sediment)(-1). Mean potential nitrification rates ranged from 0.5 to
      186.5 nmol N (gdw sediment)(-1) day(-1). Both AOB abundance and potential rates
      were significantly higher in spring than late summer. Correlations between rates
      and abundance varied significantly among sites, but showed site-specific ammonia
      oxidation kinetics related to AOB community structure. The effect of salinity on
      potential nitrification rates was evaluated by incubating sediment from each site
      under four salinity conditions (0, 5, 10 and 30 psu). At all sites, rates were
      generally highest in the intermediate salinity treatments, but rates at the
      upstream site were inhibited at high salinity, while rates at the two downstream
      sites were inhibited at the lowest salinity. Although salinity appears to be an
      important factor in determining AOB distribution, it may not be the primary
      factor as AOB exhibited a broad range of salinity tolerance in our experiments.
      Our results indicate that there are significant differences in abundance and
      community composition of AOB along the salinity gradient, and the differences are
      reflected in community function.

PMID- 17504482
TI  - Effects of periodic desiccation on the synthesis of the UV-screening compound,
      scytonemin, in cyanobacteria.
AB  - Scytonemin is an ultraviolet radiation (UVR)-screening compound synthesized by
      some sheathed cyanobacteria exposed to high solar and sky radiation. It is
      primarily produced in response to UVA radiation, but certain environmental
      stresses can enhance synthesis. This study focuses on the effects of periodic
      desiccation on scytonemin synthesis in three desiccation-tolerant cyanobacterial
      strains, Nostoc punctiforme PCC 73102, Chroococcidiopsis CCMEE 5056 and
      Chroococcidiopsis CCMEE 246. Nostoc punctiforme and Chroococcidiopsis CCMEE 5056
      exposed to UVA radiation produced more concentrated scytonemin screens when
      experiencing periodic desiccation (i.e. 1 day desiccated for every 2 days
      hydrated) than when continuously hydrated. A more concentrated scytonemin screen
      would reduce the amount of UVR damage accrued when cells are desiccated and
      metabolically inactive. This might allow the cyanobacteria to allocate more
      energy to systems other than UVR damage repair during rehydration, which would
      facilitate recovery. The scytonemin screen is extremely stable, remaining largely
      intact in the sheaths of desiccated N. punctiforme even when continuously exposed
      to UVA radiation for about 2 months. In contrast to the above findings,
      scytonemin synthesis in Chroococcidiopsis CCMEE 246, a strain that produces
      scytonemin constitutively under low visible light (no UVA), was partially
      inhibited by periodic desiccation.

PMID- 17504483
TI  - Polyphyletic photosynthetic reaction centre genes in oligotrophic marine
      Gammaproteobacteria.
AB  - Ecological studies indicate that aerobic anoxygenic phototrophic bacteria (AAP)
      that use bacteriochlorophyll to support phototrophic electron transport are
      widely distributed in the oceans. All cultivated marine AAP are alpha-3 and alpha
      4 Proteobacteria, but metagenomic evidence indicates that uncultured AAP
      Gammaproteobacteria are important members of ocean surface microbial communities.
      Here we report the description of obligately oligotrophic, marine
      Gammaproteobacteria that have genes for aerobic anoxygenic photosynthesis. Three
      strains belonging to the OM60 clade were isolated in autoclaved seawater media.
      Polymerase chain reaction assays for the pufM gene show that these strains
      contain photosynthetic reaction centre genes. DNA sequencing and phylogenetic
      analysis indicate that the pufM genes are polyphyletic, suggesting multiple
      instances of lateral gene transfer. Peptide sequences from six photosynthesis
      genes (pufL, pufM, pufC, pufB, pufA and puhA) were detected by proteomic analyses
      of strain HTCC2080 cells grown aerobically in seawater. They closely match
      predicted peptides from an environmental seawater bacterial artificial chromosome
      clone of gammaproteobacterial origin, thus identifying the OM60 clade as a
      significant source of gammaproteobacterial AAP genes in marine systems. The cell
      yield and rate of growth of HTCC2080 in autoclaved, aerobic seawater increased in
      the light. These findings identify the OM60 clade as a source of
      Gammaproteobacteria AAP genes in coastal oceans, and demonstrate that aerobic,
      anoxygenic photosynthetic metabolism can enhance the productivity of marine
      oligotrophic bacteria that also grow heterotrophically in darkness.

PMID- 17504484
TI  - Assessing diversity and biogeography of aerobic anoxygenic phototrophic bacteria
      in surface waters of the Atlantic and Pacific Oceans using the Global Ocean
      Sampling expedition metagenomes.
AB  - Aerobic anoxygenic photosynthetic bacteria (AAnP) were recently proposed to be
      significant contributors to global oceanic carbon and energy cycles. However,
      AAnP abundance, spatial distribution, diversity and potential ecological
      importance remain poorly understood. Here we present metagenomic data from the
      Global Ocean Sampling expedition indicating that AAnP diversity and abundance
      vary in different oceanic regions. Furthermore, we show for the first time that
      the composition of AAnP assemblages change between different oceanic regions,
      with specific bacterial assemblages adapted to open ocean or coastal areas
      respectively. Our results support the notion that marine AAnP populations are
      complex and dynamic, and compose an important fraction of bacterioplankton
      assemblages in certain oceanic areas.

PMID- 17504485
TI  - Anaerobic ammonium-oxidizing bacteria in marine environments: widespread
      occurrence but low diversity.
AB  - Laboratory and field studies have indicated that anaerobic ammonium oxidation
      (anammox) is an important process in the marine nitrogen cycle. In this study 11
      additional anoxic marine sediment and water column samples were studied to
      substantiate this claim. In a combined approach using the molecular methods,
      polymerase chain reaction (PCR), qualitative and quantitative fluorescence in
      situ hybridization (FISH), as well as (15)N stable isotope activity measurements,
      it was shown that anammox bacteria were present and active in all samples
      investigated. The anammox activity measured in the sediment samples ranged from
      0.08 fmol cell(-1) day(-1) N(2) in the Golfo Dulce (Pacific Ocean, Costa Rica)
      sediment to 0.98 fmol cell(-1) day(-1) N(2) in the Gullmarsfjorden (North Sea,
      Sweden) sediment. The percentage of anammox cell of the total population (stained
      with DAPI) as assessed by quantitative FISH was highest in the Barents Sea (9% +/
      4%) and in most of the samples well over 2%. Fluorescence in situ hybridization
      and phylogenetic analysis of the PCR products derived from the marine samples
      indicated the exclusive presence of members of the Candidatus'Scalindua' genus.
      This study showed the ubiquitous presence of anammox bacteria in anoxic marine
      ecosystems, supporting previous observations on the importance of anammox for N
      cycling in marine environments.

PMID- 17504486
TI  - Ecophysiology of Defluviicoccus-related tetrad-forming organisms in an anaerobic
      aerobic activated sludge process.
AB  - A group of uncultured tetrad-forming organisms (TFOs) was enriched in an acetate
      fed anaerobic-aerobic sequencing membrane bioreactor showing deteriorated
      enhanced biological phosphorus removal capacity. Based on 16S rRNA gene clone
      library and fluorescence in situ hybridization (FISH) analyses, these TFOs were
      identified as novel members of the Defluviicoccus cluster in the
      Alphaproteobacteria, accounting for 90 +/- 5% of the EUBmix FISH-detectable
      bacterial cell area in the reactor biomass. Microautoradiography in combination
      with FISH and polyhydroxyalkanoate (PHA) staining revealed that these
      Defluviicoccus-related TFOs could take up and transform acetate, lactate,
      propionate and pyruvate, but not aspartic acid and glucose, into PHA under
      anaerobic conditions. In contrast, under continuous anaerobic-aerobic
      cultivation, Defluviicoccus vanus, the only cultured strain from the cluster, was
      able to take up glucose with concurrent glycogen consumption and PHA production
      under anaerobic conditions. Under subsequent aerobic conditions, the accumulated
      PHA was utilized and the biomass glycogen levels were restored. These findings
      not only re-confirmed these Defluviicoccus-related TFOs as glycogen-accumulating
      organisms, but also revealed unexpected levels of physiological, phylogenetic and
      morphological diversity among members of the Defluviicoccus cluster.

PMID- 17504487
TI  - Physiological, numerical and molecular characterization of alkyl ether-utilizing
      rhodococci.
AB  - Twenty-seven Gram-positive strains were characterized physiologically and
      numerically and classified them into four groups according to their specific
      activities for utilization of linear alkyl ethers (AEs), cyclic AEs,
      monoalkoxybenzenes and 1,4-diethoxybenzene. The comparative analysis of the 16S
      ribosomal RNA gene and 16S-23S intergenic spacer region showed that they belonged
      to the genera Rhodococcus and Gordonia. Alkyl ether-utilizing rhodococci appeared
      to involve various and diverse cytochromes P450 of the families CYP116 (25
      positive strains from 27), CYP153 (5/27), CYP249 (1/27) and a new family P450RR1
      (27/27). The presence of P450RR1 was strongly related to the specific activity
      for utilization of 2-methoxyphenol and 2-ethoxyphenol. In addition, 26 of 27
      strains contained multiple alkB genes coding for probable non-haem iron
      containing alkane monooxygenases and hydroxylases. Similar DNA fragments coding
      for a tetrahydrofuran monooxygenase A subunit (ThmA) were found in all cyclic AE
      utilizing strains and nearly identical DNA fragments coding for likely
      orthologues of a propane monooxygenase A subunit (PrmA) in all linear AE
      utilizing strains. The substrate availability in the degradation of aryl AEs,
      cyclic AEs and linear AEs agreed with the molecular probing of the respective
      genes encoding cytochrome P450RR1, ThmA and PrmA.

PMID- 17504488
TI  - Growth promotion of quorum-quenching bacteria in the rhizosphere of Solanum
      tuberosum.
AB  - Among 17 molecules structurally related to N-acylhomoserine lactone (NAHL), gamma
      caprolactone (GCL), 6-caprolactone (6CL) and 4-heptanolide (HTN) were found to
      stimulate the degradation of NAHL by bacterial communities recovered from bulk
      and rhizospheric soils. In the 6CL-, GCL- and HTN-treated bacterial consortia,
      the NAHL-degrading bacteria were more abundant than in control (mannitol-treated)
      consortia. Moreover, the GCL- and HTN-consortia showed a biocontrol activity
      against Pectobacterium atrosepticum in soft rot assays with tubers of Solanum
      tuberosum. When GCL was applied to hydroponic cultures of S. tuberosum, a
      significant increase of the ratio of NAHL-degrading bacteria among total
      cultivable bacteria was observed in several independent experiments. Most of
      these bacteria, the growth of which was stimulated by GCL amendment, were also
      able to use GCL as a sole carbon source. They belong to the Rhodococcus and
      Delftia genera. DGGE analysis revealed that GCL treatments affected the structure
      of bacterial communities. This work highlights the possibility to manage the NAHL
      degrading bacteria in a complex environment such as rhizosphere.

PMID- 17504490
TI  - Escherichia coli has multiple enzymes that attack TNT and release nitrogen for
      growth.
AB  - There has been a growing interest in the degradation of 2,4,6-trinitrotoluene
      (TNT) over the last decade, ever since its removal from polluted sites was
      declared an international environmental priority. Certain aerobic and anaerobic
      microorganisms are capable of using TNT as an N source, although very few studies
      have proven the mineralization of this compound. An unexpected observation in our
      laboratory led us to discover that certain Escherichia coli bench laboratory
      strains have multiple enzymes that attack TNT. One of the NemA products is
      responsible for the release of nitrite from the nitroaromatic ring: among the
      metabolites observed in vitro include Meisenheimer dihydride complexes of TNT
      from which 2-hydroxylamino-6-nitrotoluene is slowly formed during their
      rearomatization under concomitant release of nitrite. Furthermore, NemA, together
      with NfsA and NfsB reduce the nitro groups on the aromatic ring to the
      corresponding hydroxylamino derivatives, which probably results in the release of
      ammonium ions which can, in turn be used as a nitrogen source by E. coli for
      growth.

PMID- 17504489
TI  - In situ detection of novel Acidobacteria in microbial mats from a
      chemolithoautotrophically based cave ecosystem (Lower Kane Cave, WY, USA).
AB  - Lower Kane Cave, Wyoming (USA), has hydrogen sulfide-bearing springs that
      discharge into the cave passage. The springs and cave stream harbour white
      filamentous microbial mats dominated by Epsilonproteobacteria. Recently, novel
      16S rRNA gene sequences from the phylum Acidobacteria, subgroup 7, were found in
      these cave mats. Although Acidobacteria are ubiquitously distributed in many
      terrestrial and marine habitats, little is known about their ecophysiology. To
      investigate this group in Lower Kane Cave in more detail, a full-cycle rRNA
      approach was applied based on 16S and 23S rRNA gene clone libraries and the
      application of novel probes for fluorescence in situ hybridization. The 16S and
      23S rRNA gene clone libraries yielded seven and six novel acidobacterial
      operational taxonomic units (OTUs) respectively. The majority of the OTUs were
      affiliated with subgroups 7 and 8. One OTU was affiliated with subgroup 6, and
      one OTU could not be assigned to any of the present acidobacterial subgroups.
      Fluorescence in situ hybridization distinguished two morphologically distinct,
      rod-shaped cells of the acidobacterial subgroups 7 and 8. Although the
      ecophysiology of Acidobacteria from Lower Kane Cave will not be fully resolved
      until cultures are obtained, acidobacterial cells were always associated with the
      potentially chemolithoautotrophic epsilon- or gammaproteobacterial filaments,
      suggesting perhaps a lifestyle based on heterotrophy or chemoorganotrophy.

PMID- 17504491
TI  - The cyanotrophic bacterium Pseudomonas pseudoalcaligenes CECT5344 responds to
      cyanide by defence mechanisms against iron deprivation, oxidative damage and
      nitrogen stress.
AB  - Two-dimensional (2-D) electrophoresis approach has been used to test protein
      expression changes in response to cyanide in the alkaliphilic bacterium
      Pseudomonas pseudoalcaligenes CECT5344. This is a cyanide-assimilating strain
      which also grows in media containing cyanide-enriched effluent from the jewellery
      industry. The bacterium efficiently uses this residue as the sole nitrogen source
      for aerobic growth under alkaline pH with negligible nitrogen losses as HCN. Cell
      free extracts isolated from P. pseudoalcaligenes grown with a jewellery residue,
      free cyanide or ammonium chloride as nitrogen source were subjected to 2-D
      electrophoresis and the spot patterns were examined to determine differential
      protein expression. Electrophoretic plates exhibiting an average of 1000 spots
      showed significant differences in the expression of about 44 proteins depending
      on the nitrogen source. Some of these protein spots were analysed by Matrix
      assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF
      MS). Characterization of five of these proteins reveals that cyanide shock
      induces proteins related to iron acquisition, regulation of nitrogen assimilation
      pathways and oxidative stress repairing and protection.

PMID- 17504492
TI  - The ttgGHI solvent efflux pump operon of Pseudomonas putida DOT-T1E is located on
      a large self-transmissible plasmid.
AB  - Pseudomonas putida DOT-T1E is a solvent-tolerant strain able to grow in the
      presence of > 1% (v/v) toluene in the culture medium. A set of multidrug efflux
      pumps have been found to play a major role in the tolerance of this bacterium to
      organic solvents (Rojas et al., J Bacteriol 183: 3967-3973). In the course of
      studies of the mechanisms underlying solvent tolerance in DOT-T1E, we isolated a
      spontaneous solvent-sensitive mutant derivative which had lost the genes encoding
      the TtgGHI efflux pump, the most important extrusion element in quantitative
      terms. Genomic comparisons between the mutant and its parental strain by
      microarray analysis revealed that in addition to the ttgVW-ttgGHI gene cluster,
      another group of genes, highly similar to those found in the Tn4653A and ISPpu12
      transposable elements of the TOL plasmid pWW0 from P. putida mt-2, were also
      absent from this strain. Further analysis demonstrated that strain DOT-T1E
      harboured a large plasmid (named pGRT1) that was lost from the solvent-sensitive
      mutant. Mapping analysis revealed that the ttgVW-ttgGHI genes and the Tn4653A
      like transposon are borne by the pGRT1 plasmid. Plasmid pGRT1 is highly stable
      and its frequency of loss is below 10(-8) per cell per generation under a variety
      of growth conditions, including nutritional and physical stresses. The pGRT1
      plasmid is self-transmissible, and its acquisition by the toluene-sensitive P.
      putida KT2440 and Pseudomonas aeruginosa PAO1 increased the recipient's tolerance
      to toluene up to levels similar to those exhibited by P. putida DOT-T1E. We
      discuss the importance and potential benefits of this plasmid for the development
      of bacteria with enhanced solvent tolerance, and its potential impact for
      bioremediation and whole-cell biotransformations.

PMID- 17504493
TI  - Efficacy of intervention strategies for bioremediation of crude oil in marine
      systems and effects on indigenous hydrocarbonoclastic bacteria.
AB  - There is little information on how different strategies for the bioremediation of
      marine oil spills influence the key indigenous hydrocarbon-degrading bacteria
      (hydrocarbonoclastic bacteria, HCB), and hence their remediation efficacy.
      Therefore, we have used quantitative polymerase chain reaction to analyse changes
      in concentrations of HCB in response to intervention strategies applied to
      experimental microcosms. Biostimulation with nutrients (N and P) produced no
      measurable increase in either biodegradation or concentration of HCB within the
      first 5 days, but after 15 days there was a significant increase (29%; P < 0.05)
      in degradation of n-alkanes, and an increase of one order of magnitude in
      concentration of Thalassolituus (to 10(7) cells ml(-1)). Rhamnolipid
      bioemulsifier additions alone had little effect on biodegradation, but, in
      combination with nutrient additions, provoked a significant increase: 59% (P <
      0.05) more n-alkane degradation by 5 days than was achieved with nutrient
      additions alone. The very low Alcanivorax cell concentrations in the microcosms
      were hardly influenced by addition of nutrients or bioemulsifier, but strongly
      increased after their combined addition, reflecting the synergistic action of the
      two types of biostimulatory agents. Bioaugmentation with Thalassolituus
      positively influenced hydrocarbon degradation only during the initial 5 days and
      only of the n-alkane fraction. Bioaugmentation with Alcanivorax was clearly much
      more effective, resulting in 73% greater degradation of n-alkanes, 59% of
      branched alkanes, and 28% of polynuclear aromatic hydrocarbons, in the first 5
      days than that obtained through nutrient addition alone (P < 0.01). Enhanced
      degradation due to augmentation with Alcanivorax continued throughout the 30-day
      period of the experiment. In addition to providing insight into the factors
      limiting oil biodegradation over time, and the competition and synergism between
      HCB, these results add weight to the use of bioaugmentation in oil pollution
      mitigation strategies.

PMID- 17504494
TI  - A novel Dps-type protein from insect gut bacteria catalyses hydrolysis and
      synthesis of N-acyl amino acids.
AB  - A novel type of a microbial N-acyl amino acid hydrolase (AAH) from insect gut
      bacteria was purified, cloned and functionally characterized. The enzyme was
      obtained from Microbacterium arborescens SE14 isolated from the foregut of larvae
      of the generalist herbivore Spodoptera exigua. The substrates of AAH are N-acyl
      glutamines previously reported to elicit plant defence reactions after
      introduction into the leaf during feeding. The isolated AAH catalyses the
      hydrolysis of the amide bond (K(m) = 36 micromol l(-1)) and, less efficient, the
      formation (K(m) = 3 mmol l(-1)) of the elicitor active N-acyl amino acids. The
      AAH from M. arborescens SE14 shows no homology to known fatty acyl amidases (EC
      3.5.1.4) but belongs to the family of Dps proteins (DNA-binding protein from
      starved cell). In line with other DPS proteins AAH is a homododecamer (monomer 17
      181 Da) and contains iron atoms (c. 1-16 iron atoms per subunit). Unlike genuine
      DPS proteins the enzyme does not significantly bind DNA. Amino acid hydrolase is
      the first member of the DPS family that catalyses the cleavage or formation of
      amide bonds. The participation of a microbial enzyme in the homeostasis of N-acyl
      glutamines in the insect gut adds further complexity to the interaction between
      plants and their herbivores.

PMID- 17504495
TI  - Community dynamics and heterogeneities in mixed bacterial communities subjected
      to nutrient periodicities.
AB  - Sixteen replicate microcosms were inoculated with a mixed assemblage of
      heterotrophic bacteria and provided with discrete pulses of protein as carbon and
      energy source. The dynamics of community structure were monitored by 16S rRNA
      gene polymerase chain reaction denaturant gradient gel electrophoresis (PCR
      DGGE). The results were consistent with a strong role for biological interactions
      in maintaining diversity. Replicate microcosms developed different microbial
      communities. For systems exposed to nutrient pulses every 7 days, the number of
      DGGE bands averaged 13 +/- 4 (mean +/- SD) and the Dice similarity coefficient
      between pairs ranged from 0.08 to 0.67. In each of 16 systems provided protein
      once each day, there were dynamic changes over the first 30 days but community
      composition was stable over the next 20 days. However, most systems differed from
      each other; two-thirds of the pairwise comparisons had similarity coefficients in
      the range of 0.35-0.63. These 16 systems contained 10 +/- 2 phylotypes (mean +/-
      SD) and in aggregate 34 phylotypes were found in the 16 systems. Most phylotypes
      were found in < 25% of the systems, and there were not strong networks of
      association among phylotypes.

PMID- 17504496
TI  - Nitrogenase gene expression in the Chesapeake Bay Estuary.
AB  - Like many estuaries, the Chesapeake Bay has pronounced gradients in salinity and
      nutrients. Previous studies have shown that there is a high diversity of
      nitrogenase (nifH) genes in the estuary, and that there are specific
      distributions of individual nifH phylotypes. In contrast to previous work that
      revealed the remarkable diversity of nifH phylotypes in the Chesapeake estuary,
      in this study of nifH expression we only detected two phylotypes, and both were
      phylogenetically related to cyanobacterial nifH genes. One of the phylotypes was
      closely related to a nifH sequence from the filamentous, heterocystous
      cyanobacterium Anabaena cylindrica, and was found at the head of the estuary. The
      other phylotype was found in a sample collected near the mouth of the estuary and
      was closely related to nifH sequences from Group A unicellular cyanobacteria,
      which has previously been reported in oceanic waters only. These nifH phylotypes
      had distinct patterns of expression that were restricted to different regions of
      the Chesapeake Bay. This study provides the first evidence of nifH expression in
      the Chesapeake Bay, and suggests that diazotrophic unicellular cyanobacteria have
      a broader distribution and activity than previously recognized.

PMID- 17504497
TI  - Collimonas fungivorans, an unpredicted in vitro but efficient in vivo biocontrol
      agent for the suppression of tomato foot and root rot.
AB  - Although bacteria from the genus Collimonas have demonstrated in vitro antifungal
      activity against many different fungi, they appeared inactive against the plant
      pathogenic fungus Fusarium oxysporum f.sp. radicis-lycopersici (Forl), the causal
      agent of tomato foot and root rot (TFRR). Visualization studies using
      fluorescently labelled organisms showed that bacterial cells attached extensively
      to the fungal hyphae under nutrient-poor conditions but not in glucose-rich
      Armstrong medium. Collimonas fungivorans was shown to be as efficient in
      colonizing tomato root tips as the excellent colonizer Pseudomonas fluorescens
      strain WCS365. Furthermore, it appeared to colonize the same sites on the root as
      did the phytopathogenic fungus. Under greenhouse conditions in potting soil, C.
      fungivorans performed as well in biocontrol of TFRR as the well-established
      biocontrol strains P. fluorescens WCS365 and Pseudomonas chlororaphis PCL1391.
      Moreover, under biocontrol conditions, C. fungivorans did not attach to Forl
      hyphae colonizing plant roots. Based on these observations, we hypothesize that
      C. fungivorans mainly controls TFRR through a mechanism of competition for
      nutrients and niches rather than through its reported mycophagous properties, for
      which attachment of the bacteria to the fungal hyphae is assumed to be important.

PMID- 17504498
TI  - An Acanthamoeba sp. containing two phylogenetically different bacterial
      endosymbionts.
AB  - Acanthamoebae are ubiquitous free-living amoebae and important predators of
      microbial communities. They frequently contain obligate intracellular bacterial
      symbionts, which show a worldwide distribution. All Acanthamoeba spp. described
      so far harboured no or only a single specific endosymbiont phylotype, and in some
      cases evidence for coevolution between the symbiotic bacteria and the amoeba host
      has been reported. In this study we have isolated and characterized an
      Acanthamoeba sp. (strain OEW1) showing a stable symbiotic relationship with two
      morphologically different endosymbionts. 16S rRNA sequence analysis assigned
      these symbionts to the candidate genus Procabacter (Betaproteobacteria) and the
      genus Parachlamydia (Chlamydiae) respectively. Fluorescence in situ hybridization
      and transmission electron microscopy confirmed the affiliation of the
      endosymbionts and showed their co-occurrence in the amoeba host cells and their
      intracellular location within separate compartments enclosed by host-derived
      membranes. Further analysis of this stable relationship should provide novel
      insights into the complex interactions of intracellular multiple-partner
      associations.

PMID- 17504499
TI  - Cave microbiology.

PMID- 17504500
TI  - Opportunism of Conidiobolus obscurus stems from depression of infection in situ
      to progeny colonies of host alatae as disseminators of the aphid-pathogenic
      fungus.

PMID- 17504501
TI  - Mapping susceptibility gene locus for IgA deficiency at del(18)(q22.3-q23);
      report of familial cryptic chromosome t(18q; 10p) translocations.
AB  - This study presents a clinical report of the Finnish chromosome t(18q; 10p)
      translocation family with an overview of eight other selected immunoglobulin A
      (IgA)-deficient 18q deletion (18q-) patients from seven published articles. The
      family members show features common to 18q- syndrome such as mental retardation,
      multiple facial dysmorphism, foot/hand deformities, abnormal myelination of brain
      white matter, and a spectrum of immunological/infectious disorders including IgA
      deficiency (IgAD). Genotype-phenotype correlation study of the unbalanced t(18q-;
      10p+) translocation family members and other 18q- syndrome reports led to
      definition of a potential susceptibility gene locus for IgAD at distal region of
      18q22.3-q23 between markers D18S812-18qter. The haplo-insufficiency of the
      18q22.3-q23 gene region is suggested to be a cause of the IgAD phenotype in 18q-
      individuals. This 7 Mb IgAD critical region shows significant association with
      susceptibility region for celiac disease that is frequently connected to IgAD.

PMID- 17504502
TI  - Association between genetic polymorphisms in the human interleukin-7 receptor
      alpha-chain and inhalation allergy.
AB  - Thymic stromal-derived lymphopoietin (TSLP) and interleukin-7 share a common
      receptor chain, IL-7Ralpha. IL-7 is involved in T-cell homeostasis, and TSLP
      induces production of pro-allergic cytokines. The gene encoding the IL-7Ralpha
      chain is polymorphic, and investigation of inhalation allergic patients compared
      with controls showed significant association with two alleles at position +1237
      and +2087.

PMID- 17504503
TI  - Distribution of CCR2 polymorphism in HIV-1-infected and healthy subjects in North
      India.
AB  - Substitution of V64I in CCR2 relates to delayed progression to AIDS and protects
      against HIV-1 infection. We examined the distribution of V64I in HIV-infected and
      healthy North Indian subjects. No significant difference in the allele or
      genotype distribution of CCR2 V64I polymorphism was observed, indicating that
      there is no association between CCR2 V64I polymorphism and susceptibility to HIV
      infection in North Indian population.

PMID- 17504504
TI  - A diplotype in the lymphotoxin alpha gene is associated with differential
      expression of LTA mRNA induced by Gram-positive and Gram-negative bacteria.
AB  - We sequenced the lymphotoxin alpha (LTA) promoter and identified LTA10G>A in
      strong linkage with LTA252G>A and LTA723C>A. Stimulated cells from LTA723AA:
      LTA252GG:LTA10AA individuals had significantly higher LTA mRNA levels than
      LTA723CC:LTA252AA:LTA10GG and LTA723AA:LTA252AG:LTA10GA individuals, suggesting
      that this diplotype may contain a functional polymorphism explaining the observed
      disease associations with LTA252G>A.

PMID- 17504505
TI  - Polymorphism of ZuBeCa3 microsatellite and its association with mammary tumor in
      dogs.
AB  - A study was conducted to explore the genetic polymorphism at ZuBeCa3
      microsatellite and to estimate the association between microsatellite
      polymorphism and mammary cancer in dogs. Three genotypes namely AA, AB and BB
      were observed both in dogs affected by mammary cancer and in non-affected dogs.
      In the affected group, the frequency of genotype and allele was 0.63 for AA, 0.25
      for AB and 0.12 for BB genotype, and 0.76 for A and 0.24 for B allele. In the
      nonaffected group, the frequency of AA, AB and BB genotype was 0.39, 0.38 and
      0.23 and the frequency of A and B allele was 0.58 and 0.42, respectively.
      Histopathological observation classified the cancer-affected animals into three
      groups namely, malignant solid mammary carcinoma, malignant papillary
      adenocarcinoma and benign papillary adenoma in which the frequency of A allele
      was relatively more predominant in benign tumor group, which is more than 80%.
      Statistical tests showed significant differences (P < 0.01) of allelic
      distribution between tumor-affected and non-affected group, which reveals the
      effect of polymorphism on occurrences of mammary cancer in dogs. Besides, chi(2)
      test also reflected the significant effect of genotypes on occurrences of three
      groups of mammary cancer in dogs.

PMID- 17504506
TI  - Cloning and sequencing of ovine Flt3 ligand.
AB  - A cDNA (879 bp) containing the complete open reading frame of ovine Fms-related
      tyrosine kinase 3 ligand (Flt3-L) was amplified by reverse transcriptase
      polymerase chain reaction (RT-PCR), cloned and sequenced. The deduced amino acid
      sequence has 97.6% similarity with bovine Flt3-L isoform 1 and shares the long
      cytoplasmic domain observed in bovine Flt3-L but not in human Flt3-L.

PMID- 17504507
TI  - Cloning, sequencing and expression of cDNA of bovine neutrophil beta-defensin
      from water buffalo (Bubalus bubalis).
AB  - Neutrophil beta-defensins have been identified as naturally occurring potent
      antibacterial cationic peptides serving as effector molecules of innate immunity
      that provide a first line of defence against pathogens. Considering the broad
      spectrum antimicrobial activity against microorganisms and role in innate
      immunity of the neutrophil beta-defensins, it has been characterized in many
      livestock species including cattle, sheep, caprine and porcines. Here we report
      the isolation, cloning, sequencing and expression of precursor bovine neutrophil
      beta-defensin isolated from Indian water buffalo. Full-length cDNA was amplified
      using reverse transcription polymerase chain reaction (RT-PCR). The cDNA
      contained an open reading frame of 192 bp encoding a putative polypeptide of 63
      amino acids. Deduced amino acid sequence of buffalo BNBD4 showed varying amino
      acid identity with the published sequences of related beta-defensins of other
      domestic ruminant species ranging from 67.18 to 79.68%. Recombinant buffalo
      defensin was produced in Escherichia coli as fusion protein.

PMID- 17504508
TI  - CARD15 variants determine a disturbed early response of monocytes to adherent
      invasive Escherichia coli strain LF82 in Crohn's disease.
AB  - Caspase activation and recruitment domain 15 (CARD15) and Toll-like receptor 4
      (TLR4) are respectively intracellular and membrane-bound receptors for bacterial
      cell wall components [respectively muramyl dipeptide (MDP) and lipopolysaccharide
      (LPS)]. Polymorphisms in CARD15 and TLR4 have been linked with Crohn's disease
      (CD). Adherent-invasive Escherichia coli (AIEC) strains with particular adhesion
      and invasion characteristics have been specifically associated with CD ileal
      mucosa. The aim of this study was to investigate the functional impact of these
      polymorphisms on monocytes in patients with CD, in response to MDP, LPS and AIEC
      strain LF82. Monocytes were isolated from 40 patients with CD using magnetic cell
      sorting, stimulated with LPS or MDP or infected with AIEC. IL-1beta, IL-6, IL-8,
      IL-10, IL-12 and tumour necrosis factor alpha induction was assessed using
      quantitative real time-polymerase chain reaction, Cytometric Bead Array and
      ELISA. Bacterial intracellular survival and replication was assessed using a
      gentamicin protection assay. Results were linked with the presence of CARD15 and
      TLR4 polymorphisms. Monocytes of patients with CARD15 polymorphisms showed an
      early reduced cytokine response (IL-1beta, IL-6 and IL-10) to infection with
      AIEC, which was restored after 20 h. A gene-dose effect was seen, comparing wild
      types, heterozygotes and homozygotes. We found no differences in intracellular
      survival and replication of AIEC. Heterozygous carriage of TLR4 polymorphisms did
      not influence monocyte response. In conclusion, patients with CD carrying CARD15
      polymorphisms show a disturbed early inflammatory monocyte response after
      infection with AIEC strain LF82. For the first time, a functional defect was
      detected in single heterozygous carriers. These findings reflect the potential
      role of a genetically altered host response to disease-related bacteria in the
      pathogenesis of CD.

PMID- 17504509
TI  - Interleukin-12B-3'UTR polymorphism in association with IL-12p40 and IL-12p70
      serum levels and silicosis severity.
AB  - Susceptibility to silicosis and to disease severity is in part genetically
      determined. In this study, the role of IL-12B-3'UTR polymorphism in
      susceptibility and severity of silicosis and its influence on IL-12p40 and IL
      12p70 serum level were investigated. The quantity of IL-12p40 and IL-12p70 was
      detected by enzyme-linked immunosorbent assay and the genotype of IL-12B was
      determined using the polymerase chain reaction-restriction fragment-length
      polymorphism method. We observed elevated IL-12p40 in contrast to IL-12p70 serum
      levels in a group of 62 silicosis patients compared with both control groups. In
      severe silicosis patients, we detected the highest IL-12p40 serum levels (129.1
      +/- 67.7 pg mL(-1)); lower in patients with the moderate (94 +/- 41.6 pg mL(-1)),
      whereas in mild silicosis, the IL-12p40 levels (67 +/- 23.5 pg mL(-1)) was
      similar to these in healthy donors. According to IL-12B polymorphism, increased
      serum levels were observed in subjects with AA genotype (103.2 +/- 46.9 pg mL(
      1)) compared to silicosis patients with AC genotype (82.7 +/- 38.3 pg mL(-1)). No
      significant differences of genotype and allele frequencies of the 3'UTR
      polymorphism were observed between silicosis patients and healthy controls.
      However, the heterozygous genotype was found approximately five times more
      frequently in patients with mild and moderate (48% and 52%) silicosis compared to
      patients with severe silicosis (11%), and that IL-12B polymorphism may contribute
      to silicosis severity rather than to susceptibility. Our data demonstrated that
      elevated serum IL-12p40, independently of IL-12p70 levels, is associated with
      severity of silicosis, and suggested that IL-12p40 profibrotic activity may
      contribute to silicosis severity.

PMID- 17504510
TI  - Molecular diversity of HLA-A, -B and -C alleles in a North Indian population as
      determined by PCR-SSOP.
AB  - We have used molecular methods to determine the frequencies of human leukocyte
      antigen (HLA)-A, -B and -C alleles in normal, healthy, unrelated individuals from
      North India using polymerase chain reaction and hybridization with sequence
      specific oligonucleotide probes as there is no comprehensive report showing
      molecular diversity of all the class-I alleles present in North Indians. A*0101,
      A*0206, A*0301, A*1101, A*6801, A*2401 and A*3101 were the most prevalent alleles
      of the A locus with 91.11% of the samples showing heterozygosity. At the HLA-B
      locus a total of 47 B locus alleles were observed and the only allele found with
      an allele frequency of 15% was B*5801. Other frequent B-locus alleles observed
      were B*5101, B*3503 and B*4006 with relatively less frequent alleles like B*5201,
      B*3501, B*0702, B*4403, B*5701, B*1801 and B*5501. Of the samples studied 92.31%
      were heterozygous for B-locus alleles. Cw*0602 and Cw*0401 were the most frequent
      C-locus alleles. Other frequent C-locus alleles were Cw*0102, Cw*0302, Cw*0701,
      Cw*0702, Cw*1202, Cw*1203, Cw*1502 and Cw*1503. HLA alleles common in Africans
      like B*5801, A*68012, B*5301, B*44032, B*4006 and Cw*1701 were observed in the
      North Indians besides oriental alleles like B*1301, B*1502 and B*4001 confirming
      that the genetic make-up of North Indians is Caucasoid with elements of Mongoloid
      and Negrito races. Some new/rare alleles like B*1802, described as a new allele
      from Thailand and B*8101, described earlier in a Bubi population were also
      observed although with low frequencies, showing the diversity of HLA class-I
      alleles present in the North Indians.

PMID- 17504511
TI  - A polymorphism in FAS gene promoter correlated with circulating soluble FAS
      levels.
AB  - The -670FAS (A/G) polymorphism and elevated concentrations of the soluble form of
      FAS (sFAS) have been associated with neoplasic and autoimmune diseases. This
      polymorphism in the Fas promoter gene could modulate the transcription of Fas
      expression and therefore, contribute to these pathologies. The in vivo functional
      significance of the FAS polymorphism was investigated by assessing the
      correlation between FAS genotypes and the serum-circulating FAS (sFAS) levels. We
      determined the FAS polymorphism distributions by restriction fragment-length
      polymorphism-polymerase chain reaction in 170 normal subjects. We used enzyme
      linked immunosorbent assay to evaluate the sFAS levels in 44 of these
      individuals. Assessment of the concentration of sFAS indicated that the level of
      sFAS in subjects carrying the FAS-A/A genotype was significantly higher than that
      of those carrying the G/G genotype (3.90 ng mL(-1) vs. 3.12 ng mL(-1), P =
      0.035). Our results demonstrated that FAS promoter polymorphism was significantly
      associated with the level of soluble FAS production in normal subjects.

PMID- 17504512
TI  - No relationship observed between human p53 codon-72 genotype and HPV-associated
      cervical cancer in a population group with a low arginine-72 allele frequency.
AB  - Infection with high-risk human papillomavirus (HR-HPV) is a necessary but not a
      sufficient event in the development of cervical cancer, as most infections
      regress without intervention. Thus, genetic host factors and cellular immune
      responses could be potential modifiers for the risk of developing cervical
      cancer. In particular, p53 is considered as the most critical tumour suppressor
      gene and is involved in regulating cell division. The polymorphism on p53, which
      encodes either a proline or an arginine amino acid residue at codon 72, has been
      reported as a possible risk factor for cervical disease. This polymorphism has
      been shown to differentially affect the efficiency of degradation of p53 protein
      mediated by HR-HPV E6 oncoprotein. Women with histologically proven cancer of the
      cervix (n = 111) and hospital-based controls (n = 143) were included in this
      study. The patients and controls were from the Western Cape Province in South
      Africa. Genotyping of the p53 polymorphism was conducted using polymerase chain
      reaction and restriction fragment-length polymorphism method. The distributions
      of the allelic frequencies were stratified in both patients and controls into two
      South African ethnic population groups. In this study, we observed no association
      between the distribution of p53 polymorphism and susceptibility to cervical
      cancer in the Western Cape Province populations (P = 0.466). However, the
      frequency of the Pro/Pro residue at codon 72 was increased in the South African
      population when compared to Caucasians, Indians and Portuguese population groups.
      Notably, as the distribution of the Pro/Pro at codon 72 of p53 gene was
      significantly different (P < 0.05) between the control groups of South Africa and
      other population groups. This result suggests that ethnic disparity may influence
      the levels of p53 produced.

PMID- 17504515
TI  - Retraction.

PMID- 17504516
TI  - Unexpected observations after mapping LongSAGE tags to the human genome.
AB  - BACKGROUND: SAGE has been used widely to study the expression of known
      transcripts, but much less to annotate new transcribed regions. LongSAGE produces
      tags that are sufficiently long to be reliably mapped to a whole-genome sequence.
      Here we used this property to study the position of human LongSAGE tags obtained
      from all public libraries. We focused mainly on tags that do not map to known
      transcripts. RESULTS: Using a published error rate in SAGE libraries, we first
      removed the tags likely to result from sequencing errors. We then observed that
      an unexpectedly large number of the remaining tags still did not match the genome
      sequence. Some of these correspond to parts of human mRNAs, such as polyA tails,
      junctions between two exons and polymorphic regions of transcripts. Another non
      negligible proportion can be attributed to contamination by murine transcripts
      and to residual sequencing errors. After filtering out our data with these
      screens to ensure that our dataset is highly reliable, we studied the tags that
      map once to the genome. 31% of these tags correspond to unannotated transcripts.
      The others map to known transcribed regions, but many of them (nearly half) are
      located either in antisense or in new variants of these known transcripts.
      CONCLUSION: We performed a comprehensive study of all publicly available human
      LongSAGE tags, and carefully verified the reliability of these data. We found the
      potential origin of many tags that did not match the human genome sequence. The
      properties of the remaining tags imply that the level of sequencing error may
      have been under-estimated. The frequency of tags matching once the genome
      sequence but not in an annotated exon suggests that the human transcriptome is
      much more complex than shown by the current human genome annotations, with many
      new splicing variants and antisense transcripts. SAGE data is appropriate to map
      new transcripts to the genome, as demonstrated by the high rate of cross
      validation of the corresponding tags using other methods.

PMID- 17504517
TI  - TP53 mutation status and gene expression profiles are powerful prognostic markers
      of breast cancer.
AB  - INTRODUCTION: Gene expression profiling of breast carcinomas has increased our
      understanding of the heterogeneous biology of this disease and promises to impact
      clinical care. The aim of this study was to evaluate the prognostic value of gene
      expression-based classification along with established prognostic markers and
      mutation status of the TP53 gene (tumour protein p53) in a group of breast cancer
      patients with long-term (12 to 16 years) follow-up. METHODS: The clinical and
      histopathological parameters of 200 breast cancer patients were studied for their
      effects on clinical outcome using univariate/multivariate Cox regression. The
      prognostic impact of mutations in the TP53 gene, identified using temporal
      temperature gradient gel electrophoresis and sequencing, was also evaluated.
      Eighty of the samples were analyzed for gene expression using 42 K cDNA
      microarrays and the patients were assigned to five previously defined molecular
      expression groups. The strength of the gene expression based classification
      versus standard markers was evaluated by adding this variable to the Cox
      regression model used to analyze all samples. RESULTS: Both univariate and
      multivariate analysis showed that TP53 mutation status, tumor size and lymph node
      status were the strongest predictors of breast cancer survival for the whole
      group of patients. Analyses of the patients with gene expression data showed that
      TP53 mutation status, gene expression based classification, tumor size and lymph
      node status were significant predictors of survival. Breast cancer cases in the
      'basal-like' and 'ERBB2+' gene expression subgroups had a very high mortality the
      first two years, while the 'highly proliferating luminal' cases developed the
      disease more slowly, showing highest mortality after 5 to 8 years. The TP53
      mutation status showed strong association with the 'basal-like' and 'ERBB2+'
      subgroups, and tumors with mutation had a characteristic gene expression pattern.
      CONCLUSION: TP53 mutation status and gene-expression based groups are important
      survival markers of breast cancer, and these molecular markers may provide
      prognostic information that complements clinical variables. The study adds
      experience and knowledge to an ongoing characterization and classification of the
      disease.

PMID- 17504520
TI  - Investigating the effects of external fields polarization on the coupling of pure
      magnetic waves in the human body in very low frequencies.
AB  - In this paper we studied the effects of external fields' polarization on the
      coupling of pure magnetic fields into human body. Finite Difference Time Domain
      (FDTD) method is used to calculate the current densities induced in a 1 cm
      resolution anatomically based model with proper tissue conductivities. Twenty
      different tissues have been considered in this investigation and scaled FDTD
      technique is used to convert the results of computer code run in 15 MHz to low
      frequencies which are encountered in the vicinity of industrial induction heating
      and melting devices. It has been found that external magnetic field's orientation
      due to human body has a pronounced impact on the level of induced currents in
      different body tissues. This may potentially help developing protecting
      strategies to mitigate the situations in which workers are exposed to high levels
      of external magnetic radiation.

PMID- 17504519
TI  - Antisense oligonucleotide inhibition of heat shock protein (HSP) 47 improves
      bleomycin-induced pulmonary fibrosis in rats.
AB  - BACKGROUND: The most common pathologic form of pulmonary fibrosis arises from
      excessive deposition of extracellular matrix proteins such as collagen. The 47
      kDa heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that
      has been shown to play a major role during the processing and/or secretion of
      procollagen. OBJECTIVES: To determine whether inhibition of HSP47 could have
      beneficial effects in mitigating bleomycin-induced pulmonary fibrosis in rats.
      METHODS: All experiments were performed with 250-300 g male Wistar rats. Animals
      were randomly divided into five experimental groups that were administered: 1)
      saline alone, 2) bleomycin alone, 3) antisense HSP47 oligonucleotides alone, 4)
      bleomycin + antisense HSP47 oligonucleotides, and 5) bleomycin + sense control
      oligonucleotides. We investigated lung histopathology and performed immunoblot
      and immunohistochemistry analyses. RESULTS: In rats treated with HSP47 antisense
      oligonucleotides, pulmonary fibrosis was significantly reduced. In addition,
      treatment with HSP47 antisense oligonucleotides significantly improved bleomycin
      induced morphological changes. Treatment with HSP47 antisense oligonucleotides
      alone did not produce any significant changes to lung morphology. Immunoblot
      analyses of lung homogenates confirmed the inhibition of HSP47 protein by
      antisense oligonucleotides. The bleo + sense group, however, did not exhibit any
      improvement in lung pathology compared to bleomycin alone groups, and also had no
      effect on HSP47 expression. CONCLUSION: These findings suggest that HSP47
      antisense oligonucleotide inhibition of HSP47 improves bleomycin-induced
      pulmonary fibrosis pathology in rats.

PMID- 17504518
TI  - Central core disease.
AB  - Central core disease (CCD) is an inherited neuromuscular disorder characterised
      by central cores on muscle biopsy and clinical features of a congenital myopathy.
      Prevalence is unknown but the condition is probably more common than other
      congenital myopathies. CCD typically presents in infancy with hypotonia and motor
      developmental delay and is characterized by predominantly proximal weakness
      pronounced in the hip girdle; orthopaedic complications are common and malignant
      hyperthermia susceptibility (MHS) is a frequent complication. CCD and MHS are
      allelic conditions both due to (predominantly dominant) mutations in the skeletal
      muscle ryanodine receptor (RYR1) gene, encoding the principal skeletal muscle
      sarcoplasmic reticulum calcium release channel (RyR1). Altered excitability
      and/or changes in calcium homeostasis within muscle cells due to mutation-induced
      conformational changes of the RyR protein are considered the main pathogenetic
      mechanism(s). The diagnosis of CCD is based on the presence of suggestive
      clinical features and central cores on muscle biopsy; muscle MRI may show a
      characteristic pattern of selective muscle involvement and aid the diagnosis in
      cases with equivocal histopathological findings. Mutational analysis of the RYR1
      gene may provide genetic confirmation of the diagnosis. Management is mainly
      supportive and has to anticipate susceptibility to potentially life-threatening
      reactions to general anaesthesia. Further evaluation of the underlying molecular
      mechanisms may provide the basis for future rational pharmacological treatment.
      In the majority of patients, weakness is static or only slowly progressive, with
      a favourable long-term outcome.

PMID- 17504521
TI  - Analysis of a possible independent origin of triploid P. formosa outside of the
      Rio Purificacion river system.
AB  - BACKGROUND: Unisexuality, or all female reproduction, is rare among vertebrates.
      Studying these exceptional organisms may give useful information with respect to
      the evolution and maintenance of sexual reproduction. Poecilia formosa was the
      first unisexual vertebrate species to be detected and since then has served as a
      paradigmatic organism for unisexuality and studies on the evolution of sex. It
      reproduces through gynogenesis, using sperm of males from related species to
      trigger parthenogenetic development of the unreduced diploid eggs. Like in other
      unisexual vertebrates, triploids occur in a certain range of P. formosa. It has
      been suggested that the addition of the host species derived third chromosome set
      is evolutionary important. Clonal organisms lack sufficient genotypic diversity
      for adaptive changes to variable environments. Also non-recombining genomes
      cannot purge deleterious mutations and therefore unisexual organisms should
      suffer from a genomic decay. Thus, polyploidization leading to triploidy should
      bring "fresh" genetic material into the asexual lineage. To evaluate the
      importance of triploidy for maintaining the asexual species, it is important to
      know whether such an introgression event happens at a reasonable frequency.
      RESULTS: In an earlier study it was found that all triploid P. formosa in the Rio
      Purificacion river system are of monophyletic origin. Here we have analyzed fish
      from a different river system. Using microsatellite analysis we can show that the
      triploids from this new location are genetically divergent and most probably of
      an independent origin. CONCLUSION: Our data support the hypothesis that triploidy
      was not a single chance event in the evolutionary history of P. formosa and hence
      might be a relevant mechanism to increase genotypic divergence and at least
      partially counteract the genetic degeneration connected to asexuality. It is,
      however, much rarer than in other asexual vertebrates analyzed so far and thus
      probably only of moderate evolutionary importance for the maintenance of the
      asexual breeding complex.

PMID- 17504523
TI  - Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid
      particle-mediated cholesterol release from neurons.
AB  - BACKGROUND: Since the majority of apolipoprotein E (apoE) existing in the
      cerebrospinal fluid is associated with high-density lipoprotein (HDL), one should
      focus on the role of the apoE-HDL complex rather than on that of free apoE in
      cholesterol metabolism in the central nervous system. However, the apoE-isoform
      specific effect of apoE-HDL on cholesterol transport remains unclarified.
      RESULTS: Here we show that apoE3-HDL induced a marked cholesterol release from
      neurons, while apoE4-HDL induced little. To elucidate the mechanism underlying
      this phenomenon, we used a complex of lipid emulsion (EM) with recombinant apoE3
      or apoE4 (apoE-EM) at various apoE concentrations. When a small number of apoE
      molecules were associated with EM, apoE3- and apoE4-EM, induced a marked
      cholesterol release to a level similar to that induced by EM alone. However, when
      apoE at given concentrations was incubated with EM, apoE3-EM induced a marked
      cholesterol release, while apoE4-EM induced little. Under these conditions, a
      greater number of apoE4 molecules were associated with EM than apoE3 molecules.
      When an increasing number of apoE molecules were associated with EM, both apoE3
      EM and apoE4-EM induced little cholesterol release. Preincubation with beta
      mercaptoethanol increased the number of apoE3 molecules associated with EM
      similar to that of apoE4 molecules, indicating that the presence (apoE3) or
      absence (apoE4) of intermolecular disulfide bond formation is responsible for the
      association of a greater number of apoE4 molecules to EM than apoE3 molecules.
      CONCLUSION: These results suggest that although apoE and a lipid particle are
      lipid acceptors, when apoE and a lipid particle form a complex, apoE on the
      particle surface inhibits the lipid particle-mediated cholesterol release from
      cells in an apoE-concentration-dependent manner.

PMID- 17504522
TI  - Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on
      activated CD4+ and CD8+ T cells.
AB  - BACKGROUND: We previously identified the glucose transporter Glut-1, a member of
      the multimembrane-spanning facilitative nutrient transporter family, as a
      receptor for both HTLV-1 and HTLV-2. However, a recent report concluded that Glut
      1 cannot serve as a receptor for HTLV-1 on CD4 T cells: This was based mainly on
      their inability to detect Glut-1 on this lymphocyte subset using the commercial
      antibody mAb1418. It was therefore of significant interest to thoroughly assess
      Glut-1 expression on CD4 and CD8 T cells, and its association with HTLV-1 and -2
      envelope binding. RESULTS: As previously reported, ectopic expression of Glut-1
      but not Glut-3 resulted in significantly augmented binding of tagged proteins
      harboring the receptor binding domains of either HTLV-1 or HTLV-2 envelope
      glycoproteins (H1RBD or H2RBD). Using antibodies raised against the carboxy
      terminal peptide of Glut-1, we found that Glut-1 expression was significantly
      increased in both CD4 and CD8 cells following TCR stimulation. Corresponding
      increases in the binding of H1RBD as well as H2RBD, not detected on quiescent T
      cells, were observed following TCR engagement. Furthermore, increased Glut-1
      expression was accompanied by a massive augmentation in glucose uptake in TCR
      stimulated CD4 and CD8 lymphocytes. Finally, we determined that the apparent
      contradictory results obtained by Takenouchi et al were due to their monitoring
      of Glut-1 with a mAb that does not bind cells expressing endogenous Glut-1,
      including human erythrocytes that harbor 300,000 copies per cell. CONCLUSION:
      Transfection of Glut-1 directly correlates with the capacities of HTLV-1 and HTLV
      2 envelope-derived ligands to bind cells. Moreover, Glut-1 is induced by TCR
      engagement, resulting in massive increases in glucose uptake and binding of HTLV
      1 and -2 envelopes to both CD4 and CD8 T lymphocytes. Therefore, Glut-1 is a
      primary binding receptor for HTLV-1 and HTLV-2 envelopes on activated CD4 as well
      as CD8 lymphocytes.

PMID- 17504524
TI  - Mesenteric extraskeletal osteosarcoma with telangiectatic features: a case
      report.
AB  - BACKGROUND: Extraskeletal osteosarcoma is a rare malignant mesenchymal tumor,
      with a predominant occurrence in the extremities. Only two cases of mesenteric
      extraskeletal osteosarcoma have been documented. We describe an unusual case of
      extraskeletal osteosarcoma with telangiectatic features occurring in the
      mesentery. CASE PRESENTATION: A 67-year-old male presented with blood-tinged
      stool of 1-month's duration. On colonoscopy, a solid mass was detected protruding
      from the colon wall. Computed tomography showed a 15 x 9.7 cm heterogeneously
      enhancing mass, with mottled calcification and a cystic portion, occupying the
      left upper quadrant of the abdominal cavity. Curative resection of the tumor was
      performed, and the excised tumor was composed of large multilocular cysts
      containing old hematomas and necrotic debris. The histology revealed an
      osteosarcoma showing osteoid formation and blood-filled spaces lined with
      atypical cells. Despite postoperative chemotherapy, he developed a recurrent
      peritoneal mass and multiple lung metastases 3 months postoperatively.
      CONCLUSION: Given the rarity of cases of mesenteric extraskeletal osteosarcoma,
      its biologic behavior at this location remains to be determined. However,
      extraskeletal osteosarcoma with telangiectatic features is an uncommon entity to
      be recognized because of the possible fatal outcome related to the tumors.

PMID- 17504525
TI  - General Practitioners involvement in enteral tube feeding at home: a qualitative
      study.
AB  - BACKGROUND: Complex medical treatment is moving from hospital to primary care and
      General Practitioners (GPs) are increasingly asked to undertake new roles. There
      are now an estimated 19,500 patients being fed in the UK in the community on
      enteral tube feeding using a variety of different feeding tubes (Percutaneous
      endoscopic gastrostomy (PEG), Jejunostomy, or nasogastric (NG). The majority of
      patients are over the age of 65 years when they had artificial feeding initiated
      and mainly because of dysphagia. The aim of this study was to explore GPs
      knowledge, attitudes and skills relating to enteral feeding in the community.
      METHODS: Semi-structured one-to-one interviews with a convenience sample of GPs
      in Northern Ireland. RESULTS: Twenty-three GPs in three health boards in Northern
      Ireland participated in the study. Most found dealing with enteral feeding to be
      a predominantly negative experience. They had little involvement in patient
      selection for the procedure and poor or no discharge information. GPs felt
      inadequately trained, there was poor communication between primary and secondary
      care and little support. There was anger and frustration among GPs about lack of
      resources (funding and training), and the perception that primary care was used
      as a dumping ground. CONCLUSION: Moving complex medical treatment from secondary
      to primary care has major implications for GPs who should be included in the
      patient selection process, have adequate discharge information about their
      patients, be adequately resourced and have appropriate support and training.

PMID- 17504526
TI  - Gene expression and the evolution of phenotypic diversity in social wasps.
AB  - BACKGROUND: Organisms are capable of developing different phenotypes by altering
      the genes they express. This phenotypic plasticity provides a means for species
      to respond effectively to environmental conditions. One of the most dramatic
      examples of phenotypic plasticity occurs in the highly social hymenopteran
      insects (ants, social bees, and social wasps), where distinct castes and sexes
      all arise from the same genes. To elucidate how variation in patterns of gene
      expression affects phenotypic variation, we conducted a study to simultaneously
      address the influence of developmental stage, sex, and caste on patterns of gene
      expression in Vespula wasps. Furthermore, we compared the patterns found in this
      species to those found in other taxa in order to investigate how variation in
      gene expression leads to phenotypic evolution. RESULTS: We constructed 11
      different cDNA libraries derived from various developmental stages and castes of
      Vespula squamosa. Comparisons of overall expression patterns indicated that gene
      expression differences distinguishing developmental stages were greater than
      expression differences differentiating sex or caste. Furthermore, we determined
      that certain sets of genes showed similar patterns of expression in the same
      phenotypic forms of different species. Specifically, larvae upregulated genes
      related to metabolism and genes possessing structural activity. Surprisingly, our
      data indicated that at least a few specific gene functions and at least one
      specific gene family are important components of caste differentiation across
      social insect taxa. CONCLUSION: Despite research on various aspects of
      development originating from model systems, growth in understanding how
      development is related to phenotypic diversity relies on a growing literature of
      contrasting studies in non-model systems. In this study, we found that
      comparisons of patterns of gene expression with model systems highlighted areas
      of conserved and convergent developmental evolution across diverse taxa. Indeed,
      conserved biological functions across species implicated key functions related to
      how phenotypes are built. Finally, overall differences between social insect taxa
      suggest that the independent evolution of caste arose via distinct developmental
      trajectories.

PMID- 17504527
TI  - General practitioners' knowledge and practice of complementary/alternative
      medicine and its relationship with life-styles: a population-based survey in
      Italy.
AB  - BACKGROUND: The growing popularity of CAM among the public is coupled with an
      ongoing debate on its effectiveness, safety, and its implications on the
      reimbursement system. This issue is critically important for GPs, who have a
      "gatekeeping" role with respect to health care expenditure. GPs must be aware of
      medications' uses, limitations and possible adverse effects. Our objective was to
      explore GPs' knowledge of CAM and patterns of recommendation and practice, as
      well as the relationship between such patterns and GPs' life-styles. METHODS: A
      cross-sectional study was conducted in Tuscany, a region of central Italy. One
      hundred percent female GPs (498) and a 60% random sample of male GPs (1310)
      practising in the region were contacted through a self-administered postal
      questionnaire followed by a postal reminder and telephone interview. RESULTS:
      Overall response rate was 82.1%. Most respondents (58%) recommended CAM but a far
      smaller fraction (13%) practised it; yet 36% of CAM practitioners had no
      certificated training. Being female, younger age, practising in larger
      communities, having had some training in CAM as well as following a vegetarian or
      macrobiotic diet and doing physical activity were independent predictors of CAM
      recommendation and practice. However, 42% of GPs did not recommend CAM to
      patients mostly because of the insufficient evidence of its effectiveness.
      CONCLUSION: CAM knowledge among GPs is not as widespread as the public demand
      seems to require, and the scarce evidence of CAM effectiveness hinders its
      professional use among a considerable number of GPs. Sound research on CAM
      effectiveness is needed to guide physicians' behaviour, to safeguard patients'
      safety, and to assist policy-makers in planning regulations for CAM usage.

PMID- 17504529
TI  - Evolution of male genitalia: environmental and genetic factors affect genital
      morphology in two Drosophila sibling species and their hybrids.
AB  - BACKGROUND: The rapid evolution of genital morphology is a fascinating feature
      that accompanies many speciation events. However, the underlying patterns and
      explanatory processes remain to be settled. In this work we investigate the
      patterns of intraspecific variation and interspecific divergence in male
      genitalic morphology (size and shape) in the cactophilic sibling species
      Drosophila buzzatii and D. koepferae. Genital morphology in interspecific hybrids
      was examined and compared to the corresponding parental lines. RESULTS: Despite
      of being siblings, D. buzzatii and D. koepferae showed contrasting patterns of
      genital morphological variation. Though genitalic size and shape variation have a
      significant genetic component in both species, shape varied across host cacti
      only in D. buzzatii. Such plastic expression of genital shape is the first
      evidence of the effect of rearing substrate on genitalic morphology in
      Drosophila. Hybrid genital morphology was not intermediate between parental
      species and the morphological resemblance to parental strains was cross
      dependent. CONCLUSION: Our results suggest the evolution of different
      developmental networks after interspecific divergence and the existence of a
      complex genetic architecture, involving genetic factors with major effects
      affecting genital morphology.

PMID- 17504528
TI  - BRIP1 (BACH1) variants and familial breast cancer risk: a case-control study.
AB  - BACKGROUND: Inactivating and truncating mutations of the nuclear BRCA1
      interacting protein 1 (BRIP1) have been shown to be the major cause of Fanconi
      anaemia and, due to subsequent alterations of BRCA1 function, predispose to
      breast cancer (BC). METHODS: We investigated the effect of BRIP1 -64G>A and
      Pro919Ser on familial BC risk by means of TaqMan allelic discrimination,
      analysing BRCA1/BRCA2 mutation-negative index patients of 571 German BC families
      and 712 control individuals. RESULTS: No significant differences in genotype
      frequencies between BC cases and controls for BRIP1 -64G>A and Pro919Ser were
      observed. CONCLUSION: We found no effect of the putatively functional BRIP1
      variants -64G>A and Pro919Ser on the risk of familial BC.

PMID- 17504530
TI  - Equity in health and healthcare in Malawi: analysis of trends.
AB  - BACKGROUND: Growing scientific evidence points to the pervasiveness of inequities
      in health and health care and the persistence of the inverse care law, that is
      the availability of good quality healthcare seems to be inversely related to the
      need for it in developing countries. Achievement of the Millennium Development
      Goals is likely to be compromised if inequities in health/healthcare are not
      properly addressed. OBJECTIVE: This study attempts to assess trends in inequities
      in selected indicators of health status and health service utilization in Malawi
      using data from the Demographic and Health Surveys of 1992, 2000 and 2004.
      METHODS: Data from Demographic and Health Surveys of 1992, 2000 and 2004 are
      analysed for inequities in health/healthcare using quintile ratios and
      concentration curves/indices. RESULTS: Overall, the findings indicate that in
      most of the selected indicators there are pro-rich inequities and that they have
      been widening during the period under consideration. Furthermore, vertical
      inequities are observed in the use of interventions (treatment of diarrhoea, ARI
      among under-five children), in that the non-poor who experience less burden from
      these diseases receive more of the treatment/interventions, whereas the poor who
      have a greater proportion of the disease burden use less of the interventions. It
      is also observed that the publicly provided services for some of the selected
      interventions (e.g. child delivery) benefit the non-poor more than the poor.
      CONCLUSION: The widening trend in inequities, in particular healthcare
      utilization for proven cost-effective interventions is likely to jeopardize the
      achievement of the Millennium Development Goals and other national and regional
      targets. To counteract the inequities it is recommended that coverage in poor
      communities be increased through appropriate targeting mechanisms and effective
      service delivery strategies. There is also a need for studies to identify which
      service delivery mechanisms are effective in the Malawian context.

PMID- 17504531
TI  - A Cre-lox approach for transient transgene expression in neural precursor cells
      and long-term tracking of their progeny in vitro and in vivo.
AB  - BACKGROUND: Neural precursor cells (NPCs) can be isolated from various regions of
      the postnatal central nervous system (CNS). Manipulation of gene expression in
      these cells offers a promising strategy to manipulate their fate both in vitro
      and in vivo. In this study, we developed a technique that allows the transient
      manipulation of single/multiple gene expression in NPCs in vitro, and the long
      term tracking of their progeny both in vitro and in vivo. RESULTS: In order to
      combine the advantages of transient transfection with the long-term tracking of
      the transfected cells progeny, we developed a new approach based on the cre-lox
      technology. We first established a fast and reliable protocol to isolate and
      culture NPCs as monolayer, from the spinal cord of neonatal transgenic Rosa26-YFP
      cre-reporter mice. These cells could be reliably transfected with single/multiple
      plasmids by nucleofection. Nucleofection with mono- or bicistronic plasmids
      containing the Cre recombinase gene resulted in efficient recombination and the
      long-term expression of the YFP-reporter gene. The transient cre-expression was
      non-toxic for the transfected cells and did not alter their intrinsic properties.
      Finally, we demonstrated that cre-transfected cells could be transplanted into
      the adult brain, where they maintained YFP expression permitting long-term
      tracking of their migration and differentiation. CONCLUSION: This approach allows
      single/multiple genes to be manipulated in NPCs, while at the same time allowing
      long-term tracking of the transfected cells progeny to be analyzed both in vitro
      and in vivo.

PMID- 17504532
TI  - Antigen-presenting particle technology using inactivated surface-engineered
      viruses: induction of immune responses against infectious agents.
AB  - BACKGROUND: Developments in cell-based and gene-based therapies are emerging as
      highly promising areas to complement pharmaceuticals, but present day approaches
      are too cumbersome and thereby limit their clinical usefulness. These
      shortcomings result in procedures that are too complex and too costly for large
      scale applications. To overcome these shortcomings, we described a protein
      delivery system that incorporates over-expressed proteins into viral particles
      that are non-infectious and stable at room temperature. The system relies on the
      biological process of viral egress to incorporate cellular surface proteins while
      exiting their host cells during lytic and non-lytic infections. RESULTS: We
      report here the use of non-infectious surface-engineered virion particles to
      modulate immunity against three infectious disease agents--human immunodeficiency
      virus type 1 (HIV-1), herpes simplex virus (HSV), and Influenza. Surface
      engineering of particles are accomplished by genetic modification of the host
      cell surface that produces the egress budding viral particle. Human peripheral
      blood lymphocytes from healthy donors exposed to CD80/B7.1, CD86/B7.2, and/or
      antiCD3 single-chain antibody surface-engineered non-infectious HIV-1 and HSV-2
      particles stimulate T cell proliferation, whereas particles released from non
      modified host cells have no T cell stimulatory activity. In addition to T cell
      proliferation, HIV-based particles specifically suppress HIV-1 replication (both
      monocytotropic and lymphocytotropic strains) 55 to 96% and HSV-based particles
      specifically induce cross-reactive HSV-1/HSV-2 anti-herpes virus antibody
      production. Similar surface engineering of influenza-based particles did not
      modify the intrinsic ability of influenza particles to stimulate T cell
      proliferation, but did bestow on the engineered particles the ability to induce
      cross-strain anti-influenza antibody production. CONCLUSION: We propose that non
      infectious viral particles can be surface-engineered to produce antigen
      presenting particles that mimic antigen-presenting cells to induce immune
      responses in human peripheral blood lymphocytes. The viral particles behave as
      "biological carriers" for recombinant proteins, thereby establishing a new
      therapeutic paradigm for molecular medicine.

PMID- 17504533
TI  - Bonding of articular cartilage using a combination of biochemical degradation and
      surface cross-linking.
AB  - After trauma, articular cartilage often does not heal due to incomplete bonding
      of the fractured surfaces. In this study we investigated the ability of chemical
      cross-linkers to facilitate bonding of articular cartilage, either alone or in
      combination with a pre-treatment with surface-degrading agents. Articular
      cartilage blocks were harvested from the femoropatellar groove of bovine calves.
      Two cartilage blocks, either after pre-treatment or without, were assembled in a
      custom-designed chamber in partial apposition and subjected to cross-linking
      treatment. Subsequently, bonding of cartilage was measured as adhesive strength,
      that is, the maximum force at rupture of bonded cartilage blocks divided by the
      overlap area. In a first approach, bonding was investigated after treatment with
      cross-linking reagents only, employing glutaraldehyde, 1-ethyl-3-diaminopropyl
      carbodiimide (EDC)/N-hydroxysuccinimide (NHS), genipin, or transglutaminase.
      Experiments were conducted with or without compression of the opposing surfaces.
      Compression during cross-linking strongly enhanced bonding, especially when
      applying EDC/NHS and glutaraldehyde. Therefore, all further experiments were
      performed under compressive conditions. Combinations of each of the four cross
      linking agents with the degrading pre-treatments, pepsin, trypsin, and guanidine,
      led to distinct improvements in bonding compared to the use of cross-linkers
      alone. The highest values of adhesive strength were achieved employing
      combinations of pepsin or guanidine with EDC/NHS, and guanidine with
      glutaraldehyde. The release of extracellular matrix components, that is,
      glycosaminoglycans and total collagen, from cartilage blocks after pre-treatment
      was measured, but could not be directly correlated to the determined adhesive
      strength. Cytotoxicity was determined for all substances employed, that is,
      surface degrading agents and cross-linkers, using the resazurin assay. Taking the
      favourable cell vitality after treatment with pepsin and EDC/NHS and the
      cytotoxic effects of guanidine and glutaraldehyde into account, the combination
      of pepsin and EDC/NHS appeared to be the most advantageous treatment in this
      study. In conclusion, bonding of articular cartilage blocks was achieved by
      chemical fixation of their surface components using cross-linking reagents.
      Application of compressive forces and prior modulation of surface structures
      enhanced cartilage bonding significantly. Enzymatic treatment in combination with
      cross-linkers may represent a promising addition to current techniques for
      articular cartilage repair.

PMID- 17504534
TI  - Exon arrays provide accurate assessments of gene expression.
AB  - We have developed a strategy for estimating gene expression on Affymetrix Exon
      arrays. The method includes a probe-specific background correction and a probe
      selection strategy in which a subset of probes with highly correlated intensities
      across multiple samples are chosen to summarize gene expression. Our results
      demonstrate that the proposed background model offers improvements over the
      default Affymetrix background correction and that Exon arrays may provide more
      accurate measurements of gene expression than traditional 3' arrays.

PMID- 17504535
TI  - Acute and long-term survival in chronically critically ill surgical patients: a
      retrospective observational study.
AB  - INTRODUCTION: Various cohort studies have shown that acute (short-term) mortality
      rates in unselected critically ill patients may have improved during the past 15
      years. Whether these benefits also affect acute and long-term prognosis in
      chronically critically ill patients is unclear, as are determinants relevant to
      prognosis. METHODS: We conducted a retrospective analysis of data collected from
      March 1993 to February 2005. A cohort of 390 consecutive surgical patients
      requiring intensive care therapy for more than 28 days was analyzed. RESULTS: The
      intensive care unit (ICU) survival rate was 53.6%. Survival rates at one, three
      and five years were 61.8%, 44.7% and 37.0% among ICU survivors. After adjustment
      for relevant covariates, acute and long-term survival rates did not differ
      significantly between 1993 to 1999 and 1999 to 2005 intervals. Acute prognosis
      was determined by disease severity during ICU stay and by primary diagnosis.
      However, only the latter was independently associated with long-term prognosis.
      Advanced age was an independent prognostic determinant of poor short-term and
      long-term survival. CONCLUSION: Acute and long-term prognosis in chronically
      critically ill surgical patients has remained unchanged throughout the past 12
      years. After successful surgical intervention and intensive care, long-term
      outcome is reasonably good and is mainly determined by age and underlying
      disease.

PMID- 17504536
TI  - A decision aid for COPD patients considering inhaled steroid therapy: development
      and before and after pilot testing.
AB  - BACKGROUND: Decision aids (DA) are tools designed to help patients make specific
      and deliberative choices among disease management options. DAs can improve the
      quality of decision-making and reduce decisional conflict. An area not covered by
      a DA is the decision of a patient with chronic obstructive pulmonary disease
      (COPD) to use inhaled steroids which requires balancing the benefits and
      downsides of therapy. METHODS: We developed a DA for COPD patients considering
      inhaled steroid therapy using the Ottawa Decision Support Framework, the best
      available evidence for using inhaled steroid in COPD and the expected utility
      model. The development process involved patients, pulmonologists, DA developers
      and decision making experts. We pilot tested the DA with 8 COPD patients who
      completed an evaluation questionnaire, a knowledge scale, and a validated
      decisional conflict scale. RESULTS: The DA is a computer-based interactive tool
      incorporating four different decision making models. In the first part, the DA
      provides information about COPD as a disease, the different treatment options,
      and the benefits and downsides of using inhaled steroids. In the second part, it
      coaches the patient in the decision making process through clarifying values and
      preferences. Patients evaluated 10 out of 13 items of the DA positively and
      showed significant improvement on both the knowledge scale (p = 0.008) and the
      decisional conflict scale (p = 0.008). CONCLUSION: We have developed a computer
      based interactive DA for COPD patients considering inhaled steroids serving as a
      model for other DAs in COPD, in particular related to inhaled therapies. Future
      research should assess the DA effectiveness.

PMID- 17504537
TI  - TAP score: torsion angle propensity normalization applied to local protein
      structure evaluation.
AB  - BACKGROUND: Experimentally determined protein structures may contain errors and
      require validation. Conformational criteria based on the Ramachandran plot are
      mainly used to distinguish between distorted and adequately refined models. While
      the readily available criteria are sufficient to detect totally wrong structures,
      establishing the more subtle differences between plausible structures remains
      more challenging. RESULTS: A new criterion, called TAP score, measuring local
      sequence to structure fitness based on torsion angle propensities normalized
      against the global minimum and maximum is introduced. It is shown to be more
      accurate than previous methods at estimating the validity of a protein model in
      terms of commonly used experimental quality parameters on two test sets
      representing the full PDB database and a subset of obsolete PDB structures.
      Highly selective TAP thresholds are derived to recognize over 90% of the top
      experimental structures in the absence of experimental information. Both a web
      server and an executable version of the TAP score are available at
      http://protein.cribi.unipd.it/tap/. CONCLUSION: A novel procedure for energy
      normalization (TAP) has significantly improved the possibility to recognize the
      best experimental structures. It will allow the user to more reliably isolate
      problematic structures in the context of automated experimental structure
      determination.

PMID- 17504538
TI  - Neuropsychological patterns in systemic lupus erythematosus patients with
      depression.
AB  - Thirteen patients with systemic lupus erythematosus and depression (Depressed
      SLE), 10 Depressed-Control subjects, and 25 Healthy Control subjects completed
      cognitive testing and self-report questionnaires of pain, depression, and
      fatigue. The Depressed-SLE group scored higher on the American College of
      Rheumatology Neuropsychological Battery for systemic lupus erythematosus
      cognitive impairment index compared to Depressed-Control and Healthy Control
      subjects (p < 0.05 and p < 0.02, respectively). No correlations between cognitive
      impairment and pain, fatigue, or perceived cognitive failures were observed in
      the Depressed-SLE participants. Moderate agreement (86.4%) was found between a
      comprehensive neuropsychology battery cognitive impairment index and the ACR-SLE
      impairment index in the Depressed-SLE patients. Overall, the magnitude and
      pattern of cognitive impairment in Depressed-SLE patients cannot be explained by
      depression alone.

PMID- 17504539
TI  - Characterization of hypothetical proteins Cpn0146, 0147, 0284 & 0285 that are
      predicted to be in the Chlamydia pneumoniae inclusion membrane.
AB  - BACKGROUND: Although more than 100 Chlamydia pneumoniae hypothetical proteins
      have been predicted to be inclusion membrane proteins, only a few have been
      experimentally demonstrated to be in the inclusion membrane. Using antibodies
      raised with fusion proteins, we characterized four such hypothetical proteins
      encoded by two gene clusters (Cpn0146-147 and Cpn0284-285) in the C. pneumoniae
      genome. RESULTS: Cpn0146 and 0147 were detected in the inclusion membrane while
      Cpn0284 and 0285 inside inclusion and mainly associated with reticulate bodies
      although all four proteins contain an N-terminal bi-lobed hydrophobic region, a
      signature motif assigned to inclusion membrane proteins. These four hypothetical
      proteins were only detected in cells infected with C. pneumoniae but not other
      chlamydial species, with Cpn0147 at 6 hours and Cpn0146, 0284 & 0285 at 24 hours
      after infection. Cpn0146 & 147 but not Cpn0284 and 285 co-localized with a host
      cell endoplasmic reticulum marker, a property known to be possessed by some
      chlamydial inclusion membrane proteins, when expressed in the host cell cytosol
      via transgenes. However, the endoplasmic reticulum localization of the C.
      pneumoniae inclusion membrane proteins did not result in inhibition of the
      subsequent C. pneumoniae infection. CONCLUSION: The hypothetical proteins Cpn0146
      & 0147 were localized in the C. pneumoniae inclusion membrane while Cpn0284 &
      0285 within the inclusion although all four were predicted to be Inc proteins,
      suggesting the need to experimentally characterize the predicted Inc proteins.

PMID- 17504540
TI  - Differential effectiveness of residential versus outpatient aftercare for
      parolees from prison-based therapeutic community treatment programs.
AB  - BACKGROUND: Research has indicated that more intense treatment is associated with
      better outcomes among clients who are appropriately matched to treatment
      intensity level based on the severity of their drug/alcohol problem. This study
      examined the differential effectiveness of community-based residential and
      outpatient treatment attended by male and female drug-involved parolees from
      prison-based therapeutic community substance abuse treatment programs based on
      the severity of their drug/alcohol problem. METHODS: Subjects were 4,165 male and
      female parolees who received prison-based therapeutic community substance abuse
      treatment and who subsequently participated in only outpatient or only
      residential treatment following release from prison. The dependent variable of
      interest was return to prison within 12 months. The primary independent variables
      of interest were alcohol/drug problem severity (low, high) and type of aftercare
      (residential, outpatient). Chi-square analyses were conducted to examine the
      differences in 12-month RTP rates between and within the two groups of parolees
      (residential and outpatient parolees) based on alcohol/drug problem severity (low
      severity, high severity). Logistic regression analyses were performed to
      determine if aftercare modality (outpatient only vs. residential only) was a
      significant predictor of 12-month RTP rates for subjects who were classified as
      low severity versus those who were classified as high severity. RESULTS: Subjects
      benefited equally from outpatient and residential aftercare, regardless of the
      severity of their drug/alcohol problem. CONCLUSION: As states and the federal
      prison system further expand prison-based treatment services, the demand and
      supply of aftercare treatment services will also increase. As this occurs,
      systems and policies governing the transitioning of individuals from prison- to
      community-based treatment should include a systematic and validated assessment of
      post-prison treatment needs and a valid and reliable means to assess the quality
      of community-based treatment services. They should also ensure that parolees
      experience a truly uninterrupted continuum of care through appropriate
      recognition of progress made in prison-based treatment.

PMID- 17504541
TI  - Teaching medical students about children with disabilities in a rural setting in
      a school.
AB  - BACKGROUND: To describe and implement a community paediatric placement in a
      school setting that teaches undergraduate medical students about intellectual
      disability that provides benefit to the community and is acceptable to both
      students and teachers. METHODS: Twenty six 4th year undergraduate medical
      students of the University of Newcastle completed their Paediatric studies based
      in Tamworth in 2004 & 2005 including an 8 week placement at Bullimbal School for
      Specific Purposes. The placement involved the students being actively involved in
      assisting with the delivery of a variety of activities aimed at improving the
      motor skills of a group of disabled children. De-identified data were obtained
      from completed evaluation surveys from 75% (21 of 26) of the medical students and
      from 100% (5 of 5) of the teachers. RESULTS: All students and teachers found the
      placement was acceptable and enjoyed the placement and felt that it gave the
      medical students a greater understanding of children with disabilities. 80% (4 of
      5) of the teachers involved in the program did not feel that its implementation
      added to their workload and all were enthusiastic to continue with the program.
      CONCLUSION: Medical students can be effectively taught and have a valuable
      clinical experience in a school setting to learn about children with a
      disability. This educational innovation has provided a mutual benefit for both
      the medical students and the school children who participated in the program
      without impacting on the workloads of teachers.

PMID- 17504542
TI  - Reproductive health of male Australian veterans of the 1991 Gulf War.
AB  - BACKGROUND: Since the 1991 Gulf War concerns have been raised about the effects
      of deployment to the Gulf War on veterans' health. Studies of the reproductive
      health of Gulf War veterans have reported varied findings. METHODS: We undertook
      a cross-sectional study of male Australian Gulf War veterans (n = 1,424) and a
      randomly sampled military comparison group (n = 1,548). The study was conducted
      from August 2000 to April 2002. A postal questionnaire included questions about
      difficulties achieving pregnancy, pregnancy outcomes including live births,
      stillbirths, miscarriages and terminations; and for all live births gestation,
      birth weight, sex, and any cancers, birth defects, chromosomal abnormalities or
      serious health problems. RESULTS: Male Gulf War veterans reported slightly
      increased risk of fertility difficulties following the Gulf War (odds ratio [OR]
      1.4; 95% confidence interval [CI] 1.0-1.8), but were more successful at
      subsequently fathering a child (OR 1.8; 95% CI 1.3-2.6). The study groups
      reported similar rates of pregnancies and live births. There was no increased
      risk in veterans of miscarriage, stillbirth, or terminations. Children of male
      Gulf War veterans born after the period of the Gulf War were not at greater risk
      of being born prematurely, having a low birth weight, or having a birth defect or
      chromosomal abnormality (OR 1.0; 95% CI 0.6-1.6). The numbers of cancers and
      deaths in children were too small to draw any firm conclusions. CONCLUSION: The
      results of this study do not show an increased risk of adverse reproductive
      outcome in Australian male Gulf War veterans.

PMID- 17504543
TI  - Immediate and short-term pain relief by acute sciatic nerve press: a randomized
      controlled trial.
AB  - BACKGROUND: Despite much research, an immediately available, instantly effective
      and harmless pain relief technique has not been discovered. This study describes
      a new manipulation: a "2-minute sciatic nerve press", for rapid short-term relief
      of pain brought on by various dental and renal diseases. METHODS: This
      randomized, single-blind, placebo-controlled trial ran in three hospitals in
      Anhui Province, China, with an enrollment of 66 out of 111 solicited patients
      aged 16 to 74 years. Patients were recruited sequentially, by specific
      participating physicians at their clinic visits to three independent hospitals.
      The diseases in enrolled dental patients included dental caries, periodontal
      diseases and dental trauma. Renal diseases in recruits included kidney
      infections, stones and some other conditions. Patients were randomly assigned to
      receive the "2-minute sciatic nerve press" or the "placebo press". For the "2
      minute sciatic nerve press", pressure was applied simultaneously to the sciatic
      nerves at the back of the thighs, using the fists while patients lay prone. For
      the "placebo press", pressure was applied simultaneously to a parallel spot on
      the front of the thighs, using the fists while patients lay supine. Each fist
      applied a pressure of 11 to 20 kg for 2 minutes, after which, patients arose to
      rate pain. RESULTS: The "2-minute sciatic nerve press" produced greater pain
      relief than the "placebo press". Within the first 10 minutes after sciatic
      pressure, immediate pain relief ratings averaged 66.4% (p < 0.001) for the dental
      patients, versus pain relief of 20% for the placebo press, and, 52.2% (p < 0.01)
      for the renal patients, versus relief of 14% for the placebo press, in median.
      The method worked excellently for dental caries and periodontal diseases, but
      poorly for dental trauma. Forty percent of renal patients with renal colic did
      not report any pain relief after the treatment. CONCLUSION: Two minutes of
      pressure on both sciatic nerves can produce immediate significant conduction
      analgesia, providing a convenient, safe and powerful way to overcome clinical
      pain brought on by dental diseases and renal diseases for short term purposes.
      TRIAL REGISTRATION: ACTR 12606000439549.

PMID- 17504545
TI  - Guidelines for safety and quality in anaesthesia practice in the European Union.
AB  - Anaesthesia is a medical specialty that is particularly concerned with the safety
      of the patient who is undergoing a surgical procedure. This is a prerequisite in
      order to provide quality of care, which is based on good clinical practice, on a
      sound organization, on an agreement on best practice and on adequate
      communication with other healthcare workers involved. Providing a safe
      environment for those working in healthcare is at least as important as other
      factors serving that objective. A working party on Safety and Quality in
      Anaesthesiological Practice in the Section and Board of Anaesthesiology of the
      European Union of Medical Specialists (EUMS/UEMS) has prepared guidelines that
      were amended and approved recently.

PMID- 17504544
TI  - A distance difference matrix approach to identifying transcription factors that
      regulate differential gene expression.
AB  - We introduce a method that considers target genes of a transcription factor, and
      searches for transcription factor binding sites (TFBSs) of secondary factors
      responsible for differential responses among these targets. Based on the distance
      difference matrix concept, the method simultaneously integrates statistical
      overrepresentation and co-occurrence of TFBSs. Our approach is validated on
      datasets of differentially regulated human genes and is shown to be highly
      effective in detecting TFBSs responsible for the observed differential gene
      expression.

PMID- 17504546
TI  - Mental models of learning in distance education.
AB  - BACKGROUND: Interview-based research has shown that students in higher education
      hold a number of different conceptions of learning and of themselves as learners.
      There is debate about whether these conceptions constitute a developmental
      hierarchy. AIMS: This study evaluated the Mental Models section of Vermunt and
      van Rijswijk's (1988) Inventory of Learning Styles (ILS) as a measure of
      students' conceptions of learning and sought to identify conceptions of learning
      as qualitatively different patterns of scores. SAMPLE: A random sample of 1,000
      students who were taking courses by distance learning with the Open University in
      the UK. METHOD: A translated and adapted version of the Mental Models section of
      the ILS was administered in a postal survey. Complete data were obtained from 441
      students and were subjected to principal component analysis, cluster analysis and
      discriminant analysis. RESULTS: The five scales in the Mental Models section of
      the ILS were homogeneous and achieved a satisfactory level of internal
      consistency, but two of the five scales could not be differentiated from each
      other in the students' responses. A cluster analysis identified four subgroups of
      students who had different patterns of scores on two discriminant functions.
      CONCLUSION: The four mental models identified in this study were broadly similar
      to those identified by Vermunt (1996) in an interview-based study. However, these
      do not seem to constitute a developmental hierarchy, and, following Vermunt, it
      is suggested that they are better interpreted as aspects of four over-arching
      'learning styles' or 'learning patterns'.

PMID- 17504547
TI  - Collaborative philosophical enquiry for school children: cognitive effects at 10
      12 years.
AB  - BACKGROUND: Debates about the modifiability of cognitive ability have been
      largely resolved by reports of successful 'thinking skills' interventions.
      However, such interventions are very diverse and generalization of effects
      relatively little explored. AIMS: This study investigated whether a thinking
      skills intervention involving collaborative interactive dialogue could lead not
      only to gains in measured verbal cognitive ability but also generalization to non
      verbal and quantitative reasoning ability. SAMPLE: Randomly selected intervention
      children were aged 10 at pre-test (N=105, four classes/schools). Controls
      followed a normal curriculum (N=72, three classes/two schools). METHOD:
      Intervention children engaged in collaborative enquiry for 1 hour per week over
      16 months. The control group received normal classroom experiences. The Cognitive
      Abilities Test was administered before and after the intervention. RESULTS:
      Intervention pupils showed significant standardized gains in verbal and also in
      non-verbal and quantitative aspects of reasoning, consistent across intervention
      schools. Boys and girls made significant gains. The highest quartile of pre-test
      ability showed the smallest gains. Controls did not gain in any aspect.
      CONCLUSIONS: Philosophical enquiry involving interactive dialogue led not only to
      significant gains in measured verbal cognitive ability but also generalization to
      non-verbal and quantitative reasoning ability, consistent across schools and
      largely irrespective of pupil gender and ability. The effect sizes from this
      large-scale field trial in one local authority exceeded those reported in the
      literature. Implications for theory building, replicability and sustainability
      are addressed.

PMID- 17504548
TI  - Classroom interactions: exploring the practices of high- and low-expectation
      teachers.
AB  - BACKGROUND: Early research exploring teacher expectations concentrated on the
      dyadic classroom interactions of teachers with individual students. More recent
      studies have shown whole class factors to have more significance in portraying
      teachers' expectations. Recently teachers having high or low expectations for all
      their students have been identified. AIMS: The aim of the current investigation
      was to explore whether the classroom exchanges of high- and low-expectation
      teachers differed substantially and might be considered a mechanism for teachers'
      expectations. SAMPLE: The participants were 12 primary school teachers from eight
      schools who had been identified as having expectations for their students'
      learning that were either significantly above or below the children's achievement
      level. The teachers formed three groups called high-expectation, low-expectation
      and average-progress teachers. METHOD: The participants were observed twice in
      the academic year during half-hour reading lessons. Two people observed each
      lesson, one completing a structured observation protocol and the other a running
      record and audiotape. RESULTS: In contrast to the average progress and low
      expectation teachers, the high-expectation teachers spent more time providing a
      framework for students' learning, provided their students with more feedback,
      questioned their students using more higher-order questions, and managed their
      students' behaviour more positively. CONCLUSIONS: There appear to be important
      differences in the classroom environments for the students of high-expectation,
      average-progress and low-expectation teachers. The differences apply to both the
      instructional and socioemotional environments of the classroom. Such disparities
      may act as mechanisms for teacher expectation effects.

PMID- 17504549
TI  - Pupils' over-reliance on linearity: a scholastic effect?
AB  - BACKGROUND: From upper elementary education on, children develop a tendency to
      over-use linearity. Particularly, it is found that many pupils assume that if a
      figure enlarges k times, the area enlarges k times too. However, most research
      was conducted with traditional, school-like word problems. AIMS: This study
      examines whether pupils also over-use linearity if non-linear problems are
      embedded in meaningful, authentic performance tasks instead of traditional,
      school-like word problems, and whether this experience influences later
      behaviour. SAMPLE: Ninety-three sixth graders from two primary schools in
      Flanders, Belgium. METHOD: Pupils received a pre-test with traditional word
      problems. Those who made a linear error on the non-linear area problem were
      subjected to individual interviews. They received one new non-linear problem, in
      the S-condition (again a traditional, scholastic word problem), D-condition (the
      same word problem with a drawing) or P-condition (a meaningful performance-based
      task). Shortly afterwards, pupils received a post-test, containing again a non
      linear word problem. RESULTS: Most pupils from the S-condition displayed linear
      reasoning during the interview. Offering drawings (D-condition) had a positive
      effect, but presenting the problem as a performance task (P-condition) was more
      beneficial. Linear reasoning was nearly absent in the P-condition. Remarkably, at
      the post-test, most pupils from all three groups again applied linear strategies.
      CONCLUSIONS: Pupils' over-reliance on linearity seems partly elicited by the
      school-like word problem format of test items. Pupils perform much better if non
      linear problems are offered as performance tasks. However, a single experience
      does not change performances on a comparable word problem test afterwards.

PMID- 17504550
TI  - Stereotype threat in classroom settings: the interactive effect of domain
      identification, task difficulty and stereotype threat on female students' maths
      performance.
AB  - BACKGROUND: Stereotype threat research revealed that negative stereotypes can
      disrupt the performance of persons targeted by such stereotypes. This paper
      contributes to stereotype threat research by providing evidence that domain
      identification and the difficulty level of test items moderate stereotype threat
      effects on female students' maths performance. AIMS: The study was designed to
      test theoretical ideas derived from stereotype threat theory and assumptions
      outlined in the Yerkes-Dodson law proposing a nonlinear relationship between
      arousal, task difficulty and performance. SAMPLE: Participants were 108 high
      school students attending secondary schools. METHOD: Participants worked on a
      test comprising maths problems of different difficulty levels. Half of the
      participants learned that the test had been shown to produce gender differences
      (stereotype threat). The other half learned that the test had been shown not to
      produce gender differences (no threat). The degree to which participants identify
      with the domain of maths was included as a quasi-experimental factor. RESULTS:
      Maths-identified female students showed performance decrements under conditions
      of stereotype threat. Moreover, the stereotype threat manipulation had different
      effects on low and high domain identifiers' performance depending on test item
      difficulty. On difficult items, low identifiers showed higher performance under
      threat (vs. no threat) whereas the reverse was true in high identifiers. This
      interaction effect did not emerge on easy items. CONCLUSIONS: Domain
      identification and test item difficulty are two important factors that need to be
      considered in the attempt to understand the impact of stereotype threat on
      performance.

PMID- 17504551
TI  - Perceptions of athletic competence and fear of negative evaluation during
      physical education.
AB  - BACKGROUND: Physical education (PE) aims to enhance self-esteem, develop sporting
      interests and to encourage a physically active life-style. However, little is
      known about how a fear of negative evaluation (FNE), the socially evaluative
      aspect of social anxiety, affects children's attitudes to PE. AIM: The aim of the
      study was to investigate the relationships between perceived athletic competence
      and FNE within PE lessons, specifically looking at differences between boys and
      girls and primary and secondary schools. SAMPLE: The participants were 192
      children in three primary schools (N=85, mean age=9.5+/-1.1 years) and two
      secondary schools (N=107, mean age=14.5+/-0.8 years) from rural areas of North
      Wales and the Midlands region of England. METHODS: The participants completed the
      Brief-FNE Scale and the Self-Perception Profile for Children immediately post
      lesson on one occasion. RESULTS: Girls had higher FNE but lower perceptions of
      athletic competence than did boys. Older girls had higher FNE and lower perceived
      competence than the remaining three groups. Additionally, a significant and
      reverse but weak correlation was observed between girls' perceived athletic
      competence and FNE. CONCLUSIONS: The findings suggest that girls with a high FNE
      report lower perceptions of their athletic competence. Individuals who are high
      in FNE behave in ways to avoid the prospect of being evaluated negatively.
      However, they may seek feedback from significant others as a signal that
      unfavourable evaluations have been avoided. Therefore, positive, encouraging
      feedback used in child-centred learning strategies may foster feelings of
      competence in boys and girls and could reduce the girls' social anxiety.

PMID- 17504552
TI  - Examining the validity of self-reports on scales measuring students' strategic
      processing.
AB  - BACKGROUND: Self-report inventories trying to measure strategic processing at a
      global level have been much used in both basic and applied research. However, the
      validity of global strategy scores is open to question because such inventories
      assess strategy perceptions outside the context of specific task performance.
      AIMS: The primary aim was to examine the criterion-related and construct validity
      of the global strategy data obtained with the Cross-Curricular Competencies (CCC)
      scale. Additionally, we wanted to compare the validity of these data with the
      validity of data obtained with a task-specific self-report inventory focusing on
      the same types of strategies. SAMPLE: The sample included 269 10th-grade students
      from 12 different junior high schools. METHODS: Global strategy use as assessed
      with the CCC was compared with task-specific strategy use reported in three
      different reading situations. Moreover, relationships between scores on the CCC
      and scores on measures of text comprehension were examined and compared with
      relationships between scores on the task-specific strategy measure and the same
      comprehension measures. RESULTS: The comparison between the CCC strategy scores
      and the task-specific strategy scores suggested only modest criterion-related
      validity for the data obtained with the global strategy inventory. The CCC
      strategy scores were also not related to the text comprehension measures,
      indicating poor construct validity. In contrast, the task-specific strategy
      scores were positively related to the comprehension measures, indicating good
      construct validity. CONCLUSION: Attempts to measure strategic processing at a
      global level seem to have limited validity and utility.

PMID- 17504553
TI  - Do undergraduates' motives for studying change as they progress through their
      degrees?
AB  - BACKGROUND: Research has suggested that students can approach their studies with
      different goals, one goal being to understand material (mastery) and another to
      obtain better grades than others (performance). AIM: The main aim of this study
      was to assess whether these goals change as students progress through their
      degrees. SAMPLE: 1857 students at a Scottish university. METHODS: Students were
      asked to complete a questionnaire as they waited to register for their courses.
      The questionnaire was based on an achievement motivation questionnaire developed
      by Elliot and McGregor (2001) to assess students' mastery and performance goals;
      there were also questions on students' expectations about their courses. RESULTS:
      Students in years 2, 3 and 4 were substantially less likely to want to master
      their subjects than students in year 1. They were also more concerned with grades
      and less likely to expect to enjoy their courses. CONCLUSION: The decline in
      students' motivation to master their subjects raises potentially important
      questions about whether pressures for grades undermine students' interest in
      their studies.

PMID- 17504554
TI  - 'Ain't nothin' like the real thing'. Motivation and study processes on a work
      based project course in information systems design.
AB  - BACKGROUND: Advocates of the project method claim that project-based learning
      inspires student learning. However, it has been claimed that project-based
      learning environments demand quite a bit of self-regulation on the part of the
      learner. AIMS: Consequently, it was tested whether students scoring low in self
      regulation of learning experienced 'friction', an incompatibility between student
      self-regulation and the demands posed by the learning environment. This would be
      manifest in cognitive processing and motivation. SAMPLES: The target group
      consisted of 58 mainly third-year Finnish university students taking a mandatory
      project course in information systems design. During the project course, student
      teams completed a commissioned assignment. The study also included a matched
      nonequivalent comparison group composed of computer science students attending
      study programmes without a project-based component. METHODS: Data were gathered
      by means of a questionnaire administered at the beginning and end of the project
      course and it was analysed by between-groups repeated measures ANOVA. In
      addition, the students on the course were interviewed. RESULTS: Results suggest
      that the work-based project model in question may indeed have a substantial
      motivational impact, interestingly benefitting especially those students who
      scored low in self-regulation. CONCLUSIONS: It is argued that we tend to view
      learning environments too simplistically. In particular, a basic distinction
      should be made between individual and collaborative learning contexts, since peer
      scaffolding, group grading and choice of group roles may explain why students
      scoring low in self-regulation of learning did not encounter friction as
      expected.

PMID- 17504555
TI  - Examining a multidimensional model of student motivation and engagement using a
      construct validation approach.
AB  - BACKGROUND: This study seeks to examine a multidimensional model of student
      motivation and engagement using within- and between-network construct validation
      approaches. AIMS: The study tests the first- and higher-order factor structure of
      the motivation and engagement wheel and its corresponding measurement tool, the
      Motivation and Engagement Scale - High School (MES-HS; formerly the Student
      Motivation and Engagement Scale). SAMPLE: The study draws upon data from 12,237
      high school students from 38 Australian high schools. METHODS: The hypothesized
      11-factor first-order structure and the four-factor higher-order structure, their
      relationship with a set of between-network measures (class participation,
      enjoyment of school, educational aspirations), factor invariance across gender
      and year-level, and the effects of age and gender are examined using confirmatory
      factor analysis and structural equation modelling. RESULTS: In terms of within
      network validity, (1) the data confirm that the 11-factor and higher-order factor
      models of motivation and engagement are good fitting and (2) multigroup tests
      showed invariance across gender and year levels. In terms of between-network
      validity, (3) correlations with enjoyment of school, class participation and
      educational aspirations are in the hypothesized directions, and (4) girls reflect
      a more adaptive pattern of motivation and engagement, and year-level findings
      broadly confirm hypotheses that middle high school students seem to reflect a
      less adaptive pattern of motivation and engagement. CONCLUSION: The first- and
      higher-order structures hold direct implications for educational practice and
      directions for future motivation and engagement research.

PMID- 17504556
TI  - Bullies and victims at school: are they the same pupils?
AB  - BACKGROUND: The reported prevalence of bully-victims and aggressive/provocative
      victims varies quite considerably in previous research, and only a few studies
      have reported prevalence rates across grades. There is also a lack of detailed
      analyses of the extent to which victims are also bullies, and bullies are also
      victims. AIMS: To study the prevalence of male and female bully-victims across
      grade/age and to establish the degree of overlap or relative size of the bully
      victim group by relating them to all victims, all bullies and all involved
      students. SAMPLES: Participants in Study 1 were 5,171 pupils in grades 5-9 from
      37 schools. Study 2 comprised 12,983 pupils in grades 4-10 from 66 schools.
      METHODS: The Olweus Bully/Victim Questionnaire was administered to the pupils in
      their ordinary classrooms. RESULTS: The prevalence of bully-victims was low and
      mainly declined across grades. There were far more boys than girls in the bully
      victim group. Bully-victims resembled victims only (pure victims) in terms of age
      trends and bullies only (pure bullies) in terms of sex composition. The overlap
      of bully-victims with the total victim group was fairly small (10-20%) in all
      grades. In primary grades, bully-victims constituted about 30-50% of the total
      bully group, whereas in higher grades these proportions were considerably lower.
      CONCLUSION: Our analyses and overview of previous research suggest that the bully
      victim group is small, and that the large variations across studies are mainly
      due to differences in choice of cutoff point. Bully-victims should generally be
      seen and treated statistically as a distinct subgroup. The relatively larger
      proportion of bully-victims in lower grades should be explored further.

PMID- 17504557
TI  - School violence and teacher professional disengagement.
AB  - BACKGROUND: Most studies of school violence have focused on students.
      Consequently, precursors and consequences of violence experienced by teachers are
      less well documented. Previous research indicates that (a) verbal victimization,
      student misbehaviour and perceived violence at school impair teacher emotional
      well-being, (b) support from principal and colleagues reduces these difficulties
      and fosters well-being, (c) well-being impacts on professional involvement.
      However, it is still not clear how those variables relate to each other. AIMS: To
      test and compare - through structural equation modelling - two models of the
      relationships between perceived school support, exposure to school violence,
      subjective well-being and professional disengagement. To test - through
      multigroup analysis - the buffering effect of school support between school
      violence and well-being. SAMPLE: Participants in this study were 487 French
      speaking teachers (57% female) randomly selected from 24 secondary schools in
      Belgium. METHOD: Participants completed a questionnaire on school leadership,
      relationships with colleagues, verbal victimization, students' misbehaviour,
      perceived violence, depression, somatization, anxiety and professional
      disengagement. RESULTS: The results support a model in which perceived school
      support has a direct effect on exposure to school violence, subjective well-being
      and professional disengagement, while the effect of school violence on
      disengagement is totally mediated by well-being. No evidence of a moderating
      effect of school support was found. CONCLUSIONS: The results of this study
      suggest that the negative emotional impact of some forms of school violence could
      be an important factor in a teacher's intention to leave, and that school support
      could be even more important for both teacher emotional well-being and
      professional disengagement.

PMID- 17504558
TI  - A comparison of keyboarded and handwritten compositions and the relationship with
      transcription speed.
AB  - BACKGROUND: It is well established that handwriting fluency constrains writing
      quality by limiting resources for higher order processes such as planning and
      reviewing. According to the 'simple view of writing' then slow keyboarding speed
      should hinder the quality of keyboarded essay compositions in the same way that
      slow handwriting hinders handwritten essay compositions. Given a lack of touch
      typing instruction in UK schools it was hypothesized that children's written
      compositions produced via the keyboard would be worse than produced by hand.
      AIMS: To extend the work of Christensen (2004) and Rogers and Case-Smith (2002)
      by examining the relationship between handwriting fluency and keyboarding fluency
      throughout the primary school and studying the link between word-processed
      compositional quality and keyboarding fluency. SAMPLES AND METHODS: The
      handwriting fluency and keyboarding fluency of 300 children in primary school
      were measured. Year 5 and year 6 children completed a measure of compositional
      quality by hand and by keyboard. RESULTS AND COMMENT: There was a high
      correlation between handwriting and keyboarding speed and handwriting speed was
      consistently faster than keyboarding speed across all ages. Only a small minority
      of children in years 5 and 6 had faster keyboarding than handwriting speed.
      Results showed that children's compositional quality was superior in the
      handwritten scripts as opposed to the keyboarded scripts. Keyboarded scripts were
      up to 2 years behind handwritten scripts in development. Writing by keyboard does
      not necessarily lead to improvements in script quality, compared with handwritten
      scripts. Explicit keyboarding instruction (touch-typing) is needed to develop
      keyboarding fluency and unlock the full potential of the word processor for
      children's writing.

PMID- 17504563
TI  - Peak alignment and robust principal component analysis of gas chromatograms of
      fatty acid methyl esters and volatiles.
AB  - Gas chromatograms of fatty acid methyl esters and of volatile lipid oxidation
      products from fish lipid extracts are analyzed by multivariate data analysis
      [principal component analysis (PCA)]. Peak alignment is necessary in order to
      include all sampled points of the chromatograms in the data set. The ability of
      robust algorithms to deal with outlier problems, including both sample-wise and
      element-wise outliers, and the advantages and drawbacks of two robust PCA
      methods, robust PCA (ROBPCA) and robust singular value decomposition when
      analysing these GC data were investigated. The results show that the usage of
      ROPCA is advantageous, compared with traditional PCA, when analysing the entire
      profile of chromatographic data in cases of sub-optimally aligned data. It also
      demonstrates how choosing the most robust PCA (sample or element-wise) depends on
      the type of outliers present in the data set.

PMID- 17504564
TI  - Purification of secoisolariciresinol diglucoside with column chromatography on a
      sephadex LH-20.
AB  - A simplified and efficient method is developed for the large-scale purification
      of the secoisolariciresinol diglucoside (SDG) from defatted flaxseed after
      aqueous ethanol extraction. Extractant from defatted flaxseed with aqueous
      ethanol is hydrolyzed with basic solution, concentrated under vacuum, subjected
      to Sephadex LH-20 column chromatography, and eluted with aqueous ethanol of
      different concentrations. Elution is monitored by a UV detector at 280 nm, and
      fractions containing SDG are pooled, concentrated, and applied to a second column
      chromatography under the same conditions. Elution with water results in a better
      resolution of SDG [94.5% by high-performance liquid chromatography (HPLC)] than
      that with pure ethanol or 50% (v/v) aqueous ethanol. HPLC-photodiode array
      detection-mass spectrometry and NMR are applied to identify SDG and to determine
      the purity of the eluted fraction. This simplified purification scheme avoids
      toxic organic solvent used in the common silica gel separation process and, thus,
      increases the safety of the process.

PMID- 17504565
TI  - Identification of organic acids in bayer liquors by GC-MS: a comparison using
      butylation and methylation.
AB  - Two well known derivatization methods, butylation and methylation, are compared
      by gas chromatography (GC)-mass spectrometry (MS) to identify organic acids in
      Bayer liquors. These two derivatization methods should be combined together for
      the determination of the carboxylic acids. Twenty-four organic acids are
      identified by GC-MS and 13 organic acids are firstly found in Bayer liquors. The
      retention times and the carbon number of these seven n-dicarboxylic acids (C(4)
      C(10)) are fit into the linear relationship in Microsoft Excel.

PMID- 17504566
TI  - Triterpenoids from swallow roots--a convenient HPLC method for separation.
AB  - A convenient semi-preparative high-performance liquid chromatography (HPLC)
      method for separating a mixture of triterpenoids (alpha-amyrin, beta-amyrin, and
      lupeol) and their corresponding acetates from the swallow roots (Decalepis
      hamiltonii Wight and Arn), which are known to have potential bioactive
      properties, is described. The swallow roots are found to be one of the richest
      natural sources for these compounds. The hexane extract of the dried spent root
      on column chromatography yields mixtures (i.e., triterpenoids and their acetates)
      containing at least three compounds in each. These could not be further separated
      using the routine chromatographic techniques, such as classical column
      chromatography and preparative thin-layer chromatography using various solvent
      systems. Therefore, the optimal conditions are determined on reversed-phase HPLC
      for their separation and are characterized using spectral data, particularly by
      nuclear magnetic resonance with physical and chemical properties.

PMID- 17504567
TI  - Quantitation of glucosamine from shrimp waste using HPLC.
AB  - This work presents a high-performance liquid chromatography (HPLC) method for the
      quantitation of glucosamine in chitin. The method includes an acid hydrolysis of
      chitin. The chromatographic separation is achieved using a Hypersil ODS 5-microm
      column (250 x 4.6 mm) at 38 degrees C, with precolumn derivatization with 9
      fluorenylmethyl-chloroformate and UV detection (lambda = 264 nm). The mobile
      phase is a mixture of mobile phase A [30 mM ammonium phosphate (pH 6.5) in 15:85
      methanol-water (v/v)], mobile phase B [15:85 methanol-water (v/v)], and mobile
      phase C [90:10 acetonitrile-water (v/v)], with a flow rate of 1.2 mL/min. The
      HPLC method proposed showed adequate repeatability (relative standard deviation,
      5.8%), accuracy (92.7% recovery), and sensitivity, with a detection limit of 2
      microg/mL. The method is successfully applied to the quantitation of glucosamine
      for the determination of the purity of chitin from shrimp waste.

PMID- 17504568
TI  - Compositional monosaccharide analysis of transgenic corn glycoproteins by HPLC
      with fluorescence detection and LC-MS with sonic spray ionization.
AB  - Transgenic corn offers an attractive, cost-effective means for the large-scale
      production of engineered glycoproteins suitable for pharmaceutical purposes. A
      glycoprotein expressed in transgenic corn theoretically should not contain
      glycans because glycosylation sites have been genetically altered. A sensitive
      and reliable analytical method is developed to investigate this particular
      protein for the presence of glycans by monitoring the monosaccharide composition.
      Identification and quantitation of low-level monosaccharides in the glycoprotein
      hydrolyzate are accomplished by derivatization prior to high-performance liquid
      chromatography (HPLC)-fluorescence and liquid chromatography (LC)-sonic spray
      ionization (SSI)-mass spectrometry (MS) analyses. LC-SSI-MS is used to confirm
      the results from HPLC-fluorescence analysis and to positively identify the
      compositional monosaccharides. Glucosamine, glucose, mannose, arabinose, xylose,
      and sialic acid are found in the transgenic corn derived glycoprotein at less
      than one moiety per protein, which indicates heterogeneity of the particular
      glycoprotein. In addition to the compositional analysis of low-level
      monosaccharides in glycoprotein by HPLC-fluorescence, the utility of SSI for the
      LC-MS analysis of derivatized monosaccharides is demonstrated in this paper.

PMID- 17504569
TI  - Retention of histidine-containing peptides on a nickel affinity column.
AB  - The retention of histidine-containing peptides in immobilized metal-affinity
      chromatography is studied using several hundred modeled peptides. Retention is
      driven primarily by the number of histidine residues; however, the amino acid
      composition in the immediate vicinity plays a significant role. Specifically, the
      arginine and tryptophan content has to be taken into consideration. During the
      course of this study, an alternative tag that can be used similarly to a
      polyhistidine tag is discovered.

PMID- 17504570
TI  - A high-performance liquid chromatography with UV-vis detection method for the
      determination of Brazilein in plant extract.
AB  - A previously established mobile phase composition for a high-performance liquid
      chromatography (HPLC)-electrochemical detection (ED) method for the determination
      of Brazilein is further examined by HPLC-UV. Each component in the mobile phase
      is evaluated by the HPLC-UV system, and a convenient HPLC-UV method for the
      determination of Brazilein is developed. The mobile phase of this HPLC-UV method
      consists of sodium dihydrogen phosphate (NaH(2)PO(4)). The detection limit of
      Brazilein (signal-to-noise = 3) is 1 ng, and the calibration graph of Brazilein
      ranges from 1-120 ng per 20-microL injection. The validity of the proposed HPLC
      UV method is demonstrated by the analysis of Brazilein in real plant samples. The
      differences between the HPLC-ED method and the proposed HPLC-UV method are given.

PMID- 17504571
TI  - Simultaneous determination of seven flavonoids in Potentilla multifida by HPLC.
AB  - A reversed-phase high-performance liquid chromatographic method is described for
      the simultaneous determination of seven flavonoids in Potentilla multifida:
      hyperin, quercetin-3-O-beta-D-glucopyranoside, luteolin-7-O-beta-D-glucuronide,
      apigenin-7-O-beta-D-glucuronide, quercetin, tribuloside, and apigenin. The method
      involves the use of a Hypersil octadecylsilyl silica (ODS) analytical column
      (125A, 5 microm, 4.6 x 250 mm) at 25 degrees C with the mixture of acetonitrile
      and aqueous H(3)PO(4) as the mobile phase and detection at 254 nm. The recovery
      of the method is 95.4-104.8%, and linearity (r > 0.9998) is obtained for all the
      flavonoids. The results indicate that the flavonoid content of P. multifida
      varied significantly from locality to locality.

PMID- 17504572
TI  - Development and validation of an ion-pairing RP-HPLC method for the estimation of
      gatifloxacin in bulk and formulations.
AB  - A new, simple, and sensitive ion-pair reverse-phase liquid chromatographic method
      is developed and validated for the estimation of 1-cyclopropyl-6-fluoro-8-methoxy
      7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
      (gatifloxacin) in bulk and formulations using a UV detector under isocratic
      conditions. The selected mobile phase consists of the aqueous phase (a 25 mM
      citrate buffer comprising of 10mM cationic and anionic pairing agents, pH
      adjusted to 3.5) and acetonitrile (52:48%, v/v). The selected wavelength is 292
      nm. Retention time of gatifloxacin is 5.2 min. The linearity range is found to be
      50 to 1000 ng/mL (the regression equation is area = 105.5 x concentration in
      ng/mL--695.8), and the regression coefficient is 0.9996. Validation results
      demonstrate accuracy, precision, and reproducibility (relative standard deviation
      < 3%) of the method. The detection and quantitation limits are found to be 6.50
      and 17.38 ng/mL, respectively. The method is successfully used for the estimation
      of gatifloxacin in a variety of dosage forms, and the results are in good
      agreement with the label claims.

PMID- 17504573
TI  - Analysing the doctor-patient-computer relationship: the use of video data.
AB  - This paper examines the utility of using digital video data in observational
      studies involving doctors' and patients' use of computers in the consultation.
      Previous observational studies have used either direct observations or analogue
      videotapes. We describe a method currently in use in a study examining how
      doctors, patients and computers interact in the consultation. The study is set in
      general practice as this is the most clinically computerised section of the
      Australian healthcare system. Computers are now used for clinical functions in
      90% of doctors' surgeries. With this rapid rise of computerisation, concerns have
      been expressed as to how the computer will affect the doctor-patient
      relationship. To assess how doctors, patients and computers interact, we have
      chosen an observational technique, namely to make digital videotapes of actual
      consultations. This analysis is based on a theoretical framework derived from
      dramaturgical analysis. Data are gathered from general practitioners who are high
      level users of computers, as defined by their use of progress notes, as well as
      prescribing and test ordering. The subsequent digital data is then transferred
      onto computer and analysed according to our conceptual framework, making use of
      video-tagging software.

PMID- 17504574
TI  - XML-based clinical data standardisation in the National Health Service Scotland.
AB  - The objective of this paper is to clarify the role that socio-economic factors
      played in shaping the development of XML-based clinical data standards in the
      National Health Service in Scotland from 2000 to 2004. The paper discusses the
      NHS Scotland approach to clinical data standardisation, emphasising the actors
      involved, their choices during the standard development process and the factors
      that have shaped these choices. The case suggests that the NHS Scotland approach
      to clinical data standardisation is shaped by strong political pressures for fast
      development of an integrated electronic patient care system, economic pressures
      for high efficiency and cost reductions, and organisational requirements for
      strong clinical support. Such economic, political and organisational pressures
      explain the informal approach to standard development, the emphasis on fast
      system development and strong clinical involvement. At the same time, market
      factors explain the low commitment of the IT vendors, which might have otherwise
      put significant pressure on NHS Scotland to pursue a more formalised
      standardisation approach within an internationally recognised standard-setting
      body.

PMID- 17504576
TI  - Smoking status recording in GP electronic records: the unrealised potential.
AB  - OBJECTIVE: To investigate the recording of smoking status and factors associated
      with the recording of smoking status in general practitioner (GP) electronic
      medical records (EMRs) in New Zealand, and the suitability of this source as a
      prevalence measure. SETTING: General practices affiliated with an Auckland-based
      primary health organisation. POPULATION: Patients registered with 84/107 (78.5%)
      eligible GPs who had used EMRs for at least a year and had PREDICT-CVD, a web
      based cardiovascular disease risk assessment and management decision support
      program, integrated with their practice software. DESIGN: Audit of EMRs using
      data from an evaluation of PREDICT-CVD. MAIN OUTCOME MEASURES: The proportion of
      EMRs audited (Maori, non-Maori) with smoking status recorded and, among those
      with smoking status recorded, also Read-coded, and factors associated with
      greater recording of smoking status. RESULTS: Smoking status was recorded among
      49.6% of Maori and 38.3% of non-Maori prior to the installation of PREDICT-CVD.
      Among those with smoking status recorded, smoking status was also Read-coded
      among 49.8% of Maori and 62.3% of non-Maori. Factors associated with greater
      recording of smoking status were installation of PREDICT-CVD, male sex, Maori
      ethnicity, cardiovascular disease and diabetes. Age was also associated with the
      recording of smoking status. CONCLUSION: General practitioner electronic medical
      records in New Zealand are currently not a suitable source of smoking prevalence
      data, even if manually searched, as a large proportion of records did not have
      smoking status recorded. Such records are an even less suitable source of smoking
      prevalence if data extraction by remote querying (using Read codes) is relied
      upon. The potential to estimate the prevalence of smoking from GP records has not
      yet become a reality. Installation of electronic decision support systems, such
      as PREDICT-CVD, could improve the recording and Read-coding of smoking status,
      and thereby the availability and accessibility of these data.

PMID- 17504579
TI  - Biomedical Informatics: developing university, healthcare and industrial
      partnerships.

PMID- 17504578
TI  - President's report: December 2006.

PMID- 17504581
TI  - Honour your father and mother: ageism in medicine.

PMID- 17504583
TI  - How much monitoring?

PMID- 17504582
TI  - We need a chronic disease management model for depression in primary care.

PMID- 17504584
TI  - A qualitative study of lay beliefs about influenza immunisation in older people.
AB  - BACKGROUND: Although influenza immunisation is now recommended for all people
      aged 65 years and over in the UK, many people in that age group still remain
      unimmunised. AIM: To investigate lay beliefs about influenza and influenza
      vaccine in older people to identify appropriate ways of promoting vaccine uptake.
      DESIGN: Qualitative study using narrative interviews. SETTING: Urban and rural
      communities in South Wales. METHOD: Participants were 54 people aged 65 years and
      over who were interviewed in their own home. Of these, 11 were regularly
      immunised, 18 had consistently refused immunisation (refusers), 15 had defaulted
      (defaulters), five had never been offered immunisation, and five had recently
      been immunised for the first time. RESULTS: There was an overwhelming consensus
      among immunised and unimmunised individuals that they were not at risk from
      influenza. Even if they did catch influenza, they would not suffer from any
      serious consequences. Refusers and defaulters were more likely to believe that
      the influenza vaccine had serious side-effects, while the regularly immunised
      group were more likely to perceive the vaccine as effective. Multiple prompts
      from family, friends, or primary care staff were important triggers for receiving
      immunisation. CONCLUSION: Many older people did not feel vulnerable to influenza,
      regardless of their age, and this influenced their views on the need for
      immunisation. Both refusers and defaulters overstated adverse effects from
      influenza vaccine so this is a potential target for an intervention. Individual
      prompts, particularly from GPs, seemed to be the most significant motivators to
      attend for immunisation.

PMID- 17504585
TI  - Influenza vaccination in patients with asthma: why is the uptake so low?
AB  - BACKGROUND: Patients with asthma are particularly susceptible to serious
      complications from influenza. The Chief Medical Officer recommends annual
      influenza vaccination for adult patients with asthma. The uptake of influenza
      vaccination by patients with asthma is only 40% and, unlike other high-risk
      groups, has failed to increase in recent years. AIM: To investigate the
      contribution of sociodemographic factors, asthma morbidity, and health beliefs to
      influenza vaccination uptake in patients with asthma. DESIGN OF STUDY: Cross
      sectional questionnaire study. SETTING: Single urban British general practice,
      Exeter, UK. METHOD: A questionnaire survey was sent to adult patients with
      asthma. Participants were aged 16-65 years, were receiving beta(2) agonists and
      inhaled steroids, and had been invited for influenza vaccination in September
      2003. Data were examined using univariate analysis and logistic regression.
      RESULTS: A total of 136/204 (66.7%) patients responded to the survey. Influenza
      vaccination uptake in the study population was 40%. Younger patients were less
      likely to have undergone vaccination than older patients. There was no difference
      in vaccination uptake rates between groups of patients defined by other
      sociodemographic factors. Asthma morbidity was similar in vaccinated and non
      vaccinated groups of patients. Vaccinated individuals had a greater belief in the
      efficacy of the vaccination and medical advice regarding the vaccination, and
      felt more susceptible to influenza and its complications when compared with non
      vaccinated individuals. A fear of side-effects was associated with declining the
      invitation for vaccination. These health beliefs were the only independent
      predictors of uptake of influenza vaccination among this group of patients with
      asthma. CONCLUSION: Improving vaccination uptake in patients with asthma is
      unlikely unless individual health beliefs are taken into account.

PMID- 17504586
TI  - A randomised controlled trial to test the feasibility of a collaborative care
      model for the management of depression in older people.
AB  - BACKGROUND: Depression is the most common mental health disorder in people aged
      over 65 years. Late-life depression is associated with chronic illness and
      disability. AIM: To investigate the feasibility of a collaborative care model for
      depression in older people in a primary care setting. DESIGN OF STUDY: Randomised
      controlled trial with 16-weeks follow up. SETTING: A primary care trust in
      Manchester. METHOD: Participants were 105 people aged 60 years or older who
      scored 5 or more on the Geriatric Depression Scale; 53 were randomly allocated to
      an intervention group and 52 to a usual care group. The intervention group
      received care managed by a community psychiatric nurse who delivered an
      intervention comprising a facilitated self-help programme with close liaison with
      primary care professionals and old-age psychiatry according to a defined
      protocol. The usual care group received usual GP care. A nested qualitative study
      explored the views of the health professionals and patients regarding the
      acceptability and effectiveness of the intervention. RESULTS: The main outcome
      measure was recovery from depression. Patients in the intervention group were
      less likely to suffer from major depressive disorder at follow up compared with
      usual care (0.32, 95% confidence = interval = 0.11 to 0.93, P = 0.036). The
      qualitative component of the study demonstrated the acceptability of the
      intervention to patients. CONCLUSION: A model of collaborative care for older
      people with depression, used in a primary care setting with a facilitated self
      help intervention is more effective than usual GP care. This study demonstrates
      that the implementation of a collaborative care model is feasible in UK primary
      care and that the intervention is effective and acceptable to patients.

PMID- 17504587
TI  - Rectal and postmenopausal bleeding: consultation and referral of patients with
      and without severe mental health problems.
AB  - BACKGROUND: People with severe mental health problems receive less effective care
      for some physical conditions. There is concern that this could apply to rectal
      bleeding or postmenopausal bleeding. Published estimates of consultation rates
      and outcomes for these symptoms vary widely. AIM: To estimate rates of first-ever
      consultation for rectal bleeding and postmenopausal bleeding in general practice,
      together with subsequent referrals and outcomes. To identify inequalities for
      patients with severe mental health problems. DESIGN OF STUDY: Cohort study.
      SETTING: Primary care. METHOD: Patients with first-ever consultations for rectal
      or postmenopausal bleeding were identified among more than 3 million patients
      from 328 practices contributing routine data to the QRESEARCH database. Their
      records were followed for 2 years. RESULTS: There were 30 175 first consultations
      for rectal bleeding (2.6 per thousand patients per year at age 25-29 years,
      rising to 4.8 over age 85 years) and 10 142 for postmenopausal bleeding (highest
      at 7.4 per thousand per year aged 55-59 years). Overall, 2.2% of those with
      rectal bleeding and 1.7% of those with postmenopausal bleeding went on to have a
      relevant cancer diagnosis within 2 years. Cancer risk was strongly related to
      age, and was higher for males with rectal bleeding than females with rectal
      bleeding. Recorded referrals were at similar rates among patients with and
      without severe mental health problems. CONCLUSION: The rate of first
      consultations for rectal bleeding or postmenopausal bleeding is relatively low.
      Less than 2.5% overall have a relevant cancer diagnosis within 2 years. There is
      no evidence of inequality in referral for patients with severe mental health
      problems.

PMID- 17504588
TI  - Effect of the characteristics of family physicians on their utilisation of
      laboratory tests.
AB  - BACKGROUND: The use of laboratory tests by family physicians has increased in
      recent years. AIMS: To evaluate the relationship between family physicians'
      characteristics and the number and type of laboratory tests requested, taking
      into account chronic diseases. DESIGN OF STUDY: Retrospective, cross-sectional
      study. SETTING: One hundred and sixty-two physicians treating 230 123 patients in
      one district of a health management organisation in Israel. METHOD: Physicians'
      use of 16 common types of laboratory tests was assessed in relation to
      physicians' demographic, professional, and clinic characteristics. The
      utilisation rate over 1 year was divided into quintiles for each laboratory test,
      and each physician was given a global laboratory score (for each test the
      physician got a score from 1 (utilisation in the lower quintile) to 5 (higher
      quintile). The global score was the sum of scores of the individual tests.
      RESULTS: On logistic regression analysis, four background characteristics were
      associated with the global score for the utilisation of laboratory tests. The
      highest hazard ratios were for being a female doctor (3.2, 95% confidence
      interval [CI] = 1.5 to 6.5), working in an urban clinic (3.2, 95% CI = 1.1 to
      9.8), and having a greater workload than doctors in rural clinics (1.4, 95% CI =
      1.1 to 1.8). Being a graduate of a Western country or Israel had a negative
      association with the global score (0.4, 95% CI = 0.1 to 0.99). CONCLUSION: Female
      sex and working in a urban clinic were major factors in the use of laboratory
      tests in clinical practice. As more women enter the medical profession, an
      improved understanding of the sex differences in ordering medical tests is
      important.

PMID- 17504589
TI  - Assessing communication skills of clinical call handlers working at an out-of
      hours centre: development of the RICE rating scale.
AB  - BACKGROUND: Out-of-hours centres provide telephone support to patients with
      medical problems. In most of these centres specially-trained nurses handle
      incoming telephone calls. They assess patients' needs, the degree of urgency, and
      determine the level of care required. Assessment of the medical problem and the
      quality of 'care-by-phone' depend on the medical and communication skills of the
      call handlers. AIM: To develop a valid, reliable, and practical rating scale to
      evaluate the communication skills of call handlers working at an out-of-hours
      centre and to improve quality of communication. DESIGN OF STUDY: Qualitative
      study with focus groups followed by validation of the rating scale and
      measurement of reliability (internal consistency). SETTING: Out-of-hours centres
      in the Netherlands. METHOD: A focus group developed the rating scale. Experts
      with experience in training and evaluating communication skills of medical
      students and GPs commented on the scale to ensure content validity. The
      reliability of the rating scale was tested in a pilot in which ten specially
      trained assessors scored six telephone calls each. RESULTS: The scale, known as
      the RICE rating scale, has 17 items divided over four different phases of the
      telephone consultation: Reason for calling; Information gathering; Conclusion;
      and Evaluation (RICE). Content validity of the scale was assessed by two experts.
      Reliability of the scale tested in the pilot was 0.73 (Cronbach's alpha).
      CONCLUSION: Establishing a rating scale to assess the communication skills of
      call handlers which meets common scientific demands, such as content validity and
      reliability, proved successful. This instrument can be used to give feedback to
      call handlers.

PMID- 17504590
TI  - How do patients referred to neurologists for headache differ from those managed
      in primary care?
AB  - BACKGROUND: Headache is the neurological symptom most frequently presented to GPs
      and referred to neurologists, but little is known about how referred patients
      differ from patients managed by GPs. AIM: To describe and compare headache
      patients managed in primary care with those referred to neurologists. DESIGN OF
      STUDY: Prospective study. SETTING: Eighteen general practices in south-east
      England. METHOD: This study examined 488 eligible patients consulting GPs with
      primary headache over 7 weeks and 81 patients referred to neurologists over 1
      year. Headache disability was measured by the Migraine Disability Assessment
      Score, headache impact by the Headache Impact Test, emotional distress by the
      Hospital Anxiety and Depression Scale and illness perception was assessed using
      the Illness Perception Questionnaire. RESULTS: Participants were 303 patients who
      agreed to participate. Both groups reported severe disability and very severe
      impact on functioning. Referred patients consulted more frequently than those not
      referred in the 3 months before referral (P = 0.003). There was no significant
      difference between GP-managed and referred groups in mean headache disability,
      impact, anxiety, depression, or satisfaction with care. The referred group were
      more likely to link an increased number of symptoms to their headaches (P =
      0.01), to have stronger emotional representations of their headaches (P = 0.006),
      to worry more (P = 0.001), and were made anxious by their headache symptoms (P =
      0.044). CONCLUSION: Patients who consult for headache experience severe
      disability and impact, and up to a third report anxiety and/or depression.
      Referral is not related to clinical severity of headaches, but is associated with
      higher consultation frequency and patients' anxiety and concern about their
      headache symptoms.

PMID- 17504592
TI  - Which test is best for Helicobacter pylori? A cost-effectiveness model using
      decision analysis.
AB  - GPs face a potential dilemma in deciding which test to use for detection of
      Helicobacter pylori. For patients with dyspepsia, the National Institute for
      Health and Clinical Excellence (NICE) advises primary care practitioners to adopt
      a 'test and treat' policy before considering a referral for gastroscopy. There
      are many ways of testing: serology, urea breath test, and faecal antigen test.
      NICE does not advocate any preferred single test for detecting H. pylori. In the
      current study a multi-stakeholder 2-day workshop was established to agree and
      populate a cost-effectiveness decision analysis model. The aim was to analyse the
      three types of tests available for H. pylori and to determine which is the most
      practical and cost effective. Agreement on the costs and diagnostic values to be
      entered into the decision-analytic model was achieved. Results indicate that the
      faecal antigen test was the most effective in terms of true outcomes and cost.
      One thousand virtual patients were allocated to each of the three tests. Serology
      had 903, urea breath test had 961, and the faecal antigen test had 968 true
      positive outcomes. Data indicate that the faecal antigen test is the preferable
      strategy for diagnosis of H. pylori in primary care. This has implications for
      implementing new testing processes and for commissioning new diagnostic pathways
      for use in primary care.

PMID- 17504591
TI  - Utilisation of health care by women who have suffered abuse: a descriptive study
      on medical records in family practice.
AB  - BACKGROUND: Female patients, abused by their partner, are heavy users of medical
      services. To date, valid indicators of partner abuse of women are lacking. AIM:
      To outline the healthcare utilisation in family practice of women who have
      suffered abuse, and compare this to the average female population in family
      practice. DESIGN OF STUDY: As part of a primary study on the role of family
      doctors in recognising and managing partner abuse a retrospective study was
      performed. Anonymised data from the electronic medical records of women who have
      suffered abuse were collected over the period January 2001-July 2004. These data
      were compared to those from the average female population of the Second Dutch
      National Survey in General Practice 2001 (DNSGP-2). SETTING: Family practices in
      Rotterdam and surrounding areas in 2004. METHOD: The numbers of consultations and
      prescriptions for pain medication, tranquillisers and antidepressants of women
      who have suffered abuse (n = 92) were compared to those of the female population
      of the DNSGP-2 (n = 210 071). The presented health problems and referrals of the
      studied group were examined. RESULTS: Pain, in all its manifestations, appeared
      to be the most frequently presented health problem. Compared to the female
      population of the DNSGP-2, in all age categories, women who have suffered abuse
      consult their family doctor almost twice as often and receive three to seven
      times more pain medication. CONCLUSION: A doubled consultation frequency, chronic
      pain and an excessively high number of prescriptions for pain medication are
      characteristics of healthcare utilisation of women have been abused in this
      study. These findings contribute to the development of the concept of the
      'symptomatic' female patient.

PMID- 17504593
TI  - Do women know that the risk of breast cancer increases with age?
AB  - It is important that women know that the risk of breast cancer increases with
      age. Women's knowledge of the increased risk will help to inform their health
      seeking behaviour. This study shows that over 50% of women wrongly believe that
      the risk does not vary with age. Only 1% are correctly informed, believing that
      the oldest group of women are at the greatest risk of breast cancer. Those
      working in primary care need to be aware of this lack of knowledge when patients
      consult.

PMID- 17504594
TI  - Self-harm and suicide associated with benzodiazepine usage.
AB  - Benzodiazepines are commonly prescribed in primary care for anxiety disorders and
      insomnia. However, they can cause dependence with withdrawal symptoms that are
      both physical and psychological. These complications are also more common with
      short-acting benzodiazepines such as lorazepam. This case report describes a
      previously stable 62-year-old male who inflicted serious stab wounds to himself,
      twice within a month, during changes in his benzodiazepine regime.

PMID- 17504595
TI  - Women in medicine.

PMID- 17504596
TI  - Survival statistics.

PMID- 17504597
TI  - Handshakes and spoof publications.

PMID- 17504598
TI  - Mental health workers.

PMID- 17504599
TI  - Short screening tools for depression.

PMID- 17504600
TI  - Embracing clinical supervision.

PMID- 17504601
TI  - Jury service.

PMID- 17504602
TI  - Medical situation in Iraq.

PMID- 17504603
TI  - Patient-centred diagnosis.

PMID- 17504607
TI  - A GP in London: 1939-1945.

PMID- 17504604
TI  - Popular health advice: entertainment or risk factor?

PMID- 17504609
TI  - Supermarket medicine?

PMID- 17504611
TI  - Aspirin express.

PMID- 17504612
TI  - Tips and tricks in performing a systematic review.

PMID- 17504614
TI  - [Pay attention to the international frontline of nutritional science, attach
      importance to and strengthen building up of pediatric procession for nutrition].

PMID- 17504615
TI  - [Zinc deficiency and infectious disease in childhood].

PMID- 17504616
TI  - [A randomized controlled clinical trial for treatment of children with primary
      nocturnal enuresis].
AB  - OBJECTIVE: Applying three treatment methods for enuresis in children with primary
      nocturnal enuresis (PNE) in a randomized controlled clinical trial (RCT) to
      compare the curative effects and characteristics of the three methods. METHODS:
      If the parents and children consented to accept the treatment for 4 months and to
      keep on follow-up, the children diagnosed as primary nocturnal enuresis in the
      department of developmental and behavioral pediatrics in Shanghai Children's
      Medical Center from April 2003 to August 2004 were randomized into three groups:
      52 children were in physio-psychological treatment group and were treated by
      utilizing the conditioning training role of alarm and other psychological and
      behavioral training programs; 46 children were in drug treatment group and were
      treated by taking DDAVP tablets orally; 40 children were in combined treatment
      group who were treated by applying the former two methods simultaneously. If the
      parents and children did not accept treatment, they were enrolled into the
      control group and were followed-up. Then, the curative effects of the four groups
      were compared statistically when the 4-month treatment was over and compared
      again 3 months later. RESULTS: Applying the physio-psychological treatment for 4
      months, the short-term cure rate of children with enuresis was 75.0%. Three
      months after the end of the treatment, the long-term cure rate was 71.2%. As for
      drug treatment group, the short-term cure rate of children with enuresis was
      47.8%, the long-term cure rate was 28.3%; As for combined treatment group, the
      short-term cure rate of children with enuresis was 85.0%, the long-term cure rate
      was 80.0%. The short-term and long-term curative effects of physio-psychological
      treatment group and combined treatment group were better than that of drug
      treatment group (P < 0.01). However, the short-term and long-term curative
      effects were not significantly different between physio-psychological treatment
      and combined treatment group (P > 0.05). Physio-psychological treatment exerts
      effects slowly, but showed sustained curative effects. While Drug treatment
      exerts effects rapidly, but the relapse rate was very high after discontinuation
      of the medication. CONCLUSIONS: Physio-psychological treatment and drug treatment
      are currently generally recognized the best ways to treat enuresis, both of them
      are suitable for Chinese enuresis children, both of them showed good curative
      effects. Physio-psychological treatment develops children's ability to control
      nocturnal micturition, its curative effects were better than that of the drug
      treatment whilst its relapse rate is lower as compared to drug treatment. So,
      physio-psychological treatment is more suitable for widespread use to treat PNE
      in China.

PMID- 17504617
TI  - [Family risk factors of overweight and obesity in preschool children].
AB  - OBJECTIVE: To explore family risk factors of overweight and obesity focusing on
      parental characteristics, feeding practice and lifestyle. METHODS: Five
      kindergartens were selected randomly from two of all the six urban districts in
      Beijing. The body height and weight of all the children in the 5 kindergartens
      were measured in light clothing and without shoes. Information on parental
      characteristics, dietary habits, lifestyle, and feeding practice was collected
      from 1173 families by parental self-report questionnaires in the 5 kindergartens.
      Overweight and obesity were defined according to sex- and age-specific body mass
      index (BMI) cut-points proposed by the International Obesity Task Force.
      Correlations and multivariate regression analysis was used to explore risk
      factors of child overweight and obesity. RESULTS: The prevalence of overweight
      and obesity was 6.9% and 4.1%, respectively, among the sample children.
      Significantly more overweight and obese children were from obese families (15.2%)
      than they were from non-obese families (7.5%). Significant associations could be
      observed between children and parents' characteristics for BMI, frequency of
      eating in restaurant, television-watching hours, and physical activity hours.
      Parental obesity, low maternal education level and television watching for > 2
      h/d were risk factors of child overweight and obesity after adjusting for sex,
      age, family income, and kindergarten. CONCLUSIONS: Child overweight and obesity
      were influenced by family environment. Strategies for prevention should include
      identified family risk factors.

PMID- 17504619
TI  - [Brief report of work of the Subspecialty Group of Endocrinologic, Hereditary and
      Metabolic Diseases, The Society of Pediatrics, Chinese Medical Association].

PMID- 17504618
TI  - [Development and psychometric properties of the Chinese version of Children's
      Sleep Habits Questionnaire].
AB  - OBJECTIVE: To develop the Chinese version of Children's Sleep Habits
      Questionnaire (CSHQ) by translating and retranslating the English version of CSHQ
      and to examine the reliability, content validity, construct validity of the
      Chinese version in a general population of school-age children. METHODS: During
      November and December 2005, a total of 20 457 school-age children from 55 primary
      schools of 9 cities were recruited through cluster-stratified selection, using
      geographic location, economic standard, and population density as criteria. A
      parent-administered questionnaire and the Chinese version of CSHQ were completed
      to quantify sociodemographic characteristics and to characterize sleep patterns
      and sleep disturbances, respectively. RESULTS: The internal consistency of
      overall questionnaire and the eight subscales of the Chinese version of CSHQ was
      good (Cronbach's alpha coefficient was 0.73 and ranged from 0.42 to 0.69,
      respectively). The consistency between mother and father was ICCs = 0.89 for
      overall questionnaire and ranged from ICCs = 0.83 to ICCs = 0.92 for subscales.
      The test-retest reliability was ICCs = 0.85 for overall questionnaire and range
      from ICCs = 0.60 to ICCs = 0.88 for subscales. Factor analysis revealed a three
      factor structure, which could represent bedtime behavior problems, sleep
      disturbance, sleep duration and daytime sleepiness, respectively, and the three
      factors could be used to explain 58.63% of the total variance. The factor loading
      was above 0.5 for the corresponding subscale. CONCLUSIONS: Reliability, content
      validity and construct validity of the Chinese version of CSHQ in a general
      population of school-age children are good. It appears to be a suitable
      instrument for measuring sleep patterns and screening for sleep problems in
      school-aged children.

PMID- 17504620
TI  - [Summary of the national symposium on childhood nutrition].

PMID- 17504621
TI  - [Extrauterine growth retardation and correlated factors in premature neonates].
AB  - OBJECTIVE: Poor growth is a common problem in premature neonates. No sufficient
      attention has been paid to the nutrition deficit and extrauterine growth
      retardation in premature neonates in China. The present study aimed to assess the
      incidences of intrauterine growth retardation (IUGR) and extrauterine growth
      retardation (EUGR) in premature neonates in Shanghai area and their correlated
      factors. METHODS: Data of the neonates discharged between January 1, 2003 and
      December 31, 2004 from 5 hospitals (Xinhua Hospital, Shanghai Children's Medical
      Center, Shanghai Children's Hospital, Pediatric Hospital Affiliated to Fudan
      University, and Shanghai International Peace Maternity and Child Health Hospital)
      were reviewed. The criteria of exclusion were cases who died or had a malformed
      appearance, the mother had endocrine or metabolic diseases. The criteria for
      enrollment were (1) gestational age < 37 weeks, (2) admitted less than 24 hours
      after birth and discharged from the same hospital, (3) duration of
      hospitalization was > or = 7 days. The growth values on discharge of each patient
      were compared to the expected values based on the intrauterine growth data and
      postmenstrual day on discharge. Growth retardation was defined as measured growth
      values (weight, head circumference) < or = 10th percentile of the values (growth
      expectation based on estimated postmenstrual age). In each specific group, the
      number of neonates with < or = 10(th) percentile for each growth parameter was
      counted and the percentages of patients who had values < or = 10(th) percentile
      on birth and discharge were calculated. The growth curves used for assessing
      birth weight and head circumference for different gestational age neonates were
      those published in 1986. All the data were analyzed using the SPSS statistical
      software package. The risk factors for extrauterine growth retardation on weight
      and head circumference were estimated with logistic regression model. RESULTS:
      The subjects included 1196 premature neonates in the five hospitals (734 boys and
      462 girls). The incidence of IUGR was 22.7% and 19.2% assessed by weight and head
      circumference, respectively. The incidence of EUGR was 49.7% and 23.1% assessed
      by weight and head circumference, respectively. Assessment of IUGR in accordance
      with the birth weight and head circumference in the five hospitals showed no
      significant correlation between IUGR and non-IUGR by birth weight (chi(2) =
      4.944) and head circumference (chi(2) = 0.017) respectively. Whereas the
      assessment of EUGR in accordance with weight and head circumference showed a
      significant correlation between EUGR and non-EUGR by weight on discharge (chi(2)
      = 28.109), but no significant correlation was found between EUGR and non-EUGR by
      head circumference on discharge (chi(2) = 0.275). In specific birth weight
      groups, the lower the weight, the higher the incidence of IUGR and EUGR by the
      weight and head circumference. The incidence of EUGR in VLBWI was 78.9% and 50.0%
      assessed by weight and head circumference, respectively. Assessed by weight,
      significant correlation was observed between EUGR and non-EUGR in birth weight (t
      = 18.674), hospitalization duration (Z = -8.790) and the median number of day for
      total using EN (Z = -4.650); but by the head circumference, significant
      correlation was observed in head circumference at birth (t = 9.555),
      hospitalization duration (Z = -3.930) and the median number of day for total
      using EN (Z = -3.004). The relationship between EUGR and some risk factors was
      analyzed with Logistic regression model. Assessed by the weight, the following 4
      factors were related to EUGR: sex (chi(2) = 10.351), gestation age at birth
      (chi(2) = 56.275), birth weight (chi(2) = 102.126) and different hospital (chi(2)
      = 4.773). Assessed by the head circumference, the following 2 factors were
      correlated: gestation age at birth (chi(2) = 10.322) and head circumference
      (chi(2) = 10.620). CONCLUSIONS: This study showed that the incidence of EUGR in
      premature neonates was significantly higher than the data reported in other
      countries. The incidence of EUGR increased with the decreased birth weight.
      Different nutritional support had influence on EUGR.

PMID- 17504622
TI  - [Peritoneal equilibration test and results analysis in children undergoing
      chronic peritoneal dialysis].
AB  - OBJECTIVE: To explore the characteristics of peritoneal transport in children
      undergoing chronic peritoneal dialysis (PD). METHODS: Peritoneal equilibration
      test (PET) was carried out 10 times in 6 children (aged from 2 to 14 years) who
      were maintained by continuous ambulatory peritoneal dialysis (CAPD), and the
      peritoneal solution transport rate was evaluated by the standards of Twardowski's
      and Pediatric Peritoneal Dialysis Study Consortium (PPDSC)'s criteria. RESULTS:
      In this study, the initial PET was performed at (38.7 +/- 15.6) days following
      initiation of PD, the 4-hours of peritoneal creatinine clearance (4 h-D/P) and
      glucose absorption (4 h-D/D(0)) was (0.85 +/- 0.24) and (0.34 +/- 0.19),
      respectively. According to the standards of Twardowski's and PPDSC criteria, the
      peritoneal transport categories were divided into high transport (H) (6/10), high
      average transport (HA) (1/10), low average (LA) (3/10) for peritoneal solution
      transport, and H (3/10), HA (4/10), LA (1/10), low transport (2/10) for glucose
      absorption. No low transport type of solution was used in the patients. The
      coincidence rate of peritoneal creatinine and glucose transport types were 100%
      and 90% between the Twardowski's and PPDSC criteria, respectively. The different
      changes of peritoneal transport type were found in two patients with continuous
      PET. The value of 4 h-D/P increased after peritonitis episodes. CONCLUSION: The
      results showed that the PET in 70% of CAPD children fell into high and high
      average transport categories elevated by PPDSC's and adult standards, no-sinusoid
      distribution. The peritoneal solute clearance was adequate in the children, but
      net water ultrafiltration was lower. Standard pediatric PET and its criteria are
      consistent with the adult criteria. The capability of peritoneal solute transport
      increased after peritonitis episodes.

PMID- 17504623
TI  - [Radiofrequency perforation and balloon valvuloplasty in infants with pulmonary
      atresia and intact ventricular septum].
AB  - OBJECTIVE: To investigate the efficacy and safety of percutaneous radiofrequency
      perforation and valvuloplasty in infants with pulmonary atresia with intact
      ventricular septum (PA/IVS). METHODS: Four infants (body weight 4 - 10 kg) aged
      11 months, 9 months, 12 days and 9 months old, respectively, were hospitalized
      for dyspnea and cyanosis. All patients had a continuous murmur in the left second
      intercostal space. Doppler echocardiogram showed membranous pulmonary atresia
      with intact ventricular septum. Right ventriculogram showed a tripartite right
      ventricle, vasiform infundibulum, and membranous pulmonary valve atresia without
      ventriculocoronary connections. Descending thoracic aortogram showed good-sized
      confluent pulmonary arteries being filled from a ductus arteriosus. All the
      patients were taken up for radiofrequency perforation followed by a balloon
      dilatation. A 6F Judkins right coronary guiding catheter was positioned in the
      right ventricular outflow tract and under the atretic pulmonary valve membrane.
      The radiofrequency perforation catheter along with coaxial injectable catheter
      was then passed through the right coronary guiding catheter, using it as the
      guide to the imperforate membrane. The proximal end of the radiofrequency
      perforation catheter was then connected to radiofrequency generator. After the
      cusps of pulmonary valve were perforated, the coaxial injectable catheter was
      moved into the main pulmonary artery. A tiny floppy-tipped coronary guidewire was
      then passed through the coaxial injectable catheter into the main pulmonary
      artery and directed through the patent ductus arteriosus into the descending
      thoracic aorta or directed into pulmonary arteriola. Thereafter, serial balloon
      dilation catheters were introduced across the pulmonary valve, and dilations were
      sequentially performed with increasing balloon diameters. The balloon was dilated
      until the concave of the balloons disappeared. The radiofrequency energy (5 to 8
      W) was delivered for 2 to 5 seconds once, but commonly twice, to perforate the
      valves. After a predilation with a 3 mm x 20 mm to 5 mm x 20 mm balloon at 6 - 14
      atm pressure, the valve was subsequently dilated with 10 mm x 30 mm to 14 mm x 30
      mm balloon once or twice. The duration of procedures was 120 to 150 min and
      exposure time was 25.4 to 43.9 min. RESULTS: The primary procedure was successful
      in all the infants except one who died early of cardiac perforation with
      tamponade. After a follow-up period ranging from 2 to 8 months (mean 4.3 m), the
      remaining 3 survivors achieved complete biventricular circulation. Two of them
      were awaiting occlusion of the patent ductus arteriosus and 1 needed right
      ventricular outflow tract reconstruction because of infundibular obstruction.
      CONCLUSION: PA/IVS consists of 0.7% to 3.1% of congenital heart defects. 85% of
      the untreated patients die within half a year. Surgical repair for the infants
      with PA/IVS is associated with a high mortality. In carefully selected patients
      with PA/IVS, radiofrequency perforation and balloon dilatation of the pulmonary
      valve is feasible and may represent a new alternative to surgery due to its low
      mortality and avoidance of cardiopulmonary bypass.

PMID- 17504624
TI  - [Changes of body weight and galanin in epileptic children treated with
      topiramate].
AB  - OBJECTIVE: Topiramate is a new broad-spectrum anti-epileptic drug. Decreased body
      weight and appetite are common side effects of topiramate. The side effect
      affects the growth and development in children greatly. Little is known about the
      mechanisms of topiramate-induced weight loss and decreased appetite in children
      with epilepsy in China and abroad. galanin is one of factors that affect
      appetite. It is a neuroendocrine peptide and play an important role in the
      control of appetite and body weight in the mechanism of hormone release. The
      purpose of this study was to explore the mechanism of topiramate-induced weight
      loss in children with epilepsy and the relation of weight loss with change of
      galanin, thereby to provide evidences for improvement of quality of life,
      compliance to treatment and reduce side effects of growth and development in
      children with epilepsy. METHODS: Totally 61 patients with especial epilepsy were
      enrolled into this study and the disease was defined by clinical manifestations
      and electroencephalography (EEG). Among them 32 cases had generalized seizures
      and 29 had local seizures. Sixteen normal children were enrolled as control
      group. The patients' age ranged from 0.5 to 14 (4.76 +/- 4.05) years and the
      patients were instructed to take 0.5 - 1 mg/kg of topiramate per day, with 0.5 -
      1 mg/kg every 3 - 5 d increased to maximum of 3 - 8 mg/kg per day. Patients
      continued receiving the doses for 4 months. All patients' serum galanin levels
      and body height and weight and hepatic function were detected before and after
      antiepileptic drugs treatment. The galanin was detected by using
      radioimmunoassay. RESULTS: After treatment with topiramate (61 cases) for 4
      months, plasma galanin [(22.01 +/- 8.12) pg/ml] declined as compared with
      baseline [(26.56 +/- 9.35) pg/ml, t = 2.85, P < 0.01] in children with epilepsy.
      Twenty-two of 61 patients lost weight, their plasma galanin concentration was
      significantly lower [(26.51 +/- 10.00) pg/ml vs. (20.45 +/- 8.09) pg/ml, t =
      2.91, P < 0.01], but there was no significant change in the weight-gained
      patients (39/61) and control group (n = 16). In children with epilepsy, the mean
      value of body weight decreased as compared with the pre-treatment values, but the
      difference was not significant; however, the body-mass index (BMI) was
      significantly lower than that obtained before treatment (t = 8.628, P < 0.01).
      Eighteen of 22 patients who lost weight had decreased appetite, but only five of
      39 patients who gained weight showed decreased appetite (chi(2) = 28.50, P <
      0.001). The mean value of plasma galanin declined after treatment in patients (23
      cases) with decreased appetite [(18.35 +/- 7.80) pg/ml vs. (27.28 +/- 6.90)
      pg/ml, t = 4.84, P < 0.001]; while plasma galanin did not change significantly
      after treatment in patients (38 cases) without decreased appetite [(24.23 +/-
      7.66) pg/ml vs. (26.12 +/- 5.49) pg/ml, t = 1.04, P > 0.05]. CONCLUSION:
      Topiramate treatment may lower the body weight and reduce appetite in part of
      children with epilepsy which may be mediated by the reduced plasma galanin level.

PMID- 17504626
TI  - [Clinical features and genotype-phenotype studies of 89 Chinese patients with X
      linked adrenoleukodystrophy].
AB  - OBJECTIVE: X-linked adrenoleukodystrophy (X-ALD) is the most common inherited
      disorder of peroxisomal metabolism which is characterized by demyelination of
      central nervous system, impaired adrenal cortex and abnormal accumulation of very
      long chain fatty acids in body fluid and tissues. In this study, the clinical
      features and the genotype-phenotype relationship were investigated so as to help
      early diagnosis. METHODS: Clinical data of 89 Chinese patients with X-ALD were
      analyzed and mutation spectrums in 53 of the patients were investigated by
      polymerase chain reaction and DNA sequencing. RESULTS: Of the 89 cases, 60
      (67.4%) had childhood cerebral ALD (CCALD, mean age of onset was 6.5 years, range
      2 - 10 years), 18 (20.2%) had adolescent cerebral ALD (ACALD, mean age of onset
      12.1 years, range 11 - 19 years), 7 (7.9%) had adrenomyeloneuropathy (AMN, mean
      age of onset 23 years, range 6 - 39.5 years), and two cases were asymptomatic and
      another 2 had simple Addison's disease only. CCALD was the most common and severe
      phenotype, visual impairment was the most common initial symptom in CCALD and
      ACALD patients. Twenty four cases (63%) in whom hydrocortisone and ACTH were
      measured showed adrenal insufficiency. Forty five different mutations were
      identified in 53 patients. Missense mutations were the most common. No hotspot
      mutation was found in these patients and 1415delAG, the most frequent mutation
      found worldwide seemed not to be the real "hotspot" in these Chinese patients.
      The same phenotype may be due to diverse genomic mutations. A single mutation may
      result in different phenotypes even within a family. CONCLUSION: The phenotype
      distribution, initial symptom and gene mutation spectrum of Chinese patients may
      not be completely consistent with those in other countries. The clinical
      phenotype of the disease had no definite relationship with the nature of gene
      mutations.

PMID- 17504627
TI  - [Roles of CD8+ CD28- T regulatory cells in acute infectious mononucleosis in
      children].
AB  - OBJECTIVE: To explore the role of CD(8)(+)CD(28)(-) T regulatory cells (Tr) in
      the immunological pathogenesis of acute infection with Epstein-Barr virus in
      children. METHODS: The present study enrolled 25 children with infectious
      mononucleosis (IM) and 25 age-matched healthy children. Flow cytometric analysis
      was performed to detect the percentage of CD(3)(+), CD(3)(+)CD(4)(+),
      CD(3)(+)CD(8)(+), CD(8)(+)CD(28)(+) by determining the ratio of positive cells in
      lymphocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and real
      time PCR were used to analyze IL-6, IL-10, IFN-gamma expression in
      CD(8)(+)CD(28)(-) Tr cells and ILT-3, ILT-4 expression in monocytes/macrophages.
      RESULTS: The proportions of CD(8)(+)CD(28)(-)T cells in children with acute-phase
      IM was significantly higher than those in the controls (P < 0.01). The expression
      level of IL-6, IL-10, IFN-gamma, ILT-3, ILT-4 mRNA significantly increased
      compared to those of the controls (P < 0.01). CONCLUSION: The CD(28) expressed on
      CD(8)(+) T cells in vivo is gradually lost with age and CD(8)(+)CD(28)(-) cells
      increase up 50% to adult. EBV can directly infect B cells, trigger CD(8)(+) CTL
      response and destroy the target cells to cause serious immunopathological lesion.
      Therefore we speculate that the expansion of CD(8)(+)CD(28)(-) Tr cells in
      children with IM may be an adaptive immune response to avoid serious inflammation
      and autoimmune reactions.

PMID- 17504628
TI  - [Combined transplantation of neurotrophin-3 and neural stem cells in treatment of
      hypoxic-ischemic brain injury in rats].
AB  - OBJECTIVE: To evaluate the efficacy of combined transplantation of neurotrophin-3
      and neural stem cells in treatment of hypoxic-ischemic brain injury in rats, and
      study the possible mechanism. METHODS: Neural stem cells (NSCs) isolated from
      hippocampi of newborn wistar rats were cultured and identified. The hypoxic
      ischemic brain injury models established with 7-day-old wistar rats, and neural
      stem cells or others were transplantated into the ipsilateral ventricles 7 days
      later. The 7-day-old rats were randomized into 5 groups: normal group, model
      group, sham-transplantation group, NSCs transplantation group, and NT-3 combined
      with NSCs transplantation group. There were 12 rats per group. The functional
      test and immunohistochemistry were examined 4 weeks later. RESULTS: The neural
      stem cells from new-born rats' hippocampi were successfully cultured. It was
      found that they formed typical neurospheres in suspension, and the majorities of
      cells expressed nestin, which was the marker for neural stem cells. The rats from
      combined transplantation group performed significantly better in the ability to
      study and in memory and the limb function than the rats from NSCs transplantation
      group (P < 0.05). The rate of neural stem cells differentiating into neurons from
      combined transplantation group was higher, too (50% vs. 30%). CONCLUSION:
      Combined NT-3 and NSCs transplantation could improve the ability to study, memory
      and the limb function of rats after hypoxic-ischemic brain injury, and improve
      the rate of NSCs differentiating neurons. Combined NT-3 and NSCs transplantation
      had better effects on hypoxic-ischemic rats than transplantation of NSCs alone.

PMID- 17504629
TI  - [Clinical significance of serum clara cell secretory protein in children with
      asthma and asthmatoid bronchitis].

PMID- 17504630
TI  - [Levels of interleukin-23 in asthmatic children before and after
      glucocorticosteroid treatment].

PMID- 17504631
TI  - [Pulmonary function in infants with pneumonia caused by respiratory syncytial
      virus].

PMID- 17504632
TI  - [Effects of perinatal hypothyroidism on motor, learning and memory of young
      mice].

PMID- 17504633
TI  - [Guidelines for management of childhood community acquired pneumonia (for trial
      implementation) (II)].

PMID- 17504634
TI  - [Septal myocardial ablation for sick children with hypertrophic obstructive
      cardiomyopathy].

PMID- 17504635
TI  - [Risk factors and outcome of acute respiratory distress syndrome in pediatric
      patients with cancer].

PMID- 17504636
TI  - [Hallermann-Streiff syndrome: a case report].

PMID- 17504637
TI  - [Intracranial giant glioma in a neonate].

PMID- 17504638
TI  - [A case of congenital pleural effusion with Down syndrome].

PMID- 17504639
TI  - [Successful rescue of a case with 1, 2-dichlorethane and cyclohexanone
      intoxication].

PMID- 17504640
TI  - [Chronic arsenic poisoning in a child with idiopathic hypercalciuria].

PMID- 17504642
TI  - Potential clinical applications for spinal functional MRI.
AB  - Functional MRI (fMRI) of the spinal cord is a noninvasive technique for obtaining
      information regarding spinal cord neuronal function. This article provides a
      brief overview of recent developments in spinal cord fMRI and outlines potential
      applications, as well as the limitations that must be overcome, for using spinal
      fMRI in the clinic. This technique is currently used for research purposes, but
      significant potential exists for spinal fMRI to become an important clinical
      tool.

PMID- 17504643
TI  - Spontaneous pain and brain activity in neuropathic pain: functional MRI and
      pharmacologic functional MRI studies.
AB  - Functional brain imaging studies in chronic neuropathic pain patients have lagged
      far behind equivalent studies in acute pain. In the past few years, this trend
      has begun to shift. This article discusses the novel approach of studying brain
      activity for spontaneous pain and its modulation by pharmacologic manipulation.
      We argue that the approach provides a solid methodology for studying clinical
      (especially neuropathic) pain and patient populations, and moreover, that the
      latest results using this approach imply that distinct clinical chronic pain
      conditions seem to involve specific brain circuitry, which is also distinct from
      the brain activity commonly observed in acute pain.

PMID- 17504644
TI  - Imaging visceral pain.
AB  - The application of functional imaging to study visceral sensation has generated
      considerable interest regarding insight into the function of the brain-gut axis.
      Brain activation in normal control subjects during visceral sensation includes
      the perigenual cingulate cortex, which is involved in affective processing and
      has direct connections to autonomic centers. In contrast, somatic pain rarely
      activates the perigenual cingulate. This difference in brain activation is highly
      interpretable because visceral stimuli are experienced as more unpleasant than
      somatic stimuli. Clinical studies are suggestive of functional changes that may
      be a consequence or cause of conditions such as irritable bowel syndrome, but the
      findings are not consistent and are not as obviously interpretable as the
      differences observed when contrasting visceral and somatic stimulation. Although
      this is partly because brain imaging is still a relatively new technique, it also
      reflects weaknesses inherent to the understanding of chronic visceral pain as a
      biopsychosocial phenomenon. The biopsychosocial concept is very broad and rarely
      provides for precise predictions or mechanisms that can be directly tested using
      brain imaging. Future use of brain imaging to examine chronic visceral pain and
      other pain disorders will be more likely to succeed by describing clear
      theoretical and clinical endpoints.

PMID- 17504645
TI  - Imaging central pain syndromes.
AB  - Anatomic, functional, and neurochemical imaging studies have provided new
      investigative tools in the study of central pain. High-resolution imaging studies
      allow for precise determination of lesion location, whereas functional
      neuroimaging studies measure pathophysiologic consequences of injury to the
      central nervous system. Additionally, magnetic resonance spectroscopy evaluates
      lesion-induced neurochemical changes in specific brain regions that may be
      related to central pain. The small number of studies to date precludes definitive
      conclusions, but the recent findings provide information that either supports or
      refutes current hypotheses and can serve to generate new ideas.

PMID- 17504646
TI  - Imaging pain of fibromyalgia.
AB  - Brain imaging studies have provided objective evidence of abnormal central
      regulation of pain in fibromyalgia (FM). Resting brain blood flow studies have
      reported mixed findings for several brain regions, whereas decreased thalamic
      blood flow has been noted by several investigators. Studies examining the
      function of the nociceptive system in FM have reported augmented brain responses
      to both painful and non-painful stimuli that may be influenced by psychologic
      dispositions such as depressed mood and catastrophizing. Treatment approaches are
      beginning to demonstrate the potential for brain imaging to improve our
      understanding of pain-alleviating mechanisms. Data from other chronic conditions
      suggest that idiopathic pain may be maintained by similar central abnormalities
      as in FM, whereas chronic pain conditions with a known nociceptive source may not
      be. Future neuroimaging research in FM is clearly warranted and should continue
      to improve our understanding of factors involved in pain maintenance and symptom
      exacerbation.

PMID- 17504647
TI  - Phenotyping central nervous system circuitry in chronic pain using functional
      MRI: considerations and potential implications in the clinic.
AB  - Functional MRI (fMRI) has provided new insights into brain mechanisms in chronic
      pain. However, unlike acute pain measures in healthy volunteers, there are
      additional concerns relating to mapping brain circuits in these patients. These
      include the ability to measure evoked versus spontaneous pain, background
      conditions such as medications, or comorbid diseases such as depression, anxiety,
      or addiction. Nevertheless, our understanding of the centralization of pain with
      attendant changes in sensory, emotional, and autonomic function is being more
      clearly realized and has significant implications for defining the disease state
      and therapeutic interventions. It is possible that fMRI may become clinically
      useful.

PMID- 17504648
TI  - Update on pharmacotherapy guidelines for treatment of neuropathic pain.
AB  - Neuropathic pain encompasses a myriad of painful disease states that are often
      hard to treat, especially with one single medication. In the comprehensive
      treatment of neuropathic pain, the concept of complex polypharmacy is a rational
      approach, accompanied by physical and mental health therapies. Medications
      primarily used for neuropathic pain generally fall into the categories of
      anticonvulsants, antidepressants, opioids, and topical agents. Generally, most
      first-line medications used today show a response rate of approximately 30% to
      50% reduction in pain in up to 50% of patients treated. There is no "gold
      standard" in regard to one medication for neuropathic pain. Some new medications
      have emerged during the past few years that help to augment the armamentarium of
      medications used in neuropathic pain. This paper reviews the definition of
      neuropathic pain and introduces the reader to the evidence-based literature on
      these new medications available for the treatment of neuropathic pain.

PMID- 17504650
TI  - Preventative treatment of menstrual migraine.
AB  - More than 20 million US women suffer with migraine, two thirds of whom experience
      menstrually related migraine. Estrogen plays an important role in triggering
      migraine, and given the numerous hormonal fluctuations throughout a woman's
      lifetime, there are many opportunities for a hormonal impact. Accurate diagnosis
      is key to initiating effective treatment, and when acute therapy fails, the
      unique predictability of menstrual migraine lends itself to preventative
      treatment.

PMID- 17504649
TI  - Migraine-related vertigo: diagnosis and treatment.
AB  - A comprehensive review of the neurotologic manifestations of migraine is
      presented, focusing on the most recent publications regarding the epidemiology,
      clinical presentation, pathophysiology, diagnosis, and management of migraine
      related vertigo (MV). A strong association exists between vertigo and migraine,
      with MV being the most common cause of spontaneous (nonpositional) episodic
      vertigo. Symptoms can be quite variable among patients and within individual
      patients over time, creating a diagnostic challenge. MV generally presents with
      attacks of spontaneous or positional vertigo lasting seconds to days with
      associated migrainous symptoms. Operational diagnostic criteria have been
      proposed but are not included in the most recent International Headache Society
      classification of migraine. Better elucidation of the neurologic linkages between
      the central vestibular pathways and migraine-related pathways and the discovery
      of ion channel defects underlying some causes of familial migraine, ataxia, and
      vertigo have furthered the understanding of MV pathophysiology. Treatment of MV
      currently parallels that of migraine headache, as proper studies of optimal MV
      management are just beginning.

PMID- 17504651
TI  - Greater occipital nerve block for migraine and other headaches: is it useful?
AB  - Peripheral nerve blocks have long been used in headache treatment. The most
      widely used procedure for this purpose has been greater occipital nerve (GON)
      block. The rationale for using GON block in headache treatment comes from
      evidence for convergence of sensory input to trigeminal nucleus caudalis neurons
      from both cervical and trigeminal fibers. Although there is no standardized
      procedure for GON blockade, the nerve is usually infiltrated with a local
      anesthetic (lidocaine, bupivacaine, or both). A corticosteroid is sometimes
      added. Several studies suggested efficacy of GON block in the treatment of
      migraine, cluster headache, and chronic daily headache. However, few were
      controlled and blinded. Despite a favorable clinical experience, little evidence
      exists for the efficacy of GON block in migraine treatment. Controlled studies
      are needed to better assess the role of GON block in the treatment of migraine
      and other headaches.

PMID- 17504652
TI  - Patent foramen ovale and migraine.
AB  - Results from several observational studies indicate an association between
      migraine and patent foramen ovale (PFO). Several biological mechanisms have been
      proposed to explain this link, including shared genetic inheritance. However,
      there is currently insufficient evidence to support a causal link between PFO and
      migraine. Although the results of uncontrolled observational studies suggest the
      PFO closure may have a beneficial effect on migraine frequency, a large
      randomized trial failed to support such a conclusion. Until there is more
      evidence from ongoing large controlled trials, PFO closure should not be
      performed in clinical practice for the prophylaxis of migraine.

PMID- 17504653
TI  - Controlled trials in pediatric migraine: crossover versus parallel group.
AB  - Studies on the treatment of migraine in children and adolescents are rare and
      difficult to design. In particular, the high placebo response makes it difficult
      to show efficacy of a verum drug. When analyzing all published trials in the
      acute drug treatment of migraine in children, crossover trials show lower placebo
      rates and higher therapeutic gain, compared with parallel group trials. This
      should be considered in the future design of acute drug trials in childhood
      migraine.

PMID- 17504654
TI  - Oral allergy syndrome.

PMID- 17504655
TI  - Changing paradigms in the immunological science of allergy.
AB  - The nonallergic roles of mast cells in infections and immune tolerance recently
      have been elucidated more fully at mechanistic levels. Mast cells that have been
      activated by contact with microbial surfaces secrete chemotactic mediators
      capable of attracting leukocytes through blood vessels permeabilized by other
      mediators. In the setting of allograft transplantation, regulatory CD4 T cells
      promote tolerance both by direct immunosuppressive effects and by releasing
      interleukin (IL)-9 that attracts and stimulates differentiation of mast cells
      with the capacity to induce local tolerance. For the first time in over 20 years,
      two new subclasses of CD4 T cells have been identified that have major immune
      functions. The first are T-helper interleukin-17 (T(H)17) cells, which mediate
      acute and chronic inflammation in recurring exacerbations of autoimmune diseases,
      and the second are sets of adaptive regulatory T cells, which control CD4
      effector T cells and other immune effector cells by secreting transforming growth
      factor-beta or IL-10.

PMID- 17504656
TI  - Susceptibility to asthma and eczema from mucosal and epidermal expression of
      distinctive genes.
AB  - The past several years have seen an increase in the rate at which genes that are
      associated with allergic asthma and eczema are discovered. This review -examines
      genetic association, gene expression, and functional studies that have identified
      genes that are expressed in the epithelial cells of the skin and lung and are
      involved in the pathogenesis of allergic asthma and eczema. This includes the
      genes encoding thymic stromal lympho-poietin (TSLP) and suppressor of cytokine
      signaling (SOCS3) that are involved in the activation of T-helper 2 cells, the
      microbial pattern recognition receptors nucleotide-binding oligomerization domain
      (NOD) genes (CARD4 and CARD15), Toll-like receptors (TLR2 and TLR4), and
      filaggrin, a protein required for effective barrier defense of the skin.
      Therefore, the development of allergic disease involves both the adaptive and
      innate immune systems, and the expression of these genes in the skin and lungs
      suggests a link to environmental -triggers at body surfaces.

PMID- 17504657
TI  - Eosinophils and asthma.
AB  - Recruitment and activation of eosinophils into the airways of asthma patients is
      suggested to be a contributing causative agent in the histopathologies and lung
      dysfunction that are characteristic of asthma. Recent studies in mouse models of
      asthma and in human patients implicate eosinophils in immune regulation and
      remodeling in the lung in addition to their hypothesized role as destructive
      agents. Specifically, eosinophils not only participate in release of granule
      proteins, lipid mediators, reactive oxygen species, cytokines, and growth factors
      but also function through complex cell-cell interactions to elicit chronic T
      helper 2 inflammation in the lung. This review highlights the roles of
      eosinophils in asthma.

PMID- 17504658
TI  - Etiology of exercise-induced asthma: physical stress-induced transcription.
AB  - Exercise-induced asthma (EIA) occurs with a high prevalence in both asthmatic and
      nonasthmatic individuals. Although understanding of the functional genomics
      (proteomics) in sports medicine remains limited, this review focuses on
      immunologic changes as reflected in transcriptional regulation in respect to EIA.
      Studies demonstrated that leukotrienes play a significant role in EIA. Exercise
      increases the distribution of leukotrienes and influences the leukotriene
      transcription pathway; it could be shown that the genes ALOX5 and ALOX5AP
      encoding for 5-lipooxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP)
      as well as activators for 5-LO, p38 -mitogen-activated protein kinase (MAPK), and
      others, are enhanced after exercise in healthy subjects. Possibly EIA is
      triggered via leukotriene release if a predisposition or other conditions (eg,
      epithelial injury and repair) are present. Furthermore, exercise influences
      transcription factors such as nuclear factor-kappa B (NF-jB), activator protein-1
      (AP1), cytokines, and chemokines and promotes cellular responses linked to EIA,
      which are possibly able to modify further the incidence or the severity of EIA.

PMID- 17504659
TI  - Allergic reactions to nonsteroidal anti-inflammatory drugs: is newer better?
AB  - In clinical practice, physicians may find it difficult to recognize the
      differences between allergic and pseudo-allergic reactions to nonsteroidal anti
      inflammatory drugs (NSAIDs) and to manage each type of reaction. This paper
      reviews all the information presently available in order to clarify main problems
      related to NSAID reactions and to highlight key strategies to handle these
      reactions.

PMID- 17504660
TI  - Sulfonamide allergy and cross-reactivity.
AB  - Concerns about cross-allergenicity between sulfonamide antibiotics and
      nonantibiotic sulfonamide-containing drugs continue to complicate
      pharmacotherapy. Several elegant investigations have demonstrated unequivocal
      lack of interaction between the sulfonamide group and either cellular or humoral
      immunity. The immunologic determinant of type I immunologic responses to
      sulfonamide antibiotics is the N1 heterocyclic ring, and nonantibiotic
      sulfonamides lack this structural feature. Many non-type I hypersensitivity
      responses to sulfonamide antibiotics are attributable to reactive metabolites
      that cause either direct cytotoxicity or humoral or cellular responses.
      Metabolite formation is stereospecific to the N4 amino nitrogen of the
      sulfonamide antibiotics, a structure not found on any nonantibiotic sulfonamide
      drugs. Cellular immune responses to sulfonamide antibiotics are responsible for
      many non-immunoglobulin E-mediated dermatologic reactions; however, the
      stereospecificity of T-cell response renders cross-reactivity between sulfonamide
      antibiotics and nonantibiotics highly unlikely. Apparent cross-reactivity
      responses to sulfonamide-containing drugs likely represent multiple concurrent,
      rather than linked, drug hypersensitivities.

PMID- 17504661
TI  - Immunology of anaphylaxis: lessons from murine models.
AB  - The use of animal models is increasing, and mice are suitable animals to use in
      exploring systemic anaphylaxis based on the similarity between human and mouse
      immune systems. Two anaphylaxis pathways have been characterized in mice, which
      may help in understanding some of the discrepancies found in humans. In addition,
      cytokine studies are raising new concepts that may put together some of the
      puzzling mechanisms described in this disease. Finally, the study of the
      mechanisms that parasitic infections use to evade the human immune system and the
      scene in which a parasite induces clinical anaphylaxis are opening new insights
      in the immunology pathways and new strategies to fight against this exclusive
      disease.

PMID- 17504662
TI  - Modulation of anaphylaxis by helminth-derived products in animal models.
AB  - Helminths have a profound immunomodulatory effect upon the inductive and effector
      phases of inflammatory responses, including allergy. Several animal models of
      anaphylaxis have been established to investigate the mechanisms by which helminth
      infections or helminth-derived products interfere with the onset of allergic
      reactions. The focus of our studies was the immunosuppression induced by the
      intestinal roundworm Ascaris suum in the production of anaphylactic antibodies
      and the development of lung eosinophilic inflammation and hyperreactivity to its
      own allergens and to unrelated antigens. Thus, we identified a single protein
      affinity purified from the A. suum body extract, named PAS-1, which maintains all
      its immunosuppressive properties and promotes a significant increase in
      interleukin-10 production, an essential cytokine for the effectiveness of the
      suppressive mechanism. In addition, PAS-1 primes for regulatory T cells, which
      also mediate this mechanism. Therefore, this helminth molecule may be a promising
      target for therapeutic applications in allergic disorders.

PMID- 17504665
TI  - [Diabetes mellitus in hypertensive population attended in Primary Care in Spain.
      Blood pressure and lipid control rates].
AB  - OBJECTIVES AND METHODS: The aim of this study was to determine the blood pressure
      and LDL-cholesterol (LDL-c) control rates of hypertensive patients with diabetes
      mellitus attended in primary care setting in Spain, and to compare the data with
      those of the hypertensive population without diabetes. For this purpose, we
      analyzed the subset of diabetic patients of those included in the PRESCOT study
      (a cross-sectional survey of hypertensive subjects > 18 years attended in primary
      care). 12,954 patients (49.9% females; 62.1 +/- 10.7 years) were included in the
      PRESCOT study. Good controls were considered blood pressure < 130/80 mmHg
      (according to European Society of Hypertension-European Society of Cardiology
      [ESH-ESC] guidelines) and LDL-c < 100 mg/dl (National Cholesterol Education
      Program-Adult Treatment Panel III [NCEP-ATP III]). RESULTS: Overall, 3868 (29.9%)
      of PRESCOT patients were diabetics (mean age 64.2 +/- 9.8 years; 47.5% males).
      Almost all the diabetic patients (98.5%) were taking some drug besides the
      antidiabetic treatment and 84.9% were taking at least 2 drugs. Although diabetic
      patients were treated with more antihypertensive medication than those without
      diabetes (48.75% vs 40.85% were on > 2 drugs, p < 0.001), blood pressure control
      was much lower in diabetics (6.3% vs 32.7%, p < 0.0001). In the same way, LDL-c
      control was also lower in these patients (12.0% vs 31.9%, p < 0.0001). Only 1.0%
      of diabetic hypertensives were well controlled for both risk factors (vs 11.9% of
      non-diabetics, p < 0.0001). Predictors of bad blood pressure control were
      sedentarism and presence of associated clinical conditions, and for lipid control
      the younger age, female gender, overweight, alcoholism and non-use of lipid
      lowering agents. CONCLUSIONS: The presence of diabetes in hypertensive population
      attended in Spanish primary health care is frequent. One out of every three
      hypertensives who attend the outpatient clinic daily is diabetic. Even though
      more drugs are prescribed in these patients, blood pressure and LDL-c control
      rates are significantly lower than in patients without diabetes. In the daily
      practice of primary care setting, almost no diabetic hypertensive subject is well
      controlled for blood pressure and LDL-c.

PMID- 17504663
TI  - Are exhaled breath condensates useful in monitoring asthma?
AB  - Exhaled breath condensate (EBC) has emerged as a novel noninvasive technique for
      assessment of airway inflammation, and it also provides useful information on the
      airway lining fluid composition. Examples of markers that can be identified in
      the EBC of patients with asthma include pH, eicosanoids, nitrogen oxides and
      related products, markers of oxidative stress, certain cytokines, chemokines, and
      growth factors. There is some evidence that certain markers in EBC differ between
      patients with asthma and controls, and some markers may correlate with asthma
      severity and lung function, but there are many methodologic pitfalls with EBC
      assessment that limit its clinical applicability at present. More studies are
      needed before this technique can be recommended for clinical use.

PMID- 17504664
TI  - What is the role of virus vaccination in patients with asthma?
AB  - It is estimated that viruses play a role in 30% to 80% of asthma exacerbations.
      Thus, virus vaccination in patients with asthma could play an important role in
      preventing asthma exacerbations and other complications. Influenza is the only
      agent for which a routine vaccine is currently available. This article discusses
      whether influenza vaccination in patients with asthma, based on the available
      evidence, is justified. Cost-effectiveness of (influenza) vaccination for
      patients with asthma is questionable. For the other major viruses involved, the
      present state of affairs is described. Although progress is being made, a vaccine
      may be available in the near future only for respiratory syncytial virus (RSV).
      Meanwhile, clinicians and patients should aim for an optimal treatment with the
      currently available asthma medication.

PMID- 17504666
TI  - [Prevalence of peripheral artery disease evaluated by ankle brachial index in
      patients with metabolic syndrome. MERITO I study].
AB  - INTRODUCTION: Patients with Metabolic Syndrome have high cardiovascular morbidity
      and mortality rate above that expected when using accepted scales for risk
      stratification. Ankle brachial index (ABI) is an available, straightforward and
      reproducible method for the detection of peripheral vascular disease and for
      improving risk stratification in this population. Our study aimed to evaluate the
      prevalence of low ABI in patients with metabolic syndrome older than 50 years and
      to study the risk factors associated with its development. PATIENTS AND METHODS:
      1519 subjects between 50 and 85 years, 935 of them with metabolic syndrome (Adult
      Treatment Panel III [ATP III] criteria), in primary prevention, without symptoms
      of intermittent claudication and who gave their consent to have an ABI
      measurement in internal medicine offices were included in the study.
      Cardiovascular risk factors were evaluated in all participants. An ABI < 0.9 was
      considered low. RESULTS: The prevalence of a low ABI in subjects with metabolic
      syndrome was 27.7 (95% CI: 24.8-30.5). Factors associated with low and a
      pathological ABI were age, higher serum creatinine levels and presence of
      proteinuria. After multivariate adjustment, only age (OR: 1.07; 95% CI: 1.04
      1.09) and active tobacco use (OR: 1.45; 95% CI: 1.10-1.92) continued to be
      significant. CONCLUSION: Prevalence of a low ABI is elevated in subjects with
      metabolic syndrome without known cardiovascular disease and related with age and
      active tobacco use.

PMID- 17504667
TI  - [Health problems and social vulnerability in immigrants admitted for an
      infectious disease: a case-control study].
AB  - BACKGROUND: Health resources needed by immigrants have increased steadily in the
      last few years. Studying health problems and social vulnerability in immigrants
      would help to improve the health care quality. PATIENTS AND METHODS: A case
      control study performed in the Hospital Clinic of Barcelona. Immigrant patients
      admitted with infectious diseases from October 2002 to September 2003 were
      included. Controls were paired by age, gender and HIV infection. Clinical
      (emergency room attendance, days and number of admission to hospital, amount of
      clinical procedures and drugs used during the admission, etiological and
      microbiological diagnosis and post-admission control) and social vulnerability
      variables (social worker consultation, health care card, relatives or friends
      caregiver, drug use, language barrier and discharge document of the nurse) were
      analyzed. RESULTS: One hundred and two patients (51 cases and 51 controls, all of
      them males) were studied. A total of 56% were HIV-1 infected in both groups. The
      number of diagnostic or therapeutic procedures was higher in the immigrant group
      (p = 0.02), a lower proportion of patients had a final etiologic diagnosis (82%
      vs 98%, p = 0.021) and the number of post-discharge controls was lower (55% vs
      77%, p = 0.04). Immigrants had a higher social vulnerability index than the
      Spanish population and 35% could not speak Spanish, French or English. The number
      of immigrants with health care card was lower (63% vs 94%, p < 0,0001) and a
      higher number needed to be admitted to a social-health care center after
      discharge (16% vs 2%, p = 0.01). DISCUSSION: Social vulnerability influences the
      etiological diagnosis, the number of diagnostic and therapeutic procedures during
      the admission to the hospital and post-discharge control of immigrant population.

PMID- 17504668
TI  - [Acute exogenous lipoid pneumonia in "fire-eaters". Description of two cases].
AB  - Exogenous lipoid pneumonia is a rare disease that has traditionally been
      considered a chronic condition secondary to continued aspiration or inhalation of
      fatty substances. An acute form may sometimes appear after a single and massive
      aspiration of lipid material, being a characteristic accident of street artists
      or "fire-eaters" that may generate acute respiratory failure. In this paper, we
      present clinical and radiological signs and outcome of two cases of lipoid
      pneumonia in "fire-eaters". A few hours after exposure patients may develop
      fever, cough, chest pain, hemoptysis, pulmonary infiltrates or hypoxemia. While
      diagnosis of chronic forms may require invasive procedures, recent exposure to
      fatty substances is a clue for clinical diagnosis in acute forms. Acute forms
      usually have a good outcome but cases evolving to cavitary pneumonia have been
      described. Some patients can present with acute respiratory distress syndrome and
      death. Treatment is based on general supportive measures.

PMID- 17504669
TI  - [Clinical-biological analysis of thrombotic thrombocytopenic purpura in the
      General University Hospital of Alicante during 1983-2006].
AB  - OBJECTIVE: Our study aimed to evaluate the patients diagnosed of thrombotic
      thrombocytopenic purpura in our hospital during the last 23 years. METHODS: We
      have made a retrospective study of the clinical records of 25 patients diagnosed
      of TTP between 1983-2005, describing the clinical, epidemiological and laboratory
      data. RESULTS: Twenty-five cases were diagnosed. Mean age was 39 years, 64% women
      and 36% men, 44% had suffered headaches, 4% fever, 32% neurological focality, 12%
      renal disorders, 36% hemorrhagic disease and 16% thromboembolic disease. TTP
      etiology was: 72% idiopathic, 8% pregnancy, 4% Human Immunodeficiency Virus, 4%
      myasthenia gravis, 4% pulmonary neoplasm and 4% puerperium. Medium hemoglobin
      level was 9 g/dl, leucocytes 8700/mm3 and platelets 12000/mm3. Patients received
      a median of 5 plasmapheresis. Mean time to relapse was two months. Other
      treatments for TTP were aspirin (16%), cyclosporine (4%), vincristine (4%) and
      splenectomy (4%). CONCLUSIONS: PTT incidence in our region has increased in
      recent years, probably due to an increase in the immigrant population not
      included in the census, among the most relevant reasons. In our study, renal
      disorders and presence of fever were less frequently described than in other
      reports. There was no correlation between the number of plasmapheresis and
      likelihood of relapse. Most relapses were in idiopathic TTP.

PMID- 17504670
TI  - [Painful legs and moving toes syndrome].
AB  - Painful legs and moving toes syndrome is a rare medical picture characterized by
      involuntary movements of the toes or the whole foot and pain in lower limbs.
      However, this must be kept in mind due to its association with other diseases and
      its possibility of being the first symptom. Spinal cord and cauda equina
      diseases, neuropathies, radiculopathies, drugs and other systemic diseases are
      the main cause of this syndrome although many cases are still idiopathic. Its
      diagnosis is essentially clinical and its treatment is complex, including
      different combinations of drugs and invasive techniques, and generally with a bad
      response.

PMID- 17504671
TI  - [Utility and clinical relevance of the measurement of calculated glomerular
      filtration].
AB  - Isolated measurement of serum creatinine is insufficient for the adequate
      evaluation of renal function. The estimation of GF with formulae, known for its
      limitations, considerably increases the information obtained. It is recommendable
      that the clinical laboratories include an estimation of GF in their reports
      whenever a serum creatinine measurement is made.

PMID- 17504672
TI  - [75 year old man with middle lobe atelectasis].

PMID- 17504673
TI  - [Abdominal pain in an oncology patient].

PMID- 17504674
TI  - [Hepatic lesions and prolonged use of oral contraceptive].

PMID- 17504675
TI  - [52 year old woman with interstitial pulmonary pattern and severe mental
      retardation].

PMID- 17504676
TI  - [Esophageal-extradural fistula secondary to vertebral tuberculosis].

PMID- 17504677
TI  - [Profile towards organ donation of the Irish and Northern Irish residents in
      Southeast Spain].

PMID- 17504678
TI  - [Severe hypogammaglobulinemia in patients with autoimmune hemolytic anemia].

PMID- 17504679
TI  - [Oral anticoagulation in nonagenarians].

PMID- 17504680
TI  - [Antisynthetase syndrome with good response to mycophenolate mofetil].

PMID- 17504681
TI  - Short-course regimens for latent tuberculosis: what is ready for prime time?

PMID- 17504682
TI  - [Short-course isoniazid and rifampin compared with isoniazid for latent
      tuberculosis infection: a randomized clinical trial].
AB  - INTRODUCTION: The aim of this study was to compare the adherence to, and side
      effects of a 3-month short-course treatment for latent tuberculosis infection as
      compared to the standard 6-month course. METHODS: Prospective, comparative,
      randomized, open trial including patients with a positive tuberculin skin test
      and appropriate criteria for treatment in accordance with the CDC guidelines, and
      excluding patients with HIV infection. Group I (6H) was assigned to isoniazid 300
      mg per day for 6 months and Group II (3HR) was assigned to isoniazid 300 mg per
      day plus rifampin 600 mg per day for 3 months. The patients were followed up for
      five years. RESULTS: A total of 105 patients were included, among which 9 refused
      treatment; 45 patients were placed in Group I and 51 patients in Group II. Both
      groups were comparable at baseline. Hepatotoxicity was 44% in Group 6H and 29% in
      Group 3HR (P = 0.07). Hepatotoxicity was severe in 6.7% of Group 6H and 5.8% of
      Group 3HR, requiring treatment interruption in 4.4% and 1.9%, respectively (P =
      NS). Among the total, 75.6% of patients in group 6H, and 90.2% in group 3HR
      completed the study treatment (P = 0.05). Tuberculous disease was detected in
      only one patient in the 6H group, occurring in the second month of treatment.
      CONCLUSION: In the treatment of latent tuberculosis infection, a 3-month course
      of isoniazid plus rifampin resulted in better adherence and a lower percentage of
      discontinued treatments than a 6-month isoniazid course. Tolerance was similar in
      the two regimens.

PMID- 17504684
TI  - [Detection and genotyping of high-risk human papillomavirus in cervical
      specimens].
AB  - INTRODUCTION: This study investigates the relationship between various human
      papillomavirus (HPV) genotypes and the results of cytological and histological
      analysis of cervical samples using two complementary assays for HPV detection
      (hybrid capture and PCR). We studied the impact of HPV genotype on the presence
      of pre-cancerous cervical lesions and cervical cancer, as well as the association
      between HPV viral load and the presence of high-risk HPV as determined by PCR.
      METHODS: A total of 272 women were studied. Most of them presented cellular
      alterations consistent with cervical lesions due to HPV and all had high-risk HPV
      as detected by hybrid capture testing. Histological studies were undertaken, and
      HPV genotyping by PCR based on microarrays was performed. RESULTS: HPV-DNA was
      not detected or genotypes could not be identified by PCR in 22.06% of the
      patients. Genotype 16 and/or 18 was detected in 33% of 212 patients. Mixed
      infections with several genotypes were found in 25% of patients. The histological
      lesions associated with the various genotypes were as follows: genotype 16 and/or
      18. were detected in 55.73% of the 61 patients with H-SIL and cancer, whereas
      these genotypes were detected in only 7.9% and 22% of women with ASCUS and L-SIL
      (P < 0.05). Viral load was less than 3 pg/mL in 12.13% of the women studied. In
      this group of patients, high-risk HPV was present in 39.39%. In the group of
      patients who had a viral load greater than 3 pg/mL, high risk-HPV was detected in
      77.4% (P < 0.05). CONCLUSIONS: Genotypes 16 and/or 18 were detected in most
      patients with a diagnosis of H-SIL. Other high-risk-HPV genotypes were much less
      prevalent. Hybrid capture testing is a useful screening test. PCR was effective
      for identifying genotypes 16 and 18. Histological and cytological findings in
      cervical samples should be interpreted together with high-risk HPV detection.

PMID- 17504683
TI  - [Randomized clinical trial investigating three chemoprophylaxis regimens for
      latent tuberculosis infection in HIV-infected patients].
AB  - OBJECTIVE: To evaluate the adherence to, and safety of three chemoprophylaxis
      regimens for latent tuberculosis (TB) infection in HIV-infected patients with a
      positive tuberculin skin test. PATIENTS AND METHODS: A randomized, comparative,
      open clinical assay was carried out in 316 HIV-infected patients in 12 Spanish
      hospitals. Patients were randomly assigned to one of three regimens, 108 to
      isoniazid for six months (6H), 103 to rifampin and isoniazid for three months
      (3RH), and 105 to rifampin and pyrazinamide for two months (2RZ). After
      completion of treatment, patients were followed-up for two years. RESULTS: The
      period of observation following completion of treatment was 115, 108 and 101
      person-years for 6H, 3RH and 2RZ, respectively. Twenty-seven percent of patients
      voluntarily abandoned chemoprophylaxis and 9.7% were withdrawn due to adverse
      side-effects or interactions. Seven patients were withdrawn due to hepatotoxicity
      (5 in 6H, 2 in 3RH and 0 in 2RZ). No appreciable differences were found among the
      three regimens. There were 11 cases of tuberculosis during follow-up. The TB
      rates (cases per 100 person-years) in the three treatment groups were 3.48 in 6H,
      4.63 in 3RH and 1.98 in 2RZ. With respect to 2RZ, the relative risk for TB in the
      6H and 3RH regimens was 1.76 and 2.34, respectively. CONCLUSIONS: The safety of
      the 2RZ regimen for prophylaxis of latent TB infection in HIV patients was
      similar to that of the 6H and 3RH regimens. The incidence of hepatotoxicity was
      not higher in patients who received 2RZ.

PMID- 17504685
TI  - [Seroprevalence of viral hepatitis in a representative general population of an
      urban public health area in Castilla y Leon (Spain)].
AB  - INTRODUCTION: Viral hepatitis is a major social, health and economic problem
      worldwide, requiring strict epidemiological control. METHODS: This study presents
      the viral hepatitis seroprevalence in a representative sample from an urban
      health care area in Valladolid (Spain). RESULTS: Antibody prevalence was as
      follows: anti-HAV 52%; anti-HBc, 8.2%; anti-HCV, 1.1%; anti-HEV, 0.8%; and anti
      HGV 5.8%. Prevalence of anti-HAV, anti-HBc and anti-HGV increased significantly
      with age (P < 0.005 in all cases). In individuals younger than 20, prevalence of
      anti-HAV was 3.8%, anti-HBc < 0.28% and anti-HGV 1.3%. In the 20-39 year-old
      group, seroprevalence against HAV was associated with low educational levels (P =
      0.009) and with birth in other provinces (P = 0.016). Anti-HBc seroprevalence was
      mainly associated with three factors: prior hospitalization before 1990 (P =
      0.002; OR 3.32 [1.48-7.42]); compulsory military service before 1990 (P < 0.0001;
      OR 37.33 [3.68-378.03]); and acupuncture treatments (P = 0.018; OR 57.75 [26.17
      127.42]). Seroprevalence against HGV was associated with hospitalizations before
      1990 (P = 0.019; OR = 2.969 [1.154-7.639]). Seropositive status to HCV revealed a
      transfusion history (2 cases), hospitalization (1 case) or drug addiction (1
      case). Only one case among those seropositive to HEV had a history of a prior
      trip to a HEV-endemic area. CONCLUSIONS: Our study shows that the seroprevalences
      of viral hepatitis in a representative sample of urban population of Castille and
      Leon are similar to the seroprevalences observed in the rest of Spain and other
      developed countries, lower than the ones observed in the studies performed in
      Spain in the last 20 years due to the measures of prophylaxis that were taken.

PMID- 17504686
TI  - [Surgical treatment of lipodystrophy associated with HIV-infection: conclusions
      of a multidisciplinary meeting].
AB  - To discuss the treatment for lipodystrophy associated with antiretroviral
      therapy, a meeting was held among infectious disease specialists, plastic
      surgeons and psychologists with extensive expertise in the care of HIV-infected
      patients. Lipodystrophy has an important impact on the patients' quality of life.
      There is now sufficient experience with surgical correction of facial lipoatrophy
      to consider it a useful technique for these patients. This treatment should be
      provided to patients with moderate to severe lipoatrophy, and to certain patients
      with mild lipoatrophy under special circumstances. There are no indications for
      correcting lipoatrophy of the limbs. Ultrasound-assisted liposuction is the
      technique of choice for the treatment of lipohypertrophy and is indicated in
      patients with mechanical or functional abnormalities. Patients with clear
      indications should have access to the surgical techniques that have proven to be
      useful for correcting lipodystrophy.

PMID- 17504687
TI  - [Diagnosing imported helminthiasis].
AB  - In recent years, there has been an increase in cases of imported helminthiasis in
      Spain because of two complementary causes: immigration and international travel.
      Although the prevalence of helminthiasis is high in the immigrant population, the
      risk of transmission to the Spanish population is low. In this review, we provide
      clues to aid in the diagnosis of the helminthiasis, highlighting the geographic
      characteristics, clinical findings and analytical results of the most frequent
      types. The low sensitivity of the classic parasitological diagnostic test, mainly
      in tissue helminthiasis, is described. In addition, the advantages and
      limitations of the common serological methods for detecting related circulating
      antigens and antibodies are presented. Certain molecular methods used in the
      diagnosis of imported helminthiasis and the best strategies for screening of this
      condition are discussed.

PMID- 17504688
TI  - [Microbiological procedures for diagnosing mycoses and for antifungal
      susceptibility testing].
AB  - Fungal infections are a diagnostic and therapeutic problem of increasing concern
      due to the frequency and severity of disseminated infection in immunocompromised
      patients. Culture-based methods are characteristically slow and have poor
      sensitivity; hence, other methods, based on the detection of fungus-specific
      genetic, antigenic and metabolic components are being developed to enable early
      diagnosis and specific treatment. Moreover, reproducible antifungal
      susceptibility methods that can be adapted for use in clinical laboratories have
      been standardized to allow in vitro detection of resistance, which correlates
      with a less favorable clinical outcome. In this paper we review the main
      microbiological procedures available for the diagnosis of fungal infections and
      for antifungal susceptibility testing.

PMID- 17504689
TI  - [Warty epidermal hyperplasia in a kidney transplant recipient].

PMID- 17504690
TI  - [Nasal septal perforation in a Bolivian patient].

PMID- 17504691
TI  - [Infections in recipients of a kidney-pancreas transplant].
AB  - Infection can lead to graft loss and death in patients undergoing kidney and
      double kidney-pancreas transplantation. In this review, the prophylactic
      measures, the post-transplant timeline for the development of infections, and the
      most frequent infectious complications in patients with kidney and pancreas
      transplantation are described. Although great advances have been achieved in the
      prevention of infections, new problems have developed. Nosocomial bacterial
      infection with multidrug-resistant bacteria is an emerging complication.
      Cytomegalovirus is still the most frequent viral infection despite the advances
      in prevention measures. Moreover, in recent years polyomavirus type BK infection
      has been recognized as a major cause of renal graft loss. Knowledge of the
      infectious complications associated with these transplants and the risk factors
      for their occurrence will allow optimal therapeutic management of this patient
      population.

PMID- 17504692
TI  - [Lung infection due to MAC in a patient with no predisposing factors].

PMID- 17504693
TI  - Resistance to quinolones in Salmonella infantis due to overexpression of an
      active efflux system and a mutation in the gyrA gene.

PMID- 17504694
TI  - [Correlations among itraconazole, voriconazole and posaconazole MICs in
      Aspergillus fumigatus].

PMID- 17504695
TI  - [Streptococcus pneumoniae bacteremia secondary to a subcutaneous infection from a
      central venous catheter].

PMID- 17504696
TI  - [Cefepime and aztreonam shortages: we've run out of ammo].

PMID- 17504697
TI  - [Q fever following a tick bite].

PMID- 17504698
TI  - [Vascular malformations (I). Concept, classification, pathogenesis and clinical
      features].
AB  - Vascular malformations are anomalies always present at birth that, contrary to
      hemangiomas, never regress and may grow during lifetime. Clinical presentation of
      vascular malformations is extremely variable and ranges from asymptomatic spots
      of mere aesthetic concern to lesions with high blood flow or located in critical
      sites that may be life-threatening. Given the low incidence of these disorders it
      is difficult to establish therapeutic guidelines. In addition to a correct
      classification of vascular anomalies, it is necessary a multidisciplinary
      approach for the follow-up and management of these patients. The first part of
      this review focuses on the different classifications of vascular anomalies,
      maintaining as reference the one proposed by the International Society for the
      Study of Vascular Anomalies (ISSVA). Additionally, clinical features of the
      different subtypes of vascular anomalies as well as their association in certain
      syndromes are reviewed.

PMID- 17504699
TI  - [Dermatology and primary care: an obligatory relationship].

PMID- 17504700
TI  - [Consensus document on bath-PUVA therapy. The Spanish Photobiology Group of the
      Spanish Academy of Dermatology and Venereology].
AB  - Bath PUVA is a variant of phototherapy as efficacious as oral PUVA therapy that
      avoids many of the adverse effects associated to this treatment. Nevertheless,
      the special features and the specialized equipment required for its employment
      have limited its application in the dermatologic clinics of our country.
      Following the trend initiated after the publication of the consensus document on
      oral PUVA therapy and narrow band (NB) UVB therapy, the Spanish Photobiology
      Group from the Spanish Academy of Dermatology and Venereology has developed a
      therapeutic guideline for bath PUVA therapy based on the literature review and
      the experience of its members. The document aims to be a practical reference
      guide for those dermatological centres that include phototherapy among their
      services. It reviews the concept and indications of this type of treatment and
      proposes recommendations concerning therapeutic procedures, drug associations of
      interest and prophylaxis and management of adverse effects.

PMID- 17504701
TI  - [Minor cutaneous ambulatory surgery and cryotherapy. Comparative study between a
      dermatologist and family physicians].
AB  - INTRODUCTION: Lack of diagnostic skill in cutaneous surgery may lead to erroneous
      and potentially detrimental therapies. This study compares the diagnosis and
      treatment in cutaneous surgery, including cryotherapy, between a dermatologist
      and family physicians. METHODS: It is an observational, prospective study on a
      random sample of patients that consulted the dermatologist for candidate lesions.
      Each lesion was independently evaluated by a dermatologist and a family
      physician, both of whom assigned the clinical diagnosis and therapeutic advice.
      Concordance for diagnosis, recommended treatment and indication for cryotherapy
      was calculated by Cohen's kappa coefficient. RESULTS: Six hundred forty-six
      lesions were evaluated. Global kappa indexes were 0.69 (95 % CI, 0.65-0.73) for
      diagnostic concordance, 0.62 (95 % CI, 0.56-0.67) for recommended treatment and
      0.73 (95 % CI, 0.67-0.78) for indication of cryotherapy. Diagnostic concordance
      was significantly better for melanocytic nevus, achrocordon and for lesions with
      multiple and monomorphous presentation, and worse for isolated pigmented lesions.
      For recommended treatment concordance was better for multiple and monomorphous
      lesions and worse for skin cancer and seborrheic keratosis. For indication of
      cryotherapy concordance was worse for skin cancer, melanocytic nevus, acrochordon
      and seborrheic keratosis. Family physicians made an erroneous indication for
      cryotherapy in 5.88 % of cases, including 3 non melanoma skin cancers.
      CONCLUSIONS: Concordance between dermatologists and family physicians for minor
      cutaneous surgery is generally good. Family physicians should be more careful in
      evaluating solitary pigmented lesions and patients at risk for skin cancer.

PMID- 17504702
TI  - [Eruptive pseudoangiomatosis: study of 7 cases].
AB  - INTRODUCTION: Eruptive pseudoangiomatosis consists in the acute development of
      small vascular lesions in the face and extremities that resolve in several weeks
      without scarring. Lesions are described as 3-4 mm asymptomatic macules and
      papules with peripheral whitish halo that blanch upon pressure. Initially it was
      considered a disease limited to children but it has also been described in
      adults. It overlaps with the entity known in Japan as <<erythema punctatum
      Higuchi>>, possibly caused by an insect named Culex pipiens pallens. METHODS: We
      report a serie of 7 patients that consulted for lesions compatible with eruptive
      pseudoangiomatosis. We performed a detailed clinical history and histological,
      microbiological and serological studies. Follow-up time was up to 4 years.
      RESULTS: Eighty-five percent of patients were women and the mean age was 62
      years. All cases appeared in spring/summer and 71 % relapsed. Lesions
      predominated in the face and extremities and the outbreak lasted 2-4 weeks. The
      anamnesis did not disclose any specific etiologic agent in any of the cases.
      Complete laboratory tests including serologies and cultures were negative or
      within normal limits. Histological study revealed vascular dilatation in all
      cases with endothelial cell protrusion and a peripheral lymphohistiocytic
      infiltrate. CONCLUSIONS: Currently, the etiology of this entity is not well
      established although it probably represents a reactive disorder to different
      etiologic processes.

PMID- 17504703
TI  - [Trichothiodystrophy: PIBIDS syndrome].
AB  - Trichothiodystrophy comprises a heterogeneous group of autosomal recessive
      entities. This fact gives rise to different interrelated neuroectodermal
      disorders. From a structural point of view these features are the result of the
      low tissue sulfur content. We report a case of trichothiodystrophy initially
      classified as Tay syndrome that based on clinical features, complementary exams
      as well as on the disease evolution was labelled as PIBIDS syndrome.

PMID- 17504705
TI  - [Primary cutaneous anaplastic CD30+ large cell lymphoma].
AB  - Primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) is part of the
      spectrum of primary cutaneous CD30+ lymphoproliferative disorders together with
      lymphomatoid papulosis. It affects mainly elderly patients and presents as skin
      nodules that tend to ulcerate. Histological and immunohistochemical study show
      the expression of CD30 antigen in more than 75 % of neoplastic cells. Currently
      it is considered a low grade lymphoma with favourable prognosis and good response
      to treatments such as local radiotherapy, methotrexate or surgery. We report a 93
      year-old patient with ulcerated nodules in her right leg. Histological and
      immunohistochemical study confirmed the diagnosis of PCALCL, of non-B, non-T
      origin. The patient was treated with local radiotherapy with progressive
      resolution of skin nodules and absence of relapse at 6 months follow-up.

PMID- 17504704
TI  - [Sporotrichoid cutaneous infection by Mycobacterium haemophilum in an AIDS
      patient].
AB  - We report a case of primary cutaneous infection by Mycobacterium haemophilum
      after the bite of an aquarium fish in a severely immunodepressed AIDS patient.
      Clinical features consisted in nodular and ulcerative lesions that followed a
      sporotrichoid pattern. Histological study of nodular lesions showed a
      granulomatous dermatitis with numerous acid-fast bacilli. The mycobacterium was
      identified 3 months later by genetic hybridization from a cultive in solid
      medium. Combined therapy with isoniazid, rifampin, clarithromycin, ethambutol,
      amikacin and ciprofloxacin resulted in complete resolution of the lesions.
      Infection by Mycobacterium haemophilum is a rare mycobacteriosis that usually
      affects immunodepressed patients. The most common clinical manifestations are
      cutaneous lesions but the development of sporotrichoid nodular lymphangitis is
      exceptional.

PMID- 17504706
TI  - [Woolly hair nevus associated with an ipsilateral linear epidermal nevus].
AB  - We report a 4-year-old boy with two areas of woolly hair in the right
      parietotemporal region and a linear epidermal nevus in the areas of woolly hair
      as well as in the ipsilateral hemiface and chin. Evaluation by scanning electron
      microscopy showed woolly hair with oval transverse section and longitudinal
      groove. A complete examination ruled out associated anomalies.

PMID- 17504707
TI  - [Hyperpigmented axillary papules].

PMID- 17504708
TI  - [Plantar erythematosquamous plaque].

PMID- 17504709
TI  - [Multiple terminal hair cysts in perianal region].

PMID- 17504710
TI  - [Leser-Trelat sign associated with Sezary syndrome and transitional cell
      carcinoma of the bladder].

PMID- 17504711
TI  - [Gastric adenocarcinoma presenting as generalized cutaneous metastases].

PMID- 17504712
TI  - [Behcet's disease and periarteritis nodosa with cutaneous lesions].

PMID- 17504713
TI  - The median artery: its potential implications for the radial forearm flap.
AB  - The median artery is an infrequent anomaly with a highly variable origin and
      course in the forearm. It is associated with other local anatomical variations,
      and may contribute significantly to the superficial palmar arch. We describe the
      incidental finding of a palmar median artery during harvesting of a radial
      forearm flap despite normal preoperative Allen's test and colour Doppler
      ultrasonography. A review of the anatomy and embryology suggests that there is an
      association of a persistent palmar median artery and an incomplete palmar arch,
      and that the median artery may arise from the radial artery, leading to an
      increased risk of hand ischaemia if it is sacrificed during harvesting. In this
      case the origin of the median artery was not encountered, and the patient did not
      develop ischaemia. We suggest that in the event of finding such an artery, the
      surgeon must be vigilant in order to ensure its origin is not ligated during
      harvesting.

PMID- 17504714
TI  - Obesity and the skin: skin physiology and skin manifestations of obesity.
AB  - Obesity is widely recognized as an epidemic in the Western world; however, the
      impact of obesity on the skin has received minimal attention. The purpose of this
      article is to highlight the association between obesity and dermatologic
      conditions. We review the impact of obesity on the skin, including skin
      physiology, skin manifestations of obesity, and dermatologic diseases aggravated
      by obesity. Obesity is responsible for changes in skin barrier function,
      sebaceous glands and sebum production, sweat glands, lymphatics, collagen
      structure and function, wound healing, microcirculation and macrocirculation, and
      subcutaneous fat. Moreover, obesity is implicated in a wide spectrum of
      dermatologic diseases, including acanthosis nigricans, acrochordons, keratosis
      pilaris, hyperandrogenism and hirsutism, striae distensae, adiposis dolorosa, and
      fat redistribution, lymphedema, chronic venous insufficiency, plantar
      hyperkeratosis, cellulitis, skin infections, hidradenitis suppurativa, psoriasis,
      insulin resistance syndrome, and tophaceous gout. We review the clinical
      features, evidence for association with obesity, and management of these various
      dermatoses and highlight the profound impact of obesity in clinical dermatology.
      LEARNING OBJECTIVE: After completing this learning activity, participants should
      be aware of obesity-associated changes in skin physiology, skin manifestations of
      obesity, and dermatologic diseases aggravated by obesity, and be able to
      formulate a pathophysiology-based treatment strategy for obesity-associated
      dermatoses.

PMID- 17504715
TI  - Intralesional methotrexate treatment for keratoacanthoma tumors: a retrospective
      study and review of the literature.
AB  - BACKGROUND: Intralesional methotrexate (MTX) is an effective treatment for
      keratoacanthoma (KA). OBJECTIVE: We sought to systematically examine response
      rates and adverse events in KA treated with intralesional MTX. METHODS: All cases
      of KA treated with intralesional MTX at our institution from 1991 to 2006 were
      identified. A MEDLINE and PubMed search of cases of KA treated with intralesional
      MTX was also performed. RESULTS: In all, 38 cases of KA treated with
      intralesional MTX were identified: 18 from our institution and 20 from the
      literature. Intralesional MTX achieved resolution in 92%, requiring an average of
      2.1 injections an average of 18 days apart. Adverse events were rare, with two
      reports of pancytopenia in patients with chronic renal failure. LIMITATIONS: Use
      of single case reports, small series, and retrospective analysis are limitations.
      CONCLUSION: Intralesional MTX is a useful nonsurgical therapy for the treatment
      of KA. Histologic diagnosis before initiation of treatment is preferred. A
      complete blood cell count at baseline and during treatment should be considered
      to monitor for potential cytopenia.

PMID- 17504716
TI  - Prolonged urticaria with purpura: the spectrum of clinical and histopathologic
      features in a prospective series of 22 patients exhibiting the clinical features
      of urticarial vasculitis.
AB  - BACKGROUND: Biopsy specimens of lesions with clinical features of urticarial
      vasculitis often show a predominantly lymphocytic infiltrate with eosinophils and
      red blood cell extravasation. Only occasionally is a leukocytoclastic vasculitis
      encountered, confirming a diagnosis of urticarial vasculitis. OBJECTIVE: The aim
      of this study was to assess the clinical presentation and histologic features of
      patients who meet the clinical criteria for urticarial vasculitis. METHODS:
      Patients were recruited who had persistent urticarial lesions individually
      lasting longer than 24 hours, associated with at least 2 of 3 of the following:
      pain or tenderness; purpura or dusky changes; and resolution with
      hyperpigmentation. Patients were interviewed based on a standard questionnaire
      with regard to their symptoms. Blood tests and chest radiographs were performed
      to exclude systemic involvement and hypocomplementemia. Skin biopsy specimens
      were sent for histology and direct immunofluorescence. RESULTS: Of 22 patients
      recruited, 19 (86.4%) showed a predominantly lymphocytic infiltrate on histology.
      Three cases (13.6%) had a neutrophil-predominant infiltrate associated with a
      leukocytoclastic vasculitis. Twenty (90.9%) had a superficial perivascular
      infiltrate, and two (9.1%) had a superficial and deep perivascular infiltrate. In
      all, 21 biopsy specimens (95.5%) showed inflammatory cells within dermal blood
      vessel walls, obscuring the vessel outline in some. Endothelial cell swelling was
      seen in 20 biopsy specimens (90.9%), erythrocyte extravasation in 17 (77.3%),
      nuclear dust in 5 (22.7%), and fibrin extravasation in 2 (9.1%). Multivariate
      analysis revealed the following features to be independently associated with
      neutrophil predominance: fulfillment of all 3 minor criteria for urticarial
      vasculitis-like lesions (P = .007); presence of fibrin on histology (P < .001);
      presence of nuclear dust on histology (P = .001); hypocomplementemia (P = .001);
      and anemia (P = .015). There was a trend toward lesions not clearing as readily
      in the neutrophil-predominant group (P = .071), even with two-modality treatment
      (P = .089). LIMITATIONS: Serum immunoelectrophoresis was not done to exclude
      Schnitzler's syndrome. Electronmicroscopy and cytokine profiling were not
      performed. CONCLUSION: Biopsy specimens of lesions with clinical features of
      urticarial vasculitis reveal that only a minority of patients has
      leukocytoclastic vasculitis. The majority has a lymphocyte-predominant histology,
      associated with varying numbers of eosinophils. We favor a lymphocytic vasculitis
      as a causative explanation in the lymphocyte-predominant group.

PMID- 17504717
TI  - Mast cell distribution, activation, and phenotype in xanthoma.
AB  - BACKGROUND: Activated mast cells enhance the uptake of mast cell-derived
      proteoglycan-low-density lipoprotein complexes by macrophages. OBJECTIVE: We
      sought to investigate mast cell contribution to the pathogenesis of xanthoma.
      METHODS: Twenty cases of xanthelasma palpebrarum and 6 cases of tuberous xanthoma
      lesions were analyzed using immunohistochemical staining. RESULTS: Xanthelasma
      lesions contained up to 5-fold more tryptase-stained mast cells than tuberous
      xanthoma lesions. Tuberous xanthoma lesions especially showed extensive staining
      of tryptase around mast cells and within some macrophages and foam cells. More
      than 99% of mast cells in xanthelasma lesions contained both tryptase and
      chymase. Approximately 60% of mast cells represented only tryptase in tuberous
      xanthoma lesions where the ratio of macrophages to tryptase-stained mast cells
      was extremely high (15:1) as compared with xanthelasma lesions (2:1).
      LIMITATIONS: A change in mast cell phenotype has not been necessarily proven.
      CONCLUSION: Mast cells are activated under the microenvironment in which
      macrophages predominate rather than mast cells, which thus reflects the clinical
      phenotypes of xanthoma lesions.

PMID- 17504718
TI  - Cutaneous lupus erythematosus simulating squamous neoplasia: the
      clinicopathologic conundrum and histopathologic pitfalls.
AB  - BACKGROUND: The clinical distribution and character of cutaneous lupus
      erythematosus lesions can simulate squamous neoplasms, leading physicians to
      submit a shave biopsy specimen with a differential diagnosis of squamous
      neoplasm. OBJECTIVE: Our aim was to describe histologic features of interface
      dermatitis that cause difficulty in distinguishing between cutaneous lupus
      erythematosus and squamous neoplasia in shave biopsy specimens and to identify
      distinguishing criteria. METHODS: Twenty-six biopsy specimens from 10 patients
      initially diagnosed with squamous neoplasia that ultimately proved to be
      cutaneous lupus erythematosus were identified. Comparisons were made of these to
      38 control biopsies of chronic cutaneous lupus erythematosus and 34 control
      biopsies of keratoses/carcinomas without lupus. All biopsies were scored (0 or 1:
      absent or present) with respect to 11 histologic criteria. RESULTS: The criteria
      of perifollicular inflammation, follicular plugging, vacuolar interface change,
      compact orthokeratosis, and acrosyringeal inflammation were significantly more
      common in the lupus cases than in the keratoses/carcinomas controls. The mean
      lupus case score was 6.88, lupus control score 6.55, and keratoses/carcinomas
      control score 5.08. LIMITATIONS: A limited number of patients were studied.
      Microscopic observations and assumptions with inherent subjectivity were used in
      establishing the histologic scores. CONCLUSION: Use of the criteria presented,
      although not absolute, should alert one to the possibility of lupus in an
      atypical squamous proliferation, especially in suspected squamous neoplasms that
      worsen or recur after therapy.

PMID- 17504719
TI  - Folliculosebaceous smooth muscle hamartoma.
AB  - Cutaneous hamartomas are a group of heterogenous benign skin conditions
      demonstrating epithelial and mesenchymal components in varying proportions.
      Folliculosebaceous (cystic) hamartomas comprise a distinct group of uncommon
      cutaneous tumor-like malformations. Histologically, these lesions demonstrate
      varying proportions of adnexal and stromal tissues. We review the literature on
      folliculosebaceous hamartoma and report a case with smooth muscle as its only
      stromal component.

PMID- 17504720
TI  - Oral contraceptives for the treatment of acne vulgaris.

PMID- 17504721
TI  - Of spiders and zebras: publication of inadequately documented loxoscelism case
      reports.
AB  - The dermatology and general medical literature is filled with articles that
      report skin disease caused by the brown recluse spider, Loxosceles reclusa. A
      large number of these articles contain inadequate documentation of Loxosceles
      bites; many come from areas that have no Loxosceles spiders. Authors submitting
      papers alleging loxoscelism should adhere to standards of evidence when writing
      case reports.

PMID- 17504722
TI  - Bazex syndrome or dermatomyositis?

PMID- 17504723
TI  - Current strategies to address the ongoing shortage of academic dermatologists.

PMID- 17504724
TI  - Head-to-head studies of botulinum toxin A in aesthetic medicine: which evidence
      is good enough?

PMID- 17504725
TI  - The merits of adding toluidine blue-stained slides in Mohs surgery in the
      treatment of a microcystic adnexal carcinoma.

PMID- 17504726
TI  - Is apoptosis involved in the development of balloon cell nevus? Suggestion from a
      case report.

PMID- 17504727
TI  - Symptomatic response of erythropoietic protoporphyria to iron supplementation.

PMID- 17504728
TI  - Squamous cell carcinoma over tattoos.

PMID- 17504729
TI  - Transition from acute to chronic pain and disability: a model including
      cognitive, affective, and trauma factors.
AB  - This study evaluated a theoretically and empirically based model of the
      progression of acute neck and back pain to chronic pain and disability, developed
      from the literature in chronic pain, cognition, and stress and trauma. Clinical
      information and standardized psychosocial measures of cumulative traumatic events
      exposure (TLEQ), depressed mood (CES-D), pain (DDS), physical disability (PDI),
      and pain beliefs (PBPI) were collected at baseline from 84 acute back pain
      patients followed at an Acute Back Clinic over 3 months. Path analysis was used
      for the longitudinal prediction of perceived pain and disability. The predictive
      model accounted for 26% of the variance in persistent pain intensity and 58% of
      the variance in perceived physical disability at 3 months. Greater exposure to
      past traumatic life events and depressed mood were most predictive of chronic
      pain; depressed mood and negative pain beliefs were most predictive of chronic
      disability. More cumulative traumatic life events, higher levels of depression in
      the early stages of a new pain episode, and early beliefs that pain may be
      permanent significantly contribute to increased severity of subsequent pain and
      disability. Replication in a larger sample is desirable to confirm these paths.
      Early detection of elevated depressive symptoms and high trauma exposure may
      identify individuals at greater risk for developing chronic pain syndromes who
      may benefit from early multidisciplinary intervention.

PMID- 17504730
TI  - It is time to move: linking flight and foraging behaviour in a diving bird.
AB  - Although the adaptive value of flight may seem obvious, it is the most difficult
      behaviour of birds to monitor. Here, we describe a technique to quantify the
      frequency and the duration of flights over several months by implanting a data
      logger that records heart rate (fH), hydrostatic pressure (diving depth) and the
      body angle of a large sea duck species, the common eider (Somateria mollissima).
      According to the mean fH recorded during flight and the parameters recorded to
      identify the fH flight signature, we were able to identify all flights performed
      by 13 individuals during eight months. We cumulated local flight time (outside
      migrations) and found that activity occurs primarily during dawn and morning and
      that flying activities are strongly related to diving activities (Pearson's
      r=0.88, permutation test p<0.001). This relationship was interpreted as a
      consequence of living in a dynamic environment where sea currents move the ducks
      away from the food patches. We believe that the technique described here will
      open new avenues of investigation in the adaptive value of flight.

PMID- 17504731
TI  - Antimicrobial defences increase with sociality in bees.
AB  - Evidence for the antiquity and importance of microbial pathogens as selective
      agents is found in the proliferation of antimicrobial defences throughout the
      animal kingdom. Social insects, typified by crowding and often by low genetic
      variation, have high probabilities of disease transmission and eusocial
      Hymenoptera may be particularly vulnerable because of haplodiploidy. Mechanisms
      they employ to reduce the risk of disease include antimicrobial secretions which
      are particularly important primary barriers to infection. However, until now,
      whether or not there is selection for stronger antimicrobial secretions when the
      risk of disease increases because of sociality has not been tested. Here, we
      present evidence that the production of progressively stronger antimicrobial
      compounds was critical to the evolution of sociality in bees. We found that
      increases in group size and genetic relatedness were strongly correlated with
      increasing antimicrobial strength. The antimicrobials of even the most primitive
      semi-social species were an order of magnitude stronger that those of solitary
      species, suggesting a point of no return, beyond which disease control was
      essential. Our results suggest that selection by microbial pathogens was critical
      to the evolution of sociality and required the production of strong, front-line
      antimicrobial defences.

PMID- 17504732
TI  - Positive natural selection has driven the evolution of the Hsp70s in Diguetia
      spiders.
AB  - Hsp70s are a ubiquitous family of highly conserved proteins. Hsp70s are
      chaperones and have important roles in both protein folding and thermotolerance.
      It has been widely assumed that Hsp70 sequence evolution is governed by the
      strong functional constraints imposed by its crucial cellular functions. In this
      study of cytosolic heat-inducible Hsp70s from three spider families, we have
      found clear evidence of positive natural selection altering Hsp70s in desert
      dwelling and heat-loving Diguetidae spiders. These spiders are a small family
      restricted to deserts. They display heat-tolerant behaviours not seen in their
      closest relatives, the Pholcidae and Plectreuridae.

PMID- 17504733
TI  - From cradle to early grave: juvenile mortality in European shags Phalacrocorax
      aristotelis results from inadequate development of foraging proficiency.
AB  - In most long-lived animal species, juveniles survive less well than adults. A
      potential mechanism is inferior foraging skills but longitudinal studies that
      follow the development of juvenile foraging are needed to test this. We used
      miniaturized activity loggers to record daily foraging times of juvenile and
      adult European shags Phalacrocorax aristotelis from fledging to the following
      spring. Juveniles became independent from their parents 40 days post-fledging.
      They compensated for poor foraging proficiency by foraging for approximately 3 h
      d(-1) longer than adults until constrained by day length in early November.
      Thereafter, juvenile foraging time tracked shortening day length up to the winter
      solstice, when foraging time of the two age classes converged and continued to
      track day length until early February. Few individuals died until midwinter and
      mortality peaked in January-February, with juvenile mortality (including some of
      the study birds) five times that of adults. In their last two weeks of life,
      juveniles showed a marked decline in foraging time consistent with individuals
      becoming moribund. Our results provide compelling evidence that juveniles
      compensate for poor foraging proficiency by increasing foraging time, a strategy
      that is limited by day length resulting in high winter mortality.

PMID- 17504734
TI  - Psychological benefits of greenspace increase with biodiversity.
AB  - The world's human population is becoming concentrated into cities, giving rise to
      concerns that it is becoming increasingly isolated from nature. Urban public
      greenspaces form the arena of many people's daily contact with nature and such
      contact has measurable physical and psychological benefits. Here we show that
      these psychological benefits increase with the species richness of urban
      greenspaces. Moreover, we demonstrate that greenspace users can more or less
      accurately perceive species richness depending on the taxonomic group in
      question. These results indicate that successful management of urban greenspaces
      should emphasize biological complexity to enhance human well-being in addition to
      biodiversity conservation.

PMID- 17504735
TI  - A framework for evaluating animals as sentinels for infectious disease
      surveillance.
AB  - The dynamics of infectious diseases are highly variable. Host ranges, host
      responses to pathogens and the relationships between hosts are heterogeneous.
      Here, we argue that the use of animal sentinels has the potential to use this
      variation and enable the exploitation of a wide range of pathogen hosts for
      surveillance purposes. Animal sentinels may be used to address many surveillance
      questions, but they may currently be underused as a surveillance tool and there
      is a need for improved interdisciplinary collaboration and communication in order
      to fully explore the potential of animal sentinels. In different contexts,
      different animal hosts will themselves vary in their capacity to provide useful
      information. We describe a conceptual framework within which the characteristics
      of different host populations and their potential value as sentinels can be
      evaluated in a broad range of settings.

PMID- 17504736
TI  - Intact endothelial cell sheet harvesting from thermoresponsive surfaces coated
      with cell adhesion promoters.
AB  - Recently, with the development of smart polymers, research has looked to using
      thermoresponsive polymers as cell culture substrates. These novel surfaces allow
      the cultivation of cells without enzymes using the thermoresponsive phase
      transition property of poly(N-isopropylacrylamide) (PNIPAAm). However, this
      requires expensive techniques to generate a sufficiently thin film that allows
      cell adhesion. In this study, we looked at simple solvent cast films which
      normally show poor cell adhesion, but here the films are coated with cell
      adhesion promoters (CAPs) to improve cell growth without altering the copolymer
      thermoresponsive behaviour.A copolymer of PNIPAAm and N-tert-butylacrylamide
      (NtBAm) with a ratio of 85:15, respectively, was synthesized and solvent cast.
      The copolymer films were coated with CAPs, such as collagen, fibronectin and
      laminin, to increase their cell adhesion and growth properties. Cell activity
      measured by the alamarBlue assay showed similar results for coated copolymer
      films and standard tissue culture plastic controls. Deposition of CAPs on to the
      copolymer films was characterized by scanning electron microscopy and atomic
      force microscopy. Cell detachment from the copolymer films is not affected by the
      surface coatings of CAPs, and endothelial cells are recovered as an intact sheet,
      which has great potential for uses in tissue engineering applications. The
      results demonstrate a versatile method for the cultivation of cells while
      eliminating the need for the use of digestive enzymes such as trypsin. This study
      shows that cultivation on physically bonded PNIPAAm copolymers is viable and
      achievable by relatively simple methods.

PMID- 17504737
TI  - Time is of the essence: exploring a measles outbreak response vaccination in
      Niamey, Niger.
AB  - The current World Health Organization recommendations for response during measles
      epidemics focus on case management rather than outbreak response vaccination
      (ORV) campaigns, which may occur too late to impact morbidity and mortality and
      have a high cost per case prevented. Here, we explore the potential impact of an
      ORV campaign conducted during the 2003-2004 measles epidemic in Niamey, Niger. We
      measured the impact of this intervention and also the potential impact of
      alternative strategies. Using a unique geographical, epidemiologic and
      demographic dataset collected during the epidemic, we developed an individual
      based simulation model. We estimate that a median of 7.6% [4.9-8.9] of cases were
      potentially averted as a result of the outbreak response, which vaccinated
      approximately 57% (84563 of an estimated 148600) of children in the target age
      range (6-59 months), 23 weeks after the epidemic started. We found that
      intervening early (up to 60 days after the start of the epidemic) and expanding
      the age range to all children aged 6 months to 15 years may lead to a much larger
      (up to 90%) reduction in the number of cases in a West African urban setting like
      Niamey. Our results suggest that intervening earlier even with lower target
      coverage (approx. 60%), but a wider age range, may be more effective than
      intervening later with high coverage (more than 90%) in similar settings. This
      has important implications for the implementation of reactive vaccination
      interventions as they can be highly effective if the response is fast with
      respect to the spread of the epidemic.

PMID- 17504738
TI  - Genetic and environmental contributions to population group differences on the
      Raven's Progressive Matrices estimated from twins reared together and apart.
AB  - We carried out two studies to test the hypothesis that genetic and environmental
      influences explain population group differences in general mental ability just as
      they do individual differences within a group. We estimated the heritability and
      environmentality of scores on the diagrammatic puzzles of the Raven's Coloured
      and/or Standard Progressive Matrices (CPM/SPM) from two independent twin samples
      and correlated these estimates with group differences on the same items. In Study
      1, 199 pairs of 5- to 7-year-old monozygotic (MZ) and dizygotic (DZ) twins reared
      together provided estimates of heritability and environmentality for 36 puzzles
      from the CPM. These estimates correlated with the differences between the twins
      and 94 Serbian Roma (both rs=0.32; Ns=36; ps<0.05). In Study 2, 152 pairs of
      adult MZ and DZ twins reared apart provided estimates of heritability and
      environmentality for 58 puzzles from the SPM. These estimates correlated with the
      differences among 11 diverse samples including (i) the reared-apart twins, (ii)
      another sample of Serbian Roma, and (iii) East Asian, White, South Asian,
      Coloured and Black high school and university students in South Africa. In 55
      comparisons, group differences were more pronounced on the more heritable and on
      the more environmental items (mean rs=0.40 and 0.47, respectively; Ns=58;
      ps<0.05). After controlling for measurement reliability and variance in item pass
      rates, the heritabilities still correlated with the group differences, although
      the environmentalities did not. Puzzles found relatively difficult (or easy) by
      the twins were those found relatively difficult (or easy) by the others (mean
      r=0.87). These results suggest that population group differences are part of the
      normal variation expected within a universal human cognition.

PMID- 17504739
TI  - Host community structure and the maintenance of pathogen diversity.
AB  - Community structure has been widely identified as a feature of many real-world
      networks. It has been shown that the antigenic diversity of a pathogen population
      can be significantly affected by the contact network of its hosts; however, the
      effects of community structure have not yet been explored. Here, we examine the
      congruence between patterns of antigenic diversity in pathogen populations in
      neighbouring communities, using both a deterministic metapopulation model and
      individual-based formulations. We show that the spatial differentiation of the
      pathogen population can only be maintained at levels of coupling far lower than
      that necessary for the host populations to remain distinct. Therefore,
      identifiable community structure in host networks may not reflect differentiation
      of the processes occurring upon them and, conversely, a lack of genetic
      differentiation between pathogens from different host communities may not reflect
      strong mixing between them.

PMID- 17504740
TI  - Genetically resistant sheep avoid parasites to a greater extent than do
      susceptible sheep.
AB  - Livestock breeding programmes have created resistant (R) and susceptible (S)
      sheep that differ in their ability to control parasites through their immune
      function but potentially also their grazing behaviour (i.e. parasite avoidance).
      Using the Perendale genetic lines, we tested the hypothesis that R-sheep avoid
      parasites more effectively, reducing their parasite exposure/challenge, compared
      with S-sheep. However, in grazing systems, parasite-rich areas are also forage
      rich, suggesting that parasite avoidance behaviours are associated with
      nutritional penalties. We first created a naturally heterogeneous sward structure
      of gaps and tussocks and then used focal behavioural observations to quantify the
      sward selection of R- and S-sheep. Tussock swards were more nitrogen rich (41%),
      offered increased forage intake rates (32%) and contained 17 times more parasite
      larvae than gap swards. All the animals avoided grazing the tussock swards.
      However, the R-sheep grazed the tussock swards to a lesser degree than the S
      sheep. We conclude that selection for genetic resistance has resulted in animals
      that, despite being well armed to fight parasitism through improved immune
      function, adopt parasite avoidance strategies with associated nutritional
      disadvantages. This experiment highlights the role of host behaviour in the
      control of parasitism and suggests that animals can be bred to avoid disease.

PMID- 17504741
TI  - Participation costs dismiss the advantage of heterogeneous networks in evolution
      of cooperation.
AB  - Real social interactions occur on networks in which each individual is connected
      to some, but not all, of others. In social dilemma games with a fixed population
      size, heterogeneity in the number of contacts per player is known to promote
      evolution of cooperation. Under a common assumption of positively biased pay-off
      structure, well-connected players earn much by playing frequently, and
      cooperation once adopted by well-connected players is unbeatable and spreads to
      others. However, maintaining a social contact can be costly, which would prevent
      local pay-offs from being positively biased. In replicator-type evolutionary
      dynamics, it is shown that even a relatively small participation cost
      extinguishes the merit of heterogeneous networks in terms of cooperation. In this
      situation, more connected players earn less so that they are no longer spreaders
      of cooperation. Instead, those with fewer contacts win and guide the evolution.
      The participation cost, or the baseline pay-off, is irrelevant in homogeneous
      populations, but is essential for evolutionary games on heterogeneous networks.

PMID- 17504742
TI  - Reproductive isolation of sympatric morphs in a population of Darwin's finches.
AB  - Recent research on speciation has identified a central role for ecological
      divergence, which can initiate speciation when (i) subsets of a species or
      population evolve to specialize on different ecological resources and (ii) the
      resulting phenotypic modes become reproductively isolated. Empirical evidence for
      these two processes working in conjunction, particularly during the early stages
      of divergence, has been limited. We recently described a population of the medium
      ground finch, Geospiza fortis, that features large and small beak morphs with
      relatively few intermediates. As in other Darwin's finches of the Galapagos
      Islands, these morphs presumably diverged in response to variation in local food
      availability and inter- or intraspecific competition. We here demonstrate that
      the two morphs show strong positive assortative pairing, a pattern that holds
      over three breeding seasons and during both dry and wet conditions. We also
      document restrictions on gene flow between the morphs, as revealed by genetic
      variation at 10 microsatellite loci. Our results provide strong support for the
      central role of ecology during the early stages of adaptive radiation.

PMID- 17504743
TI  - Evolution of an avian pigmentation gene correlates with a measure of sexual
      selection.
AB  - The extravagant plumage traits of male birds are a favourite example of sexual
      selection. However, to date the units that selection is acting upon, the genes
      themselves have been a 'black box'. Here, we report evidence of change driven by
      sexual selection at a pigmentation gene locus in the galliform birds. Across
      species, we find a correlation between the rate of amino acid change (dN/dS) at
      this locus (MC1R) and the degree of sexual dichromatism, which we use as a
      measure of the strength of sexual selection. There is no evidence for a similar
      pattern in any of five other loci (four candidate and one control locus). This is
      consistent with previous work on colour polymorphisms and suggests that MC1R may
      be a key target for selection acting on plumage colour. The pattern of selection
      at MC1R seems to be consistent with the continuous or cyclical evolution of
      traits and preferences that is the outcome of several Fisherian and good-genes
      models of sexual selection. In contrast, we found no support for models of sexual
      selection that predict an increase in purifying selection as a result of purging
      of deleterious mutations or for models that predict an increased rate of mutation
      in association with stronger sexual selection.

PMID- 17504744
TI  - Neutron-induced dosimetry reaction cross-section measurements from the threshold
      up to 20 MeV.
AB  - New measured results were obtained for the (58)Ni(n,p)(58)Co, (58)Ni(n,2n)(57)Ni,
      (58)Ni(n,x)(57)Co, (60)Ni(n,p)(60)Co, (59)Co(n,2n)(58)Co, (59)Co(n,p)(59)Fe,
      (63)Cu(n,alpha)(60)Co, (204)Pb(n,n')(204 m)Pb and (204)Pb(n,2n)(203)Pb reaction
      cross-sections. These reactions may be of interest for dosimetry. Measurements
      were taken at the 7 MV Van de Graaff accelerator at IRMM, Geel, using the
      activation technique in combination with high-resolution gamma ray spectrometry.
      The present results are compared with other measurements, evaluated data and
      model calculations.

PMID- 17504745
TI  - The new hybrid thermal neutron facility at TAPIRO reactor for BNCT
      radiobiological experiments.
AB  - A new thermal neutron irradiation facility, devoted to carry out both dosimetric
      and radiobiological studies on boron carriers, which are being developed in the
      framework of INFN BNCT project, has been installed at the ENEA Casaccia TAPIRO
      research fast reactor. The thermal column, based on an original, hybrid, neutron
      spectrum shifter configuration, has been recently become operative. In spite of
      its low power (5 kW), the new facility is able to provide a high thermal neutron
      flux level, uniformly distributed inside the irradiation cavity, with a quite low
      gamma background. The main features and preliminary benchmark measurements of the
      Beam-shaping assembly are here presented and discussed.

PMID- 17504746
TI  - Neutron detection on the Foton-M2 satellite by a track etch detector stack.
AB  - In the frame of a European Space Agency (ESA) project called 'Biology and Physics
      in Space', a returning satellite, Foton-M2, was orbiting a container, the BIOPAN
      5, loaded with biological experiments and facilities for radiation dosimetry
      (RADO) in the open space. One of the RADO experiments was dedicated to the
      detection of the primary cosmic rays and secondary neutrons by a track etch
      detector stack. The system was calibrated at high-energy particle accelerators
      and neutron generators. The developed detectors were investigated by an image
      analyser, and from the track parameters the linear energy transfer spectra and
      the absorbed dose were determined (26 microGy/d). Also, the neutron flux was
      estimated below 5 MeV and found to be 2.4 cm(-2) s(-1) directly from the space.
      The construction of the stack allowed to investigate the neutrons also from the
      direction of the carrying satellite, where the flux was found somewhat higher.

PMID- 17504747
TI  - Performance of the UAB and the INFN-LNF Bonner sphere spectrometers in quasi
      monoenergetic neutron fields.
AB  - In the framework of collaboration between the Universidad Autonoma de Barcelona
      and the INFN Frascati National Laboratories, an experimental Bonner Sphere
      neutron spectrometry exercise has been performed in the 2.5 MeV and 14.2 MeV
      quasi monoenergetic neutron beams of the ENEA Fast Neutron Generator. The neutron
      spectra at given distances from the accelerator target have been determined,
      taking advantage of the new unfolding FRUIT code, recently developed by the LNF
      group. The results show a good coherence between the two spectrometers, and
      between the measured and simulated data.

PMID- 17504748
TI  - Electronic stopping power of liquid water for protons down to the Bragg peak.
AB  - An improved dielectric response model that accurately represents the recent
      experimental data for liquid water over the whole Bethe surface is used to
      calculate the electronic stopping power of protons (of fixed-charge) in liquid
      water from several MeV down to the Bragg peak region. The results are by
      approximately 20% lower than the ICRU values and earlier studies. A shell
      correction term with a contribution of 15-20% to Bethe's high-energy stopping
      number is obtained. The present work offers a first-principle approach for
      stopping power calculations that overcomes the well-known limitations of Bethe's
      stopping theory, namely, the need for separate determination of the mean
      excitation energy (the I-value) and the shell-corrections. In particular, all
      type of inner-shell effects are built into the model through the kinematically
      restricted integrals over the Bethe surface. The net contribution of higher-order
      corrections is found to be minimal over most of the present range. Thus, within
      the uncertainty of the dielectric model (few %) the present calculations are
      'exact' down to approximately 100 keV.

PMID- 17504749
TI  - Dosimetry with a transportable water calorimeter in neutron, proton and heavy-ion
      radiation fields.
AB  - A compact and transportable water calorimeter has been developed and extensively
      tested in the intensive, collimated neutron field of the PTB. It has been applied
      for absorbed dose to water measurements in the neutron therapy field of the
      University of Essen, in the proton therapy fields of the HMI in Berlin and at the
      iThemba therapy centre near Cape Town, South Africa, as well as in the (12)C-beam
      of the therapy facility at GSI in Darmstadt, Germany. Absolute dosimetry with
      relative standard uncertainties of less than 1.8% was achieved in all radiation
      fields. The results obtained using the water calorimeter are compared with the
      ionisation chamber measurements in the same radiation fields. The heat defect for
      the water in the calorimeter core was determined separately in independent
      measurements by irradiation with different charged particle beams covering a wide
      range of linear energy transfer.

PMID- 17504750
TI  - Contribution of secondary particles to the dose in 12C radiotherapy and other
      heavy ion beams.
AB  - The results of experimental studies performed in a radiotherapy (12)C ion beam
      with a nominal energy of 500 MeV/amu and in (16)O and (56)Fe ion beams with a
      nominal energy of 1 GeV/amu have been described. Linear energy transfer (LET)
      spectra have been established by means of an LET spectrometer based on a
      chemically etched track detector, and the measured results were also compared
      with theoretical calculations obtained using the program Stopping and Range of
      Ions in Matter (SRIM). It was observed that with increasing depth in a beam, the
      LET spectra are shifted towards higher values of LET; one can also observe an
      important widening of the spectra along the range, as well as an increasing
      amount of nuclear reaction products and/or of fragments in the spectra. The
      relative contribution of these secondary particles to the total absorbed dose was
      assessed.

PMID- 17504751
TI  - Neutron production in tissue-like media and shielding materials irradiated with
      high-energy ion beams.
AB  - Secondary neutrons produced in high-energy therapeutic ion beams require special
      attention since they contribute to the dose delivered to patient, both to tumour
      and to the healthy tissues. Moreover, monitoring of neutron production in the
      beam line elements and the patient is of importance for radiation protection
      aspects around ion therapy facility. Monte Carlo simulations of light ion
      transport in the tissue-like media (water, A-150, PMMA) and materials of interest
      for shielding devices (graphite, steel and Pb) were performed using the SHIELD
      HIT and MCNPX codes. The capability of the codes to reproduce the experimental
      data on neutron spectra differential both in energy and angle is demonstrated for
      neutron yield from the thick targets. Both codes show satisfactory agreement with
      the experimental data. The absorbed dose due to neutrons produced in the water
      and A-150 phantoms is calculated for proton (200 MeV) and carbon (390 MeV/u)
      beams. Secondary neutron dose contribution is approximately 0.6% of the total
      dose delivered to the phantoms by proton beam and at the similar level for both
      materials. For carbon beam the neutron dose contribution is approximately 1.0 and
      1.2% for the water and A-150 phantoms, respectively. The neutron ambient dose
      equivalent, H(10), was determined for neutrons leaving different shielding
      materials after irradiation with ions of various energies.

PMID- 17504752
TI  - Monte Carlo neutron doses estimations inside a PET cyclotron vault room.
AB  - Neutron organ equivalent doses, effective doses and dose equivalents received
      inside a positron emission tomography vault room in a maximum credible accident
      have been estimated with the Monte Carlo code MCNPX. While an operator was inside
      the vault room of a Cyclone 18/9 IBA cyclotron, this was producing (18)F with 30
      muA proton current in the target and the operator had to activate a stopped
      emergency device placed on the wall. MC simulation of the cyclotron vault were
      carried out to estimate the organ and tissue equivalent doses in a mathematical
      male mannequin simulating the operator facing the wall on which the emergency
      device is placed. Doses were calculated at two emergency devices for each one of
      the two targets of the cyclotron, which were able to produce (18)F. The maximum
      effective dose in the mannequin was 6.70 Sv/h and the maximum organ equivalent
      dose was 18.47 Sv/h in spleen.

PMID- 17504753
TI  - Role of LRAT on the retinoid isomerase activity and membrane association of
      Rpe65.
AB  - Absorption of a photon by a vertebrate opsin pigment induces 11-cis to all-trans
      isomerization of its retinaldehyde chromophore. Restoration of light sensitivity
      to the bleached opsin requires chemical re-isomerization of the chromophore via
      an enzyme pathway called the visual cycle. The retinoid isomerase in this pathway
      is Rpe65, a membrane-associated protein in the retinal pigment epithelium (RPE)
      with no predicted membrane-spanning segments. It has been suggested that Rpe65 is
      S-palmitoylated by lecithin:retinol acyl transferase (LRAT) on Cys(231),
      Cys(329), and Cys(330), and that this palmitoylation is required for isomerase
      activity and the association of Rpe65 with membranes. Here we show that the
      affinity of Rpe65 for membranes is similar in wild-type and lrat(-/-) mice. The
      isomerase activity of Rpe65 is also similar in both strains when all-trans
      retinyl palmitate is used as substrate. With all-trans-retinol substrate,
      isomerase activity is present in wild-type but undetectable in RPE homogenates
      from lrat(-/-) mice. Substitution of Cys(231), Cys(329), and Cys(330) with Ser or
      Ala did not affect the affinity of Rpe65 for membranes. Further, these Cys
      residues are not palmitoylated in Rpe65 by mass spectrometric analysis. Global
      inhibition of protein palmitoylation by 2-bromopalmitate did not affect the
      solubility or isomerase activity of Rpe65. Finally, we show that soluble and
      membrane-associated Rpe65 possesses similar isomerase specific activities. These
      results indicate that LRAT is not required for isomerase activity beyond
      synthesis of retinyl-ester substrate, and that the association of Rpe65 with
      membranes is neither dependent upon LRAT nor the result of S-palmitoylation. The
      affinity of Rpe65 for membranes is probably an intrinsic feature of this protein.

PMID- 17504754
TI  - Mast cell-restricted tryptases: structure and function in inflammation and
      pathogen defense.
AB  - Mast cells (MCs) are highly specialized immune cells present in mammals and in
      lower organisms that predate the development of adaptive immunity. The strong
      evolutionary pressure to retain MCs for >500 million years suggests critical
      roles for these cells in our survival. In support of this conclusion, no human
      has been identified to date that lacks MCs, despite the adverse roles of MCs in
      systemic anaphylaxis and varied inflammatory disorders. MCs express numerous
      lineage-restricted neutral proteases, and four members of the chromosome 17A3.3
      family of tryptases are preferentially expressed in mouse MCs. The anatomical
      location of MCs at host-environment interfaces has raised the possibility that
      some of these enzymes are evolutionally conserved because they are needed for
      combating infectious organisms. Here we review recent insights into the structure
      and function of MC tryptases in inflammation and host defense against bacteria
      and other infectious organisms.

PMID- 17504755
TI  - Enhanced skeletal muscle contraction with myosin light chain phosphorylation by a
      calmodulin-sensing kinase.
AB  - Repetitive low frequency stimulation results in potentiation of twitch force
      development in fast-twitch skeletal muscle due to myosin regulatory light chain
      (RLC) phosphorylation by Ca(2+)/calmodulin (CaM)-dependent skeletal muscle myosin
      light chain kinase (skMLCK). We generated transgenic mice that express an skMLCK
      CaM biosensor in skeletal muscle to determine whether skMLCK or CaM is limiting
      to twitch force potentiation. Three transgenic mouse lines exhibited up to 22
      fold increases in skMLCK protein expression in fast-twitch extensor digitorum
      longus muscle containing type IIa and IIb fibers, with comparable expressions in
      slow-twitch soleus muscle containing type I and IIa fibers. The high expressing
      lines showed a more rapid RLC phosphorylation and force potentiation in extensor
      digitorum longus muscle with low frequency electrical stimulation. Surprisingly,
      overexpression of skMLCK in soleus muscle did not recapitulate the fast-twitch
      potentiation response despite marked enhancement of both fast-twitch and slow
      twitch RLC phosphorylation. Analysis of calmodulin binding to the biosensor
      showed a frequency-dependent activation to a maximal extent of 60%. Because
      skMLCK transgene expression is 22-fold greater than the wild-type kinase, skMLCK
      rather than calmodulin is normally limiting for RLC phosphorylation and twitch
      force potentiation. The kinase activation rate (10.6 s(-1)) was only 3.6-fold
      slower than the contraction rate, whereas the inactivation rate (2.8 s(-1)) was
      12-fold slower than relaxation. The slower rate of kinase inactivation in vivo
      with repetitive contractions provides a biochemical memory via RLC
      phosphorylation. Importantly, RLC phosphorylation plays a prominent role in
      skeletal muscle force potentiation of fast-twitch type IIb but not type I or IIa
      fibers.

PMID- 17504757
TI  - ATP-binding modes and functionally important interdomain bonds of sarcoplasmic
      reticulum Ca2+-ATPase revealed by mutation of glycine 438, glutamate 439, and
      arginine 678.
AB  - ATP binds to sarcoplasmic reticulum Ca(2+)-ATPase both in a phosphorylating
      (catalytic) mode and in a nonphosphorylating (modulatory) mode, the latter
      leading to acceleration of phosphoenzyme turnover (Ca(2)E(1)P --> E(2)P and E(2)P
      --> E(2) reactions) and Ca(2+) binding (E(2) --> Ca(2)E(1)). In some of the
      Ca(2+)-ATPase crystal structures, Arg(678) and Glu(439) seem to be involved in
      the binding of nucleotide or an associated Mg(2+) ion. We have replaced Arg(678),
      Glu(439), and Gly(438) with alanine to examine their importance for the enzyme
      cycle and the modulatory effects of ATP and MgATP. The results point to the key
      role of Arg(678) in nucleotide binding and to the importance of interdomain bonds
      Glu(439)-Ser(186) and Arg(678)-Asp(203) in stabilizing the E(2)P and E(2)
      intermediates, respectively. Mutation of Arg(678) had conspicuous effects on
      ATP/MgATP binding to the E(1) form and ADP binding to Ca(2)E(1)P, as well as
      ATP/MgATP binding in modulatory modes to E(2)P and E(2), whereas the effects on
      ATP/MgATP acceleration of the Ca(2)E(1)P --> E(2)P transition were small,
      suggesting that the nucleotide that accelerates Ca(2)E(1)P --> E(2)P binds
      differently from that modulating the E(2)P --> E(2) and E(2) --> Ca(2)E(1)
      reactions. Mutation of Glu(439) hardly affected nucleotide binding to E(1),
      Ca(2)E(1)P, and E(2), but it led to disruption of the modulatory effect of ATP on
      E(2)P --> E(2) and acceleration of the latter reaction, indicating that ATP
      normally modulates E(2)P --> E(2) by interfering with the interaction between
      Glu(439) and Ser(186). Gly(438) seems to be important for this interaction as
      well as for nucleotide binding, probably because of its role in formation of the
      helix containing Glu(439) and Thr(441).

PMID- 17504756
TI  - The threonine that carries fucose, but not fucose, is required for Cripto to
      facilitate Nodal signaling.
AB  - Cripto is a membrane-bound co-receptor for Nodal, a member of the transforming
      growth factor-beta superfamily. Mouse embryos lacking either Cripto or Nodal have
      the same lethal phenotype at embryonic day 7.5. Previous studies suggest that O
      fucosylation of the epidermal growth factor-like (EGF) repeat in Cripto is
      essential for the facilitation of Nodal signaling. Substitution of Ala for the
      Thr to which O-fucose is attached led to functional inactivation of both human
      and mouse Cripto. However, embryos null for protein O-fucosyltransferase 1, the
      enzyme that adds O-fucose to EGF repeats, do not exhibit a Cripto null phenotype
      and die at about embryonic day 9.5. This suggested that the loss of O-fucose from
      the EGF repeat may not have led to the inactivation of Cripto in previous
      studies. Here we investigate this hypothesis and show the following: 1) protein O
      fucosyltransferase 1 is indeed the enzyme that adds O-fucose to Cripto; 2)
      Pofut1(-/-) embryonic stem cells behave the same as Pofut1(+/+) embryonic stem
      cells in a Nodal signaling assay; 3) Pofut1(-/-) and Pofut1(+/+) embryoid bodies
      are indistinguishable in their ability to differentiate into cardiomyocytes; and
      4) none of 10 amino acid substitutions at Thr(72), including Ser which acquires O
      fucose, rescues the activity of mouse Cripto in Nodal signaling assays.
      Therefore, the Thr to which O-fucose is linked in Cripto plays a key functional
      role, but O-fucose at Thr(72) is not required for Cripto to function in cell
      based signaling assays or in vivo. By contrast, we show that O-fucose, and not
      the Thr to which it is attached, is required in the ligand-binding domain of
      Notch1 for Notch1 signaling.

PMID- 17504758
TI  - Transcriptional repression by a conserved intronic sequence in the nicotinic
      receptor alpha3 subunit gene.
AB  - The genes encoding the nicotinic acetylcholine receptor alpha3, alpha5, and beta4
      subunits are genomically clustered. These genes are co-expressed in a variety of
      cells in the peripheral and central nervous systems. Their gene products assemble
      in a number of stoichiometries to generate several nicotinic receptor subtypes
      that have distinct pharmacological and physiological properties. Signaling
      through these receptors is critical for a variety of fundamental biological
      processes. Despite their importance, the transcriptional mechanisms underlying
      their coordinated expression remain to be completely elucidated. By using a
      bioinformatics approach, we identified a highly conserved intronic sequence
      within the fifth intron of the alpha3 subunit gene. Reporter gene analysis
      demonstrated that this sequence, termed "alpha3 intron 5," inhibits the
      transcriptional activities of the alpha3 and beta4 subunit gene promoters. This
      repressive activity is position- and orientation-independent. Importantly,
      repression occurs in a cell type-specific manner, being present in cells that do
      not express the receptor genes or expresses them at very low levels.
      Electrophoretic mobility shift assays demonstrate that nuclear proteins
      specifically interact with alpha3 intron 5 at two distinct sites. We propose that
      this intronic repressor element is important for the restricted expression
      patterns of the nicotinic receptor alpha3 and beta4 subunit genes.

PMID- 17504759
TI  - The extremely conserved C-terminal region of Reelin is not necessary for
      secretion but is required for efficient activation of downstream signaling.
AB  - Reelin is a very large secreted glycoprotein essential for correct development of
      the mammalian brain. It is also implicated in higher functions and diseases of
      human brain. However, whether or not secretion of Reelin is regulated and how
      Reelin transmits signals remain largely unknown. Reelin protein is composed of an
      N-terminal F-spondin-like domain, Reelin repeats, and a short and highly basic C
      terminal region (CTR). The primary sequence of CTR is almost completely conserved
      among vertebrates except fishes, indicating its importance. A prevailing idea
      regarding the function of CTR is that it is required for the secretion of Reelin,
      although this remains unproven. Here we aimed to clarify the function of Reelin
      CTR. Neither deleting most of CTR nor replacing CTR with unrelated amino acids
      affected secretion efficiency, indicating that CTR is not absolutely required for
      the secretion of Reelin. We also found that Reelin mutants without CTR were less
      potent in activating the downstream signaling in cortical neurons. Although these
      mutants were able to bind to the Reelin receptor ectodomain as efficiently as
      wild-type Reelin, quite interestingly, their ability to bind to the isolated cell
      membrane bearing Reelin receptors or receptor-expressing cells (including
      cortical neurons) was much weaker than that of wild-type Reelin. Therefore, it is
      concluded that the CTR of Reelin is not essential for its secretion but is
      required for efficient activation of downstream signaling events, presumably via
      binding to an unidentified "co-receptor" molecule(s) on the cell membrane.

PMID- 17504761
TI  - On the oligomeric state of DJ-1 protein and its mutants associated with Parkinson
      Disease. A combined computational and in vitro study.
AB  - Mutations in the DJ-1 protein are present in patients suffering from familial
      Parkinson disease. Here we use computational methods and biological assays to
      investigate the relationship between DJ-1 missense mutations and the protein
      oligomeric state. Molecular dynamics calculations suggest that: (i) the structure
      of DJ-1 wild type (WT) in aqueous solution, in both oxidized and reduced forms,
      is similar to the crystal structure of the reduced form; (ii) the Parkinson
      disease-causing M26I variant is structurally similar to the WT, consistent with
      the experimental evidence showing the protein is a dimer as WT; (iii) R98Q is
      structurally similar to the WT, consistent with the fact that this is a
      physiological variant; and (iv) the L166P monomer rapidly evolves toward a
      conformation significantly different from WT, suggesting a change in its ability
      to oligomerize. Our combined computational and experimental approach is next used
      to identify a mutant (R28A) that, in contrast to L166P, destabilizes the dimer
      subunit-subunit interface without significantly changing secondary structure
      elements.

PMID- 17504760
TI  - Sodium-dependent extracellular accessibility of Lys-84 in the
      sodium/dicarboxylate cotransporter.
AB  - The Na(+)/dicarboxylate cotransporter transports Na(+) with citric acid cycle
      intermediates such as succinate and citrate. The present study focuses on
      transmembrane helix 3, which is highly conserved among the members of the SLC13
      family. Fifteen amino acids in the extracellular half of transmembrane helix
      (amino acids 98-112) as well as Lys-84, previously shown to affect substrate
      affinity, were mutated individually to cysteine and expressed in the human
      retinal pigment epithelial cell line. Transport specificity ratio analysis shows
      that determinants for distinguishing succinate and citrate are found at amino
      acids Lys-84, Glu-101, Trp-103, His-106, and Leu-111. All of the mutants were
      tested for sensitivity to the membrane-impermeant cysteine-specific reagent (2
      sulfonatoethyl) methanethiosulfonate (MTSES), but only K84C was sensitive to
      MTSES inhibition. The sensitivity of K84C to MTSES was greatest in the presence
      of sodium, and the inhibition could be prevented by addition of substrate or
      replacement of sodium, indicating that the accessibility of Lys-84 changes with
      conformational state. The substrate protection of MTSES inhibition of K84C
      appears to occur early in the transport cycle, before the large-scale
      conformational change associated with translocation of substrate. The results
      point to a new location for Lys-84 within the substrate access pore of the
      Na(+)/dicarboxylate cotransporter, either in a transmembrane helix or a reentrant
      loop facing a water-filled pore.

PMID- 17504762
TI  - Mechanism of inhibition of sequestration of protein kinase C alpha/betaII by
      ceramide. Roles of ceramide-activated protein phosphatases and
      phosphorylation/dephosphorylation of protein kinase C alpha/betaII on threonine
      638/641.
AB  - Sustained activation of protein kinase C (PKC) isoenzymes alpha and betaII leads
      to their translocation to a perinuclear region and to the formation of the
      pericentrion, a PKC-dependent subset of recycling endosomes. In MCF-7 human
      breast cancer cells, the action of the PKC activator 4beta-phorbol-12-myristate
      13-acetate (PMA) evokes ceramide formation, which in turn prevents
      PKCalpha/betaII translocation to the pericentrion. In this study we investigated
      the mechanisms by which ceramide negatively regulates this translocation of
      PKCalpha/betaII. Upon PMA treatment, HEK-293 cells displayed dual phosphorylation
      of PKCalpha/betaII at carboxyl-terminal sites (Thr-638/641 and Ser-657/660),
      whereas in MCF-7 cells PKCalpha/betaII were phosphorylated at Ser-657/660 but not
      Thr-638/641. Inhibition of ceramide synthesis by fumonisin B1 overcame the defect
      in PKC phosphorylation and restored translocation of PKCalpha/betaII to the
      pericentrion. To determine the involvement of ceramide-activated protein
      phosphatases in PKC regulation, we employed small interference RNA to silence
      individual Ser/Thr protein phosphatases. Knockdown of isoforms alpha or beta of
      the catalytic subunits of protein phosphatase 1 not only increased
      phosphorylation of PKCalpha/betaII at Thr-638/641 but also restored PKCbetaII
      translocation to the pericentrion. Mutagenesis approaches in HEK-293 cells
      revealed that mutation of either Thr-641 or Ser-660 to Ala in PKCbetaII abolished
      sequestration of PKC, implying the indispensable roles of phosphorylation of
      PKCalpha/betaII at those sites for their translocation to the pericentrion.
      Reciprocally, a point mutation of Thr-641 to Glu, which mimics phosphorylation,
      in PKCbetaII overcame the inhibitory effects of ceramide on PKC translocation in
      PMA-stimulated MCF-7 cells. Therefore, the results demonstrate a novel role for
      carboxyl-terminal phosphorylation of PKCalpha/betaII in the translocation of PKC
      to the pericentrion, and they disclose specific regulation of PKC
      autophosphorylation by ceramide through the activation of specific isoforms of
      protein phosphatase 1.

PMID- 17504763
TI  - Sequential regulation of diacylglycerol acyltransferase 2 expression by
      CAAT/enhancer-binding protein beta (C/EBPbeta) and C/EBPalpha during
      adipogenesis.
AB  - Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of
      triacylglycerol (TG) synthesis. Despite the existence of an alternative
      acyltransferase (DGAT1), mice lacking DGAT2 have a severe deficiency of TG in
      adipose tissue, indicating a nonredundant role for this enzyme in adipocyte TG
      synthesis. We have studied the regulation of DGAT2 expression during
      adipogenesis. In both isolated murine preadipocytes and 3T3-L1 cells the temporal
      pattern of DGAT2 expression closely mimicked that of genes whose expression is
      regulated by CAAT/enhancer-binding protein beta (C/EBPbeta). Inhibition of
      C/EBPbeta expression in differentiating preadipocytes reduced DGAT2 expression,
      and electrophoretic mobility shift assay and chromatin immunoprecipitation
      experiments identified a promoter element in the DGAT2 gene that is likely to
      mediate this effect. The importance of C/EBPbeta in adipocyte expression of DGAT2
      was confirmed by the finding of reduced DGAT2 expression in the adipose tissue of
      C/EBPbeta-null animals. However, DGAT2 expression is maintained at high levels
      during the later stages of adipogenesis, when C/EBPbeta levels decline. We show
      that, at these later stages of differentiation, C/EBPalpha is capable of
      substituting for C/EBPbeta at the same promoter element. These observations
      provide novel insight into the transcriptional regulation of DGAT2 expression.
      Moreover, they further refine the complex and serial roles of the C/EBP family of
      transcription factors in inducing and maintaining the metabolic properties of
      mature adipocytes.

PMID- 17504764
TI  - Requirement of oxidation-dependent CD40 homodimers for CD154/CD40 bidirectional
      signaling.
AB  - It is well established that the CD154/CD40 interaction is required for T cell
      dependent B cell differentiation and maturation. However, the early molecular and
      structural mechanisms that orchestrate CD154 and CD40 signaling at the T cell/APC
      contact site are not well understood. We demonstrated that CD40 engagement
      induces the formation of disulfide-linked (dl) CD40 homodimers that predominantly
      associate with detergent-resistant membrane microdomains. Mutagenesis and
      biochemical analyses revealed that (a) the integrity of the detergent-resistant
      membranes is necessary for dl-CD40 homodimer formation, (b) the cytoplasmic
      Cys(238) of CD40 is the target for the de novo disulfide oxidation induced by
      receptor oligomerization, and (c) dl-CD40 homodimer formation is required for
      CD40-induced interleukin-8 secretion. Stimulation of CD154-positive T cells with
      staphylococcal enterotoxin E superantigen that mimics nominal antigen in
      initiating cognate T cell/APC interaction revealed that dl-CD40 homodimer
      formation is required for interleukin-2 production by T cells. These findings
      indicate that dl-CD40 homodimer formation has a physiological role in regulating
      bidirectional signaling.

PMID- 17504765
TI  - Functional genomic studies of uropathogenic Escherichia coli and host urothelial
      cells when intracellular bacterial communities are assembled.
AB  - Uropathogenic Escherichia coli (UPEC), the principal cause of urinary tract
      infection in women, colonizes the gut as well as the genitourinary tract. Studies
      of mice inoculated with UTI89, a sequenced isolate, have revealed a complex life
      cycle that includes formation of intracellular bacterial communities (IBCs) in
      bladder urothelial cells. To understand how UPEC adapts to life in IBCs, we have
      used GeneChips and/or quantitative reverse transcriptase PCR to study UTI89
      recovered from the distal gut of gnotobiotic mice and from IBCs harvested by
      laser capture microdissection from the bladder urothelium of infected C3H/HeJ
      female mice. Host responses were characterized in laser capture microdissected
      urothelial cells that do or do not contain IBCs. The results reveal components of
      ferric iron acquisition systems in UTI89 that are expressed at significantly
      higher levels in IBCs compared with the intestine, including the hemin receptor
      chuA (1,390 +/- 188-fold). Localized urothelial responses to IBCs help oppose
      bacterial salvage of host cell iron (e.g. up-regulation of Tfrc (transferrin
      receptor) and Lcn2 (lipocalin 2)), facilitate glucose import (e.g. Hk2
      (hexokinase 2)), and maintain epithelial structural integrity (e.g. Ivl
      (involucrin) and Sbsn (suprabasin)). DeltachuA mutants produce significantly
      smaller IBCs compared with wild type UTI89. This difference was not observed in
      strains lacking sitA (ABC-type iron/manganese transporter subunit), iroN
      (salmochelin receptor), hlyA (alpha-hemolysin), or entF (enterobactin synthetase
      subunit). Together, these studies indicate that heme- and siderophore-associated
      iron play key roles in IBC development and provide a series of microbial and host
      biomarkers for comparing UPEC strains isolated from humans.

PMID- 17504766
TI  - Nucleic acid unwinding by hepatitis C virus and bacteriophage t7 helicases is
      sensitive to base pair stability.
AB  - Helicases are motor enzymes that convert the chemical energy of NTP hydrolysis
      into mechanical force for motion and nucleic acid strand separation. Within the
      cell, helicases process a range of nucleic acid sequences. It is not known
      whether this composite rate of moving and opening the strands of nucleic acids
      depends on the base sequence. Our presteady state kinetic studies of helicases
      from two classes, the ring-shaped T7 helicase and two forms of non-ring-shaped
      hepatitis C virus (HCV) helicase, show that both the unwinding rate and
      processivity depend on the sequence and decrease as the nucleic acid stability
      increases. The DNA unwinding activity of T7 helicase and the RNA unwinding
      activity of HCV helicases decrease steeply with increasing base pair stability.
      On the other hand, the DNA unwinding activity of HCV helicases is less sensitive
      to base pair stability. These results predict that helicases will fall into a
      spectrum of modest to high sensitivity to base pair stability depending on their
      biological role in the cell. Modeling of the dependence provided the degree of
      the active involvement of helicase in base pair destabilization during the
      unwinding process and distinguished between passive and active mechanisms of
      unwinding.

PMID- 17504767
TI  - Medicare Advantage in 2006-2007: what Congress intended?
AB  - Starting in 2006, almost all Medicare beneficiaries have at least one Medicare
      Advantage (MA) plan available to them. Although new regional preferred provider
      organization (R-PPO) plans authorized through the Medicare Prescription Drug,
      Improvement, and Modernization Act (MMA) of 2003 contribute to this growth,
      private fee-for-service (PFFS) plans are more numerous and more popular with
      beneficiaries. Almost 1.5 million beneficiaries are in PFFS plans, 84 percent
      living in "floor" counties paid more by Medicare to encourage MA offerings.
      Whether beneficiaries are well served by policies that use scarce resources to
      encourage competition among largely unmanaged FFS plans is an issue that warrants
      discussion.

PMID- 17504768
TI  - Concurrent exposure to perfluorooctane sulfonate and restraint stress during
      pregnancy in mice: effects on postnatal development and behavior of the
      offspring.
AB  - The combined effects of maternal restraint stress and perfluorooctane sulfonate
      (PFOS) on postnatal development and behavior of the offspring were assessed in
      mice. Thirty-four plug positive females were randomly divided into two groups.
      Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One
      half of the animals in each group was subjected to restraint stress (30 min per
      session, three sessions per day) during the same period. Neither restraint nor
      PFOS exposure significantly modified maternal food or water consumption. Pups of
      dams exposed to 6 mg/kg of PFOS showed a reduced body weight on postnatal days 4
      and 8. Moreover, PFOS exposure induced some delay in developmental landmarks and
      neuromotor maturation. Maternal restraint stress reduced activity in an open
      field when combined with 6 mg PFOS/kg/day. In addition, in males prenatal
      restraint stress impaired motor coordination in a rotarod. The current results
      indicate that concurrent exposure to PFOS and restraint stress during pregnancy
      induces opposite effects on developmental parameters in the pups. These effects
      consist in a general delayed maturation trend induced by PFOS exposure, and a
      general accelerated maturation pattern induced by prenatal stress. Interactive
      effects between PFOS and maternal stress were observed in young adult mice. These
      effects consisted mainly in a diminished activity in an open-field test.

PMID- 17504769
TI  - Comparison of acute neurobehavioral and cholinesterase inhibitory effects of N
      methylcarbamates in rat.
AB  - While the cholinesterase-inhibiting N-methyl carbamate pesticides have been
      widely used, there are few studies evaluating direct functional and biochemical
      consequences of exposure. In the present study of the acute toxicity of seven N
      methyl carbamate pesticides, we evaluated the dose-response profiles of
      cholinesterase (ChE) inhibition in brain and erythrocytes (RBCs) as well as motor
      activity (both horizontally and vertically directed) and clinical signs of overt
      toxicity. The chemicals tested were carbaryl, carbofuran, formetanate,
      methiocarb, methomyl, oxamyl, and propoxur. All were administered orally, and
      rats were tested in 20-min activity sessions beginning 15 min after dosing;
      tissues were collected immediately after activity sessions. In general, motor
      activity was a sensitive measure of ChE inhibition for all these carbamate
      pesticides, and vertical activity showed the greatest magnitude of effect at the
      highest doses compared to either horizontal activity or ChE inhibition. Brain and
      RBC ChE activities were generally affected similarly. Pearson correlation
      coefficients of within-subject data showed good correlation between the
      behavioral and biochemical end points, with brain ChE inhibition and horizontal
      activity showing the highest correlation values. Determination of benchmark dose
      levels for 10% change in each end point also revealed that these two measures
      produced the lowest estimates. Thus, motor activity decreases are highly
      predictive of ChE inhibition for N-methyl carbamates, and vice versa.

PMID- 17504770
TI  - A calcium-binding protein, calbindin-D9k, is regulated through an estrogen
      receptor mediated mechanism following xenoestrogen exposure in the GH3 cell line.
AB  - A variety of environmental chemicals may possess the potential to interact with
      various endocrine factors and consequently cause adverse effects on the
      reproductive, central nervous, and immune systems via the endocrine system(s). In
      this study, we used the GH3 cell line as an in vitro model to determine the
      effects of potential endocrine disruptors (EDs) on the induction of calbindin-D9k
      (CaBP-9k), a useful biomarker for detecting the estrogenic activities of EDs. A
      rat pituitary cell line, GH3, was treated with octyl-phenol (OP), nonyl-phenol
      (NP), and bisphenol A (BPA) in a dose-dependent manner (10(-5), 10(-6), and 10(
      7)M) for 24 h. To determine the time dependency, the cells were exposed to a high
      concentration (10(-5)M) of OP, NP, and BPA and harvested at different time points
      (1, 3, 6, 12, and 24 h). An antiestrogen, ICI 182,780, was used to examine the
      potential involvement of the estrogen receptor (ER) in the induction of CaBP-9k
      by EDs via an ER-mediated pathway. Treatment with OP, NP, and BPA induced a
      significant increase in CaBP-9k expression at both the transcriptional and
      translational levels in a dose-dependent manner. Interestingly, ED exposure
      caused a significant increase in CaBP-9k messenger RNA (mRNA) expression at 6 h,
      whereas induction of CaBP-9k protein was observed as early as 1 h after
      treatment. However, both CaBP-9k mRNA and protein expression peaked at 24 h
      following treatment. The differential response of CaBP-9k mRNA and protein to EDs
      may be explained by translational efficiency. Cotreatment with ICI 182,780
      significantly reversed ED-induced CaBP-9k expression in GH3 cells, suggesting
      that EDs may trigger the induction of CaBP-9k via an ER-mediated pathway in these
      cells. Taken together, these results demonstrate for the first time that a single
      in vitro exposure to OP, NP, or BPA results in an increase in CaBP-9k expression
      in GH3 cells, after 24 h. These results may contribute to our understanding of
      the relationship between the molecular events evoked by ED exposure and its
      biological effects on the pituitary gland in humans and animals. This in vitro
      model, in combination with a single injection in vivo method developed by us, may
      be important for elucidating additional details of the mode of action of
      xenoestrogens and may provide reliable tests for screening estrogenic agonists
      and antagonists.

PMID- 17504771
TI  - An age-dependent physiologically based pharmacokinetic/pharmacodynamic model for
      the organophosphorus insecticide chlorpyrifos in the preweanling rat.
AB  - Juvenile rats are more susceptible than adults to the acute toxicity of
      organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent
      differences in metabolism may be responsible. Of importance are CYP450 activation
      and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol
      (TCP), as well as B-esterase (B-est) and PON-1 (A-esterase) detoxification of CPF
      oxon to TCP. In the current study, a physiologically based
      pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent
      changes in CYP450, PON-1, and tissue B-est levels for rats was developed. In this
      model, age was used as a dependent function to estimate body weight which was
      then used to allometrically scale both metabolism and tissue cholinesterase (ChE)
      levels. In addition, age-dependent changes in brain, liver, and fat volumes and
      brain blood flow were obtained from the literature and used in the simulations.
      Model simulations suggest that preweanling rats are particularly sensitive to CPF
      toxicity, with levels of CPF-oxon in blood and brain disproportionately
      increasing, relative to the response in adult rats. This age-dependent nonlinear
      increase in CPF-oxon concentration may potentially result from both the depletion
      of nontarget B-est and a lower PON-1 metabolic capacity in younger animals. The
      PBPK/PD model behaves consistently with the general understanding of CPF
      toxicity, pharmacokinetics, and tissue ChE inhibition in neonatal and adult rats.
      Hence, this model represents an important starting point for developing a
      computational model to assess the neurotoxic potential of environmentally
      relevant organophosphate exposures in infants and children.

PMID- 17504772
TI  - Supertrees disentangle the chimerical origin of eukaryotic genomes.
AB  - Eukaryotes are traditionally considered to be one of the three natural divisions
      of the tree of life and the sister group of the Archaebacteria. However,
      eukaryotic genomes are replete with genes of eubacterial ancestry, and more than
      20 mutually incompatible hypotheses have been proposed to account for eukaryote
      origins. Here we test the predictions of these hypotheses using a novel supertree
      based phylogenetic signal-stripping method, and recover supertrees of life based
      on phylogenies for up to 5,741 single gene families distributed across 185
      genomes. Using our signal-stripping method, we show that there are three distinct
      phylogenetic signals in eukaryotic genomes. In order of strength, these link
      eukaryotes with the Cyanobacteria, the Proteobacteria, and the Thermoplasmatales,
      an archaebacterial (euryarchaeotes) group. These signals correspond to distinct
      symbiotic partners involved in eukaryote evolution: plastids, mitochondria, and
      the elusive host lineage. According to our whole-genome data, eukaryotes are
      hardly the sister group of the Archaebacteria, because up to 83% of eukaryotic
      genes with a prokaryotic homolog have eubacterial, not archaebacterial, origins.
      The results reject all but two of the current hypotheses for the origin of
      eukaryotes: those assuming a sulfur-dependent or hydrogen-dependent syntrophy for
      the origin of mitochondria.

PMID- 17504773
TI  - Peering through the barriers in GPs' explanations for declining to participate in
      research: the role of professional autonomy and the economy of time.
AB  - BACKGROUND: The level of participation in research by GPs is low internationally.
      Previous reports of the reasons why practitioners decline opportunities for
      research participation have tended to recount the barriers that they describe as
      if they are objective accounts. OBJECTIVE: By theoretical sampling of
      practitioners who had declined to participate in a research trial, we sought to
      interpret the functional significance and interrelationship of the barriers that
      they reported. METHODS: Twenty-three GPs who had declined to participate in a
      trial of training to manage medically unexplained symptoms were interviewed and
      their accounts analysed interpretatively. RESULTS: The practitioners described
      general practice and research as alien fields. Research lacked intrinsic,
      clinical or professional value and was linked to evidence-based medicine which
      they rejected as incompatible with person-centered care. Every doctor described a
      lack of time for research, but time was an elastic resource that payment could
      release from the reservoir of their 'own time'. CONCLUSION: The findings should
      inform the design and interpretation of future quantitative surveys to identify
      how common the attitudes that we report are. Doctors with the attitudes of those
      whom we interviewed will not be drawn into research by measures predicated on the
      assumption that it is intrinsically, clinically or professionally valuable. If
      they cannot be convinced of its utility, value could be conferred by payment for
      participation.

PMID- 17504774
TI  - Physical activity and sedentary behaviours of South Asian and white European
      children in inner city secondary schools in the UK.
AB  - BACKGROUND: People of South Asian (SA) origin have an increased risk of premature
      coronary heart disease. In children of SA origin, there is an increased
      prevalence of obesity and evidence of insulin resistance. Risk factors for
      cardiovascular disease in children often persist into adulthood. Low levels of
      physical activity are likely to be linked to the rise in obesity. OBJECTIVE: To
      determine levels of physical activity and sedentary behaviours in secondary
      school pupils in the UK, including comparison of SA and white European (WE)
      children and those with and without a family history of cardiovascular disease.
      METHOD: Questionnaire survey conducted within an action research study in five
      inner city secondary schools serving a predominantly SA population. RESULTS: We
      obtained 3601 responses from 76% of eligible pupils. WE pupils were more likely
      to have walked to and from school compared to SAs. However, overall we identified
      low levels of physical activity and higher levels of inactive behaviours in both
      ethnic groups. Almost half (46%) of respondents spent four or more hours per day
      watching television or videos or playing computer games. An overall low level of
      active behaviour during school breaks was particularly emphasized in girls. We
      found no evidence of an association between physical activity levels and family
      history of cardiovascular disease. CONCLUSIONS: There is an urgent need for those
      with responsibility for young people's health, including parents, schools and
      community health providers, to consider and address the need for effective
      interventions to encourage increased physical activity levels.

PMID- 17504775
TI  - Patterns of pain and consulting behaviour in patients with musculoskeletal
      disorders in rural Crete, Greece.
AB  - BACKGROUND: Musculoskeletal disorders (MSDs) account as a reason for frequent
      consultations in primary care. However, the magnitude of the problem at the GP's
      clinic, the patterns of pain and the consulting behaviour has not been
      sufficiently explored. OBJECTIVES: The aim of this study was to report on
      patterns of pain relevant to MSDs and explore the co-morbidities and consulting
      behaviour in rural primary care settings in Crete. METHODS: Three primary care
      centres (PCCs) of Crete were selected for a study period of 2 weeks. Every
      visitor, aged 20-75 years, regardless of the reason for visiting the facility was
      invited to participate. The Greek version of the general Nordic questionnaire for
      the analysis of musculoskeletal disorders (NMQ) was used for data collection.
      RESULTS: A total of 455 subjects answered the NMQ. Three hundred and seventy-six
      (82.6%) of the study population reported having one or more symptoms during the
      previous year. Low back (56.9%), neck (34.1%), shoulder (29.9%) and knee (27.9%)
      were the commonest sites of pain. In almost half cases (48.6%), the complaints
      about pain were accompanied by activity restrictions. Multivariate statistical
      analysis showed significant correlations with increasing age and female gender (P
      < 0.05). Common chronic conditions were associated with co-morbidities from the
      musculoskeletal system. Only one-third of those who reported MSDs had consulted
      their GPs for the same problems within the previous year. CONCLUSIONS: MSDs are
      highly prevalent among rural population in Crete but fewer patients seek care
      than those who report symptoms.

PMID- 17504776
TI  - Associations of depression and anxiety with gender, age, health-related quality
      of life and symptoms in primary care COPD patients.
AB  - BACKGROUND: Under-diagnosis of anxiety and depression in Chronic Obstructive
      Pulmonary Disease (COPD) patients may have a negative impact on patient quality
      of life and result in disparity between prevalence and the recognition and
      treatment of these symptoms. OBJECTIVE: To reveal associations of depression and
      anxiety with demographic, health-related quality of life and clinical
      characteristics of COPD patients seen in UK primary care. METHODS: Cross
      sectional population-based postal survey of COPD patients comprising the EQ-5D
      visual analogue scale (EQ-5D(VAS)), the COPD symptom control questionnaire, the
      Hospital Anxiety and Depression Scale, the Medical Research Council dyspnea
      index. Demographic and spirometric data were collected from general practice
      records. RESULTS: A total of 170 (57%) patients consented to take part. Data are
      reported on 110 of these patients for whom up-to-date spirometry was available.
      Approximately one in five participants reported 'caseness' for depression (20.8%)
      and one in three reported anxiety (32.7%). Age and high levels of symptoms were
      independent predictors of anxiety and depression, as was the EQ-5D(VAS) of
      depression. CONCLUSIONS: These data suggest that in UK primary care, depressive
      and anxious symptoms in COPD are related to age and high levels of symptoms.
      Depression is also associated with lower patient-reported generic health status.
      The data suggest that assessment and treatment for depression and anxiety should
      be considered for all COPD patients, not just those with more severe clinical
      levels of disease. The potential of the EQ-5D(VAS) as a screening tool for
      anxiety and depression in primary care COPD patients also merits study.

PMID- 17504778
TI  - Circulating chemokine levels and miscarriage.
AB  - Evidence suggests that chemokines, proteins involved in regulation of
      inflammation and immune response, may have a regulatory function in pregnancy.
      The authors hypothesized that circulating levels of chemokines are associated
      with increased risk of miscarriage. Serum samples were obtained from women in the
      Collaborative Perinatal Project cohort who had had a miscarriage (n=439) and
      controls (n=373) matched by gestational age at sample collection. Concentrations
      of interleukin 8, epithelial cell-derived neutrophil-activating peptide (ENA)-78,
      macrophage inhibitory protein (MIP)-1alpha, MIP-1beta, monocyte chemotactic
      protein 1, and RANTES (regulated upon activation, normal T-cell-expressed, and
      secreted) were determined by multiplex assays, and values were standardized using
      the standard deviation among controls. Conditional logistic regression was used
      to model the relation between chemokine levels and risk of miscarriage. In
      multivariable analysis using all available data, the authors did not observe
      significant associations between any of the evaluated chemokines and miscarriage
      risk. In analyses using subsets of the study population based on the collection
      outcome interval, elevated ENA-78 levels were associated with increased risk of
      miscarriage as the collection-outcome interval increased; the adjusted odds ratio
      was 1.25 (95% confidence interval: 1.04, 1.49) for samples collected more than 35
      days prior to pregnancy outcome. The observation regarding ENA-78, which has
      roles in regulation of angiogenesis and leukocyte recruitment, suggests a
      possible role for this chemokine as an early indicator of miscarriage risk.

PMID- 17504779
TI  - Adherence to lipid-lowering therapy and the use of preventive health services: an
      investigation of the healthy user effect.
AB  - Patients who adhere to preventive therapies may be more likely to engage in a
      broad spectrum of behaviors consistent with a healthy lifestyle. Because many of
      these behaviors cannot be measured easily, observational studies of outcomes
      associated with the long-term use of preventive therapies are subject to the so
      called "healthy user bias." To better understand this effect, the authors
      examined the association between adherence to statin therapy and the use of
      preventive health services in a Pennsylvania cohort of 20,783 new users of
      statins between 1996 and 2004. After adjustment for age, gender, and various
      comorbid conditions, patients who filled two or more prescriptions for a statin
      during a 1-year ascertainment period were more likely than patients who filled
      only one prescription to receive prostate-specific antigen tests (hazard ratio
      (HR)=1.57, 95% confidence interval (CI): 1.17, 2.19), fecal occult blood tests
      (HR=1.31, 95% CI: 1.12, 1.53), screening mammograms (HR=1.22, 95% CI: 1.09,
      1.38), influenza vaccinations (HR=1.21, 95% CI: 1.12, 1.31), and pneumococcal
      vaccinations (HR=1.46, 95% CI: 1.17, 1.83) during follow-up. These results
      suggest that patients who adhere to chronic therapies are more likely to seek out
      preventive health services, such as screening tests and vaccinations. Further
      work is needed to identify study design and analysis methods that can be used to
      minimize the healthy user bias in studies of preventive therapies.

PMID- 17504780
TI  - On the estimation and use of propensity scores in case-control and case-cohort
      studies.
AB  - The use of propensity scores to adjust for measured confounding factors has
      become increasingly popular in cohort studies. However, their use in case-control
      and case-cohort studies has received little attention. The authors present some
      theory on the estimation and use of propensity scores in case-control and case
      cohort studies and present the results of simulation studies that examine whether
      large-sample expectations are realized in studies of typical size. The
      application of propensity scores is less straightforward in case-control and case
      cohort studies than in cohort studies. The authors' simulations revealed two
      potentially important issues. First, when using several potential approaches,
      there is artifactual effect modification of the odds ratio by level of propensity
      score. The magnitude of this phenomenon decreases as the sample size increases.
      Second, several potential approaches produce estimated propensity scores that do
      not converge to the true value as sample size increases and, thus, can fail to
      adjust fully for measured confounding factors. However, the magnitude of residual
      confounding appeared modest in our simulations. Researchers considering using
      propensity scores in case-control or case-cohort studies should consider the
      potential for artifactual effect modification and their reduced ability to
      control for potential confounding factors.

PMID- 17504777
TI  - Toward a model of memory enhancement in schizophrenia: glucose administration and
      hippocampal function.
AB  - Recognition of the need to treat cognitive deficits in schizophrenia is
      compelling and well established, with empirical findings and conceptual arguments
      related to cognitive enhancement appearing regularly in the literature. Cognitive
      enhancement itself, however, remains at an early stage. Biological approaches
      have centered on the development of antipsychotic medications that also improve
      cognition, but the results have so far remained modest. As a way to facilitate
      the development of cognitive enhancers in schizophrenia, this article focuses on
      adjunctive pharmacological approaches to antipsychotic medications and highlights
      the need for systematic explorations of relevant brain mechanisms. While numerous
      conceptual criteria might be employed to guide the search, we will focus on 4
      points that are especially likely to be useful and which have not yet been
      considered together. First, the discussion will focus on deficits in a particular
      cognitive domain, verbal declarative memory. Second, we will review the current
      status of preclinical and clinical efforts to improve declarative memory using
      antipsychotic medications, which is the main, existing mode of treatment. Third,
      we will examine an example of an adjunctive intervention-glucose administration
      that improves memory in animals and humans, modulates function in brain regions
      related to verbal declarative memory, and is highly amenable to translational
      research. Finally, a heuristic model will be outlined to explore how the
      intervention maps on to the underlying neurobiology of schizophrenia. More
      generally, the discussion underlines the promise of cognitive improvement in
      schizophrenia and the need to approach the issue in a programmatic manner.

PMID- 17504781
TI  - Incidental and intentional flavor memory in young and older subjects.
AB  - Incidental and intentional learning and memory for 2 novel flavors were compared
      in young and elderly subjects. Incidental and intentional learning groups rated 2
      new soups on acceptability for different occasions and were tested for memory the
      next day. On the first day, only the intentional group was asked to memorize the
      stimuli. With incidental learning, elderly and young were equally good, but the
      young performed better with intentional than with incidental learning, whereas
      the elderly did not. There were no age-related differences in perceptual
      discrimination. When comparing perceived flavor with the memory of it, the
      elderly tend to overrate intensities of remembered flavor attributes, whereas the
      young tend to underrate them. Memory was not related to flavor pleasantness or
      neophobia. Like memory for taste and texture, flavor memory seems to be mainly
      tuned at detecting changes and based on "feelings of not knowing" rather than on
      precise identification and recognition of previously encountered stimuli.

PMID- 17504782
TI  - The neural bases of the lexical effect: an fMRI investigation.
AB  - The lexical effect is a phenomenon whereby lexical information influences the
      perception of the phonetic category boundary for stimuli from word-nonword
      continua. At issue is whether this effect is due to "top-down" influence of upper
      levels of processing on perceptual processing, or instead is due to decision
      stage processes. In this study, brain activity was monitored using functional
      magnetic resonance imaging as subjects performed a phonetic categorization task
      on items taken from 2 continua in which one end of the continuum was a real word
      and the other was not (gift-kift and giss-kiss). If the lexical effect has a
      perceptual basis, modulation of activation should be seen as a function of the
      lexical effect in areas such as the superior temporal gyri (STG) which have
      previously been implicated in perceptual processing. In contrast, if the effect
      is purely due to decision-related factors, such modulation would be expected only
      in areas which have been linked to executive processes, such as frontal and
      midline structures. Modulation of activation as a function of the lexically
      biased shift in phonetic category boundary was observed in the STG bilaterally as
      well as in frontal and midline structures. This activation pattern suggests that
      the lexical effect has at minimum a perceptual component, in addition to an
      executive decision-related component. These results challenge the view that
      lexical effects on phonetic boundary placement are due solely to postperceptual,
      decision-stage processes, and support those models of language processing which
      allow for higher-level lexical information to directly influence the perception
      of incoming speech.

PMID- 17504783
TI  - Beyond superior temporal cortex: intersubject correlations in narrative speech
      comprehension.
AB  - The role of superior temporal cortex in speech comprehension is well established,
      but the complete network of regions involved in understanding language in
      ecologically valid contexts is less clearly understood. In a functional magnetic
      resonance imaging (fMRI) study, we presented 24 subjects with auditory or
      audiovisual narratives, and used model-free intersubject correlational analyses
      to reveal brain areas that were modulated in a consistent way across subjects
      during the narratives. Conventional comparisons to a resting state were also
      performed. Both analyses showed the expected recruitment of superior temporal
      areas, however, the intersubject correlational analyses also revealed an extended
      network of areas involved in narrative speech comprehension. Two findings stand
      out in particular. Firstly, many areas in the "default mode" network (typically
      deactivated relative to rest) were systematically modulated by the time-varying
      properties of the auditory or audiovisual input. These areas included the
      anterior cingulate and adjacent medial frontal cortex, and the posterior
      cingulate and adjacent precuneus. Secondly, extensive bilateral inferior frontal
      and premotor regions were implicated in auditory as well as audiovisual language
      comprehension. This extended network of regions may be important for higher-level
      linguistic processes, and interfaces with extralinguistic cognitive, affective,
      and interpersonal systems.

PMID- 17504784
TI  - Judicial review: low-priority treatment and exceptional case review.

PMID- 17504785
TI  - Deleterious effects of short-term, high-intensity exercise on immune function:
      evidence from leucocyte mitochondrial alterations and apoptosis.
AB  - BACKGROUND: Although moderate exercise can benefit health, acute and vigorous
      exercise may have the opposite effect. Strenuous exercise can induce alterations
      in the physiology and viability of circulating leucocytes, which have a causal
      relationship with exercise-induced immune distress. OBJECTIVES: To investigate
      the use of mitochondrial transmembrane potential (MTP), a functional marker of
      the energy and viability status of leucocytes, for monitoring the
      immunomodulating effects of short-term, high-intensity exercise. METHODS: 12
      healthy volunteers with a mean Vo(2)max of 70.4 ml/kg/min carried out 3
      consecutive days of high-intensity exercise (85% of Vo(2)max for 30 min every
      day). Blood samples were collected at multiple time points immediately before and
      after each exercise session and at 24 and 72 h after the completion of exercise.
      Leucocyte MTP, apoptosis and circulatory inflammation markers were measured by
      flow cytometry and enzyme-linked immunosorbent assays. RESULTS: MTP of peripheral
      blood leucocytes had declined immediately after the first exercise session and
      remained subnormal 24 h later. It did not normalise until 72 h after exercise.
      The sequential changes in MTP were consistent among the three leucocyte
      subpopulations (polymorphonuclear neutrophils, lymphocytes and monocytes) and
      were significant (p<0.05). Leucocytes displayed a gradual and incremental change
      in their propensity for apoptosis during and after exercise. Similarly, plasma
      concentrations of tumour necrosis factor-alpha and soluble Fas ligand were raised
      during the exercise sessions and had not normalised by 72 h after the completion
      of exercise. Correlation between changes in leucocyte MTP and plasma
      concentrations of tumour necrosis factor-alpha and soluble Fas ligand was
      variable, but significant for polymorphonuclear neutrophils and lymphocytes
      (p<0.05). CONCLUSIONS: Short-term, high-intensity exercise can lead to a
      significant and prolonged dysfunction of the mitochondrial energy status of
      peripheral blood leucocytes, which is accompanied by an increased propensity for
      apoptosis and raised pro-inflammatory mediators. These results support the
      immunosuppressive effects of excessive exercise and suggest that MTP is a useful
      marker of these effects.

PMID- 17504786
TI  - Association of ground hardness with injuries in rugby union.
AB  - BACKGROUND: Ground hardness is considered one of the possible risk factors
      associated with rugby injuries. OBJECTIVES: To examine the contribution of ground
      hardness, rainfall and evapotranspiration to the incidence of injury, and to
      investigate seasonal injury bias throughout one full season of rugby union.
      METHODS: A prospective epidemiological study of rugby injuries was performed on
      271 players from rugby union teams involved in the premier grade rugby
      competition in Dunedin, New Zealand. Ground hardness was measured before each
      match over 20 rounds with an industrial penetrometer, and local weather
      information was collected through the National Institute of Weather and
      Atmospheric Research and the Otago Regional Council. Poisson mixed models were
      used to describe injury incidence as a function of ground hardness throughout the
      season. RESULTS: The overall injury incidence during the season was 52 injuries
      per 1000 match player-hours (95% CI 42 to 65). Although injury incidence
      decreased gradually by round with a rate ratio of 0.98 (95% CI 0.96 to 0.99) (p =
      0.036), and the hardness of match grounds decreased significantly over the season
      (0.16 MPa/round, 95% CI 0.12 to 0.21, p<0.001), a non-significant association was
      demonstrated between injury incidence and ground hardness. Injury incidence was
      not associated with a combination of ground hardness, rainfall and
      evapotranspiration on the day of the match or cumulative rainfall and
      evapotranspiration before each match. CONCLUSIONS: Seasonal change in ground
      hardness and an early-season bias of injuries was demonstrated. Although the
      contribution of ground hardness to injury incidence was not statistically
      significant, match round and injury incidence were highly correlated, confirming
      a seasonal bias, which may confound the relationship of injury to ground
      condition.

PMID- 17504787
TI  - Issues in training the female player.
AB  - On the surface, the women's game appears to be similar to the men's game. On
      closer examination, there are subtle differences in the nature of how each gender
      plays the game, which are evident in the disparity between skills, tactics and
      fitness. The technical weaknesses of women include the first touch, dribbling,
      long passing and goal keeping. These skill limitations have dictated specific
      tactical approaches towards both attack and defence. Specific biological
      limitations inherent in the female player affect the pace and total work output
      in the women's game. Although it is unrealistic to expect the women's game to
      approach the work output of the men's game, specific training of skills and
      fitness will influence the tactical approach to the game.

PMID- 17504788
TI  - Health benefits of tennis.
AB  - The aim of the study was to explore the role of tennis in the promotion of health
      and prevention of disease. The focus was on risk factors and diseases related to
      a sedentary lifestyle, including low fitness levels, obesity, hyperlipidaemia,
      hypertension, diabetes mellitus, cardiovascular disease, and osteoporosis. A
      literature search was undertaken to retrieve relevant articles. Structured
      computer searches of PubMed, Embase, and CINAHL were undertaken, along with hand
      searching of key journals and reference lists to locate relevant studies
      published up to March 2007. These had to be cohort studies (of either cross
      sectional or longitudinal design), case-control studies, or experimental studies.
      Twenty four studies were identified that dealt with physical fitness of tennis
      players, including 17 on intensity of play and 16 on maximum oxygen uptake; 17
      investigated the relation between tennis and (risk factors for) cardiovascular
      disease; and 22 examined the effect of tennis on bone health. People who choose
      to play tennis appear to have significant health benefits, including improved
      aerobic fitness, a lower body fat percentage, a more favourable lipid profile,
      reduced risk for developing cardiovascular disease, and improved bone health.

PMID- 17504789
TI  - The energy expenditure of using a "walk-and-work" desk for office workers with
      obesity.
AB  - OBJECTIVE: For many people, most of the working day is spent sitting in front of
      a computer screen. Approaches for obesity treatment and prevention are being
      sought to increase workplace physical activity because low levels of physical
      activity are associated with obesity. Our hypothesis was that a vertical
      workstation that allows an obese individual to work while walking would be
      associated with significant and substantial increases in energy expenditure over
      seated work. METHODS: The vertical workstation is a workstation that allows an
      office worker to use a standard personal computer while walking on a treadmill at
      a self-selected velocity. 15 sedentary individuals with obesity (14 women, one
      man; 43 (7.5) years, 86 (9.6) kg; body mass index 32 (2.6) kg/m(2)) underwent
      measurements of energy expenditure at rest, seated working in an office chair,
      standing and while walking at a self-selected speed using the vertical
      workstation. Body composition was measured using dual x ray absorptiometry.
      RESULTS: The mean (SD) energy expenditure while seated at work in an office chair
      was 72 (10) kcal/h, whereas the energy expenditure while walking and working at a
      self-selected velocity of 1.1 (0.4) mph was 191 (29) kcal/h. The mean (SD)
      increase in energy expenditure for walking-and-working over sitting was 119 (25)
      kcal/h. CONCLUSIONS: If sitting computer-time were replaced by walking-and
      working, energy expenditure could increase by 100 kcal/h. Thus, if obese
      individuals were to replace time spent sitting at the computer with walking
      computer time by 2-3 h/day, and if other components of energy balance were
      constant, a weight loss of 20-30 kg/year could occur.

PMID- 17504790
TI  - Diagnostic scope of and exposure to primary care physicians in Australia, New
      Zealand, and the United States: cross sectional analysis of results from three
      national surveys.
AB  - OBJECTIVES: To compare mix of patients, scope of practice, and duration of visit
      in primary care physicians in Australia, New Zealand, and the United States.
      DESIGN: Comparison of three comparable cross sectional surveys performed in 2001
      2. Physicians completed a questionnaire on patients' demographics, diagnoses, and
      duration of visit. SETTING: Primary care practice. PARTICIPANTS: 79,790 office
      visits in Australia, 10,064 in New Zealand, and 25,838 in the US. MAIN OUTCOME
      MEASURES: Diagnostic codes were mapped to the Johns Hopkins expanded diagnostic
      clusters. Scope of practice was defined as the number of expanded diagnostic
      clusters accounting for 75% of all managed problems related to morbidity.
      Exposure to primary care was calculated from duration of visits recorded by the
      physician, and reports on rates of visits to primary care for each country.
      RESULTS: In each country, primary care physicians managed an average of 1.4
      morbidity related problems per visit. In the US, 46 expanded diagnostic clusters
      accounted for 75% of problems managed compared with 52 in Australia, and 57 in
      New Zealand. Correlations in the frequencies of managed health problems between
      countries were high (0.87-0.97 for pairwise comparisons). Though primary care
      visits were longer in the US than in New Zealand and Australia, the per capita
      annual exposure to primary care physicians in the US (29.7 minutes) was about
      half of that in New Zealand (55.5 minutes) and about a third of that in Australia
      (83.4 minutes) because of higher rates of visits to primary care in these
      countries. CONCLUSIONS: Despite differences in the supply and financing of
      primary care across countries, many aspects of the clinical practice of primary
      care physicians are remarkably similar in Australia, New Zealand, and the US.

PMID- 17504792
TI  - Increased airway iron as a potential factor in the persistence of Pseudomonas
      aeruginosa infection in cystic fibrosis.
AB  - Iron availability is critical to many bacteria and increased iron has been
      described in airway secretions in cystic fibrosis (CF). The main aim of the
      present study was to assess the relationship between iron in CF sputum and the
      quantitative bacterial burden. Iron, ferritin and total cell counts (TCC) were
      assessed in sputum samples obtained from 15 clinically stable CF patients
      chronically infected with Pseudomonas aeruginosa. Sputum samples were also
      obtained at the commencement of episodes of acute exacerbation in 10 subjects and
      analyses were repeated in six of these exacerbation cases after i.v. antibiotic
      treatment. The relationship between iron indices and the presence of P.
      aeruginosa, as well as total anaerobic bacterial load, was determined. Sputum was
      also obtained from 10 CF patients with no evidence of infection with P.
      aeruginosa and 11 normal healthy controls. Sputum iron, ferritin and TCC were
      significantly elevated in all CF patients, even in those not infected with P.
      aeruginosa, compared with healthy controls. There was a strong positive
      relationship between sputum iron and P. aeruginosa in clinically stable patients,
      but not in samples obtained during an acute exacerbation. There was no
      relationship between sputum iron and anaerobic bacterial load. Antibiotic
      treatment significantly reduced sputum TCC and anaerobic bacterial load, but not
      iron, ferritin or the presence of P. aeruginosa during an exacerbation. In
      conclusion, the present study suggests that increased airway iron may be
      important to Pseudomonas aeruginosa persistence in cystic fibrosis.

PMID- 17504791
TI  - Ventilator-associated pneumonia due to colistin susceptible-only microorganisms.
AB  - Acinetobacter spp. and Pseudomonas aeruginosa are common pathogens of ventilator
      associated pneumonia (VAP). The presentation and outcome of VAP due to
      Acinetobacter spp. and P. aeruginosa susceptible to carbapenems (Carb-S; imipenem
      and/or meropenem) and to colistin only (Col-S) were compared in the present
      retrospective study in three intensive care units. A total of 61 episodes of VAP
      caused by Acinetobacter spp. or P. aeruginosa were studied, of which 30 isolates
      were Carb-S and 31 were Col-S. Demographics, worsening of renal function and
      mortality were not different. The univariate analysis showed that a later onset
      and a previous episode of VAP, prior antimicrobial therapy for >10 days and
      previous therapy with carbapenems during the present admission were more frequent
      in patients with Col-S strains. On multivariate analysis, prior antimicrobial
      therapy for >10 days and a previous episode of VAP remained significantly
      associated with Col-S VAP. Approximately 41% of the infections caused by Col-S
      isolates, but none of those due to Carb-S isolates, had received prior carbapenem
      therapy. Colistin-susceptible ventilator-associated pneumonia episodes can be
      effectively treated using colistin without significant renal dysfunction. This
      susceptibility pattern could be suspected in patients with a previous ventilator
      associated pneumonia episode or prior antibiotic therapy for >10 days preceding
      the present ventilator-associated pneumonia episode.

PMID- 17504793
TI  - Cost-effectiveness of interferon-gamma release assay testing for the treatment of
      latent tuberculosis.
AB  - The aim of the present study was to assess the cost-effectiveness of the new T
      SPOT.TB assay versus the tuberculin skin test (TST) for screening contacts for
      latent tuberculosis (TB) infection in Switzerland. Health and economic outcomes
      of isoniazid treatment of 20- and 40-yr-old close contacts were compared in a
      Markov model over a 20-yr period following screening with TST only (at three cut
      off values) and T-SPOT.TB alone or in combination with the TST. T-SPOT.TB-based
      treatment was cost-effective at (Euro)11,621 and (Euro)23,692 per life-year
      gained (LYG) in the younger and older age group, respectively. No TST-based
      programmes were cost-effective, except at a 15-mm cut-off in the younger group
      only, where the cost-effectiveness ((Euro)26,451.LYG(-1)) fell just below the
      willingness-to-pay threshold. Combination of the TST with T-SPOT.TB slightly
      reduced the total cost compared with the T-SPOT.TB alone by 4.4 and 5.0% in the
      younger and older groups respectively. The number of contacts treated to avoid
      one case of TB decreased from 50 (95% confidence interval 32-106) with the TST
      (10-mm cut-off) to 18 (95%CI 11-43) if T-SPOT.TB was used. Using T-SPOT.TB alone
      or in combination with the tuberculin skin test for screening of close contacts
      before latent tuberculosis infection treatment is highly cost-effective in
      reducing the disease burden of tuberculosis.

PMID- 17504794
TI  - Results of European post-marketing surveillance of bosentan in pulmonary
      hypertension.
AB  - After the approval of bosentan for the treatment of pulmonary arterial
      hypertension (PAH), European authorities required the introduction of a post
      marketing surveillance system (PMS) to obtain further data on its safety profile.
      A novel, prospective, internet-based PMS was designed, which solicited reports on
      elevated aminotransferases, medical reasons for bosentan discontinuation and
      other serious adverse events requiring hospitalisation. Data captured included
      demographics, PAH aetiology, baseline functional status and concomitant PAH
      specific medications. Safety signals captured included death, hospitalisation,
      serious adverse events, unexpected adverse events and elevated aminotransferases.
      Within 30 months, 4,994 patients were included, representing 79% of patients
      receiving bosentan in Europe. In total, 4,623 patients were naive to treatment;
      of these, 352 had elevated aminotransferases, corresponding to a crude incidence
      of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated
      aminotransferases in 150 (3.2%) bosentan-naive patients. Safety results were
      consistent across subgroups and aetiologies. The novel post-marketing
      surveillance captured targeted safety data ("potential safety signals") from the
      majority of patients and confirmed that the incidence and severity of elevated
      aminotransferase levels in clinical practice was similar to that reported in
      clinical trials. These data complement those from randomised controlled clinical
      trials and provide important additional information on the safety profile of
      bosentan.

PMID- 17504795
TI  - Comparison of incremental and constant load tests of inspiratory muscle endurance
      in COPD.
AB  - The aim of the present study was to determine the relative value of incremental
      and constant load tests in detecting changes in inspiratory muscle endurance
      following high-intensity inspiratory muscle training (H-IMT) in chronic
      obstructive pulmonary disease. In total, 16 subjects (11 males; forced expiratory
      volume in one second (FEV(1)) 37.4+/-12.5%) underwent H-IMT. In addition, 17
      subjects (11 males; FEV(1) 36.5+/-11.5%) underwent sham inspiratory muscle
      training (S-IMT). Training took place three times a week for 8 weeks. Baseline
      and post-training measurements were obtained of maximum threshold pressure
      sustained during an incremental load test (P(th,max)) and time breathing against
      a constant load (t(lim)). Breathing pattern was unconstrained. H-IMT increased
      P(th,max) and t(lim) relative to baseline and to any change seen following S-IMT.
      The effect size for P(th,max) was greater than for t(lim). Post-training tests
      were accompanied by changes in breathing pattern, including decreased duty cycle,
      which may have served to decrease inspiratory work and thereby contribute to the
      increase in P(th,max) and t(lim) in both groups. When assessing inspiratory
      muscle function in chronic obstructive pulmonary disease via tests in which the
      pattern of breathing is unconstrained, the current authors recommend incremental
      load tests be used in preference to constant load tests. However, to attribute
      changes in these tests to improvements in inspiratory muscle endurance, breathing
      pattern should be controlled.

PMID- 17504796
TI  - Modulatory effects of N-acetyl-L-cysteine on human eosinophil apoptosis.
AB  - Eosinophils are oxidant-sensitive cells considered relevant in allergic
      inflammation. The present study aimed to examine the effects of the antioxidant N
      acetyl-L-cysteine (NAC) on constitutive and cytokine-delayed apoptosis in human
      isolated eosinophils. Human eosinophils were purified from the blood of healthy
      donors by a magnetic separation system. Apoptosis and cellular glutathione were
      assessed by cytofluorometric analysis and nuclear factor (NF)-kappaB binding
      activity assessed by electrophoresis mobility shift assay. The rate of
      spontaneous apoptosis of human eosinophils after 24 h culture, as assessed by
      annexin-V-positive staining, was mean+/-sem 48.2+/-1.4%, n = 5. Granulocyte
      macrophage colony-stimulating factor (GM-CSF; 10 ng.mL(-1)) decreased apoptosis
      to 19.4+/-1.8%, n = 5. NAC (5 mM) inhibited spontaneous apoptosis (33.6+/-2.7%, n
      = 5) but augmented apoptosis in the presence of GM-CSF (30.9+/-1.5%, n = 5). NAC
      (5 mM) also increased the rate of apoptosis in the presence of tumour necrosis
      factor (TNF)-alpha (10 ng.mL(-1)) and interleukin-5 (5 ng.mL(-1)). NAC (5 mM)
      increased eosinophil glutathione content. The increase in eosinophil NF-kappaB
      binding activity induced by GM-CSF and TNF-alpha was suppressed by NAC. In
      conclusion, N-acetylcysteine modulates eosinophil apoptosis by inhibiting
      constitutive apoptosis but reversing the survival effect produced by inflammatory
      cytokines in human eosinophils.

PMID- 17504797
TI  - Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion.
AB  - Poly (ADP-ribose) synthase or polymerase (PARS and PARP, respectively) is a
      cytotoxic enzyme which causes cellular damage. Nicotinamide, a compound of
      vitamin B complex, has been reported to exert an inhibitory effect on PARS or
      PARP. The present study tests the effects of nicotinamide on acute lung injury
      and associated alterations following ischaemia/reperfusion (I/R) of the isolated
      perfused rat's lung. I/R increased the lung weight (LW) to body weight ratio, LW
      gain, protein and dye tracer leakage, pulmonary arterial pressure and capillary
      permeability. The insult also increased nitrate/nitrite, methyl guanidine, tumour
      necrosis factor-alpha and interleukin-1beta in lung perfusate, while it decreased
      adenosine triphosphate content with an increase in PARP activity in lung tissue.
      Most of the I/R-induced changes were abrogated by post-treatment (30 min after
      I/R) with nicotinamide (100 mg.kg(-1) body weight). However, the increase in
      pulmonary arterial pressure was enhanced by nicotinamide post-treatment.
      Following I/R, the inducible nitric oxide synthase (iNOS) mRNA expression was
      enhanced. Nicotinamide reduced the iNOS expression. The results suggest that
      nicotinamide exerted a protective effect on the acute lung injury caused by
      ischaemia/reperfusion. The mechanisms may be mediated through the inhibition on
      the poly (adenosine diphosphate-ribose) polymerase activity, inducible nitric
      oxide synthase expression and the subsequent suppression of nitric oxide, free
      radicals and pro-inflammatory cytokines with restoration of adenosine
      triphosphate.

PMID- 17504798
TI  - Effect of tiotropium on sputum and serum inflammatory markers and exacerbations
      in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) patients experiencing frequent
      exacerbations demonstrate increased stable-state airway inflammation. Tiotropium
      has been shown to reduce exacerbation frequency, but its effect on airway
      inflammation is unknown. The aim of the present study was to investigate the
      effect of tiotropium on sputum inflammatory markers and exacerbation frequency.
      Patients (n = 142) were randomised to receive tiotropium or placebo in addition
      to their usual medication for 1 yr. Sputum and serum cytokines were assayed by
      ELISA and exacerbation frequency calculated using a symptom-based diary. There
      was no difference in the area under the curve for sputum interleukin (IL)-6 or
      myeloperoxidase between the groups, but sputum IL-8 level was increased in the
      tiotropium arm. There was no difference between start and end of study in serum
      IL-6 or C-reactive protein level. Tiotropium was associated with a 52% reduction
      in exacerbation frequency (1.17 versus 2.46 exacerbations.yr(-1)). Of patients on
      tiotropium, 43% experienced at least one exacerbation, compared with 64% on
      placebo. The total number of exacerbation days was reduced compared with placebo
      (17.3 versus 34.5 days). Tiotropium reduces exacerbation frequency in chronic
      obstructive pulmonary disease, but this effect does not appear to be due to a
      reduction in airway or systemic inflammation.

PMID- 17504799
TI  - Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a
      pooled analysis.
AB  - Bronchial biopsy specimens from chronic obstructive pulmonary disease (COPD)
      patients demonstrate increased numbers of CD8+ T-lymphocytes, macrophages and, in
      some studies, neutrophils and eosinophils. Smoking cessation affects the rate of
      forced expiratory volume in one second (FEV(1)) decline in COPD, but the effect
      on inflammation is uncertain. Bronchial biopsy inflammatory cell counts were
      compared in current and ex-smokers with COPD. A pooled analysis of subepithelial
      inflammatory cell count data from three bronchial biopsy studies that included
      COPD patients who were either current or ex-smokers was performed. Cell count
      data from 101 subjects, 65 current smokers and 36 ex-smokers, were analysed for
      the following cell types: CD4+ and CD8+ T-lymphocytes, CD68+
      (monocytes/macrophages), neutrophil elastase+ (neutrophils), EG2+ (eosinophils),
      mast cell tryptase+ and cells mRNA-positive for tumour necrosis factor-alpha.
      Current smokers and ex-smokers were similar in terms of lung function, as
      measured by FEV(1) (% predicted), forced vital capacity (FVC) and FEV(1)/FVC. The
      results demonstrate that there were no significant differences between smokers
      and ex-smokers in the numbers of any of the inflammatory cell types or markers
      analysed. It is concluded that, in established chronic obstructive pulmonary
      disease, the bronchial mucosal inflammatory cell infiltrate is similar in ex
      smokers and those that continue to smoke.

PMID- 17504800
TI  - Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung
      fibrosis.
AB  - Epithelial cell injury and apoptosis are recognised as early features in
      idiopathic pulmonary fibrosis and bleomycin-induced fibrosis in mice. Telomerase
      is a known apoptosis-alleviating factor. The role of telomerase was studied
      during bleomycin-induced lung epithelial cell (LEC) apoptosis in vitro in a mouse
      LEC line, and in vivo in LECs isolated from bleomycin-treated mice. The current
      authors evaluated changes in murine telomerase reverse transcriptase (mTERT) mRNA
      levels and changes in telomerase activity with the TRAPeze Detection Kit,
      telomeric length with the TeloTTAGGG Telomere Length Kit, and LEC apoptosis with
      FACScan and 4,6-diamino-2-phenylindole dihydrochloride stain. There was a
      significant elevation in mTERT mRNA and a transient 41% increase in telomerase
      activity 24 h after in vitro bleomycin treatment. At 72 h, telomerase activity
      had fallen to 26% below levels in untreated cells. Reduction of telomerase
      activity over time, or by direct inhibition, significantly elevated LEC
      apoptosis. No change in average telomeric length was noted. In vivo, telomerase
      activity of LECs from bleomycin-treated mice increased at 7 and 14 days. In
      conclusion, telomerase activity may play a protective role against robust
      bleomycin-induced lung epithelial cell apoptosis. Moreover, stabilising
      telomerase activity may decrease epithelial cell apoptosis and the resulting lung
      fibrosis.

PMID- 17504801
TI  - Recurrent tuberculosis from 1992 to 2004 in a metropolitan area.
AB  - The proportion of recurrent tuberculosis (TB) cases caused by re-infection has
      varied widely in previous studies. The aim of the present study was to determine
      the relative frequency of relapse and exogenous re-infection in patients with
      second episodes of TB, using DNA fingerprinting. A population-based retrospective
      longitudinal descriptive study was conducted in Madrid (Spain) during 1992-2004.
      The study consisted of 645 patients with culture-confirmed TB. Of these, 20
      (3.1%) were retained because they presented with a second isolate of
      Mycobacterium tuberculosis. Finally, 12 of these cases were excluded because they
      did not complete the full treatment prescribed. All strains were typed by
      restriction fragment length polymorphism analysis and some by mycobacterial
      interspersed repetitive unit-variable number of tandem repeats analysis. The
      patients with recurrent TB were compared with those without recurrent TB. For
      seven out of the eight patients, the restriction fragment length polymorphism
      patterns of the Mycobacterium tuberculosis strains from the episodes of recurrent
      disease showed identical initial and final genotypes, indicating relapse; the
      remaining recurrent case showed different genotypes, suggesting exogenous re
      infection. Re-infection is possible among people in developed countries, but the
      rates are lower than those occurring in high-risk areas. The risk factors for
      recurrent tuberculosis should be taken into account in the follow-up of treatment
      and tuberculosis control strategies.

PMID- 17504802
TI  - Early and late effects of cardiac resynchronization therapy on exercise-induced
      mitral regurgitation: relationship with left ventricular dyssynchrony,
      remodelling and cardiopulmonary performance.
AB  - AIMS: Exercise-induced mitral regurgitation (MR) bears a poor prognosis in
      patients with congestive heart failure (CHF). Cardiac resynchronization therapy
      (CRT) is associated with improved clinical outcome but its effects on exercise
      induced MR remain undetermined. We investigated serial changes in functional MR
      in relation to left ventricular (LV) remodelling and cardiopulmonary performance
      after CRT. METHODS AND RESULTS: Twenty-eight patients with CHF (LV ejection
      fraction 25 +/- 7%), broad QRS complex (171 +/- 27 ms), and at least mild MR
      [effective regurgitant orifice (ERO) 0.25 +/- 0.12 cm2] were studied with
      quantitative exercise echocardiography and cardiopulmonary exercise testing
      prior, within 1 week, and 3 months after CRT. Early after CRT, a decrease in LV
      dyssynchrony (from 54 +/- 21 to 19 +/- 7 ms, P < 0.001) and in MR at rest (ERO
      from 0.25 +/- 0.12 to 0.20 +/- 0.10 cm2, P = 0.047) was observed. However, no
      change in exercise-induced increase in MR was observed (ERO from 0.34 +/- 0.12 to
      0.31 +/- 0.16 cm2, NS). Three months after CRT, a decrease in the mitral valve
      tenting area (from 3.3 +/- 1.2 to 2.0 +/- 0.6 cm2, P < 0.001) and an increase in
      LV sphericity index (from 1.5 +/- 0.3 to 1.8 +/- 0.5, P < 0.001) were paralleled
      by an attenuation of exercise-induced MR (ERO 0.19 +/- 0.06 cm(2), P = 0.001 vs.
      prior CRT). This was associated with an increase in LV ejection fraction (from 25
      +/- 7 to 35 +/- 9%, P < 0.001), peak oxygen uptake (from 11.7 +/- 2.4 to 13.7 +/-
      3.8 mL/kg/min, P = 0.001), and a decrease in Nt-pro-BNP (from 2777 +/- 1681 to
      1963 +/- 1361 pg/mL, P = 0.067). CONCLUSION: CRT is associated with acute
      decrease in resting MR but does not immediately attenuate exercise-induced MR. In
      contrast, only late, CRT-induced reversed LV remodelling and reduced mitral
      apparatus deformation are associated with a reduction in both resting and
      exercise-induced MR and with an improvement in cardiopulmonary performance.

PMID- 17504803
TI  - Is subendocardial ischaemia present in patients with chest pain and normal
      coronary angiograms? A cardiovascular MR study.
AB  - AIMS: On the basis of an MRI study it has been suggested that subendocardial
      hypoperfusion is present in patients with cardiac syndrome X. However, further
      work is required to test whether these findings can be generalized. METHODS AND
      RESULTS: MRI was used to visually and semi-quantitatively assess subendocardial
      and subepicardial perfusion, at rest and during an infusion of adenosine, in 20
      patients with angina pectoris and normal coronary angiograms. A myocardial
      perfusion index (MPI) was calculated using the normalized upslope of myocardial
      signal enhancement. An index for myocardial perfusion reserve (MPRI) was
      calculated by dividing the MPI values at maximal vasodilatation by the values at
      rest. The MPI in our study population increased significantly during adenosine
      infusion in both the subendocardium (from 0.091 +/- 0.020 to 0.143 +/- 0.030; P <
      0.001) and the subepicardium (from 0.074 +/- 0.017 to 0.135 +/- 0.03; P < 0.001).
      The overall MPRI was 1.83 +/- 0.50. CONCLUSION: The results show that patients
      with chest pain and normal coronary angiograms had significant perfusion
      responses to adenosine in both the subendocardium and subepicardium. In the
      present study we found no evidence for subendocardial hypoperfusion in these
      patients.

PMID- 17504804
TI  - Assessment of the contractile reserve in patients with intermediate coronary
      lesions: a strain rate imaging study validated by invasive myocardial fractional
      flow reserve.
AB  - AIMS: The present study aims to compare the change of left ventricular
      deformation during dobutamine stress echocardiography (DSE) with the reference
      standard of invasive myocardial fractional flow reserve (FFR) to assess the
      haemodynamic significance of intermediate coronary lesions. METHODS AND RESULTS:
      In 30 patients with an intermediate coronary artery stenosis in one epicardial
      coronary artery, FFR measurements were performed during coronary catheterization.
      In case of an FFR < 0.75 after intracoronary adenosine administration, the
      stenosis was considered significant, indicating ischaemia. In addition, during
      DSE, peak systolic strain rate and systolic strain of the region of interest
      (supplied by the stenotic vessel) and of a non-ischaemic remote region were
      assessed at baseline and at peak stress. Thirteen patients had an FFR >or= 0.75,
      indicating normal flow reserve (non-ischaemic group). The remaining 17 patients
      with an FFR < 0.75 comprised the ischaemic group. At baseline DSE, mean values of
      strain rate (-1.2 +/- 0.3 s(-1)) and strain (-17 +/- 8%) were not significantly
      different between both groups. In the ischaemic group, in the target region,
      strain at peak stress decreased to - 10 +/- 8%, whereas strain rate remained
      unchanged. In contrast, in the non-ischaemic group, strain at peak stress
      remained unchanged (-18 +/- 7%), whereas strain rate increased to - 2.5 +/- 1.1
      s(-1). The receiver operating characteristic curve analysis revealed the change
      in strain rate as the best parameter to detect ischaemia, with a sensitivity of
      89% and a specificity of 86%. In the remote region, in both groups, strain rate (
      1.4 +/- 0.4 s(-1)) and strain values (-20 +/- 7%) were not significantly
      different at baseline, and strain rate doubled and strain remained unchanged at
      DSE peak stress. CONCLUSION: Non-invasive evaluation of regional deformation,
      using strain rate imaging during DSE, predicted the relevance of intermediate
      coronary stenosis. In this context, strain rate is superior to strain
      measurements for the quantification of the contractile reserve.

PMID- 17504805
TI  - Inadequate antimicrobial prophylaxis during surgery: a study of beta-lactam
      levels during burn debridement.
AB  - OBJECTIVES: To determine how long single-dose prophylactic antibiotic regimens
      for burns surgery maintained plasma concentrations above the MICs for target
      organisms during surgery. PATIENTS AND METHODS: We monitored antibiotic plasma
      concentrations in 12 patients (mean +/- SD 43 +/- 12% total burn surface area)
      throughout debridement surgery after administration of the standard prophylactic
      antibiotic dosing regimens of either 1 g of intravenous cefalotin or 4.5 g of
      intravenous piperacillin/tazobactam. RESULTS: The eschar debridement and grafting
      procedures ranged in duration from 2.25 to over 8.5 h. The duration of total
      plasma cefalotin concentration above an MIC of 0.2 mg/L for Staphylococcus aureus
      was 6.49 +/- 2.85 h, whereas the mean duration of total plasma piperacillin
      concentration above an MIC of 64 mg/L for Pseudomonas aeruginosa was only 1.15 +/
      0.59 h. None of the patients dosed with piperacillin/tazobactam was adequately
      protected for the duration of their surgery and adequate prophylaxis was only
      evident in four of the nine patients administered cefalotin. CONCLUSIONS: These
      results suggest a need to review antibiotic prophylaxis dosage regimens for burns
      surgery and the adoption of regimens that will minimize the risk of infection in
      this high-risk patient group. It is suggested that the antibiotic prophylaxis
      guideline for burn debridement surgery be modified to include re-dosing or a
      continuous infusion of beta-lactam antibiotics.

PMID- 17504806
TI  - Dynamic cofilin phosphorylation in the control of lamellipodial actin
      homeostasis.
AB  - During animal cell chemotaxis, signalling at the plasma membrane induces actin
      polymerisation to drive forward cell movement. Since the cellular pool of actin
      is limited, efficient protrusion formation also requires the coordinated
      disassembly of pre-existing actin filaments. To search for proteins that can
      monitor filamentous and globular actin levels to maintain the balance of
      polymerisation and disassembly, we followed changes in the proteome induced by
      RNA interference (RNAi)-mediated alterations in actin signalling. This unbiased
      approach revealed an increase in the levels of an inactive, phosphorylated form
      of the actin-severing protein cofilin in cells unable to generate actin-based
      lamellipodia. Conversely, an increase in F-actin levels induced the
      dephosphorylation and activation of cofilin via activation of the Ssh
      phosphatase. Similarly, in the context of acute phosphoinositide 3-kinase (PI3K)
      signalling, dynamic changes in cofilin phosphorylation were found to depend on
      the Ssh phosphatase and on changes in lamellipodial F-actin. These results
      indicate that changes in the extent of cofilin phosphorylation are regulated by
      Ssh in response to changes in the levels and/or organisation of F-actin. Together
      with the recent finding that Ssh phosphatase activity is augmented by F-actin
      binding, these results identify Ssh-dependent regulation of phosphorylated
      cofilin levels as an important feedback control mechanism that maintains actin
      filament homeostasis during actin signalling.

PMID- 17504807
TI  - Cellular prion protein interaction with vitronectin supports axonal growth and is
      compensated by integrins.
AB  - The physiological functions of the cellular prion protein, PrP(C), as a cell
      surface pleiotropic receptor are under debate. We report that PrP(C) interacts
      with vitronectin but not with fibronectin or collagen. The binding sites
      mediating this PrP(C)-vitronectin interaction were mapped to residues 105-119 of
      PrP(C) and the residues 307-320 of vitronectin. The two proteins were co
      localized in embryonic dorsal root ganglia from wild-type mice. Vitronectin
      addition to cultured dorsal root ganglia induced axonal growth, which could be
      mimicked by vitronectin peptide 307-320 and abrogated by anti-PrP(C) antibodies.
      Full-length vitronectin, but not the vitronectin peptide 307-320, induced axonal
      growth of dorsal root neurons from two strains of PrP(C)-null mice. Functional
      assays demonstrated that relative to wild-type cells, PrP(C)-null dorsal root
      neurons were more responsive to the Arg-Gly-Asp peptide (an integrin-binding
      site), and exhibited greater alphavbeta3 activity. Our findings indicate that
      PrP(C) plays an important role in axonal growth, and this function may be rescued
      in PrP(C)-knockout animals by integrin compensatory mechanisms.

PMID- 17504808
TI  - The Clr4 methyltransferase determines the subnuclear localization of the mating
      type region in fission yeast.
AB  - The genome has a non-random spatial distribution in the cell nucleus. In
      Schizosaccharomyces pombe, it has been shown that the centromeres, telomeres and
      the mating-type region localize to the nuclear membrane (NM), the former by
      attaching to the spindle pole body (SPB). In addition, reporter genes inserted
      into these areas are transcriptionally repressed because of the formation of
      specialized chromatin structures. Performing live cell analysis we found that in
      a wild-type strain the mating-type region was positioned in the proximity of the
      SPB, the location where the pericentromeric heterochromatin is also found. In a
      strain lacking the histone methyltransferase Clr4, crucial for the formation of
      heterochromatin, the mating-type region had a random localization in the nucleus.
      Moreover, in a strain in which the two boundary elements IR-L and IR-R had been
      deleted, the mating-type region was displaced from its position at the proximity
      of the SPB, but remained in the vicinity of the NM. Moreover, in all investigated
      strains with silencing deficiencies the distance between the mating-type region
      and the SPB increased. This result indicates a correlation between
      transcriptional derepression and displacement of the region. Two different models
      of how the mating-type chromatin is organized in the nucleus are discussed.

PMID- 17504809
TI  - The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell
      migration.
AB  - Wrch-1 (Wnt-regulated Cdc42 homolog) is a new member of the Rho family that was
      identified as a gene transcriptionally upregulated by Wnt-1. Wrch-1 has no
      detectable GTPase activity and displays very high intrinsic guanine nucleotide
      exchange, implying that it is constitutively GTP-bound. The biological functions
      of Wrch-1 largely remain to be characterized. Here, we report that Wrch-1
      prominently localizes to focal adhesions. Depletion of Wrch-1 by small
      interfering RNA increases focal adhesion formation, whereas Wrch-1 overexpression
      disassembles focal adhesions. Wrch-1 depletion inhibits myosin-light-chain
      phosphorylation, which in turn leads to an increase in the number of focal
      adhesions and inhibits cell migration in response to wound healing. Depletion of
      Wrch-1 also inhibits Akt and JNK activation. Although pharmacological inhibitors
      of Akt and JNK inhibit cell migration, they do not affect focal adhesions. Thus,
      our data suggest that Wrch-1 regulates cell migration by multiple mechanisms: on
      the one hand Wrch-1 controls focal adhesions by regulating myosin light chain and
      on the other hand Wrch-1 stimulates the activation of Akt and JNK.

PMID- 17504810
TI  - Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and
      gamma-secretase-dependent E-cadherin cleavage.
AB  - Enterotoxigenic Bacteroides fragilis - organisms that live in the colon - secrete
      a metalloprotease toxin, B. fragilis toxin. This toxin binds to a specific
      intestinal epithelial cell receptor and stimulates cell proliferation, which is
      dependent, in part, on E-cadherin degradation and beta-catenin-T-cell-factor
      nuclear signaling. Gamma-secretase (or presenilin-1) is an intramembrane cleaving
      protease and is a positive regulator of E-cadherin cleavage and a negative
      regulator of beta-catenin signaling. Here we examine the mechanistic details of
      toxin-initiated E-cadherin cleavage. B. fragilis toxin stimulated shedding of
      cell membrane proteins, including the 80 kDa E-cadherin ectodomain. Shedding of
      this domain required biologically active toxin and was not mediated by MMP-7,
      ADAM10 or ADAM17. Inhibition of gamma-secretase blocked toxin-induced proteolysis
      of the 33 kDa intracellular E-cadherin domain causing cell membrane retention of
      a distinct beta-catenin pool without diminishing toxin-induced cell
      proliferation. Unexpectedly, gamma-secretase positively regulated basal cell
      proliferation dependent on the beta-catenin-T-cell-factor complex. We conclude
      that toxin induces step-wise cleavage of E-cadherin, which is dependent on toxin
      metalloprotease and gamma-secretase. Our results suggest that differentially
      regulated beta-catenin pools associate with the E-cadherin-gamma-secretase
      adherens junction complex; one pool regulated by gamma-secretase is important to
      intestinal epithelial cell homeostasis.

PMID- 17504811
TI  - Inhibition of complex III promotes loss of Ca2+ dependence for mitochondrial
      superoxide formation and permeability transition evoked by peroxynitrite.
AB  - In intact U937 cells, peroxynitrite promotes the mitochondrial formation of
      superoxide via a Ca2+-dependent mechanism involving inhibition of complex III.
      Superoxide then readily dismutates to H2O2 causing lesions on different
      biomolecules, including DNA. Here we show that formation of H2O2 and DNA damage
      are suppressed by inhibition of complex I (by rotenone) or ubisemiquinone
      formation (by myxothiazol), as well as by a variety of manipulations preventing
      either the mobilization of Ca2+ or its mitochondrial accumulation. In addition,
      complex III inhibitors promoted rotenone- or myxothiazol-sensitive formation of
      H2O2 and DNA strand scission in cells exposed to otherwise inactive
      concentrations of peroxynitrite. However, under these conditions, the intra
      mitochondrial concentration of Ca2+ remained unchanged and the effects of
      peroxynitrite therefore take place via Ca2+-independent mechanisms. H2O2
      formation was paralleled by, and causally linked to, the loss of mitochondrial
      membrane potential associated with the mitochondrial release of cytochrome c and
      AIF, and with the mitochondrial accumulation of Bax. These events, although Ca2+
      independent, were rapidly followed by death mediated by mitochondrial
      permeability transition, generally considered a typical Ca2+-dependent event.
      Thus, enforced inhibition of complex III promotes the loss of Ca2+ dependence of
      those mitochondrial mechanisms regulating superoxide formation and mitochondrial
      permeability transition evoked by peroxynitrite.

PMID- 17504812
TI  - Candida albicans hyphal morphogenesis occurs in Sec3p-independent and Sec3p
      dependent phases separated by septin ring formation.
AB  - The growing tips of Candida albicans hyphae are sites of polarized exocytosis.
      Mammalian septins have been implicated in regulating exocytosis and C. albicans
      septins are known to localize at hyphal tips, although their function here is
      unknown. Here, we report that C. albicans cells deleted of the exocyst subunit
      gene SEC3 can grow normal germ tubes, but are unable to maintain tip growth after
      assembly of the first septin ring, resulting in isotropic expansion of the tip.
      Deleting either of the septin genes CDC10 or CDC11 caused Sec3p mislocalization
      and surprisingly, also restored hyphal development in the sec3Delta mutant
      without rescuing the temperature sensitivity. Co-immunoprecipitation experiments
      detected association of the septin Cdc3p with the exocyst subunits Sec3p and
      Sec5p. Our results reveal that C. albicans hyphal development occurs through
      Sec3p-independent and dependent phases, and provide strong genetic and
      biochemical evidence for a role of septins in polarized exocytosis.

PMID- 17504813
TI  - Arabidopsis clock-associated pseudo-response regulators PRR9, PRR7 and PRR5
      coordinately and positively regulate flowering time through the canonical
      CONSTANS-dependent photoperiodic pathway.
AB  - Photoperiodism allows organisms to measure daylength, or external photoperiod,
      and to anticipate coming seasons. Daylength measurement requires the integration
      of light signal and temporal information by the circadian clock. In the long-day
      plant Arabidopsis thaliana, CONSTANS (CO) plays a crucial role in integrating the
      circadian rhythm and environmental light signals into the photoperiodic flowering
      pathway. Nevertheless, the molecular mechanism by which the circadian clock
      modulates the cyclic expression profile of CO is poorly understood. Here, we
      first showed that the clock-associated genes PSEUDO-RESPONSE REGULATOR (PRR)
      PRR9, PRR7 and PRR5 are involved in activation of CO expression during the
      daytime. Then, extensive genetic studies using CIRCADIAN CLOCK-ASSOCIATED1
      (CCA1)/LATE ELONGATED HYPOCOTYL (LHY) double mutants (cca1/lhy) and prr7/prr5
      were conducted. The results suggested that PRR genes act coordinately in a manner
      parallel with and antagonistic to CCA/LHY, upstream of the canonical CO-FLOWERING
      LOCUS T (FT) photoperiodic flowering pathway. Finally, we provided evidence to
      propose a model, in which CCA1/LHY repress CO through GIGANTEA (GI), while PRR9,
      PRR7 and PRR5 activate CO predominantly by repressing CYCLING DOF FACTOR1 (CDF1)
      encoding a DNA-binding transcriptional repressor.

PMID- 17504814
TI  - Xyloglucan endo-transglycosylase (XET) functions in gelatinous layers of tension
      wood fibers in poplar--a glimpse into the mechanism of the balancing act of
      trees.
AB  - Tension wood is a specialized tissue of deciduous trees that functions in bending
      woody stems to optimize their position in space. Tension wood fibers that develop
      on one side of the stem have an increased potency to shrink compared with fibers
      on the opposite side, thus creating a bending moment. It is believed that the
      gelatinous (G) cell wall layer containing almost pure cellulose of tension wood
      fibers is pivotal to their shrinking. By analyzing saccharide composition and
      linkage in isolated G-layers of poplar, we found that they contain some matrix
      components in addition to cellulose, of which xyloglucan is the most abundant.
      Xyloglucan, xyloglucan endo-transglycosylase (XET) activity and xyloglucan endo
      transglycosylase/hydrolase (XTH) gene products were detected in developing G
      layers by labeling using CCRC-M1 monoclonal antibody, in situ incorporation of
      XXXG-SR and the polyclonal antibody to poplar PttXET16-34, respectively,
      indicating that xyloglucan is incorporated into the G-layer during its
      development. Moreover, several XTH transcripts were altered and were generally up
      regulated in developing tension wood compared with normal wood. In mature G
      fibers, XTH gene products were detected in the G-layers while the XET activity
      was evident in the adjacent S(2) wall layer. We propose that XET activity is
      essential for G-fiber shrinking by repairing xyloglucan cross-links between G-
      and S(2)-layers and thus maintaining their contact. Surprisingly, XTH gene
      products and XET activity persisted in mature G-fibers for several years,
      suggesting that the enzyme functions after cell death repairing the cross-links
      as they are being broken during the shrinking process.

PMID- 17504815
TI  - The AtMAP65-1 cross-bridge between microtubules is formed by one dimer.
AB  - The microtubule-associated protein AtMAP65-1 from Arabidopsis thaliana dimerizes
      and forms 25 nm cross-bridges between microtubules, but the exact mechanism is
      unknown. Here, we used the predicted three-dimensional structure of AtMAP65-1 as
      a basis for analyzing the actual cross-bridging in detail. Fold-recognition
      predicts that AtMAP65-1 contains four coiled-coil domains and a flexible extended
      loop. The length of these coiled-coil domains is about 25 nm, suggesting that one
      molecule could span the gap, hence forming an antiparallel overlapping dimer
      instead of an end-to-end dimer. We then tested this model by using truncations of
      AtMAP65-1. EDC {[3-(dimethylamino) propyl] carbodiimide} cross-linking analysis
      indicated that the N-terminus of the rod domain of AtMAP65-1 (amino acids 1-339)
      binds to the C-terminus of the rod domain (amino acids 340-494) and also
      participates in connecting the two antiparallel proteins in the cross-bridge.
      Nevertheless, microtubules can still form bundles in the presence of AtMAP65-1
      340-587 (amino acids 340-587) or AtMAP65-1 1-494 (amino acids 1-494). Comparing
      the cold stability of microtubule bundles induced by full-length AtMAP65-1 with
      that of AtMAP65-1 340-587 or AtMAP65-1 1-494, we conclude that AtMAP65-1 495-587
      acts as a flexible extended loop, playing a crucial role in binding to and
      stabilizing microtubules in the AtMAP65-1 cross-bridge.

PMID- 17504816
TI  - Enzymatic activity and motility of recombinant Arabidopsis myosin XI, MYA1.
AB  - We expressed recombinant Arabidopsis myosin XI (MYA1), in which the motor domain
      of MYA1 was connected to an artificial lever arm composed of triple helical
      repeats of Dictyostelium alpha-actinin, in order to understand its motor activity
      and intracellular function. The V(max) and K(actin) of the actin-activated Mg(2+)
      ATPase activity of the recombinant MYA1 were 50.7 Pi head(-1) s(-1) and 30.2
      microM, respectively, at 25 degrees C. The recombinant MYA1 could translocate
      actin filament at the maximum velocity of 1.8 microm s(-1) at 25 degrees C in the
      in vitro motility assay. The value corresponded to a motility of 3.2 microm s(-1)
      for native MYA1 if we consider the difference in the lever arm length, and this
      value was very close to the velocity of cytoplasmic streaming in Arabidopsis
      hypocotyl epidermal cells. The extent of inhibition by ADP of the motility of
      MYA1 was similar to that of the well-known processive motor, myosin V, suggesting
      that MYA1 is a processive motor. The dissociation rate of the actin-MYA1-ADP
      complex induced by ATP (73.5 s(-1)) and the V(max) value of the actin-activated
      Mg(2+) ATPase activity revealed that MYA1 stays in the actin-bound state for
      about 70% of its mechanochemical cycle time. This high ratio of actin-bound
      states is also a characteristic of processive motors. Our results strongly
      suggest that MYA1 is a processive motor and involved in vesicle transport and/or
      cytoplasmic streaming.

PMID- 17504817
TI  - Worldwide trends in the prevalence of asthma symptoms: phase III of the
      International Study of Asthma and Allergies in Childhood (ISAAC).
AB  - BACKGROUND: Phase I of the International Study of Asthma and Allergies in
      Childhood (ISAAC) was designed to allow worldwide comparisons of the prevalence
      of asthma symptoms. In phase III the phase I survey was repeated in order to
      assess changes over time. METHODS: The phase I survey was repeated after an
      interval of 5-10 years in 106 centres in 56 countries in children aged 13-14
      years (n = 304,679) and in 66 centres in 37 countries in children aged 6-7 years
      (n = 193,404). RESULTS: The mean symptom prevalence of current wheeze in the last
      12 months changed slightly from 13.2% to 13.7% in the 13-14 year age group (mean
      increase of 0.06% per year) and from 11.1% to 11.6% in the 6-7 year age group
      (mean increase of 0.13% per year). There was also little change in the mean
      symptom prevalence of severe asthma or the symptom prevalence measured with the
      asthma video questionnaire. However, the time trends in asthma symptom prevalence
      showed different regional patterns. In Western Europe, current wheeze decreased
      by 0.07% per year in children aged 13-14 years but increased by 0.20% per year in
      children aged 6-7 years. The corresponding findings per year for the other
      regions in children aged 13-14 years and 6-7 years, respectively, were: Oceania (
      0.39% and -0.21%); Latin America (+0.32% and +0.07%); Northern and Eastern Europe
      (+0.26% and +0.05%); Africa (+0.16% and +0.10%); North America (+0.12% and
      +0.32%); Eastern Mediterranean (-0.10% and +0.79%); Asia-Pacific (+0.07% and 
      0.06%); and the Indian subcontinent (+0.02% and +0.06%). There was a particularly
      marked reduction in current asthma symptom prevalence in English language
      countries (-0.51% and -0.09%). Similar patterns were observed for symptoms of
      severe asthma. However, the percentage of children reported to have had asthma at
      some time in their lives increased by 0.28% per year in the 13-14 year age group
      and by 0.18% per year in the 6-7 year age group. CONCLUSIONS: These findings
      indicate that international differences in asthma symptom prevalence have
      reduced, particularly in the 13-14 year age group, with decreases in prevalence
      in English speaking countries and Western Europe and increases in prevalence in
      regions where prevalence was previously low. Although there was little change in
      the overall prevalence of current wheeze, the percentage of children reported to
      have had asthma increased significantly, possibly reflecting greater awareness of
      this condition and/or changes in diagnostic practice. The increases in asthma
      symptom prevalence in Africa, Latin America and parts of Asia indicate that the
      global burden of asthma is continuing to rise, but the global prevalence
      differences are lessening.

PMID- 17504818
TI  - Clinical investigation of an outbreak of alveolitis and asthma in a car engine
      manufacturing plant.
AB  - BACKGROUND: Exposure to metal working fluid (MWF) has been associated with
      outbreaks of extrinsic allergic alveolitis (EAA) in the USA, with bacterial
      contamination of MWF being a possible cause, but is uncommon in the UK. Twelve
      workers developed EAA in a car engine manufacturing plant in the UK, presenting
      clinically between December 2003 and May 2004. This paper reports the subsequent
      epidemiological investigation of the whole workforce. The study had three aims:
      (1) to measure the extent of the outbreak by identifying other workers who may
      have developed EAA or other work-related respiratory diseases; (2) to provide
      case detection so that those affected could be treated; and (3) to provide
      epidemiological data to identify the cause of the outbreak. METHODS: The outbreak
      was investigated in a three-phase cross-sectional survey of the workforce. In
      phase I a respiratory screening questionnaire was completed by 808/836 workers
      (96.7%) in May 2004. In phase II 481 employees with at least one respiratory
      symptom on screening and 50 asymptomatic controls were invited for investigation
      at the factory in June 2004. This included a questionnaire, spirometry and
      clinical opinion. 454/481 (94.4%) responded and 48/50 (96%) controls. Workers
      were identified who needed further investigation and serial measurements of peak
      expiratory flow (PEF). In phase III 162 employees were seen at the Birmingham
      Occupational Lung Disease clinic. 198 employees returned PEF records, including
      141 of the 162 who attended for clinical investigation. Case definitions for
      diagnoses were agreed. RESULTS: 87 workers (10.4% of the workforce) met case
      definitions for occupational lung disease, comprising EAA (n = 19), occupational
      asthma (n = 74) and humidifier fever (n = 7). 12 workers had more than one
      diagnosis. The peak onset of work-related breathlessness was Spring 2003. The
      proportion of workers affected was higher for those using MWF from a large sump
      (27.3%) than for those working all over the manufacturing area (7.9%) (OR = 4.39,
      p<0.001). Two workers had positive specific provocation tests to the used but not
      the unused MWF solution. CONCLUSIONS: Extensive investigation of the outbreak of
      EAA detected a large number of affected workers, not only with EAA but also
      occupational asthma. This is the largest reported outbreak in Europe. Mist from
      used MWF is the likely cause. In workplaces using MWF there is a need to carry
      out risk assessments, to monitor and maintain fluid quality, to control mist and
      to carry out respiratory health surveillance.

PMID- 17504819
TI  - Prospective study of dietary patterns and chronic obstructive pulmonary disease
      among US men.
AB  - BACKGROUND: Many foods are associated with chronic obstructive pulmonary disease
      (COPD) symptoms or lung function. Because foods are consumed together and
      nutrients may interact, dietary patterns are an alternative way of characterising
      diet. A study was undertaken to assess the relation between dietary patterns and
      newly diagnosed COPD in men. METHODS: Data were collected from a large
      prospective cohort of US men (Health Professionals Follow-up Study). Using
      principal component analysis, two dietary patterns were identified: a prudent
      pattern (high intake of fruits, vegetables, fish and whole grain products) and a
      Western pattern (high intake of refined grains, cured and red meats, desserts and
      French fries). Dietary patterns were categorised into quintiles and Cox
      proportional hazards models were adjusted for age, smoking, pack-years, (pack
      years)(2), race/ethnicity, physician visits, US region, body mass index, physical
      activity, multivitamin use and energy intake. RESULTS: Between 1986 and 1998, 111
      self-reported cases of newly diagnosed COPD were identified among 42,917 men. The
      prudent pattern was inversely associated with the risk of newly diagnosed COPD
      (RR for highest vs lowest quintile 0.50 (95% CI 0.25 to 0.98), p for trend =
      0.02), and the Western pattern was positively associated with the risk of newly
      diagnosed COPD (RR for highest vs lowest quintile 4.56 (95% CI 1.95 to 10.69), p
      for trend <0.001). CONCLUSIONS: In men, a diet rich in fruits, vegetables and
      fish may reduce the risk of COPD whereas a diet rich in refined grains, cured and
      red meats, desserts and French fries may increase the risk of COPD.

PMID- 17504820
TI  - Caspase 7 influences susceptibility to rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to investigate the possible role of the
      caspase 7 (CASP7) in susceptibility to rheumatoid arthritis (RA). METHODS:
      Genotyping of three single nucleotide polymorphisms (SNPs) of the CASP7 gene:
      rs11593766 (G/ T), rs2227310 (C/G) and rs2227309 (G/A) was performed in a total
      of 906 RA patients and 528 matched healthy controls using TaqMan assays. All the
      subjects were of Spanish Caucasian origin. A relative quantification of mRNA
      encoding the non-functional variant of procaspase 7 (isoform beta) vs functional
      isoforms was performed in total RNA from 32 healthy individuals using real-time
      PCR. RESULTS: Only the rs2227309 SNP was found to be associated with
      susceptibility to RA. Frequency of the G allele was significantly higher among RA
      patients [overall frequency of the G allele 74.0% in cases vs 68.4% in controls,
      P = 0.001, Odds ratio (OR) = 1.32, 95% Confidence intervals (95% CI) 1.11-1.56]
      and a higher frequency of GG homozygous individuals was found in the RA patient
      group (overall frequency of GG genotype 56.0% in cases and 46.4% in controls, P =
      0.0005, OR = 1.47, 95%CI 1.18-1.83). A statistically significant deviation was
      observed to compare the relative expression of the procaspase 7 isoform beta in
      samples from individuals stratified according their rs2227309 genotypes (AA + AG:
      1.36 +/- 0.55, n = 19, vs GG: 2.35 +/- 0.74, n = 13; P = 0.0002). CONCLUSION: Our
      results support involvement of the CASP7 gene in the susceptibility to RA. The
      higher production of the no functional variant of CASP7 by individuals with a
      particular genotype could be the basis of this association.

PMID- 17504821
TI  - Effectiveness of adalimumab for rheumatoid arthritis in patients with a history
      of TNF-antagonist therapy in clinical practice.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of adalimumab in patients
      with rheumatoid arthritis (RA) who previously discontinued tumour necrosis factor
      (TNF) antagonists for any reason in clinical practice. METHODS: ReAct (Research
      in Active Rheumatoid Arthritis) was a large, open-label trial that enrolled
      adults with active RA who had previously been treated with traditional disease
      modifying anti-rheumatic drugs or biological response modifiers. Patients self
      administered adalimumab 40 mg subcutaneously every other week for 12 weeks and
      were allowed to enter an optional long-term extension phase. Measures of
      adalimumab effectiveness included American College of Rheumatology (ACR) and
      European League Against Rheumatism (EULAR) response criteria, Disease Activity
      Score 28 (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ
      DI). RESULTS: Of 6610 patients, 899 had a history of etanercept and/or infliximab
      therapy; these patients experienced substantial clinical benefit from adalimumab
      treatment. At week 12, 60% of patients had an ACR20 and 33% had an ACR50
      response; 76% had a moderate and 23% had a good EULAR response. In addition, 12%
      achieved a DAS28 < 2.6, indicating clinical remission, and 13% achieved a HAQ DI
      score <0.5. The allergic adverse event rate, regardless of relationship to
      adalimumab, was 6.5/100-patient-years (PYs) in previously TNF-antagonist-exposed
      patients and 4.3/100-PYs in TNF-antagonist-naive patients. A multiple regression
      analysis indicated no statistically significantly increased risk of serious
      infections in patients who received prior TNF antagonists compared with TNF
      antagonist-naive patients. CONCLUSION: In typical clinical practice, adalimumab
      was effective and well-tolerated in patients with RA previously treated with
      etanercept and/or infliximab.

PMID- 17504822
TI  - Human fetal testis: source of estrogen and target of estrogen action.
AB  - BACKGROUND: Estrogens are involved in masculine fertility and spermatogenesis.
      However, little is known about estrogen involvement in human testicular
      organogenesis. Therefore the aim of this study was to investigate the cellular
      sources and targets of estrogens and their variations in the human testis during
      fetal development. Expression profiles of aromatase (CYP19) and estrogen
      receptors (ER) alpha and beta were analysed in human fetal testes at various
      gestational stages by immunohistochemistry and quantitative RT-PCR. METHODS:
      Fifty-four archival paraffin-embedded and four frozen fetal testes were studied
      by immunohistochemistry and real-time PCR. Tissue quality was confirmed by
      histology and expression of specific functional markers: androgenic enzymes for
      Leydig cells, anti-Mullerian hormone for Sertoli cells and Steel factor receptor
      for germ cells. RESULTS: We demonstrate that the human fetal testes express
      aromatase and ERbeta simultaneously in Sertoli, Leydig and germ cells but are
      devoid of ERalpha. Quantification of positive cells indicates a window of protein
      expression, especially between 13 and 22-24 weeks. Quantitative RT-PCR confirmed
      that the human fetal testis expresses CYP19 and ERbeta but not ERalpha mRNA.
      CONCLUSIONS: Our findings suggest that locally produced estrogens influence human
      testicular development through autocrine and paracrine mechanisms, most notably
      during the period of maximal testicular susceptibility to endocrine disruptors.

PMID- 17504823
TI  - Mutation of SOD1 in ALS: a gain of a loss of function.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by
      motoneuron loss. Some familial cases (fALS) are linked to mutations of superoxide
      dismutase type-1 (SOD1), an antioxidant enzyme whose activity is preserved in
      most mutant forms. Owing to the similarities in sporadic and fALS forms, mutant
      SOD1 animal and cellular models are a useful tool to study the disease. In
      transgenic mice expressing either wild-type (wt) human SOD1 or mutant G93A-SOD1,
      we found that wtSOD1 was present in cytoplasm and in nuclei of motoneurons,
      whereas mutant SOD1 was mainly cytoplasmic. Similar results were obtained in
      immortalized motoneurons (NSC34 cells) expressing either wtSOD1 or G93A-SOD1.
      Analyzing the proteasome activity, responsible for misfolded protein clearance,
      in the two subcellular compartments, we found proteasome impairment only in the
      cytoplasm. The effect of G93A-SOD1 exclusion from nuclei was then analyzed after
      oxidative stress. Cells expressing G93A-SOD1 showed a higher DNA damage compared
      with those expressing wtSOD1, possibly because of a loss of nuclear protection.
      The toxicity of mutant SOD1 might, therefore, arise from an initial misfolding
      (gain of function) reducing nuclear protection from the active enzyme (loss of
      function in the nuclei), a process that may be involved in ALS pathogenesis.

PMID- 17504824
TI  - Neuroimaging in rehabilitation: a resource for clinicians.

PMID- 17504825
TI  - Disabling our diagnostic dilemmas.
AB  - The physical therapy profession's diagnostic dilemma results from its confused
      response to competing issues that affect the physical therapist's role as a
      diagnostician. The major components of the diagnostic dilemma are: (1) the
      competition among new ideas, (2) the complexity of the diagnostic process and
      language used to describe the outcome, (3) the profession's lack of consensus
      regarding the diagnostic classification construct to be embraced, and (4) the
      rapid evolution and impact of new knowledge. The interaction of these 4
      components results in "diagnostic disablement." Whether managing a patient,
      creating a curriculum to educate new physical therapy practitioners, or applying
      for research funding to study the science or practice of diagnostic
      classification, physical therapists face a real challenge in understanding and
      complying with all the current diagnostic requirements of the US health care
      system and the physical therapy profession. This article traces the 4 components
      and considers the strategies the profession can use to resolve its diagnostic
      dilemma. The first step would be to standardize the language that physical
      therapists use to describe or diagnose phenomena within their scope of practice.

PMID- 17504826
TI  - "Harnessing our collective professional power": diagnosis dialog.

PMID- 17504827
TI  - Responsiveness of the movement ability measure: a self-report instrument proposed
      for assessing the effectiveness of physical therapy intervention.
AB  - BACKGROUND AND PURPOSE: Designed as a self-report assessment, the Movement
      Ability Measure (MAM) may contribute to effectiveness research if it proves
      responsive to change. The purpose of this article is to report evidence of
      responsiveness of the MAM. SUBJECTS: Thirty-five adults starting outpatient
      physical therapy intervention completed the MAM at the initial visit, at 2 weeks,
      and at 2 months or discharge. Thirty-four no-intervention volunteers completed
      the MAM twice. METHODS: The MAM responses were analyzed with item response theory
      methods; t tests were used to compare responses across test occasions. RESULTS:
      Paired t tests revealed significant changes in the intervention group at both 2
      weeks and 2 months, with an effect size of 0.90 and a responsiveness index of
      5.62 at discharge. At 2 weeks and at discharge, 57% and 80% of participants,
      respectively, showed gains greater than the minimal clinically important
      difference. Participants in the no-intervention group showed no significant
      change. DISCUSSION AND CONCLUSION: The MAM responses revealed significant and
      clinically important changes following intervention. The MAM shows promise as a
      self-report measure of the effectiveness of physical therapy intervention.

PMID- 17504828
TI  - Validity and reliability of the movement ability measure: a self-report
      instrument proposed for assessing movement across diagnoses and ability levels.
AB  - BACKGROUND AND PURPOSE: Physical therapists lack instruments that assess movement
      across diagnoses and ability levels while focusing on physical therapy-specific
      outcomes. This article describes the creation of a Movement Ability Measure (MAM)
      and initial evidence of validity and reliability. SUBJECTS: More than 300 adult
      volunteers with various movement levels completed the 24-item questionnaire.
      METHODS: Item response theory methods were used to create the MAM and gather
      evidence of content and construct validity, test-retest and other types of
      reliability, and concurrent validity with the California Functional Evaluation
      instrument and self-acknowledgement of movement problems. RESULTS: The intraclass
      correlation coefficient for test-retest reliability was .92. Person separation
      reliability was .98. Correlation (r) with the California Functional Evaluation
      instrument was .76. Respondents who denied having movement problems perceived a
      significantly higher level of movement ability than those who claimed to have a
      little, some, or a lot of movement problems in the preceding week. DISCUSSION AND
      CONCLUSION: The MAM shows promise for documenting perceived movement ability
      across ability levels and diagnoses.

PMID- 17504829
TI  - Use of movement system diagnoses in the management of patients with neuromuscular
      conditions: a multiple-patient case report.
AB  - BACKGROUND AND PURPOSE: Medical diagnoses are not sufficient to guide physical
      therapy intervention. To provide a rational basis for treatment selection by
      physical therapists, we developed a set of diagnoses at the level of impairment
      that are relevant to the human movement system. The diagnoses describe the
      primary human movement system problem and provide a basis for matching a specific
      problem with appropriate treatment. The purposes of this 3-patient case report
      are to illustrate an updated version of the diagnostic system and to show how
      treatment decisions can be made relative to both the movement system diagnosis
      and the patient's prognosis. CASE DESCRIPTION AND OUTCOMES: We diagnosed 3
      patients with hemiplegia due to stroke as having 3 different movement system
      problems: force production deficit, fractionated movement deficit, and perceptual
      deficit. Specific intervention and actual patient outcomes for each case are
      outlined. DISCUSSION: Use of movement system diagnoses may have multiple benefits
      for patient care. The possible benefits include decreasing the variability in
      management of patients with neuromuscular conditions, minimizing the trial-and
      error approach to treatment selection, improving communication among health care
      professionals, and advancing research by enabling creation of homogenous patient
      groupings.

PMID- 17504830
TI  - Proposing 6 dimensions within the construct of movement in the movement continuum
      theory.
AB  - BACKGROUND AND PURPOSE: The Movement Continuum Theory (MCT) provides a potential
      basis for movement assessment and intervention, but "movement" lacks specificity.
      The purposes of this study were to propose and evaluate a subdivision of movement
      into multiple dimensions. SUBJECTS: A convenience sample of 318 adults completed
      a 24-item self-report measure of movement ability. METHODS: A multimethod
      approach was used to identify, operationalize, and test a multidimensional model
      of movement. Data analysis included a comparison of the fit of unidimensional and
      multidimensional models using item response theory methods and inspection of
      response patterns. RESULTS: A model specifying 6 dimensions--flexibility,
      strength, accuracy, speed, adaptability, and endurance--fit respondent data
      significantly better than the unidimensional model, even with high pair-wise
      correlations between dimensions. Response patterns showed large differences
      rather than uniform scores across dimensions for over half of the respondents.
      DISCUSSION AND CONCLUSION: Subdividing movement into the proposed dimensions fits
      the data and potentially strengthens the usefulness of the MCT as a theoretical
      foundation for managing movement effectively.

PMID- 17504831
TI  - Advances in gastrointestinal pharmacotherapy--who would have thought?

PMID- 17504832
TI  - A perspective on 45 years in clinical pharmacy education.

PMID- 17504833
TI  - Pharmacy and generic substitution of antiepileptic drugs: missing in action?
AB  - Generic substitution of antiepileptic drugs is an issue that is gathering a lot
      of attention in the neurology community but is not receiving much attention
      within pharmacy. Several proposals have been drafted that restrict a pharmacist's
      decision-making in generic substitution. These proposals highlight concerns about
      the pharmacy community related to generic substitution. Careful consideration
      needs to be given to these issues by pharmacists and pharmacy professional
      organizations. Unless pharmacy as a profession takes strong positions in support
      of a pharmacist's ability to make decisions about pharmacotherapy and addresses
      many of the pharmacy-related problems of generic substitution, policies that
      negatively impact pharmacy will be established.

PMID- 17504834
TI  - Rates of adverse events of long-acting opioids in a state Medicaid program.
AB  - BACKGROUND: Despite widespread use and emerging safety concerns, data on the
      comparative safety and effectiveness of long-acting opioid (LAO) analgesics are
      weak. OBJECTIVE: To compare rates of adverse events among patients newly
      prescribed an LAO. METHODS: A retrospective observational cohort study using
      Medicaid administrative claims data was conducted examining time until first
      adverse outcome among patients with new prescriptions for methadone, extended
      release (ER) oxycodone, ER morphine, or transdermal fentanyl. Adverse outcomes
      included emergency department (ED) encounters or hospitalizations for opioid
      related adverse events, all-cause ED encounters or hospitalizations, death, and
      diagnoses for opioid-related adverse effects. Cox proportional hazards models
      were used to adjust for a variety of measured covariates overall and within
      subgroups of patients with and without cancer. RESULTS: This study included 5684
      subjects. Patients prescribed ER oxycodone were 55[corrected]% less likely
      (adjusted hazard ratio [HR] 0.45; 95% CI 0.26 to 0.77) to experience an ED or
      hospitalization involving an opioid-related adverse event, 23% lower risk of
      hospitalization (adjusted HR 0.77; 95% CI 0.66 to 0.91), 41% lower risk of
      constipation (adjusted HR 0.59; 95% CI 0.35 to 1.00), and a 29% lower risk of
      death (adjusted HR 0.71; 95% CI 0.54 to 0.94) compared with those prescribed ER
      morphine. Among subjects with noncancer pain, fentanyl was associated with a
      higher risk of ED encounters (adjusted HR 1.27; 95% CI 1.02 to 1.59) and
      methadone was associated with a greater risk of overdose symptoms (adjusted HR
      1.57; 95% CI 1.03 to 2.40) compared with ER morphine. CONCLUSIONS: Our results
      support a modest safety advantage with ER oxycodone compared with ER morphine.
      Among subjects with noncancer pain, fentanyl and methadone were associated with
      an increased risk of an adverse event compared with ER morphine. Additional
      studies are needed to confirm our findings and further clarify risks associated
      with different LAOs.

PMID- 17504835
TI  - Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and
      other opioid adverse effects.
AB  - OBJECTIVE: To review the mechanisms of action of methylnaltrexone and its effects
      on opioid bowel dysfunction, as well as its effects on other opioid-induced
      adverse effects (ADEs), and its potential roles in clinical practice. DATA
      SOURCES: A literature search using the MEDLINE and Cochrane Collaboration
      databases for articles published between 1966 and March 2007 was performed.
      Additional data sources were obtained from manual searches of recent journal
      articles, book chapters, and monographs. An updated literature search showed no
      additional publications. STUDY SELECTION AND DATA EXTRACTION: Abstracts and
      original preclinical and clinical research reports published in the English
      language were identified for review. Review articles, commentaries, and news
      reports of this compound were excluded. Literature related to opioids, opioid
      receptors, opioid antagonists, methylnaltrexone, opioid-induced bowel
      dysfunction, constipation, nausea, and vomiting was evaluated and selected based
      on consideration of the support shown for the proof of concept, mechanistic
      findings, and timeliness. Fifty-eight original articles from preclinical studies
      and clinical trials using methylnaltrexone were identified. Pharmacologic action,
      benefits, and ADEs of methylnaltrexone were reviewed, with a focus on its effects
      on bowel dysfunction after opioids. Emphases were placed on its receptor binding
      activities and therapeutically relevant sites of action (peripheral vs central),
      in which peripheral opioid receptors in the body contribute to physiological and
      drug-induced effects. DATA SYNTHESIS: Morphine and related opioids are associated
      with a number of limiting ADEs, including opioid-induced bowel dysfunction.
      Methylnaltrexone, a quaternary derivative of naltrexone, blocks peripheral
      effects of opioids while sparing central analgesic effects. It is currently under
      late-stage clinical investigation for the treatment of opioid-induced
      constipation in patients with advanced illness. Reported results showed the drug
      to be generally well-tolerated. The rapid reversal of constipation is very
      encouraging. Hastening postoperative discharge may also be possible. CONCLUSIONS:
      Methylnaltrexone has the potential to prevent or treat opioid-induced
      peripherally mediated ADEs on bowel dysfunction without interfering with central
      analgesia. The study of methylnaltrexone leads to a greater understanding of the
      mechanisms of action of opioid pharmacology.

PMID- 17504836
TI  - Providing patient care in community pharmacies: practice and research in Finland.
AB  - OBJECTIVE: To describe the provision of patient care in community pharmacies in
      Finland. FINDINGS: The network of 799 community pharmacies across Finland
      dispensed 42.1 million prescriptions in 2005. Medication counseling has been
      mandated by law since 1983 and only pharmacists are permitted to provide
      therapeutic advice in pharmacies. Measurable improvements in the rates of
      pharmacists' medication counseling have been observed since 2000. Long-term
      national pharmacy practice initiatives commenced with the World Health
      Organization EuroPharm Forum's Questions to Ask About Your Medicines campaign
      from 1993 to 1996. This was followed by the larger Customized Information for the
      Benefit of Community Pharmacy Patients project. Since the late 1990s, Finnish
      pharmacies have actively participated in ongoing national public health programs,
      initially in the areas of asthma and diabetes, and more recently in the treatment
      and prevention of heart disease. Automated dose dispensing and electronic
      prescribing are in the process of wider uptake and implementation. A nationwide
      multidisciplinary project to improve the use of drugs in older people has
      recently been announced and research in this area is underway. DISCUSSION:
      Research has focused on improving the quality of patient care as a strategic
      priority in community pharmacies. The development of community pharmacy services
      in Finland has been characterized by strong collaboration among the professional
      associations, university departments of social pharmacy, continuing education
      centers, and practicing pharmacists. CONCLUSIONS: Implementation of new patient
      care services has required long-term, systematic, and well coordinated actions at
      the local and national levels. Future services will seek to promote the quality
      use of medications and to ensure that rising costs do not limit uniform access to
      drugs by all Finnish residents.

PMID- 17504837
TI  - Complementary and alternative medicine use among Hispanics in the United States.
AB  - OBJECTIVE: To review the use of complementary and alternative medicine (CAM) in
      Hispanics in the US and highlight the modalities most likely to be unfamiliar to
      healthcare practitioners. DATA SOURCES: A search of the literature published in
      English and a subsequent bibliographic search were conducted using MEDLINE,
      International Pharmaceutical Abstracts, EMBASE, Cumulative Index of Nursing and
      Allied Health Literature, and Manual Alternative and Natural Therapy Index System
      (1980-March 2007). Primary search terms included, but were not limited to,
      Hispanic, Latino, complementary and alternative medicine, and dietary
      supplements. Studies that assessed or evaluated the use of CAM in the Hispanic
      population were reviewed. Articles that included both Hispanics and non-Hispanics
      were also included. STUDY SELECTION AND DATA EXTRACTION: The literature search
      yielded 42 articles focused on the use of CAM by Hispanics. Survey was the most
      common method used in these studies, although some hybrid interviews were also
      conducted. DATA SYNTHESIS: Hispanics were identified homogenously in some studies
      and more correctly as a heterogeneous population in others. Some trials examined
      overall CAM use, whereas others looked at specific dietary supplements and herbs.
      Most reports found a higher than expected rate of CAM use in Hispanics (50-90%).
      A number of products potentially unfamiliar to healthcare practitioners, such as
      linden, sapodilla, and star anise, were reported as commonly used in several
      studies. Many studies were limited by the sample size or use of only one Hispanic
      subgroup. CONCLUSIONS: Hispanics use a wide range of CAM therapies, including
      several that may be unfamiliar to healthcare practitioners. Understanding the
      rationale, motivations, and history of Hispanics' use of CAM will enhance the
      cultural competence of healthcare professionals and help address these patients'
      medical needs.

PMID- 17504838
TI  - Prazosin treatment of nightmares related to posttraumatic stress disorder.
AB  - OBJECTIVE: To describe current data evaluating the use of prazosin in adults with
      posttraumatic stress disorder (PTSD) who are experiencing nightmares. DATA
      SOURCES: A literature search using MEDLINE (1966-March 2007) and the Published
      International Literature on Traumatic Stress database (1982-March 2007) was
      conducted using the search terms alpha-antagonist, alpha-blocker, prazosin, and
      posttraumatic stress disorder. References of identified articles were reviewed
      for additional citations. STUDY SELECTION AND DATA EXTRACTION: All English
      language articles regarding the use of prazosin in adults with nightmares related
      to PTSD were reviewed. DATA SYNTHESIS: PTSD is a psychiatric disorder that
      develops in some people after exposure to trauma. Sleep disturbances occur in up
      to 70% of patients with PTSD. Several neurotransmitters have been implicated in
      the pathophysiology of sleep disturbances in PTSD. Adrenergic agents that inhibit
      norepinephrine, such as prazosin, may decrease the arousal produced by
      norepinephrine in response to a stressor. Four open-label studies, 1
      retrospective chart review, and 2 placebo-controlled trials reporting the use of
      prazosin for nightmares related to PTSD were reviewed. All studies included a
      small number of patients (4-59) and evaluated prazosin dosages ranging from 1 to
      20 mg/day. Despite various limitations, all of the studies showed significant
      improvements in the sleep-related symptoms of PTSD following the addition of
      prazosin therapy, based on the Clinician Administered PTSD Scale recurrent
      distressing dreams item and the Clinical Global Impression of Change scale.
      CONCLUSIONS: Prazosin appears to be a promising and fairly well tolerated agent
      for the management of PTSD-related nightmares and sleep disturbances. Further
      well designed trials are warranted to establish its place in therapy.

PMID- 17504839
TI  - Propylthiouracil versus methimazole in treatment of Graves' disease during
      pregnancy.
AB  - OBJECTIVE: To evaluate the evidence supporting the use of propylthiouracil (PTU)
      versus methimazole for the treatment of Graves' disease during pregnancy. DATA
      SOURCES: An English-language literature search was conducted using MEDLINE (1966
      March 2007). Identified articles were then reviewed for additional sources.
      Search terms included hyperthyroidism, Graves' disease, pregnancy,
      propylthiouracil, and methimazole. STUDY SELECTION AND DATA EXTRACTION: All
      clinical trials and case reports that were published in English and reported
      either subjective or objective outcomes were reviewed. DATA SYNTHESIS: Rationale
      supporting the use of PTU over methimazole in treatment of Graves' disease during
      pregnancy is limited. Theories suggesting that PTU has less placental transfer to
      the fetus than methimazole are not supported by current literature. Studies
      demonstrating a causal relationship between methimazole use during pregnancy and
      congenital anomalies and/or fetal hypothyroidism do not exist. CONCLUSIONS: The
      selection of PTU versus methimazole for the treatment of Graves' disease during
      pregnancy should not be based solely on the following assumptions: that PTU
      crosses the placenta less than methimazole, that PTU leads to less fetal
      hypothyroidism, or that exposure to methimazole during pregnancy leads to
      decreased intellectual function in children. However, due to a possible
      association between the use of methimazole during pregnancy and fetal anomalies
      such as aplasia cutis, esophageal atresia, and choanal atresia, methimazole may
      be a less desirable first-line treatment for Graves' disease in pregnancy than
      PTU. Therefore, in the absence of a compelling indication for the use of
      methimazole, PTU should still be considered as the first-line agent in the
      treatment of Graves' disease during pregnancy. Methimazole should be considered a
      viable second choice if the patient is intolerant to PTU, has an allergic
      reaction to PTU, or fails to become euthyroid while receiving PTU.

PMID- 17504840
TI  - Joint-specific hand symptoms and self-reported and performance-based functional
      status in African Americans and Caucasians: The Johnston County Osteoarthritis
      Project.
AB  - OBJECTIVE: To assess associations between joint-specific hand symptoms and self
      reported and performance-based functional status. METHODS: Participants were from
      the population-based Johnston County Osteoarthritis Project. Symptoms in the
      distal interphalangeal (DIP), proximal interphalangeal (PIP), first
      carpometacarpal (CMC), and metacarpophalangeal (MCP) joints were assessed on a 30
      joint diagram of both hands. Self-reported function was assessed by Health
      Assessment Questionnaire (HAQ) and performance-based function by timed repeated
      chair stands and 8-foot walk time. Separate multiple logistic regression models
      examined associations between symptoms in specific hand joint groups, symptoms in
      >/=2 hand joint groups and number of symptomatic hand joints, and functional
      status measures, controlling for age, race/ethnicity, sex, body mass index,
      radiographic knee and hip OA, knee and hip symptoms and depressive symptoms.
      RESULTS: Those with symptomatic hand joint groups were more likely than those
      without these complaints to report more difficulty and require longer times for
      performance measures. Those with 2 or more symptomatic hand joint groups were
      more likely to have higher HAQ scores (OR = 1.97 (1.53 to 2.53)) and require more
      time to complete 5 chair stands (OR = 1.98 (1.23 to 3.18)) and the 8 foot walk
      test (OR = 1.49 (1.12 to 1.99)). CONCLUSIONS: Joint-specific hand symptoms are
      associated with difficulty performing upper- or lower-extremity tasks,
      independent of knee and hip OA and symptoms, suggesting that studies examining
      functional status in OA should not ignore symptomatic joints beyond the joint
      site of interest, even when functional measures appear to be specific for the
      joint site under study.

PMID- 17504841
TI  - EULAR recommendations for the management of systemic lupus erythematosus. Report
      of a Task Force of the EULAR Standing Committee for International Clinical
      Studies Including Therapeutics.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex disease with variable
      presentations, course and prognosis. We sought to develop evidence-based
      recommendations addressing the major issues in the management of SLE. METHODS:
      The EULAR Task Force on SLE comprised 19 specialists and a clinical
      epidemiologist. Key questions for the management of SLE were compiled using the
      Delphi technique. A systematic search of PubMed and Cochrane Library Reports was
      performed using McMaster/Hedges clinical queries' strategies for questions
      related to the diagnosis, prognosis, monitoring and treatment of SLE. For
      neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search
      was conducted using an array of relevant terms. Evidence was categorised based on
      sample size and type of design, and the categories of available evidence were
      identified for each recommendation. The strength of recommendation was assessed
      based on the category of available evidence, and agreement on the statements was
      measured across the 19 specialists. RESULTS: Twelve questions were generated
      regarding the prognosis, diagnosis, monitoring and treatment of SLE, including
      neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus
      nephritis. The evidence to support each proposition was evaluated and scored.
      After discussion and votes, the final recommendations were presented using brief
      statements. The average agreement among experts was 8.8 out of 10. CONCLUSION:
      Recommendations for the management of SLE were developed using an evidence-based
      approach followed by expert consensus with high level of agreement among the
      experts.

PMID- 17504842
TI  - Nucleosomes possess a high affinity for glomerular laminin and collagen IV and
      bind nephritogenic antibodies in murine lupus-like nephritis.
AB  - AIM: Lupus nephritis is closely associated with in vivo autoantibody-binding to
      glomerular membrane-associated electron-dense structures (EDS). The biochemical
      nature and cellular origin of EDS are controversial, and definitive
      characterisation needs to be performed. METHODS: By using the terminal
      transferase biotin-dUTP nick end-labelling (TUNEL) assay at the electron
      microscopic level, we have traced extracellular chromatin within the glomerular
      basement membranes of nephritic (NZBxNZW)F1 mice. The TUNEL assay was
      subsequently used in combination with standard immune electron microscopy (IEM).
      To analyse why chromatin particles associate with membranes, we determined the
      affinity of nucleosomes and DNA for glomerular laminin, collagen IV and the
      mesangial matrix proteoglycan perlecan by surface plasmon resonance. RESULTS:
      This intra-assay colocalisation TUNEL IEM demonstrated that autoantibodies fully
      colocalised with extracellular TUNEL-positive chromatin observed as EDS in
      glomerular membranes, similar to results obtained by the same technique applied
      to human lupus nephritis. Most importantly, these data validate the murine
      variant of lupus nephritis as a model to study origin of extracellular chromatin
      as a key element in human lupus nephritis. Kinetic analyses demonstrated that
      nucleosomes had a high affinity for collagen IV and laminin, but not for
      perlecan. CONCLUSION: Collectively, these results provide firm evidence that
      dominant target structures for nephritogenic autoantibodies are constituted by
      TUNEL-positive chromatin associated with glomerular capillary and mesangial
      matrix membranes at high affinity.

PMID- 17504843
TI  - Concordance of the management of chronic gout in a UK primary-care population
      with the EULAR gout recommendations.
AB  - OBJECTIVES: To assess concordance of the management of chronic gout in UK primary
      care with the European League Against Rheumatism (EULAR) gout recommendations.
      METHODS: A postal questionnaire was sent to all adults aged >30 years registered
      with two general practices. Patients with possible gout attended for clinical
      assessment, at which the diagnosis was verified clinically. Aspects of chronic
      gout management, including provision of lifestyle modification advice, use of
      urate-lowering therapies (ULT) including dose titration to serum urate (SUA)
      level, prophylaxis against acute attacks, and diuretic cessation were assessed in
      accordance with the EULAR recommendations. RESULTS: Of 4249 (32%) completed
      questionnaires returned, 488 reported gout or acute attacks and were invited for
      clinical assessment. Of 359 attendees, 164 clinically confirmed cases of gout
      were identified. Advice regarding alcohol consumption was recalled by 59 (41%),
      weight loss by 36 (25%) and diet by 42 (29%). Allopurinol was the only ULT used
      and was taken by 44 (30%); 31 (70%) were taking 300 mg daily. Mean SUA was lower
      in allopurinol users than non-users (318 vs 434 micromol/l) and was less often
      >360 micromol/l in allopurinol users (23% vs 75%). Eight patients had recently
      commenced allopurinol; two of these also were taking prophylactic colchicine or
      non-steroidal anti-inflammatory drugs. Of 25 patients with diuretic-induced gout,
      16 (64%) were still taking a diuretic. CONCLUSION: Treatment of chronic gout is
      often suboptimal and poorly concordant with EULAR recommendations. Lifestyle
      advice is infrequently offered, and allopurinol is restricted to a minority.
      Persistent hyperuricaemia was often seen in allopurinol non-users, but was also
      in allopurinol users, suggesting that doses >300 mg are often necessary.

PMID- 17504844
TI  - Dialysis catheter insertion with and without peel-away sheaths.

PMID- 17504845
TI  - Neutrophils in acidotic haemodialysed patients have lower intracellular pH and
      inflamed state.
AB  - BACKGROUND: The effect of intracellular pH (pHi) on neutrophils has not been
      clearly defined. METHODS: We used pre-dialysis neutrophils from three groups of
      haemodialysis (HD) patients having different levels of pre-dialysis plasma
      bicarbonate concentrations (PHCO3) and pH values (pre-dialysis PHCO3 of groups A,
      B and C were consistently<or=21, 21-26 and>or=26 mmol/l [mEq/l], respectively)
      and neutrophils from age- and sex-matched healthy controls to determine pHi,
      apoptosis, phagocytosis and oxidative burst reactions in vivo. We also studied,
      in group A, the effect of metabolic acidosis correction on neutrophil function.
      Furthermore, we investigated the effect of intracellular acidification on
      neutrophil functioning in vitro. RESULTS: Neutrophils from the HD patients in
      group A exhibited significantly lower pHi than those in groups B and C. In
      addition, group A neutrophils had significantly delayed apoptosis, enhanced
      phagocytosis and increased oxidative burst reactions compared with those in
      groups B and C. These alterations in neutrophil function in group A were reduced
      by correcting metabolic acidosis over a period of 1 month. Moreover, our in vitro
      studies demonstrated that the pHi of neutrophils is positively correlated with
      apoptosis and inversely correlated with phagocytosis and oxidative burst
      reactions. CONCLUSION: HD patients having low PHCO3 exhibited low neutrophil pHi.
      This intracellular acidification may contribute to the delayed apoptosis,
      enhanced phagocytosis and increased oxidative burst reactions observed in these
      neutrophils compared with neutrophils having normal or higher pHi.

PMID- 17504846
TI  - Steroid-resistant idiopathic childhood nephrosis: overdiagnosed and undertreated.
AB  - BACKGROUND: The rate of complete remission after induction therapy for steroid
      resistant nephrotic syndrome (SRNS) due to either focal segmental
      glomerulosclerosis (FSGS) or minimal change nephrotic syndrome (MCNS) has been
      reported to be <50%. The present retrospective study investigated 86 children
      with SRNS due to FSGS and MCNS and found improved rates of complete remission in
      children with idiopathic FSGS and MCNS after combination therapies using
      ciclosporin A (CSA) and prednisolone (PRED). METHODS: Eighty-six children with
      FSGS or MCNS and with SRNS receiving standard oral PRED therapy were analysed in
      a retrospective, non-randomized study. Fifty-two patients had idiopathic FSGS
      (group 1), 14 patients had MCNS (group 2), and 20 patients had genetic FSGS or
      syndrome-associated FSGS (group 3). In group 1A (n = 25), induction therapy
      consisted of CSA (initial dose 150 mg/day/m(2) divided into two doses) given in
      combination with intravenous methylprednisolone (IV-MPRED 300-1000 mg/day/m(2)
      for 3-8 days) and oral PRED. In group 1B (n = 27), CSA was combined with oral
      PRED (40 mg/m(2) on alternate days). RESULTS: In group 1, patients with
      idiopathic FSGS receiving IV-MPRED + oral PRED + CSA had a significantly better
      outcome than patients treated with oral PRED + CSA (84 vs 64% cumulative
      proportion of sustained complete remission, respectively; P = 0.02, log-rank
      test). Sixteen (40%) out of 40 children entering complete remission had a first
      relapse after a median interval of 1 year. All relapses were successfully treated
      with IV-MPRED + oral PRED + CSA or oral PRED + CSA. Three out of forty responding
      children developed stage 2 chronic kidney disease (CKD), and none advanced to
      stage 3-5; in contrast, 9 out of 12 children with persistent nephrotic syndrome
      (NS) developed CKD stage 2-5 (8 vs 75%, respectively; P < 0.001, Fisher's exact
      test). In group 2, all 14 children with steroid-resistant MCNS went into
      remission after receiving PRED + CSA (n = 11) or IV-MPRED + oral PRED + CSA (n =
      3). No patient developed CKD. In group 3, NS persisted in all 20 children having
      a genetic or syndromic type of FSGS receiving either PRED + CSA (n = 9) or PRED
      alone (n = 11). Seventeen out of 20 patients entered stage 5 CKD and were
      successfully transplanted; one patient developed recurrent NS. CONCLUSION:
      Prolonged and intensified treatment of children with idiopathic non-genetic SRNS
      (FSGS or MCNS) with combined PRED + CSA therapy including IV-MPRED pulses
      resulted in a higher rate of remission when compared with previous reports on
      using CSA mono-therapy or other immunosuppressive combination therapies.

PMID- 17504847
TI  - Burden of illness, visual impairment and health resource utilisation of patients
      with neovascular age-related macular degeneration: results from the UK cohort of
      a five-country cross-sectional study.
AB  - BACKGROUND/AIMS: Quantitative data regarding the impact of neovascular age
      related macular degeneration (NV-AMD) on individuals and society is a
      prerequisite for rational decision-making processes when evaluating alternative
      treatments for the disease. METHODS: 75 bilateral NV-AMD (patients) and 91
      elderly non-AMD (controls) subjects forming the UK cohort of an international
      cross-sectional, observational study were independently analysed. Subjects
      completed a telephone survey including the National Eye Institute Visual Function
      Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the Hospital Anxiety and
      Depression Scale (HADS), history of falls and health resource utilisation.
      RESULTS: Patients with NV-AMD reported substantially worse vision-related
      functioning and overall well-being, including higher depression scores, than
      controls after adjusting for age, gender and co-morbidities (adjusted mean
      scores: NEI-VFQ-25 overall 52.7 vs 90.7, p<0.0001; EQ-5D 0.67 vs 0.77, p =
      0.0273; HADS depression 6.8 vs 4.0, p = 0.0026). Significantly more patients
      reported a need for assistance with daily activities compared with controls
      (25.3% vs 6.6%, p = 0.003). Total annual healthcare utilisation costs were more
      than sevenfold higher for patients with AMD compared with controls ( pound
      3,823.89 vs pound 517.05, respectively; p<0.0001) CONCLUSIONS: Patients with NV
      AMD show a significant decline in quality of life and increased need for daily
      living assistance compared to a control population without AMD. With the
      availability of effective new therapies there is a need for improved early access
      to treatment.

PMID- 17504848
TI  - Objective assessment of intraocular flare after cataract surgery with combined
      primary posterior capsulorhexis and posterior optic buttonholing in adults.
AB  - AIM: Combining primary posterior capsulorhexis (PPC) and posterior optic
      buttonholing (POBH) in cataract surgery is an innovative approach to prevent
      after-cataract formation effectively and to increase postoperative stability of
      the intraocular lens (IOL). The present study was designed to compare the
      postoperative intraocular flare after cataract surgery with combined PPC and POBH
      to conventional in-the-bag implantation of the IOL. METHODS: Fifty consecutive
      age-related cataract patients with cataract surgery under topical anaesthesia in
      both eyes were enrolled prospectively into a prospective, randomised clinical
      trial. In randomised order, cataract surgery with combined PPC and POBH was
      performed in one eye; in the other eye cataract surgery was performed
      conventionally with in-the-bag IOL implantation keeping the posterior lens
      capsule intact. Intraocular flare was measured 1, 2, 4, 6, 12 and 24 h
      postoperatively, as well as 1 week and 1 month postoperatively, using a KOWA FC
      1000 laser flare cell meter. RESULTS: The peak of intraocular flare was observed
      in POBH eyes and eyes with in-the-bag IOL implantation 1 h postoperatively. In
      both groups, the response was steadily decreasing thereafter. During measurements
      at day 1, small though statistically significant higher flare measurements were
      observed in eyes with in-the-bag IOL implantation (p<0.05). At 1 week and 1 month
      postoperatively, intraocular flare measurements were comparable again (p>0.05).
      CONCLUSION: Cataract surgery with combined PPC/POBH showed slightly lower
      postoperative anterior chamber reaction compared to conventional in-the-bag
      implantation during 4-week follow-up, indicating that POBH might trigger somewhat
      less inflammatory response. This could be explained by the posterior capsule
      sandwiching between the optic and the anterior capsule, preventing direct contact
      mediated myofibroblastic trans-differentiation of anterior lens epithelial cells
      with consecutive cytokine depletion.

PMID- 17504849
TI  - Microperimetry and fundus autofluorescence in patients with early age-related
      macular degeneration.
AB  - BACKGROUND: Early age-related macular degeneration (AMD) has been correlated with
      different functional alterations, but the exact relationship between fundus
      lesions and overlying sensitivity is not well known. The aim of this study was to
      compare fundus-related sensitivity (microperimetry) and fundus autofluorescence
      (FAF) of the macular area with drusen and pigment abnormalities in early AMD.
      METHODS: 13 consecutive patients with early AMD and visual acuity of 20/20 were
      studied by means of microperimetry, which automatically analyses macular light
      differential threshold and fixation patterns. Fundus colour photo and FAF of the
      macular area were recorded on the same day. Microperimetry was exactly
      (topographically) superimposed over FAF images. RESULTS: Macular sensitivity
      significantly decreased over large drusen (11.2 +/- 5.6 dB, p<0.0001) and over
      pigment abnormalities (13.1 +/- 3.6 dB, p<0.0001). When both characteristics were
      present the reduction was greater if compared with its absence (9.6 +/- 4.3
      versus 15.0 +/- 4.5 dB, p<0.0001). Sensitivitity reduction was significant in
      areas with altered FAF when compared with areas with normal FAF (p<0.0001).
      CONCLUSIONS: Increased FAF in early AMD has a functional correlate exactly
      quantified by microperimetry. In retinal areas affected by early AMD retinal
      sensitivity deteriorates, despite good visual acuity. Microperimetry may allow
      the early detection of functional impairment caused by these lesions. Both
      microperimetry and FAF may be useful to monitor AMD progression.

PMID- 17504850
TI  - Mutations in the peripherin/RDS gene are an important cause of multifocal pattern
      dystrophy simulating STGD1/fundus flavimaculatus.
AB  - AIM: To describe the phenotype and to analyse the peripherin/RDS gene in 10
      unrelated families with multifocal pattern dystrophy simulating Stargardt disease
      (STGD1). METHODS: The probands of 10 families and 20 affected family members
      underwent an ophthalmic examination including dilated fundus examination, fundus
      autofluorescence imaging and optical coherence tomography (OCT). In all probands
      and in selected family members, fluorescein angiography, electrophysiological
      testing and visual field analysis were performed. Blood samples were obtained
      from affected and unaffected family members for analysis of the peripherin/RDS
      gene. RESULTS: All 10 probands carried mutations in the peripherin/RDS gene. Nine
      different mutations were identified, including six mutations that were not
      described previously. All probands showed a pattern dystrophy with yellow-white
      flecks in the posterior pole that strongly resembled the flecks seen in STGD1, on
      ophthalmoscopy as well as on autofluorescence and OCT. Clinical findings in the
      family members carrying the same mutation as the proband were highly variable,
      ranging from no visible abnormalities to retinitis pigmentosa. CONCLUSIONS:
      Mutations in the peripherin/RDS gene are the major cause of multifocal pattern
      dystrophy simulating STGD1/fundus flavimaculatus. This autosomal dominant
      disorder should be distinguished from autosomal recessive STGD1, in view of the
      different inheritance pattern and the overall better visual prognosis.

PMID- 17504851
TI  - The efficacy of automated "disease/no disease" grading for diabetic retinopathy
      in a systematic screening programme.
AB  - AIM: To assess the efficacy of automated "disease/no disease" grading for
      diabetic retinopathy within a systematic screening programme. METHODS: Anonymised
      images were obtained from consecutive patients attending a regional primary care
      based diabetic retinopathy screening programme. A training set of 1067 images was
      used to develop automated grading algorithms. The final software was tested using
      a separate set of 14 406 images from 6722 patients. The sensitivity and
      specificity of manual and automated systems operating as "disease/no disease"
      graders (detecting poor quality images and any diabetic retinopathy) were
      determined relative to a clinical reference standard. RESULTS: The reference
      standard classified 8.2% of the patients as having ungradeable images (technical
      failures) and 62.5% as having no retinopathy. Detection of technical failures or
      any retinopathy was achieved by manual grading with 86.5% sensitivity (95%
      confidence interval 85.1 to 87.8) and 95.3% specificity (94.6 to 95.9) and by
      automated grading with 90.5% sensitivity (89.3 to 91.6) and 67.4% specificity
      (66.0 to 68.8). Manual and automated grading detected 99.1% and 97.9%,
      respectively, of patients with referable or observable retinopathy/maculopathy.
      Manual and automated grading detected 95.7% and 99.8%, respectively, of technical
      failures. CONCLUSION: Automated "disease/no disease" grading of diabetic
      retinopathy could safely reduce the burden of grading in diabetic retinopathy
      screening programmes.

PMID- 17504852
TI  - Changes in anterior segment morphology in response to illumination and after
      laser iridotomy in Asian eyes: an anterior segment OCT study.
AB  - AIM: Using the anterior segment optical coherence tomography (AS-OCT) to quantify
      changes in anterior segment morphology going from light to dark and following
      laser iridotomy (LI). METHODS: Prospective observational study. 17 consecutive
      subjects without peripheral anterior synechiae undergoing LI were evaluated using
      gonioscopy and AS-OCT. Angle configuration including angle opening distance (AOD)
      at 500 microns anterior to the scleral spur, AOD(500), trabecular-iris space area
      up to 750 microns from the scleral spur, TISA(750) and the increase in angle
      opening going from dark to light conditions was determined. RESULTS: Both mean
      AOD(500) and TISA(750) increased nearly threefold going from dark to light. Both
      also significantly increased following LI (p<0.001) as did gonioscopic grading of
      the angle in all quadrants (p<0.001, McNemar's test). Angles were more than twice
      as wide on average in the dark after LI than before LI (p<0.05). Both the mean
      absolute change and the mean proportionate change in AOD(500) and TISA(750) when
      going from light to dark were greater after LI than before (p<0.05). CONCLUSION:
      Increased illumination as well as LI resulted in significant widening of the
      anterior chamber angle. AS-OCT (which does not require a water bath and can be
      performed with the patient at the slit lamp) identified similar magnitude changes
      as those previously reported using ultrasound biomicroscopy (UBM). Furthermore,
      the angle appears to open more both in absolute terms and and proportionate terms
      in response to illumination after LI.

PMID- 17504854
TI  - The effect of contact lens induced oedema on the accuracy of Goldmann tonometry
      in a mature population.
AB  - AIM: To determine the effect of contact lens induced oedema on the accuracy of
      Goldmann tonometry measurements of intraocular pressure (IOP) in mature subjects.
      METHODS: 22 healthy subjects aged between 50 and 60 years were recruited. Corneal
      curvature, IOP, and central corneal thickness (CCT) were measured before and
      after two hours of monocular closed eye wear of a thick hydroxyethyl methacrylate
      (HEMA) contact lens. Measurements were then repeated at 20 minute intervals for
      one hour after lens removal. RESULTS: Both CCT (+54.1 mum) and IOP (+2.7 mm Hg)
      increased significantly after lens wear (p<0.001, paired t test with Bonferroni
      correction). For the hour following lens removal, the measured IOP was correlated
      to the increase in CCT (r = 0.84, p<0.001), at a rate of 1.0 mm Hg/10 mum (95%
      confidence interval, 0.8 to 1.2 mm Hg/10 mum, linear mixed model analysis).
      CONCLUSIONS: A relatively small increase in CCT from contact lens induced corneal
      oedema caused an overestimation error in Goldmann tonometry measurements of IOP
      in healthy mature subjects.

PMID- 17504853
TI  - Acute retinal necrosis: a national population-based study to assess the
      incidence, methods of diagnosis, treatment strategies and outcomes in the UK.
AB  - AIM: To determine the incidence, methods of diagnosis, treatment strategies and
      outcomes for acute retinal necrosis (ARN) in the UK. METHODS: A 12-month active
      case ascertainment study was carried out between March 2001 and March 2002 to
      record cases of ARN presenting to ophthalmologists via the British
      Ophthalmological Surveillance Unit (BOSU) reporting system. Questionnaires were
      sent to the reporting consultants, requesting data on patient characteristics,
      presentation, clinical findings, investigations and treatment. Diagnosis was made
      using the American Uveitis Society diagnostic criteria. Further questionnaires
      were sent at 2 weeks and 6 months to assess outcome and therapies. RESULTS: 74
      cases of ARN were reported by 58 consultants between March 2001 and March 2002.
      Questionnaires were returned for 49 cases (66.2%), of which 18 (36.7%) were
      excluded. Of the 31 cases included, 22 (71.0%) were male and 9 (29.0%) were
      female. The age range was 13 to 85 years (mean 54.3 years). 28 cases (90.3%) were
      unilateral, with 3 patients (9.7%) presenting with bilateral ARN. An aqueous or
      vitreous biopsy was performed in only 18 patients, with one patient having both.
      Herpes viral DNA analysis was performed on all 19 biopsies, with identification
      of the viral DNA in 16; results from 3 biopsies were not documented. Varicella
      zoster virus (VZV) was the commonest cause identified in 10 patients (56%). Of
      the 31 subjects, 27 (87.1%) were treated for ARN with systemic antiviral
      treatment: with intravenous antiviral in 23 cases (85.2%) and oral antiviral in 4
      cases (14.8%). 21 of these patients went on to receive oral antiviral maintenance
      therapy. In addition to antiviral treatment, systemic steroids were given to 16
      subjects (51.6%). Surgical intervention for retinal detachment was performed on 5
      patients. CONCLUSIONS: During the 12-month study period, 31 cases of ARN met the
      diagnostic criteria set by the American Uveitis Society. The incidence in the UK
      based on this study is approximately 1 case per 1.6 to 2.0 million population per
      year. We have ascertained that the management of ARN throughout the UK is
      variable, suggesting that national guidelines would be of benefit.

PMID- 17504855
TI  - Early detection of glaucoma by means of a novel 3D computer-automated visual
      field test.
AB  - PURPOSE: A recently devised 3D computer-automated threshold Amsler grid test was
      used to identify early and distinctive defects in people with suspected glaucoma.
      Further, the location, shape and depth of these field defects were characterised.
      Finally, the visual fields were compared with those obtained by standard
      automated perimetry. PATIENTS AND METHODS: Glaucoma suspects were defined as
      those having elevated intraocular pressure (>21 mm Hg) or cup-to-disc ratio of
      >0.5. 33 patients and 66 eyes with risk factors for glaucoma were examined. 15
      patients and 23 eyes with no risk factors were tested as controls. The recently
      developed 3D computer-automated threshold Amsler grid test was used. The test
      exhibits a grid on a computer screen at a preselected greyscale and angular
      resolution, and allows patients to trace those areas on the grid that are missing
      in their visual field using a touch screen. The 5-minute test required that the
      patients repeatedly outline scotomas on a touch screen with varied displays of
      contrast while maintaining their gaze on a central fixation marker. A 3D
      depiction of the visual field defects was then obtained that was further
      characterised by the location, shape and depth of the scotomas. The exam was
      repeated three times per eye. The results were compared to Humphrey visual field
      tests (ie, achromatic standard or SITA standard 30-2 or 24-2). RESULTS: In this
      pilot study 79% of the eyes tested in the glaucoma-suspect group repeatedly
      demonstrated visual field loss with the 3D perimetry. The 3D depictions of visual
      field loss associated with these risk factors were all characteristic of or
      compatible with glaucoma. 71% of the eyes demonstrated arcuate defects or a nasal
      step. Constricted visual fields were shown in 29% of the eyes. No visual field
      changes were detected in the control group. CONCLUSIONS: The 3D computer
      automated threshold Amsler grid test may demonstrate visual field abnormalities
      characteristic of glaucoma in glaucoma suspects with normal achromatic Humphrey
      visual field testing. This test may be used as a screening tool for the early
      detection of glaucoma.

PMID- 17504856
TI  - Long-term recovery of the human corneal endothelium after toxic injury by
      benzalkonium chloride.
AB  - INTRODUCTION: The inadvertent intra-ocular administration of benzalkonium
      chloride-preserved hydroxypropyl methylcellulose during cataract surgery at
      another hospital in 1999 resulted in toxic corneal endothelial injury and
      profound postoperative corneal oedema as a result of endothelial decompensation.
      The long-term effect of this adverse event was assessed. METHODS: All 19 patients
      were invited to return for examination including corneal endothelial specular
      microscopy and pachymetry seven years after the incident. Results were compared
      with data from one year after the incident. RESULTS: Five patients attended for
      examination, one had received a penetrating keratoplasty and was, therefore,
      excluded. Ten patients had died and four had moved out of the region and were
      unable to attend. All four study patients were pain free and achieved 6/12 or
      better. Mean central corneal thickness reduced by 13% from 652.6 microm at one
      year to 563.4 microm. Mean central corneal endothelial cell density (n = 3)
      increased 28% from 663.7 cells/mm(2) at one year to 835.7 cells/mm(2) (p<0.05).
      CONCLUSIONS: After toxic injury, corneal endothelial function may have a
      remarkable capacity for recovery even after the first postoperative year. The
      rise in central endothelial cell density may represent cell migration from less
      affected areas or cellular proliferation. Should this unfortunate event recur,
      clinicians may expect continued recovery beyond one year.

PMID- 17504857
TI  - Non-arteritic anterior ischaemic optic neuropathy and presumed sleep apnoea
      syndrome screened by the Sleep Apnea scale of the Sleep Disorders Questionnaire
      (SA-SDQ).
AB  - BACKGROUND: Two recent studies reported over 70% of the patients with non
      arteritic anterior ischaemic optic neuropathy (NAION) had sleep apnoea syndrome
      (SAS) diagnosed by overnight polysomnography. The current study used the Sleep
      Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ) to evaluate this
      association. METHODS: A matched case-control study was conducted among 73 cases
      of NAION matched on age and gender to 73 controls without a history of NAION.
      Information regarding demographics, medical conditions, health behaviours and SAS
      was obtained via a telephone questionnaire that included the SA-SDQ. Conditional
      logistic regression was used to calculate odds ratios (OR) and the 95% confidence
      intervals (CI) for the association between NAION and the SA-SDQ. RESULTS: Cases
      were significantly more likely to report symptoms and characteristics consistent
      with SAS than controls (OR 2.62; 95% CI 1.03 to 6.60) when adjusted for medical
      and health behaviour characteristics. CONCLUSIONS: The results of this study
      suggest that patients with SAS are at increased risk of NAION. Additional
      research in a larger population is needed to confirm the observed results and
      validate the use of the SA-SDQ in patients with NAION.

PMID- 17504858
TI  - Association between integrity of foveal photoreceptor layer and visual acuity in
      branch retinal vein occlusion.
AB  - AIM: To study the correlation between integrity of the photoreceptor layer after
      resolution of macular oedema (MO) associated with branch retinal vein occlusion
      (BRVO) and final visual acuity (VA), and to determine prognostic factors for
      visual outcome. METHODS: We retrospectively studied 46 eyes from 46 patients with
      resolved MO secondary to BRVO, the foveal thickness of which was less than 250
      microm at final observation. We assessed the status of the third high reflectance
      band (HRB) in the fovea using optical coherence tomography (OCT) at final
      observation, and studied OCT images taken at the initial visit in the hope of
      identifying a factor that would be prognostic of visual outcome. RESULTS: No
      differences were found in initial VA or in foveal thickness between eyes with or
      without complete third HRB at final observation. However, final VA in eyes
      without a complete HRB was significantly poorer (p<0.002). Additionally, initial
      status of the third HRB in the parafoveal area of unaffected retina was
      associated with final VA; lack of visualisation of the third HRB at 500 microm (p
      = 0.0104) or 1000 microm (p = 0.0167) from the fovea on initial OCT images was
      associated with poor visual recovery after resolution of the MO. CONCLUSION:
      Integrity of the photoreceptor layer in the fovea is associated with VA in
      resolved MO, and status of the third HRB before treatment might be predictive of
      visual outcome.

PMID- 17504859
TI  - Estimated glomerular filtration rates (eGFR): predicting progression is dependent
      on accuracy.

PMID- 17504860
TI  - How many troponins should we measure to get a clinically significant result?

PMID- 17504861
TI  - Adherence to insulin and its association with glycaemic control in patients with
      type 2 diabetes.
AB  - BACKGROUND: Good glycaemic control improves outcomes in patients with type 2
      diabetes, but the extent to which this depends on adherence to insulin treatment
      is uncertain. AIM: To investigate the association between adherence to insulin
      and glycaemic control in insulin-treated patients with type 2 diabetes. DESIGN:
      Observational records-based study. METHODS: We studied all patients with type 2
      diabetes who were resident in Tayside, Scotland from 1 January 1995 to 30
      September 2001, and who were treated with insulin. Adherence to insulin treatment
      was measured as the annual number of days of insulin coverage on the recommended
      dose, calculated from the amount of drug dispensed at community pharmacies and
      the recommended dose level for each patient. The association between glycaemic
      control (HbA1c), and adherence was determined, as was the influence of
      covariates, including age, sex, duration of diabetes and number of injections per
      day. RESULTS: A total of 1099 people were studied: 574 (52%) males and 525 (48%)
      females, mean +/- SD age 62 +/- 12 years, diabetes duration 10 +/- 7 years.
      Median time in the study (time for which insulin was dispensed) was 1107 (range
      366-2446) days. Insulin prescribed was 58.0 +/- 33.3 IU/day and insulin collected
      from pharmacies was 53.6 +/- 27.1 IU/day. Mean adherence to insulin was thus
      70.6%+/-17.7%. Adherence to insulin (p = 0.0021), BMI (p = 0.0001) and diabetes
      duration (p = 0.0314) were all significant predictors of HbA1c. DISCUSSION:
      Adherence to insulin appears poor in these type 2 diabetes patients, and there
      was a significant relationship between adherence and long-term metabolic control.

PMID- 17504862
TI  - Dual-tracer PET/CT imaging in evaluation of metastatic hepatocellular carcinoma.
AB  - We have reported previously that (11)C-acetate ((11)C-ACT) PET was complementary
      to (18)F-FDG PET in the evaluation of primary hepatocellular carcinoma (HCC) in
      relation to the degree of tumor cellular differentiation. In this retrospective
      study, our goals were to further explore the complementary role of (11)C-ACT and
      (18)F-FDG PET in the detection of metastatic HCC disease, to evaluate the tracer
      characteristics of individual organ metastasis, to identify the risk factors of
      metastasis, and to evaluate how these results could affect patient management.
      METHODS: One hundred twenty-one patients were selected for this study. All
      patients had undergone a "dual-tracer" PET/CT same-day protocol with (11)C-ACT
      PET/CT followed by (18)F-FDG PET/CT. Sets of criteria were chosen to define
      "metastasis" and "no metastasis" on a patient basis. The patients considered as
      true-positive (n = 97) were then divided into 4 groups on the basis of their
      primary HCC tracer avidity: (18)F-FDG-avid group, (11)C-ACT-avid group, (18)F-FDG
      and (11)C-ACT-avid group, and a posttreatment group with metastasis but no
      baseline dual-tracer PET characterization of the primary tumor and no hepatic
      recurrence. RESULTS: On a patient basis, dual-tracer PET/CT had a sensitivity of
      98%, a specificity of 86%, a positive predictive value of 97%, a negative
      predictive value of 90%, and an accuracy of 96% in the detection of HCC
      metastasis. On a lesion basis, 273 metastatic HCC lesions considered as true
      positive were detected and categorized according to the organ or site of
      metastasis: lymph node (abdominal and thoracic, 49%), lung (32%), bone (8%), and
      others (10%). The lesion-based and patient-based detection sensitivities were 60%
      and 64%, respectively, by (11)C-ACT and 77% and 79%, respectively, by (18)F-FDG,
      and they were complementary. In analyzing lesion tracer avidity, there was a
      positive statistical correlation between primary HCC avidity with the general
      tendency of metastasis. Clinically significant changes in management were found
      in patients with true-positive metastasis, of whom 19% were affected by (11)C-ACT
      PET alone. Dual-tracer PET/CT was more effective than single-tracer PET/CT in
      identifying candidates for curative therapy (negative predictive value of dual
      tracer, (18)F-FDG, and (11)C-ACT PET/CT: 90%, 49%, and 37%, respectively).
      CONCLUSION: This study confirmed that (18)F-FDG PET/CT is useful in the
      evaluation of HCC metastasis, although its role in the diagnosis of primary HCC
      is more limited. Dual-tracer PET/CT had an incremental value and complementary
      advantage when compared with single-tracer imaging in the evaluation of HCC
      metastasis.

PMID- 17504863
TI  - Effect of nicotine and ephedrine on the accumulation of 18F-FDG in brown adipose
      tissue.
AB  - This study evaluated the effect of various beta-adrenergic agonists on (18)F-FDG
      uptake in brown adipose tissue (BAT) in rats using ex vivo biodistribution
      studies. METHODS: Caffeine (10 mg/kg of body weight, n = 4), ephedrine (5 mg/kg
      of body weight, n = 4), nicotine (0.8 mg/kg of body weight, n = 9), or a mixture
      of nicotine and ephedrine (0.8 mg/kg of body weight and 5 mg/kg of body weight,
      respectively, n = 9) was injected into the peritoneal cavity of female Lewis rats
      30 min before intravenous (18)F-FDG injection. One hour after injection of (18)F
      FDG, the animals were sacrificed, and BAT, other major organs, and blood were
      extracted. The biodistribution results were compared with body temperature data.
      RESULTS: In the rats injected with nicotine or ephedrine, the mean uptake of
      (18)F-FDG, in percentage injected dose (%ID)/(g of interscapular BAT) x (kg of
      body weight), was significantly increased (7.9-fold for nicotine and 3.7-fold for
      ephedrine), compared to the control rats. Nicotine had the strongest effect on
      (18)F-FDG uptake in BAT. Caffeine increased BAT uptake slightly, but this
      increase did not reach statistical significance. The combination of nicotine and
      ephedrine increased the uptake 12.0-fold, compared with control rats; more than
      either nicotine or ephedrine alone. Uptake of (18)F-FDG in most other major
      organs did not change significantly. The effect of nicotine was blocked by prior
      injection of beta-adrenergic antagonists. A transient decrease in body
      temperature was observed in the nicotine-injected group, and this effect was
      canceled by prior injection of beta-adrenergic antagonists. No significant change
      in baseline temperature was seen before or after beta-adrenergic agonist
      injection. CONCLUSION: Nicotine caused a greater increase in (18)F-FDG uptake in
      BAT than did other interventions, and the effect was increased when nicotine was
      combined with ephedrine. The effect of nicotine was completely blocked by prior
      injection of beta-adrenergic antagonists, indicating that beta-adrenergic
      agonists increase the metabolism of BAT. These preclinical data suggest that
      patients should avoid nicotine and ephedrine before undergoing (18)F-FDG PET to
      minimize (18)F-FDG uptake in BAT.

PMID- 17504864
TI  - Optimized, automated striatal uptake analysis applied to SPECT brain scans of
      Parkinson's disease patients.
AB  - Reliable quantitative dopamine transporter imaging is critical for early and
      accurate diagnosis of Parkinson's disease (PD). Image quantitation is made
      difficult by the variability introduced by manual interventions during the
      quantitative processing steps. A fully automated objective striatal analysis
      (OSA) program was applied to dopamine transporter images acquired from PD
      subjects with early symptoms of suspected parkinsonism and compared with manual
      analysis by a trained image-processing technologist. METHODS: A total of 101
      (123)I-beta-CIT SPECT scans were obtained of subjects recruited to participate in
      the Query-PD Study. Data were reconstructed and then analyzed according to a
      package of scripts (OSA) that reorients the SPECT brain volume to the standard
      geometry of an average scan, automatically locates the striata and occipital
      structures, locates the caudate and putamen, and calculates the background
      subtracted striatal uptake ratio (V3''). The striatal uptake ratio calculated by
      OSA was compared with manual analysis by a trained image-processing technologist.
      Several parameters were varied in the automated analysis, including the number of
      summed transverse slices and the size and separation of the regions of interest
      applied to the caudate and putamen to determine the optimum OSA analysis. The
      parameters giving V3'' with the closest correlation to the manual analysis were
      accepted as optimal. RESULTS: The optimal comparison between the V3'' obtained by
      the human analyst and that obtained by the automated OSA analysis yielded a
      correlation coefficient of 0.96. CONCLUSION: Our optimized OSA delivers V3''
      evaluations that closely correlate with a similar evaluation manually applied by
      a highly trained image-processing technologist.

PMID- 17504865
TI  - Evaluation of image registration in PET/CT of the liver and recommendations for
      optimized imaging.
AB  - Multimodality PET/CT of the liver can be performed with an integrated (hybrid)
      PET/CT scanner or with software fusion of dedicated PET and CT. Accurate anatomic
      correlation and good image quality of both modalities are important
      prerequisites, regardless of the applied method. Registration accuracy is
      influenced by breathing motion differences on PET and CT, which may also have
      impact on (attenuation correction-related) artifacts, especially in the upper
      abdomen. The impact of these issues was evaluated for both hybrid PET/CT and
      software fusion, focused on imaging of the liver. METHODS: Thirty patients
      underwent hybrid PET/CT, 20 with CT during expiration breath-hold (EB) and 10
      with CT during free breathing (FB). Ten additional patients underwent software
      fusion of dedicated PET and dedicated expiration breath-hold CT (SF). The image
      registration accuracy was evaluated at the location of liver borders on CT and
      uncorrected PET images and at the location of liver lesions. Attenuation
      correction artifacts were evaluated by comparison of liver borders on uncorrected
      and attenuation-corrected PET images. CT images were evaluated for the presence
      of breathing artifacts. RESULTS: In EB, 40% of patients had an absolute
      registration error of the diaphragm in the craniocaudal direction of >1 cm
      (range, -16 to 44 mm), and 45% of lesions were mispositioned >1 cm. In 50% of
      cases, attenuation-correction artifacts caused a deformation of the liver dome on
      PET of >1 cm. Poor compliance to breath-hold instructions caused CT artifacts in
      55% of cases. In FB, 30% had registration errors of >1 cm (range, -4 to 16 mm)
      and PET artifacts were less extensive, but all CT images had breathing artifacts.
      As SF allows independent alignment of PET and CT, no registration errors or
      artifacts of >1 cm of the diaphragm occurred. CONCLUSION: Hybrid PET/CT of the
      liver may have significant registration errors and artifacts related to breathing
      motion. The extent of these issues depends on the selected breathing protocol and
      the speed of the CT scanner. No protocol or scanner can guarantee perfect image
      fusion. On the basis of these findings, recommendations were formulated with
      regard to scanner requirements, breathing protocols, and reporting.

PMID- 17504866
TI  - Optimal metabolite curve fitting for kinetic modeling of 11C-WAY-100635.
AB  - Many quantitative imaging protocols that make use of a metabolite-corrected
      arterial input function require the use of a mathematic model to describe the
      rate of metabolism of the radioligand. Commonly, parametric models are fit to
      metabolism data and then the fitted model is used to correct the plasma input
      function. (11)C-WAY 100635 is a rapidly metabolized radioligand used extensively
      in mapping the 5-hydroxytryptamine receptor 1A system. METHODS: To evaluate the
      adequacy of fit of 4 metabolite models, we examined data from 92 subjects who
      received an injection of (11)C-WAY 100635, were imaged with PET, and underwent
      measurement of total plasma concentration and metabolites. The performance of
      these models was assessed according to residual plots, as well as fit and
      information criteria. RESULTS: The study showed that the choice of model has a
      substantial effect on the resulting estimates of outcome measures. CONCLUSION:
      Among the models considered, the Hill model provides the best fit across all
      criteria.

PMID- 17504867
TI  - Biodistribution and radiation dosimetry of the synthetic nonmetabolized amino
      acid analogue anti-18F-FACBC in humans.
AB  - The synthetic leucine amino acid analog anti-1-amino-3-(18)F-fluorocyclobutane-1
      carboxylic acid (anti-(18)F-FACBC) is a recently developed ligand that permits
      the evaluation of the L-amino acid transport system. This study evaluated the
      whole-body radiation burden of anti-(18)F-FACBC in humans. METHODS: Serial whole
      body PET/CT scans of 6 healthy volunteers (3 male and 3 female) were acquired for
      2 h after a bolus injection of anti-(18)F-FACBC (366 +/- 51 MBq). Organ-specific
      time-activity curves were extracted from the reconstructed data and integrated to
      evaluate the individual organ residence times. A uniform activity distribution
      was assumed in the body organs with urine collection after the study. Estimates
      of radiation burden to the human body were calculated on the basis of the
      recommendations of the MIRD committee. The updated dynamic bladder model was used
      to calculate dose to the bladder wall. RESULTS: All volunteers showed initially
      high uptake in the pancreas and liver, followed by rapid clearance. Skeletal
      muscle and bone marrow showed lower and prolonged uptake, with clearance
      dominated by the tracer half-life. The liver was the critical organ, with a mean
      absorbed dose of 52.2 microGy/MBq. The estimated effective dose was 14.1
      microSv/MBq, representing less than 20% of the dose limit recommended by the
      Radioactive Drug Research Committee for a 370-MBq injection. Bladder excretion
      was low and initially observed 6 min after injection, well after peak tracer
      uptake in the body organs. CONCLUSION: The PET whole-body dosimetry estimates
      indicate that an approximately 370-MBq injection of anti-(18)F-FACBC yields good
      imaging and acceptable dosimetry. The nonmetabolized nature of this tracer is
      favorable for extraction of relevant physiologic parameters from kinetic models.

PMID- 17504868
TI  - Diagnostic performance and prognostic value of extravascular retention of 123I
      labeled serum amyloid P component in systemic amyloidosis.
AB  - Serum amyloid P component (SAP) binds to amyloid. (123)I-SAP scintigraphy is used
      to evaluate the extent and distribution of amyloid in systemic amyloidosis and
      has great clinical value in the detection of systemic amyloidosis. The aim of the
      study was to assess during scintigraphy the diagnostic performance and prognostic
      value of a simple parameter describing extravascular (123)I-SAP retention in
      systemic amyloidosis. METHODS: Two hundred megabecquerels of (123)I-labeled human
      SAP was injected intravenously for scintigraphy in 20 controls and in 189
      consecutive patients with systemic and localized amyloidosis. Extravascular
      retention of (123)I-SAP was quantified from serum and urine measurements after 24
      h (EVR(24)) and 48 h. Sensitivity and specificity were assessed, and retention
      was correlated with kidney, heart, liver, and nerve involvement and with
      survival. RESULTS: The cutoff value representing a desired specificity of 90% of
      EVR(24) was 50%. The associated sensitivity of EVR(24) for detecting reactive
      systemic, immunocyte-derived (AL), and hereditary amyloidosis was 65%, 61%, and
      22%, respectively, using a cutoff point of 50%. In AL amyloidosis, the EVR(24)
      increased with the number of organs involved (from a mean of 43% for 1 organ to a
      mean of 81% for 4 organs). The EVR(24) correlated with serum alkaline phosphatase
      (r = 0.63) and with creatinine clearance (r = -0.36). In AL amyloidosis, both
      cardiac involvement (hazard ratio, 3.9; 95% CI, 2.0-7.8) and EVR(24) (hazard
      ratio, 2.0; 95% CI, 1.1-3.9) were independent predictors of survival. CONCLUSION:
      In AL amyloidosis, the EVR(24) is strongly associated with organ involvement and
      with prognosis and might serve as an indicator of the body amyloid load.
      Quantification of SAP retention using the EVR(24) has no additional value over
      (123)I-SAP scintigraphy in the detection of systemic amyloidosis.

PMID- 17504869
TI  - Clinical significance of diffusely increased 18F-FDG uptake in the thyroid gland.
AB  - Our purpose was to determine the clinical significance of diffusely increased
      (18)F-FDG uptake in the thyroid gland as an incidental finding on PET/CT.
      METHODS: All patients who were found to have diffuse thyroid uptake on (18)F-FDG
      PET/CT in our institution between November 2004 and June 2006 were investigated
      and compared with an age- and sex-matched control group. The (18)F-FDG uptake in
      the thyroid was semiquantified using maximum standardized uptake value and
      correlated to the available serum thyroid-stimulating hormone (TSH) and thyroid
      peroxidase (TPO) antibody levels using regression analysis. RESULTS: Of the 4,732
      patients, 138 (2.9%) had diffuse thyroid uptake. Clinical information was
      available for 133 of the 138 patients. Sixty-three (47.4%) had a prior diagnosis
      of hypothyroidism or autoimmune thyroiditis, of whom 56 were receiving thyroxine
      therapy. In the control group, consisting of 133 patients with no thyroid uptake,
      there were 13 (9.8%) with a prior diagnosis of hypothyroidism, 11 of whom were
      receiving thyroxine therapy. In the study group, 38 (28.6%) of 133 patients did
      not undergo any further investigation for thyroid disease, whereas 32 (24.1%) of
      133 patients were examined for thyroid disease after PET. Nineteen were found
      with autoimmune thyroiditis or hypothyroidism, and replacement therapy was
      initiated in 12. No significant correlation was found between maximum
      standardized uptake value and TSH (P = 0.09) or TPO antibody (P = 0.68) levels.
      CONCLUSION: The incidental finding of increased (18)F-FDG uptake in the thyroid
      gland is associated with chronic lymphocytic (Hashimoto's) thyroiditis and does
      not seem to be affected by thyroid hormone therapy. SUV correlated neither with
      the degree of hypothyroidism nor with the titer of TPO antibodies.

PMID- 17504870
TI  - Dynamic and static approaches to quantifying 18F-FDG uptake for measuring cancer
      response to therapy, including the effect of granulocyte CSF.
AB  - The response of cancer to chemotherapy can be quantified using (18)F-FDG to
      indicate changes in tumor metabolism. Quantification using the standardized
      uptake value (SUV) is more feasible for clinical practice than is the metabolic
      rate of (18)F-FDG (MRFDG), which requires longer, dynamic scanning. The
      relationship between MRFDG and SUV depends in part on how each accounts for blood
      clearance of tracer. We tested whether chemotherapy and treatment with
      granulocyte colony-stimulating factor (CSF) changed the blood clearance curves
      and therefore affected the relationship between MRFDG and SUV. METHODS: Thirty
      nine patients with locally advanced breast cancer underwent (18)F-FDG PET before
      and after chemotherapy, including granulocyte CSF. The area under the curve (AUC)
      for blood clearance was determined before and after therapy. MRFDGs were
      determined by graphical analyses, whereas SUVs were calculated using the standard
      formula normalized by body weight. MRFDG and SUVs were compared with each other
      and with tumor response. Paired percentage changes in MRFDG and SUV were also
      divided into tertiles based on pretherapy SUV to investigate differences in the
      relative sensitivity of SUV changes to MRFDG changes due to baseline tumor
      uptake. RESULTS: Despite a small but statistically significant 6% decrease in
      blood AUCs after therapy (P = 0.02), SUV and MRFDG did not differ significantly
      in slope (P = 0.53) or in correlation before and after therapy (r = 0.95 for
      both). Percentage changes in MRFDG and SUV between serial scans correlated with
      each other (r = 0.84) and with patient response (P <or= 0.06). The maximum
      detectable percentage change in SUV and the slope of percentage changes in MRFDG
      versus SUV for the patient tertile with the lowest baseline SUVs (65% +/- 5% [+/
      SE], slope (m) = 0.40 +/- 0.12, n = 13) were significantly lower than for the
      other patients (86% +/- 3%, m = 0.85 +/- 0.10, n = 26, P = 0.01 for both).
      CONCLUSION: Chemotherapy and granulocyte CSF treatment resulted in a lower (18)F
      FDG blood AUC. The maximum detectable percentage change in (18)F-FDG uptake is
      less when quantifying via static SUV than via dynamic MRFDG. This effect is small
      in most patients but may have clinical significance for measuring the response of
      patients with a low pretherapy (18)F-FDG uptake.

PMID- 17504871
TI  - Microglial activation in perinatal rabbit brain induced by intrauterine
      inflammation: detection with 11C-(R)-PK11195 and small-animal PET.
AB  - Intrauterine infection can lead to a fetal inflammatory response syndrome that
      has been implicated as one of the causes of perinatal brain injury leading to
      periventricular leukomalacia (PVL) and cerebral palsy. The presence of activated
      microglial cells has been noted in autopsy specimens of patients with PVL and in
      models of neonatal hypoxia and ischemia. Activated microglial cells can cause
      oligodendrocyte damage and white matter injury by release of inflammatory
      cytokines and production of excitotoxic metabolites. We hypothesized that
      exposure to endotoxin in utero leads to microglial activation in the fetal brain
      that can be monitored in vivo by (11)C-(R)-PK11195 (1-[2-chlorophenyl]-N-methyl-N
      [1-methylpropyl]-3-isoquinoline carboxamide)--a positron-emitting ligand that
      binds peripheral benzodiazepine receptor sites in activated microglia--using
      small-animal PET. METHODS: Pregnant New Zealand White rabbits underwent
      laparotomy and were injected with 20 and 30 microg/kg of Escherichia coli
      lipopolysaccharide along the length of the uterus on day 28 of gestation. The
      pups were born spontaneously at term (31 d) and were scanned using small-animal
      PET after intravenous administration of (11)C-(R)-PK11195 and by MRI on postnatal
      day 1. The standard uptake values (SUVs) of the tracer were calculated for the
      whole brain at 10-min intervals for 60 min after tracer injection. The pups were
      euthanized after the scan, and brains were fixed, sectioned, and stained for
      microglial cells using biotinylated tomato lectin. RESULTS: There was increased
      brain retention of (11)C-(R)-PK11195--as determined by a significant difference
      in the slope of the SUV over time--in the endotoxin-treated pups when compared
      with that of age-matched controls. Immunohistochemical staining showed dose
      dependent changes in activated microglia (increased number and morphologic
      changes) in the periventricular region and hippocampus of the brain of newborn
      rabbit pups exposed to endotoxin in utero. CONCLUSION: Intrauterine inflammation
      leads to activation of microglial cells that may be responsible for the
      development of brain injury and white matter damage in the perinatal period. PET
      with the tracer (11)C-(R)-PK11195 can be used as a noninvasive, sensitive tool
      for determining the presence and progress of neuroinflammation due to perinatal
      insults in newborns.

PMID- 17504872
TI  - Theoretic criteria for antibody penetration into solid tumors and
      micrometastases.
AB  - Targeting tumors with antibody-based therapeutics is a complex task presenting
      multiple kinetic barriers. Antibody internalization and clearance inhibit uptake
      both in solid tumors, limited by tumor vascular permeability, and in
      micrometastases, limited by diffusion. METHODS: A modeling exercise is used to
      introduce 2 simple criteria that must be less than unity for saturation of both
      tumors and micrometastases. The clearance modulus and the Thiele modulus are
      ratios of the plasma clearance rate and antibody catabolism, respectively, to the
      tumor tissue penetration rate. RESULTS: Even low rates of antigen internalization
      from constitutive membrane turnover can significantly retard antibody
      penetration. Rapid clearance of single-chain variable fragments also hinders
      uptake, often more than counterbalancing their more rapid extravasation and
      diffusion. CONCLUSION: The model illustrates that with the large resistance from
      the tumor capillary, antibodies may be more suitable for targeting
      micrometastases than vascularized tumors.

PMID- 17504873
TI  - Aging of acute deep vein thrombosis measured by radiolabeled 99mTc-rt-PA.
AB  - In previous studies, (99m)Tc-recombinant tissue plasminogen activator (rt-PA)
      imaging has had a high sensitivity and specificity for the detection of deep vein
      thrombosis (DVT). In this technique, the plasminogen activation site of rt-PA
      undergoes inactivation but fibrin binding is retained. Uptake of (99m)Tc-rt-PA
      into DVT relies on binding of C-terminal lysine residues on fibrin. It is
      postulated that as the thrombus ages, fewer fibrin sites are available for
      (99m)Tc-rt-PA and that there should be a progressive decrease in (99m)Tc-rt-PA
      uptake in old thrombi as compared with fresh thrombi. The ability to
      differentiate fresh from old thrombus would have significant clinical
      implications in the objective diagnosis of recurrent DVT. Our aim was to examine
      the relative uptake of (99m)Tc-rt-PA in acute DVT over the first 30 d after
      diagnosis. METHODS: Seventy-four patients with acute symptomatic DVT were entered
      into the study. Patients underwent ultrasound and (99m)Tc-rt-PA imaging on days
      1, 7, and 30. RESULTS: Residual thrombus was detected by ultrasonography in 46
      (84%) of 55 patients on day 7 and in 29 (66%) of 44 patients on day 30. Of the
      persisting thrombi on day 7, 72% (33/46) showed (99m)Tc-rt-PA uptake. Of the
      persisting thrombi on day 30, 0% (0/29) showed (99m)Tc-rt-PA uptake. CONCLUSION:
      Uptake of (99m)Tc-rt-PA into DVT was absent 30 d after diagnosis. This finding
      suggests that this imaging technique can distinguish fresh from old thrombus.

PMID- 17504874
TI  - Three-dimensional radiobiologic dosimetry: application of radiobiologic modeling
      to patient-specific 3-dimensional imaging-based internal dosimetry.
AB  - Phantom-based and patient-specific imaging-based dosimetry methodologies have
      traditionally yielded mean organ-absorbed doses or spatial dose distributions
      over tumors and normal organs. In this work, radiobiologic modeling is introduced
      to convert the spatial distribution of absorbed dose into biologically effective
      dose and equivalent uniform dose parameters. The methodology is illustrated using
      data from a thyroid cancer patient treated with radioiodine. METHODS: Three
      registered SPECT/CT scans were used to generate 3-dimensional images of
      radionuclide kinetics (clearance rate) and cumulated activity. The cumulated
      activity image and corresponding CT scan were provided as input into an EGSnrc
      based Monte Carlo calculation: The cumulated activity image was used to define
      the distribution of decays, and an attenuation image derived from CT was used to
      define the corresponding spatial tissue density and composition distribution. The
      rate images were used to convert the spatial absorbed dose distribution to a
      biologically effective dose distribution, which was then used to estimate a
      single equivalent uniform dose for segmented volumes of interest. Equivalent
      uniform dose was also calculated from the absorbed dose distribution directly.
      RESULTS: We validate the method using simple models; compare the dose-volume
      histogram with a previously analyzed clinical case; and give the mean absorbed
      dose, mean biologically effective dose, and equivalent uniform dose for an
      illustrative case of a pediatric thyroid cancer patient with diffuse lung
      metastases. The mean absorbed dose, mean biologically effective dose, and
      equivalent uniform dose for the tumor were 57.7, 58.5, and 25.0 Gy, respectively.
      Corresponding values for normal lung tissue were 9.5, 9.8, and 8.3 Gy,
      respectively. CONCLUSION: The analysis demonstrates the impact of radiobiologic
      modeling on response prediction. The 57% reduction in the equivalent dose value
      for the tumor reflects a high level of dose nonuniformity in the tumor and a
      corresponding reduced likelihood of achieving a tumor response. Such analyses are
      expected to be useful in treatment planning for radionuclide therapy.

PMID- 17504875
TI  - 123I-ITdU-mediated nanoirradiation of DNA efficiently induces cell kill in HL60
      leukemia cells and in doxorubicin-, beta-, or gamma-radiation-resistant cell
      lines.
AB  - Resistance to radiotherapy or chemotherapy is a common cause of treatment failure
      in high-risk leukemias. We evaluated whether selective nanoirradiation of DNA
      with Auger electrons emitted by 5-(123)I-iodo-4'-thio-2'-deoxyuridine ((123)I
      ITdU) can induce cell kill and break resistance to doxorubicin, beta-, and gamma
      irradiation in leukemia cells. METHODS: 4'-thio-2'-deoxyuridine was radiolabeled
      with (123/131)I and purified by high-performance liquid chromatography. Cellular
      uptake, metabolic stability, DNA incorporation of (123)I-ITdU, and the effect of
      the thymidylate synthase (TS) inhibitor 5-fluoro-2'-deoxyuridine (FdUrd) were
      determined in HL60 leukemia cells. DNA damage was assessed with the comet assay
      and quantified by the olive tail moment. Apoptosis induction and irradiation
      induced apoptosis inhibition by benzoylcarbonyl-Val-Ala-Asp-fluoromethyl ketone
      (z-VAD.fmk) were analyzed in leukemia cells using flow cytometry analysis.
      RESULTS: The radiochemical purity of ITdU was 95%. Specific activities were 900
      GBq/micromol for (123)I-ITdU and 200 GBq/micromol for (131)I-ITdU. An in vitro
      cell metabolism study of (123)I-ITdU with wild-type HL60 cells demonstrated an
      uptake of 1.5% of the initial activity/10(6) cells of (123)I-ITdU. Ninety percent
      of absorbed activity from (123)I-ITdU in HL60 cells was specifically incorporated
      into DNA. (123)I-ITdU caused extensive DNA damage (olive tail moment > 12) and
      induced more than 90% apoptosis in wild-type HL60 cells. The broad-spectrum
      inhibitor of caspases zVAD-fmk reduced (123)I-ITdU-induced apoptosis from more
      than 90% to less than 10%, demonstrating that caspases were central for (123)I
      ITdU-induced cell death. Inhibition of TS with FdUrd increased DNA uptake of
      (123)I-ITdU 18-fold and the efficiency of cell kill about 20-fold. In addition,
      (123)I-ITdU induced comparable apoptotic cell death (>90%) in sensitive parental
      leukemia cells and in leukemia cells resistant to beta-irradiation, gamma
      irradiation, or doxorubicin at activities of 1.2, 4.1, 12.4, and 41.3 MBq/mL
      after 72 h. This finding indicates that (123)I-ITdU breaks resistance to beta
      irradiation, gamma-irradiation, and doxorubicin in leukemia cells. CONCLUSION:
      (123)I-ITdU-mediated nanoirradiation of DNA efficiently induced apoptosis in
      sensitive and resistant leukemia cells against doxorubicin, beta-irradiation, and
      gamma-irradiation and may provide a novel treatment strategy for overcoming
      resistance to conventional radiotherapy or chemotherapy in leukemia. Cellular
      uptake and cell kill are highly amplified by inhibiting TS with FdUrd.

PMID- 17504876
TI  - Assessment of severity of coronary artery stenosis in a canine model using the
      PET agent 18F-fluorobenzyl triphenyl phosphonium: comparison with 99mTc
      tetrofosmin.
AB  - Myocardial perfusion imaging plays an important role in clinical management of
      coronary artery disease, but the most commonly used radionuclides significantly
      underestimate the severity of coronary artery stenosis. The objective of this
      study was to evaluate the potential clinical utility of the PET compound (18)F
      fluorobenzyl triphenyl phosphonium ((18)F-FBnTP) and characterize its capacity to
      assess the severity of coronary artery stenosis in a canine model in vivo and ex
      vivo. METHODS: (18)F-FBnTP myocardial uptake was measured in 17 dogs with various
      degrees of stenosis of the left anterior descending (LAD) or circumflex (LCx)
      coronary arteries during adenosine vasodilation, using dynamic PET and gamma-well
      counting. True myocardial blood flow in ischemic (IS) and nonischemic (NIS) beds
      of the left ventricle was determined with radioactive microspheres. (18)F-FBnTP
      and (99m)Tc-tetrofosmin activities were compared in 8 dogs ex vivo. RESULTS: The
      quantitative assessment of the perfusion defect was significantly (P < 0.03) more
      accurate with (18)F-FBnTP than with (99m)Tc-tetrofosmin, in mild (IS/NIS; 0.72 +/
      0.08, 0.93 +/- 0.07, respectively, mean +/- SE) and severe stenosis (0.42 +/-
      0.05, 0.64 +/- 0.08, respectively), compared with microsphere flow (mild, 0.43 +/
      0.06; severe, 0.22 +/- 0.04). The IS/NIS ratio of both radionuclides correlated
      linearly with microsphere flow disparity with a similar slope. Flow defect
      contrast was 2.7 times greater for (18)F-FBnTP than for (99m)Tc-tetrofosmin, as
      inferred from the regression line intercept (0.14 vs. 0.38, respectively). The
      (18)F-FBnTP PET IS/NIS ratio (mild, 0.70 +/- 0.04; severe, 0.46 +/- 0.02), did
      not differ statistically (P >or= 0.330) from that measured ex vivo. A nearly
      identical qualitative and quantitative estimate of stenosis severity was obtained
      by early, short (5-15-min) and delayed, prolonged (30-60-min) (18)F-FBnTP PET
      scans. The stenotic area measured by PET was 16% smaller than that defined by
      tissue staining. CONCLUSION: (18)F-FBnTP PET is a promising new technology for
      rapid noninvasive detection and assessment of perfusion defect severity in the
      myocardium.

PMID- 17504877
TI  - Comparison of 18F-FDG PET and bone scintigraphy in detection of bone metastases
      of thyroid cancer.
AB  - We compared the efficacies of (18)F-FDG PET and (99m)Tc-bone scintigraphy for the
      detection of bone metastases in patients with differentiated thyroid carcinoma
      (DTC). METHODS: We examined 47 patients (32 women, 15 men; mean age +/- SD, 57.0
      +/- 10.7 y) with DTC who had undergone total thyroidectomy and were hospitalized
      to be given (131)I therapy. All patients underwent both whole-body (18)F-FDG PET
      and (99m)Tc-bone scintigraphy. The skeletal system was classified into 11
      anatomic segments and assessed for the presence of bone metastases. Bone
      metastases were verified either when positive findings were obtained on >2
      imaging modalities--(201)Tl scintigraphy, (131)I scintigraphy, and CT--or when
      MRI findings were positive if vertebral MRI was performed. RESULTS: Bone
      metastases were confirmed in 59 of 517 (11%) segments in 18 (38%) of the 47 study
      patients. The sensitivities (visualization rate) for bone metastases on a segment
      basis using (18)F-FDG PET and (99m)Tc-bone scintigraphy were 50 of 59 (84.7%) and
      46 of 59 (78.0%), respectively; the difference between these values was not
      statistically significant. There were only 2 (0.4%) false-positive cases in a
      total of 451 bone segments without bone metastases when examined by (18)F-FDG
      PET, whereas 39 (8.6%) were false-positive when examined by (99m)Tc-bone
      scintigraphy. Therefore, the specificities of (18)F-FDG PET and (99m)Tc-bone
      scintigraphy were 449 of 451 (99.6%) and 412 of 451 (91.4%), respectively; the
      difference between these values was statistically significant (P < 0.001). The
      overall accuracies of (18)F-FDG PET and (99m)Tc-bone scintigraphy were 499 of 510
      (97.8%) and 458 of 510 (89.8%), respectively; the difference between these was
      also statistically significant (P < 0.001). CONCLUSION: The specificity and the
      overall accuracy of (18)F-FDG PET for the diagnosis of bone metastases in
      patients with DTC are higher than those of (99m)Tc-bone scintigraphy, whereas the
      difference in the sensitivities of both modalities is not statistically
      significant. In comparison with (99m)Tc-bone scintigraphy, (18)F-FDG PET is
      superior because of its lower incidence of false-positive results in the
      detection of bone metastases of DTC.

PMID- 17504878
TI  - Identification and evaluation of a new tumor cell-binding peptide, FROP-1.
AB  - Peptides are useful tools for the targeted delivery of radionuclides or
      chemotherapeutic drugs to their site of action within an organism. Given that the
      peptide receptor is overexpressed at the tumor, therapeutically active doses can
      be delivered to the tumor with reduced side effects. Because currently known
      peptides are restricted to a small number of tumors, new molecules and their
      corresponding receptors have to be identified to enlarge the spectrum of
      malignancies that can be diagnosed or treated using tumor-targeting peptides.
      METHODS: A 12-amino-acid peptide phage display system was applied to identify a
      new peptide binding to follicular thyroid carcinoma cells. The properties of the
      radiolabeled peptide were assessed in binding, competition, and internalization
      experiments in a variety of tumor cell lines including FRO82-2 and MCF-7 cells,
      and the pharmacokinetic behavior of the radiolabeled peptide was evaluated in
      tumor-bearing mice. Peptide stability was studied in human serum. RESULTS: After
      5 selection rounds, the new peptide, FROP-1 (EDYELMDLLAYL), was identified. It
      showed binding to follicular thyroid carcinoma as well as anaplastic thyroid
      carcinoma, mammary carcinoma, cervix carcinoma, prostate carcinoma, and cell
      lines derived from head and neck tumors, and low affinity could be observed to
      control cells such as human umbilical vein endothelial cells or immortalized
      keratinocytes. In MCF7 cells, 78% and 86% of the bound activity was internalized
      after 10 and 60 min of incubation, respectively. Stability experiments in human
      serum showed the appearance of a degradation product after 15 min. Tumor uptake
      of the radioactive labeled peptide increased for 45 min in nude mouse models,
      reaching an accumulation level of approximately 3.6 percentage injected dose
      (%ID)/g for FRO82-2 tumors or approximately 3.8 %ID/g for MCF-7 tumors.
      CONCLUSION: The target of FROP-1 is most likely a molecule found generally in
      tumors, making this peptide highly attractive for diagnostic or therapeutic
      applications. However, modifications are needed to increase stability and
      affinity.

PMID- 17504879
TI  - Partial-volume effect in PET tumor imaging.
AB  - PET has the invaluable advantage of being intrinsically quantitative, enabling
      accurate measurements of tracer concentrations in vivo. In PET tumor imaging,
      indices characterizing tumor uptake, such as standardized uptake values, are
      becoming increasingly important, especially in the context of monitoring the
      response to therapy. However, when tracer uptake in small tumors is measured,
      large biases can be introduced by the partial-volume effect (PVE). The purposes
      of this article are to explain what PVE is and to describe its consequences in
      PET tumor imaging. The parameters on which PVE depends are reviewed. Actions that
      can be taken to reduce the errors attributable to PVE are described. Various PVE
      correction schemes are presented, and their applicability to PET tumor imaging is
      discussed.

PMID- 17504880
TI  - Small-animal PET of melanocortin 1 receptor expression using a 18F-labeled alpha
      melanocyte-stimulating hormone analog.
AB  - (18)F-Labeled small synthetic peptides have emerged as attractive probes for
      imaging various molecular targets with PET. The alpha-melanocyte-stimulating
      hormone (alpha-MSH) receptor (melanocortin type 1 receptor [MC1R]) is
      overexpressed in most murine and human melanomas. It is a promising molecular
      target for diagnosis and therapy of melanomas. However, (18)F compounds have not
      been successfully developed for imaging the MC1R. METHODS: In this study, an
      alpha-MSH analog, Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH(2) (NAPamide), was
      radiolabeled with N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB). The
      resulting radiopeptide was evaluated as a potential molecular probe for small
      animal PET of melanoma and MC1R expression in melanoma xenografted mouse models.
      RESULTS: The binding affinity of (19)F-SFB-conjugated NAPamide, (19)F-FB
      NAPamide, was determined to be 7.2 +/- 1.2 nM (mean +/- SD) using B16/F10 cells
      and (125)I-(Tyr(2))-[Nle(4),D-Phe(7)]-alpha-MSH [(125)I-(Tyr(2))-NDP] as a
      radioligand. The biodistribution of (18)F-FB-NAPamide was then investigated in
      C57BL/6 mice bearing subcutaneous murine B16/F10 melanoma tumors with high
      expression of MC1Rs and Fox Chase Scid mice bearing human A375M melanoma with a
      relatively low number of MC1R receptors. Biodistribution experiments showed that
      tumor uptake values (percentage injected dose per gram of tumor [%ID/g]) of (18)F
      FB-NAPamide were 1.19 +/- 0.11 %ID/g and 0.46 +/- 0.11 %ID/g, in B16/F10 and
      A375M xenografted melanoma at 1 h after injection, respectively. Furthermore, the
      B16/F10 tumor uptake was significantly inhibited by coinjection with excess alpha
      MSH peptide (P < 0.05), indicating that (18)F-FB-NAPamide specifically recognizes
      the MC1R in living mice. Small-animal PET of (18)F-FB-NAPamide in mice bearing
      B16/F10 and A375M tumors at 1 h after tail vein injection revealed good B16/F10
      tumor-to-background contrast and low A375M tumor-to-background ratios.
      CONCLUSION: (18)F-FB-NAPamide is a promising molecular probe for alpha-MSH
      receptor-positive melanoma PET and warrants further study.

PMID- 17504881
TI  - Levodopa raises objective pain threshold in Parkinson's disease: a RIII reflex
      study.
AB  - BACKGROUND: Patients suffering from Parkinson's disease (PD) describe painful
      sensations that could be related to neuropathic pain. Experimental data have
      indicated the involvement of basal ganglia and dopaminergic pathways in central
      nociceptive processing. AIM: The objective of this study was to assess and
      compare the effect of levodopa on the objective pain threshold in patients with
      PD and healthy subjects. METHODS: The objective pain threshold was assessed by
      the nociceptive flexion reflex (RIII) in 13 PD patients and 10 healthy subjects.
      Patients and healthy subjects were evaluated under two randomised conditions:
      with levodopa (ON) and without (OFF). RESULTS: Levodopa significantly increased
      the RIII threshold of PD patients (6.9 (1.2) mA in the OFF condition vs 8 (1.1)
      mA in the ON position; p = 0.02). RIII threshold was significantly lower in PD
      patients than in healthy subjects in the OFF condition (6.9 (1.2) mA vs 9.7 (3.4)
      mA; p = 0.02). RIII threshold did not change after levodopa administration in
      healthy subjects. CONCLUSION: These results provide evidence of a dopaminergic
      modulation of objective pain threshold in PD patients. In addition, the decrease
      in RIII threshold in PD patients, in the OFF condition, compared with controls,
      confirms the existence of an objective pain perception disturbance in PD.

PMID- 17504882
TI  - Chronic ataxic neuropathy mimicking dorsal midbrain syndrome.
AB  - We describe the clinical course, with special attention to the disturbance of eye
      movements, of a 29-year-old man with chronic ataxic neuropathy with
      ophthalmoplegia, IgM paraprotein, cold agglutinins and anti-GD1b disialosyl
      antibodies (CANOMAD). Using the magnetic search coil technique, we documented
      convergence during upward saccades and other features suggestive of dorsal
      midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may
      present with clinical findings implicating involvement of the central nervous
      system, which contains ganglioside antigens to anti-GD1b antibodies.

PMID- 17504883
TI  - Torsional deviations with voluntary saccades caused by a unilateral midbrain
      lesion.
AB  - Three dimensional eye rotations were measured using the magnetic search coil
      technique in a patient with a lesion of the right rostral interstitial nucleus of
      the medial longitudinal fasciculus (RIMLF) and in four control subjects. Up to 10
      degree contralesional torsional deviations with each voluntary saccade were
      revealed, which also could be seen during bedside examination. There was no
      spontaneous nystagmus. Based on MRI criteria, the lesion involved the RIMLF but
      spared the interstitial nucleus of Cajal. To date, this deficit has not been
      described in patients. Our results support the hypothesis that the vertical
      torsional saccade generator in humans is organised similarly as in monkeys: each
      RIMLF encodes torsional saccades in one direction, while both participate in
      vertical saccades.

PMID- 17504885
TI  - A typology of behavior problems in preschool children.
AB  - The purpose of this study was to produce a typology of behavior problems in
      preschool children. Distinct subtypes were identified through the use of cluster
      analytic techniques on data from the Behavior Assessment System for Children
      (BASC)-Parent Rating Scales. Analyses were based on archival data collected on a
      sample of 268 children, aged 2 to 5 years, who were referred to determine their
      suitability for a day treatment program. Five distinct and reliable subtypes of
      preschool children's behavior problems emerged. Ratings of adaptive and social
      skills based on the BASC Adaptive Scales and measures from the Parenting Stress
      Index served as external variables to assess the distinctiveness of the derived
      subtypes. The findings provide evidence for the reliability and validity of the
      subtypes identified in this study that are consistent with the findings of
      previous subtyping investigations focusing on school-aged children.

PMID- 17504884
TI  - Risk factors for early visual deterioration in temporal arteritis.
AB  - BACKGROUND: Despite corticosteroid treatment, patients with temporal arteritis
      may continue to lose vision. However, predictors of progressive visual loss are
      not known. METHODS: We retrospectively reviewed 341 consecutive patients with
      suspected temporal arteritis who underwent temporal artery biopsy. 90 patients
      with biopsy proven temporal arteritis were included in our study. RESULTS: Twenty
      one patients (23%) experienced continuous visual symptoms despite steroid therapy
      and 14 among these suffered persistent visual deterioration. Based on univariate
      analysis, visual loss on presentation was associated with disc swelling and a
      history of hypertension. Risk factors for progressive visual loss included older
      age, elevated C reactive protein and disc swelling. CONCLUSION: Although
      corticosteroid therapy improves the visual prognosis in temporal arteritis,
      steroids may not stop the progression of visual loss. Our study reliably
      establishes the risk factors for visual loss in this serious condition. Whether
      addressing these risk factors early in their presentation can alter the visual
      outcome remains unknown. Individual risk anticipating treatment regimens and
      strategies might improve the visual prognosis in temporal arteritis in the
      future.

PMID- 17504886
TI  - Sixteen-item Anxiety Sensitivity Index: confirmatory factor analytic evidence,
      internal consistency, and construct validity in a young adult sample from the
      Netherlands.
AB  - The present investigation examined the factor structure, internal consistency,
      and construct validity of the 16-item Anxiety Sensitivity Index (ASI; Reiss
      Peterson, Gursky, & McNally 1986) in a young adult sample (n = 420) from the
      Netherlands. Confirmatory factor analysis was used to comparatively evaluate two
      factor, three-factor, and four-factor models of the anxiety sensitivity
      construct. Support was found for a hierarchical structure of anxiety sensitivity,
      with one global higher-order factor and four lower-order factors. Internal
      consistency for the global and lower-order factors of the 16-item ASI was
      adequate. Convergent and discriminant associations between the 16-item ASI and
      general mood and panic-specific variables were consistent with anxiety
      sensitivity theory. In addition, incremental validity of the anxiety sensitivity
      construct was established, relative to negative affectivity, for unexpected panic
      attacks and agoraphobic avoidance.

PMID- 17504887
TI  - Convergent validity of the Youth Psychopathic Traits Inventory (YPI): association
      with the Psychopathy Checklist: Youth Version (PCL:YV).
AB  - This study investigates the relationship between the self-report Youth
      Psychopathic Traits Inventory (YPI) and the clinician-rated Psychopathy
      Checklist: Youth Version (PCL:YV). A representative sample of 92 girls and 70
      boys, 12 to 20 years of age (mean age, 17 years), who received services at a
      clinic for adolescents with substance misuse problems, was studied. Moderate
      correlations (r =.30-.51) were found between conceptually corresponding YPI and
      PCL:YV factor scores among both boys and girls, whereas correlations between
      individual subscales of the YPI and items of the PCL:YV were not as consistent. A
      cross-tabulation of groupings based on the three-factor models of the two
      instruments largely supported the categorical convergent validity of the YPI,
      particularly for low and high scorers. Although more studies with larger samples
      are needed, results indicate that the YPI is a cost-effective measure of
      psychopathic traits in adolescents in research settings.

PMID- 17504888
TI  - On the validity and utility of discriminating among impulsivity-like traits.
AB  - The ability to make precise distinctions among related personality constructs
      helps clarify theory and increases the utility of clinical assessment. In three
      studies, the authors evaluated the validity of distinctions among four
      impulsivity-like traits: sensation seeking, lack of planning, lack of
      persistence, and urgency (acting rashly when distressed). Factor analyses
      indicated that lack of planning and lack of persistence are two distinct facets
      of one broader trait, whereas urgency and sensation seeking are both very
      modestly related to each other and to the planning/persistence measures. The
      authors developed interview assessments of each, and multitrait, multimethod
      matrix results indicated clear convergent and discriminant validity among the
      constructs. The distinctions among them were useful: The traits accounted for
      different aspects of risky behaviors. Sensation seeking appeared to relate to the
      frequency of engaging in risky behaviors, and urgency appeared to relate to
      problem levels of involvement in those behaviors.

PMID- 17504889
TI  - Axis I screens and suicide risk in jails: a comparative analysis.
AB  - Mental health professionals conducting screenings in jail settings face
      formidable challenges in identifying inmates at risk for major depression and
      suicide. Psychologists often rely on correctional staff to provide initial
      appraisals of those inmates requiring further evaluation. In a sample of 100 jail
      detainees, the effectiveness of two specialized screens (the Referral Decision
      Scale and Mental Disability/Suicide Intake Screen or MDSIS) and one general
      screen (Personality Assessment Screener or PAS) was evaluated. For suicidal
      ideation, the MDSIS composite score evidenced promise (sensitivity = 1.00;
      specificity = 0.71). In ruling out major depression, the PAS Negative Affect
      subscale was useful for the inmate participants.

PMID- 17504890
TI  - The utility of the PAI and the MMPI-2 for discriminating PTSD, depression, and
      social phobia in trauma-exposed college students.
AB  - This study investigated the Minnesota Multiphasic Personality Inventory-Revised
      (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) and the
      Personality Assessment Inventory (PAI; Morey, 1991) with regard to each
      instrument's utility for discriminating post-traumatic stress disorder (PTSD)
      from depression and social phobia in a sample of college students with mixed
      civilian trauma exposure. Participants were 90 trauma-exposed undergraduates (16
      male, 74 female) classified into one of four groups: PTSD, depressive disorders,
      social phobia, and well-adjusted. For both the PAI and the MMPI-2, profile
      analysis revealed that the groups differed in the elevation and shape of their
      profiles. The PAI Traumatic Stress subscale demonstrated good discriminant
      validity.

PMID- 17504891
TI  - Development and validation of a Response Bias Scale (RBS) for the MMPI-2.
AB  - This study describes the development of a Minnesota Multiphasic Personality
      Inventory (MMPI-2) scale designed to detect negative response bias in forensic
      neuropsychological or disability assessment settings. The Response Bias Scale
      (RBS) consists of 28 MMPI-2 items that discriminated between persons who passed
      or failed the Word Memory Test (WMT), Computerized Assessment of Response Bias
      (CARB), and/or Test of Memory Malingering (TOMM) in a sample of 1,212 nonhead
      injury disability claimants. Incremental validity of the RBS was evaluated by
      comparing its ability to detect poor performance on four separate symptom
      validity tests with that of the F and F(P) scales and the Fake Bad Scale (FBS).
      The RBS consistently outperformed F, F(P), and FBS. Study results suggest that
      the RBS may be a useful addition to existing MMPI-2 validity scales and indices
      in detecting symptom complaints predominantly associated with cognitive response
      bias and overreporting in forensic neuropsychological and disability assessment
      settings.

PMID- 17504892
TI  - C-reactive protein before and after weight loss in overweight women with and
      without polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with reproductive and
      metabolic abnormalities. It is unknown whether overweight women with and without
      PCOS achieve similar benefits from weight loss for cardiovascular risk factors.
      METHOD: Overweight body mass index-matched women with (n = 15) and without (n =
      17) PCOS (weight, 95.3 +/- 17.6 kg; body mass index, 35.6 +/- 5.3 kg/m(2), mean
      +/- sd) followed an 8-wk weight loss regime. RESULTS: All subjects had similar
      reductions in weight (3.9 +/- 3.6 kg, 3.8%, vs. 4.5 +/- 4.1 kg, 4.7%,
      respectively, for PCOS and non-PCOS), waist circumference, fat mass,
      triglycerides, free testosterone, and fasting and postprandial insulin. At
      baseline, C-reactive protein (CRP) between groups was not significantly different
      (5.5 +/- 3.1 mg/liter for PCOS vs. 4.9 +/- 3.0 mg/liter for non-PCOS). There was
      a significant interaction between PCOS status and CRP (P = 0.016) such that CRP
      decreased with weight loss for non-PCOS women (-1.2 +/- 1.8 mg/liter; P = 0.025)
      but not for PCOS women. For all women, the change in CRP correlated with the
      change in weight (r = 0.560; P = 0.003), fat mass (r = 0.477; P = 0.016), and
      postprandial insulin (r = 0.402; P = 0.046). Adiponectin, IL-6, and TNF-alpha
      were not significantly different between groups before or after weight loss. Only
      subjects with baseline CRP levels below the median (4.52 mg/liter) showed
      increases in adiponectin (0.98 +/- 1.3 microg/liter) (P = 0.015) and greater
      reductions in triglycerides (P = 0.001) with weight loss. CONCLUSION: A 4-5%
      weight loss improved lipid, glucose, and insulin profiles in women with and
      without PCOS. This degree of weight loss was not effective in lowering CRP
      concentrations in PCOS women, suggesting that greater weight loss is required in
      this group to achieve equivalent cardiovascular benefit to non-PCOS women.

PMID- 17504893
TI  - Evidence for thyroid hormone as a positive regulator of serum thyrotropin
      bioactivity.
AB  - CONTEXT: The regulation of TSH bioactivity in humans is not completely
      understood. OBJECTIVE: The aim of the study was to investigate the role of serum
      thyroid hormones in regulating the bioactivity of TSH. DESIGN: We determined in
      vitro TSH bioactivity and glycosylation in nine patients (six females and three
      males, age 41.3 yr) with primary hypothyroidism before and after L-T(4)
      replacement, in 11 age- and sex-comparable controls (seven females and four
      males, age 37.6 yr), and in two thyroidectomized patients with TSH-secreting
      adenomas during and after L-T(4) withdrawal. METHODS: In vitro TSH bioactivity
      was measured by a sensitive and specific bioassay based on cAMP generation by
      Chinese hamster ovary cells transfected with human TSH receptor. TSH
      glycosylation was assessed by concanavalin A lectin and ricin column affinity
      chromatography. RESULTS: In vitro TSH bioactivity in hypothyroid patients was low
      as compared with controls (0.48 +/- 0.1 vs. 1.1 +/- 0.2; P = 0.004) and increased
      during L-T(4) (0.48 +/- 0.1 vs. 0.8 +/- 0.1; P = 0.01). A strong significant
      correlation (r = +0.80; P = 0.004, Spearman) was observed between the absolute
      increments of serum TSH bioactivity and T(3) during L-T(4) replacement. The
      degree of sialylation was elevated in hypothyroid patients before treatment (47
      +/- 2.4% vs. 29 +/- 4.3%; P = 0.002) and decreased significantly after L-T(4) (47
      +/- 2.4% vs. 33 +/- 4.3%; P = 0.02). The mannose content of serum TSH in
      hypothyroid patients was similar to controls and did not change during L-T(4). In
      vitro TSH bioactivity also decreased in patients with TSH-secreting adenomas
      during L-T(4) withdrawal. CONCLUSION: These data indicate that serum thyroid
      hormone level is a positive regulator of TSH bioactivity.

PMID- 17504894
TI  - Progressive reduction in body weight after treatment with the amylin analog
      pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose
      escalation study.
AB  - CONTEXT: In previous 1-yr trials, treatment with pramlintide (120 microg), an
      analog of the beta-cell hormone amylin, induced sustained reductions in A1C and
      body weight in insulin-using subjects with type 2 diabetes. OBJECTIVE: To assess
      the potential of pramlintide as an antiobesity agent, we assessed the weight
      effect, safety, and tolerability of pramlintide in non-insulin-treated obese
      subjects with and without type 2 diabetes at doses greater than previously
      studied. DESIGN/SETTING: We performed a randomized, double-blind, placebo
      controlled, multicenter study. PATIENTS: A total of 204 obese subjects [80/20%
      female/male, age 48 +/- 10 yr, and body mass index 37.8 +/- 5.6 kg/m(2) (mean +/-
      SD)] participated in the study. INTERVENTION: For 16 wk, without concomitant
      lifestyle intervention, subjects self-administered pramlintide (nonforced dose
      escalation < or = 240 microg) or placebo via sc injection three times a day
      before meals. MAIN OUTCOME MEASURES: Weight, waist circumference, tolerability,
      and safety were the main outcome measures. RESULTS: Pramlintide was generally
      well tolerated, with 88% of subjects able to escalate to the maximum dose of 240
      microg. Withdrawal rates were similar between placebo (25%) and pramlintide
      treated subjects (29%). Subjects completing 16 wk of pramlintide treatment
      experienced placebo-corrected reductions in body weight of 3.7 +/- 0.5% (3.6 +/-
      0.6 kg; P < 0.001) and waist circumference (3.6 +/- 1.1 cm; P < 0.01).
      Approximately 31% of pramlintide-treated subjects achieved > or =5% weight loss
      (vs. 2% placebo; P < 0.001). More pramlintide than placebo-treated subjects
      reported improvements in appetite control (72% vs. 31%), weight control (63% vs.
      24%), and overall well-being (52% vs. 17%). No unexpected safety signals were
      observed. The most common adverse event reported was mild, transient nausea.
      Pramlintide-treated subjects not reporting nausea experienced weight loss similar
      to those who did (3.6 +/- 0.5% and 3.9 +/- 0.5%, respectively). CONCLUSION: These
      results support continued evaluation of pramlintide as a potential treatment for
      obesity.

PMID- 17504895
TI  - Free/dissociable insulin-like growth factor (IGF)-I, not total IGF-I, correlates
      with growth response during growth hormone treatment in children born small for
      gestational age.
AB  - CONTEXT: IGF-I plays an important role in pre- and postnatal growth. Its serum
      levels are regulated by metabolic and genetic factors. Mean total IGF-I in short,
      small for gestational age (SGA) children is reduced, but within the normal range.
      Free/dissociable IGF-I is the bioactive form of IGF-I. OBJECTIVES: The aim of the
      study was to investigate changes in free IGF-I during GH treatment in short SGA
      children and to evaluate whether free IGF-I levels contribute to predicting first
      year growth response and/or adult height. DESIGN, SETTING, AND INTERVENTION: We
      conducted a randomized, double-blind GH dose-response study with a GH dose of
      either 1 mg/m(2).d (group A) or 2 mg/m(2).d (group B). Free IGF-I, total IGF-I,
      and IGF binding protein (IGFBP)-3 were determined at baseline, after 1 and 5 yr,
      at stop, and 6 months after GH discontinuation. PATIENTS: We studied 73 (46 male)
      short SGA children (36 group A) with a baseline mean age of 7.7 (2.2) yr and a
      mean GH duration of 8.2 (2.1) yr. MAIN OUTCOME MEASURES: Untreated SGA children
      had a mean free IGF-I sd score (SDS) of -0.2 (1.2), not related to total IGF-I.
      During GH therapy, free IGF-I significantly increased to 1.6 (0.7) SDS, as did
      total IGF-I and IGFBP-3 [2.0 (0.8) and 1.3 (0.9), respectively]. Multiple
      regression analysis showed that baseline free IGF-I and IGFBP-3 were negatively
      correlated with adult height SDS, whereas baseline bone age delay, target height
      SDS, baseline height SDS, and GH dose were positively correlated. Free IGF-I was
      also negatively correlated with first-year growth response. CONCLUSIONS:
      Circulating baseline free IGF-I and IGFBP-3 were better predictors for adult
      height in GH-treated SGA children than total IGF-I, or total IGF-I to IGFBP-3
      ratio. This suggests a possible role for free IGF-I measurement in predicting the
      effect of GH therapy in short SGA children.

PMID- 17504896
TI  - An increased incidence of overt hypothyroidism after iodine fortification of salt
      in Denmark: a prospective population study.
AB  - CONTEXT: Iodine fortification (IF) of salt was introduced in Denmark in 1998.
      Little is known about the effect of a minor increase in iodine intake on the
      incidence of hypothyroidism. We prospectively identified all new cases of overt
      hypothyroidism in two areas of Denmark before and for the first 7 yr after IF had
      been introduced. METHODS: A computer-based register was used to identify
      continuously all new cases of overt hypothyroidism in two subcohorts with
      previous moderate and mild iodine deficiency (ID), respectively (Aalborg, n =
      310,124, urinary iodine = 45 microg/liter; and Copenhagen, n = 225,707, urinary
      iodine = 61 microg/liter). Data were obtained 1) before IF (1997-1998), 2) during
      voluntary IF (1999-2000), 3) during early (2001-2002) and 4) during late (2003
      2005) period with mandatory IF. RESULTS: The overall incidence rate of
      hypothyroidism increased during the study period: baseline, 38.3/100,000.yr;
      voluntary IF, 43.7 (not significant vs. baseline); early mandatory IF, 48.7 [vs.
      baseline, rate ratio (RR) = 1.27; 95% confidence interval (CI) = 1.10-1.47]; and
      late mandatory IF, 47.2 (vs. baseline, RR = 1.23; 95% CI = 1.07-1.42). There was
      a geographic difference because hypothyroidism increased only in the area with
      previous moderate ID: Aalborg, late mandatory IF vs. baseline, 40.3/29.7 (RR =
      1.11; 95% CI = 1.11-1.66); Copenhagen, 56.7/51.6 (RR = 1.10; 95% CI = 0.90-1.34).
      The increase occurred in young and middle-aged adults. CONCLUSION: Even a
      cautious iodization of salt was accompanied by a moderate increase in the
      incidence rate of overt hypothyroidism. This occurred primarily in young and
      middle-aged subjects with previous moderate ID.

PMID- 17504897
TI  - Random variability in congenital hypothyroidism from thyroid dysgenesis over 16
      years in Quebec.
AB  - CONTEXT: Research on the etiology of congenital hypothyroidism from thyroid
      dysgenesis (CHTD) (comprising mostly ectopy and agenesis) over the past decade
      has focused on genetic mechanisms. However, the possibility that environmental
      factors might be involved has been raised by studies showing a seasonal
      variability of the incidence of CHTD. OBJECTIVES: The objective of this study was
      to assess the variability in incidence of CHTD in the province of Quebec, Canada.
      DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURE: The Quebec provincial
      newborn screening database was analyzed from January 1990 to December 2005. Only
      cases of permanent congenital hypothyroidism with thyroid ectopy or agenesis on
      scintigraphy were analyzed. RESULTS: During the study period, 1,303,341 children
      were screened, and 424 cases of permanent congenital hypothyroidism were
      diagnosed, giving an overall incidence of 1:3074. Of these, 306 had CHTD (overall
      incidence 1:4259) from either ectopy (n = 231) or agenesis (n = 75). Over the 16
      yr of the study, this incidence remained stable (P = 0.57), and no significant
      variability in monthly incidence was found (P = 0.87). CONCLUSIONS: The incidence
      of CHTD did not vary over the observation period, and its monthly variation was
      random. Therefore, environmental factors do not appear to play a significant role
      in the etiology of CHTD.

PMID- 17504898
TI  - The type II iodothyronine deiodinase is up-regulated in skeletal muscle during
      prolonged critical illness.
AB  - CONTEXT: Critical illness is associated with the low T(3) syndrome. It remains
      unclear whether altered type II deiodinase activity (D2) in skeletal muscle
      contributes to this syndrome. OBJECTIVE: Our objective was to study D2 expression
      and activity in skeletal muscle of acute and prolonged critically ill patients.
      DESIGN AND SETTING: We conducted a clinical observational study in acute and
      prolonged critical illness with comparison with healthy controls at a university
      hospital surgical intensive care unit. PATIENTS: Subjects included 63 prolonged
      critically ill patients who died in the intensive care unit, 21 acutely ill
      patients, and 38 controls matched for age, gender, and body mass index. RESULTS:
      Elevated expression of the D2 gene and D2 activity in skeletal muscle of
      prolonged, but not acute, critically ill patients were observed in the face of
      low circulating thyroid hormone levels. CONCLUSIONS: Reduced D2 activity does not
      appear to play a role in the pathogenesis of the low T(3) syndrome of critical
      illness.

PMID- 17504899
TI  - Isolated 46,XY gonadal dysgenesis in two sisters caused by a Xp21.2 interstitial
      duplication containing the DAX1 gene.
AB  - CONTEXT: Testis development is a tightly regulated process that requires an
      efficient and coordinated spatiotemporal action of many factors, and it has been
      shown that several genes involved in gonadal development exert a dosage effect.
      Chromosomal imbalances have been reported in several patients presenting with
      gonadal dysgenesis as part of severe dysmorphic phenotypes. RESULTS: We screened
      for submicroscopic DNA copy number variations in two sisters with an apparent
      normal 46,XY karyotype and female external genitalia due to gonadal dysgenesis,
      and in which mutations in known candidate genes had been excluded. By high
      resolution tiling bacterial artificial chromosome array comparative genome
      hybridization, a submicroscopic duplication at Xp21.2 containing DAX1 (NR0B1) was
      identified. Using fluorescence in situ hybridization, multiple ligation probe
      amplification, and PCR, the rearrangement was further characterized. This
      revealed a 637-kb tandem duplication that in addition to DAX1 includes the four
      MAGEB genes, the hypothetical gene CXorf21, GK, and part of the MAP3K7IP3 gene.
      Sequencing and analysis of the breakpoint boundaries and duplication junction
      suggest that the duplication originated through a coupled homologous and
      nonhomologous recombination process. CONCLUSIONS: This represents the first
      duplication on Xp21.2 identified in patients with isolated gonadal dysgenesis
      because all previously described XY subjects with Xp21 duplications presented
      with gonadal dysgenesis as part of a more complex phenotype, including mental
      retardation and/or malformations. Thus, our data support DAX1 as a dosage
      sensitive gene responsible for gonadal dysgenesis and highlight the importance of
      considering DAX1 locus duplications in the evaluation of all cases of 46,XY
      gonadal dysgenesis.

PMID- 17504900
TI  - 11p15 imprinting center region 1 loss of methylation is a common and specific
      cause of typical Russell-Silver syndrome: clinical scoring system and epigenetic
      phenotypic correlations.
AB  - CONTEXT: Russell-Silver syndrome (RSS), characterized by intrauterine and
      postnatal growth retardation, dysmorphic features, and frequent body asymmetry,
      spares cranial growth. Maternal uniparental disomy for chromosome 7 (mUPD7) is
      found in 5-10% of cases. We identified loss of methylation (LOM) of 11p15
      Imprinting Center Region 1 (ICR1) domain (including IGF-II) as a mechanism
      leading to RSS. OBJECTIVE: The aim was to screen for 11p15 epimutation and mUPD7
      in RSS and non-RSS small-for-gestational-age (SGA) patients and identify
      epigenetic-phenotypic correlations. STUDIED POPULATION AND METHODS: A total of
      127 SGA patients were analyzed. Clinical diagnosis of RSS was established when
      the criterion of being SGA was associated with at least three of five criteria:
      postnatal growth retardation, relative macrocephaly, prominent forehead, body
      asymmetry, and feeding difficulties. Serum IGF-II was evaluated for 82 patients.
      RESULTS: Of the 127 SGA patients, 58 were diagnosed with RSS; 37 of these (63.8%)
      displayed partial LOM of the 11p15 ICR1 domain, and three (5.2%) had mUPD7. No
      molecular abnormalities were found in the non-RSS SGA group (n = 69). Birth
      weight, birth length, and postnatal body mass index (BMI) were lower in the
      abnormal 11p15 RSS group (ab-ICR1-RSS) than in the normal 11p15 RSS group [-3.4
      vs.-2.6 SD score (SDS), -4.4 vs.-3.4 SDS, and -2.5 vs.-1.6 SDS, respectively; P <
      0.05]. Among RSS patients, prominent forehead, relative macrocephaly, body
      asymmetry, and low BMI were significantly associated with ICR1 LOM. All ab-ICR1
      RSS patients had at least four of five criteria of the scoring system. Postnatal
      IGF-II levels were within normal values. CONCLUSION: The 11p15 ICR1 epimutation
      is a major, specific cause of RSS exhibiting failure to thrive. We propose a
      clinical scoring system (including a BMI < -2 SDS), highly predictive of 11p15
      ICR1 LOM, for the diagnosis of RSS.

PMID- 17504901
TI  - Impact of fatness, fitness, and ethnicity on the relationship of nocturnal
      ghrelin to 24-hour luteinizing hormone concentrations in adolescent girls.
AB  - CONTEXT: Ghrelin is related to energy balance that regulates food intake.
      OBJECTIVE: The aim was to explore whether ghrelin would be linked to differences
      in fitness in adolescent girls, whose menstrual cycles are sensitive to changes
      in energy balance. METHODS: A total of 72 girls, ages 14-21 yr, including five
      with amenorrhea, were studied in the follicular phase. LH was sampled every 10
      min over 24-h, and ghrelin was measured hourly between 2300 and 0300 h. Body
      composition was measured by dual x-ray absorptiometry. Fitness was characterized
      by reported frequency of exercise per week and by maximal oxygen consumption with
      "high" vs. "low" fitness groups defined from maximal oxygen consumption norms for
      this population. Data were analyzed with SAS software (SAS Institute Inc., Cary,
      NC). RESULTS: Ghrelin was related to percent body fat (P = 0.038; R(2) 0.07),
      weekly exercise (P = 0.032; R(2) 0.07), and 24-h mean LH (P = 0.002; R(2) 0.13).
      The ghrelin relationship with LH was more pronounced in the low-fitness group. In
      multiple regression models, 24-h LH was an independent predictor of ghrelin after
      adjusting for percent body fat, fitness, exercise, or age. Ghrelin was higher in
      Caucasian girls than in African-American girls after adjusting for covariates at
      0200 h (P = 0.017). CONCLUSIONS: Twenty-four-hour LH is an independent predictor
      of nighttime ghrelin concentrations in postpubertal adolescent girls. Diverging
      patterns in ghrelin may reflect differences in exercise patterns and/or may be
      influenced by ethnicity. These data introduce ghrelin as a biomarker of
      individual differences in energy balance during the menstrual cycle and across
      ethnicities.

PMID- 17504902
TI  - Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase
      activation, and proliferation of endometriotic stromal cells.
AB  - CONTEXT: Metformin, a widely used treatment for diabetes that improves insulin
      sensitivity, also has both antiinflammatory properties and a modulatory effect on
      ovarian steroid production, two actions that have been suggested to be
      efficacious in therapy for endometriosis. OBJECTIVE: To determine whether
      metformin may be effective for the treatment of endometriosis, we evaluated the
      effects of this agent on inflammatory response, estradiol production, and
      proliferation of endometriotic stromal cells (ESCs). DESIGN: ESCs derived from
      ovarian endometriomas were cultured with various concentrations of metformin.
      MAIN OUTCOME MEASURES: IL-8 production, mRNA expression and aromatase activity,
      and 5-bromo-2'-deoxyuridine incorporation in ESCs were measured. RESULTS:
      Metformin dose-dependently suppressed IL-1beta-induced IL-8 production, cAMP
      induced mRNA expression and aromatase activity, and 5-bromo-2'-deoxyuridine
      incorporation in ESCs. CONCLUSION: These results suggest that further
      investigation into the unique therapeutic potential of metformin as an
      antiendometriotic drug is warranted.

PMID- 17504903
TI  - transient scrotal hyperthermia and levonorgestrel enhance testosterone-induced
      spermatogenesis suppression in men through increased germ cell apoptosis.
AB  - CONTEXT: In rodents and monkeys, a combination of hormonal and physical agents
      accelerates germ cell death. OBJECTIVE: A "proof of concept" study was performed
      to investigate whether addition of heat exposure or a progestin to an androgen
      induces germ cell death and more complete and rapid spermatogenesis suppression.
      DESIGN AND SETTINGS: A randomized clinical trial was performed at academic
      medical centers. PARTICIPANTS: We treated four groups of healthy male volunteers
      (18 per group) for 18 wk: 1) testosterone undecanoate (TU) 1000 mg im (first
      dose), followed by 500 mg im every 6 wk; 2) submersion of scrota at 43 C in water
      for 30 min/d for 6 consecutive days; 3) TU plus heat; and 4) TU plus oral
      levonorgestrel (LNG) 250 microg/d. MAIN OUTCOME MEASURES: Semen parameters,
      testicular histology, and germ cell apoptosis were the main outcome measures.
      RESULTS: Heat alone and TU plus heat suppressed sperm counts more than TU alone
      by wk 6. By wk 9, recovery began in the heat only group, whereas spermatogenesis
      remained suppressed in the TU plus heat group. Oral LNG plus TU suppressed
      spermatogenesis earlier and more severely than TU alone. At wk 2, significantly
      greater germ cell apoptosis occurred in heat and heat plus TU subjects, but not
      in subjects without heat treatment, compared with pretreatment subjects. By 9 wk,
      markedly smaller seminiferous tubule diameters and fewer spermatocytes and
      spermatids were noted in all 12 biopsies from men receiving TU, TU plus LNG, with
      most dramatic differences for the TU plus heat group, whereas no differences from
      pretreatment biopsies were observed in men who received heat treatment only.
      CONCLUSIONS: Heat causes a rapid and transient suppression of spermatogenesis. TU
      plus heat resulted in low-sperm output that was maintained by continuous
      treatment with TU. Addition of an oral progestin accelerated spermatogenesis
      suppression by TU alone. Increased germ cell apoptosis contributed to suppression
      of spermatogenesis.

PMID- 17504904
TI  - Insulin resistance, insulin response, and obesity as indicators of metabolic
      risk.
AB  - CONTEXT: Insulin resistance (IR) and obesity, especially abdominal obesity, are
      regarded as central pathophysiological features of a cluster of cardiovascular
      risk factors (CVRFs), but their relative roles remain undefined. Moreover, the
      differential impact of IR viz. insulin response has not been evaluated.
      OBJECTIVE: The objective of this study was to dissect out the impact of obesity,
      abdominal obesity, and IR/insulin response on CVRF. DESIGN: This was a cross
      sectional study. SETTING: The study was conducted at 21 research centers in
      Europe. SUBJECTS: The study included a cohort of 1308 nondiabetic subjects [718
      women and 590 men, age 30-60 yr, body mass index (BMI) 17-44 kg.m(-2)]. MAIN
      OUTCOME MEASURES: We measured IR (by a standardized euglycemic insulin clamp),
      waist girth, insulin response to an oral glucose tolerance test, and major CVRF,
      and analyzed their associations by multivariate models and factor analysis.
      RESULTS: BMI was positively related to all CVRFs. Waist circumference was related
      to higher blood pressure and serum triglycerides and lower high-density
      lipoprotein-cholesterol, IR to reduced glucose tolerance, higher free fatty
      acids, triglyceride and low-density lipoprotein-cholesterol, and lower high
      density lipoprotein-cholesterol, and insulin response to higher heart rate, blood
      pressure and fasting glucose, and the same dyslipidemic profile as IR (P < or =
      0.05 for all). By factor analysis, three main factors (related to IR, age, and
      fatness, respectively) appeared to underlie this pattern of associations. Each of
      BMI, waist girth, IR, and insulin response was independently associated with
      total CVRF load (all P < 0.001). CONCLUSIONS: When IR, fat mass and distribution,
      and insulin response are measured simultaneously in a large cohort, no one factor
      stands out as the sole driving force of the CVRF cluster, each being associated
      with one or more physiological pathways according to known cause-effect
      relationships.

PMID- 17504905
TI  - Cytotoxic T-lymphocyte associated antigen 4 gene polymorphisms and autoimmune
      thyroid disease: a meta-analysis.
AB  - CONTEXT: Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) polymorphisms have
      been widely examined for their associations with autoimmune thyroid diseases
      [Graves' disease (GD) and Hashimoto thyroiditis (HT)], but their relative
      population effect remains unclear. OBJECTIVE: The aim was to generate large-scale
      evidence on whether the CTLA-4 polymorphisms (A49G and CT60) and haplotypes
      thereof increase the susceptibility to GD and/or HT. DESIGN, SETTING, AND
      PARTICIPANTS: Meta-analyses of group-level data were reviewed from 32 (11,019
      subjects) and 12 (4,479) published and unpublished studies for the association of
      the A49G polymorphism with GD and HT, respectively (PubMed and HuGeNet search
      until July 2006). There were 15 (n = 7246) and six (n = 3086) studies available
      for the CT60 polymorphism, respectively. Meta-analyses of individual-level data
      from 10 (4906 subjects) and five (2386) collaborating teams for GD and HT,
      respectively, were also reviewed. MAIN OUTCOME MEASURES: Association of gene
      variants and haplotypes with GD and HT was measured. RESULTS: Group-level data
      suggested significant associations with GD and HT for both A49G [odds ratios 1.49
      (P = 6 x 10(-14)) and 1.29 (P = 0.001) per G allele, respectively] and CT60 [1.45
      (P = 2 x 10(-9)) and 1.64 (P = 0.003) per G allele, respectively]. Results were
      consistent between Asian and Caucasian descent subjects. Individual-level data
      showed that compared with the AA haplotype, the risk conferred by the GG
      haplotype was 1.49 (95% confidence interval 1.31,1.70) and 1.36 (95% confidence
      interval 1.16,1.59) for GD and HT, respectively. Data were consistent with a dose
      response effect for the G allele of CT60. CONCLUSION: The CT60 polymorphism of
      CTLA-4 maps an important genetic determinant for the risk of both GD and HT
      across diverse populations.

PMID- 17504906
TI  - The catechol-O-methyltransferase Met158 low-activity allele and association with
      nonvertebral fracture risk in elderly men.
AB  - CONTEXT: Because sex steroids play an important role in bone development,
      variants in genes encoding proteins involved in estrogen synthesis and metabolism
      could contribute to interindividual variation in bone parameters and fracture
      risk. An example is catechol-O-methyltransferase (COMT), an estrogen-degrading
      enzyme involved in inactivation of catechol-estrogens. Its gene contains a
      functional valine to methionine substitution at codon 158. OBJECTIVE: The aim of
      our study was to determine whether this polymorphism is associated with bone
      parameters and fracture risk in elderly subjects. METHODS: COMT genotypes were
      determined using TaqMan allelic discrimination in 2515 men and 3554 women from
      the Rotterdam Study, a population-based cohort study of individuals aged 55 and
      older. Associations with bone mineral density (BMD) and bone loss were analyzed
      using ANOVA or analysis of covariance, whereas fracture risk was analyzed using
      Cox's proportional hazard regression analysis. COMT mRNA expression in three
      osteoblastic cell lines (SaOS, MG63, and SVHFO) was analyzed by RT-PCR. RESULTS:
      Male carriers of the Met(158) allele had an increased risk for osteoporotic
      fractures (hazard ratio = 1.6; 95% confidence interval, 1.0-2.4) and for
      fragility fractures (hazard ratio = 2.7; 95% confidence interval, 1.3-5.9), with
      evidence for a dominant effect. Adjustments for age, height, weight, and BMD did
      not change the risk estimates. In women, this association was weaker and not
      significant. BMD was not significantly associated with the variant in either men
      or women. COMT mRNA was expressed in all three osteoblastic cell lines tested.
      CONCLUSION: The COMT Val158Met polymorphism is associated with fracture risk in
      elderly men, through a mechanism independent of BMD.

PMID- 17504907
TI  - Loss of integrity of thyroid morphology and function in children born to mothers
      with inadequately treated Graves' disease.
AB  - CONTEXT: Central congenital hypothyroidism (CH-C) in neonates born to mothers
      with inadequately treated Graves' disease usually needs T(4) supplementation. The
      thyroid and its regulatory system have not yet been extensively studied after
      T(4) withdrawal, until we observed disintegrated thyroid glands in some patients.
      OBJECTIVE: The aim was to study the occurrence and pathogenesis of disintegrated
      thyroid glands in CH-C patients. DESIGN, SETTING, PATIENTS, PARTICIPANTS: Thyroid
      function was measured and thyroid ultrasound imaging was performed in 13 children
      with CH-C due to inadequately treated maternal Graves' disease after T(4)
      supplementation withdrawal (group Aa). In addition, thyroid ultrasound imaging
      was performed in six children with CH-C born to inadequately treated mothers with
      Graves' disease, in whom T(4) supplementation was not withdrawn yet (group Ab) or
      never initiated (group Ac), in six euthyroid children born to adequately treated
      mothers with Graves' disease (group B), and in 10 T(4)-supplemented children with
      CH-C as part of multiple pituitary hormone deficiency (group C). MAIN OUTCOME
      MEASURES: Thyroid function and aspect (volume, echogenicity, echotexture) were
      measured. RESULTS: In group A, five children had developed thyroidal
      hypothyroidism characterized by persistently elevated TSH concentrations and
      exaggerated TSH responses after TRH stimulation. In the majority of patients in
      groups A and C, thyroid echogenicity and volume were decreased, and echotexture
      was inhomogeneous. Thyroid ultrasound imaging was normal in group B children.
      CONCLUSIONS: Inadequately treated maternal Graves' disease not only may lead to
      CH-C but also carries an, until now, unrecognized risk of thyroid disintegration
      in the offspring as well. We speculate that insufficient TSH secretion due to
      excessive maternal-fetal thyroid hormone transfer inhibits physiological growth
      and development of the child's thyroid.

PMID- 17504908
TI  - Lifetime and 12-month prevalence of Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition disorders among older African Americans: findings from
      the National Survey of American Life.
AB  - OBJECTIVE: The purpose of this study was to estimate lifetime and 12-month
      prevalence of 13 psychiatric disorders for older African Americans. METHODS: Data
      are from the older African American subsample of the National Survey of American
      Life. Selected measures of lifetime and 12-month Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (DSM-IV) psychiatric disorders were
      examined (i.e., panic disorder, agoraphobia, social phobia, generalized anxiety
      disorder, obsessive compulsive disorder, posttraumatic stress disorder (PTSD),
      major depressive disorder, dysthymia, bipolar I and II disorders, alcohol
      abuse/dependence, and drug abuse/dependence). RESULTS: Twenty-three percent of
      older African Americans reported at least one lifetime disorder and 8.54%
      reported at least one 12-month disorder. Alcohol abuse, PTSD, and major
      depression were the most prevalent lifetime disorders. The most prevalent 12
      month disorders were PTSD, major depression, and social phobia. Age, sex,
      education, and region were significantly associated with the odds of having a
      lifetime disorder. CONCLUSION: This is the first study of prevalence rates of
      serious mental disorders for older African Americans based on a national sample.
      Demographic correlates of the prevalence of disorders are discussed with an
      emphasis on age and regional differences.

PMID- 17504909
TI  - Depressed mood, cognitive impairment, and survival in older people admitted to
      care homes in England.
AB  - OBJECTIVE: To investigate psychiatric morbidity, cognitive impairment,
      dependency, and survival in residents newly admitted to care homes. METHODS: A
      total of 308 older people were assessed using measures of cognitive impairment
      and depressive symptomatology, and interviewable residents completed a quality-of
      life interview. Dependency levels were assessed by interviews with staff and
      medication data were collected from home records. Follow-up assessments were
      carried out at five and nine months. A telephone follow-up approximately 12
      months later augmented the survival data. RESULTS: Of residents whose outcomes
      were known, 73% survived throughout the nine-month study period. Residents who
      died before the five-month follow-up had higher scores on the depression measure
      than those surviving longer. Reduced survival was predicted by greater dependency
      at baseline. Of 188 surviving residents, 63 (38%) were classified as depressed at
      baseline. Twenty-seven (43%) of the latter were still classed as depressed at
      five and nine months. Just 19% of residents rated as depressed at baseline were
      prescribed antidepressant medication, increasing to 26% at each follow-up. There
      was significant coexistence of cognitive impairment and depressive
      symptomatology. CONCLUSION: High levels of mortality, psychiatric morbidity, and
      chronicity of depressed mood among residents requires care homes to improve
      access to specialist resources such as geriatric consultation, old-age
      psychiatry, occupational therapy, and physiotherapy. Findings suggest that future
      care standards should include external factors, such as the extent of access to
      relevant specialist services for vulnerable older people.

PMID- 17504910
TI  - Subunit-specific contribution of pore-forming domains to NMDA receptor channel
      structure and gating.
AB  - N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that
      contribute to fundamental physiological processes such as learning and memory
      and, when dysfunctional, to pathophysiological conditions such as
      neurodegenerative diseases, stroke, and mental illness. NMDARs are obligate
      heteromultimers typically composed of NR1 and NR2 subunits with the different
      subunits underlying the functional versatility of NMDARs. To study the
      contribution of the different subunits to NMDAR channel structure and gating, we
      compared the effects of cysteine-reactive agents on cysteines substituted in and
      around the M1, M3, and M4 segments of the NR1 and NR2C subunits. Based on the
      voltage dependence of cysteine modification, we find that, both in NR1 and NR2C,
      M3 appears to be the only transmembrane segment that contributes to the deep (or
      voltage dependent) portion of the ion channel pore. This contribution, however,
      is subunit specific with more positions in NR1 than in NR2C facing the central
      pore. Complimentarily, NR2C makes a greater contribution than NR1 to the shallow
      (or voltage independent) portion of the pore with more NR2C positions in pre-M1
      and M3-S2 linker lining the ion-conducting pathway. Substituted cysteines in the
      M3 segments in NR1 and NR2C showed strong, albeit different, state-dependent
      reactivity, suggesting that they play central but structurally distinct roles in
      gating. A weaker state dependence was observed for the pre-M1 regions in both
      subunits. Compared to M1 and M3, the M4 segments in both NR1 and NR2C subunits
      had limited accessibility and the weakest state dependence, suggesting that they
      are peripheral to the central pore. Finally, we propose that Lurcher mutation
      like effects, which were identified in and around all three transmembrane
      segments, occur for positions located at dynamic protein-protein or protein-lipid
      interfaces that have state-dependent accessibility to methanethiosulfonate (MTS)
      reagents and therefore can affect the equilibrium between open and closed states
      following reactions with MTS reagents.

PMID- 17504911
TI  - Vesicular ATP is the predominant cause of intercellular calcium waves in
      astrocytes.
AB  - Brain astrocytes signal to each other and neurons. They use changes in their
      intracellular calcium levels to trigger release of transmitters into the
      extracellular space. These can then activate receptors on other nearby astrocytes
      and trigger a propagated calcium wave that can travel several hundred micrometers
      over a timescale of seconds. A role for endogenous ATP in calcium wave
      propagation in hippocampal astrocytes has been suggested, but the mechanisms
      remain incompletely understood. Here we explored how calcium waves arise and
      directly tested whether endogenously released ATP contributes to astrocyte
      calcium wave propagation in hippocampal astrocytes. We find that vesicular ATP is
      the major, if not the sole, determinant of astrocyte calcium wave propagation
      over distances between approximately 100 and 250 microm, and approximately 15 s
      from the point of wave initiation. These actions of ATP are mediated by P2Y1
      receptors. In contrast, metabotropic glutamate receptors and gap junctions do not
      contribute significantly to calcium wave propagation. Our data suggest that
      endogenous extracellular astrocytic ATP can signal over broad spatiotemporal
      scales.

PMID- 17504912
TI  - Counting sperm does not add up any more: time for a new equation?
AB  - Although sperm dysfunction is the single most common cause of infertility, we
      have poor methods of diagnosis and surprisingly no effective treatment (excluding
      assisted reproductive technology). In this review, we challenge the usefulness of
      a basic semen analysis and argue that a new paradigm is required immediately. We
      discuss the use of at-home screening to potentially improve the diagnosis of the
      male and to streamline the management of the sub-fertile couple. Additionally, we
      outline the recent progress in the field, for example, in proteomics, which will
      allow the development of new biomarkers of sperm function. This new knowledge
      will transform our understanding of the spermatozoon as a machine and is likely
      to lead to non-ART treatments for men with sperm dysfunction.

PMID- 17504913
TI  - Cytoplasmic dynein participates in meiotic checkpoint inactivation in mouse
      oocytes by transporting cytoplasmic mitotic arrest-deficient (Mad) proteins from
      kinetochores to spindle poles.
AB  - The present study was designed to investigate the localization and function of
      cytoplasmic dynein (dynein) during mouse oocyte meiosis and its relationship with
      two major spindle checkpoint proteins, mitotic arrest-deficient (Mad) 1 and Mad2.
      Oocytes at various stages during the first meiosis were fixed and immunostained
      for dynein, Mad1, Mad2, kinetochores, microtubules, and chromosomes. Some oocytes
      were treated with nocodazole before examination. Anti-dynein antibody was
      injected into the oocytes at germinal vesicle (GV) stage before the examination
      of its effects on meiotic progression or Mad1 and Mad2 localization. Results
      showed that dynein was present in the oocytes at various stages from GV to
      metaphase II and the locations of Mad1 and Mad2 were associated with dynein's
      movement. Both Mad1 and Mad2 had two existing states: one existed in the
      cytoplasm (cytoplasmic Mad1 or cytoplasmic Mad2), which did not bind to
      kinetochores, while the other bound to kinetochores (kinetochore Mad1 or
      kinetochore Mad2). The equilibrium between the two states varied during meiosis
      and/or in response to the changes of the connection between microtubules and
      kinetochores. Cytoplasmic Mad1 and Mad2 recruited to chromosomes when the
      connection between microtubules and chromosomes was destroyed. Inhibition of
      dynein interferes with cytoplasmic Mad1 and Mad2 transportation from chromosomes
      to spindle poles, thus inhibits checkpoint silence and delays anaphase onset.
      These results indicate that dynein may play a role in spindle checkpoint
      inactivation.

PMID- 17504914
TI  - Molecular evolution of the carboxy terminal region of the zona pellucida 3
      glycoprotein in murine rodents.
AB  - In mammals, before fertilization can occur, sperm have to bind to, and penetrate,
      the zona pellucida (ZP). In the laboratory mouse, which has been used as a model
      system for fertilization studies, sperm-ZP binding has been found to be mediated
      by a region at the carboxy terminal, encoded by exon 7 of the Zp3 gene. This
      region shows considerable interspecific sequence diversity with some evidence of
      adaptive evolution in mammals, suggesting that it may contribute to species
      specific sperm-ZP binding. However, in a previous study of sequence diversity of
      ZP3 of three species of Australian murine rodents, we found an identical protein
      sequence of the region encoded by exon 7. Here, we expand this earlier study to
      determine the sequence diversity of this region in 68 out of the 130 species of
      Australasian murine rodents. Maximum likelihood analyses, using representatives
      of both New Guinean and Australian taxa, provide evidence of positive selection
      at three codons adjacent to, or within, the putative combining-site for sperm of
      ZP3, but this was not evident when the analysis was restricted to the Australian
      taxa. The latter group showed low levels of both intra- and inter-generic
      sequence divergences in the region encoded by exon 7 of Zp3, with little evidence
      that this region contributes to species specificity of sperm-ZP binding. These
      findings suggest that the selective forces acting on the Zp3 exon 7 region during
      the evolution of the Australasian murine rodents have been variable, and that
      positive selection has only occurred in a few lineages.

PMID- 17504915
TI  - Temporal detection of caspase-3 and -7 in bovine in vitro produced embryos of
      different developmental capacity.
AB  - Embryo quality is most frequently evaluated at the blastocyst stage, although
      quality parameters further back along the developmental axis, such as early
      developmental kinetics or oocyte quality, can be equally valuable. Despite the
      fact that previous studies in bovine have linked oocyte diameter and early
      developmental kinetics with blastocyst formation and viability, their relation
      with the incidence of apoptosis during embryo development remains relatively
      unexplored. Therefore, we related non-invasive parameters of oocyte and embryo
      quality, such as embryo kinetics, embryo morphology, and oocyte diameter, to the
      incidence of apoptosis throughout embryo development using fluorescent detection
      of active caspase-3 and -7. First, bovine in vitro embryos were selected
      according to developmental kinetics and morphology at four set times during
      culture and subjected to fluorescent detection of active caspase-3 and -7.
      Caspase activity was significantly higher in slow developing embryos in
      comparison with fast cleavers (P < 0.05), but was not related to embryo
      morphology. Second, bovine oocytes were divided into three groups on the basis of
      oocyte diameter and the resulting embryos were used for staining at the same four
      set times. Caspase activity was significantly higher in embryos derived from
      growing oocytes compared with those of fully grown oocytes at 45, 80, and 117
      hours post-insemination (hpi; P < 0.05), but not at 168 hpi.

PMID- 17504916
TI  - Regulation of adiponectin and its receptors in rat ovary by human chorionic
      gonadotrophin treatment and potential involvement of adiponectin in granulosa
      cell steroidogenesis.
AB  - In mammals, adiponectin and its receptors (AdipoR1 and AdipoR2) mRNAs are
      expressed in various tissues. However, the cellular expression and the role of
      adiponectin system have never been investigated in rat ovary. Here, we report the
      presence of adiponectin, AdipoR1 and AdipoR2 in rat ovaries, and we have
      investigated its role in granulosa cells. Using RT-PCR and western blot, we show
      that the mRNAs and proteins for adiponectin, AdipoR1 and AdipoR2 are found in the
      ovaries. Immunohistochemistry localized adiponectin, AdipoR1 and AdipoR2 in theca
      interstitial T-I cells, corpus luteum, oocyte and less abundantly in granulosa
      cells. In the KGN human granulosa cell line, adiponectin mRNA and protein were
      undetectable; AdipoR2 was weakly expressed, whereas AdipoR1 was clearly present.
      Human chorionic gonadotrophin (hCG) injection (48 h) after pregnant mare serum
      gonadotrophin (PMSG) injection (24 h) in immature rats increased the level of
      adiponectin (protein) by about threefold (P < 0.05) and those of AdipoR1 by
      threefold (mRNA, P < 0.05) and 1.5-fold (protein, P < 0.05) in ovary, whereas the
      mRNA and protein levels of AdipoR2 were unchanged. Interestingly, hCG injection
      (48 h) after the PMSG treatment (24 h) decreased plasma adiponectin levels and
      increased insulin plasma levels. In vitro in primary rat granulosa cells, human
      adiponectin recombinant (5 microg/ml) in the presence or absence of follicle
      stimulating hormone (10(-8) M, 48 h) had no effect on the steroidogenesis.
      However, it increased progesterone secretion (P < 0.05) by about twofold and
      oestradiol production (P < 0.05) by about 1.6-fold in response to insulin-like
      growth factor-I (IGF-I) (10(-8) M). Furthermore, it improved IGF-I-induced IGF-I
      receptor-beta subunit tyrosine phosphorylation and ERK1/2 phosphorylation. In
      basal state, human adiponectin recombinant also increased rapidly but transiently
      the ERK1/2, p38 and Akt phosphorylations, whereas it increased more lately the
      adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation. Thus,
      AdipoR1 and AdipoR2 are regulated by hCG treatment in rat ovary and adiponectin
      enhances IGF-I-induced steroidogenesis in granulosa cells.

PMID- 17504917
TI  - Protein kinase C activity mediates LH-induced ErbB/Erk signaling in
      differentiated hen granulosa cells.
AB  - While there is accumulating evidence that mitogen-activated protein kinase/Erk
      and protein kinase C (PKC) signaling inhibits premature differentiation of
      granulosa cells in hen prehierarchal follicles, it has only recently been
      established that these signaling pathways play an important facilitory role in
      promoting steroidogenesis in differentiated granulosa cells from preovulatory
      follicles. The present studies were conducted with differentiated granulosa cells
      to establish the ability of LH to initiate PKC activity, and the subsequent
      requirement for PKC activity in promoting the ErbB/Erk signaling cascade that
      ultimately facilitates LH-induced progesterone production. Incubation of
      differentiated granulosa cells with LH increases PKC activity within 15 min, and
      latently promotes Erk phosphorylation (P-Erk) by 180 min. Inhibition of PKC
      activity with GF109203X attenuates LH- and 8-bromo-cAMP (8-br-cAMP)-induced P
      Erk, but not P-Erk promoted by an epidermal growth factor (EGF) family ligand
      (e.g., transforming growth factor alpha). Importantly, inhibition of PKC activity
      also blocks the LH-induced increase in the autocrine expression of mRNA encoding
      the EGF family ligands, such as EGF, amphiregulin, and betacellulin. Furthermore,
      inhibition of EGF ligand shedding at the level of the cell membrane using the
      matrix metalloprotease activity inhibitor, GM6001, prevents both LH- and 8-br
      cAMP-induced P-Erk and progesterone production. These findings provide evidence
      for a facilitory role of PKC and ErbB/Erk signaling in LH-induced progesterone
      production, place the requirement for PKC activation upstream of ErbB/Erk
      activity, and demonstrate for the first time in a non-mammalian vertebrate the
      requirement for PKC activity in LH-induced expression of EGF family ligands in
      granulosa cells.

PMID- 17504918
TI  - Phosphoprotein enriched in astrocytes-15 is expressed in mouse testis and
      protects spermatocytes from apoptosis.
AB  - Phosphoprotein enriched in astrocytes (PEA-15) is a 15 kDa acidic serine
      phosphorylated protein expressed in different cell types, especially in the CN.
      We initially detected the expression of PEA-15 in primary cultures of Sertoli
      cells. To assess the presence and localization of PEA-15 in the mouse testis, we
      studied the expression pattern of the PEA-15 protein by immunohistochemistry and
      mRNA by in situ hybridization. Both the protein and the mRNA of PEA-15 were
      localized in the cytoplasm of Sertoli cells, all types of spermatogonia, and
      spermatocytes up till zygotene phase of the meiotic prophase. Subsequently, with
      ongoing development of the spermatocytes, the expression decreased and was very
      low in the cytoplasm of diplotene spermatocytes. To analyze the possible role of
      PEA-15 in the developing testis, null mutants for PEA-15 were examined. As the
      PEA-15 C terminus contains residues for ERK binding, we studied possible
      differences between the localization of the ERK2 protein in wild type (WT) and
      PEA-15(-/-)mice. In the WT testis, ERK2 was localized in the cytoplasm of Sertoli
      cells, B spermatogonia, preleptotene, leptotene, and zygotene spermatocytes,
      whereas in the KO testis, ERK2 was primarily localized in the nuclei of these
      cells and only little staining remained in the cytoplasm. Moreover, in PEA-15
      deficient mice, significantly increased numbers of apoptotic spermatocytes were
      found, indicating an anti-apoptotic role of PEA-15 during the meiotic prophase.
      The increased numbers of apoptotic spermatocytes were not found at a specific
      step in the meiotic prophase.

PMID- 17504919
TI  - Expression of Wsb2 in the developing and adult mouse testis.
AB  - We present a detailed study of the expression pattern of WD repeat and SOCS box
      containing 2 (Wsb2) in mouse embryonic and adult gonads. Wsb2 was previously
      identified in a differential screen aimed at identifying the genes involved in
      male- and female-specific gonadal development. Wsb2 expression was analysed
      during mouse gonadogenesis by real-time PCR, whole-mount and section in situ
      hybridisation and immunofluorescence. Wsb2 mRNA expression was initially detected
      in gonads of both sexes from 11.5 days post coitum (dpc) until 12.0 dpc. By 12.5
      dpc and thereafter, Wsb2 expression rapidly decreased in the female, while
      persisting in the male gonads. In foetal, newborn and juvenile testes, Wsb2 mRNA
      and protein were readily detected in the seminiferous cords within both Sertoli
      and germ cells. Wsb2 mRNA was present in spermatogonia, spermatocytes and in
      Sertoli cells of the adult mouse testis. The differential expression of Wsb2 in
      male versus female embryonic gonads suggests some male-specific role in gonad
      development, and its expression in the first wave of spermatogenesis indicates a
      role in germ cells. Real-time analysis of adult mouse testis tubules cultured in
      the presence of the Hedgehog signalling inhibitor, cyclopamine, showed a
      downregulation of Wsb2 mRNA after treatment which suggests that Wsb2 may be a
      target of Hedgehog signalling.

PMID- 17504920
TI  - Participation of phosphatidyl inositol 3-kinase/protein kinase B and ERK1/2
      pathways in interleukin-1beta stimulation of lactate production in Sertoli cells.
AB  - Interleukin-1beta (IL1beta ) belongs to a set of intratesticular regulators that
      provide the fine-tuning of cellular processes implicated in the maintenance of
      spermatogenesis. The aim of the present study was to analyze the signaling
      pathways that may participate in IL1beta regulation of Sertoli cell function.
      Sertoli cell cultures from 20-day-old rat were used. Stimulation of the cultures
      with IL1beta showed increments in phosphorylated protein kinase B (PKB), P70S6K,
      and ERK1/2 levels. A phosphatidyl inositol 3-kinase (PI3K) inhibitor (wortmannin
      (W)), a mammalian target of rapamycin inhibitor (rapamycin (R)), and a MEK
      inhibitor (PD98059 (PD)) were utilized to evaluate the participation of PI3K/PKB,
      P70S6K, and ERK1/2 pathways in the regulation of lactate production by IL1beta .
      PD and W, but not R, decreased IL1beta-stimulated lactate production. The
      participation of these pathways in the regulation of glucose uptake and lactate
      dehydrogenase (LDH) A mRNA levels by IL1beta was also analyzed. It was observed
      that W decreased IL1beta-stimulated glucose uptake, whereas PD and R did not
      modify it. On the other hand, PD decreased the stimulation of LDH A mRNA levels
      by IL1beta , whereas W and R did not modify it. In summary, results presented
      herein demonstrate that IL1beta stimulates PI3K/PKB-, P70S6K-, and ERK1/2
      dependent pathways in rat Sertoli cells. Moreover, these results show that while
      IL1beta utilizes the PI3K/PKB pathway to regulate glucose transport, it utilizes
      the ERK1/2 pathway to regulate LDH A mRNA levels. This study reveals that IL1beta
      utilizes different signal transduction pathways to modify the biochemical steps
      that are important to regulate lactate production in rat Sertoli cells.

PMID- 17504921
TI  - Expression of ion transport-associated proteins in human efferent and epididymal
      ducts.
AB  - Appropriate intraluminal microenvironment in the epididymis is essential for
      maturation of sperm. To clarify whether the anion transporters SLC26A2, SLC26A6,
      SLC26A7, and SLC26A8 might participate in generating this proper intraluminal
      milieu, we studied the localization of these proteins in the human efferent and
      the epididymal ducts by immunohistochemistry. In addition, immunohistochemistry
      of several SLC26-interacting proteins was performed: the Na(+)/H(+) exchanger 3
      (NHE3), the Cl(-) channel cystic fibrosis transmembrane conductance regulator
      (CFTR), the proton pump V-ATPase, their regulator Na(+)/H(+) exchanger regulating
      factor 1 (NHERF-1), and carbonic anhydrase II (CAII). Our results show that
      SLC26A6, CFTR, NHE3, and NHERF-1 are co-expressed on the apical side of the
      nonciliated cells, and SLC26A2 appears in the cilia of the ciliated cells in the
      human efferent ducts. In the epididymal ducts, SLC26A6, CFTR, NHERF-1, CAII, and
      V-ATPase (B and E subunits) were co-localized to the apical mitochondria rich
      cells, while SLC26A7 was expressed in a subgroup of basal cells. SLC26A8 was not
      found in the structures studied. This is the first study describing the
      localization of SLC26A2, A6 and A7, and NHERF-1 in the efferent and the
      epididymal ducts. Immunolocalization of human CFTR, NHE3, CAII, and V-ATPase in
      these structures differs partly from previous reports from rodents. Our findings
      suggest roles for these proteins in male fertility, either independently or
      through interaction and reciprocal regulation with co-localized proteins shown to
      affect fertility, when disrupted.

PMID- 17504922
TI  - The expression of ovine placental lactogen, StAR and progesterone-associated
      steroidogenic enzymes in placentae of overnourished growing adolescent ewes.
AB  - Overnourishing pregnant adolescent sheep promotes maternal growth but reduces
      placental mass, lamb birth weight and circulating progesterone. This study aimed
      to determine whether altered progesterone reflected transcript abundance for StAR
      (cholesterol transporter) and the steroidogenic enzymes (Cyp11A1, Hsd3b and
      Cyp17). Circulating and placental expression of ovine placental lactogen (oPL)
      was also investigated. Adolescent ewes with singleton pregnancies were fed high
      (H) or moderate (M) nutrient intake diets to restrict or support placental
      growth. Experiment 1: peripheral progesterone and oPL concentrations were
      measured in H (n=7) and M (n=6) animals across gestation (days 7-140). Experiment
      2: progesterone was measured to mid- (day 81; M: n=11, H: n=13) or late gestation
      (day 130; M: n=21, H: n=22), placental oPL, StAR and steroidogenic enzymes were
      measured by qPCR and oPL protein by immunohistochemistry. Experiment 1: in H vs M
      animals, term placental (P<0.05), total cotyledon (P<0.01) and foetal size
      (P<0.05) were reduced. Circulating oPL and progesterone were reduced at mid-
      (P<0.001, P<0.01) and late gestation (P<0.01, P<0.05) and oPL detection was
      delayed (P<0.01). Experiment 2: placental oPL was not altered by nutrition. In
      day 81 H animals, progesterone levels were reduced (P<0.001) but not related to
      placental or foetal size. Moreover, placental steroidogenic enzymes were
      unaffected. Day 130 progesterone (P<0.001) and Cyp11A1 (P<0.05) were reduced in H
      animals with intrauterine growth restriction (H+IUGR). Reduced mid-gestation
      peripheral oPL and progesterone may reflect altered placental differentiation
      and/or increased hepatic clearance respectively. Restricted placental growth and
      reduced biosynthesis may account for reduced progesterone in day 130 H+IUGR ewes.

PMID- 17504923
TI  - Role of protein kinase Cbeta in rhythmic contractions of human pregnant
      myometrium.
AB  - To assess the role of protein kinase Cbeta (PKCbeta) in human myometrial
      contractions during pregnancy, we evaluated the effect of a PKCbeta inhibitor
      (LY333531) on the pregnant and nonpregnant myometrial contractions and compared
      the level of PKCbeta in the pregnant myometrium with that in the nonpregnant
      myometrium. The effects of LY333531 on the myometrial contractions were examined
      by measuring contractile activity (frequency and amplitude). PKCbeta in human
      myometrium was assessed at mRNA level using real-time PCR method. The
      characteristics of contractile activity were different between the pregnant and
      the nonpregnant myometrium. The amplitude of rhythmic contractions in the preterm
      and term myometrium was increased 2- to 2.5-fold when compared with that in the
      nonpregnant myometrium, but the frequency of rhythmic contractions was decreased
      by about half. LY333531 (10(-6) M) reduced the increased amplitude in the preterm
      and term myometrium by about 50%, and the inhibitory effects of LY333531 in the
      pregnant myometrium were significantly greater than that in the nonpregnant
      myometrium (about 50 vs 25%). However, the frequency in the pregnant and
      nonpregnant myometrium was not influenced by LY333531. Real-time PCR revealed a
      significant, five- to sevenfold increase in the expression of PKCbeta mRNA in the
      preterm and term myometrium when compared with the nonpregnant myometrium. These
      findings suggest that the increased amplitude of human myometrial contractions
      during pregnancy is related to the increased level of PKCbeta. A PKCbeta
      inhibitor may reduce preterm uterine contractions and prevent preterm delivery.

PMID- 17504924
TI  - Expression of small heat shock-related protein 20 (HSP20) in rat myometrium is
      markedly decreased during late pregnancy and labour.
AB  - The underlying mechanisms regulating uterine contractions during labour are still
      poorly understood. Heat shock protein 20 (HSP20) is known to be present at high
      levels in smooth muscle and implicated in muscle relaxation, but HSP20 expression
      in the myometrium is completely undetermined. Since HSP20 has been implicated in
      smooth muscle relaxation, we hypothesized that HSP20 would be highly expressed in
      the rat myometrium during early and mid-pregnancy when the myometrium is
      relatively quiescent. Northern blot analysis particularly demonstrated that HSP20
      mRNA detection was significantly decreased from day (d) 22 of pregnancy to 1-day
      post-partum (PP) compared with d6 (P < 0.05). HSP20 mRNA detection was also
      significantly decreased from d22 to d23 of gestation compared with non-pregnant
      (NP) samples. Immunoblot analysis showed that detection of HSP20 was
      significantly decreased at d23 compared with d12 and d15 (P < 0.05). HSP20
      detection also significantly decreased at PP compared with d15 (P < 0.05).
      Immunofluorescence analysis demonstrated that after d15, plasma membrane
      associated localization of HSP20 decreased markedly in both circular and
      longitudinal muscle layers. In addition, HSP20 was detectable near cell membranes
      at much higher levels in the longitudinal muscle layer of progesterone-treated
      pregnant rats (delayed labour) at all gestational time points examined, compared
      with controls. Our results demonstrate that HSP20 mRNA and protein are highly
      expressed during early and mid-pregnancy and then the expression markedly
      decreases during late pregnancy and labour. The observed patterns of HSP20
      expression are consistent with a potential role for HSP20 in facilitating
      myometrium quiescence during early and mid-pregnancy.

PMID- 17504925
TI  - Age as a determinant of reproductive success among captive female rhesus macaques
      (Macaca mulatta).
AB  - A retrospective analysis was performed on fertility outcomes among a colony of
      captive Indian rhesus monkeys. The analysis covered over 30 years and was based
      on 1443 females with a total of 11,453 pregnancies. Various determinants of
      fertility were assessed including birth rates, pregnancy loss, infant survival,
      interbirth intervals, and interval from last birth to death. Binary variables
      were analyzed with generalized linear models with random intercepts, while linear
      mixed models were used for analysis of continuous variables. Age of the dam was a
      significant factor in determining whether a pregnancy resulted in a birth and
      whether an infant survived the first 30 days with primiparous or older mothers
      being less likely to produce an infant surviving to that age. In contrast, sex
      proved to be the only significant factor in determining whether an infant lived
      to 1 year, with females being more likely to survive. The interval between births
      proved to be affected primarily by dam age, while the late death of an infant
      depressed the likelihood of an extended time interval between her last birth and
      her death. Overall, these results demonstrate that maternal age contributes
      significantly to a decline in fertility and older females can live relatively
      long periods following birth of their last infant.

PMID- 17504926
TI  - Hormonal profile and reproductive performance in lactation deficient (OFA hr/hr)
      and normal (Sprague-Dawley) female rats.
AB  - Lactation deficiency may have important consequences on infant health,
      particularly in populations of low socioeconomic status. The OFA hr/hr (OFA)
      strain of rats, derived from Sprague-Dawley (SD) rats, has deficient lactation
      and is a good model of lactation failure. We examined the reproductive
      performance and hormonal profiles in OFA and SD strains to determine the cause(s)
      of the lactation failure of the OFA strain. We measured hormonal (PRL, GH,
      gonadotropins, oxytocin, and progesterone) levels by RIA in cycling, pregnant,
      and lactating rats and in response to suckling. Dopaminergic metabolism was
      assessed by determination of mediobasal hypothalamic dopamine and
      dihydroxyphenylacetic acid (DOPAC) concentrations by HPLC and tyrosine
      hydroxylase expression by immunocytochemistry and western blot. OFA rats have
      normal fertility but 50% of the litters die of malnutrition on early lactation;
      only 6% of the mothers show normal lactation. The OFA rats showed lower
      circulating PRL during lactation, increased hypothalamic dopamine and DOPAC, and
      impaired milk ejection with decreased PRL and oxytocin response to suckling.
      Before parturition, PRL release and lactogenesis were normal, but dopaminergic
      metabolism was altered, suggesting activation of the dopaminergic system in OFA
      but not in SD rats. The number of arcuate and periventricular neurons expressing
      tyrosine hydroxylase was higher in SD rats, but hypothalamic expression of TH was
      higher in OFA rats at the end of pregnancy and early lactation. These results
      suggest that the OFA rats have impaired PRL release linked with an augmented
      dopaminergic tone which could be partially responsible for the lactational
      failure.

PMID- 17504927
TI  - Effect of pressure at primary drying of freeze-drying mouse sperm reproduction
      ability and preservation potential.
AB  - Freeze-dried spermatozoa are capable of participating in normal embryonic
      development after injection into oocytes and thus useful for the maintenance of
      genetic materials. We recently reported that long-term preservation of freeze
      dried mouse spermatozoa by conventional methods requires temperatures lower than 
      80 degrees C. Successful permanent preservation of mouse spermatozoa at much
      higher temperatures requires thorough investigation of the freeze-drying
      procedure. Thus, we examined the relationship between the pressure at primary
      drying and the preservation potential of freeze-dried mouse spermatozoa. Three
      different primary drying pressures were applied to evaluate the effect of
      pressure on freeze-dried spermatozoa under varying storage conditions and the
      rate of development measured. The developmental rate of embryos to the blastocyst
      stage from intracytoplasmic sperm injection by freeze-dried spermatozoa at
      pressures of 0.04, 0.37, and 1.03 mbar without storage were 59% (337/576), 71%
      (132/187), and 33% (99/302) respectively. When stored at 4 degrees C for 6
      months, the rate was 13% (48/367), 50% (73/145), and 36% (66/182) respectively.
      These results show that primary drying pressure is an influential factor in the
      long-term preservation of freeze-dried mouse spermatozoa.

PMID- 17504928
TI  - Methylation of the PTEN promoter defines low-grade gliomas and secondary
      glioblastoma.
AB  - Glioblastoma multiforme (GBM) can present as either de novo or secondary tumors
      arising from previously diagnosed low-grade gliomas. Although these tumor types
      are phenotypically indistinguishable, de novo and secondary GBMs are associated
      with distinct genetic characteristics. PTEN mutations, which result in activation
      of the phosphoinositide 3-kinase (PI3K) signal transduction pathway, are frequent
      in de novo but not in secondary GBMs or their antecedent low-grade tumors.
      Results we present here show that grade II astrocytomas, oligodendrogliomas, and
      oligoastrocytomas commonly display methylation of the PTEN promoter, a finding
      that is absent in nontumor brain specimens and rare in de novo GBMs. Methylation
      of the PTEN promoter correlates with protein kinase B (PKB/Akt) phosphorylation,
      reflecting functional activation of the PI3K pathway. Our results also
      demonstrate frequent methylation of the PTEN promoter in grade III astrocytomas
      and secondary GBMs, consistent with the hypothesis that these tumors arise from
      lower grade precursors. PTEN methylation is rare in de novo GBMs and is mutually
      exclusive with PTEN mutations. We conclude that methylation of the PTEN promoter
      may represent an alternate mechanism by which PI3K signaling is increased in
      grade II and III gliomas as well as secondary GBMs, a finding that offers new
      therapeutic approaches in these patients.

PMID- 17504929
TI  - Characterization of the amplicon on chromosomal segment 4q12 in glioblastoma
      multiforme.
AB  - A subset of glioblastomas (GBMs) carry gene amplifications on chromosomal segment
      4q12. To characterize this amplicon in detail, we analyzed a set of 100 samples
      consisting of 65 GBMs, 10 WHO grade III astrocytomas, 12 oligodendrogliomas, and
      13 glioma cell cultures. We applied multiplex ligation-dependent probe
      amplification to determine the gene dosage of PDGFRA, KIT, and KDR and the
      flanking genes USP46, RASL11B, LNX1, CHIC2, SEC3L1, and IGFBP7. The amplicon was
      highly variable in size and copy number and extended over a region of up to 5 Mb.
      Amplifications on 4q12 were observed in 15% of GBMs and 23% of GBM cell cultures
      but not in 22 other gliomas. We analyzed transcription and translation of some
      genes within this amplicon. Gene amplification generally correlated with high
      transcript levels but did not necessarily result in increased protein levels.
      However, we detected frequent expression of proteins encoded by PDGFRA, KIT, and
      KDR in GBMs and GBM cell cultures independent of the amplification status. Future
      treatment of GBM patients may include drugs targeting multiple kinases that are
      encoded by genes on chromosomal segment 4q12.

PMID- 17504930
TI  - Prospective study of cigarette smoking and adult glioma: dosage, duration, and
      latency.
AB  - Tobacco products are major contributors of exogenous N-nitroso compounds, a group
      of potent neurocarcinogens. Overall results from studies of smoking and brain
      tumors have been null, but have provided little information on duration, age at
      smoking initiation, and latency. We prospectively examined the relation between
      cigarette smoking and glioma risk among men and women in three large U.S. cohort
      studies: the Health Professionals Follow-up Study (HPFS), the Nurses' Health
      Study I (NHS), and NHS II. Information on smoking history was obtained at
      baseline (1986 for HPFS, 1976 for NHS, and 1989 for NHS II) and updated
      biennially through 2002 in the HPFS and the NHS and 2003 in the NHS II. We
      confirmed 110 incident gliomas among men and 255 gliomas among women during
      667,673 and 4,388,515 person-years of follow-up, respectively. Cox proportional
      hazard models were used to estimate incidence rate ratios and 95% confidence
      intervals between smoking and glioma risk adjusting for age, total meat intake,
      and alcohol and coffee consumption. Estimates from each cohort were pooled using
      a random-effects model after determining that there was no heterogeneity by sex.
      No association with glioma risk was observed between baseline or updated smoking
      status, intensity, duration, or age at smoking initiation among men and women.
      Furthermore, no association with glioma risk was observed after allowing for an
      induction period between smoking and glioma diagnosis. These findings provide
      strong evidence that cigarette smoking is not associated with an appreciably
      elevated risk of adult glioma.

PMID- 17504931
TI  - Preoperative thrombocytosis predicts poor survival in patients with glioblastoma.
AB  - Thrombocytosis, which is defined as a platelet count greater than 400
      platelets/nl, has been found to be an independent predictor of shorter survival
      in various tumors. Release of growth factors from tumors has been proposed to
      increase platelet counts. Preoperative platelet counts and other clinical and
      hematological parameters were reviewed from the records of 153 patients diagnosed
      between 1999 and 2004 with histologically confirmed glioblastoma in order to
      evaluate the prognostic significance of preoperative thrombocytosis in these
      patients. The relationship between thrombocytosis and survival was initially
      analyzed in all patients regardless of further therapy. Univariate log-rank tests
      showed that the median survival time of 29 patients with preoperative
      thrombocytosis (19%) was significantly shorter (4 months; 95% confidence interval
      [95% CI], 3-6 months) compared to 124 patients with normal platelet counts (11
      months; 95% CI, 8-13 months; p = 0.0006). Multivariate analysis (Cox proportional
      hazards model) confirmed preoperative platelet count, age, prothrombin time, and
      activated partial thromboplastin time to be prognostic factors of survival (all p
      < 0.05). In a subset of patients (only operated patients with radiation therapy
      with or without additional chemotherapy), survival was likewise significantly
      shorter when preoperative thrombocytosis was diagnosed (6 months; 95% CI, 4-12
      months) compared to patients with normal platelet count (13 months; 95% CI, 11-15
      months; p = 0.0359). In multivariate analysis, age, platelet count, preoperative
      prothrombin time, and degree of tumor resection retained significance as
      prognostic factors of survival (all p < 0.05). The results of our study
      demonstrate preoperative thrombocytosis to be a prognostic factor associated with
      shorter survival time in patients with glioblastoma.

PMID- 17504932
TI  - The A, B, Gs of silencing.

PMID- 17504933
TI  - YY1 helps to bring loose ends together.

PMID- 17504934
TI  - Expanding RNA physiology: microRNAs in a unicellular organism.

PMID- 17504935
TI  - Direct glucocorticoid receptor-Stat5 interaction in hepatocytes controls body
      size and maturation-related gene expression.
AB  - The glucocorticoid receptor regulates transcription through DNA binding as well
      as through cross-talk with other transcription factors. In hepatocytes, the
      glucocorticoid receptor is critical for normal postnatal growth. Using hepatocyte
      specific and domain-selective mutations in the mouse we show that Stat5 in
      hepatocytes is essential for normal postnatal growth and that it mediates the
      growth-promoting effect of the glucocorticoid receptor through a direct
      interaction involving the N-terminal tetramerization domain of Stat5b. This
      interaction mediates a selective and unexpectedly extensive part of the
      transcriptional actions of these molecules since it controls the expression of
      gene sets involved in growth and sexual maturation.

PMID- 17504936
TI  - Ipl1p-dependent phosphorylation of Mad3p is required for the spindle checkpoint
      response to lack of tension at kinetochores.
AB  - The spindle checkpoint delays anaphase onset until all chromosomes are correctly
      attached to microtubules. Ipl1 protein kinase (Aurora B) is required to correct
      inappropriate kinetochore-microtubule attachments and for the response to lack of
      tension between sister kinetochores. Here we identify residues in the checkpoint
      protein Mad3p that are phosphorylated by Ipl1p. When phosphorylation of Mad3p at
      two sites is prevented, the cell's response to reduced kinetochore tension is
      dramatically curtailed. Our data provide strong evidence for a distinct
      checkpoint pathway responding to lack of sister kinetochore tension, in which
      Ipl1p-dependent phosphorylation of Mad3p is a key step.

PMID- 17504937
TI  - Yin Yang 1 is a critical regulator of B-cell development.
AB  - The role of the transcription factor Yin Yang 1 (YY1) in development is largely
      unknown. Here we show that specific ablation of YY1 in mouse B cells caused a
      defect in somatic rearrangement in the immunoglobulin heavy-chain (IgH) locus and
      a block in the progenitor-B-to-precursor-B-cell transition, which was partially
      rescued by a prerearranged IgH transgene. Three-dimensional DNA fluorescence in
      situ hybridization analysis revealed an important function for YY1 in IgH locus
      contraction, a process indispensable for distal V(H) to D(H)J(H) recombination.
      We provide evidence that YY1 binds the intronic Ei mu enhancer within the IgH
      locus, consistent with a direct role for YY1 in V(H)D(H)J(H) recombination. These
      findings identified YY1 as a critical regulator of early B-cell development.

PMID- 17504938
TI  - The Prp18 protein stabilizes the interaction of both exons with the U5 snRNA
      during the second step of pre-mRNA splicing.
AB  - Interaction of the ends of the exons with loop 1 of the U5 snRNA aligns the exons
      for ligation in the second step of pre-mRNA splicing. To study the effect of
      Prp18 on the exons' interactions, we analyzed the splicing of pre-mRNAs with
      random sequences in the exon bases at the splice junctions. The exon mutations
      had large effects on splicing in yeast with a Prp18 protein lacking its most
      conserved region, but not in wild-type yeast. Analysis of splicing kinetics
      demonstrated that only the second step was affected in vivo and in vitro, showing
      that Prp18 - and specifically its conserved region - plays a key role in
      stabilizing the interaction of the exons with the spliceosome at the time of exon
      joining. Superior exon sequences defined by the prp18 results accelerated the
      second step of splicing by wild-type spliceosomes with inefficient AT-AC pre
      mRNAs, implying that normal exon interactions follow the rules we discerned for
      prp18 splicing. Our results show that As are preferred at the ends of both exons
      and support a revised model of the interactions of the exons with U5 in which the
      exons are arranged in a continuous double helix that facilitates the second
      reaction.

PMID- 17504939
TI  - Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon
      selection in vivo.
AB  - Selection of the AUG start codon is a key step in translation initiation
      requiring hydrolysis of GTP in the eIF2*GTP*Met-tRNA(i)(Met) ternary complex (TC)
      and subsequent P(i) release from eIF2*GDP*P(i). It is thought that eIF1 prevents
      recognition of non-AUGs by promoting scanning and blocking P(i) release at non
      AUG codons. We show that Sui(-) mutations in Saccharomyces cerevisiae eIF1, which
      increase initiation at UUG codons, reduce interaction of eIF1 with 40S subunits
      in vitro and in vivo, and both defects are diminished in cells by overexpressing
      the mutant proteins. Remarkably, Sui(-) mutation ISQLG(93-97)ASQAA (abbreviated
      93-97) accelerates eIF1 dissociation and P(i) release from reconstituted
      preinitiation complexes (PICs), whereas a hyperaccuracy mutation in eIF1A (that
      suppresses Sui(-) mutations) decreases the eIF1 off-rate. These findings
      demonstrate that eIF1 dissociation is a critical step in start codon selection,
      which is modulated by eIF1A. We also describe Gcd(-) mutations in eIF1 that
      impair TC loading on 40S subunits or destabilize the multifactor complex
      containing eIF1, eIF3, eIF5, and TC, showing that eIF1 promotes PIC assembly in
      vivo beyond its important functions in AUG selection.

PMID- 17504940
TI  - Gas1 extends the range of Hedgehog action by facilitating its signaling.
AB  - Cellular signaling initiated by Hedgehog binding to Patched1 has profound
      importance in mammalian embryogenesis, genetic disease, and cancer. Hedgehog acts
      as a morphogen to specify distinctive cell fates using different concentration
      thresholds, but our knowledge of how the concentration gradient is interpreted
      into the activity gradient is incomplete. The membrane protein Growth Arrest
      Specific Gene 1 (GAS1) was thought to be a negative regulator of the Hedgehog
      concentration gradient. Here, we report unexpected genetic evidence that Gas1
      positively regulates Hedgehog signaling in multiple developmental contexts, an
      effect particularly noticeable at regions where Hedgehog acts at low
      concentration. Using a combination of in vitro cell culture and in ovo
      electroporation assays, we demonstrate that GAS1 acts cooperatively with Patched1
      for Hedgehog binding and enhances signaling activity in a cell-autonomous manner.
      Our data support a model in which GAS1 helps transform the Hedgehog protein
      gradient into the observed activity gradient. We propose that Gas1 is an
      evolutionarily novel, vertebrate-specific Hedgehog pathway regulator.

PMID- 17504941
TI  - The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh
      signaling during mouse development.
AB  - Hedgehog (Hh) signaling is critical for patterning and growth during mammalian
      embryogenesis. Transcriptional profiling identified Growth-arrest-specific 1
      (Gas1) as a general negative target of Shh signaling. Data presented here define
      Gas1 as a novel positive component of the Shh signaling cascade. Removal of Gas1
      results in a Shh dose-dependent loss of cell identities in the ventral neural
      tube and facial and skeletal defects, also consistent with reduced Shh signaling.
      In contrast, ectopic Gas1 expression results in Shh-dependent cell-autonomous
      promotion of ventral cell identities. These properties mirror those of Cdo, an
      unrelated, cell surface Shh-binding protein. We show that Gas1 and Cdo cooperate
      to promote Shh signaling during neural tube patterning, craniofacial, and
      vertebral development. Overall, these data support a new paradigm in Shh
      signaling whereby positively acting ligand-binding components, which are
      initially expressed in responding tissues to promote signaling, are then down
      regulated by active Hh signaling, thereby modulating responses to ligand input.

PMID- 17504942
TI  - Environmental regulation operating at the promoter clearance step of bacterial
      transcription.
AB  - In vivo transcription of the Escherichia coli argO gene, which encodes an
      arginine (Arg) exporter, requires the LysR-family regulator protein ArgP
      (previously called IciA) and is induced in the presence of Arg or its naturally
      occurring antimetabolite analog canavanine. Lysine (Lys) addition, on the other
      hand, phenocopies an argP mutation to result in the shutoff of argO expression.
      We now report that the ArgP dimer by itself is able to bind the argO promoter
      operator region to form a binary complex, but that the formation of a ternary
      complex with RNA polymerase is greatly stimulated only in presence of a
      coeffector. Both Arg and Lys were proficient as coeffectors for ArgP-mediated
      recruitment of RNA polymerase to, and open complex formation at, the argO
      promoter, although only Arg (but not Lys) was competent to activate
      transcription. The two coeffectors competed for binding to ArgP, and the ternary
      complex that had been assembled on the argO template in the presence of Lys could
      be chased into a transcriptionally active state upon Arg addition. Our results
      support a novel mechanism of argO regulation in which Lys-bound ArgP reversibly
      restrains RNA polymerase at the promoter, at a step (following open complex
      formation) that precedes, and is common to, both abortive and productive
      transcription. This represents, therefore, the first example of an environmental
      signal regulating the final step of promoter clearance by RNA polymerase in
      bacterial transcription. We propose that, in E. coli cells, the ternary complex
      remains assembled and poised at the argO promoter at all times to respond,
      positively or negatively, to instantaneous changes in the ratio of intracellular
      Arg to Lys concentrations.

PMID- 17504943
TI  - Nodular regenerative hyperplasia in patients with inflammatory bowel disease
      treated with azathioprine.
AB  - AIM: To assess the characteristics and clinical course of nodular regenerative
      hyperplasia (NRH) in patients with inflammatory bowel disease treated with
      azathioprine, so as to estimate the frequency of this complication and search for
      risk factors. METHODS: Cases were identified through a systematic survey of
      patients followed at 11 centres. At one centre, the cumulative risk of NRH was
      estimated and a case-control study was undertaken to identify risk factors.
      RESULTS: 37 cases of NRH (30 male, 7 female) were identified between 1994 and
      2005. The median dose of azathioprine was 2 mg/kg/d (range 1.5 to 3.0). The
      median time between the start of azathioprine and the diagnosis of NRH was 48
      months (range 6 to 187). After a median follow up period of 16 months (range 1 to
      138), 14 patients developed complications of portal hypertension. Using
      multivariate analysis, male sex and stricturing behaviour were the two risk
      factors associated with NRH in patients treated with azathioprine. The cumulative
      risk calculated from the database (one centre) was 0.5% at 5 years (95%
      confidence interval, 0.11 to 0.89) and 1.25% at 10 years (0.29 to 2.21).
      CONCLUSIONS: NRH is a rare but potentially severe complication of azathioprine in
      patients with inflammatory bowel disease. Clinicians should be aware of this
      complication, and should monitor liver function tests and platelet counts closely
      in their patients.

PMID- 17504944
TI  - IgG4 associated autoimmune hepatitis: a differential diagnosis for classical
      autoimmune hepatitis.

PMID- 17504945
TI  - Suppression of osteoclastogenesis by N,N-dimethyl-D-erythro-sphingosine: a
      sphingosine kinase inhibition-independent action.
AB  - N,N-Dimethyl-D-erythro-sphingosine (DMS) competitively inhibits sphingosine
      kinase (SPHK) and has been widely used to assess the role of SPHK during cellular
      events, including motility, proliferation, and differentiation. In the present
      study, the effect of DMS on the differentiation of bone marrow macrophages (BMMs)
      to osteoclasts was investigated. When the osteoclast precursor cells were treated
      with DMS, the receptor activator of nuclear factor kappaB ligand (RANKL)-induced
      osteoclastogenesis was completely blocked. We were surprised to find, however,
      that knock-down of SPHK by small interfering RNA (siRNA) in BMMs did not reduce
      osteoclastogenesis. Furthermore, both overexpression of SPHK and exogenous
      addition of sphingosine-1-phosphate, the product of SPHK activity, failed to
      overcome the antiosteoclastogenic effect of DMS. These results suggest that DMS
      inhibited osteoclastogenesis independently of SPHK. Subsequent characterization
      of the DMS-mediated suppression of osteoclastogenesis revealed that DMS did not
      affect RANKL-induced activation of JNK, p38, NF-kappaB, and Ca2+ oscillation. On
      the other hand, DMS strongly inhibited two separate signaling pathways, the RANKL
      induced activation of ERK and Akt, which eventually converged on the
      transcription factors c-Fos and NFATc1. There was significant increase in the
      osteoclast formation in the presence of DMS when BMMs were overexpressed with c
      Fos, suggesting that c-Fos was a critical downstream target of DMS for the
      inhibition of osteoclastogenesis. Taken together, our data demonstrate that DMS
      has an antiosteoclastogenic function independently of its SPHK inhibitory
      activity. Considering previously reported anticancer properties of DMS, our study
      may also propose that DMS is an ideal drug candidate for bone metastases, for
      which osteoclastic bone-resorption is crucial.

PMID- 17504946
TI  - Glitazones induce astroglioma cell death by releasing reactive oxygen species
      from mitochondria: modulation of cytotoxicity by nitric oxide.
AB  - The glitazones (or thiazolidinediones) are synthetic compounds used in type-2
      diabetes, but they also have broad antiproliferative and anti-inflammatory
      properties still not well understood. We described previously the apoptotic
      effects of glitazones on astroglioma cells ( J Biol Chem 279: 8976-8985, 2004 ).
      At certain concentrations, we found a selective lethality on glioma cells versus
      astrocytes that was dependent on a rapid production of reactive oxygen species
      (ROS) and seemed unrelated to the receptor peroxisome proliferator activated
      receptor-gamma. The present study was aimed at characterizing the oxygen
      derivatives induced by ciglitazone, rosiglitazone, and pioglitazone in C6 glioma
      cells and to investigate their intracellular source. We examined the interaction
      of ROS with nitric oxide (NO) and its consequences for glioma cell survival.
      Fluorescence microscopy and flow cytometry showed that glitazones induced
      superoxide anion, peroxynitrite, and hydrogen peroxide, with ciglitazone being
      the most active. ROS production was completely prevented by uncoupling of the
      electron transport chain and by removal of glucose as an energy substrate,
      whereas it was unaffected by inhibition of NADPH-oxidase and xanthine-oxidase.
      Moreover, glitazones inhibited state 3 respiration in permeabilized cells, and
      experiments with mitochondrial inhibitors suggested that complex I was the likely
      target of glitazones. Therefore, these results point to the mitochondrial
      electron transport chain as the source of glitazone-induced ROS in C6 cells.
      Glitazones also depolarized mitochondria and reduced mitochondrial pH. NO
      synthase inhibitors revealed that superoxide anion combines with NO to yield
      peroxynitrite and that the latter contributes to the cytotoxicity of glitazones
      in astroglioma cells. Future antitumoral strategies may take advantage of these
      findings.

PMID- 17504947
TI  - A genome-scale map of expression for a mouse brain section obtained using
      voxelation.
AB  - Gene expression signatures in the mammalian brain hold the key to understanding
      neural development and neurological diseases. We have reconstructed two
      dimensional images of gene expression for 20,000 genes in a coronal slice of the
      mouse brain at the level of the striatum by using microarrays in combination with
      voxelation at a resolution of 1 mm3. Good reliability of the microarray results
      were confirmed using multiple replicates, subsequent quantitative RT-PCR
      voxelation, mass spectrometry voxelation, and publicly available in situ
      hybridization data. Known and novel genes were identified with expression
      patterns localized to defined substructures within the brain. In addition, genes
      with unexpected patterns were identified, and cluster analysis identified a set
      of genes with a gradient of dorsal/ventral expression not restricted to known
      anatomical boundaries. The genome-scale maps of gene expression obtained using
      voxelation will be a valuable tool for the neuroscience community.

PMID- 17504949
TI  - Evaluation of calving seasons and marketing strategies in Northern Great Plains
      beef enterprises. II. Retained ownership systems.
AB  - Two bioeconomic computer models were used to evaluate calving seasons in
      combination with calf marketing strategies for a range-based cow-calf enterprise
      in the Northern Great Plains. Calving seasons studied were spring (SP, calving
      beginning March 15 and weaning October 31), spring with calf mortality increased
      by 5% (SP-IM), summer (SU, calving beginning May 15 and weaning December 31),
      summer with early weaning (SU-EW, calving beginning May 15 and weaning October
      31), and fall (FA, calving beginning August 15 and weaning February 1). Marketing
      scenarios for steer calves and nonreplacement heifer calves were as follows: sold
      after weaning (WS), backgrounded in Montana and sold as feeder cattle (WBS),
      backgrounded in Montana and then fed to slaughter BW in Nebraska (WBFS), and
      shipped to Nebraska at weaning and fed to slaughter BW (WFS). Quarterly inflation
      adjusted cattle and feedstuff prices were representative of the 1990s cattle
      cycle. Cumulative gross margin (CGM), the sum of ranch gross margin and net
      return from retained ownership was used to compare systems. At the peak of the
      cattle cycle, all forms of retained ownership (WBS, WBFS, WFS) were profitable
      for all calving seasons, but during the descending phase, only WBS increased CGM
      markedly over WS for SU-EW. At the cycle valley, retained ownership was not
      profitable for SP and SP-IM, whereas WBFS and WFS were profitable for SU and SU
      EW, and all forms of retained ownership were profitable for FA. During the
      ascending phase, retained ownership was profitable for all calving season
      marketing combinations. Systems with the greatest CGM at each phase of the cattle
      cycle were FA-WFS, SP-WBS, FA-WFS, and FA-WFS at the peak, descending, valley,
      and ascending phases, respectively. In beef enterprises representative of the
      Northern Great Plains, with a restricted grazing season and limited access to low
      cost, good-quality grazeable forage, no single calving season and no single
      combination of calving season and calf marketing is expected to be superior
      throughout the cattle cycle. Fall calving systems most often benefit from
      retained ownership through slaughter.

PMID- 17504948
TI  - Dissection of a genetic locus influencing renal function in the rat and its
      concordance with kidney disease loci on human chromosome 1q21.
AB  - Previously, we conducted a genome scan on a population derived from the Dahl salt
      sensitive hypertensive (S) and the spontaneously hypertensive rat (SHR) using
      urinary albumin excretion (UAE) as our primary measure of renal function. We
      identified 10 quantitative trait loci (QTL) linked to several renal and/or
      cardiovascular traits. In particular, linkage and subsequent congenic strain
      analysis demonstrated that the loci on chromosome 2 had a large and significant
      effect on UAE compared with the S rat. The present work sought to characterize
      the chromosome 2 congenic strain [S.SHR] by conducting a time-course analysis
      (week 4-20), including evaluating additional renal parameters, histology,
      electron microscopy, and gene expression/ pathway analysis. Throughout the time
      course the congenic strain consistently maintained a threefold reduction in UAE
      compared with S rats and was supported by the histological findings of
      significantly reduced glomerular, tubular and interstitial changes. Gene
      expression/pathway analysis performed at week 4, 12, and 20 revealed that
      pathways involved in cellular assembly and organization, cellular movement, and
      immune response were controlled differently between the S and congenic. When all
      the data are considered, the chromosome 2 congenic appears to attenuate renal
      damage primarily through an altered fibrotic response. Recombinant progeny
      testing was employed to reduce the QTL to approximately 1.5 cM containing several
      interesting candidate genes. The concordance of this rat QTL with renal disease
      loci on human chromosome 1q21 demonstrate that elucidating the causative gene and
      mechanism of the rat QTL may be of particular importance for understanding kidney
      disease in humans.

PMID- 17504950
TI  - Influence of pressed beet pulp and concentrated separator by-product on intake,
      gain, efficiency of gain, and carcass composition of growing and finishing beef
      steers.
AB  - The objectives of this experiment were to determine a NE value for pressed beet
      pulp and the value of concentrated separator by-product (de-sugared molasses) as
      a ruminal N source in growing and finishing diets for beef cattle. One hundred
      forty-four cross-bred beef steers (282 +/- 23 kg of initial BW) were used in 2
      experiments (growing and finishing). A randomized complete block design was used,
      with a 3 x 2 factorial arrangement of treatments (level of pressed beet pulp and
      inclusion of concentrated separator by-product) for both studies. Steers were
      blocked by BW and allotted randomly to 1 of 6 treatments. In the growing study,
      the control diet contained 49.5% corn, 31.5% corn silage, 10.0% alfalfa hay, and
      9.0% supplement (DM basis). Pressed beet pulp replaced corn at 0, 20, or 40% of
      dietary DM, and concentrated separator by-product replaced corn and urea at 10%
      of dietary DM. The growing study lasted for 84 d. Initial BW was an average of 2
      d BW after a 3-d, restricted (1.75% of BW) feeding of 50% alfalfa hay and 50%
      corn silage (DM basis), and final BW was an average of 2-d BW after a 3-d,
      restricted (1.75% of BW) feeding of 31.5% corn silage, 10.0% alfalfa hay, 25.0%
      dry-rolled corn, 20.0% pressed beet pulp, 5.0% concentrated separator by-product,
      and 8.5% supplement (DM basis). After the growing study, the steers were weighed
      (415 +/- 32 kg), rerandomized, and allotted to 1 of 6 finishing diets. The
      control diet for the finishing study included 45% dry-rolled corn, 40% high
      moisture corn, 5% brome hay, 5% pressed beet pulp, and 5% supplement. Pressed
      beet pulp replaced high-moisture corn at 5.0, 12.5, and 20.0% of the dietary DM,
      and concentrated separator by-product replaced high-moisture corn and supplement
      at 10.0% of diet DM. Steers were slaughtered on d 83 or 98 of the study. In the
      growing study, the addition of pressed beet pulp to growing diets linearly
      decreased (P = 0.001) DMI and ADG and inclusion of 10% concentrated separator by
      product decreased (P = 0.001) G:F. Increased levels of pressed beet pulp in the
      finishing diets caused a linear decrease (P = 0.001) in ADG and tended (P = 0.06
      and 0.07 for kg/d and % of BW, respectively) to quadratically decrease DMI,
      whereas addition of concentrated separator by-product increased (P = 0.02 and
      0.001 for kg/d and % of BW, respectively) DMI. Apparent NEg of pressed beet pulp
      was 94.2% of that of corn in the growing study and 81.5% of that of corn in the
      finishing study.

PMID- 17504951
TI  - Evaluation of calving seasons and marketing strategies in Northern Great Plains
      beef enterprises: I. Cow-calf systems.
AB  - A bioeconomic computer model was used to evaluate alternate calving seasons in a
      cow-calf enterprise under range conditions representative of the Northern Great
      Plains. The simulated ranch utilized a rotational breeding system based on
      Hereford and Angus and had a fixed forage base (4,500 animal unit months of
      native range, 520 t of grass hay, and 183 t of alfalfa hay). Calving seasons
      studied were spring (SP, beginning March 15), summer (SU, beginning May 15), and
      fall (FA, beginning August 15). Weaning dates were October 31, December 15, and
      February 1, for SP, SU, and FA. The SP system was also simulated with a 5%
      increase in calf mortality (SP-IM), and SU with early weaning on October 31 (SU
      EW). Herd size for the fixed resource was 509, 523, 519, 560, and 609 cows
      exposed per year for SP, SP-IM, SU, SU-EW, and FA, respectively. Corresponding
      values for weight weaned per cow exposed were 206, 186, 193, 153, and 145 kg.
      Steer calves, nonreplacement heifer calves, and cull cows were sold at the time
      of weaning. Quarterly cattle and feed prices used were representative of the
      peak, descending, valley, and ascending phases of the 1990s cattle cycle adjusted
      for inflation. Estimates of ranch gross margin (gross returns minus variable
      costs) were greatest for SP, followed by SP-IM, SU, SU-EW, and FA, and the ranks
      were consistent across phases of the cattle cycle. Differences between ranch
      gross margin for SP-IM and SU were small. In beef enterprises representative of
      the Northern Great Plains, with a restricted grazing season, limited access to
      low-cost, high-quality grazeable forage, and with calves sold at weaning,
      switching from early spring to a summer or fall calving date is not expected to
      improve profitability. If delaying calving improves calf survival, then calving
      in early summer may be a competitive choice.

PMID- 17504952
TI  - Ergovaline-induced vasoconstriction in an isolated bovine lateral saphenous vein
      bioassay.
AB  - Ergovaline has been proposed as a toxic component of endophyte-infected tall
      fescue. As many of the symptoms of fescue toxicosis are a result of compromised
      circulation, the objective of this study was to examine the vasoconstrictive
      potentials of ergovaline and a more documented ergopeptine, ergotamine, using a
      bovine, lateral (cranial branch) saphenous vein bioassay. Segments of the cranial
      branch of the lateral saphenous vein (2 to 3 cm) were collected from healthy,
      mixed breed cattle (n = 12 and n = 5 for the ergovaline and ergotamine
      experiments, respectively) at local abattoirs. The veins were trimmed of excess
      fat and connective tissue, sliced into 2- to 3-mm cross sections, and suspended
      in a myograph chamber containing 5 mL of a modified Krebs-Henseleit, oxygenated
      buffer (95% O2 + 5% CO2; pH = 7.4; 37 degrees C). The tissue was allowed to
      equilibrate at 1 g of tension for 90 min before of the addition of treatments.
      Increasing doses of ergovaline (1x10(-11) to 1 x10(-4) M) or ergotamine (1 x10(
      11) to 1 x 10(-5) M) were administered every 15 min after buffer replacement.
      Contractile response data were normalized to a percentage induced by a reference
      dose of norepinephrine (1 x10(-4) M). Contractile responses of saphenous veins
      were similar for ergovaline and ergotamine. Initial contractile responses began
      at 1 x10(-8) M for both ergovaline and ergotamine (4.4 +/- 0.8% and 5.6 +/-1.1%,
      respectively). Vascular tension continued to increase as the alkaloid
      concentrations increased (maximums: 43.7 +/-7.1% at 1 x10(-5) M ergotamine; 69.6
      +/- 5.3% at 1 x10(-4) M ergovaline). Interestingly, ergovaline-induced
      contractions (1 x10(-4) M) were not reversed by repeated buffer replacement over
      a 105-min period. As previously shown with ergotamine, these results confirm that
      ergovaline is a potent vasoconstrictor. The resistance of an ergovaline-induced
      contraction to relaxation over an extended period of time suggests a potential
      for bioaccumulation of this ergopeptine alkaloid and may aid in understanding its
      toxicity within the animal.

PMID- 17504953
TI  - Number of fetuses and conceptus growth throughout gestation in lines of pigs
      selected for ovulation rate or uterine capacity.
AB  - Selection for 11 generations in swine for ovulation rate (OR) or uterine capacity
      (UC) resulted in 19.6% greater prenatal survival at term in UC compared with OR.
      Our objective was to characterize the number of fetuses throughout gestation in
      each line, including an unselected control (CO) line. Five hundred ninety-three
      gilts produced over 4 farrowing seasons were subjected to unilateral-hysterectomy
      ovariectomy at 160 d of age and mated within line at 280 d of age. Gilts were
      assigned within sire family to be slaughtered (+/- 2 d) at d 25, 45, 65, 85, or
      105 of gestation. Ovulation rate and number of live and dead fetuses were
      recorded for each pregnant gilt (n = 402). Fetal and placental weights were also
      recorded. Ovulation rate of OR line gilts (18.0 +/- 0.3 ova) exceeded (P < 0.001)
      CO and UC lines (15.0 +/- 0.3 and 14.0 +/- 0.3 ova, respectively). Line and
      gestational age interacted to affect number of live fetuses (P < 0.001). Least
      squares means for CO were 10.1, 8.3, 7.2, 6.7, and 7.3 live fetuses for d 25, 45,
      65, 85, and 105, respectively (average SE = 0.46 fetuses). Corresponding means
      for OR were 13.4, 8.3, 7.9, 6.5, and 6.7 live fetuses, respectively (average SE =
      0.44 fetuses). Means for UC were 10.2, 9.0, 8.5, 7.5, and 8.0 live fetuses,
      respectively (average SE = 0.47 fetuses). In each line, number of live fetuses at
      d 25 was approximately 72% of ovulation rate. Mortality to d 45 was greatest in
      OR, intermediate in CO, and least in UC. Reductions in live fetuses continued to
      occur from d 45 to 105, but line differences at d 45 were essentially maintained
      to d 105. Number of live fetuses in gilts at d 114 was estimated from each of the
      survival curves and predicted values of 7.0, 5.9, and 7.8 per uterine horn for
      CO, OR, and UC lines, respectively. Selection for uterine capacity improved fetal
      survival primarily during the time period between d 25 and 45. Relative growth
      rate coefficients throughout gestation for placental tissue indicated a change in
      rank of the line means, implicating a relative later growth pattern of placental
      tissue in the UC line.

PMID- 17504954
TI  - Intravaginal impedance and sexual behavior of ovariectomized goats given estrogen
      alone or in combination with progesterone.
AB  - Intravaginal impedance (IVI) fluctuates during the goat estrous cycle. To
      understand which ovarian steroids are responsible for IVI changes and whether IVI
      variations are associated with precopulatory and copulatory behaviors, 8
      ovariectomized females were assigned to 4 treatments in a 4 x 4 Latin square
      replicated over four 8-d periods. The treatments were as follows: progesterone
      plus estradiol-17beta (P4 + E2), oil plus estradiol-17beta (E2), progesterone
      plus oil (P4), or oil (OIL). Daily IVI measurements at the vagino-cervical
      junction were taken at 1 and 70 KHz. Progesterone was given on d 2 and 3.
      Estradiol was given in the evening of d 5. On d 1 to 8, goats were group-exposed
      to a sexually experienced male and observed for the expression of sexual
      behaviors. On d 6 and 7, IVI was less when goats received P4 + E2 or E2 compared
      with goats given P4 or OIL (P < 0.05). Impedance measured at 1 kHz tended to
      remain lower on d 8 in P4 + E2-treated females compared with those given P4 or
      OIL (P < 0.055). Like previous results, P4 + E2 or E2 treatment induced
      behavioral estrus; 5 of 8 P4 + E2-treated and 5 of 8 E2-treated females were
      sexually receptive on d 6. On d 7, although IVI remained low and 2 of 8 P4 + E2
      treated goats and 4 of 8 E2-treated goats remained sexually receptive, no
      additional females were in estrus. No IVI decreases and no estrous behavior were
      observed in goats given P4 or OIL. This experiment demonstrated that E2 initiates
      the periestrous drop in IVI, and P4 may delay baseline return.

PMID- 17504955
TI  - Marker-assisted selection for commercial crossbred performance.
AB  - Several studies have shown that selection of purebreds for increased performance
      of their crossbred descendants under field conditions is hampered by low genetic
      correlations between purebred and commercial crossbred (CC) performance. Although
      this can be addressed by including phenotypic data from CC relatives for
      selection of purebreds through combined crossbred and purebred selection (CCPS),
      this also increases rates of inbreeding and requires comprehensive systems for
      collection of phenotypic data and pedigrees at the CC level. This study shows
      that both these limitations can be overcome with marker-assisted selection (MAS)
      by using estimates of the effects of markers on CC performance. To evaluate the
      potential benefits of CC-MAS, a model to incorporate marker information in
      selection strategies was developed based on selection index theory, which allows
      prediction of responses and rates of inbreeding by using standard deterministic
      selection theory. Assuming a genetic correlation between purebred and CC
      performance of 0.7 for a breeding program representing a terminal sire line in
      pigs, CC-MAS was shown to substantially increase rates of response and reduce
      rates of inbreeding compared with purebred selection and CCPS, with 60 CC half
      sibs available for each purebred selection candidate. When the accuracy of marker
      based EBV was 0.6, CC-MAS resulted in 34 and 10% greater responses in CC
      performance than purebred selection and CCPS. Corresponding rates of inbreeding
      were 1.4% per generation for CC-MAS, compared with 2.1% for purebred selection
      and 3.0% for CCPS. For marker-based EBV with an accuracy of 0.9, CC-MAS resulted
      in 75 and 43% greater responses than purebred selection and CCPS, and further
      reduced rates of inbreeding to 1.0% per generation. Selection on marker-based EBV
      derived from purebred phenotypes resulted in substantially less response in CC
      performance than in CC-MAS. In conclusion, effective use of MAS requires
      estimates of the effect on CC performance, and MAS based on such estimates
      enables more effective selection for CC performance without the need for
      extensive pedigree recording and while reducing rates of inbreeding.

PMID- 17504956
TI  - Effects of dietary strong acid anion challenge on regulation of acid-base balance
      in sheep.
AB  - The acid-base status of the extracellular fluid is directly affected by the
      concentrations of strong basic cations and strong acid anions that are absorbed
      into the bloodstream from the diet. The objective of this study was to develop
      and characterize a model for dietary acid challenge in sheep by decreasing the
      dietary cation-anion difference (DCAD) using NutriChlor (HCl-treated canola
      meal), an anionic feed supplement. Ten fully fleeced sheep (Rideau-Arcott, 54.3
      +/- 6.7 kg of BW) were fed either a control supplement [200 g/d of canola meal,
      DCAD = 184 mEq/kg of DM, calculated as (Na+ + K+) - (Cl- + S2-)] or an anionic
      supplement (AS; 200 g/d of NutriChlor, DCAD = -206 mEq/kg of DM) offered twice
      daily at 0700 and 1100 in a randomized complete block design. The sheep were
      individually housed and limit-fed a basal diet of dehydrated alfalfa pellets (22%
      CP and 1.2 Mcal of NE(g)/kg, DM basis) at 1.1 kg of DM/d offered twice daily at
      1000 and 1300. Two days before the beginning of the experiment, the sheep were
      fitted with vinyl catheters (0.86-mm i.d., 1.32-mm o.d.) in the left jugular vein
      to facilitate blood sampling. Blood and urine samples were obtained daily from
      1100 to 1130 on d 1 through 9 and at 0700, 1000, 1300, 1600, and 1900 on d 10.
      Blood was analyzed for hematocrit, plasma pH, gases, strong ions, and total
      protein. Urine samples were analyzed for pH. The AS induced a nonrespiratory acid
      base disturbance associated with lower (P < 0.05) plasma pH (7.47 vs. 7.39),
      lower (P < 0.05) urine pH (8.13 vs. 6.09), and lower (P < 0.05) strong ion
      difference (42.5 vs. 39.5). The AS reduced (P < 0.05) the concentration of plasma
      glucose, base excess, and bicarbonate and increased (P < 0.05) the concentration
      of K+ and Cl-. Lowering DCAD increased (P < 0.05) Ca2+ concentrations in plasma
      by 13%. In conclusion, this dietary model successfully induced a significant acid
      base disturbance in sheep. Although the acidifying effects of negative DCAD in
      the diet may have short-term prophylactic effects of elevating the concentration
      of Ca2+ in plasma, negative DCAD may have detrimental effects on acid-base
      balance.

PMID- 17504957
TI  - Genetic evaluation in the presence of uncertain additive relationships. I. Use of
      phenotypic information to ascertain paternity.
AB  - A simulation was carried out to investigate the implementation of a genetic
      evaluation when the additive relationship matrix is not completely known due to
      the presence of uncertain paternity in the pedigree. Data were simulated and
      analyzed using a linear mixed model that included a fixed contemporary group
      effect plus random additive and residual effects. For the univariate scenario,
      either 1 or 2 records of a single trait with heritabilities of 33, 50, and 67%
      were used to compute the probability of being the true sire (PTS) of each
      candidate sire for a given offspring. One record of 3 correlated traits was used
      to compute PTS in a 3-trait scenario. A Bayesian procedure via Markov Chain Monte
      Carlo was used to carry out the implementation, in which the PTS was computed
      without the need to invert the relationship matrix. The average probability of
      the true sire being identified as such (PSA), as well as the percentage
      difference (PD) between PSA and an equal prior probability assigned to each
      candidate sire, were computed for the single and 3-trait scenarios. Using 1
      trait, PSA increased with an increase in heritability. When repeated records were
      considered, the PD was increased by 50 to 386% compared with using just 1 record
      per animal for the varying heritabilities and number of candidate sires,
      suggesting that phenotypic information was better able to discriminate among
      candidate sires when more than 1 record was used to determine PSA. Using 3
      correlated traits increased PD by 77 to 98% when compared with using 1 record of
      a trait with 67% heritability. Similarly, the PD was increased by 105 to 1,021%,
      when compared with using 1 record of a trait with 33% heritability. These results
      indicate that the probability of identifying the true sire increased when 3
      correlated traits were used to compute PSA. The correlations between true and
      predicted breeding values of 3 traits were increased by 6 to 7% for all animals
      and 64 to 89% for animals with unknown paternity in the pedigree when estimated
      probability of paternity was used as compared with equal prior probability
      assigned to each candidate sire. For traits such as birth weight and weaning
      weight, in which only 1 measurement is taken, the 3-trait scenario could result
      in more animals being assigned the true sire than if birth or weaning weight was
      used separately. Further research is needed to determine the performance of this
      methodology in field data as well as the potential implementation of this
      methodology in conjunction with molecular information.

PMID- 17504958
TI  - Effects of frequent out-of-feed events on growth performance of nursery and grow
      finish pigs.
AB  - Two experiments were conducted to evaluate effects of out-of-feed events on
      nursery and grow-finish pig performance. An out-of-feed event is a period of time
      that pigs do not have access to feed as a result of late feed delivery or
      bridging in bulk bins, feed lines, or feeders. In these studies, we created an
      out-of-feed event by removing the feeders from pens or preventing access to the
      feeder. In Exp. 1, 190 pigs (initially 6.4 +/- 1.6 kg and 21 +/- 3 d of age) were
      used in a 35-d growth study. Treatments involved a 20-h feed withdrawal for 1, 2,
      or 3 randomly selected times or a control treatment where feeders were never
      withdrawn. Feeders were withdrawn on d 11 for pigs with 1 out-of-feed event, d 8
      and 23 for pigs with 2 out-of-feed events, and d 9, 14, and 20 for pigs with 3
      out-of-feed events. There was a treatment (P < 0.06) effect only during weeks in
      which an out-of-feed event occurred. Growth rate was lower (P < 0.05) for pigs
      with 1 out-of-feed event (d 11) compared with control in the d 8 to 14 period.
      During the same period, those pigs with the first of 2 (d 8) or 3 (d 9) out-of
      feed events had intermediate ADG. In the d 15 to 21 period, only pigs with the
      second and third of 3 out-of-feed events (d 15 and 20) had lower growth
      performance compared with control pigs, whereas growth performance was similar to
      the control for those with 1 or 2 out-of-feed events. Pigs with 3 out-of-feed
      events had greater ADG and G:F (P < 0.05) compared with the other 3 treatments
      for the d 22 to 28 period. For the overall study (d 0 to 35), there were no
      differences (P > 0.86) in growth performance among pigs with 0, 1, 2, or 3 out-of
      feed events. In Exp. 2, 479 pigs (initially 41.6 +/- 4 kg) were used in an 85-d
      growth study. Treatments involved feed withdrawal (20 h) weekly for the duration
      of the study; feed withdrawn weekly from d 45 to 85; or a control treatment where
      pigs had access to feed for the duration of the experiment. Feed withdrawal
      occurred on a randomly selected day with the exception of Saturday, Sunday, or a
      day before a weigh day (usually a Thursday every other week). From d 0 to 45, 46
      to 85, and the overall d 0 to 85 period, there were no differences (P > 0.12) in
      ADG, ADFI, G:F, or average final BW among treatments. Results suggest that out-of
      feed events of 20 h or less have no long-term detrimental effects on growth
      performance in nursery or grow-finish pigs.

PMID- 17504959
TI  - Bovine respiratory disease in feedlot cattle: phenotypic, environmental, and
      genetic correlations with growth, carcass, and longissimus muscle palatability
      traits.
AB  - Bovine respiratory disease (BRD) is the most costly feedlot disease in the United
      States. Selection for disease resistance is one of several possible interventions
      to prevent or reduce the economic loss associated with animal disease and to
      improve animal welfare. Undesirable genetic relationships, however, may exist
      between production and disease resistance traits. The objectives of this study
      were to estimate the phenotypic, environmental, and genetic correlations of BRD
      with growth, carcass, and LM palatability traits. Health records on 18,112
      feedlot cattle over a 15-yr period and slaughter data on 1,627 steers over a 4-yr
      period were analyzed with bivariate animal models. Traits included ADG, adjusted
      carcass fat thickness at the 12th rib, marbling score, LM area, weight of retail
      cuts, weight of fat trim, bone weight, Warner-Bratzler shear force, tenderness
      score, and juiciness score. The estimated heritability of BRD incidence was 0.08
      +/- 0.01. Phenotypic, environmental, and genetic correlations of the observed
      traits with BRD ranged from -0.35 to 0.40, -0.36 to 0.55, and -0.42 to 0.20,
      respectively. Most correlations were low or negligible. The percentage of carcass
      bone had moderate genetic, phenotypic, and environmental correlations with BRD (
      0.42, -0.35, and -0.36, respectively). Hot carcass weight and weight of retail
      cuts had moderate, undesirable phenotypic correlations with BRD (0.37 and 0.40,
      respectively). Correlations of BRD with LM palatability and ADG were not
      detected. Low or near zero estimates of genetic correlations infer that selection
      to reduce BRD in feedlot cattle would have negligible correlated responses on
      growth, carcass, and meat palatability traits or that selection for those traits
      will have little effect on BRD susceptibility or resistance.

PMID- 17504960
TI  - Livestock welfare product claims: the emerging social context.
AB  - An increasing number of product claims about food animal welfare or well-being
      have appeared in the global food industry and global market in recent years.
      These claims have significant consequences for producers, processors,
      transporters, retailers, consumers, and the animals themselves. Furthermore,
      recent restructuring of the global food industry has altered the power
      relationships of various actors. Regulation of the industry is moving toward
      greater private control, and the power of retailers has dramatically increased.
      The changing structure of the industry carries implications both in terms of how
      standards are created and in terms of the types of standards themselves. The
      purpose of this article is to provide a greater understanding of how these
      product claims are made, their implications, and the challenges they present.

PMID- 17504961
TI  - Response to ractopamine-HCl in heifers is altered by implant strategy across days
      on feed.
AB  - Two experiments were conducted to investigate the effects of ractopamine-HCl
      (RAC) and implant strategy or days on feed (DOF) on feedlot performance and
      expression of beta-adrenergic receptors (AR). In Exp. 1, 1,147 feedlot heifers
      weighing 282 +/- 3 kg were used with implant treatments of Revalor-200 (R200) at
      arrival, or Revalor-IH at arrival with reimplantation with Finaplix-H on d 58
      (RF). Ractopamine (0 vs. 200 mg/d) was fed the last 28 d in both experiments.
      Treatments were randomly assigned to 16 pens. At slaughter, semimembranosus
      muscle tissue was excised for RNA isolation. Ractopamine administration increased
      (P < 0.05) ADG, G:F, HCW, and LM; decreased (P < 0.05) 12th rib fat depth; and
      improved (P < 0.05) yield grade. There was no effect (P > 0.10) on the expression
      of beta1-AR mRNA; however, there was a tendency (P = 0.10) for RAC feeding to
      increase beta2-AR mRNA levels. For beta3-AR mRNA, there was an implant by RAC
      interaction (P = 0.05), with RAC numerically increasing beta3-AR mRNA in heifers
      implanted with RF, but a decrease (P < 0.05) in expression in heifers implanted
      with R200. Ractopamine also decreased (P < 0.05) IGF-I mRNA in heifers implanted
      with RF. In Exp. 2, 2,077 heifers were used to investigate the effects of RAC and
      DOF. Days on feed were 129, 150, and 170, and RAC was administered the last 28 d.
      Ractopamine improved (P < 0.05) G:F, but had no other effects (P > 0.05) on
      performance. Average daily gain decreased (P < 0.05) as DOF increased. Hot
      carcass weight, LM area, 12th rib fat, G:F, calculated yield grade, and marbling
      score increased (P < 0.05) and the percentage of KPH fat decreased (P < 0.05) as
      DOF increased. These data aid in our understanding of the effects of steroidal
      implants, DOF, and RAC administration in feedlot heifers.

PMID- 17504962
TI  - Prediction of nitrogen excretion in feces and urine of beef cattle offered diets
      containing grass silage.
AB  - Data from 286 beef cattle, obtained in total diet digestibility assessments, were
      used to examine effects of dietary and animal factors on N excretion in feces and
      urine and to develop prediction equations for N excretion in beef cattle. The
      animals used were mainly from beef breeds, at various ages (from growth to
      finishing) and live BW (153 to 580 kg), and offered diets containing grass silage
      at production feeding levels. Dietary forage proportion ranged from 199 to 1,000
      g/kg of DM and dietary CP concentration from 108 to 217 g/kg of DM. Linear and
      multiple regression techniques were used to examine relationships between the
      efficiency of N utilization and dietary and animal variables with the
      experimental effects removed. The statistical analysis indicated that N excretion
      was related positively (P < 0.001) to live BW and intakes of DM, N, and ME, and
      negatively (P < 0.001) to dietary forage proportion. The prediction equation for
      N excretion, developed using N intake alone, produced a large r2 (0.898) and a
      small SE (12.3). Addition of live BW and forage proportion as supporting
      predictors to this relationship only marginally increased R2 to 0.915 and reduced
      SE to 11.2. Nitrogen excretion was less well related to live BW (r2 = 0.771, SE =
      18.5) than to N intake. Addition of N intake as a proportion of DMI or ME intake
      to the relationship between live BW and N excretion increased R2 to 0.824 and
      reduced SE to 16.2. The internal validation of these equations revealed that
      using N intake as the primary predictor produced a very accurate prediction of N
      excretion. In situations where data on N intake are not available, prediction
      equations based on live BW and dietary N concentration together can produce a
      relatively accurate assessment of N excretion. A number of mitigation strategies
      to reduce N excretion in feces and urine in beef cattle are discussed, including
      manipulation of dietary N concentration, diet quality, and level of feeding. The
      prediction equations and mitigation strategies developed in the current study
      provide an approach for beef producers to quantify N excretion against production
      and to develop their own mitigation strategies to reduce N excretion.

PMID- 17504963
TI  - Energy and protein requirements for growth and maintenance of F1 Nellore x Red
      Angus bulls, steers, and heifers.
AB  - A comparative slaughter trial was conducted with 36 F1 Nellore x Red Angus calves
      (12 steers, 12 bulls, and 12 heifers), averaging 274 kg of BW, to assess the net
      requirements of protein and energy for growth and maintenance. Three cattle from
      each group (i.e., steers, bulls, and heifers) were slaughtered at the beginning
      of the trial to determine the initial body composition. The remaining calves were
      randomly assigned to 1 of 3 treatments: maintenance (diet containing 70% of DM as
      corn silage fed at 1.2% of BW daily) or concentrate at 0.75 or 1.5% of BW daily
      with corn silage available for ad libitum consumption. The diets were
      isonitrogenous (2% N, DM basis). The experimental design provided ranges in ME
      intake, BW, and ADG for the development of regression equations to predict the
      maintenance requirements for NE and net protein (MRNE and MRNP, respectively) and
      the growth requirement for NE and net protein (GRNE and GRNP, respectively).
      After 84 d of growth, the cattle were slaughtered. The cleaned gastrointestinal
      tracts, organs, carcasses, heads, hides, tails, feet, blood, and tissues were
      weighed to measure empty BW (EBW). These parts were ground separately and
      subsampled for chemical analyses. For each animal within a period, DMI was
      measured daily and samples of feces were collected to determine diet
      digestibility. There were no differences in MRNE (P = 0.06) among groups. The
      combined data indicated a MRNE of 71.2 kcal x kg(-0.75) of EBW x d(-1), with a
      partial efficiency of use of ME to NE(m) of 0.71. The partial efficiency of use
      of ME to NE for growth was 0.54 for bulls, 0.47 for steers, and 0.54 for heifers.
      The GRNE for steers and heifers were similar (P = 0.15) but were 18.7% greater (P
      = 0.03) for steers and heifers than for bulls. The MRNP did not differ among
      groups and averaged 2.53 g of CP x kg(-0.75) of EBW x d(-1). Likewise, GRNP was
      not different among groups. The percentage of retained energy deposited as
      protein (RE(p)) increased as the content of retained energy in the gain (RE(c),
      Mcal/kg of empty body gain) decreased. The RE(p) equation of the pooled data was
      46.5 x e(-0.2463 x RE(c)). We conclude that the energy requirement of crossbred
      Bos indicus x Bos taurus for maintenance might be less than that of purebred Bos
      taurus and that RE(p) is nonlinearly, negatively correlated with RE(c). The GRNE
      was less for bulls than for steers and heifers. However, we found no differences
      in MRNE, MRNP, and GRNP for bulls, steers, and heifers of Nellore x Red Angus
      crossbreds.

PMID- 17504964
TI  - Characterization of transport systems for cysteine, lysine, alanine, and leucine
      in wool follicles of sheep.
AB  - Aspects of the uptake of the AA Cys, Leu, Ala, and Lys into wool follicles were
      investigated using short-term culture of thin strips of sheep skin. Following
      verification of the reliability of the model system, the sites of uptake of the
      radiolabeled AA were shown to differ and to be consistent with their different
      roles in fiber production. Cysteine appeared in the zone of keratinization
      immediately distal to the follicle bulb. Lysine was incorporated into the
      germinative cells of the follicle bulb and the cells of the inner root sheath.
      Leucine and Ala were incorporated into the follicle bulb, inner root sheath, and
      keratinizing fiber. The incorporation of all AA into the dermal papilla was low.
      The relative rates of uptake of the AA into the wool follicle were as follows: L
      Cys (100), L-Leu (5.5), L-Ala (2.5), and L-Lys (0.8). Uptake of Cys was saturable
      and followed Michaelis-Menten kinetics, suggesting a carrier-mediated system,
      with little or no diffusion. The majority (70%) of Cys uptake into follicles was
      via a Na-independent system that was not inhibited by alpha-(methyl
      amino)isobutyric acid or 2-amino-2-norbonanecarboxylic acid and therefore is not
      via the normal Cys transport systems A, ASC, or L. Uptake of Cys appeared to be
      via a low-affinity, high-capacity transport system, which may be unique to the
      fiber-producing follicle. The majority of Ala transport had characteristics
      consistent with the functioning of system A (Na-dependent, inhibited by alpha
      (methylamino)isobutyric acid, and low substrate affinity). Leucine uptake was
      inhibited by 2-amino-2-norbonanecarboxylic acid but was Na-dependent, suggesting
      that a variant of system L operates in the follicle to transport Leu. Lysine
      uptake was consistent with the operation of the usual Lys transporter system y+.
      Diets designed to maximize wool growth should provide AA profiles reflecting the
      relative rates of uptake demonstrated in this study. Investigations of possible
      polymorphisms in genes encoding AA transport proteins in follicles may reveal a
      source of genetic differences in wool growth potential among genotypes.

PMID- 17504965
TI  - Dietary fish oil supplementation affects serum fatty acid concentrations in
      horses.
AB  - Thirteen horses of Thoroughbred or Standardbred breeding were used to study the
      effect of dietary fish oil supplementation on blood lipid characteristics. Horses
      were assigned to either fish oil (n = 7) or corn oil (n = 6) treatment groups for
      63 d. The fish oil contained 10.8% eicosapentaenoic acid (EPA) and 8%
      docosahexaenoic acid (DHA). Each horse received timothy hay and a mixed-grain
      concentrate at rates necessary to maintain BW. Oil (corn or fish) was top-dressed
      on the concentrate daily at a rate of 324 mg/ kg of BW. The n-6:n-3 ratio was
      approximately 3.6:1 for horses receiving the corn oil diet and 1.4:1 for horses
      receiving the fish oil diet. Horses were exercised 5 d/wk during the study.
      Before supplementation, there was no difference in the concentrations of any
      serum fatty acids between the 2 treatment groups. The mean basal concentrations
      of EPA and DHA on d 0 were 0.04 and 0.01 mg/mL, respectively. After 63 d, horses
      receiving the fish oil treatment, but not those receiving the corn oil treatment,
      had increased concentrations of EPA and DHA (P <0.05). Fish oil supplementation
      for 63 d also increased the concentrations of C22:0, C22:1, and C22:5 fatty acids
      (P <0.05). Overall, horses receiving fish oil had a decreased concentration of n
      6 fatty acids (P <0.05) and a greater concentration of n-3 fatty acids (P <0.01),
      resulting in a lower n-6:n-3 fatty acid ratio after 63 d (P <0.05). Serum
      cholesterol concentrations increased (P <0.05) during the supplementation period
      in horses receiving the corn oil but not in horses receiving the fish oil.
      Compared with horses receiving corn oil, horses receiving fish oil had lower
      serum triglycerides at d 63 (P <0.05). These results demonstrate that 63 d of
      fish oil supplementation at 324 mg/kg of BW was sufficient to alter the fatty
      acid profile and blood lipid properties of horses receiving regular exercise.

PMID- 17504966
TI  - The in vitro reduction of sodium [36Cl]chlorate in bovine ruminal fluid.
AB  - Sodium chlorate effectively reduces or eliminates gram-negative pathogenic
      bacteria in the gastrointestinal tracts of live cattle. Limitations to the in
      vivo efficacy of chlorate are its rapid absorption from the gastrointestinal
      tract and its presumed reduction to chloride within the gastrointestinal tract.
      We hypothesized that chlorate would be reduced via ruminal bacteria in a ruminal
      in vitro system and that the reduction of chlorate would be influenced by the
      dietary for-age:concentrate ratio; thus, 4 ruminally cannulated steers were fed
      20 or 80% concentrate diets in a crossover design. Ruminal fluid was collected in
      2 periods and dispensed into in vitro tubes containing sodium [36Cl]chlorate,
      which was sufficient for 100 or 300 mg/L final chlorate concentrations. The tubes
      were incubated for 0, 1, 4, 8, 16, or 24 h; autoclaved, control ruminal fluid,
      fortified with sodium [36Cl]chlorate, was incubated for 24 h. Chlorate remaining
      in each sample was measured by liquid scintillation counting after [36Cl]chloride
      was precipitated with silver nitrate. A preliminary study indicated that
      chlorite, a possible intermediate in the reduction of chlorate, had a half-life
      of approximately 4.5 min in freshly collected (live) ruminal fluid; chlorite was,
      therefore, not specifically measured in ruminal incubations. The chlorate dose
      did not affect in vitro DM digestion (P > or = 0.11), whereas in vitro DM
      digestibility was decreased (P < or = 0.05) by 80% forage content. By 24 h, 57.5
      +/- 2.6% of the chlorate remained in 100-mg/L incubations, whereas 78.2 +/- 2.6%
      of the chlorate remained in the 300-mg/L incubations. When the data were
      expressed on a concentration basis (mg/L), diet had no effect (P > or = 0.18) on
      chlorate reduction; however, when chlorate reduction was expressed on a
      percentage basis, chlorate reduction tended to be greater (P > or = 0.09) at 8
      and 16 h in the incubations containing the low-concentrate diet. Chlorate
      remaining in autoclaved controls at 24 h was intermediate (P < 0.01) between
      chlorate remaining in live ruminal fluid samples incubated for 0 or 24 h.
      Attempts to isolate chlorate-respiring bacteria from 2 sources of ruminal fluid
      were not successful. These data indicate that microbial-dependent or chemical
      dependent, or both, reduction of chlorate occurs in bovine ruminal fluid and that
      dietary concentrate had a negligible effect on chlorate reduction.

PMID- 17504967
TI  - Effect of dietary lactoferrin on the immune functions and serum iron level of
      weanling piglets.
AB  - A total of 90 weanling female pigs (Duroc x Landrace x Yorkshire) were used in a
      30-d growth experiment to investigate the effect of lactoferrin (LF) on growth
      performance, immune function, and serum iron concentrations. The pigs were
      allocated on the basis of BW and litter to 3 dietary treatments in a randomized
      complete block design. The dietary treatments were: control group (basal diet),
      antibiotics group (basal diet + 20 mg/kg of flavomycin + 110 mg/kg of
      aureomycin), and LF group (basal diet + 1.0 g/kg of LF). There were 3 replicate
      pens per treatment, and pigs were grouped with 10 pigs per pen. Six pigs,
      randomly selected from each treatment (2 pigs/pen), were slaughtered for serum
      and spleen samples on d 15 and 30. Supplementation with LF improved the
      phytohemagglutinin (PHA)-stimulated peripheral lymphocyte proliferation by 36% (P
      < 0.01), increased concanavalin A (ConA)- and PHA-induced spleen lymphocyte
      proliferation by 332% (P < 0.01) and 258% (P < 0.01), enhanced serum IgG by 20%
      (P < 0.05), IgA by 13% (P < 0.05), IgM by 15% (P < 0.05), complement 4 (C4) by
      29% (P < 0.05), IL-2 by 12% (P < 0.01), and serum iron values by 22% (P < 0.05)
      on d 15 compared with the control. Lactoferrin supplementation increased PHA
      stimulated lymphocyte proliferation (P < 0.01), serum IgG by 16% (P < 0.05), IgA
      by 17% (P < 0.05), C4 by 11% (P < 0.05), IL-2 by 14% (P < 0.05), and serum iron
      values by 23% (P < 0.01), and decreased the diarrhea ratio (P < 0.05) relative to
      the control on d 30. Compared with the controls, supplementation with antibiotic
      increased ConA- and PHA-induced spleen lymphocyte proliferation (P < 0.05) on d
      15, decreased the diarrhea ratio (P < 0.05), and increased the PHA-induced spleen
      lymphocyte proliferation (P < 0.05) and serum iron values (P < 0.01) on d 30.
      These results support the possible use LF as an immunostimulant to improve immune
      functions and strengthen host defenses and would seem to be a good method for
      defending weanling piglets from infections and weanling stress.

PMID- 17504968
TI  - Fertility traits in spring-calving Aberdeen Angus cattle. 1. Model development
      and genetic parameters.
AB  - Calving records (n = 6,763) obtained from first, second, and third parities of
      3,442 spring-calving, Uruguayan Aberdeen Angus cows were used to estimate
      heritabilities and genetic correlations for the linear trait calving day (CD) and
      the binary trait calving success (CS), using models that considered CD and CS at
      3 calving opportunities as separate traits. Three approaches were defined to
      handle the CD observations on animals that failed to calve: 1) the cows were
      assigned a penalty value of 21 d beyond the last observed CD record within
      contemporary group (PEN); 2) the censored CD values were randomly obtained from a
      truncated normal distribution (CEN); and 3) the CD records were treated as
      missing, and the parameters were estimated in a joint threshold-linear analysis
      including CS traits (TLMISS). The models included the effects of contemporary
      group (herd x year of calving x mating management), age at calving (3 levels),
      physiological status at mating (nonlactating or lactating), animal additive
      genetic effects, and residual. Estimates of heritability for CD traits in the PEN
      and CEN data sets ranged from 0.20 to 0.31, with greater values in the first
      calving opportunity. Genetic correlations were positive and medium to high in
      magnitude, 0.57 to 0.59 in the PEN data set and 0.38 to 0.91 in the CEN data set.
      In the TLMISS data set, heritabilities ranged from 0.19 to 0.23 for CD and 0.37
      to 0.42 for CS. Genetic correlations between CD traits varied between 0.82 and
      0.88; between CS traits, genetic correlations varied between 0.56 and 0.80.
      Negative (genetically favorable), medium to high genetic correlations (-0.54 to 
      0.91) were estimated between CD and CS traits, suggesting that CD could be used
      as an indicator trait for CS. Data recording must improve in quality for
      practical applications in genetic evaluation for fertility traits.

PMID- 17504969
TI  - Endophyte infection level of tall fescue stockpiled for winter grazing does not
      alter the gain of calves nursing lactating beef cows.
AB  - We examined the effect of endophyte infection level of tall fescue (Festuca
      arundinacea Schreb.) used for stockpiled forage on the performance of lactating,
      fallscalving beef cows and their calves. Treatments were endophyte infection
      levels of 20% (low; SEM = 3.5), 51%, (medium; SEM = 1.25), and 89% (high; SEM =
      2.4; 4 replications/treatment). Five cow-calf pairs grazed in each replicate (n =
      60 cow-calf pairs/yr) for 84 d (phase 1) starting on December 2, 2004 (yr 1), and
      December 1, 2005 (yr 2). After 84 d of grazing each treatment, the cattle were
      commingled and fed as a single group (phase 2) until weaning in April of each
      year. Phase 2 allowed measurement of residual effects from grazing stockpiled
      tall fescue with varying levels of endophyte infection. Pregrazing and
      postgrazing forage DM yield, forage nutritive value, and total ergot alkaloid
      concentrations of forage were collected every 21 d during phase 1. Animal
      performance data included cow BW, ADG, and BCS, as well as calf BW and ADG.
      Animal performance was monitored during both phases. Endophyte infection did not
      affect (P = 0.52) apparent intake (pregrazing minus postgrazing forage DM yield)
      of stockpiled tall fescue, because each cow-calf pair consumed 16 +/- 1.7 kg/d
      regardless of treatment. Cow ADG during phase 1 was -0.47 +/-0.43 kg for the low
      treatment, which was greater (P < 0.01) than either the medium (-0.64 +/-0.43 kg)
      or high (-0.74 +/- 0.43 kg) treatments. However, cows that had grazed the high or
      medium treatments in phase 1 lost -0.43 and -0.57 (+/-0.24) kg/d, respectively,
      which was less (P < 0.01) BW loss than the cows in the low (-0.78 +/- 0.24 kg/d)
      treatment during phase 2. By the end of phase 2, cow BW did not differ (528 +/-27
      kg; P = 0.15). Body condition score for cows in the low treatment was greater (P
      = 0.02) than that of the medium and high treatments at the end of phase 1. Body
      condition scores did not change appreciably by the end of phase 2, and
      differences among treatments remained the same as at the end of phase 1 (P =
      0.02). In contrast to cow performance, calf ADG was unaffected (P = 0.10) by
      endophyte level and averaged 0.73 +/- 0.07 kg during phase 1 and 0.44 +/- 0.04 kg
      during phase 2. Our data suggest that fall-calving herds can utilize highly
      infected tall fescue when stockpiled for winter grazing, with little impact on
      cow performance and no impact on calf gain.

PMID- 17504970
TI  - Characterization of biological types of cattle (Cycle VII): influence of
      postpartum interval and estrous cycle length on fertility.
AB  - Genetic improvement in reproductive efficiency through selection is difficult
      because many reproductive traits are binomial and have low heritabilities. Before
      genetic markers can be generated for fertility in cows, greater characterization
      of reproductive phenotypes is needed to understand the components of the trait.
      The current study tested the hypotheses that: 1) breeds vary in postpartum
      interval to estrus (PPIE) and estrous cycle length, 2) a longer estrous cycle
      immediately before breeding increased pregnancy rates, and 3) a greater number of
      cycles before breeding increased conception rates. The postpartum interval to
      estrus, estrous cycle length, and number of cycles before breeding were examined
      in F1 cows (n = 519) obtained from mating Hereford, Angus, and MARC III cows to
      Hereford, Angus, Simmental, Limousin, Charolais, Gelbvieh, and Red Angus sires.
      Cows were classified as having 0, 1, 2, or 3 observed estrous cycles before
      breeding. All traits analyzed were adjusted to constant BCS. Sire breed of the
      cow influenced length of the PPIE and number of cycles before the start of
      breeding (P <0.001). Simmental-sired cows had the shortest PPIE and greatest
      number of cycles before breeding, whereas Limousin-sired cows had the longest
      PPIE and least number of cycles before breeding. Cows with a greater number of
      cycles before breeding did not have greater conception rates than cows that had
      not exhibited standing estrus before breeding (P = 0.87). In cows that cycled
      before breeding, the length of the estrous cycle immediately before breeding was
      influenced by dam breed and BCS (P <0.01). Cows out of Hereford dams had shorter
      estrous cycles than cows out of MARC III or Angus dams, and estrous cycle length
      increased as BCS increased. Conception rate decreased as length of the estrous
      cycle immediately before breeding increased (P = 0.05, -2.2% per d of cycle
      length). Therefore, previously anestrous cows were just as likely to conceive as
      cows that had cycled before breeding, and an increased number of observed estrous
      cycles before breeding did not increase conception rates. There may be an
      influence of the length of estrous cycle immediately before breeding on
      conception rates, possibly because a longer estrous cycle results in a persistent
      follicle with greater potential for a lower quality oocyte. Breed differences in
      PPIE and estrous cycle length suggest that there are genetic components to these
      traits.

PMID- 17504972
TI  - Activation of the orphan endothelial receptor Tie1 modifies Tie2-mediated
      intracellular signaling and cell survival.
AB  - A critical role for Tie1, an orphan endothelial receptor, in blood vessel
      morphogenesis has emerged from mutant mouse studies. Moreover, it was recently
      demonstrated that certain angiopoietin (Ang) family members can activate Tie1. We
      report here that Ang1 induces Tie1 phosphorylation in endothelial cells. Tie1
      phosphorylation was, however, Tie2 dependent because 1) Ang1 failed to induce
      Tie1 phosphorylation when Tie2 was down-regulated in endothelial cells; 2) Tie1
      phosphorylation was induced in the absence of Ang1 by either a constitutively
      active form of Tie2 or a Tie2 agonistic antibody; 3) in HEK 293 cells Ang1
      phosphorylated a form of Tie1 without kinase activity when coexpressed with Tie2,
      and Ang1 failed to phosphorylate Tie1 when coexpressed with kinase-defective
      Tie2. Ang1-mediated AKT and 42/44MAPK phosphorylation is predominantly Tie2
      mediated, and Tie1 down-regulates this pathway. Finally, based on a battery of in
      vitro and in vivo data, we show that a main role for Tie1 is to modulate blood
      vessel morphogenesis by virtue of its ability to down-regulate Tie2-driven
      signaling and endothelial survival. Our new observations help to explain why Tie1
      null embryos have increased capillary densities in several organ systems. The
      experiments also constitute a paradigm for how endothelial integrity is fine
      tuned by the interplay between closely related receptors by a single growth
      factor.

PMID- 17504973
TI  - Mechanical load initiates hypertrophic scar formation through decreased cellular
      apoptosis.
AB  - Hypertrophic scars occur following cutaneous wounding and result in severe
      functional and esthetic defects. The pathophysiology of this process remains
      unknown. Here, we demonstrate for the first time that mechanical stress applied
      to a healing wound is sufficient to produce hypertrophic scars in mice. The
      resulting scars are histopathologically identical to human hypertrophic scars and
      persist for more than six months following a brief (one-week) period of augmented
      mechanical stress during the proliferative phase of wound healing. Resulting
      scars are structurally identical to human hypertrophic scars and showed dramatic
      increases in volume (20-fold) and cellular density (20-fold). The increased
      cellularity is accompanied by a four-fold decrease in cellular apoptosis and
      increased activation of the prosurvival marker Akt. To clarify the importance of
      apoptosis in hypertrophic scar formation, we examine the effects of mechanical
      loading on cutaneous wounds of animals with altered pathways of cellular
      apoptosis. In p53-null mice, with down-regulated cellular apoptosis, we observe
      significantly greater scar hypertrophy and cellular density. Conversely, scar
      hypertrophy and cellular density are significantly reduced in proapoptotic BclII
      null mice. We conclude that mechanical loading early in the proliferative phase
      of wound healing produces hypertrophic scars by inhibiting cellular apoptosis
      through an Akt-dependent mechanism.

PMID- 17504974
TI  - The 5-HT transporter transactivates the PDGFbeta receptor in pulmonary artery
      smooth muscle cells.
AB  - Serotonin (5-HT) stimulates smooth muscle cell growth through 5-HT receptors and
      the 5-HT transporter (5-HTT), and has been associated with pulmonary hypertension
      (PH). Platelet-derived growth factor receptors (PDGFR) have also been associated
      with PH. We present evidence for the first time that 5-HT transactivates
      PDGFRbeta through the 5-HTT in pulmonary artery (PA) SMCs. Inhibition of PDGFR
      kinase with imatinib or AG1296 blocks 5-HT-stimulated PDGFRbeta phosphorylation.
      5-HTT inhibitors and the Na+/K+-ATPase inhibitor ouabain, but not 5-HT2 and 5
      HT1B/1D receptor inhibitors, block PDGFRbeta activation by 5-HT. Notably, 5-HTT
      binds the PDGFRbeta upon 5-HT stimulation and the 5-HTT inhibitor fluoxetine
      blocks both the binding and PDGDRbeta activation. Activation of PDGFRbeta may
      occur through oxidation of a catalytic cysteine of tyrosine phosphatase. 5-HT
      activated PDGFRbeta phosphorylation is blocked by the antioxidant N-acetyl-L
      cysteine and the NADPH oxidase inhibitor, DPI. Inhibition of PDGFR kinase with
      imatinib or AG1296 significantly inhibits SMC proliferation and migration induced
      by 5-HT in vitro. Infusion of 5-HT by miniosmotic pumps enhances PDGFRbeta
      activation in mouse lung in vivo. In summary, these results demonstrate that 5-HT
      transactivates PDGFRbeta in PASMCs leading to SMC proliferation and migration,
      and may be an important signaling pathway in the production of PH in vivo.

PMID- 17504975
TI  - Sequential actions of ERK1/2 on the AP-1 transcription factor allow temporal
      integration of metabolic signals in pancreatic beta cells.
AB  - The AP-1 transcription factor composed of fos and jun gene products mediates
      transcriptional responses to hormonal and metabolic stimulations of pancreatic
      beta cells. Here, we investigated the mechanisms that dynamically control
      expression of AP-1 subunit proteins. In MIN6 cells, glucose and GLP-1 raised c
      FOS protein with biphasic kinetics, an initial peak being followed by a plateau
      that persisted as long as stimuli were maintained. ERK1/2 activation paralleled c
      FOS expression. Whereas initial induction of c-FOS protein required ERK1/2
      dependent activation of c-fos transcription and de novo protein synthesis,
      persistent accumulation of c-FOS under sustained stimulation did not. Indeed,
      dependent on ERK1/2 activation, c-FOS accumulated in its hyperphosphorylated form
      protected from degradation through the proteasome pathway. The implication of
      ERK1/2 in the accumulation of c-FOS protein was confirmed in rat primary beta
      cells, and the functional consequences of this mechanism were demonstrated with
      DNA-binding and reporter assays. Altogether these findings reveal a sequential
      regulation of AP-1 by ERK1/2, which initially increases transcription of c-fos
      and, if stimulation persists, stabilizes freshly synthesized c-FOS protein to
      efficiently activate the transcription of AP-1-regulated genes. This ERK1/2-AP-1
      module can function as a temporal integrator converting metabolic stimuli of
      different durations into differential transcriptional outputs.

PMID- 17504976
TI  - Methylglyoxal induces advanced glycation end product (AGEs) formation and
      dysfunction of PDGF receptor-beta: implications for diabetic atherosclerosis.
AB  - PURPOSE: Low molecular weight carbonyl compounds, such as the alpha-ketoaldehydes
      methylglyoxal (MGO) and glyoxal (GO), are formed under hyperglycemic conditions
      and behave as advanced glycation end product (AGE) precursors. They form adducts
      on proteins, thereby inducing cellular dysfunctions involved in chronic
      complications of diabetes. METHODS AND MAIN FINDINGS: Nontoxic concentrations of
      GO or MGO altered the PDGF-induced PDGFRbeta-phosphorylation, ERK1/2-activation,
      and nuclear translocation, and the subsequent proliferation of mesenchymal cells
      (smooth muscle cells and skin fibroblasts). This resulted mainly from inhibition
      of the intrinsic tyrosine kinase of PDGFRbeta and in part from altered PDGF-BB
      binding to PDGFRbeta. Concomitantly, the formation of AGE adducts
      (N(epsilon)carboxymethyl-lysine and N(epsilon)carboxyethyl-lysine) was observed
      on immunoprecipitated PDGFRbeta. Arginine and aminoguanidine, used as carbonyl
      scavengers, reversed the inhibitory effect and the formation of AGE adducts on
      PDGFRbeta. AGE-PDGFRbeta adducts were also detected by anti-AGE antibodies in
      PDGFRbeta immunopurified from aortas of diabetic (streptozotocin-treated)
      compared to nondiabetic apolipoprotein E-null mice. Mass spectrometry analysis of
      aortas demonstrated increased AGE formation in diabetic specimens. CONCLUSIONS:
      These data indicate that MGO and GO induce desensitization of PDGFRbeta that
      helps to reduce mesenchymal cell proliferation.

PMID- 17504977
TI  - Hypoxia up-regulates the angiogenic cytokine secretoneurin via an HIF-1alpha- and
      basic FGF-dependent pathway in muscle cells.
AB  - Expression of angiogenic cytokines like vascular endothelial growth factor is
      enhanced by hypoxia. We tested the hypothesis that decreased oxygen levels up
      regulate the angiogenic factor secretoneurin. In vivo, muscle cells of mouse
      ischemic hind limbs showed increased secretoneurin expression, and inhibition of
      secretoneurin by a neutralizing antibody impaired the angiogenic response in this
      ischemia model. In a mouse soft tissue model of hypoxia, secretoneurin was
      increased in subcutaneous muscle fibers. In vitro, secretoneurin mRNA and protein
      were up-regulated in L6 myoblast cells after exposure to low oxygen levels. The
      hypoxia-dependent regulation of secretoneurin was tissue specific and was not
      observed in endothelial cells, vascular smooth muscle cells, or AtT20 pituitary
      tumor cells. The hypoxia-dependent induction of secretoneurin in L6 myoblasts is
      regulated by hypoxia-inducible factor-1alpha, since inhibition of this factor
      using si-RNA inhibited up-regulation of secretoneurin. Induction of secretoneurin
      by hypoxia was dependent on basic fibroblast growth factor in vivo and in vitro,
      and inhibition of this regulation by heparinase suggests an involvement of low
      affinity basic fibroblast growth factor binding sites. In summary, our data show
      that the angiogenic cytokine secretoneurin is up-regulated by hypoxia in muscle
      cells by hypoxia-inducible factor-1alpha- and basic fibroblast growth factor
      dependent mechanisms.

PMID- 17504978
TI  - An initiative to support non-industry-sponsored clinical research is needed.

PMID- 17504979
TI  - Vascular endothelial growth factor and its relationship to inflammatory
      mediators.
AB  - Inflammation occurs in response to host injury or infection, as the result of an
      autoimmune disease, or in response to the development of a tumor. Although the
      immune system may be helpful in fighting the tumor, it may also fuel the
      tumorigenic process. In fact, recent data suggest a strong link between chronic
      inflammation, angiogenesis, and the development of cancer. For example,
      inflammation and scarring caused by recurring infections with Mycobacterium
      tuberculosis may be a cause for cancers of the lung. Inflammatory breast cancer
      exhibits increased angiogenesis and lymphangiogenesis and has a higher metastatic
      potential than noninflammatory breast cancer. Nonsteroidal anti-inflammatory
      drugs have been proposed as preventives for the development of colon carcinoma
      and ovarian cancer. Inhibition of nuclear factor-kappaB contributes to the
      proposed mechanism of action. Inflammatory cytokines, including interleukin-6,
      serve as autocrine and paracrine growth factors for several cancers, and high
      levels of these cytokines may correlate with a poor prognosis and increased
      production of angiogenic factors. The state of the art of our understanding of
      this critical interaction is reviewed.

PMID- 17504980
TI  - Standardizing slide-based assays in breast cancer: hormone receptors, HER2, and
      sentinel lymph nodes.
AB  - Despite the rapid expansion of novel diagnostics designed to personalize breast
      cancer care, there remain several significant unmet needs for improving the
      accuracy and reliability of tests that are already in common daily clinical
      practice. For example, although immunohistochemistry has been the predominant
      method for measuring estrogen receptor and progesterone receptor status for over
      15 years, this assay remains unstandardized and there is a widespread concern
      that inaccuracy in immunohistochemistry technique and interpretation is leading
      to an unacceptably high error rate in determining the true hormone receptor
      status. Similarly, there is considerable concern that both false-negative and
      false-positive result rates for testing for HER2 status are unacceptably high in
      current clinical practice. This commentary considers a variety of factors,
      including preanalytic conditions and slide-scoring procedures, and other
      variables that may be contributing to current testing error rates and why there
      is a great need for the standardization of these biomarker assay procedures to
      further enable the highest possible quality of care for newly diagnosed breast
      cancer patients.

PMID- 17504981
TI  - Masquerader: high mobility group box-1 and cancer.
AB  - Since its identification a third of a century ago, the high-mobility group box-1
      (HMGB1) protein has been linked to varied diverse cellular processes, including
      release from necrotic cells and secretion by activated macrophages engulfing
      apoptotic cells. Initially described as solely chromatin-associated, HMGB1 was
      additionally discovered in the cytoplasm of several types of cultured mammalian
      cells 6 years later. In addition to its intracellular role, HMGB1 has been
      identified extracellularly as a putative leaderless cytokine and differentiation
      factor. In the years since its discovery, HMGB1 has also been implicated in
      disease states, including Alzheimer's, sepsis, ischemia-reperfusion, arthritis,
      and cancer. In cancer, overexpression of HMGB1, particularly in conjunction with
      its receptor for advanced glycation end products, has been associated with the
      proliferation and metastasis of many tumor types, including breast, colon,
      melanoma, and others. This review focuses on current knowledge and speculation on
      the role of HMGB1 in the development of cancer, metastasis, and potential targets
      for therapy.

PMID- 17504982
TI  - Microtubule-associated proteins as targets in cancer chemotherapy.
AB  - Natural and synthetic compounds that disrupt microtubule dynamics are among the
      most successful and widely used cancer chemotherapeutic agents. However, lack of
      reliable markers that predict sensitivity of cancers to these agents and
      development of resistance remain vexing issues. There is accumulating evidence
      that a family of cellular proteins that are associated with and alter the
      dynamics of microtubules can determine sensitivity of cancer cells to microtubule
      targeting agents and play a role in tumor cell resistance to these agents. This
      growing family of microtubule-associated proteins (MAP) includes products of
      oncogenes, tumor suppressors, and apoptosis regulators, suggesting that
      alteration of microtubule dynamics may be one of the critical events in
      tumorigenesis and tumor progression. The objective of this review is to integrate
      the knowledge on these seemingly unrelated proteins that share a common function
      and examine their relevance to microtubule-targeting therapies and highlight MAPs
      tubulin-drug interactions as a novel avenue for new drug discovery. Based on the
      available evidence, we propose that rational microtubule-targeting cancer
      therapeutic approaches should ideally include proteomic profiling of tumor MAPs
      before administration of microtubule-stabilizing/destabilizing agents
      preferentially in combination with agents that modulate the expression of
      relevant MAPs.

PMID- 17504983
TI  - Heat shock protein 27 protects L929 cells from cisplatin-induced apoptosis by
      enhancing Akt activation and abating suppression of thioredoxin reductase
      activity.
AB  - PURPOSE: Heat shock protein 27 (Hsp27) is up-regulated in multiple malignancies
      and implicated in cisplatin resistance. It is attempted to know how Hsp27 endues
      cell with cisplatin resistance by interfering with upstream of both apoptosis
      signal-regulating kinase 1 (ASK1)/p38 mitogen-activated protein kinase-activated
      apoptotic signaling and serine/threonine kinase Akt-dependent survival signaling.
      EXPERIMENTAL DESIGN: The mouse L929 cells stably transfected with human Hsp27 or
      its dominant-negative mutant and the human cervical cancer HeLa cells transfected
      with Hsp27 siRNA were used. The cisplatin-induced apoptosis and activation of
      ASK1, p38, and Akt were compared in control cells, cells overexpressing Hsp27,
      and cells with their endogenous Hsp27 knocked down. RESULTS: Hsp27 effectively
      protected the cells from cisplatin-induced DNA fragmentation. The p38 inhibitors
      obviously decreased whereas Akt inhibitors markedly increased the apoptotic
      fraction in cisplatin-treated cells. Overexpression of Hsp27 doubly enhanced the
      drug-induced Akt activation while substantially depressing the drug-induced
      activation of ASK1 and p38. Knockdown of the endogenous Hsp27 in HeLa cells
      resulted in the effects opposite to that observed in the Hsp27-overexpressing
      cells. Enhancement of Akt activation is associated with complex formation between
      Akt and Hsp27, whereas depression of ASK1/p38 activation is attributed to a
      reversion of the drug-induced inhibition of thioredoxin reductase activity and
      subsequent oxidation of thioredoxin. CONCLUSIONS: Hsp27 endues cells with
      cisplatin resistance via depression of the drug-induced ASK1/p38 activation and
      enhancement of the drug-induced Akt activation. This study revealed the
      intervention of Hsp27 in upstream of both ASK1/p38 apoptotic signaling and
      phosphatidylinositol 3-kinase/Akt survival signaling. Therefore, the inhibition
      of Hsp27 may be a novel strategy of cancer chemotherapy.

PMID- 17504984
TI  - Microsatellite instability markers for identifying early-onset colorectal cancers
      caused by germ-line mutations in DNA mismatch repair genes.
AB  - PURPOSE: Microsatellite instability (MSI) testing of colorectal cancer tumors is
      used as a screening tool to identify patients most likely to be mismatch repair
      (MMR) gene mutation carriers. We wanted to examine which microsatellite markers
      currently used to detect MSI best predict early-onset colorectal cancer caused by
      germ-line mutations in MMR genes. EXPERIMENTAL DESIGN: Invasive primary tumors
      from a population-based sample of 107 cases of colorectal cancer diagnosed before
      age 45 years and tested for germ-line mutations in MLH1, MSH2, MSH6, and PMS2 and
      MMR protein expression were screened for MSI using the National Cancer Institute
      panel and an expanded 10-microsatellite marker panel. RESULTS: The National
      Cancer Institute five-marker panel system scored 31 (29%) as (NCI)MSI-High, 13
      (12%) as (NCI)MSI-Low, and 63 (59%) as (NCI)MS-Stable. The 10-marker panel
      classified 18 (17%) as (10)MSI-High, 17 (16%) as (10)MSI-Low, and 72 (67%) as
      (10)MS-Stable. Of the 26 cancers that lacked the expression of at least one MMR
      gene, 24 (92%) were positive for some level of MSI (using either microsatellite
      panel). The mononucleotide repeats Bat26, Bat40, and Myb were unstable in all
      (10)MSI-High cancers and all MLH1 and MSH2 mutation carriers (100% sensitive).
      Bat40 and Bat25 were unstable in all tumors of MSH6 mutation carriers (100%
      sensitive). Bat40 was unstable in all MMR gene mutation carriers (100%
      sensitive). By incorporating seven mononucleotide repeats markers into the 10
      marker panel, we were able to distinguish the carriers of MSH6 mutations (all
      scored (10)MSI-Low) from the MLH1 and MSH2 mutation carriers (all scored (10)MSI
      High). CONCLUSIONS: In early-onset colorectal cancer, a microsatellite panel
      containing a high proportion of mononuclear repeats can distinguish between
      tumors caused by MLH1 and MSH2 mutations from those caused by MSH6 mutations.

PMID- 17504985
TI  - Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer.
AB  - PURPOSE: Hemostatic activation is common in pancreatic cancer and may be linked
      to angiogenesis and venous thromboembolism. We investigated expression of tissue
      factor (TF), the prime initiator of coagulation, in noninvasive and invasive
      pancreatic neoplasia. We correlated TF expression with vascular endothelial
      growth factor (VEGF) expression, microvessel density, and venous thromboembolism
      in resected pancreatic cancer. EXPERIMENTAL DESIGN: Tissue cores from a tri
      institutional retrospective series of patients were used to build tissue
      microarrays. TF expression was graded semiquantitatively using
      immunohistochemistry in normal pancreas (n=10), intraductal papillary mucinous
      neoplasms (n=70), pancreatic intraepithelial neoplasia (n=40), and resected or
      metastatic pancreatic adenocarcinomas (n=130). RESULTS: TF expression was
      observed in a majority of noninvasive and invasive pancreatic neoplasia,
      including 77% of pancreatic intraepithelial neoplasias, 91% of intraductal
      papillary mucinous neoplasms, and 89% of pancreatic cancers, but not in normal
      pancreas. Sixty-six of 122 resected pancreatic cancers (54%) were found to have
      high TF expression (defined as grade >or=2, the median score). Carcinomas with
      high TF expression were more likely to also express VEGF (80% versus 27% with low
      TF expression, P<0.0001) and had a higher median MVD (8 versus 5 per tissue core
      with low TF expression, P=0.01). Pancreatic cancer patients with high TF
      expression had a venous thromboembolism rate of 26.3% compared with 4.5% in
      patients with low TF expression (P=0.04). CONCLUSIONS: TF expression occurs early
      in pancreatic neoplastic transformation and is associated with VEGF expression,
      increased microvessel density, and possibly clinical venous thromboembolism in
      pancreatic cancer. Prospective studies evaluating the role of TF in pancreatic
      cancer outcomes are warranted.

PMID- 17504986
TI  - Prospective assessment of XPD Lys751Gln and XRCC1 Arg399Gln single nucleotide
      polymorphisms in lung cancer.
AB  - PURPOSE: XRCC1 and XPD play key roles in the repair of DNA lesions and adducts.
      Contrasting findings have been reported on the effect of polymorphisms of these
      genes on the response to platinum-based chemotherapy in advanced non-small-cell
      lung cancer (NSCLC). This study aimed to investigate the relationship between the
      XPD Lys751Gln and XRCC1 Arg399Gln genotypes and outcome in lung cancer patients.
      EXPERIMENTAL DESIGN: We genotyped 203 NSCLC and 45 small-cell lung carcinoma
      (SCLC) patients for the two polymorphisms. Most of the patients (81%) received a
      platinum-based chemotherapy. RESULTS: The patients' genotype frequencies did not
      significantly differ from controls and both groups were in Hardy-Weinberg
      equilibrium for the two polymorphisms. The XRCC1399 Gln/Gln variant genotype was
      associated with a higher median survival time (80 weeks versus 54.6 weeks for the
      Arg/Gln heterozygous and 55.6 weeks for the wild-type Arg/Arg genotype; P=0.09).
      At the multivariable analysis adjusted for histology, stage of the disease,
      performance status, age, and gender, the Gln/Gln genotype was associated with a
      better survival of borderline significance in the subgroup of patients treated
      with cisplatin (hazard ratio, 0.55; 95% CI, 0.30-1.00); this association became
      significant for those with grade 3-4 clinical toxicity (hazard ratio, 0.46; 95%
      CI, 0.22-0.98). No association between XPD Lys751Gln genotype and clinical
      outcome was found. CONCLUSION: This prospective investigation provides suggestive
      evidence of a favorable effect of the XRCC1399 Gln/Gln genotype on survival in
      platinum-treated NSCLC and, for the first time, in SCLC patients also. This
      contrasts with other authors who did not include non-platinum-treated patients,
      but it does fit the expectation for a suboptimal ability to remove DNA adducts.

PMID- 17504987
TI  - Differential methylation hybridization array of endometrial cancers reveals two
      novel cancer-specific methylation markers.
AB  - PURPOSE: To identify novel endometrial cancer-specific methylation markers and to
      determine their association with clinicopathologic variables and survival
      outcomes. EXPERIMENTAL DESIGN: Differential methylation hybridization analysis
      (DMH) was done for 20 endometrioid endometrial cancers using normal endometrial
      DNA as a reference control. Combined bisulfite restriction analysis (COBRA) was
      used to verify methylation of sequences identified by DMH. Bisulfite sequencing
      was undertaken to further define CpG island methylation and to confirm the
      reliability of the COBRA. The methylation status of newly identified markers and
      the MLH1 promoter was evaluated by COBRA in a large series of endometrioid
      (n=361) and non-endometrioid uterine cancers (n=23). RESULTS: DMH and COBRA
      identified two CpG islands methylated in tumors but not in normal DNAs: SESN3
      (PY2B4) and TITF1 (SC77F6/154). Bisulfite sequencing showed dense methylation of
      the CpG islands and confirmed the COBRA assays. SESN3 and TITF1 were methylated
      in 20% and 70% of endometrioid tumors, respectively. MLH1 methylation was seen in
      28% of the tumors. TITF1 and SESN3 methylation was highly associated with MLH1
      methylation (P<0.0001). SESN3 and TITF1 were methylated in endometrioid and non
      endometrioid tumors, whereas MLH1 methylation was restricted to endometrioid
      tumors. Methylation at these markers was not associated with survival outcomes.
      CONCLUSIONS: The 5' CpG islands for SESN3 and TITF1 are novel cancer-specific
      methylation markers. Methylation at these loci is strongly associated with
      aberrant MLH1 methylation in endometrial cancers. SESN3, TITF1 and MLH1
      methylation did not predict overall survival or disease-free survival in this
      large cohort of patients with endometrioid endometrial cancer.

PMID- 17504988
TI  - KRAS mutation is an important predictor of resistance to therapy with epidermal
      growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer.
AB  - PURPOSE: EGFR gene mutations and increased EGFR copy number have been associated
      with favorable response to epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors (EGFR-TKI) in patients with non-small-cell lung cancer (NSCLC).
      In contrast, KRAS mutation has been shown to predict poor response to such
      therapy. We tested the utility of combinations of these three markers in
      predicting response and survival in patients with NSCLC treated with EGFR-TKIs.
      EXPERIMENTAL DESIGN: Patients with advanced NSCLC treated with EGFR-TKI with
      available archival tissue specimens were included. EGFR and KRAS mutations were
      analyzed using PCR-based sequencing. EGFR copy number was analyzed using
      fluorescence in situ hybridization. RESULTS: The study included 73 patients, 59
      of whom had all three potential markers successfully analyzed. EGFR mutation was
      detected in 7 of 71 patients (9.8%), increased EGFR copy number in 32 of 59
      (54.2%), and KRAS mutation in 16 of 70 (22.8%). EGFR mutation (P<0.0001) but not
      increased EGFR copy number (P=0.48) correlated with favorable response. No
      survival benefit was detected in patients with either of these features. KRAS
      mutation correlated with progressive disease (P=0.04) and shorter median time to
      progression (P=0.0025) but not with survival. Patients with both EGFR mutation
      and increased EGFR copy number had a >99.7% chance of objective response, whereas
      patients with KRAS mutation with or without increased EGFR copy number had a
      >96.5% chance of disease progression. CONCLUSION: KRAS mutation should be
      included as indicator of resistance in the panel of markers used to predict
      response to EGFR-TKIs in NSCLC.

PMID- 17504989
TI  - Magnetic resonance imaging determination of tumor grade and early response to
      temozolomide in a genetically engineered mouse model of glioma.
AB  - PURPOSE: The median survival for patients diagnosed with glioblastoma multiforme,
      the most common type of brain tumor, is less than 1 year. Animal glioma models
      that are more predictive of therapeutic response in human patients than
      traditional models and that are genetically and histologically accurate are an
      unmet need. The nestin tv-a (Ntv-a) genetically engineered mouse spontaneously
      develops glioma when infected with ALV-A expressing platelet-derived growth
      factor, resulting in autocrine platelet-derived growth factor signaling.
      EXPERIMENTAL DESIGN: In the Ntv-a genetically engineered mouse model, T2-weighted
      and T1-weighted, contrast-enhanced magnetic resonance images were correlated with
      histology, glioma grade (high or low), and survival. Magnetic resonance imaging
      (MRI) was therefore used to enroll mice with high-grade gliomas into a second
      study that tested efficacy of the current standard of care for glioma,
      temozolomide (100 mg/kg qdx5 i.p., n=13). RESULTS: The Ntv-a model generated a
      heterogeneous group of gliomas, some with high-grade growth rate and histologic
      characteristics and others with characteristics of lower-grade gliomas. We showed
      that MRI could be used to predict tumor grade and survival. Temozolomide
      treatment of high-grade tv-a gliomas provided a 14-day growth delay compared with
      vehicle controls. Diffusion MRI measurement of the apparent diffusion coefficient
      showed an early decrease in cellularity with temozolomide, similar to that
      observed in humans. CONCLUSIONS: The use of MRI in the Ntv-a model allows
      determination of glioma grade and survival prediction, distribution of mice with
      specific tumor types into preclinical trials, and efficacy determination both by
      tumor growth and early apparent diffusion coefficient response.

PMID- 17504990
TI  - A 10-gene classifier for distinguishing head and neck squamous cell carcinoma and
      lung squamous cell carcinoma.
AB  - PURPOSE: The risk of developing metastatic squamous cell carcinoma for patients
      with head and neck squamous cell carcinoma (HNSCC) is very high. Because these
      patients are often heavy tobacco users, they are also at risk for developing a
      second primary cancer, with squamous cell carcinoma of the lung (LSCC) being the
      most common. The distinction between a lung metastasis and a primary LSCC is
      currently based on certain clinical and histologic criteria, although the
      accuracy of this approach remains in question. EXPERIMENTAL DESIGN: Gene
      expression patterns derived from 28 patients with HNSCC or LSCC from a single
      center were analyzed using penalized discriminant analysis. Validation was done
      on previously published data for 134 total subjects from four independent
      Affymetrix data sets. RESULTS: We identified a panel of 10 genes (CXCL13, COL6A2,
      SFTPB, KRT14, TSPYL5, TMP3, KLK10, MMP1, GAS1, and MYH2) that accurately
      distinguished these two tumor types. This 10-gene classifier was validated on 122
      subjects derived from four independent data sets and an average accuracy of 96%
      was shown. Gene expression values were validated by quantitative reverse
      transcription-PCR derived on 12 independent samples (seven HNSCC and five LSCC).
      The 10-gene classifier was also used to determine the site of origin of 12 lung
      lesions from patients with prior HNSCC. CONCLUSIONS: The results suggest that
      penalized discriminant analysis using these 10 genes will be highly accurate in
      determining the origin of squamous cell carcinomas in the lungs of patients with
      previous head and neck malignancies.

PMID- 17504991
TI  - The graft content of donor T cells expressing gamma delta TCR+ and CD4+foxp3+
      predicts the risk of acute graft versus host disease after transplantation of
      allogeneic peripheral blood stem cells from unrelated donors.
AB  - PURPOSE: Recently, high numbers of regulatory T cells within the stem cell graft
      were described to be associated with less graft-versus-host disease (GVHD) after
      related peripheral blood stem cell transplantation (PBSCT). Studies in mice also
      suggest a distinct role of gamma delta TCR(+) T cells in mediating GVHD.
      Therefore, the aim of this study was to define the yet-unknown role of regulatory
      and gamma delta TCR(+) T cells in human PBSCT from unrelated donors. EXPERIMENTAL
      DESIGN: The frequency of both T-cell subsets within the graft was analyzed in 63
      patients receiving unrelated allogeneic PBSCT. The respective amounts were
      quantified by flow cytometry and PCR and further correlated with clinical
      outcome. RESULTS: The grafts contained a median of 11.2 x 10(6)/kg CD4(+)foxp3(+)
      and 9.8 x 10(6)/kg gamma delta TCR(+) T cells, respectively. Patients receiving
      more CD4(+)foxp3(+) cells had a lower cumulative incidence of acute GVHD II-IV
      (44% versus 65%, P=0.03). Interestingly, in patients who received higher
      concentrations of donor gamma delta TCR(+) T cells, acute GVHD II-IV was more
      frequent (66% versus 40%, P=0.02). In multivariate analysis, only the graft
      concentration of gamma delta TCR(+) T cells (P=0.002) and a positive
      cytomegalovirus status of the recipient (P = 0.03) were significantly associated
      with the occurrence of acute GVHD II-IV. CONCLUSION: Graft composition of T-cell
      subsets seems to affect the outcome of patients receiving allogeneic PBSCT from
      unrelated donors. Therefore, selective manipulation or add-back of particular
      subsets might be a promising strategy to reduce the incidence of GVHD.

PMID- 17504992
TI  - Loss of heterozygosity of chromosome 3 detected with single nucleotide
      polymorphisms is superior to monosomy 3 for predicting metastasis in uveal
      melanoma.
AB  - PURPOSE: Loss of chromosome 3 is strongly associated with metastasis in uveal
      melanoma and has been proposed as the basis for clinical prognostic testing. It
      is not known whether techniques that identify loss of heterozygosity for
      chromosome 3 predict metastasis more accurately than those that detect only
      numerical loss of chromosome 3 (monosomy 3). EXPERIMENTAL DESIGN: Fifty-three
      uveal melanomas were analyzed by 28 single nucleotide polymorphisms (SNP) across
      chromosome 3. SNP was compared with fluorescence in situ hybridization (FISH) and
      array-based comparative genomic hybridization (aCGH) for metastasis prediction by
      sensitivity, specificity, and Kaplan-Meier survival analysis, using our validated
      gene expression-based classifier as a reference standard. RESULTS: By Kaplan
      Meier analysis, only the gene expression-based classifier (P=0.001) and SNP-based
      detection of loss of heterozygosity for chromosome 3 (P=0.04) were significantly
      associated with metastasis. Sensitivity and specificity were 95.2% and 80.8%,
      respectively, for SNP, 77.8% and 64.7%, respectively, for FISH, and 85.0% and
      72.0%, respectively, for aCGH. Isodisomy 3 was identified by SNP but undetected
      by aCGH and FISH in three tumors. CONCLUSIONS: Prognostic tests based on SNP
      platforms, which detect both chromosomal homologues and their subregions, may be
      superior to techniques that only detect changes in chromosome number. These
      observations could have important implications for efforts to detect genetic
      alterations in cancer genomes with CGH-based approaches.

PMID- 17504993
TI  - Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma
      diagnosis and prognosis assessment.
AB  - PURPOSE: Malignant mesothelioma is a highly aggressive tumor and is often
      diagnosed too late for a curative treatment. We compared diagnostic and
      prognostic values of mesothelin and osteopontin in 172 patients suspected of
      malignant pleural mesothelioma (MPM) and in a control group of 112 asymptomatic
      asbestos-exposed subjects. EXPERIMENTAL DESIGN: Osteopontin and mesothelin were
      assayed with commercial ELISA kits in a series of 43 patients with pleural
      metastases of various carcinomas, 33 patients with benign pleural lesions
      associated with asbestos exposure, 96 patients with MPMs, and 112 asbestos
      exposed healthy subjects. Results were correlated with patient's diagnosis and
      survival. RESULTS: Serum osteopontin level was higher in MPM patients compared
      with healthy asbestos-exposed subjects and had a good capability to distinguish
      between these two populations. However, osteopontin was unable to distinguish
      between MPM and pleural metastatic carcinoma or benign pleural lesions associated
      with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more
      powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM
      but was unable to identify patients with nonepithelioid mesothelioma subtypes.
      Survival analysis identified tumor histologic subtype along with serum
      osteopontin and serum mesothelin as independent prognostic factors in
      mesothelioma patients. CONCLUSIONS: Osteopontin has a lower diagnostic accuracy
      than mesothelin in patients suspected of MPM. Insufficient specificity limits
      osteopontin utility as diagnostic marker. Both molecules have a potential value
      as prognostic markers.

PMID- 17504994
TI  - Spectral fluorescence molecular imaging of lung metastases targeting HER2/neu.
AB  - PURPOSE: Surgical resection of pulmonary metastases is now a clinically accepted
      cancer therapy but its success depends on the accurate localization and removal
      of all tumor foci. To enhance the detection of pulmonary metastases during
      surgery, we developed an i.v. administered optical probe that uses a monoclonal
      antibody, Herceptin (trastuzumab), conjugated to a fluorophore, rhodamine green
      (RhodG), to specifically detect human epidermal growth factor receptor type 2
      (HER2/neu)-expressing pulmonary lesions in an animal model of lung metastases.
      EXPERIMENTAL DESIGN: Pulmonary metastases were induced by i.v. injection of gene
      transfected murine embryonic fibroblasts (3T3) cells in a murine model to produce
      a mixed population of HER2+ and HER2- tumors. To image these tumors, an anti-HER2
      (Herceptin) or a control (HUT) complementarity-determining region-grafted
      antibody was conjugated to RhodG and injected i.v. into mice. Spectral
      fluorescence imaging was done after thoracotomy and images were correlated with
      gross and microscopic pathology to assess sensitivity and specificity. RESULTS:
      HER2+ tumors injected with Herceptin-RhodG were more fluorescent than either HER2
      tumors or HER2+ tumors injected with HUT-RhodG at all time points. The maximal
      fluorescence signal in HER2+ tumors injected with Herceptin-RhodG was observed at
      1 day postinjection. The tumors fluoresced primarily at the rim and not their
      center, reflecting the binding-site barrier that is commonly seen with high
      affinity antibodies. CONCLUSION: A HER2-targeted optical imaging probe shows the
      ability to specifically enhance HER2+ pulmonary metastases but not HER2-
      pulmonary metastases. The high sensitivity and specificity of this probe is
      encouraging for the development of antigen-targeted optical probes to assist in
      the resection of pulmonary metastases.

PMID- 17504995
TI  - Gene expression signature predicts recurrence in lung adenocarcinoma.
AB  - PURPOSE: Improving outcomes for early-stage lung cancer is a major research focus
      at present because a significant proportion of stage I patients develop recurrent
      disease within 5 years of curative-intent lung resection. Within tumor stage
      groups, conventional prognostic indicators currently fail to predict relapse
      accurately. EXPERIMENTAL DESIGN: To identify a gene signature predictive of
      recurrence in primary lung adenocarcinoma, we analyzed gene expression profiles
      in a training set of 48 node-negative tumors (stage I-II), comparing tumors from
      cases who remained disease-free for a minimum of 36 months with those from cases
      whose disease recurred within 18 months of complete resection. RESULTS: Cox
      proportional hazards modeling with leave-one-out cross-validation identified a 54
      gene signature capable of predicting risk of recurrence in two independent
      validation cohorts of 55 adenocarcinomas [log-rank P=0.039; hazard ratio (HR),
      2.2; 95% confidence interval (95% CI), 1.1-4.7] and 40 adenocarcinomas (log-rank
      P=0.044; HR, 3.3; 95% CI, 1.4-7.9). Kaplan-Meier log-rank analysis found that
      predicted poor-outcome groups had significantly shorter survival, and
      furthermore, the signature predicted outcome independently of conventional
      indicators of tumor stage and node stage. In a subset of earliest stage
      adenocarcinomas, generally expected to have good outcome, the signature predicted
      samples with significantly poorer survival. CONCLUSIONS: We describe a 54-gene
      signature that predicts the risk of recurrent disease independently of tumor
      stage and which therefore has potential to refine clinical prognosis for patients
      undergoing resection for primary adenocarcinoma of the lung.

PMID- 17504996
TI  - Cyclooxygenase 2 expression in rectal cancer is of prognostic significance in
      patients receiving preoperative radiotherapy.
AB  - PURPOSE: To determine the effect of cyclooxygenase (COX)-2 expression on clinical
      behavior in irradiated and nonirradiated rectal carcinomas. EXPERIMENTAL DESIGN:
      Tumor samples were collected from 1,231 patients of the Dutch TME trial, in which
      rectal cancer patients were treated with standardized surgery and randomized for
      preoperative short-term (5 x 5 Gy) radiotherapy or no preoperative radiotherapy.
      Tissue microarrays were constructed from primary tumor material, and COX-2
      expression was assessed by immunohistochemistry. Tumor cell apoptosis was
      determined by M30 immunostaining. RESULTS: A high level of COX-2 expression after
      radiotherapy was associated with low levels of tumor cell apoptosis (P=0.001).
      COX-2 expression had no significant effect on patient survival or tumor
      recurrence in nonirradiated tumors. However, in patients receiving preoperative
      radiotherapy, high level of COX-2 expression was associated with higher incidence
      of distant recurrences [P=0.003; hazard ratio (HR), 1.7; 95% confidence interval
      (95% CI), 1.2-2.5] and shorter disease-free survival (P=0.002; HR, 1.8; 95% CI,
      1.2-2.5) and overall survival (P=0.009; HR, 1.5; 95% CI, 1.1-2.0), independent of
      patient age, tumor stage, tumor location, or the presence of tumor cells in the
      circumferential resection margin. CONCLUSIONS: A high level of COX-2 expression
      after preoperative radiotherapy in resection specimens is associated with
      apoptosis resistance, high distant recurrence rates, and a poor prognosis in
      rectal cancer.

PMID- 17504997
TI  - Intradermal CpG-B activates both plasmacytoid and myeloid dendritic cells in the
      sentinel lymph node of melanoma patients.
AB  - PURPOSE: A decrease in the frequency and activation state of dendritic cells in
      the sentinel lymph node (SLN) has been observed in early stages of melanoma
      development. This may hinder the generation of effective antitumor T-cell
      responses and increase the likelihood of metastatic spread. Immunopotentiation of
      the melanoma SLN may therefore be a valuable adjuvant treatment option. One way
      to achieve this is through the use of bacterially derived unmethylated cytosine
      phosphate-guanine (CpG) DNA sequences that bind Toll-like receptor 9 and activate
      plasmacytoid dendritic cells (PDC). CpG-activated PDC, in turn, release IFN alpha
      and may thus boost T-cell and natural killer cell responses as well as activate
      conventional myeloid dendritic cells (MDC). EXPERIMENTAL DESIGN: We studied the
      effects of preoperative local administration of the CpG B-type
      oligodeoxynucleotide (ODN) PF-3512676 (formerly known as CPG 7909) on dendritic
      cell and T-cell subsets in the SLN of 23 stage I to III melanoma patients,
      randomized to receive intradermal injections of either PF-3512676 or saline (NaCl
      0.9%). RESULTS: PF-3512676 administration resulted in bulkier SLN, higher yields
      of isolated SLN leukocytes, and activation of BDCA-2(+)CD123(+) PDC as well as of
      CD1a(+) MDC. In addition, PF-3512676 administration was associated with the
      presence of a newly identified CD11c(hi)CD123(+)CD83(+)TRAIL(+) mature SLN-MDC
      subset, an increased release of a variety of inflammatory cytokines, and lower
      frequencies of CD4(+)CD25(hi)CTLA-4(+)FoxP3(+) regulatory T cells in the SLN.
      CONCLUSIONS: These findings point to the possible utility of the conditioning of
      SLN by PF-3512676 as an adjuvant immunotherapeutic modality for early-stage
      melanoma.

PMID- 17504998
TI  - CYP2C9 and CYP2C19 polymorphic forms are related to increased indisulam exposure
      and higher risk of severe hematologic toxicity.
AB  - PURPOSE: The anticancer agent indisulam is metabolized by the cytochrome P450 of
      enzymes CYP2C9 and CYP2C19. Polymorphisms of these enzymes may affect the
      elimination rate of indisulam. Consequently, variant genotypes may be clinically
      relevant predictors for the risk of developing severe hematologic toxicity. The
      purposes of this study were to evaluate the effect of genetic variants of CYP2C9
      and CYP2C19 on the pharmacokinetics of indisulam and on clinical outcome and to
      assess the need for pharmacogenetically guided dose adaptation. EXPERIMENTAL
      DESIGN: Pharmacogenetic screening of CYP2C polymorphisms was done in 67 patients
      treated with indisulam. Pharmacokinetic data were analyzed with a population
      pharmacokinetic model, in which drug elimination was described by a linear and a
      Michaelis-Menten pathway. The relationships between allelic variants and the
      elimination pharmacokinetic parameters (CL, V(max), K(m)) were tested using
      nonlinear mixed-effects modeling. Polymorphisms causing a high risk of dose
      limiting neutropenia were identified in a simulation study. RESULTS: The
      Michaelis-Menten elimination rate (V(max)) was decreased by 27% (P<0.0001) for
      heterozygous CYP2C9*3 mutants. Heterozygous CYP2C19*2 and CYP2C19*3 mutations
      reduced the linear elimination rate (CL) by 38% (P < 0.0001). The risk of severe
      neutropenia was significantly increased by these mutations and dose reductions of
      50 to 100 mg/m(2) per mutated allele may be required to normalize this risk.
      CONCLUSIONS: CYP2C9*3, CYP2C19*2, and CYP2C19*3 polymorphisms resulted in a
      reduced elimination rate of indisulam. Screening for these CYP2C polymorphisms
      and subsequent pharmacogenetically guided dose adaptation may assist in the
      selection of an optimized initial indisulam dosage.

PMID- 17504999
TI  - Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate
      plus the immunologic adjuvant QS-21.
AB  - PURPOSE: To determine the clinical toxicities and antibody response against sTn
      and tumor cells expressing sTn following immunization of high-risk breast cancer
      patients with clustered sTn-KLH [sTn(c)-KLH] conjugate plus QS-21. EXPERIMENTAL
      DESIGN: Twenty-seven patients with no evidence of disease and with a history of
      either stage IV no evidence of disease, rising tumor markers, stage II (>or=4
      positive axillary nodes), or stage III disease received a total of five
      injections each during weeks 1, 2, 3, 7, and 19. Immunizations consisted of
      sTn(c)-KLH conjugate containing 30, 10, 3, or 1 microg sTn(c) plus 100 microg QS
      21. Induction of IgM and IgG antibodies against synthetic sTn(c) and natural sTn
      on ovine submaxillary mucin were measured before and after therapy. Fluorescence
      activated cell sorting analyses assessed reactivity of antibodies to LSC and MCF
      7 tumor cells. RESULTS: The most common toxicities were transient local skin
      reactions at the injection site and mild flu-like symptoms. All patients
      developed significant IgM and IgG antibody titers against sTn(c). Antibody titers
      against ovine submaxillary mucin were usually of lower titers. IgM reactivity
      with LSC tumor cells was observed in 21 patients and with MCF-7 cells in 13
      patients. There was minimal IgG reactivity with LSC cells. CONCLUSION:
      Immunization with sTn(c)-KLH conjugate plus QS-21 is well tolerated and
      immunogenic in high-risk breast cancer patients. Future trials will incorporate
      sTn(c) as a component of a multiple antigen vaccine.

PMID- 17505000
TI  - Temozolomide as monotherapy is effective in treatment of advanced malignant
      neuroendocrine tumors.
AB  - PURPOSE: A retrospective analysis of the toxicity and efficacy of temozolomide in
      advanced neuroendocrine tumors. EXPERIMENTAL DESIGN: Thirty-six patients with
      advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial
      carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine
      foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200
      mg/m(2)) for 5 days every 4 weeks. Patients had previously received a mean of 2.4
      antitumoral medical regimens. Tumor response was evaluated radiologically
      according to the Response Evaluation Criteria in Solid Tumors every 3 months on
      an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was
      also assessed. The expression of O(6)-methylguanine DNA methyltransferase, an
      enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry
      (n=23) and compared with response to temozolomide. RESULTS: Median overall time
      to progression was 7 months (95% confidence interval, 3-10). Radiologic response
      was seen in 14% of patients and stable disease in 53%. Side effects were mainly
      hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer
      Institute toxicity criteria). Ten patients had tumors with O(6)-methylguanine DNA
      methyltransferase immunoreactivity in <10% of nuclei, whereas four patients
      showed radiologic responses. CONCLUSIONS: Temozolomide as monotherapy had
      acceptable toxicity and antitumoral effects in a small series of patients with
      advanced malignant neuroendocrine tumors and four of these showed radiologic
      responses.

PMID- 17505001
TI  - Circulating tumor cells in perioperative esophageal cancer patients: quantitative
      assay system and potential clinical utility.
AB  - PURPOSE: To establish a quantitative system for evaluating the role of
      circulating tumor cells (CTC) in peripheral blood samples in patients who undergo
      surgery for treatment of esophageal cancer. EXPERIMENTAL DESIGN: One hundred
      fifty-five peripheral blood samples from 53 esophageal cancer patients were
      collected before surgery (B-1), immediately after surgery (B0), and on the 3rd
      day postoperatively (B+3). Eighty-nine samples from 22 benign patients who
      underwent thoracotomy and 30 healthy volunteers were obtained as controls. A real
      time reverse transcription-PCR quantitative analysis system based on
      carcinoembryonic antigen (CEA) mRNA gene expression was designed for detection of
      CTC. RESULTS: This developed system can detect CEA mRNA-positive cells down to 3
      cells per milliliter of peripheral blood. The cells in negative control groups
      were lower than the detection limit. The medians of 188 [95% confidence interval
      (95% CI), 155-498], 1513 (95% CI, 660-7,974) and 707 (95% CI, 737-3,005) CEA mRNA
      positive cells per mL with the CEA-positive rates of 28.3%, 60.4%, and 42.9% in B
      1, B0, and B+3 peripheral blood samples were obtained, respectively. There was
      statistically significant difference between B-1 and B0 (P=0.0001) and between B
      1 and B+3 (P=0.0209). Fifty percent of patients with R>0.4 showed metastasis in 1
      year after surgery, whereas the probability was only 14.3% for patients with
      R<0.4 (where R is CTC ratio of B+3 to B0, P=0.043). CONCLUSIONS: Esophageal
      cancer operation results in tumor cells dissemination and significant increase of
      CTC in peripheral blood, which is related to the developed metastasis. CTC are
      helpful for evaluating micrometastasis and have the potential for predicting
      recurrence in esophageal cancer.

PMID- 17505002
TI  - Epidermal growth factor receptor expression in high-grade osteosarcomas is
      associated with a good clinical outcome.
AB  - PURPOSE: The expression of the epidermal growth factor receptor (EGFR) in
      osteosarcomas has repeatedly been described. With the introduction of anti-EGFR
      targeted therapies in clinical practice, these findings regain increased
      attention. Experience with anti-EGFR-targeted therapies in other cancers has made
      clear that besides the expression status of EGFR, a detailed knowledge about gene
      mutations is of major predictive power. We therefore aimed to explore the EGFR
      expression and gene mutation status in high-grade osteosarcomas. EXPERIMENTAL
      DESIGN: We investigated tumor samples of osteosarcoma patients of all age groups
      by means of immunohistochemistry (n=111) and egfr fluorescence in situ
      hybridization (n=39). Sixty-three patients were treated according to the
      Cooperative Osteosarcoma Study Group protocols and complete clinical follow-up
      was available in these cases. RESULTS: Ninety-one of 111 (81%) of osteosarcomas
      revealed an expression of EGFR. EGFR expression showed a dose-response relation
      with improved event-free and overall survival. This was independent of the degree
      of tumor regression due to neoadjuvant chemotherapy. Nine of 39 (23%)
      osteosarcomas showed egfr amplifications by means of fluorescence in situ
      hybridization. All these cases expressed EGFR. When comparing EGFR expression
      between primary biopsy and resection specimen (n=19), viable residual tumor cells
      in resection specimens revealed a lower EGFR expression and a tendency toward
      membranous staining compared with the initial biopsy. CONCLUSIONS: In conclusion,
      expression and amplification of EGFR are frequently observed in high-grade
      osteosarcomas and are associated with improved prognosis in a dose-responsive
      way. This implies that low EGFR expression possibly predicts lack of response to
      conventional treatment in high-grade osteosarcomas and may warrant a more
      intensive therapeutic approach, although not based on EGFR targeting.

PMID- 17505003
TI  - Phase I clinical and pharmacodynamic evaluation of oral CI-1033 in patients with
      refractory cancer.
AB  - PURPOSE: To determine the tolerability and pharmacokinetics of CI-1033 given
      daily for 7 days of a 21-day cycle. Tumor response and changes in erbB receptor
      tyrosine kinase activity in tumor and skin tissue were examined, and modulation
      of potential biomarkers in plasma was explored. DESIGN: This was a dose-finding
      phase I study in patients with advanced solid malignancies. Patients were
      evaluated for safety, pharmacokinetics, and tumor response. Pharmacodynamic
      markers, such as Ki67, p27, and erbB receptor status, were assessed in tumor and
      skin tissue using immunohistochemical and immunoprecipitation methodologies.
      Plasma biomarkers HER2, vascular endothelial growth factor, interleukin-8, and
      matrix metalloproteinase-9 were evaluated using immunologic techniques. RESULTS:
      Fifty-three patients were enrolled in the study. Dose-limiting toxicity (emesis,
      persistent rash, and mouth ulcer) was observed at 750 mg. The maximum tolerated
      dose was 650 mg. There were no confirmed objective responses. CI-1033 treatment
      showed down-regulation of epidermal growth factor receptor, HER2, and Ki67 in a
      variety of tumor tissues and up regulation of p27 in skin tissue. Plasma HER2 was
      reduced following CI-1033 administration, but no consistent change in vascular
      endothelial growth factor, interleukin-8, or matrix metalloproteinase-9 was
      noted. CI-1033 plasma concentrations were proportional to dose. CONCLUSION: The
      safety and pharmacokinetic profile of CI-1033 was favorable for multidose oral
      administration. Evidence of modulation of erbB receptor activity in tumor and
      skin tissue was accompanied by changes in markers of proliferation and cell cycle
      inhibition. Additional clinical trials are warranted in defining the role of CI
      1033 in the treatment of cancer and further assessing the utility of antitumor
      markers.

PMID- 17505004
TI  - Enhancement of docetaxel-induced cytotoxicity by blocking epidermal growth factor
      receptor and cyclooxygenase-2 pathways in squamous cell carcinoma of the head and
      neck.
AB  - PURPOSE: The addition of molecular targeted agents to enhance the cytotoxicity of
      chemotherapeutic agents is a promising strategy in cancer treatment. The
      combination of cyclooxygenase-2 inhibitors and epidermal growth factor receptor
      tyrosine kinase inhibitors, such as celecoxib and ZD1839 (gefitinib), was
      reported to achieve synergistic cell growth inhibition in squamous cell carcinoma
      of the head and neck. Therefore, we postulated that the addition of celecoxib and
      ZD1839 to docetaxel, a cytotoxic agent, might further increase antitumor
      activity. EXPERIMENTAL DESIGN: The combination of celecoxib, ZD1839, and
      docetaxel was studied for its effect on cell growth and apoptosis by cell growth
      inhibition and Annexin V assays. The relevant molecular targets of these agents
      and apoptotic markers were examined by immunoblotting analyses in the presence or
      absence of these three drugs. Morphologic changes of the microtubule
      cytoskeleton, a known target of docetaxel, were also evaluated by staining for
      alpha-tubulin after the combination treatment. RESULTS: We showed that this
      triple combination significantly enhanced cell growth inhibition and docetaxel
      induced apoptosis. Docetaxel mainly induced caspase-8 activation, whereas the
      addition of celecoxib and ZD1839 augmented the caspase-8 activation and enhanced
      caspase-9 activation. One of the underlying mechanisms for augmentation of
      docetaxel-induced apoptosis by celecoxib and ZD1839 is to further inhibit the
      activation of prosurvival pathway molecules, such as extracellular signal
      regulated kinase and AKT, and the promotion of aberrant apoptosis. CONCLUSIONS:
      Our studies suggest that the combination of docetaxel with a cyclooxygenase-2
      inhibitor and an epidermal growth factor receptor tyrosine kinase inhibitor may
      further improve efficacy of docetaxel and other taxane-based therapies in
      squamous cell carcinoma of the head and neck.

PMID- 17505006
TI  - Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor
      growth delay in irradiated lung cancer models.
AB  - PURPOSE: Poly(ADP-ribose) polymerase-1 (PARP-1) is the founding member of a
      family of enzymes that catalyze the addition of ADP-ribose units to proteins that
      mediate DNA repair pathways. Ionizing radiation induces DNA strand breaks,
      suggesting that PARP-1 inhibition may sensitize tumor cells to radiation.
      EXPERIMENTAL DESIGN: We investigated the combination of PARP-1 inhibition with
      radiation in lung cancer models. ABT-888, a novel potent PARP-1 inhibitor, was
      used to explore the effects of PARP-1 inhibition on irradiated tumors and tumor
      vasculature. RESULTS: ABT-888 reduced clonogenic survival in H460 lung cancer
      cells, and inhibited DNA repair as shown by enhanced expression of DNA strand
      break marker histone gamma-H2AX. Both apoptosis and autophagy contributed to the
      mechanism of increased cell death. Additionally, ABT-888 increased tumor growth
      delay at well-tolerated doses in murine models. For a 5-fold increase in tumor
      volume, tumor growth delay was 1 day for ABT-888 alone, 7 days for radiation
      alone, and 13.5 days for combination treatment. Immunohistochemical staining of
      tumor sections revealed an increase in terminal deoxyribonucleotide transferase
      mediated nick-end labeling apoptotic staining, and a decrease in Ki-67
      proliferative staining after combination treatment. Matrigel assay showed a
      decrease in in vitro endothelial tubule formation with ABT-888/radiation
      combination treatment, and von Willebrand factor staining of tumor sections
      revealed decreased vessel formation in vivo, suggesting that this strategy may
      also target tumor angiogenesis. CONCLUSIONS: We conclude that PARP-1 inhibition
      shows promise as an effective means of enhancing tumor sensitivity to radiation,
      and future clinical studies are needed to determine the potential of ABT-888 as a
      radiation enhancer.

PMID- 17505005
TI  - Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3
      activation.
AB  - PURPOSE: Capsaicin, a constituent of green and red peppers, has been linked with
      suppression of tumorigenesis through a mechanism that is not well understood.
      Because the transcription factor signal transducer and activator of transcription
      3 (STAT3) has been closely linked with tumorigenesis, we investigated the effect
      of this vanilloid on the STAT3 pathway in human multiple myeloma cells.
      EXPERIMENTAL DESIGN: The effect of capsaicin on both constitutive and interleukin
      6-induced STAT3 activation, associated protein kinases, and STAT3-regulated gene
      products involved in proliferation, survival and angiogenesis, cellular
      proliferation, and apoptosis in multiple myeloma cells was investigated. RESULTS:
      We found that capsaicin inhibited constitutive activation of STAT3 in multiple
      myeloma cells in a dose- and time-dependent manner, with minimum effect on STAT5.
      Capsaicin also inhibited the interleukin-6-induced STAT3 activation. The
      activation of Janus-activated kinase 1 and c-Src, implicated in STAT3 activation,
      was also inhibited by the vanilloid, with no effect on extracellular signal
      regulated kinase 1/2 activation. Pervanadate reversed the capsaicin-induced down
      regulation of STAT3, suggesting the involvement of a protein tyrosine
      phosphatase. Capsaicin down-regulated the expression of the STAT3-regulated gene
      products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, and vascular endothelial
      growth factor. Finally, capsaicin induced the accumulation of cells in G(1)
      phase, inhibited proliferation, and induced apoptosis, as indicated by caspase
      activation. Capsaicin also significantly potentiated the apoptotic effects of
      Velcade and thalidomide in multiple myeloma cells. When administered i.p.,
      capsaicin inhibited the growth of human multiple myeloma xenograft tumors in male
      athymic nu/nu mice. CONCLUSION: Overall, these results suggest that capsaicin is
      a novel blocker of the STAT3 activation pathway, with a potential role in the
      prevention and treatment of multiple myeloma and other cancers.

PMID- 17505007
TI  - E1A, E1B double-restricted adenovirus with RGD-fiber modification exhibits
      enhanced oncolysis for CAR-deficient biliary cancers.
AB  - PURPOSE: Cancers of biliary system represent highly malignant diseases of dismal
      prognosis. We have previously introduced AxdAdB3, an E1A, E1B double-restricted
      oncolytic adenovirus, which showed excellent oncolytic efficacy for approximately
      half of the biliary cancer lines with an enhanced safety to normal cells. The
      purpose of this study was to evaluate whether RGD-fiber modification (AxdAdB3
      F/RGD), which enables integrin-dependent infection, can improve the infectivity
      and efficacy of AxdAdB3 for biliary cancers. EXPERIMENTAL DESIGN: Expressions of
      adenoviral receptors, coxsackievirus adenovirus receptor (CAR) and integrins
      (alpha(v)beta(3) and alpha(v)beta(5)), were compared with the level of
      infectivity of LacZ-expressing replication-defective adenoviruses with wild-type
      fibers or RGD-modified fibers in a panel of biliary cancer cell lines in vitro.
      Viral replication and cytotoxicity in vitro of AxdAdB3-F/RGD, a novel E1A, E1B
      double-restricted replication-selective adenovirus with RGD-modified fibers, were
      compared with those of its parent virus, AxdAdB3, in various biliary cancer cells
      and in normal cells. In vivo antitumor effects of these oncolytic viruses were
      compared in a xenograft tumor model. RESULTS: Expression of CAR significantly
      correlated with the adenovirus infectivity, whereas integrin alpha(v)beta(5) was
      abundantly expressed in almost all biliary cancer cells. Whereas AxdAdB3
      effectively replicated and lysed only the biliary cancer cells with a preserved
      expression of CAR, AxdAdB3-F/RGD exhibited efficient replication and potent
      oncolysis in both CAR-positive and CAR-negative biliary cancer cells. AxdAdB3
      F/RGD showed attenuated replication and little cytopathy in human normal cells
      (i.e., hepatocytes, WI-38 cells) as well as AxdAdB3. Furthermore, in nude mice
      with s.c. xenografts of CAR-deficient human biliary cancer, i.t. AxdAdB3-F/RGD
      therapy caused a marked inhibition of tumor growth. CONCLUSIONS: The RGD-fiber
      modification strategy enhanced the infectivity, replication, and oncolytic
      effects of the E1A, E1B double-restricted oncolytic adenovirus for CAR-deficient
      biliary cancers. In addition, it preserved the merit of excellent safety of the
      double-restricted virus for normal cells. These results suggest a potential use
      of this agent for the treatment of biliary cancers.

PMID- 17505008
TI  - AZD2171 shows potent antitumor activity against gastric cancer over-expressing
      fibroblast growth factor receptor 2/keratinocyte growth factor receptor.
AB  - PURPOSE: AZD2171 is an oral, highly potent, and selective vascular endothelial
      growth factor signaling inhibitor that inhibits all vascular endothelial growth
      factor receptor tyrosine kinases. The purpose of this study was to investigate
      the activity of AZD2171 in gastric cancer. EXPERIMENTAL DESIGN: We examined the
      antitumor effect of AZD2171 on the eight gastric cancer cell lines in vitro and
      in vivo. RESULTS: AZD2171 directly inhibited the growth of two gastric cancer
      cell lines (KATO-III and OCUM2M), with an IC(50) of 0.15 and 0.37 micromol/L,
      respectively, more potently than the epidermal growth factor receptor tyrosine
      kinase inhibitor gefitinib. Reverse transcription-PCR experiments and
      immunoblotting revealed that sensitive cell lines dominantly expressed COOH
      terminus-truncated fibroblast growth factor receptor 2 (FGFR2) splicing variants
      that were constitutively phosphorylated and spontaneously dimerized. AZD2171
      completely inhibited the phosphorylation of FGFR2 and downstream signaling
      proteins (FRS2, AKT, and mitogen-activated protein kinase) in sensitive cell
      lines at a 10-fold lower concentration (0.1 micromol/L) than in the other cell
      lines. An in vitro kinase assay showed that AZD2171 inhibited kinase activity of
      immunoprecipitated FGFR2 with submicromolar K(i) values ( approximately 0.05
      micromol/L). Finally, we assessed the antitumor activity of AZD2171 in human
      gastric tumor xenograft models in mice. Oral administration of AZD2171 (1.5 or 6
      mg/kg/d) significantly and dose-dependently inhibited tumor growth in mice
      bearing KATO-III and OCUM2M tumor xenografts. CONCLUSIONS: AZD2171 exerted potent
      antitumor activity against gastric cancer xenografts overexpressing FGFR2. The
      results of these preclinical studies indicate that AZD2171 may provide clinical
      benefit in patients with certain types of gastric cancer.

PMID- 17505009
TI  - Increasing anticarcinoma activity of an anti-erbB2 recombinant immunotoxin by the
      addition of an anti-EpCAM sFv.
AB  - PURPOSE: erbB2, the product of the Her2-neu gene, is a well-established
      therapeutic target for antibody-based biologicals, but anti-erbB2 antibody-toxin
      fusion proteins are limited in their activity. The goal of this study was to
      determine if genetically adding an sFv targeting epithelial cell adhesion
      molecule (EpCAM) to an anti-Her2 sFv immunotoxin would result in enhanced
      antitumor activity. EXPERIMENTAL DESIGN: In vitro studies were done in which the
      new bispecific immunotoxin DTEpCAM23 was compared with monospecific immunotoxins
      (DTEpCAM and DT23) to quantitate immunotoxin activity. Mixtures of monospecific
      immunotoxins were tested to determine if they were as effective as the bispecific
      immunotoxin. Binding and internalization studies were also done. In vivo,
      bispecific immunotoxins were given i.t. to athymic nude mice bearing HT-29 human
      colon cancer flank tumors and i.p. to mice with i.p. tumors. RESULTS: DTEpCAM23
      bispecific immunotoxins showed far greater activity than monospecific immunotoxin
      (sometimes over 2,000-fold) against most tumor lines. Bispecific immunotoxin was
      superior and selective in its activity against different carcinoma cell lines.
      Bispecific immunotoxin had greater activity than monospecific immunotoxin
      indicating an advantage of having both sFv on the same single-chain molecule.
      Binding and internalization studies did not explain the differences between
      bispecific immunotoxin and monospecific immunotoxin activity. Orientation of the
      sFvs on the molecule had a significant effect on in vitro and in vivo properties.
      The bispecific immunotoxins were more effective than the monospecific immunotoxin
      in the flank tumor mouse model. CONCLUSIONS: The synthesis of bispecific
      immunotoxin created a new biological agent with superior in vitro and in vivo
      activity (over monospecific immunotoxin), more broad reactivity, more efficacy
      against tumors in vivo, and diminished toxic effects in mice.

PMID- 17505010
TI  - Disruption of endothelial cell interactions with the novel HU177 cryptic collagen
      epitope inhibits angiogenesis.
AB  - PURPOSE: The importance of cellular communication with the extracellular matrix
      in regulating cellular invasion is well established. Selective disruption of
      communication links between cells and the local microenvironment by specifically
      targeting non-cellular matrix-immobilized cryptic extracellular matrix epitopes
      may represent an effective new clinical approach to limit tumor-associated
      angiogenesis. Therefore, we sought to determine whether the HU177 cryptic
      collagen epitope plays a functional role in regulating angiogenesis in vivo.
      EXPERIMENTAL DESIGN: We examined the expression and characterized the HU177
      cryptic collagen epitope in vitro and in vivo using immunohistochemistry and
      ELISA. We examined potential mechanisms by which this cryptic collagen epitope
      may regulate angiogenesis using in vitro cell adhesion, migration, proliferation,
      and biochemical assays. Finally, we examined the whether blocking cellular
      interactions with the HU177 cryptic epitope plays a role in angiogenesis and
      tumor growth in vivo using the chick embryo model. RESULTS: The HU177 cryptic
      epitope was selectively exposed within tumor blood vessel extracellular matrix,
      whereas little was associated with quiescent vessels. An antibody directed to
      this cryptic site selectively inhibited endothelial cell adhesion, migration, and
      proliferation on denatured collagen type IV and induced increased levels of
      cyclin-dependent kinase inhibitor p27(KIP1). Systemic administration of mAb HU177
      inhibited cytokine- and tumor-induced angiogenesis in vivo. CONCLUSIONS: We
      provide evidence for a new functional cryptic regulatory element within collagen
      IV that regulates tumor angiogenesis. These findings suggest a novel and highly
      selective approach for regulating angiogenesis by targeting a non-cellular
      cryptic collagen epitope.

PMID- 17505011
TI  - Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB
      organized lipid complex.
AB  - PURPOSE: Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is a cytotoxic
      retinoid that suffers from a wide interpatient variation in bioavailability when
      delivered orally in a corn oil capsule. The poor bioavailability of the capsule
      formulation may have limited responses in clinical trials, and the large capsules
      are not suitable for young children. To support the hypothesis that a novel
      organized lipid matrix, LYM-X-SORB, can increase the oral bioavailability of
      fenretinide, fenretinide in LYM-X-SORB matrix and in a powderized LYM-X-SORB
      formulation was delivered to mice. EXPERIMENTAL DESIGN: Fenretinide was delivered
      orally to mice as the contents of the corn oil capsule, in LYM-X-SORB matrix (4
      HPR/LYM-X-SORB matrix) or in a LYM-X-SORB matrix powderized with sugar and flour
      (4-HPR/LYM-X-SORB oral powder). Levels of 4-HPR, and its principal metabolite, N
      (4-methoxyphenyl)retinamide, were assayed in plasma and tissues. RESULTS: In a
      dose-responsive manner, from 120 to 360 mg/kg/d, delivery to mice of 4-HPR in LYM
      X-SORB matrix, or as 4-HPR/LYM-X-SORB oral powder, increased 4-HPR plasma levels
      up to 4-fold (P<0.01) and increased tissue levels up to 7-fold (P<0.01) compared
      with similar doses of 4-HPR delivered using capsule contents. Metabolite [N-(4
      methoxyphenyl)retinamide] levels mirrored 4-HPR levels. Two human neuroblastoma
      murine xenograft models showed increased survival (P<0.03), when treated with 4
      HPR/LYM-X-SORB oral powder, confirming the bioactivity of the formulation.
      CONCLUSIONS: 4-HPR/LYM-X-SORB oral powder is a novel, oral drug delivery
      formulation, suitable for pediatric use, which warrants further development for
      the delivery of fenretinide in the treatment of cancer. A phase I clinical trial
      in pediatric neuroblastoma is in progress.

PMID- 17505012
TI  - Tumor-specific efficacy of transforming growth factor-beta RI inhibition in Eker
      rats.
AB  - PURPOSE: Transforming growth factor beta (TGF-beta), which generally stimulates
      the growth of mesenchymally derived cells but inhibits the growth of epithelial
      cells, has been proposed as a possible target for cancer therapy. However,
      concerns have been raised that whereas inhibition of TGF-beta signaling could be
      efficacious for lesions in which TGF-beta promotes tumor development and/or
      progression, systemic pharmacologic blockade of this signaling pathway could also
      promote the growth of epithelial lesions. EXPERIMENTAL DESIGN: We examined the
      effect of a TGF-beta inhibitor on mesenchymal (leiomyoma) and epithelial (renal
      cell carcinoma) tumors in Eker rats, which are genetically predisposed to develop
      these tumors with a high frequency. RESULTS: Blockade of TGF-beta signaling with
      the ALK5/type I TGF-beta R kinase inhibitor, SB-525334, was efficacious for
      uterine leiomyoma; significantly decreasing tumor incidence and multiplicity, and
      reducing the size of these mesenchymal tumors. However, SB-525334 was also
      mitogenic and antiapoptotic for epithelial cells in the kidney and exacerbated
      the growth of epithelial lesions present in the kidneys of these animals.
      CONCLUSION: Although pharmacologic inhibition of TGF-beta signaling with SB
      525334 may be efficacious for mesenchymal tumors, inhibition of this signaling
      pathway seems to promote the development of epithelial tumors.

PMID- 17505013
TI  - Aurora-A and p16 polymorphisms contribute to an earlier age at diagnosis of
      pancreatic cancer in Caucasians.
AB  - PURPOSE: Aurora-A and p16 play a major role in cell cycle checkpoint regulation.
      Both of them are important in the maintenance of centrosome duplication.
      Therefore, we hypothesized that polymorphisms in the two genes may interact or
      work together to influence the finely tuned mechanisms of cell cycle regulation
      that these proteins regulate. The purpose of this study was to investigate the
      association of the Aurora-A (T91A), and p16 (C540G and C580T) polymorphisms with
      age at diagnosis of pancreatic cancer. EXPERIMENTAL DESIGN: We genotyped 148
      Caucasian patients with a diagnosis of pancreatic cancer for the Aurora-A and p16
      polymorphisms using pyrosequencing. We tested the association between age at
      diagnosis and the Aurora-A and p16 genotypes by comparing Kaplan-Meier curves,
      evaluating the homogeneity of the curves using the log-rank test. We used Cox
      proportional hazard regression analysis to estimate the association between time
      to diagnosis and genotype, adjusting for gender. RESULTS: Patients with the
      Aurora-A polymorphic genotypes had a median age at diagnosis with pancreatic
      cancer that was 2.8 years earlier than those with the wild-type genotype [log
      rank, P=0.015; hazard ratio (HR), 1.55; 95% confidence intervals (95% CI), 1.09
      2.20]. There was no significant association between the p16 genotypes and age at
      diagnosis. However, the Aurora-A and p16 C580T polymorphisms combined had a
      synergistic effect on age-associated risk for early diagnosis of pancreatic
      cancer. Compared with patients with wild-type genotypes for both genes, the
      median age at diagnosis for patients with one or two polymorphic alleles for both
      genes was 12.6 years earlier (log-rank, P=0.0002; HR, 3.88; 95% CI, 1.94-7.76).
      No significant associations between the polymorphisms and the cancer metastatic
      status or survival after diagnosis were found. CONCLUSIONS: Our findings suggest
      that the Aurora-A polymorphism contributes to a significantly earlier age at
      diagnosis of pancreatic cancer, and that Aurora-A and p16 C580T polymorphisms
      synergistically contribute to an earlier age at diagnosis of pancreatic cancer.

PMID- 17505014
TI  - Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T
      lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic
      leukemia.
AB  - To determine whether the leukemia-associated Wilms tumor antigen (WT1)
      contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell
      transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T
      cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL
      patients during the early phase of immune recovery after SCT (days 30-120). Seven
      of 10 patients had detectable WT1 expression in their peripheral blood (PB)
      before SCT by quantitative reverse-transcription polymerase chain reaction. Using
      WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining,
      WT1(+) CD8(+) T-cell responses after SCT were found only in patients with
      detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05). To monitor the
      kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT,
      absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each
      time point. The emergence of WT1(+) CD8(+) T cells was associated with a decrease
      in WT1 expression, suggesting a WT1-driven GVL effect. Loss of WT1(+) CD8(+) T
      cell responses was associated with reappearance of WT1 transcripts, consistent
      with a molecular relapse (P < .001). WT1(+) CD8(+) T cells had a predominantly
      effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma. Our
      results support the immunogenicity of WT1 after SCT for ALL and highlight the
      potential for WT1 vaccines to boost GVL after SCT for ALL.

PMID- 17505015
TI  - Gata1 regulates dendritic-cell development and survival.
AB  - Dendritic cells are key initiators and regulators of the immune response.
      Dendritic cell commitment and function require orchestrated regulation of
      transcription. Gata1 is a transcription factor expressed in several hematopoietic
      lineages. However, Gata1 function has not been explored in the monocytic or
      dendritic cell compartment. Here, we show that Gata1 is expressed in myeloid and
      plasmacytoid dendritic cells and that Gata1 ablation affects the survival of
      dendritic cells. Furthermore, lipopolysaccharide (LPS) stimulation of dendritic
      cells prompts Gata1 up-regulation, which is accompanied by increased levels of
      BclX and Ifng. Our findings show that Gata1 is a transcriptional regulator of
      dendritic cell differentiation and suggest that Gata1 is involved in the
      dendritic cell and macrophage lineage separation.

PMID- 17505016
TI  - JAM-A mediates neutrophil transmigration in a stimulus-specific manner in vivo:
      evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration.
AB  - Junctional adhesion molecule-A (JAM-A) is a transmembrane protein expressed at
      tight junctions of endothelial and epithelial cells and on the surface of
      platelets and leukocytes. The role of JAM-A in leukocyte transmigration in vivo
      was directly investigated by intravital microscopy using both a JAM-A
      neutralizing monoclonal antibody (mAb) (BV-11) and JAM-A-deficient (knockout
      [KO]) mice. Leukocyte transmigration (but not adhesion) through mouse cremasteric
      venules as stimulated by interleukin 1beta (IL-1beta) or ischemia/reperfusion
      (I/R) injury was significantly reduced in wild-type mice treated with BV-11 and
      in JAM-A KO animals. In contrast, JAM-A blockade/genetic deletion had no effect
      on responses elicited by leukotriene B(4) (LTB(4)) or platelet-activating factor
      (PAF). Furthermore, using a leukocyte transfer method and mice deficient in
      endothelial-cell JAM-A, evidence was obtained for the involvement of endothelial
      cell JAM-A in leukocyte transmigration mediated by IL-1beta. Investigation of the
      functional relationship between JAM-A and PECAM-1 (CD31) determined that dual
      blockade/deletion of these proteins does not lead to an inhibitory effect greater
      than that seen with blockade/deletion of either molecule alone. The latter
      appeared to be due to the fact that JAM-A and PECAM-1 can act sequentially to
      mediate leukocyte migration through venular walls in vivo.

PMID- 17505017
TI  - Neutrophil interaction with the hemostatic system contributes to liver injury in
      rats cotreated with lipopolysaccharide and ranitidine.
AB  - Cotreatment of rats with nontoxic doses of ranitidine (RAN) and
      lipopolysaccharide (LPS) causes liver injury, and this drug-inflammation
      interaction might be a model for idiosyncratic adverse drug responses in humans.
      Both polymorphonuclear neutrophils (PMNs) and the hemostatic system have been
      shown to be important in the injury. We tested the hypothesis that PMNs cause
      liver injury by interacting with the hemostatic system and producing subsequent
      hypoxia. In rats cotreated with LPS/RAN, PMN depletion by anti-PMN serum reduced
      fibrin deposition and hypoxia in the liver. PMN depletion also reduced the plasma
      concentration of active plasminogen activator inhibitor-1 (PAI-1), a major down
      regulator of the fibrinolytic system. This suggests that PMNs promote fibrin
      deposition by increasing PAI-1 concentration. PMNs were activated in the livers
      of LPS/RAN-cotreated rats as evidenced by increased staining for hypochlorous
      acid-modified proteins generated by the myeloperoxidase-hydrogen peroxide
      chloride system of activated phagocytes. Antiserum against the PMN adhesion
      molecule CD18 protected against LPS/RAN-induced liver injury. Because CD18 is
      important for PMN transmigration and activation, these results suggest that PMN
      activation is required for the liver injury. Furthermore, anti-CD18 serum reduced
      biomarkers of hemostasis and hypoxia, suggesting the necessity for PMN activation
      in the interaction between PMNs and the hemostatic system/hypoxia. Liver injury,
      liver fibrin, and plasma PAI-1 concentration were also reduced by eglin C, an
      inhibitor of proteases released by activated PMNs. In summary, PMNs are activated
      in LPS/RAN-cotreated rats and participate in the liver injury in part by
      contributing to hemostasis and hypoxia.

PMID- 17505018
TI  - Noradrenergic mechanisms in cocaine-induced reinstatement of drug seeking in
      squirrel monkeys.
AB  - Norepinephrine (NE) uptake and NE receptor mechanisms play important modulating
      roles in the discriminative stimulus and stimulant effects of cocaine. The
      present study investigated the role of NE mechanisms in cocaine priming-induced
      reinstatement of extinguished drug seeking. Squirrel monkeys (Saimiri sciureus)
      were trained to stability under a second-order fixed interval, fixed ratio
      schedule of drug self-administration in which operant responding was maintained
      jointly by i.v. cocaine injections and presentations of a cocaine-paired
      stimulus. Drug seeking was then extinguished by replacing cocaine with vehicle
      and eliminating the cocaine-paired stimulus. In test sessions during which the
      cocaine-paired stimulus was reintroduced but only vehicle was available for self
      administration, priming with cocaine, the dopamine transport inhibitor 1-[2-[bis
      (4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909), and the
      NE transport inhibitors nisoxetine and talsupram induced dose-dependent
      reinstatement of drug seeking. The maximum effect of the NE transport inhibitors
      was less than half that of cocaine. Both nisoxetine and talsupram augmented the
      priming effects of a low but not a high dose of cocaine. The priming effects of
      nisoxetine were blocked by the alpha1-adrenoceptor antagonist prazosin, the
      alpha2-adrenoceptor agonist clonidine, and the beta-adrenoceptor antagonist
      propranolol, but not by the dopamine receptor antagonist flupenthixol. The
      priming effects of cocaine were antagonized by clonidine and flupenthixol.
      Neither nisoxetine nor cocaine increased physiological (salivary cortisol) or
      behavioral (self-directed behaviors) markers of stress. These findings suggest
      that NE transporter inhibition and alpha2-adrenoceptor mechanisms play a
      significant role in cocaine-induced reinstatement of drug seeking that is not
      secondary to activation of brain stress pathways.

PMID- 17505019
TI  - Antiepileptic drugs affect neuronal androgen signaling via a cytochrome P450
      dependent pathway.
AB  - Recent data imply an important role for brain cytochrome P450 (P450) in endocrine
      signaling. In epileptic patients, treatment with P450 inducers led to
      reproductive disorders; in mouse hippocampus, phenytoin treatment caused
      concomitant up-regulation of CYP3A11 and androgen receptor (AR). In the present
      study, we established specific in vitro models to examine whether CYP3A isoforms
      cause enhanced AR expression and activation. Murine Hepa1c1c7 cells and neuronal
      type rat PC-12 cells were used to investigate P450 regulation and its effects on
      AR after phenytoin and phenobarbital administration. In both cell lines,
      treatment with antiepileptic drugs (AEDs) led to concomitant up-regulation of
      CYP3A (CYP3A11 in Hepa1c1c7 and CYP3A2 in PC-12) and AR mRNA and protein.
      Inhibition of CYP3A expression and activity by the CYP3A inhibitor ketoconazole
      or by CYP3A11-specific short interfering RNA molecules reduced AR expression to
      basal levels. The initial up-regulation of AR signal transduction, measured by an
      androgen-responsive element chloramphenicol-acetyltransferase reporter gene
      assay, was completely reversed after specific inhibition of CYP3A11. Withdrawal
      of the CYP3A11 substrate testosterone prevented AR activation, whereas AR mRNA
      expression remained up-regulated. In addition, recombinant CYP3A11 was expressed
      heterologously in PC-12 cells, thereby eliminating any direct drug influence on
      the AR. Again, the initial up-regulation of AR mRNA and activity was reduced to
      basal levels after silencing of CYP3A11. In conclusion, we show here that CYP3A2
      and CYP3A11 are crucial mediators of AR expression and signaling after AED
      application. These findings point to an important and novel function of P450 in
      regulation of steroid hormones and their receptors in endocrine tissues such as
      liver and brain.

PMID- 17505020
TI  - Pharmacokinetics and amyloid plaque targeting ability of a novel peptide-based
      magnetic resonance contrast agent in wild-type and Alzheimer's disease transgenic
      mice.
AB  - A novel magnetic resonance (MR) imaging contrast agent based on a derivative of
      human amyloid beta (Abeta) peptide, Gd[N-4ab/Q-4ab]Abeta 30, was previously shown
      to cross the blood-brain barrier (BBB) and bind to amyloid plaques in Alzheimer's
      disease (AD) transgenic mouse (APP/PS1) brain. We now report extensive plasma and
      brain pharmacokinetics of this contrast agent in wild-type (WT) and in APP/PS1
      mice along with a quantitative summary of various physiological factors that
      govern its efficacy. Upon i.v. bolus administration, (125)I-Gd[N-4ab/Q-4ab]Abeta
      30 was rapidly eliminated from the plasma following a three-exponential
      disposition, which is saturable at higher concentrations. Nevertheless, the
      contrast agent exhibited rapid and nonsaturable absorption at the BBB. The brain
      pharmacokinetic profile of (125)I-Gd[N-4ab/Q-4ab]Abeta 30 showed a rapid
      absorption phase followed by a slower elimination phase. No significant
      differences were observed in the plasma or brain kinetics of WT and APP/PS1
      animals. Emulsion autoradiography studies conducted on WT and APP/PS1 mouse brain
      after an i.v. bolus administration of (125)I-Gd[N-4ab/Q-4ab]Abeta 30 in vivo
      confirmed the brain pharmacokinetic data and also demonstrated the preferential
      localization of the contrast agent on the plaques for an extended period of time.
      These attributes of the contrast agent are extremely useful in providing an
      excellent signal/noise ratio during longer MR scans, which may be essential for
      obtaining a high resolution image. In conclusion, this study documents the
      successful plaque targeting of Gd[N-4ab/Q-4ab]Abeta 30 and provides crucial
      pharmacokinetic information to determine the dose, mode of administration, and
      scan times for future in vivo MR imaging of amyloid plaques in AD transgenic
      mice.

PMID- 17505021
TI  - Using an analytic framework to identify potential targets and strategies for
      ecologically based physical activity interventions in middle schools.
AB  - The objective was to demonstrate the value of applying an ecological analytic
      framework to formative data in conjunction with ecological planning frameworks
      (e.g., intervention mapping) to ensure a high degree of ecological program
      integration as illustrated through a physical activity program for students in
      middle school. Eight focus groups were conducted with 38 students in four schools
      to examine student perceptions of who or what in their school made it easy or
      difficult for students to be physically active. Qualitative data were used to
      identify potential intervention targets according to the analytic framework.
      Frequency analysis revealed that most identified physical activity
      barriers/facilitators were associated with organization (59.4%) targets. Five
      different intervention strategies were identified, with organizational
      modification being most popular. Applying the analytic framework to formative
      data enabled us to identify potential targets, strategies, and activities for an
      ecologically based physical-activity-promotion program relevant to the priority
      population.

PMID- 17505022
TI  - Regulation of the microsomal prostaglandin E synthase-1 in polarized mononuclear
      phagocytes and its constitutive expression in neutrophils.
AB  - PGs are potent mediators of pain and inflammation. PGE synthases (PGES) catalyze
      the isomerization of PGH(2) into PGE(2). The microsomal (m)PGES-1 isoform serves
      as an inducible PGES and is responsible for the production of PGE(2), which
      mediates acute pain in inflammation and fever. The present study was designed to
      investigate the regulation of expression of mPGES-1 in polarized phagocytes,
      which represent central, cellular orchestrators of inflammatory reactions. Here,
      we report that human peripheral blood monocytes did not express mPGES-1. Exposure
      to LPS strongly induced mPGES-1 expression. Alternatively activated M2 monocytes
      macrophages exposed to IL-4, IL-13, or IL-10 did not express mPGES-1, whereas in
      these cells, IL-4, IL-13, and to a lesser extent, IL-10 or IFN-gamma inhibited
      LPS-induced, mPGES-1 expression. It is unexpected that polymorphonuclear
      leukocytes expressed high basal levels of mPGES-1, which was up-regulated by LPS
      and down-regulated by IL-4 and IL-13. Induction of mPGES-1 and its modulation by
      cytokines were confirmed at the protein level and correlated with PGE(2)
      production. Cyclooxygenase 2 expression tested in the same experimental
      conditions was modulated in monocytes and granulocytes similarly to mPGES-1.
      Thus, activated M1, unlike alternatively activated M2, mononuclear phagocytes
      express mPGES-1, and IL-4, IL-13, and IL-10 tune expression of this key enzyme in
      prostanoid metabolism. Neutrophils, the first cells to enter sites of
      inflammation, represent a ready-made, cellular source of mPGES-1.

PMID- 17505023
TI  - Induction of a distinct CD8 Tnc17 subset by transforming growth factor-beta and
      interleukin-6.
AB  - Cross-talk between TGF-beta and IL-6 has been shown to direct the differentiation
      of CD4(+) cells into special IL-17-secreting cells, which are termed Th17 cells.
      In this study, we demonstrated that TGF-beta and IL-6 could stimulate CD8(+)
      cells to differentiate into noncytotoxic, IL-17-producing cells in MLC. These IL
      17-producing CD8(+) cells exhibit a unique granzyme B(-)IFN-gamma(-)IL-10(-)
      phenotype. The mRNA level of Th2/T cytotoxic 2 (Tc2) transcription factors GATA3
      and Th1/Tc1 transcription factors T-box expressed in T cell (T-bet) as well as
      its target H2.O-like homeobox (Hlx) is decreased in CD8(+) cells from TGF-beta-
      and IL-6-treated MLC. In addition, these CD8(+) cells display a marked up
      regulation of retinoic acid-related orphan receptor-gammat, a key IL-17
      transcription factor. These results demonstrate that the existence of an IL-17
      producing CD8(+) subset belongs to neither the Tc1 nor the Tc2 subset and can be
      categorized as a T noncytotoxic 17 (Tnc17) subset.

PMID- 17505024
TI  - Adenosine A2a receptor-mediated, normoxic induction of HIF-1 through PKC and PI
      3K-dependent pathways in macrophages.
AB  - Adenosine released by cells in injurious or hypoxic environments has tissue
      protecting and anti-inflammatory effects, which are also a result of modulation
      of macrophage functions, such as vascular endothelial growth factor (VEGF)
      production. As VEGF is a well-known target of hypoxia-inducible factor 1 (HIF-1),
      we hypothesized that adenosine may activate HIF-1 directly. Our studies using
      subtype-specific adenosine receptor agonists and antagonists showed that by
      activating the A(2A) receptor, adenosine treatment induced HIF-1 DNA-binding
      activity, nuclear accumulation, and transactivation capacity in J774A.1 mouse
      macrophages. Increased HIF-1 levels were also found in adenosine-treated mouse
      peritoneal macrophages. The HIF-1 activation induced by the A(2A) receptor
      specific agonist CGS21680 required the PI-3K and protein kinase C pathways but
      was not mediated by changes in iron levels. Investigation of the molecular basis
      of HIF-1 activation revealed the involvement of transcriptional and to a larger
      extent, translational mechanisms. HIF-1 induction triggered the expression of HIF
      1 target genes involved in cell survival (aldolase, phosphoglycerate kinase) and
      VEGF but did not induce inflammation-related genes regulated by HIF-1, such as
      TNF-alpha or CXCR4. Our results show that the formation of adenosine and
      induction of HIF-1, two events which occur in response to hypoxia, are linked
      directly and suggest that HIF-1 activation through A(2A) receptors may contribute
      to the anti-inflammatory and tissue-protecting activity of adenosine.

PMID- 17505025
TI  - Comparison of peak expiratory flow variability between workers with work
      exacerbated asthma and occupational asthma.
AB  - BACKGROUND: Peak expiratory flow (PEF) monitoring is frequently used to diagnose
      occupational asthma (OA). The variability of PEF between periods at work and away
      from work has not been described in workers with work-exacerbated asthma (WEA).
      We sought to assess and compare the diurnal variability of PEF during periods at
      and away from work between subjects with OA and WEA. METHODS: Workers referred
      for work-related asthma underwent PEF monitoring for 2 weeks at and away from
      work. The diagnostic of OA or WEA was subsequently made according to the
      respective positivity or negativity of the specific inhalation challenges. PEF
      mean diurnal variability was calculated during periods at and away from work. PEF
      graphs were also interpreted using direct visual analysis by five observers and
      using a computer program (Oasys-2, Expert System ) [available at:
      http://www.occupationalasthma.com]. RESULTS: Thirty-four subjects were
      investigated (WEA, n = 15; OA, n = 19). There was a greater variability of PEF at
      work than away from work in both OA (19.8 +/- 8.7% vs 10.7 +/- 6.3%, p < 0.001)
      and WEA (14.2 +/- 4.8% vs 10.6 +/- 5.6%, p = 0.02). However, the magnitude of the
      variability was higher in OA than in WEA (p = 0.02). The visual interpretation of
      PEF or the Oasys-2 program failed to distinguish WEA from OA. CONCLUSION:
      Although workers with OA showed a higher PEF variability than workers with WEA
      when at work, clinicians were unable to reliably differentiate OA from WEA using
      the visual interpretation of PEF graphs or the computerized analysis.

PMID- 17505026
TI  - Pneumonia severity index class v patients with community-acquired pneumonia:
      characteristics, outcomes, and value of severity scores.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) with a pneumonia severity index
      (PSI) score in risk class V (PSI-V) is a potentially life-threatening condition,
      yet the majority of patients are not admitted to the ICU. The aim of this study
      was to characterize CAP patients in PSI-V to determine the risk factors for ICU
      admission and mortality, and to assess the performance of CAP severity scores in
      this population. METHODS: Prospective observational study including hospitalized
      adults with CAP in PSI-V from 1996 to 2003. Clinical and laboratory data,
      microbiological findings, and outcomes were recorded. The PSI score; modified
      American Thoracic Society (ATS) score; the confusion, urea, respiratory rate, low
      BP (CURB) score, and CURB plus age of >/= 65 years score were calculated. A
      reduced score based on the acute illness variables contained in the PSI was also
      obtained. RESULTS: A total of 457 patients were included in the study (mean [+/-
      SD] age, 79 +/- 11 years), of whom 92 (20%) were admitted to the ICU. Patients in
      the ward were older (mean age, 82 +/- 10 vs 70 +/- 10 years, respectively) and
      had more comorbidities. ICU patients experienced significantly more acute organ
      failures. The mortality rate was higher in ICU patients, but also was high for
      non-ICU patients (37% vs 20%, respectively; p = 0,003). A low level of
      consciousness (odds ratio [OR], 3.95; 95% confidence interval [CI], 2 to 5) and
      shock (OR, 24.7; 95% CI, 14 to 44) were associated with a higher risk of death.
      The modified ATS severity rule had the best accuracy in predicting ICU admission
      and mortality. CONCLUSIONS: Most CAP patients PSI-V were treated on a hospital
      ward. Those admitted to the ICU were younger and had findings of more acute
      illness. The PSI performed well as a mortality prediction tool but was less
      appropriate for guiding site-of-care decisions.

PMID- 17505027
TI  - Analyzing the short-term effect of placebo therapy in pulmonary arterial
      hypertension: potential implications for the design of future clinical trials.
AB  - BACKGROUND: Placebo is commonly used in short-term randomized trials for
      pulmonary arterial hypertension (PAH). Currently, outcome data regarding placebo
      are lacking. We conducted a systematic review and performed a metaanalysis to
      assess its effect. METHODS: Articles were identified via a query of MEDLINE and
      EMBASE using the following terms: "pulmonary hypertension"; "clinical trial";
      "six minute walk"; "pulmonary hemodynamic"; and "survival." A manual bibliography
      search of selected trials, reviews, and guidelines was performed. The inclusion
      criteria were as follows: randomized, placebo-controlled with data reported at
      baseline and at 12 to 18 weeks. Two reviewers independently abstracted: 6-min
      walk distance, pulmonary hemodynamic measures and frequency of death, clinical
      worsening, and change in New York Heart Association/World Health Organization
      functional class. The data were pooled using a random-effects model. RESULTS:
      Thirteen of the 688 articles identified met the inclusion criteria (a total of
      868 placebo-treated patients). After 12 to 18 weeks, the 6-min walk distance
      decreased by 8.4 m (95% confidence interval [CI], -14.6 to -2.2) and pulmonary
      vascular resistance increased by 58.9 dyne (.) s (.) cm(-5) (95% CI, 27.6 to
      90.1). Placebo-treated patients were 1.81 times more likely to experience a
      clinical worsening (95% CI, 1.30 to 2.53). Placebo treatment was not associated
      with a difference in mortality. CONCLUSIONS: Patients with PAH who receive
      placebo are more likely to experience clinical deteriorations. Further debate is
      needed regarding the design of future clinical trials. Research efforts should
      focus on evaluating existing medications against one another and comparing novel
      therapies with currently accepted ones.

PMID- 17505028
TI  - Association of RBC transfusion with mortality in patients with acute lung injury.
AB  - BACKGROUND: RBC transfusion has been associated with increased morbidity and
      mortality in a variety of clinical settings. We assessed the effect of RBC
      transfusion on in-hospital mortality in patients with acute lung injury (ALI).
      METHODS: Cohort study of 248 consecutive patients with ALI. RBC transfusion was
      evaluated as both dichotomous and continuous variables, with outcome being in
      hospital mortality adjusted for clinical confounders and length of total hospital
      stay. RESULTS: Overall in-hospital mortality rate was 39.5%. Of these patients,
      207 of 248 patients (83.5%) received > or = 1 U of packed RBCs. The transfusion
      of any packed RBCs was associated with an increased risk of death (adjusted odds
      ratio [OR], 3.12; 95% confidence interval [CI], 1.28 to 7.58; p < 0.001). The
      overall OR per unit was 1.06 (95% CI, 1.04 to 1.09; p < 0.001) in the complete
      multivariable model. Transfusion after ALI onset was associated with an adjusted
      OR of 1.13 (95% CI, 1.07 to 1.20; p < 0.001), while transfusion before ALI onset
      was not associated with higher risk. The adjusted OR per unit of nonleukoreduced
      RBC transfused was 1.14 (95% CI, 1.07 to 1.21; p < 0.001), while the adjusted OR
      for leukoreduced cells per unit transfused was 1.06 (95% CI, 1.03 to 1.09; p <
      0.001). CONCLUSIONS: Transfusion of RBCs in patients with ALI was associated with
      increased in-hospital mortality. This risk occurred with RBC transfusion after
      the onset of ALI, and was greater for nonleukoreduced than for leukoreduced RBCs.
      Aggressive transfusion strategies in patients with established ALI should be
      questioned, pending further study.

PMID- 17505029
TI  - Usefulness of whole-blood interferon-gamma assay and interferon-gamma enzyme
      linked immunospot assay in the diagnosis of active pulmonary tuberculosis.
AB  - PURPOSES: The aim of this study was to evaluate the usefulness of the whole-blood
      interferon-gamma assay (enzyme-linked immunosorbent assay [ELISA]) and interferon
      gamma enzyme-linked immunospot assay (ELISPOT) based on early secretory antigenic
      target 6 and culture filtrate protein 10 in the diagnosis of active pulmonary
      tuberculosis (TB) in routine clinical practice. METHOD: We conducted a
      prospective study enrolling 144 participants with suspected pulmonary TB in a
      tertiary referral hospital in Seoul, South Korea, to investigate the diagnostic
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) of these tests. Clinical assessment, tuberculin skin test
      (TST), whole-blood interferon-gamma ELISA (QuantiFERON-TB Gold [QFT-G]; Cellestis
      Ltd; Victoria, Australia), and an ELISPOT assay (T SPOT.TB; Oxford Immunotec;
      Oxford, UK) were performed. Test results were compared with the final confirmed
      diagnoses. RESULTS: Active pulmonary TB was diagnosed in 67 of 144 participants
      (47%). Sensitivities of QFT-G and T SPOT.TB for active pulmonary TB were 89% (95%
      confidence interval [CI], 79 to 96%) and 92% (95% CI, 83 to 97%), respectively;
      and specificities were 49% (95% CI, 37 to 61%) and 47% (95% CI, 36 to 59%). NPVs
      of QFT-G (84%; 95% CI, 69 to 93%) and T SPOT.TB (87%; 95% CI, 73 to 96%) were
      higher than that of TST (64%; 95% CI, 51 to 76%) [p = 0.001 and p < 0.001,
      respectively]. CONCLUSION: High NPVs of QFT-G and T SPOT.TB for the diagnosis of
      active TB suggest the supplementary role of these tests for the diagnostic
      exclusion of active TB, although the low PPV limits their usefulness in routine
      clinical practice in South Korea, where the prevalence of latent TB infection is
      considerable.

PMID- 17505030
TI  - Upstaging by vessel invasion improves the pathology staging system of non-small
      cell lung cancer.
AB  - BACKGROUND: There is a need for a more complete classification system of lung
      cancer. To address this issue, we assessed whether the new staging could
      differentiate patients with early-stage cancers who have poorer prognosis and
      improve the unbalanced patient numbers with overlapping prognoses arising from
      the current TNM staging system. METHODS: The study included 995 patients with
      pathology stages I and II non-small cell lung cancer (NSCLC) who underwent
      surgical resection at two institutions. We subclassified patients with stage IA
      and IB NSCLC based on the presence of vessel invasion (Vi). Stage IA Vi and stage
      IB non-Vi were combined into new stage IB, as were stages IB Vi and IIA into new
      stage IIA. RESULTS: The numbers of patients of stages IA, IB, IIA, and IIB were
      477, 314, 55, and 149, and their 5-year survival rates were 86.0%, 66.2%, 60.7%,
      and 50.4%, respectively. Vi groups showed significantly poorer prognosis than non
      Vi groups at stage IA (p = 0.011) and at stage IB (p = 0.036). The numbers of
      patients of new stages IA, IB, and IIA were 333, 260, and 253, and their 5-year
      survival rates were 88.7%, 76.4%, and 61.2%, respectively. Regression analysis
      indicated that the new staging improved predictability of overall survival
      according to disease stage, and Akaike information criterion (3023.7) was
      significantly lower than that for current staging system (3032.5). CONCLUSION:
      Upstaging of Vi groups allows differentiation of patients with early-stage
      cancers with poor prognosis and improves the unbalanced numbers of patients and
      prediction of prognosis in cases of lung cancer.

PMID- 17505031
TI  - Long-term survival following pneumonectomy for non-small cell lung cancer:
      clinical implications for follow-up care.
AB  - BACKGROUND: The aim of this study was to determine the risk of overall death in
      long-term survivors (> 5 years) after pneumonectomy for non-small cell lung
      cancer (NSCLC), and to establish the optimal follow-up strategy for these
      patients. METHODS: We analyzed a single-center experience with 94 long-term
      survivors who underwent pneumonectomy (group A) for NSCLC between January 1992
      and December 2000. Prospective tumor registry data were compared with data for
      147 long-term survivors who underwent lobectomy (group B) during the same period.
      RESULTS: Clinical characteristics at the time of operation differed between the
      two groups with more squamous histology, larger tumor size, and more advanced
      stage in group A compared with group B. During follow-up, late lung cancer
      relapses were rare in both groups (2.1% vs 1.4%), and second primary malignancies
      were less frequent in group A (2.1% vs 9.5%, p = 0.032). The overall 10-year
      survival rate was lower in group A than in group B (67.3% vs 82.8%); however,
      there was no significant difference in lung cancer-specific survival (93.5% vs
      95.1%). Intercurrent disease was the leading cause of death in group A (14
      patients, 14.9%), most commonly respiratory failure resulting from community
      acquired pneumonia. CONCLUSION: Late cancer relapse or second primary
      malignancies were rare in long-term survivors after pneumonectomy, but the
      overall mortality remained high as a result of intercurrent diseases. Continued
      surveillance should focus on prevention, early detection and aggressive
      management of intercurrent disease during follow-up care of these patients.

PMID- 17505032
TI  - Replacement of the 6-min walk test with maximal oxygen consumption in the BODE
      Index applied to patients with COPD: an equivalency study.
AB  - INTRODUCTION: Patients with COPD have decreased exercise capacity and low oxygen
      consumption (Vo(2)) during formal cardiopulmonary exercise testing, and lower
      scores on health-related quality of life questionnaires. When isolated, these
      three variables show different correlations with COPD mortality. The
      multidimensional BODE (body mass index[BMI], airflow obstruction, dyspnea, and
      exercise capacity in COPD) index, which comprises four variables including the 6
      min walk test (6MWT), predicts survival in COPD. OBJECTIVES: To evaluate the
      degree of association between the values of the BODE index using the 6MWT with
      the BODE index using maximal Vo(2) (Vo(2)max) obtained in a maximal incremental
      test. MATERIALS AND METHODS: Fifty patients with mild-to-severe COPD (average
      age, 63.5 +/- 9.9 years; FEV(1), 65.3 +/- 23.6% of predicted) [+/- SD] had BMI,
      spirometric function (FVC and FEV(1)), and dyspnea status (Medical Research
      Council) evaluated. Two BODE index scores were then completed: one with the 6MWT,
      and one with the Vo(2)max obtained during maximal incremental testing on a
      treadmill. RESULTS: Correlation between BODE index and Vo(2) in milliliters per
      minute per kilogram (r = - 0.41) was weak; the correlation was moderate (r = -
      0.64) when Vo(2) percentage of predicted was used. The BODE index modified by
      replacing the 6MWT with Vo(2) showed excellent correlations with Vo(2) in
      milliliters per minute per kilogram (r = 0.92) and Vo(2) percentage of predicted
      (r = 0.95). CONCLUSION: The excellent correlation between the conventional BODE
      index and the modified BODE index with Vo(2) replacing the 6MWT enables us to
      reach the conclusion that the original BODE index is very effective in the
      evaluation of COPD patients.

PMID- 17505033
TI  - Sex differences in the prevalence of psychiatric disorders and psychological
      distress in patients with COPD.
AB  - BACKGROUND: Psychiatric disorders are highly prevalent in patients with COPD. In
      general, psychiatric disorders are more common in women than in men. The extent
      to which women with COPD suffer from greater psychiatric and psychological
      morbidity is not known. The present cross-sectional study evaluated the
      prevalence of mood and anxiety disorders, levels of psychological distress, and
      quality of life in 62 women and 54 men with documented, stable COPD. METHODS: All
      patients (n = 116) underwent a sociodemographic and medical history interview,
      followed by a structured psychiatric interview and standard spirometry. Patients
      also completed a battery of questionnaires measuring psychological distress and
      quality of life. RESULTS: The overall prevalence of psychiatric disorders was
      49%. Significantly more women than men met the diagnostic criteria for anxiety
      disorders (56% vs 35%), and a trend for greater levels of major depression in
      women was found (18% vs 7%). Women had significantly higher anxiety sensitivity
      and depressive symptoms compared to men but did not report more limitations in
      psychological functioning. Women also reported being less confident in their
      ability to control respiratory symptoms, and more daily physical limitations
      compared to men, despite having comparable COPD severity, dyspnea scores, and
      exacerbation rates. CONCLUSIONS: Results indicate that psychiatric disorders are
      at least three times higher in COPD patients compared to the general population,
      and nearly two times higher in women than in men. Women also have greater
      psychological distress, worse perceived control of symptoms, and greater
      functional impairment. Greater efforts should be made to identify and treat
      psychiatric disorders in COPD patients, particularly in women.

PMID- 17505034
TI  - CD4-regulatory cells in COPD patients.
AB  - BACKGROUND: The numbers of airway CD8 and B lymphocytes are increased in COPD
      patients, suggesting an autoimmune process. CD4-regulatory T cells control
      autoimmunity but have not been studied in patients with COPD. OBJECTIVE: To
      compare T-regulatory cell numbers in the BAL from COPD patients, smokers with
      normal lung function, and healthy nonsmokers (HNS). METHODS: BAL and peripheral
      blood mononuclear cell (PBMC) samples were obtained from 26 COPD patients, 19
      smokers, and 8 HNS. Flow cytometry was performed for regulatory phenotypic
      markers. RESULTS: COPD patients had increased BAL CD8 numbers compared to smokers
      and HNS. CD4 numbers were similar between groups. There was increased BAL
      CD4CD25(bright) expression in smokers (median 28.8%) and COPD patients (median
      23.1%) compared to HNS (median 0%). Increased FoxP3 expression was confirmed in
      BAL CD4CD25(bright) cells. BAL CD4CD25 cells expressed less CD27 compared to
      PBMCs, suggesting weaker functional regulatory ability. CLINICAL IMPLICATIONS:
      Chronic cigarette smoke exposure up-regulates airway CD4 regulatory cell numbers.
      Their function may be to control pulmonary inflammation.

PMID- 17505035
TI  - Cystic lung disease in Birt-Hogg-Dube syndrome.
AB  - BACKGROUND: To describe the clinical, radiologic, and histopathologic aspects of
      cystic lung disease occurring in patients with Birt-Hogg-Dube (BHD) syndrome, a
      rare, inheritable, multisystem disorder. METHODS: We retrospectively reviewed
      five patients with BHD syndrome evaluated at the Mayo Clinic Rochester from 1998
      through 2005. RESULTS: Mean age (+/- SD) at the time of pulmonary evaluation was
      56.4 +/- 4.8 years; four patients were men. Three patients had not received a
      diagnosis of BHD syndrome at the time of initial CT of the chest. Three patients
      had a smoking history, and two were nonsmokers. Two patients had a history of
      recurrent pneumothoraces. Pulmonary function tests available in four patients
      revealed normal results in one patient and mild airflow obstruction or
      nonspecific pattern of abnormalities in three patients. CT of the chest revealed
      cystic lung disease in all five patients; cysts were round to oval in shape,
      ranged widely in size, and were randomly distributed throughout the lungs, except
      for a predilection to involve the lung bases more extensively. Three patients
      with a smoking history had more severe cystic changes compared to nonsmokers and
      included both patients with recurrent pneumothoraces. Surgical lung biopsy
      available in one patient revealed emphysema-like changes. Follow-up CT scans
      available in four patients revealed relative stability over a median interval of
      20 months (range, 3 to 66 months). CONCLUSION: We conclude that cystic lung
      disease in BHD syndrome varies widely in severity, mimics pulmonary
      lymphangioleiomyomatosis, and may be worsened by smoking.

PMID- 17505036
TI  - Natural history of stage I non-small cell lung cancer: implications for early
      detection.
AB  - BACKGROUND: Concern has been raised that early detection of lung cancer may lead
      to the treatment of clinically indolent cancers. No population-based study has
      examined the natural history of patients with stage I NSCLC who receive no
      surgery, chemotherapy, or radiation therapy. Our hypothesis is that long-term
      survival in patients with untreated stage I non-small cell lung cancer (NSCLC) is
      uncommon. METHODS: A total of 101,844 incident cases of NSCLC in the California
      Cancer Center registry between 1989 and 2003 were analyzed; 19,702 patients had
      stage I disease, of whom 1,432 did not undergo surgical resection or receive
      treatment with chemotherapy or radiation. Five-year overall survival (OS) and
      lung cancer-specific survival were determined for this untreated group, for
      subsets of patients who were recommended but refused surgical resection, and for
      T1 tumors. RESULTS: Only 42 patients with untreated stage I NSCLC were alive 5
      years after diagnosis. Five-year OS for untreated stage I NSCLC was 6% overall,
      9% for T1 tumors, and 11% for patients who refused surgical resection. Five-year
      lung cancer-specific survival rates were 16%, 23%, and 22%, respectively. Among
      these untreated patients, median survival was 9 months overall, 13 months for
      patients with T1 disease, and 14 months for patients who refused surgical
      resection. CONCLUSION: Long-term survival with untreated stage I NSCLC is
      uncommon, and the vast majority of untreated patients die of lung cancer. Given
      that median survival is only 13 months in patients with T1 disease, surgical
      resection or other ablative therapies should not be delayed even in patients with
      small lung cancers.

PMID- 17505037
TI  - Comparison of percentage fall in FVC at the provocative concentration of
      methacholine causing a 20% fall in FEV(1) between patients with asymptomatic
      bronchial hyperresponsiveness and mild asthma.
AB  - BACKGROUND: A significant proportion of individuals who have no symptoms of
      asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR).
      BHR is usually assessed by measuring the provocative concentration of
      methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at
      the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and
      to be a more useful index of disease severity in asthma than PC(20). The aim of
      this study was to investigate whether asymptomatic BHR would differ from
      symptomatic BHR with regard to DeltaFVC. METHODS: Methacholine bronchial
      challenge tests were conducted in children with no past or current symptoms of
      asthma, allergic rhinitis, or other respiratory diseases, who were identified
      among siblings of children with asthma. Forty-three children with asymptomatic
      BHR (PC(20) < 16 mg/mL) were recruited, and 43 children with mild asthma who were
      matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC
      on methacholine concentration-response curves was retrospectively analyzed in the
      two groups. RESULTS: There were no differences in the frequency of atopy, blood
      eosinophil counts, serum IgE levels, and spirometric values between the
      asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly
      (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild
      asthma group (16.9 +/- 4.3%). CONCLUSIONS: Our results suggest that children with
      asymptomatic BHR have a lower level of maximal airway response than mild
      asthmatics with a similar degree of BHR. This may be a possible explanation for
      the lack of symptoms in subjects with asymptomatic BHR.

PMID- 17505038
TI  - Sleep-disordered breathing and uric acid in overweight and obese children and
      adolescents.
AB  - OBJECTIVE: The aim of this study was to determine whether the severity of sleep
      disordered breathing (SDB) was associated with increased levels of uric acid
      (UA), both in serum and in urine, as a marker of tissue hypoxia, in a sample of
      overweight and obese subjects, irrespective of indexes of adiposity. METHODS:
      Consecutive subjects underwent polysomnography, fasting blood sampling, and 24-h
      urine collection. Outcome parameters were serum UA, UA excretion ([24-h urinary
      UA x serum creatinine]/urine creatinine) and urinary UA/creatinine ratio.
      RESULTS: A total of 93 subjects were included (44% boys; mean [+/- SD] age = 11.1
      +/- 2.5; 73% obese). A fasting measurement of serum UA levels was available for
      62 patients. The respiratory disturbance index was a significant covariate (beta
      = 0.09 +/- 0.03; p = 0.01) in the regression model for serum UA, controlling for
      sex (beta = 0.32 +/- 0.29; p = 0.3), puberty (beta = 0.87 +/- 0.34; p = 0.01),
      and waist circumference (beta = 0.04 +/- 0.01; p = 0.005). The percentage of
      total sleep time with arterial oxygen saturation < or = 89% (beta = 0.94 +/-
      0.45; p = 0.04) was also significantly associated with serum UA level,
      controlling for sex (beta = 0.22 +/- 0.30; p = 0.5), puberty (beta = 0.83 +/-
      0.35; p = 0.02), and waist circumference (beta = 0.04 +/- 0.02; p = 0.02). None
      of the SDB variables correlated with UA excretion or with urinary UA/creatinine
      ratio. CONCLUSION: This study in overweight children and adolescents demonstrated
      a relationship between the severity of sleep apnea and increased levels of serum
      UA, independent of abdominal adiposity. In view of the known associations between
      UA and cardiovascular risk, this finding may contribute to the mechanisms linking
      SDB with cardiovascular morbidity.

PMID- 17505039
TI  - Serum angiopoietin-2 as a clinical marker for lung cancer.
AB  - BACKGROUND: Angiopoietins play a critical role in the angiogenesis related to
      tumor growth in concert with vascular endothelial growth factor (VEGF), and
      enhanced expression of angiopoietin-2 has been reported in lung cancer tissue.
      METHODS: Patients with lung cancer (n = 136) and healthy volunteers (n = 40) were
      enrolled. Serum angiopoietin-2 and VEGF concentrations were measured using enzyme
      linked immunosorbent assay. RESULTS: Patients with lung cancer had higher serum
      angiopoietin-2 (2,046.3 +/- 1,171.3 pg/mL vs 1,269.8 +/- 494.1 pg/mL, p < 0.001)
      and VEGF (542.9 +/- 445.8 pg/mL vs 364.7 +/- 185.9 pg/mL, p < 0.05) [mean +/- SD]
      levels than the control group. Serum angiopoietin-2 and VEGF levels correlated
      with each other in patients with lung cancer (Spearman r = 0.30, p < 0.001),
      specifically in non-small cell lung cancer (NSCLC) [n = 110; r = 0.34; p < 0.001]
      but not in small cell lung cancer (n = 26). With stage progression in NSCLC,
      serum angiopoietin-2 levels increased, and patients with distant metastasis had
      higher levels than those without metastasis (p < 0.005). By contrast, serum VEGF
      level did not increase with stage progression, and only had a trend toward
      elevation in distant metastasis (p = 0.05). In NSCLC, the low angiopoietin-2
      group (< 1,605.5 pg/mL) had a better overall survival compared to the high
      angiopoietin-2 group (> or = 1,605.5 pg/mL; p < 0.05), although this survival
      benefit was not maintained after controlling for stage in a multivariate
      analysis. The angiopoietin-2 levels were higher in NSCLC patients with
      postoperative recurrence than in those without. CONCLUSIONS: Our study suggests
      that serum angiopoietin-2 is a useful clinical marker for detecting NSCLC with
      distant metastasis and is of potential prognostic value.

PMID- 17505040
TI  - Safety of inferior vena cava filter retrieval in anticoagulated patients.
AB  - PURPOSES: To evaluate the safety of inferior vena cava (IVC) filter retrieval in
      therapeutically anticoagulated patients in comparison to prophylactically or not
      therapeutically anticoagulated patients with respect to retrieval-related
      hemorrhagic complications. MATERIALS AND METHODS: This was a retrospective study
      of 115 consecutive attempted IVC filter retrievals in 110 patients. Filter
      retrievals were stratified as performed in patients who were therapeutically
      anticoagulated (group 1), prophylactically anticoagulated (group 2), or not
      therapeutically anticoagulated (group 3). The collected data included
      anticoagulant and antiplatelet medications (type, form and duration of
      administration, dosage) at the time of retrieval. Phone interviews and chart
      review was performed for the international normalized ratio (INR), activated
      partial thromboplastin time, platelet count, infusion of blood products, and
      retrieval-related hemorrhagic complications. RESULTS: Group 1 included 65
      attempted filter retrievals in 61 therapeutically anticoagulated patients by
      measured INR or dosing when receiving low-molecular-weight heparin (LMWH). Four
      retrievals were not successful. In patients receiving oral anticoagulation, the
      median INR was 2.35 (range, 2 to 8). Group 2 comprised 23 successful filter
      retrievals in 22 patients receiving a prophylactic dose of LMWH. Group 3 included
      27 attempted filter retrievals in 27 patients not receiving therapeutic
      anticoagulation. Six retrievals were not successful. Five patients were receiving
      oral anticoagulation with a subtherapeutic INR (median, 1.49; range, 1.16 to
      1.69). No anticoagulation medication was administered in 22 patients. In none of
      the groups were hemorrhagic complications related to the retrieval procedures
      identified. CONCLUSIONS: These results suggest that retrieval of vena cava
      filters in anticoagulated patients is safe. Interruption or reversal of
      anticoagulation for the retrieval of vena cava filters is not indicated.

PMID- 17505041
TI  - Effect of biventricular pacing on the exercise pathophysiology of heart failure.
AB  - BACKGROUND: Biventricular pacing (BVP) is used for cardiac resynchronization
      therapy in wide-QRS-complex heart failure. We sought to quantify the effect of
      BVP on the exercise pathophysiology of heart failure patients. METHODS: Using
      cardiopulmonary exercise testing, we analyzed exercise data for a multicenter
      study sponsored by St. Jude Medical. Patients had pacemaker electrodes implanted
      in both ventricles in the standard manner and were randomized by St. Jude before
      exercise testing. Exercise measurements included peak oxygen uptake (Vo(2)), peak
      O(2) pulse, anaerobic threshold (AT), and ventilatory equivalent for CO(2)
      (reflecting change in peak exercise cardiac output, stroke volume, maximal
      sustainable exercise capacity, and ventilation-perfusion mismatching,
      respectively) at baseline and at a 6-month follow-up. The studies included
      progressively and uniformly increasing work rate to maximum tolerance. The
      investigators were blinded both to sponsor-controlled randomization and pacemaker
      status. There were 239 paired 6-month studies, as follows: 47 studies served as
      the control with the pacemaker off (ie, the BVP-OFF group); and 192 patients
      received pacing (ie, the BVP-ON group). RESULTS: The BVP-ON group significantly
      improved in all exercise parameters in contrast to the control group (p <
      0.0001). When baseline measurements for the BVP-ON group were ranked in
      quintiles, only patients in the three functionally worst quintiles improved
      significantly at 6 months (peak Vo(2) < 11.6 mL/min/kg, AT < 7.6 mL/min/kg, peak
      O(2) pulse < 12.0 mL/beat, and minute ventilation/Vco(2) ratio at AT > 38.1) [p <
      0.01 to < 0.0001]. CONCLUSION: BVP benefited aerobic function and ventilation
      perfusion mismatching most in those patients with the greatest physiologic
      impairment.

PMID- 17505042
TI  - A pilot study of narrow-band imaging compared to white light bronchoscopy for
      evaluation of normal airways and premalignant and malignant airways disease.
AB  - BACKGROUND: The objectives of this study were to characterize the appearance of
      normal, dysplastic, and frankly malignant airway lesion appearance under narrow
      band imaging (NBI), and to determine if NBI, when used in conjunction with white
      light (WL) bronchoscopy, could improve detection of dysplasia and malignancy.
      PATIENTS AND METHODS: This was a prospective, partially blinded study at a
      university teaching hospital. Bronchoscopy was performed on 22 patients with
      known or suspected bronchial dysplasia or malignancy. Full airway examination was
      performed first under WL bronchoscopy and then under NBI. Directed endobronchial
      biopsies of likely dysplastic, malignant, and normal (control) areas were then
      performed and sent for examination by a pathologist blinded to the gross
      description of the lesion. Pathology interpretations were then compared to the
      corresponding WL and NBI images. RESULTS: There were one malignant and four
      dysplastic lesions in 22 patients detected by NBI when findings by WL imaging
      were considered normal. In cases when the WL appearance was abnormal, NBI did not
      improve the diagnostic yield. The increased rate of detection of dysplasia and
      malignancy by NBI was statistically significant (p = 0.005). CONCLUSION: NBI
      identified dysplasia or malignancy that was not detected by WL inspection in 23%
      of subjects. Further studies are needed to determine the efficacy of NBI in
      detection of premalignant airways lesions in an at-risk population.

PMID- 17505043
TI  - Body mass and fat-free mass indices in COPD: relation with variables expressing
      disease severity.
AB  - BACKGROUND: COPD primarily affects the lungs but also produces systemic
      consequences that are not reflected by the recent staging according to Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Body mass
      index (BMI) and fat-free mass index (FFMI) represent different aspects of
      nutrition abnormalities in COPD. We investigated whether BMI and FFMI could be
      related to parameters expressing airflow obstruction and limitation, exercise
      capacity, airway inflammation, and quality of life, and whether they would
      reflect the GOLD staging of the disease. METHODS: One hundred patients with
      clinically stable COPD equally classified into the five stages of the disease
      were evaluated for BMI, FFMI (measured by bioelectrical impedance analysis),
      airway obstruction and hyperinflation (FEV(1), FEV(1)/FVC, inspiratory capacity),
      exercise capacity (6-min walk distance [6MWD], Borg scale before and after
      6MWD]), chronic dyspnea using the Medical Research Council (MRC) scale, airway
      inflammation (sputum differential cell counts, leukotriene B(4) in supernatant),
      and quality of life (emotional part of the chronic respiratory disease
      questionnaire). RESULTS: 6MWD was significantly associated with both BMI and FFMI
      values, while FFMI additionally presented significant correlations with MRC
      scale, percentage of predicted FEV(1), and FEV(1)/FVC ratio. No association was
      observed between the two nutritional indexes. BMI was not statistically different
      among patients in the five stages of COPD, while FFMI reflected the staging of
      the disease, presenting the highest values in stage 0. CONCLUSIONS: Nutritional
      status is mainly related to exercise capacity. FFMI seems to be more accurate in
      expressing variables of disease severity, as well as the current staging compared
      to BMI.

PMID- 17505044
TI  - Soluble triggering receptor expressed on myeloid cell-1 is increased in patients
      with ventilator-associated pneumonia: a preliminary report.
AB  - RATIONALE: The diagnosis of ventilator-associated pneumonia (VAP) can be
      difficult. Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) has
      been reported to be elevated in BAL fluid from patients with VAP. OBJECTIVES: To
      evaluate the utility of sTREM-1 in the diagnosis of VAP in BAL fluid and the
      fluid collected in the expiratory trap from the ventilator, the exhaled
      ventilator condensate (EVC). METHODS: We prospectively collected BAL fluid and
      EVC from 23 patients clinically suspected of having VAP. A sensitive enzyme
      linked immunosorbent assay was developed to measure sTREM-1. The results derived
      from this assay were confirmed using an immunoblot technique. The presence of VAP
      was clinically determined using a modified clinical pulmonary infection score of
      > 6. RESULTS: VAP was diagnosed in 14 of 23 patients. sTREM-1 was detected in the
      EVC from 11 of 14 subjects with VAP, but from only 1 of 9 subjects without VAP,
      and was significantly higher in the pneumonia patients and when expressed as
      picograms per milliliter or picograms per microgram protein (p = 0.005, both
      comparisons). In contrast, sTREM-1 was detected in the BAL fluid of all 14 VAP
      subjects but also in 8 of 9 subjects with no pneumonia, and did not differ in the
      VAP subjects compared to the nonpneumonia subjects when expressed as picrograms
      per milliliter or picograms per microgram protein (p > 0.05 both comparisons).
      CONCLUSION: sTREM-1 is detectable in EVC and may be useful in establishing or
      excluding the diagnosis of VAP.

PMID- 17505045
TI  - Right ventricular pressure waveform and wave reflection analysis in patients with
      pulmonary arterial hypertension.
AB  - BACKGROUND: Cardiac index is an important determinant of outcome in patients with
      idiopathic pulmonary artery hypertension (IPAH). An implantable hemodynamic
      monitor (IHM) [Chronicle; Medtronic; Minneapolis, MN; a system limited to
      investigational use only] that records right ventricular (RV) pressure waveforms
      continuously may increase our understanding of IPAH and improve therapeutic
      selections and outcomes. The aim of this study was to investigate whether the RV
      pressure waveform utilizing an IHM can be used to estimate the magnitude of
      pressure wave reflection and cardiac index in patients with IPAH in acute
      settings. METHODS: In eight patients with pulmonary arterial hypertension, RV
      pressure waveforms were recorded utilizing the IHM, and breath-by-breath cardiac
      index was recorded during acute IV epoprostenol infusion at 3, 6 and 9 ng/kg/min.
      Late systolic pressure augmentation and cardiac index were estimated using the RV
      pressure waveforms and correlated with direct measurement of cardiac index.
      RESULTS: At baseline, the cardiac index was 2.1 +/- 0.2 L/min/m(2), total
      pulmonary resistance index was 38 +/- 2 Wood U/m(2), and RV systolic pressure was
      92 +/- 4 mm Hg. Wave reflection accounted for 29 +/- 1 mm Hg of the RV systolic
      pressure. During epoprostenol infusion, total pulmonary resistance index and wave
      reflection decreased (- 15 +/- 4 Wood U/m(2), p < 0.001, and - 5 +/- 2 mm Hg, p <
      0.05, respectively). The breath-by-breath cardiac index correlated with the RV
      pressure waveform cardiac index estimates (r(2) = 0.95). CONCLUSIONS: RV pressure
      waveform analysis provides continuous hemodynamic assessments including cardiac
      index in acute settings. Once confirmed in long-term settings, this information
      may prove useful in optimizing a treatment regimen in patients with IPAH.

PMID- 17505046
TI  - Changes in respiratory symptoms and health-related quality of life.
AB  - BACKGROUND: For a number of chronic diseases, health-related quality of life
      (HRQoL) has become an important outcome measure. Little data are available on how
      incidence, remission, or persistence of respiratory symptoms affect HRQoL.
      METHODS: The Hordaland County Cohort Study was conducted between 1985 and 1997,
      and comprised 3,786 subjects, randomly selected, and aged 15 to 70 years in 1985.
      Respiratory symptoms were assessed both in 1985 and 1996/1997, and HRQoL was
      measured by the Short-Form 12 questionnaire in 1996/1997. Robust linear
      regression analysis was used to examine the relationship between changes in six
      respiratory symptoms and the physical component score (PCS) and mental component
      score (MCS). RESULTS: Among subjects with incidence or persistence of any of the
      six examined respiratory symptoms, PCS and MCS were significantly lower than
      among subjects without symptoms. The PCS was more reduced than the MCS in
      symptomatic subjects; however, this trend was reduced after adjustment for the
      confounder's gender, age, educational level, body mass index, and smoking status.
      Dyspnea attacks and dyspnea grade 2 had the largest negative impact on both PCS
      and MCS. CONCLUSIONS: This is the first longitudinal population study to show the
      negative impact of incidence and persistence of respiratory symptoms on HRQoL.

PMID- 17505047
TI  - A randomized trial of a self-regulation intervention for women with asthma.
AB  - BACKGROUND: Women with asthma have greater mortality and morbidity than men in
      the United States. To date, there has been no rigorous evaluation of an
      intervention focused on the particular problems in asthma management faced by
      women. This study was a randomized clinical trial of a self-regulation, telephone
      counseling intervention emphasizing women's concerns, and sex and gender role
      factors in their management of asthma. METHODS: A total of 808 women with
      diagnosed asthma were randomly assigned to the intervention group or a usual-care
      control group, including conventional asthma education. Interviews and medical
      record data were collected to assess psychosocial factors, and the behavioral
      factors of functioning, quality of life, symptoms, and health-care use at
      baseline and the subsequent 1 year. Generalized estimating equations, identity
      link, logit link, and log link were employed to analyze the data. RESULTS:
      Compared to control subjects, the women receiving treatment had greater annual
      reductions in the average number of nights with asthma symptoms (p = 0.04), days
      of missed work/school (p = 0.03), emergency department visits (p = 0.04),
      unscheduled office visits (p = 0.01), and scheduled office visits (p = 0.04).
      They had greater recognition of asthma symptoms during the menstrual cycle (p =
      0.0003), had decreased asthma symptoms with sexual activity (p = 0.008), and had
      greater improvement in quality of life (p = 0.0005), self-regulation (p = 0.03),
      and self-confidence to manage asthma (p = 0.001). CONCLUSION: The intervention
      improved women's clinical status, functioning, quality of life, and health-care
      use. A program with a focus on asthma management problems particular to women can
      significantly assist female asthma patients.

PMID- 17505048
TI  - Occupational asthma and work-exacerbated asthma: factors associated with time to
      diagnostic steps.
AB  - BACKGROUND: Little is known regarding the factors associated with the times for
      patients' first physician visit, the first physician suspicion of work-related
      asthma (WRA), and final diagnosis after the onset of WRA symptoms. This study
      examined individual and work-related factors that are associated with longer
      times to these diagnostic milestones among groups with occupational asthma (OA)
      and work-exacerbated asthma (WEA). METHOD: Suspected WRA cases were identified
      from an occupational lung disease clinic and claimants to the Ontario Workplace
      Safety and Insurance Board (100 patients each). Questionnaire administration and
      chart review were undertaken. RESULTS: Eighty participants were classified as
      having sensitizer-induced OA and 87 as having WEA. For the OA group, the risk
      factors for delay included male sex, being unmarried, low education, and lack of
      awareness of association of symptoms with work. Other factors included older age,
      being the sole income earner, and lack of knowledge of the Workplace Hazardous
      Materials Information System program. For WEA, lower household income, lower
      education, absence of a health-and-safety program at work, absence of a union,
      and lack of awareness of OA and of agents at work that could affect asthma
      significantly increased the time to diagnostic milestones. CONCLUSIONS: Different
      factors affect the diagnostic milestones for OA and WEA. Findings suggest a need
      for educational programs for workers who are at risk of OA and WEA and a need for
      further primary care physician education on WRA.

PMID- 17505050
TI  - Programming of intermediate metabolism in young lambs affected by late
      gestational maternal undernourishment.
AB  - Effects of moderate maternal undernourishment during late gestation on the
      intermediary metabolism and maturational changes in young lambs were
      investigated. 20 twin-bearing sheep, bred to two different rams, were randomly
      allocated the last 6 wk of gestation to either a NORM diet [barley, protein
      supplement, and silage ad libitum approximately 15 MJ metabolizable energy
      (ME)/day] or a LOW diet (50% of ME intake in NORM, offered exclusively as silage
      approximately 7 MJ ME/day). Post partum, ewes were fed to requirement. After
      weaning, lambs were fed concentrate and hay ad libitum. At 10 and 19 wk of age,
      lambs were subjected to an intravenous glucose tolerance test (IGTT) followed by
      24 h of fasting. Heat energy (HE) was determined in a respiration chamber at 9 or
      20 wk of age. LOW lambs had a lower birth weight and continued to be lighter
      throughout the experiment. Glucose tolerance did not differ between groups.
      However, 19-wk-old LOW lambs secreted less insulin during IGTT, released more
      NEFA, and tended to have lower leptin during fasting than NORM. Surprisingly,
      several metabolite and hormone responses during IGTT and fasting were greatly
      influenced by the paternal heritage. In conclusion, when lambs entered
      adolescence (19 wk) programming effects of late prenatal malnutrition on the
      glucose-insulin homeostasis and metabolism were manifested: LOW lambs had less
      insulin-secretory capacity, but this was apparently compensated for by increased
      target tissue sensitivity for insulin, and adipose lipolytic capacity increased
      during fasting. Thereby, glucose may be spared through increased lipid oxidation,
      but overall energetic efficiency is apparently deteriorated rather than improved.

PMID- 17505051
TI  - Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves
      control of eating in obese subjects: a 6-wk translational research study.
AB  - Evidence from rodent studies indicates that the beta-cell-derived neurohormone
      amylin exerts multiple effects on eating behavior, including reductions in meal
      size, intake of highly palatable foods, and stress-induced sucrose consumption.
      To assess the effect of amylin agonism on human eating behavior we conducted a
      randomized, blinded, placebo-controlled, multicenter study investigating the
      effects of the amylin analog pramlintide on body weight, 24-h caloric intake,
      portion sizes, "fast food" intake, and perceived control of eating in 88 obese
      subjects. After a 2-day placebo lead-in, subjects self-administered pramlintide
      (180 microg) or placebo by subcutaneous injection 15 min before meals for 6 wk
      without concomitant lifestyle modifications. Compared with placebo, pramlintide
      treatment elicited significant mean reductions from baseline in body weight on
      day 44 (-2.1 +/- 0.3 vs. +0.1 +/- 0.4%, P < 0.001), 24-h caloric intake (-990 +/-
      94 vs. -243 +/- 126 kcal on day 3, P < 0.0001; -680 +/- 86 vs. -191 +/- 161 kcal
      on day 43, P < 0.01), portion sizes, and caloric intake at a "fast food
      challenge" (-385 +/- 61 vs. -109 +/- 88 kcal on day 44, P < 0.05). Pramlintide
      treatment also improved perceived control of eating, as demonstrated by a 45%
      placebo-corrected reduction in binge eating scores (P < 0.01). The results of
      this translational research study confirm in humans various preclinical effects
      of amylin agonism, demonstrating that pramlintide-mediated weight loss in obese
      subjects is accompanied by sustained reductions in 24-h food intake, portion
      sizes, fast food intake, and binge eating tendencies.

PMID- 17505052
TI  - Regulation of muscle protein synthesis during sepsis and inflammation.
AB  - Prolonged sepsis and exposure to an inflammatory milieu decreases muscle protein
      synthesis and reduces muscle mass. As a result of its ability to integrate
      diverse signals, including hormones and nutrients, the mammalian target of
      rapamycin (mTOR) is a dominant regulator in the translational control of protein
      synthesis. Under postabsorptive conditions, sepsis decreases mTOR kinase activity
      in muscle, as evidenced by reduced phosphorylation of both eukaryotic initiation
      factor (eIF)4E-binding protein (BP)-1 and ribosomal S6 kinase (S6K)1. These
      sepsis-induced changes, along with the redistribution of eIF4E from the active
      eIF4E.eIF4G complex to the inactive eIF4E.4E-BP1 complex, are preventable by
      neutralization of tumor necrosis factor (TNF)-alpha but not by antagonizing
      glucocorticoid action. Although the ability of mTOR to respond to insulin-like
      growth factor (IGF)-I is not disrupted by sepsis, the ability of leucine to
      increase 4E-BP1 and S6K1 phosphorylation is greatly attenuated. This "leucine
      resistance" results from a cooperative interaction between both TNF-alpha and
      glucocorticoids. Finally, although septic animals are not IGF-I resistant, the
      anabolic actions of IGF-I are nonetheless reduced because of the development of
      growth hormone resistance, which decreases both circulating and muscle IGF-I.
      Herein, we highlight recent advances in the mTOR signaling network and emphasize
      their connection to the atrophic response observed in skeletal muscle during
      sepsis. Although many unanswered questions remain, understanding the cellular
      basis of the sepsis-induced decrease in translational activity will contribute to
      the rational development of therapeutic interventions and thereby minimize the
      debilitating affects of the atrophic response that impairs patient recovery.

PMID- 17505053
TI  - Effect of sleep apnea syndrome on the circadian profile of cortisol in obese men.
AB  - It has been hypothesized that sleep apnea syndrome (SAS) increases hypothalamic
      pituitary-adrenal axis activity and, through increased cortisol levels,
      participates in the pathophysiology of metabolic and cardiovascular
      complications. We compared the circadian profiles of cortisol in obese men with
      [obSAS+; apnea-hypopnea index (AHI) >or= 20/h] and without SAS (obSAS-; AHI <or=
      5/h). 1) Salivary cortisol (5 samples: before/30 min after dinner, 2100, upon/30
      min after awakening) was measured in 15 obSAS+, 19 obSAS-, and 19 normal-weight
      controls (NWC). 2) Plasma cortisol (every 30 min for 24 h under highly controlled
      conditions and portable EEG device) was measured in 9 obSAS+, 8 obSAS-, and 10
      NWC men. Visceral adipose tissue surface was measured by CT scan. In both
      studies, obSAS+ and obSAS- men were comparable for age, BMI, waist circumference,
      and waist-to-hip ratio. First, no difference was found, using ANOVA for repeated
      measures, between obSAS+ and obSAS- subjects for any salivary cortisol
      measurement. No correlation was found between salivary cortisol and AHI or
      nocturnal SaO(2). Similarly, obSAS+ and obSAS- men showed no difference in plasma
      cortisol rhythmicity: 24-h minimum, maximum, and mean, ANOVA for repeated
      measures, mathematical modeling of cortisol rhythm (COSINOR), and morning
      secretory peak. Conversely, ANOVA for repeated measures showed decreased cortisol
      levels in obese vs. NWC men during both the trough (2200-0130) and the peak (0600
      0900) independently of SAS status. We show that SAS per se is not associated with
      any change of the level or of the features of salivary and plasma cortisol
      rhythmicity and confirm that men with visceral obesity display lower plasma
      cortisol levels than NWC men.

PMID- 17505054
TI  - Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in
      islets.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone
      that has a potent stimulatory effect on insulin release under conditions of
      normal glucose tolerance. However, its insulinotropic effect is reduced or even
      absent entirely in type 2 diabetic patients. In this study, we addressed the role
      of glucose concentration in the diabetic range of >or=11 mM, i.e., hyperglycemia
      per se, as a cause of the lack of response to GIP. Culturing rat and human
      pancreatic islets in >or=11 mM glucose for up to 24 h resulted in prevention of
      GIP-mediated intracellular cAMP increase compared with culturing in 5 mM glucose.
      Western blot analysis revealed a selective 67 +/- 2% (rat) and 60 +/- 8% (human)
      decrease of GIP-R expression in islets exposed to >or=11 mM glucose compared with
      5 mM glucose (P < 0.001). We further immunoprecipitated GIP-R from islets and
      found that GIP-R was targeted for ubiquitination in a glucose- and time-dependent
      manner. Downregulation of GIP-R was rescued by treating isolated islets with
      proteasomal inhibitors lactacystin and MG-132, and the islets were once again
      capable of increasing intracellular cAMP levels in response to GIP. These results
      suggest that the GIP-R is ubiquitated, resulting in downregulation of the actions
      of GIP.

PMID- 17505055
TI  - D-Lactic acid-induced neurotoxicity in a calf model.
AB  - Lactic acidosis (DAC) occurs as a complication of short-bowel syndrome in humans
      and in a variety of other gastrointestinal disorders in monogastrics and
      ruminants. DAC is associated with signs of impaired central nervous system (CNS)
      function including ataxia and coma. The objective of this experiment was to
      determine whether either acidification of nervous tissue or d-lactic acid is
      responsible for decreased neurological function. Eight Holstein calves (32 +/- 11
      days, 70 +/- 10 kg) were surgically catheterized with indwelling intravenous
      jugular and atlanto-occipital space cerebrospinal fluid (CSF) catheters and
      infused for 6 h in random order with isomolar dl-lactic acid (dl-LA), l-lactic
      acid (l-LA), hydrochloric acid (HCl), or saline. dl-LA induced ataxia after 4 h
      of infusion and produced the greatest obtunding of CNS function (at 7 h, score
      8.0 +/- 0.4), whereas the other infusions caused neither ataxia nor scores over
      1.5 (P < 0.01 from dl-LA). dl-LA induced significantly less acidemia than HCl (at
      6 h pH 7.13 +/- 0.06 and 7.00 +/- 0.04, base excess -16 +/- 1 and -23 +/- 3
      mmol/l, bicarbonate 11 +/- 1 and 8 +/- 1 mmol/l respectively, all P < 0.01) but
      greater than l-LA and saline (P < 0.01). CSF changes followed a similar but less
      pronounced pattern. Although HCl infusion produced a severe acidemia and CSF
      acidosis, only minor effects on neurological function were evident suggesting
      that d-lactate has a direct neurotoxic effect that is independent of acidosis.
      Conversely, l-LA produced only minor neurological changes.

PMID- 17505056
TI  - Differential inhibition of CYP17A1 and CYP21A2 activities by the P450
      oxidoreductase mutant A287P.
AB  - P450 oxidoreductase (POR) has a pivotal role in facilitating electron transfer
      from nicotinamide adenine dinucleotide phosphate to microsomal cytochrome P450
      (CYP) enzymes, including the steroidogenic enzymes CYP17A1 and CYP21A2. Mutations
      in POR have been shown recently to cause congenital adrenal hyperplasia with
      apparent combined CYP17A1 and CYP21A2 deficiency that comprises a variable
      clinical phenotype, including glucocorticoid deficiency, ambiguous genitalia, and
      craniofacial malformations. To dissect structure-function relationships
      potentially explaining this phenotypic diversity, we investigated whether
      specific POR mutations have differential effects on CYP17A1 and CYP21A2. We
      compared the impact of missense mutations encoding for single amino acid changes
      in three distinct regions of the POR molecule: 1), Y181D and H628P close to the
      central electron transfer area, 2) S244C located within the hinge close to the
      flavin adenine dinucleotide and flavin mononucleotide domains of POR, and 3)
      A287P that is clearly distant from the two other regions. Functional analysis
      using a yeast microsomal assay with coexpression of human CYP17A1 or CYP21A2 with
      wild-type or mutant human POR revealed equivalent decreases in CYP17A1 and
      CYP21A2 activities by Y181D, H628P, and S244C. In contrast, A287P had a
      differential inhibitory effect, with decreased catalytic efficiency (Vmax/Km) for
      CYP17A1, whereas CYP21A2 retained near normal activity. In vivo analysis of
      urinary steroid excretion by gas chromatography/mass spectrometry in 11 patients
      with POR mutations showed that A287P homozygous patients had the highest
      corticosterone/cortisol metabolite ratios, further indicative of preferential
      inhibition of CYP17A1. These findings provide novel mechanistic insights into the
      redox regulation of human steroidogenesis. Differential interaction of POR with
      electron-accepting CYP enzymes may explain the phenotypic variability in POR
      deficiency, with additional implications for hepatic drug metabolism by POR
      dependant CYP enzymes.

PMID- 17505057
TI  - Mapping the architecture of secretin receptors with intramolecular fluorescence
      resonance energy transfer using acousto-optic tunable filter-based spectral
      imaging.
AB  - The molecular structure and agonist-induced conformational changes of class II G
      protein-coupled receptors are poorly understood. In this work, we developed and
      characterized a series of dual cyan fluorescent protein (CFP)-tagged and yellow
      fluorescent protein (YFP)-tagged secretin receptor constructs for use in various
      functional and fluorescence analyses of receptor structural variants. CFP
      insertions within the first or second intracellular loop domains of this receptor
      were tolerated poorly or partially, respectively, in receptors tagged with a
      carboxyl-terminal yellow fluorescent protein that itself had no effect on
      secretin binding or cAMP production. A similar CFP insertion into the third
      intracellular loop resulted in a plasma membrane-localized receptor that bound
      secretin and signaled normally. This fully active third-loop variant exhibited a
      significant decrease in fluorescence resonance energy transfer signals that were
      recorded with an acousto-optic tunable filter microscope after exposure to
      secretin agonist but not to a receptor antagonist. These data demonstrate changes
      in the relative positions of intracellular structures that support a model for
      secretin receptor activation.

PMID- 17505058
TI  - Estrogen induces expression of BCAS3, a novel estrogen receptor-alpha
      coactivator, through proline-, glutamic acid-, and leucine-rich protein-1
      (PELP1).
AB  - We recently reported that the breast carcinoma amplified sequence-3 (BCAS3) gene
      is regulated by estrogen receptor (ER) alpha. However, the role of ERalpha
      coactivators in the regulation of BCAS3 expression remains unknown, and
      information regarding the function of the BCAS3 protein is lacking. Here, we
      define the contribution of ERalpha coactivators to BCAS3 regulation and identify
      BCAS3 itself as an ERalpha coactivator in breast cancer cells. We found that
      PELP1 (proline-, glutamic acid-, and leucine-rich protein-1), a newly described
      ERalpha coregulator, is recruited to BCAS3 chromatin and activates its
      expression. Analysis of the BCAS3 sequence for functional motifs and evidence
      from biochemical fractionation suggested that BCAS3 acts as a transcriptional
      coactivator. Results from chromatin immunoprecipitation, reporter assays, and
      expression studies further validated the coactivator function of BCAS3 for
      ERalpha. BCAS3 physically associated with histone H3 and histone
      acetyltransferase complex protein P/CAF (p300/CBP-associated factor) and
      possessed histone acetyltransferase activity. Unexpectedly, BCAS3 required PELP1
      to function as a coactivator in ERalpha transactivation activity. In brief, these
      results highlight a mechanism whereby ERalpha activation triggers a positive
      feedback loop leading to signal amplification in the cell.

PMID- 17505059
TI  - Genomic checkpoints for exon 10 usage in the luteinizing hormone receptor type 1
      and type 2.
AB  - Alternative splicing is a hallmark of glycoprotein hormone receptor gene
      regulation, but its molecular mechanism is unknown. The LH receptor (LHR) gene
      possesses 11 exons, but exon 10 is constitutively skipped in the New World monkey
      lineage (LHR type 2), whereas it is constitutively spliced in the human (LHR type
      1). This study identifies the regulatory elements of exon 10 usage. Sequencing of
      genomic marmoset DNA revealed that the cryptic LHR exon 10 is highly homologous
      to exon 10 from other species and displays intact splice sites. Functional
      studies using a minigene approach excluded the contribution of intronic, marmoset
      specific long interspersed nucleotide-1 elements to exon 10 skipping. Sequencing
      of the genomic regions surrounding exon 10 from several primate lineages,
      sequence comparisons including the human and mouse LHR gene, revealed the
      presence of unique nucleotides at 3'-intronic position -19 and -10 and at
      position +26 within exon 10 of the marmoset LHR. Exon trap experiments and in
      vitro mutagenesis of these nucleotides resulted in the identification of a
      composite regulatory element of splicing consisting of cis-acting elements
      represented by two polypyrimidine tracts and a trans-acting element within exon
      10, which affect the secondary RNA structure. Changes within this complex
      resulted either in constitutive exon inclusion, constitutive skipping, or
      alternative splicing of exon 10. This work delineates the molecular pathway
      leading to intronization of exon 10 in the LHR type 2 and reveals, for the first
      time, the essential function of regulatory and structural elements involved in
      glycoprotein hormone receptor splicing.

PMID- 17505060
TI  - ETV1 is a novel androgen receptor-regulated gene that mediates prostate cancer
      cell invasion.
AB  - Androgens and the androgen receptor (AR) act in cells by modulating gene
      expression. Through gene microarray studies, we have identified Ets Variant Gene
      1 (ETV1) as a novel androgen-regulated gene. Our data demonstrate that ETV1 mRNA
      and protein are up-regulated in response to ligand-activated AR in androgen
      dependent LNCaP cells, but there is no detectable ETV1 expression in normal
      prostate cells. The ETV1 promoter is induced by androgens and recruits the AR in
      the context of chromatin. ETV1-regulated endogenous matrix metalloproteinase
      genes can be induced by ligand-activated AR. In contrast to the hormone-induced
      expression in androgen-dependent LNCaP cells, ETV1 expression in androgen
      independent LNCaP cells is high and unresponsive to androgen. This androgen
      independent ETV1 expression contrasts with the hormone-dependent expression
      observed for TMPRSS2 in these androgen-independent prostate cancer cells. ETV1 is
      overexpressed in prostate cancer independent of the TMPRSS2:ETV1 translocation.
      Disruption of ETV1 expression in both androgen-dependent and androgen-independent
      prostate cancer cells significantly compromises the invasion capacity of these
      cells, suggesting an important role for ETV1 in prostate cancer metastasis.
      Collectively, these results demonstrate that ETV1 expression transitions from
      androgen-induced to androgen-independent as prostate cancer cells switch from
      hormone-dependent to hormone-refractory and suggest that this transition may be
      in part responsible for the elevated levels of ETV1 observed in prostate tumors.
      Additionally, our data provide an indirect mechanism of AR regulation of gene
      expression, via the transactivation of the transcription factor ETV1.

PMID- 17505061
TI  - Sirtuin 1 is required for antagonist-induced transcriptional repression of
      androgen-responsive genes by the androgen receptor.
AB  - Androgen antagonists or androgen deprivation is a primary therapeutic modality
      for the treatment of prostate cancer. Invariably, however, the disease becomes
      progressive and unresponsive to androgen ablation therapy (hormone refractory).
      The molecular mechanisms by which the androgen antagonists inhibit prostate
      cancer proliferation are not fully defined. In this report, we demonstrate that
      sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide-dependent histone
      deacetylase (HDAC) linked to the regulation of longevity, is required for
      androgen antagonist-mediated transcriptional repression and growth suppression.
      Androgen antagonist-bound androgen receptor (AR) recruits SIRT1 and nuclear
      receptor corepressor to AR-responsive promoters and deacetylates histone H3
      locally at the prostate-specific antigen promoter. Furthermore, SIRT1 down
      regulation by small interfering RNA or by pharmacological means increased the
      sensitivity of androgen-responsive genes to androgen stimulation, enhanced the
      sensitivity of prostate cancer cell proliferative responses to androgens, and
      decreased the sensitivity of prostate cancer cells to androgen antagonists. In
      this study, we demonstrate the ligand-dependent recruitment of a class III HDAC
      into a corepressor transcriptional complex and a necessary functional role for a
      class III HDAC as a transcriptional corepressor in AR antagonist-induced
      transcriptional repression. Collectively, these findings identify SIRT1 as a
      corepressor of AR and elucidate a new molecular pathway relevant to prostate
      cancer growth and approaches to therapy.

PMID- 17505062
TI  - Growth factor signaling pathways modulate BRCA1 repression of estrogen receptor
      alpha activity.
AB  - The breast cancer susceptibility gene BRCA1 is mutated in about one half of all
      hereditary breast cancer cases, and its expression is frequently decreased in
      sporadic cancers. Previously, we demonstrated a functional interaction between
      the BRCA1 and estrogen receptor-alpha (ER-alpha) proteins that causes inhibition
      of ER-alpha signaling. Here, we examined the role of growth factor signaling
      pathways in modulating this interaction. We found that underexpression of BRCA1
      caused ligand-independent activation of ER-alpha that was mediated through
      phosphatidylinositol-3 kinase (PI3K)/c-Akt signaling. BRCA1 underexpression also
      enhanced estrogen-inducible ER-alpha activity in a PI3K/Akt-dependent manner.
      Exogenous c-Akt conferred estrogen-independent ER-alpha activation and rescued
      the BRCA1 repression of estrogen-stimulated ER-alpha activity. BRCA1 knockdown
      stimulated c-Akt activity, in part, by inhibiting the activity of protein
      phosphatase 2A, an enzyme that dephosphorylates Akt. ERs with point mutations of
      several growth factor-targeted serine residues (S167A, S118A, and S118/167A) were
      resistant to repression by BRCA1, although the single point mutant receptors
      still associated with the BRCA1 protein. The enhanced ER-alpha activity
      attributable to BRCA1 knockdown was dependent, in part, on serine residues 167
      and 118 of ER-alpha. BRCA1 knockdown caused an increase in ER-alpha
      phosphorylation on serine-167 (but not serine-118 or serine-104/106) that was
      dependent on PI3K/Akt signaling and was mimicked by pharmacologic inhibition of
      protein phosphatase 2A. These findings suggest that BRCA1 regulates Akt signaling
      and the PI3K/Akt pathway modulates the ability of BRCA1 to repress ER-alpha, in
      part through serine phosphorylation events in the activation function-1 domain of
      ER-alpha.

PMID- 17505064
TI  - Surviving antioxidant supplements.

PMID- 17505063
TI  - The HER4 cytoplasmic domain, but not its C terminus, inhibits mammary cell
      proliferation.
AB  - Unlike the proliferative action of other epidermal growth factor (EGF) receptor
      family members, HER4/ErbB4 is often associated with growth-inhibitory and
      differentiation signaling. These actions may involve HER4 two-step proteolytic
      processing by intramembraneous gamma-secretase, releasing the soluble,
      intracellular 80-kDa HER4 cytoplasmic domain, s80HER4. We demonstrate that
      pharmacological inhibition of either gamma-secretase activity or HER4 tyrosine
      kinase activity blocked heregulin-dependent growth inhibition of SUM44 breast
      cancer cells. We next generated breast cell lines stably expressing GFP-s80HER4
      [green fluorescent protein (GFP) fused to the N terminus of the HER4 cytoplasmic
      domain, residues 676-1308], GFP-CT(HER4) (GFP fused to N terminus of the HER4 C
      terminus distal to the tyrosine kinase domain, residues 989-1308), or GFP alone.
      Both GFP-s80HER4 and GFP-CTHER4 were found in the nucleus, but GFP-s80HER4
      accumulated to a greater extent and sustained its nuclear localization. s80HER4
      was constitutively tyrosine phosphorylated, and treatment of cells with a
      specific HER family tyrosine kinase inhibitor 1) blocked tyrosine
      phosphorylation; 2) markedly diminished GFP-s80HER4 nuclear localization; and 3)
      reduced signal transducer and activator of transcription (STAT)5A tyrosine
      phosphorylation and nuclear localization as well as GFP-s80HER4:STAT5A
      interaction. Multiple normal mammary and breast cancer cell lines, stably
      expressing GFP-s80HER4 (SUM44, MDA-MB-453, MCF10A, SUM102, and HC11) were growth
      inhibited compared with the same cell line expressing GFP-CTHER4 or GFP alone.
      The s80HER4-induced cell number reduction was due to slower growth because rates
      of apoptosis were equivalent in GFP-, GFP-CTHER4-, and GFP-s80HER4-expressing
      cells. Lastly, GFP-s80HER4 enhanced differentiation signaling as indicated by
      increased basal and prolactin-dependent beta-casein expression. These results
      indicate that surface HER4 tyrosine phosphorylation and ligand-dependent release
      of s80HER4 are necessary, and s80HER4 signaling is sufficient for HER4-dependent
      growth inhibition.

PMID- 17505065
TI  - The if's, and's, or but's regarding bisphosphonates for prostate cancer.

PMID- 17505066
TI  - Amid health concerns, FDA reviews safety of several heavily used anemia drugs.

PMID- 17505067
TI  - Proposed FDA conflict-of-interest guidelines get lukewarm reception.

PMID- 17505068
TI  - Can reducing nicotine help wean smokers?

PMID- 17505069
TI  - Debate over sentinel node biopsy continues.

PMID- 17505070
TI  - Stat bite: Japan's cancer death rate.

PMID- 17505071
TI  - Multivitamin use and risk of prostate cancer in the National Institutes of Health
      AARP Diet and Health Study.
AB  - BACKGROUND: Multivitamin supplements are used by millions of Americans because of
      their potential health benefits, but the relationship between multivitamin use
      and prostate cancer is unclear. METHODS: We prospectively investigated the
      association between multivitamin use and risk of prostate cancer (localized,
      advanced, and fatal) in 295,344 men enrolled in the National Institutes of Health
      (NIH)-AARP Diet and Health Study who were cancer free at enrollment in 1995 and
      1996. During 5 years of follow-up, 10,241 participants were diagnosed with
      incident prostate cancer, including 8765 localized and 1476 advanced cancers. In
      a separate mortality analysis with 6 years of follow-up, 179 cases of fatal
      prostate cancer were ascertained. Multivitamin use was assessed at baseline as
      part of a self-administered, mailed food-frequency questionnaire. Relative risks
      (RRs) and 95% confidence intervals (CIs) were calculated by use of Cox
      proportional hazards regression, adjusted for established or suspected prostate
      cancer risk factors. RESULTS: No association was observed between multivitamin
      use and risk of localized prostate cancer. However, we found an increased risk of
      advanced and fatal prostate cancers (RR = 1.32, 95% CI = 1.04 to 1.67 and RR =
      1.98, 95% CI = 1.07 to 3.66, respectively) among men reporting excessive use of
      multivitamins (more than seven times per week) when compared with never users.
      The incidence rates per 100,000 person-years for advanced and fatal prostate
      cancers for those who took a multivitamin more than seven times per week were
      143.8 and 18.9, respectively, compared with 113.4 and 11.4 in never users. The
      positive associations with excessive multivitamin use were strongest in men with
      a family history of prostate cancer or who took individual micronutrient
      supplements, including selenium, beta-carotene, or zinc. CONCLUSION: These
      results suggest that regular multivitamin use is not associated with the risk of
      early or localized prostate cancer. The possibility that men taking high levels
      of multivitamins along with other supplements have increased risk of advanced and
      fatal prostate cancers is of concern and merits further evaluation.

PMID- 17505072
TI  - Oral sodium clodronate for nonmetastatic prostate cancer--results of a randomized
      double-blind placebo-controlled trial: Medical Research Council PR04
      (ISRCTN61384873).
AB  - BACKGROUND: The most frequent site of metastases from prostate cancer is bone.
      Adjuvant bisphosphonate treatment improves outcomes of patients with bone
      metastasis-negative breast cancer, but the effects of bisphosphonates on bone
      metastases in prostate cancer are not known. METHODS: We performed a randomized
      double-blind placebo-controlled trial to determine whether a first-generation
      bisphosphonate could improve symptomatic bone metastasis-free survival (time to
      symptomatic bone metastases or death from prostate cancer) in men with
      nonmetastatic prostate cancer who were at high risk of developing bone
      metastases. Between June 1, 1994, and December 31, 1997, 508 men from 26 UK sites
      and one New Zealand site who were within 3 years of initial prostate cancer
      diagnosis with no evidence of metastases from current bone scanning were randomly
      assigned to daily oral sodium clodronate (2080 mg/day, n = 254) or placebo (n =
      254) for a maximum of 5 years. Estimates of outcome risks were compared using
      Kaplan-Meier analyses. RESULTS: The groups allocated to each treatment were well
      balanced. After a median follow-up of nearly 10 years, no evidence of benefit to
      the clodronate group was observed in terms of bone metastases-free survival
      (clodronate versus placebo, 80 events versus 68 events; hazard ratio [HR] = 1.22;
      95% confidence interval [CI] = 0.88 to 1.68) or overall survival (clodronate
      versus placebo, 130 deaths versus 127 deaths; HR = 1.02; 95% CI = 0.80 to 1.30).
      Adverse events, notably gastrointestinal problems and increased lactate
      dehydrogenase levels, were more frequent in the clodronate group than in the
      placebo group; otherwise, clodronate was well tolerated. Modification of trial
      drug dose was more frequent in the clodronate group than the placebo group (HR =
      1.63, 95% CI = 1.21 to 2.19). CONCLUSION: Adjuvant sodium clodronate does not
      modify the natural history of nonmetastatic prostate cancer.

PMID- 17505073
TI  - Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers,
      and the risk of head and neck cancer: pooled analysis in the International Head
      and Neck Cancer Epidemiology Consortium.
AB  - BACKGROUND: At least 75% of head and neck cancers are attributable to a
      combination of cigarette smoking and alcohol drinking. A precise understanding of
      the independent association of each of these factors in the absence of the other
      with the risk of head and neck cancer is needed to elucidate mechanisms of head
      and neck carcinogenesis and to assess the efficacy of interventions aimed at
      controlling either risk factor. METHODS: We examined the extent to which head and
      neck cancer is associated with cigarette smoking among never drinkers and with
      alcohol drinking among never users of tobacco. We pooled individual-level data
      from 15 case-control studies that included 10,244 head and neck cancer case
      subjects and 15,227 control subjects, of whom 1072 case subjects and 5775 control
      subjects were never users of tobacco and 1598 case subjects and 4051 control
      subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated using unconditional logistic regression models.
      All statistical tests were two-sided. RESULTS: Among never drinkers, cigarette
      smoking was associated with an increased risk of head and neck cancer (OR for
      ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear
      dose-response relationships for the frequency, duration, and number of pack-years
      of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck
      cancer cases among nondrinkers in this study would have been prevented if these
      individuals had not smoked cigarettes. Among never users of tobacco, alcohol
      consumption was associated with an increased risk of head and neck cancer only
      when alcohol was consumed at high frequency (OR for three or more drinks per day
      versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high
      frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and
      larynx. CONCLUSIONS: Our results represent the most precise estimates available
      of the independent association of each of the two main risk factors of head and
      neck cancer, and they exemplify the strengths of large-scale consortia in cancer
      epidemiology.

PMID- 17505074
TI  - Risk of second malignant neoplasms after childhood leukemia and lymphoma: an
      international study.
AB  - BACKGROUND: Survivors of childhood leukemia and lymphoma experience high risks of
      second malignant neoplasms. We quantified such risk using a large dataset from 13
      population-based cancer registries. METHODS: The registries provided individual
      data on cases of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma occurring
      in children aged 0-14 years and on subsequent second malignant neoplasms for
      different time periods from 1943 to 2000. Risks of second malignant neoplasms
      were assessed through standardized incidence ratios (SIRs) and corresponding 95%
      confidence intervals (CIs), using the incidence rates in the general populations
      covered by the registries as a reference. Cumulative absolute risks were also
      calculated. RESULTS: A total of 133 second malignant neoplasms were observed in
      16,540 patients (12,731 leukemias, 1246 Hodgkin lymphomas, and 2563 non-Hodgkin
      lymphomas) after an average follow-up of 6.5 years. The most frequent second
      malignancies after leukemia were brain cancer (19 cases, SIR = 8.52, 95% CI =
      5.13 to 13.3), non-Hodgkin lymphoma (nine cases, SIR = 9.41, 95% CI = 4.30 to
      17.9), and thyroid cancer (nine cases, SIR = 18.8, 95% CI = 8.60 to 35.7); the
      most frequent after Hodgkin lymphoma were thyroid cancer (nine cases, SIR = 52.5,
      95% CI = 24.0 to 99.6), breast cancer (six cases, SIR = 20.9, 95% CI = 7.66 to
      45.4), and neoplasms of skin (non-melanoma) (six cases, SIR = 34.0, 95% CI = 12.5
      to 74.0); and the most frequent after non-Hodgkin lymphoma were thyroid cancer
      (six cases, SIR = 40.4, 95% CI = 14.8 to 88.0) and brain cancer (four cases, SIR
      = 6.97, 95% CI = 1.90 to 17.9). Cumulative incidence of any second malignant
      neoplasm was 2.43% (95% CI = 1.09 to 3.78), 12.7% (95% CI = 8.29 to 17.2), and
      2.50% (95% CI = 1.04 to 3.96) within 30 years from diagnosis of leukemia, Hodgkin
      lymphoma, and non-Hodgkin lymphoma, respectively. CONCLUSIONS: This population
      based study provides, to our knowledge, the most precise and up-to-date estimates
      for relative and absolute risks of second malignant neoplasms after childhood
      leukemia and lymphoma.

PMID- 17505075
TI  - Alcohol intake and renal cell cancer in a pooled analysis of 12 prospective
      studies.
AB  - BACKGROUND: The association between alcohol intake and risk of renal cell cancer
      has been inconsistent in case-control studies. An inverse association between
      alcohol intake and risk of renal cell cancer has been suggested in a few
      prospective studies, but each of these studies included a small number of cases.
      METHODS: We performed a pooled analysis of 12 prospective studies that included
      530,469 women and 229,575 men with maximum follow-up times of 7-20 years. All
      participants had completed a validated food-frequency questionnaire at baseline.
      Using the primary data from each study, the study-specific relative risks (RRs)
      for renal cell cancer were calculated using Cox proportional hazards models and
      then pooled using a random-effects model. All statistical tests were two-sided.
      RESULTS: A total of 1430 (711 women and 719 men) cases of incident renal cell
      cancer were identified. The study-standardized incidence rates of renal cell
      cancer were 23 per 100,000 person-years among nondrinkers and 15 per 100,000
      person-years among those who drank 15 g/day or more of alcohol. Compared with
      nondrinking, alcohol consumption (> or = 15 g/day, equivalent to slightly more
      than one alcoholic drink per day) was associated with a decreased risk of renal
      cell cancer (pooled multivariable RR = 0.72, 95% confidence interval = 0.60 to
      0.86; P(trend)<.001); statistically significant inverse trends with increasing
      intake were seen in both women and men. No difference by sex was observed
      (P(heterogeneity) = .89). Associations between alcohol intake and renal cell
      cancer were not statistically different across alcoholic beverage type (beer
      versus wine versus liquor) (P = .40). CONCLUSION: Moderate alcohol consumption
      was associated with a lower risk of renal cell cancer among both women and men in
      this pooled analysis.

PMID- 17505076
TI  - Critical role for Fas-associated death domain-like interleukin-1-converting
      enzyme-like inhibitory protein in anoikis resistance and distant tumor formation.
AB  - BACKGROUND: Normal epithelial cells undergo anoikis, or apoptosis on loss of
      anchorage to the extracellular matrix, by initiating the death receptor pathway
      of caspase activation. However, malignant epithelial cells with metastatic
      potential resist anoikis and can survive in an anchorage-independent fashion. We
      hypothesized that c-Fas-associated death domain-like interleukin-1-converting
      enzyme-like inhibitory protein (FLIP), an endogenous inhibitor of death receptor
      signaling, may suppress anoikis. METHODS: We assessed viability and apoptosis of
      PPC-1 prostate cancer cells cultured in adherent and suspension conditions using
      3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium inner salt and Annexin V staining assays. Expression of the death
      receptor Fas and activation of caspase 8 were measured using flow cytometry.
      Expression of Fas ligand was measured by reverse transcription-polymerase chain
      reaction. FLIP protein expression was measured by immunoblotting. Small-molecule
      inhibitors of FLIP (including the death receptor sensitizer 5809354) and small
      interfering (si) RNA directed against FLIP were used to assess the effects of
      FLIP inhibition on anoikis of prostate cancer cells in vitro and in vivo. All
      statistical tests were two-sided. RESULTS: PPC-1 cells cultured in suspension
      resisted anoikis, despite increased expression of Fas (0 versus 8 hours, mean
      relative percent expression = 100% versus 135%, difference = 35%, 95% confidence
      interval [CI] = 10% to 61%; P = .02) and Fas L (0 versus 24 hours, mean relative
      percent expression = 100% versus 208%, difference = 108%, 95% CI = 18% to 197%; P
      = .02). Knockdown of FLIP expression by siRNA or treatment with 5809354
      sensitized prostate cancer cells to anoikis (control siRNA versus FLIP siRNA at
      10 nM, mean relative percent viability = 95% versus 51%, difference = 44%, 95% CI
      = 34% to 54%; P<.001; control versus 5809354 at 20 microM, mean relative percent
      viability = 96% versus 52%, difference = 44%, 95% CI = 13% to 75%; P = .015).
      Inhibition of FLIP expression specifically activated caspase 8 in PPC-1 cells
      grown in suspension but not adherent conditions and decreased the metastatic
      potential of circulating PPC-1 cells in vivo. CONCLUSIONS: FLIP may be a
      suppressor of anoikis and therefore a possible target for antimetastatic
      therapeutic strategies.

PMID- 17505077
TI  - Extrasynaptic NMDA receptors reshape gene ranks.
AB  - The N-methyl-D-aspartate (NMDA) subtype of glutamate receptors (NMDAR) plays a
      key role in the control of neuronal plasticity and cell survival by modifying the
      activity of different signaling pathways and numerous genes. However, it remains
      unclear how the activation of this one class of glutamate receptors can lead to
      different functional consequences, such as enhancement of neuronal survival or
      induction of neuronal death. Recent work further refines the hypothesis that
      synaptic and extrasynaptic NMDARs have distinct roles in neuronal survival and
      death by showing that these two subpopulations of NMDARs differentially modify
      whole-genome activity.

PMID- 17505078
TI  - The regulation of nuclear membrane permeability by Ca2+ signaling: a tightly
      regulated pore or a floodgate?
AB  - The nuclear pore complex functions both to separate and to connect the nucleus
      and the cytoplasm. Minute-to-minute changes in gene expression depend on rapid
      translocation of transcription factors and other regulatory proteins from the
      cytosol into the nucleus. However, a controversy exists as to whether cell
      signaling allows large molecules to enter the nucleus through tightly regulated
      facilitated transport or by the opening of a floodgate. A recent report
      suggesting that some hormones increase nuclear permeability through changes in
      intracellular Ca(2+) concentration has reignited this debate. Here, I consider
      both the basic permeability of the nuclear membrane under resting conditions and
      the effects of Ca(2+) on the permeability of the nuclear pore. I discuss
      facilitated transport through the nuclear pore complex, with particular attention
      to the nuclear transport of Ca(2+)-CaM signaling complexes. Finally, I weigh the
      arguments in favor of a generic increase in permeability versus stimulation of
      facilitated transport as possible mechanisms for mediating cell signaling to the
      nucleus.

PMID- 17505079
TI  - Cardioverter-defibrillator box damage secondary to lead insulation defect.

PMID- 17505080
TI  - Fast laser scanning optical-CT apparatus for 3D radiation dosimetry.
AB  - Optical computed tomography (optical-CT) of 3D radiation dosimeters is a
      promising avenue for delivering an economic and reliable quality control of
      radiotherapy treatments such as intensity modulated radiotherapy, brachytherapy
      and stereotactic radiosurgery. The main problems in transferring 3D dosimeters to
      clinical setting have been in (1) the complexity of manufacture and behaviour of
      3D dosimeters and (2) time-consuming readout and analysis of 3D dosimeters. This
      paper addresses the readout problem by showing that fast (20 min tomography
      scan), precise (projection absorbance signal-to-noise ratio is greater than 100:1
      across the absorbance range 0.2 to 1.5) and accurate (good linearity in the
      calibration curve) measurements are possible using a novel method of optically
      scanning a laser beam across the 3D dosimeter.

PMID- 17505081
TI  - Monte Carlo simulations of the dosimetric impact of radiopaque fiducial markers
      for proton radiotherapy of the prostate.
AB  - Many clinical studies have demonstrated that implanted radiopaque fiducial
      markers improve targeting accuracy in external-beam radiotherapy, but little is
      known about the dose perturbations these markers may cause in patients receiving
      proton radiotherapy. The objective of this study was to determine what types of
      implantable markers are visible in setup radiographs and, at the same time,
      perturb the therapeutic proton dose to the prostate by less than 10%. The
      radiographic visibility of the markers was assessed by visual inspection of
      lateral setup radiographs of a pelvic phantom using a kilovoltage x-ray imaging
      system. The fiducial-induced perturbations in the proton dose were estimated with
      Monte Carlo simulations. The influence of marker material, size, placement depth
      and orientation within the pelvis was examined. The radiographic tests confirmed
      that gold and stainless steel markers were clearly visible and that titanium
      markers were not. The Monte Carlo simulations revealed that titanium and
      stainless steel markers minimally perturbed the proton beam, but gold markers
      cast unacceptably large dose shadows. A 0.9 mm diameter, 3.1 mm long cylindrical
      stainless steel marker provides good radiographic visibility yet perturbs the
      proton dose distribution in the prostate by less than 8% when using a parallel
      opposed lateral beam arrangement.

PMID- 17505082
TI  - Arrhenius temperature dependence of in vitro tissue plasminogen activator
      thrombolysis.
AB  - Stroke is a devastating disease and a leading cause of death and disability.
      Currently, the only FDA approved therapy for acute ischemic stroke is the
      intravenous administration of the thrombolytic medication, recombinant tissue
      plasminogen activator (tPA). However, this treatment has many contraindications
      and can have dangerous side effects such as intra-cerebral hemorrhage. These
      treatment limitations have led to much interest in potential adjunctive
      therapies, such as therapeutic hypothermia (T <or 35 degrees C) and ultrasound
      enhanced thrombolysis. Such interest may lead to combining these therapies with
      tPA to treat stroke, however little is known about the effects of temperature on
      the thrombolytic efficacy of tPA. In this work, we measure the temperature
      dependence of the fractional clot mass loss Deltam(T) resulting from tPA exposure
      in an in vitro human clot model. We find that the temperature dependence is well
      described by an Arrhenius temperature dependence with an effective activation
      energy E(eff) of 42.0 +/- 0.9 kJ mole(-1). E(eff) approximates the activation
      energy of the plasminogen-to-plasmin reaction of 48.9 kJ mole(-1). A model to
      explain this temperature dependence is proposed. These results will be useful in
      predicting the effects of temperature in future lytic therapies.

PMID- 17505083
TI  - Modelling the effect of laminar axially directed blood flow on the dissolution of
      non-occlusive blood clots.
AB  - Axially directed blood plasma flow can significantly accelerate thrombolysis of
      non-occlusive blood clots. Viscous forces caused by shearing of blood play an
      essential role in this process, in addition to biochemical fibrinolytic
      reactions. An analytical mathematical model based on the hypothesis that clot
      dissolution dynamics is proportional to the power of the flowing blood plasma
      dissipated along the clot is presented. The model assumes cylindrical non
      occlusive blood clots with the flow channel in the centre, in which the flow is
      assumed to be laminar and flow rate constant at all times during dissolution.
      Effects of sudden constriction on the flow and its impact on the dissolution rate
      are also considered. The model was verified experimentally by dynamic magnetic
      resonance (MR) microscopy of artificial blood clots dissolving in an in vitro
      circulation system, containing plasma with a magnetic resonance imaging contrast
      agent and recombinant tissue-type plasminogen activator (rt-PA). Sequences of
      dynamically acquired 3D low resolution MR images of entire clots and 2D high
      resolution MR images of clots in the axial cross-section were used to evaluate
      the dissolution model by fitting it to the experimental data. The experimental
      data fitted well to the model and confirmed our hypothesis.

PMID- 17505084
TI  - Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic
      optimization.
AB  - A number of patients with lung cancer receive either palliative or curative high
      dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated
      with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an
      expected potential consequence of HDR, we have calculated the radial dose
      distribution for an Ir-192 HDR source, rigorously examined the dose and
      prescription points recommended by the American Brachytherapy Society (ABS), and
      performed a radiobiological-based analysis. The radial dose rate of a
      commercially available Ir-192 source was calculated with a Monte Carlo
      simulation. Based on the linear quadratic model, the estimated palliative,
      curative and blood vessel rupture radii from the center of an Ir-192 source were
      obtained for the ABS recommendations and a series of customized HDR
      prescriptions. The estimated radius at risk for blood vessel perforation for the
      ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some
      situations reduce this radius to 4 mm. The estimated blood perforation radius is
      generally smaller than the palliative radius. Optimized and individualized
      endobronchial HDR prescriptions are currently feasible based on our current
      understanding of tumor and normal tissue radiobiology. Individualized
      prescriptions could minimize complications such as fatal hemoptysis without
      sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the
      use of CT imaging to better assess the relationship between the catheter and
      blood vessels promise to be useful strategies for increasing the therapeutic
      index of this treatment modality. Prospective trials employing treatment
      optimization algorithms are needed.

PMID- 17505085
TI  - Analysis of recoverable current from one component of magnetic flux density in
      MREIT and MRCDI.
AB  - Magnetic resonance current density imaging (MRCDI) provides a current density
      image by measuring the induced magnetic flux density within the subject with a
      magnetic resonance imaging (MRI) scanner. Magnetic resonance electrical impedance
      tomography (MREIT) has been focused on extracting some useful information of the
      current density and conductivity distribution in the subject Omega using measured
      B(z), one component of the magnetic flux density B. In this paper, we analyze the
      map Tau from current density vector field J to one component of magnetic flux
      density B(z) without any assumption on the conductivity. The map Tau provides an
      orthogonal decomposition J = J(P) + J(N) of the current J where J(N) belongs to
      the null space of the map Tau. We explicitly describe the projected current
      density J(P) from measured B(z). Based on the decomposition, we prove that B(z)
      data due to one injection current guarantee a unique determination of the
      isotropic conductivity under assumptions that the current is two-dimensional and
      the conductivity value on the surface is known. For a two-dimensional dominating
      current case, the projected current density J(P) provides a good approximation of
      the true current J without accumulating noise effects. Numerical simulations show
      that J(P) from measured B(z) is quite similar to the target J. Biological tissue
      phantom experiments compare J(P) with the reconstructed J via the reconstructed
      isotropic conductivity using the harmonic B(z) algorithm.

PMID- 17505086
TI  - Quantitative analysis of the effect of energy separation in k-edge digital
      subtraction imaging.
AB  - The aim of the work is to quantitatively compare the effect of the energy
      separation in the k-edge digital subtraction imaging technique. Images of a
      custom-made, iodine filled (k-edge = 33.17 keV) test object have been acquired
      with monochromatic x-ray beams (energy spread <0.1 keV) at the ID17 biomedical
      beamline of the ESRF. Image acquisition has been performed using two energy
      separations, namely 0.65 keV (32.85 keV and 33.5 keV, respectively) and 4.4 keV
      (31.2 keV and 35.6 keV, respectively), using beams of energies on either side of
      the iodine k-edge. Signal and signal-to-noise ratio (SNR) analysis has been
      performed as a function of DeltaE and the contrast medium concentrations. The
      results show that the SNR values measured for DeltaE < 1 keV are only slightly
      higher than those measured for DeltaE = 4.4 keV. This preliminary study shows
      that monochromaticity and the energy separation obtained with quasi monochromatic
      beams from conventional x-ray sources might be suitable for this imaging
      technique.

PMID- 17505087
TI  - Fast hybrid SPECT simulation including efficient septal penetration modelling (SP
      PSF).
AB  - Single photon emission computed tomography (SPECT) images are degraded by the
      detection of scattered photons and photons that penetrate the collimator septa.
      In this paper, a previously proposed Monte Carlo software that employs fast
      object scatter simulation using convolution-based forced detection (CFD) is
      extended towards a wide range of medium and high energy isotopes measured using
      various collimators. To this end, a fast method was developed for incorporating
      effects of septal penetrating (SP) photons. The SP contributions are obtained by
      calculating the object attenuation along the path from primary emission to
      detection followed by sampling a pre-simulated and scalable septal penetration
      point spread function (SP-PSF). We found that with only a very slight reduction
      in accuracy, we could accelerate the SP simulation by four orders of magnitude.
      To achieve this, we combined: (i) coarse sampling of the activity and attenuation
      distribution; (ii) simulation of the penetration only for a coarse grid of
      detector pixels followed by interpolation and (iii) neglection of SP-PSF elements
      below a certain threshold. By inclusion of this SP-PSF-based simulation it became
      possible to model both primary and septal penetrated photons while only 10% extra
      computation time was added to the CFD-based Monte Carlo simulator. As a result, a
      SPECT simulation of a patient-like distribution including SP now takes less than
      5 s per projection angle on a dual processor PC. Therefore, the simulator is well
      suited as an efficient projector for fully 3D model-based reconstruction or as a
      fast data-set generator for applications such as image processing optimization or
      observer studies.

PMID- 17505088
TI  - 3-Point support mechanical steering system for high intensity focused ultrasound.
AB  - We have developed a simple approach for mechanically scanning a focused bowl
      ultrasound (US) transducer for either hyperthermia or tissue ablation therapies
      called the 3-point support (3PS) mechanical steering technique. The scanning
      involves translation of the required 3D motion of the ultrasound transducer to
      the more manageable linear movement of three support rods. It is a cost-effective
      alternative, especially compared with electronic scanning and other previous
      implementations of mechanically scanned systems. The 3PS approach is particularly
      well suited for integration with our microwave breast imaging technique--the
      combination of which could be an effective, low-cost thermal therapy/monitoring
      approach. The results show that the US focus can be moved laterally in a spiral
      pattern 3 cm below the surface in a gel phantom and that similar patterns can be
      moved to multiple locations within the phantom volume in succession. The
      feasibility of simultaneously acquiring microwave thermal images is also
      demonstrated.

PMID- 17505089
TI  - Monte Carlo simulations of compact gamma cameras based on avalanche photodiodes.
AB  - Avalanche photodiodes (APDs), and in particular position-sensitive avalanche
      photodiodes (PSAPDs), are an attractive alternative to photomultiplier tubes
      (PMTs) for reading out scintillators for PET and SPECT. These solid-state devices
      offer high gain and quantum efficiency, and can potentially lead to more compact
      and robust imaging systems with improved spatial and energy resolution. In order
      to evaluate this performance improvement, we have conducted Monte Carlo
      simulations of gamma cameras based on avalanche photodiodes. Specifically, we
      investigated the relative merit of discrete and PSAPDs in a simple continuous
      crystal gamma camera. The simulated camera was composed of either a 4 x 4 array
      of four channels 8 x 8 mm2 PSAPDs or an 8 x 8 array of 4 x 4 mm2 discrete APDs.
      These configurations, requiring 64 channels readout each, were used to read the
      scintillation light from a 6 mm thick continuous CsI:Tl crystal covering the
      entire 3.6 x 3.6 cm2 photodiode array. The simulations, conducted with GEANT4,
      accounted for the optical properties of the materials, the noise characteristics
      of the photodiodes and the nonlinear charge division in PSAPDs. The performance
      of the simulated camera was evaluated in terms of spatial resolution, energy
      resolution and spatial uniformity at 99mTc (140 keV) and 125I ( approximately 30
      keV) energies. Intrinsic spatial resolutions of 1.0 and 0.9 mm were obtained for
      the APD- and PSAPD-based cameras respectively for 99mTc, and corresponding values
      of 1.2 and 1.3 mm FWHM for 125I. The simulations yielded maximal energy
      resolutions of 7% and 23% for 99mTc and 125I, respectively. PSAPDs also provided
      better spatial uniformity than APDs in the simple system studied. These results
      suggest that APDs constitute an attractive technology especially suitable to
      build compact, small field of view gamma cameras dedicated, for example, to small
      animal or organ imaging.

PMID- 17505090
TI  - Quantitative validation of the 3D SAR profile of hyperthermia applicators using
      the gamma method.
AB  - For quality assurance of hyperthermia treatment planning systems, quantitative
      validation of the electromagnetic model of an applicator is essential. The
      objective of this study was to validate a finite-difference time-domain (FDTD)
      model implementation of the Lucite cone applicator (LCA) for superficial
      hyperthermia. The validation involved (i) the assessment of the match between the
      predicted and measured 3D specific absorption rate (SAR) distribution, and (ii)
      the assessment of the ratio between model power and real-world power. The 3D SAR
      distribution of seven LCAs was scanned in a phantom bath using the DASY4
      dosimetric measurement system. The same set-up was modelled in SEMCAD X. The
      match between the predicted and the measured SAR distribution was quantified with
      the gamma method, which combines distance-to-agreement and dose difference
      criteria. Good quantitative agreement was observed: more than 95% of the
      measurement points met the acceptance criteria 2 mm/2% for all applicators. The
      ratio between measured and predicted power absorption ranged from 0.75 to 0.92
      (mean 0.85). This study shows that quantitative validation of hyperthermia
      applicator models is feasible and is worth considering as a part of hyperthermia
      quality assurance procedures.

PMID- 17505091
TI  - Development of a guarded liquid ionization chamber for clinical dosimetry.
AB  - Liquid ionization chambers are considered superior to air-filled chambers in
      terms of size, energy dependence and perturbation effects. We constructed and
      tested a liquid ionization chamber for clinical dosimetry, the GLIC-03, with a
      sensitive volume of approximately 2 mm3. We also examined two methods to correct
      for general ion recombination in pulsed photon beams: that of Johansson et al,
      which modifies Boag's theory for recombination in gases, and an empirical method
      relating recombination to dose per pulse. The second method can be used even in
      cases where the first method is not applicable. The response of the GLIC-03
      showed a stable, linear and reproducible decrease of 1% over 10 h. The liquid
      filled GLIC-03 had a 1.1 +/- 0.4% energy dependence while that of the air-filled
      GLIC-03 was 2.1 +/- 0.3% between the 6 and 18 MV beams from a Clinac 21EX. The
      two methods for recombination correction agreed within 0.2% for measurements at
      18 MV, 700 V, 100 MU min(-1). Measurements with the GLIC-03 in Solid Water in the
      build-up region of an 18 MV beam agreed with extrapolation chamber measurements
      within 1.4%, indicating that the GLIC-03 causes minimal perturbation.

PMID- 17505092
TI  - Dosimetry accuracy as a function of seed localization uncertainty in permanent
      prostate brachytherapy: increased seed number correlates with less variability in
      prostate dosimetry.
AB  - The variation of permanent prostate brachytherapy dosimetry as a function of seed
      localization uncertainty was investigated for I-125 implants with seed activities
      commonly employed in contemporary practice. Post-implant imaging and radiation
      dosimetry data from nine patients who underwent permanent prostate brachytherapy
      served as the source of clinical data for this simulation study. Gaussian noise
      with standard deviations ranging from 0.5 to 10 mm was applied to the seed
      coordinates for each patient dataset and 1000 simulations were performed at each
      noise level. Dose parameters, including D90, were computed for each case and
      compared with the actual dosimetry data. A total of 81 000 complete sets of post
      brachytherapy dose volume statistics were computed. The results demonstrated that
      less than 5% deviation of prostate D90 can be expected when the seed localization
      uncertainty is 2 mm, whereas a seed localization uncertainty of 10 mm yielded an
      average decrease in D90 of 33 Gy. The mean normalized decrement in the prostate
      V100 was 10% at 5 mm uncertainty. Implants with greater seed number and larger
      prostate volume correlated with less sensitivity of D90 and V100 to seed
      localization uncertainty. Estimated target volume dose parameters tended to
      decrease with increasing seed localization uncertainty. The bladder V100 varied
      more significantly both in mean and standard deviation as compared to the urethra
      V100. A larger number of implanted seeds also correlated to less sensitivity of
      the bladder V100 to seed localization uncertainty. In contrast, the deviation of
      urethra V100 did not correlate with the number of implanted seeds or prostate
      volume.

PMID- 17505093
TI  - Verification of cell irradiation dose deposition using a radiochromic film.
AB  - We describe a technique for the MTT assay that irradiates all cells at once by a
      combination of couch movement and a step-and-shoot irradiation technique on a
      linear accelerator with 6 MV and 18 MV photon beams. In two experimental setups,
      we obtained maximum to minimum dose ranges of 10 for the constant MU/bin (monitor
      units per bin) setup and 20 for the variable MU/bin technique. The irradiation
      technique described is dose rate independent and it can be used on any
      teletherapy irradiation machine. We also employed radiochromic film dosimetry to
      verify dose delivered in each of the wells within the dish. It is shown that for
      the lowest doses, relative dose variation within wells reaches a value of 6%. We
      also demonstrated that the radiochromic film positioned below the 96-well plate
      does not underestimate dose deposited within each compartment by more than 2% due
      to the vertical dose gradient.

PMID- 17505094
TI  - Derivation of site-specific skeletal masses within the current ICRP age series.
AB  - The calculation of absorbed dose to the radiosensitive tissues of the skeleton is
      routinely performed using reference masses provided in publications from the
      International Commission on Radiological Protection (ICRP). These values
      typically include total skeleton tissue masses by reference subject age, but not
      by individual bone site at a given age. Site-specific variations in absorbed
      fractions are known to occur for internal alpha-particle and beta-particle
      emitters, and in certain medical dose reconstructions, site-specific estimates of
      marrow dose may be desirable. Furthermore, bone-site-specific tissue masses are
      required to properly estimate skeletal-averaged absorbed fractions and, more
      importantly, specific absorbed fractions for internalized radionuclides and
      radiopharmaceuticals. Reference masses by skeletal site are also needed in the
      development of ICRP compliant tomographic phantoms, as this organ system is
      initially segmented from medical images only as a homogeneous tissue region. ICRP
      reference skeletal masses are assigned based upon several independent data
      sources, many of which may not be entirely consistent with one another. In this
      study, a methodology is presented, using data from the various ICRP publications,
      to derive site-specific skeletal tissue masses for each member of the ICRP age
      series. Active marrow masses are calculated and differences are shown with
      respect to ICRP Publications 70 and 89 values. New data for a revised surrogate
      tissue region for the osteoprogenitor cells within bone marrow is presented with
      estimates of its total mass throughout the skeleton and for different subject
      ages.

PMID- 17505095
TI  - A beam source model for scanned proton beams.
AB  - A beam source model, i.e. a model for the initial phase space of the beam, for
      scanned proton beams has been developed. The beam source model is based on
      parameterized particle sources with characteristics found by fitting towards
      measured data per individual beam line. A specific aim for this beam source model
      is to make it applicable to the majority of the various proton beam systems
      currently available or under development, with the overall purpose to drive dose
      calculations in proton beam treatment planning. The proton beam phase space is
      characterized by an energy spectrum, radial and angular distributions and
      deflections for the non-modulated elementary pencil beam. The beam propagation
      through the scanning magnets is modelled by applying experimentally determined
      focal points for each scanning dimension. The radial and angular distribution
      parameters are deduced from measured two-dimensional fluence distributions of the
      elementary beam in air. The energy spectrum is extracted from a depth dose
      distribution for a fixed broad beam scan pattern measured in water. The impact of
      a multi-slab range shifter for energy modulation is calculated with an own Monte
      Carlo code taking multiple scattering, energy loss and straggling, non-elastic
      and elastic nuclear interactions in the slab assembly into account. Measurements
      for characterization and verification have been performed with the scanning
      proton beam system at The Svedberg Laboratory in Uppsala. Both in-air fluence
      patterns and dose points located in a water phantom were used. For verification,
      dose-in-water was calculated with the Monte Carlo code GEANT 3.21 instead of
      using a clinical dose engine with approximations of its own. For a set of four
      individual pencil beams, both with the full energy and range shifted, 96.5%
      (99.8%) of the tested dose points satisfied the 1%/1 mm (2%/2 mm) gamma
      criterion.

PMID- 17505096
TI  - Monte Carlo modelling of singles-mode transmission data for small animal PET
      scanners.
AB  - The attenuation corrections factors (ACFs), which are necessary for
      quantitatively accurate PET imaging, can be obtained using singles-mode
      transmission scanning. However, contamination from scatter is a largely
      unresolved problem for these data. We present an extension of the Monte Carlo
      simulation tool, GATE, for singles-mode transmission data and its validation
      using experimental data from the microPET R4 and Focus 120 scanners. We first
      validated our simulated PET scanner for coincidence-mode data where we found that
      experimental resolution and scatter fractions (SFs) agreed well for simulations
      that included positron interactions and scatter in the source material. After
      modifying GATE to model singles-mode data, we compared simulated and experimental
      ACFs and SFs for three different sized water cylinders using 57Co (122 keV photon
      emitter) and 68Ge (positron emitter) transmission sources. We also propose a
      simple correction for a large background contamination we identified in the 68Ge
      singles-mode data due to intrinsic 176Lu radioactivity present in the detector
      crystals. For simulation data, the SFs agreed to within 1.5% and 2.5% of
      experimental values for background-corrected 68Ge and 57Co transmission data,
      respectively. This new simulation tool accurately models the photon interactions
      and data acquisition for singles-mode transmission scans.

PMID- 17505097
TI  - Contrast-to-noise ratio in magnification mammography: a Monte Carlo study.
AB  - Magnification views are a common way to perform a secondary examination when
      suspicious abnormalities are found in a screening mammogram. The visibility of
      microcalcifications and breast lesions is restricted by the compromise between
      the image quality and the absorbed dose. In this study, image quality
      characteristics in magnification mammography were evaluated based on Monte Carlo
      techniques. A breast phantom was utilized, simulating a homogeneous mixture of
      adipose and glandular tissue in various percentages of glandularity, containing
      inhomogeneities of various sizes and compositions. The effect of the
      magnification degree, breast glandularity, tube voltage and anode/filter material
      combination on image quality characteristics was investigated in terms of a
      contrast-to-noise ratio (CNR). A performance index PI(nu) was introduced in order
      to study the overall performance of various anode/filter combinations under
      different exposure parameters. Results demonstrate that CNR is improved with the
      degree of magnification and degraded as the breast glandularity is increased.
      Degree of magnification 1.3 offers the best overall performance for most of the
      anode/filter combinations utilized. Under magnification conditions, the role of
      dose is demoted against the image quality, as magnification views are secondary,
      diagnostic examinations and not screening procedures oriented to non-symptomatic
      women. For decreased image quality weighting, some anode/filter combinations
      different from Mo/0.030 mmMo can be utilized as they offer a similar performance
      index. However, if the desired weighting for the image quality is high, the
      Mo/0.030 mmMo combination has the best overall performance.

PMID- 17505098
TI  - Improved k-t BLAST and k-t SENSE using FOCUSS.
AB  - The dynamic MR imaging of time-varying objects, such as beating hearts or brain
      hemodynamics, requires a significant reduction of the data acquisition time
      without sacrificing spatial resolution. The classical approaches for this goal
      include parallel imaging, temporal filtering and their combinations. Recently,
      model-based reconstruction methods called k-t BLAST and k-t SENSE have been
      proposed which largely overcome the drawbacks of the conventional dynamic imaging
      methods without a priori knowledge of the spectral support. Another recent
      approach called k-t SPARSE also does not require exact knowledge of the spectral
      support. However, unlike k-t BLAST/SENSE, k-t SPARSE employs the so-called
      compressed sensing (CS) theory rather than using training. The main contribution
      of this paper is a new theory and algorithm that unifies the above mentioned
      approaches while overcoming their drawbacks. Specifically, we show that the
      celebrated k-t BLAST/SENSE are the special cases of our algorithm, which is
      asymptotically optimal from the CS theory perspective. Experimental results show
      that the new algorithm can successfully reconstruct a high resolution cardiac
      sequence and functional MRI data even from severely limited k-t samples, without
      incurring aliasing artifacts often observed in conventional methods.

PMID- 17505099
TI  - Fan-beam filtered-backprojection reconstruction without backprojection weight.
AB  - In this paper, we address the problem of two-dimensional image reconstruction
      from fan-beam data acquired along a full 2pi scan. Conventional approaches that
      follow the filtered-backprojection (FBP) structure require a weighted
      backprojection with the weight depending on the point to be reconstructed and
      also on the source position; this weight appears only in the case of divergent
      beam geometries. Compared to reconstruction from parallel-beam data, the
      backprojection weight implies an increase in computational effort and is also
      thought to have some negative impacts on noise properties of the reconstructed
      images. We demonstrate here that direct FBP reconstruction from full-scan fan
      beam data is possible with no backprojection weight. Using computer-simulated,
      realistic fan-beam data, we compared our novel FBP formula with no backprojection
      weight to the use of an FBP formula based on equal weighting of all data.
      Comparisons in terms of signal-to-noise ratio, spatial resolution and
      computational efficiency are presented. These studies show that the formula we
      suggest yields images with a reduced noise level, at almost identical spatial
      resolution. This effect increases quickly with the distance from the center of
      the field of view, from 0% at the center to 20% less noise at 20 cm, and to 40%
      less noise at 25 cm. Furthermore, the suggested method is computationally less
      demanding and reduces computation time with a gain that was found to vary between
      12% and 43% on the computers used for evaluation.

PMID- 17505100
TI  - The feasibility of estimating and imaging the mechanical behavior of poroelastic
      materials using axial strain elastography.
AB  - In this paper, we have investigated the feasibility of imaging the mechanical
      behavior of poroelastic materials using axial strain elastography. Cylindrical
      samples obtained from poroelastic materials having different elastic and
      permeability properties were subjected to a constant compression force (a
      classical creep experiment), during which poroelastographic data were acquired.
      For comparison, we also tested a few gelatin phantoms and non-homogeneous
      poroelastic phantoms constructed by combining different poroelastic materials.
      From the acquired data, we generated time-dependent sequences of axial strain
      elastograms and effective Poisson's ratio elastograms, which were then used for
      generating axial strain and effective Poisson's ratio time-constant elastograms.
      Thereafter, the various poroelastographic images were analyzed to evaluate the
      presence of statistically significant differences among the two types of
      poroelastic samples and for image quality analysis. The results of this study
      demonstrate that it is technically feasible to use axial strain elastography to
      distinguish among homogeneous poroelastic materials characterized by different
      elastic and permeability properties. They also show that the use of axial strain
      elastography instead of effective Poisson's ratio elastography results in
      objectively higher quality poroelastograms of the temporal behavior of the
      poroelastic materials under loading. However, the use of effective Poisson's
      ratio elastography may in any case be required to verify that the temporal
      changes occurring in the axial strains of the homogeneous poroelastic samples are
      also accompanied by temporal changes of the effective Poisson's ratios and are
      therefore due to poroelastic behavior.

PMID- 17505101
TI  - Factors influencing fast low angle positive contrast steady-state free precession
      (FLAPS) magnetic resonance imaging.
AB  - The presence of susceptibility-shifting media can lead to signal voids in
      magnetic resonance images. While signal voids have been traditionally used to
      detect such magnetic perturbers, selective magnetic resonance imaging of off
      resonant spins surrounding susceptibility-shifted media allows for them to be
      visualized as hyper-intense (positive contrast) regions. These positive contrast
      methods can potentially improve the detection conspicuity of magnetic perturbers
      against regions that appear dark due to the absence of protons, such as air.
      Recently, a fast low angle positive contrast steady-state free precession (FLAPS)
      technique has been proposed as a positive contrast imaging method. This work
      systematically evaluates the contrast characteristics and acquisition strategies
      of FLAPS-based imaging from the standpoint of imaging parameters and physical
      properties of the magnetic perturbers. Results show that scan parameters (T(R),
      flip angle, B0), physical properties of the perturber (size and concentration of
      shift reagent) and the ratio of the relaxation constants (T1/T2) of the medium
      are significant factors influencing the FLAPS-based positive contrast.

PMID- 17505102
TI  - Monte Carlo modeling of the ModuLeaf miniature MLC for small field dosimetry and
      quality assurance of the clinical treatment planning system.
AB  - The purpose of this investigation was the verification of both the measured data
      and quality of the implementation of the add-on ModuLeaf miniature multileaf
      collimator (ML mMLC) into the clinical treatment planning system for conformal
      stereotactic radiosurgery treatment. To this end the treatment head with ML mMLC
      was modeled in the BEAMnrc Monte Carlo (MC) code. The 6 MV photon beams used in
      the setup were first benchmarked with a set of measurements. A total ML mMLC
      transmission of 1.13% of the 10 x 10 cm2 open field dose was measured and
      reproduced with the BEAMnrc/DOSXYZnrc code. Correspondence between calculated and
      measured output factors (OFs) was within 2%. Correspondence between MC and
      measured profiles was within 2% dose and 2 mm distance, only for the smallest 0.5
      x 0.5 cm2 field the results were within 3% dose. In the next step, the MC model
      was compared with Gafchromic film measurements and Pinnacle(3) 7.4 f (convolution
      superposition algorithm) calculated dose distributions, using a gamma evaluation
      comparison, for a multi-beam patient setup delivered to a Lucytrade mark phantom.
      The gamma evaluation of the MC versus Gafchromic film resulted in 3.4% of points
      not fulfilling gamma <or= 1 for a 2%/2 mm criterion, the Pinnacle(3) 7.4 f versus
      Gafchromic results 3.8% and Pinnacle versus MC less than 1%. For specific
      patients with lesions of 8 cc and 0.2 cc, Monte Carlo and Pinnacle simulations of
      the plans were performed and compared using DVH evaluation. DVHs corresponded
      within 2% dose and 2% volume.

PMID- 17505103
TI  - Mathematical modeling of brain tumors: effects of radiotherapy and chemotherapy.
AB  - Gliomas, the most common primary brain tumors, are diffusive and highly invasive.
      The standard treatment for brain tumors consists of a combination of surgery,
      radiation therapy and chemotherapy. Over the past few years, mathematical models
      have been applied to study untreated and treated brain tumors. In an effort to
      improve treatment strategies, we consider a simple spatio-temporal mathematical
      model, based on proliferation and diffusion, that incorporates the effects of
      radiotherapeutic and chemotherapeutic treatments. We study the effects of
      different schedules of radiation therapy, including fractionated and
      hyperfractionated external beam radiotherapy, using a generalized linear
      quadratic (LQ) model. The results are compared with published clinical data. We
      also discuss the results for combination therapy (radiotherapy plus temozolomide,
      a new chemotherapy agent), as proposed in recent clinical trials. We use the
      model to predict optimal sequencing of the postoperative (combination of
      radiotherapy and adjuvant, neo-adjuvant or concurrent chemotherapy) treatments
      for brain tumors.

PMID- 17505104
TI  - The atomic resolution structure of human aldose reductase reveals that
      rearrangement of a bound ligand allows the opening of the safety-belt loop.
AB  - The crystal structure of human aldose reductase in complex with citrate has been
      determined to a resolution of 0.82 A. The difference electron density for H atoms
      unequivocally shows that the cofactor is in the oxidized state corresponding to
      the situation after the catalytic event has occurred. A citrate molecule bound to
      the active site has been modelled in two different conformations. These two
      conformations correlate with a fully closed and a partially open conformation of
      the so-called safety-belt loop (Gly213-Ser226). The open conformation is observed
      for the first time with the cofactor bound to the protein and may be related to
      the initial phase of the opening of the safety belt. The structure suggests that
      after the catalytic event, a rearrangement of a bound ligand can trigger the
      opening of the safety-belt loop, thus initiating the release of the oxidized
      cofactor.

PMID- 17505105
TI  - The structure of a d(gcGAACgc) duplex containing two consecutive bulged A
      residues in both strands suggests a molecular switch.
AB  - In previous studies, it was reported that DNA fragments with the sequence
      d(gcGXYAgc) (where X = A or G and Y = A, T or G) form a stable base-intercalated
      duplex (Bi-duplex) in which the central X and Y residues are not involved in any
      base-pair interactions but are alternately stacked on each other between the two
      strands. To investigate the structural stability of the Bi-duplex, the crystal
      structure of d(gcGAACgc) with a point mutation at the sixth residue of the
      sequence, d(gcGAAAgc), has been determined. The two strands are associated in an
      antiparallel fashion to form two types of bulge-containing duplexes (Bc
      duplexes), I and II, both of which are quite different from the Bi-duplex of the
      parent sequence. In both Bc-duplexes, three Watson-Crick G.C base pairs
      constitute the stem regions at the two ends. The A(4) residues are bulged in to
      form a pair with the corresponding A(4) residue of the opposite strand in either
      duplex. The A(4).A(4)* pair formation is correlated to the orientations of the
      adjacent A(5) residues. A remarkable difference between the two Bc-duplexes is
      seen at the A(5) residue. In Bc-duplex I, it is flipped out and comes back to
      interact with the G(3) residue. In Bc-duplex II, the A(5) residue extends
      outwards to interact with the G(7) residue of the neighbouring Bc-duplex I. These
      results indicate that trans sugar-edge/Hoogsteen (sheared-type) G(3).A(6)* base
      pairs are essential in the formation of a Bi-duplex of d(gcGXYAgc). On the other
      hand, the alternative conformations of the internal loops containing two
      consecutive bulged A residues suggest molecular switching.

PMID- 17505106
TI  - Structure of a d(TGGGGT) quadruplex crystallized in the presence of Li+ ions.
AB  - A parallel 5'-d(TGGGGT)-3' quadruplex was formed in Na(+) solution and
      crystallized using lithium sulfate as the main precipitating agent. The X-ray
      structure was determined to 1.5 A resolution in space group P2(1) by molecular
      replacement. The asymmetric unit consists of a characteristic motif of two
      quadruplexes stacked at their 5' ends. All nucleotides are clearly defined in the
      density and could be positioned. A single bound Li(+) ion is observed at the
      surface of the column formed by the two joined molecules. Thus, this small alkali
      metal ion appears to be unsuitable as a replacement for the Na(+) ion in the
      central channel of G-quartets, unlike K(+) or Tl(+) ions. A well conserved
      constellation of water molecules is observed in the grooves of the dimeric
      structure.

PMID- 17505107
TI  - Probing the S2 site of factor VIIa to generate potent and selective inhibitors:
      the structure of BCX-3607 in complex with tissue factor-factor VIIa.
AB  - Factor VIIa (FVIIa) is a trypsin-like serine protease in the coagulation cascade.
      Its complex with tissue factor (TF) triggers the extrinsic pathway of the
      coagulation cascade, generating a blood clot. Research programs at several
      centers now recognize the important roles played by TF and FVIIa in both the
      thrombotic and inflammatory processes associated with cardiovascular diseases.
      Therefore, inhibition of the TF-FVIIa complex is seen as a promising target that
      is key to the development of clinical candidates for various cardiovascular
      applications. The crystal structure of the TF-FVIIa enzyme complex has been
      analyzed in order to design and synthesize small-molecule inhibitors. Using
      structure-based drug design (SBDD), a new series of inhibitors have been
      discovered that demonstrate high potency against the TF-FVIIa complex while
      maintaining substantial selectivity versus other closely related serine proteases
      such as trypsin, thrombin, factor Xa and plasmin.

PMID- 17505108
TI  - Structure-assisted discovery of Variola major H1 phosphatase inhibitors.
AB  - Variola major virus, the causative agent of smallpox, encodes the dual
      specificity H1 phosphatase. Because this enzyme is essential for the production
      of mature virus particles, it is an attractive molecular target for the
      development of therapeutic countermeasures for this potential agent of
      bioterrorism. As a first step in this direction, the crystal structure of H1
      phosphatase has been determined at a resolution of 1.8 A. In silico screening
      methods have led to the identification of several small molecules that inhibit
      Variola H1 phosphatase with IC(50) values in the low micromolar range. These
      molecules provide novel leads for future drug development.

PMID- 17505109
TI  - On the application of molecular-dynamics simulations to validate thermal
      parameters and to optimize TLS-group selection for macromolecular refinement.
AB  - Comparison of crystallographically determined and molecular dynamics simulation
      derived parameters for a small (26 kDa) homotetrameric four-alpha-helical bundle
      protein revealed an unexpected pattern of similarities and differences between
      experiment and simulation. On one hand, the protein structure per se is
      exceptionally well preserved during the simulations, with a root-mean-square
      deviation between the C(alpha) atoms of the crystal structure and the simulation
      derived average structures of only 0.58 A, which is not very different from the
      expected coordinate error of the experimentally determined structure. On the
      other hand, comparison of the temperature factors showed a large discrepancy,
      with the experimental B factors being approximately three times higher than the
      simulation-derived B factors. Closer examination of this discrepancy appears to
      validate the molecular-dynamics prediction and to implicate as its source static
      disorder at the crystalline state, as indicated by the strong diffuse scattering
      and pronounced anisotropy of the diffraction pattern of the protein crystals. A
      posteriori re-refinement of the structure using a new TLS parameterization scheme
      based on the results obtained from the simulations led to a further reduction of
      the R factor and the free R value by 0.4% and 0.8%, respectively, indicating that
      molecular-dynamics simulations have matured to the point that they can be used to
      aid the selection of TLS groups for macromolecular refinement.

PMID- 17505110
TI  - Crystal structure of CD59: implications for molecular recognition of the
      complement proteins C8 and C9 in the membrane-attack complex.
AB  - Human CD59 is a small membrane-bound glycoprotein that functions as an inhibitor
      of the membrane-attack complex (MAC) of the complement system by binding the
      complement proteins C8 and C9. The crystal structure of a soluble construct of
      CD59 has been determined to 2.1 A resolution. When compared with previous models
      of CD59 determined using NMR, some interesting differences are noted, including
      the position of helix alpha1, which contributes to the binding surface for C8 and
      C9. Interestingly, the crystal structure superimposes more closely with an
      updated NMR model of CD59 that was produced using Monte Carlo minimization,
      including helix alpha1. Mapping of mutations associated with enhanced or lowered
      inhibitory function of CD59 show the binding region to be located in a crevice
      between alpha1 and a three-stranded beta-sheet, as has been identified
      previously. Residues in the core of this region are well ordered in the electron
      density, in part owing to a network of stabilizing covalent and noncovalent
      interactions, and manifest an interesting 'striped' distribution of hydrophobic
      and basic residues. Docking of the same peptide that was modeled previously into
      the NMR structure shows that Arg55, which has been postulated to exist in 'open'
      and 'closed' positions, is intermediate in position between these two and is well
      placed to contact the peptide. Further clues regarding how CD59 interacts with
      small peptides arise from the crystal packing of this structure, which shows that
      a symmetry-related loop comprising residues 20-24 occupies a spatially similar
      position to the modeled peptide. This higher resolution structure of CD59 will
      facilitate a more precise dissection of its interactions with C8 and C9 and thus
      increase the likelihood of designing enhanced CD59-based therapeutics.

PMID- 17505111
TI  - Structural and pharmacological comparison of daboiatoxin from Daboia russelli
      siamensis with viperotoxin F and vipoxin from other vipers.
AB  - Russell's viper (Vipera russelli, also known as Daboia russelli) is one of the
      major causes of fatal snakebites. To date, five Daboia russelli subspecies have
      been recognized. Daboiatoxin (DbTx) is the main lethal phospholipase A(2)
      (PLA(2)) toxin in the venom of D. russelli siamensis (Myanmar viper) and has
      strong neurotoxic, myotoxic and cytotoxic activities. DbTx and its homologous
      neurotoxins viperotoxin F from D. russelli formosensis (Taiwan viper) and vipoxin
      from the Bulgarian sand viper V. ammodytes meridionalis consist of complexes
      between a nontoxic acidic PLA(2) protein and an enzymatically active basic
      PLA(2). DbTx and viperotoxin F are presynaptic toxins, while vipoxin is
      postsynaptic. The two chains of DbTx have been separated and their PLA(2)
      enzymatic activity has been measured using the secretory PLA(2) assay kit. The
      enzymatic activity of DbTx chain B is reduced by 30% of its original activity by
      chain A in a unimolar ratio, thus indicating that DbTx chain A acts as an
      inhibitor. The lethal activity of the two chains has also been studied in male
      albino mice and chain A is less lethal than chain B. The crystal structure of
      DbTx has also been determined and its structural details are compared with those
      of the two homologues. Furthermore, an attempt is made to correlate the sequence
      and structural determinants of these toxins with their enzymatic activities and
      their pharmacological effects.

PMID- 17505112
TI  - Structure of human upstream binding factor HMG box 5 and site for binding of the
      cell-cycle regulatory factor TAF1.
AB  - The fifth HMG-box domain in human upstream binding factor (hUBF) contributes to
      the synthesis of rRNA by RNA polymerase I (Pol I). The 2.0 A resolution crystal
      structure of this protein has been solved using the single-wavelength anomalous
      dispersion method (SAD). The crystal structure and the reported NMR structure
      have r.m.s. deviations of 2.18-3.03 A for the C(alpha) atoms. However, there are
      significant differences between the two structures, with displacements of up to
      9.0 A. Compared with other HMG-box structures, the r.m.s. deviations for C(alpha)
      atoms between hUBF HMG box 5 and HMG domains from Drosophila melanogaster protein
      D and Rattus norvegicus HMG1 are 1.5 and 1.6 A, respectively. This indicates that
      the differences between the crystal and NMR structures of hUBF HMG box 5 are
      larger than those with its homologous structures. The differences between the two
      structures potentially reflect two states with different structures. The specific
      interactions between the hUBF HMG box 5 and the first bromodomain of TBP
      associated factor 1 (TAF1) were studied by ultrasensitive differential scanning
      calorimetry and chemical shift perturbation. Based on these experimental data,
      possible sites in hUBF HMG box 5 that may interact with the first bromodomain of
      TAF1 were proposed.

PMID- 17505113
TI  - Structure of the Streptococcus agalactiae family II inorganic pyrophosphatase at
      2.80 A resolution.
AB  - Streptococcus agalactiae, a prokaryote that causes infections in neonates and
      immunocompromised adults, has a serine/threonine protein kinase (STK) signalling
      cascade. The structure of one of the targets, a family II inorganic
      pyrophosphatase, has been solved by molecular replacement and refined at 2.80 A
      resolution to an R factor of 19.2% (R(free) = 26.7%). The two monomers in the
      asymmetric unit are related by a noncrystallographic twofold axis, but the
      biological dimer is formed by a crystallographic twofold. Each monomer contains
      the pyrophosphate analogue imidodiphosphate (PNP) and three metal ions per active
      site: two Mn(2+) ions in sites M1 and M2 and an Mg(2+) ion in site M3. The enzyme
      is in the closed conformation. Like other family II enzymes, the structure
      consists of two domains (residues 1-191 and 198-311), with the active site
      located between them. The conformation of Lys298 in the active site is different
      from those observed previously and it coordinates to the conserved DHH motif in a
      unique way. The structure suggests that Ser150, Ser194, Ser195 and Ser296 are the
      most likely targets for the Ser/Thr kinase and phosphatase because they are
      surface-accessible and either in the active site or in the hinge region between
      the two domains.

PMID- 17505114
TI  - Pseudo-merohedral twinning in monoclinic crystals of human orotidine-5'
      monophosphate decarboxylase.
AB  - Human UMP synthase is a bifunctional enzyme that catalyzes the penultimate and
      last steps in the de novo biosynthesis of UMP. In contrast to prokaryotes, UMP
      synthase from higher eukaryotes combines the orotate phosphoribosyltransferase
      and the orotidine-5'-monophosphate (OMP) decarboxylase activities on a single
      polypeptide chain. The decarboxylase activity is unusual in that it represents
      the fastest rate acceleration of any enzyme studied to date. Although several
      crystal structures of OMP decarboxylases have been described, the precise
      decarboxylation mechanism remains elusive. The crystal structure of the OMP
      decarboxylase domain from human UMP synthase was determined by molecular
      replacement using data from a highly twinned monoclinic crystal. The space group
      is P2(1), with unit-cell parameters a = 69.18, b = 61.70, c = 69.17 A, beta =
      113.06 degrees. Self-rotation function analysis and various intensity statistics
      revealed the presence of pseudo-merohedral twinning, but these tests
      underestimated the true twin fraction of alpha approximately = 0.44. Data
      analysis, the origin of the twinning and structure determination are discussed.

PMID- 17505116
TI  - Osteoporosis: a pediatric concern?
AB  - Osteoporosis and related fractures are a major public health concern globally,
      and the incidence and subsequent morbidity, mortality and health care costs are
      expected to increase dramatically over the coming decades. Although osteoporosis
      was once considered (primarily) a disease of the elderly, there is now universal
      agreement that the condition has pediatric antecedents. Although genetic factors
      play an important role in the attainment of an optimal adult (peak) bone mass and
      strength, lifestyle factors such as physical activity and nutrition are also
      important determinants of children's bone development. However, there is still
      much research needed to identify the exact role of modifiable lifestyle factors
      and childhood illness on long-term adult bone health and fracture risk. Much of
      our current knowledge is based on bone mineral content and areal bone mineral
      density assessed by dual-energy X-ray absorptiometry; but with rapidly advancing
      technology, researchers will be able to more accurately assess other indices of
      bone strength, such as the material and structural properties of bone, during the
      growing years. Based on our current knowledge, however, it is clear that
      intervention strategies aimed at reducing the incidence of osteoporosis must
      begin in childhood or adolescence if they are to have maximal effect.

PMID- 17505117
TI  - The biomechanical basis of bone strength development during growth.
AB  - Understanding the development of the material composition and structure of bone
      during growth, both key determinants of bone strength, and identifying factors
      that regulate the development of these properties are important for developing
      effective lifestyle interventions to optimize peak bone strength. New imaging
      technologies provide the ability to measure estimates of both the material
      composition and structure of bone, and thus, estimates of whole bone strength.
      During childhood and adolescence, bone structure is altered by growth in length
      and width, which is associated with increases in mass, and alterations in tissue
      density. These processes lead to a bone with an optimal size, shape, and
      architecture to withstand the normal physiological loads imposed on it.
      Longitudinal bone growth is the result of endochondral ossification, a process
      that continues throughout childhood and rapidly increases during the adolescent
      growth spurt. Along the shaft, long bones continually grow in width, thus
      improving the resistance to bending forces by depositing new bone on the
      periosteal surface with simultaneous resorption on the endocortical surface.
      Sexual dimorphism in periosteal bone formation and endosteal bone resorption
      result in sex-specific differences in adult bone conformation. Changes in linear
      and periosteal growth are closely tied to changes in bone mass, with
      approximately one quarter of adult total body bone mineral accrued during the 2
      years around the adolescent growth spurt. These structural and material changes
      are under mechanical regulation and influenced by the hormonal environment.
      Overall, bones must continually adapt their geometry and mass to withstand loads
      from increases in bone length, muscle mass and external forces during growth.
      However, the tempo, timing, and extent of such adaptations are also closely
      regulated by several systemic hormones.

PMID- 17505118
TI  - The effect of exercise on bone mass and structural geometry during growth.
AB  - Regular weight-bearing exercise is widely reported to have beneficial effects on
      bone mineral content and areal bone mineral density during growth, but the
      structural basis underlying these changes remains uncertain. In young athletic
      children, participation in high-impact sports has been shown to enhance bone
      formation on the periosteal and/or endosteal surfaces of long bones at loaded
      skeletal sites. Participation in moderate physical activity, recreational play or
      school-based exercise interventions designed to specifically load bone have also
      been shown to enhance bone mineral accrual. However, few data are available on
      the surface-specific effects of exercise training or general physical activity on
      bone. Based on the limited data available, it would appear that the structural
      response of bone to exercise during growth is maturity dependent and sex
      specific; prior to puberty exercise appears to increase periosteal apposition in
      both sexes, whereas during or late in puberty exercise appears to result in
      periosteal expansion in boys but endocortical contraction in girls. In most
      cases, these geometric changes lead to an increase in bone bending strength.
      However, there are contrasting results as to whether the pre- or peripubertal
      years are an optimal time to intervene for the greatest osteogenic response; it
      is likely that both periods represent an important time for incorporating
      physical activity to optimize bone health. There are also many unresolved
      questions as to the optimal dose of exercise (intensity, frequency, duration and
      rate of progression) needed to enhance bone strength in children and adolescents.
      We know that weight-bearing exercise is important, and that activities should be
      dynamic, variable in nature, applied rapidly and intermittently, and that
      relatively few loading cycles are required. Although several effective
      interventions have been designed for improving bone mass, further research is
      needed to define the specific exercise programs or activities that will optimize
      bone structure and strength during growth. Perhaps most importantly, further work
      is also needed to determine whether any exercise-induced alterations in bone mass
      and structure during growth are maintained into old age when fractures occur.

PMID- 17505119
TI  - Evidence for an interaction between exercise and nutrition for improved bone
      health during growth.
AB  - Exercise and nutrition are independently recognized as important modifiable
      lifestyle factors essential for optimal bone health during growth. In this
      review, we discuss the effect of dietary calcium, vitamin D and protein alone and
      in combination with exercise on bone mass and strength in children and
      adolescents. Recent intervention studies in children now provide evidence that
      exercise and calcium may interact with each other to enhance bone health, but the
      mechanism underlying this effect is not well understood. Vitamin D is also
      important for bone health through its action on calcium absorption, and both
      dietary protein and total energy intake can also alter bone metabolism through
      their influence on growth factors such as insulin-like growth factor I. However,
      whether these factors act synergistically with exercise to enhance bone accrual
      has not been examined. Therefore, while exercise and nutrition are both
      independently important for skeletal development, there remain many unanswered
      questions as to whether combinations of these factors interact to enhance
      skeletal health during growth. Current evidence suggests that regular weight
      bearing exercise and adequate dietary calcium intakes (around 1,000 mg per day)
      may be required to optimize bone health; however, exercise would appear to be
      more important for optimizing bone strength because it has a direct effect (e.g.
      via loading) on bone mass and structural properties, whereas nutritional factors
      appear to have an indirect effect (e.g. via hormonal factors) on bone mass.

PMID- 17505120
TI  - Gene-environment interactions in the skeletal response to nutrition and exercise
      during growth.
AB  - The amount of bone mineral mass acquired at the end of growth, the so-called
      'peak bone mass', is considered to be a major risk factor for the occurrence of
      fragility fractures during adult life. Many interrelated factors can influence
      the accumulation of bone mass during growth, including genetics, sex, ethnicity,
      nutrition (e.g. calcium, vitamin D, protein), hormonal factors (e.g. sex
      steroids, insulin-like growth factor I), physical activity and exposure to
      various risk factors (e.g. alcohol, smoking, certain medications). Family and
      twin studies have estimated that up to 60-80% of the variance in peak bone mass
      is attributable to genetic factors. It can be predicted from epidemiological
      studies that a 10% increase in peak bone mass would reduce the risk of fragility
      fractures after the menopause by 50%. Intervention studies testing the effects of
      increasing either calcium intake or physical activity during growth provide
      evidence that modifying environmental factors can positively influence peak bone
      mass. Nevertheless, there is large interindividual variability in the response
      suggesting gene-environment interactions. A few studies have reported
      associations between some bone-related gene polymorphisms and the osteogenic
      response to loading or calcium supplementation. Identifying the functionally
      implicated genes interacting with mechanical loading and/or specific nutrients
      represents a formidable but hopefully not intractable challenge.

PMID- 17505121
TI  - The effect of energy balance on endocrine function and bone health in youth.
AB  - Female athletes are susceptible to both disordered eating and menstrual cycle
      disturbances (MCDs). Disordered eating in combination with high energy
      expenditure from exercise can lead to energy deprivation. Current theories
      suggest that MCDs are caused by energy deprivation rather than by exercise alone.
      A number of endocrine adaptations occur with energy deprivation and MCDs, which
      are concomitant with imbalanced bone turnover, reduced bone density and
      potentially increased fracture risk. This chapter reviews current evidence
      concerning the disruption of bone metabolism that accompanies disordered eating
      and MCDs in physically active girls and young women, including high-performance
      athletes. Initially, an overview of the aetiology of exercise-associated MCDs and
      their link with disordered eating is provided. Thereafter, studies reporting
      changes in areal bone mineral density (aBMD) in female athletes with MCDs are
      considered in conjunction with change in athletes' physical activity, nutritional
      status and menstrual histories. A comprehensive overview of the disruption of
      bone metabolism that accompanies nutritionally related MCDs is also provided.
      Emphasis is placed upon the role of energy deprivation and its endocrine effects,
      which, when sustained, result in imbalanced bone turnover and low aBMD. Based on
      current evidence, recommendations are made for the prevention and treatment of
      disturbed bone metabolism and low BMD in female athletes with MCDs. Finally,
      consideration is given to the effects of intense training and energy deprivation
      on endocrine function and skeletal health in men.

PMID- 17505122
TI  - Risk factors for fractures in normally active children and adolescents.
AB  - Although many children sustain at least one fracture during growth, the majority
      do not, suggesting it is not the norm for healthy children to break their bones.
      Most childhood fractures occur during play and sport and result from mild or
      moderate, rather than severe trauma. The majority of fractures (86.4%) are
      treated solely in outpatient clinics. Furthermore, there is evidence that 66% of
      all fractures during growth occur in children and adolescents who fracture on
      more than one occasion, suggesting certain children may be predisposed to
      fracture. These individuals frequently fracture first at a young age (<5 years),
      and any previous history of fracture increases the risk of further fractures 2-
      to 3-fold. While rates of fracture vary considerably with age, sex and
      maturation, they peak in early puberty when rates of bone turnover are high but
      bone mineral accrual lags behind gains in height and weight. Fractures are also
      common in children with endocrine dysfunction, chronic illnesses or genetic
      disorders that affect bone metabolism and muscle mass, and/or require the use of
      medications that influence bone metabolism. A number of risk factors have been
      identified which may predispose children and adolescents to fracture. For
      instance, bone mineral content, bone size and bone accrual are all lower in
      apparently healthy children and adolescents with fractures, and low bone mineral
      density is a predictor of new fracture. There is also evidence that genetic
      factors, poor nutrition (including an inadequate intake of dietary calcium, milk
      avoidance and excessive consumption of carbonated beverages), lack of weight
      bearing physical activity, obesity and high exposure to trauma may influence
      fracture risks in the general pediatric population.

PMID- 17505123
TI  - Does exercise during growth prevent fractures in later life?
AB  - Regular weight-bearing exercise, especially during the pre- or early peripubertal
      years, leads to substantial benefits in bone mass and skeletal structure,
      enhancing bone strength at loaded sites. However, few fragility fractures occur
      in young adulthood, and only if the exercise-induced skeletal benefits are
      retained into older age, a time when the incidence of fragility fractures rises
      exponentially, would these changes be of biological significance for fracture
      reduction. The limited data available indicate that exercise benefits in areal
      bone mineral density are eroded in the long term. In contrast, several studies
      suggest that exercise-induced structural changes may be retained even following
      the cessation of exercise. These structural changes may be more important to
      overall bone strength than bone mass or density alone. In addition, residual
      benefits in nonskeletal factors, such as improved muscle strength, coordination
      and balance, may also reduce fracture risk. However, it is uncertain what
      actually happens to the fracture risk of individuals who retire from exercise and
      reduce their level of activity to that of the average individual. Recent
      retrospective observational and case-control studies suggest that there could be
      a reduced fracture risk in former athletes. However, since these studies are
      cross-sectional, no inferences could be drawn as regards causality. Selection
      bias at baseline would actually produce the same results. Furthermore, the
      biological explanation for the reduced fracture incidence is not clear although
      several explanations have been proposed, including: residual benefits to bone
      structural properties, muscle strength, coordination and balance. Each of these
      traits could be maintained in former athletes after their active career, and may
      help to reduce the number of fractures later in life. Therefore, based on the
      current evidence, we recommend a physically active lifestyle during growth as a
      possible preventive strategy against fragility fractures in old age.

PMID- 17505124
TI  - Lessons learned from school-based skeletal loading intervention trials: putting
      research into practice.
AB  - In recent years, there have been a number of school-based physical activity
      intervention trials aimed at optimizing bone development. Various approaches have
      been taken including interventions ranging from 3 to 50 min in length performed 2
      5 times per week incorporated within the school day (typically in physical
      education) or as an after-school program. Overall, these studies showed that
      school-based skeletal loading interventions are efficacious, safe, and feasible.
      Furthermore, studies to date have shown that interventions are most effective
      when initiated during prepuberty and early puberty, and consist of dynamic
      activities that are high in magnitude (i.e. jumping, skipping, hopping) and
      include multidirectional movements. Recent work also suggests that adding rest
      intervals and performing short bouts of activity a few times per day may enhance
      the effectiveness of loading on bone health. In this chapter, we discuss
      important training principles and lessons learned from these intervention trials
      and provide practical guidelines, tips and sample programs that can be used by
      health care professionals interested in optimizing bone health of children and
      adolescents.

PMID- 17505125
TI  - Age- and stress-induced changes in corticotropin-releasing hormone mRNA
      expression in the paraventricular nucleus of the hypothalamus.
AB  - In reaction to acute stress, prepubertal (25-28 days of age) animals demonstrate
      a prolonged adrenocorticotropic hormone (ACTH) and corticosterone response
      compared to adults (>65 days of age), while after chronic stress, prepubertal
      animals show a higher peak ACTH and corticosterone response, but a faster return
      to baseline compared to adults. Differential activation of corticotropin
      releasing hormone (CRH) neurons in the paraventricular nucleus of the
      hypothalamus (PVN) of prepubertal and adult animals have been suggested to
      mediate these changes in stress responsiveness. The purpose of the present set of
      experiments was to further elucidate possible differences in PVN structure and
      function in prepubertal (28 days of age) and adult (77 days of age) male rats.
      The results indicate that PVN volume and somal size and cell number are similar
      in the parvocellular and magnocellular subdivision of the PVN before and after
      pubertal development. Furthermore, after a peripheral injection of the retrograde
      tracer Fluoro-Gold (FG), prepubertal and adult males demonstrate similar numbers
      of anterior pituitary projecting neurosecretory neurons in the parvocellular
      region of the PVN. Finally, using in situ hybridization we show that in response
      to acute stress, CRH mRNA in the PVN was affected by both age and stress such
      that prepubertal males have greater CRH expression than adults and both
      prepubertal and adult males show significant stress-induced increases in CRH
      mRNA. Interestingly, in response to repeated restraint, neither age nor stress
      significantly influence CRH expression. Together, these data indicate that both
      age and experience with stress interact to modulate CRH expression in the PVN.

PMID- 17505126
TI  - Angiotensin-converting enzyme inhibitors and smoking cessation.

PMID- 17505127
TI  - Chronic airway diseases in adult life and childhood infections.
AB  - BACKGROUND: Respiratory disorders in childhood may predispose to pulmonary
      disease in late adult life. OBJECTIVES: The aim of this study was to evaluate the
      relationship between their effects in adult life and the characteristics of the
      respiratory system in childhood. METHODS: A total of 10,224 parents and
      grandparents of students from 14 randomly selected primary schools in the city
      center were asked to answer questionnaires given to their children. 9,853 of
      10,224 persons (the overall response rate was 96.3%) were eligible for analysis.
      In the questionnaire subjects were asked about respiratory system-related
      symptoms and characteristics. RESULTS: Chronic cough [14.3 vs. 4.7%, OR 3.4 (2.6
      4.4), p < 0.001], chronic bronchitis [35.3 vs. 11.8%, OR 4.0 (3.4-4.8), p <
      0.001] and asthma [34.2 vs. 5.1%, OR 9.6 (8.0-11.5), p < 0.001] in the childhood
      respiratory infection group were more common than in the control group. Childhood
      respiratory infections were associated with an increased risk of asthma (OR 5.6,
      p < 0.001), chronic bronchitis (OR 2.3, p < 0.001) and chronic cough (OR 1.5, p <
      0.001), after adjusting for possible confounding factors. In addition, the
      presence of dampness or visible mould, wall-to-wall carpets, pets at home and
      parents' smoking during childhood were associated with an increased risk of
      frequent childhood respiratory infections. CONCLUSION: These results indicated
      that frequent respiratory infections during childhood might play an important
      role in the occurrence of chronic airway diseases in adult life. The removing of
      risk factors for frequent childhood respiratory infections may reduce the
      subsequent risk of chronic airway disease in late adult life.

PMID- 17505128
TI  - Pulmonary hypertension in patients with chronic renal failure.
AB  - BACKGROUND: Many etiologies causing pulmonary hypertension (PH) have been
      reported, and one of the background disease seen with patients with PH is chronic
      renal failure (CRF); however, the pathogenesis of PH in this group of patients is
      not explained satisfactorily. OBJECTIVES: The aims of this study were to evaluate
      the incidence of unexplained PH among patients with CRF and to suggest possible
      etiologic factors. METHODS: Two hundred and eleven patients with CRF were
      evaluated and the ones who have comorbid conditions that cause PH were excluded.
      Pulmonary arterial pressure (PAP) and cardiac functions were evaluated by Doppler
      echocardiography. Arteriovenous fistula (AVF) flow was measured by Doppler
      sonography. The patients were followed for at least 6 months. RESULTS: Forty
      eight CRF patients (20 males, 28 females) were included: 23 were predialysis
      patients, and 25 patients received hemodialysis via AVF. Patients were followed
      for 7.5 +/- 1.01 months. Systolic PAP >35 mm Hg was found in 56% (14/25) of
      patients receiving hemodialysis (36.8 +/- 10.7 mm Hg) and in 39.1% (9/23) of
      predialysis patients (29.5 +/- 9.5 mm Hg). The parathyroid hormone level, cardiac
      output values and CRF duration were found to be increased in patients with
      elevated systolic PAP (p < 0.05). AVF flow and AVF duration were positively
      correlated with systolic PAP in patients receiving hemodialysis (p < 0.05). There
      was a negative correlation between systolic PAP and residual urine volume (p <
      0.05). AVF compression in hemodialysis patients decreased systolic PAP from 36.8
      +/- 10.7 to 32.8 +/- 10.5 mm Hg. Systolic PAP values were increased at the end of
      the study in the predialysis group, whereas they were decreased at the end of the
      follow-up in the hemodialysis group (36.9 +/- 10.5 and 32.04 +/- 10.5 mm Hg,
      respectively). CONCLUSIONS: This study demonstrates a high incidence of PH among
      patients with CRF. CRF duration, AVF flow, parathyroid hormone level and cardiac
      output may be involved in the pathogenesis of PH. The effective hemodialysis and
      dry weight reduction decreased systolic PAP values.

PMID- 17505129
TI  - Non-Hodgkin lymphomas concurrent with HHV8-associated Kaposi's sarcoma in the
      same lymph node in AIDS and non-AIDS patients.
AB  - BACKGROUND: The association between lymphomas and Kaposi's sarcoma has been
      described since 1920. The simultaneous presence of the 2 pathologic entities
      within the same lymph node is a rare and interesting occurrence. In the few cases
      described, the presence of human herpesvirus 8 (HHV8) and Epstein-Barr virus
      (EBV) in the different neoplastic areas was investigated only by
      immunohistochemistry and in situ hybridization studies. METHODS: Two cases of
      concurrent non-Hodgkin lymphoma and Kaposi's sarcoma in the same lymph node are
      described: a diffuse large B cell lymphoma in an AIDS patient and a T cell-rich
      large B cell lymphoma in a HIV-negative patient, complete with the clinical,
      immunohistological and molecular features, the latter ones defined after
      isolation of the different neoplastic areas by laser capture microdissection.
      RESULTS: Polymerase chain reaction assays revealed HHV8 DNA sequences only in the
      microdissected Kaposi's sarcoma areas and EBV DNA sequences only in the
      lymphomatous areas in both cases, confirming the HHV8 infection only in the
      neoplastic sarcomatous cells and evidencing the EBV infection only in the
      lymphomatous cells. CONCLUSION: This study represents a further confirmation of
      the supposed different etiopathogenic mechanisms of the 2 neoplasias, suggesting
      a coincidental occurrence even when localized in the same lymph node,
      independently from HIV infection.

PMID- 17505130
TI  - Pulmonary hypertension in sickle-cell disease: comorbidities and
      echocardiographic findings.
AB  - BACKGROUND: Our aim is to determine comorbidities associated with pulmonary
      hypertension (PHT) in clinically stable sickle-cell disease (SCD) patients and to
      evaluate left ventricular (LV) and right ventricular (RV) function in those
      patients. METHODS: Echocardiography was performed in 87 SCD patients that were
      divided into group I (without PHT) and group II (with PHT). Both groups were
      compared with healthy controls. RESULTS: A history of retinopathy and leg ulcer
      was more frequent in group II than group I (p < 0.01). Haemoglobin levels were
      lower (p < 0.05), whereas blood urea nitrogen, lactate dehydrogenase and total
      bilirubin levels were higher in group II (p < 0.01). Although group II patients
      had larger LV end-diastolic, LV end-systolic and RV diastolic diameters compared
      with group I patients and controls (p < 0.05), LV ejection fraction was similar
      in the three groups. The mitral peak early diastolic inflow velocity to peak late
      diastolic inflow velocity (E/A) ratio was similar in group I, group II and the
      control group. The tricuspid E/A ratio was lower in group II than group I and
      controls (p < 0.05). CONCLUSION: End organ damage occurs more often and
      haemolysis is severer in SCD patients with PHT than SCD patients without PHT.
      Although LV systolic and diastolic function is well preserved, RV diastolic
      function is disturbed in those patients with PHT.

PMID- 17505131
TI  - Is bone marrow biopsy obligatory in all patients with non-Hodgkin's lymphoma?
AB  - Bone marrow biopsy (BMB) is recommended as a part of the workup diagnosis in all
      patients with non-Hodgkin's lymphoma (NHL). This is an invasive procedure that is
      mostly stressful for the patient and very rarely is associated with severe
      bleeding. We suggest that the clinician needs to weigh up the potential benefit
      of this procedure in each case in terms of changing therapeutic approach and
      prognosis. We think BMB is not mandatory in every patient with NHL and suggest
      recommendations for which patients we should continue to perform this procedure
      on.

PMID- 17505132
TI  - Severe epidermal necrolysis after bortezomib treatment for multiple myeloma.

PMID- 17505133
TI  - Prevalence and determinants of coronary and aortic calcifications assessed by
      chest CT in renal transplant recipients.
AB  - BACKGROUND: Coronary artery calcifications independently predict cardiovascular
      events (CVE) in the general population. We assessed the prevalence and
      determinants of coronary (CAC) and thoracic aorta (AoC) calcifications in renal
      transplant recipients (RTR). METHODS: Consecutive RTR living in Belgium, with an
      isolated kidney graft functioning for more than 1 year, were asked to
      participate. They underwent a 16-slice spiral computerized tomography in order to
      measure calcium mass. Demographic, clinical, biochemical and urinary parameters
      were recorded. RESULTS: We included 281 patients. CAC and AoC were detected in 81
      and 85%, with geometric means (SD) of 52.2 (4.9) and 99.3 (8.2) mg, respectively.
      By multiple linear regression, independent predictors of both types of
      calcifications included older age, longer time on dialysis, a history of CVE, of
      multiple transplantations and of smoking. Other determinants of CAC were male
      gender, current statin use and history of parathyroidectomy, and other
      determinants of AoC included higher pulse pressure, shorter time under
      mycophenolate mofetil and current use of anti-vitamin-K. CONCLUSION: The
      prevalence of both CAC and AoC is substantial in RTR. We delineate independent
      determinants either common to both CAC and AoC or specific to one, and known as
      classic or chronic kidney disease related risk factors.

PMID- 17505134
TI  - Etho-archaeology of manual laterality: well digging by wild chimpanzees.
AB  - We present the first indirect test of manually lateralized behaviour in non-human
      primates, based on wells dug for drinking water by wild chimpanzees (Pan
      troglodytes schweinfurthii). Apes at Toro-Semliki Wildlife Reserve, in Uganda,
      dig bimanually in sandy riverbeds, leaving behind paired piles of excavated sand.
      The volumes of left- versus right-side piles do not differ, suggesting a lack of
      behavioural laterality, but this needs to be verified by further, direct
      observational data.

PMID- 17505135
TI  - True hermaphroditism in a phenotypic male without ambiguous genitalia: an unusual
      presentation at puberty.
AB  - True hermaphroditism usually appears with ambiguous genitalia requiring extensive
      evaluation during the neonatal period. There have been occasional cases with
      better differentiation of external genitalia, leading to delays in diagnosis. We
      report the case of an adolescent boy with true hermaphroditism who presented with
      normal external genitalia and no sexual ambiguity. He was referred due to
      progressive gynecomastia and arrest of puberty. He presented at the age of 16
      years for gynecomastia of rapid progression with normal penile development and
      both gonads in scrotum and normal testosterone and increased gonadotropin levels.
      Gonadal ultrasound scan was compatible with testicular and ovarian tissues in
      scrotum, and the karyotype showed two cellular lines (46,XX/46,XY). Gonadal
      histology revealed bilateral ovotestes. A genotype polymerase chain reaction
      mediated analysis using seven microsatellite markers did not confirm chimerism.
      Clinical findings and mechanism of generation are discussed.

PMID- 17505136
TI  - The International Study of Wheezing in Infants: questionnaire validation.
AB  - BACKGROUND: There are no internationally validated questionnaires to investigate
      the prevalence of infant wheezing. This study was undertaken to validate a
      questionnaire for the International Study on the Prevalence of Wheezing in
      Infants (Estudio Internacional de Sibilancias en Lactantes, EISL). MATERIAL AND
      METHODS: Construct and criterion validity were tested for the question 'Has your
      baby had wheezing or whistling in the chest during his/her first 12 months of
      life?'. Construct validity (i.e. the ability of parents and doctors to refer to
      the same symptoms with the same words) was tested in a sample of 50 wheezing and
      50 non-wheezy infants 12-15 months of age in each of 10 centres from 6 different
      Spanish- or Portuguese-speaking countries. Criterion validity (i.e. the ability
      of parents to correctly detect the symptom in the general population) was
      evaluated in 2 samples (Santiago, Chile and Cartagena, Spain) of 50 wheezing and
      50 non-wheezing infants (according to parents) of the same age, randomly selected
      from the general population, who were later blindly diagnosed by a paediatric
      pulmonologist. RESULTS: Construct validity was very high (kappa test: 0.98-1) in
      all centres. According to Youden's index, criterion validity was good both in
      Cartagena (75.5%) and in Santiago (67.0%). Adding questions about asthma
      medication did not improve diagnosis accuracy. CONCLUSIONS: The EISL
      questionnaire significantly distinguished wheezy infants from healthy ones. This
      questionnaire has a strong validity and can be employed in large international
      multicentre studies on wheezing during infancy.

PMID- 17505137
TI  - Hypersensitivity to paracetamol in Asian children with early onset of
      nonsteroidal anti-inflammatory drug allergy.
AB  - BACKGROUND: The published incidence of paracetamol cross-reactivity in adults and
      adolescents with nonsteroidal anti-inflammatory drug (NSAID) reactions is low and
      all data on such reactions in young children is sparse. The study aim was to
      characterize the clinical presentation and cross-reactivity with paracetamol in
      patients with a reported onset of NSAID hypersensitivity before 6 years of age.
      METHODS: A retrospective case review was done of patients with cross-reactive
      hypersensitivity reactions to antipyretic/analgesic medications from the
      pediatric allergy clinic of the Kendang Kerbau Hospital, Singapore. Included
      patients reported the onset of such reactions before 6 years of age.
      Hypersensitivity was established through a detailed history of recurrent
      reactions to NSAIDs or an oral provocation test. RESULTS: Eighteen patients
      fulfilled the diagnostic criteria within the study period. Eighty-three percent
      had cross-reactive reactions with paracetamol. When compared to the group of
      children with later onset of NSAID hypersensitivity, children with onset before 6
      years of age had a significantly increased likelihood of reacting to paracetamol
      (odds ratio 9.6, 95% confidence interval 1.6-58.0, p < 0.05). CONCLUSION:
      Paracetamol seems to be a major eliciting drug in this group of children.

PMID- 17505138
TI  - Detection of some safe plant-derived foods for LTP-allergic patients.
AB  - BACKGROUND: Lipid transfer protein (LTP) is a widely cross-reacting plant pan
      allergen. Adverse reactions to Rosaceae, tree nuts, peanut, beer, maize, mustard,
      asparagus, grapes, mulberry, cabbage, dates, orange, fig, kiwi, lupine, fennel,
      celery, tomato, eggplant, lettuce, chestnut and pineapple have been recorded.
      OBJECTIVE: To detect vegetable foods to be regarded as safe for LTP-allergic
      patients. METHODS: Tolerance/intolerance to a large spectrum of vegetable foods
      other than Rosaceae, tree nuts and peanut was assessed by interview in 49
      subjects monosensitized to LTP and in three distinct groups of controls
      monosensitized to Bet v 1 (n = 24) or Bet v 2 (n = 18), or sensitized to both LTP
      and birch pollen (n = 16), all with a history of vegetable food allergy. Patients
      and controls underwent skin prick test (SPT) with a large spectrum of vegetable
      foods. The absence of IgE reactivity to foods that were negative in both clinical
      history and SPT was confirmed by immunoblot analysis and their clinical tolerance
      was finally assessed by open oral challenge (50 g per food). RESULTS: All
      patients reported tolerance and showed negative SPT to carrot, potato, banana and
      melon; these foods scored positive in SPT and elicited clinical symptoms in a
      significant proportion of patients from all three control groups. All patients
      tolerated these four foods on oral challenge. Immunoblot analysis confirmed the
      lack of IgE reactivity to these foods by LTP-allergic patients. CONCLUSION:
      Carrot, potato, banana and melon seem safe for LTP-allergic patients. This
      finding may be helpful for a better management of allergy to LTP.

PMID- 17505139
TI  - Occupational allergy to latex among loom tuners in a textile factory.
AB  - BACKGROUND: Occupational allergy to latex is generally reported from occupational
      groups such as health care workers; however, few reports derive from other
      occupational settings. METHODS: Two male subjects working as loom tuners in a
      textile manufacturing plant developed severe allergic reactions during the
      cutting and weaving of elastic bands, initially not suspected to contain latex
      constituents. Clinical evaluation and lung function tests were supplemented by
      skin prick testing, specific IgE evaluation and basophil activation assays with
      extracted elastic bands. RESULTS: Both workers presented with rhinitis, episodes
      of tight chest and itchy eyes. Initial spirometry was normal with no significant
      reversibility; however, a histamine challenge test was positive in one worker.
      Skin prick testing to a battery of common inhalant allergens was negative;
      however, raised IgE levels were detected to latex using ImmunoCAP. On further
      testing, the specific IgE response was directed mainly to the major latex
      allergens rHev b 5, rHev b 6.01, rHev b 6.02 and nHev b 13. Basophils of the two
      workers, but not the unaffected control subjects, were strongly activated by
      extracts of the elastic and the cutting dust material. CONCLUSIONS: Workers are
      at high risk of becoming sensitised to latex allergens when exposed to excessive
      dust produced by loom tuning machines. Latex sensitisation should therefore be
      considered in workers developing unexplained work-related allergic reactions
      (including asthma) associated with unlabelled materials in the textile industry.

PMID- 17505140
TI  - Detection of Dermatophagoides farinae in the dust of air conditioning filters.
AB  - BACKGROUND: The allergenic dust mite species Dermatophagoides pteronyssinus and
      Dermatophagoides farinae generally inhabit warm moist environments. This study
      tested the hypothesis that these allergenic species may thrive in air conditioner
      filters. METHODS: A year-long investigation of the dust mite population densities
      and species identities living in air conditioner filters in Shenzhen City in
      Southern China was performed. Additional data describing the levels of major dust
      mite allergen proteins from samples collected in July and August 2004 were
      analyzed. Genetic polymorphism analysis of Der f 1 and Der f 2 genes in the
      collected animals was also conducted. RESULTS: Our investigation revealed that
      larval dust mites started to grow in March, from which time their populations
      proceeded to steadily increase until reaching their population zenith in July and
      August. The dust mite populations decreased sharply in October and live dust
      mites were no longer observed in the winter. Among the mites collected in July
      and August, 30.1 and 25.8% were of the species D. farinae. The concentration of
      Der f 1 was 3.04 +/- 1.75 and 3.21 +/- 1.84 microg/g dust in July and August,
      respectively, and that of Der f 2 was 2.15 +/- 0.82 and 2.04 +/- 1.15 microg/g
      dust. Four types of Der f 1 and 5 types of Der f 2 cDNA sequences were cloned
      from collected Der f mites. Their sequences were highly homologous with those
      previously published in GenBank (No. AB034946.1 and No. AB195580.1). CONCLUSIONS:
      This research demonstrated that Der f allergens exist in the dust of air
      conditioner filters in this area.

PMID- 17505141
TI  - Inductions of histidine decarboxylase in mouse tissues following systemic antigen
      challenge: contributions made by mast cells, non-mast cells and IL-1.
AB  - BACKGROUND: Previous findings suggest that antigen challenge (AC) may induce
      histidine decarboxylase (HDC) in cells other than mast cells (MCs) via MC-derived
      IL-1. We examined this hypothesis. METHODS: Mice were sensitized to ovalbumin.
      After the sensitization, an AC was delivered intravenously. RESULTS: In control
      mice, AC markedly induced HDC at a postanaphylactic time in the liver, lung,
      spleen, and ears. In MC-deficient W/W(v) mice, AC also induced HDC, although the
      effect was weaker than in control mice. AC increased IL-1 in the tissues, the
      pattern being similar in W/W(v) and control mice. AC induced HDC similarly in IL
      1-deficient and control mice. In control mice, AC decreased histamine in the
      tissues (except the liver) for several hours. CONCLUSION: (1) AC induces HDC in
      both MC-dependent and MC-independent ways. (2) AC induces IL-1 mostly in non-MCs,
      but this IL-1 is not a prerequisite for the induction of HDC by AC. (3) HDC
      induction may contribute to the replenishment of the reduced pool of MC histamine
      in the anaphylactic period. (4) In the case of MC-dependent HDC induction, AC may
      stimulate MCs in such a way as to induce HDC within the MCs themselves, and/or AC
      stimulated MCs may stimulate HDC induction in other cells, which will need to be
      directly identified in future studies.

PMID- 17505142
TI  - Endogenous interleukin-10 produced by antigen-irrelevant cells promotes the
      development of experimental murine allergic conjunctivitis.
AB  - Interleukin (IL)-10 is known to act as an immunoregulatory cytokine in both T
      helper cell 1 (Th1)- and Th2-mediated immune responses. Here, we ask whether IL
      10 regulates the development of experimental allergic conjunctivitis (EC), a Th2
      mediated inflammatory disease. Wild-type (WT) and IL-10 knockout (IL-10 KO) mice
      were immunized with ragweed (RW) and then repeatedly challenged with RW in eye
      drops. Twenty-four hours after the final challenge, conjunctivas were harvested
      for histological analysis, while the blood and spleens were used to determine the
      RW-specific immunoglobulin levels in serum and proliferation or cytokine
      responses and splenocyte transfer, respectively. The IL-10 KO mice had
      significantly less severe EC (as determined by conjunctival eosinophil
      infiltration) than the WT mice and evinced greater RW-specific splenocyte
      proliferation and cytokine production. However, the RW-specific immunoglobulin
      levels of the two strains did not differ. When the splenocytes from RW-primed WT
      mice were transferred into IL-10 KO or WT mice, the IL-10 KO mice showed
      significantly less conjunctival eosinophil infiltration. In contrast, when the
      splenocytes from RW-primed IL-10 KO or WT mice were transferred into WT mice,
      both splenocyte populations generated equivalent severe EC. These data indicate
      that IL-10 does not serve as an immunoregulatory cytokine in the development of
      EC. Instead, it appears that IL-10 produced by antigen-irrelevant cells acts in
      the effector phase to promote the development of EC.

PMID- 17505143
TI  - CX3CR1 polymorphisms are associated with atopy but not asthma in German children.
AB  - Chemokines and their receptors are involved in many aspects of immunity.
      Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration
      and macrophage differentiation as well as T cell-dependent inflammation. Two
      common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter
      the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk
      for asthma. Using matrix-assisted laser desorption/ionization time-of-flight
      technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross
      sectional population of German children from Munich (n = 1,159) and Dresden (n =
      1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63-0.96; p =
      0.017) and for 280Met an odds ratio of 0.71 (95% confidence interval 0.56-0.89; p
      = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism
      was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the
      development of atopy but not asthma in German children. Potentially, other
      factors such as environmental effects may modify the role of CX3CR1
      polymorphisms.

PMID- 17505144
TI  - Upregulation of CD4+ NKT cells is important for allograft survival in
      staphylococcal-enterotoxin-B-treated rats after high-risk corneal
      transplantation.
AB  - OBJECTIVE: To study the role of CD4+ natural killer T (NKT) cells in
      staphylococcal-enterotoxin-B (SEB)-treated rats after high-risk corneal
      transplantation. METHOD: Fisher 344 donor corneas were transplanted into Lewis
      recipients. Corneal neovascularization was induced by sutures. All the recipients
      were randomly divided into 3 groups. The SEB group was intraperitoneally injected
      with SEB at a concentration of 75 microg/kg. The drug combination group received
      SEB and dexamethasone at a concentration of 5 mg/ml. The control group received
      saline buffer. All transplants were evaluated for 30 days. Ten days after
      transplantation, 3 recipients in each group were sacrificed for immunological
      study. RESULT: The survival time of the allografts in the SEB group was 12.50 +/-
      1.41 days, much longer than in the control group (7.30 +/- 0.67 days) and the
      drug combination group (10.38 +/- 3.07 days). The lymphocyte proliferation
      ability was the weakest and the percentage of CD4+ NKT cells in both the spleen
      and the mandibular lymph nodes was the highest in the SEB group, while the
      percentage of CD4+ and CD8+ cells was the lowest in the drug combination group.
      IL-2 in the aqueous humor and the serum was lower while IL-10 was higher in the
      SEB group than in the other 2 groups. CONCLUSION: SEB prolongs allograft survival
      in rat high-risk corneal transplantation. This effect seems to be mediated by the
      upregulation of CD4+ NKT cells.

PMID- 17505145
TI  - Vascular endothelial growth factor and basic fibroblast growth factor in
      exudative age-related macular degeneration and diffuse diabetic macular edema.
AB  - BACKGROUND: To evaluate the concentrations of vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF) in neovascular or edematous
      retinal diseases. METHODS: In the clinical comparative interventional study, VEGF
      and bFGF concentrations in aqueous humor samples of 35 patients with exudative
      age-related macular degeneration (AMD), 21 patients with diabetic macular edema
      and 24 patients of a control group were measured using a solid-phase
      chemiluminescence immunoassay. RESULTS: Concentrations of VEGF and bFGF,
      respectively, were significantly higher in the diabetic group (184.7 +/- 107.0
      and 5.0 +/- 10.2 pg/l) than in the AMD group (107.7 +/- 73.0 pg/l, p = 0.002; 2.2
      +/- 7.4 pg/l, p = 0.002) and the control group (71.5 +/- 94.7 pg/l, p = 0.001;
      0.00 pg/l, p = 0.001). The two latter groups did not vary significantly (p =
      0.10). CONCLUSIONS: VEGF and bFGF are present in considerably higher
      concentrations in eyes with diabetic macular edema than in eyes with exudative
      AMD or normal eyes. The differences were more marked for VEGF than for bFGF.

PMID- 17505146
TI  - Increased osteopontin levels in the vitreous of patients with diabetic
      retinopathy.
AB  - PURPOSE: Osteopontin (OPN) has diverse functions such as cell adhesion,
      chemoattraction, immunomodulation, and angiogenesis. The aim of this study is to
      analyze the OPN levels in vitreous fluid obtained from diabetic retinopathy (DR)
      and non-DR patients. METHODS: Nineteen patients out of 11 with DR and 8 without
      DR underwent pars plana vitrectomy and vitreous fluid was obtained
      simultaneously. Two distinct sandwich enzyme-linked immunosorbent assay systems
      (systems 1 and 2) were applied, which have been developed in our laboratories to
      quantify the OPN concentrations in vitreous fluid. RESULTS: The non-thrombin
      cleaved full-length OPN levels in the vitreous fluid were 921.63 +/- 45.38 ng/ml
      in DR and 632.80 +/- 83.43 ng/ml in non-DR using system 1. Also, vitreous
      thrombin-cleaved and noncleaved OPN levels were increased to 2,109.22 +/- 151.651
      and 1,651.13 +/- 229.82 ng/ml in patients with DR and non-DR using system 2. The
      vitreous OPN levels were significantly higher in DR than those in non-DR (p <
      0.01 by system 1 and p < 0.05 by system 2). CONCLUSION: Thrombin-cleaved and
      noncleaved vitreous OPN levels in patients with DR were increased compared with
      control subjects, suggesting that OPN plays a potential role in the pathogenesis
      of diabetic retinal ischemia.

PMID- 17505147
TI  - Postjunctional synergism of norepinephrine with ATP and diadenosine
      tetraphosphate in Guinea pig vas deferens. Role of protein kinase C and Myosin
      light chain phosphatase.
AB  - In isolated guinea pig vas deferens, prior addition of norepinephrine (NE)
      significantly potentiated the contractile responses to adenosine-5'-triphosphate
      (ATP) and diadenosine tetraphosphate (AP4A) in a dose-dependent manner up to 240%
      of the control purine dose. The myosin light chain phosphatase (MLCP) inhibitor
      cantharidin at a dose of 10 micromol/l caused significant enhancement of ATP at
      concentrations of 1 and 3 mmol/l by 91 and 95% respectively. Similarly,
      cantharidin enhanced the contraction to AP4A, 30 and 100 micromol/l by 92 and
      100% respectively. Inhibition of protein kinase C (PKC) by the use of
      chelerythrine (10 micromol/l), incubated at the vas deferens for 60 min,
      inhibited the NE-induced enhancement of purine-induced contraction. Chelerythrine
      reversed the NE-ATP and NE-AP4A synergism back close to control ATP and AP4A
      contraction values respectively. It can be concluded that postjunctional
      synergism becomes evident not only for adenine mononucleotides and NE but also
      for diadenosine polyphosphates presented here by AP4A in the guinea pig vas
      deferens. This synergism involves receptor-mediated activation of PKC and
      possibly PKC-induced inhibition of MLCP.

PMID- 17505148
TI  - Possible reasons for different pattern disappearance of thyroglobulin and thyroid
      peroxidase autoantibodies in patients with differentiated thyroid carcinoma
      following total thyroidectomy and iodine-131 ablation.
AB  - The purpose of this study was to reveal some possible factors for the differences
      between the pattern of disappearance of thyroglobulin autoantibodies (anti-Tg)
      and thyroid peroxidase autoantibodies (anti-TPO) in patients with differentiated
      thyroid carcinoma following thyroidectomy and iodine-131 ablation. Patients with
      a history of follicular cell derived cancer (papillary, follicular, both
      papillary and follicular, Hurthle cell) and high pre-operative titers of anti-TPO
      and/or anti-Tg autoantibodies were retrospectively studied. Thyroglobulin (Tg)
      levels were measured using radio-immunometric assay (RIA). Anti-Tg and anti-TPO
      levels during the first 6 yr' follow-up were measured by passive agglutination,
      during the following 10 yr by ELISA method and during the last 2 yr by
      chemiluminescence assay. A statistically significant difference was observed
      between median time (72 months) of disappearance of anti-TPO and median time (39
      months) of disappearance of anti-Tg in patients with complete ablation of thyroid
      tissue, following iodine-131 administration (p=0.0395, Logrank statistic=4.24,
      Kaplan-Meier method). A statistically significant difference was observed between
      median time (106 months) of disappearance of anti-TPO and median time (33 months)
      of disappearance of anti-Tg in patients >45 yr of age (p=0.034) and between
      median time (111 months) of disappearance of anti-TPO and median time (41 months)
      of disappearance of anti-Tg in patients with tumor size <2 cm (p=0.0175). We
      concluded that patients with differentiated thyroid carcinoma and pre-surgical
      elevated titers of both Tg and anti-TPO tend to become earlier anti-Tg
      seronegative. Although tumor size and age may influence the pattern of thyroid
      autoantibody reduction, the exact reasons for the different rhythm of
      autoantibodies decrease must further be evaluated.

PMID- 17505149
TI  - In Sicilian ethnic group non-classical congenital adrenal hyperplasia is
      frequently associated with a very mild genotype.
AB  - The spectrum of mutated alleles in non-classical congenital adrenal hyperplasia
      (NC-CAH) has been recently reported to be very large and haplotypes may
      significantly differ in the different ethnic groups. In order to confirm that
      population differences may exist in the genetic basis of this disease, we have
      analyzed the genetic presentation of NC-CAH in a Sicilian cohort of symptomatic
      patients and compared our findings with the ones reported in other studies of
      different ethnic groups. In 38 NC-CAH patients coming from two regions of Sicily
      and born of Sicilian parents, we found that 84.2% of the chromosomes examined
      bore only mild mutations and only the remaining 15.8% of the chromosomes bore at
      least 1 severe mutation. The overall predominant mutation was V281L, which was
      detected in 73.7% of alleles and in 89.5% of patients. About 58% of the patients
      were homozygotes for this mutation. V281L allele and homozygote frequencies were
      higher in the present series than in other European and Italian reports. In our
      NC-CAH population, which is one of the largest ever reported, the patients with
      two mild mutations exhibited a less severe impairment of both clinical and
      endocrine phenotype. On the basis of these results we can conclude that: a) in
      Sicilian ethnic groups NC-CAH is frequently associated with a very mild genotype;
      b) the most frequent genotype in our series is V281L homozygosis; c) clinical and
      biochemical expression of NC-CAH is more marked in the patients bearing a severe
      mutation; d) no correlations between genotype and phenotype were found in our
      patients affected by NC-CAH.

PMID- 17505150
TI  - Asymmetric dimethylarginine levels in thyroid diseases.
AB  - Thyroid diseases may lead to endothelial dysfunction; however, the mechanism
      underlying the endothelial dysfunction in thyroid disease is not clear yet.
      Asymmetric dimethylarginine (ADMA), a novel inhibitor of endothelial nitric oxide
      synthase (eNOS), blocks nitric oxide (NO) synthesis from L-arginine. Symmetric
      dimethylarginine (SDMA) is the structural isomer of the eNOS inhibitor ADMA. SDMA
      does not directly inhibit eNOS but is a competitive inhibitor of arginine
      transport. Increased plasma ADMA, SDMA concentrations, and low L-arginine/ADMA
      ratio were considered as possible contributing factors for endothelial
      dysfunction in hyperthyroid patients. On the other hand, plasma ADMA, SDMA levels
      and L-arginine/ADMA ratio in the hypothyroid group were unexpectedly found to be
      similar to those of the control subjects. The aim of this study is to evaluate
      and compare the plasma ADMA levels in hyperthyroid, hypothyroid and healthy
      subjects. Plasma ADMA, SDMA, and L-arginine levels were measured by high
      performance liquid chromatography. Plasma ADMA levels were significantly higher
      in both patients with hyperthyroidism and hypothyroidism than in the control
      group. SDMA concentrations were significantly increased in hypothyroid patients
      compared to control subjects. Patients with hyperthyroidism and hypothyroidism
      had significantly higher plasma L-arginine levels compared with healthy controls.
      L-arginine/ADMA ratio, which shows NO bioavailability, was significantly lower in
      hyperthyroid patients than in both hypothyroid and control subjects. In
      hyperthyroidism, plasma ADMA levels were related to age, L-arginine, and SDMA
      levels. SDMA was associated with age and L-arginine. L-arginine/ADMA ratio was
      negatively associated with freeT4 levels. There was a relationship between ADMA
      and L-arginine in hypothyroid patients. SDMA was significantly related to L
      arginine, total cholesterol, and LDL. In conclusion, not only hyperthyroidism but
      also hypothyroidism was associated with alterations of ADMA and SDMA metabolism.

PMID- 17505151
TI  - Control of fatty acid metabolism by leptin in L6 rat myoblasts is regulated by
      hyperinsulinemia.
AB  - The development of hypothalamic leptin resistance plays a role in the development
      of obesity, yet whether peripheral leptin resistance occurs in obesity and
      diabetes is controversial. Here we investigate whether hyperinsulinemia, as
      observed during the development of Type 2 diabetes, modifies the effects of
      leptin on long chain fatty acid metabolism in skeletal muscle cells. We used
      boron dipyrromethene difluoride (BODIPY)-labeled palmitate to show that leptin
      (60 nM) caused a time-dependent (0-60 min) increase in fatty acid uptake in L6
      myoblasts. Quantitative analysis using 3H-palmitate showed that pre-incubation
      with insulin (100 nM, 24 h) prevented stimulation of fatty acid uptake by leptin.
      Insulin pre-treatment also attenuated the ability of leptin to phosphorylate
      acetyl Co-A carboxylase and increase palmitate oxidation. Suppressor of cytokine
      3 (SOCS-3) has been proposed as a possible mediator of insulin-induced leptin
      resistance. Here we show that treatment of L6 cells with insulin elicited a time
      dependent increase in both SOCS-3 mRNA and protein content. In summary,
      hyperinsulinemia can induce leptin resistance in L6 myoblasts and this may be
      mediated via a SOCS-3-dependent mechanism.

PMID- 17505152
TI  - Adrenal incidentaloma: surgical update.
AB  - Nowadays, the role of surgery in the treatment of adrenal incidentalomas (AI),
      considering their biologic behavior, is still debated. Surgery is mandatory in
      cases of hyperfunctioning adrenal masses, in the presence of suspect radiological
      malignancy, in cases of discordant computed tomography (CT) and scintigraphy
      findings and when the maximum diameter is 4 cm or more. On the other hand,
      studies have suggested relative inaccuracy of conventional CT in evaluating the
      size. The aim of this paper was to evaluate the safety and effectiveness of
      laparoscopic adrenalectomy (LA) in the treatment of AI by reviewing our
      experience. Over the period from 1995 to 2005 we laparoscopically managed 78 AI
      by anterior transperitoneal approach. Two LA (2.6%) were converted to open
      surgery. Neither intra- nor post-operative major complications were observed. The
      mean size of lesions was 5.5 cm (range 3-9). Twenty-one large adrenal lesions
      (exceeding 6 cm) were removed (27%). Definitive histology resulted as follows:
      adrenocortical adenoma (63), pheochromocytoma (5), nodular hyperplasia (4),
      myelolipoma (3), cysts (2), and adrenocortical carcinoma (1, with a size of 3
      cm). The patients were followed-up by hormonal and radiological evaluation every
      12 months (6 for malignancy); their follow-up (median 60.4 months, range 6-123)
      was uneventful. Also larger AI were treated safely. Laparoscopy has been safe and
      effective in the treatment of AI in our experience, according to specific
      literature.

PMID- 17505153
TI  - Bone mineral content and bone mineral density at lumbar spine and forearm in
      Chinese girls aged 6-18 years.
AB  - We investigated the age-related bone mineral content (BMC), bone mineral density
      (BMD) and the tempo of growth in BMC and BMD at lumbar spine and forearm in 455
      Chinese girls aged 6-18 yr. BMC and BMD at the anteroposterior lumbar spine (LS),
      the left forearm (radius+ulna ultradistal, R+UUD) and one-third region (R+U1/3)
      were measured using a dual-energy X-ray bone densitometer (DXA). BMC and BMD
      exhibited different change patterns with the age changes. There were significant
      correlations between age, height, weight and BMC and BMD at LS, R+UUD and R+U1/3
      sites. BMC and BMD increased significantly with increments in pubertal stages at
      LS, R+UUD and R+U1/3 sites. In conclusion, our study showed that Tanner stage had
      a significant positive association with BMC and BMD of the lumbar spine and
      forearm. The differences were found in the growth tempo of BMC and BMD within a
      region and between the spine and forearm. Both BMD and BMC were recommended to
      evaluate the bone health in children and adolescents.

PMID- 17505154
TI  - The correlation between adiposity and adiponectin, tumor necrosis factor alpha,
      interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size
      associated with inflammation in adults?
AB  - OBJECTIVE: Hypertrophic obesity correlates with metabolic complications of
      obesity. We evaluated adipocyte volume and its relationship with tumor necrosis
      factor alpha (TNF-alpha), interleukin-6 (IL-6), adiponectin and high sensitivity
      C-reactive protein (hs-CRP) levels. SUBJECTS AND METHODS: Patients were divided
      into 4 groups; lean healthy controls [body mass index (BMI): 24.2+/-1.4 kg/m2],
      non-diabetic obese patients (30.2+/-2.9), obese (30.1+/-3.2) and non-obese
      (22.2+/-1.5) Type 2 diabetic patients. TNF-alpha, hs-CRP, adiponectin and IL-6
      levels were measured preoperatively and sc fat specimens were obtained during
      operation. Semi-thin sections were stained with toluidine-blue and evaluated by
      light microscopy. Fat volumes were calculated by Goldrick's formulation. RESULTS:
      Mean adipocyte volumes were higher in obese diabetic patients than in other
      groups (p<0.0001). Mean TNF-alpha, hs-CRP and IL-6 levels were higher in obese
      diabetic patients than in control subjects, obese non-diabetic and non-obese
      diabetic patients (p<0.0001, p<0.02 and p<0.01, respectively). Mean TNF-alpha
      levels of non-diabetic obese patients were higher than the control group
      (p<0.05). Mean IL-6 levels of diabetic and non-diabetic obese patients were
      higher than control subjects (p<0.02 and p<0.0001, respectively). Mean
      adiponectin levels of control subjects were higher than non-diabetic obese, non
      obese diabetic and obese-diabetic subjects (p<0.0001). Mean adiponectin levels of
      obese diabetic patients were lower than non-diabetic obese subjects (p<0.008).
      Mean hs-CRP levels were higher in diabetic patients whether they were obese or
      not. There was a positive correlation between adipocyte size and TNF-alpha
      (p<0.01), IL-6 (p<0.03) and hs-CRP levels (p<0.004), and negative correlation
      between adipocyte size, adiponectin levels (p<0.0001). CONCLUSIONS: TNF-alpha, IL
      6 and hs-CRP levels were positively, adiponectin negatively correlated with
      adipocyte size. Therefore, adiposity may be an inflammatory condition.

PMID- 17505155
TI  - Corticotroph axis sensitivity after exercise: comparison between elite athletes
      and sedentary subjects.
AB  - Strenuous exercise activates the hypothalamic-pituitary-adrenal (HPA) axis.
      Several reports showed that physical training is associated with a decreased
      efficiency of the feedback control of HPA axis. The aims of the present study
      were: 1) to evaluate the differences in the mechanical, hormonal, and lactate
      responses to a high-intensity isokinetic exercise among different groups of
      competitive athletes (CA, no.=20) of power and endurance disciplines and
      sedentary controls (SED, no.=10); 2) to determine the effects of the training
      status on the HPA axis responsiveness following exercise, as indirectly evaluated
      by the rates of ACTH, cortisol, and DHEA recovery after exercise. CA and SED
      fulfilled eight sets of twenty concentric contractions of the knee extensors at
      180 degrees/sec angular velocity throughout a constant range of motion (100
      degrees). There was a rest period of 30 sec between each set and a 3-min rest
      period between the two legs. Before, immediately after the isokinetic exercise
      and at different times in the subsequent 120 min of recovery, blood and saliva
      were sampled to determine plasma ACTH, salivary cortisol, serum DHEA, and serum
      lactate concentrations. CA showed a higher cortisol response to exercise than
      SED, whereas no differences were found in the responses of ACTH, DHEA and
      lactate. In the athlete group the exercise-induced increases of ACTH, cortisol,
      and lactate were higher in power athletes with respect to endurance athletes. No
      differences were observed between athletes and SED in the rates of hormonal
      recovery after exercise: this finding does not support the concept that a reduced
      feedback control of HPA axis can represent a feature of trained individuals.

PMID- 17505156
TI  - A single growth hormone determination 30 minutes after the administration of the
      GHRH plus GHRP-6 test is sufficient for the diagnosis of somatotrope dysfunction
      in patients who have suffered traumatic brain injury.
AB  - As hypopituitarism is frequent in patients who have suffered a traumatic brain
      injury (TBI) a hormonal check-up is necessary. However, the prevalence of TBI is
      so large that the number of potential candidates to be tested is difficult to
      manage, in particular for GH deficiency diagnosis that requires cumbersome and
      expensive dynamic tests. GHRH plus GH-releasing hexapeptide (GHRP-6) is a safe
      and effective test capable of segregating normal subjects from GH deficient
      patients. As the GHRH+GHRP-6 test induces GH peaks consistently in the first 30
      min, the working hypothesis assessed in this study was whether a single
      determination of GH 30 min after stimulus could provide the same biochemical
      classification as the whole secretory curve. A total of 83 subjects who suffered
      TBI at least one year before the study were administered GHRH 1 mug/kg iv plus
      GHRP-6 1 mug/kg iv at 0 min, and blood samples were obtained at regular
      intervals. GH was determined in all samples. An excellent correlation was
      observed between GH values at 30 min and GH peaks (r=0.972, p<0.0001). When
      comparing the 30-min GH values against the peaks, the biochemical classification
      changed only in 5 out of 83 subjects from normal GH secretion to uncertain.
      CONCLUSIONS: The GHRH+GHRP-6 test is convenient, safe and in patients with TBI
      can be reduced to a single fixed GH determination 30 min after stimulus without
      losing diagnostic power.

PMID- 17505157
TI  - Favorable clinical heart and bone effects of anti-thyroid drug therapy in
      endogenous subclinical hyperthyroidism.
AB  - Although subclinical hyperthyroidism (SCH) has been associated with increased
      risk of osteoporosis and cardiac arrhythmias, its treatment is still
      controversial. This study was designed as a prospective, randomized,
      intervention, control-study with a 1-year follow-up in order to investigate
      whether normalization of serum TSH in SCH using methimazole has favorable bone
      and heart clinical effects. Fourteen patients with endogenous SCH (not Graves'
      disease) were enrolled, 7 (5 women/2 men; group T) were treated with methimazole
      (2.5-7.5 mg/day), and 7 (5 women/2 men; group C) were followed without treatment;
      10 healthy subjects were also included in the study as controls. Serum free-T3
      (FT3), free-T4 (FT4) and TSH, thyroid echography, bone stiffness index (SI), as
      measured by heel ultrasonometry, and 24-h electrocardiography monitoring were
      obtained. SCH patients exhibited higher systolic and diastolic blood pressure
      than control subjects. They also had a significantly higher number of both
      ventricular premature beats (VPB) (mean+/-SEM: 681+/-238 vs 6+/-2 beats/24 h;
      p<0.02) and atrial premature beats (APB) (mean+/-SEM: 495+/-331 vs 7+/-2 beats/24
      h; p<0.0001), and a lower SI (66+/-5 vs 96+/-3; p<0.001). Twelve months after
      normalization of TSH with the use of methimazole, the number of VPB decreased
      significantly (947+/-443 vs 214+/-109 beats/24 h; p<0.05) while it remained
      unchanged in untreated SCH patients (414+/-163 vs 487+/-152 beats/24 h; p=ns). An
      insignificant therapy effect was observed as far as APB were concerned (826+/-660
      vs 144+/-75 beats/24 h; p=ns), however their number increased significantly in
      the untreated group (463+/-49 vs 215+/-46 beats/24 h; p<0.05). The SI increased
      significantly as a result of therapy in group T (64.1+/-4.8 vs 70.0+/-5.3;
      p<0.02) and was further reduced in group C at the end of the study (69.1+/-7.3 vs
      62.9+/-7.1; p<0.001). No adverse effect was observed in group T. In conclusion,
      anti-thyroid therapy seems to have favor-able bone and heart clinical effects in
      subjects with endogenous SCH.

PMID- 17505158
TI  - Insulin resistance in children with Helicobacter pylori infection.
AB  - We aimed at investigating insulin resistance in children with Helicobacter pylori
      (H. pylori) infection. Fasting serum insulin and glucose levels were determined
      in 31 children with H. pylori (+) (H. pylori-infected group, 20 girls and 11
      boys, median age 12 yr, range 6-17) and 29 H. pylori (-) (control group, 18 girls
      and 11 boys, median age 13 yr, range 5-16). Insulin resistance was assessed using
      homeostasis model assessment of insulin resistance (HOMA-IR) score. Fasting serum
      glucose levels did not differ significantly between H. pylori (+) and (-)
      children. Both HOMA-IR score and serum insulin levels were significantly higher
      in H. pylori-infected compared to control children. The findings of the present
      study suggested that there is a certain relation between H. pylori infection and
      insulin resistance in children.

PMID- 17505160
TI  - Pulmonary multinodular mucormycosis in type 1 diabetic patient with diabetic
      ketoacidosis.
AB  - We report a case of pulmonary multinodular mucormycosis in a Type 1 diabetic
      patient with diabetic ketoacidosis. He had a history of 20-pack-year tobacco use.
      The initial chest roentgenogram and thorax tomography (after the treatment of
      diabetic ketoacidosis) revealed multiple nodular lesions with cavitation in the
      upper lobes of pulmonary parenchyma. Resection of three nodular lesion
      demonstrated cheesy necrotic mass in the cavitating lesions. The diagnosis of
      pulmonary multinodular mucormycosis was made depending on the histopathologic
      examination yielding nonseptated right angle branching-shaped hyphae typical of
      mucormycosis. The patient was started on liposomal amphotericin B and discharged
      at the sixth week of therapy with a scheduled therapy of amphotericin B. When he
      came back after 33 months, he was metabolically unregulated under the insulin
      therapy. He confessed that he had been smoking heroin besides tobacco for the
      last 5 years. A new thorax computerized tomography showed that pulmonary nodules
      were slightly regressed but not resolved.

PMID- 17505159
TI  - Evaluation of IGF-I levels during long-term somatostatin analogs treatment in
      patients with gastroenteropancreatic endocrine tumors.
AB  - Previous experiments reported desensitization to SS action in rat anterior
      pituitary cells and cell lines. The aim of the study was to verify whether the
      lack of desensitization to SS analogs (SSa) observed in acromegalic patients was
      also present in subjects with normal hypothalamic-pituitary function. The effect
      of chronic treatment with octreotide long-acting release (o-LAR, 10-30 mg/28
      days) on IGF-I levels was then evaluated in 23 patients with
      gastroenteropancreatic (GEP) endocrine tumors (8 gastrinomas, 6 carcinoids, and 9
      functioning pancreatic tumors). Serum IGF-I, clinical symptoms, plasma
      chromogranin-A (CgA) and markers of hepatic synthesis were evaluated before and
      after a short-term period in all the patients (median 4.5 months), after a medium
      term period in 12 (median 18 months) and after a long-term follow-up period in 9
      of them (median 48 months). Mean IGF-I levels decreased from 17.3+/-7.0 to 12.8+/
      6.2 nmol/l in the short-term (p<0.005) being reduced from baseline concentrations
      in 87% and under the normal range for age in 35% of patients. Afterwards, they
      always remained stable both in the medium- and long-term periods, still being low
      in 3/12 and 2/9 patients, respectively. No alterations in biochemical markers of
      liver function were found either before or during therapy. No correlation between
      IGF-I levels, CgA concentrations and/or clinical definitive outcome was observed.
      In conclusion, the study demonstrated that: a) similarly to that observed in
      acromegalic patients, chronic o-LAR treatment did not induce desensitization of
      pituitary SS receptors (SSR) in humans with intact hypothalamic-pituitary axis,
      and b) in patients with GEP endocrine tumors, GH/IGF-I inhibition did not
      contribute to SSa efficacy.

PMID- 17505161
TI  - Outcome of pregnancy in a hypothyroid woman with resistance to thyroid hormone
      treated with triiodothyronine.
AB  - Epidemiological and research data have shown the significant role of maternal
      thyroid hormone in fetal neurologic development. It has been suggested that
      maternal hypothyroxinemia is potentially damaging for the neurodevelopment of the
      fetus, independently of T3 levels. We present a pregnant woman with resistance to
      thyroid hormone and iatrogenic hypothyroidism who was treated with
      triiodothyronine during the whole pregnancy. Even though maternal
      hypothyroxinemia was severe the children showed a normal neuropsychological
      development.

PMID- 17505162
TI  - Adrenal pseudocyst mimicking cancer: a case report.
AB  - Adrenal cysts are infrequently observed, since less than 500 cases have been
      reported in Western literature. Adrenal cysts are conventionally divided into
      four categories: epithelial, parasitic, endothelial, and hemorrhagic. They are
      characterized by different etiological and pathological features. Some authors
      suggest that endothelial and hemorrhagic cysts are related and may represent a
      spectrum of lesions. We report herein the case of an adrenal hemorrhagic
      pseudocyst that simulated adrenocortical cancer and argue on the clinical clues
      for a differential diagnosis with other adrenal tumors.

PMID- 17505163
TI  - Healing of chronic necrobiosis lipoidica lesions in a type 1 diabetic patient
      after pancreas-kidney transplantation: a case report.
AB  - Necrobiosis lipoidica (NL) is a degenerative disease of dermal connective tissue
      of unknown etiology characterized by erythematous plaques preferentially
      localized to distal extremities. Skin lesions show a chronic relapsing nature. NL
      is often associated with diabetes mellitus and satisfactory treatment options are
      lacking. We describe the spontaneous healing of NL lesions after pancreas and
      kidney transplantation in a Type 1 diabetic patient with chronic NL recalcitrant
      to a variety of standard treatments. The 31-yr-old male patient had experienced
      NL lesions for more than 15 yr; despite various systemic and topical treatments,
      the skin lesions had pregressively enlarged. Because of end-stage renal disease,
      a simultaneous pancreas and kidney transplantation was performed and
      immunosuppressive therapy with tacrolimus (TAC), mycophenolate mofetil (MMF), and
      prednisone was started. Pancreatic transplantation maintained satisfactory
      metabolic control with no need of exogenous insulin. After transplantation, skin
      lesions slowly healed without any specific treatment, leaving residual areas of
      fibrotic scars. A skin biopsy confirmed the absence of typical NL lymphocytic and
      histiocytic inflammatory response. Clinical remission of NL lesions may probably
      be explained by the concomitant effect of multiple-drug regimen for
      immunosuppression (TAC, MMF, and prednisone) and improved skin microcirculation
      secondary to the good metabolic control provided by pancreas transplantation.

PMID- 17505164
TI  - A novel heterozygous splice-site mutation of LEM domain-containing 3 in a
      Japanese kindred with Buschke-Ollendorff syndrome.

PMID- 17505165
TI  - Hyperglycemia correlates with outcomes in patients receiving total parenteral
      nutrition.
AB  - BACKGROUND: Hyperglycemia is associated with higher mortality rates after
      myocardial infarction, stroke, and in critically ill patients. This study was
      made to determine the associations between hyperglycemia and adverse outcomes in
      patients receiving total parenteral nutrition (TPN). METHODS: A retrospective
      cohort study included total 457 patients (age, 66.4 +/- 16.3 years) receiving TPN
      in 2004. The patients were divided by mean glucose level into quartiles: quartile
      1 (<114 mg/dL, Q1), quartile 2 (114 to 137 mg/dL, Q2), quartile 3 (137 to 180
      mg/dL, Q3), and quartile 4 (>180 mg/dL, Q4). A logistic regression analysis was
      performed to determine whether the degree of hyperglycemia was associated with
      the adverse outcomes. RESULTS: The odds ratio of death was significantly
      increased in quartile 2 (OR, 2.1 [95% CI: 1.1 to 4.0]) (P = 0.02), quartile 3
      (OR, 2.3 [95% CI: 1.2 to 4.5]) (P = 0.01), and quartile 4 (OR, 5.0 [95% CI: 2.4
      to 10.6]) (P < 0.01) as compared with quartile 1. Each 10-mg/dL increase in mean
      blood glucose level was associated with an increased risk factor of infection
      (OR, 1.09 [95% CI: 1.05 to 1.13]) (P < 0.01), cardiac complications (OR, 1.10
      [95% CI: 1.03 to 1.17]) (P < 0.01), acute renal failure (OR, 1.07 [95% CI: 1.03
      to 1.11]) (P < 0.01), and respiratory failure (OR, 1.08 [95% CI: 1.02 to 1.14])
      (P < 0.01). The risk of adverse outcomes increased with hyperglycemia,
      independent of age, sex, body weight, prior diagnosis of diabetes, ICU stay,
      insulin therapy, blood sugar readings before TPN treatment, and frequency of
      blood sugar measurements. CONCLUSIONS: Hyperglycemia in patients receiving TPN
      correlates with morbidities and mortality. A prospective, randomized, controlled
      study instituting aggressive hyperglycemic control is required to determine
      whether the control of blood glucose can improve outcomes in patients receiving
      TPN.

PMID- 17505166
TI  - Efficacy of rifaximin, a nonabsorbed oral antibiotic, in the treatment of small
      intestinal bacterial overgrowth.
AB  - INTRODUCTION: Rifamixin is an orally administrated, nonabsorbed antibiotic whose
      utility in eradication of small intestinal bacterial overgrowth (SIBO) is
      currently being evaluated. PURPOSE: The aim of this study was to investigate
      efficacy and safety of rifaximin in relieving symptoms and normalizing the
      glucose breath test (GBT) in patients with SIBO. METHODS: Symptom score
      assessment, consisting of frequency and severity of bloating, gas, abdominal
      pain, and bowel movements and the GBT were performed before and after treatment
      with rifaximin 800 mg/d for 4 weeks. SUBJECTS: Twenty consecutive symptomatic
      patients (16 women and 4 men; mean age, 47.8 years; range, 19 to 85 years) who
      had a positive GBT were prospectively studied in an open-labeled fashion.
      Fourteen patients (70.0%) presented with diarrhea, 3 (15.0%) with bloating and
      gas, and 3 (15.0%) with constipation as the dominant symptom. RESULTS: : Eleven
      patients were hydrogen producers, 8 exclusively methane, and 1 patient produced
      both gases by the GBT. Among patients with diarrhea, 12 of 14 (85.7%) reported
      improvement in symptom scores of more than 50%; 1 between 25% and 50%, 1 had no
      response after 4 weeks of rifamixin. Among patients with bloating and gas or
      constipation as the main symptom: 2 of 6 (33.3%) had improvement between 50% and
      75%; 3 (50%) had 25% to 50% improvement, and 1 (16.7%) had no response. Repeat
      GBT at the end of the 4 weeks showed that 54.5% of hydrogen formers and 50.0% of
      methane producers were eradicated, and there was a significant reduction (P
      <0.05) in the area under the concentration-time curve and peak values. No adverse
      effects were observed. CONCLUSIONS: Rifaximin in a dose of 800 mg per day for 4
      weeks: 1) was safe and effective treatment in reducing symptoms in patients with
      SIBO of multiple etiologies, especially when diarrhea was the dominant symptom;
      and 2) normalized the GBT in approximately 50% of patients. Data support a future
      therapeutic role for rifaximin in SIBO.

PMID- 17505167
TI  - Biochemical and virologic parameters in patients co-infected with hepatitis C and
      HIV versus patients with hepatitis C mono-infection.
AB  - BACKGROUND: Previous studies of patients with hepatitis C virus (HCV) infection
      looking at the effect of human immunodeficiency virus (HIV) co-infection on
      biochemical parameters and HCV RNA level have shown conflicting results. Accurate
      characterization of the effect of HIV is important for evaluation and treatment
      of HCV in co-infected persons. METHODS: We studied 315 HCV mono-infected and 75
      HCV-HIV co-infected subjects to determine the effect of HIV on biochemical
      parameters and HCV RNA and to determine the predictors of elevated serum alanine
      aminotransferase (ALT) levels and HCV RNA levels. RESULTS: The co-infected
      subjects were more likely to be African-American (55% vs 26%, P < 0.0005), have
      used injection drugs (68% vs 60%, P = 0.02), have detectable HCV RNA (84% vs
      70.5%, P = 0.018), have HCV RNA levels >6 log10 IU/mL (60% vs 38%, P = 0.001),
      and have lower mean serum ALT levels (50.4 IU/mL vs 73.7 IU/mL, P = 0.006). In
      multivariable analyses, the following factors predicted an ALT level >50 IU/mL:
      log10 HCV RNA (OR, 1.15; 95% CI, 1.00 to 1.32); HIV co-infection (OR, 0.48; 95%
      CI, 0.25 to 0.89); and having ever been treated for HCV (OR, 1.92; 95% CI, 1.16
      to 3.18). The only significant predictor of HCV RNA level >6 log10 IU/mL was HIV
      co-infection (OR, 2.75; 95% CI, 1.46 to 5.15). Significant predictors of having a
      detectable HCV RNA level were female sex (OR, 3.81; 95% CI, 1.18 to 12.25); HIV
      co-infection (2.45; 95% CI, 1.14 to 5.26); and ever being treated for HCV (OR,
      1.96; 95% CI, 1.10 to 3.48). CONCLUSIONS: HCV-HIV co-infected persons have higher
      HCV RNA levels but lower serum ALT levels than HCV mono-infected patients.
      Criteria for performing liver biopsy and treating HCV infection in co-infected
      patients may need to be revisited.

PMID- 17505168
TI  - Results of general internal medicine consultations for diabetes mellitus in 283
      cancer patients.
AB  - BACKGROUND: Diabetes is a major reason for patient referral to the General
      Internal Medicine (GIM) Department at M.D. Anderson Cancer Center. Previous
      studies of various factors that affect diabetes care have not focused on cancer
      patients. The objective of this study was to examine the level of diabetic care
      received by cancer patients. METHODS: We conducted a retrospective chart review
      of 283 consecutive GIM patients with diabetes in the years 2000 to 2001. For each
      patient, data were collected about the cancer, diabetes-related history, and the
      general internist's recommendations for further diabetes care. Patients were
      stratified by whether their cancer was controlled (stable or in remission) or
      uncontrolled (being actively treated by an oncologist or said to be progressive).
      chi tests and t tests were used to compare means for controlled cancer and
      uncontrolled cancer patient groups, with a value of P < 0.05 being considered
      significant. RESULTS: Patients with controlled cancer were more likely to have a
      lipid profile ordered (P < 0.001) or to be referred for diabetes-specific
      ophthalmology evaluation (P = 0.02). On logistic regression analysis, increasing
      patient age was associated with less frequent HgbA1c testing (P = 0.01), and both
      advanced age and uncontrolled cancer were associated with less lipid testing and
      ophthalmology referral. CONCLUSIONS: Patients with uncontrolled advanced cancer
      were not as aggressively treated for diabetes, especially if they were elderly.
      Further work should evaluate whether the observed level of diabetes care was
      appropriate and could affect patient outcome.

PMID- 17505169
TI  - The right subclavian vein can be used as a surrogate of the inferior vena cava,
      as an echocardiographic indicator of systemic venous congestion.
AB  - Respiratory variations in the caliber of the inferior vena cava, imaged in the
      subcostal view with the patient supine, correlated well with respiratory
      variation in the caliber of the right subclavian vein with the patient reclining
      at a 45 degrees angle. The subclavian vein was imaged by a right supraclavicular
      approach. We suggest that the right subclavian vein caliber be used as a
      surrogate of the inferior vena cava caliber when the latter cannot be used
      because of obesity, epigastric tenderness, or other reasons.

PMID- 17505170
TI  - Sealing the left atrial appendage: ready for prime time?
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia and a leading
      cause of stroke. Warfarin reduces the incidence of thromboemboli and is
      recommended for most patients with AF. However, oral anticoagulation is
      contraindicated or not tolerated by a significant percentage of patients with AF.
      Occlusion of the left atrial appendage, the major source of emboli in atrial
      fibrillation, has been shown to be a potential alternative to warfarin in
      patients with AF who have contraindications to anticoagulation. In this article,
      we describe the current percutaneous left atrial appendage occlusion devices,
      their safety in recent trials, and their potential role in stroke prevention in
      AF.

PMID- 17505171
TI  - Valproic acid-induced eosinophilic pleural effusion: a case report and review of
      the literature.
AB  - OBJECTIVE: To report a case of valproic acid-induced eosinophilic pleural
      effusion and to review the existing literature. CASE SUMMARY: A 25-year-old
      African-American man receiving valproic acid, 250 mg/d, had a moderate-sized
      right pleural effusion. Pleural fluid analysis revealed 75% eosinophils. The
      patient had no evidence of parasitic infection, hemothorax, or pneumothorax. One
      month after valproic acid was discontinued, there was no evidence of a pleural
      effusion by both chest radiography and thoracic ultrasonography. DISCUSSION:
      Valproic acid-induced pleural effusions have been reported in the medical
      literature in 5 case reports. Pleural fluid eosinophilia is almost always related
      to pneumothorax, hemothorax, parasitic infection, or drug toxicity; therefore,
      when the first 3 causes have been eliminated, a drug should be suspected. Only a
      few medications are known to cause pleural fluid eosinophilia, one being valproic
      acid. The Naranjo probability scale rated this adverse reaction as probably drug
      related. CONCLUSIONS: In all 6 patients discussed in this review, the pleural
      effusions resolved after discontinuation of the valproic acid. None of these
      patients had associated pulmonary infiltrates. Valproic acid eosinophilia may be
      associated with peripheral blood eosinophilia. Valproic acid should be added to
      the list of medications that can cause an eosinophilic pleural effusion.

PMID- 17505172
TI  - Metastatic angiosarcoma of the scalp causing Kasabach-Merritt syndrome.
AB  - We report a case of thrombocytopenia caused by Kasabach-Merritt syndrome (KMS) in
      a 69-year-old man with a metastatic angiosarcoma of the scalp. A review of the
      literature revealed that only 4 cases of KMS associated with angiosarcoma have
      been previously reported. All these cases occurred with a solitary large lesion.
      This is the first case of thrombocytopenia caused by KMS associated with small
      metastatic lesions of angiosarcoma that developed after the primary lesion has
      been completely removed.

PMID- 17505173
TI  - Reciprocal relation of thyroid-stimulating hormone and thyroid-stimulating
      immunoglobulin in a patient with endogenous subclinical hyperthyroidism.
AB  - A 72-year-old white woman with an abnormal serum thyroid-stimulating hormone
      (TSH) concentration was referred to our facility for a comprehensive evaluation.
      Circulating thyroxine (T4) and free thyroxine (FT4) concentrations were all in
      the normal range. Tri-iodothyronine (T3) concentrations were in the low end or
      slightly below the normal range. TSH was detectable but was below the limits of
      the normal range. The patient was clinically euthyroid and was receiving
      medication only for treatment of hypertension. The clinical and laboratory
      thyroid function status was consistent with a diagnosis of subclinical
      hyperthyroidism. The physical examination did not reveal thyroid enlargement, nor
      was there any evidence for the presence of thyroid nodules or ocular changes
      suggestive of Graves disease. Among thyroid autoantibodies of particular interest
      was the presence of a moderate thyroid-stimulating immunoglobulin (TSI) level
      that was stable and consistently present during a 7-month observational period.
      At 13 months after the initial visit, TSI antibodies were absent and TSH
      concentration had returned to the normal range. Based on the TSH agonist activity
      of TSI and the observed reciprocal relation of TSI and TSH, there was no need to
      suggest pituitary hypersensitivity to thyroid hormone.

PMID- 17505175
TI  - A variant of thyrotoxicosis associated with chronic thyroiditis characterized by
      prolonged fever, absence of anti-thyroidal antibodies, and favorable response to
      naproxen.
AB  - An unusual form of thyrotoxicosis due to chronic thyroiditis is described. A 78
      year-old debilitated woman was admitted because of fever to 38 degrees C
      persisting for the previous 16 months, for which the antipyretic effect of
      diclofenac sodium and pranoprofen had been insufficient or transient. Intense
      accumulation of gallium-67 citrate in the thyroid gland provided an initial clue
      to the diagnosis of masked thyrotoxicosis as a cause of the fever, and naproxen
      (300 mg/d) eliminated the fever and flaring of thyrotoxicosis. Despite the
      absence of autoantibodies related to chronic thyroiditis, needle biopsy revealed
      destructive thyroiditis due to chronic lymphocytic thyroiditis. This case
      suggests a previously unrecognized variant of thyrotoxicosis due to chronic
      thyroiditis, that is, neither painless thyroiditis nor acute exacerbation of
      Hashimoto thyroiditis, and instead characterized by prolonged fever, nontender
      thyroid, absence of antibodies associated with autoimmune thyroiditis, and
      excellent response to naproxen.

PMID- 17505174
TI  - Two giant renal aneurysms and renal arteriovenous fistula associated with cardiac
      insufficiency and a sustained elevation of atrial natriuretic peptide and brain
      natriuretic peptide.
AB  - A 64-year-old man presented with chief complaints of exertional dyspnea and
      palpitation. He had previously undergone left nephrolithotomies twice. A chest
      roentgenogram showed pleural effusion on both sides with cardiac dilation, and
      electrocardiography showed a frequent occurrence of ventricular premature
      contractions. An echocardiogram showed diffuse hypokinesis of the left
      ventricular wall motion (ejection fraction, 45%) and dilation of the left
      ventricle (left ventricular end-diastolic dimension, 61 mm). We administered
      diuretics, ACE inhibitors and a beta-adrenergic blocking agent after making a
      diagnosis of cardiac insufficiency. Because coronary angiography showed 90%
      stenosis of the left anterior descending coronary artery (No. 7), we performed
      coronary angioplasty in this locus. Though both the left ventricular wall motion
      and ejection fraction improved, and the clinical symptoms disappeared, the left
      ventricular end-diastolic dimension, and arrhythmia did not improve. Furthermore,
      the brain natriuretic peptide increased despite these treatments. Thereafter, a
      left renal artery aneurysm (extrarenal aneurysm measuring 5 cm in diameter and an
      intrarenal aneurysm measuring 3 cm in diameter) and a left renal arteriovenous
      fistula were discovered when abdominal echography was performed because of
      epigastric discomfort. As a result, a left total nephrectomy was performed.
      Subsequently, the left ventricular end-diastolic dimension and arrhythmia
      improved, and the brain natriuretic peptide returned to a normal value. We herein
      report a case that developed cardiac insufficiency due to a renal aneurysm and
      renal arteriovenous fistula after undergoing left nephrolithotomies twice.

PMID- 17505176
TI  - Autoimmune blistering disease in a patient with Graves disease and vitiligo.
AB  - Autoimmune thyroid diseases have been correlated with a variety of autoimmune
      diseases also affecting the skin. A 56-year-old patient with a history of
      vitiligo is presented who was admitted for hyperthyroidism (Graves disease) and a
      blistering eruption. Clinical and histological appearance of the skin disorder,
      rapid response to corticosteroids, recurrence and remission of the lesions with
      discontinuation and reintroduction of corticosteroids, respectively, were all
      suggestive of an autoimmune blistering disease accompanying autoimmune
      hyperthyroidism and vitiligo.

PMID- 17505177
TI  - Monoclonal gammopathy presenting as recurrent nephrotic syndrome: therapeutic
      implications.
AB  - Most forms of renal disease associated with monoclonal gammopathy result from
      deposition of monoclonal immunoglobulins or their subunits in different
      compartments of the kidney. Renal monoclonal immunoglobulin deposition disease
      (MIDD) is defined by linear deposits of monoclonal light-chain components in
      renal basement membranes, often producing a nodular sclerosing glomerulopathy.
      Clinical features of renal MIDD include proteinuria, with or without renal
      failure, and an association with dysproteinemias. Three types of renal MIDD have
      been reported, namely, light-chain deposition disease (LCDD), light- and heavy
      chain deposition disease (LHCDD), and heavy-chain deposition disease (HCDD).
      Reports on LHCDD are rare. At present, follow-up data are limited on the
      management of renal monoclonal protein deposition disease. We present a case of
      monoclonal protein deposition in the kidney containing both heavy and light
      chains with unique characteristics that did not conform to any of the above
      previous established classes. Its follow-up revealed an unusual relapsing and
      remitting course in response to treatment.

PMID- 17505178
TI  - Delayed manifestation and slow progression of cerebral infarction caused by
      polycythemia rubra vera.
AB  - BACKGROUND: Polycythemia rubra vera is often found after the manifestation of
      cerebral infarction, though the pathogenesis is still controversial. We present a
      case of cerebral infarction secondary to polycythemia rubra vera, which presented
      a slow expansion on magnetic resonance imaging despite severe hemiplegia. This
      case suggests a possible mechanism for development of cerebral infarction in
      polycythemia rubra vera. METHODS: This case report was conducted in a university
      hospital. Magnetic resonance imaging and diffusion-weighted imaging were
      performed to assess the evolution of infarction, and the total blood volume and
      cerebral blood flow were determined with the use of isotopes, Cr and Tc,
      respectively. Phlebotomy was performed, but intervention was not applicable. The
      manual muscle test and sensory disturbance were assessed by the same
      physiotherapist throughout the clinical course. RESULTS: A 64-year-old male
      patient with polycythemia rubra vera had a cerebral infarction. A subtle change
      was observed on CT scan on the third day after the onset of infarction, and a
      small signal was demonstrated on magnetic resonance imaging on the fourth day.
      The cerebral infarction expanded slowly in size and reached a maximum on day 24.
      A diagnosis of cerebral infarction secondary to polycythemia rubra vera was made,
      and treatment by phlebotomy, hydration, and hydroxyurea was begun. Though the
      hemiplegia remained, he became ambulatory with a brace, as do patients with
      atherosclerotic infarction. CONCLUSIONS: It is suggested that the delayed
      manifestation and slow expansion of cerebral infarction caused by elevated
      hematocrit might be derived from a pathogenesis different from atherosclerotic
      infarction.

PMID- 17505180
TI  - Violence and children: a view from the emergency department.

PMID- 17505181
TI  - Trends and challenges in international pediatric emergency medicine.
AB  - PURPOSE OF REVIEW: Pediatric emergency care internationally is practiced in a
      wide variety of local contexts, and the quality of care varies. International
      pediatric emergency medicine refers to the spectrum of care provided to children
      with serious illnesses and injuries globally. This article serves as the first of
      its kind to characterize current trends and challenges in this area. RECENT
      FINDINGS: Current trends in international pediatric emergency medicine include
      international dissemination of pediatric emergency medicine guidelines, pediatric
      specific disaster relief training, increasing numbers of pediatric emergency
      medicine research collaboratives, interest groups and training programs, and
      increasing numbers of spaces dedicated to pediatric emergency care. Current
      challenges to the field include inequalities in access to medical research and
      information, various nonmedical barriers and lack of reports describing
      approaches to the delivery of pediatric emergency care. SUMMARY: While there are
      many recent advances in the state of pediatric emergency medicine
      internationally, there still exist many barriers to the improvement in its
      quality. Many of these obstacles are not specific to pediatric emergency
      medicine, but reflect overall disparities between the developing and developed
      worlds. One first step to overcoming pediatric emergency medicine practiced in
      isolation is a formal organization of the field of international pediatric
      emergency medicine.

PMID- 17505182
TI  - The new American Heart Association cardiopulmonary resuscitation guidelines:
      should children and adults have to share?
AB  - PURPOSE OF REVIEW: The latest American Heart Association guidelines for pediatric
      cardiopulmonary resuscitation (CPR) were published in December 2005. Changes from
      the 2000 guidelines were directed toward simplifying CPR. Infants, children, and
      adults now share the same recommendation for the initial compression:ventilation
      ratio. This is a significant change for pediatricians trained in the importance
      of a respiratory etiology of pediatric cardiopulmonary arrest. The present review
      will focus on the rationale behind these guideline changes. RECENT FINDINGS: The
      new guidelines for single rescuer CPR include a compression:ventilation ratio of
      30: 2 for both adult and pediatric victims. The impetus for this recommendation
      is based on recent appreciation for the deleterious effects of hyperventilation
      as well as an attempt to increase bystander delivery of CPR. The physiologic
      results of hyperventilation are discussed. The new pediatric basic life support
      guideline changes are underscored. Research representing the spectrum of opinions
      on the optimal compression:ventilation ratio, including compression-only CPR, is
      presented. SUMMARY: Although based primarily on adult, animal, and computational
      models, the new compression:ventilation ratio, recommended for both initial
      pediatric and adult CPR, is a reasonable recommendation. The simplified CPR
      guidelines released in 2005 will hopefully contribute to improved bystander
      delivery of CPR and improved outcome.

PMID- 17505183
TI  - Controversies in the evaluation and management of minor blunt head trauma in
      children.
AB  - PURPOSE OF REVIEW: We present data from recently conducted research regarding
      controversial aspects of the evaluation and management of children with minor
      blunt head trauma. RECENT FINDINGS: Clinicians frequently but at times
      indiscriminately perform computed tomography scans for children with minor blunt
      head trauma resulting in potentially harmful radiation exposure. Recent
      guidelines recognize the limited but increasing data available to make strong
      recommendations regarding appropriate neuroimaging decisions. Investigators have
      derived and validated clinical prediction models to accurately identify patients
      with substantial traumatic brain injury, though no clear definitive rule exists.
      Children younger than 2 years appear to have a higher risk of intracranial injury
      following minor head trauma. These patients can be difficult to assess, with the
      evidence suggesting the need for a more conservative approach to diagnostic
      imaging. We present current and accepted definitions of concussion along with
      risk factors and treatment for postconcussion syndrome. Current return-to-play
      guidelines suggest that athletes who have sustained concussion should not resume
      play until symptoms have resolved because of the possibility, though rare, of
      second impact syndrome. SUMMARY: Research in the management of children with
      minor head trauma is actively evolving. We present a review of recent
      developments that can influence current clinical practice.

PMID- 17505184
TI  - Emergency department evaluation and management of blunt abdominal trauma in
      children.
AB  - PURPOSE OF REVIEW: To discuss the emergency department evaluation and management
      of children with blunt abdominal trauma. The review will focus on both the
      clinical data that can help reduce the use of computed tomography in the
      evaluation of patients with blunt abdominal trauma and the evidence for the
      increased use of nonoperative management of patients with blunt abdominal trauma.
      RECENT FINDINGS: We will examine the recent literature focusing on the utility of
      physical examination, laboratory data and imaging (both ultrasonography and
      computed tomography) in detecting intraabdominal injury. SUMMARY: Recent research
      suggests that physical examination in combination with bedside ultrasonography
      may identify children at risk for intraabdominal injury. Screening laboratory
      data appears to be less sensitive to detect these injuries, but is useful in
      selected patients. Nonoperative management is appropriate in a majority of cases.
      Further research is needed to determine which low-risk patients with abdominal
      trauma can be managed with minimal or no exposure to radiation in the computed
      tomography scanner.

PMID- 17505185
TI  - "Pharming": the abuse of prescription and over-the-counter drugs in teens.
AB  - PURPOSE OF REVIEW: Prescription and over-the-counter cough and cold medication
      abuse is rapidly becoming a national health concern for adolescents. Increased
      awareness of this growing epidemic is essential toward diagnosing, treating and
      preventing this type of substance abuse. RECENT FINDINGS: Data from surveys and
      poison control center records demonstrate an increased nonmedical use of
      prescription and over-the-counter cough and cold preparations, particularly those
      containing dextromethorphan. The nonmedical use of prescription medications may
      result in serious clinical effects with potential life-threatening complications,
      dependence and withdrawal syndromes. Dextromethorphan causes alterations in
      mental status that may contribute to judgment impairment leading to injury or
      fatality. Co-ingestion of other substances found in over-the-counter medications
      may also cause significant morbidity. Alcohol and illicit drug use is highly
      associated with the abuse of these medications. The incentive for abuse, such as
      easy accessibility, low cost and decreased perception of potential for harm, and
      potential interventions are described. SUMMARY: The recent trend of prescription
      and dextromethorphan-containing over-the-counter medication abuse in adolescents
      is alarming. Improved awareness for these readily available, seemingly benign yet
      highly dangerous medications is essential. Prevention and early education on
      substance abuse in young teens are critical in combating this recent epidemic.

PMID- 17505186
TI  - Lyme disease update.
AB  - PURPOSE OF REVIEW: Lyme disease is endemic to areas in both Europe and the United
      States and the incidence is increasing. Despite published guidelines, controversy
      persists about its diagnosis and management in patients who do not meet strict
      diagnostic criteria. This review summarizes important recently published studies
      and recommendations for the diagnosis and management of Lyme disease. RECENT
      FINDINGS: Recent comprehensive guidelines have been published for the diagnosis
      and management of pediatric Lyme disease. In addition, recent studies may help
      physicians differentiate between Lyme and aseptic meningitis, as well as show the
      poor sensitivity of cerebrospinal fluid polymerase chain reaction. Controversy
      continues about the diagnosis and management of "chronic Lyme disease", despite
      the current medical literature. Recently published studies in the US have also
      better described southern tick-associated rash illness, an entity that may
      present a similar clinical picture to Lyme disease. Guidelines have also been
      published on the management and diagnosis of other tick-borne illnesses often
      seen as co-infections with Lyme disease. Finally, case reports have been
      published describing new cardiac manifestations associated with Lyme disease.
      SUMMARY: Controversies persist about the diagnosis and management of Lyme
      disease. Recently published guidelines and primary research can aid clinicians in
      diagnosing Lyme properly.

PMID- 17505187
TI  - Status asthmaticus in children.
AB  - PURPOSE OF REVIEW: The prevalence of severe asthma in children has risen in the
      past few decades. The present review explores our current understanding of
      epidemiology, pathophysiology and treatment of status asthmaticus in children.
      RECENT FINDINGS: The pathophysiology of inflammation and airway hyperactivity
      continues to be a source of research. Early initiation of inhaled beta-agonists
      and oral or parenteral steroids remain the standard of care in the treatment of
      status asthmaticus. Other treatment modalities such as magnesium and intravenous
      beta-agonists show some benefit. There is a resurgence of interest in the use of
      methylxanthines. Alternatives to endotracheal intubation show some promise in
      preventing respiratory failure. SUMMARY: Asthma remains the third leading cause
      of hospitalization in children younger than 15 years old. Researchers continue to
      explore the efficacy of old and new treatment modalities. Future research efforts
      targeting at-risk populations could dramatically decrease asthma morbidity and
      mortality.

PMID- 17505188
TI  - An update on the approach to apparent life-threatening events.
AB  - PURPOSE OF REVIEW: Apparent life-threatening events are an ongoing diagnostic
      dilemma for clinicians. Since most apparent life-threatening event episodes occur
      in infants under 6 months of age, they can generate considerable anxiety in
      parents and providers. This review will discuss issues to consider in the
      evaluation of infants after an apparent life-threatening event. To ensure proper
      management, a systematic approach should be taken to attempt to determine the
      cause of the event. RECENT FINDINGS: More recent literature suggests that infants
      with apparent life-threatening events frequently present without signs or
      symptoms of illness. Obtaining a careful history and physical examination is
      essential in determining the cause of the event. In this article, we will review
      the most current literature and discuss the American Academy of Pediatrics new
      recommendations on sudden infant death syndrome prevention. SUMMARY: After a
      careful review of the literature, prone sleeping is one of the biggest risk
      factors for sudden infant death syndrome. The association between apparent life
      threatening events and sudden infant death syndrome remains to be explored
      further, but current evidence suggests minimal risk after an apparent life
      threatening event episode. This article will help clinicians prepare for this
      difficult challenge by providing up-to-date information and identifying problems
      to be addressed in future research.

PMID- 17505189
TI  - Age-related changes in the asthmatic phenotype in children.
AB  - PURPOSE OF REVIEW: To review the changes in the asthma phenotype as children
      progress from childhood into young adulthood. RECENT FINDINGS: Some children with
      asthma in the early school years improve symptomatically during adolescence and
      young adulthood, with less frequent remissions and increased relapse rates in
      those with severe symptoms. During remission of symptoms, lung function
      abnormalities, airway hyper-responsiveness, and airway inflammation often
      persist. New data from the Childhood Asthma Management Program cohort show
      progression of lung function abnormalities during adolescence. SUMMARY: Most
      children with persistent asthma have persistent disease as adults, and lung
      function abnormalities continue to progress as these children age.

PMID- 17505190
TI  - Steroid therapy for asthma in children.
AB  - PURPOSE OF REVIEW: To highlight studies that have contributed significantly to
      our current knowledge of inhaled glucocorticoids in childhood asthma. RECENT
      FINDINGS: In 2006, three important studies were published that investigated
      whether inhaled glucocorticoid therapy, if started soon after the onset of asthma
      symptoms, could alter the subsequent course of the disease. Several studies
      focused on the comparative clinical efficacy of inhaled glucocorticoids to
      leukotriene receptor antagonists in children with mild to moderate asthma.
      Although the Expert Panel had recommended inhaled glucocorticoid therapy as the
      preferred long-term controller with persistent asthma, there were no specific
      studies comparing these two classes of long-term controller medications in
      children. Another topic of significant clinical interest was the comparative
      efficacy of inhaled glucocorticoid to systemic glucocorticoids in the treatment
      of acute asthma. The question was answered in a study published in children with
      mild to moderate acute asthma. Lastly, the safety of inhaled glucocorticoid
      therapy was also evaluated in preschool children. SUMMARY: Inhaled
      glucocorticoids are the preferred long-term controller for initiating treatment
      of persistent asthma. Early intervention with inhaled glucocorticoids achieves
      symptom control but does not alter the natural history of asthma. Inhaled
      glucocorticoids are not as effective as systemic glucocorticoids for managing
      acute asthma exacerbations.

PMID- 17505191
TI  - New concepts in childhood tuberculosis.
AB  - PURPOSE OF REVIEW: Childhood tuberculosis has long been neglected in
      international tuberculosis control efforts. There are, however, many
      opportunities to prevent childhood tuberculosis that are not being fully
      employed. RECENT FINDINGS: Several papers have been published to emphasize the
      unique nature of childhood tuberculosis and improve tuberculosis control in
      children. Treatment regimens have been improved and refined. Clinical and
      radiographic methods have been standardized. While new diagnostic tests are
      greatly needed, it is also apparent that any new tests--such as the interferon
      release assays--will need to be studied specifically in infants and children or
      there is a risk they may be misapplied. The areas of greatest need for research
      and clinical utility remain better diagnostic tests for tuberculosis infection
      and disease; shorter and more effective regimens for treating tuberculosis
      infection; better integration of children into standard tuberculosis control
      practices; a better understanding of the interaction of human immunodeficiency
      virus infection and tuberculosis in children; detection and treatment of drug
      resistant tuberculosis in children; and a more effective vaccine. SUMMARY: True
      progress will require a rethinking of basic tuberculosis control with a
      commitment to address problems specific to childhood tuberculosis.

PMID- 17505192
TI  - Diffuse alveolar hemorrhage syndromes in children.
AB  - PURPOSE OF REVIEW: In this review we discuss the changing concepts of diffuse
      alveolar hemorrhage in children in terms of an expanded differential diagnosis
      and new approaches to diagnosis and treatment. RECENT FINDINGS: More commonly
      found in adults, pulmonary capillaritis, an immune-mediated form of diffuse
      alveolar hemorrhage often associated with systemic disease, has been recently
      reported in children. In a series of eight children with pulmonary capillaritis,
      serology for immune-mediated disorders was positive in only half. Acute
      idiopathic pulmonary hemorrhage is a unique condition of infants who present with
      acute pulmonary hemorrhage and respiratory failure. The hypothesis that acute
      idiopathic pulmonary hemorrhage is caused by toxigenic mold has not been proven,
      and its cause remains uncertain. SUMMARY: Classification of diffuse alveolar
      hemorrhage in children has been revised to include those conditions with and
      without pulmonary capillaritis. As idiopathic pulmonary hemosiderosis, the
      classic form of diffuse alveolar hemorrhage in children, is a diagnosis of
      exclusion and children with pulmonary capillaritis may have negative serology,
      lung biopsy should be strongly considered in any child with diffuse alveolar
      hemorrhage without a cardiovascular cause. Generally, patients with immune
      mediated lung disease require more aggressive pharmacologic intervention.

PMID- 17505193
TI  - Posttransplant monitoring of pediatric lung transplant recipients.
AB  - PURPOSE OF REVIEW: This article reviews current trends in pediatric lung
      posttransplant management, reveals pitfalls that exist, and introduces additional
      parameters that may have an impact on long-term survival. RECENT FINDINGS: A
      number of parameters are monitored after transplantation to prevent or identify
      early complications related to lung transplantation in hope of reducing morbidity
      and mortality. These include routine laboratory studies, imaging, and monitoring
      of drug levels and lung function. Drug monitoring allows individualization of a
      patient's immunosuppressive therapy; however, drug levels alone may not reflect
      the patient's immune status. ImmuKnow is a general immune-monitoring assay that
      may help guide therapy. Two major complications are rejection and infection, and
      bronchoscopy is used to differentiate these two entities. Silent rejection may
      occur and increase the chance of developing bronchiolitis obliterans; therefore,
      many centers perform surveillance bronchoscopies. Recently, de-novo anti
      histocompatibility locus antigen antibodies and gastroesophageal reflux have been
      associated with poor outcomes, and many centers are monitoring these entities as
      part of care following lung transplant. SUMMARY: There has been little
      improvement in long-term outcomes of lung transplantation. Current monitoring
      methods are utilized to maintain or improve outcomes and recently additional
      monitoring parameters have been identified which hopefully will improve long-term
      outcomes.

PMID- 17505195
TI  - Thoracic empyema, application of video-assisted thoracic surgery and its current
      management.
AB  - PURPOSE OF REVIEW: Pneumonia in children is frequently complicated by pleural
      effusions, which rarely progress to empyema. Appropriate clinical management
      depends on correctly diagnosing the stage of the disease process. Recently,
      increasing use of video-assisted thoracic debridement has altered the traditional
      management of pleural effusions and empyema in children, resulting in decreasing
      reliance on thoracentesis and earlier surgical intervention. RECENT FINDINGS: We
      review the current literature supporting the clinical indications for video
      assisted thoracic debridement compared with traditional management, including the
      use of thoracentesis, chest tube placement, fibrinolytic therapy and open
      thoracotomy in children with empyema. Recent studies support the early
      application of video-assisted thoracic debridement in children with empyema
      compared with traditional therapy, as it decreases the number of procedures and
      studies performed and the duration of chest tube drainage and is associated with
      less pain and shorter recovery period than open thoracotomy. SUMMARY: We propose
      a clinical algorithm supporting the early use of video-assisted thoracic
      debridement in the management of empyema in children.

PMID- 17505196
TI  - Gastrointestinal tract feeding access and the role of fundoplication in
      combination with gastrostomy.
AB  - PURPOSE OF REVIEW: Feeding access and associated antireflux procedures continue
      to be some of the most common operations performed in pediatric patients. This
      review will discuss the various feeding access procedures available, including
      minimally invasive techniques, and further elaborate on appropriate indications
      for a concurrent antireflux procedure as well as alternatives to fundoplication.
      RECENT FINDINGS: Gastrostomy and jejunostomy can be successfully placed using
      endoscopic or laparoscopic techniques with low complication rates. Nissen
      fundoplication is well described laparoscopically but failure with recurrent
      gastroesophageal reflux has resulted in the development of other operative
      alternatives. SUMMARY: Decisions concerning appropriate long-term feeding access
      must be individualized, understanding the advantages and disadvantages of
      gastrostomy and jejunostomy techniques. Laparoscopic Nissen fundoplication is
      successful for treatment of patients who fail medical therapy of gastroesophageal
      reflux, but recurrent gastroesophageal reflux is a persistent problem that
      requires innovative solutions.

PMID- 17505197
TI  - Minimally invasive surgery in the diagnosis and treatment of abdominal pain in
      children.
AB  - PURPOSE OF REVIEW: Children with abdominal pain sometimes require surgical
      intervention, and laparoscopy is increasingly the preferred approach for the
      diagnosis and treatment of both acute and chronic abdominal pain in children.
      This review describes the current state of the art and recent developments in the
      application of minimally invasive surgical techniques for the treatment of
      children with various abdominal pain syndromes. RECENT FINDINGS: Laparoscopy
      provides distinct advantages over traditional open surgery, including less pain,
      shorter recovery and improved cosmesis. Cumulative experience and ongoing
      outcomes research continue to substantiate the safety and efficacy of the
      approach when applied thoughtfully and by experienced practitioners. In fact, as
      minimally invasive surgery is being applied to treat more wide-ranging disorders,
      it is becoming apparent that for many conditions laparoscopy should be adopted as
      the standard of care. SUMMARY: Recent advances in minimally invasive surgery have
      clearly benefited children with abdominal pain who need surgery, and as
      techniques improve and instruments get smaller we can expect this trend to
      continue into the future.

PMID- 17505198
TI  - Inguinal hernia: what we have learned from laparoscopic evaluation of the
      contralateral side.
AB  - PURPOSE OF REVIEW: The evaluation for and management of a contralateral patent
      processus vaginalis in children presenting with a unilateral inguinal hernia has
      been debated for over 60 years. The emergence of transinguinal laparoscopy as an
      evaluative tool has changed the landscape of the debate, offering a safe and
      minimally invasive option. The review will highlight some of the significant
      recent contributions to this debate. RECENT FINDINGS: Recent studies have
      confirmed the safety of transinguinal laparoscopy, and demonstrated a high level
      of sensitivity and specificity for it in the evaluation of the contralateral
      inguinal ring. In comparison, the practice of physical examination under
      anesthesia for evaluation of the contralateral inguinal region has proven to be
      ineffective. Further, age and gender differences in the incidence of
      contralateral patent processus vaginalis have recently been challenged. These
      data call into question the practices of routine or selective open inguinal
      exploration and present laparoscopy as the most effective means of evaluation.
      SUMMARY: Transinguinal laparoscopy offers a safe and effective means of
      evaluating the contralateral inguinal ring during ipsilateral hernia repair. The
      relatively high incidences of both contralateral patent processus vaginalis and
      contralateral metachronous hernia development in children justify the use of
      routine laparoscopic evaluation.

PMID- 17505199
TI  - The use of laparoscopy in the management of nonpalpable undescended testes.
AB  - PURPOSE OF REVIEW: The stable incidence of undescended nonpalpable testes and the
      ever-progressing utilization of laparoscopy has led to the commonplace
      utilization of laparoscopy in the diagnosis and treatment of these nonpalpable
      testes. The historical published literature is ambiguous with regard to
      recommendations regarding the use of laparoscopy in the setting of nonpalpable
      testes. As a result, this review is timely and necessary in that it is important
      for the practicing physician and surgeon to review and have available to them the
      current recommendations for the management of patients with nonpalpable testes.
      RECENT FINDINGS: With ongoing advances of minimally invasive surgery in the face
      of the limitations of both ultrasound and magnetic resonance imaging, the use of
      laparoscopy in the diagnosis and treatment of nonpalpable testes is now
      commonplace. Several reports recommend laparoscopy as the gold standard for the
      evaluation and treatment of nonpalpable testes, allowing for localization of the
      testis, characterization of the testis and associated structures (vas deferens,
      testicular vessels) and subsequent treatment options. SUMMARY: Because of the
      superior diagnostic capabilities and the ability to provide therapeutic
      interventions, laparoscopy should be used in the evaluation and treatment of all
      patients with nonpalpable testes.

PMID- 17505200
TI  - Obesity prevention and the primary care pediatrician's office.
AB  - PURPOSE OF REVIEW: The obesity epidemic confronts the pediatrician every day in
      the office. Pediatricians should help curb the epidemic through prevention and
      the usual pediatric primary care tasks of screening, communication and
      anticipatory counseling. This review highlights findings from recent literature
      to guide office-based prevention of obesity in children. RECENT FINDINGS: More
      and more, children and society feel the effects of the obesity epidemic;
      prevention efforts need to begin earlier. Pediatricians' efforts to screen help
      identify at-risk children who may benefit from early lifestyle changes. The
      identification of overweight children also helps foster the appropriate work up
      of comorbidities. Pediatricians' communication of weight trajectories, which
      includes techniques like motivational interviewing, may help parents to adopt
      behavioral prescriptions. Pediatricians should focus on promoting breastfeeding,
      limiting television, increasing physical activity and reducing sugar-sweetened
      beverages. New tools used in the training setting show promising results.
      SUMMARY: Pediatricians must focus efforts on preventing childhood overweight,
      while awaiting effective treatment options for this chronic illness with its many
      associated morbidities. Such prevention involves sensitively communicating early
      body mass index screening results to parents and helping them to adopt key
      behavioral changes in diet and physical activity.

PMID- 17505201
TI  - Bibliography. Current world literature. Emergency and critical care pediatrics.

PMID- 17505202
TI  - Providers' knowledge of genetics: A survey of 5915 individuals and families with
      genetic conditions.
AB  - PURPOSE: Individuals affected by genetic conditions are increasingly likely to
      seek information about inheritance and risk factors from their primary care
      physicians rather than a geneticist, but several studies suggest that few health
      care providers are capable of fulfilling that role or are comfortable doing so.
      Acknowledging that the adoption of new genetics knowledge and technologies is
      often patient-driven, we asked affected individuals and family members about
      their experiences in encounters with a variety of nongenetics-trained health care
      providers. METHODS: Staff at the National Coalition for Health Professional
      Education in Genetics, the Genetic Alliance, and a University of Maryland
      graduate student in genetic counseling drafted a web-based survey. We recruited
      study participants from the Genetic Alliance, and a total of 5915 respondents
      completed the questionnaire between December 2004 and August 2005. RESULTS:
      Overall, 64% of respondents reported receiving no genetics education materials
      from the provider type named most important in the management of the condition in
      the family. We present knowledge ratings for various provider types and themes
      emerging from written descriptions of positive and disappointing experiences.
      CONCLUSION: We discuss the implications of these and other results for continuing
      genetics education and for clinical practice.

PMID- 17505203
TI  - Genetic testing in autism: how much is enough?
AB  - PURPOSE: To evaluate the yield of genetic testing in children with autism
      spectrum disorders. METHODS: We performed a retrospective chart review of 71
      unrelated patients with a diagnosis of an isolated autism spectrum disorder seen
      in a genetics clinic over a period of 14 months. For most, referrals occurred
      after evaluation by a developmental pediatrician and/or psychologist to establish
      the diagnosis. Tiered laboratory testing for the majority of the patients
      followed a guideline that was developed in collaboration with clinicians at The
      Autism Center at Children's Hospital, Columbus, OH. RESULTS: The patients
      included 57 males and 14 females; 57 met DSM-IV criteria for autism, with the
      rest being Asperger or pervasive developmental disorder not otherwise specified.
      Macrocephaly [head circumference (HC) >or=95%] was present in 19 (27%). Two
      children had visible chromosome abnormalities (47,XYY; 48,XY + 2mar/49,XY +
      3mar). Two patients with autism and macrocephaly had heterozygous mutations in
      the PTEN tumor suppressor gene. Three females had Rett syndrome, each confirmed
      by DNA sequencing of the MECP2 gene. Extensive metabolic testing produced no
      positive results, nor did fragile X DNA testing. CONCLUSION: The overall
      diagnostic yield was 10% (7/71). PTEN gene sequencing should be considered in any
      child with macrocephaly and autism or developmental delay. Metabolic screening
      may not be warranted in autism spectrum disorders without more specific
      indications or additional findings.

PMID- 17505204
TI  - Selection of family members for communication of cancer risk and barriers to this
      communication before and after genetic cancer risk assessment.
AB  - PURPOSE: The impact of genetic cancer risk assessment on communication of cancer
      risk information within families is not fully known. We compared women's
      selection of family members for cancer risk communication and perceived barriers
      to this communication before genetic cancer risk assessment and 6 months
      afterward. METHODS: Mailed surveys were used to collect prospective data from
      consenting women undergoing genetic cancer risk assessment because of a personal
      and/or family history of breast or ovarian cancers. Analysis included descriptive
      statistics, chi-square and McNemar tests, and paired t tests. RESULTS: A total of
      122 women met the study criteria. Although risk communications increased with
      first-degree relatives (84%-90% for females; 53%-62% for males) and decreased
      with non-first-degree relatives (21%-9%) before and after genetic cancer risk
      assessment, the degree of change was nonsignificant. The most commonly cited
      communication barrier was loss of contact (30%). Demographics, personal or family
      cancer history, and BRCA status did not significantly influence findings.
      CONCLUSIONS: There was a high degree of cancer risk communications with female
      first-degree relatives, but less so with male first-degree relatives, both before
      and after genetic cancer risk assessment. For the majority of women,
      interpersonal barriers did not preclude risk discussions. Further research is
      needed to identify how best to facilitate risk communication.

PMID- 17505205
TI  - The prevalence of the 235delC GJB2 mutation in a Chinese deaf population.
AB  - PURPOSE: Mutations in the GJB2 gene are the most frequently found mutations in
      patients with nonsyndromic hearing impairment in populations studied to date.
      However, the prevalence of mutations varies among different ethnic groups. In
      most areas of China, genetic testing for nonsyndromic hearing impairment is
      currently not available because of the lack of information regarding the
      molecular cause of nonsyndromic hearing impairment. The purpose of this study is
      to determine the prevalence of a common GJB2 mutation, 235delC, in Chinese deaf
      children. METHODS: We collected DNA specimens from 3004 patients with
      nonsyndromic hearing impairment from 26 regions of China; 368 Han Chinese and 98
      Uigur controls, and screened for the 235delC mutation. The coding exon of the
      GJB2 gene was polymerase chain reaction amplified, followed by restriction enzyme
      digestion with ApaI and analysis by agarose gel. RESULTS: Overall, 488 patients
      (16.3%) were determined to carry at least one 235delC mutant allele, with 233
      (7.8%) homozygotes and 255 (8.5%) heterozygotes. Therefore, within the
      subpopulations examined, the frequency varies from 0% to 14.7% for 235delC
      homozygotes and from 1.7% to 16.1% for heterozygotes. On the basis of this survey
      of the patient cohort as stated, Chinese patients with nonsyndromic hearing
      impairment appear to have a relatively higher 235delC frequency than that of
      other Asian populations. CONCLUSION: These results demonstrate that an easy and
      fast genetic testing method for this well-known GJB2 gene mutation can be made
      available for at least 2 million Chinese patients and family members with
      nonsyndromic hearing impairment. By screening for the common GJB2 235delC
      mutation, the molecular cause in as high as 15% of patients with nonsyndromic
      hearing impairment in certain regions of China can be identified. In addition,
      patients who are negative for the 235delC mutation would be candidates for
      further mutational analysis of GJB2 or other deafness-related genes.

PMID- 17505206
TI  - The impact of predictive genetic testing for hereditary nonpolyposis colorectal
      cancer: three years after testing.
AB  - BACKGROUND: To fully assess predictive genetic testing programs, it is important
      to assess outcomes over periods of time longer than the 1-year follow-up reported
      in the literature. METHODS: We conducted a 3-year study of individuals who
      received predictive genetic test results for previously identified familial
      mutations in Australian Familial Cancer Clinics. Questionnaires were sent before
      attendance at the familial cancer clinic and 2 weeks, 4 months, 1 year, and 3
      years after receiving test results. Psychological measures were included each
      time, and preventive behaviors were assessed at baseline and 1 and 3 years.
      Psychological measures were adjusted for age, gender, and baseline score.
      RESULTS: The study included 19 carriers and 54 non-carriers. We previously
      reported an increase in mean cancer-specific distress in carriers at 2 weeks with
      a return to baseline levels by 12 months. This level was maintained until 3
      years. Non-carriers showed sustained decreases after testing with a significantly
      lower level at 3 years compared with baseline (P < 0.001). These scores tended to
      be lower than those for carriers at 3 years (P = 0.09). Mean depression and
      anxiety scores did not differ between carriers and non-carriers and, at 3 years,
      were similar to baseline. All carriers and 7% of non-carriers had had a
      colonoscopy by 3 years, and 69% of 13 female carriers had undergone gynecological
      screening in the previous 2 years. Prophylactic surgery was rare. CONCLUSION:
      This report of long-term data indicates appropriate screening and improved
      psychological measures for non-carriers with no evidence of undue psychological
      distress in carriers of hereditary nonpolyposis colorectal cancer mutations.

PMID- 17505207
TI  - Renal anomalies in families of individuals with congenital solitary kidney.
AB  - PURPOSE: Congenital solitary kidney affects 1 in 1000 persons, whereas bilateral
      renal agenesis affects 1 in 5000. Because congenital solitary kidney is increased
      in parents of infants with bilateral renal agenesis and fetuses with renal
      anomalies on ultrasound, offspring of patients with congenital solitary kidney
      may be at risk of both unilateral and bilateral renal anomalies. The goal was to
      establish empiric risk estimates for counseling individuals with congenital
      solitary kidney. METHODS: Through a computerized review of records, subjects with
      congenital solitary kidney (defined as presumably congenital absence or severely
      reduced function of one kidney) were identified and asked to complete a
      questionnaire regarding urogenital anomalies in relatives. RESULTS: Empiric risks
      of 7% for offspring, 4% for parents, and 2.5% for siblings are minimal because
      not all relatives underwent ultrasound studies. The incidence of bilateral renal
      agenesis in offspring of congenital solitary kidney probands is 0.8%, which is
      much greater than the population risk but less than that for families with
      previous bilateral renal agenesis. Concordance for type of anomaly in affected
      relatives is only 50%, suggesting that various anomalies included in congenital
      solitary kidney (agenesis, dysplasia, cystic dysplasia) may overlap. Horseshoe
      kidney has 80% concordance and may be a separate autosomal dominant condition.
      CONCLUSION: Offspring and other relatives of individuals with congenital solitary
      kidney have significantly increased renal disease. Ultrasound is recommended for
      first-degree relatives, including fetuses at risk.

PMID- 17505208
TI  - Health beliefs among African American women regarding genetic testing and
      counseling for sickle cell disease.
AB  - PURPOSE: The Health Belief Model can help in understanding low acceptance of
      disease prevention and screening. We studied health beliefs of African American
      women to determine causes of low acceptance of genetic testing and counseling
      despite high prevalence of sickle cell disease and heterozygotes in this
      population. METHODS: An anonymous questionnaire using a 12-question measure with
      a 5-point Likert scale response was administered to 101 African American women
      attending an obstetrics and gynecology clinic to determine knowledge of sickle
      cell disease, perception of risk, severity, likelihood of benefit and barriers to
      counseling. RESULTS: The cumulative mean perceived scores on the 5-point Likert
      scale were 4.22 +/- 0.88 for severity of sickle cell disease, 4.10 +/- 1.03 for
      benefit of genetic testing, 2.28 +/- 1.00 for barriers to testing, and 2.62 +/-
      1.06 for risk of having a child with sickle cell disease. High average level
      knowledge was associated with high perception of severity and benefit to
      screening (P < 0.05). CONCLUSION: African American women have a relatively high
      belief of the severity of sickle cell disease and benefits of genetic counseling
      but frequently do not appear to believe that they are at risk of having a child
      with the disease. This should be taken into account in the design of educational
      and counseling strategies.

PMID- 17505209
TI  - Psychological adjustment among partners of women at high risk of developing
      breast/ovarian cancer.
AB  - PURPOSE: The aim of the current research was to characterize psychological
      adjustment among partners of women at high risk of developing breast/ovarian
      cancer and to explore the relationship between women's and partners' adjustment.
      METHODS: A study of 95 unaffected at-risk women and 95 partners was carried out
      using mailed, self-administered questionnaires with validated measures of
      psychological outcome. RESULTS: Elevated levels of distress were noted in up to
      10% of partners. High monitoring coping style and greater perceived breast cancer
      risk for their wife were associated with higher distress levels for partners.
      However, communicating openly with their wife and the occurrence of a recent
      cancer-related event in the woman's family were related to lower distress for
      partners. Partners' cancer-specific distress was positively related to their
      wives' distress. CONCLUSION: Among partners with elevated levels of distress, the
      ability to provide effective support to the at-risk women and participate
      appropriately in their decision making may be compromised. These partners are
      likely to benefit from targeted clinical interventions designed to reduce their
      distress levels. The findings emphasize the importance of considering partners of
      at-risk women in service provision and highlight the need for partners to obtain
      information and support specifically tailored to their needs.

PMID- 17505210
TI  - The three C's of administering chemotherapy: considerations, classifications,
      complications.

PMID- 17505211
TI  - Advocate for better funding of federal nursing programs.

PMID- 17505214
TI  - IV P.U.M.P. (politically useful messages for practicing nurses): healthcare an
      issue for presidential candidates in 2008.

PMID- 17505215
TI  - Infusion nursing standards of practice.

PMID- 17505216
TI  - The impact of infusion reactions on oncology patients and clinicians in the
      inpatient and outpatient practice settings: oncology nurses' perspectives.
AB  - Cancer patients treated with parenteral chimeric or humanized monoclonal antibody
      agents or chemotherapy are at risk of experiencing an infusion reaction. The
      impact of infusion reactions can be substantial. Infusion reactions, even when
      mild, can be disruptive and stressful. In-person interviews with 202 nurses were
      conducted at the 2005 Annual Oncology Nursing Society Congress to evaluate the
      impact of infusion reactions on patients and nurses in the inpatient and
      outpatient practice settings. Results from this survey study suggest that
      infusion reactions have a significant negative impact on both patients and
      nurses.

PMID- 17505217
TI  - Pericardial tamponade in patients with central venous catheters.
AB  - Cardiac (pericardial) tamponade occurs when the pressure of the fluid within the
      pericardial sac is high enough to impair the venous return to the heart. Cardiac
      tamponade can occur during central venous catheter placements. Nursing members of
      a central vascular catheter placement team benefit from quickly recognizing this
      clinical situation and understanding the appropriate clinical response. A
      methodical approach to this potentially fatal condition can greatly increase
      patient safety. This article reviews this condition, its clinical presentation
      and diagnosis, and strategies for avoiding central vascular access-associated
      tamponade.

PMID- 17505218
TI  - Managing hematologic toxicities in the oncology patient.
AB  - Myelosuppression associated with antineoplastic therapy may lead to neutropenia,
      anemia, or both, resulting in an increased risk for infection, fatigue,
      diminished quality of life, and reduced survival. Neutropenia can result in dose
      reductions and treatment delays. Hematopoietic growth factors have been used
      effectively as supportive therapy to reduce antineoplastic therapy-associated
      neutropenia and anemia. This article discusses management of neutropenia and
      anemia secondary to antineoplastic therapy, new medications, and nursing
      considerations.

PMID- 17505219
TI  - Vaccines: an innovative approach to treating cancer.
AB  - Recent scientific advances have expanded our understanding of the immune system
      and its response to malignant cells. Clinical trials are under way that attempt
      to translate this knowledge into effective cancer therapies. Vaccine therapy, an
      innovative approach to cancer treatment, attempts to activate the immune system
      to recognize cancer cells and eliminate them from the body. Preventive vaccines
      that already have been approved will have an impact on the incidence of certain
      cancers, and research is ongoing into treatment vaccines for various cancers.

PMID- 17505222
TI  - Intermittent auscultation of the fetal heartbeat: can nurses change the culture
      of technology?

PMID- 17505223
TI  - Implementation of interventions that support sleep in the NICU.

PMID- 17505224
TI  - Best practices in perinatal nursing: improving outcomes for obese and morbidly
      obese women during the intrapartum and postpartum periods.

PMID- 17505225
TI  - Biorhythms in the nursery.

PMID- 17505226
TI  - Sleep and pregnancy/postpartum.

PMID- 17505227
TI  - Sleep loss and fatigue in healthcare professionals.
AB  - Sleep loss and impairments related to resultant fatigue are common among
      professionals working in healthcare settings. Long continuous duty hours, reduced
      opportunities for sleep with minimal recuperation time, and shift work all
      contribute significantly to impairments in physical, cognitive, and emotional
      functioning. Detrimental effects include those on personal health and well-being,
      patient health and safety, performance of job-related tasks, and professionalism.
      Many challenges exist to implementing effective personal and systemwide
      strategies to manage the impact of sleep loss. Therefore, adopting fatigue
      management strategies that have been successful in other occupational settings
      and developing specific interventions that are appropriate for the hospital
      setting are key. The following review outlines the causes and consequences of
      sleep loss and fatigue in healthcare professionals, and provides an empirically
      based framework for developing strategies to recognize, address, and manage sleep
      loss and fatigue.

PMID- 17505229
TI  - Sleep disturbance in late pregnancy and early labor.
AB  - Sleep disturbance is a typical complaint during pregnancy, particularly in the
      third trimester. Previous studies of this phenomenon have not measured sleep in
      the last days of pregnancy as women transition into labor. Poor sleep can have
      potentially adverse effects on labor and delivery. OBJECTIVE: The purpose of this
      study was to evaluate the amount of sleep obtained in the 5 days preceding
      childbirth, and the relationship between sleep in this time frame and both pain
      and fatigue during early labor. METHODS: Thirty-five nulliparous women were
      recruited from childbirth preparation classes. Sleep was measured with wrist
      actigraphy continuously until hospital admission for delivery. Participants
      completed self-report measures of pain and fatigue in early labor prior to
      hospital admission. RESULT AND DISCUSSION: Most women experienced spontaneous
      labor onset during the night. Sleep quality deteriorated progressively over the
      last 5 days of pregnancy, and was the lowest on the night before hospital
      admission. This was the case even when labor was induced (40%). CONCLUSION: There
      was a significant relationship between the amount of sleep the night before
      hospitalization and pain perception in women with spontaneous labor onset.
      Results from this study can be used to advise women in late pregnancy about
      expected sleep patterns and measures to optimize sleep and rest.

PMID- 17505230
TI  - Early postpartum sleep and fatigue for mothers after cesarean delivery compared
      with vaginal delivery: an exploratory study.
AB  - OBJECTIVE: The purpose of this study was to describe sleep and fatigue during the
      first week of postpartum recovery, and compare women after cesarean delivery with
      women after vaginal delivery while their infants were hospitalized in the
      intensive care unit (ICU). METHODS: This cross-sectional descriptive exploratory
      study involved 21 postpartum Chinese American mothers (6 after cesarean delivery
      and 15 after vaginal delivery). Three types of data were collected: (1) mothers'
      demographic data; (2) objective sleep that included total sleep time (TST) and
      wake after sleep onset (WASO) measured using wrist actigraphy, and (3) subjective
      sleep quality (General Sleep Disturbance Scale) and fatigue severity (Numerical
      Rating Scale-Fatigue). RESULTS: All of the mothers experienced poor sleep while
      their 3- to 5-day-old infants were in the ICU. After cesarean birth, mothers
      averaged only about 4 hours TST with 34% WASO while still hospitalized, compared
      with 6.5 hours TST with 14% WASO for mothers after vaginal birth monitored in
      their home after hospital discharge. CONCLUSION: Sleep disturbances and fatigue
      need to be further investigated to better understand the relationship between
      type of delivery and maternal health outcomes. Despite infant care provided in
      ICUs, these new mothers could benefit from interventions to promote their own
      sleep, particularly when also recovering from cesarean delivery.

PMID- 17505231
TI  - Negotiating sleep: a qualitative study of new mothers.
AB  - OBJECTIVE: The purpose of this qualitative study was to learn from 20 mothers
      about their experience of sleep during pregnancy and the immediate months of
      becoming a new mother. The study was part of a larger randomized clinical trial
      on an intervention to improve sleep and well-being among new mothers. METHODS:
      Semistructured, audiotaped interviews were conducted in which women were asked to
      describe the continuum of the sleep experience across the pregnancy and early
      postpartum and to describe strategies they found helpful as they established
      sleep patterns with their infant. Narrative analysis was used to interpret their
      stories, and data were managed with Atlas.ti qualitative software. RESULTS AND
      CONCLUSIONS: Sleep disturbances were common to all of the mothers, and sleep
      became a negotiated behavior as they adjusted to the mothering role. All of the
      mothers were surprised at the level of disturbance and exhaustion they
      experienced. Strategies included enlistment of partners to facilitate naps,
      development of a "sleep consciousness," and bed-sharing. Mercer's stages of
      becoming a mother are used to describe the process of incorporating sleep changes
      into their lives.

PMID- 17505232
TI  - Patterns of sleep disruption and depressive symptoms in new mothers.
AB  - OBJECTIVES: This study describes the patterns of sleep disturbance and depressive
      symptoms in a sample of childbearing women from the third trimester through the
      postpartum period. The relationship between sleep and depressive symptoms is also
      examined. A secondary aim of this study was to examine the relationship between
      self-report measures of sleep and depressive symptoms between women with
      depressive symptoms in comparison with women with minimal or no depressive
      symptoms in the third trimester and in the third month postpartum. METHODS: This
      longitudinal, descriptive study followed 124 primiparous women from their last
      month of pregnancy through 3 months postpartum. Questionnaires on sleep and
      depressive symptoms were completed during the third trimester (Time 1), 1 month
      postpartum (Time 2), 2 months postpartum (Time 3), and during the third month
      postpartum (Time 4). Sleep measures in a subset of women with depressive symptoms
      were compared with those of women with minimal or no symptoms at Time 1 and Time
      4. RESULTS AND CONCLUSIONS: Sleep disturbance and depressive symptoms were
      associated at Time 1 and Time 4. For new mothers, a complaint of trouble falling
      asleep (delayed sleep onset latency) may be the most relevant screening question
      in relation to their risk for postpartum depression.

PMID- 17505233
TI  - State systems development in high-risk newborns in the neonatal intensive care
      unit: identification and management of sleep, alertness, and crying.
AB  - The state system is a fundamental component of newborn neurodevelopmental
      function and demonstrates the newborn's underlying neurologic and behavioral
      competence. The role of the state system in newborn developmental assessment
      reflects the newborn's ability to respond to the environment. This overview
      examines the importance of the state system as a significant developmental
      process, identifies specific variations in sleep and wakefulness, and describes
      behavioral patterns of state in full-term as well as high-risk newborns. Specific
      intervention techniques are outlined for caregivers and parents, which address
      consolability, adjusting the environment, handling, and interactions. This
      information contributes to the nurse's ability to identify and assess
      neurobehavioral integrity and provides appropriate behavioral individualized
      developmental interventions during neonatal care.

PMID- 17505234
TI  - Sleep in the neonatal intensive care unit.
AB  - Recent experimental data suggest a strong role for sleep in brain development. As
      sleep is the predominant behavioral state in the term and especially the preterm
      newborn, these data underline the importance of respecting sleep duration and
      organization within the different sleep states. Polysomnography is the preferred
      technique used for identification of sleep state; however, behavioral
      observations-under the condition that the observer is well trained-may prove as
      efficient. Newborns hospitalized in the neonatal intensive care unit are exposed
      to many stimuli and care activities that disrupt their sleep organization and may
      have irreversible effects on their brain development. In order to improve the
      long-term neurobehavioral outcome of these high-risk subjects, a consistent care
      approach is proposed. Application of the Neonatal Individualized Developmental
      Care and Assessment Program decreases environmental stressful events and promotes
      harmonious well-being behaviors, based on an individual approach. This strategy
      has encouraging results, showing an increase in sleep duration under Neonatal
      Individualized Developmental Care and Assessment Program conditions, but further
      studies are needed to assess its long-term neurobehavioral impact.

PMID- 17505236
TI  - Sleep and kangaroo care: clinical practice in the newborn intensive care unit:
      where the baby sleeps...
AB  - This article provides a review of a change in practice within a Level III
      neonatal intensive care unit setting. The use of skin-to-skin holding as a means
      to secure parents' attachment to their infant, and support their child's rest and
      recovery in the neonatal intensive care unit, has been recognized historically
      and supported by research in this practice. The importance of sleep to the
      infant's developmental outcome was recognized and the use of skin-to-skin holding
      as a means of increasing stable infant sleep and rest was implemented. The
      implementation was based on published research, current practice within the
      nursery, and staff and family discussions. Implementation of skin-to-skin holding
      earlier in the newborn's neonatal intensive care unit course was accomplished by
      increasing interactive education, support, and ongoing review of unit practices
      and outcomes. Education regarding sleep states and cues was a focus of the
      project and understanding infant sleep assisted the staff in recognizing levels
      of restful sleep or restless sleep in infants. The implications of sleep and
      infant success in achieving discharge to home allowed the staff to see not only
      their role in infant sleep but also the parents' role in their newborn infant's
      sleep and growth in the nursery.

PMID- 17505237
TI  - Educating parents about the risk factors of sudden infant death syndrome: the
      role of neonatal intensive care unit and well baby nursery nurses.
AB  - Nurses in newborn nurseries and neonatal intensive care units are instrumental in
      educating parents about reducing the risk for SIDS. Nurse participation is
      acknowledged and encouraged in the current policy statement on SIDS Risk
      Reduction put forth by the American Academy of Pediatrics. Despite the decline in
      SIDS, it remains the leading cause of postneonatal infant mortality, and despite
      greater public compliance with the risk reduction guidelines there is room for
      improvement in how effectively and consistently they are disseminated. To
      facilitate nursing participation as educators, role models, and collaborators in
      the development of relevant hospital policies and procedures, we review the
      current recommendations, addressing issues that may serve as barriers to
      participation, describing the biological plausibility underlying risk-reducing
      practices, and presenting resources from which nurses may obtain teaching
      materials and model policies.

PMID- 17505238
TI  - Opposing effects of maternal and paternal socioeconomic status on neonatal
      feeding method, place of sleep, and maternal sleep time.
AB  - OBJECTIVE: This study was conducted to compare the relative influence of the
      socioeconomic status of both mothers and fathers on feeding method and
      cosleeping. METHODS: The time and method of feeding and sleeping were recorded in
      a log during the 4th-week postpartum and analyzed according to the parental
      Hollingshead Index of Social Position in 33 families with their first newborn.
      RESULTS: The effect of socioeconomic status on feeding and sleep was parent
      specific. Low socioeconomic status of the mother, but not the father, was
      associated with cosleeping (t = 2.39, P < .01); whereas, a low socioeconomic
      status of the father, but not the mother, was associated with bottle-feeding
      rather than breast-feeding (t = 1.94, P < .05). CONCLUSIONS: Socioeconomic status
      of the parents differentially affects neonatal care. Programs to increase breast
      feeding rates would be most effective if designed for and aimed at the fathers.

PMID- 17505239
TI  - Johari window: a model for communicating to each other.

PMID- 17505241
TI  - Qualitative research proposals--part III: sampling and data collection.

PMID- 17505244
TI  - Preventing and managing skin tears: a review.
AB  - Skin tears are an increasingly common problem in frail elders, and the wound,
      ostomy, and continence (WOC) nurse must be knowledgeable regarding both
      prevention and management of these lesions. A literature review was conducted to
      identify current concepts regarding management of skin tears. Articles reviewed
      provided numerous suggested interventions and protocols. Recurring themes were
      prevention of skin tears whenever possible and management of existing lesions
      with products that manage the exudate, maintain a moist surface, and prevent
      additional trauma.

PMID- 17505242
TI  - Discharge knowledge and concerns of patients going home with a wound.
AB  - PURPOSE: To examine patients' wound care knowledge and concerns prior to
      discharge from an acute care hospital. DESIGN: Comparative descriptive study of
      patients with wounds. SETTING AND SUBJECTS: Participants (N = 76) included 17 men
      and 59 women who were African American (n = 33, 43.4%) or Caucasian (n = 43,
      56.6%) and ranged in age from 20 to 83 years (M = 48, SD = 13). There were 67
      persons with acute wounds and 9 with chronic wounds. All were scheduled to be
      discharged home from a large urban acute care hospital. INSTRUMENTS: The
      questionnaire for this study included the following sections: Demographic,
      Admission and Discharge, Health, Wound Care, Beliefs about Wounds and their Care,
      Pain and Wounds, Literacy and Learning, and Discharge Concerns. RESULTS:
      Participants' greatest concerns about going home were: (1) how active to be at
      home, (2) wound pain, (3) looking for wound complications, and (4) watching for
      wound infection. Many participants did not know the dressing (38.2%) or solution
      to cleanse the wound (58.7%) at home. Most had taken care of a wound before
      (67.1%), could see (68.4%) and reach (69.7%) the wound, and had looked at it
      (64.5%) during the hospitalization. Patients with acute and chronic wounds did
      not differ significantly in their concerns about their wound or their fear of
      taking care of their wound. Participants generally had appropriate knowledge
      about wounds and hand washing, nutrition, going out of the home, and cigarette
      smoking. They had incorrect information about drying out wounds and leaving them
      open to breathe the air. The majority of patients with chronic wounds preferred
      getting answers to questions about their wound and its care from their physician
      followed by their clinic and family/friends. Patients with acute wounds
      overwhelmingly chose their physician as a source of information about their wound
      and its care, followed by calling a nurse at the hospital and using the Internet.
      CONCLUSIONS: Patients were able to verbalize their concerns about going home with
      a wound. Concerns about discharge may help to direct patient teaching in
      preparation for discharge. Teaching literature could include the most common
      concerns, as well as ways to avoid misinformation about wound care. Discharge
      teaching needs to begin early so that patients feel they have adequate time to
      learn and ask questions. Further research is needed about patients' wound care
      knowledge and discharge concerns.

PMID- 17505245
TI  - Prevalence of incontinence and associated skin injury in the acute care
      inpatient.
AB  - PURPOSE: We examined the prevalence of incontinence and skin injury in areas
      exposed to incontinence among inpatients at 2 hospitals. SUBJECTS AND SETTING:
      Acute care patients in medical, surgical, and intensive care units at a community
      and teaching hospital were surveyed to determine the rates of urinary and fecal
      incontinence and the prevalence of incontinence-associated dermatitis or skin
      ulceration. INSTRUMENT: A data collection form that queried patient
      characteristics was completed. The presence of hypoalbuminemia (< or = 3.4 g/dL)
      and nutrition, friction and shear, and mobility status (using Braden scale
      scores) were also recorded. This instrument was designed by this research team
      and tested in a pilot study. RESULTS: A total of 608 patients age 4 years and
      older were surveyed. The overall prevalence of incontinence in the survey was
      19.7% (120 of 608). One hundred seven patients (17.6%) were incontinent of stool.
      Fecal incontinence was more frequent than urinary incontinence overall, by gender
      and across the different age groups. However, 201 (33%) of the inpatients had
      indwelling urinary catheters and were counted as continent of urine. The highest
      prevalence of incontinence was found in the oldest age group (80+ years). Some
      type of injury to the skin was observed in 42.5% of the 120 patients who were
      incontinent. Hypoalbuminemia and poor nutritional status were more commonly noted
      in patients with skin injury associated with fecal incontinence. CONCLUSION:
      Fecal and urinary incontinence are common among patients in the acute care
      setting. Fecal incontinence is associated with hypoalbuminemia and poor
      nutritional status and is associated with a higher rate of skin injury.

PMID- 17505246
TI  - Urinary incontinence after radical prostatectomy: can men at risk be identified
      preoperatively?
AB  - BACKGROUND: Incontinence after radical prostatectomy for early stage prostate
      cancer can significantly affect quality of life. Identification of risk factors
      preoperatively would enable clinicians to counsel men and their partners about
      the risk of incontinence following surgery. We conducted a population-based study
      to identify subjective and objective preoperative factors, other than PSA and
      Gleason score, that may predict urinary incontinence following radical
      prostatectomy. METHODS: Men booked for radical prostatectomy at 2 sites in
      Alberta were enrolled prospectively. Assessment was completed 2 weeks prior to
      surgery and included the International Prostate Symptom Score (IPSS) with a
      single quality-of-life (QOL) question, 24-hour pad test, and bladder diary. These
      parameters were repeated at 3 and 12 months postoperatively. A model predicting
      incontinence was developed using stepwise multivariable logistic regression
      analysis. Incontinence was defined as more than 8 g of urine loss on 24-hour pad
      test. RESULTS: A total of 245 patients from 2 centers were enrolled; 228 (93%)
      completed data collection up to 12 months postsurgery. At the baseline
      preoperative assessment, 4% (10/228) of subjects had > or = 8 g of urine loss on
      24-hour pad test, although these and all other subjects described complete
      continence. At 3 months postop, 43% had > or = 8 g on 24-hour pad testing (our
      definition of incontinence) (median 31 g, range 8.3-1654 g, SD 219.12); at 12
      months, 15% had more than 8 g of urine loss on pad test (median 21.0 g, range 8.1
      3380 g, SD 578.0). For all subjects, mean IPSS and the single QOL scores at
      baseline (7.4 and 1.5) did not change significantly at 3 months (7.2 and 2.5),
      but both were lower than or equal to baseline at 12 months (5.4 and 1.5). The
      IPSS was predictive of incontinence at 3 months, but not at 12 months. Bladder
      diary did not correlate with IPSS. Risk factors affecting continence at 12 months
      were preoperative urine loss > or = 8 g, previous transurethral resection of
      prostate (TURP), and age greater than 65 years. CONCLUSION: Our results support
      previous research on risk factors for incontinence after radical prostatectomy
      and add to the current data by having presurgery (baseline) measures.
      Interestingly, a small percentage of men (4%) who reported complete continence
      were incontinent preoperatively, based on our definition of > or = 8 g weight
      gain on 24-hour pad test. Identified preoperative risk factors affecting
      continence were increasing age, baseline incontinence, and previous TURP. Mean
      IPSS was lower at 12 months than at baseline, suggesting that even mildly
      symptomatic men will improve after surgery. Men reported that regular contact
      with the continence research nurse provided a much-appreciated source of informed
      support as they recovered.

PMID- 17505248
TI  - Care of the indwelling urinary catheter: is it evidence based?
AB  - This article reviews evidence-based practice guidelines for the care of
      indwelling urinary catheters in acute, long-term, and home care settings. Upon
      completion of this reading, the clinician will have a better understanding of
      urinary catheter management of short-term and long-term placement, possible
      complications from catheter use, the importance of alternative options for
      catheter placement, and recommendations for patient education. Basic infection
      prevention, existing catheter types, and the differences between men and women
      with the use of these catheters will also be addressed. Practices that are no
      longer recommended, as well as present research on the use of silver alloy
      catheters and their role in preventing infection, are summarized.

PMID- 17505249
TI  - Current evidence on intermittent catheterization: sterile single-use catheters or
      clean reused catheters and the incidence of UTI.
AB  - PURPOSE: Intermittent catheterization is a commonly prescribed procedure for
      people with incomplete bladder emptying not managed by other methods. The most
      frequent complication of intermittent catheterization is urinary tract infection
      (UTI). It is unclear what strategies, including sterile vs clean catheters or
      coated vs uncoated PVC catheters, affect the incidence of UTIs. This systematic
      review summarizes current evidence on the relationship between sterile single-use
      catheters or clean reused catheters and the incidence of UTIs. SEARCH STRATEGY:
      The Cochrane Incontinence Group trials register, Medline, EMBASE, CINAHL, and
      ERIC were searched, plus the reference lists of relevant articles and conference
      proceedings. Randomized controlled trials comparing at least two different
      products or methods for intermittent catheterization were included. DATA
      COLLECTION AND ANALYSIS: Three reviewers assessed the methodological quality of
      trials and abstracted data. MAIN RESULTS: Of the 13 trials that met the inclusion
      criteria on intermittent catheterization protocols, there was considerable
      variation in length of follow-up, definitions of UTI, and numbers of subjects.
      Attrition was a problem for several studies, and all were underpowered. Several
      studies were more than 10 years old, and outcome measures were imprecise, making
      it difficult to draw conclusions on the benefit of one catheterization method
      over another. CONCLUSIONS: There are no definitive studies illustrating that
      incidence of UTIs is affected by sterile single-use or coated catheters compared
      to clean reused catheters. However the current research base is weak and design
      issues are significant. Based on the current data, it is not possible to state
      that one catheter method is better than another and further research on the topic
      is strongly recommended.

PMID- 17505250
TI  - Extravasation injury as a result of VAD chemotherapy.

PMID- 17505251
TI  - Extravasation injuries: implications for WOC nursing.

PMID- 17505252
TI  - Chikungunya infection: an emerging rheumatism among travelers returned from
      Indian Ocean islands. Report of 47 cases.
AB  - A large chikungunya virus (CHIKV) outbreak emerged in 2005-2006 in the Indian
      Ocean islands, including Comoros, Mayotte, Mauritius, the Seychelles, and
      particularly in Reunion Island where 35% of 770,000 inhabitants were infected in
      6 months. More recently, circulation of the virus has been documented in
      Madagascar and in India where CHIKV is spreading rapidly. CHIKV-infected visitors
      have returned home to nonendemic regions from these islands. We conducted a 14
      month prospective observational study on the clinical aspects of CHIKV infection
      imported to Marseilles, France, in travelers returning from the Indian Ocean
      islands. A total of 47 patients have been diagnosed with imported CHIKV infection
      confirmed by serology, reverse transcription-polymerase chain reaction, and/or
      viral culture. At the early stage of the disease (within 10 days of the disease
      onset), fever was present in 45 of 47 patients. A rash was present in the first
      week in 25 cases. All patients suffered with arthritis. The most frequently
      affected joints were fingers, wrists, toes, and ankles. Eight patients were
      hospitalized during the acute stage, including 2 severe life-threatening cases. A
      total of 38 patients remained symptomatic after the tenth day with chronic
      peripheral rheumatism, characterized by severe joint pain and multiple
      tenosynovitis, with a dramatically limited ability to ambulate and carry out
      activities in daily life. Three patients were hospitalized at this stage for
      severe persistent handicap. Follow-up demonstrated slow improvement in joint pain
      and stiffness despite symptomatic treatment, mainly antiinflammatory and
      analgesic drugs. In the current series we describe 2 stages of the disease, an
      initial severe febrile and eruptive polyarthritis, followed by disabling
      peripheral rheumatism that can persist for months. We point out the possibility
      of transitory peripheral vascular disorders during the second stage and the
      occasional benefit of short-term corticosteroids. As CHIKV could spread
      throughout the world, all physicians should be prepared to encounter this
      arboviral infection.

PMID- 17505253
TI  - Comparison of clinical manifestations and outcome of community-acquired
      bloodstream infections among the oldest old, elderly, and adult patients.
AB  - Valid studies comparing the clinical characteristics among adult, elderly, and
      the oldest old bacteremic patients are lacking. We conducted a prospective,
      observational study in the emergency department (ED) of a university medical
      center between June 2001 and June 2002. All patients >18 years of age who
      registered in the ED with a clinically significant, culture-positive, bloodstream
      infection (BSI) were enrolled. Patients were divided into 3 groups based on age:
      1) oldest old (> or =85 yr), 2) elderly (65-84 yr), and 3) adult (18-64 yr). The
      clinical and laboratory manifestations and 30-day mortality were recorded. Group
      comparisons were performed using the chi-square test or analysis of variance
      (ANOVA) test, as indicated. Survival was analyzed using the Kaplan-Meier method
      and the Cox-regression model, adjusted for potential confounders.A total of 890
      cases of community-acquired BSI were eligible for analysis. Compared to the adult
      group, both the elderly and the oldest old patients had more atypical clinical
      manifestations, a higher propensity to develop organ failure, and a worse
      prognosis. Elderly patients had significantly less tachycardia (p = 0.001), but
      more acute respiratory (p = 0.007) and renal failure (p = 0.037); the oldest old
      patients had more afebrile episodes (p = 0.006), leukocytosis (p = 0.012), and
      more patients developed respiratory failure (p = 0.009), acute renal failure (p =
      0.011), septic shock (p = 0.022), and altered mental status (p = 0.013). Urinary
      tract infections were the main source of BSI for both the elderly and oldest old,
      while the oldest old patients had significantly more pneumonia than the elderly
      or adults. As a group, older patients had fewer signs and symptoms of BSI, but a
      higher risk of organ failure and a worse prognosis than younger patients.

PMID- 17505254
TI  - Aseptic abscesses: a study of 30 patients with or without inflammatory bowel
      disease and review of the literature.
AB  - Aseptic abscesses (AA) are characterized by deep, sterile, round lesions
      consisting of neutrophil that do not respond to antibiotics but improve
      dramatically with corticosteroids. We report the clinical, laboratory, and
      radiologic characteristics and the associated conditions of 29 patients from the
      French Register on AA plus 1 patient from the Netherlands.The mean age of
      patients at AA diagnosis was 29 years (SD = 14). The main clinical manifestations
      of AA were fever (90%), abdominal pain (67%), and weight loss (50%). Duration of
      symptoms was 4.7 months on average until abscesses were discovered. The abscesses
      involved the spleen in 27/29 patients (93%; the thirtieth patient had a personal
      history of splenectomy after a trauma). In 7 they were unifocal and in the others
      they were multifocal, involving in addition the abdominal lymph nodes in 14
      (48%), liver in 12 (40%), lung in 5 (17%), pancreas in 2 (7%), and brain in 2
      (7%). They were not splenic in 3, including 2 with abdominal lymph nodes and 1
      with superficial lymph nodes and testicle and lung involvement. Twenty-two
      patients (70%) had elevated white blood cell and neutrophil count; antineutrophil
      cytoplasmic autoantibodies with a perinuclear, cytoplasmic or atypical pattern
      (negative for antiproteinase 3 and negative for antimyeloperoxidase except for 1)
      were positive in 21% of the 24 patients tested. Twenty-one patients had
      inflammatory bowel disease (IBD), which preceded the occurrence of abscesses in
      7, was concomitant in 7, and appeared secondarily in 7. Six patients had
      neutrophilic dermatosis (20%), 3 had relapsing polychondritis as an associated
      condition, and 3 others had monoclonal gammopathy of undetermined significance.
      Three patients had no associated condition. Splenectomy was performed in 15 (52%)
      patients. All patients received steroid therapy. Thirteen (43%) were given
      additional immunosuppressive therapy, 1 immediately and the others after a
      relapse, of whom 3 were also treated by anti-tumor necrosis factor-alpha agents.
      Mean follow-up was 7 years. Eighteen (60%) patients experienced 1 or several
      relapses, but there was no death related to AA. Relapses occurred on
      immunosuppressive therapy in 2 patients and off immunosuppressive therapy in the
      others while corticosteroids were being tapered. We surveyed the literature and
      analyzed 19 additional cases. AA is an emergent and probably underrecognized
      entity. It represents an apparently noninfectious inflammatory disorder involving
      neutrophils that responds to corticosteroid therapy. AA mainly affects patients
      with IBD but also affects those with other conditions, or with no other apparent
      disease.

PMID- 17505255
TI  - Systemic histoplasmosis: a 15-year retrospective institutional review of 111
      patients.
AB  - To our knowledge, an institutional review of systemic histoplasmosis has not been
      conducted in the United States since the major outbreaks in Indianapolis in 1978
      4982. We conducted a retrospective review of all patients with systemic
      histoplasmosis diagnosed at Mayo Clinic over a 15-year period. The case
      definitions employed were based on an international consensus statement by the
      European Organization for Research and Treatment of Cancer/Invasive Fungal
      Infections Cooperative Group (EORTC/IFICG) and the National Institute of Allergy
      and Infectious Diseases Mycoses Study Group (MSG). One hundred eleven patients
      with systemic histoplasmosis were identified between January 1, 1991, and
      December 31, 2005. Of these, 78 patients had disseminated histoplasmosis and 55
      patients had Histoplasma capsulatum fungemia. The mean age of patients was 55
      years, 66% were male, and 98% were white. Fifty-nine percent of patients were
      immunocompromised. Fever was the most frequently reported symptom (63%), followed
      by respiratory complaints (43%) and weight loss (37%). The peripheral white blood
      cell count was <3000 cells/mm in 28%, hemoglobin was <10 g/dL in 29%, and
      platelet count was <150,000 cells/mm in 41% of patients. Liver enzymes were
      elevated (alanine aminotransferase >60 U/L in 39%, aspartate aminotransferase >60
      U/L in 27%), alkaline phosphatase was >200 U/L in 55%, and albumin was <3.5 g/dL
      in 70%. Serologic and histopathologic examinations were each positive in 75% of
      cases, Histoplasma urine antigen screening was positive in 80%, and H. capsulatum
      was culture positive in 84%. Forty-seven percent of patients were sequentially
      treated with an amphotericin B-containing product followed by itraconazole, 31%
      received itraconazole alone, and 7% received an amphotericin B-containing product
      only. Another 13% of patients did not receive antifungal treatment, and the
      remaining 2% did not have treatment data available. Sixty percent of patients
      required hospitalization, and in hospital mortality was 6% with a median survival
      time of 61 days. The relapse rate was 9%, with a median relapse-free survival of
      857 days. Systemic histoplasmosis should be suspected in patients who have lived
      in endemic areas with fever, bone marrow suppression, and elevated hepatic
      enzymes, particularly if they are immunocompromised. Evaluation including a
      combination of Histoplasma serologic screening, urine antigen assay, and fungal
      culture will secure the diagnosis in most cases.

PMID- 17505256
TI  - Renal granulomatoses: a retrospective study of 40 cases and review of the
      literature.
AB  - Renal granulomatoses represent 0.5%-0.9% of nephropathies examined by renal
      biopsies. Granulomas can be isolated to the kidney or associated with other
      tissue involvement. We describe 40 consecutive patients with renal
      granulomatoses, associated with pauci-immune crescentic glomerulonephritis in 2
      patients and with vasculitis in another, seen in northeastern Paris hospitals
      between January 1991 and February 2004. The criterion for inclusion was the
      presence of 1 or more epithelioid granulomas in the renal interstitium. Our
      population of 25 men and 15 women had a median age of 53 years. All patients
      suffered from renal insufficiency with median creatininemia of 236.8 micromol/L
      (range, 124-805 micromol/L), associated with hypertension (25%), median
      proteinuria of 0.6 g/24 h (range, 0.08-3.00 g/24 h), microscopic hematuria (15%)
      and leukocyturia (22.5%). Histologic examination of extrarenal specimens detected
      granulomas in 82.4% of the bronchial biopsies taken, and in 100% of the 2 skin
      biopsies, the 2 lymph-node biopsies, and the liver and colon biopsies. The
      following etiologies were retained: sarcoidosis for 20 (50%) patients, drug
      induced for 7 (17.5%), tuberculosis for 3 (7.5%), Wegener granulomatosis for 2
      (5%), and leprosy, Mycobacterium avium infection, and Crohn disease for 1 (2.5%)
      patient each. No etiology could be identified for 5 (12.5%) patients. Treatment
      must be adapted to the etiology of each case. The renal outcome after treatment
      was generally favorable, with the estimated median creatinine clearance
      increasing from 26 mL/min (range, 5.4-80.0 mL/min) to 46.5 mL/min (range, 0-118
      mL/min) after a median follow-up of 35.5 months (range, 3-158 mo). Nonetheless,
      32 patients had persistent renal insufficiency; 1 required hemodialysis and
      another underwent renal transplantation. Sarcoidosis and medications are the most
      common causes of renal granulomatosis. Idiopathic and drug-induced forms do not
      relapse after treatment discontinuation, and remission persists at long-term
      follow-up.

PMID- 17505257
TI  - Alveolar hemorrhage in anti-basement membrane antibody disease: a series of 28
      cases.
AB  - Anti-basement membrane antibody disease is a rare disorder characterized by the
      presence of autoantibodies binding to the alveolar and glomerular basement
      membranes, and mediating both alveolar hemorrhage and acute glomerulonephritis.
      We retrospectively analyzed 28 cases of anti-basement membrane antibody disease
      with alveolar hemorrhage proven by bronchoalveolar lavage. The median age of
      patients at diagnosis was 23 years; 68% were male, 89% were active smokers, and
      36% were exposed to some other inhaled agent. At diagnosis, 46% had predominant
      pulmonary involvement with normal initial serum creatinine. Lung function tests
      disclosed a restrictive ventilatory defect in 28% (n = 11) and hypoxemia
      (moderate in 29% and severe in 29%, n = 21). Carbon monoxide transfer factor was
      elevated in only 25% (n = 12). Bronchoalveolar lavage was more sensitive than any
      other criterion for detecting alveolar hemorrhage. After onset of treatment, new
      hemoptysis or transient worsening of hypoxemia occurred in 29% but did not affect
      pulmonary outcome. In contrast, worsening of renal function occurred in 33% and
      adversely affected renal outcome. At last follow-up (median, 2.6 yr; n = 24), all
      patients were alive and a complete cure was achieved in 50%. Long-term dialysis
      or renal transplantation was required in 42%, and 8% had mild chronic renal
      insufficiency. Last chest X-ray was normal in all cases, and no patient had
      respiratory insufficiency. All patients with predominant pulmonary involvement at
      presentation maintained independent renal function. In summary, this cohort was
      characterized by frequent exposure to tobacco smoking and other inhaled agents,
      and a constantly favorable pulmonary outcome contrasting with frequent chronic
      renal failure. Renal outcome was excellent in the subgroup of patients with
      predominant pulmonary involvement.

PMID- 17505258
TI  - Melanoma vaccines: in search of a clinical paradigm.

PMID- 17505259
TI  - Cyclooxygenase-2 (COX-2): first immunohistochemical marker distinguishing early
      cutaneous melanomas from benign melanocytic skin tumours.
AB  - We have reported recently that changes in expression level of COX-2 are
      correlated with development and progression of human melanoma. In this study, we
      investigated whether the COX-2 expression level might be a useful
      immunohistochemical marker for distinguishing cutaneous melanomas from benign
      melanocytic lesions. Up to now, immunohistochemical markers have not ensured
      satisfactory sensitivity and specificity of differential pathologic diagnosis of
      melanoma. The expression of COX-2 was determined immunohistochemically in
      formalin-fixed, paraffin-embedded specimens of 33 early Clark I/II melanomas and
      58 naevi. Mean COX-2 expression in melanomas was significantly stronger than in
      naevi (P approximately 10(-13)). A simple diagnostic algorithm using threshold
      values of the COX-2 expression level allows for differentiation between early
      melanomas and naevi with high sensitivity (Se) and specificity (Sp) (for Se
      between 91 and 100%, Sp values change between 96.5 and 51.7%). Areas under the
      receiver operating characteristic curves were, respectively, 0.97+/-0.02 and
      0.86+/-0.04 for the COX-2 expression in central and border regions of the
      lesions. For all the melanomas (not only the early ones),the respective areas
      under the ROC curve values were 0.98+/-0.01 and 0.97+/-0.02. In conclusion, COX-2
      is the first immunohistochemical marker that allows the distinguishing of early
      melanomas from benign melanocytic lesions with both high sensitivity and
      specificity.

PMID- 17505260
TI  - F-18 fluorodeoxy-D-glucose positron emission tomography scan in the initial
      evaluation of patients with a primary melanoma thicker than 4 mm.
AB  - Metabolic imaging with F-18 fluorodeoxy-D-glucose positron emission tomography is
      one of the most sensitive and non-invasive techniques, and has proved useful in
      melanoma. We designed, in 2004, at the Institute Gustave Roussy, a prospective
      study to determine the value of F-18 fluorodeoxy-D-glucose positron emission
      tomography scanning in the detection of regional and/or distant metastasis in 25
      new patients referred for the treatment of a primary melanoma thicker than 4 mm
      (tumor node metastases stage T4). The sentinel lymph node biopsy was proposed for
      all the patients without a palpable regional lymph node. Abnormal positron
      emission tomography scan findings were correlated to available histological data
      and to the course of the disease. The F-18 fluorodeoxy-D-glucose positron
      emission tomography scan identified 0/2 intact primary melanomas, 1/4 residual
      primary melanomas after limited excision, 0/6 lymph node basins with
      micrometastasis, 4/4 lymph node basins with enlarged palpable lymph nodes and 0
      distant metastasis. The sensitivity and specificity of positron emission
      tomography scans for microscopic lymph node disease in basins were, respectively,
      0 and 92%. A false-positive F-18 fluorodeoxy-D-glucose positron emission
      tomography result in a cervical basin led to a useless cervical lymph node
      dissection. In three patients, the positron emission tomography scan was positive
      in distant sites but none of these foci represented a true metastasis. In
      conclusion, it is not useful to include a positron emission tomography scan in
      the initial work-up of patients with primary melanoma, even in patients with
      thick primary melanomas (>4 mm). Sentinel lymph node biopsy remains the technique
      of choice for the most accurate initial staging.

PMID- 17505261
TI  - The 18 kDa isoform of basic fibroblast growth factor is sufficient to stimulate
      human melanoma growth and angiogenesis.
AB  - Basic fibroblast growth factor is the best-characterized autocrine growth factor
      in melanoma development and progression. We hypothesized that basic fibroblast
      growth factor might induce a more aggressive phenotype dependent on the amount of
      protein expressed in melanoma. Two human melanoma cell lines, M14 and 1F6, known
      to have low endogenous basic fibroblast growth factor expression and slow growth
      as subcutaneous xenografts, were stably transfected with vectors encoding either
      the 18 kDa or all (ALL) isoform proteins of human basic fibroblast growth factor.
      Different clones overexpressing the 18 kDa or ALL basic fibroblast growth factor
      proteins were easily obtained. Increased levels of basic fibroblast growth factor
      were secreted in conditioned medium and stored on the extracellular membrane.
      Biological activity of the overexpressed basic fibroblast growth factor was
      confirmed in a human umbilical vein endothelial cell proliferation assay. In 1F6
      cells, overexpression of either 18 kDa or ALL basic fibroblast growth factor
      proteins resulted in up to two-fold shorter in-vitro doubling times (P<0.05). In
      addition, in vivo, both 18 kDa and ALL basic fibroblast growth factor
      overexpressing 1F6 subcutaneous xenografts displayed significantly higher growth
      rates (P<0.05). In contrast, no major differences in in-vitro and in-vivo
      doubling times were observed when 18 kDa or ALL isoforms of basic fibroblast
      growth factor were overexpressed in M14 cells. Interestingly, basic fibroblast
      growth factor overexpression only affected the microvasculature in 1F6
      xenografts. Although blood vessels in 1F6 parent tumors were large, 1F6 tumors
      overexpressing basic fibroblast growth factor contained numerous small,
      compressed vessels. Taken together, overexpression of the 18 kDa basic fibroblast
      growth factor protein only can promote autocrine melanoma cell growth and
      paracrine-driven angiogenesis.

PMID- 17505262
TI  - Melanoma-infiltrating dendritic cells induce protective antitumor responses
      mediated by T cells.
AB  - Dendritic cells are the most potent antigen-presenting cells inducing innate and
      adaptive immune response. Dendritic cells infiltrate melanomas, but their ability
      to induce host antitumor immunity remains obscure. In a previous study, we have
      observed that melanoma-infiltrating dendritic cells have the capacity to process
      antigens and migrate to lymph nodes to prime T lymphocytes. Here, we observed
      that melanoma-infiltrating dendritic cells extracted from melanoma without any
      additional manipulations were able to protect naive mice against a lethal
      challenge with the tumor. Remarkably, this was achieved with reinjection of 10(5)
      melanoma-infiltrating dendritic cells, a number that did not exceed the total
      number of melanoma-infiltrating dendritic cells recovered from one single tumor.
      Three observations indicate that protection was due to the natural loading of
      melanoma-infiltrating dendritic cells with tumor antigens. First, the protective
      effect was not observed with equivalent numbers of bone marrow-derived dendritic
      cells. Second, the protection induced was specific for the tumor from which the
      tumor-infiltrating dendritic cells were isolated. Third, depletion experiments
      indicate that both CD4+ and CD8+ T lymphocytes were required during the effector
      phase of the antitumor response. Hence, designing strategies aimed at rendering
      melanoma-infiltrating dendritic cells visible to host T cells may boost
      spontaneous antitumor immunity.

PMID- 17505263
TI  - Recombinant interferon alpha-2b and coenzyme Q10 as a postsurgical adjuvant
      therapy for melanoma: a 3-year trial with recombinant interferon-alpha and 5-year
      follow-up.
AB  - Early surgical intervention remains the most successful therapy for melanoma.
      Despite better outcomes observed in soft tissue and lymph node metastases, the
      results of pharmacological therapies are still disappointing. Currently, there is
      no standard adjuvant therapy for melanoma. Low concentrations of coenzyme Q10
      have been demonstrated in melanoma cell lines and in sera of melanoma patients.
      These data and the results of clinical trials of patients with other advanced
      cancers prompted this study of the long-term administration of an optimized dose
      of recombinant interferon alpha-2b and coenzyme Q10 to patients with stage I and
      II melanoma. A 3-year trial envisaging uninterrupted treatment with low-dose
      recombinant interferon alpha-2b (9 000 000 000 IU weekly) administered twice
      daily and coenzyme Q10 (400 mg/day) was conducted in patients with stage I and II
      melanoma (American Joint Committee on Cancer criteria 2002) and surgically
      removed lesions. Treatment efficacy was evaluated as incidence of recurrences at
      5 years. All patients completed the treatment and the follow-up. Significantly
      different rates of disease progression were observed in the interferon+coenzyme
      Q10 and the interferon group for both stages. No patient withdrew from the study
      owing to side effects. Long-term administration of an optimized dose of
      recombinant interferon alpha-2b in combination with coenzyme Q10 seemed to induce
      significantly decreased rates of recurrence and had negligible adverse effects. A
      survival study could not be undertaken owing to the small patient sample and the
      short duration of follow-up.

PMID- 17505264
TI  - CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based
      population.
AB  - Germline mutations of the CDKN2A and CDK4 genes explain a significant proportion
      of familial melanoma. To date, there have been few published estimations of the
      prevalence of such mutations in sporadic melanoma patients. In this study, we
      investigated CDKN2A and CDK4 exon 2 for germline mutations in 125 consecutive
      cutaneous malignant melanoma patients recruited through the Latvian Oncological
      Center, using amplicon melting analysis and sequencing. No disease-related CDKN2A
      germline mutations were identified in any of the melanoma patients analysed but
      the previously described CDK4 mutation, Arg24His, was found in one patient with a
      family history of melanoma. CDKN2A polymorphisms were studied as putative low
      penetrance susceptibility genes. The proportion of cases with polymorphisms in
      this Latvian melanoma population was Ala148Thr (c.442G>A) (6%), 500 C/G
      (c.*29C>G) (18%), and 540 C/T (c.*69C>T) (20%); however, only the frequency of
      the Ala148Thr polymorphism was higher in melanoma patients than in 203 controls
      (6 versus 1%, P=0.03). Ala148Thr has also been reported in association with
      melanoma in a Polish series but not in an English series. We therefore examined
      the Ala148Thr carrier's haplotype in 10 Latvian and 39 Polish samples. No
      significant difference was seen between these populations and the predominant
      haplotype observed in English samples, giving no indication that the discrepancy
      could be explained by population differences in linkage disequilibrium. In
      summary, our results show that germline mutations at the CDKN2A locus are rare in
      sporadic melanoma in Latvia. The study does, however, provide some additional
      evidence for a role for the CDKN2A polymorphism Ala148Thr as a low penetrance
      susceptibility gene. The detected CDK4 exon 2 mutation was found in only the
      seventh family identified worldwide with a germline CDK4 mutation.

PMID- 17505265
TI  - Endostatin plus interferon-alpha2b therapy for metastatic melanoma: a novel
      combination of antiangiogenic and immunomodulatory agents.
AB  - In patients with stage IIB-III disease, adjuvant high-dose interferon-alpha2b has
      shown clinical benefit, although metastatic melanoma is currently without any
      known survival-prolonging therapy. Angiogenesis has been considered important in
      melanoma progression, and endostatin is an angiogenesis inhibitor with antitumor
      activity that has shown promising results in murine model systems, prompting
      investigation of a formulation of rh-Endostatin (EntreMed, Rockville, Maryland,
      USA) alone and with interferon in metastatic melanoma. Patients were randomly
      assigned to receive interferon alpha2b (Schering-Plough) 10 million units/m(2)
      subcutaneously three times a week plus rh-Endostatin 45 mg/m(2) subcutaneously
      every 12 h (arm A) vs. rh-Endostatin alone (arm B). Twenty-one patients (age
      range 31-77 years, median age 54, 12 men and nine women, 17 cutaneous, and four
      ocular melanomas) were enrolled. No antitumor responses were observed, and no
      significant differences were noted in time to progression or overall survival.
      Two patients had stable disease enduring more than 30 weeks on treatment. Serum
      endostatin levels increased significantly 4 weeks after treatment in both groups.
      Basic fibroblast growth factor levels in urine were significantly lower following
      treatment in patients on arm B (P=0.043). The percentage of circulating
      endothelial cells was increased in five evaluable patients 4 weeks after
      treatment. Low titer (<or=1:25) IgG antibodies against the rh-Endo formulation
      were detected in two patients (one per arm) in cycle 4. In conclusion, interferon
      did not improve response rate of rh-Endo although prolonged disease stability was
      observed in two patients. Better laboratory correlates of antiangiogenic response
      are needed, and the predictive value of circulating endothelial cells warrants
      further evaluation.

PMID- 17505266
TI  - Association of hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber
      syndrome) and malignant melanoma in two patients.
AB  - Hereditary haemorrhagic telangiectasia is a rare autosomal-dominant vascular
      dysplasia characterized by telangiectasia, recurrent epistaxis, visceral
      arteriovenous manifestations and inheritance. Several reports have pointed out
      that hereditary haemorrhagic telangiectasia could be associated with various
      neoplasm development. Malignant melanoma has occasionally been reported. We
      herein describe two cases of fatal malignant melanoma that developed in patients
      with hereditary haemorrhagic telangiectasia. The potential pathogenetic
      relationship between those two diseases is discussed.

PMID- 17505267
TI  - Screening for iron deficiency anemia in at risk children in the pediatric
      emergency department: a survey of Canadian pediatric emergency department
      physicians.
AB  - OBJECTIVE: To determine the attitudes and reported practices of physicians
      regarding screening for iron deficiency anemia in at-risk children in pediatric
      emergency departments (PEDs) across Canada. METHODS: A standardized survey was
      mailed to 183 PED physicians at 10 tertiary care PED across Canada. The practices
      and attitudes regarding screening for iron deficiency anemia were collected via a
      questionnaire consisting of single select closed-ended items and items which
      required ranking in order of importance. RESULTS: Sixty-one percent (111/183) of
      physicians responded to the survey. Ninety-six percent of respondents do not
      routinely screen for iron deficiency anemia. One third of respondents believed
      that screening for iron deficiency anemia in the PED is possible. The remaining
      stated lack of time, difficulty with follow-up, it not being an emergent issue
      and cost as prohibitive factors. One third of participants stated that 21% to 40%
      of the pediatric patients seen in their PED did not have a primary care
      physician. The main considerations in deciding on whom to perform venipuncture
      were based on dietary history and physical examination with a history of
      consumption of milk greater than 24 ounces per day (94%) and conjunctival or skin
      pallor (97%, 94%, respectively) selected as the most important items. CONCLUSION:
      The results of this study indicate that Canadian PED physicians are not routinely
      screening for iron deficiency anemia, although they demonstrate knowledge of the
      risk factors for iron deficiency anemia and recognize the importance of diagnosis
      and treatment to prevent long-term morbidity.

PMID- 17505268
TI  - Immunization histories given by adult caregivers accompanying children 3-36
      months to the emergency department: are their histories valid for the Haemophilus
      influenzae B and pneumococcal vaccines?
AB  - OBJECTIVE: To obtain immunization histories from adult caregivers accompanying
      children to the emergency department (ED), to determine the accuracy of the
      caregiver's report for the Haemophilus influenzae B (Hib)and 7-valent
      pneumococcal vaccine (PCV7). METHODS: This was a prospective, observational study
      of children age 3 to 36 months presenting to the Albert Einstein Medical Center
      ED during the period of November 1, 2004, through January 31, 2005. Caregivers
      were asked to complete a questionnaire about their child's immunization status
      and if the child's vaccinations were up-to-date. Immunization records were
      obtained from the child's most recent primary care physician (PCP) to determine
      whether the caregiver's report was correct for PCV7 and Hib. Children were
      considered delayed if they were more than 30 days past due date for one or both
      vaccines according to the PCP records. RESULTS: Of 205 PCP offices contacted, we
      were able to obtain 173 immunization records for our analysis. Examination of
      vaccine records showed that 109 (63.0%) of the 173 children were up-to-date on
      both immunizations. When the child's caregiver was asked if shots were up-to
      date, 159 (91.9%) of 173 said that all shots were given, and only 14 (8.1%) of
      173 reported being behind schedule. Of the adults reporting the child up to date,
      105 (66.0%) of the 159 children were confirmed to be up-to-date. Thus, 34.0% of
      caregivers were incorrect in stating that their child's immunization status was
      up-to-date for both these vaccines. CONCLUSIONS: Caregiver report was determined
      to be inaccurate for Hib and PCV7. Despite 91.5% of caregivers stating that shots
      were up-to-date, only 66.0% were correct that their child was up-to-date with
      these 2 vaccines. The ED physician should use caution in making clinical
      decisions based on the history given by a caregiver regarding their child's
      immunization status.

PMID- 17505269
TI  - Epidemiology and outcome analysis of 208 children with burns attending an
      emergency department.
AB  - OBJECTIVE: The purpose of this study was to prospectively study all burns
      attending a single inner city emergency department (ED) to establish
      epidemiological burn patterns and final outcomes for thermal injuries affecting
      children. DESIGN AND SETTING: A 12-month prospective study of all burns involving
      children (ages, 0-16 years) presenting to a single ED serving approximately
      500,000 people. RESULTS: Two hundred eight children with burns attended the ED.
      The average patient age was 5 years, with most cases involving infants and young
      children. Fifty one percent of injuries were scalds, and 36% were contact burns.
      Burn size varied from 1% body surface area to 23% body surface area. First aid
      had not been administered in one third of cases before attendance, and 87% of
      patients had received no analgesia. Final outcomes were as follows: 5% of
      patients were discharged from the ED with no further follow-up. Twenty three
      percent of patients were instructed to attend their general practitioner for
      follow-up, and 58% were instructed to attend the ED clinic for review. Four
      percent of patients were reviewed in the plastic surgery dressing clinic, 7% were
      admitted to the plastic surgery ward, and 3% of patients were transferred to a
      burn center. In total, 3% of patients required burn excision and skin grafting
      for their burns. There were no deaths. CONCLUSIONS: Many pediatric burns are
      appropriately managed in the ED without the need for burn center care. Although
      the mortality from burn injury in children may have fallen in recent decades,
      problems persist in terms of small burns that can be associated with long
      standing morbidity. Education and prevention programs are still required at all
      levels to help address the problem of childhood burns.

PMID- 17505270
TI  - Age limits and transition of health care in pediatric emergency medicine.
AB  - OBJECTIVE: To describe the practice reported by pediatric emergency department
      (PED) medical directors regarding age limits and transition of health care in
      their emergency departments and institutions. METHODS: A 28-question survey was
      sent by e-mail to 116 PED medical directors. Descriptive statistics were used to
      report results; chi tests were used for comparing categorical data. RESULTS: The
      survey was completed by 73 PED medical directors (63%). Age-limit policies were
      present in 58 (79%) of the PEDs, and 56 reported a specific age. The 18th and
      21st birthdays were the most common specific ages cited. Thirty-six PEDs (64%)
      had an age limit of younger than 21 years. Pediatric emergency departments with
      age limits of 21 years or older versus younger than 21 years had a significantly
      higher rate of being associated with freestanding children's hospitals (P =
      0.037). Appropriate exceptions to the age-limit policy included patients both
      over and under the age limit. The most common overage limit exception was cystic
      fibrosis, and the most common underage limit exception was teenage pregnancy.
      Thirteen PED medical directors (18%) were aware of a transition-of-care
      (pediatric to adult care provider) policy or work group at their institution, and
      47 (64%) thought that such a work group would be valuable to addressing
      transition-of-care issues. CONCLUSION: In pediatric emergency medicine, the age
      of transition from pediatric to adult emergency care providers is variable both
      between and within institutions. Most PEDs have age limits of younger than 21
      years. Most PED medical directors support a multidisciplinary work group or
      committee as a method of addressing transition of care. Known barriers to
      transition of care previously reported in the literature are reviewed.

PMID- 17505271
TI  - Urine specific gravity and other urinary indices: inaccurate tests for
      dehydration.
AB  - OBJECTIVE: Urine output, specific gravity, and ketones (urinary indices) are
      commonly used as an objective means to assess for dehydration and gastroenteritis
      severity; however, their utility has not been established. The study was designed
      to evaluate the accuracy of urinary indices as diagnostic tests to identify acute
      dehydration. METHODS: We completed a prospective cohort study in the Emergency
      Department of an urban pediatric hospital. Seventy-nine subjects ages 3 months to
      36 months with gastroenteritis, clinically suspected moderate dehydration, and
      the need for intravenous rehydration were enrolled in the trial. Urine specific
      gravity and urine ketone levels were determined with bedside calorimetric
      (dipstick) testing, and urine output during rehydration and observation was
      measured by commonly used techniques. An internally validated, weight-based
      criterion standard for the percent dehydration on enrollment was used to identify
      the cohort of dehydrated subjects. Correlation statistics were calculated for
      urine output, specific gravity, and ketones. In addition, multilevel tables were
      created to determine the sensitivity, specificity, and likelihood ratio at
      varying test cutoff values to detect 3% and 5% dehydration. RESULTS: Urine
      specific gravity (r = -0.06, P = 0.64), urine ketones (r = 0.08, P = 0.52), and
      urine output during rehydration (r = 0.01, P = 0.96) did not correlate with the
      initial degree of dehydration present. Clinically useful cutoff values for urine
      specific gravity and ketones to increase or decrease the likelihood of
      dehydration at the time of enrollment could not be identified. CONCLUSIONS:
      Urinary indices are not useful diagnostic tests to identify the presence of
      dehydration during the initial assessment of children with gastroenteritis.

PMID- 17505273
TI  - Skeletal surveys in children with burns caused by child abuse.
AB  - OBJECTIVE: To determine the frequency of occult fractures in children with
      suspicious burns compared with children with other types of physical abuse.
      METHODS: Child abuse outpatient clinic reports and inpatient consultations from a
      midwest urban children's hospital for 1989 to 2000 were reviewed. Demographic and
      clinical data were abstracted for patients seen because of suspected physical
      abuse. Patients were classified based on reason seen (burns vs other physical
      injuries), whether they were diagnosed as abused, and whether they had at least 1
      skeletal survey. Positive skeletal surveys were defined as having a fracture that
      was unexplained, highly specific for abuse, or with a perpetrator confession.
      RESULTS: Of 335 patients evaluated, the mean age (+/-SD) was 1.5 +/- 1.9 years,
      63% were boys, 64% were white, and 80% had skeletal surveys performed. Reasons
      for evaluation included 69 (21%) for burns and 266 (79%) for other injuries.
      After excluding patients without a final diagnosis of abuse and those presenting
      with obvious fractures, 5 (14%) of 36 burn patients had positive skeletal surveys
      compared with 45 (34%) of 133 with nonburn injuries (P = 0.02). Burn patients
      were older compared with those with nonburn injuries (mean ages, 1.8 +/- 1.5 vs.
      1.1 +/- 1.6 years; P = 0.03) and were more likely to be nonwhite (69% vs. 32%; P
      < 0.001). CONCLUSIONS: Although young children with abusive burns have fewer
      occult fractures compared with those with other abusive injuries, the frequency
      of occult fractures is still high enough to warrant the consideration of skeletal
      surveys in these cases.

PMID- 17505272
TI  - Job market survey of recent pediatric emergency medicine fellowship graduates.
AB  - OBJECTIVES: The American Academy of Pediatrics Section of Emergency Medicine's
      Subcommittee on Administration developed a survey tool targeting recent pediatric
      emergency medicine (PEM) fellowship graduates to assess the current PEM job
      market in a variety of areas including (1) the new positions accepted, (2)
      perspectives of fellowship training, and (3) the relationship between PEM and
      general emergency medicine practice. METHODS: The 40-question internet-based
      survey was developed through www.surveymonkey.com. Solicitations to PEM
      fellowship graduates who completed training between the years 2000 and 2005 were
      sent via the Section of Emergency Medicine member e-mail list as well as the PEM
      LISTSERV. Data collection occurred from April to May 2005. RESULTS: Of 125 survey
      respondents, 89% completed a 3-year pediatrics residency plus a 3-year PEM
      fellowship. Offers to graduates of positions with research expectations
      outnumbered clinical positions, 3:2, with an average of 5 total positions offered
      per respondent. Thirty-four percent remained at the institution of fellowship
      graduation, and 71% accepted faculty appointments with medical school
      affiliation. Seventy percent of work time was spent on clinical duties and 10% on
      research. Most felt better prepared in the areas of clinical training and
      teaching than in the areas of research and administration. Additional general
      emergency medicine exposure was not desired. Half of the respondents felt that a
      2-year fellowship program would have met their career goals. CONCLUSIONS: Recent
      PEM fellowship graduates felt that job availability was good and were satisfied
      with their new positions. Respondents perceived better fellowship training in
      clinical and teaching aspects than in research and administration. New positions
      were heavily clinical and matched career goals.

PMID- 17505274
TI  - Acute colchicine intoxication in a child: a case report.
AB  - Colchicine poisoning is an uncommon, but potentially life-threatening,
      toxicologic emergency. The clinical features associated with overdose and the
      options for treatment are discussed. Colchicine poisoning typically shows 3
      phases: initially, gastrointestinal symptoms predominate; in the second phase,
      multiorgan failure may occur, possibly leading to death. If the patient survives,
      the third phase of recovery follows, during which the patient often presents with
      hair loss. Early fatality is due to cardiovascular collapse and respiratory
      failure; however, pancytopenia and overwhelming septicemia can occur later. All
      patients suspected of having colchicine intoxication because of its unpredictable
      outcome should be managed according to the principles of intensive care,
      irrespective of the actual degree of poisoning. In those patients who survive the
      initial phase of poisoning, filgrastim (granulocyte colony-stimulating factor)
      offers an effective method of treating pancytopenia and preventing overwhelming
      septicemia. Daily monitoring of the patients' hematological status is strongly
      recommended. We are reporting a case of previously healthy girl who developed a
      multisystem organ failure after colchicine intoxication. The patient recovered
      completely and had no residual outcome.

PMID- 17505275
TI  - Bullous impetigo: a rare presentation in fulminant streptococcal toxic shock
      syndrome.
AB  - Since the mid-1980s, an increase in incidence of invasive disease caused by group
      A streptococci has been noted among adults and children. The characteristic
      clinical and laboratory features of the streptococcal toxic shock syndrome
      include deep-seated infection associated with shock, skin manifestation, and
      multiorgan failure. However, bullous impetigo is invariably considered to be a
      staphylococcal disease. Staphylococcus aureus produces an epidermolytic toxin,
      assumed to be the cause of bullous formation in the skin. Here, we present a case
      of bullous impetigo in an infant with streptococcal toxic shock syndrome. This is
      a rare presentation of bullous impetigo caused by group A streptococcus.

PMID- 17505276
TI  - A 6-month old with total body flushing and a macular-papular lesion.
AB  - Flushing of the skin of an infant may be a sign of the child's first allergic
      reaction to food, insect envenomation, or other allergens, a sign of sepsis, or
      due to dilation of cutaneous vessels caused by a vasodilator substance or neural
      mechanisms. A rare cause of this condition results in the release of mast cell
      mediators such as histamine, prostaglandin D2, tryptase, chymase, and
      leukotrienes. We present a case of a 6-month-old with severe total body flushing
      and a yellow-tan, raised, well-demarcated lesion on the thigh consistent with a
      solitary mastocytoma. Erythema was most pronounced adjacent to the lesion,
      suggesting a positive Darier sign. Subsequent evaluation by a dermatologist
      confirmed the diagnosis, and the patient underwent no further therapy; however,
      the family was appropriately counseled on management if the symptoms were to
      reappear. Appropriate diagnosis and management of this patient and other forms of
      mastocytosis in children are discussed.

PMID- 17505277
TI  - Group B streptococcal cellulitis in infancy.
AB  - Cellulitis in an infant younger than 3 months is most commonly caused by group B
      streptococci (GBS). A baby with cellulitis in this age group should have a full
      septic workup including blood and cerebrospinal fluid cultures, as GBS cellulitis
      may be associated with bacteremia. We discuss a 6-week-old baby with cellulitis
      and meningitis to illustrate the potential complexity of this infectious disease
      process. We also present a concise review of GBS cellulitis and of meningitis
      with initially normal cerebrospinal fluid analysis.

PMID- 17505278
TI  - Congenital malaria, an important differential diagnosis to consider when
      evaluating febrile infants of immigrant mothers.
AB  - Congenital malaria is reported rarely in the United States and almost exclusively
      affects infants of immigrant mothers. Because of its nonspecific presentation
      with fever during the first 3 months of life, it is an important differential
      diagnosis when evaluating such infants with fever in the pediatric emergency
      department. A complete and accurate travel and residency history on the infant's
      family should be sought during evaluation. As intercontinental travel and
      immigration increases, emergency department physicians should be alert to the
      diagnosis of malaria in ill neonates and young infants. We discuss a case of
      congenital malaria in a 26-day-old infant and review the clinical features of
      previously reported cases in the United States.

PMID- 17505279
TI  - Pleural effusions.
AB  - The ability to recognize, understand, and treat pleural effusions in the
      pediatric population is important for pediatric health care providers. The topic
      of pleural effusions has been extensively studied in the adult population. In
      recent years, these studies have extended into the pediatric population. This
      review describes pleural effusions in detail, including the different types and
      underlying pathophysiology. We then go on to provide a comprehensive review of
      the recent literature regarding the diagnosis and treatment of pleural effusions
      in the pediatric population.

PMID- 17505281
TI  - Absorbable versus nonabsorbable sutures in the management of traumatic
      lacerations and surgical wounds: a meta-analysis.
AB  - OBJECTIVES: To complete a systematic review of randomized controlled trials
      (RCTs) that compare the cosmetic outcomes and complications of traumatic
      lacerations and surgical incisions closed with absorbable sutures versus
      nonabsorbable sutures. DESIGN/METHODS: We searched MEDLINE, EMBASE, and Cochrane
      Central to identify all RCTs comparing absorbable versus nonabsorbable sutures
      that assessed cosmetic outcomes or complications. Reference lists of all
      identified trials were also searched. Two independent reviewers screened
      abstracts for eligibility, extracted study data, and assessed trial quality.
      Disagreements were resolved by consensus or a third party. RESULTS: Three hundred
      thirty-eight citations were retrieved, of which 7 met inclusion criteria. Studies
      were heterogeneous with respect to specific interventions and outcome measures;
      sample sizes ranged from 44 to 166. There was no statistically significant
      difference between absorbable and nonabsorbable sutures in short- or long-term
      cosmetic score, scar hypertrophy, infection rate, wound dehiscence, and wound
      redness/swelling. CONCLUSIONS: Our meta-analysis suggests a lack of large,
      methodologically sound RCTs evaluating the effectiveness of absorbable versus
      nonabsorbable sutures. Although our analysis demonstrates that nonabsorbable
      sutures seem to be no better than absorbable sutures in the management of wound
      repair, a large methodologically sound RCT is needed to adequately answer this
      question.

PMID- 17505282
TI  - Apnea in an infant: what should I look for?

PMID- 17505283
TI  - ECGs in the ED.

PMID- 17505284
TI  - Pediatric emergency medicine: legal briefs.

PMID- 17505285
TI  - Erratum in intravenous n-acetylcysteine dosing.

PMID- 17505286
TI  - Diagnosis.

PMID- 17505288
TI  - Concurrent validity of the Early Intervention Developmental Profile and the
      Peabody Developmental Motor Scale-2.
AB  - PURPOSE: The purpose of this study was to determine the concurrent validity of
      the Early Intervention Developmental Profile (EIDP) and the Peabody Developmental
      Motor Scale-2 (PDMS-2) in examining gross motor delay. METHODS: Thirty children
      with a variety of developmental delays attending an early intervention program
      were administered both the PDMS-2 and the EIDP as part of their developmental
      evaluations. RESULTS: The PDMS-2 and EIDP were strongly correlated (r = 0.91, p <
      0.01) but the mean age equivalent scores were significantly different. Age
      equivalent scores were on average 26% higher on the EIDP. CONCLUSIONS:
      Differences in age equivalent scores between tests may affect a child's
      eligibility for services in some states. This study supports the use of norm
      based tests when determining a percentage of delay relative to the norm.
      Developmental tests should not be the sole determinant of the clinical decision
      making processes.

PMID- 17505287
TI  - Reliability for running tests for measuring agility and anaerobic muscle power in
      children and adolescents with cerebral palsy.
AB  - PURPOSE: We investigated reliability, construct validity, and feasibility of two
      sprint tests for children with cerebral palsy (CP). METHODS: Twenty-six children
      with CP participated (7-18 years of age; Gross Motor Function Classification
      System [GMFCS] level I or II). On different occasions, the 10 x 5-Meter Sprint
      Test and the Muscle Power Sprint Test were scored by different assessors.
      RESULTS: Excellent interobserver reliability (intraclass correlation [ICC] = 1.0
      and ICC >or= 0.97) and test-retest reliability (ICC = 0.97 and ICC >or= 0.97)
      were obtained. Scores differed significantly on both sprint tests for children
      classified at GMFCS level I and level II. Mean scores for feasibility ranged from
      8.8 to 9.2 on a 10-cm visual analog scale (10 = the best). CONCLUSIONS: Both
      exercise tests are reliable and have good feasibility for children and
      adolescents with CP (GMFCS level I or II). Construct validity is supported for
      both sprint tests in children classified at GMFCS level I and level II.

PMID- 17505290
TI  - Can exercise influence low bone mineral density in children with juvenile
      rheumatoid arthritis?
AB  - PURPOSE: Low bone mineral density (BMD) is a common secondary condition
      associated with juvenile idiopathic arthritis (JIA). The purpose of this review
      was evaluate the literature pertinent to designing an effective, safe weight
      bearing exercise program to reduce the risk of low BMD in children with JIA.
      SUMMARY OF KEY POINTS: Thirty-seven articles on the risk of low BMD and children
      with JIA, weight-bearing interventions to improve BMD in healthy children, or
      safety and efficacy of exercise interventions with children with JIA were
      critiqued on the basis of their design. Three highly rated studies confirmed the
      multifactorial nature of low BMD in children with JIA, two highly rated studies
      support the efficacy of weight-bearing interventions for increasing BMD in
      children who are healthy, and one moderately rated study demonstrated the safety
      of low impact exercise by children with JIA. STATEMENT OF CONCLUSIONS AND
      RECOMMENDATIONS FOR CLINICAL PRACTICE: Weight-bearing activities should be
      included in exercise programs for individuals with JIA, although more research is
      needed to determine the amount, duration, and frequency of weight-bearing
      activity needed to reduce the risk for low BMD.

PMID- 17505289
TI  - Program evaluation of physical therapy as an early intervention and related
      service in special education.
AB  - PURPOSE: The primary purpose of this study was to develop a database method for
      documenting achievement of Individualized Education Plan/Individualized Family
      Service Plan objectives in a practical and cost-effective manner that could be
      easily replicated in other school systems. METHOD: This study was conducted in a
      public school district in a Midwest metropolitan area in which 18 pediatric
      physical therapists provided services. A database method for documenting
      achievement of Individualized Education Plan/Individualized Family Service Plan
      objectives was used. The objectives of 566 children receiving physical therapy
      services were extracted from the records. A total of 2228 objectives were
      obtained for analysis. RESULTS: Ninety-one percent of the objectives were scored
      as met or progress made. Factors associated with achievement of objectives
      included the amount and type of service provided, program features, and
      attributes of the objective. CONCLUSION: A program evaluation methodology for
      physical therapy services in the educational setting is documented for others to
      replicate.

PMID- 17505291
TI  - Physical therapy intervention for an adolescent with a knee flexion contracture
      and diagnosis of multiple pterygium syndrome.
AB  - PURPOSE: The purpose of this case report is to describe a course of physical
      therapy for a client with a rare genetic condition, multiple pterygium syndrome
      (MPS). SUMMARY OF KEY POINTS: MPS is a rare genetic disorder characterized by
      connective tissue webbing across multiple joints, dysmorphic facies, and various
      visceral and skeletal deformities. Before the patient commenced physical therapy,
      surgical amputation was recommended for the client's knee flexion contracture.
      The client's treatment plan included stretching, manual therapy, and resisted
      exercise. Long-term outcomes were decreased back and knee pain and improved range
      of motion, strength, and ambulation. CLINICAL RECOMMENDATIONS: Therapists using
      techniques to improve joint range of motion in clients with MPS should be aware
      that pterygia may include contractile tissue, nerves, and blood vessels and there
      may be underlying skeletal deformity or weakness in these areas. Children with
      MPS are at high risk of developing scoliosis and should be appropriately assessed
      in early childhood.

PMID- 17505292
TI  - Gross motor development of Asian and European children on four motor assessments:
      a literature review.
AB  - PURPOSE: The purpose of this article is to review the evidence surrounding
      similarities and differences in motor development in children of Asian and
      European ethnic backgrounds to ensure the appropriateness of mixed ethnicity
      normative comparison data. SUMMARY OF KEY POINTS: A review of published studies
      indicates variability in rate and possibly sequence of motor development in
      children of European and Asian origins. STATEMENT OF CONCLUSIONS AND
      RECOMMENDATIONS FOR CLINICAL PRACTICE: Assessment tools used to discriminate
      motor development in children of different ethnic backgrounds should be
      interpreted with caution until there is sufficient information regarding the
      appropriateness of comparisons among children of different ethnic origins.

PMID- 17505293
TI  - Use of groups in pediatric physical therapy: survey of current practices.
AB  - PURPOSE: This nationwide survey study aimed to examine the use of groups in
      pediatric physical therapy, including characteristics, effectiveness, and
      financial considerations of group intervention. METHODS: Questionnaires were
      mailed to 500 randomly selected members of the American Physical Therapy
      Association Section on Pediatrics. Respondents reported on the characteristics of
      children typically included in group intervention, types of activities used,
      effectiveness at meeting goals, billing methods, and documentation practices.
      RESULTS AND CONCLUSIONS: The response rate was 285 (57%). Only 41.4% of
      respondents reported using groups. Characteristics of group intervention were
      variable among respondents, and considerable differences in billing practices and
      perceived effectiveness were noted. Commonly reported characteristics included
      use of small groups of young children with developmental delay and use of task
      specific developmental activities. Perceived benefits and limitations of group
      intervention were also reported. Implications for further research into the use
      of groups were explored.

PMID- 17505294
TI  - Heart rate response to therapeutic riding in children with cerebral palsy: an
      exploratory study.
AB  - PURPOSE: The study was designed to document the heart rate response to
      therapeutic riding in children with cerebral palsy having mild-to-severe
      disability. METHODS: Participants consisted of eight youth riders with cerebral
      palsy, divided into two groups: ambulatory and wheelchair dependent. The riders
      received continuous digital heart rate monitoring during 10 weekly 20-minute
      therapeutic horseback riding sessions. RESULTS: The averaged resting, median, and
      peak heart rate values, as well as the peak percentage heart rate reserve values,
      were significantly higher in the wheelchair-dependent group. CONCLUSIONS: The
      youth with severe disability (The Gross Motor Function Classification System
      level IV) who were wheelchair dependent demonstrated higher heart rate values
      during therapeutic riding than their ambulatory counterparts. In view of these
      higher heart rate values, further studies are needed to address the role of
      monitoring heart rate response during therapeutic riding.

PMID- 17505297
TI  - The X-files of inflammation: cellular mosaicism of X-linked polymorphic genes and
      the female advantage in the host response to injury and infection.
AB  - Females as compared with males display better general health status, longevity,
      and improved clinical course after injury and infection. It is generally believed
      that the female advantage is associated with the effects of sex hormones. This
      review argues that the sex benefit of females during the host response is
      associated with polymorphism of X-linked genes and cellular mosaicism for X
      linked parental alleles. Cells from females carry both parental X chromosomes
      (maternal, Xm; or paternal, Xp), whereas males carry only one (Xm). Because of
      dosage compensation and random X inactivation, half of the cells from females
      express either Xm or Xp. Therefore, females are cellular mosaics for their X
      linked polymorphic genes. This cellular mosaicism in females represents a more
      adaptive and balanced cellular machinery that is advantageous during the innate
      immune response. Several genes encoding key metabolic and regulatory proteins
      reside on the X chromosome, including members of the apoptotic cascade, hormone
      homeostasis, glucose metabolic enzymes, superoxide-producing machinery, and the
      toll-like receptor/nuclear factor kappaB/c-Jun N-terminal kinase signaling
      pathway. Polymorphic forms of these X-linked proteins are likely to manifest in
      phenotypic differences in the mosaic cell populations in females and may
      contribute to sex-related differences in the host response to injury and
      infection. The unique inheritance pattern of X-linked polymorphisms and their
      potential confounding effects in clinical trials are also discussed; furthermore,
      we present potential biomarkers for studying mosaic cell populations of innate
      immunity.

PMID- 17505298
TI  - When to include polymyxins in the empirical antibiotic regimen in critically ill
      patients with fever? A decision analysis approach.
AB  - We sought to approach a practical question: Should polymyxins be used in the
      initial empirical antibiotic regimen in the intensive care unit (ICU) patient
      with fever that is thought to be due to infection? By retrieving data from the
      literature and the WHONET Greece, we formulated a mathematical model to estimate
      the probability (Ptotal) that a gram-negative bacterium susceptible only to
      polymyxins is isolated from an ICU patient. Ptotal = P1 * P2 * P3 * P4, where
      Ptotal = total probability; P1 = probability that fever is due to infection; P2 =
      probability that infection is due to gram-negative bacteria; P3 = probability
      that the gram-negative bacterium is Acinetobacter baumannii, Pseudomonas
      aeruginosa, or Klebsiella pneumoniae; and P4 = probability that A. baumannii, P.
      aeruginosa, or K. pneumoniae is susceptible only to polymyxins. Using the
      information from our data sources, we estimated that P1 (before physician input
      in differential diagnosis) = 0.5, P2 = 0.523, P3 = 0.79, and P4 = 0.567, thus
      Ptotal = P1 * P2 * P3 * P4 = 0.5 * 0.523 * 0.79 * 0.567 = 0.117 = 11.7%. Based on
      this information and combining it with data regarding the attributable mortality
      of inappropriate empirical antimicrobial treatment, 4 to 5 patients in every 100
      ICU patients will die if physicians do not include polymyxins in the initial
      empirical regimen in the ICU setting for an episode of fever due to infection.
      Polymyxins should probably be included in the empirical antibiotic regimen in the
      ICU setting in hospitals, where the observed probability that a gram-negative
      bacterium (A. baumannii, P. aeruginosa, or K. pneumoniae) is polymyxin-only
      susceptible is close to that (50%) used in our model (based on the individual
      hospital data).

PMID- 17505299
TI  - Biphasic elevation in cerebrospinal fluid and plasma concentrations of endothelin
      1 after traumatic brain injury in human patients.
AB  - Severe traumatic brain injury (TBI) is characterized by a high mortality and poor
      outcome. The pathomechanisms involved are cytokine-mediated proinflammatory and
      anti-inflammatory reactions and significant cerebral microcirculatory disorders.
      The role of endothelin 1 (ET-1), a very potent vasoconstrictive peptide, in the
      deterioration of cerebral perfusion after trauma is still unclear. The presented
      study investigated the changes in ET-1 in the cerebrospinal fluid (CSF) and
      plasma after TBI in humans, with special regard to the presence of subarachnoid
      hemorrhage (SAH) and clinical outcome. Twenty patients with TBI were
      consecutively enrolled into the study, 10 patients without SAH (TBI group) and 10
      patients with SAH (TBI-H group). Paired samples of plasma and CSF were collected
      for 10 days after trauma. Analysis of the ET-1 concentrations showed that TBI is
      associated with initially increased ET-1 values in plasma (TBI, day 1; TBI-H,
      days 2-3) and significantly increased (P < 0.05, vs. control) CSF concentrations
      (TBI, days 1-2; TBI-H, days 1-3) in the first days after trauma. In the further
      time course, ET-1 values declined in both groups, reaching reference values in
      plasma. The CSF values remained significantly (P < 0.05 vs. control) elevated.
      Both groups showed a second peak on the beginning of the second week after trauma
      in plasma and CSF. Whereas plasma concentrations failed to reach significance,
      CSF values showed a significant peak on day 7 in both groups. The TBI-H patients
      had significantly (P < 0.05) higher values in the secondary peak compared with
      patients of the TBI group. The kinetics of traumatic SAH-dependent ET-1 needs to
      be assessed in further investigations.

PMID- 17505300
TI  - A prospective randomized trial comparing oxygen delivery versus transcutaneous
      pressure of oxygen values as resuscitative goals.
AB  - Transcutaneous pressure of oxygen (PtcO2) correlates with arterial pressure of
      oxygen (PaO2) in nonshock states, but in shock states, PtcO2 approximates cardiac
      output with no response to increasing fraction of inspired oxygen (FiO2) and
      PaO2. An incremental change of more than 21 mmHg in PtcO2 in response to an FiO2
      of 1.0 (identified as the oxygen challenge test [OCT]) implies adequate tissue
      perfusion, and lack of response has been associated with mortality. Patients with
      severe sepsis and septic shock requiring pulmonary artery catheters were
      randomized to two groups: the oxygen delivery (DO2) group was treated to a DO2
      and mixed venous oxygen saturation goals, and the PtcO2 group was treated to
      achieve an OCT value of 40 mmHg or more. The DO2 (n = 30) and PtcO2 (n = 39)
      groups were similar in baseline characteristics. Mortality rate was 12 (40%) of
      39 for the DO2 group and 5 (13%) of 39 for the PtcO2 group (P = 0.02). Logistic
      regression analysis of the statistically significant variables between survivors
      and nonsurvivors demonstrated that inability to reach the PtcO2 goal at 24 h
      after resuscitation (T24) and a positive cardiac history are associated with
      mortality (P < 0.001). The area under the receiver operating curve was 0.824 for
      the OCT at T24. The best OCT value was 25 mmHg at T24 with positive and negative
      predictive values of 87% and 90%, respectively. Treating patients with severe
      sepsis/septic shock to an OCT value of 25 mmHg or more may provide a specific end
      point of resuscitation that may be associated with better survival than
      resuscitating to the central hemodynamic parameters of DO2 and mixed venous
      oxygen saturation.

PMID- 17505302
TI  - The effects of the fibrin-derived peptide Bbeta(15-42) in acute and chronic
      rodent models of myocardial ischemia-reperfusion.
AB  - Many compounds have been shown to prevent reperfusion injury in various animal
      models, although to date, translation into clinic has revealed several obstacles.
      Therefore, the National Heart, Lung, and Blood Institute convened a working group
      to discuss reasons for such failure. As a result, the concept of adequately
      powered, blinded, randomized studies for preclinical development of a compound
      has been urged. We investigated the effects of a fibrin-derived peptide Bbeta(15
      42) in acute and chronic rodent models of ischemia-reperfusion at three different
      study centers (Universities of Dusseldorf and Vienna, TNO Biomedical Research). A
      total of 187 animals were used, and the peptide was compared with the free
      radical scavenger Tempol, CD18 antibody, alpha-C5 antibody, and the golden
      standard, ischemic preconditioning. We show that Bbeta(15-42) robustly and
      reproducibly reduced infarct size in all models of ischemia-reperfusion.
      Moreover, the peptide significantly reduced plasma levels of the cytokines
      interleukin 1beta, tumor necrosis factor alpha, and interleukin 6. In rodents,
      Bbeta(15-42) inhibits proinflammatory cytokine release and is cardioprotective
      during ischemia-reperfusion injury.

PMID- 17505301
TI  - The priming effect of C5a on monocytes is predominantly mediated by the p38 MAPK
      pathway.
AB  - The dysregulation of the inflammatory response after trauma leads to significant
      morbidity and mortality. Monocytes and macrophages play a central role in the
      orchestration of the inflammatory response after injury. Serum interleukin-6 (IL
      6) concentration correlates with poor outcomes after injury. Tumor necrosis
      factor-alpha (TNF-alpha) is a proinflammatory cytokine that plays a crucial role
      in the pathogenesis of multiple organ dysfunction syndrome. Furthermore, in the
      presence of C5a, monocytes and macrophages have potentiated responses, but the
      mechanisms underlying this response remain largely unknown. Peripheral blood
      mononuclear cells (PBMCs) were isolated from healthy volunteers and pretreated
      with C5a (100 ng/mL) for 1 h before adding lipopolysaccharide (LPS) (10 ng/mL)
      for up to 20 h. Inhibitors for the mitogen-activated protein kinases (MAPKs) were
      added 1 h before adding C5a. C5a primes monocytes for LPS-induced IL-6 and TNF
      alpha production. Treatment of PBMCs with C5a leads to a rapid activation of the
      3 MAPK pathways. SP600125 (inhibitor of c-Jun NH2-terminal kinase MAPK) and
      PD98059 (inhibitor of extracellular signal-regulated kinase MAPK) did not affect
      the C5a priming of the LPS-induced IL-6 and TNF-alpha production, whereas
      SB203580, a specific inhibitor of p38 MAPK, did suppress the C5a priming effect.
      These results demonstrate that C5a primes adherent PBMCs and modulates LPS
      induced IL-6 and TNF-alpha production. Results from extracellular signal
      regulated kinase and c-Jun NH2-terminal kinase MAPK blockade suggest that these
      signaling pathways have minimal or no role in reprogramming LPS-mediated IL-6 and
      TNF-alpha production. On the contrary, in PBMCs, C5a activates the p38 cascade,
      and this pathway plays a major role in the C5a enhancement of LPS-induced IL-6
      and TNF-alpha production.

PMID- 17505303
TI  - Positive end-expiratory pressure does not compromise myocardial contractility in
      myocardial ischemia/reperfusion.
AB  - Therapy for severe myocardial ischemia/reperfusion sometimes necessitates
      intermittent positive pressure ventilation, which may impair left ventricular
      function by reduction of ventricular loading. It is unknown today whether
      positive airway pressure also affects contractile force after myocardial
      ischemia/reperfusion. The authors tested whether positive end-expiratory pressure
      (PEEP) impairs myocardial contractility in acute ischemic heart failure. In 11
      anesthetized mechanically ventilated pigs (28 +/- 3 kg), cardiac output (CO,
      aortic flow probe), load-independent parameters of left ventricular contractility
      (conductance method: preload recruitable stroke work [PRSW] and end-systolic
      elastance [E(es)]) and preload (end-diastolic volume [EDV] conductance) were
      assessed before and after myocardial ischemia and reperfusion (left anterior
      descending artery occlusion, 60 min). Data were taken during PEEP 0, 5, and 10 cm
      H2O. Before myocardial ischemia, both PEEP 5 and 10 cm H2O reduced CO (P < 0.05)
      because of a reduction of EDV (P < 0.05, PEEP 10 cm H2O). The PRSW remained
      unchanged (not significant [NS]) and E(es) increased (P < 0.05, PEEP 10 cm H2O).
      After myocardial ischemia/reperfusion, CO and PRSW, but not E(es) (NS),
      deteriorated markedly. At the same time, PEEP 10 cm H2O reduced CO (P < 0.05)
      and, slightly, EDV (NS). Now, both PRSW (P < 0.05, PEEP 5 cm H2O) and E(es) (P <
      0.05, PEEP 10 cm H2O) improved upon ventilation with PEEP. In our model, the
      administration of PEEP impaired global left ventricular function before and after
      myocardial ischemia/reperfusion. The observed impairment is not attributable to
      compromised contractility.

PMID- 17505304
TI  - Protection from hepatic ischemia/reperfusion injury and improvement of liver
      regeneration by alpha-lipoic acid.
AB  - The aim of this study was to characterize the in vivo action of lipoic acid (LA)
      in hepatic ischemia/reperfusion injury (IRI) and its effects on liver
      regeneration involving the investigation of mechanisms of action and effects on
      animal survival. Two groups of rats were compared: one group received 500
      micromol alpha-LA injected via the inferior vena cava 15 min before the induction
      of 90 min of selective ischemia. The untreated group received vehicle. Influence
      of LA on IRI of the liver was determined in short- and long-term experiments.
      Cellular damage was decreased under preconditioning conditions with LA. Caspase
      3, 8, and 9 activities were significantly lower in the LA group accompanied by a
      decrease in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      positive hepatocytes. Electron micrographs in the untreated group showed massive
      mitochondrial damage. The survival rate as end point of liver function was
      markedly increased after pretreatment with LA. Increased levels of tumor necrosis
      factor alpha was shown by enzyme-linked immunosorbent assay as well as real-time
      reverse transcription-polymerase chain reaction in the LA group accompanied by
      increased mitotic index and Ki-67 staining in liver tissue. Attenuation of IRI of
      the rat liver in vivo by LA is accompanied by reduction of necrosis and apoptosis
      related cell death, whereas liver regeneration is increased.

PMID- 17505306
TI  - Resuscitation with 21% or 100% oxygen is equally effective in restoring perfusion
      and oxygen metabolism in the liver of hypoxic newborn piglets.
AB  - The differential effects of the use of high or low oxygen levels during
      resuscitation on the neonatal liver are unknown. We compared the hepatic
      hemodynamics and oxygen metabolism in hypoxic newborn piglets resuscitated with
      21% or 100% oxygen. Twenty-seven piglets (age, 1-3 days; weight, 1.5-2.0 kg) were
      acutely instrumented to measure cardiac output, hepatic artery, and portal venous
      blood flows (hepatic artery flow index [HAFI] and portal venous flow index
      [PVFI], respectively). The animals underwent 2 h of hypoxia (fraction of inspired
      oxygen, 0.10-0.15), then reoxygenation with 21% (n = 9) or 100% (n = 9) oxygen
      for 1 h, then 1 h with 21% oxygen. The controls (n = 9) were sham-operated
      without hypoxia-reoxygenation. Oxygen transport and plasma lactate concentrations
      were studied. Hypoxic animals had hypotension and decreased cardiac index with
      metabolic acidosis (mean pH, 7.00-7.02; P < 0.05 vs. controls). The PVFI and the
      total hepatic blood flow (THFI = PVFI + HAFI), despite the absence of significant
      change in HAFI, decreased to 16 +/- 2 mL/min/kg and 19 +/- 3 mL/min/kg,
      respectively (versus 24 +/- 2 mL/min/kg and 28 +/- 2 mL/min/kg of controls; P <
      0.05). Fifteen minutes after reoxygenation, the cardiac index improved, PVFI
      recovered, HAFI was maintained, and THFI was not different between the groups.
      The hepatic oxygen consumption decreased (59%; P < 0.05) and the extraction
      increased (89%; P < 0.001) during hypoxia. Similarly, on reoxygenation, the
      hepatic oxygen consumption improved; however, extraction decreased versus
      controls on 100% but not on 21% oxygen (P < 0.05). The plasma lactate
      concentrations increased in both groups with hypoxia and were not different
      during reoxygenation between the group administered with 21% oxygen and the group
      administered with 100% oxygen. The hypoxic neonatal liver has reduced hepatic
      blood flow but has relatively preserved HAFI, and oxygen consumption recovered
      similarly on reoxygenation with 21% and 100% oxygen. The increased oxygen
      extraction during hypoxia normalized in 21% but reduced in 100% reoxygenation,
      with no differences in plasma lactate concentrations.

PMID- 17505305
TI  - Resuscitation from hemorrhagic shock with HBOC-201 in the setting of traumatic
      brain injury.
AB  - Outcomes after mild or moderate head trauma are worsened with associated
      hypotension, and secondary brain injury can be reduced with timely resuscitation.
      This study was performed to investigate HBOC-201 as a resuscitation therapy in a
      combined hemorrhagic shock and brain injury model. Anesthetized rats sustained
      moderate brain injury using a controlled cortical impact device, followed by
      rapid hemorrhage to a mean arterial pressure of 30 mmHg. After 30 min of
      hypotension, animals were resuscitated with HBOC-201, autologous shed blood (SB),
      or lactated Ringer solution (LR). Brain injury was assessed by measurements of
      cerebral blood flow (CBF) and cerebral vasoreactivity to hypercapnia (CVH) using
      a laser Doppler flowmeter. Contusion volume was evaluated histologically, and
      cerebral edema was determined by total water content. The HBOC rats required
      significantly less resuscitation volume versus LR and SB. The CBF was
      significantly diminished at 60 min after resuscitation with HBOC (70.1% +/- 3.8%
      baseline) compared with LR (105.8% +/- 10.1% baseline; P < 0.01) and SB (96.8% +/
      5% baseline; P < 0.05). The CVH was preserved in the HBOC and SB groups. The CVH
      was significantly diminished compared with baseline in the LR group at 30 min
      after resuscitation and showed a significant loss compared with HBOC at 60 min
      after resuscitation. The contusion volume for HBOC (45.1 mm3) and SB (35.1 mm3)
      was less than LR (63.5 mm3, P < 0.01). Although CBF was diminished after
      resuscitation in the HBOC group, HBOC-treated animals maintained CVH and
      experienced significantly smaller contusion volume than those treated with LR.
      These results suggest that resuscitation with HBOC-201 protects autoregulatory
      mechanisms and may reduce secondary brain injury in traumatic brain injury.

PMID- 17505307
TI  - Human umbilical cord blood-derived CD34+ cells cause attenuation of multiorgan
      dysfunction during experimental heatstroke.
AB  - Multiorgan dysfunction ensuing from severe heatstroke includes hypotension,
      hepatic and renal failure, hypercoagulable state, activated inflammation, and
      cerebral ischemia and injury. We attempted to assess whether human umbilical cord
      blood-derived CD34+ cell therapy improves survival during experimental heatstroke
      by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the
      onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+
      cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient
      temperature of 43 degrees C to induce heatstroke. Another group of rats were
      exposed to room temperature (26 degrees C) and used as normothermic controls.
      Hypotension, hepatic and renal failure (evidenced by increased serum urea
      nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and
      alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by
      increased prothrombin time, activated partial thromboplastin time, and D-dimer,
      and decreased platelet count and protein C in plasma), activated inflammation
      (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction
      (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and
      cerebral ischemia and injury) were monitored. When the CD34- cell-treated or
      untreated rats underwent heat stress, their survival time values were found to be
      19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time
      (duration, 63-291 min). As compared with normothermic controls, all CD34- cell
      treated heatstroke animals displayed hypotension, hepatic and renal failure,
      hypercoagulable state, activated inflammation, and cerebral ischemia and injury.
      However, CD34+ cell therapy significantly caused attenuation of all the above
      mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and
      glial cell line-derived neurotrophic factors in brain were all significantly
      increased after CD34+ cell therapy during heatstroke. Our data indicate that
      CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing
      multiorgan dysfunction or failure.

PMID- 17505308
TI  - Sodium butyrate prevents lethality of severe sepsis in rats.
AB  - This study was performed to investigate a novel strategy to pharmacologically
      inhibit high-mobility group box 1 protein (HMGB1) expression with sodium
      butyrate, a short-chain fatty acid. Using a sepsis model induced by cecal
      ligation and puncture (CLP), 100 male Wistar rats were randomly divided into 4
      groups as follows: control group (10 rats), sham operation group (10 rats), CLP
      group (further randomized into 2, 6, 12, 24, 48, and 72 h post-CLP subgroups,
      each 10 rats), and sodium butyrate treatment group (further randomized into 12
      and 24 h post-CLP subgroups, each 10 rats). Animals of all groups were killed at
      designated time points, and blood and tissue samples from livers, lungs, kidneys,
      and small intestines were harvested to determine organ damage-related variables,
      and HMGB1 mRNA expression was assessed by the reverse-transcription-polymerase
      chain reaction. In addition, we observed the effect of treatment with sodium
      butyrate on survival rate in septic rats. The results showed that early treatment
      with sodium butyrate can markedly reduce serum alanine aminotransferase,
      creatinine levels at 12 h, and pulmonary myeloperoxidase activity at 24 h post
      CLP, and significantly improve the 1- to 6-day survival rates in animals
      subjected to CLP (P < 0.05-0.01). These findings suggest that HMGB1 is
      excessively expressed and produced in sepsis. Sodium butyrate can markedly
      inhibit HMGB1 mRNA expression and may have protective effect on multiple organ
      damage in sepsis.

PMID- 17505309
TI  - CCK-8 inhibits LPS-induced IL-1beta production in pulmonary interstitial
      macrophages by modulating PKA, p38, and NF-kappaB pathway.
AB  - The neuropeptide cholecystokinin octapeptide (CCK-8) inhibits inflammation by
      downregulating the expression of proinflammatory cytokines, such as tumor
      necrosis factor alpha and interleukin (IL) 1beta during endotoxin shock. However,
      the signaling mechanism of CCK-8 action has not yet been clearly elucidated. In
      this study, we have examined the possible signaling pathways by which CCK-8
      inhibits lipopolysaccharide (LPS)-induced IL-1beta production in rat pulmonary
      interstitial macrophages. In macrophages, LPS is known to activate p38 kinase,
      which, in turn, activates nuclear factor (NF)-kappaB to induce IL-1beta
      production. We found that the pretreatment of cells with CCK-8 blocked the LPS
      induced p38 kinase, NF-kappaB activation, and IL-1beta production. Furthermore,
      CCK-8 treatment activated the cyclic adenosine monophosphate-protein kinase A
      signaling pathway and H-89 (a protein kinase A inhibitor), abrogated the
      inhibitory effects of CCK-8 on p38 kinase activation and NF-kappaB activation. In
      addition, we also demonstrate that the specific antagonist to CCK-1 receptor (CCK
      1R) and CCK-2 receptor (CCK-2R) abrogate the CCK action, and that the effects of
      the antagonist specific to CCK-1R is more significant. These results suggest that
      these responses were mediated through CCK-1R and CCK-2R, and CCK-1R might be the
      major receptor responsible for the anti-inflammatory effect of CCK-8. Taken
      together, our results indicate that the stimulation of cyclic adenosine
      monophosphate-protein kinase A signaling pathway by CCK-8 through CCK-1R and CCK
      2R inhibits the LPS-induced activation of p38 kinase and NF-kappaB to block the
      IL-1beta production in rat pulmonary interstitial macrophages.

PMID- 17505310
TI  - Cyclic adenosine monophosphate-phosphodiesterase inhibitors reduce skeletal
      muscle protein catabolism in septic rats.
AB  - We have previously shown that catecholamines exert an inhibitory effect on muscle
      protein degradation through a pathway involving the cyclic adenosine
      monophosphate (cAMP) cascade in normal rats. In the present work, we investigated
      in vivo and in vitro effects of cAMP-phosphodiesterase inhibitors on protein
      metabolism in skeletal muscle from rats submitted to a model of acute sepsis. The
      in vivo muscle protein metabolism was evaluated indirectly by measurements of the
      tyrosine interstitial concentration using microdialysis. Muscle blood flow (MBF)
      was monitored by ethanol perfusion technique. Sepsis was induced by cecal
      ligation and puncture and resulted in lactate acidosis, hypotension, and
      reduction in MBF (-30%; P < 0.05). Three-hour septic rats showed an increase in
      muscle interstitial tyrosine concentration (approximately 150%), in arterial
      plasma tyrosine levels (approximately 50%), and in interstitial-arterial tyrosine
      concentration difference (approximately 200%; P < 0.05). Pentoxifylline (50 mg/kg
      of body weight, i.v.) infusion during 1 h after cecal ligation and puncture
      prevented the tumor necrosis factor alpha increase and significantly reduced by
      50% (P < 0.05) the interstitial-arterial tyrosine difference concentration. In
      situ perfusion with isobutylmethylxanthine (IBMX; 10(-3) M) reduced by 40% (P <
      0.05) the muscle interstitial tyrosine in both sham-operated and septic rats.
      Neither pentoxifylline nor IBMX altered MBF. The addition of IBMX (10(-3) M) to
      the incubation medium increased (P < 0.05) muscle cAMP levels and reduced
      proteolysis in both groups. The in vitro addition of H89, a protein kinase A
      inhibitor, completely blocked the antiproteolytic effect of IBMX. The data show
      that activation of cAMP-dependent pathways and protein kinase A reduces muscle
      protein catabolism during basal and septic state.

PMID- 17505311
TI  - Optical spectroscopy demonstrates elevated intracellular oxygenation in an
      endotoxic model of sepsis in the perfused heart.
AB  - Recent clinical studies of patients with sepsis have shown that the delivery of
      adequate oxygen alone does not necessarily result in improved organ function or
      survival. This study was undertaken to determine if optical spectroscopy could
      detect higher intracellular oxygenations in isolated, perfused guinea pig hearts
      that have been treated with endotoxin (lipopolysaccharide [LPS]) than in
      controls. Four hours after intraperitoneal injection with LPS, adult guinea pigs
      were anesthetized, and hearts were excised and perfused in the Langendorff
      manner. Six control and eight LPS-exposed guinea pigs were studied. Myoglobin
      oxygen saturation was determined from analysis of optical reflectance spectra
      acquired from the left ventricular free wall. Myoglobin saturation was
      significantly higher at baseline with LPS than in controls (96.0% +/- 0.8% vs.
      89.4% +/- 1.7%, P < 0.001). At the end of 30 s of ischemia, myoglobin saturation
      decreased to 15% +/- 1% in controls, but to only 60% +/- 7% in the LPS group.
      Myocardial performance was determined by measured left ventricular developed
      pressure, which was significantly depressed in the LPS-exposed hearts relative to
      controls (30 +/- 4 mmHg vs. 67 +/- 9 mmHg, P < 0.001). Myocardial oxygen
      consumption, calculated from measurements of arterial and venous PO2 and coronary
      flow, was lower in LPS hearts relative to controls (0.199 +/- 0.021 mL oxygen x
      min(-1) x g(-1) vs. 0.157 +/- 0.006 mL oxygen x min(-1) x g(-1)). In this model
      of sepsis in the perfused guinea pig heart, intracellular oxygenation was higher
      and oxygen consumption was lower than in controls. Cellular dysfunction seen in
      sepsis may be caused by compromised oxygen use rather than insufficient oxygen
      delivery. Optical spectroscopy has the potential to noninvasively monitor
      patients and their responses to therapy.

PMID- 17505312
TI  - Continuously infused glipizide reverses the hyperdynamic circulation in ovine
      endotoxemia.
AB  - In advanced sepsis, hemodynamic support is often complicated by a tachyphylaxis
      against exogenous catecholamines. Although activation of adenosine triphosphate
      (ATP)-sensitive potassium (K(ATP)) channels plays a pivotal role in the
      pathogenesis of hyperdynamic vasodilatory shock, previous studies demonstrated
      only a transient increase in mean arterial pressure (MAP) after bolus
      administration of K(ATP) channel inhibitors. We hypothesized that a continuous
      infusion of the sulfonylurea glipizide, a K(ATP) channel inhibitor, may reverse
      cardiovascular dysfunctions in sepsis permanently. Eighteen adult sheep were
      instrumented for chronic study. After a baseline measurement in healthy ewes,
      endotoxin (Salmonella typhosa, 10 ng kg(-1) min(-1)) was continuously infused for
      19 h. After 16 h of endotoxemia, the surviving sheep (n = 14) were randomly
      assigned to be treated with either glipizide (5 mg/kg, followed by a continuous
      infusion of 8 mg kg(-1) h(-1)) or placebo (normal saline; each n = 7).
      Measurements of cardiopulmonary hemodynamics, global oxygen transport, acid-base
      status, and urine output were performed in the healthy state, after 16 h of
      endotoxemia, and during 3 h of glipizide infusion. Continuous infusion of
      glipizide reversed the endotoxin-induced hyperdynamic circulation, as indicated
      by significant increases in MAP and systemic vascular resistance index, as well
      as decreases in cardiac index and heart rate (P < 0.001 each). In addition,
      glipizide increased urine output as compared with untreated controls (P < 0.001).
      The anticipated decrease in glucose plasma levels was prevented by infusion of
      glucose 5%. From these results, we conclude that continuous glipizide infusion
      may represent a useful therapeutic option in the treatment of arterial
      hypotension related to sepsis and systemic inflammatory response syndrome.

PMID- 17505317
TI  - Current concepts on anatomy and biomechanics of patellar stability.
AB  - This review describes anatomic features of the patellofemoral joint that relate
      to the stability and function of the joint. The role of the geometry of the
      articular surfaces, particularly the trochlear groove, it's depth and
      orientation, are described. The stabilizing actions of the medial and lateral
      retinaculae, that tether the patella from either side to guide it into the
      trochlear groove in the early phase of knee flexion, are related to the specific
      structures, the medial patellofemoral ligament, and the fibers originating from
      the ilio-tibial tract laterally. The quadriceps muscles have different
      orientations, and converge onto the patella not only from either side but also
      from posteriorly, thus pulling the patella onto the anterior aspect of the
      trochlea. Finally, these local factors are discussed in relation to overall limb
      alignment, which leads to the mechanical logic of more extensive surgical
      procedures such as femoral rotational osteotomy or tibial tuberosity
      medialization.

PMID- 17505318
TI  - The role of lateral retinacular release in the treatment of patellar instability.
AB  - In the last 2 decades many authors have described the use of an isolated lateral
      retinacular release for the treatment of patellar instability. This review
      analyzes the published long-term results of this procedure for the treatment of
      patellar instability. The isolated use of a lateral retinacular release of the
      patella has not proven to be of long-term benefit for the treatment of patellar
      instability. It may be used as an adjunct procedure to a proximal or distal
      realignment of the extensor mechanism. Various pitfalls of a lateral release for
      patellar instability are discussed.

PMID- 17505319
TI  - Tibial tuberosity transfer for episodic patellar dislocation.
AB  - Numerous surgical techniques have been described to address episodic patellar
      dislocations. Some of them involve the soft tissues whereas others primarily
      address a bony correction. Four principal anatomic factors have been identified
      that increase the risk for episodic patellar dislocations: trochlear dysplasia,
      patella alta, patellar tilt, and an excessive tibial tubercle-trochlear groove
      distance. A treatment algorithm has been proposed to correct each of these
      factors. It includes the tibial tuberosity transfer, which is able to correct
      both a patella alta and an excessive tibial tubercle-trochlear groove distance.
      The tibial tuberosity can be transferred distally or medially or more frequently
      a combination of both. It will realign the extensor mechanism and increase
      patellofemoral stability. This procedure may be associated with a medial
      patellofemoral ligament reconstruction in case of excessive patellar tilt or
      rarely with a trochleoplasty for major abnormal patellar maltracking.

PMID- 17505320
TI  - Restoration of native medial patellofemoral ligament support after patella
      dislocation.
AB  - Much as the anterior talofibular ligament can be advanced to stabilize the
      lateral ankle, the healed, elongated medial patellofemoral ligament (MPFL) can be
      advanced to restore patellofemoral stability. We describe a simple technique
      whereby the MPFL remnant and femoral insertion can be easily identified and
      tested for integrity through a mini-open technique. In 13 consecutive cases after
      patellar dislocation, the MPFL was identified as a healed but elongated
      structure, with an intact, anatomically correct femoral insertion. Advancement of
      this healed, but elongated structure effectively restores stability in most
      patients. This helps in understanding why vastus medialis obliquus advancement
      has successfully restored patella stability in many patients after recurrent
      dislocation. MPFL advancement is an important alternative to full MPFL
      reconstruction in some patients.

PMID- 17505321
TI  - MPFL reconstruction.
AB  - The medial patellofemoral ligament has been recognized as the most important
      medial structure preventing lateral dislocation or subluxation of the patella.
      Numerous surgical techniques have been described to reconstruct this important
      structure in patients with patellofemoral instability. This paper reviews the
      relevant anatomy and biomechanics, published reconstruction options, and
      describes the surgical technique used at our institution using semitendinosus
      autograft to reconstruct the medial patellofemoral ligament.

PMID- 17505322
TI  - An algorithm guiding the evaluation and treatment of acute primary patellar
      dislocations.
AB  - Primary patellar dislocation continues to be a common problem facing clinicians
      today. These injuries are associated with significant morbidity and a substantial
      recurrence rate. A myriad of operative and nonoperative options have been
      described to treat these injuries though the evidence-based literature is sparse.
      As a result, much controversy exists regarding the ideal management of the
      primary patellar dislocation. This article reviews the literature on this topic,
      from the initial examination and management to definitive treatment. Furthermore,
      an algorithm is presented to help the clinician approach and treat these
      patients.

PMID- 17505323
TI  - Surgical options for patellar stabilization in the skeletally immature patient.
AB  - Patellar dislocations in children and youth are estimated to occur in 29 of
      100,000 individuals. Recurrent patellar dislocations in the skeletally immature
      patient are often associated with distinct pathoanatomies, which include patella
      alta, trochlear dysplasia, and contractures of the central and/or lateral
      structures of the extensor mechanism. This paper discusses the features of
      patellar instabilities classified as traumatic versus atraumatic, congenital
      versus acquired, and fixed dislocations versus habitual dislocations. Suggestions
      for the surgical management of these various classifications of patellar
      instabilities, on the basis of the principle of identification and correction of
      the pathoanatomies unique to the individual, are provided.

PMID- 17505324
TI  - Computational modeling: an alternative approach for investigating patellofemoral
      mechanics.
AB  - Computational modeling is commonly used in all engineering disciplines to
      represent complex systems. A computational model of the patellofemoral joint is a
      graphical representation of joint anatomy that can be manipulated to simulate
      knee function. Current models are typically reconstructed from magnetic resonance
      imaging scans of knees. Force vectors are applied to the patella to represent the
      quadriceps muscles, while the patella tendon is modeled with force vectors or
      deformable elements. Although the femur, tibia, and patella are typically modeled
      as rigid structures, the cartilage is represented with springs or modeled using
      finite element analysis. Computational models can be created to represent
      individual patients or general pathologic conditions. The quadriceps muscles and
      patella tendon can be manipulated to simulate patellofemoral pathology or
      surgical or nonsurgical treatment methods. The models can be used to characterize
      patellofemoral loading during knee flexion and characterize the distribution of
      force and pressure within the patellofemoral joint.

PMID- 17505325
TI  - Rehabilitation and nonoperative treatment of patellar instability.
AB  - Patellofemoral instability can be a difficult condition for clinicians to manage.
      Differentiation needs to be made as to whether the problem is an acute injury
      where a traumatic incident has usually precipitated the dislocation or whether
      the problem is a recurrent instability where the patellofemoral joint is unstable
      during everyday activities. This review defines instability, discusses the
      factors affecting instability, and provides assessment procedures and
      nonoperative intervention strategies for the clinician.

PMID- 17505326
TI  - Transoral laser marsupialization of epiglottic cysts.
AB  - OBJECTIVE: The objective of this study is to investigate the safety and
      effectiveness of laser marsupialization of epiglottic cysts via a transoral
      route. STUDY DESIGN: A prospective clinical series. METHODS: Twenty-eight
      consecutive patients with epiglottic cyst underwent laser marsupialization of an
      epiglottic cyst via a transoral approach. Pre- and postoperative laryngoscopic
      examinations were carried out. RESULTS: A total of 28 patients were enrolled,
      including 19 males and 9 females, ranging in age from 38 to 69 years, with a mean
      age of 54 years. Among these patients, 23 had a lumpy throat, and the remaining 5
      had a voice alternation. The diameters of the cysts ranged from 1 to 3 cm. No
      perioperative bleeding or airway swelling was noted in any patient. The
      postoperative follow-up period ranged from 4 to 41 (mean, 16) months. No
      recurrence was found during the follow-up examinations. CONCLUSION: Transoral
      laser marsupialization is a simple, safe, and effective method for treatment of
      epiglottic cysts. This procedure has the potential to serve as the treatment of
      choice in the management of this condition.

PMID- 17505328
TI  - Can primary care identify an 'at risk' group in the older population.
AB  - The promotion of health and independence for older people through preventative
      strategies is rising up the public health agenda in many countries and has been
      made a government policy objective in the UK. Despite forty years of
      experimentation, community nursing and general practice involvement in this field
      has been characterized by a lack of evidence to support broad screening and
      surveillance programmes and a failure to reach consensus on the most effective
      approaches to health promotion in later life. One initiative brought together
      community nursing, general practice and the voluntary social welfare sector in an
      inner urban setting to proactively identify and address unmet need and promote
      health through short term case management in an older population. This paper
      reports on the ability of the primary care teams to identify 'at risk' groups in
      the older population, which can then be targeted for comprehensive assessment.

PMID- 17505329
TI  - The use of a clinical algorithm for urinary catheterization.
AB  - Urinary catheterization is undertaken for a number of clinical conditions. Debate
      continues as to whether clinicians use catheters appropriately following thorough
      assessment or if they sometimes catheterize as it makes for easier clinical
      management. This article looks at the nursing process concerning safe and
      clinically relevant catheterization. PCTs have local algorithms for effective
      catheterization, an example of which is given here. Mention is made to the
      correct catheterization technique, with a look at commonly available catheter
      types.

PMID- 17505330
TI  - Accessible and integrated care: Scotland's community nursing review.

PMID- 17505331
TI  - Structured group-based education for type 2 diabetes in primary care.
AB  - To determine the effectiveness of structured group-based diabetes education
      programmes in improving glycaemic control in adults with type 2 diabetes in
      primary care a criteria-based review was conducted. The review of the three
      controlled trials identified showed that although HbA(1c) decreased in two of the
      studies, these differences were not statistically significant. Based on the
      present review, there is no evidence to recommend such programmes. However, due
      to limitations of these studies and opposing results of another trial not
      included in the review because of the uncertainty about criteria requirements
      caution is recommended in the interpretation of these findings.

PMID- 17505332
TI  - Case finding: a new approach to chronic disease prevention.
AB  - A working group of Specialist Nurses, Mental Health Nurses, DN Nurse
      Practitioners, and Community Development staff mapped the journey of a person
      identified with risk factors for chronic disease at a community health promotion
      event. The mapping exercise demonstrated that the GP was the main and only
      gatekeeper to a range of nursing and other services, and any health outcome
      depended upon the person seeking an appointment with the GP. Once a person was
      identified at an event, there was no follow up or mechanism of tracking the
      outcome.

PMID- 17505333
TI  - Pandemonium over painkillers persists.
AB  - Chronic non-cancer pain remains under-treated. Five years ago it was highlighted
      that more research was needed into the safety and efficacy of NSAIDs and opioid
      drugs in older people (Cowan, 2002). Concerns remain over NSAID-induced pathology
      and now there are safety concerns over the continued use of supposedly safer COX
      2 agents. There also remain concerns over the problematic use of opioids,
      including the potential for psychological and physical dependence. While more
      research is still needed to inform prescribing for older people, it is also
      apparent that we still need long-term studies of commonly used pain medications
      for the whole spectrum of age groups. Data derived from such studies would inform
      nurse prescribing.

PMID- 17505334
TI  - Older people's access to goods, facilities and services.
AB  - This article, brought to you in association with Help the Aged, highlights the
      problem of older people's access to goods, facilities and services and looks at
      how age discrimination impacts on it.

PMID- 17505335
TI  - Protecting children: the role of the law 2. Legal powers to safeguard children.
AB  - Last month's article on child protection considered the principles and key
      concepts that underpinned the approach to safeguarding children under the
      provisions of the Children Act 1989. This month Richard Griffith and Cassam
      Tengnah discuss the legal powers available under the Act that enable the proper
      authorities to intervene to protect children from significant harm.

PMID- 17505336
TI  - Provoking a debate.

PMID- 17505338
TI  - Tackling malnutrition among older people in the community.
AB  - Undernutrition - of both macronutrients and micronutrients - is still a
      surprisingly common problem among older people in the UK. There is a variety of
      nutritional supplements that community nurses need to be aware of in managing
      their patients' nutritional requirements. Different supplements are taken for
      different disease states. This article looks at the various nutrient and energy
      requirements that relate directly to clients on the district nurse's caseload.
      Some of the negative consequences of malnutrition of the older adult are
      discussed, as are the NICE guidelines for nutrition. Factors affecting dietary
      intake in older people are considered.

PMID- 17505340
TI  - Working with socially isolated older people.
AB  - This article, brought to you in association with Help the Aged, highlights the
      problem of social exclusion and loneliness and some of the issues of working with
      socially isolated older people.

PMID- 17505339
TI  - Screening for depression in older district nursing clients: feasibility study.
AB  - Depression is a common condition among older district nursing clients. This two
      cycle feasibility study trialled a process for depression screening by using the
      15-item Geriatric Depression Scale (GDS) with a sample of older clients in an
      Australian district nursing organization. An education session about depression
      and use of the GDS preceded the screening process. The trial found that a number
      of barriers existed among participant nurses regarding screening for depression,
      although generally they acknowledged depression as a common problem among older
      clients and most believed that they potentially had a important role in the
      identification and support of clients with this condition. Lack of knowledge
      emerged as a major constraint, as did uneasiness about entering the mental health
      area, with some reluctance to use the GDS because of the type of questions
      included and not wanting to be intrusive regarding the 'emotional matters' of
      clients. Recommendations are offered about screening for depression with this
      client population.

PMID- 17505341
TI  - The new Queen's Nurse: aims and benefits.

PMID- 17505342
TI  - How to face up to the spectre of redundancy.
AB  - Primary care trust (PCT) reconfigurations are now in their final phase. Posts
      have been deleted and staff who have not been slotted into other posts must apply
      for posts within their organization. Those who are unsuccessful must find posts
      elsewhere. This article aims to enable you to prepare for interview and to attain
      a new post.

PMID- 17505343
TI  - Protecting children: the role of the law 1. Principles and key concepts.
AB  - The twentieth anniversary of the Cleveland Child Abuse scandal provides a timely
      reminder that children continue to be abused and this generally occurs in the
      community perpetrated by family members or close acquaintances. District nurses
      have a significant role in the prevention and identification of child abuse as
      they visit families in their homes. Fundamental to this crucial role is a working
      knowledge of the provisions and concepts of the Children Act 1989 that sets out
      the legal framework for protecting children.

PMID- 17505344
TI  - Addressing the weight problem.

PMID- 17505345
TI  - Complex skin changes in chronic oedemas.
AB  - Skin changes can occur in an untreated or inadequately treated lymphoedematous
      limb over a period of time. These changes occur due to the chronic inflammation
      that is present in the limb, which increases the proliferation of connective
      tissue. The time it takes to develop these changes is different depending on the
      individual. Good skin care can significantly reduce the risk of these skin
      changes occurring. It is important to educate the patient as to the importance of
      maintaining a healthy, intact skin. This will significantly reduce the risk of
      these changes occurring. This article looks at the common skin changes found in
      lymphoedema, how to identify and treat them.

PMID- 17505346
TI  - Secondary lymphoedema: still poorly understood.

PMID- 17505347
TI  - Lymphorrhoea: 'leaky legs' are not just the nurse's problem.
AB  - Lymphorrhoea, the weeping of lymph through the skin, is a complication of chronic
      oedemas, and is generally poorly known or understood by the majority of nurses
      and doctors. It can occur not just in the legs, but also in other parts of the
      body affected by lymphoedema such as arms and axilla, chest and genitals. Using a
      case study to illustrate the key messages, this article discusses the management
      of lymphorrhoea and highlights the need for all health professionals to be more
      aware of this unpleasant and disruptive condition.

PMID- 17505348
TI  - The hidden epidemic.

PMID- 17505349
TI  - How to care for uncomplicated skin and keep it free of complications.
AB  - Many of the skin problems associated with lymphoedema and other chronic oedemas
      can be reduced or even prevented with appropriate and effective skin care. In
      particular, the use of emollients to maintain skin condition and integrity can
      reduce the frequency and severity of cellulitic episodes. This article describes
      best practice in the care of the skin in cases of uncomplicated lymphoedema.

PMID- 17505350
TI  - The Leg Club model in the Australian context.
AB  - Leg Clubs are an innovative approach to the holistic treatment of leg ulcers.
      They are run in a social context by community nurses who deliver ongoing support
      and treatment for a wide spectrum of lower limb pathology. This article looks at
      how the Leg Club model has been established in Australia.

PMID- 17505351
TI  - 'Look after your legs': patients' experience of an assessment clinic.
AB  - Venous leg ulcers are a chronic, recurring condition and a major cause of
      morbidity, especially in older people. Two inner city district nursing teams
      initiated a weekly, nurse-led, leg ulcer assessment clinic, and a monthly support
      group for patients with healed or almost healed leg ulcers. The group supports
      and empowers patients with self-care 'look after your legs' health promotion
      messages. The support group uses a similar model to the expert patient programme
      (Department for Health, 2001). Patients in the group coined the unique name
      'patient ambassador'. Patient ambassadors, with nursing support, are used to
      promote self care and lifestyle changes to members of the group to prevent
      recurrence of leg ulceration. The aim of the research reported here was to
      evaluate teh 'Look after Your Legs'(LAYL) service and the benefit to others of
      the patient ambassador role.

PMID- 17505353
TI  - Spreading tissue viability far and wide.

PMID- 17505352
TI  - Motivational interviewing with clients with chronic leg ulceration.
AB  - On order to meet the holistic needs of the client with chronic illness, the nurse
      is required to adopt many different approaches to care. This article will explore
      one client-centred counselling approach that can be used by community
      practitioners to address behavioural change and improve concordance. The
      techniques are illustrated with an example of where motivational interviewing has
      been used to great success--in the 'Look After Your Legs' (LAYL) programme
      undertaken by West Gloucestershire primary care trust. Interventions such as
      motivational interviewing have the potential to empower clients and so enhance
      care delivery.

PMID- 17505354
TI  - Assessment and management of wound infection: the role of silver.
AB  - The appropriate selection of anti-microbial dressings has become an increasing
      challenge within clinical practice with an increasing array of dressing
      availability. A major area of growth has been in dressings containing silver.
      This article will discuss the rationale for use of silver dressings in the
      context of wound bed preparation, and offers guidance on their selection and
      appropriate use.

PMID- 17505356
TI  - Effective communication in diagnosing Parkinson's.

PMID- 17505357
TI  - Advancing staff development and progression in nursing.
AB  - Staff development in the NHS is integral to clinical governance and therefore
      important to health service providers. It is concerned with all the activities
      that advance knowledge, skills and attitudes of staff, embracing induction,
      mentorship, continuing professional development, learning beyond registration,
      performance appraisals, promotion, personal and professional development, and
      related activities. The recent contraction in nursing posts and services and
      competition for jobs means that only well-qualified staff with an impressive
      portfolio of staff development are likely to climb the career ladder. Nursing
      staff development and training needs in the NHS are huge and multifaceted.
      Healthcare providers need to invest in clear staff development strategies if they
      are to maintain their status as effective care delivery organizations in an
      increasingly competitive market-driven economy. This article examines the many
      features of staff development and highlights the benefits for both staff and
      organizations.

PMID- 17505358
TI  - Racism in nursing education: a reflective journey.
AB  - This article discusses the personal and professional journey of discovery
      experienced by a nurse lecturer as a result of engagement in a project exploring
      the impact of racism in the nursing classroom. The findings of the study
      demonstrated the existence and complexity of racism, the impact of racism on
      student learning, the limitations of lecturers in recognizing and addressing
      racism and organizational factors which perpetuate institutional racism. The
      authors describe the insight gained from the research process and how this has
      influenced the practice of the first author and how reflection and mentorship by
      the second author have challenged personal ethnocentricity, encouraged new ways
      of thinking, enhanced confidence and encouraged experiential teaching strategies.
      The article highlights the ways in which nurse lecturers might become culturally
      competent and in particular addressing issues of racism in the classroom and
      enabling learning which is applicable in practice.

PMID- 17505359
TI  - Ten steps to developing an abstract for conferences.
AB  - There is an increasing importance being placed on the dissemination of research
      and other high quality evidence. This article is the first in a series of three
      that will assist you in ensuring that your work is presented in the best light at
      the conference of your choice. In this first article we guide you through the ten
      steps you need to take to ensure that you submit the best possible abstract to
      the scientific committee. We also will guide you through the process of
      selection.

PMID- 17505360
TI  - Ten steps to successful poster presentation.
AB  - Receiving a letter confirming acceptance for you to present a poster at a
      conference can evoke mixed emotions. Joy, panic, fear and dread are among the
      many possible emotions and this is not exclusive to first time presenters.
      Developing an effective poster presentation is a skill that you can learn and can
      provide a rewarding way to present your work in a manner less intimidating than
      oral presentation (Shelledy, 2004). The key to successful poster presentation is
      meticulous, timely, well informed preparation. This article outlines ten steps to
      help guide you through the process to maximize your success.

PMID- 17505361
TI  - Ten steps to successful conference presentations.
AB  - Delivering an oral presentation at a conference can be a demanding yet
      exhilarating experience. It can create a variety of emotions such as excitement,
      joy and achievement--but for many the overriding emotions are those of anxiety,
      fear and dread. A certain amount of nervousness can enhance your performance but
      how can you avoid pre-presentation nerves developing into full-blown anxiety and
      fear. The key to successful conference presentation is meticulous preparation and
      practise. This article guides you through ten steps to help maximize your success
      and enjoyment.

PMID- 17505362
TI  - Anatomy and physiology of urinary elimination. Part 1.
AB  - Elimination of urine is an essential bodily function, but independence in this
      activity may be affected by physical and mental disability. Part 1 of this
      article discusses the anatomy and physiology of the renal and urinary tract and
      the production of urine. Urinalysis is a vital nursing assessment and the
      collection of specimens and the range of tests undertaken are outlined. Assisting
      patients to use the toilet, commode or bedpan is an essential nursing skill. The
      importance of sensitivity, empathy and moving and handling risk assessment is
      discussed, and the assessment and management of urinary tract infection and
      urinary tract stones are addressed. The importance of prevention of cross
      infection for nurses and patients is highlighted throughout the article.

PMID- 17505363
TI  - Hot pack, nursing costs and suicide: the BJN over 100 years ago.

PMID- 17505364
TI  - Consent and capacity: principles of the Mental Capacity Act 2005.
AB  - In this series we have seen that competent adult patients have the legal right to
      withhold their consent to treatment offered to them. This rule applies to all
      areas of treatment and care, even where treatment offered is for a serious or
      severe condition. It applies equally where in the extreme situation, a refusal is
      likely to result in the person's death (House of Lords, 1994; Re MB, 1997; Re JT,
      1998; Re AK, 2001). However, many people do not meet the strict criteria that
      enables them to consider themselves 'competent'. Where a person cannot be
      considered competent, another set of legal principles are effected, by the common
      law, and now by statute.

PMID- 17505365
TI  - Testing nasogastric tube positioning in the critically ill: exploring the
      evidence.
AB  - Nutritional support in the critically ill is commonly delivered via a nasogastric
      tube. Correct positioning in the stomach must first be confirmed as inadvertent
      feeding into the lungs carries a high risk of mortality. The National Patient
      Safety Agency (2005) recommends the method of pH testing nasogastric tube
      aspirates to verify tube position. This article critically analyses the research
      supporting this method, and questions its reliability in critically ill patients
      whose gastric pH may well be altered due to prophylactic stress ulcer medications
      and continuous feeding regimens. There is a lack of quality research testing this
      method in the critically ill population. The theory-practice gap is addressed,
      and preliminary research behind use of techniques such as capnography and
      capnometry is also examined.

PMID- 17505366
TI  - Caring for people with dementia in the acute setting: a study of nurses' views.
AB  - Caring for people with dementia in an acute hospital setting presents a number of
      challenges. This article reports the findings of a study which explored nurses'
      experiences of caring for older people with dementia in a unit caring for older
      people within an acute hospital. The study used a thematic approach to produce an
      interpretation of the care experience and a purposive sample of seven nurses was
      interviewed regarding the research aims. The findings revealed the structural
      inadequacies of the acute hospital as a dementia care environment and the
      resultant challenges and complexities of the care experience. Despite the
      identified challenges, nurses considered the specific needs of people with
      dementia and the environmental effects of the acute setting on their ability to
      meet identified needs.

PMID- 17505367
TI  - Innovation, safety and cost effectiveness in IV therapy.

PMID- 17505368
TI  - Recurring themes in NHS complaints.

PMID- 17505369
TI  - Helping the 'hidden poor' when the poor are helpers.

PMID- 17505370
TI  - The usability and acceptability of a needleless connector system.
AB  - Needleless connectors were introduced into clinical practice to reduce the rate
      of needlestick injuries to healthcare workers (HCWs). There have, however, been
      limited reports of user acceptability of these devices. The usability and
      acceptability of the Clearlink needleless connector (Baxter Healthcare, UK) was
      therefore completed by HCWs at University Hospital Birmingham NHS Foundation
      Trust following a 12-month clinical evaluation. Seventy percent (28/40) of HCWs
      reported that they would prefer to use Clearlink needleless connectors rather
      than conventional luers caps, 15% (6/40) would use either, and only 15% (6/40)
      preferred to use luer caps. In total, 85% of HCWs reported that Clearlink was
      acceptable to use in the clinical situation. The results demonstrate that
      comprehensive training and technical support both before and after new device
      implementation were essential to ensure a smooth transition.

PMID- 17505371
TI  - Home intravenous therapy training for carers of children and young people.
AB  - Modernization of the health service has provided patients with an element of
      choice with health care, which has enabled parents and carers to carry out
      treatments such as home intravenous therapy (HIVT). Current literature has
      highlighted the importance of educational programmes for caregivers when
      undertaking HIVT. This article provides an overview of a training package,
      developed at Nottingham City Hospital by the children's respiratory nurses. The
      package is used to assist parents and carers with HIVT for children and young
      people with respiratory conditions, in particular, cystic fibrosis. The stages of
      a training programme are discussed, including details of an audit that
      demonstrated a good response rate in relation to how useful the training pack was
      for HIVT.

PMID- 17505372
TI  - Skin antiseptics used prior to intravascular catheter insertion.
AB  - The recent epic2 publication (Pratt et al, 2007) provides evidence-based
      guidelines for the prevention of healthcare-associated infections. One of the new
      recommendations related to the prevention of central venous catheter (CVC)
      associated infection states that 2% chlorhexidine gluconate (CHG) in 70%
      isopropyl alcohol (IPA) should be used for cutaneous antisepsis prior to device
      insertion. This article reviews cutaneous antisepsis prior to intravascular
      catheter placement.

PMID- 17505373
TI  - Clinical audit documenting insertion date of peripheral intravenous cannulae.
AB  - The Royal College Of Nursing (RCN) have evidence-based guidelines with regard to
      optimal time for changing peripheral intravenous cannulae (PIC) and documentation
      post-insertion (patient and nursing notes). This clinical audit assesses the
      compliance with respect to the RCN and Eastbourne District General Hospital
      guidelines of documenting the date post-insertion of PIC, optimal time for
      changing cannulae and rates of superficial phlebitis on the surgical wards. All
      PIC, their dressings, sites and intravenous infusions were examined on all
      inpatients on the surgical wards on three random days. Staff awareness with
      regard to RCN and local guidelines for optimal time to change peripheral venous
      cannulae and documentation post-insertion was assessed. The majority of staff
      nurses correctly stated that the optimal time for changing an uncomplicated PIC
      was 72 hours, despite this 13.8% had a cannulae which had been inserted for more
      than 72 hours. Our study has found that despite medical and nursing staff being
      aware of RCN and local guidelines, there is still poor compliance with regards to
      documentation, optimal time for changing and thus increased levels of superficial
      phlebitis post insertion of PIC.

PMID- 17505374
TI  - Patient-perceived discomfort with two coated urinary catheters.
AB  - Intermittent catheterization is now the preferred method for urethral
      catheterization of the urinary bladder when an indwelling catheter is not
      required. Nevertheless, the procedure may cause discomfort or pain. This
      randomized, prospective study was done to compare patient-perceived discomfort
      between two commonly used hydrophilic, single-use catheters in women. A total of
      196 women referred to the urogynaecology section in the outpatient department
      were randomized to be catheterized with either a LoFric (n=102) or a SpeediCath
      (n=94) catheter. Both catheters are hydrophilic, low friction, single-use,
      disposable catheters. Discomfort was measured using a visual analogue scale
      (VAS). The results showed no difference in degree of patient-perceived discomfort
      between the two groups. Median score was 0.75 VAS points in both groups, which
      indicates little discomfort. Half of all the patients stated that they
      experienced no discomfort at all.

PMID- 17505375
TI  - Ten steps to getting your paper published in a professional journal.
AB  - There is an increasing expectation that nurses, whether they work in clinical
      practice management, education or research, will publish. At the same time there
      remains a mystique about the best way to go about this. This article provides a
      simple commentary suggesting ten steps to help you publish in a professional
      journal.

PMID- 17505376
TI  - Cognitive behavioural therapy group work with voice hearers. Part 2.
AB  - This is the second of two papers that present a small, randomized control trial
      of cognitive behavioural therapy (CBT) within a group setting for the treatment
      of auditory hallucinations. In the previous paper, a method was described for an
      eight-session CBT group. Assessments were undertaken measuring control, power,
      frequency, and symptoms of distress and anxiety on commencement and on completion
      of the group. This second paper details the experience of the group and reports
      on the outcomes of the assessment measures. The study concludes that group CBT
      was helpful in the treatment of auditory hallucinations.

PMID- 17505377
TI  - Tasks and routines in 21st century nursing: student nurses' perceptions.
AB  - The aim of this study was to explore final year nursing students' views about
      their clinical experiences. This was the second of three studies using a grounded
      theory approach overall with theoretical sampling of final year student nurses
      being chosen as a result of the initial study's findings. The sample was of a
      volunteer nature. The data collection tool was an open-ended questionnaire, with
      themes arising from the first study helping to form the questions. It was
      anticipated that more clinically experienced students would confirm, refute and
      perhaps provide "new" information about the reality of clinical nursing when
      compared with the sample of neophyte nurses from the first study. Data were
      analysed through initial coding of responses and then compared and contrasted to
      the data of study one. Findings included categories of views about the nurses'
      roles and tasks, clinical priorities of qualified nurses, holistic care, and care
      plans. The conclusion suggest that despite nursing theory proclaiming the advent
      of "new" nursing with hallmarks of holistic care and movement away from tasks and
      routines, the student nurses did not find this to be the case. Indeed, tasks and
      routines are what seemed to structure the work of nurses, with little evidence of
      holistic, patient-centred care occurring clinically.

PMID- 17505378
TI  - Clinical skills: bed making and patient positioning.
AB  - Providing a clean, comfortable bed and positioning a patient in the optimum
      posture for prevention of complications and to enable maximum independence are
      fundamental nursing skills. Bed-making is a daily routine that requires practical
      and technical skills. Selecting the correct posture for a patient in bed or in a
      chair is essential for physiological functioning and recovery. In this article
      bed-making is described, as are positioning and re-positioning in relation to
      patients in bed, armchairs and wheelchairs. Infection control and moving and
      handling issues are also considered.

PMID- 17505379
TI  - Clinical skills: cardiac rhythm recognition and monitoring.
AB  - With technological advances, changes in provision of healthcare services and
      increasing pressure on critical care services, ward patients' severity of illness
      is ever increasing. As such, nurses need to develop their skills and knowledge to
      care for their client group. Competency in cardiac rhythm monitoring is
      beneficial to identify changes in cardiac status, assess response to treatment,
      diagnosis and post-surgical monitoring. This paper describes the basic anatomy
      and physiology of the heart and its conduction system, and explains a simple and
      easy to remember process of analysing cardiac rhythms (Resuscitation Council UK,
      2000) that can be used in first-line assessment to assist healthcare
      practitioners in providing care to their patients.

PMID- 17505381
TI  - Consent: the issue of rights and responsibilities for the health worker.
AB  - The next three articles discuss elements of an important part of health
      provision. Deciding who has control over health choices is controversial, and
      many health providers are confused as to the issues. The confusion would appear
      to arise in two main areas. First, definitions as to who can and cannot make
      decisions appear to some to be muddled. Second, specific new legislation that
      applies principles of consent to certain groups of healthcare users, would seem
      to be poorly understood at present. The three articles will be presented as
      follows: discussion on the legal definitions and principles of consent;
      discussion of issues surrounding the capacity of families to give or refuse
      consent to organ transplantation; discussion on the freedoms and responsibilities
      of people who are affected by the new incapacity bill.

PMID- 17505380
TI  - Nurses' views on ease of patient care in postoperative pain management.
AB  - The fentanyl HCl iontophoretic transdermal system (ITS) is a compact, needle
      free, pre-programmed patient-controlled analgesic system that was developed to
      address limitations to existing therapies for postoperative pain management. A
      randomized, controlled trial was conducted in 11 European countries to evaluate
      the efficacy and safety of postoperative pain control using fentanyl ITS compared
      with a standard regimen of morphine provided by an intravenous patient-controlled
      analgesia (IV PCA) pump. This article summarizes results from Nurse Ease-of-Care
      Questionnaires which were completed to assess the convenience and ease of use of
      each pain management modality from the perspective of the nurse. Nurses' ratings
      of patient-care tasks associated with each pain management system were
      significantly more favourable for fentanyl ITS than for morphine IV PCA. These
      findings suggest that nurses consider fentanyl ITS to be easier to use than
      morphine IV PCA.

PMID- 17505382
TI  - The isolation hospital in the training of nurses: subject of the BJN over 100
      years ago.

PMID- 17505383
TI  - Tighter controls of student mentors may be problematic.

PMID- 17505385
TI  - Needlestick injuries: is it time for a new approach?

PMID- 17505386
TI  - Pathophysiology and management of hepatic encephalopathy.
AB  - Hepatic encephalopathy is a common complication of liver cirrhosis occurring in
      up to 80% of patients and is characterized by neuropsychiatric complications
      ranging from slight altered mental status to coma. While the underlying
      mechanisms remain poorly understood with several proposed hypothesized theories,
      the mainstays of treatments are aimed at identifying and treating the
      precipitating causes or reducing intestinal ammonia production. Despite the
      increasing incidence of liver disease and liver cirrhosis within the UK, there
      have been few major advances in treatments of hepatic encephalopathy over the
      last decade. This article provides an overview of the pathogenesis, and medical
      and surgical management of this major clinical problem.

PMID- 17505387
TI  - Role of the nurse in managing patients with hepatic cerebral oedema.
AB  - Acute liver failure occurs abruptly often without pre-existing liver disease
      being present. Management comprises support of the patient and treatment of
      symptoms until recovery or transplantation can occur. Cerebral oedema is one of
      the recognized complications of acute liver failure with a mortality rate of 30
      50% when it occurs. Effective supportive nursing management includes use of
      sedative agents, positioning and thermoregulation if the patient is to recover or
      be optimized for transplantation.

PMID- 17505388
TI  - Comparative study on the effect of enteral feeding on blood glucose.
AB  - Stress hyperglycaemia is common in intensive care patients. There is recent
      evidence to suggest that maintaining the blood glucose of a patient in intensive
      care between 4 mmol/litre and 6.1 mmol/litre reduces morbidity and mortality. The
      aim of this comparative study was to determine if blood glucose control improves
      with abolishing feeding breaks and introducing continuous enteral feeding. Twenty
      ventilated patients admitted to a combined medical and surgical intensive care
      unit were sampled. Ten patients received standard care (enteral feeding for 18
      hours with an 8-hour break). The interventional group received continuous enteral
      feeding over the 24 hours. Analysis of the data revealed that continuous enteral
      feeding reduced blood glucose levels significantly, improved blood glucose
      control and reduced insulin requirements. Research should continue to determine
      if the results of this study could be replicated within a larger group of
      intensive care patients.

PMID- 17505389
TI  - Clinical skills: bowel elimination and management of complications.
AB  - Bowel elimination is a basic bodily function that most people carry out in
      private and are often embarrassed to discuss publicly. Nurses will encounter
      patients with bowel elimination issues in all areas of care. Knowledge and
      understanding of both normal function and the problems that can occur with that
      process will enable nurses to support and care for patients with bowel
      elimination problems. This article discusses the normal anatomy and physiology of
      elimination, problems, such as faecal incontinence, diarrhoea and constipation,
      and the nurse's role in their management. The importance of empathy,
      understanding, knowledge and consent is highlighted.

PMID- 17505390
TI  - Clinical skills: bed bathing and personal hygiene needs of patients.
AB  - The maintenance of personal hygiene is essential for a patient's health and well
      being. Nurses play a key role in ensuring that the individual hygiene needs of
      patients are met. In this article the process of bed-bathing a patient is
      described.

PMID- 17505391
TI  - Training nurses: subject of the BJN over 100 years ago.

PMID- 17505392
TI  - Autonomy and care: respecting the wishes of the deceased patient.
AB  - In previous articles it has been established that a duty of care is owed to all
      those for whom we care, a duty not to cause harm, to continuously aim to provide
      the best possible care and treatment, to act at all times in the best interests
      of those for whom we care. This includes respecting the autonomous choices made
      by the person regarding the treatment of their body. Autonomy is the capacity to
      think, decide and act on the basis of such thought and decision, freely and
      independently (Gillon, 1986), in other words, deliberated self-rule.

PMID- 17505393
TI  - Ten steps to convert your assignment into a journal article.
AB  - Nurses spend a great deal of time and effort in constructing a variety of
      assignments and dissertations as part of courses, both at undergraduate and
      postgraduate levels. It is not uncommon to read comments from lecturers such as
      'this requires only minimal work to be published'. It might be assumed that many
      assignments and dissertations would therefore go on to appear in print; however
      it is questionable just how many of them ever do materialize in journals. The
      reality is that this transition can be a challenging process. This is highlighted
      when a search of the literature for use in preparation for this article the
      authors discovered a dearth of advice to help potential authors make the
      transition from good quality assignment to published article. With this in mind
      we will try to guide you through a process that will assist you in converting
      your academic work into an article fit for publication.

PMID- 17505394
TI  - A qualitative study to determine the restratification of nursing.
AB  - The theory of occupational closure is a neglected area in the field of nursing.
      This article attempts to determine its relevance to nursing within the current
      political and economic climate where skills shortages within the field of
      medicine and the introduction of the European Working Time Directive in Britain,
      has presented new opportunities for nursing on several fronts. The study
      attempted to identify the impact of this policy upon the working relationships of
      doctors and nurses. It also attempted to determine how doctors and nurses
      classify the work of nursing in current context and the reasons for so doing. A
      series of semi-structured interviews were conducted with a group of doctors and
      nurses working in a large teaching hospital in the English Midlands. The study
      showed that a restratification of nursing has occurred whereby a three-tier
      classification system has emerged within the hierarchy of nursing. The findings
      have opened up a debate concerning issues of power, territorialism and new
      directions for the future of nursing.

PMID- 17505395
TI  - Don't use the term 'health promotion' to promote health.

PMID- 17505396
TI  - Efficacy of commercial dressings in managing malodorous wounds.
AB  - This paper investigates a novel in vitro method of ascertaining quantitative
      comparative data on a selection of commercial available odour absorbent wound
      dressing. The aim of this study is to determine and evaluate quantitative
      desirable data on the efficiency of odour absorbency along with other comparable
      physical characteristics of commercial odour absorbent dressings. This study is a
      part of an ongoing research programme into the design and development of novel
      odour absorbent dressings for managing malodorous wounds. The study also includes
      the development of a controlled in vitro test method that simulates a more
      realistic situation. A selection of commercially available activated charcoal
      dressings were analysed and tested, and comparative evaluation was carried out
      and discussed.

PMID- 17505397
TI  - Cellulitis and treatment: a qualitative study of experiences.
AB  - Although cellulitis is usually a relatively mild condition, it is potentially
      life threatening, often necessitating emergency treatment in either the acute or
      community care settings. The treatment of cellulitis with antibiotics is well
      established, with effectiveness generally measured against purely biochemical and
      clinical outcomes (Cox, 2002). Although important, these outcomes are centred
      purely on the disease process from the medical perspective and little is known
      about patients' experiences of cellulitis. This qualitative study explores
      patients' view on the management of community-acquired cellulitis in the
      secondary healthcare setting. Data were collected through semi-structured groups
      and individual telephone interviews. Participants were selected through purposive
      sampling and the Framework Analysis Technique was used to analyse the data. Three
      superordinate themes emerged: initial presentation/motivation for seeking help;
      confidence and satisfaction; anxiety and dissatisfaction. Severe pain was almost
      universally a cause of distress and flu-like symptoms delayed recognition. Health
      information and communication was generally poor. Participants largely welcomed a
      move from inpatient to day-patient or outpatient care provided there was adequate
      information and support. To meet the diverse needs of cellulitis patients,
      services must be more flexible and tailored to the needs of the individual.
      Patients are often not told what they can do to prevent recurrence.

PMID- 17505398
TI  - Education and training in tissue viability is readily available to all.

PMID- 17505399
TI  - Use of sterile maggots in an unusual trauma injury.
AB  - Sterile larvae of the common green bottle, Lucilia sericata, have been shown to
      be a highly cost-effective alternative to conventional treatments for the
      debridement and cleansing of all types of chronic wounds. (Thomas, 2006). One or
      two treatment cycles each lasting approximately 3 days are often sufficient to
      achieve complete debridement of such wounds, provided sufficient numbers of
      maggots are applied on each application. Maggots are less commonly used in
      traumatic injuries, although in these wounds their remarkable wound cleansing
      properties could be of considerable value.

PMID- 17505400
TI  - Optimizing wound care with a new lipido-colloid dressing (Urgotul Duo).
AB  - This non-comparative, multicentre clinical trial includes 43 patients whose acute
      or chronic wounds were treated with a new lipido-colloid dressing, Urgotul Duo,
      for at most 4 weeks, or until healing first occurred. The efficacy, tolerance and
      acceptability results obtained from this 'ready-for-use' dressing were similar to
      those reported for the Urgotul dressing in numerous previous clinical trials, and
      for all the different types of acute and chronic wounds. This well-tolerated new
      dressing greatly facilitates care operations in terms of execution (reduced use
      of supplementary gauzes for the secondary dressing) and duration (shorter nursing
      time), while improving patient comfort. This dressing is indicated for the local
      treatment of moderate exudative acute and chronic wounds in the granulation and
      epidermization phases.

PMID- 17505402
TI  - Bridging the gap: can a link nurse initiative influence palliative care in an
      acute hospital?
AB  - With 90% of people needing some inpatient hospital care in the final year of
      life, it is evident that the provision and awareness of palliative care, and
      education surrounding this, are widely needed. This study aims to evaluate a
      palliative care link nurse initiative (PCLN) in an NHS acute hospital,
      identifying key factors affecting link nurses' ability to influence palliative
      care practice. This qualitative study used semi-structured interviews and a focus
      group to show the anticipated and actual influence of link nurses on practice.
      Findings suggest that link nurses had increased knowledge and skills in
      palliative care due to education provided. Link nurses were seen to have an
      influence on the presence and quality of palliative care practice in hospital
      wards. Factors that could help link nurses to have greater influence are
      reported, as are difficulties in providing care and accessing training.

PMID- 17505403
TI  - Knowledge, attitudes and practices of nursing personnel regarding advance
      directives.
AB  - The aim of the study was to describe the knowledge, attitudes and practices of
      nursing personnel working in acute care settings regarding advance directives
      (ADs). The study was descriptive using a 40-item, newly developed tool (Update on
      Advance Directives questionnaire) distributed to 108 nursing personnel (mostly
      registered nurses) who were willing to complete the questionnaire. The findings
      were that nursing personnel reflected a lack of knowledge concerning federal and
      state laws and general information about ADs. Nursing personnel had very low
      rates of AD completion but most felt ADs were valuable for the patient. We
      concluded that nurses need more resources, e.g. knowledge, administrative and
      physician support, and communication tools to facilitate advance planning for end
      of-life care for patients. The role of the health care provider, be it the nurse,
      physician or other, needs to be clarified regarding the most practical setting
      for AD formulation.

PMID- 17505404
TI  - Spirituality in palliative care: what language do we need? Learning from pastoral
      care.
AB  - This article is a sequel to 'Spirituality in palliative care: what language do we
      need?' (Byrne, 2002). It looks at the language of pastoral care, its place in
      palliative settings and how it is regarded by patients and carers. Spirituality
      and spiritual need is multifaceted, and the various beliefs regarding the concept
      of spirituality and the spiritual needs of terminally ill patients are appraised,
      and the methods of spiritual assessment reviewed. The role of the chaplain in
      spiritual care is also assessed, and an ability to move beyond the boundaries of
      their own denominational position addressed. Several components of the language
      of pastoral care are identified.

PMID- 17505405
TI  - Palliative care provision in Huntington's disease.
AB  - There is currently much interest regarding the needs of people affected by non
      malignant disease and whether or not these are being met by palliative care
      services. The evidence available appears to support the conclusion that while
      there is a general inequality of access, some individuals with non-malignant
      conditions such as cardiac disease and motor neurone disease are able to access
      palliative care services more readily than others. Huntington's disease (HD) is a
      devastating neurological condition of long duration and as such may have a
      lengthy palliative phase. Consequently, a diagnosis of HD will have a major
      impact on the quality of life of the affected individual and their family. For
      carers, an understanding of this challenging disease and its prognosis is
      essential for the provision of appropriate and effective care. This article
      reviews the links between HD and palliative care and discusses some of the
      challenges facing patients, families and health care professionals in adopting a
      palliative approach in the management of the disease.

PMID- 17505406
TI  - The challenge of providing palliative care to terminally ill prison inmates in
      the UK.
AB  - Terminally ill prison inmates have a right to all aspects of health care
      including palliative care provision. However, there are numerous difficulties in
      providing palliative care to high-security prisoners in the UK. Local community
      hospices may be reluctant to admit terminally ill prisoners and therefore
      initiatives must be established to provide appropriate palliative care within the
      prison itself. Dying prisoners need companionship and to be shown respect and
      compassion to avoid feelings of loneliness and hopelessness. Inmate volunteers
      can provide an invaluable source of support and friendship for the terminally ill
      prisoner, helping to improve quality of life.

PMID- 17505407
TI  - A palliative approach to the management of malodour from malignant fungating
      tumours.
AB  - The aim of this case study is to explore the role of palliative care and the
      importance of a multidisciplinary team approach for the management of malodour
      from malignant fungating tumours. Nurses in my practice area in the UK rarely see
      them, find them particularly difficult to manage and the experience is often
      personally distressing. The disturbing nature of these tumours inflicts so much
      suffering on the patient and those around them that the concept of palliative
      care is often severely challenged and can prove to be difficult for nurses to
      achieve. Palliative care aims to provide a holistic team approach in addressing
      the complex individual needs of these patients and their families.

PMID- 17505408
TI  - Drugs for cardiac arrhythmias.

PMID- 17505409
TI  - A new sunscreen agent.

PMID- 17505410
TI  - Insulin-like growth factor-1 for severe growth failure.

PMID- 17505411
TI  - Historical background and current problems of OPCAB in Japan and some candid
      advice.

PMID- 17505412
TI  - The present status of postoperative adjuvant chemotherapy for completely resected
      non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung
      cancers, with patients having a poor prognosis. Approximately one third of NSCLC
      patients present with early-stage disease in which potentially curative resection
      and multi-modality therapy. Although adjuvant chemotherapy is the standard
      practice for patients with stages I-III breast and colorectal cancer, the
      therapeutic efficacy of adjuvant chemotherapy, following complete surgical
      resection of early stage NSCLC, has not been fully established. Several
      prospective randomized trials for patients with early stage NSCLC (stages I-IIIA)
      have confirmed a survival benefit with cisplatin-based adjuvant chemotherapy, as
      demonstrated in the 1995 meta-analysis performed by the NSCLC Collaborative
      Group. Studies from Japan have reported that adjuvant therapy with uracil-tegaful
      (UFT) afforded an improvement of 4% in the 5-year survival rate and a relative
      risk reduction of 26% in mortality at 5 years among patients with T1-2N0 (stage
      I) disease. In particular, the Japan Lung Cancer Research Group has demonstrated
      an improvement in the 5-year survival rate of 11%, favoring chemotherapy with UFT
      in the subset of patients with T2N0 (stage IB) disease. Two published meta
      analyses based on abstracts have estimated a relative risk reduction in mortality
      of 11-13% at 5 years. The Lung Adjuvant Cisplatin Evaluation (LACE), which was
      based on a pooled analysis of five randomized trials, has demonstrated that
      cisplatin-based adjuvant chemotherapy improved survival in patients with
      completely resected NSCLC. This benefit depended on stage, being greatest in
      patients with stage II or IIIA disease. This analysis has suggested that platinum
      based adjuvant chemotherapy may have no benefit for patients with stage IA and
      only a marginal benefit for patients with stage IB. Thus, the information
      available at the current time supports the administration of adjuvant
      chemotherapy for patients who have undergone complete resection of stages IB-IIIA
      NSCLC. Further research is needed to define the role of adjuvant platinum-based
      chemotherapy and its use, in conjunction with chest radiotherapy as the treatment
      for patients with resected stages IB and IIIA NSCLC.

PMID- 17505413
TI  - Leiomyoma of esophagus.
AB  - Leiomyomas are rare benign esophageal neoplasms with an indolent clinical course.
      Symptoms mimic that of esophageal cancer. Esophagoscopy and endoscopic
      ultrasonography are the main diagnostic methods. Symptomatic and large leiomyomas
      should be treated surgically while small, asymptomatic lesions may be managed by
      regular follow up and repeated endoscopies.

PMID- 17505414
TI  - Met-RANTES ameliorates fibrous airway obliteration and decreases ERK expression
      in a murine model of bronchiolitis obliterans.
AB  - OBJECTIVES: Bronchiolitis obliterans (BO) is the main cause of late mortality
      among long-term survivors of lung transplantation. Chemokine-chemokine receptor
      (CCR) interaction and subsequent recruitment of infiltrating cells to the graft
      are early events in the development of chronic rejection of transplanted lungs.
      The present study investigated whether blockade of chemokine receptors CCR1 and
      CCR5 with Met-regulated-on-activation, normal T cells expressed and secreted
      (RANTES), an amino-terminal modified derivative of RANTES/CCL5, affects the
      development of BO in murine model and we sought to determine the expression of
      RANTES/CCL5 and their relationship with extracellular signal-regulated kinase
      (ERK). MATERIALS AND METHODS: BALB/c mouse tracheas were heterotopically
      transplanted into C57Black6 recipients and treated for 21 days with either Met
      RANTES at 20 microg/day or vehicle. Animals were killed at 21 days after
      transplantation for histologic examination of ERK expression. RESULTS:
      RANTES/CCL5 was highly expressed in allografts compare to isografts. Met-RANTES
      treatment ameliorated fibrous airway obliteration in a mouse model of BO and
      decreased ERK expression. CONCLUSION: Blockade of chemokine receptors by Met
      RANTES ameliorated airway obliteration and decreased ERK expression. These
      findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in
      the development of chronic rejection and ERK may be a new molecular target for
      chronic rejection.

PMID- 17505415
TI  - Epidermal growth factor receptor gene mutations in early pulmonary
      adenocarcinomas.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations are frequently
      found in pulmonary adenocarcinomas. MATERIALS AND METHODS: Various lung cancers
      (n=30) including 8 small adenocarcinomas were examined for EGFR gene mutations in
      three exons. RESULTS: Mutations were detected in 32% of adenocarcinomas. Exon 19
      mutations were detected in 5 tumors, often advanced stages: 1 in Noguchi's
      pathologic type C, 2 in type D, and 2 in type F. Exon 21 mutations were detected
      in 3 tumors, all small adenocarcinomas in type C, at pathologic stage IA.
      CONCLUSION: We suspect that exon 21 mutations are early events in small
      bronchioloalveolar carcinomas, while exon 19 mutations are later events occurring
      in adenocarcinomas of various types.

PMID- 17505416
TI  - Antegrade selective cerebral perfusion combined with deep hypothermic circulatory
      arrest on cerebral circulation: comparison between pulsatile and nonpulsatile
      blood flows.
AB  - PURPOSE: In aortic arch surgeries, antegrade selective cerebral perfusion (SCP)
      combined with deep hypothermic circulatory arrest (DHCA) has been recently widely
      used in institutions as one of the most reliable methods for cerebral protection.
      However, some studies reported a 3.7-9.3% incidence of postoperative cerebral
      complications. To perform antegrade SCP more safely, we sought to examine the
      impact of pulsatile flow perfusion during DHCA on cerebral tissue metabolism,
      focusing on physiological effects of pulsatile flow perfusion. MATERIALS AND
      METHODS: Sixteen pigs were divided into 2 groups. In each group, antegrade SCP
      combined with DHCA was conducted. During circulatory arrest, for SCP, a pulsatile
      flow (group P) and a nonpulsatile flow (group N) were used. We compared results
      between group P and group N. Jugular venous oxygen saturation (SjO(2)) and
      cerebral tissue oxygen partial pressure (PtO(2)) were measured at baseline, and
      continuously throughout the extracorporeal circulation. Hematocrit (Ht), and
      concentrations of S-100 protein and CK-BB in blood and the cerebrospinal fluid
      (CSF) were measured at baseline (before the beginning of extracorporeal
      circulation), following SCP, and after rewarming. Following rewarming, each brain
      under perfused fixation was removed, and histopathological examinations were
      conducted using Kluver-Barrera and Tunnel staining methods, electron micrograph.
      RESULTS: SjO(2) was found to be within normal ranges until after SCP, but
      decreased with rewarming in both groups. In Group N, changes in SjO(2) were
      significant, with a decrease to < or =50%. In Group N, concentrations of S-100
      protein and CK-BB in CSF after SCP and after rewarming were significantly higher
      than those in Group P. The time needed for rewarming to 36 degrees C in Group P
      was shorter than that in Group N. CONCLUSION: Our results suggest that the
      pulsatile flow circulation method shows cerebral protection effects with
      increasing blood flow in small cerebral tissues. In addition, it is effective for
      improving the imbalance between oxygen supply and demand, especially in the
      process of rewarming from hypothermic conditions. This method seems to be useful
      as an adjunct in hypothermic circulatory arrest procedures.

PMID- 17505417
TI  - A new storage solution for porcine aortic valves.
AB  - The aim of this study was to assess the calcification tendency of two biovalves
      manufactured by different fixation techniques and compare their biocompatibility
      when implanted subcutaneously in rats. Two biological valve types (Intact) and
      Mosaic, stored in either glutaraldehyde or in a solution recently developed in
      our department, were investigated ultrastructurally and their calcium content was
      measured following 12 weeks subcutaneous implantation in rats. All valves tested
      in this study showed a considerable loss of the endothelial cover, as judged by
      scanning electron microscopy. Independent of fixation conditions, the
      bioprostheses demonstrated a partial destruction of collagen fibers and a
      rearrangement of the extracellular matrix. The calcium content of Intact valves
      was significantly higher than that of Mosaic valves (66+/-2.6 versus 3.6+/-0.6
      mg/g dry tissue, p<0.0001). Low calcium content of the bioprostheses is
      considered to result from effective anti-calcification treatment. Ultrastructural
      changes of prosthetic tissue seem to promote degenerative calcification. The
      valves stored in the new storage solution exhibited a calcium content which was
      reduced by approximately 50% compared to those stored in glutaraldehyde. The
      percentage of reduction in calcification of the valves stored in our newly
      developed solution is independent of the fixation conditions (p=0.886). The
      advantage of the new storage solution is based on the fact that rinsing is
      unnecessary before implantation and, most importantly, a clear reduction in the
      calcification tendency is achieved.

PMID- 17505418
TI  - Carcinoma arising from an epiphrenic diverticulum: a frequently misdiagnosed
      disease.
AB  - Epiphrenic diverticulum is rare, comprising of about 10% of all esophageal
      diverticula. Carcinoma arising within such a diverticulum is even less common. We
      report on two patients with squamous cell carcinoma arising from an epiphrenic
      diverticulum. Some features of malignant change related to the epiphrenic
      diverticula were misdiagnosed or missed in our cases and other reports due to
      lack of clinical experience. It is important to exclude the possibility of
      malignancy as this is vital for surgical planning. Although the prognosis for
      patients with malignancy arising from an epiphrenic diverticulum is generally
      poor, a high index of suspicion may increase the chance of cure.

PMID- 17505419
TI  - Thymolipoma combined with hyperthyroidism discovered by neurological symptoms.
AB  - Thymolipomas are rare slow-growing mediastinal thymic neoplasms. Most cases are
      asymptomatic and are sometimes discovered as a huge mass on chest x-ray films. A
      few cases have been discovered during examinations for other diseases. We report
      the second case of thymolipoma combined with hyperthyroidism in the English
      language literature. Neurological symptoms suddenly appeared in a 45-year-old
      woman. Central nervous system disorder was suggested but no significant
      abnormalities were found on brain MR nor were there any neurological signs.
      Several months later, neurological and systemic examinations on admission
      revealed hyperthyroidism and an anterior mediastinal tumor, 9.0x5.0x3.0 cm in
      size on chest CT films. Despite treatment of hyperthyroidism by medication, her
      neurological symptoms remained. Neurologists recommended resection of the
      mediastinal tumor. Malignancy could not be ruled out because of the irregularity
      of the tumor appearance on contrast-enhanced chest CT. Furthermore, the tumor
      appeared to be attached to the ascending aorta, so cytological and/or
      pathological diagnosis by CT-guided needle biopsy before operation were
      contraindicated. Extended thymectomy was performed in May 2005. The pathological
      diagnosis was benign thymolipoma consisting of mature fatty tissue and thymic
      tissue structures with Hassall's corpuscles. Her neurological symptoms seemed
      slightly but not markedly improved. The relationship between thymolipoma and
      hyperthyroidism is still unknown.

PMID- 17505420
TI  - Ectopic cystic thymoma associated with Raynaud's phenomenon.
AB  - Mediastinal cystic tumors are well-marginated round lesions that comprise 12% to
      18% of all mediastinal masses. These lesions include a variety of diseases with
      overlapping radiologic appearances and variable prognoses. Pathological
      examinations are almost always required for differential diagnosis. We
      encountered a case of anterior mediastinal tumor discovered in the process of
      investigation of Raynaud's phenomenon. Taking into account the tumor location, a
      pericardial cyst was initially suspected. However, the tumor was surgically
      resected and histopathological examinations demonstrated thymus-like tissue in
      the cyst walls. Raynaud's phenomenon greatly improved after surgery. These
      findings suggested that cystic thymoma originated from ectopic thymic tissue and
      is accompanied by paraneoplastic syndrome.

PMID- 17505421
TI  - Ectopic thyroid cancer.
AB  - Ectopic thyroid tissue may be encountered anywhere from the foramen caecum to the
      lower neck. It is rarely seen in the mediastinum. True malignant transformation
      in ectopic thyroid tissue is extremely rare. Such a malignancy is virtually
      always diagnosed after surgical excision of the lesion at pathological
      examination. We report on an extremely rare case of true mediastinal thyroid
      cancer in a 45-year-old woman. The clinicopathologic features and diagnosis of
      the lesion, with regard to its mediastinal location are discussed.

PMID- 17505422
TI  - Successful surgical repair of an elderly patient with tetralogy of Fallot: a case
      report.
AB  - We report on a rare case of a 61-year-old female patient with tetralogy of Fallot
      who had a late radical repair. The patient had no previous surgical
      interventions, and her postoperative course was uneventful. One year after the
      repair, the patient is doing well and has no symptoms of cardiac failure.
      Surgical treatment greatly benefited our patient by improving her functional
      status and extending her life expectancy.

PMID- 17505423
TI  - Stentless aortic root bioprosthesis implantation and coronary artery bypass
      grafting in a patient with single right coronary artery.
AB  - Coronary arteries with anomalous origin from the aorta can be a risk factor
      during aortic root procedures. We report on the successful management of aortic
      root surgery in a 76-year-old man with a single coronary ostium. Preoperative
      computed tomography and angiography revealed an anomalous course of the left main
      coronary artery from the right sinus of Valsalva. A stentless aortic root
      bioprosthesis (Prima Plus) was implanted using a modified subcoronary technique.
      The origin of the left main coronary artery was approximately 2 mm beyond the
      ostium of the common trunk. Attention to the anatomic relationship of the
      anomalous coronary arteries to the aorta by clarifying the anatomy of coronary
      arteries in advance allowed us to safely perform aortic root surgery in a patient
      with an anomalous origin of the coronary arteries.

PMID- 17505424
TI  - Dysphagia due to aortic diverticulum: an adult surgical case.
AB  - A right aortic arch is an anatomic variant only occurring in approximately 0.1%
      of the population. A mirror-image right artic arch without congenital cardiac
      anomaly is fairly uncommon. We report on a rare case of dysphagia due to isolated
      aortic diverticulum in a mirror-image right aortic arch. A 72-year-old man
      presented with dysphagia which was due to posterior compression of the esophagus
      by a dilated aortic diverticulum. There was no vascular ring and we thought that
      the pathology was atherosclerotic dilatation of the diverticulum. Graft
      replacement of the diverticulum was sufficient to relieve his symptom.

PMID- 17505425
TI  - A case of unilateral leg edema due to abdominal aortic aneurysm with aortocaval
      fistula.
AB  - Aortocaval fistula (ACF) is a rare complication of abdominal aortic aneurysm
      (AAA), and its preoperative diagnosis is often difficult. A 71-year-old woman was
      admitted to our hospital due to unilateral leg edema. Abdominal computed
      tomography (CT) showed an abdominal aortic aneurysm (AAA), a common iliac aortic
      aneurysm (CIAA) and ACF was suspected. Digital subtraction angiography (DSA) was
      performed, enabling us to identify the region of ACF with AAA preoperatively. ACF
      is associated with high mortality because it is difficult to control venous
      bleeding from ACF. Detailed preoperative diagnosis of ACF can provide many
      advantages to control bleeding from ACF during an operation.

PMID- 17505426
TI  - Atherosclerotic aneurysm of the right subclavian artery: report of a case.
AB  - Subclavian artery aneurysms are uncommon. The most common causes of these
      aneurysms are atherosclerosis and traumatic pseudoaneurysm. We report on a case
      of an atherosclerotic aneurysm of the right subclavian artery. The aneurysm was
      resected with a combined supra-infraclavicular approach, and a primary end-to-end
      anastomosis was performed. The postoperative course was uneventful. In
      arteriosclerotic cases, the axillobrachial artery is frequently tortuous, and the
      proximal axillary artery can be mobilized. If possible, a direct end-to-end
      anastomosis is recommended for the aneurysm of the distal part of the subclavian
      artery.

PMID- 17505427
TI  - Successful repair using innominate vein flap, pericardial flap and thymus pedicle
      flap for tracheo-innominate artery fistula.
AB  - Tracheo-innominate artery fistula (TIF) is a rare but frequently fatal
      complication after tracheostomy. Without operation, the mortality is nearly 100%
      because of acute massive tracheal hemorrhage. Although the survival rate is
      extremely low, survival is possible only when an immediate operation is
      performed. Many surgeons have chosen ligation or resection of the innominate
      artery because repair with blood flow maintained in the innominate artery carries
      a high risk of postoperative fatal recurrent bleeding. We report on a successful
      surgical management of one case by patch closure with an innominate vein flap,
      wrapping of the innominate artery with a pericardial flap, and interposition of a
      thymus pedicle flap between the innominate artery and the trachea. Our surgical
      procedure is effective in maintaining the patency of the innominate artery
      preventing neurological deficits, and in preventing postoperative recurrent
      bleeding.

PMID- 17505428
TI  - Popliteal aneurysms.

PMID- 17505429
TI  - Endovascular treatment of asymptomatic popliteal aneurysms: 8-year concurrent
      comparison with open repair.
AB  - AIM: The aim of this prospective comparative study was to compare the results of
      8-years experience of endovascular treatment (ET) of popliteal aneurysms (PAs)
      using the Hemobahn/Viabahn endograft with those achieved with open repair (OR).
      Endpoints were primary and secondary patency rate. METHODS: The study was a
      prospective randomized clinical trial from January 1999 to December 2003 and a
      prospective comparative study from January 2004 to December 2006. Patients with
      an asymptomatic aneurismal lesion in the popliteal artery 2 cm at angio-computed
      tomography were included in the study. Indication for ET was PA (proximal and
      distal neck length >1 cm); contraindications were: 1) age <50 years; 2) poor
      distal run-off; 3) contraindication to antiplatelet, anticoagulant or
      thrombolytic therapy. RESULTS: Between January 1999 and December 2006, of a total
      of 42 patients with 48 PA, 27 were treated with OR (group A) and 21 with ET
      (group B). The primary patency rate was 100% in group A and 80.9% in group B at
      12 months and 71.4% and 88.1%, respectively, at 72 months; the secondary patency
      rate at 72 months was 88.15% and 85.9% in groups A and B, respectively. No
      statistical differences were observed at the log-rank test. During the entire
      study period, 3 (14.3%) patients in group B required conversion to open surgery
      because of endograft occlusion. CONCLUSION: Within the power limitations of this
      study, ET for asymptomatic PA in patients with suitable anatomy can be considered
      safe, with long-term results comparable with those of OR.

PMID- 17505430
TI  - Endovascular treatment of popliteal artery aneurysms: is the technique a valid
      alternative to open surgery?
AB  - AIM: Feasibility of endovascular repair of popliteal artery aneurysms has been
      established. The results of this technique and the effect of the learning curve
      on the occurrence of complications were evaluated in a prospective cohort.
      METHODS: Between June 1998 and February 2007, 73 popliteal aneurysms were treated
      by endovascular means. Primary outcome was stent-graft patency. Secondary outcome
      was a combined end-point of stent-graft related complications, including
      occlusion, migration, stent-graft fracture, and stenosis. To study the learning
      curve, the cohort of patients was divided into 2 groups (group A from 1 to 23;
      group B from 24 to 73). Cut-off point chosen was the introduction of the more
      aggressive postoperative anticoagulation protocol with clopidogrel. RESULTS:
      Eighteen (25%) stent-grafts occluded. This resulted in a reintervention in 11
      patients. Migration, fracture, and stenosis were diagnosed in 9, 3 (2 leading to
      occlusion), and 2 limbs, respectively; these 14 complications accounted for
      reinterventions in 8 additional patients. In total, 19 of the 73 limbs (26%)
      required 20 reinterventions. Overall 3-and 5-year patency rates were 77% and 70%
      for primary patency, and 86% and 76% for secondary patency, respectively. There
      were more occlusions in group A (8/23, 35%) versus group B (10/50, 20%) (P=
      0.22). With regard to the combined endpoint, there were more events in group A
      (14/23, 61%) than in group B (16/50, 32%) (P= 0.016). CONCLUSION: Results of
      endovascular repair of popliteal artery aneurysms are improving and in range with
      those of open repair.

PMID- 17505431
TI  - Surgical and endovascular treatment of atherosclerotic popliteal artery
      aneurysms.
AB  - Popliteal artery aneurysms are the most common peripheral aneurysms. Patients
      with unrecognized aneurysms may present with acute limb ischemia and considerable
      threat for limb loss due to thromboembolic complications. This article reviews
      short-term and long-term results of surgical and endovascular treatment for
      mainly elective repair of popliteal artery aneurysms. A systemic review was
      conducted of data in the English literature from 1990. The review included 1
      prospective randomized trial, 6 prospective studies, and 42 retrospective studies
      on the management of popliteal artery aneurysms. These studies contained 2 197
      patients with 2 882 popliteal artery aneurysms. Short-term results are
      acceptable, with average 1-year patency rates of 90% for surgical treatment and
      75% for endovascular treatment, and respective limb salvages rates of 95% and
      100%. Endovascular treatment lacks long-term follow-up, whereas venous surgical
      repair has an average 5-year patency rate of up to 85% (prosthetic grafts, 40
      80%). There is a need for randomized trials comparing long-term results of
      surgical versus endovascular treatment of popliteal artery aneurysms. So far,
      long-term results of elective surgical repair for popliteal artery aneurysms are
      acceptable if venous grafts are used. In any case, acute repair of popliteal
      artery aneurysms must be avoided.

PMID- 17505432
TI  - Emergency intervention for thrombosed popliteal artery aneurysm: can the limb be
      salvaged?
AB  - We present a review and our own experience of the demographic aspects of
      popliteal artery aneurysms (PAAs), their clinical presentation, the treatment
      alternatives and associated outcome. The incidence of PAA:s varies between 0,1
      1%. 95% of the patients are male. 50% are asymptomatic at the time of diagnosis.
      Annually, 5-24% of PAAs develop symptoms. The clinical presentation varies widely
      with an amputation rate of up to 78% in acute ischemic cases. The main indication
      for PAA repair is prevention of embolisation but acute revascularisation is the
      primary task in the emergency setting. Open surgery and endovascular techniques
      are described and can be combined with intraarterial thrombolysis as pre- or
      intraoperative treatment. The literature proves often inconclusive due to small
      numbers of heterogenous cases. Each case, therefore, needs to be assessed
      individually and offered the most suitable treatment.

PMID- 17505433
TI  - Can carotid ultrasound predict plaque histopathology?
AB  - AIM: European and North American studies have confirmed the benefits of carotid
      endarterectomy for patients with symptomatic carotid artery stenoses >70%.
      However, the management of asymptomatic patients and those with lesser degrees of
      stenosis is less certain. Several studies have suggested that, for these
      subgroups, the targeting of potentially unstable plaques, may help to identify
      those most at risk of cerebrovascular accidents and thus most likely to benefit
      from surgery. The aim of this study was to correlate the ultrasound features of
      carotid artery stenosis with the histopathological findings of the carotid
      endarterectomy specimens in order to identify features which will allow
      preoperative identification of clinically unstable plaques. METHODS: Sixty
      consecutive patients with symptomatic, critical carotid stenosis were
      prospectively studied. Plaques were classified preoperatively into one of five
      types based on their echogenicity and were also assessed for irregularity and
      ulceration. These findings were then compared with the histopathological findings
      of the endarterectomy specimen. RESULTS: Of 33 plaques considered on ultrasound
      to be uniformly or predominantly echolucent (unstable), 27 were found to be
      largely fatty or haemorrhagic (PPV =82%). Of 17 plaques considered to be
      predominantly echogenic (stable) on ultrasound, 11 were found to be predominantly
      fibrotic (PPV = 65%). Correlation between ultrasound irregularity or ulceration
      and histopathology was poor. CONCLUSION: In routine clinical practice, ultrasound
      can identify with reasonable accuracy, plaques that are predominantly
      haemorrhagic or fatty, and therefore potentially unstable. This may have future
      implications in selection of patients for surgery.

PMID- 17505434
TI  - Inflammatory abdominal aortic aneurysms. A 20-year experience.
AB  - AIM: The aim of the study was to report a 20-year single Institution experience,
      with the early and late outcomes of surgical treatment of inflammatory abdominal
      aortic aneurysms. METHODS: In a 20-year period, 2 275 consecutive patients
      underwent elective surgical repair for non-rupture abdominal aortic aneurysm.
      Fifty-two patients (2.3%) were classified as inflammatory abdominal aortic
      aneurysms. Early and late outcomes were analyzed. RESULTS: One patient died in
      the perioperative period, giving a mortality rate of 1.92%. One patient died from
      a pseudoaneurysm rupture 7 months after operation. Three patients developed an
      aortic pseudoaneurysm in the follow-up period (mean 12.1 years, range 1-20 years)
      and underwent a redo operation. CONCLUSION: Overall surgical outcome of these
      patients, in terms of short-term and long-term is good. A high rate of
      pseudoaneurysm formation was observed.

PMID- 17505435
TI  - Clinical outcome after re-occlusion of initially successful remote endarterectomy
      of the superficial femoral artery.
AB  - AIM: The clinical consequences of re-occlusion after initially successful
      arterial revascularization procedures might be as important as patency when it
      comes to procedure selection. This study evaluates the clinical consequences of
      re-occlusion after initially successful remote superficial femoral artery
      endarterectomy (RSFAE), in particular the recurrence and severity of symptoms and
      the need for re-intervention or amputation. METHODS: A total of 239 successful
      RSFAEs were performed with a mean endarterectomized segment of 30 cm (10 to 45
      cm) between March 1994 and December 2003 in 214 patients (144 males, 163
      procedures) with a median age of 63 years (39 to 89 years). Indications for
      operation were Rutherford category 3 in 174 procedures (73%), Rutherford category
      4 in 27 procedures (11%), and Rutherford category 5 in 38 procedures (16%). The
      incidence and time interval of re-occlusion with the presenting symptoms were
      recorded as well as the therapeutic consequences. RESULTS: A total of 79 (33%) re
      occlusions occurred (40 males, 41 procedures; 34 females, 38 procedures). Eighty
      percent of patients still had improved or unchanged symptoms following re
      occlusion compared to the initial indication for operation, 18% had become worse
      and 2% were unknown. The mean time between RSFAE and re-occlusion was 17 months
      (1 day to 88 months). A total of 36 re-interventions were performed: 7
      percutaneous recanalisations (one followed by thrombolysis), 5 percutaneous
      thrombolyses, 1 thrombectomy, 21 venous and 2 prosthetic femoropopliteal
      bypasses. A further three venous bypasses were planned. Five (14%) of these re
      interventions were acute with an overall median time interval between re
      occlusion and re-intervention of 41 days (0 to 68 months). Two below-knee
      amputations were performed: one the same day of re-occlusion, 44 months after
      RSFAE and one 11 days after re-occlusion, 30 days after RSFAE. CONCLUSION: The
      clinical consequences of re-occlusion after remote endarterectomy for long
      occlusive disease of the superfricial femoral artery, from a mixed patient
      population with 27% ischemic rest pain and gangrene, were mild with 31 elective
      and only five acute re-interventions and two below-knee amputations.

PMID- 17505436
TI  - The endovascular management of open aortic surgery complications with emergency
      stent-graft repair in high-risk patients.
AB  - The aim of the study was to demonstrate the utility of endovascular stent-graft
      repair for emergency management of aorto-iliac surgery complications. Between
      1997 and 2004, in our institute, 201 patients underwent transluminal endovascular
      graft placement. In 3 patients (1.4%), previously submitted to conventional
      aortic surgery, endovascular treatment was carried out due to the occurrence of
      late complications: 1 secondary aortocaval fistula, 1 impending rupture of aortic
      pseudoaneurysm and 1 secondary aorto-enteric fistula. All candidates were high
      surgical risk patients (ASA III-IV) suitable for endoprosthesis positioning by
      endovascular stent-graft implantation presenting with severe worsening conditions
      in an emergency situation. The patients were treated under local anesthesia and
      mild sedation. After treatment there was complete resolution of the clinical
      presentation and an improvement of general conditions in all 3 patients. In the
      1(st) patient legs edema disappeared and in the 2(nd) patient mesogastric pain is
      absent, respectively at 30 and 8 months. The 3(rd) patient, with secondary aorto
      enteric fistula, was submitted 2 months later to aortic graft removal and axillo
      bifemoral bypass because of infection development. For the treatment of abdominal
      aortic surgery complications in high risk patients, particularly in emergency
      situations, endovascular approach is a feasible and safe alternative to
      conventional open repair. Further evaluation of this technique and longer follow
      up will determine its exact role in the management of these life-threatening
      complications.

PMID- 17505437
TI  - Evaluation of the topical hemostatic efficacy and safety of TISSEEL VH S/D fibrin
      sealant compared with currently licensed TISSEEL VH in patients undergoing
      cardiac surgery: a phase 3, randomized, double-blind clinical study.
AB  - AIM: TISSEEL VH is the only commercially available fibrin sealant indicated as an
      adjunct to conventional methods of hemostasis during cardiac surgery. A next
      generation fibrin sealant (TISSEEL VH S/D) has been developed in frozen, ready-to
      use form with an added virus inactivation step (solvent/detergent [S/D]
      treatment) to provide added safety and convenience to the currently licensed
      product. This study was performed to compare efficacy and safety of the two
      products. METHODS: Phase 3, prospective, randomized, double-blind, multicenter
      study to compare TISSEEL VH S/D to TISSEEL VH during cardiac surgery. The primary
      efficacy endpoint was the proportion of patients who achieved hemostasis at the
      primary treatment site within 5 min, and maintained hemostasis until surgical
      closure. RESULTS: The proportion of patients who achieved hemostasis at the
      primary treatment site within 5 min, and maintained hemostasis until surgical
      closure was 88.2% for TISSEEL VH S/D and 89.6% for TISSEEL VH in the intent-to
      treat population. The difference in proportions, TISSEEL VH S/D minus TISSEEL VH,
      was 1.4% with a standard error of 3.70%. The lower 97.5% confidence bound of this
      difference was 8.6%, which is above the predefined noninferiority margin of 15%.
      Therefore, TISSEEL VH S/D is at least as efficacious as TISSEEL VH. The safety
      profile of TISSEEL VH S/D was very similar to that of currently licensed TISSEEL
      VH as assessed by the safety endpoints. CONCLUSION: TISSEEL VH S/D is safe and
      effective for use as an adjunct to hemostasis in patients undergoing cardiac
      surgery.

PMID- 17505438
TI  - Robotically enhanced minimally invasive direct coronary artery bypass surgery: a
      winning strategy?
AB  - AIM: Minimally invasive direct coronary artery bypass (MIDCAB) through a small
      anterolateral thoracotomy on the beating heart can be considered as the better
      approach for treating isolated lesions on the left anterior descending (LAD)
      artery. This original MIDCAB procedure, however, involves a larger and often
      painful thoracotomy due to rib spreading. We describe our experience with
      robotically enhanced harvesting of one or both internal mammary arteries (IMAs),
      and with anastomosis performed under direct vision on a beating heart through a
      very small thoracotomy without rib retraction. METHODS: Between February 2001 and
      January 2006, 146 consecutive patients underwent robotically enhanced MIDCAB
      surgery. Perioperative and early follow-up data were analyzed. RESULTS: In all,
      144 left and 13 right IMAs were harvested. The mean extubation time was 11.3 h,
      the mean intensive care (ICU) stay was 30.3 h, the mean hospital stay 8 days.
      There were no in-hospital deaths, postoperative myocardial infarctions or renal
      failures. Systematic control angiograms performed in the first 64 patients showed
      a 96.3% patency rate of the investigated anastomoses. CONCLUSION: Robotically
      assisted takedown of the IMA and direct off-pump anastomosis through a small
      anterolateral thoracotomy with no rib retraction appears to be safe, with minimal
      morbidity, little blood loss, and a reasonable ventilation time, ICU and hospital
      stay. It is recommended as the preferred method of revascularization for a
      growing number of indications and certainly an acceptable alternative to
      percutaneous transluminal coronary angioplasty.

PMID- 17505439
TI  - Aortocoronary bypass grafting in high-risk patients over 75 years. Propensity
      score analysis of on versus off-pump, early and midterm results.
AB  - AIM: Bypass surgery in high risk patients over the age of 75 results in increased
      mortality and morbidity, which may be also related to the cardiopulmonary bypass
      system. METHODS: Using the propensity score analysis, we have selected two
      homogeneous groups of high-risk elderly patients undergoing coronary surgery: 41
      patients operated with cardiopulmonary bypass- coronary artery bypass graft (CPB
      CABG), and 78 patients operated without cardiopulmonary bypass (off-pump coronary
      artery bypass graft, OPCABG). All preoperative and operative variables were
      similar and outcomes were compared. RESULTS: Perioperative mortality was higher
      in the patient group operated with CPB (12.2%) as compared to patients operated
      without CPB (1.3%, P = 0.01). Perioperative complications were more frequent in
      the CPB-CABG group. Logistic regression analysis showed that avoiding CPB was an
      independent protective factor for mortality and morbidity. Midterm survival,
      freedom from angina, freedom from reintervention, and Canadian Cardiovascular
      Society (CSS) class were comparable between the 2 groups. CONCLUSION: OPCABG is
      safe in the high risk elderly population and significantly reduces postoperative
      mortality and morbidity. There are no differences in midterm results between the
      2 groups of patients in our study.

PMID- 17505440
TI  - Impact of complications on outcomes following aortic and mitral valve
      replacements in the United States.
AB  - AIM: Heart valve replacement surgeries account for 20% of all cardiac procedures.
      In-hospital mortality rates are approximately 6% for aortic valve replacements
      and 10% for mitral valve replacements. The objectives of the study are to provide
      nationally representative estimates of complications following aortic and mitral
      valve replacements and to quantify the impact of different types of complications
      on in-hospital outcomes. METHODS: The Nationwide Inpatient Sample was analyzed
      for years 2000-2003. The effect of complications on in-hospital mortality, length
      of stay (LOS), and hospital charges were examined using bivariate and
      multivariable logistic and linear regression analyses. The confounding effects of
      age, sex, primary diagnosis, type of valve replacement, type of admission,
      comorbid conditions, and hospital characteristics were adjusted. RESULTS: A total
      of 43,909 patients underwent aortic valve replacement as the primary procedure
      during the study period and 16,516 patients underwent mitral valve replacement.
      Complications occurred in 35.2% of those undergoing aortic valve replacements and
      in 36.4% of those undergoing mitral valve replacements. Almost half of these are
      cardiac complications and a quarter involve hemorrhage/hematoma/seroma.
      Complications were significantly associated with in-hospital mortality, LOS, and
      hospital charges even after adjusting for patient and hospital characteristics.
      CONCLUSION: Complications are prevalent and exert a considerable influence on
      outcomes following aortic and mitral valve replacements. Quality initiatives
      should focus on minimizing complications and improving processes of care that
      would enable complications to be better resolved if they occur.

PMID- 17505441
TI  - Acute aortic insufficiency after blunt chest trauma: a case report.
AB  - Traumatic aortic valve regurgitation is a rare complication of non penetrating
      blunt chest trauma which usually requires surgical management. We describe a case
      of a 21 year old man with blunt chest trauma who was diagnosed with aortic valve
      regurgitation due to rupture of the right coronary cusp one month after falling
      from a high place. Rupture of aortic valve cusp was treated successfully with
      aortic valve replacement.

PMID- 17505442
TI  - Prosthetic replacement and tangential resection of the superior vena cava in
      chest tumors.
AB  - AIM: Infiltration of the superior vena cava (SVC) due to advanced non small cell
      lung cancer (NSCLC) or thymoma can be treated by prosthetic replacement or
      tangential resection. These two technical procedures and their results are
      described. METHODS: From 1988 to 2002, we performed 37 SVC resections: 21
      replacements with polytetrafluoroethylene (PTFE) prostheses and 16 tangential
      exereses. Sixteen patients affected by locally advanced NSCLC (12 T4; 4
      extracapsular N2) and 5 subjects with thymoma (Stage III Masaoka) underwent
      prosthetic replacement of the SVC. After neoadjuvant polychemotherapy, tangential
      resection was performed on 12 patients with extracapsular N2 NSCLC, and in 1
      patient with T4 and in 3 patients with T3a disease. We performed prosthetic
      replacement in 18 cases using a straight prosthesis (?18-20 mm). A bridge (10-14
      cm) between the innominate vein and the right atrium was created in 3 patients.
      The main indication for a prosthetic replacement was infiltration of more than
      30% of the circumference of the SVC. There were 4 thromboembolic complications
      (19%), with one intraoperative death (4.8%). Tangential resection of the SVC for
      infiltration <20% was performed both manually and with staplers (double clamping)
      without any major complications. RESULTS: Mean survival was 23 months in those
      patients who had undergone PTFE replacement for T4 lung cancer and for thymoma.
      Mean survival was 15 months in those who had undergone tangential resections for
      NSCLC with extracapsular N2. We performed restaging of the tumor using chest
      angio-CT scan in 11 patients, one year after the operation. We found 80% patency
      in 7 SVC prostheses and 50% patency in 4 others: the two bridges between the left
      innominate vein and the right atrium appeared to be partially closed but were
      compensated by important collateral circles. CONCLUSION: SVC replacement,
      associated with pulmonary resection or removal of mediastinal masses, can be
      performed in selected cases. It should not be considered as palliative treatment
      because of the important perioperative risks. SVC tangential resection involves
      fewer surgical problems. However, since this procedure is used mostly for N2
      NSCLC subjects, patients have a low mean survival in spite of adjuvant therapy.

PMID- 17505443
TI  - IIIB-T4 non-small cell lung cancer: indications and results of surgical
      treatment.
AB  - AIM: T4 non-small cell lung cancer (NSCLC) is commonly considered a
      contraindication to surgery, indeed chemo-radiotherapy achieves a poor survival
      rate. We have reviewed our experience with T4 NSCLC patients who underwent
      surgery with the aim of debating the indications and results of surgical
      treatment in this highly selected group of patients. METHODS: We investigated a
      cohort of 60 patients, 49 men and 11 women, who underwent surgery for NSCLC from
      January 1998 to December 2002 and whose pathological staging was T4N0-2M0. The
      median age was 65 years (range 46-82). The tumors were classified T4 for the
      following reasons: intralobar satellite metastasis in 24 cases, direct
      mediastinum invasion in 18 cases, malignant pleural effusion in 7 cases,
      involvement of the superior vena cava in 4 cases, marginal invasion of the
      vertebral body in 3 cases, involvement of the carena in 3 cases and invasion of
      the left atrium in 1 case. Thirteen patients had undergone neo-adjuvant
      chemotherapy while 39 underwent adjuvant therapies. RESULTS: Thirty-two patients
      resulted with N0 disease, 5 with N1 and 23 with N2 disease. Forty patients
      relapsed (27 systemic and 13 local relapses). The mean survival was 20 months. Of
      the examined parameters only metastatic nodal involvement was significantly
      associated with a worse prognosis (P=0.007). CONCLUSION: Surgery for T4 NSCLC may
      be effective in those patients without mediastinal (N2) lymph node involvement.
      The prognosis was neither affected by the subtype of T4 tumor nor by the use of
      adjuvant therapies and/or neoadjuvant chemotherapy but only by the N status. In
      the preoperative work-up, every possible effort should be made to achieve a
      careful evaluation of lymph-nodal status (primarily by mediastinoscopy and video
      operative staging).

PMID- 17505445
TI  - Pneumocephalus after Pancoast's tumor surgery: to be or not to be conservative?
AB  - We report a case of a 62-year-old man affected by Pancoast's tumor who developed
      pneumocephalus 17 days after right upper lobectomy with en bloc resection of the
      first three ribs and C8-D1 branches of the brachial plexus. The patient
      complained of aphasia, disorientation and sphincterial release. A chest and brain
      CT scan showed a right apical pneumothorax associated with a massive
      pneumocephalus of the ventricles and of the subarachnoidal spaces. A
      pneumoperitoneum was also seen. The patient was treated using pleural drainages,
      Trendelenburg's position and antibiotic therapy. Clinical and radiological
      remission was achieved after 12 days of additional hospital stay.

PMID- 17505444
TI  - Risk of mortality from cardiovascular and respiratory causes in patients with
      chronic obstructive pulmonary disease submitted to follow-up after lung resection
      for non-small cell lung cancer.
AB  - AIM: Considerable controversy surrounds mortality from non-neoplastic diseases
      during the postoperative follow-up of patients with non-small cell lung cancer
      (NSCLC) and chronic obstructive pulmonary disease (COPD). This study investigated
      the incidence of mortality from cardiovascular and respiratory (CVR) causes in
      patients with COPD submitted to follow-up after lung resection for NSCLC, and
      identified preoperative and postoperative risk factors. METHODS: A total of 398
      patients with mild or moderate COPD were followed up in our department after lung
      resection for NSCLC (median follow-up 61 months). Statistical analysis of the
      data was carried out to determine the incidence and the prognostic factors of
      postoperative death from CVR causes. RESULTS: Of the 398 resected patients, 186
      survived without tumor recurrence; 24/186 (12.9%) died of CVR causes (acute
      respiratory failure, pneumonia, pulmonary embolism, acute pulmonary edema, acute
      myocardial ischemia or stroke). These 24 patients had a higher frequency of pre
      existing coronary artery disease or heart failure (P=0.0003), predicted
      postoperative FEV1 <1000 mL (P=0.0008), exertional dyspnea (P=0.0000), and 30-day
      operative cardiopulmonary complications (P=0.001). Protective features were young
      age (<40 years), early stage disease, and minor resection (lobectomy).
      Independently significant adverse prognostic factors were stage III-IV disease
      (cumulative CVR death rate 47% at 5-10 years; P=0.028 vs. stage I-II) and
      completion pneumonectomy or partial resection of the other lung for a second
      primary tumor (cumulative CVR death rate 50% and 57%, respectively, at 5-10
      years; P=0.0016 vs. all other resections). Older age and tumor histology were
      significant risk factors only in patients with advanced stage disease.
      CONCLUSION: The findings suggest that postoperative CVR death may be expected in
      patients with COPD and advanced stage NSCLC or in those undergoing completion
      pneumonectomy or partial resection of the other lung for a second primary tumor.
      Other risk factors are previous coronary artery disease and/or heart failure,
      exertional dyspnea and predicted postoperative FEV1 <1000 mL.

PMID- 17505447
TI  - Therapy of chronic end-stage heart failure: where do we go?

PMID- 17505446
TI  - A surgical case of pulmonary adenocarcinoma complicated with pulmonary infarction
      presenting as an intrapulmonary metastasis.
AB  - Pulmonary adenocarcinoma complicated with a pulmonary infarction presenting as an
      intrapulmonary metastasis is relatively rare. We present a case of pulmonary
      infarction manifesting as intrapulmonary metastases of lung cancer. A previously
      healthy 59-year-old woman was admitted to our hospital on May 16, 2002 for
      evaluation of multiple abnormal radiographic shadows in the right lower lung
      field. Laboratory tests showed no abnormalities except for a slight elevation of
      carcinoembryonic antigens. Computed tomography of the chest revealed a hilar mass
      lesion with parenchymal lesions in the periphery of the right lower lobe, highly
      suspected to be a pulmonary adenocarcinoma with intrapulmonary metastases. A
      diagnosis of pulmonary adenocarcinoma was confirmed by a transbronchial brushing
      examination. A right middle and lower bilobectomy with mediastinal lymph node
      dissection was needed by hilum lymphadenopathy and a lower lobe invasion of the
      main tumor. Histopathological findings of the resected specimens revealed poorly
      differentiated adenocarcinoma of the lung with N1 (#11i) disease and multiple
      pulmonary infarctions with coagulation necrosis and recanalization. Pulmonary
      infarctions are demonstrated on chest x-rays as round or polygonal in shape, and
      located at the periphery of the same lobe as the primary tumor. Computed
      tomography is more sensitive than conventional radiography in the detection of
      pulmonary infarction. Our case suggests that pulmonary infarction associated with
      lung cancer should be considered as one important cause of peripheral pulmonary
      nodules.

PMID- 17505448
TI  - Pyoderma gangrenosum after sternotomy: an early presentation of lung carcinoma.

PMID- 17505449
TI  - Talc pleurodesis in the treatment of chylothorax following mitral valve
      replacement.

PMID- 17505450
TI  - [Total laparoscopic hysterectomy versus vaginal hysterectomy: a prospective
      randomized trial].
AB  - AIM: The aim of the study was to compare the effects of total laparoscopic
      hysterectomy with those of vaginal hysterectomy. METHODS: We conducted a
      prospective randomised trial on 400 patients who agreed to be randomized to
      either laparoscopic total hysterectomy or vaginal hysterectomy. They were
      monitored for one year to evaluate the rate of major complications and the
      results on quality of life. RESULTS: Total laparoscopic hysterectomy was
      associated with a higher rate of major haemorrhages and ureteric injuries than
      vaginal hysterectomy (7% vs 2.5% and 2.5% vs 0%; P<0.05) only during the first
      year of study according to a normal learning-curve. It took longer to perform
      (85.9 min vs 46.6 min), but was less painful (visual analogue scale 5.3 vs 6.0;
      P<0.01) and there was a shorter stay in hospital after the operation (2.9 vs 3.3
      days). Six weeks after the operation, total laparoscopic hysterectomy was
      associated with less pain and better quality of life than vaginal hysterectomy
      (SF-12). CONCLUSION: Total laparoscopic hysterectomy was associated with a
      significantly higher rate of major haemorrhages and ureteric injuries than
      vaginal hysterectomy only during the first year of study according to a normal
      learning-curve. It took longer to perform but was associated with less pain,
      quicker recovery, and better short term quality of life.

PMID- 17505451
TI  - [Laparoscopic hysterectomy after GnRh analogue therapy].
AB  - AIM: The aim of this clinical prospective study was to evaluate the effectiveness
      of the GnRh analogues treatment carried out before the implementation of a
      laparoscopic hysterectomy on patients affected by fibromatosis and metrorrhagia.
      METHODS: We examined a cohort of 40 women sharing an average uterine volume of
      510+/-95 cm3 observed in a time span of 22 months. Precociously, in the
      follicular phase we treated our sample of patients with only one ampoule of
      triptorelin 11.25 mg in a short-term regime. At the end of the treatment, after
      about 3 months, we re-scanned by ultrasound the uterine volume before carrying
      out the surgical treatment. RESULTS: The presurgical treatment with GnRh
      analogues allowed a significant reduction of the uterine volume of about 4% in 34
      cases (85% patients) as confirmed by ultrasound. The Student t test revealed
      significant difference before and after the treatment with a P value <0.05.
      Further, we obtained an increase of about 2-3 g of hemoglobin. The average
      treatment time was of about 130 min (ranging from 110 to 160 min). The only
      intrasurgical complication consisted in a vescical lesion which we repaired
      without consequences. In the postsurgical period we incurred in only 3 cases of
      fever (38.5 degrees C) which required an antibiotic therapy. The average length
      of hospitalization was three days. CONCLUSION: The presurgical treatment with
      GnRh analogues can be considered a valuable option in the management of the
      uterine leiomyomas pathology.

PMID- 17505452
TI  - [Laparoscopic lymphadenectomy as treatment of endometrial cancer].
AB  - AIM: This study compares the effects of laparoscopic lymphadenectomy versus those
      of abdominal lymphadenectomy in patients with endometrial cancer. METHODS: A
      prospective randomized study was performed among 80 patients randomly assigned to
      laparoscopic lymphadenectomy and to abdominal lymphadenectomy in the treatment of
      endometrial cancer. Clinical outcomes and complications were compared for 1 year
      of follow-up. RESULTS: Forty patients were assigned to laparoscopic
      lymphadenectomy and 40 patients to abdominal lymphadenectomy. The laparoscopic
      approach was associated with a longer operative time (234.1 min vs 137.3 min) but
      was less painful (VAS 5.3 vs 7.9; P<0.000) and resulted in a shorter hospital
      stay (4.4+/-1 vs 7.9+/-1.2 days; P<0.000). At 6 weeks the quality of life was
      better in patients who had laparoscopic lymphadenectomy (SF-12). CONCLUSION:
      Laparoscopic lymphadenectomy was associated with a significantly lower rate of
      major and minor postoperative complications and a better short term quality of
      life.

PMID- 17505453
TI  - The risk of premalignant and malignant pathology in endometrial polyps: should
      every polyp be resected?
AB  - AIM: There is no wide consensus in the literature on the clinical significance
      and management of symptomatic and asymptomatic polyps. Aims of the study are to
      evaluate frequency of premalignant and malignant histo-pathologic features in
      endometrial polyps resected hysteroscopically and identify clinical parameters
      able to predict final histopathologic diagnosis. METHODS: Clinical data and
      pathologic report of 90 consecutive operative hysteroscopies performed on women
      with endometrial polyps were collected. Frequency of premalignant and malignant
      histopathologic features on the polyps were calculated and relation to clinical
      risk factors analyzed. RESULTS: The frequency of premalignant and malignant
      histopathologic features in polyps was 6.7% and 2.2% respectively. Owing to the
      small sample size no statistical analysis to detect clinical risk factor for
      premalignant or malignant histopathologic features could be performed.
      CONCLUSION: Frequency of premalignant and malignant histopathologic features in
      symptomatic and asymptomatic patients is not negligible. Reported clinical risk
      factors for malignant degeneration of endometrial polypoid lesions are the same
      as those reported for endometrial cancer and are very common in patients with
      endometrial polyps. Every endometrial polyp should be resected.

PMID- 17505454
TI  - Is prenatal bonding enhanced by prenatal education courses?
AB  - AIM: Prenatal education courses (PEC) are a way of allaying anxiety in pregnancy.
      PEC consist of a series of five 1-hour lessons in the first and second trimesters
      of pregnancy. Conducted by nurses or midwives, the course syllabus includes the
      basics of fetal physiology and development, singing sessions, dance sessions,
      massage-through-the-womb sessions. Here we investigated whether they can enhance
      feto-maternal bonding. METHODS: We studied 77 pregnant women (mean age: 31.5+/
      4.1 years), 36 of whom attended PEC. We used the Prenatal Attachment Inventory
      (PAI), a validated 21-item questionnaire, to score prenatal bonding and compared
      the scores of the two groups. Three months after delivery, we asked the mothers
      to fill in another questionnaire to assess infant and maternal well-being.
      RESULTS: The PEC group showed a higher PAI score than the control group (65.5+/
      6.9 vs. 59.9+/-6.1; P<0.05). Babies born to the PEC group had a higher frequency
      of unexplained crying. CONCLUSION: PEC positively influenced prenatal attachment.
      More studies are needed to assess whether this may be useful for the development
      of the mother-infant relationship.

PMID- 17505455
TI  - Morphologic, endocrinologic and natural pregnancy assessment of intact and sliced
      ovarian orthotopic auto-implants in rabbits. Natural pregnancy and ovarian auto
      implants.
AB  - AIM: The aim of the paper was to assess the natural pregnancy of rabbits
      submitted to bilateral oophorectomy and orthotopic autologous intact and sliced
      ovarian transplantation without a vascular pedicle and to determine the
      morphofunctional aspects of the reimplanted ovaries. METHODS: Thirty-two female
      New Zealand White rabbits were studied. The ovaries were removed and
      orthotopically replaced without vascular anastomosis. In Group 1 (n=8), only
      laparotomy and laparorrhaphy were performed. In Group 2A (n=8) intact ovaries
      were reimplanted on both sides. In Group 2B (n=8) both ovaries were sliced and
      orthotopically reimplanted. In Group 2C (n=8), an intact ovary was reimplanted on
      one side and a sliced ovary on the other side. Three months later, the animals
      were paired with sexually mature males for copulation. Estradiol, progesterone,
      follicle stimulating hormone and luteinizing hormone levels were assessed. A
      histologic study of the reimplanted ovaries, tubes and uterus was carried out,
      and the number of pregnancies and litters of each group were also determined. The
      chi squared test compared the number of successful pregnancies and the number of
      litters between the groups. One-way ANOVA and the Tukey-Kramer tests compared the
      hormonal dosages. The significance was for P <0.05. RESULTS: Pregnancies occurred
      in all rabbits of Group 1 between the 2(nd) and 3(rd) months after copulation,
      with 6 to 10 litters. In Group 2, pregnancies occurred between the 5(th) and
      8(th) postoperative month. Pregnancies occurred in 37.5% of rabbits in Group 2A,
      and 50% in groups 2B and 2C. There was no difference in the number of litters
      between the reimplanted groups, with 1 to 4 litters per rabbit. Hormone levels
      and histology confirmed the vitality of all ovaries. CONCLUSION: Intact or sliced
      orthotopic autologous ovarian reimplantation without a vascular pedicle is viable
      in rabbits, and preserves their hormonal and fertile functions.

PMID- 17505456
TI  - [Perinatal transmission of HIV].
AB  - Paediatric HIV infection is still the most important pandemic, despite the
      substantial reductions of mother to child transmission achieved in North America
      and Europe. The total number of people living with the human immunodeficiency
      virus (HIV) rose in 2004 to reach its highest level ever: an estimated 39.4
      million people are living with the virus. This number has been rising in every
      region, compared with two years ago, with the steepest increases occurring in
      East Asia, in Eastern Europe and central Asia. Sub-Saharan Africa remains by far
      the worst-affected region, with 25,4 million people living with HIV at the end of
      2004. The AIDS epidemic is affecting women and girls in increasing number in
      Africa; them make up almost 57% of all people infected with HIV, but became a
      striking 76% in Sub-Saharan area. This review will focus on the current knowledge
      available regarding the timing of HIV transmission and the subsequent
      implications for its prevention. Mother to child transmission can take place
      during pregnancy, labour, delivery and post-partum, through breastfeeding.
      Different factors may influence HIV transmission during each of these time
      periods, and hence interventions to reduce transmission during each of these
      periods may also require different preventive strategies. The risk of mother to
      child transmission of HIV infection can be substantially reduced from 15-20%
      without interventions to less than 2% with the use of antiretroviral therapy
      during pregnancy, during labour and in the neonatal period, with an elective
      caesarean section delivery and refraining from breastfeeding. Factors associated
      with an increased risk of perinatal HIV transmission include advanced maternal
      blood, prolonged duration of ruptured membranes, and increased quantity of HIV in
      maternal blood at delivery.

PMID- 17505457
TI  - Perinatal infections and cerebral palsy.
AB  - Cerebral palsy (CP) is a complex disease characterized by the aberrant control of
      movement or posture that appears in early life and affect about 2 per 1000 live
      born children. CP represents the most common physical disability in childhood. An
      association between clinical chorioamnionitis and cerebral palsy has been
      recognised. Very low-birthweight infants constitute more than 1/4 of all new
      cases of cerebral palsy. The use of antimicrobial treatment of pregnant women
      with bacterial vaginosis, a complete course of antenatal steroids and magnesium
      sulphate are the most important strategies to prevent cerebral palsy.

PMID- 17505458
TI  - Viral infections in pregnancy.
AB  - Viral infections are a common complication of pregnancy and in some cases, can
      have profound effects for the unborn fetus. The human herpesvirus family is
      composed of large, enveloped DNA viruses that have close structural similarity.
      The family includes the herpes simplex viruses types 1 and 2, varicella zoster
      virus, Epstein Barr virus, cytomegalovirus (CMV), and human herpes viruses types
      6, 7 and 8. These viruses all share the ability to establish latency and
      reactivate at a later time. Structural fetal abnormalities can result from
      intrauterine infection and transmission of the infection during the pregnancy or
      at the time of delivery can result in important neonatal disease. Human
      parvovirus B19 is a DNA virus with strong tropism for erythroid precursors and
      infection during pregnancy can result in fetal hydrops and stillbirth. The
      causative agents of hepatitis are hepatotropic viruses termed hepatitis A, B, C,
      D (deltavirus) and E. All except hepatitis B virus are RNA viruses. Vertical
      transmission of maternal infection with hepatitis B and C can result in
      significant long term sequelae.

PMID- 17505459
TI  - [Diagnostic and operative fertiloscopy].
AB  - In the last decade, ''fertiloscopy'', a new mini-invasive diagnostic technique,
      is becoming more and more popular: it is a good alternative to the diagnostic
      laparoscopy, a standard procedure but surely not harmless, very often capable to
      discover pathologies in asymptomatic patients. Fertiloscopy allows the
      visualization of the posterior pelvis (posterior face of the uterus, ovaries,
      tubes and intestinal ansae with the rectum), with a technique of introducing an
      optical device in the pouch of Douglas, through the posterior vaginal fornix,
      under previous general or local anesthesia. When fertiloscopy is performed under
      local anesthesia, it can comfortably be carried out in out-patient departments
      and it is generally well tolerated by patients, who follow the whole procedure on
      the monitor. Moreover, it is possible to perform small interventions, such as
      adhesiolysis, ovarian drilling, coagulation of endometriosis spots and to perform
      chromosalpingoscopy and salpingoscopy, important investigations in the diagnostic
      iter of unexplained female infertility. With fertiloscopy, the patient,
      therefore, can avoid a real surgical intervention, such as diagnostic
      laparoscopy, and also uncomfortable examinations, such as hysterosalpingography.

PMID- 17505460
TI  - Corticosteroids for the syndrome of hemolysis, elevated liver enzymes, and low
      platelets (HELLP): what evidence?
AB  - The fundamental premise that has governed the proposal relative to the use of
      corticosteroids for the purpose of disease modification in Hemolysis, Elevated
      Liver Enzymes, and Low Platelets (HELLP) syndrome was that pre-eclampsia is a
      condition characterized by an inappropriate maternal systemic inflammatory
      response and possibly immune-mediated impairment in maternal-fetal communication,
      while corticosteroids have the capacity to exercise anti-inflammatory and
      immunosuppressive effects. The present article reviews the evidence behind this
      proposal, concluding that corticosteroids administration, either antepartum or
      postpartum, does not improve the outcome of pregnancies affected by HELLP
      syndrome. The risks associated with such an approach, especially in fetuses
      manifesting growth restriction and absent end-diastolic flow, are also discussed.
      The literature published in English between 1990 and 2006 was searched for papers
      dealing with corticosteroids treatment for disease modification in pre-eclampsia
      and HELLP syndrome, using a combination of keywords including ''HELLP syndrome
      '', ''pre-eclampsia'', ''corticosteroids'', and ''maternal and fetal outcomes''.
      The MEDLINE bibliographic database yielded 9 studies relevant to this topic,
      including one retrospective analysis, 7 randomized trials, and one meta-analysis.
      Until more convincing data become available, corticosteroids for disease
      modification in women with HELLP syndrome should not be used outside the setting
      of an approved investigational protocol.

PMID- 17505461
TI  - [Cervical cerclage and evidence-based medicine: if, how and when].
AB  - Cervical cerclage has always been the main treatment option in cases of so-called
      cervical insufficiency, a condition that is notoriously associated with a high
      risk of second trimester abortion and/or preterm delivery. We can distinguish
      between a prophylactic cerclage, to be performed electively, usually at 13-16
      weeks gestation, only when the woman has a history extremely suggestive for
      cervical incompetence (3 or more mid-trimester abortions or preterm deliveries)
      and a therapeutic cerclage. This last cerclage is recommended either for women
      who have ultrasonographic changes consistent with a short cervix or the presence
      of funneling after the 16-20 weeks gestation (urgent cerclage) and for women who
      present the asymptomatic dilation of the uterine cervix of at least 2 cm and/or a
      prolapse of the amniochorial membranes (emergent cerclage). So far there is still
      a lack of controlled and randomized trials that can unquestionably demonstrate
      the advantages of the cervical cerclage in comparison with a ''wait and see''
      aptitude. The cerclage can be performed either transvaginally, usually according
      to the McDonald technique, or transabdominally. This last approach is recommended
      when a transvaginal cerclage has to be avoided because of technical difficulties
      depending on the conditions of the cervix or when the pregnant woman has a
      history of one or more failed transvaginal cerclages. Interesting perspectives
      are currently offered by the laparoscopic cerclage, a method that has been
      effective and unexpectedly safe till now.

PMID- 17505462
TI  - Supratentorial primitive neuroectodermal tumor during pregnancy. Case report.
AB  - The case of an 18-year-old primipara in the second trimester of pregnancy
      affected by a primitive supratentorial mass is described. Main symptoms of
      increased intracranial pressure were severe headache, diplopia, and left
      hemiparesis. In the 20(th) week of pregnancy a fronto-temporal craniotomy was
      performed with complete excision of the tumor. Immunohistochemical analysis
      showed a primitive neuroectodermal tumor (PNET). Three months after being
      discharged, the patient still presented headache and apathy, and a magnetic
      resonance imaging scan again showed the presence of a temporal lesion; therefore,
      after caesarean delivery the second surgical resection of the tumor was
      performed. Combined chemotherapy and radiotherapy was required.

PMID- 17505463
TI  - Prenatal diagnosis of arthrogryposis.

PMID- 17505464
TI  - Genome-wide linkage scan of 98 bipolar pedigrees and analysis of clinical
      covariates.
AB  - Despite compelling evidence that genetic factors contribute to bipolar disorder
      (BP), attempts to identify susceptibility genes have met with limited success.
      This may be due to the genetic heterogeneity of the disorder. We sought to
      identify susceptibility loci for BP in a genome-wide linkage scan with and
      without clinical covariates that might reflect the underlying heterogeneity of
      the disorder. We genotyped 428 subjects in 98 BP families at the Center for
      Inherited Disease Research with 402 microsatellite markers. We first carried out
      a non-parametric linkage analysis with MERLIN, and then reanalyzed the data with
      LODPAL to incorporate clinical covariates for age at onset (AAO), psychosis and
      comorbid anxiety. We sought to further examine the top findings in the covariate
      analysis in an independent sample of 64 previously collected BP families. In the
      non-parametric linkage analysis, three loci were nominally significant under a
      narrow diagnostic model and seven other loci were nominally significant under a
      broader model. The top findings were on chromosomes 2q24 and 3q28. The covariate
      analyses yielded additional evidence for linkage on 3q28 with AAO in the primary
      and independent samples. Although none of the linked loci were genome-wide
      significant, their congruence with prior results and, for the covariate analyses,
      their identification in two separate samples increases the likelihood that they
      are true positives and deserve further investigation. These findings further
      demonstrate the value of considering clinical features that may reflect the
      underlying heterogeneity of disease in order to facilitate gene mapping.

PMID- 17505465
TI  - Individual differences in trait anhedonia: a structural and functional magnetic
      resonance imaging study in non-clinical subjects.
AB  - Anhedonia, the reduced capacity to gain pleasure from pleasurable experiences, is
      a key symptom of major depression and schizophrenia. Reduced hedonic capacity can
      also be measured as an enduring trait in non-clinical subjects. Such altered
      hedonic capacity is likely the result of a basic neuropsychophysiological
      dysfunction and a vulnerability marker that potentially precedes and contributes
      to the liability of developing psychiatric disorders. The characterization of the
      structural and functional neural correlates of trait anhedonia in non-clinical
      individuals may provide new insights for the early detection of such psychiatric
      diseases. Twenty-nine non-clinical subjects were scanned at the Montreal
      Neurological Institute. Trait anhedonia was measured using the Chapman Revised
      Physical Anhedonia Scale. Semi-automated and automated structural MRI
      segmentation techniques were used to explore structural correlates of trait
      anhedonia. Seventeen of the 29 subjects also underwent a functional imaging task
      where responses to the viewing of affective stimuli were examined to identify the
      functional correlates of trait anhedonia. Trait anhedonia was inversely related
      to anterior caudate volume, but positively related to ventromedial prefrontal
      cortex activity during the processing of positive information. These findings may
      reflect a specific kind of vulnerability for the development of psychiatric
      affective disorders and suggest that trait anhedonia may be linked to a
      volumetric reduction in the basal ganglia and to a prefrontal functional
      abnormality during hedonic processing.

PMID- 17505467
TI  - Neuroanatomical and cellular substrates of hypergrooming induced by
      microinjection of oxytocin in central nucleus of amygdala, an experimental model
      of compulsive behavior.
AB  - Oxytocin (OT) is a neurosecretory nonapeptide synthesized in hypothalamic cells
      that project to the neurohypophysis as well as to widely distributed sites in the
      central nervous system. Central OT microinjections induce a variety of cognitive,
      sexual, reproductive, grooming and affiliative behaviors in animals. Obsessive
      compulsive disorder (OCD) includes a range of cognitive and behavioral symptoms
      that bear some relationship with OT. Here, we study the neuroanatomical and
      cellular substrates of the hypergrooming induced by administration of OT in the
      central nucleus of amygdala (CeA). In this context, this hypergrooming is
      considered as a model of compulsive behavior. Our data suggest a link between the
      CeA and the hypothalamic grooming area (HGA). The HGA includes parts of the
      paraventricular nucleus and the dorsal hypothalamic area. Our data on
      colocalization of OT (immunohistochemistry for peptide), OT receptor (binding
      assay) and its retrogradely labeled cells after Fluoro-Gold injection in the CeA
      suggest that CeA and connections are important substrates of the circuit
      underlying this OT-dependent compulsive behavioral pattern.

PMID- 17505466
TI  - Abnormal melatonin synthesis in autism spectrum disorders.
AB  - Melatonin is produced in the dark by the pineal gland and is a key regulator of
      circadian and seasonal rhythms. A low melatonin level has been reported in
      individuals with autism spectrum disorders (ASD), but the underlying cause of
      this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin
      synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes,
      deleted in several individuals with ASD. In this study, we sequenced all ASMT
      exons and promoters in individuals with ASD (n=250) and compared the allelic
      frequencies with controls (n=255). Non-conservative variations of ASMT were
      identified, including a splicing mutation present in two families with ASD, but
      not in controls. Two polymorphisms located in the promoter (rs4446909 and
      rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were
      associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2
      x 10(-10)). Biochemical analyses performed on blood platelets and/or cultured
      cells revealed a highly significant decrease in ASMT activity (P=2 x 10(-12)) and
      melatonin level (P=3 x 10(-11)) in individuals with ASD. These results indicate
      that a low melatonin level, caused by a primary deficit in ASMT activity, is a
      risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and
      highlight the crucial role of melatonin in human cognition and behavior.

PMID- 17505468
TI  - A region of 35 kb containing the trace amine associate receptor 6 (TAAR6) gene is
      associated with schizophrenia in the Irish study of high-density schizophrenia
      families.
AB  - The TAAR6 gene has been previously associated with schizophrenia in 192 pedigrees
      of European and African ancestry. To replicate these findings we performed an
      association study of TAAR6 in 265 pedigrees of the Irish Study of High-Density
      Schizophrenia Families (ISHDSF). Of the 24 genotyped single-nucleotide
      polymorphisms only rs12189813 and rs9389011 provided single-marker evidence for
      association (0.0094<or=P<or=0.03). Two-marker haplotypes (rs7772821 and
      rs12189813; 0.0071<or=P<or=0.0023) and four-marker haplotypes (rs8192622,
      rs7772821, rs12189813 and rs9389011; 0.0047<or=P<or=0.018) gave strongest
      evidence for association. The associated high-risk (HR) haplotype in the ISHDSF
      is defined by the major alleles at rs7772821 and rs12189813
      (0.00097<or=P<or=0.023). The associated HR remains positive in a case only test
      of association by Operational Criteria score analysis in which significant
      association was observed only with the highest threshold for delusions (P<0.009).
      When analysis was restricted to affected individuals under the core schizophrenia
      (D2) diagnosis, the observed associations for HR were most significant in the
      highest threshold for delusions (P<0.004) and hallucinations (P<0.0004),
      supporting the family-based association with schizophrenia.

PMID- 17505469
TI  - The influence of blood on in vivo adenovirus bio-distribution and transduction.
AB  - Intravascular delivery of adenovirus (Ad) vectors is being developed for liver
      directed gene therapy for targeting disseminated disease in cancer therapeutics
      and for targeting non-hepatic tissues and organs through vector engineering
      strategies. The utility of Ad vectors is not limited to serotype 5 (Ad5), and
      many alternate human serotypes and non-human serotypes of Ad are currently being
      investigated. Critical to intravascular delivery of Ad is the interaction of the
      virus with host blood cells and plasma proteins, because immediate contact is
      observed following injection. Although incompletely understood, recent studies
      suggest that these interactions are critical in dictating the particle bio
      distribution and resulting transduction properties of Ad in vivo. For example,
      plasma proteins-in particular, vitamin K-dependent coagulation zymogens-are able
      to directly bind to Ad, and "bridge" the virus to receptors in the liver.
      Unraveling and characterizing these mechanisms will be of fundamental importance
      both for understanding basic Ad biology in vivo and for refinement and
      optimization of Ad vectors for human gene therapy.

PMID- 17505470
TI  - Improved retinal transduction in vivo and photoreceptor-specific transgene
      expression using adenovirus vectors with modified penton base.
AB  - Adenovirus (Ad) vectors can be injected into human ocular tissues without
      producing adverse events and are therefore a promising means of gene transfer to
      the retina. However, when administered subretinally, Ad vectors primarily
      transduce the retinal pigment epithelium (RPE), whereas the majority of mutant
      gene products that cause photoreceptor (PR) degeneration are expressed
      exclusively in the PR cells. While it has been shown previously that pseudotyping
      of Ad can partially overcome the limited PR transduction by Ad5, we found that
      pseudotyping of Ad is not necessary for transduction of PR cells. We determined
      that, in the context of Ad, the cytomegalovirus (CMV) promoter is not
      significantly active in PRs. We compared expression levels from CMV and chicken
      beta actin (CBA) promoters in neural retina and found that CBA has a 173-fold
      greater potency than CMV. We also investigated the nature of the Ad-RPE
      interaction in murine retina and determined that the RGD domain in Ad penton
      plays a key role in RPE tropism. Deletion of the RGD domain coupled with use of
      the CBA promoter permitted transgene expression in neural retina approximately
      667 times more efficiently than with Ad5 vectors. The use of these vectors in
      combination with a 4.7 kilobase (kb) rhodopsin promoter enabled transgene
      expression exclusively in PR cells in vivo.

PMID- 17505471
TI  - Spinal muscular atrophy: SMN2 pre-mRNA splicing corrected by a U7 snRNA
      derivative carrying a splicing enhancer sequence.
AB  - Spinal muscular atrophy (SMA) is a lethal hereditary disease caused by homozygous
      deletion/inactivation of the survival of motoneuron 1 (SMN1) gene. The nearby
      SMN2 gene, despite its identical coding capacity, is only an incomplete
      substitute, because a single nucleotide difference impairs the inclusion of its
      seventh exon in the messenger RNA (mRNA). This splicing defect can be corrected
      (transiently) by specially designed oligonucleotides. Here we have developed a
      more permanent correction strategy based on bifunctional U7 small nuclear RNAs
      (snRNAs). These carry both an antisense sequence that allows specific binding to
      exon 7 and a splicing enhancer sequence that will improve the recognition of the
      targeted exon. When expression cassettes for these RNAs are stably introduced
      into cells, the U7 snRNAs become incorporated into small nuclear
      ribonucleoprotein (snRNP) particles that will induce a durable splicing
      correction. We have optimized this strategy to the point that virtually all SMN2
      pre-mRNA becomes correctly spliced. In fibroblasts from an SMA patient, this
      approach induces a prolonged restoration of SMN protein and ensures its correct
      localization to discrete nuclear foci (gems).

PMID- 17505472
TI  - Tissue-specific aberrations of gene expression in HPRT-deficient mice: functional
      complexity in a monogenic disease?
AB  - We have used the hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme
      deficient mouse model of human Lesch-Nyhan disease (LND) to examine the tissue
      specificity of altered global gene expression in a genetically "simple" monogenic
      human disease. We have identified a number of genes and gene families whose
      expression is aberrant in the mouse knockout model of the LND, and we have
      identified different patterns of aberrant gene expression in two principal target
      tissues associated with the disease phenotype, i.e., the central nervous system
      and the liver. The major neurological phenotype reflects dysfunction of the
      dopamine neurotransmitter system in the basal ganglia, and we have now identified
      aberrant expression of a small number of genes in HPRT-deficient striata. The
      abnormal metabolic phenotype of hyperuricemia in HPRT-deficient mice is also
      reflected in an aberrant gene expression in the liver. We interpret these
      findings to suggest that the genetic consequences of a primary HPRT knockout in
      the mouse produces transcriptional aberrations in a number of other genes that
      may play a role in the disease phenotype. Knowledge of these secondary genetic
      defects may help in the identification of targets for drug- and gene-based
      therapy.

PMID- 17505473
TI  - The RAS/Raf1/MEK/ERK signaling pathway facilitates VSV-mediated oncolysis:
      implication for the defective interferon response in cancer cells.
AB  - Vesicular stomatitis virus (VSV) can replicate in malignant cells more
      efficiently than in normal cells. Although the selective replication appears to
      be caused by defects in the interferon (IFN) system in malignant cells, the
      mechanisms which render these cells less responsive to IFN remain poorly
      understood. Here we present evidence that an activated RAS/Raf1/MEK/ERK pathway
      plays a critical role in the defects. NIH 3T3 or human primary cells stably
      expressing active RAS or Raf1 were rapidly killed by VSV. Although IFNalpha
      treatment no longer protected the RAS- or Raf1-overexpressing cells from VSV
      infection, responsiveness to IFNalpha was restored following treatment with the
      mitogen-activated protein kinase kinase (MEK) inhibitor U0126. Similarly, human
      cancer-derived cell lines became more responsive to IFNalpha in conjunction with
      U0126 treatment. Intriguingly, dual treatment with both IFNalpha and U0126
      severely reduced the levels of viral RNAs in the infected cells. Moreover, cancer
      cells showed defects in inducing an IFNalpha-responsive factor, MxA, which is
      known to block VSV RNA synthesis, and U0126 restored the MxA expression. Our
      observations suggest that activation of the extracellular signal-regulated
      protein kinase (ERK) signaling leads to the defect in IFNalpha-mediated
      upregulation of MxA protein, which facilitates VSV oncolysis. In view of the fact
      that 30% of all cancers have constitutive activation of the RAS/Raf1/MEK/ERK
      pathway, VSV would be an ideal oncolytic virus for targeting such cancers.

PMID- 17505474
TI  - The suicide gene therapy challenge: how to improve a successful gene therapy
      approach.
AB  - The transfer of a suicide gene into donor lymphocytes to control alloreactivity
      in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      represents the widest clinical application of T-cell based gene transfer, as
      shown by more than 100 patients treated worldwide to date, several phase I-II
      studies completed, and a registrative phase III study, sponsored by a biotech
      firm, about to begin. In this mini-review, we will summarize the clinical results
      obtained to date, and attempt to identify the steps envisaged to optimize the
      suicide gene therapy approach.

PMID- 17505475
TI  - Efficacy of helper-dependent adenovirus vector-mediated gene therapy in murine
      glycogen storage disease type Ia.
AB  - Genetic deficiency of glucose-6-phosphatase (G6Pase) underlies glycogen storage
      disease type Ia (GSD-Ia, also known as von Gierke disease; MIM 232200), an
      autosomal recessive disorder of metabolism associated with life-threatening
      hypoglycemia and growth retardation. We tested whether helper-dependent
      adenovirus (HDAd)-mediated hepatic delivery of G6Pase would lead to prolonged
      survival and sustained correction of the metabolic abnormalities in G6Pase
      knockout (KO) mice, a model for a severe form of GSD-Ia. An HDAd vector encoding
      G6Pase was administered intravenously (2 or 5 x 10(12)vector particles/kg) to 2
      week-old (w.o.) G6Pase-KO mice. Following HDAd vector administration survival was
      prolonged to a median of 7 months, in contrast to untreated affected mice that
      did not survive past 3 weeks of age. G6Pase levels increased more than tenfold
      between 3 days and 28 weeks after HDAd injection (P < 0.03). The weights of
      untreated 2 w.o. G6Pase-KO mice were approximately half those of their unaffected
      littermates, and treatment stimulated their growth to the size of wild-type mice.
      Severe hypoglycemia and hypercholesterolemia, which are hallmarks of GSD-Ia both
      in humans and in mice, were also restored to normalcy by the treatment. Glycogen
      accumulation in the liver was markedly reduced. The efficacy of HDAd-G6Pase
      treatment in reversing the physiological and biochemical abnormalities associated
      with GSD-Ia in affected G6Pase-KO mice justifies further preclinical evaluation
      in murine and canine models of GSD-Ia.

PMID- 17505476
TI  - Inhibition of hepatitis C virus infection in cell culture by small interfering
      RNAs.
AB  - Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and
      hepatocellular carcinoma, yet fully efficacious treatments are missing. In this
      study, we investigated RNA interference (RNAi), a specific gene silencing process
      mediated by small interfering RNA (siRNA) duplexes, as an antiviral strategy
      against HCV. Synthetic siRNAs were designed to target conserved sequences of the
      HCV 5' nontranslated region (NTR) located in a functional, stem-loop structured
      domain of the HCV internal ribosome entry site (IRES), which is crucial for
      initiation of polyprotein translation. Several siRNAs dramatically reduced or
      even abrogated the replication of selectable subgenomic HCV replicons upon
      cotransfection of human hepatoma cells with viral target and siRNAs, or upon
      transfection of cells supporting autonomous replication of HCV replicon with
      siRNAs. Importantly, three siRNAs also proved capable of strongly inhibiting
      virus production in cell culture. One siRNA, targeting a sequence that is highly
      conserved across all genotypes and forms a critical pseudoknot structure involved
      in translation, was identified as the most promising therapeutic candidate. These
      results indicate that the HCV life cycle can be efficiently blocked by using
      properly-designed siRNAs that target functionally important, highly conserved
      sequences of the HCV IRES. This finding offers a novel approach towards
      developing IRES-based antiviral treatment for chronic HCV infections.

PMID- 17505477
TI  - Expression of mutated huntingtin fragment in the putamen is sufficient to produce
      abnormal movement in non-human primates.
AB  - Huntington's disease (HD) is a neurological disorder characterized by striatal
      degeneration, motor symptoms and complex neuropsychiatric alterations. There is
      currently no genetic model of HD in non-human primates (NHPs). In this study we
      investigated neuropathological and behavioral changes following injections of
      lentiviral vectors encoding a fragment of mutated huntingtin (Htt171-82Q) into
      the dorsolateral sensorimotor putamen of macaques. In the first study, we
      injected Htt171-82Q into one hemisphere and a lentiviral vector encoding Htt171
      19Q or saline into the other, and studied the animals for 9 weeks. During this
      period, when apomorphine was administered into Htt171-19Q/82Q animals, it induced
      progressive chorea, dystonia and ipsilateral turning behavior, whereas animals
      infected with Htt171-19Q/19Q showed no abnormal behavior. After 9 weeks, the
      putamen of animals infected with Htt171-82Q presented neuritic and nuclear Htt
      aggregates, reactive astrocytes and loss of the neuronal marker NeuN. In a second
      study, we injected Htt171-82Q bilaterally into the dorsolateral putamen. From
      week 15 after infection, these animals progressively developed spontaneous
      dyskinesia of the legs, arms, and trunk and, in one case, tics that persisted for
      up to 30 weeks. The present study constitutes a proof-of-principle for the
      development of a genetic model of HD in NHP.

PMID- 17505478
TI  - Lentiviral vectors mediate stable and efficient gene delivery into primary murine
      natural killer cells.
AB  - Natural killer (NK) cells are lymphocytes that provide an important line of
      defense against many types of microorganisms, viruses and tumors. The development
      of an efficient gene transfer system for genetically modifying primary murine NK
      cells will facilitate the studies of NK cell differentiation, acquisition of self
      tolerance, and induction of anti-tumor responses. In this study we used an
      enhanced green fluorescent protein (EGFP)-expressing vector to carry out a
      systematic evaluation of the efficiency of lentiviral transduction of primary
      murine NK cells with or without prior interleukin-2 (IL-2) activation. In a
      single-step transduction protocol, we demonstrated that human immunodeficiency
      virus type 1-based lentiviral vectors support an average of 40% transduction
      efficiency on primary NK cells. These genetically modified NK cells are found to
      maintain stable EGFP transgene expression in vitro, and can be further expanded
      in IL-2 supplemented culture medium. Lentiviral transduction does not affect NK
      surface phenotypes or functions (apoptosis, cytokine production and
      cytotoxicity). We further demonstrated efficient gene transfer into
      differentiating NK cells derived from the lentiviral-transduced murine
      hematopoietic progenitor cells in vitro. This study therefore establishes a
      simple and efficient approach to the genetic engineering of primary murine NK
      cells, and will prove useful in studying basic NK cell biology and in exploring
      the therapeutic potential of NK cells in inbred and transgenic mouse models.

PMID- 17505479
TI  - Lentiviral gene delivery of vMIP-II to transplanted endothelial cells and
      endothelial progenitors is proangiogenic in vivo.
AB  - Therapies that stimulate angiogenesis show promise in revascularization of
      transplanted or ischemic tissues. Viral macrophage inflammatory protein-II (vMIP
      II) is encoded by human herpesvirus 8, and it can be both immunosuppressive and
      proangiogenic. However, little has been done to characterize the potential of
      vMIP-II-induced angiogenesis. We engineered a vMIP-II lentiviral gene vector,
      transduced both mature endothelial cells and progenitors, and transplanted these
      in Matrigel templates as an in vivo angiogenesis model. Our results show that
      vMIP-II promotes new, functional, branching, and segmented vessels associated
      with smooth muscle cells and connected with the host vasculature. Angiogenesis is
      enhanced through host cells as well as through transplanted vMIP-expressing
      endothelial cells. As a proof-of-concept for using vMIP-II in clinical
      applications, we showed that islets co-transplanted with endothelial cells
      expressing vMIP-II were revascularized and survived in Matrigel templates,
      whereas no islets survived under control conditions. vMIP-II up-regulates the
      expression of multiple proangiogenic factors that can have a synergistic effect.
      These include vascular endothelial growth factor (VEGF), kinase insert domain
      receptor, neuropilin 2, carcinoembryonic antigen-related cell adhesion molecule
      1, interleukin-1alpha, fibronectin, and integrins alpha3, alpha4, and alpha5.
      These results provide the first demonstration that vMIP-II is proangiogenic in
      vivo and can deliver this function to endothelial progenitors as well as to
      mature endothelial cells through vector-mediated gene delivery.

PMID- 17505480
TI  - Lentiviral vectors with CMV or MHCII promoters administered in vivo: immune
      reactivity versus persistence of expression.
AB  - Lentiviral vectors (LVs) are potential tools for genetic vaccination. To improve
      the safety of LV vaccines, we evaluated the selectivity, bio-distribution,
      persistence of expression, and immune potency of vesicular stomatitis virus G
      (VSV-G)-pseudotyped vectors transcriptionally targeted to antigen presenting
      cells (APCs) through a major histocompatibility complex class II (MHCII)
      promoter. Control vectors contained the ubiquitous cytomegalovirus (CMV)
      promoter. Bio-distribution studies after intravenous injections of LVs expressing
      green fluorescent protein (GFP) or luciferase were conducted by a combination of
      flow cytometry, immunofluorescence, real-time quantitative polymerase chain
      reaction (RT-Q-PCR) and whole-body bioluminescence analyses. GFP-expressing
      vectors showed selective expression in MHCII(+) cells of spleen and LV-CMV-GFP
      administration produced noticeable spleen inflammation, whereas LV-MHCII-GFP did
      not. Long-term optical imaging analyses of C57BL/6 mice injected with LV-CMV-LUC
      showed diminishing luciferase expression in the liver and spleen over time.
      Vaccination/boost with LV-CMV expressing the melanoma antigen tyrosinase-related
      protein 2 (TRP2) yielded dose-dependent antigen-specific CD8(+) T-cell reactivity
      and high protection against B16 melanoma challenge. Unexpectedly, administration
      of LVs containing the MHCII promoter resulted in persistence of luciferase
      expression and viral integration in MHCII(+) splenocytes and virtually no CD8(+)
      T-cell responses against TRP2. These studies reveal that APC transduction by LVs
      could lead to immune reactivity (LV-CMV) or persistence of transgene expression
      (LV-MHCII), providing a relevant paradigm for vaccination and gene replacement
      approaches.

PMID- 17505481
TI  - Current status of cardiovascular gene therapy.
AB  - Gene transfer for the therapeutic modulation of cardiovascular diseases is an
      expanding area of gene therapy. During the last decade several approaches have
      been designed for the treatment of hyperlipidemias, post-angioplasty restenosis,
      hypertension, and heart failure, and for protection of vascular by-pass grafts
      and promotion of therapeutic angiogenesis. Adenoviruses (Ads) and adeno
      associated viruses (AAVs) are currently the most efficient vectors for delivering
      therapeutic genes into the cardiovascular system. Gene transfer using local gene
      delivery techniques have been shown to be superior to less-targeted intra
      arterial or intra-venous applications. To date, no gene therapy drugs have been
      approved for clinical use in cardiovascular applications. In preclinical studies
      of therapeutic angiogenesis, various growth factors such as vascular endothelial
      growth factors (VEGFs) and fibroblast growth factors (FGFs), have shown positive
      results. Gene therapy also appears to have potential clinical applications in
      improving the patency of vascular grafts and in treating heart failure. Post
      angioplasty restenosis, hypertension, and hyperlipidemias (excluding homozygotic
      familial hypercholesterolemia) can usually be managed satisfactorily by
      conventional approaches, and are therefore less favored areas for gene therapy.
      The development of technologies that can ensure long-term, targeted, and
      regulated gene transfer, and a careful selection of target patient populations,
      will be very important for the progress of cardiovascular gene therapy in
      clinical applications.

PMID- 17505482
TI  - In vivo study of HIV-1 Tat arginine-rich motif unveils its transport properties.
AB  - Tat-derived peptides have attracted much interest as molecular carriers for
      intracellular delivery as they incorporate specific attributes required for
      efficient cargo delivery to sub-cellular domains. Little is known, however, about
      intracellular trafficking and interactions of Tat peptide-tagged cargoes,
      although some in vitro studies have suggested the relevance of active processes
      in Tat peptide-driven nuclear translocation. These issues are addressed by
      comparing Tat peptide-induced transport properties with well-established passive
      diffusion and active import benchmarks in living cells. Specifically, we examine
      several constructs of increasing molecular weight (MW) both below and above the
      threshold for passive diffusion through the nuclear pore. The resulting sub
      cellular localization is analyzed by confocal imaging, and construct
      intracellular dynamics is investigated by fluorescence recovery after
      photobleaching (FRAP) real-time imaging. Our experiments yield the characteristic
      transport parameters of Tat peptide intra-cytoplasm dynamics and
      nucleus/cytoplasm shuttling. These results allow us to elucidate the mechanism of
      Tat peptide-driven nuclear permeation, demonstrating that it crosses the nuclear
      envelope (NE) by passive diffusion. Finally, we discuss the limitations of this
      route in terms of acceptable cargo size.

PMID- 17505483
TI  - Development and validation of a robust and versatile one-plasmid regulated gene
      expression system.
AB  - We have developed a one-plasmid regulated gene expression system, pBRES, based on
      a mifepristone (MFP)-inducible two-plasmid system. The various expression
      elements of the pBRES system (promoters, 5' and 3' untranslated regions (UTRs),
      introns, target gene, and polyA sequences) are bounded by restriction enzyme
      sites so that each module can be conveniently replaced by alternate DNA elements
      in order to tailor the system for particular tissues, organs, or conditions.
      There are four possible orientations of the two expression units relative to each
      other, and insertion of a variety of expression elements and target genes into
      the four different orientations revealed orientation- and gene-dependent effects
      on induced and uninduced levels of gene expression. Induced target gene
      expression from the pBRES system was shown to be comparable to the two-plasmid
      system and higher than the expression from the cytomegalovirus (CMV) promoter in
      vivo, while maintaining low uninduced levels of expression. Finally, a pBRES
      expression cassette was transferred to an adeno-associated virus (AAV) vector and
      shown to be capable of regulated gene expression in vivo for nearly 1 year.

PMID- 17505484
TI  - A high throughput in vivo model for testing delivery and antiviral effects of
      siRNAs in vertebrates.
AB  - Despite the promise of small interfering RNAs (siRNAs) in antiviral therapy, few
      in vivostudies of them as inhibitors of viral replication and disease have been
      published, a lack that is most probably due to problems with obtaining successful
      delivery. Here we introduce a novel in vivomodel composed of small juvenile
      rainbow trout and a fish pathogenic virus to analyze the delivery and antiviral
      effects of formulated siRNAs. Intraperitoneally (IP) injected siRNAs formulated
      in polycationic liposomes, and to a lesser degree naked siRNAs, primarily entered
      free IP cells, including macrophage-like cells. Uptake in these cells correlated
      with antiviral activity, seen as reduced mortality of virus-challenged fish.
      However, protection at the disease level was not dependent upon which of three
      tested siRNAs was used, and protection correlated with up-regulation of an
      interferon (IFN)-related gene in the liver, indicating a systemic IFN response.
      The results emphasize the compromise in using transfection reagents for improved
      uptake of siRNAs, where these reagents also increase the risk of the siRNAs
      ending up in a cellular compartment in which stimulation of non-specific anti
      viral defence mechanisms will be initiated.

PMID- 17505485
TI  - Increased sensitivity of radiated murine cervical cancer tumors to E7 subunit
      vaccine-driven CTL-mediated killing induces synergistic anti-tumor activity.
AB  - The development of therapeutic vaccines has important implications for the
      treatment of cancer patients. Here we investigate whether human papillomavirus
      (HPV) E7 subunit vaccines can enhance tumor radioresponse using an established
      cervical cancer animal model. Radiation plus E7 subunit vaccines improved
      complete response, cure, and recurrence rates of tumors dramatically compared
      with single therapy alone. In particular, both components of the E7 subunit
      vaccines (E7 protein and CpG-oligodeoxynucleotide) were required for the
      induction of antigen (Ag)-specific cytotoxic T-lymphocyte (CTL) responses and for
      therapeutic synergy with radiotherapy. Moreover, with combined therapy the
      radiation dose could be reduced by 16 Gy to achieve an equivalent anti-tumor
      efficacy to radiation treatment alone. This therapeutic synergy was found to be
      mediated by CD8(+) CTLs and was concomitant with histological changes (presence
      of apoptotic bodies and multinucleated giant cells; heavy infiltration of
      lymphocytes), as determined by in vivo T-cell depletion and histological
      analysis. Finally, phenotypic changes of radiated tumors and their increased
      sensitivity to CTL-mediated killing appeared to be responsible for therapeutic
      synergy. These results show that E7 subunit vaccines act as a potent enhancer of
      tumor radioresponse and that this is mediated by increased sensitivity of
      radiated tumors to CTL-mediated killing. This study further suggests that E7
      targeted therapeutic vaccines have the potential to improve radiotherapy in
      patients with cervical cancer.

PMID- 17505487
TI  - Clinical pharmacology: bridging discovery and practice.

PMID- 17505491
TI  - In vivo molecular imaging biomarkers: clinical pharmacology's new "PET"?
AB  - Medicine, including the pharmaceutical and biotechnology industries as well as
      many clinical practitioners, has recognized the importance of using molecular
      imaging biomarkers, including those labeled in such a way as to be imaged by
      positron emission tomography (PET), as tools for predicting outcomes in drug
      development and creating opportunities for "personalized" medicine, for
      diagnosing early-stage disease, and for the follow-up of the effectiveness of
      treatment.(1) However, only one important and widely used PET biomarker is
      currently approved by the Food and Drug Administration (FDA). If the technology
      is so important, we can ask why there is such a limitation to the availability of
      these biomarkers.

PMID- 17505492
TI  - Prosecution of physicians for prescribing opioids to patients.
AB  - In this issue, Reidenberg and Willis(1) highlight the legal dangers associated
      with prescribing opioids for patients when federal or state governments believe
      that such prescribing is outside the "usual course of medical practice." This
      article expands on the themes identified by the authors and addresses the
      problems faced by both prescribers and patients when "Big Brother" enters the
      treatment room and looks over the physician's shoulder.

PMID- 17505493
TI  - Can state medical boards adequately respond to reports that physicians are
      inappropriately prescribing opioids?
AB  - In this issue, Reidenberg and Willis share results of a 2-year study of cases in
      which physicians were criminally prosecuted for their prescribing of opioids
      "outside the bounds of proper medical practice."(1) They found that in only two
      of 32 such cases had a state medical board reviewed the case before indictment.
      In many of the cases, the authors argue that the prosecutors overreached and that
      these kinds of cases could be better handled by referral to state medical boards.

PMID- 17505494
TI  - "Personalized medicine: elusive dream or imminent reality?": A commentary.
AB  - I was invited to comment on the article in this issue by Larry Lesko,
      "Personalized Medicine: Elusive Dream or Imminent Reality?",(1) especially with
      respect to three questions. There are several possible approaches to discussing
      these questions. One is to simply answer the question as directly and succinctly
      as possible; another is to expand on the questions. For the purpose of this
      Commentary, I try to do both.

PMID- 17505495
TI  - The DEA's Balancing Act to Ensure Public Health and Safety.
AB  - In their article in this issue, Reidenberg and Willis assert that there are
      multiple barriers to the adequate treatment of pain and that one of these
      barriers is fear of government action against a physician who prescribes opioids
      for patients in pain.(1) At the same time, the authors state that the risk of a
      physician's being punished by either a state medical board or the Drug
      Enforcement Administration (DEA) for a patient in pain with adequate medical
      record documentation is very small.

PMID- 17505496
TI  - Personalized medicine: elusive dream or imminent reality?
AB  - The market for molecular diagnostic tests is predicted to grow at extraordinary
      rates over the next 10 years, fueled by pharmacogenetics and the elusive dream of
      personalized medicine. The challenge is managing the expectations of the medical
      community and the public at large that have already been set by speculation,
      promises, and the repeated exposure to headlines about genetic discoveries.
      Personalized medicine is a paradigm that exists more in conceptual terms than in
      reality, with only a few marketed drug-test companion products and not very many
      actual clinical practices set up to personalize medicine in the way that
      supporters have intended. Nevertheless, the reality of personalized medicine has
      become more imminent because of the increased awareness of the shortcomings in
      the delivery of drugs with adequate benefit/risk to patients, a better molecular
      understanding of how to optimize drug selection and dosing, and an increased
      demand for integrating more clinically relevant genetic information into the drug
      development process to improve both innovation and productivity. This paper
      focuses on personalized medicine by (1) looking at some converging changes taking
      place in the health-care landscape that are creating a scientific and social
      infrastructure to enable personalized medicine, (2) considering challenges that
      need to be addressed with regard to clinical evidence standards for validating
      genotype-phenotype associations, and (3) considering how clinical pharmacology
      can help construct a rational personalized medicine framework. As therapeutic
      experts, clinical pharmacologists can work to assure that "good therapeutics
      follows good diagnostics". They are well equipped to provide timely genetic
      education to others and to interpret genetic data so that actionable decisions,
      especially about drug dosing in individual patients, can be implemented in
      clinical practice.

PMID- 17505499
TI  - A brain-derived neurotrophic factor (BDNF) haplotype is associated with
      antidepressant treatment outcome in mood disorders.
AB  - Brain-derived neurotrophic factor (BDNF) has been studied extensively in relation
      to the susceptibility to mood disorders (MD), although it remains to be clarified
      whether BDNF is a susceptibility locus for MD phenotypes, including therapeutic
      response to antidepressants. We have performed a single-marker and haplotype
      association study of eight TagSNPs polymorphisms in the genomic region containing
      the BDNF gene in 342 control subjects and 374 patients with MD, and have tested
      the association with antidepressant treatment outcome. None of the eight single
      nucleotide polymorphisms (TagSNPs) was significantly associated with MD phenotype
      after Bonferroni correction. In the single-marker analysis, a SNP was found to be
      associated with the patient's state of 'remitter' after adequate trial with a
      single antidepressant phenotype (odds ratio (OR)=2.95; P=0.0025). We also
      identified a haplotype associated with this phenotype. This study supports the
      implication of BDNF in antidepressant treatment outcome in MD, with specific
      association with 5' upstream region of BDNF gene.

PMID- 17505500
TI  - Whole genome expression profiling of hepatitis B virus-transfected cell line
      reveals the potential targets of anti-HBV drugs.
AB  - Hepatitis B virus (HBV) infection is a major health concern world wide, and few
      effective treatments have been developed. It has recently been reported that
      inhibiting host-cell proteins can prevent viral infection. The human genome may
      contain more genes required for HBV infection and replication than the viral
      genome. A systematic approach to find these potential antiviral targets is by
      host gene expression analysis using DNA microarrays. The aim of this study was to
      identify and validate novel cellular anti-HBV targets. The Human Whole Genome
      Bioarray was used to analyze differentially expressed genes in HepG2.2.15 cells
      and HepG2 cells. Altered gene expression in HepG2.2.15 cells was studied
      following treatment with the anti-HBV drug, lamivudine. Genes that were
      differentially expressed during HBV infection and reversed with anti-HBV drugs
      were validated by semiquantitative reverse transcription-PCR. Bioinformatics
      analysis revealed ABHD2, EREG, ACVR2B, CDC34, KHDRBS3 and RORA as potential
      cellular anti-HBV targets. Antisense oligodeoxynucleotides were used to test the
      antiviral activity of these potential targets. Results strongly suggested that
      inhibition of ABHD2 or EREG significantly blocked HBV propagation in HepG2.2.15
      cells. This study demonstrates that ABHD2 and EREG are essential for HBV
      propagation and provides strong evidence that these proteins could be used as
      potential targets for anti-HBV drugs.

PMID- 17505501
TI  - Genome-wide pharmacogenetic investigation of a hepatic adverse event without
      clinical signs of immunopathology suggests an underlying immune pathogenesis.
AB  - One of the major goals of pharmacogenetics is to elucidate mechanisms and
      identify patients at increased risk of adverse events (AEs). To date, however,
      there have been only a few successful examples of this type of approach. In this
      paper, we describe a retrospective case-control pharmacogenetic study of an AE of
      unknown mechanism, characterized by elevated levels of serum alanine
      aminotransferase (ALAT) during long-term treatment with the oral direct thrombin
      inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls
      and included both a genome-wide tag single nucleotide polymorphism and large
      scale candidate gene analysis. A strong genetic association between elevated ALAT
      and the MHC alleles DRB1(*)07 and DQA1(*)02 was discovered and replicated,
      suggesting a possible immune pathogenesis. Consistent with this hypothesis,
      immunological studies suggest that ximelagatran may have the ability to act as a
      contact sensitizer, and hence be able to stimulate an adaptive immune response.

PMID- 17505502
TI  - Modeling framework for human exposure assessment.
AB  - We are at the dawn of a new era of quantitative consumer exposure and risk
      assessment of chemicals driven by regulatory mandates. This remarkable
      development also signals the beginning of a dramatic resurgence in the need for
      and development of human exposure models. This paper presents some of the
      philosophical background underlying exposure modeling in the context of human
      health risk assessment. The basic types of and structure of inhalation exposure
      models are discussed, as well as the research needed to move us forward into this
      exciting new period of development.

PMID- 17505503
TI  - Consumer exposure scenarios: development, challenges and possible solutions.
AB  - Exposure scenarios (ES) under REACH (Registration, Evaluation, and Authorisation
      of Chemicals; new EU legislation) aim to describe safe conditions of product and
      substance use. Both operational conditions and risk management measures (RMMs)
      are part of the ES. For consumer use of chemicals, one of the challenges will be
      to identify all of the consumer uses of a given chemical and then quantify the
      exposure derived from each of them. Product use categories can be established to
      identify in a systematic fashion how products are used. These product categories
      comprise products that are used similarly (e.g. paints, adhesives). They deliver
      information about product use characteristics, and provide an easy-to-handle tool
      for exchanging standardised information. For practical reasons, broad ES will
      have to be developed, which cover a wide range of products and use. The challenge
      will be to define them broadly, but not in a way that they provide such an
      overestimation of exposure that a next iteration or a more complex model is
      always needed. Tiered and targeted approaches for estimation of exposure at the
      right level of detail may offer the best solution. RMMs relevant for consumers
      include those inherent to product design (controllable) and those that are
      communicated to consumers as directions for use (non-controllable).
      Quantification of the effect of non-controllable RMMs on consumer exposure can
      prove to be difficult. REACH requires aggregation of exposure from all relevant
      identified sources. Development of appropriate methodology for realistic
      aggregation of exposure will be no small challenge and will likely require
      probabilistic approaches and comprehensive databases on populations' habits,
      practices and behaviours. REACH regulation aims at controlling the use of
      chemicals so that exposure to every chemical can be demonstrated to be safe for
      consumers, workers, and the environment when considered separately, but also when
      considered in an integrated way. This integration will be another substantial
      challenge for the future.

PMID- 17505504
TI  - A study of health effect estimates using competing methods to model personal
      exposures to ambient PM2.5.
AB  - Various methods have been developed recently to estimate personal exposures to
      ambient particulate matter less than 2.5 microm in diameter (PM2.5) using fixed
      outdoor monitors as well as personal exposure monitors. One class of estimators
      involves extrapolating values using ambient-source components of PM2.5, such as
      sulfate and iron. A key step in extrapolating these values is to correct for
      differences in infiltration characteristics of the component used in
      extrapolation (such as sulfate within PM2.5) and PM2.5. When this is not done,
      resulting health effect estimates will be biased. Another class of approaches
      involves factor analysis methods such as positive matrix factorization (PMF).
      Using either an extrapolation or a factor analysis method in conjunction with
      regression calibration allows one to estimate the direct effects of ambient PM2.5
      on health, eliminating bias caused by using fixed outdoor monitors and estimated
      personal ambient PM2.5 concentrations. Several forms of the extrapolation method
      are defined, including some new ones. Health effect estimates that result from
      the use of these methods are compared with those from an expanded PMF analysis
      using data collected from a health study of asthmatic children conducted in
      Denver, Colorado. Examining differences in health effect estimates among the
      various methods using a measure of lung function (forced expiratory volume in 1
      s) as the health indicator demonstrated the importance of the correction
      factor(s) in the extrapolation methods and that PMF yielded results comparable
      with the extrapolation methods that incorporated correction factors.

PMID- 17505505
TI  - A personal exposure study employing scripted activities and paths in conjunction
      with atmospheric releases of perfluorocarbon tracers in Manhattan, New York.
AB  - A personal exposure study was conducted in New York City as part of the Urban
      Dispersion Program (UDP). It examined the contact of individuals with four
      harmless perflourocarbon tracers (PFT) released in Midtown Manhattan with
      approval by city agencies at separate locations, during two types of experiments,
      completed during each release period. Two continuous 1 h release periods
      separated by a 1.5 h ventilation time were completed on 3 October 2005.
      Stationary site and personal exposure measurements were taken during each period,
      and the first half hour after the release ended. Two types of scripted exposure
      activities are reported: Outdoor Source Scale, and Outdoor Neighborhood Scale;
      requiring 1- and 10-min duration samples, respectively. The results showed that
      exposures were influenced by the surface winds, the urban terrain, and the
      movements of people and vehicles typical in urban centers. The source scale
      exposure data indicated that local conditions significantly affected the
      distribution of each tracer, and consequently the exposures. The highest PFT
      exposures resulted from interaction of the scripted activities with local surface
      conditions. The range measured for 1- min exposures were large with measured
      values exceeding 5000 ppqv (parts per quadrillion by volume). The neighborhood
      scale measurements quantified exposures at distances up to seven blocks away from
      the release points. Generally, but not always, the PFT levels returned quickly to
      zero indicating that after cessation of the emissions the concentrations decrease
      rapidly, and reduce the intensity of local exposures. The near source and
      neighborhood personal exposure route results provided information to establish a
      baseline for determining how a release could affect both the general public and
      emergency responders, and evaluate the adequacy of re-entry or exit strategies
      from a local area. Finally, the data also show that local characteristics can
      produce "hot spots".

PMID- 17505506
TI  - Octreotide and hepatocellular carcinoma.

PMID- 17505507
TI  - Trends in the incidence of adenocarcinoma of the oesophagus and cardia in the
      Netherlands 1989-2003.
AB  - Over the 15-year period 1989-2003, the incidence of oesophagus-cardia
      adenocarcinoma in the Netherlands rose annually by 2.6% for males and 1.2% for
      females. This was the net outcome of annual increases in the incidence of
      adenocarcinoma of the oesophagus (ACO) of 7.2% for males and 3.5% for females and
      annual declines in the incidence of adenocarcinoma of the gastric cardia (AGC) of
      more than 1% for both genders. Nonlinear cohort patterns were found in females
      with ACO and for both genders in AGC; a nonlinear period pattern was observed
      only in males with AGC. These differing epidemiological patterns for ACO and AGC
      do not support a common aetiology. Proposed underlying factors for the rise in
      ACO incidence appear to have little effect on AGC incidence. This and the secular
      decline in smoking among males may have led to the decline in AGC incidence.

PMID- 17505508
TI  - High-grade clear cell renal cell carcinoma has a higher angiogenic activity than
      low-grade renal cell carcinoma based on histomorphological quantification and qRT
      PCR mRNA expression profile.
AB  - Clear cell renal cell carcinoma (CC-RCC) is a highly vascularised tumour and is
      therefore an attractive disease to study angiogenesis and to test novel
      angiogenesis inhibitors in early clinical development. Endothelial cell
      proliferation plays a pivotal role in the process of angiogenesis. The aim of
      this study was to compare angiogenesis parameters in low nuclear grade (n=87) vs
      high nuclear grade CC-RCC (n=63). A panel of antibodies was used for
      immunohistochemistry: CD34/Ki-67, carbonic anhydrase IX, hypoxia-inducible factor
      1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF). Vessel density
      (MVD - microvessel density), endothelial cell proliferation fraction (ECP%) and
      tumour cell proliferation fraction (TCP%) were assessed. mRNA expression levels
      of angiogenesis stimulators and inhibitors were determined by quantitative RT
      PCR. High-grade CC-RCC showed a higher ECP% (P=0.049), a higher TCP% (P=0.009), a
      higher VEGF protein expression (P<0.001), a lower MVD (P< 0.001) and a lower HIF
      1alpha protein expression (P=0.002) than low-grade CC-RCC. Growth factor mRNA
      expression analyses revealed a higher expression of angiopoietin 2 in low-grade
      CC-RCC. Microvessel density and ECP% were inversely correlated (Rho=-0.26,
      P=0.001). Because of the imperfect association of nuclear grade and ECP% or MVD,
      CC-RCC was also grouped based on low/high MVD and ECP%. This analysis revealed a
      higher expression of vessel maturation and stabilisation factors (placental
      growth factor, PDGFB1, angiopoietin 1) in CC-RCC with high MVD, a group of CC-RCC
      highly enriched in low nuclear grade CC-RCC, with low ECP%. Our results suggest
      heterogeneity in angiogenic activity and vessel maturation of CC-RCC, to a large
      extent linked to nuclear grade, and, with probable therapeutic implications.

PMID- 17505509
TI  - Cancer incidence patterns by region and socioeconomic deprivation in teenagers
      and young adults in England.
AB  - Data on 35,291 individuals with cancer, aged 13-24 years, in England from 1979 to
      2001 were analysed by region and socio-economic deprivation of census ward of
      residence, as measured by the Townsend deprivation index. The incidence of
      leukaemia, lymphoma, central nervous system tumours, soft tissue sarcomas,
      gonadal germ cell tumours, melanoma and carcinomas varied by region (P<0.01, all
      groups) but bone tumour incidence did not. Lymphomas, central nervous system
      tumours and gonadal germ cell tumours all had higher incidence in less deprived
      census wards (P<0.01), while chronic myeloid leukaemia and carcinoma of the
      cervix had higher incidence in more deprived wards (P<0.01). In the least
      deprived wards, melanoma incidence was nearly twice that in the most deprived,
      but this trend varied between regions (P<0.001). These cancer incidence patterns
      differ from those seen in both children and older adults and have implications
      for aetiology and prevention.

PMID- 17505510
TI  - CD8+ T cell-mediated control of distant tumours following local photodynamic
      therapy is independent of CD4+ T cells and dependent on natural killer cells.
AB  - Cancer survival rates decrease in the presence of disseminated disease. However,
      there are few therapies that are effective at eliminating the primary tumour
      while providing control of distant stage disease. Photodynamic therapy (PDT) is
      an FDA-approved modality that rapidly eliminates local tumours, resulting in cure
      of early disease and palliation of advanced disease. Numerous pre-clinical
      studies have shown that local PDT treatment of tumours enhances anti-tumour
      immunity. We hypothesised that enhancement of a systemic anti-tumour immune
      response might control the growth of tumours present outside the treatment field.
      To test this hypothesis we delivered PDT to subcutaneous (s.c.) tumours of mice
      bearing both s.c. and lung tumours and monitored the growth of the untreated lung
      tumours. Our results demonstrate that PDT of murine tumours provided durable
      inhibition of the growth of untreated lung tumours. The inhibition of the growth
      of tumours outside the treatment field was tumour-specific and dependent on the
      presence of CD8(+) T cells. This inhibition was accompanied by an increase in
      splenic anti-tumour cytolytic activity and by an increase in CD8(+) T cell
      infiltration into untreated tumours. Local PDT treatment led to enhanced anti
      tumour immune memory that was evident 40 days after tumour treatment and was
      independent of CD4(+) T cells. CD8(+) T cell control of the growth of lung
      tumours present outside the treatment field following PDT was dependent upon the
      presence of natural killer (NK) cells. These results suggest that local PDT
      treatment of tumours lead to induction of an anti-tumour immune response capable
      of controlling the growth of tumours outside the treatment field and indicate
      that this modality has potential in the treatment of distant stage disease.

PMID- 17505511
TI  - Expression of IP-10 related to angiogenesis in uterine cervical cancers.
AB  - Angiogenesis is essential for development, growth and advancement of solid
      tumours. Interferon-gamma-inducible protein 10 (IP-10) regulates lymphocyte
      chemotaxis, mediates vascular pericyte proliferation and acts as an angiostatic
      agent, thus inhibiting tumour growth. This prompted us to study the clinical
      implications of IP-10 expression related to angiogenesis in uterine cervical
      cancers. The levels of IP-10 decreased with advancement, and the prognosis of the
      30 patients with low IP-10 expression in uterine cervical cancers was poor (66%),
      whereas the 24-month survival rate of the other patients with high IP-10
      expression was 90%. Furthermore, IP-10 levels significantly reverse-correlated
      with vascular endothelial growth factor (VEGF) levels in uterine cervical
      cancers. Interferon-gamma-inducible protein 10 might work on suppression of
      angiogenesis associated with VEGF in advancement, and can be recognised as a
      prognostic indicator. Furthermore, IP-10 activation might be effective on the
      suppression of regrowth or recurrence after intensive treatment for advanced
      cervical cancers.

PMID- 17505512
TI  - Investigation of pathogenic mechanisms in multiple colorectal adenoma patients
      without germline APC or MYH/MUTYH mutations.
AB  - Patients with multiple (5-100) colorectal adenomas (MCRAs) often have no germline
      mutation in known predisposition genes, but probably have a genetic origin. We
      collected a set of 25 MCRA patients with no detectable germline mutation in APC,
      MYH/MUTYH or the mismatch repair genes. Extracolonic tumours were absent in these
      cases. No vertical transmission of the MCRA phenotype was found. Based on the
      precedent of MYH-associated polyposis (MAP), we searched for a mutational
      signature in 241 adenomatous polyps from our MCRA cases. Somatic mutation
      frequencies and spectra at APC, K-ras and BRAF were, however, similar to those in
      sporadic colorectal adenomas. Our data suggest that the genetic pathway of
      tumorigenesis in the MCRA patients' tumours is very similar to the classical
      pathway in sporadic adenomas. In sharp contrast to MAP tumours, we did not find
      evidence of a specific mutational signature in any individual patient or in the
      overall set of MCRA cases. These results suggest that hypermutation of APC does
      not cause our patients' disease and strongly suggests that MAP is not a paradigm
      for the remaining MCRA patients. Our MCRA patients' colons showed no evidence of
      microadenomas, unlike in MAP and familial adenomatous polyposis (FAP). However,
      nuclear beta-catenin expression was significantly greater in MCRA patients'
      tumours than in sporadic adenomas. We suggest that, at least in some cases, the
      MCRA phenotype results from germline variation that acts subsequent to tumour
      initiation, perhaps by causing more rapid or more likely progression from
      microadenoma to macroadenoma.

PMID- 17505513
TI  - Mcm2 predicts recurrence hazard in stage Ta/T1 bladder cancer more accurately
      than CK20, Ki67 and histological grade.
AB  - Stage Ta/T1 urothelial carcinoma of the bladder (Ta/T1 BC) has a marked tendency
      to recur. Besides histopathology, markers such as CK20 expression and
      proliferation index (Ki67) have been shown to predict its clinical course. The
      replication-licensing factor minichromosome maintenance protein 2 (Mcm2) is a
      marker of proliferative potential shown to be a promising prognostic marker in
      various malignancies. The aim of the present study was to evaluate the prognostic
      value of Mcm2 in comparison to stage, grade, CK20 and Ki67. Initial sporadic
      Ta/T1 BC (n=71) were evaluated for their expression of CK20, Ki67 and Mcm2 by
      immunohistochemistry and tissue microarray technology. Prognostic power was
      analysed by univariate and multivariate Cox regression model for tumour
      recurrence rate. Median follow-up period was 39 months. A total of 35% patients
      experienced recurrence. While CK20 was not predictive, grade, Ki67 and Mcm2 were
      significantly related to recurrence rate in univariate Cox regression model. Only
      grade (HR 2.37; 95% CI 1.24-4.51; P=0.009) and Mcm2 expression with a cutoff > or
      = 40% (HR 5.81; 95% CI 2.41-14.00; P<0.001) were independent predictors of
      recurrence rate in multivariate Cox regression analysis. In addition to grade,
      expression of Mcm2 is an independent predictor of recurrence in Ta/T1 BC.

PMID- 17505514
TI  - De-regulation of the sonic hedgehog pathway in the InsGas mouse model of gastric
      carcinogenesis.
AB  - This study investigated sonic hedgehog (Shh) signalling in gastric metaplasia in
      the insulin-gastrin (InsGas) hypergastrinaemic mouse +/- Helicobacter felis (H.
      felis) infection. Sonic hedgehog gene and protein expression was reduced in pre
      metaplastic lesions from non-infected mice (90% gene reduction, P<0.01) compared
      to normal mucosa. Sonic hedgehog was reactivated in gastric metaplasia of H.
      felis-infected mice (3.5-fold increase, P<0.01) compared to pre-metaplastic
      lesions. Additionally, the Shh target gene, glioma-associated oncogene (Gli)-1,
      was significantly reduced in the gastric glands of InsGas mice (75% reduction,
      P<0.05) and reactivated with H. felis infection (P<0.05, base of glands, P<0.01
      stroma of metaplastic glands). The ability of H. felis to activate the Shh
      pathway was investigated by measuring the effect of target cytokine, interleukin
      8 (IL-8), on Shh expression in AGS and MGLVA1 cells, which was shown to induce
      Shh expression at physiological concentrations. H. felis induced the expression
      of NF-kappaB in inflammatory infiltrates in vivo, and the expression of the IL-8
      mouse homologue, protein KC, in inflammatory infiltrates and metaplastic lesions.
      Sonic hedgehog pathway reactivation was paralleled with an increase in
      proliferation of metaplastic lesions (15.75 vs 4.39% in infected vs non-infected
      mice, respectively, P<0.001). Furthermore, Shh overexpression increased the
      growth rate of the gastric cancer cell line, AGS. The antiapoptotic protein, bcl
      2, was expressed in the stroma of infected mice, along with a second Shh target
      gene, patched-1 (P=0.0001, stroma of metaplastic gland). This study provides
      evidence suggesting reactivation of Shh signalling from pre-metaplastic to
      advanced metaplastic lesions of the stomach and outlines the importance of the
      Shh pathway as a potential chemoprophylactic target for gastric carcinogenesis.

PMID- 17505515
TI  - Valproic acid inhibits adhesion of vincristine- and cisplatin-resistant
      neuroblastoma tumour cells to endothelium.
AB  - Drug resistance to chemotherapy is often associated with increased malignancy in
      neuroblastoma (NB). In pursuit of alternative treatments for chemoresistant
      tumour cells, we tested the response of multidrug-resistant SKNSH and of
      vincristine (VCR)-, doxorubicin (DOX)-, or cisplatin (CDDP)-resistant UKF-NB-2,
      UKF-NB-3 or UKF-NB-6 NB tumour cell lines to valproic acid (VPA), a
      differentiation inducer currently in clinical trials. Drug resistance caused
      elevated NB adhesion (UKF-NB-2(VCR), UKF-NB-2(DOX), UKF-NB-2(CDDP), UKF-NB
      3(VCR), UKF-NB-3(CDDP), UKF-NB-6(VCR), UKF-NB-6(CDDP)) to an endothelial cell
      monolayer, accompanied by downregulation of the adhesion receptor neural cell
      adhesion molecule (NCAM). Based on the UKF-NB-3 model, N-myc proteins were
      enhanced in UKF-NB-3(VCR) and UKF-NB-3(CDDP), compared to the drug naive
      controls. p73 was diminished, whereas the p73 isoform deltaNp73 was upregulated
      in UKF-NB-3(VCR) and UKF-NB-3(CDDP). Valproic acid blocked adhesion of UKF-NB
      3(VCR) and UKF-NB-3(CDDP), but not of UKF-NB-3(DOX), and induced the upregulation
      of NCAM surface expression, NCAM protein content and NCAM coding mRNA. Valproic
      acid diminished N-myc and enhanced p73 protein level, coupled with downregulation
      of deltaNp73 in UKF-NB-3(VCR) and UKF-NB-3(CDDP). Valproic acid also reverted
      enhanced adhesion properties of drug-resistant UKF-NB-2, UKF-NB-6 and SKNSH
      cells, and therefore may provide an alternative approach to the treatment of drug
      resistant NB by blocking invasive processes.

PMID- 17505516
TI  - Epirubicin-vinorelbine vs FEC100 for node-positive, early breast cancer: French
      Adjuvant Study Group 09 trial.
AB  - The aim of the study was to compare our reference adjuvant chemotherapy, FEC100
      (fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2) and cyclophosphamide 500 mg
      m(-2), six cycles every 21 days), to an epirubicin-vinorelbine (Epi-Vnr)
      combination for early, poor-prognosis breast cancer patients. Patients (482) were
      randomised to receive FEC100, or Epi-Vnr (epirubicin 50 mg m(-2) day 1 and
      vinorelbine 25 mg m(-2), days 1 and 8, six cycles every 21 days). The 7-year
      disease-free survival rates were 59.4 and 58.8%, respectively (P=0.47). The
      relative dose intensity of planned epirubicin doses was 89.1% with FEC100 and
      88.9% with Epi-Vnr. There were significantly more grades 3-4 neutropenia
      (P=0.009) with Epi-Vnr, and significantly more nausea-vomiting (P<0.0001),
      stomatitis (P=0.0007) and alopecia (P<0.0001) with FEC100. No cases of congestive
      heart failure were reported, whereas four decreases in left ventricular ejection
      fraction occurred after FEC100 and five after Epi-Vnr. One case of acute
      myeloblastic leukaemia was registered in the FEC100 arm. After 7 years of follow
      up, there was no difference between treatment arms. Epi-Vnr regimen provided a
      good efficacy in such poor-prognosis breast cancer patients, and could be an
      alternative to FEC100, taking into account respective safety profiles of both
      regimens.

PMID- 17505517
TI  - Characterisation of the anti-apoptotic function of survivin-DeltaEx3 during
      TNFalpha-mediated cell death.
AB  - Survivin is an oncogenic protein involved in cell division and acts as an anti
      apoptotic factor. It is highly expressed in most cancers and is associated with
      chemotherapy resistance, increased tumour recurrence, and shorter patient
      survival. This makes anti-survivin therapy an attractive cancer treatment
      strategy. These functions are mediated by several survivin spliced variants,
      whose expression may correlate with cancer progression. One of the spliced
      variants, survivin-DeltaEx3, is known to inhibit apoptosis, through undefined
      mechanisms. Here, we characterised these mechanisms upon TNFalpha-mediated
      apoptosis, and showed that survivin-DeltaEx3 acts as an adaptor, allowing the
      formation of a complex between Bcl-2 and activated caspase-3. The Bcl-2/survivin
      DeltaEx3 complex, but not survivin-DeltaEx3 itself, inhibits the activity of
      caspase-3. Bcl-2 is therefore linked to the postmitochondrial apoptotic machinery
      by survivin-DeltaEx3. Thus, survivin-DeltaEx3 plays a key role in the inhibition
      of caspase-3 activity, and in the control of the mitochondrial checkpoint of
      apoptosis. This study suggests that targeting survivin-DeltaEx3, rather than
      survivin alone, could be relevant for treating human cancers.

PMID- 17505518
TI  - Agrobacterium ParA/MinD-like VirC1 spatially coordinates early conjugative DNA
      transfer reactions.
AB  - Agrobacterium tumefaciens translocates T-DNA through a polar VirB/D4 type IV
      secretion (T4S) system. VirC1, a factor required for efficient T-DNA transfer,
      bears a deviant Walker A and other sequence motifs characteristic of ParA and
      MinD ATPases. Here, we show that VirC1 promotes conjugative T-DNA transfer by
      stimulating generation of multiple copies per cell of the T-DNA substrate (T
      complex) through pairwise interactions with the processing factors VirD2
      relaxase, VirC2, and VirD1. VirC1 also associates with the polar membrane and
      recruits T-complexes to cell poles, the site of VirB/D4 T4S machine assembly.
      VirC1 Walker A mutations abrogate T-complex generation and polar recruitment,
      whereas the native protein recruits T-complexes to cell poles independently of
      other polar processing factors (VirC2, VirD1) or T4S components (VirD4 substrate
      receptor, VirB channel subunits). We propose that A. tumefaciens has appropriated
      a progenitor ParA/MinD-like ATPase to promote conjugative DNA transfer by: (i)
      nucleating relaxosome assembly at oriT-like T-DNA border sequences and (ii)
      spatially positioning the transfer intermediate at the cell pole to coordinate
      substrate-T4S channel docking.

PMID- 17505520
TI  - Centrosome biogenesis and function: centrosomics brings new understanding.
AB  - Centrosomes, which were first described in the late 19th century, are found in
      most animal cells and undergo duplication once every cell cycle so that their
      number remains stable, like the genetic material of a cell. However, their
      function and regulation have remained elusive and controversial. Only recently
      has some understanding of these fundamental aspects of centrosome function and
      biogenesis been gained through the concerted application of genomics and
      proteomics, which we term 'centrosomics'. The identification of new molecules has
      highlighted the evolutionary conservation of centrosome function and provided a
      conceptual framework for understanding centrosome behaviour and how it can go
      awry in human disease.

PMID- 17505521
TI  - Inheritance and biogenesis of organelles in the secretory pathway.
AB  - In eukaryotic cells, cellular functions are compartmentalized into membrane-bound
      organelles. This has many advantages, as shown by the success of the eukaryotic
      lineage, but creates many problems for cells, such as the need to build and
      partition these organelles during cell growth and division. Diverse mechanisms
      for biogenesis of the endoplasmic reticulum and Golgi apparatus have evolved,
      ranging from de novo synthesis to the copying of a template organelle. The
      different mechanisms by which organelles are inherited in yeasts, protozoa and
      metazoans probably reflect the differences in the structure and copy number of
      these organelles.

PMID- 17505522
TI  - Harnessing calcineurin as a novel anti-infective agent against invasive fungal
      infections.
AB  - The number of immunocompromised patients with invasive fungal infections
      continues to increase and new antifungal therapies are not keeping pace with the
      growing incidence of these infections and their associated mortality. Calcineurin
      inhibition is currently used to exert effective immunosuppression following organ
      transplantation and in treating various other conditions. However, the
      calcineurin pathway is also intricately involved in the growth and pathogenesis
      of the three major fungal pathogens of humans, Cryptococcus neoformans, Candida
      albicans and Aspergillus fumigatus, and the exploitation of fungal calcineurin
      pathways holds great promise for the future development of novel antifungal
      agents. This Review summarizes our current understanding of calcineurin biology
      in these fungal species, and its exciting potential role in treating invasive
      fungal infections.

PMID- 17505523
TI  - Mechanosensitive channels in bacteria: signs of closure?
AB  - Bacterial mechanosensitive channels are activated by increases in tension in the
      lipid bilayer of the cytoplasmic membrane, where they transiently create large
      pores in a controlled manner. Mechanosensitive channel research has benefited
      from advances in electrophysiology, genomics and molecular genetics as well as
      from the application of biophysical techniques. Most recently, new analytical
      methods have been used to complement existing knowledge and generate insights
      into the molecular interactions that take place between mechanosensitive channel
      proteins and the surrounding membrane lipids. This article reviews the latest
      developments.

PMID- 17505524
TI  - Helicobacter pylori evolution and phenotypic diversification in a changing host.
AB  - Helicobacter pylori colonizes the stomachs of more than 50% of the world's
      population, making it one of the most successful of all human pathogens. One
      striking characteristic of H. pylori biology is its remarkable allelic diversity
      and genetic variability. Not only does almost every infected person harbour their
      own individual H. pylori strain, but strains can undergo genetic alteration in
      vivo, driven by an elevated mutation rate and frequent intraspecific
      recombination. This genetic variability, which affects both housekeeping and
      virulence genes, has long been thought to contribute to host adaptation, and
      several recently published studies support this concept. We review the available
      knowledge relating to the genetic variation of H. pylori, with special emphasis
      on the changes that occur during chronic colonization, and argue that H. pylori
      uses mutation and recombination processes to adapt to its individual host by
      modifying molecules that interact with the host. Finally, we put forward the
      hypothesis that the lack of opportunity for intraspecies recombination as a
      result of the decreasing prevalence of H. pylori could accelerate its
      disappearance from Western populations.

PMID- 17505525
TI  - Fanconi anemia: Fanconi anemia, breast and embryonal cancer risk revisited.

PMID- 17505526
TI  - Vascular pathologies. Angiogenomics: towards a genetic nosology and understanding
      of vascular anomalies.

PMID- 17505527
TI  - ALOX5AP gene variants and risk of coronary artery disease: an angiography-based
      study.
AB  - The aim of this study was to explore the role of variants of the gene encoding
      arachidonate 5-lipoxygenase-activating protein (ALOX5AP) as possible
      susceptibility factors for coronary artery disease (CAD) and myocardial
      infarction (MI) in patients with or without angiographically proven CAD. A total
      of 1431 patients with or without angiographically documented CAD were examined
      simultaneously for seven ALOX5AP single-nucleotide polymorphisms, allowing
      reconstruction of the at-risk haplotypes (HapA and HapB) previously identified in
      the Icelandic and British populations. Using a haplotype-based approach, HapA was
      not associated with either CAD or MI. On the other hand, HapB and another
      haplotype within the same region (that we named HapC) were significantly more
      represented in CAD versus CAD-free patients, and these associations remained
      significant after adjustment for traditional cardiovascular risk factors by
      logistic regression (HapB: odds ratio (OR) 1.67, 95% confidence interval (CI)
      1.04-2.67; P=0.032; HapC: OR 2.41, 95% CI 1.09-5.32; P=0.030). No difference in
      haplotype distributions was observed between CAD subjects with or without a
      previously documented MI. Our angiography-based study suggests a possible modest
      role of ALOX5AP in the development of the atheroma rather than in its late
      thrombotic complications such as MI.

PMID- 17505529
TI  - Grade migration in prostate cancer: an analysis using the Surveillance,
      Epidemiology, and End Results registry.
AB  - To utilize the Surveillance, Epidemiology, and End Results (SEER) registry to
      examine trends in grade assignment. Data from 411 325 patients from 1984 to 2003
      were analyzed for grade migration and for cause-specific survival (CSS) as a
      function of grade. There has been a significant grade migration during the study
      period (P<0.001), principally from well-differentiated (WD) to moderately
      differentiated (MD) disease. Five-year CSS of MD and WD patients have converged,
      suggesting a decreasing role of grade as a prognostic factor. A grade migration
      from WD to MD assignment has occurred, suggesting that prognostic categorizations
      based on grade across eras may be difficult to interpret.

PMID- 17505528
TI  - Transcriptional regulation of TLX2 and impaired intestinal innervation: possible
      role of the PHOX2A and PHOX2B genes.
AB  - TLX2 (also known as HOX11L1, Ncx and Enx) is a transcription factor playing a
      crucial role in the development of the enteric nervous system, as confirmed by
      mice models exhibiting intestinal hyperganglionosis and pseudo-obstruction.
      However, congenital defects of TLX2 have been excluded as a major cause of
      intestinal motility disorders in patients affected with intestinal neuronal
      dysplasia (IND) or pseudo-obstruction. After demonstrating the direct regulation
      of TLX2 expression by the homeoprotein PHOX2B, in the present work, we have
      focused on its paralogue PHOX2A. By co-transfections, electrophoretic mobility
      shift assays and chromatin immunoprecipitation, we have demonstrated that PHOX2A,
      like PHOX2B, is involved in the cascade leading to TLX2 transactivation and
      presumably in the intestinal neuronal differentiation. Based on the hypothesis
      that missed activation of the TLX2 gene induces the development of enteric
      nervous system defects, PHOX2A and PHOX2B have been regarded as novel candidate
      genes involved in IND and pseudo-obstruction and consequently analyzed for
      mutations in a specific set of 26 patients. We have identified one still
      unreported PHOX2A variant; however, absence of any functional effect on TLX2
      transactivation suggests that regulators or effectors other than the PHOX2 genes
      must act in the same pathway, likely playing a non redundant and direct role in
      the pathogenesis of such enteric disorders.

PMID- 17505530
TI  - Spectroscopic, thermal and biological studies on some trivalent ruthenium and
      rhodium NS chelating thiosemicarbazone complexes.
AB  - The synthetic, spectroscopic, and biological studies of sixteen ring-substituted
      4-phenylthiosemicarbazones and 4-nitrophenyl-thiosemicarbazones of anisaldehyde,
      4-chlorobenzaldehyde, 4-fluorobenzaldehyde, and vanillin with ruthenium(III) and
      rhodium(III) chlorides are reported here. Their structures were determined on the
      basis of the elemental analyses, spectroscopic data (IR, electronic, (1)H and
      (13)C NMR) along with magnetic susceptibility measurements, molar conductivity
      and thermogravimetric analyses. Electrical conductance measurement revealed a 1 :
      3 electrolytic nature of the complexes. The resulting colored products are
      monomeric in nature. On the basis of the above studies, three ligands were
      suggested to be coordinated to each metal atom by thione sulphur and azomethine
      nitrogen to form low-spin octahedral complexes with ruthenium(III) while forming
      diamagnetic complexes with rhodium(III). Both ligands and their complexes have
      been screened for their bactericidal activities and the results indicate that
      they exhibit a significant activity.

PMID- 17505531
TI  - Application of vacuum-assisted therapy in postoperative ascitic fluid leaks: an
      integral part of multimodality wound management in cirrhotic patients.
AB  - Surgery in patients with hepatic cirrhosis and ascites is associated with
      significant morbidity, including poor wound healing. Postoperative management of
      abdominal and perineal wounds in these patients poses a unique challenge owing to
      increased intra-abdominal pressure, risk for peritonitis, and ascitic fluid
      leakage. Vacuum-assisted closure (VAC) therapy reportedly improves angiogenesis
      and epithelialization, controls bacterial contamination, and removes excess
      tissue fluid. We present 4 cases of successful management of intractable
      postoperative ascitic fluid leaks utilizing VAC-based techniques. In one case,
      closure of a profusely draining perineal wound following an abdominoperineal
      resection was accomplished within 5 days of specialized VAC dressing application.
      In the other 3 cases, refractory drainage from midline laparotomy incision was
      successfully managed with the use of VAC therapy. In all 4 cases, the VAC-based
      system was effective in controlling drainage of ascites and subsequently sealing
      the wounds. Postoperative use of VAC in conjunction with optimization of medical
      therapy and judicious tapping of ascites provides a safe and effective method to
      control ascitic fluid leaks and promote definitive tissue sealing in patients
      with hepatic cirrhosis.

PMID- 17505532
TI  - Evidence that p53-mediated cell-cycle-arrest inhibits chemotherapeutic treatment
      of ovarian carcinomas.
AB  - Gene expression profiles of malignant tumors surgically removed from ovarian
      cancer patients pre-treated with chemotherapy (neo-adjuvant) prior to surgery
      group into two distinct clusters. One group clusters with carcinomas from
      patients not pre-treated with chemotherapy prior to surgery (C-L), while the
      other clusters with non-malignant adenomas (A-L). We show here that although the
      C-L cluster is preferentially associated with p53 loss-of-function (LOF)
      mutations, the C-L cluster cancer patients display a more favorable clinical
      response to chemotherapy as evidenced by enhanced long-term survivorships. Our
      results support a model whereby p53 mediated cell-cycle-arrest/DNA repair serves
      as a barrier to optimal chemotherapeutic treatment of ovarian and perhaps other
      carcinomas and suggest that inhibition of p53 during chemotherapy may enhance
      clinical outcome.

PMID- 17505533
TI  - Comparative population genetics of the immunity gene, Relish: is adaptive
      evolution idiosyncratic?
AB  - The frequency of adaptive evolution acting on common loci in distant lineages
      remains an outstanding question in evolutionary biology. We asked whether the
      immunity factor, Relish, a gene with a history of directional selection in
      Drosophila simulans, shows evidence of a similar selective history in other
      Drosophila species. We found only weak evidence of recurrent adaptive protein
      evolution at the Relish locus in three sister species pairs, suggesting that this
      key component of the insect immune system has an idiosyncratic evolutionary
      history in Drosophila.

PMID- 17505535
TI  - Economic inequality predicts biodiversity loss.
AB  - Human activity is causing high rates of biodiversity loss. Yet, surprisingly
      little is known about the extent to which socioeconomic factors exacerbate or
      ameliorate our impacts on biological diversity. One such factor, economic
      inequality, has been shown to affect public health, and has been linked to
      environmental problems in general. We tested how strongly economic inequality is
      related to biodiversity loss in particular. We found that among countries, and
      among US states, the number of species that are threatened or declining increases
      substantially with the Gini ratio of income inequality. At both levels of
      analysis, the connection between income inequality and biodiversity loss persists
      after controlling for biophysical conditions, human population size, and per
      capita GDP or income. Future research should explore potential mechanisms behind
      this equality-biodiversity relationship. Our results suggest that economic
      reforms would go hand in hand with, if not serving as a prerequisite for,
      effective conservation.

PMID- 17505534
TI  - LRP1 functions as an atheroprotective integrator of TGFbeta and PDFG signals in
      the vascular wall: implications for Marfan syndrome.
AB  - BACKGROUND: The multifunctional receptor LRP1 controls expression, activity and
      trafficking of the PDGF receptor-beta in vascular smooth muscle cells (VSMC).
      LRP1 is also a receptor for TGFbeta1 and is required for TGFbeta mediated
      inhibition of cell proliferation. METHODS AND PRINCIPAL FINDINGS: We show that
      loss of LRP1 in VSMC (smLRP(-)) in vivo results in a Marfan-like syndrome with
      nuclear accumulation of phosphorylated Smad2/3, disruption of elastic layers,
      tortuous aorta, and increased expression of the TGFbeta target genes
      thrombospondin-1 (TSP1) and PDGFRbeta in the vascular wall. Treatment of smLRP1(
      ) animals with the PPARgamma agonist rosiglitazone abolished nuclear pSmad
      accumulation, reversed the Marfan-like phenotype, and markedly reduced smooth
      muscle proliferation, fibrosis and atherosclerosis independent of plasma
      cholesterol levels. CONCLUSIONS AND SIGNIFICANCE: Our findings are consistent
      with an activation of TGFbeta signals in the LRP1-deficient vascular wall. LRP1
      may function as an integrator of proliferative and anti-proliferative signals
      that control physiological mechanisms common to the pathogenesis of Marfan
      syndrome and atherosclerosis, and this is essential for maintaining vascular wall
      integrity.

PMID- 17505536
TI  - Effects of BRCA1 transgene expression on murine mammary gland development and
      mutagen-induced mammary neoplasia.
AB  - To characterize the role of BRCA1 in mammary gland development and tumor
      suppression, a transgenic mouse model of BRCA1 overexpression was developed.
      Using the mouse mammary tumor virus (MMTV) promoter/enhancer, transgenic mice
      expressing human BRCA1 or select mutant controls were generated. Transgenic
      animals examined during adolescence were shown to express the human transgene in
      their mammary glands. The mammary glands of 13-week-old virgin homozygous MMTV
      BRCA1 mice presented the morphology of moderately increased lobulo-alveolar
      development. The mammary ductal trees of both hemizygous and homozygous MMTV
      BRCA1t340 were similar to those of control non-transgenic littermates.
      Interestingly, both hemi- and homozygous mice expressing a splice variant of
      BRCA1 lacking the N-terminal RING finger domain (MMTV-BRCA1sv) exhibited marked
      mammary lobulo-alveolar development, particularly terminal end bud proliferation.
      Morphometric analyses of mammary gland whole mount preparations were used to
      measure epithelial staining indices of ~35% for homozygous MMTV-BRCA1 mice and
      ~60% for both hemizygous and homozygous MMTV-BRCA1sv mice versus ~25% for non
      transgenic mice. Homozygous MMTV-BRCA1 mice showed delayed development of tumors
      when challenged with 7,12 dimethylbenzanthracene (DMBA), relative to non
      transgenic and homozygous BRCA1t340 expressing mice. In contrast, homozygous MMTV
      BRCA1sv transgenic animals were sensitized to DMBA treatment and exhibited a very
      rapid onset of mammary tumor development and accelerated mortality. MMTV-BRCA1
      effects on mortality were restricted to DMBA-induced tumors of the mammary gland.
      These results demonstrate in vivo roles for BRCA1 in both mammary gland
      development and in tumor suppression against mutagen-induced mammary gland
      neoplasia.

PMID- 17505537
TI  - Development of a highly sensitive and selective microplate chemiluminescence
      enzyme immunoassay for the determination of free thyroxine in human serum.
AB  - A microplate chemiluminescence enzyme immunoassay (CLEIA) with high sensitivity,
      selectivity and reproducibility was developed for the determination of free
      thyroxine (FT4) in human serum. A competitive assay has been utilized with
      horseradish peroxidase (HRP) labeled thyroxine analog in the chemiluminescence
      (CL) detection. The CL signal produced by the emission of photons from luminol
      was directly proportional to the amount of analyte. The linear range was 0.45-7.5
      ng dL(-1 )and the detection limit was 0.09 ng dL(-1). Experimental conditions,
      such as temperature, pH, incubation time, titration level and other relevant
      variables upon the CL signal have been examined and optimized. A coefficient of
      variance of less than 16% was obtained for intra- and inter-assay precision. The
      present method has been successfully applied to the analysis of FT4 in human
      serum. The positive and negative coincidence ratios are satisfactory. Good
      correlations were obtained between the results by the proposed method and
      radioimmunoassay (RIA), as well as a Bayer ACS-180SE detection system.

PMID- 17505538
TI  - Human Maf1 negatively regulates RNA polymerase III transcription via the TFIIB
      family members Brf1 and Brf2.
AB  - RNA polymerase III (RNA pol III) transcribes many of the small structural RNA
      molecules involved in processing and translation, thereby regulating the growth
      rate of a cell. Initiation of pol III transcription requires the evolutionarily
      conserved pol III initiation factor TFIIIB. TFIIIB is the molecular target of
      regulation by tumor suppressors, including p53, RB and the RB-related pocket
      proteins. However, our understanding of negative regulation of human TFIIIB
      mediated transcription by other proteins is limited. In this study we
      characterize a RNA pol III luciferase assay and further demonstrate in vivo that
      a human homolog of yeast Maf1 represses RNA pol III transcription. Additionally,
      we show that Maf1 repression of RNA pol III transcription occurs via TFIIIB,
      specifically through the TFIIB family members Brf1 and Brf2.

PMID- 17505539
TI  - Proteomics analysis of the expression of neurogranin in murine neuroblastoma
      (Neuro-2a) cells reveals its involvement for cell differentiation.
AB  - Neurogranin (Ng) is a neural-specific, calmodulin (CaM)-binding protein that is
      phosphorylated by protein kinase C (PKC). Although its biochemical property has
      been well characterized, the physiological function of Ng needs to be elucidated.
      In the present study, we performed proteomics analysis of the induced
      compositional changes due to the expression of Ng in murine neuroblastoma (Neuro
      2a) cells using isotope coded affinity tags (ICAT) combined with 2-dimensional
      liquid chromatography/tandem mass spectrometry (2D-LC/MS/MS). We found that 40%
      of identified proteins were down-regulated and most of these proteins are
      microtubule components and associated proteins that mediated neurite outgrowth.
      Western blot experiments confirmed the expression of alpha-tubulin and
      microtubule- associated protein 1B (MAP 1B) was dramatically reduced in Neuro-2a
      Ng cells compared to control. Cell morphology of Neuro-2a-Ng showed far less
      neurites than the control. Serum deprivation induced the extension of only one or
      two long neurites per cell in Neuro-2a-Ng, contrasting to the extension of
      multiple neurites per control cell. Ng may be linked to neurite formation by
      affecting expression of several microtubule related proteins. Furthermore, the
      PKC activator (PMA) induced an enhanced ERK1/2 activity in the cells that
      expressed Ng. The mutation of Ng at S36A caused sustained increase of ERK1/2
      activity, whereas the ERK1/2 activity in mutation at I33Q showed no difference
      compared to wild type Ng, suggesting the phosphorylation of Ng but not the CaM
      /Ng interaction plays an important role in ERK activation. Ng may be involved in
      neuronal growth and differentiation via PKC and ERK1/2 signaling pathways.

PMID- 17505540
TI  - Calculation of the free energy and cooperativity of protein folding.
AB  - Calculation of the free energy of protein folding and delineation of its pre
      organization are of foremost importance for understanding, predicting and
      designing biological macromolecules. Here, we introduce an energy smoothing
      variant of parallel tempering replica exchange Monte Carlo (REMS) that allows for
      efficient configurational sampling of flexible solutes under the conditions of
      molecular hydration. Its usage to calculate the thermal stability of a model
      globular protein, Trp cage TC5b, achieves excellent agreement with experimental
      measurements. We find that the stability of TC5b is attained through the coupled
      formation of local and non-local interactions. Remarkably, many of these
      structures persist at high temperature, concomitant with the origin of native
      like configurations and mesostates in an otherwise macroscopically disordered
      unfolded state. Graph manifold learning reveals that the conversion of these
      mesostates to the native state is structurally heterogeneous, and that the
      cooperativity of their formation is encoded largely by the unfolded state
      ensemble. In all, these studies establish the extent of thermodynamic and
      structural pre-organization of folding of this model globular protein, and
      achieve the calculation of macromolecular stability ab initio, as required for ab
      initio structure prediction, genome annotation, and drug design.

PMID- 17505541
TI  - A model of late long-term potentiation simulates aspects of memory maintenance.
AB  - Late long-term potentiation (L-LTP) denotes long-lasting strengthening of
      synapses between neurons. L-LTP appears essential for the formation of long-term
      memory, with memories at least partly encoded by patterns of strengthened
      synapses. How memories are preserved for months or years, despite molecular
      turnover, is not well understood. Ongoing recurrent neuronal activity, during
      memory recall or during sleep, has been hypothesized to preferentially potentiate
      strong synapses, preserving memories. This hypothesis has not been evaluated in
      the context of a mathematical model representing ongoing activity and biochemical
      pathways important for L-LTP. In this study, ongoing activity was incorporated
      into two such models - a reduced model that represents some of the essential
      biochemical processes, and a more detailed published model. The reduced model
      represents synaptic tagging and gene induction simply and intuitively, and the
      detailed model adds activation of essential kinases by Ca(2+). Ongoing activity
      was modeled as continual brief elevations of Ca(2+). In each model, two stable
      states of synaptic strength/weight resulted. Positive feedback between synaptic
      weight and the amplitude of ongoing Ca(2+) transients underlies this bistability.
      A tetanic or theta-burst stimulus switches a model synapse from a low basal
      weight to a high weight that is stabilized by ongoing activity. Bistability was
      robust to parameter variations in both models. Simulations illustrated that
      prolonged periods of decreased activity reset synaptic strengths to low values,
      suggesting a plausible forgetting mechanism. However, episodic activity with
      shorter inactive intervals maintained strong synapses. Both models support
      experimental predictions. Tests of these predictions are expected to further
      understanding of how neuronal activity is coupled to maintenance of synaptic
      strength. Further investigations that examine the dynamics of activity and
      synaptic maintenance can be expected to help in understanding how memories are
      preserved for up to a lifetime in animals including humans.

PMID- 17505543
TI  - Conditional expression of Wnt4 during chondrogenesis leads to dwarfism in mice.
AB  - Wnts are expressed in the forming long bones, suggesting roles in skeletogenesis.
      To examine the action of Wnts in skeleton formation, we developed a genetic
      system to conditionally express Wnt4 in chondrogenic tissues of the mouse. A
      mouse Wnt4 cDNA was introduced into the ubiquitously expressed Rosa26 (R26) locus
      by gene targeting in embryonic stem (ES) cells. The expression of Wnt4 from the
      R26 locus was blocked by a neomycin selection cassette flanked by loxP sites
      (floxneo) that was positioned between the Rosa26 promoter and the Wnt4 cDNA,
      creating the allele designated R26(floxneoWnt4). Wnt4 expression was activated
      during chondrogenesis using Col2a1-Cre transgenic mice that express Cre
      recombinase in differentiating chondrocytes. R26(floxneoWnt4); Col2a1-Cre double
      heterozygous mice exhibited a growth deficiency, beginning approximately 7 to 10
      days after birth, that resulted in dwarfism. In addition, they also had
      craniofacial abnormalities, and delayed ossification of the lumbar vertebrae and
      pelvic bones. Histological analysis revealed a disruption in the organization of
      the growth plates and a delay in the onset of the primary and secondary
      ossification centers. Molecular studies showed that Wnt4 overexpression caused
      decreased proliferation and altered maturation of chondrocytes. In addition,
      R26(floxneoWnt4); Col2a1-Cre mice had decreased expression of vascular
      endothelial growth factor (VEGF). These studies demonstrate that Wnt4
      overexpression leads to dwarfism in mice. The data indicate that Wnt4 levels must
      be regulated in chondrocytes for normal growth plate development and
      skeletogenesis. Decreased VEGF expression suggests that defects in
      vascularization may contribute to the dwarf phenotype.

PMID- 17505542
TI  - Order in spontaneous behavior.
AB  - Brains are usually described as input/output systems: they transform sensory
      input into motor output. However, the motor output of brains (behavior) is
      notoriously variable, even under identical sensory conditions. The question of
      whether this behavioral variability merely reflects residual deviations due to
      extrinsic random noise in such otherwise deterministic systems or an intrinsic,
      adaptive indeterminacy trait is central for the basic understanding of brain
      function. Instead of random noise, we find a fractal order (resembling Levy
      flights) in the temporal structure of spontaneous flight maneuvers in tethered
      Drosophila fruit flies. Levy-like probabilistic behavior patterns are
      evolutionarily conserved, suggesting a general neural mechanism underlying
      spontaneous behavior. Drosophila can produce these patterns endogenously, without
      any external cues. The fly's behavior is controlled by brain circuits which
      operate as a nonlinear system with unstable dynamics far from equilibrium. These
      findings suggest that both general models of brain function and autonomous agents
      ought to include biologically relevant nonlinear, endogenous behavior-initiating
      mechanisms if they strive to realistically simulate biological brains or out
      compete other agents.

PMID- 17505544
TI  - Immunity against Ixodes scapularis salivary proteins expressed within 24 hours of
      attachment thwarts tick feeding and impairs Borrelia transmission.
AB  - In North America, the black-legged tick, Ixodes scapularis, an obligate
      haematophagus arthropod, is a vector of several human pathogens including
      Borrelia burgdorferi, the Lyme disease agent. In this report, we show that the
      tick salivary gland transcriptome and proteome is dynamic and changes during the
      process of engorgement. We demonstrate, using a guinea pig model of I. scapularis
      feeding and B. burgdorferi transmission, that immunity directed against salivary
      proteins expressed in the first 24 h of tick attachment - and not later - is
      sufficient to evoke all the hallmarks of acquired tick-immunity, to thwart tick
      feeding and also to impair Borrelia transmission. Defining this subset of
      proteins will promote a mechanistic understanding of novel I. scapularis proteins
      critical for the initiation of tick feeding and for Borrelia transmission.

PMID- 17505545
TI  - Screen for genetic modifiers of stbm reveals that photoreceptor fate and rotation
      can be genetically uncoupled in the Drosophila eye.
AB  - BACKGROUND: Polarity of the Drosophila compound eye arises primarily as a
      consequence of two events that are tightly linked in time and space: fate
      specification of two photoreceptor cells, R3 and R4, and the subsequent
      directional movement of the unit eyes of the compound eye, or ommatidia. While it
      is thought that these fates dictate the direction of ommatidial rotation, the
      phenotype of mutants in the genes that set up this polarity led to the hypothesis
      that these two events could be uncoupled. METHODOLOGY/PRINCIPAL FINDINGS: To
      definitively demonstrate these events are genetically separable, we conducted a
      dominant modifier screen to determine if genes, when misexpressed, could
      selectively enhance subclasses of mutant ommatidia in which the direction of
      rotation does not follow the R3/R4 cell fates, yet not affect the number of
      ommatidia in which rotation follows the R3/R4 cell fates. We identified a subset
      of P element lines that exhibit this selective enhancement. We also identified
      lines that behave in the opposite manner: They enhance the number of ommatidia
      that rotate in the right direction, but do not alter the number of ommatidia that
      rotate incorrectly with respect to the R3/R4 fates. CONCLUSIONS/SIGNIFICANCE:
      These results indicate that fate and direction of rotation can be genetically
      separated, and that there are genes that act between R3/R4 fate specification and
      direction of ommatidial rotation. These data affirm what has been a long-standing
      assumption about the genetic control of ommatidial polarity.

PMID- 17505546
TI  - Changing human visual field organization from early visual to extra-occipital
      cortex.
AB  - BACKGROUND: The early visual areas have a clear topographic organization, such
      that adjacent parts of the cortical surface represent distinct yet adjacent parts
      of the contralateral visual field. We examined whether cortical regions outside
      occipital cortex show a similar organization. METHODOLOGY/PRINCIPAL FINDINGS: The
      BOLD responses to discrete visual field locations that varied in both polar angle
      and eccentricity were measured using two different tasks. As described
      previously, numerous occipital regions are both selective for the contralateral
      visual field and show topographic organization within that field. Extra-occipital
      regions are also selective for the contralateral visual field, but possess little
      (or no) topographic organization. A regional analysis demonstrates that this weak
      topography is not due to increased receptive field size in extra-occipital areas.
      CONCLUSIONS/SIGNIFICANCE: A number of extra-occipital areas are identified that
      are sensitive to visual field location. Neurons in these areas corresponding to
      different locations in the contralateral visual field do not demonstrate any
      regular or robust topographic organization, but appear instead to be intermixed
      on the cortical surface. This suggests a shift from processing that is
      predominately local in visual space, in occipital areas, to global, in extra
      occipital areas. Global processing fits with a role for these extra-occipital
      areas in selecting a spatial locus for attention and/or eye-movements.

PMID- 17505548
TI  - When should we pay attention to unfavorable news from pregnancy registries?

PMID- 17505547
TI  - Genetic evidence for a link between glycolysis and DNA replication.
AB  - BACKGROUND: A challenging goal in biology is to understand how the principal
      cellular functions are integrated so that cells achieve viability and optimal
      fitness in a wide range of nutritional conditions. METHODOLOGY/PRINCIPAL
      FINDINGS: We report here a tight link between glycolysis and DNA synthesis. The
      link, discovered during an analysis of suppressors of thermosensitive replication
      mutants in bacterium Bacillus subtilis, is very strong as some metabolic
      alterations fully restore viability to replication mutants in which a lethal
      arrest of DNA synthesis otherwise occurs at a high, restrictive, temperature.
      Full restoration of viability by such alterations was limited to cells with
      mutations in three elongation factors (the lagging strand DnaE polymerase, the
      primase and the helicase) out of a large set of thermosensitive mutants affected
      in most of the replication proteins. Restoration of viability resulted, at least
      in part, from maintenance of replication protein activity at high temperature.
      Physiological studies suggested that this restoration depended on the activity of
      the three-carbon part of the glycolysis/gluconeogenesis pathway and occurred in
      both glycolytic and gluconeogenic regimens. Restoration took place abruptly over
      a narrow range of expression of genes in the three-carbon part of glycolysis.
      However, the absolute value of this range varied greatly with the allele in
      question. Finally, restoration of cell viability did not appear to be the result
      of a decrease in growth rate or an induction of major stress responses.
      CONCLUSIONS/SIGNIFICANCE: Our findings provide the first evidence for a genetic
      system that connects DNA chain elongation to glycolysis. Its role may be to
      modulate some aspect of DNA synthesis in response to the energy provided by the
      environment and the underlying mechanism is discussed. It is proposed that
      related systems are ubiquitous.

PMID- 17505549
TI  - It's about time: long-term memory outcome following temporal lobectomy.

PMID- 17505550
TI  - Vaccines, encephalopathies, and mutations.

PMID- 17505551
TI  - Revisiting the well-established subject of stroke and epilepsy.

PMID- 17505552
TI  - New roles for interleukin-1 Beta in the mechanisms of epilepsy.
AB  - The mechanisms that transform a normal brain to an epileptic one are not fully
      understood. Interleukin-1 beta (IL-1beta) contributes to neuronal degeneration
      observed in several neurological disorders and recently has been implicated in
      neuronal injury that may accompany the process of epileptogenesis. This review
      presents the hypothesis that IL-1beta may contribute to the development of
      epilepsy via several mechanisms, including classical effects on neuronal survival
      and transcription pathways; novel rapid effects on receptor-gated ion channels;
      and long-lasting effects on expression of selective gene families. Thus, evidence
      that IL-1beta actions in epilepsy can be independent from the neurotoxic effects
      of this cytokine is presented.

PMID- 17505553
TI  - Means, motive, and opportunity: establishing culpability in pharmacoresistant
      epilepsy.

PMID- 17505554
TI  - A possible explanation for the paradox of hyperexcitability and epilepsy in "loss
      of function" voltage-gated sodium channel mutations.

PMID- 17505555
TI  - Brain water and ion fluxes: a hard-to-die hypothesis to explain seizures.

PMID- 17505556
TI  - The ketogenic diet: stoking the powerhouse of the cell.

PMID- 17505557
TI  - Advances in the radiosurgical treatment of epilepsy.
AB  - Radiosurgery is the precise application of focused radiation to a targeted volume
      area within the brain, which has been identified on MRI. With recent advances,
      radiosurgical treatment is now being evaluated as an alternative treatment to
      open resective surgery for intractable epilepsy. Recent prospective trials
      suggest that radiosurgery may be an effective and safe treatment for medically
      intractable epilepsy associated with mesial temporal sclerosis, cavernous
      malformations, and hypothalamic hamartomas.

PMID- 17505558
TI  - Thioglycosides as inhibitors of hSGLT1 and hSGLT2: potential therapeutic agents
      for the control of hyperglycemia in diabetes.
AB  - The treatment of diabetes has been mainly focused on maintaining normal blood
      glucose concentrations. Insulin and hypoglycemic agents have been used as
      standard therapeutic strategies. However, these are characterized by limited
      efficacy and adverse side effects, making the development of new therapeutic
      alternatives mandatory. Inhibition of glucose reabsorption in the kidney,
      mediated by SGLT1 or SGLT2, represents a promising therapeutic approach.
      Therefore, the aim of the present study was to evaluate the effect of
      thioglycosides on human SGLT1 and SGLT2. For this purpose, stably transfected
      Chinese hamster ovary (CHO) cells expressing human SGLT1 and SGLT2 were used. The
      inhibitory effect of thioglycosides was assessed in transport studies and
      membrane potential measurements, using alpha-methyl-glucoside uptake and
      fluorescence resonance energy transfer, respectively. We found that some
      thioglycosides inhibited hSGLT more strongly than phlorizin. Specifically,
      thioglycoside I (phenyl-1'-thio-beta-D-glucopyranoside) inhibited hSGLT2 stronger
      than hSGLT1 and to a larger extent than phlorizin. Thioglycoside VII (2
      hydroxymethyl-phenyl-1'-thio-beta-D-galacto-pyranoside) had a pronounced
      inhibitory effect on hSGLT1 but not on hSGLT2. Kinetic studies confirmed the
      inhibitory effect of these thioglycosides on hSGLT1 or hSGLT2, demonstrating
      competitive inhibition as the mechanism of action. Therefore, these
      thioglycosides represent promising therapeutic agents for the control of
      hyperglycemia in patients with diabetes.

PMID- 17505559
TI  - BRCA1 may modulate neuronal cell cycle re-entry in Alzheimer disease.
AB  - In Alzheimer disease, neuronal degeneration and the presence of neurofibrillary
      tangles correlate with the severity of cognitive decline. Neurofibrillary tangles
      contain the antigenic profile of many cell cycle markers, reflecting a re-entry
      into the cell cycle by affected neurons. However, while such a cell cycle re
      entry phenotype is an early and consistent feature of Alzheimer disease, the
      mechanisms responsible for neuronal cell cycle are unclear. In this regard, given
      that a dysregulated cell cycle is a characteristic of cancer, we speculated that
      alterations in oncogenic proteins may play a role in neurodegeneration. To this
      end, in this study, we examined brain tissue from cases of Alzheimer disease for
      the presence of BRCA1, a known regulator of cell cycle, and found intense and
      specific localization of BRCA1 to neurofibrillary tangles, a hallmark lesion of
      the disease. Analysis of clinically normal aged brain tissue revealed
      systematically less BRCA1, and surprisingly in many cases with apparent
      phosphorylated tau-positive neurofibrillary tangles, BRCA1 was absent, yet BRCA1
      was present in all cases of Alzheimer disease. These findings not only further
      define the cell cycle reentry phenotype in Alzheimer disease but also indicate
      that the neurofibrillary tangles which define Alzheimer disease may have a
      different genesis from the neurofibrillary tangles of normal aging.

PMID- 17505560
TI  - Relationships between free radical levels during carotid endarterectomy and
      markers of arteriosclerotic disease.
AB  - BACKGROUND: Free radical production is elevated in jugular venous blood emerging
      from the brain in conjunction with carotid endarterectomy. This study explores
      the relationships between markers for lesion progression in arteriosclerosis,
      production of radicals and clinical characteristics. METHODS: The radical
      production during carotid endarterectomy was studied in 13 patients with an ex
      vivo spin trap method using OXANOH as a spin trap. MCP-1, ICAM-1, MMP-9 and oxLDL
      were determined in venous blood samples before, during and after clamping of the
      carotid artery. Principal component analysis (PCA) as well as partial least
      square regression analysis (PLS) was applied to interpret the data. RESULTS: PCA
      and PLS analysis revealed that high values of MMP-9 and low values of ICAM-1 were
      associated with high radical production whereas MCP-1 and oxLDL were not
      correlated to radical production. MMP-9 was elevated at diabetes, high
      haemoglobin, high leucocyte counts and thrombocyte counts as well as at
      contralateral stenosis, whereas ICAM-1 showed reversed relationships to these
      clinical variables. MCP-1 increased during surgery. CONCLUSIONS: The main finding
      in our study is that MMP-9 in plasma is asscociated with radical production
      during carotid endarterectomy, suggesting that this enzyme might be involved in
      the pathogenesis of brain damage in conjunction with ischaemia-reperfusion.

PMID- 17505561
TI  - Middle-ear transmission in humans: wide-band, not frequency-tuned?
AB  - Postmortem and in vivo vibration responses to sound of the stapes and the umbo of
      human ears are surveyed. The magnitudes of umbo velocity responses recorded
      postmortem decay between 1 and 5 or 10 kHz at rates between 0 and -3 dB/octave.
      In contrast, the magnitudes of in vivo umbo vibration are relatively invariant
      over a wide frequency range, amply exceeding the bandwidth of the audiogram
      according to one report. Similarly, most studies of postmortem stapes vibration
      report velocities tuned to about 1 kHz, with magnitudes that decay at a rate of
      about -6 dB/octave at higher frequencies. In contrast, in vivo stapes responses
      are apparently only mildly tuned. We conjecture that the bandwidth of stapes
      vibration velocity in humans will eventually be shown to exceed the bandwidth of
      the audiogram, in line with findings in other amniotic vertebrates.

PMID- 17505562
TI  - Quality indicators in colonoscopy.

PMID- 17505563
TI  - Is Helicobacter pylori being treated appropriately? A study of inpatients and
      outpatients in a tertiary care centre.
AB  - BACKGROUND: Helicobacter pylori is causally associated with peptic ulcer disease
      and gastric cancer. Although effective treatment is available, studies have shown
      that patients with H pylori are often not well managed. Recently, there has also
      been increasing awareness of patient safety concerns arising from missed follow
      up of abnormal test results. OBJECTIVE: To examine whether inpatients and
      outpatients diagnosed with H pylori receive appropriate treatment. PATIENTS AND
      METHODS: All patients who were diagnosed with H pylori by gastric biopsy in
      London, Ontario between January 1, 2004, and December 31, 2004, were identified.
      The hospital charts of these patients were reviewed. Outpatient office charts,
      clinic notes, pathology reports and endoscopy reports were also reviewed.
      RESULTS: One hundred ninety-three patients were diagnosed with H pylori by
      gastric biopsy in 2004. Of the 193 patients, 143 (74%) were outpatients and 50
      (26%) were inpatients. Overall, 89% of patients received treatment for H pylori.
      Ninety-two per cent of outpatients were treated, while only 60% of inpatients
      received treatment (P<0.001). Among the inpatients, the pathology report was
      available in 40% of the cases before the patient was discharged from the
      hospital. After discharge from the hospital, 30% of inpatients received
      appropriate treatment and follow-up. There was no significant difference in
      treatment whether the patient was admitted to a medical or a nonmedical service.
      CONCLUSION: H pylori is treated relatively poorly in inpatients compared with
      outpatients. Results of the present study reveal opportunities to improve
      delivery of care for inpatients on a number of different levels. More research is
      needed to ensure safety, effectiveness and timeliness in the test result
      management process.

PMID- 17505564
TI  - Association between leptin, metabolic factors and liver histology in patients
      with chronic hepatitis C.
AB  - BACKGROUND: Steatosis is common in hepatitis C virus (HCV)-infected patients and
      likely accelerates fibrosis progression. Leptin, the peptide product of the
      obesity gene (ob), has been implicated in hepatic fibrogenesis; circulating
      levels of leptin correlate with body fat mass. The objective of the present study
      was to determine the clinical and histological correlates of serum leptin in HCV
      infected patients, and to determine its utility in predicting liver histological
      lesions. PATIENTS AND METHODS: In 62 patients with chronic HCV, serum leptin was
      measured using a commercially available immunoassay. Associations between leptin,
      metabolic parameters, and severe hepatic fibrosis (stages 2 to 4) and steatosis
      (30% or greater) were determined. The utility of leptin in predicting liver
      histology was determined using receiver operating characteristic (ROC) curves.
      RESULTS: The median body mass index (BMI) was 23.2 kg/m2 (range 17.7 kg/m2 to
      35.6 kg/m2); 16% of patients (n=10) had HCV genotype 3. Severe fibrosis and
      steatosis were present in 23% and 13% of patients, respectively. Leptin was
      strongly correlated with the BMI, and its levels were higher in women. BMI
      corrected leptin levels were not independently associated with severe fibrosis
      but were significantly associated with steatosis (OR of 1.07; 95% CI 1.01 to
      1.04). On it own, leptin was poorly predictive of severe steatosis (area under
      the ROC curve was 0.64; 95% CI 0.42 to 0.87). However, its accuracy improved with
      the addition of HCV genotype (area under the ROC curve was 0.86; 95% CI 0.72 to
      1.00; P=0.07). CONCLUSIONS: As observed in the non-HCV setting, serum leptin
      correlates with BMI; higher leptin levels are found in women than men with
      chronic HCV. Serum leptin is a poor predictor of HCV-related fibrosis but may
      play a role in predicting steatosis when combined with HCV genotype.

PMID- 17505565
TI  - A meta-analysis of the success rate of Helicobacter pylori therapy in Canada.
AB  - BACKGROUND AND AIM: Helicobacter pylori treatment success rates have varied. A
      systematic review of the success rate of anti- H pylori therapy in Canada was
      performed. METHODS: All clinical trials containing Canadian data on the success
      rate of H pylori treatment were identified using MEDLINE searches, through review
      of references of retrieved studies and by contacting key investigators. Both
      randomized and open-label trials were included. Treatment effect size was
      calculated using a variation of Cochran's Q method. RESULTS: Seventeen papers met
      the inclusion criteria. Both triple therapies consisting of a proton pump
      inhibitor (PPI), clarithromycin and either amoxicillin or metronidazole performed
      well, achieving a success rate of 84% and 82%, respectively. The cure rate of PPI
      amoxicillin + metronidazole was 76%. Quadruple therapy consisting of a PPI,
      bismuth, metronidazole and tetracycline, given for seven to 10 days, achieved a
      success rate of 87%. CONCLUSION: Both PPI-based triple therapy and quadruple
      therapy perform well in Canada for the treatment of H pylori infection.

PMID- 17505566
TI  - Referring patients to nurses: outcomes and evaluation of a nurse flexible
      sigmoidoscopy training program for colorectal cancer screening.
AB  - Colorectal cancer is a significant health burden. Several screening options exist
      that can detect colorectal cancer at an early stage, leading to a more favourable
      prognosis. However, despite years of knowledge on best practice, screening rates
      are still very low in Canada, particularly in Ontario. The present paper reports
      on efforts to increase the flexible sigmoidoscopy screening capacity in Ontario
      by training nurses to perform this traditionally physician-performed procedure.
      Drawing on American, British and local experience, a professional regulatory
      framework was established, and training curriculum and assessment criteria were
      developed. Training was initiated at Princess Margaret Hospital and Sunnybrook
      and Women's College Health Sciences Centre in Toronto, Ontario. (During the
      study, Sunnybrook and Women's College Health Sciences Centre was deamalgamated
      into two separate hospitals: Women's College Hospital and Sunnybrook Health
      Sciences Centre.) Six registered nurses participated in didactic, simulator and
      practical training. These nurses performed a total of 77 procedures in patients,
      23 of whom had polyps detected and biopsied. Eight patients were advised to
      undergo colonoscopy because they had one or more neoplastic polyps. To date, six
      of these eight patients have undergone colonoscopy, one patient has moved out of
      the province and another patient is awaiting the procedure. Classifying the six
      patients according to the most advanced polyp histology, one patient had a
      negative colonoscopy (no polyps found), one patient's polyps were hyperplastic,
      one had a tubular adenoma, two had advanced neoplasia (tubulovillous adenomas)
      and one had adenocarcinoma. All these lesions were excised completely at
      colonoscopy. Overall, many difficulties were anticipated and addressed in the
      development of the training program; ultimately, the project was affected most
      directly by challenges in encouraging family physicians to refer patients to the
      program. As health human resource strategies continue to evolve, it is believed
      that lessons learned from experience make an important contribution to the
      knowledge of how nontraditional health services can be organized and delivered.

PMID- 17505567
TI  - Hepatic portal venous gas: a report of two cases and a review of the
      epidemiology, pathogenesis, diagnosis and approach to management.
AB  - BACKGROUND: Hepatic portal venous gas (HPVG) is a rare condition that occurs when
      intraluminal gas and/or gas produced by intestinal bacteria enters the portal
      venous circulation. The most common precipitating factors include ischemia, intra
      abdominal abscesses and inflammatory bowel disease. However, HPVG has recently
      been recognized as a rare complication of endoscopic and radiological procedures.
      Earlier studies advised immediate surgical intervention, but according to current
      recommendations, in some settings, HPVG can be managed conservatively. The
      present study reports two cases of HPVG; one that occurred following colonoscopy
      in a patient with severe Crohn's disease and one in a patient with graft-versus
      host disease. METHODS: The epidemiology, pathogenesis, diagnosis and management
      of HPVG are reviewed. Two case reports are presented, followed by the development
      of a management algorithm. RESULTS: Of the two patients that developed HPVG, one
      was an outpatient undergoing a colonoscopy for assessment of Crohn's disease
      activity and the other was an inpatient with graft-versus-host disease. Once the
      diagnosis of HPVG was made, both patients were managed conservatively with
      antibiotic therapy and management of their underlying disease. CONCLUSIONS: HPVG
      can occur in the setting of severe gastrointestinal disease states and following
      endoscopic procedures. It is critical that gastroenterologists are aware of the
      differential diagnosis, pathogenesis, diagnostic approach and management of HPVG.

PMID- 17505568
TI  - Evolution of collagenous colitis into severe and extensive ulcerative colitis.
AB  - Collagenous colitis is an inflammatory mucosal disorder of the colon with
      distinctive histopathological features, including a thickened subepithelial
      collagen layer. The clinical course is usually benign, but serious complications,
      including death, may occur. In the present report, a 69-year-old woman with
      watery diarrhea and collagenous colitis developed bloody diarrhea that was
      refractory to treatment medications, including corticosteroids and azathioprine.
      Endoscopic and histopathological studies showed a focal neutrophilic inflammatory
      process that progressed to a diffuse and extensive form of colitis, eventually
      requiring total proctocolectomy. Careful histological review of the resected
      colon showed no evidence of persistent collagenous colitis. These findings
      suggest an important need for continued long-term follow-up of patients with
      collagenous colitis because superimposed and serious colonic complications may
      occur, including a severe and extensive pancolitis refractory to medications and
      necessitating total proctocolectomy.

PMID- 17505569
TI  - Use of gabapentin for perioperative pain control -- a meta-analysis.
AB  - BACKGROUND: Gabapentin, an anticonvulsant, has recently been suggested as an
      effective postoperative 'analgesic' agent. The objective of the present study was
      to examine the analgesic effectiveness, opioid-sparing effects and side effects
      associated with the use of gabapentin in a perioperative setting. METHODS:
      Following the Quality of Reporting of Meta-analyses recommendations, nine
      electronic databases until February 2006 were searched, without language
      restriction, for randomized controlled trials comparing gabapentin with control
      for postoperative pain control. Outcome measures, namely, 24 h cumulative opioid
      consumption, visual analogue scale pain scores and adverse effects, were
      expressed as odds ratios, ratio of means or weighted mean differences (as
      appropriate), which were aggregated under the fixed or random effects models.
      RESULTS: Gabapentin caused a 35% reduction in total opioid consumption over the
      first 24 h following surgery (ratio of means 0.65, 95% CI 0.59 to 0.72), a
      significant reduction in postoperative pain at rest (in the first 24 h) and with
      movement (at 2 h, 4 h and 12 h), regardless of whether treatment effects were
      expressed as ratios of means or weighted mean differences, and a reduction of
      vomiting (relative risk [RR] 0.73, 95% CI 0.56 to 0.95) and pruritus (RR 0.30,
      95% CI 0.13 to 0.70). It was associated with a significant increase in dizziness
      (RR 1.40, 95% CI 1.06 to 1.84) and an increase in sedation of borderline
      significance (RR 1.65, 95% CI 1.00 to 2.74). CONCLUSION: Gabapentin improves the
      analgesic efficacy of opioids both at rest and with movement, reduces analgesic
      consumption and opioid-related adverse effects, but is associated with an
      increased incidence of sedation and dizziness.

PMID- 17505570
TI  - Pain characteristics and demographics of patients attending a university
      affiliated pain clinic in Toronto, Ontario.
AB  - BACKGROUND: Pain clinics tend to see more complex chronic pain patients than
      primary care settings, but the types of patients seen may differ among practices.
      OBJECTIVE: The aim of the present observational study was to describe the pain
      and demographic characteristics of patients attending a university-affiliated
      tertiary care pain clinic in Toronto, Ontario. METHODS: Data were collected on
      1242 consecutive new patients seen over a three-year period at the Comprehensive
      Pain Program in central Toronto. RESULTS: Musculoskeletal problems affecting
      large joints and the spine were the predominant cause of pain (more prevalent in
      women), followed by neuropathic disorders (more prevalent in men) in patients
      with recognizable physical pathology. The most affected age group was in the 35-
      to 49-year age range, with a mean pain duration of 7.8 years before the
      consultation. While 77% of the Comprehensive Pain Program patients had relevant
      and detectable physical pathology for pain complaints, three-quarters of the
      overall study population also had significant associated psychological or
      psychiatric comorbidity. Women, in general, attended the pain clinic in greater
      numbers and had less apparent physical pathology than men. Finally, less than one
      in five patients was employed at the time of referral. CONCLUSIONS: The relevance
      of the data in relation to other pain clinics is discussed, as well as waiting
      lists and other barriers faced by chronic pain patients, pain practitioners and
      pain facilities in Ontario and Canada.

PMID- 17505571
TI  - Ethnocultural and sex characteristics of patients attending a tertiary care pain
      clinic in Toronto, Ontario.
AB  - BACKGROUND: Ethnocultural factors and sex may greatly affect pain perception and
      expression. Emerging literature is also documenting racial and ethnic differences
      in pain access and care. OBJECTIVE: To define the sex and ethnocultural
      characteristics of patients attending a tertiary care, university-affiliated pain
      clinic in Toronto, Ontario. METHODS: Data were collected on 1242 consecutive, new
      patients seen over a three-year period at the Comprehensive Pain Program (CPP) in
      downtown Toronto. Data were compared with the Canada 2001 Census. RESULTS:
      English-speaking, Canadian-born patients constituted 58.6% of the CPP population,
      similar to the 2001 Canadian Census data for the Greater Toronto Area. Certain
      visible minority groups (Indo-Pakistani and Chinese) were significantly under
      represented, while European groups were over-represented. While women outnumbered
      men, they presented with lower levels of physical pathology in general,
      particularly in certain ethnic groups. Patients from Europe (representing
      primarily immigrants who arrived in Canada before 1960), were older, by 10 years
      to 15 years, than the average CPP population, and had a much higher incidence of
      physical or medical disorders. CONCLUSIONS: The implications of the study and the
      importance of sex and ethnicity in terms of presentation to Canadian pain clinics
      are discussed. Future well-designed studies are needed to shed light on the role
      of both patients' and physicians' ethnicity and sex in pain perception and
      expression, decision-making regarding pain treatments and acceptance of pain
      treatments.

PMID- 17505572
TI  - [Extent of sperm DNA damage in spermatozoa from men examined for infertility.
      Relationship with oxidative stress].
AB  - BACKGROUND: Cryptorchidism and oligozoospermia are clinical conditions closely
      associated with impaired fertility. Oxidative stress and related sperm DNA damage
      have been identified as significant causes of male infertility. AIM: To determine
      the extent of sperm nuclear DNA damage in patients affected with idiopathic
      oligozoospermia or undescended testes and to examine its relationship with
      oxidative stress. PATIENTS AND METHODS: We studied 20 patients with idiopathic
      oligozoospermia and 18 with undescended testes (who previously underwent
      orchiopexy) and 25 normozoospermic healthy controls. All subjects underwent semen
      analysis. Sperm DNA damage was evaluated by the sperm chromatin structure
      assay/flow cytometry (SCSA-FCM) and by the dUTP-biotin nick end labeling (TUNEL)
      assay. Levels of reactive oxygen species (ROS) and total antioxidant capacity
      (TAC) were assessed by a chemiluminescence assay. RESULTS: DFI (percentage of
      sperm with denatured DNA) values and percentage of TUNEL positive cells were
      significantly greater in patients with oligozoospermia (DFI: 28.8+/-5.6; TUNEL+:
      26.9+/-3.0) or cryptorchidism (DFI: 26.4+/-10.1; TUNEL+: 29.1+/-3.9), compared
      with controls (DFI: 7.1+/-0.9; TUNEL+: 14.2+/-1.2). Similarly, both groups of
      patients had significantly higher (p<0.01) levels of ROS. TAC levels did not
      differ between control and patient groups, suggesting that the DNA damage occurs
      before spermiation. CONCLUSIONS: Sperm DNA damage is significantly increased in
      men with idiopathic oligozoospermia and in cryptorchid subjects. The finding of
      increased ROS levels may indicate that seminal oxidative stress may be involved
      in the pathogenesis of sperm DNA damage in these patients.

PMID- 17505573
TI  - [Prevalence of metronidazole, clarithromycin and tetracycline resistance in
      Helicobacter pylori isolated from Chilean patients].
AB  - BACKGROUND: Helicobacter pylori is a pathogenic bacterium that infects a
      significant number of individuals. At present, therapeutic strategies to
      eradicate this bacterium depend on our knowledge of its resistance to
      antimicrobials. AIMS: To evaluate the primary resistance of H pylori to
      metronidazole (Mtz), clarithromycin (Cla), and tetracycline (Tet) in symptomatic
      out-patients. MATERIAL AND METHODS: Fifty independent isolates of H pylori were
      obtained by endoscopy-assisted gastric biopsy from patients attending the
      University of Chile Clinical Hospital, that previously had not been treated with
      an eradication regime against this bacterium. The minimal inhibitory
      concentration of each antimicrobial was determined by agar dilution method.
      RESULTS: Forty five and 27% of the isolates were found to be resistant to Mtz and
      Tet, respectively; the majority of these resistant isolates were from patients
      older than 21 years. Twenty percent of isolates were resistant to Cla; these were
      distributed evenly among different ages. Thirty two percent of the isolates were
      resistant to two or more of the antimicrobials. CONCLUSIONS: The high frequency
      of naturally occurring, antimicrobial-resistant strains of H pylori poses a
      national and world-wide problem for public health.

PMID- 17505574
TI  - [Visceral adiposity and its association with serum lipids in female obese
      teenagers].
AB  - BACKGROUND: Increased visceral or abdominal adipose tissue in children and adults
      is strongly associated with metabolic and a variety of chronic diseases. AIM: To
      study the association between visceral or external body measurements of adiposity
      with blood lipids, glucose and insulin levels, in obese female adolescents.
      MATERIAL AND METHODS: In a cross-sectional study, 47 obese female adolescents
      (body mass index (BMI) >95th percentile) aged 10 to 15 years, were analyzed.
      Weight, height, BMI, Tanner pubertal stages, skinfold thickness, waist
      circumference, waist-to-hip ratio, fasting and 120 min post prandial blood
      glucose, serum insulin, and lipid profile were studied. Visceral fat was assessed
      by computed tomography at the L4-L5 level, measuring the fat area or the length
      of a straight drawn line between the spine and the internal border of the rectus
      abdominus muscle. RESULTS: No association between lipid profile and BMI or
      external body measurements (skinfold thickness, waist circumference, waist-to-hip
      ratio) was observed. Total serum cholesterol >170 mg/dL was positively associated
      with the straight line over 63 mm (a cut-off obtained by ROC analysis (RR 2.64;
      1.15-6.08). This association was statistically significant in girls in Tanner I +
      II (n =21; Fisher, p <0.023), but not with Tanner III + IV (n=26) stages.
      Increased cholesterol (>170 mg/dL) was also positively associated with a serum
      insulin >17 uU/mL in the Tanner I + II group (Fisher p<0.05), but not with the
      homeostasis model assessment of insulin resistance (HOMA). CONCLUSIONS: No
      external body measurement of adiposity was associated to increased serum
      cholesterol in these obese female adolescents. Increased total cholesterol (>170
      mg/dL) was associated with visceral fat (evaluated through the straight line
      spina-rectus abdominus muscle), and also with a serum insulin >17 uU/ml in those
      teenagers with Tanner I or II pubertal stages.

PMID- 17505575
TI  - Influence of the glutathione s-transferase gene polymorphisms on the
      susceptibility to basal cell skin carcinoma.
AB  - BACKGROUND: The identification of groups at high risk is fundamental to determine
      preventive strategies for skin cancer. Destructive reactive oxygen species
      produced by UVA or chemical carcinogens are metabolized by a series of enzymes.
      Polymorphisms of genes encoding for these enzymes may produce defective proteins
      with a diminished ability to detoxify a wide range of carcinogens. AIMS: To
      ascertain the influence and potential interactions of several polymorphisms of
      genes encoding four important antioxidant GST enzymes in the susceptibility to
      cancer among Brazilians. MATERIAL AND METHODS: We compared the genotypes of
      Glutathione S-Transferase mu, theta, pi and omega (GSTM1, GSTT1, GSTP1 and GSTO2)
      in a group of 102 patients with skin lesions and 124 controls. RESULTS: Patients
      with Basal Cell Skin Carcinoma (BCC) presented the combined GSTM1-GSTT1+ genotype
      more frequently (49.1%) than controls (29.8%) (Fisher test; p=0.04), conferring a
      2.273 (Odds Ratio; 95% CI=1.199-4.308) higher risk for BCC. We were not able to
      find any other association between genotypes or between any genotype and the
      patients' clinical features. CONCLUSIONS: The GST profile may help identify
      Brazilian individuals at higher risk for BCC.

PMID- 17505576
TI  - [Mechanical ventilatory parameters guided by the low flow pressure-volume curve
      in patients with acute lung injury/acute respiratory distress syndrome].
AB  - BACKGROUND: Mechanical ventilation may contribute to lung injury and then enhance
      systemic inflammation. Optimal ventilatory parameters such as tidal volume (VT)
      and positive end expiratory pressure (PEEP) can be determined using different
      methods. Low flow pressure volume (P/V-LF) curve is a useful tool to assess the
      respiratory system mechanics and set ventilatory parameters. AIM: To set VT and
      PEEP according P/V-LF curve analysis and evaluate its effects on gas exchange and
      hemodynamic parameters. MATERIALS AND METHODS: Twenty seven patients underwent
      P/V-LF within the first 72 hours of acute lung injury/acute respiratory distress
      syndrome (ALI/ARDS). P/V-LF curves were obtained from the ventilator and both
      lower and upper inflexion points determined. Gas exchange and hemodynamic
      parameters were measured before and after modifying ventilator settings guided by
      P/V-LF curves. RESULTS: Ventilatory parameters set according P/V-LF curve, led to
      a rise of PEEP and reduction of VT: 11.6+/-2.8 to 14.1+/-2.1 cm H2O, and 9.7+/
      2.4 to 8.8+/-2.2 mL/kg (p<0.01). Arterial to inspired oxygen fraction ratio
      increased from 158.0+/-66 to 188.5+/-68.5 (p<0.01), and oxygenation index was
      reduced, 13.7+/-8.2 to 12.3+/-7.2 (p<0.05). Cardiac output and oxygen delivery
      index (IDO2) were not modified. Demographic data, gas exchange improvement and
      respiratory system mechanics showed no significant difference between patients
      with extra-pulmonary and pulmonary ALI/ARDS. There was no evidence of significant
      adverse events related with this technique. CONCLUSION: P/V-LF curves information
      allowed us to adjust ventilatory parameters and optimize gas exchange without
      detrimental effects on oxygen delivery in mechanically ventilated ALI/ARDS
      patients.

PMID- 17505577
TI  - [A predictive model for the quality of sexual life in hysterectomized women].
AB  - BACKGROUND: The effects of hysterectomy on sexuality has been extensively
      studied. AIM: To establish a model to predict the quality of sexual life in
      hysterectomized women, six months after surgery. MATERIAL AND METHODS:
      Analytical, longitudinal and prospective study of 90 hysterectomized women aged
      45+/-7 years. Two structured interviews at the time of surgery and six months
      later were carried out to determine the characteristics of sexuality and
      communication within the couple. RESULTS: In the two interviews, communication
      and the quality of sexual life were described as "good" in 72 and 77% of women,
      respectively (NS). The variables that had a 40% influence on the quality of
      sexual life sixth months after surgery, were oophorectomy status, the presence of
      orgasm, the characteristics of communication and the basal sexuality with the
      couple. CONCLUSIONS: The sexuality of the hysterectomized women will depend, on a
      great extent, of pre-surgical variables. Therefore, it is important to consider
      these variables for the education of hysterectomized women.

PMID- 17505578
TI  - [Social and familial determinants of anxiety and depressive symptoms in middle to
      low income women].
AB  - BACKGROUND: Among women, risk factors for mental disorders are violence,
      economical inequities and disadvantages and discrimination. AIM: To determine the
      prevalence of anxiety and depressive symptoms in women and to determine factors
      associated with them. MATERIAL AND METHODS: A cross sectional study of a
      probabilistic sample of 422 women aged 34 years as a mean, living in a medium to
      low income neighborhood in Temuco, Chile. Mental health was assessed with the
      self reporting questionnaire (SRQ20), partner violence was evaluated using a 12
      item scale and family conflict and violence was evaluated using the Conflicts
      Tactics scale. A logistic repression analysis was used to identify factors
      associated with mental health alterations. RESULTS: Forty one percent of women
      had anxiety or depressive symptoms. The main associated factors with these
      symptoms were severe physical violence against children (odds ratio (OR)=14.3),
      sexual violence against women (OR=9.7), self perception of health (OR=4.5),
      alcohol abuse (OR=4.4), psychological violence during childhood (OR=3.2) and lack
      of family support network (OR=2.7). Unemployment and lack of a support network of
      relatives had an OR 3.3 for mental health alterations. The OR for psychological
      violence plus sexual violence was 18.5. The figure for psychological violence
      plus sexual violence plus a history of parental violence during childhood was
      26.5. CONCLUSIONS: Forty one percent of this group of women had mental health
      alterations. There is a strong association between these alterations, family
      violence and socioeconomic factors.

PMID- 17505579
TI  - [Saliva and plasma levels of carbamazepine have a poor correlation: a pilot
      study].
AB  - Carbamazepine is one of the most commonly used anticonvulsants for the treatment
      of epilepsy and its plasma concentrations must be monitored periodically to
      obtain a useful and safe clinical effect. There is not a good relationship
      between the dose of the carbamazepine and their effects in humans, but the
      effects of this drug have been well correlated with its plasma levels. AIM: To
      measure the correlation between plasma and saliva levels of carbamazepine in
      children with epilepsy. MATERIAL AND METHODS: Saliva and plasma levels of
      carbamazepine were measured by using instrumental planar chromatography in 11
      epileptic children aged 8 to 15 years treated with the drug for at least six
      months. RESULTS: The mean saliva/plasma ratio was 0.18+/-0.05 and the mean of
      carbamazepine concentration in saliva, expressed as a percentage of
      concentrations in plasma, was 17.97+/-5.40. There was a poor linear correlation
      (r=0.37) between the concentrations of carbamazepine in both fluids. CONCLUSIONS:
      In this group of epileptic children the correlation between saliva and plasma
      carbamazepine levels was weak.

PMID- 17505581
TI  - [Percutaneous inferior vena cava filters: indications and results in 287
      patients].
AB  - BACKGROUND: Anticoagulation is the treatment of choice for deep vein thrombosis
      (DVT) and pulmonary embolism (PE). Occasionally this treatment is contraindicated
      or fails to prevent PE. In these patients, inferior vena caval (IVC) interruption
      is indicated and insertion of a filter is the most commonly performed procedure.
      AIM: To report the experience with IVC filters. MATERIAL AND METHODS:
      Retrospective review of all medical records and operative protocols of patients
      subjected to IVC filter implantations. Follow up was performed by telephone
      contact with the patient, relatives or primary physicians, ambulatory
      consultation or by death certificates. RESULTS: During the period 1993-2005 we
      implanted IVC filters on 287 patients, 55.4% male, average age: 62.1 yrs (17-99).
      Indications for the procedure were DVT or PE and contraindication of
      anticoagulation in 141 patients (49.1%), DVT or PE and complication of
      anticoagulation in 65 patients (22.6%), prophylaxis in 39 patients (13.6%),
      massive PE or poor respiratory function in 31 patients (10.8%), paradoxal emboli
      in 4 patients (1.4%) and other causes in seven patients. All percutaneous devices
      were successfully inserted. There was no morbidity or mortality related to the
      procedure. The most frequent access site was the internal jugular vein (66.6%).
      In 24 patients (8.4%) the filter was intentionally deployed above the renal
      veins. Six patients (2.1%) were lost to follow up after discharge. A mean follow
      up of 41.5 months was achieved. Ninety one patients died, with a 5 years survival
      of 64.7%. Symptomatic recurrent PE occurred in 6 patients (2.1%) and was the
      cause of death on 3 of them (1%), DVT has been detected in 22 patients (7.7%)
      during the follow up period. CONCLUSIONS: IVC filter implantation is a safe and
      effective short and long term measure to prevent PE and its consequences.

PMID- 17505580
TI  - [Hodgkin lymphoma in Chile: experience of the national adult cancer program].
AB  - BACKGROUND: Hodgkin lymphoma is a highly curable disease. AIM: To evaluate the
      clinical characteristics and the treatment results of Hodgkin lymphoma patients
      of the National Cancer Program in Chile. PATIENTS AND METHODS: Prospective
      assessment of 682 patients treated in 18 adult cancer centers. Progression free
      survival (PFS) and overall survival (OS) were calculated. Median follow up was
      127, 95, 87, 72 and 50 months for C-MOPP, radiotherapy (RT), C-MOPP/ABV, NOVP and
      ABVD, respectively. RESULTS: Median age was 37 years (15-84). Nodular sclerosis
      and mixed cellularity were equally expressed. Advanced stages (III & IV) were
      present at diagnosis in 61% of cases. Age over 40 was an adverse prognostic
      factor (p<0.001). The rate of PFS at 5 and 10 years for early stages was 73% and
      66% with RT, 80% and 74% with C-MOPP+RT, 73% and 71% with C-MOPP/ABV, 59% and 59%
      with NOVP+RT, and 81% with ABVD+RT, at 5 years, being significantly lower for
      NOVP (p=0.02). The rate of OS at 5 and 10 years for advanced stages was 82% and
      70% with RT, 82% and 76% with C-MOPP+RT, 82% and 80% with C-MOPP/ABV, 68% and 60%
      with NOVP, and 85% with ABVD at 5 years, also significantly lower for NOVP
      (p=0.04). For advanced stages, the rate of PFS at 5 and 10 years was 49% and 43%
      with C-MOPP, 69% and 62% with C-MOPP/ABVD or C-MOPP/ABV, and 71% at 5 years with
      ABVD, significantly lower for C-MOPP (p=0.01). The rate of OS at 5 and 10 years
      was 52% and 46% with C-MOPP, 70% and 63% with C-MOPP/ABVD or C-MOPP/ABV and 76%
      with ABVD at 5 years, significantly lower for C-MOPP (p=0.0002). CONCLUSIONS: Age
      over 40 years was an adverse prognostic factor. C-MOPP/ABVD, C-MOPP/ABV and ABVD
      had comparable results and reached a high tumor control and overall survival in
      both early and advanced stages.

PMID- 17505582
TI  - [Hypocalcemic cardiomyopathy secondary to hypoparathyroidism after a
      thyroidectomy: report of one case].
AB  - Calcium plays a central role in ventricular function. We report a 37 year-old
      woman with chronic hypoparathyroidism and hypocalcemia secondary to a
      thyroidectomy performed when she was 18 years old, as treatment for a Graves
      Basedow's disease. She did not have previous cardiac symptoms and rapid
      progressive congestive heart failure developed after the beginning of
      levothyroxin supplementation for post operative hypothyroidism. Echocardiography
      revealed severe systolic and diastolic left ventricular dysfunction, mitral and
      tricuspid valve insufficiency, systolic pulmonary hypertension, left atrial
      enlargement and pericardial effusion. Calcium supplementation in addition to
      diuretics, captopril and digoxin were followed by rapid clinical improvement.
      Follow up until 18 months showed persistent left ventricular dilatation and
      systolic dysfunction, with improvement of all the other echocardiographic
      findings.

PMID- 17505583
TI  - [Renal angioplasty with stent using CO2 as contrast medium: report of one case].
AB  - Revascularization procedures for atherosclerotic renovascular hypertension are
      aimed to improve or cure hypertension and to reduce the progression to ischemic
      nephropathy and renal failure. Renal angioplasty is the preferred method, but a
      common complication is contrast-induced nephropathy. To avoid or lessen this
      complication, CO2 can be used as a contrast medium. We report a 68 year-old woman
      with renovascular hypertension and mild deterioration of renal function in whom
      we implanted an stent using digital substraction angiography and CO2 as contrast
      medium, which was injected manually. We obtained satisfactory images and we ended
      the procedure without complications. Blood pressure fell and creatinine levels
      did not change.

PMID- 17505584
TI  - [Cyclosporine-induced gingival hyperplasia: report of one case].
AB  - Gingival enlargement can be an adverse effect of cyclosporine A and nifedipine
      use. It has a high relapse rate if the drugs are not discontinued. There is a
      genetic predisposition to the development of this condition and dental biofilm
      can also play a role. We report a 64 years old male who received a renal
      allograft and was treated with cyclosporine and nifedipine. He required six
      surgical interventions for generalized gingival enlargement. After the sixth
      relapse, the patient was subjected to a periodontal treatment to eliminate the
      dental biofilm, which decreased the rate of recurrence of gingival enlargement.

PMID- 17505585
TI  - [Chilean experience with the use of 18F-deoxyglucose positron emission
      tomography].
AB  - BACKGROUND: Clinical oncology is the main application of 18F-deoxyglucose (FDG)
      positron emission tomography (PET). AIM: To evaluate the first 1,000 patients
      studied with FDG PET in Chile. MATERIAL AND METHODS: Retrospective analysis of
      1,000 patients (aged between 1 and 94 years, 550 females) studied with FDG PET,
      since 2003. All studies were performed in a high resolution Siemens Ecat-Exact HR
      (+). All reports were based on the visual analysis of three plane and three
      dimensional images. RESULTS: Ninety seven percent of exams were done for
      oncological indications, mainly lung lesions, lymphoma, colorectal and
      gastroesophageal, cancer and breast tumors. Only 1% of patients had brain tumors.
      Non tumor neurological indications corresponded to 1.7%. Cardiac studies were
      only 0.3% and inflammatory process corresponded to 1%. The 5.6% corresponded to
      pediatric population. Six percent of patients were aged less than 18 years and in
      50% of them, the indication was oncological, mainly lymphomas, brain tumors,
      endocrine cancers and sarcomas. The remaining 50% had a neurological indications,
      mainly for refractory epilepsy. CONCLUSIONS: PET FDG imaging was effective in the
      management of diverse diseases of children and adults.

PMID- 17505586
TI  - [Update in the clinic of addictions: learning and dopamine].
AB  - There are two parallel explanatory models for addictions. One is the homeostatic
      model, that explains tolerance and the abstinence syndrome. Tolerance and
      abstinence are reversible phenomena that mask sensitization. These appear more
      commonly with the continued use of drugs, and are based in the up-regulation of
      cyclic AMP. The other is the plasticity model, that explains sensitization and
      compulsive use of drugs or addiction. Addiction is probably irreversible,
      underlies tolerance, appears more frequently with intermittent use of drugs, and
      is based in learning and memory mechanisms. Both are boldly linked to
      environmental and behavioral elements. In the plasticity model, dopamine (DA) has
      an outstanding role. Its phasic discharge is a temporal reward prediction error
      marker. It is the prediction error that generates learning. All the addictive
      drugs provoke a very strong increase of phasic DA discharge in some cerebral
      nuclei by direct or indirect paths. This increase is interpreted by cerebral
      circuits as prediction errors that generate learning behaviors. Pavlovian and
      operating type learning is involved. It is clinically observed as the prominence
      of environmental cues that are related to drug consumption, and the appearance of
      behaviors directed to the search and use of drugs, that are mainly involuntary
      and triggered by these cues. Pleasure (primary reinforcement) plays a role in
      this model, only in the initial stages of addiction. Understanding this double
      parallel model allows to design therapeutic interventions directed towards a
      conscious control of involuntary, environmental and affective cues that trigger
      drug search and use.

PMID- 17505587
TI  - [Health policies for older adults: thoughts for action].
AB  - The speed of growth of the population of older adults has been much faster than
      expected in every country. In Chile today one out of ten persons is an older
      adult and in the next twenty years this proportion will duplicate. Population
      aging is a success of development but also presents a medical and social
      challenge. The health issues of the National Policy addressing the needs of the
      older population in Chile are severely delayed in their implementation due to the
      lack of human resources trained in medicine of older adults and geriatric
      services. The consensus evidence on how to develop appropriate geriatric health
      services for older adults should include services coordinated in a continuum,
      including health promotion and disease prevention targeting older people to
      achieve "healthy aging" in the majority of the older population; outpatient
      health care services; acute care in hospitals with physicians trained in
      geriatrics; special services for geriatric rehabilitation and restoration of
      function (short term care) and a variety of settings and services offering long
      term care ranging from home to institutions. To be able to implement this vision
      of appropriate, coordinated and integrated health and social services for older
      people, the country needs a minimum number of geriatricians (at least 260),
      health care teams trained in the basics of geriatrics and continuing development
      of human resources to meet the increasing demand on health services by the fast
      growing older population.

PMID- 17505588
TI  - [The neurological disorder of Georg Friedrich Handel].
AB  - Georg Friedrich Handel, a musical genius, was affected since his middle age by
      several attacks, during a period of 20 years, of upper right limb palsies,
      abnormal speech followed by amaurosis in his contralateral eye and then is both
      eyes. He underwent three unsuccessful operations due to a wrong diagnosis of
      cataracts. We discuss the possible differential diagnoses. Considering his clear
      vascular profile, the most plausible hypothesis is cerebrovascular disease with
      embolic infarcts from stenotic left internal carotid artery to the left middle
      cerebral and retinal arteries.

PMID- 17505589
TI  - [A screening questionnaire to evaluate infant and toddler development].

PMID- 17505590
TI  - [Mutation in LRRK2 is associated with familial presentation of Parkinson's
      disease in a Chilean kindred].

PMID- 17505591
TI  - Specific tests for nasal permeability.

PMID- 17505592
TI  - Changes in click characteristics during ABR recording.
AB  - Manipulation of auditory stimuli affect the ABR evoked potentials and aid the
      diagnosis, particularly in auditory neuropathy patients. Some patients with
      auditory neuropathy lose evoked otoacoustic emissions over time; in these cases,
      comparing responses to rarefaction and condensation clicks, and decreasing the
      stimulus rate can show an extended cochlear microphonism or yield an improved
      electric potential record. AIM: To analyze the effect of these click
      manipulations on the records of potentials of patients with hearing loss as a
      form of improving the diagnosis. STUDY DESIGN: A clinical prospective study.
      PATIENTS AND METHOD: 59 patients with hearing loss underwent ABR recording using
      rarefaction and condensation clicks at a stimulus rate of 27.7/sec, and
      rarefaction clicks at a stimulus rate of 3.3/sec. The records were compared to
      the otoacoustic evoked emission. RESULTS: Eight (13.53%) patients showed changes
      in the recorded ABR potentials as a result of manipulating the characteristics of
      clicks, such as extended cochlear microphonism or an improved record of electric
      potentials. Five patients had no otoacoustic evoked emissions. CONCLUSION:
      Manipulation of click stimuli can improve the topographic diagnosis of hearing
      loss, particularly in the group of auditory neuropathy patients with no
      otoacoustic evoked emissions, where usually, the diagnosis is only possible
      through the method described above.

PMID- 17505594
TI  - Analysis of helkimo and craniomandibular indexes for temporomandibular disorder
      diagnosis on rheumatoid arthritis patients.
AB  - AIM: The aim of this study was to evaluate the use of two indexes (Helkimo and
      Craniomandibular) for the diagnosis of temporomandibular disorder (TMD) in
      patients with Rheumatoid Arthritis (RA). PATIENTS AND METHODS: The sample was
      composed of 80 patients divided into two groups: patients with RA and patients
      without RA. In both groups the two indexes were used. For TMD diagnosis, the
      following signs and symptoms were evaluated: TMJ pain, limited mouth opening and
      joint sounds. RESULTS: Results showed that of the RA patients, 87.1% were females
      and 12.9% were males. Among the patients without RA, 70% were females and 30%
      were males. The age of these RA patients ranged between 24 and 78 years. Among
      patients without RA, the age of the patients ranged between 22 and 72 years. It
      was observed that the prevalence of TMD was higher in the group with RA (98.6%
      Helkimo and 87.1%-Craniomandibular) when compared to the group without the
      disorder (80%-Helkimo and 50%-Craniomandibular). CONCLUSION: In summary, one
      could conclude that both indexes are capable to diagnose temporomandibular
      disorders in RA patients, although the Helkimo index is less accurate.

PMID- 17505593
TI  - Optimizing the pharmacological component of integrated balance therapy.
AB  - Drug treatment is an important option for the treatment of peripheral vestibular
      diseases. AIM: To identify the drug component associated with optimal integrated
      balance therapy (IBT) for Menieres disease or other peripheral vestibular
      disorders. MATERIALS AND METHODS: Analysis of a series of patients with Menieres
      disease patients or patients with other peripheral vestibular disorders that
      received IBT involving either no medication or betahistine, cinnarizine,
      clonazepam, flunarizine or Ginkgo biloba during 120 days. RESULTS: In Menieres
      disease, significant differences were observed for all drug therapies (60 days)
      versus no medication; betahistine was significantly more effective than all other
      drugs at 60 and 120 days. For non-Menieres disorders, significant differences
      were observed among betahistine, cinnarizine, clonazepam and flunarizine and no
      medication after 60 days; all drug therapies were significantly more effective
      than no medication after 120 days; betahistine, cinnarizine or clonazepam were
      equally effective and betahistine was more effective than flunarizine and EGb
      761. All treatment options were well tolerated. CONCLUSIONS: Drug therapies were
      more effective than no medication in the IBT for patients with Menieres disease
      or other peripheral vestibular disorders. Betahistine was the most effective
      medication for patients with Menieres disease and was as effective as cinnarizine
      and clonazepam for other peripheral vestibular disorders.

PMID- 17505595
TI  - Profile of voice professionals seen in a tertiary health center.
AB  - Work-related laryngopathy may have negative consequences for voice professionals.
      AIM: To analyze the profile of voice professionals seen in a tertiary level
      hospital. STUDY DESIGN: a longitudinal historical cohort. METHODS: A
      retrospective analysis of patient files. Diagnosis was reached using
      videostroboscopy. RESULTS: 163 patients (119 females and 44 males) were seen. The
      mean age was 36.5 years. Professionals included spoken voice users (salesman,
      teachers, telemarketers, receptionists, health professionals) and singers. The
      most frequent diagnoses were: minor structural changes (33%), nodules (22%),
      Reinkes edema (10%), and polyps (6%). A correlation was observed between smoking,
      age and gender; there was an association between smoking and Reinkes edema,
      leucoplasia and tabagism, females and Reinkes edema, nodules and minor structural
      changes, and also between patients aged over 40 years and Reinkes edema, and
      patients under 40 with nodules, laryngitis, and minor structural changes.
      Symptoms lasted more than 6 months in 74% of patients. CONCLUSION: The profile of
      voice professionals seen in a tertiary hospital included spoken voice patients
      and singers. In our study minor structural changes predominated, followed by
      nodules, Reinke edema and polyps.

PMID- 17505596
TI  - Adult nasal volumes assessed by acoustic rhinometry.
AB  - Acoustic rhinometry allows an objective and non-invasive assessment of nasal
      geometry. AIM: The present study aimed at determining the volumes of specific
      segments of the nasal cavity in healthy adults including the nasopharynx, using
      acoustic rhinometry. STUDY DESIGN: A clinical prospective analysis. CASES AND
      METHOD: Thirty volunteers with no evidence of nasal obstruction, aged 18 to 30
      years (14 males and 16 females) were analyzed. Volumes were measured at the nasal
      valve region (V1), the turbinates (V2), and the nasopharynx (V3), before and
      after application of a topical nasal vasoconstrictor. RESULTS: The mean volumes
      measured in 60 cavities before nasal decongestion, were: 1.81+/-0.35 cm(3) (V1),
      4.02+/-1.41 cm(3) (V2), and 17.52+/-4.44 cm(3) (V3) for males, and 1.58+/-0.25
      cm(3) (V1), 3.94+/-1.03 cm(3) (V2), and 17.80+/-2.73 cm(3) (V3) for females.
      Gender differences were only significant in V1 (p<0.05). After nasal
      decongestion, the volumes of all the analyzed segments were significantly larger
      (p<0.05), and the gender differences were significant for V1 and V2. CONCLUSION:
      Volumes of the three segments in adults with no evidence of nasal obstruction may
      be used as reference values for other studies.

PMID- 17505597
TI  - Drooling: analysis and evaluation of 31 children who underwent bilateral
      submandibular gland excision and parotid duct ligation.
AB  - AIM: To evaluate the safety of bilateral submandibular gland excision and parotid
      duct ligation in order to control drooling in children; to assess its long-term
      efficacy and complications. STUDY DESIGN: longitudinal cohort. MATERIALS AND
      METHODS: Thirty-one children aged 6 to 13 years (7.6 years old in average), with
      multiple neurological disabilities were submitted to a bilateral submandibular
      gland excision with parotid duct ligation in order to control ptyalism between
      December 1999 and December 2005, mean follow up of 36 months. RESULTS: According
      to Wilkies success criteria, 87% of children had excellent or good results and
      insignificant morbidity was insignificant; with temporary parotid edema as the
      major complication. CONCLUSION: Bilateral submandibular gland excision with
      parotid duct ligation were safe to be performed in children, with 87% of success
      in drooling control.

PMID- 17505598
TI  - Cephalometric assessment of the hyoid bone position in oral breathing children.
AB  - MATERIAL AND METHODS: because of its anatomical and functional relationship with
      the craniofacial complex, we assessed the cephalometry of the hyoid bone position
      in relation to the respiratory pattern of these 53 female children, with average
      age of 10 years; 28 of them are nasal breathers and 25 are oral breathers.
      Horizontal, vertical and angular cephalometric measures were used in order to
      determine the hyoid bone location. The Student "t" and the Pearson correlation
      tests were used in order to compare the groups and the variables. RESULTS: We did
      not see statistically significant differences in mandible and hyoid bone
      positions and the respiratory pattern. In the hyoid triangle, the 0.40
      correlation coeficient was significant between AA-ENP (distance between the Atlas
      vertebrae and the posterior nasal spine) and C3-H (distance between the third
      cervical vertebrae and the hyoid bone) showing a positive relation between the
      bony limits of the upper and lower air spaces. For cranial measures we have
      suggested a relationship between the hyoid bone position and the mandible
      morphology. CONCLUSION: The results led us o conclude that the hyoid bone keeps a
      stable position, probably in order to secure correct ratios in the airways, and
      it does not depend on the respiratory pattern.

PMID- 17505599
TI  - Matrix metalloproteinase 2: an important genetic marker for cholesteatomas.
AB  - AIM: This study is to determine the MMP2s presence in cholesteatomas and whether
      complicating cholesteatomas show a higher immunohistochemical expression of
      matrix metalloproteinase 2. Cholesteatoma produces enzymes that cause bone
      erosion like matrix metalloproteinase 2 (MMP2). MATERIAL AND METHODS: We analyzed
      the expression of MMP2 in invasive (causing complications) compared to latent
      cholesteatomas (not causing complications). A cross-sectional study with nineteen
      slides and paraffin blocks of cholesteatomas derived from mastoidectomies were
      located and processed, including 8 invasive and 11 latent cholesteatomas.
      Immunohistochemical technique was empregated to MMP2. RESULTS: The results are
      expressed as 0, + (to low), ++ and +++(high) according to the quantity and color
      of the immunohistochemical staining of MMP2. Higher expression of MMP2 was
      observed in 7 (87.5%) of the 8 invasive cholesteatomas. With respect to latent
      cholesteatomas, higher expression of MMP2 was observed in 27.3% (3 cases), with
      Fishers exact test indicating a significant difference (p=0.015). CONCLUSIONS:
      Cholesteatoamas express MMP2 and Invasive cholesteatomas had high MMP2 compared
      to latent cholesteatomas.

PMID- 17505600
TI  - Hearing loss in aging.
AB  - Aging is a natural consequence of a society developing process. The city of Sao
      Paulo has almost one million people who are above sixty years of age. Age-related
      hearing loss equals the total hearing loss resulted from cell degeneration caused
      by noise exposure, ototoxic agents and the loss caused by disorders and medical
      treatments. AIM: To study age-related hearing degeneration by means of higher
      thresholds and hearing sensitivity measures. MATERIALS AND METHODS: Cross
      sectional contemporary cohort study in which we assessed 211 elderly patients
      with mean age of 75.24 years, of whom 61 were females and 150 were males. The
      subjects were submitted to an interview and a conventional audiometric
      assessment; and later divided into four groups according to age range. RESULTS:
      Significant threshold drop in the four established age groups, decrease in speech
      recognition ratio, and a significant difference regarding gender. CONCLUSION: As
      age advanced there was a gradual increase in hearing loss, men showed a lower
      threshold in the 4000 Hz frequency when compared to women, and in the speech
      intelligibility test there was also a gradual decrease with aging.

PMID- 17505601
TI  - The role of endoscopic surgery in the treatment of nasal inverted papilloma.
AB  - The inverted papilloma is a benign neoplasm, prone to malignancy, and bearing a
      high rate of post-op recurrence. There is much debate in the literature
      concerning the issue that an endoscopic approach may offer a benefit over an
      external approach. AIM: Demonstrate the efficacy of an endonasal endoscopic
      approach in the treatment of inverted papilloma. STUDY DESIGN: Retrospective.
      MATERIALS AND METHODS: Retrospective analysis of patients with inverted papilloma
      operated at the University Hospital--FMUSP from 1994 to 2004. RESULTS: Twenty
      eight patients records were studied. Nine patients (32.1%) had tumor recurrence,
      one being operated via the endoscopic method and eight by external approach.
      DISCUSSION: Krouses staging system for inverted papillomas can facilitate both
      treatment planning and comparison of surgical outcomes. The use of the endoscopic
      approach resulted in fewer relapses than when the external one was used in cases
      with the same tumor staging. CONCLUSION: The use of the endoscope in this type of
      surgical treatment is an important success factor in the treatment of inverted
      papilloma.

PMID- 17505602
TI  - Middle latency response study of auditory evoked potentials amplitudes and
      lantencies audiologically normal individuals.
AB  - Contemporary cohort cross-sectional study. INTRODUCTION: The auditory middle
      latency response (AMLR) is generated between 10 and 80 ms and has multiple
      generators, with a greater contribution from the thalamus-cortical pathways. The
      establishment of normality criteria for latency and amplitude values is necessary
      for clinical use. AIM: to analyze the latency and amplitude of the AMLR in
      individuals without audiological disorders, and verify the reliability of Pa-Nb
      amplitude. MATERIALS AND METHODS: The AMLR of 25 individuals was collected during
      2005 and the Na, Pa, Nb components were analyzed for each tested ear (A1 and A2),
      and electrode positioning (C3 and C4). RESULTS: A statistically significant
      difference was noticed among middle latency values for C3A1 and C4A1 regarding
      components Na and Pa, and no difference for component Nb and mean values for
      amplitudes Na-Pa and Pa-Nb. CONCLUSIONS: We established average and standard
      deviation values for latency and amplitude parameters for components Na, Pa, Nb
      and Na-Pa and Pa-Nb, under conditions C3A1, C4A1, C3A2, C4A2, providing a
      parameter for the analysis and interpretation of this potential.

PMID- 17505603
TI  - Acute sinusitis in children: a retrospective study of orbital complications.
AB  - Among the complications of sinusitis, those that involve the orbital region are
      the most frequent. AIM: the objective of this paper is to show an incidence of
      orbital cellulites (OC) secondary to acute sinusitis in children. STUDY DESIGN:
      retrospective. METHODS: After board approval, the charts of all pediatric
      patients diagnosed with orbital complications secondary to sinusitis, seen at the
      Pediatric and at the ENT clinics of the HPEV, between 1985 and 2004, were
      evaluated. The data was analyzed considering gender, age, clinical presentation,
      period of hospitalization, image study, and treatment. RESULTS: from 1985 to
      2004, 25 patients were diagnosed with OC secondary to sinusitis, presenting an
      incidence of 6% . Males predominated, the median age was 6.5 years, and the
      maxillary was the most frequently involved sinus. Twenty-four patients presented
      mild peri-orbital swallowing. All 25 patients presented X-Ray alterations. One
      patient with proptosis had a subperiosteal abcess seen on the CT-scan. The
      average time of hospitalization was 4 days. All 25 patients received IV
      antibiotics, 2 required surgery. CONCLUSION: The incidence of orbital
      complications secondary to sinusitis is low, and although the majority of cases
      are early diagnosed and respond well to medication treatment, a surgical
      intervention may be required.

PMID- 17505604
TI  - Surgical stoma recurrence after total laringectomy.
AB  - Stoma recurrence after total laryngectomy is one of the most severe developments
      of squamous cell carcinoma of the larynx. Risk factors most strongly implicated
      in stoma recurrence have been subglottic invasion by the laryngeal tumor and
      tracheotomy prior to laryngectomy. AIM: Study the clinical findings of patients
      who underwent total laryngectomy and evaluate the probable risk factors to the
      development of stoma recurrence. STUDY DESIGN: Descriptive and retrospective
      study MATERIALS AND METHODS: We studied data from 47 patients who underwent total
      laryngectomy for the treatment of laryngeal cancer between 1995 and 2004 and
      evaluated recurrences and risk factors. RESULTS: Stoma recurrence developed in
      10.6 per cent of them (5 cases). There was no significant correlation between
      stoma recurrence and subglottic invasion or prior tracheotomy. CONCLUSION: Stoma
      recurrence still is one of the most lethal developments associated to laryngeal
      cancer. In the present study it was not possible to identify factors related to
      this recurrence. Further studies with a larger sample and a longer follow-up
      period are necessary to better understand this condition.

PMID- 17505605
TI  - Cyclin D1 expression and cervical metastases in squamous cell carcinoma of the
      mouth.
AB  - Cervical metastasis represent the most relevant prognostic factor in carcinomas
      of the mouth. Clinical and histological factors are associated with the
      development of cervical metastasis; however, research on molecular factors has
      been broadly carried out in recent years. AIM: The aim of this study is to
      analyze the association of the Cyclin D1 as a risk factor for the presence of
      cervical metastasis. MATERIALS AND METHODS: Cyclin D1 expression was measured and
      the association between such substance and metastasis was found in 45 patients
      with mouth cancer treated by the author of this paper. Cyclin D1 presence was
      checked through the stereological method. Clinical and histological
      characteristics have been analyzed and associated with metastasis. RESULTS:
      Cyclin D1 expression was found in 15 patients but it was not associated with
      clinical and histological factors related to the presence of metastasis. Such
      conclusion indicates that Cyclin D1 is an independent protein. The most important
      predictive aspects related to metastasis development have been clinical staging
      and vascular embolization. CONCLUSIONS: Cyclin D1, although independent, is not
      associated with cervical metastasis, while staging and vascular embolization are.

PMID- 17505606
TI  - Lip reading role in the hearing aid fitting process.
AB  - Lip reading (LR) is unconsciously practiced as we communicate and has currently
      been widely used in the assessment of hearing impaired people. The hearing
      challenged individual is able "to read" lip position and thus interpret the
      speech sounds of the speaker; however, it is very likely that the best lip reader
      can only catch 50% of the words uttered. METHODOLOGY: 30 individuals of both
      gender, with age ranging from 27 to 89 years, carriers of moderate bilateral
      sensorineural hearing loss. The assessment encompassed speech recognition test of
      monosyllable words in four situations: without hearing aid (HA) and LR; without
      HA and with LR; with HA and without LR; and with HA and LR. RESULTS: we noticed
      an improvement in the percentage of correct answers in 93.5% of the patients with
      HA and LR when compared to those patients in the other situations. CONCLUSION:
      Lip reading is an important communication strategy for those with hearing
      impairment, and it can support the hearing aid fitting process.

PMID- 17505607
TI  - Otoneurologic findings in Type 1 Diabetes mellitus patients.
AB  - Metabolic alterations, as they occur in Diabetes mellitus, have been mentioned in
      the development and maintenance of complaints related to the vestibular and
      auditory organs. AIM: To investigate the vestibular system in Type 1 Diabetic
      mellitus population. MATERIAL AND METHOD: The present study was developed with 19
      individuals, being 10 females (52.6%) and 9 males (47.3%), with ages varying from
      8 to 25 years old, with medical diagnosis of Type 1 Diabetes mellitus. For result
      comparison, a control group was selected with others 19 individuals, matching the
      study group in age and gender. The evaluation protocol encompassed interview,
      otoscopic inspection, dynamic and static balance evaluation, cerebellar tests and
      vectoelectronystagmographic evaluation. STUDY DESIGN: Clinical prospective.
      RESULTS: Alteration in the vectoelectronystagmographic evaluation were found in
      36.84% (n=7) Type 1 Diabetes mellitus individuals, being 21.06% (n=4) Peripheral
      Deficiency Vestibular Syndrome and 15.79% (n=3) Peripheral Irritative Vestibular
      Syndrome. CONCLUSION: We conclude that Type 1 Diabetes mellitus individuals can
      have their vestibular organ affected, even if there are no otoneurologic
      complaints.

PMID- 17505608
TI  - Physical therapy in peripheral facial paralysis: retrospective study.
AB  - Peripheral facial paralysis requires specialized treatment. Physical therapy aims
      at reestablishing facial movements. The aim of this study was to describe and to
      analyze physical therapy results for individuals with peripheral facial
      paralysis. STUDY DESIGN: Retrospective study. METHOD: A retrospective study was
      carried out at the University Hospital, authorized by the Statistics and Medical
      File Services, from 1999 to 2003. Data are presented in descriptive form with
      mean and median values for numeric variables and frequency for categorical
      variables. RESULTS: Twenty-three files were analyzed during four years. Females
      predominated and the average age was of 32.3 years (SD+/-16.5); 14 idiopathic and
      five trauma cases; 12 with total motor deficit and 11 with partial motor deficit;
      in the 12 cases that underwent final evaluation, seven had partial and five had
      total recovery. The physical therapy program used was kinesiotherapy and patient
      education. CONCLUSION: In this study, individuals were similar to individuals in
      other populations. They were treated with kinesiotherapy, as suggested by the
      scientific literature and recovered.

PMID- 17505609
TI  - Alcoholism: effects on the cochleo-vestibular apparatus.
AB  - Several ototoxic drugs are harmful to the human being and lead to problems such
      as tinnitus, many types of hearing loss, and vertigo. Alcohol is among the main
      agents considered ototoxic. AIM: To study the effects of alcoholism in the
      vestibular-cochlear system. STUDY DESIGN: cross-sectional contemporary cohort.
      MATERIALS AND METHODS: The sample comprehended 37 individuals in the Experimental
      Group, members of Alcoholics Anonymous of the City Santa Maria-RS, and 37 non
      alcoholic individuals in the Control Group, age and gender matching. All of the
      individuals examined were submitted to anamnesis, otorhinolaryngological
      examination, basic hearing evaluation, and vecto-electronystamography. RESULTS:
      67.57% of the individuals from the Experimental Group showed abnormalities in the
      audiometry and 24.32% presented abnormalities in the computerized vecto
      electronystamography. In the Control Group, 27.03% of the individuals showed
      abnormalities in the audiometry and 10.81% presented abnormalities in the
      computerized vecto-electronystamography. CONCLUSION: Alcohol interferes on an
      individuals hearing and balance, causing deleterious effects on the human
      organism.

PMID- 17505610
TI  - The role of tumor necrosis factor-alpha (TNF-alpha) in bone resorption present in
      middle ear cholesteatoma.
AB  - Cholesteatoma may cause bone erosion, with high morbidity and mortality rates.
      Tumor necrosis factor-alpha (TNF-a) is one of the main cytokines involved in this
      process. Our goal was to evaluate the role of TNF-a in Bone Resorption and its
      effect on cholesteatoma. MATERIAL AND METHODS: analysis and critical literature
      review. RESULTS: Different studies have demonstrated that TNF-a is capable of
      causing bone erosion. It may stimulate the differentiation and maturation of
      osteoclasts or it may act on the bone matrix, exposing it to the action of the
      osteoclasts. It is possible to inhibit TNF-a, reducing its effects and prevent
      bone loss in illnesses such as rheumatoid arthritis,and there has been no
      specific investigation regarding cholesteatomas. All studies agree on the
      importance of TNF-a in the bone resorption process present in cholesteatomas, and
      on the degree of destruction observed; however, there is no consensus as to its
      location. These differences are probably due to receptor site. CONCLUSION: TNF-a,
      present in cholesteatomas, promotes bone resorption, along with other cytokines
      (RANKL and IL-1) related to complications.

PMID- 17505611
TI  - Audiology and aging: literature review and current horizons.
AB  - AIM: to review the literature on aging-related hearing loss and its current
      impacts. LITERATURE REVIEW: In studies carried out in Brazil, presbycusis has
      been blamed for being the most frequent cause of hearing loss in the elderly,
      causing verbal communication impairment. International studies also show the high
      prevalence of hearing loss in the elderly. DISCUSSION: According to recent
      investigations, as the number of elderly people increase, the prevalence of
      presbycusis interfering in the life quality of this population also increases.
      Even among health care professionals, there is a huge lack of knowledge about the
      advantages and gains a specific hearing reeducation can bring about for the
      elderly with hearing impairment. CONCLUSIONS: the papers hereby analyzed showed
      that the public health care centers with physicians and speech and hearing
      therapists, should establish the guidelines for the development of diagnostic
      programs, purchase of hearing aids and, most specially, hearing reeducation for
      the elderly with presbycusis, so that they may enjoy their social relations, and
      thus enhance their life quality. However, in Brazil, studies and research in this
      area only beginning.

PMID- 17505612
TI  - Adenomatoid odontogenic tumour associated with dentigerous cyst--unusual case
      report.
AB  - The adenomatoid odontogenic tumor is a relatively uncommon lesion which mainly
      affects females in their second decade of life, exhibiting predilection for the
      anterior region of the maxilla. The lesion is usually associated with the crown
      of an enclosed tooth, most commonly the maxillary canine. In this paper we
      present a case of adenomatoid odontogenic tumor associated with a dentigerous
      cyst affecting the left maxillary region in a 13-year-old female. The authors
      also discuss clinical, radiographic, histopathologic and therapeutic features of
      the case.

PMID- 17505613
TI  - Cheilitis granulomatosa associated with Melkersson-Rosenthal syndrome.
AB  - Melkersson-Rosenthal syndrome (MRS) consists of persistent or recurrent orofacial
      edema, relapsing facial palsy and fissured tongue. The complete triad of symptoms
      is uncommon, varying from 8 to 25%. The presentation of only one symptom is more
      common. The most frequent complaint is facial edema and enlargement of the lips.
      We describe a case of a 17-year-old Brazilian girl with limited edema of the
      lower lip and fissured tongue due to MRS. Her complaints had started two years
      before. She referred previous clinical treatments without success. We proposed
      intralesional injection of triamcinolone at 20 mg every 15 days associated with
      oral clofazimine at 50 mg/day for three months. The lip became normal after four
      triamcinolone injections. Recent studies have considered MRS a granulomatous
      disease, and possibly the initial presentation of Crohn's disease in orofacial
      area of some patients. MRS patients, therefore, should be screened and monitored
      for gastrointestinal symptoms. Corticosteroid treatment seems to be effective in
      reducing lip enlargement. We discuss the clinical features of this disease, the
      treatment, and the importance of corticosteroid therapy in cases of MRS-related
      facial palsy.

PMID- 17505614
TI  - Malignant otitis externa.

PMID- 17505615
TI  - Hereditary hemorrhagic telangiectasia: a new surgical approach.

PMID- 17505616
TI  - Peripheral primitive neuroectodermal tumor: a rare case of peripheral facial
      paralysis.

PMID- 17505617
TI  - Tympanic paraganglioma: two cases.

PMID- 17505618
TI  - Vocal fold paralysis in subacute thyroiditis.

PMID- 17505620
TI  - [Cardiovascular disease and diabetes].

PMID- 17505621
TI  - Adiponectin gene and cardiovascular risk in type 2 diabetic patients: a review of
      evidences.
AB  - Diabetic patients have a 3-fold higher risk of developing atherosclerosis and its
      clinical complications as compared to non-diabetic individuals. Part of the
      cardiovascular risk associated with diabetes is probably due to genetic
      determinants influencing both glucose homeostasis and the development of
      atherosclerosis. However, type 2 diabetes frequently coexists with other
      cardiovascular risk factors like arterial hypertension, central obesity and
      dyslipidemia. Genetic variability affecting many areas such as lipid and energy
      metabolisms, hypertension and haemodynamic mechanisms, blood clotting
      homeostasis, inflammation, and matrix turnover in the vascular wall will have an
      impact on the development of macrovascular complications in diabetic patients.
      Adiponectin is abundantly secreted by adipocytes. It plays important roles in
      lipid and glucose metabolisms and has direct anti-inflammatory and anti
      atherogenic effects. In this review, we summarize recent data from the literature
      suggesting an implication of allelic variations of the adiponectin gene (ADIPOQ)
      in the genetic determinants of cardiovascular disease in diabetic subjects.

PMID- 17505622
TI  - [Diabetic cardiomyopathy].
AB  - Diabetic cardiomyopathy is a myocardial disease caused by diabetes mellitus
      unrelated to vascular and valvular pathology or systemic arterial hypertension.
      Clinical and experimental studies have shown that diabetes mellitus causes
      myocardial hypertrophy, necrosis, and apoptosis, and increases interstitial
      tissue. The pathophysiology of diabetic cardiomyopathy is incompletely
      understood. It appears that metabolic perturbations such as hyperlipidemia,
      hyperinsulinemia, hyperglycemia, and changes in cardiac metabolism are involved
      in cellular consequences leading to increased oxidative stress, interstitial
      fibrosis, myocyte death, and altered intracellular ions transient and calcium
      homeostasis. Clinically, an early detection of asymptomatic diastolic dysfunction
      is possible. When patients develop signals and symptoms of heart failure,
      isolated diastolic dysfunction is usually detected. Systolic dysfunction is a
      late finding. Treatment of heart failure due to diabetic cardiomyopathy is not
      different from myocardiopathies of other etiologies and must follow the
      guidelines according to ventricular function, whether diastolic or diastolic and
      systolic impairment.

PMID- 17505623
TI  - Left ventricle diastolic dysfunction in diabetes: an update.
AB  - Diabetes mellitus, a disease that has been reaching epidemic proportions, is an
      important risk factor to the development of cardiovascular complication. Diabetes
      causes changes within the cardiac structure and function, even in the absence of
      atherosclerotic disease. The left ventricular diastolic dysfunction (VE)
      represents the earliest pre-clinical manifestation of diabetic cardiomyopathy,
      preceding the systolic dysfunction and being able to evolve to symptomatic heart
      failure. The doppler echocardiography has emerged as an important noninvasive
      diagnostic tool, providing reliable data in the stages of diastolic function, as
      well as for systolic function. With the advent of recent echocardiographic
      techniques, such as tissue Doppler and color M-mode, the accuracy in identifying
      the moderate diastolic dysfunction, the pseudonormal pattern, has significantly
      improved. Due to cardio-metabolic repercussions of DM, a detailed evaluation of
      cardiovascular function in diabetic patients is important, and some alterations
      may be seen even in patients with gestational diabetes.

PMID- 17505624
TI  - [Modifications of structural and functional properties of large arteries in
      diabetes mellitus].
AB  - Functional and structural modifications in large arteries play an important role
      in the pathogenesis of cardiovascular diseases. The diabetes mellitus besides
      arterial hypertension and ageing can induce these alterations in different
      arterial sites, and so leading to the development of atherosclerosis and its
      cardiovascular consequences. The main functional change of large arteries is an
      increase of stiffness, while the main structural modification is an increase of
      the intima-media thickness of carotid artery, and both changes have been
      recognized in both type 1 and type 2 diabetes. The mechanisms of these structural
      and functional arterial modifications in diabetes include insulin resistance,
      collagen increase due to inadequate enzymatic glycation, endothelial and
      autonomic dysfunction. The increase of arterial stiffness is an independent
      cardiovascular risk marker in diabetic patients, and the treatment of diabetes
      per se and even of associated dyslipidemia and arterial hypertension can
      favorably modify these arterial changes.

PMID- 17505625
TI  - [Cardiovascular autonomic dysfunction in experimental diabetes mellitus].
AB  - Much new information has been published in the last few years regarding
      pathophysiology of cardiovascular autonomic dysfunction in diabetic rats and
      mice. Our group has been studying the time-course cardiovascular changes
      associated with experimental diabetes in the last years, and obtained consistent
      evidences of severe dysautonomia in diabetes animal models. The aim of this
      manuscript is to review the contribution that studies involving different animal
      models of insulin deficiency or resistance have given to understand, treat and
      prevent diabetic cardiovascular autonomic dysfunction.

PMID- 17505626
TI  - [Insulin and angiotensin II signaling pathways cross-talk: implications with the
      association between diabetes mellitus, arterial hypertension and cardiovascular
      disease].
AB  - Insulin (Ins) and angiotensin II (AII) play pivotal roles in the control of two
      vital and closely related systems: the metabolic and the circulatory,
      respectively. A failure in the proper action of each of these hormones results,
      to a variable degree, in the development of two highly prevalent and commonly
      overlapping diseases--diabetes mellitus (DM) and hypertension (AH). In recent
      years, a series of studies has revealed a tight connection between the signal
      transduction pathways that mediate Ins and AII actions in target tissues. This
      molecular cross-talk occurs at multiple levels and plays an important role in
      phenomena that range from the action of anti-hypertensive drugs to cardiac
      hypertrophy and energy acquisition by the heart. At the extracellular level, the
      angiotensin-converting enzyme controls AII synthesis but also interferes with Ins
      signaling through the proper regulation of AII and the accumulation of
      bradykinin. At an early intracellular level, AII, acting through JAK-2/IRS-1/PI3
      kinase, JNK and ERK, may induce the serine phosphorylation and inhibition of key
      elements of the Ins-signaling pathway. Finally, by inducing the expression of the
      regulatory protein SOCS-3, AII may impose a late control on the Ins signal. This
      review will focus on the main advances obtained in this field and will discuss
      the implications of this molecular cross-talk in the common clinical association
      between DM and AH.

PMID- 17505628
TI  - Postprandial glycemia and cardiovascular disease in diabetes mellitus.
AB  - This article reviews the role of fasting and postprandial glycemia to the overall
      glycemic control of patients with type 2 diabetes and glucose intolerance, as
      well as their causal relationship upon micro and macrovascular complications.
      Recent studies have suggested that a third component of the glucose triad, the
      postprandial glucose excursions, might have a role in the overall glycemic load
      and might also reflect glycemic control. Epidemiological and intervention studies
      are presented in the article, supporting the conclusion that postprandial
      hyperglycemia in impaired glucose tolerance and diabetic subjects is a more
      powerful marker of cardiovascular disease risk than fasting hyperglycemia, then
      the treatment directed at specifically lowering postprandial glucose is crucial,
      as underlined by the American Diabetes Association.

PMID- 17505627
TI  - [Microcirculation in diabetes: implications for chronic complications and
      treatment of the disease].
AB  - Diabetic microangiopathy is responsible for an important rate of morbidity and
      mortality related to the disease. Endothelial damage seems to be the triggering
      factor in the pathogenesis of microvascular complications. Diabetes mellitus and
      other metabolic diseases are associated to endothelial dysfunction, the most
      precocious known marker of atherosclerosis. Changes on microvascular reactivity
      are present in patients with diabetes mellitus, as well as in individuals with
      risk factors for this disease. Evaluation of endothelial and microvascular
      functions is possible using different invasive or preferentially non-invasive
      methods. Adequate control of diabetes mellitus might postpone or perhaps even
      prevent the microvascular disease. Microvascular dysfunction, when seen only by
      changes on microvascular reactivity, could be ameliorated with correction of risk
      factors or drug treatment.

PMID- 17505629
TI  - [The role of post-prandial lipids in atherogenesis: particularities of diabetes
      mellitus].
AB  - Atherosclerosis is a complex and multifactorial disease, which determines
      clinical events that cause significant morbidity-mortality, represented by acute
      myocardial infarction, angina and sudden death. It is associated with lipid
      disturbances, platelet activation, thrombosis, endothelial dysfunction,
      inflammation, oxidative stress, altered matrix metabolism, among other
      disturbances. All these abnormalities are usual and more pronounced in diabetic
      patients, as well as in the post-prandial state. Among the coronary artery
      disease risk factors that are not usually employed in clinical practice in the
      whole population, postprandial hyperlipemia plays a major role, being a possible
      early marker of metabolic abnormalities and vascular dysfunction not yet seen in
      the fasting state. Recent results showed that post-oral lipid overload changes
      are negatively associated with endothelial dysfunction, and vascular reactivity
      abnormalities are strongly related to atherosclerosis progression and
      cardiovascular events. These abnormalities could disclose a lipid intolerance
      state that can be detected in apparently healthy subjects even before fasting
      abnormalities are seen. This review will deal with the pathophysiology changes
      involved in post-prandial hyperlipemia and its relationship with atherogenesis,
      with particular emphasis to diabetes mellitus.

PMID- 17505630
TI  - [Cardiovascular impact of the autonomic neuropathy of diabetes mellitus].
AB  - The neuropathic complications related to Diabetes may affect the somatic,
      sympathetic and parasympathetic nervous system. As a result, there are several
      clinical manifestations of diabetic neuropathy. They can be related to nervous
      system lesions of the genital, urinary, gastro-intestinal, skin and
      cardiovascular tissues. The results of these alterations are loss in the quality
      of life as well as increase of mortality indexes related to sudden death with
      cardiac arrhythmias and other causes. The cardiovascular autonomic neuropathy
      probably contributes to the bad prognosis of the coronary heart disease and of
      the heart failure in type 1 and type 2 diabetic patients. For diabetologists, the
      nervous complications of diabetes are the result of an increase influx of glucose
      to the neuronal and endothelial cells. Evidences show that, with the aim of
      preventing these complications, the diabetic patients should receive a precocious
      diagnosis and be instructed for having a good metabolic and blood pressure
      control. Use of angiotensin converting enzyme inhibitors and beta adrenergic
      blockers are probably of impact in the prevention of the cardiac autonomic
      complications of diabetes.

PMID- 17505631
TI  - [Diabetic nephropathy and cardiac disease].
AB  - Patients in different stages of diabetic nephropathy (DN) frequently present
      cardiac disease expressed by myocardial ischemia and/or diabetic cardiomyopathy.
      These changes are already present at early stages of DN, probably even before
      urinary albumin excretion (UAE) reaches the traditionally diagnostic levels of
      microalbuminuria. The cardiac changes are responsible for a significant
      proportion of the increased death rates in patients with DN and can be reduced
      through multiple intervention on the several risk factors present in these
      patients. Cardiac disease assessment should ideally be performed in every
      patient, irrespective of renal status, through specific methods to detect
      ischemia and myocardial dysfunction, besides routinely performing 24-h ambulatory
      blood pressure monitoring. In patients with advanced atherosclerosis, other
      arteries (aorta, carotid, renal) should be evaluated as well. Intensive treatment
      of arterial hypertension, and use of cardioprotective drugs, correction of the
      associated dyslipidemia and anemia, and use of antiplatelet agents can reduce the
      elevated cardiovascular mortality in patients with DN.

PMID- 17505632
TI  - [Cardiovascular disease in diabetes mellitus: classical and non-classical risk
      factors].
AB  - Cardiovascular disease, which includes coronary heart disease (CHD),
      cerebrovascular disease (CVD), and peripheral vascular disease (PVD), is the
      leading cause of mortality in populations, particularly in the diabetic one.
      Individuals with diabetes have at least a two-fold to four-fold increased risk of
      having cardiovascular events and a double risk of death compared with age-matched
      subjects without diabetes. A decline in mortality from CVD has been shown, but
      decline due to CHD is consistently lower in individuals with diabetes when
      compared with non-diabetics. The presence of several factors in diabetes leads to
      high occurrence of CVD such as hyperglycemia, insulin resistance, and classical
      and non-classical risk factors (systemic hypertension, dyslipidemia, obesity,
      proinflammatory condition and others). It is possible that the atherogenic role
      of obesity may be at least in part due to increased adipocyte production of
      cytokines. Considering the marked association of diabetes and CVD and unfavorable
      prognosis following an event, it is important to identify who is at high risk and
      how to screen. The American Heart Association and American Diabetes Association
      recommend risk stratification using diagnostic tests. However, the challenge is
      to accurately identify patients without a prior history of an event and those
      without symptoms strongly suggesting CVD, in whom additional testing would be
      indicated in order to achieve the most effective prevention. The benefits of
      glycemic control and the other risk factors have already been shown and justify
      optimization of the management of this high-risk population, aiming to reduce
      cardiovascular mortality disease and improve quality of life.

PMID- 17505633
TI  - [Evaluation of cardiovascular risk according to Framingham criteria in patients
      with type 2 diabetes].
AB  - OBJECTIVE: The aim of our study was to evaluate cardiovascular risk (CR) in type
      2 diabetic (T2DM) patients according to Framingham criteria and its possible
      relationship with other risk factors not included in the Framingham score.
      PATIENTS AND METHODS: We evaluated 333 T2DM outpatients (215 females), aged
      56.9+/-9.7 years followed regularly from March 2004 to February 2005 in the
      Diabetes Unit in our University Hospital. The known diabetes duration was 12 (0
      43) years. In order to determinate the risk of death from coronary artery disease
      (CAD), we applied the Framingham score. Patients were classified in two groups,
      according to their probability of having a cardiovascular event in ten years:
      <or=20% and>20%. We intended to establish a correlation between the CR verified
      in this population and other variables probably related to CR not included on
      Framingham score. RESULTS: The CR in ten years was 18.7+/-10.8% in the whole
      population, being higher in male than female [20% (2-53) vs. 15% (1-27);
      p<0.001]. Fifty five percent of males and 38.6% of females had a CR>20% according
      to Framingham score (p=0.003). The CR was related to diabetes duration,
      triglycerides (TG), creatinine and 2-hour postprandial plasma glucose (2G) levels
      and abdominal circumference (AC) either according to International Diabetes
      Federation (p<0.001) or World Health Organization (p=0.003) criteria. In the
      stepwise multivariate analyses we found an independent and significant
      correlation of CR with the following variables: gender (male), diabetes duration,
      plasma creatinine levels, AC and TG (p<0.001). CONCLUSION: Our T2DM patients
      represent a high-risk population for cardiovascular events according to the
      Framingham score, mainly males. Routine use of Framingham score, which is
      feasible and noninvasive, could identify such patients and institute precocious
      and intensive measures in order to reduce their cardiovascular risk.

PMID- 17505634
TI  - [The impact of diabetes mellitus on the mortality of acute coronary syndromes].
AB  - Diabetes mellitus (DM) is a leading cause of mortality in the world, mainly on
      account of cardiovascular diseases. At present we know that not only DM but also
      other hyperglycemic states are a risk factor for coronary arterial disease. In
      the context of acute coronary syndromes, DM determines a worst prognosis, either
      in short- or long-term outcomes. Since the absolute risk of death is greater
      among diabetic patients when compared to non-diabetic patients, therapeutical
      interventions have a greater impact in terms of benefits to these patients as
      well. Strategies such as strict control of hyperglycemia during hospitalization,
      acute reperfusion management (either by thrombolysis or by percutaneous coronary
      intervention), use of platelet glycoprotein IIb/IIIa inhibitors and angiotensin
      converting enzyme (ACE)-inhibitors have recently proven to be of greater benefit
      for diabetics over non-diabetic patients. Meanwhile, in spite of all proven
      benefits of the use of evidence-based interventions to the treatment of acute
      coronary syndromes on diabetic patients, there is still an under utilization of
      these measures. Therefore, taking into account the predictions of an increasing
      number of diabetics in the world for the future years, and the fact that acute
      coronary syndromes will be the leading cause of death among them, it becomes
      increasingly necessary for both cardiologists and endocrinologists to work
      together in order to reduce the unfavorable outcomes that are expected to arise.

PMID- 17505635
TI  - [Cardiovascular assessment of diabetic patients].
AB  - INTRODUCTION: Type 2 diabetes is a cardiovascular disease. The morbidity and
      mortality among these patients are primarily due to cardiovascular diseases.
      There are many guidelines regarding clinical evaluation of cardiovascular disease
      in those patients. Implementation of these guidelines has been an argued subject.
      Our objective in this paper is to describe what basal cardiovascular evaluation
      has been carried out at a specialized university Diabetes Center. SUBJECTS AND
      METHODS: Data were collected from February to October 2006 of 121 type 2 diabetes
      individuals who were enrolled at the Diabetes Center of Federal University of Sao
      Paulo. We analyzed the type of cardiovascular disease evaluation that they had
      been submitted in the year that preceded the consultation. RESULTS: We have
      observed a high prevalence of several other cardiovascular risk factors in this
      population. The cardiovascular evaluations during this period has shown 36% of
      the patients had not been submitted to any cardiovascular test, 17% had been
      submitted to resting electrocardiogram and 27% of the patients had been submitted
      to exercise test. Rest echocardiogram, pharmacologic stress echocardiogram,
      myocardial perfusion scintigraphy, and coronary angiography have been carried out
      in a much lesser ratio. CONCLUSION: Our data has shown the variability and
      limitations on boarding diagnosing of DAC in university environment patients and
      point us the necessity of constructing defined and directed directives for the
      peculiarities of the Brazilian population and health system.

PMID- 17505636
TI  - Silent myocardial ischemia screening in patients with diabetes mellitus.
AB  - The prevalence of diabetes mellitus is fairly increasing, especially in the
      developing countries. Diabetes is a major cardiovascular risk factor; it often
      leads to severe cardiovascular complications, and coronary artery disease (CAD)
      is the main cause of death in diabetic patients. Silent myocardial ischemia (SMI)
      is more frequent in diabetic patients. The progress made in detection and
      treatment of CAD allows reconsidering the screening of SMI, in the hope that
      early CAD diagnosis leads to a more effective therapy and the decrease of
      cardiovascular complications and mortality. However, the benefit of systematic
      SMI screening remains discussed. Current guidelines recommend screening SMI in
      asymptomatic diabetic patients selected for high cardiovascular risk (i.e. with
      two or more other cardiovascular risk factors, or peripheral or carotid arterial
      disease, or proteinuria). ECG stress test can be recommended in first intention
      if maximal heart rate can be achieved. For patient with inconclusive ECG stress
      test, myocardial scintigraphy seems more accurate than stress echocardiography.
      Coronary angiogram should be performed in case of positive stress test. Further
      evaluations of systematic screening have to be conducted on broad randomized
      trial.

PMID- 17505637
TI  - [Calcium score in the cardiovascular evaluation of the diabetic patient].
AB  - Coronary artery calcium (CAC) is a specific marker of atherosclerosis,
      independent of its etiology. Quantification of CAC by computed tomography (CT) is
      a non-invasive test recommended mainly for risk stratification for coronary heart
      disease, in addition to the conventional stratification, especially in
      intermediate risk patients. Currently, a diabetic patient is classified as a
      coronary heart disease equivalent, therefore a high-risk patient according to
      most societies. For that matter calcium score is not currently recommended for
      diabetic patients. Although quantification of CAC by computed tomography (CT) is
      not yet supported by strong evidence in diabetes, small studies showed evidence
      that this test could have a discriminatory power in terms of prognosis within
      this group of patients. That could be a future clinical application, depending on
      the validation of these data and the results of future studies. There are some
      other potential applications for this method that could be useful for diabetic
      patients as well, but haven't been extensively validated, like the assessment of
      progression of coronary artery calcium as a form of evaluating effectiveness of
      medical therapy. In this article we review the method and current indications for
      the quantification of CAC by computed tomography.

PMID- 17505638
TI  - [Coronary angiography and angioplasty in diabetic patients].
AB  - Screening, diagnosis and revascularization of coronary artery disease (CAD) in
      type 2 diabetes mellitus are major challenges for current clinical practice.
      Diagnostic (angiography) and therapeutic (angioplasty) cardiac catheterization
      are important resources for the clinical assessment and management of coronary
      atherosclerosis. Anatomic peculiarities of CAD in diabetics can be well
      characterized by angiography, associated or not by intravascular ultrasound. The
      worse outcome following coronary revascularization procedures, either angioplasty
      or surgery, in diabetic is one of the main fields of clinical research. In spite
      of controversies, about one quarter of angioplasty and one third of surgical
      revascularization procedures are performed in diabetics. Two ongoing, large,
      randomized, multicentric trials are investigating the best management of CAD in
      diabetics. The BARI 2D trial is randomizing asymptomatic or mildly symptomatic
      patients with CAD for either medical therapy or revascularization (angioplasty or
      surgery, according to the best clinical judgment). The FREEDOM trial is
      randomizing stable patients with multivessel CAD for either angioplasty with drug
      eluting stents or surgery, with or without extracorporeal circulation. While the
      evidences are not available, in order to decide on the best revascularization
      procedure for individual patients, medical practice has been balanced according
      to a number of variables. Conditions that favor angioplasty: short lesions,
      lesions in large vessels, absence of left anterior descending artery disease,
      previous coronary bypass surgery and high surgical risk due to co-morbidities.
      Conditions that favor surgery: long lesions, lesions in small vessels, presence
      of left anterior descending artery disease and need for associated valve surgery.

PMID- 17505639
TI  - [Cardiovascular disease in diabetic women without cardiac symptoms].
AB  - Cardiovascular disease is the main cause of cardiac death among diabetic
      patients. The myocardial ischemia is frequently asymptomatic, leading to late
      diagnosis and making prognosis worse. This is particularly true for women, for
      whom this diagnostic is possibility often disregarded. Appropriate screening can
      modify the coronary artery disease risk. The early diagnosis is highly
      beneficial, particularly regarding females. The decision of which non-invasive
      diagnostic method should be used in the initial evaluation is difficult. There
      are several diagnostic methods to make the preliminary investigation of coronary
      artery disease in diabetic women even without cardiac symptoms, but there is
      still no consensus about who should be investigated and when should the first
      cardiac evaluation start. The prevalence of the disease, as well as the cardiac
      risk, must be known in order to justify a broad survey, mainly in the female
      population.

PMID- 17505640
TI  - [Cardiovascular prevention in diabetic patients: an evidenced-based review].
AB  - Diabetes mellitus is a condition associated with cardiac complications,
      especially artherothrombotic disease. Several studies have demonstrated the
      importance of reducing cardiovascular burden on this population by adopting
      prevention strategies. This article revised clinical evidences on cardiovascular
      risk assessment and prevention actions, taking into consideration major
      recommendations in the field. Life-style changes with low-carbohydrate diet,
      weight control, and regular physical activity must be implemented. High-risk
      patients or with established cardiovascular disease ought to have glycemic
      levels<100 mg/dL and A1c<7%. It is recommended low dose of aspirin and statin for
      lipid management, targeting LDL<100 mg/dL, HDL>50 mg/dL and tryglycerides<150
      mg/dL. Blood pressure control with non-pharmacological and antihypertensive drugs
      must be instituted, favoring ACE inhibitors as first option, mainly in patients
      with renal disease, and combined with tiazydes for the majority to achieve target
      blood pressure of <130/80 mmHg.

PMID- 17505641
TI  - [State-of-the-art in the treatment of chronic coronariopathy in diabetic
      patients: evidences and controversies based in clinical trials].
AB  - Diabetes mellitus is a powerful risk factor for coronary artery disease.
      Diabetics demonstrate accelerated coronary atherosclerosis and worst prognosis
      following cardiac events. Although myocardial revascularization procedures result
      in more effective relieve of symptoms in patients with known coronary artery
      disease, there is no substantial evidence that this strategy improves outcome,
      except for specific situations. In addition, the benefit of myocardial
      revascularization is attenuated by the presence of metabolic abnormalities
      related to insulin resistance and other significant co-morbidities in diabetic
      patients. New advances recently developed for the clinical treatment of diabetes,
      as well as surgical and percutaneous approaches of myocardial revascularization,
      such as drug-eluting stents, seem to be promising therapeutical strategies for
      diabetic patients. Most importantly, treatment of type 2 diabetics with chronic
      coronary artery disease should consider the multifactorial pathogenesis of the
      disease and combine aggressive control of glycemic levels, strict management of
      all conventional risk factors, and lifestyle modification. The metabolic effects
      of insulin sensitizers over cardiovascular disease and mortality are under
      discussion. Ongoing clinical multicenter trials will probably define the real
      impact of new therapeutic modalities over the prognosis of diabetic patients.

PMID- 17505642
TI  - [Percutaneous coronary intervention in diabetes mellitus: an updated analysis of
      medical practice].
AB  - Patients with diabetes and coronary artery disease are frequently considered for
      myocardial revascularization procedures, aiming at cardiovascular events risk
      reduction and a better quality of life. In clinical practice, decisions
      concerning surgery or percutaneous coronary intervention are frequently
      difficult, because of cases' severity, disease extension and co-morbidities
      association. Beyond that, the bulk of literature information was generated by
      subgroup analysis of randomized clinical trials, which were designed for the
      general population, not for diabetics. The aim of this study was to review
      literature on coronary percutaneous intervention in diabetic patients, and also
      to show recent data from the experience in this procedure at the Catheterization
      Laboratory of the Cardiology Institute of RS.

PMID- 17505643
TI  - [Adjuvant drug treatment in diabetic patients undergoing percutaneous coronary
      intervention].
AB  - The authors describe the adjuvant drug treatment during and after percutaneous
      coronary intervention in order to obtain the reduction of major cardiovascular
      events, focusing in diabetic patients. In the clinical follow-up of diabetic
      patients after PCI, special attention to the control measures of cardiovascular
      risk factors should be observed. Among those measures, a normal glycemic level is
      fundamental, which can be achieved with usual clinical care. Antiplatelet therapy
      is a controversy issue until know. Although combined antiplatelet therapy with
      aspirin and a thienopyridynic is well supported by a number of clinical trials,
      adding GPIIb/IIIa agents as adjuvants in diabetic patients should not be
      irrestrictive as suggested by some authors; they should be restricted to patients
      with a significative thrombotic burden.

PMID- 17505644
TI  - [Coronary artery surgery in patients with diabetes mellitus].
AB  - Diabetes mellitus is present in 25-30% of patients undergoing coronary artery
      bypass grafts surgery. Early and late post-operative prognoses are different for
      the diabetic patient. Coronary artery bypass grafts are indicated in 2 or more
      vessel lesions, but it can also be preferred to percutaneous angioplasty in 1
      vessel lesions, when this is the anterior descending artery or there is a great
      area under ischemia. Diabetic candidates to renal transplant must be investigated
      and revascularized pre-operatively, if necessary. Morbidity is greater in these
      patients, mainly due to respiratory, renal and cerebral complications and wound
      infections. Intensive care unit and hospital length of stay are more prolonged,
      but there is not increased early mortality. Diabetes mellitus represents an
      independent risk factor for late graft failure and mortality from cardiac and
      general causes. Although under an increased risk, coronary artery surgery results
      in better quality of life and late survival in the diabetic patients with severe
      coronary artery disease, as compared to medical treatment and percutaneous
      coronary angioplasty, specially in those who use insulin and when internal
      thoracic arterial grafts are implanted.

PMID- 17505645
TI  - Retinal vascular signs in diabetes and hypertension--review.
AB  - The retinal vasculature is a unique site where the microcirculation can be
      noninvasively imaged in vivo. This presents an opportunity to study otherwise
      inaccessible structural features of the microcirculation. Recently, a number of
      population-based studies have developed quantitative methods of measuring these
      retinal signs, and investigated how these signs relate to metabolic disorders
      such as diabetes, hypertension, obesity, and metabolic syndrome. These studies
      have reported fairly consistent associations of retinopathy lesions, arteriolar
      narrowing and venular dilation with these metabolic disorders, suggesting a
      microvascular component in either the pathogenesis or manifestation of these
      disorders. Further, several of these signs have been associated with future risk
      of cardiovascular outcomes, such as coronary heart disease and stroke,
      independently of traditional risk factors. This review will examine in detail the
      evidence linking retinal vascular signs with metabolic disorders and discuss
      their implications for research and clinical practice.

PMID- 17505647
TI  - Effects of hyperglycemia and aging in angiogenesis and reepithelization of
      colonic anastomoses in rats.
AB  - PURPOSE: To evaluate angiogenesis and reepithelization of colonic anastomoses in
      rats. METHODS: 82 Wistar rats, divided into: young normoglycemic, old
      normoglycemic and hyperglycemic. Diabetes was induced with streptozotocin.
      Glycemia was assessed before induction, at 24 hours and after 90 days, when a
      colotomy and an anastomosis were performed, assessed at days 3, 7, and 14.
      Samples were prepared by immuno-histochemistry (PCNA and antifactor VIII).
      RESULTS: Mean glycemia after 90 days streptozotocin induction was 244,95 mg/dl.
      Day 7, reepithelization was greater in the young group than in the old
      normoglycemic (p<0.0001) and old hyperglycemic (p<0.0001) groups. Day 14, the
      differences were significant between the young and old normoglycemic (p<0.0001)
      and old hyperglycemic (p<0.0001) groups. The two old groups were not
      significantly different. At the three periods angiogenesis was higher in the
      young group than in the old normoglycemic (p3=0.014; p7<0.0001; p14<0.0001) or
      the old hyperglycemic groups (p3=0.014, p7<0.0001; p14<0.0001). The old groups,
      day 3, were not different (p3=0.627), but days 7 and 14, angiogenesis was bigger
      in the normoglycemic group (p7=0.042; p14=0.005). CONCLUSION: Age is important in
      reepithelization and angiogenesis of colonic anastomoses. Hyperglycemia
      interferes mainly in angiogenesis.

PMID- 17505648
TI  - Evaluation of the macroscopic growth degree of experimental endometriosis in
      rats.
AB  - PURPOSE: To evaluate macroscopically the growth degree of self-transplantation of
      endometriosis in rats. METHODS: Forty female rats, after a 7-day period for
      adpating and evaluating of the estrous cycle regularity, underwent tail abdominal
      midline laparotomy with 3-cm cuts. The average third of the left uterine horn was
      removed, 4mm x 4mm patches in liquid environment were made, and self-transplanted
      in the rat mesenterium with a single stitch, and the endometrial surface of the
      endometriotic implant facing the lumen of the peritoneal cavity. The rats were
      programmed to die after three weeks. The abdominal cavity displaying was held and
      self-transplants were identified and classified. RESULTS: The results achieved
      were: one case for degree 0 (2,5%), three cases for degree 1 (7,5%), eleven cases
      for degree II (27,5%) and twenty-five cases for degree III (62,5%). CONCLUSION:
      The experimental endometriosis development, through the self-transplantation
      technique, showed to be most common in degrees 3 and 2 of development.

PMID- 17505649
TI  - Healing of abdominal wall aponeurosis of rats after incision with either cold
      scalpel or electrocautery.
AB  - PURPOSE: To compare the healing of abdominal wall aponeurosis of rats after
      incision with either cold scalpel or electrocautery. METHODS: Twelve male adults
      Wistar inbred rats weighing 258-362g entered the experiment. They were randomly
      divided in two groups, control group (N= 6) and experimental group (N= 6). All
      animals underwent anesthesia followed abdominal wall incision with either cold
      scalpel (controls) or electrocautery (experimental group). The animals were
      killed on the 10th day and necropsied. Tissue samples containing the abdominal
      wall aponeurosis were sent for both histological study and hydroxyproline content
      assay. RESULTS: The histological study showed no significant difference between
      the two groups. Hydroxyproline content in experimental group (128,56 [78,98
      198,92] microg /100 m) was not significantly different from control group (140,27
      [116,20-166,59] mg /100 ml; p = 0.53). CONCLUSION: Healing of abdominal wall
      after dieresis with either cold scalpel or electrocautery are equivalent and do
      not differ.

PMID- 17505650
TI  - Experimental model of pulmonary carcinogenesis in Wistar rats.
AB  - PURPOSE: To elaborate an experimental model of pulmonary carcinogenesis in Wistar
      rats. METHODS: Male Rattus norvegicus albinus, Wistar lineage were carried
      through an intra-pulmonary instillation of the Benzo[a]pyrene (B[a]P) dilution in
      alcohol 70%, a polycyclic aromatic hydrocarbon widely known by its power of
      tumoral induction. Three experimental groups had been formed with 08 animals
      each: Control Group (Alcohol 70%); B[a]P Group 10 mg/kg; e B[a]P Group 20mg/kg,
      submitted to euthanasia 08, 10, 12 and 14 weeks after the experimental procedure.
      The pulmonary sections had been colored by hematoxilin-eosin (HE) and submitted
      to the morphometrical analysis to describe the tissue alterations. RESULTS: The
      presence of diffuse inflammatory alterations was observed in all groups; however,
      at the analysis of the pulmonary tissue of the experimental groups had been
      observed hyperplasic alterations (BALT hyperplasia), and in one of the animals of
      the experimental group 20mg/kg (12 weeks) was noticed the presence of cellular
      epithelial tracheal pleomorphism, suggesting the adenocarcinoma formation in
      situ. CONCLUSION: The main secondary alterations to the intra-pulmonary
      instillation of B[a]P in Wistar rats were: cellular proliferation, inflammatory
      alterations of several degrees and nodular lymphoid hyperplasias. The association
      of an activator agent of the pulmonary metabolic reply is necessary to establish
      the ideal reply-dose to the development of the lung cancer.

PMID- 17505651
TI  - Preservative spleen surgery and hyperbaric oxygen therapy.
AB  - PURPOSE: To assess functional and morphological aspects of spleen auto-implants
      and of the splenic inferior pole of rats, post-operatively treated or not with
      hyperbaric oxygen, as well as the survival of these animals, were studied.
      METHODS: Seventy-eight male Wistar rats, weighing between 192 and 283 g ( 238,3
      +/- 9,6g), were randomly distributed into three groups: Group 1--(n=20), spleen
      manipulation; group 2--(n=36), spleen auto-implantation; group 3--(n= 22),
      subtotal splenectomy preserving the inferior pole. Each group was subdivided as
      follows: subgroup a, not submitted to hyperbaric oxygen therapy: 1a(n=10),
      2a(n=21), 3a(n= 13); subgroup b, submitted to the therapy: 1b(n=10), 2b(n=15),
      3b(n=9). Blood was collected pre-operatively and 11 days after surgery, for the
      estimation of lipids and immunoglobulins and the counting of platelets and Howell
      Jolly corpuscles. The spleen and remains were taken for histological study.
      RESULTS: The number of surviving animals was significantly higher in groups
      1(p<0,01) and 3(p<0,05) relative to those of subgroup 2a. Total cholesterol and
      the LDL fraction increased significantly in subgroup 2a (p<0,01) and 3a (p<0,05),
      and remained unaltered in subgroups 2b e 3b. IgM decreased more significantly in
      subgroup 2 than in subgroup 3 (p<0,001 vs p<0,01). The increase of platelet
      numbers and the appearance of Howell Jolly corpuscles was smaller in subgroup 2b
      compared to subgroup 2a , and in group 3 compared to group aqui-> 2. The macro
      and microscopic appearance in subgroup 2b were more viable than in subgroup 2a,
      and that of group 3 more viable than in group 2. The survival of the animals
      carrying their whole spleen or its inferior pole was more frequent than that of
      the auto-implanted animals. CONCLUSION: Functionality and viability of the whole
      spleen or of its inferior pole, were better than in the auto-implanted animals.
      Hyperbaric oxygen-therapy contributed to increased survival frequency of auto
      implanted animals, and to improve the functionality and viability of the auto
      implants and the function of the inferior splenic pole, and did not interfere in
      animals carrying their whole spleen.

PMID- 17505652
TI  - Validity of microporous polysaccharide hemispheres as a hemostatic agent in
      hepatic injuries: an experimental study in rats.
AB  - INTRODUCTION: In the treatment of hepatic injuries, there is not always adequate
      and secure hemostasis. A hepatic biopsy is indispensable in the evolution of
      focal or diffuse liver cell disease, being necessary for candidates for liver
      transplant and post-transplant treatment. Many patients suffer blood clotting
      that increases the risk of bleeding. For this reason, it is necessary to seek for
      substances capable of bringing about hemostasis quickly and effectively. PURPOSE:
      The aim of this study was to recognize the validity of the use of microporous
      polysaccharide hemispheres (MPH) as a hemostatic agent for hepatic injuries.
      METHODS: Thirty Wistar rats were used, split into three groups. Under
      anaesthetic, a laparotomy was done and resulted in a standard liver injury that
      was treated in Group A with MPH, in Group B with n-butyl-2-cyanoacrylate and in
      Group C with fibrin adhesive. Immediate hemostasis, delayed bleeding and
      histological evolution were timed. RESULTS: The MPH took on average six minutes
      to promote hemostasis and also resulted in re-bleeding, which required
      reapplication; the n-butyl-2-cyanoacrylate took twenty seconds and the fibrin
      adhesive took one minute. The cyanoacrylate resulted in more intense adherence.
      The three adhesives mainly showed a chronic inflammatory reaction. The injuries
      treated with cyanoacrylate showed a larger area of injury (p=0,0164). The density
      of the collagen was similar in all groups. CONCLUSION: The MPH, despite achieving
      hemostasis, proved to be no more favorable than n-butyl-cyanoacrylate and the
      fibrin adhesive, the latter resulting in the lowest tissue reaction.

PMID- 17505653
TI  - The intestinal tract as the major source of interleukin 6 production during
      abdominal aortic clamping and hind limb ischaemia-reperfusion injury.
AB  - PURPOSE: The aim of this study was to investigate whether the hind limbs or
      intestinal tract is the most important initiator of the inflammatory response
      secondary aortic clamping and hind limb ischemia/reperfusion injury. METHODS:
      Blood samples of Wistar rats obtained from posterior cava vein, portal vein, and
      heart cavity during either laparotomy (control group, n=8) or laparotomy + 2 h of
      aortic clamping and bilateral hind limb ischemia (ischemia group, n=8), or 2 h
      after ischemia and 2 h of reperfusion (ischemia-reperfusion group, n=8) were
      assayed for interleukin 6 (IL-6) and C-reactive protein (CRP). RESULTS: Serum IL
      6 at the heart (223.6+/-197.9 [10-832] pg/mL) was higher (p<0.001) than at both
      portal (133.08+/-108.52 [4-372] pg/mL) and posterior cava veins (127.58+/-109.15
      [8-388] pg/mL). CRP was not significant different among groups. CONCLUSION: The
      splanchnic region is also a source of inflammatory response secondary to ischemia
      and reperfusion of the hind limbs.

PMID- 17505654
TI  - Effects of budesonide and probiotics enemas on the systemic inflammatory response
      of rats with experimental colitis.
AB  - PURPOSE: The aim of this study was to investigate the effect of enemas containing
      probiotics and budesonide on the systemic inflammatory response in experimental
      colitis. METHODS: Fifty male Wistar rats with experimental colitis induced by 10%
      acetic acid enema were randomized to five groups (10 rats each) according to the
      treatment: group 1--saline solution, group 2--budesonide (0.75 mg/kg/day), group
      3--probiotics (1mg/day), group 4--probiotics plus budesonide, and group 5-
      control, with not-treated rats. The following variables were studied: body
      weight, serum levels of albumin, C-reactive protein and interleucine-6 (IL-6).
      RESULTS: All animals lost weight between the beginning and the end of the
      experiment (280+ 16 mg versus 249+21 mg, p< 0.001). There was a significant
      decrease in the serum albumin between the normal pre-induction level (3.45 + 0.49
      mg/dL) and the 1st day after colitis induction (1.61+051 mg/dL, p< 0.001) in all
      treated groups when compared to the control group. C- reactive protein increased
      after induction and diminished on the 7th day in all groups. In the control group
      there was an increase in the IL-6 after colitis induction. None of the treated
      groups significantly differed from IL-6 pre-colitis status (p>0.05). Only
      probiotic rats presented a significant decrease of IL-6 than controls (0,30+/
      0,08 mg/dL vs. 0,19+/-0,03 mg/dL; p<0.01). CONCLUSION: Probiotics are effective
      to diminished inflammatory status mediated by IL-6 in experimental colitis.

PMID- 17505656
TI  - The influence of hypothyroidism on liver regeneration: an experimental study in
      rats.
AB  - BACKGROUND: The influence of hypothyroidism in liver regeneration has been a
      controversial opinions. PURPOSE: The aim of this study is to identify the
      relationship between hypothyroidism and liver regeneration in rats. METHODS:
      Forty male Wistar rats divided into two groups of 20 specimens each. One group
      (C) consisted of euthyroid rats, and the other (H) of hypothyroid rats. All the
      animals were anesthetized with xylazine and ketamine and subjected to a
      longitudinal incision in the anterior cervical region. The thyroid was completely
      resected in group H and left intact in group C. Ten days after the first surgery,
      both groups of rats were weighed and submitted to partial hepatectomy, in which
      the left lateral and median lobes were resected and weighed. Examinations were
      carried out after 24 hours and, on day 7, using 3 methods: KWON et al.'s formula
      to identify increase in volume; mitotic figure count in five fields; and the
      percentage of PCNA-positive nuclei in five fields. RESULTS: Using KWON's formula,
      the regeneration rate for Group C after 24 hours was 58.49% whereas that for
      Group H was 50.42% (p=0.0165). After 7 days, the regeneration rate for Group C
      was 93.04% and Group H 93.74% (p=0.2165). The average number of mitotic figures
      after 24 hours was 14 +/- 1.5 for Group C and 9.8 +/- 2.2 for Group H
      (p=0,00016). After 7 days the corresponding figures were 5.4 +/-1.1 and 5.1+/-
      1.2 (p=0,6343). The average number of PCNA-positive nuclei after 24 hours was
      13.55+/- 3.84 in Group C and 7.7 +/- 2.11 in Group H (p =0,0006)). The
      corresponding figures after 7 days were 3.5 +/- 2.39 for Group C and 4.11 +/-1.90
      for Group H (p>0.05). CONCLUSION: We conclude that hypothyroidism in rats causes
      a delay in hepatic regeneration in the first 24 hours, but that after seven days
      the rate of regeneration is equal to that in euthyroid rats.

PMID- 17505655
TI  - Lipidic profile among rats submitted to total splenectomy isolated or combined
      with splenic autotransplant.
AB  - PURPOSE: To evaluate the alterations on plasmatic lipids levels among rats
      submitted to total splenectomy isolated or combined with splenic autotransplant
      receiving standard chow during the postoperative period. METHODS: Thirty Wistar
      rats were divided into three groups: control (C)-- sham-operated, total
      splenectomy--isolated (TS) or combined with splenic autotransplantation (SA).
      Since the postoperative period, all animals received standard rat chow
      manipulated in accordance to the American Institute of Nutrition Rodents Diets
      (1993). The plasmatic levels of total cholesterol (TC), triglycerides (TG), high
      density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density
      lipoprotein (VLDL), and glucose (GLUC) were analyzed before the surgical
      procedure and after 6 and 12 weeks. RESULTS: All the animals presented
      significant increase of TG and VLDL levels. In relation to the other parameters
      there was no difference among the weeks 0 and 12 in the animals of group C. In TS
      group significant increase was observed in TC and GLUC levels during the
      experiment. In SA group TC, HDL, and GLUC levels remained unaffected while HDL
      levels increased. CONCLUSION: Our findings suggest that isolated total
      splenectomy alters lipids metabolism in rats fed with standard chow and splenic
      autotransplantation is effective in restoring its control.

PMID- 17505657
TI  - Simvastatin improves the healing of infected skin wounds of rats.
AB  - PURPOSE: This study explores the potential of the simvastatin to ameliorate
      inflammation and infection in open infected skin wounds of rats. METHODS:
      Fourteen Wistar rats weighing 285 +/- 12g were used. The study was done in a
      group whose open infected skin wounds were treated with topical application of
      simvastatin microemulsion (SIM, n=7) and a second group with wounds treated with
      saline 0.9 % (SAL, n=7). A bacteriological exam of the wounds fluid for gram
      positive and gram negative bacteria, the tecidual expression of TNFa and IL-1a by
      immunohistochemical technique, and histological analysis by HE stain were
      performed. RESULTS: The expression of TNFa could be clearly demonstrated in lower
      degree in skin wounds treated with simvastatin (668.6 +/- 74.7 im(2)) than in
      saline (2120.0 +/-327.1 im(2)). In comparison, wound tissue from SIM group
      displayed leukocyte infiltration significantly lower than that observed in SAL
      group (p<0.05). Culture results of the samples taken from wound fluid on fourth
      post treatment day revealed wound infection in only one rat of group simvastatin
      (SIM), where Proteus mirabilis, Escherichia coli and Enterobacter sp were
      isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial
      infection with more than 100,000 CFU/g was detected in all the wounds.
      CONCLUSION: In addition to its antiinflammatory properties, the protective
      effects of simvastatin in infected open skin wounds is able to reduce infection
      and probably has antibacterial action. The potential to treat these wounds with
      statins to ameliorate inflammation and infection is promising.

PMID- 17505658
TI  - Effects of the basic fibroblast growth factor and its anti-factor in the healing
      and collagen maturation of infected skin wound.
AB  - PURPOSE: The infection is one of the main factors that affect the physiological
      evolution of the surgical wounds. The aim of this work is to evaluate the effects
      of fibroblast growth factor (FGFa) and anti-FGFa in the healing, synthesis and
      maturation of collagen when topically used on infected skin wounds of rats.
      METHODS: An experimental study was performed in 60 male Wistar rats. All animals
      were divided in two groups (A and B). Each group was divided in three subgroups
      A1, B1; A2, B2 and A3, B3. After anesthesia with pentobarbital, two open squared
      wounds (1cm(2)), 4 cm distant to each other, were done in the dorsal skin of all
      the rats. In group A (n=30) the wounds were contaminated with multibacterial
      standard solution, and in group B(n=30) the wounds were maintained sterile. These
      wounds were named F1 (for inflammation analysis) and F2 (for collagen study). The
      open wounds of A1 and B1 rats were topically treated with saline solution, A2 and
      B2 were treated with FGFa and subgroups A3 and B3 were treated with FGFa and anti
      FGFa. The rats were observed until complete epitelization of F2 wounds for
      determination of healing time and the expression of types I and III collagen,
      using Picro Sirius Red staining. Inflammatory reaction in F1 wounds was studied
      using hematoxilineosin staining. The three variable was measured by the Image Pro
      Plus Media Cybernetics software. The statistical analysis was performed by ANOVA
      and Tukey test, considering p<0.05 as significant. RESULTS: It was observed that
      infection retarded significantly (p<0.05) the time of wound scarring and the
      topical application of FCFb reverted the inhibition of healing caused by
      bacteria. The inflammatory reaction was greater in the subgroup B2 than in B1 and
      A3, and the difference was significant (p<0.05). It was observed greater
      expression of type I collagen in all the subgroups treated with FCFb, when
      compared with the untreated subgroups. Type III collagen was significantly
      decreased in wounds of B3 rats, comparing to the other subgroups. CONCLUSIONS:
      The FCFb accelerated the healing of open infected wounds and contributed with
      maturation of collagen, enhancing the type I collagen density. The anti-FCFb
      antibody was able to attenuate the production of both type I and III collagen.

PMID- 17505659
TI  - Rapid restoration of colonic goblet cells induced by a hydrolyzed diet containing
      probiotics in experimental malnutrition.
AB  - PURPOSE: To investigate the effects of the addition of probiotic bacteria to a
      hydrolyzed diet on the recovery of goblet cells during renutrition in an animal
      model of malnutrition. METHODS: Twenty-six male Wistar rats (200-250g) were
      included in the study. Six were kept under normal conditions (sham group) while
      twenty received an aproteic diet for 15 days, and were randomized thereafter to
      receive a hydrolyzed diet containing (n=6; probiotic group) or not (n=6;
      hydrolyzed group) probiotics (10(6) cfu/g of Streptococcus thermophilus e
      Lactobacillus helveticus); or immediately killed (n=8; aproteic group).
      Histological slides containing cecal and sigmoid biopsies were used to counting
      the number of goblet cells and the goblet cells/colonocytes ratio. RESULTS:
      Malnutrition diminished the population of goblet cells in all sites. Goblet
      cells/colonocytes ratio of the probiotic group was significantly greater than
      hydrolyzed group at the ceccum (0.39 +/- 0.03 vs. 0.34 +/-0.02; p=0.02). Only
      rats fed with probiotics showed complete restoration of the normal goblet
      cells/colonocytes ratio at the sigmoid (0.37 +/- 0,02 vs. 0.22 +/- 0,03;
      p<0,001). CONCLUSION: Streptococcus thermophilus and Lactobacillus helveticus
      added to a renutrition diet enhance the recovery of mucosal atrophy induced by
      malnutrition and especially induce a rapid restoration of goblet cells population
      in the malnourished colonic mucosa.

PMID- 17505660
TI  - Sugarcane biopolymer patch in femoral artery angioplasty on dogs.
AB  - PURPOSE: The objective of this study was to evaluate the use of the sugarcane
      biopolymer membrane in femoral artery patch angioplasty on dogs. METHODS: Eight
      dogs were submitted to bilateral femoral artery patch angioplasty with a
      sugarcane biopolymer membrane patch on one side and e-PTFE patch on the
      contralateral side. This research was performed at Experimental Surgical Research
      Laboratory of the Centro de Ciencias da Saude at Universidade Federal de
      Pernambuco. The dogs were submitted to a new surgery at 180 days after the patch
      angioplasty in order to harvest the femoral artery. All the animals were
      evaluated by: clinical examination, measure of femoral artery diameter,
      arteriogram and Doppler fluxometry. Yet the material harvested was sent to
      histological study. Each animal served as its own control. RESULTS: In all
      vessels of both groups there were no cases of infection, aneurysm formation,
      rupture or pseudoaneurysm formation and thrombosis. In both groups it was
      observed a chronic inflammatory reaction with lymphocytes, neutrophils and
      fibrosis in the outer surface of the patches. It was observed fibrosis in the
      inner surfaces of all the patches. In e-PTFE patches occurred invasion by
      fibroblasts. CONCLUSION: The sugarcane biopolymer membrane can be used as a patch
      in femoral artery angioplasty on dogs.

PMID- 17505661
TI  - Cryoglobulinemia in chronic hepatitis C: clinical aspects and response to
      treatment with interferon alpha and ribavirin.
AB  - INTRODUCTION: The main extra-hepatic manifestation of hepatitis C is mixed
      cryoglobulinemia (MC). The aim of this study was to evaluate its prevalence among
      patients with chronic hepatitis C (CHC), to correlate its presence to host and
      virological variables and to the response to combined therapy with interferon
      alpha and ribavirin. CASUISTIC AND METHODS: 202 CHC naive patients (136 with
      chronic hepatitis and 66 with cirrhosis) were consecutively evaluated for the
      presence of cryoglobulins. Cryoprecipitates were characterized by
      immunoelectrophoresis and classified according to the Brouet's criteria. RESULTS:
      The prevalence of MC was 27% (54/202), and 24% of them (13/54) showed major
      clinical manifestation of the disease. Even though type III MC was more frequent
      (78%), symptomatic MC was more common in type II MC. The presence of cirrhosis
      (RR=2.073; IC95%=1.029-4.179; p=0.041), and age of the patients (RR=1.035;
      IC95%=1.008-1.062; p=0.01) were independently associated with the presence of
      cryoglobulins. No relationship was found with viral load and genotype. 102
      patients were treated with interferon alpha and ribavirin. Among these, 31 had
      MC. Sustained virological response (around 30%) was similar in patients with and
      without MC (p=0.971). CONCLUSION: MC represents a prevalent complication in
      patients with CHC, specially older and cirrhotic patients. Only 24% of these
      patients show clinical manifestation of the disease, specially those with type II
      MC. The presence of MC did not affect the response to therapy.

PMID- 17505662
TI  - Antiretroviral treatment for HIV infection/AIDS and the risk of developing
      hyperglycemia and hyperlipidemia.
AB  - A cross-sectional study with internal comparison groups was conducted to describe
      sociodemographic characteristics, as well as verify the association between the
      type of antiretroviral treatment used and hyperglycemia and hyperlipidemia, with
      special attention to the use of HIV protease inhibitors. The data was obtained
      through an interview questionnaire, as well as blood and urine samples that were
      collected for the laboratory exams. A total of 418 patients were interviewed. 46
      of these, however, met the exclusion criteria. The sample was therefore composed
      by 372 HIV positive patients, attended at the laboratory of the Correia Picanco
      State Hospital for the collection of blood, to estimate the HIV viral load and/or
      TCD4 cell counts from August to November 2000. The association between the
      variables was tested using the chi-square test and the p-value. A multiple
      logistic regression analysis was carried out to adjust for potential confounding
      factors. A greater frequency of patients with high glucose levels was observed
      among those making use of antiretroviral therapy without protease inhibitors, but
      the number of patients limited the comparisons. An association was verified
      between the total serum cholesterol level and the use of HIV protease inhibitors
      (p=0.047) even after controlling for age. An association was also observed
      between the triglyceride levels and the use of HIV protease inhibitors, which
      remained after adjustment for age, sex and creatinine levels (p<0.001). The
      levels of glucose and TSH, the presence of proteinuria and the practice of
      physical activity were not associated either with the levels of cholesterol or
      with the levels of tryglicerides thus they were not confounders of the
      associations described.

PMID- 17505663
TI  - High prevalence of malaria infection in Amazonas State, Venezuela.
AB  - This study was carried out to determine the incidence of malaria in an endemic
      region of Amazonas State, Venezuela. For this, 200 random samples were collected
      from symptomatic and asymptomatic individuals from San Fernando de Atabapo and
      Santa Barbara. Epidemiological factors were related to malaria infection, which
      was diagnosed by microscopy observation and amplification of the 18S rDNA
      sequence by PCR. Malaria prevalence in these populations was 28.5%, whilst P.
      vivax and P. falciparum prevalences were 12 and 17%, respectively. No infection
      by P. malariae was found. A mixed infection was found on an asymptomatic
      individual. Prevalence patterns differed between age groups depending on the
      Plasmodium species. We found that 34.8% of the P. vivax and 15.2% of the P.
      falciparum infections were asymptomatic. The use of nets was helpful to prevent
      P. vivax infection, but did not protect against P. falciparum infection. The
      results suggest the presence of more than one mosquito vector in the area,
      displaying a differential pattern of infection for each Plasmodium species. There
      appear to be risk factors associated with malaria infections in some individuals.
      The population based approach and PCR diagnosis improved the accuracy of the
      statistical analysis in the study.

PMID- 17505665
TI  - An immunofluorescence test for diagnosis of ophthalmic herpes in a mouse corneal
      model.
AB  - Herpes simplex virus type 1 (HSV-1) ophthalmic disease is the most common cause
      of corneal blindness in humans world-wide. Current culture techniques for HSV
      take several days and commercially available HSV laboratory based diagnostic
      techniques vary in sensitivity. Our study was conducted to evaluate the use of a
      quicker and simpler method to herpes ophthalmic diagnosis. Corneal smears were
      made by firm imprints of infected mouse eyes to glass slides, after smears were
      fixated with cold acetone, and an indirect immunofluorescence (IIF) method was
      performed using monoclonal antibodies in a murine model of ophthalmic herpes. Eye
      swabs from infected mice were inoculated in Vero cells for virus isolation.
      Cytology and histology of the eye were also performed, using hematoxylin-eosin
      routine. Mouse eyes were examined by slit-lamp biomicroscopy for evidence of
      herpetic disease at various times postinoculation. We made a comparative
      evaluation of sensitivity, specificity and speed of methods for laboratory
      detection of HSV. Our results indicate that this IIF method is quick, sensitive,
      specific and can be useful in the diagnosis of ophthalmic herpes as demonstrated
      in an animal model.

PMID- 17505666
TI  - The "in vitro" antifungal activity evaluation of propolis G12 ethanol extract on
      Cryptococcus neoformans.
AB  - Cryptococcosis is a worldwide disease caused by the etiological agent
      Cryptococcus neoformans. It affects mainly immunocompromised humans. It is
      relatively rare in animals only affecting those that have received prolonged
      antibiotic therapy. The propolis is a resin that can present several biological
      properties, including antibacterial, antifungal and antiviral activities. The
      standard strain C. neoformans ATTC 90112 was used to the antifungal evaluation.
      The tests were realized with propolis ethanol extract (PEE) G12 in concentrations
      from 0.1 to 1.6 mg mL-1. The evaluation of MIC and MFC were done according to
      DUARTE (2002)5. The inhibitory effect of PEE G12 on the fungal growing was seen
      at the concentration of 0.2 mg mL-1 and 1.6 mg mL-1 was considered a fungicidal
      one.

PMID- 17505668
TI  - In vitro and in situ activation of the complement system by the fungus Lacazia
      loboi.
AB  - Since there are no studies evaluating the participation of the complement system
      (CS) in Jorge Lobo's disease and its activity on the fungus Lacazia loboi, we
      carried out the present investigation. Fungal cells with a viability index of 48%
      were obtained from the footpads of BALB/c mice and incubated with a pool of
      inactivated serum from patients with the mycosis or with sterile saline for 30
      min at 37 masculineC. Next, the tubes were incubated for 2 h with a pool of
      noninactivated AB+ serum, inactivated serum, serum diluted in EGTA-MgCl2, and
      serum diluted in EDTA. The viability of L. loboi was evaluated and the fungal
      suspension was cytocentrifuged. The slides were submitted to immunofluorescence
      staining using human anti-C3 antibody. The results revealed that 98% of the fungi
      activated the CS by the alternative pathway and no significant difference in L.
      loboi viability was observed after CS activation. In parallel, frozen
      histological sections from 11 patients were analyzed regarding the presence of C3
      and IgG by immunofluorescence staining. C3 and IgG deposits were observed in the
      fungal wall of 100% and 91% of the lesions evaluated, respectively. The results
      suggest that the CS and immunoglobulins may contribute to the defense mechanisms
      of the host against L. loboi.

PMID- 17505670
TI  - Subcutaneous phaeohyphomycosis caused by Cladophialophora sp.: a case report.
AB  - A case of subcutaneous phaeohyphomycosis caused by Cladophialophora sp. is
      reported. The patient, an immunosuppressed host presented a nodule on the dorsum
      of the right hand which relapsed four months after excision. Dematiaceous septate
      hyphal and yeast like elements were seen in mycological and histological
      examination. The isolated fungus was identified on the basis of micro
      macromorphological and physiologic characteristics.

PMID- 17505669
TI  - Detection of parvovirus B19 infection in formalin-fixed and paraffin-embedded
      placenta and fetal tissues.
AB  - Parvovirus B19 infection was first discovered in 1975 and it is implicated in
      fetal death from hydrops fetalis the world over. Diagnosis is usually made
      through histological identification of the intranuclear inclusion in placenta and
      fetal organs. However, these cells may be scarce or uncharacteristic, making
      definitive diagnosis difficult. We analyzed histologically placentas and fetal
      organs from 34 cases of non-immune hydrops fetalis, stained with Hematoxylin and
      Eosin (HE) and submitted to immunohistochemistry and polymerase chain reaction
      (PCR). Of 34 tissue samples, two (5.9%) presented typical intranuclear inclusion
      in circulating normoblasts seen in Hematoxylin and Eosin stained sections,
      confirmed by immunohistochemistry and PCR. However, PCR of fetal organs was
      negative in one case in which the placenta PCR was positive. We concluded that
      parvovirus B19 infection frequency is similar to the literature and that
      immunohistochemistry was the best detection method. It is highly specific and
      sensitive, preserves the morphology and reveals a larger number of positive cells
      than does HE with the advantage of showing cytoplasmic and nuclear positivity,
      making it more reliable. Although PCR is more specific and sensitive in fresh or
      ideally fixed material it is not so in formalin-fixed paraffin-embedded tissues,
      frequently the only one available in such cases.

PMID- 17505671
TI  - Disseminated toxoplasmosis presenting as sepsis in two AIDS patients.
AB  - This report describes two patients who presented acute disseminated and severe
      toxoplasmosis as the first opportunistic disease related to acquired
      immunodeficiency syndrome. At admission, clinical and laboratory findings were
      similar to sepsis or septic shock and a fast evolutive course to death occurred
      in both cases. At necropsy, an inflammatory reaction and presence of a great
      number of Toxoplasma gondii cysts and tachyzoites were observed in most organs
      examined.

PMID- 17505672
TI  - Congenital toxoplasmosis in dizygotic twins, Parana, Brazil.
AB  - This is the first report of congenital toxoplasmosis in dizygotic twins in
      Brazil. We emphasize the need for early diagnosis of the mother and follow-up of
      children with suspected or confirmed infection from birth to adolescence, in
      order to avoid the hazard and damage from congenital toxoplasmosis.

PMID- 17505673
TI  - Natural infection of phlebotomines (Diptera: Psychodidae) in a visceral
      leishmaniasis focus in Mato Grosso do Sul, Brazil.
AB  - The main purpose of this study was to investigate natural infection by Leishmania
      in phlebotomine females in a visceral-leishmaniasis focus in Antonio Joao county
      in Mato Grosso do Sul State, Brazil. Between June and October 2003, the digestive
      tracts of 81 females captured in Aldeia Campestre, Aldeia Marangatu and Povoado
      Campestre were dissected. The females were separated by species, location, area
      and date of capture into 13 groups and kept in ethanol 70%. To identify the
      Leishmania species using the PCR technique, amplifications of the ribosomal-DNA
      (rDNA) and mini-exon genes were analyzed. Of the 81 specimens, 77 (95%) were
      Lutzomyia longipalpis, making this the most common species; only one specimen of
      each of the species Brumptomyia avellari, Evandromyia cortelezzii, Evandromyia
      lenti and Nyssomyia whitmani was found. Trypanosomatids were identified in eight
      of the nine groups of Lutzomyia longipalpis (10.39%) one group from Aldeia
      Campestre, one from Aldeia Marangatu and six from Povoado Campestre; of the eight
      groups, one from Aldeia Marangatu and another, with promastigotes forms also
      confirmed by dissection (1.23%) from Povoado Campestre, were identified by PCR as
      Leishmania chagasi (2.6%). The other groups gave negative results. These findings
      indicate that there is a high risk of leishmaniasis transmission in this area.

PMID- 17505674
TI  - Phenotypical and genotypical characterization of Bordetella pertussis strains
      isolated in Sao Paulo, Brazil, 1988-2002.
AB  - Whooping cough or pertussis was a major cause of childhood morbidity and
      mortality in the world until the introduction of a whole-cell vaccine in the
      1940's. However, since the early 1980's whooping cough cases have increased in
      many countries, becoming an important problem of public health. This increase may
      be due to accuracy of laboratory diagnosis and reporting of the disease, a
      decline in immunity over time, demographic changes, and adaptation of the
      bacterial population to vaccine-induced immunity. The purpose of this study was
      to analyze phenotypically and genotypically a collection of 67 Bordetella
      pertussis isolates recovered during the period 1988-2002 in Sao Paulo State,
      Brazil to determine their characteristics and relatedness. All isolates were
      submitted to susceptibility testing to erythromycin, serotyping, and 56 isolates
      were analyzed by Pulsed Field Gel Electrophoresis (PFGE). All isolates were
      susceptible to erythromycin and the majority of them belonged to serotype 1,3.
      The 56 isolates were classified into 11 PFGE profiles according to the
      differences in banding patterns. Although more than 60% of the isolates were
      recovered from patients aged less than three months, almost 15% of them were
      isolated from adolescents/adults evidencing the increase in the incidence of
      pertussis among this age group.

PMID- 17505675
TI  - Morphometric changes of Triatoma flavida Neiva, 1911 (Hemiptera:Triatominae) in
      the transition from sylvatic to laboratory conditions.
AB  - The one-generational metric changes occurring in Triatoma flavida (Hemiptera:
      Triatominae) when carried from its wild habitat (caves) to laboratory, were
      examined using traditional morphometric techniques. As for other species of
      Triatoma, Rhodnius or Panstrongylus studied in similar conditions, a significant
      reduction of head, thorax and wing size was observed. Sexual dimorphism of the
      wings, while present in the wild sample, was not detected anymore in the
      laboratory individuals. Biological significance and epidemiological importance
      are discussed.

PMID- 17505676
TI  - On the unknown ecological niche of Paracoccidioides brasiliensis: our hypothesis
      of 1989: present status and perspectives.
AB  - In 1989, CONTI DIAZ & RILLA published a hypothesis concerning the as yet unknown
      ecological niche of Paracoccidioides brasiliensis. The hypothesis proposed a
      highly efficient paracoccidioidal ecological strategy based on an important
      natural reservoir of the parasite, probably in heterothermic animals from fresh
      water environments. Further, the hypothesis proposed, a transient and variable
      residence in the soil with a wide aleuriospore dispersion throughout the
      environment together with an elevated capability of infecting humans, and
      domestic and wild animals. This paper analyzes scientific publications from the
      IX International Meeting on Paracoccidioidomycosis held in Aguas de Lindoia, Sao
      Paulo, Brazil from 2-5 October 2005, providing a comparative study among this
      articles and with other recently published papers and the hypothesis' postulates.
      Since various findings and observations appear to agree with the postulates, the
      pursuit of novel, specific research projects in the supposed reservoirs is
      recommended partially or fully to confirm the hypothesis using classical
      laboratorial methods and modern molecular biology techniques.

PMID- 17505677
TI  - Technological evaluations: the need for evidence-informed healthcare.

PMID- 17505678
TI  - Methylenetetrahydrofolate reductase gene polymorphism and its association with
      coronary artery disease.
AB  - CONTEXT AND OBJECTIVE: Obstructive coronary artery disease (CAD) is characterized
      by the deposition of atherosclerotic plaque on the coronary artery wall. Its
      manifestations depend on interactions between environmental and genetic risk
      factors. The aim of this work was to analyze the frequency of
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients with
      CAD and its association with plasma homocysteine levels. Risk factors for CAD
      were also evaluated. DESIGN AND SETTING: Retrospective with blind quantitative
      analysis, at Hospital de Base, Faculdade de Medicina de Sao Jose do Rio Preto.
      METHODS: One hundred and twenty-seven individuals were studied. All completed a
      questionnaire to analyze risk factors for CAD. MTHFR polymorphism was
      investigated by restriction fragment length analysis and correlated with the
      number of affected arteries and degree of arterial obstruction determined by
      coronary cineangiography, and with plasma homocysteine levels measured by liquid
      chromatography/sequential mass spectrometry. RESULTS: Smoking (p = 0.02) and high
      density lipoprotein cholesterol (p = 0.01) were associated with CAD. The C allele
      was the most prevalent in patients (0.61) and controls (0.66). There was no
      correlation between MTHFR/C677T polymorphism and plasma homocysteine levels.
      However, in patients with the TT genotype there was a correlation with the
      prevalence of coronary obstruction greater than 95% (p = 0.02) and the presence
      of two affected arteries (p = 0.04). CONCLUSIONS: The TT genotype is associated
      with coronary artery obstruction greater than 95% and the presence of two
      affected arteries. This confirms the relationship between genetic variants in
      specific patient subgroups and cardiovascular diseases.

PMID- 17505679
TI  - Thoracic sympathetic block reduces respiratory system compliance.
AB  - CONTEXT AND OBJECTIVE: Thoracic epidural anesthesia (TEA) following thoracic
      surgery presents known analgesic and respiratory benefits. However,
      intraoperative thoracic sympathetic block may trigger airway hyperreactivity.
      This study weighed up these beneficial and undesirable effects on intraoperative
      respiratory mechanics. DESIGN AND SETTING: Randomized, double-blind clinical
      study at a tertiary public hospital. METHODS: Nineteen patients scheduled for
      partial lung resection were distributed using a random number table into groups
      receiving active TEA (15 ml 0.5% bupivacaine, n = 9) or placebo (15 ml 0.9%
      saline, n = 10) solutions that also contained 1:200,000 epinephrine and 2 mg
      morphine. Under general anesthesia, flows and airway and esophageal pressures
      were recorded. Pressure-volume curves, lower inflection points (LIP), resistance
      and compliance at 10 ml/kg tidal volume were established for respiratory system,
      chest wall and lungs. Students t test was performed, including confidence
      intervals (CI). RESULTS: Bupivacaine rose 5 +/- 1 dermatomes upwards and 6 +/- 1
      downwards. LIP was higher in the bupivacaine group (6.2 +/- 2.3 versus 3.6 +/-
      0.6 cmH2O, p = 0.016, CI = -3.4 to -1.8). Respiratory system and lung compliance
      were higher in the placebo group (respectively 73.3 +/- 10.6 versus 51.9 +/-
      15.5, p = 0.003, CI = 19.1 to 23.7; 127.2 +/- 31.7 versus 70.2 +/- 23.1 ml/cmH2O,
      p < 0.001, CI = 61 to 53). Resistance and chest wall compliance showed no
      difference. CONCLUSION: TEA decreased respiratory system compliance by reducing
      its lung component. Resistance was unaffected. Under TEA, positive end-expiratory
      pressure and recruitment maneuvers are advisable.

PMID- 17505680
TI  - Vertical gastric plication versus Nissen fundoplication in the treatment of
      gastroesophageal reflux in children with cerebral palsy.
AB  - CONTEXT AND OBJECTIVE: Association between neurological lesions and
      gastroesophageal reflux disease (GERD) in children is very common. When surgical
      treatment is indicated, the consensus favors the fundoplication technique
      recommended by Nissen, despite its high morbidity and relapse rates. Vertical
      gastric plication is a procedure that may have advantages over Nissen
      fundoplication, since it is less aggressive and more adequately meets anatomical
      principles. The authors proposed to compare the results from the Nissen and
      vertical gastric plication techniques. DESIGN AND SETTING: Randomized prospective
      study within the Postgraduate Surgery and Experimentation Program of UNIFESP-EPM,
      at Hospital do Servidor Publico Estadual (IAMSPE) and Hospital Municipal Infantil
      Menino Jesus. METHODS: Fourteen consecutive children with cerebral palsy attended
      between November 2003 and July 2004 were randomized into two groups for surgical
      treatment of GERD: NF, Nissen fundoplication (n = 7); and VGP, vertical gastric
      plication (n = 7). These were clinically assessed by scoring for signs and
      symptoms, evaluation of esophageal pH measurements, duration of the operation,
      intra and postoperative complications, mortality and length of hospital stay.
      RESULTS: The mean follow-up was 5.2 months; symptoms were reduced by 42.8% (NF)
      (p = 0.001) and 57.1% (VGP) (p = 0.006). The Boix-Ochoa score was favorable for
      both groups: NF (p < 0.001) and VGP (p < 0.042). The overall mortality was 14.28%
      in both groups and was due to causes unrelated to the surgical treatment.
      CONCLUSION: The two operative procedures were shown to be efficient and
      efficacious for the treatment of GERD in neuropathic patients, over the study
      period.

PMID- 17505681
TI  - The effects of an individualized exercise intervention on body composition in
      breast cancer patients undergoing treatment.
AB  - CONTEXT AND OBJECTIVE: Changes in metabolism have been reported in the majority
      of patients undergoing cancer treatment, and these are usually characterized by
      progressive change in body composition. The effects of aerobic exercise programs
      to combat the cancer and cancer treatment-related side effects, which include the
      negative changes in body composition, have been extensively reported in the
      literature. However, few resistance exercise intervention studies have
      hypothesized that breast cancer patients might benefit from this type of
      exercise. The purpose of this study was to determine whether exercise protocols
      that emphasize resistance training would change body composition and strength in
      breast cancer patients undergoing treatment. DESIGN AND SETTING: Randomized
      controlled trial, at the Campus Recreation Center and Rocky Mountain Cancer
      Rehabilitation Institute of the University of Northern Colorado, and the North
      Colorado Medical Center. METHODS: Twenty inactive breast cancer patients were
      randomly assigned to a 21-week exercise group (n = 10) or a control group (n =
      10). The exercise group trained at low to moderate intensity for 60 minutes on
      two days/week. The primary outcome measurements included body composition
      (skinfold method) and muscle strength (one repetition maximum). RESULTS:
      Significant differences in lean body mass, body fat and strength (p = 0.004, p =
      0.004, p = 0.025, respectively) were observed between the groups at the end of
      the study. CONCLUSION: The results suggest that exercise emphasizing resistance
      training promotes positive changes in body composition and strength in breast
      cancer patients undergoing treatment.

PMID- 17505682
TI  - Multidimensional pain assessment of preterm newborns at the 1st, 3rd and 7th days
      of life.
AB  - CONTEXT AND OBJECTIVE: It is challenge to assess and treat pain in premature
      infants. The objective of this study was to compare the multidimensional pain
      assessment of preterm neonates subjected to an acute pain stimulus at 24 hours,
      72 hours and seven days of life. DESIGN AND SETTING: Prospective cohort study, at
      Universidade Federal de Sao Paulo. METHODS: Eleven neonates with gestational age
      less than 37 weeks that needed venepuncture for blood collection were studied.
      The exclusion criteria were Apgar score < 7 at five minutes, presence of any
      central nervous system abnormality, and discharge or death before seven days of
      life. Venepuncture was performed in the dorsum of the hand, and the heart rate,
      oxygen saturation and pain scales [Neonatal Facial Coding System (NFCS), Neonatal
      Infant Pain Scale (NIPS), and Premature Infant Pain Profile (PIPP)] were assessed
      at 24 hours, 72 hours and 7 days of life. NFCS and NIPS were evaluated prior to
      procedure (Tpre), during venepuncture (T0), and two (T2) and five (T5) minutes
      after needle withdrawal. Heart rate, O2 saturation and PIPP were measured at Tpre
      and T0. Mean values were compared by repeated-measurement analysis of variance.
      RESULTS: The pain parameters did not differ at 24 hours, 72 hours and 7 days of
      life: heart rate (p = 0.22), oxygen saturation (p = 0.69), NFCS (p = 0.40), NIPS
      (p = 0.32) and PIPP (p = 0.56). CONCLUSION: Homogeneous pain scores were observed
      following venepuncture in premature infants during their first week of life.

PMID- 17505683
TI  - Efficacy of National Nosocomial Infection Surveillance score, acute-phase
      proteins, and interleukin-6 for predicting postoperative infections following
      major gastrointestinal surgery.
AB  - CONTEXT AND OBJECTIVE: Postoperative infections should be detected earlier. We
      investigated the efficacy of the National Nosocomial Infection Surveillance
      (NNIS) score, interleukin-6 (IL-6) and various acute-phase proteins for
      predicting postoperative infections. DESIGN AND SETTING: Case series study at the
      Julio Muller University Hospital. METHODS: Thirty-two patients who underwent
      major gastrointestinal procedures between June 2004 and February 2005 were
      studied. The NNIS score and the evolution of serum IL-6 and various acute-phase
      proteins (C-reactive protein [CRP], albumin, prealbumin and transferrin) were
      correlated with postoperative infections and length of hospital stay (LOS).
      RESULTS: NNIS > 1 (p = 0.01) and low preoperative albumin (p = 0.02)
      significantly correlated with infection. IL-6 and CRP increased significantly
      more in patients with infections. Multivariate analysis showed greater risk of
      infection when NNIS > 1 (odds ratio, OR = 10.66; 95% confidence interval, CI: 1.1
      102.0; p = 0.04); preoperative albumin < 3 g/dl (OR = 8.77; 95% CI: 1.13-67.86; p
      = 0.03); CRP > 30 mg/l on the second postoperative day (OR = 8.27; 95% CI: 1.05
      64.79; p = 0.03) and > 12 mg/l on the fifth postoperative day (OR = 25.92; 95%
      CI: 2.17-332.71; p < 0.01); and IL-6 > 25 pg/ml on the fifth postoperative day
      (OR = 15.46; 95% CI: 1.19-230.30; p = 0.03). Longer LOS was associated with
      cancer, transferrin, IL-6 and albumin (p < 0.05). CONCLUSIONS: NNIS, albumin, CRP
      and IL-6 may be useful as predictive markers for postoperative infections. For
      predicting LOS, malignant condition, transferrin, albumin and IL-6 are useful.

PMID- 17505684
TI  - The impact of a community intervention to improve cervical cancer screening
      uptake in the Amazon region of Brazil.
AB  - CONTEXT AND OBJECTIVE: In the northern region of Brazil, cervical cancer is the
      most important cause of cancer-related deaths among women. There is considerable
      likelihood, however, that official incidence and mortality figures are greatly
      underestimated. The aim of this study was to estimate the repercussions from
      improvement in cervical cancer screening programs on the incidence of pre
      invasive and invasive cervical lesions in a municipality in this region. DESIGN
      AND SETTING: This was a quasi-experimental study that assessed process dimensions
      relevant to the program objectives. The study comprised a sample of 2,226 women
      seen at primary healthcare units in Cruzeiro do Sul, a small city in the
      Brazilian Amazon region, from April 2003 to July 2004. METHODS: Women were
      recruited through local radio advertisements and by oral communication from the
      investigators. The women answered a structured questionnaire and underwent pelvic
      examination, which included Papanicolaou (Pap) smears and naked-eye inspection of
      the cervix after applying diluted acetic acid. Women with positive Pap smears or
      abnormal gynecological examination were referred for colposcopy and possible
      biopsy, diathermic large loop excision of the transformation zone or conization.
      RESULTS: The results obtained were compared with historical official data
      retrieved from the Brazilian Ministry of Health's database. Intervention resulted
      in a 40% increase in positive Pap smears and detection of cancer was nine times
      higher than had been observed in routine screening. CONCLUSIONS: Detection of pre
      invasive and invasive cervical lesions in the intervention group was remarkably
      higher than among women seen during routine screening.

PMID- 17505685
TI  - Predictors of quality-of-life improvement following pulmonary resection due to
      lung cancer.
AB  - CONTEXT AND OBJECTIVE: There is increasing involvement of health professionals in
      organizing protocols to determine the impact of lung surgery on functional state
      and activities of daily living, with the aim of improving quality of life (QoL).
      The objective of this study was to investigate predictors of QoL improvement
      among patients undergoing parenchyma resection due to lung cancer. DESIGN AND
      SETTING: Prospective study, at teaching hospital of Universidade Estadual de
      Campinas (Unicamp). METHODS: 36 patients with lung cancer diagnosis were assessed
      before surgery and on the 30th, 90th and 180th days after surgery. The Short-Form
      Health Survey (SF-36) was used as the dependent variable. The independent
      variables were the Hospital Anxiety and Depression (HAD) scale, a six-minute
      walking test (6-MWT), a visual analogue scale for pain, forced vital capacity
      (FVC), type of surgery and use of radiotherapy and chemotherapy. Generalized
      estimation equations (GEE) were utilized. RESULTS: The median age for these 20
      men and 16 women was 55.5 +/- 13.4 years. Both FVC and 6-MWT were predictors of
      improvement in the physical dimensions of QoL (p = 0.011 and 0.0003,
      respectively), as was smaller extent of surgical resection (p = 0.04). The social
      component of QoL had improved by the third postoperative month (p = 0.0005).
      CONCLUSION: The predictors that affected QoL positively were better FVC and 6-MWT
      results and less extensive lung resection. Three months after the surgery, an
      improvement in social life was already seen.

PMID- 17505686
TI  - Hepatorenal syndrome: an update.
AB  - Hepatorenal syndrome (HRS) is the development of renal failure in patients with
      chronic previous liver disease, without clinical or laboratory evidence of
      previous kidney disease. It affects up to 18% of cirrhotic patients with ascites
      during the first year of follow-up, reaching 39% in five years and presenting a
      survival of about two weeks after its establishment. HRS diagnosis is based on
      clinical and laboratory data. The occurrence of this syndrome is related to the
      mechanism for ascites development, involving vasoconstriction, low renal
      perfusion, water and sodium retention, increased plasma volume, and consequent
      overflow at the splanchnic level. Renal vasoactive mediators like endothelin 1,
      thromboxane A2, and leukotrienes are also involved in the genesis of this
      syndrome, which culminates in functional renal insufficiency. The treatment of
      choice can be pharmacological or surgical, although liver transplantation is the
      only permanent and effective treatment, with a four-year survival rate of up to
      60%. Liver function recovery is usually followed by renal failure reversion.
      Early diagnosis and timely therapeutics can increase life expectancy for these
      patients while they are waiting for liver transplantation as a definitive
      treatment.

PMID- 17505687
TI  - Dipyrone and acetaminophen: correct dosing by parents?
AB  - CONTEXT AND OBJECTIVE: Several studies in developed countries have documented
      that a significant percentage of children are given inappropriate doses of
      acetaminophen and ibuprofen. The objective of this paper was to investigate
      parents' accuracy in giving dipyrone and acetaminophen to their children, in a
      poor region. DESIGN AND SETTING: Cross-sectional study at the pediatric emergency
      department of Instituto Materno-Infantil Prof. Fernando Figueira, a teaching
      hospital in Pernambuco. METHODS: The inclusion criteria were age between 3 and 36
      months, main complaint of fever and at least one dose of dipyrone or
      acetaminophen given to the child during the 24 hours preceding their arrival at
      the emergency department. The mothers were asked for demographic information and
      about the antipyretic doses given, which were compared with the recommended
      dosage. RESULTS: Among the 200 patients studied, 117 received dipyrone and 83
      received acetaminophen. Overall, 75 % received an incorrect dose of antipyretic.
      Of the patients who received dipyrone, 105 (89.7%) were given an incorrect dose;
      16 (15.2%) received too little dipyrone, and 89 (84.8%) received too much. Of the
      patients who received acetaminophen, 45 (54.2%) were given an incorrect dose; 38
      (84.4%) received too little acetaminophen, and 7 (15.6%) received too much. There
      were no differences in maternal and child characteristics between the groups
      receiving correct and incorrect doses of medication, except for the type of
      medication (dipyrone versus acetaminophen). CONCLUSIONS: Most of the children
      treated were given inappropriate doses, mainly dipyrone overdosing and
      acetaminophen underdosing.

PMID- 17505688
TI  - Methylene blue for clinical anaphylaxis treatment: a case report.
AB  - CONTEXT AND OBJECTIVE: Nitric oxide has a pathophysiological role in modulating
      systemic changes associated with anaphylaxis. Nitric oxide synthase inhibitors
      may exacerbate bronchospasm in anaphylaxis and worsen clinical conditions, with
      limited roles in anaphylactic shock treatment. The aim here was to report an
      anaphylaxis case (not anaphylactic shock), reversed by methylene blue (MB), a
      guanylyl cyclase inhibitor. CASE REPORT: A 23-year-old female suddenly presented
      urticaria and pruritus, initially on her face and arms, then over her whole body.
      Oral antihistamine was administered initially, but without improvement in
      symptoms and signs until intravenous methylprednisolone 500 mg. Recurrence
      occurred after two hours, plus vomiting. Associated upper respiratory distress,
      pulmonary sibilance, laryngeal stridor and facial angioedema (including erythema
      and lip edema) marked the evolution. At sites with severe pruritus, petechial
      lesions were observed. The clinical situation worsened, with dyspnea, tachypnea,
      peroral cyanosis, laryngeal edema with severe expiratory dyspnea and deepening
      unconsciousness. Conventional treatment was ineffective. Intubation and
      ventilatory support were then considered, because of severe hypoventilation. But,
      before doing that, based on our previous experience, 1.5 mg/kg (120 mg) bolus of
      4% MB was infused, followed by one hour of continuous infusion of another 120 mg
      diluted in dextrose 5% in water. Following the initial intravenous MB dose, the
      clinical situation reversed completely in less than 20 minutes, thereby avoiding
      tracheal intubation. CONCLUSION: Although the nitric oxide hypothesis for MB
      effectiveness discussed here remains unproven, our intention was to share our
      accumulated cohort experience, which strongly suggests MB is a lifesaving
      treatment for anaphylactic shock and/or anaphylaxis and other vasoplegic
      conditions.

PMID- 17505689
TI  - Left ventricular hypertrabeculation/noncompaction: a cardiac manifestation of
      myopathy?

PMID- 17505690
TI  - Assessment of HFE mutations in patients with iron overload.

PMID- 17505692
TI  - Prospective study of the treatment of infected hip arthroplasties with or without
      the use of an antibiotic-loaded cement spacer.
AB  - PURPOSE: Our purpose was to compare 2 methods of treatment of chronic infection
      in hip arthroplasties--with or without an antibiotic-loaded cement spacer.
      METHODS: In a prospective study, we treated 68 infected hip arthroplasties with
      discharging sinuses and bone loss, comparing 30 patients treated in 2 stages
      without the use of a spacer (control group) and 38 patients treated with a
      vancomycin-loaded spacer (study group). The average follow-up was 4 years (2-8.5
      years). One patient died of unrelated causes 4 months after first-stage surgery
      and was excluded from the study. RESULTS: The 2-stage surgery without spacer
      controlled the infection in 66.7% of patients, and the 2-stage surgery using the
      spacer controlled it in 89.1% (P < 0.05). At last follow-up, the average Harris
      Hip Score increased from 19.3 to 69.0 in the control group versus 19.7 to 75.2 in
      the study group (P > 0.05). The average leg length discrepancy was 2.6 cm in the
      control group and 1.5 cm in the study group (P < 0.05). The patients treated with
      a spacer had better clinical results (81.5% of patients with good results against
      60.0% for the control group). CONCLUSION: The use of an antibiotic-loaded spacer
      in the 2-stage treatment of infected hip arthroplasties provides better infection
      control with good functional results and is superior to treatment in 2 stages
      without a spacer. LEVEL OF EVIDENCE: Therapeutic study, Level I-1.

PMID- 17505693
TI  - Percutaneous prostate cryoablation as treatment for high-risk prostate cancer.
AB  - PURPOSE: To evaluate percutaneous cryotherapy as a primary treatment option for
      high-risk prostate cancer patients. PATIENTS AND METHODS: From October 2000 to
      February 2005, 21 high-risk (Gleason e.8 and/or PSA > 10 and/or stage > T2a)
      prostate cancer patients underwent 24 percutaneous prostate cryoablation
      procedures. Patients' median age was 70.9, and the average pretreatment PSA was
      19.5 ng/dL. The follow-up period ranged from 6 to 60 months (median, 41 months).
      RESULTS: The PSA failure rate was 39%, 52.9%, and 42.8% at 12, 24, and 60 months
      of follow-up, respectively. Overall complication rates were low, with 8% of
      urinary incontinence and no cases of rectal injury; however, 96% of erectile
      dysfunction occurred. The cryoablation procedure failed in 12 patients (57.2%); 7
      (58.3%) of these were local failures (positive prostate biopsies). CONCLUSION:
      Percutaneous cryoablation of the prostate is a safe minimally invasive treatment,
      but it has poor PSA-free survival outcomes in high-risk prostate cancer patients.

PMID- 17505694
TI  - The impact of noninvasive ventilation during the physical training in patients
      with moderate-to-severe chronic obstructive pulmonary disease (COPD).
AB  - OBJECTIVE: To evaluate the influence of physical training with or without
      noninvasive ventilation at 2 levels of pressure in the airways (BiPAP) in
      patients with chronic obstructive pulmonary disease. METHODS: Eighteen patients
      with FEV(1) = 34 +/- 8% of predicted values, mean age of 68 +/- 9 years were
      randomly distributed into 2 groups, one group performing physical training on a
      treadmill and the other group performing physical training associated with BiPAP
      (physical training+B), for 30 minutes, 3 times a week for 12 weeks. The training
      velocity was based on a test of cardiopulmonary force performed pre- and
      postintervention, which registered the values for heart rate, systolic blood
      pressure, diastolic blood pressure, peripheral oxygen saturation, blood lactate,
      sensation of dyspnea, respiratory muscle strength, and analysis of gases expired
      such as oxygen consumption and the production of carbon dioxide. RESULTS: For
      both groups, there was a significant improvement in dyspnea and peripheral oxygen
      saturation at identical levels of physical exercise, in distance walked during
      the physical training, and in respiratory muscle strength (P < 0.05). Only the
      physical training+B group had a significant improvement in heart rate, systolic
      blood pressure, and oxygen consumption after training (P < 0.05). Significant
      reductions of blood lactate were observed at identical levels of exercise in
      physical training+B when compared to isolated physical training (from 1.3 +/- 0.7
      mMol/L versus 2.5 +/- 0.9 mMol/L, (P < 0.05), respectively). CONCLUSION: Physical
      training associated with BiPAP enhanced the oxidative muscular capacity and could
      be an adjunctive recourse for physical rehabilitation in patients with chronic
      obstructive pulmonary disease.

PMID- 17505695
TI  - Metabolic test with fluorine-18-fluorodeoxyglucose in staging and detection of
      residual tumor or recurrence in Hodgkin lymphoma.
AB  - OBJECTIVE: The metabolic test using 18F-fluorodeoxyglucose is a useful tool for
      the management of patients with Hodgkin lymphoma, either for staging purposes or
      for the evaluation of suspicious masses that can frequently occur after
      treatment. The aim of the present study was to investigate the value of the 18F
      fluorodeoxyglucose test performed with a dual-head coincident gamma camera (CGC
      PET with fluorodeoxyglucose) for the staging and the detection of residual tumor
      of patients with Hodgkin lymphoma. METHODS: Thirty-eight consecutive patients
      were included in this retrospective study; the metabolic test comprising CGC-PET
      with FDG was done in 18 patients for staging work-up (Group 1), and the results
      were compared to conventional clinical staging procedures that included computed
      tomography scans and bone marrow biopsy. The remaining 20 patients were evaluated
      with CGC-PET with fluorodeoxyglucose due to the presence of residual masses or a
      new lesion (Group 2). RESULTS: The 18F-Fluorodeoxyglucose metabolic test, CGC-PET
      with fluorodeoxyglucose, upstaged 5 (27%) of the Group 1 patients and detected
      more lesions (45) than conventional methods of staging (33). Of the 20 patients
      in Group 2, 11 had positive18F-fluorodeoxyglucosetests, and a viable tumor was
      confirmed in 9 patients. Regarding the 9 patients with negative
      fluorodeoxyglucose metabolic tests, the 1-year probability of recurrence was
      11.8%. The sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of the CGC-PET with fluorodeoxyglucose test were
      90%, 80%, 82%, 89%, and 85% respectively. CONCLUSIONS: The metabolic test
      comprising CGC-PET with fluorodeoxyglucose had a higher diagnostic accuracy than
      conventional methods in the staging of Hodgkin lymphoma and thus is a valuable
      noninvasive tool for the diagnosis of suspicious lesions.

PMID- 17505696
TI  - Isokinetic torque peak and hamstrings/quadriceps ratios in endurance athletes
      with anterior cruciate ligament laxity.
AB  - PURPOSE: To evaluate torque and the hamstring/quadriceps ratio of the knee of
      athletes with and without anterior cruciate ligament laxity. METHODS: Twenty
      eight male athletes, 19 without anterior cruciate ligament laxity and 9 with
      anterior cruciate ligament laxity, were evaluated with an isokinetic machine
      model Cybex 770. The peak torque of quadriceps and hamstrings was compared, and
      the hamstring/quadriceps ratio on the constant angular speed of 60 masculine per
      second were also compared. RESULTS: In athletes with anterior cruciate ligament
      laxity, the peak torque values (right and left knees) of flexors (120 +/- 15 and
      116 +/- 15 Nm) and of extensors (218 +/- 36 Nm and 207 +/- 26 Nm) were not
      different than those of athletes without laxity (109 +/- 21 Nm and 111 +/- 22 Nm;
      191 +/- 5 Nm and 188 +/- 35 Nm). The hamstring/quadriceps ratio of athletes with
      laxity (right: 57 +/- 6% and left: 56 +/- 8%) did not differ from those without
      anterior cruciate ligament laxity (right: 58 +/- 9% and left: 58 +/- 7%).
      CONCLUSIONS: The anterior cruciate ligament laxity of long distances running
      athletes did not significantly alter the peak torque of flexors and of extensors
      or the hamstring/quadriceps ratio.

PMID- 17505697
TI  - A prospective study of dentoalveolar trauma at the Hospital das Clinicas, Sao
      Paulo University Medical School.
AB  - PURPOSE: This prospective study evaluated the profile of patients with
      dentoalveolar trauma assisted at the emergency room of the Oral and Maxillofacial
      Trauma and Surgery Service at the Hospital das Clinicas, Sao Paulo University
      Medical School (Brazil). METHODS: A prospective study by a questionnaire applied
      during the first attendance of those patients, in a period of eight months.
      RESULTS: The collected data were statistically analyzed. It was observed that
      4.7% of the patients that sought treatment at the Service had sustained
      dentoalveolar trauma and among these 74% were male. The most affected individuals
      were children aged 0 to 5 years and fall was the most prevalent etiologic factor.
      Avulsion and coronal/crown-root fractures were the most common types of
      dentoalveolar traumatic injures. As the age increases, the most common etiologic
      factors are traffic accidents and physical assault. CONCLUSION: The incidence of
      dentoalveolar trauma decreased with age and the main etiologic factors in adult
      patients were traffic accidents and physical assault.

PMID- 17505698
TI  - Brazilian-Portuguese version and applicability questionnaire of the mobility
      index for ankylosing spondyliti.
AB  - PURPOSE: To translate and adapt the Bath Ankylosing Spondylitis Methodology Index
      (BASMI) - a metrological measurement for the assessment of patients with
      ankylosing spondylitis to Brazilian-Portuguese and to analyze the applicability
      of the questionnaire. METHODS: The Brazilian-Portuguese version of the Bath
      Ankylosing Spondylitis Methodology Index was achieved through a translation and
      back-translation process. This new Bath Ankylosing Spondylitis Methodology Index
      version was administered to 25 consecutive patients with ankylosing spondylitis
      who met the 1984 New York criteria for ankylosing spondylitis and were followed
      in the Soronegative Spondyloarthropathy Unit of the Rheumatology Division, Sao
      Paulo University Medical School, from May to November 2005. In order to evaluate
      the applicability of the questionnaire, it was administered to patients by 2
      separate observers, A and B (Rheumatologists), enabling inter-observer test
      analysis. After 2 weeks, the second interview was administered to the same
      patients by observer A only to analyze the intra-observer test. All interviews
      were conducted in the morning. The Pearson coefficient correlation was used to
      evaluate applicability. RESULTS: There was no conflict stemming from translation
      and re-translation of Bath Ankylosing Spondylitis Methodology Index
      questionnaire, and cross-cultural adaptation proved unnecessary. All components
      had statistically significant coefficients for intra- and inter-observational
      applicability, with scores ranging from 0.85 to 1.00 and 0.80 to 0.94,
      respectively. DISCUSSION: The Brazilian-Portuguese version of the Bath Ankylosing
      Spondylitis Methodology Index proved to be an applicable instrument for analyzing
      the mobility index of Brazilian patients with ankylosing spondylitis.

PMID- 17505699
TI  - Effect of hemodialysis on intra-abdominal pressure.
AB  - OBJECTIVE: To study the effect of hemodialysis on intra-abdominal pressure.
      METHODS: Five patients admitted between July and November of 2003 were evaluated
      in the intensive care unit. Intra-abdominal pressure was measured before and
      after hemodialysis, maintaining the ventilatory parameters except for PEEP
      (positive-end expiratory pressure). RESULTS: Intra-abdominal pressure was
      significantly reduced by hemodialysis in all the 5 patients. CONCLUSION:
      Hemodialysis significantly reduced intra-abdominal pressure in the 5 patients, an
      effect which could have influence over other organic systems. This reduction is
      related to the weight variation before and after hemodialysis, as well as to the
      loss of volume caused by this procedure.

PMID- 17505700
TI  - Effect of a low-dose oral contraceptive on venous endothelial function in healthy
      young women: preliminary results.
AB  - BACKGROUND: A possible increase in the incidence of venous thromboembolic events
      has been reported among users of third generation oral contraceptives. The
      objective of this study was to evaluate the effect of a low dose oral
      contraceptive (15 microg ethinyl estradiol/60 microg gestodene) on the venous
      endothelial function of healthy young women. METHODS: Prospective case control
      study using the dorsal hand vein technique. Venous endothelial function was
      evaluated at baseline and after 4 months in the oral contraceptive users group
      (11 women) and in a control group (9 women). After preconstriction of the vein
      with phenylephrine, dose-response curves for acetylcholine and sodium
      nitroprusside were constructed. RESULTS: In the contraceptive users group, a
      reduction occurred in the maximum venodilation response to acetylcholine and
      sodium nitroprusside after 4 months of oral contraceptive use, but this
      difference was not statistically significant (P > 0.05). No significant changes
      were detected in maximum venodilation responses to acetylcholine and sodium
      nitroprusside at the 4-month time point in the control group. CONCLUSION: This
      study found no significant impairment of endothelium-dependent or independent
      venodilation in healthy young women following oral contraceptive use. Further
      studies are necessary using the same methodology in a larger sample over a longer
      follow-up period.

PMID- 17505701
TI  - Williams Syndrome: development of a new scoring system for clinical diagnosis.
AB  - OBJECTIVE: To develop a scoring system based on clinical findings to assist
      pediatricians in the diagnosis of William syndrome and to delineate when the
      fluorescent in-situ hybridization test to detect the microdeletion at 7q11.23 may
      be needed. METHODS: The fluorescent in-situ hybridization test was performed on
      20 patients presenting William syndrome suggestive clinical features. Eleven
      studies were selected from the literature in which there were 2 groups: patients
      with positive or negative fluorescent in-situ hybridization tests. Forty-two
      clinical characteristics were compared to those reported in the literature to
      determine which ones were associated with the affected patients (ie, bearing
      deletions) using meta-analysis. The 2-tailed Fisher exact test were used so that
      the frequency of findings observed in fluorescent in-situ hybridization positive
      and fluorescent in-situ hybridization negative patients could be compared in the
      present study together with the patients from the literature. We developed a
      scoring system based on clinical findings and their significant associations with
      patients with positive fluorescent in-situ hybridization tests. From the mean and
      standard-deviation values of the data from our patients, we determined the cut
      off score that that indicated the need for a fluorescent in-situ hybridization
      test to confirm diagnosis. RESULTS: Seventeen patients were fluorescent in-situ
      hybridization positive, and 3 were fluorescent in-situ hybridization negative.
      The more discriminative findings among fluorescent in-situ hybridization positive
      patients were the following: typical facies, low birth weight, feeding
      difficulties, constipation, supravalvar aortic stenosis, mental retardation, and
      friendly personality. The distribution of the points among the 20 patients ranged
      from 19 to 28 points with a mean value of 23.3 out of a possible total of 31
      points. The cut-off score that indicated the need for a fluorescent in-situ
      hybridization test was 20. CONCLUSIONS: Our scoring system enables physicians to
      differentiate between those individuals who can be reliably diagnosed as having
      Williams syndrome solely from the clinical findings and those who need to undergo
      fluorescent in-situ hybridization testing for a correct diagnosis.

PMID- 17505702
TI  - Classical osteoblastoma, atypical osteoblastoma, and osteosarcoma: a comparative
      study based on clinical, histological, and biological parameters.
AB  - OBJECTIVE: To investigate the biological behavior of classical and atypical
      osteoblastomas in comparison to osteosarcomas. METHODS: Based on histological
      parameters, 30 osteoblastomas were subclassified as classical osteoblastomas
      (23/30) or atypical osteoblastoma (high cellularity, prominent blue osteoid, and
      epithelioid osteoblasts--7/30). Comparative immunohistochemical and clinical
      analysis was performed in 17 cases of patients with high-grade osteosarcoma.
      Formalin-fixed, paraffin-embedded archival tissue was immunostained for p53 and
      proliferation cell nuclear antigen. Tumors with positive p53 stain underwent
      molecular analyses for fragments of exon 10. RESULTS: The mean proliferating cell
      nuclear antigen indexes for classical osteoblastoma, atypical osteoblastoma, and
      osteosarcoma were 33%, 61%, and 79%, respectively. The atypical subgroup showed
      similar results to those of the osteosarcoma group (P < 0.001). p53 protein was
      detected in 4 (13%) osteoblastomas (3 of these were atypical osteoblastoma), and
      4 osteosarcomas (23%) also showed p53 positivity. DNA mutation performed in p53
      positive cases was confirmed in exon 10 in 2 atypical osteoblastomas (2/3), 1
      classical osteoblastoma (1/1), and 1 osteosarcoma (1/4). Disease recurrence was
      correlated with p53 expression (P = 0.009), atypical subtype (P = 0.031),
      spiculated blue bone on histology (P = 0.018), and proliferating-cell nuclear
      antigen labeling index > or =40 (P = 0.015). CONCLUSION: These results validate
      atypical osteoblastoma as an entity, with p53 and proliferation cell nuclear
      antigen immuno-expression closer to that of osteosarcoma than of classical
      osteoblastoma. Proliferating cell nuclear antigen labeling index and p53 may be
      useful predictors of recurrence.

PMID- 17505703
TI  - Chemonucleolysis in lumbar disc herniation: a meta-analysis.
AB  - PURPOSE: To carry out a systematic review and meta-analysis of the efficacy of
      chemonucleolysis in the treatment of lumbar disc herniation. METHODS: Clinical
      trials were selected from 3 electronic databases (The Cochrane Controlled Trials
      Register, MEDLINE, and EMBASE). Data were analyzed with the software STATA, using
      the meta command. RESULTS: Twenty-two clinical trials were eligible. For
      chemonucleolysis versus placebo, the summary risk ratio estimate for pain relief
      as outcome was 1.51 (95% CI: 1.27-1.80). The summary estimate was 1.07 (95% CI:
      0.95-1.20) for the comparison between chymopapain and collagenase. Regarding
      chemonucleolysis with chymopapain versus surgery, the fixed-effect summary
      estimate of effect for pain relief was 0.93 (95% CI: 0.88-0.98) with surgery as
      the reference group. In this case, heterogeneity was statistically significant.
      CONCLUSIONS: Chemonucleolysis with chymopapain was superior to placebo and was as
      effective as collagenase in the treatment of lumbar disc prolapse. Results for
      studies comparing chemonucleolysis with surgery were heterogeneous, making it
      difficult to interpret the summary measure of effect.

PMID- 17505704
TI  - The importance of surfactant on the development of neonatal pulmonary diseases.
AB  - Pulmonary surfactant is a substance composed of a lipoprotein complex that is
      essential to pulmonary function. Pulmonary surfactant proteins play an important
      role in the structure, function, and metabolism of surfactant; 4 specific
      surfactant proteins have been identified: surfactant proteins-A, surfactant
      proteins-B, surfactant proteins-C, and surfactant proteins-D. Clinical,
      epidemiological, and biochemical evidence suggests that the etiology of
      respiratory distress syndrome is multifactorial with a significant genetic
      component. There are reports about polymorphisms and mutations on the surfactant
      protein genes, especially surfactant proteins-B, that may be associated with
      respiratory distress syndrome, acute respiratory distress syndrome, and
      congenital alveolar proteinosis. Individual differences regarding respiratory
      distress syndrome and acute respiratory distress syndrome as well as patient
      response to therapy might reflect phenotypic diversity due to genetic variation,
      in part. The study of the differences between the allelic variants of the
      surfactant protein genes can contribute to the understanding of individual
      susceptibility to the development of several pulmonary diseases. The
      identification of the polymorphisms and mutations that are indeed important for
      the pathogenesis of the diseases related to surfactant protein dysfunction,
      leading to the possibility of genotyping individuals at increased risk,
      constitutes a new research field. In the future, findings in these endeavors may
      enable more effective genetic counseling as well as the development of
      prophylactic and therapeutic strategies that would provide a real impact on the
      management of newborns with respiratory distress syndrome and other pulmonary
      diseases.

PMID- 17505705
TI  - Urinary and sexual manifestations of patients infected by HTLV-I.
AB  - HTLV-I is considered to be a virus of low morbidity, since the principal diseases
      associated with this viral infection, HTLV-I-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL), are
      observed in less than 5% of infected individuals. Urinary symptoms are frequent
      in patients with myelopathy and consist principally of nocturia, frequency,
      urgency, and urinary incontinence; however, the importance of these dysfunctions
      and their correlation with myelopathy is still to be fully clarified. This review
      gives particular emphasis to the high frequency of urinary and sexual complaints
      not only in patients with myelopathy but also in individuals considered to be
      HTLV-I carriers. Detrusor overactivity and bladder-sphincter dyssynergia are the
      most common urodynamic findings. The fact that urinary complaints and urodynamic
      parameters reported in individuals considered to be carriers are similar to those
      detected in patients with myelopathy supports the hypothesis that urinary
      disorders may represent an oligosymptomatic form of HAM/TSP. Erectile dysfunction
      is frequently observed in HTLV-I-infected patients with or without myelopathy.
      Urinary tract infections are also highly prevalent in these patients. Despite the
      lack of an effective treatment for myelopathy, the use of anticholinergic drugs
      and phosphodiesterase type 5 (PDE5) inhibitors may improve urinary complaints and
      erectile dysfunction in these patients.

PMID- 17505706
TI  - Retinal nerve fiber layer defect in a patient with healthy neuroretinal rim.

PMID- 17505707
TI  - Sepsis-associated encephalopathy as a differential diagnosis with motor deficit
      plus altered mental status.

PMID- 17505708
TI  - Portal vein aneurysm.

PMID- 17505710
TI  - [How to reward and stimulate the task of reviewing scientific articles?].

PMID- 17505711
TI  - [Use of Medpor spherical implant: analysis of 61 orbital surgeries].
AB  - PURPOSE: To analyze the use of Medpor biointegrated implant in surgeries of
      evisceration, enucleation or secondary implantation in anophthalmic sockets.
      METHODS: The Medpor orbitary implant was used in 61 surgeries. In 18 cases of
      evisceration the implant's wrapping was not necessary. In 12 enucleation and
      secondary implantation surgeries the utilized material to wrap the implant was
      homologous duramater. In the other 31 surgeries, the implant wrapping was made
      from autologous tissue (sclera, dermis, orbicular muscle or auricular cartilage),
      utilizing the "cap" technique--covering only the anterior surface of Medpor.
      RESULTS: The patients were operated from January 1998 to December 2004 with an
      average follow-up period of 30 months. In all cases the implant was well
      accepted, allowing for a good adaptation of the prosthesis. Late exposure of the
      implant occurred in two patients: the first was corrected by the replacement of
      the implant in the cavity, while in the second case the exposure was wrapped with
      a tarsus flap. CONCLUSIONS: In our experience the Medpor implant presents good
      acceptance, with a small exposure rate (only 2 cases), no infection or migration
      cases, and a good prosthesis adaptation in all patients. The use of autologous
      tissue to wrap the implant's anterior surface eliminates the inherent risk of
      using homologous tissues.

PMID- 17505712
TI  - [Simplified intraoperative adjustable suture technique for horizontal strabismus
      surgery: a study of 153 cases].
AB  - PURPOSE: To evaluate the simplified intraoperative adjustable suture technique
      for horizontal strabismus surgery. METHODS: Data charts of all patients who
      underwent horizontal strabismus surgery by the simplified intraoperative
      adjustable suture technique at the Strabismus Department of the "Hospital das
      Clinicas" of the University of Sao Paulo in the period from January 2001 to
      November 2005 were evaluated retrospectively. Using this technique, the
      adjustment was calculated based on the corneal light reflection, having
      considered the difference between the measures in the awake state and with the
      anesthetized patient. RESULTS: One hundred fifty-three patients were operated on,
      73 (47.8%) cases of esotropia (ET) and 80 (52.2%) of exotropia (XT). Under
      anesthesia, 123 (80.4%) patients had the eye position modified: 69 (56.1%) were
      less esotropic, 51 (41.5%) were more exotropic and 3 (2.4%) were less exotropic.
      Surgery was adjusted in 60 (39.2%) patients: 30 were esotropia and 30 were
      exotropia. Surgical success was defined as an eso- or exodeviation within 10
      prism diopters, in a follow-up period of at least 180 days. The overall success
      rate was 71.6%. CONCLUSIONS: The simplified intraoperative adjustable suture
      technique, described in 2003 in a study performed on 49 patients operated on by
      the same surgeon, was shown to be efficient in this larger series of patients
      operated on by different surgeons. This technique should be considered in
      patients who do not cooperate in other adjustment techniques, aiming at improved
      success rates.

PMID- 17505713
TI  - Stratus optical coherence tomography findings in patients with retinopathy of
      prematurity.
AB  - PURPOSE: To describe morphological features of the macula in patients with
      retinopathy of prematurity. METHODS: Twelve premature babies with retinopathy of
      prematurity grades I, II and III underwent dilated fundus examination and optical
      coherence tomography evaluation. RESULTS: In all thirteen eyes of the twelve
      premature patients optical coherence tomography revealed a condensed retinal
      pigmented epithelial layer in the macular-foveal area shown by increased
      reflectivity. In these eyes the retinal layers were not well differentiated.
      Foveal depression was clearly evident in 23%. CONCLUSIONS: In premature patients
      with retinopathy of prematurity, optical coherence tomography revealed poorly
      differentiated layers in the macular region with increased reflectivity in
      retinal pigmented epithelial-choriocapillaris zone.

PMID- 17505714
TI  - [Quantitative changes in tear film after refractive surgery: comparative study
      between PRK and LASIK].
AB  - PURPOSE: To compare quantitative changes induced in the tear film of patients
      submitted to photorefractive keratectomy and LASIK over a year. METHODS: A
      prospective, longitudinal, comparative, post-interventional study was designed to
      distinguish tear film changes before and one year after refractive surgery
      procedures in 48 patients submitted to PRK and 36 patients submitted to LASIK,
      using type 1 Schirmer test in the right eye and red phenol thread test in the
      left eye. RESULTS: Tear film assessment between the first and third postoperative
      month demonstrated Schirmer and phenol red measurements below basal values for
      both procedures. One year after the procedures, measurements returned to
      presurgical values. CONCLUSION: Besides momentary and within normal limit changes
      in the measurement of tear film, no complications were found in normal patients.

PMID- 17505715
TI  - [Analysis of the eye movement patterns in visual search tasks: effect of
      familiarity and stimulus features].
AB  - PURPOSE: To analyze eye movements in asymmetric visual search using the task of
      normal and mirrored position letters. To evaluate the effect of familiarity and
      stimulus features. METHODS: Eighty-three university students with normal or
      corrected-to-normal vision were asked to search for a letter in inverted position
      to the letters in a group of either normal or mirrored letters. Four types of
      letters were used (Z, N, E and G) and the eye movements were tracked by a
      specialized computer-based system (eyetracking). The analyzed measurements were:
      reaction time, fixation number and duration, saccade distance and duration.
      RESULTS: All measures varied with the type of letter. Reaction time, fixation
      number, and saccade distance were higher when the task was to find the normal
      letter in a group of mirrored letters. In this condition, fixation duration was
      smaller. Interaction was found between familiarity and the type of letter for the
      reaction time, fixation number and duration. The reaction time and fixation
      number increased together with the stimulus complexity, with a greater increase
      for the normal letter target. Fixation duration, however, decreased with the
      complexity of the stimuli and the search condition. CONCLUSIONS: Finding a
      mirrored letter among normal letters proved to be easier than the contrary. The
      letter type also affected the performance. When the context is formed of
      unfamiliar complex stimuli, the fixation duration is shorter, indicating a
      narrower span for visual processing. Therefore, a greater number of fixations
      with shorter duration are needed for the unfamiliar context while less fixations
      with greater duration are needed for the familiar context.

PMID- 17505716
TI  - [Automated perimetry in patients with primary congenital glaucoma].
AB  - PURPOSE: To identify and characterize defects using the automated perimetry test
      in patients with primary congenital glaucoma. METHODS: Automated visual fields
      and charts of 81 eyes (48 patients) with congenital glaucoma were retrospectively
      analyzed, 15 being normal eyes (group N) and 66 eyes with primary congenital
      glaucoma (group G). Eyes of group G were grouped in eyes without perimetric
      changes and with early defects, characterized by MD > -6 dB (group G I= 41 eyes),
      and eyes with mild/advanced perimetric defects characterized by MD < or = -6 dB
      (group G II= 25 eyes). MAIN OUTCOME MEASURES: reliability indices, global
      indices, GHT report, foveal threshold index and descriptive visual field defects.
      RESULTS: The majority of patients showed good reliability. In group G I, 68% had
      normal visual fields; 22% showed localized defects and 10% showed general
      reduction of sensitivity. In group G II, 56% of the visual fields showed general
      reduction of sensitivity and 44% showed localized defects. The most common
      localized change was inferior paracentral scotoma. Eyes with normal visual fields
      in group G I had foveal threshold and MD values lower than normal eyes. The
      hemifield test was normal in 68% of eyes in group G I, and was abnormal in 100%
      of eyes in group G II. CONCLUSIONS: Automated perimetry test was able to show
      typical defects of glaucoma contributing to initial evaluation and giving
      reliable parameters for the follow-up of eyes in patients with congenital
      glaucoma.

PMID- 17505717
TI  - [Evaluation of eyebrow position using angular measures].
AB  - PURPOSE: To evaluate the eyebrow position in children and elderly using angle
      measurements. METHODS: The eyebrow position was evaluated by digital images in 4
      to 6-year-old children (children group) and in patients with 50 years or more
      (elderly group), separated by age range. The images were taken in the primary
      gaze position with a Sony Lithium camera and then transferred to a MacIntosh G4
      computer and processed by the NIH 1.58 program. The eyebrow position was
      evaluated using angle measures. Comparisons were done according to age, sex and
      laterality and the data were submitted to statistical analysis. RESULTS: The
      comparison of the angular measures showed that there was a significant difference
      in the position of eyebrow position between the studied groups with the same age.
      But comparing children and elderly there were differences in all performed
      measurements. CONCLUSION: The eyebrow external angle positions showed differences
      between children and elderly with a positive association between eyebrow position
      and age.

PMID- 17505718
TI  - [In vivo confocal microscopy in amiodarone corneal deposits].
AB  - PURPOSE: To describe in vivo confocal microscopy findings in patients with
      different stages of amiodarone-induced keratopathy, and correlate biomicroscopy
      stages with confocal stages. METHODS: Twenty eyes of 10 patients (6 men and 4
      women), who receive treatment with amiodarone were selected for the study with
      confocal microscopy (MC). RESULTS: The average age was 58 +/- 6.2 years (50-66
      years) and time of use of the drug was 6 +/- 3.2 years (2-11 years). All patients
      have best correct visual acuity > or =20/40. There were two patients in stage 1,
      4 patients in stage 2 and 4 in stage 3 of induced keratopathy. All corneas
      presented brilliant intracellular inclusions with high reflectivity in the basal
      epithelium layer. Patients in stage 2 and 3 have all corneal layers affected.
      There are thinning and increase of tortuosity of corneal nerves in patients in
      stage 2 and 3. The endothelial count was 2,524 +/- 150,3 cell/mm(2). CONCLUSION:
      The basal epithelium was most affected in any of the keratopathy stages. In stage
      1 patients only the superficial and basal epithelium are affected, while patients
      in stages 2 and 3 have all corneal layers affected. With the advance of
      keratopathy the corneal nerves became thinner and tortuous.

PMID- 17505719
TI  - [Eyelash alterations in anophthalmic patients].
AB  - PURPOSE: To evaluate the eyelash alterations in anophthalmic cavity patients.
      METHODS: An observational study was done looking for eyelash alterations in
      anophthalmic cavity patients at "Faculdade de Medicina de Botucatu". RESULTS:
      Eyelash alterations were observed in 70.7% of the anophthalmic patients. The most
      frequently observed eyelash alterations were eyelash ptosis (24.4%), reduction in
      the quantity (19.5%), trichomegaly (19.5%), trichiasis (14.6%) and entropium
      (17.0%). CONCLUSION: The anophthalmic cavity patients have eyelash alteration and
      ptosis, reduction in quantity, trichomegaly, trichiasis are the most common
      observed situations. Further studies are needed to know more about it.

PMID- 17505720
TI  - [Prevalence of retinopathy of prematurity in premature babies examined during the
      period 1992-1999, Joinville (SC): evaluation of associated risks--screening].
AB  - PURPOSES: To evaluate the prevalence of retinopathy of prematurity in premature
      babies examined at the "Hospital de Olhos Sadalla Amin Ghanem", coming from the
      "Maternidade Darcy Vargas" during the period from June 1992 to June 1999. To
      describe the risk factors that cause a predisposition to develop retinopathy of
      prematurity in the "Maternidade Darcy Vargas" and criteria to improve screening.
      METHODS: 286 premature babies were selected in accordance with the predetermined
      criteria (gestation period less than 37 weeks, first examination at 4-12 week of
      age, minimum of 3 ophthalmic examinations before being 180 days old and
      registration at the "Hospital de Olhos Sadalla Amin"). An analysis of the total
      group of premature babies was carried out, being classified into Group 1 (without
      retinopathy of prematurity) and Group 2 (with retinopathy of prematurity) and the
      factors related to presence or not of retinopathy of prematurity in the premature
      babies were described. In order to evaluate the frequency of retinopathy of
      prematurity and factors associated with its occurrence, the Chi-Squared or the
      Fisher Exact tests were used. Margin of error 5%. RESULTS: 228 premature babies
      did not present sings of retinopathy of prematurity (group 1) and 58 presented
      signs (group 2). The prevalence of retinopathy of prematurity was 20%, 9% being
      in stage 1; 7% in stage 2; 4% in stage 3 and 1% in stage 4a. The most involved
      factors were: birth weight (p<0.0001), oxygen therapy (p<0.0000), birth age
      (p=0.0006), lung disease (p=0.0041), blood transfusion (p=0.0002), central
      nervous system alterations (p=0.0259), serious infections (p=0.0278) and Apgar
      less than 7 in the first minute (p=0.0442). The premature babies that most needed
      treatment weighed less than 1,399 g and were 33 weeks old. CONCLUSION: According
      to the data the prevalence of retinopathy of prematurity was 20%. The premature
      babies' risks of retinopathy of prematurity were concentrated on weight below
      1,400 g and age of 33 weeks. Bigger premature babies should be observed when one
      or more of the following factors are present: oxygen therapy, blood transfusion,
      lung disease, central nervous system alterations, serious infections and Apgar
      less than 7 in the first minute.

PMID- 17505721
TI  - [The role of senile enophthalmos in involutional entropion].
AB  - PURPOSE: To observe the role of senile enophthalmos in involutional entropion.
      METHODS: Prospective clinical study comparing a population of 30 white patients
      above 65 years with involutional entropion (Group I) of an age- and race-matched
      control group (Group II). All age and exophthalmometric values were analyzed by a
      statistical study. RESULTS: The average age was 77.7 years in Group I and 75.7
      years in Group II. Eyes with involutional entropion are no more likely to have
      enophthalmos (15.22 mm) than is the involved contralateral eye (15.11 mm) or
      normal eyes of an age- and race-matched control group (15.13 mm). CONCLUSION:
      There is no correlation between involutional entropion and senile enophthalmos.

PMID- 17505722
TI  - [Measuring the refractive power of customized soft contact lenses].
AB  - PURPOSE: Soft contact lenses with spherical base curves have been used for many
      years. The computation of the refractive powers of these lenses is easy,
      requiring only that one uses the lens maker equation for thick lenses.
      Nevertheless, for customized contact lenses, there is yet no reliable method for
      measuring the higher order optical aberrations. In this study we have developed
      in the Center for Visual Sciences of the University of Rochester an optical
      apparatus that allows for precise measurement of low and high order aberrations
      of customized soft contact lenses. METHODS: An optical apparatus was mounted on a
      conventional optical bench. This apparatus consists of a wet cell where the
      contact lenses are placed, a series of relay lenses, mirrors, beam splitters, and
      a Hartmann-Shack sensor. Bausch & Lomb manufactured the lenses used in this
      study. RESULTS: The root mean square error (RMSE) of the instrument was 0.04
      microns. Given that the RMSE of the customized lens is between 4 and 6 microns,
      i.e., the precision of the instrument is approximately 1%. This precision is more
      than sufficient for the type of measurements necessary for manufacturing
      customized contact lenses. CONCLUSION: The instrument developed is extremely
      precise for measuring high order aberrations--up to the 10th order Zernike
      polynomials, that is, up to the 66th term. This technology is important for the
      development of new methods of optical corrections for patients that usually do
      not adapt to normal sphere-cylinder spectacles or that cannot undergo refractive
      surgery, such as those which have keratoconus, for example.

PMID- 17505723
TI  - [Exposure of normal Tenon's capsule fibroblasts from pterygium to 5-fluorouracil
      and mitomycin C].
AB  - PURPOSE: To evaluate the fibroblast proliferation activity of normal Tenon's
      capsule from primary and recurrent patients with pterygium. METHODS: A randomized
      prospective study was performed with 41 normal Tenon's capsule fragments from 21
      primary and 20 recurrent patients with pterygium. The sample was collected from
      the inferior cul-de-sac. Proliferation rate from fibroblasts were evaluated after
      mitomycin C and 5-fluorouracil exposition. Data were submitted to statistical
      analysis. RESULTS: Of the 41 cultivated normal Tenon's capsules, only 1 from
      primary and 2 from recurrent pterygium patients proliferated. After antimitotic
      exposition, the proliferation rate was similar with both drugs. CONCLUSION:
      Mitomycin and 5-fluorouracil promote similar inhibition regarding proliferation
      of normal Tenon's fibroblast cultures.

PMID- 17505724
TI  - [Evaluation of corneal tissue by slit lamp and specular microscopy during the
      preservation period].
AB  - PURPOSE: To analyze changes evaluation of corneal grafts by slit lamp and
      electron microscopy examination in order to ensure a donor cornea of good quality
      level for the patient. METHODS: 203 corneas donated to the Sorocaba Eye Bank
      between September 2002 and February 2003 were prospectively evaluated. The
      evaluation was graded from 0 to 3 according to the following factors: exposure
      and epithelial damage, stromal opacity, Descemet folds, pleomorphism,
      polymegatism and guttata, endothelial snail track, edema, reflectivity. The data
      were correlated with time between death and preservation, endothelial cell count
      and donor's age. RESULTS: 203 corneas were evaluated. The mean age of donors was
      55 years (dp= 14.8 years). The mean time between death and preservation was 9.1 h
      (minimum of 2 h and maximum of 25 h). Eighty-six corneas suffered worsening of
      evaluation, whereby 66.3% had less than 2,500 endothelial cell count and 59.3%
      presented time between death and preservation over 6 hours. The mean day of the
      grading change was the 5th. CONCLUSIONS: Corneal grafts from younger donors had
      significantly better evaluation than those of older donors. The mean time of the
      evaluation change was on the 5th day in 50% of the corneas, however, an
      expressive number of corneas suffered changes on the 6th, 7th and 8th day.
      Corneal graft preserved after 6 hours of death had a greater tendency to lower
      cell count and to decrease in evaluation grades.

PMID- 17505725
TI  - [Ophthalmologic conditions of AIDS patients with long-term follow-up].
AB  - PURPOSE: To evaluate the ophthalmologic conditions of patients with AIDS, with
      long-term follow-up, previously evaluated by an ophthalmologist, considering
      general conditions related with AIDS. METHODS: Observational study of 42 patients
      with AIDS divided into two groups: Group I: 8 patients with previous AIDS-related
      cytomegalovirus retinitis, Group II: 34 patients with AIDS without
      cytomegalovirus retinitis. Each patient had been submitted to one ophthalmologic
      examination. General data of the patients were obtained from the medical records.
      RESULTS: The majority of the patients presented visual acuity in the best eye
      between logMAR 0.0 (68.3%) and 0.1 (26.9%). Optic prescription for refractive
      errors benefited 39.4% of the patients in Group II but none of the patients in
      Group I. Presbyopia was corrected in 27.3% of Group II and in 12.5% of Group I
      patients. No current ocular AIDS-related manifestations were detected in any
      group. Ocular posterior segment alterations, all of them consisting of retinitis
      / retinochoroiditis scars, were found in 10 patients, 7 (16.7%) belonging to
      Group I and 3 (7.1%) to Group II. CONCLUSION: Ten (24.4%) patients presented
      visual alteration due to age. Except for the patients presenting previous
      retinitis and retinochoroiditis, all the other patients were in good ophthalmic
      conditions and most of them were in immunologic recovery due to the use of highly
      active antiretroviral therapy.

PMID- 17505726
TI  - Flicker perimetry in healthy subjects: influence of age and gender, learning
      effect and short-term fluctuation.
AB  - PURPOSE: To determine the mean critical fusion frequency and the short-term
      fluctuation, to analyze the influence of age, gender, and the learning effect in
      healthy subjects undergoing flicker perimetry. METHODS: Study 1--95 healthy
      subjects underwent flicker perimetry once in one eye. Mean critical fusion
      frequency values were compared between genders, and the influence of age was
      evaluated using linear regression analysis. Study 2--20 healthy subjects
      underwent flicker perimetry 5 times in one eye. The first 3 sessions were
      separated by an interval of 1 to 30 days, whereas the last 3 sessions were
      performed within the same day. The first 3 sessions were used to investigate the
      presence of a learning effect, whereas the last 3 tests were used to calculate
      short-term fluctuation. RESULTS: Study 1--Linear regression analysis demonstrated
      that mean global, foveal, central, and critical fusion frequency per quadrant
      significantly decreased with age (p<0.05). There were no statistically
      significant differences in mean critical fusion frequency values between males
      and females (p>0.05), with the exception of the central area and inferonasal
      quadrant (p=0.049 and p=0.011, respectively), where the values were lower in
      females. Study 2--Mean global (p=0.014), central (p=0.008), and peripheral
      (p=0.03) critical fusion frequency were significantly lower in the first session
      compared to the second and third sessions. The mean global short-term fluctuation
      was 5.06 +/-1.13 Hz, the mean interindividual and intraindividual variabilities
      were 11.2+/-2.8% and 6.4+/-1.5%, respectively. CONCLUSION: This study suggests
      that, in healthy subjects, critical fusion frequency decreases with age, that
      flicker perimetry is associated with a learning effect, and that a moderately
      high short-term fluctuation is expected.

PMID- 17505727
TI  - Perceptual filling-in of stereoscopically presented targets.
AB  - PURPOSE: To investigate the influence of parametric variation on the filling-in
      latency of stereoscopically presented stimuli. METHODS: Anaglyphs were created
      using two circular patches of 0.3 masculine diameter, 0.5 masculine disparity and
      6 masculine eccentricity from fixation point. Targets were presented at the
      visual field midline, 90 masculine and 270 masculine positions, with crossed and
      uncrossed disparity. The time elapsed for disappearance of the target under
      voluntary steady fixation was computed. Eighteen subjects tested. RESULTS: There
      was no significant difference between crossed and uncrossed disparities, nor
      between near or far from the vertical horopter line. The significant difference
      was between upper and lower visual field positions. CONCLUSION: The results show
      that: (i) stereoscopic presentation does not influence the target filling-in
      latency; (ii) differences between dorsal and ventral visual stream might
      influence target filling-in latency.

PMID- 17505728
TI  - Influence of bromopride in the prophylaxis of nausea associated with fluorescein
      angiography.
AB  - PURPOSES: To determine the efficacy of bromopride in the prophylaxis of nausea
      during fluorescein angiography, when compared with a placebo. METHODS: The study
      was a double-masked random clinical trial, between December of 2004 and April of
      2005. Examinations were performed with 20% intravenous fluorescein sodium in a
      single dose of 2.5 ml. The patients were divided into two groups: group 1,
      patients who received a 2 ml intravenous dose of 5 mg/ml bromopride and group 2,
      patients who received a 2 ml intravenous dose of 0.9% sodium chloride (placebo),
      both 20 minutes before the dye injection. Cases of nausea were observed during
      and after the examination. RESULTS: 352 patients were enrolled, 176 in each
      group. Cases of nausea were observed in 12 (6.8%) patients of the bromopride
      group and in 11 (6.3%) patients of the placebo group (p<0.829 - relative
      risk=1.05). CONCLUSION: Bromopride did not prevent the occurrence of nausea in
      fluorescein angiography, when compared with a placebo.

PMID- 17505729
TI  - Correlation between clinical diagnosis and PCR analysis of serum, aqueous, and
      vitreous samples in patients with inflammatory eye disease.
AB  - PURPOSE: To study the applicability (sensitivity, specificity) of polymerase
      chain reaction (PCR) tests in the detection of cytomegalovirus (CMV), herpes
      virus (HSV) and varicella zoster (VZV), Epstein-Barr virus (EBV), Mycobacterium
      sp and Toxoplasma gondii in the diagnosis of patients with or without AIDS, with
      presumably infectious uveitis, using serum, aqueous humor and vitreous humor
      samples. METHODS: Twenty individuals with uveitis of presumed infectious origin
      were evaluated. Sixteen of them had AIDS, four were immunocompetent individuals.
      We also evaluated 4 normal controls who underwent vitrectomy surgery. Clinical
      evaluation of the patients was performed together by three clinicians. PCR
      evaluations of the serum, aqueous, and vitreous humor were performed in a masked
      fashion by the laboratory staff. RESULTS: Twelve patients had a clinical
      diagnosis of CMV retinitis. Of these 6 (50%) had a positive PCR for CMV in the
      vitreous, three (25%) had a positive PCR for CMV in the serum, and none were
      positive in the aqueous. Five patients had a clinical diagnosis of acute retinal
      necrosis (ARN). Three (60%) of these had positive PCR for HSV/VZV in the
      vitreous. One of these patients had a positive PCR reaction for both EBV and
      HSV/VZV in the vitreous samples. One patient with cutaneous herpes zoster had a
      positive PCR reaction for HSV/VZV in the serum. Four patients had a presumed
      diagnosis of ocular toxoplasmosis, one patient (25%) had a positive PCR for
      Toxoplasma gondii in the serum, 3 (75%) had positive results in the aqueous, and
      2 (50%) had positive results in the vitreous. One patient with presumed ocular
      tuberculosis had a positive PCR reaction both in the serum and in the vitreous
      samples. Finally, none of the four control individuals revealed any positive PCR
      reaction. CONCLUSION: PCR is an auxiliary diagnostic procedure that should be
      evaluated together with ophthalmological aspects of the patient.

PMID- 17505730
TI  - [Effects of reading, exercise and exercise combined with reading on intraocular
      pressure for patients sustaining primary glaucoma (open angle) or ocular
      hypertension, both clinically controlled with topic medication].
AB  - PURPOSE: To check intraocular pressure (IOP) in individuals using prostaglandin,
      prostamide or beta-blocker analogues, who sustain either primary open angle
      glaucoma or ocular hypertension after reading, exercise or exercise combined with
      reading. METHODS: 40 individuals (79 eyes), subdivided in to five groups: G1
      (with arterial hypertension and either glaucoma or ocular hypertension, all users
      of prostaglandin or prostamide analogues); G2 (with arterial hypertension and
      either glaucoma or ocular hypertension, all users of beta-blockers); G3 (not
      sustaining arterial hypertension but suffering from either glaucoma or ocular
      hypertension, all users of prostaglandin or prostamide analogues); G4 (not
      sustaining arterial hypertension but suffering from either glaucoma or ocular
      hypertension, all users of beta-blockers) and G5 (not sustaining arterial
      hypertension and also not suffering from either glaucoma or ocular hypertension)
      had their intraocular pressure checked before and after undergoing reading,
      exercise, and exercise combined with reading. Each type of test was conducted in
      a different day, always in the afternoon. RESULTS: No significant statistical
      difference has been noticed between the initial and final intraocular pressure
      mean in the different groups, when reading, performing exercises or exercises
      combined with reading. CONCLUSION: To read and to work out--either separately or
      jointly--does not pose an aggravating factor to the intraocular pressure of
      patients with primary open glaucoma or ocular hypertension, using prostaglandin,
      prostamide or beta-blocker analogues.

PMID- 17505731
TI  - [Adult esotropia during pregnancy: case report].
AB  - The authors report a case of a female patient who presented, for the second time,
      diplopia and acute esotropia during pregnancy. There was no trauma involved
      neither was systemic disease. The patient was treated with conventional
      occlusion, and, soon after delivery, the squint was resolved.

PMID- 17505732
TI  - [Ectodermal dysplasia, ectrodactyly and clefting syndrome: ocular manifestations
      of this syndrome in a case report].
AB  - A case of ectodermal dysplasia, ectrodactyly and clefting syndrome (EEC), a rare
      disease with an important ocular impairment and with scarce literature. Patient,
      26 years old with complaints of pain, with photophobia and low visual acuity in
      the left eye for three days. The patient was submitted to a genetic investigation
      after complete physical and ophthalmologic examinations. EEC syndrome was
      diagnosed and all systemic and ocular modifications identified. The patient
      presented a scar in the left eye, with difficulties in healing due to ocular
      damage caused by the syndrome (lack of tear film, trichiasis, Meibomius gland
      absence, among others). The ocular modifications in this rare syndrome were
      described in order to institute preventive treatment and to reduce the risks of
      low visual acuity in patients who receive this genetic diagnosis.

PMID- 17505733
TI  - [Butterfly-shaped pattern dystrophy: case report].
AB  - The authors present a case of butterfly-shaped pattern dystrophy diagnosed in a
      male patient, with retinal pigmented epithelium atrophy and central visual acuity
      decrease in one of the eyes. The evolution of this case was not benign as
      described in previous reports. A well-defined lesion located in the posterior
      pole of both eyes associated with fluorescein angiography allowed the diagnosis
      of this pattern dystrophy. Optical coherence tomography was performed, showing
      the aspects of the pathology, for the first time.

PMID- 17505734
TI  - [Bilateral acute angle closure glaucoma in a young patient receiving oral
      topiramate: case report].
AB  - This paper reports a clinical case of uveal effusion in both eyes causing
      bilateral acute angle closure glaucoma in a young patient after oral
      administration of topiramate, a new anticonvulsant medication. Rarely, some drugs
      have produced uveal effusions, forward shift of the iris-lens diaphragm,
      transient myopia and secondary angle closure glaucoma. A 40-year old white woman
      was seen at the emergency department of the "Hospital Banco de Olhos de Porto
      Alegre (RS)"--Brazil, with severe headaches and blurry vision in both eyes. Her
      medications included topiramate, started 10 days before. Slit lamp examination
      revealed conjunctival injection, chemosis and shallow anterior chambers.
      Intraocular pressure measured 40 and 38 mmHg. Fundoscopic examination findings
      were normal. Ultrasound scan was performed and demonstrated separation between
      the choroidal layer and the sclera. A diagnosis of bilateral uveal effusion
      associated with the use of oral topiramate was made. Topiramate was then
      discontinued. The patient reported symptomatic improvement by the third day after
      initial examination. Symptoms were resolved and visual acuity returned to normal.
      Topiramate may cause ciliary body edema and relaxation of zonules, which induces
      a forward shift of the lens-iris diaphragm with acute myopia and angle closure.
      As the mechanism of angle closure does not involve pupillary block, peripheral
      iridectomy and topical miotics are not useful in the treatment of this type of
      secondary angle-closure glaucoma. Drug-induced uveal effusions occur rarely. The
      patient improved after topiramate discontinuation.

PMID- 17505735
TI  - [Topographically supported customized ablation for the treatment of decentered
      laser in situ keratomileusis: report of three cases].
AB  - Three cases of decentered laser in situ keratomileusis were successfully treated
      with the topographically supported customized ablation.

PMID- 17505736
TI  - [A study of idiophatic vitreomacular traction syndrome with optical coherence
      tomography images: cases report].
AB  - PURPOSE: To evaluate the features of idiophatic vitreomacular traction syndrome
      (VMT) with ocular coherence tomography (OCT--Stratus), before and after
      vitrectomy; to identify situations where ocular coherence tomography provides
      additional information on disease morphology and pathogenesis. METHODS:
      Comparative retinal ocular coherence tomography imaging was performed in four
      patients with different stages of vitreomacular traction syndrome. RESULTS:
      Standard-resolution ocular coherence tomography Stratus provides vitreous-retinal
      images that help the management and treatment of vitreomacular traction syndrome.
      CONCLUSIONS: Standard-resolution ocular coherence tomography allows good
      visualization of the architectural morphology of the vitreous and retina in
      vitreomacular traction syndrome. It helps understanding its pathogenesis,
      planning its treatment, clinical or surgical, and evaluating retinal structural
      alterations after surgery.

PMID- 17505737
TI  - [Congenital ectropion: three case reports and literature review].
AB  - To report 3 cases of congenital ectropion because of their rarity and confusing
      classification. Case 1: JPT, 2 days old, male, negro. Left upper eyelid eversion
      with chemosis was present, passive to mechanic reduction. Compressive occlusion
      was done with ectropion regression in 48 hours. Case 2: AJL, 6 years old, female,
      Caucasian, with Down syndrome. The left eye had hyperemia, lagophthalmos and
      inferior leucoma. She received horizontal shortening (superior and inferior
      tarsal strip) and skin grafts, and after 2 months the patient did not return.
      Case 3: GSD, 4 years old, male, Caucasian, with Down syndrome. His signs and
      treatment were the same as in case 2. According to Pico's classification the
      first case is classified as grade II due to eyelid eversion during the passage
      through the birth canal, more frequent in black people. Cases 2 and 3 represent
      grade III that is due to eyelid skin alteration, and the association with Down
      syndrome is observed. Treatment for ectropion grade III is always surgical, as it
      was done in these cases. We do not agree with Pico's classification, the only one
      found in medline, because there are no articles confirming the existence of grade
      I (absent tarsus), grade II should be called congenital upper eyelid eversion,
      grade IV (microphthalmos and orbital cyst) is a disease of the orbit. Grade III
      refers to true ectropion, because horizontal enlargement of superior and inferior
      eyelids (megaloblepharon).

PMID- 17505738
TI  - An unusual chiasmal visual defect in a patient with neuromyelitis optica: case
      report.
AB  - PURPOSE: To report the unusual visual field finding due to a chiasmal neuritis in
      a 33-year-old female with the diagnosis of optic neuromyelitis optica (Devic's
      syndrome). METHODS: We report a case of a 33 years old female with limb
      paraesthesias, weakness in the legs, bowel and bladder dysfunction that was
      referred to the "Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
      da Universidade de Sao Paulo" in October 1995. Six years and four months later
      she had an acute visual involvement. Ophthalmologic examination, laboratory
      studies, magnetic resonance imaging (MRI) and a 24-2 threshold visual field in
      the Humphrey field analyzer were performed. RESULTS: The MRI scan showed
      enlargement and cavitation on the spinal cord and chiasmal involvement
      (thickening of the chiasm with contrast enhancement) and no demyelinating lesions
      in the brain, brainstem, or cerebellum. The central 24-degree threshold field
      examination showed an inferior visual field defect bitemporally, disclosing a
      chiasmal involvement. CONCLUSION: Chiasmal involvement may occur in neuromyelitis
      optica, probably due to a plaque within the chiasm. The authors call attention to
      the importance of visual field examination with particular regard to quantifying
      the visual impairment and follow-up of these patients.

PMID- 17505739
TI  - Toxoplasmosis retinochoroiditis after photodynamic therapy and intravitreal
      triamcinolone for a supposed choroidal neovascularization: a case report.
AB  - The purpose is to report a complication after photodynamic therapy (PDT) and
      intravitreal triamcinolone for a presumed choroidal neovascularization in age
      related macular degeneration. Photodynamic therapy and intravitreal triamcinolone
      were used in an 84-year-old man with choroidal neovascularization in the left
      eye. Forty-five days after therapy, the patient returned with a severe
      necrotizing uveitis in the posterior pole and vitritis. Laboratory investigation
      disclosed a high anti-Toxoplasma IgG titer. Therapy with pyrimethamine,
      sulfadiazine and folinic acid resulted in total lesion healing although central
      vision was lost. Intravitreal triamcinolone may have had an influence on the
      exacerbation of retinochoroiditis in the posterior pole of the patient. Although
      rare, this complication may not be disregarded in the cases that require
      intraocular corticosteroids for treatment of several conditions, especially in
      patients who had previously suffered from toxoplasmosis infection.

PMID- 17505740
TI  - [Congenital retinal macrovessel: case report].
AB  - The authors report a case of arteriolar retinal macrovessel, diagnosed by routine
      ophthalmologic examination, as well as its optic coherence tomography aspects.
      Congenital retinal macrovessel is a large aberrant vessel, often unilateral,
      usually a vein, rarely an artery, located in the posterior pole which can cross
      the fovea and median raphe.

PMID- 17505741
TI  - [LASIK interface fluid accumulation caused by glaucoma associated with herpetic
      keratouveitis: case report].
AB  - Herpes simplex virus infection is a frequent cause of intraocular inflammation or
      anterior uveitis. Ocular hypertension is a common feature in herpetic
      keratouveitis. We describe a fluid accumulation and flap displacement in late
      postoperative period (28 months) of LASIK associated with ocular hypertension
      caused by herpetic keratouveitis. This finding supports the theory that flap
      attachment after LASIK is only partial and the virtual space remains
      indefinitely. The presence of ocular hypertension may lead to corneal edema and
      fluid accumulation in the interface.

PMID- 17505742
TI  - Alcohol-related massive eyelid swelling: case report.
AB  - Alcohol-related massive eyelid edema has been rarely reported. The differential
      diagnosis includes local and systemic conditions. Alcohol itself can be
      associated with dermatological hypersensitivity reactions, appearing soon after
      alcoholic drinks. Massive bilateral eyelid swelling can constitute diagnostic
      pitfalls and therapeutic challenges to general practitioners with a placebo.

PMID- 17505743
TI  - [Drug delivery systems for the posterior segment of the eye: fundamental basis
      and applications].
AB  - The diseases of the posterior segment of the eye are responsible for most cases
      of irreversible blindness worldwide. These conditions stimulate the development
      of new modalities of treatment for vitreoretinal diseases. The success in the
      treatment aims, mainly, the delivery of effective doses of pharmacological agents
      directly to the target sites. Because of the difficulties in delivering drugs to
      the posterior segment of the eye, the development of intraocular delivery systems
      that allow the delivery of therapeutic concentrations of drugs for long periods
      are being studied. These systems offer many advantages, such as increase in drug
      bioavailability, obtaining constant and sustained drug release, to achievement of
      elevated local concentrations of drugs without systemic side effects, targeting
      one specific tissue or cell type, reducing the frequency of intraocular
      injections. These advantages can increase the comfort of the patient and reduce
      the complications observed with intraocular injections. Several drug delivery
      systems are being developed with the above described purposes. These systems may
      be prepared with biodegradable or non-biodegradable polymers or they may be lipid
      formulations. The drug delivery systems are represented, mainly, by micro- e
      nanoparticles and implants, composed of different polymers; by liposomes, which
      are made of lipids and surfactants; and by iontophoresis, that is based on the
      application of an electric current. In this review, the main characteristics of
      the different drug delivery systems will be shown, with their potentialities of
      clinical application.

PMID- 17505744
TI  - Seasonal variations in spatial usage by the estuarine dolphin, Sotalia guianensis
      (van Beneden, 1864) (Cetacea; Delphinidae) at its southern limit of distribution.
AB  - The use of space by the resident population of estuarine dolphins (Sotalia
      guianensis) in Norte Bay, southern Brazil was studied by boat surveys between
      2000 and 2003. Data such as the geographical position and group size was
      collected at 5-minute intervals using focal-group sampling. The distribution and
      seasonal and daily group home-ranges were estimated using a GIS (Geographic
      Information System) environment. The dolphins did not use the area homogeneously,
      restricting their activities to a well-defined area located in the western part
      of the bay, while the use of the eastern part was not observed. A discrepancy
      between the Environment Protection Area of Anhatomirim, created especially to
      protect this population and the distribution of the dolphins was observed.
      Seasonal group home-range varied both qualitatively and quantitatively among the
      four consecutive seasons analyzed. The dolphins tended to use a larger area in
      cold seasons, when apparently the abundance of major prey items is lower. Core
      areas of intense use were identified, and also varied seasonally. These core
      areas may be regarded as critical habitats and require special legislation and
      control. The mean daily group home-range did not differ statistically among
      seasons. The present study corroborates a spatially strict residency pattern of
      the estuarine dolphin in highly productive coastal ecosystems.

PMID- 17505745
TI  - The small-scale urban reservoir fisheries of Lago Paranoa, Brasilia, DF, Brazil.
AB  - In many cases in large urban centers, which have appropriate waterbodies, small
      scale fisheries are the only source of cheap protein for the poor. In Lago
      Paranoa, located in Brasilia, the capital city of Brazil, fishing was studied by
      conducting interviews with 53 fishers filling in logbooks from March, 1999 to
      March, 2000 in three fishing communities. The fishers come from the poorest towns
      around Brasilia, known as satellite-towns. They have been living there on average
      for 21.7 years (s = 9.6 years), their families have 4.9 members (s = 3.6) on
      average and 44.2% do not have a basic education. However, such characteristics
      are similar to the socioeconomic indices of the metropolis where they live. In
      spite of being illegal between 1966 and 2000, fishing generated an average
      monthly income of U 239.00 dollars (s = U 171.77 dollars). The Nile Tilapia
      Oreocrhromis niloticus is the main captured species (85% of a total number of
      landings in weight of 62.5 t.). Fishing is carried out in rowing boats,
      individually or in pairs. The fishing equipment used are gillnets and castnets.
      Gillnets were used actively, whereby the surface of the water is beaten with a
      stick to drive Tilapias towards nets as they have the ability to swim backwards.
      This fishing strategy was used in 64.7% of the fisheries, followed by castnets
      (31.1%) and by gillnets which were used less (4.2%). The fish is sold directly in
      the streets and fairs of the satellite-towns to middlemen or to bar owners. Three
      communities have different strategies in terms of fishing equipments, fishing
      spots and commercialization. Consequently, there are statistically significant
      differences in relation to the monthly income for each one of these communities.

PMID- 17505746
TI  - Anthropic effects on the fish community of Ribeirao Claro, Rio Claro, SP, Brazil.
AB  - The effect of anthropic alterations such as drain discharge on a fish community
      was studied in the Ribeirao Claro River, municipality of Rio Claro, State of Sao
      Paulo, southeastern Brazil. Samples were made monthly in three different points
      along the river (headwaters, mid course, and confluence) between December, 2003
      and March, 2004, which is the reproductive period for the majority of the
      species. The fish community of the Ribeirao Claro River showed a fair composition
      and diversity, with species rarely observed in studies made in the region, such
      as Paravandellia oxyfera and Callichthys callichthys. Indices of diversity and
      equitability showed different results when weight or the number of individuals
      were considered. Moreover, these indices did not reveal the typical increase in
      diversity from the headwaters toward the confluence, nor the loss of richness in
      the part altered by drain discharge. An interpretation should be made with
      caution, taking into account the diverse factors included in the computation.
      Similar to the diversity indices, the Morisita-Horn similarity index did not
      reveal a great difference in the fish community of the confluence of the river,
      mainly in relation to its mid course. The decline of species richness and trophic
      composition alteration in the disturbed part is clear, which shows a great
      dominance of piscivorous species.

PMID- 17505747
TI  - Are there co-occurrence patterns that structure snake communities in Central
      Brazil?
AB  - The main factors that structure Neotropical animal communities have been the
      subject of discussion in ecology communities. We used a set of null models to
      investigate the existence of structure in snake communities from the Cerrado in
      Central Brazil in relation to the co-occurrence of species and guilds concerning
      specific resources. We used fragments (conservation units) inside the Distrito
      Federal and neighbor municipalities. In spite of recent human colonization in the
      region from the end of the 1950s, intense habitat modification and fragmentation
      has taken place. Sixty three snake species are present in the Distrito Federal.
      Co-occurrence analysis of species and guilds associated to snake diets and
      habitats suggested a lack of organization. The homogeneity of habitats in Central
      Brazil and the minor importance of ecological effects can lead to random
      arrangement.

PMID- 17505748
TI  - Niche differences between two sympatric whiptail lizards (Cnemidophorus
      abaetensis and C. ocellifer, Teiidae) in the restinga habitat of northeastern
      Brazil.
AB  - Differences among sympatric lizard species usually result from differences in the
      use of three resources: space, time and food or some combination of these three.
      However, differences in resource utilization among sympatric species may simply
      reflect their specific ecological needs rather than competitive pressures. In
      this study, we analyzed the temporal, spatial and food niche of two congeneric
      teiids (Cnemidophorus abaetensis and C. ocellifer) living sympatrically in the
      "restinga" habitat of Abaete in the Salvador Municipality, Bahia State, Brazil to
      assess the degree of niche differentiation among them. The whiptail species
      overlapped considerably in an hourly activity (Ojk = 0.93), in microhabitat use
      (Ojk = 0.97) and in the prey items consumed (Ojk = 0.89). Differences in amount
      of vegetation in the microhabitats used by both lizard species may have
      contributed to differences in the activity period and in the distribution of the
      main prey eaten by these lizards which may, in turn, facilitate their coexistence
      in Abaete. Although sympatric C. ocellifer and C. abaetensis in Abaete differed
      only slightly in their use of microhabitats, period of activity and diet, the
      most important niche dimension segregating the two species seemed to be the food
      niche.

PMID- 17505749
TI  - Responses of Chironomidae (Diptera; Insecta) to the exclusion of shrimps and
      Ephemeroptera in a coastal forest stream, Rio de Janeiro, Brazil.
AB  - In a benthic community on a continuous flat granite substrate in a third-order
      coastal forest stream, the dominant chironomid (Cricotopus) increased in number
      when shrimps (Macrobrachium olfersi and Potimirim glabra) and baetid
      ephemeropterans were excluded by electricity. The response appeared to be
      mediated by an increase in periphyton and sediments, rather than a reduction of
      direct predation or interference. Chironomids, periphyton and sediments decreased
      significantly compared to the control when shrimps only were excluded. Baetid
      ephemeropteran appeared to be the most important determinants of periphyton and
      sediment mass; the density of chironomids appeared to follow the quantity of
      periphyton and sediments.

PMID- 17505750
TI  - Abundance and diversity of phytoplankton in the Parana River (Argentina) 220 km
      downstream of the Yacyreta reservoir.
AB  - Patterns in the temporal composition, abundance and diversity of the
      phytoplankton community of the Parana river prior to and after the initial
      filling phase of the Yacyreta reservoir are analyzed. The study site is located
      220 km downstream from the Yacyreta reservoir and 30 km downstream from the
      confluence with the Paraguay river. Because both rivers remain separate and
      unmixed at the study site, we compared the possible effects of the impoundment on
      both river banks (left and right banks) in hydrological periods with similar
      duration and magnitude of the low and high water phases. Physical and chemical
      conditions measured on the right bank (water from the Paraguay river) were
      similar at both periods (pre and post-impoundment) whereas conductivity, pH and
      orthophosphate concentration increased on the left bank (water from the High
      Parana river and Yacyreta reservoir) after the impoundment. Changes in
      phytoplankton density and diversity were observed only in samples collected from
      water flowing from the reservoir (left bank). The density of Chlorophyceae
      (Chloromonas acidophila, Chlamydomonas leptobasis, Choricystis minor, Chlorella
      vulgaris, Scenedesmus ecornis, Monoraphidium minutum, M. contortum and M.
      pusillum) and Cryptophyceae (Rhodomonas minuta, Cryptomonas marssonii and C.
      ovata) increased while Cyanophyceae (Cylindrospermopsis raciborskii, Raphidiopsis
      mediterranea and Planktolyngbya subtilis) and Bacillariophyceae (Aulacoseira
      granulata and its bioforms) decreased compared to previous studies conducted on
      the left bank of the Parana river. Phytoplankton collected from the right bank of
      the river did not differ in pre and post- impoundment samples because they
      originate from the Paraguay river, which remains relatively unaffected by human
      activities.

PMID- 17505751
TI  - Food partitioning between breeding White-tailed Kites (Elanus leucurus; Aves;
      Accipitridae) and Barn Owls (Tyto alba; Aves; Tytonidae) in southern Brazil.
AB  - I examined the diet of breeding White-tailed Kites (Elanus leucurus; Aves;
      Accipitridae) and Barn Owls (Tyto alba; Aves; Tytonidae) in an agrarian area of
      southern Brazil by analyzing regurgitated prey remains. The objective was to
      evaluate how these raptors, which differ markedly in their hunting activity
      periods (owls are nocturnal and kites diurnal), share their mammalian food
      component. 2,087 prey consumed by Barn Owls and 1,276 by White-tailed Kites were
      identified. They presented a high overlap of food-niches (Piankas index was
      0.98). Based on the daily activity period of their main small mammal prey, a
      lower overlap would be expected. The crepuscular/nocturnal Mus musculus was the
      main prey for the diet of breeding Barn Owls (81%) and White-tailed Kites (63%).
      This small exotic rodent provided 63% of the small mammal biomass ingested by
      owls and 44% by kites. Larger native small mammals were also considered important
      for the diet of kites, mainly because of their biomass contribution. Although
      these raptors differ markedly in their hunting activity periods, Barn Owls and
      White-tailed Kites are very similar predators in southern Brazil, overlapping
      their diets.

PMID- 17505752
TI  - Sewage input effects on the macroinvertebrate community associated to Typha
      domingensis Pers in a coastal lagoon in southeastern Brazil.
AB  - This study was carried out at Imboassica Lagoon, located in an urban zone in the
      municipality of Macae, Rio de Janeiro state, Brazil. This lagoon has been subject
      to anthropogenic impacts due to the increasing city population, such as the input
      of sewage. Areas of variable degree of anthropogenic influence in the lagoon were
      compared regarding the structure of the macroinvertebrate community associated to
      Typha domingensis leaves. For sampling, we used 35 x 20 cm net plastic bags, with
      6.8 mm mesh containing T. domingensis leaves for colonization. Two different
      sampling stations were selected: station A, under direct input of sewage; and
      station B with lesser sewage influence. The bags were removed after 20, 40 and 75
      days of colonization. For each sample the Shannon-Wiever Diversity, Pielou
      Evenness, Jaccard Similarity Indices, Correspondence Analysis and taxonomic
      richness were calculated. A total of 31,874 individuals were sampled, belonging
      to 34 taxa. The main taxonomical groups were: Oligochaeta (41%), Chironomidae
      (40%), Ancylidae (4.6%), Polymitarcyidae (4%) and Thiaridae (3%). At station A,
      the taxonomic richness, the Evenness and Diversity values were lower than in
      station B. On the other hand, the total density was three times higher in station
      A than in B. It was already possible to discriminate the community structure of
      each sampling station in the first sampling. Trichoptera and Ephemeroptera were
      the main exclusive groups of station B and are considered good water quality
      indicators due to their high sensibility to contamination. The major contribution
      to discriminate between the macroinvertebrate communities of the two sample
      stations came from Chironomidae, Oligochaeta and Ephemeroptera.

PMID- 17505753
TI  - Sustainable harvest of two large predatory catfish in the Cuiaba river basin,
      northern Pantanal, Brazil.
AB  - Fishery is an important economic activity in the Pantanal. Among the regions
      species, the Pimelodidae catfish stands out as an important part of the annual
      catch. This study assesses the structure, exploitation and stock management of
      Hemisorubim platyrhynchos and Sorubim cf. lima, the sixth and seventh largest
      Pimelodidae of the Pantanal. The analysis is based on fish caught by commercial
      fishing in the Cuiaba river and landed at the "Antonio Moyses Nadaf" Market in
      the Cuiaba city, Mato Grosso state, Brazil. The findings indicate that commercial
      fishing activities target several fish cohorts and that usually only individuals
      above mean length at first maturation are caught. Estimates of the instantaneous
      mortality coefficient show that the current fishing mortality is low. Simulations
      of relative yield-per-recruit model demonstrate that the current yield of two
      species could be greater if the fishery effort were increased, indicating that
      the stocks are underexploited. However, an increase in current fishery efforts
      should be viewed with caution, since the stock-recruitment relationship for the
      species is unknown. The results indicate that the current harvest of two species
      in the Cuiaba River Basin is sustainable.

PMID- 17505754
TI  - Performance consequences of food mixing in two passion vine leaf-footed bugs,
      Holymenia clavigera (Herbst, 1784) and Anisoscelis foliacea marginella (Dallas,
      1852) (Hemiptera; Coreidae).
AB  - Holymenia clavigera (Herbst) and Anisoscelis foliacea marginella (Dallas)
      (Hemiptera: Coreidae: Anisoscelini) are distributed in southern Brazil and use
      various passion vine species (Passifloraceae) as host-plants. Preliminary
      observations indicate a high coexistence of these species in terms of host-plant
      use; in addition, there is a strong similarity regarding egg and nymph
      morphology. In this study, the most suitable feeding sites for nymph performance
      on wild (Passiflora suberosa Linnaeus and Passiflora misera Humbold, Bonpland et
      Kunth) and cultivated (Passiflora edulis Sims) hosts were determined by rearing
      them on each host and on the combination of hosts. Performance was determined by
      evaluating nymph development and survivorship, and adult size at emergence. Plant
      parts used were also recorded. For both species, P. suberosa was the most
      suitable host plant. First instar nymphs of both species fed on terminal buds
      more frequently when compared to other plant parts. Second instar nymphs switched
      to green fruits, whose behavior was more pronounced for H. clavigera. Thus, H.
      clavigera and A. foliacea marginella immatures are extremely similar in terms of
      host-plant use and consequences for performance, in addition to their
      morphological similarity. We suggest that these coreids may have evolved through
      several processes, including parsimony between the immature stages after
      speciation, evolutionary convergence, mimicry or genetic drift.

PMID- 17505755
TI  - Gnathopleura quadridentata Wharton, 1986 (Hymenoptera; Braconidae; Alysiinae) and
      their hosts collected in different substrates in Caldas Novas, Goias.

PMID- 17505756
TI  - Thermolysin in human cultured keratinocyte isolation.
AB  - BACKGROUND: When treating extensively burned patients using cultured epidermal
      sheets, the main problem is the time required for its production. Conventional
      keratinocyte isolation is usually done using Trypsin. We used a modification of
      the conventional isolation method in order to improve this process and increase
      the number of colonies from the isolated epidermal cell population. PURPOSE: To
      compare the action of trypsin and thermolysin in the keratinocyte isolation using
      newborn foreskin. METHODS: This method used thermolysin as it selectively digests
      the dermo-epidermal junction. After dermis separation, the epidermis was digested
      by trypsin in order to obtain a cell suspension. RESULTS: Compared to the
      conventional procedure, these experiments demonstrated that in the thermolysin
      group, the epidermis was easily detached from the dermis, there was no fibroblast
      contamination and there were a larger number of keratinocyte colonies which had a
      significant statistical difference. CONCLUSION: The number of colonies in the
      thermolysin group was significantly greater than in the trypsin group.

PMID- 17505757
TI  - Effect of zinc and benzene on respiration and excretion of mussel larvae (Perna
      perna) (Linnaeus, 1758) (Mollusca; Bivalvia).
AB  - The presence of pollutants in the ocean may affect different physiological
      parameters of animals. Oxygen consumption and ammonia excretion were evaluated in
      D-shaped larvae of mussels (Perna perna) exposed to zinc sulphate (ZnSO(4)) and
      benzene (C(6)H(6)). When compared to the control group, both pollutants presented
      a significant reduction in oxygen consumption. A reduction in the ammonia
      excretion was also observed, both for ZnSO(4) and C(6)H(6) and also in the oxygen
      consumption. The results indicate that anaerobic metabolism may occur at the
      beginning of P. perna mussels development, as observed in veliger larvae. The O:N
      ratio under experimental conditions showed low values indicating that catabolism
      in veliger larvae was predominantly proteic.

PMID- 17505758
TI  - Alternative methodology for isolation of biosurfactant-producing bacteria.
AB  - Wide biosurfactant application on biorremediation is limited by its high
      production cost. The search for cheaper biossurfactant production alternatives
      has guided our study. The use of selective media containing sucrose (10 g x L(
      1)) and Arabian Light oil (2 g x L(-1)) as carbon sources showed to be effective
      to screen and maintain biosurfactant-producing consortia isolated from mangrove
      hydrocarbon-contaminated sediment. The biosurfactant production was assayed by
      kerosene, gasoline and Arabian Light Emulsification activity and the bacterial
      growth curve was determined by bacterial quantification. The parameters analyzed
      for biosurfactant production were the growth curve, salinity concentration, flask
      shape and oxygenation. All bacteria consortia screened were able to emulsify the
      petroleum derivatives tested. Biosurfactant production increased according to the
      incubation time; however the type of emulsification (non-aqueous phase or aqueous
      phase) did not change with time but with the compound tested. The methodology was
      able to isolate biosurfactant-producing consortia from superficial mangrove
      sediment contaminated by petroleum hydrocarbons and was recommended for selection
      of biosurfactant producing bacteria in tropical countries with low financial
      resources.

PMID- 17505759
TI  - Diet of Physalaemus cf. cicada (Leptodactylidae) and Bufo granulosus (Bufonidae)
      in a semideciduous forest.
AB  - We determined the diet of the two most abundant anuran species which occur in the
      litter of a semideciduous forest (Lencois, Bahia, Brazil), Physalaemus cf. cicada
      and Bufo granulosus in the dry and rainy seasons. Pitfall traps were used to
      collect anuran and invertebrate fauna, which showed the availability of prey in
      the environment. Physalaemus cf. cicada was present in both seasons and Bufo
      granulosus only in the rainy season. Both species fed mainly on Isoptera and
      Formicidae. However, there is a difference between the rainy and dry seasons
      concerning the diet of P. cf. cicada. During the rainy season P. cf. cicada
      consumed less Isoptera and more Formicidae than in the dry season. In the
      volumetric sense, Orthoptera was the most important alimentary category for P.
      cf. cicada and B. granulosus. The Jacobs electivity index indicated that
      Physalaemus cf. cicada and Bufo granulosus were specialists in Isoptera.

PMID- 17505760
TI  - Foraging behavior of Melipona rufiventris Lepeletier (Apinae; Meliponini) in
      Ubatuba, SP, Brazil.
AB  - This study describes how the foraging activity of Melipona rufiventris is
      influenced by the environment and/or by the state of a colony. Two colonies were
      studied in Ubatuba, SP (44 degrees 48 W and 23 degrees 22 S) from July/2000 to
      June/2001. These colonies were classified as strong (Colony 1) and intermediate
      (Colony 2) according to their general conditions: population and brood comb size
      and number of food pots. The bees were active from dawn to dusk. The number of
      pollen loads presented a positive correlation with relative humidity (r(s) =
      0.401; p <0.01) and was highest between 70 and 90%. However, it was negatively
      correlated with temperature (r(s) = -0.228; p <0.01) showing a peak between 18
      and 23 degrees C. The number of nectar loads presented a positive correlation
      with temperature (r(s) = 0.244; p <0.01) and light intensity (r(s) = 0.414; p
      <0.01); it was greater between 50 and 90% of relative humidity and 20 and 30
      degrees C of temperature. They collected more nectar than pollen throughout the
      day, and were more active between 6 and 9 hours. Workers from Colony 1 (strong)
      collected nectar in greater amounts and earlier than those from Colony 2
      (intermediate). The number of pollen, nectar and resin loads varied considerably
      between the study days. Peaks of pollen collection occurred earlier in months
      with longer days and in a hotter and more humid climate. The foraging behavior of
      M. rufiventris is probably affected by the state of the colony and by
      environmental conditions, notably temperature, relative humidity, light intensity
      and length of the day.

PMID- 17505761
TI  - Prolonged use of the food dye tartrazine (FD&C yellow no 5) and its effects on
      the gastric mucosa of Wistar rats.
AB  - Tartrazine is one of the most widely used artificial foods, drugs and cosmetic
      dyes. It is a nitrous derivative and is known to cause allergic reactions such as
      asthma and urticaria, as well as having been the focus of studies on mutagenesis
      and carcinogenesis due to its transformation into aromatic amine sulfanilic acid
      after being metabolized by the gastrointestinal microflora. 45 male Wistar rats
      were assigned to a control group (A) or a treatment one (B). The treatment group
      received 7.5 mg x kg(-1) x day(-1) of tartrazine daily in drinking water offered
      ad libitum for ten months from weaning to the age of twelve months. There was a
      significant increase in the number of lymphocytes and eosinophils of the gastric
      antrum mucosa. No carcinogenetic changes in any gastric area were observed during
      the study. As tartrazine belongs to the azo class, it is still a possible food
      carcinogen. Other studies with different doses and schedules, observing their
      effects associated to other carcinogens should be carried out if their safe use
      is to be recommended.

PMID- 17505762
TI  - Chemical modulation on heterogeneous growth in Prochilodus lineatus
      (Valenciennes, 1847) (Pisces; Characiformes).
AB  - In the present study, the effect of chemical factors released by conspecifics on
      growth variability (heterogeneous growth - HetG) in a gregarious fish species
      (Prochilodus lineatus) was tested. HetG was assessed by the weight variation
      coefficient in two consecutive 21-day periods. The fish were grouped in tanks (4
      fish in each) that received running water with constant draining. The tanks
      contained either conspecifics (C) or non-conspecifics (N). Four conditions were
      established in accordance with the tank water supply: a) water with previous
      contact with conspecifics throughout the experiment (CC); b) water without
      previous contact with conspecifics throughout the experiment (NN); c) water with
      previous contact with conspecifics in just the first period, 0 to 21 days (CN);
      and d) just in the period from 21 to 42 days (NC). At the end of the experiments,
      the occurrence of chemical modulation on the growth variability in P. lineatus
      was verified: the fish that received water with previous contact with a
      conspecific (C) presented exacerbation of HetG. This corroborates the notion that
      the predominant mechanism in the determination of intraspecific growth variation
      in the gregarious species is associated to chemical factors released by
      conspecifics.

PMID- 17505763
TI  - Genetic diversity and relatedness within and between species of the genus
      Oligoryzomys (Rodentia; Sigmodontinae).
AB  - A RAPD analysis on six species of the rodent genus Oligoryzomys trapped in a wide
      area (ranging from 01 degrees N to 32 degrees S) of Brazilian territory was
      performed in order to determine the levels of genetic variability within and
      between its populations and species. One-hundred and ninety-three animals were
      collected in 13 different sites (corresponding to 17 samples) located at Pampas,
      Atlantic Rain Forest, Cerrado, and Amazon domains. Oligoryzomys sp., O. nigripes
      (8 populations), O. flavescens (4 populations), O. moojeni, O. stramineus, and O.
      fornesi were the taxa analyzed. Of the 20 primers tested, 4 generated a total of
      75 polymorphic products simultaneously amplified in 151 specimens. Various
      diversity estimators analyzed showed considerable differences between species and
      populations, indicating a great genetic variation occurring in the Oligoryzomys
      taxa investigated. A cluster analysis was made using Nei's standard genetic
      distances, however, it did not correlate the genetic heterogeneity of the species
      and populations with the geographical areas.

PMID- 17505764
TI  - Mating system of the Amazonian cichlid angel fish, Pterophyllum scalare.
AB  - The species, Pterophyllum scalare distinguishes itself by its breeding behavior,
      involving competition for territory, sexual partners, courtship and parental
      care. The purpose of this study was to identify the mating system adopted by this
      species of fish. Twenty males and twenty females were observed under semi-natural
      and experimental conditions to test the hypothesis of serial monogamy. Under semi
      natural conditions, after the third breeding cycle, the couples changed mates.
      Under experimental conditions, the couples changed partners after the first
      breeding cycle. Under experimental conditions, mate recognition was investigated
      through the preference of the females, indicated by the time they spent with the
      males. The females were available or not for courtship from new males, depending
      on their aggressiveness or submission. The larger and more aggressive males
      obtained new mating opportunities while the submissive males were rejected by the
      females. The mated fish were aggressive towards intruders in the presence of the
      mate, protecting their pair bond. In the interval between breeding cycles, the
      couples did not display aggression towards intruders, confirming the hypothesis
      of serial monogamy. Best mate selection by the females and the opportunity of new
      matings for both sexes influenced the reproductive success of this species.

PMID- 17505765
TI  - Behavioral and neuropharmacological evidence that serotonin crosses the blood
      brain barrier in Coturnix japonica (Galliformes; Aves).
AB  - This study was carried out aiming to reach behavioral and neuropharmacological
      evidence of the permeability of the blood-brain barrier (BBB) to serotonin
      systemically administered in quails. Serotonin injected by a parenteral route
      (250-1000 microg x kg(-1), sc) elicited a sequence of behavioral events concerned
      with a sleeping-like state. Sleeping-like behaviors began with feather bristling,
      rapid oral movements, blinking and finally crouching and closure of the eyes.
      Previous administration of 5-HT2C antagonist, LY53857 (3 mg x kg(-1), sc) reduced
      the episodes of feather bristling and rapid oral movements significantly but
      without altering the frequency of blinking and closure of the eyes. Treatment
      with the 5-HT2A/2C antagonist, ketanserin (3 mg x kg(-1), sc) did not affect any
      of the responses evoked by the serotonin. Quipazine (5 mg x kg(-1), sc) a 5
      HT2A/2C/3 agonist induced intense hypomotility, long periods of yawning-like and
      sleeping-like states. Previous ketanserin suppressed gaping responses and reduced
      hypomotility, rapid oral movements and bristling but was ineffective for
      remaining responses induced by quipazine. Results showed that unlike mammals,
      serotonin permeates the BBB and activates hypnogenic mechanisms in quails.
      Studies using serotoninergic agonist and antagonists have disclosed that among
      the actions of the serotonin, feather bristling, rapid oral movements and yawning
      like state originated from activation of 5-HT2 receptors while blinking and
      closure of the eyes possibly require other subtypes of receptors.

PMID- 17505766
TI  - Biological aspects of Hylesia metapyrrha (Lepidoptera; Saturniidae;
      Hemileucinae), in laboratory.
AB  - The aim of this work was to study biological aspects and the life cycle of
      Hylesia Metapyrrha in a laboratory. Laboratorial breeding was made at 25 +/- 1
      degrees C, 70 +/- 10% UR and 14 hours of photophase, feeding the larvae with
      guava leaves (Psidium guayava L. - Myrtaceae). Time was evaluated on the days of
      all the development stages; morphometry was evaluated in millimeters and the
      pupas mass in grams. The eggs were disposed in groups and covered by urticating
      abdominal hair. The incubation period lasted 52 days. The larvae, with gregarious
      habits, presented background black coloration, yellowish scoli and two orange
      longitudinal lines above and below the spiracles, during the development which
      lasted an average period of 74.59 days and went through seven instars. The pre
      pupa and the pupa stages lasted on average 8.82 and 50.56 days, respectively; the
      female pupae presented a duration, weight and size which was significantly
      bigger. The adult stage lasted on average 5.50 days with periods of pre, post and
      oviposition of 2.30, 1.90 and 1.00 days, respectively. This study broadens the
      knowledge of the immature stages, biological, morphological and behavioral
      aspects, until then restricted to the morphology and to registers of the
      occurrence of the adult forms.

PMID- 17505767
TI  - Small mammal populations of an agroecosystem in the Atlantic Forest domain,
      southeastern Brazil.
AB  - This study reports 2 years of the population dynamics and reproduction of a small
      mammal community using the removal method. The study was conducted in a rural
      area of the Atlantic Forest, in Sumidouro, Rio de Janeiro State, Brazil. The
      population sizes, age structure and reproduction were studied for the four most
      common species in the study area. The overall diversity was 1.67 and ranged
      between 0.8 to 1.67. The species richness was 13 considering the whole study. The
      most abundant species were the rodents Nectomys squamipes (n = 133), Akodon
      cursor (n = 74), Oligoryzomys nigripes (n = 25) and the marsupials Didelphis
      aurita (n = 58) and Philander frenatus (n = 50). Seven other rodents were
      captured once: Necromys lasiurus, Akodon montensis, Sooretamys angouya, Oecomys
      catherine, Oxymycterus judex, Euryzygomatomys spinosus and Trinomys iheringi.
      There were higher peaks for diversity and species richness during the winter
      (dry) months, probably due to higher food availability. The marsupials had a
      seasonal reproduction with highest population sizes at the end of the rainy
      seasons. Nectomys squamipes reproduced mostly during rainy periods. Akodon cursor
      reproduced predominantly in the winter with the highest population peaks
      occurring during this season. The analysis of the population dynamics of the
      rodent species indicated that no species behaved as an agricultural pest,
      probably due to the heterogeneous landscape of high rotativity of vegetable
      cultivation. Rodent populations were more susceptible to the removal procedure
      than marsupial ones.

PMID- 17505768
TI  - First record of Necrobia rufipes (De Geer, 1775) (Coleoptera; Cleridae)
      associated with pet food in Brazil.

PMID- 17505769
TI  - Rapid identification of capybara (Hydrochaeris hydrochaeris) using allele
      specific PCR.

PMID- 17505770
TI  - Production of different types of mannosylerythritol lipids as biosurfactants by
      the newly isolated yeast strains belonging to the genus Pseudozyma.
AB  - Mannosylerythritol lipids (MEL), which are abundantly secreted by yeasts, are one
      of the most promising biosurfactants known. To obtain various types of MEL and to
      attain a broad range of applications for them, screening of novel producers was
      undertaken. Thirteen strains of yeasts were successfully isolated as potential
      MEL producers; they showed high production yields of MEL of around 20 g l(-1)
      from 40 g l(-1) of soybean oil. Based on the taxonomical study, all the strains
      were classified to be the genus Pseudozyma. It is interesting to note that they
      were categorized into three groups according to their production patterns of MEL.
      The first group, which included 11 strains taxonomically closely related to high
      level MEL producers such as Pseudozyma antarctica and Pseudozyma aphidis, mainly
      produced 4-O-[(4',6'-di-O-acetyl-2',3'-di-O-alkanoyl)-beta-D-mannopyranosyl]-meso
      erythritol (MEL-A) together with 4-O-[(6'-mono-O-acetyl-2',3'-di-O-alkanoyl)-beta
      D-mannopyranosyl]-meso-erythritol (MEL-B) and 4-O-[(4'-mono-O-acetyl-2',3'-di-O
      alkanoyl)-beta-D-mannopyranosyl]-meso-erythritol (MEL-C) as the minor components.
      The second group of one strain, which was related to Pseudozyma tsukubaensis,
      predominantly produced MEL-B. The third group of one strain, which was closely
      related to Pseudozyma hubeiensis, mainly produced MEL-C; this is the first
      observation of the efficient production of MEL-C from soybean oil. Moreover, the
      major fatty acids of the obtained MEL-C were C(6), C(12), and C(16) acids, and
      were considerably different from those of the other MEL hitherto reported. The
      biosynthetic manner for MEL is thus likely to significantly vary among the
      Pseudozyma strains; the newly isolated strains would enable us to attain a large
      scale production of MEL and to obtain various types of MEL with different
      hydrophobic structures.

PMID- 17505771
TI  - Improvement of tolerance to freeze-thaw stress of baker's yeast by cultivation
      with soy peptides.
AB  - The tolerance to freeze-thaw stress of yeast cells is critical for frozen-dough
      technology in the baking industry. In this study, we examined the effects of soy
      peptides on the freeze-thaw stress tolerance of yeast cells. We found that the
      cells cultured with soy peptides acquired improved tolerance to freeze-thaw
      stress and retained high leavening ability in dough after frozen storage for 7
      days. The final quality of bread regarding its volume and texture was also
      improved by using yeast cells cultured with soy peptides. These findings promote
      the utilization of soy peptides as ingredients of culture media to improve the
      quality of baker's yeast.

PMID- 17505772
TI  - The effect of LRP5 polymorphisms on bone mineral density is apparent in
      childhood.
AB  - Bone mass acquired during childhood is the primary determinant of adult bone
      mineral density (BMD) and osteoporosis risk. Bone accrual is subject to genetic
      influences. Activating and inactivating LRP5 gene mutations elicit extreme bone
      phenotypes, while more common LRP5 polymorphisms are associated with normal
      variation of BMD. Our aim was to test the hypothesis that LRP5 gene polymorphisms
      influence bone mass acquisition during childhood. The association between LRP5
      gene polymorphisms and bone size and mineralization was examined in 819 unrelated
      British Caucasian children (n = 429 boys) aged 9 years. Height, weight, pubertal
      status (where available), total-body and spinal bone area, bone mineral content
      (BMC), BMD, and area-adjusted BMC (aBMC) were assessed. Dual-energy X-ray
      absorptiometry (DXA)-gene associations were assessed by linear regression, with
      adjustment for age, gender, pubertal status, and body size parameters. There were
      140, 79, 12, and 2 girls who achieved Tanner stages I-IV, respectively, and 179
      and 32 boys who achieved Tanner stages I and II, respectively. The rs2,306,862
      (N740N) coding polymorphism in exon 10 of the LRP5 gene was associated with
      spinal BMD and aBMC (each P = 0.01) and total-body BMD and aBMC (P = 0.04 and
      0.03, respectively). Adjusting for pubertal stage strengthened associations
      between this polymorphism and spinal BMD and aBMC (P = 0.01 and 0.002,
      respectively). Individuals homozygous for the T allele had greater spinal BMD and
      aBMC scores than those homozygous for the C allele. A dose effect was apparent as
      the mean spinal BMD and aBMC of heterozygous TC individuals were intermediate
      between those of their TT and CC counterparts. The N740N polymorphism in exon 10
      of LRP5 was associated with spinal BMD and aBMC in pre- and early pubertal
      children. These results indicate that LRP5 influences volumetric bone density in
      childhood, possibly through effects on trabecular bone formation.

PMID- 17505774
TI  - Association between systemic calcified atherosclerosis and bone density.
AB  - Both atherosclerosis and osteoporosis are responsible for significant morbidity
      and mortality, are independent predictors of cardiovascular disease (CVD) events,
      and may share common regulatory mechanisms as well as histopathology. Multiple
      reports of weak or null relationships between traditional CVD risk factors and
      calcified atherosclerosis have heightened interest in novel predictors of
      arterial calcium. One such hypothesis is for an inverse relationship between bone
      mineral density (BMD) and calcified coronary atherosclerosis. Although contrary
      findings have been reported, the majority of cross-sectional and all prospective
      studies have demonstrated a significant inverse association between arterial
      calcium deposits and BMD. The few studies that include men are equivocal, and, to
      date, no study has investigated the relationship between BMD and systemic
      arterial calcium. The aim of this study was to test the hypothesis that lumbar
      BMD is significantly associated with the presence of arterial atherosclerotic
      calcium in the carotid, coronary, and iliac vascular beds as well as the aorta.

PMID- 17505773
TI  - Relationship of volumetric bone mineral density and structural parameters with
      ERalpha gene polymorphisms.
AB  - Bone mineral density (BMD) contributes to bone strength, and methods for clinical
      assessment of bone quality characteristics beyond what can be gathered by BMD are
      awaited. Peripheral quantitative computed tomography (pQCT) allows for separate
      assessments of cortical and trabecular bone, providing information on bone
      geometry. Previous studies examining the relationship between estrogen receptor
      alpha (ERalpha) gene polymorphisms and BMD have been performed in large
      populations. However, only limited information is available on the possible
      segregation of ERalpha gene polymorphisms with bone structural properties. The
      aim of our study was to evaluate the association of XbaI and PvuII ERalpha gene
      polymorphisms with QCT parameters. We studied 900 subjects (541 women, 449 men)
      participating to the InCHIANTI study. By tibial pQCT we evaluated trabecular
      volumetric BMD, cortical volumetric BMD, cortical bone area, and cortical
      thickness (CtTh). Subjects were genotyped for ERalpha gene PvuII and XbaI
      polymorphisms. Analysis of variance was used for statistical analysis. Male
      subjects with PP and XX genotypes had higher geometric parameters, and female
      subjects with XX and PP genotypes showed higher densitometric parameters than
      other genotypes; however, the differences did not reach statistical significance.
      After adjustment for potential confounders, we found a significant (P = 0.002)
      CtTh difference across PvuII polymorphism in male subjects, with higher CtTh
      values in PP genotypes with respect to Pp and pp genotypes. These results show a
      relationship between the presence of the P allele and higher values of CtTh in
      male subjects, indicating for ERalpha a role in the control of tibial bone
      geometry.

PMID- 17505775
TI  - Histologic study of coronary, radial, ulnar, epigastric and internal thoracic
      arteries: application to coronary artery bypass grafts.
AB  - The biometry and the histology of coronary, radial, ulnar, epigastric and
      internal thoracic arteries were studied in order to investigate the cause of
      their occlusions in coronary bypass grafts and to improve the results of these
      bypass grafts. These various arteries were removed from 40 anatomical specimens
      (27 males and 13 females). We found a correlation between the internal calibers
      of the ulnar and coronary arteries in males. Intimal changes and the presence of
      atheromatous plaque were observed in coronary, radial and ulnar arteries, but
      never in the internal thoracic artery. Like coronary arteries and their branches,
      radial, ulnar and epigastric arteries are muscular arteries and ageing results in
      thickening of the intima, which becomes fibrotic with migration of myocytes from
      the media and duplication of the internal elastic lamina. The media becomes
      fibrous, hypertrophic or atrophic. In contrast, the internal thoracic artery is
      an elastic artery, like the aorta. Ageing is characterized by loss, over a
      variable extent, of one or several elastic laminae of the media and more marked
      intimal thickening. Although anatomically, the caliber of radial, ulnar, and
      epigastric arteries remains adapted to that of coronary arteries, the long-term
      patency of radial, ulnar and epigastric arteries used as grafts is related to
      their histological characteristics.

PMID- 17505776
TI  - Anoxybacillus rupiensis sp. Nov., a novel thermophilic bacterium isolated from
      Rupi basin (Bulgaria).
AB  - Three strains of a novel thermophilic, strictly aerobic, Gram-positive, spore
      forming hemo-organotrophic bacterium were isolated from three hot springs in the
      region of Rupi basin, Bulgaria as producers of amylolytic enzymes. Their 16S rRNA
      gene sequences (first 500 nucleotides) were very similar (99.8%). Strains were
      able to ferment a wide spectrum of carbohydrates such as sugars, polyols, and
      polysaccharides like xylan, glycogen and starch. Optimal growth was observed at
      55-58 degrees C, and pH at 6.0-6.5. Phylogenetic analysis of the whole 16S rRNA
      gene sequence clustered the strain R270(T) with the representatives of the genus
      Anoxybacillus and with Geobacillus tepidamans. The G + C content of the genomic
      DNA was 41.7%. DNA-DNA hybridization analysis revealed low homology with the
      closest relatives (32.0 mol% homology to Geobacillus tepidamans). Fatty acid
      profile (major fatty acids iso-C15:0 and iso-C17:0) confirmed the affiliation of
      the strain to the genus Anoxybacillus. On the basis of the data presented here,
      we propose that strain R270(T), represents a new species of the genus
      Anoxybacillus for which, we recommend the name Anoxybacillus rupiensis sp. nov.
      (=DSM 17127(T) = NBIMCC 8387(T)). The 16S rRNA gene sequence data of a strain
      R270(T) have been deposited in the EMBL databases under the accession number
      AJ879076.

PMID- 17505777
TI  - Post-acute response of 9L gliosarcoma to Photofrin-mediated PDT in athymic nude
      mice.
AB  - The objective of this study is to measure the chronic responses of 9L glioma and
      normal brain to photodynamic therapy (PDT). Tumor size, proliferation activity of
      glioma cells, and vascular endothelial growth factor (VEGF) expression in both
      the tumor area and the brain adjacent to tumor (BAT) were observed 7 days after
      clinically relevant doses of PDT treatment. 9L Gliosarcoma cells were implanted
      into the brain of 20 athymic nude mice. Fifteen mice were injected
      intraperitoneally with Photofrin at a dose of 2 mg/kg on day 6 after tumor
      implantation and were treated with laser at different optical doses of 40 J/cm(2)
      (n = 5), 80 J/cm(2) (n = 5), and 120 J/cm(2) (n = 5) at 24 h after Photofrin
      injection, respectively. The remaining five tumor-bearing mice served as a tumor
      only control. All animals were killed 14 days after tumor implantation.
      Hematoxylin and eosin and immunostaining were performed to assess tumor volume,
      VEGF expression in the tumor and the BAT, as well as Ki67 expression in the tumor
      area. The tumor volume of the mice receiving 80 or 120 J/cm(2) group was
      significantly smaller than the control group (p < 0.01). VEGF immunoreactivity in
      the BAT was significantly increased in the 120 J/cm(2) PDT-treated mice (p <
      0.001), compared with the immunoreactivity seen in untreated mice and those
      receiving Photofrin and lower optical doses. No significant differences were
      detected in the proliferation of glioma cells and VEGF expression in the tumor
      area between these groups. These data indicate that PDT can shrink tumor,
      especially at the high light dose, and that PDT induces expression of VEGF in the
      BAT, which is associated with tumor recurrence. Therefore, PDT combined with anti
      angiogenic agents may be an effective treatment strategy for glioma.

PMID- 17505778
TI  - Unexpected case of aplastic anemia in a patient with glioblastoma multiforme
      treated with Temozolomide.
AB  - We report the case of a 30-year-old woman with glioblastoma multiforme (GBM)
      treated with surgery followed by concomitant Temozolomide (TMZ) and external beam
      radiation, which she tolerated well without any interruptions. However, when she
      was being evaluated for adjuvant Temozolomide, she developed progressive decline
      in leukocyte counts and platelet counts and subsequently, febrile neutropenia
      with bleeding manifestations. A bone marrow aspiration and biopsy done showed a
      gross hypocellular bone marrow with very few erythriod and myeloid cells and no
      suggestion of progenitor cells, consistent with aplastic anemia.

PMID- 17505780
TI  - Eye bank issues: II. Preservation techniques: warm versus cold storage.
AB  - Most of the tissue used for penetrating keratoplasty is issued through eye banks
      that store the corneoscleral button either in hypothermic storage at 2-6 degrees
      C or in organ culture at 31-37 degrees C. These two preservation techniques
      differ in technical aspects, tissue evaluation possibilities, storage time and
      microbiological safety. Hypothermic storage is simple and requires little
      expensive equipment. In general a pre-storage evaluation of the endothelium is
      performed by specular microscopy and storage time is usually around 7-10 days.
      Organ culture is a relatively complicated technique requiring more expertise and
      well-equipped facilities. Evaluation of the endothelium is not only performed
      before storage, but is routinely performed after storage through the use of light
      microscopy. With organ culture the allowed storage period is longer, up to four
      weeks. The vulnerability of organ culture to microbial contamination can be
      turned into an advantage because it allows the detection of residual micro
      organisms on the cornea before surgery. Both preservation techniques seem to
      result in similar graft survival. The method of choice for preservation of the
      donor cornea is dictated by a number of factors mentioned in this review and this
      helps to explain the geographical differences in the use of the different
      techniques.

PMID- 17505781
TI  - Hemodynamic response to intravitreal triamcinolone in eyes with macular edema:
      intravitreal triamcinolone and ocular blood flow.
AB  - PURPOSE: To assess ocular hemodynamic response to intravitreal triamcinolone in
      patients with macular edema due to diabetes or retinal vein occlusion. METHODS:
      Forty-three patients that were injected by intravitreal triamcinolone acetonide
      (0.1 cc 4 mg) for unilateral macular edema due to diabetes mellitus (n = 17) and
      occlusion of retinal vein (n = 26) underwent ocular hemodynamic evaluation by
      color Doppler imaging (CDI) before and one, two and three months after injection.
      Non-injected fellow eyes as well as 16 healthy volunteers were also evaluated.
      RESULTS: In patients with diabetic macular edema, there was no hemodynamic
      difference between eyes to be injected and non-injected at baseline (P > 0.23).
      Compared to controls, a significant difference existed in the ophthalmic artery
      resistant index (P = 0.001) and end-diastolic velocity (P < 0.001) in diabetics.
      At one month, compared to fellow eyes, change in end diastolic velocity from
      baseline in treated eyes was significantly decreased in posterior ciliary
      arteries (0.68 +/- 0.34 cm/s [mean +/- SEM] vs. -1.04 +/- 0.81 cm/s, P = 0.012).
      Throughout the study period, no significant alteration from baseline in the
      resistant index of any artery was noted in treated diabetic eyes (P > 0.05). In
      eyes with retinal vein occlusion, baseline CDI evaluation demonstrated reduced
      posterior ciliary arteries systolic flow velocity compared to fellow and control
      eyes (13.24 +/- 1.04 cm/s, 16.37 +/- 0.76 cm/s and 14.33 +/- 1.41 cm/s,
      respectively, P = 0.007). Increased peak systolic velocity in the posterior
      ciliary arteries at one week (P = 0.02), one month (P = 0.005) and two months (P
      = 0.04), and increase in central retinal artery resistant index at one month was
      noted (P = 0.05). CONCLUSION: Intravitreal triamcinolone temporarily changed
      central retinal artery blood flow and posterior ciliary arteries' peak systolic
      blood velocity in eyes with retinal vein occlusion whilst no response of blood
      flow to triamcinolone injection but only transiently altered end diastolic blood
      velocity in posterior ciliary arteries was observed in diabetic eyes.

PMID- 17505782
TI  - Characterization of PHB storage in activated sludge extended filamentous bacteria
      by automated colour image analysis.
AB  - The storage of poly-beta-hydroxybutyrate (PHB) in extended filamentous bacteria
      from activated sludge was monitored by Sudan Black staining: PHB granules were
      blue in the reddish filaments counterstained by safranin. By quantitative image
      analysis of colour images grabbed on an optical microscope, the distribution of
      the PHB loading of the extended filaments was estimated by determination of the
      proportion of blue pixels of their skeleton. The method was applied for different
      feed compositions to demonstrate its ability to monitor the PHB synthesis and
      storage capacity of filamentous bacteria in mixed cultures. Fast PHB storage,
      within a few hours, could be observed with acetate-based feeding solutions but
      the storage rate decreased with more complex feeds (meat extract based feed,
      wastewater).

PMID- 17505783
TI  - Efficient one-step starch utilization by industrial strains of Saccharomyces
      cerevisiae expressing the glucoamylase and alpha-amylase genes from Debaryomyces
      occidentalis.
AB  - Amylolytic industrial polyploid strains of Saccharomyces cerevisiae (ATCC 4126,
      ATCC 9763 and ATCC 24858) expressing a glucoamylase gene (GAM1) or an alpha
      amylase gene (AMY) from Debaryomyces occidentalis were developed. The
      glucoamylase activity of S. cerevisiae ATCC 9763 expressing the GAM1 gene was 3.7
      times higher than that of D. occidentalis. On the other hand, alpha-amylase
      activity in the corresponding strain expressing the D. occidentalis AMY gene
      increased 10-times relative to D. occidentalis. These two recombinant yeast
      strains expressing the GAM1 gene and AMY gene, respectively were cultured
      simultaneously to produce both glucoamylase and alpha-amylase for efficient one
      step utilization of starch. Growth, substrate utilization and enzyme activity of
      these strains are described.

PMID- 17505784
TI  - Production of Fusarium solani f. sp. pisi cutinase in Fusarium venenatum A3/5.
AB  - Fusarium venenatum A3/5 was transformed using the Aspergillus niger expression
      plasmid, pIGF, in which the coding sequence for the F. solani f. sp. pisi
      cutinase gene had been inserted in frame, with a KEX2 cleavage site, with the
      truncated A. niger glucoamylase gene under control of the A. niger glucoamylase
      promoter. The transformant produced up to 21 U cutinase l(-1) in minimal medium
      containing glucose or starch as the primary carbon source. Glucoamylase (165 U l(
      1) or 8 mg l(-1)) was also produced. Both the transformant and the parent strain
      produced cutinase in medium containing cutin.

PMID- 17505785
TI  - Long-term aerobic exercise protects the heart against ischemia/reperfusion injury
      via PI3 kinase-dependent and Akt-mediated mechanism.
AB  - OBJECTIVE: Physical activity has been shown to improve cardiovascular function
      and to be beneficial to type 2 diabetic patients. However, the effects of aerobic
      exercise (AE) on myocardial ischemia/reperfusion (MI/R) are largely unclear.
      Therefore, the aims of the present study were to determine whether long-term AE
      can protect the heart against I/R injury, and if so, to investigate the
      underlying mechanism. METHODS: Adult male Sprague-Dawley rats were randomly
      subjected to 8 weeks of either sedentary or free-loading swimming exercise (3
      h/day, 5 d/week). Then the animals were subjected to 30 min MI followed by 4 h R.
      Arterial blood pressure and left ventricular pressure (LVP) were monitored
      throughout the whole MI/R procedure. Plasma creatine kinase (CK) and lactate
      dehydrogenase (LDH) activities were measured spectrophotometrically. Myocardial
      infarction and myocardial apoptosis (TUNEL analysis) were determined in a blinded
      manner. RESULTS: MI/R caused significant cardiac dysfunction and myocardial
      apoptosis (strong TUNEL-positive staining). Compared with sedentary group, rats
      subjected to 8 weeks of AE showed protection against MI/R as evidenced by reduced
      myocardial infarction (26.8 +/- 1.5% vs. 35.3 +/- 2.4%, n = 8, P < 0.05),
      inhibited cardiomyocyte apoptosis (decreased apoptotic index (12.4 +/- 1.1% vs.
      21.0 +/- 1.7%, n = 8, P < 0.01) and decreased myocardial caspase-3 activity),
      decreased plasma CK and LDH activities and improved recovery of cardiac
      systolic/diastolic function (including LVSP and +/-LVdP/dt) at the end of R.
      Moreover, exercise resulted in 1.7-fold, 2.5-fold and 2.5-fold increases in Akt
      expression, Akt phosphorylation and glycogen synthase kinase-3beta
      phosphorylation in I/R myocardium, respectively (n = 3, all P < 0.05). More
      importantly, treatment with wortmannin, a PI3 kinase inhibitor, 15 min before R
      not only significantly blocked Akt phosphorylation (P < 0.05) in exercise rats,
      but also abolished long-term AE-induced cardioprotection for the I/R heart as
      manifested by increased apoptosis and myocardial infarction, and reduced cardiac
      function. CONCLUSION: Long-term AE exerts cardioprotective effect against MI/R
      injury, including anti-cardiomyocyte apoptosis, which is at least partly via PI3
      kinase-dependent and Akt-mediated mechanism.

PMID- 17505786
TI  - Apoptosis by cisplatin requires p53 mediated p38alpha MAPK activation through ROS
      generation.
AB  - Cisplatin is one of the major chemotherapeutic weapons used against different
      human cancers, although its mechanism to induce apoptosis is not fully
      understood. The presence of wild type p53 has been suggested to be important for
      cisplatin cytotoxicity, hence we found that cisplatin induced apoptosis in cell
      lines with functional p53. Using the HCT116 colon carcinoma derived cell line we
      have established that the apoptotic activity of cisplatin requires the onset of a
      p53-mediated p38alpha MAPK pathway through generation of reactive oxygen species
      (ROS). HCT116 p53-deficient cells were much less sensitive to apoptosis by
      cisplatin than their p53wt counterparts, where apoptosis was strongly inhibited
      by antioxidants. Moreover, the presence of pifithrin-alpha, an inhibitor of p53
      transcriptional activity, blocked cisplatin-induced apoptosis, reduced the
      generation of ROS produced upon cisplatin treatment. In addition, we have
      identified p38alpha as the isoform necessary for cisplatin-induced apoptosis,
      upon activation by p53-mediated ROS production. p38alpha MAPK contributes to
      further activation of p53, which leads to a positive feedback loop, p38alpha
      MAPK/p53. We conclude that the p53/ROS/p38alpha MAPK cascade is essential for
      cisplatin-induced cell death in HCT116 cells and the subsequent p38alpha/p53
      positive feedback loop strongly enhances the initial p53 activation.

PMID- 17505788
TI  - [Abstracts from the 13th DEGRO Annual Meeting, the 11th SASRO Annual Meeting and
      the 23rd OGRO Annual Meeting, 2006 and 2007].

PMID- 17505790
TI  - A maternal methyl-containing diet alters learning ability in the Morris swimming
      test in adult rats.
AB  - Maternal choline diet is known to affect the processes of spatial learning. We
      report here our studies of learning ability in the Morris swimming test in the
      adult offspring of maternal rats given a methyl-containing supplement enriched
      with choline and betaine during pregnancy and lactation. Increases in the time
      taken to find the invisible platform and the duration of swimming close to the
      vessel walls were seen, these demonstrating worsening of learning ability in
      response to the maternal diet. Changes in the platform search strategy were not
      associated with increases in anxiety in male rats. The possible role of a
      maternal methyl-containing diet in altering the expression of genes controlling
      the development of the nervous system is discussed.

PMID- 17505791
TI  - Gender differences in interhemisphere interactions during distributed and
      directed attention.
AB  - The role of gender in the functional organization of the hemispheres was studied
      in relation to the conditions of focusing of attention during the memorization of
      competitively presented verbal information. Analysis of the reactivity of the
      coherence of cortical biopotentials in six frequency ranges (4-30 Hz) showed that
      voluntary selection of information from one auditory channel, as compared with
      the situation in which attention was distributed between both ears, was
      accompanied by an increase in the anterofrontal interaction in men and in the
      parietal-occipital areas of the cortex in the theta1 range in women. In the beta1
      range, focusing of attention to the right or left ear during memorizing of words
      was associated with a contralateral increase in intrahemisphere coherence in men,
      while there were no significant changes in coherence in women. Changes in
      coherence in the theta1 and beta1 rhythms, depending on the conditions of
      distribution of attention and the nature of correlational connections between the
      reproduction of words and the patterns of reactivity of coherence in these
      frequency ranges, suggest that word remembering in men is associated mainly with
      a dominance of regulatory influences from the anterior attention system, while in
      women it was associated mainly with the posterior system.

PMID- 17505792
TI  - Effects of impaired testosterone metabolism during prenatal ontogenesis on the
      level of anxiety and behavior of rats in a novel environment.
AB  - The effects of administration of the aromatase inhibitor 1,4,6-androstatrien-3.17
      dione (ATD) to female rats during the last third of pregnancy on the formation of
      behavior of offspring of both genders in a novel environment were studied. Animal
      behavior was assessed in the open field and elevated cross maze tests. Inhibition
      of testosterone aromatization during the prenatal period of development resulted
      in increases in anxiety and emotionality in experimental rats at age one month;
      increases in these measures in adult animals were seen in both males and females
      exposed to prenatal ATD. Intergender differences between control males and
      experimental females, in terms of behavioral measures in the novel environment
      such as motor activity, the duration of the freezing and grooming reactions, as
      well as well the level of anxiety, disappeared. It is concluded that impairment
      of testosterone metabolism during the prenatal period of development affects the
      formation of the behavior of rats in a novel environment as determined by genetic
      gender.

PMID- 17505793
TI  - Effects of protein synthesis inhibitors on the sensitization of a defensive
      response in common snails and potentiation of the cholinosensitivity of command
      neurons.
AB  - The effects of protein synthesis inhibitors on short-term sensitization of a
      defensive reaction in common snails and the potentiation of the
      cholinosensitivity of command neurons were studied. The protein synthesis
      inhibitor anisomycin did not prevent behavioral sensitization. Anisomycin and the
      irreversible protein synthesis inhibitor saporin changed the dynamics of
      potentiation of command neuron cholinosensitivity. We suggest that the
      sensitization of the defensive response of the common snail studied here does not
      require the synthesis of new proteins.

PMID- 17505794
TI  - Changes in spontaneous brain bioelectrical activity during transcranial
      electrical and electromagnetic stimulation.
AB  - The systems responses of the brain to therapeutic transcranial electrical and
      electromagnetic stimulation were studied and the neurophysiological criteria for
      assessing the efficacy of this treatment were identified using comparative
      clinical and experimental studies with analysis of spontaneous bioelectrical
      activity, along with assessment of behavioral and clinical measures. Study groups
      consisted of six patients with chronic post-traumatic unconscious states during
      courses of transcranial electrical stimulation and 17 intact Wistar rats
      subjected to transcranial electromagnetic stimulation. A relationship was found
      between the effects of transcranial stimulation and the initial level of
      intercenter interactions of brain bioelectrical activity assessed in terms of
      coherence. Hypersynchronization of biopotentials, identified as a major element
      in the reactivity to this type of stimulation, may be of the greatest value in
      the recovery of patients with cerebral pathology in cases with initially reduced
      levels of intercenter interactions in the absence of pathologically increased
      functional connections in the brain.

PMID- 17505795
TI  - Influences of an acoustic signal with ultrasound components on the acquisition of
      a defensive conditioned reflex in Wistar rats.
AB  - The effects of short (90 sec) exposures to a complex acoustic signal with
      ultrasound components on the acquisition of a defensive conditioned two-way
      avoidance reflex using an electric shock as the unconditioned stimulus in a
      shuttle box were studied in female Wistar rats. This stimulus induced audiogenic
      convulsions of different severities in 59% of the animals. A scale for assessing
      the ability of rats to acquire the conditioned two-way avoidance reflex was
      developed. Presentation of the complex acoustic signal was found to be a powerful
      stressor for Wistar rats, preventing the acquisition of the reflex in the early
      stages (four and six days) after presentation. This effect was independent of the
      presence and severity of audiogenic convulsions in the rats during presentation
      of the acoustic signal. On repeat training nine days after the acoustic signal
      (with the first session after four days), acquisition of the reflex was hindered
      (as compared with controls not presented with the acoustic signal). However, on
      repeat training at later time points (1.5 months after the complex acoustic
      signal, with the first session after six days), the rats rapidly achieved the
      learning criterion (10 correct avoidance responses in a row). On the other hand,
      if the acoustic signal was presented at different times (immediately or at three
      or 45 days) after the first training session, the animals' ability to acquire the
      reflex on repeat training was not impaired at either the early or late periods
      after exposure to the stressor. These results suggest that the complex acoustic
      signal impairs short-term memory (the process of acquisition of the conditioned
      two-way avoidance reflex at the early post-presentation time point) but has no
      effect on long-term memory or consolidation of the memory trace.

PMID- 17505796
TI  - Protective effects of interleukin-10 on the development of epileptiform activity
      evoked by transient episodes of hypoxia in rat hippocampal slices.
AB  - The aim of the present work was to study the effects of interleukin-10 at
      concentrations of 1 and 10 ng/ml on the development of epileptiform discharges
      evoked in pyramidal neurons in field CA3 in rat hippocampal slices by transient
      episodes of hypoxia. Three 3-min episodes of hypoxia led to decreases in the
      generation threshold for evoked trains of population spikes and an increase in
      the number of population spikes per train in pyramidal neurons of field CA1.
      Interleukin-10 at a concentration of 1 ng/ml completely eliminated the
      development of epileptiform activity, while its protective effect was less marked
      at a concentration of 10 ng/ml. These effects of interleukin-10 on living
      hippocampal slices in in vitro conditions show that they may be associated with
      the functions of this cytokine as an intercellular mediator of the central
      nervous system itself rather than being mediated by the peripheral immune system.
      The results of these studies provide the first experimental evidence of the
      action of the anti-inflammatory cytokine interleukin-10 on the development of
      hypoxia-evoked epileptiform events in the hippocampus.

PMID- 17505797
TI  - Effects of BT-melanin on recovery of operant conditioned reflexes in rats after
      ablation of the sensorimotor cortex.
AB  - An increase in corticofugal plasticity was demonstrated in adult rats after
      unilateral ablation of the sensorimotor cortex accompanied by intramuscular
      administration of low concentrations of BT-melanin solution. The result was
      acceleration of the process of compensatory recovery in the central nervous
      system, this being supported by the rapid recovery of a previously acquired
      operant conditioned reflex and movement of the paralyzed limb as compared with
      control animals. It is suggested that compensation of the motor deficit arising
      after ablation of the sensorimotor cortex is mediated by the ability of the two
      major motor systems of the brain - the corticospinal and the corticorubrospinal -
      to exhibit mutual substitution of their functions. This phenomenon of the
      functional switching of descending influences also occurred in rats of the
      control group not exposed to BT-melanin. However, the difference between the
      recovery times of the operant conditioned reflex and limb movement in the control
      and experimental groups provided evidence of an apparent acceleration in these
      processes as a result of BT-melanin. These results suggest that low
      concentrations of BT-melanin may have applied uses.

PMID- 17505799
TI  - Local changes in the redox potential in the rabbit cerebral cortex accompanying
      the acquisition of a conditioned defensive reflex.
AB  - The oxidative-reductive (redox) potential (E) of brain tissue depends on the
      ratio of the speeds of processes occurring in the glycolysis (the evolutionarily
      ancient energy compartment operating without oxygen) and oxidative metabolism
      (evolutionarily younger and energetically more efficient) compartments. E in the
      cortex was recorded using implanted platinum electrodes. A conditioned defensive
      reflex (CDR) was developed by combination of a light and electrocutaneous
      stimulation (ECS) of the ear. The results showed that after a series of
      combinations of the light and the ECS, the light started to elicit a change in E.
      By 200 combinations, the brain developed both increases and decreases in E during
      combinations. As the number of combinations increased, increases in E were
      gradually replaced by decreases. We believe that this dynamic of the balance of
      the major sources of brain energy supply suggests that formation of the CDR may
      involve a significant role for subcellular structures receiving energy from
      oxidative metabolism formed at the relatively young evolutionary level, while the
      major source of energy for brain function during performance of the acquired CDR
      is the older evolutionary compartment - glycolysis.

PMID- 17505798
TI  - What are the mechanisms underlying the involvement of different subtypes of NMDA
      receptors in inducing long-term potentiation and depression in the hippocampus?
AB  - It has been hypothesized that the sign (direction) of modification of the
      efficiency of synaptic transmission depends on the subtype of N-methyl-D
      aspartate (NMDA)-sensitive receptors involved. Activation of NMDA receptors with
      2A subunits facilitates the induction of long-term potentiation, while receptors
      with 2B subunits facilitate the induction of long-term depression. However,
      experimental data have been obtained which contradict this hypothesis. We suggest
      an alternative hypothesis to explain currently available data. According to this
      hypothesis, activation of NMDA receptors containing different subunits can lead
      both to long-term potentiation and long-term depression, depending on the post
      tetanic increase in the postsynaptic Ca(2+) concentration relative to the
      increase induced by preceding stimulation. Activation of NMDA receptors
      containing 2B subunits can lead to long-term depression of the excitatory input
      to pyramidal neurons because of the presence of these receptors on inhibitory
      interneurons, with induction of long-term potentiation on the interneuron and
      potentiation of inhibitory transmission between interneurons and pyramidal cells.

PMID- 17505800
TI  - Resistance of the myocardium to ischemia and the efficacy of ischemic
      preconditioning in experimental diabetes mellitus.
AB  - Data on the influences of diabetes mellitus on the severity of ischemic damage to
      the myocardium are contradictory. We report here experiments using a model based
      on in vivo myocardial infarcts resulting from coronary occlusion to study the
      resistance of the myocardium in rats with alloxan-induced insulin-dependent
      diabetes mellitus to prolonged ischemia, along with studies of the infarct
      limiting efficacy of ischemic preconditioning. The results showed that after
      diabetes mellitus for six weeks, the relative size of infarcts was significantly
      less than in controls (39.8 +/- 8.8 and 62.3 +/- 6.6% of the size of the
      anatomical risk zone respectively, p < 0.01). In addition, animals with diabetes
      mellitus developed ischemic ventricular tachyarrhythmia significantly less often
      than controls. A single episode of ischemic preconditioning in animals with
      diabetes mellitus had a less marked infarct-limiting effect than the same
      procedure in controls. Thus, these data support the existence of an endogenous
      cardioprotective phenotype (metabolic preconditioning) in experimental diabetes.
      On the other hand, the efficacy of ischemic preconditioning was sharply decreased
      in diabetes.

PMID- 17505801
TI  - Local blood flow in the dorsal hippocampus and cerebellar cortex in the offspring
      of iodine-deficient rats.
AB  - Experimental studies demonstrated that hypothyroidism can lead to depressive
      behavior and that thyroid hormones can have antidepressant effects. Postnatal
      changes in local blood flow in the dorsal hippocampus and cerebellar cortex were
      studied in the offspring of rats kept in conditions of iodine deficiency at
      conception and throughout gestation. The data obtained from these studies showed
      that severe limitation of iodine intake before and during gestation leads to
      marked deficiency in the blood supply to both of these brain structures, though
      the decrease in local blood flow in the dorsal hippocampus was more marked.
      Addition of iodine to the diet of females prevented this deficit of blood flow in
      both structures.

PMID- 17505802
TI  - The psychomodulatory action of subpyrogenic doses of interleukin-1beta in
      conditions of chronic administration to rats.
AB  - The effects of interleukin-1beta at low, subpyrogenic doses on behavior were
      studied in rats. Signs of increased anxiety were evident by day 5 of treatment
      courses. These results provide evidence supporting the role of proinflammatory
      cytokines in the pathogenesis of emotional disorders.

PMID- 17505803
TI  - Rhythmic electrical activity in branches of the stellate ganglion in the cat
      during postnatal ontogenesis.
AB  - Electrical activity in branches of the stellate ganglion was studied in neonatal
      cats and cats aged 10, 20, and 30 days and two and six months, with subsequent
      spectral analysis. Maturation of the pattern of the baseline rhythmic activity in
      branches of the ganglion differed during ontogenesis in the kittens. The neonatal
      period until the end of the second month of life was accompanied by an increase
      in the amplitude of electrical oscillations. Synchronous discharges in
      postganglionic fibers consisted of slow, low-amplitude oscillations at the
      respiratory frequency and heart rate in neonatal and 10-day-old-kittens.
      Synchronous spike activity with a frequency of about 10 Hz appeared from day 20
      of life. The formation of the pattern of sympathetic nerve fiber discharges was
      complete by the second month of life.

PMID- 17505804
TI  - Effects of activation and blockade of NMDA receptors on the extinction of a
      conditioned passive avoidance response in mice with different levels of anxiety.
AB  - The effects of an agonist (D-cycloserine) and an antagonist (dizocilpine) of N
      methyl-D-aspartate (NMDA) receptors on the learning and extinction of a
      conditioned passive avoidance response were studied in mice with low,
      intermediate, and high levels of anxiety. In intermediate-anxiety mice, D
      cycloserine (30 mg/kg) had no effect on learning but accelerated extinction,
      while dizocilpine (0.15 mg/kg) degraded acquisition of the reflex but delayed
      extinction. In high-anxiety mice, with good learning and no extinction, D
      cycloserine had no effect, while dizocilpine decreased learning and facilitated
      retention of performance of the memory trace at the ongoing level in conditions
      promoting extinction. In low-anxiety mice, D-cycloserine degraded learning and
      accelerated extinction, while dizocilpine completely blocked learning and the
      retention of the passive avoidance response.

PMID- 17505805
TI  - Structural asymmetry of the basal nucleus of Meynert in men and women.
AB  - The structure of Meynert's nucleus was studied using quantitative
      neurohistological measures in 11 cases from the collection of the Institute of
      the Brain, Russian Academy of Medical Sciences. The set consisted of seven men
      and four women aged 19-60 years (apart from one aged 70 years) and were patients
      who had died suddenly with no history of neurological or mental diseases. The
      following parameters were measured: neuron field profile, neuron density, total
      and satellite glial density, and the proportion of glia consisting of satellite
      glia and the proportion of neurons surrounded by satellites. All individual
      measures were analyzed statistically and differences between the hemispheres were
      determined. On a background of a large spread in individual values, there was
      significant asymmetry in neuron field profile area in different directions in men
      and women and tendencies to a greater neuron density on the left and a greater
      glial cell density on the right. Measures of satellite glia showed particularly
      large variation, with the result that the only identifiable result was a greater
      proportion of satellite-surrounded neurons in the right hemisphere. Overall,
      there was a tendency to somewhat greater asymmetry in the structure of this
      nucleus in men.

PMID- 17505806
TI  - Efficacy of neuroprotectors in patients with tension headaches.
AB  - Studies were performed on 126 patients with chronic tension headache (CTH).
      Patients were divided into two groups - an experimental group (64 patients) and a
      control group (62). Control patients received standard treatment (tizanidine,
      fluoxetine, vinpocetin, and manual acupressure of active points in the trapezius
      muscles and the temporomastoid area of the head); the experimental group also
      received Mexidol. Clinical and neurophysiological studies, including
      electromyography, were performed before and after treatment. Comparison of the
      treatment outcomes in the two groups showed that inclusion of Mexidol into the
      complex therapy of chronic CTH led to faster and more marked clinical effects.

PMID- 17505807
TI  - Signs of apoptosis of immunocompetent cells in patients with depression.
AB  - A total of 26 patients with depression and 20 healthy subjects were studied.
      Measures of apoptosis of peripheral blood lymphocytes and serum cortisol
      concentrations were determined. A significant increase in lymphocyte apoptosis
      was found in patients with depression, resulting in an increase in the proportion
      of lymphocytes expressing the FAS receptor; cells with morphological signs
      characteristic of apoptosis (nuclear condensation, vacuolization) were also seen.
      Changes in cellular immunity were observed on the background of clinical
      depressive symptomatology, with decreases in the total numbers of T-lymphocytes
      (CD3(+)), T-helpers (CD4(+)), and natural killer cells (CD16(+)) as compared with
      numbers in healthy subjects. Serum cortisol levels were elevated. Correlation
      analysis revealed an interaction between high cortisol levels and decreases in T
      helper cells (CD4(+)) and increases in apoptosis receptor expression in patients
      with depressive disorder.

PMID- 17505808
TI  - Effects of the gender factor and neonatal androgenization on the
      dendroarchitectonics of neurons in the dorsomedial nucleus of the amygdaloid body
      of the brain.
AB  - The aim of the present work was to identify gender-related differences in the
      dendroarchitectonics of neurons in the dorsomedial nucleus of the amygdaloid body
      and the role of androgens in their formation during period of sexual
      differentiation of the brain in rats. Studies using the Golgi method showed that
      the quantitative characteristics of long-axon sparsely branched neurons of all
      classes - neuroblast-like, short-dendrite, and reticular - reflected the
      influences of gender. In particular, long-axon sparsely branched neurons were
      found to have more abundant branching primary dendrites and greater total
      dendrite lengths in adult males than in females. Adult females subjected to
      neonatal androgenization by administration of testosterone propionate at a dose
      of 1250 microg showed different neuron characteristics five days after birth as
      compared with normal females, and these were more marked than in males.

PMID- 17505809
TI  - A periodic pattern in the distribution of cytochrome oxidase activity in the
      visual cortex in kittens.
AB  - The aim of the present work was to study the distribution of cytochrome oxidase
      activity in the visual cortex of kittens in normal conditions. Studies were
      performed using computer filtration of digitized images of frontal sections. The
      occurrence of regularly alternating levels of enzyme activity was demonstrated in
      layers III, IV, and VI of field 17 and layers IV and VI in field 18.

PMID- 17505810
TI  - [Pitfalls in magnetic resonance imaging. What should the anaesthesiologist
      know?].
AB  - The constantly extending indication spectrum of magnetic resonance imaging (MRI)
      is a challenge for the anaesthesiologist, who is being increasingly more
      consulted for assistance during the examination. Due to the special technology of
      MRI the anaesthetic technique differs substantially from that in the operating
      theatre. In addition to the permanent strong magnetic field the intermittently
      used high frequency impulses are also a potential danger for the patient.
      Patients with metal implants (e.g. cardiac pacemaker) are particularly at risk.
      For the safe treatment of patients during MRI a special MRI compatible
      anaesthesia equipment is necessary. Unsuitable devices can lead to malfunctioning
      or to projectile effects (attracting ferromagnetic objects into the magnet)
      causing injury to the patients. This paper describes the MRI technology and the
      associated dangers for the patient as well as the characteristics of the
      anaesthetic techniques.

PMID- 17505811
TI  - [Inhalation anaesthesia: it remains exciting!].

PMID- 17505812
TI  - MMP2 role in breast cancer brain metastasis development and its regulation by
      TIMP2 and ERK1/2.
AB  - Matrix metalloproteinase 2 (MMP2) is important in breast cancer (BC) invasion and
      metastasis. We previously reported that BC brain metastases, in a rat syngeneic
      model developed in our laboratory, have high expression and activity of MMP2. The
      MMP2 mechanism of action in the brain is still under intense scrutiny. To study
      the role of MMP2 in the development of BC brain metastasis we transfected ENU1564
      rat mammary adenocarcinoma cells with tissue inhibitor of MMP2 (TIMP2). Animals
      inoculated with ENU1564-TIMP2 cells had decreased orthotopic tumor growth,
      decreased orthotopic metastatic behavior and did not develop brain metastases.
      These results were associated with decreased MMP2 activity, demonstrated by gel
      zymography. Mitogen activated protein kinase (MAPK) pathway components, such as
      ERK1/2, have been correlated to MMP expression and/or astrocyte activity. We
      found that BC brain metastases have peripheral astrocyte reactivity and higher
      expression of glial fibrillary acidic protein (GFAP) and phosphorylated-ERK1/2 (p
      ERK1/2). Additionally, rat astrocyte-conditioned media increased in vitro
      invasion of ENU1564 cancer cells and increased expression of MMP2 and p-ERK1/2.
      Blockage of ERK1/2 phosphorylation by treatment with MEK inhibitor (PD98059)
      decreased the expression of MMP2 in cancer cells grown in rat astrocyte
      conditioned media. Our results are highly suggestive that MMP2 plays a role in
      the development of BC metastases, in particular to the brain. Furthermore, our
      results suggest that astrocyte factors and the ERK1/2 signaling pathway may be
      associated with BC brain metastasis development; and that ERK1/2 may regulate
      MMP2 in a way that is modifiable by astrocyte factors.

PMID- 17505813
TI  - [Near-total ear amputation: anatomical bases and management].
AB  - BACKGROUND: In cases of near-total ear avulsions, replantation is often
      successful without microsurgery. The purpose of our study was to investigate the
      relevant vascular anatomy associated for ear survival. PATIENTS AND METHODS: Four
      cases of successful surgical intervention in near-total ear avulsions are
      presented. Injection studies using latex were performed to identify the blood
      supply to the auricle on 13 cadaveric ears. RESULTS: A small superior branch of
      the superficial temporal artery above the tragus was identified extending along
      the upper border of the auricle and connecting with the helical arcade. Below the
      tragus, a second small horizontal branch of the superficial temporal artery was
      identified. CONCLUSION: The auricle can survive near-total amputation based on a
      skin bridge above or below the tragus. One of the auricular branches of the
      superficial temporal artery seems sufficient for the blood supply to the ear and
      allows for a successful non-microsurgical operative repair.

PMID- 17505814
TI  - [Functional imaging for brain tumors (perfusion, DTI and MR spectroscopy)].
AB  - This contribution considers the possibilities involved with using functional
      methods in magnetic resonance imaging (MRI) diagnostics for brain tumors. Of the
      functional methods available, we discuss perfusion MRI (PWI), diffusion MRI (DWI
      and DTI) and MR spectroscopy (H-MRS). In cases of brain tumor, PWI aids in
      grading and better differentiation in diagnostics as well as for pre-therapeutic
      planning. In addition, the course of treatment, both after chemo- as well as
      radiotherapy in combination with surgical treatment, can be optimized. PWI allows
      better estimates of biological activity and aggressiveness in low grade brain
      tumors, and in the case of WHO grade II astrocytoma showing anaplasically
      transformed tumor areas, allows more rapid visu-alization and a better prediction
      of the course of the disease than conventional MRI diagnostics. Diffusion MRI,
      due to the directional dependence of the diffusion, can illustrate the course and
      direction of the nerve fibers, as well as reconstructing the nerve tracts in the
      cerebrum, pons and cerebellum 3-dimensionally. Diffusion imaging can be used for
      describing brain tumors, for evaluating contralateral involvement and the course
      of the nerve fibers near the tumor. Due to its operator dependence, DTI based
      fiber tracking for defining risk structures is controversial. DWI can also not
      differentiate accurately between cystic and necrotic brain tumors, or between
      metastases and brain abscesses. H-MRS provides information on cell membrane
      metabolism, neuronal integrity and the function of neuronal structures, energy
      metabolism and the formation of tumors and brain tissue necroses. Diagnostic
      problems such as the differentiation between neoplastic and non-neoplastic
      lesions, grading cerebral glioma and distinguishing between primary brain tumors
      and metastases can be resolved. An additional contribution will discuss the
      control of the course of glial tumors after radiotherapy.

PMID- 17505815
TI  - [Wilms' tumor in adults].
AB  - BACKGROUND: Wilms' tumor (nephroblastoma) is the most frequent renal tumor in
      childhood. In contrast nephroblastoma in adults is rare, and the disease used to
      have a poor prognosis. PATIENTS AND METHODS: Of 1,300 registered patients, a
      total of 41 patients older than 16 years were enrolled in the pediatric
      nephroblastoma trial from 1994 to 2005. Median age at diagnosis was 25.4 years
      (range: 16-62 years). Treatment was given according to the pediatric protocol.
      RESULTS: The adults had higher local stages, more frequent metastasis, and
      developed more toxicity due to therapy. Vincristine caused severe neurotoxicity
      in many cases. The distribution of histological subtypes was similar to the
      children's. The outcome is better than previously described with an overall
      survival of 71%. Patients with local stage I and II have an event-free survival
      of 84%. This is comparable to children's survival rates. CONCLUSION: Adults with
      nephroblastoma have a very good prognosis if treated according to a pediatric
      protocol.

PMID- 17505816
TI  - Lean rats with hypothalamic pro-opiomelanocortin overexpression exhibit greater
      diet-induced obesity and impaired central melanocortin responsiveness.
AB  - AIMS/HYPOTHESIS: Central pro-opiomelanocortin (Pomc) gene therapy ameliorates
      genetic- or age-related obesity. We hypothesised that this treatment would delay
      or prevent dietary obesity in young, lean rats. MATERIALS AND METHODS:
      Recombinant adeno-associated virus encoding Pomc (rAAV-Pomc) was delivered
      bilaterally into the basomedial hypothalamus of lean rats for 42 days. Food
      intake, body weight, serum hormones, brown adipose tissue (BAT) uncoupling
      protein 1 (UCP1) and mRNA levels of hypothalamic neuropeptides and melanocortin
      receptors were assessed. Beginning on day 43, half of the rats remained on chow
      while the others received a high-fat diet for 89 days. We examined energy balance
      and responsiveness to the melanocortin agonist melanotan II (MTII) or the
      antagonist SHU9119. RESULTS: Pomc gene delivery produced elevated hypothalamic
      Pomc mRNA (fourfold) and alpha-melanocyte-stimulating hormone levels in the
      arcuate nucleus (twofold). Food intake and body weight were not altered by rAAV
      Pomc in rats fed standard-chow. In rAAV-Pomc rats at day 42, perirenal fat and
      serum leptin decreased but overall visceral adiposity did not; expression of the
      hypothalamic agouti-related protein (Agrp) mRNA was elevated, whereas expression
      of melanocortin 3 and 4 receptor mRNA was reduced; BAT UCP1 protein increased
      nearly fourfold. The rAAV-Pomc rats fed the high-fat diet consumed more energy
      and gained more body weight compared with chow- or high-fat-fed controls that did
      not receive Pomc gene delivery. The anorexic response to MTII was impaired,
      whereas the orexigenic effect of SHU9119 was enhanced by rAAV-Pomc pretreatment.
      CONCLUSIONS/INTERPRETATION: Delivery of the Pomc gene alters energy homeostasis
      in lean rats, predisposing them to diet-induced obesity. Diminished hypothalamic
      melanocortin receptors, increased Agrp expression, and potential rewiring of
      brain circuits may underlie the exacerbated obesity.

PMID- 17505817
TI  - Impact of smoking abstinence on working memory neurocircuitry in adolescent daily
      tobacco smokers.
AB  - RATIONALE: Efficient function of neurocircuitry that supports working memory
      occurs within a narrow range of dopamine neurotransmission. Work in rodents has
      shown that exposure to nicotine during adolescence leads to nicotine withdrawal
      emergent alterations in cortical and subcortical dopamine neurotransmission.
      OBJECTIVES: To test for evidence that the efficiency of neurocircuitry supporting
      working memory is altered during acute smoking abstinence in adolescent daily
      tobacco smokers. MATERIALS AND METHODS: Fifty-five adolescent daily tobacco
      smokers were compared with 38 nonsmokers using functional magnetic resonance
      imaging while subjects performed a verbal working memory task. Smokers were
      studied during smoking and after 24 h of abstinence from tobacco use. RESULTS:
      Performance of a task with high working memory load in the context of smoking
      abstinence was associated with greater activation of components of the verbal
      working memory neurocircuit, including left ventrolateral prefrontal cortex and
      left inferior parietal lobe, among smokers relative to nonsmokers. During smoking
      abstinence, smokers failed to exhibit increases in functional connectivity
      between components of the working memory neurocircuit with increasing working
      memory load observed in nonsmoking adolescents and in prior studies of adults.
      CONCLUSIONS: Smoking abstinence in adolescent smokers is associated with
      reductions in the efficiency of working memory neurocircuitry and alterations in
      the functional coordination between components of the working memory
      neurocircuit. These alterations may stem from effects of nicotine exposure on
      catecholaminergic systems during adolescent development.

PMID- 17505818
TI  - Cocaine-induced sensitization is associated with altered dynamics of
      transcriptional responses of the dopamine transporter, tyrosine hydroxylase, and
      dopamine D2 receptors in C57Bl/6J mice.
AB  - RATIONALE: Behavioural sensitization is a long lasting phenomenon that has been
      proposed to be involved in drug addiction. Although the expression of cocaine
      induced sensitization has been associated with the activity of the mesencephalic
      dopaminergic neurons, little is known about the transcriptional adaptations of
      these neurons to a new challenge with cocaine long after cessation of repeated
      exposure to the drug. OBJECTIVES: We studied the time course of the mRNA levels
      of three main regulatory elements of dopaminergic transmission after a challenge
      with cocaine (15 mg/kg) that followed 21 days of withdrawal from a cocaine
      pretreatment (20 mg/kg, ip, every 2 days for 21 days) in C57Bl/6J mice. MATERIALS
      AND METHODS: Mice were placed 45 min in activity chambers and were killed 45 min,
      2 h or 24 h after the challenge injection. Dopamine transporter (DAT), D2 auto
      receptor (D2) and tyrosine hydroxylase (TH) mRNA levels were assessed by in situ
      hybridization in the ventral tegmental area and the substantia nigra compacta.
      RESULTS: As compared to vehicle challenge, cocaine challenge in vehicle
      pretreated mice induced a rapid increase (+208%) in DAT mRNA (45 min) followed by
      a delayed decrease (-70%) (24 h), while TH and D2 mRNA were both increased (+45%)
      24 h after the challenge. In cocaine pretreated mice, cocaine-induced short-term
      increase and long-term decrease in DAT mRNA levels were amplified (+328%) and
      reduced (-40%), respectively. CONCLUSIONS: Repeated exposure to cocaine alters
      the transcriptional response of DA neurons to a new cocaine challenge long after
      cessation of repeated exposure to the drug. They point to the DAT mRNA as a major
      responsive element to a new presentation of cocaine.

PMID- 17505819
TI  - Molecular imprinting of peptides and proteins in aqueous media.
AB  - Molecular imprinting has received significant attention in recent years, as it
      provides a viable method for creating synthetic receptors capable of selectively
      recognizing specific target molecules. Despite significant growth within the
      field, the majority of template molecules studied thus far have been
      characterized by their low molecular weight and insolubility in aqueous systems.
      In biological systems, molecular recognition events occur in aqueous media.
      Therefore, in order to create molecularly imprinted polymers capable of mimicking
      biological processes, it is necessary to synthesize artificial receptors which
      can selectively recognize their respective target biological macromolecules such
      as peptides and proteins in aqueous media. In this review, we discuss the
      challenges associated with the imprinting of peptides and proteins in aqueous
      media. In addition, we discuss the significant progress which has been made
      within the field.

PMID- 17505820
TI  - Postural adjustments and reaching in 4- and 6-month-old infants: an EMG and
      kinematical study.
AB  - Adequate postural control is a prerequisite for daily activities such as reaching
      for an object. However, knowledge on the relationship between postural
      adjustments and the quality of reaching movements during human ontogeny is
      scarce. Therefore we evaluated the development of the relationship between the
      kinematic features of reaching movements and the accompanying postural
      adjustments in young infants. Twelve typically developing (TD) infants were
      assessed twice, i.e. at 4 and 6 months of age, in supine and supported sitting
      position. Reaching was elicited by presenting toys in the midline at an arm
      length distance while simultaneously surface EMG-activity was recorded from
      multiple arm-, neck-, trunk- and leg muscles. Concurrently kinematics of reaching
      were recorded with an ELITE system; kinematic analysis was restricted to the
      behaviour of so-called movement units, which are sub movements of reaching
      determined with the help of peaks in the velocity profile of the hand, maximum
      movement velocity and movement duration. A computer-algorithm determined
      significant phasic muscle activity. Activity in neck and trunk muscles (postural
      activity) was related to the onset of the prime mover, which was the arm muscle
      being activated first. The results indicated that about 50% of reaching movements
      in lying and sitting infants aged 4 and 6 months were accompanied by direction
      specific postural adjustments. At 4 months variation dominated, but at 6 months a
      preference to recruit muscles in a top-down order (during sitting) and in the
      configuration of the complete pattern, i.e. the pattern in which all dorsal neck-
      and trunk muscles are activated in concert, (both conditions) emerged.
      Interestingly, the postural characteristics such as the presence of direction
      specificity, recruitment of the complete pattern and top-down recruitment, were
      related to how successful the reaching was and the kinematics of reaching. It was
      concluded that the presence of direction-specific activity is not a prerequisite
      for the emergence of reaching movements. Nevertheless, already from 4 months
      onwards a better postural control is associated with a larger success and a
      better quality of reaching.

PMID- 17505821
TI  - The influence of dose and N-acetyltransferase-2 (NAT2) genotype and phenotype on
      the pharmacokinetics and pharmacodynamics of isoniazid.
AB  - OBJECTIVE: This study evaluated the pharmacokinetics of isoniazid (INH)
      associated with optimal early bactericidal activity (EBA), defined as 90% of the
      maximum EBA (EBA(90)) and the influence of N-acetyltransferase-2 (NAT2) subtype
      on the ability of pulmonary tuberculosis (PTB) patients to reach the identified
      pharmacokinetic values after INH doses ranging from 0.2 to 10-12 mg/kg body
      weight. METHODS: INH serum concentrations and NAT2 subtype were determined during
      four studies of PTB patients in three of whom the EBA of INH was determined. The
      relationship of EBA to area under the curve (AUC) (AUC(0-infinity)) and 2-h serum
      concentrations was examined by exponential regression and fitted curves estimated
      the AUC(0-infinity) and 2-h serum concentrations at which EBA(90) was reached.
      RESULTS: EBA(90) was reached at an AUC(0-infinity) of 10.52 microg/ml per hour
      and 2-h serum concentrations of 2.19 microg/ml. An AUC(0-infinity) of 10.52
      microg/ml per hour was reached by all 66 patients receiving a 10-12 mg/kg INH
      dose and all 21 receiving 6 mg/kg, except 1 of 10 (10%) homozygous fast (FF)
      acetylators; however, at 5 mg/kg, 4 of 12 (33%) FF and 26 of 27 (96%)
      heterozygous fast (FS), but all 21 homozygous slow (SS) acetylators did so; and 1
      of 3 (33%) FF, 2 of 6 (33%) FS, but all 4 SS acetylators at dose 3 mg/kg. An INH
      2-h serum concentration of 2.19 microg/ml was reached by all 66 patients
      receiving 10-12 mg/kg and all 21 receiving 6 mg/kg, except for 2 (20%) FF
      acetylators at a dose of 5 mg/kg; however, only 3 (25%) of 12 FF acetylators, but
      26 (96%) of 27 FS acetylators, and all 21 SS acetylators reached this
      concentration; and at a dose of 3 mg/kg, 1 (33%) of 3 FF acetylators, 2 (33%) of
      6 FF, but all 4 SS acetylators. CONCLUSIONS: At a 6 mg/kg dose, all except a
      minority of FF NAT2 acetylators, achieve an INH AUC(0-infinity) and 2-h INH serum
      concentrations associated with EBA(90), as did all 4 SS acetylators receiving 3
      mg/kg. Any dose reduction below 6 mg/kg body weight will tend to disadvantage a
      significant proportion of faster acetylators, but, conversely, SS acetylators
      require only a 3 mg/kg dose to achieve a satisfactory exposure to INH.

PMID- 17505823
TI  - Over-expressing GLT1 in a gpd2Delta mutant of Saccharomyces cerevisiae to improve
      ethanol production.
AB  - We constructed two recombinant strains of Saccharomyces cerevisiae in which the
      GPD2 gene was deleted using a one-step gene replacement method to minimize
      formation of glycerol and improve ethanol production. In addition, we also over
      expressed the GLT1 gene by a two-step gene replacement method to overcome the
      redox-imbalancing problem in the genetically modified strains. The result of
      anaerobic batch fermentations showed that the rate of growth and glucose
      consumption of the KAM-5 (MATalpha ura3 gpd2Delta::RPT) strain were slower than
      the original strain, and the KAM-13 (MATalpha ura3 gpd2Delta::RPT P ( PGK ) 
      GLT1) strain, however, was indistinguishable compared to the original strain
      using the same criteria, as analyzed. On the other hand, when compared to the
      original strain, there were 32 and 38% reduction in glycerol formation for KAM-5
      and KAM-13, respectively. Ethanol production increased by 8.6% for KAM-5 and
      13.4% for KAM-13. Dramatic reduction in acetate and pyruvic acid was also
      observed in both mutants compared to the original strains. Although gene GPD2 is
      responsible for the glycerol synthesis, the mutant KAM-13, in which glycerol
      formation was substantially reduced, was able to cope and maintain osmoregulation
      and redox balance and have increased ethanol production under anaerobic
      fermentations. The result verified the proposed concept of increasing ethanol
      production in S. cerevisiae by genetic engineering of glycerol synthesis and over
      expressing the GLT1 gene along with reconstituted nicotinamide adenine
      dinucleotide metabolism.

PMID- 17505822
TI  - Chicken CD69 and CD94/NKG2-like genes in a chromosomal region syntenic to
      mammalian natural killer gene complex.
AB  - In mammals, natural killer (NK) cell C-type lectin receptors were encoded in a
      gene cluster called natural killer gene complex (NKC). The NKC is not reported in
      chicken yet. Instead, NK receptor genes were found in the major
      histocompatibility complex. In this study, two novel chicken C-type lectin-like
      receptor genes were identified in a region on chromosome 1 that is syntenic to
      mammalian NKC region. The chromosomal locations were validated with fluorescent
      in situ hybridization. Based on 3D structure modeling, sequence homology,
      chromosomal location, and phylogenetic analysis, one receptor is the orthologue
      of mammalian cluster of differentiation 69 (CD69), and the other is highly
      homologous to CD94 and NKG2. Like CD94/NKG2 gene found in teleostean fishes,
      chicken CD94/NKG2 has the features of both human CD94 and NKG2A. Unlike mammalian
      NKC, these two chicken C-type lectin receptors are not closely linked but
      separated by 42 million base pairs according to the chicken draft genome
      sequence. The arrangement of several other genes that are located outside the
      mammalian NKC is conserved among chicken, human, and mouse. The chicken NK C-type
      lectin-like receptors in the NKC syntenic region indicate that this chromosomal
      region existed before the divergence between mammals and aves.

PMID- 17505824
TI  - Cardiovascular molecular MR imaging.
AB  - INTRODUCTION: Cardiovascular molecular imaging is a rapidly evolving field of
      research, aiming to image and quantify molecular and cellular targets in vivo. MR
      imaging has some inherent properties that make it very suitable for
      cardiovascular molecular imaging. Until now, only a limited number of studies
      have been published on cardiovascular molecular imaging using MR imaging. REVIEW:
      In the current review, MR techniques that have already shown potential are
      discussed. Metabolic MR imaging can be performed by (31)P-MR spectroscopy, (23)Na
      MR spectroscopy and (1)H-MR spectroscopy; some examples are shown. Furthermore, a
      concise overview is given of several aspecific and specific contrast agents for
      cardiovascular molecular MR imaging, such as gadolinium-based contrast agents,
      iron oxide MR contrast agents and fibrin-targeted MR contrast agents. CONCLUSION:
      We expect that in the next decade currently promising MR molecular imaging agents
      will be introduced into the clinical arena to guide diagnosis and therapy of
      cardiovascular disease.

PMID- 17505825
TI  - Combination of doxorubicin and low-intensity ultrasound causes a synergistic
      enhancement in cell killing and an additive enhancement in apoptosis induction in
      human lymphoma U937 cells.
AB  - PURPOSE: Potential clinical use of ultrasound (US) in enhancing the effects of
      anticancer drugs in the treatment of cancers has been highlighted in previous
      reports. Increased uptake of drugs by the cancer cells due to US has been
      suggested as a mechanism. However, the precise mechanism of the enhancement has
      not yet been elucidated. Here, the combined effects of low-intensity pulsed US
      and doxorubicin (DOX) on cell killing and apoptosis induction of U937 cells, and
      mechanisms involved were investigated. METHODS: Human myelomonocytic lymphoma
      U937 cells were used for the experiments. Experiments were conducted in 4 groups:
      (1) non-treated, (2) DOX treated (DOX), (3) US treated (US), and (4) combined
      (DOX + US). In DOX +US, cells were exposed to 5 microM DOX for 30 min and
      sonicated by 1 MHz pulsed US (PRF 100 Hz, DF 10%) at intensities of 0.2-0.5
      W/cm(2) for 60 s. The cells were washed and incubated for 6 h. The viability was
      evaluated by Trypan blue dye exclusion test and apoptosis and incorporation of
      DOX was assessed by flow cytometry. Involvement of sonoporation in molecular
      incorporation was evaluated using FITC-dextran, hydroxyl radical formation was
      measured by electron paramagnetic resonance-spin trapping, membrane alteration
      including lipid peroxidation and membrane fluidity by DOX was evaluated using cis
      parinaric acid and perylene fluorescence polarization method, respectively.
      RESULTS: Synergistic enhancement in cell killing and additive enhancement in
      induction of apoptosis were observed at and above 0.3 W/cm(2). No enhancement was
      observed at 0.2 W/cm(2) in cell killing and induction of apoptosis. Hydroxyl
      radicals formation was detected at and above 0.3 W/cm(2). The radicals were
      produced more in the DOX + US than US alone. Incorporation of DOX was increased
      13% in DOX + US (vs. DOX) at 0.5 W/cm(2). Involvement of sonoporation for
      increase of drug uptake was suggested by experiment using FITC-labeled dextran.
      We made the hypothesis that DOX treatment made the cells weaken against the
      mechanical effect of the US. Although treatment of DOX at 5 microM for 30 min did
      not affect lipid peroxidation and fluidity of cell membrane significantly, higher
      concentration and longer treatment of DOX induced the significant alteration of
      cell membrane. CONCLUSION: Mechanisms of enhancements could be (1) increase in
      incorporation of the DOX by US involved with sonoporation, (2) enhancement of the
      cavitation by DOX. Cavitation is required for the enhancement of the effect of
      DOX. Although the precise involvement of the membrane modifications by DOX in the
      enhancement remains to be elucidated, they could be involved in the latent
      effects.

PMID- 17505826
TI  - A small molecule pan-Bcl-2 family inhibitor, GX15-070, induces apoptosis and
      enhances cisplatin-induced apoptosis in non-small cell lung cancer cells.
AB  - PURPOSE: Overexpression of Bcl-2 family members as well as deregulated apoptosis
      pathways are known hallmarks of lung cancer. Non-small cell lung cancer (NSCLC)
      cells are typically resistant to cytotoxic chemotherapy and approaches that alter
      the balance between pro-survival and pro-death Bcl-2 family members have shown
      promise in preclinical models of NSCLC. METHODS: Here we evaluated the effects of
      a novel pan-Bcl-2 inhibitor GX15-070 on NSCLC survival and when combined with
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as well as
      traditional cytotoxic agents. GX15-070 is a small molecule agent that binds anti
      apoptotic Bcl-2 proteins and interferes with their ability to interact with pro
      apoptotic proteins. We evaluated the effect of GX15-070 and correlated the effect
      on EGFR status as well as Bcl-2 family protein expression. RESULTS: We show that
      GX15-070 can disrupt Mcl-1:Bak interactions in lung cancer cells. We identified
      differential sensitivity of a panel of lung cancer cells to GX15-070 and no clear
      relationship existed between EGFR status or Bcl-2 family protein expression and
      sensitivity to GX15-070. GX15-070 could induce apoptosis in a subset of lung
      cancer cell lines and this correlated with the effects on cell viability. GX15
      070 combined with gefitinib was synergistic in a cell line dependent on EGFR for
      survival but GX15-070 could not reverse resistance to gefitinib in cell lines not
      dependent on EGFR for survival. Finally, we observed synergy between GX15-070 and
      cisplatin in NSCLC cells. CONCLUSIONS: Based on these results, GX15-070 can
      trigger apoptosis in NSCLC cells and can enhance chemotherapy-induced death.
      These data suggest that clinical trials with GX15-070 in combination with
      cytotoxic chemotherapy are indicated.

PMID- 17505827
TI  - A phase I and pharmacokinetic study of sunitinib administered daily for 2 weeks,
      followed by a 1-week off period.
AB  - PURPOSE: Sunitinib, an oral multitargeted tyrosine kinase inhibitor that inhibits
      VEGFR, PDGFR, FLT3, KIT, and RET, is currently approved for the treatment of
      imatinib-refractory GIST and advanced renal cell carcinoma at a dose of 50 mg
      daily for 4 weeks followed by a 2-week off period (4/2 schedule). This trial was
      performed to investigate the safety, tolerability, and pharmacokinetics of
      sunitinib 50 mg daily for 2 weeks followed by a 1-week off period (2/1 schedule).
      EXPERIMENTAL DESIGN: Twelve patients with advanced refractory malignancies were
      treated with sunitinib on the 2/1 schedule. Intensive safety monitoring included
      serial measurements of left ventricular ejection fraction (LVEF). Extensive
      pharmacokinetic sampling was performed on days 1 and 14 of course 1, and on day
      14 of courses 2 and 3 to evaluate sunitinib and the SU12662 metabolite. RESULTS:
      Twelve patients received a total of 50 courses with an average (+/-SD) off-drug
      period of 11.5 +/- 5.7 days. Two patients experienced DLT: one patient had
      asymptomatic grade 4 elevations in lipase and amylase, and another patient had an
      asymptomatic grade 2 decline in LVEF in course 1. In total, five patients
      demonstrated asymptomatic grade 2 declines in LVEF. Other principal effects were
      similar to previous experience with sunitinib, including fatigue,
      myelosuppression, skin discoloration, and gastrointestinal effects.
      Pharmacokinetic studies revealed no significant accumulation of sunitinib or
      SU12662. One patient with papillary thyroid cancer developed a partial response,
      and was on study for 16 courses, followed by an additional 18 courses on a
      continuation protocol. CONCLUSIONS: The 2/1 schedule of sunitinib 50 mg was
      tolerable, and no significant drug accumulation was demonstrated. The safety
      profile on this schedule was consistent with the safety profile of sunitinib when
      administered on a 4-week on, 2-week off schedule.

PMID- 17505828
TI  - Global dynamics of microbial competition for two resources with internal storage.
AB  - We study a chemostat model that describes competition between two species for two
      essential resources based on storage. The model incorporates internal resource
      storage variables that serve the direct connection between species growth and
      external resource availability. Mathematical analysis for the global dynamics of
      the model is carried out by using the monotone dynamical system theory. It is
      shown that the limiting system of the model basically exhibits the familiar Lotka
      Volterra alternatives: competitive exclusion, coexistence, and bi-stability, and
      most of these results can be carried over to the original model.

PMID- 17505829
TI  - Evidence-based review of biologic markers as indicators of disease progression
      and remission in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease
      characterised by inflammation resulting in structural joint damage and functional
      disability. Tumour necrosis factor-alpha (TNFalpha) is a pivotal mediator and
      driver of inflammation in RA. Inflammation is closely related to the production
      of C-reactive protein (CRP), and a close correlation exists between serum CRP and
      TNFalpha levels. CRP levels are therefore a convenient, objective biomarker of
      disease activity. CRP correlates closely with changes in inflammation/disease
      activity, radiological damage and progression and functional disability.
      Identification of TNFalpha as a driver of RA progression has led to the
      introduction of TNFalpha-blocking agents and, subsequently, improvement of
      disease management. TNFalpha-blocking agents provide rapid, profound and
      sustained suppression of disease activity in correspondence with a marked
      reduction in CRP levels. A reduction in CRP level correlates closely with the
      positive clinical response to TNFalpha-blocking therapy. Thus, CRP levels can be
      used to predict, assess and monitor response to treatment with TNFalpha-blocking
      agents, and may be helpful in determining the optimal TNFalpha-blocker dosage.
      Given the close correlation between inflammation and disease progression and the
      relation between inflammation and CRP, the latter, if used effectively in
      clinical practice, may be means to identify patients likely to progress rapidly
      and who require intensive anti-TNFalpha therapy. The purpose of this review is to
      identify how CRP levels may be useful for monitoring the effect of therapy on
      halting disease progression and why monitoring CRP levels at baseline and after
      treatment should become a routine part of clinical practice.

PMID- 17505830
TI  - Diffusion tensor MR imaging of the cervical spinal cord in patients with multiple
      sclerosis.
AB  - Our purpose was to evaluate the ability of diffusion tensor imaging (DTI) to
      characterize cervical spinal cord white matter (WM) in patients with multiple
      sclerosis (MS). DTI were obtained in 21 MS patients and 21 control subjects (CS).
      Regions of interest (ROIs) were placed at C2/3, C3/4, and C4/5 within the right,
      left, and dorsal (WM) to calculate fractional anisotropy (FA) and the apparent
      diffusion coefficient (ADC). Measurements in plaques and normal-appearing white
      matter (NAWM) of MS patients were compared with mean FA and ADC of WM in CS. FA
      was significantly lower in all regions in MS patients than in CS. ADC was
      significantly higher in all regions in MS patients than in CS except for in the
      dorsal WM at C2/3 and the bilateral WM at C4/5. The mean FA was 0.441 for plaques
      and 0.542 for NAWM, as compared with 0.739 in CS. The mean ADC was 0.810 x 10(-3)
      mm(2)/s for plaques and 0.722 x 10(-3) mm(2)/s for NAWM, as compared with 0.640 x
      10(-3) mm(2)/s for CS. FA and ADC showed significant differences between plaques,
      NAWM and control WM(P < 0.01).

PMID- 17505831
TI  - [Introduction to the topic: medial evaluation of severely handicapped and blind
      persons in legislation].

PMID- 17505832
TI  - [Determination of visual function in legal assessment].
AB  - For the determination of visual function an objective assessment is essential.
      Basic ophthalmologic examinations such as measurement of visual acuity and
      perimetry are dependent on patient statements. If the patient is not being able
      to provide adequate answers, as is the case for small children or mentally
      retarded patients, or also if the accuracy of the patient's statements is
      doubtful or simulation or aggravation is suspected, the denoted function in the
      evaluation of visual acuity has to be checked on consistency using different
      examination methods, and the results of objective functional tests, such as
      electrophysiology and morphological features, have to be taken into account.

PMID- 17505833
TI  - [Errors and difficulties in the assessment of severely handicapped and blind
      persons].
AB  - The assessment of ophthalmological examination reports in social law is usually
      based on subjective statements by the petitioner made towards his
      ophthalmologist. Insufficient consideration of objective results as well as the
      limited experience of the officials in charge may lead to errors. An analysis of
      patients for consideration as legally blind in Baden, Germany, between 1980-1999,
      based upon 2,265 doubtful applications resulted in 33.3% false estimates by the
      patient's ophthalmologist. The reason, in the vast majority of cases, was
      misjudgment involving visual field defects or even missing manual-kinetic
      Goldmann perimetry. It may be assumed that this is also true for petitions in
      legislation for severely handicapped persons, particularly because the officials
      in charge are rarely ophthalmologists.

PMID- 17505834
TI  - [Fundamentals for the medical evaluation of handicapped people in legislation].
AB  - In claims from social law, evaluation by the treating physician is often
      mandatory. He is obliged to provide information at the request of the social
      insurance carrier. Ophthalmologists are required to independently and objectively
      assess medical conditions, apart from a routine visit, and pass the data on to
      the consultants at the pension office in a understandable way. Functional
      impairment must be explained on the basis of morphology, diagnosis and
      examination results so that it becomes impartially comprehensible. Basically,
      examination results must be presented according to the standards of medical
      evaluation, such as DIN 58220 visual acuity testing and visual fields analogous
      to manual-kinetic perimetry by Goldmann perimeter or approved comparable methods
      of visual field testing. Results that are not compliant with the official
      standards need to be identified accordingly.

PMID- 17505835
TI  - A rat model of childhood diet-induced obesity: Roux-en-Y gastric bypass induced
      changes in metabolic parameters and gastric peptide ghrelin.
AB  - Childhood morbid obesity is reaching epidemic proportions. Roux-en-Y gastric
      bypass (RYGB) results in many metabolic alterations, including changes in glucose
      and lipid metabolism, and changes in levels of the gastric hormone, ghrelin. As
      more children are undergoing RYGB, an animal model would be beneficial to further
      study RYGB and its subsequent metabolic effects. DIO Sprague Dawley rats
      underwent RYGB, sham jejunojejunostomy (SH), or no operation (HFC) after 6 weeks
      of high-fat diet. Non-obese rats fed standard chow (SC) were a final control
      group. Animals were post-operatively fed standard chow for 7 days before
      sacrifice. At sacrifice, venous blood and gastric mucosa was collected for
      metabolic parameters and ghrelin determination. RYGB rats weighed less than SH
      and HFC (361 +/- 8.8 vs. 437 +/- 9.3 and 443 +/- 6.2 g, P < 0.05). Compared to
      HFC, RYGB animals had decreased plasma glucose (292 +/- 23 vs. 141 +/- 10 mg/dL),
      cholesterol (80 +/- 12 vs. 45 +/- 5 mg/dL), triglycerides (138 +/- 37 vs. 52 +/-
      7 mg/dL), HDL (43 +/- 5 vs. 20 +/- 3 mg/dL), and free fatty acids (0.72 +/- 0.14
      vs. 0.23 +/- 0.02 mEq/L), all P < 0.05. Plasma ghrelin increased in RYGB rats
      compared to SC and HFC (116.22 +/- 32.27 vs. 31.60 +/- 2.66 and 31.75 +/- 0.75
      pg/mL, P < 0.05). In a rat model of RYGB, we demonstrated improved metabolic
      parameters and increased plasma and gastric mRNA ghrelin levels. The rat model
      for RYBG appears to be a reasonable model for future study of the cellular and
      molecular regulatory pathways of obesity and its surgical treatment.

PMID- 17505836
TI  - Biochemical, biomechanical and histological properties of osteoarthritic porcine
      knee cartilage: implications for osteochondral transplantation.
AB  - INTRODUCTION: Cartilage lesions of the knee joint are frequently observed during
      arthroscopy and when surgical intervention is required, osteochondral autograft
      procedures are an established method of treatment. Frequently lesions are located
      on the medial femoral condyle (MFC), and typical donor locations for
      osteochondral grafts include the medial and lateral patellar groove. This
      technique provides good results, even when the quality of cartilage transplanted
      from an osteoarthritic joint is doubtful. This study characterizes biological,
      biomechanical and histological properties of cartilage explants from the patellar
      groove harvested from osteoarthritic joints. MATERIALS AND METHODS: Cylindrical
      cartilage explants were harvested from the arthritic areas of the MFC as well as
      normal appearing regions of the medial and lateral patellar groove from porcine
      joints revealing various grades of osteoarthritis. Matrix synthesis rates were
      determined, and explants were investigated by mechanical testing and histology.
      RESULTS: Articular cartilage obtained from the typical donor areas of the medial
      and lateral patellar groove provided constant enhanced material properties,
      matrix synthesis rates and histological appearance compared to samples from the
      arthritic lesions of the MFC, even in joints with end-stage osteoarthritis of the
      MFC. No significant difference was found between patellar groove cartilage
      samples harvested from joints with different stages of osteoarthritis.
      CONCLUSION: Our findings demonstrate that healthy appearing cartilage from the
      patellar groove does not undergo significant alterations in material properties
      due to the arthritic milieu present in osteoarthritic joints. Accordingly these
      locations provide a source of functional tissue for transplant procedures even in
      joints with end-stage osteoarthritis.

PMID- 17505837
TI  - Ankle stiffness after Bosworth fracture dislocation of the ankle.
AB  - PURPOSE: The purpose of this study is to review the result of patients with
      Bosworth fracture dislocation of ankle. TYPE OF STUDY: Retrospective case series.
      METHODS: Four patients with Bosworth fracture-dislocation of ankle are evaluated
      clinically and radiologically. RESULT: All four cases have failed initial closed
      reduction of the ankle and open reduction is required. Three patients with
      delayed presentation suffered from post-traumatic ankle stiffness and
      subsequently developed ankle degeneration. CONCLUSION: Early recognition and
      prompt reduction of the dislocated ankle is important in case of Bosworth
      fracture dislocation in order to prevent late complication. Closed reduction of
      dislocated ankle is usually not helpful and repeated attempts may be harmful.
      Emergency operation of open reduction and internal fixation is usually required
      to reduce the ankle joint without delay.

PMID- 17505838
TI  - Arthroscopic implantation of a three dimensional scaffold for autologous
      chondrocyte transplantation.
AB  - The arthroscopic M-ACT technique is applicable for defects at the femoral condyle
      up to 5 cm(2). The size of the defect has to be assessed with a specific scaled,
      percutaneously inserted needle. Then an 8 mm water-stop-cannula is positioned in
      a suprameniscal portal. The chondrocyte seeded matrix is trimmed to size the
      defect. The scaffold is introduced in the joint through the cannula and placed
      into the defect with a blunt arthroscopic grasp instrument to prevent damage of
      the scaffold. Then a specific drill guide is inserted through an additional
      anteromedial portal to place it on the scaffold in a perpendicular angle. The
      position of the drill guide should not be changed during the next two steps. It
      may be helpful to hold the matrix in place with a probe inserted through the
      cannula. A 1.5 mm K-wire is drilled at least 16 mm into the subchondral bone.
      Then the biodegradable pin (length 16 mm) is placed in the drill guide and
      carefully hammered into the subchondral bone. The joint is flexed so that the
      drill guide can be placed on the posterior end of the scaffold. Another hole is
      drilled with the K-wire and a second pin is inserted. Finally the stability of
      the matrix is tested with a probe and the joint is mobilized.

PMID- 17505839
TI  - Complete osseous avulsion of the adductor longus muscle: acute repair with three
      fiberwire suture anchors.
AB  - BACKGROUND: An acute tear of the adductor longus tendon is a seldom injury. A
      proximal osseous avulsion of this tendon has never been reported in literature.
      METHODS: Acute repair (refixation) of the osseous avulsion with three suture
      anchors. RESULTS: Physical examinations 3, 6 and 24 months following the injury
      revealed no evidence of tenderness over the adductor muscle group, and range of
      motion was equal to the contra lateral hip. Manual muscle strength testing was
      5/5 with resisted adduction and identical to the opposite side. The patient
      returned to his previous level of sports. CONCLUSION: This case seems to be the
      first description of a proximal tendon rupture of the adductor longus muscle with
      an isolated osseous avulsion. Surgical treatment of this injury with the use of
      three fiberwire suture anchorstrade mark was successful. STUDY DESIGN: Case
      report.

PMID- 17505840
TI  - A comparative study of topical natural ergot alkaloids on the intraocular
      pressure and aqueous humor dynamics in oclular normotensive and alpha
      chymotrypsin-induced ocular hypertensive rabbits.
AB  - BACKGROUND: Although it has been suggested that ergot derivatives may play a role
      in antiglaucoma therapy, little attention has been paid to the ocular hypotensive
      action of these drugs. Having previously reported that topical natural ergot
      alkaloids ergocristine alpha-ergocryptine and ergocornine dose-dependently reduce
      intraocular pressure in ocular normotensive and alpha-chymotrypsin-induced ocular
      hypertensive rabbits, the aim of the present work was to compare the effect of
      ergocristine, alpha-ergocryptine and ergocornine on the intraocular pressure and
      aqueous humor dynamics in ocular normotensive and alpha-chymotrypsin-induced
      ocular hypertensive rabbits, in order to further explore the ocular actions of
      these compounds. METHODS: Experiments were conducted in albino ocular
      normotensive and hypertensive rabbits by intracameral injection of alpha
      chymotrypsin. Intraocular pressure responses to drug vehicle and seven different
      doses of topical natural ergot alkaloids were examined, in order to obtain dose
      response relationships for comparing the intraocular pressure-lowering effect and
      potency of these drugs. Tonographies were also performed to ascertain the actions
      of natural ergot alkaloids on aqueous humor dynamics. RESULTS: All natural ergot
      alkaloids tested reduced intraocular pressure in a dose-related fashion. The
      ocular hypotensive effect was greater in alpha-chymotrypsin-induced ocular
      hypertensive rabbits for the three compounds tested. All natural ergot alkaloids
      tested decreased both tonographic outflow facility and, to a greater extent,
      aqueous humor inflow in ocular normotensive and in alpha-chymotrypsin-induced
      ocular hypertensive rabbits. CONCLUSION: Taken together, our data suggest that
      these compounds decrease both tonographic outflow facility and, to a greater
      extent, aqueous humor inflow, which explains their final effect in ocular
      normotensive and in alpha-chymotrypsin-induced ocular hypertensive rabbits.
      Reductions in aqueous humor inflow observed after topical application of natural
      ergot alkaloids in alpha-chymotrypsin-induced ocular hypertensive rabbits can
      only be explained by a marked inhibition of active secretion of aqueous humor,
      since processes involved in aqueous humor formation may probably be altered after
      alpha-chymotrypsin injection.

PMID- 17505842
TI  - Induction of Fas (CD95/APO-1) ligand is essential for p53-dependent apoptosis in
      an in vitro renal carcinoma model system.
AB  - PURPOSE: The Fas/CD95/APO-1 ligand (FasL) is a death cytokine that binds to cell
      surface Fas/CD95/APO-1 receptor, yet a possible role of FasL expression in p53
      dependent apoptosis is not fully understood in many human malignancies, including
      renal carcinoma. METHODS: By Northern blot and Western blot analyses, we
      determined the effect of p53 on the FasL and Fas receptor expression. To do this,
      we employed an in vitro renal carcinoma model system that was previously
      established by stably co-transfecting a temperature-sensitive mutant allele of
      the p53 tumor suppressor (ts-p53) with either the c-Myc oncogene or adenovirus
      E1A oncogene in baby rat kidney (BRK) epithelial cells. The ts-p53 is activated
      only at a permissive temperature. The transactivation activity of p53 was
      assessed by luciferase reporter assays. The sub-G1 cell population in the cell
      cycle representing apoptotic cell death was measured by flow cytometric analysis.
      RESULTS: We found that the level of endogenous FasL, but not Fas receptor, was
      increased at a permissive temperature with delayed kinetics when compared with
      p21WAF1 expression, but was coincident with p53-induced apoptosis, whereas an
      apoptosis-defective mutant p53, which lacks the PxxP region (P: Proline, x: any
      amino acid), failed to induce FasL expression and hence apoptosis. Notably, p53
      induced apoptosis was completely blocked by overexpressing a dominant negative
      inhibitor of the FADD/Mort-1, a pro-apoptotic adaptor that lies immediately
      downstream of the FasL/Fas receptor. CONCLUSIONS: These results suggest that the
      FasL is a critical downstream effector of p53-dependent apoptosis in a cultured
      BRK renal carcinoma model system.

PMID- 17505841
TI  - Serial left-ventricular biopsy sampling using a minimally invasive trans-thoracic
      approach in adult dogs.
AB  - Myocardial biopsies are an increasingly important tool to unravel the molecular
      mechanisms of cardiac disease. We evaluate a novel minimally invasive trans
      thoracic approach for left-ventricular (LV) intra-mural biopsies, which enables
      repetitive individual sampling in adult dogs. Forty three generally anaesthesised
      dogs were studied during sinus rhythm (SR, control) and multiple times after the
      induction of volume overload hypertrophy (complete atrioventricular block [AVB]).
      Through a small cutaneous incision, an automatic biopsy needle was advanced into
      the apicolateral LV, guided by fluoroscopy. Electrocardiography (ECG), LV
      pressure and echocardiography served to monitor the procedure. One hundred eighty
      eight intra-mural LV biopsies were obtained in 82 serial experiments (usually SR,
      1, 2 and 6 weeks AVB) with a maximum of 8 repeated biopsies. All biopsies (
      approximately 10 mm(3)) were suitable for simultaneous application of different
      cell-biological (light and electron microscopy, immunohistochemistry) and
      molecular techniques (PCR, Western blotting). In chronic experiments, repeated
      biopsy sampling did not influence haemodynamics, mechanics, electrocardiographic
      parameters or myocardial remodelling during SR or AVB. The rate of significant
      complications was as low as 4% of experiments. Minimally invasive sampling of LV
      needle biopsies enables serial assessment of myocardial remodelling using
      different molecular techniques in individual animals. The technique is safe and
      has no long-term effects on cardiac function or structure.

PMID- 17505843
TI  - In situ measurement of pH in the secreting canaliculus of the gastric parietal
      cell and adjacent structures.
AB  - The gastric H(+)/K(+)-ATPase is located within an infolding (secretory
      canaliculus) of the apical plasma membrane of gastric parietal cells. Our aim was
      to measure the pH values in the cytosol and canaliculus of the acid-secreting
      parietal cell and the adjacent gland lumen in situ. We used ultrafine double
      barreled tip-sealed microelectrodes at high acceleration rates for intracellular
      and canalicular measurements. Immunohistochemical staining of the parietal cells
      was used to identify the track of the electrode and to estimate the position of
      the electrode tip at the time of the last intracellular measurement. En route to
      the deepest regions of the mucosa, where the average gland lumen pH was
      approximately 3, and on advancing in steps of 2 mum, the electrode entered the
      cytosol of the parietal cells, where the pH value was 7.4. Advancing the
      electrode further resulted, in several instances, in a sharp decrease in pH to an
      average value of 1.7 +/- 0.2, which we interpreted as the measurement within the
      canaliculus. When the electrode was advanced even further, the pH reading
      returned to the cytosolic value. From the difference in pH between the secreting
      canaliculus and the adjacent gland lumen, we concluded that the released acid was
      immediately buffered. Thus, the only cellular structure directly exposed to the
      highly acidic canalicular content is the apical membrane forming the canaliculus
      in the parietal cell.

PMID- 17505844
TI  - Dendritic projections of different types of octopaminergic unpaired median
      neurons in the locust metathoracic ganglion.
AB  - Octopaminergic dorsal unpaired median (DUM) neurons of locust thoracic ganglia
      are important components of motor networks and are divided into various sub
      populations. We have examined individually stained metathoracic DUM neurons,
      their dendritic projection patterns, and their relationship to specific
      architectural features of the metathoracic ganglion, such as longitudinal tracts,
      transverse commissures, and well-defined sensory neuropils. The detailed
      branching patterns of individually characterized DUM neurons of various types
      were analyzed in vibratome sections in which architectural features were revealed
      by using antibodies against tubulin and synapsin. Whereas DUM3,4,5 and DUM5
      neurons (the group innervating leg and "non-wing-power" muscles) had many ventral
      and dorsal branches, DUM1 and DUM3,4 neurons (innervating "wing-power" muscles)
      branched extensively only in dorsal areas. The structure of DUM3 neurons differed
      markedly from that of the other DUM neurons examined in that they sent branches
      into dorsal areas and had differently structured side branches that mostly
      extended laterally. The differences between the branching patterns of these
      neurons were quantified by using currently available new reconstruction
      algorithms. These structural differences between the various classes of DUM
      neurons corresponded to differences in their function and biophysical properties.

PMID- 17505845
TI  - [DNA ploidy and proliferative activity in salivary gland tumours].
AB  - DNA ploidy and S-Phase fraction (SPF) of 279 salivary gland tumours were analysed
      using high-resolution DNA flow cytometry. All 229 benign neoplasms were diploid
      while 12 of 50 malignant tumours showed cell populations with aneuploid DNA
      content. The SPF values of diploid malignancies were significantly higher if
      compared with pleomorphic adenomas but did not differ from that of the
      zystadenolymphoma (Warthin tumour) group. While aneuploidy represents a distinct
      indicator of malignancy SPF values are of minor relevance for dignity assessment
      in salivary gland tumours.

PMID- 17505846
TI  - [Facial aesthetics Part II - effect of symmetric and asymmetric modulations of
      the orbital region].
AB  - The aim of the present study was to assess the impact of standardised computer
      manipulated changes to images of the orbital region. Judges (n=250) ranked each
      image for attractiveness on a visual-analogue-scale. The images were thereby
      classified into different clusters according to their ratings of attractiveness.
      These clusters were highly significantly different (p<0.001). The degree of
      negative impact of changes to the orbital region on facial attractiveness
      increased significantly from lateral to medial and from cranial to caudal. Small
      asymmetrical or symmetrical lateral variations did not influence attractiveness
      negatively.

PMID- 17505847
TI  - [Allergic fungal sinusitis, fungus ball and invasive sinonasal mycosis - three
      fungal-related diseases].
AB  - BACKGROUND: Three different fungal-related clinical pictures have to be
      differentiated in the paranasal sinuses: allergic fungal sinusitis, fungus ball
      and invasive sinonasal mycosis. PURPOSE: A morphological reevaluation of fungal
      related diseases of the paranasal sinuses as well as a retrospective analysis of
      their clinical parameters was performed. PATIENTS AND METHODS: 86 patients with
      patho-histological proven fungal-related disease of the nasal sinuses were
      enclosed in this study. Reevaluation and correlation of clinical and histological
      parameters were conducted on routine material (HE, PAS and Grocott) according to
      the modern morphological definitions. RESULTS: Invasive sinonasal mycosis was
      seen in 22 cases, eleven male and eleven female, mean age 57 years (22 to 84
      years). It was significantly related (nine out of 22 patients, 41%) to
      immunocompromising conditions: three patients had diabetes mellitus type II, five
      had have a radiation therapy due to carcinoma and one patient suffered from
      bacterial endocarditis. A fungus ball was diagnosed in 60 patients, 26 male, 34
      female, mean age 54 years (22-88 years). An immunocompromising condition was seen
      in nine out of 60 patients (15%). Causes for immune impairment were diabetes
      mellitus (two patients), radiation therapy due to carcinoma (four patients),
      myocarditis (one patient) and chronic hepatitis (two patients). Allergic fungal
      sinusitis was recorded in four patients, three male, one female, mean age 43
      years (17-63 years). No immunosuppression was diagnosed. CONCLUSIONS: Despite the
      fact that allergic fungal sinusitis is the most common fungal disease of the
      paranasal sinuses, it is not well known among physicians and pathologists and
      therefore underrepresented within the diagnoses of paranasal infections. The term
      "aspergilloma" is imprecise and does not represent a clear diagnosis. A further
      differentiation in "fungus ball" (without invasion) and "invasive sinonasal
      mycosis" is required. The three groups of fungal-related sinusitis occur at
      different ages. Allergic fungal sinusitis is common among young adults. An
      immunocompromising condition is a prerequisite for an invasive sinonasal mycosis.

PMID- 17505848
TI  - [Facial aesthetics part I - the significance of the triangle of yarbus].
AB  - When humans observe a face, the eyes, mouth and nose regions are the preferred
      targets of the centre of gaze, with the outlines of eye position recordings
      approximating a triangle with vertices located in the centre of the eyes and
      mouth [31]. We studied the significance of cutaneous asymmetries inside and
      outside the Yarbus triangle on the basis of the assessment of digitally
      manipulated images by 201 independent judges. We show that certain facial
      variations (such as naevi) are more attractive when asymmetrical than symmetrical
      (p<0,001). They appear more attractive when located laterally rather than
      medially, particularly so when located outside the Yarbus triangle as compared to
      inside it (p<0,001). The significance of facial symmetry increases significantly
      when approaching the Yarbus triangle or the midline, respectively.

PMID- 17505849
TI  - Increasing utilization of computed tomography in the pediatric emergency
      department, 2000-2006.
AB  - The objective of this study is to characterize changes in computed tomography
      (CT) utilization in the pediatric emergency department (ED) over a 6-year period.
      CT scans ordered on pediatric (ages 0 to 17 years) ED patients from July 2000 to
      July 2006 were analyzed in five groups: head, cervical spine, chest, abdomen, and
      miscellaneous. Pediatric ED patient volume and triage acuity scores were
      determined. There were 6,073 CT scans performed on 4,138 pediatric patients in
      the ED during the study period. During this same period, 78,932 pediatric
      patients were evaluated in the ED. From 2000 to 2006, pediatric ED patient volume
      increased by 2%, while triage acuity remained stable. During this same period,
      head CT increased by 23%, cervical spine CT by 366%, chest CT by 435%, abdominal
      CT by 49%, and miscellaneous CT by 96%. Increases in CT utilization were most
      pronounced in adolescents ages 13 to 17 years. Increases in CT utilization in
      this age group met or exceeded increases seen in the adult population. In
      children less than 13 years of age, increases were substantially smaller.
      Pediatric ED CT utilization particularly in the adolescent population has
      increased at a rate far exceeding the growth in ED patient volume, mimicking the
      adult trend. This increase has occurred despite considerable discussion in the
      medical literature about the radiation risks of CT in the pediatric population
      and may reflect increased availability of CT, improvements in CT diagnostic
      capabilities, and increased desire on the part of physicians and patients for
      diagnostic certainty. Whether this increased utilization results in improved
      patient outcomes is uncertain and deserves further study.

PMID- 17505850
TI  - Role of Drosophila gene dunc-115 in nervous system.
AB  - Axonal guidance signals are transduced through growth cone surface receptors to
      the interior leading to changes of actin dynamics and actin binding proteins,
      which are critical in determining the outcome of actin cytoskeleton
      reorganization. We report here the characterization of the Drosophila actin
      binding protein abLIM/Unc-115 homolog Dunc-115 and its role in the nervous
      system. Three Dunc-115 isoforms are identified as Dunc-115L, M and S,
      respectively. While Dunc-115L is a canonical homolog of Unc-115 with four LIM
      domains and one villin headpiece domain, Dunc-115M and S are novel isoforms
      without counterparts in other species. Our molecular modeling shows Dunc-115L is
      likely to bind to actin. Mutant analysis reveals that Dunc-115 is involved in
      axonal projection in both the visual and central nervous system.

PMID- 17505851
TI  - Beyond habitat requirements: individual fine-scale site fidelity in a colony of
      the Galapagos sea lion (Zalophus wollebaeki) creates conditions for social
      structuring.
AB  - Site fidelity has been widely discussed, but rarely been related explicitly to a
      species' social context. This is surprising, as fine-scale site fidelity
      constitutes an important structural component in animal societies by setting
      limits to an individual's social interaction space. The study of fine-scale site
      fidelity is complicated by the fact that it is inextricably linked to patterns of
      habitat use. We here document fine-scale site fidelity in the Galapagos sea lion
      (Zalophus wollebaeki) striving to disentangle these two aspects of spatial
      behaviour. Regardless of sex and age, all individuals used small, cohesive home
      ranges, which were stable in size across the reproductive and non-reproductive
      season. Home ranges showed a large individual component and did not primarily
      reflect age- or sex-specific habitat requirements. Site specificity could be
      illustrated up to a resolution of several metres. Long-term site fidelity was
      indicated by home range persistence over 3 years and the degree of site fidelity
      was unaffected by habitat, but showed seasonal differences: it was lower between
      reproductive and non-reproductive periods than between reproductive seasons. We
      further examined static and social interaction within mother-offspring pairs,
      which constitute a central social unit in most mammalian societies. Regardless of
      the occupied habitat type, adult females with offspring had smaller home range
      sizes than non-breeding females, demonstrating the importance of spatial
      predictability for mother-offspring pairs that recurrently have to reunite after
      females' foraging sojourns. While social interaction with the mother dropped to
      naught in both sexes after weaning, analysis of static interaction suggested
      female-biased home range inheritance. Dispersal decisions were apparently not
      based on habitat quality, but determined by the offspring's sex. We discuss the
      implication of observed fine-scale site fidelity patterns on habitat use,
      dispersal decisions and social structure in colonial breeding pinnipeds.

PMID- 17505852
TI  - Complications of colonic stenting: a pictorial review.
AB  - Surgical resection of colorectal carcinoma is the only curative treatment
      currently available. In the elective setting peri-operative mortality is low and
      refinements in surgical technique and peri-operative care have resulted in high
      primary anastamosis rates and progressively reduced postoperative morbidity. In
      those presenting with large bowel obstruction the mortality and morbidity remains
      high. Many of those undergoing surgery will have incurable disease and a short
      life expectancy. Increasingly self-expanding metal stents are being deployed as
      either a 'bridge to surgery' or for palliation. This review covers the imaging
      appearances, detection and management of complications of colonic stenting.

PMID- 17505853
TI  - Mucocele of the appendix on screening CT colonography: a case report.

PMID- 17505854
TI  - Epidemiology of urban trauma deaths: a comprehensive reassessment 10 years later.
AB  - BACKGROUND: We conducted a comprehensive analysis of the epidemiology of trauma
      deaths in our urban county during a one-year period a decade ago. In the interim
      we have implemented a statewide trauma system, initiated a number of injury
      prevention programs, and have had a major public effort to reduce drug traffic
      and related gangs. Consequently, we have reassessed the regional trauma mortality
      to ascertain the impact of these measures and to search for new injury patterns.
      METHODS: Trauma deaths occurring within our urban county from January 1 through
      December 31, 2002 were reviewed for mechanism, demographics, and cause of fatal
      injury; cases were identified using death certificates from the Colorado
      Department of Public Health. We compared these data to the trauma fatalities
      occurring during 1992. RESULTS: During the 2002 study period, there were 420
      injury-related deaths. Most of the patients were men (296 patients, 70%), with a
      mean age of 47.3 years (median age, 42 years). The three predominant mechanisms
      of fatal injury were transport-related (180 patients, 43%), intentional (99
      patients, 24%), and falls (86 patients, 20%). Comparison between 1992 and 2002
      showed significant increases in the percentage of transport-related and fall
      related deaths, and a significant reduction in intentional fatal injuries. There
      was also a shift in the percentage of deaths occurring in the first 24 h to
      delayed times. The death rate per capita in Denver County declined from 0.081 in
      1992 to 0.060 in 2002. CONCLUSIONS: Along with a decrease in the per capita death
      rate, the major mechanisms of patient's deaths changed substantively over the
      decade 1992-2002; there was a shift from intentional injuries to transport
      related deaths as the predominant etiology of trauma related deaths. Recognition
      of such injury patterns will direct future injury-prevention efforts and
      coordination of citywide trauma care.

PMID- 17505855
TI  - Impact of mild and moderate intrapulmonary shunting in children with end-stage
      liver disease undergoing liver transplantation.
AB  - AIM: The aim of this study was to evaluate the impact of mild and moderate
      intrapulmonary shunting (IPS) in children with end-stage liver disease (ESLD)
      undergoing liver transplantation. MATERIALS AND METHODS: A total of 73 patients
      (38 male, 35 female; mean age 31.5 +/- 35.2 months, range 6-180 months) with ESLD
      and subsequent liver transplantation were enrolled. Based on contrast
      echocardiography, patients without IPS were assigned to group 1 (n = 57), and
      patients with mild or moderate IPS were assigned to group 2 (n = 17). The
      preoperative age, body weight, O(2) saturation, length of hospital stay, duration
      of mechanical ventilation, postoperative complications, and 1-year survival rate
      were compared between groups. RESULTS: The overall incidence of IPS and 1-year
      survival rate were 23.3% (17/73) and 96% (70/73), respectively. There were
      significant differences between group 1 and group 2 patients regarding age at
      transplant (35.9 vs. 16.6 months, p = 0.002) and body weight (12.6 vs. 8.5 kg, p
      = 0.002). There were no other statistically significant differences between the
      two groups. CONCLUSION: Although children with mild and moderate IPS were younger
      at the time of transplantation and had significantly lower body weight than those
      without IPS, the presence of mild and moderate IPS in children with ESLD did not
      affect the overall outcome of liver transplantation.

PMID- 17505857
TI  - Isolated adrenal mass in patients with a history of cancer: remember
      pheochromocytoma.
AB  - BACKGROUND: In a patient with a history of cancer, an isolated adrenal mass is
      usually thought to be a metastasis. Although a biochemical work-up to rule out
      pheochromocytoma is recommended, some question its practicality. This study was
      undertaken to determine the incidence of functional adrenal lesions in patients
      with a history of cancer and examine predictive factors for the type of lesion.
      METHODS: At a single institution, 33 patients with an isolated adrenal mass and a
      history of cancer underwent surgical treatment. Patients' records were
      retrospectively analyzed for type of adrenal lesion and other diagnostic
      parameters. RESULTS: There were 20 males and 13 females with a mean age of 58+/-2
      years. Of these, 20 (61%) had adrenal metastases, 8 (24%) had pheochromocytomas,
      and 5 (15%) had adrenal adenomas. Usual diagnostic criteria, including presenting
      symptoms, primary tumor, and other demographic characteristics, did not
      consistently predict the pathology of the lesion. CONCLUSIONS: Nearly 1 in 4
      resected adrenal masses in patients with a history of cancer were
      pheochromocytomas. The high incidence of pheochromocytoma in this series supports
      a thorough work-up, irrespective of previous cancer. Therefore, remember one
      thing in patients with an isolated adrenal mass and a history of cancer:
      pheochromocytoma.

PMID- 17505858
TI  - Laparoscopic sentinel node biopsy in cervical cancer using a combined detection:
      5-years experience.
AB  - BACKGROUND: To evaluate the feasibility after 5 years experience of a
      laparoscopic sentinel node (SN) procedure with combined radioisotopic and patent
      blue labeling in patients with cervical cancer. METHODS: Sixty-seven patients
      (median age 48.9 years) with cervical cancer underwent a laparoscopic SN
      procedure using an endoscopic gamma probe, after both radioactive and patent blue
      injections. After the procedure, all the patients underwent complete laparoscopic
      pelvic/para-aortic lymphadenectomy. RESULTS: At least one SN was identified in 57
      patients (85.1%). According to the Stage, the SN identification rate was 91.2% in
      early-stage cervical cancer and 78.5% in locally advanced cervical cancer. The
      mean number of SN was 2.3 per patient (range 1-5). A total of 129 SNs were
      removed. Lymph node metastasis involvement was identified in the 20 SNs (15.5%)
      from 14 patients (24.6%). Nine of the 14 patients had at least one
      macrometastases, three patients presented micrometastases in H&S, and two
      patients presented isolated single cells. Six patients presented a pelvic non-SN
      involvement including two patients whose SNs were uninvolved. The false-negative
      SNs rate was 12.5% (two patients out of 16). Both patients have locally advanced
      cervical cancer. CONCLUSION: This study confirms that laparoscopic SN detection
      with a combination of radiocolloid and patent blue is accurate in patients with
      early cervical cancer to assess pelvic lymph node status.

PMID- 17505859
TI  - Margin and local recurrence after sublobar resection of non-small cell lung
      cancer.
AB  - BACKGROUND: Local recurrence is a major concern after sublobar resection (SR) of
      non-small cell lung cancer (NSCLC). We postulate that a large proportion of local
      recurrence is related to inadequate resection margins. This report analyzes local
      recurrence after SR of stage I NSCLC. Stratification based on distance of the
      tumor (<1 cm vs >or=1 cm) to the staple line was performed. METHODS: We reviewed
      81 NSCLC patients (44 female) who underwent operation over an 89-month period
      (January 1997 to June 2004). Mean forced expiratory volume in one second
      percentiles (FEV1) was 57%. Mean age was 70 (46-86) years. There were 55 wedge
      and 26 segmental resections. There were 41 tumors with a margin <1 cm and 40 with
      a margin >or=1 cm. Local recurrence was defined as recurrence within the
      ipsilateral lung or pulmonary hilum. RESULTS: There were no perioperative deaths.
      Mean follow-up was 20 months. Margin distance significantly impacted local
      recurrence; 6 of 41 patients (14.6%) developed local recurrence in the group with
      margin less than 1 cm versus 3 of 40 patients (7.5%) in the group with margin
      equal to or more than 1 cm (P = .04). Of the 41 patients with margins <1 cm,
      segmentectomy was used in 7 (17%), whereas in the 40 patients with the >or=1 cm
      margins, segmentectomy was used in 19 (47.5%). CONCLUSIONS: Margin is an
      important consideration after SR of NSCLC. Wedge resection is frequently
      associated with margins less than 1 cm and a high risk for locoregional
      recurrence. Segmentectomy appears to be a better choice of SR when this is chosen
      as therapy.

PMID- 17505860
TI  - The ability of existing questionnaires to measure symptom change after
      paracentesis for symptomatic ascites.
AB  - BACKGROUND: Symptomatic malignant ascites is a problem for patients with advanced
      intra-abdominal malignancy. Although the goal of paracentesis, the most common
      therapeutic intervention, is symptom palliation, the best method of assessing
      symptom improvement is unknown. The aim of this study was to assess the ability
      of existing symptom and quality-of-life questionnaires to detect change in
      symptoms after paracentesis. METHODS: Patients with symptomatic ascites completed
      four questionnaires before and 24 hours after paracentesis. These tests were
      Edmonton Symptom Assessment System-Ascites Modification (ESAS:AM), Memorial
      Symptom Assessment Scale-Short Form, European Organization for the Research and
      Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), and the
      EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module (QLQ
      PAN26). Sensitivity, validity, reliability, and responsiveness of the
      questionnaires were evaluated. RESULTS: Sixty-one patients completed the baseline
      and 44 the follow-up questionnaire. Most patients had ovarian (41%) or
      gastrointestinal cancer (25%); Eastern Cooperative Oncology Group performance
      status was 2 (26%) and 3 (49%). Patients reported major symptoms at baseline;
      symptom scores were highest for the clinically recognized symptoms of ascites.
      Most patients (78%) reported that their symptoms improved after paracentesis. All
      questionnaires showed strong sensitivity, validity, and reliability. Subscales
      that included the most distressing symptoms were most responsive; great
      improvement was seen in abdominal bloating (42% to 54%), anorexia (20% to 37%),
      dyspnea (33% to 43%), insomnia (29% to 31%), fatigue (14% to 17%), and mobility
      (25%). The amount of fluid removed (median, 3.5 L; range, .3% to 9.7 L) did not
      correlate with symptom improvement (r = .29, P = -.10). CONCLUSIONS: Paracentesis
      provides symptom relief that can be measured by existing questionnaires. For
      future clinical trials of symptomatic ascites, the QLQ-C30 and the ESAS:AM
      together, or the QLQ-C30 with the addition of the QLQ-PAN26 ascites and abdominal
      pain subscales could be used.

PMID- 17505861
TI  - Tattooing breast cancers treated with neoadjuvant chemotherapy.
AB  - BACKGROUND: In breast carcinomas treated with neoadjuvant chemotherapy,
      intraoperative identification of residual tumors may be difficult. A well
      tolerated, low-diffusion charcoal suspension has been designed to tattoo breast
      tumors. In this study, we investigated whether this tattooing technique is
      efficient for localizing the tumor after treatment with chemotherapy. METHODS: In
      a series of 109 patients with large breast tumors, a 4% or 10% charcoal
      suspension was injected at the time of the initial biopsy before preoperative
      chemotherapy. RESULTS: Tolerance was good. After three or four cycles of
      chemotherapy, 91 patients underwent conservative treatment, and the surgical
      specimen was examined intraoperatively. The charcoal was detected in 94% of the
      cases. The charcoal was seen in the nodule or at the periphery in the surgical
      specimen without any acute inflammatory reaction or diffusion. CONCLUSIONS: On
      the basis of these results, this micronized charcoal suspension at a defined
      granulometry and a concentration of 10% seems to be ideal for tattooing breast
      carcinomas over a period of 3 months in patients in whom neoadjuvant chemotherapy
      is planned.

PMID- 17505863
TI  - Mediastinitis in pediatric cardiac surgery: treatment and cost-effectiveness in a
      low-income country.
AB  - Mediastinitis is a serious postoperative complication following pediatric cardiac
      surgery. The objective of this study is to evaluate the cost-effectiveness of
      surgical treatment for mediastinitis in Guatemala. All children who underwent a
      median sternotomy and developed postoperative mediastinitis between January 2004
      and December 2005 were evaluated. Type of surgical treatment for mediastinitis,
      hospital outcome, and costs were analyzed. Eighteen (3.3%) of the 535 children
      who underwent a median sternotomy developed mediastinitis. Two patients underwent
      debridement of the infected tissues and delayed sternal closure, whereas 16
      patients had debridement, primary chest closure, and continuous antibiotic
      irrigation of the mediastinum. All 11 patients who had the diagnosis of
      mediastinitis within 2 weeks after the operation survived. Three of the 7
      patients (43%) who had delayed diagnosis died (p = 0.0003); all 3 had
      osteomyelitis (p = 0.0007). Primary closure with antibiotic irrigation was
      associated to a lower mortality rate and proved less expensive in comparison to
      delayed sternal closure (p = 0.003) mainly due to the shorter intensive care
      requirement. Debridement followed by primary closure of the chest and continuous
      antibiotic irrigation of the mediastinum seems to be a feasible and less
      expensive method to treat selected cases of postoperative mediastinitis in
      children.

PMID- 17505864
TI  - Parental factors impacting the enrollment of children in cardiac critical care
      clinical trials.
AB  - Clinical trials are abundant in adult cardiovascular medicine; however, they are
      rare in pediatric cardiology. Pediatric cardiac trial design may be impacted by
      the heterogeneous nature of the underlying cardiac defects, as well as by a
      strong emotional response from parents whose child will undergo a surgical
      intervention. The purpose of this study was to assess factors that may have an
      impact on parents considering enrollment of their child in a clinical trial at
      the time of surgical intervention. A voluntary, self-administered questionnaire
      (14 questions) was provided to parents of children 16 years of age or younger
      during the preadmission testing period. Demographic and procedure-related
      variables were collected for each patient. A total of 119 surveys were analyzed
      over a 1.5-year period. Only 8% of the parents had their child participate in a
      clinical trial in the past. Fifty-six percent of the parents preferred that their
      child's cardiologist or surgeon explain clinical trial details, with 23%
      preferring the principal investigator and 3% preferring the research coordinator.
      Fifty percent of the parents were favorably disposed to participate in a clinical
      trial if the drug or device was currently used by their child's doctor, and 19%
      were encouraged to participate if the drug or device was approved for use in
      adults. The majority of parents (64%) preferred to be asked about participating
      in a trial within 1 month prior to the planned procedure, and 40% preferred to
      discuss trial details at a remote time in an outpatient location. Sixty-three
      percent of parents believed that most of the medications currently used in
      children were already approved by the Food and Drug Administration. Most parents
      (91%) believed that clinical trials conducted in children will help improve
      pediatric health care; 74% believed that their child may receive potential
      benefit from enrolling in a trial. Finally, 43% believed that funding for trials
      should come from government and health care agencies, as opposed to
      pharmaceutical companies (24%). This survey reveals the importance of the
      attending physician and timing in educating parents regarding a cardiac critical
      care clinical trial. These data may impact the design and successful conduct of
      future trials.

PMID- 17505865
TI  - Unusual atrial septal anatomy resulting in an interatrial chamber: the true
      triatrial heart?
AB  - We report two patients who were found to have nearly identical, very peculiar
      atrial septal anatomy. The septum actually consisted of two distinct septa with
      discrete defects creating an interatrial chamber. The orifice from the left
      atrium was unrestrictive, but the orifice to the right atrium was restrictive.
      Overall, there was net left-to-right shunting. This finding represents a clinical
      dilemma: Left untreated, the interatrial chamber might be a nidus for thrombus
      formation, but attempting device closure might result in incomplete obliteration
      of the chamber, also resulting in potential locus for clot formation. Clot
      formation might lead to systemic embolization. Angiographic findings are
      correlated with echocardiographic findings. Embryology and treatment options are
      considered.

PMID- 17505866
TI  - Left main coronary occlusion from Takayasu arteritis in an 8-year-old child.
AB  - Takayasu's arteritis (TA) is a chronic systemic inflammatory disease that usually
      affects the aorta and its primary branches and occasionally the coronary
      arteries. We report the case of an 8-year-old girl who was presented with chest
      pain and was referred to our institution with the presumptive diagnosis of
      pneumonia and sepsis. Ultimately, the patient's chest pain was attributed to
      myocardial infarction secondary to coronary occlusion from TA. She underwent a
      successful stenting of the left main coronary artery with sirolimus-eluting
      stent. In a review of the literature, we discuss the demographic profile,
      clinical and radiographic findings, and available therapeutic options.

PMID- 17505867
TI  - Which diaphragm is lower and why?

PMID- 17505868
TI  - Medical imaging informatics: how it improves radiology practice today.

PMID- 17505869
TI  - Effect of automated image registration on radiologist interpretation.
AB  - In this study, we present preliminary data on the effect of automated 3D image
      alignment on the time to arrive at a decision about an imaging finding, the
      agreement of multiple of multiple observers, the prevalence of comparison
      examinations, and technical success rates for the image alignment algorithm. We
      found that automated image alignment reduced the average time to make a decision
      by 25% for cases where the structures are rigid, and when the scanning protocol
      is similar. For cases where these are not true, there is little or no benefit. In
      our practice, 54% of cases had prior examinations that could be automatically
      aligned. The overall benefit seen in our department for highly similar exams
      might be 20% for neuro and 10% for body; the benefit seen in other practices is
      likely to vary based on scanning practices and prevalence of prior examinations.

PMID- 17505870
TI  - PDA-phone-based instant transmission of radiological images over a CDMA network
      by combining the PACS screen with a Bluetooth-interfaced local wireless link.
AB  - Remote teleconsultation by specialists is important for timely, correct, and
      specialized emergency surgical and medical decision making. In this paper, we
      designed a new personal digital assistant (PDA)-phone-based emergency
      teleradiology system by combining cellular communication with Bluetooth
      interfaced local wireless links. The mobility and portability resulting from the
      use of PDAs and wireless communication can provide a more effective means of
      emergency teleconsultation without requiring the user to be limited to a fixed
      location. Moreover, it enables synchronized radiological image sharing between
      the attending physician in the emergency room and the remote specialist on
      picture archiving and communication system terminals without distorted image
      acquisition. To enable rapid and fine-quality radiological image transmission
      over a cellular network in a secure manner, progressive compression and security
      mechanisms have been incorporated. The proposed system is tested over a code
      division Multiple Access 1x-Evolution Data-Only network to evaluate the
      performance and to demonstrate the feasibility of this system in a real-world
      setting.

PMID- 17505871
TI  - Partial volume compensated reconstruction of three-dimensional mass shapes in
      mammographic images.
AB  - Accurately reconstructing the three-dimensional mass shapes in mammographic
      images is important for classifying the abnormality into malignant or benign. In
      this paper, a partial volume compensated reconstruction technique for mass shapes
      is presented. The two-dimensional shapes of the masses are first automatically
      segmented using a region growing approach. The 3D mass shapes are then
      iteratively refined according to an algebraic reconstruction technique. Partial
      volume estimation is applied on the boundary to get a smoother 3D shape.
      Evaluation results show that the proposed algorithm improves the accuracy of the
      mass reconstruction.

PMID- 17505872
TI  - Incorporation of a Laguerre-Gauss channelized Hotelling observer for false
      positive reduction in a mammographic mass CAD system.
AB  - Previously, we developed a simple Laguerre-Gauss (LG) channelized Hotelling
      observer (CHO) for incorporation into our mass computer-aided detection (CAD)
      system. This LG-CHO was trained using initial detection suspicious region data
      and was empirically optimized for free parameters. For the study presented in
      this paper, we wish to create a more optimal mass detection observer based on a
      novel combination of LG channels. A large set of LG channels with differing free
      parameters was created. Each of these channels was applied to the suspicious
      regions, and an output test statistic was determined. A stepwise feature
      selection algorithm was used to determine which LG channels would combine best to
      detect masses. These channels were combined using a HO to create a single
      template for the mass CAD system. Results from free-response receiver operating
      characteristic curves demonstrated that the incorporation of the novel LG-CHO
      into the CAD system slightly improved performance in high-sensitivity regions.

PMID- 17505873
TI  - A new method for calculating net reproductive rate from graph reduction with
      applications to the control of invasive species.
AB  - Matrix models are widely used for demographic analysis of age and stage
      structured biological populations. Dynamic properties of the model can be
      summarized by the net reproductive rate R (0). In this paper, we introduce a new
      method to calculate and analyze the net reproductive rate directly from the life
      cycle graph of the matrix. We show, with examples, how our method of analysis of
      R (0) can be used in the design of strategies for controlling invasive species.

PMID- 17505874
TI  - Alarm pheromone induces immediate-early gene expression and slow behavioral
      response in honey bees.
AB  - Primer and releaser pheromones are molecules used for communication that induce
      species-specific responses. In contrast to primer pheromones, it is not known
      whether the quicker-acting releaser pheromones can affect brain gene expression.
      We show here that isopentyl acetate (IPA), a releaser pheromone that communicates
      alarm in honey bees, not only provokes a quick defensive response but also
      influences behavior for a longer period of time and affects brain gene
      expression. Exposure to IPA affected behavioral responsiveness to subsequent
      exposures to IPA and induced the expression of the immediate early gene and
      transcription factor c-Jun in the antennal lobes. Our findings blur the long
      standing distinction between primer and releaser pheromone and highlight the
      pervasiveness of environmental regulation of brain gene expression.

PMID- 17505875
TI  - Fluorescence quenching studies of conformational changes induced by cAMP and DNA
      binding to heterodimer of cyclic AMP receptor protein from Escherichia coli.
AB  - In Escherichia coli, cyclic AMP receptor protein (CRP) is known to regulate the
      transcription of about 100 genes. The signal to activate CRP is the binding of
      cyclic AMP. In this study the fluorescence quenching measurements were used to
      observe conformational changes in the structure of CRP after binding of cAMP and
      DNA. We used the constructed CRP heterodimer, which contains only a single Trp13
      residue localized in the N-terminal domain of one CRP subunit. We propose that
      apo-CRP subunits exist in a solution in one conformational state and it changes
      after the ligand binding. We also suggest that the signal transmission upon
      binding of cAMP is possible not only from the N-terminal domain to C-terminal
      domain but also in the opposite direction after binding of specific DNA sequence,
      both with and without cAMP. Thereby it can influence on the CRP's interaction
      with RNA polymerase and the genes expression.

PMID- 17505876
TI  - ADHD correlates, comorbidity, and impairment in community and treated samples of
      children and adolescents.
AB  - Patterns of correlates, comorbidity and impairment associated with attention
      deficit hyperactivity disorder (ADHD) in children and youth were examined in
      representative samples from the community and from treatment facilities serving
      medically indigent youth in Puerto Rico. Information from caretakers and youths
      was obtained using the Diagnostic Interview Schedule for Children, (version IV),
      measures of global impairment, and a battery of potential correlates. In the
      community (N = 1,896) and the treated samples (N = 763), 7.5 and 26.2% of the
      children, respectively, met criteria for DSM-IV ADHD in the previous year.
      Although the prevalence rates and degree of impairment differed, the general
      patterns of correlates, comorbidity and impairment were similar in both
      populations. The exceptions were associated with conduct disorder, anxiety,
      impairment in the ADHD comorbid group, and age factors that appeared to be
      related to selection into treatment.

PMID- 17505877
TI  - Autism, attachment and parenting: a comparison of children with autism spectrum
      disorder, mental retardation, language disorder, and non-clinical children.
AB  - Children with Autism Spectrum Disorder (ASD) have severe and pervasive
      impairments in the development of social interaction, which may affect the
      attachment relationship with their parents and may have an impact on parenting.
      In the current investigation 89 families with young children (mean age 26.5
      months) were involved, who were diagnosed as ASD, mentally retarded (MR), or
      language delayed (LD), or part of a non-clinical comparison group. Attachment
      security was observed with the Brief Attachment Screening Questionnaire, and
      several parental self-report questionnaires assessed the parenting style,
      parental efficacy, parental experiences of daily hassles, social support, and
      psychological problems. Children with ASD were rated as less secure compared to
      the other clinical and normal comparison groups. Parents of non-clinical children
      reported higher levels of authoritative parenting than parents in the ASD group
      and in the total clinical group, and they also received less social support.
      Parents of children with ASD coped remarkably well with the challenges of raising
      a child with ASD.

PMID- 17505878
TI  - Environmental contributions to adolescent delinquency: a fresh look at the shared
      environment.
AB  - Few genetically-informative studies have attempted to explicitly identify the
      shared environmental (i.e., those environmental influences that contribute to
      sibling similarity) factors now known to contribute to adolescent delinquency.
      The current study therefore examined whether the parent-child relationship served
      as one source of these shared environmental influences. Participants were 610
      adoptive and biological families from the Sibling Interaction and Behavior Study
      (SIBS). Parents and adolescents reported on their parent-child conflict and
      parental involvement with child, and adolescents reported on their own delinquent
      behaviors. We employed structural equation modeling and supplementary multilevel
      modeling, finding consistent evidence that the association between delinquency
      and the parent-child relationship is at least partially shared environmental in
      origin. Such findings provide an important extension of previous twin studies, as
      they suggest that passive genotype-environment correlations do not explain
      earlier findings of shared environmental influences on this association.

PMID- 17505880
TI  - G:C > A:T mutations and potential epigenetic regulation of p53 in breast cancer.
AB  - Analysis of germline p53 mutations in breast cancer reveals that the Li-Fraumeni
      and Li-Fraumeni-like syndromes are mostly related to the loss of initiation codon
      133 of regulatory TP53 isoforms (Delta133p53). In eight codons of exons 5-8
      (including 133), mutations are frequent in Li-Fraumeni-related, but scarce in
      sporadic breast cancer, while in six more codons they are frequent both in
      familial and sporadic breast cancers. At the proximity of these codons, we
      observed in somatic mutation databases, 16 codons (minihotspots mostly in exons
      7, 8) which undergo frequent G:C > A:T transitions (non-CpG) in all sporadic
      cancers. In addition, in sporadic breast cancer we observed 35 adjacent codons in
      which the following types of mutation are observed: frequent G:C > A:T
      transitions at CCs/GGs, frequent silent mutations in exons 5,6 and suppressed
      nonsense mutations (5 codons, few records). Non-CpG G:C > A:T transitions in the
      35 codons are rare in familial cancers (p53, BRCA1, or BRCA2-related), but
      frequent in sporadic cancers in organs where Li-Fraumeni-related carcinogenesis
      is common e.g. adrenal cortex, soft tissues. These data are in support of the
      following tissue-specific processes: in sporadic breast cancer (sarcomas etc.),
      loss of methylation sites (in 35 codons mostly next to codon 133), might lead to
      loss of silencing of TP53 isoforms which are suppressed in these tissues. On the
      contrary, "spreading" of cytosine methylation (asymmetric) in a G:C-rich region
      next to common hotspots (codons 238-252 in minihotspots) and mutagenesis probably
      destabilizes all tissues. Frequent C > T activation at non-CpG is also observed
      in prostate sporadic cancer, which similarly to breast, undergoes age-related
      crisis. The above data reveal that tissue-specific epigenetic regulatory
      mechanisms might be involved in p53 instability.

PMID- 17505881
TI  - Erythrocyte surface sialic acid levels of clinically healthy mongrel and exotic
      (alsatian and terrier) breeds of dogs.
AB  - The erythrocyte surface sialic acid concentration of clinically healthy mongrel
      and exotic (Alsatian i.e. German shepherd and Terrier) breeds of dogs was
      analyzed in order to determine their role in the genetic resistance of these
      breeds of dogs to diseases that cause anaemia. The mean erythrocyte surface
      sialic acid (ESA) concentration was 57.08 +/- 1.67, 34.50 +/- 2.30 and 20.20 +/-
      3.54 mg/dl for Mongrel, Alsatian (German shepherd) and Terrier breeds of dogs,
      respectively, on acid hydrolysis. The mean values of ESA obtained following
      enzymic hydrolysis of haemoglobin-free erythrocyte membranes using Clostridium
      chauvoei (Jakari strain) sialidase were 49.08 +/- 0.41, 30.97 +/- 1.82 and 18.64
      +/- 0.75 mg/dl for Mongrel, Alsatian (German shepherd) and Terrier dogs
      respectively. When Trypanosoma vivax sialidase was used the ESA values obtained
      were 50.81 +/- 0.37, 41.70 +/- 0.94 and 19.65 + 0.65 mg/dl for Mongrel, Alsatian
      (German shepherd) and Terrier breeds of dogs respectively. This represents a
      statistically significant difference (P < 0.001) between the mean ESA
      concentration of all the breeds of dogs investigated in this study. The higher
      mean ESA concentration in Mongrel dogs, compared to the exotic breeds may be
      responsible for their resistance to disease conditions, whose aetiologic agents
      produce neuraminidase and also cause anaemia.

PMID- 17505882
TI  - Autonomous microfluidic multi-channel chip for real-time PCR with integrated
      liquid handling.
AB  - We report on a novel, polymer-based, multi-channel device for polymerase chain
      reaction that combines, for the first time, rapid sample processing in less than
      5 min with high throughput at low costs. This is achieved by sample shuttling,
      during which submicroliter sample plugs (approximately 100 nl) are oscillated
      rapidly over three constant-temperature zones by pneumatic actuation with
      integrated system. The accuracy and the speed of the liquid handling have been
      significantly increased, while the design of the device can be kept very simple
      and allows for mass production using conventional low-cost polymer fabrication
      processes. Massive parallelization can lead to a throughput up to 100 samples in
      10 min including the preparation time. The amplification can be optically
      monitored by means of online fluorescence detection. Successful real-time PCR and
      the determination of the threshold cycle, Ct, using the developed device were
      demonstrated with plasmid DNA in a fluorescent real-time format.

PMID- 17505883
TI  - Reconfigurable microfluidic integration of a dual-beam laser trap with biomedical
      applications.
AB  - A dual-beam fiber laser trap, termed the optical stretcher when used to deform
      objects, has been combined with a capillary-based microfluidic system in order to
      serially trap and deform biological cells. The design allows for control over the
      size and position of the trap relative to the flow channel. Data is recorded
      using video phase contrast microscopy and is subsequently analyzed using a custom
      edge fitting routine. This setup has been regularly used with measuring rates of
      50-100 cells/h. One such experiment is presented to compare the distribution of
      deformability found within a normal epithelial cell line to that of a cancerous
      one. In general, this microfluidic optical stretcher can be used for the
      characterization of cells by their viscoelastic signature. Possible applications
      include the cytological diagnosis of cancer and the gentle and marker-free
      sorting of stem cells from heterogeneous populations for therapeutic cell-based
      approaches in regenerative medicine.

PMID- 17505884
TI  - A simple device using magnetic transportation for droplet-based PCR.
AB  - The Polymerase chain reaction (PCR) was successfully and rapidly performed in a
      simple reaction device devoid of channels, pumps, valves, or other control
      elements used in conventional lab-on-a-chip technology. The basic concept of this
      device is the transportation of aqueous droplets containing hydrophilic magnetic
      beads in a flat-bottomed, tray-type reactor filled with silicone oil. The whole
      droplets sink to the bottom of the reactor because their specific gravity is
      greater than that of the silicone oil used here. The droplets follow the movement
      of a magnet located underneath the reactor. The notable advantage of the droplet
      based PCR is the ability to switch rapidly the proposed reaction temperature by
      moving the droplets to the required temperature zones in the temperature
      gradient. The droplet-based reciprocative thermal cycling was performed by moving
      the droplets composed of PCR reaction mixture to the designated temperature zones
      on a linear temperature gradient from 50 degrees C to 94 degrees C generated on
      the flat bottom plate of the tray reactor. Using human-derived DNA containing the
      mitochondria genes as the amplification targets, the droplet-based PCR with
      magnetic reciprocative thermal cycling successfully provided the five PCR
      products ranging from 126 to 1,219 bp in 11 min with 30 cycles. More remarkably,
      the human genomic gene amplification targeting glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) gene was accomplished rapidly in 3.6 min with 40 cycles.

PMID- 17505885
TI  - Integrated siphon-based metering and sedimentation of whole blood on a
      hydrophilic lab-on-a-disk.
AB  - In this paper, we present a novel and fully integrated centrifugal microfluidic
      "lab-on-a-disk" for rapid colorimetric assays in human whole blood. All essential
      steps comprising blood sampling, metering, plasma extraction and the final
      optical detection are conducted within t=150 s in passive, globally hydrophilized
      structures which obviate the need for intricate local hydrophobic surface
      patterning. Our technology features a plasma extraction structure (V=500 nL,
      CV<5%) where the purified plasma (cRBC<0.11%) is centrifugally separated, metered
      by an overflow and subsequently extracted by a siphon-based principle through a
      hydrophilic extraction channel into the detection chamber.

PMID- 17505886
TI  - Peristaltic piezoelectric micropump system for biomedical applications.
AB  - This study presents a peristaltic piezoelectric micropump system to transport
      deionized water and whole blood, and deliver phosphated buffered saline (PBS)
      into the vein of a rat, thus simulating insulin injections for diabetes. The
      proposed system comprises a micropump, a 12 V battery, an ATmega 8535
      microprocessor, a 12-180 V DC-to-DC converter based on transformerless
      technology, three differential amplifiers, an IC 7805, a phase controller, an A/D
      converter, a keyboard and an LCD module. The system can generate step-function
      signals of the 3-, 4-, and 6-phase actuation sequences with voltages of up to 228
      Vpp (+/-114 V) and frequencies ranging from 10 Hz to 100 kHz, as the inputs for
      the pump. It is portable and programmable with a package size of 22x12.8x9 cm.
      Additionally, a protocol of the PEOU (N-(triethosilylpropyl)-O-polyethylene oxide
      urethane) coating is developed to form a self-assembly monolayer, thus increasing
      the hemocompatibility of the micropump, and keeping blood flowing smoothly
      through the micropump without blocking. This study performs the circuit testing
      and fluid pumping, and reveals the effects of actuation sequences and liquid on
      pump performance. The flow rates for pumping DI water and whole blood are 16.6
      121.6 microl/min and 8.6-50.2 microl/min, respectively when the voltages are
      changed from 80 Vpp (+/-40 V) to 140Vpp (+/-70 V). And the maximum backpressures
      are 3.2 and 1.8 kPa for DI water and whole blood at 150 V(pp) (+/-75 V),
      respectively. The mean artery pressure (MAP) and heart rates of the rate are 63
      69 mmHg and 266-279 beats/min, respectively, throughout the injection process,
      indicating an insignificant change in physiological reactions of rats.

PMID- 17505887
TI  - Matrigel coated polydimethylsiloxane based microfluidic devices for studying
      metastatic and non-metastatic cancer cell invasion and migration.
AB  - Three-dimensional (3-D) extracellular matrices (ECM) allow complex biochemical
      and biophysical interactions between cells and matrices. Unlike 2-D systems, 3-D
      models provide a better representation of the micro and local environments in
      living tissues for facilitating the physiological study of cell migration. Here,
      we report a microfluidic device based on polydimethylsiloxane (PDMS) for
      monitoring 3-D cell migration across ECM-coated microgaps with real-time light
      microscopy. We tracked the migration of the invasive MDA-MB-231 (mammary
      carcinoma) cells and mapped out their migration paths. It enabled us to quantify
      the percentage of migrated cells as well as migration information of individual
      cells. This wide spectrum of data acquisition is vital for elucidating the
      migration capabilities of different type of cells and to understand the basic
      mechanism involved in cancer metastasis.

PMID- 17505888
TI  - Membrane-activated microfluidic rotary devices for pumping and mixing.
AB  - Microfluidic devices are operated at a low-Reynolds-number flow regime such that
      the transportation and mixing of fluids are naturally challenging. There is still
      a great need to integrate fluid control systems such as pumps, valves and mixers
      with other functional microfluidic devices to form a micro-total-analysis-system.
      This study presents a new pneumatic microfluidic rotary device capable of
      transporting and mixing two different kinds of samples in an annular microchannel
      by using MEMS (Micro-electro-mechanical-systems) technology. Pumping and mixing
      can be achieved using a single device with different operation modes. The
      micropump has four membranes with an annular layout and is compact in size. The
      new device has a maximum pumping rate of 165.7 microL/min at a driving frequency
      of 17 Hz and an air pressure of 30 psi. Experimental data show that the pumping
      rate increases as higher air pressure and driving frequency are applied. In
      addition, not only can the microfluidic rotary device work as a peristaltic
      pumping device, but it also is an effective mixing device. The performance of the
      micromixer is extensively characterized. Experimental data indicate that a mixing
      index as high as 96.3% can be achieved. The developed microfluidic rotary device
      can be easily integrated with other microfluidic devices due to its simple and
      reliable PDMS fabrication process. The development of the microfluidic rotary
      device can be promising for micro-total-analysis-systems.

PMID- 17505890
TI  - Chemical and colloidal analyses of natural seep water collected from the
      exploratory studies facility inside Yucca Mountain, Nevada, USA.
AB  - Yucca Mountain is being considered as a geological repository for the USA's spent
      nuclear fuel and high-level nuclear waste. Numerous groundwater seeps appeared
      during March 2005 within the exploratory studies facility (ESF), a tunnel
      excavated in the mountain. Because of the relevance to radionuclide transport and
      unsaturated zone-modeling studies, we analyzed the seep samples for major anions
      and cations, rare earth elements, and colloids. Major ion species and elemental
      concentrations in seep samples reflect interaction of the water with the volcanic
      rock and secondary calcites. Elemental fractograms from flow-injection field-flow
      fractionation ICP-MS scans detected Br, Ca, Cl, Cu, Fe, I, Mg, Si, Sr, W, and U
      at void fractions, suggesting they may be present in the form of dissolved
      anions. Colloids approximately 10 nm in hydrodynamic diameter, possibly calcite,
      were also present in the seepage samples. Geochemical calculations indicate,
      however, these may be an artifact (not present in the groundwater) which arose
      because of loss of CO2 during sample collection and storage.

PMID- 17505892
TI  - Organically modified low-grade kaolin as a secondary containment material for
      underground storage tanks.
AB  - Batch scale reactions were conducted to evaluate the efficacy of modified low
      grade kaolin for the treatment of petroleum contaminants. Low-grade kaolin, which
      has been unvalued as material in the mining process because of its low quality
      for commercial products, was modified with HDTMA (hexadecyl-trimethylammonium),
      and its efficiency was compared with that of HDTMA-modified bentonite, which is
      used as a secondary containment barrier for underground storage tanks. The
      sorption capacity and hydraulic conductivity of both the HDTMA-modified bentonite
      and low-grade kaolin were investigated and showed distribution coefficients in
      the sorption of benzene, toluene, ethylbenzene and xylene ranging between 45.7
      and 583.7 and 57.0 and 525.1, respectively. The hydraulic conductivities were
      2.53 x 10(-8) and 5.62 x 10(-8) cm/s for the HDTMA-modified bentonite and low
      grade kaolin, respectively. These results suggest that HDTMA-modified low-grade
      kaolin could be used as a hydraulic barrier against advection migration of
      petroleum contaminants. Simulation of the one-dimensional transport of benzene
      through a liner made of either one of the compounds was also performed. These
      results also showed that HDTMA-modified kaolin more effectively retards the
      transport of benzene.

PMID- 17505893
TI  - Swelling related to ettringite crystal formation in chromite ore processing
      residue.
AB  - Several million tons of Chromite Ore Processing Residue (COPR) were deposited at
      two sites in New Jersey and Maryland, USA, and over time they exhibited extensive
      heaving phenomena. Ettringite, a needle-shaped mineral and an expansive mineral
      commonly recognized in the literature concerning cement- and soil, has been
      identified extensively in numerous COPR samples collected from these sites. It
      was therefore believed that ettringite formation and its crystal growth are
      strongly associated with COPR heaving. We investigated the correlation between
      ettringite and the heaving phenomena in COPR materials that contained no initial
      ettringite. Two identical COPR samples were exposed to a 4% w/w sulfate solution
      (25 degrees C, 50 degrees C) in a confined swell test apparatus. Both swell test
      samples were analyzed by means of X-ray powder diffraction. The peak intensities
      of newly formed ettringite were more pronounced in the sample tested at 50
      degrees C, and swell development was only observed in this sample. Scanning
      electron microscopy analyses revealed well-crystallized ettringite needles
      exceeding 40 microm in length for this sample, while ettringite crystals less
      than 15 microm in length formed in the sample tested at 25 degrees C. Therefore,
      the results suggest that the quantity of ettringite and the extent of
      crystallization play a key role in the heave of COPR.

PMID- 17505894
TI  - Enhancement of As(V) adsorption onto activated sludge by methylation treatment.
AB  - Biosorption properties of arsenate [As(V)] onto activated sludge were
      investigated in batch systems. The adsorption of As(V) onto sludge increased from
      23 to 266 microg/g dry weight through the methylation of the activated sludge.
      This increase resulted from neutralization of carboxylic groups via the
      methylation process. The pH effect of As(V) uptake was also investigated and
      As(V) adsorption by methylated sludge decreased significantly at high pH (pH >
      11) due to competition between As(V) and OH(-) ions for binding sites distributed
      on sludge surfaces. In contrast, low pH favored As(V) adsorption by methylated
      sludge because of the elevated quantities of positively charged functional
      groups. The results suggest that methylated activated sludge may provide
      promising applications for the simultaneous removal and separation of As(V) from
      aqueous effluents.

PMID- 17505895
TI  - An assessment of sampling, preservation, and analytical procedures for arsenic
      speciation in potentially contaminated waters.
AB  - This study was undertaken to ascertain optimal methods of sampling, preserving,
      separating, and analyzing arsenic species in potentially contaminated waters.
      Arsenic species are readily transformed in nature by slight changes in
      conditions. Each species has a different toxicity and mobility. The conventional
      field sampling method using filters of 0.45 microm in size could overestimate the
      dissolved arsenic concentrations, as passing suspended particles that can act as
      a sink or source of arsenic depending on the site condition. For arsenic species
      in neutral pH and iron-poor waters, the precipitation can be stable for up to 3
      days without any treatment, but for longer periods, a preservative, such as
      phosphoric acid, is required. Also, the analytical procedure must be selected
      carefully because the levels and hydride generation efficiencies of arsenic in
      different species can vary, even for the same amount of arsenic. For arsenic
      speciation in samples that also include organic species, a hybrid high
      performance liquid chromatography (HPLC) column and inductively coupled plasma
      mass spectrometry (ICP-MS) gave the best resolution and lowest detection limits.
      However, the procedure using a solid phase extraction (SPE) cartridge can be used
      economically and conveniently for analyzing samples containing only inorganic
      arsenic species, such as groundwater, especially that related to mine activity.

PMID- 17505896
TI  - New times, new needs; e-epidemiology.
AB  - The successful and systematic collection of demographic and lifestyle data is
      central in the process of any epidemiological study. The traditionally used
      methods such as face-to-face and telephone interviews as well as paper
      questionnaires are increasingly failing to produce good qualitative results
      within financially feasible limits. Tools that are better suited for the present
      dynamic populations are needed and the Internet presents a powerful alternative
      for the collection of data with several intrinsic features still unexplored.

PMID- 17505897
TI  - Binding property of avian skeletal muscle ryanodine receptor isoforms with
      dihydropyridine receptor and calmodulin.
AB  - Ca(2+) release during excitation-contraction coupling in avian skeletal muscle is
      controlled by two ryanodine receptor isoforms, alphaRYR and betaRYR. Two other
      proteins, dihydropyridine receptor (DHPR) and calmodulin (CaM), have been shown
      to play important roles in regulating the RYR channel activity. In the current
      study, we measured the protein contents of DHPR and RYR in turkey skeletal muscle
      and obtained a ratio of 1:1 between DHPR and alphaRYR which suggests that only a
      subpopulation of alphaRYR is interacting with DHPR. Two CaM derivatives, the
      photoactivable crosslinking probe [(125)I]-Bz-CaM and metabolically labeled probe
      [(35)S]CaM, were used to study the interaction between CaM and RYR isoforms in
      turkey skeletal muscle. The alphaRYR and betaRYR displayed a marked difference in
      their CaM binding behavior. At a Ca(2+) concentration of 200 microM, CaM bound to
      both isoforms at a ratio of one CaM molecule per one RYR subunit. At a Ca(2+)
      concentration of <10 nM, CaM bound primarily to alphaRYR and the binding affinity
      was significantly lower than that at micromolar level of Ca(2+) concentration.
      Cloning and sequencing of putative CaM binding sites in alphaRYR and betaRYR
      suggests that differences in primary structures of the CaM binding sites of each
      RYR isoform may contribute to the differential CaM binding behavior of alphaRYR
      and betaRYR.

PMID- 17505898
TI  - Contribution to biomonitoring of some trace metals by deciduous tree leaves in
      urban areas.
AB  - Leaves of the deciduous tree species, horse chestnut (Aesculus hippocastanum L.)
      and Turkish hazel (Corylus colurna L.) were used as accumulative biomonitors of
      trace metal pollution in the urban area of Belgrade. Using differential pulse
      anodic stripping voltametry, trace metal concentrations (Pb, Cu, Zn, Cd) were
      determined at the single leaf level (ten leaves per species, per month), during
      two successive years with markedly different atmospheric level of trace metals.
      Increased trace metal concentrations in the leaves of A. hippocastanum reflected
      elevated atmospheric trace metal pollution, whereas C. colurna L. did not respond
      accordingly. The contents of Pb and Zn in soil over the same period also followed
      this trend. Anatomical analyses, in young as well as in old leaves of both
      species, indicated typical foliar injuries of plants exposed to stressful air
      conditions. Water relations that correspond to leaf age may have contributed to
      the considerable trace metal accumulation in leaves.

PMID- 17505899
TI  - Testing differences in methods of preparing moss samples.
AB  - Various methods are currently used to prepare moss samples prior to their
      analysis in biomonitoring surveys. To date there has been no investigation of
      whether different results are obtained by using different preparation techniques.
      We therefore selected three preparation procedures (freezing, drying and
      acclimatization), currently applied in the European Moss Survey and other
      studies, to test whether significantly different concentrations of Al, As, Cd,
      Cr, Cu, Fe, Hg, K, Ni, Pb, Se, V and Zn are obtained. In addition, we considered
      the effect that the degree and type of contamination of the sampling sites and
      the different times of the year may have on the results. We found significant
      differences in the concentrations of all elements in the moss samples subjected
      to the different procedures and recommend standardization of the methods of
      sample preparation for valid comparison of the results. We further recommend that
      the samples are picked over directly in the field, to remove adhering material,
      and then cleaned prior to analysis.

PMID- 17505900
TI  - Measurement of particle concentrations in a dental office.
AB  - Particles in a dental office can be generated by a number of instruments, such as
      air-turbine handpieces, low-speed handpieces, ultrasonic scalers, bicarbonate
      polishers, polishing cups, as well as drilling and air sprays inside the oral
      cavity. This study examined the generation of particles during dental drilling
      and measured particle size, mass, and trace elements. The air sampling techniques
      included both continuous and integrated methods. The following particle
      continuous measurements were taken every minute: (1) size-selective particle
      number concentration (Climet); (2) total particle number concentration (PTRAK),
      and; (3) particle mass concentration (DustTrak). Integrated particle samples were
      collected for about 5 h on each of five sampling days, using a PM(2.5) sampler
      (ChemComb) for elemental/organic carbon analysis, and a PM(10) sampler (Harvard
      Impactor) for mass and elemental analyses. There was strong evidence that these
      procedures result in particle concentrations above background. The dental
      procedures produced number concentrations of relatively small particles (<0.5
      microm) that were much higher than concentrations produced for the relatively
      larger particles (>0.5 microm). Also, these dental procedures caused significant
      elevation above background of certain trace elements (measured by X-ray
      fluorescence) but did not cause any elevation of elemental carbon (measured by
      thermal optical reflectance). Dental drilling procedures aerosolize saliva and
      products of drilling, producing particles small enough to penetrate deep into the
      lungs. The potential health impacts of the exposure of dental personnel to such
      particles need to be evaluated. Increased ventilation and personal breathing
      protection could be used to minimize harmful effects.

PMID- 17505901
TI  - Integrating sentinel watershed-systems into the monitoring and assessment of
      Minnesota's (USA) waters quality.
AB  - Section 303(d) of the Clean Water Act requires States and Tribes to list waters
      not meeting water quality standards. A total maximum daily load must be prepared
      for waters identified as impaired with respect to water quality standards.
      Historically, the management of pollution in Minnesota has been focused on point
      source regulation. Regulatory effort in Minnesota has improved water quality over
      the last three decades. Non-point source pollution has become the largest driver
      of conventional 303(d) listings in the 21st century. Conventional pollutants,
      i.e., organic, sediment and nutrient imbalances can be identified with poor land
      use management practices. However, the cause and effect relationship can be
      elusive because of natural watershed-system influences that vary with scale.
      Elucidation is complex because the current water quality standards in Minnesota
      were designed to work best with water quality permits to control point sources of
      pollution. This paper presents a sentinel watershed-systems approach (SWSA) to
      the monitoring and assessment of Minnesota waterbodies. SWSA integrates physical,
      chemical, and biological data over space and time using advanced technologies at
      selected small watersheds across Minnesota to potentially improve understanding
      of natural and anthropogenic watershed processes and the management of point and
      non-point sources of pollution. Long-term, state-of-the-art monitoring and
      assessment is needed to advance and improve water quality standards. Advanced
      water quality or ecologically-based standards that integrate physical, chemical,
      and biological numeric criteria offer the potential to better understand, manage,
      protect, and restore Minnesota's waterbodies.

PMID- 17505902
TI  - Concentrations of airborne pollen grains in Sivrihisar (Eskisehir), Turkey.
AB  - Pollen grains in the atmosphere of Sivrihisar were studied for a continuous
      period of 2 years (1 January 2005-31 December 2006) using a Durham sampler.
      During this period, pollen grains belonging to 41 taxa were recorded, 24 of which
      belonged to arboreal plants and 17 to non-arboreal. From these, 23,219 were
      identified in 2005 and 34,154 in 2006. Of the total pollen grains, 90.46% were
      arboreal, 9.43% non-arboreal, and 0.1% unidentifiable. The majority of the
      investigated allergic pollen grains were from Pinaceae, Cupressaceae, Fraxinus
      spp., Cedrus spp., Artemisia spp., Poaceae, Chenopodiaceae/Amaranthaceae, Populus
      spp., Quercus spp., Urticaceae and Asteraceae, respectively. Pollen
      concentrations reached their highest levels in May. This information was then
      established into a calendar form according to the pollens determined in 2005
      2006, in terms of annual, monthly and weekly numbers of taxa fall per cm2. A
      comparison between the results and the meteorological factors revealed a close
      relationship between pollen concentrations in the air and meteorological
      conditions. An increase in pollination was also linked to increasing temperatures
      and the wind. It was therefore concluded that high temperatures and relative
      humidity were also effective in increasing the number of pollens in the air.

PMID- 17505903
TI  - Simulation of arsenic partitioning in tributaries to drinking water resevoirs.
AB  - Arsenic released by bottom sediments was determined by experiments in which the
      sediments were artificially re-suspended using a particle entrainment simulator
      (PES) to simulate river conditions. Sediment cores were collected from various
      tributaries to drinking water reservoirs in Connecticut spiked with arsenic, and
      run in the PES at simulated bed-flow shear stresses from 0.0 to 0.6 N/m(2). Under
      equilibrium conditions, the dissolved fraction of arsenic was found to range from
      8.3 to 22.1 microg/l, which in most cases exceeded EPA Maximum Contaminant Level
      (MCL) of 10 microg/l. Experimental results from these simulations have shown that
      bed-flow shear stress causes an increased concentration of dissolved arsenic,
      most notably at shear stresses of 0.4, 0.5, and 0.6 N/m(2). For the solid phase
      under equilibrium, the concentrations of arsenic ranged between 71 and 275 mg/kg.
      The average concentration of arsenic on the solid phase as well as partitioning
      coefficient values (K (p)) were highest at initial shear stress. This was
      attributed to the higher fraction of colloidal material and finer organic
      particles in the suspended solid mixture. Particles of such nature proved to have
      higher affinity to arsenic. K (p) values were determined from PES data and were
      found to range from 4,687 to 24,090 l/kg. However, on a mass load basis, the
      amount of arsenic found in suspended sediment increased with the increase of
      shear stress. Similarly, the amount of arsenic in the solid phase increased
      significantly for sites with high Volatile Organic Carbon (VOC) content. Because
      of the influence of Total Suspended Solids (TSS) and VOC concentrations on K (p),
      the use of the PES is more appropriate in obtaining K (p) values that would be
      found under real stream conditions when compared to the traditional way of
      measuring K (p) using a jar study technique.

PMID- 17505904
TI  - Analysis of tropospheric ozone concentration on a Western Mediterranean site:
      Castellon (Spain).
AB  - Ozone dynamics in our study area (Castellon, Spain) is both strongly bound to the
      mesoscale circulations that develop under the effect of high insolation
      (especially in summer) and conditioned by the morphological characteristics of
      the Western Mediterranean Basin. In this work we present a preliminary analysis
      of ozone time series on five locations in Castellon for the period 1997-2003. We
      study their temporal and spatial variations at different scales: daily, weekly,
      seasonally and interannually. Because both the O3 concentration and its temporal
      variation depend on the topographic location of the observing station, they can
      show large differences within tens of kilometer. We also contrast the variation
      in the ozone concentration with the variations found for meteorological variables
      such as radiation, temperature, relative humidity and recirculation of the air
      mass. The link between elevated ozone concentrations and high values of the
      recirculation factor (r=0.7-0.9) shown the importance of recirculating flows on
      the local air pollution episodes.

PMID- 17505905
TI  - Assessment of the efficiency and economic viability of various methods of
      treatment of sanitary landfill leachate.
AB  - This study assesses the efficiency of various physico-chemical, biological and
      other tertiary methods for treating leachate. An evaluation study on the
      treatability of the leachate from methane phase bed (MPB) reactor indicated that
      at an optimum hydraulic retention time of 6 days, the efficiency of the reactor
      in terms of biological oxygen demand (BOD) and chemical oxygen demand (COD)
      removal was 91.29 and 82.69%, respectively. Recycling of the treated leachate
      through the municipal solid waste layers in the leachate recycling unit (LRU)
      resulted in a significant increase in the biodegradation of organics present in
      the leachate. Optimum BOD and COD removal efficiencies were achieved at the third
      recycle; additional recycling of the leachate did not produce any significant
      improvement. Physico-chemical treatment of the leachate demonstrated that alum
      and lime (Option 2) were more economical than coagulants lime and MgCO(3). A cost
      analysis of the economics of the various treatments revealed that the alternative
      treatment consisting of a MPB bed followed by a LRU and aerated lagoon is the
      most cost-effective treatment. However, the alternative consisting of a MPB
      followed by the LRU and a soil column, which is slightly more costly, would be
      the most appropriate treatment when adequate land is readily available.

PMID- 17505906
TI  - Leachate from market refuse and biomethanation study.
AB  - The market place is considered to be an important centre of daily life of campus
      community. In India, as in Europe and the USA, other forms of shopping have
      emerged significantly and now predominate, for instance department stores and
      supermarkets. Though, it is suffered from poor waste management, but the place
      could be a potential source for obtaining non-conventional energy. The present
      study examined the quality of market waste management of the Indian Institute of
      Technology Campus along with the feasibility of biogas production from leachate
      generated in the waste. Solid wastes from different storage locations of the
      market place were collected and analyzed. The characteristics of solid wastes
      were found to be degradable in nature. The wastes, composed of 85% of vegetable
      origin, were placed in a container and water was added to to generate leachate.
      The self-purification efficiency of leachate was also studied in the Indian
      environment and compared with research findings in the USA under an identical
      moisture application rate. Leachate characterization was investigated both under
      saturated and submerged conditions. The treatability of leachate was studied in a
      laboratory-scale up-flow anaerobic filter with hollow burnt clay rings as packing
      media. It was observed that 4,000-6,000 mg/l would be the optimum range of inlet
      chemical oxygen demand (COD) concentration for leachate treatment because of the
      inhibitory effect of ammonia, sulphide, volatile fatty acids and toxic metals in
      high concentrations at higher strengths of leachate. The gas production rate was
      found to be at a maximum at 38 degrees C and containing 70-75% methane. From
      experimental data, it was revealed that 83% COD was removed with input COD
      concentration of 5,475 mg/l at 2 days hydraulic retention time with biogas yield
      coefficients of 0.61. The present study also investigated the removal efficiency
      of chloride, ammonia, sulphide and nitrate.

PMID- 17505907
TI  - Exploratory study of suspended sediment concentrations downstream of harvested
      peat bogs.
AB  - Peat bog harvesting is an important industry in many countries, including Canada.
      To harvest peat, bogs are drained and drainage water is evacuated towards
      neighboring rivers, estuaries or coastal waters. High suspended sediment
      concentrations (SSC) were found in the drainage water at one particular site
      during the 2001-2002 spring seasons in New Brunswick (Canada). The main objective
      of this study was to verify this observation at other sites, compare SSC levels
      leaving harvested peat bogs with those leaving an unharvested bog, and to
      determine if high SSC events happen only in Spring or all year round. Suspended
      sediment concentrations were monitored downstream of three harvested peat bogs
      and an unharvested reference bog located in New Brunswick during the ice free
      seasons of 2003-2004. On average, SSC at the harvested sites exceeded 25 mg/l,
      which is the recommended daily maximum concentration, 72% of the time, while the
      same concentration was exceeded 30% of the time at the unharvested sites. SSC
      were found to be significantly higher at harvested sites than at the reference
      sites for all seasons. The highest SSC medians were recorded in the Fall but SSC
      was elevated in all seasons. High SSC levels in receiving waters may be caused by
      field ditching activities and insufficient sediment controls. Findings suggest
      the NB Peat Harvesting 25 mg/l SSC guideline should be reviewed.

PMID- 17505908
TI  - Simulation of nitrogen dynamics in soil using infocrop model.
AB  - Nitrogen is the most widely used fertilizer nutrient, and it is a universally
      deficient nutrient too, which often severely restricts the growth and yield of
      crops. To improve N fertilizer management, soil-plant system models can be
      applied to simulate adequate N supply for both, optimal crop growth and minimal N
      losses. The likely impact of climate change on the cereal production is of
      paramount importance in the planning strategies to meet the future growing needs
      on sustainable grounds. In this scenario models are the effective tools to
      foresee the probable impacts and for choosing appropriate land use options. The
      study reported in this thesis, employs field experiments and use of simulation
      tools to understand the dynamics of soil N balance and relate growth and yield of
      rice under varying nitrogen inputs. The InfoCrop model was used in this study,
      which was calibrated with the historic data sets, and subsequently validated with
      the field experiment conducted at IARI Farm, New Delhi. Simulated results matched
      well with the observed values in terms of growth and yield of rice and seasonal
      nitrogen uptake. The components of soil nitrogen balance differed among varying
      nitrogen level treatments, which was also captured by use of InfoCrop. The model
      was then taken to climate change impact analysis. The results clearly revealed
      that when temperature increased, the soil N losses, like denitrification,
      volatilization, N2O emission increased, whereas grain and biomass yields
      decreased. The further scope of the study is to validate the study in contrasting
      agroenvironments.

PMID- 17505909
TI  - Effects of transanal pelvic plexus stimulation on penile erection: clinical
      implications.
AB  - OBJECTIVE: To determine the ability of transanal pelvic plexus stimulation (TPPS)
      in inducing penile tumescence in patients with non-neurogenic erectile
      dysfunction (ED) and to compare the erection degree with papaverine-induced
      erection. PATIENTS AND METHODS: The cavernous electrical activity (CEA) in 21 men
      with non-neurogenic erectile dysfunction was measured during TPPS by
      electromyography of corpus cavernosum and the erection degree of penis (flaccid,
      semi-rigid, rigid) was noted. The stimulation amplitude was increased from 20 to
      100 mA. All patients also underwent intracavernous papaverine injection and
      further CEA recordings were obtained. RESULTS: Twelve and nine patients were
      diagnosed with vasculogenic (VED) and non-vasculogenic ED (NVED), respectively.
      TPSS led to a penile erectile response in 12 patients (57%), whereas papaverine
      injection caused erection in 16 (76.2%) patients. The mean baseline CEA (16.9 +/-
      9.1 mV) did not change with TPPS, but papaverine significantly decreased the mean
      CEA to 12.3 +/- 4.9 mV (P < 0.001). CEA recordings of 16 (76.2%) patients
      revealed a significant decrease after papaverine injection, however seven (33.3%)
      patients showed significant CEA decrease in response to TPPS. Both TPPS and
      papaverine were observed to have a higher effect in patients with NVED in terms
      of inducing penile erection and decreasing CEA compared to their effects in
      patients with VED. CONCLUSION: TPPS induces penile erection and decreases CEA for
      some extent, but to a lesser degree compared to papaverine. As further
      improvements are achieved in the methodology of TPPS, it may be a valuable method
      in the evaluation patients with erectile dysfunction.

PMID- 17505910
TI  - Chlorophylls, ligands and assembly of light-harvesting complexes in chloroplasts.
AB  - Chlorophyll (Chl) b serves an essential function in accumulation of light
      harvesting complexes (LHCs) in plants. In this article, this role of Chl b is
      explored by considering the properties of Chls and the ligands with which they
      interact in the complexes. The overall properties of the Chls, not only their
      spectral features, are altered as consequences of chemical modifications on the
      periphery of the molecules. Important modifications are introduction of oxygen
      atoms at specific locations and reduction or desaturation of sidechains. These
      modifications influence formation of coordination bonds by which the central Mg
      atom, the Lewis acid, of Chl molecules interacts with amino acid sidechains, as
      the Lewis base, in proteins. Chl a is a versatile Lewis acid and interacts
      principally with imidazole groups but also with sidechain amides and water. The 7
      formyl group on Chl b withdraws electron density toward the periphery of the
      molecule and consequently the positive Mg is less shielded by the molecular
      electron cloud than in Chl a. Chl b thus tends to form electrostatic bonds with
      Lewis bases with a fixed dipole, such as water and, in particular, peptide
      backbone carbonyl groups. The coordination bonds are enhanced by H-bonds between
      the protein and the 7-formyl group. These additional strong interactions with Chl
      b are necessary to achieve assembly of stable LHCs.

PMID- 17505913
TI  - Bilateral renal cell carcinoma development in long-term Fabry disease.

PMID- 17505911
TI  - UV-induced phycobilisome dismantling in the marine picocyanobacterium
      Synechococcus sp. WH8102.
AB  - The marine picocyanobacterium Synechococcus sp. WH8102 was submitted to
      ultraviolet (UV-A and B) radiations and the effects of this stress on reaction
      center II and phycobilisome integrity were studied using a combination of
      biochemical, biophysical and molecular biology techniques. Under the UV
      conditions that were applied (4.3 W m(-2) UV-A and 0.86 W m(-2) UV-B), no
      significant cell mortality and little chlorophyll degradation occurred during the
      5 h time course experiment. However, pulse amplitude modulated (PAM) fluorimetry
      analyses revealed a rapid photoinactivation of reaction centers II. Indeed, a
      dramatic decrease of the D1 protein amount was observed, despite a large and
      rapid increase in the expression level of the psbA gene pool. Our results suggest
      that D1 protein degradation was accompanied (or followed) by the disruption of
      the N-terminal domain of the anchor linker polypeptide LCM, which in turn led to
      the disconnection of the phycobilisome complex from the thylakoid membrane.
      Furthermore, time course analyses of in vivo fluorescence emission spectra
      suggested a partial dismantling of phycobilisome rods. This was confirmed by
      characterization of isolated antenna complexes by SDS-PAGE and immunoblotting
      analyses which allowed us to locate the disruption site of the rods near the
      phycoerythrin I-phycoerythrin II junction. In addition, genes encoding
      phycobilisome components, including alpha-subunits of all phycobiliproteins and
      phycoerythrin linker polypeptides were all down regulated in response to UV
      stress. Phycobilisome alteration could be the consequence of direct UV-induced
      photodamages and/or the result of a protease-mediated process.

PMID- 17505914
TI  - Neonatal screening: from the 'Guthrie age' to the 'genetic age'.
AB  - Newborn screening has 'traditionally' been performed to detect metabolic or
      endocrine diseases that are severe, frequent and treatable, according to criteria
      established in the late 1960s. Technological advances in laboratory testing over
      the past ten years open new possibilities. However, many new problems have to be
      explored before the establishment or expansion of a newborn screening programme.
      The purpose of this paper is to present some of the major problems that screening
      programmes will face in the near future.

PMID- 17505915
TI  - Newborn screening for cystic fibrosis: techniques and strategies.
AB  - Newborn screening for cystic fibrosis has been carried out for over 25 years, and
      clinical and cost benefits have been documented. There is still much variation in
      the methods and strategies adopted. All current screening programmes use a
      measurement of immunoreactive trypsin as a primary screening test, and in most, a
      second tier test involves analysing DNA mutations. The choice of DNA mutations
      depends on the genetic background in the region, and considerations of cost.
      Using DNA analysis as part of a screening procedure has introduced unwanted
      carrier detection, and protocols have now been devised in an attempt to avoid
      this. There are at least seven distinct protocols in use, all of which have
      different advantages and disadvantages, and no method or strategy will suit every
      region. Further careful study of performance and costs of various strategies is
      needed.

PMID- 17505917
TI  - HIV prevention with severely mentally ill men: a randomised controlled trial.
AB  - We conducted a randomised clinical trial to test the efficacy of an enhanced
      version of an intervention previously shown to reduce HIV sexual risk behaviours
      among men with severe mental illness. One-hundred-and-forty-nine subjects aged 18
      59 years were randomly assigned to the experimental or control conditions. Sexual
      risk behaviours were assessed every three months for 12-months. The primary
      analysis compared experimental and control groups with respect to sexual risk
      behaviours with casual partners as measured by the Vaginal Episodes Equivalent
      (VEE) score. Additional analyses included comparison of VEE scores of those men
      sexually active in the three months prior to baseline and the proportion of
      condom-protected sexual acts with casual partners. There were no significant
      differences in sexual risk behaviours with casual partners between experimental
      and control subjects. Additional analyses demonstrated a trend toward sexual risk
      reduction at six months post-intervention (p=0.06) but not at 12 months. These
      results may reflect a lack of efficacy or a true reduction in risk that the trial
      was underpowered to detect at the 0.05-level. If there was a true reduction in
      risk, it was not maintained after the initial six months.

PMID- 17505916
TI  - Several transcription factors regulate COX-2 gene expression in pancreatic beta
      cells.
AB  - Cyclooxygenase-2 (COX-2) expression is associated with many aspects of
      physiological and pathological conditions, including pancreatic beta-cell
      dysfunction. Prostaglandin E2 (PGE2) production, as a consequence of COX-2 gene
      induction, has been reported to impair beta-cell function. The molecular
      mechanisms involved in the regulation of COX-2 gene expression are not fully
      understood. In this report, we used pancreatic beta-cells (RINm5F) to explore the
      potential transcription factors regulating COX-2 promoter activity. Using
      promoter screening method, we selected several transcription factors in our
      study. Through luciferase reporter studies, we found that these factors can
      regulate COX-2 promoter activity in RINm5F cells. Among these factors, cyclic AMP
      response-element binding protein (CREB), Ets family members Ets-1 and Elk-1 can
      positively regulate COX-2 promoter activity. On the contrary, signal transducer
      and activator of transcription 1 (STAT1) plays a negative role on COX-2 promoter.
      Our findings will be helpful for better understanding the transcriptional
      regulation of COX-2 in pancreatic beta-cells. Moreover, these transcriptional
      regulators of COX-2 expression will be potential targets for the prevention of
      beta-cell damage mediated by PGE2.

PMID- 17505918
TI  - Complementary and alternative medicine use decreases adherence to HAART in HIV
      positive women.
AB  - The use of complementary and alternative medicine (CAM) to treat chronic
      illnesses, especially HIV, is becoming increasingly widespread. Given this
      popularity, it is critical to understand how HIV-positive individuals use CAM
      and, more specifically, whether CAM use impacts their adherence to prescribed
      antiretroviral regimens (HAART). The present study examined the relationship
      between CAM use and HAART adherence among HIV+ women. Data were analysed from 366
      HIV-positive, mostly African-American women, aged 18-50 years in Alabama and
      Georgia who were enrolled in an intervention to reduce high-risk sexual
      behaviour. At enrollment data were collected describing use of CAM and HAART use.
      Women were classified as CAM users if they reported taking herbal/natural
      immunity boosters (Chinese herbs, mushrooms, garlic, ginseng or algae) or
      multivitamins, or reported using religious/psychic health or bodywork to treat
      HIV. Women were classified as non-adherent if they reported missing any doses of
      their HAART medication in the 30 days preceding baseline assessment. Logistic
      regressions models, adjusted for potential confounders, were used to investigate
      the relationship between CAM use and HAART adherence. Women using CAM (immunity
      boosters or vitamins), relative to non-CAM users, were 1.69 times more likely to
      report missing HAART doses in the last 30 days (CI: 1.02-2.80; P=.041) even after
      adjusting for age, education, race, religion and income. The findings provide
      preliminary evidence that patients using CAM may be doing so as an alternative to
      traditional medicine as opposed to complementing prescribed HARRT treatment
      regimens. The inconsistent use of HAART is problematic given its association with
      drug resistance. Therefore, health care providers and patients should have
      explicit dialogues about how to effectively integrate CAM practices into
      traditional treatment regimens so that the safety and health of HIV-positive
      patients is not compromised.

PMID- 17505920
TI  - Evaluation of use of cellphones to aid compliance with drug therapy for HIV
      patients.
AB  - Key to the care of people living with HIV is effective data on use of ARVs, their
      responses to the medication and additional needs. An adaptation of cellphone
      technology by Cell-Life provides an easy-to-use data capturing devise for use by
      therapeutic counsellors (home based carers). Individual in-depth interviews were
      conducted with all the counsellors using the technology at two points in time,
      six months apart. The technology was found to be easy to use, especially for
      those who had previously used a cellphone. It eased data collection considerably
      and reduced fears around loosing notes. Improvements in technology between the
      two sets of interviews showed responsiveness from Cell-Life to the users of the
      technology. The patients also responded well to the technology, feeling that it
      improved their treatment. The major concern for home-based carers was the risk of
      crime due to having a cellphone, which led to the therapeutic counsellors
      eventually leaving the cellphones at home when visiting patients and entering the
      data at a later point. While the carers initially felt that the technology was an
      intrusion in their lives they later adapted to it.

PMID- 17505919
TI  - Modeling HIV transmission risk among Mozambicans prior to their initiating highly
      active antiretroviral therapy.
AB  - Understanding sexual behavior and assessing transmission risk among people living
      with HIV-1 is crucial for effective HIV-1 prevention. We describe sexual behavior
      among HIV-positive persons initiating highly active antiretroviral therapy
      (HAART) in Beira, Mozambique. We present a Bernoulli process model (tool
      available online) to estimate the number of sexual partners who would acquire HIV
      1 as a consequence of sexual contact with study participants within the prior
      three months. Baseline data were collected on 350 HAART-naive individuals 18-70
      years of age from October 2004 to February 2005. In the three months prior to
      initiating HAART, 45% (n = 157) of participants had sexual relationships with 191
      partners. Unprotected sex occurred in 70% of partnerships, with evidence
      suggesting unprotected sex was less likely with partners believed to be HIV
      negative. Only 26% of the participants disclosed their serostatus to partners
      with a negative or unknown serostatus. Women were less likely to report
      concurrent relationships than were men (21 versus 66%; OR 0.13; 95%CI: 0.06,
      0.26). Given baseline behaviors, the model estimated 23.2 infections/1,000 HIV
      positive persons per year. The model demonstrated HAART along with syphilis and
      herpes simplex virus type 2 (HSV-2) treatment combined could reduce HIV-1
      transmission by 87%; increasing condom use could reduce HIV-1 transmission by
      67%.

PMID- 17505921
TI  - The impact of HIV-related interventions on HIV risk behavior in a community
      sample of African American crack cocaine users.
AB  - While there are reports of the impact of specific interventions designed to
      reduce HIV drug and sexual risk behaviors, there are few reports of the impact of
      HIV interventions in a community-based sample. We report on baseline data from a
      sample of African American crack smokers who were about to participate in an
      intervention designed to reduce HIV-related risk behaviors. The majority were
      male (80%), single (70%) and homeless (52%). Data indicated that 29% of the
      sample had been in a previous HIV intervention in the past 12 months, the
      majority in a correctional setting or CBO program. There were few systematic
      demographic differences between the two groups. Those who had been in an
      intervention reported using male and female condoms significantly more frequently
      on all measures of condom use, had positive condom use outcome expectations for
      male condoms and higher affective and situational condom-related self-efficacy
      beliefs. These data suggest that, at a community level, the spectrum of HIV risk
      reduction programs does produce a significant improvement in condom use and
      related cognitions, although there is a need to cover a greater proportion of the
      population. Previous exposure to interventions must be a critical covariate in
      assessing the impact of future interventions.

PMID- 17505922
TI  - Evaluation of the consistency of refills for antiretroviral medications in two
      hospitals in the state of Rio de Janeiro, Brazil.
AB  - We conducted a retrospective cohort study using pharmacy records to assess the
      frequency of delay in picking up antiretroviral (ARV) medication refills from the
      pharmacy and to identify determinants of delay among HIV-infected patients at two
      Brazilian hospitals. We selected patients who were on ARV therapy before January
      2001 at Nova Iguacu Hospital (NIPRH) (N = 265) and Evandro Chagas (N=424)
      Clinical Research Institute. We abstracted medical records and pharmacy data
      using standardised forms and analysed potential associations between delay in
      refilling medications and patients' demographic characteristics, type of ARV drug
      regimen and evolution of HIV disease. Sixty-nine patients (26%) had delays in
      medication refills >1 month at least once in 2001 at NIPRH compared with 140
      (33%) patients at IPEC (p=0.052). No factor was found to be associated with
      having a delay in medication refill >1 month at NIPRH. At IPEC, delays in
      medication refill >1 month were associated with a median CD4+ T cell count
      <200/mm(3) versus >500/mm(3) (adjusted odds ratio (AOR) = 3.8; 95% confidence
      interval (CI) =1.6-8.9) and with dual protease inhibitor-based ARV regimens
      versus other regimens (AOR = 4.3; 95% CI = 1.9-9.4). In conclusion, rates of
      delay in medication refills were similar to rates of adherence to ARV therapy
      found in other studies in Brazil, suggesting that delay in medication refills
      could be used as a surrogate for adherence. Analysing ARV medication refills can
      complement self-reported information on adherence.

PMID- 17505923
TI  - Trends and predictors of quality of life among HIV-infected adults taking highly
      active antiretroviral therapy in rural Uganda.
AB  - We examined trends and predictors of quality of life (QOL) over 12 months among a
      prospective cohort of 947 HIV-1-infected adults initiating highly active
      antiretroviral therapy (HAART) between May 2003 and May 2004 in rural Uganda.
      Participants provided clinical, demographic and psychosocial data at baseline and
      every three months thereafter. Outcome measures included physical and mental
      health summary scores based on the Medical Outcomes Study-HIV Health Survey (MOS
      HIV). Generalised estimating equations were used to assess magnitude of change in
      summary scores and factors associated with QOL. Of 710 women and 237 men
      enrolled, the mean age was 38.7 years and mean baseline CD4 cell count was 124.1
      cells/microL. At enrollment, physical and mental health summary scores were 39.2
      and 40, respectively. By 12 months of HAART, scores increased by 11.2 points (p
      <0.001) and 7.4 points (p <0.001), respectively. For both scores, most gains were
      achieved by the third month of therapy. While several clinical, psychosocial and
      sociodemographic factors predicted QOL at HAART initiation, financial dependence
      on others was the only remaining predictor after controlling for time on HAART.
      Interventions to enhance the economic and employment opportunities of patients
      taking HAART in rural Africa may help maximise gains in QOL.

PMID- 17505924
TI  - Early immunologic and virologic responses to highly active antiretroviral therapy
      and subsequent disease progression among HIV-infected injection drug users.
AB  - We examined the prevalence and prognostic value of early responses to highly
      active antiretroviral therapy (HAART) among community-based injection drug users
      (IDUs) in Baltimore. Virologic (HIV RNA <1000 copies/ml) and immunologic (CD4
      >500 cells/ul or increase of 50 cells/ul from the pre-HAART level) responses were
      examined in the 1st year of HAART initiation. Cox regression was used to examine
      the effect of early response on progression to new AIDS diagnosis or AIDS-related
      death. Among 258 HAART initiators, 75(29%) had no response, 53(21%) had a
      virologic response only, 38(15%) had an immunologic response only and 92(36%) had
      a combined immunologic and virologic response in the first year of therapy.
      Poorer responses were observed in those who were older, had been recently
      incarcerated, reported injecting drugs, had not had a recent outpatient visit and
      had some treatment interruption within the 1st year of HAART. In multiple Cox
      regression analysis, the risk of progression was lower in those with combined
      virologic and immunologic response than in non-responders, (relative hazard [RH],
      0.32; 95% confidence interval [CI], 0.17-0.60). Those with discordant responses
      had reduced risk of progression compared to non-responders but experienced faster
      progression than those with a combined response, although none of these
      differences was statistically significant. Early discordant and non response to
      HAART was common, often occurred in the setting of injection drug use and
      treatment interruption and was associated with poorer survival. Interventions to
      reduce treatment interruptions and to provide continuity of HIV care during
      incarceration among IDUs are needed to improve responses and subsequent survival.

PMID- 17505925
TI  - Home deliveries: implications for adherence to nevirapine in a PMTCT programme in
      rural Malawi.
AB  - Although nevirapine (NVP) is provided by prevention of mother-to-child
      transmission (PMTCT) of HIV programmes to be taken at onset of labor independent
      of place of delivery, few studies have assessed adherence to NVP outside the
      hospital setting. This study aimed to follow women in a PMTCT programme up to
      delivery and to assess the adherence to the prophylaxis in rural Malawi. A total
      of 75 HIV-positive women were registered in the PMTCT at Malamulo SDA hospital
      between January and June 2005. Forty women (53%) delivered in the hospital and 35
      (47%) did not. Of the 35 women who delivered at home, it was possible to trace 27
      (77.2%). All women who delivered in the hospital took their NVP tablets and all
      their babies had NVP syrup except one baby who died soon after delivery. Of the
      27 traced women who had not delivered in the hospital, 16 (59.3%) had access to
      NVP and had taken their tablets during labor. However, none of their babies was
      taken back to the health facility for NVP syrup. Traditional birth attendants
      might be crucial in efforts aiming to increase adherence to NVP among women and
      their babies.

PMID- 17505926
TI  - Identification of beneficiaries of free anti-retroviral drugs in Malawi: a
      community consensus process.
AB  - Malawi is a southeastern Africa country that has been heavily affected by the
      AIDS pandemic. It is estimated that about 170,000 people were in need of highly
      active antiretroviral therapy (HAART) for the treatment of AIDS in 2006. At the
      end of 2006, at least 55,000 people in Malawi were on HAART treatment, mostly
      through the free public sector program. At the time the program was being
      initiated, an ethical question needed to be answered in respect to who would be
      targeted for free treatment in an environment where medications, human and other
      resources were not enough to cater for all who were clinically eligible to be on
      treatment. In this paper we report on a qualitative study that was carried out to
      obtain public perceptions and input as to which criteria ought to have been
      applied to identify persons or groups of persons to be targeted in the free HAART
      program. In general, there was no agreement as to who should be prioritised for
      HAART, whether treatment should be free to user or whether cost-sharing should be
      introduced. While it may have been relatively straightforward in obtaining
      consensus and agreement among medical practitioners on the clinical criteria for
      HART in Malawi, deciding on the social criteria was complex. The decision to
      start the nationwide HAART program was started with the understanding that
      virtually every social group could be justified as worth of free HAART.

PMID- 17505927
TI  - Hunger, waiting time and transport costs: time to confront challenges to ART
      adherence in Africa.
AB  - Adherence levels in Africa have been found to be better than those in the US.
      However around one out of four ART users fail to achieve optimal adherence,
      risking drug resistance and negative treatment outcomes. A high demand for 2nd
      line treatments (currently ten times more expensive than 1st line ART) undermines
      the sustainability of African ART programs. There is an urgent need to identify
      context-specific constraints to adherence and implement interventions to address
      them. We used rapid appraisals (involving mainly qualitative methods) to find out
      why and when people do not adhere to ART in Uganda, Tanzania and Botswana.
      Multidisciplinary teams of researchers and local health professionals conducted
      the studies, involving a total of 54 semi-structured interviews with health
      workers, 73 semi-structured interviews with ARTusers and other key informants, 34
      focus group discussions, and 218 exit interviews with ART users. All the
      facilities studied in Botswana, Tanzania and Uganda provide ARVs free of charge,
      but ART users report other related costs (e.g. transport expenditures,
      registration and user fees at the private health facilities, and lost wages due
      to long waiting times) as main obstacles to optimal adherence. Side effects and
      hunger in the initial treatment phase are an added concern. We further found that
      ART users find it hard to take their drugs when they are among people to whom
      they have not disclosed their HIV status, such as co-workers and friends. The
      research teams recommend that (i) health care workers inform patients better
      about adverse effects; (ii) ART programmes provide transport and food support to
      patients who are too poor to pay; (iii) recurrent costs to users be reduced by
      providing three-months, rather than the one-month refills once optimal adherence
      levels have been achieved; and (iv) pharmacists play an important role in this
      follow-up care.

PMID- 17505928
TI  - The effects of individual- and community-level knowledge, beliefs, and fear on
      stigmatization of people living with HIV/AIDS in China.
AB  - This paper assesses the effects of individual- and community-level knowledge of
      HIV transmission, beliefs and fear of infection on individual attitudes toward
      and willingness to interact with people living with HIV/AIDS in China. Data are
      from a sample survey of 12,270 men and women age 15-49 from seven
      provinces/municipalities. The survey was conducted by the Population and Family
      Planning Commission in December 2003. Multilevel regression analyses show that
      stigmatization of people living with HIV/AIDS is strongly associated with
      community-level HIV knowledge and fear, even after taking into account HIV
      knowledge and fear at the individual level. The findings suggest that individual
      attitudes are partially shaped through social learning and social influence.
      Public-health interventions aimed at eliminating stigmatization of people living
      with HIV/AIDS will need to pay special attention to social and community
      influences while continuously working to enhance HIV knowledge and reduce
      inaccurate beliefs and fear.

PMID- 17505929
TI  - Mental health in HIV-positive pregnant women: results from Angola.
AB  - Our objective was to assess the mental health status of pregnant women who are
      HIV-positive, compared with other groups of pregnant women. We evaluated pregnant
      HIV-positive women attending the Medecins Sans Frontiers (MSF) HIV clinic in
      Malanje, Angola (N = 23). The control group consisted of pregnant women coming
      for antenatal clinic consultations who were not known to be HIV-positive (N=134).
      To assess mental health, the 12-item General Health Questionnaire (GHQ-12) was
      used. A score of three or greater was considered to indicate significant
      emotional distress. We also examined determinants of emotional distress in
      logistic multivariate regression models. We found that the mean score on the GHQ
      12 for the HIV-positive group was more than twice the mean score of the controls,
      indicating poorer mental health in the HIV-positive group. Two-thirds of HIV
      positive women had significant emotional distress, more than twice that in the
      control group. As well as HIV status, marital status was a strong independent
      predictor of mental health status, with married women experiencing less emotional
      distress. Thus, in our sample, pregnant women who were HIV-positive had a much
      poorer mental health status than the controls. Strategies to improve the mental
      health of HIV-positive mothers must be implemented and evaluated; efforts to
      decrease the levels of stigma and discrimination in this population are of key
      importance.

PMID- 17505930
TI  - Theory of planned behaviour predictors of intention to use condoms among Xhosa
      adolescents in South Africa.
AB  - HIV/AIDS is taking a heavy toll on South African youth. Reducing their risk for
      HIV requires an understanding of the determinants of their HIV risk behaviours
      that are amendable to intervention-induced change. This study draws upon the
      theory of planned behaviour to identify the modifiable determinants of the
      intention to use condoms among Xhosa-speaking South African adolescents. The
      participants were 390 Xhosa-speaking 6th grade students (mean age = 12.1 years)
      in public schools in the township of Mdantsane, South Africa who completed an
      anonymous questionnaire. Multiple regression revealed that attitude and perceived
      behavioural control were significantly related to the intention to use condoms,
      whereas subjective norm was not, controlling for sexual experience, gender, and
      language preference. Consistent with this were additional analyses using beliefs
      as predictors: Hedonistic behavioural beliefs and control beliefs about condom
      use negotiation and technical skills predicted intention, whereas normative
      beliefs did not. The theory of planned behaviour may be a useful model of condom
      use among Xhosa-speaking South African adolescents. An emphasis on beliefs about
      the adverse effects of condom use on sexual enjoyment, the ability to negotiate
      condom use, and the ability to use condoms correctly might improve the efficacy
      of HIV/STD interventions for such adolescents.

PMID- 17505931
TI  - Chinese health care providers' attitudes about HIV: a review.
AB  - China has one of the fastest growing HIV epidemics in the world with an increase
      in reported cases of about 30% yearly (UNAIDS, 2004). As the epidemic has grown,
      there have been several studies of health care provider attitudes towards HIV in
      China over the last 15 years. While attitudes have evolved, misconceptions about
      transmission of HIV, low levels of support for people living with HIV/AIDS and
      stigmatized groups, and a poor understanding of the importance of condoms in HIV
      prevention, remain. The studies are limited by a weakness of survey instruments
      and an absence of focus on the gendered nature of the HIV epidemic.
      Recommendations for future research in this area include development of a
      theoretical base, consideration of gender and stigma, and incorporation of these
      issues into the survey instruments.

PMID- 17505932
TI  - Reliability, sensitivity and specificity of self-report of HIV test results.
AB  - The objective of the study was to assess the reliability and validity of self
      report of HIV testing questions on the Risk Behavior Assessment and Risk Behavior
      Follow-up Assessment. Study 1 had 219 injection drug users and crack cocaine
      smokers. Study 2 had 259 injection drug users and crack cocaine smokers. Study 3
      had data from 17,408 injection drug users and crack cocaine smokers. When the
      question 'Have you ever been told that you were infected with the AIDS virus' was
      compared to ELISA result, the specificity was over 99% for both baseline and
      follow-up. The sensitivity was 32% on the Risk Behavior Assessment, but 61% on
      the Risk Behavior Follow-up Assessment. Those who were HIV positive at Risk
      Behavior Assessment (baseline) were less likely to have received their previous
      HIV test result. Two-thirds of the HIV test-related questions on the Risk
      Behavior Assessment and Risk Behavior Follow-up Assessment had acceptable
      reliability. The low sensitivity at Risk Behavior Assessment was probably due to
      the participants' failure to receive their previous test results.

PMID- 17505935
TI  - The latest elaboration of the Women's Health Initiative data on hormone
      replacement therapy and cardiovascular disease in postmenopausal women.

PMID- 17505933
TI  - Pro-social and problematic social network influences on HIV/AIDS risk behaviours
      among newly homeless youth in Los Angeles.
AB  - We examined the social network composition among newly homeless youth over time
      and assessed how pro-social and problematic peers affected sexual and drug-using
      HIV/AIDS risk-behaviours among 183 youth in Los Angeles County, California. The
      percentage of newly homeless youth who reported that 'most' or 'all' of their
      friends were attending school, had jobs, and got along with their families was
      73%, 24%, and 50% respectively. Logistic regression models indicated that
      presence of these pro-social peers reduced HIV risk behaviours at two years; odds
      of HIV-risk were lower with a greater number of peers who attend school, have a
      job, or have positive family relationships or if networks change over time to
      include more of these peers. Presence of problematic peers increased the
      likelihood of HIV risk-taking; odds of HIV risk behaviours increased with a
      greater number of peers at baseline who steal, have overdosed, have been
      arrested, or are in a gang, or if networks change to include more of these peers.
      Interventions should target newly homeless youth in networks that contain
      problematic peers, but should strive to harness the naturally occurring pro
      social peer influences present in these networks.

PMID- 17505936
TI  - Progesterone and progesterone receptor modulator in uterine leiomyoma growth.

PMID- 17505937
TI  - Expression of 17beta-hydroxysteroid dehydrogenase type 2 in pelvic endometriosis.
AB  - Lack of expression or a deficiency of 17beta-hydroxysteroid dehydrogenase type 2
      (17beta-HSD2), a key enzyme in estradiol inactivation, could be involved in the
      pathophysiology of endometriosis. The aim of the present study was to evaluate
      expression of the gene (17beta-Hsd2) encoding 17beta-HSD2 in eutopic and ectopic
      endometrial tissues of women with endometriosis. Thirty-four infertile women were
      divided into a control group, without any clinical or laparoscopic evidence of
      endometriosis (n = 19), and a group with pelvic endometriosis (n = 15). Diagnosis
      was confirmed by histological examination of the endometriotic lesions. 17beta
      Hsd2 mRNA expression was detected by reverse transcription-polymerase chain
      reaction in the control group (54% of the samples), in the eutopic endometrium of
      patients with endometriosis (83% of the specimens analyzed) and in all
      endometriotic lesions. The semi-quantitative analysis of 17beta-Hsd2 mRNA showed
      a significantly higher gene expression in the endometriotic implants compared
      with the intrauterine endometrium of the control group (p < 0.05). 17beta-HSD2
      protein was localized to the glandular epithelium of both eutopic endometrium and
      endometriotic implants. The present results refute the hypothesis of lower or
      absent 17beta-HSD2 expression in pelvic endometriosis; therefore further studies
      are needed to assess other potential mechanisms leading to increased estrogenic
      activity within endometriotic implants.

PMID- 17505938
TI  - Antiandrogenic activity of norgestimate in a human androgen-dependent stable
      transfected cell line.
AB  - BACKGROUND: Acne occurs from an overstimulation of the sebaceous glands by high
      levels of androgens or because sebaceous glands are hypersensitive to normal
      levels of testosterone. In women with moderate acne, norgestimate (NG) in
      association with ethinyl estradiol (EE) is acknowledged as an effective
      treatment; this is related to the effect of oral contraceptives on androgen
      production and transport. However, the antiandrogenic properties of NG itself
      have been poorly studied. DESIGN: The present work was undertaken to find out
      whether NG and its derivative, 17-deacetylnorgestimate (dNG), present
      antiandrogen activity. First, we studied the effect of NG and dNG on the
      intracellular localization of green fluorescent protein (GFP)-labeled androgen
      receptor (AR). Then, we compared the AR activity of NG and dNG with that of
      cyproterone acetate (CPA), a gold-standard antiandrogenic compound, by
      investigating competitive binding, antagonist activity and transactivation level
      of AR. RESULTS: NG and dNG decreased GFP-AR nuclear translocation, revealing
      their antiandrogenic property, as for CPA. In the whole cell competition assay
      performed in a human cell line stably expressing an AR-responsive luminescent
      reporter gene (PALM cells) with (3)H-labeled R1881 as tracer, NG and dNG were
      slightly stronger competitors than the antiandrogen CPA. Half-maximal inhibition
      (K(i)) of (3)H-labeled R1881 (10(-9) M) binding occurred at 4.2 +/- 0.5 x 10(-8)
      M of NG, 3.4 +/- 0.4 x 10(-8) M of dNG and 6.6 +/- 0.8 x 10(-8) M of CPA.
      Comparison of antagonist activities of NG, dNG and CPA on AR transactivation
      levels showed that NG, dNG and CPA inhibited androgen-induced luciferase activity
      in PALM cells. We observed slight and similar inhibition with 6 x 10(-8) M
      respectively of NG, dNG and CPA. For the three compounds, the best inhibitory
      effect was found at 3 x 10(-7) M: 24% for NG and dNG vs. 47% for CPA. The
      antiandrogenic activity of NG and dNG was found to be 50% that of CPA.
      CONCLUSION: In a human androgen-dependent stable-transfected cell line, a useful
      tool for studying AR transcriptional activity and its subnuclear localization in
      the presence of androgens and antiandrogens, we demonstrated that NG and dNG have
      antiandrogenic properties that could partly explain the efficacy of NG in
      association with EE for the treatment of moderate acne in women.

PMID- 17505939
TI  - Menopause symptoms in women infected with HIV: prevalence and associated factors.
AB  - OBJECTIVE: To evaluate the prevalence and factors associated with menopause
      symptoms in HIV-infected women. METHODS: A cross-sectional study of two groups of
      women was conducted: 96 with HIV and 155 without HIV. Women aged 40 years or
      older, non-users of hormone therapy in the last 6 months and native Brazilians
      were included. The prevalence of menopause symptoms was calculated according to
      the studied variables. Symptoms were grouped into six categories: vasomotor,
      psychological, genitourinary, weight gain, palpitations and insomnia. The
      generalized estimating equation model was applied to identify the factors
      associated with menopause symptoms in all women and for HIV-infected women only.
      RESULTS: The mean (+/-standard deviation) age of women with and without HIV was
      48.9 +/- 7.4 and 51.0 +/- 8.7 years (p = 0.07), respectively. The median age at
      menopause for HIV-infected women was 47.5 years. Menopause symptoms were more
      frequent in HIV-infected women, highlighting psychological and vasomotor
      symptoms. HIV infection was associated with menopause symptoms (odds ratio (OR) =
      1.65, p = 0.03), as well as age ranging from 45 to 54 years (OR = 1.77, p =
      0.01), higher parity (OR = 2.38, p = 0.01) and self-perception of health as
      fair/poor (OR = 2.07, p < 0.01). Among HIV-infected women, the likelihood of
      presenting symptoms decreased in those aged 55 or older (OR = 0.16, p = 0.03) and
      increased in retired women (OR = 2.61, p = 0.02). CONCLUSION: Menopause symptoms
      were common in HIV-infected women. HIV infection was independently associated
      with menopause symptoms, whereas age and being retired were associated with the
      occurrence of these symptoms in HIV-infected women.

PMID- 17505940
TI  - Sonographic assessment of ovarian reserve. Its correlation with outcome of in
      vitro fertilization cycles.
AB  - Ovarian reserve is a crucial factor for normal ovarian response and the
      achievement of pregnancy after in vitro fertilization (IVF). Recently, the study
      of morphological markers by means of ultrasonographic counting of antral
      follicles (AFC) has proved useful. The present prospective study included 327
      consecutive IVF patients who had a basal ultrasound scan of their ovarian reserve
      during the early follicular phase and had a first IVF cycle between 1 and 3
      months later. We performed 313 ovum pick-ups with a mean of 11.1 +/- 7.9 oocytes
      retrieved. The pregnancy rate per aspiration was 34.5%. Clear and significant
      differences were observed between normal and low response with respect to AFC,
      follicle-stimulating hormone (FSH) level and age. We also found that AFC
      correlated negatively and significantly with age, FSH and LH, and positively and
      also significantly with the total number of follicles, estradiol level and the
      number of oocytes retrieved. Using receiver operating characteristic curves, the
      cut-off value of AFC for poor response was 7 follicles. The value of AFC for
      predicting pregnancy was lower, although patients with AFC of 8 or more follicles
      obtained significantly higher pregnancy rates. We consider that AFC should be
      included in the study of the infertile patient.

PMID- 17505941
TI  - Elaboration of a working model for the involvement of inhibin A as a mediator of
      the preovulatory rise of progesterone levels.
AB  - During the final days of follicular development, exogenously administered
      follicle-stimulating hormone (FSH) produces a rise in serum progesterone level.
      The aim of the present study was to investigate the possible source and
      regulation of this preovulatory progesterone surge. Four sets of matching
      treatments with gonadotropins for in vitro fertilization and intracytoplasmic
      sperm injection were selected from a cohort of 953 treatments in 244 couples.
      Half of these four sets of treatments were selected based on the unusual course
      of the progesterone concentration during follicular development. The first set of
      11 cycles with early termination of gonadotropin administration for prolonged
      coasting were compared with a set of 12 cycles with similar estradiol levels but
      with uninterrupted ovarian stimulation. Another set of 12 cycles with low
      preovulatory progesterone levels (<2 nmol/l) were matched with ten cycles with
      normal preovulatory progesterone levels (>2 nmol/l). The sera of these four
      selected sets of treatments were stored for subsequent measurement of the
      concentrations of inhibin A, inhibin B, activin A and leptin. During ovarian
      hyperstimulation serum levels of inhibin A correlated significantly with those of
      progesterone (p < 0.001), whereas this correlation disappeared after the
      withdrawal of FSH administration. The rapid fall of progesterone levels during
      prolonged coasting contrasts with the continuing rise of estradiol concentration
      and indicates that the theca interna, not the granulosa, is the major source of
      preovulatory progesterone. Women failing to produce any increment of progesterone
      levels at the end of follicular development had significantly lower levels of
      inhibin A (p < 0.05), indicating that inhibin A may well be involved in mediating
      the signal of FSH from the granulosa to the theca interna.

PMID- 17505942
TI  - The role of progesterone in endometrial estradiol- and progesterone-receptor
      synthesis in women with menstrual disorders and habitual abortion.
AB  - The objective of this comparative study was to determine the influence of changes
      in estradiol and progesterone during ovulatory vs. anovulatory cycles on levels
      of estradiol receptor (ER) and progesterone receptor (PgR) in endometrium. Thirty
      women (range age 20-35 years) were divided into three groups: women with a
      history of habitual abortion, obese women with menstrual disorders, and women
      with regular ovulatory cycles as well as proven fertility. A single venous blood
      sample and an endometrial sample were simultaneously obtained during the
      secretory phase of the menstrual cycle, in order to measure estradiol and
      progesterone levels and ER and PgR concentrations in cytosol and salt-extracted
      nucleosol. Plasma estradiol levels were not different between groups. Plasma
      progesterone was two times higher in fertile women than in habitual aborters. In
      endometrial tissue, progesterone content was 200 times higher in fertile women
      than in habitual aborters. ER and PgR were lower in the cytosol than in the
      nuclear fraction in fertile and obese women. Both receptors were at their lowest
      level in the cytosol and nuclear compartment of women with recurrent miscarriage.
      Fluctuations mainly in the sex hormone progesterone, in plasma and endometrium
      tissue, could interfere with ER and PgR levels.

PMID- 17505943
TI  - The usefulness of a thyrotropin-releasing hormone stimulation test in subfertile
      female patients.
AB  - BACKGROUND: The thyrotropin-releasing hormone (TRH) stimulation test is widely
      used as a screening procedure in subfertile patients to identify subclinical
      hypothyroidism. However, its usefulness in daily clinical practice has not been
      proven, despite more than 30 years of use. MATERIAL AND METHODS: We analyzed data
      from a cohort of 371 consecutive female subfertility patients, who were screened
      with an intravenous TRH test when they came for the first evaluation. All
      patients with positive thyroid peroxidase antibodies, basal TSH <1.5 mU/l, known
      thyroid disease or actual thyroid medication were not screened and excluded from
      the analysis. RESULTS: We found a good correlation between basal and stimulated
      levels of thyroid-stimulating hormone (TSH). Basal TSH and the difference between
      stimulated and basal TSH did not correlate with prolactin levels. Definition of a
      positive TRH test (difference of 15 or 20 mU/l) did not have sufficient
      sensitivity and specificity, as confirmed by analysis of receiver operating
      characteristic curves, to identify subclinical hypothyroidism. CONCLUSION: TRH
      stimulation testing is not helpful to identify patients with subclinical
      hypothyroidism and should not be part of initial screening in this group.

PMID- 17505944
TI  - Effects of metformin treatment in women with polycystic ovary syndrome depends on
      insulin resistance.
AB  - Polycystic ovary syndrome (PCOS) affects 5-10% of women at reproductive age, and
      is the most common reason for hyperandrogenism and chronic anovulation. Some
      patients with PCOS are insulin-resistant. Also, lowered sex hormone-binding
      globulin (SHBG) concentration is usually observed. As a consequence, the amount
      of free and biologically active androgens increases. This implies that, by
      improving insulin and carbohydrate metabolism, metformin administration in PCOS
      patients could indirectly contribute to increase SHBG concentration. The aim of
      the present study was to assess the effects of metformin treatment in PCOS
      patients both with and without insulin resistance. Thirty-six patients completed
      treatment. Body mass index (BMI) was considerably reduced after therapy.
      Statistically significant decreases were noted in luteinizing hormone (LH) and
      fasting insulin concentrations and the free androgen index (FAI), and significant
      increases in follicle-stimulating hormone (FSH)/LH ratio and SHBG concentration.
      In the insulin-resistant group, BMI and fasting insulin concentrations were
      reduced considerably after treatment, and SHBG increased slightly. In the group
      of patients without insulin resistance, BMI, LH and FAI showed significant
      reductions, and FSH/LH and SHBG considerable increases. Considering the favorable
      effects of metformin treatment in PCOS patients both with insulin resistance and
      without it, it is purposeful to use this drug in both groups of women.

PMID- 17505945
TI  - Plasma adiponectin concentrations and placental adiponectin expression in pre
      eclamptic women.
AB  - This study was conducted to compare maternal plasma adiponectin concentrations
      and adiponectin expression in term placentas between normotensive pregnant women
      and pre-eclamptic women. Plasma adiponectin concentrations were assessed by a
      sandwich enzyme-linked immunosorbent assay in 81 normotensive pregnant women, 27
      pre-eclamptic women and 15 non-pregnant healthy women. The expression of
      adiponectin in the placentas was assessed by immunohistochemistry. Plasma
      adiponectin concentrations in normotensive pregnant women did not show a
      significant change during pregnancy and postpartum compared with non-pregnant
      women. However, plasma adiponectin concentrations in pre-eclamptic women were
      significantly (p < 0.05) lower than in non-pregnant and normotensive pregnant
      women. No immunoreactive adiponectin was detected in the term placentas of
      normotensive pregnant women, whereas a positive immunostaining for adiponectin
      was observed in endothelial cells of chorionic vessels in pre-eclamptic women.
      Our data suggest that decreased plasma adiponectin concentrations may contribute
      to the pathophysiology of pre-eclampsia and that adiponectin localized in
      chorionic vessels may play a role in the restoring of endothelial damage in the
      feto-maternal units of pre-eclampsia.

PMID- 17505948
TI  - Whither Latin America? Trends and challenges of science in Latin America.
AB  - Science in Latin America has experienced vigorous growth in the past decade, as
      demonstrated by the fact that the Latin American share of the world's scientific
      publications increased from 1.8% in 1991-1995 to 3.4% in 1999-2003. Significant
      growth has also taken place in the numbers of PhDs in science and engineering
      (S&E) awarded in Latin American countries in recent years, including those in the
      natural sciences. Importantly, albeit at different rates, growth has been
      verified in almost all countries in the region, indicating a general effort to
      promote the development of S&E. In most research fields, however, the recognition
      or relative impact of Latin American science, as measured by the average number
      of citations received by published articles (CpP), is still below world averages
      and much lower than in developed nations. We show that average CpP values for a
      set of 34 representative developing and developed countries correlate
      significantly with gross expenditure in research and development (GERD), with
      gross domestic product (GDP) per capita and with the number of researchers per
      million inhabitants (RpM). Among those countries, Latin American nations present
      some of the lowest average values of CpP (<6), GERD (< or =1% of GDP) and RpM
      (<2,000). We also examined recent trends in scientific activity in Latin America,
      with focus on the natural sciences and on biochemistry and molecular biology
      (BMB). In terms of citation scores, publications in BMB compare favorably to
      those in other research fields within Latin America. At the same time, however,
      Latin American BMB is one of the areas for which relative impact--compared to
      developed nations or normalized to world averages--is lowest. These observations
      clearly indicate the need to establish effective policies to increase
      competitiveness in terms of the quality and international recognition of Latin
      American natural sciences in general, and BMB in particular, as opposed to merely
      increasing the absolute numbers of publications or the numbers of PhDs awarded in
      the region.

PMID- 17505957
TI  - The impact of science in Brazil.

PMID- 17505958
TI  - On intelligent design, cognitive relativism, vitalism and the mystery of the real
      world.

PMID- 17505959
TI  - Autophagy: a pathogen driven process.
AB  - Host cell recognition and eradication of invading pathogens is crucial for the
      control of microbial infections. However, several microorganisms develop tactics
      that allow them to survive intracellularly. Autophagy, a process involved in
      protein turnover and in charge of the removal of aged organelles by degradation
      of engulfed cytoplasmic portions, was recently shown to play a clear role in the
      detection and elimination of intracellular pathogens. Yet, some pathogens employ
      elegant strategies to elude entrapment in autophagosomes, and thus to avoid
      lysosomal degradation, whereas others utilize the autophagy pathway for their own
      benefit. In this review some recent findings on the relationship between
      microorganisms and autophagy are summarized, the underlying assumption being that
      intracellular infection models may contribute to the understanding of the
      molecular mechanisms involved in the autophagic process.

PMID- 17505960
TI  - Acceleration of nitric oxide autoxidation and nitrosation by membranes.
AB  - The reaction between nitric oxide ((.)NO) and oxygen yields reactive species
      capable of oxidizing and nitrosating proteins, as well as deaminating DNA bases.
      Although this reaction is considered too slow to be biologically relevant, it has
      been shown that membranes, lipoproteins, mitochondria and possibly proteins can
      accelerate this reaction. This effect stems from the higher solubility of both
      (.)NO and O(2)in the hydrophobic phase of these biological particles, leading to
      a concentration of both reagents and so a higher rate of reaction. It has been
      determined that this reaction occurs from 30 to 300 times more rapidly within the
      membrane, while even higher values have been suggested for proteins. The
      autoxidation of (.)NO in membranes is not the main route for cellular (.)NO
      consumption but an important consequence of this phenomenon is to focus the
      generation of significant amounts of oxidizing and nitrosating molecules
      (nitrogen dioxide and dinitrogen trioxide) in the small volume comprised by
      cellular membranes. Even so, these reactive species are diffusible and their
      ultimate fate will depend on the reactivity towards available substrates rather
      than on physical barriers. The acceleration of (.)NO autoxidation by biological
      hydrophobic phases may thus be a general phenomenon that increases in importance
      in cases of (.)NO overproduction.

PMID- 17505961
TI  - Theories of ageing.
AB  - Ageing is a universal, intrinsic, progressive and deleterious process.
      Understanding it is of major interest to scientist, physicians as well as to the
      general population. Critical to this understanding is to formulate comprehensive
      theories of aging with high predictive and explanatory power. More than 300
      theories have been postulated and are reviewed here. The free radical theory of
      ageing is one of the most prominent and well studied. It was further developed by
      one of us (JM) in what has become known as the mitochondrial theory of ageing.
      These theories provide new experimental approaches to further develop our
      understanding of the phenomenon of ageing.

PMID- 17505962
TI  - The carbonate radical and related oxidants derived from bicarbonate buffer.
AB  - The unequivocal demonstration that the carbonate radical (CO(3) (.-)) is produced
      from the reaction between the ubiquitous carbon dioxide and peroxynitrite,
      renewed the interest in the pathogenic roles of oxidants derived from the main
      physiological buffer, the bicarbonate-carbon dioxide pair. Here, we review the
      biochemical properties of both the carbonate radical and peroxymonocarbonate
      (HCO(4) (-)), and discuss the evidence of their formation under physiological
      conditions. Overall, the review emphasizes the recognition of the biological
      relevance of oxidants derived from the main physiological buffer as a crucial
      step into the understanding and control of numerous pathological states.

PMID- 17505963
TI  - Mitochondrial energy metabolism and redox state in dyslipidemias.
AB  - Changes in mitochondrial function are intimately associated with metabolic
      diseases. Here, we review recent evidence relating alterations in mitochondrial
      energy metabolism, ion transport and redox state in hypercholesterolemia and
      hypertriglyceridemia. We focus mainly on changes in mitochondrial respiration,
      K(+) and Ca(2+) transport, reactive oxygen species generation and susceptibility
      to mitochondrial permeability transition.

PMID- 17505964
TI  - Expression of cancer-associated simple mucin-type O-glycosylated antigens in
      parasites.
AB  - Simple mucin-type O-glycan structures, such as Tn, TF, sialyl-Tn and Tk antigens,
      are among of the most specific human cancer-associated structures. These antigens
      are involved in several types of receptor-ligand interactions, and they are
      potential targets for immunotherapy. In the last few years several simple mucin
      type O-glycan antigens were identified in different species belonging to the main
      two helminth parasite phyla, and sialyl-Tn bearing glycoproteins were detected in
      Trypanosoma cruzi. These results are of interest to understand new aspects in
      parasite glycoimmunology and may help identify new biological characteristics of
      parasites as well of the host-parasite relationship. Considering that different
      groups reported a negative correlation between certain parasite infections and
      cancer development, we could hypothesize that simple mucin-type O-glycosylated
      antigens obtained from parasites could be good potential targets for cancer
      immunotherapy.

PMID- 17505965
TI  - Trypanosoma cruzi: adhesion to the host cell and intracellular survival.
AB  - Both invasion of the host cell by T. cruzi and its establishment into the
      mammalian host are critical steps. In this review, the adhesion step and the
      intracellular survival in non-professional phagocytes are particularly focused
      on, with special emphasis on the role of Gp85/trans-sialidase (Gp85/TS)
      superfamily. Excellent reviews have been published lately, some covering other
      aspects of T. cruzi-host interaction and will be cited instead of the original
      articles due to limited number of listed references.

PMID- 17505966
TI  - Calcium, iron and neuronal function.
AB  - Calcium and iron play dual roles in neuronal function: they are both essential
      but when present in excess they cause neuronal damage and may even induce
      neuronal death. Calcium signals are required for synaptic plasticity, a neuronal
      process that entails gene expression and which is presumably the cellular
      counterpart of cognitive brain functions such as learning and memory. Neuronal
      activity generates cytoplasmic and nuclear calcium signals that in turn stimulate
      pathways that promote the transcription of genes known to participate in synaptic
      plasticity. In addition, evidence discussed in this article shows that iron
      deficiency causes learning and memory impairments that persist following iron
      repletion, indicating that iron is necessary for normal development of cognitive
      functions. Recent results from our group indicate that iron is required for long
      term potentiation in hippocampal CA1 neurons and that iron stimulates ryanodine
      receptor-mediated calcium release through ROS produced via the Fenton reaction
      leading to stimulation of the ERK signaling pathway. These combined results
      support a coordinated action between iron and calcium in synaptic plasticity and
      raise the possibility that elevated iron levels may contribute to neuronal
      degeneration through excessive intracellular calcium increase caused by iron
      induced oxidative stress.

PMID- 17505967
TI  - Acrosomal exocytosis, a special type of regulated secretion.
AB  - The acrosome is a single secretory granule present in the head of mammalian--and
      other animal groups--sperm. Secretion of this granule is an absolute requirement
      for physiological fertilization. Acrosome exocytosis is a synchronized and
      tightly regulated all-or-nothing process, with no recycling of membranes. In the
      last few years, it has been shown that acrosomal exocytosis is mediated by a
      molecular mechanism that is homologous to that reported in the secretion of
      neuroendocrinal cells. Moreover, because of its particular characteristics,
      acrosomal exocytosis is a unique mammalian model for the study of the different
      steps of the membrane fusion cascade. Combining results in intact and
      permeabilized sperm, the following sequence of events has been proposed. In
      resting sperm, SNARE proteins are locked in inactive cis complexes. Sperm
      activation causes a calcium increase in the cytoplasm that promotes the
      production of cAMP and activates Rab3A. Afterwards, NSF and alphaSNAP disassemble
      cis complexes and the free SNAREs are then able to reassemble in loose trans
      complexes. Membrane fusion is arrested at this stage until calcium is released
      from inside the acrosome by inositol 1,4,5-trisphosphate-sensitive calcium
      channels to trigger the final steps of membrane fusion, which require fully
      assembled trans SNARE complexes and the calcium sensor synaptotagmin. This
      working model is still incomplete and tentative. Its improvement will be
      important to share light on this and other processes of regulated exocytosis.
      Moreover, it will bring new perspectives into the field of sperm-related
      fertility and sterility.

PMID- 17505968
TI  - Protein oxidation, repair mechanisms and proteolysis in Saccharomyces cerevisiae.
AB  - Reactive oxygen species, generated as normal by-products of aerobic metabolism or
      due to cellular stress, oxidize molecules and cause cell death by apoptosis. The
      accumulation of oxidized proteins is a hallmark of aging and a number of aging
      diseases. Oxidation can impair protein function as the proteins are unfolded
      leading to an increase of protein hydrophobicity and often resulting in the
      formation of toxic aggregates. The yeast Saccharomyces cerevisiae has been used
      as a eukaryotic model system to analyze the molecular mechanisms of oxidative
      stress protection. This paper reviews how the identification in yeast of specific
      damaged proteins has provided new insights into mechanisms of cytotoxicity and
      highlights the role of repair and degradative processes, including
      vacuolar/lysosomal and proteasomal proteolysis, in housekeeping after protein
      oxidative damage.

PMID- 17505969
TI  - Zinc deficiency in neuronal biology.
AB  - Adverse nutritional and environmental conditions during early development can
      irreversibly affect the nervous system. Zinc (Zn) deficiency associated with
      inadequate Zn intake and undernutrition is frequent throughout the world.
      Increasing evidence indicates that developmental Zn deficiency can lead to
      alterations in neonate and infant behavior, cognitive and motor performance that
      persist into adulthood. This review will address current knowledge on the events
      that are triggered in neuronal cells when Zn availability decreases and discuss
      their consequences on neuronal function and development. In neuronal cells, Zn
      deficiency induces oxidative stress, alters the normal structure and dynamics of
      the cytoskeleton, affects the modulation of transcription factors AP-1, NF-betaB
      and NFAT and induces a decreased cell proliferation and increased apoptotic
      death. Thus, these closely associated events can affect neuronal function and
      critical developmental events (neuronal proliferation, differentiation,
      plasticity and survival) when Zn availability decreases.

PMID- 17505970
TI  - Plant polyphenols: how to translate their in vitro antioxidant actions to in vivo
      conditions.
AB  - Epidemiological evidence demonstrates that diets rich in fruit and vegetables
      promote health, and attenuate, or delay, the onset of various diseases, including
      cardiovascular disease, diabetes, certain cancers, and several other age-related
      degenerative disorders. The chemical components and the physiological and
      molecular mechanisms by which fruit and vegetables reduce the risk for these
      pathophysiological conditions are matters of intense investigation. Regarding
      plant components, polyphenols are a group of phytochemicals that are gaining
      acceptance as responsible for the health benefits offered by fruit and
      vegetables. Because of their chemical structure, plant polyphenols are able to
      scavenge free radicals and inactivate other pro-oxidants. The connection of these
      chemical properties to a physiological antioxidant action has triggered extensive
      research aimed to relate the consumption of plant polyphenols with human health.
      Although significant progress has been made, there are still some critical areas
      that need to be elucidated to arrive at definitive conclusions on the mechanisms
      linking plant polyphenol consumption, reduction in oxidative damage, and health
      improvement. Some of these topics will be discussed in this review of alternative
      molecular mechanisms, based on polyphenol-membranes and polyphenol-proteins
      interactions that develop in an antioxidant protection but are not directly
      related to free radical scavenging or metal chelating.

PMID- 17505971
TI  - Synaptotoxicity in Alzheimer's disease: the Wnt signaling pathway as a molecular
      target.
AB  - Recent evidence supports a role of the Wnt pathway in neurodegenerative disorders
      such as Alzheimer's disease (AD). A relationship between amyloid-beta-peptide
      (Abeta)-induced neurotoxicity and a decrease in the cytoplasmatic levels of beta
      catenin has been proposed. Also, the inhibition of glycogen synthase kinase (GSK
      3beta), a central modulator of the pathway, protects rat hippocampal neurons from
      Abeta-induced damage. Interestingly, during the progression of AD, it has been
      described that active GSK-3beta is found in neuronal cell bodies and neurites, co
      localizing with pre-neurofibrillary tangles observed in disease brains. Since
      Abeta oligomers are associated with the post-synaptic region and we have found
      that the non-canonical Wnt signaling modulates PSD-95 and glutamate receptors, we
      propose that the synaptic target for Abeta oligomers in AD is the postsynaptic
      region and at the molecular level is the non-canonical Wnt signaling pathway.
      Altogether, our evidence suggests that a sustained loss of Wnt signaling function
      may be involved in the Abeta-dependent neurodegeneration observed in AD brains
      and that the activation of this signaling pathway could be of therapeutic
      interest in AD.

PMID- 17505972
TI  - Biological hydroperoxides and singlet molecular oxygen generation.
AB  - The decomposition of lipid hydroperoxides (LOOH) into peroxyl radicals is a
      potential source of singlet molecular oxygen ((1)O(2)) in biological systems.
      Recently, we have clearly demonstrated the generation of (1)O(2) in the reaction
      of lipid hydroperoxides with biologically important oxidants such as metal ions,
      peroxynitrite and hypochlorous acid. The approach used to unequivocally
      demonstrate the generation of (1)O(2) in these reactions was the use of an
      isotopic labeled hydroperoxide, the (18)O-labeled linoleic acid hydroperoxide,
      the detection of labeled compounds by HPLC coupled to tandem mass spectrometry
      (HPLC-MS/MS) and the direct spectroscopic detection and characterization of
      (1)O(2) light emission. Using this approach we have observed the formation of
      (18)O-labeled (1)O(2) by chemical trapping of (1)O(2) with anthracene derivatives
      and detection of the corresponding labeled endoperoxide by HPLC-MS/MS. The
      generation of (1)O(2) was also demonstrated by direct spectral characterization
      of (1)O(2) monomol light emission in the near-infrared region (lambda = 1270 nm).
      In summary, our studies demonstrated that LOOH can originate (1)O(2). The
      experimental evidences indicate that (1)O(2) is generated at a yield close to 10%
      by the Russell mechanism, where a linear tetraoxide intermediate is formed in the
      combination of two peroxyl radicals. In addition to LOOH, other biological
      hydroperoxides, including hydroperoxides formed in proteins and nucleic acids,
      may also participate in reactions leading to the generation (1)O(2). This
      hypothesis is currently being investigated in our laboratory.

PMID- 17505973
TI  - Soluble protein oligomers as emerging toxins in Alzheimer's and other amyloid
      diseases.
AB  - Amyloid diseases are a group of degenerative disorders characterized by
      cell/tissue damage caused by toxic protein aggregates. Abnormal production,
      processing and/or clearance of misfolded proteins or peptides may lead to their
      accumulation and to the formation of amyloid aggregates. Early histopathological
      investigation of affected organs in different amyloid diseases revealed the
      ubiquitous presence of fibrillar protein aggregates forming large deposits known
      as amyloid plaques. Further in vitro biochemical and cell biology studies, as
      well as studies using transgenic animal models, provided strong support to what
      initially seemed to be a solid concept, namely that amyloid fibrils played
      crucial roles in amyloid pathogenesis. However, recent studies describing tissue
      specific accumulation of soluble protein oligomers and their strong impact on
      cell function have challenged the fibril hypothesis and led to the emergence of a
      new view: Fibrils are not the only toxins derived from amyloidogenic proteins
      and, quite possibly, not the most important ones with respect to disease
      etiology. Here, we review some of the recent findings and concepts in this
      rapidly developing field, with emphasis on the involvement of soluble oligomers
      of the amyloid-beta peptide in the pathogenesis of Alzheimer's disease. Recent
      studies suggesting that soluble oligomers from different proteins may share
      common mechanisms of cytotoxicity are also discussed. Increased understanding of
      the cellular toxic mechanisms triggered by protein oligomers may lead to the
      development of rational, effective treatments for amyloid disorders.

PMID- 17505974
TI  - Etiology of three recent diseases of citrus in Sao Paulo State: sudden death,
      variegated chlorosis and huanglongbing.
AB  - The state of Sao Paulo (SSP) is the first sweet orange growing region in the
      world. Yet, the SSP citrus industry has been, and still is, under constant attack
      from various diseases. In the 1940s, tristeza-quick decline (T-QD) was
      responsible for the death of 9 million trees in SSP. The causal agent was a new
      virus, citrus tristeza virus (CTV). The virus was efficiently spread by aphid
      vectors, and killed most of the trees grafted on sour orange rootstock. Control
      of the disease resided in replacing sour orange by alternative rootstocks giving
      tolerant combinations with scions such as sweet orange. Because of its drought
      resistance, Rangpur lime became the favourite alternative rootstock, and, by
      1995, 85% of the SSP sweet orange trees were grafted on this rootstock.
      Therefore, when in 1999, many trees grafted on Rangpur lime started to decline
      and suddenly died, the spectre of T-QD seemed to hang over SSP again. By 2003,
      the total number of dead or affected trees was estimated to be over one million.
      The new disease, citrus sudden death (CSD), resembles T-QD in several aspects.
      The two diseases have almost the same symptoms, they spread in time and space in
      a manner strikingly similar, and the pathological anatomy of the bark at the bud
      union is alike. Transmission of the CSD agent by graft-inoculation has been
      obtained with budwood inoculum taken not only on CSD-affected trees (grafted on
      Rangpur lime), but also on symptomless trees (grafted on Cleopatra mandarin) from
      the same citrus block. This result shows that symptomless trees on Cleopatra
      mandarin are tolerant to the CSD agent. Trees on rootstocks such as Sunki
      mandarin or Swingle citrumelo are also tolerant. Thus, in the CSD-affected
      region, control consists in replacing Rangpur lime with compatible rootstocks, or
      in approach-grafting compatible rootstock seedlings to the scions of trees on
      Rangpur lime (inarching). More than 5 million trees have been inarched in this
      way. A new disease of sweet orange, citrus variegated chlorosis (CVC), was
      observed in 1987 in the Triangulo Mineiro of Minas Gerais State and the northern
      and north-eastern parts of SSP. By 2000, the disease affected already 34% of the
      200 million sweet orange trees in SSP. By 2005, the percentage had increased to
      43%, and CVC was present in all citrus growing regions of Brazil. Electron
      microscopy showed that xylem-limited bacteria were present in all symptomatic
      sweet orange leaves and fruit tissues tested, but not in similar materials from
      healthy, symptomless trees. Bacteria were consistently cultured from twigs of CVC
      affected sweet orange trees but not from twigs of healthy trees. Serological
      analyses showed the CVC bacterium to be a strain of Xylella fastidiosa. The
      disease could be reproduced and Koch's postulates fulfilled, by mechanically
      inoculating a pure culture of X. fastidiosa isolate 8.1.b into sweet orange
      seedlings. The genome of a CVC strain of X. fastidiosa was sequenced in SSP in
      the frame of a project supported by FAPESP and Fundecitrus. X. fastidiosa is the
      first plant pathogenic bacterium, the genome of which has been sequenced. Until
      recently, America was free of huanglongbing (HLB), but in March 2004 and August
      2005, symptoms of the disease were recognized, respectively in the State of Sao
      Paulo (SSP) and in Florida, USA. HLB was known in China since 1870 and in South
      Africa since 1928. Because of its destructiveness and its rapid spread by
      efficient psyllid insect-vectors, HLB is probably the most serious citrus
      disease. HLB is caused by a phloem sieve tube-restricted Gram negative bacterium,
      not yet available in culture. In the 1990s, the bacterium was characterized by
      molecular techniques as a member of the alpha proteobacteria designated
      Candidatus Liberibacter africanus for the disease in Africa, and Candidatus
      Liberibacter asiaticus for HLB in Asia. In SSP, Ca. L. asiaticus is also present,
      but most of the trees are infected with a new species, Candidatus Liberibacter
      americanus.

PMID- 17505975
TI  - Stress-inducible flavodoxin from photosynthetic microorganisms. The mystery of
      flavodoxin loss from the plant genome.
AB  - Flavodoxins (Flds) are mobile electron carriers containing flavin mononucleotide
      as the prosthetic group. They are isofunctional with the ubiquitous electron
      shuttle ferredoxin (Fd), mediating essentially the same redox processes among a
      promiscuous lot of donors and acceptors. While Fds are distributed throughout all
      kingdoms from prokaryotes to animals, Flds are only found in some bacteria and
      oceanic algae, in which they are induced to replace Fd functions under conditions
      of iron starvation and environmental stress that cause Fd decline. They thus play
      a key adaptive role in photosynthetic microorganisms, allowing survival and
      reproduction under adverse situations. The Fld gene disappeared from the plant
      genome somewhere between the green algal ancestor and the first terrestrial
      plants, and the advantages of this adaptive resource were irreversibly lost.
      However, reintroduction of a cyanobacterial Fld gene in the chloroplasts of
      transgenic tobacco resulted in remarkably enhanced tolerance to iron starvation
      and abiotic stress, indicating that the compensatory functions of Fld were still
      valuable in higher plants. A hypothesis is formulated to explain why Fld, in
      spite of its proven advantage, was lost from the plant genetic pool. The
      contention is based on two tenets: (i) iron availability was the major imperative
      for Fld conservation and adaptive value, and (ii) photosynthetic eukaryotes
      followed a succession of ecological adaptations, from the open oceans to coastal
      regions, and from there to the firm land, facing very different scenarios with
      respect to iron abundance and accessibility.

PMID- 17505977
TI  - NeuroAIDS in Brazil.
AB  - Brazil has the largest number of HIV cases of any single country in Latin America
      - over 600,000. Recently, investigators have begun to characterize the extent of
      neurological morbidity due to HIV in this country. During 2005 and 2006, the U.S.
      National Institute of Mental Health cosponsored two meetings of experts aimed at
      summarizing existing knowledge of HIV and its neurological complications in
      Brazil. Topics addressed ranged from clinical neurobehavioral aspects to
      molecular biology. Experts attending the meeting considered fruitful directions
      for future research.

PMID- 17505978
TI  - Silencing the PTEN gene is protective against neuronal death induced by human
      immunodeficiency virus type 1 Tat.
AB  - Neurons are targets of toxicity induced by the human immunodeficiency virus (HIV)
      1 protein Tat (transactivator of transcription). Exposure to Tat increases
      [Ca(2+)](i) in striatal neurons and activates multiple cell death pathways. In
      earlier studies the authors showed that Tat activated both caspase-3 and
      endonuclease-G, a caspase-independent effector of apoptosis, and that Tat-induced
      neurotoxicity was not attenuated by a caspase-3 inhibitor. Because Tat activates
      multiple, parallel death pathways, the authors attempted to reduce Tat-induced
      neurotoxicity by manipulating signaling pathways upstream of mitochondrial
      apoptotic events. PTEN (phosphatase and tensin homolog deleted on chromosome 10),
      a negative regulator of Akt/PKB (protein kinase B) phosphorylation, was chosen as
      a target for silencing. Akt/PKB activity directs multiple downstream pathways
      mediated by GSK3beta, BAD, forkhead transcription factors, nuclear factor kappa B
      (NFkappaB), and others, in a manner that promotes proliferation and survival.
      Striatal neurons were nucleofected with short interfering RNA (siRNA) vectors
      targeting PTEN, or a negative-control siRNA. Although Tat(1-86) significantly
      increased the death of neurons transfected with control construct by 72 h, PTEN
      silenced neurons were completely protected. These findings indicate that Akt is a
      critical intermediary in the direct neurotoxicity induced by HIV-1 Tat, and
      identify Akt regulation as a possible therapeutic strategy for Tat-induced
      neurotoxicity in HIV encephalitis (HIVE).

PMID- 17505979
TI  - Proteomic profiling reveals that rabies virus infection results in differential
      expression of host proteins involved in ion homeostasis and synaptic physiology
      in the central nervous system.
AB  - To understand how rabies virus (RV) infection results in neuronal dysfunction,
      the authors employed proteomics technology to profile host responses to RV
      infection. In mice infected with wild-type (wt) RV, the expression of proteins
      involved in ion homeostasis was altered. H(+) ATPase and Na(+)/K(+) ATPase were
      up-regulated whereas Ca(2+) ATPase was down-regulated, which resulted in
      reduction of the intracellular Na(+) and Ca(2+) concentrations. Furthermore,
      infection with wt RV resulted in down-regulation of soluble NSF attachment
      receptor proteins (SNAREs) such as alpha-synaptosome-associated protein (SNAP),
      tripartite motif-containing 9 (TRIM9), syntaxin, and pallidin, all of which are
      involved in docking and fusion of synaptic vesicles to and with presynaptic
      membrane. As a consequence, accumulation of synaptic vesicles was observed in the
      presynapses of mice infected with wt RV. These data demonstrate that infection
      with wt RV results in alteration of host protein expression, particularly those
      involved in ion homeostasis and docking and fusion of synaptic vesicles to
      presynaptic membrane, which may lead to neuronal dysfunction. On the other hand,
      attenuated RV up-regulated the expression of proteins involved in the induction
      of apoptosis, explaining why apoptosis is observed only in cells or animals
      infected with attenuated RV in previous studies.

PMID- 17505980
TI  - Effects of G207, a conditionally replication-competent oncolytic herpes simplex
      virus, on the developing mammalian brain.
AB  - Viral oncolytic therapy for malignant brain tumors involves local intratumoral
      delivery of a genetically engineered virus with tumor cell-specific lytic
      activity. Promising preliminary results have been achieved in preclinical models
      with G207, a replication-competent herpes simplex virus type 1 constructed with
      multiple directed mutations. Although the safety of G207 has been demonstrated in
      adults, application of viral oncolytic therapy to children with brain tumors has
      been delayed because of previous lack of data concerning the impact of a
      replication-competent oncolytic virus on the developing mammalian brain. In this
      study there was no significant difference in long-term physical development,
      cognitive performance, or exploratory behaviors between mice that received
      intracerebral inoculation of G207 or control saline at 4 days of age. However,
      histological examination and magnetic resonance imaging revealed frequent
      unilateral ventriculomegaly ipsilateral to the site of injection in only the G207
      group. These results suggest that although it is unlikely that G207 will have
      significant adverse effects on neurodevelopmental outcomes of pediatric patients
      with brain tumors, an initial study of G207 in children should exclude those
      patients with tumors in or near the ventricular system as well as patients less
      than 2 years of age. Furthermore, patients in such a study will need to be
      closely monitored for the development of hydrocephalus.

PMID- 17505981
TI  - West Nile virus encephalitis: sequential histopathological and immunological
      events in a murine model of infection.
AB  - West Nile virus (WNV) has emerged as an important cause of encephalitis in humans
      and horses in North America. Although there is significant knowledge about the
      pathogenesis of disease caused by this flavivirus and about the immunity against
      it, no reports exist describing the sequence of pathological changes and their
      correlation to the immune response in the brain following infection with WNV. In
      this report the authors describe the major histopathological changes, as well as
      changes in cytokine and chemokine expression, in brains from WNV-infected C57Bl/6
      mice. During the course of infection skin, spleen and kidney were all sites of
      WNV replication before virus reached the brain. In brain, increased expression of
      the chemokines monocyte chemoattractant protein (MCP)-5 (CCL12), interferon gamma
      inducible protein 10 (IP-10; CXCL10), and monokine induced by gamma interferon
      (MIG; CXCL9) preceded the expression of interferon gamma (IFN-gamma) and tumor
      necrosis factor alpha (TNF-alpha), which have previously been considered to be
      key early cytokines in the pathogenesis and immune response of WNV encephalitis.
      These results suggest that the chemokines MCP-5, IP-10, and MIG are important
      triggers of inflammation in brain due to their early up-regulation following WNV
      infection.

PMID- 17505982
TI  - A protein encoded by the bovine herpesvirus 1 open reading frame E gene induces
      neurite-like morphological changes in mouse neuroblastoma cells and is expressed
      in trigeminal ganglionic neurons.
AB  - Bovine herpes virus 1 (BHV-1), like other alpha-herpesvirinae subfamily members,
      establishes latency in sensory neurons. Periodically BHV-1 reactivates from
      latency, resulting in virus shedding and spread to uninfected cattle. Although
      reactivation from latency does not usually lead to recurrent disease, the latency
      reactivation cycle is crucial for virus transmission. The latency-related (LR)
      RNA is abundantly expressed during latency, and expression of a LR encoded
      protein is necessary for dexamethasone-induced reactivation from latency in
      cattle. Within LR promoter sequences, a small open reading frame (ORF) was
      identified (ORF-E) that is antisense to the LR-RNA, and downstream of the bICP0
      gene. ORF-E transcription is consistently detected in trigeminal ganglia (TG) of
      latently infected calves, suggesting ORF-E expression plays a role in the latency
      reactivation cycle. Polyclonal antiserum directed against an ORF-E peptide or the
      entire ORF-E protein specifically recognizes the nucleus of sensory neurons in TG
      of latently infected calves. The ORF-E peptide-specific antiserum also recognizes
      a protein when mouse neuroblastoma cells (neuro-2A) are transfected with an ORF-E
      expression construct. In contrast to the growth inhibiting properties of the LR
      gene, stably transfected ORF-E-expressing cells were obtained. Neuro-2A cells
      stably transfected with a plasmid expressing ORF-E induced morphological changes
      that resembled neurite-like projections. In contrast, neurite-like projections
      were not observed following transfection of neuro-2A cells with an empty vector.
      These studies suggest that a protein encoded by ORF-E has the potential to alter
      the physiology or metabolism of neuronal cell types, which may be important for
      long-term latency.

PMID- 17505983
TI  - Effects of human immunodeficiency virus and methamphetamine on cerebral
      metabolites measured with magnetic resonance spectroscopy.
AB  - Human immunodeficiency virus (HIV) and methamphetamine (METH) use disorders are
      associated with cerebral dysfunction. To determine whether these effects were
      evident on in vivo neuroimaging, quantitative, single voxel magnetic resonance
      (MR) spectroscopy was used to assess frontal white matter, frontal gray matter,
      and basal ganglia in 40 HIV+/METH+, 66 HIV+/METH-, 48 HIV-/METH+, and 51 HIV
      /METH- participants. HIV was associated with lower N-acetylaspartate (NAA) in
      frontal white and frontal gray matter but METH was not associated with cerebral
      metabolite differences in any region. Among HIV+ individuals, lower CD4 counts
      and higher plasma HIV viral loads were associated with lower NAA in frontal gray
      matter and basal ganglia. The relationship between detectable plasma HIV viral
      load and NAA in frontal white matter was significantly stronger in the HIV+/METH+
      group, compared to HIV+/METH-. Higher detectable plasma HIV viral load was
      significantly associated with higher myo-inositol (MI) in frontal white and gray
      matter for HIV+/METH+, but not HIV+/METH-. For the HIV-/METH+ group, lifetime
      duration of METH use was associated with higher choline levels in frontal gray
      matter and higher MI levels in basal ganglia. Our findings are consistent with
      significant disruption of neuronal integrity in the frontal lobes of HIV-infected
      individuals. Although METH was not associated with cerebral metabolite levels,
      other findings suggested that METH use did affect the brain. For example, the
      relationship between detectable plasma HIV viral load and NAA levels was limited
      to HIV+/METH+ individuals. This evidence indicates when HIV is poorly suppressed,
      METH may modify the effects of the virus on neuronal integrity.

PMID- 17505984
TI  - Nucleoside reverse transcriptase inhibitors and human immunodeficiency virus
      proteins cause axonal injury in human dorsal root ganglia cultures.
AB  - Distal symmetric polyneuropathy (DSP) has emerged as the most common complication
      of human immunodeficiency virus (HIV) infection, which is associated with
      neuronal injury in the dorsal root ganglion (DRG). With the advent of highly
      active antiretroviral therapy, especially nucleoside analogs, patients are living
      longer. Some of the antiretroviral drugs used to treat HIV infection have been
      associated with neuropathies. The pathogenesis of these neuropathies remains
      poorly understood. Utilizing a human fetal DRG model of predominantly nociceptive
      fibers, the authors investigated the effects of HIV gp120 and Tat(1-72), alone or
      in combination with nucleoside analogs on both morphological and ultra-structural
      changes in DRG neurons. Nucleoside analogs and HIV proteins both caused a
      significant decrease in the mean axonal length. However, ddI was the most potent,
      followed by ddC, d4T, and AZT. Despite the combined exposure to toxic dosages of
      HIV proteins and nucleoside analogs, there appeared to be a ceiling effect on the
      amount of axonal retraction, indicating that the proximal and distal axon are
      differentially regulated. In conclusion, both HIV proteins and nucleoside reverse
      transcriptase inhibitors (NRTIs) cause axonal damage by inducing mitochondrial
      injury and rearrangement of microtubules.

PMID- 17505985
TI  - Ceftriaxone protects against the neurotoxicity of human immunodeficiency virus
      proteins.
AB  - Human immunodeficiency virus (HIV) proteins Tat and gp120 have been implicated in
      the pathogenesis of HIV dementia by various mechanisms, including down-regulation
      of excitatory amino acid transporter-2 (EAAT2), which is responsible for
      inactivation of synaptic glutamate. Recent work indicates that beta-lactam
      antibiotics are potent stimulators of EAAT2 expression. The authors treated mixed
      human fetal neuronal cultures with recombinant gp120 or Tat, in the presence or
      absence of ceftriaxone, and determined neurotoxicity by measuring mitochondrial
      membrane potential and neuronal cell death. Ceftriaxone produced dose-dependent
      attenuation of the neurotoxicity and neuronal cell death caused by both viral
      proteins. This study demonstrates that this class of drugs may have therapeutic
      efficacy in HIV dementia.

PMID- 17505987
TI  - Antibiotic prophylaxis: an ongoing controversy in the treatment of severe acute
      pancreatitis.

PMID- 17505986
TI  - Brain-derived human immunodeficiency virus-1 Tat exerts differential effects on
      LTR transactivation and neuroimmune activation.
AB  - Molecular diversity within brain-derived HIV-1 sequences is highly variable
      depending on the individual gene examined and the neurological status of the
      patient. Herein, we examined different brain-derived human immunodeficiency virus
      (HIV)-1 tat sequences in terms of their effects on LTR transactivation and host
      gene induction in neural cells. Astrocytic and monocytoid cells co-transfected
      with prototypic tat clones derived from non-demented (ND) (n = 3) and demented
      (HAD) (n = 3) AIDS patients and different HIV-LTR constructs revealed that LTR
      transactivation mediated by tat clones derived from HAD patients was decreased (p
      < 0.05). A Tat-derived peptide containing the amino acid 24-38 domain from a ND
      clone caused down-regulation of the LTR transactivation (p < 0.05) in contrast to
      peptides from other Tat regions derived from HAD and ND tat clones. Both brain
      derived HAD and ND tat constructs were able to induce the host immune genes, MCP
      1 and IL-1beta. Microarray analysis revealed several host genes were selectively
      upregulated by a HAD-derived tat clone including an enzyme mediating heparan
      sulphate synthesis, HS3ST3B1 (p < 0.05), which was also found to be increased in
      the brains of patients with HAD. Expression of the pro-apoptotic gene, PDCD7, was
      reduced in cells transfected with the HAD-derived tat clone and moreover, this
      gene was also suppressed in monocytoid cells infected with a neurotropic HIV-1
      strain. Thus, mutations within the HIV-1 tat gene may exert pathogenic effects
      contributing to the development of HAD, which are independent of its effects on
      LTR transactivation.

PMID- 17505988
TI  - Hereditary iron and copper deposition: diagnostics, pathogenesis and
      therapeutics.
AB  - Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's
      disease) are autosomal recessive metabolic disease characterized by progressive
      liver pathology and subsequent involvement of various other organs. The
      prevalence of primary haemochromatosis is approximately 0.5%, about 200 times
      higher than the prevalence of Wilson's disease. The two diseases are
      characterized by homozygous occurrences of mutations in the HFE gene on
      chromosome 6 (primary haemochromatosis) and the ATP7B gene on chromosome 13
      (Wilson's disease). Unlike most other inherited conditions, these diseases can be
      successfully treated, emphasizing the importance of early diagnosis. Serum
      ferritin values, transferrin saturation and genetic analysis are used when
      diagnosing haemochromatosis. The diagnostics of Wilson's disease depends on the
      use of urinary copper values, serum ceruloplasmin and liver biopsy. If untreated,
      both of these genetic diseases result in rapidly progressing multiorgan damage
      and early death. The key treatment for haemochromatosis is phlebotomy, for
      Wilson's disease chelation or Zn treatment. Although the present treatments
      considerably improve the prognosis of patients, they may be inadequate in
      patients diagnosed so late that extensive body deposits of metal have been
      developed. The main research needs in this field are to further clarify molecular
      mechanisms of disease progression and to develop new chelators that are more
      effective and less toxic than those presently available.

PMID- 17505989
TI  - Conclusions from the histological diagnosis of low-grade intraepithelial
      neoplasia in Barrett's oesophagus.
AB  - OBJECTIVE: It is well known that low-grade intraepithelial neoplasia (LGIN) in
      Barrett's oesophagus (BE) might progress to high-grade intraepithelial neoplasia
      (HGIN) or carcinoma. Since accurate diagnosis of LGIN is difficult, general
      pathologists are frequently uncertain about the diagnosis of LGIN and its follow
      up risks. The purpose of this study was to analyse the divergence between the
      diagnoses of general and specialized gastrointestinal pathologists. MATERIAL AND
      METHODS: Fifty consecutive patients with a previous diagnosis of LGIN in BE, made
      by a general pathologist, were included in our study. The histopathological
      slides of every patient were reassessed in a blinded fashion by two specialized
      gastrointestinal (GI) pathologists. Inter-observer variability was calculated
      using kappa statistics. RESULTS: LGIN was confirmed by specialized pathologists
      in only 25/50 patients (50%). Twenty-one patients (42%) had Barrett's metaplasia
      without intraepithelial neoplasia and in 4 patients (8%) HGIN or Barrett's
      carcinoma (BC) was revealed. Inter-observer agreement between the general and
      specialized pathologists for the diagnosis of LGIN was poor (kappa = - 0.17) and
      good between both of the specialized pathologists (kappa = 0.69). Patients with
      HGIN/BC were treated by endoscopic resection or surgery. In patients with LGIN,
      ablative therapy was performed. Complete response was achieved in 25 patients,
      but 3 patients developed HGIN and 1 patient developed BC after 10+/-3.6 months.
      CONCLUSIONS: BE with LGIN is difficult to diagnose. Inter-observer variability is
      unacceptable between general and specialized pathologists and therefore when
      diagnosing LGIN a second opinion should always be sought by a specialized GI
      pathologist. Ablation therapy seems to be effective in patients with LGIN, but
      follow-up endoscopies are necessary to detect metachronous neoplasia.

PMID- 17505990
TI  - Can famotidine and omeprazole be combined on a once-daily basis?
AB  - OBJECTIVE: Prompt and long-standing acid control following once-daily
      administration of antisecretory drugs is desirable. The objective of this study
      was to determine whether co-administration of a well-characterized H2-receptor
      antagonist, famotidine, can be combined with the proton-pump inhibitor
      omeprazole. MATERIAL AND METHODS: Intragastric 24-h pH-metry was performed in
      healthy, Helicobacter pylori-negative volunteers on day 1 and after 8 days of
      daily administration of 20 mg omeprazole, 10 mg famotidine, or a combination of
      these in a three-way crossover design. RESULTS: A combination of famotidine and
      omeprazole raised the gastric pH level to >4 in less than 1 h. The percentage of
      daytime with pH > 4 on day 1 was significantly higher with the combination of
      omeprazole and famotidine (median: 37%) than that with omeprazole alone (22%; p <
      0.05). On day 8, daytime intragastric pH > 4 following treatment with omeprazole
      (median: 55%) or a combination of omeprazole and famotidine (61%) was superior (p
      < 0.05) to that with famotidine (21%). On day 1 treatment with both famotidine
      and the combination (famotidine and omeprazole) showed a significantly shorter
      time to reach a pH of 4 (medians: 93 and 63 min, respectively) compared with
      treatment with omeprazole alone (173 min; p < 0.05). CONCLUSIONS: Compared with
      treatment with omeprazole alone, on day 1 famotidine and omeprazole in
      combination improved the duration of and time to reach intragastric pH > 4. With
      regard to duration with pH > 4, the combination therapy was superior to
      famotidine alone on day 8. The rapid acid control with an H2-receptor antagonist
      may be combined with the long-lasting antisecretory effect of a proton-pump
      inhibitor.

PMID- 17505991
TI  - Size of the peptic ulcer in Helicobacter pylori-positive patients: association
      with the clinical and histological characteristics.
AB  - OBJECTIVE: Based on a large trial of Helicobacter pylori-positive peptic ulcer
      patients, we studied whether the size of the ulcer, along with other clinical and
      histological characteristics, has any effect on healing. We also studied the
      clinical and endoscopic characteristics associated with size of the peptic ulcer.
      MATERIAL AND METHODS: A total of 333 consecutive patients with H. pylori
      infection and peptic ulcer were enrolled (mean age 54.8+/-12.7 years). Location
      of the ulcer was recorded by gastroscopy and the presence of H. pylori was
      assured by rapid urease test, histology and by serum H. pylori IgG and IgA
      antibody measurement. The diameter of the ulcer was measured by placing the
      opened biopsy forceps (7 mm) beside it. Biopsy specimens were examined in
      accordance with the Sydney system. RESULTS: Mean size of the peptic ulcer was
      13.2+/-8.3 in corpus, 11.3+/-5.3 in antrum, 13.8+/-7.8 in angulus, 9.5+/-5.3 in
      prepylorus and 9.2+/-4.7 mm in duodenum (duodenal versus gastric type; p<0.05).
      Average size of the ulcers was 9.4+/-5.3 mm in patients with Forrest III type and
      11.5+/-6.8 in other types (p<0.05). Patients who were >or=50 years of age,
      currently smoking, or who had corpus-predominant chronic gastritis or atrophic
      gastritis, had larger ulcers than others. Size of index ulcers, successful
      eradication of H. pylori and the presence of atrophic gastritis were independent
      factors for healing. The odds ratio was 11.5 (95% CI 3.3-40.5; p<0.01) for
      eradication of H. pylori, 3.5 (95% CI 1.1-11.2; p<0.05) for size of the index
      ulcer (<or=10 mm versus >10 mm) and 3.4 (95% CI 1.2-9.8; p<0.05) for atrophic
      gastritis versus no atrophy. CONCLUSIONS: Size of the peptic ulcer, successful H.
      pylori eradication and atrophic gastritis were independent factors for the
      healing of peptic ulcers. A number of clinical and endoscopic variables (age,
      current smoking, corpus-predominant gastritis, Forrest classification) were
      associated with size of the peptic ulcer in H. pylori-positive patients.

PMID- 17505992
TI  - Long-pulse gastric electrical stimulation at tachygastrial frequency reduces food
      intake by inhibiting proximal gastric tone.
AB  - OBJECTIVE: To investigate the effects of long pulse gastric electrical
      stimulation (GES) at a tachygastrial frequency on food intake, gastric tone and
      gastric myoelectrical activity (GMA). MATERIAL AND METHODS: Of twelve dogs
      implanted with electrodes and a gastric cannula, 6 underwent truncal vagotomy.
      Stimulus consisted of long pulses with a frequency of 9 cycles/min. Experiment
      one was performed in all dogs to test for food intake with or without GES.
      Experiment two on six normal dogs consisted of baseline, GES and recovery
      periods. Gastric volume and GMA were recorded. RESULTS: 1) GES reduced food
      intake in both normal (398.5+/-111.7 g versus 573.0+/-97.9 g; p<0.02) and
      vagotomized dogs (170.6+/-100.4 g versus 401.0+/-97.3 g; p<0.05). 2) Gastric
      volume was increased with stimulation from 168.4+/-17.7 ml to 301.1+/-34.1 ml
      (p<0.02 ANOVA) and maintained at 271.8+/-27.6 ml. 3) The percentages of normal
      slow waves before, during and after GES were 83.3+/-4.6%, 38.0+/-3.5% and 61.0+/
      12.5%, respectively (p=0.02 ANOVA). CONCLUSION: Long-pulse GES at tachygastrial
      frequency substantially reduces food intake, and is not mediated by the vagal
      pathway but attributed to relaxation of the stomach and impairment of intrinsic
      GMA.

PMID- 17505993
TI  - Functional characteristics of the porcine colonic epithelium following
      transportation stress and Salmonella infection.
AB  - OBJECTIVE: Stressful life events and infections contribute to gut disorders such
      as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We used a
      pig model to analyse whether this could be linked to altered mediator sensitivity
      of the epithelial lining. MATERIAL AND METHODS: Uninfected control pigs or pigs
      with subclinical Salmonella (S.) typhimurium DT 104 infection were killed either
      without (ConRest, InfRest) or with prior 8-h transportation (ConTrans, InfTrans).
      Short-circuit current (I(sc)), tissue conductance (G(t)) and release of mast cell
      mediators were monitored in isolated colonic epithelia mounted in Ussing
      chambers. Epithelia were exposed to histamine (100 microM, mucosally), substance
      P (SP; 1 microM, serosally), calcimycin A23187 (1 microM, serosally) and
      theophylline (10 mM, bilaterally). Transepithelial flux of histamine and colonic
      activities of histamine N-methyltransferase (HMT) and diamine oxidase (DAO) were
      determined. RESULTS: S. infection decreased baseline I(sc), G(t) and histamine
      fluxes, while transportation had no effect on these values. Mucosal histamine
      increased I(sc) only in ConTrans pigs. This was not associated with increased
      mucosal-to-serosal flux of histamine but with a 2-fold increased DAO activity.
      Serosal SP increased I(sc) only in transported animals, but the increase was six
      times higher in ConTrans versus InfTrans pigs. Effectiveness of SP was not
      dependent on the release of histamine or prostaglandin D2. A23187 and
      theophylline elicited increases in I(sc) that were not different between
      treatments. CONCLUSIONS: Transportation stress facilitates secretory responses of
      the colonic epithelium to SP and luminal histamine. This is suppressed by
      subclinical S. infection. Effects of S. infection on porcine colon resemble, in
      part, the known effects of an oral S. endotoxin application.

PMID- 17505994
TI  - Ethnic and socio-cultural specificities in Tunisia have no impact on the
      prevalence of anti-Saccharomyces cerevisiae antibodies in Crohn's disease
      patients, their relatives or associated clinical factors.
AB  - BACKGROUND: In Western Europe and the USA, the presence of anti-Saccharomyces
      cerevisiae antibodies (ASCAs) in Crohn's disease (CD) patients and their healthy
      relatives suggests that ASCAs may be influenced by genetic and/or environmental
      factors. OBJECTIVES: To assess the prevalence of ASCAs in Tunisian patients with
      CD or ulcerative colitis (UC), and unaffected family members, in relation to
      clinical phenotype. Patients and methods. Seventy-seven patients (39 CD, 38 UC),
      66 healthy relatives of CD patients, 16 relatives of UC patients and 70 healthy
      controls were studied. ASCAs were quantified with a new isotype-specific ELISA
      test involving an antigenic extract from S. cerevisiae strain W303 and by the
      original test which detects total immunoglobulins against S. cerevisiae Su1
      mannan. RESULTS: The specificity of the two tests was identical (91%). The
      isotype-specific ASCA W303 test was more sensitive than the ASCA Su1 test for
      immunoglobulin detection, but some CD patients were positive only with this
      latter test. A high percentage of patients with CD (72%) and their unaffected
      family members (35%) were ASCA-positive in contrast to UC patients (16%) and
      their relatives (0%) and controls (8.6%). ASCAs were shown to be independent of
      rural or urban living, disease activity, but were associated with ileal location.
      The antigen of S. cerevisiae strain W303 discriminated patients depending on age
      at onset or location of the disease. CONCLUSION: This study confirms the
      antigenic heterogeneity of S. cerevisiae strains in their ability to detect ASCA.
      It suggests that ASCAs are markers of immunoregulatory disturbance in CD,
      independently of ethnic/cultural differences between Europe, the USA and North
      Africa.

PMID- 17505996
TI  - Effects of a comprehensive lifestyle modification program on quality-of-life in
      patients with ulcerative colitis: a twelve-month follow-up.
AB  - OBJECTIVE: To analyze the effects of a comprehensive lifestyle modification
      program on health-related quality-of-life, psychological distress, and clinical
      parameters in patients with ulcerative colitis (UC) 3- and 12 months after
      completion of the program. MATERIAL AND METHODS: Sixty patients with UC in
      clinical remission or with low disease activity were randomly assigned to an
      intervention group or a usual-care control group. Comprehensive lifestyle
      modification consisted of a structured 60-h training program over a period of 10
      weeks which included stress management training, psychoeducational elements, and
      self-care strategies. Quality-of-life, psychological distress, and clinical
      disease activity were assessed with standardized questionnaires (Inflammatory
      Bowel Disease Questionnaire (IBDQ); the MOS Short-Form 36 (SF-36); the Brief
      Symptom Inventory (BSI), and the Colitis Activity Index (CAI)) at baseline, and 3
      months and 12 months after comprehensive lifestyle modification. RESULTS: Three
      months after comprehensive lifestyle modification, patients in the intervention
      group showed significantly greater improvement in the SF-36 scale physical
      function (p=0.0175), and a significantly greater reduction in anxiety scores,
      measured with the BSI (p=0.0294). Use of relaxation techniques was a significant
      predictor of improvement in the psychological sum score after 3 months of therapy
      (p=0.034). Though 80% of patients with an initial IBDQ score <170 in the
      intervention group showed an improvement of >16 points after 3 months, no
      significant effects of the intervention were found on the IBDQ scales, or on
      clinical disease parameters, including CAI scores, self-assessed disease
      activity, hospitalizations, or medical consultations. CONCLUSIONS: These results
      are consistent with possible short-term benefits of a comprehensive lifestyle
      modification program on some aspects of quality-of-life and emotional well-being,
      but no effects were discernable 12 months after completion of therapy.
      Comprehensive lifestyle modification had no effect on clinical disease variables.
      The generalizability of these data is limited because of the inclusion of
      patients with a relatively low disease activity who were interested in
      integrative medicine.

PMID- 17505995
TI  - ATP-binding cassette transporter ABCG2 (BCRP) and ABCB1 (MDR1) variants are not
      associated with disease susceptibility, disease phenotype response to medical
      therapy or need for surgeryin Hungarian patients with inflammatory bowel
      diseases.
AB  - OBJECTIVE: MDR1 (ABCB1), a member of the ATP-binding cassette (ABC) transporters,
      is an attractive candidate gene for the pathogenesis of inflammatory bowel
      diseases (IBD) and perhaps for response to therapy. Since limited data are
      available on MDR1 and ABCG2 polymorphisms in East European IBD patients, the aim
      of this study was to investigate ABCG2 and MDR1 variants and responses to medical
      therapy and/or disease phenotype in Hungarian patients. MATERIAL AND METHODS: A
      total of 414 unrelated IBD patients (Crohn's disease (CD): 265, age: 35.2+/-12.1
      years, duration: 8.7+/-7.6 years and ulcerative colitis (UC): 149, age: 44.4+/
      15.4 years, duration: 10.7+/-8.9 years) and 149 healthy subjects were
      investigated. ABCG2 G34A, C421A and MDR1 C3435T, G2677T/A single nucleotide
      polymorphisms (SNPs) were detected using real-time polymerase chain reaction
      (PCR). Detailed clinical phenotypes were determined by reviewing the medical
      charts. RESULTS: The frequency of the ABCG2 and MDR1 SNPs was not significantly
      different among IBD, CD, UC patients and controls. There was no difference in
      risk for steroid resistance in CD patients carrying variant ABCG2 (19.6% versus
      non-carriers 18.4%, p=NS) or MDR1 3435T (CC: 22.2% versus CT/TT: 17.6%) alleles.
      In addition, carriage of the variant allele was not associated with disease
      phenotype, presence of extra-intestinal manifestations, smoking, response to
      infliximab therapy or the need for surgery. In UC, the carriage of variant ABCG2
      alleles seemed to be preventive for arthritis (15.5% versus 31.7%, OR: 0.39, 95%
      CI: 0.16-0.98). CONCLUSIONS: MDR1 and ABCG2 SNPs were not associated with disease
      susceptibility or disease phenotype in Hungarian patients, and variant alleles
      did not predict the response to medical therapy or the need for surgery. Further
      studies are needed to clarify the association between the presence of ABCG2
      variants and arthritis in UC.

PMID- 17505997
TI  - Genotype-phenotype correlations in individuals with a founder mutation in the
      MLH1 gene and hereditary non-polyposis colorectal cancer.
AB  - OBJECTIVE: A unique mutation of the MLH1 gene was recently reported in six
      families living in a small area of Northern Italy. The mutation consists in the
      insertion of a T base between nucleotides 2269 and 2270 (2269-2270insT), causing
      the synthesis of an unstable polypeptide. The mutation was not reported by other
      investigators or outside this small geographic area, thus suggesting a possible
      founder effect. The main purpose of this investigation was to investigate whether
      patients (and families) with the 2260-2270insT mutation show relevant clinical
      differences when compared with individuals with other MLH1 or MSH2 gene
      alterations. MATERIAL AND METHODS: We identified hereditary non-polyposis
      colorectal cancer (HNPCC) families through the specialized colorectal cancer
      registry following a previously described multistep approach. In all, 58 HNPCC
      families were identified; of these, 38 were detected through the registry, and 20
      were referred from other areas in Italy. RESULTS: Small differences were found in
      the main clinical and pathologic features; however, tumour burden per family
      tended to be higher in kindred sharing the founder mutation; in addition,
      multiple primaries (four or five different tumours in some subjects) were
      significantly more frequent in patients with the 2269-2270insT than in
      individuals with MSH2, MLH1 gene mutations or sporadic colorectal neoplasms. No
      significant difference in prognosis was found between patients with the founder
      mutation and those with other MLH1 or MSH2 mutations. Regardless of the type of
      mutation, neoplasms of the colon-rectum, stomach and endometrium represented
      nearly 80% of the tumour burden in families with HNPCC. CONCLUSIONS: A proclivity
      to multiple tumours arising in the same subject and a higher tumour burden per
      family were the most relevant findings observed in affected patients with the
      founder mutation compared with other MLH1 or MSH2 mutations. In general, the
      results of the study underline the difficulty in discriminating between Lynch I
      and Lynch II syndromes on the basis of specific molecular changes.

PMID- 17505998
TI  - Predictive factors in pancreatic ductal adenocarcinoma: role of the inflammatory
      response.
AB  - OBJECTIVE: Pancreatic ductal adenocarcinoma is a highly lethal disease and most
      patients are not eligible for curable resection. Estimation of prognosis is
      essential in order to provide the best individual treatment for patients with
      pancreatic adenocarcinoma. Prediction of survival by current methods is limited,
      therefore the objective of this study was to determine possible prognostic
      factors identified at the time of diagnosis. MATERIAL AND METHODS: All 119
      consecutive patients with pancreatic ductal adenocarcinoma receiving palliative
      treatment at the Department of Surgery, Lund University Hospital from 1999
      through 2002 were reviewed retrospectively. Prognostic factors and interventions
      were analysed statistically. C-reactive protein (CRP) at the time of diagnosis
      was measured in 109 patients. RESULTS: The overall median survival was 4.4
      months. By means of a multivariate analysis it was shown that CRP (p<0.001) and
      tumour size (p=0.018) were independent predictors of survival. The median
      survival of patients with normal CRP at the time of diagnosis was 10.8 months
      versus 4.2 months for those with raised CRP levels (>or=5 mg/l; p<0.001).
      Chemotherapy was the only intervention associated with a longer survival time
      (p<0.001 versus no chemotherapy). CONCLUSIONS: The poor prognosis for patients
      with pancreatic ductal adenocarcinoma was confirmed. CRP proved to be a strong
      independent predictor of survival. Together with previous reported factors, CRP
      could serve as a potential tool to determine future treatment strategies for
      optimal individual palliation.

PMID- 17505999
TI  - Reduction in gastric cancer mortality by screening based on serum pepsinogen
      concentration: a case-control study.
AB  - OBJECTIVE: Pepsinogen testing is widely used in Japan as a method of screening
      for gastric cancer. To evaluate the efficacy of this method, a case-control study
      was conducted in a rural town in Hiroshima prefecture, Japan, where no previous
      pepsinogen testing had been performed. MATERIAL AND METHODS: Three age-and gender
      matched control subjects were randomly selected for each of 41 individuals who
      had died of gastric cancer. The three control subjects were selected from
      individuals who were living in the same area as the patient when gastric cancer
      was diagnosed. RESULTS: The odds ratios for death from gastric cancer among
      control subjects screened within 1 and 2 years before the individuals were
      diagnosed versus those not screened were 0.238 (95% confidence interval (CI):
      0.061-0.929), and 0.375 (95% CI: 0.155-0.905), respectively. CONCLUSIONS: The
      study results suggest that gastric cancer screening using the pepsinogen method
      may reduce mortality from gastric cancer.

PMID- 17506000
TI  - Treatment with anti-factor VIIa in acute pancreatitis in rats: blocking both
      coagulation and inflammation?
AB  - OBJECTIVE: Acute pancreatitis starts as an autodigestive process restricted to
      the pancreas and progresses to a systemic inflammation via cytokine release into
      the blood stream. Several inhibitors of the coagulation cascade, including active
      site-inactivated factor VIIa, have shown anti-inflammatory properties in other
      inflammatory models than acute pancreatitis. Free radical scavengers have proven
      useful in reducing the oxidative damage during hyperinflammatory conditions. The
      aim of this study was to investigate whether pretreatment with FVIIai would have
      any effect on the multiple organ dysfunction syndrome (MODS) in severe acute
      pancreatitis. MATERIAL AND METHODS: Experimental acute pancreatitis was induced
      by intraductal infusion of taurodeoxycholate in the pancreatic duct. The animals
      were pretreated with N-acetyl-cysteine and active-site-inactivated factor VIIa.
      Neutrophil infiltration in the lungs, ileum and colon was quantified by
      myeloperoxidase activity. Inflammatory markers, IL-6 and MIP-2, were measured
      using ELISA. RESULTS: Tissue infiltration of neutrophils in the lungs, ileum and
      colon significantly increased during acute pancreatitis as compared to sham
      operation. These levels were reduced by pretreatment with N-acetylcysteine and
      active-site-inactivated factor VIIa. Levels of interleukin-6 and macrophage
      inflammatory protein-2 increased significantly during acute pancreatitis.
      Pretreatment with NAC and FVIIai reduced these levels. CONCLUSIONS: Both N
      acetylcysteine and active-site-inactivated factor VIIa showed powerful anti
      inflammatory properties in experimental acute pancreatitis. As they exert their
      effects through different physiological mechanisms, they represent potential
      candidates for future multimodal treatment of acute pancreatitis.

PMID- 17506001
TI  - Early treatment of severe pancreatitis with imipenem: a prospective randomized
      clinical trial.
AB  - OBJECTIVE: The main causes of death in severe pancreatitis are multiorgan failure
      and septic complications. Prophylactic treatment with effective antibiotics is
      therefore a tempting therapeutic option. However, there could be side effects
      such as selection of resistant microbes and fungi. The aim of the present study
      was to compare the rate of infectious complications, interventions, days in the
      intensive care unit (ICU), morbidity and mortality in patients with severe
      pancreatitis randomized to prophylactic therapy with imipenem compared with those
      receiving no treatment at all. MATERIAL AND METHODS: Seventy-three patients with
      severe pancreatitis were included in a prospective, randomized, clinical study in
      seven Norwegian hospitals. The number of patients was limited to 73 because of
      slow patient accrual. Severe pancreatitis was defined as a C-reactive protein
      (CRP) level of >120 mg/l after 24 h or CRP >200 48 h after the start of symptoms.
      The patients were randomized to either early antibiotic treatment (imipenem 0.5 g
      x 3 for 5-7 days) (imipenem group) (n=36) or no antibiotics (control group)
      (n=37). RESULTS: The groups were similar in age, cause of pancreatitis, duration
      of symptoms and APACHE II score. Patients in the imipenem group experienced lower
      rates of complications (12 versus 22 patients) (p=0.035) and infections (5 versus
      16 patients) (p=0.009) than those in the control group. There was no difference
      in length of hospital stay (18 versus 22 days), need of intensive care (8 versus
      7 patients), need of acute interventions (10 versus 13), nor for surgery (3
      versus 3) or 30-day mortality rates (3 versus 4). CONCLUSIONS: The study,
      although underpowered, supports the use of early prophylactic treatment with
      imipenem in order to reduce the rate of septic complications in patients with
      severe pancreatitis.

PMID- 17506002
TI  - Colon carcinoma metastasis to the intrapancreatic tract of the common biliary
      duct: a first case report.
AB  - Jaundice, a common feature of advanced colon cancer, is usually due to liver
      parenchyma metastasis, but it can sometimes be caused by extrahepatic biliary
      obstruction. This rare event is related to metastasis to the lymph nodes placed
      behind the duodenum, along the choledochus or the vena porta, extrinsically
      compressing the common duct. Stenosis of the common bile duct secondary to
      parietal metastatic involvement is extremely rare. We report on a case of colon
      carcinoma metastasis to the intrapancreatic tract of the common bile duct, with a
      review of the literature.

PMID- 17506003
TI  - Post-renal transplantation Leser-Trelat sign associated with carcinoma of the
      gallbladder: a rare association.
AB  - The sign of Leser-Trelat represents the sudden appearance of multiple seborrheic
      keratoses in association with an underlying malignancy. The most common
      associated neoplasms belong to the gastrointestinal tract, mainly the stomach and
      colon. In the literature, there is only one case of gallbladder carcinoma
      associated with the Leser-Trelat sign. Thus, the hallmark of our patient is post
      renal transplant malignancy-associated Leser-Trelat, which has not been reported
      before. Here, we report on a 57-year-old man who presented with a sudden increase
      in the number and size of seborrheic keratoses, particularly on sun-exposed areas
      24 years after renal transplantation. The search for an underlying malignancy
      showed the presence of an adenocarcinoma of the gallbladder which had
      metastasized to the liver.

PMID- 17506004
TI  - Prevalence of liver fibrosis and cirrhosis in screening-detected C282Y homozygous
      subjects.

PMID- 17506005
TI  - First appearance of Crohn's disease following infliximab treatment for
      spondylarthropathy.

PMID- 17506006
TI  - Prevention by a decapeptide from durum wheat of in vitro gliadin peptide-induced
      apoptosis in small-bowel mucosa from coeliac patients.

PMID- 17506007
TI  - A novel frameshift mutation in the APC gene at exon 15 in familial adenomatous
      polyposis (FAP) with desmoid tumour.

PMID- 17506009
TI  - [Smoking behavior during pregnancy of women with type 1 or gestational diabetes].
AB  - BACKGROUND AND OBJECTIVE: Smoking and diabetes mellitus (DM) are both risk
      factors for complications during pregnancy and disorders in the newborn. Smoking
      behavior during pregnancy was investigated in German families where either the
      pregnant woman or her spouse had diabetes. The relationship between maternal
      smoking during pregnancy, her metabolic state and the child's birth weight was
      analysed. PATIENTS AND METHODS: Data on smoking behavior during pregnancy of
      women and their spouses were obtained by questionnaire. 2 498 families were
      included: 1,439 women and 1,010 men with type 1 diabetes (T1D) and 1,059 women
      and 1,488 men without T1D, deliveries having taken place between 1989 and 2005
      (no account was taken of the amount smoked or whether stopped during pregnancy).
      Also collected were data on 308 women with gestational diabetes (GDM), who
      delivered a baby between 1989 and 1997. RESULTS: Significantly more pregnant
      women with T1D and GDM smoked than pregnant women without diabetes (13.2% and
      15.2% vs 8.7%, p=0.001). Children of smoking pregnant women with T1D had a
      significantly lower birth weight than those of non-smoking pregnant women with
      T1D (median 54th percentile vs 71st percentile, p<0.001), although smoking
      pregnant women had a higher HbA (1c) than non-smoking pregnant women with T1D
      (median 6.1% vs 5.7%, p<0.001). The number of women and men who smoked during
      pregnancy declined between 1989 and 2005 (women: 17.5% vs. 8.9%, p=0.02, men:
      38.0% vs 24.7%, p<0.001). CONCLUSIONS: The lower birth weight of children of
      mothers who smoked demonstrates the detrimental consequences of smoking during
      pregnancy. Pregnant woman with diabetes are a high risk group that should be
      targeted with programmes that aim to stop smoking during pregnancy.

PMID- 17506010
TI  - [Pulmonary and cardiac recurrence of sarcoidosis in a heart transplant
      recipient].
AB  - HISTORY: A 38-year-old man underwent heart transplantation for end-stage heart
      failure as a result of sarcoid cardiomyopathy. Routine post-transplantation
      endomyocardial biopsies demonstrated no graft rejection. However, six months post
      transplantation, while on immunosuppressive medication, the patient noted a dry
      cough. INVESTIGATIONS: Cardiovascular magnetic resonance imaging (MRI) showed
      recurrent sarcoidosis in the transplanted heart, and bronchoscopy revealed
      granulomas consistent with pulmonary sarcoidosis. The chest radiograph revealed
      bilateral perihilar interstitial nodular infiltration. Whole blood analysis,
      coagulation and electrolyte parameters as well as inflammatory and enzyme values
      were within the normal range. TREATMENT AND COURSE: The patient was treated with
      an increased dosage of prednisone. Furthermore, the immunosuppression with
      cyclosporin and everolimus was replaced by cyclosporin and azathioprine. Regular
      pulmonary function tests were done in addition to the routine biopsy controls and
      the laboratory tests as well as electrocardiography, echocardiography and
      radiography. The patient has remained well at eighteen months after
      transplantation. CONCLUSIONS: For those patients who develop end-stage
      cardiomyopathy from sarcoidosis, heart transplantation is still the therapy of
      choice. The recurrence of sarcoidosis in a transplanted heart has been only very
      rarely reported in the literature. Once recurrence is diagnosed patients should
      be treated with an increased dosage of steroid in addition to standard
      immunosuppressives.

PMID- 17506011
TI  - [Trachea diverticulum with secretions].

PMID- 17506012
TI  - [Diagnosis and staging of lung cancer].
AB  - Despite medical advances lung cancer remains the leading cause of cancer deaths.
      Lung cancer is usually recognized late in its natural history and at presentation
      in 80 % unresectable. Smoking history is the most important risk factor. At
      present time, screening for lung cancer is not recommended. The only chance for
      cure is tumour resection in early stages, performed in about 20 % of all lung
      cancer cases. Histological subtypes are non-small cell lung cancer (NSCLC) (80 %
      of lung cancers) and 20 % small cell lung cancer (SCLC). TNM-staging has
      important influence on prognosis and therapy. After identification the tumour
      should be staged using the TNM system. Currently diagnosis and staging rely
      predominantly on chest radiography and computed tomography (CT) scanning.
      Positron emission tomography (PET) identifies the tumour by its metabolic
      activity and helps to find malignant nodal or systemic lesions. Flexible
      bronchoscopy is the key investigation in the diagnosis and staging of patients
      with suspected lung cancer. Endobronchial ultrasound guided transbronchial fine
      needle aspiration (TBNA) may be utilized to improve the bronchoscopic results in
      mediastinal staging. Internistic thoracoscopy or video assisted thoracoscopic
      surgery (VATS) may be used in malignant pleural effusions. Mediastinoscopy
      staging is the gold-standard for mediastinal staging.

PMID- 17506013
TI  - [Chlamydia trachomatis infections--a time for action?].
AB  - Infection with Chlamydia trachomatis is the most common sexually transmitted
      disease in the world. In women it mainly occurs before the age of 25 years, while
      in men it can still be diagnosed till the age of 35 years. In Western Europe the
      prevalence of a Chlamydia trachomatis infection has been estimated, according to
      WHO data, as between 2.7% (Italy) and 8.0% (Island). A general screening strategy
      is now being discussed in Germany. A non-diagnosed and non-treated Chlamydia
      trachomatis infection and the resulting health problems have not only severe
      consequences for the individual but also results in major epidemiological and
      socio-economic public health problems. This issue is not only of extreme
      importance in health policy, but has also a major impact in family policy,
      especially in view of the declining birth rates and the demographic changes.

PMID- 17506014
TI  - [Ascites paracentesis].

PMID- 17506016
TI  - [The central venous catheter. Approach to the subclavian vein].

PMID- 17506017
TI  - [The central venous catheter. Approach to the subclavian vein].

PMID- 17506018
TI  - [Comorbidity in attention deficit-/hyperactivity disorder (ADHD) - important
      issue for diagnostics and treatment].

PMID- 17506019
TI  - [Autism and ADHD - are there common traits?].
AB  - INTRODUCTION: Genetic, neuropsychological and psychopathological findings refer
      to a connection of autism and attention deficit/hyperactivity disorder (ADHD).
      Although the disorders represent different nosological diagnoses they partly
      include similar symptoms like hyperactivity, impulsivity and attention deficit
      disorder. METHODS: This paper gives an overview of genetic, morphological,
      neurophysiological and -psychological studies concerning ADHD and autism. In
      addition, results concerning pharmacotherapy and the development of both
      disorders in adulthood are described. RESULTS: With regard to genetics, common
      candidate regions are discussed. Under a morphological perspective, results on
      the one hand point out identical brain regions or functional systems but on the
      other hand underline that these regions are not equally affected. The
      morphological results could not be replicated on a neuropsychological basis. So
      far findings of studies which involved combined ADHD- and autistic samples lead
      to controversal results. CONCLUSION: At present, there exist only few studies
      which include the issue of attention disorders in autism and ADHD in a same
      sample. With regard to diagnosis and therapeutical interventions, further
      research concerning the etiology of both disorders is necessary.

PMID- 17506020
TI  - [Attention deficit-/hyperactivity disorder in adults].

PMID- 17506021
TI  - [Absinthe - history of dependence to thujone or to alcohol?].
AB  - The etiopathology of absinthe dependence was previously attributed to the effects
      of the wormwood constituent thujone. Current research proves otherwise. Foremost,
      it must be considered that the wormwood plant shows a very large variance in
      quantity of thujone (0 - 70 % in essential oil) dependent on chemo type and
      cultivation area. Thus, absinthe does not contain thujone in general.
      Experimental production of absinthes and analyses of vintage absinthes (1900 -
      1930) consistently showed that they contained only relatively low concentrations
      of thujone below today's maximum limits. Scientific literature contains no proof
      that historic absinthes may have contained thujone in concentrations able to
      produce toxic effects. The current state of research considers absinthism to be a
      type of alcoholism with thujone playing none or only a secondary role.

PMID- 17506022
TI  - [Thujon and absinthe--a historical misperception?].

PMID- 17506023
TI  - [Is German as the language of psychiatry not up to date?].

PMID- 17506024
TI  - Quantitative magnetic resonance imaging of articular cartilage in osteoarthritis.
AB  - Magnetic resonance imaging of articular cartilage has recently been recognized as
      a tool for the characterization of cartilage morphology, biochemistry and
      function. In this paper advancements in cartilage imaging, computation of
      cartilage volume and thickness, and measurement of relaxation times (T2 and
      T1Rho) are presented. In addition, the delayed uptake of Gadolinium DTPA as a
      marker of proteoglycan depletion is also reviewed. The cross-sectional and
      longitudinal studies using these imaging techniques show promise for cartilage
      assessment and for the study of osteoarthritis.

PMID- 17506025
TI  - Suicidality in middle aged and older patients with schizophrenia and depressive
      symptoms: relationship to functioning and Quality of Life.
AB  - BACKGROUND: Suicidality is a health concern in patients with schizophrenia. We
      examined the hypotheses: (1) Middle aged and older patients with schizophrenia,
      depressive symptoms and suicidality would exhibit worse quality of life and worse
      everyday functioning, social skills and medication management relative to those
      without suicidality; (2) higher levels of suicidality would be significantly
      associated with worse functioning, worse quality of life and older age. METHODS:
      We examined 146 outpatients with schizophrenia and depression. Patients were at
      least 40 years old and were diagnosed with schizophrenia or schizoaffective
      disorder and had two or more depressive symptoms based on DSM-IV criteria for
      major depression. We assessed suicidality with the Intersept Suicide Scale (ISS)
      and functioning with the UCSD Performance-based Skills Assessment (UPSA), Social
      Skills Performance Assessment (SSPA), and Medication Management Ability
      Assessment (MMAA). Quality of life was assessed with the Heinrichs Quality of
      Life Scale (QLS). RESULTS: The mean age of patients was 52.4+ 6.9 years. Subjects
      with suicidality (ISS scores > 0) had lower QLS scores compared to those without
      suicidality. However, there were no differences in UPSA, SSPA nor MMAA scores
      between the two groups. In addition, based on Spearman's rho correlational
      analysis, there were significant associations of QLS scores with ISS scores (r = 
      0.236) and with MMAA "total errors" scores (r = 0.174). Logistic regression
      demonstrated that only QLS scores predicted suicidality. CONCLUSION: Thirty-six
      percent of our sample had at least mild degrees of suicidality. Lower quality of
      life appears to be an important predictor of suicidality.

PMID- 17506026
TI  - Intradiol pathway of para-cresol conversion by Rhodococcus opacus 1CP.
AB  - The growth of Rhodococcus opacus 1CP in medium with different concentrations of p
      cresol as the sole source of carbon and energy was studied. It was shown that the
      optimal concentration of p-cresol was 600 mg/L. The ability of this strain to
      transform practically all amounts of p-cresol to 4-methylcatechol followed by its
      utilization through ortho-pathway was shown. New enzymes (4-methylcatechol 1,2
      dioxygenase, catechol 1,2-dioxygenase, and methylmuconate cycloisomerase) were
      purified to homogeneity and characterized. Based on the data obtained on p-cresol
      degradation, formation of intermediates, and the enzymes participating in this
      pathway, we suggest an ortho-pathway of p-cresol degradation by R. opacus 1CP
      through 4-methylcatechol and 3-methyl-cis, cis-muconate.

PMID- 17506027
TI  - Cooperation of plants and microorganisms: getting closer to the genetic
      construction of sustainable agro-systems.
AB  - The molecular research into two types of beneficial plant-microbe symbioses is
      reviewed: nutritional (with N(2)-fixing bacteria or mycorrhizal fungi) and
      defensive (with endo- and epiphytic microbes suppressing pathogens and
      phytophagans). These symbioses are based on the signaling interactions that
      result in the development of novel tissue/cellular structures and of extended
      metabolic capacities in the partners, which greatly improve the adaptive
      potential of plants due to a decrease in their sensitivity to biotic and abiotic
      stresses. The molecular, genetic and ecological knowledge on plant-microbe
      interactions provides a strategy for the organization of sustainable crop
      production based on substituting the agrochemicals (mineral fertilizers,
      pesticides) by microbial inoculants. An improvement of plant-microbe symbioses
      should involve the coordinated modifications in the partners' genotypes resulting
      in highly complementary combinations. These modifications should be based on the
      broad utilization of genetic resources from natural symbiotic systems aimed at:
      (i) increased competitiveness of the introduced (effective) with respect to local
      (ineffective) microbial strains, and (ii) overcoming the limiting steps in the
      metabolic machineries of the symbiotic systems.

PMID- 17506028
TI  - Streamlined variance calculations for semiparametric mixed models.
AB  - Semiparametric mixed model analysis benefits from variability estimates such as
      standard errors of effect estimates and variability bars to accompany curve
      estimates. We show how the underlying variance calculations can be done extremely
      efficiently compared with the direct naive approach. These streamlined
      calculations are linear in the number of subjects, representing a two orders of
      magnitude improvement.

PMID- 17506029
TI  - Elevated levels of endogenous apoptotic DNA and IFN-alpha in complement C4
      deficient mice: implications for induction of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE), an autoimmune disease characterized by
      chronic nephritis, arthritis and dermatitis, and the presence of antinuclear
      autoantibodies, is associated with complement factor deficiencies in the
      classical activation pathway. In addition, IFN-alpha seems to be a key cytokine
      in SLE as an activated IFN-alpha system is regularly observed in patients with
      SLE. Here, we demonstrate that in lupus-susceptible, complement C4-deficient mice
      the lack of complement results in elevated intravascular levels of apoptotic DNA.
      The apoptotic DNA is targeted to the splenic marginal zone where it accumulates
      and induces IFN-alpha. As such, we present here a unifying hypothesis for the
      induction of SLE that incorporates the role of complement deficiency and elevated
      levels of IFN-alpha.

PMID- 17506030
TI  - Spontaneous or Mycobacterium tuberculosis-induced apoptotic neutrophils exert
      opposite effects on the dendritic cell-mediated immune response.
AB  - Polymorphonuclear neutrophils (PMN) modulate the adaptive immune response through
      interactions with immature dendritic cells (iDC) while spontaneous apoptotic
      neutrophils PMNapo (PMNapo) may have an inhibitory effect on DC functions. We
      investigate the effect exerted by PMNapo in DC maturation and the role of
      Mycobacterium tuberculosis (Mtb)-induced PMNapo in the cross-presentation of
      mycobacterial antigens. We demonstrate that Mtb triggers the maturation of iDC
      while it is impaired by the presence of PMNapo, which abrogate Mtb-induced
      expression of costimulatory and HLA class II molecules, reducing IL-12 and IFN
      gamma release by DC and partially inhibiting Mtb-driven lymphocyte proliferation.
      This inhibitory effect is not observed in already Mtb-matured DC, and it involves
      a direct interaction between DC and PMNapo, as supernatants from PMNapo cultures
      do not reveal this effect. Although PMNapo do not alter Mtb/DC-SIGN interaction,
      they affect the intracellular signals leading to DC maturation without requiring
      their entry into DC. Phagocytosis of Mtb-induced PMNapo by iDC leads to
      lymphoproliferation, which is significantly reduced by blocking CD36 and not DC
      SIGN on iDC. Therefore, cross-presentation of Mtb antigens is taking place. Our
      findings suggest that the inflammatory milieu is subjected to a fine balance
      between non-infected and Mtb-induced PMNapo: non-infected PMNapo limiting
      inflammation and Mtb-induced PMNapo generating a specific immune activity.

PMID- 17506031
TI  - CD8alpha/alpha homodimers fail to function as co-receptor for a CD8-dependent
      TCR.
AB  - In this study, we have started to dissect the molecular basis of CD8 dependence
      of a high and low avidity CTL clone specific for the same peptide epitope. Using
      anti-CD8alpha and anti-CD8beta antibodies, we found that cytotoxicity and IFN
      gamma production by high but not by low avidity CTL was strongly CD8 dependent.
      We isolated the TCR genes of both types of CTL clones and used retroviral gene
      transfer to analyse the function of these TCR in primary T cells of wild-type and
      CD8beta-deficient mice. Both TCR triggered antigen-specific killing in wild-type
      T cells, and blocking experiments showed that CD8 dependence/independence co
      transferred with the TCR into primary T cells, indicating that it was dictated by
      the TCR itself. Gene transfer experiments into CD8beta-deficient T cells revealed
      that only the TCR derived from the CD8-independent CTL clone elicited antigen
      specific cytotoxicity, while the CD8-dependent TCR was non-functional in the
      absence of the CD8beta-chain. These data indicate a striking difference between
      CD8alpha/beta heterodimers and CD8alpha/alpha homodimers as only the former were
      able to provide co-receptor function for the CD8-dependent TCR.

PMID- 17506032
TI  - Human keratinocyte induction of rapid effector function in antigen-specific
      memory CD4+ and CD8+ T cells.
AB  - The ability of human keratinocytes to present antigen to T cells is controversial
      and, indeed, it has been suggested that keratinocytes may promote T cell
      hyporesponsiveness. Furthermore, it is unclear whether keratinocytes can process
      antigen prior to MHC class I and class II presentation. We tested the ability of
      keratinocytes to induce functional responses in epitope-specific CD4+ and CD8+
      memory T cells using peptides, protein and recombinant expression vectors as
      sources of antigen. Keratinocytes were able to efficiently process and present
      protein antigen to CD4+ T cells, resulting in cytokine secretion (Th1 and Th2).
      This interaction was dependent on keratinocyte expression of HLA class II and
      ICAM-1, which could be induced by IFN-gamma. In addition, keratinocytes could
      present virally encoded or exogenous peptide to CD8+ T cells, resulting in T cell
      cytokine production and target cell lysis. Finally, T cell lines grown using
      keratinocytes as stimulators showed no loss of function. These findings
      demonstrate that keratinocytes are able to efficiently process and present
      antigen to CD4+ and CD8+ memory T cells and induce functional responses. The
      findings have broad implications for the pathogenesis of cutaneous disease and
      for transcutaneous drug or vaccine delivery.

PMID- 17506033
TI  - Activities of erythropoietin on tumors: an immunological perspective.
AB  - There is a growing interest in the non-erythropoietic, tissue-protective and
      restorative actions of erythropoietin (EPO). While studies in this field have
      indicated that EPO can ameliorate chemotherapy-induced peripheral neuropathy and
      cardiotoxicity, the issue whether EPO can positively or negatively affect cancer
      patients is a hot one. In this debate, many activities of EPO are being
      considered, including tissue/neuroprotection, angiogenesis, anti-inflammatory
      activity, growth promotion, and inhibition of apoptosis. However, few studies
      have explored the interactions of EPO with the immune system. A study in this
      issue of the European Journal of Immunology by Katz et al. adds one new piece to
      the puzzle by showing that EPO can stimulate B cell-mediated immunity.

PMID- 17506034
TI  - Recirculating CD4 memory T cells mount rapid secondary responses without major
      contributions from follicular CD4 effectors and B cells.
AB  - For weeks after primary immunization with thymus-dependent antigens the
      responding lymph nodes contain effector CD4 T cells in T zones and germinal
      centers as well as recirculating memory T cells. Conversely, remote nodes, not
      exposed to antigen, only receive recirculating memory cells. We assessed whether
      lymph nodes with follicular effector CD4 T cells in addition to recirculating
      memory CD4 T cells mount a more rapid secondary response than nodes that only
      contain recirculating memory cells. Also, the extent to which T cell frequency
      governs accelerated CD4 T cell recall responses was tested. For this, secondary
      antibody responses to a superantigen, where the frequency of responding T cells
      is not increased at the time of challenge, were compared with those to
      conventional protein antigens. With both types of antigens similar accelerated
      responses were elicited in the node draining the site of primary immunization and
      in the contralateral node, not previously exposed to antigen. Thus recirculating
      memory cells are fully capable of mounting accelerated secondary responses,
      without the assistance of CD4 effector T cells, and accelerated memory responses
      are not solely dependent on higher T cell frequencies. Accelerated memory CD4 T
      cell responses were also seen in B cell-deficient mice.

PMID- 17506035
TI  - Lung CD11c+ cells from mice deficient in Epstein-Barr virus-induced gene 3 (EBI
      3) prevent airway hyper-responsiveness in experimental asthma.
AB  - Epstein-Barr virus-induced gene (EBI)-3 codes for a soluble type 1 cytokine
      receptor homologous to the p40 subunit of IL-12 that is expressed by antigen
      presenting cells following activation. Here, we analyzed the functional role of
      EBI-3 in a murine model of asthma associated with airway hyper-responsiveness
      (AHR) in ovalbumin-sensitized mice. Upon allergen challenge, EBI-3-/- mice showed
      less severe AHR, decreased numbers and degranulation of eosinophils and a
      significantly reduced number of VCAM-1+ cells in the lungs as compared to wild
      type littermates. We thus analyzed lung CD11c+ cells before and after allergen
      challenge in these mice and found that before allergen challenge, lung CD11c+
      cells isolated from EBI-3-/- mice express markers of a more plasmacytoid
      phenotype without releasing IFN-alpha as compared to those from wild-type
      littermates. Moreover, allergen challenge induced the development of myeloid
      CD11c+ cells in the lungs of EBI-3-/- mice, which released increased amounts of
      IL-10 and IL-12 while not expressing IFN-alpha. Finally, inhibition of EBI-3
      expression in lung DC could prevent AHR in adoptive transfer studies by
      suppressing mediator release of effector cells into the airways. These results
      indicate a novel role for EBI-3 in controlling local immune responses in the
      lungs in experimental asthma.

PMID- 17506036
TI  - Automatic assessment of dynamic contrast-enhanced MRI in an ischemic rat hindlimb
      model: an exploratory study of transplanted multipotent progenitor cells.
AB  - This study presents computerized automatic image analysis for quantitatively
      evaluating dynamic contrast-enhanced MRI in an ischemic rat hindlimb model. MRI
      at 7 T was performed on animals in a blinded placebo-controlled experiment
      comparing multipotent adult progenitor cell-derived progenitor cell (MDPC)
      treated, phosphate buffered saline (PBS)-injected, and sham-operated rats.
      Ischemic and non-ischemic limb regions of interest were automatically segmented
      from time-series images for detecting changes in perfusion and late enhancement.
      In correlation analysis of the time-signal intensity histograms, the MDPC-treated
      limbs correlated well with their corresponding non-ischemic limbs. However, the
      correlation coefficient of the PBS control group was significantly lower than
      that of the MDPC-treated and sham-operated groups. In semi-quantitative
      parametric maps of contrast enhancement, there was no significant difference in
      hypo-enhanced area between the MDPC and PBS groups at early perfusion-dependent
      time frames. However, the late-enhancement area was significantly larger in the
      PBS than the MDPC group. The results of this exploratory study show that MDPC
      treated rats could be objectively distinguished from PBS controls. The
      differences were primarily determined by late contrast enhancement of PBS-treated
      limbs. These computerized methods appear promising for assessing perfusion and
      late enhancement in dynamic contrast-enhanced MRI.

PMID- 17506037
TI  - Reference ranges for fetal ventricular width: a non-normal approach.
AB  - OBJECTIVES: Normal ranges for fetal cerebral ventricular width are usually based
      on parametric methods, which define cut-off values based on means and standard
      deviations. We aimed to construct reference charts based on a large sample and
      using a method that better fits with skewed measurements. METHODS: In November
      2001-December 2005, a single operator, who was unaware of the subsequent
      analysis, performed prospectively and routinely fetal cerebral ventricular width
      measurements. We used the LMS method (which summarizes the changing distribution
      of a variable of interest according to a covariate (gestational age) using three
      curves representing the median (M), the coefficient of variation (S) and skewness
      (L)) to describe the distribution of measurements with gestational age. The LMS
      method provides a general method for fitting smooth centile curves to reference
      data. It utilizes the power transformation family of Box and Cox to allow the
      skewness of the measurement distribution, as well as the median and variability,
      to vary with age. The theoretical proportion of fetal ventricular widths > or =
      10 mm based on the LMS method and on methods based on the assumption of normality
      were compared with the actual proportion using binomial tests. The influence on
      ventricular size of gestational age and fetal gender and presentation was
      assessed using robust regression methods. RESULTS: Included in the study were
      4769 ventricular measurements, 42 (0.88%) of which were > or = 10 mm. The LMS
      method allowed us to fit the skewness of the measurements and identified slight
      changes throughout gestation. The actual proportion of measurements > or = 10 mm
      was not different from that expected according to the LMS method (0.88% vs. 1%, P
      = 0.25), whereas it was significantly different from that based on the classical
      normal approximation (0.88% vs. 0.4%, P < 0.0001). There was a significant
      difference with gender (males: + 0.29 +/- 0.042 mm as compared to females, P <
      0.0001), but there was no difference with fetal presentation (P = 0.4).
      CONCLUSION: We present new reference values for fetal ventricular width based on
      the LMS method. A fixed cut-off value of 10 mm identifies around 1% of the
      population throughout gestation, which is more than that calculated in previous
      studies.

PMID- 17506038
TI  - Single-molecule technology for rapid detection of DNA hybridization based on
      resonance light scattering of gold nanoparticles.

PMID- 17506039
TI  - Does negative hyperconjugation assist enzymatic dehydrogenations?

PMID- 17506040
TI  - Luminescent coordination compound nanospheres for water determination.

PMID- 17506041
TI  - Semiconducting cyanide-transition-metal nanotubes.
AB  - We propose a new type of structurally simple and energetically stable cyanide
      transition-metal nanotube, based on the planar structure of M(CN)2, (M = Ni, Pd,
      Pt). These nanotubes have a semiconducting character with a large bandgap (2-3
      eV) that is insensitive to chirality and diameter. The energetic, electronic, and
      mechanical properties of these materials in both planar and tubular forms are
      studied through first-principles density functional theory calculations. The
      calculations reveal interesting multicenter bonding features, which should lead
      to preferential growth of tubes of a particular chirality. These intrinsically
      semiconducting nanotubes can be readily p- or n-doped, which makes them good
      candidates for nanoscale elements in electronic devices.

PMID- 17506042
TI  - Apparent asymmetry in fingerprint similarity searching is a direct consequence of
      differences in bit densities and molecular size.
AB  - Recently, systematic similarity calculations using Tversky coefficients have
      suggested that putting higher weight on bit settings of active reference
      molecules (templates) than database compounds increases hit rates in similarity
      searching using 2D fingerprints. These findings have been interpreted as evidence
      for "asymmetry" in chemical similarity searching. We have thoroughly analyzed
      this phenomenon and demonstrate that apparent asymmetry in similarity search
      calculations is a direct consequence of differences in fingerprint bit densities,
      which often correlate with differences in molecular size. Accordingly, a size
      independent fingerprint with constant bit density does not produce asymmetrical
      search results. For Tversky similarity calculations, differences in fingerprint
      bit densities between active and inactive compounds determine which weighting
      factors produce high hit rates.

PMID- 17506043
TI  - The construction of a functional photoactivatable cancer targeting bispecific
      antibody conjugate.

PMID- 17506044
TI  - Thuggacins, macrolide antibiotics active against Mycobacterium tuberculosis:
      isolation from myxobacteria, structure elucidation, conformation analysis and
      biosynthesis.
AB  - Two novel antibiotics, thuggacin A (1) and B (2), were isolated from the
      myxobacterium Sorangium cellulosum. 1 and 2 are unique thiazole-containing
      macrolides with side chains on both sides of the lactone group. Upon standing in
      solution, thuggacin A (1) rearranges by acyl migration of the lactone group to
      give a mixture with thuggacins B (2) and C (3). NOEs and vicinal coupling
      constants within the lactone ring provided distinct data for the generation of a
      structure model by PM3 calculations, which allowed an analysis of the
      conformation in solution and the relative configuration of six asymmetric
      centres. A minor sorangium metabolite was identified as 13-methyl-thuggacin A
      (4). Furthermore, two natural thuggacin variants, 5 and 6, were found in another
      myxobacterium, Chondromyces crocatus. In these variants, one side chain is
      replaced by a methyl group and a hydroxy group is repositioned to give a primary
      alcohol at the former methyl site, in an alpha position with respect to the
      thiazole ring. 1 proved to be active against clinical isolates and reference
      strains of Mycobacterium tuberculosis. Preliminary studies on the mechanism of
      action indicate inhibition of the cellular electron-transport chain.

PMID- 17506045
TI  - Influence of copper salts, solvents, and ligands on the structures of
      precatalytic phosphoramidite copper complexes for conjugate addition reactions.
AB  - For copper-catalyzed enantioselective conjugate addition reactions of organozinc
      reagents, the available knowledge about the mechanism and the structures involved
      is still insufficient to understand in detail the strong influences of solvent,
      salt, and ligand size, or to enable a rational control of this reaction.
      Screening with three phosphoramidite ligands and four copper(I) salts using NMR
      spectroscopy has revealed a binuclear copper complex with mixed
      trigonal/tetrahedral stereochemistry as the basic structural motif of the ground
      state of precatalysts with highly stereoselective ligands. Ligands with smaller
      amine moieties allow higher coordination numbers and higher aggregation levels,
      leading to reduced ee values. Since the ESI mass spectra of several precatalytic
      copper halide complexes show a striking correlation with the structures observed
      in solution, ESI-MS may be used as a fast tool to determine the maximum number of
      phosphoramidite ligands attached to copper.

PMID- 17506046
TI  - A conceptual DFT approach for the evaluation and interpretation of redox
      potentials.
AB  - Conceptual DFT aims at describing the properties of molecules in interactions by
      using chemical reactivity descriptors. Herein, the redox behaviour of a given
      species, as quantified by the redox potential, is linked to DFT-based
      descriptors. We made use of a hierarchical decomposition of the corresponding
      half-reactions into one-electron reduction, protonation, dissociation and water
      forming or dissociation reactions. Most of these reactions can be readily
      described through reactivity descriptors, such as the electrophilicity,
      nucleofugality and electrofugality, as defined in conceptual DFT. The final
      expression linking the corresponding free energy changes to the redox potential
      seems to give correct predictions for the redox potentials of bromo, chloro and
      nitro oxo acids in the gas phase, as in a polarised continuum model.

PMID- 17506047
TI  - Ring-borylated 15-electron and 17-electron ansa-chromocene complexes, their
      physical properties and molecular structures.
AB  - A detailed study of the thermal decomposition of the zwitterionic, ring-borylated
      ansa-chromocene hydrido carbonyl complex
      [Cr(CO)H{Me(4)C(2)(C(5)H(4))[C(5)H(3)B(C(6)F(5))(3)]}] (2) is described. This
      complex is formed in the reaction between [Cr(CO){Me(4)C(2)(C(5)H(4))(2)}] (1)
      and B(C(6)F(5))(3) in toluene at -78 degrees C. Above -25 degrees C, 2 decomposes
      to a 50:50 mixture of the low-spin, 17e Cr(III) complexes
      [Cr(CO){Me(4)C(2)(C(5)H(4))[C(5)H(3)B(C(6)F(5))(3)]}] (3b) and
      [Cr(CO){Me(4)C(2)(C(5)H(4))(2)}][HB(C(6)F(5))(3)] (4). Carbon monoxide
      elimination from 3 b generates high-spin, 15 e
      [Cr{Me(4)C(2)(C(5)H(4))[C(5)H(3)B(C(6)F(5))(3)]}] (3a), which coordinates two
      other electron-donating ligands, such as xylyl isocyanide, PMe3, and PPh(2)Me to
      form the low-spin, 17 e electron complexes 3c, 3d, and 3e, respectively. High
      spin, 15 e [Cr{Me(4)C(2)(C(5)H(4))(2)}][HB(C(6)F(5))(3)] (5) is generated by
      heating 3 b in toluene at 100 degrees C and periodically removing the evolved CO.
      Efforts to isolate more than a few X-ray quality crystals of 5 were thwarted by
      its tendency to form an insoluble precipitate (6) with the same molecular
      formula. Heating the solution of 5 at 120 degrees C results in its partial
      conversion (ca. 28 %) to 3a, thereby allowing the formation of 3a in yields as
      high as 74 % from the reaction between 1 and B(C(6)F(5))(3). The X-ray crystal
      structures of 3 b-e and 5 are described. Cyclic voltammetry measurements on 3 a-e
      reveal a dramatic reduction in the redox potentials of the complexes relative to
      their non-borylated analogues. DFT calculations show that this is due primarily
      to electrostatic stabilization of the oxidized species by the negatively charged
      borylate group. EPR and 19F NMR spectroscopy allow 3a to be distinguished from
      its Lewis base adducts 3 b-e and reveal the relative affinities of different
      Lewis bases for the chromium.

PMID- 17506048
TI  - Bridge over troubled water: resolving the competing photosystem II crystal
      structures.
AB  - Density functional theory (DFT) calculations, at the Becke-Perdew/TZP level of
      theory, were used to investigate a set of CaMn(4)-containing clusters that model
      the active site of the water-oxidizing complex (WOC) of photosystem II (PSII).
      Metal-atom positions for three representative isomeric clusters of the formula
      [CaMn(4)C(9)N(2)O(16)H(10)](+)4 H(2)O are in good agreement with the disparate
      Mn(4) geometries of the three most recent X-ray crystal structures. Remarkably,
      interconversion between these three isomeric clusters is found to be facile,
      resulting from subtle changes in the coordination environment around the CaMn(4)
      centre. This result provides a clear rationalisation of the marked differences in
      reported crystal structures. Recent concerns have been raised regarding the
      opportunity for X-ray-damage-induced distortion of the metal-containing active
      centre during crystallographic analysis. Our calculations suggest that an even
      greater problem may be presented by the apparent fluxionality of the CaMn(4)
      skeleton within the active centre. Structural rearrangement may well precede
      crystallographic analysis, for example by the preferential "freezing-out" of one
      of several near-isoenergetic structures during the workup for crystallisation.
      This prospect, which our calculations cannot exclude, highlights the difficulties
      that will continue to be faced by experimentalists seeking unambiguous structural
      information on the WOC's active site.

PMID- 17506049
TI  - Dititanium-containing 19-tungstodiarsenate(III) [Ti2(OH)2As2W19O67(H2O)]8-:
      synthesis, structure, electrochemistry, and oxidation catalysis.
AB  - The dititanium-containing 19-tungstodiarsenate(III)
      [Ti(2)(OH)(2)As(2)W(19)O(67)(H(2)O)](8-) (1) has been synthesized and
      characterized by IR, TGA, elemental analysis, electrochemistry, and catalytic
      studies. Single-crystal X-ray analysis was carried out on
      Cs(8)[Ti(2)(OH)(2)As(2)W(19)O(67)(H(2)O)].2CsCl.12H(2)O (Cs-1), which
      crystallizes in the monoclinic system, space group P2(1)/m, with a=12.7764(19),
      b=19.425(3), c=18.149(3) A, beta=110.234(3) degrees, and Z=2. Polyanion 1
      comprises two (B-alpha-As(III)W(9)O(33)) Keggin moieties linked through an
      octahedral {WO(5)(H(2)O)} fragment and two unprecedented square-pyramidal
      {TiO(4)(OH)} groups, leading to a sandwich-type structure with nominal C(2v)
      symmetry. Synthesis of 1 was accomplished by reaction of TiOSO(4) and
      K(14)[As(2)W(19)O(67)(H(2)O)] in a 2:1 molar ratio in aqueous, acidic medium (pH
      2). Polyanion 1 could also be isolated as a tetra-n-butyl ammonium (TBA) salt,
      {(n-C(4)H(9))(4)N}(5)H(3)[Ti(2)(OH)(2)As(2)W(19)O(67)(H(2)O)] (TBA-1). TBA-1 was
      studied by cyclic voltammetry in acetonitrile (MeCN) solutions containing 0.1 M
      LiClO(4) and compared with the results obtained with Cs-1 in aqueous media. In
      MeCN, the Ti(IV) and W(VI) waves could not be separated distinctly. An important
      adsorption phenomenon on the glassy carbon working electrode was encountered both
      in cyclic voltammetry and in controlled potential electrolysis and was confirmed
      by Electrochemical Quartz Crystal Microbalance (EQCM) studies on a carbon film.
      TBA-1, dissolved in MeCN, reacts with H(2)O(2) to give peroxo complexes stable
      enough for characterization by UV-visible spectroscopy, cyclic voltammetry, and
      EQCM. TBA-1 shows high catalytic activity (TOF=11.3 h(-1)) in cyclohexene
      oxidation with aqueous H(2)O(2) producing products typical of a heterolytic
      oxidation mechanism. The stability of TBA-1 under turnover conditions was
      confirmed by using IR, UV-visible spectroscopy as well as cyclic voltammetry.

PMID- 17506050
TI  - Adaptive recognition of small molecules by nucleic acid aptamers through a label
      free approach.
AB  - We report a novel label-free method for the investigation of the adaptive
      recognition of small molecules by nucleic acid aptamers using capillary
      electrophoresis analysis. Cocaine and argininamide were chosen as model
      molecules, and the two corresponding DNA aptamers were used. These single-strand
      DNAs folded into their specific secondary structures, which were mainly
      responsible for the binding of the target molecules with high affinity and
      specificity. For molecular recognition, the nucleic acid structures then
      underwent additional conformational changes, while keeping the target molecules
      stabilized by intermolecular hydrogen bonds. The intrinsic chemical and physical
      properties of the target molecules enabled them to act as indicators for adaptive
      binding. Thus any labeling or modification of the aptamers or target molecules
      were made obsolete. This label-free method for aptamer-based molecular
      recognition was also successfully applied to biological fluids and therefore
      indicates that this approach is a promising tool for bioanalysis.

PMID- 17506051
TI  - A highly efficient asymmetric organocatalytic aldol reaction in a ball mill.
AB  - Anti-aldol products with up to >99 % enantiomeric excess (ee) have been obtained
      by proline catalysis in excellent yields under experimentally simple solvent-free
      conditions. Efficient mixing of all the components is accomplished by applying a
      mechanochemical technique (ball milling). The catalysis is air and moisture
      tolerant and can be performed with non-purified starting materials. Even mixtures
      of solely solid compounds react, giving (mostly solid) products through a
      partially homogeneous (honey-like) intermediate melt. Since the reactant ratio is
      almost 1:1 (avoiding the common excess of ketone), the product isolation is easy
      leading to high aldol product yields.

PMID- 17506052
TI  - Reaction rates as a function of scale within ionic liquids: microscale in droplet
      microreactors versus macroscale reactions in the case of the Grieco three
      component condensation reaction.
AB  - Task-specific ionic liquids (TSILs) and more specifically binary task-specific
      ionic liquids (BTSILs), a unique subclass, have been shown to be excellent
      supports for solution-phase chemistry. The negligible volatility of ionic liquids
      enables their use as stable droplet microreactors in atmospheric environments
      without oil protection or confinement. These droplets can be moved, merged and
      mixed by electrowetting on a chip. Solution-phase synthesis can be performed on
      these open digital microfluidic labs-on-a-chip as illustrated by a study of the
      Grieco three-component reaction in [tmba][NTf(2)]-droplet (tmba=N-trimethyl-N
      butylammonium NTf(2)=bis(trifluoromethylsulfonyl)imide) microreactors. A detailed
      study of matrices and scale effects on conversion and kinetic rates of this three
      component condensation is presented in this paper. Reactions have been shown to
      be slower in droplets than in batches in the absence of additional mixing. Also,
      a significant influence of the ionic-liquid matrix has been observed. Finally, an
      increase of droplet's temperature resulted in a kinetics enhancement so as to
      reach macroscale reaction rates, probably because of a much better mixing of
      reaction's components involving a Marangoni's effect.

PMID- 17506053
TI  - Fibrous aggregation of magnetite nanoparticles induced by a time-varied magnetic
      field.

PMID- 17506054
TI  - Hydrogen peroxide triggered prochelator activation, subsequent metal chelation,
      and attenuation of the fenton reaction.

PMID- 17506055
TI  - Chivosazole A--elucidation of the absolute and relative configuration.

PMID- 17506056
TI  - A distinctive organocatalytic approach to complex macromolecular architectures.

PMID- 17506057
TI  - Chemoenzymatic enrichment of phosphotyrosine-containing peptides.

PMID- 17506058
TI  - Description of a cranial endocast from the fossil mammal Vincelestes neuquenianus
      (Theriiformes) and its relevance to the evolution of endocranial characters in
      therians.
AB  - We generated a digital cranial endocast (infilling of the braincase) of
      Vincelestes neuquenianus, a Cretaceous theriiform mammal from Argentina, to
      achieve two goals. First, we described this endocast of Vincelestes to
      reconstruct the brain, associated soft-tissue structures, and internal
      osteological features. This report represents the first description of an
      endocast from a stem therian that is near crown group Theria (marsupials,
      placentals, and all descendants of that ancestor). Second, we examined 21
      morphological characters related to the morphology of endocasts and endocranial
      osteology across 19 taxa (including Vincelestes) in the context of a current
      hypothesis about mammal phylogeny to identify potential synapomorphies for
      Theria. The digital endocast of Vincelestes is mostly complete, facilitating
      description in all views and allowing collection of accurate linear and
      volumetric measurements. However, it is unclear if the midbrain is exposed on the
      dorsal surface of the brain because of damage to this region of the endocast.
      Other portions of this specimen are extraordinarily well preserved, allowing
      identification of the accessory olfactory bulbs on the endocast, an ossified falx
      cerebri, and an osseous tentorium. The encephalization quotient (EQ) calculated
      for Vincelestes falls within the range of EQs of crown therians. Comparison of
      the endocranial characters across different mammalian taxa did not reveal any new
      synapomorphies for the clade Theria.

PMID- 17506059
TI  - Receptor activator of nuclear factor kappa B ligand (RANKL) modulates the
      expression of genes involved in apoptosis and cell cycle in human osteoclasts.
AB  - It has been clearly established that receptor activator of nuclear factor kappa B
      ligand (RANKL) is a key cytokine involved in the differentiation of osteoclastic
      precursors of the monocytic/macrophagic lineage. However, relatively little
      information is available on the ability of RANKL to modulate the expression of
      genes controlling cell survival/apoptosis and proliferation in human osteoclastic
      cells in comparison to macrophages. For this purpose, CD14+ human peripheral
      blood mononuclear cells, which express the cognate high affinity receptor
      activator of nuclear factor kappa B (RANK), were differentiated along the
      macrophagic or osteoclastic lineage by adding macrophage-colony stimulating
      factor (M-CSF) or M-CSF plus RANKL in culture for 12 days. RANKL up-regulated the
      expression of the chemokine MIP1alpha, which potentiates osteoclastic
      differentiation and simultaneously activated both anti-apoptotic (Bcl-2) and pro
      apoptotic (CIDEB, PYCARD, and BAK-1) genes. Moreover, RANKL markedly up-regulated
      cylin D2, while it significantly decreased the levels of cyclin A, cyclin
      dependent kinase 2, and other cyclin-dependent kinases, in keeping with the
      notion that end-stage osteoclasts are nondividing cells. Finally, a long-term
      exposure of RANKL up-regulated the adaptor protein TRAF3 but not TRAF6.

PMID- 17506060
TI  - Measurement of the vertebral canal dimensions of the neck of the rat with a
      comparison to the human.
AB  - The aim of this study was to determine the dimensions of the vertebral canal in
      the neck of the rat, because little is known about the morphology of the rat's
      cervical spine. A comparison then was made to the vertebral canal in the neck of
      the human. In part 1 of this study, we determined the precision of three
      different methods to measure the vertebral canal. The error (coefficient of
      variation) in these methods was found to range from 1 to 8%. In part 2, we used a
      computer-based system to measure digital images of the vertebra and determined
      the anterior to posterior and the transverse vertebral canal dimensions in the
      neck of 19 young adult Sprague-Dawley rats. The anterior to posterior dimension
      of the vertebral canal was greatest at the upper cervical (C1-C2) level and
      progressively decreased in the more caudal segments (C3-T1). The transverse
      dimension was greatest at the atlas (C1) vertebra and smallest at the axis (C2)
      vertebra with a steady increase in the transverse dimension with more caudal
      segments and a maximum transverse dimension at the level of the C6 and C7
      vertebra. This study has demonstrated that the vertebral canal in the neck of
      young adult rats is similar in some regards to that of human. However, there are
      clear differences between the rat and human. These may be associated with
      differences in the morphology of the spinal cord or postural differences such as
      the cervicothoracic lordosis in bipeds compared with that in quadrupeds.

PMID- 17506064
TI  - Hydroxyurea therapy for management of secondary erythrocytosis in cyanotic
      congenital heart disease.
AB  - Secondary erythrocytosis in cyanotic congenital heart disease (CCHD) causes
      substantial morbidity because of complications of hyperviscosity, including
      stroke and chronic end organ damage. Phlebotomy provides temporary improvement
      but leads to iron deficiency and can actually increase blood viscosity. We
      describe the successful use of hydroxyurea (hydroxycarbamide) in four patients
      with uncorrected CCHD and symptomatic secondary erythrocytosis. In all patients,
      hydroxyurea improved symptoms of hyperviscosity. Substantial decreases in the red
      blood cell (RBC) count were observed, along with increases in the mean
      corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), leading to only
      modest declines in the circulating hemoglobin concentration. Two patients
      experienced transient mild myelosuppression, which promptly resolved with dose
      reduction of hydroxyurea. Hydroyxurea provides a novel and useful therapeutic
      approach to reduce hyperviscosity from secondary erythrocytosis in patients with
      CCHD, while preserving oxygen carrying capacity and avoiding iron depletion by
      phlebotomy.

PMID- 17506065
TI  - Benzene-induced acute myeloid leukemia: a clinician's perspective.
AB  - Benzene-induced acute myeloid leukemia (AML) is considered a secondary form of
      AML, based both in theory and on limited cohort observations. Its latency,
      cytogenetic aberrations, and clinical features are thought similar to, or
      identical with, AML resulting from the use of modern day cytotoxic agents for
      chemotherapy and immunotherapy. Although distinction between secondary AML and
      the far more common de novo AML is difficult to establish with certainty in any
      given case, latency from toxic therapeutic and environmental exposure and certain
      clinical and pathological features generally separate these two entities. AML is
      the only human neoplasm proven to be potentially caused by benzene, which
      actually is an obsolete form of chemotherapy. Despite many years of environmental
      regulation, alleged toxic exposure to this ubiquitous chemical has become an
      expanding area of litigation. A review of benzene-induced AML suggests that, in
      developed countries, this entity should no longer merit serious consideration
      among workers in the modern petrochemical industry and related fields.

PMID- 17506066
TI  - Normal hematopoietic function and multiple bone marrow clonal abnormalities in a
      patient with acute myeloid leukemia after two mismatched stem-cell transplants
      with graft failure and autologous reconstitution.
AB  - A 13-year-old male with primary refractory acute myelogenous leukemia (AML-M0),
      underwent two mismatched stem cell transplantations (SCT) and experienced graft
      failure after both procedures. Of interest, his peripheral blood cell counts are
      normal 7 years after his first SCT, his bone marrow is morphologically normal,
      however, cytogenetic analysis reveals multiple recurring cytogenetic
      abnormalities. This is the third case of chromosomal instability with
      morphological normal marrow and peripheral blood to be reported, these rare cases
      suggest that hematopoietic stem cells must have compensating mechanisms that
      allow normal function despite extensive chromosomal damage, supporting the notion
      that normal marrow function is possible even with extensive chromosomal damage.

PMID- 17506067
TI  - The role of autoantibody-producing plasma cells in immune thrombocytopenic
      purpura refractory to rituximab.
AB  - Rituximab is becoming popular as a treatment for immune thrombocytopenic purpura
      (ITP). We report here a patient with ITP, who initially responded to rituximab,
      but later became refractory. In this patient, the appearance of plasma cells
      producing anti-platelet autoantibodies is likely to be one of the mechanisms for
      rituximab resistance.

PMID- 17506068
TI  - Flow cytometric evaluation of circulating endothelial cells: a new protocol for
      identifying endothelial cells at several stages of differentiation.
AB  - Several factors may influence the analysis of endothelial cells (ECs) by flow
      cytometry: separation of mononuclear cell, washing and centrifugation steps,
      panel of monoclonal antibodies, and the lack of standardization of gating
      technique. Therefore, the reliable quantification of ECs remains a technical
      challenge. The purpose of this study is to define a new flow cytometric protocol
      to characterize and quantitate ECs. In previous investigations, increased numbers
      of circulating ECs have been found in sickle cell disease. The patients with
      sickle cell disease might provide useful material for the study. We performed
      flow cytometry on whole blood from 20 normal controls and 31 patients with sickle
      cell disease (20 patients with steady-state disease and 11 patients with vaso
      occlusive crises) using a lyse/no-wash procedure, specific and nonspecific
      antibody combinations (CD146, CD144, CD34, and CD117), and broad gating. This
      protocol produced much higher values for the number of circulating ECs (a mean of
      2,396.55 +/- 658.37 ECs/mL in controls vs 6,709.60 +/- 1,772.32 ECs/mL in the
      steady-state group, or 18,213.50 +/- 8,451 in the vaso-occlusive crises group, P
      < 0.001 for both), and also showed variable EC size and granularity, which may
      reflect activated, or early release ECs. This novel protocol performed comparably
      in terms of reproducibility, reliability, and dilution linearity with a
      previously described protocol. This approach has significant advantages for the
      characterization and quantitation ECs compatible with the pathophysiology. Using
      the specific antibodies, CD146 and CD144, together may give more informative EC
      data than the general approach used.

PMID- 17506070
TI  - Treatment of acquired severe aplastic anemia with antilymphocyte globulin,
      cyclosporin A, methyprednisolone, and granulocyte colony-stimulating factor.
AB  - Fifty-six adult patients with newly diagnosed acquired severe aplastic anemia
      (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA),
      methylprednisolone (Mpred), granulocyte colony-stimulating factor (G-CSF) as
      first-line therapy. The median age was 34 (range, 17-72) and median neutrophil
      count 0.280 x 10(9)/L. Trilineage hematologic recovery (at a median interval of
      105 days from treatment) was seen in 46 patients (37 complete, 9 partial) after
      one (n = 38) or two (n = 8) courses of ALG. Cytogenetic abnormalities were
      observed in three unresponders, clonal hematologic disease in three complete
      responders, and relapse of marrow aplasia in four complete responders. Median
      follow up for surviving patients was 1,668 days (range, 237-4,012). The actuarial
      survival at 5 years was 82%, falling to 77.1% at 7 years and was stationary at 7
      and 8 years. Survival was not influenced by the neutrophil count (72% vs. 87%,
      for neutrophils less than vs. greater than 0.2 x 10(9)/L; P = 0.54).
      Immunosuppressive treatment of SAA with the 4-drug combination appears to be
      effective. The significant prognostic effect of an enduring increase of the white
      blood cell (WBC) count during G-CSF treatment may suggest complete and partial
      response to therapy. In nonresponders, the WBC count either did not change or
      elevated values gradually returned to nearly their initial levels while the
      patients were still under G-CSF treatment. In patients not responsive to
      treatment but living under CyA and G-CSF, the possibility of developing
      cytogenetic abnormalities does not seem to be low, despite the absence of
      findings attributable to manifest myelodysplastic syndrome.

PMID- 17506069
TI  - Hepatic veno-occlusive disease after tranexamic acid administration in patients
      undergoing allogeneic hematopoietic stem cell transplantation.
AB  - Tranexamic acid is one of the widely used antifibrinolytic agents. In spite of
      its effective inhibitory activity against plasminogen, thromboembolic adverse
      events caused by tranexamic acid are rare. We encountered three recipients of
      allogeneic hematopoietic stem cell transplantation (HSCT) who developed hepatic
      veno-occlusive disease (VOD) shortly after the administration of tranexamic acid.
      Hepatic VOD was resolved completely in all patients with the discontinuation of
      the drug, and with supportive measures with or without intravenous tissue
      plasminogen activator administration. These findings suggest that administration
      of tranexamic acid could be one of the possible risk factors for developing
      hepatic VOD in HSCT recipients.

PMID- 17506071
TI  - Streptococcus pneumoniae sepsis in concurrently diagnosed multiple myeloma.

PMID- 17506072
TI  - Retracted: Effect of meso-dihydroguaiaretic acid from Machilus thunbergii Sieb et
      Zucc on MMP-1 expression in heat shock-induced cultured primary human
      fibroblasts. (Phytother Res 2006; 20(8): 714-716).

PMID- 17506073
TI  - Retracted: Matrix metalloproteinase-1 expression inhibitory compound from the
      whole plants of Viola ibukiana Makino. (Phytother Res 2005; 19(3): 239-242).

PMID- 17506074
TI  - Screening adult survivors of childhood cancer with the distress thermometer: a
      comparison with the SCL-90-R.
AB  - As the number of cancer survivors continues to grow, identification of brief,
      valid psychological screening measures will be a critical step in providing them
      with appropriate psychosocial care. The distress thermometer (DT) is a one-item
      distress screening that is recommended by the National Comprehensive Cancer
      Network (NCCN) for screening cancer patients, but has not been evaluated for
      cancer survivors. This study evaluated the validity of the DT compared to the
      Symptom Checklist-90-Revised (SCL-90-R) in a sample of 119 adult survivors of
      childhood cancer aged 18-45 (median=23.5). Results indicated that when using the
      NCCN suggested cut-off score of 5, the DT only identified 20 of the 36 SCL-90-R
      positive cases of psychological distress (sensitivity 55.6%; specificity 80.7%).
      Using an alternative DT cut-off score of 4 identified 23 of the 36 SCL-90-R
      positive cases (sensitivity 63.9%; specificity 65.1%). Receiver operating
      characteristics analysis indicated that the DT had only fair diagnostic utility
      relative to the SCL-90-R (AUC=0.72). Results do not support the validity of the
      DT in adult survivors of childhood cancer.

PMID- 17506075
TI  - Statutory reform is associated with improved court practice: results of a tri
      state comparison.
AB  - PURPOSE: This study investigates the impact of statutory reform in adult
      guardianship on court practice. METHODS: Case files for 298 cases of adult
      guardianship were reviewed in three states with varying degrees of statutory
      reform: MA (no reform), PA (major amendments in 1992), and CO (full re-enactment
      of statute per UGPPA in 2000). Five court practices associated with progressive
      statutory reform were studied: (1) diversion to less restrictive alternatives;
      (2) minimal and appropriate use of emergency procedures; (3) presence of the
      alleged incapacitated person at the hearing; (4) use of functional evaluation;
      (5) use of limited orders. RESULTS: CO more frequently utilized all five
      practices, whereas PA used diversion to less restrictive alternatives and less
      frequent emergency procedures, but not other practices. MA files rarely showed
      evidence for use of any of these reforms. IMPLICATIONS: Statutory reform may
      improve court practice. More study of the effects of reform on court practices,
      and the vulnerable adults served by these courts, is needed.

PMID- 17506076
TI  - Decision-making capacity in elderly, terminally ill patients with cancer.
AB  - Despite the importance and complexity of evaluating decision-making capacity at
      the end of life, little research has focused on terminally ill patients' decision
      making ability. The purpose of this study was to explore the decision-making
      capacity of elderly, terminally ill patients and the psychological and physical
      factors that affect decision making. Decision-making capacity and cognitive
      abilities were assessed using four measures: the Hopkins Competency Assessment
      Kit, the Bechara Gambling Task, the Concept Assessment Kit, and the Mini Mental
      Status Exam. In addition, symptoms of depression, level of physical functioning,
      and extent of physical symptoms were evaluated in order to identify correlates of
      decision-making ability. Two samples were compared: elderly, terminally ill
      patients with cancer (n = 43) and elderly, physically healthy adults living in
      supportive community residence (n = 35). Results revealed significantly poorer
      decision-making abilities among the terminal ill sample compared with healthy
      comparisons, but no association between demographic variables (e.g., age, race,
      or education) or clinical variables (depression or physical symptoms) and
      decision making. Implications for evaluating decision-making capacity are
      addressed.

PMID- 17506077
TI  - Deconstructing spiritual well-being: existential well-being and HRQOL in cancer
      survivors.
AB  - We demonstrate the utility of partitioning the spiritual well-being (SpWB)
      construct into spiritual and religious components using results from a study of
      the relationship of existential well-being to health-related quality of life
      (HRQOL) in a sample of 237 cancer survivors. Existential and religious well-being
      were measured using the FACIT-Sp-12 and HRQOL was measured using the mental and
      physical component scores of the SF-12. In hierarchical linear regression
      analyses, existential well-being fully mediated religious well-being's effect on
      HRQOL and explained unique variance in both the mental and physical HRQOL
      domains, controlling for demographic, disease, and psychosocial variables
      previously shown to impact HRQOL. Religious well-being was not predictive of
      HRQOL.

PMID- 17506078
TI  - Targeting of the mouse Slc39a2 (Zip2) gene reveals highly cell-specific patterns
      of expression, and unique functions in zinc, iron, and calcium homeostasis.
AB  - Fourteen members of the Slc39a superfamily of metal ion uptake transporters have
      been identified in mice and humans, but the physiological functions of most
      remain obscure. Herein, we created mice with Zip2 (Slc39a2) genes in which the
      open reading frame was replaced with that of the enhanced green fluorescent
      protein (EGFP), to study temporal and spatial patterns of Zip2 gene expression
      and examine the physiological roles of this transporter. Expression of this gene
      was remarkably cell-type specific and developmentally regulated in pericentral
      hepatocytes, developing keratinocytes, and a subset of immature dendritic cells
      in the immune system. In addition, the Zip2 gene was transiently expressed in
      giant trophoblast cells in the placenta. Although the Zip2 gene was not essential
      under conditions of normal dietary zinc, it played an important role in adapting
      to dietary zinc deficiency during pregnancy, and in the homeostasis of iron in
      the liver as well as iron and calcium in developing embryos. These studies
      suggest that active expression of the Zip2 gene in these few specific cell types,
      aforementioned, plays a particularly important role during zinc deficiency. These
      studies further reveal novel interactions between zinc transporter function and
      the homeostasis of other essential metals.

PMID- 17506079
TI  - Prevalence and utility of DSM-IV eating disorder diagnostic criteria among youth.
AB  - OBJECTIVE: To examine the prevalence and utility of DSM-IV eating disorder (ED)
      criteria and anorexia (AN), bulimia (BN), and binge eating disorder (BED) among
      adolescents. METHOD: An ethnically diverse population-based sample of 4,746
      public middle and high school students completed anthropometric measures and
      Project EAT survey items. RESULTS: Many youth endorsed body shape perception
      disturbance (41.5% female; 24.9% male), undue influence of body shape/weight on
      self-esteem (36.4% female; 23.9% male), and compensatory behavior (9.4% female;
      13.5% male). Prevalence among females and males, respectively, was: AN = 0.04%,
      0%; BN = 0.3%, 0.2%; BED = 1.9%, 0.3%. Analyses of individual criteria showed
      high sensitivity and negative predictive values for each disorder and
      corresponding criteria, low specificity for several AN (27.8%) and BN (32.0%)
      criteria, and low positive predictive values (0.06-40.2%). CONCLUSION: Body
      disparagement and compensatory behaviors indicate eating disturbance, despite low
      prevalence of EDs. Diagnostic classification may be clinically useful, but is
      complicated for use in epidemiological populations.

PMID- 17506080
TI  - Childhood abuse and eating disorders in gay and bisexual men.
AB  - OBJECTIVE: This study examines the association between eating disorders and a
      history of childhood abuse in gay and bisexual men, and how substance abuse and
      depression might impact this relationship. METHOD: 193 white, black, Latino gay,
      and bisexual men were sampled from community venues. DSM-IV diagnoses of
      anorexia, bulimia, and binge eating disorder were assessed using the World Health
      Organization's Composite International Diagnostic Interview. RESULTS: Men with a
      history of childhood sexual abuse are significantly more likely to have
      subclinical bulimia or any current full-syndrome or subclinical eating disorder
      compared with men who do not have a history of childhood sexual abuse. A history
      of depression and/or substance use disorders did not mediate this relationship.
      CONCLUSION: Researchers should study other potential explanations of the
      relationship between a history of childhood abuse and eating disorders in gay and
      bisexual men. Clinicians working with gay and bisexual men who have a history of
      childhood abuse should assess for disordered eating as a potential mechanism to
      cope with the emotional sequelae associated with abuse.

PMID- 17506081
TI  - Predicting PSA response of prostate cancer to radiation therapy with Doppler
      sonography.
AB  - OBJECTIVE: We report a prospective investigation of the correlation between
      pretreatment Doppler vascular density (DVD) of the entire prostate gland and
      subsequent prostate-specific antigen (PSA) response following external beam
      radiation therapy, for patients with low- or intermediate-risk prostate cancer.
      This report updates a previous report (Sehgal et al., Acad Radiol 2003;10:366)
      with longer patient follow-up and additional quantitative and clinically relevant
      end points. METHODS: Before radiation therapy, we imaged 12 patients with
      transrectal Doppler sonography and measured the mean DVD of the prostate for
      each. For analysis, patients were separated into 3 groups by low, intermediate,
      and high DVD. The mean DVD for each group was linearly correlated with mean
      values for time above a PSA threshold of 1.0 ng/ml, post-therapy plateau PSA, and
      nadir PSA. RESULTS: We previously observed that pretreatment mean DVD had a
      strong inverse correlation with initial rate of post-therapy decline in PSA. With
      substantially longer follow-up on the same cohort of patients (median, 52
      months), we now observe that pretreatment mean DVD also correlates with post
      therapy nadir PSA (R = 0.94) and with time above a PSA threshold of 1.0 ng/mL (R
      = 0.99). CONCLUSION: The results of the current study are consistent with our
      earlier suggestion that pretreatment measurement of DVD of the entire prostate
      gland may be a clinically useful prognostic indicator in early prostate cancer
      treated with radiation. However, additional data from larger numbers of patients
      are needed to draw firm conclusions.

PMID- 17506082
TI  - Effect of variability in anatomical landmark location on knee kinematic
      description.
AB  - Small variability associated with identifying and locating anatomical landmarks
      on the knee has the potential to affect the joint coordinate systems and reported
      kinematic descriptions. The objectives of this study were to develop an approach
      to quantify the effect of landmark location variability on both tibiofemoral and
      patellofemoral kinematics and to identify the critical landmarks and associated
      degrees of freedom that most affected the kinematic measures. The commonly used
      three-cylindric open-chain kinematic description utilized measured rigid body
      kinematics from a cadaveric specimen during simulated gait. A probabilistic
      analysis was performed with 11 anatomical landmarks to predict the variability in
      each kinematic. The model predicted the absolute kinematic bounds and offset
      kinematic bounds, emphasizing profile shape, for each kinematic over the gait
      cycle, as well as the range of motion. Standard deviations of up to 2 mm were
      assumed for the anatomical landmark locations and resulted in significant
      variability in clinically relevant absolute kinematic parameters of up to 6.5
      degrees and 4.4 mm for tibiofemoral and 7.6 degrees and 6.5 mm for patellofemoral
      kinematics. The location of the femoral epicondylar prominences had the greatest
      effect on both the tibiofemoral and patellofemoral kinematic descriptions. A
      quantitative understanding of the potential changes in kinematic description
      caused by anatomical landmark variability is important not only to the accuracy
      of kinematic gait studies and the evaluation of total knee arthroplasty implant
      performance, but also may impact component placement decision-making in computer
      assisted surgery.

PMID- 17506083
TI  - Comparing two independent incidence rates using conditional and unconditional
      exact tests.
AB  - Several unconditional exact tests, which are constructed to control the Type I
      error rate at the nominal level, for comparing two independent Poisson rates are
      proposed and compared to the conditional exact test using a binomial
      distribution. The unconditional exact test using binomial p-value, likelihood
      ratio, or efficient score as the test statistic improves the power in general,
      and are therefore recommended. Unconditional exact tests using Wald statistics,
      whether on the original or square-root scale, may be substantially less powerful
      than the conditional exact test, and is not recommended. An example is provided
      from a cardiovascular trial.

PMID- 17506084
TI  - The perceived credibility of older adults as witnesses and its relation to
      ageism.
AB  - In experiment 1, 267 undergraduates read a case summary and witness statement.
      Sex and age of the witness (49, 69, 79 or 89 years) were varied. Participants
      rated the witness's perceived convincingness, confidence, quality of observation,
      accuracy, honesty, competence, memory, suggestibility, and cognitive functioning.
      As well as an age effect for honesty, age by sex interactions were observed for
      several characteristics, particularly for comparisons of the 79-year-olds versus
      the 49-year-olds, and 89-year-olds versus the 49-year-olds. In experiment 2, 94
      undergraduates read the same testimony given by a 79-year-old male or female
      witness, and completed the Fraboni Scale of Ageism and the Aging Semantic
      Differential. Participants who evidenced stronger aging stereotypes on these
      measures rated the witness less favorably than did participants who were less
      prejudiced. This experiment is the first to show a link between perceived
      credibility of older adults and ageist attitudes. Practical applications
      regarding how older witnesses are viewed by jurors, and the criminal justice
      system more generally, are discussed.

PMID- 17506085
TI  - Gray, black, and blue: the state of research and intervention for intimate
      partner abuse among elders.
AB  - Though not as common as in younger populations, intimate partner abuse (IPA)
      among elders is a significant and often overlooked problem. In this article, we
      focus on problems for research and intervention. We begin with a brief review of
      the phenomena of elder abuse and IPA, highlighting problems resulting from
      definitional issues and inconsistencies in research methodology. The balance of
      the paper comprises a discussion of problems for intervention. Drawing from the
      IPA and elder abuse literatures, risk factors unique to IPA among elders are
      presented, and limitations of existing screening and risk assessment instruments
      for use within this context are identified. The focus then shifts to legal
      considerations when working with elders who have experienced or perpetrated IPA.
      Our goals are to synthesize the elder abuse and IPA literatures, identify
      limitations within both, and to reflect upon the state of knowledge regarding IPA
      among elders.

PMID- 17506086
TI  - Constructing insanity: jurors' prototypes, attitudes, and legal decision-making.
AB  - Research consistently indicates that jurors' intuitive prototypes of insanity and
      case-relevant attitudes shape their verdicts more strongly than legal definitions
      of insanity. Based on a sample of 113 prospective jurors, this study was designed
      to (a) assess the extent to which three prototypes of insanity held by jurors in
      a past study generalize to a sample of jurors in another state and (b) determine
      the relative influence of attitudes toward the insanity defense and prototypes of
      insanity on jurors' case judgments across four insanity case vignettes. Results
      suggest that jurors' attitudes toward the insanity defense affected case
      judgments so strongly (r = .41-.61) that they swamped efforts to assess jurors'
      prototypes of insanity. Further, jurors' prototypes of insanity offered little
      incremental utility beyond that of insanity defense attitudes. Implications for
      identifying biased jurors and potential interventions for bringing jurors'
      decisions into greater accord with the law are discussed.

PMID- 17506087
TI  - Generation of a floxed allele of the mouse Endoglin gene.
AB  - Endoglin is an auxiliary receptor for TGFbeta signalling. Heterozygous germline
      Endoglin mutations have been identified in patients with the vascular
      abnormality, Hereditary Haemorrhagic Telangiectasia. Endoglin is upregulated in
      endothelial cells during angiogenesis and loss of Endoglin in the mouse results
      in embryonic lethality at mid-gestation. This phenotype points to an important
      role of Endoglin in new blood vessel formation but precludes analysis at later
      stages in development and in postnatal life. To bypass this limitation and allow
      further investigations of the function of Endoglin we have generated a floxed
      Endoglin allele in which loxP sites flank exons 5 and 6. Mice homozygous for this
      allele are normal and in the presence of appropriate Cre lines will allow time
      and cell specific Endoglin deletion for in vivo analysis of function in
      cardiovascular development and disease.

PMID- 17506088
TI  - Noncanonical cell death pathways act during Drosophila oogenesis.
AB  - Programmed cell death (PCD) is a highly conserved process that occurs during
      development and in response to adverse conditions. In Drosophila, most PCDs
      require the genes within the H99 deficiency, the adaptor molecule Ark, and
      caspases. Here we investigate 10 cell death genes for their potential roles in
      two distinct types of PCD that occur in oogenesis: developmental nurse cell PCD
      and starvation-induced PCD. Most of the genes investigated were found to have
      little effect on late stage developmental PCD in oogenesis, although ark mutants
      showed a partial inhibition. Mid-stage starvation-induced germline PCD was found
      to be independent of the upstream activators and ark although it requires
      caspases, suggesting an apoptosome-independent mechanism of caspase activation in
      mid-oogenesis. These results indicate that novel pathways must control PCD in the
      ovary.

PMID- 17506089
TI  - Cell autonomous sorting and surface positioning in the formation of primitive
      endoderm in embryoid bodies.
AB  - The differentiation and formation of the primitive endoderm in early embryos can
      be mimicked in vitro by the aggregation of embryonic stem cells to form embryoid
      bodies. We present morphological evidence that primitive endoderm cells often
      first locate in the interior of embryoid bodies and subsequently migrate to the
      surface. Cell mixing experiments indicate that surface positioning is an
      intrinsic property of endoderm epithelial cells. Moreover, Disabled-2 (Dab2) is
      required for surface sorting and positioning of the endoderm cells: when Dab2
      expression was eliminated, the differentiated endoderm epithelial cells
      distributed throughout the interior of the embryoid bodies. Surprisingly, E
      cadherin is dispensable for primitive endoderm differentiation and surface
      sorting in embryoid bodies. These results support the model that primitive
      endoderm cells first emerge in the interior of the inner cell mass and are
      subsequently sorted to the surface to form the primitive endoderm.

PMID- 17506090
TI  - Cytologic diagnosis of atypical squamous cells of undetermined significance in
      perimenopausal and postmenopausal women: lessons learned from human
      Papillomavirus DNA testing.
AB  - BACKGROUND: The authors have noted that in cervical cytology specimens from
      perimenopausal and postmenopausal women, the diagnosis of atypical squamous cells
      of undetermined significance (ASC-US), as defined in the Bethesda system, is
      often not associated with a clinically evident lesion on follow-up. Reflex human
      papillomavirus (HPV) testing provides an opportunity to distinguish cytologic
      features of significance from those within the spectrum of benign cellular change
      in this age group. METHODS: Liquid-based preparations that were diagnosed as ASC
      US between January 2003 and July 2005 at Emory University Hospital were
      identified from the computer files. The results of HPV-DNA testing were recorded.
      Two hundred four Papanicolaou tests from perimenopausal women (n = 81, 40-49
      years) and postmenopausal women (n = 123, >50 years) were reviewed in a blinded
      fashion. RESULTS: HPV-DNA results were available for 903 of 1044 patients
      diagnosed as ASC-US. Overall, 323 results (35.8%) were positive, 510 results
      (56.6%) were negative, and 70 results (7.8%) were indeterminate. In addition, 73%
      of ASC-US specimens in patients aged > or =40 years were negative for HPV DNA.
      The HPV-DNA detection rate dropped from 60% in the group ages 10 to 19 years to
      approximately 18% in the group aged >50 years. A review of HPV-negative cases in
      the group aged >40 years showed squamous cells with random nuclear enlargement
      and slight hyperchromasia that likely were interpreted as ASC-US (based on the
      cells that were dotted by the original reviewer). Nuclear grooves were frequent
      in these nuclei; and cytoplasmic halos, when present, usually were perinuclear.
      CONCLUSIONS: HPV-DNA detection in cervical cytology specimens has an inverse
      relation to patient age. A diagnosis of ASC-US in perimenopausal and
      postmenopausal women is likely to result in a negative HPV-DNA test in a
      significant proportion of patients. Enlarged nuclei with nuclear grooves and
      slight hyperchromasia are possibly the cause of ASC-US overdiagnosis in this age
      group.

PMID- 17506091
TI  - Colobomatous macrophthalmia with microcornea syndrome maps to the 2p23-p16
      region.
AB  - Colobomatous macrophthalmia with microcornea syndrome (OMIM 602499) is a rare,
      autosomal dominant malformation characterized by microcornea, uveal coloboma,
      axial enlargement of the globe, and myopia. Using what is currently the largest
      described pedigree and candidate localization approach, we first excluded the
      candidate genes PAX2, PAX3, PAX6, and PAX9. Subsequently, the chromosome 14q24
      region containing the CHX10, SIX1, and SIX4 genes were also excluded. Positive
      LOD scores were obtained with the DNA markers selected from the 2p23-p16 region.
      A maximum pairwise LOD score of 3.61 (Theta = 0) was noted with the DNA marker
      D2S1788. Haplotype analysis positioned the locus between DNA markers D2S2263 and
      D2S1352 within a 22 Mb physical interval. This region contains major candidate
      genes, such as SIX2, SIX3, and CYP1B1; however, mutation analysis did not
      identify a causative mutation in these genes. Macrophthalmia, colobomatous, with
      microcornea (MACOM) is proposed as the gene symbol for this malformation linked
      to 2p23-p16.

PMID- 17506092
TI  - Comprehensive EMX2 genotyping of a large schizencephaly case series.
AB  - Schizencephaly is a brain malformation disorder characterized by one or more full
      thickness clefts through the cerebral cortex. While initial reports suggested
      that EMX2 mutations are a common cause of schizencephaly, more recent evidence
      suggests that EMX2 mutations are not a common cause of this malformation. To
      determine the frequency of EMX2 mutations in patients with schizencephaly, we
      sequenced EMX2 in a cohort of 84 affected probands. No pathologic mutations were
      identified in this cohort, suggesting that EMX2 mutations are an uncommon cause
      of schizencephaly.

PMID- 17506093
TI  - Oculo-auriculo-vertebral spectrum: associated anomalies, functional deficits and
      possible developmental risk factors.
AB  - Swedish patients with the oculo-auriculo-vertebral (OAV) spectrum participated in
      a prospective multidisciplinary investigation. The aims of the study were to
      describe their systemic and functional defects, especially autism spectrum
      disorders, and to search for possible etiologic risk factors. Available medical
      records were studied and the mothers answered a questionnaire on history of
      prenatal events. A clinical examination evaluating systemic findings, vision,
      hearing, speech, oral and swallowing function, and neuropsychiatric function,
      especially autism, was made. Eighteen patients, (11 males, 7 females) aged 8
      months to 17 years with OAV were studied. Most frequent systemic malformations
      included, ear abnormalities (100%), ocular malformations (72%), vertebral
      deformities (67%), cerebral anomalies (50%), and congenital heart defects (33%).
      Functional defects consisted of hearing impairment (83%), visual impairment
      (28%), both visual and hearing impairment (28%), difficulties in feeding/eating
      (50%), speech (53%), mental retardation (39%), and severe autistic symptoms
      (11%). Three children were born following assisted fertilization (two
      intracytoplasmatic sperm injection, one in vitro fertilization), two mothers
      reported early bleedings, and six (33%) mothers had smoked during pregnancy.

PMID- 17506094
TI  - dup(8p)/del(8q) recombinant chromosome in a girl with hepatic focal nodular
      hyperplasia.
AB  - A 15-year-old girl had exertion dyspnea, focal nodular hyperplasia of the liver,
      portal vein hypoplasia, portopulmonary hypertension, mental retardation, and
      minor facial abnormalities. Cytogenetic analysis demonstrated an abnormal
      chromosome 8 with 8p22-pter duplication and 8q24.3-qter deletion, with the
      duplicated 8p segment attached to band 8q24.3. Her mother had a pericentric
      inversion of chromosome 8, inv(8)(p22q24.3). Therefore, the girl's abnormal
      chromosome 8 was a recombinant of maternal inversion chromosome:
      46,XX,rec(8)dup(8p)inv(8)(p22q24.3)mat. Further characterization of the
      recombinant chromosome, using array CGH and regional FISH analyses, defined 15 Mb
      distal 8p duplication and 0.5 Mb 8q deletion. Possible correlation of the
      recombinant chromosome and hepatic focal nodular hyperplasia in the patient is
      discussed.

PMID- 17506095
TI  - Chorea associated with antiphospholipid antibodies in a patient with Kabuki
      syndrome.
AB  - Kabuki syndrome, OMIM 147920 (KS) is a disorder characterized by multi-system
      abnormalities. These include physical, neurological, endocrine, and autoimmune
      abnormalities. Multiple autoimmune abnormalities are described in KS such as
      immune thrombocytopenic purpura (ITP), vitiligo, thyroiditis, hemolytic anemia,
      and hypogammaglobulinemia. In this report, we describe a patient with KS with
      sudden onset chorea associated with the presence of anti-phospholipid antibodies
      (aPLs) in the serum. Chorea in the presence of aPLs has been well described in
      the literature both in the presence and absence of antiphospholipid syndrome
      (APS) and systemic lupus erythematosus (SLE). This report of APL in a patient
      with KS adds to the list of autoimmune disorders seen in patients with KS and
      also strengthens the hypothesis that patients with this syndrome have an
      increased incidence of immune dysregulation.

PMID- 17506096
TI  - Fortuitous FISH diagnosis of an interstitial microdeletion (5)(q31.1q31.2) in a
      girl suspected to present a cri-du-chat syndrome.
AB  - Constitutional interstitial deletions of 5q are relatively rare and most are
      poorly characterized cytogenetically. Consequently a definite karyotype-phenotype
      correlation is difficult to establish. We report on a new case of a girl
      presenting with an abnormal cry, upslanting palpebral fissures, hypertelorism,
      anteverted nostrils, microretrognathia, growth retardation, and an adenoid cyst
      at the base of the tongue. The first suspected diagnosis was cri-du-chat syndrome
      because of the mewing cry. Standard cytogenetic analyses were interpreted as
      normal, but FISH studies using the probe of cri-du-chat syndrome with the control
      probe EGR1 (5q31.2)/D5S23 (Abbott) revealed a 5q31.2 microdeletion which was then
      confirmed by CGH-array (Abbott). FISH studies using PACs and BACs clones (Rocchi,
      Italia) enabled us to characterize the breakpoints of the deleted region.
      Cytogenetic analysis with FISH studies revealed a normal karyotype with normal
      5q31 region in both parents. This case is compared with the other cases reported
      in the literature.

PMID- 17506097
TI  - Detection of a de novo interstitial 2q microdeletion by CGH microarray analysis
      in a patient with limb malformations, microcephaly and mental retardation.
AB  - We describe the cytogenetic diagnosis using BAC- and oligonucleotide microarrays
      of a 16-year-old Laotian-American female, who first presented at 2 1/2 years of
      age with microcephaly, developmental retardation, and skeletal abnormalities of
      the upper limb including mild syndactyly of the second and third and the third
      and fourth fingers, short middle phalanges and clinodactyly of the fifth digit at
      the distal interphalangel joint on both hands, and symphalangism of the
      metacarpal-phalangeal joints of the second and fifth digits bilaterally. Her
      lower limbs displayed symphalangism of the metatarsal-phalangeal joint of the
      second, third, and fourth digits on both feet, with fusion of the middle and
      distal phalanges of the second and fifth digits and hallux valgus bilaterally. G
      banded chromosomal study at age 4 was normal. However, comparative genomic
      hybridization at age 15 with the Spectral Genomics 1 Mb Hu BAC array platform
      indicated a microdeletion involving two BAC clones, RP11-451F14 --> RP11-12N7 at
      2q31.1. The maximal deletion on initial analysis comprised the HOXD cluster,
      which is implicated in limb development. Fluorescence in situ hybridization
      (FISH) using the RP11-451F14 probe confirmed the deletion. Both parents were
      negative for the deletion. Additional FISH using BAC RP11-387A1, covering the
      HOXD cluster, limited the maximal deletion to approximately 2.518 Mb, and
      excluded involvement of the HOXD cluster. The Agilent 44K and 244K platforms
      demonstrated a deletion of approximately 2,011,000 bp, which did not include the
      HOXD cluster. The malformations in our patient may be caused by deletion of a
      regulatory element far upstream of the HOXD cluster.

PMID- 17506098
TI  - Fetal and maternal CYP2E1 genotypes and the risk of nonsyndromic oral clefts.

PMID- 17506099
TI  - A newly recognized craniosynostosis syndrome with features of Aarskog-Scott and
      Teebi syndromes.
AB  - We present two unrelated boys with craniosynostosis and similar facial features
      including hypertelorism, down-slanted palpebral fissures, ptosis, broad mouth
      with a thin upper lip, and preauricular pits. Both patients had short, broad
      first digits as well as short, broad hands. Both also had respiratory
      difficulties and umbilical abnormalities. Although, many of these features are
      seen in Aarskog-Scott and in Teebi hypertelorism syndromes, both children had
      craniosynostosis, which has not been previously reported in either syndrome. We
      propose that these children may have a previously unreported syndrome consistent
      with X-linked inheritance, although an autosomal dominant mode of transmission
      cannot be excluded.

PMID- 17506100
TI  - Interstitial deletion of 6q without phenotypic effect.
AB  - Cytogenetically detectable euchromatic deletions without phenotypic consequences
      are rarely encountered. We report on a 34-year-old woman with normal intelligence
      referred for karyotyping because of recurrent abortions. With the exception of a
      bicuspid aortic valve without hemodynamic consequences, which is a common minor
      anomaly in the general population, no dysmorphic features were found on physical
      examination. Conventional chromosome analysis (GTG-banding) revealed an
      interstitial deletion in the long arm of chromosome 6. With array comparative
      genomic hybridization (array-CGH) the size of the deletion was estimated to be
      between 9.9 and 11.6 Mb and the refined karyotype was 46,XX,del(6)(q22.31q23.1).

PMID- 17506101
TI  - Genetic drift. Physiologic noise obscures genotype-phenotype correlations.

PMID- 17506102
TI  - Associations of osseous abnormalities in Neurofibromatosis 1.
AB  - The characteristic sites of Neurofibromatosis 1-associated osseous manifestations
      are the long bones (usually the tibia and fibula), vertebrae and sphenoid wing.
      Although these focal bony lesions may cause profound clinical consequences, a
      minority of people with NF1 are affected. However, most people with NF1 are
      shorter than expected for their age, gender and family. The pathogenesis of NF1
      focal osteopathy and its relationship, if any, to short stature are unknown. We
      examined associations between the occurrence of various osseous lesions in 3377
      NF1 probands from the Children's Tumor Foundation NF International Database.
      Using logistic regression analysis among 260 NF1 probands who had undergone
      radiological examination of both the spine and skull, we found associations
      between the occurrence of sphenoid wing and long bone osteopathy (conditional
      odds ratio [OR] = 6.1; 95% confidence interval [CI] = 1.7-22.3; P = 0.006) and
      between sphenoid wing and vertebral osteopathy (OR = 16.9; 95% CI = 5.3-53.3; P <
      0.001) after adjusting for age and gender. Similar findings were observed from
      all 3377 NF1 probands using a multivariate probit regression model. In a separate
      analysis, we found lower age- and gender-standardized height in patients who had
      characteristic vertebral or sphenoid wing lesions than in people who did not (P <
      0.05). We found no relationship between height and tibial osteopathy. We conclude
      that some people with NF1 are more likely to develop osseous manifestations than
      others and speculate that there may be a common pathogenetic mechanism
      responsible for the development of osseous abnormalities and that of the
      vertebrae and long bones.

PMID- 17506103
TI  - DNA demethylation reactivation of imprinted genes in cell lines from patients
      with Prader-Willi syndrome and a mouse model.

PMID- 17506105
TI  - Report of a child with a complete de novo 17p duplication localized to the
      terminal region of the long arm of chromosome 17.
AB  - We report the second case of a child with trisomy of the entire short arm of
      chromosome 17 secondary to a de novo duplication. Trisomy 17p in this patient
      resulted from a duplication, localized to the distal region of the long arm of
      the same chromosome, an abnormality not previously described. This cytogenetic
      abnormality was confirmed using whole chromosome paint, subtelomeric and Smith
      Magenis probes by fluorescence in situ hybridization (FISH) analysis. The child
      presented with phenotypic features previously described in trisomy 17p, including
      some specific facial dysmorphia, microcephaly, growth retardation, hypotonia,
      short webbed neck, congenital heart defect, minor abnormalities of the hands,
      agenesis of the corpus callosum and abnormalities of the iris. Iris alterations
      and defects involving the left side of heart and the aorta also may represent
      truly clinical hallmarks of this cytogenetic abnormality. In conclusion, this
      cytogenetic anomaly seems to represent a severe malformation entity with a poor
      prognosis and a recognizable clinical pattern that justifies the use of the term
      "17p trisomy syndrome" suggested previously by other authors.

PMID- 17506106
TI  - The PDAC syndrome (pulmonary hypoplasia/agenesis, diaphragmatic
      hernia/eventration, anophthalmia/microphthalmia, and cardiac defect) (Spear
      syndrome, Matthew-Wood syndrome): report of eight cases including a living child
      and further evidence for autosomal recessive inheritance.
AB  - The combination of pulmonary agenesis/dysgenesis/hypoplasia,
      microphthalmia/anophthalmia, and a diaphragmatic defect (agenesis or eventration)
      is a rare syndrome presumed to have an autosomal recessive mode of inheritance
      based on a report of affected siblings born to unaffected parents [Seller et al.,
      1996]. The condition is known as Spear syndrome and Matthew-Wood syndrome,
      although genetic heterogeneity cannot be ruled out. We report on eight patients
      with this condition including a living child, three sibs and three isolated
      cases. Most presented with fetal ultrasound findings of
      microphthalmia/anophthalmia, and diaphragmatic eventration/hernia and in five,
      cardiac abnormalities were also found. The earliest detection was at 20 weeks
      gestation. This is the second report of sibs affected with this condition, which
      supports an autosomal recessive mode of inheritance. We present the first and
      only reported living patient with this condition and expand the intrafamilial,
      interfamilial, and ethnic variability of this condition. We suggest changing the
      condition's name to PDAC to reflect the most important components of this
      condition.

PMID- 17506107
TI  - Expanding spectrum of congenital disorder of glycosylation Ig (CDG-Ig): sibs with
      a unique skeletal dysplasia, hypogammaglobulinemia, cardiomyopathy, genital
      malformations, and early lethality.
AB  - In this report, we describe a brother and sister who presented at birth with
      short-limb skeletal dysplasia, polyhydramnios, prematurity, and generalized
      edema. Dysmorphic features included broad nose, thick ears, thin lips,
      micrognathia, inverted nipples, ulnar deviation at the wrists, spatulate fingers,
      fifth finger camptodactyly, nail hypoplasia, and talipes equinovarus. Other
      features included short stature, microcephaly, psychomotor retardation, B-cell
      lymphopenic hypogammaglobulinemia, sensorineural deafness, retinal detachment and
      blindness, intestinal malrotation with poor gastrointestinal motility, persistent
      hyponatremia, intermittent hypoglycemia, and thrombocytopenia. Cardiac anomalies
      included PDA, VSD, hypertrophic cardiomyopathy, and arrhythmias. The brother had
      a small penis with hypospadias, hypoplastic scrotum, and non-palpable testes.
      Skeletal findings included absent ossification of cervical vertebral bodies,
      pubic bones, knee epiphyses, and tali. Both sibs died before age 2 years, one of
      overwhelming sepsis and the other of cardiorespiratory failure associated with
      her cardiomyopathy. Metabolic studies showed a type 1 pattern of abnormal serum
      transferrin glycosylation. Fibroblasts synthesized truncated LLOs, primarily
      Man(7)GlcNAc(2), suggestive of CDG-Ig. Both sibs were compound heterozygotes for
      a novel 301 G > A (G101R) mutation and a previously described 437 G > A (R146Q)
      mutation in ALG12. Congenital disorders of glycosylation should be considered for
      children with undiagnosed multi-system disease including neurodevelopmental
      delay, skeletal dysplasia, immune deficiency, male genital hypoplasia, and
      cardiomyopathy.

PMID- 17506108
TI  - Chromosomal microarray analysis (CMA) detects a large X chromosome deletion
      including FMR1, FMR2, and IDS in a female patient with mental retardation.
AB  - Chromosomal microarray analysis (CMA) by array-based comparative genomic
      hybridization (CGH) is a new clinical test for the detection of well
      characterized genomic disorders caused by chromosomal deletions and duplications
      that result in gene copy number variation (CNV). This powerful assay detects an
      abnormality in approximately 7-9% of patients with various clinical phenotypes,
      including mental retardation. We report here on the results found in a 6-year-old
      girl with mildly dysmorphic facies, obesity, and marked developmental delay. CMA
      was requested and showed a heterozygous loss in copy number with clones derived
      from the genomic region cytogenetically defined as Xq27.3-Xq28. This loss was not
      cytogenetically visible but was seen on FISH analysis with clones from the
      region. Further studies confirmed a loss of one copy each of the FMR1, FMR2, and
      IDS genes (which are mutated in Fragile X syndrome, FRAXE syndrome, and Hunter
      syndrome, respectively). Skewed X-inactivation has been previously reported in
      girls with deletions in this region and can lead to a combined Fragile X/Hunter
      syndrome phenotype in affected females. X-inactivation and iduronate 2-sulfatase
      (IDS) enzyme activity were therefore examined. X-inactivation was found to be
      random in the child's peripheral leukocytes, and IDS enzyme activity was
      approximately half of the normal value. This case demonstrates the utility of CMA
      both for detecting a submicroscopic chromosomal deletion and for suggesting
      further testing that could possibly lead to therapeutic options for patients with
      developmental delay.

PMID- 17506110
TI  - Molecular characterization of the PEX5 gene encoding peroxisomal targeting signal
      1 receptor from the methylotrophic yeast Pichia methanolica.
AB  - In this study, we describe the molecular characterization of the PEX5 gene
      encoding the peroxisomal targeting signal 1 (PTS1) receptor from the
      methylotrophic yeast Pichia methanolica. The P. methanolica PEX5 (PmPEX5) gene
      contains a open reading frame corresponding to a gene product of 646 amino acid
      residues, and its deduced amino acid sequence shows a high similarity to those of
      Pex5ps from other methylotrophic yeasts. Like other Pex5ps, the PmPex5p possesses
      seven repeats of the TPR motif in the C-terminal region and three WXXXF/Y motifs.
      A strain with the disrupted PEX5 gene (pex5Delta) lost its ability to grow on
      peroxisome-inducible carbon sources, methanol and oleate, but grew normally on
      glucose and glycerol. Disruption of PmPEX5 caused a drastic decrease in
      peroxisomal enzyme activities and mislocalization of GFP-PTS1 and some
      peroxisomal methanol-metabolizing enzymes in the cytosol. Expression of the
      PmPEX5 gene was regulated by carbon sources, and it was strongly expressed by
      peroxisome-inducible carbon sources, especially methanol. Taken together, these
      findings show that PmPex5p has an essential physiological role in peroxisomal
      metabolism of P. methanolica, including methanol metabolism, and in peroxisomal
      localization and activation of methanol-metabolizing enzymes, e.g. AOD isozymes,
      DHAS and CTA.

PMID- 17506111
TI  - Disruption of URA7 and GAL6 improves the ethanol tolerance and fermentation
      capacity of Saccharomyces cerevisiae.
AB  - Screening of the homozygous diploid yeast deletion pool of 4741 non-essential
      genes identified two null mutants (Deltaura7 and Deltagal6) that grew faster than
      the wild-type strain in medium containing 8% v/v ethanol. The survival rate of
      the gal6 disruptant in 10% ethanol was higher than that of the wild-type strain.
      On the other hand, the glucose consumption rate of the ura7 disruptant was better
      than that of the wild-type strain in buffer containing ethanol. Both disruptants
      were more resistant to zymolyase, a yeast lytic enzyme containing mainly beta-1,3
      glucanase, indicating that the integrity of the cell wall became more resistance
      to ethanol stress. The gal6 disruptant was also more resistant to Calcofluor
      white, but the ura7 disruptant was more sensitive to Calcofluor white than the
      wild-type strain. Furthermore, the mutant strains had a higher content of oleic
      acid (C18 : 1) in the presence of ethanol compared to the wild-type strain,
      suggesting that the disruptants cope with ethanol stress not only by modifying
      the cell wall integrity but also the membrane fluidity. When the cells were grown
      in medium containing 5% ethanol at 15 degrees C, the gal6 and ura7 disruptants
      showed 40% and 14% increases in the glucose consumption rate, respectively.

PMID- 17506113
TI  - In vivo MRI of submillisecond T(2) species with two-dimensional and three
      dimensional radial sequences and applications to the measurement of cortical bone
      water.
AB  - Water in dense collagenous tissues such as tendons and ligaments, as well as
      water in cortical bone that occupies the spaces of the lacuno-canicular system or
      is tightly bound to collagen, is not ordinarily detectable by MRI. Water proton
      T(2) in these structures is generally less than 1 ms. Recent advances in
      instrumentation in conjunction with non-Cartesian imaging strategies now allow
      center of k-space to be scanned 100 micros or less after excitation. We examined
      the performance of two radial pulse sequences, a 2D sequence with half-pulse
      excitation and a new 3D hybrid sequence with variable-echo Cartesian encoding in
      the third dimension, on a whole-body 3 T scanner. Both pulse sequences used long
      T(2) soft-tissue suppression pulses. The half-pulse slice profiles observed
      experimentally agreed well with those computed on the basis of a numerical
      solution of Bloch equations. The techniques yielded a signal-to-noise ratio of
      the order of 25 in 9 min scan time at a nominal voxel size of 0.58 x 0.58 x 8
      mm(3) and 50-90 micros 'echo time' in the cortex of the tibial mid-shaft. With
      the use of an external reference, the water volume fraction of cortical bone in
      four subjects (mean +/- SD age 32.25 +/- 5.3 years) was found to be 22.5 +/-
      2.7%, in good agreement with literature values.

PMID- 17506114
TI  - Doubling the resolution of echo-planar brain imaging by acquisition of two k
      space lines per gradient reversal using TRAIL.
AB  - Single-shot echo-planar imaging (EPI) is an important method for MRI of the
      brain. A method has been developed to double the resolution of EPI in the phase
      encode direction, without requiring increases in the maximum gradient amplitude
      or slew rate. The new approach is based on an EPI implementation of the TRAIL
      (two reduced acquisitions interleaved) method, in which two images, acquired in
      rapid succession, are spatially interleaved. In addition, two lines of k-space
      are acquired for each reversal of the readout gradient. Two full-length readouts
      are needed, therefore power deposition is increased and the total acquisition
      time is doubled compared with conventional EPI. However, the individual readouts
      do not increase in length, so there is no increase in image blurring, and
      distortion is halved as a result of the closer temporal spacing of the acquired k
      space lines. A correction method is also presented to remove additional potential
      Nyquist ghosting. The new method is demonstrated in vivo at 4.7 T and could in
      principle be combined with existing approaches for increasing resolution, such as
      partial Fourier or parallel imaging.

PMID- 17506115
TI  - 1H MRS identifies specific metabolite profiles associated with MYCN-amplified and
      non-amplified tumour subtypes of neuroblastoma cell lines.
AB  - Neuroblastoma is the most common extracranial solid malignancy in children. The
      disease possesses a broad range of clinical phenotypes with widely varying
      prognoses. Numerous studies have sought to identify the associated genetic
      abnormalities in the tumour, resulting in the identification of useful prognostic
      markers. In particular, the presence of multiple copies of the MYCN oncogene
      (referred to as MYCN amplification) has been found to confer a poor prognosis.
      However, the molecular pathways involved are as yet poorly defined. Metabolite
      profiles generated by in vitro (1)H MRS provide a means of investigating the
      downstream metabolic consequences of genetic alterations and can identify
      potential targets for new agents. Thirteen neuroblastoma cell lines possessing
      multiple genetic alterations were investigated; seven were MYCN amplified and six
      MYCN non-amplified. In vitro magic angle spinning (1)H MRS was performed on cell
      suspensions, and the spectra analysed to obtain metabolite concentration ratios
      relative to total choline (tCho). A principal component analysis using these
      concentration ratios showed that MYCN-amplified and non-amplified cell lines form
      separate classes according to their metabolite profiles. Phosphocholine/tCho and
      taurine/tCho were found to be significantly raised (p < 0.05) and
      glycerophosphocholine/tCho significantly reduced (p < 0.05) in the MYCN-amplified
      compared with the MYCN non-amplified cell lines (two-tailed t test). (1)H MRS of
      the SH-EP1 cell line and an isogenic cell line transfected with the MYCN oncogene
      also showed that MYCN oncogene over-expression causes alterations in
      phosphocholine, glycerophosphocholine and taurine concentrations. Molecular
      pathways of choline and taurine metabolism are potential targets for new agents
      tailored to MYCN-amplified neuroblastoma.

PMID- 17506116
TI  - Senile EBV-associated B-cell lymphoproliferative disorder of prepatellar bursa in
      an elderly patient with multifocal urate arthropathy.
AB  - We report a case of an EBV-associated high grade B-cell lymphoproliferative
      disorder occurring in the synovial membrane of an elderly patient with gout
      arthropathy. The EBV-infected B-cells displayed a pattern of viral gene
      expression (EBNA2+/LMP1+) typically seen during primary EBV-infection and in
      lymphoproliferations occurring in immunosuppressed individuals. This case
      conforms to senile EBV-associated lymphoproliferative disorders previously
      reported only in Japanese patients. We suggest that an impaired EBV-specific T
      cell immunity, local or systemic, may play a role in the development of this
      disorder and that chronic diseases such as gout may be contributing factors.

PMID- 17506117
TI  - Leptin in embryos from control and diabetic rats during organogenesis: a
      modulator of nitric oxide production and lipid homeostasis.
AB  - BACKGROUND: Leptin is involved in many metabolic and reproductive events and its
      levels are altered by the diabetic pathology. In this study, leptin
      concentrations and leptin effects on both nitric oxide (NO) and lipid
      concentrations were investigated in embryos from control and diabetic rats.
      METHODS: Diabetes was induced by neonatal streptozotocin administration (90
      mg/kg). Embryos from control and diabetic rats were obtained on days 10.5 and
      13.5 of gestation, corresponding to early organogenesis and post-placentation
      periods respectively. Leptin was analysed by enzyme immunoanalysis and
      immunohistochemistry. Nitrates and nitrites were assessed as an index of NO
      production. Lipid concentrations were analysed by thin layer chromatography.
      RESULTS: Leptin concentrations were decreased in embryos obtained from diabetic
      rats on days 10.5 and 13.5 of gestation when compared to controls. NO
      concentrations, elevated in diabetic embryopathy, were diminished in the presence
      of leptin in the embryos obtained from control and diabetic animals both during
      early organogenesis and after placentation. Leptin additions reduced
      phospholipid, cholesterol and cholesteryl ester concentrations in embryos
      obtained from diabetic rats during early organogenesis, although no leptin
      effects on lipid concentrations were observed in control embryos at this
      developmental stage. In embryos obtained on day 13.5 of gestation leptin
      additions reduced cholesteryl ester concentrations in controls, and diminished
      cholesteryl ester, triglycerides and phospholipids in embryos from diabetic rats.
      CONCLUSIONS: We demonstrated that leptin plays a role in the regulation of NO
      concentrations and lipid homeostasis during embryo organogenesis and that the
      diabetic environment causes a reduction of leptin concentrations in rat embryos.

PMID- 17506118
TI  - C-fos expression at the spinal dorsal horn of streptozotocin-induced diabetic
      rats.
AB  - BACKGROUND: Pain during diabetic neuropathy is associated with peripheral nerve
      damage but recent evidences suggest the occurrence of central effects. We used
      the activation of the c-fos protooncogene to study the activity of spinal dorsal
      horn neurons in streptozotocin (STZ)-induced diabetic rats in the absence of
      stimulation or in response to innocuous or noxious stimuli. METHODS: Four weeks
      after saline or STZ (50 mg/kg) injection, rats were anaesthetized and either not
      further manipulated or submitted to innocuous (gentle touch), noxious mechanical
      (pinching) or noxious thermal (radiant heat) stimulation of the hindlimb skin. In
      each experimental situation, the numbers of Fos-immunoreactive (Fos-IR) neurons
      occurring in the superficial (laminae I-II) or deep (laminae III-V) dorsal horn
      were compared. RESULTS: In the absence of stimulation, STZ-injected rats
      presented significantly higher numbers of Fos-IR neurons than controls, both in
      the superficial and deep dorsal horn (DDH). In comparison with the respective
      baseline levels, innocuous stimulation did not induce a significant increase in
      the numbers of Fos-IR neurons in controls or STZ-rats. Noxious mechanical and
      noxious thermal stimuli increased the numbers of Fos-IR neurons, both in control
      and STZ-rats, but in a more pronounced manner when diabetic rats were subjected
      to noxious mechanical stimulation. CONCLUSIONS: The present study demonstrates
      that the responses of spinal cord neurons are strongly affected during diabetes.
      The higher baseline neuronal activity probably underlies the spontaneous pain
      detected during diabetes since the spinal dorsal horn is the major relay station
      in the ascending transmission of nociceptive input to the brain.

PMID- 17506112
TI  - Identification of bottom-fermenting yeast genes expressed during lager beer
      fermentation.
AB  - It has been proposed that bottom-fermenting yeast strains of Saccharomyces
      pastorianus possess at least two types of genomes. Sequences of genes of one
      genome [S. cerevisiae (Sc)-type] have been found to be highly homologous (more
      than 90% identity) to S. cerevisiae S288C sequences, while those of the other
      [Lager (Lg)-type] are less so. To identify and discriminate Lg-type from Sc-type
      genes expressed during lager beer fermentation, normalized cDNA libraries were
      constructed and analysed. From approximately 22 000 ESTs, 3892 Sc-type and 2695
      Lg-type ORFs were identified. Expression patterns of Sc- and Lg-type genes did
      not correlate with particular cell functions in KEGG classification system.
      Moreover, 405 independent clones were isolated that have no significant homology
      with sequences in the S288C database, suggesting that they include the bottom
      fermenting yeast-specific (BFY) genes. Most of BFY genes have significant
      homology with the S. bayanus genome.

PMID- 17506119
TI  - Chromium picolinate and biotin combination improves glucose metabolism in
      treated, uncontrolled overweight to obese patients with type 2 diabetes.
AB  - BACKGROUND: Chromium and biotin play essential roles in regulating carbohydrate
      metabolism. This randomized, double-blind, placebo-controlled study evaluated the
      efficacy and safety of the combination of chromium picolinate and biotin on
      glycaemic control. METHODS: Four hundred and forty-seven subjects with poorly
      controlled type 2 diabetes (HbA(1c) > or = 7.0%) were enrolled and received
      either chromium picolinate (600 microg Cr(+3)) with biotin (2 mg), or matching
      placebo, for 90 days in combination with stable oral anti-diabetic agents (OADs).
      Major endpoints were reductions in HbA(1c), fasting glucose, and lipids. Safety
      and tolerability were assessed. RESULTS: Change in HbA(1c) was significantly
      different between treatment groups (p = 0.03). HbA(1c) in the chromium
      picolinate/biotin group decreased 0.54%. The decrease in HbA(1c) was most
      pronounced in chromium picolinate/biotin subjects whose baseline HbA(1c) > or =
      10%, and highly significant when compared with placebo (-1.76% vs - 0.68%; p =
      0.005). Fasting glucose levels were reduced in the entire chromium
      picolinate/biotin group versus placebo (-9.8 mg/dL vs 0.7 mg/dL; p = 0.02).
      Reductions in fasting glucose were also most marked in those subjects whose
      baseline HbA(1c) > or = 10.0%, and significant when compared to placebo (-35.8
      mg/dL vs. 16.2 mg/dL; p = 0.01). Treatment was well tolerated with no adverse
      effects dissimilar from placebo. CONCLUSIONS: These results suggest that the
      chromium picolinate/biotin combination, administered as an adjuvant to current
      prescription anti-diabetic medication, can improve glycaemic control in
      overweight to obese individuals with type 2 diabetes; especially those patients
      with poor glycaemic control on oral therapy.

PMID- 17506120
TI  - ACCF/AHA/CDC conference report on emerging infectious diseases and biological
      terrorism threats. Task Force I: direct cardiovascular implications of emerging
      infectious diseases and biological terrorism threats.

PMID- 17506121
TI  - ACCF/AHA/CDC conference report on emerging infectious diseases and biological
      terrorism threats. Task Force II: indirect and secondary cardiovascular effects
      of biological terrorism agents and diseases.

PMID- 17506122
TI  - ACCF/AHA/CDC conference report on emerging infectious diseases and biological
      terrorism threats. Task Force III: prevention and control of cardiovascular
      complications of emerging infectious diseases and potential biological terrorism
      agents and diseases.

PMID- 17506123
TI  - Abstracts of the 84th Annual Meeting of the Physiological Society of Japan, March
      20-22, 2007, Osaka, Japan.

PMID- 17506124
TI  - ACCF/AHA/CDC conference report on emerging infectious diseases and biological
      terrorism threats. Task Force IV: cardiovascular effects of emerging infectious
      diseases and biological terrorism threats: basic, clinical, and population
      science research and training needs.

PMID- 17506125
TI  - Spotlight: Corinna Brunckhorst, MD. Interview by Emma Wilkinson.

PMID- 17506126
TI  - Climbing the cardiology career ladder: Denmark. Interview with Hans Eiskjaer,
      M.D. by Barry Shurlock.

PMID- 17506127
TI  - Comparative study of axial and femoral bone mineral density and parameters of
      mandibular bone quality in patients receiving dental implants.
AB  - INTRODUCTION: In view of the increase in the life expectancy of humans and in
      edentulism of the population above 50 years of age, in which the prevalence of
      osteoporosis is also higher, it is fundamental to better understand the effects
      of systemic bone mass loss on the healing process of dental implants and to
      determine the quality of the bone that surrounds them. The objective of the
      present study was to compare systemic osteoporosis (axial and femoral) and
      parameters of mandibular bone quality, and to evaluate osseointegration in
      postmenopausal women receiving dental implants. METHODS: The sample consisted of
      39 women aged 48-70 years, 19 with a densitometric diagnosis of osteoporosis in
      the lumbar spine and femoral neck and 20 controls with a normal densitometric
      diagnosis. Bone mineral density was measured in the patients and controls by dual
      energy X-ray absorptiometry. Eighty-two osseointegrated dental implants were
      placed in the mandible, 39 of them in the osteoporosis group and 43 in the
      control group. Mandibular bone quality was evaluated by classifying mandibular
      inferior cortical and trabecular bone on panoramic radiographs and by
      histomorphometric analysis of a mandibular bone biopsy. Osseointegration was
      analyzed after 9 months. RESULTS: No significant difference was observed between
      patients with osteoporosis and controls when comparing individuals with a normal
      cortex and those with a severely or moderately eroded cortex determined on
      panoramic radiographs, although patients with MEC/SEC had lower femoral neck BMD
      than those with NC (0.688 +/- 0.17 vs. 0.814+/- 0.144 g/cm2, P<0.012).
      Histomorphometric analysis also revealed no difference in the parameters of bone
      formation or resorption between the two groups. Implant failure was observed in
      only one case. CONCLUSION: We conclude that there is an association between low
      femoral neck BMD and poor mandibular bone quality as assessed by panoramic
      radiography. The loss of one implant (1.2%) is compatible with the literature and
      cannot be attributed to systemic osteoporosis.

PMID- 17506128
TI  - [Better management of atrial fibrillation].

PMID- 17506129
TI  - [Tuberculosis today...just like yesterday].

PMID- 17506130
TI  - Gold Medalist Tribute. Robert F. Mattrey, MD.

PMID- 17506131
TI  - APDR Achievement Award. Janet L. Strife, MD.

PMID- 17506132
TI  - Synthetic folic acid vs. food folates.

PMID- 17506133
TI  - References and standards for infant and childgrowth.

PMID- 17506134
TI  - What's right, what works, who knows?

PMID- 17506135
TI  - Out of box.

PMID- 17506136
TI  - A study evaluating the safety and efficacy of the VelaSmooth system in the
      treatment of cellulite.
AB  - BACKGROUND: Most cellulite treatments are limited in their effectiveness. A
      combination of radiofrequency energy, infrared light and mechanical manipulation
      of the skin and fat merits further examination. OBJECTIVE: Subjects were treated
      with a device combining these energies to evaluate its safety and efficacy.
      METHODS: Sixteen subjects with cellulite were treated twice weekly for 6 weeks
      with the VelaSmooth system. One thigh was treated while the other served as a
      control. Treatment efficacy was measured through circumferential measurements of
      both thighs and by having the investigator and an independent evaluator grade
      visual improvement during follow-up visits. Five patients provided blood
      specimens for assessment of lipid and hormone levels and liver function. Two
      subjects provided three biopsies each in order to monitor the level of estrogen
      and progesterone receptors. RESULTS: The overall thigh circumference decreased in
      71.87% of the treated legs. The mean decrease was 0.44 cm of the lower thigh and
      0.53 cm of the upper thigh. There was significant visual improvement in cellulite
      and skin texture. At the final follow-up visit, 50% of subjects had greater than
      25% improvement (good be very good). CONCLUSION: This study showed positive
      results. Future studies employing higher energy levels and additional treatments
      will likely augment the results of the present study.

PMID- 17506137
TI  - A new modality in the treatment of actinic cheilitis using the Er:YAG laser.
AB  - BACKGROUND: Cheilitis is a precancerous skin lesion most often affecting the
      lower lip. We describe a technique in which this disorder can be treated using
      Er:YAG laser vaporization. The Er:YAG laser wavelength at 2940 nm lies in a very
      strong water absorption peak; tissue interaction results mainly in vaporization
      with minimal heat conduction to adjacent tissue. OBJECTIVE: To evaluate the
      efficacy and outcome of a new modality in the treatment of actinic cheilitis with
      the Er:YAG laser. METHODS: Between 2002 and 2005, 12 patients with actinic
      cheilitis were treated at our institute with the Er:YAG laser. All patients were
      cured with no recurrence to date, and none suffered postoperative complications.
      RESULTS: Patients were men and women aged between 37 and 71 years. The healing
      duration varied from 7 to 30 days (mean 22.33+/-6.91 days) and the follow-up
      ranged from 8 months to 3 years (mean 23.16+/-9.48 months). No recurrences were
      detected in our study. CONCLUSION: Using the Er:YAG laser provides accurate
      tissue ablation, giving a very satisfactory cosmetic result, with a short healing
      period, no lip deformity and no sensation loss.

PMID- 17506139
TI  - Suture material in cosmetic cutaneous surgery.
AB  - Optimal cosmetic surgical results are dependent, in part, on the chosen suture
      material. Given the importance of sutures in wound healing, it is imperative for
      the esthetic physician to choose the correct suture material. There are a wide
      variety of suture materials available and each material presents advantages and
      disadvantages. An ideal suture material has great strength and knot security
      while remaining elastic with minimal tissue reactivity. Given that there is no
      single suture material that is ideal for all situations, the cosmetic physician
      must decide which material is best suited for the particular closure. This review
      will address the major properties of common suture materials and describe their
      advantages and disadvantages.

PMID- 17506138
TI  - Treatment of cutaneous and mucosal telangiectases in hereditary hemorrhagic
      telangiectasia: Report of three cases.
AB  - INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber
      disease is an autosomal dominant disorder characterized by epistaxis,
      mucocutaneous telangiectases and visceral arteriovenous malformations. Cutaneous
      telangiectases are the most obvious sign of this disorder and are not a merely
      cosmetic problem owing to their risk for bleeding, which may constitute an
      authentic matter of concern to these patients. METHODS: Three patients with type
      II HHT disease who presented cutaneous and labial lesions were treated with an
      intense pulsed light (IPL) system associated with a long-pulsed Nd:YAG laser
      (Photoderm-Vasculight, Lumenis). Labial lesions were treated with the IPL system
      and cutaneous lesions were treated with the IPL system and the long-pulsed Nd:YAG
      laser. All treatments were accomplished on an outpatient basis, without
      anesthesia. RESULTS: All three patients experienced a reduction in the frequency
      and severity of bleeding episodes and a great cosmetic improvement, with total
      lesion clearance. Side effects, such as purpura, hypopigmentation,
      hyperpigmentation or textural changes, were not observed. Recurrences were not
      detected after a maximum period of 24 months of follow-up. CONCLUSION: The
      combination of an IPL system and a long-pulsed Nd:YAG laser is efficient and safe
      for the treatment of cutaneous and labial telangiectases in patients with HHT
      disease and constitutes an important tool in improving their quality of life.

PMID- 17506140
TI  - New results for integrase inhibitor.

PMID- 17506141
TI  - Raltegravir demonstrates potency.

PMID- 17506142
TI  - Preclinical data expected for nucleotide GS 9219.

PMID- 17506143
TI  - New lipodystrophy drug.

PMID- 17506144
TI  - [Hyperventilation following head injury: effect on ischaemic burden].

PMID- 17506145
TI  - South Africa unveils new 5-year HIV/AIDS plan.

PMID- 17506146
TI  - Gastroenterology neglected in the UK.

PMID- 17506147
TI  - Drug-resistant gonorrhoeae spread in the USA.

PMID- 17506148
TI  - HIV, injecting drug use and harm reduction: a public health response.
AB  - Injecting drug use is driving HIV epidemics in many countries around the world.
      There is evidence that such epidemics can be averted, halted and reversed if
      comprehensive HIV programmes targeting drug users are put into place. The term
      'harm reduction' is used widely to describe the goals, policies and interventions
      of such programmes. However, despite its rapidly expanding use, the term has no
      universally accepted definition. This paper aims to describe the evolution and
      branding of the term 'harm reduction' and the adoption of the concept across a
      wide range of countries. It highlights a range of issues that remain
      controversial in the harm reduction discourse related to HIV and injecting drug
      use, including: the definition of 'harm reduction' and related terms; the scope
      of harm reduction; the promotion of a public health versus drug control
      dichotomy; the feasibility and appropriateness of harm reduction in low- and
      middle-income countries; and the strength of evidence on harm reduction
      interventions. The paper argues that harm reduction should be a core element of a
      public health response to HIV/AIDS where injecting drug use exists. The
      effectiveness of policies and programmes targeting drug users should be measured
      against public health outcomes. This requires the alignment of drug control
      measures with public health goals. A 'model package' for harm reduction is
      proposed, which provides guidance to countries on the selection of evidence-based
      policies and interventions, including: interventions for reducing HIV
      transmission; treatment of HIV/AIDS and associated comorbidities; appropriate
      models of service delivery; creation of supportive policy, legal and social
      environments; and strengthening of strategic information systems to better guide
      responses.

PMID- 17506149
TI  - Ethnic composition of schools affects episodic heavy drinking only in ethnic
      minority students.
AB  - AIMS: To investigate if school-related contextual factors (school alcohol policy
      and school ethnic composition) explain episodic heavy drinking by individual
      students, while taking individual-level variables into account. DESIGN AND
      PARTICIPANTS: Data were derived from the 2003 Dutch National School Survey on
      Substance Use, a nationally representative cross-sectional study with a total of
      7324 respondents aged 12-16 years. METHODS: Student-level data were collected by
      written questionnaire administered in classroom settings, assessing alcohol and
      drug use as well as socio-demographic and behavioural variables. School-level
      data were gathered by written questionnaire completed by the school principal,
      assessing school policy on substance use and school compositional factors. The
      data were analysed using a multi-level logistic regression model. FINDINGS: The
      study revealed an association between ethnic composition of the school and
      episodic heavy drinking: a relatively high percentage of ethnic minorities (10
      30%) at the school was associated with a lower probability of episodic heavy
      drinking, but only in interaction with individual-level ethnicity. Thus, ethnic
      minority students attending schools of high minority density had less risk of
      episodic heavy drinking (OR = 0.69, 95% CI: 0.47-1.00). None of the school policy
      factors was associated with episodic heavy drinking. CONCLUSIONS: Within a school
      context, peer modelling and reinforcement mechanisms can affect individual
      students' alcohol use, but a certain level of identification with the group and
      the resulting social control may be necessary. School policy seems to have no
      impact on students' alcohol use, possibly because students are faced with these
      only during special events, including school parties and excursions.

PMID- 17506150
TI  - Alcohol drinking pattern and non-fatal myocardial infarction in women.
AB  - AIMS: Evidence continues to emerge indicating the pattern of alcohol consumption
      has important implications for cardiovascular disease (CVD) risk, although the
      majority of studies have focused on men. The aim of the study is to examine the
      association between alcohol volume and various drinking patterns and non-fatal
      myocardial infarction (MI) in women aged 35-69 years. DESIGN AND SETTING:
      Population-based case-control study, 1996-2001. PARTICIPANTS: Incident MI cases
      (n = 320) recruited from Western NY hospitals, controls (n = 1565) identified
      from motor vehicle rolls and Health Care Financing Administration (HCFA) files.
      MEASUREMENTS: Incident MI, volume and drinking patterns for the 12-24 months
      prior to interview (controls) or MI (cases) were assessed in detail. FINDINGS: Of
      cases and controls, 13% were life-time abstainers; current drinkers averaged 2.3
      +/- 2.2 drinks/drinking day. Compared to life-time abstainers, current drinkers
      tended to have a reduced likelihood of MI [odds ratio (OR), 0.67; 95% confidence
      interval (CI), 0.43-1.03]. Volume, drinks/drinking day and frequency were
      associated inversely with MI risk (P trends < 0.001). Wine drinkers (OR, 0.56;
      95% CI, 0.33-0.96) and consumers of mixed beverage types (OR, 0.56, 0.31-1.01)
      had lower odds of MI compared to abstainers. Among current drinkers, for volume
      and most patterns, similar but somewhat weaker associations were noted than when
      abstainers were the reference. In contrast, frequency of intoxication at least
      once/month or more was associated with a strong increased risk compared to
      abstention (OR, 2.90; 95% CI 1.01-8.29) or in current drinkers, never drinking to
      this extent (OR, 6.22; 95% CI 2.07-18.69). CONCLUSION: In this population of
      light to moderate drinkers, alcohol consumption in general was associated with
      decreased MI risk in women; however, episodic intoxication was related to a
      substantial increase in risk.

PMID- 17506151
TI  - From attention-deficit/hyperactivity disorder to medical stimulant use to the
      diversion of prescribed stimulants to non-medical stimulant use: connecting the
      dots.
AB  - AIMS: To describe the connections among the likelihood of attention
      deficit/hyperactivity disorder (ADHD), medical and non-medical methylphenidate
      and amphetamine use and the diversion of prescribed methylphenidate in the
      general adolescent population. DESIGN: Cross-sectional self-reported anonymous
      data from the 2002 Student Drug Use Survey in the Atlantic Provinces. SETTING:
      The Atlantic provinces of Canada. PARTICIPANTS: A total of 12,990 students
      participated. MEASUREMENTS: The outcomes were a positive ADHD screening test,
      medical and non-medical use of methylphenidate, medical and non-medical use of
      amphetamine and the giving and selling of methylphenidate medication by students
      with a prescription. The Ontario Child Health Study Hyperactivity Scale was used
      to screen for ADHD. FINDINGS: The prevalence of a positive ADHD screening test
      was 6% with no significant gender difference. The prevalence of medical and non
      medical methylphenidate use and medical and non-medical amphetamine use was 2.0%,
      6.6%, 1.2% and 8.7%, respectively. A positive ADHD screening test was
      independently predictive of these four patterns of use. About 26% of students
      with prescribed methylphenidate gave or sold some of their medication. Students
      in a class where at least one student had given or sold some of their prescribed
      pills had a 1.52-fold increased risk of non-medical methylphenidate use than
      their counterparts in classes where no giving or selling had taken place.
      CONCLUSIONS: Connections were demonstrated at the population level between ADHD,
      medical methylphenidate use, the diversion of prescribed methylphenidate and the
      non-medical use of methylphenidate. The appropriate assessment and management of
      ADHD are essential to minimize both the risk of diversion and of substance use
      associated with unrecognized or untreated ADHD.

PMID- 17506152
TI  - Persistent pain is associated with substance use after detoxification: a
      prospective cohort analysis.
AB  - AIMS: To test the hypothesis that persistent pain is associated with an increased
      odds of substance use after detoxification. DESIGN: Analysis of data from a
      prospective cohort enrolled in a randomized controlled trial (RCT) to improve
      linkage with primary medical care. SETTING: An urban residential detoxification
      program. PARTICIPANTS: Adults (n = 397) enrolled in the RCT with heroin, alcohol
      or cocaine as a substance of choice and at least one follow-up interview.
      MEASUREMENTS: The key independent variable was pain status: persistent pain
      (moderate to very severe pain at all available interviews), no pain (mild pain or
      less at all available interviews) and intermittent pain (all others). There were
      four outcomes of interest: self-reported use of any substance; heroin/opioid use;
      heavy alcohol use; and cocaine use 24 months after detoxification. Multivariable
      logistic regression controlled for several covariates including demographics,
      physical/sexual abuse, depressive symptoms, duration of follow-up and addiction
      severity at study entry. FINDINGS: Pain in detoxification patients was common;
      16% had persistent pain and 54% had intermittent pain. Persistent pain was
      associated with an increased odds for use of any substance [adjusted odds ratio
      (AOR) 4.2, 95% confidence interval (CI) 1.9-9.3], heroin/opioid use (AOR 5.4, 95%
      CI 2.1-13.8) and heavy alcohol use (AOR 2.2, 95% CI 1.0-4.5) at the 24-month
      follow-up. A statistically non-significant increase in the odds of cocaine use
      (AOR 2.0, 95% CI 0.9-4.6) was also observed. CONCLUSIONS: Among individuals
      leaving residential detoxification, chronic pain is a common problem and is
      associated independently with long-term substance use after detoxification.
      Addressing pain as a treatable chronic condition among adults receiving
      detoxification presents a potential opportunity to improve long-term clinical
      outcomes and warrants further intervention research.

PMID- 17506153
TI  - Does prescribing for opiate addiction change after national guidelines? Methadone
      and buprenorphine prescribing to opiate addicts by general practitioners and
      hospital doctors in England, 1995-2005.
AB  - AIM: To assess changes in opiate prescribing (1995-2005) following a decade of
      national guidelines to address substandard opiate substitution prescribing for
      heroin addiction. DESIGN: A repeat national survey (1995 and 2005) using random
      one-in-four samples of all community pharmacies in England, achieving response
      rates of 75% (1847/2475) in 1995 and 95% (2349/2473) in 2005. Data were obtained
      on 3732 (1995 data) and 9620 (2005 data) prescriptions dispensed in the preceding
      month from the 936 and 1463 pharmacies who were currently dispensing.
      MEASUREMENTS: We have measured impact on practice for seven specific recommended
      changes. FINDINGS: Between 1995 and 2005 the number of substitute opiate
      prescriptions doubled (x 2.03). By 2005, methadone still dominated (down from 97%
      to 83%), buprenorphine increased (from 1% to 16%) and other opiate medications
      virtually disappeared. Changes in the direction of national guidelines included:
      increased daily dose of methadone (from 47.3 mg to 56.3 mg), more frequent
      dispensing (from 38% to 60% as daily installments), more supervised consumption
      (from 0% to 36%) and fewer methadone tablets (from 10.9% to 1.8%). Nevertheless,
      despite the increased mean daily dose, only 41.0% of prescriptions for methadone
      were for daily doses in the recommended 60-120 mg dose range. Only one change was
      not in the direction of the national guidelines--the proportion of prescriptions
      from GPs fell from 41% to 30%, although this still represented an approximate 50%
      increase in the extent of GP prescribing. CONCLUSION: Doubling in provision of
      opiate substitute treatment has occurred, alongside significant improvements in
      the nature of this treatment. These positive changes have occurred in the
      direction of six out of seven of the UK national guidelines.

PMID- 17506154
TI  - Risk factors for methadone outside treatment programs: implications for HIV
      treatment among injection drug users.
AB  - BACKGROUND: Diversion of methadone outside treatment programs occurs, yet reasons
      for use of 'street methadone' are characterized poorly. Self-medication for
      withdrawal symptoms is one plausible hypothesis. Among HIV-infected drug users,
      some antiretroviral medications can reduce potency of methadone, yet any
      association between such effects and the use of supplemental methadone sources
      remains undetermined. OBJECTIVE: To estimate the frequency and risk factors for
      use of street methadone. METHODS: Injection drug users (IDUs) recruited through
      extensive community outreach in 1988-89 and 1994 were followed semi-annually with
      questionnaires about health history, use of licit and illicit drugs including
      methadone and HIV-related assays. Analyses were performed using generalized
      estimating equation logistic regression. RESULTS: Of 2811 IDUs enrolled and
      eligible for analysis, 493 people reported use of street methadone over 12 316
      person-years of follow-up (4.0/100 person-years). In multivariate analyses,
      street methadone use was more common among women, whites, those 40-59 years old,
      those who reported withdrawal symptoms, past methadone program attendance (6-12
      months before visit), recent heroin injection with or without cocaine (but not
      cocaine alone), smoking or sniffing heroin and reported trading sex. Street
      methadone was not associated with HIV infection or treatment. CONCLUSION: The
      results suggest that older IDUs still using heroin may be using street methadone
      to treat signs of withdrawal. The absence of a higher rate of street methadone
      use in HIV seropositive IDUs reveals that antiretroviral/methadone interactions
      are not a primary determinant of use outside of treatment settings.

PMID- 17506155
TI  - The transition from injection to non-injection drug use: long-term outcomes among
      heroin and cocaine users in New York City.
AB  - AIMS: To characterize heroin and cocaine users in New York City who have changed
      from injection to non-injection drug administration and to identify factors
      associated with long-term non-injection use. DESIGN: Two cross-sectional studies
      of heroin and cocaine users in New York City. SETTINGS AND PARTICIPANTS: New
      admissions were recruited at drug abuse treatment programs (2000-04) and
      respondent-driven sampling was used to recruit drug users from the community
      (2004). Both injecting and non-injecting drug users participated in each study.
      'Former injectors' were defined operationally as people who had used heroin
      and/or cocaine in the 6 months prior to the interview and who had injected
      illicit drugs in the past, but whose most recent injection was more than 6 months
      before the study interview. 'Current' injectors were defined as people who had
      injected heroin and/or cocaine in the 6 months prior to the interview.
      MEASUREMENTS: A structured interview on drug use history was administered, and a
      serum sample was collected and tested for the human immunodeficiency virus (HIV).
      FINDINGS: A total of 104 former injectors was recruited for the drug abuse
      treatment program study, and 229 current injectors were recruited for the
      community recruitment study; 160 former injectors and 1731 current injectors were
      recruited from the drug abuse treatment study. Compared with the current
      injectors, former injectors were older and more likely to be African American.
      The former injectors reported long intervals since their most recent injection, a
      mean of 8 years in the drug abuse treatment program study and a mean of 12 years
      in the community recruitment study. The most common reasons for stopping
      injection drug use included concerns about health, social stigmatization and self
      image, and preference for intranasal use as a route of drug administration. The
      results were highly consistent across the two studies. CONCLUSIONS: The
      transition from injection to non-injection use appears to be relatively stable
      behavior change for many former injectors, who report a decade or more without
      injecting. Developing a greater understanding of the transition from injection to
      stable non-injection drug use may provide insights into the natural histories of
      drug use and addiction.

PMID- 17506156
TI  - A randomized, controlled trial to assess the efficacy and safety of a transdermal
      delivery system of nicotine/mecamylamine in cigarette smokers.
AB  - AIMS: To determine the efficacy and safety of nicotine transdermal therapy co
      administered with the nicotine antagonist, mecamylamine, compared to a nicotine
      transdermal patch alone (21 mg nicotine + 6 mg mecamylamine, 21 mg nicotine + 3
      mg mecamylamine, and 21 mg nicotine + 0 mg mecamylamine). DESIGN: Multi-center (n
      = 4), double-blind, randomized, parallel group, repeat-dose study. SETTING:
      Clinical laboratory. PARTICIPANTS: A total of 540 subjects were enrolled into the
      study-135 from each of four sites; 180 patients in each of three treatment arms.
      INTERVENTION: Treatment was administered for the first 6 weeks of the 8-week
      study. Patients were instructed to continue smoking for the first 2 weeks of
      treatment. MEASUREMENTS: The primary efficacy parameter was 4-week continuous
      abstinence after the quit date, confirmed with an expired carbon monoxide of < 10
      parts per million. FINDINGS: Analysis of the 4-week continuous abstinence for the
      intent-to-treat population showed overall rates of 29% (nicotine + 6 mg
      mecamylamine), 29% (nicotine + 3 mg mecamylamine) and 23% (nicotine only) using
      the slip definition which allows smoking in the first 2 weeks after the quit
      date. Statistical analyses revealed no significant treatment differences.
      Analyses using the strict definition (no smoking after the quit date) yielded
      similar non-significant group differences (29%, 27%, 26%). CONCLUSION: If adding
      mecamylamine to nicotine replacement therapy (NRT) improves the chances of
      success at stopping smoking, the results of this study suggest that the effect is
      very small.

PMID- 17506157
TI  - Impact of contractual financial incentives on the ascertainment and management of
      smoking in primary care.
AB  - BACKGROUND: The April 2004 contract for UK general practitioners (GPs) is an
      ambitious attempt to produce substantial changes in clinical practice. We
      investigated the impact of this on delivery of primary care smoking cessation
      interventions. METHODS: We analysed data from patients' medical records that were
      held within a large database called The Health Improvement Network (THIN). We
      calculated for each year between 1990 and 2005 and for each quarter-year from
      2003 the incidence of recording of smoking status in medical records and, in
      smokers, the receipt of GPs' smoking cessation advice and prescriptions for
      nicotine addiction treatments. FINDINGS: Recording of smoking status increased
      temporarily around 1993-4 and then rose gradually from the year 2000. This rise
      was more marked from 2003, with an 88% increase between the first quarters of
      2003 and 2004. The latter quarter was just prior to the introduction of the GP
      contract and higher rates of recording smoking status were sustained for the
      subsequent year. In smokers, there was a broadly similar pattern for the
      proportion recorded as having received brief cessation advice. However, while
      there was a sharp increase in prescriptions for nicotine addiction treatments
      from 2000, no comparable acceleration in this trend from 2003 was apparent.
      INTERPRETATION: The 2004 GP contract increased primary care rates of smoking
      status ascertainment and recording of advice against smoking. The public health
      impact of this contract could be maximized if it also improved GPs' prescribing
      of nicotine addiction treatments.

PMID- 17506158
TI  - Treatment of infertility in the polycystic ovary syndrome.

PMID- 17506159
TI  - Treatment of infertility in the polycystic ovary syndrome.

PMID- 17506160
TI  - GM-CSF autoantibodies in pulmonary alveolar proteinosis.

PMID- 17506161
TI  - Communicating about dying in the ICU.

PMID- 17506162
TI  - Communicating about dying in the ICU.

PMID- 17506163
TI  - The incidentally discovered adrenal mass.

PMID- 17506164
TI  - Urine fluorescence in ethylene glycol poisoning.

PMID- 17506174
TI  - Bioscience in the sun.

PMID- 17506177
TI  - Current world literature. Respiratory infections.

PMID- 17506175
TI  - Postdoc redefined.

PMID- 17506178
TI  - [Chronic recurrent pancreatitis due to aneurysm of splenic artery].

PMID- 17506179
TI  - [Acute cholelithic intestinal obstruction].

PMID- 17506180
TI  - [Clinical case of severe combined trauma].

PMID- 17506181
TI  - [Migration of intrauterine contraceptive into urinary bladder].

PMID- 17506182
TI  - [Informing the patient with cancer of the testis].

PMID- 17506183
TI  - [Videothoracoscopy at the treatment of patient with combined close trauma of
      chest, heart contusion and hemopericardium].

PMID- 17506184
TI  - [Modified endotracheal stent].

PMID- 17506185
TI  - [Glycemic disorders at patients with chronic pancreatitis before and after
      resection of pancreas].

PMID- 17506186
TI  - Fertility in southern Africa: the quiet revolution.

PMID- 17506187
TI  - [Testicular neoplasms in children: lymphatic or metastatic involvement is rare].

PMID- 17506188
TI  - Is solar UV frying fish?

PMID- 17506189
TI  - [Primary mediastinal germ cell tumors].

PMID- 17506191
TI  - Living computers.

PMID- 17506190
TI  - Crossing the scales. Interview by Rebecca Gillan.

PMID- 17506192
TI  - Slavery in the Sudan since 1989.

PMID- 17506193
TI  - Jungles of the mind: the invention of the "tropical rain forest".

PMID- 17506195
TI  - Attaining the full potential of historical archaeology.

PMID- 17506194
TI  - Historical archaeology adrift?

PMID- 17506196
TI  - New sources, new theses, and new organizations in the new Germany: recent
      research on the history of German agriculture.

PMID- 17506197
TI  - The ministry and the malady.

PMID- 17506198
TI  - El negro, el nino, witchcraft and the absence of rain in Botswana.

PMID- 17506199
TI  - [Program for detection of patients with ineffective therapy with beta
      adrenoblockers and comparative assessment of efficacy of addition of
      trimetazidine MB or isosorbide dinitrate in stable angina. Results of a Russian
      Study Parrallel].

PMID- 17506200
TI  - [Special features of hypertension in patients with postinfarction cardiosclerosis
      consuming increased amounts of salt].

PMID- 17506201
TI  - [Arteriovenous malformation of the posterior auricular artery in the middle ear].

PMID- 17506202
TI  - [Recovery of hearing in a patient with a baroacoustic trauma].

PMID- 17506203
TI  - [Facial nerve paresis in patients with infectious mononucleosis and otitis
      media].

PMID- 17506204
TI  - [Treatment of oropharyngeal cancer with metastases to cervical lymph nodes].

PMID- 17506205
TI  - [Three cases of rhinolith].

PMID- 17506206
TI  - [Management of the rooms of medico-genetic consulting].

PMID- 17506207
TI  - [Otorhinolaryngological aspects of mucoviscidosis].

PMID- 17506208
TI  - [Neuroendocrine tumors of the larynx].

PMID- 17506209
TI  - More on: "Doctors Must Be Healers".

PMID- 17506210
TI  - Doctors as pawns? Law and medical ethics at Guantanamo Bay.

PMID- 17506211
TI  - The number of live animals used in experiments after breeding in research
      facilities in 2004: results of survey.

PMID- 17506212
TI  - First, do no harm: health professionals and Guantanamo.

PMID- 17506213
TI  - [Combined antihypertensive therapy: are all combinations equally beneficial?].

PMID- 17506214
TI  - [Classification of germ cell tumors of the testis].

PMID- 17506215
TI  - H&HN--eight decades of health care: 80th anniversary. The 1950s.

PMID- 17506216
TI  - H&HN--eight decades of health care: 80th anniversary. Efficiency, speed and
      patient safety drive fast-paced evolution of medical equipment.

PMID- 17506217
TI  - Practical ethics. Can you avoid a quid pro quo?

PMID- 17506218
TI  - The neuroanatomy of an amphibian embryo spinal cord.
AB  - Horseradish peroxidase has been used to stain spinal cord neurons in late embryos
      of the clawed toad (Xenopus laevis). It has shown clearly the soma, dendrites and
      axonal projections of spinal sensory, motor and interneurons. On the basis of
      light microscopy we describe nine differentiated spinal cord neuron classes.
      These include the Rohon-Beard cells and extramedullary cells which are both
      primary sensory neurons, one class of motoneurons that innervate the segmental
      myotomes, two classes of interneurons with decussating axons, three classes of
      interneurons with ipsilateral axons and a previously undescribed class of
      ciliated ependymal cells with axons projecting ipsilaterally to the brain. We
      believe that all differentiated neuron classes are described and that this
      anatomical account is the most complete for any vertebrate spinal cord.

PMID- 17506219
TI  - Intracellular recordings from spinal neurons during 'swimming' in paralysed
      amphibian embryos.
AB  - Intracellular microelectrode recordings have been made from probable motoneurons
      in the spinal cord of Xenopus laevis embryos during fictive 'swimming' in
      preparations paralysed with the neuromuscular blocking agent tubocurarine. These
      cells had resting potentials of -50 mV or more. During spontaneous or stimulus
      evoked 'swimming' episodes: (a) the cells were tonically excited; the level of
      tonic synaptic excitation and the conductance increase underlying it were both
      inversely related to the 'swimming' cycle period; (b) the cells usually fired one
      spike per cycle in phase with the motor root burst on the same side; spikes did
      not overshoot zero and were evoked by phasic excitatory synaptic input on each
      cycle, superimposed on the tonic excitation; (c) in phase with motor root
      discharge on the opposite side of the body, the cells were hyperpolarized by a
      chloride-dependent inhibitory postsynaptic potential. The nature of synaptic
      potentials during 'swimming' was evaluated by means of intracellular current
      injections. The 'swimming' activity could be controlled by natural stimuli. The
      results provide clear evidence on the relation of tonic excitation to rhythmic
      locomotory pattern generation, and indirect evidence for reciprocal inhibitory
      coupling between antagonistic motor systems.

PMID- 17506220
TI  - Experiments on the central pattern generator for swimming in amphibian embryos.
AB  - The central nervous system of paralysed Xenopus laevis embryos can generate a
      motor output pattern suitable for swimming locomotion. By recording motor root
      activity in paralysed embryos with transected nervous systems we have shown that:
      (a) the spinal cord is capable of swimming pattern generation; (b) swimming
      pattern generator capability in the hindbrain and spinal cord is distributed; (c)
      caudal hindbrain is necessary for sustained swimming output after discrete
      stimulation. By recording similarly from embryos whose central nervous system was
      divided longitudinally into left and right sides, we have shown that: (a) each
      side can generate rhythmic motor output with cycle periods like those in
      swimming; (b) during this activity cycle period increases within an episode, and
      there is the usual rostrocaudal delay found in swimming; (c) this activity is
      influenced by sensory stimuli in the same way as swimming activity; (d) normal
      phase coupling of the left and right sides can be established by the ventral
      commissure in the spinal cord. We conclude that interactions between the
      antagonistic (left and right) motor systems are not necessary for swimming rhythm
      generation and present a model for swimming pattern generation where autonomous
      rhythm generators on each side of the nervous system drive the motoneurons.
      Alternation is achieved by reciprocal inhibition, and activity is initiated and
      maintained by tonic excitation from the hindbrain.

PMID- 17506221
TI  - Hospitals make progress on quality, safety goals, but can do better, Joint
      Commission says.

PMID- 17506222
TI  - Depression and cardiovascular comorbidity.
AB  - Depression has long had a popular link to cardiovascular disease and death.
      However, only during the last 15 years has scientific evidence supporting this
      common wisdom been available. Beginning in the early 1990s, there began to
      accumulate community-based epidemiological evidence that medically healthy,
      depressed patients followed for long periods of time were at increased risk of
      both cardiovascular disease and cardiac death. In the mid-1990s, evidence
      appeared to indicate that depression following a heart attack increased the risk
      of death. It is now apparent that depression aggravates the course of multiple
      cardiovascular conditions. There are two major unanswered questions. One is
      whether treating depression will reduce the risk of cardiovascular disease and
      death. Here, preliminary, but not definitive, evidence suggests that the
      serotonin reuptake inhibitors may be useful. The other unanswered question
      regards the mechanisms that underlie this link between depression and
      cardiovascular disease. There is strong evidence linking platelet activation,
      autonomic activity and inflammatory markers to both depression and heart disease,
      but why these links exist is far less clear.

PMID- 17506223
TI  - Common genetic factors for depression and cardiovascular disease.
AB  - There is increasing knowledge regarding the considerable comorbidity between
      depression and cardiovascular disease, which are two of the most common disorders
      in developed countries. The associated vulnerability is not unidirectional, as
      the presence of cardiovascular disease can also influence mood states. Although
      this may be the result of psychological factors, common biological mechanisms,
      including genetic ones, are thought to be responsible for this interaction; we
      can thus question whether variations in genes could be predisposing factors.
      Regarding the multiple interactions in the mechanisms between depression and
      cardiovascular system disorders, e.g., dysfunctions in the hypothalamic-pituitary
      adrenocortical and sympathoadrenal axis and the response to stress, the
      importance of the serotonergic and immune systems, or the impact on the renin
      angiotensin system, several candidate genes are being investigated. However,
      despite the interest in unraveling the potential susceptibility genes for both
      disorders, most available studies have so far dealt with the impact of
      polymorphisms in relation to either depression or cardiovascular disease. A few
      recent studies have now examined the effects of gene-gene or gene-environment
      interactions, and are investigating the impact of "depression-related" variants
      on cardiac response to stress. The first promising results were obtained with the
      serotonin transporter, and it may be hypothesized that this polymorphism
      interacts via the impact of the S allele on depression and via the effect of the
      L allele on platelet activation. However, the role played by various other
      candidate genes remains to be determined, especially regarding the question as to
      whether they are indicative of common pathophysiological mechanisms, or for
      identifying a subgroup of patients with somatic disorders that are more closely
      related to psychiatric symptoms.

PMID- 17506224
TI  - Neuropsychiatric consequences of cardiovascular medications.
AB  - The use of cardiovascular medications can have a variety of neuropsychiatric
      consequences. Many cardiovascular agents cause higher rates of fatigue and
      sedation than placebo, and case reports of medication-induced mood syndromes,
      psychosis, and cognitive disturbances exist for many cardiovascular drugs.
      Depression has been associated with P3-blockers, methyldopa, and reserpine, but
      more recent syntheses of the data have suggested that these associations are much
      weaker than originally believed. Though low cholesterol levels have been
      associated with depression and suicide, lipid-lowering agents have not been
      associated with these adverse effects. Finally, cardiovascular medications may
      have beneficial neuropsychiatric consequences; for example, the use of clonidine
      in patients with attention deficit-hyperactivity disorder, the use of prazosin
      for patients with post-traumatic stress disorder; and the use of propranolol for
      performance anxiety and akathisia.

PMID- 17506225
TI  - Influence of antidepressants on hemostasis.
AB  - Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs),
      are widely used for the treatment of depression and anxious disorders. The
      observation that depression is an independent risk factor for cardiovascular
      mortality and morbidity in patients with ischemic heart disease, the assessment
      of the central role of serotonin in pathophysiological mechanisms of depression,
      and reports of cases of abnormal bleeding associated with antidepressant therapy
      have led to investigations of the influence of antidepressants on hemostasis
      markers. In this review, we summarize data regarding modifications of these
      markers, drawn from clinical studies and case reports. We observed an association
      between the type of antidepressant drug and the number of abnormal bleeding case
      reports, with or without modifications of hemostasis markers. Drugs with the
      highest degree of serotonin reuptake inhibition--fluoxetine, paroxetine, and
      sertraline--are more frequently associated with abnormal bleeding and
      modifications of hemostasis markers. The most frequent hemostatic abnormalities
      are decreased platelet aggregability and activity, and prolongation of bleeding
      time. Patients with a history of coagulation disorders, especially suspected or
      documented thrombocytopenia or platelet disorder, should be monitored in case of
      prescription of any serotonin reuptake inhibitor (SRI). Platelet dysfunction,
      coagulation disorder, and von Willebrand disease should be sought in any case of
      abnormal bleeding occurring during treatment with an SRI. Also, a non-SSRI
      antidepressant should be favored over an SSRI or an SRI in such a context.
      Considering the difficulty in performing platelet aggregation tests, which are
      the most sensitive in SRI-associated bleeding, and the low sensitivity of
      hemostasis tests when performed in case of uncomplicated bleeding in the general
      population, establishing guidelines for the assessment of SRI-associated bleeding
      complications remains a challenge.

PMID- 17506226
TI  - Hypertension, cognitive decline, and dementia: an epidemiological perspective.
AB  - Hypertension is a known risk factor for stroke, and thus for vascular dementia.
      However, recent large observational studies have suggested that high blood
      pressure may also play a role in Alzheimer's disease. The mechanisms linking
      hypertension to Alzheimer's disease remain to be elucidated, but white matter
      lesions seen on cerebral magnetic resonance imaging appear to be a good marker of
      this association. It is not yet clearly established whether lowering blood
      pressure reduces the risk of white matter lesions and dementia, so large trials
      dealing with this question are eagerly awaited. These future trials could confirm
      the hope that, by lowering blood pressure, we may have a preventive treatment for
      dementia. This issue is of major importance, as the number of cases of dementia
      is expected to rise

PMID- 17506227
TI  - Gender differences in cardiovascular disease and comorbid depression.
AB  - Although gender is increasingly perceived as a key determinant in health and
      illness, systematic gender studies in medicine are still lacking. For a long
      time, cardiovascular disease (CVD) has been seen as a "male" disease, due to
      men's higher absolute risk compared with women, but the relative risk in women of
      CVD morbidity and mortality is actually higher. Current knowledge points to
      important gender differences in age of onset, symptom presentation, management,
      and outcome, as well as traditional and psychosocial risk factors. Compared with
      men, CVD risk in women is increased to a greater extent by some traditional
      factors (e.g., diabetes, hypertension, hypercholesterolemia, obesity), and
      socioeconomic and psychosocial factors also seem to have a higher impact on CVD
      in women. With respect to differences in CVD management, a gender bias in favor
      of men has to be taken into account, in spite of greater age and higher
      comorbidity in women, possibly contributing to a poorer outcome. Depression has
      been shown to be an independent risk factor and consequence of CVD; however,
      concerning gender differences, the results have been inconsistent. Current
      evidence suggests that depression causes a greater increase in CVD incidence in
      women, and that female CVD patients experience higher levels of depression than
      men. Gender aspects should be more intensively considered, both in further
      research on gender differences in comorbid depression, and in cardiac treatment
      and rehabilitation, with the goal of making secondary prevention more effective.

PMID- 17506228
TI  - Neuropsychiatric consequences of coronary artery bypass grafting and
      noncardiovascular surgery.
AB  - This paper reviews findings regarding short- and long-term neuropsychiatric
      consequences of coronary artery bypass grafting (CABG) and noncardiac surgery.
      Stroke is one of the potentially most serious complications of CABG; studies have
      identified some demographic and medical risk factors. Short-term
      neuropsychological deficits are common after CABG, but have been similarly
      documented in noncardiac surgery patients, and may therefore not be specific to
      this procedure. Neuropsychological deficits in some cognitive areas may persist
      over time. Patients with depression before surgery are likely to have persistent
      depression afterwards. Also, depression does not account for the cognitive
      decline after CABG. Conflicting findings, and the possible methodological
      limitations of current published studies, are presented and discussed.

PMID- 17506229
TI  - Association study of T102C 5-HT(2A) polymorphism in schizophrenic patients:
      diagnosis, psychopathology, and suicidal behavior.
AB  - The objective of this study was to examine the association between the serotonin
      (5-HT)2A gene polymorphism (102T/C) and suicidal behavior in schizophrenic
      inpatients. We studied 129 subjects who met the diagnostic criteria for
      schizophrenia according to a structured clinical interview (MINI-PLUS). Patients
      underwent a semistructured interview to assess suicide attempt history and its
      characteristics. In addition, at least one close relative of the patient was
      interviewed to assess proband and family suicidal behavior. Healthy controls were
      students and hospital staff members free of psychiatric and medical illness.
      Genotypes were determined after polymerase chain reaction amplification of the
      region of 5-HT(2A)/T102C containing the polymorphic site and digestion with the
      restriction enzyme Hpall. We found no association between suicidal attempt
      history and suicide attempt characteristics and genotypic or allele frequencies.
      Suicidal behavior was also not associated with demographic or psychopathological
      characteristics. These results suggest that the 5-HT(2A) gene polymorphism
      (102T/C) is not involved in genetic susceptibility to suicidal behavior, but
      further studies in a larger sample are needed.

PMID- 17506230
TI  - Evaluation of outcomes in SPA-treated osteoarthrosic patients.
AB  - INTRODUCTION: Osteoarthrosis is the most prevalent joints disorder and it is also
      the most frequent cause of physical disability in the elderly. When surgery is
      not indicated, symptomatic drugs are generally used. These treatments are
      frequently associated to balneotherapy. In fact, balneotherapy or spa therapy has
      been widely used in classical medicine as a cure for such diseases. The aim and
      significance of this study is to evaluate the impact of thermalism in subjects
      suffering from osteoarthrosis. METHODS: We randomly selected 220 osteoarthrosic
      subjects (STs = spa treatment subjects), aged from 40 to 90, that usually
      undergone mud pack therapy and balneotherapy at least once a year. They were
      enrolled in thermal establishments in the Euganean Basin. We also recruited, as
      control group, 172 osteoarthrosic subjects (NCs = normal care subjects) that
      never underwent any spa therapy. A questionnaire, comprehensive of a disability
      score, was administered by physicians to each subject. RESULTS: STs reported to
      suffer from osteoarthrosis for more years than NCs. Furthermore STs significantly
      suffered more than NCs from pain in several joints, and they also showed a more
      elevated average number of painful joints. In spite of that, STs used less drugs
      than NCs, and showed a higher degree of disability due to osteoarthrosis (p <
      0.001). CONCLUSION: The regular use of mudpack and balneotherapy seem to improve
      the wellness, and the spa treatment seems to help the achievement of this goal.
      In this regard it might be important to encourage new investigations in order to
      assess in which measure thermal therapy contribute to the wellness improvement.

PMID- 17506231
TI  - Epidemiology and burden of rotavirus-associated hospitalizations in Ferrara,
      Italy.
AB  - Objective of this study was to provide data on hospitalizations for rotavirus
      gastroenteritis (RVGE) in Ferrara, Italy. The study was conducted analyzing the
      hospital discharge forms of all children admitted to the Pediatric Department of
      the University of Ferrara, Arcispedale Sant'Anna, from January 2001 through
      December 2005. The database was searched for all gastrointestinal diseases and in
      particular RVGE. During the period under study 3277 children, of which 2038 <60
      months of age, were hospitalized; 247 children < 5 years old were admitted for
      acute gastroenteritis and 89 (4.4% of all and 36% of gastroenteritis-related
      hospitalizations) had rapid screening tests positive for rotavirus. A seasonal
      pattern was observed for RVGE with an increase in winter and early spring. The
      average length of hospital stay was 5.7 days. The median cost of each
      hospitalized case of RVGE ranged between 1417 and 1595 Euros. The present
      research confirms that rotavirus gastroenteritis represents an important cause of
      hospitalization in children and is responsible for significant costs for the
      Public Health Care System. An effective vaccination program could significantly
      reduce the incidence of hospitalization and the associated costs.

PMID- 17506232
TI  - Evaluation of toxic chemical parameters and ecotoxicity levels in bottled mineral
      waters.
AB  - Heavy metals, phthalates, characterizing elements, CO2 concentrations and pH and
      hardness levels were measured in forty samples of bottled mineral waters. In some
      samples arsenic, manganese, mercury and selenium were present in higher
      concentrations than permitted by Italian law. No significant release of
      phthalates from containers in PET was observed. In the same samples, toxicity
      tests with Daphnia magna were carried out. Toxicity levels, expressed as % of
      immobile organisms, ranged from 0 to 100%; generally the highest toxicity values
      were found in the hardwaters.

PMID- 17506233
TI  - Quality in emergency departments: a study on 3,285,440 admissions.
AB  - INTRODUCTION: A multi-centre study has been conducted, during 2005, by means of a
      questionnaire posted on the Italian Society of Emergency Medicine (SIMEU) web
      page. Our intention was to carry out an organisational and functional analysis of
      Italian Emergency Departments (ED) in order to pick out some macro-indicators of
      the activities performed. Participation was good, in that 69 ED (3,285,440
      admissions to emergency services) responded to the questionnaire. METHODS: The
      study was based on 18 questions: 3 regarding the personnel of the ED, 2 regarding
      organisational and functional aspects, 5 on the activity of the ED, 7 on triage
      and 1 on the assessment of the quality perceived by the users of the ED. RESULTS
      AND CONCLUSION: The replies revealed that 91.30% of the ED were equipped with
      data-processing software, which, in 96.83% of cases, tracked the entire itinerary
      of the patient. About 48,000 patients/year used the ED: 76.72% were discharged
      and 18.31% were hospitalised. Observation Units were active in 81.16% of the ED
      examined. Triage programmes were in place in 92.75% of ED: in 75.81% of these,
      triage was performed throughout the entire itinerary of the patient; in 16.13% it
      was performed only symptom-based, and in 8.06% only on-call. Of the patients
      arriving at the ED, 24.19% were assigned a non-urgent triage code, 60.01% a
      urgent code, 14.30% a emergent code and 1.49% a life-threatening code. Waiting
      times were: 52.39 min for non-urgent patients, 40.26 min for urgent, 12.08 for
      emergent, and 1.19 for life-threatening patients.

PMID- 17506234
TI  - Foreign bodies in the upper airways: the experience of two Italian hospitals.
AB  - OBJECTIVE: To study the pattern of foreign bodies in the upper airways as
      emerging from the hospital records in the Bologna and Siena hospitals in Italy
      1997-2002. METHODS: A retrospective review of hospital records was performed
      using a standardized protocol. All injuries with ICD9 (International
      Classification of Diseases, 9'h revision) codes ranging from 931 to 934 which
      occurred in children age 0-14 were considered for the database. RESULTS: One
      hundred ninety seven patients were included in the database with a diagnosis of
      Foreign Bodies (FB) over the study period, 78 with ICD931, 105 with ICD932, 12
      with ICD933 and 2 with ICD934 discharge diagnosis. Of the 197 patients, 51.90% of
      the patients were males and the 48.10% were female. Median age was 4 (2, 6). At
      the moment of the injury, the child was eating (11%), playing (83%) or studying
      (4%) or cleaning ears (2%). The child was supervised by an adult in doing his/her
      activities at the moment of injury in the 84.2% of the cases. The child reached
      the hospital using always private transport (100%), never by using an emergency
      transport (0%). Most commonly, FB were extracted in ambulatory (95.4%), more
      rarely using an endoscopic procedure (4.1%), and never using surgery.
      Hospitalization was required in the 0.5% of cases (1). CONCLUSIONS: Our study
      showed the substantial epidemiological similarity of the Italian data with the
      experience of other center in the world. The burden of chocking was very limited
      in our country, as proven by the limited access to emergency and more invasive
      procedures. Nevertheless, some consideration can be made from the preventive
      point of view. Quite surprisingly, the majority of injuries occurred under the
      supervision of an adult in playing or recreational activities.

PMID- 17506235
TI  - Epidemiology and direct medical costs of human leishmaniasis in Italy.
AB  - INTRODUCTION: In the last decades, visceral Leishmaniasis infection rate has
      increased in Western Mediterranean areas. Epidemiological data show that in
      Italy, especially in some regions, the prevalence of canine form is high. The aim
      of this study is to evaluate the epidemiological setting of Leishmaniasis in
      Italy, according to age groups and geographical areas, and to estimate the
      associated direct medical costs. METHODS: The study examined the ordinary and day
      hospital discharges and the respective mean of hospital length of stay for
      Leishmaniasis and visceral Leishmaniasis in Italy, during the period 1999-2003.
      Moreover, we collected data about notifications of Leishmaniasis, from 1993 to
      2004, and mortality due to this infectious disease, from 1993 to 1998. We
      evaluated the prevalence rates of discharges, the visceral and cutaneous
      Leishmaniasis notifications incidence rates and the mortality rates from disease,
      per 1,000,000 residents. Costs analysis was performed getting DRG number 423
      rate, which corresponds to "other diagnosis related to infectious and parasitary
      diseases". RESULTS: Ordinary discharges decreased in the study period, while day
      hospital discharges increased. Sicilia, Campania and Lazio regions showed the
      highest number of ordinary hospital discharges for Leishmaniasis (prevalence
      rates were respectively 16.29, 15.02 and 12.83 per 1,000,000 residents, in 2003).
      Campania and Sicilia showed also the highest prevalence rates of day-hospital
      discharges (respectively 17.29 and 35.39 per 1,000,000 residents in 2003). The
      analysis of incidence rates of notifications showed a cyclic trend of the
      visceral form of the disease, with the highest rates observed in the group aged 0
      14 years (incidence rates per 1,000,000: 7.46 in 1996 and 8.59 in 2000). The
      highest mortality rates were observed in the group aged over 65 years; low but
      constant mortality rates for Leishmaniasis were seen in the age group 25-64
      years. Direct costs for both ordinary and day-hospital admissions were:
      1,561,218.46 Euro in 1999; 1,637,256.44 Euro in 2000; 1,459,892.92 Euro in 2001,
      1,468,983.58 Euro in 2002 and 1,370,227.80 Euro in 2003. DISCUSSION: Discharges
      for Leishmaniasis showed non-homogeneous trend in Italy, especially in coastal
      Regions. Leishmaniasis notifications have slowly increased after 1993 and a high
      number of notifications was observed in the 0-14 years old group. The highest
      mortality rates were reported in the extreme age-groups: mortality was relevant
      for patients over 65 years. Moreover, cost analysis showed that health care of
      human Leishmaniasis requires long time of hospitalization with consequent high
      costs. Conclusion. Preventive measures have to be turned to extreme age groups.
      For future studies issues such as high costs of treating disease, cost
      effectiveness evaluation of the 'current therapeutic approach compared to
      preventive interventions on dogs and vector insects would be of interest.

PMID- 17506236
TI  - Old drug, new data, continued vigilance.

PMID- 17506237
TI  - Parkinson disease: managing a complex, progressive disease at all stages.
AB  - Parkinson disease is a complex neurodegenerative disease with both motor and
      nonmotor symptoms. Levodopa remains the mainstay of therapy but is associated
      with motor complications as the disease progresses. A levodopa-sparing strategy
      may reduce or delay the onset of motor complications. New medical and surgical
      therapies offer improved control of motor complications in advancing disease.
      Recognition and treatment of nonmotor symptoms can improve quality of life
      throughout the course of the disease.

PMID- 17506238
TI  - In vitro fertilization update.
AB  - Success rates with in vitro fertilization (IVF) continue to improve as we gain
      insight into optimal culture conditions for gametes and embryos. New procedures
      such as in vitro egg maturation, preimplantation genetic testing, single embryo
      transfer, and oocyte freezing hold the promise of reducing the cost,
      inconvenience, and risks of IVF, as well as preserving future fertility. We
      provide an overview of the current and experimental assisted reproductive
      technology techniques.

PMID- 17506239
TI  - Anabolic steroid abuse: psychiatric and physical costs.
AB  - The psychiatric effects of anabolic-androgenic steroids (i.e., testosterone and
      its derivatives) have been less well studied than their physical effects but are
      reported to include depression, mania, psychosis, and aggression. Dependence can
      also occur, with withdrawal involving psychiatric and physical symptoms. Adverse
      effects of steroid abuse should be managed by discontinuing the drugs-by tapering
      if necessary-and by treating the symptoms.

PMID- 17506240
TI  - Viral infections and the kidney: HIV, hepatitis B, and hepatitis C.
AB  - Infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or
      hepatitis C virus (HCV) can cause rapidly progressive renal disease, so prompt
      recognition and management are critical. Viral glomerulonephropathy can now often
      be successfully managed with a specific combination of antiviral therapy,
      immunosuppressants, plasmapheresis, angiotensin-converting enzyme (ACE)
      inhibitors, and angiotensin 2 receptor blockers.

PMID- 17506241
TI  - Intravenous iodinated contrast agents: risks and problematic situations.
AB  - Many of today's diagnostic imaging studies use intravenous contrast media to
      adequately evaluate disease processes. Although these agents are generally safe,
      their use poses some risks and, in some situations, is problematic. The risks
      include contrast-induced nephropathy.

PMID- 17506242
TI  - Newer hormonal therapies: lower doses; oral, transdermal, and vaginal
      formulations.
AB  - Hormonal therapy remains the gold standard for treating menopausal symptoms. In
      addition, some formulations are indicated for preventing and treating bone loss.
      In this article, we review some of the hormonal regimens that have been approved
      in the past 5 years.

PMID- 17506243
TI  - Neurologic effects of hyponatremia and its treatment.

PMID- 17506244
TI  - Should all patients with acute pericarditis be treated with colchicine?

PMID- 17506245
TI  - Management of peritoneal surface malignancy: a short history.

PMID- 17506246
TI  - The natural history of free cancer cells in the peritoneal cavity.

PMID- 17506247
TI  - Pathological evaluation and implications of serosal involvement in
      gastrointestinal cancer.

PMID- 17506248
TI  - Principles of perioperative intraperitoneal chemotherapy for peritoneal
      carcinomatosis.

PMID- 17506249
TI  - Experimental and pharmacokinetic studies in intraperitoneal chemotherapy: from
      laboratory bench to bedside.

PMID- 17506250
TI  - Technology for the delivery of hyperthermic intraoperative intraperitoneal
      chemotherapy: a survey of techniques.
AB  - Peritoneal metastases are common sequelae of gastrointestinal malignancy. The
      treatment of peritoneal metastases through use of aggressive surgical
      cytoreduction including peritonectomy coupled with HIPEC has now been reported in
      several large single-institution series. The available literature suggests that
      in experienced hands and with appropriate patient selection cytoreduction and
      HIPEC can be an effective therapy, particularly when all macroscopic tumor
      deposits are removed. Different techniques involving the administration of
      intraperitoneal chemotherapy have been reported, including the closed
      intraoperative technique, the open or coliseum technique, and the open technique
      using a PCE device. All techniques have been associated with mortality and
      morbidity that is significant, but generally consistent with other major surgical
      procedures. In theory, the coliseum and PCE techniques may have less associated
      morbidity because of improved heat distribution; however, this remains to be
      definitively proven in a controlled clinical trial. Such controlled studies are
      critical to defining the best techniques for HIPEC administration and the
      appropriate role for this treatment regimen in patients with peritoneal
      metastases. The development of a program in cytoreductive surgery and HIPEC
      requires a comprehensive patient care team led by appropriately trained surgeons.
      Such teams are best suited to provide the highest-quality care to patients with
      peritoneal surface malignancy.

PMID- 17506251
TI  - Adjuvant intraperitoneal chemotherapy: a review.

PMID- 17506252
TI  - Clinical research methodology in peritoneal surface oncology: a difficult
      challenge.

PMID- 17506253
TI  - Lessons learnt from clinical trials in peritoneal surface oncology: colorectal
      carcinomatosis.

PMID- 17506254
TI  - Experimental models and questions in basic science research for pseudomyxoma
      peritonei.

PMID- 17506255
TI  - Peritoneal carcinomatosis of colorectal origin: recent advances and future
      evolution toward a curative treatment.

PMID- 17506256
TI  - Pathologic characterization and differential diagnosis of malignant peritoneal
      mesothelioma.

PMID- 17506257
TI  - Advances in clinical research and management of diffuse peritoneal mesothelioma.

PMID- 17506258
TI  - Advances in the management of gastric cancer with peritoneal dissemination.

PMID- 17506259
TI  - Intraperitoneal chemotherapy in the management of ovarian cancer.

PMID- 17506260
TI  - How to help a battered woman.

PMID- 17506261
TI  - The power of positive nursing.

PMID- 17506262
TI  - [Organization and development of medical specialities in developing countries].

PMID- 17506263
TI  - [Management of HIV/AIDS patients in Kompong Cham, Cambodia].
AB  - In 2003 the NGO Medecins sans Frontieres started an anti-viral drug treatment
      program for HIV/AIDS patients in the regional hospital of Kompong Cham, Cambodia.
      In 2005 a total of 1100 adults and 149 children were on the active list. Sixty
      percent of new patients were at WHO stages 3 or 4. Compliance with HAART was high
      after 24 months. Access to second-line regimens is discussed.

PMID- 17506264
TI  - [Venomous and poisonous animals. III. Elapidae snake envenomation].
AB  - Envenomation by Elapidae snakes is less frequent than by Viperidae snakes but
      represents a true medical emergency due to rapid progression of cobra syndrome.
      Elapidae venom contains neurotoxins that paralyze striated muscles especially in
      the thoracic cavity. Respiratory paralysis can occur within a few hours and is
      preceded by neurological symptoms (local paresthesia and paresis progressing to
      the cranial nerves). When cobra envenomation is suspected, antivenom
      administration by the direct venous route must be undertaken as quickly as
      possible to stop the envenomation process. Artificial ventilation is necessary in
      case of dyspnea.

PMID- 17506265
TI  - [Human Bocavirus: a new respiratory pathogen?].

PMID- 17506266
TI  - [The 20th annual meeting of the Association of French Speaking Pediatricians].

PMID- 17506267
TI  - [Greenhouse effect and climate warming: what impact do these have on vector-borne
      infectious disease?].

PMID- 17506268
TI  - [Cutaneous sporotricosis in a Malagasy patient].

PMID- 17506269
TI  - [Madagascar: public health situation on the "Big Island" at the beginning of the
      21st century].
AB  - The main public health issue in Madagascar at the beginning of the 21st century
      still involves transmissible infectious diseases including re-emerging diseases
      such as bubonic plague and emerging diseases such as HIV/AIDS, dengue fever and
      Chikungunya virus infection. Health and hygiene especially access to clean water
      is still poor especially in rural areas. No improvement in the public health
      situation with regard to malaria, schistomosomiais or cysticercosis as well as
      non-infectious diseases such as protein-energy malnutrition is expected within
      the next decade.

PMID- 17506270
TI  - [African programme for onchocerciasis control (APOC): entomological aspects of
      Onchocerca volvulus transmission by Simulium neavei in the Basin of Sankuru
      (Eastern Kasai, Democratic Republic of Congo)].
AB  - As part of a study to evaluate the long-term impact of community-directed
      treatment with ivermectin (CDTI), baseline entomological data on the transmission
      of onchocerciasis in the forest zone of the Eastern Kasai Province were collected
      from July 1998 to January 1999. Species of the Simulium neavei complex were the
      only vectors found in the site during the study. Nuisance activity was low with a
      mean biting rate of only 32.5 bites/man/day. The mean parturity rate was 29.4%,
      the mean rate of infected females was 14.5% and the mean number of infective
      Onchocerca larvae per 1000 parous flies was 659. These findings clearly show that
      the S. neavei population at the study site has high vector capability and
      constitutes a large microfilarial reservoir. The entomological features found in
      the study area are consistent with a hyper-endemic zone.

PMID- 17506271
TI  - [Annual assessement of a mobile ultrasonography service in the region of
      Ziguinchor, Senegal].
AB  - To provide rural populations with access to ultrasound scanning, a mobile
      ultrasound service was set up in the health districts of Sedhiou, Oussouye,
      Bignona and Ziguinchor in Casamance, Senegal. In 2001 the mobile unit performed a
      total of 56 missions and provided examinations to 1273 patients. The main
      indications were pregnancy assessment, amenorrhea, detection of pregnancy,
      painful pelvic tumors and hemorrhage. Findings allowed diagnosis of disorders in
      25% cases. Disorders were pregnancy-related in 47% of cases and gynecological in
      53%. Ultrasound examinations were performed for follow-up purposes in 15% cases,
      for therapeutic purposes in 24% and for referral to the regional hospital center
      in 61%. These findings demonstrate the utility of a mobile ultrasound service in
      managing health problems not only for the community but also for health-care
      structures. This service should be maintained until ultrasound equipment becomes
      available in district hospitals and personnel at those facilities have adequate
      training in ultrasound scanning.

PMID- 17506273
TI  - [Retrospective study of urogenital fistula in Burkina Faso from 2001 to 2003].
AB  - The purpose of this study was to analyze aspects of obstetric urogenital fistulae
      to provide a foundation for implementation of a national control program in
      Burkina Faso. A cross-sectional study with quantitative and qualitative
      components was carried out in 47 hospitals in January 2004. The quantitative
      component consisted of analyzing available data for 2001, 2002 and 2003. The
      qualitative component consisted of interviewing women with fistulae to evaluate
      the impact of the disease on the quality of life and persons in charge of the
      health reference centers to identify the difficulties and needs of the facility.
      In the 3-year study period, 1,500,000 deliveries were attended and 347 fistulae
      were identified in the health reference centers. The incidence rate of obstetric
      fistulae was 23.1 per 100 000 deliveries (CI 95% 20.8-25.7). Women with fistulae
      were young and usually without paid employment. Many had a history of dystocia
      during the labor. Most fistulae were recent, small or average in size and located
      at the level of the vesico-vaginal septum. The failure rate of surgical treatment
      was about 17.5%. Four of the 12 women interviewed reported social alienation and
      ostrasization. Only 4 of the 47 hospitals studied had a personnel qualified to
      manage women with urogenital fistula on a daily basis. One NGO assisted women in
      obtaining care. Proposals for improvement of the situation were considered at a
      national validation workshop. These findings support the need to implement a
      national program that should be evaluated to see lessons learned from this study.

PMID- 17506272
TI  - [Atypical etiology of malaria: local perceptions and practices for treatment and
      prevention in the department of Gaoua, Burkina Faso].
AB  - Malaria is still a public health problem in many sub-Saharan countries. This
      study was undertaken to understand and analyze the relationship between local
      perceptions of malaria and practices for prevention and management in the
      department of Gaoua in Burkina Faso. The goal was to improve the effectiveness of
      prevention and management of malaria in the target population, i.e., children
      under the age of five. Individual interviews and focus groups using a semi
      structured guide were carried out with mothers, traditional healthcare providers
      and elderly persons in four villages of the department of Gaoua. Findings showed
      that practices used for treatment and prevention were directly related to
      perceptions about malaria. Due to poverty, inadequate health service delivery and
      ignorance, people do not always seek medical attention and express doubts about
      the efficacy of modern care. Endogenous practices for malaria prevention are
      directly related to causes described by the population. Modern preventive
      techniques are not used by the population. For instance nets are misused to
      protect corpses from flies or for shelter during funerals.

PMID- 17506274
TI  - [Epidemiologic study on patrons of traditional drink establishments
      (Bandjidromes) in Abidjan, Ivory Coast and surrounding areas].
AB  - This transverse descriptive study was conducted over a three-month period from
      January 10 to April 10, 2003. Findings demonstrated a clear profile of 120
      patrons of traditional drinking establishments called n the city of Abidjan and
      surrounding areas in the Ivory Coast. All subjects interrogated were male. Mean
      age was 31.1 years. Almost all subjects interrogated (99.2%) were of Ivory Coast
      nationality. The main ethnic group was Akan (86.7%) from Baoule (60%). More than
      a third (35.9%) of subjects interviewed were unemployed. Most (62.5%) were
      single. All subjects interrogated stated that they attended "bandjidromes" to
      drink palm wine although other alcoholic beverages were served. However only 9.2%
      of subjects drank only palm wine. The euphoric effect of alcohol and friendly
      atmosphere of the drinking establishment were the main reasons for attendance
      (53.3%). Most persons interrogated (63.3%) had been consuming alcohol for more
      than 10 years. More than half (55%) spent less than three hours a day drinking
      alcoholic beverages. Daily consumption of palm wine ranged from two to four
      liters for most atrons (76.7%). Only 2.5% (3/120) presented neuropsychiatric
      disturbances. These results could be useful in the fight against alcoholism.

PMID- 17506275
TI  - [Precancerous lesions of the uterine cervix in Pointe-Noire, Congo].
AB  - The purpose of this study was to determine the cytological profile and risk
      factors for intraepithelial precancerous lesions of the uterine cervix in an
      urban community of Pointe-Noire, an industrialized seaport located in the
      southeast region of Congo-Brazzaville. A transverse study was carried out over a
      period of 18 months (January 2003 to July 2004) in the Center for the Study of
      Human and Animal Diseases (CSHAD) at the General Adolphe Sie Hospital in Pointe
      Noire. A total of 1347 files of women benefiting from cervico-vaginal smears were
      included in the study. Testing was undertaken either at the request of the
      patient (voluntary screening) or at the request of a health care provider
      (physician, midwife or nurse) in relation with various gynecological problems.
      The relative frequency of intraepithelial lesions was estimated to be 15.36%
      including 9.17% of low-grade intraepithelial lesions (Ig IEL) and 6.19% of high
      grade intraepithelial lesions (hg IEL). The mean age of patients with hg IEL was
      42.25 years (range, 12 to 17). Study of the interval between actual age at the
      time of sample collection and age of first sexual relations showed that women
      presenting IEL had an interval of at least 20 years. This interval probably
      corresponds to the time necessary for the interaction between human
      papillomavirus (HPV) and epithelial cells of the uterine cervix to induce
      intraepithelial lesions that lead to development of cancer of the uterine cervix.
      Comparative analysis of the number of sexual partners between the group of women
      with normal smears and the group with smears showing hg IEL indicated a clear
      predominance of the mean number of partners in the latter group, i.e., 2 +/- 1,2
      versus 5 +/- 1,8 (p < 0.05). Most IEL were observed in multigestational women who
      accounted for 75.39% with a mean of 6.21 for hg IEL. This preliminary study
      provides a sound factual basis in terms of epidemiological data on these
      precancerous lesions of the uterine cervix in the Kouilou department of Congo
      Brazzaville. These data will serve as benchmarks and guidance for forthcoming
      screening campaigns for early detection of uterine cervix cancer.

PMID- 17506276
TI  - [Primary gastric lymphoma complicating HIV infection].
AB  - This report describes a case of non-Hodgkin's lymphoma in a 31-year-old patient
      in whom HIV infection was subsequently diagnosed. The woman consulted for
      epigastralgia. Her medical history included gastritis caused by Helicobacter
      pylori that was given specific treatment. Clinical examination demonstrated type
      III splenomegaly and blood film examination demonstrated hypochromic microcytic
      anemia and neutropenia. Outcome was rapidly fatal and the patient died before
      start up of anti-retroviral therapy. This case suggests that a possible link
      between HIV and/or Helicobacter pylori and lymphomagenesis.

PMID- 17506277
TI  - [Late-occurring cutaneous vasculitis after successful treatment of diffuse
      lepromatous leprosy: Lucio's phenomenon].
AB  - O Lucio's phenomenon is an uncommon type 2 reactional state occurring exclusively
      in patients with diffuse lepromatous leprosy (Lucio-Latapi leprosy). Previous
      case reports have been most frequent in Central America and rare in Asia and
      Africa. Lucio's phenomenon is characterized by necrotic ulcerations of the skin
      preferentially on the lower extremities usually in association with ongoing Lucio
      lepromatosis. The purpose of this report is to describe an unusual case of
      Lucio's phenomenon occurring four years after successful treatment of diffuse
      lepromatous leprosy. The patient was a 51-year-old man who had presented diffuse
      lepromatous leprosy ongoing since 1998. Diagnosis was documented based on
      histological and bacteriologic evidence. After successful treatment using dapsone
      (100 mg/d), rifadine (600 mg/month) and ethionamide (250 mg/d), the patient was
      lost from follow-up for 4 years. In January 2005, he consulted again for
      alteration of general status. Clinical examination showed inflammatory livedo on
      the lower extremities in association with several infiltrating maculo-papular
      lesions and painful erythemato-pupuric lesions on the legs and buttocks. The
      patient's skin was dry, shiny and galabrous with alopecia of the eyelashes and
      eyebrows. Examination of smear samples (skin and nasal) to identify mycobacterium
      leprae was negative. Histological study demonstrated epidermic necrosis with
      aspects of leucocytoclastic vasculitis. No Virchow cells were detected and Ziehl
      staining was negative. Search for circulating immune complexes and
      antiphospholipid antibodies was negative. Diagnosis of Lucio's phenomenon was
      made and the patient was treated using prednisone at a dose of 1 mg/kg/d in
      association with rifampicine (600 mg/month) and dapsone (100 mg/d). Outcome was
      favorable after one month of treatment. Lucio's phenomenon has rarely been
      observed in Tunisia. To our knowledge this is the third case reported from
      Tunisia and only 13 cases have been reported in the world since 1983. In all
      cases including the two from Tunisia, Lucio's phenomenon occurred during the
      course of treatment of ongoing Lucio-Latapi lepromatous leprosy (2). The
      remarkable features of our case are that Lucio's phenomenon occurred a long time
      after successful treatment of lepromatous leprosy and that the patient responded
      promptly to treatment. The pathogenesis of Lucio's phenomenon is often compared
      with that of erythema nodosum leprosum. Discussion focuses on pathophysiologic
      features and natural course of Lucio's phenomenon.

PMID- 17506278
TI  - [Recurrent chromomycosis of the face and extremities: first case report from
      Iibya].
AB  - Chromomycosis is a chronic cutaneous fungal infection most prevalent in tropical
      and subtropical countries. It mainly affects adults working in rural areas. This
      purpose of this report is to describe the first cases in Libya in a 16-year-old
      girl. This case is also remarkable with regard to location on the face and
      members, lack of association with trauma and long delay for recurrence, i.e., 6
      years after first occurrence.

PMID- 17506279
TI  - [Treatment of visceral leishmaniasis in children].
AB  - Visceral Leishmania infantum leishmaniasis is endemic in the south of France. For
      many years the mainstay for treatment of infected children was pentavalent
      antimony: meglumine antimoniate (Glucantime) or sodium stibogluconate
      (Pentostam). However these drugs are poorly tolerated and resistance similar to
      that observed in the treatment of Indian visceral Leishmania donovani
      leishmaniasis has been reported. Currently liposomal amphotericin B is being used
      instead of antimony for treatment of visceral leishmaniasis in children in
      France. In addition to being well tolerated, liposomal amphotericin B is almost
      100% effective. It can be administered in six intravenous injections of 3-4 mg/kg
      each (days 1 to 5 then day 10). A two-day protocol (10 mg/kg/d) that would reduce
      overall cost by shortening the duration of hospitalization is now being studied.
      Another oral drug, i.e., miltefosine, has been successfully used for treatment of
      visceral leishmaniasis in India. However it has not been evaluated for treatment
      of Mediterranean visceral leishmaniasis.

PMID- 17506280
TI  - [Mediterranean leishmaniasis caused by Leishmania infantum. Update on the utility
      of the IT-Leish and ID-Pagia leishmaniasis tests].
AB  - The purpose of this article is to update information about Mediterranean
      leishmaniasis caused by Leishmania infantum in man and about the canine
      reservoir. Special emphasis is placed on laboratory diagnosis tests for
      Mediterranean visceral leishmaniasis (MVL) in humans. In addition two rapid
      diagnostic tests for human leishmaniasis are compared based on indirect
      immunofluorescence and Western blot. Findings show that the overall sensitivity
      of the two tests in immunocompetent and immunodepressed patients ranged from 54%
      to 97%, a specificity of 97%, with positive predictive value ranging from 75% to
      97% and a negative predictive value of around 95%. For diagnosis of cutaneous
      leishmaniasis, positivity of these tests in one case out of 2 underscores the
      predictive value of a positive test.

PMID- 17506281
TI  - [Cyclines and malaria].
AB  - The emergence and rapid spread of Plasmodium falciparum resistance to various
      antimalarials compounds is gradually reducing the clinician's options for
      treating malaria and for adapting prophylaxis to each traveler and destination.
      In this context doxycycline is an increasingly useful alternative except in
      individuals with contraindications, mainly children under the age of eight and
      pregnant women. Already used successfully in association with quinine for
      treatment of malaria in areas with multiresistance, doxycline has also proven to
      be effective and well tolerated for prophylaxis of malaria. No resistance to
      doxycycline has been observed to date. Most reported prophylactic failures have
      been related to poor compliance during the month following return from the
      endemic zone. The mechanisms of action of doxycycline on the parasite are still
      unclear. Identification of the molecular targets of doxycycline would open the
      way for the design of more active structural analogues with longer half-life.

PMID- 17506282
TI  - [Hemoperitoneum due to spontaneous rupture of the spleen during malaria].

PMID- 17506283
TI  - [Clustered cases of urinary and intestinal bilharziasis in French military
      personnel].

PMID- 17506284
TI  - [Ophthalmologic manifestations of leprosy: findings in two cases in Tunisia].

PMID- 17506285
TI  - Early influence of the steppe tribes in the peopling of Siberia.
AB  - The Yakuts, Middle Age Turkic speakers (15th-16th centuries), are widely accepted
      as the first settlers of the Altai-Baikal area in eastern Siberia. They are
      supposed to have introduced horses and developed metallurgy in this geographic
      area during the 15th or 16th century A.D. The analysis of the Siberian grave of
      Pokrovsk, recently discovered near the Lena River (61 degrees 29' N) and dated by
      accelerator mass spectrometry from 2,400 to 2,200 years B.P., may provide new
      elements to test this hypothesis. The exceptional combination of various
      artifacts and the mitochondrial DNA data extracted from the bone remains of the
      Pokrovsk man might prove the existence of previous contacts between autochthonous
      hunters of Oriental Siberia and the nomadic horse breeders from the Altai-Baikal
      area (Mongolia and Buryatia). Indeed, the stone arrowhead and the harpoons relate
      this Pokrovsk man to the traditional hunters of the Taiga. Some artifacts made of
      horse bone and the pieces of armor, however, are related to the tribes of
      Mongolia and Buryatia of the Xiongnu period (3rd century B.C.). This affinity has
      been confirmed by the match of the mitochondrial haplotype of this subject with a
      woman of the Egyin Gol necropolis (Mongolia, 2nd/3rd century A.D.) as well as
      with two modern Buryats. This result allows us to postulate that contacts between
      southern steppe populations and Siberian tribes occurred before the 15th century.

PMID- 17506286
TI  - Genetic structure analysis of three Hispanic populations from Costa Rica, Mexico,
      and the southwestern United States using Y-chromosome STR markers and mtDNA
      sequences.
AB  - Two hundred seventeen male subjects from Costa Rica, Mexico, and the Hispanic
      population of the southwestern United States were studied. Twelve Y-chromosome
      STRs and the HVSI sequence of the mtDNA were analyzed to describe their genetic
      structure and to compare maternal and paternal lineages. All subjects are part of
      two NIMH-funded studies to localize schizophrenia susceptibility genes in
      Hispanic populations of Mexican and Central American ancestry. We showed that
      these three populations are similar in their internal genetic characteristics, as
      revealed by analyses of mtDNA and Y-chromosome STR diversity. These populations
      are related through their maternal lineage in a stronger way than through their
      paternal lineage, because a higher number of shared haplotypes and polymorphisms
      are seen in the mtDNA (compared to Y-chromosome STRs). These results provide
      evidence of previous contact between the three populations and shared histories.
      An analysis of molecular variance revealed no genetic differentiation for the
      mtDNA for the three populations, but differentiation was detected in the Y
      chromosome STRs. Genetic distance analysis showed that the three populations are
      closely related, probably as a result of migration between close neighbors, as
      indicated by shared haplotypes and their demographic histories. This relationship
      could be an important common feature for genetic studies in Latin American and
      Hispanic populations.

PMID- 17506287
TI  - Y-chromosome-Specific STR haplotype data on the Rapanui population (Easter
      Island).
AB  - Located in the south Pacific Ocean, Rapanui is one of the most isolated inhabited
      islands in the world. Cultural and biological data suggest that the initial
      Rapanui population originated from central Polynesia, although the presence of
      foreign or exotic genes in the contemporary population, as a result of admixture
      with Europeans and/or South Americans during the last two centuries, also has to
      be considered. To estimate the genetic affinities of the Rapanui population with
      neighboring populations, we analyzed seven microsatellite polymorphisms of the Y
      chromosome that recently have been indicated as useful in the study of local
      population structure and recent demographic history. Phylogenetic analysis of
      Rapanui Y-chromosome haplotypes identified two clusters. The largest cluster
      contained 60% of all haplotypes and is characterized, in particular, by the
      presence of the DYS19*16, DYS390*20, and DYS393*14 alleles, a combination found
      frequently in Western Samoa. The second cluster is characterized by the presence
      of the DYS19*14, DYS390*24, and DYS393*13 alleles, and these have a relatively
      high frequency in European and European-derived populations but are either
      infrequent or absent in native Pacific populations. In addition to the two
      clusters, one male is of haplogroup Q*, which is indicative of native American
      ancestry. The genetic structure of the current male population of Rapanui is most
      likely a product of some genetic contribution from European and South American
      invaders who mated with the indigenous Polynesian women. However, analysis of
      Rapanui's relationships with other Pacific and Asian populations indicates that,
      as in Western Samoa and Samoa, the population has experienced extreme drift and
      founder events.

PMID- 17506288
TI  - FMR1 CGG repeat distribution and linked microsatellite-SNP haplotypes in normal
      Mexican Mestizo and indigenous populations.
AB  - The (CGG)n repeat size distribution in the FMR1 gene was studied in healthy
      individuals: 80 X chromosomes of Mexican Mestizos from Mexico City and 33 X
      chromosomes of Mexican Amerindians from three indigenous communities (Purepechas,
      Nahuas, and Tzeltales), along with alleles and haplotypes defined by two
      microsatellite polymorphic markers (DXS548 and FRAXAC1) and two single nucleotide
      polymorphisms (FMRA and FMRB). Genetic frequencies of Mestizo and Amerindian
      subpopulations were statistically similar in almost all cases and thus were
      considered one population for comparisons with other populations. Sixteen (CGG)n
      alleles in the 17-38 size range were observed, and the most common were the 25
      (38.0%), 26 (28.3%), and 24 (12.3%) repeat alleles. This pattern differs from
      most other populations reported, but a closer relation to Amerindian, European,
      and African populations was found, as expected from the historical admixture that
      gave rise to Mexican Mestizos. The results of the CA repeats analysis at DXS548
      FRAXAC1 were restricted to nine haplotypes, of which haplotypes 7-4 (52.2%), 8-4
      (23.8%), and 7-3 (11.5%) were predominant. The modal haplotype 7-4, instead of
      the nearly universal haplotype 7-3, had been reported exclusively in Eastern
      Asian populations. Likewise, only seven different FRAXAC1-FMRA-FMRB haplotypes
      were observed, including five novel haplotypes (3TA, 4TA, 3 - A, 4 - A, and 5 -
      A), compared with Caucasians. Of these, haplotypes - A (78.7%) and 3 - A (13.2%)
      were the most common in the Mexican population. These data suggest a singular but
      relatively low genetic diversity at FMR1 in the studied Mexican populations that
      may be related to the recent origin of Mestizos and the low admixture rate of
      Amerindians.

PMID- 17506289
TI  - Autosomal STR variation in a Basque population: Vizcaya Province.
AB  - We have characterized 68 unrelated Basque individuals from Vizcaya, Spain, for 13
      tetrameric short tandem repeat (STR) loci: CSF1PO, D3S1358, D5S818, D7S820,
      D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, TPOX, and VWA.
      Interpopulational analyses were also performed for 21 European and North African
      population data sets for nine of the STRs typed in the Basque sample.
      Heterozygosity values for the Vizcayan Basques were found to be high, ranging
      from 0.662 to 0.882, and none of the STR loci significantly deviated from Hardy
      Weinberg equilibrium. Based on the comparative population data set, the average
      G(ST) score is 0.7%, indicating a low degree of genetic differentiation. However,
      neighbor-joining trees and multidimensional-scaling plots of D(A) genetic
      distances indicate that the Vizcayan Basques are an outlier relative to both
      neighboring Iberians and North African populations.

PMID- 17506290
TI  - Time series analysis of the epidemiological transition in Minorca, 1634-1997.
AB  - Autoregressive integrated moving average (ARIMA) models provide a powerful tool
      for detecting seasonal patterns in mortality statistics. The strength of ARIMA
      models lies in their ability to reveal complex structures of temporal
      interdependence in time series. Moreover, changes in model parameters provide an
      empirical basis for detecting secular trends and death seasonality patterns. This
      approach is illustrated by our analysis of changes in the mortality patterns of
      the population of the town of Es Mercadal on the island of Minorca between 1634
      and 1997. These data reveal a transition from an early mortality pattern
      requiring a complex ARIMA model that accounts for a strong seasonal death pattern
      and periodic epidemic-related mortality crises to a much simpler 20th-century
      pattern that can be described by a simple single-parameter ARIMA model. These
      same data were also analyzed using standard seasonality tests. The results show
      that the reduction in the number of parameters required to fit the Es Mercadal
      mortality data coincides with the epidemiological transition in which the
      predominant causes of morbidly and mortality shift from infectious to
      degenerative causes.

PMID- 17506291
TI  - Y-chromosomal evidence for a founder effect in Mbya-guarani Amerindians from
      northeast Argentina.
AB  - To assess the paternal history of the Mbya-Guarani Amerindians of northeast
      Argentina, we examined the genetic variation in seven Y-chromosome loci: the
      binary marker M3 at locus DYS199, and six short tandem repeats (DYS19, DYS389I,
      DYS389II, DYS390, DYS391, and DYS393). The most striking finding is the high
      frequency among the Mbya-Guarani of Q3 lineages with the usually rare alleles
      DYS391*11 and DYS393*11, which could be the result of a founder effect, given the
      recent history of the population.

PMID- 17506292
TI  - [Heart rate as a therapeutic target for stable angina. Role of anti-ischemic
      agents and their underuse in Italy].
AB  - Several epidemiological studies showed that heart rate is associated with a high
      morbidity and mortality rate in the general population and in subjects affected
      by different cardiovascular diseases. Particularly relevant is the role of heart
      rate in patients with stable angina, a clinical condition that affects mainly 40
      000 patients per one million people. The treatment of stable angina is focused
      more on symptom improvement than on decrease of mortality. In this context, beta
      blockers are usually recommended for these patients, since, reducing heart rate
      and blood pressure, favorably influence clinical symptoms. However, data from
      registries show that nearly one third of patients with stable angina do not
      receive beta-blockers for specific contraindications or intolerance. For these
      patients, new perspectives of treatment might be available with the use of a new
      class of drugs, the inhibitors of the I(f) channels, which selectively reduce
      heart rate without interfering with other pathophysiological mechanisms.

PMID- 17506293
TI  - [Permanent atrial fibrillation and heart failure: radiofrequency ablation of
      atrioventricular junction and cardiac resynchronization therapy: review of the
      literature and of the new techniques for echocardiographic assessment].
AB  - Radiofrequency ablation of atrioventricular junction plus pacing therapy ("ablate
      and pace") is an effective non-pharmacological therapy in patients with medically
      refractory permanent atrial fibrillation and heart failure. However, the chronic
      right ventricular pacing may result in regional wall motion abnormalities and
      adverse hemodynamic effects. These findings imply that patients with permanent
      atrial fibrillation who undergo "ablate and pace" may benefit from cardiac
      resynchronization therapy. The review of both observational and randomized
      studies suggests an important role of biventricular pacing combined with
      atrioventricular junction ablation only in patients with severe reduction of left
      ventricular ejection fraction and advanced heart failure. In all other patients
      with permanent atrial fibrillation, the comparison of conventional right
      ventricular pacing with respect to cardiac resynchronization therapy showed
      conflicting results. The assessment of cardiac dyssynchrony by means of new
      echocardiographic technology, including three-dimensional analysis, may improve
      the selection of the best pacing modality in patients undergoing "ablate and
      pace" for drug refractory permanent atrial fibrillation.

PMID- 17506294
TI  - [Evaluation of atrial function by echocardiography].
AB  - In cardiology, ventricular function has extensively been studied, whereas atrial
      function received less attention. For such a reason atrial function is less
      known. The aim of this review was to summarize the role of atrial function and to
      explain how echocardiography and new echocardiographic-derived techniques may be
      of help to better study atrial function.

PMID- 17506295
TI  - [Urocortin: molecular biology and cardiovascular effects].
AB  - Urocortins and the corticotropin releasing hormone have a long evolutionary
      history. In the nervous system the corticotropin releasing hormone is responsible
      of anxiogenic effects associated with stress, while urocortins are concerned with
      adaptive behavior. Urocortins are also expressed in the heart, where they may
      play an autocrine/paracrine role binding to corticotropin releasing hormone-R2
      receptors. The expression of endogenous cardiac urocortin is increased by in
      vitro ischemia-reperfusion damage, and the addiction of exogenous urocortins is
      associated with reduction of myocardial cell death during ischemia-reperfusion
      damage in vitro, ex vivo and in vivo. In isolated perfused heart urocortin
      enhances cardiac contractility and decreases high energy phosphates reduction
      after ischemia-reperfusion damage. Urocortin is also associated with peripheral
      and coronary vasodilation and with positive inotropic effect. There are
      experimental data which suggest a beneficial effect of urocortins in subjects
      with heart failure and a possible beneficial role of urocortin in preventing the
      iatrogenic ischemia-reperfusion damage caused by cardioplegic arrest during
      cardiac surgery. These early observations suggest that assessment of the clinical
      use of urocortin in heart failure and for the prevention of ischemia-reperfusion
      damage in cardiac surgery should be actively pursued.

PMID- 17506296
TI  - [Usefulness of a telematic system and image analysis in the follow-up of high
      risk patients: a new health service model].
AB  - BACKGROUND: Inadequate blood pressure control in hypertensive patients is in
      contrast with the evidence from clinical studies of effectiveness of the same
      antihypertensive compounds used in clinical practice. These results may be due to
      follow-up management of hypertensive patients and in particular to the
      interaction between general practitioners (GPs) and hypertension specialists. The
      aim of this study was to assess the effectiveness of an internet-based digital
      network, connecting specialists and GPs in the Campania Region, on blood pressure
      control and major cardiovascular events. METHODS: A network between the
      Hypertension Center of "Federico II" University, 14 specialist centers and 60 GPs
      was done in the Campania Region (Campania Salute Project, CS). Randomized GPs
      enrolled in CS could update online clinic records of patients (n = 1979). As a
      control group, we included 2045 patients referred to the specialist centers by
      GPs from outside the network. All patients completed a 2-year follow-up. RESULTS:
      CS determined a significant reduction in systolic and diastolic blood pressure
      (CS group 144 +/- 18/91 +/- 11 vs 136 +/- 17/86 +/- 10 mmHg; control group 144 +/
      17/90 +/- 10 vs 139 +/- 15/87 +/- 9 mmHg, p < 0.001). Indeed, the CS group
      showed less frequent fatal and non-fatal major cardiovascular events (2.9 vs
      4.3%, chi2 = 5.047, p < 0.02). CONCLUSIONS: Our results support the hypothesis
      that telematic connections may contribute to improve blood pressure control and
      reduce major cardiovascular events.

PMID- 17506297
TI  - [Bentall operation after previous repair of tetralogy of Fallot].
AB  - Pathologies that involve the ascending aorta are described in case reports of
      patients after complete repair of tetralogy of Fallot. Here, we present a case
      report. Preoperative tests showed an aortic ratio of > 1.5. The patient was
      operated on replacement of the ascending aorta according to the Bentall
      technique. At present, the guidelines for replacement of the ascending aorta
      recommend an aortic ratio of > 1.5 and in case of Marfan syndrome of > 1.3. In
      these patient subsets, cystic medial necrosis and an increased risk of aortic
      dissection have been described. Therefore, as for Marfan syndrome, why an aortic
      ratio of >1.3 should not be considered a proper surgical indication also for
      these patients?

PMID- 17506298
TI  - [Hypothermia in the elderly: a shivering case].
AB  - Hypothermia is a medical emergency in patients with a body temperature lower than
      35 degrees C (95 degrees F) due to prolonged exposure to ambient cold
      temperatures without appropriate protection. This condition has a 5-fold
      increased risk of death in the elderly. Usually, diagnosis is suggested by
      warning signs and symptoms like lethargy, weakness and loss of coordination,
      confusion and reduced respiratory or heart rate. We report the case of a 76-year
      old woman who was referred to our center for symptomatic sinus bradycardia and
      with typical electrocardiographic abnormalities (Osborn wave) that suggested the
      diagnosis of severe hypothermia.

PMID- 17506299
TI  - [Progress in diagnosis and therapy: Calcium-phosphorus metabolism disorders].

PMID- 17506300
TI  - [Differential diagnosis of hypercalcemia].

PMID- 17506301
TI  - [Progress in diagnosis and therapy: Hypercalcemia due to primary
      hyperparathyroidism].

PMID- 17506302
TI  - [Progress in therapy and diagnosis: Hypercalcemia due to parathyroid hormone
      related protein producing neoplasms].

PMID- 17506303
TI  - [Progress in diagnosis and therapy: Hypercalcemia due to multiple myeloma and
      wide-spread neoplastic bone metastasis].

PMID- 17506304
TI  - [Progress in diagnosis and therapy: familial hypocalciuric hypercalcemia].

PMID- 17506305
TI  - [Progress in diagnosis of and therapy for hypocalcemia: Differential diagnosis
      and classification of hypoparathyroidism].

PMID- 17506306
TI  - [Progress in diagnosis and therapy: Hypocalcemia due to idiopathic
      hypoparathyroidism].

PMID- 17506307
TI  - [Progress in diagnosis and therapy: Calcium sensing receptor gene abnormality and
      hypoparathyroidism].

PMID- 17506308
TI  - [Progress in diagnosis and therapy: Hypocalcemia due to idiopathic
      hypoparathyroidism].

PMID- 17506309
TI  - [Progress in diagnosis and therapy: Hypocalcemia due to
      pseudohypoparathyroidism].

PMID- 17506310
TI  - [Regulation of phosphorus-vitamin D metabolism by FGF23].

PMID- 17506311
TI  - [X-linked hypophosphatemic rickets].

PMID- 17506312
TI  - [Tumor-induced hypophosphatemic osteomalacia].

PMID- 17506313
TI  - [Vitamin D-dependent rickets type I, II].

PMID- 17506314
TI  - [Vitamin D deficiency and vitamin D insufficiency].

PMID- 17506315
TI  - [Calcium-phosphorus metabolic disorders and the primary care (discussion)].

PMID- 17506316
TI  - [Basedow disease with recurrent syncopal attack and severe pulmonary
      hypertension].

PMID- 17506317
TI  - [Unsuccessful management for renal failure induced by glycogen storage disease
      type-I (Von Gierke disease) in peritoneal dialysis].

PMID- 17506318
TI  - [Saved case of purpura fulminans in pneumococcal sepsis after splenectomy].

PMID- 17506319
TI  - [Peripheral lung cancer effectively diagnosed with virtual bronchoscopy].

PMID- 17506320
TI  - [Nocturnal epilepsy associated with sleep apnea syndrome].

PMID- 17506321
TI  - [Recent therapeutic strategy for follicular lymphoma].

PMID- 17506322
TI  - [Treatment for symptoms of pseudoaldosteronism].

PMID- 17506323
TI  - [Threat from newly emerging influenza].

PMID- 17506324
TI  - [Diagnosis of and therapy for pancreatic neoplasms].

PMID- 17506325
TI  - [Reality in clinical trials lead by physicians].

PMID- 17506326
TI  - Functional analysis of lipid metabolism in Magnaporthe grisea reveals a
      requirement for peroxisomal fatty acid beta-oxidation during appressorium
      mediated plant infection.
AB  - The rice blast fungus Magnaporthe grisea infects plants by means of specialized
      infection structures known as appressoria. Turgor generated in the appressorium
      provides the invasive force that allows the fungus to breach the leaf cuticle
      with a narrow-penetration hypha gaining entry to the underlying epidermal cell.
      Appressorium maturation in M. grisea involves mass transfer of lipid bodies to
      the developing appressorium, coupled to autophagic cell death in the conidium and
      rapid lipolysis at the onset of appressorial turgor generation. Here, we report
      identification of the principal components of lipid metabolism in M. grisea based
      on genome sequence analysis. We show that deletion of any of the eight putative
      intracellular triacylglycerol lipase-encoding genes from the fungus is
      insufficient to prevent plant infection, highlighting the complexity and
      redundancy associated with appressorial lipolysis. In contrast, we demonstrate
      that a peroxisomally located multifunctional, fatty acid beta-oxidation enzyme is
      critical to appressorium physiology, and blocking peroxisomal biogenesis prevents
      plant infection. Taken together, our results indicate that, although
      triacylglycerol breakdown in the appressorium involves the concerted action of
      several lipases, fatty acid metabolism and consequent generation of acetyl CoA
      are necessary for M. grisea to complete its prepenetration phase of development
      and enter the host plant.

PMID- 17506327
TI  - OsWRKY13 mediates rice disease resistance by regulating defense-related genes in
      salicylate- and jasmonate-dependent signaling.
AB  - Although 109 WRKY genes have been identified in the rice genome, the functions of
      most are unknown. Here, we show that OsWRKY13 plays a pivotal role in rice
      disease resistance. Overexpression of OsWRKY13 can enhance rice resistance to
      bacterial blight and fungal blast, two of the most devastating diseases of rice
      worldwide, at both the seedling and adult stages, and shows no influence on the
      fertility. This overexpression was accompanied by the activation of salicylic
      acid (SA) synthesis-related genes and SA-responsive genes and the suppression of
      jasmonic acid (JA) synthesis-related genes and JA-responsive genes. OsWRKY13
      bound to the promoters of its own and at least three other genes in SA- and JA
      dependent signaling pathways. Its DNA-binding activity was influenced by pathogen
      infection. These results suggest that OsWRKY13, as an activator of the SA
      dependent pathway and a suppressor of JA-dependent pathways, mediates rice
      resistance by directly or indirectly regulating the expression of a subset of
      genes acting both upstream and downstream of SA and JA. Furthermore, OsWRKY13
      will provide a transgenic tool for engineering wider-spectrum and whole-growth
      stage resistance rice in breeding programs.

PMID- 17506328
TI  - A nonribosomal peptide synthetase gene (mgoA) of Pseudomonas syringae pv.
      syringae is involved in mangotoxin biosynthesis and is required for full
      virulence.
AB  - Pseudomonas syringae pv. syringae, which causes the bacterial apical necrosis of
      mango, produces the antimetabolite mangotoxin. We report here the cloning,
      sequencing, and identity analysis of a chromosomal region of 11.1 kb from strain
      P syringae pv. syringae UMAF0158, which is involved in mangotoxin biosynthesis.
      This chromosomal region contains six complete open reading frames (ORFs),
      including a large gene (ORF5) with a modular architecture characteristic of
      nonribosomal peptide synthetases (NRPS) named mgoA. A Tn5 mutant disrupted in
      mgoA was defective in mangotoxin production, revealing the involvement of the
      putative NRPS gene in the biosynthesis of mangotoxin. This derivative strain
      impaired in mangotoxin production also showed a reduction in virulence as
      measured by necrotic symptoms on tomato leaflets. Mangotoxin production and
      virulence were restored fully in the NRPS mutant by complementation with plasmid
      pCG2-6, which contains an 11,103-bp chromosomal region cloned from the wild-type
      strain P syringae pv. syringae UMAF0158 that includes the putative NPRS gene
      (mgoA). The results demonstrate that mgoA has a role in the virulence of P.
      syringae pv. syringae. The involvement of an NRPS in the production of an
      antimetabolite toxin from P. syringae inhibiting ornithine acetyltransferase
      activity is proposed.

PMID- 17506329
TI  - Developmental transcript profiling of cyst nematode feeding cells in soybean
      roots.
AB  - Cyst nematodes of the genus Heterodera are obligate, sedentary endoparasites that
      have developed highly evolved relationships with specific host plant species.
      Successful parasitism involves significant physiological and morphological
      changes to plant root cells for the formation of specialized feeding cells called
      syncytia. To better understand the molecular mechanisms that lead to the
      development of nematode feeding cells, transcript profiling was conducted on
      developing syncytia induced by the soybean cyst nematode Heterodera glycines in
      soybean roots by coupling laser capture microdissection with high-density
      oligonucleotide microarray analysis. This approach has identified pathways that
      may play intrinsic roles in syncytium induction, formation, and function. Our
      data suggest interplay among phytohormones that likely regulates synchronized
      changes in the expression of genes encoding cell-wall-modifying proteins. This
      process appears to be tightly controlled and coordinately regulated with cell
      wall rigidification processes that may involve lignification of feeding cell
      walls. Our data also show local downregulation of jasmonic acid biosynthesis and
      responses in developing syncytia, which suggest a local suppression of plant
      defense mechanisms. Moreover, we identified genes encoding putative transcription
      factors and components of signal transduction pathways that may be important in
      the regulatory processes governing syncytium formation and function. Our analysis
      provides a broad mechanistic picture that forms the basis for future hypothesis
      driven research to understand cyst nematode parasitism and to develop effective
      management tools against these pathogens.

PMID- 17506330
TI  - Twitching motility is essential for endophytic rice colonization by the N2-fixing
      endophyte Azoarcus sp. strain BH72.
AB  - Azoarcus sp. strain BH72, as an endophyte of grasses, depends on successful host
      colonization. Type IV pili are essential for mediating the initial interaction
      with rice roots. In the genome sequence analysis, the pilT gene was identified,
      which encodes for a putative type IV pilus retraction protein. PilT of Azoarcus
      sp. BH72 shares high similarity to PilT of the human pathogen Pseudomonas
      aeruginosa PAO1 (77% amino acid sequence identity) and contains a predicted
      nucleotide-binding motif. To gain more insights into the role of the type IV pili
      in the colonization process of Azoarcus spp., we constructed an insertional
      mutant of pilT and a deletion mutant of pilA, the major structural component of
      the pilus structure. The pilT mutant, as the pilin deletion mutant deltapilA, was
      abolished in twitching motility. Western blot analyses and electron microscopy
      studies demonstrated an enhanced piliation of the Azoarcus pilT mutant strain
      compared with the wild type, indicating that, indeed, PilT has a role in pilus
      retraction. Studies on rice root colonization in gnotobiotic cultures revealed
      that the establishment of microcolonies on the root surface was strongly reduced
      in the deltapilA mutant, whereas the surface colonization was reduced by only 50%
      in the nontwitching pilT mutant. However, endophytic colonization of rice roots
      was strongly reduced in both mutants. These results demonstrate that the
      retractile force mediated by PilT is not essential for the bacterial colonization
      of the plant surface, but that twitching motility is necessary for invasion of
      and establishment inside the plant. Thus, a novel determinant for endophytic
      interactions with grasses was identified.

PMID- 17506331
TI  - Molecular and pathotypic characterization of new Xanthomonas oryzae strains from
      West Africa.
AB  - DNA polymorphism analysis and pathogenicity assays were used to characterize
      strains of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola
      collected from rice leaves in West Africa. Restriction fragment length
      polymorphism (RFLP), repetitive sequence-based polymerase chain reaction,
      fluorescent amplified fragment-length polymorphism (FAFLP) analyses were assessed
      for molecular characterization, while pathogenicity was tested by leaf clipping
      and leaf infiltration. Dendrograms were generated for the data sets obtained from
      RFLP analysis and repetitive polymerase chain reaction suggesting that the
      interrelationships between strains were dependent on the technique used. In all
      cases, data showed that African strains of X. oryzae pv. oryzae form a group
      genetically distant from Asian strains. FAFLP analyses separated the X. oryzae
      strains into three groups with significant bootstrap values. A specific and
      intriguing feature of African strains of X. oryzae pv. oryzae is a reduction in
      the number of insertion sequence elements and transcription activator-like
      (avrBs3/pthA) effector genes, based on the molecular markers employed in the
      study. In addition, pathogenicity assays conducted with African strains of X.
      oryzae pv. oryzae on a series of nearly isogenic lines (NILs) identified three
      new races. Finally, leaf infiltration assays revealed the capacity of African
      strains of X. oryzae pv. oryzae to induce a nonhost hypersensitive response in
      Nicotiana benthamiana, in contrast with Asian X. oryzae pv. oryzae and X. oryzae
      pv. oryzicola strains. Our results reveal substantial differences between genomic
      characteristics of Asian and African strains of X. oryzae pv. oryzae.

PMID- 17506332
TI  - Evidence that the nonstructural protein of Tomato spotted wilt virus is the
      avirulence determinant in the interaction with resistant pepper carrying the TSW
      gene.
AB  - All known pepper cultivars resistant to Tomato spotted wilt virus (TSWV) possess
      a single dominant resistance gene, Tsw. Recently, naturally occurring resistance
      breaking (RB) TSWV strains have been identified, causing major concerns. We used
      a collection of such strains to identify the specific genetic determinant that
      allows the virus to overcome the Tsw gene in Capsicum spp. A reverse genetic
      approach is still not feasible for TSWV; therefore, we analyzed reassortants
      between wild-type (WT) and RB strains. Our results confirmed that the S RNA,
      which encodes both the nucleocapsid protein (N) and a nonstructural protein
      (NSs), carries the genetic determinant responsible for Tsw resistance breakdown.
      We then used full-length S RNA segments or the proteins they encode to compare
      the sequences of WT and related RB strains, and obtained indirect evidence that
      the NSs protein is the avirulence factor in question. Transient expression of NSs
      protein from WT and RB strains showed that they both can equally suppress post
      transcriptional gene silencing (PTGS). Moreover, biological characterization of
      two RB strains carrying deletions in the NSs protein showed that NSs is important
      in maintaining TSWV infection in newly emerging leaves over time, preventing
      recovery. Analysis of another RB strain phenotype allowed us to conclude that
      local necrotic response is not sufficient for resistance in Capsicum spp.
      carrying the Tsw gene.

PMID- 17506333
TI  - Refinement of the Xanthomonas campestris pv. vesicatoria hrpD and hrpE operon
      structure.
AB  - The plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria possesses a
      type III secretion (T3S) system which is encoded in the 23-kb hypersensitive
      response and pathogenicity (hrp) gene cluster. The T3S system is essential for
      pathogenicity in susceptible hosts and the induction of the hypersensitive
      response in resistant plants. In this study, we revisited the operon structure of
      the right part of the hrp gene cluster. Based on complementation experiments of
      transposon insertions and reverse-transcription polymerase chain reaction
      analyses, the hrpD operon contains hrcQ, hrcR, hrcS, and hpaA, whereas hrcD,
      hrpD6, and hrpE belong to the hrpE operon. We determined the transcriptional
      start site of the hrpE operon and showed that there is a promoter upstream of
      hrcD containing a plant-inducible promoter box. Conserved secondary mRNA
      structures in the intergenic region between hrpD6 and hrpE suggest a
      posttranscriptional regulated expression of hrpE. Based on comparisons of
      different hrp gene clusters and the analysis of evolutionary rates, we propose
      that the hrpE transcriptional unit was integrated into the hrp gene cluster at a
      later time.

PMID- 17506334
TI  - A novel role for catalase B in the maintenance of fungal cell-wall integrity
      during host invasion in the rice blast fungus Magnaporthe grisea.
AB  - Asexual spores of the rice blast fungus germinate to produce a specialized and
      melanized infection structure, the appressorium, which is pivotal to successful
      plant penetration. To investigate whether Magnaporthe grisea counteracts the
      toxic burst of H2O2 localized beneath the site of attempted invasion, we examined
      the temporal expression of five candidate antioxidant genes. Of these, the
      putatively secreted large subunit catalase CATB gene was 600-fold up-regulated in
      vivo, coincident with penetration, and moderately up-regulated in vitro, in
      response to exogenous H2O2. Targeted gene replacement of CATB led to compromised
      pathogen fitness; the catB mutant displayed paler pigmentation and accelerated
      hyphal growth but lower biomass, poorer sporulation, fragile conidia and
      appressoria, and impaired melanization. The catB mutant was severely less
      pathogenic than Guy 11 on barley and rice, and its infectivity was further
      reduced on exposure to H2O2. The wild-type phenotype was restored by the
      reintroduction of CATB into the catB mutant We found no evidence to support a
      role for CATB in detoxification of the host-derived H2O2 at the site of
      penetration. Instead, we demonstrated that CATB plays a part in strengthening the
      fungal wall, a role of particular importance during forceful entry into the host.

PMID- 17506335
TI  - The role of a P1-type ATPase from Pseudomonas fluorescens SBW25 in copper
      homeostasis and plant colonization.
AB  - The genome of the plant-colonizing bacterium Pseudomonas fluorescens SBW25
      possesses a putative copper-transporting P1-type ATPase (CueA) that is induced on
      the plant surfaces. Using a chromosomally-integrated cueA-lacZ fusion, we show
      that transcription of cueA can be induced (in vitro) by ions of copper, silver,
      gold, and mercury. To investigate the biological significance of cueA, a nonpolar
      cueA deletion mutant (SBW25 delta cueA) was constructed. This mutant strain
      displayed a twofold reduction in its tolerance to copper compared with the wild
      type strain; however, no change was observed in the sensitivity of the mutant
      strain to silver, gold, or mercury ions. To obtain insight into the ecological
      significance of cueA, the competitive ability of SBW25 delta cueA was determined
      relative to wild-type SBW25 in three environments (none contained added copper):
      minimal M9 medium, the root of sugar beet (Beta vulgaris), and the root of pea
      (Pisum sativum). Results showed that the fitness of SBW25 delta cueA was not
      different from the wild type in laboratory medium but was compromised in the two
      plant environments. Taken together, these data demonstrate a functional role for
      CueA in copper homeostasis and reveal an ecologically significant contribution to
      bacterial fitness in the plant rhizosphere. They also suggest that copper ions
      accumulate on plant surfaces.

PMID- 17506336
TI  - The MAP kinase kinase MKK2 affects disease resistance in Arabidopsis.
AB  - The Arabidopsis mitogen-activated protein kinase (MAPK) kinase 2 (MKK2) was shown
      to mediate cold and salt stress responses through activation of the two MAP
      kinases MPK4 and MPK6. Transcriptome analysis of plants expressing constitutively
      active MKK2 (MKK2-EE plants) showed altered expression of genes induced by
      abiotic stresses but also a significant number of genes involved in defense
      responses. Both MPK4 and MPK6 became rapidly activated upon Pseudomonas syringae
      pv. tomato DC3000 infection and MKK2-EE plants showed enhanced levels of MPK4
      activation. Although MKK2-EE plants shared enhanced expression of genes encoding
      enzymes of ethylene (ET) and jasmonic acid (JA) synthesis, ET, JA, and salicylic
      acid (SA) levels did not differ dramatically from those of wild-type or mkk2-null
      plants under ambient growth conditions. Upon P. syringae pv. tomato DC3000
      infection, however, MKK2-EE plants showed reduced increases of JA and SA levels.
      These results indicate that MKK2 is involved in regulating hormone levels in
      response to pathogens. MKK2-EE plants were more resistant to infection by P.
      syringae pv. tomato DC3000 and Erwinia carotovora subsp. carotovora, but showed
      enhanced sensitivity to the fungal necrotroph Alternaria brassicicola. Our data
      indicate that MKK2 plays a role in abiotic stress tolerance and plant disease
      resistance.

PMID- 17506337
TI  - Still an abhorrent practice?

PMID- 17506338
TI  - Dishonesty in medical research.

PMID- 17506340
TI  - Witness immunity: dog-eared or defiant?

PMID- 17506339
TI  - Nurse prescribing in practice.

PMID- 17506341
TI  - Methylation of CpG dinucleotides in the promoter region of the gene encoding the
      S100b protein in BALB/cLac mice.

PMID- 17506342
TI  - The role of p14 subunit of replication protein A in binding to single-stranded
      DNA.

PMID- 17506343
TI  - Molecular modeling of the complex between the xWNT8 protein and the CRD domain of
      the mFZD8 receptor.

PMID- 17506344
TI  - The PS II complex possesses a quinone-binding site that differs from Q(A) and
      Q(B) and interacts with cytochrome b559.

PMID- 17506345
TI  - A new broad specificity deoxyribonucleoside monophosphate kinase encoded by gene
      52 of phage phi C31.

PMID- 17506346
TI  - Measurement of the force developed by disassembling microtubule during calcium
      induced depolymerization.

PMID- 17506347
TI  - Mechanical-electrical processes involved in the synchronization of the sinus node
      from atria.

PMID- 17506348
TI  - Modeling and analysis of ligand-receptor interactions in the GABAc receptor.

PMID- 17506349
TI  - Polymorphism of full-length copies of the transposable element MDG4 (gypsy)
      cloned from the Drosophila melanogaster strain G32.

PMID- 17506350
TI  - Analysis of the effect of the polyprenol preparation ropren and the choline
      alphoscerate preparation gliatilin on the membrane-bound and soluble forms of
      cholinesterases and monoamine oxidase of rat brain and serum in the
      tetrachloromethane model system of hepatic encephalopathy.

PMID- 17506351
TI  - Phosphorylation of MAK-V protein kinase in mammalian cells.

PMID- 17506353
TI  - "Microbial inactivation by microwave radiation in the home environment".

PMID- 17506352
TI  - The effect of the structure of the nitrogen-containing heterocycle on reversible
      anticholinesterase effect of heterocyclic thionephosphonates of different
      hydrophobicity.

PMID- 17506354
TI  - Beneficial effects of implementing an announced restaurant inspection program.
AB  - Announced inspections are being incorporated into restaurant inspection programs
      to support active managerial control; however, their effectiveness is unknown.
      The study reported here examined the results of 1314 inspections conducted from
      June 2001 through August 2003 in Minneapolis, Minnesota. Of these, 343 were
      routine inspections that preceded and 157 were routine inspections that followed
      an announced inspection, and 501 were routine inspections of restaurants that did
      not undergo an announced inspection. Significant reductions in frequency of
      citations for critical violations in two food safety categories--(1) the person
      in-charge demonstrates knowledge of foodborne-disease prevention and (2)
      prevention of cross-contamination--were seen in establishments that had undergone
      an announced inspection (relative risk [RR] of 0.7, p = .007, and RR of 0.4, p =
      .001, respectively). The frequency of citation for these critical violations did
      not decline in establishments that did not undergo an announced inspection.
      Announced inspections appear to be effective in supporting active managerial
      control and represent a promising approach to improving food safety in
      restaurants.

PMID- 17506355
TI  - Revisiting a hazardous waste site 25 years later.
AB  - The starting point for this research was a case study of illegal hazardous waste
      disposal published 25 years ago in the Journal of Environmental Health. The site,
      located in rural upstate New York, would eventually be managed under county,
      state, and national remediation programs. For this paper, the authors conducted a
      historical analysis of reports published about the site. They also interviewed
      federal, state, and local officials, as well as nearby residents. Drawing on the
      data obtained in these ways, the paper reviews remedial efforts and community
      involvement. Despite considerable time and resources invested by stakeholders,
      groundwater pollution persists at the site. As responsibility for remediation
      moved through higher levels of government, the character of community involvement
      shifted from proactive to reactive to quiescent. Today, neighboring residents
      perceive health problems and demonstrate feelings of powerlessness. Remedial
      activity has required greater investigation over time, resulting in more
      documents detailing a larger number of parameters with increasing scientific
      sophistication. This approach has boosted understanding of groundwater pollution.
      At the same time, recent remediation has been deprived of useful knowledge that
      could have been provided by greater local participation in decision making.

PMID- 17506356
TI  - Health, safety, and ecological implications of using biobased floor-stripping
      products.
AB  - The main objective of the study reported here was to investigate the ecological,
      health, and safety (EHS) implications of using biobased floor strippers as
      alternatives to solvent-based products such as Johnson Wax Professional (Pro
      Strip). The authors applied a quick EHS-scoring technique developed by the
      Surface Solution Laboratory (SSL) of the Toxics Use Reduction Institute (TURI) to
      some alternative, biobased products that had previously performed as well as or
      close to as well as the currently used product. The quick technique is considered
      an important step in EHS assessment, particularly for toxics use reduction
      planners and advocates who may not have the resources to subject many alternative
      products or processes at once to detailed EHS analysis. Taking this step narrows
      available options to a manageable number. (Technical-performance experiments were
      also conducted, but the results are not discussed or reported in this paper). The
      cost of switching to biobased floor strippers was assessed and compared with the
      cost of using the traditional product, both at full strength and at the dilution
      ratios recommended by the respective manufacturers. The EHS analysis was based on
      a framework consisting of five parameters: volatile organic compounds (VOCs); pH;
      global-warming potential (GWP); ozone depletion potential (ODP); and safety
      scores in areas such as flammability, stability, and special hazards, based on
      ratings from the Hazardous Material Classification System (HMIS) and the National
      Fire Protection Association (NFPA). Total EHS scores were calculated with data
      derived from the material safety data sheets. For most cleaning products
      previously investigated by the TURI SSL, the investigators have demonstrated that
      the five key parameters used in the study reported here can successfully be used
      for quick screening of the EHS impacts of cleaning alternatives. All eight
      biobased, or green, products evaluated in the study had better EHS-screening
      scores than did Pro Strip. One product, Botanic Gold, had a screening score of 49
      out of a possible 50. This score was much higher than the score of 26 achieved by
      Pro Strip. The other biobased floor strippers had EHS-screening scores of > or
      =37, which is the average value of solvent-based cleaning solutions. These
      results indicate that biobased cleaning products capable of floor stripping are
      potentially better than traditional products with respect to the five EHS
      parameters used. The cost of switching to biobased floor strippers at their full
      strength ranged from a minimum of U.S. $15.50 per gallon ($4.10 per liter) for
      Eco Natural Floor Stripper (WPR) to about $59.00 per gallon ($15.61 per liter)
      for Botanic Gold. At 25 percent volume by volume (v/v), the recommended dilution
      ratio for the traditional product, the cost of the Botanic Gold was $14.75 per
      gallon ($3.90 per liter), or about five times more than that of Pro Strip, which
      was $2.48 per gallon ($0.65 per liter). Since these figures do not reflect all of
      the EHS costs, such as disposal and recycling fees, it is likely that use of
      Botanic Gold could be cost-effective in the long run. The authors therefore
      recommend that detailed EHS analysis be conducted on this alternative biobased
      floor stripper. It is also recommended that large field trials be conducted and
      that janitors' or consumers' perceptions be determined. For detailed assessment
      of eco-toxicological properties of the biobased floor strippers, investigations
      of the common additives in the Botanic Gold formulation should be conducted
      through use of databases on the World Wide Web such as Toxnet. Finally, the
      current policies, regulations, and standards that promote biobased products
      should be investigated to determine their strengths and weaknesses. This would
      encourage a broader public debate about the future of the biobased industry in
      the context of sustainability.

PMID- 17506357
TI  - Potential for parasite and bacteria transmission by paper currency in Nigeria.
AB  - The authors assessed the potential of Nigerian currency notes to act as
      environmental vehicles for the transmission of pathogenic parasites and bacteria.
      Currency notes obtained from four major cities in Nigeria were evaluated
      according to standard techniques. Fifty-four (21.6 percent [95 percent CI: 16.50
      26.70]) of the first batch of 250 notes, which underwent parasitological
      analysis, were contaminated with enteric parasites; 133 (53.2 percent [95 percent
      CI: 47.02-59.39]) of the second batch of 250 notes, which underwent
      bacteriological analysis, were found to be contaminated with bacteria. Parasites
      that were isolated from the notes included Ascaris lumbricoides (8.0 percent),
      Enterobius vermicularis (6.8 percent), Trichuris trichiura (2.8 percent), and
      Taenia species (4.0 percent). Bacteria that were isolated were Streptococcus
      species (21.6 percent), Staphylococcus species (12.8 percent), Escherichia coli
      (13.2 percent), and Bacillus species (5.6 percent). Among dirty/mutilated
      currency notes, parasite contamination and bacterial contamination were both
      significantly (p < .05) more pervasive (30.6 percent and 73.8 percent,
      respectively) than they were among clean and mint currency notes. Lower
      denomination notes were more likely to be contaminated than were higher
      denomination notes, although the difference was not statistically significant (p
      > .05). Parasite contamination and bacteria contamination were both most frequent
      in notes obtained from butchers and beggars. These results suggest that currency
      notes may be contaminated, especially with bacteria and enteric parasites, and
      may serve as sources of infection. Personal hygiene to reduce risk of infection
      is recommended.

PMID- 17506358
TI  - "Straight talk about NEHA and policy".

PMID- 17506359
TI  - Occupational hygiene in two combined-drum-and-tunnel composting plants managing
      source separated biowaste and sludge.
AB  - Occupational hygiene was investigated in two Finnish combined-drum-and-tunnel
      composting plants, Plant A (composting sewage sludge) and Plant B (composting
      source-separated biowaste), in 1998-2000. The concentrations of viable mesophilic
      and thermophilic microbes (fungi, bacteria, and actinomycetes), the total number
      of microbes (viable + dead), endotoxin concentrations, and noise level were
      determined for each plant. In addition, dust concentrations were investigated in
      Plant B. In Plant A, working areas were aired before the measurements were taken.
      Differences in microbe concentrations between the plants were statistically
      significant. There were more problems with microbes in Plant B, where the working
      areas were not aired, Also, endotoxins were a problem in Plant B; the threshold
      value of 200 endotoxin units per cubic meter was exceeded in several
      measurements.

PMID- 17506360
TI  - Preparing to receive the Crumbine Award.

PMID- 17506361
TI  - Recreational water illness prevention and swimming pool operation: moving beyond
      the basics.

PMID- 17506362
TI  - The evolution of local environmental health programs.

PMID- 17506363
TI  - Verification of publications, presentations and posters by applicants to a
      residency in obstetrics and gynecology.
AB  - OBJECTIVE: To determine if the publications, presentations and posters reported
      by applicants to the obstetrics and gynecology residency program at Jersey Shore
      University Medical Center could be verified in electronic databases. STUDY
      DESIGN: We conducted a retrospective review of all applications for obstetrics
      and gynecology residency positions at Jersey Shore University Medical Center in
      2006. A systematic search using electronic databases was performed on the
      information reported in the application. RESULTS: There were 111 applicants
      (45%), who reported a total of 490 items. Of these, 119 (24.3%) were confirmed,
      359 (73.3%) could not be confirmed, and 12 (2.4%) were misrepresented.
      CONCLUSION: The majority of publications, presentations and posters reported by
      applicants to the obstetrics and gynecology residency program could not be
      verified in electronic databases.

PMID- 17506364
TI  - Effects of tubal ligation among American women.
AB  - OBJECTIVE: To examine 2 possible negative effects for women who have had a tubal
      ligation using a nationally representative sample. STUDY DESIGN: Our research
      used bivariate statistics to profile women with tubal ligations as compared to
      those without tubal ligations and logistic regression models to examine the
      relationship between having a tubal ligation and 2 measures that indicate sexual
      dissatisfaction. RESULTS: We found that women who have had a tubal ligation are
      more likely than women who have not had a tubal ligation to report (1) stress
      interfering with sex and (2) seeing a physician regarding sexual problems,
      controlling for relevant variables. CONCLUSION: Women, their physicians and the
      public in general should have more detailed information regarding the effects of
      sterilization so that more informed decisions can be made about contraception and
      surgical sterilization procedures.

PMID- 17506365
TI  - Surgical treatment of adnexal masses in pregnancy: indications, surgical approach
      and pregnancy outcome.
AB  - OBJECTIVE: To analyze the indications, surgical approach and pregnancy outcome in
      women undergoing surgical treatment of adnexal masses in pregnancy. STUDY DESIGN:
      In this retrospective study, 51 women were enrolled. Preoperative sonographic
      appearance, the size of the tumor, patient's age, gestational age at the time of
      surgery and pregnancy outcome following a laparoscopic and/or laparotomy approach
      were evaluated. The data were obtained from the National Perinatal Informational
      System, National Cancer Registry, inpatient records, operative reports and
      pathology records, and responses to a questionnaire on pregnancy outcome mailed
      to all the patients. RESULTS: Of the 51 pregnant women with adnexal masses, 27
      were treated laparoscopically and 24 through laparotomy. Acute symptoms were the
      indication in 14 (27.4%) and tumor > 5 cm or sonographic appearance in 37
      (72.6%). There were 44 (86.4%) benign and 7 (13.6%) malignant masses (4
      borderline and 3 cancers). There were no differences in pregnancy outcome between
      emergency and planned surgery or between laparoscopy and laparotomy. CONCLUSION:
      Surgical treatment of persistent adnexal masses in pregnancy, particularly those
      with a sonographic appearance of a complex tumor, is justified because of the
      high risk of torsion, rupture and malignancy. Immediate treatment of symptomatic
      masses permits conservative, fertility-preserving surgery and has no adverse
      effect on pregnancy outcome. Laparoscopic surgery and surgery in the first
      trimester do not impair pregnancy outcome.

PMID- 17506366
TI  - Use of progesterone to prevent preterm birth at a tertiary care center.
AB  - OBJECTIVE: To assess the prescription patterns of progesterone for the prevention
      of preterm birth in a tertiary center. STUDY DESIGN: We examined electronic
      medical records for all women receiving care in the high risk obstetric clinics
      at a tertiary care center from July 2003 to June 2004. Demographic information,
      progesterone offers, progesterone therapy accepted and received, and barriers to
      receiving progesterone were collected. Women were placed into 1 of 4 categories:
      appropriate offer, appropriate nonoffer, inappropriate offer and inappropriate
      nonoffer. RESULTS: Five hundred two patients sought prenatal care in the clinics
      during the study period. Of 143 women with a prior preterm birth, 60 (42%) were
      considered to be candidates for progesterone. Of these, 34 of 60 (57%) were
      offered progesterone therapy (appropriate offer). Of the 442 women who were not
      appropriate progesterone candidates, 9 (2%) were offered progesterone
      (inappropriate offer). CONCLUSION: Our data suggest that a substantial proportion
      of eligible women are not being offered progesterone for the prevention of
      preterm birth. More data are needed regarding barriers to progesterone use and
      what programs may best influence physicians to use progesterone appropriately.

PMID- 17506367
TI  - Postoperative femoral motor neuropathy: diagnosis and treatment without
      neurologic consultation or testing.
AB  - OBJECTIVE: To review the diagnosis and treatment of postoperative femoral motor
      neuropathy without neurologic consultation or testing. STUDY DESIGN: A
      retrospective review of 6 consecutive patients with postoperative femoral motor
      neuropathy following gynecologic surgery. Diagnosis was made on clinical
      evaluation: history of falling during postoperative ambulation, quadriceps
      weakness, straight leg raise weakness, diminished knee jerk response, and no
      evidence of psoas hematoma or abscess. Neurologic consultation, electromyography,
      nerve conduction study and radiologic imaging, such as computed tomography, were
      not obtained. Instead, a physical therapy consultation was obtained for a knee
      orthotic and rehabilitation. RESULTS: Four postoperative femoral motor
      neuropathies developed following 3,014 cases of major gynecologic surgery (0.1%).
      Two additional cases were seen in consultation. The median age was 57 years. All
      patients fell while attempting ambulation on postoperative day 1. Recovery
      occurred at a median of 3 months (1-4). At a median follow-up of 4 years, no
      patient had developed additional neurologic sequelae. A history of prior
      postoperative femoral motor neuropathy was noted in 2 of 6 patients (33%).
      CONCLUSION: This was the first study of diagnosis and treatment of postoperative
      femoral motor neuropathy following gynecologic surgery without neurologic
      consultation or testing. Because of the significant expense of neurologic
      consultation and testing, patients with postoperative femoral motor neuropathy
      can have the condition diagnosed by the gynecologist and be referred directly to
      physical therapy without adversely affecting outcome. This also was the first
      study to elicit a prior history offemoral neuropathy in 33% of patients. Thus, a
      prior history may be a risk factor for recurrence.

PMID- 17506368
TI  - Pregnancy outcome after stillbirth.
AB  - OBJECTIVE: To assess the subsequent pregnancy outcome in women with previous
      stillbirth. STUDY DESIGN: The study included all women (n = 54) who delivered a
      stillbirth between 1997 and 2001 in our department. A control group of women with
      live birth (n = 108) was matched for delivery within the same year, maternal age
      (+/- 3 years), parity (+/- 1) and gestational age at delivery (+/- 2 weeks). On
      February 1, 2004, the charts of these women were examined for subsequent
      pregnancies. RESULTS: Similar subsequent pregnancy rates were found in women with
      previous stillbirth and live birth (61.1% and 54.6%), respectively. There were no
      recurrences of stillbirth; gestational age at delivery, birth weight and Apgar
      score at 5 minutes were similar to those in the control group, and there was no
      statistically significant increase in abortion, induction or cesarean section
      rates. CONCLUSION: There is a favorable outcome in pregnancy following
      stillbirth. This information is useful for prepregnancy counseling of parents
      with previous stillbirth.

PMID- 17506369
TI  - Amniotic fluid index as a predictor of adverse perinatal outcome in the HELLP
      syndrome.
AB  - OBJECTIVE: To evaluate the prognostic value of an amniotic fluid index (AFI) < or
      = 5 cm for an adverse perinatal outcome in pregnancies with the syndrome of
      hemolysis, elevated liver enzymes and low platelets (HELLP syndrome). STUDY
      DESIGN: A prospective, observational study of patients with the HELLP syndrome.
      An ultrasound estimate of amniotic fluid volume was obtained on admission.
      Adverse intrapartum outcomes included amnioinfusion for variable decelerations
      and/or indicated abdominal/vaginal operative delivery for nonreassuring fetal
      heart rate changes. Maternal characteristics and perinatal outcome parameters
      were compared AFI < or = vs. > 5 cm. Statistical analysis was performed using
      chi2 analysis, Student's t test and receiver-operator characteristic curve (ROC)
      analysis. RESULTS: Between January 1996 and February 1999, 120 patients were
      enrolled. Twenty-six (22%) had an AFI < or = 5 cm. This group did not differ from
      that with AFI > 5 cm regarding the severity of the HELLP syndrome, admission-to
      delivery interval (p = 0.354), variable decelerations in labor (p = 0.06), Apgar
      score of < 7 at 5 minutes (p = 0.361), cesarean delivery for nonreassuring fetal
      status (p = 1.0) or significant fetal acidosis (pH < 7.0 [p = 0.2101). ROC
      analysis revealed no AFI measurement between 0 and 16 cm that was useful for
      identifying the compromised fetus. CONCLUSION: Antepartum/intrapartum performance
      of AFI in patients with the HELLP syndrome is a poor prognostic test for
      subsequent fetal compromise.

PMID- 17506370
TI  - Gestational diabetes: fasting and postprandial glucose as first prenatal
      screening tests in a high-risk population.
AB  - OBJECTIVE: To evaluate the value of fasting (FPG) and 2-hour postprandial (PPG)
      plasma glucose as screening tests for gestational diabetes mellitus (GDM) in a
      high-risk population during early pregnancy. STUDY DESIGN: At their first
      prenatal visit, 708 women underwent FPG and PPG for universal screening for GDM,
      with the diagnosis confirmed by the 75-g oral glucose tolerance test (World
      Health Organization criteria). The area under the receiver operating
      characteristic curve (AUC) was used to analyze the performance of the 2 screening
      tests. RESULTS: Of 184 (25.9%) women with GDM, 79 (42.9%) were identified before
      18 weeks. The AUC for FPG to predict GDM was 0.579 (95% CI 0.531-0.627). Though a
      threshold of 85 mg/dL achieved minimally acceptable sensitivity, 79.9%, the
      corresponding specificity remained poor, 27.5%, with a false positive rate (FPR)
      of 72.5%. The AUC for PPG was 0.717 (95% CI 0.670-0.765); a cutoff of 95 mg/dL
      achieved a sensitivity of 79.9% and FPR of 53.1%. CONCLUSION: Though GDM could be
      diagnosed in > 40% women in early pregnancy at their first prenatal visit, the
      poor specificity and high FPR of FPG and PPG, alone or in combination, make them
      unsuitable screening tests for GDM.

PMID- 17506371
TI  - Local activation of TGF-beta1 at endometriosis sites.
AB  - OBJECTIVE: To investigate the factors related to activation of transforming
      growth factor-beta 1 (TGF-beta1) at sites of endometriosis. STUDY DESIGN: TGF
      beta1 is activated by plasmin, which is formed when plasminogen is activated by
      urokinase-type plasminogen activator (uPA). We studied these factors by
      immunohistochemistry or immunoassay. RESULTS: TGF-beta1 protein was localized
      mainly in the cytoplasm of glandular epithelial cells in both endometriotic cysts
      and normal endometrium, but strongly positive immunostaining was significantly
      more common in cysts. The levels of TGF-beta1, uPA and plasmin/alpha2-plasmin
      inhibitor complex were all higher in cyst fluid than in peritoneal fluid. There
      was little uPA protein expression in the glandular epithelium of normal
      endometrium, but it was prominent in the cytoplasm of glandular epithelial cells
      from endometriotic cysts, and strongly positive immunostaining was significantly
      more common in cysts. CONCLUSION: These results suggest that TGF-beta1 activity
      is increased at sites of endometriosis due to enhanced production of both uPA and
      TGF-beta1 by glandular epithelium and because plasmin activates TGF-beta1 after
      being converted from plasminogen by uPA.

PMID- 17506372
TI  - Role of placental growth hormone in the alteration of maternal arterial
      resistance in pregnancy.
AB  - OBJECTIVE: To investigate the relation between arterial resistance and placental
      growth hormone (hGH-V) levels in the maternal circulation. STUDY DESIGN: Sixty
      seven women with normal pregnancy, 13 with preeclampsia (PE) and 11 with
      intrauterine fetal growth restriction (IUGR) underwent Doppler sonography of the
      placental and nonplacental uterine and cubital artery and blood sampling. hGH-V
      was measured with a highly sensitive sandwich-type immunofluorometric assay and
      pituitary growth hormone (hGH-N) and insulinlike growth factor I (IGF-I) with a
      chemiluminescence assay. A p value of < 0.05 was considered significant. RESULTS:
      During normal pregnancy the arterial pulsatility index (PI) decreased (p <
      0.001), serum levels of hGH-V and IGF-I increased (p < 0.0001), and hGH-N
      decreased (p < 0.0001). Pathologic pregnancies (PE, IUGR) showed a significant
      higher PI in all arteries, but hGH-V and the IGF-I were decreased. CONCLUSION:
      Our data demonstrate a strong correlation between decreasing uterine and
      peripheral arterial resistance and increasing hGH-V during normal pregnancies
      with impaired uterine blood flow there were lowered serum levels of hGH-V, hGH-N
      and IGF-I. Lower levels of hGH-V and hGH-N might contribute to impaired
      uteroplacental circulation.

PMID- 17506373
TI  - Congenital cytomegalovirus infection in 1 twin with a pericardial effusion: a
      case report.
AB  - BACKGROUND: Congenital fetal damage related to cytomegalovirus (CMV) infection is
      largely attributable to maternal primary infection. Twin fetuses may react
      differently to the same maternal influences. CASE: A woman had a sonographically
      documented fetal pericardial effusion in 1 twin at 33 weeks of gestation. The
      workup for maternal infection and fetal structural anomaly was negative except
      for positive CMV Ige in the maternal serum Cesarean section was performed due to
      fetal distress. After delivery, CMV viral antigenemia was found in 1 twin with
      petechiae, thrombocytopenia, hepatosplenomegaly and ventriculomegaly. The other
      twin was not infected and in stable condition. CONCLUSION: Since twin fetuses
      simultaneously exposed to the same maternal influence had a completely different
      outcome, maternal factors play a limited role in influencing CMV transmission.

PMID- 17506374
TI  - Ovarian pregnancy without definitive pathologic confirmation: a case report.
AB  - BACKGROUND: Ovarian pregnancy is one of the rarest forms of ectopic pregnancy.
      Diagnosis is based on criteria established in 1878 by Spiegelberg; they require
      specific pathologic characteristics in order to formally confirm an ovarian
      pregnancy. CASE: A woman presented with a clinical picture of ectopic pregnancy
      that, upon exploration, seemed to be ovarian. Although the pathologic picture did
      not meet the exact definition of ovarian pregnancy, the final pathology and
      clinical follow-up could not be explained by any other diagnosis. CONCLUSION:
      Considering our experience and other reported cases, we think that the
      Spiegelberg criteria for the diagnosis of ovarian pregnancy require
      reconsideration and perhaps modification.

PMID- 17506375
TI  - Group B streptococcus toxic shock-like syndrome in a healthy woman: a case
      report.
AB  - BACKGROUND: Toxic shock syndrome (TSS) is caused by Staphylococcus aureus
      infection. The disease entity manifests clinically as fever, hypotension, diffuse
      macular erythema that progresses to desquamation, and dysfunction of > 3 organ
      systems. Toxic shock-like syndrome (TSLS) has the same clinical manifestation as
      TSS but is caused by Streptococcus, usually group A, C or G. Here we report on a
      healthy woman who experienced group B Streptococcus (GBS)-related TSLS, possibly
      related to tampon use. CASE: A 37-year-old woman, gravida 1, para 1, met the
      diagnostic criteria for TSS/TSLS 5 days after her last tampon use. Blood, urine
      and vaginal cultures were positive only for GBS. Analysis of the blood isolate
      suggested a novel GBS superantigen. CONCLUSION: This is the second reported case
      of GBS causing tampon-associated TSS/TSLS. Up to 40% of healthy menstruating
      women are vaginally colonized with GBS. Superantigens elaborated by staphylococci
      and streptococci induce an immunologic mediator storm that affects the
      circulatory and end-organ systems to produce the clinical picture. Prompt medical
      therapy involves large-volume isotonic fluid resuscitation and antibiotic
      coverage with vancomycin and an antistaphylococcal beta-lactam. Clindamycin may
      dampen the immunologic response and endotoxin production. Corticosteroids and
      intravenous immunoglobulin may be useful adjuncts; however, nonsteroidal
      antiinflammatories should be avoided.

PMID- 17506376
TI  - Adenosarcoma of an endometrial polyp in a 27-year-old nulligravida: a case
      report.
AB  - BACKGROUND: Endometrial adenosarcoma is a rare tumor first described by Clement
      and Scully in 1974. It consists of benign or atypical neoplastic glands within a
      sarcomatous stroma and represents approximately 8% of all uterine sarcomas.
      Patients of a variety of ages are affected: the largest series reported 100 cases
      in patients aged 14-89 years, with the median age at presentation 58 years. Other
      case reports identified on a literature search also describe patients within this
      age range. The typical presentation is symptoms of abnormal vaginal bleeding. On
      examination, tissue protruding from the external cervical os is a common finding,
      with a smaller number of patients having an enlarged uterus or palpable pelvic
      mass. The standard management is total abdominal hysterectomy and bilateral
      salpingo-oophorectomy. However, difficulty arises when one is faced with this
      condition in a young nullipara wishing to preserve her fertility. CASE:
      Endometrial polyp adenosarcoma occurred in a 27-year-old, nulligravid woman who
      presented with intermenstrual and postcoital bleeding. She was managed
      conservatively but will require close followup subsequently. CONCLUSION: A
      clinical dilemma was encountered in the management of a young woman with
      endometrial polyp adenosarcoma because of the necessity to preserve her
      fertility.

PMID- 17506377
TI  - Topical immunosuppressants, genital lichen sclerosus and the risk of squamous
      cell carcinoma: a case report.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) has a recognized association with
      lichen sclerosus (LS) of the vulva. Several recent reports have indicated the
      usefulness of the new macrolide immunosuppressant agents pimecrolimus and
      tacrolimus in the treatment of LS, emphasizing the advantage over topical
      corticosteroids of lack of atophogenicity. Despite this there may be risks
      involved that could outweigh this benefit. The potential of these medications to
      potentiate the risk of SCC in LS in the short and long-term is unknown. Once
      lichen sclerosus is well controlled, there is often no need for ongoing use of
      superpotent corticosteroids, and there may be no reason to use immunosuppressants
      when moderate-strength corticosteroids provide adequate control. CASE: A 73-year
      old woman with a 10-year history of hypertrophic LS and genital psoriasis
      presented with intractable superimposed inflammatory vulvitis. She was treated
      with topical pimecrolimus 1% cream on the assumption that she was either allergic
      to or intolerant of topical corticosteroids. One month after commencing therapy,
      she suddenly developed a rapidly growing vulvar tumor. This was excised and
      proved to be a well-differentiated squamous cell carcinoma. CONCLUSION: It may be
      safest to restrict the use of topical immunosuppressives to patients with LS who
      are unable to use topical corticosteroids because of the risk of potentiating
      SCC.

PMID- 17506378
TI  - Successful rescue of an early interstitial pregnancy after failed systemic
      methotrexate treatment: a case report.
AB  - BACKGROUND: Interstitial (cornual) pregnancy is a rare and life-threatening
      disease. Although systemic treatment with methotrexate (MTX) in an unruptured
      interstitial pregnancy has been used to preserve the entirety of the uterus,
      surgery is often used as a rescue method in failed cases. Use of an ultrasound
      guided local injection can be a good alternative to surgery. CASE: A 30-year-old
      woman, gravida 1, para 0, with an interstitial pregnancy at 10 weeks of
      gestation, was successfully treated with an ultrasound-guided 100-mg MTX
      injection after a failed response to 3-dose intramuscular 100-mg MTX treatment
      (300 mg in total). Regular menstruation occurred 1 month after the local MTX
      injection. The serum beta-human chorionic gonadotropin level was undetectable 49
      days later, and the residual mass had disappeared 6 months later, CONCLUSION:
      Local injection of MTX may be a good means of managing an unruptured interstitial
      pregnancy to preserve the entirety of the uterus after failed systemic MTX
      treatment. Use of a local MTX injection may be a better choice than that of
      systemic MTX treatment.

PMID- 17506379
TI  - Pregnancy complicated by asymptomatic uterine arteriovenous malformation: a case
      report.
AB  - BACKGROUND: Uterine arteriovenous malformation (AVM) is a rare disease.
      Percutaneous arterial embolization has been performed for patients who wish to
      preserve their ability to conceive. CASE: A 27-year-old primigravida was admitted
      for treatment of threatened premature labor at 21 weeks of gestation. She had
      been diagnosed with asymptomatic uterine AVM 2 years previously. She had not
      received any treatment before conception. At 41 weeks of gestation she
      spontaneously delivered a healthy infant weighting 3,154 g. and the Excessive
      bleeding (1,600 mL) occurred, probably due to eruption of the AVM vessel at the
      time of parturition. At 3 months postpartum, the patient underwent arterial
      embolization of AVM. CONCLUSION: The management of uterine AVM should be
      individualized, taking into account the patient's desire to maintain her
      fertility and the symptoms.

PMID- 17506380
TI  - Simultaneous cesarean section and radical nephrectomy for angiomyolipoma with
      spontaneous bleeding during pregnancy: a case report.
AB  - BACKGROUND: Renal angiomyolipoma with spontaneous bleeding during pregnancy is an
      extremely rare condition and may jeopardize both the mother and fetus. The ethics
      of reproductive medicine, method of diagnosis, option for management and optimal
      time for surgical intervention can be arguable in this situation. CASE: A 31-year
      old woman presented with dull right flank pain at 12 weeks' gestation. Abdominal
      sonography and renal magnetic resonance imaging revealed a hypervascular and fat
      containing mass with mother and fetus bleeding at the right kidney. Due to stable
      hemodynamic status, the patient was treated conservatively and underwent
      elective, simultaneous cesarean section and radical nephrectomy safely at 38
      weeks' gestation. Angiomyolipoma of the right kidney was diagnosed on pathologic
      examination. CONCLUSION: Renal angiomyolipoma with spontaneous bleeding during
      pregnancy is a dangerous condition that may cause mortality in the mother and
      fetus, but elective, simultaneous cesarean section and radical nephrectomy can be
      performed safely if the hemodynamic status is stable.

PMID- 17506381
TI  - Vaginal schwannoma: a case report.
AB  - BACKGROUND: Schwannomas (peripheral nerve sheath tumors) of the female genital
      tract are extremely rare. CASE: A 31-year-old woman developed a benign schwannoma
      involving the anterior vaginal wall. CONCLUSION: Schwannomas of the female
      genital tract are extremely rare. They are generally benign, and simple excision
      is adequate treatment.

PMID- 17506382
TI  - Correlations between maternal periodontal conditions and preterm low birth weight
      infants.
AB  - OBJECTIVE: The goal of this cross-sectional study was to assess the correlation
      between periodontal conditions of pregnant women and characteristics of the
      infant at birth. METHODS: One hundred thirteen pregnant patients received a
      thorough dental and periodontal examination and questionnaire. Probing depth
      (PD), clinical attachment level (CAL), bleeding on probing (BOP), and calculus
      index (CI) were recorded. Patients were classified as to whether they had
      periodontitis (presence of 2 or more teeth with 1 or more sites experiencing CAL
      > or = 3 mm and PD > or = 4 mm at the same site), gingivitis (> or = 25% of sites
      with BOP), or healthy periodontium. Patients were followed to ascertain
      information on pregnancy-related complications, gestational age, and birth
      weight. Miscarriages and infants born as single births at < 37 weeks or weighing
      < 5.5 pounds were classified as preterm low birth weight (PT/LBW) infants. The
      periodontal clinical parameters were compared between groups using the Kruskal
      Wallis test and the Wilcoxon rank sum test. Spearman rank correlation
      coefficients were calculated to estimate the correlations. RESULTS: Of the 113
      pregnant patients, outcome data were available on 111 patients. In addition, data
      from one patient who delivered twins and two patients who had miscarriages were
      not considered in the correlation analyses. The prevalence of periodontitis and
      gingivitis in this population was 23.9% and 54%, while the prevalence of PT/LBW
      infants was 19%, 7%, and 13% among the patients with periodontitis, gingivitis,
      and healthy periodontium, respectively. Given the small number of patients with
      PT/LBW infants, we were unable to identify any statistically significant
      associations between the periodontal clinical parameters and PT/LBW, although the
      data suggested the trend that patients with PT/LBW infants were more likely to
      have poorer probing depths (median number of sites with PD > or = 4mm, 13 vs. 6;
      p = 0.19). Among the 108 single births, birth weight was negatively correlated
      with maternal mean PD in the periodontitis group (r = -0.37, p = 0.055), and the
      percentage of sites with BOP in the mandible (r = -0.32, p = 0.014), total CL (r
      = -0.31, p = 0.01 7) and maxillary arch CI (r = -0.29, p = 0.025) in the
      gingivitis group. CONCLUSION: Infant birth weight showed moderate relationships
      with maternal periodontal conditions in subjects with periodontal diseases.

PMID- 17506383
TI  - Gingival hyperplasia in hyaline fibromatosis--a report of two cases.
AB  - Hyaline fibromatosis is a rare inherited autosomal recessive disorder affecting
      connective tissue, characterized by an accumulation of hyaline material in the
      skin and other organs. This paper reports the oral findings of two cases of
      hyaline fibromatosis referred to our dental clinic due to extensive overgrowth of
      gingival tissue in the oral cavity that affected their eating and breathing. One
      patient was diagnosed with infantile systemic hyalinosis while the other was
      diagnosed with juvenile hyaline fibromatosis. Both cases showed similar clinical
      and histopathological findings, but one patient exhibited a more severe form of
      the disease, therefore it is difficult not to consider them as part of the same
      disorder. Children with such conditions have special dental needs, thus early
      dental consultation is important to begin caries prevention measures and dental
      therapy. No known therapy exists for hyaline fibromatosis. Currently, the only
      treatment is surgical excision of the lesions to improve esthetics and function.

PMID- 17506384
TI  - The influence of a gummy smile on lip seal.
AB  - OBJECTIVE: The purpose of this study was to verify the influence of excessive
      gingival display on lip seal. METHODS: Eighteen individuals with gummy smiles and
      poor lip seal were submitted to orofacial myofunctional assessment and surface
      electromyography in order to verify the action potential amplitude of mentalis
      muscle action generated during muscular exertion. Periodontal surgery was
      performed to remove excessive gingival tissue and bone volume from the pre
      maxilla, and after 6 months, the patients were re-evaluated. RESULTS: Decreased
      contraction and tensing of the mentalis muscle (chin dimpling) was clinically
      observed when attempting lip seal and electromyographical analysis revealed a
      statistically significant difference among action potential values during
      muscular exertion to achieve lip contact. CONCLUSION: It was concluded that lip
      seal is influenced by gingival bone volume and that surgical removal contributed
      to a smoother contact between the lips.

PMID- 17506385
TI  - Clinical attachment level measurements with and without the use of a stent by a
      computerized electronic probe.
AB  - OBJECTIVE: The aim of the present study was to evaluate whether a stent should be
      used when assessing attachment level (AL) by an electronic probe (Florida Probe).
      METHODS: Twenty patients were recruited and individual stents were obtained to
      measure relative AL (RAL) with the Florida stent probe. Conventional AL (CAL)
      measurements were obtained by adding pocket depth and gingival recession recorded
      by the Florida pocket probe. Duplicate RAL and CAL measurements were taken one
      hour apart from each other on anterior teeth, at six sites per tooth, by one
      examiner. Patients were treated and reassessed with both probes after 45 days so
      that the gain in RAL and CAL could also be compared. RESULTS: Pearson's
      correlation test showed that correlation was moderate (r = 0.57) and significant
      (p < 0.001) for duplicate CAL measurements. As for RAL values, correlation was
      higher (0.91) and significant (p < 0.001). The difference between RAL and CAL
      gain after 45 days was 0.04 mm (p = 0.85). CONCLUSION: Since the correlation was
      higher for duplicate RAL measurements than for CAL measurements, the use of a
      stent should be considered in clinical trials to ensure better reproducibility of
      measurement of attachment level gains.

PMID- 17506386
TI  - Dental and periodontal alterations in Berardinelli-Seip syndrome.
AB  - BACKGROUND: Congenital generalized lipodystrophy (CGL), or Berardinelli-Seip
      congenital lipodystrophy (BSCL), is a rare disorder characterized by the absence
      of body fat and resistance to insulin. Other manifestations, such as acanthosis
      nigricans, hepatomegaly, hyperandrogenism, muscular hypertrophy, and diabetes
      mellitus may be seen. Although the general clinical picture of this disease has
      already been characterized, there has yet been no description of the dental
      manifestations of individuals with this disease. METHODS: Eight patients with
      BSCL were assessed (4 adults and 4 children/adolescents), with ages ranging
      between 4 and 35 years, of which 6 had diabetes mellitus. Gingival bleeding index
      (GBI) was measured and periodontal probing, caries detection and visual
      examination of gingival volume were performed. RESULTS: GBI was variable and was
      related to poor oral hygiene. There was a marked presence of caries and no
      alteration in gum tissue growth was observed. Important anomalies were detected
      in the periodontal examination. The patients over the age of 30 years had an
      aggressive and generalized form of periodontal disease, uncommon for this age.
      The etiology of these alterations may be the diabetes mellitus present in these
      patients since childhood. CONCLUSION: We concluded that a predisposition to
      caries must be reviewed and periodontal disease must be systematically
      investigated in individuals with BSCL, since periodontitis may be seen along with
      the numerous systemic complications.

PMID- 17506387
TI  - [Hypercholesterolemia and control with therapy].

PMID- 17506388
TI  - [Effect of ultra-endurance swimming on body composition--marathon swim 2006 from
      Rapperswil to Zurich].
AB  - We measured, during a marathon swimming event 2006 in the lake of Zurich, load
      intensity, energy intake, energy expenditure and impact on both muscle and fat
      mass in a trained long-distance swimmer. The swimmer had a load intensity of 125
      bpm corresponding to 51% VO2(max). Despite adequate energy intake during the
      load, an energy deficit of 500 kcal per hour occurred, which resulted in a loss
      of 1.1 kg body mass within 9 hours of swimming.

PMID- 17506389
TI  - [Back pain and acne conglobata: SAPHO syndrome].
AB  - We report on a young woman suffering from SAPHO syndrome with back pain and
      arthritis of the sternoclavicular joints. This inflammatory disorder of the
      osteoarticular system (synovitis, osteitis, and hyperostosis) is associated with
      severe acne or palmoplantar pustulosis. The patient was treated with pamidronate,
      NSAID and physiotherapy which improved the musculoskeletal symptoms completely.
      The acne was treated with isotretinoin.

PMID- 17506390
TI  - [Hemorrhage in vitamin K deficiency--a preventable entity].

PMID- 17506391
TI  - [Young patient with dementia].

PMID- 17506393
TI  - MDA building project stalls.

PMID- 17506392
TI  - [Narrow and broad complex tachycardia].

PMID- 17506394
TI  - Editorial clarification sought.

PMID- 17506395
TI  - Patient fact sheet. Diabetes and your oral health.

PMID- 17506396
TI  - Let's send the right message.

PMID- 17506397
TI  - Reporting requirements for child or adult abuse.

PMID- 17506398
TI  - Promotion from within: a good idea?

PMID- 17506399
TI  - Volunteerism and the young dentist.

PMID- 17506400
TI  - How to save big bucks in your practice: Part II.

PMID- 17506401
TI  - From stunned to stunning....

PMID- 17506402
TI  - University of Detroit Mercy School of Dentistry: 75 years of excellence.

PMID- 17506403
TI  - UDM's new campus: a closer look.

PMID- 17506404
TI  - UDM Dean Steiman: Out of adversity comes opportunity.

PMID- 17506405
TI  - Dental premedication protocols for patients with knee and hip protheses.
AB  - In 1997, the American Dental Association (ADA) and the American Academy of
      Orthopaedic Surgeons (AAOS) published an advisory statement regarding antibiotic
      prophylaxis for patients with total joint replacements undergoing dental
      treatment. The first periodic update of these guidelines was published in 2003.
      Nevertheless, confusion exists among dentists and physicians as to the clinical
      indications for premedication in this patient population. This article serves as
      an overview of current recommendations for use of chemoprophylaxis in the dental
      treatment of patients ith prosthetic joints.

PMID- 17506406
TI  - Automating infection surveillance efforts. Accurate outbreak data can cut costs,
      antibiotics use.
AB  - A recent survey of 150 infection control specialists concluded that automated
      surveillance systems (computer or Web-based programs that track patient
      infections) can protect patients from hospital-acquired diseases. However, the
      same survey also found that only about 13 percent of the respondents use the
      technology, according to Premier, the GPO that sponsored the survey. Dan
      Peterson, M.D., Premier's vice president and medical director, discusses this
      apparent contradiction and offers advice on how infection control departments can
      justify the hundreds of thousands of dollars required for an automated
      surveillance system.

PMID- 17506407
TI  - Six Sigma plan delivers stellar results.

PMID- 17506408
TI  - Spend pennies to save dollars on instrument repair.

PMID- 17506409
TI  - Involvement and awareness help prevent needlesticks.

PMID- 17506410
TI  - Sterilization cues for containers.
AB  - Questions often arise regarding safe practices relevant to sterilization
      containers-from cleaning these holding devices to the maximum weight for
      containerized instrument sets to shelf life and sterility maintenance. Following
      nationally established, recommended practices can help ensure optimal container
      effectiveness, infection control and patient safety. This month's column
      addresses these subjects and related issues.

PMID- 17506411
TI  - Mobile supply chain improves processes.

PMID- 17506412
TI  - Stats. Who is managing emergency department supplies? Analysis uncovers materials
      and ED staff roles.

PMID- 17506413
TI  - Better maintenance of rolling stock affects infection control, bottom line.

PMID- 17506414
TI  - Low technology systems for wastewater treatment: perspectives.
AB  - Low technology systems for the treatment of wastewater are sometimes presented as
      remnants of the past, nowadays supposedly only meant to serve developing
      countries and remote rural areas. However, considering their advantages and
      disadvantages together with enhanced treatment requirements and recent research
      and technological developments, the future of these systems still appears
      promising. Successful applications of low technology systems require that more
      care is taken of their design and operation than often observed. Correlatively,
      more efforts should be made to decipher the treatment mechanisms and determine
      the related reaction parameters, so as to provide more deterministic approaches
      of the natural wastewater treatment systems and better predict their performance.

PMID- 17506415
TI  - Membrane technology revolutionizes water treatment.
AB  - Membranes play a crucial role in living cells, plants and animals. They not only
      serve as barriers between the inside and outside world of cells and organs. More
      importantly, they are means of selective transport of materials and host for
      biochemical conversion. Natural membrane systems have demonstrated efficiency and
      reliability for millions of years and it is remarkable that most of these systems
      are small, efficient and highly reliable even under rapidly changing ambient
      conditions. Thus, it appears to be advisable for technology developers to keep a
      close eye on Mother Nature. By doing so it is most likely that ideas for novel
      technical solutions are born. Following the concept of natural systems it is
      hypothesized that the Millennium Development Goals can be best met when counting
      on small water and wastewater treatment systems. The core of such systems could
      be membranes in which chemical reactions are integrated allowing recovery and
      direct utilization of valuable substances.

PMID- 17506416
TI  - Biological risks to food crops fertilized with Ecosan sludge.
AB  - This paper presents the microbial effects of using Ecosan sludge in agriculture.
      Sludge from KwaZulu Natal in South Africa having a helminth ova content of around
      30 HO/gTS, faecal coliforms of 10(6) CFU/gTS, faecal streptococi of 10(6) CFU/gTS
      and Salmonella spp. of 10(5) CFU/gTS were applied to soils to grow carrots and
      spinach at different rates. Results showed that helminth ova content in crops was
      always greater in leaves than in stems, with a content varying from 2 to 15
      HO/gTS for spinach and sludge application rates of sludge of 0-37.5 ton/ha and
      from 2-8 HO/gTS in carrots crops for sludge application rates varying from 0 to35
      ton/ha. Health risks resulting from crop consumption were calculated using the
      beta-poisson and the single-hit exponential models for Salmonella and helminths
      eggs, respectively. For Salmonella, no risks were found when consuming carrots
      for all the sludge rates studied while for spinach, risks were high but results
      were not deemed conclusive due to the technical methods used to measure bacteria.
      Concerning helminths, it was found that the morbidity rate will increase by 9%
      for the higher sludge application rates. To increase regional risks by 1% the egg
      content in crops needs to be less than 0.2 HO/gTS.

PMID- 17506417
TI  - Performance of very small wastewater treatment plants with pronounced load
      variations.
AB  - The operation of very small biological wastewater systems is strongly influenced
      by the patterns of wastewater generation. The absence of people in the connected
      building(s) during holidays or off-season leads to a system underload, other
      circumstances however may lead to an overload. Experiments have been carried out
      to display the effects of no-feed conditions on activated sludge biomass and its
      microbial activity during a 24 hour period after re-feeding. The decrease of the
      biomass during idle periods can be modelled by a first order equation. The
      initial specific oxygen uptake rate (OUR) of the remaining biomass decreased with
      the duration of the preceding no-feed sequence. Four different laboratory-scale
      treatment plants were operated to demonstrate the system performance when re
      started after a break period of 24 and 52 days respectively. The effluent
      concentration after a break of 52 days had not been sufficient as compared to the
      discharge requirements given by German laws. In addition a full scale trickling
      filter was monitored, while the connected building accommodated a maximum of 40
      guests interrupted by times with no guest at all. Conclusions are drawn from the
      experimental results and from literature, giving some hints on how to manage the
      impacts of varying loads at very small wastewater treatment plants.

PMID- 17506418
TI  - Treatment of lower load graywater by using a controlled soil natural treatment
      system.
AB  - Experiences of treating graywater by soil natural treatment systems have not been
      widely reported. In general terms, graywater has a lower concentrations of
      organic matter; nutrients (e.g. nitrogen), and microorganisms than combined
      wastewater; therefore, the graywater treatment capacity of soil should be
      evaluated. In this study, the performance of a natural soil treatment system was
      evaluated when shower graywater from a house located at Sapporo City, Japan, was
      treated by a layer of 30 cm of soil from the Hokkaido University Campus. Results
      showed very high removal efficiencies of chemical oxygen demand (98%) and
      Kjeldahl nitrogen (95%) at high infiltration rates (214 cm/d), which denotes that
      natural soil treatment systems could be a good alternative to treat lower load
      graywater.

PMID- 17506419
TI  - Evaluation of an optimal fill strategy to biodegrade inhibitory wastewater using
      an industrial prototype discontinuous reactor.
AB  - This work presents the results and discussions of the application of an optimally
      controlled influent flow rate strategy to biodegrade, in a discontinuous reactor,
      a synthetic wastewater constituted by 4-chlorophenol. An aerobic automated
      discontinuous reactor system of 1.3 m3, with a useful volume of 0.75 m3 and an
      exchange volume of 60% was used. As part of the control strategy influent is fed
      into the reactor in such a way as to obtain the maximal degradation rate avoiding
      inhibition of microorganisms. Such an optimal strategy was able to manage
      increments of 4-chlorophenol concentrations in the influent between 250 and 1000
      mg/L. it was shown that the optimally controlled influent flow rate strategy
      brings savings in reaction time and flexibility in treating high concentrations
      of an influent with toxic characteristics.

PMID- 17506420
TI  - Characterization of the activated sludge and of the operating conditions of six
      SBR treating dairy effluent and operated at industrial scale.
AB  - The sludge from six SBRs treating dairy effluent and located at same geographical
      location, in North East of France, were collected to study their characteristic
      behavior. The six plants were designed and constructed by the same manufacturer
      and are working under quite similar operating conditions. The objective of the
      study was to observe if any similarity existed in the characteristics of the
      sludge collected from the SBRs. The sludge was characterized for morphological
      properties (filament index, floc size), settling, compressibility, suspended
      solids (SS) concentration. The sludge from each plant was different from the
      others in most of the characteristics. One sludge out of six (sludge G) was
      completely different from the others with a very degraded structure and low
      discrete settling and compression. This reactor was not working fully
      satisfactorily with a too high COD at outlet, probably because this SBR was
      undergoing repetitive overloading linked to a very bad recovery of the whey by
      the cheese maker. The five other SBRs were working fully satisfactorily but the
      characteristics of the five sludges were quite different from one sludge to
      another. The size of the flocs seemed to be the only parameter measured which
      could be correlated to the settling characteristics of the sludge. The sludge
      characteristics and the parameter correlations were also compared with that of
      municipal activated sludge and were found to be very different.

PMID- 17506421
TI  - Potential of filter-vermicomposter for household wastewater pre-treatment and
      sludge sanitisation on site.
AB  - Septic tank systems have been widely used to separate and digest solid matter in
      the household wastewater for a long time. However, they contaminate groundwater
      with pathogens and nutrients and deprive agriculture of valuable nutrients and
      soil conditioner from human excreta. Compared with septic tank systems the filter
      composter (Rottebehaelter), which usually consists of an underground monolithic
      concrete tank having two filter beds at its bottom or two filter bags that are
      hung side by side and used alternately at intervals of 6-12 months, is an
      efficient component for solid-liquid separation, pre-treatment and
      collection/storage of solid matter in household wastewater. The solids are
      retained and decompose in the filter bags or on the filter bed while the liquid
      filters through. However, because of the high moisture content of the retained
      solids decomposition is slow. Therefore, secondary treatment of the retained
      solids is required for sanitisation. The breakthrough was the combination of
      vermicomposting with the filter-composter system. Relatively dry and stable
      retained materials were obtained in the filter bags in about 3 months only. No
      secondary treatment is required as the human excreta will be converted to
      vermicastings, which are hygienically safe and can be reused as soil conditioner.
      Therefore, further development of the filter-composter with vermicomposting is
      worthwhile, especially the aspects of sanitisation of the faecal matter and its
      reuse as a soil conditioner.

PMID- 17506422
TI  - Optimization of subsurface vertical flow constructed wetlands for wastewater
      treatment.
AB  - Constructed wetlands (CWs) use the same processes that occur in natural wetlands
      to improve water quality and are used worldwide to treat different qualities of
      water. This paper shows the results of an Austrian research project having the
      main goals to optimize vertical flow beds in terms of surface area requirement
      and nutrient removal, respectively. It could be shown that a subsurface vertical
      flow constructed wetland (SSVFCW) operated with an organic load of 20 g COD x m(
      2) x d(-1) (corresponding to a specific surface area demand of 4 m2 per person)
      can fulfil the requirements of the Austrian standard regarding effluent
      concentrations and removal efficiencies. During the warmer months (May -
      October), when the temperature of the effluent is higher than 12 degrees C, the
      specific surface area might be further reduced. Even 2 m2 per person have been
      proven to be adequate. Enhanced nitrogen removal of 58% could be achieved with a
      two-stage system (first stage: grain size for main layer 1-4 mm, saturated
      drainage layer; and second stage: grain size for main layer 0.06-4 mm, free
      drainage) that was operated with an organic load of 80 g COD x m(-2) x d(-1) for
      the first stage (1 m2 per person), i.e. 40 g COD x m(-2) x d(-1) for the two
      stage system (2 m2 per person). Although the two-stage system was operated with
      higher organic loads a higher effluent quality compared to a single-stage SSVFCW
      (grain size for main layer 0.06-4 mm, free drainage, organic load 20 g COD x m(
      2) x d(-1)) could be reached.

PMID- 17506423
TI  - Anaerobic membrane bioreactor for treatment of synthetic municipal wastewater at
      ambient temperature.
AB  - Non-woven fabric filter and poly-tetrafluoroethylene (PTFE) composite membrane
      were investigated to determine their applicability to treat low strength
      wastewater in an anaerobic membrane bioreactor (AMBR). Sludge cake resistance of
      the membrane was quantified using pure water flux of anaerobic sludge cake
      accumulated on the glass fiber filter of similar pore size. It is hypothesized
      that the formation of thin cake layer on the porous medium, e.g. non-woven and
      PTFE acts as a dynamic membrane. Thus, the capture of thin sludge cake inside the
      non-woven fabric matrix and accumulation on the PTFE membrane surface forms a
      membrane system equivalent to a commercial membrane system. The permeate quality
      was found to improve as the cake became more dense with filtration time. The PTFE
      composite membrane coated with thin PTFE film on the non-woven fabric filter
      enhanced the filtration performance by improving flux and minimizing the
      propensity of bio-fouling. The membrane flux was restored by back-flushing with
      permeate. The AMBR coupled with PTFE laminated membrane was operated continuously
      during the experiment at a cross flow velocity (CFV) of 0.1-0.2 m/sec and a
      transmembrane pressure (TMP) of 0.5-3 psi. Although about a month of acclimation
      was required to reach steady state, the effluent chemical oxygen demand (COD),
      volatile fatty acids (VFAs) as acetic acid, and suspended solids (SS)
      concentrations were below 30, 20 and 10 mg/L, respectively, during 90 days of
      operation with intermittent back washing. The lower operation TMP and CFV were
      subjected to less shear stress on the microbial community during continuous AMBR
      operation. In addition, thin sludge film accumulated on the membrane surface also
      acted as a biofilm bioreactor to remove additional COD in this study.

PMID- 17506424
TI  - Using molecular tools to assess biofilms in onsite systems.
AB  - Onsite sewage treatment is growing in diversity, and in regulatory control across
      Australia. This is occurring for both blackwater and greywater treatment, as the
      drought impact deepens and more of the community are exposed to options for
      'managing' their own water. Regulators in each State are drafting and
      implementing Guidelines to cover a range of on-site system scenarios. In
      addition, more and more decentralised options are being tendered for sewage
      management in the commercial world. In this project we aim to use novel molecular
      tools, in combination with traditional physical/chemical/biological methods, to
      understand onsite treatment in a more detailed manner. The system tested is a new
      peat based biofilter which can be used for greywater or blackwater application,
      and can be retrofitted to current sewage systems. This project has been based on
      the AquaReuse greywater system for demonstration purposes, showing the strength
      of the information gained from the use of novel tools. The two systems
      investigated are installed at a caravan park in New South Wales (NSW) and a
      domestic residence in Tamborine, Queensland (OLD). A 20-week intensive sampling
      and analysis program was followed. The project monitored standard analytes such
      as biochemical oxygen demand (BOD5), suspended solids (SS) and thermotolerant
      coliforms (TC). Additionally, we studied the biological community using
      fluorescent in situ hybridisation (FISH) on a monthly basis and full-cycle
      ribosomal RNA analysis (rRNA) for one sample to assess the biological community
      inhabitants. rRNA analysis at the NSW facility demonstrated a highly diverse
      biological community, in keeping with its long established operating period. In
      contrast, FISH analysis at the OLD installation showed a less diverse and younger
      community. rRNA and FISH identified organisms that are mostly associated with
      nutrient removing functions.

PMID- 17506425
TI  - Development of an empirical mathematical model for describing and optimizing the
      hygiene potential of a thermophilic anaerobic bioreactor treating faeces.
AB  - Poor sanitation and insufficient disposal of sewage and faeces are primarily
      responsible for water associated health problems in developing countries.
      Domestic sewage and faeces are prevalently discharged into surface waters which
      are used by the inhabitants as a source for drinking water. This paper presents a
      decentralized anaerobic process technique for handling of such domestic organic
      waste. Such an efficient and compact system for treating faeces and food waste
      may be of great benefit for developing countries. Besides a stable biogas
      production for energy generation, the reduction of bacterial pathogens is of
      particular importance. In our research we investigated the removal capacity of
      the reactor concerning pathogens, which has been operated under thermophilic
      conditions. Faecal coliforms and intestinal enterococci have been detected as
      indicator organisms for bacterial pathogens. By the multiple regression analysis
      technique an empirical mathematical model has been developed. The model shows a
      high correlation between removal efficiency and both, hydraulic retention time
      (HRT) and temperature. By this model an optimized HRT for defined bacterial
      pathogens effluent standards can be easily calculated. Thus, hygiene potential
      can be evaluated along with economic aspects. In this paper not only results for
      describing the hygiene potential of a thermophilic anaerobic bioreactor are
      presented, but also an exemplary method to draw the right conclusions out of
      biological tests with the aid of mathematical tools.

PMID- 17506426
TI  - Waste stabilization ponds and rock filters: solutions for small communities.
AB  - In temperate climates facultative ponds and rock filters (either unaerated or, if
      ammonia removal is required, aerated) are a low-cost but high-performance
      treatment system for small rural communities. Effluent quality is suitable for
      surface water discharge or, in summer, for restricted crop irrigation. In
      tropical climates anaerobic and facultative ponds and either unaerated rock
      filters or, if ammonia reduction is required, subsurface horizontal-flow or
      vertical-flow constructed wetland, can be used if the effluents are discharged to
      surface waters. However, if the treated wastewater is to be used for crop
      irrigation, then a 3-log unit pathogen reduction by treatment in anaerobic,
      facultative and single maturation ponds is required for both restricted and
      unrestricted irrigation, provided that, in the case of unrestricted irrigation,
      there are in place post-treatment health-protection control measures that
      together provide a further 4-log unit pathogen reduction.

PMID- 17506427
TI  - Comparison of the nutrient removal efficiency of onsite wastewater treatments
      systems: applications of conventional sand filters and sequencing batch reactors
      (SBR).
AB  - When domestic wastewater was treated with different onsite applications of buried
      sand filters and sequencing batch reactors, good organic matter removal was
      common and effluent BOD7 concentrations from 5 to 20 mg/l were easily achievable.
      For total nitrogen, effluent concentrations were usually between 20 and 80 mg/l.
      Good phosphorus removal, even using special adsorption or precipitation
      materials, was difficult to achieve and large variations occurred. The median
      effluent concentration of total phosphorus in the most successful sand filter
      application was less than 0.1 mg/l and other sand filters and SBRs had the median
      concentrations varying from 1.7 to 6.7 mg/l. These results are based on one year
      in situ monitoring of 2 conventional buried sand filters, 6 sand filter
      applications with special phosphorus adsorbing media within the filter bed, 5
      sand filters with separate tertiary phosphorus filtration and 11 small SBRs of
      three different types. The study was carried out in southern Finland during 2003
      05. The whole project included monitoring of more than 60 plants of 20 different
      treatment types or methods, used in normal conditions to treat domestic
      wastewater. Evaluation of the different systems was made by comparing the
      measured effluent concentrations. In addition the effluent concentrations were
      compared to the discharge limits calculated according to the new Finnish
      regulation.

PMID- 17506428
TI  - Modification of submerged membrane bioreactors (MBRS) by inserting baffles: pilot
      scale study.
AB  - Submerged membrane bioreactors (MBRs) have been gaining in popularity in various
      types of wastewater treatment. One drawback of submerged MBRs is difficulty in
      removing nitrogen as they are accompanied with intensive aeration inside the
      reactor and therefore principally operated under aerobic conditions. In order to
      address this problem, a simple modification for submerged MBRs, insertion of
      baffles to create alternative aerobic/anoxic conditions, was proposed. In this
      study, the performance of the proposed baffled membrane bioreactor (BMBR) was
      investigated based on a pilot-scale experiment using a real municipal wastewater.
      With appropriate operating conditions, the BMBR could remove more than 70% of
      total nitrogen contained in the feed water without any external carbon source.
      The BMBR demonstrated a good treatment performance in terms of TOC and phosphorus
      removal as well. Increase of trans-membrane pressure difference was subtle, which
      might be attributed to the alternative creation of aerobic/anoxic conditions.

PMID- 17506429
TI  - Vertical flow constructed wetland for textile effluent treatment.
AB  - A pulse feed vertical flow constructed wetland (VFCW) proved to be efficient in
      the treatment of a textile effluent being able to buffer, dilute and treat an
      Acid Orange (AO7) accidental discharge. The influence of the flooding level (FL)
      and pulse feed (PF) duration on the removal efficiencies of a VFCW was examined.
      Average AO7 removal efficiencies of 70% were achieved for an AO7 Inlet
      concentration of 700 mgl(-1) applied during 15 min cycle(-1) (every three hours)
      at a hydraulic load of 13 lm(-2) cycle(-1) and an FL of 21%. The VFCW was
      modelled by analogy with a combination of ideal reactors. The simplest
      combination that best reproduced the experimental results was an association of 2
      reactors in series plus 1 reactor accounting the dead volumes. The model
      parameters helped to understand the hydrological and kinetic processes occurring
      in VFCW. Through the model simulation it was shown that 3 VFCW in series were
      enough to efficiently treat an organic mass load of 76 gAO7 m(-2) day(-1) in 9
      hours and fulfil the discharge legislation. In this work it was possible to
      establish that the overall degradation kinetics was of first order.

PMID- 17506430
TI  - Biological nutrient removal by applying SBR technology in small wastewater
      treatment plants: carbon source and C/N/P ratio effects.
AB  - SBR technology is considered an alternative to conventional processes such as
      Phoredox, Five-stage Bardenpho, among the others for treating nutrients in
      wastewaters. It is especially applicable to small communities of a just few
      people to a population equivalent (p.e) up to 4000. In this paper, biological
      nutrient removal using SBR technology in a single reactor is presented.
      Biological nutrient removal requires a sequence of anaerobic-anoxic-aerobic
      phases with multiple feeding events over one cycle. This filling strategy was
      adapted to enhance denitrification and phosphate release, using the easily
      biodegradable organic matter from the wastewater. In spite of using this feeding
      strategy, the organic matter concentration can be insufficient. The results show
      that biological nutrient removal was successfully achieved by using only one
      reactor, working with a low organic matter concentration in the influent (C/N/P
      ratio of 100:12:1.8). Nevertheless, when the C/P ratio was lower than 36 g COD x
      g(-1) P-P04, an accumulation of phosphate was observed. After that, the system
      responded quickly and returned to ideal conditions (C/P ratio of 67 g COD x g(-1)
      P-PO4), taking only 15 days to achieve the complete nutrient removal.
      Furthermore, the operational conditions and the synthetic wastewater used
      conferred a selective advantage to polyphosphate accumulating organisms (PAOs)
      over glycogen accumulating non-poly-P organisms (GAOs) as shown by the FISH
      analysis performed.

PMID- 17506431
TI  - Wastewater reclamation through a combination of natural systems (infiltration
      percolation and constructed wetlands): a solution for small communities.
AB  - The decision on technologies used for reclaiming wastewater appears as important
      as a consequence of the implications on the economic, environmental and health
      conditions of societies. The problem arises when deciding how to deal with
      wastewater in small communities, because the costs of implementing and operating
      small, intensive wastewater treatment plants are unacceptable and can lead to
      financing and operation problems. Extensive treatment systems can be a good
      solution, where space is available. This paper presents the combination of two
      soft technologies (infiltration-percolation and constructed wetlands) to treat
      and reclaim wastewater. The obtained results show that the infiltration
      percolation effluent presents a quality enough to be reused for irrigation of
      industrial crops, nurseries, fodder, cereals and oleaginous seeds, ornamental
      flower production; industrial cooling; impoundments, water bodies, and streams
      for recreational use in which the public's contact with the water is not
      permitted; and irrigation of forested areas, landscape areas and restricted
      access areas. Moreover, the combination of infiltration-percolation and
      constructed wetlands increases the list of final reclamation to the following:
      irrigation of pasture for milk or meat animals, crops for canning industry, crops
      not raw-consumed, fruit trees except by sprinkling, aquaculture; and aquifer
      recharge by localised percolation through the soil.

PMID- 17506432
TI  - Wastewater reclamation systems in small communities.
AB  - The demands established in the rules and regulations by the administration in
      Catalonia seem to exclude small communities from wastewater reclamation and
      reuse, due to the comparatively high costs associated with the practice at small
      scale. In the framework of the DRAC project (Demonstration on Wastewater
      Reclamation and Reuse in Catalonia) two different pre-treatment systems, one
      extensive (infiltration-percolation) and another intensive (ring filter), each
      one followed by chlorine dioxide disinfection, were tested in order to be applied
      for small communities wastewater reclamation and reuse. The results of this study
      show that infiltration-percolation systems remove very efficiently physico
      chemical contaminants and microorganisms. The ring filter system does not show a
      significant removal rate of contaminants, The use of infiltration-percolation as
      a pre-treatment for advanced chemical disinfection allows reducing the dose of
      disinfectant and the contact time needed to achieve a specific water quality, and
      diminishes disinfection byproducts (DBPs) generation. Therefore, this reclamation
      line is suitable for small communities due to its efficiency and low cost.
      However, further studies are needed in relation to the removal mechanisms of
      microorganisms, organic compounds in IP systems and the possible DBPs formation
      using chlorine dioxide.

PMID- 17506433
TI  - Integrated constructed wetland systems: design, operation, and performance of low
      cost decentralized wastewater treatment systems.
AB  - Several different types of constructed wetland systems are being used as
      decentralized treatment systems including surface-flow, subsurface-flow, vertical
      flow, and hybrid systems. Archetypical wetland systems have design strengths and
      weaknesses, and therefore it should be possible to design combined (integrated)
      systems to optimize a number of important treatment processes. This study
      provides comparative efficacy data for two integrated wetland treatment systems
      (IWTS) designed to enhance treatment of medium strength wastewater generated from
      a pilot-scale intensive fish farm. Results from the twenty eight months study
      included consistently high removal of COD (84% +) and ammonia nitrogen (93%) in
      both systems. Initially, phosphorus removal was also high (>90%) in both systems,
      but removal efficacy declined significantly over time. Nitrate removal was
      significantly better in the system that provided sequential aerobic and anoxic
      environments. Short hydraulic retention times coupled with sustained removal of
      COD and ammonia indicate that the ReCip components could be a least-cost
      wastewater treatment technology in the decentralized market sector.

PMID- 17506434
TI  - Design and operation of SBR processes for small plants based on simulations.
AB  - The paper firstly presents an experimental study in a SBR pilot plant operated at
      20 degrees C for nitrogen removal from a very small village wastewater. The plant
      consisted of only one reactor fed continuously throughout the day and aerated
      intermittently. Two tests with seven and three intermittences of mixing/aerated
      phases were conducted and verification of the results by simulations of the
      activated sludge model (ASM) was also carried out. The experimental results and
      simulation showed that a wide range of effluent N03-N can be obtained using
      different numbers of intermittences and values of the oxygen transfer coefficient
      (K(L)a). At the same time, the paper presents a design procedure for SBR
      processes based on an iterative process of simulations of the ASM model. After
      the selection of the cycle time, the mixing/aeration pattern, the initial volume,
      the solid retention time, and the duration of the phases, the simulation is
      undertaken, resulting in values for the effluent NH4-N and NO3-N, and the
      suspended solids before settling. Then, the latter parameters are verified to
      match the effluent and settling requirements. As an application of the design
      procedure, the effect on design and operation of different SBR configurations and
      of several operating conditions are analysed in three case studies.

PMID- 17506435
TI  - Grey water treatment in UASB reactor at ambient temperature.
AB  - In this paper, the feasibility of grey water treatment in a UASB reactor was
      investigated. The batch recirculation experiments showed that a maximum total-COD
      removal of 79% can be obtained in grey-water treatment in the UASB reactor. The
      continuous operational results of a UASB reactor treating grey water at different
      hydraulic retention time (HRT) of 20, 12 and 8 hours at ambient temperature (14
      24 degrees C) showed that 31-41% of total COD was removed. These results were
      significantly higher than that achieved by a septic tank (11-14%), the most
      common system for grey water pre-treatment, at HRT of 2-3 days. The relatively
      lower removal of total COD in the UASB reactor was mainly due to a higher amount
      of colloidal COD in the grey water, as compared to that reported in domestic
      wastewater. The grey water had a limited amount of nitrogen, which was mainly in
      particulate form (80-90%). The UASB reactor removed 24-36% and 10-24% of total
      nitrogen and total phosphorus, respectively, in the grey water, due to
      particulate nutrients removal by physical entrapment and sedimentation. The
      sludge characteristics of the UASB reactor showed that the system had stable
      performance and the recommended HRT for the reactor is 12 hours.

PMID- 17506436
TI  - Experimental study on nitrogen components during composting process of feces.
AB  - We measured nitrogen components during composting process of feces in a batch
      test in which sawdust was used as a matrix. Further decomposition rates of fecal
      nitrogen and carbon were obtained in the batch tests of different feces loading.
      In composting material that was a mixture of sawdust and fresh feces, fecal
      organic matter decomposed to CO2 and fecal nitrogen mineralized to ammonia during
      the composting process. The biological response of organic matter and nitrogen in
      the composting material was evaluated by oxygen consumption (OUR) and ammonia
      production that was a sum of volatilized ammonia gas and ammonia remaining in the
      composting material. Since composting material contains two different sources of
      organic matter from feces and sawdust, the OUR by using the sawdust matrix only
      was evaluated in preliminary tests. The fecal contribution to the OUR in the
      composting material was therefore calculated by subtraction of the result in the
      preliminary tests from the one in the composting material. The ammonia production
      from the fecal nitrogen was obtained by the same procedure. The decomposition
      rates of input organic matter in feces were approximately 83 and 70%
      respectively, whereas ammonia production rates were approximately 73 and 58% of
      input fecal nitrogen. There was an interesting time lag of the peak time between
      volatilisation rates of ammonia and CO2 during the composting process while fecal
      carbon and nitrogen simultaneously decomposed to ammonia and CO2 in the
      composting material.

PMID- 17506437
TI  - Anaerobic digestion of blackwater from vacuum toilets and kitchen refuse in a
      continuous stirred tank reactor (CSTR).
AB  - The objective of this research was mesophilic anaerobic digestion of blackwater
      from vacuum toilets (BW) and kitchen refuse (KR) in a CSTR within an ecological
      sanitation system. A detailed investigation of the BW characteristics was carried
      out. Research on anaerobic digestion was performed with CSTR of 101 volume at HRT
      of 10, 15 and 20 days. The digestion of BW at 20 days HRT showed stable
      performance without inhibition effects, in spite of relatively high ammonium
      concentrations. The removal of total and particulate COD was 61% and 53%,
      respectively, and the methane yield 10/CH4/cap/day. The addition of kitchen
      refuse (KR) improved the performance of the CSTR in terms of COD removal
      efficiency and methane yield. At 20 days HRT the removal of total and particulate
      COD increased up to 71% and 67%, respectively, and the methane yield to
      27/CH4/cap/day. The results at 15 days HRT showed similar performance. At HRT of
      10 days, the anaerobic treatment was limited but reached steady state conditions
      at higher VFA concentrations in the effluent, with a decrease of COD removal of
      30 to 33% and of methane yields of 19 to 21%.

PMID- 17506438
TI  - Wastewater treatment with activated pre-clarifier and planted soil filters.
AB  - With a series of buffer tank, activated pre-clarifier (SBR) and planted soil
      filters, it is possible to get a stable degradation and good effluent values in
      the case of unsteady inflow and changing concentrations. In the process presented
      here the activated pre-clarifier is working as a denitrification tank and the
      soil filter as a nitrification reactor. An automatic control manages the storm
      water runoff, the water-recirculation returns the nitrate and provides a minimal
      feed. Experiences with this plant from 1999 to 2005 are given in this paper,
      research has been done in the project "Planted soil filters as a Biotechnological
      Process", founded by the German Federal Environment Foundation (DBU). A full
      scale pilot plant was built to treat wastewater from composting sides, with a 42
      m3 SBR and a bed area of 2 x 550 m2 of the planted soil filters. Now, after six
      years of operation, the results are still satisfactory. Besides this pilot plant,
      landfill leakage and municipal wastewater have been treated in a technical scale
      plant with the same process in an 80 L SBR and 0.75 m2 vertical flow soil filter
      with good results.

PMID- 17506440
TI  - Toxicity of domestic wastewater pH to key species within an innovative
      decentralised vermifiltration system.
AB  - The development of innovative decentralised wastewater treatment systems is
      pertinent to environmental sustainability. However for their appropriate use they
      require significant research and design to ensure they can be relied upon in the
      future and in most cases they have received less attention and research than
      large-scale sewage systems. This study assessed the likelihood of biological
      inhibition and disruption from pH to key species for vermifiltration. The test
      firstly assessed the buffer capacity of a vermicompost + manure media finding it
      had a relatively high buffering capacity for pH. The toxicity after the buffer
      capacity experiment showed that the species would survive between pH levels of
      6.2 and 9.7. At the higher and lower pH levels however the survival of juveniles
      was impaired, probably due to their ability to uptake greater amounts of soluble
      salts and inability to regulate them. Overall the study showed that the tolerance
      of the key vermifiltration species to pH was far less than their survival as
      previously proposed and further research assessing their long-term population
      dynamics in a vermifiltration system with pH is warranted.

PMID- 17506439
TI  - Use of real-time PCR to examine the relationship between ammonia oxidizing
      bacterial populations and nitrogen removal efficiency in a small decentralized
      treatment system 'Johkasou'.
AB  - The aim of this study was to examine the relationship between ammonia oxidizing
      bacterial populations and biological nitrogen removal in a small on-site domestic
      wastewater treatment system "Johkasou". The population dynamics of ammonia
      oxidizing bacteria (AOB) in six full-scale advanced Johkasous was surveyed using
      real-time PCR assay over a period of one year. These Johkasous were selected to
      compare the AOB populations in different treatment performance. When the effluent
      NH4-N concentration was higher than 2 mg L(-1), it was difficult to meet the
      effluent standard of advanced Johkasous (T-N 10 mg L(-1)). In contrast, the
      nitrogen removal efficiency was hardly affected by nitrite oxidation and
      denitrification in these systems. In other words, ammonia oxidation was a rate
      limiting step. Furthermore, we focused on the relationship between NH4-N loading
      per AOB cell and nitrogen removal. Real time PCR monitoring results demonstrated
      that it is important to regulate NH4-N loading per AOB cell below 210 pg cell(-1)
      day(-1) to meet the effluent standard of advanced Johkasou. It is considered that
      NH4-N loading per AOB cell is a useful parameter for determining suitable
      nitrogen loading and small decentralized system design.

PMID- 17506441
TI  - Tertiary filtration in small wastewater treatment plants.
AB  - Tertiary filtration can be proposed in small wastewater treatment plants with
      impact on protected water bodies. Rotating disk filters may be adopted, in
      respect to conventional sand filters, when low availability of space and low
      investment costs are the prevailing conditions. The overall objective of this
      research was to evaluate the filtration efficiency of rotating disk filters; to
      compare effectiveness with traditional sand filters; to analyse thoroughly the
      importance of particle size distribution in wastewater tertiary filtration. In
      the experimental activity, conventional wastewater quality parameters were
      investigated and particle size distribution (PSD) was characterized to discuss
      the filter effectiveness. The effect of design and operation parameters of
      tertiary filters were discussed related to particle removal curves derived from
      particles counts. Analysis of particle size distribution can be very useful to
      help comprehension of filtration processes, design of filtration treatments and
      to decide the best measures to improve filter performance.

PMID- 17506442
TI  - Wastewater infiltration percolation for water reuse and receiving body
      protection: thirteen years' experience in Spain.
AB  - Infiltration percolation (IP) is an extensive technology to treat primary or
      secondary effluents of small and middle size communities before reuse or disposal
      to sensitive receiving bodies. Thirteen years of implementation of IP in Spain
      has highlighted the necessity to abide by defined design and construction rules
      and operation conditions in order to achieve consistently the treatment
      objectives and guarantee a long lasting treatment capacity. From this experience,
      high care should be taken of (i) the characteristics of the sand constituting the
      filter, (ii) the drainage conditions, (iii) the influent spreading over the
      infiltration surface and (iv) the risks related to recurrent overloading. Simple
      monitoring measures are suggested in order to improve the reliability of IP
      plants.

PMID- 17506444
TI  - Biological nitrogen removal with three different SBBR.
AB  - In order to compare the performance of biofilms growing on different support
      media, three reactors were fed with municipal wastewater from the city of
      Garching, Germany, and operated under the sequencing batch procedure. The support
      media tested have the commercial names of Kaldnes, polyethylene special support
      for moving bed reactors with approximate diameter of 12 mm; Liapor, ceramic
      spheres with diameters between 4 and 6 mm; Linpor, plastic foam cut in cubes of
      15 mm. The bench-top reactors were tested for COD, TSS and ammonia nitrogen
      removal. During 452 days runs with organic loads between 0.5 and 8.0 gCOD/m2 x d
      were tested. Thin biofilms (Kaldnes and Liapor) perform better for COD and
      ammonia removal under lower organic loading values (< 2.5 gCOD/m2 x d). For
      organic loads over 3.0 gCOD/m2 x d, the reactor packed with Linpor (thick
      biofilm) showed a better COD and ammonia nitrogen removal than the other two.
      Linpor achieved the highest NOx-N production reaching values between 15 and 20
      mg/l. For low organic loading rates Linpor and Liapor present similar average NOx
      N concentrations. Kaldnes shows the lowest concentrations throughout the whole
      experimental period. The difference between ammonia nitrogen removal and NOx-N
      generation is simultaneous denitrification inside the deep biofilms. The average
      mean cellular retention times were 5.4 days for Liapor, 10.0 days for Kaldnes and
      22.9 days for Linpor. This is the reason why Linpor achieved complete
      nitrification even with higher organic loads.

PMID- 17506443
TI  - Treatment of organic synthesis wastewater using anaerobic packed bed and aerobic
      suspended growth bioreactors.
AB  - The performance of an anaerobic mesophilic packed bed reactor, with a mixture of
      GAC and tezontle, followed by an aerobic suspended growth system was studied for
      the treatment of organic chemical wastewater with a high COD concentration (22-29
      g/L). The testing of the anaerobic-aerobic system was conducted in an
      experimental set-up for almost 2.5 years. Different operational conditions were
      evaluated. The anaerobic reactor showed performance stability and COD removals
      higher than 80% were obtained with loads up to 16.6 kg x m(-3) x d(-1). The
      acclimation of the aerobic biomass to the substrate in the anaerobic effluent was
      very quick and COD removals higher than 94% were obtained even at high organic
      loads. The combined anaerobic-aerobic system allowed total COD removals higher
      than 99.5% and the accomplishment of the discharge requirements of 200 mgCOD/L
      when the anaerobic reactor was operated with loads of 8-11 kg x m(-3)x d(-1) and
      the aerobic reactor with 0.33 kg x kg(-1) x d(-1), being the total HRT of 4.4.
      The average TKN removal in the anaerobic-aerobic system was 97%, the average for
      the anaerobic reactor being 52% and that one for the aerobic system being 94%.

PMID- 17506445
TI  - Biological aerated filtration of municipal wastewater using a low-cost filtration
      media.
AB  - The main objective of this research was to demonstrate that selected natural lava
      stones can be successfully used for low-cost aerobic biofiltration of municipal
      wastewater. To demonstrate the procedure a pilot filter was built using 6 mm lava
      stones as support material. The filter depth was 3.0 m. Provided with sampling
      ports at different depths analysis of the wastewater could be made for COD, TSS,
      ammonia and nitrates nitrogen, pH, temperature and Kjeldahl nitrogen. Backwashing
      was performed every 72 hours. Total and dissolved COD and TSS behaved similarly
      with the organic load: The highest removal rates were observed with the lowest
      organic load of 0.8 kgCOD/m3 d. These removal rates decreased to a minimum value
      at organic loading rates of 1.5 kgCOD/m3 d and then remained without noticeable
      changes to the highest value of 3.5 kgCOD/m3 d. The highest total and dissolved
      COD removal values were 81 and 84%, respectively. For TSS the best removal value
      was 95%. Up to 75% ammonia removal was achieved at the lowest organic load of 0.8
      kgCOD/m3 d. Ammonia removal decreased to 36% with a higher organic load of 1.6
      kgCOD/m3 d. The Mean Cellular Retention (MCRT) time varied from 1 to 6 days with
      an average of 3.2 days. This fact proves that the MCRT depends on the backwashing
      frequency more than of any other factor involved. The bed volume decreased in
      about 5% after 300 days of operation. Microscopic observations showed that the
      small stones were rounder after 300 days and that the volume losses were caused
      when the edges of the stones were cut by the abrasion caused by backwashing.

PMID- 17506446
TI  - 2008 Medicare advantage cap rates will rise 3.5%.

PMID- 17506447
TI  - Prescription drugs change healthcare spending patterns.

PMID- 17506448
TI  - Geography has major impact on insurance, health costs.

PMID- 17506449
TI  - Use RVUs to analyze your capitated revenue, improve collections in practices with
      mixed reimbursement.

PMID- 17506450
TI  - Electronic claims settlement tool improves administration of capitated Medicaid
      HMOs.

PMID- 17506451
TI  - Medicare HMO penetration shifts stroke deaths from hospitals.

PMID- 17506452
TI  - Root filling or implant? General considerations.

PMID- 17506453
TI  - Diagnosis and management of non-dental orofacial pain.
AB  - Careful history-taking improves diagnosis of non-dental orofacial pain, a not
      uncommon group of conditions. Accurate diagnosis of conditions such as chronic
      idiopathic facial pain, temporomandibular disorders, burning mouth syndrome and
      trigeminal neuralgia is essential if inappropriate dental treatment is to be
      avoided. There are few investigations to help in the diagnostic process and many
      of these patients have other forms of chronic pain. All the conditions are best
      treated using a holistic approach. Drugs, such as tricyclic antidepressants and
      anticonvulsants, are often effective and surgery can be highly successfully in
      trigeminal neuralgia. Patient education is paramount. CLINICAL RELEVANCE:
      Although the majority of pain seen in general dental practice is dental in
      origin, chronic non-dental orofacial pain must be recognized as its management is
      entirely different.

PMID- 17506454
TI  - Crown and bridge disassembly--when, why and how.
AB  - Crown and bridgework has a finite life span and fails for a number of reasons.
      Removal is often by destructive means. There are a number of clinical
      circumstances, however, in which a conservative disassembly would aid the
      practitioner in completing restorative/endodontic procedures. The aims of this
      paper are to provide a classification for crown and bridge removal systems;
      describe how a number of such systems work; and when and why they might be
      considered. CLINICAL RELEVANCE: Crown and bridge removal is a frequent occurrence
      for dentists. There are many situations in which salvaging extracoronal
      restorations may be more helpful than their destruction.

PMID- 17506455
TI  - Smile aesthetics.
AB  - The aim of this article is to outline some of the factors practitioners should
      take into consideration when planning optimal smile aesthetics. The components of
      the smile that will be discussed include the smile arc, incisor/gingival display,
      smile width, gingival aesthetics, tooth proportionality/symmetry,
      contacts/connectors/embrasures and the dental midlines. CLINICAL RELEVANCE: A
      systematic evaluation of the components of the smile when planning treatment will
      help to improve smile aesthetics and produce greater patient and dentist
      satisfaction.

PMID- 17506456
TI  - Conservative aesthetic techniques for discoloured teeth: 2. Microabrasion and
      composite.
AB  - The first article in this series discussed the minimal intervention approach to
      discoloured teeth, starting with dental bleaching. This second article goes on to
      explain the technique of microabrasion and the use of direct composite
      techniques. CLINICAL RELEVANCE: Microabrasion and composite can provide minimally
      invasive treatments for discoloured teeth.

PMID- 17506457
TI  - Current indications and methods of periodontal splinting.
AB  - The paper discusses the reasons for using periodontal splints, together with
      advantages and disadvantages of their use. Different splinting techniques and
      criteria for selecting the most appropriate method are described. The need for
      care in planning treatment is emphasized. It is essential that, if the degree of
      attachment loss is such that splinting is likely to be needed, this is taken into
      account in the treatment planning at an early stage. CLINICAL RELEVANCE: Used
      correctly, periodontal splinting can greatly improve the comfort, prognosis and
      outcome for a patient with serious periodontal disease. But used incorrectly,
      splinting can cause further deterioration in periodontal health.

PMID- 17506458
TI  - Treatment of temporomandibular disorder in a viola player--a case report.
AB  - Viola and violin players seem to be predisposed to TMD. This case report
      illustrates an example where this occupation caused problems and required
      treatment. The case was managed with a modified Anterior Repositioning Splint
      (ARPS) that the patient wore while playing. CLINICAL RELEVANCE: Temporomandibular
      disorders (TMD) are common within the population. Certain factors can predispose
      or make one more susceptible. This case report highlights viola players who are
      predisposed to TMD.

PMID- 17506459
TI  - Management of a patient with a failed transmandibular implant.

PMID- 17506461
TI  - Physical signs for the general dental practitioner. Case 43. Beau's lines.

PMID- 17506460
TI  - 101 comments.

PMID- 17506462
TI  - Aspects of human disease. 10. Diabetes mellitus.

PMID- 17506463
TI  - Oral piercing: dental considerations and the legal situation in Spain.
AB  - Body piercing has become increasingly popular in Western countries, especially
      among young people. However, not everyone is aware of its potential risks, which
      may develop local and systemic complications shortly after, or long after the
      piercing procedure. Given that the oral cavity is one of the most frequent sites
      for piercing placement, the aim of this paper is to familiarise the oral
      healthcare professional with oral piercing and its possible sequelae in order to
      educate patients prior to and after piercing practices and address any
      complications that may arise.

PMID- 17506464
TI  - Dental antibiotic prescription in Fijian adults.
AB  - AIM: To identify and evaluate dentists' knowledge of and prescription patterns of
      antimicrobial drugs. PARTICIPANTS: All 80 registered general dental practitioners
      in the Republic of The Fiji Islands, excluding academic staff at Fiji School of
      Medicine. Sixty five (81%) usable replies were received and analysed. RESULTS:
      Daily prescription of antibiotics increased with years in practice. There was a
      moderate level of knowledge regarding specific indications for antibiotic
      prescription both therapeutically and prophylactically. There was a tendency
      towards over-prescription with lower dosage, broad spectrum antibiotics with
      amoxycillin being the overwhelming choice. Some under prescription was noted in
      certain surgical scenarios. There was a lack of knowledge of the incidence of
      adverse reactions and very poor medical history record taking. Approximately one
      third of respondents felt antibacterial resistance is a problem in Fiji and 40%
      reported experiencing some form of antibiotic resistance in clinical practice.
      CONCLUSION: Overall there was a moderate level of correct knowledge for
      antibiotic prescribing of dentists in Fiji. An improved section on oral and
      dental infections including guidelines for children should be included in the
      Fiji Antibiotic Guidelines which could be distributed to all dentists.

PMID- 17506465
TI  - Effects of toothbrush size and dentifrice type/brand on pea-sized and larger
      amounts of dentifrice.
AB  - PURPOSE: To assess the effects of toothbrush size and dentifrice type/brand on
      amounts of dentifrice being placed when trying to replicate pictures with
      different amounts of dentifrice, including a pea-sized amount. METHODS: This
      laboratory trial used one researcher to repeatedly dispense five dentifrice
      products on three different child-sized toothbrushes using a standard procedure.
      Two sets of drawings, depicting the recommended pea-sized and larger amounts,
      were used as guides in an effort to place the same amount each time. Data were
      analysed using ANOVA. RESULTS: Amounts of dentifrice placed on the two larger
      toothbrushes were significantly greater than those placed on the smallest
      toothbrush (p < 0.0001). The amounts placed on the two larger toothbrushes with
      similar brushing areas but different shapes were not significantly different from
      each other. The effect of dentifrice type/brand varied in each analysis. For pea
      sized amounts, one of 10 pairwise comparisons was significant. For amounts larger
      than pea-sized, another pair of the 10 pairwise comparisons was significant.
      However, there was no significant effect of dentifrice type/brand when
      considering both pea-sized and larger amounts together in the same analysis.
      CONCLUSIONS: Toothbrush size significantly affected the amount of dentifrice
      placed for both pea-sized and larger amounts. The amounts placed on larger size
      toothbrushes were greater than on the smaller size toothbrush. No consistent
      effects of selected dentifrices were found.

PMID- 17506466
TI  - Glycemic effect of administration of epinephrine-containing local anaesthesia in
      patients undergoing dental extraction, a comparison between healthy and diabetic
      patients.
AB  - OBJECTIVES: To compare the effect of administration of epinephrine (in the dental
      local anesthetic solution) on blood glucose concentration in healthy and diabetic
      dental patients after extraction. To determine if there is any correlation
      between blood glucose level changes and the number of carpules injected, number
      of teeth extracted and the gender of the patient. MATERIALS AND METHOD: An open
      study of 60 patients (30 healthy and 30 diabetics) visiting the Oral Surgery
      clinic of Ajman University of Science and Technology. A drop of blood was taken
      from the tip of the patient's finger and placed on a glucometer strip to
      determine the pre-operative blood glucose level. Dental local anaesthesia (1.8 ml
      carpule each) containing 1:80,000 epinephrine was injected either through
      infiltration or block. Extraction was carried out atraumatically and 10 minutes
      post-extraction the glucose measurement was taken. RESULTS: The difference in the
      blood glucose levels pre- and post operatively were not significantly different
      (p > 0.05) when a comparison was made between the healthy and diabetic groups.
      Comparison of glucose changes in diabetics who had taken their hypoglycaemic
      medication and those who had not, showed a significant difference (p < 0.05).
      Statistical analysis showed no correlation between the blood glucose level
      changes and the number of carpules used, number of teeth extracted and gender.
      CONCLUSION: Dental local anaesthetic solution containing epinephrine is safe to
      use in all healthy and diabetic patients (irrespective of their gender),
      excepting those diabetics who have not taken their pre-operative hypoglycaemic
      medication. There is no relation between the post-extraction glucose changes and
      the number of carpules used, number of teeth extracted or gender.

PMID- 17506467
TI  - An Arabic version of the Oral Health Impact Profile: translation and psychometric
      properties.
AB  - OBJECTIVES: To translate the original English version of the Oral Health Impact
      Profile (OHIP) into an Arabic version, and to investigate the psychometric
      properties of the translated instrument among adults in Saudi Arabia. METHODS:
      The original English version of OHIP with 49 items was translated into Arabic
      following accepted cultural adaptation technique guidelines using a forward
      backward method. After pilot testing, the instrument was administered to 426
      adults in Saudi Arabia. RESULTS: A priori hypothesised associations between the
      OHIP summary score, self-reported oral health and five oral disorders were
      confirmed in a convenience sample of the general population (n = 356). These
      associations were interpreted as support for construct validity. The instrument's
      responsiveness, as indicated by a mean OHIP summary score change from 62.27 to
      14.00, was established in 30 consecutive patients treated for complete and
      removable partial dentures. Test-retest reliability was demonstrated by
      intraclass correlation coefficients of 0.75 - 0.90 for dimensions and summary
      score (n = 40). Internal consistency was high (Cronbach's alpha > 0.74) in the
      general population sample. CONCLUSION: Sufficient psychometric properties of the
      OHIP-A make the instrument suitable for assessment of oral health-related quality
      of life in Saudi Arabia.

PMID- 17506468
TI  - Oral health in rural and remote Western Australian indigenous communities: a two
      year retrospective analysis of 999 people.
AB  - AIM: Remoteness is a significant factor determining the level of basic health,
      education and infrastructure services to which Aboriginal people have access.
      This study examines the oral health status and oral health behaviours of
      Aboriginal people attending rural and remote dental clinics. METHODS: Data were
      collected as part of routine delivery of dental services in five rural and remote
      dental clinics. RESULTS: The average DMFT score of patients in all the clinics
      was 8.5 (sd 6.6). Advanced periodontal disease (a CPI score of 3 and/or 4) was
      present in 60.8% of all patients. Almost 88% of patients had experienced
      toothache in the previous six months. Almost a third (31.4%) of people could not
      remember the last time they went to the dentist. Less than half of the people
      reported brushing their teeth daily (40.4%) with 37.9% cleaning occasionally. A
      total of 52.4% of patients identified themselves as a 'smoker' of tobacco
      products. Past smokers accounted for 10.5% of the participants. The most common
      self-reported reason for visiting the clinic was for 'hole in tooth/fillings
      required' (37.4%), followed by 'pain/urgent problem' (24.8%). CONCLUSIONS: This
      study emphasises the urgent need for the development of strategies targeting
      Aboriginal oral health, both as stand alone, and as part of a multifactorial risk
      factor approach where oral health is integral to general health activities.

PMID- 17506469
TI  - Fractured incisors: a judicious restorative approach--Part 2.
AB  - AIM: To consider different conservative options in the literature to restore
      fractured anterior teeth. MATERIALS AND METHODS: Only anterior tooth fractures
      not involving the pulp were considered, without limitation on age. Treatment
      options were chosen depending on the clinical situation of patients at first
      visit. The authors considered 15 cases each of: reattachment; porcelain veneers;
      direct composites. RESULTS AND CONCLUSIONS: The techniques analysed were revealed
      to be valid during the period of observation. No failures were recorded with
      vital teeth keeping their vitality and no radiographic signs of apical or root
      pathology. With reattachment, two cases have shown the visibility of fracture
      line after two years, depending on the angle of light incidence on the tooth
      surface. For direct restorations, three adult cases have shown partial
      discolouration at 24, 28 and 40 months. No fractures or debonding have occurred
      among porcelain veneers. The authors suggest, whenever possible, to utilise the
      reattachment technique. Direct restorations are suitable for young patients: they
      have a higher chance of sustaining further trauma than adults, and composites
      have a favourable failure mode compared to ceramics. In adults, where long
      lasting restorations are needed, restoration with porcelain veneers is the
      treatment of choice.

PMID- 17506470
TI  - Continuing education: obligation or duty? The European dilemma.
AB  - Continuing dental education is now a professional and ethical obligation. The
      practising dentist has the responsibility to be a continuous learner by
      participating in educational programmes. This requirement for a career long
      education system provides awareness to the public that the dental profession is
      dedicated to the maintenance of high evidence-based education and permanent
      research into the best quality standards. Numerous European countries are
      involved in this process in an attempt to harmonise basic guidelines.

PMID- 17506471
TI  - Reliability, validity, incidence and impact of temporormandibular pain disorders
      in adolescents.
AB  - The first aim of this thesis was to investigate the prevalence of
      temporomandibular disorder (TMD) pain in adolescents an a Swedish county and
      whether there were differences in patient age and gender and in treatment given
      for TMD pain by dentists in Public Dental Service (PDS) clinics. The
      epidemiological variable TMD-S was introduced in the PDS in Ostergotland County,
      Sweden, in 2000 and is recorded for all adolescents aged 12-19 at the annual
      routine examination. Self-reported TMD pain in this investigation was based upon
      the response of the subjects to two questions: (1) Do you have pain in your
      temples, face, temporomandibular joint, or jaws once a week or more? and (2) Do
      you have pain when you open your mouth wide or chew, once a week or more? Dental
      records of 200 patients with TMD pain were randomly selected from the population
      to evaluate treatment given for TMD. Among 28,899 participating adolescents, 4.2%
      reported TMD pain. Prevalence increased with age, a significant difference was
      seen between boys and girls, and 34% of patients with TMD pain received TMD
      relared treatment in dental clinics. The second aim was to evaluate the
      reliability and validity of self-reported TMD pain in 120 adolescents, 60 with
      self-reported TMD pain and 60 age- and sex-matched controls without TMD pain. All
      adolescents were examined twice at a PDS clinic. At the first examination, self
      reported TMD pain was recorded for each patient. At the second examination, a
      clinical examination was made blind to the patients' self-report of pain
      symptoms, after which self-reported TMD pain was again recorded. The clinical
      examination was based upon the Research Diagnostic Criteria for TMD (RDC/TMD).
      Test-retest reliability of 0.83 (kappa) was found for the two questions.
      Sensitivity was 0.98 and specificity 0.90 for assessments made on the same day
      and 0.96 and 0.83, respectively, for assessments made 2-4 weeks apart. The third
      aim was to evaluate incidence, by age and gender, and temporal patterns of TMD
      pain in adolescents. This 3-year longitudinal study was carried out at all PDS
      clinics from 2000 to 2003. All individuals aged 12-19 years in the county who
      visited the clinics for annual examinations were eligible for the study. Overall,
      the annual incidence of TMD pain among 2255 participating adolescents was 2.9%.
      Incidence among girls (4.5% was significantly higher than in boys (1.3%).
      Incidence increased with age in girls and boys, although less so in boys. These
      adolescents were re-examined annually for 3 years, and a fluctuating pattern of
      TMD pain was common. The fourth and final aim was to investigate gender and age
      differences in pain behavior, jaw function, and psychosocial status in
      adolescents with self-reported TMD pain. A postal questionnaire was sent to 350
      consecutive patients with self-reported TMD pain and 350 healthy age- and sex
      matched individuals aged 12-19 years 2-4 weeks after their annual dental
      examination. The groups were divided into younger (age 12-15) and older (age 16
      19) groups. The TMD and control groups differed significantly in most variables
      related to pain characteristics and psychosocial and behavioral factors. Multiple
      pain sites were significantly more common in the TMD than in the control group,
      but there were no gender differences. For adolescents reporting pain once a week
      or more, no gender differences were seen in pain intensities. Jaw function
      limitation, depression scores, and perceived need for TMD treatment were
      significantly higher overall in girls than in boys. Almost one-third of older
      girls, compared to one out of ten older boys, reported school absences and
      analgesic consumption because of their TMD pain. Older girls had significantly
      higher Graded Chronic Pain Scale scores than older boys. In conclusion, TMD pain
      increases with increasing age in adolescents and is more common in girls than in
      boys. A fluctuating pain pattern can be seen. TMD-S, with two self-report
      questions, has very good reliability and validity, and can be recommended for
      screening adolescents for TMD pain. TMD pain seems to have a greater Impact on
      girls than boys. particularly in ages 16-19 years.

PMID- 17506473
TI  - Comparison of immunoradiometric assays for determination of thyroglobulin: a
      validation study.
AB  - In this study we compared and validated commercial immunoradiometric assays
      (IRMA) to determine thyroglobulin (Tg) levels in serum. From a set of 440
      samples, 68 were selected to calculate the validation parameters and the clinical
      performance of the assays. The commercial kits evaluated were the Tg-CTK
      (DiaSorin), IRMAZenco Tg (ZenTech), and SELco-Tg (Medipan). We found that 21% of
      the collected samples were in the critical range of concentration. Detection
      limits were calculated as being below 3 microg/L. Intra- and inter
      reproducibility were lower than 3.1% and 9.2%, respectively. Dilution and
      recovery studies provided quantitative determinations. Correlation regression
      coefficients from the results of the methods were obtained. The determined
      concentrations were compared with the clinical evidence of disease. Variation in
      the 125-iodine-labeled antibody concentration and control charts showed the
      robustness of the methods. Analysis time and the simplicity of the methods were
      also evaluated. Reliable Tg determination is important for monitoring patients
      with differentiated thyroid cancer (DTC), controlling other thyroid diseases, and
      assessing the quality of imaging techniques. A strategy for verification and
      comparison based on analytical parameters and clinical performance is proposed.

PMID- 17506474
TI  - Prevalence of high antibody titers of pertussis in Turkey: reflection of
      circulating microorganism and a threat to infants.
AB  - Acute pertussis infection among adults can cause its transmission to the larger
      population, especially to infants and young children, who can develop severe
      disease. In order to determine an age-dependent pertussis immune response, anti
      pertussis toxin (PT) antibody was detected by the indirect enzyme-linked
      immunosorbent assay (ELISA) method in serum samples from 2,085 healthy subjects
      ranging in age from 6 months to > or = 60 years. Also included in the evaluation
      were responses to a questionnaire including sociodemographic characteristics,
      vaccination, and infection history. Titers of 50-99 ELISA units (EU)/mL and of >
      or = 100 EU/mL were accepted as indicative for recent exposure or infection. In
      addition, 30 EU/mL was estimated to be a sufficient titer in women of
      childbearing age to protect their newborns until administration of their first
      dose of pertussis vaccine. After the age of 4-5 years, presence of high-titered
      antibodies that increase with age might be a reflection of circulating infection
      and indicate the magnitude of the threat to infants. According to the
      questionnaires, in the groups younger than 15 years old, three to four doses of
      diphtheria toxoid-whole cell pertussis-tetanus toxoid (DwPT) were administered in
      47.2 to 77.4%, 91.2 to 100.0%, and 83.5 to 100.0% of participants in Diyarbakir,
      Samsun, and Antalya, respectively. In addition, up to half of the expectant
      mothers we studied lacked a sufficient level of estimated antibody titers. To
      protect infants from life-threatening pertussis infection, improving vaccination
      coverage to ensure herd immunity and uniformly establishing coverage throughout
      the country are essential. Furthermore, revaccination with acellular vaccine for
      schoolchildren as well as for the households of pregnant women is recommended.

PMID- 17506475
TI  - Association between vitamin-D receptor gene FokI polymorphism and Graves' disease
      among Taiwanese Chinese.
AB  - 1,25(OH)(2)D(3), exerting its biological effects through the vitamin-D receptor
      (VDR), plays a role in the modulation of the human immune system. The aim of this
      study was to test for the presence of an association between VDR gene
      polymorphism and the susceptibility to Graves' disease (GD) for Taiwanese
      Chinese. Using a polymerase chain reaction (PCR)-based restriction analysis, we
      screened the VDR exon 2 start codon T/C (VDR-FokI) polymorphism to determine the
      genotypes for 88 GD patients and 90 normal controls. From the genotype analysis,
      GD patients featured a greater proportion of the CC genotype (44.3%) and a
      smaller proportion of the TT genotype (12.5%) than was the case for normal
      controls (CC: 23.3% and TT: 28.9%; chi-squared test, P=0.003). The odds ratios
      (ORs) for the risk of the CC genotype's appearance compared with the
      corresponding values for the TT and TC genotypes, for the GD patient group, were,
      4.39 (95% confidence interval [CI]: 1.82-10.61) and 2.10 (95% CI: 1.06-4.18),
      respectively. With respect to the allelic analysis, we observed significantly
      increased C-allele (65.9%) and decreased T-allele (34.1%) frequencies among GD
      patients compared to normal controls (C: 47.2% and T: 52.8%; chi-squared test,
      P=0.002). The OR for the risk of appearance of the C allele in the GD-patient
      group was 1.93 (95% CI: 1.27-2.95). In conclusion, the VDR-FokI T/C polymorphism
      might be able to be used as a genetic marker to predict the likelihood of GD
      development.

PMID- 17506476
TI  - Risk analysis of coronary heart diseases in Korean adults by using the National
      Cholesterol Education Program Adult Treatment Panel III.
AB  - The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP
      III), updated in 2001, quantified the risk factors and made it possible to assess
      risks for metabolic syndrome (MS) and coronary heart diseases (CHD). Many
      reported the prevalence of MS by NCEP ATP III in Orientals but few did risk
      analysis of CHD. We investigated the risk of CHD in Korean adults and the
      distribution of population for therapeutic lifestyle change (TLC) and drug
      therapy according to the NCEP ATP III guidelines. Based on ATP III risk factors,
      estimates of the 10-year risk for CHD on 16,383 Koreans and the distributions of
      population for the TLC and additional drug therapy by sex and age were
      calculated. High-, intermediate-, and low-risk groups were 8.1%, 24.1%, and
      67.8%, respectively; 12.1% (high-, intermediate-, and low-risk groups: 32.0%,
      45.1%, and 6.0%, respectively) needed TLC and 6.1% (high-, intermediate-, and low
      risk groups: 39.4%, 16.6%, and 1.3%, respectively) needed additional drug
      therapy. The groups with higher risk needed more TLC and drug therapy. In the
      same age group, the rates of high risk in men showed a 1.0-6.6 fold increase
      compared with those in women. In Koreans, those who needed TLC and drug therapy
      were substantially lower than those in Americans.

PMID- 17506477
TI  - Preliminary clinical measurement of the expression of B-cell activating factor in
      Chinese systemic lupus erythematosus patients.
AB  - It has recently been found that excessive serum B-cell activating factor (BAFF)
      production triggers severe autoimmune disorders in mice resembling systemic lupus
      erythematosus (SLE). Whether such dysregulation in circulating levels of BAFF
      results from overexpression of BAFF gene in clinical patients with SLE is still
      unclear. In this study, we investigated the relationship between the expression
      of BAFF and SLE. Here, circulating levels of BAFF were measured in 59 Chinese
      patients with SLE using enzyme-linked immunosorbent assay (ELISA). In addition,
      we have quantified the specific mRNA levels of BAFF in unstimulated peripheral
      blood mononuclear cells (PBMNCs) using real-time polymerase chain reaction (PCR).
      Serum samples of all SLE patients were also assayed for quantitative
      immunoglobulins (IgG, IgA, IgM) and anti-double-stranded DNA (anti-dsDNA)
      antibody levels, and compared with samples from 40 healthy control subjects.
      Serum BAFF levels in all SLE patients were significantly elevated (P<0.001) and
      correlated with the levels of IgG and the titers of anti-dsDNA antibody (r=0.442,
      r=0.85, P<0.00). More importantly, 66% (39/59) of these SLE patients had
      significantly higher levels of blood BAFF mRNA, closely paralleling with serum
      BAFF levels (r=0.652, P<0.001). Dysregulation of BAFF is relatively common in
      Chinese patients with SLE. Excessive serum BAFF production may result from
      overexpression of the BAFF gene. BAFF also plays an important role in activating
      specific autoreactive B cells and modulating the production of autoantibodies.

PMID- 17506478
TI  - Turbidimetric carbamazepine immunoassay on the ADVIA 1650 and 2400 analyzers is
      free from interference of antihistamine drugs hydroxyzine and cetirizine.
AB  - A recent report indicates that hydroxyzine and its active metabolite cetirizine
      interfere with the particle-enhanced turbidimetric inhibition immunoassay
      (PENTINA) carbamazepine assay. We studied potential interference of hydroxyzine
      and cetirizine with the turbidimetric carbamazepine immunoassay on ADVIA 1650 and
      ADVIA 2400 (Bayer Diagnostics, Tarrytown, NY) analyzers. Aliquots of drug-free
      serum pools were supplemented with various concentrations of hydroxyzine and
      cetirizine representing therapeutic, moderate toxic, as well as very toxic
      concentrations. These samples were assayed by the turbidimetric carbamazepine
      immunoassay on two analyzers. To study the interference in presence of the
      analyte, aliquots of a serum pool prepared from patients receiving carbamazepine
      were further supplemented with various amounts of hydroxyzine and or cetirizine
      and apparent carbamazepine concentrations were measured again in order to compare
      with the value of original pool. No apparent carbamazepine concentration was
      observed when aliquots of drug-free serum were supplemented with hydroxyzine or
      cetirizine. Moreover, in the carbamazepine pool, the original carbamazepine
      concentration compared well when aliquots of this serum pool were further
      supplemented with hydroxyzine or cetirizine. We conclude that the turbidimetric
      carbamazepine immunoassay is free from interference of hydroxyzine and
      cetirizine.

PMID- 17506479
TI  - Improved method to calculate the antibody avidity index.
AB  - The methods currently used to determine the immunoglobulin avidity index (AI)
      require the choice of a reference point in the ELISA titration curve. Since both
      curves, with and without denaturating reagents, seldom run in parallel, the AI
      value becomes highly dependent on this reference. The new method for AI
      calculation presented here takes into account the whole data of the ELISA
      titration curve in which the final numerical AI is the average of each point.

PMID- 17506480
TI  - High-molecular intestinal alkaline phosphatase by agarose gel electrophoresis.
AB  - The presence of high-molecular intestinal ALP (HIALP) overlapping with bone ALP
      in the alpha(2)beta region has been demonstrated. In this study we evaluated a
      method of separating HIALP after its conversion into ALP(5) by the action of
      protease. Serum samples from patients were mixed with protease at a ratio of 5:1
      and left at room temperature for more than 30 min. The protease-treated and
      nontreated samples were both subjected to agarose gel electrophoresis. Patients
      who showed a decrease in ALP(3) in the alpha2beta region and an increase in
      ALP(5) in the beta region were regarded as HIALP-positive. HIALP was observed in
      26.7-33.1% of patients with liver diseases, collagen diseases, and diabetes
      mellitus. Renal disease was ABO blood group-dependent and showed high positive
      rates for blood groups B and O. The HIALP-positive rate was low (7.1-15.5%) in
      patients with cardiovascular diseases, malignant tumors, and other disorders.
      ALP(5) was also observed in 98.4% of HIALP-positive patients with liver diseases.
      In patients with collagen diseases or diabetes mellitus, the positive rate of
      ALP(5) was 40.4-66.7%. In conclusion, this method, in which HIALP is converted
      into ALP(5) by protease pretreatment and is separated from bone ALP, allows HIALP
      to be identified while other fractions remain unaffected.

PMID- 17506481
TI  - Evaluation of the Ortho-Clinical Diagnostics Vitros ECi Anti-HCV test: comparison
      with three other methods.
AB  - After observing a high incidence of low positive hepatitis C virus (HCV) antibody
      screens by the Ortho-Clinical Vitros ECi test (Orthoclinical Diagnostics,
      Raritan, NJ), we compared results against those obtained using another
      chemiluminescent analyzer, as well as two U.S. Food and Drug Administration (FDA)
      approved confirmatory methodologies. To ascertain the true anti-HCV status of
      samples deemed low-positive by the Ortho-Clinical Vitros ECi test, we tested
      samples using the ADVIA Centaur HCV screen test (Siemens Medical Solutions
      Diagnostics), the Chiron recombinant immunoblot assay (RIBA) test (Chiron Corp.,
      Emeryville, CA), and the Roche COBAS Amplicor HCV qualitative test (Roche
      Diagnostics, Indianapolis, IN) in a series of studies. Of 94 specimens positive
      by Vitros ECi, 19% were observed to be negative by Centaur. A separate study of
      91 samples with signal-to-cutoff (s/co) values less than 8.0 showed that all but
      one was negative for HCV ribonucleic acid (RNA). In comparison with RIBA, 100%
      (77) samples positive by the Vitros ECi test with s/co values less than 12.0 were
      negative or indeterminate by RIBA. A final study comparing all four methods side
      by-side showed 63% disagreement by Centaur for Vitros ECi low-positive samples,
      75% disagreement by RIBA, and 97% disagreement by polymerase chain reaction
      (PCR). In conclusion, the Ortho-Clinical Vitros ECi Anti-HCV test yields a high
      rate of false-positive results in the low s/co range in our patient population.

PMID- 17506482
TI  - Rapid detection of the UGT1A1 single nucleotide polymorphism G211A using real
      time PCR with Taqman minor groove binder probes.
AB  - The UGT1A1 Taqman MGB probe single nucleotide polymorphism (SNP) genotyping assay
      was developed to detect nucleotide 211 of the UDP-glucoronocyltransferase 1A1
      (UGT1A1) gene. Defects in this enzyme interfere with process of conjugation of
      bilirubin and cause unconjugated hyperbilirubinemia. Variation at nucleotide 211
      in the coding region of the UGT1A1 gene has been shown to be prevalent in
      Japanese and Chinese. Using an ABI sequence detection system (SDS) 7000, an
      allele-specific real-time PCR-based genotyping method was established to detect
      nucleotide G211A. Cord blood from 125 infants without hyperbilirubinemia
      (controls) were compared with cord blood from 74 infants (cases) with severe
      hyperbilirubinemia (total serum bilirubin > 300 micromol/L). Homozygous variation
      of the UGT1A1 gene at nucleotide 211(A/A) is significantly more common in cases
      (14.9%) than in controls (0.8%) (P<0.001). Direct sequencing from 20 randomly
      selected samples showed eight samples with homozygous wild type, seven with
      homozygous variant, and five samples were heterozygous. The result from this
      assay was in complete concordance with the DNA sequencing result and clearly
      discriminate wild-type (G/G), homozygous variant (A/A), and heterozygous (G/A).
      This assay is rapid and robust for screening of SNP G211A to determine if this
      polymorphism plays a role in causing severe neonatal jaundice in the local
      context.

PMID- 17506483
TI  - Elevation of CA 19-9 and chromogranin A, in addition to CA 125, are detectable in
      benign tumors in leiomyomas and endometriosis.
AB  - As the best-known tumor marker for ovarian carcinoma, CA 125 has also been
      commonly used to monitor patients with common benign gynecologic diseases such as
      endometriosis and leiomyoma. Both of these benign tumors are known to be at risk
      of developing into cancer. During the screening of an asymptomatic population
      with multiple tumor markers, including alpha-fetoprotein (AFP), carcinoembryonic
      antigen (CEA), prostate-specific antigen (PSA), CA 125, CA 19-9, CA 15-3,
      chromogranin A (CgA), and squamous cell carcinoma antigen (SCC), we have detected
      elevated tumor markers in 142 individuals; 19 of them were diagnosed with
      endometriosis or leiomyoma or both. In addition to the detection of elevation of
      CA 125 in these benign tumors, elevated CA 19-9 or CgA was also found in these
      patients with endometriosis or leiomyoma. Many patients only had elevated CA 19-9
      or CgA; the elevation of CA 125 was not detected. It appears that instead of
      monitoring only CA 125, as is traditionally done, multiple tumor markers,
      including CA 19-9, CgA, and CA 125, should be measured simultaneously in women
      with clinical disorders associated with the ovary or uterus in order to detect
      gynecologic benign tumors and in order to prevent further development of cancer.

PMID- 17506484
TI  - Relationship of serum adiponectin with blood lipids, HbA(1)c, and hs-CRP in type
      II diabetic postmenopausal women.
AB  - Adipose tissue has been considered an important endocrine organ. Adiponectin
      secretes from adipose tissue and plays an important role in the regulation of
      glycemia, beta-oxidation in muscle, and decreased insulin resistance in the
      liver. The objectives of this study were to compare the levels of adiponectin, hs
      C-reactive protein (CRP), HbA1c, and blood lipids among diabetic and healthy
      postmenopausal women, and to determine the relationship between circulating
      adiponectin and development of type II diabetes. This case-control study was
      performed on 28 diabetic and 42 age-matched healthy women. All participants were
      postmenopausal. Serum adiponectin concentrations, serum triglycerides (TG),
      cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density
      lipoprotein cholesterol (HDL-C) concentrations were determined. Blood HbA1c and
      serum hs-CRP were also measured. Adiponectin levels were significantly decreased
      (P<0.01) in the diabetic patients as compared to normal control subjects.
      Adiponectin levels were negatively associated with hs-CRP, LDL-C, HbA1c, TG, and
      total cholesterol (TC). A positive correlation was observed between adiponectin
      and HDL-C. The obtained data indicate that diabetic women have lower adiponectin
      levels compared to healthy women. HbA1c as an indicator of glycemic control has a
      negative correlation with serum adiponectin. Adiponectin may play an important
      role in the pathogenesis of diabetes, and may be an independent predictor of the
      development of diabetes in women.

PMID- 17506485
TI  - High-molecular intestinal alkaline phosphatase in chronic liver diseases.
AB  - The presence of high-molecular intestinal alkaline phosphatase (HIALP) different
      from bone ALP detected in the alpha(2)beta region was recently clarified. In this
      study we used a novel method in which HIALP was detected after conversion to
      ALP(5) by protease to investigate the clinical significance of the appearance of
      HIALP in patients with chronic liver disease. The subjects were 241 patients with
      chronic liver disease. When a decrease in ALP(3) in the alpha(2)beta region and
      an increase in ALP(5) in the beta region were noted, the patient was judged HIALP
      positive. In the patients with chronic liver disease, the total ALP activity (T
      ALP) increased with progression of the pathology in the order of chronic
      hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). HIALP
      appeared in 22.4% and 49.3% of patients with CH and LC, respectively, but the
      positivity rate decreased to 30.4% in HCC. As autoimmune liver diseases, primary
      biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) were investigated. T-ALP
      was lower in PBC+AIH than in LC and HCC, but the HIALP-positive rate was high
      (44.4%). The HIALP-positive rate was dependent on ABO blood groups, and was high
      in blood groups B and O. In conclusion, the HIALP-positive rate was particularly
      high in patients with chronic liver disease, and was related to the pathological
      progression, which suggests that the method is clinically useful.

PMID- 17506489
TI  - Tracing the genetic history of the Chinese people: mitochondrial DNA analysis of
      aneolithic population from the Lajia site.
AB  - Ancient DNA analysis was conducted on the dental remains of specimens from the
      Lajia site, dating back 3,800-4,000 years. The Lajia site is located in Minhe
      county, Qinghai province, in northwestern China. Archaeological studies link
      Lajia to the late period of the Qijia culture, one of the most important
      Neolithic civilizations of the upper Yellow River region, the cradle of Chinese
      civilization. Excavations at the site revealed that the inhabitants died in their
      houses as the result of a sudden flood. The Lajia site provides a rare chance to
      study the putative families, all of whom died at the same instant. Possible
      maternal familial relationships were investigated through mitochondrial DNA
      (mtDNA) sequence analysis. Twelve sequences from individuals found in one house
      were assigned to only five haplotypes, consistent with a possible close kinship.
      Results from analyses of RFLP typing and HVI motifs suggest that the Lajia people
      belonged to the haplogroups B, C, D, M*, and M10. This study, combined with
      archaeological and anthropological investigations, provides a better
      understanding of the genetic history of the Chinese people.

PMID- 17506490
TI  - Worldwide analysis of multiple microsatellites: language diversity has a
      detectable influence on DNA diversity.
AB  - Previous studies of the correlations between the languages spoken by human
      populations and the genes carried by the members of those populations have been
      limited by the small amount of genetic markers available and by approximations in
      the treatment of linguistic data. In this study we analyzed a large collection of
      polymorphic microsatellite loci (377), distributed on all autosomes, and used
      Ruhlen's linguistic classification, to investigate the relative roles of
      geography and language in shaping the distribution of human DNA diversity at a
      worldwide scale. For this purpose, we performed three different kinds of
      analysis: (i) we partitioned genetic variances at three hierarchical levels of
      population subdivision according to language group by means of a molecular
      analysis of variance (AMOVA); (ii) we quantified by a series of Mantel's tests
      the correlation between measures of genetic and linguistic differentiation; and
      (iii) we tested whether linguistic differences are increased across known zones
      of increased genetic change between populations. Genetic differences appear to
      more closely reflect geographic than linguistic differentiation. However, our
      analyses show that language differences also have a detectable effect on DNA
      diversity at the genomic level, above and beyond the effects of geographic
      distance.

PMID- 17506491
TI  - Trauma and violence in the Wari empire of the Peruvian Andes: warfare, raids, and
      ritual fights.
AB  - This study examines bioarchaeological evidence for violence during the period of
      Wari imperialism in the Peruvian Andes through analysis of skeletal trauma from
      three populations dating to AD 650-800. The samples are from contemporaneous
      archaeological sites: Conchopata, a Wari heartland site in central highland Peru;
      Beringa, a community of commoners in the Majes valley of the southern Wari
      hinterland; and La Real, a high status mortuary site, also in the Majes valley.
      Given the expansionist nature of Wari and its military-related iconography and
      weaponry, it is hypothesized that Wari imperialism was concomitant with greater
      levels of violence relative to other prehispanic groups in the Andes. It is also
      hypothesized that differential articulation with the Wari empire (e.g., heartland
      vs. hinterland groups) affected the frequency and patterning of trauma. Results
      show that cranial trauma frequency of the three Wari era samples is significantly
      greater than several other Andean skeletal populations. This suggests that Wari
      rule was associated with high levels of violence, though it may not have always
      been related to militarism. The three adult samples show similar frequencies of
      cranial trauma (Conchopata = 26%; Beringa = 33%; La Real = 31%). This may suggest
      that differential positioning in the Wari empire had little effect on exposure to
      violence. Sex-based differences in cranial trauma frequencies are present only at
      La Real, but wound patterning differs between the sexes: females display more
      wounds on the posterior of the cranium, while males show more on the anterior.
      These data suggest that Wari rule may have contributed to violence.

PMID- 17506492
TI  - Pseudo reaction kinetics of organic degradation products in dilute-acid-catalyzed
      corn stover pretreatment hydrolysates.
AB  - A variety of degradation products are produced upon pretreatment of
      lignocellulosic biomass with dilute acid. To date, the complexity of these
      samples has significantly limited the scope of efforts to perform summative
      analyses of degradation products. Qualitative and quantitative interrogation of
      hydrolysates is also paramount to identifying potential correlations between
      pretreatment chemistry and microbial inhibition in downstream bioconversion
      processes. A recently developed reversed-phase high performance liquid
      chromatography technique with UV detection has been applied to perform
      quantitative assessments of a variety of hydrolysate components as a function of
      pretreatment time and temperature. Correlations of product concentrations to the
      pretreatment severity function indicate differing responses of various compounds
      to the kinetic influences of temperature and reaction time. Of the compounds
      measured, four demonstrated initial accumulation rates were sufficiently linear
      over the time period tested to enable determination of activation energy E(a).
      All four compounds appear to demonstrate higher E(a) than that assumed in the
      commonly applied severity function. Overall accumulation trends for most
      compounds indicated similar under-estimation of apparent activation energy by the
      severity function. Biotechnol. Bioeng. 2007;98: 1135-1145. (c) 2007 Wiley
      Periodicals, Inc.

PMID- 17506493
TI  - Neurotrophic rationale in glaucoma: a TrkA agonist, but not NGF or a p75
      antagonist, protects retinal ganglion cells in vivo.
AB  - Glaucoma is a major cause of vision impairment, which arises from the sustained
      and progressive apoptosis of retinal ganglion cells (RGC), with ocular
      hypertension being a major risk or co-morbidity factor. Because RGC death often
      continues after normalization of ocular hypertension, growth factor-mediated
      protection of compromised neurons may be useful. However, the therapeutic use of
      nerve growth factor (NGF) has not proven effective at delaying RGC death in
      glaucoma. We postulated that one cause for the failure of NGF may be related to
      its binding to two receptors, TrkA and p75. These receptors have distinct
      cellular distribution in the retina and in neurons they induce complex and
      sometimes opposing activities. Here, we show in an in vivo therapeutic model of
      glaucoma that a selective agonist of the pro-survival TrkA receptor was effective
      at preventing RGC death. RGC loss was fully prevented by combining the selective
      agonist of TrkA with intraocular pressure-lowering drugs. In contrast, neither
      NGF nor an antagonist of the pro-apoptotic p75 receptor protected RGCs. These
      results further a neurotrophic rationale for glaucoma.

PMID- 17506494
TI  - Diminished climbing fiber innervation of Purkinje cells in the cerebellum of
      myosin Va mutant mice and rats.
AB  - Myosin Va is an actin-based molecular motor that is involved in organelle
      transport and membrane trafficking. Here, we explored the role of myosin Va in
      the formation of synaptic circuitry by examining climbing fiber (CF) innervation
      of Purkinje cells (PCs) in the cerebella of dilute-neurological (d-n) mice and
      dilute-opisthotonus (dop) rats that have mutations in dilute-encoded myosin Va.
      Anterograde labeling of CFs with biotinylated dextran amine (BDA) revealed that
      they arborized poorly and that their tips extended only half way through the
      thickness of the molecular layer (ML) in adult d-n mice. Using
      immunohistochemistry specific for vesicular glutamate transporter 2 (VGluT2) to
      visualize CF synaptic terminals, we found that during development and in
      adulthood, these terminals did not ascend as far along the proximal shaft
      dendrites of PCs in d-n mice and dop rats as they did in normal animals. An
      irregular distribution of BDA-labeled bulbous varicosities and VGluT2 spots along
      CF branches were also noted in these animals. Finally, VGluT2-positive CF
      terminals were occasionally localized on the PC somata of adult d-n cerebella.
      These phenotypes are consistent with our electrophysiological findings that CF
      mediated excitatory postsynaptic currents (EPSCs) were significantly smaller in
      amplitude and faster in decay in adult d-n mice, and that the regression of
      multiple CFs was slightly delayed in developing d-n mice. Taken together, our
      results suggest that myosin Va is essential for terminal CF extension and for the
      establishment of CF synapses within the proper dendritic territories of PCs.

PMID- 17506495
TI  - BDNF-mediated modulation of GABA and glycine release in dorsal horn lamina II
      from postnatal rats.
AB  - Recent studies show that excitatory glutamatergic transmission is potentiated by
      BDNF in superficial dorsal horn, both at the pre- and the postsynaptic site. The
      role of BDNF in modulating GABA and glycine-mediated inhibitory transmission has
      not been fully investigated. To determine whether the neurotrophin is effective
      in regulating the spontaneous release of the two neurotransmitters, we have
      recorded miniature inhibitory postsynaptic currents (mIPSCs) in lamina II of post
      natal rats. We show that application of BDNF enhanced the spontaneous release of
      GABA and glycine, in presence of tetrodotoxin. The effect was blocked by the trk
      receptor inhibitor k-252a. Amplitude and kinetics of mIPSCs were not altered.
      Evoked GABA and glycine IPSCs (eIPSCs) were depressed by BDNF and the coefficient
      of variation of eIPSC amplitude was significantly increased. By recording glycine
      eIPSCs with the paired-pulse protocol, an increase of paired-pulse ratio during
      BDNF application was observed. We performed parallel ultrastructural studies to
      unveil the circuitry involved in the effects of BDNF. These studies show that
      synaptic interactions between full length functional trkB receptors and GABA
      containing profiles only occur at non peptidergic synaptic glomeruli of types I
      and II. Expression of trkB in presynaptic vesicle-containing dendrites
      originating from GABAergic islet cells, indicates these profiles as key
      structures in the modulation of inhibitory neurotransmission by the neurotrophin.
      Our results thus describe a yet uncharacterized effect of BDNF in lamina II,
      giving further strength to the notion that the neurotrophin plays an important
      role in pain neurotransmission.

PMID- 17506496
TI  - The G-protein coupling properties of the human sweet and amino acid taste
      receptors.
AB  - The human T1R taste receptors are family C G-protein-coupled receptors (GPCRs)
      that act as heterodimers to mediate sweet (hT1R2 + hT1R3) and umami (hT1R1 +
      hT1R3) taste modalities. Each T1R has a large extracellular ligand-binding domain
      linked to a seven transmembrane-spanning core domain (7TMD). We demonstrate that
      the 7TMDs of hT1R1 and hT1R2 display robust ligand-independent constitutive
      activity, efficiently catalyzing the exchange of GDP for GTP on Galpha subunits.
      In contrast, relative to the 7TMDs of hT1R1 and hT1R2, the 7TMD of hT1R3 couples
      poorly to G-proteins, suggesting that in vivo signaling may proceed primarily
      through hT1R1 and hT1R2. In addition, we provide direct evidence that the hT1Rs
      selectively signal through Galpha(i/o) pathways, coupling to multiple Galpha(i/o)
      subunits as well as the taste cell specific Gbeta(1)gamma(13) dimer.

PMID- 17506497
TI  - Protein synthesis in distal axons is not required for axon growth in the
      embryonic spinal cord.
AB  - It is now well established that new proteins are synthesized in the distal
      segments of elongating axons, where they may play an essential role in some
      guidance decisions. It remains unclear, however, whether distal protein synthesis
      also plays an essential role in axon growth per se. Previous in vitro experiments
      have shown that blocking protein synthesis in distal axons has no effect on the
      rate of axonal advance. However, because these experiments were performed in
      vitro and over a relatively short time period, the role of distal protein
      synthesis over longer periods and in a native tissue environment remained
      untested. Here, we tested whether protein synthesis in distal axons plays an
      essential role in the elongation of descending axons in the embryonic spinal
      cord. We developed an in situ model of the brainstem-spinal projection of the
      embryonic chick, and developed a split-chamber method in which inhibitors of
      proteins synthesis could be applied independently to cell bodies in the brainstem
      or to distal axons in the spinal cord. When protein synthesis was blocked in
      distal axons, axon growth remained robust for 2 days, which is the length of the
      experiment. However, when protein synthesis was blocked only in the brainstem,
      axonal elongation in the spinal cord ceased within 6 h. These data showed that
      protein synthesis in the distal axon is not essential to continue the advance of
      axons. Rather, essential proteins are synthesized more proximally and then
      transported rapidly to the distal axon.

PMID- 17506498
TI  - Changes in cell migration and survival in the olfactory bulb of the pcd/pcd
      mouse.
AB  - Postnatally, the Purkinje cell degeneration mutant mice lose the main projecting
      neurons of the main olfactory bulb (OB): mitral cells (MC). In adult animals,
      progenitor cells from the rostral migratory stream (RMS) differentiate into
      bulbar interneurons that modulate MC activity. In the present work, we studied
      changes in proliferation, tangential migration, radial migration patterns, and
      the survival of these newly generated neurons in this neurodegeneration animal
      model. The animals were injected with bromodeoxyuridine 2 weeks or 2 months
      before killing in order to label neuroblast incorporation into the OB and to
      analyze the survival of these cells after differentiation, respectively. Both the
      organization and cellular composition of the RMS and the differentiation of the
      newly generated neurons in the OB were studied using specific markers of glial
      cells, neuroblasts, and mature neurons. No changes were observed in the cell
      proliferation rate nor in their tangential migration through the RMS, indicating
      that migrating neuroblasts are only weakly responsive to the alteration in their
      target region, the OB. However, the absence of MC does elicit differences in the
      final destination of the newly generated interneurons. Moreover, the loss of MC
      also produces changes in the survival of the newly generated interneurons, in
      accordance with the dramatic decrease in the number of synaptic targets
      available.

PMID- 17506500
TI  - Expression of FOS, EGR-1, and ARC in the amygdala and hippocampus of female rats
      during formation of the intromission mnemonic of pseudopregnancy.
AB  - Pseudopregnancy (PSP) in the female rat is a neuroendocrine condition that is
      induced by repeated and intermittent vaginocervical stimulation received during
      mating and involves the expression of bicircadian prolactin surges and cessation
      of normal estrous cyclicity for 10-12 days postmating. The temporal patterning
      and number of intromissions received by the female are critical for PSP
      initiation, and thus, short-term encoding of VCS occurs during transduction of
      intromissions into PSP. In this experiment, we characterized and compared the
      mating-induced neural activation patterns within amygdalar and hippocampal
      regions using expression of the immediate early genes FOS, EGR-1, and ARC.
      Cycling female rats mated on proestrus received 15 or 5 intromissions under paced
      or nonpaced mating conditions. High numbers of intromissions during nonpaced
      mating or low numbers received during paced mating are sufficient to induce PSP,
      while five nonpaced intromissions and mounts without intromission are
      insufficient. Here we demonstrate that the CA1 region of the hippocampus was
      selectively sensitive to PSP-sufficient but not PSP-insufficient mating
      stimulation by showing significant effects of paced mating for all three IEGs.
      Paced mating also stimulated the expression of ARC within the basolateral,
      cortical, and central nuclei of the amygdala. The posterodorsal medial amygdala
      also showed selective EGR-1 responses to PSP-sufficient mating stimulation. There
      was no effect of hemisphere on IEG expression. The postmating expression profiles
      of these IEGs provide evidence that limbic areas involved in encoding and
      consolidation of memory are involved in initiating the neuroendocrine memory of
      PSP.

PMID- 17506499
TI  - Mixed primary culture and clonal analysis provide evidence that NG2 proteoglycan
      expressing cells after spinal cord injury are glial progenitors.
AB  - NG2(+) cells in the adult rat spinal cord proliferate after spinal cord injury
      (SCI) and are postulated to differentiate into mature glia to replace some of
      those lost to injury. To further study these putative endogenous precursors,
      tissue at 3 days after SCI or from uninjured adults was dissociated, myelin
      partially removed and replicate cultures grown in serum-containing or serum-free
      medium with or without growth factors for up to 7 days in vitro (DIV). Cell yield
      after SCI was 5-6 times higher than from the normal adult. Most cells were
      OX42(+) microglia/macrophages but there were also more than twice the normal
      number of NG2(+) cells. Most of these coexpressed A2B5 or nestin, as would be
      expected for glial progenitors. Few cells initially expressed mature astrocyte
      (GFAP) or oligodendrocyte (CC1) markers, but more did at 7 DIV, suggesting
      differentiation of glial precursors in vitro. To test the hypothesis that NG2(+)
      cells after SCI express progenitor-like properties, we prepared free-floating
      sphere and single cell cultures from purified suspension of NG2(+) cells from
      injured spinal cord. We found that sphere cultures could be passaged in free
      floating subcultures, and upon attachment the spheres clonally derived from an
      acutely purified single cell differentiated into oligodendrocytes and rarely
      astrocytes. Taken together, these data support the hypothesis that SCI stimulates
      proliferation of NG2(+) cells that are glial progenitor cells. Better
      understanding the intrinsic properties of the NG2(+) cells stimulated by SCI may
      permit future therapeutic manipulations to improve recovery after SCI.

PMID- 17506501
TI  - DC electrical stimulation of the pretectal thalamus and its effects on the
      feeding behavior of the toad (Bufo bufo).
AB  - The feeding motivation of the common European common toad (Bufo bufo) can be
      quantified by the feeding sequence of arousal-orientation-approach-fixate-snap.
      Previous work has found that the optic tectum is an important structure
      responsible for the mediation of feeding behaviors, and combined electrical and
      visual stimulation of the optic tectum was found to increase the animals feeding
      behaviors. However, the pretectal thalamus has an inhibitory influence upon the
      optic tectum and its lesion results in disinhibited feeding behaviors. This
      suggests that feeding behavior of anurans is also subject to influence from the
      pretectal thalamus. Previous studies involving the application of DC stimulation
      to brain tissue has generated slow potential shifts and these shifts have been
      implicated in the modulation of the neural mechanisms associated with behavior.
      The current study investigated the application of DC stimulation to the
      diencephalon surface dorsal to the lateral posterodorsal pretectal thalamic
      nucleus in Bufo bufo, in order to assess effects on feeding motivation. The
      application of DC stimulation increased the incidence of avoidance behaviors to a
      visual prey stimulus while reducing the prey catching behavior component of
      approach, suggesting that the DC current applied to the pretectum increased the
      inhibition upon the feeding elements of the optic tectum. This can be explained
      by the generation of slow potential shifts.

PMID- 17506502
TI  - Interaction between hindbrain and spinal networks during the development of
      locomotion in zebrafish.
AB  - Little is known about the role of the hindbrain during development of spinal
      network activity. We set out to identify the activity patterns of reticulospinal
      (RS) neurons of the hindbrain in fictively swimming (paralyzed) zebrafish larvae.
      Simultaneous recordings of RS neurons and spinal motoneurons revealed that these
      were coactive during spontaneous fictive swim episodes. We characterized four
      types of RS activity patterns during fictive swimming: (i) a spontaneous pattern
      of discharges resembling evoked high-frequency spiking during startle responses
      to touch stimuli, (ii) a rhythmic pattern of excitatory postsynaptic potentials
      (EPSPs) whose frequency was similar to the motoneuron EPSP frequency during swim
      episodes, (iii) an arrhythmic pattern consisting of tonic firing throughout swim
      episodes, and (iv) RS cell activity uncorrelated with motoneuron activity.
      Despite lesions to the rostral spinal cord that prevented ascending spinal axons
      from entering the hindbrain (normally starting at approximately 20 h), RS neurons
      continued to display the aforementioned activity patterns at day 3. However,
      removal of the caudal portion of the hindbrain prior to the descent of RS axons
      left the spinal cord network unable to generate the rhythmic oscillations
      normally elicited by application of N-methyl-d-aspartate (NMDA), but in
      approximately 40% of cases chronic incubation in NMDA maintained rhythmic
      activity. We conclude that there is an autonomous embryonic hindbrain network
      that is necessary for proper development of the spinal central pattern generator,
      and that the hindbrain network can partially develop independently of ascending
      input.

PMID- 17506503
TI  - Extracellular ATP in activity-dependent remodeling of the neuromuscular junction.
AB  - Electrical activity during early development affects the development and
      maintenance of synapses (Spitzer [2006]: Nature 4447:707-712), but the
      intercellular signals regulating maintenance of synapses are not well identified.
      At the neuromuscular junction, adenosine 5-triphosphate (ATP) is coreleased with
      acetylcholine at activated nerve terminals to modulate synaptic function. Here we
      use cocultured mouse motor neurons and muscle cells in a three-compartment cell
      culture chamber to test whether endogenously released ATP plays a role in
      activity-dependent maintenance of neuromuscular synapses. The results suggest
      that ATP release at the synapse counters the negative effect of electrical
      activity, thus stabilizing activated synapses. Confirming our previous work (Li
      et al. [2001]: Nat Neurosci 4:871-872), we found that in doubly innervated
      muscles, electrical stimulation induced heterosynaptic downregulation of the
      nonstimulated convergent input to the muscle fiber with no or little change of
      the stimulated inputs. However, in preparations that were stimulated in the
      presence of apyrase, an enzyme that degrades extracellular ATP, synapse
      downregulation of stimulated inputs was substantial and significant, and end
      plate potentials were reduced. Apyrase treatment for 20 h in the absence of
      stimulation did result in moderate diminution, but this was prevented by blocking
      spontaneous neural activity with tetrodotoxin. The P2 receptor blocker, suramin,
      also induced activity-dependent synapse diminution. The decrease in synaptic
      efficacy produced by prolonged stimulation in the presence of apyrase persisted
      for greater than 20 h, consistent with a developmental time-course and distinct
      from the rapid neuromodulatory actions of ATP that have been demonstrated by
      others. We conclude that extracellular ATP promotes stabilization of the
      neuromuscular junction and may play a role in activity-dependent synaptic
      modification during development.

PMID- 17506504
TI  - Mechanical properties of femoral cortical bone following cemented hip
      replacement.
AB  - Femoral bone remodeling following total hip replacement is a big concern and has
      never been examined mechanically. In this study, six goats underwent unilateral
      cemented hip hemiarthroplasty with polymethyl methacrylate (PMMA) bone cement.
      Nine months later animals were sacrificed, and the femoral cortical bone slices
      at different levels were analysed using microhardness testing and microcomputed
      tomography (micro-CT) scanning. Implanted femurs were compared to contralateral
      nonimplanted femurs. Extensive bone remodeling was demonstrated at both the
      proximal and middle levels, but not at the distal level. Compared with the
      nonimplanted side, significant decreases were found in the implanted femur in
      cortical bone area, bone mineral density, and cortical bone hardness at the
      proximal level, as well as in bone mineral density and bone hardness at the
      middle level. However, no significant difference was observed in either variable
      for the distal level. In addition, similar proximal-to-distal gradient changes
      were revealed both in cortical bone microhardness and bone mineral density. From
      the mechanical point of view, the results of the present study suggested that
      stress shielding is an important mechanical factor associated with bone
      adaptation following total hip replacement.

PMID- 17506505
TI  - Locally delivered lovastatin nanoparticles enhance fracture healing in rats.
AB  - Statins stimulate bone formation in vitro and in vivo and, when given in large
      doses or by prolonged infusions, stimulate biomechanical strength of murine long
      bones with healing fractures. However, administration of statins by large oral
      doses or prolonged infusions to a fracture site is not a feasible therapeutic
      approach to hasten healing of human fractures. We administered lovastatin in
      biodegradable polymer nanobeads of poly(lactic-co-glycolide acid) to determine if
      lovastatin delivered in low doses in nanoparticles of a therapeutically
      acceptable scaffold could increase rates of healing in a standard preclinical
      model of femoral fracture. We found that these nanobeads: (1) stimulated bone
      formation in vitro at 5 ng/mL, (2) increased rates of healing in femoral
      fractures when administered as a single injection into the fracture site, and (3)
      decreased cortical fracture gap at 4 weeks as assessed by microcomputed
      tomography. These preclinical results suggest that lovastatin administered in a
      nanobead preparation may be therapeutically useful in hastening repair of human
      fractures.

PMID- 17506506
TI  - Decreased muscle loading delays maturation of the tendon enthesis during
      postnatal development.
AB  - Physical environment influences the development and maintenance of
      musculoskeletal tissues. The current study uses an animal model to explore the
      role of the physical environment on the postnatal development of the
      supraspinatus tendon enthesis. A supraspinatus intramuscular injection of
      botulinum toxin A was used to paralyze the left shoulders of mice at birth. The
      supraspinatus muscles of right shoulders were injected with saline to serve as
      contralateral controls. The supraspinatus enthesis was examined after 14, 21, 28,
      and 56 days of postnatal development. Histologic assays were used to examine
      fibrocartilage morphology and percentage osteoclast surface. Micro-computed
      tomography was used to examine muscle geometry and bone architecture. At 14 days
      there were no differences between groups in fibrocartilage formation, muscle
      geometry, bone architecture, or osteoclast surface. When comparing groups at 21,
      28, and 56 days, muscle volume was decreased, fibrocartilage development was
      delayed, mineralized bone was decreased, and osteoclast surface was higher at
      each timepoint in the botulinum group compared to the contralateral saline
      control group. Our results indicate that the development of the tendon enthesis
      is sensitive to its mechanical environment. A reduction in muscle loading delayed
      the development of the tendon-to-bone insertion site by impeding the accumulation
      of mineralized bone. Physical factors did not play a significant role in enthesis
      maturation in the first 14 days postnatally, implying that biologic factors may
      drive early postnatal development.

PMID- 17506507
TI  - Effects of OP-1 and PTH in a new experimental model for the study of metaphyseal
      bone healing.
AB  - The purpose of this study was to establish a reliable model of metaphyseal bone
      healing and to use this model to investigate the effect of recombinant human
      osteogenic protein 1 (rhOP-1; BMP-7) and parathyroid hormone fragment (PTH 1-34)
      on healing. A wedge-shaped osteotomy was created in the distal tibia of 16-week
      old female New Zealand White rabbits (n = 20) and was bridged with a custom-made
      external fixator. Five experimental groups of four animals each were
      investigated. In groups 1-4 the osteotomy gap was filled with tricalcium
      phosphate (TCP), and the gap was left unfilled in group 5 ("normal healing"). In
      group 1, 200 microg OP-1 was mixed in with the TCP. Groups 2 and 3 received daily
      subcutaneous injections of 10 and 40 microg/kg PTH, respectively, beginning on
      postoperative day 1. Radiographs were taken weekly. Following sacrifice on
      postoperative day 28, peripheral quantitative computed tomography (pQCT),
      histology, and mechanical testing (axial compression and torsion) were performed.
      Only one animal failed to complete the full 4-week time course, and no infections
      were encountered. Bone healing occurred in all animals. OP-1 stimulated bone
      formation locally, while the lower dose of PTH enhanced bone formation
      systemically (p < 0.05). Tibiae treated with OP-1 exhibited higher torsional
      strength (p = 0.04) than those in the normal healing group. These results
      indicate that a reliable and reproducible surgical model of metaphyseal healing
      has been established. In addition, differences in systemic versus local effects
      of PTH and OP-1 in accelerating metaphyseal fracture healing were found.

PMID- 17506508
TI  - Understanding the ergonomic risk for musculoskeletal disorders in the United
      States agricultural sector.
AB  - INTRODUCTION: Farming is a very large industry in the United States.
      Understanding the risks for injuries and more specifically musculoskeletal
      disorders in this industry poses a challenge for health officials. METHODS: A
      review was conducted of the existing peer-reviewed publications prior to December
      2006 about injuries and musculoskeletal disorders for farmers and farm workers.
      The aim was to review existing knowledge concerning: (1) the prevalence, types,
      and causes of farm-related injuries, paying particular attention to
      musculoskeletal disorders and the special populations within the agricultural
      sector, and (2) interventions that have been developed to reduce risk factors
      associated with farm-related injuries. RESULTS: Farmers and farm workers
      experience high rates of low back, shoulder, and upper extremity disorders.
      Musculoskeletal disorders may disproportionately affect farm youth and migrant
      workers due to the types of farm tasks performed. There is an urgent need for
      improved and validated interventions to reduce exposures and to improve the
      health of farmers and farm workers. DISCUSSION: Future farm-related
      musculoskeletal disorder research should emphasize: (1) better identification of
      exposures for special populations, (2) development of interventions for diverse
      farm populations, and (3) identification of additional exposures for
      musculoskeletal disorders. Inadequate understanding of musculoskeletal disorders
      in farming impedes efforts to prevent this common and important type of
      occupational injuries on farms.

PMID- 17506509
TI  - Utilization of a modified special-cubic design and an electronic tongue for
      bitterness masking formulation optimization.
AB  - A unique modification of simplex design was applied to an electronic tongue (E
      Tongue) analysis in bitterness masking formulation optimization. Three
      formulation variables were evaluated in the simplex design, i.e. concentrations
      of two taste masking polymers, Amberlite and Carbopol, and pH of the granulating
      fluid. Response of the design was a bitterness distance measured using an E
      Tongue by applying a principle component analysis, which represents taste masking
      efficiency of the formulation. The smaller the distance, the better the
      bitterness masking effect. Contour plots and polynomial equations of the
      bitterness distance response were generated as a function of formulation
      composition and pH. It was found that interactions between polymer and pH reduced
      the bitterness of the formulation, attributed to pH-dependent ionization and
      complexation properties of the ionic polymers, thus keeping the drug out of
      solution and unavailable to bitterness perception. At pH 4.9 and an
      Amberlite/Carbopol ratio of 1.4:1 (w/w), the optimal taste masking formulation
      was achieved and in agreement with human gustatory sensation study results.
      Therefore, adopting a modified simplex experimental design on response measured
      using an E-Tongue provided an efficient approach to taste masking formulation
      optimization using ionic binding polymers.

PMID- 17506510
TI  - Onion phases of PEG-8 distearate.
AB  - The aims of the present study were to formulate stable onion phases of the
      biodegradable surfactant PEG-8 Distearate (PEG8DS) and evaluate application of
      the onion phases in encapsulating sumatriptan succinate, a BCS class III potent
      antimigraine drug. Drug loaded and placebo onion phases were prepared by shearing
      lyotropic lamellar phases of the surfactant. Effect of drug/surfactant ratio,
      shear rate and shear time on particle size, and encapsulation efficiency were
      studied. The onion phases were characterized by polarized microscopy, small angle
      neutron scattering (SANS), NMR, rheology, and FTIR. Formation of onion phases of
      PEG8DS was confirmed by the presence of maltese crosses under a crosspolarized
      microscope and further by SANS studies. The onion phases revealed an increase of
      inter-bilayer spacing by 7 A after drug incorporation. NMR studies revealed
      location of drug in the aqueous phases of the multilamellar vesicles (MLVs). FTIR
      study revealed no interaction between drug and surfactant. Drug loaded onion
      phases exhibited high encapsulation efficiency ( approximately 90%) and rapid in
      vitro drug release (>90% in 10 min). Onion phases stored at 5 degrees C +/- 3
      degrees C revealed no significant drug leakage at the end of 3 months suggesting
      adequate stability. Sumatriptan succinate loaded stable onion phases of PEG8DS
      with high entrapment efficiency and rapid drug release suggests potential
      application of the onion phases in drug delivery.

PMID- 17506511
TI  - Study of the individual contributions of ice formation and freeze-concentration
      on isothermal stability of lactate dehydrogenase during freezing.
AB  - The objective of this study was to determine the individual contributions of ice
      formation, solute concentration, temperature, and time, to irreversible protein
      denaturation during freezing. A temperature-step approach was used to study
      isothermal degradation of frozen lactate dehydrogenase (LDH). The freeze
      concentrate composition was determined using differential scanning calorimetry to
      enable preparation of solutions, without ice, of the same concentration as the
      freeze-concentrate, and thereby determine the role of the freeze-concentrate
      composition on LDH degradation. Both stabilizers employed in the study,
      hydroxyethyl starch and sucrose, conferred cryoprotection on LDH. While LDH
      stability was lower at 1.50-3.25% w/v sucrose than in the absence of sucrose,
      cryoprotection was restored at higher sucrose concentrations. pH shift during
      freezing, degree of supercooling, and excipient impurities were ruled out as
      causes for unusual LDH stability behavior at lower sucrose concentrations.
      Specific surface area measurements of the freeze-dried cakes showed that the ice
      surface area increased with an increase in sucrose concentration. No LDH
      degradation occurred in concentrated solutions, without ice, at the same
      composition as the freeze-concentrate in frozen systems where massive degradation
      was documented. Thus, ice formation is the critical destabilizing factor during
      freezing of LDH in sucrose:citrate buffer systems.

PMID- 17506512
TI  - Reverse iontophoresis of L-lactate: in vitro and in vivo studies.
AB  - This work investigates the reverse iontophoretic extraction of lactate, a widely
      used marker of tissue distress in critically ill patients and of sports
      performance. In vitro experiments were performed to establish the relationship
      between subdermal lactate levels and lactate iontophoretic extraction fluxes.
      Subsequently, the iontophoretic extraction of lactate was performed in vivo in
      healthy volunteers. Lactate was quickly and easily extracted by iontophoresis
      both in vitro and in vivo. During a short initial phase, iontophoresis extracts
      the lactate present in the skin reservoir, providing information of relevance,
      perhaps, for dermatological and cosmetic applications. In a second step, lactate
      is extracted from the interstitial subdermal fluid allowing local lactate
      kinetics to be followed in a completely non-invasive way. The simultaneous in
      vivo extraction of chloride, and its possible role as an internal standard to
      calibrate lactate reverse iontophoretic fluxes, was also demonstrated. Despite
      these positive findings, however, considerably more research is necessary to
      eliminate potential artefacts and to facilitate interpretation of the data.

PMID- 17506513
TI  - Transient acid exposure increases sevelamer HCl phosphate binding.
AB  - The patient-to-patient variability in the dosing of sevelamer HCl for phosphate
      control led us to test whether the binder's transient exposure to acidic
      environments (such as the stomach) might alter the compound so as to change its
      subsequent binding capacity in the more alkaline small intestine. We hypothesized
      that an acid milieu could either increase the reactive sites (protonated amine
      groups) or make the polymer more hydrophilic (hydration and swelling allowing
      more phosphate to reach those sites). Eight hundred milligrams of Renagel tablets
      were exposed to pHs 1, 2.3, and 7 (n = 7 each acidity level) for 1 h. NaCl was
      added to keep ionic strength the same. Measured by atomic emission phosphate
      uptake after 3 h at pH 7 was, respectively, 3.13 +/- 0.21, 2.72 +/- 0.35, and
      1.85 +/- 0.46 mequiv./g (p = 0.0006, pH 1 vs. pH 7). Semi-automated computerized
      image analysis was then performed to measure swelling of the particles. We
      constructed a glass continuous-flow cell that allowed stationary particles and
      real-time photography. Using digitized optical measurements there was no
      difference (p > 0.8) between the swelling after 1 h of pH 1 or 7 solutions (60.2
      +/- 14.8% vs. 59.5 +/- 9.8% increase in diameter). Our findings support the
      importance of transient acid exposure in enhancing phosphate binding, due to
      increased protonated sites rather than by more swelling. Patients with acquired
      or pharmacologic achlorhydria would not benefit from this unexpected in vivo
      reaction. Possibly manufacturing sevelamer with a higher degree of protonation or
      administering it with appropriately acidic vehicles or beverages remains to be
      investigated.

PMID- 17506514
TI  - Investigation of the influence of particle size on the excipient percolation
      thresholds of HPMC hydrophilic matrix tablets.
AB  - In previous papers of our research group, a linear relationship between the drug
      percolation threshold and the relative drug particle size (drug/excipient) has
      been found, in the case of the inert matrices. The objective of the present paper
      is to investigate the influence of the particle size on the excipient percolation
      threshold in the case of hydrophilic matrices. This influence can have important
      consequences on the release behaviour of these controlled release devices. Matrix
      tablets have been prepared using KCl/Lobenzarit Disodium as drugs and HPMC K4M as
      matrix forming material, employing six different excipient/drug particle size
      ratios (ranging from 0.42 to 4.16). The formulations studied contain a drug
      loading in the range of 20-90% (w/w). In order to estimate the percolation
      threshold, the behaviour of the kinetic parameters with respect to the volumetric
      fraction of each component at time zero, was studied. The obtained results
      support the existence of a linear relationship between a component percolation
      threshold (drug or excipient) and its relative particle size (drug/excipient in
      the case of the drug percolation threshold or excipient/drug in the case of the
      excipient percolation threshold). This relationship is valid for different drugs,
      excipients and systems (inert or hydrophilic matrix tablets).

PMID- 17506515
TI  - Enhancing absorption of fluorescein and LHRH across hindgut epithelia in a
      marsupial, the common brushtail possum Trichosurus vulpecula.
AB  - We have identified differences in transport properties of intestinal epithelia in
      the marsupial brushtail possum, compared to eutherian mammals. To determine
      whether differences in its permeability to hydrophilic compounds also occur, the
      absorption of sodium fluorescein and luteinizing hormone releasing hormone (LHRH)
      was assessed in vitro and the ability of chemical enhancers and a metabolic
      inhibitor to promote their absorption investigated. The apparent permeability of
      colonic and caecal tissues to fluorescein and LHRH and transepithelial resistance
      (Rt) in the absence or presence of ethylenediamine tetra-acetic acid (EDTA),
      sodium deoxycholic acid (SDA), dithiothreitol (DTT), polyacrylic acids (PAA), or
      the inhibitor bacitracin were determined. The effects of SDA and/or DTT on
      adherent mucus and the release of lactate dehydrogenase (LDH) were also assessed.
      In the absence of treatment, both tissues had comparable amounts of adherent
      mucus, Rt and low permeabilities to fluorescein and LHRH. All chemical enhancers
      increased fluorescein permeability, but SDA at concentrations >0.5 mM also
      induced LDH release. DTT alone and in combination with SDA reduced the amount of
      adherent mucus. Bacitracin inhibited LHRH metabolism and increased LHRH
      permeability. These data indicate that the possum hindgut epithelium represents a
      significant barrier to the uptake of hydrophilic compounds, similar to that in
      eutherians.

PMID- 17506516
TI  - The chemical versatility of natural-product assembly lines.
AB  - Microbial natural products of both polyketide and nonribosomal peptide origin
      have been and continue to be important therapeutic agents as antibiotics,
      immunosupressants, and antitumor drugs. Because the biosynthetic genes for these
      metabolites are clustered for coordinate regulation, the sequencing of bacterial
      genomes continues to reveal unanticipated biosynthetic capacity for novel natural
      products. The re-engineering of pathways for such secondary metabolites to make
      novel molecular variants will be enabled by understanding of the chemical logic
      and protein machinery in the producer microbes. This Account analyzes the
      chemical principles and molecular logic that allows simple primary metabolite
      building blocks to be converted to complex architectural scaffolds of polyketides
      (PK), nonribosomal peptides (NRP), and NRP-PK hybrids. The first guiding
      principle is that PK and NRP chains are assembled as thioseters tethered to
      phosphopantetheinyl arms of carrier proteins that serve as thiotemplates for
      chain elongation. The second principle is that gate keeper protein domains select
      distinct monomers to be activated and incorporated with positional specificity
      into the growing natural product chains. Chain growth is via thioclaisen
      condensations for PK and via amide bond formation for elongating NRP chains.
      Release of the full length acyl/peptidyl chains is mediated by thioesterases,
      some of which catalyze hydrolysis while others catalyze regiospecific
      macrocyclization to build in conformational constraints. Tailoring of PK and NRP
      chains, by acylation, alkylation, glycosylation, and oxidoreduction, occurs both
      during tethered chain growth and after thioesterase-mediated release. Analysis of
      the types of protein domains that carry out chain initiation, elongation,
      tailoring, and termination steps gives insight into how NRP and PK biosynthetic
      assembly lines can be redirected to make novel molecules.

PMID- 17506517
TI  - Developing chiral ligands for asymmetric hydrogenation.
AB  - This Account outlines our efforts in ligand development for asymmetric
      hydrogenation. The successful development of three classes of ligands is
      presented, including (1) ligands with phosphocyclic motifs, (2) ligands with
      atropisomeric backbones, and (3) bisphosphine ligands inspired by the structure
      of 2,3- O-isopropylidene-2,3-dihydroxyl-1,4-bis(diphenylphosphino)butane (DIOP).
      With this large ligand toolbox, we have prepared many pharmaceutically valuable
      chiral products efficiently.

PMID- 17506518
TI  - Quantitative high-throughput screening of osteoblast attachment, spreading, and
      proliferation on demixed polymer blend micropatterns.
AB  - Designing materials that regulate cell function in a desired manner is a major
      goal of biomaterials engineering. Challenges include the vast material property
      space to be explored, the complexity of cell-surface interactions, and the
      empirical nature of research in this field. To address these challenges,
      combinatorial methods have been developed in recent years for screening cell
      responses to material surfaces. Previous work using gradient libraries of
      biodegradable polymers poly(epsilon-caprolactone) and poly(D,L-lactide) showed
      qualitatively that alkaline phosphatase activity of MC3T3-E1 osteoblasts was
      dramatically enhanced at specific blend compositions and temperatures. In this
      study, we expand the combinatorial screening to measure quantitatively early
      events in the osteoblast life cycle: attachment, spreading, and proliferation. In
      addition, this work relates these cell assays to quantitative measures of polymer
      surface microstructure and topography. In general, cell attachment was favored on
      the more hydrophilic PDLA domains. However, cell spreading was strongly
      influenced by phase-separated microstructures on the polymer surfaces. Regions of
      enhanced cell proliferation shifted from one microstructural region to others as
      the culture progressed from 3 to 8 days. Viability showed no response to the
      surface features of the libraries. These screening results indicate the precise
      preparatory conditions and microstructure/topography ranges that should be used
      to design future confirmatory studies of the fundamental mechanisms of cell
      response to these heterogeneous patterned surfaces. Given the complex nature and
      breadth of these parameters, the simplification of the parameter space to be
      explored is an important advance.

PMID- 17506519
TI  - Amphiphilic N-glycosyl-thiocarbamoyl cyclodextrins: synthesis, self-assembly, and
      fluorimetry of recognition by Lens culinaris lectin.
AB  - Amphiphilic beta-cyclodextrins have been synthesized bearing hexylthio,
      dodecylthio, and hexadecylthio chains at the 6-positions and
      glycosylthiocarbamoyl-oligo(ethylene glycol) units at the 2-positions. The
      glycosyl residues (alpha-D-mannosyl and beta-L-fucosyl) are intended for cell
      targeting. Self-assembly of these new amphiphilic glycosylated cyclodextrins in
      water to form vesicles was investigated by dynamic light scattering and
      transmission electron microscopy. Selective binding of the hexylthio assemblies
      to a protein receptor (Lens culinaris lectin) was confirmed by fluorescence
      spectroscopy.

PMID- 17506521
TI  - Method for quantifying the PEGylation of gelatin nanoparticle drug carrier
      systems using asymmetrical flow field-flow fractionation and refractive index
      detection.
AB  - The PEGylation of colloidal drug carrier systems protects them from a rapid
      clearance from the blood stream and therefore prolongs their plasma half-lives.
      This fundamental concept is nowadays widely applied whereas the analytical
      description, i.e., the quantification of the PEGylation process, is still
      challenging due to the poor spectrophotometrical properties of PEG. The aim of
      this work is to quantify the PEGylation process of gelatin nanoparticles by
      utilizing the combination of asymmetrical flow field-flow fractionation (AF4) and
      refractive index (RI) detection and to demonstrate the potential of AF4 in the
      work with colloidal drug carrier systems. An AF4 separation mechanism of gelatin
      nanoparticles and PEG was developed without further sample preparation. After
      separation, the PEGylation could be directly quantified from the respective RI
      data and a threshold of a maximum amount of PEG that can be bound onto the
      surface of the nanoparticles could be determined. The PEGylation could be further
      visualized by atomic force microscopy (AFM). In sum, the presented results show
      the successful application of AF4 in the field of colloidal drug carrier systems,
      and in combination with AFM, both techniques can be stated as promising tools for
      the future analysis of colloidal drug carrier systems.

PMID- 17506520
TI  - Enhanced bacterial protein expression during auto-induction obtained by
      alteration of lac repressor dosage and medium composition.
AB  - The auto-induction method of protein expression in E. coli is based on diauxic
      growth resulting from dynamic function of lac operon regulatory elements (lacO
      and LacI) in mixtures of glucose, glycerol, and lactose. The results show that
      successful execution of auto-induction is strongly dependent on the plasmid
      promoter and repressor construction, on the oxygenation state of the culture, and
      on the composition of the auto-induction medium. Thus expression hosts expressing
      high levels of LacI during aerobic growth exhibit reduced ability to effectively
      complete the auto-induction process. Manipulation of the promoter to decrease the
      expression of LacI altered the preference for lactose consumption in a manner
      that led to increased protein expression and partially relieved the sensitivity
      of the auto-induction process to the oxygenation state of the culture. Factorial
      design methods were used to optimize the chemically defined growth medium used
      for expression of two model proteins, Photinus luciferase and enhanced green
      fluorescent protein, including variations for production of both unlabeled and
      selenomethionine-labeled samples. The optimization included studies of the
      expression from T7 and T7-lacI promoter plasmids and from T5 phage promoter
      plasmids expressing two levels of LacI. Upon the basis of the analysis of over
      500 independent expression results, combinations of optimized expression media
      and expression plasmids that gave protein yields of greater than 1000 mug/mL of
      expression culture were identified.

PMID- 17506522
TI  - Loss of bonded phase in reversed-phase liquid chromatography in acidic eluents
      and practical ways to improve column stability.
AB  - Silica-based, reversed-phase liquid chromatographic (RPLC) stationary phases are
      very widely used to separate basic compounds in acidic eluents due to their high
      efficiency, good mechanical strength, and the versatile selectivity offered by
      different functional groups and the chemistry on the silica surface. However, the
      stability in acid of most silica-based stationary phases is poor, especially at
      elevated temperatures, due to hydrolysis of the siloxane bonds, which hold
      silanes on the silica substrate. This hydrolysis is commonly believed to be
      solely the result of catalysis by protons. However, we show that various metal
      cations (principally Fe3+/Fe2+, Ni2+, and Cr3+) released from acid corrosion of
      the stainless steel inlet frit greatly accelerate the hydrolysis of the siloxane
      bond. Furthermore, these metal cations, and not the high acidity per se, are
      mainly responsible for column instability. We show that removing the stainless
      steel inlet frit, or use of a titanium frit, greatly reduces or totally
      eliminates corrosion of the inlet frit and radically improves retention
      stability. The effects of various acids and types of organic modifier were also
      studied. These observations suggest a number of practical approaches that can
      significantly extend the lifetime of any RPLC stationary phase in acidic media at
      elevated temperature.

PMID- 17506523
TI  - Advanced multiple-angle incidence resolution spectrometry for thin-layer analysis
      on a low-refractive-index substrate.
AB  - A long-time issue that thin films supported on a substrate with low refractive
      index cannot be subjected to multiple-angle incidence resolution spectrometry
      (MAIRS) has been resolved, and an advanced MAIRS technique has been developed.
      Infrared multiple-angle incidence resolution spectroscopy (IR MAIRS) is being
      recognized as a powerful spectroscopic tool for revealing molecular orientation
      in thin films or molecular adsorbates. MAIRS has been, however, employed with
      only IR spectroscopy thus far, since MAIRS requires high refractive index
      substrates such as germanium and silicon, and shorter wavelength regions have no
      appropriate substrates. Although one of the most commonly useful substrates for
      IR spectroscopy is CaF2, unfortunately it cannot be employed for IR MAIRS because
      of the low refractive index. To overcome this experimental limitation, the
      principle of MAIRS has been studied theoretically, and it has been found that
      polarization effects on transmission intensity is the main cause that disturbs a
      proper MAIRS analysis. As a result, now it is possible to employ IR MAIRS for
      analysis of thin films on CaF2 by removing the s-polarization and by use of the
      advanced MAIRS algorithm.

PMID- 17506524
TI  - Forensic science.

PMID- 17506525
TI  - Formation and properties of [4Fe-4S] clusters on the IscU scaffold protein.
AB  - Rapid and quantitative reductive coupling of two [2Fe-2S]2+ clusters to form a
      single [4Fe-4S]2+ cluster on the homodimeric IscU Fe-S cluster scaffold protein
      has been demonstrated by UV-visible absorption, Mossbauer, and resonance Raman
      spectroscopies, using dithionite as the electron donor. Partial reductive
      coupling was also observed using reduced Isc ferredoxin, which raises the
      possibility that Isc ferredoxin is the physiological reductant. The results
      suggest that reductive coupling of adjacent [2Fe-2S]2+ clusters assembled on IscU
      provides a general mechanism for the final step in the biosynthesis of [4Fe-4S]2+
      clusters. The [4Fe-4S]2+ center on IscU can be reduced to a S = 1/2[4Fe-4S]+
      cluster (g parallel = 2.06 and g perpendicular = 1.92), but the low midpoint
      potential (< -570 mV) and instability of the reduced cluster argue against any
      physiological relevance for the reduced cluster. On exposure to O2, the [4Fe
      4S]2+ cluster on IscU degrades via a semistable [2Fe-2S]2+ cluster with
      properties analogous to those of the [2Fe-2S]2+ center in [2Fe-2S]2+ IscU. It is
      suggested that the ability of IscU to accommodate either [2Fe-2S]2+ or [4Fe-4S]2+
      clusters in response to cellular redox status and/or oxygen levels may provide an
      effective way to populate appropriately cluster-loaded forms of IscU for
      maturation of different types of [Fe-S] proteins.

PMID- 17506526
TI  - In vitro activation of apo-aconitase using a [4Fe-4S] cluster-loaded form of the
      IscU [Fe-S] cluster scaffolding protein.
AB  - Genetic experiments have established that IscU is involved in maturation of [Fe
      S] proteins that require either [2Fe-2S] or [4Fe-4S] clusters for their
      biological activities. Biochemical studies have also shown that one [2Fe-2S]
      cluster can be assembled in vitro within each subunit of the IscU homodimer and
      that these clusters can be reductively coupled to form a single [4Fe-4S] cluster.
      In the present work, it is shown that the [4Fe-4S] cluster-loaded form of A.
      vinelandii IscU, but not the [2Fe-2S] cluster-loaded form, can be used for intact
      cluster transfer to an apo form of A. vinelandii aconitase A, a member of the
      monomeric dehydratase family of proteins that requires a [4Fe-4S] cluster for
      enzymatic activity. The rate of [4Fe-4S] cluster transfer from IscU to apo
      aconitase A was not affected by the presence of the HscA/HscB co-chaperone system
      and MgATP. However, an altered form of a [4Fe-4S] cluster-containing IscU, having
      the highly conserved aspartate-39 residue substituted with alanine, is an
      effective inhibitor of wild-type [4Fe-4S] cluster-loaded IscU-directed activation
      of apo-aconitase A. In contrast, neither the clusterless form of IscU nor the
      [2Fe-2S] cluster-loaded form of IscU is an effective inhibitor of IscU-directed
      apo-aconitase A activation. These results are interpreted to indicate that the
      [2Fe-2S] and [4Fe-4S] cluster-loaded forms of IscU adopt different conformations
      that provide specificity with respect to the maturation of [2Fe-2S] and [4Fe-4S]
      centers in proteins.

PMID- 17506527
TI  - Exhaustive mutagenesis of six secondary active-site residues in Escherichia coli
      chorismate mutase shows the importance of hydrophobic side chains and a helix N
      capping position for stability and catalysis.
AB  - Secondary active-site residues in enzymes, including hydrophobic amino acids, may
      contribute to catalysis through critical interactions that position the reacting
      molecule, organize hydrogen-bonding residues, and define the electrostatic
      environment of the active site. To ascertain the tolerance of an important model
      enzyme to mutation of active-site residues that do not directly hydrogen bond
      with the reacting molecule, all 19 possible amino acid substitutions were
      investigated in six positions of the engineered chorismate mutase domain of the
      Escherichia coli chorismate mutase-prephenate dehydratase. The six secondary
      active-site residues were selected to clarify results of a previous test of
      computational enzyme design procedures. Five of the positions encode hydrophobic
      side chains in the wild-type enzyme, and one forms a helix N-capping interaction
      as well as a salt bridge with a catalytically essential residue. Each mutant was
      evaluated for its ability to complement an auxotrophic chorismate mutase deletion
      strain. Kinetic parameters and thermal stabilities were measured for variants
      with in vivo activity. Altogether, we find that the enzyme tolerated 34% of the
      114 possible substitutions, with a few mutations leading to increases in the
      catalytic efficiency of the enzyme. The results show the importance of secondary
      amino acid residues in determining enzymatic activity, and they point to
      strengths and weaknesses in current computational enzyme design procedures.

PMID- 17506528
TI  - Effect of the N-terminus on heme cavity structure, ligand equilibrium, rate
      constants, and reduction potentials of nitrophorin 2 from Rhodnius prolixus.
AB  - The D1A mutant of recombinant NP2 has been prepared and shown to have the
      expression-initiation methionine-0 cleaved during expression in E. coli, as is
      the case for recombinant NP4, where Ala is the first amino acid for the
      recombinant protein as well as for the mature native protein. The heme
      substituent 1H NMR chemical shifts of NP2-D1A and those of its imidazole, N
      methylimidazole, and cyanide complexes are rather different from those of NP2
      M0D1. This difference is likely due to the much smaller size of the N-terminal
      amino acid (A) of NP2-D1A, which allows the formation of the closed loop form of
      this protein, as it does for NP4 (Weichsel, A., Andersen, J. F., Roberts, S. A.,
      and Montfort, W. R. (2000) Nature Struct. Biol. 7, 551-554). The ratio of the two
      hemin rotational isomers A and B is different for the two proteins, and the rate
      at which the A:B ratio reaches equilibrium is strikingly different (NP2-M0D1 t1/2
      for heme rotation approximately 2 h, NP2-D1A t1/2 approximately 43 h). This
      difference is consistent with the high stability of the closed loop form of the
      NP2-D1A protein and infrequent opening of the loops that could allow heme to at
      least partially exit the binding pocket in order to rotate about its alpha,gamma
      meso axis. Consistent with this, the rates of histamine binding and release
      to/from NP2-D1A are significantly slower than those for NP2-M0D1 at pH 7.5. This
      work suggests that care must be taken in interpreting data obtained from proteins
      that carry the expression-initiation M0.

PMID- 17506530
TI  - Sequence context- and temperature-dependent nucleotide excision repair of a
      benzo[a]pyrene diol epoxide-guanine DNA adduct catalyzed by thermophilic UvrABC
      proteins.
AB  - The influence of DNA base sequence context on the removal of a bulky
      benzo[a]pyrene diol epoxide-guanine adduct, (+)-trans-B[a]P-N2-dG (G*), by UvrABC
      nuclease from the thermophilic organism Bacillus caldotenax was investigated. The
      lesion was flanked by either T or C in otherwise identical complementary 43-mer
      duplexes (TG*T or CG*C, respectively). It was reported earlier that in the CG*C
      context, a dominant minor groove adduct structure was observed by NMR methods
      with all Watson-Crick base pairs intact, and the duplex exhibited a rigid bend.
      In contrast, in the TG*T context, a highly flexible bend was observed, base
      pairing at G*, and two 5'-base pairs flanking the adduct were impaired, and
      multiple solvent-accessible adduct conformations were observed. The TG*T-43-mer
      duplexes are incised with consistently greater efficiency by UvrABC proteins from
      B. caldotenax by a factor of 2.3 +/- 0.3. The rates of incisions increase with
      increasing temperature and are characterized by linear Arrhenius plots with
      activation energies of 27.0 +/- 1.5 and 23.4 +/- 1.0 kcal/mol for CG*C and TG*T
      duplexes, respectively. These values reflect the thermophilic characteristics of
      the UVrABC nuclease complex and the contributions of the different DNA substrates
      to the overall activation energies. These effects are consistent with base
      sequence context-dependent differences in structural disorder engendered by a
      loss of local base stacking interactions and Watson-Crick base pairing in the
      immediate vicinity of the lesions in the TG*T duplexes. The local weakening of
      base pairing interactions constitutes a recognition element of the UvrABC
      nucleotide excision repair apparatus.

PMID- 17506531
TI  - Caught after the Act: a human A-type metallocarboxypeptidase in a product complex
      with a cleaved hexapeptide.
AB  - A/B-type metallocarboxypeptidases (MCPs) are among the most thoroughly studied
      proteolytic enzymes, and their catalytic mechanisms have been considered as
      prototypes even for several unrelated metalloprote(in)ase families. It has long
      been postulated that the nature of the side chains of at least five substrate
      residues, i.e., P4-P1', influence Km and kcat and that once the peptide or
      protein substrate is cleaved, both products remain in the first instance bound to
      the active-site cleft of the enzyme in a double-product complex. Structural
      details of binding of substrate to the nonprimed side of the cleft have largely
      relied on complexes with protein inhibitors and peptidomimetic small-molecule
      inhibitors that do not span the entire groove. In the former, the presence of N
      terminal globular protein domains participating in large-scale interactions with
      the surface of the cognate catalytic domain outside the active-site cleft mostly
      conditions the way their C-terminal tails bind to the cleft. Accordingly, they
      may not be accurate models for a product complex. We hereby provide the
      structural details of a true cleaved double-product complex with a hexapeptide of
      an MCP engaged in prostate cancer, human carboxypeptidase A4, employing
      diffraction data to 1.6 A resolution (Rcryst and Rfree = 0.159 and 0.176,
      respectively). These studies provide detailed information about subsites S5-S1'
      and contribute to our knowledge of the cleavage mechanism, which is revisited in
      light of these new structural insights.

PMID- 17506529
TI  - Unusually strong binding to the DNA minor groove by a highly twisted
      benzimidazole diphenylether: induced fit and bound water.
AB  - RT29 is a dicationic diamidine derivative that does not obey the classical
      "rules" for shape and functional group placement that are expected to result in
      strong binding and specific recognition of the DNA minor groove. The compound
      contains a benzimidazole diphenyl ether core that is flanked by the amidine
      cations. The diphenyl ether is highly twisted and gives the entire compound too
      much curvature to fit well to the shape of the minor groove. DNase I
      footprinting, fluorescence intercalator displacement studies, and circular
      dichroism spectra, however, indicate that the compound is an AT specific minor
      groove binding agent. Even more surprisingly, quantitative biosensor-surface
      plasmon resonance and isothermal titration calorimetric results indicate that the
      compound binds with exceptional strength to certain AT sequences in DNA with a
      large negative enthalpy of binding. Crystallographic results for the DNA complex
      of RT29 compared to calculated results for the free compound show that the
      compound undergoes significant conformational changes to enhance its minor groove
      interactions. In addition, a water molecule is incorporated directly into the
      complex to complete the compound-DNA interface, and it forms an essential link
      between the compound and base pair edges at the floor of the minor groove. The
      calculated DeltaCp value for complex formation is substantially less than the
      experimentally observed value, which supports the idea of water being an
      intrinsic part of the complex with a major contribution to the DeltaCp value.
      Both the induced fit conformational changes of the compound and the bound water
      are essential for strong binding to DNA by RT29.

PMID- 17506532
TI  - Structure modeling of trivalent lanthanum and lutetium complexes: Sparkle/PM3.
AB  - The recently defined Sparkle model for the quantum chemical prediction of
      geometries of lanthanum(III) and lutetium(III) complexes within AM1 (J. Phys.
      Chem. A 2006, 110, 5897) has been extended to PM3. As training sets, we used the
      same two groups, one for each lanthanide, of 15 high-crystallographic-quality (R
      factor < 0.05 A) complexes as was previously chosen to parametrize Sparkle/AM1.
      Likewise, in the validation procedure, we used the same Sparkle/AM1 validation
      sets of 60 additional La(III) and 15 additional Lu(III) complexes. The
      Sparkle/PM3 unsigned mean errors for all interatomic distances between the metal
      ions and the ligand atoms of the first sphere of coordination proved to be random
      around the means of 0.068 A for lanthanum(III) and 0.076 A for lutetium(III),
      thus being comparable to the respective Sparkle/AM1 values of 0.078 and 0.075 A.
      Furthermore, effective-core-potential ab initio calculations on smaller subsets
      of such complexes led to similar accuracies. Sparkle/PM3 and Sparkle/AM1 are
      therefore made available to the researcher who must decide which of the models to
      use based on considerations of the impact of either PM3 or AM1 on the description
      of the ligands and the consequence of such a choice on the properties of
      interest.

PMID- 17506533
TI  - Is spin-component scaled second-order Moller-Plesset perturbation theory an
      appropriate method for the study of noncovalent interactions in molecules?
AB  - Testing of the spin-component scaled second-order Moller-Plesset (SCS-MP2) method
      for the computation of noncovalent interaction energies is done with a database
      of 165 biologically relevant complexes. The effects of the spin-scaling procedure
      (i.e., MP2 vs SCS-MP2), the basis set size, and the corrections for basis set
      superposition error (BSSE) are systematically examined. When using two-point
      basis set extrapolations for the correlation energy, augmentation of the atomic
      orbital basis with computationally costly diffuse functions is found to be
      obsolete. In general, SCS-MP2 also improves results for noncovalent interactions
      statistically on MP2, and significant outliers are removed. Moreover, it is shown
      that effects of BSSE and one-particle basis set incompleteness almost cancel each
      other in the case of triple-zeta sets (SCS-MP2/TZVPP or SCS-MP2/cc-pVTZ without
      counterpoise correction), which opens a practical route to efficient computations
      for large systems. We recommend SCS-MP2 as the preferred quantum chemical wave
      function based method for the noncovalent interactions in large biologically
      relevant systems when reasonable coupled-cluster with single and double and
      perturbative triple excitations (CCSD(T)) calculations cannot be performed
      anymore. A comparison to MP2 and CCSD(T) interaction energies for n-alkane
      dimers, however, indicates (and this also holds to a lesser extent for hydrogen
      bonded systems) limitations of SCS-MP2 when treating chemically "saturated"
      interactions. The different behavior of second-order perturbation theory for
      saturated and for stacked pi-systems is discussed.

PMID- 17506534
TI  - pKa analysis for the zinc-bound water in human carbonic anhydrase II: Benchmark
      for "multiscale" QM/MM simulations and mechanistic implications.
AB  - To quantitatively explore the applicability of the generalized solvent boundary
      potential (GSBP) based QM/MM approach as a "multiscale" framework for studying
      chemical reactions in biomolecules, the structural and energetic properties of
      the Human Carbonic Anhydrase II (CAII) are analyzed and compared to those from
      periodic boundary condition (PBC) simulations and available experimental data.
      Although the atomic fluctuations from GSBP based simulations are consistently
      lower compared to those from PBC simulations or crystallographic data, the
      fluctuations and internal coordinate distributions for residues in the proximity
      of the active site as well as diffusion constants of active-site water molecules
      are fairly well described by GSBP simulations. The pKa of the zinc-bound water,
      calculated with a SCC-DFTB/MM-GSBP based thermodynamic integration approach,
      agrees well with experiments for the wild type CAII. For the E106Q mutant,
      however, a 9 pKa unit downward shift relative to the wild type is found in
      contrast with previous experiments that found little change. This dramatic
      discrepancy signals a possible change in the mechanism for the interconversion
      between CO2/HCO3- in the E106Q mutant, which may be similar to the bicarbonate
      mediated mechanism proposed for the Co2+ substituted CAII (J. Am. Chem. Soc.
      2001, 123, 5861).1 The study highlights pKa analyses as a valuable approach for
      quantitatively validating the computational model for complex biomolecules as
      well as for revealing energetic properties intimately related to the chemical
      process of interest.

PMID- 17506535
TI  - Mechanism of OH radical reactions with HCN and CH3CN: OH regeneration in the
      presence of O2.
AB  - A theoretical study on the mechanism of the OH reactions with HCN and CH(3)CN, in
      the presence of O2, is presented. Optimum geometries and frequencies have been
      computed at BHandHLYP/6-311++G(2d,2p) level of theory for all stationary points.
      Energy values have been improved by single-point calculations at the above
      geometries using CCSD(T)/6-311++G(2d,2p). The initial attack of OH to HCN was
      found to lead only to the formation of the HC(OH)N adduct, while for CH(3)CN
      similar proportions of CH(2)CN and CH(3)C(OH)N are expected. A four-step
      mechanism has been proposed to explain the OH regeneration, experimentally
      observed for OH + CH(3)CN reaction, when carried out in the presence of O2. The
      mechanism steps are as follows: (1) OH addition to the C atom in the CN group,
      (2) O2 addition to the N atom, (3) an intramolecular H migration from OH to OO,
      and (4) OH elimination. This mechanism is in line with the one independently
      proposed by Wine et al. for HCN. The results obtained here suggest that for the
      OH + HCN reaction, the OH regeneration might occur even in larger extension than
      for OH + CH(3)CN reaction. The agreement between the calculated data and the
      available experimental evidence on the studied reactions seems to validate the
      mechanism proposed here.

PMID- 17506536
TI  - Insight into global reaction mechanism of [C2, H4, O] system from ab initio
      calculations by the scaled hypersphere search method.
AB  - A detailed computational study is performed on the singlet potential energy
      surface (PES) for possible isomerization and dissociation reactions of CH(3)CHO
      at the DFT (B3LYP/6-311++G(d,p)) and CCSD(T)/cc-pVTZ//B3LYP/6-311++G(d,p) levels.
      The pathways around the equilibrium structures can be discovered by the scaled
      hypersphere search (SHS) method, which enables us to make a global analysis of
      the PES for a given chemical composition. Fourteen isomers inclusive of 11 single
      molecules and three "non-stabilized" oxygen-based ylides, 5 energetically favored
      complexes, and 79 interconversion transition states have been found on the
      singlet PES. Four lowest lying isomers with thermodynamic stability are also
      kinetically stable with respect to metastable intermediates. It was revealed that
      vinyl alcohols, which could be generated by the tautomerization of acetaldehyde,
      could undergo dissociation to form acetylene and water. In addition,
      recombination channels between some fragments, such as H(2)CO + (1)CH(2) and
      (1)CHOH + (1)CH(2), are energetically accessible via collision complex or oxygen
      based ylides. Most of available unimolecular decompositions are found to be
      responsible for favorable hydrogen abstraction processes.

PMID- 17506537
TI  - Density functional theory calculations and vibrational circular dichroism of
      aromatic foldamers.
AB  - Ab initio calculations together with vibrational circular dichroism (VCD) have
      been used for studying the conformations of a quinoline-derived oligoamide
      bearing a terminal chiral residue. Three helically folded conformers of the
      dimer, trimer, and tetramer forms of the oligomer were optimized at the density
      functional theory (DFT) level using the B3LYP functional and the 6-31G* basis
      set. For each form, the three conformers differ in their helical handedness and
      in the conformation of the chiral end group. The calculated structures of the
      tetramer and also the proportions predicted between them based on their
      calculated Gibbs free energies differences match remarkably well with
      experimental data collected on an octamer. Specifically, a R-phenethyl terminal
      group gives rise to a 91:9 ratio between left handed and right handed helices.
      The predicted VCD spectrum calculated from the Boltzmann population of the
      individual conformer reproduces very well the experimental VCD spectrum of the
      tetramer in CDCl3 solution. The DFT calculations performed for the trimer also
      allow one to assess the preferred handedness of the helix and the conformation of
      the chiral end group, but the calculated relative populations differ slightly
      from experimental data. Finally, this study shows that the dimer fragment is not
      sufficient to obtain valuable information on the conformation of this aromatic
      oligoamide foldamer.

PMID- 17506538
TI  - Synthesis and biological studies of novel 2-aminoalkylethers as potential
      antiarrhythmic agents for the conversion of atrial fibrillation.
AB  - A series of 2-aminoalkylethers prepared as potential antiarrhythmic agents is
      described. The present compounds are mixed sodium and potassium ion channel
      blockers and exhibit antiarrhythmic activity in a rat model of ischemia-induced
      arrhythmias. Structure-activity studies led to the identification of three
      compounds 5, 18, and 26, which were selected based on their particular in vivo
      electrophysiological properties, for studies in two canine atrial fibrillation
      (AF) models. The three compounds converted AF in both models, but only compound
      26 was shown to be orally bioavailable. Resolution of the racemate 26 into its
      corresponding enantiomers 40 and 41 and subsequent biological testing of these
      enantiomers led to the selection of (1S,2S)-1-(1-naphthalenethoxy)-2-(3
      ketopyrrolidinyl)cyclohexane monohydrochloride (41) as a potential atrial
      selective antiarrhythmic candidate for further development.

PMID- 17506539
TI  - Relaxation dynamics of piroxicam structures within human serum albumin protein.
AB  - We report on steady-state and ps-time-resolved emission studies of piroxicam (1)
      drug within human serum albumin (HSA) protein in cyclodextrin and in neat
      solvents. The steady-state results indicate that 1 binds to HSA protein and that
      two binding sites are involved. The fluorescence decays corresponding to site I
      in subdomain IIA and to site II in subdomain IIIA have time constants of
      approximately 60 ps and approximately 360 ps, respectively. The results suggest
      that the anion forms bind to site I, whereas the zwitterionic ones bind to site
      II. The energy-transfer process from excited tryptophan to 1 can occur with
      moderate efficiency (50%). The rotational time of 1 encapsulated by HSA indicates
      diffusion within the protein. These findings can be used for a better
      understanding of piroxicam and HSA interactions.

PMID- 17506540
TI  - Comparative molecular field analysis of the binding of the stereoisomers of
      fenoterol and fenoterol derivatives to the beta2 adrenergic receptor.
AB  - Stereoisomers of fenoterol and six fenoterol derivatives have been synthesized
      and their binding affinities for the beta2 adrenergic receptor (Kibeta2-AR), the
      subtype selectivity relative to the beta1-AR (Kibeta1-AR/Kibeta2-AR) and their
      functional activities were determined. Of the 26 compounds synthesized in the
      study, submicromolar binding affinities were observed for (R,R)-fenoterol, the
      (R,R)-isomer of the p-methoxy, and (R,R)- and (R,S)-isomers of 1-naphthyl
      derivatives and all of these compounds were active at submicromolar
      concentrations in cardiomyocyte contractility tests. The Kibeta1-AR/Kibeta2-AR
      ratios were >40 for (R,R)-fenoterol and the (R,R)-p-methoxy and (R,S)-1-naphthyl
      derivatives and 14 for the (R,R)-1-napthyl derivative. The binding data was
      analyzed using comparative molecular field analysis (CoMFA), and the resulting
      model indicated that the fenoterol derivatives interacted with two separate
      binding sites and one steric restricted site on the pseudo-receptor and that the
      chirality of the second stereogenic center affected Kibeta2 and subtype
      selectivity.

PMID- 17506541
TI  - Identification and quantification of basic and acidic proteins using solution
      based two-dimensional protein fractionation and label-free or 18O-labeling mass
      spectrometry.
AB  - Reduction in sample complexity enables more thorough proteomic analysis using
      mass spectrometry (MS). A solution-based two-dimensional (2D) protein
      fractionation system, ProteomeLab PF 2D, has recently become available for sample
      fractionation and complexity reduction. PF 2D resolves proteins by isoelectric
      point (pI) and hydrophobicity in the first and second dimensions, respectively.
      It offers distinctive advantages over 2D gel electrophoresis with respects to
      automation of the fractionation processes and characterization of proteins having
      extreme pIs. Besides fractionation, PF 2D is equipped with built-in UV detectors
      intended for relative quantification of proteins in contrasting samples using its
      software tools. In this study, we utilized PF 2D for the identification of basic
      and acidic proteins in mammalian cells, which are generally under-characterized.
      In addition, mass spectrometric methods (label-free and 18O-labeling) were
      employed to complement protein quantification based on UV absorbance. Our studies
      indicate that the selection of chromatographic fractions could impact protein
      identification and that the UV-based quantification for contrasting complex
      proteomes is constrained by coelution or partial coelution of proteins. In
      contrast, the quantification post PF 2D chromatography based on label-free or 18O
      labeling mass spectrometry provides an alternative platform for basic/acidic
      protein identification and quantification. With the use of HCT116 colon carcinoma
      cells, a total of 305 basic and 183 acidic proteins was identified. Quantitative
      proteomics revealed that 17 of these proteins were differentially expressed in
      HCT116 p53-/- cells.

PMID- 17506542
TI  - Proteomics study reveals cross-talk between Rho guanidine nucleotide dissociation
      inhibitor 1 post-translational modifications in epidermal growth factor
      stimulated fibroblasts.
AB  - Following stimulation of NRK49F rat kidney fibroblast cells with epidermal growth
      factor, possible preemptive cross-talk between arginine methylation and serine
      and tyrosine phosphorylation was observed for Rho guanidine nucleotide
      dissociation inhibitor 1 (RhoGDI-1). Five dimethylation sites (Lys50, Lys52,
      Arg111, Arg152, Arg180) and two new phosphorylation sites (Tyr144, Ser148) were
      identified for RhoGDI-1. All presently known phosphorylation sites for RhoGDI-1
      lie within the 10 residues immediately prior to the 3 sites for arginine
      dimethylation, and these dimethylation/phosphorylation modules may constitute
      functional switches. Consideration of structural data and other literature for
      RhoGDI-1 suggests that methylation and phosphorylation cooperatively affect
      formation of complexes with different Rho/Rac family proteins and that
      methylation may be crucial in partitioning of RhoGDI-1 between different
      functional roles. On the basis of results presented here, it can be implied that
      unidentified arginine methyltransferases may exist and that arginine methylation
      may have a greater role in cellular signaling processes than is currently
      recognized. The combined use of SILAC labeling of arginine (SILAC = stable
      isotope labeling by amino acids in cell culture), immobilized metal affinity
      chromatography based phosphoprotein enrichment, and mass spectrometry is clearly
      a useful method for this investigation.

PMID- 17506543
TI  - Stabilization of a transition-state analogue at the active site of yeast cytosine
      deaminase: importance of proton transfers.
AB  - It is believed that the binding of pyrimidin-2-one to cytosine deaminase (CD)
      leads to the formation of 4-[R]-hydroxyl-3,4-dihydropyrimidine (DHP). Here the
      formation of transition-state analogue (TSA) at the active site of yeast cytosine
      deaminase (yCD) is investigated by quantum mechanical/molecular mechanical
      (QM/MM) molecular dynamics (MD) and free energy simulations. It is shown that DHP
      may in fact be unstable in the active site and a proton transfer from the Zn
      hydroxide group to Glu-64 may occur during the nucleophilic attack, leading to an
      alkoxide-like TSA complex instead. The free energy simulations for the
      nucleophilic attack process show that the proton transfer from the Zn hydroxide
      to Glu-64 may play an important role in stabilizing the TSA complex.

PMID- 17506544
TI  - Photochemical and photophysical properties of three carbon-bridged fullerene
      dimers: C121 (I, II, III).
AB  - The photochemical and photophysical properties of the three C121 isomers (I, II,
      III) were investigated with MADLI-TOF-MS, UV-vis spectra, fluorescence spectra,
      absorption spectra of their DMA complexes, and theoretical calculations. The
      three isomers of C121 (I, II, III) have different stabilities under laser
      irradiation, but isomer I and isomer II show good stability against the heat
      induced conversion between different isomers: No conversion between the isomers
      was found after heating the mixture of isomer I and isomer II at 353 K for 12 h
      in Ar atmosphere. The results of UV-vis absorption and fluorescence spectra
      indicate that interactions between two C60 moieties of C60=C=C60 in the ground
      and singlet states are not significant, C121 (I, II, III) behaves as an electron
      acceptor similar to C60. These indicate that the formation of the fullerene chain
      structure (e.g., C60=C=C60) does not disturb the photochemical and photophysical
      properties of the C60 monomer itself, even that the properties were enhanced by
      the formation of the polymer. This is significant for the C60 polymer in
      photochemical or photoelectronic applications in which C60=C=C60 can be an
      excellent basic unit of polymers.

PMID- 17506545
TI  - Using ionic strength to control liquid-ordered/liquid-disordered separation.
AB  - In this Letter, we will show that liquid-ordered/liquid-disordered separation can
      be controlled with ionic strength. Using this observation, a robust method was
      developed for creating visible, by fluorescence microscopy, liquid-ordered
      domains in supported lipid bilayers. The details of the method will be discussed.

PMID- 17506546
TI  - Scanning tunneling microscopy study of DNA-chromophore motif on solid surfaces.
AB  - We focus our studies on DNA-chromophore motif on surfaces using samples prepared
      by the synthetic methods described by Wang and Li in a recent publication (J. Am.
      Chem. Soc. 2003, 125, 5248-5249). Scanning tunneling microscope (STM) was used to
      investigate the DNA-chromophore hybrids adsorbed on Au(111) and highly oriented
      pyrolytic graphite (HOPG) surfaces at room temperature in air. Experiments found
      that the DNA-chromophore hybrid molecules easily formed multimolecule
      aggregations on gold surface. On HOPG surfaces, however, DNA-chromophore hybrids
      were usually adsorbed as single molecules. STM images further showed DNA
      chromophore hybrids adsorbed on Au(111) surfaces existed in the form of single
      molecule, dimer, trimer, tetramer, etc. The occurrence of molecular aggregations
      indicates that molecular interactions are comparable or stronger than molecule
      substrate interactions; such weak interactions control the geometrical sizes and
      topographical shapes of the self-assembled DNA-chromophore hybrids on surfaces.

PMID- 17506547
TI  - Effects of OH radical addition on proton transfer in the guanine-cytosine base
      pair.
AB  - Double proton transfer (PT) reactions in guanine-cytosine OH radical adducts are
      studied by the hybrid density functional B3LYP approach. Concerted and stepwise
      proton-transfer processes are explored between N1(H) on guanine (G) and N3 on
      cytosine (C), and between N4(H) on C and O6 on G. All systems except GC6OH
      display a concerted mechanism. 8OHGC has the highest dissociation energy and is
      1.2 kcal/mol more stable than the nonradical GC base pair. The origin of the
      interactions are investigated through the estimation of intrinsic acid-basic
      properties of the *OH-X monomer (X = G or C). Solvent effects play a significant
      role in reducing the dissociation energy. The reactions including *OH-C adducts
      have significantly lower PT barriers than both the nonradical GC pair and the *OH
      G adducts. All reactions are endothermic, with the GC6OH --> GC6OHPT reaction has
      the lowest reaction energy (4.6 kcal/mol). In accordance with earlier results,
      the estimated NBO charges show that the G moiety carries a slight negative charge
      (and C a corresponding positive one) in each adduct. The formation of a partial
      ion pair may be a potential factor leading to the PT reactions being
      thermodynamically unfavored.

PMID- 17506548
TI  - A structural and theoretical investigation of equatorial cis and trans uranyl
      phosphinimine and uranyl phosphine oxide complexes UO2Cl2(Cy3PNH)2 and
      UO2Cl2(Cy3PO)2.
AB  - Phosphinimine ligands (Cy3PNH) readily react with UO2Cl2(THF)3
      (THF=tetrahydrofuran) to give UO2Cl2(Cy3PNH)2, which contains strong U-N
      interactions and exists as cis and trans isomers in the solid and solution state.
      Solution NMR experiments and computational analysis both support the trans form
      as the major isomer in solution, although the cis isomer becomes more stabilized
      with an increase in the dielectric constant of the solvent. Mayer bond orders,
      energy decomposition analysis, and examination of the molecular orbitals and
      total electron densities support a more covalent bonding interaction in the U
      NHPCy3 bond compared with the analogous bond of the related U-OPCy3 compounds.

PMID- 17506549
TI  - Simple general method of generating non-oxo, non-amavadine model octacoordinated
      vanadium(IV) complexes of some tetradentate ONNO chelating ligands from various
      oxovanadium(IV/V) compounds and structural characterization of one of them.
AB  - A simple general route of obtaining very stable octacoordinated non
      oxovanadium(IV) complexes of the general formula VL2 (where H2L is a tetradentate
      ONNO donor) is presented. Six such complexes (1-6) are adequately characterized
      by elemental analysis, mass spectrometry, and various spectroscopic techniques.
      One of these compounds (1) has been structurally characterized. The molecule has
      crystallographic symmetry and has a dodecahedral structure existing in a
      tetragonal space group Pn2. The non-oxo character and VL2 stoichiometry for all
      of the complexes are established from analytical and mass spectrometric data. In
      addition, the non-oxo character is clearly indicated by the complete absence of
      the strong nuV=O band in the 925-1025 cm-1 region, which is a signature of all
      oxovanadium species. The complexes are quite stable in open air in the solid
      state and in solution, a phenomenon rarely observed in non-oxovanadium(IV) or
      bare vanadium(IV) complexes.

PMID- 17506550
TI  - fac-[Re(CO)3(H2O)3]+ nucleoside monophosphate adducts investigated in aqueous
      solution by multinuclear NMR spectroscopy.
AB  - The fac-[Re(CO)3(H2O)3]+ cation, the putative DNA-binding species accounting for
      the biological activity of related Re(I) complexes, binds reversibly to N7 of 6
      oxopurine nucleotide monophosphates (NMPs), in contrast to Pt(II) anticancer
      drugs. A relatively high amount of NMP is needed to convert all of the fac
      [Re(CO)3(H2O)3]+ to adducts. The Re/nucleotide 1:1 adduct forms more rapidly and
      builds up to a higher concentration for guanosine 5'-monophosphate (5'-GMP) and
      inosine 5'-monophosphate (5'-IMP) than for the respective 3'-monophosphates (3'
      GMP and 3'-IMP). These results are attributable to the 5'-positioning of the 5'
      NMP phosphate group that allows it to approach the metal inner sphere for more
      favorable cation electrostatic and aqua ligand H-bonding interactions, both in
      the initial productive ion pair encounter complexes and in the N7-bound 1:1
      adducts. A higher reactivity of 5'-GMP over 3'-GMP is known for cisplatin. In
      contrast, more Re/nucleotide 1:2 adduct was formed by 3'-GMP (and 3'-IMP) than by
      5'-GMP (and 5'-IMP). Because the 3'-phosphate group cannot closely approach the
      metal inner coordination sphere, the greater stability for the 3'-GMP 1:2 adduct
      reflects the more favorable G N1H-phosphate interligand GMP-GMP interactions for
      3'-GMP vs 5'-GMP (G=guanine base derivative). This type of interaction is known
      for platinum adducts. In 1:2 adducts the bound nucleotides are inequivalent,
      prompting us to perform mixed 5'-GMP/3'-GMP experiments, leading to the
      observation of major (M) and minor (m) mixed Re/5'-GMP/3'-GMP 1:1:1 adducts. The
      order of abundance at equilibrium in a typical experiment was M>bis 3'
      GMP>m>or=bis 5'-GMP. This stability order was rationalized by invoking the
      phosphate interactions described above. When methionine and 5'-GMP were allowed
      to compete for fac-[Re(CO)3(H2O)3]+, the Re/5'-GMP 1:1 adduct was the kinetic
      product and the S-bound Re/methionine adduct was the thermodynamic product, a
      result opposite to that typically found for cisplatin.

PMID- 17506551
TI  - Isolated heterometallic Cr7Ni rings grafted on Au(111) surface.
AB  - A study of the deposition of heterometallic antiferromagnetically coupled rings
      onto gold surfaces is reported. Two new {Cr7Ni} rings, [NH2nPr2][Cr7NiF8(3
      tpc)16] (1) (where 3-tpc=3-thiophenecarboxylate) and [nBuNH2CH2CH2SH]
      [Cr7NiF8(O2CtBu)16] (2) have been made and structurally characterized. They have
      been deposited from the liquid phase on Au(111) and the adsorbed molecules
      compared by means of scanning tunneling microscopy (STM) and X-ray photoemission
      spectroscopy (XPS). In both cases a two-dimensional distribution of individually
      accessible {Cr7Ni} heterometallic rings on the gold surface has been obtained,
      exploiting the direct grafting of sulfur-functionalized clusters. There is a
      competition between the chemisorption of the {Cr7Ni} clusters and a thiolic self
      assembled monolayer (SAM) formed by free ligands. In 2, the presence of a single
      sulfur ligand should force the molecule to graft with the ring axis normal to the
      surface. The cluster stability in the STM images and the S-2p energy positions
      demonstrate, for both functionalizations, the strength of the grafting with the
      gold surface.

PMID- 17506552
TI  - Rapid injection NMR in mechanistic organocopper chemistry. Preparation of the
      elusive copper(III) intermediate.

PMID- 17506553
TI  - Organocuprate conjugate addition: the square-planar "CuIII" intermediate.

PMID- 17506555
TI  - Chain-growth polymerization for the synthesis of polyfluorene via Suzuki-Miyaura
      coupling reaction from an externally added initiator unit.

PMID- 17506554
TI  - Development of a highly specific rhodamine-based fluorescence probe for
      hypochlorous acid and its application to real-time imaging of phagocytosis.
AB  - The tetramethylrhodamine (TMR) fluorophore is a useful platform for fluorescence
      probes, being applicable, for example, to biological investigations utilizing
      fluorescence microscopy, owing to its excellent photochemical properties in
      aqueous media. We have developed new TMR derivatives that show different
      dependences of their behavior upon the environment. Among them, HMTMR showed
      unique characteristics, and its putative spirocyclic structure was confirmed by X
      ray crystallography. Utilizing this discovery, we have established a strategy to
      modulate the fluorescence of TMR by regulating the spirocyclization, and we have
      obtained a new fluorescence probe that can detect hypochlorous acid specifically.
      This probe, HySOx, can work in 99.9% aqueous solution at pH 7.4 and was confirmed
      to be able to detect hypochlorous acid being generated inside phagosomes in real
      time. HySOx is tolerant to autoxidation and photobleaching under bioimaging
      conditions. Regulation of the spirocyclization of rhodamines, as we describe
      here, provides a new approach to the rational development of novel fluorescence
      probes.

PMID- 17506556
TI  - Self-organization of all-inorganic dodecatungstophosphate nanocrystallites.
AB  - The crystallinity and porosity of all-inorganic dodecatungstophosphate M3PW12O40
      (M=Cs, NH4, Ag, denoted as MPW) particles are controlled by the changes in the
      synthetic temperatures and countercations. The MPW particles can be classified
      into three groups by the crystallinity and porosity: (i) mesoporous "disordered"
      aggregates, (ii) microporous "self-organized" aggregates, and (iii) nonporous
      single crystals. The formation and growth mechanism of MPW particles is expressed
      by three steps: formation of nanocrystallites, assembly of the nanocrystallites
      to form aggregates, and the growth of aggregates by the attachment of
      nanocrystallites. The time courses of the turbidity of the synthetic solution,
      the concentration of the nanocrystallites, and the average particle sizes of MPW
      particles are well reproduced by the calculation based on the mechanism.

PMID- 17506557
TI  - Two-photon absorbing block copolymer as a nanocarrier for porphyrin: energy
      transfer and singlet oxygen generation in micellar aqueous solution.

PMID- 17506558
TI  - A solid state 13C NMR, crystallographic, and quantum chemical investigation of
      phenylalanine and tyrosine residues in dipeptides and proteins.
AB  - We report the results of a solid-state NMR and quantum chemical investigation of
      the 13C gamma NMR chemical shifts in phenylalanine and tyrosine in dipeptides and
      proteins. Accurate computation of the experimental shifts is shown to require a
      good description of local electrostatic field effects, and we find the best
      results (R2=0.94, rmsd=1.6 ppm, range = 17.1 ppm, N=14) by using a self
      consistent reaction field continuum model. There are no obvious correlations with
      phi, psi, chi 1, or chi2 torsion angles, unlike the results seen with other amino
      acids. There is, however, a linear relation between computed C gamma atomic
      charges and shifts for the 14 peptide as well as 18 protein residues
      investigated. This result is similar to the correlation reported in the 1960s
      between pi-electron density and 13C shifts for classical 4n + 2 (n=0, 1, 2) pi
      electron aromatic species, such as cyclopentadienide and the tropylium cation,
      and in fact, we found that the shielding/atomic charge correlation seen in the
      peptides and proteins is virtually identical to that seen with a broad range of
      aromatic carbocations/carbanions. These results suggest the dominance of an
      electrostatic field polarization model in which increasing pi electron density
      results in an increase in C gamma atomic charge and increased shielding (of sigma
      11 and sigma 22, perpendicular to the pi orbital) in Phe and Tyr, as well as in
      the other aromatic species. These results are of general interest since they
      demonstrate the importance of electrostatic field effects on Phe and Tyr C gamma
      chemical shifts in peptides and proteins and imply that inclusion of these
      effects will be necessary in order to interpret the shifts of other aromatic
      species, such as drug molecules, bound to proteins.

PMID- 17506559
TI  - SERS at structured palladium and platinum surfaces.
AB  - Palladium and platinum are important catalytic metals, and it would be highly
      advantageous to be able to use surface enhanced Raman spectroscopy (SERS) to
      study reactive species and intermediates on their surfaces. In this paper we
      describe the use of templated electrodeposition through colloidal templates to
      produce thin (<1 microm) films of palladium and platinum containing close packed
      hexagonal arrays of uniform sphere segment voids. We show that, even though these
      films are not rough, when the appropriate film thickness and sphere diameter are
      employed these surfaces give stable, reproducible surface enhancements for Raman
      scattering from molecules adsorbed at the metal surface. We report SERS spectra
      for benzenethiol adsorbed on the structured palladium and platinum surfaces of
      different thicknesses and void diameters and show that, for 633 nm radiation,
      enhancements of 1800 and 550 can be obtained for palladium and platinum,
      respectively.

PMID- 17506561
TI  - A facile method for permanent and functional surface modification of
      poly(dimethylsiloxane).

PMID- 17506560
TI  - VTVH-MCD and DFT studies of thiolate bonding to [FeNO]7/[FeO2]8 complexes of
      isopenicillin N synthase: substrate determination of oxidase versus oxygenase
      activity in nonheme Fe enzymes.
AB  - Isopenicillin N synthase (IPNS) is a unique mononuclear nonheme Fe enzyme that
      catalyzes the four-electron oxidative double ring closure of its substrate ACV. A
      combination of spectroscopic techniques including EPR, absorbance, circular
      dichroism (CD), magnetic CD, and variable-temperature, variable-field MCD (VTVH
      MCD) were used to evaluate the geometric and electronic structure of the [FeNO]7
      complex of IPNS coordinated with the ACV thiolate ligand. Density Function Theory
      (DFT) calculations correlated to the spectroscopic data were used to generate an
      experimentally calibrated bonding description of the Fe-IPNS-ACV-NO complex. New
      spectroscopic features introduced by the binding of the ACV thiolate at 13 100
      and 19 800 cm-1 are assigned as the NO pi*(ip) --> Fe dx2-y2 and S pi--> Fe dx2
      y2 charge transfer (CT) transitions, respectively. Configuration interaction
      mixes S CT character into the NO pi*(ip) --> Fe dx2-y2 CT transition, which is
      observed experimentally from the VTVH-MCD data from this transition. Calculations
      on the hypothetical {FeO2}8 complex of Fe-IPNS-ACV reveal that the configuration
      interaction present in the [FeNO]7 complex results in an unoccupied frontier
      molecular orbital (FMO) with correct orientation and distal O character for H
      atom abstraction from the ACV substrate. The energetics of NO/O2 binding to Fe
      IPNS-ACV were evaluated and demonstrate that charge donation from the ACV
      thiolate ligand renders the formation of the FeIII-superoxide complex
      energetically favorable, driving the reaction at the Fe center. This single
      center reaction allows IPNS to avoid the O2 bridged binding generally invoked in
      other nonheme Fe enzymes that leads to oxygen insertion (i.e., oxygenase
      function) and determines the oxidase activity of IPNS.

PMID- 17506562
TI  - Effective, selective hydroalkoxylation/cyclization of alkynyl and allenyl
      alcohols mediated by lanthanide catalysts.

PMID- 17506563
TI  - Thiolate-induced structural reconstruction of gold clusters probed by 197Au
      Mossbauer spectroscopy.

PMID- 17506564
TI  - Triplet (S=1) ground state aminyl diradical.

PMID- 17506565
TI  - Ultralong nanobelts self-assembled from an asymmetric perylene tetracarboxylic
      diimide.

PMID- 17506566
TI  - [1 + 2] cycloadditions of sulfur monoxide (SO) to alkenes and alkynes and [1 + 4]
      cycloadditions to dienes (polyenes). Generation and Reactions of Singlet SO?

PMID- 17506567
TI  - Tailored glycoproteomics and glycan site mapping using saccharide-selective
      bioorthogonal probes.

PMID- 17506569
TI  - Formation of hydroxyphenyl-pyranoanthocyanins in Grenache wines: precursor levels
      and evolution during aging.
AB  - Grenache red wines were produced following three different winemaking techniques,
      that is, small-scale standard experimental wines and industrial-scale wines by
      both double-mash fermentation and fermentation in Ganimede vats. Wines were
      analyzed for their color properties, as well as the anthocyanin, flavonol,
      hydroxycinnamic acid, and pyranoanthocyanin profiles following alcoholic and
      malolactic fermentation. The evolution of pyranoanthocyanins and their
      corresponding precursors in the experimental wines was monitored at 6 and 10
      months of aging. Wines produced by double-mash fermentation exhibited superior
      color properties compared to Ganimede wines and the experimental red wines, due
      to better extraction of flavonols and anthocyanins as well as a lower degree of
      polymerization. Pyranoanthocyanin formation varied within the different classes
      of pigments. Vitisins A and B were formed only during alcoholic fermentation.
      Pinotin A (i.e., the reaction product from malvidin 3-glucoside and caffeic acid)
      formation took place only during the aging process, whereas formation of
      hydroxyphenyl-pyranoanthocyanins derived from p-coumaric and ferulic acid
      followed two different pathways, that is, an enzymatically assisted production
      during fermentation and a pure chemical formation during aging.

PMID- 17506570
TI  - High-level expression of milk-derived antihypertensive peptide in Escherichia
      coli and its bioactivity.
AB  - An optimal antihypertensive peptide (AHP), KVLPVP, was linked to form a six-copy
      of tandem dotetracontapeptide with the specific cleavage site (Arg-X) of
      clostripain. The gene of the dotetracontapeptide was synthesized and expressed in
      Escherichia coli BL21. After a 5 h induction with 1.2 mM isopropyl-beta-D
      thiogalactopyranoside the recombinant AHP fused with glutathione-S-transferase
      tag reached the maximal production, 24.6% of total intracellular protein.
      Following digestion with clostripain and carboxypeptidase B, the product was
      separated with ultrafiltration and reversed-phase HPLC, and 170 mg of pure
      recombinant AHP was obtained from 1 L of E. coli culture. The IC50 of the
      recombinant AHP was 4.6 microM. The systolic blood pressure of spontaneously
      hypertensive rats could be decreased dramatically by the recombinant AHP in a
      dose-dependent manner after delivering 0.3 mg of AHP/kg of body weight (BW) or
      0.6 mg of AHP/kg of BW orally. The strong antihypertensive effect was reached 4
      24 h after oral administration of 0.3 mg of AHP/kg of BW, and the peak point was
      at the fourth hour (-21.4 +/- 7.2 mm of Hg). This study overcame traditional
      enzymatic digestion problems in preparing AHP and established a novel approach
      for industrial production of AHP.

PMID- 17506571
TI  - Hydrophilic chromatographic determination of carnosine, anserine, balenine,
      creatine, and creatinine.
AB  - A new HPLC procedure based on hydrophilic interaction chromatography (HILIC) has
      been developed for the simultaneous determination of carnosine, anserine,
      balenine, creatine, and creatinine in meat. This is the first time that HILIC has
      been directly applied to the study of meat components, having the advantage of
      not requiring complex cleanup and/or sample derivatization procedures. The
      chromatographic separation has been developed using a silica column (4.6 x 150
      mm, 3 microm), and the proposed methodology is simple, reliable, and fast (<13
      min per sample). The method has been validated in terms of linearity,
      repeatability, reproducibility, and recovery and represents an interesting
      alternative to methods currently in use for determining the mentioned compounds
      and other polar substances. The detection limits are 5.64, 8.23, 3.66, 3.99, and
      0.06 microg/mL for carnosine, anserine, balenine, creatine, and creatinine,
      respectively.

PMID- 17506572
TI  - Photochemically-activated probes of protein-protein interactions.
AB  - The activity of light-activatable ("caged") compounds can be temporally and
      spatially controlled, thereby providing a means to interrogate intracellular
      biochemical pathways as a function of time and space. Nearly all caged peptides
      contain photocleavable groups positioned on the side chains of key residues. We
      describe an alternative active site targeted strategy that disrupts the
      interaction between the protein target (SH2 domain, kinase, and proteinase) and a
      critical amide NH moiety of the peptide probe.

PMID- 17506573
TI  - A liquid-phase approach to functionalized Janus dendrimers: novel soluble
      supports for organic synthesis.
AB  - A new kind of functionalized Janus dendrimer has been synthesized via a liquid
      phase approach, which could easily be purified using a simple precipitation
      method without the need for chromatographic separation. Their use for liquid
      phase organic synthesis has been achieved in the Pd-catalyzed Suzuki coupling
      reactions, giving biaryl products in excellent yields after cleavage.

PMID- 17506574
TI  - An easy synthetic approach to pyridoporphyrins by domino reactions.
AB  - Beta-amino-meso-tetraarylporphyrins react with cyclic enol ethers to yield
      pyrido[2,3-b]porphyrins bearing two vicinal hydroxyalkyl groups. These reactions
      are catalyzed by lanthanum triflate and occur under mild conditions.
      Esterification of the hydroxyalkyl groups with succinic anhydride and dodecanoyl
      chloride afforded the corresponding esters in almost quantitative yields. The
      crystal structure of the most hydrophobic derivative 7 was determined, and it
      shows that these porphyrinic macrocycles form one-dimensional supramolecular
      tapes in the solid state.

PMID- 17506575
TI  - Stereoselective olefin isomerization leading to asymmetric quaternary carbon
      construction.
AB  - Chemo- and stereoselective Ir(I)-catalyzed isomerization of 1,1-disubstituted and
      trisubstituted allylic ethers and in situ [3,3] sigmatropic rearrangement of the
      resulting allyl vinyl ethers provide for the highly stereoselective construction
      of quaternary carbon stereocenters. The olefin isomerization-Claisen
      rearrangement (ICR) sequence allows adjacent quaternary-tertiary stereocenter
      relationships to be established with excellent diastereoselection. Several
      complementary strategies for enantioselective quaternary carbon synthesis derive
      directly from the ICR reaction design.

PMID- 17506576
TI  - Introduction of a triazole amino acid into a peptoid oligomer induces turn
      formation in aqueous solution.
AB  - Peptoids are a non-natural class of oligomers that are composed of repeating N
      substituted glycine units and are capable of folding into helices that mimic
      peptide structure and function. In this letter, we report the concise synthesis
      of a 1,5-substituted triazole amino acid (Tzl) and its subsequent incorporation
      into a short peptoid. The Tzl amino acid was shown to induce turn formation in
      aqueous solution, thus expanding the structural repertoire available to peptoid
      chemists.

PMID- 17506577
TI  - Intramolecular electron transfer initiated cation and radical formation through
      carbon-carbon bond activation.
AB  - Radical cations can be formed in a spatially and temporally controlled manner by
      appending a sacrificial photooxidant to an easily oxidized substrate, leading to
      intramolecular electron transfer upon irradiation. The anthraquinone carboxyl
      group is an effective photooxidant that can promote single electron oxidation
      from an appended arene. The resulting intermediates undergo a cleavage reaction
      through carbon-carbon bond activation to provide either cations or radicals that
      react to form a range of products.

PMID- 17506578
TI  - Solvent-free thermal and microwave-assisted [3 + 2] cycloadditions between
      stabilized azomethine ylides and nitrostyrenes. An experimental and theoretical
      study.
AB  - The stereochemical outcomes observed in the thermal and microwave-assisted [3 +
      2] cycloaddition between stabilized azomethine ylides and nitrostyrenes have been
      analyzed using experimental and computational approaches. It has been observed
      that, in the absence of solvent, three stereoisomers are formed, both under
      classical heating conditions and under microwave irradiation. This result
      contrasts with that observed in solution under classical thermal conditions. The
      4-nitropyrrolidines obtained in this way can be aromatized under further
      microwave irradiation to yield mixtures of pyrroles and 4-nitropyrroles. It is
      found that ground state cycloadditions between imines and nitrostyrenes take
      place by three-step mechanisms. The first step involves enolization of the
      starting imine, and this is followed by a pseudopericyclic 10-electron [1.4]
      hydrogen shift. Finally, the cycloaddition takes place by a relatively
      asynchronous aromatic six-electron supra-supra thermal mechanism.

PMID- 17506579
TI  - New chiral binaphthalene-derived iminium salt organocatalysts for asymmetric
      epoxidation of alkenes.
AB  - A series of binaphthalene-fused azepinium salts has been generated and used as
      organocatalysts in the asymmetric epoxidation of unfunctionalized alkenes, giving
      rise to ees of up to 84%.

PMID- 17506580
TI  - Deprotonation and regioselective addition of 2H-pyrazolo[3,4-c]quinolines to
      electrophiles.
AB  - The deprotonation and regioselective reaction of 2H-pyrazolo[3,4-c]quinolines
      with a variety of electrophiles is described. Electrophiles include benzaldehyde,
      DMF, carbon dioxide, and iodine. This method provides a direct route to a class
      of pharmacologically interesting compounds.

PMID- 17506581
TI  - Toward a mechanistic understanding of the photochromism of
      dimethyldihydropyrenes.
AB  - A mechanism accounting for the photochromic properties of dimethyldihydropyrene
      (DHP)/metacyclophanediene (CPD) is proposed based on high-level CASSCF/CASPT2 ab
      initio calculations. The very low ring-opening quantum yield observed upon
      irradiation of DHP is explained by the quenching of the photoisomerization
      channel by internal conversion of the initially excited zwitterionic state to the
      lowest excited state minimum, where the system can fluoresce or decay back to the
      ground state via another internal conversion. On the other hand, irradiation of
      CPD leads to the formation of a biradical excited state minimum along the ring
      closure reaction path. Internal conversion back to the ground state can then
      occur at a well-characterized conical intersection, leading to the DHP
      photoproduct. Thus, our results point unambiguously toward a stepwise mechanism
      involving the formation of a biradical intermediate on a singlet excited state.
      The fact that this intermediate does not correspond to the lowest excited state
      minimum is mainly responsible for the inefficiency of this system.

PMID- 17506582
TI  - Structural revision of terpenoids with a (3Z)-2-methyl-3-penten-2-ol moiety by
      the synthesis of (23E)- and (23Z)-cycloart-23-ene-3beta,25-diols.
AB  - Synthesis of (23E)-cycloart-23-ene-3beta,25-diol (1) and its 23Z-isomer 2 was
      achieved by using cycloartenol as a starting material, thus revising the proposed
      structure of natural 2 to 1 unequivocally. These synthetic studies revealed that
      the structural revision (Z-form --> E-form) should also be applied to terpenoids
      such as (23Z)-3beta-acetoxyeupha-7,23-diene-25-ol, (23Z)-tirucalla-7,23-diene
      3beta,25-diol, quadrangularol A, quadrangularic acid K, and daurichromene C.

PMID- 17506583
TI  - Easy access to new heterocyclic systems: 1,4-oxazine and substituted 1,4
      oxazines.
AB  - In the course of our investigations on the synthesis of new nitrogen heterocyclic
      derivatives, we were interested in the synthesis and study of new 1,4-oxazine
      rings. To this aim, the desired bisvinylphosphate was prepared from N-Boc
      morpholine-3,5-dione and was then engaged in palladium-catalyzed reactions
      (reduction, Suzuki, and Stille cross-coupling reactions). The 1,4-oxazine and its
      corresponding 3,5-disubstituted derivatives were obtained in fair to good yields
      and were then functionalized under anionic conditions.

PMID- 17506584
TI  - Highly diastereoselective synthesis of beta-carboxy-gamma-lactams and their ethyl
      esters via Sc(OTf)(3)-catalyzed imino Mukaiyama-aldol type reaction of 2,5
      bis(trimethylsilyloxy)furan with imines.
AB  - Functionalized gamma-lactams are found to be crucial intermediates in the
      synthesis of biologically important natural products. We herein described a
      highly diastereoselective synthesis of beta-carboxy-gamma-lactams and their ethyl
      ester derivatives, in high yields with high diastereomeric ratio, via the
      Mukaiyama-aldol type reaction of 2,5-bis(trimethysilyloxy)furan with imines,
      employing Sc(OTf)(3) as a catalyst.

PMID- 17506585
TI  - Lemnalosides A-D, decalin-type bicyclic diterpene glycosides from the marine soft
      coral Lemnalia sp.
AB  - Four new decalin-type bicyclic diterpenoids, lemnalosides A-D (1-4), along with
      one known decalin-type bicyclic diterpenoid, lemnabourside (5), were isolated
      from an extract of the marine soft coral Lemnalia sp. The structures of the new
      compounds were elucidated on the basis of spectroscopic analysis including 1H-1H
      COSY, HMQC, HMBC, NOESY, HRESIMS, UV, IR, and chemical means. Compound 1 showed
      moderate activity in the hyphae formation inhibition (HFI) assay against
      Streptomyces 85E at a concentration of 20 microg/disk, while compound 2 displayed
      inhibitory activity in the HFI assay at a concentration of 2.5 microg/disk.

PMID- 17506586
TI  - Effect of concentration and temperature on surface tension of sodium hyaluronate
      saline solutions.
AB  - The effect of concentration and temperature on the surface tension of sodium
      hyaluronate (NaHA) saline solutions was investigated using the technique of the
      shape of pendant drops. The decay rate of the surface tension with the increase
      of NaHA concentration was well-described by the empirical Hua-Rosen equation.
      Adsorption at the air-liquid interface was estimated using the Gibbs equation.
      The temperature dependence of a dilute solution and a semidilute entangled
      solution was numerically fitted with a second-order polynomial equation. The
      surface behavior of the NaHA saline solutions was interpreted in terms of their
      known viscoelastic properties.

PMID- 17506587
TI  - Protein adhesion on silicon-supported hyperbranched poly(ethylene glycol) and
      poly(allylamine) thin films.
AB  - Hyperbranching poly(allylamine) (PAAm) and poly(ethylene glycol) (PEG) on silicon
      and its effect on protein adhesion was investigated. Hyperbranching involves
      sequential grafting of polymers on a surface with one of the components having
      multiple reactive sites. In this research, PAAm provided multiple amines for
      grafting PEG diacrylate. Current methodologies for generating PEG surfaces
      include PEG-silane monolayers or polymerized PEG networks. Hyperbranching
      combines the nanoscale thickness of monolayers with the surface coverage afforded
      by polymerization. A multistep approach was used to generate the silicon
      supported hyperbranched polymers. The silicon wafer surface was initially
      modified with a vinyl silane followed by oxidation of the terminal vinyl group to
      present an acid function. Carbodiimide activation of the surface carboxyl group
      allowed for coupling to PAAm amines to form the first polymer layer. The polymers
      were hyperbranched by grafting alternating PEG and PAAm layers to the surface
      using Michael addition chemistry. The alternating polymers were grafted up to six
      total layers. The substrates remained hydrophilic after each modification. Static
      contact angles for PAAm (32-44 degrees) and PEG (33-37 degrees) were
      characteristic of the corresponding individual polymer (30-50 degrees for
      allylamine, 34-42 degrees for PEG). Roughness values varied from approximately 1
      to 8 nm, but had no apparent affect on protein adhesion. Modifications
      terminating with a PEG layer reduced bovine serum albumin adhesion to the surface
      by approximately 80% as determined by ELISA and radiolabel binding studies. The
      hyperbranched PAAm and PEG surfaces described in this paper are nanometer-scale,
      multilayer films capable of reducing protein adhesion.

PMID- 17506588
TI  - Delapril plus indapamide: a review of the combination in the treatment of
      hypertension.
AB  - Although many data indicate that the management of hypertension has improved over
      the last two decades, there is still a large proportion of hypertensive
      individuals who do not receive adequate management of their blood pressure (BP).
      Combination therapy with two or more antihypertensive agents from different drug
      classes is increasingly being recognised as the most effective means of achieving
      target BP values by pharmacological means, particularly in the large number of
      patients in whom monotherapy proves to be ineffective. Use of an angiotensin
      converting enzyme (ACE) inhibitor combined with a diuretic is a well established
      antihypertensive combination that is very effective because of the different, yet
      synergistic, mechanisms of actions of agents from these two drug classes.
      Delapril is a potent antihypertensive ACE inhibitor, and indapamide is a thiazide
      like diuretic with additional antihypertensive properties. The combination of
      delapril and indapamide provides renoprotective effects, and indapamide is also
      cardioprotective. Use of these two drugs together is therefore a rational
      selection for combination therapy, and one that has consistently demonstrated
      lowering of BP to target values with a level of efficacy that is at least as good
      as other combinations of ACE inhibitors and diuretics. This combination has also
      been found to provide favourable effects on haemodynamic parameters, including
      left ventricular mass index and ejection fraction. Furthermore, combining an ACE
      inhibitor and a thiazide-type diuretic has been associated with a decreased risk
      of stroke and is recommended for patients with cerebrovascular disease, a setting
      in which the combination of delapril and indapamide has therapeutic potential.
      Because of the additive mechanisms of delapril and indapamide, the dose required
      for an effective antihypertensive effect is relatively low, and the combination
      is well tolerated at such doses. In particular, metabolic effects normally
      associated with diuretics are rare at the therapeutic dose of indapamide used in
      combination with delapril, making the combination suitable for patients with
      metabolic disorders in whom diuretic therapy would otherwise not be recommended.
      Delapril 30 mg and indapamide 2.5mg have been combined in a fixed combination,
      offering the convenience of a one-tablet-per-day antihypertensive drug regimen
      for most patients, which, along with good tolerability, helps to address the
      issue of noncompliance.

PMID- 17506589
TI  - Economic burden of haematological adverse effects in cancer patients: a
      systematic review.
AB  - OBJECTIVE: Patients receiving cancer treatments commonly experience
      haematological adverse effects (AEs) related to chemotherapy or molecularly
      targeted therapies, which may be associated with high healthcare costs. The
      objective of this review was to summarise the published literature on the
      economic burden of neutropenia, thrombocytopenia and anaemia as AEs of cancer
      treatment. METHODS: A systematic search of the medical literature published
      between 1990 and 2006 was conducted using PubMed/MEDLINE, EMBASE, BIOSIS, related
      article links and supplemental searches. References selected for inclusion were
      prospective or retrospective studies specifically designed to examine the burden
      of illness, direct medical costs, indirect costs and/or cost drivers associated
      with neutropenia, thrombocytopenia and anaemia in adult cancer patients. All
      costs are reported as originally published and adjusted to 2006 US dollars.
      RESULTS: In the US, the cost of neutropenia ranged from $US 1893 (2006 value $US
      2632) per outpatient episode to $US 38,583 ($US 49,917) per febrile neutropenia
      hospitalisation. For countries outside the US, the cost of neutropenia appeared
      to be lower. The cost of thrombocytopenia ranged from $US 1035 ($US 1395) to $US
      5328 ($US 7635) per cycle or episode in the US. Costs attributable to anaemia
      ranged from $US 18,418 ($US 22,775) to $US 69,478 ($US 93,454) per year in the
      US. The costs of AEs for patients with haematological malignancies appeared to be
      up to 2-3 times higher than those for patients with solid tumours. Economic
      studies of the cost of haematological AEs specific to new molecularly targeted
      treatments for haematological malignancy have not been published. CONCLUSIONS:
      Chemotherapy-related haematological AEs result in a substantial economic burden
      on patients, payers, caregivers and society in general. Because of their burden,
      the frequency and severity of these toxicities should be one of the key factors
      in the selection of optimal treatments for patients with cancer, especially those
      with haematological malignancies. Future research is needed to assess the
      economic burden of AEs associated with new molecularly targeted treatments for
      haematological malignancies.

PMID- 17506590
TI  - Post-marketing surveillance of acarbose treatment in patients with type 2
      diabetes mellitus and subjects with impaired glucose tolerance in China.
AB  - OBJECTIVE: This open, prospective, non-interventional, non-randomised, multi
      centre postmarketing surveillance study was conducted over a mean period of 13.9
      weeks to assess the efficacy, safety and acceptance of acarbose in Chinese
      patients with type 2 diabetes mellitus and subjects with impaired glucose
      tolerance (IGT) in routine clinical practice. Subjects with IGT were included in
      analyses because acarbose has been approved for treatment of this condition since
      2002. PATIENTS AND METHODS: A total of 2550 study participants were enrolled by
      133 physicians throughout China. Efficacy parameters were the changes from
      initial visit to the end of study in glycosylated haemoglobin (HbA(1c)), fasting
      blood glucose (FBG), postprandial BG and bodyweight. RESULTS: The majority of
      study participants (74.7%) were newly diagnosed. Most (77.0%) were administered
      acarbose 50mg three times daily (the recommended standard dose in China)
      throughout the study and more than half (51.7%) received concomitant
      antihyperglycaemic treatment. Acarbose treatment reduced HbA(1c) by 1.4% to 6.7%,
      FBG by 38.5 mg/dL to 116.4 mg/dL, 2-hour postprandial BG by 92.2 mg/dL to 149.0
      mg/dL and bodyweight by 0.4 kg to 67.5 kg. Subgroup analyses for type 2 diabetes
      and IGT populations were also conducted. In diabetic patients, HbA(1c) was
      reduced by 1.4%, FBG by 42.1 mg/dL and 2-hour postprandial BG by 98.9 mg/dL.
      Marked reductions were also achieved in the IGT population (0.9% for HbA(1c),
      11.8 mg/dL for FBG and 42.9 mg/dL for 2-hour postprandial BG) despite lower
      baseline glucose levels in this group than in patients with type 2 diabetes.
      Bodyweight slightly increased in the IGT population. Only 12 acarbose-related
      adverse events, none of which was serious, were reported. The attending
      physicians assessed treatment efficacy as 'good' or 'very good' for 92.4%,
      tolerability as 'good' or 'very good' for 91.1%, and patient acceptance as 'good'
      or 'very good' for 89.8% of all study participants. CONCLUSION: Acarbose was
      efficacious, safe and well accepted by Chinese patients with type 2 diabetes and
      subjects with IGT under day-to-day treatment conditions, both as monotherapy and
      in combination with other antihyperglycaemic medication.

PMID- 17506591
TI  - A multicentre, 12-week study of imidapril and candesartan cilexetil in patients
      with mild to moderate hypertension using ambulatory blood pressure monitoring.
AB  - BACKGROUND: Twenty-four-hour ambulatory blood pressure monitoring (ABPM) provides
      the most accurate efficacy assessment of an antihypertensive agent throughout a
      24-hour dosing interval. The objective of this prospective, randomised, double
      blind, parallel-group, multicentre study was to compare the antihypertensive
      efficacy of imidapril versus candesartan cilexetil using ABPM. METHODS: After
      screening and a single-blind, placebo run-in phase, ambulatory adult patients
      with mild to moderate hypertension (defined as a mean office sitting diastolic BP
      [DBP] and systolic BP [SBP], respectively, of 90-109 mm Hg and 140-179 mm Hg, and
      a mean ABPM DBP and SBP, respectively, of >or=80 mm Hg and >or=125 mm Hg) were
      randomised to once-daily treatment with imidapril or candesartan cilexetil for 12
      weeks. ABPM was performed at baseline and at the end of the 12-week treatment
      period in 112 patients (imidapril group, n=55; candesartan cilexetil group,
      n=57). To achieve the target BP of <or=140/90 mm Hg, imidapril was titrated from
      5 mg/day to 20 mg/day and candesartan cilexetil was titrated from 4 mg/day to 16
      mg/day. RESULTS: Significant (p<0.001) and similar decreases from baseline in
      clinic mean DBP and SBP, in mean 24-hour ABPM, DBP and SBP awake and asleep, and
      in mean BP (MBP) were observed in both treatment groups. In addition, significant
      and similar reductions in DBP and SBP were observed during the early morning
      acceleration period in both treatments. The reduction in BP load was higher with
      imidapril than with candesartan cilexetil: 44.6% versus 34.5% reduction in DBP
      load and 38.0% versus 32.9% reduction in SBP load, respectively. With respect to
      the average deviation index expressing a load index, the reduction with imidapril
      was 41.0% versus 33.6% with candesartan cilexetil. The percentage of DBP dipper
      patients remained identical before and after treatment in both groups. With
      regard to SBP, the percentage of dippers increased from 38.2% to 45.5% in the
      imidapril group and decreased from 54.4% to 42.1% in the candesartan cilexetil
      group. The incidence of adverse events was similar between the treatment groups
      and no cases of dry cough were reported. CONCLUSION: Imidapril in once-daily
      doses of up to 20mg was shown to be at least as effective as candesartan
      cilexetil given in once-daily doses of up to 16 mg in reducing BP throughout the
      entire 24-hour dosing interval. Both drugs were well tolerated.

PMID- 17506592
TI  - Clodronic acid in the treatment of postmenopausal osteoporosis.
AB  - BACKGROUND: Clodronic acid, a first-generation bisphosphonate, has been
      successfully used in the treatment of high bone turnover states, Paget's disease
      and osteolytic bone metastases. However, controversies remain over its optimal
      dosage and method of administration in the treatment of postmenopausal
      osteoporosis. In this study we aimed to evaluate the effect of clodronic acid
      treatment for 3 years on bone mineral density (BMD) in women with postmenopausal
      osteoporosis. METHODS: This was a prospective, open-label, randomised, controlled
      study that was conducted in an outpatient clinic at the Bone Metabolism Unit of a
      tertiary referral centre university hospital. Thirty postmenopausal women (age
      range 48-73 years) with osteoporosis and a control group of 49 osteoporotic women
      (age range 47-74 years) received randomised therapy. The clodronic acid group of
      participants received oral doses of clodronic acid 800 mg plus elemental calcium
      500 mg and 400 IU of vitamin D daily, while the control group was treated with
      calcium and vitamin D only. BMD was measured by dual energy x-ray absorptiometry
      at yearly intervals. Biochemical markers of bone turnover were also measured.
      RESULTS: In this clinical study of postmenopausal women with osteoporosis, 36
      months of clodronic acid treatment significantly increased average femoral neck
      BMD by 3.2 +/- 2.9%, trochanter BMD by 2.2 +/- 2.9% and lumbar spine BMD by 3.1
      +/- 3%. In the control group, femoral neck, trochanter and lumbar spine BMD
      decreased by -6 +/- 2.7%, -7.3 +/- 2.5% and -5.4 +/- 2%, respectively (p<0.01,
      p<0.05 and p<0.05 for clodronic acid vs control, respectively). There was a
      significant decrease in urinary hydroxyproline (-38.3%) over 3 years in the
      clodronic acid group compared with baseline (p<0.05), while no significant change
      occurred in the control group. Clodronic acid was well tolerated and compliance
      was good. There were no clinically meaningful differences in the incidence of
      individual adverse events between the groups. CONCLUSION: These results indicate
      that daily oral administration of clodronic acid 800 mg provides benefits to
      skeletal bone density in osteoporotic postmenopausal women. Calcium and vitamin D
      supplementation alone did not prevent further bone loss.

PMID- 17506593
TI  - Effects of doxazosin and amlodipine on mean platelet volume and serum serotonin
      level in patients with metabolic syndrome: a randomised, controlled study.
AB  - BACKGROUND AND OBJECTIVE: In addition to reducing blood pressure,
      antihypertensive drugs should modify other atherosclerotic risk factors. One such
      risk factor is the prothrombotic state, which is characterised mainly by
      increased fibrinogen and plasminogen activator inhibitor-1 levels and
      abnormalities in platelet function. Platelet activity and aggregation potential
      can be estimated by measuring mean platelet volume (MPV). Serotonin plays a role
      in vasospasm and increased platelet aggregation capacity, and has been shown to
      increase MPV in vitro. However, serotonin levels and MPV have not been studied in
      the metabolic syndrome. We evaluated mean platelet volume (MPV) in patients with
      the metabolic syndrome, and compared the effects of doxazosin and amlodipine on
      MPV and serum serotonin level in patients with this condition. METHODS: Thirty
      eight patients who met the Adult Treatment Panel III criteria for the metabolic
      syndrome and 20 healthy controls were included in the study. Patients were
      randomised into two groups to receive doxazosin 4 mg/day (n=20) or amlodipine 10
      mg/day (n=18). Patients' MPV, serum serotonin, insulin, insulin sensitivity,
      fasting blood glucose and lipid profiles were measured at baseline and after 8
      weeks. RESULTS: Patients with the metabolic syndrome had a significantly higher
      MPV compared with the control group. MPV was significantly decreased in the
      doxazosin-treated group (from 6.9 +/- 1.0 fL at baseline to 6.1 +/- 1.1 fL after
      treatment; p=0.02) but not in the amlodipine-treated group (6.8 +/- 0.9 fL at
      baseline vs 6.9 +/- 1.0 fL after treatment; p=0.9). Fasting blood glucose and
      total cholesterol were also significantly decreased compared with baseline in the
      doxazosin group. In the amlodipine group, there was a significant increase in
      serum serotonin levels and a decrease in serum insulin and improved insulin
      sensitivity. CONCLUSION: In patients with the metabolic syndrome, doxazosin
      treatment not only decreases platelet activity, as measured by a change in MPV,
      but also improves metabolic abnormalities. Amlodipine also has beneficial effects
      in patients with the metabolic syndrome but has no effect on MPV.

PMID- 17506594
TI  - FISH and chips: chromosomal analysis on microfluidic platforms.
AB  - Interphase fluorescence in situ hybridisation (FISH) is a sensitive diagnostic
      tool used for the detection of alterations in the genome on cell-by-cell basis.
      However, the cost-per-test and the technical complexity of current FISH protocols
      have slowed its widespread utilisation in clinical settings. For many cancers,
      the lack of a cost-effective and informative diagnostic method has compromised
      the quality of life for patients. We present the first demonstration of a
      microchip-based FISH protocol, coupled with a novel method to immobilise
      peripheral blood mononuclear cells inside microfluidic channels. These first on
      chip implementations of FISH allow several chromosomal abnormalities associated
      with multiple myeloma to be detected with a ten-fold higher throughput and 1/10
      th the reagent consumption of the traditional slide-based method. Moreover, the
      chip test is performed within hours whereas the conventional protocol required
      days. In addition, two on-chip methods to enhance the hybridisation aspects of
      FISH have been examined: mechanical and electrokinetic pumping. Similar agitation
      methods have led to significant improvements in hybridisation efficiency with DNA
      microarray work, but with this cell-based method the benefits were moderate. On
      chip FISH technology holds promise for sophisticated and cost-effective screening
      of cancer patients at every clinic visit.

PMID- 17506595
TI  - AC electrothermal manipulation of conductive fluids and particles for lab-chip
      applications.
AB  - AC electrokinetics has shown great potential for microfluidic functions such as
      pumping, mixing and concentrating particles. So far, electrokinetics are
      typically applied on fluids that are not too conductive (<0.02 S/m), which
      excludes most biofluidic applications. To solve this problem, this paper seeks to
      apply AC electrothermal (ACET) effect to manipulate conductive fluids and
      particles within. ACET generates temperature gradients in the fluids, and
      consequently induces space charges that move in electric fields and produce
      microflows. This paper reports two new ACET devices, a parallel plate particle
      trap and an asymmetric electrode micropump. Preliminary experiments were
      performed on fluids with conductivity at 0.224 S/m. Particle trapping and
      micropumping were demonstrated at low voltages, reaching approximately 100
      microm/s for no more than 8 Vrms at 200 kHz. The fluid velocity was found to
      depend on the applied voltage as V(4), and the maxima were observed to be
      approximately 20 microm above the electrodes.

PMID- 17506596
TI  - Contractility of retinal pericytes grown on silicone elastomer substrates is
      through a protein kinase A-mediated intracellular pathway in response to
      vasoactive peptides.
AB  - The normal function of retinal capillaries to distribute blood within the retina
      depends on appropriate contractility of retinal pericytes, which is thought to be
      modulated by agents that alter intracellular cyclic adenosine-3'-monophosphate
      (cAMP) levels. We examined the hypothesis that the vasoactive peptides Vasoactive
      Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase Activating Peptide
      (PACAP) reduce pericyte contractility via a protein kinase A (PKA)-mediated
      intracellular pathway that utilises cAMP. We utilised a single-call assay of
      contractility that is based on visualising the contractile force exerted by the
      pericytes on a silicone elastomer substrate and quantified, as a contractility
      index, from the number and length of wrinkles induced in the silicone elastomer
      by the pericytes. Pericytes were cultured from the retinas of freshly killed
      abattoir cattle, and identified in culture using immunohistochemical techniques.
      The pericytes contracted in response to norepinephrine (EC(50)=8 microM) and
      relaxed in response to both VIP (EC(50)=48 nM) and PACAP (EC(50)=3 nM). The
      relaxation induced by PACAP was inhibited by Rp-cAMPS (EC(50)=26 microM), which
      is an agent that inhibits cAMP binding at PKA. We confirmed the activation of PKA
      by PACAP in experiments where H89 also inhibited the PACAP-induced relaxation.
      U71322, which inhibits phospholipase C-linked events, was also able to inhibit
      the PACAP-induced pericyte relaxation. Our results support the hypothesis that
      PACAP leads to the relaxation of pericytes via a PKA-mediated intracellular
      pathway and a phospholipase C-mediated pathway, which probably relies on
      hyperpolarisation because of activation of Ca(2+)-dependent potassium channels.
      This single-cell assay has proved useful as the basis for the development of a
      diagnostic procedure for diabetic retinopathy, which is an eye disease caused by
      abnormal regulation of blood flow in the retinal capillaries.

PMID- 17506597
TI  - Quality of drug treatment of childhood persistent asthma in Maryland medicaid
      recipients in transition from managed fee for service to managed capitation.
AB  - BACKGROUND: From December 1991 to June 1997, approximately 80% of Maryland's
      Medicaid recipients were served through a fee-for-service (FFS) managed care
      delivery system in which assigned primary care providers served as gatekeepers
      for hospital and specialty services. The remaining 20% of recipients were
      voluntarily enrolled in 1 of 5 available health maintenance organizations (HMOs).
      Beginning in June 1997, Maryland required most Medicaid recipients to enroll in
      capitated managed care organizations (MCOs), also referred to as managed Medicaid
      plans. Although research has been conducted on the quality of asthma care among
      MCOs and in MCOs for Medicaid versus non-Medicaid members, the quality of asthma
      care has been less well studied for MCO patients than for FFS patients.
      OBJECTIVE: To determine whether quality of drug use among Medicaid children with
      persistent asthma was different after the transition from the managed care FFS
      system to a capitated managed Medicaid system. METHODS: This 4-year retrospective
      cohort study (from June 1, 1996, to December 31, 2000) followed children aged 5
      to 18 years with persistent asthma (defined by the existence of at least 1
      medical claim with an International Classification of Diseases, Ninth Revision,
      Clinical Modification diagnosis code of 493.x and receipt of 2 or more pharmacy
      claims for beta2-agonists in a 6-month period) enrolled in Maryland Medicaid as
      they transitioned from the managed FFS system to 1 of 4 large capitated MCOs.
      Children were selected from a review of Medicaid enrollment records and medical
      and pharmacy FFS claims filed between June 1, 1996, and December 31, 1997.
      Children with a diagnosis of cystic fibrosis were excluded. The asthma quality
      indicator was defined as the proportion of children with persistent asthma (who
      had 2 or more claims for any short-acting beta2-agonists [SABAs], including
      metered-dose inhalers, nebulizers, or oral forms, which we defined as rescue
      medication, within a 6-month period), who also had at least 1 claim for a
      controller medication (inhaled corticosteroid, mastcell stabilizer, or
      leukotriene-receptor modifier) in the same 6-month period. Subjects were followed
      from June 1, 1996 (or, if later, the first Medicaid eligibility date), through
      December 31, 2000 (or, if earlier, the last Medicaid eligibility date). Mean
      quality indicator rates were calculated for the 2 managed FFS periods (FFS1 and
      FFS2) and the 6 managed Medicaid 6-month periods. We used generalized estimating
      equations to test for significant trends over time and to compare changes in the
      quality indicator in the managed Medicaid plans. RESULTS: There were 3,721
      children who met the inclusion and exclusion criteria for the study. The quality
      indicator (proportion of patients who received a controller medication among
      those receiving SABAs for asthma) was 62% in managed FFS1 and 57% in managed
      FFS2. In the first 6 months of managed Medicaid plans, the quality indicator rose
      from 56% to 57%, 59%, 61%, 66%, and 59% in the ensuing five 6-month observation
      periods. The results from the generalized estimating equations suggested slight
      improvement in the quality indicator in the managed Medicaid plans, but the
      difference was not significant (relative risk 1.01, 95% confidence interval, 0.95
      1.08). There was no significant trend in the asthma quality indicator over time
      in the managed Medicaid plans. CONCLUSION: There was no distinct improvement or
      worsening in asthma care as measured by the quality indicator (proportion of
      patients who received a controller medication among those receiving SABAs for
      asthma) as children moved from managed FFS to managed Medicaid. Larger sample
      sizes with no data loss may have produced a different result.

PMID- 17506598
TI  - Comprehensive coronary artery disease care in a safety-net hospital: results of
      Get With The Guidelines quality improvement initiative.
AB  - BACKGROUND: Adherence to published coronary artery disease (CAD) guidelines is
      suboptimal, particularly among minorities and the poor. While hospital-based
      quality-improvement programs may increase the use of evidence-based therapies,
      little data exist regarding the impact of such programs in sociodemographically
      disadvantaged (vulnerable) populations. Vulnerable patients in the United States
      are cared for primarily within the safety-net health system, which comprises
      urban public hospitals and outpatient community health centers. Denver Health is
      an example of an integrated system that encompasses both types of facilities.
      OBJECTIVE: To assess evidence-based medication use in CAD patients after
      initiation of an inpatient quality-improvement program at Denver Health. METHODS:
      We reviewed the medical records of 499 patients with angiographically proven CAD
      who were hospitalized between July 1998 and December 2002. Patients were
      prospectively identified through a multidisciplinary intervention led by a nurse
      manager, and their records were input retrospectively into the American Heart
      Association's Get With The Guidelines patient management tool. The association's
      program, which recommends initiating 4 cardioprotective drug classes while
      patients are hospitalized, was started 2 years into the observation period
      (August 2000). Treatment rates were compared over the ensuing years. We evaluated
      temporal trends in discharge use of 4 drugs: (1) betablockers, (2) angiotensin
      converting enzyme inhibitors (ACEIs), (3) hydroxymethylglutaryl coenzyme A
      reductase inhibitors (statins), and (4) aspirin. We calculated the proportion of
      eligible patients (no documented contraindication) who were prescribed each drug
      category as well as the proportion who received all 4 drug categories, our
      principal composite outcome. If any one drug was absent, the composite criterion
      was considered unmet. RESULTS: We observed progressive improvement in discharge
      use of the 4- drug composite: 18% in 1998-1999 (95% confidence interval [CI], 12%
      25%), 50% in 2000 (95% CI, 37%-63%), 62% (95% CI, 54%-70%) in 2001, and 72% (65%
      79%) in 2002 (P <0.001 for between-year differences). Among eligible patients
      discharged in 2002, 90% received beta-blockers, 91% received ACEIs, 86% received
      statins, and 93% received aspirin. CONCLUSIONS: Implementation of a
      multidisciplinary program led by a nurse manager was associated with increased
      CAD guideline compliance among sociodemographically disadvantaged patients. This
      compliance exceeded national averages. Achievement of the composite measure of
      use of all 4 recommended drug categories at discharge improved from 18% in 1998
      1999 to 72% in 2002.

PMID- 17506599
TI  - Pharmacoeconomic analysis of clopidogrel in secondary prevention of coronary
      artery disease.
AB  - BACKGROUND: When used as an alternative to or in addition to aspirin, clopidogrel
      has been demonstrated by some but not all randomized controlled trials to be
      effective in secondary prevention of cardiovascular (CV) events in patients with
      (1) coronary artery disease (CAD), (2) acute coronary syndrome (ACS), and (3)
      coronary stent placement. However, a drawback to clopidogrel therapy is the cost
      to patients and the health care system. Clinical studies have also demonstrated
      that when clopidogrel is used in addition to aspirin, the combination has an
      increased bleeding risk compared with aspirin alone. Cost-effectiveness analysis
      may aid in developing strategies for optimal use of clopidogrel. OBJECTIVE: To
      review and evaluate published pharmacoeconomic analyses on the use of clopidogrel
      in secondary prevention of CV events in patients who have known CAD, have ACS, or
      are undergoing percutaneous coronary interventions (PCIs). METHODS: English
      language peer-reviewed articles or abstracts were identified from MEDLINE and the
      Current Contents database (both from 1966 to August 15, 2006) using the search
      terms clopidogrel and pharmacoeconomics or clopidogrel and cost analyses.
      Citations from available articles were also reviewed for additional references.
      RESULTS: Multiple cost-effectiveness analyses of clopidogrel were available for
      review. These pharmacoeconomic studies were performed using different clinical
      databases from randomized controlled trials as well as observational databases.
      Cost was from the perspective of different health care systems and society; it
      was expressed in varying cost-effectiveness terms (life-year gained vs. per
      quality-adjusted life-year [QALY]). Although direct comparison among studies was
      difficult, clopidogrel appeared to be cost effective when used for up to 12
      months in combination with aspirin (compared with aspirin alone) in patients with
      ACS or in those undergoing PCIs, using different societal perspectives (both in
      the United States [average U.S.$15,000 per QALY among U.S. studies reporting per
      QALY] and in European countries [United Kingdom reported 18,888 pounds (average
      U.S.$28,300) per QALY]). In contrast, when used as an alternative to aspirin for
      secondary prevention of CAD, clopidogrel had mixed results in cost-effectiveness
      analyses (results varied from U.S.$25,000 to $114,000 per QALY). A major
      limitation of the models cited is the extrapolation of outcomes far beyond the
      duration used in the clinical trial database. CONCLUSION: On the basis of current
      cost-effectiveness data, clopidogrel should be used in addition to aspirin
      therapy for up to 12 months in all patients with non-ST elevation ACS as well as
      in those who received coronary stents. For secondary prevention of CAD,
      clopidogrel should be used only in those who cannot tolerate aspirin therapy.

PMID- 17506600
TI  - Observational study of the prevalence of febrile neutropenia in patients who
      received filgrastim or pegfilgrastim associated with 3-4 week chemotherapy
      regimens in community oncology practices.
AB  - BACKGROUND: Colony-stimulating factors (CSFs) significantly decrease the risk of
      febrile neutropenia (FN), a common complication of myelosuppressive chemotherapy.
      Pegfilgrastim (6 mg), introduced in 2002, has a sustained duration of action,
      with a single dose comparable in efficacy to daily injections of filgrastim (5 g
      per kg per day) for 10 to 11 days; both agents should be initiated 24 hours after
      completing chemotherapy. OBJECTIVES: To (1) describe the use of pegfilgrastim and
      filgrastim in oncology practices throughout the United States and (2) compare
      their effectiveness in actual practice as measured by the outcome of febrile
      neutropenia in patients who received chemotherapy regimens administered every 3
      to 4 weeks for breast, lung, ovarian, colon cancer, or lymphoma and who received
      a CSF prior to developing FN. METHODS: Data were retrospectively obtained from
      the medical records of a cohort of adult patients aged 18 years or older treated
      in 99 community oncology practices in the United States in 2001 and 2003.
      Eligible patients were treated with chemotherapy every 3 to 4 weeks for breast,
      lung, ovarian, colon cancer, or lymphoma and were users of filgrastim in 2001
      (prior to the U.S. Food and Drug Administration approval of pegfilgrastim in
      January 2002) or users of either filgrastim or pegfilgrastim or both CSF agents
      in 2003. RESULTS: Pegfilgrastim was initiated, on average, 2.4 days (SD +/-3.2)
      after chemotherapy in the first cycle of use and 1.9 (+/-3.0) days in subsequent
      cycles of use. In contrast, filgrastim was started on average 7.7 (+/-6.5) days
      and 4.9 (4.6) days after chemotherapy in the first and subsequent cycles of use
      in 2001, increasing to 9.6 (+/-6.2) and 6.4 (+/-6.4) days in 2003. In the first
      cycle of CSF use, filgrastim was administered for an average of 5.2 (+/-3.5) days
      to 583 patients in 2001 and 3.7 (+/-2.8) days to 868 patients in 2003 (P <0.001).
      Among patients who received more than 1 cycle of filgrastim (n = 457 in 2001 and
      n = 489 in 2003; 78.4% and 56.3% of filgrastim users, respectively), the mean
      days of filgrastim administered in subsequent cycles was 6.0 (+/-3.5) in 2001 and
      4.6 (+/-3.2) in 2003. Pegfilgrastim was administered as a single dose per
      chemotherapy course to 1,412 patients in 2003. Patients who received
      pegfilgrastim were more likely to have at least 1 myelosuppressive drug (74.8%)
      in the regimen compared with patients who received filgrastim in 2003 (70.0%, P =
      0.013), but a greater proportion of filgrastim patients in 2003 (19.4%) had
      advanced-stage disease compared with pegfilgrastim patients (14.8%, P = 0.005).
      More patients who received filgrastim in 2003 (36.2%) had a cancer other than
      breast cancer or non-Hodgkin's lymphoma compared with those who received
      pegfilgrastim (29.5%, P = 0.001). A total of 94 of 1,451 patients (6.5%) who
      received filgrastim experienced FN compared with 67 of 1,412 patients (4.7%) for
      pegfilgrastim. The odds ratio of developing FN among patients who received
      filgrastim versus pegfilgrastim was 1.41 (95% confidence interval, 1.02-1.96; P =
      0.040) after adjusting for patient and chemotherapy regimen characteristics.
      CONCLUSION: In this retrospective study of patients treated in 99 community
      oncology practices, patients who received filgrastim often initiated treatment
      later than recommended and received fewer days per cycle than demonstrated to be
      effective in randomized controlled trials. Pegfilgrastim was generally initiated
      earlier within the course of chemotherapy compared with filgrastim, and because
      of its sustained duration of action, only a single injection was required. In
      these patients treated with a heterogeneous group of chemotherapy regimens with a
      broad range of risk of FN, overall, an absolute 1.8% increase in the incidence of
      developing FN was observed in patients who received filgrastim compared with
      patients who received pegfilgrastim, (absolute rates of 6.5% and 4.7%,
      respectively).

PMID- 17506601
TI  - Administrative claims analysis of utilization and costs of care in health plan
      members with atopic dermatitis who had prior use of a topical corticosteroid and
      who initiate therapy with pimecrolimus or tacrolimus.
AB  - BACKGROUND: In the United States, pimecrolimus cream and tacrolimus ointment are
      approved as second-line therapy for short-term and intermittent noncontinuous
      long-term treatment of atopic dermatitis (AD) in nonimmunocompromised patients
      aged 2 years or older who have failed to respond adequately to other topical
      prescription treatments (e.g., topical corticosteroids), or when those treatments
      are not advisable; pimecrolimus is indicated for mild to- moderate AD and
      tacrolimus for moderate-to-severe AD. Comparative data on the effects of
      pimecrolimus versus tacrolimus on AD-related health care utilization and costs
      among similar patients seen in typical clinical practice are currently
      unavailable. OBJECTIVE: To compare utilization and costs of AD-related medical
      care in health plan members with AD who had prior use of a topical corticosteroid
      and who subsequently initiate therapy with pimecrolimus cream or tacrolimus
      ointment. METHODS: This was an observational, retrospective study using an
      administrative claims database with dates of service from August 1, 2000, through
      October 31, 2003, and representing approximately 2.5 million members in health
      maintenance organizations, preferred provider organizations, and Medicare and
      Medicaid plans mostly located in the cities of Chicago, Kansas City, and Phoenix
      and in the states of Kentucky, Florida, and Texas. The study sample included all
      members with 1 or more pharmacy claims for a topical corticosteroid and a
      diagnosis of AD (International Classification of Diseases, Ninth Revision,
      Clinical Modification [ICD-9-CM] code 691.XX (excluding 691.0X), or 692.XX
      (excluding 692.0X-692.8X)] who subsequently had 1 or more pharmacy claims for
      pimecrolimus or tacrolimus. AD-related utilization and medical care costs (plan
      payments plus member cost share) over 12 months of follow-up were compared
      between the pimecrolimus and tacrolimus groups. Because information on disease
      severity was not available in the administrative claims data, propensity matching
      was used to control for differences between groups in baseline demographic and
      clinical characteristics and pretreatment utilization of AD-related medical care
      services. RESULTS: Before matching, compared with the tacrolimus group (n = 197),
      members in the pimecrolimus group (n = 197) were older (mean age of 38 vs. 32
      years, P = 0.022), had fewer topical corticosteroid pharmacy claims (mean 2.08
      vs. 3.01, P = 0.002), and had fewer grams of corticosteroids dispensed (mean 132
      vs. 193, P = 0.029) in the 12 months prior to treatment. After matching, there
      were 157 members in each group with no statistically significant differences in
      pretreatment characteristics. During the 12-month follow-up period, the mean
      (median) number of pharmacy claims was 1.8 (1.0) for pimecrolimus versus 2.0
      (1.0) for tacrolimus and the mean (median) grams of study medication were 102
      (60) and 105 (60), respectively. Members in the pimecrolimus group received a
      lower average number of prescriptions for any topical corticosteroids (1.37 vs.
      2.04, P = 0.021) and for high-potency topical corticosteroids (0.61 vs. 1.04, P =
      0.023) and were less likely to initiate alternative therapy (5% vs. 17%, P
      <0.001) or receive antistaphylococcal antibiotics (16% vs. 27%, P = 0.014).
      Members in the pimecrolimus group had lower average (median) AD-related
      expenditures (75% to 78% attributable to AD drug cost) compared with matched
      tacrolimus members ($263 [$270] vs. $361 [$398], P = 0.012). CONCLUSIONS: In
      health plan members with AD who had previously received at least 1 topical
      corticosteroid prescription, the customary use of pimecrolimus or tacrolimus was
      1 to 2 prescriptions in 12 months of followup and only a median of 60 grams of
      topical medication. The difference in AD-related utilization and costs between
      pimecrolimus and tacrolimus was small, less than $100 per year, but favored
      pimecrolimus. Further research using validated measures of disease severity to
      control for potential confounding is needed to confirm the results of this
      observational study.

PMID- 17506602
TI  - Opinions regarding the Academy of Managed Care Pharmacy dossier submission
      guidelines: results of a small survey of managed care organizations and
      pharmaceutical manufacturers.
AB  - BACKGROUND: In recent years, there has been more emphasis on determining the
      total value of a drug product, which includes safety and efficacy information and
      clinical and economic value relative to other therapies. The Academy of Managed
      Care Pharmacy (AMCP) Format for Formulary Submissions was intended as a tool to
      assist health care providers in evaluating and selecting drug products.
      OBJECTIVE: The purpose of this research was to gain the perspectives of a sample
      of managed care organizations (MCOs) and pharmaceutical manufacturers regarding
      the AMCP Format submission and evaluation process, as well as their comments on
      possible future direction for these guidelines as an important part of the
      formulary decision-making process. METHODS: A random sample of large (>1 million
      lives) and small (<1 million lives) MCOs was generated using telephone numbers
      from the National Directory of Managed Care Organizations' database.
      Pharmaceutical manufacturer respondents were identified from the Pharmaceutical
      Research and Manufacturers of America (PhRMA) Foundation's Health Outcomes
      Committee. Telephone interviews were conducted by 2 researchers between September
      2004 and October 2005. Respondents from both pharmaceutical manufacturers and
      MCOs nationwide were familiar with the AMCP dossier preparation and review
      process, allowing us to compare perspectives from each group. The interview was
      designed to assess the following key areas: economic models, organizational
      burden, confidentiality, overall value, and future expectations. RESULTS:
      Representatives from 20 MCOs and 7 pharmaceutical manufacturers completed the
      interview; 21 MCO representatives refused to participate, citing company policy.
      Nearly all (87.5%) of the MCO personnel contacted reviewed dossiers within their
      organization. However, MCO respondents indicated that only 40% of all drugs they
      reviewed included dossiers from the manufacturers. For drug evaluation at the
      level of the pharmacy and therapeutics committee, we found that drugs were
      compared with a variety of products, with 11 respondents reporting comparisons
      with a placebo, and all respondents reporting a comparison with at least 1 other
      branded product. On average, 53.5% of the dossiers MCOs received included budget
      impact models, and 39.3% included cost-effectiveness analyses (CEAs) or cost
      benefit analyses. Of the dossiers with economic models, less than half (46.2%)
      were deemed adequate. Nearly two thirds of MCO respondents reported that they
      modified the provided model with their own population statistics, as many
      reported that manufacturers do not make models directly applicable to their
      health plan population. The perspectives of the pharmaceutical manufacturers
      varied dramatically from the MCO respondents with regard to the inclusion of
      economic models. Five of the 7 respondents indicated that their companies always
      included an economic model in the submitted dossiers. One respondent indicated
      that 85% of company dossiers included models, and another reported that 50% of
      dossiers included CEA models. Both MCOs and pharmaceutical manufacturers
      commented that organizational burden was high, with 70% of both groups reporting
      the use of outside consultants to assist in the dossier process. CONCLUSIONS:
      Overall, findings for this study suggest that awareness of the AMCP Format is
      high among MCOs and pharmaceutical manufacturers, but aligning objectives between
      the 2 organization types is necessary. Conceptually, proving a drug value beyond
      what the U.S. Food and Drug Administration requires is a reasonable request,
      something most respondents agreed on. However, less than half of all drugs
      reviewed had a dossier. In contrast to MCO respondents, pharmaceutical
      manufacturers appear to have a more positive outlook on the role of the AMCP
      Format in effectively communicating the value of a new drug product. Further
      steps need to be taken to improve acceptance and integration of the AMCP Format.

PMID- 17506605
TI  - Human immunodeficiency virus type 1 drug resistance mutations in peripheral blood
      mononuclear cell proviral DNA among antiretroviral treatment-naive and treatment
      experienced patients from Pune, India.
AB  - The prevalence of HIV drug resistance (HIVDR) mutations in the HIV protease (PR)
      and reverse transcriptase (RT) genes was estimated from peripheral blood
      mononuclear cells (PBMCs) in a study population of 25 antiretroviral (ARV)
      therapy-naive and 50 ARV-experienced chronically infected patients from Pune
      city, Maharashtra State, western India. Of the 75 study HIV-1 sequences, 73
      belonged to subtype C and 2 to subtype A1. On phylogenetic analysis, the study
      subtype C sequences sub clustered randomly with different Indian and non-Indian
      subtype C sequences, emphasizing the HIV-1 subtype C pol gene diversity. The
      heterosexual route was the most common route of transmission (74.67%). There were
      no observable HIVDR mutations in ARV-naive patients. The ARV-experienced patients
      had a history of exposure to nucleoside reverse transcriptase inhibitor and
      nonnucleoside reverse transcriptase inhibitor combinations. At least one HIVDR
      mutation in RT was observed in 29 (80.55%) of ARV-experienced patients with
      evidence of failing therapy. M184V was the most common observed HIVDR mutation.
      No PR major mutations were observed among ARV-experienced patients. A higher
      prevalence of proviral HIVDR mutations in PBMCs was associated with irregular
      adherence to therapy (p < 0.05) and HIV-1 RNA levels > 1000 copies/ml (p <
      0.001).

PMID- 17506606
TI  - The close relationship between South African and Latin American HTLV type 1
      strains corroborated in a molecular epidemiological study of the HTLV type 1
      isolates from a blood donor cohort.
AB  - It has been difficult to explain why all HTLV-1 sequences in Salvador, a city in
      the northeast of Brazil, belong to the Transcontinental (A) subgroup of the
      Cosmopolitan (a) subtype, since according to historical data the vast majority of
      slaves brought to Brazil (through Salvador) came from west Africa, where only the
      western African subgroup (C) has been found. To shed more light on this subject
      we conducted a phylogenetic analysis of 23 isolates from blood donors of
      Salvador. DNA was extracted and submitted to a nested PCR for amplification of
      the entire LTR region. The PCR products were purified and sequenced on an
      automated sequencer. Neighbor-joining and maximum likelihood phylogenetic
      analyses were performed. None of the new sequences from Salvador clustered within
      the West-African subgroup C. Confirming previous results, all sequences belonged
      to the Transcontinental subgroup (A) of the Cosmopolitan subtype, and clustered
      in two Latin American clusters. In addition we showed sequences from southern
      Africa clustering in both Latin American clusters. One of the new sequences is
      ancestral to the larger Latin American cluster beta due to a duplication of a 12
      bp long fragment, a finding that has not been previously described. These
      findings support the hypothesis that HTLV-1 isolates circulating in Latin America
      have a closer relationship to South African compared to West-African HTLV-1
      strains. The 12-bp-long duplications in one of the sequences has no obvious
      clinical or biological implications yet.

PMID- 17506607
TI  - Paradoxical effects of two theta-defensins on HIV type 1 infection.
AB  - Retrocyclin-1 (RC-100) is a cyclic octadecapeptide whose primary structure is
      based on the sequence of an expressed human theta-defensin pseudogene. RC-111 has
      the same amino acid sequence as RC-100 and is also cyclic, but its residues are
      placed in reverse order along the peptide's backbone. We quantified the effects
      of RC-100 and RC-111 on HIV-1 infection using HIV clones that expressed green
      fluorescent protein. Whereas 0.2 microg/ml of RC-100 inhibited infection of CD4
      positive cells by approximately 80%, its retro-analogue significantly enhanced
      infection of the cells. RC-100 and RC-111 also demonstrate their effects in HIV
      infection of CD4-negative cells. Whereas 40 ng/ml of RC-111 significantly
      enhanced infection of CD4-negative cells by HIV-1, RC-100 demonstrated
      significant inhibition of HIV infection with a concentration of approximately 10
      microg/ml. RC-111ox, an acyclic variant of RC-111 with a beta-hairpin structure,
      also enhanced HIV-1 infection, but did so less effectively than cyclic RC-111.
      The divergent actions of RC-100 and RC-111 show that topology and polarity of
      theta-defensin peptides can determine their effect on HIV infection. The ability
      of RC-111 to enhance HIV-1 infection might prove useful in developing peptides
      that can enhance gene delivery by HIV-based lentiviral vectors.

PMID- 17506608
TI  - Phenotypic variation in myocardial macrophage populations suggests a role for
      macrophage activation in SIV-associated cardiac disease.
AB  - Cardiac abnormalities are common in HIV-infected individuals, and have been
      especially well documented as contributors to mortality in HIV-infected children.
      Underlying pathogenetic mechanisms responsible for myocardial disease in HIV
      infection remain imperfectly understood. SIV-infected rhesus monkeys develop a
      spectrum of cardiac lesions similar to those seen in HIV-infected people,
      providing an important model for pathogenesis studies. Retrospective analysis of
      cardiac tissue collected at necropsy from SIV-infected rhesus monkeys was
      performed to evaluate myocardial macrophage and dendritic cell populations as a
      function of previously quantitated lymphocytic inflammatory infiltrates and
      cardiomyocyte degeneration or necrosis. Variations in the size and phenotype of
      macrophage and dendritic cell populations were examined as possible contributors
      to the pathogenesis of SIV-associated inflammatory lesions. Macrophages labeling
      immunohistochemically for CD163 differed substantially from macrophages labeling
      for HAM56 in overall number, distribution across groups, involvement in
      inflammatory clusters, correlation with the DC-SIGN(+) subpopulation of
      macrophages, and correlation with numbers of SIV-infected cells. CD163(+)
      macrophages occurred in significantly higher numbers in uninflamed hearts from
      SIV-infected animals than in hearts from SIV-infected animals with myocarditis or
      uninfected controls (p < 0.01). Numbers of CD163(+) cells correlated positively
      with numbers of SIV-infected cells (p < 0.05) suggesting that the CD163(+)
      population was associated with decreased inflammatory infiltration and reduced
      control of virus within the heart. As CD163 has been associated with nonclassical
      macrophage activation and an antiinflammatory phenotype, these results suggest
      that a balance between classical and nonclassical activation may affect levels of
      inflammatory infiltration and of myocardial virus burden.

PMID- 17506609
TI  - Hepatitis B virus genotype distribution and its lamivudine-resistant mutants in
      HIV-coinfected patients with chronic and occult hepatitis B.
AB  - Hepatitis B virus (HBV) genotypes were examined in HIV-infected patients with
      chronic and occult HBV infection. From a total population of 593 HIV-infected
      patients, 22 individuals (prevalence 3.7%) were found to be HBsAg while 72
      (12.1%) were found to be anti-HBc alone. From them, 20 and 4 were HBV DNA
      positive, respectively. These last four patients are therefore considered to be
      HBV infected in an occult form. The genotypes could be determined in all 24 HBV
      infected patients. HBV-A was the most common (20/24; 83.3%), followed by HBV-D
      (2/24; 8.3%) and HBV-F (1/24; 4.2%). The remaining sample exhibited mixed
      infection involving genotypes A and D as pure ones, thus also forming part of
      three intergenotypic recombinant forms exhibiting different mosaic S gene
      patterns. The sexual route of transmission was predominant among HBV genotype A
      infected patients. Among the 24 HBV DNA-positive patients, point mutations
      related to lamivudine resistance were found in four strains. These viral strains
      showed a methionine-to-valine substitution at codon 204 (rtM204V) in association
      with an upstream B-domain change at rtL180M. Additionally, two of them exhibited
      the additional rtV173L mutation. The value of HBV molecular monitoring including
      both HBV viral genomic characterization and genotypic resistance profile in HIV
      HBV-coinfected individuals is discussed.

PMID- 17506610
TI  - Evaluation of aldrithiol-2-inactivated preparations of HIV type 1 subtypes A, B,
      and D as reagents to monitor T cell responses.
AB  - The development of HIV vaccines is an urgent priority and there is need to
      generate reagents representing multiple subtypes that can be used to screen HIV-1
      specific responses. We used Aldrithiol-2 (AT-2), a mild oxidizing reagent, to
      eliminate the infectivity of HIV while maintaining its structure and ability to
      be processed for presentation to T cells. Inactivated subtype A, B, and D viruses
      were evaluated for their ability to stimulate T cell responses in PBMC samples
      from 18 U.S. subjects infected with HIV-1 subtype B and 32 Ugandan subjects
      infected with subtypes A and D or recombinants AC and AD. Five HIV-1-negative
      samples were also analyzed. T cell responses to AT-2-inactivated viral isolates
      were monitored by interferon-gamma (IFN-gamma) intracellular cytokine secretion
      (ICS) analysis; matched microvesicle preparations served as negative controls.
      Among the 18 subtype B infected subjects, 39% had CD3(+) CD4 (+) IFN-gamma
      responses and 67% had CD3(+) CD8(+) IFN-gamma responses. Of the 32 Ugandan
      subjects, 34% demonstrated CD3(+) CD4(+) IFN-gamma responses and 78% demonstrated
      CD3(+) CD8(+) IFN-gamma responses. Both subtype-specific and cross-reactive
      responses were observed. Responses to the AT-2 viruses tended to be lower in
      magnitude than those detected by a set of overlapping gag peptides. Robust
      lymphoproliferative responses to AT-2 viruses were seen in a subset of subjects.
      In conclusion, AT-2-inactivated HIV-1 virions stimulated both CD4 and CD8 HIV-1
      specific responses and may provide an additional reagent for screening HIV-1
      specific responses in HIV seropositives and vaccinees.

PMID- 17506611
TI  - Short communication: Immune reconstitution after autologous peripheral blood stem
      cell transplantation in HIV-infected patients: might be better than expected?
AB  - We carried out a longitudinal study to analyze the immune recovery of four
      patients with aggressive HIV-associated lymphoma (HIV+ Ly+) treated with highly
      active antiretroviral therapy (HAART) and high-dose chemotherapy followed by
      autologous peripheral blood stem cell transplantation (ASCT). We also studied
      three control non-HIV-infected patients with lymphoma (HIV-Ly+) and six HIV
      patients on HAART without lymphoma (HIV+ Ly-). After 12 months of follow-up, the
      HIV HIV+Ly+ patients reached the pre-ASCT CD4+ levels, despite a transient
      decrease after the ASCT. All ASCT patients (HIV+Ly+ and HIV-Ly+) showed an
      increase in CD4+, CD4+ CD45RO+, and CD4+CD28+ T cells/microl. Although HIV+Ly+
      patients had values of CD4+, CD4+CD45RO+, and CD4+CD28+ T cells/microl lower than
      the HIV-Ly+ patients, their recovery rate over the 12 months after ASCT appeared
      to be better. HIV+Ly+ patients had higher pre-ASCT plasma IL-7 levels than HIV
      Ly+, however, these values decreased after ASCT. All ASCT patients showed a
      slight increase of TCR rearrangement excision circles (TRECs) and they did not
      have a different pattern of TREC evolution. We could not find differences between
      HIV+Ly+ patients 12 months after ASCT and HIV+Ly- in DNA-HIV (copies/10(6) cell).
      Overall, HIV+Ly+ patients showed an appropriate immune reconstitution 12 months
      after ASCT, and, interestingly, they had an amount of DNA-HIV copies similar to
      HIV+Ly- control patients in their CD4+ cells.

PMID- 17506618
TI  - Accelerated bonelike apatite growth on porous polymer/ceramic composite scaffolds
      in vitro.
AB  - Although biodegradable polymer/ceramic composite scaffolds can overcome the
      limitations of conventional ceramic bone substitutes, the osteogenic potential of
      these scaffolds needs to be further enhanced for efficient bone tissue
      engineering. In this study, bonelike apatite was efficiently coated onto the
      scaffold surface by using polymer/ceramic composite scaffolds instead of polymer
      scaffolds and by using an accelerated biomimetic process to enhance the
      osteogenic potential of the scaffold. The creation of bonelike, apatite-coated
      polymer scaffold was achieved by incubating the scaffolds in simulated body fluid
      (SBF). The apatite growth on porous poly(D,L-lactic-co-glycolic
      acid)/nanohydroxyapatite (PLGA/ HA) composite scaffolds was significantly faster
      than on porous PLGA scaffolds. In addition, the distribution of coated apatite
      was more uniform on PLGA/HA scaffolds than on PLGA scaffolds. After a 5-day
      incubation period, the mass of apatite coated onto PLGA/HA scaffolds incubated in
      5 x SBF was 2.3-fold higher than PLGA/HA scaffolds incubated in 1 x SBF.
      Furthermore, when the scaffolds were incubated in 5 x SBF for 5 days, the mass of
      apatite coated onto PLGA/HA scaffolds was 4.5-fold higher than PLGA scaffolds.
      These results indicate that the biomimetic apatite coating can be accelerated by
      using a polymer/ceramic composite scaffold and concentrated SBF. When seeded with
      osteoblasts, the apatite-coated PLGA/HA scaffolds exhibited significantly higher
      cell growth, alkaline phosphatase activity, and mineralization in vitro compared
      to the apatite-coated PLGA scaffolds. Therefore, the apatite-coated PLGA/HA
      scaffolds may provide enhanced osteogenic potential when used as scaffold for
      bone tissue engineering.

PMID- 17506634
TI  - Structure and mechanism of helicases and nucleic acid translocases.
AB  - Helicases and translocases are a ubiquitous, highly diverse group of proteins
      that perform an extraordinary variety of functions in cells. Consequently, this
      review sets out to define a nomenclature for these enzymes based on current
      knowledge of sequence, structure, and mechanism. Using previous definitions of
      helicase families as a basis, we delineate six superfamilies of enzymes, with
      examples of crystal structures where available, and discuss these structures in
      the context of biochemical data to outline our present understanding of helicase
      and translocase activity. As a result, each superfamily is subdivided, where
      appropriate, on the basis of mechanistic understanding, which we hope will
      provide a framework for classification of new superfamily members as they are
      discovered and characterized.

PMID- 17506635
TI  - Chemical evolution as a tool for molecular discovery.
AB  - In modern academic and industrial laboratories, evolutionary strategies are used
      routinely to identify biopolymers with novel activities. Large libraries of
      nucleic acids (approximately 10(15)) or peptides and proteins (approximately
      10(13)) can be subjected to multiple rounds of selective pressure, amplification,
      and diversification, yielding individual sequences with desirable properties.
      Although the evolutionary approach is a powerful search tool, the chemical nature
      of biopolymers is not suited for all purposes. Application of evolutionary
      strategies to libraries of arbitrary chemical composition would overcome this
      problem, and radically change traditional small-molecule discovery. The chemical
      make-up of in vitro evolution libraries has necessarily been limited, because
      library synthesis relies on enzymes. A great deal of current research focuses on
      expanding the chemical repertoire of in vitro evolution by (a) broadening enzyme
      substrate specificities to include unnatural building blocks, or (b) developing
      methods to translate DNA sequences into multistep organic syntheses. We discuss
      the strengths and weaknesses of the approaches, review the successes, and
      consider the future of chemical evolution as a tool.

PMID- 17506637
TI  - Discovery of G protein signaling.
AB  - The mechanism of transmembrane signaling by the receptor-activated adenylyl
      cyclase was an enigma. It was suggested that hydrolysis of GTP is a turn-off
      mechanism that resets the active adenylyl cyclase to the inactive state. To test
      this hypothesis, we developed a specific GTPase assay and found that the
      catecholamine adrenergic agonists stimulated the hydrolysis of GTP. To resolve
      the question of how the hormone concurrently stimulates GTP hydrolysis and
      activates the adenylyl cyclase, we suggested the regulatory GTPase cycle. Thus,
      because the hormone facilitates the binding of GTP, which is subsequently
      hydrolyzed, the regulatory cycle results in a hormone-stimulated GTPase activity.
      This model also predicts that two mechanisms could account for stimulation of
      adenylyl cyclase activity-either by the familiar hormone stimulation of the
      activation reaction or by an inhibition of the turn-off reaction. Indeed, we
      showed that cholera toxin enhances adenylyl cyclase activity by inhibition of GTP
      hydrolysis. Finally, we also showed that the hormone-activated receptor
      stimulates adenylyl cyclase activity by facilitating the exchange of bound GDP
      for free GTP. Thus, we presented, for the first time, an explicit mechanism for
      receptor action.

PMID- 17506638
TI  - Why do we still have a maternally inherited mitochondrial DNA? Insights from
      evolutionary medicine.
AB  - The human cell is a symbiosis of two life forms, the nucleus-cytosol and the
      mitochondrion. The nucleus-cytosol emphasizes structure and its genes are
      Mendelian, whereas the mitochondrion specializes in energy and its mitochondrial
      DNA (mtDNA) genes are maternal. Mitochondria oxidize calories via oxidative
      phosphorylation (OXPHOS) to generate a mitochondrial inner membrane proton
      gradient (DeltaP). DeltaP then acts as a source of potential energy to produce
      ATP, generate heat, regulate reactive oxygen species (ROS), and control
      apoptosis, etc. Interspecific comparisons of mtDNAs have revealed that the mtDNA
      retains a core set of electron and proton carrier genes for the proton
      translocating OXPHOS complexes I, III, IV, and V. Human mtDNA analysis has
      revealed these genes frequently contain region-specific adaptive polymorphisms.
      Therefore, the mtDNA with its energy controlling genes may have been retained to
      permit rapid adaptation to new environments.

PMID- 17506639
TI  - Structural biology of nucleocytoplasmic transport.
AB  - In eukaryotic cells, segregation of DNA replication and RNA biogenesis in the
      nucleus and protein synthesis in the cytoplasm poses the requirement of
      transporting thousands of macromolecules between the two cellular compartments.
      Transport between nucleus and cytoplasm is mediated by soluble receptors that
      recognize specific cargoes and carry them through the nuclear pore complex (NPC),
      the sole gateway between the two compartments at interphase. Nucleocytoplasmic
      transport is specific not only in terms of cargo recognition, but also in terms
      of directionality, with nuclear proteins imported into the nucleus and RNAs
      exported from it. How is directionality achieved? How can the receptors be both
      specific and versatile in recognizing a multitude of cargoes? And how can their
      interaction with NPCs allow fast translocation? We describe the molecular
      mechanisms underlying nucleocytoplasmic transport as they have been revealed by
      structural studies of the receptors and regulators in different steps of
      transport cycles.

PMID- 17506640
TI  - Modulation of the ryanodine receptor and intracellular calcium.
AB  - Ryanodine receptors (RyRs)/Ca2+ release channels, on the endoplasmic and
      sarcoplasmic reticulum of most cell types, are required for intracellular Ca2+
      release involved in diverse cellular functions, including muscle contraction and
      neurotransmitter release. The large cytoplasmic domain of the RyR serves as a
      scaffold for proteins that bind to and modulate the channel's function and that
      comprise a macromolecular signaling complex. These proteins include calstabins
      [FK506-binding proteins (FKBPs)], calmodulin (CaM), phosphodiesterase, kinases,
      phosphatases, and their cognate targeting proteins. This review focuses on recent
      progress in the understanding of RyR regulation and disease mechanisms that are
      associated with channel dysfunction.

PMID- 17506643
TI  - Molecular architecture of smell and taste in Drosophila.
AB  - The chemical senses-smell and taste-allow animals to evaluate and distinguish
      valuable food resources from dangerous substances in the environment. The central
      mechanisms by which the brain recognizes and discriminates attractive and
      repulsive odorants and tastants, and makes behavioral decisions accordingly, are
      not well understood in any organism. Recent molecular and neuroanatomical
      advances in Drosophila have produced a nearly complete picture of the peripheral
      neuroanatomy and function of smell and taste in this insect. Neurophysiological
      experiments have begun to provide insight into the mechanisms by which these
      animals process chemosensory cues. Given the considerable anatomical and
      functional homology in smell and taste pathways in all higher animals,
      experimental approaches in Drosophila will likely provide broad insights into the
      problem of sensory coding. Here we provide a critical review of the recent
      literature in this field and comment on likely future directions.

PMID- 17506642
TI  - Neuron-glial interactions in blood-brain barrier formation.
AB  - The blood brain barrier (BBB) evolved to preserve the microenvironment of the
      highly excitable neuronal cells to allow for action potential generation and
      propagation. Intricate molecular interactions between two main cell types, the
      neurons and the glial cells, form the underlying basis of the critical
      functioning of the nervous system across species. In invertebrates, interactions
      between neurons and glial cells are central in establishing a functional BBB.
      However, in vertebrates, the BBB formation and function is coordinated by
      interactions between neurons, glial cells, and endothelial cells. Here we review
      the neuron-glial interaction-based blood barriers in invertebrates and
      vertebrates and provide an evolutionary perspective as to how a glial-barrier
      system in invertebrates evolved into an endothelial barrier system. We also
      summarize the clinical relevance of the BBB as this protective barrier becomes
      disadvantageous in the pharmacological treatment of various neurological
      disorders.

PMID- 17506644
TI  - Why is Wallerian degeneration in the CNS so slow?
AB  - Wallerian degeneration (WD) is the set of molecular and cellular events by which
      degenerating axons and myelin are cleared after injury. Why WD is rapid and
      robust in the PNS but slow and incomplete in the CNS is a longstanding mystery.
      Here we review current work on the mechanisms of WD with an emphasis on
      deciphering this mystery and on understanding whether slow WD in the CNS could
      account for the failure of CNS axons to regenerate.

PMID- 17506641
TI  - Synapses: sites of cell recognition, adhesion, and functional specification.
AB  - Synapses are specialized adhesive contacts characteristic of many types of cell
      cell interactions involving neurons, immune cells, epithelial cells, and even
      pathogens and host cells. Cell-cell adhesion is mediated by structurally diverse
      classes of cell-surface glycoproteins, which form homophilic or heterophilic
      interactions across the intercellular space. Adhesion proteins bind to a
      cytoplasmic network of scaffolding proteins, regulators of the actin
      cytoskeleton, and signal transduction pathways that control the structural and
      functional organization of synapses. The themes of this review are to compare the
      organization of synapses in different cell types and to understand how different
      classes of cell adhesion proteins and cytoplasmic protein networks specify the
      assembly of functionally distinct synapses in different cell contexts.

PMID- 17506645
TI  - Neurobiology of feeding and energy expenditure.
AB  - Significant advancements have been made in the past century regarding the
      neuronal control of feeding behavior and energy expenditure. The effects and
      mechanisms of action of various peripheral metabolic signals on the brain have
      become clearer. Molecular and genetic tools for visualizing and manipulating
      individual components of brain homeostatic systems in combination with
      neuroanatomical, electrophysiological, behavioral, and pharmacological techniques
      have begun to elucidate the molecular and neuronal mechanisms of complex feeding
      behavior and energy expenditure. This review highlights some of these
      advancements that have led to the current understanding of the brain's
      involvement in the acute and chronic regulation of energy homeostasis.

PMID- 17506648
TI  - Elicitors, effectors, and R genes: the new paradigm and a lifetime supply of
      questions.
AB  - The plant basal immune system can detect broadly present microbe-associated
      molecular patterns (MAMPs, also called PAMPs) and induce defenses, but adapted
      microbes express a suite of effector proteins that often act to suppress these
      defenses. Plants have evolved other receptors (R proteins) that detect these
      pathogen effectors and activate strong defenses. Pathogens can subsequently alter
      or delete their recognized effectors to avoid defense elicitation, at risk of a
      fitness cost associated with loss of those effectors. Significant research
      progress is revealing, among other things, mechanisms of MAMP perception, the
      host defense processes and specific host proteins that pathogen effectors target,
      the mechanisms of R protein activation, and the ways in which pathogen effector
      suites and R genes evolve. These findings carry practical ramifications for
      resistance durability and for future resistance engineering. The present review
      uses numerous questions to help clarify what we know and to identify areas that
      are ripe for further investigation.

PMID- 17506652
TI  - Identifying microorganisms involved in specific pathogen suppression in soil.
AB  - Suppressive soils hold considerable potential for managing soilborne pathogens.
      When the suppressiveness has a biological origin, identifying the causal
      organisms is the crucial step in realizing this potential. Armed with such
      knowledge, it may be possible to develop effective and sustainable pest
      management strategies through application of these organisms or agronomic
      practices that influence their population densities. This chapter focuses on the
      development and utilization of a population-based approach for identifying
      microorganisms involved in specific pathogen suppression. Key experimental design
      principles of the approach are explored by examining experiments characterizing
      the biological nature of take-all decline. We also describe how this approach was
      used to identify microorganisms that suppress the sugarbeet cyst nematode.
      Additional experimental design considerations and future directions for such
      investigations are also discussed.

PMID- 17506654
TI  - Breast CT.
AB  - Breast cancer is a serious disease that accounts for approximately 40,000 deaths
      per year in the United States. Unfortunately, there is no known cause of breast
      cancer, and therefore the best way to prevent mortality is early detection. In
      the past 15 years, breast cancer mortality has been reduced significantly, which
      is in part due to screening with film-screen mammography. Nonetheless,
      conventional mammography lacks sensitivity, especially for certain subgroups of
      women such as those with dense breast tissue, those under 50 years old, and pre-
      or perimenopausal women. In addition, mammography has a very poor positive
      predictive value for biopsy, with 70%-90% of biopsies performed turning out
      negative. By improving visualization of breast tissue, X-ray computerized
      tomography (CT) of the breast can potentially provide improvements in diagnostic
      accuracy over conventional mammography. Owing to recent technological
      developments in digital detector technology, flat-panel CT imagers dedicated to
      imaging of the breast are now feasible. A number of academic groups are currently
      researching dedicated breast CT and prototype systems are currently being
      evaluated in the clinical setting.

PMID- 17506655
TI  - Injury biomechanics and child abuse.
AB  - Child abuse is a leading cause of morbidity and mortality in young children and
      infants in the United States. Medical care providers, social services, and legal
      systems make critical decisions regarding injury and history plausibility daily.
      Injury plausibility judgments rely on evidence-based medicine, individualized
      experiences, and empirical data. A poor outcome may result if abuse is missed or
      an innocent family is accused, therefore evidence and science-based injury
      assessments are required. Although research in biomechanics has improved clinical
      understanding of injuries in children, much work is still required to develop a
      more scientific, rigorous approach to assessing injury causation. This article
      reviews key issues in child abuse and how injury biomechanics research may help
      improve accuracy in differentiating abuse from accidental events. Case-based
      biomechanical investigations, human surrogate, and computer modeling biomechanics
      research applied to child abuse injury are discussed. The goal of this paper is
      to provide an overview of key research studies rather than on review or
      commentary articles. Limitations and future research needs are also reviewed.

PMID- 17506656
TI  - microRNAs in vertebrate physiology and human disease.
AB  - Over the past five years, the importance of a diverse class of 18-24 nucleotide
      RNA molecules, known as microRNAs (miRNAs) has increasingly been recognized.
      These highly conserved RNAs regulate the stability and translational efficiency
      of complementary target messenger RNAs. The human genome is now predicted to
      encode nearly 1,000 miRNAs that likely regulate at least one third of all human
      transcripts. Despite rapid progress in miRNA discovery, the physiologic functions
      of only a small number have been definitively established. In this review, we
      discuss the principles of miRNA function that have emerged from the studies
      performed thus far in vertebrates. We also discuss known and potential roles for
      miRNAs in human disease states and discuss the influence of human genetic
      variation on miRNA-mediated regulation.

PMID- 17506657
TI  - Congenital disorders of glycosylation: a rapidly expanding disease family.
AB  - Congenital disorders of glycosylation (CDG) are a large family of genetic
      diseases resulting from defects in the synthesis of glycans and in the attachment
      of glycans to other compounds. These disorders cause a wide range of human
      diseases, with examples emanating from all medical subspecialties. Since our 2001
      review on CDG ( 36 ), this field has seen substantial growth: The number of N
      glycosylation defects has doubled (from 6 to 12), five new O-glycosylation
      defects have been added to the two previously known ones, three combined N- and O
      glycosylation defects have been identified, the first lipid glycosylation defects
      have been discovered, and a new domain, that of the hyperglycosylation defects,
      has been introduced. A number of CDG are due to defects in enzymes with a
      putative glycosyltransferase function. There is also a growing group of patients
      with unidentified defects (CDG-x), some with typical clinical presentations and
      others with presentations not seen before in CDG. This review focuses on the
      clinical, biochemical, and genetic characteristics of CDG and on advances
      expected in their future study and clinical management.

PMID- 17506659
TI  - Annotating noncoding RNA genes.
AB  - Noncoding RNA genes produce a functional RNA product rather than a translated
      protein. More than 1500 homologs of known "classical" RNA genes can be annotated
      in the human genome sequence, and automatic homology-based methods predict up to
      5000 related sequences. Methods to predict novel RNA genes on a whole-genome
      scale are immature at present, but their use hints at tens of thousands of such
      genes in the human genome. Messenger RNA-like transcripts with no protein-coding
      potential are routinely discovered by high-throughput transcriptome analyses.
      Meanwhile, various experimental studies have suggested that the vast majority of
      the human genome is transcribed, although the proportion of the detected RNAs
      that is functional remains unknown.

PMID- 17506660
TI  - Multistage sampling for genetic studies.
AB  - In the past, to study Mendelian diseases, segregating families have been
      carefully ascertained for segregation analysis, followed by collecting extended
      multiplex families for linkage analysis. This would then be followed by
      association studies, using independent case-control samples and/or additional
      family data. Recently, for complex diseases, the initial sampling has been for a
      genome-wide linkage analysis, often using independent sib-pairs or nuclear
      families, to identify candidate regions for follow-up with association studies,
      again using case-control samples and/or additional family data. We now have the
      ability to conduct genome-wide association studies using 100,000-500,000
      diallelic genetic markers. For such studies we focus especially on efficient two
      stage association sampling designs, which can retain nearly optimal statistical
      power at about half the genotyping cost. Similarly, beginning an association
      study by genotyping pooled samples may also be a viable option if the cost of
      accurately pooling DNA samples outweighs genotyping costs. Finally, we note that
      the sampling of family data for linkage analysis is not a practice that should be
      automatically discontinued.

PMID- 17506661
TI  - Repetitive sequences in complex genomes: structure and evolution.
AB  - Eukaryotic genomes contain vast amounts of repetitive DNA derived from
      transposable elements (TEs). Large-scale sequencing of these genomes has produced
      an unprecedented wealth of information about the origin, diversity, and genomic
      impact of what was once thought to be "junk DNA." This has also led to the
      identification of two new classes of DNA transposons, Helitrons and Polintons, as
      well as several new superfamilies and thousands of new families. TEs are
      evolutionary precursors of many genes, including RAG1, which plays a role in the
      vertebrate immune system. They are also the driving force in the evolution of
      epigenetic regulation and have a long-term impact on genomic stability and
      evolution. Remnants of TEs appear to be overrepresented in transcription
      regulatory modules and other regions conserved among distantly related species,
      which may have implications for our understanding of their impact on speciation.

PMID- 17506662
TI  - Using genomics to study how chromatin influences gene expression.
AB  - A postgenome challenge is to understand how the code in DNA is converted into the
      biological processes underlying various cell fates. By establishing the
      appropriate technical tools, we are moving from an era in which such questions
      have been asked by studying individual genes to one in which large domains, whole
      chromosomes, and the entire human genome can be investigated. These developments
      will allow us to study in parallel the transcriptional program and components of
      the epigenetic program (nuclear position, timing of replication, chromatin
      structure and modification, DNA methylation) to determine the hierarchy and order
      of events required to switch genes on and off during differentiation and
      development.

PMID- 17506663
TI  - Regional fat deposition as a factor in FFA metabolism.
AB  - Humans have a large variability in body fat distribution, which has tremendous
      implications for metabolic health. Obese individuals with an upper-body-fat
      distribution have increased health complications such as dyslipidemia,
      hypertension, insulin resistance, and type 2 diabetes in comparison with lower
      body-obese individuals. Additionally, females have more body fat, a greater
      proportion of fat in their lower body, and much less visceral fat than do lean
      males at the same body mass index. The reasons for these differences in body fat
      distribution have not been clearly identified but could be important. Herein we
      review what has been learned about regional differences in triglyceride storage
      capacity and lipolysis as they relate to the causes and consequences of regional
      fat accumulation. Both sex and site differences in regional fat storage have been
      described. In contrast, with the exception of variations between men and women in
      the contribution of visceral adipose tissue to hepatic FFA delivery, most studies
      have failed to show important sex differences in regional lipolysis in vivo.

PMID- 17506666
TI  - Trace element transport in the mammary gland.
AB  - The mammary gland has a remarkable capacity to adapt to maternal deficiency or
      excess of iron, copper, and zinc and to homeostatically control milk
      concentrations of these essential nutrients. Similarly, it can regulate changes
      in concentrations of iron, copper, and zinc change during lactation. For iron,
      this regulation is achieved by transferrin receptor, DMT1, and ferroportin,
      whereas mammary gland copper metabolism is regulated by Ctr1, ATP7A, and ATP7B.
      Zinc homeostasis is complex, involving both zinc importers (Zip3) and zinc
      exporters (ZnT-1, ZnT-2, and ZnT-4). Both transcriptional and post-translational
      regulation can affect protein abundance and cellular localization of these
      transporters, finely orchestrating uptake, intracellular trafficking, and
      secretion of iron, copper, and zinc. The control of mammary gland uptake and milk
      secretion of iron, copper, and zinc protects both the mammary gland and the
      breast-fed infant against deficiency and excess of these nutrients.

PMID- 17506667
TI  - Fifty-five-year personal experience with human nutrition worldwide.
AB  - By 1950 the vitamins had been identified, but little was known of their
      functions. Beriberi, pellagra, and ariboflavinosis were disappearing, but
      kwashiorkor and/or marasmus were common in most developing countries.
      Requirements for protein were still uncertain, and those for essential amino
      acids or essential fatty acids were unknown. The author's contributions in the
      field of vitamins began in the 1950s and have been reported in more than 650
      publications and in 20 books or monographs. These contributions include
      establishing the Institute of Nutrition of Central America and Panama, the
      Department of Nutrition and Food Science at the Massachusetts Institute of
      Technology, the World Hunger Program of the United Nations University, and the
      International Nutrition Foundation. His scientific contributions include
      identification of synergistic interactions of nutrition and infection, use of
      potassium iodate for fortifying crude moist salt, research in the epidemiology of
      kwashiorkor and marasmus, development of a successful low-cost protein-rich food
      for infants and young children, establishment of human protein requirements, and
      investigation of single-cell protein for food use.

PMID- 17506668
TI  - Postgenomic adventures with Rhodobacter sphaeroides.
AB  - This review describes some of the recent highlights taken from the studies of
      Rhodobacter sphaeroides 2.4.1. The review is not intended to be comprehensive,
      but to reflect the bias of the authors as to how the availability of a sequenced
      and annotated genome, a gene-chip, and proteomic profile as well as comparative
      genomic analyses can direct the progress of future research in this system.

PMID- 17506669
TI  - Protein secretion in gram-negative bacteria via the autotransporter pathway.
AB  - Autotransporters are a large and diverse superfamily of proteins produced by
      pathogenic gram-negative bacteria that are composed of an N-terminal passenger
      domain, which typically harbors a virulence function, and a C-terminal beta
      domain. It has long been known that the beta domain anchors the protein to the
      outer membrane and facilitates transport of the passenger domain into the
      extracellular space. Despite the apparent simplicity of the autotransporter
      pathway, several aspects of autotransporter biogenesis remain poorly understood,
      most notably the mechanism by which the passenger domain is translocated across
      the outer membrane. Here we review recent evidence that the enormous sequence
      diversity of both passenger and beta domains belies a remarkable conservation of
      structure. We also discuss insights into each stage of autotransporter biogenesis
      that have emerged from recent structural, biochemical, and imaging studies.

PMID- 17506670
TI  - Comparative genomics of protists: new insights into the evolution of eukaryotic
      signal transduction and gene regulation.
AB  - Data from protist genomes suggest that eukaryotes show enormous variability in
      their gene complements, especially of genes coding regulatory proteins. Overall
      counts of eukaryotic signaling proteins show weak nonlinear scaling with proteome
      size, but individual superfamilies of signaling domains might show vast
      expansions in certain protists. Alteration of domain architectural complexity of
      signaling proteins and repeated lineage-specific reshaping of architectures might
      have played a major role in the emergence of new signaling interactions in
      different eukaryotes. Lateral transfer of various signaling domains from bacteria
      or from hosts, in parasites such as apicomplexans, appears to also have played a
      major role in the origin of new functional networks. Lineage-specific expansion
      of regulatory proteins, particularly of transcription factors, has played a
      critical role in the adaptive radiation of different protist lineages.
      Comparative genomics allows objective reconstruction of the ancestral conditions
      and subsequent diversification of several regulatory systems involved in
      phosphorylation, cyclic nucleotide signaling, Ubiquitin conjugation, chromatin
      remodeling, and posttranscriptional gene silencing.

PMID- 17506671
TI  - The impact of genome analyses on our understanding of ammonia-oxidizing bacteria.
AB  - The availability of whole-genome sequences for ammonia-oxidizing bacteria (AOB)
      has led to dramatic increases in our understanding of these environmentally
      important microorganisms. Their genomes are smaller than many other members of
      the proteobacteria and may indicate genome reductions consistent with their
      limited lifestyle. The genomes have a surprising level of gene repetition
      including genes for ammonia catabolism, iron acquisition, and insertion
      sequences. The gene profiles reveal limited genes for catabolism and transport of
      complex organic compounds, but complete pathways for some other compounds. This
      led to the observation of chemolithoheterotrophic growth of Nitrosomonas
      europaea. Genes for sucrose synthesis/degradation were identified. The core
      metabolic module of aerobic ammonia oxidation, the extraction of electrons from
      hydroxylamine to generate proton-motive force and reductant, has evolutionary
      roots in the denitrification inventory of anaerobic sulfur-dependent bacteria.
      The extension by ammonia monooxygenase provides a mechanism to feed this module
      using ammonia and O(2).

PMID- 17506672
TI  - Nonhomologous end-joining in bacteria: a microbial perspective.
AB  - In eukaryotic cells, repair of DNA double-strand breaks (DSBs) by the
      nonhomologous end-joining (NHEJ) pathway is critical for genomic stability. A
      functionally homologous repair apparatus, composed of Ku and a multifunctional
      DNA ligase (LigD), has recently been identified in many prokaryotes. Eukaryotic
      organisms employ a large number of factors to repair breaks by NHEJ. In contrast,
      the bacterial NHEJ complex is a two-component system that, despite its relative
      simplicity, possesses all of the break-recognition, end-processing, and ligation
      activities required to facilitate the complex task of DSB repair. Here, we review
      recent discoveries on the structure and function of the bacterial NHEJ repair
      apparatus. In particular, we discuss the evolutionary origins of this DSB repair
      pathway, how the diverse activities within the prokaryotic end-joining complex
      cooperate to facilitate DSB repair, the physiological roles of bacterial NHEJ,
      and finally, the essential function of NHEJ in the life cycle of
      mycobacteriophage.

PMID- 17506673
TI  - Heterotrimeric G protein signaling in filamentous fungi.
AB  - Filamentous fungi are multicellular eukaryotic organisms known for nutrient
      recycling as well as for antibiotic and food production. This group of organisms
      also contains the most devastating plant pathogens and several important human
      pathogens. Since the first report of heterotrimeric G proteins in filamentous
      fungi in 1993, it has been demonstrated that G proteins are essential for growth,
      asexual and sexual development, and virulence in both animal and plant pathogenic
      filamentous species. Numerous G protein subunit and G protein-coupled receptor
      genes have been identified, many from whole-genome sequences. Several regulatory
      pathways have now been delineated, including those for nutrient sensing,
      pheromone response and mating, and pathogenesis. This review provides a
      comparative analysis of G protein pathways in several filamentous species, with
      discussion of both unifying themes and important unique signaling paradigms.

PMID- 17506674
TI  - Cytoskeletal elements in bacteria.
AB  - All cytoskeletal elements known from eukaryotic cells are also present in
      bacteria, where they perform vital tasks in many aspects of the physiology of the
      cell. Bacterial tubulin (FtsZ), actin (MreB), and intermediate filament (IF)
      proteins are key elements in cell division, chromosome and plasmid segregation,
      and maintenance of proper cell shape, as well as in maintenance of cell polarity
      and assembly of intracellular organelle-like structures. Although similar tasks
      are performed by eukaryotic cytoskeletal elements, the individual functions of
      FtsZ, MreBs, and IFs are different from those performed by their eukaryotic
      orthologs, revealing a striking evolutional plasticity of cytoskeletal proteins.
      However, similar to the functions of their eukaryotic counterparts, the functions
      conferred by bacterial cytoskeletal proteins are driven by their ability to form
      dynamic filamentous structures. Therefore, the cytoskeleton was a prokaryotic
      invention, and additional bacteria-specific cytoskeletal elements, such as fibril
      and MinD-type ATPases, that confer various functions in cell morphology and
      during the cell cycle have been observed in prokaryotes. The investigation of
      these elements will give fundamental information for all types of cells and can
      reveal the molecular mode of action of cytoskeletal, filament-forming proteins.

PMID- 17506679
TI  - Biofilm formation by plant-associated bacteria.
AB  - Plants support a diverse array of bacteria, including parasites, mutualists, and
      commensals on and around their roots, in the vasculature, and on aerial tissues.
      These microbes have a profound influence on plant health and productivity.
      Bacteria physically interact with surfaces to form complex multicellular and
      often multispecies assemblies, including biofilms and smaller aggregates. There
      is growing appreciation that the intensity, duration, and outcome of plant
      microbe interactions are significantly influenced by the conformation of adherent
      microbial populations. Biofilms on different tissues have unique properties,
      reflecting the prevailing conditions at those sites. Attachment is required for
      biofilm formation, and bacteria interact with plant tissues through adhesins
      including polysaccharides and surface proteins, with initial contact often
      mediated by active motility. Recognition between lectins and their cognate
      carbohydrates is a common means of specificity. Biofilm development and the
      resulting intimate interactions with plants often require cell-cell communication
      between colonizing bacteria.

PMID- 17506678
TI  - Morphogenesis in Candida albicans.
AB  - Candida albicans is termed a dimorphic fungus because it proliferates in either a
      yeast form or a hyphal form. The switch between these forms is the result of a
      complex interplay of external and internal factors and is coordinated in part by
      polarity-regulating proteins that are conserved among eukaryotic cells. However,
      yeast and hyphal cells are not the only morphological states of C. albicans. The
      opaque form required for mating, the pseudohyphal cell, and the chlamydospore
      represent distinct cell types that form in response to specific genetic or
      environmental conditions. In addition, hyperextended buds can form as a result of
      various cell cycle-related stresses. Recent studies are beginning to shed light
      on some of the molecular controls regulating the various morphogenetic forms of
      this fascinating human pathogen.

PMID- 17506680
TI  - Nitrogen regulation in bacteria and archaea.
AB  - A wide range of Bacteria and Archaea sense cellular 2-oxoglutarate (2OG) as an
      indicator of nitrogen limitation. 2OG sensor proteins are varied, but most of
      those studied belong to the PII superfamily. Within the PII superfamily, GlnB and
      GlnK represent a widespread family of homotrimeric proteins (GlnB-K) that bind
      and respond to 2OG and ATP. In some bacterial phyla, GlnB-K proteins are
      covalently modified, depending on enzymes that sense cellular glutamine as an
      indicator of nitrogen sufficiency. GlnB-K proteins are central clearing houses of
      nitrogen information and bind and modulate a variety of nitrogen assimilation
      regulators and enzymes. NifI(1) and NifI(2) comprise a second widespread family
      of PII proteins (NifI) that are heteromultimeric, respond to 2OG and ATP, and
      bind and regulate dinitrogenase in Euryarchaeota and many Bacteria.

PMID- 17506681
TI  - Lantibiotics: peptides of diverse structure and function.
AB  - The current need for antibiotics with novel target molecules has coincided with
      advances in technical approaches for the structural and functional analysis of
      the lantibiotics, which are ribosomally synthesized peptides produced by gram
      positive bacteria. These peptides have antibiotic or morphogenetic activity and
      are structurally defined by the presence of unusual amino acids introduced by
      posttranslational modification. Lantibiotics are complex polycyclic molecules
      formed by the dehydration of select Ser and Thr residues and the intramolecular
      addition of Cys thiols to the resulting unsaturated amino acids to form
      lanthionine and methyllanthionine bridges, respectively. Importantly, the
      structural and functional diversity of the lantibiotics is much broader than
      previously imagined. Here we discuss this growing collection of molecules and
      introduce some recently discovered peptides, review advances in enzymology and
      protein engineering, and discuss the regulatory networks that govern the
      synthesis of the lantibiotics by the producing organisms.

PMID- 17506683
TI  - Endolithic microbial ecosystems.
AB  - The endolithic environment, the pore space in rocks, is a ubiquitous microbial
      habitat and an interface between biology and geology. Photosynthesis-based
      endolithic communities inhabit the outer centimeters of rocks exposed to the
      surface, and offer model systems for microbial ecology, geobiology, and
      astrobiology. Endolithic ecosystems are among the simplest microbial ecosystems
      known and as such provide tractable models for testing ecological hypotheses.
      Such hypotheses have been difficult to test because microbial ecosystems are
      extraordinarily diverse. We review here recent culture-independent, ribosomal RNA
      based studies that evaluate hypotheses about endolithic ecosystems, and provide
      insight for understanding general principles in microbial ecology. Comparison of
      endolithic communities supports the principle that patterns of microbial
      diversity are governed by similar principles observed in macroecological systems.
      Recent results also explore geobiological processes that shape the current
      biosphere and potentially provide clues to life's history on Earth and where to
      seek life elsewhere in the Solar System.

PMID- 17506684
TI  - Biogenesis of the gram-negative bacterial outer membrane.
AB  - The cell envelope of gram-negative bacteria consists of two membranes, the inner
      and the outer membrane, that are separated by the periplasm. The outer membrane
      consists of phospholipids, lipopolysaccharides, integral membrane proteins, and
      lipoproteins. These components are synthesized in the cytoplasm or at the inner
      leaflet of the inner membrane and have to be transported across the inner
      membrane and through the periplasm to assemble eventually in the correct
      membrane. Recent studies in Neisseria meningitidis and Escherichia coli have led
      to the identification of several machineries implicated in these transport and
      assembly processes.

PMID- 17506685
TI  - Chlorophyll biosynthesis in bacteria: the origins of structural and functional
      diversity.
AB  - The use of photochemical reaction centers to convert light energy into chemical
      energy, chlorophototrophy, occurs in organisms belonging to only five eubacterial
      phyla: Cyanobacteria, Proteobacteria, Chlorobi, Chloroflexi, and Firmicutes. All
      chlorophototrophs synthesize two types of pigments: (a) chlorophylls and
      bacteriochlorophylls, which function in both light harvesting and uniquely in
      photochemistry; and (b) carotenoids, which function primarily as photoprotective
      pigments but can also participate in light harvesting. Although hundreds of
      carotenoids have been identified, only 12 types of chlorophylls (Chl a, b, d;
      divinyl-Chl a and b; and 8(1)-hydroxy-Chl a) and bacteriochlorophylls (BChl a, b,
      c, d, e, and g) are currently known to occur in bacteria. This review summarizes
      recent progress in the identification of genes and enzymes in the biosynthetic
      pathways leading to Chls and BChls, the essential tetrapyrrole cofactors of
      photosynthesis, and addresses the mechanisms for generating functional diversity
      for solar energy capture and conversion in chlorophototrophs.

PMID- 17506687
TI  - As the worm turns: the earthworm gut as a transient habitat for soil microbial
      biomes.
AB  - The gut of the earthworm constitutes a mobile anoxic microzone to which the
      microorganisms of aerated soils are subjected. During gut passage, the in situ
      factors of the earthworm gut, which include anoxia and high concentrations of
      organic substrates, appear to greatly stimulate a subset of ingested soil
      microorganisms, including denitrifying and fermentative bacteria. The selective
      stimulation of ingested soil microbes by the unique microconditions of the
      earthworm gut (a) results in the in vivo emission of denitrification-derived
      dinitrogen (N(2)) and the greenhouse gas nitrous oxide (N(2)O) by the earthworm,
      and (b) might affect the fitness, culturability, and diversity of certain members
      of soil microbial biomes. These observations illustrate the impact that soil
      macrofauna might have on terrestrial nitrogen cycle processes via their transient
      hosting of ingested prokaryotes.

PMID- 17506688
TI  - Morphology, molecular codes, and circuitry produce the three-dimensional
      complexity of the cerebellum.
AB  - The most noticeable morphological feature of the cerebellum is its folded
      appearance, whereby fissures separate its anterior-posterior extent into lobules.
      Each lobule is molecularly coded along the medial-lateral axis by parasagittal
      stripes of gene expression in one cell type, the Purkinje cells (PCs).
      Additionally, within each lobule distinct combinations of afferents terminate and
      supply the cerebellum with synchronized sensory and motor information.
      Strikingly, afferent terminal fields are organized into parasagittal domains, and
      this pattern bears a close relationship to PC molecular coding. Thus, cerebellum
      three-dimensional complexity obeys a basic coordinate system that can be broken
      down into morphology and molecular coding. In this review, we summarize the
      sequential stages of cerebellum development that produce its laminar structure,
      foliation, and molecular organization. We also introduce genes that regulate
      morphology and molecular coding, and discuss the establishment of topographical
      circuits within the context of the two coordinate systems. Finally, we discuss
      how abnormal cerebellar organization may result in neurological disorders like
      autism.

PMID- 17506689
TI  - The role of Pax genes in the development of tissues and organs: Pax3 and Pax7
      regulate muscle progenitor cell functions.
AB  - Pax genes play key roles in the formation of tissues and organs during
      embryogenesis. Pax3 and Pax7 mark myogenic progenitor cells and regulate their
      behavior and their entry into the program of skeletal muscle differentiation.
      Recent results have underlined the importance of the Pax3/7 population of cells
      for skeletal muscle development and regeneration. We present our current
      understanding of different aspects of Pax3/7 function in myogenesis, focusing on
      the mouse model. This is compared with that of other Pax proteins in the
      emergence of tissue specific lineages and their differentiation as well as in
      cell survival, proliferation, and migration. Finally, we consider the molecular
      mechanisms that underlie the function of Pax transcription factors, including the
      cofactors and regulatory networks with which they interact.

PMID- 17506690
TI  - Hyaluronan in tissue injury and repair.
AB  - A hallmark of tissue injury and repair is the turnover of extracellular matrix
      components. This review focuses on the role of the glycosaminoglycan hyaluronan
      in tissue injury and repair. Both the synthesis and degradation of extracellular
      matrix are critical contributors to tissue repair and remodeling. Fragmented
      hyaluronan accumulates during tissue injury and functions in ways distinct from
      the native polymer. There is accumulating evidence that hyaluronan degradation
      products can stimulate the expression of inflammatory genes by a variety of
      immune cells at the injury site. CD44 is the major cell-surface hyaluronan
      receptor and is required to clear hyaluronan degradation products produced during
      lung injury; impaired clearance of hyaluronan results in persistent inflammation.
      However, hyaluronan fragment stimulation of inflammatory gene expression is not
      dependent on CD44 in inflammatory macrophages. Instead, hyaluronan fragments
      utilize both Toll-like receptor (TLR) 4 and TLR2 to stimulate inflammatory genes
      in macrophages. Hyaluronan also is present on the cell surface of lung alveolar
      epithelial cells and provides protection against tissue damage by interacting
      with TLR2 and TLR4 on these parenchymal cells. The simple repeating structure of
      hyaluronan appears to be involved in a number of important aspects of
      noninfectious tissue injury and repair that are dependent on the size and
      location of the polymer as well as the interacting cells. Thus, the interactions
      between the endogenous matrix component hyaluronan and its signaling receptors
      initiate inflammatory responses, maintain structural cell integrity, and promote
      recovery from tissue injury.

PMID- 17506693
TI  - The thymus as an inductive site for T lymphopoiesis.
AB  - Like all hematopoietic cells, T lymphocytes are derived from bone-marrow-resident
      stem cells. However, whereas most blood lineages are generated within the marrow,
      the majority of T cell development occurs in a specialized organ, the thymus.
      This distinction underscores the unique capacity of the thymic microenvironment
      to support T lineage restriction and differentiation. Although the identity of
      many of the contributing thymus-derived signals is well established and rooted in
      highly conserved pathways involving Notch, morphogenetic, and protein tyrosine
      kinase signals, the manner in which the ensuing cascades are integrated to
      orchestrate the underlying processes of T cell development remains under
      investigation. This review focuses on the current definition of the early stages
      of T cell lymphopoiesis, with an emphasis on the nature of thymus-derived signals
      delivered to T cell progenitors that support the commitment and differentiation
      of T cells toward the alphabeta and gammadelta T cell lineages.

PMID- 17506691
TI  - Cilia and developmental signaling.
AB  - Recent studies have revealed unexpected connections between the mammalian
      Hedgehog (Hh) signal transduction pathway and the primary cilium, a microtubule
      based organelle that protrudes from the surface of most vertebrate cells.
      Intraflagellar transport proteins, which are required for the construction of
      cilia, are essential for all responses to mammalian Hh proteins, and proteins
      required for Hh signal transduction are enriched in primary cilia. The phenotypes
      of different mouse mutants that affect ciliary proteins suggest that cilia may
      act as processive machines that organize sequential steps in the Hh signal
      transduction pathway. Cilia on vertebrate cells are likely to be important in
      additional developmental signaling pathways and are required for PDGF receptor
      alpha signaling in cultured fibroblasts. Cilia are not essential for either
      canonical or noncanonical Wnt signaling, although cell-type-specific modulation
      of cilia components may link cilia and Wnt signaling in some tissues. Because
      ciliogenesis in invertebrates is limited to a very small number of specialized
      cell types, the role of cilia in developmental signaling pathways is likely a
      uniquely vertebrate phenomenon.

PMID- 17506694
TI  - SNARE-ware: the role of SNARE-domain proteins in plant biology.
AB  - In yeast and animal cells, members of the superfamily of N-ethylmaleimide
      sensitive factor adaptor protein receptor (SNARE)-domain-containing proteins are
      key players in vesicle-associated membrane fusion events during transport
      processes between individual compartments of the endomembrane system, including
      exocytosis and endocytosis. Compared with genomes of other eukaryotes, genomes of
      monocotyledonous and dicotyledonous plants encode a surprisingly high number of
      SNARE proteins, suggesting vital roles for this protein class in higher plant
      species. Although to date it remains elusive whether plant SNARE proteins
      function like their yeast and animal counterparts, genetic screens have recently
      begun to unravel the variety of biological tasks in which plant SNAREs are
      involved. These duties involve fundamental processes such as cytokinesis, shoot
      gravitropism, pathogen defense, symbiosis, and abiotic stress responses,
      suggesting that SNAREs contribute essentially to many facets of plant biology.

PMID- 17506695
TI  - microRNA functions.
AB  - microRNAs (miRNAs) are small noncoding RNAs that play important roles in
      posttranscriptional gene regulation. In animal cells, miRNAs regulate their
      targets by translational inhibition and mRNA destabilization. Here, we review
      recent work in animal models that provide insight into the diverse roles of
      miRNAs in vivo.

PMID- 17506696
TI  - Following the chromosome path to the garden of the genome.
AB  - I have been fascinated by chromosomes for longer than I care to mention; their
      beautiful structure, cell-type-specific changes in morphology, and elegant
      movements delight me. Shortly before I began graduate study, the development of
      nucleic acid hybridization made it possible to compare two nucleic acids whether
      or not their sequences were known. From this stemmed a progression of development
      in tools and techniques that continues to enhance our understanding of how
      chromosomes function. As my PhD project I contributed to this progression by
      developing in situ hybridization, a technique for hybridization to nucleic acids
      within their cellular context. Early studies with this technique initiated
      several lines of research, two of which I describe here, that I have pursued to
      this day. First, analysis of RNA populations by hybridization to polytene
      chromosomes (a proto-microarray-type experiment) led us to characterize levels of
      regulation during heat shock beyond those recognizable by puffing studies. We
      found also that one still-undeciphered major heat shock puff encodes a novel set
      of RNAs for which we propose a regulatory role. Second, localization of various
      multicopy DNA sequences has suggested roles for them in chromosome structure:
      Most recently we have found that Drosophila telomeres consist of and are
      maintained by special non-LTR (long terminal repeat) retrotransposons.

PMID- 17506698
TI  - Controls of germline stem cells, entry into meiosis, and the sperm/oocyte
      decision in Caenorhabditis elegans.
AB  - The Caenorhabditis elegans germ line provides an exceptional model for analysis
      of the molecular controls governing stem cell maintenance, the cell cycle
      transition from mitosis to meiosis, and the choice of sexual identity-sperm or
      oocyte. Germline stem cells are maintained in an undifferentiated state within a
      well-defined niche formed by a single somatic cell, the distal tip cell (DTC). In
      both sexes, the DTC employs GLP-1/Notch signaling and FBF/PUF RNA-binding
      proteins to maintain stem cells and promote mitotic divisions, three additional
      RNA regulators (GLD-1/quaking, GLD-2/poly(A) polymerase, and GLD-3/Bicaudal-C)
      control entry into meiosis, and FOG-1/CPEB and FOG-3/Tob proteins govern sperm
      specification. These key regulators are part of a robust regulatory network that
      controls germ cell proliferation, stem cell maintenance, and sex determination.
      Parallels with controls in other organisms include the use of PUF proteins for
      stem cell maintenance and the prominence of mRNA regulation for the control of
      germline development.

PMID- 17506697
TI  - Biogenesis and function of multivesicular bodies.
AB  - The two major cellular sites for membrane protein degradation are the proteasome
      and the lysosome. Ubiquitin attachment is a sorting signal for both degradation
      routes. For lysosomal degradation, ubiquitination triggers the sorting of cargo
      proteins into the lumen of late endosomal multivesicular bodies (MVBs)/endosomes.
      MVB formation occurs when a portion of the limiting membrane of an endosome
      invaginates and buds into its own lumen. Intralumenal vesicles are degraded when
      MVBs fuse to lysosomes. The proper delivery of proteins to the MVB interior
      relies on specific ubiquitination of cargo, recognition and sorting of
      ubiquitinated cargo to endosomal subdomains, and the formation and scission of
      cargo-filled intralumenal vesicles. Over the past five years, a number of
      proteins that may directly participate in these aspects of MVB function and
      biogenesis have been identified. However, major questions remain as to exactly
      what these proteins do at the molecular level and how they may accomplish these
      tasks.

PMID- 17506699
TI  - The cell biology of synaptic plasticity: AMPA receptor trafficking.
AB  - The cellular processes that govern neuronal function are highly complex, with
      many basic cell biological pathways uniquely adapted to perform the elaborate
      information processing achieved by the brain. This is particularly evident in the
      trafficking and regulation of membrane proteins to and from synapses, which can
      be a long distance away from the cell body and number in the thousands. The
      regulation of neurotransmitter receptors, such as the AMPA-type glutamate
      receptors (AMPARs), the major excitatory neurotransmitter receptors in the brain,
      is a crucial mechanism for the modulation of synaptic transmission. The levels of
      AMPARs at synapses are very dynamic, and it is these plastic changes in synaptic
      function that are thought to underlie information storage in the brain. Thus,
      understanding the cellular machinery that controls AMPAR trafficking will be
      critical for understanding the cellular basis of behavior as well as many
      neurological diseases. Here we describe the life cycle of AMPARs, from their
      biogenesis, through their journey to the synapse, and ultimately through their
      demise, and discuss how the modulation of this process is essential for brain
      function.

PMID- 17506700
TI  - Wing vein patterning in Drosophila and the analysis of intercellular signaling.
AB  - The positioning and elaboration of ectodermal veins in the wing of Drosophila
      melanogaster rely on widely utilized developmental signals, including those
      mediated by EGF, BMP, Hedgehog, Notch, and Wnt. Analysis of vein patterning
      mutants, using the molecular and genetic mosaic techniques available in
      Drosophila, has provided important insights into how a combination of short-range
      and long-range signaling can pattern a simple epidermal tissue. Moreover,
      venation has become a powerful system for isolating and analyzing novel
      components in these signaling pathways. I here review the basic events of vein
      patterning and give examples of how changes in venation have been used to
      identify important features of cell signaling pathways.

PMID- 17506701
TI  - Secretory mechanisms in cell-mediated cytotoxicity.
AB  - Cytotoxic T lymphocytes (CTLs) play a critical role in the immune system; they
      are able to recognize and destroy virally infected and tumorigenic cells.
      Specific recognition of MHC class I-peptide complexes by the T cell receptor
      (TcR) results in precise delivery of lytic granules to the target cell, sparing
      neighboring cells and the CTL itself. Over the past 10 years various studies have
      eludicated the mechanisms that lead to the rapid polarization of the secretory
      apparatus in CTLs. These studies highlight similarities and differences between
      polarity and secretory mechanisms seen in other cell types and developmental
      systems. This review focuses on recent advances in our understanding of the
      molecular basis of polarized secretion from CTLs and the novel mechanism used by
      these cells to deliver their lethal hit.

PMID- 17506702
TI  - Maintaining peroxisome populations: a story of division and inheritance.
AB  - Eukaryotic cells divide their metabolic labor between functionally distinct,
      membrane-enveloped organelles, each precisely tailored for a specific set of
      biochemical reactions. Peroxisomes are ubiquitous, endoplasmic reticulum-derived
      organelles that perform requisite biochemical functions intimately connected to
      lipid metabolism. Upon cell division, cells have to strictly control peroxisome
      division and inheritance to maintain an appropriate number of peroxisomes in each
      cell. Peroxisome division follows a specific sequence of events that include
      peroxisome elongation, membrane constriction, and peroxisome fission. Pex11
      proteins mediate the elongation step of peroxisome division, whereas dynamin
      related proteins execute the final fission. The mechanisms responsible for
      peroxisome membrane constriction are poorly understood. Molecular players
      involved in peroxisome inheritance are just beginning to be elucidated. Inp1p and
      Inp2p are two recently identified peroxisomal proteins that perform antagonistic
      functions in regulating peroxisome inheritance in budding yeast. Inp1p promotes
      the retention of peroxisomes in mother cells and buds by attaching peroxisomes to
      as-yet-unidentified cortical structures. Inp2p is implicated in the motility of
      peroxisomes by linking them to the Myo2p motor, which then propels their movement
      along actin cables. The functions of Inp1p and Inp2p are cell cycle regulated and
      coordinated to ensure a fair distribution of peroxisomes at cytokinesis.

PMID- 17506703
TI  - The small G proteins of the Arf family and their regulators.
AB  - Small G proteins play a central role in the organization of the secretory and
      endocytic pathways. The majority of such small G proteins are members of the Rab
      family, which are anchored to the bilayer by C-terminal prenyl groups. However,
      the recruitment of some effectors, including vesicle coat proteins, is mediated
      by a second class of small G proteins that is unique in having an N-terminal
      amphipathic helix that becomes available for membrane insertion upon GTP binding.
      Sar1, Arf1, and Arf6 are the best-characterized members of this ADP-ribosylation
      factor (Arf) family. In addition, all eukaryotes contain additional distantly
      related G proteins, often called Arf like, or Arls. The complete Arf family in
      humans has 29 members. The roles of these related G proteins are poorly
      understood, but recent work has shown that some are involved in membrane traffic
      or organizing the cytoskeleton. Here we review what is known about all the
      members of the Arf family, along with the known regulatory molecules that convert
      them between GDP- and GTP-bound states.

PMID- 17506705
TI  - Improving the food provided and food safety practices in out-of-school-hours
      services.
AB  - ISSUE ADDRESSED: Food provided and food safety and serving practices in out-of
      school-hours (OOSH) services. METHODS: Health promotion strategies, developed in
      partnership with an advisory committee, were directed at three main areas:
      supporting local services; developing statewide training and resources; and
      advocacy. RESULTS: Significant improvements were seen in the food provided, food
      safety and serving practices and the number of services with planned menus and
      nutrition and food safety policies. CONCLUSIONS: This project is one of the first
      implemented and evaluated in the OOSH setting. Statistically significant
      improvements were achieved in the food provided, food safety and serving
      practices, and menu and policy development. The project also increased the
      capacity of the OOSH sector to improve children's health by making suitable
      nutrition and food safety resources and training available to OOSH services
      across New South Wales.

PMID- 17506706
TI  - The relative transcription index: a gene expression based metric for
      prioritization of drug candidates.
AB  - Efficient compound selection remains a key challenge in drug discovery today. The
      goal is to identify developable drug candidates early in the screening process
      while simultaneously flagging compounds with off-target effects indicative of
      liabilities or alternate indications. This goal overlaps but is distinct from the
      goal of toxicogenomics which is focused primarily on identifying toxicity
      signatures of lead candidates in key tissues. We propose a framework where global
      changes in gene expression levels in response to compounds can be used as an
      objective metric for early compound prioritization. We call this metric the
      Relative Transcription Index (RTI). RTI is a measure of the relative activity of
      compounds as ascertained by their effects on transcription at a genome-wide
      level. Compounds with a low RTI affect the expression of only a few genes whereas
      compounds with a high RTI affect the expression of a large number of genes. This
      information is useful for differentiating compounds that, based on phenotypic
      assays alone, may appear to be equally efficacious. Since compounds with high RTI
      are more likely to display off-target effects, the RTI metric, if implemented
      early in the screening process, can become a valuable tool for compound
      selection. The utility of the RTI metric is demonstrated by its application to
      two different gene expression datasets--one involving modulators of the liver X
      receptor (LXR) and the other concerning antibacterial compounds belonging to
      diverse mechanistic classes.

PMID- 17506707
TI  - Oligonucleotide profiling for discriminating bacteria in bacterial communities.
AB  - Based on the relative ratios of di- and tri-nucleotides in the DNA sequences, the
      profiles of 164 genome sequences from 152 representative microbial organisms were
      computed. By comparing the profiles of the genomes and their substrings with
      length 500 bps, the fluctuations of the relative abundances of di- and tri
      nucleotides of these genomic sequences were analyzed. A new method to
      discriminate the origins of orphan DNA sequences was proposed, and the origins of
      17 uncultured bacterium sequences from a bacterial community in the human gut
      were postulated and discussed.

PMID- 17506708
TI  - Traceless synthesis of 3-N-substituted-2-thioxoquinazoline-4-ones on a soluble
      polymeric support.
AB  - The synthesis of 3-N-substituted-2-thioxoquinazoline-4-ones is described with a
      traceless linker strategy using poly(ethylene glycol) (PEG) as a soluble
      polymeric support. Staudinger-Aza-Wittig reaction of PEG-supported azide with
      Ph(3)P and CS(2) gave the corresponding PEG-supported phenyl isothiocyanate.
      Treatment of the phenyl isothiocyanate with different primary amines led, via
      intramolecular cyclization and simultaneous cleavage from PEG, to 2
      thioxoquinazoline-4-ones with of moderate to excellent yields.

PMID- 17506709
TI  - Development of self-indicating resin.
AB  - Previously, we have reported the development and application of self-indicating
      resins (SIR), materials which can indicate presence or absence of amines in the
      reaction solution by the conspicuous color change of a phenolsulfophthalein type
      dye immobilized on resin beads [2a]. Although the functionality necessary for
      attaching the dye to the resins could be readily introduced by the Suzuki-Miyaura
      coupling during the synthesis of the SIR 1, this approach was only applicable to
      the dyes containing suitable functionality for the cross-coupling reaction. In
      this article we describe a new approach of immobilizing the indicating dyes onto
      the resin support. The dyes suitable for loading onto aminomethyl polystyrene
      (PS) resin were prepared by Friedel-Crafts reaction of 2-sulfoterephthalic
      anhydride with a wide range of phenols. Using this new route, the SIR 6c was
      readily prepared in >100g quantities. Use of the SIR 6c in the synthesis of a 144
      member urea library was demonstrated and the SIR successfully indicated the
      endpoint of the reaction between amines and isocyanates.

PMID- 17506710
TI  - Oligonucleotide fingerprinting of arrayed genomic DNA sequences using LNA
      modified hybridization probes.
AB  - Recently, we established a robust method for the detection of hybridization
      events using a DNA microarray deposited on a nanoporous membrane. Here, in a
      follow-up study, we demonstrate the performance of this approach on a larger set
      of LNA-modified oligoprobes and genomic DNA sequences. Twenty-six different LNA
      modified 7-mer oligoprobes were hybridized to a set of 66 randomly selected human
      genomic DNA clones spotted on a nanoporous membrane slide. Subsequently, assay
      sensitivity analysis was performed using receiver operating characteristic (ROC)
      curves. Comparison of LNA-modified heptamers and DNA heptamers revealed that the
      LNA modification clearly improved sensitivity and specificity of hybridization
      experiment. Clustering analysis was applied in order to test practical
      performance of hybridization experiments with LNA-modified oligoprobes in
      recognizing similarity of genomic DNA sequences. Comparing the results with the
      theoretical sequence clusters, we conclude that the application of LNA-modified
      oligoprobes allows for reliable clustering of DNA sequences which reflects the
      underlying sequence homology. Our results show that LNA-modified oligoprobes can
      be used effectively to unravel sequence similarity of DNA sequences and thus, to
      characterize the content of unknown DNA libraries.

PMID- 17506711
TI  - A naturally logical representation for DNA primary sequences.
AB  - In this paper, we (1) introduce a logical representation (LR) for DNA primary
      sequences; (2) show relations between LR and some other representations including
      the characteristic sequences of a DNA sequence, Randic's 2-D, 4-D
      representations, and Z-curve (a 3-D graphical representation); and (3) outline
      the constructions of the S/S matrix specific for a logical sequence and its 2*2
      condensed matrix.

PMID- 17506712
TI  - Compound Hub: efficiency gains through innovative sample management processes.
AB  - While significant investments are made across the industry and increasingly also
      in academia to enhance or build a compound file, the efficient sourcing of
      compounds from in-house medical chemistry is frequently seen as a challenge. This
      article introduces the Compound Hub strategy developed at the Novartis Compound
      Archive. Central Compound Hubs in Basel and Cambridge were combined with web
      based ordering of compounds and assays, providing assay-ready, solubilized
      samples to labs anywhere in the global research organization. Relieving
      scientists from time-intensive sample preparation tasks, error rates could be
      reduced through electronic processing and tracking of compounds/assays and the
      capture of medicinal chemistry compounds for the compound library could be
      increased by 75%.

PMID- 17506713
TI  - Fluorescence-based adenylyl cyclase assay adaptable to high throughput screening.
AB  - The second messenger cAMP has been implicated in numerous cellular processes such
      as glycogen metabolism, muscle contraction, learning and memory, and
      differentiation and development. Genetic evidence suggests that the enzyme that
      produces cAMP, adenylyl cyclase (AC), may be involved in pathogenesis in many of
      these cellular processes. In addition, these data suggest that membrane-bound ACs
      may be valuable targets for therapeutics to treat pathogenesis of these
      processes. The development of a robust real-time adenylyl cyclase assay that can
      be scalable to high-throughput screening could help in the development of novel
      therapeutics. Here we report a novel fluorescence-based cyclase assay using
      Bodipy FL GTPgammaS (BGTPgammaS). The fluorescence of the Bodipy moiety of
      BGTPgammaS was dramatically enhanced by incubation with the minimal catalytic
      core of wild-type-AC (wt-AC) and a mutant with decreased purine selectivity (mut
      AC), in an AC activation-dependent manner. No increase in fluorescence was
      observed using Bodipy FL ATPgammaS (BATPgammaS) as substrate for either wt-AC or
      mut-AC. Using BGTPgammaS, forskolin, Gsalpha.GTPgammaS and the divalent cation
      Mn(2+) potently enhanced the rate of fluorescence increase in a concentration
      dependent manner. The fluorescence enhancement of the Bodipy moiety was inhibited
      by known inhibitors of AC such as 2'deoxy,3'AMP and 2',5'-dideoxy-3'ATP.
      Furthermore, the fluorescence assay is adaptable to 96-well and 384-well
      multiplate format and is thus applicable to high throughput screening
      methodologies.

PMID- 17506715
TI  - Treatment of experimental myocarditis via modulation of the renin-angiotensin
      system.
AB  - The renin-angiotensin system is primarily responsible for regulating vascular
      tone. Drugs that inhibit this pathway, angiotensin-converting enzyme inhibitors
      and angiotensin receptor antagonists, are widely used to treat hypertension and a
      variety of cardiomyopathies. Recent studies have shown that, in addition to
      reducing blood pressure, these drugs also modulate inflammation, adhesion
      molecule expression, and fibrosis. To assess the therapeutic potential of these
      inhibitory agents for the treatment of inflammatory heart disease, the drugs have
      been tested in experimental models of infectious and autoimmune myocarditis. This
      review summarizes the results of studies examining the efficacy of angiotensin
      converting enzyme inhibitors and angiotensin receptor antagonists for the
      treatment of mouse models of virus-induced and parasite-induced myocarditis, as
      well as autoimmune cardiomyopathy. The collective results strongly support the
      use of renin-angiotensin modulation for the treatment of myocarditis.
      Importantly, this therapeutic approach seems to downregulate autoimmunity without
      causing immune suppression which may enhance the survival of the disease
      initiating infectious agent.

PMID- 17506716
TI  - Effect of an angiotensin II receptor blocker and two angiotensin converting
      enzyme inhibitors on transforming growth factor-beta (TGF-beta) and alpha
      actomyosin (alpha SMA), important mediators of radiation-induced pneumopathy and
      lung fibrosis.
AB  - Progressive, irreversible fibrosis is one of the most clinically significant
      consequences of ionizing radiation on normal tissue. When applied to lungs, it
      leads to a complication described as idiopathic pneumonia syndrome (IPS) and
      eventually to organ fibrosis. For its high mortality, the condition precludes
      treatment with high doses of radiation. There is widespread interest to
      understand the pathogenetic mechanisms of IPS and to find drugs effective in the
      prevention of its development. This report summarizes our experience with the
      protective effects of L 158,809, an angiotensin II (ANG II) receptor blocker, and
      two angiotensin converting enzyme (ACE) inhibitors in the development of IPS and
      the role of transforming growth factor beta (TGF-beta) and of alpha-actomyosin
      (alpha SMA) in pathogenesis of radiation induced pulmonary fibrosis in an
      experimental model of bone marrow transplant (BMT). Male WAG/Riji/MCV rats
      received total body irradiation and a regimen of cyclophosphamide (CTX) in
      preparation for bone marrow transplant. While one group of animals remained
      untreated, the remainders were subdivided into three groups, each of them
      receiving either the ANG II receptor blocker or one of the two ACE inhibitors
      (Captopril or Enalapril). Each of the three drugs was administered orally from 11
      days before the transplant up to 56 days post transplant. At sacrifice time the
      irradiated rats receiving only CTX showed a chronic pneumonitis with septal
      fibrosis and vasculitis affecting, in particular, small caliber pulmonary
      arteries and arterioles. Their lung content of hydroxyproline was also markedly
      elevated in association with the lung concentrations of thromboxane (TXA2) and
      prostaglandin (PGI(2)), (two markers of pulmonary endothelial damage). A
      significant increase of alpha actomyosin staining was observed in vessels, septa
      and macrophages of the same animals which also overexpressed TGF-beta. When L
      158,809, Captopril and Enalapril were added to the radiation and cytoxan
      treatment, a significant amelioration of the histological damage as well as the
      overexpression of alpha SMA was observed. Lung concentrations of hydroxyproline,
      PGI(2), TXA2 and TGF-beta were also observed in these animals so that the values
      of these compounds were closer to those measured in untreated control rats than
      to their irradiated and cytoxan treated counterparts. Angiotensin II plays an
      important role in the regulation of TGF-beta and alpha SMA, two proteins involved
      in the pathogenesis of pulmonary fibrosis. The finding that ACE inhibitors or ANG
      II receptor blockers protect the lungs from radiation induced pneumonitis and
      fibrosis reaffirms the role that ANG II plays in this inflammatory process and
      suggests an additional indication of treatment of this condition, thus opening a
      new potential pharmacologic use of these drugs.

PMID- 17506717
TI  - Treatment of radiation nephropathy with ACE inhibitors and AII type-1 and type-2
      receptor antagonists.
AB  - Radiation nephropathy has emerged as a significant complication of bone marrow
      transplantation and radionuclide radiotherapy, and is a potential sequela of
      radiological terrorism and radiation accidents. In the early 1990's, it was
      demonstrated that experimental radiation nephropathy could be treated with a
      thiol-containing ACE inhibitor, captopril. Further studies have shown that
      enalapril (a non-thiol ACE inhibitor) is also effective in the treatment of
      experimental radiation nephropathy, as are both AII type-1 (AT(1)) and type-2
      (AT(2)) receptor antagonists. ACE inhibitors and AII receptor antagonists are
      also effective in the mitigation (prevention) of radiation nephropathy. Other
      types of antihypertensive drugs are ineffective in mitigation, but brief use of a
      high-salt diet in the immediate post-irradiation period significantly decreases
      renal injury. There are differences between mitigation and treatment of radiation
      nephropathy that imply that different mechanisms are operating. First, a high
      salt diet is effective in the mitigation of radiation nephropathy, but
      deleterious on the treatment of established disease. Second, AT(1) blockade is
      more effective than ACE inhibition for mitigation of radiation nephropathy, but
      equally effective for treatment. Third, the efficacy of AT(1) blockade and ACE
      inhibition is highly dependent on drug dose in mitigation of radiation
      nephropathy, but not so in treatment. Finally, while AT(2) blockade augments the
      benefit of AT(1) blockade in mitigation of radiation nephropathy, it does not do
      so in treatment. We hypothesize that while mitigation of radiation nephropathy
      works by suppression of the renin-angiotensin system, treatment of established
      radiation nephropathy requires blood pressure control in addition to (or possibly
      instead of) suppression of the renin-angiotensin system.

PMID- 17506718
TI  - Effects on cytokines and histology by treatment with the ACE inhibitor captopril
      and the antioxidant retinoic acid in the monocrotaline model of experimentally
      induced lung fibrosis.
AB  - Monocrotaline (MCT), a pyrrolizidine alkaloid extracted from the shrub Crotalaria
      spectabilis, induces in the lungs of many mammalian species severe hypertension
      and fibrosis. Previous work with MCT-induced lung disease in rats has shown that
      some of the steps to progressive fibrosis can be interrupted or decreased by
      intervention with retinoic acid (RA) or with the angiotensin converting enzyme
      inhibitor, captopril. This report emphasizes the pathology and cytokines present
      in lungs of rats in the MCT model of hypertension and fibrosis in 8 treatment
      groups, six per group: (1) controls, not treated; (2) captopril; (3) RA; (4)
      combined captopril and RA. Groups 5-8 replicated groups 1-4 and also received MCT
      subcutaneously. Tissues were harvested at 28 days for histopathology and
      measurement of cytokines TGFbeta, TNFalpha, interleukin 6, and IFN_. TGFbeta was
      depressed at 28 days by MCT, an effect reversed by a combination of captopril and
      RA. RA influences production of an important Th1 cytokine, IFN_, and demonstrated
      the greatest limitation of MCT-induced TNFalpha. The MCT-induced lung pathology
      of vasculitis, interstitial pneumonia and fibrosis was limited by captopril.
      Smooth muscle actin was overexpressed in MCT treated animals receiving RA, an
      effect reduced with captopril. Overall, the study confirmed the existence of a
      protective effect for both captopril and RA from MCT-induced lung damage at 30
      days. No synergistic or antagonistic activity was observed when the two drugs
      were administered together. Each of the drugs exerts different and particular
      effects on serum and tissue levels of various cytokines, suggesting that each
      drug is efficient at different points of attack in the control of lung fibrosis.

PMID- 17506719
TI  - Role of renin angiotensin system inhibitors in cardiovascular and renal
      protection: a lesson from clinical trials.
AB  - Beneficial effects of angiotensin converting enzyme inhibitors (ACEI) and
      angiotensin type 1 receptor (AT1) blockers in patients with cardiovascular and
      renal diseases have been clearly demonstrated in numerous large outcomes studies.
      In patients with heart failure (HF), ACEI have been shown to reduce overall
      mortality, mortality from cardiovascular causes, to increase life expectancy, as
      well as to preserve the renal function (CONSENSUS, SAVE, TRACE, AIRE, AIREX, CATS
      trials). In addition, in the PROGRESS study ACEI substantially decreased the risk
      of stroke and transient ischemic attacks in patients with cerebrovascular
      disorders. The HOPE and EUROPA studies confirmed that long term therapy with ACEI
      provides significant survival benefit in patients with broad range of
      atherosclerotic cardiovascular diseases. After these large and well designed
      clinical studies, ACEI have become standard therapy for routine secondary
      prevention in all patients with cardiovascular diseases, unless contraindicated.
      AT1 receptor blockers have been recently added to the cardiovascular therapeutic
      armamentarium. They are believed to provide additional protection by inhibition
      of locally synthesized angiotensin II on the level of AT1 receptor. The ELITE II,
      ValHeFT and CHARM studies have shown that AT1 receptor blockers are equally
      effective as ACEI in reduction of mortality and morbidity in patients with HF.
      Importantly, they may be used together with ACEI, or as alternative treatment in
      ACEI intolerant patients. Renal protection is another important effect of both
      ACEI and AT1 blockers that has been confirmed in several large clinical trials.
      The North American Microalbuminemia Study group and EUCLID group demonstrated
      significant reduction in progression of diabetic nephropathy in patients with
      insulin dependent diabetes mellitus (IDDM) treated with ACEI. AT1 receptor
      blockers are mainly studied in the non-insulin dependent diabetes mellitus
      (NIDDM) nephropathy. Four recent clinical trials (IRMA-2, DETAIL, RENAAL and
      IDNT) examined the effect of AT1 receptor blockers in patients with NIDDM
      nephropathy. These studies confirmed the beneficial effect of AT1 receptor
      blockers in patients with NIDDM nephropathy that was extended beyond the blood
      pressure reduction. Ongoing studies (ONTARGET, TRANSCEND and PROTECTION) should
      provide us with additional insights about cardiovascular, renal and other end
      organ protective effects of these therapeutics.

PMID- 17506720
TI  - Angiotensin-converting enzyme inhibitors in veterinary medicine.
AB  - Angiotensin-converting enzyme (ACE) inhibitors represent one of the most commonly
      used categories of drugs in canine and feline medicine. ACE inhibitors currently
      approved for use in veterinary medicine are benazepril, enalapril, imidapril and
      ramipril. They are all pro-drugs administered by oral route. A physiologically
      based model taking into account the saturable binding to ACE has been developed
      for pharmacokinetic analysis. The bioavailability of the active compounds from
      their respective pro-drug is low. The active metabolites are eliminated by renal,
      hepatorenal or biliary excretion, according to the drug. The elimination half
      life of the free fraction of the active compounds is very short (ranging from
      approximately 10 min to 2 h). ACE inhibitors are generally well tolerated.
      Benazepril, enalapril, imidapril and ramipril are approved for dogs with chronic
      heart failure (CHF). The efficacy of ACE inhibitors has been convincingly
      demonstrated in dogs with CHF, especially in those with chronic valvular disease.
      In such clinical settings, ACE inhibitors improve hemodynamics and clinical
      signs, and increase survival time. In cats with cardiovascular disease, little
      information is available except for reports of some benefit in cats with
      hypertrophic cardiomyopathy in two non-controlled investigations. ACE inhibitors
      have also a mild to moderate hypotensive effect. There is also evidence to
      recommend ACE inhibitors in dogs and cats with chronic renal failure (CRF). They
      decrease the glomerular capillary pressure, have antiproteinuric effects, tend to
      delay the progression of CRF and to limit the extent of renal lesions.

PMID- 17506721
TI  - Transplantation and other uses of human umbilical cord blood and stem cells.
AB  - Human umbilical cord blood (CB) has established itself as a legitimate source for
      hematopoeitic stem cell transplantations. Since the first transplantation was
      performed in 1988, it is estimated that approximately 4,000 patients, with
      malignant and non-malignant diseases, were transplanted with CB. Comparing to
      bone marrow transplants, cord blood's collection is easier and safer. It is also
      quicker to perform CB transplantation from the time of beginning of donor search.
      One of the major advantages of it is the naive nature of newborn's immune system.
      This allows transplantations with less restriction of the HLA system, and with
      fewer graft versus host disease (GVHD) cases. A true setback of CB
      transplantations is the slow pace of engraftment. This fact has negative impact
      on treatment related mortality and is related to the amount of stem cell infused.
      Since CB has limited nucleated cell dose, transplanting it to heavier patients,
      namely adults, poses many difficulties. But the skepticism about the possibility
      that CB might be used in adult hematopoetic stem cell transplantations, can
      decline after few large scale trials have shown that it is definitely a feasible
      procedure. Few fields of research might help to improve the outcome of CB
      transplantations. While some strategies are at different investigational stages,
      others are at advanced phases of clinical studies. Main strategies are based on
      expansion of the number of the stem cells in CB grafts, induction of a temporary
      engraftment with other stem cell sources, or reduction of the toxicity of the
      conditioning regimens. It is encouraging to witness that the outcome of CB
      transplantations is improving constantly. Other potential uses of CB are also
      discussed. It was used for gene transfer for primary immune deficiency, and it
      was also demonstrated in animal models that its stem cell could serve as
      regenerative cells in non-hematopoeitic injured tissues. CB has broad spectrum of
      possible uses, but hematopoeitic stem cell transplantation is still the major
      indication. In an era where 30-40% of patients will not have a matched related or
      unrelated donor, CB is a major alternative, which provide a true chance for cure
      for a wide variety of diseases.

PMID- 17506722
TI  - Retinoids as differentiating agents in oncology: a network of interactions with
      intracellular pathways as the basis for rational therapeutic combinations.
AB  - Retinoic acid and natural as well as synthetic derivatives (retinoids) are
      promising anti-neoplastic agents endowed with both therapeutic and
      chemopreventive potential. Although the treatment of acute promyelocic leukemia
      with all-trans retinoic acid is an outstanding example, the full potential of
      retinoids in oncology has not yet been exploited and a more generalized use of
      these compounds is not yet a reality. This may be the result of issues such as
      natural and induced resistance as well as local and systemic toxicity. One way to
      enhance the therapeutic and chemopreventive activity of retinoic acid and
      derivatives is to identify rational combinations between these compounds and
      other pharmacological agents. This is now possible given the wealth of
      information available on the biochemical and molecular mechanisms underlying the
      biological activity of retinoids. At the cellular level, the anti-leukemia and
      anti-cancer activity of retinoids is the result of three main actions, cell
      differentiation, growth inhibition and apoptosis. At the molecular level,
      retinoids act through the activation of nuclear-retinoic-acid-receptor-dependent
      and-independent pathways. The cellular pathways and molecular networks relevant
      for retinoid activity are modulated by a panoply of other intra-cellular and
      extra-cellular pathways that may be targeted by known drugs and other
      experimental therapeutics. The review article aims to summarize and critically
      discuss the available knowledge in the field and provide a rational framework
      that may be useful for the design of effective drug combinations with the
      potential to enhance the therapeutic index of retinoids.

PMID- 17506723
TI  - Novel role for insulin as an autocrine growth factor for malignant brain tumour
      cells.
AB  - AT/RTs (atypical teratoid/rhabdoid tumours) of the CNS (central nervous system)
      are childhood malignancies associated with poor survival rates due to resistance
      to conventional treatments such as chemotherapy. We characterized a panel of
      human AT/RT and MRT (malignant rhabdoid tumour) cell lines for expression of RTKs
      (receptor tyrosine kinases) and their involvement in tumour growth and survival.
      When compared with normal brain tissue, AT/RT cell lines overexpressed the IR
      (insulin receptor) and the IGFIR (insulin-like growth factor-I receptor).
      Moreover, insulin was secreted by AT/RT cells grown in serum-free medium. Insulin
      potently activated Akt (also called protein kinase B) in AT/RT cells, as compared
      with other growth factors, such as epidermal growth factor. Pharmacological
      inhibitors, neutralizing antibodies, or RNAi (RNA interference) targeting the IR
      impaired the growth of AT/RT cell lines and induced apoptosis. Inhibitors of the
      PI3K (phosphoinositide 3-kinase)/Akt pathway also impaired basal and insulin
      stimulated AT/RT cell proliferation. Experiments using RNAi and isoform-specific
      pharmacological inhibitors established a key role for the class I(A) PI3K
      p110alpha isoform in AT/RT cell growth and insulin signalling. Taken together,
      our results reveal a novel role for autocrine signalling by insulin and the IR in
      growth and survival of malignant human CNS tumour cells via the PI3K/Akt pathway.

PMID- 17506724
TI  - Novel xylan-binding properties of an engineered family 4 carbohydrate-binding
      module.
AB  - Molecular engineering of ligand-binding proteins is commonly used for
      identification of variants that display novel specificities. Using this approach
      to introduce novel specificities into CBMs (carbohydrate-binding modules) has not
      been extensively explored. Here, we report the engineering of a CBM, CBM4-2 from
      the Rhodothermus marinus xylanase Xyn10A, and the identification of the X-2
      variant. As compared with the wild-type protein, this engineered module displays
      higher specificity for the polysaccharide xylan, and a lower preference for
      binding xylo-oligomers rather than binding the natural decorated polysaccharide.
      The mode of binding of X-2 differs from other xylan-specific CBMs in that it only
      has one aromatic residue in the binding site that can make hydrophobic
      interactions with the sugar rings of the ligand. The evolution of CBM4-2 has thus
      generated a xylan-binding module with different binding properties to those
      displayed by CBMs available in Nature.

PMID- 17506728
TI  - Identification of quorum sensing-related regulons in Vibrio vulnificus by two
      dimensional gel electrophoresis and differentially displayed reverse
      transcriptase PCR.
AB  - Vibrio vulnificus is thought to employ a quorum-sensing system to control the
      expression of a global gene. In this study, proteomes and transcriptomes of a
      lacZ null mutant, VvSR Delta Z, and a luxS-smcR double mutant, VvSR Delta ZSR,
      were compared with the parent strain, VvAR, by means of two-dimensional gel
      electrophoresis (2D-PAGE) and differentially displayed reverse transcriptase PCR
      (DDRT-PCR). 2D-PAGE analysis showed that 36 protein spots were differentially
      expressed, 14 of which have been identified by peptide-mass fingerprinting. The
      expression of eight cellular proteins was repressed by luxS and smcR mutation: Zn
      dependent protease, 6-phosophofructokinase, periplasmic ABC-type Fe3(+) transport
      system, deoxyribose-phosphate aldolase, phosphomannomutase, orotidine-5'
      phosphate decarboxylase, uridylate kinase, and an unidentified protein. These
      proteins are involved in virulence, adaptation to environmental stress,
      biosynthesis of LPS, and cell multiplication. Phage shock protein A, a chemotaxis
      signal transduction protein, and an uncharacterized low-complexity protein were
      activated in the cellular components of the luxS-smcR mutant. However, only three
      proteins, of unknown function, were identified in the extracellular components of
      the mutants. Analysis of transcriptomes with DDRT-PCR showed that two genes,
      phosphoribosylformylglycinamidine synthase and ATP-dependent protease HslVU
      protease were regulated at the transcriptional level by luxS and smcR gene
      mutation. The results from this study show conclusively that luxS/smcR quorum
      sensing endows a global change in gene expression to V. vulnificus.

PMID- 17506725
TI  - CgNa, a type I toxin from the giant Caribbean sea anemone Condylactis gigantea
      shows structural similarities to both type I and II toxins, as well as
      distinctive structural and functional properties(1).
AB  - CgNa (Condylactis gigantea neurotoxin) is a 47-amino-acid- residue toxin from the
      giant Caribbean sea anemone Condylactis gigantea. The structure of CgNa, which
      was solved by 1H-NMR spectroscopy, is somewhat atypical and displays significant
      homology with both type I and II anemone toxins. CgNa also displays a
      considerable number of exceptions to the canonical structural elements that are
      thought to be essential for the activity of this group of toxins. Furthermore,
      unique residues in CgNa define a characteristic structure with strong negatively
      charged surface patches. These patches disrupt a surface-exposed cluster of
      hydrophobic residues present in all anemone-derived toxins described to date. A
      thorough characterization by patch-clamp analysis using rat DRG (dorsal root
      ganglion) neurons indicated that CgNa preferentially binds to TTX-S (tetrodotoxin
      sensitive) voltage-gated sodium channels in the resting state. This association
      increased the inactivation time constant and the rate of recovery from
      inactivation, inducing a significant shift in the steady state of inactivation
      curve to the left. The specific structural features of CgNa may explain its
      weaker inhibitory capacity when compared with the other type I and II anemone
      toxins.

PMID- 17506729
TI  - Recurrent wrong-route drug error - a professional shame.

PMID- 17506726
TI  - Naturally occurring and bioengineered apoA-I mutations that inhibit the
      conversion of discoidal to spherical HDL: the abnormal HDL phenotypes can be
      corrected by treatment with LCAT.
AB  - In the present study we have used adenovirus-mediated gene transfer of apoA-I
      (apolipoprotein A-I) mutants in apoA-I-/- mice to investigate how structural
      mutations in apoA-I affect the biogenesis and the plasma levels of HDL (high
      density lipoprotein). The natural mutants apoA-I(R151C)Paris, apoA-I(R160L)Oslo
      and the bioengineered mutant apoA-I(R149A) were secreted efficiently from cells
      in culture. Their capacity to activate LCAT (lecithin:cholesterol
      acyltransferase) in vitro was greatly reduced, and their ability to promote ABCA1
      (ATP-binding cassette transporter A1)-mediated cholesterol efflux was similar to
      that of WT (wild-type) apoA-I. Gene transfer of the three mutants in apoA-I-/-
      mice generated aberrant HDL phenotypes. The total plasma cholesterol of mice
      expressing the apoA-I(R160L)Oslo, apoA-I(R149A) and apoA-I(R151C)Paris mutants
      was reduced by 78, 59 and 61% and the apoA-I levels were reduced by 68, 64 and
      55% respectively, as compared with mice expressing the WT apoA-I. The CE
      (cholesteryl ester)/TC (total cholesterol) ratio of HDL was decreased and the
      apoA-I was distributed in the HDL3 region. apoA-I(R160L)Oslo and apoA-I(R149A)
      promoted the formation of prebeta1 and alpha4-HDL subpopulations and gave a
      mixture of discoidal and spherical particles. apoA-I(R151C)Paris generated
      subpopulations of different sizes that migrate between prebeta and alpha-HDL and
      formed mostly spherical and a few discoidal particles. Simultaneous treatment of
      mice with adenovirus expressing any of the three mutants and human LCAT
      normalized plasma apoA-I, HDL cholesterol levels and the CE/TC ratio. It also led
      to the formation of spherical HDL particles consisting mostly of alpha-HDL
      subpopulations of larger size. The correction of the aberrant HDL phenotypes by
      treatment with LCAT suggests a potential therapeutic intervention for HDL
      abnormalities that result from specific mutations in apoA-I.

PMID- 17506730
TI  - Nothing new under the sun: the Legacy Project for Anaesthesia.

PMID- 17506731
TI  - Cost effectiveness of adult intensive care in the UK.
AB  - We wished to investigate whether intensive care represents good value for money
      to the National Health Service in the UK using cost-effectiveness analysis. We
      developed a cost-effectiveness model using secondary data sources to estimate the
      incremental cost per quality adjusted life year gained of treatment in intensive
      care vs non-intensive care treatment in adults. Estimates of hospital mortality
      with and without intensive care were obtained from seven published studies and
      from data published by the Intensive Care National Audit and Research Centre.
      Quality of life estimates were obtained from a literature review and NHS
      reference costs were used. Relative to non-intensive care treatment, the
      incremental cost per quality adjusted life year gained of treatment in intensive
      care is 7010 pounds. This figure is sensitive to the mortality risk reduction
      associated with intensive care. Despite the high daily cost of intensive care,
      its cost-effectiveness is excellent and compares favourably with other commonly
      used health interventions. Our findings suggest that adult intensive care
      represents good value for money.

PMID- 17506732
TI  - Comparison of the analgesic efficacy and respiratory effects of morphine,
      tramadol and codeine after craniotomy.
AB  - Pain after craniotomy remains a significant problem. The effect of morphine and
      tramadol patient-controlled analgesia (PCA) on arterial carbon dioxide tension is
      unknown in patients having such surgery. Sixty craniotomy patients were randomly
      allocated to receive morphine PCA, tramadol PCA or codeine phosphate 60 mg
      intramuscularly. Baseline values of pain score (0-10), sedation and arterial
      carbon dioxide tension were recorded at the time of first analgesic
      administration and at 30 min, 1, 4, 8, 12, 18 and 24 h. Patient satisfaction was
      assessed at 24 h. There were no differences in arterial carbon dioxide tension or
      sedation between groups at any time, but in all three groups some patients had
      rises greater than 1 kPa. Morphine produced significantly better analgesia than
      tramadol at all time points (p < 0.005) and better analgesia than codeine at 4,
      12 and 18 h. Patients were more satisfied with morphine than with codeine or
      tramadol (p < 0.001). Vomiting and retching occurred in 50% of patients with
      tramadol, compared with 20% with morphine and 29% with codeine.

PMID- 17506733
TI  - Haemodynamic changes and heart rate variability during midazolam-propofol co
      induction.
AB  - In a prospective, blind, randomised study, we examined the effects of midazolam
      propofol co-induction on haemodynamic (blood pressure, heart rate and stroke
      volume) and heart rate variability. The latter was measured by spectral analysis
      using the maximum-entropy method to calculate the following: the low frequency
      component (LF), which reflects both the cardiac sympathetic and parasympathetic
      activity, the high frequency component (HF) and entropy, which reflects the
      cardiac parasympathetic activity, the total power (TP), calculated by the
      addition of LF and HF, and the LF/HF ratio, which reflects the balance between
      the cardiac sympathetic and parasympathetic nervous activity. Forty patients were
      randomly allocated to the propofol group and the midazolam-propofol group, and
      the parameters described above were calculated at baseline (T1), post induction
      (T2), after tracheal intubation (T3), and 3 min (T4) and 5 min after intubation
      (T5). Propofol was administered at 2.5 mg.kg(-1) in the propofol group and
      midazolam at 0.1 mg.kg(-1) followed by propofol at 1.5 mg.kg(-1) in the midazolam
      propofol group for anaesthesia induction. Then, propofol was administered at 4-6
      mg.kg(-1)propofol for maintenance in both groups. The midazolam-propofol group
      showed compensated haemodynamic changes, which were related to significant
      increases in the LF/HF ratio at T2, T4 and T5 (p = 0.011, 0.038 and 0.034). These
      results suggest that the midazolam-propofol combination yielded compensated
      modulatory effects on the cardiovascular system, including preserved baroreflex
      activity.

PMID- 17506734
TI  - The use of single-use devices in anaesthesia: balancing the risks to patient
      safety.
AB  - Single-use devices are designed, manufactured and sold to be used once and then
      discarded. This paper addresses growing concerns about the quality of some
      devices. Single-use devices, manufactured at a lower cost to justify their
      disposal, are perceived to have a lesser efficacy, which may threaten patient
      safety through iatrogenic harm. There is, in addition, growing scepticism about
      the actual risk of contracting variant Creutzfeldt-Jakob disease and other blood
      borne diseases from reused surgical instruments. Interview data suggests that
      when choosing to use a single-use device, clinicians balance concerns about the
      risk of infection against those about the risk of injury. However, despite
      reservations about induced harm and the unknown risk of an iatrogenic disease,
      most clinicians would want single-use devices used on themselves and their family
      if they were patients.

PMID- 17506735
TI  - Microbial growth in propofol formulations with disodium edetate and the influence
      of venous access system dead space.
AB  - Propofol formulated in lipid supports microbial growth. We hypothesised that
      propofol with disodium edetate would suppress microbial growth more than propofol
      without disodium edetate. We examined bacterial growth in vitro and bacterial
      survival in the dead space of different venous access systems. Bacteria in
      propofol with disodium edetate (Diprivan; AstraZeneca, London, UK) and without
      disodium edetate (1% Propofol inj. 'Maruishi'; Maruishi Pharmaceutical Co. Ltd,
      Osaka, Japan) survived and grew in the dead space of the venous access systems,
      although propofol with disodium edetate suppressed bacterial growth more than
      propofol without. Disodium edetate is effective in retarding microbial growth.
      However, for prevention of healthcare-associated infections, medical
      professionals should maintain strict aseptic precautions when handling propofol,
      use disodium edetate-containing formulations, and should consider using venous
      access systems without dead space.

PMID- 17506736
TI  - Bilateral intra-oral, infra-orbital nerve block for postoperative analgesia
      following cleft lip repair in paediatric patients: comparison of bupivacaine vs
      bupivacaine-pethidine combination.
AB  - This prospective, randomised, double blind study compared the efficacy of
      pethidine as an adjuvant to bupivacaine with the efficacy of bupivacaine alone
      for infra-orbital nerve block in alleviating postoperative pain in children
      undergoing cleft lip repair. Forty paediatric patients aged between 5 and 60
      months undergoing cleft lip repair were randomly allocated to two groups of 20.
      After tracheal intubation, group B received bilateral intra-oral, infra-orbital
      nerve block with 1 ml of 0.25% bupivacaine on each side and group P received 1 ml
      of 0.25% bupivacaine along with 0.25 mg.kg(-1) body weight pethidine. Sedation
      after recovery from anaesthesia was assessed using the University of Michigan
      Sedation Scale (UMSS) and pain was assessed postoperatively up to 36 h using the
      FLACC scale (Face, Legs, Activity, Cry, Consolability). The median (IQR) duration
      of analgesia from the time of administration of block in group B was 18 h (14.2
      20) compared to 29.1 h (24-36) in group P (p = 0.001). Addition of pethidine as
      an adjunct to local anaesthetic significantly prolonged the duration of
      postoperative analgesia without any adverse effects.

PMID- 17506737
TI  - Customer focused incident monitoring in anaesthesia.
AB  - The database of incident forms relating to anaesthesia services in an
      institutional risk management programme were reviewed for 2003-2005, the aim
      being to identify any recurring patterns. Incidents were prospectively
      categorised as relating to attitude/behaviour, communication breakdown, delay in
      service, or were related to care, cost, environment, equipment, security,
      administrative process, quality of service or miscellaneous. The total number of
      anaesthesia-related incidents reported during the period was 287, which related
      to 0.44% of the total number of anaesthetics administered during the time period.
      In all, 170 incidents were reported by the department, 96 by internal customers
      and 21 by external customers. Only 30% of the complaints came from the operating
      room. Thirty-four per cent of all incidents related to communication, behaviour
      and delay in service. A requirement to teach communication skills and stress
      handling formally in anaesthesia training programmes, and at the time of
      induction of staff into the department, has been identified.

PMID- 17506738
TI  - Fibreoptic intubation using three airway conduits in a manikin: the effect of
      operator experience.
AB  - In a randomised cross-over study, 72 anaesthetists (24 Senior House Officers, 24
      Specialist Registrars and 24 Consultants) attempted to place a fibreoptic scope
      in the trachea of a manikin using three airway conduits: the Berman airway, the
      LMA Classic(trade mark) and the intubating laryngeal mask airway. The time for
      insertion of the airway conduit, delivery of two breaths and fibreoptic scope
      placement in the trachea was the primary endpoint. These overall times were
      significantly shorter (median [interquartile range]) using the LMA Classic (36
      [28-45]) than via the intubating laryngeal mask (54 [42-79]) and the Berman
      airway (45 [33-80]), p < 0.0001. Senior House Officers were significantly slower
      than both Specialist Registrars and Consultants (p < 0.0001). The LMA Classic was
      considered to be the easiest conduit to use for fibreoptic scope placement by all
      grades of anaesthetists. We conclude that the LMA Classic is the most effective
      conduit for fibreoptic scope placement especially for anaesthetists with limited
      experience in its use.

PMID- 17506739
TI  - The Airtraq as a rescue airway device following failed direct laryngoscopy: a
      case series.
AB  - We report the successful use of the Airtraq as a rescue device following failed
      direct laryngoscopy, in patients deemed at increased risk for difficult tracheal
      intubation. In a series of seven patients, repeated attempts at direct
      laryngoscopy with the Macintosh blade, and the use of manoeuvres to aid
      intubation, such as the gum elastic bougie placement, were unsuccessful. In
      contrast, with the Airtraq device, each patient's trachea was successfully
      intubated on the first attempt. This report underlines the utility of the Airtraq
      device in these patients.

PMID- 17506740
TI  - Intravenous infusions in hyperbaric chambers: effect of compression on syringe
      function.
AB  - Haemodynamic instability is a recognised phenomenon in critically ill patients
      undergoing hyperbaric therapy. Instability may result from the effects of ambient
      pressure on the cardiovascular system, devices involved in infusion of drugs and
      fluids, or a combination of the two. The effect of hyperbaric pressure on air
      containing spaces in syringes has not been previously measured. We connected 60
      ml syringes (Terumo Corporation, Tokyo, Japan) containing coloured water to low
      volume extensions via three-way taps. We examined the effect of pressurisation to
      2.4 and 2.8 atmospheres absolute (ATA) on the syringes by measuring the
      displacement of the coloured water in the low volume extension set. There was
      compression of air spaces within the syringe causing retrograde flow of fluid
      within the low volume extension set. The mean (95% CI) change in volume was 154
      (141-168) microl at 2.4 ATA, and 197 (183-212) microl at 2.8 ATA (both p <
      0.0001). We conclude that hyperbaric exposure may cause clinically significant
      changes in syringe function at infusion rates < 100 ml. h(-1).

PMID- 17506741
TI  - A randomised controlled trial of the electric heating pad vs forced-air warming
      for preventing hypothermia during laparotomy.
AB  - A randomised controlled trial was conducted to compare the efficacy of upper body
      forced-air warming (Bair Hugger, Augustine Medical model 500/OR, Prairie, MN)
      with that of an electric heating pad (Operatherm 202, KanMed, Bromma, Sweden) for
      maintenance of intra-operative body temperature in 60 patients undergoing
      laparotomy under general anaesthesia. The nasopharyngeal temperature was recorded
      throughout the operative period. The mean (SD) final temperatures were 36.2 (0.4)
      degrees C with forced-air warming and 35.5 (1.0) degrees C with electric heating
      pad (p < 0.01). Upper body forced-air warming is more effective than the heating
      pad for maintenance of body temperature during laparotomy.

PMID- 17506742
TI  - Oxford Miniature Vaporiser output with reversed gas flows.
AB  - This study was undertaken to investigate and calibrate the isoflurane output of
      an Oxford Miniature Vaporiser (OMV) draw-over vaporiser with reversed gas flows.
      Plenum or Boyles type machines have gas flowing left to right through the
      apparatus. Draw over anaesthesia systems, in contrast, traditionally have the
      carrier gas, air plus oxygen, flowing right to left through the vaporiser. There
      are a number of variations in the external design of the OMV vaporiser: 1) a back
      bar mounted draw-over vaporiser with 23-mm taper and left to right gas flow, 2)
      the Tri-Service with 22-mm taper and left to right gas flow, and 3) the
      traditional draw-over OMV with right to left gas flow with a variety of tapers.
      Non-uniformity leads to a variety of possible connections. The predictable output
      of the OMV vaporiser assumes the correct direction of gas flows for the device.
      There are many second hand right to left OMV vaporisers for sale to developing
      countries where the nuances of vaporiser orientation add unnecessarily to the
      desired simplicity of anaesthesia. A simple calibration scale for reversed gas
      flows through the OMV vaporiser would be useful.

PMID- 17506743
TI  - Fatal neuroglycopaenia after accidental use of a glucose 5% solution in a
      peripheral arterial cannula flush system.
AB  - A patient on an Intensive Care Unit who was recovering from multiple organ
      failure was being given an intravenous infusion of insulin to maintain
      normoglycaemia. On her 20th day in the unit, she suddenly became unresponsive. A
      cerebrovascular accident was suspected as other clinical and laboratory
      parameters remained normal apart from a blood glucose value of 20.6 mmol.l(-1).
      The insulin infusion rate had been increased to treat hyperglycaemia. Subsequent
      bedside finger prick blood testing suggested that the blood sugar was low but no
      numerical reading was provided. Repeat blood glucose analysis using a further
      sample drawn from the arterial line and measured in the blood gas analyser gave a
      value of 10.1 mmol.l(-1). Confirmatory laboratory blood tests revealed severe
      hypoglycaemia (0.1 mmol.l(-1)) and intravenous glucose 50% was given immediately.
      Examination showed that a glucose 5% solution had been inadvertently used in the
      arterial cannula flush system rather than saline, contaminating earlier samples
      drawn from the arterial line and giving falsely high blood glucose values. The
      prolonged period of severe hypoglycaemia led to neuroglycopaenia and irreversible
      brain injury. The patient died 9 days later without regaining consciousness. Such
      a complication has not previously been reported in this context and has
      particular significance given the increasing use of insulin therapy to maintain
      normoglycaemia in critically ill patients.

PMID- 17506744
TI  - Inadvertent epidural administration of insulin.
AB  - A 67-year-old female with insulin-dependent diabetes mellitus underwent an
      uncomplicated partial liver resection under combined epidural and general
      anaesthesia. After surgery, 50 U of insulin were accidentally infused into her
      epidural space over a period of 5 h in addition to her prescribed intravenous
      insulin infusion. After recognition of the accidental epidural administration,
      the patient was closely monitored for any neurological signs or symptoms. Blood
      glucose levels decreased significantly from 17.4 to 6.8 mmol.l(-1) over a period
      of 7 h. Despite the hazard of potentially neurotoxic preservatives in the insulin
      preparation, she suffered no neurological sequelae and made an uncomplicated
      recovery.

PMID- 17506745
TI  - Enteral drugs given through a central venous catheter.
AB  - A 74-year-old lady was given verapamil oral solution and a diclofenac dispersible
      tablet through her subclavian central venous catheter instead of her nasogastric
      tube five days after major head and neck surgery. The ensuing respiratory arrest
      resulting from profound ventilation-perfusion mismatch was made harder to manage
      by her potentially difficult airway. Information about the management of enteral
      drugs inadvertently given intravenously is sparse, and this sort of misrouting
      error is likely to be underreported. This case highlights the ease with which
      enteral preparations can be given by the wrong route.

PMID- 17506746
TI  - A case of acute upper and lower airway obstruction due to retropharyngeal
      haemorrhage secondary to acquired haemophilia A.
AB  - We report the first known case of acute upper and lower airway obstruction due to
      retropharyngeal haemorrhage secondary to acquired haemophilia A. The patient
      required tracheal intubation and ventilation followed by surgical tracheostomy,
      prior to transfer to the intensive care unit for management of her coagulopathy
      with recombinant clotting factor products under the care of the haematologists.

PMID- 17506747
TI  - Peri-operative management of diabetes.

PMID- 17506748
TI  - Peri-operative management of diabetes.

PMID- 17506749
TI  - Treatment of neurocardiogenic syncope.

PMID- 17506751
TI  - Pharyngeal packing during ENT surgery.

PMID- 17506753
TI  - Magnesium as an adjuvant during general anaesthesia.

PMID- 17506756
TI  - Midazolam vs ondansetron for preventing postoperative nausea and vomiting.

PMID- 17506757
TI  - Configuration of drawover anaesthetic breathing systems.

PMID- 17506758
TI  - A knotty problem resolved.

PMID- 17506760
TI  - Inadvertent disconnection of the carbon dioxide absorber canister of a Blease
      Frontline anaesthetic machine.

PMID- 17506762
TI  - Blocked catheter mount.

PMID- 17506763
TI  - Malfunctioning gas scavenging unit.

PMID- 17506764
TI  - Incompatibility between blood and Hartmann's solution.

PMID- 17506765
TI  - Preventing confusion due to possibly retained long lines.

PMID- 17506766
TI  - Valsalva manoeuvre for central venous cannulation.

PMID- 17506767
TI  - A simple and cheap training tool for airway endoscopy.

PMID- 17506768
TI  - Securing nasal tubes.

PMID- 17506771
TI  - Effect of angiotensin II type 1 receptor antagonist on tumor growth and
      angiogenesis in a xenograft model of human bladder cancer.
AB  - Several authors have investigated the antitumor activity of angiotensin II type 1
      receptor (AT1R) antagonists, which are widely used as antihypertensive drugs. In
      this study, we evaluated the efficacy of the AT1R antagonist candesartan against
      bladder cancer. For the study in vitro, human bladder cancer cells (KU-19-19)
      were cultured with and without angiotensin II (A II) and candesartan, and cell
      viability and vascular endothelial growth factor (VEGF) secretion were analyzed.
      Also for the study in vivo, a tumor xenograft model was prepared in nude mice
      using KU-19-19 cells. Mice were administered candesartan daily by oral gavage,
      and paclitaxel via intravenous infusion. Microvessel density, VEGF expression,
      and apoptosis were investigated. Candesartan did not induce direct toxicity in KU
      19-19 cells, but VEGF was significantly lower in candesartan-treated cells than
      in the A II-treated control cells. In mice, candesartan, paclitaxel and
      candesartan-paclitaxel significantly suppressed tumor growth to 46.0%, 35.8% and
      17.3%, respectively, of the tumor volume in the control group, showing that
      combined treatment significantly inhibited tumor growth compared to the
      candesartan group. Microvessel density and VEGF were significantly decreased in
      the candesartan and candesartan-paclitaxel groups compared to the control group.
      The apoptotic index was significantly increased in the paclitaxel and candesartan
      paclitaxel groups compared to the control and candesartan groups. In our
      experimental model, candesartan prevented bladder cancer growth by inhibiting
      angiogenesis. Furthermore, combined treatment with candesartan and paclitaxel
      enhanced paclitaxel-induced cytotoxicity. These results suggest that the AT1R
      antagonist candesartan may be a candidate for innovative therapy for bladder
      cancer.

PMID- 17506773
TI  - Establishment and characterization of a cisplatin-resistant cell line (IGSK-1)
      from a poorly differentiated gastric adenocarcinoma.
AB  - We successfully established a spontaneously cisplatin-resistant tumor cell line
      (designated as IGSK-1) derived from original gastric carcinoma. The patient was a
      75-year-old Japanese woman. The histopathological diagnosis was gastric poorly
      differentiated adenocarcinoma accompanied with metastatic foci in lymph nodes,
      pT3, N2 M0, stage IIIB. The IGSK-1 cells grew as adhesive and monolayered
      cultures on the bottom of dishes. The susceptibility of the IGSK-1 cells to anti
      cancer drugs was examined using oxygen electrode apparatus (Daikin, Tsukuba,
      JPN), and the results suggested TXL was effective, and CDDP, CPT-11 and 5-FU were
      not effective. Gastrin and somatostatin secretions were confirmed by
      immunohistochemical staining and also radioimmunoassay. Immunohistochemistry and
      radioimmunoassay for serotonin suggested the IGSK-1 cells might incorporate
      serotonin from the growth media. Spontaneously cisplatin-resistant gastric
      carcinoma cell line secreted gastrin and somatostatin is very important material
      for chemotherapy.

PMID- 17506772
TI  - Plural light chains in a single plasma cell of a monoclonal gammopathy
      undetermined significance case: an ultrastructural study.
AB  - A 44-year-old man was found to have M-proteins of IgG consisting of kappa- and
      lambda-chains in serum without lymphadenopathy or splenomegaly. The serum
      concentrations of IgG, IgA and IgM were within normal limits. Bone marrow
      examination showed normal cellular marrow containing 6.3% of plasma cells with no
      abnormal features. No chromosomal abnormality was observed at all. The patient
      was diagnosed as having monoclonal gammopathy of undetermined significance. The
      bone marrow plasma cells possessed free kappa- and lambda-chains in Golgi
      apparatus, rough endoplasmic reticula and cytoplasmic matrices. Plural light
      chains were simultaneously produced with the same heavy chain in a plasma cell by
      immunoelectron microscopy. This is the first report in the world of a monoclonal
      gammopathy of undetermined significance producing plural light chains with the
      same heavy chain.

PMID- 17506774
TI  - Interleukin 6 variable number of tandem repeats (VNTR) gene polymorphism in
      centenarians.
AB  - Recent population-based studies identified the magnitude of interleukin 6 (IL6)
      serum levels as a marker for functional disability, and a predictor of disability
      and mortality among the elderly. We investigated whether there was evidence in
      Southern Italy of an association between the IL6 gene variable number of tandem
      repeats (VNTR) polymorphism and extreme longevity, and tested for the possible
      interaction of apolipoprotein E (APOE) alleles with the IL6 VNTR alleles. Four
      alleles coding for variants of four different lengths have been identified:
      allele A [760 base pairs (bp)], allele B (680 bp), allele C (640 bp), and allele
      D (610 bp). IL6 VNTR and APOE allele and genotype frequencies were studied in a
      total of 61 centenarians and 94 middle-aged subjects from Southern Italy. The IL6
      VNTR allele B was overrepresented in the younger control group compared with
      centenarians (odds ratio: 0.56, 95% confidence interval: 0.35-0.88, Bonferroni p
      value < 0.05). No interactions between IL6 VNTR alleles and APOE alleles on the
      odds ratios to reach extreme longevity were evaluated for the smallest number of
      subjects in centenarians and younger controls. Our findings suggested that the
      presence of the IL6 VNTR allele B could be detrimental for reaching extreme
      longevity.

PMID- 17506775
TI  - A comparison of two different techniques for oculomotor torque reduction.
AB  - PURPOSE: To compare the results of two different surgical techniques: 'Cuppers
      technique', in which the torque of oculomotor rectus muscles is reduced by
      suturing the muscle to the globe in the posterior half of the globe; and 'Y-split
      recessions', in which the muscle torque is reduced by Y-splitting the rectus
      muscles, and reattaching the two halves at an angle to each other. METHODS: We
      carried out a retrospective analysis of the outcome of surgery on 100 patients
      with infantile esotropia. RESULTS: Both techniques show a sufficient reduction of
      strabismus angle variability, and minimal and maximal strabismus angle.
      CONCLUSIONS: Both techniques achieve satisfactory results. In addition, the Y
      split technique allows for accurate control of the muscle torque and requires no
      access to the posterior half of the eye, which can facilitate the surgical
      approach. For a reduction in muscle torque, the Y-split recession is a good
      alternative to the established Cuppers technique.

PMID- 17506776
TI  - Abstracts of the 5th joint meeting of the German, Austrian, and Swiss Sections of
      the International League Against Epilepsy, Basle, May 16-19, 2007.

PMID- 17506777
TI  - Cardiovascular toxicity due to metoprolol poisoning in a patient with coronary
      artery disease.
AB  - AIM: To demonstrate that beta-blocker poisoning results in cardiovascular and
      central nervous system findings. METHODS: A 56-year-old woman was brought to the
      emergency department, having been admitted to hospital with 1500 mg of metoprolol
      ingestion 2 h previously. She had undergone percutaneous transluminal coronary
      angioplasty and stenting because of acute myocardial infarction (AMI). Her ECG
      revealed ST segment elevation in inferior leads and junctional dysrhythmia. Her
      clinical symptoms relieved after pacing and hospitalization and she was
      discharged. RESULTS: Our patient demonstrated findings of AMI with hypotension
      and bradycardia that appeared to result from metoprolol poisoning. Although one
      patient has been reported to have AMI associated with metoprolol poisoning, our
      patient is unique with her ECG changes and elevated cardiac markers: this is the
      first time that AMI characterized by elevated cardiac markers associated with
      metoprolol toxicity has been reported. CONCLUSIONS: Emergency physicians should
      bear in mind that AMI can accompany the presentation of metoprolol overdose in
      those with coronary artery disease. In other words, metoprolol poisoning can
      trigger myocardial ischaemia and dysrhythmia in those with coronary artery
      disease.

PMID- 17506778
TI  - A pharmacokinetic model for L-carnitine in patients receiving haemodialysis.
AB  - AIMS: Patients requiring chronic haemodialysis may develop a secondary carnitine
      deficiency through dialytic loss of L-carnitine. A previous report has described
      the plasma concentrations of L-carnitine in 12 such patients under baseline
      conditions and after L-carnitine administration (20 mg kg(-1)). A three
      compartment pharmacokinetic model was developed to describe these data to make
      inferences about carnitine supplementation in these patients. METHODS: L
      carnitine removal was mediated solely by intermittent haemodialysis, which was
      incorporated into the model as an experimentally derived dialysis clearance value
      that was linked to an on-off pulse function. Data were described by a model with
      a central compartment linked to 'fast'- and 'slow'-equilibrating peripheral
      compartments. RESULTS: The model adequately described the changing plasma
      concentrations of endogenous L-carnitine in individual haemodialysis patients.
      Based on pooled data (mean +/- SD; n = 12), the volume of the central compartment
      was 10.09 +/- 0.72 l and the transfer rate constants into and out of the slowly
      equilibrating pool were 0.100 +/- 0.018 h(-1) and 0.00014 +/- 0.00016 h(-1),
      respectively. The turnover time of L-carnitine in the slow pool (which was
      assumed to represent muscle) was approximately 300 days. The model was in general
      agreement with separate data on the measured loss of carnitine from muscle in
      dialysis patients. CONCLUSIONS: Haemodialysis causes rapid reductions in plasma L
      carnitine concentrations with each dialysis session. Plasma concentrations are
      restored between sessions by redistribution from peripheral compartments.
      However, during chronic haemodialysis, the ongoing dialytic loss of L-carnitine
      may lead to a slow depletion of the compound, contributing to a possible
      secondary deficiency.

PMID- 17506779
TI  - Foundation year 1 doctors and clinical pharmacology and therapeutics teaching. A
      retrospective view in light of experience.
AB  - AIMS: To determine whether, in retrospect, first year foundation (FY1) programme
      doctors believe that their undergraduate education in Clinical Pharmacology and
      Therapeutics (CPT) has prepared them to prescribe safely and rationally. METHODS:
      This was a prospective questionnaire survey. Ninety FY1 doctors, employed in the
      Aberdeen Teaching Hospitals, participated. RESULTS: Seventy-one percent of FY1
      doctors completed the survey. Thirty percent of respondents rated their knowledge
      of CPT as poor or worse and only 8% as good; 74% reported having witnessed an
      adverse drug reaction (ADR) and 55% a drug-drug interaction, a number of which
      had resulted in patient morbidity or mortality. Many of these events were
      reported to have been avoidable or predictable with more extensive undergraduate
      and postgraduate training. Forty-two percent of respondents stated that they had
      not been taught enough about avoiding ADRs and 60% about avoiding drug-drug
      interactions during their undergraduate years. Over 75% of respondents reported
      high levels of confidence for the unsupervised use of warfarin, nonsteroidal
      analgesics and opiate analgesics. In retrospect, FY1 doctors would like more
      undergraduate teaching in prescribing for special patient groups, ADRs, drug
      interactions, together with CPT in their postgraduate teaching programme.
      CONCLUSIONS: FY1 doctors believe that their undergraduate and postgraduate
      training in CPT is insufficient to prescribe safely and rationally. This study
      adds further weight to the call for an increase in the training of junior doctors
      in the rational and safe use of medicines.

PMID- 17506780
TI  - Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus
      in healthy volunteers.
AB  - AIM: To assess the effect of Schisandra sphenanthera extract (SchE) on the
      pharmacokinetics of tacrolimus in healthy volunteers. METHODS: Twelve healthy
      male volunteers were orally treated with SchE, three capsules twice daily for 13
      days. Pharmacokinetic investigations of oral tacrolimus administration at 2 mg
      were performed both before and at the end of the SchE treatment period. Whole
      blood tacrolimus concentrations were determined by enzyme-linked immunosorbent
      assay. Estimated pharmacokinetic parameters before and with SchE were calculated
      with noncompartmental techniques. RESULTS: Following administration of SchE, the
      average percentage increases of individual increases in AUC, AUMC and C(max) of
      tacrolimus were 164.2% [95% confidence interval (CI) 70.1, 258.4], 133.1% (95% CI
      49.5, 261.3) and 227.1% (95% CI 155.8, 298.4), respectively (P < 0.01 or 0.05).
      On average, there was a 36.8% (95% CI 13.4, 60.2) increase in tacrolimus t(max)
      (P < 0.01). The average percentage decreases in CL/F and V/F were 49.0% (95% CI
      31.1, 66.9) and 53.7% (95% CI 40.1, 67.4), respectively (P < 0.01). CONCLUSIONS:
      SchE can increase the oral bioavailability of tacrolimus. The results of this
      study will add important information to the interaction area between drugs and
      herbal products.

PMID- 17506781
TI  - Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated
      with melatonin.
AB  - AIM: Since melatonin is antioxidant and has some anti-inflammatory actions, we
      have tested it as adjunctive treatment in patients with rheumatoid arthritis, to
      determine whether it can improve patients' symptoms. METHODS: A total of 75
      patients were allocated randomly to receive melatonin 10 mg at night in addition
      to ongoing medication, or a placebo of identical appearance. Monthly blood
      samples were taken and disease severity assessed over 6 months, plasma being
      analysed for inflammatory indicators [C-reactive protein, erythrocyte
      sedimentation rate (ESR), neopterin], proinflammatory cytokines [interleukin (IL)
      1beta, IL-6, tumour necrosis factor (TNF)-alpha], lipid peroxidation products and
      the kynurenine pathway metabolites of tryptophan. RESULTS: An increase of ESR
      (two-way anova F((1,127)) = 5.24, P = 0.024) and neopterin concentrations
      (F((1,136)) = 4.64, P = 0.033) was observed in treated patients compared with
      controls, reflected also in a significant trend for both to decline in placebo
      treated patients (P = 0.022), but not the melatonin-treated group. Peroxidation
      products showed a significant trend to decrease in placebo- but not melatonin
      treated patients. These results suggest a proinflammatory action, but there were
      no significant effects of melatonin treatment on clinical assessments of patient
      symptoms or the concentrations of three proinflammatory cytokines, IL-1beta, IL-6
      and TNF-alpha. Melatonin significantly increased plasma kynurenine concentrations
      (F((1,124)) = 4.24, P = 0.041), again suggesting proinflammatory activity.
      CONCLUSION: A daily dose of 10 mg melatonin shows a slowly developing antioxidant
      profile in patients with arthritis and increases the concentrations of some
      inflammatory indicators, but these effects are not associated with any change of
      proinflammatory cytokine concentrations or clinical symptoms.

PMID- 17506782
TI  - Risk of congenital anomalies in pregnant users of statin drugs.
AB  - AIMS: Evidence from animal studies suggests that statin medications should not be
      taken during pregnancy. Our aim was to examine the association between the use of
      statins in early pregnancy and the incidence of congenital anomalies. METHODS: A
      population-based pregnancy registry was built. Three study groups were assembled:
      women prescribed statins in the first trimester (group A), fibrate/nicotinic acid
      in the first trimester (group B) and statins between 1 year and 1 month before
      conception, but not during pregnancy (group C). Among live-born infants, we
      selected as cases infants with any congenital anomaly diagnosed in the first year
      of life. Controls were defined as infants with no congenital anomalies. The rate
      of congenital anomalies in the respective groups was calculated. Adjusted odds
      ratios (OR) and 95% confidence intervals (CI) were also calculated. RESULTS: Our
      study group consisted of 288 pregnant women. Among women with a live birth, the
      rate of congenital anomalies was 3/64 (4.69%; 95% CI 1.00, 13.69) in group A,
      3/14 in group B (21.43%; 95% CI 4.41, 62.57) and 7/67 in group C (10.45%; 95% CI
      4.19, 21.53). The adjusted OR for congenital anomalies in group A compared with
      group C was 0.36 (95% CI 0.06, 2.18). CONCLUSION: We did not detect a pattern in
      fetal congenital anomalies or evidence of an increased risk in the live-born
      infants of women filling prescriptions for statins in the first trimester of
      pregnancy. Conclusions, however, remain uncertain in the absence of data from non
      live births.

PMID- 17506783
TI  - Ergotamine treatment during pregnancy and a higher rate of low birthweight and
      preterm birth.
AB  - AIMS: Previously the association between oral ergotamine treatment during
      pregnancy and gestational age at delivery, birthweight, the rate of preterm birth
      and low birthweight has not been studied. METHODS: Newborn infants without
      congenital abnormalities born to mothers with or without ergotamine treatment
      during pregnancy were evaluated in the population-based data set of the Hungarian
      Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996.
      RESULTS: Of 38,151 newborn infants with medically recorded gestational age and
      birth weight, 77 were born to mothers who had received ergotamine treatment
      during pregnancy. A statistically significant decrease was found in the mean
      gestational age (0.7 weeks) and birth weight (196 g) among exposed relative to
      unexposed infants, though these differences were not obstetrically significant.
      However, there was a significant increase in the proportion of low birthweight
      newborns (16.4% vs. 5.7%) and preterm births (16.4% vs. 9.2%) after the use of
      ergotamine during pregnancy. The effect of ergotamine was more obvious in male
      newborn infants, particularly after treatment in the third trimester.
      CONCLUSIONS: The association between low birthweight and/or preterm birth and
      ergotamine treatment may be connected with the effect of ergotamine on the
      placenta of pregnant women.

PMID- 17506784
TI  - Detecting signals of drug-drug interactions in a spontaneous reports database.
AB  - AIMS: The spontaneous reports database is widely used for detecting signals of
      ADRs. We have extended the methodology to include the detection of signals of
      ADRs that are associated with drug-drug interactions (DDI). In particular, we
      have investigated two different statistical assumptions for detecting signals of
      DDI. METHODS: Using the FDA's spontaneous reports database, we investigated two
      models, a multiplicative and an additive model, to detect signals of DDI. We
      applied the models to four known DDIs (methotrexate-diclofenac and bone marrow
      depression, simvastatin-ciclosporin and myopathy, ketoconazole-terfenadine and
      torsades de pointes, and cisapride-erythromycin and torsades de pointes) and to
      four drug-event combinations where there is currently no evidence of a DDI
      (fexofenadine-ketoconazole and torsades de pointes, methotrexade-rofecoxib and
      bone marrow depression, fluvastatin-ciclosporin and myopathy, and cisapride
      azithromycine and torsade de pointes) and estimated the measure of interaction on
      the two scales. RESULTS: The additive model correctly identified all four known
      DDIs by giving a statistically significant (P < 0.05) positive measure of
      interaction. The multiplicative model identified the first two of the known DDIs
      as having a statistically significant or borderline significant (P < 0.1)
      positive measure of interaction term, gave a nonsignificant positive trend for
      the third interaction (P = 0.27), and a negative trend for the last interaction.
      Both models correctly identified the four known non interactions by estimating a
      negative measure of interaction. CONCLUSIONS: The spontaneous reports database is
      a valuable resource for detecting signals of DDIs. In particular, the additive
      model is more sensitive in detecting such signals. The multiplicative model may
      further help qualify the strength of the signal detected by the additive model.

PMID- 17506785
TI  - The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate,
      a new oral direct thrombin inhibitor, in healthy male subjects.
AB  - AIMS: The novel direct thrombin inhibitor (DTI), dabigatran etexilate (Boehringer
      Ingelheim Pharma GmbH & Co. KG), shows potential as an oral antithrombotic agent.
      Two double-blind, randomized trials were undertaken to investigate the
      pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of orally
      administered dabigatran etexilate in healthy male subjects. METHODS: Dabigatran
      etexilate or placebo was administered orally at single doses of 10-400 mg (n =
      40) or at multiple doses of 50-400 mg three times daily for 6 days (n = 40).
      Plasma and urine samples were collected over time to determine the PK profile of
      dabigatran. PD activity was assessed by its effects on blood coagulation
      parameters: activated partial thromboplastin time (aPTT), prothrombin time (PT),
      reported as international normalized ratio (INR), thrombin time (TT), and ecarin
      clotting time (ECT). All adverse events were recorded. RESULTS: Dabigatran
      etexilate was rapidly absorbed with peak plasma concentrations of dabigatran
      reached within 2 h of administration. This was followed by a rapid
      distribution/elimination phase and a terminal phase, with associated estimated
      half-lives of 8-10 h and 14-17 h with single and multiple dose administrations,
      respectively. Dabigatran exhibited linear PK characteristics with dose
      proportional increases observed in maximum plasma concentration and area under
      the curve. Steady-state conditions were reached within 3 days with multiple
      dosing. The mean apparent volume of distribution during the terminal phase
      (V(z)/F) of 1860 l (range 1430-2400 l) and the apparent total clearance after
      oral administration (CL(tot)/F) of 2031 ml min(-1) (range 1480-2430), were dose
      independent. Time curves for aPTT, INR, TT and ECT paralleled plasma
      concentration-time curves with values increasing rapidly and in a dose-dependent
      manner. At the highest dose of 400 mg administered three times daily, maximum
      prolongations over baseline of 3.1 (aPTT), 3.5 (INR), 29 (TT) and 9.5-fold (ECT)
      were observed. Dabigatran underwent conjugation with glucuronic acid to form
      pharmacologically active conjugates that accounted for approximately 20% of total
      dabigatran in plasma. Overall, variability in PK parameters was low to moderate,
      with an average interindividual coefficient of variation (CV) of approximately
      30% and variability in PD parameters was low, with CV < 10%. Of the four assays,
      TT and ECT exhibited the greatest sensitivity and precision within the
      anticipated therapeutic dose range. Bleeding events were few and were mild-to
      moderate in intensity, occurring only in the higher, multiple dose groups.
      CONCLUSIONS: These data suggest that dabigatran etexilate is a promising novel
      oral DTI with predictable PK and PD characteristics and good tolerability.
      Further investigation of dabigatran etexilate for the treatment and prophylaxis
      of patients with arterial and venous thromboembolic disorders, acute coronary
      syndromes and other medical conditions is warranted.

PMID- 17506786
TI  - Development of oral anticoagulants.

PMID- 17506787
TI  - Skin manifestations of intravascular lymphoma mimic inflammatory diseases of the
      skin.
AB  - BACKGROUND: Intravascular lymphoma (IVL) is fatal when it is diagnosed late in
      the course. Sometimes skin lesions enable early diagnosis, but criteria for
      diagnosis are not well established. OBJECTIVES: To demonstrate the clinical
      spectrum of skin lesions of IVL and to correlate it with clinical outcome; to
      identify features differentiating between B-cell and T-cell IVL with skin
      involvement. METHODS: Review of 97 articles reporting on total of 224 patients
      with IVL. RESULTS: Skin lesions were mentioned in 90 of 224 patients. They were
      nodules and/or plaques (49%) or macules (22.5%) of red (31%) or blue to livid
      (19%) colour on the leg (35%), the thigh (41%) and the trunk (31%).
      Telangiectases were present in only 20% of the patients. Oedema (27.5%) of the
      legs and pain (24%) were often accompanying. No criteria enabled distinction
      between lesions restricted to the skin and skin lesions concurrent with IVL in
      other organs, but when the disease was restricted to the skin, the prognosis was
      favourable (10% vs. 85% fatal outcome). Skin lesions of T-cell IVL are
      indistinguishable from those of B-cell IVL. CONCLUSIONS: Forty per cent of all
      patients with IVL have skin lesions, these being red, sometimes painful plaques
      located typically on the lower extremities, accompanied by oedema. A clinician
      risks misinterpreting these changes as thrombophlebitis, erythema nodosum or
      erysipelas. Neither clinical course nor differentiation of the lymphoma can be
      predicted from the morphology of skin lesions, but involvement of other organs at
      the time of diagnosis indicates a poor prognosis.

PMID- 17506788
TI  - Concurrent oxytocin with dinoprostone pessary versus dinoprostone pessary in
      labour induction of nulliparas with an unfavourable cervix: a randomised placebo
      controlled trial.
AB  - OBJECTIVE: To compare concurrent oxytocin with dinoprostone pessary versus
      dinoprostone pessary in labour induction for nulliparas with an unfavourable
      cervix. DESIGN: A randomised double-blind study. SETTING: University Malaya
      Medical Centre, Malaysia. POPULATION: Nulliparas at term with intact membranes,
      Bishop score < or = 6 and admitted for labour induction. METHODS: All women
      received 3 mg dinoprostone pessary for labour induction. Those randomised to the
      oxytocin arm received oxytocin infusion started at 1 micro/minute and doubled
      every 30 minutes to a maximum 16 micro/minute. Women assigned to placebo received
      identical volume of saline infusion. After 6 hours, infusion was stopped and
      vaginal reassessment performed to guide further management. MAIN OUTCOME
      MEASURES: Primary outcome was vaginal delivery within 24 hours. RESULTS:
      Concurrent oxytocin infusion with dinoprostone pessary did not significantly
      increase vaginal delivery rate within 24 hours (48.6 versus 35.9%; P = 0.07,
      relative risk [RR] 1.4 [95% CI 1.0-1.9]). It reduced the requirement for repeat
      dinoprostone (37.1 versus 61.2%; P = 0.001, RR 0.61 [95% CI 0.45-0.81]) and
      improved maternal satisfaction with the birth process (median score of 3 versus 5
      on a 10-point visual analogue scale, P = 0.007). Caesarean rates were not
      different (41.9 versus 44.7%, P = 0.52). CONCLUSIONS: Labour induction with
      concurrent oxytocin infusion and vaginal dinoprostone could be considered for
      nulliparas with an unfavourable cervix. Larger studies are needed.

PMID- 17506789
TI  - Aromatherapy in childbirth: a pilot randomised controlled trial.
AB  - OBJECTIVES: We aimed to determine the feasibility of conducting a randomised
      controlled trial (RCT) on the use of aromatherapy during labour as a care option
      that could improve maternal and neonatal outcomes. DESIGN: RCT comparing
      aromatherapy with standard care during labour. SETTING: District general
      maternity unit in Italy. SAMPLE: Two hundred and fifty-one women randomised to
      aromatherapy and 262 controls. METHODS: Participants randomly assigned to
      administration of selected essential oils during labour by midwives specifically
      trained in their use and modes of application. MAIN OUTCOME MEASURES: Intrapartum
      outcomes were the following: operative delivery, spontaneous delivery, first- and
      second-stage augmentation, pharmacological pain relief, artificial rupture of
      membranes, vaginal examinations, episiotomy, labour length, neonatal wellbeing
      (Apgar scores) and transfer to neonatal intensive care unit (NICU). RESULTS:
      There were no significant differences for the following outcomes: caesarean
      section (relative risk [RR] 0.99, 95% CI: 0.70-1.41), ventouse (RR 1.5, 95% CI:
      0.31-7.62), Kristeller manoeuvre (RR 0.97, 95% CI: 0.64-1.48), spontaneous
      vaginal delivery (RR 0.99, 95% CI: 0.75-1.3), first-stage augmentation (RR 1.01,
      95% CI: 0.83-1.4) and second-stage augmentation (RR 1.18, 95% CI: 0.82-1.7).
      Significantly more babies born to control participants were transferred to NICU,
      0 versus 6 (2%), P = 0.017. Pain perception was reduced in aromatherapy group for
      nulliparae. The study, however, was underpowered. CONCLUSION: This study
      demonstrated that it is possible to undertake an RCT using aromatherapy as an
      intervention to examine a range of intrapartum outcomes, and it provides useful
      information for future sample size calculations.

PMID- 17506790
TI  - Chronic hydrocephalus: a treatable cause of primary amenorrhoea.

PMID- 17506791
TI  - Change in heart rate variability in relation to a significant ST-event associates
      with newborn metabolic acidosis.
AB  - OBJECTIVE: To find whether low-to-high frequency (LF/HF) ratio of fetal heart
      rate (FHR) variability changes in relation to a significant ST-event during
      delivery, and if the change is predictive of metabolic acidosis of the newborn.
      DESIGN: A case-control study. SETTING: Data from a multicentre project. SUBJECTS:
      Acidotic and control fetuses with abnormal cardiotocography together with a ST
      event in fetal electrocardiogram (ECG). METHODS: We studied intrapartum FHR
      variability with spectral analysis from 34 fetuses with a significant ST-event in
      the fetal ECG. LF/HF ratio of FHR variability was measured within a period of 1
      hour before and 1 hour after a significant ST-event. Sensitivity and specificity
      of the change in LF/HF ratio of FHR variability in prediction of metabolic
      acidosis (pH < or = 7.05 and base deficit value > 12.0 mmol/l) of the newborn
      were described by means of the receiver operating characteristic curve. MAIN
      OUTCOME MEASURES: Change in LF/HF ratio of FHR in relation to a significant ST
      event. RESULTS: We found that a relative change in LF/HF ratio greater than 30%
      in relation to a significant ST-event predicted cord arterial metabolic acidosis
      with a sensitivity of 89% (95% CI 68-100%) and specificity of 80% (95% CI 64
      96%). CONCLUSIONS: Relative changes in LF/HF ratio of FHR variability in relation
      to a significant ST-event are more pronounced in fetuses born with metabolic
      acidosis.

PMID- 17506792
TI  - Maternal mortality in Yunnan, China: recent trends and associated factors.
AB  - OBJECTIVE: Yunnan Province, located in southwest China, is one of the poorest
      province in China. The maternal mortality ratio (MMR) is about twice the national
      average (56.2/100,000 live births), and in remote mountainous regions, the rate
      is five times higher. This study aimed to examine the progress in reduction of
      maternal mortality in the 1990s and early 2000s and the factors associated with
      this reduction in Yunnan. DESIGN: A population-based, longitudinal, ecological
      correlation study. SETTING: A remote province of China with a proportionately
      large indigenous population. POPULATION: Populations at county, prefecture and
      provincial level. METHODS: Using maternal mortality data collected at the
      province, prefecture/region and county levels, trend and time series analyses and
      multivariate linear regression analyses were performed using SPSS (Version 13).
      MAIN OUTCOME MEASURE: MMR and its change over time. RESULTS: MMR declined
      substantially in the 1990s at a rate of 3.0% per year. Utilisation of prenatal
      and obstetric care increased and was significantly correlated with the declining
      trend in MMR. Hospital delivery was a strong predictor of MMR, independent of
      social and economic development. Both low income and illiteracy were
      significantly associated with increased MMR. CONCLUSIONS: Declines in maternal
      mortality in Yunnan over the past 14 years appear to reflect health, social and
      economic interventions implemented in the 1990s. The association of hospital
      delivery with maternal mortality may be due to the effective management of severe
      pregnancy and birth complications. Low income and illiteracy were associated with
      MMR but primarily through their impact on the use of prenatal and obstetric care.

PMID- 17506793
TI  - Obstetric fistulae: a study of women managed at the Monze Mission Hospital,
      Zambia.
AB  - OBJECTIVE: The objective of this study was to describe and compare
      characteristics of women with obstetric fistula. DESIGN: Retrospective cross
      sectional study. SETTING: Zambia's primary fistula repair centre, Monze Mission
      Hospital. SAMPLE: All women, August 2003 to December 2005. METHOD: Review of case
      notes to obtain data on socio-demographic and obstetric characteristics,
      causative pregnancy, clinical details, and treatment. Comparison of
      characteristics with national data was undertaken. RESULTS: Of 259 women, 239 had
      socio-demographic and obstetric records and 254 had surgical records. Educational
      status and height of women were significantly below the national averages, while
      antenatal care uptake (97.5%) and proportion from the Northern Province were
      significantly above. Most women (77.9%) weighed < or = 50 kg. Median age at
      marriage was 18 and at development of fistula was 22 years. 15.1% of women were
      divorced, 49.0% were primiparous, and 27.6% were parity four +. 67.5% of women
      had spent 2 days or longer in labour. Delays in receiving emergency obstetric
      care (EmOC) were experienced at home (67.5%) and at clinics (49.4%), usually due
      to transport difficulties. 89.1% delivered in a health facility, 50.2% of
      deliveries were by caesarean section, and 78.1% of babies were stillborn. 72.9%
      of repairs were successful, 17.3% resulted in residual stress incontinence, and
      9.8% failed. Failure was significantly associated with previous repair.
      CONCLUSION: More obstetric fistulae occur in areas where early marriage and
      pregnancy before pelvic maturity is attained is common and where obstetric care
      is inaccessible. In this study, age at marriage and fistula development was older
      than usually found, which may indicate that poor access to EmOC contributes more
      to this problem within Zambia.

PMID- 17506794
TI  - Proteomics-based identification of alpha-enolase as a tumor antigen in non-small
      lung cancer.
AB  - Autoantibodies against tumor antigens represent one type of biomarker that may be
      assayed in serum for detection of cancer and monitoring of disease progression.
      In the present study, we used a proteomics-based approach to identify novel tumor
      antigens in non-small cell lung cancer (NSCLC). By combining two-dimensional
      electrophoresis, western blotting, mass spectrometry and enzyme-linked
      immunosorbent assay technology, we detected autoantibodies against alpha-enolase
      in a subset of NSCLC patients' sera. When 'Mean OD(healthy control sera) + 3
      SD(healthy control sera)' was used as the cut-off point, the prevalence of this
      autoantibody was 27.7% in patients with NSCLC (26 of 94), 1.7% in healthy control
      subjects (1 of 60), and not detectable in sera from 15 patients with small cell
      lung cancer, 18 patients with gastrointestinal cancer and nine patients with
      Mycobacterium avium complex infection of lung. Immunohistochemical staining
      showed that expression of alpha-enolase was increased in cancer tissues of NSCLC
      patients, and flow cytometric analysis confirmed the expression of alpha-enolase
      at the surface of cancer cells. The combined detection of autoantibodies against
      alpha-enolase, carcinoembryonic antigen and cytokeratin 19 fragment (CYFRA21-1)
      enhanced sensitivity for the diagnosis of NSCLC. Therefore, autoantibodies
      against alpha-enolase may constitute a promising biomarker for NSCLC.

PMID- 17506795
TI  - The effect of epidural analgesia on postoperative outcome after colorectal
      surgery.
AB  - OBJECTIVE: The aim of this review was to determine the effects of epidural
      analgesia as it relates to outcome after colorectal surgery. METHOD: We searched
      and reviewed studies that included colorectal surgery and epidural method of
      analgesia listed on the Pubmed, Medline, Embase and the Cochrane library
      database. RESULTS: The majority of data demonstrate a superior effect of epidural
      analgesia on pain control after colorectal surgery. Well designed randomized
      controlled trials (RCT's) have also shown that epidural analgesia reduces the
      duration of ileus after colorectal surgery. Limited data suggest the additional
      benefit may be minimal after laparoscopic surgery or when epidural analgesia is
      used as part of a multimodal regime. Data does not convincingly show either a
      clear harmful or beneficial effect of epidural analgesia on rates of anastomotic
      leakage. Epidural analgesia may have beneficial effects on postoperative lung
      function, however due to low numbers, the effects on cardiovascular and
      thromboembolic complications are indeterminate. Length of hospital stay has not
      been shown to be shortened by sole use of an epidural and, although epidural
      analgesia may be apparently more costly, alternatives may incur higher indirect
      costs and decreased patient satisfaction. CONCLUSION: Randomized controlled
      trials have shown a benefit for epidurals on postoperative pain relief, and
      ileus, and possibly respiratory complications. There is no proven benefit with
      regard to length of stay. There are a number of unresolved issues which further
      focussed RCT's may help clarify such as effects of epidural on complication rates
      after colorectal surgery.

PMID- 17506797
TI  - Multiple red-brown papules in an elderly man.

PMID- 17506796
TI  - A 6-year review of surgical morbidity and oncological outcome after high anterior
      resection for colorectal malignancy with and without splenic flexure
      mobilization.
AB  - OBJECTIVE: High anterior resection (HAR) for colorectal cancer is traditionally
      performed with routine mobilization of the splenic flexure. This is a
      retrospective review of mortality and morbidity following HAR in which the
      splenic flexure has been preserved. METHOD: From a prospective database, all
      patients who had undergone elective HAR for colorectal cancer between 1999 and
      2005 were identified. Morbidity, mortality, pathology and survival data for
      patients having HAR with and without splenic flexure mobilization were analysed.
      RESULTS: A total of 707 patients were identified. Five hundred and thirty-one had
      HAR with preservation of the splenic flexure. In these patients outcome was:
      anastomotic leak (0.4%), wound infection (3.6%), anastomotic stricture (0.4%) and
      30-day mortality (0.9%). No statistical significant difference was found for
      postoperative morbidity (P = 0.1926), 30-day mortality (P =0.3285), lymph node
      harvest (P = 0.2127) or survival (P = 0.1457) compared with patients in whom the
      splenic flexure was mobilized. Longitudinal resection margins were greater
      following HAR with splenic flexure mobilization (P < 0.0001). CONCLUSION: No
      morbidity, oncological or survival disadvantage in performing splenic flexure
      preserving HAR was found.

PMID- 17506798
TI  - Bovine follicular fluid contains antagonist activity for cumulus expansion
      promoting effect by epidermal growth factor.
AB  - The present study was conducted to investigate the effects of bovine follicular
      fluid (bFF) fractions or epidermal growth factor (EGF) on cumulus cell expansion
      in bovine cumulus-oocyte complexes (COCs) in vitro. bFF derived from large
      follicles (15-20 mm) and its fractions (>100, 10-100 and <100 kDa) were added to
      the medium. Cumulus cell expansion was stimulated when COCs were incubated with
      the 10-100 and <100 kDa fractions or bFF; in contrast, the culture of COCs with
      the >100 kDa fraction resulted in the suppression of cumulus cell expansion.
      Although the >100 kDa fraction prohibited the expansion of cumulus cells in the
      medium with or without low concentration EGF, cumulus expansion was promoted when
      COCs were cultured with the >100 kDa fraction and high-concentration EGF. In
      conclusion, the results suggest that bFF contains promoting and inhibiting effect
      for expansion of cumulus cells in COCs in vitro. The inhibiting effect of bFF may
      act antagonistically against the effect of EGF for the event of expanding cumulus
      cells.

PMID- 17506799
TI  - Age, FSH dose and follicular aspiration frequency affect oocyte yield from
      juvenile donor lambs.
AB  - Experiments were conducted to determine the effects of lamb age, frequency of
      follicular aspirations, and hormone stimulation by fixed or variable FSH dose, on
      the number of collected oocytes and their maturational competence. In trial 1,
      the characteristics of follicular population (number and diameter of follicles)
      were studied in 40 lambs which were slaughtered at the age of 30 days (S1), 42
      days (S2), 60 days (S3) and 5-6 months (S4), each n = 10. In trial 2, 27 lambs
      were divided into four groups. group MF lambs (n = 6) had follicular aspiration
      (OPU) in four monthly intervals commencing from the age of 8-9 weeks (sessions
      MF1, MF2, MF3 and MF4). In groups SF2, SF3 and SF4 (each n = 6), OPU was
      conducted once during the 12-13, 16-17 and 20-21 week of age, respectively.
      Ovarian stimulation was conducted with fixed FSH dose (3.52 mg/animal). In trial
      3, 10 lambs (group MV) were treated as those of group MF apart from the FSH dose,
      which was administered according to the body weight in a dose of 0.27 mg/kg. The
      number and the size of follicles, the number and the quality of collected oocytes
      and the maturational competence of the oocytes were compared between and within
      groups. In trial 1, the total number and the number of small follicles were
      greater in groups S1 and S2 compared with those of S3 and S4 (p < 0.01).
      Similarly, the follicular population was greater in group MF1 than in group SF3
      (p < 0.01). In sessions MF2, MF3, MV2, MV3 and MV4, more oocytes were collected
      in comparison with those from the respective once-aspirated age mates (groups
      SF2, SF3 and SF4). In total, more (p = 0.02) oocytes per donor were collected
      from group MV (15.2 +/- 5.5) than from group MF (9.0 +/- 3.2). An absolute
      maturational failure was observed in oocytes collected from groups SF2 and SF3.
      Maturational competence varied between 16.7% and 58.3% (p = 0.017) among sessions
      of group MF, but it was more uniform among sessions of group MV (range 12.5
      42.9%, p > 0.05). Our results indicate that firstly, the number and the quality
      of harvested oocytes from juvenile lambs can be much improved if follicular
      stimulation regime is adjusted to the body weight. Secondly, in terms of
      follicular population and oocyte quality, 3 and 4-month-old lambs are naturally
      bad oocyte donors, but this characteristic can be reversed by a previous
      follicular ablation.

PMID- 17506800
TI  - Measurement of faecal progesterone metabolites and its application for early
      screening of open cows post-insemination.
AB  - The present study investigated the changes of serum progesterone (P4) and its
      faecal metabolites in pregnant and non-pregnant cows (Expt 1) and the feasibilty
      of using faecal P4 metabolites for early screening of open cows post-insemination
      (Expt 2). In Expt 1, seven crossbred Holstein-Friesian (HF) cows were studied.
      Serum and faecal samples were collected once daily from the day of artificial
      insemination (AI) until 25 days after AI. In Expt 2, 27 crossbred HF inseminated
      cows were employed. Serum and faecal samples were obtained on the day of AI (day
      0) and on days 19-22 post-insemination. Enzyme immunoassay measurements of serum
      P4 and faecal P4 metabolites were established. The low detection limit of the
      assay was 0.01 ng/ml and the amount of P4, resulting in a 50% reduction in the
      initial binding value, was 1.07 ng/ml. The intra- and inter-assay coefficients of
      variation were <8% and <14%, respectively. A positive correlation between the
      levels of serum P4 and faecal P4 metabolites was found in every single cow (r =
      0.73-0.88, p < 0.001) and pooled data (r = 0.78, p < 0.001). The estimated value
      of faecal P4 metabolites at 100 ng/g of faeces was equal to the serum P4 levels
      of 1 ng/ml. The accuracies of pregnancy and non-pregnancy diagnosis based on the
      analyses of faecal P4 metabolites between day 0 and days 19-22 post-insemination,
      were 67% and 100%, respectively. In conclusion, the measurement of faecal P4
      metabolites can be a potentially alternative method for early screening of open
      cows post-insemination with the same accuracy and precision, as measured by serum
      P4 assay.

PMID- 17506801
TI  - Heterospecific nuclear-transferred embryos derived from equine fibroblast cells
      and enucleated bovine oocytes.
AB  - This study was conducted to reconstruct heterogeneous embryos using equine skin
      fibroblast cells as donor karyoplasts and the bovine oocytes as recipient
      cytoplast for investigating the reprogramming of equine somatic cell nuclear in
      bovine oocyte cytoplasm and the developmental potential of the reconstructed
      embryos. Adult horse skin fibroblast cells serum-starved were used as donor
      somatic cells. Bovine oocytes matured in vitro were employed as recipient
      cytoplasts. The fusion of fibroblast cells into recipient cytoplasm was induced
      by electofusion. The fused eggs were activated by inomycin with 2 mm/ml 6
      dimethylaminopurine (6-DMAP). The activated reconstructed embryos were co
      cultured with bovine cumulus cells in synthetic oviduct fluid supplemented with
      amino acid (SOFaa) and 10% fetal calf serum (FCS) for 168 h. The results showed
      that the first completed cleavage of xenonuclear transfer equine embryos occurred
      between 30 and 48 h following activation. 52% of the injected oocytes were
      successfully fused, 72% of the fused eggs underwent the first egg cleavage and
      17% of the heterospecific nuclear-transferred zygotes developed to 4- or 8-cell
      embryo stages. This study demonstrated that the reconstructed embryos have
      undergone the first embryonic division and the reprogramming of equine fibroblast
      nuclei can be initiated in bovine-enucleated oocytes.

PMID- 17506802
TI  - Vitamin E biochemistry and function: a case study in male rabbit.
AB  - Vitamin E supplementation has become a common procedure to promote growth and
      health and improve the qualitative characteristics of farm animals. It has been
      demonstrated to be an efficient strategy for improving their reproductive
      function. Germ cells are particularly vulnerable to oxidative damage and may thus
      require additional antioxidant protection. The aim of this review is to give a
      comprehensive overview of the current knowledge of the biochemistry and
      physiology of vitamin E; successively, the effect of this compound on the
      reproductive activity of rabbit buck is accurately described. In particular, this
      review examines studies on the effects of animal age, dose and duration of
      vitamin E supplementation, as well as the co-supplementation with selenium,
      vitamin C and polyunsaturated fatty acids. Several investigations have shown
      beneficial effects in bucks supplemented with vitamin E levels higher than the
      standard dietary requirement (50 mg/kg) particularly when the semen is stored.
      However, the exact dietary intake of vitamin E should be decided according to
      specific tissue needs for the individual vitamin E forms and the specific
      saturation markers.

PMID- 17506803
TI  - Measurement of ovine pregnancy-associated glycoprotein (PAG) during early
      pregnancy in Lacaune sheep.
AB  - This study describes ovine pregnancy-associated glycoprotein (ovPAG)
      concentrations in 20 Lacaune sheep during early pregnancy. Measurements were
      performed by using semi-purified ovPAG as standard, tracer and immunogens for
      antibody production in rabbits. Antisera R780 (against ovPAG(57+59kDa)) and R805
      (against ovPAG5(58+61kDa)) were used respectively in RIA-780 and RIA-805. Blood
      samples were collected at days 0, 18, 20, 22 and 25 after artificial
      insemination. From day 18 after breeding onward, the mean ovPAG concentration was
      significantly higher (p < 0.001) in plasma samples from pregnant ewes (n = 17)
      than in non-pregnant ones (n = 3). The specific activity of the tracer was 11 760
      Ci/mmol in RIA-780 and 14 900 Ci/mmol in RIA-805. The minimal detection limits
      for RIA-780 and RIA-805 were 0.2 ng/ml and 0.3 ng/ml, respectively. The intra
      assay CV of samples with low (1.0 ng/ml), medium (2.5 ng/ml) and high (4.0 ng/ml)
      PAG concentrations were 3%, 6% and 9% for RIA-780 and 8%, 9% and 5% for RIA-805.
      The inter-assay CV in the same samples were 13%, 12% and 7% for RIA-780 and 13%,
      11% and 5% for RIA-805. The recovery was higher than 95% in both assays. No cross
      reaction was observed with members of aspartic proteinase family as well as with
      other tested proteins. In both RIA-780 and RIA-805, inhibition of the binding of
      the tracer by antisera was parallel between standard curve and serial dilutions
      of pregnant ewe samples. In conclusion, the two homologous RIA systems are
      suitable for early quantification of ovPAG concentrations in ewe plasma samples
      from day 18 after breeding.

PMID- 17506804
TI  - Quality and developmental ability of dromedary (Camelus dromedarius) embryos
      obtained by IVM/IVF, in vivo matured/IVF or in vivo matured/fertilized oocytes.
AB  - The effect of source of cumulus-oocytes-complexes (COCs), maturation and
      fertilization conditions on developmental competence of dromedary embryos was
      examined. Thirty-six adult females were superovulated with equine Chorionic
      Gonadotropin (eCG) injection (3500 IU, IM) and divided in three groups of 12
      females each. Group 1 provided 138 COC's collected from follicles >or= 5 mm 10
      days after stimulation prior hCG treatment and matured in vitro for 30 h. Group 2
      provided 120 in vivo matured oocytes which were aspirated from their follicles 20
      h after hCG (3000 IU, IV) given on day 10 follow eCG injection. Group 3 provided
      65 in vivo matured/fertilized oocytes. Females in Group 3 received hCG on day 10
      following eCG treatment and then were mated 24 h later. Fertilized oocytes were
      collected from the oviducts of females 48-h post-mating. Quality of the oocytes
      was assessed after in vitro maturation (IVM), in vitro fertilization (IVF) and in
      vitro culture (IVC) of COCs. All cultures were performed in three replicates (n =
      3) at 38.5 degrees C, under 5% CO(2) and high humidity (>95%). Only COCs with
      cumulus and homogenous (dark) cytoplasm were used. Nuclear maturation rate for
      Groups 1 and 2 was determined by epifluorescence microscopy in a sample of COCs
      (n = 30) denuded, fixed and stained with Hoechst 33342. To study the viability of
      obtained embryos, hatched blastocysts from each group were transferred to
      recipients followed by pregnancy diagnosis using ultrasonography at 15, 60 and 90
      days. The percentage of COCs reaching metaphase II (MII) after 30 h of maturation
      was slightly but not significantly higher for in vivo matured oocytes (28/30;
      93%) than those in vitro matured (25/30; 84%). The total rate of cleavage (2
      cells to blastocyst stage) was not different for the three groups. However,
      significantly (p < 0.05) more blastocyst and hatched blastocysts were obtained
      from in vivo matured and in vivo fertilized oocytes (Group 3; 52% and 73%) than
      from in vitro fertilized oocytes whether they were matured in vitro (Group 1; 35%
      and 32%) or in vivo (Group 2; 32% and 45%). Pregnancy rates were not
      significantly different amongst all groups for the three first months following
      embryo transfer. All pregnancies were lost after day 90 follow transfer except
      for in vivo matured and in vivo matured/fertilized groups. Only in vivo
      matured/in vitro fertilized and in vivo matured/fertilized produced embryos
      continued normal development until term and resulted in the birth of normal and
      healthy live calves. Six claves (29%; 6/21) were born from Group 3 and one (8%;
      1/13) calf was born from Group 2. This study shows that the IVC system used is
      able to support camel embryo development. However, developmental competence and
      viability of dromedary embryos may be directly related to the intrinsic quality
      (cytoplasmic maturation) of oocytes.

PMID- 17506805
TI  - Effects of increased ambient temperature during IVM and/or IVF on the in vitro
      development of bovine zygotes.
AB  - Previous research by this group (2003) has demonstrated that heat stress during
      in vitro culture (IVC) significantly increased early embryo mortality. The
      experiments reported here examine the effects of heat treatment (HT) during in
      vitro maturation (IVM) and during in vitro fertilization (IVF). One 24 h cycle of
      HT entailed a series of 0.5 degrees C incubator temperature increases from 39
      degrees C to 39.5 degrees C for 2 h, to 40 degrees C for 2 h, to 40.5 degrees C
      for 4 h, 41 degrees C for 4 h, 40.5 degrees C for 6 h and 40 degrees C for 6 h.
      This cycle mimics rectal temperatures recorded in high producing, grain fed dairy
      cows in hot climates. Experiment I studied the effects of one cycle of heat
      treatment during IVF on the rate of cleavage of in vitro matured presumptive
      zygotes. Total cleavage rate in the HT group (37.8%) was lower than that of the
      control group (54.6%, p < 0.05). Experiment II repeated the HT of experiment I
      but preceded it with a cycle of HT during IVM. The total cleavage rates for
      control and heat treatment groups were 75.5% and 37.9%, respectively, with a
      significant difference of p < 0.001 identified. Experiment III examined the rates
      of embryonic development to >or=8-cell stage (after 72 h IVC) and to morula or
      blastocyst (M/B) stage (after 144 h IVC) following HT of the oocyte groups during
      the preceding IVM or IVF. Rates of development to >or=8-cell stage (at 72 h IVC)
      and to M/B stage (after 144 h IVC) for the control group were 27.5% and 35.8%.
      Those of IVM-only HT and IVF-only HT groups were 13.8% and 14.6%, and 8.6% and
      14.3%, respectively. Both groups of heat treated embryos developed at
      significantly lower rates (p < 0.05) than did the control group. These results
      suggest that hyperthermia during oocyte maturation and/or fertilization adversely
      affects oocyte maturation and fertilization rates and retards further embryonic
      development.

PMID- 17506806
TI  - Post-mortem examination of sows genital organs culled for reproductive
      disturbances and immunohistochemical studies on ERalpha and PR A receptors in the
      anoestral sows uterus.
AB  - The aim of present study was post-mortem examination of ovaries, uterus and
      plasma oestradiol-17beta (E2) and progesterone (P4) concentrations in the blood
      of sows with reproductive disturbances and the distribution of oestradiol
      receptor (ERalpha), as well as progesterone (PR-A) in the anoestrous sows uteri.
      Reproductive organs of 150 crossbred sows (Lithuanian White x Danish Landrace)
      culled for the reasons of reproductive disturbances, were collected in local
      abattoir over a period of 3 months (September-November). Organs were assessed to
      determine the stage of the oestrous cycle or anoestrus and their development.
      Blood samples were collected for E2 and P4 analysis from the jugular vein 1 h
      prior to slaughter. For this study uterine samples only from pathological
      anoestrous sows were subjected to immunohistochemical staining to assess the
      distribution of ERalpha and PR-A in surface epithelium, subepithelial connective
      tissue, glandular epithelium and myometrium. Macroscopic examination of the
      ovaries showed that 68.7% sows had active cycling ovaries, 26.6% sows were
      anoestrus, ovaries were small without CL, and 4.7% of sows had multiple
      follicular cysts. In anoestrous sows (n = 27) the number and intensity of the
      nuclear staining of ERalpha varied between different uterine tissue compartments.
      The highest number (>80%) and the strongest intensity (+++) of positively stained
      cells for ERalpha was seen in myometrium and glandular epithelium. In other
      uterine wall compartments the number and intensity of positively stained for
      ERalpha nuclei was lower (+/++). The PR-A was absent from all tissue
      compartments. The intensity of the nuclear staining for ERalpha varied not only
      between the different uterine compartments but also between the sows. The 11.1%
      of the sows presented ERalpha in surface epithelium, 74.1% of the sows in
      glandular epithelium and 63.0% of sows in the myometrium.

PMID- 17506807
TI  - Sperm morphology in the domestic cat, and its relation with fertility: a
      retrospective study.
AB  - Knowledge about normal ranges in semen quality and the association between sperm
      morphology and fertility in felids is limited. The aims of this retrospective
      study were to (1) define a normal spermiogram in cats; (2) evaluate possible
      effects of season, age and breed on sperm morphology; and (3) evaluate the
      relationship between sperm morphology and fertility. Semen samples collected by
      electroejaculation from 52 cats were evaluated for sperm morphology. The cats
      constituted two groups: a general population of cats (n = 48) and cats examined
      because of poor breeding records (n = 4). The general population was divided into
      household (n = 20), pedigree (n = 19) and colony cats (n = 9) and into three age
      classes, <12 months, 12-59 months and >or=60 months. The median percentage of
      normal spermatozoa in the general population was 44.0% (range 1.0-91.0%).
      Criteria were tentatively set for what was considered a normal spermiogram. The
      mean percentage of normal spermatozoa was higher during February to July than
      during August to January (p < 0.05). Pedigree cats had a lower mean percentage of
      normal spermatozoa than did household cats (p < 0.05). Age had no effect on the
      percentage of normal spermatozoa but was positively correlated with the
      percentage of proximal droplets. Of the cats with <40% normal spermatozoa (n =
      19), all those with known breeding records (n = 11) had produced litters. The
      four cats examined because of poor breeding results had higher percentages of
      different sperm abnormalities than tentatively stipulated for the normal
      spermiogram. In two of these cats both sperm morphology and fertility changed
      over time.

PMID- 17506808
TI  - Regional and cyclic variations in the ultrastructural features of secretory cells
      in the oviductal epithelium of the Chinese Meishan pig.
AB  - The Chinese Meishan pig is prolific breed and it is considered that this pig has
      a capacity with higher rates of embryonic survival. The oviductal secretory cells
      may affect the embryonic development and survival. The aim of the present study
      was to investigate the ultrastructural features of secretory cells in the various
      regions of the Chinese Meishan pig oviduct during the follicular and luteal
      phases of the oestrous cycle. In the ampullar secretory cells, numerous secretory
      granules with moderately electron-dense matrices were present in the supranuclear
      cytoplasm and exocytosis of secretory granules was observed. The number of
      secretory granules was dramatically reduced in the ampullar secretory cells in
      the luteal phase. During the follicular phase in the fimbrial epithelium, the
      secretory cells contained rough endoplasmic reticulum and Golgi apparatus, but
      most cells had few small granules. In the luteal phase, the secretory cells in
      the ampullar and fimbrial epithelia extended beyond the luminal border of the
      ciliated cells. In the isthmus, many granules were present in the cytoplasm of
      secretory cells throughout the oestrous cycle, but the number of secretory
      granules was reduced in the luteal phase. The cytomorphometric data revealed that
      the height of ciliated cells decreased substantially in the fimbriae and ampulla
      at the luteal phase, while that of non-ciliated cells was less affected. These
      results suggest that the drastic reduction of cell height of ciliated cells cause
      the extrusion of most secretory cells beyond the ciliated cells in the fimbriae
      and ampulla during the luteal phase. In summary, our ultrastructural observations
      of Chinese Meishan pig oviduct revealed marked cyclic changes in the
      ultrastructural features of secretory cells. In particular, the ultrastructural
      features and the numbers of secretory granules were distinctive for each
      particular segment. These findings should provide insight into the regional and
      cellular differences in functions of secretory cells of the Chinese Meishan pig
      oviduct.

PMID- 17506809
TI  - A low oxygen atmosphere during IVF accelerates the kinetic of formation of in
      vitro produced ovine blastocysts.
AB  - Among the factors that affect in vitro embryo development, oxygen atmosphere is
      considered to be of great influence. In this study, we evaluated the influence of
      two different oxygen atmospheres during in vitro fertilization (IVF) of ovine
      oocytes on their developmental capacity and quality assessed by cryotolerance.
      Cumulus oocyte complexes derived from ovaries of slaughtered sheep were matured
      in vitro and subsequently fertilized under low (5%) or high (20%) oxygen
      atmospheres, and cultured in SOF + aa + 0.4% BSA in 5% CO2 and 5% O2 up to
      blastocyst stage. The cleavage rates obtained in the fertilization system at 20%
      O2 were significantly higher than those obtained in the 5% O2 fertilization
      system (61.2% vs 50.8%; p < 0.01). The distribution of cleaved oocytes at 22, 26
      and 40 h of culture intervals was not different in the low or high O2 atmosphere
      (31.4%, 26.4% and 42.1% vs 28.0%, 29.3% and 42.7% respectively). Blastocysts
      output on the 6th day post-fertilization (dpf) was significantly higher when
      oocytes were fertilized under 5% O2 concentration (63.04% in 5% O2 vs 47.36% in
      20% O2), while on the 7th dpf the higher number of blastocysts was obtained in
      the 20% O2 system (35.10%.in 20% O2 vs 26.09% in 5% O2). After vitrification no
      differences were observed between low or high oxygen atmosphere in the viability
      rates of blastocysts obtained on day 6 (93.6% vs 96.5%), on day 7 (46.3% vs
      41.7%) and on day 8 (11.1% vs 6.6%). After differential staining, no significant
      differences were observed in the total cell number and inner cell mass and
      trophoblastic cells ratio of blastocysts produced on 6 dpf (189.6 +/- 51.3 and
      0.260 +/- 0.07 vs 223.3 +/- 45.6 and 0.277 +/- 0.09), on 7 dpf (168.3 +/- 25.1
      and 0.316 +/- 0.06 vs 172.1 +/- 33,6 and 0.320 +/- 0.06) and on 8 dpf (121.2 +/-
      23,8 and 0.302 +/- 0.03 vs 117.0 +/- 35.1 and 0.313 +/- 0.04) under low or high
      oxygen atmosphere respectively). In conclusion, our data suggest that low oxygen
      atmosphere during IVF affects positively the production of high quality ovine
      blastocysts.

PMID- 17506810
TI  - Post-thaw survival and longevity of bull spermatozoa frozen with an egg yolk
      based or two egg yolk-free extenders after an equilibration period of 18 h.
AB  - The aim of the present study was to determine the suitability of using two egg
      yolk-free commercial extenders, Andromed and Biociphos Plus as compared with the
      Tris-egg yolk based diluent Biladyl, for the cryopreservation of bull spermatozoa
      when the freezing protocol involved holding the extended semen at 4 degrees C for
      18 h before the freezing. Six ejaculates from each of 10 Holstein bulls were
      collected by using artificial vagina. The ejaculates were evaluated for volume,
      sperm concentration and motility, divided in to three equal volumes, and diluted,
      respectively, with the three extenders as specified above. Extended semen was
      equilibrated for 18 h at 4 degrees C and frozen in 0.25-ml straws. After thawing,
      100-mul aliquots of semen were labelled with SYBR-14, PI and PE-PNA
      (Phycoerythrin-conjugated Peanut agglutinin) and analysed by flow cytometry at 0,
      3, 6 and 9 h after incubation at 37 degrees C. A General Lineal Model procedure
      for repeated measures was used to determine the effects of extender, bull,
      replicate and the interaction between them, on sperm viability and acrosomal
      integrity. Semen samples frozen with Biladyl showed higher (p < 0.001) sperm
      survival after 0 h (47.9%) and 9 h (30.3%) of incubation than those frozen with
      Andromed (38.5% and 17.3%, after 0 and 9 h respectively) or Biociphos Plus (34.9%
      and 21.6%, after 0 and 9 h respectively). The bull and replicate had significant
      effects (p < 0.001) on both sperm viability and acrosomal integrity, but the
      interactions between bull and extender and between replicate and extender were
      not significant. It was concluded that, when holding the semen overnight before
      freezing, the use of Biladyl results in higher sperm survival and longevity than
      the use of Andromed or Biociphos Plus.

PMID- 17506811
TI  - Multivariate cluster analysis regression procedures as tools to identify motile
      sperm subpopulations in rabbit semen and to predict semen fertility and litter
      size.
AB  - Computerized motility analysis (CASA) shows that four separate subpopulations of
      spermatozoa with different motility characteristics co-exist in rabbit
      ejaculates. There were significant (p < 0.01) differences in the distribution of
      these subpopulations among separate genetic lines, total sperm abnormalities and
      the percentage of altered acrosomes. Furthermore, logistic and linear
      multivariate regressions among several parameters of rabbit semen quality
      analysis were tested for use as predictive tools for the fertilizing ability of a
      specific artificial insemination semen sample. Logistic regression analysis
      rendered two mathematical, significant (p < 0.01) models: one between sperm
      viability and conception rate and the other between total sperm abnormalities and
      conception rate. Multiple linear regression analyses also yielded some
      significant relationships between both fertility (p < 0.001) and litter size (p <
      0.05), with respect to some semen characteristics. Our results support the
      hypothesis that the predictive in vivo fertility use of the standard rabbit semen
      quality analysis coupled with a CASA determination could be reasonably achieved
      by applying linear and logistic regression analyses among several parameters of
      rabbit semen quality analysis.

PMID- 17506812
TI  - Effect of progesterone and oestradiol on sperm-zona binding and acrosome reaction
      in bovine spermatozoa after thawing.
AB  - This study was conducted assess spermatozoa binding capacity to the oocyte in the
      presence of 0.1 or 0.5 microg/ml progesterone (P4) or a combination of 0.5
      microg/ml P4 with 0.1 microg/ml oestradiol (OE). The number of oocyte-bound
      spermatozoa in the presence of progesterone was significantly higher (p < 0.05 to
      p < 0.001) when compared with the control samples, that were incubated in the
      absence of P4. Spermatozoa binding to the zona pellucida (ZP) of the oocyte were
      concentration-dependent - significantly higher numbers of spermatozoa were bound
      in the presence of 0.5 microg/ml P4, when compared with that of 0.1 microg/ml P4.
      Oestradiol at 0.1 microg/ml concentration used impaired the effect of
      progesterone-mediated sperm-oocyte binding. The incidences of acrosome-reacted
      (AR) spermatozoa bound to the ZP - following 0, 60, 120 and 180 min. incubation
      in the presence and absence of 1 microg/ml progesterone was also assessed. Only
      at 180 min of incubation a higher (p < 0.001) incidence of the AR-spermatozoa was
      found in sperm-ZP complexes incubated in the presence or absence of progesterone,
      being 56.5 +/- 11.1 and 43.2 +/- 8.8 % respectively. In conclusion, progesterone
      enhances the sperm-ZP binding capacity. Progesterone affects the incidences of AR
      on zona-bound spermatozoa only after prolonged co-culture.

PMID- 17506813
TI  - Genetic parameters for semen production traits in Austrian dual-purpose Simmental
      bulls.
AB  - Genetic parameters were estimated for semen production traits collected in an
      Austrian AI centre in the years 2000-2004. In total, 12,746 ejaculates from 301
      Austrian dual-purpose Simmental (Fleckvieh) AI bulls were examined considering
      different effects on ejaculate volume, sperm concentration, percentage of viable
      spermatozoa in the ejaculate, total spermatozoa per ejaculate and motility. The
      model for genetic parameter estimation included the fixed effects age of bull,
      collection interval, number of collections on collection day, bull handler, semen
      collector, year and month of collection, a random additive genetic component and
      a permanent environmental effect. Correlations between estimated breeding values
      for semen traits and male fertility from the routine evaluation were calculated.
      The fertility trait considered in the routine evaluation is non-return rate 90
      for the first insemination. All semen production traits were moderately
      heritable. Heritabilities for volume, concentration, percentage of viable
      spermatozoa, total number of spermatozoa and motility were 0.18, 0.14, 0.10, 0.22
      and 0.04, respectively. Correlations between breeding values for semen quality
      traits and routinely estimated breeding values for male fertility were low and
      ranged from 0.08 to 0.17 indicating that semen production traits are rather poor
      predictors of male fertility.

PMID- 17506814
TI  - Follicle development during luteal phase and altrenogest treatment in pigs.
AB  - Synchronization of the oestrous cycle of gilts using altrenogest treatment has
      been found to increase ovulation rate. The current experiment investigated if the
      increase in ovulation rate after altrenogest treatment is related to increased
      follicle size at the end of altrenogest treatment compared with late luteal phase
      follicles. Crossbred gilts (n = 15) received altrenogest during 18 days [20 mg
      Regumate (Janssen Animal Health, Beerse, Belgium)], starting 5-7 days after onset
      of first oestrus. Control gilts (n = 15) did not receive altrenogest. At days 10
      12 of the oestrous cycle [i.e. in the presence of corpora lutea (CL)], average
      follicle development was 2.51 +/- 0.20 mm (assessed with ultrasound) in
      altrenogest-treated gilts and 2.58 +/- 0.16 mm in control gilts (p > 0.10).
      During the last days of altrenogest treatment (i.e. when CL had gone into
      regression), average follicle size had increased to 3.01 +/- 0.31 mm (p < 0.05).
      Subsequent ovulation rate was 16.6 +/- 1.7 in altrenogest treated gilts and 15.1
      +/- 1.2 in control gilts (p < 0.05). Altrenogest treatment resulted in increased
      follicle size after regression of the CL, showing that suppression of follicle
      growth by altrenogest alone is less severe than suppression by endogenous
      progesterone (either with or without altrenogest). Altrenogest treatment also
      resulted in a higher ovulation rate. However, it is unclear if the increased
      follicle size and higher ovulation rate after altrenogest treatment are causally
      related, as the relation between the two on an animal level was not significant.

PMID- 17506815
TI  - Embryonic loss in sows with repeated propensity for small litter size.
AB  - Information is lacking as to the timing and cause of sows that repeatedly have
      low litter size over several parities. Sows evaluated for the present study had
      at least two parities either small <or=7 (SL) or normal >or=12 (NL) litter size.
      Following breeding of sows with contemporary boars, reproductive tracts were
      obtained on day 30 of gestation. There was no difference (p > 0.10) between SL
      and NL sows in the number of CL, embryo weight or placental length. The total
      number of embryos and embryonic survival tended to be lower (p < 0.10) in SL sows
      compared with NL sows, but there were 5.1 less viable embryos (p < 0.03) in SL.
      Results indicate that time of conceptus loss in SL sows was variable throughout
      gestation.

PMID- 17506816
TI  - Restriction of Legionella pneumophila growth in macrophages requires the
      concerted action of cytokine and Naip5/Ipaf signalling pathways.
AB  - Macrophages from the C57BL/6 (B6) mouse strain restrict intracellular growth of
      Legionella pneumophila, whereas A/J macrophages are highly permissive. The
      mechanism by which B6 macrophages restrict Legionella growth remains poorly
      understood, but is known to require the cytosolic microbe sensors Naip5 (Birc1e)
      and Ipaf. We hypothesized that Naip5 and Ipaf may act in partnership with other
      antimicrobial signalling pathways in macrophages. Indeed, we found that
      macrophages lacking either tumour necrosis factor (TNF)-alpha or type I
      interferon (IFN) signalling are permissive for growth of L. pneumophila, even in
      the presence of functional Naip5 and Ipaf alleles. Similarly, macrophages lacking
      Naip5 and/or Ipaf signalling were permissive even though we found that Naip5 or
      Ipaf were not required for induction of TNF-alpha and type I IFN. Therefore, our
      data suggest that the mechanism by which B6 macrophages restrict intracellular
      replication of L. pneumophila is more complex than previously appreciated, and
      involves the concerted action of cytokine and intracellular microbe sensor
      signalling pathways.

PMID- 17506817
TI  - Should I stay or should I go? Nucleocytoplasmic trafficking in plant innate
      immunity.
AB  - Communication between the cytoplasm and the nucleus is a fundamental feature of
      eukaryotic cells. Bidirectional transport of macromolecules across the nuclear
      envelope is typically mediated by receptors and occurs exclusively through
      nuclear pore complexes (NPCs). The components and molecular mechanisms regulating
      nucleocytoplasmic trafficking and signalling processes are well studied in
      animals and yeast but are poorly understood in plants. Current work shows that
      components of the NPC and the nuclear import and export machinery play essential
      roles in plant innate immunity. Translocation of defence regulators and
      Resistance (R) proteins between the cytoplasm and the nucleus are recently
      uncovered aspects of plant defence responses against pathogens. Future studies
      will reveal more details on the spatial and temporal dynamics and regulation of
      this process.

PMID- 17506818
TI  - Innate immunity to respiratory viruses.
AB  - Pattern recognition receptors are critically involved in the development of
      innate and adaptive antiviral immunity. Innate immune activation by viruses may
      occur via cell surface, intracellular and cytosolic pattern recognition
      receptors. These receptors sense viral components and may activate unique
      downstream pathways to generate antiviral immunity. In this article, we summarize
      the pattern recognition receptors that recognize major human respiratory viral
      pathogens, including influenza virus, respiratory syncytial virus and adenovirus.
      We also provide an overview of the current knowledge of regulation of type I
      interferons and inflammatory cytokines in viral infection.

PMID- 17506819
TI  - An NSP4-dependant mechanism by which rotavirus impairs lactase enzymatic activity
      in brush border of human enterocyte-like Caco-2 cells.
AB  - Lactase-phlorizin hydrolase (LPH, EC 3.2.1.23-62) is a brush border membrane
      (BBM)-associated enzyme in intestinal cells that hydrolyse lactose, the most
      important sugar in milk. Impairing in lactase activity during rotavirus infection
      has been described in diseased infants but the mechanism by which the functional
      lesion occurs remains unknown. We undertook a study to elucidate whether
      rotavirus impairs the lactase enzymatic activity in BBM of human enterocyte
      cells. In this study we use cultured human intestinal fully differentiated
      enterocyte-like Caco-2 cells to demonstrate how the lactase enzymatic activity at
      BBM is significantly decreased in rhesus monkey rotavirus (RRV)-infected cells.
      We found that the decrease in enzyme activity is not dependent of the Ca(2+)- and
      cAMP-dependent signalling events triggered by the virus. The LPH biosynthesis,
      stability, and expression of the protein at the BBM of infected cells were not
      modified. We provide evidence that in RRV-infected cells the kinetic of lactase
      enzymatic activity present at the BBM was modified. Both BBM(control) and
      BBM(RRV) have identical K(m) values, but hydrolyse the substrate at different
      rates. Thus, the BBM(RRV) exhibits almost a 1.5-fold decreased V(max) than that
      of BBM(control) and is therefore enzymatically less active than the latter. Our
      study demonstrate conclusively that the impairment of lactase enzymatic activity
      at the BBM of the enterocyte-like Caco-2 cells observed during rotavirus
      infection results from an inhibitory action of the secreted non-structural
      rotavirus protein NSP4.

PMID- 17506820
TI  - The specific innate immune receptor CEACAM3 triggers neutrophil bactericidal
      activities via a Syk kinase-dependent pathway.
AB  - The human-restricted pathogens Neisseria gonorrhoeae, Neisseria meningitidis,
      Haemophilus influenzae and Moraxella catarrhalis colonize host tissues via
      carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). One such
      receptor, CEACAM3, acts in a host-protective manner by orchestrating the capture
      and engulfment of invasive bacteria by human neutrophils. Herein, we show that
      bacterial binding to CEACAM3 causes recruitment of the cytoplasmic tyrosine
      kinase Syk, resulting in the phosphorylation of both CEACAM3 and Syk. This
      interaction is specific for the immunoreceptor tyrosine-based activation motif
      (ITAM) in the CEACAM3 cytoplasmic domain. While dispensable for the phagocytic
      uptake of single bacteria by CEACAM3, Syk is necessary for internalization when
      cargo size increases or when the density of CEACAM-binding ligand on the cargo
      surface is below a critical threshold. Moreover, Syk engagement is required for
      an effective bacterial killing response, including the neutrophil oxidative burst
      and degranulation functions in response to N. gonorrhoeae. These data reveal
      CEACAM3 as a specific innate immune receptor that mediates the opsonin
      independent clearance of CEACAM-binding bacteria via Syk, a molecular trigger for
      functional immunoreceptor responses of both the adaptive (TCR, BCR, FcR) and
      innate (Dectin-1, CEACAM3) immune systems.

PMID- 17506821
TI  - Arrested maturation of Neisseria-containing phagosomes in the absence of the
      lysosome-associated membrane proteins, LAMP-1 and LAMP-2.
AB  - Mature, microbicidal phagosomes are rich in the lysosome-associated membrane
      proteins, LAMP-1 and LAMP-2, two highly glycosylated proteins presumed to form a
      protective barrier lining the phagosomal membrane. Pathogenic Neisseria secrete a
      protease that selectively cleaves LAMP-1, suggesting a critical role for LAMP
      proteins in the microbicidal competence of phagosomes. To determine the
      requirement for LAMP proteins in bacterial phagocytosis, we employed embryonic
      fibroblasts isolated from knockout mice lacking lamp-1, lamp-2 or both genes, as
      well as small interfering RNA (siRNA)-mediated knockdown of LAMP expression in a
      human epithelial cell line. Like wild-type cells, those lacking either LAMP-1 or
      LAMP-2 alone formed phagosomes that gradually acquired microbicidal activity and
      curtailed bacterial growth. In contrast, LAMP-1 and LAMP-2 double-deficient
      fibroblasts failed to kill engulfed Neisseria gonorrhoeae. In these cells,
      maturation was arrested prior to the acquisition of Rab7. As a result, the Rab7
      interacting lysosomal protein (RILP, a Rab7 effector) was not recruited to the
      phagosomes, which were consequently unable to undergo dynein/dynactin-mediated
      centripetal displacement along microtubules and remained in a predominantly
      peripheral location. The inability of such phagosomes to migrate towards
      lysosomes likely contributed to their incomplete maturation and inability to
      eliminate bacteria. These findings suggest that neisserial degradation of LAMP-1
      is not sufficient to affect its survival within the phagosome, and establish LAMP
      proteins as critical components in the process whereby phagosomes acquire
      microbicidal capabilities.

PMID- 17506822
TI  - Naturally occurring single and double infection with Wolbachia strains in the
      butterfly Eurema hecabe: transmission efficiencies and population density
      dynamics of each Wolbachia strain.
AB  - Wolbachia belonging to Alphaproteobacteria are transovarially transmitted
      bacteria responsible for reproductive alterations in a wide range of arthropods.
      In natural populations of the butterfly Eurema hecabe, there are two different
      types of Wolbachia-infected individuals. Individuals singly infected with
      Wolbachia strain wHecCI exhibit strong cytoplasmic incompatibility, whereas those
      doubly infected with wHecCI and wHecFem exhibit feminization. Here, we examined
      the infection frequencies and population densities of each Wolbachia strain in
      different host tissues (ovary, testis, fat body, midgut, Malpighian tubule and
      leg), and the cost of infection in offspring produced by single-infected and
      double-infected mothers of E. hecabe. The vertical transmission rate of wHecCI
      was nearly 100%, and that of wHecFem was c. 80%. The wHecCI densities were 10(3)
      10(4)-fold higher than the wHecFem densities. In most tissues, the wHecCI
      densities were significantly higher in offspring of single-infected mothers than
      in offspring of double-infected mothers. In offspring of double-infected mothers,
      however, the wHecCI densities were not affected by the presence of wHecFem,
      suggesting a lack of interaction between the wHecCI and wHecFem densities. The
      offspring development time was dependent on the infection status of the mothers.
      These results imply that the maternal infection status affects the Wolbachia
      densities and fitness of offspring.

PMID- 17506824
TI  - Bacterial symbionts in the hepatopancreas of isopods: diversity and environmental
      transmission.
AB  - The midgut glands (hepatopancreas) of terrestrial isopods contain bacterial
      symbionts. We analysed the phylogenetic diversity of hepatopancreatic bacteria in
      isopod species from various suborders colonizing marine, semiterrestrial,
      terrestrial and freshwater habitats. Hepatopancreatic bacteria were absent in the
      marine isopod Idotea balthica (Valvifera). The symbiotic bacteria present in the
      midgut glands of the freshwater isopod Asellus aquaticus (Asellota) were closely
      related to members of the proteobacterial genera Rhodobacter, Burkholderia,
      Aeromonas or Rickettsiella, but differed markedly between populations. By
      contrast, species of the suborder Oniscidea were consistently colonized by the
      same phylotypes of hepatopancreatic bacteria. While symbionts in the
      semiterrestrial isopod Ligia oceanica (Oniscidea) were close relatives of
      Pseudomonas sp. (Gammaproteobacteria), individuals of the terrestrial isopod
      Oniscus asellus (Oniscidea) harboured either 'Candidatus Hepatoplasma
      crinochetorum' (Mollicutes) or 'Candidatus Hepatincola porcellionum'
      (Rickettsiales), previously described as symbionts of another terrestrial isopod,
      Porcellio scaber. These two uncultivated bacterial taxa were consistently present
      in each population of six and three different species of terrestrial isopods,
      respectively, collected in different geographical locations. However, infection
      rates of individuals within a population ranged between 10% and 100%, rendering
      vertical transmission unlikely. Rather, feeding experiments suggest that
      'Candidatus Hepatoplasma crinochetorum' is environmentally transmitted to the
      progeny.

PMID- 17506823
TI  - Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria:
      producer phenotyping and relation with intestinal community.
AB  - Many studies have investigated the importance of the intestinal bacterial
      activation of individual phytoestrogens. However, human nutrition contains
      different phytoestrogens and the final exposure depends on the microbial
      potential to activate all different groups within each individual. In this work,
      interindividual variations in the bacterial activation of the different
      phytoestrogens were assessed. Incubation of feces from 100 individuals using
      SoyLife EXTRA, LinumLife EXTRA and isoxanthohumol suggested that individuals
      could be separated into high, moderate and low O-desmethylangolensin (O-DMA),
      equol, enterodiol (END), enterolactone (ENL) or 8-prenylnaringenin producers, but
      that the metabolism of isoflavones, lignans and prenylflavonoids follows
      separate, independent pathways. However, O-DMA and equol production correlated
      negatively, whereas a positive correlation was found between END and ENL
      production. In addition, END production correlated negatively with Clostridium
      coccoides-Eubacterium rectale counts. Furthermore, O-DMA production was
      correlated with the abundance of methanogens, whereas equol production correlated
      with sulfate-reducing bacteria, indicating that the metabolic fate of daidzein
      may be related to intestinal H(2) metabolism.

PMID- 17506825
TI  - The bacterivory of interstitial ciliates in association with bacterial biomass
      and production in the hyporheic zone of a lowland stream.
AB  - Rates of bacteria ingestion by interstitial ciliates were estimated and compared
      to bacterial biomass and production. Investigation was carried out in the
      hyporheic zone of a lowland stream. FISH was applied to quantitatively determine
      bacteria within the ciliate's food vacuoles. To estimate bacteria ingestion rates
      using FISH, we had to strike a new path. When numbers of bacteria in the food
      vacuoles remains constant with time (bacterial digestion and ingestion are at
      equilibrium), ingestion rate can be estimated based on the digestion time and the
      average number of bacteria per cell. Ciliate community was predominantly composed
      of bacterivorous ciliates. FISH-signals deriving from ingested bacteria were
      detected in Cinetochilum margaritaceum, 'other small scuticociliates', Pleuronema
      spp., and Vorticella spp. Ingestion rates for these taxa were 78, 150, 86, and 38
      bacteria ind(-1) h(-1), respectively. The grazing impacts on bacterial biomass
      and carbon production were calculated based on these ingestion rates. Ciliate
      grazing caused a decrease in bacterial biomass of 0.024% day(-1) and in bacterial
      carbon production of 1.60%. These findings suggest that interstitial ciliate
      grazing impact on bacteria biomass and production was too low to represent an
      important link in the carbon flow of the hyporheic zone under study.

PMID- 17506826
TI  - Lactobacillus gasseri Gasser AM63(T) degrades oxalate in a multistage continuous
      culture simulator of the human colonic microbiota.
AB  - Colonic oxalate-degrading bacteria have been shown to play an important role in
      human kidney stone formation. In this study, molecular analysis of the
      Lactobacillus gasseri genome revealed a cluster of genes encoding putative formyl
      coenzyme A transferase (frc) and oxalyl coenzyme A decarboxylase (oxc)
      homologues, possibly involved in oxalate degradation. The ability of
      Lactobacillus gasseri Gasser AM63(T) to degrade oxalate was confirmed in vitro.
      Transcription of both genes was induced by oxalate, and reverse transcription-PCR
      confirmed that they were co-transcribed as an operon. A three-stage continuous
      culture system (CCS) inoculated with human fecal bacteria was used to model
      environmental conditions in the proximal and distal colons, at system retention
      times within the range of normal colonic transit rates (30 and 60 hours). A
      freeze-dried preparation of L. gasseri was introduced into the CCS under steady
      state growth conditions. Short chain fatty acid analysis indicated that addition
      of L. gasseri to the CCS did not affect the equilibrium of the microbial
      ecosystem. Oxalate degradation was initiated in the first stage of the CCS,
      corresponding to the proximal colon, suggesting that this organism may have
      potential therapeutic use in managing oxalate kidney stone disease in humans.

PMID- 17506827
TI  - Bacterial community composition of a shallow hypertrophic freshwater lake in
      China, revealed by 16S rRNA gene sequences.
AB  - The phylogenetic composition of a bacterial community from a hypertrophic
      freshwater lake in China was investigated by sequencing cloned 16S rRNA genes.
      Three hundred and thirty-six bacterial clones from four clone libraries in
      different months (March, May, July and September in 2004) were classified into
      142 operational taxonomic units, most of which were affiliated with bacterial
      divisions commonly found in freshwater ecosystem, e.g. Alpha-, Beta-, Gamma- and
      Deltaproteobacteria, Bacteriodetes and Actinobacteria. The results showed that
      the composition of bacterial community in the July library was the most diverse
      one. Actinobacteria was the most significant lineage in Lake Taihu, with dominant
      numbers of operational taxonomic units in the May, July and September libraries.
      Phylogenetic analysis suggested that 53 sequences were grouped into six novel
      clusters which may represent specific populations indigenous to the environment.
      Coverage analyses indicated that the clone libraries could provide a fine
      inventory of bacterial diversity in the lake.

PMID- 17506829
TI  - The presence of the cyanobacterial toxin microcystin in black band disease of
      corals.
AB  - Black band disease (BBD) is a migrating, cyanobacterial dominated, sulfide-rich
      microbial mat that moves across coral colonies lysing coral tissue. While it is
      known that BBD sulfate-reducing bacteria contribute to BBD pathogenicity by
      production of sulfide, additional mechanisms of toxicity may be involved. Using
      HPLC/MS, the cyanotoxin microcystin was detected in 22 field samples of BBD
      collected from five coral species on nine reefs of the wider Caribbean (Florida
      Keys and Bahamas). Two cyanobacterial cultures isolated from BBD, Geitlerinema
      and Leptolyngbya sp. contained microcystin based on HPLC/MS, with toxic activity
      confirmed using the protein phosphatase inhibition assay. The gene mcyA from the
      microcystin synthesis complex was detected in two field samples and from both BBD
      cyanobacterial cultures. Microcystin was not detected in six BBD samples from a
      different area of the Caribbean (St Croix, USVI) and the Philippines, suggesting
      regional specificity for BBD microcystin. This is the first report of the
      presence of microcystin in a coral disease.

PMID- 17506828
TI  - The influence of ultramafic rocks on microbial communities at the Logatchev
      hydrothermal field, located 15 degrees N on the Mid-Atlantic Ridge.
AB  - The ultramafic-hosted Logatchev hydrothermal field (LHF) on the Mid-Atlantic
      Ridge is characterized by high hydrogen and methane contents in the subseafloor,
      which support a specialized microbial community of phylogenetically diverse,
      hydrogen-oxidizing chemolithoautotrophs. We compared the prokaryotic communities
      of three sites located in the LHF and encountered a predominance of archaeal
      sequences affiliated with methanogenic Methanococcales at all three. However, the
      bacterial composition varied in accordance with differences in fluid chemistry
      between the three sites investigated. An increase in hydrogen seemed to coincide
      with the diversification of hydrogen-oxidizing bacteria. This might indicate that
      the host rock indirectly selects this specific group of bacteria. However, next
      to hydrogen availability further factors are evident (e.g. mixing of hot reduced
      hydrothermal fluids with cold oxygenated seawater), which have a significant
      impact on the distribution of microorganisms.

PMID- 17506830
TI  - A functional analysis of the Candida albicans homolog of Saccharomyces cerevisiae
      VPS4.
AB  - To investigate the role of the prevacuolar secretion pathway in the trafficking
      of vacuolar proteins in Candida albicans, the C. albicans homolog of the
      Saccharomyces cerevisiae vacuolar protein sorting gene VPS4 was cloned and
      analyzed. Candida albicans VPS4 encodes a deduced AAA-type ATPase that is 75.6%
      similar to S. cerevisiae Vps4p, and plasmids bearing C. albicans VPS4
      complemented the abnormal vacuolar morphology and carboxypeptidase missorting in
      S. cerevisiae vps4 null mutants. Candida albicans vps4Delta null mutants
      displayed a characteristic class E vacuolar morphology and multilamellar
      structures consistent with an aberrant prevacuolar compartment. The C. albicans
      vps4Delta mutant degraded more extracellular bovine serum albumin than did wild
      type strains, which implied that this mutant secreted more extracellular protease
      activity. These phenotypes were complemented when a wild-type copy of VPS4 was
      reintroduced into its proper locus. Using a series of protease inhibitors, the
      origin of this extracellular protease activity was identified as a serine
      protease, and genetic analyses using a C. albicans vps4Deltaprc1Delta mutant
      identified this missorted vacuolar protease as carboxypeptidase Y. Unexpectedly,
      C. albicans Sap2p was not detected in culture supernatants of the vps4Delta
      mutants. These results indicate that C. albicans VPS4 is required for vacuolar
      biogenesis and proper sorting of vacuolar proteins.

PMID- 17506831
TI  - Pseudozyma jejuensis sp. nov., a novel cutinolytic ustilaginomycetous yeast
      species that is able to degrade plastic waste.
AB  - An ustilaginomycetous anamorphic yeast, isolated from orange leaves on Jeju
      island in South Korea, represents a novel Pseudozyma species according to
      morphologic and physiologic findings and molecular taxonomic analysis using the
      D1/D2 domains of the large subunit (26S) rRNA gene and the internally transcribed
      spacer (ITS) 1+2 regions. The name Pseudozyma jejuensis sp. nov. is proposed for
      this novel species, with OL71(T) (=KCTC 17482(T)=CBS 10454(T)) as type strain. In
      the present study, we have also demonstrated that Pseudozyma jejuensis OL71 is
      capable of producing cutinase and degrading polycaprolactone. These results
      suggest that Pseudozyma jejuensis or its cutinase may be useful for the
      biological degradation of plastic waste.

PMID- 17506832
TI  - A new regulatory element mediates ethanol repression of KlADH3, a Kluyveromyces
      lactis gene coding for a mitochondrial alcohol dehydrogenase.
AB  - KlADH3 is a Kluyveromyces lactis alcohol dehydrogenase gene induced in the
      presence of all respiratory carbon sources except ethanol, which specifically
      represses this gene. Deletion analysis of the KlADH3 promoter revealed the
      presence of both positive and negative elements. However, by site-directed
      mutagenesis and gel retardation experiments, we identified a 15-bp element
      responsible for the transcriptional repression of this gene by ethanol. In
      particular, this element showed putative sites required for the sequential
      binding of ethanol-induced factors responsible for the repressed conditions, and
      the binding of additional factors relieved repression. In addition, we showed
      that the ethanol element was required for in vivo repression of KlAdh3 activity.

PMID- 17506833
TI  - Kluyveromyces lactis sexual pheromones. Gene structures and cellular responses to
      alpha-factor.
AB  - The Kluyveromyces lactis genes for sexual pheromones have been analyzed. The
      alpha-factor gene encodes a predicted polypeptide of 187 amino acid residues
      containing four tridecapeptide repeats (WSWITLRPGQPIF). A nucleotide blast search
      of the entire K. lactis genome sequence allowed the identification of the
      nonannotated putative a-pheromone gene that encodes a predicted protein of 33
      residues containing one copy of the dodecapeptide a-factor (WIIPGFVWVPQC). The
      role of the K. lactis structural genes KlMFalpha1 and KlMFA1 in mating has been
      investigated by the construction of disruption mutations that totally eliminate
      gene functions. Mutants of both alleles showed sex-dependent sterility,
      indicating that these are single-copy genes and essential for mating. MATalpha,
      Klsst2 mutants, which, by analogy to Saccharomyces cerevisiae, are defective in
      Galpha-GTPase activity, showed increased sensitivity to synthetic alpha-factor
      and increased capacity to mate. Additionally, Klbar1 mutants (putatively
      defective in alpha-pheromone proteolysis) showed delay in mating but sensitivity
      to alpha-pheromone. From these results, it can be deduced that the K. lactis MATa
      cell produces the homolog of the S. cerevisiaealpha-pheromone, whereas the
      MATalpha cell produces the a-pheromone.

PMID- 17506834
TI  - Mutations in the RAD27 and SGS1 genes differentially affect the chronological and
      replicative lifespan of yeast cells growing on glucose and glycerol.
AB  - The Sgs1 protein from Saccharomyces cerevisiae is a member of the RecQ helicases.
      Defects in RecQ helicases result in premature aging phenotypes in both yeasts and
      humans, which appear to be promoted by replicative stress. Yeast rad27 mutants
      also suffer from premature aging. As the human Rad27p and Sgs1p homologs
      interact, a similar interaction between the yeast proteins could be important for
      promoting longevity in S. cerevisiae. We tested the contribution of a potential
      interaction between Rad27p and Sgs1p to longevity by analyzing lifespan and
      parameters associated with longevity in rad27 and sgs1 mutants. The carbon source
      supporting growth also modulated longevity as evaluated by replicative and
      chronological lifespan measurements. Growth on glycerol promoted chronological
      lifespan, while maximum replicative lifespan was obtained with glucose-supported
      growth. In comparison to the individual mutants, the sgs1 rad27 double mutant
      displayed a shortened replicative lifespan and was also more sensitive to DNA
      damaging agents. In addition to promoting replicative lifespan, the activity of
      Rad27p was critical for achieving full chronological lifespan. The rad27 mutants
      exhibited increased oxidative stress levels along with an elevated spontaneous
      mutation rate. Removal of Sgs1p activity additionally increased the oxidative
      stress and spontaneous mutation rate in rad27 mutants without affecting the
      chronological lifespan.

PMID- 17506835
TI  - Autoimmune hepatitis complicated by late-onset systemic lupus erythematosus.
AB  - A 69-year-old man with autoimmune hepatitis (AIH) was admitted to hospital with
      high fever and cough. Chest roentgenogram and computed tomography showed pleural
      and pericardial effusion. Serological tests showed a high titer of antinuclear
      antibodies and positive anti-DNA antibody and lymphocytopenia. He fulfilled the
      American College of Rheumatology criteria for systemic lupus erythematosus (SLE).
      After administration of corticosteroids, his symptoms and liver dysfunction
      improved. To the authors' knowledge, this is the first male case of overlap
      between AIH and late-onset SLE.

PMID- 17506836
TI  - Novel approaches to assessing renal function in cirrhotic liver disease.
AB  - Renal dysfunction is common in patients with end-stage liver disease. Etiological
      factors include conditions as diverse as acute tubular necrosis, immunoglobulin A
      nephropathy and hepatorenal syndrome. Current standard tests of renal function,
      such as measurement of serum urea and creatinine levels, are inaccurate as the
      synthesis of these markers is affected by the native liver pathology. This
      article reviews novel markers of renal function and their potential use in
      patients with liver disease.

PMID- 17506837
TI  - Hypofractionated stereotactic radiotherapy with and without transarterial
      chemoembolization for small hepatocellular carcinoma not eligible for other
      ablation therapies: Preliminary results for efficacy and toxicity.
AB  - AIM: To investigate the efficacy and toxicity of hypofractionated stereotactic
      radiotherapy for the treatment of patients presenting with hepatocellular
      carcinoma (HCC) in a single institutional setting. METHODS: Sixteen patients who
      presented with solitary HCC, including two patients with a tumor thrombus of the
      portal veins, were treated with stereotactic radiotherapy with or without
      transarterial chemoembolization. The criteria for stereotactic radiotherapy were
      existence of technical difficulties for other ablation therapies, inoperable
      disease or refusal to undergo surgery, tumor staged as Grade A or B according to
      the Child-Pugh classification, and solitary tumor distant from the
      gastrointestinal tract and kidney with a tumor volume <100 cm(3). In 14 of 16
      patients, a total dose of 35- 50 Gy was delivered in 5-7 fractions over 5-9 days.
      RESULTS: At the end of a mean follow-up of 612 days (median 611 days; range 244
      994 days), all patients were alive. Eight of 16 patients had complete responses
      and seven others were judged as stable with lipiodol accumulation. In one
      patient, local recurrence developed after 489 days. Intrahepatic recurrences
      developed outside the treated volume in six patients and no extrahepatic
      metastases developed during follow-up. No serious treatment-related toxic
      manifestations developed. CONCLUSIONS: Stereotactic radiotherapy for HCC with or
      without transarterial chemoembolization is feasible therapy and provides good
      local control with a short treatment period. Stereotactic radiotherapy may be of
      clinical benefit in patients who are inoperable or for whom there are
      difficulties in other ablation therapies.

PMID- 17506838
TI  - Comment on treatment of incidental adnexal masses at cesarean section: a
      retrospective study.

PMID- 17506839
TI  - Thoracotomy for the management of recurrent vaginal leiomyosarcoma.
AB  - Vaginal leiomyosarcoma is a rare malignancy for which little data exists to guide
      treatment decisions. We describe a patient diagnosed with primary vaginal
      leiomyosarcoma who underwent hysterectomy and upper vaginectomy followed by whole
      pelvic radiation. Approximately 3 months after her initial treatment, she
      presented with an isolated pulmonary recurrence, which resolved after 12 cycles
      of chemotherapy. Nineteen months later, a second recurrence was found at the same
      site. This metastasis was resected and she has remained without evidence of
      further disease for more than 24 months. Similar to patients diagnosed with
      uterine sarcomas, resection of pulmonary metastases may offer women with
      recurrent vaginal leiomyosarcoma improved survival with good quality of life.
      Thoracotomy should be considered for women diagnosed with pulmonary recurrences
      of this disease.

PMID- 17506841
TI  - Primary retroperitoneal mucinous cystadenocarcinomas are a distinct entity.
AB  - Primary retroperitoneal mucinous cystadenocarcinomas are rare tumors with a
      controversial pathogenesis. Present report describes a 74-year-old woman with a
      retroperitoneal cystic pelvic mass. Her past medical history included
      appendectomy, bilateral salpingo-oophorectomy, and a hysterectomy. An explorative
      laparotomy was performed and the mass was completely excised. Definitive
      pathology revealed a primary retroperitoneal mucinous cystadenocarcinoma of the
      ovarian type. Further management consisted of four cycles carboplatin. She had a
      recurrence after 8 months and died 31 months after the initial diagnosis. Primary
      retroperitoneal mucinous cystadenocarcinomas are distinct entity, with the same
      poor prognosis as their ovarian counterpart.

PMID- 17506842
TI  - Accuracy of telomerase in cervical lesions: a systematic review.
AB  - The detection of telomerase activity in cervix may provide information on
      cervical carcinogenesis and may be a marker to monitor cervical intraepithelial
      neoplasia transition. A quantitative systematic review was performed to estimate
      the accuracy of telomerase assay in cervical lesions. Studies that evaluated the
      telomerase test (telomerase repeated amplification protocol) for the diagnosis of
      cervix lesions and compared it to paraffin-embedded sections as the diagnostic
      standard were included. Ten studies were analyzed, which included 1069 women. The
      diagnostic odds ratio (DOR) for a positive telomerase test for low-grade squamous
      intraepithelial lesions (Lo-SIL) vs normal or benign lesions was 3.2 (95% CI, 1.9
      5.6). The DOR for a positive telomerase test for high-grade squamous
      intraepithelial lesions (Hi-SIL) vs Lo-SIL, normal or benign lesions was 5.8 (95%
      CI, 3.1-10). For cervix cancer vs Hi-SIL, the DOR for a positive telomerase test
      was 8.1 (95% CI, 3.2-20.3) and for cervix cancer vs Lo-SIL, normal or benign
      lesions, it was 40.9 (95% CI, 18.2-91). Our data support the current hypothesis
      that telomerase may activate an early event in cervical carcinogenesis that could
      be associated with the initiation and progression of cervical lesions.

PMID- 17506843
TI  - Quantitative real-time polymerase chain reaction analysis of the type
      distribution, viral load, and physical status of human papillomavirus in liquid
      based cytology samples from cervical lesions.
AB  - Human papillomavirus (HPV) 16 DNA can be integrated into the DNA of cells,
      thereby disrupting E2 gene expression, which leads to increased expression of the
      E6 and E7 viral oncogenes and progression to cancer. However, the relationships
      among HPV viral load, cytologic diagnosis, and HPV integration status remain
      unclear. The aim of this study was to evaluate the HPV type distribution, viral
      load, and HPV 16 integration status, and then investigate their relationships
      with precancerous and cancerous lesions among Japanese women of different age
      groups. Liquid-based cytology (LBC) samples were examined by quantitative real
      time polymerase chain reaction (PCR). The overall mean prevalences of HPV were
      higher in younger women and lower in middle-aged women among the age groups. The
      positivity rate of HPV 16 peaked at a younger age than that of all HPV subtypes.
      The HPV 16 viral load per cell decreased from a low-grade squamous
      intraepithelial lesion (LSIL) to a cancerous lesion (257.4 for LSIL, 76.9 for
      high-grade squamous intraepithelial lesions, and 35.7 for cancerous lesions). The
      average HPV 16 DNA copy numbers for three different HPV 16 integration statuses
      were 64.1 for the episomal form, 465.5 for the mixed form, and 0.4 for the
      integrated form. Furthermore, the mean age of patients with the pure integrated
      form of HPV 16 was more than 10 years older than those of patients with the
      episomal and mixed forms. Quantitative real-time PCR appears to be a useful
      method for quantitative and physical status analyses of HPV in cervical cancer
      screening with LBC samples.

PMID- 17506844
TI  - A feasibility study of low-dose, prolonged oral topotecan in patients with
      advanced ovarian, fallopian tube, or primary peritoneal serous cancer who have
      attained a complete clinical response following platinum-based chemotherapy.
AB  - To determine the tolerability of oral maintenance topotecan when administered to
      patients with advanced ovarian, fallopian tube, and primary peritoneal serous
      cancers who have achieved a complete clinical response after first-line platinum
      based therapy. Oral topotecan was given at a starting dose of 0.4 mg/m(2)/dose,
      twice a day (BID) for 21 consecutive days out of 28 days. The dose was
      subsequently increased to 0.5 mg/m(2)/dose, twice a day as tolerated. If the
      patient experienced toxicities during cycle 1 or subsequent cycles, doses were
      delayed and/or reduced. The lowest dose allowed on protocol was 0.3 mg/m(2)/dose
      twice daily. Thirteen patients were enrolled in the study, representing a total
      of fifty-nine cycles of oral topotecan. The starting dose of 0.4 mg/m(2) by mouth
      (PO) BID for 21 days was generally difficult for patients to tolerate, usually
      due to progressive anemia and fatigue, and a dose reduction to 0.3 mg/m(2) was
      necessary in 10/13 patients. A median of six cycles was administered, although 6
      of 13 patients could not tolerate the planned 6 cycles due to toxicity.
      Hematologic toxicity was the most common side effect, although there were no
      episodes of febrile neutropenia. Diarrhea was the most common nonhematologic side
      effect, occurring in 8 of 13 patients. Six patients were removed from the study
      prior to completing the planned six cycles of therapy, after receiving a median
      number of 2.5 cycles of treatment. This dose and schedule of oral topotecan does
      not appear to be feasible in this patient population.

PMID- 17506845
TI  - Giant ovarian cysts: is a pre- and intraoperative drainage an advisable
      procedure?

PMID- 17506846
TI  - Cold knife versus laser cone biopsy for adenocarcinoma in situ of the cervix--a
      comparison of management and outcome.
AB  - Eighty-two patients with adenocarcinoma in situ of the cervix managed at Royal
      Prince Alfred Hospital were reviewed and data were collected on those treated by
      cold knife cone biopsy (n= 38) and laser cone biopsy (n= 44). No differences were
      found in patient age, cytologic or referral history, or outcomes. Having laser
      excision did not compromise margin status or subsequent management. Invasive
      disease was found in 24 patients, 16 of whom were managed conservatively with
      good outcome. Twelve of these were in the laser cone group. In those patients
      from both groups managed conservatively, there was only one recurrence, squamous
      preinvasive disease after 8 years. Laser cone biopsy is as effective as cold
      knife cone biopsy with no compromise of outcome for these patients.

PMID- 17506847
TI  - Synchronous primary cancers of the endometrium and ovary.
AB  - Simultaneous detection of malignancy in the endometrium and ovary represents an
      uncommon event. The objective of the study was to clarify the possible factors
      that influenced on the survival. From 1977 to 2005, totally 27 patients fulfilled
      the criteria and were included in the study. The medical records and the
      pathologic reports were reviewed. The histologic determination was followed by
      the World Health Organization Committee classification, and cancer stage was
      based on the staging system of the FIGO. The Kaplan-Meier survival analyses were
      generated and compared by the log-rank test. The incidence of synchronous primary
      endometrial and ovarian cancers was 3.3% in patients with endometrial cancer and
      2.7% in patients with ovarian cancer. The mean survival in the group of similar
      histology (n= 15) was 63 months, and 48 months in the group of dissimilar
      histology (n= 12) (P= 0.63). The mean survival in the group of early stage (n=
      21) was 68 months and 15 months in the group of advanced stage (n= 6) with
      statistic significance (P= 0.0003). However, the impact of adjuvant therapy on
      survival did not reach statistic significance (P= 0.15 for chemotherapy; P= 0.69
      for radiotherapy). We conclude that the majority of the patients belonged to
      concordant endometrioid histology in endometrium and ovary, and it tends to be
      early stage and low grade with favorable prognosis. The stage had more
      significant influence on the survival than the histology. Adjuvant therapy should
      be given especially in patients with advanced stage although the optimal
      management remained to be determined.

PMID- 17506848
TI  - Port-site and liver metastases after laparoscopic pelvic and para-aortic lymph
      node dissection for surgical staging of locally advanced cervical cancer.
AB  - Recently, we experienced a case of port-site and liver metastases after 75 cases
      of laparoscopic transperitoneal pelvic lymph node dissection (PLND) and para
      aortic lymph node dissection (PALND) for surgical staging of locally advanced
      cervical cancer. A 45-year-old-woman with stage IIB cervical adenocarcinoma
      underwent laparoscopic PLND and PALND for surgical staging. There was no
      intraperitoneal disease and cervical tumor was not manipulated at the time of
      laparoscopic surgery. Pathologic examination revealed only one micrometastasis in
      left internal iliac lymph node (LN), measuring 1 mm, of the 60 pelvic and para
      aortic LNs removed. She received concurrent chemoradiation therapy and pelvic
      mass disappeared completely. One month after the completion of therapy, both
      lateral and umbilical port-site and liver metastases were detected. We conclude
      that although cases of port-site metastasis have mostly occurred after extensive
      disease, the possibility of such complication should be kept in mind at
      laparoscopy of early cancer and laparoscopy which does not manipulate primary
      tumor.

PMID- 17506849
TI  - Correlation of recurrence rates and times with posttreatment human papillomavirus
      status in patients treated with loop electrosurgical excision procedure
      conization for cervical squamous intraepithelial lesions.
AB  - The aim of the present study was to assess recurrence rates and times in patients
      with squamous intraepithelial lesion (SIL) of the uterine cervix treated with
      loop electrosurgical excision procedure (LEEP) conization, in order to define
      categories of patients who have a different risk of recurrence and who need a
      different surveillance protocol. This study was carried out on 119 consecutive
      patients who underwent LEEP. All patients were followed up with cervical smear
      and colposcopy after 3, 6, and 12 months in the first-year posttreatment, and
      every 6-12 months afterwards. Human papillomavirus (HPV) testing was performed at
      the time of LEEP and repeated 3-6 months later. The histologic examination of
      LEEP specimens revealed stage IA1 squamous cell cervical cancer in 4 (3.4%)
      cases, high-grade SIL in 75 (63%) cases, and low-grade SIL in 40 (33.6%) cases.
      The four patients with stage IA1 cervical cancer were not included in the further
      analyses. Disease recurred in none of the 50 patients with negative posttreatment
      HPV testing, in 4 (9.3%) of the 43 patients with positive posttreatment HPV
      testing and negative surgical margins, and in 8 (36.4%) of 22 patients with
      positive posttreatment HPV testing and positive margins. The combined evaluation
      of surgical margin status and posttreatment HPV testing could allow to subdivide
      patients treated with LEEP into categories at different risk of recurrence,
      requiring new tailored surveillance procedures.

PMID- 17506850
TI  - Gene transcription during exposure to, and recovery from, cold and desiccation
      stress in Drosophila melanogaster.
AB  - We exposed adult male Drosophila melanogaster to cold, desiccation or starvation,
      and examined expression of several genes during exposure and recovery. Frost was
      expressed during recovery from cold, and was up-regulated during desiccation.
      Desiccation and starvation (but not cold) elicited increased expression of the
      senescence-related gene smp-30. Desat2 decreased during recovery from
      desiccation, but not in response to starvation or cold. Hsp70 expression
      increased after 1 h of recovery from cold exposure, but was unchanged in response
      to desiccation or starvation stress, and Hsp23 levels did not respond to any of
      the stressors. We conclude that D. melanogaster's responses to cold and
      desiccation are quite different and that care must be taken to separate exposure
      and recovery when studying responses to environmental stress.

PMID- 17506851
TI  - Manual superscaffolding of honey bee (Apis mellifera) chromosomes 12-16:
      implications for the draft genome assembly version 4, gene annotation, and
      chromosome structure.
AB  - The euchromatic arms of the five smallest telocentric chromosomes in the honey
      bee genome draft Assembly v4 were manually connected into superscaffolds. This
      effort reduced chromosomes 12-16 from 30, 21, 25, 42, and 21 mapped scaffolds to
      five, four, five, six, and five superscaffolds, respectively, and incorporated
      178 unmapped contigs and scaffolds totalling 2.6 Mb, a 6.4% increase in length.
      The superscaffolds extend from the genetically mapped location of the centromere
      to their identified distal telomeres on the long arms. Only two major
      misassemblies of 146 kb and 65 kb sections were identified in this 23% of the
      mapped assembly. Nine duplicate gene models on chromosomes 15 and 16 were made
      redundant, while another 15 gene models were improved, most spectacularly the MAD
      (MAX dimerization protein) gene which extends across 11 scaffolds for at least
      400 kb.

PMID- 17506852
TI  - Genomic and evolutionary analyses of Tango transposons in Aedes aegypti,
      Anopheles gambiae and other mosquito species.
AB  - Tango is a transposon of the Tc1 family and was originally discovered in the
      African malaria mosquito, Anopheles gambiae. Here we report a systematic analysis
      of the genome sequence of the yellow fever mosquito, Aedes aegypti, which
      uncovered three distinct Tango transposons. We name the only An. gambiae Tango
      transposon AgTango1 and the three Ae. aegypti Tango elements AeTango1-3. Like
      AgTango1, AeTango1 and AeTango2 elements both have members that retain
      characteristics of autonomous elements such as intact open reading frames and
      terminal inverted repeats (TIRs). AeTango3 is a degenerate transposon with no
      full-length members. All full-length Tango transposons contain subterminal direct
      repeats within their TIRs. AgTango1 and AeTango1-3 form a single clade among
      other Tc1 transposons. Within this clade, AgTango1 and AeTango1 are closely
      related and share approximately 80% identity at the amino acid level, which
      exceeds the level of similarity of the majority of host genes in the two species.
      A survey of Tango in other mosquito species was carried out using degenerate PCR.
      Tango was isolated and sequenced in all members of the An. gambiae species
      complex, Aedes albopictus and Ochlerotatus atropalpus. Oc. atropalpus contains a
      rich diversity of Tango elements, while Tango elements in Ae. albopictus and the
      An. gambiae species complex all belong to Tango1. No Tango was detected in Culex
      pipiens quinquefasciatus, Anopheles stephensi, Anopheles dirus, Anopheles farauti
      or Anopheles albimanus using degenerate PCR. Bioinformatic searches of the Cx. p.
      quinquefasciatus (~10 x coverage) and An. stephensi (0.33 x coverage) databases
      also failed to uncover any Tango elements. Although other evolutionary scenarios
      cannot be ruled out, there are indications that Tango1 underwent horizontal
      transfer among divergent mosquito species.

PMID- 17506854
TI  - Dilated cardiomyopathy following right ventricular pacing for AV block in young
      patients: resolution after upgrading to biventricular pacing systems.

PMID- 17506853
TI  - Chronic intranasal administration of mould spores or extracts to unsensitized
      mice leads to lung allergic inflammation, hyper-reactivity and remodelling.
AB  - Allergic asthma is a serious multifaceted disease characterized by eosinophil
      rich airway inflammation, airway hyperreactivity and airway wall modifications
      known as remodelling. We previously demonstrated that the spores of two
      allergenic moulds, Alternaria alternata and Cladosporium herbarum, were potent
      inducers of immunoglobulin E (IgE) production. Moreover, mice sensitized by two
      intraperitoneal injections before intranasal challenge with A. alternata or C.
      herbarum spores developed an allergic lung inflammation and hyperreactivity. Here
      we report on the effect of chronic intranasal administration of C. herbarum
      spores or A. alternata extracts to unsensitized BALB/c mice. Our results
      demonstrate that this chronic treatment led to an increase of total serum IgE and
      the appearance of specific IgE and IgG1. Total cell number in bronchoalveolar
      lavage fluid from treated mice was highly increased compared to phosphate
      buffered-saline-treated mice because of the accumulation of macrophages,
      neutrophils, lymphocytes and eosinophils. Airway hyperreactivity appeared after 3
      weeks (extract) and 7 weeks (spores) and was maintained during the whole
      treatment. Increased interleukin-13 mRNA expression in the lungs and T helper
      type 2 cytokines (interleukin-4, -5, -6 and -13) and transforming growth factor
      beta secretion in bronchoalveolar lavage fluid were also observed. Lung
      hydroxyproline and fibronectin contents indicated increased fibrosis in mice
      treated with mould allergen. These observations were confirmed by histological
      analysis demonstrating airway wall remodelling and strong mucus production. These
      observations show that this model, using chronic intranasal administration of
      relevant particulate allergens, is an interesting tool for the study of
      mechanisms leading to allergic pulmonary diseases and lung remodelling.

PMID- 17506855
TI  - The effect of antihistamine cetirizine on ventricular repolarization in
      congenital long QT syndrome.
AB  - INTRODUCTION: Many drugs are known to block cardiac potassium channels, thus
      prolonging QT interval and predisposing to malignant arrhythmias. Patients with
      congenital long QT syndrome are particularly vulnerable, but usually
      electrophysiological effects of drugs have not been assessed in these patients at
      risk. METHODS: Fifteen asymptomatic patients with type 1 (LQT1), 15 patients with
      type 2 (LQT2) long QT syndrome, and 15 healthy volunteers took a placebo and
      cetirizine 10 mg. In addition, healthy volunteers took cetirizine 50 mg. The
      study was single-blinded and randomized. Exercise tests were performed during
      stable plasma concentrations. The electrocardiogram was recorded with a body
      surface potential mapping system (BSPM). Data were analyzed with an automated
      analyze program. QT intervals to the T wave apex and T wave end and their
      difference (Tp-e) were determined at rest and at specified heart rates during and
      after exercise. RESULTS: Cetirizine did not lengthen the QT intervals at rest or
      during exercise and recovery in any group. It shortened Tp-e at rest in LQT1 and
      LQT2 patients and during exercise test in LQT1 patients, thus slightly decreasing
      electrocardiographic transmural dispersion of repolarization. CONCLUSIONS:
      Cetirizine does not adversely modify ventricular repolarization in types 1 and 2
      long QT syndrome, suggesting that it might be used safely in these long QT
      syndrome patients.

PMID- 17506856
TI  - ICD shocks in a Brugada syndrome patient: what is the mechanism?

PMID- 17506857
TI  - Reduction of AF recurrence after pulmonary vein isolation by eliminating ATP
      induced transient venous re-conduction.
AB  - BACKGROUND: Recent evidence has suggested that the transient re-conduction of the
      isolated pulmonary vein (PV) induced by the intravenous injection of adenosine
      (dormant PV conduction) might predict the incidence of subsequent venous
      reconnection after the procedure, which is the main cause of the atrial
      fibrillation (AF) recurrence after PV isolation (PVI). We tested the hypothesis
      that the elimination of these dormant PV conductions by additional radiofrequency
      (RF) applications can improve the efficacy of the PVI. METHODS AND RESULTS: One
      hundred forty-eight patients (124 males; mean age 53 +/- 9 years) with drug
      refractory AF underwent the PVI procedure. The standard PVI was performed in 94
      patients (Group A), whereas the elimination of adenosine triphosphate (ATP)
      induced dormant conduction using additional RF energy was performed in addition
      to the standard PVI in other 54 patients (Group B). Dormant conduction was
      observed in 56% of the patients (30/54) in Group B and 95% of these transient re
      conductions were successfully eliminated by additional RF applications (mean: 1.5
      +/- 1.0 times). During the mean follow-up period of 20 months, recurrences of AF
      after the procedures were observed significantly less frequently in Group B (20%)
      than in Group A (40%) (P < 0.05). CONCLUSION: The use of additional RF
      applications to eliminate transient PV reconnection induced by ATP injection led
      to a reduction of AF recurrence after PVI, most likely due to the minimization of
      the subsequent PV reconnection.

PMID- 17506859
TI  - p25/cyclin-dependent kinase 5 promotes the progression of cell death in nucleus
      of endoplasmic reticulum-stressed neurons.
AB  - Dysregulation of cyclin-dependent kinase 5 (Cdk5) by cleavage of its activator
      p35 to p25 by calpain is involved in the neuronal cell death observed in
      neurodegenerative disorders, including Alzheimer's disease. However, it is not
      yet clear how p25/Cdk5 induces cell death, although its cytosolic localization or
      extended half life are thought to be involved. We show here that endoplasmic
      reticulum (ER) stress causes the calpain-dependent cleavage of p35 to p25 in
      primary cultured cortical neurons. Generation of p25 occurred at a cell death
      execution step in ER-stressed neurons. p25 translocated to the nucleus in ER
      stressed neurons, whereas p35/Cdk5 was perinuclear in control neurons. Cdk5
      inhibitors or dominant-negative Cdk5 suppressed ER stress-induced neuronal cell
      death. These findings indicate that p25/Cdk5 is a proapoptotic factor that
      promotes ER stress-induced neuronal cell death in nuclei.

PMID- 17506858
TI  - Plasma serotonin levels and the platelet serotonin transporter.
AB  - Serotonin (5HT) is a platelet-stored vasoconstrictor. Altered concentrations of
      circulating 5HT are implicated in several pathologic conditions, including
      hypertension. The actions of 5HT are mediated by different types of receptors and
      terminated by a single 5HT transporter (SERT). Therefore, SERT is a major
      mechanism that regulates plasma 5HT levels to prevent vasoconstriction and
      thereby secure a stable blood flow. In this study, the response of platelet SERT
      to the plasma 5HT levels was examined within two models: (i) in subjects with
      chronic hypertension or normotension; (ii) on platelets isolated from
      normotensive subjects and pretreated with 5HT at various concentrations. The
      platelet 5HT uptake rates were lower during hypertension due to a decrease in
      Vmax with a similar Km; also, the decrease in Vmax was primarily due to a
      decrease in the density of SERT on the platelet membrane, with no change in whole
      cell expression. Additionally, while the platelet 5HT content decreased 33%, the
      plasma 5HT content increased 33%. Furthermore, exogenous 5HT altered the 5HT
      uptake rates by changing the density of SERT molecules on the plasma membrane in
      a biphasic manner. Therefore, we hypothesize that in a hypertensive state, the
      elevated plasma 5HT levels induces a loss in 5HT uptake function in platelets via
      a decrease in the density of SERT molecules on the plasma membrane. Through the
      feedback effect of this proposed mechanism, plasma 5HT controls its own
      concentration levels by modulating the uptake properties of platelet SERT.

PMID- 17506860
TI  - Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain
      neurons in vitro.
AB  - The transcription factor Nurr1 is essential for the generation of midbrain
      dopaminergic neurons (mDA). Only a few Nurr1-regulated genes have so far been
      identified and it remains unclear how Nurr1 influences the development and
      function of dopaminergic neurons. To identify novel Nurr1 target genes we have
      used genome-wide expression profiling in rat midbrain primary cultures, enriched
      in dopaminergic neurons, following up-regulation of Nurr1 expression by
      depolarization. In this study we demonstrate that following depolarization the
      hyperexpression of Nurr1 and the brain derived neurotrophic factor (BDNF) are
      phospholipase C- and protein kinase C-dependent. We show that Bdnf, which encodes
      a neurotrophin involved also in the phenotypic maturation of mDA neurons, is a
      novel Nurr1 target gene. By RNA interference experiments we show that a decreased
      Nurr1 expression is followed by tyrosine hydroxylase and BDNF mRNA and protein
      down-regulation. Reporter gene assay experiments performed on midbrain primary
      cultures using four Bdnf promoter constructs show that Bdnf is a direct target
      gene of Nurr1. Taken together, our findings suggest that Nurr1 might also
      influence the development and the function of midbrain dopaminergic neurons via
      direct regulation of Bdnf expression.

PMID- 17506862
TI  - "I have never taken performance enhancing drugs and I never will": drug discourse
      in the Shane Warne case.
AB  - This study investigates the discursive management of taking prohibited substances
      in sport. In particular, it explores how one high-profile athlete, Australian
      cricketer Shane Warne, accounted for his drug-taking behavior when talking to the
      media. Discursive psychology (DP) is used as the theoretical and methodological
      framework to study drug discourses in sport. Emphasis in DP is on making explicit
      how psychological concepts (e.g., drug explanations) are used in everyday talk to
      perform certain actions. The research data is Warne's first public press
      statement concerning his 2003 positive test for hydrochlorothiazide and
      amiloride. Analysis reveals that Warne constructed his drug taking as not being
      related to performance enhancement and substantiated this with a history of
      negative test results. Warne worked up his taking as the result of ignorance
      rather than deliberate deception. Further, he presented this as a one-off event
      and not reflective of systematic drug usage. It is argued in this study that to
      better understand drug taking in sport, sport researchers need to understand how
      athletes talk about drugs. For it is through talk that most sporting activities
      are conducted and maintained, and it is this talk that needs to be understood and
      analyzed.

PMID- 17506861
TI  - Yeast apurinic/apyrimidinic endonuclease Apn1 protects mammalian neuronal cell
      line from oxidative stress.
AB  - Reactive oxygen species (ROS) have been implicated as one of the agents
      responsible for many neurodegenerative diseases. A critical target for ROS is
      DNA. Most oxidative stress-induced DNA damage in the nucleus and mitochondria is
      removed by the base excision repair pathway. Apn1 is a yeast enzyme in this
      pathway which possesses a wider substrate specificity and greater enzyme activity
      than its mammalian counterpart for removing DNA damage, making it a good
      therapeutic candidate. For this study we targeted Apn1 to mitochondria in a
      neuronal cell line derived from the substantia nigra by using a mitochondrial
      targeting signal (MTS) in an effort to hasten the removal of DNA damage and
      thereby protect these cells. We found that following oxidative stress,
      mitochondrial DNA (mtDNA) was repaired more efficiently in cells containing Apn1
      with the MTS than controls. There was no difference in nuclear repair. However,
      cells that expressed Apn1 without the MTS showed enhanced repair of both nuclear
      and mtDNA. Both Apn1-expressing cells were more resistant to cell death following
      oxidative stress compared with controls. Therefore, these results reveal that the
      expression of Apn1 in neurons may be of potential therapeutic benefit for
      treating patients with specific neurodegenerative diseases.

PMID- 17506863
TI  - Modulation of cargo release from dense core granules by size and actin network.
AB  - During regulated fusion of secretory granules with the plasma membrane, a fusion
      pore first opens and then dilates. The dilating pore allows cargo proteins from
      the dense core to be released into the extracellular space. Using real-time
      evanescent field fluorescence microscopy of live PC12 cells, it was determined
      how rapidly proteins of different sizes escape from single granules after fusion.
      Tissue plasminogen activator (tPA)-Venus is released 40-fold slower than the
      three times smaller neuropeptide Y [NPY-monomeric GFP (mGFP)]. An NPY bearing two
      mGFPs in tandem [NPY-(mGFP)(2)] as an intermediate-sized fusion probe is released
      most slowly. Although, the time-course of release varies substantially for a
      given probe. Coexpression of beta-actin, actin-related protein 3 or mAbp1 slowed
      the release of the two larger cargo molecules but did not affect release of NPY
      mGFP or of the granule-membrane-bound probe Vamp-pHluorin. Additionally, high
      concentrations of cytochalasin D slowed release of the tPA-Venus. Together these
      results suggest that fusion pore dilation is not the only determinate of release
      time-course and that actin rearrangements similar to those mediating actin
      mediated motility influences the time-course of release without directly
      interfering with the granule membrane to cell membrane connection.

PMID- 17506864
TI  - Molecular basis for autoregulatory interaction between GAE domain and hinge
      region of GGA1.
AB  - Golgi-localizing, gamma-adaptin ear domain homology, ADP ribosylation factor
      binding (GGA) proteins and the adaptor protein (AP) complex, AP-1, are involved
      in membrane traffic between the trans Golgi network and the endosomes. The gamma
      adaptin ear (GAE) domain of GGAs and the gamma1 ear domain of AP-1 interact with
      an acidic phenylalanine motif found in accessory proteins. The GAE domain of GGA1
      (GGA1-GAE) interacts with a WNSF-containing peptide derived from its own hinge
      region, although the peptide sequence deviates from the standard acidic
      phenylalanine motif. We report here the structure of GGA1-GAE in complex with the
      GGA1 hinge peptide, which revealed that the two aromatic side chains of the WNSF
      sequence fit into a hydrophobic groove formed by aliphatic portions of the side
      chains of conserved arginine and lysine residues of GGA1-GAE, in a similar manner
      to the interaction between GGA-GAEs and acidic phenylalanine sequences from the
      accessory proteins. Fluorescence quenching experiments indicate that the GGA1
      hinge region binds to GGA1-GAE and competes with accessory proteins for binding.
      Taken together with the previous observation that gamma1 ear binds to the GGA1
      hinge region, the interaction between the hinge region and the GAE domain
      underlies the autoregulation of GGA function in clathrin-mediated trafficking
      through competing with the accessory proteins and the AP-1 complex.

PMID- 17506865
TI  - Human cardiovascular dose-response to supplemental oxygen.
AB  - AIM: The aim of the study was to examine the central and peripheral
      cardiovascular adaptation and its coupling during increasing levels of
      hyperoxaemia. We hypothesized a dose-related effect of hyperoxaemia on left
      ventricular performance and the vascular properties of the arterial tree.
      METHODS: Oscillometrically calibrated arterial subclavian pulse trace data were
      combined with echocardiographic recordings to obtain non-invasive estimates of
      left ventricular volumes, aortic root pressure and flow data. For complementary
      vascular parameters and control purposes whole-body impedance cardiography was
      applied. In nine (seven males) supine, resting healthy volunteers, aged 23-48
      years, data was collected after 15 min of air breathing and at increasing
      transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group,
      random order and blinded hyperoxemic protocol. RESULTS: Left ventricular stroke
      volume [86 +/- 13 to 75 +/- 9 mL (mean +/- SD)] and end-diastolic area (19.3 +/-
      4.4 to 16.8 +/- 4.3 cm(2)) declined (P < 0.05), and showed a linear, negative
      dose-response relationship to increasing arterial oxygen levels in a regression
      model. Peripheral resistance and characteristic impedance increased in a similar
      manner. Heart rate, left ventricular fractional area change, end-systolic area,
      mean arterial pressure, arterial compliance or carbon dioxide levels did not
      change. CONCLUSION: There is a linear dose-response relationship between arterial
      oxygen and cardiovascular parameters when the systemic oxygen tension increases
      above normal. A direct effect of supplemental oxygen on the vessels may therefore
      not be excluded. Proximal aortic and peripheral resistance increases from
      hyperoxaemia, but a decrease of venous return implies extra cardiac blood-pooling
      and compensatory relaxation of the capacitance vessels.

PMID- 17506866
TI  - Dynamic blood pressure control and middle cerebral artery mean blood velocity
      variability at rest and during exercise in humans.
AB  - AIMS: Cardiac failure and ischaemic heart disease patients receive standard of
      care cardiac beta(1)-adrenergic blockade medication. Such medication reduces
      cardiac output and cerebral blood flow. It is unknown whether the beta(1)
      adrenergic blockade-induced reduction of cardiac output in the presence of an
      exercise-induced reduction in cardiac-arterial baroreflex gain affects cerebral
      blood flow variability. This study evaluated the influence of cardiac output
      variability on beat-to-beat middle cerebral artery mean blood velocity (MCA
      V(mean)) during exercise with and without cardiac beta(1)-adrenergic blockade.
      METHODS: Eight men (22 +/- 1 years; mean +/- SE) performed 15 min bouts of
      moderate (105 +/- 11 W) and heavy (162 +/- 8 W) intensity cycling before and
      after cardio-selective beta(1)-adrenergic blockade (0.15 mg kg(-1) metoprolol).
      The relationship between changes in cardiac output or mean arterial pressure
      (MAP) and MCA V(mean) as well as cardiac-arterial baroreflex gain were evaluated
      using transfer function analysis. RESULTS: Both exercise intensities decreased
      the low frequency (LF) transfer function gain between cardiac output and MCA
      V(mean) (P < 0.05) with no significant influence of beta(1)-blockade. In
      contrast, the LF transfer function gain between MAP and MCA V(mean) remained
      stable also with no significant influence of metoprolol (P > 0.05). The LF
      transfer function gain between MAP and HR, an index of cardiac-arterial
      baroreflex gain, decreased from rest to heavy exercise with and without beta(1)
      blockade (P < 0.05). CONCLUSION: These findings suggest that the exercise
      intensity related reduction in cardiac-arterial baroreflex function at its
      operating point does not influence the dynamic control of MCA V(mean), even when
      the ability of exercise-induced increase in cardiac output is reduced by cardiac
      beta(1)-adrenergic blockade.

PMID- 17506867
TI  - Population pharmacokinetics-pharmacodynamics of alemtuzumab (Campath) in patients
      with chronic lymphocytic leukaemia and its link to treatment response.
AB  - AIMS: To characterize alemtuzumab pharmacokinetics and its exposure-response
      relationship with white blood cell (WBC) count in patients with B-cell chronic
      lymphocytic leukaemia (CLL). METHODS: Nonlinear mixed effects models were used to
      characterize plasma concentration-time data and WBC count-time data from 67
      patients. Logistic regression was used to relate summary measures of drug
      exposure to tumour response. RESULTS: Alemtuzumab pharmacokinetics were best
      characterized by a two-compartment model with nonlinear elimination where V(max)
      (microg h(-1)) was [1020 x (WBC count/10 x 10(9) l(-1))(0.194)], K(m) was 338
      microg l(-1), V(1) was 11.3 l, Q was 1.05 l h(-1) and V(2) was 41.5 l.
      Intersubject variability (ISV) in V(max), K(m), V(1) and V(2) was 32%, 145%, 84%
      and 179%, respectively. The reduction in WBC over time was modelled by a
      stimulatory loss indirect response model with values of 18.2 for E(max), 306
      microg l(-1) for EC(50), 1.56 x 10(9) cells l(-1) h(-1) for K(in) and 0.029 per h
      for K(out). The probability of achieving a complete or partial response was
      >/=50% when the maximal trough concentration exceeded 13.2 microg ml(-1) or when
      AUC(0-tau) exceeded 484 microg h(-1) ml(-1). CONCLUSIONS: Alemtuzumab displayed
      time- and concentration-dependent pharmacokinetics with large interpatient
      variability, both in pharmacokinetics and pharmacodynamics, which was probably
      reflective of differences in tumour burden among patients. A direct relationship
      between maximal trough concentrations and clinical outcomes was observed, with
      increasing alemtuzumab exposure resulting in a greater probability of positive
      tumour response.

PMID- 17506868
TI  - An investigation of the relationship between sex-steroid levels and urological
      symptoms: results from the Boston Area Community Health survey.
AB  - OBJECTIVES: To investigate whether circulating levels of sex hormones are
      associated with urological symptoms, using data from the Boston Area Community
      Health (BACH) Survey. SUBJECTS AND METHODS: BACH used a multistage stratified
      cluster approach to randomly sample 5506 adults aged 30-79 years in Boston, MA,
      USA. Anthropometric measures, lifestyle and psychosocial factors, comorbidities
      and urological symptoms were obtained using a questionnaire administered by an
      interviewer. Serum testosterone, sex hormone-binding globulin (SHBG),
      dehydroepiandrosterone sulphate (DHEAS), dihydrotestosterone (DHT) and oestradiol
      (E2) levels were measured, and bioavailable testosterone (BT) was calculated in
      1899 men (538 Black, 651 Hispanic and 710 White). Regression analysis was used to
      investigate the relationships between androgen levels and American Urological
      Association symptom index (AUA-SI), lower urinary tract symptoms (LUTS) (> or = 8
      on the AUA-SI), urinary incontinence (UI), dribble and hesitancy. RESULTS: Of all
      subjects, 19% reported LUTS, 6% UI, 9% dribble and 4% hesitancy. Testosterone, BT
      and DHEAS levels were inversely related to the AUA-SI (P = 0.009, <0.001 and
      <0.001, respectively); SHBG values and the AUA-SI were positively correlated (P <
      0.001). Adjusting for age, BT and DHEAS levels had negative relationships with
      the AUA-SI; BT and DHEAS levels were negatively related to LUTS and SHBG was
      positively related to LUTS (both P < 0.001); after age adjustment, only LUTS and
      DHEAS remained related, and only the relationship between dribble and E2 remained
      significant; no hormone levels were related to hesitancy. CONCLUSIONS:
      Circulating levels of sex hormones are generally not significant predictors of
      urological symptoms in men after adjusting for age. The pathophysiology of LUTS
      is complex and probably includes factors other than circulating sex steroid
      levels.

PMID- 17506869
TI  - Laparoscopic partial cystectomy for various bladder pathologies.
AB  - OBJECTIVE: To present our initial experience with laparoscopic partial cystectomy
      (LPC) in selected patients with various bladder pathologies. PATIENTS AND
      METHODS: Between December 2004 and April 2006, four patients had LPC at our
      centre (mean age 52 years, range 35-70); the transperitoneal approach was used
      for three and a pre-peritoneal approach for one. The surgical procedures used
      sequentially included transurethral incision around the lesion, laparoscopic
      excision of the lesion (partial cystectomy) and intracorporeal suturing.
      Laparoscopic pelvic lymphadenectomy was also used for the two patients with
      malignancy. RESULTS: All operations proceeded smoothly; the bladder pathologies
      included one bladder endometriosis, one bladder leiomyoma, one urothelial
      carcinoma within the bladder diverticulum and one urachal adenocarcinoma. The
      mean (range) operative duration was 197.5 (120-300) min, the estimated blood loss
      70 (50-100) mL, the hospital stay 6.75 (5-9) days, and duration of Foley
      catheterization 7.25 (6-9) days. No open conversion was required and no patient
      had peri-operative complications. The surgical margins were free of cancer and
      the dissected lymph nodes were negative in those two patients with bladder
      malignancy. CONCLUSIONS: LPC is safe and feasible in selected patients with
      various bladder pathologies.

PMID- 17506870
TI  - Emphysematous cystitis: a review of 135 cases.
AB  - OBJECTIVE: To review recently published data on emphysematous cystitis (EC), a
      potentially life-threatening condition characterized by air within the bladder
      wall, and that most typically affects middle-aged diabetic women. METHODS: All
      articles published in English between 1956 and 2006 were identified using a
      Medline search for keywords "emphysematous cystitis", and "cystitis
      emphysematosa." Epidemiological, clinical, diagnostic, pathological and
      therapeutic data were evaluated, including risk factors such as the presence of
      diabetes mellitus or other comorbid emphysematous infections of the urinary
      tract. RESULTS: In all, 102 published papers, including 135 cases of EC, were
      reviewed; the median patient age was 66 years, 64% were women and 67% had
      diabetes mellitus. Most cases were diagnosed using plain films of the abdomen
      (84%), although more recently, computed tomography was the primary imaging
      method. Escherichia coli was the most commonly isolated organism. Most patients
      were treated with medical management alone (90%), while 10% of infections were
      treated with a combination of medicine and surgery. The overall death rate was
      7%. CONCLUSIONS: EC is the most common and typically the least severe gas-forming
      infection of the urinary tract. Prompt diagnosis and treatment is warranted to
      prevent the potential morbidity and mortality of this infectious condition.

PMID- 17506871
TI  - Validation of the Pitts unified theory of prostate cancer, late-onset
      hypogonadism and carcinoma: the role of steroid 5alpha-reductase and steroid
      aromatase.

PMID- 17506872
TI  - Reducing one million child deaths from birth asphyxia--a survey of health systems
      gaps and priorities.
AB  - BACKGROUND: Millions of child deaths and stillbirths are attributable to birth
      asphyxia, yet limited information is available to guide policy and practice,
      particularly at the community level. We surveyed selected policymakers, programme
      implementers and researchers to compile insights on policies, programmes, and
      research to reduce asphyxia-related deaths. METHOD: A questionnaire was developed
      and pretested based on an extensive literature review, then sent by email (or
      airmail or fax, when necessary) to 453 policymakers, programme implementers, and
      researchers active in child health, particularly at the community level. The
      survey was available in French and English and employed 5-point scales for
      respondents to rate effectiveness and feasibility of interventions and
      indicators. Open-ended questions permitted respondents to furnish additional
      details based on their experience. Significance testing was carried out using chi
      square, F-test and Fisher's exact probability tests as appropriate. RESULTS: 173
      individuals from 32 countries responded (44%). National newborn survival policies
      were reported to exist in 20 of 27 (74%) developing countries represented, but
      respondents' answers were occasionally contradictory and revealed uncertainty
      about policy content, which may hinder policy implementation. Respondents
      emphasized confusing terminology and a lack of valid measurement indicators at
      community level as barriers to obtaining accurate data for decision making.
      Regarding interventions, birth preparedness and essential newborn care were
      considered both effective and feasible, while resuscitation at community level
      was considered less feasible. Respondents emphasized health systems strengthening
      for both supply and demand factors as programme priorities, particularly ensuring
      wide availability of skilled birth attendants, promotion of birth preparedness,
      and promotion of essential newborn care. Research priorities included
      operationalising birth preparedness, effectively evaluating pregnancy risk in the
      community, ensuring roles for traditional birth attendants (TBAs) that link them
      with the health system, testing the cost-effectiveness of various community
      cadres for resuscitation, and developing a clear case definition for case
      management and population monitoring. CONCLUSION: Without more attention to
      improve care and advance birth asphyxia research, the 2 million deaths related to
      asphyxia, plus associated maternal deaths, will remain out of reach of effective
      care, either skilled or community level, for many years to come.

PMID- 17506873
TI  - Effect of induction agent on vasopressor and steroid use, and outcome in patients
      with septic shock.
AB  - INTRODUCTION: In seriously ill patients, etomidate gives cardiovascular stability
      at induction of anaesthesia, but there is concern over possible adrenal
      suppression. Etomidate could reduce steroid synthesis and increase the need for
      vasopressor and steroid therapy. The outcome could be worse than in patients
      given other induction agents. METHODS: We reviewed 159 septic shock patients
      admitted to our intensive care unit (ICU) over a 40-month period to study the
      association between induction agent and clinical outcome, including vasopressor,
      inotrope, and steroid therapy. From our records, we retrieved induction agent
      use; vasopressor administration at induction; vasopressor, inotrope, and steroid
      administration in the ICU; and hospital outcome. RESULTS: Hospital mortality was
      65%. The numbers of patients given an induction agent were 74, etomidate; 25,
      propofol; 26, thiopental; 18, other agent; and 16, no agent. Vasopressor,
      inotrope, or steroid administration and outcome were not related to the induction
      agent chosen. Corticosteroid therapy given to patients who received etomidate did
      not affect outcome. Vasopressor therapy was required less frequently and in
      smaller doses when etomidate was used to induce anaesthesia. We found no evidence
      that either clinical outcome or therapy was affected when etomidate was used.
      Etomidate caused less cardiovascular depression than other induction agents in
      patients with septic shock. CONCLUSION: Etomidate use for critically ill patients
      should consider all of these issues and not simply the possibility of adrenal
      suppression, which may not be important when steroid supplements are used.

PMID- 17506874
TI  - The crystal structure of Escherichia coli TdcF, a member of the highly conserved
      YjgF/YER057c/UK114 family.
AB  - BACKGROUND: The YjgF/YER057c/UK114 family of proteins is widespread in nature,
      but has as yet no clearly defined biological role. Members of the family exist as
      homotrimers and are characterised by intersubunit clefts that are delineated by
      well-conserved residues; these sites are likely to be of functional significance,
      yet catalytic activity has never been detected for any member of this family. The
      gene encoding the TdcF protein of E. coli, a YjgF/YER057c/UK114 family member,
      resides in an operon that strongly suggests a role in the metabolism of 2
      ketobutyrate for this protein. RESULTS: We have determined the crystal structure
      of E. coli TdcF by molecular replacement to a maximum resolution of 1.6 A.
      Structures are also presented of TdcF complexed with a variety of ligands.
      CONCLUSION: The TdcF structure closely resembles those of all YjgF/YER057c/UK114
      family members determined thus far. It has the trimeric quaternary structure and
      intersubunit cavities characteristic of this family of proteins. We show that
      TdcF is capable of binding several low molecular weight metabolites bearing a
      carboxylate group, although the interaction with 2-ketobutyrate appears to be the
      most well defined. These observations may be indicative of a role for TdcF in
      sensing this potentially toxic metabolite.

PMID- 17506875
TI  - Exploring nervous system transcriptomes during embryogenesis and metamorphosis in
      Xenopus tropicalis using EST analysis.
AB  - BACKGROUND: The western African clawed frog Xenopus tropicalis is an anuran
      amphibian species now used as model in vertebrate comparative genomics. It
      provides the same advantages as Xenopus laevis but is diploid and has a smaller
      genome of 1.7 Gbp. Therefore X. tropicalis is more amenable to systematic
      transcriptome surveys. We initiated a large-scale partial cDNA sequencing project
      to provide a functional genomics resource on genes expressed in the nervous
      system during early embryogenesis and metamorphosis in X. tropicalis. RESULTS: A
      gene index was defined and analysed after the collection of over 48,785 high
      quality sequences. These partial cDNA sequences were obtained from an embryonic
      head and retina library (30,272 sequences) and from a metamorphic brain and
      spinal cord library (27,602 sequences). These ESTs are estimated to represent
      9,693 transcripts derived from an estimated 6,000 genes. Comparison of these cDNA
      sequences with protein databases indicates that 46% contain their start codon.
      Further annotation included Gene Ontology functional classification, InterPro
      domain analysis, alternative splicing and non-coding RNA identification. Gene
      expression profiles were derived from EST counts and used to define transcripts
      specific to metamorphic stages of development. Moreover, these ESTs allowed
      identification of a set of 225 polymorphic microsatellites that can be used as
      genetic markers. CONCLUSION: These cDNA sequences permit in silico cloning of
      numerous genes and will facilitate studies aimed at deciphering the roles of
      cognate genes expressed in the nervous system during neural development and
      metamorphosis. The genomic resources developed to study X. tropicalis biology
      will accelerate exploration of amphibian physiology and genetics. In particular,
      the model will facilitate analysis of key questions related to anuran
      embryogenesis and metamorphosis and its associated regulatory processes.

PMID- 17506876
TI  - Silencing of core transcription factors in human EC cells highlights the
      importance of autocrine FGF signaling for self-renewal.
AB  - BACKGROUND: Despite their distinct origins, human embryonic stem (hES) and
      embryonic carcinoma (hEC) cells share a number of similarities such as surface
      antigen expression, growth characteristics, the ability to either self-renew or
      differentiate, and control of the undifferentiated state by the same core
      transcription factors. To obtain further insights into the regulation of self
      renewal, we have silenced hES/hEC cell-specific genes in NCCIT hEC cells and
      analysed the downstream effects by means of microarrays. RESULTS: RNAi-mediated
      silencing of OCT4 and SOX2 induced differentiation with mesodermal
      characteristics. Markers of trophoblast induction were only transiently up
      regulated in the OCT4 knock-down. Independent knock-downs of NANOG produced a
      proliferation rather than a differentiation phenotype, which may be due to high
      NANOG expression levels in the cell line used. Published ChIP-chip data from hES
      cells were used to identify putative direct targets. RNAi-mediated
      differentiation was accompanied by direct down-regulation of known hES/hEC cell
      markers. This included all three core transcription factors in the case of the
      OCT4 and SOX2 knock-downs, confirming previous findings of reciprocal activation
      in ES cells. Furthermore, large numbers of histone genes as well as epigenetic
      regulators were differentially expressed, pointing at chromatin remodeling as an
      additional regulatory level in the differentiation process. Moreover, loss of
      self-renewal was accompanied by the down-regulation of genes involved in FGF
      signaling. FGF receptor inhibition for short and prolonged periods of time
      revealed that the ERK/MAPK cascade is activated by endogenously expressed
      fibroblast growth factors and that FGF signaling is cruicial for maintaining the
      undifferentiated state of hEC cells, like in hES cells. CONCLUSION: Control of
      self-renewal appears to be very similar in hEC and hES cells. This is supported
      by large numbers of common transcription factor targets and the requirement for
      autocrine FGF signaling.

PMID- 17506877
TI  - Analysis of gene expression in cotton fiber initials.
AB  - BACKGROUND: Cotton (Gossypium hirsutum L.) fibers are trichomes that initiate
      from the ovule epidermis. Little is known about the developmental pathway causing
      fiber to differentiate from ovular epidermal cells even though limits on the
      number of cells that differentiate into fiber will limit yield. RESULTS: A method
      was developed to isolate RNA from fiber initials 1 day post anthesis (dpa).
      Complementary DNA libraries representing 1 dpa fibers and other cotton tissues
      were sequenced and analyzed. Assembly of G. hirsutum Expressed Sequenced Tags
      (ESTs) identified over 11,000 sequences not previously represented in GenBank.
      New genes identified among these ESTs were represented on microarrays. The
      microarrays were used to identify genes enriched in fiber initials (1 dpa fibers)
      and elongating fibers. Analyses of Gene Ontologies (GO) of differentially
      expressed genes determined that terms associated with the "membranes" were
      statistically over represented among genes increased in expression in fiber
      initials and 10 dpa fibers. Staining ovules with a fluorescent dye confirmed an
      increase in Endoplasmic Reticulum (ER) occurred in fiber initials on the day of
      anthesis, persisted through 3 dpa and was absent in a fiberless mutant. Two genes
      similar to the CAPRICE/TRIPTYCHON (CPC) gene that inhibits differentiation of
      leaf trichomes in Arabidopsis were also characterized. Genes associated with
      novel regulation of brassinosterols, GTP mediated signal transduction and cell
      cycle control and components of a Ca+2 mediated signaling pathway were
      identified. Staining of cellular Ca+2 indicated that fiber initials had more Ca+2
      than other ovule cells supporting a role for Ca+2 in fiber development.
      CONCLUSION: Analysis of genes expressed in fiber initials identified a unique
      stage in fiber development characterized by an increase in ER and Ca+2 levels
      that occurred between 0 and 1 dpa. The gene similar to CPC has a MYB domain but
      appears to lack a transcription activating domain similar to the Arabisopsis
      gene. The method used to stain the ER also can be used to count fiber initials
      and showed fiber cells develop from adjacent cells unlike leaf trichomes.

PMID- 17506878
TI  - Characteristics of communication guidelines that facilitate or impede guideline
      use: a focus group study.
AB  - BACKGROUND: The quality of doctor-patient communication has a major impact on the
      quality of medical care. Communication guidelines define best practices for
      doctor patient communication and are therefore an important tool for improving
      communication. However, adherence to communication guidelines remains low,
      despite doctors participating in intensive communication skill training.
      Implementation research shows that adherence is higher for guidelines in general
      that are user centred and feasible, which implies that they are consistent with
      users' opinions, tap into users' existing skills and fit into existing routines.
      Developers of communication guidelines seem to have been somewhat negligent with
      regard to user preferences and guideline feasibility. In order to promote the
      development of user centred and practicable communication guidelines, we elicited
      user preferences and identified which guideline characteristics facilitate or
      impede guideline use. METHODS: Seven focus group interviews were conducted with
      experienced GPs, communication trainers (GPs and behavioural scientists) and
      communication learners (GP trainees and medical students) and three focus group
      interviews with groups of GP trainees only. All interviews were transcribed and
      analysed qualitatively. RESULTS: The participants identified more impeding
      guideline characteristics than facilitating ones. The most important impeding
      characteristic was that guidelines do not easily fit into GPs' day-to-day
      practice. This is due to rigidity and inefficiency of communication guidelines
      and erroneous assumptions underpinning guideline development. The most important
      facilitating characteristic was guideline structure. Guidelines that were
      structured in distinct phases helped users to remain in control of consultations,
      which was especially useful in complicated consultations. CONCLUSION: Although
      communication guidelines are generally considered useful, especially for
      structuring consultations, their usefulness is impaired by lack of flexibility
      and applicability to practice routines. User centred and feasible guidelines
      should combine the advantages of helping doctors to structure consultations with
      flexibility to tailor communication strategies to specific contexts and
      situations.

PMID- 17506880
TI  - Prevalence, intensity and extent of Oral Impacts on Daily Performances associated
      with self-perceived malocclusion in 11-12-year-old children.
AB  - BACKGROUND: To determine the prevalence, intensity and extent of the Oral Impacts
      on Daily Performances associated with self-perceived malocclusion among Peruvian
      schoolchildren. METHODS: Eight hundred and five children aged 11 to 12 years
      attending 4 of 7 randomly selected schools linked to a Health Centre in Lima,
      Peru, participated in the study. The Spanish (Peru)Child-OIDP was used to assess
      the prevalence, intensity and extent of oral impacts on 8 daily performances
      (eating, speaking, teeth cleaning, sleeping, smiling, studying, emotion and
      social contact). Self-perceived malocclusion included complaints about position
      of teeth, spacing of teeth and deformity of mouth or face. The prevalence of oral
      impacts was compared by covariables using the Chi-square test, whereas the
      intensity and extent of oral impacts were compared by covariables through the
      Mann-Whitney test. RESULTS: Only 15.5% of children reported impacts associated
      with self-perceived malocclusion during the last 3 months. Of them, 18.4%
      reported impacts of severe or very severe intensity and 76.0% reported impacts on
      only one daily performance. Psychosocial activities such as smiling, emotion and
      social contact were the most frequently and severely impacted everyday
      activities. CONCLUSION: Impacts of self-perceived malocclusion primarily affected
      psychological and social everyday activities. These findings provide further
      evidence to support the importance of psychological and social components of oral
      health on children's lives.

PMID- 17506879
TI  - The association of self-esteem, depression and body satisfaction with obesity
      among Turkish adolescents.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence of
      overweight and obesity and to examine the effects of actual weight status,
      perceived weight status and body satisfaction on self-esteem and depression in a
      high school population in Turkey. METHODS: A cross-sectional survey of 2101 tenth
      grade Turkish adolescents aged 15-18 was conducted. Body mass index (BMI) was
      calculated using weight and height measures. The overweight and obesity were
      based on the age- and gender-specific BMI cut-off points of the International
      Obesity Task Force values. Self-esteem was measured using the Rosenberg Self
      Esteem Scale, and depression was measured using Children's Depression Inventory.
      Logistic regression analysis was used to examine relationships among the
      variables. RESULTS: Based on BMI cut-off points, 9.0% of the students were
      overweight and 1.1% were obese. Logistic regression analysis indicated that (1)
      being male and being from a higher socio-economical level were important in the
      prediction of overweight based on BMI; (2) being female and being from a higher
      socio-economical level were important in the prediction of perceived overweight;
      (3) being female was important in the prediction of body dissatisfaction; (4)
      body dissatisfaction was related to low self-esteem and depression, perceived
      overweight was related only to low self-esteem but actual overweight was not
      related to low self-esteem and depression in adolescents. CONCLUSION: The results
      of this study suggest that school-based adolescents in urban Turkey have a lower
      risk of overweight and obesity than adolescents in developed countries. The
      findings of this study suggest that psychological well-being of adolescents is
      more related to body satisfaction than actual and perceived weight status is.

PMID- 17506881
TI  - Paracheck-Pf accuracy and recently treated Plasmodium falciparum infections: is
      there a risk of over-diagnosis?
AB  - BACKGROUND: An assessment of the accuracy of Paracheck Pf, a malaria rapid
      diagnostic test (RDT) detecting histidine rich protein 2 was undertaken amongst
      children aged 6-59 months in eastern Democratic Republic of Congo. METHODS: This
      RDT assessment occurred in conjunction with an ACT efficacy trial. Febrile
      children were simultaneously screened with both RDT and high quality microscopy
      and those meeting inclusion criteria were followed for 35 days. RESULTS: 358
      febrile children were screened with 180 children recruited for five weeks follow
      up. On screening, the RDT accurately diagnosed all 235 true malaria cases,
      indicating 100% RDT sensitivity. Of the 123 negative slides, the RDT gave 59
      false-positive results, indicating 52.0% (64/123) RDT specificity. During follow
      up after treatment with an artemisinin-based combination therapy, 98.2%
      (110/112), 94.6% (106/112), 92.0% (103/112) and 73.5% (50/68) of effectively
      treated children were still false-positive by RDT at days 14, 21, 28 and 35,
      respectively. CONCLUSION: Results show that though the use of Paracheck-Pf is as
      sensitive as microscopy in detecting true malaria cases, a low specificity did
      present a high frequency of false-positive RDT results. What's more, a duration
      of RDT false-positivity was found that significantly surpassed the 'fortnight'
      after effective treatment reported by its manufacturer. Though further research
      is needed in assessing RDT accuracy, study results showing the presence of
      frequent false positivity should be taken into consideration to avoid clinicians
      inappropriately focusing on malaria, not identifying the true cause of illness,
      and providing unnecessary treatment.

PMID- 17506882
TI  - Experimental and analytical validation of a modular acetabular prosthesis in
      total hip arthroplasty.
AB  - A finite element model has been developed to predict in vivo micro motion between
      a modular acetabular cup and liner after cement less total hip arthroplasty. The
      purpose of this study is to experimentally validate the model. Six LVDT sensors
      were used to monitor the micromotion of the liner when subjected to loading
      conditions ranging from 250 N to 5000 N. Deformations at points of interest for
      both the experiment and FEM were compared. Results of the FEM with different
      coefficient of friction between the liner and the cup were investigated to
      correlate with the experimental results.

PMID- 17506883
TI  - The Deuterator: software for the determination of backbone amide deuterium levels
      from H/D exchange MS data.
AB  - BACKGROUND: The combination of mass spectrometry and solution phase amide
      hydrogen/deuterium exchange (H/D exchange) experiments is an effective method for
      characterizing protein dynamics, and protein-protein or protein-ligand
      interactions. Despite methodological advancements and improvements in
      instrumentation and automation, data analysis and display remains a tedious
      process. The factors that contribute to this bottleneck are the large number of
      data points produced in a typical experiment, each requiring manual curation and
      validation, and then calculation of the level of backbone amide exchange. Tools
      have become available that address some of these issues, but lack sufficient
      integration, functionality, and accessibility required to address the needs of
      the H/D exchange community. To date there is no software for the analysis of H/D
      exchange data that comprehensively addresses these issues. RESULTS: We have
      developed an integrated software system for the automated analysis and
      representation of H/D exchange data that has been titled "The Deuterator". Novel
      approaches have been implemented that enable high throughput analysis, automated
      determination of deuterium incorporation, and deconvolution of overlapping
      peptides. This has been achieved by using methods involving iterative theoretical
      envelope fitting, and consideration of peak data within expected m/z ranges.
      Existing common file formats have been leveraged to allow compatibility with the
      output from the myriad of MS instrument platforms and peptide sequence database
      search engines.A web-based interface is used to integrate the components of The
      Deuterator that are able to analyze and present mass spectral data from
      instruments with varying resolving powers. The results, if necessary, can then be
      confirmed, adjusted, re-calculated and saved. Additional tools synchronize the
      curated calculation parameters with replicate time points, increasing throughput.
      Saved results can then be used to plot deuterium buildup curves and 3D structural
      overlays. The system has been used successfully in a production environment for
      over one year and is freely available as a web tool at the project home page
      http://deuterator.florida.scripps.edu. CONCLUSION: The automated calculation and
      presentation of H/D exchange data in a user interface enables scientists to
      organize and analyze data efficiently. Integration of the different components of
      The Deuterator coupled with the flexibility of common data file formats allow
      this system to be accessible to the broadening H/D exchange community.

PMID- 17506884
TI  - Metallic foreign body in middle ear: an unusual cause of hearing loss.
AB  - This is a rare case report of a foreign metallic body found in the middle ear.
      During the use of an electric welding by a metalworker, a glowing drop of
      dissolved metal overrun, burning the skin of his external auditory meatus,
      perforated the tympanic membrane and finally was implanted around the ossicles as
      a foreign body. Due to difficulty of the physical examination and the moderate
      symptoms (hearing loss and sense of fullness), the foreign body was detected six
      months after the incident, by CT scanning and it was removed by a transcanal
      approach under general anesthesia. A successful ossiculoplasty-tympanoplasty was
      followed four weeks later.

PMID- 17506885
TI  - Discriminators of mouse bladder response to intravesical Bacillus Calmette-Guerin
      (BCG).
AB  - BACKGROUND: Intravesical Bacillus Calmette-Guerin (BCG) is an effective treatment
      for bladder superficial carcinoma and it is being tested in interstitial cystitis
      patients, but its precise mechanism of action remains poorly understood. It is
      not clear whether BCG induces the release of a unique set of cytokines apart from
      its pro-inflammatory effects. Therefore, we quantified bladder inflammatory
      responses and alterations in urinary cytokine protein induced by intravesical BCG
      and compared the results to non-specific pro-inflammatory stimuli (LPS and TNF
      alpha). We went further to determine whether BCG treatment alters cytokine gene
      expression in the urinary bladder. METHODS: C57BL/6 female mice received four
      weekly instillations of BCG, LPS, or TNF-alpha. Morphometric analyses were
      conducted in bladders isolated from all groups and urine was collected for
      multiplex analysis of 18 cytokines. In addition, chromatin immune precipitation
      combined with real-time polymerase chain reaction assay (CHIP/Q-PCR) was used to
      test whether intravesical BCG would alter bladder cytokine gene expression.
      RESULTS: Acute BCG instillation induced edema which was progressively replaced by
      an inflammatory infiltrate, composed primarily of neutrophils, in response to
      weekly administrations. Our morphological analysis suggests that these
      polymorphonuclear neutrophils are of prime importance for the bladder responses
      to BCG. Overall, the inflammation induced by BCG was higher than LPS or TNF-alpha
      treatment but the major difference observed was the unique granuloma formation in
      response to BCG. Among the cytokines measured, this study highlighted the
      importance of IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-10, IL-17, GM-CSF, KC, and
      Rantes as discriminators between generalized inflammation and BCG-specific
      inflammatory responses. CHIP/Q-PCR indicates that acute BCG instillation induced
      an up-regulation of IL-17A, IL-17B, and IL-17RA, whereas chronic BCG induced IL
      17B, IL-17RA, and IL-17RB. CONCLUSION: To the best of our knowledge, the present
      work is the first to report that BCG induces an increase in the IL-17 family
      genes. In addition, BCG induces a unique type of persisting bladder inflammation
      different from TNF-alpha, LPS, and, most likely, other classical pro-inflammatory
      stimuli.

PMID- 17506886
TI  - Regulatory conservation of protein coding and microRNA genes in vertebrates:
      lessons from the opossum genome.
AB  - BACKGROUND: Being the first noneutherian mammal sequenced, Monodelphis domestica
      (opossum) offers great potential for enhancing our understanding of the
      evolutionary processes that take place in mammals. This study focuses on the
      evolutionary relationships between conservation of noncoding sequences, cis
      regulatory elements, and biologic functions of regulated genes in opossum and
      eight vertebrate species. RESULTS: Analysis of 145 intergenic microRNA and all
      protein coding genes revealed that the upstream sequences of the former are up to
      twice as conserved as the latter among mammals, except in the first 500 base
      pairs, where the conservation is similar. Comparison of promoter conservation in
      513 protein coding genes and related transcription factor binding sites (TFBSs)
      showed that 41% of the known human TFBSs are located in the 6.7% of promoter
      regions that are conserved between human and opossum. Some core biologic
      processes exhibited significantly fewer conserved TFBSs in human-opossum
      comparisons, suggesting greater functional divergence. A new measure of
      efficiency in multigenome phylogenetic footprinting (base regulatory potential
      rate [BRPR]) shows that including human-opossum conservation increases
      specificity in finding human TFBSs. CONCLUSION: Opossum facilitates better
      estimation of promoter conservation and TFBS turnover among mammals. The fact
      that substantial TFBS numbers are located in a small proportion of the human
      opossum conserved sequences emphasizes the importance of marsupial genomes for
      phylogenetic footprinting-based motif discovery strategies. The BRPR measure is
      expected to help select genome combinations for optimal performance of these
      algorithms. Finally, although the etiology of the microRNA upstream increased
      conservation remains unknown, it is expected to have strong implications for our
      understanding of regulation of their expression.

PMID- 17506887
TI  - Prevalence of maternal smoking and environmental tobacco smoke exposure during
      pregnancy and impact on birth weight: retrospective study using Millennium
      Cohort.
AB  - BACKGROUND: Meta-analyses of studies investigating the impact of maternal
      environmental tobacco smoke (ETS) on birth weight have not produced robust
      findings. Although, ante natal ETS exposure probably reduces infant's birth
      weights, the scale of this exposure remains unknown. We conducted a large, cohort
      study to assess the impact of ETS exposure on birth weight whilst adjusting for
      the many factors known to influence this. METHOD: Retrospective study using
      interview data from parents of 18,297 children born in 2000/2001 and living in
      the UK 9 months afterwards (the Millennium Cohort Survey). Comparison of birth
      weight, sex and gestational age specific (SGA) z score, birth before 37 weeks and
      birth weight < 2.5 Kg (LBW) in infants born to women exposed to: i) no tobacco
      smoke, ii) ETS only and iii) maternal smoking whilst pregnant. RESULTS: 13% of UK
      infants were exposed to ETS and 36% to maternal smoking ante natally. Compared to
      no ante natal tobacco smoke exposure, domestic ETS lowered infants' adjusted mean
      birth weights by 36 g (95% CI, 5 g to 67 g) and this effect showed a dose
      response relationship. ETS exposure also caused non-significant increases in the
      adjusted risks of Low Birth Weight (<2.5 Kg) [OR 1.23 (95% CI, 0.96 to 1.58) and
      premature birth [OR 1.21 (95% CI, 0.96 to 1.51)], whilst the impacts of maternal
      smoking were greater and statistically significant. CONCLUSION: UK prevalences of
      domestic ETS exposure and maternal smoking in pregnancy remain high and ETS
      exposure lowers infants' birth weights.

PMID- 17506888
TI  - Phylogenetic analysis of condensation domains in NRPS sheds light on their
      functional evolution.
AB  - BACKGROUND: Non-ribosomal peptide synthetases (NRPSs) are large multimodular
      enzymes that synthesize a wide range of biologically active natural peptide
      compounds, of which many are pharmacologically important. Peptide bond formation
      is catalyzed by the Condensation (C) domain. Various functional subtypes of the C
      domain exist: An LCL domain catalyzes a peptide bond between two L-amino acids, a
      DCL domain links an L-amino acid to a growing peptide ending with a D-amino acid,
      a Starter C domain (first denominated and classified as a separate subtype here)
      acylates the first amino acid with a beta-hydroxy-carboxylic acid (typically a
      beta-hydroxyl fatty acid), and Heterocyclization (Cyc) domains catalyze both
      peptide bond formation and subsequent cyclization of cysteine, serine or
      threonine residues. The homologous Epimerization (E) domain flips the chirality
      of the last amino acid in the growing peptide; Dual E/C domains catalyze both
      epimerization and condensation. RESULTS: In this paper, we report on the
      reconstruction of the phylogenetic relationship of NRPS C domain subtypes and
      analyze in detail the sequence motifs of recently discovered subtypes (Dual E/C,
      DCL and Starter domains) and their characteristic sequence differences, mutually
      and in comparison with LCL domains. Based on their phylogeny and the comparison
      of their sequence motifs, LCL and Starter domains appear to be more closely
      related to each other than to other subtypes, though pronounced differences in
      some segments of the protein account for the unequal donor substrates (amino vs.
      beta-hydroxy-carboxylic acid). Furthermore, on the basis of phylogeny and the
      comparison of sequence motifs, we conclude that Dual E/C and DCL domains share a
      common ancestor. In the same way, the evolutionary origin of a C domain of
      unknown function in glycopeptide (GP) NRPSs can be determined to be an LCL
      domain. In the case of two GP C domains which are most similar to DCL but which
      have LCL activity, we postulate convergent evolution. CONCLUSION: We systematize
      all C domain subtypes including the novel Starter C domain. With our results, it
      will be easier to decide the subtype of unknown C domains as we provide profile
      Hidden Markov Models (pHMMs) for the sequence motifs as well as for the entire
      sequences. The determined specificity conferring positions will be helpful for
      the mutation of one subtype into another, e.g. turning DCL to LCL, which can be a
      useful step for obtaining novel products.

PMID- 17506890
TI  - A mechanism for the sharp transition of morphogen gradient interpretation in
      Xenopus.
AB  - BACKGROUND: One way in which positional information is established during
      embryonic development is through the graded distribution of diffusible
      morphogens. Unfortunately, little is known about how cells interpret different
      concentrations of morphogen to activate different genes or how thresholds are
      generated in a morphogen gradient. RESULTS: Here we show that the concentration
      dependent induction of the T-box transcription factor Brachyury (Xbra) and the
      homeobox-containing gene Goosecoid (Gsc) by activin in Xenopus can be explained
      by the dynamics of a simple network consisting of three elements with a mutual
      negative feedback motif that can function to convert a graded signal (activin)
      into a binary output (Xbra on and Gsc off, or vice versa). Importantly, such a
      system can display sharp thresholds. Consistent with the predictions of our
      model, Xenopus ectodermal cells display a binary response at the single cell
      level after treatment with activin. CONCLUSION: This kind of simple network with
      mutual negative feedback might provide a general mechanism for selective gene
      activation in response to different levels of a single external signal. It
      provides a mechanism by which a sharp boundary might be created between domains
      of different cell types in response to a morphogen gradient.

PMID- 17506889
TI  - A global view of gene expression in lithium and zinc treated sea urchin embryos:
      new components of gene regulatory networks.
AB  - BACKGROUND: The genome of the sea urchin Strongylocentrotus purpuratus has
      recently been sequenced because it is a major model system for the study of gene
      regulatory networks. Embryonic expression patterns for most genes are unknown,
      however. RESULTS: Using large-scale screens on arrays carrying 50% to 70% of all
      genes, we identified novel territory-specific markers. Our strategy was based on
      computational selection of genes that are differentially expressed in lithium
      treated embryos, which form excess endomesoderm, and in zinc-treated embryos, in
      which endomesoderm specification is blocked. Whole-mount in situ hybridization
      (WISH) analysis of 700 genes indicates that the apical organ region is eliminated
      in lithium-treated embryos. Conversely, apical and specifically neural markers
      are expressed more broadly in zinc-treated embryos, whereas endomesoderm
      signaling is severely reduced. Strikingly, the number of serotonergic neurons is
      amplified by at least tenfold in zinc-treated embryos. WISH analysis further
      indicates that there is crosstalk between the Wnt (wingless int), Notch, and
      fibroblast growth factor signaling pathways in secondary mesoderm cell
      specification and differentiation, similar to signaling cascades that function
      during development of presomitic mesoderm in mouse embryogenesis. We provide
      differential expression data for more than 4,000 genes and WISH patterns of more
      than 250 genes, and more than 2,400 annotated WISH images. CONCLUSION: Our work
      provides tissue-specific expression patterns for a large fraction of the sea
      urchin genes that have not yet been included in existing regulatory networks and
      await functional integration. Furthermore, we noted neuron-inducing activity of
      zinc on embryonic development; this is the first observation of such activity in
      any organism.

PMID- 17506891
TI  - Novel subdomains of the mouse olfactory bulb defined by molecular heterogeneity
      in the nascent external plexiform and glomerular layers.
AB  - BACKGROUND: In the mouse olfactory system, the role of the olfactory bulb in
      guiding olfactory sensory neuron (OSN) axons to their targets is poorly
      understood. What cell types within the bulb are necessary for targeting is
      unknown. What genes are important for this process is also unknown. Although
      projection neurons are not required, other cell-types within the external
      plexiform and glomerular layers also form synapses with OSNs. We hypothesized
      that these cells are important for targeting, and express spatially
      differentially expressed guidance cues that act to guide OSN axons within the
      bulb. RESULTS: We used laser microdissection and microarray analysis to find
      genes that are differentially expressed along the dorsal-ventral, medial-lateral,
      and anterior-posterior axes of the bulb. The expression patterns of these genes
      divide the bulb into previously unrecognized subdomains. Interestingly, some
      genes are expressed in both the medial and lateral bulb, showing for the first
      time the existence of symmetric expression along this axis. We use a regeneration
      paradigm to show that several of these genes are altered in expression in
      response to deafferentation, consistent with the interpretation that they are
      expressed in cells that interact with OSNs. CONCLUSION: We demonstrate that the
      nascent external plexiform and glomerular layers of the bulb can be divided into
      multiple domains based on the expression of these genes, several of which are
      known to function in axon guidance, synaptogenesis, and angiogenesis. These genes
      represent candidate guidance cues that may act to guide OSN axons within the bulb
      during targeting.

PMID- 17506892
TI  - Latent profile analysis in frontotemporal lobar degeneration and related
      disorders: clinical presentation and SPECT functional correlates.
AB  - BACKGROUND: Frontotemporal Lobar Degeneration (FTLD) thus recently renamed,
      refers to a spectrum of heterogeneous conditions. This same heterogeneity of
      presentation represents the major methodological limit for the correct evaluation
      of clinical designation and brain functional correlates. At present, no study has
      investigated clinical clusters due to specific cognitive and behavioural
      disturbances beyond current clinical criteria. The aim of this study was to
      identify clinical FTLD presentation, based on cognitive and behavioural profile,
      and to define their SPECT functional correlations. METHODS: Ninety-seven FTLD
      patients entered the study. A clinical evaluation and standardised assessment
      were preformed, as well as a brain SPECT perfusion imaging study. Latent Profile
      Analysis on clinical, neuropsychological, and behavioural data was performed.
      Voxel-basis analysis of SPECT data was computed. RESULTS: Three specific clusters
      were identified and named "pseudomanic behaviour" (LC1), "cognitive" (LC2), and
      "pseudodepressed behaviour" (LC3) endophenotypes. These endophenotypes showed a
      comparable hypoperfusion in left temporal lobe, but a specific pattern involving:
      medial and orbitobasal frontal cortex in LC1, subcortical brain region in LC2,
      and right dorsolateral frontal cortex and insula in LC3. CONCLUSION: These
      findings provide evidence that specific functional-cluster symptom relationship
      can be delineated in FTLD patients by a standardised assessment. The
      understanding of the different functional correlates of clinical presentations
      will hopefully lead to the possibility of individuating diagnostic and treatment
      algorithms.

PMID- 17506893
TI  - CAM therapies among primary care patients using opioid therapy for chronic pain.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is an increasingly
      common therapy used to treat chronic pain syndromes. However; there is limited
      information on the utilization and efficacy of CAM therapy in primary care
      patients receiving long-term opioid therapy. METHOD: A survey of CAM therapy was
      conducted with a systematic sample of 908 primary care patients receiving opioids
      as a primary treatment method for chronic pain. Subjects completed a
      questionnaire designed to assess utilization, efficacy and costs of CAM therapies
      in this population. RESULTS: Patients were treated for a variety of pain problems
      including low back pain (38.4%), headaches (9.9%), and knee pain (6.5%); the
      average duration of pain was 16 years. The median morphine equivalent opioid dose
      was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample
      reported CAM therapy use in the past 12 months. Therapies utilized included
      massage therapy (27.3%, n = 248), chiropractic treatment (17.8%, n = 162),
      acupuncture (7.6%, n = 69), yoga (6.1%, n = 55), herbs and supplements (6.8%, n =
      62), and prolotherapy (5.9%, n = 54). CAM utilization was significantly related
      to age female gender, pain severity income pain diagnosis of neck and upper back
      pain, and illicit drug use. Medical insurance covered chiropractic treatment
      (81.8%) and prolotherapy (87.7%), whereas patients primarily paid for other CAM
      therapies. Over half the sample reported that one or more of the CAM therapies
      were helpful. CONCLUSION: This study suggests CAM therapy is widely used by
      patients receiving opioids for chronic pain. Whether opioids can be reduced by
      introducing such therapies remains to be studied.

PMID- 17506894
TI  - Transcriptome analysis of the venom gland of the Mexican scorpion Hadrurus
      gertschi (Arachnida: Scorpiones).
AB  - BACKGROUND: Scorpions like other venomous animals possess a highly specialized
      organ that produces, secretes and disposes the venom components. In these
      animals, the last postabdominal segment, named telson, contains a pair of
      venomous glands connected to the stinger. The isolation of numerous scorpion
      toxins, along with cDNA-based gene cloning and, more recently, proteomic analyses
      have provided us with a large collection of venom components sequences. However,
      all of them are secreted, or at least are predicted to be secretable gene
      products. Therefore very little is known about the cellular processes that
      normally take place inside the glands for production of the venom mixture. To
      gain insights into the scorpion venom gland biology, we have decided to perform a
      transcriptomic analysis by constructing a cDNA library and conducting a random
      sequencing screening of the transcripts. RESULTS: From the cDNA library prepared
      from a single venom gland of the scorpion Hadrurus gertschi, 160 expressed
      sequence tags (ESTs) were analyzed. These transcripts were further clustered into
      68 unique sequences (20 contigs and 48 singlets), with an average length of 919
      bp. Half of the ESTs can be confidentially assigned as homologues of annotated
      gene products. Annotation of these ESTs, with the aid of Gene Ontology terms and
      homology to eukaryotic orthologous groups, reveals some cellular processes
      important for venom gland function; including high protein synthesis, tuned
      posttranslational processing and trafficking. Nonetheless, the main group of the
      identified gene products includes ESTs similar to known scorpion toxins or other
      previously characterized scorpion venom components, which account for nearly 60%
      of the identified proteins. CONCLUSION: To the best of our knowledge this report
      contains the first transcriptome analysis of genes transcribed by the venomous
      gland of a scorpion. The data were obtained for the species Hadrurus gertschi,
      belonging to the family Caraboctonidae. One hundred and sixty ESTs were analyzed,
      showing enrichment in genes that encode for products similar to known venom
      components, but also provides the first sketch of cellular components, molecular
      functions, biological processes and some unique sequences of the scorpion venom
      gland.

PMID- 17506895
TI  - A non-sense mutation in the putative anti-mutator gene ada/alkA of Mycobacterium
      tuberculosis and M. bovis isolates suggests convergent evolution.
AB  - BACKGROUND: Previous studies have suggested that variations in DNA repair genes
      of W-Beijing strains may have led to transient mutator phenotypes which in turn
      may have contributed to host adaptation of this strain family. Single nucleotide
      polymorphism (SNP) in the DNA repair gene mutT1 was identified in MDR-prone
      strains from the Central African Republic. A Mycobacteriumtuberculosis H37Rv
      mutant inactivated in two DNA repair genes, namely ada/alkA and ogt, was shown to
      display a hypermutator phenotype. We then looked for polymorphisms in these genes
      in Central African Republic strains (CAR). RESULTS: In this study, 55 MDR and 194
      non-MDR strains were analyzed. Variations in DNA repair genes ada/alkA and ogt
      were identified. Among them, by comparison to M. tuberculosis published
      sequences, we found a non-sense variation in ada/alkA gene which was also
      observed in M. bovis AF2122 strain. SNPs that are present in the adjacent regions
      to the amber variation are different in M. bovis and in M. tuberculosis strain.
      CONCLUSION: An Amber codon was found in the ada/alkA locus of clustered M.
      tuberculosis isolates and in M. bovis strain AF2122. This is likely due to
      convergent evolution because SNP differences between strains are incompatible
      with horizontal transfer of an entire gene. This suggests that such a variation
      may confer a selective advantage and be implicated in hypermutator phenotype
      expression, which in turn contributes to adaptation to environmental changes.

PMID- 17506897
TI  - Urmia Lake (Northwest Iran): a brief review.
AB  - Lake Urmia (or Ormiyeh) is one of the largest hypersaline lakes in the world and
      the habitat of a unique bisexual Artemia species (A. urmiana). Despite this, and
      several other values of the lake, little literature on it has been published. The
      present paper is an attempt to provide a brief review on various aspects of the
      lake. Urmia Lake, located in northwestern Iran, is an oligotrophic lake of
      thalassohaline origin with a total surface area between 4750 and 6100 km2 and a
      maximum depth of 16 m at an altitude of 1250 m. The lake is divided into north
      and south parts separated by a causeway in which a 1500-m gap provides little
      exchange of water between the two parts. Due to drought and increased demands for
      agricultural water in the lake's basin, the salinity of the lake has risen to
      more than 300 g/L during recent years, and large areas of the lake bed have been
      desiccated. Therefore, management and conservation of this incomparable ecosystem
      should be considered to improve the current condition by fisheries research
      institutes.

PMID- 17506896
TI  - Germinal center architecture disturbance during Plasmodium berghei ANKA infection
      in CBA mice.
AB  - BACKGROUND: Immune responses to malaria blood stage infection are in general
      defective, with the need for long-term exposure to the parasite to achieve
      immunity, and with the development of immunopathology states such as cerebral
      malaria in many cases. One of the potential reasons for the difficulty in
      developing protective immunity is the poor development of memory responses. In
      this paper, the potential association of cellular reactivity in lymphoid organs
      (spleen, lymph nodes and Peyer's patches) with immunity and pathology was
      evaluated during Plasmodium berghei ANKA infection in CBA mice. METHODS: CBA mice
      were infected with 1 x 10(6) P. berghei ANKA-parasitized erythrocytes and killed
      on days 3, 6-8 and 10 of infection. The spleen, lymph nodes and Peyer's patches
      were collected, fixed in Carson's formalin, cut in 5 mum sections, mounted in
      glass slides, stained with Lennert's Giemsa and haematoxylin-eosin and analysed
      with bright-field microscopy. RESULTS: Early (day 3) strong activation of T cells
      in secondary lymphoid organs was observed and, on days 6-8 of infection, there
      was overwhelming activation of B cells, with loss of conventional germinal center
      architecture, intense centroblast activation, proliferation and apoptosis but
      little differentiation to centrocytes. In the spleen, the marginal zone
      disappeared and the limits between the disorganized germinal center and the red
      pulp were blurred. Intense plasmacytogenesis was observed in the T cell zone.
      CONCLUSION: The observed alterations, especially the germinal center architecture
      disturbance (GCAD) with poor centrocyte differentiation, suggest that B cell
      responses during P. berghei ANKA infection in mice are defective, with potential
      impact on B cell memory responses.

PMID- 17506898
TI  - Extracellular ascorbate modulates glutamate dynamics: role of behavioral
      activation.
AB  - BACKGROUND: A physiological increase in extracellular ascorbate (AA), an
      antioxidant vitamin found throughout the striatum, elevates extracellular
      glutamate (GLU). To determine the role of behavioral arousal in this interaction,
      microdialysis was used to measure striatal GLU efflux in rats tested in either a
      lights-off or lights-on condition while reverse dialysis either maintained the
      concentration of AA at 250 microM or increased it to 1000 microM to approximate
      endogenous changes. RESULTS: When lights were off, both locomotion and GLU
      increased regardless of AA dose. In contrast, animals in the lights-on condition
      were behaviorally inactive, and infusion of 1000, but not 250, microM AA
      significantly increased extracellular GLU. Interestingly, when ambient light
      returned to the lights-off group, 1000 microM prolonged the GLU increase relative
      to the 250 microM group. CONCLUSION: Our results not only support evidence that
      elevated striatal AA increases extracellular GLU but also indicate that this
      effect depends on behavioral state and the corresponding level of endogenous GLU
      release.

PMID- 17506899
TI  - Complementary and alternative medicine use among US Navy and Marine Corps
      personnel.
AB  - BACKGROUND: Recently, numerous studies have revealed an increase in complementary
      and alternative medicine (CAM) use in US civilian populations. In contrast, few
      studies have examined CAM use within military populations, which have ready
      access to conventional medicine. Currently, the prevalence and impact of CAM use
      in US military populations remains unknown. METHODS: To investigate CAM use in US
      Navy and Marine Corps personnel, the authors surveyed a stratified random sample
      of 5,000 active duty and Reserve/National Guard members between December 2000 and
      July 2002. Chi-square tests and multivariable logistic regression were used to
      assess univariate associations and adjusted odds of CAM use in this population.
      RESULTS AND DISCUSSION: Of 3,683 service members contacted, 1,446 (39.3%)
      returned a questionnaire and 1,305 gave complete demographic and survey data
      suitable for study. Among respondents, more than 37% reported using at least one
      CAM therapy during the past year. Herbal therapies were among the most commonly
      reported (15.9%). Most respondents (69.8%) reported their health as being very
      good or excellent. Modeling revealed that CAM use was most common among personnel
      who were women, white, and officers. Higher levels of recent physical pain and
      lower levels of satisfaction with conventional medical care were significantly
      associated with increased odds of reporting CAM use. CONCLUSION: These data
      suggest that CAM use is prevalent in the US military and consistent with patterns
      in other US civilian populations. Because there is much to be learned about CAM
      use along with allopathic therapy, US military medical professionals should
      record CAM therapies when collecting medical history data.

PMID- 17506900
TI  - Comparative analysis of differentially expressed genes in normal and white spot
      syndrome virus infected Penaeus monodon.
AB  - BACKGROUND: White spot syndrome (WSS) is a viral disease that affects most of the
      commercially important shrimps and causes serious economic losses to the shrimp
      farming industry worldwide. However, little information is available in terms of
      the molecular mechanisms of the host-virus interaction. In this study, we used an
      expressed sequence tag (EST) approach to observe global gene expression changes
      in white spot syndrome virus (WSSV)-infected postlarvae of Penaeus monodon.
      RESULTS: Sequencing of the complementary DNA clones of two libraries constructed
      from normal and WSSV-infected postlarvae produced a total of 15,981 high-quality
      ESTs. Of these ESTs, 46% were successfully matched against annotated genes in
      National Center of Biotechnology Information (NCBI) non-redundant (nr) database
      and 44% were functionally classified using the Gene Ontology (GO) scheme.
      Comparative EST analyses suggested that, in postlarval shrimp, WSSV infection
      strongly modulates the gene expression patterns in several organs or tissues,
      including the hepatopancreas, muscle, eyestalk and cuticle. Our data suggest that
      several basic cellular metabolic processes are likely to be affected, including
      oxidative phosphorylation, protein synthesis, the glycolytic pathway, and calcium
      ion balance. A group of immune-related chitin-binding protein genes is also
      likely to be strongly up regulated after WSSV infection. A database containing
      all the sequence data and analysis results is accessible at
      http://xbio.lifescience.ntu.edu.tw/pm/. CONCLUSION: This study suggests that WSSV
      infection modulates expression of various kinds of genes. The predicted gene
      expression pattern changes not only reflect the possible responses of shrimp to
      the virus infection but also suggest how WSSV subverts cellular functions for
      virus multiplication. In addition, the ESTs reported in this study provide a rich
      source for identification of novel genes in shrimp.

PMID- 17506901
TI  - X chromosome transmission ratio distortion in Cftr +/- intercross-derived mice.
AB  - BACKGROUND: Cystic fibrosis (CF) mice, created with a genetically engineered
      mutation in the Cystic fibrosis transmembrane conductance regulator (Cftr) gene,
      may develop intestinal plugs which limit their survival past weaning. In a
      studied population of genetically mixed CF mice differences in allelic ratios at
      particular loci, between surviving CF mice and mice with the lethal intestinal
      defect, were used to map cystic fibrosis modifier gene one, Cfm1. Using this
      approach, we previously identified an X chromosome locus which may influence the
      survival to weaning of C57BL/6J x BALB/cJ F2 CF mice. We also detected two
      regions of transmission ratio distortion, independent of Cftr genotype, in a
      limited dataset. To investigate these findings, in this study we have genotyped
      1208 three-week old F2 mice, and 186 day E15.5 embryos, derived from a congenic
      (C57BL/6J x BALB/cJ) F1 Cftr +/- intercross, for the putative distortion regions.
      RESULTS: An excess of homozygous BALB genotypes, compared to Mendelian
      expectations, was detected on chromosomes 5 (p = 5.7 x 10-15) and X (p = 3.0 x 10
      35) in three-week old female mice but transmission ratio distortion was not
      evident in the tested region of chromosome 3 (p = 0.39). Significant pre-weaning
      lethality of CF mice occurred as 11.3% (137/1208) of the three-week old offspring
      were identified as CF mice. X chromosome genotypes were not, however, distorted
      in the female CF mice (p = 0.62), thus the significant non-Mendelian inheritance
      of this locus was dependent on CF status. The survival of CF embryos to day E15.5
      was consistent with Mendelian expectations (42/186 = 23%), demonstrating the loss
      of CF mice to have occurred between E15.5 and three weeks of age. The excess of X
      chromosome homozygous BALB genotypes was recorded in female embryos (p = 0.0048),
      including CF embryos, indicating the distortion to be evident at this age.
      CONCLUSION: Two of three previously suggested loci of transmission ratio
      distortion were replicated as distorted in this mouse cross. The non-Mendelian
      inheritance of X chromosome genotypes implicates this region in the survival to
      weaning of non-CF mice.

PMID- 17506902
TI  - Genome evolution in major Escherichia coli O157:H7 lineages.
AB  - BACKGROUND: Genetic analysis of Escherichia coli O157:H7 strains has shown
      divergence into two distinct lineages, lineages I and II, that appear to have
      distinct ecological characteristics, with lineage I strains more commonly
      associated with human disease. In this study, microarray-based comparative
      genomic hybridization (CGH) was used to identify genomic differences among 31 E.
      coli O157:H7 strains that belong to various phage types (PTs) and different
      lineage-specific polymorphism assay (LSPA) types. RESULTS: A total of 4,084 out
      of 6,057 ORFs were detected in all E. coli O157:H7 strains and 1,751 were
      variably present or absent. Based on this data, E. coli O157:H7 strains were
      divided into three distinct clusters, which consisted of 15 lineage I (LSPA type
      111111), four lineage I/II (designated in this study) (LSPA type 211111) and 12
      lineage II strains (LSPA 222222, 222211, 222212, and 222221), respectively.
      Eleven different genomic regions that were dominant in lineage I strains (present
      in > or =80% of lineage I and absent from > or = 92% of lineage II strains)
      spanned segments containing as few as two and up to 25 ORFs each. These regions
      were identified within E. coli Sakai S-loops # 14, 16, 69, 72, 78, 83, 85, 153
      and 286, Sakai phage 10 (S-loops # 91, 92 and 93) and a genomic backbone region.
      All four lineage I/II strains were of PT 2 and possessed eight of these 11
      lineage I-dominant loci. Several differences in virulence-associated loci were
      noted between lineage I and lineage II strains, including divergence within S
      loop 69, which encodes Shiga toxin 2, and absence of the non-LEE encoded effector
      genes nleF and nleH1-2 and the perC homologue gene pchD in lineage II strains.
      CONCLUSION: CGH data suggest the existence of two dominant lineages as well as
      LSPA type and PT-related subgroups within E. coli O157:H7. The genomic
      composition of these subgroups supports the phylogeny that has been inferred from
      other methods and further suggests that genomic divergence from an ancestral form
      and lateral gene transfer have contributed to their evolution. The genomic
      features identified in this study may contribute to apparent differences in the
      epidemiology and ecology of strains of different E. coli O157:H7 lineages.

PMID- 17506903
TI  - Do supervised weekly exercise programs maintain functional exercise capacity and
      quality of life, twelve months after pulmonary rehabilitation in COPD?
AB  - BACKGROUND: Pulmonary rehabilitation programs have been shown to increase
      functional exercise capacity and quality of life in COPD patients. However,
      following the completion of pulmonary rehabilitation the benefits begin to
      decline unless the program is of longer duration or ongoing maintenance exercise
      is followed. Therefore, the aim of this study is to determine if supervised,
      weekly, hospital-based exercise compared to home exercise will maintain the
      benefits gained from an eight-week pulmonary rehabilitation program in COPD
      subjects to twelve months. METHODS: Following completion of an eight-week
      pulmonary rehabilitation program, COPD subjects will be recruited and randomised
      (using concealed allocation in numbered envelopes) into either the maintenance
      exercise group (supervised, weekly, hospital-based exercise) or the control group
      (unsupervised home exercise) and followed for twelve months. Measurements will be
      taken at baseline (post an eight-week pulmonary rehabilitation program), three,
      six and twelve months. The exercise measurements will include two six-minute walk
      tests, two incremental shuttle walk tests, and two endurance shuttle walk tests.
      Oxygen saturation, heart rate and dyspnoea will be monitored during all these
      tests. Quality of life will be measured using the St George's Respiratory
      Questionnaire and the Hospital Anxiety and Depression Scale. Participants will be
      excluded if they require supplemental oxygen or have neurological or
      musculoskeletal co-morbidities that will prevent them from exercising
      independently. DISCUSSION: Pulmonary rehabilitation plays an important part in
      the management of COPD and the results from this study will help determine if
      supervised, weekly, hospital-based exercise can successfully maintain functional
      exercise capacity and quality of life following an eight-week pulmonary
      rehabilitation program in COPD subjects in Australia.

PMID- 17506904
TI  - Do longer consultations improve the management of psychological problems in
      general practice? A systematic literature review.
AB  - BACKGROUND: Psychological problems present a huge burden of illness in our
      community and GPs are the main providers of care. There is evidence that longer
      consultations in general practice are associated with improved quality of care;
      but this needs to be balanced against the fact that doctor time is a limited
      resource and longer consultations may lead to reduced access to health care. The
      aim of this research was to conduct a systematic literature review to determine
      whether management of psychological problems in general practice is associated
      with an increased consultation length and to explore whether longer consultations
      are associated with better health outcomes for patients with psychological
      problems. METHODS: A search was conducted on Medline (Ovid) databases up to 7
      June 2006. The following search terms, were used:general practice or primary
      health care (free text) or family practice (MeSH)AND consultation length or
      duration (free text) or time factors (MeSH)AND depression or psychological
      problems or depressed (free text).A similar search was done in Web of Science,
      Pubmed, Google Scholar, and Cochrane Library and no other papers were found.
      Studies were included if they contained data comparing consultation length and
      management or detection of psychological problems in a general practice or
      primary health care setting. The studies were read and categories developed to
      enable systematic data extraction and synthesis. RESULTS: 29 papers met the
      inclusion criteria. Consultations with a recorded diagnosis of a psychological
      problem were reported to be longer than those with no recorded psychological
      diagnosis. It is not clear if this is related to the extra time or the
      consultation style. GPs reported that time pressure is a major barrier to
      treating depression. There was some evidence that increased consultation length
      is associated with more accurate diagnosis of psychological problems. CONCLUSION:
      Further research is needed to elucidate the factors in longer consultations that
      are associated with greater detection of psychological problems, and to determine
      the association between the detection of psychological problems and the attitude,
      gender, age or training of the GP and the age, gender and socioeconomic status of
      the patient. These are important considerations if general practice is to deal
      more effectively with people with psychological problems.

PMID- 17506905
TI  - Obesity and pronated foot type may increase the risk of chronic plantar heel
      pain: a matched case-control study.
AB  - BACKGROUND: Chronic plantar heel pain (CPHP) is one of the most common
      musculoskeletal disorders of the foot, yet its aetiology is poorly understood.
      The purpose of this study was to examine the association between CPHP and a
      number of commonly hypothesised causative factors. METHODS: Eighty participants
      with CPHP (33 males, 47 females, mean age 52.3 years, S.D. 11.7) were matched by
      age (+/- 2 years) and sex to 80 control participants (33 males, 47 females, mean
      age 51.9 years, S.D. 11.8). The two groups were then compared on body mass index
      (BMI), foot posture as measured by the Foot Posture Index (FPI), ankle
      dorsiflexion range of motion (ROM) as measured by the Dorsiflexion Lunge Test,
      occupational lower limb stress using the Occupational Rating Scale and calf
      endurance using the Standing Heel Rise Test. RESULTS: Univariate analysis
      demonstrated that the CPHP group had significantly greater BMI (29.8 +/- 5.4
      kg/m2 vs. 27.5 +/- 4.9 kg/m2; P < 0.01), a more pronated foot posture (FPI score
      2.4 +/- 3.3 vs. 1.1 +/- 2.3; P < 0.01) and greater ankle dorsiflexion ROM (45.1
      +/- 7.1 degrees vs. 40.5 +/- 6.6 degrees; P < 0.01) than the control group. No
      difference was identified between the groups for calf endurance or time spent
      sitting, standing, walking on uneven ground, squatting, climbing or lifting.
      Multivariate logistic regression revealed that those with CPHP were more likely
      to be obese (BMI > or = 30 kg/m2) (OR 2.9, 95% CI 1.4 - 6.1, P < 0.01) and to
      have a pronated foot posture (FPI > or = 4) (OR 3.7, 95% CI 1.6 - 8.7, P < 0.01).
      CONCLUSION: Obesity and pronated foot posture are associated with CPHP and may be
      risk factors for the development of the condition. Decreased ankle dorsiflexion,
      calf endurance and occupational lower limb stress may not play a role in CPHP.

PMID- 17506906
TI  - How do we manage the gastrectomy for gastric cancer after coronary artery bypass
      grafting using the right gastroepiploic artery? Report of two cases and a review
      of the literature.
AB  - BACKGROUND: Recently, the right gastroepiploic artery (RGEA) has been used in
      coronary artery bypass grafting (CABG) as an alternative arterial graft.
      Unfortunately, an increased incidence of gastric cancers has been reported after
      CABG using the RGEA. Handling of the RGEA during gastrectomy in these patients
      may cause lethal complications, which sometimes reduces the feasibility of
      curative dissection of lymph nodes at the base of the graft. CASE PRESENTATIONS:
      We describe two cases of gastric cancer undergoing gastrectomy after CABG with
      the use of RGEA. To avoid the potentially fatal coronary event during
      gastrectomy, safe handling of the conduit including preparations for injuries and
      prevention of vessel spasm was performed in both cases, accompanied by an
      adequate monitoring of the systemic circulation. Intraoperative frozen section
      examination showed no lymph node metastasis around the graft in any of the cases;
      therefore, complete lymph node dissection at the base of the graft was not
      undertaken. No complications occurred during the operation. In addition to these
      two cases, twenty-four cases reported in the literatures were reviewed (a total
      of 26 cases). Ten early and 16 advanced gastric cancers were included. Among the
      16 advanced gastric cancer cases, an alternative graft was employed in 8 due to
      the resection of an original graft to complete lymph node dissection. Mere
      handling of a graft often caused lethal complications suggesting that the
      operation should be completed by isolation of the graft. A pedicled graft
      harvesting via the ante-gastric route was popular. However, a skeletonized
      harvesting with resection of the pyloric branches of the RGEA would be better
      because this would interrupt the original lymph flow, which could eliminate the
      need for lymph node dissection and graft isolation. Among the 10 cases having
      early gastric cancers, 6 were found within 1.5 years after CABG. Early detection
      in these 6 cases was possible due to the use of gastric fiberscopic examination
      before and after CABG, which gave them opportunities to receive a less extensive
      operation such as endoscopic mucosal resection. CONCLUSION: Adequate
      intraoperative care as well as an optimal lymph node dissection considering the
      graft harvesting method at the first CABG leads to successful gastrectomy after
      CABG using the RGEA graft. Therefore, this operation should be carried out with
      careful management by both gastrointestinal and cardiovascular surgeons.

PMID- 17506907
TI  - Laser capture microdissection and cDNA array analysis of endometrium identify
      CCL16 and CCL21 as epithelial-derived inflammatory mediators associated with
      endometriosis.
AB  - BACKGROUND: Understanding the pathophysiology of chemokine secretion in
      endometriosis may offer a novel area of therapeutic intervention. This study
      aimed to identify chemokines differentially expressed in epithelial glands in
      eutopic endometrium from normal women and those with endometriosis, and to
      establish the expression profiles of key chemokines in endometriotic lesions.
      METHODS: Laser capture microdissection isolated epithelial glands from
      endometrial eutopic tissue from women with and without endometriosis in the mid
      secretory phase of their menstrual cycles. Gene profiling of the excised glands
      used a human chemokine and receptor cDNA array. Selected chemokines were further
      examined using real-time PCR and immunohistochemistry. RESULTS: 22
      chemokine/receptor genes were upregulated and two downregulated in pooled
      endometrial epithelium of women with endometriosis compared with controls. CCL16
      and CCL21 mRNA was confirmed as elevated in some women with endometriosis
      compared to controls on individual samples. Immunoreactive CCL16 and CCL21 were
      predominantly confined to glands in eutopic and ectopic endometrium: leukocytes
      also stained. Immunoreactive CCL16 was overall higher in glands in ectopic vs.
      eutopic endometrium from the same woman (P < 0.05). Staining for CCL16 and CCL21
      was highly correlated in individual tissues. CONCLUSION: This study provides
      novel candidate molecules and suggests a potential local role for CCL16 and CCL21
      as mediators contributing to the inflammatory events associated with
      endometriosis.

PMID- 17506909
TI  - A cross-national study of the relationship between elderly suicide rates and life
      expectancy and markers of socioeconomic status and health care.
AB  - BACKGROUND: Socioeconomic status may influence cross-national variations in
      elderly suicide rates. METHODS: The relationship between suicide rates in both
      sexes in the age-bands 65-74 years and 75+ years and (i) life expectancy, (ii)
      measures of socioeconomic status (per capita gross national domestic product
      (GDP) and the Gini coeffcient), and (iii) measures of the quality and quantity of
      available healthcare services (the proportion of GDP spent on health, per capita
      expenditure on health and child mortality rates) was examined using data from the
      World Health Organization and the United Nations. RESULTS: The main findings
      were: (i) a significant negative correlation between the Gini coefficient and
      suicide rates for both sexes in both age-bands; (ii) a significant positive
      correlation between per capita expenditure on health and suicide rates for both
      sexes in both age-bands; (iii) the significant positive correlation between the
      proportion of GDP spent on health and suicide rates was only evident in males in
      both age-bands; (iv) a significant negative correlation between child mortality
      rates and suicide rates for both sexes in both age-bands; and, (v) the
      significant positive correlation between life expectancy and suicide rates was
      evident in females in both age-bands. CONCLUSIONS: A potentially testable model
      with five sequential stages was proposed to explain these findings.

PMID- 17506908
TI  - Global gene expression analysis of the mouse colonic mucosa treated with
      azoxymethane and dextran sodium sulfate.
AB  - BACKGROUND: Chronic inflammation is well known to be a risk factor for colon
      cancer. Previously we established a novel mouse model of inflammation-related
      colon carcinogenesis, which is useful to examine the involvement of inflammation
      in colon carcinogenesis. To shed light on the alterations in global gene
      expression in the background of inflammation-related colon cancer and gain
      further insights into the molecular mechanisms underlying inflammation-related
      colon carcinogenesis, we conducted a comprehensive DNA microarray analysis using
      our model. METHODS: Male ICR mice were given a single ip injection of
      azoxymethane (AOM, 10 mg/kg body weight), followed by the addition of 2% (w/v)
      dextran sodium sulfate (DSS) to their drinking water for 7 days, starting 1 week
      after the AOM injection. We performed DNA microarray analysis (Affymetrix
      GeneChip) on non-tumorous mucosa obtained from mice that received AOM/DSS, AOM
      alone, and DSS alone, and untreated mice at wks 5 and 10. RESULTS: Markedly up
      regulated genes in the colonic mucosa given AOM/DSS at wk 5 or 10 included Wnt
      inhibitory factor 1 (Wif1, 48.5-fold increase at wk 5 and 5.7-fold increase at wk
      10) and plasminogen activator, tissue (Plat, 48.5-fold increase at wk 5),
      myelocytomatosis oncogene (Myc, 3.0-fold increase at wk 5), and phospholipase A2,
      group IIA (platelets, synovial fluid) (Plscr2, 8.0-fold increase at wk 10). The
      notable down-regulated genes in the colonic mucosa of mice treated with AOM/DSS
      were the peroxisome proliferator activated receptor binding protein (Pparbp, 0.06
      fold decrease at wk 10) and the transforming growth factor, beta 3 (Tgfb3, 0.14
      fold decrease at wk 10). The inflammation-related gene, peroxisome proliferator
      activated receptor gamma (Ppargamma 0.38-fold decrease at wk 5), was also down
      regulated in the colonic mucosa of mice that received AOM/DSS. CONCLUSION: This
      is the first report describing global gene expression analysis of an AOM/DSS
      induced mouse colon carcinogenesis model, and our findings provide new insights
      into the mechanisms of inflammation-related colon carcinogenesis and the
      establishment of novel therapies and preventative strategies against
      carcinogenesis.

PMID- 17506911
TI  - High rate of conversion to Alzheimer's disease in a cohort of amnestic MCI
      patients.
AB  - BACKGROUND: A large proportion of patients with amnestic mild cognitive
      impairment (MCI) progress to Alzheimer's disease (AD), but the rate of conversion
      is highly variable, depending on selection and inclusion criteria. In the present
      prospective study, amnestic MCI criteria were applied in order to enrich the
      study population with prodromal AD patients. METHODS: A composite CERAD word list
      learning z-score of -1 was applied as a cut-off for memory performance at
      baseline. Competing causes of memory impairment other than prodromal AD were
      actively excluded. A cohort of 88 amnestic MCI patients was included; 75 were
      available for follow-up. RESULTS: After a mean delay of 19 months, 44% were found
      to have converted to AD, corresponding to an annualized conversion rate of 28%.
      The rate of new diagnoses other than stable MCI or AD was 6%. Baseline
      neuropsychological variables were not instrumental to predict progression.
      CONCLUSION: Amnestic MCI patients, as identified by the present set of criteria,
      carry a high risk of median-term progression to AD.

PMID- 17506910
TI  - Physician don't heal thyself: a descriptive study of impaired older doctors.
AB  - BACKGROUND: The growing and welcome interest in the issues leading to distress
      and impairment in younger doctors has not been mirrored by a focus on the similar
      issues in older doctors which is surprising given the aging medical workforce.
      OBJECTIVES: To improve understanding of impairment in older doctors and to
      facilitate the planning of primary prevention strategies. METHOD: Consecutive
      case records of notifications to the Impaired Registrants Program of the New
      South Wales Medical Board, Australia, of doctors over 60 years from January 2000
      to January 2006 (N = 41) were examined. Details of demographics, type of
      practice, nature of referral, medical morbidity, cognitive examination,
      psychiatric diagnosis and outcome of assessment were recorded. RESULTS: Impaired
      older doctors suffered cognitive impairment (54%), substance abuse (29%) and
      depression (22%) and 17% had two comorbid psychiatric conditions. Twelve percent
      had frank dementia. Two work patterns--the "workhorse" and the "dabbler"--were
      observed, as was a culture of postponed retirement due to a sense of obligation
      and working "until you drop." Impaired older doctors were found to have higher
      chronic illness burden compared with community norms. Almost half were the
      subject of patient complaints or of poor performance within ten years of
      presentation. CONCLUSION: To our knowledge there has been no other comprehensive
      examination of patterns of impairment in older doctors. Older doctors are prone
      to suffer "the four Ds": dementia, drugs, drink and depression. We need to
      encourage mature doctors to adapt to age-related changes and illness and validate
      their right to timely and appropriate retirement.

PMID- 17506912
TI  - Prevalence estimates of depression in elderly community-dwelling African
      Americans in Indianapolis and Yoruba in Ibadan, Nigeria.
AB  - BACKGROUND: This is a community-based longitudinal epidemiological comparative
      study of elderly African Americans in Indianapolis and elderly Yoruba in Ibadan,
      Nigeria. METHOD: A two-stage study was designed in which community-based
      individuals were first screened using the Community Screening Interview for
      Dementia. The second stage was a full clinical assessment, which included use of
      the Geriatric Depression Scale, of a smaller sub-sample of individuals selected
      on the basis of their performance in the screening interview. Prevalence of
      depression was estimated using sampling weights according to the sampling
      stratification scheme for clinical assessment. RESULTS: Some 2627 individuals
      were evaluated at the first stage in Indianapolis and 2806 in Ibadan. All were
      aged 69 years and over. Of these, 451 (17.2%) underwent clinical assessment in
      Indianapolis, while 605 (21.6%) were assessed in Ibadan. The prevalence estimates
      of both mild and severe depression were similar for the two sites (p=0.1273 and
      p=0.7093): 12.3% (mild depression) and 2.2% (severe depression) in Indianapolis
      and 19.8% and 1.6% respectively in Ibadan. Some differences were identified in
      association with demographic characteristics; for example, Ibadan men had a
      significantly higher prevalence of mild depression than Indianapolis men
      (p<0.0001). Poor cognitive performance was associated with significantly higher
      rates of depression in Yoruba (p=0.0039). CONCLUSION: Prevalence of depression
      was similar for elderly African Americans and Yoruba despite considerable
      socioeconomic and cultural differences between these populations.

PMID- 17506913
TI  - Nutritional genomics: food industry applications from farm to fork.
AB  - Nutritional genomics is a new and promising science area which can broadly be
      defined as the application of high throughput genomics (transcriptomics,
      proteomics, metabolomics/metabonomics) and functional genomic technologies to the
      study of nutritional sciences and food technology. First utilised in the food
      industry by plant biotechnologists to manipulate plant biosynthetic pathways, the
      use of genomic technologies has now spread within the agriculture sector,
      unleashing a host of new applications (e.g. approaches for producing novel, non
      transgenic plant varietals; identification of genetic markers to guide plant and
      animal breeding programmes; exploration of diet-gene interactions for enhancing
      product quality and plant/animal health). Beyond agriculture, genomic
      technologies are also contributing to the improvement of food processing, food
      safety and quality assurance as well as the development of functional food
      products and the evolution of new health management concepts such as
      'personalised nutrition', an emerging paradigm in which the diet of an individual
      is customised, based on their own genomic information, to optimise health and
      prevent disease. In this review the relevance of nutritional genomics to the food
      industry will be considered and examples given on how this science area is
      starting to be leveraged for economic benefits and to improve human nutrition and
      health.

PMID- 17506914
TI  - Further evidence that food fortification improves micronutrient status.

PMID- 17506915
TI  - Amla (Emblica officinalis Gaertn.) prevents dyslipidaemia and oxidative stress in
      the ageing process.
AB  - Amla (Emblica officinalis Gaertn.) is widely used in Indian medicine for the
      treatment of various diseases. We have investigated the effects of amla on the
      lipid metabolism and protein expression involved in oxidative stress during the
      ageing process. SunAmla or ethyl acetate extract of amla, a polyphenol-rich
      fraction, was administered at a dose of 40 or 10 mg/kg body weight per d for 100
      d to young rats aged 2 months and aged rats aged 10 months. The lipid levels,
      such as cholesterol and TAG, in serum and liver were markedly elevated in aged
      control rats, while they were significantly decreased by the administration of
      amla. The PPARalpha is known to regulate the transcription of genes involved in
      lipid and cholesterol metabolism. The PPARalpha protein level in liver was
      reduced in aged control rats. However, the oral administration of amla
      significantly increased the hepatic PPARalpha protein level. In addition, oral
      administration of amla significantly inhibited the serum and hepatic
      mitochondrial thiobarbituric acid-reactive substance levels in aged rats.
      Moreover, the elevated expression level of bax was significantly decreased after
      the oral administration of amla, while the level of bcl-2 led to a significant
      increase. Furthermore, the expressions of hepatic NF-kappaB, inducible NO
      synthase (iNOS), and cyclo-oxygenase-2 (COX-2) protein levels were also increased
      with ageing. However, amla extract reduced the iNOS and COX-2 expression levels
      by inhibiting NF-kappaB activation in aged rats. These results indicate that amla
      may prevent age-related hyperlipidaemia through attenuating oxidative stress in
      the ageing process.

PMID- 17506916
TI  - Incidence of scabies in Belgium.
AB  - A prospective survey on scabies in Ghent, Belgium was performed in 2004. Sixty
      four individual cases were reported, corresponding to a crude incidence rate of
      28/100,000 inhabitants. The incidence was higher in the elderly (51/100,000 in
      persons aged >75 years) and a higher incidence was also found in immigrants
      (88/100,000). More than 40% of the registered scabies patients had symptoms for
      more than 4 weeks at the time of presentation. In 54% of the consultations, the
      patient had already consulted a physician for his/her skin problem. Of this
      group, 44% had not yet received any scabicidal treatment, indicating that scabies
      was not yet diagnosed or that an inappropriate treatment was prescribed. The
      observations suggest that the diagnosis and/or treatment of scabies in this
      region can still be improved.

PMID- 17506917
TI  - Correlation and agreement between the Mini-mental State Examination and the Clock
      Drawing Test in older adults with low levels of schooling: the Bambui Health
      Aging Study (BHAS).
AB  - BACKGROUND: The aim of the study was to determine the correlation and agreement
      between the Mini-mental State Examination (MMSE) and Clock Drawing Test (CDT),
      administered and scored using Shulman's method (2000), in elderly Brazilian
      adults with very low levels of formal education. METHODS: CDT and MMSE tests,
      performed by a sample of 1118 elderly subjects from a population-based cohort,
      were evaluated. Spearman's correlation coefficient was calculated for the total
      sample and according to gender, age and schooling level. Agreement was assessed
      using receiver operating characteristic (ROC) analysis. RESULTS: CDTs with high
      scores had high corresponding MMSE scores whereas CDTs with low scores had a wide
      range of corresponding MMSE scores. Correlation was moderate (rho=0.64) and no
      difference was found according to gender, age or schooling level. For CDT cut-off
      3/4, the best MMSE cut-off was 27/28 and agreement between tests was 75.1%.
      CONCLUSIONS: Correlation between tests was moderate. Subjects who performed well
      on the CDT could be expected to obtain high MMSE scores. Although one test does
      not substitute for the other, the CDT may be more practical in developing
      countries where resources are limited and low education is common in the elderly,
      as well as in situations where time for assessment or screening is limited.
      Moreover, the CDT may be sensitive to cognitive domains not assessed by the MMSE.

PMID- 17506918
TI  - Differences in the social networks of ethnic Vietnamese and non-Vietnamese
      injecting drug users and their implications for blood-borne virus transmission.
AB  - The social networks of 49 ethnic Vietnamese injecting drug users (IDUs) and 150
      IDUs of other ethnicities recruited in Melbourne, Australia, were examined for
      ethnic differences in distribution of hepatitis C virus infection risk using
      social network analysis and molecular epidemiology. Vietnamese IDUs were more
      highly connected than non-Vietnamese IDUs, and more likely to be members of dense
      injecting sub-networks. More related infections were detected in IDUs with
      discordant ethnicities than were captured in the social network data;
      nonetheless, most dyads and most IDU pairs with related infections had matching
      ethnicity, confirming that mixing was assortative on that criterion. Mixing was
      not obviously dissortative by risk; low-risk Vietnamese IDUs injected more
      frequently than did correspondingly low-risk non-Vietnamese IDUs, but results for
      other measures were reversed or equivocal. Network measurements suggest that
      ethnic Vietnamese IDUs are at elevated risk of blood-borne infection, a
      conclusion supported by their relatively high HIV prevalence.

PMID- 17506919
TI  - Invasive pneumococcal disease in New Zealand 1998-2005: capsular serotypes and
      antimicrobial resistance.
AB  - Isolates from 3903 cases of invasive pneumococcal disease (IPD) were referred to
      the national reference laboratory over the 8 years, 1998-2005, as part of the
      laboratory-based surveillance of this disease in New Zealand. All isolates were
      serotyped and their antimicrobial susceptibility was tested. The incidence of IPD
      was highest in young children, with an average annual incidence of 100.8/100,000
      in infants aged <2 years. There were changes in the prevalence of several of the
      serotypes during the 8-year period. Overall the seven serotypes included in the 7
      valent pneumococcal conjugate vaccine, 4, 6B, 9V, 14, 18C, 19F and 23F, were the
      most common serotypes and accounted for 80.9% of the disease in infants aged <2
      years. There was no overall change in penicillin resistance or non-susceptibility
      during the 8 years, and rates were 7.1% and 17.1%, respectively, in 2005. In
      contrast, cefotaxime and erythromycin resistance increased to reach 3.1% and
      12.2%, respectively, by 2005.

PMID- 17506920
TI  - Estimating the impact of vaccination using age-time-dependent incidence rates of
      hepatitis B.
AB  - The objective of this study was to model the age-time-dependent incidence of
      hepatitis B while estimating the impact of vaccination. While stochastic
      models/time-series have been used before to model hepatitis B cases in the
      absence of knowledge on the number of susceptibles, this paper proposed using a
      method that fits into the generalized additive model framework. Generalized
      additive models with penalized regression splines are used to exploit the
      underlying continuity of both age and time in a flexible non-parametric way.
      Based on a unique case notification dataset, we have shown that the implemented
      immunization programme in Bulgaria resulted in a significant decrease in
      incidence for infants in their first year of life with 82% (79-84%). Moreover, we
      have shown that conditional on an assumed baseline susceptibility percentage, a
      smooth force-of-infection profile can be obtained from which two local maxima
      were observed at ages 9 and 24 years.

PMID- 17506921
TI  - Investigation into the seasonal salmonellosis in lactating dairy cattle.
AB  - Sporadic salmonellosis has been reported in mature lactating dairy cattle in the
      southwestern United States and is an intriguing problem in that Salmonella can be
      cultured from faecal samples of these cattle throughout the year. However, it is
      pathogenic only during late summer/early autumn and in certain years. We sampled
      apparently healthy (n=10) and diarrhoeic (n=10) cattle during an outbreak on a
      2000 head dairy in 2003. The following year, monthly faecal (from the same 30
      head), total mixed ration, water, and pen soil samples were collected for
      Salmonella culture. No serogroup, serotype, genetic, or antimicrobial
      susceptibility differences were observed in comparison of isolates from healthy
      and sick cattle. During year 2 of the study, Salmonella was routinely cultured
      (although highly variable from month to month) from the cattle and the
      environment, although no outbreak of salmonellosis was observed.

PMID- 17506922
TI  - A systematic review of existing data on long-term lithium therapy:
      neuroprotective or neurotoxic?
AB  - Lithium is an efficacious agent for the treatment of bipolar disorder, but it is
      unclear to what extent its long-term use may result in neuroprotective or toxic
      consequences. Medline was searched with the combination of the word 'Lithium'
      plus key words that referred to every possible effect on the central nervous
      system. The papers were further classified into those supporting a
      neuroprotective effect, those in favour of a neurotoxic effect and those that
      were neutral. The papers were classified into research in humans, animal and in
      vitro research, case reports, and review/opinion articles. Finally, the Natural
      Standard evidence-based validated grading rationale was used to validate the
      data. The Medline search returned 970 papers up to February 2006. Inspection of
      the abstracts supplied 214 papers for further reviewing. Eighty-nine papers
      supported the neuroprotective effect (6 human research, 58 animal/in vitro, 0
      case reports, 25 review/opinion articles). A total of 116 papers supported the
      neurotoxic effect (17 human research, 23 animal/in vitro, 60 case reports, 16
      review/opinion articles). Nine papers supported no hypothesis (5 human research,
      3 animal/in vitro, 0 case reports, 1 review/opinion articles). Overall, the
      grading suggests that the data concerning the effect of lithium therapy is that
      of level C, that is 'unclear or conflicting scientific evidence' since there is
      conflicting evidence from uncontrolled non-randomized studies accompanied by
      conflicting evidence from animal and basic science studies. Although more papers
      are in favour of the toxic effect, the great difference in the type of papers
      that support either hypothesis, along with publication bias and methodological
      issues make conclusions difficult. Lithium remains the 'gold standard' for the
      prophylaxis of bipolar illness, however, our review suggests that there is a rare
      possibility of a neurotoxic effect in real-life clinical practice even in closely
      monitored patients with 'therapeutic' lithium plasma levels. It is desirable to
      keep lithium blood levels as low as feasible with prophylaxis.

PMID- 17506923
TI  - Neuropsychological and behavioural disinhibition in adult ADHD compared to
      borderline personality disorder.
AB  - BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) is thought
      to be an inhibitory disorder, the question remains of how specific the inhibitory
      deficit is in adults and whether it distinguishes ADHD from borderline
      personality disorder (BPD), with which it shares several clinical features,
      particularly impulsiveness. METHOD: The study assessed various motor and
      cognitive inhibitory functions (inhibition of prepotent, ongoing and interfering
      responses) in addition to working memory in adult ADHD patients with and without
      BPD, compared to subjects with BPD alone and controls. In addition, questionnaire
      data on various aspects of impulsiveness and anger regulation were assessed in
      all groups. RESULTS: ADHD patients performed worse than BPD individuals and
      controls in two inhibitory tasks: the stop signal task and the conflict module of
      the Attentional Network Task (ANT). In addition, they exhibited longer reaction
      times (RTs) and higher intra-individual variance in nearly all attentional tasks.
      The co-morbid group exhibited poor performance on the stop signal task but not on
      the conflict task. The BPD group barely differed from controls in
      neuropsychological performance but overlapped with ADHD in some behavioural
      problems, although they were less severe on the whole. CONCLUSIONS: Impaired
      inhibition is a core feature in adults with ADHD. In addition, slow RTs and high
      intra-individual variance in performance may reflect deficits in the regulation
      of activation and effort in ADHD patients. ADHD and BPD share some symptoms of
      behavioural dysregulation without common cognitive deficits, at least in the
      attentional realm.

PMID- 17506924
TI  - Confabulation in schizophrenia and its relationship to clinical and
      neuropsychological features of the disorder.
AB  - BACKGROUND: A form of confabulation has been documented in schizophrenia and
      appears to be related to the symptom of thought disorder. It is unclear whether
      it is associated with the same pattern of neuropsychological deficits as
      confabulation in neurological patients. METHOD: Thirty-four patients with chronic
      schizophrenia, including those with and without thought disorder, and 17 healthy
      controls were given a fable recall task to elicit confabulation. They were also
      examined on a range of executive, episodic and semantic memory tests. RESULTS:
      Confabulation was seen at a significantly higher rate in the schizophrenic
      patients than the controls, and predominated in those with thought disorder.
      Neuropsychologically, it was not a function of general intellectual impairment,
      and was not clearly related to episodic memory or executive impairment. However,
      there were indications of an association with semantic memory impairment.
      CONCLUSIONS: The findings support the existence of a form of confabulation in
      schizophrenia that is related to thought disorder and has a different
      neuropsychological signature to the neurological form of the symptom.

PMID- 17506925
TI  - Advances in genetic findings on attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common, childhood-onset
      neurodevelopmental disorder with adverse consequences during adult life. Family,
      twin and adoption studies show that genetic factors contribute to the aetiology
      of ADHD and that environmental factors also play a role. Family and twin studies
      have shown the importance of genetic influences on continuity in ADHD over time
      and in accounting for the co-occurrence of ADHD and conduct disorder problems. In
      meta-analyses of molecular genetic studies, the 48-bp variable number tandem
      repeat (VNTR) variant in the dopamine D4 gene and the CA(n) microsatellite marker
      in the D5 receptor gene have been found to be repeatedly associated with ADHD.
      Results from meta-analyses of the 480-bp VNTR in the dopamine transporter gene
      are mixed. Several genetic studies have also identified genetic variants that are
      related to specific clinical and developmental features of ADHD. In the next few
      years, a new generation of much larger-scale genetic studies should lead to the
      identification of further ADHD susceptibility genes. Such studies will also need
      to be integrated with other areas of neuroscience, clinical and epidemiological
      research to investigate how specific gene variants exert risk effects, interact
      with environmental factors and enable identification of the underlying causal
      mechanisms that lead to ADHD.

PMID- 17506926
TI  - Growth pattern and risk of schizophrenia.
AB  - BACKGROUND: Foetal nutrition and growth seem to affect the risk of developing
      schizophrenia. Exposure to famine during foetal development and low birthweight
      increase the risk. However, few studies have investigated the association between
      schizophrenia and adult height and weight or patterns of growth. METHOD: The
      study population consisted of two subpopulations: families with at least one
      member with schizophrenia, and families of offspring of mothers with psychotic
      disorder, and controls. Using a seven-parameter model of height growth curves, we
      compared the parameters of persons who later developed schizophrenia and their
      unaffected siblings from the same families. We also studied how growth curve
      parameters differed in children with genetic risk for schizophrenia and controls,
      and whether weight, height and body mass index (BMI) at different ages predicted
      later development of schizophrenia. RESULTS: The predicted growth curves based on
      a parametric model were nearly identical for persons with schizophrenia and their
      unaffected siblings. Adult height of daughters of mothers with psychoses was
      borderline significantly (p=0.0536) lower compared to controls, while no
      difference was detected among sons (p=0.3283). CONCLUSIONS: No association
      between growth characteristics and schizophrenia in families with at least one
      member with schizophrenia was found. Family-related factors should be taken into
      account as possible confounders in future studies on growth and schizophrenia.

PMID- 17506927
TI  - The association between C-reactive protein concentration and depression in later
      life is due to poor physical health: results from the Health in Men Study (HIMS).
AB  - BACKGROUND: C-reactive protein (CRP) is a non-specific marker of inflammation
      that has been associated with depression and vascular disease, particularly in
      men. This study aimed to investigate the association between high CRP
      concentration and depression while taking physical health into account. METHOD: A
      cross-sectional study of a community-dwelling sample of 5438 men aged 70+.
      Participants with scores > or =7 on the 15-item Geriatric Depression Scale (GDS
      15) were considered to display clinically significant depressive symptoms. We
      measured the serum concentration of CRP with a high-sensitivity assay. The
      assessment of physical co-morbidity included three components: the Charlson
      weighted index, self-report of major health events on a standardized
      questionnaire, and the physical component of the 36-item Short-Form Health Survey
      (SF-36). Other measured factors included age, native language, education, a
      standardized socio-economic index, smoking, prior or current history of
      depression treatment, cognitive impairment (Mini-Mental State Examination score <
      24 and body mass index (BMI). RESULTS: Participants with depression(n=340)
      wereolder than their controls without depression (age in years: 76.6 +/- 4.4 v.
      75.4+/- 4.1). Men with CRP concentration > 3 mg/l had an increased odds ratio
      (OR) [1.59, 95% confidence interval (CI) 1.20-2.11] of being depressed compared
      to men with CRP 3 mg/l. This association became non-significant once we adjusted
      the analysis for the measures of physical co-morbidity and other confounding
      factors (OR 1.22, 95% CI 0.86-1.73). CONCLUSIONS: The physiological mechanisms
      that lead to the onset and maintenance of depressive symptoms in older men remain
      to be determined, but CRP concentration is unlikely to play a significant role in
      that process.

PMID- 17506928
TI  - Molecular phylogeny of clade III nematodes reveals multiple origins of tissue
      parasitism.
AB  - Molecular phylogenetic analyses of 113 taxa representing Ascaridida,
      Rhigonematida, Spirurida and Oxyurida were used to infer a more comprehensive
      phylogenetic hypothesis for representatives of 'clade III'. The posterior
      probability of multiple alignment sites was used to exclude or weight characters,
      yielding datasets that were analysed using maximum parsimony, likelihood, and
      Bayesian inference methods. Phylogenetic results were robust to differences among
      inference methods for most high-level taxonomic groups, but some clades were
      sensitive to treatments of characters reflecting differences in alignment
      ambiguity. Taxa representing Camallanoidea, Oxyurida, Physalopteroidea,
      Raphidascarididae, and Skrjabillanidae were monophyletic in all 9 analyses
      whereas Ascaridida, Ascarididae, Anisakidae, Cosmocercoidea, Habronematoidea,
      Heterocheilidae, Philometridae, Rhigonematida and Thelazioidea were never
      monophyletic. Some clades recovered in all trees such as Dracunculoidea and
      Spirurina included the vast majority of their sampled species, but were non
      monophyletic due to the consistent behaviour of one or few 'rogue' taxa.
      Similarly, 102 of 103 clade III taxa were strongly supported as monophyletic, yet
      clade III was paraphyletic due to the grouping of Truttaedacnitis truttae with
      the outgroups. Mapping of host 'habitat' revealed that tissue-dwelling
      localization of nematode adults has evolved independently at least 3 times, and
      relationships among Spirurina and Camallanina often reflected tissue predilection
      rather than taxonomy.

PMID- 17506929
TI  - A heterologous prime-boost vaccination regime using DNA and a vaccinia virus,
      both expressing GRA4, induced protective immunity against Toxoplasma gondii
      infection in mice.
AB  - SUMMARYThe dense granule antigen 4 (GRA4) is known as an immundominant antigen of
      Toxoplasma gondii and, therefore, is considered as a vaccine candidate. For
      further evaluation of its vaccine effect, a recombinant plasmid and vaccinia
      virus, both expressing GRA4, were constructed, and a heterologous prime-boost
      vaccination regime was performed in a mouse model. The mice immunized with the
      heterologous prime-boost vaccination regime showed a high level of specific
      antibody response against GRA4 and a significantly high level of gamma interferon
      (IFN-gamma) production and survived completely against a subsequent challenge
      infection with a lethal dose of T. gondii. In addition, the formation of cysts
      was inhibited in the mice vaccinated with the heterologous prime-boost
      vaccination regime. These results demonstrate that the heterologous prime-boost
      vaccination regime using DNA and a vaccinia virus, both expressing GRA4, could
      induce both humoral and cellular immune responses and provide effective
      protection against lethal acute and chronic T. gondii infections in mice.

PMID- 17506930
TI  - Adaptation of Cryptosporidium oocysts to different excystation conditions.
AB  - Within the genus Cryptosporidium 2 lineages have evolved, one adapted to the acid
      environment of the stomach and abomasum, the other comprising parasites that
      multiply in the small intestine. We tested whether the release of sporozoites
      from oocysts, a process known as excystation, is triggered by conditions which
      mimic the site of infection. Specifically, we exposed oocysts from gastric and
      intestinal Cryptosporidium species to acid conditions or to a neutral solution of
      taurocholic acid, at 37 degrees C. We found that oocysts from the gastric species
      C. muris and C. andersoni excysted in both conditions, whereas the intestinal
      species C. parvum and C. hominis did not respond to acid. When the effect of
      temperature alone was tested on C. muris and C. parvum, only oocysts from the
      former species excysted in significant numbers. Oocysts from intestinal species
      did not respond to temperature alone, nor to acidity. These observations are
      consistent with the need of gastric species to rapidly excyst and release the
      sporozoites upon ingestion, and indicate that Cryptosporidium oocysts have
      evolved to maximize delivery of sporozoites to the region of the gastro
      intestinal tract where the parasite multiplies.

PMID- 17506931
TI  - Dietary soya intake alters plasma antioxidant status and lipid peroxidation in
      postmenopausal women with the metabolic syndrome.
AB  - Postmenopausal women with the metabolic syndrome are at high risk of oxidative
      stress. Several studies have suggested possible antioxidant properties of soya,
      but little evidence is available regarding the effect of soya on oxidative stress
      in postmenopausal women with the metabolic syndrome. The objective of the present
      study was to determine the effects of soya consumption on plasma total
      antioxidant capacity (TAC) and malondialdehyde (MDA) level in postmenopausal
      women with the metabolic syndrome. A randomised cross-over trial was undertaken
      on forty-two postmenopausal women with the metabolic syndrome. Participants were
      randomly assigned to consume a control (Dietary Approaches to Stop Hypertension;
      DASH) diet, a soya protein diet, or a soya nut diet, each for 8 weeks. Red meat
      in the DASH diet (one serving per d) was replaced by soya protein in the soya
      protein period and by soya nuts in the soya nut period. Significant differences
      between the end values of the control diet, soya protein diet and soya nut diet
      were seen for MDA (0.70, 0.64 and 0.63 mumol/l; global P < 0.01). The results
      also showed a significant difference between the end values for TAC (1950, 2030
      and 2110 mumol/l, respectively; P < 0.01). The difference from control for TAC
      was +4.5 % (P < 0.01) in the soya nut period and +5.8 % (P < 0.01) in the soya
      protein regimen. Both soya nuts and soya protein decreased MDA significantly
      compared with the control diet (difference from control was - 7.9 % (P < 0.01) in
      the soya nut period and - 9.4 % (P < 0.01) in the soya protein diet). We conclude
      that soya consumption reduces plasma MDA and increases plasma TAC levels in
      postmenopausal women with the metabolic syndrome.

PMID- 17506932
TI  - Neurophysiological basis of penile erection.
AB  - Penile erection involves a complex interaction between the central nervous system
      and local factors. It is a neurovascular event modulated by psychological and
      hormonal factors. The discovery of nitric oxide (NO) as an intercellular
      messenger or neurotransmitter paved the way for identifying important mechanisms
      underlying physiological and pathophysiological events in the penis, in addition
      to providing the knowledge for the development of new therapeutics based on a
      novel concept of molecule and cell interaction. Despite the fact that sinusoidal
      endothelial cells also produce and release NO in response to chemical and
      possibly physical stimuli, roles of neurogenic NO in penile erection appear to be
      more attractive and convincing, since the pharmacological neuromodulation
      represents an essential step to attaining penile erection. Erectile dysfunction
      (ED) is caused by a variety of pathogenic factors, particularly impaired
      formation and action of NO. Hence, a thorough knowledge of the physiology of
      erection is essential for future pharmacological innovations in the field of male
      ED, particularly targeting NO or intracellular cyclic GMP, which represent the
      most promising therapeutic approach to treat patients with ED.

PMID- 17506933
TI  - Requirement of PSD-95 for dopamine D1 receptor modulating glutamate NR1a/NR2B
      receptor function.
AB  - AIM: To elucidate the role of scaffold protein postsynaptic density (PSD)-95 in
      the dopamine D1 receptor (D1R)-modulated NR1a/NR2B receptor response. METHODS:
      The human embryonic kidney 293 cells expressing D1R (tagged with the enhanced
      yellow fluorescent protein) and NR1a/NR2B with or without co-expression of PSD-95
      were used in the experiments. The Ca2+ influx measured by imaging technique was
      employed to monitor N-methyl-D-aspartic acid receptors (NMDAR) function. RESULTS:
      The application of dopamine (DA, 100 micromol/L) did not alter glutamate/glycine
      (Glu/Gly)-induced NMDAR-mediated Ca2+ influx in cells only expressing the
      D1R/NR1a/NR2B receptor. However, DA increased Glu/Gly-induced Ca2+ influx in a
      concentration-dependent manner while the cells were co-expressed with PSD-95. D1R
      stimulated Ca2+ influx was inhibited by a selective D1R antagonist SCH23390.
      Moreover, pre-incubation with either the protein kinase A (PKA) inhibitor H89, or
      the protein kinase C (PKC) inhibitor chelerythrine attenuated D1R-enhanced Ca2+
      influx induced by the N-methyl-D-aspartic acid (NMDA) agonist. The results
      clearly indicate that D1R-modulated NR1a/NR2B receptor function depends on PSD-95
      and is subjected to the regulation of PKA and PKC. CONCLUSION: The present study
      provides the first evidence that PSD-95 is essential in D1R-regulated NR1a/NR2B
      receptor function.

PMID- 17506934
TI  - Minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal
      cerebral ischemia in rats.
AB  - AIM: To determine whether the anti-inflammatory effect of minocycline on
      postischemic brain injury is mediated by the inhibition of 5-lipoxygenase (5-LOX)
      expression and enzymatic activation in rats. METHODS: Focal cerebral ischemia was
      induced for 30 min with middle cerebral artery occlusion, followed by
      reperfusion. The ischemic injuries, endogenous IgG exudation, the accumulation of
      neutrophils and macrophage/microglia, and 5-LOX mRNA expression were determined
      72 h after reperfusion. 5-LOX metabolites (leukotriene B4 and cysteinyl
      leukotrienes) were measured 3 h after reperfusion. RESULTS: Minocycline (22.5 and
      45 mg/kg, ip, for 3 d) attenuated ischemic injuries, IgG exudation, and the
      accumulation of neutrophils and macrophage/microglia 72 h after reperfusion. It
      also inhibited 5-LOX expression 72 h after reperfusion and the production of
      leukotrienes 3 h after reperfusion. CONCLUSION: Minocycline inhibited
      postischemic brain inflammation, which might be partly mediated by the inhibition
      of 5-LOX expression and enzymatic activation.

PMID- 17506935
TI  - Abrupt changes in FKBP12.6 and SERCA2a expression contribute to sudden occurrence
      of ventricular fibrillation on reperfusion and are prevented by CPU86017.
AB  - AIM: The occurrence of ventricular fibrillation (VF) is dependent on the
      deterioration of channelopathy in the myocardium. It is interesting to
      investigate molecular changes in relation to abrupt appearance of VF on
      reperfusion. We aimed to study whether changes in the expression of FKBP12.6 and
      SERCA2a and the endothelin (ET) system on reperfusion against ischemia were
      related to the rapid occurrence of VF and whether CPU86017, a class III
      antiarrhythmic agent which blocks I(Kr), I(Ks), and I(Ca.L), suppressed VF by
      correcting the molecular changes on reperfusion. METHODS: Cardiomyopathy (CM) was
      produced by 0.4 mg/kg sc L-thyroxin for 10 d in rats, and subjected to 10 min
      coronary artery ligation/reperfusion on d 11. Expressions of the Ca2+ handling
      and ET system and calcium transients were conducted and CPU86017 was injected (4
      mg/kg, sc) on d 6-10. RESULTS: A high incidence of VF was found on reperfusion of
      the rat CM hearts, but there was no VF before reperfusion. The elevation of
      diastolic calcium was significant in the CM myocytes and exhibited abnormality of
      the Ca2+ handling system. The rapid downregulation of mRNA and the protein
      expression of FKBP12.6 and SERCA2a were found on reperfusion in association with
      the upregulation of the expression of the endothelin-converting enzyme (ECE) and
      protein kinase A (PKA), in contrast, no change in the ryanodine type 2 receptor
      (RyR2), phospholamban (PLB), endothelin A receptor (ETAR), and iNOS was found.
      CPU86017 removed these changes and suppressed VF. CONCLUSION: Abrupt changes in
      the expression of FKBP12.6, SERCA2a, PKA, and ECE on reperfusion against
      ischemia, which are responsible for the rapid occurrence of VF, have been
      observed. These changes are effectively prevented by CPU86017.

PMID- 17506936
TI  - Biphasic effects of haloperidol on sodium currents in guinea pig ventricular
      myocytes.
AB  - AIM: To study the effects of haloperidol on sodium currents (I(Na)) in guinea pig
      ventricular myocytes. METHOD: Whole-cell patch clamp technique was employed to
      evaluate the effects of haloperidol on I(Na) in individual ventricular myocytes.
      RESULTS: Haloperidol (0.1-3 micromol/L) inhibited I(Na) in a concentration
      dependent manner with an IC50 of 0.253+/-0.015 micromol/L. The inhibition rate of
      haloperidol (0.3 micromol/L) on I(Na) was 22.14%+/-0.02%, and the maximum
      conductance was reduced. Haloperidol significantly reduced the midpoints for the
      activation and inactivation of I(Na) by 2.09 and 4.09 mV, respectively. The time
      constant of recovery was increased. The increase in time intervals could only
      recover by 90.14%+/-1.4% (n=6); however, haloperidol at 0.03 micromol/L enhanced
      I(Na) conductance. The midpoints for the activation and inactivation of I(Na)
      were shifted by 1.38 and 5.69 mV, respectively, at this concentration of
      haloperidol. CONCLUSION: Haloperidol displayed a biphasic effect on I(Na) in
      guinea pig cardiac myocytes. High concentrations of haloperidol inhibited I(Na),
      while lower concentrations of haloperidol shifted the activation and inactivation
      curve to the left. Full recovery of recovery curve was not achieved after 0.3
      micromol/L haloperidol administration, indicating that the drug affects the
      inactivated state of sodium channels.

PMID- 17506937
TI  - Depside salts from Salvia miltiorrhiza improve myocardial microperfusion in rats
      using laser Doppler flowmetry.
AB  - AIM: To investigate the effects of depside salts from Salvia miltiorrhiza on
      myocardial microperfusion and systemic hemodynamics in open-chest anaesthetized
      Sprague-Dawley rats. METHODS: Myocardial microperfusion was measured by laser
      Doppler flowmetry with a needle probe; cardiac output (CO) was determined using
      ultrasonic Doppler flowmetry. Other hemodynamic parameters, including femoral
      artery blood pressure, cardiac inotropy, and systemic vascular resistance (SVR)
      were simultaneously recorded by the PowerLab system. RESULTS: Intravenous
      administration of S miltiorrhiza depside salts resulted in a significant
      immediate increase in CO and cardiac inotropy, but a fall in SVR. S miltiorrhiza
      depside salts (30 mg/kg and 60 mg/kg) promoted cardiac index (CI) by 12.2%+/-6.3%
      (P<0.01 vs baseline) and 20.1%+/-3.5% (P<0.01), respectively. Myocardial
      microperfusion maximally increased by 6.3%+/-2.9% (P<0.01) and 9.6%+/-4.0%
      (P<0.01) for 30 mg/kg and 60 mg/kg S miltiorrhiza depside salts, respectively.
      CONCLUSION: These results indicated that S miltiorrhiza depside salts improved
      myocardial micro-perfusion, as well as CO.

PMID- 17506938
TI  - Real-time detection of alpha1A-AR movement stimulated by phenylephrine in single
      living cells.
AB  - AIM: To investigate the movement of alpha(1A)-adrenergic receptors(alpha(1A)-AR)
      stimulated by agonist, phenylephrine (PE), and the dynamics of receptor movement
      in real time in single living cells with millisecond resolution. METHODS: We
      labeled alpha(1A)-AR using the monoclonal, anti-FLAG (a kind of tag) antibody and
      Cy3-conjugated goat anti-mouse IgG and recorded the trajectory of their transport
      process in living HEK293A cells stimulated by agonist, PE, and then analyzed
      their dynamic properties. RESULTS: The specific detection of alpha(1A)-AR on the
      surface of living HEK293A-alpha(1A) cells was achieved. alpha(1A)-AR internalize
      under the stimulation of PE. After the cells were stimulated with PE for 20 min,
      apparent colocalization was found between alpha(1A)-AR and F-actins. After 40 min
      stimulation of PE, trajectories of approximate linear motion in HEK293A-alpha(1A)
      cells were recorded, and their velocity was calculated. CONCLUSION: The specific
      labeling method on the living cell surface provides a convenient means of real
      time detection of the behavior of surface receptors. By this method we were able
      to specifically detect alpha(1A)-AR and record the behavior of individual
      particles of receptors with 50 ms exposure time in real time in single living
      cells.

PMID- 17506939
TI  - Activation of extracellular signal-regulated kinase during silibinin-protected,
      isoproterenol-induced apoptosis in rat cardiac myocytes is tyrosine kinase
      pathway-mediated and protein kinase C-dependent.
AB  - AIM: To investigate the mechanism of silibinin-protected isoproterenol-induced
      apoptosis in rat cardiac myocytes. METHODS: The viability of rat cardiac myocytes
      was measured by MTT method. The apoptotic ratio was measured by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Protein kinase C
      (PKC) activity assay was carried out according to the instructions of the PepTag
      non-radioactive protein kinase C assay kit. Western blot analysis was used to
      evaluate the level of Ras, Raf-1 and mitogen-activated protein kinase (MAPK)
      expression. RESULTS: The protective effects of silibinin were significantly
      suppressed by inhibitors, including genistein, manumycin A and GW5074 [inhibitors
      for protein tyrosine kinases (PTK), Ras and Raf-1, respectively]. The exposure of
      rat cardiac myocytes to isoproterenol alone caused decreased PKC activity, which
      was prevented by pretreatment with silibinin dose-dependently. Simultaneously,
      the increased expression of Ras and Raf-1 activated by silibinin were blocked by
      the PKC inhibitor, stauroporine. In addition, the extracellularly responsive
      kinase (ERK) inhibitor, PD98059, suppressed silibinin-protected apoptosis,
      whereas the p38 MAPK inhibitor, SB203580, protected cardiac myocytes from
      isoproterenol-induced injury, and the c-Jun N-terminal kinase (JNK) inhibitor,
      SP600125 had no protective effects. Furthermore, Western blot analysis showed
      that the expression of phosphorylated ERK was increased by silibinin, the
      expression of phosphorylated p38 MAPK was decreased and total ERK, p38, JNK and
      phosphorylated JNK MAPK did not change after treatment with both isoproterenol
      and silibinin. Furthermore, pretreatment of cardiac myocyte with PKC, Ras and Raf
      inhibitors significantly blocked ERK phosphorylation. CONCLUSION: Silibinin is
      suggested to protect isoproterenol-induced rat cardiac myocyte apoptosis by
      activating the tyrosine kinase pathway, PKC and MAPK pathways.

PMID- 17506940
TI  - High-throughput real-time assay based on molecular beacons for HIV-1 integrase 3'
      processing reaction.
AB  - AIM: To develop a high-throughput real-time assay based on molecular beacons to
      monitor the integrase 3'-processing reaction in vitro and apply it to inhibitor
      screening. METHODS: The recombinant human immunodeficiency virus (HIV)-1
      integrase (IN) is incubated with a 38 mer oligonucleotide substrate, a sequence
      identical to the U5 end of HIV-1 long terminal repeats (LTR). Based on the
      fluorescence properties of molecular beacons, the substrate is designed to form a
      stem-loop structure labeled with a fluorophore at the 5' end and a quencher at
      the 3' end. IN cleaves the terminal 3'-dinucleotide containing the quencher,
      resulting in an increase in fluorescence which can be monitored on a
      spectrofluorometer. To optimize this assay, tests were performed to investigate
      the effects of substrates, enzyme and the metal ion concentrations on the IN
      activity and optimal parameters were obtained. Moreover, 2 IN inhibitors were
      employed to test the performance of this assay in antiviral compound screening.
      RESULTS: The fluorescent intensity of the reaction mixture varies linearly with
      time and is proportional to the velocity of the 3'-processing reaction. Tests
      were performed and the results showed that the optimal rate was obtained for a
      reaction mixture containing 50 mg/L recombinant HIV-1 IN, 400 nmol/L substrate,
      and 10 mmol/L Mn(2+). The IN 3'-processing reaction under the optimal conditions
      showed a more than 18-fold increase in the fluorescence intensity compared to the
      enzyme-free control. The IC50 values of the IN inhibitors obtained in our assay
      were similar to the values obtained from a radiolabeled substrate assay.
      CONCLUSION: Our results demonstrated that this is a fast, reliable, and sensitive
      method to monitor HIV IN 3'-processing reaction and that it can be used for
      inhibitor screening.

PMID- 17506941
TI  - Effects of Ginkgo biloba on prevention of development of experimental diabetic
      nephropathy in rats.
AB  - AIM: To observe the preventive and therapeutic effects of Ginkgo biloba extract
      (GbE) on early experimental diabetic nephropathy (DN) in rats. METHODS: After an
      early DN model was induced by streptozotocin, rats were administered GbE at 3
      doses for 12 weeks. Fasting blood glucose, creatinine (Cr), blood urea nitrogen
      (BUN), urine protein, kidney index, anti-oxidase, advanced glycosylation end
      products (AGE), collagen IV and laminin, matrix metalloproteinases-2 (MMP-2) and
      the tissue inhibitor of metalloproteinase-2 (TIMP-2), connective tissue growth
      factor (CTGF), and transforming growth factor-beta1 (TGF-beta1) mRNA were
      measured by different methods. The ultrastructural morphology and the thickness
      of glomerular base membrane (GBM) were observed by a transmission electron
      microscope. RESULTS: For the GbE-treated DN rats, when compared with the vehicle
      treated DN rats, the fasting blood glucose level, Cr, BUN, urine protein level,
      and the intensity of oxidative stress were significantly decreased. The
      expression of MMP-2 greatly increased, and TIMP-2 decreased. Also, AGE, either in
      serum or in renal, the collagen IV, laminin, CTGF levels, and TGF-beta1 mRNA were
      reduced. Furthermore, both relative grades of mesangium hyperplasia by
      microscopical observation and the thickness of GBM by electron microscope
      measurement decreased significantly. CONCLUSION: GbE has protective effects on
      several pharmacological targets in the progress of DN and is a potential drug for
      the prevention of early DN.

PMID- 17506942
TI  - Effect of telmisartan on expression of protein kinase C-alpha in kidneys of
      diabetic mice.
AB  - AIM: To investigate the effects of angiotensin receptor blocker (ARB) telmisartan
      on the expression and distribution of protein kinase C (PKC)-alpha in the kidneys
      of diabetic mice. METHODS: Diabetic mice were induced with streptozotocin and a
      group of them were randomly selected for treatment with telmisartan. After 6
      weeks, the expression and localization of PKC-alpha in the renal cortex, and the
      outer and inner medulla were assessed by immunohistochemistry and
      semiquantitative Western blotting. In addition, expressions of PKC-alpha,
      transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth
      factor (VEGF) in glomeruli were measured by semiquantitative
      immunohistochemistry. RESULTS: Diabetic and normal mice showed similar
      distributions of PKC-alpha in the kidneys. The expression of PKC-alpha was found
      in glomeruli, epithelial cells of proximal tubules, and medullary-collecting
      duct, while not in the medullary and cortical thick ascending limb, and was
      different in the epithelial cells of proximal tubules of diabetic nephropathy
      (DN) mice, PKC-alpha was mostly translocated from the basement membrane to the
      apical membrane, whereas it was largely translocated from the apical membrane to
      the basement membrane in epithelial cells of the inner medullary-collecting duct.
      Western blotting detected increased expression of PKC-alpha in the renal cortex
      and outer medulla, but not in the inner medulla of DN mice. Enhanced expressions
      of PKC-alpha, TGF-beta1, and VEGF were shown in the glomeruli of DN mice, where
      PKC-alpha exhibited a correlation to VEGF, but no correlation to TGF-beta1. ARB
      telmisartan attenuated alterations of PKC-alpha as mentioned earlier in the DN
      mice. CONCLUSION: Our findings suggest that PKC-alpha may play a role in the
      pathogenesis of DN, and that the nephroprotective effects of ARB telmisartan may
      be partly associated with its influence on PKC-alpha.

PMID- 17506943
TI  - In vitro and in vivo induction of bone formation based on adeno-associated virus
      mediated BMP-7 gene therapy using human adipose-derived mesenchymal stem cells.
AB  - AIM: To determine whether adeno-associated virus (AAV)-2-mediated, bone
      morphogenetic protein (BMP)-7-expressing human adipose-derived mesenchymal stem
      cells (ADMS) cells would induce bone formation in vitro and in vivo. METHODS:
      ADMS cells were harvested from patients undergoing selective suction-assisted
      lipectomy and transduced with AAV carrying the human BMP-7 gene. Non-transduced
      cells and cells transduced with AAV serotype 2 carrying the enhanced green
      fluorescence protein gene served as controls. ADMS cells were qualitatively
      assessed for the production of BMP-7 and osteocalcin, and subjected to alkaline
      phosphatase (ALP) and Chinalizarin staining. A total of 2.5 x 10(6) cells mixed
      with type I collagen were implanted into the hind limb of severe combined immune
      deficient (SCID) mice and subjected to a histological analysis 3 weeks post
      implantation. RESULTS: Transfection of the ADMS cells achieved an efficiency of
      99% at d 7. Transduction with AAV2-BMP-7 induced the expression of BMP-7 until d
      56, which was markedly increased by d 7. The cells were positively stained for
      ALP. Osteocalcin production and matrix mineralization further confirmed that
      these cells differentiated into osteoblasts and induced bone formation in vitro.
      A histological examination demonstrated that implantation of BMP-7-expressing
      ADMS cells could induce new bone formation in vivo. CONCLUSION: The present in
      vitro and in vivo study demonstrated that human ADMS cells would be a promising
      source of autologous mesenchymal stem cells for BMP gene therapy and tissue
      engineering.

PMID- 17506944
TI  - Comparative proteomic analysis of human osteosarcoma and SV40-immortalized normal
      osteoblastic cell lines.
AB  - AIM: Comparative proteomics provide a powerful approach in screening for
      alterations in protein levels and post-translational modifications that are
      associated with tumors. In the present study, we aimed to identify candidate
      biomarkers to distinguish osteosarcoma (OS) cells from normal osteoblastic cells.
      METHODS: We employed 3 OS cell lines (U2OS, IOR/OS9, and SaOS-2), and used the
      SV40-immortalized normal osteoblastic cell line (hFOB1.19) as the control. The
      differential protein levels in OS and osteoblastic cells were identified using 2
      D gel electrophoresis followed by matrix-assisted laser desorption/ionization
      time of flight mass spectrometry analyses. Two proteins of interest, the levels
      of which were significantly increased in OS cells, were further characterized by
      Western blot analyses. RESULTS: Twenty-six proteins were identified, the
      expression level of which was either significantly increased or decreased in the
      OS cells as compared to the control cells. The expression level of the activator
      of 90 kDa shock protein ATPase homolog 1 (AHA1), was enhanced 12.4-, 24.1-, and
      23.8-fold in SaOS-2, IOR/OS9, and U2OS cells, respectively, and the level of the
      stomatin-like protein 2 (SLP-2) was increased by 10.4- and 7.8-fold in IOR/OS9
      and U2OS cells, respectively, as compared to normal osteoblastic cells. Those
      observations were confirmed by Western blot analyses. CONCLUSION: A differential
      proteomic analysis was successfully used to identify AHA1 and SLP-2 that were
      significantly overproduced in OS cells as compared to normal osteoblastic cells,
      suggesting that those proteins among others may be effective biomarker candidates
      for the identification of OS cells.

PMID- 17506945
TI  - Gene expression pattern in apoptotic QGY-7703 cells induced by homoharringtonine.
AB  - AIM: To classify the genes responsible for apoptosis in QGY-7703 cells induced by
      homoharringtonine (HHT). METHODS: Apoptosis in QGY-7703 cells induced by HHT was
      demonstrated by DNA fragmentation and morphological observation. cDNA microarray
      technology was used to detect gene transcription, and the result of microarrays
      for genes was confirmed by RT-PCR. RESULTS: Seventy-eight individual mRNA were
      identified and their transcription levels changed significantly. Those genes, of
      which 68% were upregulated and 32% were downregulated, were partially related to
      apoptosis. They were mostly oncogenes, tumor suppressors, enzymes, and kinases.
      CONCLUSION: HHT is a potential drug in the treatment of liver cancer. TGF-beta,
      TNF, FAS, p38MAPK, and p53 apoptosis signaling pathways were activated during
      apoptosis in QGY-7703 cells. Such inducible genes may play important roles in
      apoptosis and deserve to be further studied.

PMID- 17506946
TI  - Synergistic effect of combining paeonol and cisplatin on apoptotic induction of
      human hepatoma cell lines.
AB  - AIM: To investigate whether paeonol (Pae) has synergistic effects with cisplatin
      (CDDP) on the growth-inhibition and apoptosis-induction of human hepatoma cell
      lines HepG2 and SMMC-7721. METHODS: The cytotoxic effect of drugs was measured by
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The
      coefficient of drug interaction was used to analyze the nature of drug
      interactions. Morphological changes were observed by acridine orange fluorescence
      staining. Cell cycle and the apoptosis rate were detected by flow cytometry. Bcl
      2 and Bax expression were assayed by immunohistochemical staining. RESULTS: Pae
      or CDDP had antiproliferative effect on the 2 cell lines in a dose-dependent
      manner, with different sensitivities to drugs. More interestingly, a synergistic
      inhibitory effect on the viability of the 2 cell lines was observed after
      treatment with a combination of Pae (15.63, 31.25, and 62.5 mg/L) with various
      concentrations of CDDP. Further study showed typical morphological changes of
      apoptosis if the cells were exposed to the two agents for 24 h. The apoptotic
      rate of the cells with combination treatment was significantly higher than that
      of cells treated with Pae or CDDP alone. The expression of Bcl-2 decreased and
      that of Bax increased in the treated groups, especially in the combination group,
      with the ratio of Bcl-2/Bax decreasing correspondingly. Additionally, a
      combination of Pae with CDDP resulted in a stronger S phase arrest, compared with
      Pae or CDDP alone. CONCLUSION: Pae, in combination with CDDP, had a significantly
      synergistic growth-inhibitory and apoptosis-inducing effect on the 2 human
      hepatoma cell lines, which may be useful in hepatoma treatment.

PMID- 17506947
TI  - Upregulation of PTEN involved in rosiglitazone-induced apoptosis in human
      hepatocellular carcinoma cells.
AB  - AIM: To investigate the effects of rosiglitazone, a peroxisome proliferator
      activated receptor gamma (PPARgamma) agonist, on the expression of the
      phosphatase and tensin homologue deleted on chromosome 10 gene (PTEN) and cell
      growth in hepatocellular carcinoma cells, as well as the underlying mechanisms of
      these effects. METHODS: RT-PCR and Western blotting analyses were performed to
      detect transcription and the expression of PTEN in Hep3B cells treated with
      rosiglitazone. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      assay was used to evaluate cell growth. Flow cytometry, DNA fragmentation
      analysis, caspase enzymatic assay, and Hoechst 33258 staining were used to
      determine cell apoptosis. Furthermore, small interfering RNA was used to suppress
      PTEN expression. RESULTS: Rosiglitazone increased the expression of PTEN in a
      dose- and time-dependent manner through the PPARgamma-dependent signal
      transduction pathway. PTEN upregulation was concomitant with a decreased level of
      Akt phosphorylation, subsequently resulting in cell growth inhibition and
      apoptosis in Hep3B cells. PTEN knockdown dramatically blocked these effects of
      rosiglitazone. Moreover, the exposure of cells to rosiglitazone activated
      caspases-9 and -3 during apoptotic proceeding. CONCLUSION: Thus, upregulation of
      PTEN is involved in the inhibition of cell growth and the induction of cell
      apoptosis by rosiglitazone, suggesting that rosiglitazone may be useful in liver
      cancer therapy via apoptosis.

PMID- 17506948
TI  - Mitochondrial-derived ROS in edelfosine-induced apoptosis in yeasts and tumor
      cells.
AB  - AIM: To investigate whether a similar process mediates cytotoxicity of 1-O
      octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3, edelfosine) in
      both yeasts and human tumor cells. METHODS: A modified version of a previously
      described assay for the intracellular conversion of nitro blue tetrazolium to
      formazan by superoxide anion was used to measure the generation of reactive
      oxygen species (ROS). Apoptotic yeast cells were detected using terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. DNA
      fragmentation and the generation of ROS were measured by cytofluorimetric
      analysis in Jurkat cells. RESULTS: Edelfosine induced apoptosis in Saccharomyces
      cerevisiae, as assessed by TUNEL assay. Meanwhile, edelfosine induced a time- and
      concentration-dependent generation of ROS in yeasts. Rotenone, an inhibitor of
      the mitochondrial electron transport chain, prevented ROS generation and
      apoptosis in response to edelfosine in S cerevisiae. alpha-Tocopherol abrogated
      the edelfosine-induced generation of intracellular ROS and apoptosis. Edelfosine
      also induced an increase of ROS in human leukemic cells that preceded apoptosis.
      The overexpression of Bcl-2 by gene transfer abrogated both ROS generation and
      apoptosis induced by edelfosine in leukemic cells. Changes in the relative
      mitochondrial membrane potential were detected in both yeasts and Jurkat cells.
      CONCLUSION: These results indicate that edelfosine induces apoptosis in yeasts in
      addition to human tumor cells, and this apoptotic process involves mitochondria,
      likely through mitochondrial-derived ROS. These data also suggest that yeasts can
      be used as a suitable cell model in elucidating the antitumor mechanism of action
      of edelfosine.

PMID- 17506949
TI  - Overexpression of coxsackie and adenovirus receptor inhibit growth of human
      bladder cancer cell in vitro and in vivo.
AB  - AIM: To study the effect of the overexpression of coxsackie and the adenovirus
      receptor (CAR) on the growth of the human bladder cancer cell in vitro and in
      vivo. METHODS: A retroviral vector pLXSN-CAR expressing CAR was constructed and
      confirmed by restriction enzyme mapping. The pLXSN-CAR vector and control vector
      pLXSN were transfected into the PT67 packaging cell line to generate retrovirus
      with high titer. The CAR-negative T24 cell was infected with the pLXSN-CAR and
      the pLXSN retrovirus, respectively. The positive clone cells were selected with
      G418 for 2 weeks. The expression level of the CAR protein was detected by Western
      blot assay. T24 cell growth in vitro was determined by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Anchorage-independent growth was
      measured by soft-agar colony formation assay. In vivo cell growth was determined
      by a nude mice xenograft model. RESULTS: The pLXSN-CAR vector containing full
      length CAR cDNA was successfully constructed. Western blot analysis showed that a
      46 kDa specific band was found in pLXSN-CA-transfected T24 cells. MTT assay
      identified the growth inhibition of T24/pLXSN-CAR cells. The cell colony forming
      ability of T24/pLXSN-CAR cells was significantly lower than that of T24/pLXSN and
      parental T24 cells. There was a reduction in the tumor size in the T24/pLXSN-CAR
      group as compared with that of the T24/pLXSN group and parental T24 group.
      CONCLUSION: The overexpression of CAR in T24 bladder cancer cells can inhibit
      cell growth both in vitro and in vivo.

PMID- 17506950
TI  - Soluble components of Hericium erinaceum induce NK cell activation via production
      of interleukin-12 in mice splenocytes.
AB  - AIM: To investigate the immunoregulatory functions of water extracts of Hericium
      erinaceum (WEHE) focusing on natural killer (NK) cell-based anticancer
      activities. METHODS: Mouse splenocytes or purely isolated NK cells were
      stimulated with 1-100 mg/L WEHE for 24 h followed by co-culture with (51)Cr
      labeled Yac-1 cells for 4 h, then NK cell-derived cytolytic activity was measured
      using a radio-release assay. Neutralizing antibodies against mouse interleukin-12
      (IL-12) were added into the WEHE-stimulated splenocytes, thereafter, cytotoxicity
      was measured to examine the involvement of IL-12. RT-PCR and ELISA analyses were
      performed to confirm the induction of transcription and the translation of IL-12
      and interferon-gamma (IFN-gamma) in the WEHE-treated splenocytes. RESULTS: WEHE
      enhanced the cytolytic activity of total splenocytes towards Yac-1 cells in a
      dose-dependent manner. However, this activation was not observed when the NK
      cells isolated from the splenocytes were treated with WEHE. Furthermore, the
      treatment with antibodies against IL-12 abolished the effect of WEHE on
      splenocyte-derived cytolytic activity. RT-PCR and ELISA analyses showed the
      induction of IL-12 and IFN-gamma in the WEHE-treated splenocytes. CONCLUSION:
      WEHE indirectly activates the cytolytic ability of NK cells via the induction of
      IL-12 in total splenocytes, and possibly via other immuno-mediators or cellular
      components.

PMID- 17506951
TI  - Inhibitory effect of 1,8-cineol (eucalyptol) on Egr-1 expression in
      lipopolysaccharide-stimulated THP-1 cells.
AB  - AIM: To study the effects of 1,8-cineol (eucalyptol) on the expression of early
      growth response factor-1 (Egr-1) and NF-kappaB in the human monocyte THP-1 cell
      line stimulated by lipopolysaccharide (LPS). METHODS: The THP-1 cells were
      incubated with serial doses of 1,8-cineol (1, 10, and 100 mg/L, 30 min) before
      being stimulated with LPS (1 mg/L, 30 min). The localization of Egr-1 in the THP
      1 cells was detected by immunofluorescence and a laser scanning confocal
      microscope. The expression of Egr-1 in the nuclei and whole cell, and NF-kappaB
      in the nuclei, were measured by Western blot analysis. RESULTS: When stimulated
      by LPS, the FITC-labeled Egr-1 was detected mainly in the nuclei. Moreover, the
      expression of Egr-1 in the whole cell increased markedly compared with the
      control cells. 1,8-Cineol pretreatment decreased the expression of Egr-1 in both
      the nuclei and whole cell of the LPS-stimulated THP-1 cells, and this effect was
      concentration-dependent, but there was no reaction on the expression of NF-kappaB
      in the nuclei protein in the LPS-stimulated THP-1 cells. CONCLUSION: In a
      concentration-dependent manner, 1,8-Cineol reduces LPS-induced Egr-1 expression
      in nuclei and in whole cell of THP-1 cells, but shows no effect on NF-kappaB
      expression.

PMID- 17506952
TI  - FG020326-loaded nanoparticle with PEG and PDLLA improved pharmacodynamics of
      reversing multidrug resistance in vitro and in vivo.
AB  - AIM: FG020326, a novel imidazole derivative, is a potent multidrug-resistance
      (MDR) modulator in vitro and in vivo. However, FG020326 is insoluble. PEDLLA
      FG020326 is a FG020326-loaded nanoparticle formed with diblock copolymers of poly
      (ethylene glycol)-block-poly (D,L-lactic acid) (PEG:PDLLA, PEDLLA) that can
      solubilize FG020326. This work was intended to evaluate the pharmacodynamics of
      PEDLLA-FG020326 on reversing MDR in vitro and in vivo. METHODS: Cytotoxicity was
      determined by tetrazolium assay. The intracellular accumulation and efflux of
      doxorubicin (Dox) were detected by fluorescence spectrophotometry. The function
      of P-glycoprotein was examined by Rhodamine 123 (Rh123) accumulation detected by
      flow cytometry. The KBv200 cell xenograft model was established to investigate
      the effect of PEDLLA-FG020326 on reversing MDR in vivo. RESULTS: PEDLLA-FG020326
      and FG020326 exhibited 56.4- and 35.9-fold activity in reversing KBv200 cells to
      vincristine (VCR) resistance, respectively and 14.98- and 7.64-fold to Dox
      resistance, respectively. PEDLLA-FG020326 was much stronger than FG020326,
      resulting in the increase of Dox and Rh123 accumulation and the decrease of
      intracellular Dox extrusion in KBv200 cells. Importantly, PEDLLA-FG020326
      exhibited more powerful activity than FG020326 in enhancing the effect of VCR
      against KBv200 cell xenografts in nude mice, but did not appear more toxic.
      CONCLUSION: The pharmacodynamics of FG020326 was improved by incorporating it
      into a micellar nanoparticle formed with PEG-block-PDLLA copolymers.

PMID- 17506953
TI  - [Vascular malformations (II). Diagnosis, pathology and treatment].
AB  - Diagnosis of vascular malformations is essentially clinical, based on the
      evolution and morphology of lesions. A biopsy is rarely needed to evaluate the
      nature of the vessels. Imaging examinations are necessary to assess the extension
      of malformations as well as the osteomuscular and visceral compromise. New
      techniques such as 3D angio-CT scan and angio-MRI improve the diagnosis of some
      vascular malformations, especially the large combined ones such as Klippel
      Trenaunay syndrome, thus limiting the need for invasive procedures. On the other
      hand, the advances in laser technology, particularly pulsed dye laser for port
      wine stains and Nd:YAG laser for superficial venous malformations constitute new
      alternatives for the management of these patients. Other emergent treatments
      include microfoam sclerotherapy for venous and combined, slow-flow malformations,
      and new embolizing materials associated to surgery for arterio-venous
      malformations. The second part of this review is focused on the complementary
      diagnosis (imaging exams, pathology and accessory tests) and multidisciplinary
      and specific treatment based on the different groups.

PMID- 17506954
TI  - [Should benign and trivial cutaneous lesions be treated in the Public Health
      System?].

PMID- 17506955
TI  - [Practical management of C1 inhibitor deficiency].
AB  - C1 inhibitor deficiency is a rare syndrome clinically characterized by recurrent
      episodes of swelling of subcutaneous tissue or angioedema. It can involve the
      skin, upper respiratory airways and abdomen. There are two main types: hereditary
      and acquired. Angioedema can involve practically any part of the cutaneous
      surface, it can cause lethal laryngeal edema and can present as gastrointestinal
      obstruction. The attacks can be triggered, in general, by trauma, drugs or
      infections. Diagnosis is confirmed by decreased serum levels of C4 and absence or
      marked decrease of the level or function of C1 inhibitor. Commonly employed drugs
      for prophylaxis and treatment of these patients include anabolic steroids,
      antifibrinolytic agents, and infusion of C1 inhibitor concentrate. Fresh frozen
      plasma is an option to be considered for short term prophylaxis or treatment of
      the acute attack. It is convenient to know this syndrome as it is a potentially
      life-threatening disease. Diagnosis of this rare syndrome is based on clinical
      features and characteristic alterations of laboratory tests. The acute attack
      should be treated as quickly as possible. Prophylactic therapy is indicated in
      certain circumstances (dental procedures, oral surgery).

PMID- 17506956
TI  - [Observational study to evaluate the impact of an educational/informative
      intervention in the emotional status (anxiety) of patients with atopic dermatitis
      (CUIDA-DEL)].
AB  - INTRODUCTION: One of the first therapeutic measures in atopic dermatitis should
      be the educational and informative approach about prophylactic aspects and
      evolution of the disease. This type of proceedings has been shown to be
      beneficial for the anxious type of emotional status in patients with atopic
      dermatitis. We evaluated the impact of an educational/informative intervention in
      the emotional status (anxiety) of patients with atopic dermatitis in Spain.
      MATERIAL AND METHODS: Investigators were randomized into two study groups: the
      control group (CG) that followed current clinical practice and the intervention
      group (IG) that handed patients, in each visit, a booklet of information about
      different prophylactic aspects and care of atopic dermatitis. The duration of the
      study was 6 months with quarterly visits. All included patients had a diagnosis
      of atopic dermatitis. Anxiety was evaluated with the STAI anxiety questionnaire
      and clinical data regarding dermatological aspects (IGA, pruritus scale, location
      of the lesions) were also recorded. RESULTS: A total of 1,247 patients were
      recruited thanks to the collaboration of 158 investigators. Patients were
      distributed as follows: 683 (54.7 %) in the CG and 564 (45.2 %) in the IG. Both
      group were homogeneous with respect to basal characteristics, and were
      constituted by 54 % of women with a mean age of 19 years. Eighty-six percent of
      atopic dermatitis lesions were preferentially located in extremities. Patients of
      both study groups showed improvement in their emotional status (trait and state
      anxiety) throughout the study with significant decreases in the STAI scores
      compared to basal ones. Regarding improvement in the questionnaire scores, no
      significant differences were observed between groups except in children aged 9 to
      15 years, in the pediatric version of the STAI trait where the percentage of
      score decrease at 6 months adjusted to the basal score was 5.5 (19.0) for the CG
      and 10.6 (18.9) for the IG, (p < 0.05). A higher percentage of patients finished
      the study in the IG compared to the CG (83.1 % vs. 76.1 % p < 0.005). DISCUSSION
      AND CONCLUSIONS: Although patients in the IG showed greater compliance with the
      follow-up of the study, the informative intervention about prophylactic aspects
      of atopic dermatitis designed in this study does not appear to have had an impact
      in improving the emotional status of adult patients.

PMID- 17506957
TI  - [Narrow band UVB therapy in early stage mycosis fungoides. A study of 23
      patients].
AB  - INTRODUCTION: Phototherapy is effective for mycosis fungoides. Narrow band UVB
      (UVB1) therapy is being used as an alternative to PUVA therapy for its efficacy
      and less adverse events. The objective of the study was to determine the efficacy
      of narrow band UVB therapy in early stage mycosis fungoides. METHODS: It is a
      retrospective study of 23 patients with stage IB mycosis fungoides that have
      received UVB1 therapy following the phototherapy protocol of the Spanish
      Photobiology Group. RESULTS: Thirteen patients (57 %) had a complete response,
      eight patients (35 %) had a partial response and two patients (8 %) did not
      respond. Half of the patients with complete response (n = 6) relapsed after one
      year of follow-up. CONCLUSIONS: We consider that UVB1 therapy is a good
      alternative for treatment of early stage mycosis fungoides, although the disease
      free period is short.

PMID- 17506958
TI  - [Oral involvement in lymphomatoid papulosis].
AB  - Lymphomatoid papulosis is a cutaneous lymphoma with an indolent clinical
      behaviour characterized by chronic development of recurrent, self-limited lesions
      appearing as necrotic papules and with a pathology compatible with T cell
      lymphoma. Mucosal involvement by lymphomatoid papulosis is very rare but has been
      reported in the literature. It usually appears as ulcers in patients previously
      diagnosed of lymphomatoid papulosis. From a histological perspective it is
      characterized by an infiltrate of CD 30 positive atypical lymphocytes together
      with a mixed inflammatory infiltrate of eosinophils, neutrophils, histiocytes and
      plasma cells. We report the case of a man previously diagnosed of lymphomatoid
      papulosis that developed two ulcerated lesions in the tongue whose biopsy
      confirmed the diagnosis of oral involvement by lymphomatoid papulosis.

PMID- 17506959
TI  - [Bilateral pseudo-Kaposi sarcoma in upper limbs].
AB  - Acroangiodermatitis or pseudo-Kaposi sarcoma is an angioproliferative, self
      limited entity that includes a group of diseases, congenital or acquired, with
      cutaneous lesions similar to Kaposi sarcoma (KS). This term can lead to confusion
      because it comprises several entities that are completely different, nonetheless,
      it has an important clinical value as it guides the diagnosis and management of
      these patients. We report the case of a 67-year-old patient with lesions of
      acroangiodermatitis in both forearms secondary to arteriovenous shunts from
      hemodialysis. Doppler ultrasound showed a former arteriovenous fistula in
      addition to the one already known. Immunohistochemical study showed CD34+
      staining in endotelial cells and absence of HHV-8 expression.

PMID- 17506960
TI  - [Cutaneous adverse reaction to Bio-Alcamid implant].
AB  - In the last years new and numerous materials for the correction of defects and
      wrinkles have been developed. One of these materials is Bio-Alcamid, a non
      reabsorbable gel polymer constituted by meshes of poly-alkyl-imide, without known
      adverse effects. We report a 34-year-old woman that had Bio-Alcamid implants for
      acne scars and several months after presented nodular lesions together with a
      painful inflammatory nodule. The nodule was drained and culture of the purulent
      material yielded Streptococcus viridans. A cytology and a cellular block of that
      material showed a granulomatous inflammatory reaction together with a foreign
      body. The different types of reactions to implants and their pathogenic mechanism
      are discussed. It is important to know these possible reactions to filler
      materials given their increasing use and the potential medico-legal consequences.

PMID- 17506962
TI  - [Ulcers in a patient with chronic lymphocytic leukemia].

PMID- 17506961
TI  - [Primary cutaneous aspergillosis in a leukemic child].
AB  - Primary cutaneous aspergillosis is a rare cutaneous disease that usually affects
      immunodepressed patients of any age. The most common associated disorders in
      children are leukemias and lymphomas although it can also occur in neonates and
      preterms due to their intrinsic immunological immaturity. We report the case of a
      4-year-old boy diagnosed of acute lymphoblastic leukemia that, during
      chemotherapy, developed an ulceronecrotic inflammatory cutaneous lesion in the
      venopuncture area of the left forearm, and whose microbiological culture was
      positive for Aspergillus flavus.

PMID- 17506963
TI  - [Violaceus plaque in the left leg].

PMID- 17506964
TI  - [Linear basal cell carcinoma. Report of two cases].

PMID- 17506965
TI  - [Asymptomatic digital angioleiomyoma].

PMID- 17506966
TI  - [Cutaneous chloromas as the presenting feature of acute myeloid leukemia in a
      child].

PMID- 17506967
TI  - [Effectiveness of topical application of nitroglycerin spray to increase survival
      of cutaneous flaps and grafts].

PMID- 17506968
TI  - Vesicular stomatitis New Jersey virus (VSNJV) infects keratinocytes and is
      restricted to lesion sites and local lymph nodes in the bovine, a natural host.
AB  - Inoculation of vesicular stomatitis New Jersey virus (VSNJV) by skin
      scarification of the coronary-band in cattle, a natural host of VSNJV, resulted
      in vesicular lesions and 6-8 log(10) TCID(50) increase in skin virus titers over
      a 72 h period. Virus infection was restricted to the lesion sites and lymph nodes
      draining those areas but no virus or viral RNA was found in the blood or in 20
      other organs and tissues sampled at necropsy. Scarification of flank skin did not
      result in lesions or a significant increase in viral titer indicating that viral
      clinical infection is restricted to skin inoculation at sites where lesions
      naturally occur. Viral antigens co-localized primarily with keratinocytes in the
      coronary band, suggesting these cells are the primary site of viral replication.
      Viral antigen also co-localized with few MHC-II positive cells, but no co
      localization was observed in cells positive for macrophage markers. Although
      granulocyte infiltration was observed in lesions, little viral antigen co
      localized with these cells. This is the first detailed description of VSNJV
      tissue distribution and infected cell characterization in a natural host. The
      pathogenesis model shown herein could be useful for in-vivo tracking of virus
      infection and local immune responses.

PMID- 17506969
TI  - Diversity of Mycoplasma hyopneumoniae in pig farms revealed by direct molecular
      typing of clinical material.
AB  - Mycoplasma hyopneumoniae is the etiological agent of enzootic pneumonia in swine.
      Various reports indicate that different strains are circulating in the swine
      population. We investigated the variety of M. hyopneumoniae strains by a newly
      developed genetic typing method based on the polyserine repeat motif of the LppS
      homolog P146. PCR amplification using M. hyopneumoniae specific, conserved
      primers flanking the region encoding the repeat motif, followed by sequencing and
      cluster analysis was carried out. The study included strains isolated from
      different geographic regions as well as lysates from lung swabs from a series of
      pig farms in Switzerland. High diversity of M. hyopneumoniae was observed but
      farms being in close geographic or operative contact generally seemed to be
      affected by the same strains. Moreover, analysis of multiple samples from single
      pig farms indicated that these harbored the same, farm-specific strain. The
      results indicate that multiple strains of M. hyopneumoniae are found in the swine
      population but that specific strains or clones are responsible for local
      outbreaks. The method presented is a highly reproducible epidemiologic tool
      allowing direct typing of M. hyopneumoniae from clinical material without prior
      isolation and cultivation of strains.

PMID- 17506970
TI  - Tritrichomonas foetus damages bovine oocytes in vitro.
AB  - Tritrichomonas foetus is an extracellular parasite of the urogenital tract in
      cattle. It causes infertility and abortion, but there is no documented
      information on the susceptibility of bovine oocytes to the parasite, except by
      one article that claimed no effects of T. foetus on oocytes or embryos. The aim
      of the present study was to study the effects provoked by T. foetus when in
      interaction with bovine oocytes. Oocytes were obtained from cow ovaries and
      divided into two groups: (1) one group contained cumulus cells, whereas (2) a
      second group was denuded from these cells. Light microscopy, video microscopy and
      scanning electron microscopy (SEM) revealed that exposure of oocytes to T. foetus
      caused rapid adhesion of the trichomonads to cumulus cells and to the zona
      pellucida (ZP). Motile parasites were observed for 12 h. The ZP was completely
      damaged, and the parasites were able to infiltrate beneath the ZP and reached the
      oocytes directly when the oocytes were denuded of the cumulus cells. Both the
      oocytes and the cumulus cells exhibited morphological characteristics compatible
      with apoptosis after interaction with T. foetus, such as chromatin condensation,
      the presence of several cytoplasmic vacuoles, with intact cellular membranes and
      organelles. The results from this study demonstrate that when a large number of
      T. foetus interacts with oocytes in vitro damage and apoptosis are provoked in
      the cow's reproductive cells. The behavior of this parasite as one of the causes
      of cattle infertility is discussed.

PMID- 17506971
TI  - BSE, feed and cattle in Switzerland: is there a spatial relation?
AB  - Cross-contamination of cattle feed with meat and bone meal (MBM) allowed in feed
      for other species is regarded as the current hypothesis for the infection pathway
      of Bovine Spongiform Encephalopathy (BSE) cases occurring after the
      implementation of a ban on feeding MBM to cattle. This study was aimed at
      establishing a spatial relation between BSE cases in Switzerland and the findings
      of MBM in cattle feed. A cluster analysis and a cohort study were performed. Two
      hundred sixteen BSE cases born after December 1990 and detected until August 1st
      2005, screening data of 504 feed producers between 1996 and 2001 and population
      data from the Swiss 2001 cattle census were included. The cluster analysis showed
      feed producer, positive for MBM contaminations in cattle feed, as possible
      cluster centres for BSE cases. In the cohort study, farms within a radius of 2
      and 10 km around positive feed producers showed significantly higher odds to have
      a BSE case than the control group. The odds ratio and its 95% confidence interval
      were 2.23 (1.26-3.93) for the 2 km radius and 1.38 (1-1.9) for the 10 km radius.
      The results provide evidence for a spatial relation between cross-contamination
      and BSE occurrence. These findings support the hypothesis of cross-contamination
      to be an important route for BSE transmission after a feed ban.

PMID- 17506972
TI  - A full UL13 open reading frame in Marek's disease virus (MDV) is dispensable for
      tumor formation and feather follicle tropism and cannot restore horizontal virus
      transmission of rRB-1B in vivo.
AB  - Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that is highly
      contagious in poultry. Recombinant RB-1B (rRB-1B) reconstituted from an
      infectious genome cloned as a bacterial artificial chromosome (BAC) is unable to
      spread horizontally, quite in contrast to parental RB-1B. This finding suggests
      the presence of one or several mutations in cloned relative to parental viral
      DNA. Sequence analyses of the pRB-1B bacmid identified a one-nucleotide insertion
      in the UL13 orthologous gene that causes a frame-shift mutation and thereby
      results in a theoretical truncated UL13 protein (176 aa vs. 513 aa in parental RB
      1B). UL13 genes are conserved among alphaherpesviruses and encode protein
      kinases. Using two-step "en passant" mutagenesis, we restored the UL13 ORF in pRB
      1B. After transfection of UL13-positive pRB-1B DNA (pRB-1B*UL13), the resulting,
      repaired virus did not exhibit a difference in cell-to cell spread (measured by
      plaque sizes) and in UL13 transcripts in culture compared to parental rRB-1B
      virus. Although 89% of the chickens inoculated with rRB-1B*UL13 virus developed
      tumors in visceral organs, none of the contact birds did. MDV antigens were
      clearly expressed in the feather tips of rRB-1B infected chickens, suggesting
      that the UL13 gene mutation did not alter virus tropism of the feather follicle.
      The results indicate that the correction in UL13 gene alone is not sufficient to
      restore in vivo spreading capabilities of the rRB-1B virus, and that other
      region(s) of pRB-1B might be involved in the loss-of-function phenotype. This
      finding also shows for the first time that a full UL13 ORF is dispensable for MDV
      tumor formation and feather follicle tropism.

PMID- 17506973
TI  - Identification and heterologous expression of a Sarcoptes scabiei cDNA encoding a
      structural antigen with immunodiagnostic potential.
AB  - The mite Sarcoptes scabiei causes sarcoptic mange (or scabies), a disease of
      considerable human and veterinary significance. An S. scabiei cDNA clone of about
      2 kb was isolated from a S. scabiei var. hominis expression library by
      immunological screening using blood serum from a naturally infected chamois
      (Rupicapra rupicapra). The nucleotide sequence of the identified cDNA contains an
      open reading frame of 1930 bp that encodes a 642 amino acid polypeptide. This
      polypeptide shows tandem repeats of a glycine-serine rich 20 residue sequence
      followed by a unique C-terminal glutamate rich 54 residue sequence. The cDNA or
      the deduced polypeptide did not show significant similarities to any of the
      sequences in the databases. A carboxyl-terminal fragment of this polypeptide
      (residues 380 to 642) was efficiently expressed in Escherichia coli as a fusion
      with Glutathione S-transferase and then was used to produce a specific antiserum.
      The antigen encoded by the cDNA was located at the integument of the mite's
      epidermis and the cavities surrounding its vital organs. Western blot analysis of
      mite extracts using the specific antiserum against the recombinant protein
      identified antigens larger that 60 kDa indicating that the isolated cDNA did not
      contain the full ORF. Moreover, we designed a diagnostic assay based on the
      carboxyl-terminal fragment of the antigen for the identification of infected
      animals.

PMID- 17506974
TI  - Natural infection of cattle with an atypical 'HoBi'-like pestivirus--implications
      for BVD control and for the safety of biological products.
AB  - During a study on Bovine Viral Diarrhoea (BVD) epidemiology in Thailand, a
      pestivirus was detected in serum from a calf. Comparative nucleotide sequence
      analysis showed that this virus was closely related to a recently described
      atypical pestivirus (D32/00_'HoBi') that was first isolated from a batch of
      foetal calf serum collected in Brazil. The results from virus neutralisation
      tests performed on sera collected from cattle in the herd of the infected calf,
      showed that these cattle had markedly higher antibody titres against the atypical
      pestivirus 'HoBi' than against Bovine Viral Diarrhoea Virus types 1 and 2, or
      Border Disease Virus. The results also supported, consequently, the results from
      the molecular analysis, and demonstrated that a 'HoBi'-like pestivirus had been
      introduced to, and was now circulating in the herd. This study is the first to
      report a natural infection in cattle with a virus related to this atypical
      pestivirus, and it suggests that this group of pestiviruses may already be spread
      in cattle populations. The findings have implications for BVD control and for the
      biosafety of vaccines and other biological products produced with foetal calf
      serum. Consequently, these atypical pestiviruses should be included in
      serological assays, and any diagnostic assay aimed at detection of pestiviruses
      in biological products or animals should be tested for its ability to detect
      them.

PMID- 17506975
TI  - Intervention practices in musculoskeletal disorder prevention: a critical
      literature review.
AB  - Musculoskeletal disorders (MSDs) affect much of the workforce and remain a major
      form of occupational ill health. With a view to improving the efficacy of
      interventions, this review examined preventative actions relating to these
      disorders. A detailed analysis grid was used to classify the information
      contained in the 47 reviewed articles whose common aspect was to report actions
      carried out in the workplace that led to the implementation of changes to prevent
      MSDs. The analysis identified and characterized three major categories of
      intervention processes in MSD prevention: the complete type (n=17), the shortened
      type (n=16), and the turnkey type (n=14). These three groups of intervention
      processes were differentiated by their approaches and their contexts of
      application. The result was important differences in the changes implemented.
      Because of the variability in intervention processes and possible impacts on MSD
      prevention, a proposal to "delimit" these processes so as to improve their
      effectiveness is presented.

PMID- 17506976
TI  - Datalink in air traffic management: Human factors issues in communications.
AB  - This paper examines issues underpinning the potential move in aviation away from
      real speech radiotelephony (R/T) communications towards datalink communications
      involving text and synthetic speech communications. Using a novel air traffic
      control (ATC) task, two experiments are reported. Experiment 1 compared the use
      of speech and text while Experiment 2 compared the use of real and synthetic
      speech communications. Results indicated that generally there were no significant
      differences between speech and text communications and that either type could be
      used without any main effects on performance. However, a number of specific
      differences were observed across the different phases of the scenarios indicating
      that workload levels may be more varied when speech communications are used.
      Experiment 2 illustrated that participants placed a greater level of trust in
      real speech than synthetic speech, and trusted true communications more than
      false communications (regardless of whether they were real or synthetic voices).
      The findings are considered in terms of datalink initiatives for future air
      traffic management, the importance placed on real speech R/T communications, and
      the need to develop more natural synthetic speech in this application area.

PMID- 17506977
TI  - Comparative transport efficiencies of urea analogues through urea transporter UT
      B.
AB  - Expression of urea transporter UT-B confers high urea permeability to mammalian
      erythrocytes. Erythrocyte membranes also permeate various urea analogues,
      suggesting common transport pathways for urea and structurally similar solutes.
      In this study, we examined UT-B-facilitated passage of urea analogues and other
      neutral small solutes by comparing transport properties of wildtype to UT-B
      deficient mouse erythrocytes. Stopped-flow light-scattering measurements
      indicated high UT-B permeability to urea and chemical analogues formamide,
      acetamide, methylurea, methylformamide, ammonium carbamate, and acrylamide, each
      with P(s)>5.0 x 10(-6) cm/s at 10 degrees C. UT-B genetic knockout and phloretin
      treatment of wildtype erythrocytes similarly reduced urea analogue
      permeabilities. Strong temperature dependencies of formamide, acetamide,
      acrylamide and butyramide transport across UT-B-null membranes (E(a)>10 kcal/mol)
      suggested efficient diffusion of these amides across lipid bilayers. Urea
      analogues dimethylurea, acryalmide, methylurea, thiourea and methylformamide
      inhibited UT-B-mediated urea transport by >60% in the absence of transmembrane
      analogue gradients, supporting a pore-blocking mechanism of UT-B inhibition.
      Differential transport efficiencies of urea and its analogues through UT-B
      provide insight into chemical interactions between neutral solutes and the UT-B
      pore.

PMID- 17506978
TI  - Rumination and overgeneral autobiographical memory.
AB  - Two studies investigated the effects of rumination on the retrieval of
      autobiographical memories in high-depressed and low-depressed individuals.
      Experiment 1 administered either a rumination or distraction task prior to a cued
      autobiographical memory task. High-depressed participants recalled more
      overgeneral memories following rumination relative to distraction, whereas
      experimental inductions did not influence low-depressed participants. Experiment
      2 administered either a positive or negative rumination task prior to a cued
      autobiographical memory task. Negatively valenced rumination led high-depressed
      participants to recall more overgeneral memories than positively valenced
      rumination; this effect was not observed in low-depressed participants. These
      findings accord with the proposal that rumination is a mediating mechanism in the
      retrieval of overgeneral memories, and extends this proposal by indicating that
      negatively valenced ruminative content is particularly instrumental in inducing
      overgeneral retrieval.

PMID- 17506979
TI  - Foxc2 induces expression of MyoD and differentiation of the mouse myoblast cell
      line C2C12.
AB  - The Fox family of transcription factors is expressed in various organs and
      tissues during development, and is involved in a variety of developmental and
      cellular differentiation processes. Foxc2 mRNA is strongly expressed in mesoderm
      derived tissues in the embryo, but the molecular mechanism of Foxc2-induced
      cellular differentiation and the physiological role of Foxc2 are unclear. In
      mouse myoblast C2C12 cells, over-expression of Foxc2 increased the expression of
      desmin, the muscle-specific member of the intermediate filament family of
      proteins, and induced the synthesis of myotubes. Transient expression of Foxc2
      increased MyoD mRNA and protein levels, as assessed by real-time PCR and Western
      blot, respectively. Chromatin immunoprecipitation (ChIP) analysis showed that
      Foxc2 does not bind to the promoter region of the MyoD gene, which indicated that
      Foxc2 does not directly activate MyoD. In contrast to reports that Foxc2
      regulates the production of basement membrane components in endothelial cells, we
      found no evidence of Foxc2-mediated regulation of Collagen type IV alpha 1
      (Col4a1) or Col4a2 in myoblast cells. Taken together, these results indicate that
      Foxc2 plays an important role in the development of the mesenchyme through the
      regulation of MyoD gene expression.

PMID- 17506980
TI  - Swings in blood glucose levels accelerate atherogenesis in apolipoprotein E
      deficient mice.
AB  - The aim of this study was to investigate the effect of fluctuations in blood
      glucose levels on atherogenesis. Apolipoprotein (apo) E-deficient mice fed
      maltose twice daily were used as a model of repetitive postprandial glucose
      spikes. We investigated the number of macrophages adherent to the endothelium and
      the area of fibrotic arteriosclerotic lesions, with and without administration of
      miglitol, an alpha-glucosidase inhibitor. Macrophage adhesion to endothelial
      cells in thoracic aorta was quantitated by the en face method for optimal
      observation of endothelial surface after immunohistochemical staining for Mac-2.
      The area of arteriosclerotic lesions was measured in elastica van Giesson-stained
      proximal aorta. The number of adherent macrophages increased at 1 week after
      commencement of maltose feeding and the size of arteriosclerotic lesion increased
      at 5 weeks after such feeding. These increases were prevented by simultaneous use
      of miglitol. Our data demonstrated that glucose fluctuations accelerate
      atherogenesis. This was independent of changes in serum cholesterol level in
      vivo. Reduction of glucose fluctuation by alpha-glucosidase inhibitor efficiently
      controlled the progression of atherosclerosis.

PMID- 17506981
TI  - Integrative analysis and validation of robust gene signature in lung cancer.
AB  - We studied robust gene signature (RGS) in lung cancer by using an approach of
      integrating a highly diverse collection of cancer genome-wide datasets, which
      were six public microarray datasets, one pair of Suppression Subtractive
      Hybridization EST library, one pair of Serial Analysis of Gene Expression (SAGE)
      experiments, and 191 Loss of Heterozygosity (LOH) reports obtained from 388
      publications. Among the 109 RGS genes identified from our study, 14 of the 15
      reported differentially expressed genes (DEGs) based on literature verification
      were consistent with our predictions. Out of the remaining 94 genes that were not
      reported as DEGs in lung cancer by any publication, we randomly picked eight and
      verified their expression in lung cancer versus normal tissues by semi
      quantitative RT-PCR amplification, and all showed consistent expression pattern
      with our findings. System assessment analysis revealed that our integrative
      method had an accuracy of 95% and a correlation coefficients value of 0.92.

PMID- 17506982
TI  - A fused selenium-containing protein with both GPx and SOD activities.
AB  - As a safeguard against oxidative stress, the balance between the main antioxidant
      enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), and
      catalase (CAT) was believed to be more important than any single one, for
      example, dual-functional SOD/CAT enzyme has been proved to have better
      antioxidant ability than either single enzyme. By combining traditional fusion
      protein technology with amino acid auxotrophic expression system, we generated a
      bifunctional enzyme with both GPx and SOD activities. It displayed better
      antioxidant ability than GPx or SOD. Such dual-functional enzymes could
      facilitate further studies of the cooperation of GPx and SOD and generation of
      better therapeutic agents.

PMID- 17506983
TI  - Modulation of T-type Ca2+ channels by corticotropin-releasing factor through
      protein kinase C pathway in MN9D dopaminergic cells.
AB  - Corticotrophin-releasing factor (CRF) is the main regulator of the body's stress
      axis and its signal is translated through G-protein-coupled CRF receptors (CRF
      R1, CRF-R2). Even though CRF receptors are present in the midbrain dopamine
      neurons, the cellular mechanism of CRF action is not clear yet. Since voltage
      dependent Ca(2+) channels are highly expressed and important in dopamine neuronal
      functions, we tested the effect of CRF on voltage-dependent Ca(2+) channels in
      MN9D cells, a model of dopamine neurons. The application of CRF-related peptide,
      urocortin 1, reversibly inhibited T-type Ca(2+) currents, which was a major
      Ca(2+) channel in the cells. The effect of urocortin was abolished by specific
      CRF-R1 antagonist and was mimicked by protein kinase C (PKC) activator, phorbol
      12-myristate 13-acetate. PKC inhibitors abolished the effect of urocortin. These
      results suggest that urocortin modulates T-type Ca(2+) channel by interacting
      with CRF-R1 via the activation of PKC signal pathway in MN9D cells.

PMID- 17506984
TI  - Midkine as a novel target for antibody therapy in osteosarcoma.
AB  - Osteosarcoma is a malignant tumor with poor prognosis, and lack of accurate
      prognostic factors is one of the reasons that make this tumor difficult to cure.
      The heparin-binding growth factor, midkine is involved in generation and
      progression of many types of tumors. However, the relationship between midkine
      and osteosarcoma has been unclear. We show here that midkine is overexpressed in
      osteosarcoma and the level of midkine expression is correlated with prognosis
      (P<0.05; log-rank test). Treatment with functional antibodies against midkine
      suppresses growth of osteosarcoma cell lines, 9N2, 3N1, Saos-2, and NOS-1, to 25
      65% of untreated controls. Our results suggest that midkine is useful as a
      prognostic marker, and is a candidate therapeutic target for osetosarcomas.

PMID- 17506985
TI  - Mulberry leaf powder prevents atherosclerosis in apolipoprotein E-deficient mice.
AB  - Mulberry is commonly used to feed silkworms. Here we examined whether a dietary
      intake of mulberry leaf (ML) could affect atherogenesis in vivo and in vitro.
      Apolipoprotein E-deficient mice were fed either normal chow (control group) or a
      diet containing 1% ML powder (ML group) from 6 weeks of age. The mice were
      sacrificed after 12 weeks. The susceptibility of plasma lipoprotein to oxidation
      was assessed using diene formation. A significant increase in the lag time of
      lipoprotein oxidation was detected in the ML group compared with the control
      group. Furthermore, the ML group showed a 40% reduction in atherosclerotic lesion
      size in the aortae compared with the control. We also examined the direct anti
      oxidative activity of ML in vitro. Aqueous extract of ML had a strong scavenging
      effect on 1,1-diphenyl-2-picrylhydrazyl and inhibited lipoprotein oxidation.
      These results confirm that ML contains anti-oxidative substances that might help
      prevent atherosclerosis.

PMID- 17506986
TI  - Differential intra-proteasome interactions involving standard and immunosubunits.
AB  - Animals with immune systems have two types of proteasomes, "standard proteasomes"
      and "immunoproteasomes" that respectively contain constitutively expressed
      catalytic subunits or interferon-gamma-inducible catalytic subunits.
      Interestingly, proteasome assembly is biased against formation of most mixed
      proteasomes containing combinations of standard subunits and immunosubunits. We
      previously demonstrated that catalytic subunit propeptide differences contribute
      to this assembly specificity. In the current study, we investigated the
      contributions of catalytic subunit propeptides and C-terminal extensions to intra
      proteasome protein-protein interactions that are potentially involved in
      mediating biased assembly of human proteasomes, and we found a number of
      interactions that differentially depended on these structures. For example, the C
      terminal extension of standard subunit beta2 is required for beta2's interaction
      with adjacent beta3, whereas the C-terminal extension of immunosubunit beta2i is
      dispensable for beta2i's interaction with beta3. Taken together, our results
      suggest mechanisms whereby differential intra-proteasome interactions could
      contribute to proteasome assembly specificity.

PMID- 17506987
TI  - Upregulated expression of postsynaptic density-93 and N-methyl-D-aspartate
      receptors subunits 2B mRNA in temporal lobe tissue of epilepsy.
AB  - OBJECTIVE: To investigate the expression of PSD-93 mRNA and NR2B mRNA in the
      brain tissue from the patients with epilepsy so as to explore the possible
      mechanisms of the pathogenesis of the epilepsy. METHODS: Fifty-six patients with
      epilepsy were divided into intractable epilepsy (IE) and non-intractable epilepsy
      (NIE) groups. cDNA microarrays prepared from the brain tissues obtained from
      these two groups were scanned and comparison to those from the non-epileptogenic
      control (C) was made. Expression level of PSD-93mRNA and NR2BmRNA were examined
      by reverse transcription polymerase chain reaction (GAPDH gene, internal
      control). Expression ratio (target gene/GAPDH) was used to evaluate each gene
      relative expression level. RESULTS: The cDNA microarray analysis showed that the
      expression of PSD-93 mRNA related to the function of NMDAR-NO signal transduction
      pathway was significantly higher in epilepsy patients than those in the
      controlled group. The results of RT-PCR were consistent with those of the cDNA
      microarrays. The relative expression ratio of PSD-93 in patients with non
      epileptogenic control, NIE, and IE was 0.159, 0.368, and 0.341, respectively.
      Correspondingly, that of NR2B was 0.198, 0.738, and 0.903, respectively. The
      expressions of PSD-93 and NR2B in the NIE and IE were significantly higher than
      those of control, respectively (P<0.05). However, there was no significantly
      difference the expression of PSD-93 between NIE and IE. (P>0.05), neither do that
      of NR2B (P>0.05). CONCLUSIONS: The upregulated expressions of PSD-93 mRNA and
      NR2BmRNA may be involved in the pathogenesis of epilepsy.

PMID- 17506988
TI  - LaRbp38: a Leishmania amazonensis protein that binds nuclear and kinetoplast
      DNAs.
AB  - Leishmania amazonensis causes a wide spectrum of leishmaniasis. There are no
      vaccines or adequate treatment for leishmaniasis, therefore there is considerable
      interest in the identification of new targets for anti-leishmania drugs. The
      central role of telomere-binding proteins in cell maintenance makes these
      proteins potential targets for new drugs. In this work, we used a combination of
      purification chromatographies to screen L. amazonensis proteins for molecules
      capable of binding double-stranded telomeric DNA. This approach resulted in the
      purification of a 38kDa polypeptide that was identified by mass spectrometry as
      Rbp38, a trypanosomatid protein previously shown to stabilize mitochondrial RNA
      and to associate with nuclear and kinetoplast DNAs. Western blotting and
      supershift assays confirmed the identity of the protein as LaRbp38. Competition
      and chromatin immunoprecipitation assays confirmed that LaRbp38 interacted with
      kinetoplast and nuclear DNAs in vivo and suggested that LaRbp38 may have dual
      cellular localization and more than one function.

PMID- 17506989
TI  - Identification of synthetic vaccine candidates against SARS CoV infection.
AB  - Three peptides, D1 (amino acid residues 175-201), D2 (a.a. 434-467), and TM (a.a.
      1128-1159), corresponding to the spike protein (S) of severe acute respiratory
      syndrome corona virus (SARS CoV) were synthesized and their immunological
      functions were investigated in three different animals models (mice, guinea pigs,
      and rabbits). The peptides mixture formulated either with Freund's adjuvant or
      synthetic adjuvant Montanide ISA-51/oligodeoxy nucleotide CpG (ISA/CpG) could
      elicit antisera in immunized animals which were capable of inhibiting SARS/HIV
      pseudovirus entry into HepG2 cells. The neutralizing epitopes were identified
      using peptides to block the neutralizing effect of guinea pig antisera. The major
      neutralizing epitope was located on the D2 peptide, and the amino acid residue
      was fine mapped to 434-453. In BALB/c mice T-cell proliferation assay revealed
      that only D2 peptide contained T-cell epitope, the sequence of which corresponded
      to amino acid residue 434-448. The ISA/CpG formulation generated anti-D2 IgG
      titer comparable to those obtained from Freund's adjuvant formulation, but
      generated fewer antibodies against D1 or TM peptides. The highly immunogenic D2
      peptide contains both neutralizing and Th cell epitopes. These results suggest
      that synthetic peptide D2 would be useful as a component of SARS vaccine
      candidates.

PMID- 17506990
TI  - C. elegans SIN-3 and its associated HDAC corepressor complex act as mediators of
      male sensory ray development.
AB  - Mab21 gene family members are required for embryonic development and sensory
      organ formation in both invertebrates and vertebrates. However, their mechanistic
      role on differentiation is largely unexplored. We report here the isolation of
      SIN-3 as a MAB-21 interacting molecule. sin-3 is co-expressed with mab-21 in the
      ray structural cells and genetically interacts with mab-21 to control sensory
      organ development. Using pharmacological and RNAi approaches, we demonstrated
      that histone deacetylase and conserved SIN-3-associated components are required
      for ray patterning. Conserved physical interactions between these components were
      also observed, implicating the recruitment of HDAC complex by MAB-21/SIN-3 may
      occur to determine ray identity in males.

PMID- 17506991
TI  - Autolysis of a novel multidomain subtilase-cold-adapted deseasin MCP-01 is pH
      dependent and the surface loops in its catalytic domain, the linker, and the
      P_proprotein domain are susceptible to proteolytic attack.
AB  - Cold-adapted deseasin MCP-01 is a novel type subtilase with a multidomain
      structure containing a catalytic domain, a linker, a P_proprotein domain, and a
      PKD domain. Its autolysis was pH-dependent due to its flexible structure. N
      terminal sequence analysis of the autolytic peptides revealed four autolytic
      sites in the catalytic domain. Three of these are in the same loops as mesophilic
      subtilases and one is unlike anything previously reported. Two autolytic sites
      were deduced in its linker and three in its P_proprotein domain, indicating the
      linker and the P_proprotein domain are flexible and susceptible to proteolytic
      attacks. Therefore, during MCP-01 autolysis, the linker and the P_proprotein
      domain of MCP-01 were easily attacked by proteolysis, resulting in cleavage of
      the C-terminal region. At the same time, some autolytic sites in the surface
      loops of the catalytic domain were cleaved. This is the first report describing
      the autolytic mechanism of a multidomain subtilase.

PMID- 17506992
TI  - Modulation of the K(v)4.3 channel by syntaxin 1A.
AB  - The SNARE protein syntaxin 1A (Syn1A) is known to inhibit delayed rectifier K(+)
      channels of the K(v)1 and K(v)2 families with heterogeneous effects on their
      gating properties. In this study, we explored whether Syn1A could directly
      modulate K(v)4.3, a rapidly inactivating K(v) channel with important roles in
      neuroendocrine cells and cardiac myocytes. Immunoprecipitation studies in HEK293
      cells coexpressing Syn1A and K(v)4.3 revealed a direct interaction with increased
      trafficking to the plasma membrane without a change in channel synthesis.
      Paradoxically, Syn1A inhibited K(v)4.3 current density. In particular, Syn1A
      produced a left-shift in steady-state inactivation of K(v)4.3 without affecting
      either voltage dependence of activation or gating kinetics, a pattern distinct
      from other K(v) channels. Combined with our previous reports, our results further
      verify the notion that the mechanisms involved in Syn1A-K(v) interactions vary
      significantly between K(v) channels, thus providing a wide scope for Syn1A
      modulation of exocytosis and membrane excitability.

PMID- 17506993
TI  - Involvement of p38 MAPK in hypotonic stress-induced stimulation of beta- and
      gamma-ENaC expression in renal epithelium.
AB  - We investigated a role of p38 MAPK in the regulation of transepithelial Na(+)
      reabsorption by chronic application (20-24h) of hypotonicity (hypotonic stress)
      in renal epithelial A6 cells. Pretreatment with a specific p38 MAPK inhibitor
      (SB202190) significantly reduced the chronic hypotonicity-stimulated
      transepithelial Na(+) reabsorption by diminishing the Na(+) entry through
      epithelial Na(+) channel (ENaC) in the apical membrane and the Na(+) extrusion
      via the Na(+)/K(+) ATPase (pump), although the rate limiting step was still the
      Na(+) entry step. We further examined whether the inhibitory effects of SB202190
      on the transepithelial Na(+) reabsorption is caused through suppression of mRNA
      expression of ENaC participating in the transepithelial Na(+) reabsorption as the
      Na(+) entry pathway. The chronic hypotonicity increased the mRNA expression of
      alpha-, beta-, and gamma-subunits of ENaC. Moreover, we found that inhibition of
      p38 MAPK by SB202190 diminished the mRNA expression of beta- and gamma-ENaC but
      not alpha-ENaC. Based on these observations, it is suggested that the chronic
      hypotonicity stimulates the renal transepithelial Na(+) reabsorption by
      upregulating the mRNA expression of beta- and gamma-ENaC via a p38 MAPK-dependent
      pathway.

PMID- 17506994
TI  - A transgenic rat expressing human APP with the Swedish Alzheimer's disease
      mutation.
AB  - In recent years, transgenic mice have become valuable tools for studying
      mechanisms of Alzheimer's disease (AD). With the aim of developing an animal
      model better for memory and neurobehavioural testing, we have generated a
      transgenic rat model of AD. These animals express human amyloid precursor protein
      (APP) containing the Swedish AD mutation. The highest level of expression in the
      brain is found in the cortex, hippocampus, and cerebellum. Starting after the age
      of 15 months, the rats show increased tau phosphorylation and extracellular Abeta
      staining. The Abeta is found predominantly in cerebrovascular blood vessels with
      very rare diffuse plaques. We believe that crossing these animals with mutant PS1
      transgenic rats will result in accelerated plaque formation similar to that seen
      in transgenic mice.

PMID- 17506995
TI  - Comparison of 2-aminophenol and 4-nitrophenol as in vitro probe substrates for
      the major human hepatic sulfotransferase, SULT1A1, demonstrates improved
      selectivity with 2-aminophenol.
AB  - Sulfation, catalysed by members of the cytosolic sulfotransferase (SULT) enzyme
      family, is important in xenobiotic detoxification and in the biosynthesis and
      homeostasis of many hormones and neurotransmitters. The major human phenol
      sulfotransferase SULT1A1 plays a key role in chemical defence, is widely
      expressed in the body and is subject to a common polymorphism that results in
      reduced protein levels. Study of these enzymes in vitro requires robust probe
      substrates, and we have previously shown measurement of activity with the widely
      used SULT1A1 substrate, 4-nitrophenol, does not accurately reflect protein
      expression. Additionally, the high degree of substrate inhibition observed with
      this compound further reduces its value as a probe for SULT1A1. Here we show that
      2-aminophenol is a more suitable probe substrate for quantifying SULT1A1 activity
      in human liver. This compound is sulfated at a high rate (V(max) with purified
      recombinant SULT1A1=121nmol/(minmg) and shows strong affinity for the enzyme
      (K(m) with purified recombinant SULT1A1=9microM) and, importantly, is a very poor
      substrate for the other major SULT1 enzyme expressed in liver, SULT1B1 (with
      V(max) and K(m) values of 17nmol/(minmg) and 114microM, respectively).
      Experiments with purified recombinant human SULTs and a panel of 28 human liver
      cytosols demonstrated that 2-aminophenol shows limited substrate inhibition with
      SULT1A1, and V(max) values measured in liver cytosols correlated strongly with
      SULT1A1 enzyme protein levels measured by a quantitative immunoblot method. We
      therefore suggest that 2-aminophenol is a suitable substrate to use for
      quantifying SULT1A1 enzyme activity.

PMID- 17506996
TI  - EndothelinA receptor antagonist BSF-208075 causes immune modulation and
      neuroprotection after stroke in gerbils.
AB  - Leukocytes contribute to the ischemia-reperfusion injury. Recent studies
      suggested endothelins could be important mediators for leukocyte activation in
      stroke. We tested if the endothelinA receptor antagonist BSF-208075 (ambrisentan)
      could reduce an ischemic lesion by modulation of leukocyte-endothelium
      interactions. Twenty-four gerbils underwent either a sham operation (n=6) or 15
      min of bilateral carotid artery occlusion resulting in global cerebral ischemia.
      Ischemic animals received normal saline (n=6), 5 mg/kg BSF-208075 (n=6) or 30
      mg/kg (n=6) administered intravenously at 10 min of reperfusion. Leukocytes
      rolling or adhering to endothelium were counted by intravital microscopy in
      parietal subsurface venules through a closed cranial window. BSF-208075 dose
      dependently reduced postischemic leukocytes rolling (7.3+/-2.3 vs. 3.3+/-1.4 vs.
      0.7+/-0.7 [n/100 microm/min]; p<0.05) and adhering (5.3+/-1.4 vs. 2.7+/-1.6 vs.
      1.3+/-0.5 [n/100 microm/min]; p<0.05). Cerebral blood flow was not significantly
      changed by BSF-208075. Cortical neurons [n/mm2] in an area corresponding to the
      in vivo microscopy were dose-dependently preserved 7 days after ischemia (2456+/
      687 vs. 3254+/-245 vs. 3780+/-168; p<0.05). CONCLUSION: Endothelins mediate
      leukocyte activation in ischemic stroke. The endothelinA receptor antagonist BSF
      208075 administered during reperfusion reduces the postischemic leukocyte
      activation and causes neuroprotection.

PMID- 17506997
TI  - Cognitive control of involuntary attention and distraction in children and
      adolescents.
AB  - The present study focused on the control of involuntary attentional orienting and
      distraction in children (6-8, 10-12 years) and adolescents (17-18 years). In an
      auditory distraction paradigm, pitch deviants interspersed in a sequence of
      standard sounds were presented. In the predictable condition, the type of sound
      (standard or deviant) was announced by a preceding visual cue. In the
      unpredictable condition, the cue was not informative with respect to the type of
      sound. Subjects performed a sound duration discrimination task and were
      instructed to attend the cues in order to avoid distraction. In the unpredictable
      condition, regular behavioral and ERP effects of change detection (Mismatch
      Negativity), attentional orienting (P3a) and distraction (prolonged reaction
      times) were observed. In the predictable condition, no modulation of Mismatch
      Negativity amplitude was observed, whereas the amplitude of P3a and reaction time
      prolongations in deviant trials were reduced in all age groups. Results suggest
      that even young children are able to voluntarily control involuntary attentional
      orienting and behavioral distraction. However, significant age effects were
      observed for the level of behavioral distraction and the selective utilization of
      the visual cues (reflected by P3b).

PMID- 17506998
TI  - Evidence for separate neural mechanisms for the timing of discrete and sustained
      responses.
AB  - Methamphetamine (MAP), an indirect dopamine agonist, has been shown to produce a
      leftward shift in the time of responding under operant response protocols that
      encourage repetitive responding (e.g., lever pressing). Given the involvement of
      striatal dopamine activity in the control of discrete motor behavior, as well as
      in the timing of these responses, an important question arises as to whether a
      dissociation is possible between changes in the timing of discrete responding and
      timing of other behaviors. Rats were trained on a modified peak-interval (PI)
      procedure such that reward was contingent upon the presence of the animal's snout
      in a nosepoke apparatus at the target time, as an alternative to the typical
      requirement of a discrete head entry response. Thus spatial selection, but not
      necessarily motor behavior, at the appropriate time was required to receive a
      reward. Rats were given MAP in one of 3 doses (0.5, 1.0, or 1.5 mg/kg), or a
      saline control injection before PI sessions to determine whether the drug elicits
      a dose-dependent effect on timing of spatial position, as it has been shown to do
      for discrete behaviors. Following administration of MAP, the peak time of the
      proportion of time spent in the nosepoke did not change, while the peak time of
      the rate of response shifted to the left. Single-trial analysis revealed a
      similar pattern: Position of response step functions defined by being in the
      nosepoke did not shift, but step functions based on response rate changed with
      increasing doses of MAP. These data support a model of multiple timing processes
      controlling different behaviors, at least one of which is specific to discrete
      motor behavior and is modifiable by dopamine.

PMID- 17506999
TI  - Experimental charge density of sucrose at 20K: bond topological, atomic, and
      intermolecular quantitative properties.
AB  - The charge density of sucrose was determined from a high-resolution X-ray data
      set measured at 20K. The density distribution so obtained was analyzed
      quantitatively by application of Bader's atoms in molecules (AIM) formalism, and
      a comparison was made with corresponding results from a B3LYP (6-311++G(3df,3pd))
      calculation at the experimental geometry. Bond topological and atomic properties
      (volumes and charges) were derived and compared. The influence of hydrogen
      bonding on the experimental charge density was also studied qualitatively and
      quantitatively by means of topological properties. In terms of the hydrogen-bond
      energies, a grouping into strong, medium and very weak hydrogen bonds was made,
      the latter of which were involved in a bifurcated bond.

PMID- 17507000
TI  - Carbanilation of cereal beta-glucans for molecular weight determination and
      conformational studies.
AB  - Cereal beta-glucans can form aggregates in aqueous solution. The presence of
      aggregates in cereal beta-glucan solutions led to inaccurate determination of
      molecular weights and it was believed that intermolecular hydrogen bonding caused
      the aggregation. To eliminate aggregates, a carbanilation method for molecular
      weight determination of cereal beta-glucans was developed. Wheat beta-glucan
      samples were selected for investigation. The carbanilation method can prevent
      intermolecular hydrogen bonding by blocking hydroxyl groups with phenyl carbamate
      groups. The carbanilates of cereal beta-glucans were prepared by the reaction of
      cereal beta-glucans with phenylisocyanate catalyzed by DMSO and pyridine. To
      avoid degradation during the carbanilation reaction, relatively mild conditions
      were used, which led to incomplete substitution (DS: approximately 2). However,
      after the carbanilation reaction, the carbanilates dissolved completely in 1,4
      dioxane solution without any detectable aggregates, which allowed accurate
      molecular weight determination. The degree of substitution (DS) of carbanilates
      was determined by both a nitrogen content method and an FT-IR method. The FT-IR
      method proved to be the more effective for DS estimation. Using this method, the
      converted molecular weights of cereal beta-glucans were in good agreement with
      the results measured in 0.5M NaOH solution, which previously was shown to be a
      good solvent for cereal beta-glucans. After the carbanilation reaction,
      conformational changes of carbanilates were studied by static and dynamic light
      scattering techniques. The fractal dimension (d(f)=2.27) and the structure
      sensitive parameters (rho >2) suggested a porous globular structure for partially
      carbanilated beta-glucans.

PMID- 17507002
TI  - Distinct involvement of p38-, ERK1/2 and PKC signaling pathways in C5a-mediated
      priming of oxidative burst in phagocytic cells.
AB  - C5a exerts various known harmful functions during experimental sepsis and
      blocking strategies demonstrated survival benefits in experimental sepsis. We
      investigated its potential for priming of oxidative burst in blood neutrophils
      and monocytes and the involvement of various signaling pathways. We here report
      that C5a induced priming of neutrophils and monocytes for Escherichia coli- and
      PMA-induced oxidative burst. This effect was strongly dependent on intact ERK1/2
      signaling. P38 inhibition resulted in abrogation of C5a-induced priming only for
      E. coli-induced oxidative burst and PKC blockade had this effect only for PMA
      induced burst. JNK inhibition had no impact. Our results demonstrate for the
      first time distinct involvement of ERK1/2, p38 and PKC pathways for C5a-induced
      priming of oxidative burst in phagocytes.

PMID- 17507001
TI  - The direct action of 1alpha,25(OH)2-vitamin D3 on purified mouse Langerhans
      cells.
AB  - The action of vitamin D(3) on Langerhans cells (LCs) is not well understood.
      Using highly purified murine LCs (>95%), we investigated the direct action of
      1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on their functions.
      1,25(OH)(2)D(3) inhibited the expression of cell surface molecules including I
      A(d), CD40, CD80, and CD86, leading to impaired ability of LCs to stimulate
      allogenic T cells in the mixed leukocyte reaction. Furthermore, this reagent
      inhibited chemotaxis of LCs to CCL21 and their survival. Interestingly,
      1,25(OH)(2)D(3) reduced the IL-10 production by LCs, whereas the production of IL
      6 and IL-12p40 upon activation by CD40 ligation was enhanced. With regard to
      inflammatory cytokines and chemokines, 1,25(OH)(2)D(3) upregulated the production
      of IL-1beta, CCL3, CCL4, and CCL5. The production of Th2-type chemokines,
      represented by CL17 and CCL22, was inhibited, whereas IFN-gamma-triggered
      production of Th1-type chemokines, represented by CXCL9, CXCL10, and CXCL11, was
      augmented. These data indicate that the mode of regulation of cytokine and
      chemokine production in association with 1,25(OH)(2)D(3) treatment seems to be
      another characteristic discriminating LCs from classical myeloid dendritic cells.

PMID- 17507003
TI  - Alloprenols: novel alpha-trans-polyprenols of Allophylus caudatus.
AB  - A novel type of polyprenols, alloprenols, with an alpha-trans-isoprenoid unit was
      found in the leaves of Allophylus caudatus (Sapindaceae) besides typical alpha
      cis-polyprenols. The polyprenol family (Prenol-11-13, Prenol-12 dominating) was
      accompanied by traces of dolichols of the same chain-length. Prenol alpha-cis-
      and alpha-trans-isomers were chromatographically separated and their structure
      was analyzed by HPLC/ESI-MS, HR-ESI-MS and 1H and 13C NMR spectroscopy. Model
      compounds, semi-synthetic alpha-isomers of all-trans-Pren-9 and mainly-cis-Pren
      11, were obtained using an oxidation-reduction procedure. Comparison of their NMR
      spectra confirmed the structure of the newly identified polyprenols. The observed
      pattern of NMR signal shifts may be applied for elucidation of isoprenoid
      structure.

PMID- 17507004
TI  - Significance of urine protein/creatinine ratio in pregnancy-induced hypertension.

PMID- 17507005
TI  - Persistent NT-proBNP elevation in acute pulmonary embolism predicts early death.
AB  - AIMS: Low levels of brain natriuretic peptides on admission identify low-risk
      patients with acute pulmonary embolism (APE) through their high NPV for
      mortality. However, increased natriuretic peptide values on admission are less
      helpful for identifying high-risk patients due to their low PPV. The aim of the
      study was to test whether the PPV for mortality can be improved by performing
      serial NT-proBNP measurements on admission, at 12 h, and at 24 h. METHODS AND
      RESULTS: We prospectively included 113 consecutive patients with APE (mean age
      63+/-18 years), of whom 10 had clinically massive APE. Thirty-day mortality was
      15% (95% CI: 8%-22%). In survivors, median NT-proBNP levels decreased within 24 h
      from 1895 ng/L (range: 16-33,340) to 1007 ng/L (range: 9-33,243) (p<0.001). In
      non-survivors, median NT-proBNP levels at baseline (11,491 ng/L, range: 618
      60,958) remained elevated at 24 h (8139 ng/L, range: 35-70,018; p=NS). The 30-day
      mortality rate in the group of 18 patients with NT-proBNP >7500 ng/L and less
      than 50% decrease of NT-proBNP within 24 h was 61% (95% CI: 39%-84%). PPV and NPV
      of NT-proBNP >7500 ng/L on admission and less than 50% decrease of NT-proBNP
      within 24 h were 61% and 94%, respectively. CONCLUSION: Persistent elevation of
      plasma NT-proBNP levels within 24 h after APE diagnosis indicates ongoing right
      ventricular dysfunction with a poor prognosis. These critically ill patients may
      be candidates for rapid aggressive intervention, including thrombolysis, catheter
      thrombectomy, or surgical embolectomy.

PMID- 17507006
TI  - Heeding the voice of experience: the role of talker variation in lexical access.
AB  - Two experiments used the head-mounted eye-tracking methodology to examine the
      time course of lexical activation in the face of a non-phonemic cue, talker
      variation. We found that lexical competition was attenuated by consistent talker
      differences between words that would otherwise be lexical competitors. In
      Experiment 1, some English cohort word-pairs were consistently spoken by a single
      talker (male couch, male cows), while other word-pairs were spoken by different
      talkers (male sheep, female sheet). After repeated instances of talker-word
      pairings, words from different-talker pairs showed smaller proportions of
      competitor fixations than words from same-talker pairs. In Experiment 2,
      participants learned to identify black-and-white shapes from novel labels spoken
      by one of two talkers. All of the 16 novel labels were VCVCV word-forms atypical
      of, but not phonologically illegal in, English. Again, a word was consistently
      spoken by one talker, and its cohort or rhyme competitor was consistently spoken
      either by that same talker (same-talker competitor) or the other talker
      (different-talker competitor). Targets with different-talker cohorts received
      greater fixation proportions than targets with same-talker cohorts, while the
      reverse was true for fixations to cohort competitors; there were fewer erroneous
      selections of competitor referents for different-talker competitors than same
      talker competitors. Overall, these results support a view of the lexicon in which
      entries contain extra-phonemic information. Extensions of the artificial lexicon
      paradigm and developmental implications are discussed.

PMID- 17507007
TI  - 1-furan-2-yl-3-pyridin-2-yl-propenone inhibits the invasion and migration of
      HT1080 human fibrosarcoma cells through the inhibition of proMMP-2 activation and
      down regulation of MMP-9 and MT1-MMP.
AB  - Matrix metalloproteinases (MMPs) play important roles in solid tumor invasion and
      migration. In this study, we showed that 1-furan-2-yl-3-pyridin-2-yl-propenone
      (FPP-3) dose-dependently inhibited HT1080 cell invasion and migration, and
      decreased MMP-2 and MMP-9 activities. Furthermore, FPP-3 reduced MMP-2 expression
      at protein and mRNA levels, and suppressed 12-O-tetradecanoylphorbol-13-acetate
      (TPA)-enhanced expression of MT1-MMP without changing tissue inhibitors of
      metalloproteinase (TIMP)-2 level. FPP-3 also suppressed TPA-induced increases in
      MMP-9 protein and mRNA levels, but did not alter TIMP-1 level. Our results
      suggest that FFP-3 may be a valuable anti-invasive drug candidate for cancer
      therapy by suppressing MMP-2, MMP-9, and MT1-MMP.

PMID- 17507008
TI  - Serotonin 5-HT(2C) receptor homodimerization is not regulated by agonist or
      inverse agonist treatment.
AB  - Serotonin 5-HT(2C) receptors represent targets for therapeutics aimed at treating
      anxiety, depression, schizophrenia, and obesity. Previously, we demonstrated that
      5-HT(2C) receptors function as homodimers. Herein, we investigated the effect of
      agonist and inverse agonist treatment on the homodimer status of two naturally
      occurring 5-HT(2C) receptor isoforms, one without basal activity (VGV) and one
      with constitutive activity (INI) with respect to Galpha(q) signaling. Cyan- and
      yellow-fluorescent proteins were used to monitor VGV and INI homodimer formation
      by western blot, and in living cells using bioluminescence and fluorescence
      resonance energy transfer (BRET and FRET). Western blots of solubilized membrane
      proteins revealed equal proportions of homodimeric receptor species from HEK293
      cells transfected with either the VGV or INI isoform in the absence and presence
      of 5-HT. BRET ratios measured in HEK293 cells transfected with the VGV or INI
      isoform were the same and were not modulated by 5-HT. Similarly, FRET
      efficiencies were the same regardless of whether measured in cells expressing the
      VGV or INI isoform in the absence or presence of 5-HT or clozapine. The results
      indicate that serotonin 5-HT(2C) receptors form homodimers regardless of whether
      they are in an inactive or active conformation and are not regulated by drug
      treatment.

PMID- 17507009
TI  - Clonorchis sinensis: expression, characterization, immunolocalization and
      serological reactivity of one excretory/secretory antigen-LPAP homologue.
AB  - From a Clonorchis sinensis adult cDNA plasmid library, a cDNA clone encoding a
      novel lysophosphatidic acid phosphatase (LPAP) homologue was isolated. The
      predicted molecular weight of putative protein was 48.8 kDa and the deduced amino
      acid sequence had 45%, 32%, and 29% identity with LPAP of Schistosoma japonicum,
      Danio rerio, and Homo sapiens, respectively. Prediction of signal peptide and
      Western blot analysis indicated that the CsLPAP homologue was an excretory
      secretory antigen (ES antigen) of C. sinensis. Immunostaining revealed that the
      CsLPAP was markedly localized in the intestinal cecum, seminal receptacle and
      eggs of the adult worm. The recombinant CsLPAP showed slightly higher sensitivity
      (82.14%) and specificity (85.86%) than the crude worm antigen by enzyme-linked
      immunosorbent assay (ELISA), a result which suggested that the recombinant
      antigen might be valuable in the serodiagnosis of human clonorchiasis.

PMID- 17507010
TI  - Requirements for a conservative protein translocation pathway in chloroplasts.
AB  - The chloroplast inner envelope translocon subunit Tic110 is imported via a
      soluble stromal translocation intermediate. In this study an in-organellar import
      system is established which allows for an accumulation of this intermediate in
      order to analyze its requirements for reexport. All results demonstrate that the
      re-export of Tic110 from the soluble intermediate stage into the inner envelope
      requires ATP hydrolysis, which cannot be replaced by other NTPs. Furthermore, the
      molecular chaperone Hsp93 seems prominently involved in the reexport pathway of
      Tic110, because other stromal intermediates like that of the oxygen evolving
      complex subunit OE33 (iOE33) en route to the thylakoid lumen interacts
      preferentially with Hsp70.

PMID- 17507011
TI  - Human immortalized chondrocytes carrying heterozygous FGFR3 mutations: an in
      vitro model to study chondrodysplasias.
AB  - Achondroplasia and thanatophoric dysplasia are human chondrodysplasias caused by
      mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We have
      developed an immortalized human chondrocyte culture model to study the regulation
      of chondrocyte functions. One control and eight mutant chondrocytic lines
      expressing different FGFR3 heterozygous mutations were obtained. FGFR3 signaling
      pathways were modified in the mutant lines as revealed by the constitutive
      activation of the STAT pathway and an increased level of P21(WAF1/CIP1) protein.
      This model will be useful for the study of FGFR3 function in cartilage studies
      and future therapeutic approaches in chondrodysplasias.

PMID- 17507012
TI  - From affiliative behaviors to romantic feelings: a role of nanopeptides.
AB  - Love is one of the most desired experiences. The quest for understanding human
      bonds, especially love, was traditionally a domain of the humanities. Recent
      developments in biological sciences yield new insights into the mechanisms
      underlying the formation and maintenance of human relationships. Animal models of
      reproductive behaviors, mother-infant attachment and pair bonding complemented by
      human studies reveal neuroendocrine foundations of prosocial behaviors and
      emotions. Amongst various identified neurotransmitters and modulators, which
      control affiliative behaviors, the particular role of nanopeptides has been
      indicated. New studies suggest that these chemicals are not only involved in
      regulating bonding processes in animals but also contribute to generating
      positive social attitudes and feelings in humans.

PMID- 17507013
TI  - Cell stress induced HSP are targets of regulatory T cells: a role for HSP
      inducing compounds as anti-inflammatory immuno-modulators?
AB  - T cell responses to heat shock proteins (HSP) have disease suppressive activities
      through production of anti-inflammatory cytokines in patients and in models of
      inflammatory diseases. There is evidence that the anti-inflammatory activity of
      HSP-specific T cells depends on their recognition of endogenous HSP epitopes as
      expressed by stressed cells at sites of inflammation. Previously, we have
      demonstrated that such T cells can be induced by conserved sequences of microbial
      HSP. Now we propose that drug induced up-regulation of endogenous HSP can
      contribute to anti-inflammatory T cell regulation.

PMID- 17507014
TI  - Homologous desensitization and visualization of the tilapia GnRH type 3 receptor.
AB  - Two types of gonadotropin-releasing hormone (GnRH) receptors were found in the
      pituitary of tilapia (t), named GnRHR type 3 (tGnRHR3) and GnRHR type 1,
      according to phylogenetic analysis. tGnRHR3 is highly expressed in the posterior
      part of the pituitary which contains LH and FSH cells. We characterized tGnRHR3
      in terms of both LH release rate and receptor internalization rate in response to
      continuous exposure to GnRH. Constant exposure of tilapia pituitary fragments to
      salmon GnRH analog (sGnRHa) resulted in an increased secretion rate for 3h,
      followed by a gradual decline, taking 17-19h, to the basal secretion rate. A
      chimera between tGnRHR3 and green fluorescent protein (GFP) was created and used
      to observe the changes in receptor distribution and translocation, activated by
      agonist with time. The results suggested that the receptor is initially localized
      at the plasma membrane and upon activation by a homologous ligand (e.g. sGnRHa)
      undergoes relatively rapid endocytosis. In summary, the present work demonstrates
      that tGnRHR3 has already undergone endocytosis after 30min, while desensitization
      of LH release occurs only after 17-19h. It is concluded that for tGnRHR3,
      internalization of the receptor is not exclusively responsible for the
      desensitization of LH release.

PMID- 17507016
TI  - Development of specific enzyme-linked immunosorbent assay for determining LH and
      FSH levels in tilapia, using recombinant gonadotropins.
AB  - We recently produced Oreochromis niloticus recombinant LH and FSH as single-chain
      polypeptides in the methylotrophic yeast Pichia pastoris. Glycoprotein subunit
      alpha was joined with tilapia (t) LHbeta or tFSHbeta mature protein-coding
      sequences to form a fusion gene that encodes a ;;tethered" polypeptide, in which
      the gonadotropin beta-subunit forms the N-terminal part and the alpha-subunit
      forms the C-terminal part. Recombinant (r) gonadotropins were used to develop
      specific and homologous competitive ELISAs for measurements of FSH and LH in the
      plasma and pituitary of tilapia, using primary antibodies against rtLHbeta or
      rtFSHbeta, respectively, and rtLHbetaalpha or rtFSHbetaalpha for the standard
      curves. The wells were coated with either rtLHbeta (2ng/ml) or rtFSHbeta
      (0.5ng/well), and the final concentrations of the antisera were 1:5000 (for tLH)
      or 1:50,000 (for tFSH). The sensitivity of the assay was 15.84pg/ml for tLH and
      0.24pg/ml for tFSH measurements in the plasma, whereas for the measurements in
      the pituitary, the sensitivity was 2.43ng/ml and 1.52ng/ml for tLH and tFSH,
      respectively. The standard curves for tFSH and tLH paralleled those of serially
      diluted pituitary extracts of other cichlids, as well as of serially diluted
      pituitary extract of seabream, European seabass and hybrid bass. We examined
      plasma tFSH and tLH levels in the course of one reproductive cycle, between two
      successive spawnings, in three individual tilapia females. Plasma levels of both
      FSH and LH increased during the second day after the eggs had been removed,
      probably related to the vitellogenic phase. LH levels increased toward spawning,
      which occurred on the 11th day. FSH levels also increased on day of cycle,
      probably due to recruitment of a new generation of follicles for the successive
      spawning. The development of specific ELISAs using recombinant gonadotropins is
      expected to advance the study of the distinct functions of each of these
      important hormones.

PMID- 17507015
TI  - Complex steroid-peptide-receptor cascade controls insect ecdysis.
AB  - Insect ecdysis sequence is composed of pre-ecdysis, ecdysis and post-ecdysis
      behaviors controlled by a complex cascade of peptide hormones from endocrine Inka
      cells and neuropeptides in the central nervous system (CNS). Inka cells produce
      pre-ecdysis and ecdysis triggering hormones (ETH) which activate the ecdysis
      sequence through receptor-mediated actions on specific neurons in the CNS.
      Multiple experimental approaches have been used to determine mechanisms of ETH
      expression and release from Inka cells and its action on the CNS of moths and
      flies. During the preparatory phase 1-2 days prior to ecdysis, high ecdysteroid
      levels induce expression of ETH receptors in the CNS and increased ETH production
      in Inka cells, which coincides with expression of nuclear ecdysone receptor (EcR)
      and transcription factor cryptocephal (CRC). However, high ecdysteroid levels
      prevent ETH release from Inka cells. Acquisition of Inka cell competence to
      release ETH requires decline of ecdysteroid levels and beta-FTZ-F1 expression few
      hours prior to ecdysis. The behavioral phase is initiated by ETH secretion into
      the hemolymph, which is controlled by two brain neuropeptides-corazonin and
      eclosion hormone (EH). Corazonin acts on its receptor in Inka cells to elicit low
      level ETH secretion and initiation of pre-ecdysis, while EH induces cGMP-mediated
      ETH depletion and consequent activation of ecdysis. The activation of both
      behaviors is accomplished by ETH action on central neurons expressing ETH
      receptors A and B (ETHR-A and B). These neurons produce numerous excitatory or
      inhibitory neuropeptides which initiate or terminate different phases of the
      ecdysis sequence. Our data indicate that insect ecdysis is a very complex process
      characterized by two principal steps: (1) ecdysteroid-induced expression of
      receptors and transcription factors in the CNS and Inka cells. (2) Release and
      interaction of Inka cell peptide hormones and multiple central neuropeptides to
      control consecutive phases of the ecdysis sequence.

PMID- 17507017
TI  - On the optimization of a rolling-force model for a hot strip finishing line.
AB  - This paper starts with a profound analysis of rolling-force calculation models of
      two hot strip rolling product lines. According to classical theory of rolling
      force calculation, the structure of rolling-force calculation model is firstly
      optimized. Then with application of data mining techniques, including clustering
      sampling approach and optimization algorithm, to the field data from product
      line, the value of key coefficients of the model is adjusted. By the proposed
      optimization scheme, a better rolling-force prediction is achieved.

PMID- 17507018
TI  - Optimal load distribution between units in a power plant.
AB  - This paper presents a strategy for load distribution between the generating units
      in hydro power plants. The objective is to reach the maximum energy conversion
      efficiency for a given dispatched power. The developed tool employs a heuristic
      based combinatorial optimization technique in conjunction with a set of system
      variables measurement allowing real-time load sharing. The developed equipment is
      used to give online energy conversion efficiency from each unit of the power
      plant. No specific previous information about the efficiency of system components
      is required. Simulation results of the proposed optimization technique when
      applied to typical hydro power plant data are presented.

PMID- 17507019
TI  - The 434(G>C) polymorphism within the coding sequence of Eosinophil Cationic
      Protein (ECP) correlates with the natural course of Schistosoma mansoni
      infection.
AB  - Schistosomiasis is a chronic parasitic infection with over 200 million people
      infected worldwide. In Schistosoma mansoni infections, parasite-derived eggs get
      trapped in the liver, causing the formation of granulomas, which may develop into
      periportal fibrosis and portal hypertension, and thus severe morbidity.
      Eosinophil cationic protein (ECP) is a secretory protein of eosinophil
      granulocytes that efficiently kills the larval stage of S. mansoni, but also
      affects fibroblast functions. We have investigated the prevalence of the ECP gene
      polymorphism 434(G>C) in two African populations, from an S. mansoni endemic area
      in Uganda (n=297) and from a non-endemic area in Sudan (n=78), and also compared
      these with a Swedish population (n=209). The genotype frequencies in the Ugandan
      population differed significantly from both the Sudanese and Swedish populations
      (P<0.001). In the Ugandan population there was a significant association between
      genotype and prevalence of infection (P=0.03), with lower prevalence in subjects
      with the GG genotype compared with GC (P=0.02) and CC (P=0.03). There was also a
      trend towards an association with periportal fibrosis (P=0.08) in the Ugandan
      population. This suggested association was confirmed when the predominant tribe
      (n=212) was analysed separately (P=0.004). Our results suggest that ECP may be an
      important protein, both in the immune response against S. mansoni and in the
      development of periportal fibrosis. The results also suggest genetic selection
      towards the ECP 434CC genotype in populations living in S. mansoni endemic areas.

PMID- 17507020
TI  - Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events.
AB  - BACKGROUND: Tissue proportions of long chain n-6 [especially arachidonic acid
      (AA)] and n-3 fatty acids [FA; eicosapentaenoic acid (EPA) and docosahexaenoic
      acid (DHA) acids], or some ratio of these may be markers of risk for coronary
      heart disease (CHD). The purpose of this paper is to evaluate the published
      associations between risk for CHD events and tissue n-3 and n-6 FA composition.
      METHODS: Case-control or prospective cohort data sets examining the risk for CHD
      endpoints as a function of tissue FA composition were identified. Effect sizes
      were computed for case versus control comparisons using standard meta-analytic
      methods. RESULTS: Twenty-five studies were included, 18 examining the FA
      composition of phospholipid-rich and 7 of triglyceride-rich samples. DHA, with or
      without EPA, was significantly lower in cases than controls in all studies
      combined, in those with fatal endpoints, in those with prospective designs, and
      in both tissue types. The only setting where increased AA was associated with
      case status was in adipose tissue. The AA/EPA ratio in phospholipid-rich samples
      did not distinguish cases from controls. Lower linoleic acid content was
      associated with increased risk for non-fatal events. CONCLUSIONS: The long-chain
      n-3 FA, especially DHA, were consistently and significantly reduced in patients
      experiencing CHD events. These findings add further support to the view that long
      chain n-3 FA are cardioprotective.

PMID- 17507021
TI  - A three-dimensional model of fluid-structural interactions for quantifying the
      contractile force for cardiomyocytes on hybrid biopolymer microcantilever.
AB  - Quantitatively analysis of the contractility of cardiomyocytes is important for
      understanding the mechanism of heart failure as well as the molecular alterations
      in diseased heart cells. This paper presents a realistic computational model,
      which considers the three-dimensional fluid-structural interactions (FSI), to
      quantify the contractile force of cardiomyocytes on hybrid biopolymer
      microcantilevers. Prior to this study, only static modeling of the microscale
      cellular force has been reported. This study modeled the dynamics of
      cardiomyocytes on microcantilevers in a medium using the FSI. This realistic
      model was compared with static finite element modeling (FEM) analysis and the
      Stoney's equation-based analytical solution, and was validated by the deflections
      of the microcantilevers in the experimental results. Using harmonic response
      analysis in FSI modeling, the motion of a hybrid biopolymer microcantilever in
      the medium was identified as a second-order system and the influence of the
      dynamics of cardiomyocytes could be evaluated quantitatively.

PMID- 17507022
TI  - Development of the chromatographic partitioning of cesium and strontium utilizing
      two macroporous silica-based calix[4]arene-crown and amide impregnated polymeric
      composites: PREC partitioning process.
AB  - To partition effectively Cs(I) and Sr(II), two harmful heat emitting nuclides,
      from a highly active liquid waste by extraction chromatography, two kinds of
      macroporous silica-based polymeric materials, Calix[4]arene-R14/SiO(2)-P and
      TODGA/SiO(2)-P, were synthesized. Two chelating agents, 1,3-[(2,4-diethyl
      heptylethoxy)oxy]-2,4-crown-6-calix[4]arene (Calix[4]arene-R14), an excellent
      supramolecular compound having molecular recognition ability for Cs(I), and
      N,N,N',N'-tetraoctyl-3-oxapentane-1,5-diamide (TODGA) were impregnated and
      immobilized into the pores of SiO(2)-P particles support by a vacuum sucking
      technique. The loading and elution of 11 typical simulated fission and non
      fission products from 4.0M or 2.0M HNO(3) were performed at 298K. It was found
      that in the first column packed with the Calix[4]arene-R14/SiO(2)-P, all of the
      simulated elements were separated effectively into two groups: (1) Na(I), K(I),
      Sr(II), Fe(III), Ba(II), Ru(III), Pd(II), Zr(IV), and Mo(VI) (noted as Sr-group);
      (2) Cs(I)-Rb(I) (Cs-group) by eluting with 4.0M HNO(3) and distilled water,
      respectively. The harmful element Cs(I) flowed into the second group along with
      Rb(I) because of their close sorption and elution properties towards
      Calix[4]arene-R14/SiO(2)-P, while Sr(II) showed no sorption and flowed into Sr
      containing group. In the second column packed with TODGA/SiO(2)-P, the Sr-group
      was separated into (1) Ba(II), Ru(III), Na(I), K(I), Fe(III), and Mo(VI) (non
      sorption group); (2) Sr(II); (3) Pd(II); and (4) Zr(IV) by eluting with 2.0M
      HNO(3), 0.01M HNO(3), 0.05M DTPA-pH 2.5, and 0.5M H(2)C(2)O(4), respectively.
      Sr(II) adsorbed towards TODGA/SiO(2)-P flowed into the second group and showed
      the excellent separation efficiency from others. Based on the elution behavior of
      the tested elements, an advanced PREC (Partitioning and Recovery of two heat
      generators from an acidic HLW (high activity liquid waste) by Extraction
      Chromatography) process was proposed.

PMID- 17507023
TI  - Matrix effect in liquid chromatography-electrospray ionization mass spectrometry
      analysis of benzoxazinoid derivatives in plant material.
AB  - Despite the increasing success of liquid chromatography (LC) coupled to mass
      spectrometry (MS), matrix effects have limited the ESI applications. Matrix
      effects result from co-eluting residual matrix components affecting the
      ionization efficiency of target analytes and can lead to erroneous results. The
      present work evaluates the LC-electrospray ionization (ESI)-MS behaviour of
      benzoxazinoid derivatives in wheat plant material as a case where endogenous
      matrix components were found to interfere with the ionization of target analytes.
      When LC-MS was applied to the analysis of foliage and root extracts, significant
      signal suppressions were observed. To compensate for this matrix signal
      suppression, different methods were applied: the use of internal standards, the
      application of standard dilution method and the dilution of the extracts before
      instrumental determination. The results obtained indicated that evaluation of
      matrix effects should become an integrated part of quantitative LC-ESI-MS method
      development and validation.

PMID- 17507024
TI  - Characterization of procaine metabolism as probe for the butyrylcholinesterase
      enzyme investigation by simultaneous determination of procaine and its metabolite
      using capillary electrophoresis with electrochemiluminescence detection.
AB  - Capillary electrophoresis with electrochemiluminescene detection was used to
      characterize procaine hydrolysis as a probe for butyrylcholinesterase by in vitro
      procaine metabolism in plasma with butyrylcholinesterase acting as bioscavenger.
      Procaine and its metabolite N,N-diethylethanolamine were separated at 16 kV and
      then detected at 1.25 V in the presence of 5.0 mM Ru(bpy)(3)2+, with the
      detection limits of 2.4x10(-7) and 2.0x10(-8) mol/L (S/N=3), respectively. The
      Michaelis constant Km value was 1.73x10(-4) mol/L and the maximum velocity Vmax
      was 1.62x10(-6) mol/L/min. Acetylcholine bromide and choline chloride presented
      inhibition effects on the enzymatic cleavage of procaine, with the 50% inhibition
      concentration (IC50) of 6.24x10(-3) and 2.94x10(-4) mol/L.

PMID- 17507025
TI  - Gas chromatographic-mass spectrometric determination of alkylphosphonic acids
      from aqueous samples by ion-pair solid-phase extraction on activated charcoal and
      methylation.
AB  - In the present paper, we report an improved ion-pair solid-phase extraction (IP
      SPE) method for the analysis of alkylphosphonic acids, namely, methyl, ethyl and
      propylphosphonic acids, present in the aqueous sample. The aqueous sample was
      mixed with an ion-pair reagent, phenyltrimethylammonium hydroxide (PTMAH) and
      passed through activated charcoal SPE cartridge. The retained chemicals in the
      cartridge were extracted with methanol and analysed by gas chromatography-mass
      spectrometry (GC-MS) under the electron impact ionization (EI) mode. The analytes
      were converted to their methyl esters by pyrolytic methylation in the hot GC
      injection port. The recoveries of alkylphosphonic acids were above 95% and the
      minimum detection limits were as low as 10 ng/mL. The recovery of the test
      chemicals was tested with solvents, dichloromethane, n-hexane, ethyl acetate,
      acetone, acetonitrile and methanol. The chemicals could be efficiently extracted
      by the hydrophilic solvents. The method did not work at the highly acidic pH
      (when acidified with dilute HCl) but worked well from pH 4.0 to 14.0. The present
      method was also tested with other tetra-(methyl, ethyl, propyl and n
      butyl)ammonium hydroxides. The test chemicals were not converted to their methyl
      and ethyl esters with tetramethyl and tetraethylammonium hydroxides, whereas they
      were converted to their corresponding propyl and n-butyl esters with tetrapropyl
      and tetra(n-butyl)ammonium hydroxides. The method was also applied to two highly
      cross-linked polymeric sorbents DSC-6S and Oasis HLB. The recovery of the
      chemicals on these sorbents was observed to be poor. Methylation using
      phenyltrimethylammonium hydroxide is non-hazardous and advantageous over
      methylation using diazomethane. The method was applied to the analysis of aqueous
      samples given in one of the official proficiency tests conducted by the
      Organization for the Prohibition of Chemical Weapons and all the spiked chemicals
      were identified as methyl esters.

PMID- 17507026
TI  - Equilibrium and kinetic analysis of CO2-N2 adsorption separation by concentration
      pulse chromatography.
AB  - CO2 and N(2) adsorption kinetics and equilibrium behaviours have been studied
      with silicalite, NaY and 13X by using concentration pulse chromatography for the
      separation of these gases in the present study. Adsorption Henry's Law constants,
      the heat of adsorption values, micropore diffusion coefficients and corresponding
      activation energies are determined experimentally and the three different mass
      transfer mechanisms are discussed. From the equilibrium data, the corresponding
      separation factors are obtained for the adsorption separation processes. The heat
      of adsorption values as well as the Henry's Law adsorption equilibrium constants
      of CO(2) are much higher than those of N(2) for all the adsorbents studied. 13X,
      NaY and silicalite all have good separation factors for CO(2)/N(2) system based
      on equilibrium processes. The order of the equilibrium separation factors is 13X
      (Ceca)>13X (Zeochem)>NaY (UOP)>>silicalite (UOP). Equilibrium selectivity favours
      CO(2) over N(2). Micropore diffusion resistance is the definite dominant mass
      transfer mechanism for CO(2) with silicalite and NaY.

PMID- 17507027
TI  - Study on reaction kinetics of synthesis of thioether by a visualization
      technique.
AB  - In this paper, a novel technique combined light-electronic microscopy and
      computer imaging trace was used to investigate the synthesis of thioether, which
      is an intermediate for lansoprazole. The reaction kinetics study by a
      visualization technique was carried out in a minireactor, and the concentration
      grayscale standard curves for thioether were obtained by analyzing the grayscales
      of digital images for the solutions with 20 different concentrations. Based on
      the concentration-grayscale standard curves, the reactant concentrations at
      different times were calculated and the reaction kinetic curve as well as the
      reaction rate equation were obtained. It was found that the total mass-transfer
      resistance of sodium imidazole was larger than that of bromopyridine. Liquid
      liquid interface of synthesizing thioether was observed and its mass transfer
      mechanism was discussed.

PMID- 17507028
TI  - Structural and functional characterization of enantiomeric glutamic acid
      derivatives as potential transition state analogue inhibitors of MurD ligase.
AB  - Mur ligases play an essential role in the intracellular biosynthesis of bacterial
      peptidoglycan, the main component of the bacterial cell wall, and represent
      attractive targets for the design of novel antibacterials. UDP-N-acetylmuramoyl-L
      alanine:D-glutamate ligase (MurD) catalyses the addition of D-glutamic acid to
      the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA) and is the
      second in the series of Mur ligases. MurD ligase is highly stereospecific for its
      substrate, D-glutamic acid (D-Glu). Here, we report the high resolution crystal
      structures of MurD in complexes with two novel inhibitors designed to mimic the
      transition state of the reaction, which contain either the D-Glu or the L-Glu
      moiety. The binding modes of N-sulfonyl-D-Glu and N-sulfonyl-L-Glu derivatives
      were also characterised kinetically. The results of this study represent an
      excellent starting point for further development of novel inhibitors of this
      enzyme.

PMID- 17507029
TI  - A presenilin 1 mutation (Arg278Ser) associated with early onset Alzheimer's
      disease and spastic paraparesis.
AB  - Early onset familial Alzheimer's disease (EOFAD) has been associated with
      mutations in three genes, of which presenilin 1 (PSEN1) mutations are the most
      frequent. Several families with an association of progressive dementia and
      spastic paraplegia caused by PSEN1 mutations have been described. Here we
      described a novel PSEN1 mutation that was associated with dementia and spastic
      paraplegia in a family with 5 affected individuals in three generations. The
      proband was a 44-year-old woman who presented with 5 years history of progressive
      difficulties in walking, cognition and visuospatial impairment. Her maternal
      grandmother, mother and two maternal aunts also had similar neurological
      presentation. Molecular genetic analysis showed a missense mutation predicted to
      substitute an arginine residue for a serine residue at position 278 in the PSEN1
      polypeptide (Arg278Ser). The novel PSEN1 mutation identified in this patient adds
      to the diverse list of existing mutations causing EOFAD associated with spastic
      paraparesis.

PMID- 17507030
TI  - Ideomotor apraxia: a review.
AB  - Ideomotor apraxia (IMA) is a disorder traditionally characterized by deficits in
      properly performing tool-use pantomimes (e.g., pretending to use a hammer) and
      communicative gestures (e.g., waving goodbye). These deficits are typically
      identified with movements made to verbal command or imitation. Questions about
      this disorder relate to its diagnosis, anatomical correlates, physiological
      mechanisms involved, and the patients in whom IMA is best characterized. In this
      review, utilizing information presented at an international workshop, we
      summarize the present state of knowledge about IMA. We include insights on how to
      distinguish IMA from the other motor apraxias and confounding disorders. We
      discuss testing for IMA and the need for more rigorous tests that examine more
      elements, such as imitation, actual use, task selection, and recognizing proper
      use. From neurophysiological insights, we propose hypotheses of the necessity of
      networks in praxis performance. We also point out that more neurophysiological
      knowledge in humans might lead to a better understanding of how different brain
      structures may aid in the rehabilitation of praxis. While little is known about
      exactly how rehabilitation may be pursued, biological evidence warrants the
      further exploration of this issue.

PMID- 17507031
TI  - Combination therapy in multiple sclerosis.
AB  - Multiple sclerosis is an inflammatory/demyelinating and neurodegenerative
      disease. Treatment of MS is currently based on various different therapeutic
      algorithms of a sequential or escalating therapy with immunomodulators or
      immunosuppressants, generated partly from evidence based medicine and partly from
      expert's consensus. However, these therapies are not always effective as
      monotherapies. An alternative would be the combination of agents which already
      have some proven efficacy in MS therapy, are directed against different
      mechanisms of the pathogenic chain, and ideally result in synergic effects and a
      profile of reduced toxicity. Combination therapy in multiple sclerosis can be:
      Combination of two or more anti-inflammatory agents or combination of anti
      inflammatory agents plus neuroprotective agents. Many combinations of drugs have
      been or are being tested in multiple sclerosis. Clinical trials have included a
      low number of patients for short periods of time. Preliminary studies on safety
      suggest that some combination therapies might be safe and efficacious. Ongoing
      and new phase III clinical trials involving a greater number of patients for
      longer periods of time are needed to verify this hypothesis. A wise balance
      between efficacy and safety and extremely clear information to patients should
      drive clinical decisions.

PMID- 17507032
TI  - Sampling species abundance distributions: resolving the veil-line debate.
AB  - Preston's classic work on the theory of species abundance distributions (SADs) in
      ecology has been challenged by Dewdney. Dewdney contends that Preston's veil-line
      concept, relating to the shape of sample SADs, is flawed. Here, I show that
      Preston's and Dewdney's theories can be reconciled by considering the differing
      mathematical properties of the sampling process on logarithmic (Preston) versus
      linear (Dewdney) abundance scales. I also derive several related results and
      show, importantly, that one cannot reject the log-normal distribution as a
      plausible SAD based only on sampling arguments, as Dewdney and others have done.

PMID- 17507033
TI  - Does a tag system effectively support emerging cooperation?
AB  - This paper investigates whether the so-called Tag Systems support emerging
      cooperation with respect to 2x2 games. The Tag System, initially proposed by
      Riolo et al. [2001. Evolution of cooperation without reciprocity. Nature 414, 441
      443], gives each agent both a Tag and Tol defined by [0,1] real numbers. Tol is a
      tolerance for recognizing an opponent as a company. Both Tag and Tol are assumed
      to be evolving. Results show that the tag's effectiveness depends on whether the
      AllD strategy is allowed in the system. Allowing AllD implies that green beard
      effect does not work in the system. Thus, (1) the tag's effectiveness is more
      meager than that reported by Riolo et al., (2) the Tag System can use alternating
      reciprocity more effectively than the analytic solution in a Hero game; (3) a
      system using a 2D tag space supports cooperation more effectively than the usual
      Tag System.

PMID- 17507034
TI  - Effect of feedback regulation on stochastic gene expression.
AB  - Stochastic noise in gene expression arises as a result of species in small copy
      number undergoing transitions between discrete chemical states. Here the noise in
      a single gene network is investigated using the Omega-expansion techniques. We
      show that the linear noise approximation implies an invariant relationship
      between the normalized variances and normalized covariance in steady-state
      statistics. This invariant relationship provides an exactly statistical
      interpretation for why the stochastic noise in gene expression should be measured
      by the normalized variance. The nature of the normalized variance reveals the
      basic relationship between the stochasticity and system size in gene expression.
      The linear noise approximation implies also that for both mRNA and protein, the
      total noise can be decomposed into two basic components, one concerns the
      contribution of average number of molecules, and other the contribution of
      interactions between mRNA and protein. For the situation with linear feedback,
      our results clearly show that for two genes with the same average number of
      protein molecules, the gene with negative feedback will have a small protein
      noise, i.e., the negative feedback will reduce the protein noise. For the effect
      of the burst size on the protein noise, we show also that the protein intrinsic
      noise will decrease with the increase of the burst size, but the protein
      extrinsic noise is independent of the burst size.

PMID- 17507035
TI  - Re: circumcision--are you with us or against us? J. S. Elder J Urol 2006; 176:
      1911.

PMID- 17507036
TI  - Re: choices. M. I. Resnick J Urol 2006; 176: 2342.

PMID- 17507037
TI  - Voiding function and dysfunction, bladder physiology and pharmacology, and female
      urology. A. J. Wein J Urol 2007; 177: 230-233.

PMID- 17507038
TI  - Re: can restaging transurethral resection of T1 bladder cancer select patients
      for immediate cystectomy? H. W. Herr, S. M. Donat and G. Dalbagni J Urol 2007;
      177: 75-79.

PMID- 17507039
TI  - Re: expression of major heat shock proteins in prostate cancer: correlation with
      clinicopathological outcomes in patients undergoing radical prostatectomy. T.
      Kurahashi, H. Miyake, I. Hara and M. Fujisawa J Urol 2007; 177: 757-761.

PMID- 17507040
TI  - Infertility and hypergonadotropic hypogonadism as first evidence of hereditary
      apolipoprotein A-I amyloidosis.
AB  - PURPOSE: We report that primary infertility and hypergonadotropic hypogonadism in
      young patients may be caused by testicular amyloidosis and it is associated with
      the presence of a mutation in the apoA-I gene, resulting in the replacement of
      proline for leucine at residue 75 of the protein. MATERIALS AND METHODS: Ten
      patients presenting with infertility, gynecomastia, decreased libido, erectile
      dysfunction or a family history of amyloidosis underwent clinical evaluation,
      hormone assays, semen analysis, ultrasonographic investigation of the testicles,
      testicular biopsy and DNA sequencing of the apoA-I gene. RESULTS: All patients
      showed azoospermia and 9 had increased testicular volume. Massive amyloid
      deposition was observed in all testicular biopsies and the apoA-I mutation of
      replacement of proline for leucine at residue 75 of the protein was noted. Five
      patients showed hypergonadotropic hypogonadism and 5 had normal testosterone
      values with high gonadotropin levels. CONCLUSIONS: Nonobstructive azoospermia and
      macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I
      amyloidosis in young patients. Testicular amyloidosis can be the first
      manifestation of this systemic disease. Specific staining for amyloid deposits
      and genetic analysis of apoA-I mutations are recommended in young, infertile
      patients with macro-orchidism. Finally, surveillance in asymptomatic mutation
      carriers is suggested to evaluate the opportunity to implement sperm retrieval
      and start androgen replacement therapy when necessary.

PMID- 17507041
TI  - Intraurethral transfer of satellite cells by myofiber implants results in the
      formation of innervated myotubes exerting tonic contractions.
AB  - PURPOSE: We investigated a new method of muscle precursor cell transfer in the
      urethra for the treatment of urinary incontinence, consisting of implanting
      myofibers with their satellite cells. MATERIALS AND METHODS: In preliminary
      experiments to test the regenerative capacities of satellite cells histological
      analysis was performed on days 7 and 30 after the implantation of myofiber cores
      in the urethra of 6 female pigs. In the main experiments 11 pigs underwent
      baseline urodynamics, followed by endoscopic destruction of the striated urethral
      sphincter located around the distal urethra (day 0). On day 30 circular myofiber
      strips in 7 experimental cases and adipocytes in 4 controls were implanted in the
      proximal urethra. Seven days later (day 37) 1 case was sacrificed to verify
      satellite cell activation. On day 60 urodynamics were performed without and with
      curarization. Urethral cryosections were immunostained for desmin (activated
      satellite cells), fast myosin heavy chain/bungarotoxin (myotubes/acetylcholine
      receptors), neurofilament/vesicular acetylcholine transporter (nerve endings) and
      CD45/CD68 (inflammatory response). RESULTS: Preliminary histological studies
      revealed a myogenic process consisting of myofiber degeneration and satellite
      cell activation (day 7), followed by myotube formation replacing parental
      myofibers (day 30). In the main experiments endoscopic injury abolished striated
      urethral sphincter activity. Implantation of myofiber strips generated a pressure
      peak that decreased after curarization (mean+/-SEM 71.5+/-17.8 vs 33.5+/-14.8 cm
      H2O, p=0.031) and reappeared 60 minutes later, revealing that this action was
      tonic and under neural control. Nerve endings connected to the acetylcholine
      receptors of myotubes were observed on day 60. An inflammatory response was
      observed only on day 7 in the myofiber implantation group. Adipocyte implantation
      resulted in no significant intraurethral pressure changes. CONCLUSIONS: Urethral
      implantation of myofibers regenerates as myotubes that exert tonic activity under
      neural control. This has potential clinical value as a means to create an
      additional striated urethral sphincter.

PMID- 17507042
TI  - Effects of tolterodine on afferent neurotransmission in normal and
      resiniferatoxin treated conscious rats.
AB  - PURPOSE: The beneficial effects of antimuscarinics on detrusor overactivity and
      overactive bladder syndrome are exerted during bladder filling, when there is no
      parasympathetic outflow from the spinal cord. We tested the hypothesis that, if
      tolterodine exerts some of its effects on afferent nerves, the functional
      elimination of C-fiber afferents should affect the actions of the drug on
      urodynamic parameters. MATERIALS AND METHODS: The study was performed in normal
      female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate
      vanilloid sensitive afferent nerves. Tolterodine was given intravenously to
      normal and resiniferatoxin treated animals. To test if tolterodine at the doses
      used affects efferent neurotransmission the drug was given to normal and
      resiniferatoxin treated animals in which detrusor activity was induced by
      apomorphine. RESULTS: In resiniferatoxin treated animals (0.3 mg kg-1
      subcutaneously) the mean micturition interval and volume, and mean residual
      volume increased significantly compared to those in controls. Baseline and
      micturition pressures in control and resiniferatoxin treated animals were
      similar, whereas threshold pressures were higher in resiniferatoxin treated
      animals. In controls 10 microg kg-1 tolterodine administered intravenously
      increased the mean micturition interval, bladder capacity and micturition volume.
      In resiniferatoxin treated rats 1 and 10 microg kg-1 tolterodine increased the
      mean micturition interval, bladder capacity and micturition volume. Subcutaneous
      administration of 100 microg kg-1 apomorphine induced detrusor overactivity in
      all rats. The AUC of intravesical pressure during the initial 10 minutes from the
      start of detrusor overactivity showed no difference between normal and
      resiniferatoxin treated rats with or without tolterodine pretreatment.
      CONCLUSIONS: Tolterodine increased the micturition interval and bladder capacity
      in controls and in resiniferatoxin treated animals, suggesting that these effects
      were exerted independently of resiniferatoxin sensitive afferents. Tolterodine
      did not decrease the contractile effects of apomorphine at the doses used,
      suggesting that the drug had no effect on efferent neurotransmission during
      voiding.

PMID- 17507043
TI  - SAMHO BROTHER benzene ship accident.

PMID- 17507044
TI  - Non-covalent ligand/DNA interactions: minor groove binding agents.
AB  - An understanding of the mechanism by which minor groove binding agents interact
      with DNA has led to the design of agents that can reversibly bind with high
      selectivity to extended DNA target sequences. Simple compounds, such as the
      polypyrroles and the bis-benzimidazoles, have been used as carriers for
      alkylating agents effectively directing alkylation to specific DNA sequences. The
      spectrum of DNA alkylation and mutation by classical alkylators, such as nitrogen
      mustards, has been profoundly modified by such attachment. The observed "side-by
      side" binding of small polypyrrole antibiotics has led to the design of synthetic
      hairpin polyamides with programmable DNA sequence selectivity. These compounds
      are able to compete with natural substrates, such as specific transcription
      factors, and alter gene expression. They are being developed as artificial
      transcription factors, able to deliver activating peptides to specific
      recognition sequences, and as potential protein-DNA dimerization agents. Hairpin
      polyamides are also being used as carriers for the delivery of alkylators to
      defined DNA sites. The degree of control of gene expression thus offered by the
      hairpin polyamides suggests enormous promise for their clinical utility. Recent
      developments with other minor groove binding small molecules and technological
      advances are also discussed.

PMID- 17507045
TI  - [Surgical treatment of cortical and subcortical cavernomas. General principles
      and personal series of 20 cases treated between 2000 and 2006].
AB  - The surgical treatment of cortical or subcortical hemispheric cavernomas is
      founded on a series of questions: Is the cavernoma located in an eloquent or non
      eloquent area? Is the cavernoma tangent to the cortex and visible immediately
      after the dura opening or deep seated in the hemisphere? Does the cavernoma lie
      in the depth of a sulcus and identifiable on the pretrans-sulcal approach MRI?
      Will perilesional tissue have to be removed to cure the epilepsy? What is the
      appropriate technology for each particular case: preoperative functional MRI,
      angiography, preoperative stereotactic guidance, peroperative ultrasonography,
      neuronavigation, peroperative neurophysiology and cortical stimulation,
      preoperative MRI? Based on a personal series of 20 cases operated on between 2000
      and 2006, we describe our personal experience.

PMID- 17507046
TI  - [Epileptogenicity and evaluation of epileptic risk].
AB  - Epilepsy is the more frequent clinical manifestation of hemispheric cavernomas in
      50 to 75% of symptomatic cases; the annual risk of a first seizure is evaluated
      from 1.5 to 2.5%. As for all epileptogenic lesions, many questions arise: Is the
      pathologic tissue or the perilesional cortex responsible for the epileptic
      symptoms? Is the risk related with the topography of the lesion? Is the prognosis
      of the epilepsy related with the number of seizures? Can the epilepsy become drug
      resistant? Can surgical treatment cure the epilepsy? When surgery is indicated,
      should lesionectomy alone or lesionectomy plus perilesional tissue resection be
      performed? The iron and the hemosiderin deposits induce metabolic perturbations
      and tissue reorganization (gliosis and sclerosis) around the cavernoma. These
      cortical modifications seem to be responsible for the epileptic discharges but
      this is difficult to demonstrate. Epileptic discharges have been recorded in the
      perilesional tissue in only one study of the literature. Drug therapy can usually
      control the seizures, but it appears that surgery is more effective when the
      epilepsy is recent and the seizures are not too frequent. For these reasons it
      would appear licit to propose the resection of the lesion when the surgical risk
      is not too great. In case of drug-resistant epilepsy, the same function-targeted
      surgical strategy may be used as for the management of any severe epilepsy.

PMID- 17507047
TI  - [Symptomatic intramedullary arachnoid cyst. Report of two cases and literature
      review].
AB  - OBJECTIVE: The objective of this work is to present and discuss the rare
      situation of curable medullary compression with favorable prognosis. MATERIAL AND
      METHOD: Two cases of thoracic intramedullary arachnoid cysts are described.
      Clinical, paraclinical, therapeutics and outcome features are discussed with a
      review of the literature. RESULTS: Two children, 4 and 8 years old, with an
      uneventful history were admitted for progressive spastic paraparesia. MRI
      demonstrated a thoracic intramedullary cystic lesion at level T3-T4 in both
      patients. The cyst was emptied with partial cyst wall resection via dorsomedial
      myelotomy. The pathology examination confirmed the diagnosis of arachnoid cyst.
      The initial clinical signs resolved completely in both patients. CONCLUSION:
      Thought in children, intramedullary arachnoidian cyst is a potential cause of
      medullary compression. Direct surgery is the treatment of choice.

PMID- 17507048
TI  - [Contribution of molecular genetics in cavernous angiomas].
AB  - In 20% of cases, central nervous system cavernomas are an autosomal dominant
      familial disease. In these cases, lesions are multiple and one or more parents
      suffer of the same affection. Three genes (CCM 1, 2 and 3) have been identified
      since 1999, two on chromosome 7 (one on each arm) and one on the short arm of
      chromosome 3. The role of these genes in normal cerebral angiogenesis is unknown
      today. In clinical practice, molecular tests may be useful in some situations: 1)
      in sporadic cases with a unique lesion, molecular test should not be performed
      since these cases are not genetic; 2) in patients with multiple lesions who have
      an affected relative, the genetic nature of the disease is obvious and molecular
      tests are useful only for genetic counseling; 3) in sporadic cases with multiple
      lesions and no known affected relative, molecular tests can establish the genetic
      nature of the disease and be useful for genetic counseling.

PMID- 17507049
TI  - [Natural history of intramedullary cavernomas. Results of the French Multicentric
      Study].
AB  - INTRODUCTION: The prevalence of cerebral cavernomas is about 0.5% in the general
      population. In contrast, spinal cord cavernomas are considered as rare. The
      objective of this study was to determine the natural history of spinal cord
      cavernomas in a multicentric study. METHODS: Clinical and neuroradiological
      findings were retrospectively collected. Diagnosis was based on pathological
      criteria or magnetic resonance (MR) findings. RESULTS: Fifty-three patients were
      included (26 males, 27 females). Mean age at onset of symptoms was 40.2 years
      (range: 11-80). Initial symptoms were progressive (32) and acute myelopathy (20).
      One patient was asymptomatic. Clinical symptoms were related to spinal cord
      compression (24) and hematomyelia (19). Cavernoma location was dorsal (41) and
      cervical (12.). MR findings consisted of hyperintense signal on T1 and T2
      sequences (19 cases), mixed hyperintense and hypointense signal (33 cases), and
      hypointense signal on T1 and T2 sequences in 1 case. Mean size was 16.3 mm
      (range: 3-54). Forty patients underwent surgical resection. Improvement was
      observed in 20 patients and worsening of neurological symptoms in 11. Length of
      follow up was 7.1 years. At the end of the study, 26 patients were autonomous, 18
      handicapped and 1 bedridden. CONCLUSION: This study provided precise data on the
      clinical and MR patterns of these lesions. The natural history is associated with
      a higher risk of hemorrhage recurrence, but is favorable in many operated
      patients. Microsurgery is the treatment of choice for most of these lesions.

PMID- 17507050
TI  - [Radiosurgery in the treatment of brain cavernomas. Experience with 17 lesions
      treated in 15 patients].
AB  - The aim of this study is to assess the efficiency of radiosurgery (RS) in the
      treatment of brain cavernomas. The series included intra-axial 17 lesions in 15
      patients, 10 women and 5 men. Eleven were infratentorial lesions (brain stem and
      cerebellum) and 6 supratentorial (thalamus, hippocampus, brain cortex and
      paraventricular region). Fifteen lesions bled once or twice. Two lesions revealed
      by focal epilepsy displayed a rim of hemosiderin on MRI. RS was performed for all
      17 lesions. The risk of morbidity was considered too high for surgery in 13
      patients and 2 patients wished to be treated by RS. RS was delivered by a 6 MeV
      linear accelerator with a conic collimators device. Stereotactic localization and
      dosimetry were carried out with STP system 3.O (Fischer-Liebinger TM, Germany).
      Doses ranged between 16 and 23 Gy, the lower doses being delivered to brain stem
      lesions. All the lesions received a single fraction isocentric radiation. Lesion
      volumes ranged between 0.7 and 4.7 cm(3). Twelve lesions disappeared on MRI, the
      volume reduced (50-80%) in 3 lesions, and did not change in 2 lesions. Volume
      reduction was significant (P<0.01, P<0.001). In the follow up, 4 patients
      experienced bleeding, 1 of them died. Edema diagnosed in 2 patients at 3 and 13
      months was treated by corticosteroids. The risk of hemorrhage without treatment
      in this group of patients was estimated about 34.45% a year. Hemorrhage incidence
      observed after RS was 7.17% (significant with P<0.01, P<0.001). At the end of
      follow up, 12 patients were symptom-free, 2 had sequels from bleeding, 1 patient
      died. Radiosurgery is an efficient treatment of cavernomas leading to a total
      disappearance of 70% of the lesions and significantly reducing the risk of new
      hemorrhages.

PMID- 17507051
TI  - [Pineal cyst: usefulness of endoscopic treatment].
AB  - Glial cysts of the pineal gland are usually benign and asymptomatic. They develop
      from the pineal parenchyma and contain liquid. The diagnosis is made by magnetic
      resonance imaging. In contrast large cysts can be symptomatic due to compression
      of the aqueduct of Sylvius, compression of the midbrain tectum or mass effect in
      the posterior fossa. We report the case of a symptomatic cyst treated by an
      endoscopic procedure.

PMID- 17507052
TI  - [Open kyphoplasty for management of metastatic spine fracture].
AB  - INTRODUCTION: Metastatic spine fractures are very frequent, often occurring in
      patients with severe medical conditions. Open kyphoplasty and vertebroplasty are
      part of the classic management of this of fracture. In certain conditions such as
      spinal cord compression caused by epidural metastatic cancer or collapse of the
      vertebral body implying a local kyphosis, surgery should allow decompression of
      the spinal cord and stabilisation of the spine in a simple act. The purpose of
      this study is to assess a surgical technique combining surgical decompression by
      laminectomy frequently associated with posterior transpedicular instrumentation
      and at the same time, an open kyphoplasty to stabilize the anterior part of the
      spine. MATERIAL AND METHODS: The same procedure was performed in 14 patients
      during an 18-month period. The average age of the patients was 54 years. All
      patients suffered severe pain before the surgical procedure (VSA mean: 7).
      Neurological deficiency was noted in 10 of the 14 patients with this spinal cord
      compression. Nineteen vertebrae were treated; a short posterior instrumentation
      was necessary in 11 patients. The average operative time was 90 minutes. Of the
      patients with neurological deficiency, the clinical status improved after surgery
      in all. The average VSA of this series 3 days after surgery was 2. The mean
      quantity of PMMA injected was 7 cc. Two PMMA leaks, one in the intervertebral
      disc and one forward, were identified on the postoperative CT scan. The average
      hospital stay was 7 days. CONCLUSION: This procedure enables surgical
      decompression, vertebral body consolidation and consequently spinal stabilization
      of the spine. We did not have any complications related to this procedure which,
      particularly for the elderly population, is an attractive alternative to major
      surgery such as vertebrectomy.

PMID- 17507053
TI  - [Results of surgical treatment].
AB  - In this chapter we report the results of the main papers of the international
      literature, but it is difficult to make an objective synopsis because only the
      best results are published and failure and complications remain confidential. Few
      papers describe "general complications" as thrombo phlebitis, wound infection,
      cardio respiratory insufficiency... which are probably as frequent as for all
      intracranial or spinal surgical procedures. The postoperative neurological status
      depends essentially on the location of the lesion. In non eloquent area, the
      postoperative neurological status is almost always excellent. But in a
      hemispheric functional area, basal ganglia and brain stem it is frequent to
      observe neurological sequellae; in the better series of the literature, 80% of
      the patients achieve a good outcome equivalent to or better than before the
      operation, but 20% are worsened. It is important to remember this fact before
      discussing the surgical indication. The risk of hemorrhage disappears after total
      surgical resection; and it is one of the benefits of the treatment, but this
      objective can be reached only when the lesion is unique. The risk persists in
      multiple forms and "de novo" cavernomas are always possible especially in
      familial forms. The main benefit is the treatment of epilepsy for seizure
      control. In case of good concordance between the location of the cavernoma and
      the clinical and electrical data, lesionectomy alone or lesionectomy with
      resection of the perilesional hemosiderin ring provide good results. In the event
      of severe epilepsy without good concordance between the site of the cavernoma and
      symptoms, the surgical approach may be functional and outcome less satisfactory.

PMID- 17507054
TI  - [Deep-seated (corpus callosum, intraventricular, basal ganglia and insula) and
      brain stem cavernous angiomas. Experience in Brazil].
AB  - With a review of the literature, we report our experience with surgical treatment
      of deep-seated cavernomas (intraventricular, of the corpus callosum, the capsula
      interna, the insula and the brain stem). Outcome was good in all nine patients
      after surgery for deep-seated brain cavernomas. There we also 13 cases of the
      brain stem cavernomas treated surgically. Of them, nine patients were stabilized
      or improved, one patient worsened, one patient died and two were lost to follow
      up. Whatever the location, surgery should only concern symptomatic or hemorrhagic
      lesions close to the pia-matter or the ependyma as well as those covered by a
      thin layer of parenchyma. Neuronavigation and microsurgical procedures are
      essential in the treatment of deep-seated cavernomas.

PMID- 17507055
TI  - [Radiology of central nervous system cavernomas].
AB  - MRI is the best radiological technique to explore cavernomas, vascular
      malformations affecting the entire central nervous system. The presence of blood
      degradation products produces a specific aspect which enables excellent contrast
      resolution. Certain diagnosis can be established with MRI which can also be used
      to follow growth and modifications, particularly in familial forms. In the
      emergency setting, the first exam is often a CT-scan for patients presenting
      acute neurological sign(s) and/or with a clinical suspicion of hemorrhagic
      stroke. Angiography is generally not contributive because cavernomas are occult
      vascular malformations. Nevertheless, this exam is often necessary when an
      associated vascular abnormality is suspected, particularly a developmental venous
      abnormality.

PMID- 17507056
TI  - [Natural history of cavernomas of the central nervous system].
AB  - We present a critical review of the literature on the central nervous system
      cavernomas in order to highlight their natural history and to define the most
      appropriate management of these rare lesions. The prevalence is now estimated
      from 0.3 to 0.7% in the general population without any significant difference by
      gender; 25% of cases are pediatric. Two forms of the disease can be described:
      sporadic forms in 80% of cases, characterized by isolated or rare lesions and
      familial dominant autosomic forms characterized by multiple and evolutive
      lesions. The incidence is not well known, the consultation of the French PMSI
      database suggests that 50 to 100 cases are operated on each year (1 to 2 per
      million). Cavernomas are dynamic lesions: growing in many cases, seldom remaining
      quiescent and disappearing in rare cases. The anatomical evolution is more
      pejorative in familial forms. "De novo" cases are now well known, either in
      familial or sporadic forms and after radiotherapy. Many lesions are totally
      asymptomatic, but the frequency of symptomatic forms is debated in the literature
      from 3 to 90%... The hemorrhagic risk is evaluated from 0,5 to 3% each year,
      depending on the localization, and the risk of rebleeding is more important but
      not well known. The epileptic risk is correlated to the localization, more
      frequent for temporal and frontal lesions from 4,5 to 11% each year, but these
      data are controversial. The natural history depends on the topography:
      hemispheric, deep-seated, brain stem, cerebellum or intramedullary and in
      pediatric situations. Each situation will be treated in this report.

PMID- 17507057
TI  - [Central nervous system cavernomas in children].
AB  - Cavernomas represent 1.7 to 18% of all vascular malformations in children and 25%
      are observed in children under 18 years of age. Cases observed in neonates and
      infants have been published, but the mean age varies from 9.1 to 10.2 years.
      There is no predominance between boys and girls. CLINICAL PRESENTATION: In
      children, hemorrhage is a common manifestation with an incidence varying from
      27.3 to 78% versus 8 to 37% in adult patients. Isolated headaches occur in 2.8%
      of patients and elevated ICP is observed in 20.1%. Epilepsy is reported in 16 to
      60% of children, depending on the series. Neurological deficits are observed in
      22.7% of patients and are more severe for deep-seated and brainstem cavernoma.
      About 14.2% of the cases are discovered fortuitously in asymptomatic patients.
      Spinal cord deficits are observed in 5% of the cases. LOCATION: Using data in the
      literature plus our personal series of 57 cases, 79.4% of lesions are in the
      supratentorial compartment and 20.6% in the posterior fossa, the majority located
      in the brainstem, most of them in the pons. Spinal cord cavernomas represent 5%
      and multiples cavernomas (12.6%) of the reviewed cases. MANAGEMENT: Appropriate
      management of cavernomas has long been a subject of much debate. Today, a
      consensus has been reached to favor medical management of asymptomatic and non
      hemorrhagic lesions and surgical management of symptomatic and/or hemorrhagic
      cavernomas whatever the localization. Progress in neuroimaging, surgical mapping,
      intraoperative monitoring and microsurgical techniques has greatly contributed to
      improved approach to those lesions. RESULTS: Results obtained in 217 cases were
      reviewed. Near 70% of the children are neurologically intact, 19.3% are improved
      or stable, 2.7% worsened and 1.13% died. Results for epilepsy are very
      encouraging, surgery is efficient in almost all the children except for temporal
      lobe cavernomas where invasive presurgical evaluation is recommended. Deep-seated
      and brainstem cavernomas can safely be removed in most of the cases. Only two
      children died from recurrent hemorrhage due to residual lesions.

PMID- 17507058
TI  - Intraindividual variability in neurocognitive speed: a comparison of Parkinson's
      disease and normal older adults.
AB  - We examined whether intraindividual variability of neurocognitive speed, or
      inconsistency, is greater in stages of Parkinson's disease (PD) as compared to a
      matched group of normal older adults. Intraindividual variability was assessed
      using four reaction time (RT) (simple and complex) tasks. We examined three sets
      of correlates: executive functioning (Stroop (interference index), Trail Making
      Test (Part B), and Digit Ordering Test), finger tapping speed, and gait speed.
      The participants were matched on age, sex, and education, and did not differ in
      global cognitive functioning. There were 50 patients with a clinical diagnosis of
      idiopathic PD (29 men and 21 women) who ranged from 65 to 84 years (M=71.5,
      S.D.=4.7) and 48 matched healthy older adults who ranged from 65 to 84 years
      (M=71.5, S.D.=4.9). Multiple analyses of variance showed that the PD patients
      were slower on all three complex RT tasks, and more inconsistent than healthy
      older adults on the most complex (eight-choice) RT task. Individuals with
      advanced disease had slower neurocognitive speed and more inconsistency than
      patients with earlier stage PD. Poorer executive functioning was associated with
      slower neurocognitive performance in healthy older adults, mild PD patients, and
      especially severe PD patients. Greater inconsistency in speed was related to
      poorer executive functioning in late stage PD (for the most complex task) and in
      healthy older adults (for the simplest task), indicating that motor and cognitive
      domains have functional coupling (i.e., as one becomes compromised so does the
      other). Intraindividual variability was not correlated with tapping speed and
      gait speed in any group. Executive functioning and neurocognitive speed may be
      valid and distinct clinical markers of disease progression in PD.

PMID- 17507059
TI  - Prism adaptation in spinocerebellar ataxia type 2.
AB  - Patients with spinocerebellar ataxia type 2 (SCA2), develop severe pontine
      nuclei, inferior olives, and Purkinje cell degeneration. This form of autosomal
      dominant cerebellar ataxia is accompanied by progressive ataxia and dysarthria.
      Although the motor dysfunction is well characterized in these patients, nothing
      is known about their motor learning capabilities. Here we tested 43 SCA2 patients
      and their matched controls in prism adaptation, a kind of visuomotor learning
      task. Our results show that their pattern of brain damage does not entirely
      disrupt motor learning. Rather, patients had impaired adaptation decrement, but
      surprisingly a normal aftereffect. Moreover, the mutation degree could
      discriminate the degree of adaptation. This pattern could reflect the net
      contribution of two adaptive mechanisms: strategic control and spatial
      realignment. Accordingly, SCA2 patients show an impaired strategic control that
      affects the adaptation rate, but a normal spatial realignment measured through
      the aftereffect. Our results suggest that the neural areas subserving spatial
      realignment are spared in this form of spinocerebellar ataxia.

PMID- 17507061
TI  - Comparative analysis of anxiety-like behaviors and sensorimotor functions in two
      rat mutants, ci2 and ci3, with lateralized rotational behavior.
AB  - There is increasing evidence that developmental anomalies of cerebral asymmetry
      are involved in the etiology of psychiatric disorders, including schizophrenia,
      depression and anxiety. Thus, rodents with abnormal cerebral lateralization are
      interesting tools to study the association between such anomalies and behavioral
      dysfunction. The most studied indicator of cerebral asymmetry in the rat is that
      of circling or rotational behavior. We have recently described two rat mutants,
      ci2 and ci3, in which lateralized rotational behavior occurs either spontaneously
      or in response to external stimuli, such as new environment or handling. While
      cochlear and vestibular defects are found in ci2 rats, ci3 rats do not exhibit
      any inner ear abnormalities. The abnormal motor response to external stimuli
      raised the possibility that the circling rat mutants may be more likely to
      express anxiety-related behavior in tests of emotionality. In the present study,
      we characterized anxiety-related behaviors of ci2 and ci3 rats in the open field,
      elevated plus-maze and light/dark exploration test. Furthermore, sensorimotor
      functions of these rats were evaluated by the rotarod, accelerod and wire hang
      tests. Heterozygous (ci2/+) littermates or rats of the respective background
      strains (LEW, BH.7A) were used as controls. In contrast to our expectation, both
      mutants demonstrated less anxiety-related behavior than controls in tests of
      emotionality. Ci3 rats exhibited normal sensorimotor functions, whereas marked
      impairment was observed in ci2 rats, which is most likely a consequence of the
      vestibular dysfunction in these animals. The acoustic startle response (ASR) and
      prepulse inhibition of ASR did not differ between ci3 rats and controls. The
      reduced emotionality of the mutant rats indicated by the present experiments may
      not be specifically linked to anxiety per se, but is maybe more reflective of
      impulsivity or the inability to normally perceive or process potentially
      threatening situations. Based on previous findings of dysfunctions of the central
      dopamine system in ci2 and ci3 mutant rats, we assume that alterations in
      dopaminergic activity are involved in the maladaptive behavior observed in the
      present study.

PMID- 17507060
TI  - Impaired spatial and non-spatial configural learning in patients with hippocampal
      pathology.
AB  - The hippocampus has been proposed to play a critical role in memory through its
      unique ability to bind together the disparate elements of an experience. This
      hypothesis has been widely examined in rodents using a class of tasks known as
      "configural" or "non-linear", where outcomes are determined by specific
      combinations of elements, rather than any single element alone. On the basis of
      equivocal evidence that hippocampal lesions impair performance on non-spatial
      configural tasks, it has been proposed that the hippocampus may only be critical
      for spatial configural learning. Surprisingly few studies in humans have examined
      the role of the hippocampus in solving configural problems. In particular, no
      previous study has directly assessed the human hippocampal contribution to non
      spatial and spatial configural learning, the focus of the current study. Our
      results show that patients with primary damage to the hippocampus bilaterally
      were similarly impaired at configural learning within both spatial and non
      spatial domains. Our data also provide evidence that residual configural learning
      can occur in the presence of significant hippocampal dysfunction. Moreover,
      evidence obtained from a post-experimental debriefing session suggested that
      patients acquired declarative knowledge of the underlying task contingencies that
      corresponded to the best-fit strategy identified by our strategy analysis. In
      summary, our findings support the notion that the hippocampus plays an important
      role in both spatial and non-spatial configural learning, and provide insights
      into the role of the medial temporal lobe (MTL) more generally in incremental
      reinforcement-driven learning.

PMID- 17507062
TI  - 13CO2 as a universal metabolic tracer in isotopologue perturbation experiments.
AB  - A tobacco plant was illuminated for 5h in an atmosphere containing (13)CO(2) and
      then maintained for 10 days under standard greenhouse conditions. Nicotine,
      glucose, and amino acids from proteins were isolated chromatographically.
      Isotopologue abundances of isolated metabolites were determined quantitatively by
      NMR spectroscopy and mass spectrometry. The observed non-stochastic isotopologue
      patterns indicate (i) formation of multiply labeled photosynthetic carbohydrates
      during the (13)CO(2) pulse phase followed by (ii) partial catabolism of the
      primary photosynthetic products, and (iii) recombination of the (13)C-labeled
      fragments with unlabeled intermediary metabolites during the chase period. The
      detected and simulated isotopologue profiles of glucose and amino acids reflect
      carbon partitioning that is dominated by the Calvin cycle and
      glycolysis/glucogenesis. Retrobiosynthetic analysis of the nicotine pattern is in
      line with its known formation from nicotinic acid and putrescine via aspartate,
      glyceraldehyde phosphate and alpha-ketoglutarate as basic building blocks. The
      study demonstrates that pulse/chase labeling with (13)CO(2) as precursor is a
      powerful tool for the analysis of quantitative aspects of plant metabolism in
      completely unperturbed whole plants.

PMID- 17507063
TI  - Pensteminoside, an unusual catalpol-type iridoid from Penstemon gentianoides HBK
      (Plantaginaceae).
AB  - From the MeOH and ethyl acetate extracts of aerial parts of Penstemon
      gentianoides HBK (Plantaginaceae) an unusual iridoid of the catalpol-type, was
      isolated and characterized as pensteminoside: (8-O-trans-cinnamoyl, 6-hydroxy, 1
      [beta-D-glucopyranoside-6'-O-((4''-hydroxy)-cinnamoyl)]-catalpol) was isolated,
      along with the known iridoids: plantarelanoside and globularisicin, the flavone:
      luteolin and diosmetin, as well the phenylpropanoids, verbascoside and
      martynoside. Their structures were established by 1D and 2D NMR spectroscopic
      analyses.

PMID- 17507064
TI  - Consultants' attitudes to clinical governance: barriers and incentives to
      engagement.
AB  - OBJECTIVE: To explore medical specialists' attitudes to clinical governance in
      acute hospitals and factors influencing these attitudes. METHODS: A semi
      structured interview study with a purposeful sample of 24 medical specialists
      from two contrasting hospitals. Hospital A had a low level of consultant
      involvement in quality improvement initiatives and Hospital B had higher levels
      of engagement. RESULTS: Specialists from both hospitals acknowledged that quality
      improvement was a major part of their role. Among specialists from Hospital A,
      the lack of a commonly held focus on quality-improvement, poor inter-professional
      relationships and little clinical engagement in management were the main factors
      generating negative attitudes towards clinical governance. Effective
      communication of the hospital's goal of continuous quality improvement to all
      staff groups, a sense of being able to get issues affecting the quality of care
      heard by senior management, and a perception that there were clear structures and
      processes to support clinical governance, were factors that resulted in a more
      positive attitude to clinical governance among specialists in Hospital B.
      Specialists from both hospitals identified lack of time across all professional
      groups and availability of accurate data as barriers to involvement in clinical
      governance activities. CONCLUSION: The cultural context, level of technical
      support available, ability to communicate clear goals and strategies and the
      presence of structures to support delivery, all contribute to shaping
      specialists' attitudes to clinical governance and in turn influence levels of
      engagement and ultimately the success of quality improvement initiatives.

PMID- 17507065
TI  - Extension of indoor residual spraying for malaria control into high transmission
      settings in Africa.
AB  - Contrary to previous consensus, a recent WHO statement recommends a more dominant
      role for indoor residual spraying (IRS) in malaria control in high transmission
      settings of sub-Saharan Africa and re-emphasises the role of DDT. We review the
      issues related to this change in recommendation. In high transmission settings,
      IRS must be implemented indefinitely and at high quality to achieve control. As
      current infrastructure limitations and unpredictable funding make this unlikely,
      each country must carefully consider the role of IRS. There remains a need to
      support ongoing insecticide-treated net scale-up. Insecticide choice is hampered
      by the lack of economic costing data.

PMID- 17507066
TI  - The other 'neglected' eradication programme: achieving the final mile for Guinea
      worm disease eradication?
AB  - Guinea worm disease is one of two diseases targeted for eradication, the other
      being polio. Since the late 1980s, the number of new cases per year has been
      reduced from approximately one million to some 25 000 in 2006. However, there was
      an increase from 2005 owing to improved surveillance in Sudan and problems in
      Ghana. The International Commission argues that more resources are required to
      ensure that the goal of eradication is completed. Elimination of transmission
      throughout Asia has now been confirmed and the disease is now confined to a small
      number of African countries requiring increased efforts to achieve the global
      goal.

PMID- 17507067
TI  - Economic burden of neurocysticercosis: results from Peru.
AB  - Neurocysticercosis (NCC) is a major cause of neurological morbidity in the
      developing world. This study aimed to assess the treatment costs and productivity
      losses associated with NCC in Peru. NCC patients were identified through
      retrospective chart analysis. Patients meeting inclusion criteria were
      interviewed in order to obtain data on symptom history, treatment costs,
      productivity losses and health service utilisation patterns. These data were
      modelled to determine average treatment costs and productivity losses over 2
      years. Our findings show that treatment costs and productivity losses consume 54%
      of an annual minimum wage salary during the first year of treatment and 16%
      during the second year. Diagnosis (36%) and drug therapy (27%) represent the most
      expensive healthcare-related costs. These costs are prohibitive for some-8% of
      our study sample had no diagnostic tests during their first 6 months of disease,
      and two-thirds of those who delayed treatment reportedly did so due to their
      inability to pay. Two-thirds of wage-earners lost their jobs owing to NCC and
      only 61% were able to re-engage in wage-earning activities. This study highlights
      the need to expand financial coverage to ensure the poor have access to health
      services and do not become further impoverished.

PMID- 17507068
TI  - Biological control through provision of additional food to predators: a
      theoretical study.
AB  - In this paper we analyze a variation of a standard predator-prey model with type
      II functional response which represents predator-prey dynamics in the presence of
      some additional food to the predator. The aim is to study the consequences of
      providing additional food on the system dynamics. We conclude that handling times
      for the available foods play a key role in determining the eventual state of the
      ecosystem. It is interesting to observe that by varying the quality and quantity
      of additional food we can not only control and limit the prey, but also limit and
      eradicate the predators. In the context of biological pest control, the results
      caution the manager on the choice of quality and quantity of the additional food
      used for this purpose. An arbitrary choice may have opposite effects leading to
      increase in pest concentration and eradication of the predator. This study offers
      insight into the possible management strategies that involve manipulation of
      quality and supply level of additional food to predators, for the benefit of
      biological control. The theoretical conclusions agree with results of some
      practical biological control experiments.

PMID- 17507069
TI  - Localization and irregular distribution of Na,K-ATPase in myelin sheath from rat
      sciatic nerve.
AB  - Sodium, potassium adenosine triphosphatase (Na,K-ATPase) is a membrane-bound
      enzyme that maintains the Na(+) and K(+) gradients used in the nervous system for
      generation and transmission of bioelectricity. Recently, its activity has also
      been demonstrated during nerve regeneration. The present study was undertaken to
      investigate the ultrastructural localization and distribution of Na,K-ATPase in
      peripheral nerve fibers. Small blocks of the sciatic nerves of male Wistar rats
      weighing 250-300g were excised, divided into two groups, and incubated with and
      without substrate, the para-nitrophenyl phosphate (pNPP). The material was
      processed for transmission electron microscopy, and the ultra-thin sections were
      examined in a Philips CM 100 electron microscope. The deposits of reaction
      product were localized mainly on the axolemma, on axoplasmic profiles, and
      irregularly dispersed on the myelin sheath, but not in the unmyelinated axons. In
      the axonal membrane, the precipitates were regularly distributed on the
      cytoplasmic side. These results together with published data warrant further
      studies for the diagnosis and treatment of neuropathies with compromised Na,K
      ATPase activity.

PMID- 17507070
TI  - Tetrodotoxin and its analogue 6-epitetrodotoxin in newts (Triturus spp.; Urodela,
      Salamandridae) from southern Germany.
AB  - Tetrodotoxin (TTX) and its analogue 6-epitetrodotoxin (6-epiTTX) were
      quantitatively assayed in 59 newts representing four Triturus species (Triturus
      alpestris, Triturus cristatus, Triturus helveticus, Triturus vulgaris) from
      southern Germany by a post-column fluorescent-HPLC system. Both toxins were
      detected in only 15 specimens of the four species. The toxins levels varied
      considerably among individuals (TTX: 0.11-9.0microg/g; 6-epiTTX: 0.05
      17.0microg/g). 6-epiTTX was found to be the major component.

PMID- 17507071
TI  - DNA/MVA HIV-1/AIDS vaccine elicits long-lived vaccinia virus-specific immunity
      and confers protection against a lethal monkeypox challenge.
AB  - Modified vaccinia Ankara (MVA) is being tested in humans as an alternative to the
      current smallpox vaccine Dryvax. Here, we compare the magnitude and longevity of
      protective immune responses elicited by a DNA/MVA HIV-1 vaccine with those
      elicited by Dryvax using a monkeypox virus/macaque model. The DNA/MVA vaccine
      elicited similar levels of vaccinia virus (VV)-specific antibody and 5-10-fold
      lower levels of VV-specific cellular responses than Dryvax. This MVA-elicited
      cellular and humoral immunity was long-lived. A subset of the DNA/MVA- and Dryvax
      vaccinated macaques were subjected to a lethal monkeypox virus challenge at 3
      years after vaccination. All of the vaccinated monkeys survived, whereas the
      unvaccinated controls succumbed to monkeypox. The viral control correlated with
      early postchallenge levels of monkeypox-specific neutralizing antibody but not
      with VV-specific cellular immune response. Thus, our results demonstrate the
      elicitation of long lasting protective immunity for a lethal monkeypox challenge
      by a DNA/MVA HIV-1 vaccine.

PMID- 17507072
TI  - Comparative analysis of the alphavirus-based vectors expressing Rift Valley fever
      virus glycoproteins.
AB  - During the last decade, alphaviruses became widely used for expression of
      heterologous genetic information and development of recombinant vaccines against
      a variety of human and animal pathogens. In this study, we compared a number of
      vectors based on the genome of Sindbis (SINV) and Venezuelan equine encephalitis
      (VEEV) viruses for their ability to express the Rift Valley fever virus (RVFV)
      envelope glycoprotein Gn and induce a protective immune response against RVFV
      infection. Our results suggest that (i) application of VEEV-based expression
      systems appears to be advantageous, when compared to similar systems designed on
      the basis of the SINV genome. (ii) Alphavirus-specific E3 and E2 proteins and
      furin-specific cleavage sites can be used for engineering secreted forms of the
      proteins. (iii) Alphaviruses can be modified for expression of the large
      fragments of heterologous proteins on the surface of chimeric, infectious viral
      particles. Thus, alphavirus-based expression systems may have the potential for a
      broader application beyond their current use as replicons or double-subgenomic
      vectors.

PMID- 17507073
TI  - Oral administration of live virus protects susceptible mice from developing
      Theiler's virus-induced demyelinating disease.
AB  - Intracerebral infection of susceptible mouse strains with Theiler's murine
      encephalomyelitis virus (TMEV) results in an immune-mediated demyelinating
      disease similar to human multiple sclerosis. TMEV infection is widely spread via
      fecal-oral routes among wild mouse populations, yet these infected mice rarely
      develop clinical disease. Oral vaccination has often been used to protect the
      host against many different infectious agents, although the underlying protective
      mechanism of prior oral exposure is still unknown. To understand the mechanisms
      involved in protection from demyelinating disease following previous oral
      infection, immune parameters and disease progression of mice perorally infected
      with TMEV were compared with those of mice immunized intraperitoneally following
      intracerebral infection. Mice infected perorally, but not intraperitoneally,
      prior to CNS viral infection showed lower chronic viral persistence in the CNS
      and reduced TMEV-induced demyelinating disease. However, a prolonged period of
      post-oral infection was necessary for effective protection. Mice orally pre
      exposed to the virus displayed markedly elevated levels of antibody response to
      TMEV in the serum, although T cell responses to TMEV in the periphery were not
      significantly different between perorally and intraperitoneally immunized mice.
      In addition, orally vaccinated mice showed higher levels of early CNS
      infiltration of B cells producing anti-TMEV antibody as well as virus-specific
      CD4(+) and CD8(+) T cells in the CNS compared to intraperitoneally immunized
      mice. Therefore, the generation of a sufficient level of protective immune
      responses appears to require a prolonged time period to confer protection from
      TMEV-induced demyelinating disease.

PMID- 17507075
TI  - Relationships between Bacteroides 16S rRNA genetic markers and presence of
      bacterial enteric pathogens and conventional fecal indicators.
AB  - Occurrence and prevalence of different bacterial enteric pathogens as well as
      their relationships with conventional (total and fecal coliforms) and alternative
      fecal indicators (host-specific Bacteroides 16S rRNA genetic markers) were
      investigated for various water samples taken from different sites with different
      degrees of fecal contamination. The results showed that a wide range of bacterial
      pathogens could be detected in both municipal wastewater treatment plant samples
      and in surface water samples. Logistic regression analysis revealed that total
      and human-specific Bacteroides 16S rRNA genetic markers showed significant
      predictive values for the presence of Escheriachia coli O-157, Salmonella, heat
      labile enterotoxin (LT) of enterotoxigenic E. coli (ETEC), and heat-stable
      enterotoxin for human (STh) of ETEC. The probability of occurrence of these
      pathogenic bacteria became significantly high when the concentrations of human
      specific and total Bacteroides 16S rRNA genetic markers exceeded 10(3) and 10(4)
      copies/100 mL. In contrast, Clostridium perfringens was detected at high
      frequency regardless of sampling sites and levels of Bacteroides 16S rRNA genetic
      markers. No genes related to Shigella spp., Staphylococcus aureus and Vibrio
      cholerae were detected in any samples analyzed in this study. Conventional
      indicator microorganisms had low levels of correlation with the presence of
      pathogens as compared with the alternative fecal indicators. These results
      suggested that real-time PCR-based measurement of alternative Bacteroides 16S
      rRNA genetic markers was a rapid and sensitive tool to identify host-specific
      fecal pollution and probably associated bacterial pathogens. However, since one
      fecal indicator might not represent the relative abundance of all pathogenic
      bacteria, viruses and protozoa, combined application of alternative indicators
      with conventional ones could provide more comprehensive pictures of fecal
      contamination, its source and association with pathogenic microorganisms.

PMID- 17507074
TI  - Functional genomics analyses of differential macaque peripheral blood mononuclear
      cell infections by human immunodeficiency virus-1 and simian immunodeficiency
      virus.
AB  - The pathogenicity of the primate lentiviruses, human, and simian immunodeficiency
      viruses, is host-specific. Previous studies indicated that the highly pathogenic
      human lentivirus HIV-1 has markedly reduced pathogenicity compared to the
      pathogenic simian lentivirus SIV in pigtail macaques (Macaca nemestrina). We
      therefore hypothesized that the pigtail macaque peripheral blood mononuclear
      cells (mPBMCs) would respond differently to infections of HIV-1 and pathogenic
      SIV. To elucidate the cellular responses to the infections of HIV-1 and SIV, we
      infected mPBMC with these two viruses. Like infections in vivo, HIV-1 and SIV
      demonstrated distinct replication kinetics in mPBMCs, with HIV-1 replicating at
      significantly lower levels. Similarly, gene expression profiling facilitated by
      macaque-specific oligonucleotide microarrays also revealed distinct expression
      patterns of genes between the HIV-1- and SIV-infected mPBMCs; in particular,
      genes associated with the antigen presentation, T cell receptor, ERK/MAPK
      signaling, Wnt/beta-catenin signaling, and natural killer cell signaling pathways
      were differentially regulated between these two viruses. Most interestingly,
      despite the lower levels of replication, HIV-1 triggered a more robust regulation
      of immune response genes early after infection; the converse was true in SIV
      infected mPBMCs. Our results therefore suggest that macaques may be controlling
      the infection of HIV-1 at an early stage through coordinated regulation of host
      defense pathways.

PMID- 17507076
TI  - The association between carotid intima-media thickness and sciatica.
AB  - OBJECTIVE: Both clinical and epidemiologic studies have shown an association
      between atherosclerotic changes in the aorta or lumbar arteries and lumbar disc
      degeneration. However, the association between atherosclerosis and sciatica
      remains unknown. The aim of this study was to investigate the association between
      carotid intima-media thickness and sciatica. METHODS: The target population
      consisted of people aged 45 to 74 years, who had participated in a Finnish
      nationwide population study during the period 2000 to 2001 and lived within 200
      km of the 6 study clinics. Of the 1867 eligible subjects, 1386 (74%) were
      included in the study. We used high-resolution B-mode ultrasound imaging to
      measure intima-media thickness, and local or radiating low back pain was
      determined by a standard interview and clinical signs of sciatica through a
      physician's clinical examination. RESULTS: Carotid intima-media thickness was
      associated with continuous radiating low back pain and with a positive unilateral
      clinical sign of sciatica among men only. After adjustment for potential
      confounders, each standard deviation (0.23 mm) increment in carotid intima-media
      thickness showed an odds ratio of 1.6 (95% confidence interval 1.1-2.3) for
      continuous radiating low back pain and 1.7 (95% confidence interval 1.3-2.1) for
      a positive unilateral clinical sign of sciatica. Carotid intima-media thickness
      was not associated with local low back pain. CONCLUSION: Sciatica may be a
      manifestation of atherosclerosis, or both conditions may share common risk
      factors.

PMID- 17507077
TI  - Gap junctional proteins of animals: the innexin/pannexin superfamily.
AB  - There has been some controversy as to whether vertebrate pannexins are related to
      invertebrate innexins. Using statistical, topological and conserved sequence
      motif analyses, we establish that these proteins belong to a single superfamily.
      We also demonstrate the occurrence of large homologues with C-terminal proline
      rich domains that may have arisen by gene fusion events. Phylogenetic analyses
      reveal the orthologous and paralogous relationships of these homologues to each
      other. We show that different sets of orthologous paralogues underwent sequence
      divergence at markedly different rates, suggesting differential pressures through
      evolutionary time promoting or restricting sequence divergence. We further show
      that the first 2 TMS-containing halves of these homologues underwent sequence
      divergence more slowly than the second 2 TMS-containing halves and analyze these
      differences. These bioinformatic analyses should serve as useful guides for
      future studies of structure, function and evolutionary aspects of this important
      superfamily.

PMID- 17507078
TI  - Gap junctional complexes: from partners to functions.
AB  - Gap junctions (GJ), specialised membrane structures that mediate cell-to-cell
      communication in almost all animal tissues, are composed of intercellular channel
      forming integral membrane proteins termed connexins (Cxs), innexins or pannexins.
      The activity of these channels is closely regulated, particularly by
      intramolecular modifications as phosphorylation of proteins, via the formation of
      multiprotein complexes where pore-forming subunits bind to auxiliary channel
      subunits and associate with scaffolding proteins that play essential roles in
      channel localization and activity. Scaffolding proteins link signalling enzymes,
      substrates, and potential effectors (such as channels) into multiprotein
      signalling complexes that may be anchored to the cytoskeleton. Protein-protein
      interactions play essential roles in channel localization and activity and,
      besides their cell-to-cell channel-forming functions, gap junctional proteins now
      appear involved in different cellular functions (e.g. transcriptional and
      cytoskeletal regulation). The present review summarizes the recent progress
      regarding the proteins capable of interacting with junctional proteins and their
      functional importance.

PMID- 17507080
TI  - Connexin-dependent transcellular transcriptomic networks in mouse brain.
AB  - Microarray experiments have generally focused on magnitude of gene expression
      changes in pathological conditions, thereby using the method as a high throughput
      screen to identify candidate marker genes and/or to validate phenotypic
      differences. We have used novel strategies to extract additional information from
      array studies, including expression variability and coordination, from which
      organizational principles of transcriptomes are emerging. We have reported that
      the expression level, variability and coordination of numerous genes are
      regulated in brains of connexin43 null (Gja1(-/-)) mouse with respect to
      wildtype. Moreover, expression coordination with Gja1 in wildtype largely
      predicted the expression regulation in Gja1(-/-) tissues. We now report a
      remarkable overlap between regulations in Gja1(-/-) and connexin32 null (Gjb1(-/
      )) brains, and that both differ markedly from those in connexin36 null (Gja9(-/
      )) brain. Since in brain these three connexins are expressed in different cell
      types (Cx43 in astrocytes, ependymal and vascular cells, Gjb1 in
      oligodendrocytes, and Cx36 in neurons and microglia), and because astrocytes and
      oligodendrocytes (and possibly neurons and microglia) may form syncytia coupled
      by gap junction channels, these observations suggest the existence of distinct
      connexin-dependent panglial and neuronal transcriptomic networks. Such networks,
      where linkage partners are rearranged and strengths modified in brains of
      knockouts, may explain downstream and parallel "ripples" of phenotypic change
      resulting from single gene manipulations as illustrated by alterations in
      transcription factor networks resulting from deletion of Gja1 or Gjb1. The
      transcription factors also formed network hubs with genes from other functional
      categories, thus allowing regulation of one functional pathway through
      manipulation of another.

PMID- 17507079
TI  - Gap junction channel gating modulated through protein phosphorylation.
AB  - As a ubiquitous post-translation modification process, protein phosphorylation
      has proven to be a key mechanism in regulating the function of several membrane
      proteins, including transporters and channels. Connexins, pannexins, and innexins
      are protein families that form gap junction channels essential for intercellular
      communication. Connexins have been intensely studied, and most of their isoforms
      are known to be phosphorylated by protein kinases that lead to modifications in
      tyrosine, serine, and threonine residues, which have been reported to affect, in
      one way or another, intercellular communication. Despite the abundant reports on
      changes in intercellular communication due to the activation or inactivation of
      numerous kinases, the molecular mechanisms by which phosphorylation alters
      channel gating properties have not been elucidated completely. Hence, this
      chapter will cover some of the current, relevant research that attempt to explain
      how phosphorylation triggers and/or modulates gap junction channel gating.

PMID- 17507081
TI  - Healing of vulvo-vaginal radionecrosis following revascularization.
AB  - BACKGROUND: Invasive cancers of the vagina and vulva are treated with radiation
      based therapy when proximity of the bladder and/or rectum precludes conservative
      surgical resection. Patient factors affect non-malignant tissue tolerance to
      radiation exposure. CASE: A smoker with atherosclerotic disease developed tissue
      necrosis and the worsening of claudication after chemoradiation treatment of
      locally advanced squamous cell carcinoma of the vulva and vagina. Healing
      occurred after surgical revascularization. CONCLUSION: Conditions with impaired
      microvasculature, such as smoking and atherosclerotic disease, are associated
      with an increased incidence and severity of complications after radiation
      treatment. Patients undergoing pelvic radiation treatment should be counseled to
      modify their vascular risk factors. If this fails and patients develop
      significant radiation necrosis due to compromised arteriole flow,
      revascularization or stenting may offer important treatment options.

PMID- 17507082
TI  - The relevance of microbial allergens to the IgE antibody repertoire in atopic and
      nonatopic eczema.
AB  - BACKGROUND: A propensity to microbial skin infections has been reported in atopic
      ("high IgE") and nonatopic ("low IgE") forms of eczema. However, the relationship
      between antimicrobial IgE antibodies and nonatopic disease is unclear. OBJECTIVE:
      We examined the relevance of microbial allergens to the allergen-specific IgE
      antibody repertoire in patients with atopic dermatitis. METHODS: Patients with
      IgE levels of less than 150 IU/mL were stratified according to sensitivity (n =
      22) or no sensitivity (n = 27) to 11 common food allergens and aeroallergens. The
      prevalence and titers of antimicrobial IgE antibodies were compared with those of
      patients (n = 36) with increased total IgE levels (>150 IU/mL). Skin-derived
      serum chemokines were also analyzed. RESULTS: Patients with low IgE levels showed
      decreased disease severity, increased age of onset, a striking female
      predominance, and a distinct distribution of skin lesions. High titer IgE
      antibodies (sum of 8 bacterial and fungal allergens = 29.8 +/- 32.6 IU/mL) and
      multisensitization specific for microbial allergens was characteristic of
      patients with high IgE levels, with an overall 84% positivity; however,
      antimicrobial IgE antibodies comprised 3% or less of allergen-specific IgE
      antibodies. By contrast, antimicrobial IgE antibodies were detected in only 20%
      of patients with low IgE, and titers were negligible, irrespective of
      sensitization to common allergens. These patients were monosensitized, and
      exclusive microbial sensitivity was uncommon (10%). Patients with low IgE with no
      sensitivity to common allergens had lower levels of serum macrophage inflammatory
      protein 3alpha compared with their sensitized counterparts. CONCLUSION:
      Antimicrobial IgE antibodies are uncommon in patients with atopic dermatitis with
      low IgE levels. CLINICAL IMPLICATIONS: Hypersensitivity to microbial allergens is
      an unlikely trigger for eczematous eruptions in patients with low IgE levels.

PMID- 17507083
TI  - Exposure to dust mite allergen and endotoxin in early life and asthma and atopy
      in childhood.
AB  - BACKGROUND: There has been no longitudinal study of the relation between
      concurrent exposure to dust mite allergen and endotoxin in early life and asthma
      and atopy at school age. OBJECTIVES: To examine the relation between exposure to
      dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and
      atopy in high-risk children. METHODS: Birth cohort study of 440 children with
      parental history of atopy in the Boston metropolitan area. RESULTS: In
      multivariate analyses, early exposure to high levels of dust mite allergen (> or
      =10 microg/g) was associated with increased risks of asthma at age 7 years (odds
      ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% CI, 1.5
      16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3
      months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI,
      0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure
      in early life was associated with an increased risk of any wheeze between ages 1
      and 7 years that did not change significantly with time (hazard ratio for each
      quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43). CONCLUSION:
      Among children at risk of atopy, early exposure to high levels of dust mite
      allergen is associated with increased risks of asthma and late-onset wheeze. In
      these children, endotoxin exposure is associated with a reduced risk of atopy but
      an increased risk of wheeze. CLINICAL IMPLICATIONS: Early endotoxin exposure may
      be a protective factor against atopy but a risk factor for wheeze in high-risk
      children.

PMID- 17507084
TI  - Histamine downregulates monocyte CCL2 production through the histamine H4
      receptor.
AB  - BACKGROUND: The expression of the recently cloned histamine H(4) receptor (H(4)R)
      by leukocytes suggests a role in immunomodulation. OBJECTIVE: The expression and
      function of the H(4)R on human monocytes obtained from peripheral blood was
      investigated. METHODS: H(4)R expression was studied by using flow cytometry.
      Effects of H(4)R stimulation on Ca(2+) mobilization was determined
      fluorometrically, CCL2 production was determined by means of ELISA, intracellular
      CCL2 staining was measured with flow cytometry, and CCL2 mRNA was measured by
      using real-time quantitative LightCycler PCR. The relevance of CCL2 production
      was determined in chemotaxis transmigration assays. RESULTS: H(4)R protein was
      expressed by monocytes and upregulated by IFN-gamma. H(4)R agonists (clobenpropit
      and 4-methylhistamine) induce a Ca(2+) mobilization in monocytes, which could be
      blocked with the selective H(4)R antagonist JNJ7,777,120. Furthermore, H(4)R
      agonists downregulated CCL2 protein production. This effect could also be blocked
      by JNJ7,777,120. Supernatants of H(4)R agonist-stimulated monocytes attracted
      less monocytes in transmigration assays. The downregulation of CCL2 production
      was regulated at different levels. First, the synthesis of CCL2 mRNA was
      significantly decreased. Second, intracellular staining suggested an inhibition
      of CCL2 secretion after stimulation with H(4)R agonists. CONCLUSION: Human
      monocytes express the H(4)R, and its stimulation leads to a Ca(2+) influx and an
      inhibition of CCL2 production, resulting in a reduction of monocyte recruitment.
      CLINICAL IMPLICATIONS: The H(4)R could represent an important anti-inflammatory
      receptor on monocytes and could be an interesting target for drug development.

PMID- 17507085
TI  - Regulation of GM-CSF expression by the transcription factor c-Maf.
AB  - BACKGROUND: Inflammation is a key feature of asthma and allergic disease. The
      proinflammatory cytokines IL-4, IL-5, and IL-13 are clustered on chromosome 5q
      with GM-CSF in close proximity, and each of these cytokines has been implicated
      in the pathogenesis of inflammatory disease. Although the expression of IL-4, IL
      5, and IL-13 is coordinately regulated, the T(H)2-associated transcription factor
      c-Maf is thought to be involved only in the regulation of IL-4, the cytokine
      thought to be the main driver of T(H)2 differentiation. OBJECTIVE: We sought to
      determine whether c-Maf influenced the expression of proinflammatory cytokines
      other than IL-4 in the Jurkat human T-cell line. METHODS: RT-PCR, ELISA, and
      promoter-driven CAT assays were used to determine the effect of c-Maf
      overexpression on cytokine genes. A biotinylated oligo pulldown assay was used to
      demonstrate recruitment of c-Maf to the GM-CSF promoter. RESULTS: We found that
      in addition to induction of IL-4, c-Maf could upregulate GM-CSF expression at
      both mRNA and protein levels, and that c-Maf could strongly activate the
      promoters of GM-CSF and IL-4 but not IL-5. Recruitment of c-Maf to the -33 to -97
      bp region of the GM-CSF promoter was demonstrated. CONCLUSION: We propose a novel
      role for c-Maf in the transcriptional regulation of GM-CSF in human T cells.
      CLINICAL IMPLICATIONS: These data suggest that c-Maf may be a therapeutic target
      affecting both IL-4 and GM-CSF.

PMID- 17507087
TI  - The effect of a leucite-containing ceramic filler on the abrasive wear of dental
      composites.
AB  - OBJECTIVES: The aim of this study was to evaluate abrasive wear of a dental
      composite based on a leucite-containing (KAlSi2O2 ceramic filler, and to compare
      it with the wear of a composite based on commonly used aluminum barium silicate
      glass filler. METHODS: IPS Empress (Ivoclar-Vivadent) ingots were ball milled,
      passed through an 800 mesh (ASTM) sieve, and used as the leucite ceramic filler.
      Experimental composites were prepared by mixing the silane-treated fillers with
      the resin monomers. The resin consisted of 70 wt% Bis-GMA and 30 wt% TEGDMA
      containing camphorquinone and DMAEMA as the photoinitiator system. Glass-based
      composites were also prepared using silane-treated aluminum barium silicate glass
      fillers and the same resin system. TetricCeram, a commercially available dental
      composite, was used as control. Spherical specimens of the composites were then
      prepared and kept in water for 2 weeks to reach equilibrium with water. An
      abrasive wear test was performed using a device designed in our laboratory and
      weight loss of the specimens was measured as an abrasion parameter after each 50
      h. SEMs were taken from worn and fractured surfaces. Degree-of-conversion of the
      composites was measured using FTIR spectroscopy. Vickers surface microhardness,
      flexural strength, and flexural modulus of the composites were also measured. The
      data were analyzed and compared using ANOVA and Tukey HSD tests (significance
      level=0.05). RESULTS: The results showed that there were significant differences
      among the abrasive wear of the composites (p<0.05). The ranking from least to
      most was as: leucite-based composite<TetricCeram<glass-based composite. The
      higher wear resistance of leucite-based composite could be related to its higher
      surface hardness. SIGNIFICANCE: Using leucite-containing glass as an alternative
      for aluminum barium silicate glass fillers in dental composites generated a
      significant increase in the wear resistance of the resin composites which should
      be beneficial in the development of dental materials.

PMID- 17507088
TI  - Brief report: British adolescents' views about the rights of asylum-seeking
      children.
AB  - The present study examined 60 (30 early-to-middle adolescents and 30 late
      adolescents) British adolescents' understanding of the rights of asylum-seeker
      children. Participants completed semi-structured interviews designed to assess
      judgments and evaluations of hypothetical asylum-seeker children's nurturance and
      self-determination rights in conflict with the practices of authority. Findings
      indicated that participants were more likely to endorse asylum-seeker children's
      nurturance rights over their self-determination rights. Reasoning about both
      types of rights was multifaceted and focused on moral, social-conventional and
      psychological considerations. In addition, significant differences were found
      between males and females with regard to both endorsement and reasoning. The
      limitations of the study are discussed and future research is considered.

PMID- 17507086
TI  - Tocotrienols in health and disease: the other half of the natural vitamin E
      family.
AB  - Tocochromanols encompass a group of compounds with vitamin E activity essential
      for human nutrition. Structurally, natural vitamin E includes eight chemically
      distinct molecules: alpha-, beta-, gamma- and delta-tocopherol; and alpha-, beta
      , gamma- and delta-tocotrienol. Symptoms caused by alpha-tocopherol deficiency
      can be alleviated by tocotrienols. Thus, tocotrienols may be viewed as being
      members of the natural vitamin E family not only structurally but also
      functionally. Palm oil and rice bran oil represent two major nutritional sources
      of natural tocotrienol. Taken orally, tocotrienols are bioavailable to all vital
      organs. The tocotrienol forms of natural vitamin E possesses powerful
      hypocholesterolemic, anti-cancer and neuroprotective properties that are often
      not exhibited by tocopherols. Oral tocotrienol protects against stroke-associated
      brain damage in vivo. Disappointments with outcomes-based clinical studies
      testing the efficacy of alpha-tocopherol need to be handled with caution and
      prudence recognizing the untapped opportunities offered by the other forms of
      natural vitamin E. Although tocotrienols represent half of the natural vitamin E
      family, work on tocotrienols account for roughly 1% of the total literature on
      vitamin E. The current state of knowledge warrants strategic investment into
      investigating the lesser known forms of vitamin E.

PMID- 17507089
TI  - A biomimetic peptide fluorosurfactant polymer for endothelialization of ePTFE
      with limited platelet adhesion.
AB  - Endothelialization of expanded polytetrafluoroethylene (ePTFE) has the potential
      to improve long-term patency for small-diameter vascular grafts. Successful
      endothelialization requires ePTFE surface modification to permit cell attachment
      to this otherwise non-adhesive substrate. We report here on a peptide
      fluorosurfactant polymer (FSP) biomimetic construct that promotes endothelial
      cell (EC)-selective attachment, growth, shear stability, and function on ePTFE.
      The peptide FSP consists of a flexible poly(vinyl amine) backbone with EC
      selective peptide ligands for specific cell adhesion and pendant fluorocarbon
      branches for stable anchorage to underlying ePTFE. The EC-selective peptide
      (primary sequence: Cys-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys, CRRETAWAC) has
      demonstrated high binding affinity for the alpha(5)beta(1) integrin found on ECs.
      Here, we demonstrate low affinity of CRRETAWAC for platelets and platelet
      integrins, thus providing it with EC-selectivity. This EC-selectivity could
      potentially facilitate rapid in vivo endothelialization and healing without
      thrombosis for small-diameter ePTFE vascular grafts.

PMID- 17507090
TI  - Practical recombinant hybrid mussel bioadhesive fp-151.
AB  - Mussel adhesive proteins (MAPs) have received increased attention as potential
      environmentally friendly adhesives under aqueous conditions and in medicine.
      However, attempts to produce functional recombinant MAPs (mainly foot protein
      type 1, fp-1) by several expression systems have failed. Even though we
      previously reported a functional expression of recombinant foot protein type 5
      (fp-5) with significant adhesive ability in Escherichia coli, its practical use
      was limited by several problems such as low production yield, low purification
      yield, and high levels of post-purification insolubility. Here, to overcome these
      limitations, we designed and constructed the novel type of hybrid mussel
      bioadhesive fp-151, a fusion protein comprising six fp-1 decapeptide repeats at
      each fp-5 terminus. Using micro- and bulk-scale characterization and mammalian
      cell-adhesion analyses, we demonstrate that fp-151 has the potential to be a
      practical bioadhesive with strong adhesive ability, a simple purification process
      ( approximately 1g-purified protein per 1l-pilot-scale fed-batch bioreactor
      culture), proper manipulation properties ( approximately 330g/l solubility), and
      high biocompatibility.

PMID- 17507091
TI  - Idiopathic cytopenia of undetermined significance (ICUS) versus low risk MDS: the
      diagnostic interface.
AB  - It may sometimes be difficult to diagnose low risk MDS in patients with mild
      cytopenia. We report on 10 patients with mild to marked, unexplained cytopenia
      without definitive signs of a myeloid neoplasm. In two patients, a karyotype
      abnormality (trisomy 14; monosomy 7) was detected in a small subset of bone
      marrow cells. Progression to overt MDS was seen in two patients including the one
      with monosomy 7. In the remaining cases, no MDS developed in a follow-up of at
      least 6 months. The phrase "idiopathic cytopenia of undetermined significance
      (ICUS)", as also suggested by Mufti and co-workers, is proposed and long term
      follow-up is recommended to assess the evolution.

PMID- 17507092
TI  - Clustering in the incidence of myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) are a group of malignancies with poor
      prognosis and obscure etiology. To better understand the distribution of MDS in
      the population and help generate etiologic hypotheses, we assessed potential
      clustering in the incidence of MDS in the state of Connecticut using population
      based cancer registry data that recently became available. A significant spatial
      clustering was identified. The most likely area with a high incidence of MDS
      included 46 census tracts near the west border of Connecticut, and the ratio of
      observed/expected cases was 2.84. The P value associated with this cluster was
      0.0001. Although no temporal clustering was indicated, a space-time analysis
      identified a cluster in the central south of Connecticut from March 2002 through
      August 2003 (P=0.008). This is the first analysis of potential clustering in the
      incidence of MDS using population-based data. If the intriguing finding on
      spatial clustering is supported by future studies with larger sample sizes and/or
      in other geographic areas, it would be extremely interesting to explore the
      "causes" of clustering, which may help shed light on the etiology of MDS.

PMID- 17507093
TI  - Analysis of two theta-replicating plasmids of Streptococcus thermophilus.
AB  - We report the characterization of two new theta-replicating plasmids of
      Streptococcus thermophilus (pSMQ-312b and pSMQ-316) as well as the further
      analysis of pSMQ-308. The nucleotide sequences of pSMQ-312b and pSMQ-316 were
      determined and both contained 6710 bp. In fact, the two sequences were identical,
      despite that the plasmids were isolated from two different S. thermophilus
      strains as demonstrated by pulsed-field gel electrophoresis. Comparative analyses
      indicated that the two plasmids were highly related to the previously
      characterized S. thermophilus plasmid pSMQ-308 (8144 bp). Plasmid stability tests
      showed that pSMQ-312b/316 was more stable in LM17 medium while pSMQ-308 was the
      most stable in milk. The presence of the plasmids did not modify the
      acidification profile of the S. thermophilus strains during growth in milk and
      under time-temperature conditions mimicking an industrial process. These theta
      replicating plasmids are unique genetic material for the construction of stable
      cloning vectors for industrially relevant strains of S. thermophilus.

PMID- 17507094
TI  - Sensitivity of TLR4- and -7-induced NF kappa B1 p105-TPL2-ERK pathway to TNF
      receptor-associated-factor-6 revealed by RNAi in mouse macrophages.
AB  - Tumor necrosis factor (TNF)-receptor-associated-factor-6 (TRAF6) is an adaptor
      protein involved in Toll-like receptor (TLR) signaling. Recent studies using
      macrophages from TRAF6 knockout mice have revealed that TRAF6 is required for
      TLR7 signaling. However, an essential role of TRAF6 in TLR4 signaling and
      cytokine production is slightly controversial. Using an RNAi approach to reduce
      the cellular levels of TRAF6, we tested the role of this adaptor protein on the
      sensitivity of the various components of the ERK pathway mediated by TLR4 and -7
      in Raw264.7, a mouse macrophage cell line. ERK activation in macrophages by TLR4
      and -7 is mediated via a MAP3K, called TPL2/COT, which under unstimulated
      conditions is associated with NF kappa B1 p105, a member of the I kappa B family
      of proteins. Upon stimulation with TLR ligands, p105 is phosphorylated by I kappa
      B kinase (IKK) complex and partially degraded, which releases TPL2. The free TPL2
      is active and stimulates the ERK pathway via MEK1/2. The free TPL2, however, is
      also unstable and is targeted for degradation. We demonstrate here that reduced
      level of TRAF6 ( approximately 80% decrease) in macrophages does not
      significantly affect any of the components of the TLR4-stimulated ERK pathway,
      including p105 phosphorylation, TPL2 degradation and ERK1/2 phosphorylation.
      Surprisingly, however, TLR4-induced JNK1/2 phosphorylation is significantly
      blocked by TRAF6 knockdown, suggesting that ERK and JNK pathways are
      differentially sensitive to TRAF6 levels. Furthermore, although TLR4-mediated IKK
      induced p105 phosphorylation is not sensitive to TRAF6 knockdown, I kappa B alpha
      phosphorylation (also, IKK-induced) is significantly blocked, suggesting that
      TLR4 activation results in a TRAF6-sensitive and -insensitive IKK activation in
      macrophages. In contrast to TLR4 signaling, TLR7 activation of ERK, JNK pathways
      and phosphorylation of p105 and I kappa B alpha are completely inhibited in TRAF6
      knockdown cells. Compared to the signaling data, while TLR4-induced TNFalpha mRNA
      expression is not significantly inhibited by TRAF6 knockdown, TLR7-induced
      TNFalpha mRNA is significantly blocked. In contrast, both TLR4- and TLR7-induced
      IL6 mRNA are significantly blocked by TRAF6 knockdown. These results suggest that
      while TRAF6 is absolutely essential for TLR7 activation of ERK, JNK and NF kappa
      B pathways, TLR4-induced ERK, JNK pathways and IKK-mediated phosphorylation of I
      kappa B family members as well as cytokine expression are differentially
      sensitive to the cellular levels of TRAF6. These results have important
      implications in terms of therapeutic targeting of TRAF6 complexes in diseases
      where TLR4 and -7 are involved.

PMID- 17507095
TI  - Targeting of humanized antibody D93 to sites of angiogenesis and tumor growth by
      binding to multiple epitopes on denatured collagens.
AB  - A humanized, affinity-matured IgG1 antibody, called D93, and its parental murine
      IgM HUI77 have been shown to specifically bind denatured collagens and thereby
      inhibit angiogenesis and tumor growth in various animal models. In this study, we
      have identified epitopes for both HUI77 and D93 on human collagen type IV.
      Several tryptic D93-binding peptides were identified by Western blot analysis and
      protein sequencing. Epitopes for D93 were ultimately identified by screening a
      synthetic 16-mer peptide array spanning immunoreactive tryptic peptides. D93
      reacted with a peptide corresponding to alpha1(IV) P(1337)-Y(1352) that could
      inhibit binding of both D93 and HUI77 to denatured collagen IV in a concentration
      dependent manner. A 9-mer peptide corresponding to alpha1(IV) G(1344)-Y(1352)
      showed maximum inhibition of D93 and HUI77 antibody binding to denatured collagen
      IV, and was critically dependent on the presence of hydroxyproline. D93 bound
      with similar affinity to denatured collagen IV and synthetic peptides with a K(D)
      of 1-10 microM for monovalent and of 30-63 nM for bivalent binding. Potential
      epitopes for D93 are highly repeated in multiple collagen types of diverse
      vertebrate species explaining reactivity of D93 with denatured collagens types I
      V from chicken to man. Our data suggest that D93 inhibits angiogenesis and tumor
      growth by blockade of cryptic bioactive signals on proteolyzed collagens with
      importance for growth of tumors and new blood vessels.

PMID- 17507096
TI  - Three-dimensional imaging of the foveal photoreceptor layer in central serous
      chorioretinopathy using high-speed optical coherence tomography.
AB  - OBJECTIVE: To describe the 3-dimensional (3-D) imaging of the pathologic changes
      in the foveal photoreceptor layer in eyes with central serous chorioretinopathy
      (CSC) using high-speed optical coherence tomography (OCT). DESIGN: Prospective
      observational case series. PARTICIPANTS: Twenty-seven eyes of 27 consecutive
      patients with various stages of CSC. METHODS: A prototype high-speed OCT system
      was fabricated for patient examinations based on Fourier domain OCT. The system
      had a sensitivity of 98 dB, a tissue axial resolution of 4.3 mum, and an
      acquisition rate of approximately 18700 axial scans per second. Three-dimensional
      imaging was performed based on a raster-scan protocol. MAIN OUTCOME MEASURES:
      Anatomic features of CSC distinguished by 3-D OCT. RESULTS: A line corresponding
      to backreflection from the external limiting membrane (ELM) was visible in images
      from eyes with all stages of CSC, including 6 in the acute, 5 in the chronic, and
      9 in the recurrent phase of retinal detachment and 11 examined in the quiescent
      phase (including 4 reexamined after reattachment). Backreflection from the
      photoreceptor inner and outer segment junction (IS/OS) was missing before but
      present after reattachment. The ELM line bordered the photoreceptor nuclear and
      inner segment layers, clearly showing that CSC primarily alters the outer segment
      (OS) layer. Punctate areas of intense reflectivity were observed more frequently
      in the OS layer of detached retinas in cases of chronic or recurrent versus acute
      CSC (P<0.05, chi-square test). Of 11 eyes with reattached macula, 3 eyes with
      large defects in the subfoveal IS/OS had poor visual acuity (VA), and 8 eyes with
      small or no defects had good VA (P<0.05 and P<0.001, chi-square test). Decreases
      in foveal full and outer thickness were associated with VA loss (P<0.05 and
      P<0.001, Spearman rank correlation test). CONCLUSIONS: Three-dimensional OCT
      imaging delineates the microstructural changes that occur within the
      photoreceptor layers and demonstrates the spatial relationship between the
      laterally spreading or scattering microstructures and the fovea in eyes with CSC.
      Visualization of the 3-D relationship between the ELM and each photoreceptor
      layer before and after macular reattachment facilitates understanding of anatomic
      and vision changes that result from CSC.

PMID- 17507097
TI  - Agreement among 3 methods to measure corneal thickness: ultrasound pachymetry,
      Orbscan II, and Visante anterior segment optical coherence tomography.
AB  - PURPOSE: To assess the agreement of central and paracentral corneal thickness
      measurements between ultrasound pachymetry (USP), Orbscan II, and Visante
      anterior segment optical coherence tomography (ASOCT). DESIGN: Observational
      cross-sectional study. PARTICIPANTS: Seventy eyes of 70 subjects. METHODS: Each
      subject underwent Orbscan II (using an acoustic equivalent correction factor of
      0.89), ASOCT, and USP examination. Bland-Altman plots were used to evaluate
      agreement between instruments. MAIN OUTCOME MEASURES: Central and paracentral
      corneal thickness measurements by the 3 methods and agreement, as evaluated by
      95% limits of agreement (LOA). RESULTS: The mean measurements of average central
      corneal thickness by USP, Orbscan II, and ASOCT were 553.5+/-30.26 microm,
      553.22+/-25.47 microm, and 538.79+/-26.22 microm, respectively. There was high
      correlation between instruments: USP with ASOCT (r = 0.936, P<0.001), USP with
      Orbscan II (r = 0.900, P<0.001) for central corneal thickness measurements, and
      Orbscan II with ASOCT for average paracentral 2- to 5-mm measurements (r = 0.947,
      P<0.001). The mean differences (and upper/lower LOA) for central corneal
      thickness measurements were 0.31+/-13.34 microm (26.44/-25.83) between USP and
      Orbscan II, 14.74+/-10.84 microm (36.0/-6.51) between USP and ASOCT, and 14.44+/
      9.14 microm (32.36/-3.48) between Orbscan II and ASOCT. The average mean
      difference (and upper/lower LOA) between Orbscan II and ASOCT for paracentral 2-
      to 5-mm corneal thickness measurements was 10.35+/-8.67 microm (27.35/-6.65).
      CONCLUSION: Anterior segment optical coherence tomography underestimated corneal
      thickness compared with that measured with USP. Anterior segment optical
      coherence tomography had better agreement with the gold standard USP, as compared
      with Orbscan II. However, important discrepancies among instruments exist.
      Clinicians should be aware that corneal thickness measurements are influenced by
      the method of measurement and that, although highly correlated, these instruments
      should not be used interchangeably for the assessment of corneal thickness.

PMID- 17507098
TI  - Morphometry of corneal endothelium in patients with corneal guttata.
AB  - OBJECTIVE: To study the morphology of the corneal endothelium in patients
      diagnosed with corneal guttata using an image processing algorithm based on a
      contour detection method. DESIGN: Retrospective observational case series.
      PARTICIPANTS: Twenty-four subjects with known corneal guttata. METHODS: Two
      hundred eight images of corneal endothelium, captured with a noncontact specular
      microscope were analyzed using the Contour method, which demonstrates endothelial
      cell density (ECD), coefficient of variation of cell area, percentage of 4- to 8
      sided cells as well as the number, area, and coefficient of variation of corneal
      guttata. MAIN OUTCOME MEASURES: The number, surface area, and coefficient of
      variation of corneal guttata. RESULTS: Corneal position had no significant effect
      on ECD or on the percentage of endothelial cells with 4, 5, 7, or 8 sides.
      However, the coefficient of variation of images taken from the central cornea was
      significantly larger than those taken at the 2- and 6-o'clock positions. In
      addition, the percentage of hexagonal cells was significantly lower in pictures
      of the central position compared to those located in the upper paracentral
      position. The numbers and surface areas of guttata were significantly larger in
      pictures of the central compared to some paracentral positions. Subjects who had
      previously undergone cataract surgery with intraocular lens (IOL) implantation
      did not show different areas of corneal guttata, but exhibited a significantly
      lower cell density (1825+/-582) compared with unoperated patients (2400+/
      457/mm2). Analogously, the only significant change observed in paired comparisons
      between the operated eye of patients with unilateral cataract extraction with IOL
      implantation and their unoperated fellow eye was a lower cell density obtained in
      operated eyes. Compared with normal subjects, subjects with corneal guttata were
      shown to have a significantly lower ECD, a lower proportion of hexagonal cells,
      and a higher coefficient of variation of cell area in the central cornea.
      CONCLUSION: This study supports the finding that corneal guttata mainly affect
      the central corneal area. A future prospective study using the described Contour
      detection method would be helpful to evaluate more accurately the risks
      associated with the evolution of corneal guttata into Fuchs' dystrophy.

PMID- 17507099
TI  - Risk factors for the incidence and persistence of suicide-related outcomes: a 10
      year follow-up study using the National Comorbidity Surveys.
AB  - BACKGROUND: We report prospective associations of baseline risk factors with the
      first onset and persistence of suicide-related outcomes (SROs; ideation, plans,
      gestures, and attempts) over a 10-year interval among respondents who
      participated in both the 1990-02 National Comorbidity Survey (NCS) and the 2000
      02 National Comorbidity Survey follow-up (NCS-2). METHODS: A total of 5001 NCS
      respondents were re-interviewed (87.6% of baseline sample) in the NCS-2. Three
      sets of baseline (NCS) risk factors were considered as predictors of the first
      onset and persistence of SROs: socio-demographics, lifetime DSM-III-R disorders,
      and SROs. RESULTS: New onsets included 6.2% suicide ideation, 2.3% plan, 0.7%
      gesture, and 0.9% attempts. More than one-third of respondents with a baseline
      history of suicide ideation continued to have suicide ideation at some time over
      the intervening decade. Persistence was lower for other SROs. The strongest
      predictors of later SROs were baseline SROs. Prospective associations of baseline
      mental disorders with later SROs were largely limited to the onset and
      persistence of ideation. LIMITATIONS: Although data were gathered prospectively,
      they were based on retrospective reports at both baseline and follow-up.
      CONCLUSIONS: Baseline history of SROs explained much of the association of mental
      disorders with later SROs. It is important clinically to note that many of the
      risk factors known to predict onset of SROs also predict persistence of SROs.

PMID- 17507100
TI  - Neuropsychological frontal impairments and negative symptoms in schizophrenia.
AB  - Negative symptoms have been associated with frontal lobe dysfunction in
      schizophrenia. However, neuropsychological studies that evaluated the correlation
      between performance in tests sensitive to the dorsolateral prefrontal cortex
      (DLPFC) and negative symptoms have shown inconsistent results. Growing evidence
      has appeared that not only the DLPFC but other prefrontal regions could be
      involved in schizophrenia. We evaluated schizophrenic patients and healthy
      controls using three "frontal tests": the Wisconsin Card Sorting Test (WCST), the
      Iowa Gambling Task (GT) and a Theory of Mind test (Faux Pas), and studied the
      relationship between performance in these tests and negative symptomatology.
      Schizophrenic patients had worse performance than normal controls on the WCST, GT
      and Faux Pas test. The severity of the negative symptoms showed a moderate to
      high correlation with performance in the Faux Pas test. Our findings support the
      idea that different prefrontal regions could be affected in people with
      schizophrenia and that the damage to each of these regions could be, at least in
      part, independent of the damage to the others. Some negative symptoms could be
      associated with frontal medial cortex dysfunction.

PMID- 17507101
TI  - IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine
      mesenchymal stem cells.
AB  - Murine mesenchymal stem cells (MSC) have the ability to inhibit allogeneic immune
      responses. Two different mechanisms, either cell contact-dependent or
      independent, have been proposed to account for this immunosuppression. The focus
      of this study was to elucidate the involvement of soluble suppressive factors
      secreted by murine MSC in an inflammatory setting, and their role in MSC
      immunomodulation. In a non-inflammatory environment, bone marrow derived murine
      MSC constitutively expressed low levels of COX-2, PGE-2, TGF-beta1 and HGF, but
      not IL-10, PD-1, PD-L1 or PD-L2. These MSC were able to significantly reduce
      alloantigen driven proliferation in mixed lymphocyte reactions as well as mitogen
      driven proliferation. The pro-inflammatory cytokines IFN-gamma and TNF-alpha did
      not ablate MSC mediated immunosuppression. MSC expression of PGE-2, IDO and PD-L1
      was differentially regulated by these cytokines. COX-2 and PGE-2 expression by
      MSC were upregulated by both IFN-gamma and TNF-alpha, and using a biochemical
      inhibitor this was shown to have an essential, non-redundant role in modulating
      alloantigen-driven proliferation. However, the surface expression of PD-L1 was
      induced by IFN-gamma but not TNF-alpha and similarly functional IDO expression
      was only induced by IFN-gamma stimulation. Blocking studies using neutralising
      antibodies and biochemical antagonists revealed that while PD-L1 induction was
      not essential, IDO expression was a prerequisite for IFN-gamma mediated MSC
      immunomodulation. These data demonstrate that murine MSC expression of
      immunomodulatory factors dramatically changes in a pro-inflammatory environment
      and that IFN-gamma in particular has an important role in regulating MSC
      immunomodulatory factor expression.

PMID- 17507102
TI  - GABAergic inactivation of basolateral amygdala alters behavioral processes other
      than primary reward of ventral tegmental self-stimulation.
AB  - Although recent work on amygdalar function has concentrated on a role in fear and
      anxiety, a possible role in reward processes continues to be considered. This
      function may occur via anatomical connections between the basolateral amygdala
      (BLA) and the mesoaccumbens dopamine (DA) system (i.e., ventral tegmental area
      [VTA] to nucleus accumbens septi [NAS]), particularly at the level of the NAS.
      The current experiments investigated a possible role of the BLA in the reward of
      intracranial self-stimulation (ICSS) of the VTA. Rats were trained in either an
      autotitration ICSS task or a rate-frequency ICSS task. We examined the effect of
      intra-BLA injections of muscimol, a GABA(A) agonist which inhibits the firing of
      most neurons, on VTA ICSS in both behavioral procedures. The injections produced
      a pattern of behavioral change which, across the two tasks, was more consistent
      with a change in behavioral processes other than primary reward. Possible
      processes include cost/benefit analysis and incentive motivation.

PMID- 17507103
TI  - Effect of selenate on growth and photosynthesis of Chlamydomonas reinhardtii.
AB  - Algal communities play a crucial role in aquatic food webs by facilitating the
      transfer of dissolved inorganic selenium (both an essential trace element and a
      toxic compound for a wide variety of organisms) to higher trophic levels. The
      dominant inorganic chemical species of selenium in freshwaters are selenite
      (SeO(3)(2-)) and selenate (SeO(4)(2-)). At environmental concentrations, selenite
      is not likely to have direct toxic effects on phytoplankton growth [Morlon, H.,
      Fortin, C., Floriani, M., Adam, C., Garnier-Laplace, J., Boudou, A., 2005a.
      Toxicity of selenite in the unicellular green alga Chlamydomonas reinharditii:
      comparison between effects at the population and sub-cellular level. Aquat.
      Toxicol. 73(1), 65-78]. The effects of selenate, on the other hand, are poorly
      documented. We studied the effects of selenate on Chlamydomonas reinhardtii
      growth (a common parameter in phytotoxicity tests). Growth inhibition (96-h
      IC(50)) was observed at 4.5+/-0.2 microM selenate (p<0.001), an effective
      concentration which is low compared to environmental concentrations. Growth
      inhibition at high selenium concentrations may result from impaired
      photosynthesis. This is why we also studied the effects of selenate on the
      photosynthetic process (not previously assessed in this species to our knowledge)
      as well as selenate's effects on cell ultrastructure. The observed
      ultrastructural damage (chloroplast alterations, loss of appressed domains)
      confirmed that chloroplasts are important targets in the mechanism of selenium
      toxicity. Furthermore, the inhibition of photosynthetic electron transport
      evaluated by chlorophyll fluorescence induction confirmed this hypothesis and
      demonstrated that selenate disrupts the photosynthetic electron chain. Compared
      to the classical 'growth inhibition' parameter used in phytotoxicity tests, cell
      diameter and operational photosynthetic yield were more sensitive and may be
      convenient tools for selenate toxicity assessment in non-target plants.

PMID- 17507104
TI  - Differential regulation of Ku gene expression in etiolated mung bean hypocotyls
      by auxins.
AB  - Plant Ku genes were identified very recently in Arabidopsis thaliana, and their
      roles in repair of double-stranded break DNA and maintenance of telomere
      integrity were scrutinized. In this study, the cDNAs encoding Ku70 (VrKu70) and
      Ku80 (VrKu80) were isolated from mung bean (Vigna radiata L.) hypocotyls. Both
      genes were expressed widely among different tissues of mung bean with the highest
      levels in hypocotyls and leaves. The VrKu gene expression was stimulated by
      exogenous auxins in a concentration- and time-dependent manner. The stimulation
      could be abolished by auxin transport inhibitors, N-(1-naphthyl) phthalamic acid
      and 2,3,5-triiodobenzoic acid implicating that exogenous auxins triggered the
      effects following their uptake by the cells. Further analysis using specific
      inhibitors of auxin signaling showed that the stimulation of VrKu expression by
      2,4-dichlorophenoxyacetic acid (2,4-D) was suppressed by intracellular Ca(2+)
      chelators, calmodulin antagonists, and calcium/calmodulin dependent protein
      kinase inhibitors, suggesting the involvement of calmodulin in the signaling
      pathway. On the other hand, exogenous indole-3-acetic acid (IAA) and alpha
      naphthalene acetic acid (NAA) stimulated VrKu expression through the mitogen
      activated protein kinase/extracellular signal-regulated kinase pathway.
      Altogether, it is thus proposed that 2,4-D and IAA (or NAA) regulate the
      expression of VrKu through two distinct pathways.

PMID- 17507105
TI  - Comparison of sarpogrelate and ticlopidine in bare metal coronary stent
      implantation.
AB  - BACKGROUND: The efficacy and safety of sarpogrelate, a selective 5
      hydroxytryptamine receptor subtype 2A antagonist, have not yet been established
      in bare metal coronary stenting. Accordingly, we sought to clarify whether
      treatment with sarpogrelate is clinically useful in bare metal coronary stenting.
      METHODS: A total of 450 patients who underwent successfully planned or unplanned
      bare metal coronary stenting were randomly divided into the following 2 groups:
      the sarpogrelate (300 mg/day) plus aspirin (100 mg/day) group (group S, n=225)
      and the ticlopidine (200 mg/day) plus aspirin (100 mg/day) group (group T,
      n=225). Either sarpogrelate or ticlopidine was administered for at least 4 weeks
      after the procedure. Follow-up coronary arteriography was performed at 6 months
      after the procedure. The primary endpoints were the incidence of adverse drug
      reactions requiring a withdrawal of treatment and the rate of binary restenosis.
      The secondary endpoint was the incidence of stent thrombosis. RESULTS: The
      incidence of adverse drug reactions requiring a withdrawal of treatment was
      significantly lower in group S than in group T (0.44% vs 8%, p=0.002). The rate
      of binary restenosis did not differ significantly between groups S and T (16.9%
      vs 18.2%). In addition, the incidence of subacute stent thrombosis did not differ
      between groups S and T (0.44% vs 0.44%). CONCLUSIONS: The incidence of adverse
      drug reactions requiring a withdrawal of treatment was significantly lower with
      sarpogrelate use than with ticlopidine use. The rate of binary restenosis and the
      incidence of subacute stent thrombosis did not differ between both drug groups.

PMID- 17507106
TI  - A model (BSurvE) for estimating the prevalence of bovine spongiform
      encephalopathy in a national herd.
AB  - We developed the BSurvE spreadsheet model to estimate the true prevalence of
      bovine spongiform encephalopathy (BSE) in a national cattle population, and
      evaluate national BSE surveillance programs. BSurvE uses BSE surveillance data
      and demographic information about the national cattle population. The proportion
      of each cohort infected with BSE is found by equating the observed number of
      infected animals with the number expected, following a series of probability
      calculations and assuming a binomial distribution for the number of infected
      animals detected in each surveillance stream. BSurvE has been used in a series of
      international workshops, where analysis of national datasets demonstrated
      patterns of cohort infection that were consistent with infection-control
      activities within the country. The results also reflected the timing of known
      events that were high-risk for introduction of the infectious agent.

PMID- 17507107
TI  - Preventive strategies and risk factors for milk fever in Danish dairy herds: a
      questionnaire survey.
AB  - Milk fever is a commonly recognized production disease in dairy cows around
      parturition. The aim of this questionnaire survey was therefore to investigate
      milk fever preventive strategies used in Danish dairy herds during 1998, to
      explore the reasons for choosing a specific strategy, and finally to evaluate
      possible risk factors for milk fever occurrences. A random sample of 230 milk
      producers (MP) was drawn from the Danish Cattle Database. A telephone interview
      (TI) was used to collect data. A sub-sample of 25% MPs was chosen by systematic
      random sampling and interviewed a second time (TI(2)). Descriptive analysis of
      all answers was performed. The agreement between TI(1) and TI(2) was evaluated
      using Cohen's kappa coefficient and the overall intra-MP agreement. Risk factors
      (such as housing systems or use of milk fever preventive strategies) for
      differences in milk fever incidences between herds were evaluated using logistic
      regression. This investigation revealed that Danish MPs focused on a few well
      described milk fever preventive principles and other management methods, such as
      reduced milking and management of body condition. There was no significant
      difference in risk of developing milk fever using different prevention strategies
      (p=0.80). Furthermore, the logistic regression did not indicate an association
      between reported milk fever cases and the assessments of this as a problem or not
      (p=0.09). Tie stalls increased the risk of milk fever compared to loose housing
      systems (p=0.019). There was a significant difference in risk of milk fever
      between parities. The overall milk fever incidence risk was 3.0%.

PMID- 17507108
TI  - O-CAS, a fast and universal method for siderophore detection.
AB  - In this work, the popular CAS assay for siderophore detection, based on the
      utilization of chrome azurol S, was redesigned and optimized to produce a new,
      fast, non-toxic, and easy method to determine a wide variety of microorganisms
      capable of siderophore production on a solid medium. Furthermore, this specific
      bioassay allows for the identification of more than one single siderophore
      producing microorganism at the same time, using an overlay technique in which a
      modified CAS medium is cast upon culture agar plates (thus its name "O-CAS", for
      overlaid CAS). Detection was optimized through adjustments to the medium's
      composition and a quantifying strategy. Specificity of the bioassay was tested on
      microorganisms known for siderophore production. As a result, a total of 48
      microorganisms were isolated from three different types of samples (fresh water,
      salt water, and alkaline soil), of which 36 were determined as siderophore
      producers. The compounds identified through this method belonged to both
      hydroxamate and catechol-types, previously reported to cause color change of the
      CAS medium from blue to orange and purple, respectively. Some isolated
      microorganisms, however, caused a color change that differed from previous
      descriptions.

PMID- 17507109
TI  - Training for older adults.
AB  - Aging is associated with a reduction in physical fitness, with loss of muscular
      force and endurance. Physical activity has been demonstrated to provide
      substantial health benefits and to maintain functional independence and improve
      quality of life in older adults. Resistance training has a significant effect on
      muscle mass and force whereas endurance training increases oxygen transport and
      consumption capacities. This article presents training methods used in the
      literature and their associated effects in order to adapt training protocols to
      older populations. To maximise benefits from adoption of a program to which the
      patient can adhere for long time, it is important to tailor the exercise
      prescription to the individual.

PMID- 17507110
TI  - Critical flicker frequency: it is time to break down barriers surrounding minimal
      hepatic encephalopathy.

PMID- 17507111
TI  - Injectable matrices and scaffolds for drug delivery in tissue engineering.
AB  - Injectable matrices and depots have been the subject of much research in the
      field of drug delivery. The classical tissue engineering paradigm includes a
      matrix or scaffold to facilitate tissue growth and provide structural support,
      cells, and the delivery of bioactive molecules. As both tissue engineering and
      drug delivery techniques benefit from the use of injectable materials due to the
      minimal invasiveness of an injection, significant crossover should be observed
      between injectable materials in both fields. This review aims to outline
      injectable materials and processing techniques used in both tissue engineering
      and drug delivery and to describe methods by which current injectable materials
      in the field of drug delivery can be adapted for use as injectable scaffolds for
      tissue engineering.

PMID- 17507112
TI  - Protein subcellular relocalization: a new perspective on the origin of novel
      genes.
AB  - Gene duplication is considered to be the most important evolutionary process for
      generating novel genes. However, the mechanisms involved in the evolution of such
      genetic innovations remain unclear. There is compelling evidence to suggest that
      changing the subcellular location of a protein can also alter its function, and
      that diversity in subcellular targeting within gene families is common. Here, we
      introduce the idea that protein subcellular relocalization might be an important
      evolutionary mechanism for the origins of new genes.

PMID- 17507113
TI  - Theory of active antidepressants: a nonsynaptic approach to the treatment of
      depression.
AB  - Although depression is one of the major neuropsychiatric disorders, the success
      rate of medication for any drug is about 60%, which means that approximately 40%
      of the patients does not respond to the initial treatment. The major aim of this
      review is to provide a possible explanation for the relative inefficacy of
      currently used antidepressants and to propose a novel mechanism of action, which
      might improve the success rate of clinical treatment. According to the monoamine
      theory the most important neurochemical process in depression is the impairment
      of monoaminergic neurotransmission and the concomitant decrease of extracellular
      concentration of noradrenaline and/or serotonin. Since the vast majority of
      monoaminergic varicosities makes no synaptic contact but is able to release
      transmitters directly into the extrasynaptic space, the monoaminergic
      neurotransmission is predominantly nonsynaptic in nature. Depression can be
      regarded, therefore, as a disease, which is developed (at least in part) on the
      basis of the impairment of nonsynaptic interactions and the effective treatment
      has to improve this non-conventional communication in the nervous system. The
      currently used antidepressants (reuptake inhibitors, negative feedback
      inhibitors, monoamino oxidase inhibitors) can increase the monoamine levels in
      the extracellular space only if the monoaminergic cells are electrically active
      and without an action potential-induced vesicular exocytosis these compounds are
      ineffective. It is proposed that a selective and moderate induction of the
      carrier-mediated release of NA and 5-HT might be a better therapeutic approach to
      the treatment of depression, since this new class of antidepressants, the so
      called 'active antidepressants' have a mechanism of action, which is independent
      from the electrical activity of monoaminergic cells, therefore the extrasynaptic
      concentration of monoamines and thereby the nonsynaptic communication can be
      enhanced more efficiently.

PMID- 17507114
TI  - The length of hippocampal cholinergic fibers is reduced in the aging brain.
AB  - Cholinergic deficits occur in the aged hippocampus and they are significant in
      Alzheimer's disease. Using stereological and biochemical approaches, we
      characterized the cholinergic septohippocampal pathway in old (24 months) and
      young adult (3 months) rats. The total length of choline acetyltransferase (ChAT)
      positive fibers in the dorsal hippocampus was significantly decreased by 32% with
      aging (F((1,9))=20.94, p=0.0014), along with the levels of synaptophysin, a
      presynaptic marker. No significant changes were detected in ChAT activity or in
      the amounts of ChAT protein, nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF), tropomyosin related kinase receptor (Trk) A, TrkB, or
      p75 neurotrophin receptor (p75(NTR)) in the aged dorsal hippocampus. The number
      and size of ChAT-positive neurons and the levels of ChAT activity, NGF and BDNF
      were not statistically different in the septum of aged and young adult rats. This
      study suggests that substantial synaptic loss and cholinergic axonal degeneration
      occurs during aging and reinforces the importance of therapies that can protect
      axons and promote their growth in order to restore cholinergic neurotransmission.

PMID- 17507115
TI  - Synthesis, structure and biological activity of pseudopeptidic macrolides based
      on an amino alcohol.
AB  - A series of new pseudopeptidic macrolides 2a-f based on an amino alcohol were
      synthesized and evaluated for in vitro antibacterial and antifungal activities.
      The structure-activity relationships of these compounds were studied and the
      results showed that compounds 2a and 2d exhibited moderate antibacterial activity
      against Staphylococcus aureus, Bacillus subtilis and Escherichia coli, whereas
      compound 2e showed potent antifungal activity against all the fungal species
      tested, showing a promising broad-spectrum antifungal activity. All the compounds
      have been studied in vitro for the hemolytic activity as a measure of their
      cytotoxicity, showing that these compounds have low lytic properties.

PMID- 17507116
TI  - Pathophysiology of cancer cachexia: much more than host-tumour interaction?
AB  - Cancer cachexia is a syndrome of progressive nutritional depletion which causes
      significant morbidity and mortality in cancer patients. One of the main
      pathogenetic mechanisms underlying cancer cachexia is a complex interaction
      between the host and the tumour. Tumour cells interact with host cells within the
      tumour mass resulting in the production of catabolic mediators which degrade host
      tissue. In addition, the host may mount an aberrant metabolic response to the
      tumour. However, in recent years, it has also been understood that patient
      factors, including age and levels of physical activity, and the specific
      mechanics of protein metabolism in cancer patients may also have a significant
      impact. In this review article, we not only summarise previous knowledge
      surrounding host-tumour interaction, but we also discuss these broader concepts
      in the pathogenesis of cancer cachexia. Clinicians should consider such concepts
      in the design of an effective multimodal therapy for cachexia.

PMID- 17507117
TI  - Development of intestinal bifidobacteria and lactobacilli in breast-fed neonates.
AB  - BACKGROUND & AIMS: Neonates are subject to numerous factors that affect normal
      intestinal colonization. This study was to quantify bifidobacteria and
      lactobacilli in the faeces of breast-fed neonates using quantitative real-time
      PCR assay, and to investigate the effects of different delivery on the
      development of bifidobacteria or lactobacilli. METHODS: The faecal bifidobacteria
      and lactobacilli of 40 healthy breast-fed neonates were studied prospectively.
      Twenty infants were vaginally delivered (VD), and 20 by caesarean delivery (CD)
      with prophylactically 4 g intravenous cefradine administered to their mothers
      three times. The faecal bifidobacteria and lactobacilli of neonates were
      consecutively quantified by SYBR Green I-based real-time PCR assay in the first 7
      days after birth. RESULTS: The mean levels of bifidobacteria increased from 5.1
      to 9.3 in the VD group vs from less than 4.6 to 8.7 in the CD group. The
      bifidobacteria colonization levels in six samples in the CD group were lower than
      the limit of detection on day 2. The mean levels of bifidobacteria in the VD
      group were significantly higher than in the CD group (p<0.05). The mean levels of
      lactobacilli increased from 4.9 to 7.2 in the VD group vs from 4.9 to 6.9 in the
      CD group. There was no statistical difference between two groups during the first
      week (p>0.05). The development of bifidobacteria and lactobacilli showed
      significant interindividual differences in all infants studied. CONCLUSIONS:
      Primary intestinal bifidobacteria in neonates by caesarean may be disturbed more
      significantly than lactobacilli.

PMID- 17507118
TI  - Adipose tissue arachidonic acid and the metabolic syndrome in Costa Rican adults.
AB  - BACKGROUND & AIMS: Arachidonic acid, a precursor to a series of inflammatory
      mediators, may contribute to the development of insulin resistance. We examined
      the association between adipose tissue arachidonic acid and the metabolic
      syndrome in Costa Rica, a country in which the metabolic syndrome is highly
      prevalent. METHODS: The 484 study participants each provided a fasting blood
      sample and an adipose tissue biopsy that was analyzed for fatty acid composition.
      Criteria for the metabolic syndrome were those established in the Third Report of
      the National Cholesterol Education Program Expert Panel. The data were analyzed
      by multivariate logistic regression. RESULTS: Subjects with greater adipose
      tissue arachidonic acid content had an increasing risk of the metabolic syndrome
      across quintiles: odds ratio (95% confidence interval), 1.00; 1.51 (0.78-2.91);
      2.40 (1.26-4.55); 3.50 (1.84-6.66); and 6.01 (3.11-11.61); test for trend,
      P<0.0001, after adjustment for age, gender and area of residence. Further
      adjustment for metabolic risk factors, including adipose fatty acids and body
      mass index, did not significantly modify the result. Adipose tissue arachidonic
      acid was also independently associated with abdominal obesity,
      hypertriglyceridemia, elevated fasting glucose, and high blood pressure.
      CONCLUSIONS: This study identifies arachidonic acid as an important independent
      marker of metabolic dysregulation. A better understanding of the role of this
      fatty acid in the pathogenesis of the metabolic syndrome is warranted.

PMID- 17507119
TI  - Physico-chemical characterisation and immunogenicity of a multi-valent candidate
      vaccine against non-typeable Haemophilus influenzae and Moraxella catarrhalis.
AB  - The physico-chemical characteristics and immunogenicity of a candidate vaccine
      against otitis media, prepared from recombinant lipidated outer membrane proteins
      (rLP4 and rLP6) from non-typeable Haemophilus influenzae (NTHi) and of the
      ubiquitous cell surface protein UspA2 from Moraxella catarrhalis, were evaluated.
      Optical spectroscopy, size exclusion chromatography and gel electrophoresis were
      used to characterise the purified protein components and assess their purity and
      molecular sizes. The results showed that the three proteins were highly purified.
      Possible dimers in rLP4, dimers and multimers in rLP6 and UspA2 were detected.
      Small amounts of rLP4 and rLP6 dimers and most of UspA2 complexes remained
      tightly bound even after SDS treatment under reducing conditions. Immunogenicity
      studies showed that all proteins induced substantial antibody responses in mice
      immunised with AlPO4-adsorbed rLP4, rLP6 or UspA2 or a combination of these
      proteins. However, combination of these proteins resulted in a reduced response
      to rLP4 and rLP6, but not to UspA2, suggesting interference between these
      proteins which should be taken into consideration during the development and
      evaluation of this vaccine.

PMID- 17507120
TI  - Immunogenicity and protective efficacy offered by a ribosomal-based vaccine from
      Shigella flexneri 2a.
AB  - Shigellosis is a major form of bacillary dysentery caused by Shigella infection.
      Shigella ribosome-based vaccines (SRV), considered among the potent vaccine
      candidates, are composed of O-antigen and ribosome isolated from S. flexneri 2a.
      To investigate the immunogenicity and protective efficacy of SRV, mice were
      vaccinated with SRV via the intranasal (i.n.) route. Interestingly, robust levels
      of Shigella-derived LPS-specific IgG and IgA Abs and antibody-forming cells were
      elicited in systemic and mucosal compartments following two i.n. administrations
      of SRV. Groups of mice receiving i.n. SRV developed milder pulmonary pneumonia
      upon challenge with virulent S. flexneri 2a than did those receiving parenteral
      SRV. We further found that the MyD88-dependent TLR2 signal partially mediates SRV
      induced mucosal immunity, with the exception of TLR4- and TLR5-governed innate
      immunity. Most importantly, polymeric immunoglobulin receptor knockout (pIgR-/-)
      mice, which lack secretory IgA Ab, were afforded less protective efficacy than
      were wild-type mice. It can be concluded then that SRV is immunogenic and
      provides protective efficacy in mice. It can also be surmised that a mucosal SRV
      vaccine would be particularly relevant in targeting shigellosis, which provokes
      inflammation in the human colon.

PMID- 17507121
TI  - NARAC: an emergency response resource for predicting the atmospheric dispersion
      and assessing the consequences of airborne radionuclides.
AB  - The National Atmospheric Release Advisory Center (NARAC) serves as a national
      resource for the United States, providing tools and services to quickly predict
      the environmental contamination and health effects caused by airborne
      radionuclides, and to provide scientifically based guidance to emergency managers
      for the protection of human life. NARAC's scientists have developed a diverse
      tool kit of numerical modeling capabilities to respond to different types of
      release events, distance scales (local, regional, continental, and global), and
      response times.

PMID- 17507122
TI  - Unusual presentation of adenoid cystic carcinoma mimicking a dentoalveolar
      fistula.

PMID- 17507123
TI  - An orbital apex fracture resulting in multiple cranial neuropathies.
AB  - Fractures of the orbital apex are rare after trauma, but can be devastating if
      associated with indirect traumatic optic neuropathy and a permanent visual
      defect. Computed tomography plays an important role in the diagnosis and
      classification of these fractures, but optimal treatment is controversial. We
      describe an isolated fracture of the orbital apex in a 15-year-old boy resulting
      in indirect traumatic optic neuropathy and palsies of cranial nerves III, IV and
      VI after a blunt injury to the face.

PMID- 17507124
TI  - Application of manure and compost to contaminated soils and its effect on zinc
      accumulation by Solanum nigrum inoculated with arbuscular mycorrhizal fungi.
AB  - Zn accumulation in Solanum nigrum grown in naturally contaminated soil in the
      presence of different types of organic amendments was assessed. Under the same
      conditions, the response of the plant to inoculation with two different isolates
      of arbuscular mycorrhizal fungi (AMF) (Glomus claroideum and Glomus intraradices)
      was also evaluated. S. nigrum grown in the non-amended soil always presented
      higher Zn accumulation in the tissues, with the addition of amendments inducing
      reductions of up to 80 and 40%, for manure and compost, respectively, and
      enhancing plant biomass yields. The establishment of S. nigrum in the Zn
      contaminated soil combined with the application of amendments led to a 70-80%
      reduction in the amount of Zn leached through the soil. The use of S. nigrum in
      combination with manure appeared as an effective method for reducing the effects
      of soil contamination, diminishing Zn transfer to other environmental
      compartments via percolation.

PMID- 17507125
TI  - Effects of housing condition on experimental outcome in a reproduction toxicity
      study.
AB  - In most toxicity studies single housing is still preferred, as social stress is
      believed to have an effect on experimental outcome through interaction with the
      toxic compound or by increasing variation. There are also arguments that single
      housing will have a similar effect. In this study the qualitative and
      quantitative effects of single- and social housing of rats has been investigated
      on immune- and endocrine responses, histopathology and body- and organ weights in
      a one-generation endocrine disrupter study (OECD 415) in rats exposed to
      tetrabromobisphenol A (TBBPA). The results of this study show that differences in
      parameters between the housing conditions were rarely noted. Striking results of
      the study are that in several parameters significant differences were noted in
      the un-dosed control group in single versus group housed animals, meaning that
      TBBPA can mask or enhance housing effects, or vice versa. In one case single
      housing altered the effect of the toxic compound. Depending on the endpoints of
      the study, the type of housing condition must be taken into consideration as
      findings like these could have great implications for the interpretation and
      validity of results from toxicological assays and the number of animals needed to
      detect significant effects of toxic compounds.

PMID- 17507127
TI  - Fetal gender and postpartum depression in a cohort of Chinese women.
AB  - To examine the relationship between fetal gender and postpartum depression, we
      conducted a cohort study in Changsha, Hunan, China between September 2004 and
      January 2005. Women aged 18-40 years with their first live birth of a singleton
      infant who came to hospital for postpartum examination at 6 weeks after
      childbirth were invited to participate. Women with known psychiatric disorders or
      a history of psychiatric disorders were excluded. Data on demographic and
      clinical information were collected. Postpartum depression was assessed by the
      Chinese version of the Edinburgh Postnatal Depression Scale. Fifty-two women
      (17.3%) were found to have postpartum depression. The rate of postpartum
      depression in women who gave birth to a female infant was 24.6% while the rate in
      those women who gave birth to a male infant was 12.2%. The relative risk for
      postpartum depression of women who gave birth to a female infant as compared with
      those who gave birth to a male was 2.89, after adjusting for potential
      confounding by maternal age, education level, family income, living condition,
      gravidity, number of prenatal care visits, and mode of delivery. We conclude that
      the risk of postpartum depression is increased in Chinese women who give birth to
      a female infant as compared to those who gave birth to a male infant. We
      speculate that this is associated with the negative reactions of family members
      towards the birth of a female baby.

PMID- 17507128
TI  - Family communication regarding inherited high cholesterol: why and how do
      patients disclose genetic risk?
AB  - Inadequate family communication concerning hereditary lipid disorders by index
      patients (IPs) may prevent their biological relatives from seeking testing and
      treatment. This lack of disclosure places the relatives at increased risk for
      cardiovascular disease. The present study, undertaken in the Netherlands,
      explored the reasons for family disclosure, and how disclosure was approached.
      Semi-structured interviews with 20 purposely sampled IPs revealed that they
      generally alerted their first-degree relatives of the genetic risk because they
      felt morally obliged to do so or because they were advised to do so by a health
      professional. However, IPs rarely alerted their more distant relatives due to
      insufficient risk knowledge or fear of being perceived as interfering in their
      relative's affairs. Furthermore, many IPs stated that they would not seek to
      persuade a relative to undergo testing out of respect for their autonomy.
      However, the findings did suggest that less direct methods were used for
      persuasion. An example would be stressing the severity of the condition.
      Consequently, the self-reported disclosures were incomplete and unbalanced.
      Typically, IPs provided information regarding the threat of inherited high
      cholesterol without furnishing information on means of coping with the risk. As
      IPs want and need professional support to help them disclose this information to
      their relatives, we suggest additional research about the ethical, practical and
      economic possibilities for this support.

PMID- 17507129
TI  - Antipsychotic medication, sedation and mental clouding: an observational study of
      psychiatric consultations.
AB  - Sedation and mental clouding are of concern to people on antipsychotic medication
      and are implicated in social withdrawal but their severity may be underestimated
      by psychiatrists. Existing studies of communication about adverse effects of
      medication are based on reports made by doctors or patients. This study is based
      on audiotapes of 92 outpatient consultations in two UK mental health trusts
      involving nine consultant psychiatrists where antipsychotic medication was
      discussed. When interviewed, these doctors and their colleagues had expressed a
      commitment to 'patient-centred' practice as well as recording concerns about the
      difficulties involved in the discussion of medication side effects. The study
      focuses on the ways in which sedation and mental clouding are presented and
      engaged with. Analysis of audiotape transcripts showed that patients raise these
      issues more often than doctors, contrasting with other adverse effects (such as
      blood changes) where doctors are more frequently the initiators of discussion.
      Sleepiness is sometimes presented by both patients and doctors as a part of
      normal experience and therefore to be welcomed. When presented as troublesome,
      patients' reports were sometimes met by doctors offering no response, changing
      the subject, or disagreeing with the patient's interpretation of the experience.
      Equally, there were some attempts by doctors to engage with patients' troubles
      and seek solutions. These could be unsuccessful where they involved challenges to
      the patients' medication-taking rationale, or more successful where they involved
      sympathetic and supportive listening. We speculate that the capacity to avoid
      addressing these problems is linked to the informal conversational style of these
      consultations, which means that concerns raised by one party can remain
      unaddressed without offending conversational norms. Doctors in these
      consultations are able to exercise considerable discretion over whether to define
      reports of sedation and mental clouding as medication-related problems.

PMID- 17507130
TI  - Anticipating ethical aspects of the use of biomarkers in the workplace: a tool
      for stakeholders.
AB  - This research aimed to understand how occupational health stakeholders
      represented the various ethical concerns raised by the use of biomarkers of
      exposure, effects and susceptibility to harmful agents. These representations
      were investigated by seven homogeneous focus group interviews and an Internet
      discussion forum. The following stakeholders took part in this research: workers,
      physicians, nurses, researchers, employers, industrial hygienists, trade-union
      representatives and employees of the Quebec Board of Health and Safety in the
      Workplace. The data were analyzed qualitatively using a constant comparison
      technique. The main ethical problems raised by the stakeholders were organized
      around three emergent themes: a narrative of science, the validation of
      biomarkers and the protection of workers. From these themes emanate the principal
      ethical problems raised by the stakeholders: confidentiality, the interpretation
      of data, consent and information, as well as an advantages/disadvantages ratio.
      These problems are described as ethical tension zones. The analysis also takes
      into account the impact of the representations that each group of stakeholders
      has of each other and the ethical problems that can arise. Because it is drawn
      from a study of stakeholders' representations, the resulting analytical model
      might also be used to anticipate the root of ethical problems generated by the
      use of the biomarkers in an occupational health context.

PMID- 17507131
TI  - Patient perspectives on information and choice in cancer screening: a qualitative
      study in the UK.
AB  - The principle of informed choice has been recently incorporated into cancer
      screening policy. However, there is limited empirical or theoretical work on
      informed choice in this particular context. The main aim of the study reported
      here was to explore the information needs of people invited for screening, and to
      gain insights into the relationship between the information they wanted and the
      choices they made. A qualitative study (nine focus groups and 15 individual
      interviews) was undertaken with people who had contrasting experiences (and
      outcomes) of either breast, cervical, or colorectal cancer screening at two
      locations in Scotland, UK. Findings suggest that lay people define and
      conceptualise informed choice differently from policy makers. The study also
      found that information about the disease was as important to people as
      information on the risks and limitations of screening. However, information may
      have little part to play in the choices people make. Rather, it may have more
      impact on outcomes such as satisfaction and anxiety. An explicit policy aim in
      promoting informed choice is to enhance patient autonomy and to prevent people
      from being deceived or coerced. However, this research shows that the provision
      of evidence-based information alone does not necessarily mean that an informed
      choice is made. People may not read, want, or understand the information, and,
      additionally, they may not be able to carry out their intended choice. There may
      be personal barriers, such as physical or mental health problems and language, or
      organisational barriers, such as the availability of the service/intervention and
      access. Therefore, the term 'informed choice' might not be useful in this
      context.

PMID- 17507132
TI  - Fears and beliefs of patients regarding cardiac catheterization.
AB  - The fears and beliefs patients hold about invasive medical interventions may
      affect their perceptions about risk and subsequent decisions to undergo those
      procedures. Little is known about fears and beliefs in patients undergoing
      invasive cardiac procedures and their relationship to perceptions of risks. Using
      a grounded theory approach, 10 men and 10 women referred for their first cardiac
      catheterization (CATH) from referral centers in Ontario, Canada were interviewed
      to identify fears and beliefs related to the procedure. Overall, women expressed
      more fears than men. Fears for both groups arose from: (1) lack of control about
      (i) physical aspects and (ii) psychosocial aspects of the CATH; (2) an unknown
      future; and (3) possible medical complications. Beliefs related to health
      personnel involved in the CATH, the technology used during the CATH and personal
      coping mechanisms. Men were more inclined to believe in technology, which
      overrode concerns about the procedure. Participants viewed CATH as a routine and
      necessary step in determining their future. Patients imputed previously held
      fears and beliefs and formulated new ones regarding the CATH during the process
      of anticipating the procedure. They viewed themselves as passive participants and
      not as actively consenting to the CATH. This paper offers previously undocumented
      insights from patients regarding CATH and provides the basis for developing
      future investigations.

PMID- 17507133
TI  - Shift of manual preference in right-handers following unimanual practice.
AB  - The effect of unimanual practice of the non-preferred hand on manual asymmetry
      and manual preference for sequential finger movements was evaluated in right
      handers before, immediately after, and 30 days following practice. The results
      demonstrate that unimanual practice induced a persistent shift of manual
      preference for the experimental task in most participants, but no significant
      correlation between manual asymmetry and manual preference was detected. These
      findings are explained by proposing that manual preference is influenced by a
      task-specific confidence developed from the recent history of differential use of
      the limbs, in interaction with a generalized confidence on a single hand for
      performance of motor skills.

PMID- 17507134
TI  - Repeated dose toxicity and developmental toxicity of diisopropanolamine to rats.
AB  - The repeated dose oral and dermal toxicity of diisopropanolamine (DIPA) was
      evaluated in rats and compared to the reported toxicity of the related secondary
      alcohol amine, diethanolamine (DEA). Fischer 344/DuCrl rats were given up to 750
      mg/kg/day by dermal application, 5 days/week, for 4 weeks; or up to 1,000 mg
      DIPA/kg/day by drinking water for 13 weeks to evaluate potential toxic effects.
      Time-mated female CRL:CD(SD) rats were given up to 1,000 mg/kg/day by gavage on
      gestation days (GD) 6-20 for evaluation of maternal and fetal effects. In the
      dermal toxicity study, no adverse treatment-related in-life effects other than
      mild irritation at the site of dermal application at >or= 500 mg/kg/day were
      observed. There were no systemic effects in rats given up to 750 mg/kg/day. In
      the subchronic oral toxicity study, the most significant effects were an increase
      in absolute and relative kidney weights, unaccompanied by histopathologic
      changes, at >or= 500 mg/kg/day DIPA. The latter effect was ameliorated following
      a 4-week recovery period. In the developmental toxicity study, there were no
      maternal or developmental effects at any dose level evaluated. The toxicity of
      DIPA contrasts with that of DEA which has been shown to affect a number of organ
      systems when repeatedly administered orally or dermally at similar or lower
      dosages.

PMID- 17507135
TI  - Synthesis and characterization of deoxynivalenol glucuronide: its comparative
      immunotoxicity with deoxynivalenol.
AB  - Deoxynivalenol (DON) is a mycotoxin commonly contaminating wheat, barley and
      corn. DON glucuronide (DONGLU) is a major DON metabolite. We synthesized and
      purified DONGLU and tested its immunotoxicity, hypothesizing that DONGLU would be
      much less toxic to K562 cells compared with DON. DONGLU was synthesized using rat
      liver microsomes, uridine-5'-diphosphoglucuronic acid and DON, and purified with
      a Sephadex LH-20 column and reverse phase HPLC. beta-Glucuronidase hydrolysis
      formed a product with retention time and UV spectrum identical with DON. Using
      atmospheric pressure chemical ionization in negative mode, the molecular mass (M
      1) of purified DONGLU was 471 g/mol; in agreement with an expected molecular
      weight of 472 g/mol. MS and NMR indicated that the glucuronide moiety was
      conjugated with the carbon-3-hydroxyl group of DON. The cytotoxicity of DON and
      DONGLU were compared in cell culture using human erythroleukemia cell line K562.
      Fifty percent inhibition of cell number was observed with a DON concentration of
      1.31 microM using a methylthaizol tetrazolium (MTS) cell viability assay whereas
      no significant cytotoxicity was observed for DONGLU at up to 270 microM. DONGLU
      did not influence DON toxicity at 0.5 microM, 1.3 microM and 8.4 microM
      concentration combinations of each compound. These data verified that DONGLU is a
      detoxification product of DON.

PMID- 17507137
TI  - Regulatory perspectives of Type II prodrug development and time-dependent
      toxicity management: nonclinical Pharm/Tox analysis and the role of comparative
      toxicology.
AB  - Many therapeutic agents are prepared in prodrug forms, which are classified into
      Type I, II and subtypes A, B based on their sites of conversion. Recently, an
      increasing number of INDs have appeared as Type II prodrugs that often contain
      dual tracks of toxicity profile exploration, one on the prodrug and another on
      the active drug. A comparative toxicology analysis is introduced here to assist
      reviewers to evaluate the dual toxicity profiles effectively. The analysis helps
      determine which toxicity is contributed by the prodrug itself, its intermediates,
      or the active drug itself. As prodrug INDs, or any other new molecular entity
      (NME) INDs progress into advanced phases of toxicology development, analysis of
      time-dependent component of toxicity expression, regarding the emergence of new
      target organs over time, becomes more significant. A strategy is developed to
      address Pharm/Tox issues such as what duration is required for a toxicity to
      emerge at the exposure level achieved or dose studied, how many animals in the
      group are affected, whether the toxicity is a cross-species phenomenon, and
      whether it is reversible, etc. In conclusion, dual-track comparative toxicology
      can be useful in the understanding of Type II prodrug's mechanism of toxicity,
      and that time-dependent toxicology analysis offers means to detecting new
      toxicity emergence over time. Both approaches could significantly facilitate
      secondary and tertiary review processes during IND development of a prodrug or
      NME.

PMID- 17507138
TI  - Does compression-only cardiopulmonary resuscitation generate adequate passive
      ventilation during cardiac arrest?
AB  - INTRODUCTION: The need for rescue breaths in bystander CPR has been questioned
      after several studies have shown that omitting ventilation does not worsen
      outcome. Chest compression may produce passive tidal volumes large enough to
      provide adequate ventilation in animal studies, but no recent clinical studies
      have examined this phenomenon. We measured passive ventilation during optimal
      chest compression to determine whether compression-only CPR provides adequate gas
      exchange during cardiac arrest. METHODS: Adult cardiac arrest patients were
      treated according to European Resuscitation Council guidelines. Chest
      compressions were performed using a mechanical chest compression device (LUCAS)
      with active decompression disabled to mimic manual compression. Respiratory
      variables were measured during periods of compression-only CPR. RESULTS:
      Emergency Department data were collected during compression-only CPR from 17
      patients (11 male) aged 47-82 years who had suffered an out-of-hospital cardiac
      arrest. Median tidal volume per compression was 41.5 ml (range 33.0-62.1 ml),
      being considerably less than measured deadspace in all patients. Maximum end
      tidal CO2 was 0.93 kPa (range 0.0-4.6 kPa). Minute volume CO2 was 19.5 ml (range
      15.9-33.8; normal range 150-180 ml). CONCLUSIONS: At an advanced stage of cardiac
      arrest, passive ventilation during compression-only CPR is limited in its ability
      to maintain adequate gas exchange, with gas transport mechanisms associated with
      high frequency ventilation perhaps generating a very limited gas exchange. The
      effectiveness of passive ventilation during the early stages of CPR, when chest
      and lung compliance is greater, remains to be investigated.

PMID- 17507139
TI  - Chest radiograph during therapeutic hypothermia--ice packs mimicking subcutaneous
      emphysema.

PMID- 17507140
TI  - Successful extracorporeal life support after potentially fatal pulmonary oedema
      caused by inhalation of nitric and hydrofluoric acid fumes.
AB  - Two patients presented with potentially fatal pulmonary oedema after accidental
      exposure to nitric and hydrofluoric acid fumes during electroplating. Despite
      aggressive respiratory support, one succumbed to respiratory failure 3.5h after
      inhalation. The other patient also rapidly progressed to respiratory failure.
      Extracorporeal life support (ECLS) was started 5h after exposure at the ED.
      During ECLS, hypoxia improved, but pulmonary oedema shown by chest radiography
      became aggravated. N-Acetyl cysteine and calcium gluconate were given i.v. on the
      first day of admission and nebulised for 48 h after exposure. Pulmonary
      secretions were significantly reduced 24 h after the nebulising therapy began.
      Ultimately, the patient was discharged without serious pulmonary or neurological
      complications after 28 days of hospitalisation. In this case, early ECLS,
      nebulised antioxidant and antidote were available to treat potentially fatal
      pulmonary oedema after exposure to nitric and hydrofluoric acid fumes.

PMID- 17507141
TI  - Ambient oxygen concentrations resulting from use of the Lund University
      Cardiopulmonary Assist System (LUCAS) device during simulated cardiopulmonary
      resuscitation.
AB  - INTRODUCTION: Supplementary oxygen is used routinely during cardiopulmonary
      resuscitation (CPR). High ambient oxygen levels from ventilation circuits have
      caused fatal fires and explosions. The Lund University Cardiopulmonary Assist
      System (LUCAS) device is driven by > 70 l min(-1) oxygen which is also likely to
      increase ambient oxygen concentrations and cause similar risk of fire and
      explosion. This study used simulated CPR with a LUCAS device to measure resulting
      ambient oxygen concentrations and assess safety of the device. MATERIAL AND
      METHODS: Simulated manikin CPR using a LUCAS device was performed outdoors,
      inside an ambulance (ventilation off and ventilation on full power), and in a
      resuscitation bay. Ambient oxygen concentrations were measured over the apical
      and sternal defibrillation sites and midway between the two, at the head and 1m
      horizontally above the head. Recordings were made for 5 min when the LUCAS device
      was turned on and for a further 5 min when turned off. RESULTS: Ambient oxygen
      concentration increased quickly in all four scenarios. Peak oxygen levels over
      the chest were highest in the resuscitation bay (36.7%) and lowest in the
      ambulance with ventilation on full power (33.8%). Oxygen levels decreased to
      baseline within 5 min of turning off the LUCAS device. CONCLUSION: The use of
      oxygen to drive the LUCAS device results in a rapid increase in ambient oxygen
      concentration to levels likely to risk injury or death from fire. Ambulance
      services and hospitals using the device must be alerted to these dangers
      immediately.

PMID- 17507142
TI  - Cool waves: resolution of Osborn waves after prolonged hypothermia.

PMID- 17507143
TI  - The functional and anatomical organization of marsupial neocortex: evidence for
      parallel evolution across mammals.
AB  - Marsupials are a diverse group of mammals that occupy a large range of habitats
      and have evolved a wide array of unique adaptations. Although they are as diverse
      as placental mammals, our understanding of marsupial brain organization is more
      limited. Like placental mammals, marsupials have striking similarities in
      neocortical organization, such as a constellation of cortical fields including
      S1, S2, V1, V2, and A1, that are functionally, architectonically, and
      connectionally distinct. In this review, we describe the general lifestyle and
      morphological characteristics of all marsupials and the organization of
      somatosensory, motor, visual, and auditory cortex. For each sensory system, we
      compare the functional organization and the corticocortical and thalamocortical
      connections of the neocortex across species. Differences between placental and
      marsupial species are discussed and the theories on neocortical evolution that
      have been derived from studying marsupials, particularly the idea of a
      sensorimotor amalgam, are evaluated. Overall, marsupials inhabit a variety of
      niches and assume many different lifestyles. For example, marsupials occupy
      terrestrial, arboreal, burrowing, and aquatic environments; some animals are
      highly social while others are solitary; different species are carnivorous,
      herbivorous, or omnivorous. For each of these adaptations, marsupials have
      evolved an array of morphological, behavioral, and cortical specializations that
      are strikingly similar to those observed in placental mammals occupying similar
      habitats, which indicate that there are constraints imposed on evolving nervous
      systems that result in recurrent solutions to similar environmental challenges.

PMID- 17507144
TI  - Nephron injury induced by diagnostic ultrasound imaging at high mechanical index
      with gas body contrast agent.
AB  - The right kidney of anesthetized rats was imaged with intermittent diagnostic
      ultrasound (1.5 MHz; 1-s trigger interval) under exposure conditions simulating
      those encountered in human perfusion imaging. The rats were infused intravenously
      with 10 microL/kg/min Definity (Bristol-Myers Squibb Medical Imaging, Inc., N.
      Billerica, MA, USA) while being exposed to mechanical index (MI) values of up to
      1.5 for 1 min. Suprathreshold MI values ruptured glomerular capillaries,
      resulting in blood filling Bowman's space and proximal convoluted tubules of many
      nephrons. The re-establishment of a pressure gradient after hemostasis caused the
      uninjured portions of the glomerular capillaries to resume the production of
      urinary filtrate, which washed some or all of the erythrocytes out of Bowman's
      space and cleared blood cells from some nephrons into urine within six hours.
      However, many of the injured nephrons remained plugged with tightly packed red
      cell casts 24 h after imaging and also showed degeneration of tubular epithelium,
      indicative of acute tubular necrosis. The additional damage caused by the
      extravasated blood amplified that caused by the original cavitating gas body.
      Human nephrons are virtually identical to those of the rat and so it is probable
      that similar glomerular capillary rupture followed by transient blockage and/or
      epithelial degeneration will occur after clinical exposures using similar high MI
      intermittent imaging with gas body contrast agents. The detection of blood in
      postimaging urine samples using standard hematuria tests would confirm whether or
      not clinical protocols need to be developed to avoid this potential for
      iatrogenic injury.

PMID- 17507145
TI  - Ultrasound at 27 kHz increases tissue expression and activity of nitric oxide
      synthases in acute limb ischemia in rabbits.
AB  - Transcutaneous low-frequency ultrasound (US) preserves myocardial and skeletal
      muscle viability by increasing tissue perfusion through an undefined nitric oxide
      (NO)-dependent mechanism. We have examined whether US increases tissue expression
      and activity of the three nitric oxide synthase (NOS) isoforms: endothelial
      (eNOS), neuronal (nNOS) and inducible (iNOS). The two femoral arteries of four
      New Zealand rabbits were ligated for a total of 120 min. After 60 min of
      ligation, transcutaneous low-frequency US (27 kHz, 0.13 W/cm2) was applied for 60
      min to one thigh, while the contra-lateral artery served as a control (total
      ischemia time=120 min). Calcium-dependent (cNOS) and -independent (ciNOS) NOS
      activity, and concentration of total eNOS, ser-1177 phosphorylated eNOS (P-eNOS),
      nNOS and iNOS were then determined in the gracilis muscle. Compared with the
      control, US application significantly increased cNOS activity [3.34+/-0.28 versus
      3.87+/-0.10x1000 counts per minute (cpm), respectively, p=0.031] and ciNOS
      activity (1.99+/-0.09 versus 3.26+/-0.68 cpm, respectively, p<0.001). Western
      immunoblotting revealed a significant increase in protein content of both iNOS
      (184.5+/-1.08%; p<0.0001) and P-eNOS (381.5+/-2.47%; p<0.001), with only a small
      increase in total eNOS and nNOS expression. In conclusion, application of
      transcutaneous low-frequency US to ischemic muscular tissue significantly
      increases both cNOS and ciNOS activity by increasing eNOS phosphorylation and
      iNOS expression, respectively.

PMID- 17507146
TI  - ECG-gated, mechanical and electromechanical wave imaging of cardiovascular
      tissues in vivo.
AB  - In simplistic terms, the motion of the heart can be summarized as an active
      contraction and passive relaxation of the myocardium. However, the local motion
      of cardiovascular tissues over the course of an entire cardiac cycle results from
      various transient events such as the valves closing/opening, sudden changes in
      blood pressure and electrical conduction of the myocardium. The transient motion
      generated by most of these events occurs within a very short time (on the order
      of 1 ms) and cannot be imaged correctly with conventional imaging systems, due to
      their limited temporal resolution. In this paper, we propose a method for imaging
      this rapid transient motion of tissues in cardiovascular applications. Our method
      is based on imaging tissues with ultrasound at high frame rates (up to 8000 fps)
      by synchronizing the two-dimensional (2D) image acquisition on the
      electrocardiogram (ECG) signals. In vivo feasibility is demonstrated in
      anesthetized mice. The propagation of several transient mechanical waves was
      imaged in different regions of the myocardium and the wave phase velocities were
      found to be between 0.44 m/s and 5 m/s. These waves may be generated by either a
      purely mechanical effects or through electromechanical coupling in the myocardium
      depending on the phase of the cardiac cycle, in which they occur. The abdominal
      aorta was also imaged using the same technique and the propagation of a
      mechanical pulse wave was imaged. The pulse wave velocity was measured and the
      Young's modulus of the vessel wall was derived based on the Moens-Korteweg
      equation. This method could potentially be used for mapping the stiffness of the
      myocardium and the artery walls and may lead to the early diagnosis of
      cardiovascular diseases.

PMID- 17507147
TI  - A cumulative shear mechanism for tissue damage initiation in shock-wave
      lithotripsy.
AB  - Evidence suggests that inertial cavitation plays an important role in the renal
      injury incurred during shock-wave lithotripsy. However, it is unclear how tissue
      damage is initiated, and significant injury typically occurs only after a
      sufficient dose of shock waves. Although it has been suggested that shock-induced
      shearing might initiate injury, estimates indicate that individual shocks do not
      produce sufficient shear to do so. In this paper, we hypothesize that the
      cumulative shear of the many shocks is damaging. This mechanism depends on
      whether there is sufficient time between shocks for tissue to relax to its
      unstrained state. We investigate the mechanism with a physics-based simulation
      model, wherein the basement membranes that define the tubules and vessels in the
      inner medulla are represented as elastic shells surrounded by viscous fluid.
      Material properties are estimated from in-vitro tests of renal basement membranes
      and documented mechanical properties of cells and extracellular gels. Estimates
      for the net shear deformation from a typical lithotripter shock (approximately
      0.1%) are found from a separate dynamic shock simulation. The results suggest
      that the larger interstitial volume (approximately 40%) near the papilla tip
      gives the tissue there a relaxation time comparable to clinical shock delivery
      rates (approximately 1 Hz), thus allowing shear to accumulate. Away from the
      papilla tip, where the interstitial volume is smaller (approximately 20%), the
      model tissue relaxes completely before the next shock would be delivered.
      Implications of the model are that slower delivery rates and broader focal zones
      should both decrease injury, consistent with some recent observations.

PMID- 17507149
TI  - Editorial comment on: Retroperitoneal lymph node dissection (RPLD) in conjunction
      with nephroureterectomy in the treatment of infiltrative transitional cell
      carcinoma (TCC) of the upper urinary tract: impact on survival.

PMID- 17507148
TI  - Retroperitoneal lymph node dissection (RPLD) in conjunction with
      nephroureterectomy in the treatment of infiltrative transitional cell carcinoma
      (TCC) of the upper urinary tract: impact on survival.
AB  - OBJECTIVES: To evaluate the prognostic impact of retroperitoneal lymph node
      dissection (RPLD) performed during nephroureterectomy on time to recurrence and
      survival in patients with infiltrative transitional cell carcinoma (TCC) of the
      upper urinary tract. METHODS: The charts of 82 patients with T2-T4 TCC of the
      upper tract were retrospectively reviewed. The median patient age was 67.7 yr.
      Seventy-nine patients underwent nephroureterectomy and three had partial
      nephrectomy. Forty patients (48.8%) had RPLD with removal of more than five nodes
      after nephroureterectomy (group 1), whereas 42 (51.2%) had nephroureterectomy
      only (group 2). Median follow-up was 64.7 mo. The prognostic role of RPLD, T (2
      vs. 3-4), G (2 vs. 3), N (0 vs. 1-2 vs. x), age (<65 vs. >65 yr) and sex on time
      to recurrence and survival were evaluated. RESULTS: Median time to recurrence and
      overall survival were 51.2 and 52.5 mo, respectively, in group 1 and 18.5 and
      21.2 mo in group 2. Univariate analysis demonstrated that RPLD and T and N status
      were significantly related both to time to recurrence (p=0.009, 0.008, and 0.009,
      respectively) and survival (p=0.000006, 0.003, and 0.003). When analyzed using
      the Cox proportional hazard model, RPLD and T category were the only two factors
      demonstrating independent significance on overall survival (p=0.004 and 0.008).
      CONCLUSIONS: The results indicate a possible curative role of RPLD in the
      treatment of patients with infiltrative TCC of the upper urinary tract. Further
      randomized trials are needed to confirm these results.

PMID- 17507150
TI  - Laparoscopic extended pelvic lymph node dissection for prostate cancer:
      description of the surgical technique and initial results.
AB  - OBJECTIVE: In patients with prostate cancer, extended pelvic lymph node
      dissection (ePLND) yields a higher number of lymph node metastases (LNM) than
      standard pelvic lymph node dissection (PLND) of the obturator fossa only. We
      describe our laparoscopic technique of extended lymph node dissection and provide
      the number and locations of positive lymph nodes from our experience. METHODS: In
      a total of 35 selected patients with clinically localized prostate cancer,
      laparoscopic ePLND was performed prior to laparoscopic radical prostatectomy. The
      template included the genitofemoral nerve up to the bifurcation of the common
      iliac artery and down to the epigastric artery. In the "split and roll" technique
      the internal and external iliac arteries including the bifurcation and the
      external iliac vein were completely mobilized. After freeing the obturator nerve,
      the entire lymph node package was released from the pelvic side wall. RESULTS:
      Mean operative time was 90min/patient. The complications were two temporary and
      reversible neurapraxias (ischiatic nerve and obturator nerve), one deep vein
      thrombosis, and two lymphoceles. One lymphocele healed conservatively; the second
      was marsupialized laparoscopically. Eleven (31.4%) patients had lymph node
      metastases; their mean prostate-specific antigen (PSA) level was 20.3+/-7.0 ng/ml
      (range: 5.2-39.7 ng/ml) and their median Gleason sum in biopsy was 7 (range: 6
      8). Mean size of the LNM was 3.1+/-1.0 mm (range: 0.2-8). In 5 of the 11 patients
      with LNM these were detected exclusively outside the obturator fossa. LNM were in
      the obturator fossa only in two (one bilateral), around the external iliac artery
      only in two, around the internal iliac artery only in two, and around the
      external iliac artery and internal iliac only in one patient. CONCLUSIONS:
      Laparoscopic ePLND can be combined with laparoscopic radical prostatectomy.
      Standardization of the technique facilitates surgery to a great extent. e-PLND
      detects LNM in a significant number of patients. The majority of LNM are outside
      the obturator fossa. The transperitoneal approach allows a wide exposure and is
      the most important factor to enable successful ePLND.

PMID- 17507151
TI  - Obesity and prostate cancer: epidemiology and clinical implications.
AB  - OBJECTIVES: Both obesity and prostate cancer (PCa) are epidemic in Western
      society. Although initial epidemiological data appeared conflicting, recent
      studies have clarified the association between obesity and PCa. Therefore, we
      sought to review the epidemiological data linking obesity and PCa with an
      emphasis on the clinical implications and how to improve outcomes among obese
      men. METHODS: A PubMed search using the keywords "prostate cancer" and "obesity"
      was performed. Relevant articles and references were reviewed for data on the
      association between obesity and PCa. RESULTS: Recent data suggest obesity is
      associated with reduced risk of nonaggressive disease but increased risk of
      aggressive disease. This observation may be explained in part by an inherent bias
      in our ability to detect PCa in obese men (lower PSA values and larger sized
      prostates, making biopsy less accurate for finding an existent cancer), which
      ultimately leads to increased risk of cancer recurrence after primary therapy and
      increased PCa mortality. Despite this detection bias potentially contributing to
      more aggressive cancers, multiple biological links also exist between obesity and
      PCa including higher estradiol, insulin, free IGF-1, and leptin levels, and lower
      free testosterone and adiponectin levels, all of which may promote more
      aggressive cancers. CONCLUSIONS: The association between obesity and PCa is
      complex. Emerging data suggest obesity increases the risk of aggressive cancer,
      while simultaneously decreasing the risk of more indolent disease. This is likely
      driven by both "biological" and "nonbiological" causes. Simple changes in
      clinical practice patterns can reduce the impact of nonbiological causes and may
      help improve PCa outcomes among obese men.

PMID- 17507152
TI  - The use of local anesthesia with N-DO injector (Physion) for transurethral
      resection (TUR) of bladder tumors and bladder mapping: preliminary results and
      cost-effectiveness analysis.
AB  - OBJECTIVE: We evaluated feasibility of TUR of Ta-T1 TCC of the bladder or bladder
      mapping under local anesthesia using a Physion endoinjector to see if correct
      tumor staging was possible, to check patient tolerability, and to analyze cost
      effectiveness. METHODS: Thirty patients with bladder tumors and 10 patients with
      hematuria and/or doubtful cytologies were treated in a day hospital setting. TUR
      or biopsies were performed after injecting lidocaine into the outer area of the
      lesion in the bladder at 2-3 sites under the mucosa. A single injection per
      biopsy site was necessary for bladder mapping. We evaluated tolerability using
      the VAS questionnaire. Cost analysis considered length of hospital stay, number
      of anesthesiological procedures, and complications. RESULTS: The stage and grade
      after TUR were 19 TaG1-2, 10 T1G2, and 1 papillary hyperplasia. After bladder
      mapping, 5 patients had CIS and 5 had inflammation. Sixty percent of patients had
      no or mild pain, 30% moderate pain requiring light sedation or analgesia, and 10%
      severe pain requiring spinal or general anesthesia. The mean hospital stay was
      9h. Four of 40 patients complained of macroscopic hematuria; one was readmitted
      to the ward. This procedure saved 1097.07 euros per case and 36 anesthesiological
      procedures were avoided. CONCLUSIONS: This is a simple, safe, cost-effective
      technique, allowing TUR of bladder tumors and bladder mapping in 60% of patients
      and, with light sedation or analgesia, in 90% of patients, with a low
      complication rate. Tumor staging was correct in 90% of cases. The mean hospital
      stay was 9h.

PMID- 17507153
TI  - Editorial comment on: The use of local anesthesia with N-DO Injector (Physion)
      for transurethral resection (TUR) of bladder tumors and bladder mapping:
      preliminary results and cost-effectiveness analysis.

PMID- 17507154
TI  - Editorial comment on: The use of local anesthesia with N-DO injector (physion)
      for transurethral resection (TUR) of bladder tumors and bladder mapping:
      preliminary results and cost-effectiveness analysis.

PMID- 17507155
TI  - Involvement of Ca2+-mediated apoptotic signals in palmitate-induced MIN6N8a beta
      cell death.
AB  - The extracellular Ca(2+) chelator EGTA and L-type Ca(2+) channel blockers, such
      as, nifedipine and nimodipine were found to have a protective effect on palmitate
      induced MIN6N8a beta cell apoptosis, whereas the Ca(2+) channel opener, Bay
      K8644, enhanced the apoptotic process. Moreover, the phospho-form of Bad, in
      conjunction with phospho-Akt, was reduced in response to palmitate and the
      palmitate-induced dephosphorylations of Akt and Bad were dependent on Ca(2+)
      influx. The transient expression of catalytically active Akt prevented MIN6N8a
      cells from palmitate-induced apoptosis. Deltamethrin, an inhibitor of Ca(2+)
      activated phosphatase, delayed Akt and Bad dephosphorylations, and then protected
      MIN6N8a cells from palmitate-induced apoptosis. On the other hand, palmitate was
      found to induce CHOP, an apoptotic transcription factor in response to ER stress,
      and this induction was enhanced by Ca(2+) influx. Our studies suggested that
      Ca(2+) influx and subsequent Ca(2+)-mediated apoptotic signals are involved in
      palmitate-induced beta cell death.

PMID- 17507156
TI  - SPECT revealed cortical dysfunction in a patient who had genetically definite
      megalencephalic leukoencephalopathy with subcortical cysts.
AB  - We describe the findings on single photon emission computed tomography (SPECT) in
      a patient who had genetically definite megalencephalic leukoencephalopathy with
      subcortical cysts. Technetium-99m-ethyl cysteinate dimer SPECT revealed
      hypoperfusion in the cerebral white matter, which had shown high signal intensity
      on magnetic resonance imaging (MRI) T2 images. Hypoperfusion was also
      unexpectedly found in the frontal cortices, which showed no abnormalities on MRI.
      This frontal abnormality corresponded clinically to a low score on the frontal
      assessment battery. Decreased GABA receptor density as suggested by (123)I
      Iomazenil SPECT provided further evidence of cortical neuron dysfunction.
      Although confirmation must await future larger-scale SPECT and functional
      studies, our findings suggest that SPECT can be used to non-invasively monitor in
      vivo cortical function in this disease.

PMID- 17507157
TI  - Application of acidogenic fixed-bed reactor prior to anaerobic membrane
      bioreactor for sustainable slaughterhouse wastewater treatment.
AB  - High rate anaerobic treatment systems such as anaerobic membrane bioreactors
      (AMBR) are less popular for slaughterhouse wastewater due to the presence of high
      fat oil and suspended matters in the effluent. This affects the performance and
      efficiency of the treatment system. In this work, AMBR has been tried for
      slaughterhouse wastewater treatment. After the start up period, the reactor was
      operated with an average organic loading rate (OLR) of 4.37 kg TCODm(-3)d(-1)
      with gradual increase to an average of 13.27 kg TCODm(-3)d(-1). At stable
      conditions, the treatment efficiency was high with an average COD and BOD(5)
      reduction of 93.7 and 93.96%, respectively. However, a reduction in the AMBR
      performance was shown with the increase of the OLR to 16.32 kg TCODm(-3)d(-1).
      The removal efficiencies of SCOD and BOD(5) were drastically decreased to below
      53.6 and 73.3%, respectively. The decrease of the AMBR performance was due to the
      accumulation of VFAs. Thus, a new integrated system composed of a FBR for the
      acidogenesis step followed by the AMBR for methanogenesis step was developed. At
      high ORL, the integrated system improved the performance of the anaerobic
      digestion and it successfully overcame the VFA accumulation problem in the AMBR.
      The anaerobic treatment led to a total removal of all tested pathogens. Thus, the
      microbiological quality of treated wastewater fits largely with WHO guidelines.

PMID- 17507158
TI  - Chromium and zinc uptake by algae Gelidium and agar extraction algal waste:
      kinetics and equilibrium.
AB  - Biosorption of chromium and zinc ions by an industrial algal waste, from agar
      extraction industry has been studied in a batch system. This biosorbent was
      compared with the algae Gelidium itself, which is the raw material for agar
      extraction, and the industrial waste immobilized with polyacrylonitrile
      (composite material). Langmuir and Langmuir-Freundlich equilibrium models
      describe well the equilibrium data. The parameters of Langmuir equilibrium model
      at pH 5.3 and 20 degrees C were for the algae, q(L)=18 mg Cr(III)g(-1) and 13
      mgZn(II)g(-1), K(L) = 0.021l mg(-1)Cr(III) and 0.026l mg(-1) Zn(II); for the
      algal waste, q(L)=12 mgCr(III)g(-1) and 7mgZn(II)g(-1), K(L)=0.033lmg(-1) Cr(III)
      and 0.042l mg(-1) Zn(II); for the composite material, q(L) = 9 mgCr(III)g(-1) and
      6 mgZn(II)g(-1), K(L)=0.032l mg(-1)Cr(III) and 0.034l mg(-1)Zn(II). The
      biosorbents exhibited a higher preference for Cr(III) ions and algae Gelidium is
      the best one. The pseudo-first-order Lagergren and pseudo-second-order models
      fitted well the kinetic data for the two metal ions. Kinetic constants and
      equilibrium uptake concentrations given by the pseudo-second-order model for an
      initial Cr(III) and Zn(II) concentration of approximately 100 mgl(-1), at pH 5.3
      and 20 degrees C were k(2,ads)=0.04 g mg(-1)Cr(III)min(-1) and 0.07 g mg(
      1)Zn(II)min(-1), q(eq)=11.9 mgCr(III)g(-1) and 9.5 mgZn(II)g(-1) for algae;
      k(2,ads)=0.17 g mg(-1)Cr(III)min(-1) and 0.19 g mg(-1)Zn(II)min(-1), q(eq)=8.3
      mgCr(III)g(-1) and 5.6 mgZn(II)g(-1) for algal waste; k(2,ads)=0.01 g mg(
      1)Cr(III)min(-1) and 0.18 g mg(-1)Zn(II)min(-1), q(eq)=8.0 mgCr(III)g(-1) and 4.4
      mgZn(II)g(-1) for composite material. Biosorption was modelled using a batch
      adsorber mass transfer kinetic model, which successfully predicts Cr(III) and
      Zn(II) concentration profiles. The calculated average homogeneous diffusivities,
      D(h), were 4.2 x 10(-8), 8.3 x 10(-8) and 1.4 x 10(-8)cm(2)s(-1) for Cr(III) and
      4.8 x 10(-8), 9.7 x 10(-8) and 6.2 x 10(-8)cm(2)s(-1) for Zn(II), respectively,
      for Gelidium, algal waste and composite material. The algal waste has the lower
      intraparticle resistance.

PMID- 17507159
TI  - Infrared spectroscopy: a new diagnostic tool in Alzheimer disease.
AB  - Biological markers play an evolving role in the diagnosis of Alzheimer disease
      (AD). We compare conventional measurements of cerebrospinal fluid (CSF) tau and
      beta-amyloid(1-42) proteins to a novel approach - Fourier transformed infrared
      (FT-IR) spectroscopy - a simple technique derived from chemical and physical
      sciences that characterizes intramolecular bonds. For automatic diagnostic
      analysis, we developed an artificial neural network (ANN). We examined 71
      patients with a clinical diagnosis of AD and 66 controls. beta-Amyloid(1-42) was
      decreased (sensitivity 80% and specificity 78%); tau was elevated (sensitivity
      76% and specificity 88%) in CSF of AD patients. The combined tau/beta-amyloid(1
      42) quotient was able to distinguish healthy from diseased subjects with 99%
      sensitivity and 86% specificity. The ANN could separate FT-IR spectroscopy data
      with 88.5% sensitivity and 80% specificity. FT-IR spectroscopy proved to be cost
      effective and simple to perform. Diagnostic sensitivity and specificity is in the
      range of CSF tau and beta-amyloid(1-42) protein analysis. Larger sample numbers
      for ANN training and validation could increase diagnostic accuracy and thus prove
      to be a useful screening tool.

PMID- 17507160
TI  - ERP correlates of transposed-letter similarity effects: are consonants processed
      differently from vowels?
AB  - Recent research has shown that pseudowords created by transposing letters are
      very effective for activating the lexical representation of their base words
      (e.g., relovution activates REVOLUTION). Furthermore, pseudoword transpositions
      of consonants are more similar to their corresponding base words than the
      transposition of vowels. We report one experiment using pseudowords created by
      the transposition of two consonants, two vowels, and their corresponding control
      conditions (i.e., the replacement of two consonants or two vowels) in a lexical
      decision task while Event Related Potentials (ERPs) were recorded. The results
      showed a modulation of the amplitude of the N400 component as a function of the
      type of pseudoword (transposed-letter versus replacement letter pseudowords), and
      this modulation was different for transposed consonants and vowels. These results
      suggest that consonants and vowels play a different role during word processing.

PMID- 17507161
TI  - Appearance pattern of TDP-43 in Japanese frontotemporal lobar degeneration with
      ubiquitin-positive inclusions.
AB  - TAR-DNA-binding protein 43 (TDP-43) was identified as a major component of
      ubiquitin-positive intracellular inclusions from brains of patients with
      frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U).
      Here, we immunohistochemically investigated the appearance pattern of TDP-43 to
      compare the distribution of TDP-43-positive structures with that of ubiquitin
      positive structures in brains of seven patients with Japanese FTLD-U, five of
      atypical Pick's disease (aPiD) and two of dementia with motor neuron disease (D
      MND), as well as two patients with PiD as control. TDP-43-immunoreactivity
      generally colocalized to ubiquitin-immunoreactivity in both neuronal cytoplasmic
      inclusions and neurites in FTLD-U brains, but TDP-43-immunoreactivity alone or
      ubiquitin-immunoreactivity alone was also observed. In five aPiD cases, double
      immunostaining with TDP-43 and ubiquitin demonstrated that diffuse neuronal
      cytoplasmic immunostaining for ubiquitin did not always display TDP-43
      immunoreactivity. In contrast, ubiquitin-positive neuronal cytoplasmic inclusions
      usually displayed TDP-43-immunoreactivity in two D-MND cases, although most glial
      inclusions in one of two cases were immunostained only for TDP-43. TDP-43
      positive structures were not detected in two PiD cases. Thus, the ratio in the
      appearance pattern of TDP-43 and ubiquitin was different between aPiD and D-MND,
      leading to the hypothesis that this difference may be associated with the two
      pathogenic variants related to clinical and pathological heterogeneity in FTLD-U.

PMID- 17507162
TI  - Electrophysiological and immunofluorescence characterization of Ca(2+) channels
      of acutely isolated rat sphenopalatine ganglion neurons.
AB  - The sphenopalatine ganglion (SPG) is the main parasympathetic ganglion that is
      involved in regulating cerebral vascular tone and gland secretion. SPG neurons
      have been implicated in some types of migraine headaches but their precise role
      has yet to be determined. In addition, very little information is available
      regarding ion channel modulation by neurotransmitters that are involved in the
      parasympathetic drive of SPG neurons. In this study, acute isolation of adult rat
      SPG neurons was developed in order to begin the electrophysiological
      characterization of this ganglion. Under our dissociation conditions, the average
      number of neurons obtained per ganglion was greater than 1200. Immunofluorescence
      imaging results showed positive labeling with acetylcholinesterase (AChE),
      confirming the parasympathetic nature of SPG neurons. On the other hand, weak
      tyrosine hydroxylase immunostaining was observed in these neurons. Whole-cell
      patch-clamp recordings revealed that most of the Ca(2+) current is carried by N
      type (53%) and SNX-482 resistant R-type (30%) Ca(2+) channels. In addition,
      Ca(2+) currents were inhibited in a voltage-dependent manner following exposure
      to oxotremorine-M (Oxo-M), norepinephrine and ATP via muscarinic acetylcholine
      receptor 2 (M(2) AChR) subtype, adrenergic and P2Y purinergic receptors,
      respectively. The peptides VIP and angiotensin II failed to modulate Ca(2+)
      currents, suggesting that these receptors are not present on the SPG soma or do
      not couple to Ca(2+) channels. In summary, our data suggest that the Ca(2+)
      current inhibition mediated by Oxo-M, NE and ATP in adult rat SPG neurons plays
      an integral part in maintaining parasympathetic control of cranial functions.

PMID- 17507163
TI  - A randomized controlled trial of perioperative administration of pregabalin for
      pain after laparoscopic hysterectomy.
AB  - Pregabalin has anticonvulsant, antihyperalgesic, and anxiolytic properties. In
      this study we evaluated the control of pain after perioperative administration of
      pregabalin 300 or 600 mg, compared with diazepam 10mg. Altogether 91 women
      scheduled for laparoscopic hysterectomy were randomized to receive diazepam 10mg
      (D10), pregabalin 150 mg (P300) or 300 mg (P600) for premedication, and the dose
      was repeated after 12h, except for the D10 group, in which the patients received
      placebo. Up until the 1st postoperative morning, analgesia was provided by
      oxycodone using patient controlled analgesia. The visual analogue scale scores
      for pain and side effects, and the amounts of the analgesics were recorded for
      three days after surgery. The doses of oxycodone during hours 0-12 after surgery
      were similar in the three groups, whereas the dose of oxycodone during hours 12
      24 after surgery was smaller in the P600 group than in the P300 group (0.09 vs.
      0.16 mg kg(-1); P=0.025). The total dose of oxycodone (0-24h after surgery) was
      smaller in the P600 group than in the D10 group (0.34 vs. 0.45 mg kg(-1);
      P=0.046). The incidence of dizziness (70% vs. 35%; P=0.012), blurred vision (63%
      vs. 14%; P=0.002) and headache (31% vs. 7%; P=0.041) were higher in the P600
      group than in the D10 group. In conclusion, perioperative administration of
      pregabalin 600 mg decreases oxycodone consumption compared with diazepam 10mg,
      but is associated with an increased incidence of adverse effects.

PMID- 17507164
TI  - The role of pro-inflammatory cytokines in cancer treatment-induced alimentary
      tract mucositis: pathobiology, animal models and cytotoxic drugs.
AB  - Alimentary tract (AT) mucositis can be a major problem for patients undergoing
      cancer treatment. It has significant clinical and economic consequences and is a
      major factor that can compromise the provision of optimal treatment for patients.
      The pathobiology of AT mucositis is complex and the exact mechanisms that
      underlie its development still need to be fully elucidated. Current opinion
      considers that there is a prominent interplay between all of the compartments of
      the mucosa involving, at a molecular level, the activation of transcription
      factors, particularly nuclear factor-kappaB, and the subsequent upregulation of
      pro-inflammatory cytokines and inflammatory mediators. The purpose of this review
      is to examine the literature relating to what is currently known about the
      pathobiology of AT mucositis, particularly with respect to the involvement of pro
      inflammatory cytokines, as well as currently used animal models and the role of
      specific cytotoxic chemotherapy agents in the development of AT mucositis.

PMID- 17507166
TI  - Biomechanical and electromyogram characterization of neuroleptic-induced rigidity
      in the rat.
AB  - Rodent models of Parkinson's disease (PD) are usually assessed using measures of
      akinesia, but other important parkinsonian symptoms such as rigidity are only
      rarely quantified. This is in part due to technical difficulties in obtaining
      such measures in small animals. In the present study we developed quantitative
      methods to provide time-course assessment of the alternations of muscle tone of
      parkinsonian rats. A portable and miniature biomechanical stretching device was
      established to manually stretch the hindlimb of awake rats with muscle rigidity
      induced by dopamine D2-receptor antagonist raclopride (5 mg/kg, i.p.). From the
      measured angular displacement angle and reactive torque of sinusoidal stretches
      at five varied frequencies, viscoelastic components of the muscle tone can be
      derived. In addition, non-invasive multielectrode was applied to record the tonic
      and phasic components of the gastrocnemius muscle electromyogram (EMG). Our
      biomechanical measurements showed not only increase in stiffness (P<0.05) but
      also increase in viscous components (P<0.05) that matched the time course of
      increased amplitude of EMG activity (P<0.05). There was a significant positive
      correlation between all of these measures and akinesia, as measured by the
      conventional bar-test for catalepsy (with a correlation coefficient of 0.87 at
      stiffness, 0.92 at viscosity and 0.96 at amplitude of EMG). Phasic contraction
      counts (PCC) of voluntary EMG exhibited a significantly negative correlation with
      the bar test scores (correlation coefficient=-0.78). These results confirm that
      akinesia induced by D2-receptor blockade also induces a rigidity that shares many
      features with human PD. These novel techniques for quantifying biomechanical and
      electromyographic parameters provide objective assessment methods for
      investigating the time-course changes of abnormal muscle tone in rat models of PD
      that will be useful for evaluating novel treatments.

PMID- 17507165
TI  - Selective anterograde tracing of the individual serotonergic and nonserotonergic
      components of the dorsal raphe nucleus projection to the vestibular nuclei.
AB  - It is well known that the dorsal raphe nucleus (DRN) sends serotonergic and
      nonserotonergic projections to target regions in the brain stem and forebrain,
      including the vestibular nuclei. Although retrograde tracing studies have
      reported consistently that there are differences in the relative innervation of
      different target regions by serotonergic and nonserotonergic DRN neurons, the
      relative termination patterns of these two projections have not been compared
      using anterograde tracing methods. The object of the present investigation was to
      trace anterogradely the individual serotonergic and nonserotonergic components of
      the projection from DRN to the vestibular nuclei in rats. To trace
      nonserotonergic DRN projections, animals were pretreated with the serotonergic
      neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), and then, after 7 days, the
      anterograde tracer biotinylated dextran amine (BDA) was iontophoretically
      injected into the DRN. In animals treated with 5,7-DHT, nonserotonergic BDA
      labeled fibers were found to descend exclusively within the ventricular plexus
      and to terminate predominantly within the periventricular aspect of the
      vestibular nuclei. Serotonergic DRN projections were traced by injecting 5,7-DHT
      directly into DRN, and amino-cupric-silver staining was used to visualize the
      resulting pattern of terminal degeneration. Eighteen hours after microinjection
      of 5,7-DHT into the DRN, fine-caliber degenerating serotonergic terminals were
      found within the region of the medial vestibular nucleus (MVN) that borders the
      fourth ventricle, and a mixture of fine- and heavier-caliber degenerating
      serotonergic terminals was located further laterally within the vestibular
      nuclear complex. These findings indicate that fine-caliber projections from
      serotonergic and nonserotonergic DRN neurons primarily innervate the
      periventricular regions of MVN, whereas heavier-caliber projections from
      serotonergic DRN neurons innervate terminal fields located in more lateral
      regions of the vestibular nuclei. Thus, serotonergic and nonserotonergic DRN
      axons target distinct but partially overlapping terminal fields within the
      vestibular nuclear complex, raising the possibility that these two DRN projection
      systems are organized in a manner that permits regionally-specialized regulation
      of processing within the vestibular nuclei.

PMID- 17507167
TI  - Role of reactive oxygen species in modulation of Nrf2 following ischemic
      reperfusion injury.
AB  - The transcriptional factor Nrf2 has a unique role in various physiological stress
      conditions, but its contribution to ischemia/reperfusion injury has not been
      fully explored. Therefore, wildtype (WT) and Nrf2 knockout (Nrf2(-/-)) mice were
      subjected to 90-min occlusion of the middle cerebral artery (MCA) followed by 24
      h reperfusion to elucidate Nrf2 contribution in protecting against
      ischemia/reperfusion injury. Infarct volume, represented as percent of
      hemispheric volume, was significantly (P<0.05) larger in Nrf2(-/-) mice than in
      WT mice (30.8+/-6.1 vs. 17.0+/-5.1%). Furthermore, neurological deficit was
      significantly greater in the Nrf2(-/-) mice. To examine whether neuronal
      protection was mediated by Nrf2, neurons were treated with various compounds to
      induce excitotoxic or oxidative stress. Translocation of Nrf2 into the nucleus
      was increased by the free-radical donor tert-butylhydroperoxide, but not by
      glutamate or N-methyl-D-aspartic acid (NMDA). In addition, a common Nrf2 inducer,
      tert-butylhydroquinone, significantly attenuated neuronal cell death induced by
      tert-butylhydroperoxide (83.6+/-1.6 vs. 62.0+/-7.7%) but not as substantially
      when excitotoxicity was induced by NMDA (91.9+/-1.6 vs. 79.3+/-3.3%) or glutamate
      (87.8+/-1.5 vs. 80.2+/-2.6%). The results suggest that Nrf2 reduces ischemic
      brain injury by protecting against oxidative stress.

PMID- 17507168
TI  - L-type calcium channel blockade modifies anesthetic actions on aged hippocampal
      neurons.
AB  - Previous studies in our laboratory demonstrated a reversal of anesthetic actions
      on aged neurons by decreasing extracellular [Ca(2+)] in hippocampal slices. Such
      maneuver indirectly attenuated Ca(2+) influx, hence decreased exogenous
      intraneuronal Ca(2+) loads during neuronal activity and consequently improved
      intracellular Ca(2+) concentration homeostasis. Therefore, in the present study
      we hypothesized that decreasing exogenous Ca(2+) loads by blocking voltage-gated
      calcium influx in aged neurons would oppose isoflurane actions. Conversely,
      increasing endogenous Ca(2+) loads by suppressing calcium efflux during forced
      reversal of Na(+)/Ca(2+) exchanger function would enhance anesthetic effects.
      Hippocampal slices were prepared from young (2-4 months) and old (24-26 months)
      Fischer 344 rats. Isoflurane depressed the evoked dendritic field excitatory
      postsynaptic potentials by approximately 45% in slices taken from old animals.
      However, application of isoflurane in addition with CoCl(2) or nifedipine opposed
      the anesthetic actions, which then depressed the evoked dendritic field
      postsynaptic potentials by only 15%. Selective blockade of the N-type and P/Q
      type calcium channels with omega-conotoxin GVIA and omega-conotoxin MVIIC
      respectively caused rapid but partial depression of synaptic transmission in
      slices taken from old Fischer 344 rats. However, isoflurane actions in these aged
      slices were not affected compared with slices perfused only with normal
      artificial cerebrospinal fluid. Young and aged slices were then exposed to a low
      sodium perfusate that forces the Na(+)/Ca(2+) exchanger protein into a reverse
      mode, thus increasing intracellular Ca(2+) concentration. Isoflurane actions
      under such conditions were profoundly potentiated in aged slices but were not
      altered in young hippocampi. The current results show that in aged central
      neurons, selectively blocking L-type calcium channels opposes anesthetic-induced
      depression of excitatory synaptic transmission. On the contrary, increasing
      calcium loads in aged neurons potentiates these actions.

PMID- 17507170
TI  - Anti-glutamatergic effect of riluzole: comparison with valproic acid.
AB  - Riluzole, an anti-amyotrophic lateral sclerosis drug, known to decrease
      presynaptic glutamate release, is viewed as a candidate supplementary medication
      for epilepsy. In the present study, we compared the effects of riluzole and
      valproate (VPA) in the pilocarpine-induced limbic seizure model and in the gamma
      hydroxybutyrate lactone (GBL)-induced absence seizure model. We applied
      immunohistochemical study for vesicular transporter 1 (VGLUT1) and extracellular
      recording in the rat dentate gyrus of both pilocarpine- and GBL-induced seizure
      models to measure effects of riluzole and VPA. Both VPA and riluzole treatments
      reduced VGLUT1 immunoreactivity. Riluzole treatment completely inhibited pre
      ictal spikes and spike-wave discharges in the pilocarpine- and GBL-induced
      epilepsy models, whereas VPA partially inhibited these phenomena. In both seizure
      models, the anti-epileptic effects of VPA and riluzole are basically related to
      anti-glutamatergic (reducing field excitatory postsynaptic potential slope and
      excitability ratio), not GABAergic (paired-pulse inhibition) effect. Riluzole was
      more effective at reducing seizure activity in both epilepsy models than VPA.
      These results suggest that riluzole is a potential antiepileptic drug with
      activity against limbic seizure and absence seizure.

PMID- 17507169
TI  - Cannabinoid CB1 receptors in the paraventricular nucleus and central control of
      penile erection: immunocytochemistry, autoradiography and behavioral studies.
AB  - [N-(piperidin-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide] (SR
      141716A), a selective cannabinoid CB1 receptor antagonist, injected into the
      paraventricular nucleus of the hypothalamus (PVN) of male rats, induces penile
      erection. This effect is mediated by the release of glutamic acid, which in turn
      activates central oxytocinergic neurons mediating penile erection. Double
      immunofluorescence studies with selective antibodies against CB1 receptors,
      glutamic acid transporters (vesicular glutamate transporters 1 and 2 (VGlut1 and
      VGlut2), glutamic acid decarboxylase-67 (GAD67) and oxytocin itself, have shown
      that CB1 receptors in the PVN are located mainly in GABAergic terminals and
      fibers surrounding oxytocinergic cell bodies. As GABAergic synapses in the PVN
      impinge directly on oxytocinergic neurons or on excitatory glutamatergic
      synapses, which also impinge on oxytocinergic neurons, these results suggest that
      the blockade of CB1 receptors decreases GABA release in the PVN, increasing in
      turn glutamatergic neurotransmission to activate oxytocinergic neurons mediating
      penile erection. Autoradiography studies with [(3)H](-)-CP 55,940 show that
      chronic treatment with SR 141716A for 15 days twice daily (1 mg/kg i.p.)
      significantly increases the density of CB1 receptors in the PVN. This increase
      occurs concomitantly with an almost twofold increase in the pro-erectile effect
      of SR 141716A injected into the PVN as compared with control rats. The present
      findings confirm that PVN CB1 receptors, localized mainly in GABAergic synapses
      that control in an inhibitory fashion excitatory synapses, exert an inhibitory
      control on penile erection, demonstrating for the first time that chronic
      blockade of CB1 receptors by SR 141716A increases the density of these receptors
      in the PVN. This increase is related to an enhanced pro-erectile effect of SR
      141716A, which is still present 3 days after the end of the chronic treatment.

PMID- 17507171
TI  - The function of intersegmental connections in determining temporal
      characteristics of the spinal cord rhythmic output.
AB  - Recent renewed interest in the study of rhythmic behaviors and pattern-generating
      circuits has been inspired by the currently well-established role of oscillating
      neuronal networks in all aspects of the function of our nervous system: from
      sensory integration to central processing, and of course motor control. An
      integrative rather than reductionist approach in the study of pattern-generating
      circuits is in accordance with current developments. The lamprey spinal cord, a
      relatively simple and much-studied preparation, is a useful model for such a
      study. It is an example of a chain of coupled oscillatory units that is
      characterized by its ability to demonstrate robust coordinated rhythmic output
      when isolated in vitro. The preparation allows maximum control over the chemical
      (neuromodulators and hormones) as well as neuronal environment (sensory and
      descending inputs) of the single oscillatory unit: the pattern-generating
      circuit. The current study made use of recently developed tools for nonlinear
      analysis of time-series, specifically neurophysiological signals. These tools
      allow us to reveal and characterize biological-functional complexity and
      information capacity of the neuronal output recorded from the lamprey model
      network. We focused on the importance of different types of inputs to an
      oscillatory network and their effect on the network's functional output. We show
      that the basic circuit, when isolated from short- and long-range neuronal inputs,
      demonstrates its full potential of information capacity: maximal variation
      quantities and elevated functional complexity. Morphological and functional
      constraints result in the network exhibiting only a limited range of the above.
      This constitutes an important substrate for plasticity in neuronal network
      function.

PMID- 17507172
TI  - The psychometric utility of two self-report measures of PTSD among women
      substance users.
AB  - Given the high rates of posttraumatic stress disorder (PTSD) among substance
      users, integrated programs that target PTSD and substance use are recommended as
      best practice. To effectively implement such treatments, accurate and reliable
      PTSD screening instruments are needed. Unfortunately, no standardized PTSD
      measure has been validated among women substance abusers. Therefore, the goal of
      this investigation was to examine the psychometric utility of two PTSD measures
      to optimize the number of women clients correctly identified as meeting
      diagnostic criterion for PTSD. Forty-four women in residential substance use
      treatment were administered diagnostic interviews for PTSD (Clinician
      Administered PTSD Scale) and then completed questionnaires regarding trauma
      exposure and related symptoms. In this group, 38.6% of the participants met
      diagnostic criteria for current PTSD. A score of 38 and above on the PTSD
      Checklist Civilian Version and a Penn Inventory score of 25 and above optimally
      maximized the number of women with PTSD identified and minimized false negative
      and false positive rates.

PMID- 17507173
TI  - Are all drug addicts impulsive? Effects of antisociality and extent of multidrug
      use on cognitive and motor impulsivity.
AB  - The purpose of this investigation was to examine the influence of antisociality
      and extent of multidrug use on cognitive and motor impulsivity among substance
      dependent individuals (SDIs) that used primarily cocaine and/or heroin. One
      hundred currently abstinent male SDIs participated in the study. Extent of
      multidrug use and degree of antisociality, assessed with the Socialization Scale
      of the California Psychological Inventory (So-CPI), were used to classify
      participants into one of four groups: high antisocial/low multidrug use, high
      antisocial/high multidrug use, low antisocial/low multidrug use, and low
      antisocial/high multidrug use. All subjects completed the Iowa Gambling Task to
      assess cognitive impulsivity and the Stroop Task to measure motor impulsivity.
      Contrary to expectations, antisociality was associated with more advantageous
      performance on the Iowa Gambling Task, independent of extent of multidrug use. In
      contrast, greater multidrug use was associated with general psychomotor slowing
      on the Stroop Task. Results suggest that a subclinical form of antisociality may
      have a paradoxically facilitating effect on decision-making and cognitive
      impulsivity among SDIs.

PMID- 17507174
TI  - Exercise induced von Willebrand Factor release -- new model for routine
      endothelial testing.
AB  - Endothelial dysfunction (ED) is actively involved in the mechanism of occurrence,
      development and progression of all the degrees of atherosclerosis. The
      established impact of ED on the progress and outcome of cardiovascular diseases,
      together with convincing indications of a possible successful therapeutic
      modification, necessitate the changeover of ED assessment from experimental to a
      routine practice. As there is no appropriate method for a clinical practice,
      scientists anticipate significant research efforts in the further development.
      Among numerous methods already available, von Willebrand Factor (vWF) stands out
      significantly. In accordance with the accepted leading diagnostic role of vWF
      baseline levels in the group of peripheral endothelial markers, and earlier
      scientific observations on the absence of its expected reactivation during
      physical exercise, we hypothesised this promising theory. We believe that a
      constant stronger release of vWF in endothelial cell injury leads to the
      exhaustion of its stores in Weibel-Palade bodies with the consequent absence of
      the expected rise of concentration during the exercise. Therefore, we
      hypothesised that ED could be exhaustible vWF endothelopathy and the exercise
      induced release of vWF a new, simple, safe and reliable test for the detection of
      ED and monitoring of the expected therapeutic effect. In order to have a final
      clinical usability of the proposed diagnostic model, it is necessary to test its
      reliability in different pathological and risk states, and establish
      susceptibility in therapeutic procedures. The correlation with invasive
      functional angiographic tests and the flow mediated dilatation test of peripheral
      arteries also needs to be validated. We expect the proposed test of vWF
      inducibility to find its place in clinical practice, i.e. in prevention,
      prediction and therapy of cardiovascular diseases.

PMID- 17507175
TI  - Evolutionary, neurobiological, gene-based solution of the ideological "puzzle" of
      human altruism and cooperation.
AB  - Despite hundreds of published articles about humankind's eusocial behaviours,
      most scholars still regard the origin of human altruism and cooperation as an
      enduring puzzle, because it seems incompatible with two central tenets of
      evolution, namely, the competition between individuals and the consequent
      selective advantages of selfish traits. This "puzzle", however, rather than being
      due to insurmountable scientific difficulties, is to be attributed to two
      powerful ideologies, which are politically opposite, but nevertheless concurred
      to prevent scholars from solving it. One ideology rejects the concept of genetic
      determinism, whereas the other dislikes the concept of group selection. As a
      consequence, these widespread ideologies, which are common in the scientific
      community, too, kept scholars from realising that the puzzle of human altruism
      and cooperation can only be solved by proposing a theoretical model that is based
      precisely on both genetic determinism and group selection. This model, which was
      never advanced in published papers, is presented here. This article also proposes
      to regard ancestral environments as determinants of human eusociality. By
      contrast, virtually all previous articles about it leave primitive habitats
      unmentioned. To support the hypothesis that human unselfish behaviours represent
      genetically conserved traits that evolved ancestrally, not products of cultural
      transmission, this paper also discusses six groups of arguments in the section
      "Genes versus culture". Finally, this article advances a purely genetic
      evolutionary explanation for the uniqueness of human eusociality, thereby
      challenging prevailing cultural explanations for the incomparably developed
      levels of cooperation in humankind, which are observed in no other social
      species.

PMID- 17507176
TI  - Estimating the magnitude and field-size dependence of radiotherapy-induced
      mortality and tumor control after postoperative radiotherapy for non-small-cell
      lung cancer: calculations from clinical trials.
AB  - PURPOSE: To create, on the basis of available data, a mathematical model to
      describe the tumor stage- and field size-dependent risks/benefits of
      postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC), and to
      assess whether this simple model can accurately describe the reported changes in
      overall survival. METHODS AND MATERIALS: The increase in overall survival
      afforded by PORT is assumed equal to the increase in cancer-specific survival
      minus the rate of RT-induced mortality. The increase in cancer-specific survival
      is the product of the probabilities of (residual local disease) x (sterilization
      of residual disease with PORT) x (absence of metastatic disease). Data were
      extracted from the literature to estimate these probabilities. Different models
      were considered to relate the RT-induced mortality to field size. RESULTS: The
      rate of RT-induced mortality seems to be proportional to the cube of the field
      size. When these mortality rates are included in the model, the predicted changes
      in overall survival approximate the literature values. CONCLUSION: Clinical data
      can be explained by a simple model that suggests that RT-induced mortality is
      strongly dependent on field size and at least partly offsets the benefit afforded
      by PORT. Smaller RT fields, tailored to treat the areas most at risk for
      recurrence, provide the highest therapeutic ratio. The data used do not reflect
      the impact of chemotherapy, which will reduce the rate of distant metastases and
      enhance the efficacy of RT.

PMID- 17507177
TI  - Triterpenoids from leaves of Elaeophorbia drupifera.
AB  - A survey of the hexane extract of the leaves of Elaeophorbia drupifera led to the
      isolation of a new triterpenoid named elaeophorbate [methyl 4,4,8,10,13,14
      hexamethyl-1,17-di (prop-1-en-2-yl)hexadecahydro-1H-cyclo penta[a]phenanthrene-3
      carboxylate, 5] and eight known triterpenoids. Based on spectroscopic methods,
      coupled with high resolution gas chromatography-mass spectrometry the structures
      of all the compounds were elucidated.

PMID- 17507178
TI  - Cytotoxic activity of Origanum dictamnus.
AB  - Several extracts of Origanum dictamnus, an endemic plant of Greece growing only
      in the island of Crete and the bioassay-directed isolated ursolic acid, were
      tested in vitro against the P388 (murine leukemia) and the human bronchial
      epidermoid cancer NSCLC-N6 (non small cell lung cancer) cell lines. Both the
      initial dichloromethane extract and the isolated from it ursolic acid exhibited
      cytotoxic activity. Ursolic acid was also tested in vivo, on murine ascite
      leukemia P388, where it exhibited at a dose of 50 mg/kg a marginal antileukemic
      activity.

PMID- 17507179
TI  - Recovery of Pavlovian sign-tracking (autoshaping) following the discontinuation
      of inter-trial interval food in rats.
AB  - In pigeons, Pavlovian autoshaped keypecking produced by keylight-food pairings
      has been eliminated by introducing food during periods between CS presentations
      (i.e., during the inter-trial intervals). Keypecking eliminated in this manner
      reappears when the inter-trial USs are discontinued even though the CS is no
      longer paired with US. The present experiment investigated whether this recovery
      of responding produced by discontinuing unpaired inter-trial US presentations
      could be extended to another species, rats, within a Pavlovian sign-tracking
      paradigm. Rats were initially trained on a procedure where insertion of one
      retractable lever (CS(+)) was followed, response independently, with food, while
      insertion of another lever (CS(-)) was not paired with food. Rats quickly came to
      contact the CS(+) lever at high rates, but contacted the CS(-) lever
      infrequently. In the next phase, CS(+) was no longer followed by food. Explicitly
      unpaired food was presented only during the inter-trial intervals when both
      levers were absent. This treatment essentially eliminated the sign-tracking
      response. In the final phase, the unpaired inter-trial food presentations were
      discontinued while both CSs continued to be presented without food. This produced
      a significant recovery of the sign-tracking elicited by the CS(+) lever,
      extending the species generality of the Pavlovian resurgence phenomenon that has
      previously only been reported in pigeons, to rats.

PMID- 17507180
TI  - Respondent-driven sampling to assess characteristics and estimate the number of
      injection drug users in Bangkok, Thailand.
AB  - BACKGROUND: Since early in Thailand's HIV epidemic, HIV seroprevalence among
      injection drug users (IDUs) in Bangkok has been around 40%. As Thailand moves to
      strengthen HIV prevention and care programs for Bangkok IDUs, information on
      current patterns of drug use and an estimate of the size and composition of the
      IDU population are essential. METHODS: We used respondent-driven sampling (RDS)
      to recruit Bangkok IDUs who reported injecting in the past 6 months. IDUs were
      interviewed with a standardized questionnaire. Logistic regression was used to
      compare IDUs currently or previously in treatment with those never treated. RDS
      software was used to estimate IDU population size based on the proportion in
      treatment. RESULTS: Of 963 IDUs recruited, 828 (86%) were men. One hundred and
      twelve IDUs (12%) reported never having attended a drug treatment clinic. Young
      age, unemployment, injection of single drug, and never having been HIV tested
      were significantly associated with never-in-treatment status. The estimated
      proportion of IDUs in treatment was 0.55 (95% confidence interval, 0.52-0.60).
      Dividing the known number of IDUs in treatment (1981 IDUs attending Bangkok drug
      treatment clinics during October 2003 through March 2004) by this proportion, we
      estimated the number of IDUs in Bangkok during the period of RDS to be 3595 (95%
      confidence interval, 3296-3810). CONCLUSIONS: Data obtained through RDS, although
      subject to limitations from co-existing government drug control policies and
      possible under-recruitment of out-of-treatment IDUs, will be useful in informing
      policy, strengthening prevention approaches, and improving methods to monitor the
      HIV epidemic among Thai IDUs.

PMID- 17507181
TI  - The gene expression profile of Bombyx mori silkgland.
AB  - During prepupal stage, the genes expression in silkgland is considered as a model
      for gene expression and regulation of eukaryotes. Aiming to comprehensively
      interpret gene expression profile in the silkgland, we collected all currently
      available EST, complete cDNA and protein expression information and other gene
      expression testing data published before, and explored their roles in their
      function pathways level. With the analysis of interaction between the known
      proteins and putative bio-macromolecules partners in silico, we list our
      prediction results in the form of pathway classification and test some of their
      expressions by experiments.

PMID- 17507182
TI  - Functional analysis on the 5'-flanking region of human FXR gene in HepG2 cells.
AB  - The farnesoid X receptor (FXR) is a bile acid (BA)-activated nuclear receptor
      that plays a major role in the regulation of BA and lipid metabolism. Although
      modulation of FXR expression has been reported, the mechanisms underlying the
      regulation of human FXR are yet unclear. Functional assays showed that the 
      150/+29 nucleotides region from the first nucleotide at the Exon I is the minimal
      promoter of the human FXR gene by the technique of serial deletion and point
      mutants of the 5'-flanking region. Chromatin immunoprecipitation analysis and
      electrophoretic mobility shift assay revealed that hepatic nuclear factor 1alpha
      (HNF1alpha) interacted with the region. Co-transfection of the promoter with
      HNF1alpha expression vectors enhanced promoter activity of FXR gene. Over
      expression of HNF1alpha up-regulated FXR expression in HepG2 cells. These data
      indicate that (a) the identified HNF1alpha binding site serves as a positive
      regulatory sequence, (b) the binding site is functionally active both in vivo and
      in vitro, and (c) the transcription factor HNF1alpha that binds to this site
      plays an important role in the regulation of human FXR promoter activity.

PMID- 17507183
TI  - The oncogene and developmental regulator EVI1: expression, biochemical
      properties, and biological functions.
AB  - The EVI1 gene codes for a zinc finger transcription factor with important roles
      both in normal development and in leukemogenesis. Transcriptional activation of
      this gene through chromosome rearrangements or other, yet to be identified
      mechanisms leads to particularly aggressive forms of human myeloid leukemia. In
      vitro as well as in animal model systems, EVI1 affected cellular proliferation,
      differentiation, and apoptosis in cell type specific ways. Retroviral
      integrations into the EVI1 locus provided cells with increased abilities to
      engraft, survive, and proliferate in bone marrow transplantation experiments.
      Experimental overexpression of EVI1 by itself was insufficient to cause leukemia
      in animal model systems, but it cooperated with other genes in this process. This
      review summarizes the currently available experimental evidence for the proposed
      biochemical and biological functions of this important oncogene.

PMID- 17507184
TI  - Effect of type I interferons on the expression of feline leukaemia virus.
AB  - The efficacy of interferons (IFNs), used empirically to treat retrovirus-infected
      cats has been shown in vivo, but the direct effect on infected cells is largely
      unknown. Ten-fold serial dilutions of three recombinant IFNs available for
      therapy, human IFNalpha(2a), IFNalpha(A/D) and feline IFNomega were added to the
      chronically FeLV-infected cell line FL74. IFNs did not apparently affect viral
      protein expression. However, reverse transcriptase activity (RT), directly
      proportional to the amount of infectious free virions, decreased with increasing
      concentrations of IFN and longer treatment times. The induction of apoptosis by
      IFN was suspected. Results of its evaluation by annexin V-Fluos staining showed
      that IFNs decreased the viability of treated FeLV-infected cells, and increased
      apoptosis, but not of non-infected cells. According to the IC(50),
      rHuIFNalpha(A/D) appeared to be the most effective IFN in inhibiting RT.

PMID- 17507185
TI  - Detection of central nervous system tissues in meat products: validation and
      standardization of a real-time PCR-based detection system.
AB  - Several phenotypic as well as genotypic methods have been published describing
      the detection of central nervous system (CNS) tissues that are part of the bovine
      spongiform encephalopathy (BSE) risk material in food products. However, none of
      these methods is able to differentiate between CNS tissue of the banned ruminant
      species and tissues of other animal species. A quantitative and species-specific
      real-time RT-PCR method has been developed that enables the reliable
      identification of CNS tissues in meat and meat products. This method is based on
      a messenger (m)RNA assay that uses bovine, ovine and caprine glial fibrillary
      acidic protein (GFAP) encoding gene sequences as markers. The in-house validation
      studies evaluated the tissue specificity of up to 15 bovine tissues and the
      standardization of absolute as well as relative quantitative measurement. The
      specific amplification of spinal cord and brain tissue GFAP cDNA has been shown
      previously. In addition, two commercially available ELISA kits were used for the
      comparative analysis of artificially contaminated minced meat. Small quantities
      of bovine brain that had been stored over the recommended period of 14 days were
      examined. The real-time PCR method proved to be suitable for the detection of
      0.1% CNS tissue. No false negative results were observed. The quantitative
      detection of GFAP mRNA using real-time RT-PCR seems a suitable tool in routine
      diagnostic testing that assesses the illegal use of CNS tissue in meat and meat
      products. The stability of the selected target region of the GFAP mRNA also
      allows the detection of CNS tissues after the meat has been processed.

PMID- 17507186
TI  - Potential involvement of EGF-like growth factors and phosphodiesterases in
      initiation of equine oocyte maturation.
AB  - Human chorionic gonadotropin (hCG) was administered to mares in estrus with
      large, dominant ovarian follicles to initiate follicular and oocyte maturation.
      Follicular contents were collected at 0, 2, 4 and 6 h after hCG. Epiregulin,
      amphiregulin and phosphodiesterase (PDE) mRNA contents of granulosa cells (PDE
      4D) were determined by reverse transcription and real-time PCR; PDE 3A mRNA
      content of single oocytes was determined similarly. Copy numbers of mRNA did not
      increase for PDE 3A or 4D over the time interval studied. Amounts of epiregulin
      and amphiregulin mRNA were correlated (r=0.98) when log transformed. Epiregulin
      and amphiregulin mRNA increased (P<0.01) from controls by 4 h after hCG
      administration, with amphiregulin increasing (P<0.01) by 2 h after hCG
      administration. Epiregulin and amphiregulin mRNA levels remained elevated
      (P<0.01) at 6h after hCG. These results indicate that EGF-like growth factors are
      likely paracrine mediators of the LH signal in the horse.

PMID- 17507187
TI  - Identification of putative pheromones in bovine (Bos taurus) faeces in relation
      to estrus detection.
AB  - Ten different volatile compounds were detected in bovine faeces using three
      chromatograms. The chemical profiles of estrus faeces were distinguished
      significantly from other phases by the presence of three specific substances,
      viz. acetic acid and propionic acid and 1-iodo undecane. The estrus specific
      synthetic compounds were rubbed onto the genital region of nonestrus animals
      (dummy cows), and the bulls were allowed to sniff the genital region and observed
      sexual behaviours. The statistical significance was higher (P<0.001) in bulls
      exhibiting repeated flehmen and mounting behaviours towards the mixture of acetic
      acid, propionic acid and 1-iodo undecane. The bioassay revealed that the fatty
      acids viz., acetic acid; propionic acid and 1-iodo undecane produced in faeces
      during estrus appear to be estrus specific. The results suggest that these
      compounds may be used as estrus indicator in cow, probably involved in bovine
      biocommunication.

PMID- 17507188
TI  - Involvement of insulin and growth hormone (GH) during follicular development in
      the bovine ovary.
AB  - Insulin and growth hormone (GH) play critical roles in the process of follicular
      development and maturation. However, the involvement of insulin receptor (IR) and
      GH receptor (GHR) during follicular development is not well understood. The aim
      of this study was to investigate the expression of IR and GHR mRNAs in the
      granulosa cells (GCs) and theca tissues (TCs) of the follicle at different
      developmental stages (preovulatory dominant follicles, POFs; estrogen-active
      dominant follicles, EADs; estrogen-inactive dominant follicles, EIDs; and small
      follicles, SFs), and second, to examine the effects of follicle-stimulating
      hormone (FSH) and estradiol (E2) on the expression of IR and GHR genes in
      cultured bovine GCs. Although the concentration of insulin in follicular fluid
      (FF) was constant at all developmental stages, the GH concentration in FF was
      significantly increased in the EAD and POF compared with the EID. IR mRNA in GCs
      and TCs was significantly increased in the POF compared with other follicles.
      Regarding GHR expression, significant increases of mRNA expression were observed
      in GCs of EAD compared to those of SF, EID and POF. GHR mRNA in TCs was
      significantly decreased in the SF compared with other follicles. In cultured GCs,
      FSH, but not E2, stimulated the expression of IR and GHR genes. Our results
      suggest that the increase in the expression of GHR may be a turning point for
      follicles to enter the ovulatory phase during final follicular development and
      that the insulin system may support the maturation of preovulatory follicles.

PMID- 17507189
TI  - Controlling of systemic absorption of gliclazide through incorporation into
      alginate beads.
AB  - This work investigates preparation of biodegradable beads with alginate polymer
      by ionotropic gelation method to take the advantages of the swelling and
      mucoadhesive properties of alginate beads for improving the oral delivery of the
      antidiabetic agent gliclazide. It demonstrates that the ionic gelation of
      alginate molecules offers a flexible and easily controllable process for
      manipulating the characteristics of the beads which are important in controlling
      the release rate and consequently the absorption of gliclazide from the
      gastrointestinal tract. Variations in polymer concentration, stirring speed,
      internal phase volume and the type of surfactant in the external phase were
      examined systemically for their effects on the particle size, incorporation
      efficiency and flow properties of the beads. The swelling behavior was strongly
      dependent on the polymer concentration in the formulations and the pH of the
      medium. The in vitro release experiments revealed that the swelling is the main
      parameter controlling the release rate of gliclazide from the beads. In vivo
      studies on diabetic rabbits showed that the hypoglycemic effect induced by the
      gliclazide loaded alginate beads was significantly greater and more prolonged
      than that induced by the marketed conventional gliclazide tablet (Gliclazide).
      The results clearly demonstrated the ability of the system to maintain tight
      blood glucose level and improved the patient compliance by enhancing, controlling
      and prolonging the systemic absorption of gliclazide.

PMID- 17507190
TI  - Determination of nifedipine in human plasma and its use in bioequivalence study.
AB  - A sensitive atmospheric pressure chemical ionization liquid chromatographic-mass
      spectrometric (APCI-LC-MS) assay with positive ion mode has been developed for
      the determination of nifedipine in human plasma. In this method, nifedipine was
      extracted from human plasma using diethyl ether with dimethoxanate as the
      internal standard. Analysis was achieved on a BDS C(18) column with methanol
      H(2)O (66:34, v/v) as the mobile phase. Sustained-release nifedipine tablets from
      DiSha (test, Weihai, China) and from GuoFeng (reference, Qingdao, China) were
      evaluated following a single 20mg oral dose to 20 healthy volunteers.
      Bioequivalence between the products was determined by calculating 90% confidence
      intervals (90% CI) for the ratio of C(max), AUC(0-t) and AUC(0-infinity) values
      for the test and reference products, using logarithmic transformed data. The 90%
      confidence intervals for the ratio of C(max) (86.6-105.2%), AUC(0-t) (97.8
      110.9%) and AUC(0-infinity) (96.5-110.4%) values for the test and reference
      products are within the interval (80.0-125.0% for AUC, and 70-143% for C(max)),
      proposed by State of Food and Drug Administration [SFDA, 2005. Guidance for
      Bioavailability and Bioequivalence Studies for Chemical Drug Products in Human
      Being. China, p. 19]. It was concluded that the two sustained-release nifedipine
      tablets are bioequivalent in their rate and extent of absorption and, thus, may
      be used interchangeably.

PMID- 17507191
TI  - Criminalistic identification of PGM-containing products of mining and
      metallurgical companies.
AB  - In early 1990 s some organized criminal groups started to develop a new field of
      illegal business, which involved thefts of intermediary products from mining and
      metal-producing plants in Russia and in the south of Africa. Since local sulfide
      copper/nickel ores contain certain concentrations of precious and platinum group
      metals (PGMs), the intermediary products recovered at different stages of
      metallurgical transformation of these ores are materials of high commercial
      value. Illicit transportation and refining of these materials in Western Europe
      and North America has evolved into a large-scale business, where a lot of
      unlawful revenues are being laundered. The most important tasks in combating this
      organized crime are as follows: to establish the facts when some PGM-containing
      semi-products had been received at certain refineries; to carry out the
      identification of these semi-products; and to prove that these semi-products had
      been produced by a certain company. As a rule, it is not difficult to establish
      the identity of a "clean product". However, when a material is a mix of several
      semi-products or a mix of some semi-product with masking substances, the
      identification of individual components becomes an extremely complicated task.
      The purpose of developing the "complex procedure for establishing the nature and
      source of origin of precious metal-bearing products of mining and metallurgical
      operations" was to make possible the identification of complex mixes comprised of
      various metallurgical semi-products. In the complex procedure that we have
      developed to characterize dispersed materials, distribution of particles by their
      elemental composition (the so-called "pseudophase" composition) was used instead
      of mineralogical composition. To determine the "pseudophase" composition by the
      method of scanning electron microscopy with X-ray spectral microanalysis (SEM
      EDX), a representative sample of material containing not less than 1000 particles
      was analyzed. All microparticles can be divided into several types. Each type is
      characterized by an association of chemical elements contained. The first stage
      includes the study of elemental composition by inductively coupled plasma optical
      emission spectrometry and inductively coupled plasma mass-spectrometry; and the
      study of phase composition by X-ray diffractometry. The results of each study are
      compared with data in the Data Base. In case of coincidence with one of the
      products with respect to all diagnostic features, the type of product and its
      source of origin are defined accordingly. If the features of the sample under
      analysis detected by the aforementioned methods do not coincide with any of the
      product types represented in Data Base, it is necessary to examine elemental
      composition and morphology of separate particle contained in the substance using
      SEM-EDX. If some particles characterized by features coinciding with features of
      particles belonging to any product or products from Data Base are found, this
      product or a mixture of products is assumed to be present in the composition of
      the substance under analysis. The assumption that the substance is a mixture can
      be verified by juxtaposing all previously determined features of the analyzed
      sample with the features of the pattern mixture (superposition) of the
      appropriate types of products represented in Data Base. Depending on the results
      of this verification the corresponding conclusion can be made.

PMID- 17507192
TI  - Rapidly developing leptomeningeal carcinomatosis following anterior skull base
      surgery: a case report.
AB  - Leptomeningeal carcinomatosis is rare in evolution of head and neck cancers.
      Prognosis is poor and treatment is through supportive care. We report an atypical
      rapid post-operative leptomeningeal carcinomatosis after skull base resection for
      an ethmoidal adenocarcinoma. The anterior skull base resection was near-total and
      we suspect a seeding of subarachnoid space either before surgery, either during
      surgical extirpation or from the residual intracranial nodule. It is the first
      description of rapid LMC after surgery (less than 1 month). Post-operative MRI
      diagnosed the LMC through the detection of contrast enhancing leptomeningeal
      nodules at bilateral second and eighth cranial nerves and at bilateral
      interpedoncular area. A strong index of suspicion along with clinical and
      radiological correlation is essential to arrive at a correct diagnosis.
      Otolaryngologists should be aware of the possibility of leptomeningeal
      carcinomatosis, before or after surgery, in a patient presents with an
      appropriate constellation of neurologic symptoms and a history of cancer.

PMID- 17507193
TI  - Outcome after corpus callosotomy in children with injurious drop attacks and
      severe mental retardation.
AB  - Wide variability in patient selection, extent of callosal section and definition
      of successful outcome between studies make impact of corpus callosotomy on
      patients with medically refractory epilepsies difficult to interpret. Severe
      mental retardation is considered to be predictive of unfavorable seizure outcome
      after callosotomy. Very little attention has been paid on the influence of
      callosotomy on the psychosocial burden on the patients' families. We evaluated
      the seizure outcome, and parental perception about change in cognition and
      behavior of 17 children (median age 9.5 years, range 3.5-18 years) with severe
      mental retardation (IQ<30 in all, except one) and injurious drop attacks, who
      have completed >or=1-year postoperative follow-up after callosotomy. Nearly two
      thirds of our patients had >or=90% reduction in drop attacks and generalized
      tonic-clonic seizures. In the one-stage total callosotomy group, 9 of 11 (82%)
      patients had favorable outcome, compared to 2 of the 6 (33%) in the partial
      callosotomy group. Absence of generalized epileptiform discharges on the 1-year
      postoperative EEG was significantly associated with a favorable seizure outcome.
      The mean duration of epilepsy prior to callosotomy tended to be shorter among
      patients with favorable seizure outcome. Postoperative complications were trivial
      and transient. Nearly three-fourths of the parents appreciated improvements in
      behavior and attentiveness of their children and were satisfied with the outcome.
      We conclude that, in children with severe mental retardation and injurious drop
      attacks, total callosotomy can be undertaken as a one-stage procedure with
      insignificant morbidity and results in highly favorable seizure outcome.

PMID- 17507195
TI  - In vitro cytotoxicity and phototoxicity of N-piperazinyl quinolone derivatives
      with a 2-thienyl group.
AB  - We examined the cytotoxic potential of nine N-[2-substituted-2-(2-thienyl)ethyl]
      piperazinyl quinolone derivatives on human oral epithelial mouth carcinoma (KB)
      and human squamous carcinoma (A431) cell lines. Phototoxic properties of these
      compounds were also evaluated by mouse 3T3 fibroblast under ultraviolet-A (UVA)
      irradiation. The percent of cell viability was evaluated by MTT assay. Compound 6
      having a 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] group attached to N4
      position of piperazine ring of enoxacin showed the highest cytotoxicity potential
      on both A431 and KB cell lines (IC50 of 3.11+/-0.52 and 4.91+/-1.94 microg/ml,
      respectively). While some of the other tested compounds exhibited clear
      phototoxic potential in 3T3 cell line, compound 6 showed only a minor potential
      of phototoxicity. These findings suggest the high potential of 4-[2
      (phenylmethoxyimino)-2-(2-thienyl)ethyl] derivative of enoxacin as a cytotoxic
      compound with low potency of phototoxic reactions. The mentioned chemical was
      identified to be of special interest for further characterization.

PMID- 17507196
TI  - Differentiation of neonatal rat epithelial cells from biliary origin into
      immature hepatic cells by sequential exposure to hepatogenic cytokines and growth
      factors reflecting liver development.
AB  - It was investigated whether cryopreserved rat liver epithelial cells (RLEC) from
      biliary origin are capable of undergoing hepatic differentiation upon sequential
      exposure to liver-specific factors (fibroblast growth factor (FGF)-4, hepatocyte
      growth factor (HGF), insulin-transferrin-sodium-selenite (ITS), dexamethasone
      (Dex) and oncostatin M (OSM)), reflecting liver embryogenesis in vivo. As
      differentiation progressed, cells acquired a hepatic morphology (polygonal-to
      cuboidal shaped, binucleated cells), corresponding well with the phenotypic
      changes observed. Biliary cytokeratin (CK)19 and connexin (Cx)43-expression both
      gradually decreased; CK19-expression disappeared even completely. In contrast,
      hepatic CK18-expression persisted throughout the culture time. Hepatocyte nuclear
      factor (HNF)3beta, alpha-foetoprotein (AFP), transthyretin (TTR), HNF4, albumin
      (ALB), HNF1alpha, multidrug resistance protein (MRP)2 and Cx32 were expressed at
      specific stages during RLEC-differentiation, thereby showing a progressive
      hepatic maturation. Indeed, immature AFP and mature ALB were sequentially
      expressed, in line with the in vivo liver embryogenesis. Expression of the early
      and mid-late 'liver-enriched' transcription factors (LETF) HNF3beta and HNF4
      declined and translocated to the cytosol, respectively, while the late LETF
      HNF1alpha underwent a nuclear upregulation. In conclusion, RLEC are bipotent
      cells, capable of differentiation into immature hepatocytes in a hepatic
      stimulating micro-environment. The robustness of the sequential conditions,
      developed before for hepatic 'transdifferentiation' of rat bone marrow stem cells
      (rBMSC), was hereby confirmed.

PMID- 17507194
TI  - Aging in adipocytes: potential impact of inherent, depot-specific mechanisms.
AB  - Fat mass and tissue distribution change dramatically throughout life. Fat depot
      sizes reach a peak by middle or early old age, followed by a substantial decline,
      together with fat tissue dysfunction and redistribution in advanced old age.
      These changes are associated with health complications, including type 2
      diabetes, atherosclerosis, dyslipidemia, thermal dysregulation, and skin ulcers,
      particularly in advanced old age. Fat tissue growth occurs through increases in
      size and number of fat cells. Fat cells turn over throughout the lifespan, with
      new fat cells developing from preadipocytes, which are of mesenchymal origin. The
      pool of preadipocytes comprises 15-50% of the cells in fat tissue. Since fat
      tissue turns over throughout life, characteristics of these cells very likely
      have a significant impact on fat tissue growth, plasticity, function, and
      distribution. The aims of this review are to highlight recent findings regarding
      changes in preadipocyte cell dynamics and function with aging, and to consider
      how inherent characteristics of these cells potentially contribute to age- and
      depot-dependent changes in fat tissue development and function.

PMID- 17507197
TI  - Bensultap decreases neuronal excitability in molluscan and mammalian central
      nervous system.
AB  - Electrophysiological experiments were performed on in vitro neuronal preparations
      from terrestrial snail and rat brain slices, to determine the effect of the
      insecticide bensultap. Although bensultap has low toxicity in mammals, our
      results showed that bensultap altered the synaptic transmission in the vertebrate
      as well as in the invertebrate central nervous system. Bensultap caused a
      significant decrease of the ACh-induced current. The effect depended on the
      preapplication time and the concentration of the chemical. Bensultap also had an
      effect on the kinetic parameters of the ACh-induced current; the desensitization
      time was altered in a concentration-dependent manner. In the rat brain slice
      preparations, we observed an increase in the amplitude of the evoked responses
      after a 30 min treatment. There was no effect on paired-pulse depression, but LTP
      induction was significantly inhibited by bensultap. The efficacy of synaptic
      transmission was modified by bensultap through effects on both input integration
      and output organization.

PMID- 17507198
TI  - Identifying students faking ADHD: Preliminary findings and strategies for
      detection.
AB  - When conducting psychological evaluations, clinicians typically assume that the
      subject being evaluated is putting forth maximal effort and is not exaggerating
      or magnifying symptom complaints. While the field of neuropsychology has
      identified that factors, such as effort and motivation, can significantly
      interfere with correct interpretation of self-reported symptoms and test scores,
      evaluation methods for other psychological conditions, such as attention deficit
      hyperactivity disorder (ADHD) have not addressed effort and motivation as
      potential factors influencing accurate diagnosis. In analyzing the performance of
      students simulating ADHD, and comparing it to performance of both non-ADHD and
      genuine ADHD students, this study clearly demonstrated that the symptoms of ADHD
      are easily fabricated, and that simulators would be indistinguishable from those
      with true ADHD. In addition, students motivated to feign ADHD could easily
      perform poorly on tests of reading and processing speed, thus allowing them
      access to academic accommodations. Implications of these findings are discussed.

PMID- 17507199
TI  - The effect of effort on baseline neuropsychological test scores in high school
      football athletes.
AB  - OBJECTIVE: Poor effort on baseline neuropsychological tests is expected to
      influence interpretation of post-concussion assessment scores. Our study examined
      effort in an athletic population to determine if poor effort effects
      neuropsychological test performance. METHODS: High school athletes (N=199) were
      administered a brief neuropsychological test battery, which included the Dot
      Counting Test (DCT) and the Rey 15-Item Test with recognition trial. One-way
      analyses of variance were used to compare groups with adequate and poor effort
      test performance. RESULTS: Most athletes (N=177; 89%) exerted adequate effort
      while a number of athletes (N=22; 11%) exerted poor effort on the DCT.
      Statistically significant differences existed between effort groups (p<0.05) on
      several of the neuropsychological tests. CONCLUSIONS: Poor effort was observed in
      the athletic population during baseline testing and athletes with poor effort
      displayed statistically significant differences in performance on
      neuropsychological tests. Adding an effort test to baseline examinations may
      improve post-concussion test score interpretations.

PMID- 17507200
TI  - Protein metabolism in adult patients with phenylketonuria.
AB  - OBJECTIVE: Protein intake recommendations in phenylketonuria (PKU) are frequently
      the subject of discussion. For healthy adults, the recommended daily allowance
      (RDA) is 0.8 g.kg(-1).d(-1), which is generally lower than that observed in the
      general Western population. We investigated whether whole-body protein metabolism
      in patients with PKU is comparable to that of healthy controls at a RDA rate of
      protein intake. METHODS: Six adult patients with well-controlled PKU and six
      healthy subjects of comparable age, height, and weight were studied using a
      primed continuous infusion of [1-(13)C]-valine for 8 h after an overnight fast
      before and during frequent meals. Normal protein was given to controls, whereas
      patients with PKU received a combination of an amino acid mixture and natural
      protein. RESULTS: No significant differences were observed between patients with
      PKU and controls in preprandial and prandial rates of valine appearance and
      oxidation and protein breakdown, protein synthesis, and net protein balance.
      Feeding resulted in a significant (P < 0.01) decrease in protein breakdown (PKU:
      94 +/- 15 micromol.kg(-1).h(-1) preprandial to 49 +/- 10 micromol.kg(-1).h(-1)
      prandial; controls: 97 +/- 10 micromol.kg(-1).h(-1) preprandial to 55 +/- 10
      micromol.kg(-1).h(-1) prandial), whereas no effects were observed in protein
      synthesis (PKU: 77 +/- 10 micromol.kg(-1).h(-1) preprandial to 73 +/- 7
      micromol.kg(-1).h(-1) prandial; controls: 76 +/- 8 micromol.kg(-1).h(-1)
      preprandial to 71 +/- 5 micromol.kg(-1).h(-1) prandial). Net protein balance
      increased from negative prandial to positive preprandial values (PKU: -17 +/- 6
      micromol.kg(-1).h(-1) preprandial to +23 +/- 8 micromol.kg(-1).h(-1) prandial;
      controls: -21 +/- 4 micromol.kg(-1).h(-1) preprandial to +16 +/- 9 micromol.kg(
      1).h(-1) prandial). CONCLUSION: Whole-body protein metabolism in adult patients
      with PKU is fully comparable to that in healthy controls at the RDA level of
      protein intake.

PMID- 17507201
TI  - A clinically applicable reporting system for the diagnosis of facial fractures.
AB  - A clinically applicable, comprehensive reporting system for the diagnosis of
      facial fractures was developed with three guiding principles: (1) preservation of
      classical anatomical terminology and nomenclature, (2) facilitation of uniform
      interpretation of radiographs between radiologists and (3) non-redundant
      diagnostic descriptions of complex fractures, in a manner that correlates with
      treatment modality. Twenty-two fracture types (17 simple fracture types and 5
      complex fracture types) are included in the system. Each patient's fracture
      pattern is described by listing the component fractures present. A short
      narrative (modifying description) is provided after each fracture listed. Simple
      fractures that help to comprise more complex fractures are not listed separately,
      but are described within the modifying description of the complex fracture they
      help to comprise. When components of multiple complex fractures are present, a
      hierarchy of complex fractures dictates which fracture is described first.
      Additional complex fractures are only described separately when they do not share
      common components. In all other cases, the second (lower order) complex fracture
      is best described by simply listing the component (simple or complex) fractures
      that are not accounted for in the higher order complex fracture. Adoption of this
      reporting system should improve communication between emergency medicine
      physicians, radiologists and surgeons.

PMID- 17507202
TI  - Patients with a sodium channel alpha 1 gene mutation show wide phenotypic
      variation.
AB  - We investigated the roles of mutations in voltage-gated sodium channel alpha 1
      subunit gene (SCN1A) in epilepsies and psychiatric disorders. The SCN1A gene was
      screened for mutations in three unrelated Japanese families with generalized
      epilepsy with febrile seizure plus (GEFS+), febrile seizure with myoclonic
      seizures, or intractable childhood epilepsy with generalized tonic-clonic
      seizures (ICEGTC). In the family with GEFS+, one individual was affected with
      panic disorder and seizures, and another individual was diagnosed with Asperger
      syndrome and seizures. The novel mutation V1366I was found in all probands and
      patients with psychiatric disorders of the three families. These results suggest
      that SCN1A mutations may confer susceptibility to psychiatric disorders in
      addition to variable epileptic seizures. Unidentified modifiers may play critical
      roles in determining the ultimate phenotype of patients with sodium channel
      mutations.

PMID- 17507203
TI  - Visual self-recognition in patients with schizophrenia.
AB  - Self-processing is associated with distinct patterns of behavior and neural
      activity in healthy individuals. Self-monitoring deficits have been reported in
      schizophrenia in auditory and tactile modalities but it is unknown whether they
      generalize to all sensory domains. We investigated self-face recognition in
      patients with schizophrenia, using a visual search paradigm with three types of
      targets: objects, famous faces and self-faces. Schizophrenic patients showed
      increased reaction time (RT) for detecting targets overall compared to normal
      controls but they showed faster RT for self-face compared with the Famous-face
      condition. For healthy controls, there was no difference between Self- and Famous
      face conditions. Thus, visual search for self-face is more efficient than for
      famous faces and self-face recognition is spared in schizophrenia. These findings
      suggest that impaired self-processing in schizophrenia may be task-dependent
      rather than ubiquitous.

PMID- 17507204
TI  - Food-dependent exercise-induced anaphylaxis.
AB  - Food-dependent exercise induced anaphylaxis (FDEIA) is a distinct form of food
      allergy induced by physical exercise. Symptoms are typically generalized
      urticaria and severe allergic reactions such as shock or hypotension. Whereas
      various food items are responsible for the development of FDEIA, wheat is
      reported to be the allergen with the highest frequency in Japan. Recently aspirin
      has been known to be an additional exacerbating factor. Skin tests and in vitro
      serum food-specific IgE assays are currently used, however their sensitivity and
      specificity are not always satisfactory. A challenge test consisting of ingestion
      of assumed food followed by intense physical exercise is the only reliable method
      to determine the causative food and to diagnose the disease. The challenge test
      is not always safe because in some cases the test induces an anaphylactic shock.
      So a reliable in vitro diagnostic method is necessary for the patients with
      FDEIA. We revealed that wheat omega-5 gliadin and high molecular weight glutenin
      subunit are major allergens in wheat-dependent exercise-induced anaphylaxis
      (WDEIA). A simultaneous detection of specific IgE to epitope sequences of both
      omega-5 gliadin and high molecular weight glutenin is found to achieve higher
      sensitivity and specificity compared with the in vitro serum food-specific IgE
      assays currently used for diagnosis of WDEIA. On the other hand, immunoreactive
      gliadins appeared in the sera of patients during the provocation test with both
      wheat-exercise and wheat-aspirin challenges in parallel with allergic symptoms.
      These findings suggest that FDEIA is IgE-mediated hypersensitivity reaction to
      foods and both exercise and aspirin facilitate allergen absorption from the
      gastrointestinal tract.

PMID- 17507206
TI  - The problem with glycopeptides.

PMID- 17507205
TI  - Experimental tissue regeneration by DDS technology of bio-signaling molecules.
AB  - The medical therapy of tissue regeneration achieved by biomaterial-based tissue
      engineering has been currently expected as the third option following
      reconstructive surgery and organ transplantation. The basic idea of this
      regenerative therapy is to assist the self-healing potentials of body to induce
      the natural regeneration and repairing of defective or injured tissue. To this
      end, it is practically important to create a local environment which enables
      cells to promote their proliferation and differentiation, resulting in the
      induction of cell-based tissue regeneration. Tissue engineering is a biomedical
      technology or methodology to build up this regeneration environment by making use
      of biomaterials. Drug delivery system (DDS) is a biomaterial technology to
      enhance the in vivo biological functions of bio-signaling molecules (growth
      factors and genes) for promoted tissue regeneration. This paper overviews the
      recent status of tissue regeneration therapy based on the DDS technology of bio
      signaling molecules.

PMID- 17507207
TI  - Changes in microbial community structure and function within particle size
      fractions of a paddy soil under different long-term fertilization treatments from
      the Tai Lake region, China.
AB  - Greenhouse gas (GHG) production and emission from paddy soils impacts global
      climate change. Soil particle size fractions (PSFs) of different sizes act as
      soil microhabitats for different kinds of microbial biota with varying conditions
      of redox reactions and soil organic matter (SOC) substrates. It is crucial to
      understand the distribution of soil microbial community structure within PSFs and
      linkage to the GHG production from paddy soils of China. The change of bacterial
      and methangenic archaeal community and activity relating to CH(4) and CO(2)
      production with PSFs under different fertilizer applications was studied in this
      paper. The fertilization trial was initiated in a paddy soil from the Tai Lake
      region, Jiangsu, China with four treatments of non-fertilized (NF), fertilized
      with inorganic fertilizers only (CF), inorganic with pig manure (CFM) and
      inorganic with straw return (CFS), respectively since 1987, and the PSFs (<2
      microm, 2-20 microm, 20-200 microm, and 200-2000 microm) were separated by a low
      energy sonication dispersion procedure from undisturbed samples. Analysis of
      bacterial community within different size particles was conducted by PCR-DGGE.
      The results indicated significant variation of bacterial community structure
      within different PSFs. The methane was predominantly produced in the coarser
      fractions, while more species and higher diversity of bacteria survived in the
      size of <2 microm fractions, in which the bacterial community structure was more
      significantly affected by fertilizer application practices than in the other
      coarser fractions. Higher bacterial species richness and more diversities in the
      smallest size fractions was due to the vicinity between microbes, access to
      carbon resource outside the microaggregates, and smaller pore size as protective
      agent suitable habitats for microbes rather than high SOC. Whereas, higher CO(2),
      CH(4) production and methanogenic archaeal community in coarser fractions may be
      contributed to storage of labile organic carbon in these fractions. It indicated
      that availability of SOC in PSFs is mainly factor affected survival of
      methanogenic archaeal community structure, whereas, bacterium community
      habitation more affected by physical protection of their location in PSFs. Their
      activity greatly depended on liability of SOC access to PSFs. Fertilizer
      application caused more change of bacteria community in clay fraction and greatly
      increased bacterium and methanogen activity in coarser fractions but only a
      slight effect on methanogenic archaeal community in the particle size fractions.

PMID- 17507208
TI  - Mechanistic study on the intestinal absorption and disposition of baicalein.
AB  - The present study aims to investigate the mechanisms of intestinal absorption and
      disposition of flavonoid baicalein (B) in Caco-2 cell monolayer model,
      transporter overexpressing membrane, and cellular models. The bidirectional
      transport studies of B and its metabolite baicalein-7-glucuronide (BG) were
      conducted at various concentrations and in the absence or presence of the
      selected transporter inhibitors. To identify specific interactions of BG with ABC
      transporters, ABC transporter-ATPase assays were carried out on membrane vesicles
      prepared from Sf9 cells overexpressing human MDR1, MRP1, MRP2, MRP3 and MXR. To
      further confirm the interactions between BG and specific ABC transporters,
      inhibition of BG on the transport of substrates of specific transporters were
      evaluated using membrane vesicles overexpressing MRP1-3 and MXR, or K562MDR cells
      with overexpressing MDR1. The results showed that B could readily pass through
      Caco-2 cell monolayer, but with significant glucuronidation and sulfation. The
      extent of phase II metabolism of B during its transport was in dose-dependent
      manner. The intracellularly formed glucuronide and sulfate of B were efficiently
      extruded to both apical and basolateral sides of the Caco-2 monolayer, which were
      reduced in the presence of MRP inhibitors. Although BG was not permeable from
      apical to basolateral side, it exhibited significant efflux transport that was
      inhibited in the presence of MRPs inhibitors. Moreover, BG seemed to activate the
      ATPase activity of both MRP3 and MXR at a pharmacologically relevant
      concentration range.

PMID- 17507209
TI  - Site investigation on medical waste management practices in northern Jordan.
AB  - This study investigated the medical waste management practices used by hospitals
      in northern Jordan. A comprehensive inspection survey was conducted for all 21
      hospitals located in the study area. Field visits were conducted to provide
      information on the different medical waste management aspects. The results
      reported here focus on the level of medical waste segregation, treatment and
      disposal options practiced in the study area hospitals. The total number of beds
      in the hospitals was 2296, and the anticipated quantity of medical waste
      generated by these hospitals was about 1400 kg/day. The most frequently used
      treatment practice for solid medical waste was incineration. Of these hospitals,
      only 48% had incinerators, and none of these incinerators met the Ministry of
      Health (MoH) regulations. As for the liquid medical waste, the survey results
      indicated that 57% of surveyed hospitals were discharging it into the municipal
      sewer system, while the remaining hospitals were collecting their liquid waste in
      septic tanks. The results indicated that the medical waste generation rate ranges
      from approximately 0.5 to 2.2 kg/bed day, which is comprised of 90% of infectious
      waste and 10% sharps. The results also showed that segregation of various medical
      waste types in the hospitals has not been conducted properly. The study revealed
      the need for training and capacity building programs of all employees involved in
      the medical waste management.

PMID- 17507210
TI  - Superoxide radical sensing using a cytochrome c3 immobilized conducting polymer
      electrode.
AB  - A biosensor based on cytochrome c3 (cyt c3) has been introduced to detect and
      quantify superoxide radical (O2*-). Cyt c3, isolated from the sulfate-reducing
      bacterium (Desulfovibrio vulgaris Miyazaki F. strain), and its mutant were
      immobilized onto a conducting polymer coated electrodes by the covalent bonding
      with carbodiimide chemistry. The immobilization of cyt c3 was investigated with
      quartz crystal microbalance, electrochemical impedance spectroscopy, and cyclic
      voltammetric studies. The CVs recorded for cyt c3 and a mutant modified
      electrodes showed a quasi-reversible behavior having the formal potential of
      about -471 and -476 mV (versus Ag/AgCl), respectively, in a 0.1M phosphate buffer
      solution (pH 7.0). The modified electrodes showed the surface controlled process
      and the electron transfer rate constants (ks) were evaluated to be 0.47 and 0.51
      s(-1) for cyt c3 and mutant modified electrodes, respectively. A potential
      application of the cyt c3 modified electrode was evaluated by monitoring the
      bioelectrocatalytic response towards the O2*-. The hydrodynamic range of 0.2-2.7
      micromole L(-1) and the detection limit of 0.05 micromole L(-1) were obtained.

PMID- 17507211
TI  - Integrated electrodes on a silicon based ion channel measurement platform.
AB  - We demonstrate the microfabrication of a low-noise silicon based device with
      integrated silver/silver chloride electrodes used for the measurement of single
      ion channel proteins. An aperture of 150 microm diameter was etched in a silicon
      substrate using a deep silicon reactive ion etcher and passivated with 30 nm of
      polytetrafluoroethylene via chemical vapor deposition. The average recorded noise
      in measurements of lipid bilayers was reduced by a factor of four through
      patterning of a 75 microm thick SU-8 layer around the aperture. Integrated
      electrodes were fabricated on both sides of the device and used for repeatable,
      stable, giga-seal bilayer formations as well as characteristic measurements of
      the transmembrane protein OmpF porin.

PMID- 17507212
TI  - Failed intubation in obstetrics.

PMID- 17507213
TI  - Treatment of molasses wastewater by acetogenic bacteria BP103 in sequencing batch
      reactor (SBR) system.
AB  - Acetogenic bacteria BP103 cells could be used as the absorbent for melanoidin
      pigment (MP) and molasses wastewater (MWW). The maximum MP adsorption yield of
      this strain observed from the dead (autoclaved) cell. It was two times higher
      than that with resting cells. However, the MP adsorption yield of the strain was
      50-60% decreased by acclimatization with the media containing MP. The
      deteriorated cells (MP-adsorbed cells) could be recovered by washing with 0.1%
      SDS, 0.1% Tween 80 and 0.1 mol/L NaOH solutions. Among them, 0.1 mol/L NaOH
      solution was most suitable according to highest elution ability and no-effect to
      the MP adsorption capacity (The adsorption yield of deteriorated cell was reduced
      only 10% after washing three times with 0.1 mol/L NaOH solution). In SBR system,
      the strain showed very low MP removal yield with both molasses wastewater (MWW)
      from the anaerobic pond (An-MWW) and stillage from an alcohol factory (U-MWW).
      However, the MP removal yield was increased by supplementation with carbon
      sources (glucose). Also, the MP removal efficiency was increased with the
      increase of supplemented-glucose concentration. The highest COD, BOD(5), TKN and
      MP removal efficiencies of the SBR system with 10 times-diluted An-MWW solution
      containing 30 g/L glucose under HRT of seven days were 65.2+/-2.5%, 82.8+/-3.4%,
      32.1+/-0.8% and 50.2+/-3.7%, respectively. The large molecular weight fraction of
      MP in both U-MWW and An-MWW solutions were rapidly removed by acetogenic bacteria
      BP103, while the small molecular weight fractions of MP still remained in the
      effluent.

PMID- 17507214
TI  - Relative changes in phosphatase activities as influenced by source and
      application rate of organic composts in field crops.
AB  - Potential impact of different levels and sources of organic composts on
      activities of phosphatases (acid and alkaline phosphatase, phosphodiesterase, and
      inorganic pyrophosphatase) was studied after three years of continuous
      application. Enzyme activities were compared with microbial biomass P and
      available P. Experimental plots were divided based on the organic source into
      three groups: those receiving farmyard manure (FYM), vermicompost (VC) and
      Lantana compost (LC). Microbial biomass P (11.7 g kg(-1) soil), available P (24.0
      g kg(-1) soil) and acid phosphatase (1.3 mg g(-1) p-NP g(-1) soil h(-1)) was
      highest in highest dose of VC. Acid phosphatase activity was high in all plots,
      including those where microbial biomass P levels were low. Most of the
      phosphatase activities were significantly correlated with available P in FYM and
      VC. These relationships were negative for LC treatments. Results showed that
      application of earthworm casts is helpful in faster transformation of organic P
      by facilitating better environment to microbes and plant roots.

PMID- 17507215
TI  - Use of high-boiling point organic solvents for pulping oil palm empty fruit
      bunches.
AB  - Oil palm empty fruit bunches were used as an alternative raw material to obtain
      cellulosic pulp. Pulping was done by using high-boiling point organic solvents of
      decreased polluting power relative to classical (Kraft, sulphite) solvents but
      affording operation at similar pressure levels. The holocellulose, alpha
      cellulose and lignin contents of oil palm empty fruit bunches (viz. 66.97%,
      47.91% and 24.45%, respectively) are similar to those of some woody raw materials
      such as pine and eucalyptus, and various non-wood materials including olive tree
      prunings, wheat straw and sunflower stalks. Pulping tests were conducted by using
      ethyleneglycol, diethyleneglycol, ethanolamine and diethanolamine under two
      different sets of operating conditions, namely: (a) a 70% solvent concentration,
      170 degrees C and 90 min; and (b) 80% solvent, 180 degrees C and 150 min. The
      solid/liquid ratio was six in both cases. The amine solvents were found to
      provide pulp with better properties than did the glycol solvents. Ethanolamine
      pulp exhibited the best viscosity and drainage index (viz. 636 mL/g and 17
      degrees SR, respectively), and paper made from it the best breaking length (1709
      m), stretch (1.95%), burst index (0.98 kN/g) and tear index (0.33 mNm(2)/g).
      Operating costs can be reduced by using milder conditions, which provide similar
      results. In any case, the amines are to be preferred to the glycols as solvents
      for this purpose.

PMID- 17507216
TI  - An ability of isolated strains to efficiently cooperate in ethanolic fermentation
      of agricultural plant refuse under initially aerobic thermophilic conditions:
      oxygen deletion process appended to consolidated bioprocessing (CBP).
AB  - For bioconversion of bean curd refuse, a processing by-product of bean curd,
      ethanol-producing anaerobic thermophiles (strains kpu03 and kpu04) were newly
      isolated. Both of them degraded hemicellulose, but not cellulose at all.
      Phylogenetically, strains kpu03 and kpu04 belong to the Clostridium and
      Thermoanaerobacterium genus, respectively. Aerobic thermophiles degrading
      cellulose were also isolated newly. Among them, strain kpuB3 particularly
      enhanced ethanol production by anaerobic strain kpu04 in the aerobic bean curd
      refuse medium. Strain kpuB3 belongs to the Geobacillus genus phylogenetically.
      The co-culture also significantly reduced CH(3)SH production, leading to the
      prevention of offensive odor. These results demonstrate that cellulolytic aerobe
      cooperated with hemicellulolytic anaerobe in ethanolic fermentation by not only
      synergistic effect but also deletion of oxygen from the vessels, providing a new
      model of oxygen deletion process appended to consolidated bioprocessing (CBP).

PMID- 17507217
TI  - Fire-retardant-treated low-formaldehyde-emission particleboard made from recycled
      wood-waste.
AB  - The objective of this study was to manufacture fire-retardant-treated low
      formaldehyde-emission particleboard from recycled wood-waste particles using
      polymeric 4,4'-methylenediphenyl isocyanate (PMDI) and phenol-formaldehyde (PF)
      resins. The influence of the PMDI/PF ratio (ratio of particles sprayed with PMDI
      to particles sprayed with PF, w/w) after fire retardant treatment on formaldehyde
      emissions, mechanical properties, and surface fire resistant performance of the
      manufactured particleboard was investigated. The experimental results showed that
      the formaldehyde emissions linearly decreased with an increasing PMDI/PF ratio.
      Moreover, the bending strength, internal bond strength, and screw holding
      strength increased with an increasing PMDI/PF ratio. The thickness swelling of
      the particleboard was improved by using an increasing PMDI/PF ratio. Furthermore,
      the fire-retardant-treated low-formaldehyde-emission particleboards fabricated in
      our study could pass the third grade standard of surface fire resistant
      performance as specified by CNS 6532.

PMID- 17507218
TI  - Alpha-methylation at benzylic fragment of N-aryl-N'-benzyl ureas provides TRPV1
      antagonists with better pharmacokinetic properties and higher efficacy in
      inflammatory pain model.
AB  - SAR studies for N-aryl-N'-benzyl urea class of TRPV1 antagonists have been
      extended to cover alpha-benzyl alkylation. Alkylated compounds showed weaker in
      vitro potencies in blocking capsaicin activation of TRPV1 receptor, but possessed
      improved pharmacokinetic properties. Further structural manipulations that
      included replacement of isoquinoline core with indazole and isolation of single
      enantiomer led to TRPV1 antagonists like (R)-16a with superior pharmacokinetic
      properties and greater potency in animal model of inflammatory pain.

PMID- 17507219
TI  - Aminosuberoyl hydroxamic acids (ASHAs): a potent new class of HDAC inhibitors.
AB  - Histone deacetylase (HDAC) inhibitors that target Class I and Class II HDACs are
      currently in advanced clinical trials for the treatment of cancer. Vorinostat
      (Zolinza, SAHA) is a hydroxamic acid approved for the treatment of patients with
      cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease
      on or following two systemic therapies. As part of an on-going effort to better
      understand the nature of the HDAC enzyme/inhibitor interaction and design highly
      effective HDAC inhibitors, we herein report the design, synthesis and HDAC
      inhibitory activity of a vorinostat-derived series of substrate-based HDAC
      inhibitors.

PMID- 17507220
TI  - Synthesis and preliminary evaluation of mono-[123I]iodohypericin monocarboxylic
      acid as a necrosis avid imaging agent.
AB  - Hypericin monocarboxylic acid was synthesized in an overall yield of 25% in four
      steps and radiolabelled with iodine-123 in good yield (>75%). The resulting mono
      [(123)I]iodohypericin monocarboxylic acid was evaluated in normal mice and in
      rats with ethanol induced liver necrosis. In this model, tracer concentration in
      necrotic liver tissue was 14 times higher than in the viable liver tissue as
      quantified by autoradiography at 24h post injection. The results indicate the
      feasibility of visualization of necrotic tissue with the novel tracer.

PMID- 17507221
TI  - Identification and SAR of potent and selective non-peptide obeline somatostatin
      sst1 receptor antagonists.
AB  - A novel class of non-peptide somatostatin receptor ligands bearing the
      octahydrobenzo[g]quinoline (obeline) structural element has been identified. SAR
      studies have been performed that led to the discovery of derivatives with high
      affinity (pK(d) r sst(1) > or = 9) and selectivity (> or = 150-fold for h sst(1)
      over h sst(2)-h sst(5)) for somatostatin receptor subtype sst(1). In a functional
      assay, the compounds act as antagonists at human recombinant sst(1) receptors.

PMID- 17507222
TI  - [1,3]Diazaheterofused isoindolol derivatives displaying anxiolytic-like effects
      on mice.
AB  - Anxiolytic-like effects induced on mice by several compounds with imidazo[2,1
      a]isoindolol (II), pyrimido[2,1-a]isoindolol (III) and [1,3]diazepino[2,1
      a]isoindolol (IV) structures have been evaluated through the elevated plus-maze
      test. The evaluation has been based on measuring the spent time and counting the
      number of entries of mice in the open arms of the maze. Single intraperitoneal
      administration of imidazoisoindolol IIe and pyrimidoisoindolols IIIa, IIIe and
      IIIg induced significant increments in these behavioural parameters.

PMID- 17507223
TI  - Synthesis and biological activity of enantiomeric pairs of 5-vinylthiolactomycin
      congeners.
AB  - Twelve enantiomeric pairs of 5-vinylthiolactomycin congeners were synthesized by
      employing our efficient synthetic route previously explored for the synthesis of
      enantiomeric pairs of thiolactomycin and its 3-demethyl derivative. From the
      biological activity assay carried out using the obtained congeners along with
      enantiomeric pairs of thiolactomycin and its 3-demethyl derivative previously
      prepared, it appeared evident that in vitro antibacterial and mammalian type I
      FAS inhibitory activity of thiolactomycin congeners can be cleanly separated by
      changing not only the structure but also the absolute configuration of the side
      chain at the C(5)-position. These studies led us to explore (S)-3-demethyl-5
      (pent-1-enyl)thiolactomycin derivative [(S)-4-hydroxy-5-methyl-5-(pent-1-enyl)-5H
      thiophen-2-one] which exhibits type I FAS inhibitory activity equal to that of
      C75, the potent inhibitor so far reported, with complete loss of in vitro
      antibacterial activity.

PMID- 17507224
TI  - Biaryl cannabinoid mimetics--synthesis and structure-activity relationship.
AB  - Synthesis, in vitro biological evaluation, and structure-activity relationships
      of a biaryl cannabinoid mimetic 2 are reported. Variations in the substitution
      pattern yielded a number of agonists with low nanomolar affinity. Replacing the
      phenol group by a methyl morpholino acetate group led to compound 28, a 500-fold
      selective CB(2) receptor agonist.

PMID- 17507225
TI  - Design, synthesis, and structure-activity relationship of carbamate-tethered aryl
      propanoic acids as novel PPARalpha/gamma dual agonists.
AB  - We have developed a new class of PPARalpha/gamma dual agonists, which show
      excellent agonistic activity in PPARalpha/gamma transactivation assay. In
      particular, (R)-9d was identified as a potent PPARalpha/gamma dual agonist with
      EC(50)s of 0.377 microM in PPARalpha and 0.136 microM in PPARgamma, respectively.
      Interestingly, the structure-activity relationship revealed that the
      stereochemistry of the identified PPARalpha/gamma dual agonists significantly
      affects their agonistic activities in PPARalpha than in PPARgamma.

PMID- 17507226
TI  - Pathological classification of ductal carcinoma in situ of the breast correlates
      with surgical treatment and may be predicted by mammography.
AB  - In order to assess the correlation of pathological and radiological features of
      ductal carcinoma in situ (DCIS) of the breast and their association with surgical
      outcome, a consecutive series of 150 patients was retrospectively examined.
      Pathological slides from all patients were divided into three categories
      according to the pathological EPWG (European Pathologist Working Group) and DIN
      (Ductal Intraepithelial Neoplasia) classifications, which showed very good inter
      correlation (r=0.99) (whole series). Mammographic images from 46 of these cases
      were blindly classified into five categories according to the level of
      radiological suspicion (R), morphology of calcifications (Ca) and preoperative
      results of needle biopsy (C/B) (limited series). No significant differences in
      the distribution of clinical and pathological variables were detected among whole
      and limited series. The lesions were grouped into two (low versus high)
      pathological (PRG), radiological (RRG and CaRG) and needle biopsy (C/BRG) risk
      groups. PRG was associated with both RRG (p=0.002) and CaRG (p=0000), but not
      with C/BRG. Correlations with surgical outcome were also explored, with lesions
      of high PRG being more likely to undergo re-excision for inadequate first wide
      local excision [odds ratio (OR)=2.1], mastectomy (OR=2.6) and nodal staging
      procedures (OR=3.8) in the whole series. Conversely, no significant correlation
      was found between PRG, RRG, CaRG and C/BRG with surgical outcome in the limited
      series. We suggest that pathological features of DCIS are associated with
      surgical outcome and may be predicted by mammography.

PMID- 17507227
TI  - Alternative foot placements for individuals with spinal cord injuries standing
      with the assistance of functional neuromuscular stimulation.
AB  - This study investigated the effects of altering foot placement for two
      individuals with spinal cord injuries (SCI) that stood using functional
      neuromuscular stimulation (FNS) as compared to an able-bodied subject group. FNS
      assisted standers used parallel bars as needed for support, while the able-bodied
      group stood hands-free. Three different foot placements were tested: side-by
      side, wide, and modified tandem. For SCI subjects, the percentage of body weight
      loaded on the feet was not greatly affected by foot placement, which potentially
      could be altered to provide postural benefits during functional tasks.
      Anterior/posterior (A/P) center of pressure (COP) origins tended to be located
      more anterior in the base of support for SCI subjects as compared to able-bodied
      subjects. SCI subjects also tended to have medial/lateral (M/L) COP excursions
      that were larger than able-bodied subjects. The sacrum appeared to hold some
      promise as a sensor location for monitoring A/P postural sway, but movements in
      the M/L direction were inconsistent and will require additional study. General
      guidelines such as positioning the A/P COP more posterior in the base of support
      and feedback concerning excessive M/L COP displacements may be useful to improve
      standing performance for SCI subjects. In addition, the modified tandem placement
      was an effective alternative for making postural adjustments in one SCI subject
      who experienced excessive right knee flexion with other foot placements.

PMID- 17507228
TI  - Conformation selectivity in the binding of diazepam and analogues to alpha1-acid
      glycoprotein.
AB  - Diazepam, a 1,4-benzodiazepine lacking chiral centre, exists in an equimolar
      mixture of two chiral conformers. Induced circular dichroism spectra for the
      binding of diazepam and its 3,3-dimethyl substituted analogues to alpha1-acid
      glycoprotein (AGP) revealed that opposite to human serum albumin, AGP preferably
      binds the P-conformers. Accordingly, slightly favoured binding of (R)-enantiomers
      of 3-alkyl derivatives having P-conformation was found. In case of 3-acyloxy
      derivatives, however, AGP preferably binds the (S)-enantiomers. Studies with the
      separated genetic variants of AGP proved similar binding affinities, but markedly
      different conformation selectivities. For diazepam bound by the F1-S variant, a
      P/M selectivity of about 2 could be estimated.

PMID- 17507230
TI  - Chemical and biological effects of substitution of the 2-position of ring
      expanded ('fat') nucleosides containing the imidazo[4,5-e][1,3]diazepine-4,8
      dione ring system: the role of electronic and steric factors on glycosidic bond
      stability and anti-HCV activity.
AB  - The attempted removal of the aralkyl group of 2-bromo-1-p-methoxybenzyl-6
      octylimidazo[4,5-e][1,3]diazepine (ZP-33) with trifluoroacetic acid resulted in
      replacement of the bromo group with a carbonyl at position-2 in addition to the
      desired deprotection at the 1-position. 2'-Deoxynucleosides of 2-bromo
      substituted-imidazole-4,5-diesters (ZP-35 and ZP-103) were synthesized by direct
      glycosylation of the corresponding heterocycles. The attempted ring-closure of
      the above nucleosides resulted in deglycosylation to form the starting
      heterocycles. The 2-phenyl derivatives of the above nucleosides (ZP-45 and ZP-73)
      were successfully prepared by Suzuki coupling with the appropriate phenylboronic
      acids, but the attempted ring-closure with guanidines to form the desired 5,7
      fused ring-expanded nucleosides (RENs) resulted once again in the formation of
      the corresponding heterocyclic aglycons (ZP-64 and ZP-75). The first successful 2
      substituted REN (ZP-110) was synthesized by replacing the 2-deoxyribose sugar
      moiety with a ribosyl group and replacing the bromo group with a p-methoxyphenyl
      substituent at the 2-position. A number of imidazole riboside diester precursors
      containing a substituted phenyl group at the 2-position were synthesized in order
      to prepare analogues of ZP-110. The substituents on the phenyl ring included a
      variety of electron-donating or electron-withdrawing groups operating through
      inductive and/or resonance effects. However, the final ring-closure of the
      diesters with guanidines in order to prepare RENs was successful only in a
      limited number of cases, including the ones containing a p-fluorophenyl (ZP-121),
      a m-methoxyphenyl (ZP-122), or an unsubstituted phenyl (NZ-53) at the 2-position.
      Deglycosylation and incomplete ring-closure of the intermediates were the major
      problems encountered with most other cases. The stability of glycosidic bonds was
      found to be dependent on several factors including, but not limited to, the
      electron-donating inductive effect of the 2-phenyl substituents and the
      temperature of the reaction medium. The three target RENs ZP-110, ZP-121, and ZP
      122 were screened for in vitro anti-HCV activity, employing an HCV RNA replicon
      assay. While ZP-121 was inactive, the other two compounds showed only weak anti
      HCV activity.

PMID- 17507231
TI  - Tandem ligation at X-Cys and Gly-Gly positions via an orthogonally protected
      auxiliary group.
AB  - 4,5-dimethoxy-2-mercaptobenzylamine (Dmmb) has been protected by acetamidomethyl
      (Acm) and incorporated into a peptide thioester for use in tandem native chemical
      ligation. Upon ligation between the thioester and a Cys-peptide, Acm was removed
      from Dmmb using silver acetate, and a second ligation reaction was done at the
      Dmmb position. Dmmb removal using TFMSA-TFA effected overall tandem ligation at X
      Cys and Gly-Gly.

PMID- 17507232
TI  - Antiangiogenic versus cytotoxic activity in analogues of aeroplysinin-1.
AB  - A series of analogues of the potentially angiogenic inhibitor aeroplysinin-1 1
      were synthesized and their in vitro antiangiogenic and cytotoxic activities
      evaluated. In the case of epoxy ketone 6 and azlactone 36 the relationship
      sprouting inhibition assay/cytotoxicity in BAE cells was enhanced by one order
      and two orders of magnitude, respectively, with respect to the reference. These
      results imply more specific antiangiogenic properties for the synthesized
      derivatives.

PMID- 17507233
TI  - Synthesis of sialic acid derivatives as ligands for the myelin-associated
      glycoprotein (MAG).
AB  - The trisaccharide substructure 13 of the ganglioside GQ1balpha shows a remarkable
      affinity for the myelin-associated glycoprotein (MAG). In the search for
      structurally simplified and pharmacokinetically improved mimics of 13, sialosides
      with modifications at the reducing and non-reducing end were synthesized. The
      biological evaluation of mimics 12a-o was performed in a competitive target-based
      assay. It was found that the relative inhibitory potency (rIP) of antagonist 12h
      was enhanced by more than 1000-fold in comparison to the reference trisaccharide
      13, despite the former having a much simpler structure. In addition, the sialic
      acid derivatives, for example, 12h, have clearly improved pharmacokinetic
      properties due to the presence of aromatic moieties, a lower molecular weight,
      and a reduced number of polar hydroxy functions compared to the reference
      compound 13.

PMID- 17507234
TI  - MsCYS1, a developmentally-regulated cystatin from alfalfa.
AB  - Several roles have been attributed to cystatins in plants, ranging from the
      regulation of host [endogenous] cysteine proteases to the inhibition of
      herbivorous pest [exogenous] proteases. We report here the cloning, expression
      and functional characterization of a novel cystatin from alfalfa, Medicago sativa
      L. The new sequence, isolated from a cDNA expression library prepared from young
      leaves, encodes a protein, MsCYS1, with the typical inhibitory motifs of
      cystatins, namely the central signature motif QxVxG, a GG doublet in the N
      terminal trunk, and a W residue in the C-terminal region, about 30 amino acids
      distant from the central inhibitory motif. As shown by a protein-based
      phylogenetic reconstruction, MsCYS1 is a close relative of other cystatins from
      Fabaceae presumably involved in the regulation of endogenous proteases. This
      cystatin is developmentally regulated in stems and leaves, and not induced by
      stress signals including methyl jasmonate, known to activate cystatins involved
      in plant defense. A recombinant form of MsCYS1 expressed in Escherichia coli was
      shown to strongly inhibit alfalfa leaf cysteine proteases while showing weak
      affinity for the digestive cysteine proteases of different herbivorous pests.
      Overall, these observations suggest an endogenous protease regulatory role for
      MsCYS1, possibly associated with the early development of stems and leaves.

PMID- 17507235
TI  - Removal of trace metals by Sorghum bicolor and Helianthus annuus in a site
      polluted by industrial wastes: a field experience.
AB  - Using the perspective of full scale application of phytoremediation techniques,
      research is focusing on the optimization of agronomic practices. Two annual high
      biomass yield crops, Sorghum bicolor and Helianthus annuus, were grown in a
      polymetallic soil. The experimental site, polluted by pyrite cinders, is located
      in an industrial site that has been listed in the clean-up national priority list
      since 2001. Specific aims of this work were to observe the concentration of
      metals in plants during the crop cycle and to establish the amount of metal
      removed by the crops. The field trial, arranged in a randomized block design,
      started in 2005. The concentrations of heavy metals in the soil were: As 309, Cd
      4.29, Co 50.9, Cu 1527 and Zn 980mg kg(-1). The crops grown on the polluted soil
      received mineral fertilization (Fert) and organic amendment (Org), while plants
      in control soil (Ctrl) did not receive anything. The plots were watered during
      the crop cycle during two drought periods, using a sprinkler irrigation system.
      The phytoextraction potential of crops was estimated during the whole growth
      cycle and the plant biomass that was collected in each sampling date was ICP
      analyzed. Plant-biomass growth curves were obtained. The concentrations of the
      metals in the shoots and in the total plant biomass were recorded. Finally, the
      metal removal was calculated for the harvestable parts of the crops. The
      amelioration of the nutritive status of the substrate that resulted, was highly
      effective for the biomass yield. However, fertilization and soil amendment did
      not heighten the concentration of metals in the harvestable tissue of the plants
      during the crop cycle. In some cases, organic matter appeared to bind the
      elements making them less available for the plants. The evaluation of the
      potential of phytoremediation of our plants compared to other crops in terms of
      metal removal was positive. Our results of metal removal are consistent with the
      results from other in situ experiments. The Zn removal by S. bicolor and H.
      annuus reached about 2000g ha(-1) and 1000g ha(-1), respectively.

PMID- 17507236
TI  - Plasma levels and vascular effects of vasopressin in patients undergoing coronary
      artery bypass grafting.
AB  - OBJECTIVE: Recent studies have suggested that endogenous vasopressin (AVP) acts
      as a spasmogen during coronary artery bypass grafting (CABG). Given that AVP
      could induce vasospasm in the grafted vessel, we assessed the release of this
      peptide during and after CABG, and explored ways of counteracting its contractile
      effect on the internal mammary artery (IMA). METHODS: Plasma levels of AVP were
      determined by radioimmunoassay in 16 patients before, during and after CABG.
      Using isometric force recording techniques, we also investigated the mechanisms
      involved in the contractile effect of AVP in ring preparations of IMA specimens
      taken from 95 patients. RESULTS: Plasma AVP levels peaked after the start of
      cardiopulmonary bypass (CPB) and correlated well with serum osmolality (Pearson's
      r=0.9490; P<0.0001; n=16). An inverse correlation was observed between plasma AVP
      levels recorded at this stage and the maximal contraction induced in vitro by AVP
      in vascular rings from the same patients (Pearson's r=-0.6968; P<0.01; n=16). No
      change in the AVP response was produced by endothelium removal, exposure to the
      NO precursor (3 x 10(-4)M L-arginine), inhibition of nitric oxide (NO) synthase
      (3 x 10(-5) M L-NAME) or soluble guanylate cyclase (3 x 10(-6) M 1H
      [1,2,4]oxadiazol [4,3,-alpha]quinoxalin-1-one (ODQ)), removal of the superoxide
      anion (100 U/ml superoxide dismutase (SOD) plus 1200 U/ml catalase) or hydroxyl
      radical (10(-4) M deferoxamine), or specific alpha1 - (10(-6) M prazosin) or
      endothelin (10(-5) M bosentan) receptor antagonism. In contrast, adenylate
      cyclase activation (3 x 10(-8) M forskolin) reduced the contractile response to
      AVP, while prostanoid synthesis (3 x 10(-6) M indomethacin) inhibition and
      blockade of Ca2+ -activated potassium channels (KCa) (10(-3) M tetraethylammonium
      (TEA)) enhanced AVP contraction. Age, gender and smoking also modified the AVP
      response. CONCLUSION: Our findings suggest a role for AVP as a modulator of
      vascular tone in human IMA. The effect of AVP is dependent on prostanoids and
      Ca2+ -activated K+ channels, so its dysfunction in pathophysiological
      cardiovascular processes could mean that AVP, among other factors, produces
      vasospasm in IMA grafts.

PMID- 17507237
TI  - Histamine releasibility and expression of Lyn and Syk kinases in Indian subjects
      and role of less potent IL-3 in non-releaser basophils.
AB  - BACKGROUND: Allergen-mediated activation of the IgE signal pathway in basophils
      and mast cells leads to release of mediators in-vitro and in-vivo systems.
      However, basophils from 10% to 20% of the population do not release histamine and
      other mediators on activation of the IgE signal transduction pathway and this has
      been attributed to the absence of tyrosine kinases Lyn and Syk. Interestingly,
      when these non-releaser basophils are incubated with the IL-3, it leads to the
      recovery of the histamine releasibility. OBJECTIVE: To investigate histamine
      releasibility in the Indian population and to evaluate the role of IL-3 with
      reference to non-releaser phenotypes. METHODS: Peripheral blood basophils from
      healthy adults were purified by density gradient centrifugation and negative
      immuno-selection. Histamine release assay was performed fluorometrically.
      Assessment of Lyn and Syk expression were carried out by flow-cytometry. SNP
      analysis in the IL-3 gene was carried by sequencing analysis. RESULTS: Histamine
      release after ConA challenge varied greatly from 0% to 100% in Indian subjects.
      Eighteen percent subjects showed less than 5% histamine release (non-releasers).
      Flow-cytometric analysis revealed a significantly reduced expression of Lyn and
      Syk kinases in basophils (p<0.05). Histamine release also significantly
      correlated with expression of Lyn and Syk kinase (p<0.05). Non-releasers showed
      the presence of SNP at +79 (T-C), which leads to the one amino acid change at 8th
      position in the mature IL-3 from serine to proline. CONCLUSIONS: About 18% of the
      Indian subjects studied showed non-releaser phenotype and also had reduced Lyn
      and Syk kinase expression. Non-releasers have also shown the presence of less
      potent isoform of IL-3/P8, which is suspected to be responsible for the non
      releaser phenotype. This needs to be extended to a larger sample size and could
      be a potential target for the development of therapeutics for allergic patients.

PMID- 17507238
TI  - Immunoaffinity purification and characterization of RNA polymerase from
      Shewanella oneidensis.
AB  - Shewanella oneidensis is of particular interest for research because of its
      unique ability to use a variety of metals as final respiratory electron acceptors
      and reduce them into insoluble oxides. A collection of monoclonal antibodies
      (mAbs) that were prepared towards Escherichia coli RNA polymerase (RNAP) was
      tested for reactivity with proteins extracted from S. oneidensis. Two polyol
      responsive monoclonal antibodies (PR-mAbs) were used to purify RNA polymerase
      from S. oneidensis using immunoaffinity purification techniques. A collection of
      mAbs towards E. coli sigma subunits was also examined for cross-reactivity with
      S. oneidensis proteins. Reactions were identified with mAbs to E. coli sigma(70)
      and sigma(54). These mAbs will be useful tools for immunoaffinity purifying and
      studying the transcriptional machinery of S. oneidensis.

PMID- 17507239
TI  - Optimized expression from a synthetic gene of an untagged RNase H domain of human
      hepatitis B virus polymerase which is enzymatically active.
AB  - The RNase H domain of human hepatitis B virus (HBV) polymerase is an attractive
      molecular target for the development of new anti-HBV drugs. In this study, a
      synthetic gene coding for HBV RNase H was assembled from 12 oligonucleotides and
      expressed in Escherichia coli. The encoded protein was then recovered from
      inclusion bodies, purified, and refolded by a dilution-dialysis procedure in the
      presence of a low concentration of lauroylsarcosine (0.01%). The presence of the
      detergent was an absolute requirement for solubility, suggesting that the
      untagged RNase H might have exposed hydrophobic regions that need to be shielded
      from the solvent. The structural identity of the protein was confirmed by N
      terminal amino acid sequence analysis and mass spectrometry. The enzymatic
      activity of HBV RNase H was then tested by a recently developed fluorometric
      assay and was found to be only slightly lower than that registered with the
      entire HIV-1 reverse transcriptase. Finally, a structural model of the enzyme
      showed that H715, R744 and K745 may be involved in substrate recognition.

PMID- 17507240
TI  - EMG normalization to study muscle activation in cycling.
AB  - The value of electromyography (EMG) is sensitive to many physiological and non
      physiological factors. The purpose of the present study was to determine if the
      torque-velocity test (T-V) can be used to normalize EMG signals into a framework
      of biological significance. Peak EMG amplitude of gluteus maximus (GMAX), vastus
      lateralis (VL), rectus femoris (RF), biceps femoris long head (BF), gastrocnemius
      medialis (GAS) and soleus (SOL) was calculated for nine subjects during isometric
      maximal voluntary contractions (IMVC) and torque-velocity bicycling tests (T-V).
      Then, the reference EMG signals obtained from IMVC and T-V bicycling tests were
      used to normalize the amplitude of the EMG signals collected for 15 different
      submaximal pedaling conditions. The results of this study showed that the
      repeatability of the measurements between IMVC (from 10% to 23%) and T-V (from 8%
      to 20%) was comparable. The amplitude of the peak EMG of VL was 99+/-43% higher
      (p<0.001) when measured during T-V. Moreover, the inter-individual variability of
      the EMG patterns calculated for submaximal cycling exercises differed
      significantly when using T-V bicycling normalization method (GMAX: 0.33+/-0.16
      vs. 1.09+/-0.04, VL: 0.07+/-0.02 vs. 0.64+/-0.14, SOL: 0.07+/-0.03 vs. 1.00+/
      0.07, RF: 1.21+/-0.20 vs. 0.92+/-0.13, BF: 1.47+/-0.47 vs. 0.84+/-0.11). It was
      concluded that T-V bicycling test offers the advantage to be less time and energy
      consuming and to be as repeatable as IMVC tests to measure peak EMG amplitude.
      Furthermore, this normalization method avoids the impact of non-physiological
      factors on the amplitude of the EMG signals so that it allows quantifying better
      the activation level of lower limb muscles and the variability of the EMG
      patterns during submaximal bicycling exercises.

PMID- 17507241
TI  - Biologic resurfacing of the arthritic glenohumeral joint: Historical review and
      current applications.
AB  - In recent years there has been a resurgence of interest in the use of biologic
      resurfacing of the glenoid for the treatment of glenohumeral arthritis in younger
      patients. We review the history as well as the current applications of this
      procedure.

PMID- 17507242
TI  - Intra-articular pain pump catheter breakage after arthroscopic shoulder surgery:
      a case series.

PMID- 17507243
TI  - Ease of tying arthroscopic knots.
AB  - To date, there is no comprehensive study that determines which arthroscopic knots
      are easiest to learn to tie. In this study, 23 surgeons in training graded 10
      arthroscopic knots with regard to ease of learning and tying using a 10-cm visual
      analog scale for No. 2 Ethibond and No. 1 polydioxanone (PDS) II suture.
      Statistical analysis was performed with analysis of variance and the Tukey
      Studentized range (HSD) test for post hoc analysis with a significant value of P
      < .05. The Tennessee slider, Duncan loop, Revo knot, and Nicky's knot were the
      easiest knots to tie by use of both Ethibond and PDS suture. The Field knot and
      double-twist knot were consistently the hardest knots to tie. Knots tied with
      Ethibond were easier to tie than knots tied with PDS. Novice surgeons should
      consider using the Revo knot when developing their arthroscopic knot-tying
      skills. Once they have mastered this knot, they can consider adding more
      difficult knots to their repertoire.

PMID- 17507244
TI  - Lateral meniscus allograft biologic glenoid arthroplasty in total shoulder
      arthroplasty for young shoulders with degenerative joint disease.
AB  - To avoid potential polyethylene problems in younger shoulders with degenerative
      joint disease (DJD) requiring arthroplasty, lateral meniscus allograft (LMA) was
      used as a biologic resurfacing of the glenoid. We report preliminary, short-term
      results of this technique in a younger, higher-demand population. The shoulders
      of 20 men and 10 women, with an average age of 42 years (range, 18 to 52 years),
      underwent total shoulder arthroplasty with a LMA. A metallic prosthesis was used
      on the humerus. Etiology of the DJD was osteoarthritis in 16, postinstability
      surgery in 8, traumatic in 4, and failed open reduction with internal fixation in
      2. Twenty-two (73%) had previous shoulder surgery. Preoperative average scores
      were American Shoulder and Elbow Surgeons (ASES), 38; Simple Shoulder Test (SST),
      3.3; and Visual Analogue Scale (VAS), 6.4. The average active forward elevation
      was 96 degrees and external rotation was 26 degrees . Average follow-up was 18
      months (range, 12 to 48 months). Postoperative average scores were ASES, 69; SST,
      7.8; and VAS, 2.3. Active forward elevation was 139 degrees and external rotation
      was 53 degrees . All were significant improvements (P < .02). Most (94%) would
      have the surgery again. Radiologic evaluation at 1 year revealed an average joint
      space of 1.8 mm on anteroposterior views and 1.6 mm on axillary views. Five
      complications (17%) occurred within the first postoperative year, all of which
      required reoperation. Pain resulted in 2 conversions to a polyethylene glenoid.
      Polyethylene glenoids in young shoulders risk early failure. For young, high
      demand shoulders with DJD requiring arthroplasty, the LMA shows promise. Most
      problems presented within the first year. Although not perfect, it provided
      significant pain relief, range-of-motion gains, and patient satisfaction without
      the risk of poly wear or loosening. Longer-term follow-up will be required to
      determine ultimate durability.

PMID- 17507245
TI  - The effect of growth differentiation factor-5-coated sutures on tendon repair in
      a rat model.
AB  - Tendon ruptures are common injuries that are often treated surgically. Growth
      Differentiation Factor-5 (GDF-5) has been shown to accelerate tendon healing with
      varying degrees of success. We used a novel technique to apply recombinant human
      GDF-5 (rhGDF-5) to suture and hypothesized that controlled, local delivery of
      rhGDF-5 can be used to enhance tendon repair. Tendons of 92 rats were transected
      and repaired with sutures. All researchers were blinded to the following
      treatment groups (24 rats in each group): 0 rhGDF (control), 24 ng/cm rhGDF, 55
      ng/cm rhGDF, and 556 ng/cm rhGDF. Rats were euthanized at 3 weeks (n = 48) and at
      6 weeks (n = 48). Sutures were coated with rhGDF-5 using a novel dip-coat
      technique. Enzyme-linked immunosorbent assay confirmed consistent and
      reproducible delivery of rhGDF-5. Within each group, 8 were tested
      biomechanically, and 4 were assessed histologically. Histologic grading at 3
      weeks showed improved healing in tendons repaired with coated suture versus
      controls. By 6 weeks, there were no significant differences. At 3 weeks, minimal
      isolated cartilage formation was observed; 6-week samples showed more extensive
      presence, typically surrounding suture fibers. At 3 weeks, tendons repaired with
      rhGDF-5-coated sutures resulted in significantly higher ultimate tensile load and
      stiffness compared with control sutures (P < .05) At 6 weeks, there were no
      significant differences in the mechanical properties of repaired tendons. At 3
      weeks, rhGDF-5 induced significant tendon hypertrophy that was more pronounced
      than at 6 weeks. In addition, tendons repaired with rhGDF-5 showed an increased
      rate of healing versus control repairs at 3 weeks. This study showed that a novel
      dip-coating technique can be used to deliver growth factors in varying
      concentrations to local repair sites to accelerate tendon healing.

PMID- 17507246
TI  - Bone grafting for glenoid bone deficiencies in shoulder arthritis: a review.
AB  - Bone loss in the glenoid in the face of shoulder arthritis can be managed in
      selected cases with bone grafting. This article reviews the literature and uses
      this clinical experience to make recommendations for the surgical management of
      glenoid bone loss in cases of osteopenia, dysplasia, bone loss created by the
      arthritis, and loss that occurs in the glenoid related to failed shoulder
      arthroplasty.

PMID- 17507247
TI  - Indwelling interscalene catheter use in an outpatient setting for shoulder
      surgery: technique, efficacy, and complications.
AB  - Indwelling interscalene catheters are utilized for inpatient postoperative pain
      control after shoulder surgery. Improved medical equipment and advanced
      techniques may allow safe and efficacious outpatient use. One hundred and forty
      four consecutive indwelling interscalene catheter placements were reviewed to
      determine adverse events, complications, and efficacy. Real-time ultrasound
      guided catheter placement technique is described. Post-anesthesia care unit
      (PACU) narcotic consumption and last recorded pain score were reviewed to gauge
      efficacy. The catheter placement technique was 98% successful. There were 14
      (9.7%) minor adverse events including inadequate analgesia (8), accidental
      catheter removal (4) of disconnection (1), and shortness of breath (1). The
      single complication (0.7%) was a small apical pneumothorax. The average PACU
      narcotic consumption in intravenous morphine equivalents was 1.7 mg. The average
      last recorded PACU pain score on a scale of 1 to 10 was 0.6. Catheter placement
      under real-time ultrasound guidance is accurate. Outpatient use of indwelling
      interscalene catheters is safe and efficacious.

PMID- 17507248
TI  - Experiences with sheep as an animal model for shoulder surgery: strengths and
      shortcomings.
AB  - Sheep (and goats) are a convenient large-animal model for rotator cuff repair
      because of availability, ease of handling and housing, animal cost, and
      acceptance to society as a research animal. Tenotomy of the infraspinatus tendon
      and subsequent reattachment to the proximal humerus is useful to address the
      biomechanical, histologic, and biochemical processes of rotator cuff repair.
      Detaching this tendon and immediately reattaching it does not represent the
      clinical picture but serves as a relatively rapid way to screen different suture
      anchors, suture patterns, scaffolds, growth factors, and other biologics or a
      combination of these treatments to enhance the healing process. To minimize
      spontaneous reattachment and reproduce a chronic rotator cuff injury, the end of
      the tendon can be covered and then reattached 4 weeks later if bone-to-tendon
      healing is to be evaluated. This chronic model is useful to understand the
      biology (degree of muscle atrophy and fatty infiltration) of rotator cuff muscles
      as well as innovative methods of repair. Close-stall confinement is required
      during the convalescence in acute and chronic studies. Ultrasound in the awake
      animal can be used to monitor gap formation and tissue organization. Sheep have
      also been used to determine whether capsular healing after plication is
      equivalent to open capsular shift.

PMID- 17507249
TI  - Hyperbaric oxygen therapy facilitates surgery on complex open elbow injuries:
      preliminary results.
AB  - Complex open elbow injuries present a significant challenge to orthopaedic
      surgeons because of the poor potential for achieving a good functional level,
      even given good anatomic realignment. Associated massive soft-tissue damage
      impedes surgical fixation, delays rehabilitation, and therefore, further
      deteriorates the functional outcome. We studied a prospective, consecutive series
      of 16 patients with complex open elbow injuries who were treated with a
      combination of treatment modalities including early bony stabilization,
      debridement of soft tissue, and early coverage. The treatment protocol also used
      hyperbaric oxygen therapy to facilitate immediate internal fixation. The median
      value of the Mangled Extremity Severity Score was 5.5 (range, 3-10). Successful
      reconstruction was achieved in all 16 patients. No deep infection occurred, but
      there were 3 self-limited superficial infections. The average elbow functional
      result at 12 months after surgery, based on the Mayo score system, was good (mean
      value, 80.9; range, 55-100). Of the patients, 75% achieved satisfactory
      functional results for the elbow. The results of this study demonstrate that the
      studied treatment protocol provides a promising alternative for managing these
      complex open elbow injuries.

PMID- 17507250
TI  - Effect of total shoulder replacements on airport security screening in the post
      9/11 era.
AB  - There are few reports in the literature on the effect of orthopaedic implants on
      airport security devices and none on shoulder arthroplasty implants after
      September 11, 2001. Since 9/11, airport security screening devices have become
      more sensitive in response to the increasing threat of terrorism. Often, patients
      with joint implants activate the metal detectors and are subsequently subjected
      to more intensive screening. We assess the effects of shoulder joint implants on
      different airport security devices and what effect the results had on passenger
      travel. In this study, 154 patients who had previously undergone shoulder
      replacement responded to a questionnaire regarding their travel experiences after
      9/11. Of these, 85 had flown during the time period studied (47 men and 38 women;
      mean age, 67.8 years); 79 had traveled domestically (mean, 7 flights), and 22 had
      taken international flights (mean, 6.1 flights). The questionnaire addressed each
      patient's height/weight, the number of flight segments flown (domestic and
      international), the number of times that a patient activated the doorway
      alarm/wand alarm, and the effect of a card stating that the patient had joint
      replacement (when applicable). On average, patients with shoulder replacement
      traveling domestically activated the security gate 52% of the time. The average
      for international travel was 42%. Of the patients who flew both domestically and
      internationally, there was a high correlation of activation (R = 0.54). Twenty
      six patients had multiple joint implants (mean, 2.8). Multiple joint implants
      caused increased alarm activation (P < .001). All patients reported that their
      travel was delayed during the instances of security activation. There was no
      statistically significant effect of body mass index, height, weight, age, or sex
      on security device activation. Of the patients, 71% were told by their doctor
      that the shoulder replacement may activate security devices. Of these, 46 were
      given a card by their doctor indicating the presence of a total joint implant. In
      only 30% of the security encounters of these patients did the card expedite the
      screening process. This is the largest study on the effects of joint implants,
      and shoulder implants in particular, on airport security devices and the only one
      that has analyzed the data of post-9/11 travel. Patients traveling after total
      shoulder replacement are often delayed and subjected to more rigorous screening
      when traveling, especially in the post-9/11 environment. Doctors often warn their
      patients of potential problems and may try to avert this by giving them cards
      documenting the presence of a joint implant. The acceptance of these cards is
      sporadic. This study raises the importance of notifying patients of potential
      security delays, especially those with multiple joint implants, as they may
      directly affect travel plans. In addition, these patients may benefit from the
      establishment of an international joint registry.

PMID- 17507251
TI  - The influence of implant articular thickness and glenohumeral conformity on
      stability of an all-metal glenoid component.
AB  - The objective of this study was to determine the effect of implant thickness and
      glenohumeral conformity on fixation of an all-metal glenoid component. A
      stainless steel glenoid component was designed and implanted in 10 cadaveric
      scapulae. A testing apparatus capable of producing a loading vector at various
      angles, magnitudes, and directions was used. The independent variables included 6
      directions and 3 angles of joint load, 3 implant thicknesses, and 4 glenohumeral
      conformities. Implant micromotion relative to bone was measured by use of 4
      displacement transducers at the superior, inferior, anterior, and posterior
      sites. The components displayed a consistent response to loading of ipsilateral
      compression and contralateral distraction. Stability decreased as the load
      application angle increased (P < .05). A decrease in the implant thickness and
      glenohumeral conformity resulted in increased implant stability (P < .05).
      Decreasing implant thickness and glenohumeral conformity reduce the eccentric
      component of loading and may improve the durability of glenoid implants.

PMID- 17507252
TI  - Ultrasonographic examination of the synovial fold of the radiohumeral joint.
AB  - This report describes the anatomy of the synovial fold of the radiohumeral joint
      and assesses its visibility by ultrasonography. Forty-nine fresh cadaver
      radiohumeral joints were examined by ultrasonography before and after
      intraarticular saline injection and then dissected. Digital photos were taken
      before and after the joint capsule was excised. The relative coverage of the
      radial head by the fold was calculated. Synovial folds were observed in all
      specimens. Forty-three had anterior and posterior lobes. The synovial fold
      covered an average of 28% of the radiocapitellar joint surface of the radial
      head. The sensitivity of the ultrasonography was 81%, 46%, and 85% from the
      anterior, lateral, and posterior aspects of the radiohumeral joint, respectively.
      Intraarticular saline injection improved the sensitivity to 96%, 67%, and 94%,
      respectively. The synovial fold is a consistent anatomic structure, and
      ultrasonography can be a useful preoperative diagnostic tool.

PMID- 17507253
TI  - Comment to: overlap cases of eyelid myoclonia with absences and juvenile
      myoclonic epilepsy.

PMID- 17507254
TI  - Focal akinetic seizures as the only clinical manifestation of partial epilepsy.
AB  - Episodic hemipareis is usually thought to have a vascular etiology. Ictal paresis
      during seizures usually occurs with other clinical signs. The exact mechanism by
      which weakness occurs during seizures is difficult to determine as positive and
      negative motor phenomenona occur in rapid succession. This case describes a girl
      with episodic ictal hemiparesis since infancy as the only clinical seizure
      manifestation with VEEG suggesting mesial frontal ictal onset.

PMID- 17507255
TI  - Measurement of synovial fluid volume using urea.
AB  - OBJECTIVE: To examine the utility of using urea concentrations for determining
      Synovial Fluid (SF) joint volume in effused and non-effused joints. METHODS: Knee
      joint SF was aspirated from 159 human study participants with symptomatic
      osteoarthritis of at least one knee either directly (165 knees) or by lavage (110
      knees). Serum was obtained immediately prior to SF aspiration. Participants were
      asked to rate individual knee pain, aching or stiffness. SF and serum urea levels
      were determined using a specific enzymatic method run on an automated CMA600
      analyzer. Cell counts were performed on direct SF aspirates when volume
      permitted. The formula for calculating SF joint volume was as follows:
      V(j)=C(D)(V(I))/(C-C(D)) with V(j)=volume of SF in entire joint,
      C(D)=concentration of urea in diluted (lavage) SF, V(I)=volume of saline injected
      into joint, and C=concentration of urea in undiluted (neat) SF derived below
      where C=0.897(C(S)) and C(s)=concentration of urea in serum. RESULTS: There was
      an excellent correlation (r(2)=0.8588) between SF and serum urea in the direct
      aspirates with a ratio of 0.897 (SF/serum). Neither urea levels nor the SF/serum
      ratio showed any correlation with Kellgren Lawrence (KL) grade, or cell count.
      While urea levels increased with age there was no change in the ratio.
      Intraarticular SF volumes calculated for the lavaged knees ranged from 0.555 to
      71.71ml with a median volume of 3.048ml. There was no correlation of SF volume to
      KL grade but there was a positive correlation (P=0.001) between SF volume and
      self-reported individual knee pain. CONCLUSION: Our urea results for direct
      aspirates indicate an equilibrium state between serum and SF with regard to the
      water fraction. This equilibrium exists regardless of disease status (KL grade),
      inflammation (cell count), or age, making it possible to calculate intraarticular
      volume of lavaged joints based upon this urea method. Most of the joint volumes
      we calculated fell within the previously reported range for normal knees of 0.5
      4.0ml. The positive correlation between SF volume and knee symptoms reinforces
      the clinical utility of this method for quantifying SF volume.

PMID- 17507256
TI  - Maternal hen calls modulate memory formation in the day-old chick: the role of
      noradrenaline.
AB  - Facilitation of memory for discriminative learning in young chicks is enhanced
      following exposure to a synthesized rhythmic auditory stimulus. Increased
      arousal, mediated by noradrenergic activation, is believed to underlie this
      effect. In this report we examine whether ethologically relevant rhythmic
      auditory stimuli produce the same noradrenaline-mediated memory enhancement in
      neonate chicks (Gallus gallus domesticus). Maternal hen attraction calls which
      contained a rhythmic pattern were found to facilitate retention. Intracerebral
      injection of noradrenaline or the beta(2)-adrenergic antagonist propranolol
      demonstrated that this enhancement is likely to be mediated by noradrenergic
      activation of central beta(2)-noradrenergic receptors. In contrast, a rhythmic
      alarm call inhibited retention. Subcutaneous injection of the alpha(1)-adrenergic
      antagonist prazosin revealed that this impairment may be due to higher arousal
      levels resulting in activation of alpha(1)-noradrenergic receptors. It is
      concluded that the maternal hen calls of domestic chickens can influence the
      memory ability of the offspring via noradrenaline release in the brain. The
      current data suggest that call meaning and rhythmicity interact to yield the
      appropriate levels of beta(2)-adrenergic activation required to facilitate
      retention for a discriminative task.

PMID- 17507257
TI  - Estrogens and progestins enhance spatial learning of intact and ovariectomized
      rats in the object placement task.
AB  - Steroid modulation of cognitive function has focused on estrogen (E(2)), but
      progestins naturally co-vary with E(2) and may also influence cognitive
      performance. Spatial performance in the object placement task over endogenous
      hormonal states in which E(2) and progestins vary, and when E(2) and/or
      progestins were administered, was examined. Experiment 1: Rats in proestrus or
      estrus had significantly better performance in the object placement task than did
      diestrus rats. Experiment 2: Rats in the third trimester, post-partum, or
      lactation exhibited significantly better performance in the object placement task
      than did rats in the first trimester. Experiment 3: Ovariectomized (ovx) rats
      administered 17beta-estradiol (0.9 mg/kg), subcutaneously (sc), progesterone (P;
      4 mg/kg, sc), or E(2) and P, immediately after training in the object placement
      task, performed significantly better when tested 4h later, than did control rats
      administered vehicle (sesame oil 0.2 cc). Experiment 4: ovx rats administered
      E(2) or P with a 1.5h delay after training in the object placement task, did not
      perform differently than vehicle-administered controls. Experiment 5: ovx rats
      administered post-training E(2), which has a high affinity for both E(2) receptor
      (ER)alpha and beta isoforms, or propyl pyrazole triol (PPT; 0.9 mg/kg, sc), which
      is more selective for ERalpha than ERbeta, had significantly better performance
      in the object placement task than did rats administered vehicle or
      diarylpropionitrile (DPN; 0.9 mg/kg, sc), an ERbeta selective ligand. Experiment
      6: ovx rats administered P, or its metabolite, 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP; 4 mg/kg, sc), immediately post-training performed
      significantly better in the object placement task than did vehicle control rats.
      Thus, performance in the object placement task is better when E(2) and/or P are
      naturally elevated or when E(2), the ERalpha selective ER modulator PPT, P, or
      its metabolite, 3alpha,5alpha-THP, are administered post-training.

PMID- 17507258
TI  - The use of foam sclerotherapy for varicose veins: a survey of the members of the
      Vascular Society of Great Britain and Ireland.
AB  - OBJECTIVES: The aim was to explore the current experience and practice of
      vascular surgeons in the United Kingdom and Ireland regarding foam sclerotherapy
      for varicose veins. METHOD: A postal questionnaire was sent to 609 members of the
      Vascular Society of Great Britain and Ireland. RESULTS: There were 281 responses
      (47%). Seventy surgeons (25%) used foam sclerotherapy. Most use it selectively;
      few (29%) offer it to all patients. It was more likely to be used for recurrent
      varices (71%), in older patients (61%) and for smaller non-saphenous varices
      (67%). The majority of surgeons (69%) used sodium tetradecyl sulphate and up to a
      maximum of 10-12 ml of foam. The majority used ultrasound guidance (95%), leg
      elevation (69%) and direct pressure over the saphenofemoral or saphenopopliteal
      junction during injection (63%). Eighty per cent used compression bandaging after
      treatment, usually for 7 days (44%). Ninety percent advised compression
      stockings, usually Class II (64%) for 14 days (39%). Serious complications were
      few, but eleven surgeons had seen a deep vein thrombosis, two had seen a patient
      with a stroke and one a transient ischaemic attack. CONCLUSION: Foam
      sclerotherapy was used by a quarter of surgeons who replied to the survey.
      Aspects of technique varied considerably and studies to determine optimal
      techniques are needed. Serious complications with the technique were rare.

PMID- 17507259
TI  - Reply to letter to the editor re: Investigation on radiofrequency and laser (980
      nm) effects after endoluminal treatment of saphenous vein insufficiency in an ex
      vivo model.

PMID- 17507261
TI  - Cyanoacrylate glue versus suture in peripheral nerve reanastomosis.
AB  - OBJECTIVE: To assess the effectiveness of n-butyl-2-cyanoacrylate glue compared
      with microsuturing technique in peripheral nerve reanastomosis in rats. STUDY
      DESIGN: Fourteen young adult white rats were used. Bilateral sciatic neurotomies
      were performed in 12 of them and then reanastomosed with 3 epineural microsutures
      in the right side (study group G1) and with n-butyl-2-cyanoacrylate glue in the
      left side (study group G2). On the remaining 2 rats (control group G3), sham
      surgery was done on both sides. Biopsies were harvested 12 weeks after surgery
      and examined under light microscope using Osmic acid stains. The number of nerve
      fibers was counted in the distal and proximal nerve segments, and the results
      were analyzed and compared in all groups. RESULTS: Adequate regeneration with no
      anastomotic ruptures was seen 12 weeks after surgery in G1 and G2. The
      histomorphometric assessment showed no statistically significant difference (P =
      .960) in the neurotization index of G1 (89.01%) compared with G2 (88.97%). There
      was a significant (P = .001) reduction in the mean number of axon counts distal
      to the repair in G1 (271.3) and G2 (272.8) compared with that of the proximal
      segments of each study group (304.6 and 303, respectively, as well as to that of
      G3 (348.5). CONCLUSION: Both n-butyl-2-cyanoacrylate adhesive and 3-microsuture
      techniques showed comparable neurotization indices and were equally adequate to
      stabilize the nerve during regeneration period.

PMID- 17507260
TI  - Sarcomas and sarcomatoid tumor after radiotherapy of oral squamous cell
      carcinoma: analysis of 4 cases.
AB  - Radiation-induced sarcoma (RIS) or postirradiation sarcoma has been reported
      rarely as a long-term complication of radiation therapy (RT). We report 4 cases
      of oral sarcomas or sarcomatoid tumors with a rather short latency period after
      radiotherapy of the prior OSCC. Histopathological evaluation and
      immunohistochemical study were performed using a panel of markers including
      vimentin, cytokeratin, S-100, desmin, myoglobin, HHF-35, p53, and p16. All
      reported cases were positive for vimentin and negative for cytokeratin. Two cases
      were positive for myoglobin, desmin, or HHF-35, and were probably myogenic
      origin. One case was possibly a fibrosarcoma and the subclassification of the
      other one was not specified. Diverse expression of p53 and p16 was further
      observed in these 4 cases. Report of the complicated clinical processes and the
      analysis of genetic markers of these cases provide useful clinical and
      pathogenetic insights of mesenchymal malignancies associated with a status post
      OSCC radiation.

PMID- 17507262
TI  - Myosin heavy chain mRNA isoforms in masseter muscle before and after orthognathic
      surgery.
AB  - OBJECTIVES: Orthognathic surgery leads to changed jaw position and force vector
      of mastication to which the muscles must adapt. The aim of the present study was
      to determine the relative expression of myosin heavy chain (MyHC) messenger RNA
      (mRNA) isoforms in different types of human masseter muscle fiber under
      consideration of change in the number of occlusal contacts before and 6 months
      after surgery. STUDY DESIGN: Muscle biopsies were taken from the anterior and
      posterior parts of both sides in 30 patients with prognathic and retrognathic
      mandibles. Specific mRNA MyHC analysis was made by real-time polymerase chain
      reaction to quantify the isoforms I, IIa, and IId/x. RESULTS: There was a shift
      in the relative content from type I (46% before, 37% after) to type IIa (29%
      before, 42% after). This shift correlates with number of teeth in occlusion.
      CONCLUSIONS: Correlation between isoform shift and number of teeth in occlusion
      indicates higher mastication force which stabilizes the treatment result.

PMID- 17507263
TI  - Multiple complications due to osteoradionecrosis in a patient with
      thromboangiitis obliterans.
AB  - A case is presented of a patient with thromboangiitis obliterans (TAO) who
      developed severe necrosis of the intraoral soft tissues and maxillary and
      mandibular bone after radiotherapy for a cT2N0M0 squamous cell carcinoma of the
      soft palate. Multiple surgical procedures including partial resection of the
      mandible and maxilla and reconstruction of intraoral and extraoral defects with a
      pectoralis major myocutaneous flap and anterolateral thigh flap were performed
      with partial success. Although a causal relationship between TAO and the
      described complications cannot be verified, close monitoring of patients with TAO
      who are being treated with radiotherapy is advised.

PMID- 17507264
TI  - Influence of two different flap designs on incidence of pain, swelling, trismus,
      and alveolar osteitis in the week following third molar surgery.
AB  - OBJECTIVE: To investigate the influence of flap design on postoperative trismus,
      pain, and swelling. STUDY DESIGN: Thirty-two patients with bilateral
      symmetrically impacted mandibular third molars participated in a randomized
      prospective split mouth study. Two flap designs were used: a buccal envelope flap
      and a modified triangular flap. Postoperative pain was recorded using a
      standardized visual analog scale. Postoperative swelling was evaluated using
      laser scans of models of the patient's cheek taken before and two days after
      surgery, with the scan area being calculated using MatLab software. RESULTS:
      There were no statistical differences between the flap designs in terms of
      severity of postoperative pain or trismus. A statistically significant difference
      was observed in postoperative swelling at 2 days, with the modified triangular
      flap design being associated with increased swelling. The envelope flap design
      was associated with a higher incidence of alveolar osteitis. CONCLUSION: The flap
      designs used in this study did not adversely affect patients in terms of
      postoperative pain and trismus, and although greater extraoral swelling was seen
      with the modified triangular flap design, the clinical relevance is debatable.

PMID- 17507265
TI  - Odontogenic myxoma: review of the literature and report of 30 cases from South
      Africa.
AB  - OBJECTIVE: The purpose of the study was to analyze the clinical and radiographic
      features of central odontogenic myxomas (OM) of the jaws diagnosed over 23 years
      in a black South African patient sample. STUDY DESIGN: Records of 30 cases of OMs
      with radiographs of diagnostic quality were retrieved from 52 cases of
      histopathologically verified OMs from the archives of the Oral Health Center at
      the University of Limpopo, South Africa. The age, sex, size, location, and
      radiographic features were compared with the literature. RESULTS: The study
      consisted of 21 females and 9 males. The correlation between age and size of the
      tumor was found to be statistically significant (P = .004). Septa were shown to
      be either reorientated cortical bone or sheets of dense fibrous connective
      tissue. Indistinct borders mimicked malignancy. The most common radiographic
      feature was the tennis-racket appearance. CONCLUSIONS: Variations in radiographic
      presentation make a radiological differential interpretation of OM challenging
      because the radiographic features overlap with those of other benign and
      malignant neoplasms.

PMID- 17507266
TI  - Pain and swelling after periapical surgery related to oral hygiene and smoking.
AB  - OBJECTIVES: To evaluate pain and swelling during the first week after periapical
      surgery and its relation to patient age, gender, oral hygiene, and smoking. STUDY
      DESIGN: One hundred two patients (31 men and 71 women) with a mean age of 40.2
      years underwent periapical surgery. Age, gender, and oral hygiene and cigarette
      smoking before and during the postoperative course were noted. Pain and swelling
      scores were recorded on a descriptive 4-point scale at 2, 6, and 12 hours after
      surgery, and each day thereafter for 1 week. The data were statistically
      evaluated for significant differences. RESULTS: The highest intensity of pain
      occurred during the first 48 hours, and swelling peaked on the second
      postoperative day. Patient age and gender had no significant effect on
      postoperative symptoms (P > .05). Patients with poor oral hygiene before surgery
      presented greater pain and swelling during the first postsurgical hours, and
      smokers before surgery also suffered more pain. The number of cigarettes smoked
      in the postoperative period and oral hygiene after surgery had no effect on pain
      or inflammation (P > .05). CONCLUSIONS: Periapical surgery caused little pain and
      moderate swelling during the first 2 days after the intervention; these findings
      were more distinct in patients with poor oral hygiene before surgery and in
      smokers.

PMID- 17507268
TI  - Localization of impacted maxillary canines and observation of adjacent incisor
      resorption with cone-beam computed tomography.
AB  - OBJECTIVE: The aim of this study was to investigate with cone-beam computed
      tomography (CBCT) the locations of impacted maxillary canines and resorption of
      neighboring incisors. STUDY DESIGN: Two hundred ten impacted maxillary canines
      were analyzed using CBCT images. The locations of the impacted canines were
      assessed and angular and linear measurements were taken using NewTom proprietary
      software. In addition, root resorption of neighboring incisors was investigated.
      RESULTS: Among these impactions, 45.2% were impacted buccal-labially, 40.5% were
      impacted palatally, and 14.3% in the midalveolus. The locations varied: mesial
      labial impaction (n = 67), mesial-palatal impaction (n = 74), in situ impaction
      (n = 31), distal impaction (n = 12), horizontal impaction (n = 18), and inverted
      impaction (n = 8). Quantitive measurements further depicted these variations.
      Root resorption was present in 27.2% of lateral and 23.4% of central incisors,
      and 94.3% of these resorptions occurred where the impacted canines were in close
      contact with the incisors. CONCLUSION: The location of impacted maxillary canines
      varies greatly in 3 planes, and the resorption of neighboring permanent incisors
      is common.

PMID- 17507267
TI  - Ligneous periodontitis and gingival antioxidant status: report of two cases.
AB  - Ligneous periodontitis (LP) is a rare periodontal disease in which plasminogen
      deficiency and fibrin deposition both play a part, resulting in characteristic
      gingival enlargement and periodontal breakdown. Recent data suggest that
      oxidant/antioxidant changes are significant in the pathology of oral diseases.
      This study examines the gingival histopathology in 2 cases with LP. To examine
      the antioxidant (AO) status, the activity of the major AOs glutathione (GSH),
      catalase (CAT), and glutathione S-transferase (GST) and the malondialdehyde (MDA)
      levels, a product of lipid peroxidation, were measured and compared with healthy
      control subjects. The histopathologic examination of the gingiva revealed
      subepithelial fibrin accumulation and irregular extensive downward proliferation
      of the epithelium. Biochemical analysis showed that the CAT, GST, and MDA levels
      were higher in LP patients than in the control subjects, and the GSH level was
      lower. Our preliminary findings show that in LP, the AO capacity of the gingiva
      changes or decreases and lipid peroxidation increases, which suggests that
      oxidative stress is involved in the pathology of the periodontal breakdown
      observed in this disease.

PMID- 17507269
TI  - A guide for preparing a patient-oriented research manuscript.

PMID- 17507270
TI  - Benomyl resistance of Colletotrichum acutatum is caused by enhanced expression of
      beta-tubulin 1 gene regulated by putative leucine zipper protein CaBEN1.
AB  - Colletotrichum acutatum, the fungus causing anthracnose disease of various fruits
      and crops, has inherent resistance to benomyl. The mechanism underlying its
      resistance to benomyl remains unclear. We generated a benomyl-sensitive mutant
      CAT7-150 by transformation-mediated insertional mutagenesis. Subsequently, a
      CaBEN1 gene was isolated from CAT7-150 by plasmid rescue and sequenced. CaBEN1
      encodes a protein of 818 amino acids containing a leucine zipper motif, and the
      amino acid sequence has significant similarity to hypothetical proteins found in
      Gibberella zeae and other fungi. Disruption and complementation of the CaBEN1
      gene demonstrated that CaBEN1 was necessary for resistance to benzimidazole
      fungicides, but was not essential for mycelial growth. Northern analysis suggests
      that CaBEN1 has an important role in transcriptional activation of CaTUB1 in
      response to benomyl. Benomyl resistance of CaBEN1-disrupted transformant was
      recovered by overexpression of CaTUB1. Our results clearly demonstrate that the
      benomyl resistance is due to enhanced expression of CaTUB1, which is controlled
      by CaBEN1.

PMID- 17507271
TI  - Adjuvant effect of caffeine on acetylsalicylic acid anti-nociception:
      prostaglandin E2 synthesis determination in carrageenan-induced peripheral
      inflammation in rat.
AB  - In the present study, we report a synergistic interaction between acetylsalicylic
      acid (ASA) and caffeine (CAF) on the inhibition of nociception in a model of
      peripheral inflammation in rat; on the contrary no interaction have been found on
      anti-inflammatory effects and peripheral prostaglandin E2 (PGE-2) synthesis
      inhibition. Acute inflammation was induced by the subplantar injection of
      carrageenan into the right hind paw, and the effects of the drugs were evaluated
      from 0 to 5h. Nociception was assessed using the Randall & Selitto test, and the
      inflammatory response by plethismometry. Oral administration of ASA (10-400mg/kg)
      induced dose-related anti-nociceptive and anti-inflammatory effects. On the other
      hand, oral CAF administration (5-50mg/kg) did not show a dose-related inhibitory
      effect, neither on the inhibition of nociception nor on the inflammatory
      response. To analyze a possible interaction between both drugs a dose-response
      curve to ASA plus a fixed dose of CAF (5mg/kg) was obtained 3h after the
      injection of carrageenan, when the inflammatory pain peaked. A fixed dose of CAF
      was able to improve the anti-nociceptive, but not the anti-inflammatory, effects
      of ASA. We also assessed, by enzyme immunoassay, the effects of the combination
      on peripheral PGE-2 levels: CAF did not alter the inhibitory effect of ASA on PGE
      2 synthesis. Our results corroborate the well-known clinical effects of combining
      ASA and CAF; on the other hand, we rule out that prostaglandin synthesis
      inhibition at peripheral sites would be the mechanism responsible of the adjuvant
      anti-nociceptive effect of CAF.

PMID- 17507272
TI  - Real-time imaging of the spatial distribution of rf-heating in NMR samples during
      broadband decoupling.
AB  - Continuous radio-frequency (rf) irradiation during decoupling and spin-lock
      periods in NMR pulse sequences may lead to undesired sample heating. Heat
      sensitive samples can suffer damage from the sudden temperature rise which cannot
      be adequately compensated by the temperature control system. Moreover, as the
      heating is spatially inhomogeneous, higher temperature increases can arise
      locally than are indicated by the average increase detected by the temperature
      controller. In this work we present a technique that allows measurement of a real
      time 2D-image of the temperature distribution inside an NMR sample during an
      experiment involving rf-heating. NMR imaging methods have previously been used to
      project the temperature distribution inside an NMR sample onto a single spatial
      axis or to acquire steady-state 2D- temperature distributions. The real-time 2D
      temperature profiles obtained with our procedure provide much more detailed data.
      Our results show, that not only inhomogeneous heating but also inhomogeneous
      sample cooling contribute to the build-up of temperature gradients across the
      sample. The technique can be used to visualize rf-heating in order to protect
      sensitive samples and to experimentally test new coil geometries or to guide
      probehead design.

PMID- 17507273
TI  - Structural and functional comparison of the non-structural protein 4B in
      flaviviridae.
AB  - Flaviviridae are evolutionarily related viruses, comprising the hepatitis C virus
      (HCV), with the non-structural protein 4B (NS4B) as one of the least
      characterized proteins. NS4B is located in the endoplasmic reticulum membrane and
      is assumed to be a multifunctional protein. However, detailed structure
      information is missing. The hydrophobic nature of NS4B is a major difficulty for
      many experimental techniques. We applied bioinformatics methods to analyse
      structural and functional properties of NS4B in different viruses. We distinguish
      a central non-globular membrane portion with four to five transmembrane regions
      from an N- and C-terminal part with non-transmembrane helical elements. We
      demonstrate high similarity in sequence and structure for the C-terminal part
      within the flaviviridae family. A palmitoylation site contained in the C-terminal
      part of HCV is equally conserved in GB virus B. Furthermore, we identify and
      characterize an N-terminal basic leucine zipper (bZIP) motif in HCV, which is
      suggestive of a functionally important interaction site. In addition, we model
      the interaction of the bZIP region with the recently identified interaction
      partner CREB-RP/ATF6beta, a human activating transcription factor involved in ER
      stress. In conclusion, the versatile structure, together with functional sites
      and motifs, possibly enables NS4B to adopt a role as protein hub in the
      membranous web interaction network of virus and host proteins. Important
      structural and functional properties of NS4B are predicted with implications for
      ER-stress response, altered gene expression and replication efficacy.

PMID- 17507274
TI  - Characterization and expression during development and under environmental stress
      of the genes encoding ribosomal proteins L11 and L13 in Chironomus riparius.
AB  - The Chironomus riparius gene sequences encoding ribosomal proteins L11 and L13
      were characterized and their expression analysed during development, and under
      different types of cellular stress. A comparative and phylogenetic study among
      different orders of insects was carried out by analysis of sequence databases.
      L11 is highly conserved, both at the level of DNA and protein, and it shares over
      90% amino acid identity with homologous sequences from other insects.
      Interestingly, the changes are mainly concentrated in the C-terminal domain of
      the protein. Conversely, L13 shows a lower degree of homology, around 60% amino
      acid identity, and the changes were dispersed throughout the length of the
      polypeptide. Surprisingly, when comparing L13 nucleotide sequences, only a very
      low or no homology was found even among diptera. These results are helpful for
      defining the structural and, therefore, evolutionary constraints of these
      proteins. Studies of gene expression by RT-PCR showed that they are
      differentially expressed in distinct stages of development. Both L11 and L13 were
      significantly upregulated during embryogenesis. The expression profiles of the
      transcripts were also analysed after a general stress, such as heat shock, as
      well as after a specific stress, such as acute cadmium treatment. In both
      conditions, no significant differences to controls were detected in L11 and L13
      transcripts, in spite of the drastic changes observed in the stress-induced gene
      HSP70, and the inhibitory effect on rRNA transcription. These data confirm that
      both genes are equally robust against harmful environmental conditions,
      suggesting that they could be used as a control for environmentally responsive
      genes in Chironomus. Overall, our results show a coordinated expression of both
      the L11 and the L13 genes, but not a coordinated regulation of rRNA and ribosomal
      protein production.

PMID- 17507275
TI  - Prevalence of feline chronic gingivo-stomatitis in first opinion veterinary
      practice.
AB  - Feline chronic gingivo-stomatitis (FCGS) is a syndrome characterised by
      persistent, often severe, inflammation of the oral mucosa. In the absence of
      similar studies, our objective was to estimate the prevalence of FCGS in a
      convenience based sample of cats visiting first opinion small animal veterinary
      practices. Twelve practices took part, providing a sample population of 4858
      cats. Veterinary surgeons identified cases of FCGS according to our case
      definition over a 12-week sampling period; age, sex and breed information was
      determined for all cats, plus brief descriptive data for FCGS cases. The
      prevalence of FCGS was 0.7% (34 cases, 95% confidence intervals: 0.5-1.0%). Of
      the 34 cases of FCGS, 44% (15 cats) were new cases and 56% (19 cats) were ongoing
      cases. No statistically significant difference (P>0.353) was found when the age,
      sex and breed of cats with FCGS were compared to data from cats without the
      condition.

PMID- 17507276
TI  - [Should man's age be a limiting factor in the ART management of the infertile
      couple?].

PMID- 17507277
TI  - [Unilateral partial deferential agenesia and CFTR gene composite heterozygoty
      (deltaF508/V938G)].
AB  - This is a case report of a thirty-year-old-man consulting for a primary
      infertility that was diagnosed four years ago. Andrologic exam was normal. Two
      spermograms found normal spermatic parameters. An uro-genital echography with a
      RMI showed that a unilateral agenesia of the left vas deferens in the pelvic
      portion. Then, a composite heterozygoty of the CFTR gene (DeltaF508/V938G) was
      found. This is the first time that the association of these two mutations has
      been described. This case also makes it possible to wonder about the need for
      realizing, or not, a systematic basis imagery (ultrasound examination in first),
      in the event of infertility of the couple. In this context, the discovery of an
      echographic anomaly made it possible to identify CFTR mutations, whose
      physiopathological implication in the infertility can be discussed (CFTR related
      disorders)...

PMID- 17507278
TI  - Sonochemical synthesis of amorphous nanoscopic iron(III) oxide from Fe(acac)3.
AB  - Amorphous nanoscopic iron(III) oxide with interesting magnetic properties was
      prepared by sonolysis of Fe(acac)(3) under Ar in tetraglyme with a small amount
      of added water. The organics content and the surface area of the Fe(2)O(3)
      nanoparticles can be controlled with an amount of water in the reaction mixture
      and it increases from 48 m(2)g(-1) for dry solvent up to 260 m(2)g(-1) when wet
      Ar is employed. For further monitoring of the particle size and morphology and
      for the study of the surface, magnetic and thermal properties, the sample with 2
      vol.% of H(2)O was chosen. SEM showed nanoscopic composite particles of a uniform
      size distribution and nearly spherical shapes with an estimated diameter of 20
      nm. Such composites are built from amorphous iron(III) oxide nanoparticles (3 nm)
      embedded in an acetate matrix as proved by TEM and IR spectroscopy. Temperature
      dependent Mossbauer spectra demonstrate a very narrow magnetic transition with an
      unusually low transition temperature around 25K reflecting the system of
      magnetically non-interacting ultrasmall particles with a narrow size
      distribution. The in-field (5T) Mossbauer spectrum recorded at 5K shows a minimum
      change compared to the zero-field spectrum indicating an absence of the long
      range magnetic ordering. The composite particles are thermally stable up to 150
      degrees C, which is confirmed by DSC, TG, and by the constant surface area. At
      higher temperatures, acetate groups are removed from the particle surface, which
      is documented by the increased surface area and disappearance of their IR bands.

PMID- 17507279
TI  - Signals, pathways and splicing regulation.
AB  - Alternative splicing of messenger RNA precursors is an extraordinary source of
      protein diversity and the regulation of this process is crucial for diverse
      cellular functions in both physiological and pathological situations. For many
      years, several signaling pathways have been implicated in alternative splicing
      regulation. Recent work has begun to unravel the molecular mechanisms by which
      extracellular stimuli activate signaling cascades that modulate the activity of
      the splicing machinery and therefore the splicing pattern of many different
      target messenger RNA precursors. These experiments are revealing unexpected
      aspects of the mechanism that control splicing and the consequences of the
      regulated splicing events. We summarize here the current knowledge about signal
      induced alternative splicing regulation of Slo, NR1, CD44, CD45 and fibronectin
      genes, and also discuss the importance of some of these events in determination
      of cellular fate. Furthermore, we highlight the relevance of signal-induced
      changes in phosphorylation state and subcellular distribution of splicing factors
      as a way of regulating the splicing process. Lastly, we explore new and
      unexpected findings about regulated splicing in anucleated cells.

PMID- 17507281
TI  - Surface morphology of contact lenses probed with microscopy techniques.
AB  - The present study is bringing a comparison of surface morphology for various
      types of contact lenses. A novel method--scanning electron microscopy under
      aqueous conditions (cryo-SEM)--was tested for visualization of lenses at
      magnifications up to 2000x. For imaging lens surface on nanometre scale, we
      employed atomic force microscopy (AFM) in aqueous media. Various materials of
      lenses, based on silicone hydrogels or conventional hydrogels, were investigated.
      Total, 10 types of contact lenses from five manufacturers were selected and
      probed. We found that different methods of lens manufacture (lathe-cutting, cast
      moulding, and spin casting) led to different values of surface roughness. In the
      swollen state, roughness values of lens surfaces lie between 4 and 140 nm. Lenses
      manufactured by lathe-cutting exhibit notable higher values, so that they could
      be easily distinguished from others. In cast-moulded lenses, the surface
      roughness decreased with increasing water content. Moreover, additional
      treatments of lenses introduced unique structural motifs onto surface. For
      instance, porous structure was found on lens surface finalized with plasma
      oxidation.

PMID- 17507280
TI  - The emerging role of adipokines as mediators of inflammation and immune
      responses.
AB  - Interest in the biology of white adipose tissue (WAT) has increased dramatically
      since the discovery of leptin in 1994. The identification of the product of the
      gene obese (ob) threw light on the role of adipose tissue in the physiopathology
      of obesity-related diseases, and spurred the identification of numerous other
      adipokines, many of a pro-inflammatory nature. It has become increasingly evident
      that WAT-derived cytokines mediate between obesity-related exogenous factors
      (nutrition and lifestyle) and the molecular events that lead to metabolic
      syndrome and inflammatory and/or autoimmune conditions. Here, we review recent
      adipokine research, with particular attention to the roles of leptin,
      adiponectin, resistin, visfatin, apelin, vaspin and hepcidin in such conditions.

PMID- 17507282
TI  - Genotoxic effect and nitrative DNA damage in HepG2 cells exposed to aristolochic
      acid.
AB  - Aristolochic acid (AA), extensively used as a traditional herbal medicine, was
      withdrawn from the market in the last century because it was found to be a potent
      carcinogen in humans and animals. The aim of this study was to evaluate the
      genotoxic effect of AA and obtain further insight into whether the nitrative DNA
      damage can be induced by reactive nitrogen species (RNS), including nitric oxide
      (NO) and its derivative peroxynitrite (ONOO(-)) using human hepatoma HepG2 cells.
      To identify the genotoxic effect, the comet assay and micronucleus test (MNT)
      were performed. In the comet assay, 25-200microM of AA caused a significant
      increase of DNA migration in a dose-dependent manner. A significant increase of
      the frequency of micronuclei was found in the range between 12.5 and 50microM in
      the MNT. The results showed that AA caused DNA and chromosome damages. To
      elucidate the nitrative DNA damage mechanism, the level of nitrite and 8
      hydroxydeoxyguanosine (8-OHdG), which can be generated by ONOO(-), were monitored
      with the 2,3-diaminonaphthalene (DAN) assay and immunoperoxidase staining,
      respectively. The results showed that AA causes a significant increase in the
      levels of NO and formation of 8-OHdG at concentrations >/=50microM. This
      observation supports the assumption that AA could exert genotoxicity probably via
      NO and its derivatives at higher concentrations in HepG2 cells.

PMID- 17507283
TI  - In vivo Comet assay on isolated kidney cells to distinguish genotoxic carcinogens
      from epigenetic carcinogens or cytotoxic compounds.
AB  - The objective of this study was to determine the ability of the alkaline in vivo
      Comet assay (pH>13) to distinguish genotoxic carcinogens from epigenetic
      carcinogens when performed on freshly isolated kidney cells and to determine the
      possible interference of cytotoxicity by assessing DNA damage induced by renal
      genotoxic, epigenetic or toxic compounds after enzymatic isolation of kidney
      cells from OFA Sprague-Dawley male rats. The ability of the Comet assay to
      distinguish (1) genotoxicity versus cytotoxicity and (2) genotoxic versus non
      genotoxic (epigenetic) carcinogens, was thus investigated by studying five known
      genotoxic renal carcinogens acting through diverse mechanisms of action, i.e.
      streptozotocin, aristolochic acids, 2-nitroanisole, potassium bromate and
      cisplatin, two rodent renal epigenetic carcinogens: d-limonene and ciclosporine
      and two nephrotoxic compounds: streptomycin and indomethacin. Animals were
      treated once with the test compound by the appropriate route of administration
      and genotoxic effects were measured at the two sampling times of 3-6 and 22-26h
      after treatment. Regarding the tissue processing, the limited background level of
      DNA migration observed in the negative control groups throughout all experiments
      demonstrated that the enzymatic isolation method implemented in the current study
      is appropriate. On the other hand, streptozotocin, 20mg/kg, used as positive
      reference control concurrently to each assay, caused a clear increase in the mean
      Olive Tail Moment median value, which allows validating the current methodology.
      Under these experimental conditions, the in vivo rodent Comet assay demonstrated
      good sensitivity and good specificity: all the five renal genotoxic carcinogens
      were clearly detected in at least one expression period either directly or
      indirectly, as in the case of cisplatin: for this cross-linking agent, the
      significant decrease in DNA migration observed under standard electrophoresis
      conditions was clearly amplified when the duration of electrophoresis was
      increased up to 40min. In contrast, epigenetic and nephrotoxic compounds failed
      to induce any signifcant increase in DNA migration. In conclusion, the in vivo
      rodent Comet assay performed on isolated kidney cells could be used as a tool to
      investigate the genotoxic potential of a test compound if neoplasic/preneoplasic
      changes occur after subchronic or chronic treatments, in order to determine the
      role of genotoxicity in tumor induction. Moreover, the epigenetic carcinogens and
      cytotoxic compounds displayed clearly negative responses in this study. These
      results allow excluding a DNA direct-acting mechanism of action and can thus
      suggest that a threshold exists. Therefore, the current in vivo rodent Comet
      assay could contribute to elucidate an epigenetic mechanism and thus, to
      undertake a risk assessment associated with human use, depending on the exposure
      level.

PMID- 17507284
TI  - Antioxidant activity of diphenyl diselenide prevents the genotoxicity of several
      mutagens in Chinese hamster V79 cells.
AB  - Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a
      variety of pharmacologically active organic selenium compounds. Studies have
      shown its antioxidant, hepatoprotective, neuroprotective, anti-inflammatory, and
      antinociceptive effects. We recently showed the antioxidant effect of DPDS in V79
      cells, and established the beneficial and toxic doses of this compound in this
      cell line. Here, we report the antigenotoxic and antimutagenic properties of
      DPDS, investigated by using a permanent lung fibroblast cell line derived from
      Chinese hamsters. We determined the cytotoxicity by clonal survival assay, and
      evaluated DNA damage in response to several mutagens by comet assay and
      micronucleus test in binucleated cells. In the clonal survival assay, at
      concentrations ranging from 1.62 to 12.5microM, DPDS was not cytotoxic, while at
      concentrations up to 25microM, it significantly decreased survival. The treatment
      with this organoselenium compound at non-cytotoxic dose range increased cell
      survival after challenge with hydrogen peroxide, methyl-methanesulphonate, and
      UVC radiation, but did not protect against 8-methoxypsoralen plus UVA-induced
      cytotoxicity. In addition, the treatment prevented induced DNA damage, as
      verified in the comet assay. The mutagenic effect of these genotoxins, as
      measured by the micronucleus test, similarly attenuated or prevented cytotoxicity
      and DNA damage. Treatment with DPDS also decreased lipid peroxidation levels
      after exposure to hydrogen peroxide MMS, and UVC radiation, and increased
      glutathione peroxidase activity in the extracts. Our results clearly demonstrate
      that DPDS at low concentrations presents antimutagenic properties, which are most
      probably due to its antioxidant properties.

PMID- 17507285
TI  - Vibrational spectra and ab initio analysis of tert-butyl, trimethylsilyl,
      trimethylgermyl, trimethylstannyl, and trimethylplumbyl derivatives of 3,3
      dimethylcyclopropene X. Some regularities.
AB  - The changes in the vibrational frequencies of 1-tert-butyl and 1,2-di-tert-butyl
      derivatives of 3,3-dimethylcyclopropene brought about by substitution of the
      central carbon atom (X) of the tert-butyl moieties by Si, Ge, Sn, or Pb atoms are
      examined. The most important decrease in the vibrational frequencies implicating
      the X(CH(3))(3) moieties is noted for substitution of X=C by Si. The
      substitutions of Si by Ge or Ge by Sn or Sn by Pb are not accompanied by the
      pronounced frequency shifts observed for the C-->Si transition. An explanation is
      given for trends in these vibrational frequencies for the transitions X=C-->Si-
      >Ge-->Sn-->Pb. It is concluded that there are lower limiting values of the
      vibrational frequencies of a molecular moiety which are approached when the mass
      of its isovalent atom is increased. This leads to the formation of cluster
      regions in the vibrational spectra for the frequencies of the SnC(3) and PbC(3)
      moieties.

PMID- 17507286
TI  - The differences of clinical manifestations and laboratory findings in children
      and adults with dengue virus infection.
AB  - BACKGROUND: Dengue haemorrhagic fever is an important public health problem and
      mainly occurs in children less than 15 years of age. Recently, the incidence of
      the disease have increased in adults but data on clinical and laboratory
      presentations of those affected are limited. OBJECTIVES: To assess and compare
      clinical manifestations and laboratory findings of dengue virus infected children
      and adults in Thailand. STUDY DESIGN: A 1-year study was conducted from September
      2003 to August 2004 for dengue virus infected patients admitted to Phetchabun
      Provincial Hospital, Thailand. Physical signs, symptoms, and laboratory features
      were recorded. All dengue patients were confirmed using immunochromatographic
      test on convalescent sera. RESULTS: Based on serology-confirmed dengue virus
      infection, there was 286 dengue patients including 15 (5.3%) dengue fever and 271
      (94.7%) dengue haemorrhagic fever (DHF). Among DHF cases, clinical
      classifications were DHF I, 40.9%; DHF II, 43%; and DHF III or dengue shock
      syndrome (DSS), 10.8%. Of all dengue patients, 231 cases (80.8%) were children
      aged less than 15 years and 55 cases (19.2%) were adults. The highest proportion
      of child cases was DHF I (42.9%), whereas that of adults was DHF II (51%). Some
      clinical manifestations were more common in adult patients, such as petechiae,
      melena, headache, retro-orbital pain, joint pain, myalgia, nausea and vomiting (p
      value<0.05). Signs found commonly in children were epistaxis, oliguria, and liver
      enlargement (p-value<0.05). Haemoconcentration, thrombocytopenia, increased
      alanine aminotransferase, and longer prothrombin time were found to be
      significantly higher in adults than in children (p-value<0.05). CONCLUSIONS: Some
      clinical presentations of dengue disease and laboratory findings in adults are
      different from those in children. Therefore, adults as well as pediatric cases of
      DHF need appropriate and prompt case management to reduce the mortality rate of
      DHF.

PMID- 17507287
TI  - Miniaturized, on-head, invasive electrode connector integrated EEG data
      acquisition system.
AB  - OBJECTIVE: Intracranial electroencephalogram (EEG) monitoring involves recording
      multi-contact electrodes. The current systems require separate wires from each
      recording contact to the data acquisition unit resulting in many connectors and
      cables. To overcome limitations of such systems such as noise, restrictions in
      patient mobility and compliance, we developed a miniaturized EEG monitoring
      system with the amplifiers and multiplexers integrated into the electrode
      connectors and mounted on the head. METHODS: Small, surface-mounted
      instrumentation amplifiers, coupled with 8:1 analog multiplexers, were assembled
      into 8-channel modular units to connect to 16:1 analog multiplexer manifold to
      create a small (55 cm(3)) head-mounted 128-channel system. A 6-conductor, 30 m
      long cable was used to transmit the EEG signals from the patient to the remote
      data acquisition system. RESULTS: Miniaturized EEG amplifiers and analog
      multiplexers were integrated directly into the electrode connectors. Up to 128
      channels of EEG were amplified and analog multiplexed directly on the patient's
      head. The amplified EEG data were obtained over one long wire. CONCLUSIONS: A
      miniaturized system of invasive EEG recording has the potential to reduce
      artefact, simplify trouble-shooting, lower nursing care and increase patient
      compliance. SIGNIFICANCE: Miniaturization technology improves intracranial EEG
      monitoring and leads to >128-channel capacity.

PMID- 17507288
TI  - Transcranial electric stimulation for intraoperative motor evoked potential
      monitoring: Stimulation parameters and electrode montages.
AB  - OBJECTIVE: To evaluate the efficacy of constant current transcranial electric
      stimulation (TES) parameters for eliciting muscle motor evoked potentials (MEPs)
      in the abductor pollicis brevis muscles (APB) and the tibialis anterior muscles
      (TA). The following parameters were tested intraoperatively: interstimulus
      interval (ISI), individual stimulation pulse duration within a train of five
      stimuli. Different montages of stimulating electrodes were assessed for
      effectiveness and focality. Further, reference values for APB and TA motor
      thresholds in neurosurgical patients with normal motor status under total
      intravenous anesthesia were determined. METHODS: Motor thresholds of
      contralateral muscle MEPs were determined at 0.1, 0.2, 0.4, and 0.5 ms pulse
      duration and ISIs of 2, 3, 4, and 5 ms using a train of five monophasic constant
      current pulses with C3/C4 (27 patients). The stimulating electrodes were
      positioned at C1, C2, C3, C4, Cz, and Cz+6 cm. Different montages were used to
      determine the most effective and the most focal stimulation montages for the APB
      and TA muscles (30 patients). Eighty-six patients with clinically normal motor
      function were studied for motor threshold reference values. RESULTS: The
      prolongation of the pulse duration has the strongest effect to decrease the motor
      threshold, which proportionally increases the delivered charge. The lowest
      stimulation threshold to elicit muscle MEPs in the APB and TA muscles is achieved
      with a train of stimuli consisting of an individual stimulus pulse duration of
      0.5 ms. An ISI of 4 ms gave the lowest motor thresholds, but did not reach
      statistical significance compared to 3 ms. The stimulating electrode montage
      C3/C4 (C4/C3) allows for the lowest stimulation thresholds, but the vigorous
      muscle contractions it has is a disadvantage. The most focal stimulating
      electrode montages for the contralateral APB muscles are C3/Cz and C4/Cz,
      respectively, and for the TA muscles Cz/Cz+6 cm. CONCLUSIONS: In adult
      neurosurgical patients with a normal motor status under total intravenous
      anesthesia, an individual pulse duration of 0.5 ms and an ISI of 4 ms provide the
      lowest motor thresholds. Pragmatically, C1/C2, resp., C2/C1 montage provides
      monitorable responses in both APB and TA muscles at reasonable stimulation
      thresholds without inducing movements disturbing surgery and especially
      microdissection. If the most focal hemispheric stimulation for the distal upper
      extremity muscles is required, the use of C3 or C4 referenced to Cz is
      recommended. SIGNIFICANCE: The stimulation parameters within a train of five
      pulses with an individual pulse duration of 0.5 ms and an ISI of 4 ms provide the
      lowest motor threshold. These data confirm not only studies for D wave recovery
      but also provide optimal stimulation parameters for intraoperative near threshold
      stimulation.

PMID- 17507289
TI  - Single-fiber electromyography in sporadic inclusion body myopathy.
AB  - OBJECTIVE: To report the SFEMG findings in sporadic inclusion body myopathy (S
      IBM). METHODS: We have analyzed the SFEMG data in 25 patients (mean age: 63; 16
      males) with S-IBM which was diagnosed by the presence of classical rimmed
      vacuoles in the muscle biopsy together with clinical, laboratory, and
      electrophysiological findings. RESULTS: All patients had fibrillations, positive
      sharp waves, and small-amplitude short-duration motor unit potentials (MUPs) in
      the needle EMG. High-amplitude MUPs were observed in eight (32%) patients, two of
      whom had long-duration MUPs. SFEMG was abnormal in 17 (68%) cases: mean "mean
      consecutive difference (MCD)" was increased beyond the age-adjusted normal limit
      in 16 cases, and more than 10% of potential pairs (PP) had MCD longer than the
      upper normal limit of an individual MCD in one case. Mean fiber density (FD) was
      2.16, with maximum FD being 4.15. Increased FD was noted in 11 (44%) cases. In
      four cases, more than 10% of PP had blocking, but there was no neurogenic
      blocking in any PP. As expected, MCD increased linearly (r=0.85) with the
      percentage of PP beyond the normal upper limit. CONCLUSIONS: The SFEMG findings
      in S-IBM are typical of the classical pattern of myopathy. SIGNIFICANCE: Our
      findings support the consensus that S-IBM is a myopathy.

PMID- 17507290
TI  - Does age worsen EEG slowing and attention deficits in obstructive sleep apnea
      syndrome?
AB  - OBJECTIVE: The aim of this study was to determine whether EEG slowing is more
      pronounced in older than younger OSAS patients and to verify whether this
      cortical slowing is correlated to daytime performance, respiratory perturbation
      and sleep fragmentation. METHODS: Twelve young OSAS patients (mean age 38.2+/-2.0
      y) and 13 older OSAS patients (mean age 62.2+/-1.9 y) along with 13 young
      controls (mean age 35.8+/-2.0 y) and 14 older controls (mean age 60.2+/-2.0 y)
      underwent a polysomnographic evaluation followed by a waking EEG recording. As a
      global index of cortical slowing, a ratio of slow-to-fast frequencies was
      calculated in all cortical regions. Daytime performance was assessed using the
      four choice reaction time test. RESULTS: Differences in waking EEG and in daytime
      performance were analyzed by ANOVAs with Group and Age as factors. Waking EEG did
      not yield a Group by Age interaction. OSAS patients had higher ratios across all
      regions than controls. Similarly, daytime performance revealed no Group by Age
      interaction. However, OSAS patients showed more lapses than controls and older
      subjects were slower than younger subjects. CONCLUSIONS: Our results indicate
      that age does not interact with OSAS to worsen the severity of cortical slowing,
      but age can add to the OSAS effect to worsen daytime performance deficits in OSAS
      patients. SIGNIFICANCE: The daytime performance deficits observed particularly in
      elderly OSAS patients warrant a careful clinical assessment of these patients to
      prevent accidents and injuries.

PMID- 17507291
TI  - Depression of the human nociceptive withdrawal reflex by segmental and
      heterosegmental intramuscular electrical stimulation.
AB  - OBJECTIVE: To investigate the effects of intramuscular electrical conditioning in
      the modulation of nociceptive withdrawal reflex (NWR) and further to determine
      what muscle afferents are involved in the modulation of the nociceptive
      withdrawal reflex and the sites along the reflex pathway where the NWR modulation
      occurs in healthy humans. METHODS: The NWR elicited by a cutaneous test stimulus
      to the dorsal foot was modulated by a short (21 ms) intramuscular conditioning
      electrical stimulus at two times the pain threshold. At varying conditioning-test
      stimulus intervals, segmental conditioning stimulus was applied in the tibialis
      anterior muscle ipsilateral and contralateral to the test stimulus, and
      heterosegmental conditioning stimulus was applied in the contralateral trapezius
      muscle to modulate the NWR. Non-painful and painful intramuscular conditioning
      stimuli were also used to modulate the NWR and the soleus H-reflex. RESULTS: The
      NWR was depressed by preceding intramuscular conditioning stimuli, with a degree
      that depended on the conditioning-test stimulus intervals and on the conditioning
      site. Segmental conditioning depressed the NWR more quickly and gave a longer
      duration (15-1500 ms), and larger magnitude than heterosegmental conditioning,
      which depressed the NWR in a short temporal window (80-100 ms). No difference was
      seen in the magnitude of the NWR depression between the painful and non-painful
      intramuscular stimuli, and the soleus H-reflex was not affected. CONCLUSIONS: Our
      results suggest that segmental and heterosegmental conditionings of NWR are
      mediated by myelinated muscle afferents engaging central inhibitory mechanisms
      rather than direct changes in the excitability of motor neurons. SIGNIFICANCE:
      The therapeutic effects of electrotherapy could involve these mechanisms in the
      treatment of muscle pain syndromes.

PMID- 17507292
TI  - Patient safety: not just another bandwagon.

PMID- 17507293
TI  - Contribution of supraspinal and spinal structures to the responses of dorsal
      spinal cord blood flow to innocuous cutaneous brushing in rats.
AB  - Responses of dorsal spinal cord blood flow (SCBF) to innocuous mechanical
      cutaneous stimulation were investigated in anesthetized central nervous system
      intact (CNS-intact) and C2 spinalized rats. SCBF was recorded at the L4-L6 level
      with a laser Doppler flowmeter. SCBF increased with brushing of the ipsilateral
      proximal hindlimb and hindpaw, and there were no significant differences in the
      magnitudes of the responses in CNS-intact and spinalized animals. Brushing of the
      lower back had no effect on SCBF at the L4-L6 level in either cohort. Brushing
      stimulation produced no significant changes in systemic arterial blood pressure.
      The responses of SCBF to brushing in CNS-intact animals were diminished by
      pretreatment with phenoxybenzamine, an alpha-adrenoceptor blocking agent, but no
      such effects were seen in spinalized animals. These results indicate that
      innocuous mechanical cutaneous input can produce a segmentally-organized increase
      in regional SCBF, and that the responses are modulated, in part at least, by
      alpha-adrenergic receptors via supraspinal structures.

PMID- 17507294
TI  - Sympathetic nerve traffic and circulating norepinephrine levels in RGS2-deficient
      mice.
AB  - Regulator of G protein signaling 2 (RGS2-/-) deficient mice feature an increased
      resting blood pressure and an excessive pressor response to stress. We measured
      renal sympathetic nerve activity (RSNA) directly to test the hypothesis that RSNA
      is increased in RGS2-/- mice, compared to RGS2+/+ mice. Seventeen mice (RGS2-/-,
      n=9; RGS2+/+, n=8) were anesthetized with isoflurane. We cannulated the left
      jugular vein for drug administration. Renal sympathetic nerve activity (RSNA) was
      recorded using bipolar electrodes. Arterial blood pressure (BP) from the femoral
      artery, ECG (needle electrodes), and RSNA were recorded (sample rate 10 kHz)
      simultaneously. RSNA was analysed off-line using a modified wavelet de-noising
      technique and the classical discriminator method. RSNA detected during
      phenylephrine bolus injections or after the animals death was subtracted from
      baseline values. Mean arterial blood pressure, norepinephrine plasma levels, the
      responsiveness to vasoactive drugs, and the sympathetic baroreflex gain were
      similar in anesthetized RGS2+/+ and RGS2-/- animals. RSNA was lower in RGS2-/-
      mice compared to wild-type controls (wavelet: spike rate in Hz: RGS2+/+ 25.5+/
      5.1; RGS2-/- 17.4+/-4.0; discriminator method: RGS2+/+ 41.4+/-5.7, RGS2-/- 22.0+/
      4.3, p<0.05). Thus, the expected result proved not to be the case. Our data
      suggest a mismatch between sympathetic nerve traffic and plasma norepinephrine
      concentrations. This observation may depend on altered coupling between
      electrical nerve activity and norepinephrine release and/or a changed
      norepinephrine uptake in RGS2-/- mice.

PMID- 17507295
TI  - Methylation damage response in hematopoietic progenitor cells.
AB  - The cellular response to methylation DNA damage was compared in multipotent
      CD34(+) hematopoietic stem cells and mature CD34(-) cells isolated from cord
      blood of the same donor. Cytofluorimetric analysis of freshly isolated cord blood
      cells indicated that both cell types were in the G0/G1 phase of the cell cycle.
      Quantitative RT-PCR identified a general trend towards high expression of several
      DNA repair genes in CD34(+) cells compared to their terminally differentiated
      CD34(-) counterparts. The overexpressed genes included members of the mismatch
      repair (MMR) (MSH2, MSH6, MLH1, PMS2), base excision repair (AAG, APEX), DNA
      damage reversal (O(6)-methylguanine DNA methyltransferase) (MGMT), and DNA double
      strand breaks repair pathways. These differences in gene expression were not
      apparent in CD34(+) and CD34(-) cells obtained following expansion of CD34(+)
      cells in a medium containing early acting cytokines. Early progenitor CD34(+) and
      early precursor CD34(-) cells form the two populations isolated under these
      experimental conditions, and both contain a significant proportion of cycling
      cells. The methylating agent N-methyl-N-nitrosourea (MNU) induced similar levels
      of apoptosis in these cycling CD34(+) and CD34(-) cells. Cytotoxicity required
      the presence of the MGMT inhibitor O(6)-benzylguanine and the timing of MNU cell
      death (48 and 72h) was similar in CD34(+) and CD34(-) cells. These data indicate
      that cycling CD34(+) and CD34(-) cells are equally sensitive to methylation
      damage. MGMT provides significant protection against MNU toxicity and MGMT and
      MMR play the expected roles in the MNU sensitivity of these cells.

PMID- 17507297
TI  - Partial within-animal calibration: a new calibration approach in lead
      optimisation high-throughput bioanalysis.
AB  - The lead optimization phase of drug discovery requires high-throughput analyses
      for quantification in biological matrices and in plasma in particular. Over the
      last decade, some technical innovations allowed the pharmaceutical industry to
      improve the quality of the results. However, there is room for improvement. In
      this context, a new calibration strategy is proposed in this paper. Experiments
      were performed on dog plasma samples and it was showed that a within-animal
      calibration strategy can reduce the bias up to 20% and improve the precision up
      to 20%. However, a partial within-animal calibration is preferred to the full
      approach in order to avoid to many sample preparations.

PMID- 17507298
TI  - Neighborhood context and ethnicity differences in body mass index: a multilevel
      analysis using the NHANES III survey (1988-1994).
AB  - A growing body of literature has documented a link between neighborhood context
      and health outcomes. However, little is known about the relationship between
      neighborhood context and body mass index (BMI) or whether the association between
      neighborhood context and BMI differs by ethnicity. This paper investigates
      several neighborhood characteristics as potential explanatory factors for the
      variation of BMI across the United States; further, this paper explores to what
      extent segregation and the concentration of disadvantage across neighborhoods
      help explain ethnic disparities in BMI. Using data geo-coded at the census tract
      level and linked with individual-level data from the Third National Health and
      Examination Survey in the United States (U.S.), we find significant variation in
      BMI across U.S. neighborhoods. In addition, neighborhood characteristics have a
      significant association with body mass and partially explain ethnic disparities
      in BMI, net of individual-level adjustments. These data also reveal evidence that
      ethnic enclaves are not in fact advantageous for the body mass index of Hispanics
      a relationship counter to what has been documented for other health outcomes.

PMID- 17507299
TI  - Serum proteomic-based analysis of pancreatic carcinoma for the identification of
      potential cancer biomarkers.
AB  - To identify new biomarkers that improve the early diagnosis and lead to possible
      therapeutic targets in pancreatic carcinoma, we performed a proteomic approach to
      compare serum protein expression patterns of pancreatic carcinoma patients with
      that of gastric cancer patients, other pancreatic disease patients, and healthy
      volunteers. By two-dimensional gel electrophoresis (2-DE) analyses and mass
      spectroscopic identification, 10 protein spots were found significantly changed
      in pancreatic carcinoma and 5 proteins including cyclin I, Rab GDP dissociation
      inhibitor beta (GDI2), alpha-1 antitrypsin precursor, Haptoglobin precursor, and
      Serotransferrin precursor were successfully identified. The increased levels of
      cyclin I and GDI2 found to be associated with pancreatic carcinoma were further
      confirmed by Western blot analyses in an independent series of serum samples
      and/or pancreatic juice samples. Applying immunohistochemistry, we further
      validated expression of cyclin I and GDI2 in additional pancreatic carcinomas.
      These results indicate that cyclin I and GDI2 may be potential molecular targets
      for pancreatic cancer diagnostics and therapeutics.

PMID- 17507300
TI  - A biodegradable vascularizing membrane: a feasibility study.
AB  - Regenerative medicine and in vivo biosensor applications require the formation of
      mature vascular networks for long-term success. This study investigated whether
      biodegradable porous membranes could induce the formation of a vascularized
      fibrous capsule and, if so, the effect of degradation kinetics on
      neovascularization. Poly(l-lactic acid) (PLLA) and poly(dl-lactic-co-glycolic)
      acid (PLGA) membranes were created by a solvent casting/salt leaching method.
      Specifically, PLLA, PLGA 75:25 and PLGA 50:50 polymers were used to vary
      degradation kinetics. The membranes were designed to have an average 60mum pore
      diameter, as this pore size has been shown to be optimal for inducing blood
      vessel formation around nondegradable polymer materials. Membrane samples were
      imaged by scanning electron microscopy at several time points during in vitro
      degradation to assess any changes in pore structure. The in vivo performance of
      the membranes was assessed in Sprague-Dawley rats by measuring vascularization
      within the fibrous capsule that forms adjacent to implants. The vascular density
      within 100microm of the membranes was compared with that seen in normal tissue,
      and to that surrounding the commercially available vascularizing membrane
      TheraCyte. The hemoglobin content of tissue containing the membranes was measured
      by four-dimensional elastic light scattering as a novel method to assess tissue
      perfusion. Results from this study show that slow-degrading membranes induce
      greater amounts of neovascularization and a thinner fibrous capsule relative to
      fast degrading membranes. These results may be due both to an initially increased
      number of macrophages surrounding the slower degrading membranes and to the
      maintenance of their initial pore structure.

PMID- 17507302
TI  - In response to 'A late complication following the insertion of hydrogel breast
      implants'.

PMID- 17507303
TI  - The posterior interosseous flap - a prime technique in hand reconstruction. The
      experience of 100 anatomical dissections and 102 clinical cases.
AB  - Based on our experience of 102 clinical cases and 100 anatomical dissections, we
      have assessed the indications for the posterior interosseous flap in
      reconstruction of the hand. Large fasciocutaneous island flaps can be harvested,
      even when the radial or ulnar pedicles are damaged. One real advantage is that
      the posterior interosseous artery is a vessel of secondary importance for hand
      vascularisation. Fasciocutaneous and osteofasciocutaneous island distally based
      flaps can be tailored. The major indications are reconstruction of the first web
      space up to the interphalangeal joint of the thumb, dorsal hand defects up to the
      metacarpal joints and large defects on the palm-ulnar border of the hand. It is,
      therefore, a primary weapon amongst hand reconstruction techniques.

PMID- 17507304
TI  - Salvage of infected breast expander prosthesis: the advantage of an integral
      port.

PMID- 17507305
TI  - Abdominoplasty as an adjunct to the management of peri-Caesarian section
      necrotising fasciitis.
AB  - Necrotising fasciitis is a rare but potentially lethal condition, often requiring
      extensive soft tissue debridement and complex reconstructive surgery. The disease
      has been noted to complicate Caesarian section wounds, and our department has
      recently managed three such patients. They all required extensive abdominal wall
      debridements which would traditionally be closed initially by split skin
      grafting. We report on the clinical course of three patients, two of whom had
      their defects closed successfully by abdominoplasty without recourse to initial
      skin grafting.

PMID- 17507306
TI  - Consensus recommendation from a group of German experts for the use of
      enfuvirtide in heavily pretreated HIV patients.
AB  - BACKGROUND: The EU approval of enfuvirtide (Fuzeon) was granted in May 2003 on
      the basis of the 48-week data from the TORO 1 and TORO 2 studies. Enfuvirtide is
      licensed for use in pretreated HIV patients experienced with three classes of
      drugs who exhibited treatment failure or who have shown intolerance to previous
      antiretroviral treatment regimens. Recent studies with the new protease
      inhibitors tipranavir and darunavir (RESIST and POWER studies) showed that a high
      proportion of heavily pretreated HIV patients achieve a viral load reduction to
      below the limit of detection when treated with enfuvirtide plus one of these new
      ritonavir-boosted protease inhibitors and an optimised background treatment
      regimen. The International AIDS Society (IAS-USA Panel) has recently updated its
      treatment guidelines in view of these new data and recommends the use of an
      antiretroviral treatment regimen containing at least two active drugs, one of
      which that has a new mechanism of action, for HIV patients who have been heavily
      pretreated. A new treatment goal has also emerged for heavily pretreated patients
      with advanced HIV disease: reduction of the viral load to below the detection
      limit of 50 copies/ml. The IAS concluded that the likelihood of achieving this
      treatment goal is higher when enfuvirtide is selected as one of the two active
      drugs. OBJECTIVE: A panel of German experts convened to discuss the currently
      available data and to incorporate them into the updated German consensus
      recommendations for the use of enfuvirtide when switching treatment in heavily
      pretreated HIV patients. METHODS: The consensus recommendations are based on
      published data from controlled, randomised clinical studies and on the expert
      opinions of the discussants. RESULTS AND CONCLUSIONS: The consensus
      recommendations were developed to provide practice-relevant standardised
      recommendations for selecting suitable candidates for enfuvirtide therapy and for
      their management. Aspects including predictive prognostic factors, disease stage,
      selection of the optimised background regimen, early indicators of a response to
      enfuvirtide, as well as accompanying educational measures treatment were
      considered. New protease inhibitors or other remaining active drugs should be
      used together with enfuvirtide in heavily pretreated patients in order to enable
      at least two active drugs to be included in such a salvage regimen.

PMID- 17507307
TI  - Complementary cancer therapy: a systematic review of prospective clinical trials
      on anthroposophic mistletoe extracts.
AB  - BACKGROUND: Anthroposophic Mistletoe therapy is a widely used complementary
      cancer treatment. OBJECTIVE: To evaluate prospective clinical trials on the
      effectiveness of anthroposophic mistletoe therapy for cancer. DESIGN: Systematic
      review. MATERIAL AND METHODS: Search of 9 electronic databases, reference lists
      and extensive expert consultations. Criteria-based assessment of methodological
      study quality. RESULTS: 16 randomized (RCT) and 9 non-randomized (N-RCT)
      controlled trials were identified that investigated mistletoe treatment of
      malignant diseases. Statistically significant benefit for survival was reported
      in 8 of 17 trials (in 5 of 10 RCTs), for disease-free survival and tumour
      recurrence in none of 2 RCTs, for remission of tumour and malignant effusion in 1
      RCT and 1 N-RCT of 4 controlled trials, for quality of life (QoL) in 3 of 5 RCTs,
      and for QoL and reduction of side effects of cytoreductive therapies
      (chemotherapy, radiation or surgery) in 5 of 7 trials (3 of 5 RCTs).
      Methodological quality of the controlled trials differed substantially; some had
      major limitations while others were reasonably well conducted. 12 single-arm
      cohort studies were identified. 5 of 7 studies found substantial tumour remission
      in various cancers, one study reported remission of CIN, and 4 studies remission
      of malignant pleural effusion or ascites. Quality of reporting in cohort studies
      was mostly reasonably good. Mistletoe application was well tolerated.
      CONCLUSIONS: Regarding quality of studies and consistency of results, the best
      evidence for efficacy of mistletoe therapy exists for improvement of QoL and
      reduction of side effects of cytotoxic therapies (chemotherapy, radiation).
      Survival benefit has been shown but not beyond critique. Tumour remissions are
      described in cohort studies that investigate the application of high dose or
      local mistletoe extracts. As several reasonably well-conducted studies indicate
      beneficial effects, further properly designed trials should be encouraged to
      investigate clinical efficacy and its possible dependency on the mode of
      application.

PMID- 17507308
TI  - Antibiotic resistance testing of the total implant-associated micro-flora and its
      pure isolates.
AB  - OBJECTIVE: The aim of the present study was to examine antibiotic resistant
      strains among the implant-associated microorganisms in vitro, first as mixed
      cultures and again as pure isolates for resistance to one of five antibiotics.
      METHODS: Samples were taken with sterile paper points from the deepest pocket of
      one implant per patient (n = 24) to culture the total oral micro-flora. The
      samples were streaked on agar (Schaedler or BHI) and incubated for 7 d in an
      anaerobic atmosphere. All colonies were rinsed off the plates, aliquots were
      added to top-agar. Susceptibility against antibiotics (ampicillin, ampicillin +
      sulbactam, azithromycin and penicillin, moxifloxacin) was determined using the
      Etest. Resistant strains were picked, purified and characterized, and the Etests
      were repeated with a selection of the pure isolates. RESULT: The majority of the
      mixed cultures (67 - 100 %) showed complete antibiotic resistance. No association
      with clinical parameters like pocket depth, bleeding on probing or insertion of
      implants into transplanted bone could be found. Smoking and the surface of the
      implant also had no influence. 23 % of the 597 resistant colonies contained only
      yeasts, mostly isolated from irradiated tumour patients. Of the 458 resistant
      bacteria, the majority were Gram-positive cocci or rods. Staphylococci and M.
      micros were detected occasionally. The resistance for the 138 selected pure
      isolates was in most cases lower than for the total micro-flora, irrespective of
      the antibiotic. CONCLUSIONS: The higher resistance of the total flora might be
      explained by synergistic interactions between its members.

PMID- 17507309
TI  - Endothelin-1 induces functionally active CD40 protein via nuclear factor-kappaB
      in human vascular smooth muscle cells.
AB  - A plethora of evidence supports a link between inflammation and atherogenesis.
      The vasoactive peptide endothelin-1 (ET-1) has both proatherogenic and
      proinflammatory properties. The CD40-CD154 signaling pathway exhibits a direct
      influence on atherogenesis. We therefore tested the hypothesis that ET-1 induces
      CD40 in human vascular smooth muscle cells (SMC). ET-1 concentration-dependently
      stimulated CD40 protein in SMC. The specific ET-A-receptor antagonist BQ-123
      prevented CD40 induction demonstrating receptor specificity of the ET-1 effect.
      Experiments with PI-1, an inhibitor of the IkappaB-a-degrading proteasome
      complex, demonstrated involvement of the transcription factor NF-kappaB in ET-1
      induced CD40 expression. Specific decoy oligodeoxynucleotides with the consensus
      binding sequence for NF-kappaB and AP-1 supported a NF-kappaB-dependent and AP-1
      independent induction pathway. Functional relevance of ET-1-induced CD40
      expression was demonstrated by an increase in IL-6 secretion after stimulation
      with CD154 of cells preactivated with ET-1. The data show a link between a
      proatherogenic vasoactive peptide and cell-cell contact mediated inflammatory
      pathways and may implicate novel therapeutic options for vascular disease.

PMID- 17507310
TI  - Two cases of severe obstructive pneumonia associated with an HKU1-like
      coronavirus.
AB  - BACKGROUND: During the last few years a number of previously undescribed viruses,
      including human metapneumovirus, coronaviruses SARS, NL63 and HKU1, and
      bocavirus, were identified in nasopharyngeal samples from patients with signs of
      respiratory infections. These viruses may cause mild to life-threatening
      infections. OBJECTIVES: Nasopharyngeal samples from hospitalized pediatric
      patients with respiratory disease were analysed for the presence of coronaviruses
      and other well known and newly identified respiratory viruses. RESULTS: Two
      clinical cases of a severe obstructive pneumonia, which were associated with the
      presence of RNA of a novel variant (subtype) of HKU1 coronavirus in the
      nasopharyngeal aspirates, were identified. DISCUSSION: The detection of a HKU1
      like coronavirus in pediatric patients in the current study complement the most
      recent independent finding of similar or closely related coronaviruses in
      patients with respiratory diseases in France (Vabret et al. 2006) and Norway
      (Jonassen et al., see accompanying manuscript). These observations indicate a
      wide dissemination of HKU1-like coronaviruses in Europe.

PMID- 17507311
TI  - Enediyne compounds - new promises in anticancer therapy.
AB  - Scientists of all kinds have long been intrigued by the nature, action and
      potential of natural toxins that possess exceptional antibacterial and anticancer
      activities. These compounds, named enediynes, are among the most effective
      chemotherapeutic agents known. Often compared with intelligent weapons, due to
      the unique structure and sophisticated mechanism by which they destroy double
      helical DNA, enediyne antibiotics are nowadays the most promising leaders in the
      anticancer therapy. Apart from their diversity, enediyne compounds share some
      structural and functional similarities. One fragment of a structure is
      responsible for the recognition and transport, another part acts as molecular
      trigger while the third, reactive enediyne unit, undergoes Bergman
      cycloaromatization and causes DNA breakage. Members of the enediyne family are
      already in clinical use to treat various cancers, but more general use is limited
      by their complex structure, which makes them formidable targets for synthetic
      chemists. There are three main approaches in the design of new enediyne-related
      compounds: improvement of enediyne >>warheads<<, increasing the selectivity and
      control of chemical or photo-induced activation. This paper gives an overview of
      naturally occurring enediynes, their mode of action and efforts undertaken to
      design artificial enediyne-related DNA cleaving agents.

PMID- 17507312
TI  - Development and evaluation of carvedilol transdermal patches.
AB  - Transdermal patches of carvedilol with a HPMC-drug reservoir were prepared by the
      solvent evaporation technique. In this investigation, the membranes of Eudragit
      RL100 and Eudragit RS100 were cast to achieve controlled release of the drug. The
      prepared patches possessed satisfactory physicochemical characteristics.
      Thickness, mass and drug content were uniform in prepared batches. Moisture
      vapour transmission through the patches followed zero-order kinetics. In vitro
      permeation studies were performed using a K-C diffusion cell across hairless
      guinea pig skin and followed the super case II transport mechanism. The effects
      of non-ionic surfactants Tween 80 and Span 80 on drug permeation were studied.
      The nonionic surfactants in the patches increased the permeation rate, Span 80
      exhibiting better enhancement relative to Tween 80. The patches were seemingly
      free of potentially hazardous skin irritation.

PMID- 17507313
TI  - Mucuna gum microspheres for oral delivery of glibenclamide: In vitro evaluation.
AB  - An investigation into the suitability of mucuna gum microspheres for oral
      delivery of glibenclamide is presented. Mucuna gum microspheres were formulated
      under different conditions of polymer concentration and crosslinking time at
      constant speed. The formulated microspheres were thereafter loaded with
      glibenclamide by the remote loading process. The microspheres were evaluated
      according to particle size, yield, loading efficiency and swelling. In vitro
      release of glibenclamide from the microspheres was studied in simulated
      intestinal fluid (SIF, pH 7.4). The release data was fitted into two release
      models to investigate the mechanism of glibenclamide release from the
      microspheres. All the microspheres showed good swelling characteristics in
      distilled water. The investigation revealed that the microspheres produced with
      5% (m/V) mucuna gum with a crosslinking time of 5 h had the optimum prolonged
      release pattern. The microspheres produced using 10% (m/V) mucuna gum with a
      crosslinking time of 1 h had the highest delayed release of the incorporated
      drug, whereas those without crosslinking had the fastest release. The Ritger
      Peppas case I transport model appeared to have adequately described the release
      process as about 54% of the batches of microspheres conformed to this model. This
      implies that a formulation of glibenclamide-loaded mucuna gum microspheres is
      likely to offer a reliable means of delivering glibenclamide by the oral route.

PMID- 17507314
TI  - Spherical crystals of celecoxib to improve solubility, dissolution rate and
      micromeritic properties.
AB  - Celecoxib spherical agglomerates were prepared with polyvinylpyrrolidone (PVP)
      using acetone, water and chloroform as solvent, non-solvent and bridging liquid,
      respectively. The agglomerates were characterized by differential scanning
      calorimetry (DSC), X-ray diffraction (XRD), IR spectroscopic studies and scanning
      electron microscopy (SEM). The IR spectroscopy and DSC results indicated the
      absence of any interactions between drug and additives. XRD studies showed a
      decrease in crystallinity in agglomerates. The crystals exhibited significantly
      improved micromeritic properties compared to pure drug. The loading efficiency (%
      or mg drug per 100 mg crystals) was in the range of 93.9 +/- 2.3 and 97.3 +/-
      1.3% (n = 3) with all formulations. The aqueous solubility and dissolution rate
      of the drug from crystals was significantly (p < 0.05) increased (nearly two
      times). The solubility and in vitro drug release rates increased with an increase
      in PVP concentration (from 2.5 to 10%). The SEM studies showed that the crystal
      posseses a good spherical shape with smooth and regular surface.

PMID- 17507315
TI  - Development and in vitro evaluation of buccoadhesive carvedilol tablets.
AB  - Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and
      Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with
      varying concentrations of polymers. Formulations of the BC or BD series were
      composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE
      series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for
      in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro
      drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum
      release of the drug (88.7 +/- 0.4%) with the Higuchi model release profile and
      permeated 21.5 +/- 2.9% of the drug (flux 8.35 +/- 0.291 microg h(-1)cm(-2))
      permeation coefficient 1.34 +/- 0.05 cm h(-1)) through porcine buccal membrane.
      BC3 formulation showed 1.62 +/- 0.15 N of peak detachment force and 0.24 +/- 0.11
      mJ of work of adhesion. FTIR results showed no evidence of interaction between
      the drug and polymers. XRD study revealed that the drug is in crystalline form in
      the polymer matrix. The results indicate that suitable bioadhesive buccal tablets
      with desired permeability could be prepared.

PMID- 17507316
TI  - Topical dosage form of valdecoxib: preparation and pharmacological evaluation.
AB  - Valdecoxib, a selective COX-2 inhibitor, produces serious side effects when given
      orally. This has led to its withdrawal. Topical application of valdecoxib was
      formulated and evaluated for its efficacy and safety. Standard procedures were
      followed and male Wistar albino rats were used to test the anti-inflammatory
      effect and effect in hyperalgesic conditions. Ointments, creams, and gels
      containing valdecoxib 1% (m/m) were prepared. These were tested for physical
      appearance, pH, spreadability, drug content uniformity, in vitro diffusion. Gel
      prepared using Carbopol 940 (F-X) was selected after the analysis of the results.
      Formulation F-X was evaluated for acute skin irritancy, anti-inflammatory effect,
      optimum effective concentration of valdecoxib, effect on hyperalgesia, inhibition
      of the granulation tissue formation and anti-arthritic effect. Determination of
      valdecoxib in test animals plasma and determining the blood clotting time and
      bleeding time were conducted to study the safety of topical valdecoxib.
      Valdecoxib gel containing 1% (m/m) of the drug was significantly (p < 0.05) more
      effective in inhibiting hyperalgesia associated with inflammation, compared to
      placebo gel, but exhibited significantly (p < 0.05) lower suppression of
      inflammation than commercial rofecoxib gel. Concentration of valdecoxib used in
      the preparation minimizes the risk of systemic effects, as shown by the analysis
      of rat plasma for the presence of valdecoxib; hence, this may be the alternative
      to oral preparations. The bleeding and clotting time showed no significant
      difference before and after application of F-X.

PMID- 17507317
TI  - Use of ceric ammonium sulphate and two dyes, methyl orange and indigo carmine, in
      the determination of lansoprazole in pharmaceuticals.
AB  - Two spectrophotometric methods are proposed for the assay of lansoprazole (LPZ)
      in bulk drug and in dosage forms using ceric ammonium sulphate (CAS) and two
      dyes, methyl orange and indigo carmine, as reagents. The methods involve addition
      of a known excess of CAS to LPZ in acid medium, followed by determination of
      residual CAS by reacting with a fixed amount of either methyl orange, measuring
      the absorbance at 520 nm (method A), or indigo carmine, measuring the absorbance
      at 610 nm (method B). In both methods, the amount of CAS reacted corresponds to
      the amount of LPZ and the measured absorbance was found to increase linearly with
      the concentration of LPZ, which is corroborated by the correlation coefficients
      of 0.9979 and 0.9954 for methods A and B, respectively. The systems obey Beer's
      law for 0.5-7.0 microg mL(-1) and 0.25-3.0 microg mL(-1) for methods A and B,
      respectively. The apparent molar absorptivities were calculated to be 3.0 x 10(4)
      and 4.4 x 10(4) L mol(-1) cm(-1) for methods A and B, respectively. The limits of
      detection (LOD) and quantification (LOQ) were calculated to be 0.08 and 0.25
      microg mL(-1) for method A, and 0.09 and 0.27 microg mLs(-1) for method B,
      respectively. The intra-day and inter-day precision and accuracy of the methods
      were evaluated according to the current ICH guidelines. Both methods were of
      comparable accuracy (er < or = 2 %). Also, both methods are equally precise as
      shown by the relative standard deviation values < 1.5%. No interference was
      observed from common pharmaceutical adjuvants. The accuracy of the methods was
      further ascertained by performing recovery studies using the standard addition
      method. The methods were successfully applied to the assay of LPZ in capsule
      preparations and the results were statistically compared with those of the
      literature UV-spectrophotometric method by applying Student's t-test and F-test.

PMID- 17507318
TI  - Spectrophotometric determination of pefloxacin mesylate in pharmaceuticals.
AB  - A spectrophotometric method is described for assay of pefloxacin mesylate (PFM)
      in bulk drug and in tablets. The method is based on back extraction of the
      bromophenol blue dye at pH 5.2 from the dye-drug ion pair followed by measurement
      of the dye absorbance at 590 nm. The working conditions of the method were
      investigated and optimized. Beer's law plot showed a good correlation in the
      concentration range of 0.15-1.25 microg mL(-1). Sensitivity indices such as molar
      absorptivity, limits of detection and quantification are reported. Intra-day and
      inter-day precision, and accuracy of the methods were established according to
      the ICH guidelines, and the er values were in the range of -1.7 to 1.8% with RSD
      values ranging from 1.0 to 1.1%. The method was successfully applied to the assay
      of PFM in tablet preparations with recoveries varying from 97.5 to 101.9%, with
      standard deviation in the range of 0.6 to 1.9. The results were statistically
      compared with those of the reference method by applying Student's t-test and F
      test. Accuracy evaluated by means of the spike recovery method, range from 97.0
      to 106.0%, with precision better than 3%.

PMID- 17507319
TI  - Micellar liquid chromatographic analysis of benzyl alcohol and benzaldehyde in
      injectable formulations.
AB  - An accurate, sensitive and selective reversed-phase micellar liquid
      chromatographic method was developed for simultaneous determination of benzyl
      alcohol and benzaldehyde. This method was applied in different injectable
      formulations containing diclofenac, piroxicam, lincomycin and clindamycin. The
      method showed excellent linearity in the range of 10-100 microg mL(-1) and 1-20
      microg mL(-1) with the limit of detection (S/N = 3) 0.25 microg mL(-1) (2.3 x 10(
      6) mol L(-1)) and 0.12 microg mL(-1) (1.13 x 10(-6) mol L(-1)) for benzyl alcohol
      and benzaldehyde, respectively. The suggested method was successfully applied to
      the analysis of the studied drugs in bulk with average recoveries of 100.1 +/-
      1.0% for benzyl alcohol and 100.4 +/- 1.6% for benzaldehyde, and to the
      determination of benzyl alcohol and benzaldehyde in injectable formulations with
      the respective average recoveries of 99.8 +/- 0.3 and 100.0 +/- 0.4%.

PMID- 17507320
TI  - Hepatoprotective effect of the ethyl acetate extract of Teucrium polium L.
      against carbontetrachloride-induced hepatic injury in rats.
AB  - Hepatoprotective activity of the ethyl acetate extract of Teucrium polium L. was
      investigated using rats with CCl4-induced liver damage. Specific biochemical
      parameters (glutathione peroxidase, superoxide dismutase, reduced glutathione and
      total antioxidative status) were estimated in blood and in liver homogenate.
      Lipid peroxidation in CCl4-intoxicated rats was evidenced by a marked increment
      in the levels of thiobarbituric acid reactive substances. Histopatological
      examinations of the liver were undertaken to monitor the liver status. Silymarin
      was used as a standard to compare the hepatoprotective activity of the extract.
      Some biochemical parameters in groups treated with the Teucrium polium extract at
      a dose of 25 mg kg(-1), showed significantly different values than that of the
      CCl4--treated group. The liver biopsy of all experimental rat groups treated with
      the Teucrium polium ethyl acetate extract showed significant restoration of the
      normal histomorphological pattern of liver cells. The study substantiates the
      potential hepatoprotective activity of the ethyl acetate extract of Teucrium
      polium L.

PMID- 17507321
TI  - Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG
      359.
AB  - PURPOSE: Non-nucleoside reverse transcriptase inhibitor (NNRTI)
      hypersusceptibility (HS) improves virologic response to those agents, but
      phenotypic susceptibility cut-points, and methods to determine the cut-points,
      have not been completely defined. METHOD: Phenotypic drug susceptibility (fold
      change in IC50 [FC]) was determined for 96 randomly selected antiretroviral
      experienced, NNRTI-naive patients who received a delavirdine (DLV)-containing
      regimen in ACTG 359. A weighted FC score was used to account for other regimen
      agents. Regression models were used to define baseline DLV HS cut-points using
      week 4 or week 16 responses. RESULTS: At study entry, DLV HS was present in 36%
      (35/96) of patients. Models explored HS cut-points from 0.2-1.0 using the week 4
      virologic response. Using either a binary or continuous endpoint, DLV HS cut
      points between 0.3 and 0.4 were identified. The classification and regression
      tree (CART) analysis identified baseline DLV FC <0.44 as a predictor of week 4
      response. CONCLUSIONS: In relating drug HS to virologic response, several
      different analytic methods identified a DLV HS FC cut-point of 0.3-0.4. In
      refining phenotypic cut-points, early virologic responses (not confounded by
      rebound) may be better metrics than later responses, especially for drugs with
      low genetic barriers, such as DLV.

PMID- 17507322
TI  - Modelling-based prediction of clinical benefits from etravirine in the TMC125
      C223 trial.
AB  - OBJECTIVE: To predict the decrease in progression to AIDS or death based on the
      treatment benefit of etravirine over active control on CD4 counts and HIV RNA.
      METHOD: In the TMC125-C223 trial, treatment-experienced patients (n = 199,
      baseline median CD4 99 cells/microL, HIV RNA 4.7 log10 copies/mL) received
      optimized background treatment plus either etravirine 400 mg bid, etravirine 800
      mg bid, or control. CD4 and HIV RNA data were used to predict progression to AIDS
      or death with two methods: regression method - data from clinical endpoint trials
      were used to correlate previous CD4 and HIV RNA treatment benefits with clinical
      progression; CD4 categorization method - data from the EuroSIDA cohort were used
      to predict rates of disease progression. RESULTS: At week 48, CD4 counts rose by
      49 cells/microL for etravirine 800 mg bid versus 10 cells/microL for control; HIV
      RNA fell by -1.0 and -0.14 log10 at week 48 in the two groups. The regression
      method predicted a 39% comparative reduction in progression to AIDS/death from
      HIV RNA levels and a 33% reduction in progression from CD4 counts. The
      categorization method predicted a comparative reduction of 39% based on HIV RNA
      levels and a reduction of 31% based on CD4 counts. CONCLUSION: Based on the
      efficacy results from the TMC125-C223 trial, the benefits of etravirine 800 mg
      bid versus control in raising CD4 counts and suppressing HIV RNA are predicted to
      lower progression rates to AIDS/death by 31%-39% for etravirine treatment, using
      two independent methods.

PMID- 17507323
TI  - Ecological study of the predictors of successful management of dyslipidemia in
      HIV-infected patients on ART: the Swiss HIV Cohort Study.
AB  - PURPOSE: Antiretroviral therapy (ART) may induce metabolic changes and increase
      the risk of coronary heart disease (CHD). Based on a health care system approach,
      we investigated predictors for normalization of dyslipidemia in HIV-infected
      individuals receiving ART. METHOD: Individuals included in the study were
      registered in the Swiss HIV Cohort Study (SHCS), had dyslipidemia but were not on
      lipid-lowering medication, were on potent ART for >or= 3 months, and had >or= 2
      follow-up visits. Dyslipidemia was defined as two consecutive total cholesterol
      (TC) values above recommended levels. Predictors of achieving treatment goals for
      TC were assessed using Cox models. RESULTS: Analysis included 958 individuals
      with median followup of 2.3 years (IQR 1.2-4.0). 454 patients (47.4%) achieved TC
      treatment goals. In adjusted analyses, variables significantly associated with a
      lower hazard of reaching TC treatment goals were as follows: older age (compared
      to 18-37 year olds: hazard ratio [HR] 0.62 for 45-52 year olds, 95% CI 0.47-0.82;
      HR 0.40 for 53-85, 95% CI 0.29-0.54), diabetes (HR 0.39, 95% CI 0.26-0.59),
      history of coronary heart disease (HR 0.27, 95% CI 0.10-0.71), higher baseline TC
      (HR 0.78, 95% CI 0.71-0.85), baseline triple nucleoside regimen (HR 0.12 compared
      to PI-only regimen, 95% CI 0.07-0.21), longer time on PI-only regimen (HR 0.39,
      95% CI 0.33-0.46), longer time on NNRTI only regimen (HR 0.35, 95% CI 0.29-0.43),
      and longer time on PI/NNRTI regimen (HR 0.34, 95% CI 0.26-0.43). Switching ART
      regimen when viral load was undetectable was associated with a higher hazard of
      reaching TC treatment goals (HR 1.48, 95% CI 1.14-1.91). CONCLUSION: In SHCS
      participants on ART, several ART-related and not ART-related epidemiological
      factors were associated with insufficient control of dyslipidemia. Control of
      dyslipidemia in ART recipients must be further improved.

PMID- 17507325
TI  - Outbreak of syphilis, but not of acute hepatitis C, among HIV-infected homosexual
      men in Madrid.
AB  - BACKGROUND: Clustered cases of acute hepatitis C virus (HCV) infection,
      frequently accompanied by sexually transmitted diseases, have recently been
      reported among men who have sex with men (MSM) in several European cities.
      METHOD: We performed a retrospective record of cases of syphilis in a large
      cohort of HIV-infected individuals on regular follow-up in Madrid, Spain. HCV
      testing was carried out in all of them. RESULTS: A total of 53 diagnosis of
      syphilis were made during the previous 4 years (2002 to 2005) in 729 HIV-infected
      MSM on regular follow-up. However, in only 2 of them (3.7%) asymptomatic HCV
      seroconversion occurred at the time of the syphilis episode. Both patients
      developed chronic hepatitis C. CONCLUSION: Acute HCV infection should
      periodically be ruled out in all HIV-infected MSM engaged in sexual risky
      behaviors presenting with syphilis.

PMID- 17507324
TI  - Safety and efficacy of posaconazole in the long-term treatment of azole
      refractory oropharyngeal and esophageal candidiasis in patients with HIV
      infection.
AB  - PURPOSE: To evaluate safety and efficacy of long-term posaconazole in HIV
      infected patients with azole-refractory oropharyngeal candidiasis and/or
      esophageal candidiasis. METHOD: In this noncomparative, open-label study,
      participants received oral posaconazole 400 mg twice daily (bid) for 3 months.
      Enrolled patients (N = 100) included 60 from a previous 1-month acute study of
      posaconazole and 40 posaconazole-naive participants. Participants with a clinical
      response could be followed untreated for up to 1 month afterwards. Participants
      who relapsed during follow-up, showed improvement at the end of 3 months of
      treatment (EOT), or were cured but likely to benefit from further therapy could
      continue on posaconazole 400 mg bid for up to 12 months. RESULTS: In the modified
      intent-to-treat population, clinical response (cure or improvement) occurred in
      85.6% (77/90) at EOT. The results were similar in the previously treated
      participants and the posaconazole-naive participants, 88.1% (52/59) and 80.6%
      (25/31), respectively. Posaconazole was well-tolerated, showing a similar safety
      profile during the 3-month study period and during suppressive therapy. The most
      frequently reported treatment-related adverse event was vomiting (4/100, 4%)
      during the early follow-up period (on or before day 105) and elevated hepatic
      enzymes (3/51, 6%) during the long-term follow-up (after day 105). CONCLUSION:
      Oral posaconazole 400 mg bid demonstrated long-term safety, tolerability, and
      efficacy, offering a long-term, suppressive treatment option for HIV-infected
      participants with azole-refractory mucosal candidiasis.

PMID- 17507326
TI  - Long-term control of viral residual replication under maintenance therapy with
      Trizivir after a quadruple induction regimen in HIV-1-infected adults (Suburbs
      trial).

PMID- 17507327
TI  - Emergence of protease resistance during simplification therapy with
      lopinavir/ritonavir alone.

PMID- 17507329
TI  - The mechanical power requirements of avian flight.
AB  - A major goal of flight research has been to establish the relationship between
      the mechanical power requirements of flight and flight speed. This relationship
      is central to our understanding of the ecology and evolution of bird flight
      behaviour. Current approaches to determining flight power have relied on a
      variety of indirect measurements and led to a controversy over the shape of the
      power-speed relationship and a lack of quantitative agreement between the
      different techniques. We have used a new approach to determine flight power at a
      range of speeds based on the performance of the pectoralis muscles. As such, our
      measurements provide a unique dataset for comparison with other methods. Here we
      show that in budgerigars (Melopsittacus undulatus) and zebra finches (Taenopygia
      guttata) power is modulated with flight speed, resulting in U-shaped power-speed
      relationship. Our measured muscle powers agreed well with a range of powers
      predicted using an aerodynamic model. Assessing the accuracy of mechanical power
      calculated using such models is essential as they are the basis for determining
      flight efficiency when compared to measurements of flight metabolic rate and for
      predicting minimum power and maximum range speeds, key determinants of optimal
      flight behaviour in the field.

PMID- 17507330
TI  - Temporal order and the evolution of complex acoustic signals.
AB  - The evolution of complex signals may be favoured by hidden preferences or pre
      existing sensory biases. Females of two species of grey treefrogs (Hyla
      chrysoscelis and Hyla versicolor) were tested with combinations of a conspecific
      advertisement call and acoustic appendages. Appendages consisted of aggressive
      calls and segments of advertisement calls from conspecific males and males of
      three other species and bursts of filtered noise. When a wide variety of these
      acoustic appendages followed the advertisement call, the resulting compound
      signal was often more attractive than the same advertisement call alone. When the
      same appendages led advertisement calls, however, the compound signal was never
      more attractive and sometimes less attractive. The order effect was especially
      strong in tests of H. versicolor in which advertisement-call duration was
      decreased. These results cannot be explained by a general pre-existing bias for
      extra stimulation per se. Rather, order and other effects may constrain the
      evolution and subsequent modification of complex and extravagant signals,
      examples of which have been reported for a wide range of taxa.

PMID- 17507331
TI  - Emergence of drug resistance: implications for antiviral control of pandemic
      influenza.
AB  - Given the danger of an unprecedented spread of the highly pathogenic avian
      influenza strain H5N1 in humans, and great challenges to the development of an
      effective influenza vaccine, antiviral drugs will probably play a pivotal role in
      combating a novel pandemic strain. A critical limitation to the use of these
      drugs is the evolution of highly transmissible drug-resistant viral mutants.
      Here, we develop a mathematical model to evaluate the potential impact of an
      antiviral treatment strategy on the emergence of drug resistance and containment
      of a pandemic. The results show that elimination of the wild-type strain depends
      crucially on both the early onset of treatment in indexed cases and population
      level treatment. Given the probable delay of 0.5-1 day in seeking healthcare and
      therefore initiating therapy, the findings indicate that a single strategy of
      antiviral treatment will be unsuccessful at controlling the spread of disease if
      the reproduction number of the wild-type strain (R0s) exceeds 1.4. We demonstrate
      the possible occurrence of a self-sustaining epidemic of resistant strain, in
      terms of its transmission fitness relative to the wild-type, and the reproduction
      number R0s. Considering reproduction numbers estimated for the past three
      pandemics, the findings suggest that an uncontrollable pandemic is likely to
      occur if resistant viruses with relative transmission fitness above 0.4 emerge.
      While an antiviral strategy is crucial for containing a pandemic, its
      effectiveness depends critically on timely and strategic use of drugs.

PMID- 17507333
TI  - The cover. Portrait of Pablo Picasso.

PMID- 17507332
TI  - Complex interactions with females and rival males limit the evolution of sperm
      offence and defence.
AB  - Postcopulatory sexual selection favours males which are strong offensive and
      defensive sperm competitors. As a means of identifying component traits
      comprising each strategy, we used an experimental evolution approach. Separate
      populations of Drosophila melanogaster were selected for enhanced sperm offence
      and defence. Despite using a large outbred population and evidence of substantive
      genetic variation for each strategy, neither trait responded to selection in the
      two replicates of this experiment. Recent work with fixed chromosome lines of D.
      melanogaster suggests that complex genotypic interactions between females and
      competing males contribute to the maintenance of this variation. To determine
      whether such interactions could explain our lack of response to selection on
      sperm offence and defence, we quantified sperm precedence across multiple sperm
      competition bouts using an outbred D. melanogaster population exhibiting
      continuous genetic variation. Both offensive and defensive sperm competitive
      abilities were found to be significantly repeatable only across matings involving
      ejaculates of the same pair of males competing within the same female. These
      repeatabilities decreased when the rival male stayed the same but the female
      changed, and they disappeared when both the rival male and the female changed.
      Our results are discussed with a focus on the complex nature of sperm precedence
      and the maintenance of genetic variation in ejaculate characteristics.

PMID- 17507334
TI  - Common gene variant linked to obesity.

PMID- 17507335
TI  - New drug-eluting stents under study.

PMID- 17507336
TI  - Study examines effects of advance access to emergency contraception.

PMID- 17507337
TI  - Ethanol-fueled vehicles could pose health risk.

PMID- 17507338
TI  - Iron reduction and cardiovascular outcomes.

PMID- 17507339
TI  - Iron reduction and cardiovascular outcomes.

PMID- 17507340
TI  - Low- vs high-dose estradiol vaginal ring in treatment of sexual difficulties.

PMID- 17507341
TI  - Analytic approaches to observational studies with treatment selection bias.

PMID- 17507342
TI  - Analytic approaches to observational studies with treatment selection bias.

PMID- 17507343
TI  - Using observational data to estimate treatment effects.

PMID- 17507344
TI  - Effects of different doses of physical activity on cardiorespiratory fitness
      among sedentary, overweight or obese postmenopausal women with elevated blood
      pressure: a randomized controlled trial.
AB  - CONTEXT: Low levels of cardiorespiratory fitness are associated with high risk of
      mortality, and improvements in fitness are associated with reduced mortality
      risk. However, a poor understanding of the physical activity-fitness dose
      response relation remains. OBJECTIVE: To examine the effect of 50%, 100%, and
      150% of the NIH Consensus Development Panel recommended physical activity dose on
      fitness in women. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial
      of 464 sedentary, postmenopausal overweight or obese women whose body mass index
      ranged from 25.0 to 43.0 and whose systolic blood pressure ranged from 120.0 to
      159.9 mm Hg. Enrollment took place between April 2001 and June 2005 in the
      Dallas, Tex, area. INTERVENTION: Participants were randomly assigned to 1 of 4
      groups: 102 to the nonexercise control group and 155 to the 4-kcal/kg, 104 to the
      8-kcal/kg, and 103 to the 12-kcal/kg per week energy-expenditure groups for the 6
      month intervention period. Target training intensity was the heart rate
      associated with 50% of each woman's peak Vo2. MAIN OUTCOME MEASURE: The primary
      outcome was aerobic fitness assessed on a cycle ergometer and quantified as peak
      absolute oxygen consumption (Vo2abs, L/min). RESULTS: The mean (SD) baseline
      Vo2abs values were 1.30 (0.25) L/min. The mean (SD) minutes of exercising per
      week were 72.2 (12.3) for the 4-kcal/kg, 135.8 (19.5) for the 8-kcal/kg, and
      191.7 (33.7) for the 12-kcal/kg per week exercise groups. After adjustment for
      age, race/ethnicity, weight, and peak heart rate, the exercise groups increased
      their Vo2abs compared with the control group by 4.2% in the 4-kcal/kg, 6.0% in
      the 8-kcal/kg, and 8.2% in the 12-kcal/kg per week groups (P<.001 for each vs
      control; P for trend <.001). There was no treatment x subgroup interaction for
      age, body mass index, weight, baseline Vo2abs, race/ethnicity, or baseline
      hormone therapy use. There were no significant changes in systolic or diastolic
      blood pressure values from baseline to 6 months in any of the exercise groups vs
      the control group. CONCLUSION: In this study, previously sedentary, overweight or
      obese postmenopausal women experienced a graded dose-response change in fitness
      across levels of exercise training. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00011193.

PMID- 17507345
TI  - Effects of a low-glycemic load vs low-fat diet in obese young adults: a
      randomized trial.
AB  - CONTEXT: The results of clinical trials involving diet in the treatment of
      obesity have been inconsistent, possibly due to inherent physiological
      differences among study participants. OBJECTIVE: To determine whether insulin
      secretion affects weight loss with 2 popular diets. DESIGN, SETTING, AND
      PARTICIPANTS: Randomized trial of obese young adults (aged 18-35 years; n = 73)
      conducted from September 2004 to December 2006 in Boston, Mass, and consisting of
      a 6-month intensive intervention period and a 12-month follow-up period. Serum
      insulin concentration at 30 minutes after a 75-g dose of oral glucose was
      determined at baseline as a measure of insulin secretion. Outcomes were assessed
      at 6, 12, and 18 months. Missing data were imputed conservatively. INTERVENTIONS:
      A low-glycemic load (40% carbohydrate and 35% fat) vs low-fat (55% carbohydrate
      and 20% fat) diet. MAIN OUTCOME MEASURES: Body weight, body fat percentage
      determined by dual-energy x-ray absorptiometry, and cardiovascular disease risk
      factors. RESULTS: Change in body weight and body fat percentage did not differ
      between the diet groups overall. However, insulin concentration at 30 minutes
      after a dose of oral glucose was an effect modifier (group x time x insulin
      concentration at 30 minutes: P = .02 for body weight and P = .01 for body fat
      percentage). For those with insulin concentration at 30 minutes above the median
      (57.5 microIU/mL; n = 28), the low-glycemic load diet produced a greater decrease
      in weight (-5.8 vs -1.2 kg; P = .004) and body fat percentage (-2.6% vs -0.9%; P
      = .03) than the low-fat diet at 18 months. There were no significant differences
      in these end points between diet groups for those with insulin concentration at
      30 minutes below the median level (n = 28). Insulin concentration at 30 minutes
      after a dose of oral glucose was not a significant effect modifier for
      cardiovascular disease risk factors. In the full cohort, plasma high-density
      lipoprotein cholesterol and triglyceride concentrations improved more on the low
      glycemic load diet, whereas low-density lipoprotein cholesterol concentration
      improved more on the low-fat diet. CONCLUSIONS: Variability in dietary weight
      loss trials may be partially attributable to differences in hormonal response.
      Reducing glycemic load may be especially important to achieve weight loss among
      individuals with high insulin secretion. Regardless of insulin secretion, a low
      glycemic load diet has beneficial effects on high-density lipoprotein cholesterol
      and triglyceride concentrations but not on low-density lipoprotein cholesterol
      concentration. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00130299.

PMID- 17507346
TI  - Genomic instability within tumor stroma and clinicopathological characteristics
      of sporadic primary invasive breast carcinoma.
AB  - CONTEXT: That genomic alterations occur in both the epithelium and stroma of
      sporadic breast cancers has been documented by several groups. However, whether
      these microenvironmental alterations relate to clinicopathological features is
      unknown. OBJECTIVE: To analyze the relationship between stromal genomic
      alterations and presenting clinicopathological features in sporadic breast
      cancer. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cross-sectional
      analysis of DNA from the epithelium and stroma of 220 primary sporadic invasive
      breast carcinomas for global genomic alterations manifested by loss of
      heterozygosity/allelic imbalance with 386 microsatellite markers. Data were
      collected from October 2003 through June 2006 from samples at Brigham and Women's
      Hospital, Boston, Mass. MAIN OUTCOME MEASURES: Association of the loss of
      heterozygosity/allelic imbalance, in both the stroma and epithelium, with
      presenting clinicopathological features, such as tumor grade, expression status
      of estrogen receptor and progesterone receptor, human epidermal growth factor
      receptor 2, clinical stage, and regional lymph node metastasis status.
      Associations were assessed in regression models and tested with Fisher exact
      test. Bonferroni correction was applied to P values, with significance set at
      P<.0022. RESULTS: We found significant associations between loss of
      heterozygosity/allelic imbalance on chromosome 11 in the stroma and tumor grade
      (P = .0013), on chromosomes 1, 2, 5, 18, 20, and 22 in the stroma and regional
      lymph node metastasis (P = .0002-.0016), and on chromosome 14 in the epithelium
      and progesterone-receptor expression status (P = .002). Specific markers
      contributing to the loss of heterozygosity/allelic imbalance on chromosome 11 in
      the stroma associated with tumor grade were D11S1999 (P = .00055) and D11S1986 (P
      = .042). The loss of heterozygosity/allelic imbalance at various markers in the
      stroma was significantly associated with regional lymph node metastasis: ATA42G12
      (chromosome 1, P = .00095), D5S1457 (P = .00095), D5S1501 (P = .0011), D5S816 (P
      = .0008), D18S858 (P = .0026), D20S103 (P = .0027), D20S851 (P = .0045), D22S683
      (P = .00033), and D22S1045 (P = .0013). CONCLUSIONS: There were more correlations
      between clinicopathological features and the loss of heterozygosity/allelic
      imbalance in the stroma than in the epithelium, suggesting that stromal genomic
      alterations may help account for clinical diversity. Future research is necessary
      to validate these results and investigate their significance for prognosis and
      outcome.

PMID- 17507348
TI  - A 68-year-old man with COPD contemplating colon cancer surgery.
AB  - Mr A is a 68-year-old man with a history of melena who was found to have a mass
      in his colon that was suspicious for possible malignancy. His 75-pack-year
      smoking history has resulted in a chronic daily cough and the diagnosis of
      chronic obstructive pulmonary disease. On physical examination, he has wheezes,
      decreased breath sounds, and a prolonged expiratory phase; his forced expiratory
      volume in the first second (FEV1) is 1.34 L (47% predicted). Mr A needs surgery
      for potentially curative treatment for presumed colon cancer, but he is
      understandably worried about the effect of his lung disease on his surgical risk.
      In particular, he is worried that he may not be able to be weaned off the
      ventilator after surgery. This discussion reviews the important patient- and
      procedure-related risk factors for pulmonary complications after surgery, the
      role of preoperative testing, and the evidence supporting strategies to reduce
      the risk of pulmonary complications as they apply to Mr A.

PMID- 17507347
TI  - Issues in the registration of clinical trials.
AB  - Public concerns about the perils associated with incomplete or delayed reporting
      of results from clinical trials has heightened interest in trial registries and
      results databases. Here we review the current status of trial registration
      efforts and the challenges in developing a comprehensive system of trial
      registration and reporting of results. ClinicalTrials.gov, the largest trial
      registry with 36 249 trials from approximately 140 countries, has procedures in
      place to help ensure that records are valid and informative. Key challenges
      include the need to minimize inadvertent duplicate registrations, to ensure that
      interventions have unambiguous names, and to have a search engine that identifies
      all trials that meet a user's specifications. Recent policy initiatives have
      called for the development of a database of trial results. Several issues
      confound the implementation of such a database, including the lack of an accepted
      format or process for providing summaries of trial results to the public and
      concerns about disseminating data in the absence of independent scientific
      review.

PMID- 17507349
TI  - What cannot be said on television about health care.

PMID- 17507350
TI  - Academic mentoring--how to give it and how to get it.

PMID- 17507351
TI  - Dose-response relation between physical activity and fitness: even a little is
      good; more is better.

PMID- 17507353
TI  - JAMA patient page. Preparing for surgery: evaluation of lung function.

PMID- 17507354
TI  - Prevalence and prognostic impact of comorbidities in heart failure patients with
      implantable cardioverter defibrillator.
AB  - AIMS: This study assessed the prevalence and the prognostic impact of
      comorbidities in heart failure patients with implantatable cardioverter
      defibrillator (ICD). METHODS AND RESULTS: We prospectively enrolled 146 patients
      with chronic heart failure, an ICD, and systolic dysfunction (mean ejection
      fraction 29 +/- 10%). Cardiac death was chosen as the primary endpoint. Death or
      appropriate ICD therapy, i.e. antitachycardia pacing/shock due to sustained
      ventricular tachycardia or ventricular fibrillation, was chosen as the secondary
      endpoint. Seventy-five patients (52%) had chronic kidney disease (defined as an
      estimated glomerular filtration rate <60 mL/min/1.73 m(2)), 39 patients (27%)
      were anaemic, and 34 patients (23%) had diabetes mellitus. During a follow-up of
      663 +/- 400 days, 22 patients (15%) died, and 41 patients (28%) received an
      appropriate ICD therapy. By multivariate Cox analysis, independent predictors of
      cardiac death were chronic kidney disease, age, and NYHA functional class.
      Death/appropriate ICD therapy were independently predicted by chronic kidney
      disease and QRS duration. In the presence of chronic kidney disease, outcome was
      significantly worse when compared with the absence (event-free survival rate 51
      vs. 76%, P < 0.001). CONCLUSION: In heart failure patients with an ICD,
      comorbidities are frequent but only the presence of chronic kidney disease is
      independently associated with increased morbidity and mortality.

PMID- 17507355
TI  - Ventricular rate smoothing for atrial fibrillation: a quantitative comparison
      study.
AB  - AIMS: To quantitatively compare the ventricular rate-smoothing (VRS) effects of
      different ventricular pacing (VP) protocols for atrial fibrillation (AF). METHODS
      AND RESULTS: Using a recently developed open-source model that can simulate the
      ventricular response in AF and VP, the performance of fixed-rate pacing and four
      previously published VRS algorithms were assessed by the mean RR (mRR), the root
      mean square of successive RR differences (RMSSD), the percentage of ventricular
      senses (VS%), and the percentage of short RR intervals (sRR%). All pacing
      protocols cause rate-dependent reduction of RMSSD, VS%, and sRR% with or without
      shortening of mRR compared to spontaneous AF. Fixed-rate pacing was more
      sensitive to the intrinsic rate than the VRS algorithms. The performance was
      generally comparable between different VRS algorithms, although higher mRR and
      VS% can be achieved at the expense of larger RMSSD and sRR%. CONCLUSION: The
      effect of VP on ventricular rhythm in AF depends on both intrinsic rate and the
      aggressiveness of the pacing protocol. Adequate rate control is necessary for
      effective operation of the VRS algorithm. Choosing VRS algorithm should balance
      between the beneficial effects of rate regularization and the negative effects of
      increasing heart rate and percentage of VP.

PMID- 17507356
TI  - Single-centre experience with coronary sinus lead stability and long-term pacing
      parameters.
AB  - AIMS: To compare both short- and long-term stability and pacing parameters of CS
      leads. Long-term maintenance of coronary sinus (CS) pacing lead position has not
      yet been assessed by serial X-ray digital imaging. METHODS AND RESULTS: Using X
      ray digital imaging in anteroposterior and left lateral views, we performed
      analysis of the CS lead position at the end of the implantation procedure, 48 h
      following implantation and after 12 months in 93 consecutive patients. Attain OTW
      leads, QuickSite leads and EasyTrak leads were implanted in 44, 12 and 37 cases,
      respectively. X-ray detectable late CS lead dislodgement was observed in 8 cases
      (8.6%) during 12-months follow-up. Dislodgment was once accompanied by loss of
      capture and need for repositioning. Another two major dislodgements occurred
      without any threshold change. Five (5.4%) minor dislocations occurred with either
      a decrease or an increase in pacing threshold. Left ventricular (LV) pacing
      threshold was changed by >or= 1 V after 12 months in 14 patients (15%) when
      compared to values 48 h after implantation. All but one case of >or= 1 V
      threshold change (either positive or negative) occurred without any radiological
      evidence of lead displacement. LV pacing threshold was significantly higher than
      RV pacing threshold at both baseline and during follow-up. Leads from all three
      manufacturers had comparable pacing thresholds 12 months following implantation.
      CONCLUSION: The position of CS leads may change during 1-year follow-up. However,
      it rarely required reoperation in the selected group of patients. Long-term
      pacing parameters between different manufacturers are comparable. Increase in
      pacing threshold is not a reliable marker of CS lead dislodgement.

PMID- 17507357
TI  - Catheter ablation of premature ventricular contractions originating from the His
      bundle region.
AB  - We describe a 35-year-old man with idiopathic frequent premature ventricular
      contractions (PVCs) originating from the His-bundle region, where a low frequency
      ventricular potential was recorded in the bipolar recording and QR pattern in the
      unipolar recording. Electro-anatomical mapping revealed a confined low voltage
      zone (<1.2 mV) in the His-bundle region, and the activation spread out radially
      to the entire right ventricle. The PVCs were successfully abolished without any
      atrioventricular block by a step-wise incremental radiofrequency energy
      application to the His-bundle region. The patient has remained free from PVCs or
      any symptoms without medication during a 23 month follow-up period.

PMID- 17507358
TI  - Defibrillation testing at the time of implantation of cardioverter defibrillator
      in the clinical practice: a nation-wide survey.
AB  - AIMS: Despite an effective defibrillation testing (DT) is considered mandatory to
      be consistent with the rules of good clinical practice, some physicians are
      concerned about the risk of complications related to the induction test, and in
      real world clinical practice, several implant procedures are performed without
      any induction test. We conducted a systematic nation-wide retrospective survey in
      order to determine the DT rate and its complications. METHODS AND RESULTS: An ad
      hoc questionnaire was sent to all 343 Italian implanting centres and the data
      from the 229 (67%) centres that answered were analysed. During the year 2005, a
      total of 7857 patients underwent a first implantation of cardioverter
      defibrillator (ICD), 38% of which with cardiac resynchronization therapy (CRT).
      Of these, 2356 (30%) were implanted without any induction test. In 35 (15%)
      centres, the induction test was performed in < 25% of the patients, whereas in
      136 (59%) centres, it was performed in > 75% of the patients. At multivariable
      analysis, performed in a subset of 1206 patients from 107 centres, CRT device (OR
      = 1.82) and primary prevention (OR = 1.47) were independent predictors of the
      decision to not perform DT. However, altogether, the clinical variables accounted
      only for 35% of the total variance, whereas the remaining 65% was probably
      unrelated to clinical factors. There was a total of 22 (0.4%) life-threatening
      complications as a consequence of the induction test: 4 deaths (0.07%), 8
      cardiopulmonary arrests requiring resuscitation manoeuvres (0.15%), 6 cardiogenic
      shocks (0.11%), 3 strokes (0.05%), and 1 pulmonary embolism (0.02%). CONCLUSION:
      In real world practice, DT is not performed in a substantial number of patients,
      most of these in the absence of legitimate reasons. The clinical impact of DT vs.
      no DT remains unclear until the not negligible complication rate is compared
      against the long-term potential benefit.

PMID- 17507359
TI  - Coronary sinus spasm during left ventricular lead implantation for biventricular
      pacing.
AB  - The authors present a case of coronary sinus spasm during left ventricular lead
      implantation for biventricular pacing relieved by direct infusion of
      nitroglycerin.

PMID- 17507360
TI  - Effects of complete heart block on myocardial function, morphology, and energy
      metabolism in the rat.
AB  - AIMS: Severe sustained bradycardia may cause acute and possibly chronic
      congestive heart failure (CHF). The aim of this study was to investigate acute
      and chronic effects of complete heart block (CHB) on cardiac function,
      morphology, and creatine (Cr) metabolism. METHODS AND RESULTS: CHB was induced in
      male Sprague-Dawley rats (approximately 250 g, n = 11) by means of electrocautery
      applied to the region of AV node and were compared with controls (n = 15). The
      rats were investigated at 1, 3, and 12 weeks after CHB induction with
      transthoracic echocardiography. Invasive haemodynamic assessment of left and
      right ventricular pressures was performed at 12 weeks. After the sacrifice, the
      hearts were freeze-clamped for analysis of myocardial Cr, and high energy
      phosphometabolites. The efficacy of operative procedure was 54%. The peri
      operative mortality rate was 20%. Heart rate (HR) decreased by approximately 50%
      (P < 0.01) while stroke volume (SV) increased 2.5 times (P < 0.01) in the CHB
      rats. Cardiac index remained unchanged. The rats with CHB grew normally and were
      in no apparent distress. Filling pressures in left and right ventricles were
      normal. The CHB rats developed marked cardiomegaly with biventricular dilatation
      and eccentric left ventricular hypertrophy (P < 0.01). There was no change in the
      myocardial content of Cr and high energy phosphometabolites. CONCLUSION: Rats
      with CHB are compensating for reduction in HR with increased SV without
      haemodynamic and biochemical characteristics of CHF. This model may be useful to
      study the effects of CHB and bradycardia on myocardial structure, function,
      electrophysiology, and metabolism as well as for studies of cell therapy for
      reparation of AV conductance.

PMID- 17507361
TI  - Prediction of atrial fibrillation in patients with cardiac dysfunctions: P wave
      signal-averaged ECG and chemoreflexsensitivity in atrial fibrillation.
AB  - AIMS: Atrial fibrillation (AF) is a common arrhythmia in advanced heart failure.
      The occurrence of AF increases the risk of death and hospitalization for patients
      with heart failure. The results of different studies indicated that patients with
      paroxysmal AF have a longer filtered P wave duration (FPD), a lower root mean
      square voltage of the last 20 ms of the P wave (RMS 20), and a lower
      chemoreflexsensitivity (CHRS). Our study bases on these observations in order to
      examine the methods for predicting AF in patients with a left ventricular
      ejection fraction below 40% without a prior documentation of AF. METHODS AND
      RESULTS: The ratio between the difference of RR intervals in ECG and venous pO(2)
      before and after 5-min oxygen inhalation was measured (ms/mmHg) in order to
      determine the CHRS. A P wave signal-averaged ECG was performed for the
      measurement of FPD and RMS 20. The measurements were only performed in 94
      patients with sinus rhythm. AF occurred during the mean follow-up of 39.9 months
      in 24 patients (26%). There were no significant differences concerning age, heart
      diseases, sex, ejection fraction, heart rate, or the use of drugs. The FPD (130.3
      +/- 4.2 vs. 118.9 +/- 12.4 ms, P < 0.0001) was significantly longer and the RMS
      20 (3.03 +/- 0.95 vs. 3.83 +/- 1.58 microV, P = 0.02) was significantly lower in
      patients with AF than in sinus rhythm. The CHRS did not differ significantly
      between both groups (3.57 +/- 1.49 vs. 3.48 +/- 1.62 ms/mmHg, P = 0.81). The
      chi(2) test showed that the threshold of FPD>or=125 ms and RMS 20 <or=3.3 microV
      revealed the best predictive value for AF. A stepwise logistic regression
      analysis of all variables identified the threshold of FPD>or=125 ms and RMS 20
      <or=3.3 microV (OR 18.71; 95% CI, 4.85-72.16, P < 0.0001) as independent
      predictors for AF. CONCLUSIONS: In summary, our data show that the results of a P
      wave signal-averaged ECG can predict the risk for new onset of AF in patients
      with heart failure. The value of signal-averaged FPD is probably the result of
      reflecting the intra-atrial conduction delay, which is a pathophysiological
      condition for AF. The CHRS is not a suitable method for predicting AF.

PMID- 17507362
TI  - Atrial septal aneurysm mimicking ECG signs of enlarged right atrium.
AB  - In a routine ECG from a young asymptomatic woman, changes in P-wave morphology
      and the frontal plane atrial vector were noted. Two-dimensional echocardiography
      revealed a large atrial septal aneurysm as probable underlying cause. This case
      report demonstrates that non-specific right atrial ECG signs may be indicative of
      lone atrial septal aneurysm.

PMID- 17507363
TI  - Single-step transvenous extraction of a passive fixation lead with delayed
      perforation of the right ventricle.
AB  - Delayed pacemaker lead perforation is a very rare complication and most of the
      published reports involve active fixation leads. The authors report an uneventful
      transvenous extraction of a passive fixation lead, which had a delayed
      perforation of the right ventricle, disclosed two months after pacemaker
      implantation.

PMID- 17507364
TI  - Cardioinhibitory carotid sinus hypersensitivity predicts an asystolic mechanism
      of spontaneous neurally mediated syncope.
AB  - AIMS: We correlated the finding of cardioinhibitory carotid sinus
      hypersensitivity (CSH) with that observed during a spontaneous syncopal relapse
      by means of an implantable loop recorder (ILR). METHODS AND RESULTS: We included
      18 consecutive patients with suspected recurrent neurally mediated syncope and
      positive cardioinhibitory response during carotid sinus massage (max pause 5.5 +/
      1.6 s) who had subsequent documentation of a spontaneous syncope by means of an
      ILR. They were compared with a 2:1 age- and sex-matched group of 36 patients with
      a clinical diagnosis of recurrent neurally mediated syncope and negative response
      to carotid sinus massage, tilt testing and ATP test. Asystole >3 s was observed
      at the time of the spontaneous syncope in 16 (89%) of CSH patients and in 18
      (50%) of the control group (P = 0.007). Sinus arrest was the most frequent
      finding among CSH patients but not among controls (72 vs. 28%, P = 0.003). After
      ILR documentation, 14 CSH patients with asystole received dual-chamber pacemaker
      implantation; during 35 +/- 22 months of follow-up, 2 syncopal episodes recurred
      in 2 patients (14%), and pre-syncope occurred in another 2 patients (14%).
      Syncope burden decreased from 1.68 (95% confidence interval 1.66 - 1.70) episodes
      per patient per year before to 0.04 (0.038-0.042) after pacemaker implant (98%
      relative risk reduction). CONCLUSIONS: In patients with suspected neurally
      mediated syncope, the finding of cardioinhibitory CSH predicts an asystolic
      mechanism at the time of spontaneous syncope and, consequently, suggests a
      possible benefit of cardiac pacing therapy.

PMID- 17507365
TI  - Atrial premature complexes and heart rate have prognostic significance in 1-month
      atrial fibrillation recurrence after electrical cardioversion.
AB  - AIMS: The aim of this study was to investigate the significance of simple 24-h
      Holter (24H) data after electrical cardioversion (CV) for atrial fibrillation
      (AF) recurrence. METHODS: We prospectively studied 47 consecutive patients
      subjected to CV, who successfully converted to sinus rhythm. All underwent
      echocardiography and 24H after CV. AF recurrence was studied at 14 days and 1
      month by second 24H or by interim report of AF. RESULTS: About 53.2% remained in
      sinus rhythm (group I) and the rest recurred to AF (group II). Group I had fewer
      atrial premature complexes per hour (APC/h) (P = 0.002) and lower maximum (max
      HR), average, and minimum heart rates compared with group II (all Ps < 0.05). The
      optimal value of APC/h and max HR with best sensitivity and specificity was 32
      APC/h and 90 bpm, respectively. These findings were the predictors of AF
      recurrence [hazard ratio (HR) = 4.5 with 95% CI = 1.7-11.7 and HR = 4.3 with 95%
      CI = 1.7-10.9, respectively]. Patients with the combination of both predictors
      had greater HR of AF recurrence compared with those with < 32 APC/h and max HR <
      90 bpm (HR = 8.8 with 95% CI = 2.5-31.4). CONCLUSION: Patients with frequent
      APC/h and high max HR are at high risk for 1-month AF recurrence after electrical
      CV.

PMID- 17507366
TI  - Total and high molecular weight adiponectin, haemodynamics, and mortality in
      patients with chronic heart failure.
AB  - AIMS: To evaluate whether plasma high molecular weight (HMW) adiponectin provides
      prognostic information in addition to that obtained from clinical, haemodynamic,
      and biochemical variables previously known to be associated with a high mortality
      in chronic heart failure (CHF) patients. METHODS AND RESULTS: We measured the
      plasma levels of total and HMW adiponectin, atrial natriuretic peptide, brain
      natriuretic peptide (BNP), and N-terminal-proBNP (NT-proBNP), and haemodynamic
      parameters in 449 consecutive CHF patients. Based on body mass index (BMI),
      patients were classified into three groups: low (<21 kg/m(2), n = 133), normal
      (21-25 kg/m(2), n = 205), and high (>25 kg/m(2), n = 111). After adjustment for
      clinical variables associated with CHF including haemodynamics, plasma total
      adiponectin level was an independent prognostic predictor but HMW adiponectin was
      not in the overall patient group. On subgroup analyses, in patients with abnormal
      BMI, plasma total adiponectin level was not an independent prognostic predictor,
      but in patients with normal BMI, plasma levels of log NT-proBNP (P = 0.017) and
      log total adiponectin (P = 0.003) were independent prognostic predictors.
      CONCLUSION: These findings indicate that total adiponectin is more useful for
      assessing mortality risk than HMW adiponectin and a high plasma total adiponectin
      is an independent prognostic predictor especially in CHF patients with normal
      BMI.

PMID- 17507367
TI  - Increased expression of profibrotic neutral endopeptidase and bradykinin type 1
      receptors in stenotic aortic valves.
AB  - AIMS: In aortic stenosis (AS), adverse remodelling of the valves may depend on
      altered local regulation of pro- and antifibrotic systems. We have recently shown
      that angiotensin-converting enzyme (ACE), which generates profibrotic angiotensin
      II and inactivates antifibrotic bradykinin (BK), is upregulated in stenotic
      aortic valves. Here, we analyse the expression of neutral endopeptidase (NEP),
      another profibrotic and BK-degrading enzyme, and of BK receptors in aortic valves
      in AS. METHODS AND RESULTS: Stenotic aortic valves (n = 86) were obtained at
      valve replacement surgery and control valves (n = 13) at cardiac transplantation.
      Expression levels of NEP and BK type 1 and 2 receptors (BK-1R and BK-2R) in
      aortic valves and in isolated valvular myofibroblasts were analysed by real-time
      PCR and immunohistochemistry, and NEP activity was quantified by autoradiography.
      NEP, BK-1R, and BK-2R mRNA levels were higher in stenotic than in non-stenotic
      valves (P < 0.05 for each) and the respective proteins localized to valvular
      endothelial cells and myofibroblasts. In stenotic valves, the proteolytic
      activity of NEP was significantly increased (4.5-fold, P < 0.001), and tumour
      necrosis factor-alpha induced the expression of NEP in cultured myofibroblasts.
      Finally, treatment of cultured myofibroblasts with an NEP inhibitor
      (phosphoramidon) downregulated the expression of profibrotic transforming growth
      factor-beta1, whereas addition of BK decreased the expression of collagens I and
      III which was reversed by a BK-2R antagonist. CONCLUSION: NEP activity is
      increased in stenotic aortic valves in parallel with increased expression of BK
      receptors. The upregulation of NEP and BK-1R have the potential to promote
      valvular fibrosis and remodelling while the increase in BK-2R may represent a
      compensatory antifibrotic response. These findings add novel pathogenic insight
      and raise potential new therapeutic targets in AS.

PMID- 17507368
TI  - Mortality and morbidity from coronary heart disease attributable to passive
      smoking.
AB  - AIMS: Passive smoking is associated with increased risk of coronary heart disease
      (CHD). This study estimates CHD mortality and morbidity attributable to passive
      smoking in Germany and demonstrates variations in the number of estimated deaths
      depending on underlying assumptions. METHODS AND RESULTS: Prevalence of passive
      smoking from the German National Health Survey, CHD deaths from national
      mortality statistics, number of incident CHD cases, and relative risks from meta
      analyses were used to estimate mortality and morbidity from passive smoking
      applying the concept of population attributable risk. Sensitivity analyses were
      carried out to investigate the impact of different assumptions in terms of
      exposure definition, relative risk, and population at risk on estimated
      mortality. Exposure to environmental tobacco smoke (ETS) at home accounts for
      2148 [approximate 95% confidence interval (CI) 1471-2736] deaths from CHD and
      3776 (95% CI 2588-4800) incident CHD cases among non-smokers every year in
      Germany. In sensitivity analyses, consideration of exposure to ETS at work and at
      any location yielded 2597 (95% CI 1784-3295) and 8970 (95% CI 6252-11 243)
      attributable CHD deaths, respectively. Applying different populations at risk
      showed a range of 1174 (95% CI 803-1494) to 13 792 (95% CI 9655-17 225)
      attributable deaths from CHD. CONCLUSION: The estimated burden of passive smoking
      heavily depends on the definition of underlying parameters. Using an evidence
      based approach reveals a substantial burden of passive smoking in terms of CHD
      mortality and morbidity reflected by six CHD deaths and 10 incident CHD cases
      every day in Germany.

PMID- 17507369
TI  - Mass spectrometric analysis of the endogenous type I interleukin-1 (IL-1)
      receptor signaling complex formed after IL-1 binding identifies IL-1RAcP, MyD88,
      and IRAK-4 as the stable components.
AB  - We investigated the composition of the endogenous ligand-bound type I interleukin
      1 (IL-1) receptor (IL-1RI) signaling complex using immunoprecipitation and tandem
      mass spectrometry. Three proteins with approximate molecular masses of 60 (p60),
      36 (p36), and 90 kDa (p90) became phosphorylated after treatment with IL-1.
      Phosphorylation in vitro of p60 has been reported previously, but its identity
      was unknown. We showed using tandem mass spectrometry that p60 is identical to
      interleukin-1 receptor-associated kinase (IRAK)-4. MS also enabled detection of
      IL-1, IL-1RI, IL-1 receptor accessory protein (IL-1RAcP), and myeloid
      differentiation primary response protein 88 (MyD88) in the complex. The p60
      protein (IRAK-4) was the earliest component of the complex to be phosphorylated.
      Phosphorylated IRAK-4 from the receptor complex migrated more slowly in SDS-PAGE
      than its unphosphorylated form as did recombinant IRAK-4 autophosphorylated in
      vitro. Phosphorylation was restricted to serine and threonine residues. IRAK-4,
      p36, IL-1RAcP, and MyD88 bound to the liganded receptor within 15 s of activation
      by IL-1 and remained associated upon prolonged activation, suggesting that the
      signaling complex is very stable. The p90 phosphoprotein was only transiently
      associated with the receptor. This behavior and its size were consistent with it
      being IRAK-1. Our work revealed that liganding of IL-1RI causes its strong and
      stable association with IL-1RAcP, MyD88, and the previously unidentified protein
      p60 (IRAK-4). The only component of the IL-1RI signaling complex that dissociated
      is IRAK-1. Our study is therefore the first detailed description of the
      endogenous IL-1RI complex.

PMID- 17507370
TI  - Dynamic interplay between O-linked N-acetylglucosaminylation and glycogen
      synthase kinase-3-dependent phosphorylation.
AB  - O-GlcNAcylation on serine and threonine side chains of nuclear and cytoplasmic
      proteins is dynamically regulated in response to various environmental and
      biological stimuli. O-GlcNAcylation is remarkably similar to O-phosphorylation
      and appears to have a dynamic interplay with O-phosphate in cellular regulation.
      A systematic glycoproteomics analysis of the affects of inhibiting specific
      kinases on O-GlcNAcylation should help reveal both the global and specific
      dynamic relationships between these two abundant post-translational
      modifications. Here we report the O-GlcNAc perturbations in response to
      inhibition of glycogen synthase kinase-3 (GSK-3), a pivotal kinase involved in
      many signaling pathways. By combining immunoaffinity chromatography and SILAC
      (stable isotope labeling with amino acids in cell culture)-based quantitative
      mass spectrometry, we identified 45 potentially O-GlcNAcylated proteins.
      Quantitative measurements indicated that at least 10 proteins had an apparent
      increase of O-GlcNAcylation upon GSK-3 inhibition by lithium, whereas
      surprisingly 19 other proteins showed decreases. O-GlcNAcylation changes on a
      subset of the proteins were confirmed by follow-up experiments. By combining a
      new O-GlcNAc peptide enrichment method and beta-elimination followed by Michael
      addition with DTT, we also mapped the O-GlcNAc site (Ser-55) of vimentin, which
      showed an apparent increase of O-GlcNAcylation upon GSK-3 inhibition. Based on
      the MS data, we further investigated potential roles of O-GlcNAc on host cell
      factor-1, a transcription co-activator, and showed that dynamic regulation of O
      GlcNAcylation on host cell factor-1 influenced its subcellular distribution.
      Taken together, these data indicated the complex interplay between
      phosphorylation and O-GlcNAcylation that occurs within signaling networks.

PMID- 17507371
TI  - CD36 is important for fatty acid and cholesterol uptake by the proximal but not
      distal intestine.
AB  - CD36, a membrane protein that facilitates fatty acid uptake, is highly expressed
      in the intestine on the luminal surface of enterocytes. Cd36 null (Cd36(-/-))
      mice exhibit impaired chylomicron secretion but no overall lipid absorption
      defect. Because chylomicron production is most efficient proximally we examined
      whether CD36 function is important for proximal lipid absorption. CD36 levels
      followed a steep decreasing gradient along three equal-length, proximal to distal
      intestinal segments (S1-S3). Enterocytes isolated from the small intestines of
      Cd36(-/-) mice, when compared with wild type counterparts, exhibited reduced
      uptake of fatty acid (50%) and cholesterol (60%) in S1. The high affinity fatty
      acid uptake component was missing in Cd36(-/-) cells. Fatty acid incorporation
      into triglyceride and triglyceride secretion were also reduced in Cd36(-/-) S1
      enterocytes. In vivo, proximal absorption was monitored using mass spectrometry
      from oleic acid enrichment of S1 lipids, 90 min (active absorption) and 5 h
      (steady state) after intragastric olive oil (70% triolein). Oleate enrichment was
      50% reduced at 90 min in Cd36(-/-) tissue consistent with defective uptake
      whereas no differences were measured at 5 h. In Cd36(-/-) S1, mRNA for L-fabp,
      Dgat1, and apoA-IV was reduced. Protein levels for FATP4, SR-BI, and NPC1L1 were
      similar, whereas those for apoB48 and apoA-IV were significantly lower. A large
      increase in NPC1L1 was observed in Cd36(-/-) S2 and S3. The findings support the
      role of CD36 in proximal absorption of dietary fatty acid and cholesterol for
      optimal chylomicron formation, whereas CD36-independent mechanisms predominate in
      distal segments.

PMID- 17507372
TI  - A dominant-negative form of mouse SOX2 induces trophectoderm differentiation and
      progressive polyploidy in mouse embryonic stem cells.
AB  - SOX2 plays an important role in early embryogenesis by cooperating with OCT4 in
      regulating gene expression in fertilized eggs, yet the precise mechanism through
      which SOX2 accomplishes this important function remains poorly understood. Here,
      we describe the identification of two nuclear localization signals (NLS) in SOX2
      and the generation of a dominant-negative mutant (Dmu-mSox2) by mutating these
      two NLS in its high mobility group domain. Characterization of this mutant
      demonstrated that SOX2 shuttles between the cytoplasm and nucleus using these two
      NLS. The mutant has lost its ability to interact with OCT4, but remains competent
      to interact with wild-type SOX2. Functionally, Dmu-mSox2 is inactive and unable
      to cooperate with OCT4 in transactivating target promoters bearing its binding
      sites. However, Dmu-mSox2 is able to inhibit the activity of wild-type SOX2 and
      subsequently suppress the activity of downstream genes such as Oct4 and Nanog.
      When stably expressed in embryonic stem (ES) cells, Dmu-mSox2 triggered
      progressive doublings of cell ploidy (>8N), leading to differentiation into the
      trophectoderm lineage. Knockdown of Sox2 by small interfering RNA also induced
      trophectoderm differentiation and polyploid formation in mouse ES cells. These
      results suggest that SOX2 maintains stem cell pluripotency by shuttling between
      the nucleus and cytoplasm in cooperation with OCT4 to prevent trophectoderm
      differentiation and polyploid formation in ES cells.

PMID- 17507373
TI  - Mutational analysis of H3 and H4 N termini reveals distinct roles in nuclear
      import.
AB  - Core histones H3 and H4 are rapidly imported into the nucleus by members of the
      karyopherin (Kap)/importin family. We showed that H3 and H4 interact with
      Kap123p, histone acetyltransferase-B complex (HAT-B), and Asf1p in cytosol. In
      vivo analysis indicated that Kap123p is required for H3-mediated import, whereas
      H4 utilizes multiple Kaps including Kap123p. The evolutionary conservation of H3
      and H4 cytoplasmic acetylation led us to analyze the role of acetylation in
      nuclear transport. We determined that lysine 14 is critical for H3 NLS function
      in vivo and demonstrated that mutation of H3 lysine 14 to the acetylation-mimic
      glutamine decreased association with Kap123p in vitro. Several lysines in the H4
      NLS are important for its function. We showed that mutation of key lysines to
      glutamine resulted in a greater import defect than mutation to arginine,
      suggesting that positive charge promotes NLS function. Lastly we determined that
      six of ten N-terminal acetylation sites in H3 and H4 can be mutated to arginine,
      indicating that deposition acetylation is not absolutely necessary in vivo.
      However, the growth defect of these mutants suggests that acetylation does play
      an important role in import. These findings suggest a model where cytosolic
      histones bind import karyopherins prior to acetylation. Other factors are
      recruited to this complex such as HAT-B and Asf1p; these factors in turn promote
      acetylation. Acetylation may be important for modulating the interaction with
      transport factors and may play a role in the release of histones from
      karyopherins in the nucleus.

PMID- 17507374
TI  - Initiation of decay of Bacillus subtilis trp leader RNA.
AB  - Transcription termination in the leader region of the Bacillus subtilis trp
      operon is regulated by binding of the 11-mer TRAP complex to nascent trp RNA,
      which results in formation of a terminator structure. Rapid decay of trp leader
      RNA, which is required to release the TRAP complex and maintain a sufficient
      supply of free TRAP, is mediated by polynucleotide phosphorylase (PNPase). Using
      purified B. subtilis PNPase, we showed that, when TRAP was present, PNPase
      binding to the 3' end of trp leader RNA and PNPase digestion of trp leader RNA
      from the 3' end were inefficient. These results suggested that initiation of trp
      leader RNA may begin with an endonuclease cleavage upstream of the transcription
      terminator structure. Such cleavage was observed in vivo. Mutagenesis of
      nucleotides at the cleavage site abolished processing and resulted in a 4-fold
      increase in trp leader RNA half-life. This is the first mapping of a decay
      initiating endonuclease cleavage site on a native B. subtilis RNA.

PMID- 17507375
TI  - Strand opening-deficient Escherichia coli RNA polymerase facilitates
      investigation of closed complexes with promoter DNA: effects of DNA sequence and
      temperature.
AB  - Formation of the strand-separated, open complex between RNA polymerase and a
      promoter involves several intermediates, the first being the closed complex in
      which the DNA is fully base-paired. This normally short lived complex has been
      difficult to study. We have used a mutant Escherichia coli RNA polymerase,
      deficient in promoter DNA melting, and variants of the P(R) promoter of
      bacteriophage lambda to model the closed complex intermediate at physiologically
      relevant temperatures. Our results indicate that in the closed complex, RNA
      polymerase recognizes base pairs as double-stranded DNA even in the region that
      becomes single-stranded in the open complex. Additionally, a particular base pair
      in the -35 region engages in an important interaction with the RNA polymerase,
      and a DNase I-hypersensitive site, pronounced in the promoter DNA of the open
      complex, was not present. The effect of temperature on closed complex formation
      was found to be small over the temperature range from 15 to 37 degrees C. This
      suggests that low temperature complexes of wild type RNA polymerase and promoter
      DNA may adequately model the closed complex.

PMID- 17507376
TI  - Differential function of PTPalpha and PTPalpha Y789F in T cells and regulation of
      PTPalpha phosphorylation at Tyr-789 by CD45.
AB  - CD45 is a major membrane protein tyrosine phosphatase (PTP) expressed in T cells
      where it regulates the activity of Lck, a Src family kinase important for T cell
      receptor-mediated activation. PTPalpha is a more widely expressed transmembrane
      PTP that has been shown to regulate the Src family kinases, Src and Fyn, and is
      also present in T cells. Here, PTPalpha was phosphorylated at Tyr-789 in CD45(-)
      T cells but not in CD45(+) T cells suggesting that CD45 could regulate the
      phosphorylation of PTPalpha at this site. Furthermore, CD45 could directly
      dephosphorylate PTPalpha in vitro. Expression of PTPalpha and PTPalpha-Y789F in T
      cells revealed that the mutant had a reduced ability to decrease Fyn and Cbp
      phosphorylation, to regulate the kinase activity of Fyn, and to restore T cell
      receptor-induced signaling events when compared with PTPalpha. Conversely, this
      mutant had an increased ability to prevent Pyk2 phosphorylation and CD44-mediated
      cell spreading when compared with PTPalpha. These data demonstrate distinct
      activities of PTPalpha and PTPalpha-Y789F in T cells and identify CD45 as a
      regulator of PTPalpha phosphorylation at tyrosine 789 in T cells.

PMID- 17507377
TI  - Amino acid changes within antenna helix are responsible for different regulatory
      preferences of human glutamate dehydrogenase isozymes.
AB  - Human glutamate dehydrogenase (hGDH) exists in hGDH1 (housekeeping isozyme) and
      in hGDH2 (nerve-specific isozyme), which differ markedly in their allosteric
      regulation. Because they differ in only 16 of their 505 amino acids, the
      regulatory preferences must arise from amino acid residues that are not common
      between hGDH1 and hGDH2. To our knowledge none of the mutagenesis studies on the
      hGDH isozymes to date have identified the amino acid residues fully responsible
      for the different regulatory preferences between hGDH1 and hGDH2. In this study
      we constructed hGDH1(hGDH2(390-448))hGDH1 (amino acid segment 390-448 of hGDH1
      replaced by the corresponding hGDH2 segment) and hGDH2(hGDH1(390-448))hGDH2
      (amino acid segment 390-448 of hGDH2 replaced by the corresponding hGDH1 segment)
      by swapping the corresponding amino acid segments in hGDH1 and hGDH2. The
      chimeric enzymes by reciprocal swapping resulted in double mutations in amino
      acid sequences at 415 and 443 residues that are not common between hGDH1 and
      hGDH2 and are located in the C-terminal 48-residue "antenna" helix, which is
      thought to be part of the regulatory domain of mammalian GDHs. Functional
      analyses revealed that the doubly mutated chimeric enzymes almost completely
      acquired most of the different regulatory preferences between hGDH1 and hGDH2 for
      electrophoretic mobility, heat-stability, ADP activation, palmitoyl-CoA
      inhibition, and l-leucine activation, except for GTP inhibition. Our results
      indicate that substitutions of the residues in the antenna region may be
      important evolutionary changes that led to the adaptation of hGDH2 to the unique
      metabolic needs of the nerve tissue.

PMID- 17507378
TI  - Nucleotide excision repair eliminates unique DNA-protein cross-links from
      mammalian cells.
AB  - DNA-protein cross-links (DPCs) present a formidable obstacle to cellular
      processes because they are "superbulky" compared with the majority of chemical
      adducts. Elimination of DPCs is critical for cell survival because their
      persistence can lead to cell death or halt cell cycle progression by impeding DNA
      and RNA synthesis. To study DPC repair, we have used DNA methyltransferases to
      generate unique DPC adducts in oligodeoxyribonucleotides or plasmids to monitor
      both in vitro excision and in vivo repair. We show that HhaI DNA
      methyltransferase covalently bound to an oligodeoxyribonucleotide is not
      efficiently excised by using mammalian cell-free extracts, but protease digestion
      of the full-length HhaI DNA methyltransferase-DPC yields a substrate that is
      efficiently removed by a process similar to nucleotide excision repair (NER). To
      examine the repair of that unique DPC, we have developed two plasmid-based in
      vivo assays for DPC repair. One assay shows that in nontranscribed regions, DPC
      repair is greater than 60% in 6 h. The other assay based on host cell
      reactivation using a green fluorescent protein demonstrates that DPCs in
      transcribed genes are also repaired. Using Xpg-deficient cells (NER-defective)
      with the in vivo host cell reactivation assay and a unique DPC indicates that NER
      has a role in the repair of this adduct. We also demonstrate a role for the 26 S
      proteasome in DPC repair. These data are consistent with a model for repair in
      which the polypeptide chain of a DPC is first reduced by proteolysis prior to
      NER.

PMID- 17507379
TI  - Analysis of a parallel branch in the mitomycin biosynthetic pathway involving the
      mitN-encoded aziridine N-methyltransferase.
AB  - Mitomycin C is a natural product with potent alkylating activity, and it is an
      important anticancer drug and antibiotic. mitN, one of three genes with high
      similarity to methyltransferases, is located within the mitomycin biosynthetic
      gene cluster. An inframe deletion in mitN of the mitomycin biosynthetic pathway
      was generated in Streptomyces lavendulae to produce the DHS5373 mutant strain.
      Investigation of DHS5373 revealed continued production of mitomycin A and
      mitomycin C in addition to the accumulation of a new mitomycin analog, 9-epi
      mitomycin C. The mitN gene was overexpressed in Escherichia coli, and the
      histidine-tagged protein (MitN) was purified to homogeneity. Reaction of 9-epi
      mitomycin C with MitN in the presence of S-adenosylmethionine yielded mitomycin E
      showing that the enzyme functions as an aziridine N-methyltransferase. Likewise,
      MitN was also shown to convert mitomycin A to mitomycin F under the same reaction
      conditions. We conclude that MitN plays an important role in a parallel
      biosynthetic pathway leading to the subclass of mitomycins with 9alpha
      stereochemistry but is not involved directly in the biosynthesis of mitomycins A
      and C.

PMID- 17507380
TI  - Formation of a dinitrosyl iron complex by NorA, a nitric oxide-binding di-iron
      protein from Ralstonia eutropha H16.
AB  - In Ralstonia eutropha H16, two genes, norA and norB, form a dicistronic operon
      that is controlled by the NO-responsive transcriptional regulator NorR. NorB has
      been identified as a membrane-bound NO reductase, but the physiological function
      of NorA is unknown. We found that, in a NorA deletion mutant, the promoter
      activity of the norAB operon was increased 3-fold, indicating that NorA
      attenuates activation of NorR. NorA shows limited sequence similarity to the
      oxygen carrier hemerythrin, which contains a di-iron center. Indeed, optical and
      EPR spectroscopy of purified NorA revealed the presence of a di-iron center,
      which binds oxygen in a similar way as hemerythrin. Diferrous NorA binds two
      molecules of NO maximally. Unexpectedly, binding of NO to the diferrous NorA
      required an external reductant. Two different NorA-NO species could be resolved.
      A minor species (up to 20%) showed an S = (1/2) EPR signal with g( perpendicular)
      = 2.041, and g( parallel) = 2.018, typical of a paramagnetic dinitrosyl iron
      complex. The major species was EPR-silent, showing characteristic signals at 420
      nm and 750 nm in the optical spectrum. This species is proposed to represent a
      novel dinitrosyl iron complex of the form Fe(2+)-[NO](2)(2-), i.e. NO is bound as
      NO(-). The NO binding capacity of NorA in conjunction with its high cytoplasmic
      concentration (20 mum) suggests that NorA regulates transcription by lowering the
      free cytoplasmic concentration of NO.

PMID- 17507381
TI  - Pancreatic insulin secretion in rats fed a soy protein high fat diet depends on
      the interaction between the amino acid pattern and isoflavones.
AB  - Obesity is frequently associated with the consumption of high carbohydrate/fat
      diets leading to hyperinsulinemia. We have demonstrated that soy protein (SP)
      reduces hyperinsulinemia, but it is unclear by which mechanism. Thus, the purpose
      of the present work was to establish whether SP stimulates insulin secretion to a
      lower extent and/or reduces insulin resistance, and to understand its molecular
      mechanism of action in pancreatic islets of rats with diet-induced obesity. Long
      term consumption of SP in a high fat (HF) diet significantly decreased serum
      glucose, free fatty acids, leptin, and the insulin:glucagon ratio compared with
      animals fed a casein HF diet. Hyperglycemic clamps indicated that SP stimulated
      insulin secretion to a lower extent despite HF consumption. Furthermore, there
      was lower pancreatic islet area and insulin, SREBP-1, PPARgamma, and GLUT-2 mRNA
      abundance in comparison with rats fed the casein HF diet. Euglycemic
      hyperinsulinemic clamps showed that the SP diet prevented insulin resistance
      despite consumption of a HF diet. Incubation of pancreatic islets with
      isoflavones reduced insulin secretion and expression of PPARgamma. Addition of
      amino acids resembling the plasma concentration of rats fed casein stimulated
      insulin secretion; a response that was reduced by the presence of isoflavones,
      whereas the amino acid pattern resembling the plasma concentration of rats fed SP
      barely stimulated insulin release. Infusion of isoflavones during the
      hyperglycemic clamps did not stimulate insulin secretion. Therefore, isoflavones
      as well as the amino acid pattern seen after SP consumption stimulated insulin
      secretion to a lower extent, decreasing PPARgamma, GLUT-2, and SREBP-1
      expression, and ameliorating hyperinsulinemia observed during obesity.

PMID- 17507382
TI  - Human Xip1 (C2orf13) is a novel regulator of cellular responses to DNA strand
      breaks.
AB  - DNA strand breaks arise continuously as the result of intracellular metabolism
      and in response to a multitude of genotoxic agents. To overcome such challenges
      to genomic stability, cells have evolved genome surveillance pathways that detect
      and repair damaged DNA in a coordinated fashion. Here we identify the previously
      uncharacterized human protein Xip1 (C2orf13) as a novel component of the
      checkpoint response to DNA strand breaks. Green fluorescent protein-tagged Xip1
      was rapidly recruited to sites of DNA breaks, and this accumulation was dependent
      on a novel type of zinc finger motif located in the C terminus of Xip1. The
      initial recruitment kinetics of Xip1 closely paralleled that of XRCC1, a central
      organizer of single strand break (SSB) repair, and its accumulation was both
      delayed and sustained when the detection of SSBs was abrogated by inhibition of
      PARP-1. Xip1 and XRCC1 stably interacted through recognition of CK2
      phosphorylation sites in XRCC1 by the Forkhead-associated (FHA) domain of Xip1,
      and XRCC1 was required to maintain steady-state levels of Xip1. Moreover, Xip1
      was phosphorylated on Ser-116 by ataxia telangiectasia-mutated in response to
      ionizing radiation, further underscoring the potential importance of Xip1 in the
      DNA damage response. Finally, depletion of Xip1 significantly decreased the
      clonogenic survival of cells exposed to DNA SSB- or double strand break-inducing
      agents. Collectively, these findings implicate Xip1 as a new regulator of genome
      maintenance pathways, which may function to organize DNA strand break repair
      complexes at sites of DNA damage.

PMID- 17507383
TI  - On the reassessment of thermal neutron doses in TLD-100 by measuring the residual
      dose.
AB  - By employing second readouts and the Phototransferred thermoluminescence (PTTL)
      method, high doses may be reassessed on the basis of residual dose information.
      It was shown in the past that for TLD-100, gamma doses can be reassessed by using
      a simple and efficient method, which consists of expanding the heating time to 30
      s. In the present study, the 'extended time' method and the PTTL residual dose
      evaluations are used for reassessing thermal neutron doses when using TLD-100
      crystals. Reassessment characteristics are presented for relatively low thermal
      neutron doses, in the range between approximately 1 and 18 mSv gamma dose
      equivalent.

PMID- 17507384
TI  - Determination of the neutron fluence spectra in the neutron therapy room of
      KIRAMS.
AB  - High energy proton induced neutron fluence spectra were determined at the Korea
      Institute of Radiological and Medical Sciences (KIRAMS) using an extended Bonner
      Sphere (BS) set from the Korea Atomic Energy Research Institute (KAERI) in a
      series of measurements to quantify the neutron field. At the facility of the MC50
      cyclotron of KIRAMS, two Be targets of different thicknesses, 1.0 and 10.5 mm,
      were bombarded by 35 and 45-MeV protons to produce six kinds of neutron fields,
      which were classified according to the measurement position and the use or no use
      of a beam collimator such as the gantry of the neutron therapy unit. In order to
      obtain a priori information to unfold the measured BS data the MCNPX code was
      used to calculate the neutron spectrum, and the influence of the surrounding
      materials for cooling the target assembly were also reviewed through this
      calculation. Some dosimetric quantities were determined by using the spectra
      determined in this measurement. Dose equivalent rates of these neutron fields
      ranged from 0.21 to 5.66 mSv h(-1)nA(-1) and the neutron yields for a thick Be
      target were 3.05 and 4.77% in the case of using a 35 and a 45-MeV proton,
      respectively.

PMID- 17507386
TI  - A follow-up study of women who donated oocytes to known recipient couples for
      altruistic reasons.
AB  - BACKGROUND: Current legislation in Canada allows for only altruistic gamete
      donation. Limited clinical data are available on the emotional and psychological
      impact of altruistic oocyte donation on known donors. METHODS: Seventeen women
      who had donated oocytes to known parties without financial compensation agreed to
      receive the oocyte donation questionnaire (ODQ) to explore the psychological
      domains of altruistic oocyte donation. RESULTS: Thirteen ODQ were returned,
      giving a response rate of 76%. All subjects indicated that they were primarily
      motivated by a 'desire to give and help' the recipient couple. Most subjects did
      not find the donation decision difficult but some found the post-donation
      psychological adjustments challenging. Subjects also indicated that mandatory
      counselling on the psychological implications of oocyte donation was an important
      component of cycle preparation. The majority of subjects had disclosed the
      donation to others and felt that disclosure to the presumptive child was
      essential. CONCLUSIONS: The findings provide clinical materials for
      conceptualizing the dynamics entailed by known altruistic oocyte donation, with
      regards to motivation, relationship implications, donor satisfaction and plans
      for disclosure. The data support the provision of psycho-social support services
      to help donors dealing with any residual emotional difficulties regardless of the
      outcome of oocyte donation.

PMID- 17507385
TI  - Sperm suspension is a highly ultrasonically visible material: a novel model to
      study uterine activity.
AB  - BACKGROUND: The aims of this study were to find an ultrasonically echogenic
      material to study the uterine activity, and to test whether closing the vaginal
      speculum on the cervix prevents the displacement of the injected material.
      METHODS: A concentrated sperm suspension was used as an ultrasonically visible
      material. Forty-five women undergoing intrauterine insemination were randomized
      into: open speculum group (n=23) and closed speculum group (n=22). Mimicking
      embryo transfer, 50 ul of concentrated sperm suspension was injected intrauterine
      while the vaginal speculum was open in 23 patients. In the other group, the two
      blades of the vaginal speculum were closed on the cervix, then 50 ul of
      concentrated sperm suspension was injected. The ultrasonically visible material
      was observed in the uterine cavity for 10 min during which the procedure was
      video-recorded. RESULTS: The injected sperm suspension was clearly visible in all
      cases. In the closed speculum group, the echogenic droplet remained in the upper
      uterine segment in 18 cases (82%) and moved towards the lower uterine segment in
      six cases (18%). In the open speculum group, the echogenic droplet remained in
      the upper uterine segment in only six cases (26%) and it moved towards the lower
      uterine segment and passed through the cervical canal in 17 cases (74%).
      CONCLUSIONS: For the first time in the medical literature, a concentrated sperm
      suspension was used as an ultrasonographically visible material to study uterine
      activity. Closing the portio-vaginalis of the cervix prevents the displacement of
      the injected material.

PMID- 17507387
TI  - Application of proteomic methods for identification of sperm immunogenic
      antigens.
AB  - Although the immunogenic properties of sperm have been explored for a few
      decades, none of the antigens studied so far appears to be an effective target,
      to inhibit the fertilization process or shown the full spectrum of sperm
      antigenic potential. Antisperm antibodies (ASA) collected from infertile
      individuals and prepubertal boys with cryptorchidism together with two
      dimensional (2D) electrophoresis have been employed. Immunoreactive antigens were
      cored from silver stained 2D gels and analyzed by mass spectrometry (MS). The
      obtained sequences were searched in the published protein databases. Altogether,
      35 different sperm entities were identified in accessible protein databases, out
      of which 10 appeared to be sperm-specific. Additionally, 6 amino acid sequences
      indicated novel (hypothetical) proteins. Seventeen sperm entities were detected
      in sera samples from immune infertile males and 18 entities in ASA-positive
      seminal plasma (SP). Interestingly, we identified a few sperm structures, none of
      them sperm specific in sera samples from infertile females. Although, infertile
      males from whom the ASA-positive SP samples were obtained, did not have ASA in
      their circulation, the range of sperm antigens detected by systematic and local
      antibodies overlapped to a great extent (six identical entities). Sera samples
      from prepubertal boys allowed to show antigens, previously thought to be only
      present on mature sperm. Three out of four detected were sperm-specific. Using
      serum and SP of ASA-positive infertile adults and sera samples of prepubertal
      boys with testicular failure, we have extended the range of known, immunogenic
      sperm proteins as well as identified some novel antigens (n=6) of human sperm for
      further characterization.

PMID- 17507388
TI  - Alternative oxidase involvement in cold stress response of Arabidopsis thaliana
      fad2 and FAD3+ cell suspensions altered in membrane lipid composition.
AB  - To investigate how the fatty acid composition of membrane lipids influences cell
      growth and mitochondrial respiration, in particular the expression and capacity
      of alternative oxidase (AOX), under cold stress, we used the Arabidopsis thaliana
      fad2 knockout and FAD3+ -overexpressing cultured cells lines affected in
      extrachloroplastic fatty acid desaturation activities. At 22 degrees C, fad2
      mitochondria exhibited a low polyunsaturated fatty acid content and low protein
      to lipid ratio, while mitochondria from FAD3+ were enriched in linolenic acid and
      in total membrane protein. As a consequence, both mutants showed a higher
      membrane microviscosity than the wild type. After exposure to 9 degrees C, FAD3+
      mitochondria exhibited lower microviscosity and lower rigidification upon a
      temperature downshift than fad2. Furthermore, the extent of reduction of cell
      growth and respiratiory rates in the phosphorylating state was positively related
      to the cold sensitivity of each cell line, being more pronounced in fad2 that in
      the wild type, whereas the stability of those parameters reflected the cold
      resistance of FAD3+. In contrast, an increase in AOX capacity was observed in the
      three cell lines at 9 degrees C. These inductions were correlated to AOX protein
      amounts and seem to result from an accumulation of AOX1c transcripts in the three
      cell lines and of AOX1a transcripts in wild-type and fad2 cells. The fact that
      there is no direct relationship between the degree of cold tolerance of each cell
      line and their ability to enhance their AOX capacity suggests that the
      participation of AOX in the response of Arabidopsis cells to cold stress does not
      necessarily favor cold tolerance.

PMID- 17507389
TI  - Phototropins and neochrome1 mediate nuclear movement in the fern Adiantum
      capillus-veneris.
AB  - In gametophytic cells (prothalli) of the fern Adiantum capillus-veneris, nuclei
      as well as chloroplasts change their position according to light conditions.
      Nuclei reside on anticlinal walls in darkness and move to periclinal or
      anticlinal walls under weak or strong light conditions, respectively. Here we
      reveal that red light-induced nuclear movement is mediated by neochrome1 (neo1),
      blue light-induced movement is redundantly mediated by neo1, phototropin2 (phot2)
      and possibly phot1, and dark positioning of both nuclei and chloroplasts is
      mediated by phot2. Thus, both the nuclear and chloroplast photorelocation
      movements share common photoreceptor systems.

PMID- 17507390
TI  - Effect of polyethylene glycols on the function and structure of thiol proteases.
AB  - Thiol proteases are industrially significant proteins with catalytic efficiency.
      The effect of low, medium and high molecular-weight poly (ethylene glycol) (PEG-
      400, 6000 and 20000) on the stability of thiol proteases (papain, bromelain and
      chymopapain) has been studied by activity measurements using synthetic substrate.
      Structural studies performed on papain by far UV circular dichroism spectroscopic
      measurements indicate that there is loss in secondary structure of the protein in
      presence of increasing concentration of PEGs. Intrinsic fluorescence measurements
      lead us to conclude that tryptophan residues of protein encounter non-polar
      microenvironment in presence of PEG solvent while acrylamide quenching shows
      greater accessibility of tryptophan residues of papain in presence of PEGs.
      Extrinsic fluorescence measurements lead us to conclude that PEGs bind to the
      hydrophobic sites on the protein and thus destabilize it. Thermal denaturation
      studies show that melting temperature of papain is decreased in presence of PEGs.
      Possible mechanism of destabilization is discussed next. The results imply that
      caution must be exercised in the use of PEGs with thiol proteases or hydrophobic
      proteins in general, for different industrial applications, even at room
      temperature.

PMID- 17507391
TI  - Localized VEGF signaling from ectoderm to mesenchyme cells controls morphogenesis
      of the sea urchin embryo skeleton.
AB  - During development, cell migration plays an important role in morphogenetic
      processes. The construction of the skeleton of the sea urchin embryo by a small
      number of cells, the primary mesenchyme cells (PMCs), offers a remarkable model
      to study cell migration and its involvement in morphogenesis. During
      gastrulation, PMCs migrate and become positioned along the ectodermal wall
      following a stereotypical pattern that determines skeleton morphology. Previous
      studies have shown that interactions between ectoderm and PMCs regulate several
      aspects of skeletal morphogenesis, but little is known at the molecular level.
      Here we show that VEGF signaling between ectoderm and PMCs is crucial in this
      process. The VEGF receptor (VEGFR) is expressed exclusively in PMCs, whereas VEGF
      expression is restricted to two small areas of the ectoderm, in front of the
      positions where the ventrolateral PMC clusters that initiate skeletogenesis will
      form. Overexpression of VEGF leads to skeletal abnormalities, whereas inhibition
      of VEGF/VEGFR signaling results in incorrect positioning of the PMCs,
      downregulation of PMC-specific genes and loss of skeleton. We present evidence
      that localized VEGF acts as both a guidance cue and a differentiation signal,
      providing a crucial link between the positioning and differentiation of the
      migrating PMCs and leading to morphogenesis of the embryonic skeleton.

PMID- 17507392
TI  - Actin-dependent cytoplasmic streaming in C. elegans oogenesis.
AB  - Oocytes in the C. elegans gonad enlarge rapidly. During the stage of enlargement,
      they are transcriptionally quiescent, and it is not understood how they acquire
      large quantities of materials such as mRNA and protein. Enlarging oocytes are
      connected via cytoplasmic bridges to a large, younger population of
      transcriptionally active germ cells at various stages of mitosis and meiosis. We
      show here that there is a general streaming of gonad cytoplasm towards and into
      the enlarging oocytes, originating primarily from pachytene-stage germ cells.
      Because previous studies suggested that most or all of the pachytene germ cells
      have the potential to differentiate into oocytes, the pachytene cells appear to
      function transiently as nurse cells. Somatic gonadal cells that surround the germ
      cells do not appear essential for streaming. Instead, materials appear to be
      pulled into oocytes by forces generated either in, or adjacent to, the enlarging
      oocytes themselves. Streaming appears to be driven by the actomyosin
      cytoskeleton, although we show that populations of both microfilaments and
      microtubules are oriented in the direction of flow. Our study shows that oocyte
      enlargement in C. elegans differs significantly from that in Drosophila, where a
      small number of specialized nurse cells expel their contents into the enlarging
      oocyte.

PMID- 17507393
TI  - Distinct functions of the major Fgf8 spliceform, Fgf8b, before and during mouse
      gastrulation.
AB  - The vertebrate Fgf8 gene produces multiple protein isoforms by alternative
      splicing. Two evolutionarily conserved spliceforms, Fgf8a and Fgf8b, exhibit
      distinct bioactivities, with Fgf8b having a more potent inductive activity due to
      higher affinity for Fgf receptors. To investigate the in vivo requirement for
      Fgf8b, we created a splice-site mutation abolishing Fgf8b expression in mice.
      Analysis of this mutant has uncovered a novel function of Fgf8 signaling before
      the onset of gastrulation. We show that the loss of Fgf8b disrupts the induction
      of the brachyury gene in the pregastrular embryo and, in addition, disrupts the
      proper alignment of the anteroposterior axis with the shape of the embryo and the
      uterine axes at embryonic day (E) 6.5. Importantly, Fgf8-null embryos display the
      same phenotype as Fgf8b-deficient embryos at E6.5, demonstrating that signaling
      by Fgf8b is specifically required for development of the pregastrular embryo. By
      contrast, during gastrulation, Fgf8a can partially compensate for the loss of
      Fgf8b in mesoderm specification. We show that an increased level of Fgf8a
      expression, which leads to Fgf4 expression in the primitive streak, can also
      promote mesoderm migration in the absence of Fgf8b. Therefore, different Fgf
      signals may have distinct requirements for the morphogenesis and gene regulation
      before and during gastrulation. Importantly, our findings implicate Fgf8 in the
      morphogenetic process that establishes the defined relationship between the axes
      of the embryo and the uterus at the beginning of gastrulation, a perplexing
      phenomenon discovered two decades ago.

PMID- 17507394
TI  - Progressive activation of Delta-Notch signaling from around the blastopore is
      required to set up a functional caudal lobe in the spider Achaearanea
      tepidariorum.
AB  - In the development of most arthropods, the caudal region of the elongating germ
      band (the growth zone) sequentially produces new segments. Previous work with the
      spider Cupiennius salei suggested involvement of Delta-Notch signaling in
      segmentation. Here, we report that, in the spider Achaearanea tepidariorum, the
      same signaling pathway exerts a different function in the presumptive caudal
      region before initiation of segmentation. In the developing spider embryo, the
      growth zone becomes morphologically apparent as a caudal lobe around the closed
      blastopore. We found that, preceding caudal lobe formation, transcripts of a
      Delta homolog, At-Delta, are expressed in evenly spaced cells in a small area
      covering the closing blastopore and then in a progressively wider area of the
      germ disc epithelium. Cells with high At-Delta expression are likely to be
      prospective mesoderm cells, which later express a twist homolog, At-twist, and
      individually internalize. Cells remaining at the surface begin to express a
      caudal homolog, At-caudal, to differentiate as caudal ectoderm. Knockdown of At
      Delta by parental RNA interference results in overproduction of At-twist
      expressing mesoderm cells at the expense of At-caudal-expressing ectoderm cells.
      This condition gives rise to a disorganized caudal region that fails to pattern
      the opisthosoma. In addition, knockdown of Notch and Suppressor of Hairless
      homologs produces similar phenotypes. We suggest that, in the spider, progressive
      activation of Delta-Notch signaling from around the blastopore leads to
      stochastic cell fate decisions between mesoderm and caudal ectoderm through a
      process of lateral inhibition to set up a functional caudal lobe.

PMID- 17507395
TI  - Hand2 is necessary for terminal differentiation of enteric neurons from crest
      derived precursors but not for their migration into the gut or for formation of
      glia.
AB  - Hand genes encode basic helix-loop-helix transcription factors that are expressed
      in the developing gut, where their function is unknown. We now report that
      enteric Hand2 expression is limited to crest-derived cells, whereas Hand1
      expression is restricted to muscle and interstitial cells of Cajal. Hand2 is
      developmentally regulated and is intranuclear in precursors but cytoplasmic in
      neurons. Neurons develop in explants from wild-type but not Hand2(-/-) bowel,
      although, in both, crest-derived cells are present and glia arise. Similarly,
      small interfering RNA (siRNA) silencing of Hand2 in enteric crest-derived cells
      prevents neuronal development. Terminally differentiated enteric neurons do not
      develop after conditional inactivation of Hand2 in migrating crest-derived cells;
      nevertheless, conditional Hand2 inactivation does not prevent precursors from
      expressing early neural markers. We suggest that enteric neuronal development
      occurs in stages and that Hand2 expression is required for terminal
      differentiation but not for precursors to enter the neuronal lineage.

PMID- 17507396
TI  - The role of Dpp and its inhibitors during eggshell patterning in Drosophila.
AB  - The Drosophila eggshell is patterned by the combined action of the epidermal
      growth factor [EGF; Gurken (Grk)] and transforming growth factor beta [TGF-beta;
      Decapentaplegic (Dpp)] signaling cascades. Although Grk signaling alone can
      induce asymmetric gene expression within the follicular epithelium, here we show
      that the ability of Grk to induce dorsoventral polarity within the eggshell
      strictly depends on Dpp. Dpp, however, specifies at least one anterior region of
      the eggshell in the absence of Grk. Dpp forms an anteriorposterior morphogen
      gradient within the follicular epithelium and synergizes with the dorsoventral
      gradient of Grk signaling. High levels of Grk and Dpp signaling induce the
      operculum, whereas lower levels of both pathways induce the dorsal appendages. We
      provide evidence that the crosstalk between both pathways occurs at least at two
      levels. First, Dpp appears to directly enhance the levels of EGF pathway activity
      within the follicular epithelium. Second, Dpp and EGF signaling collaborate in
      controlling the expression of Dpp inhibitors. One of these inhibitors is
      Drosophila sno (dSno), a homolog of the Ski/Sno family of vertebrate proto
      oncogenes, which synergizes with daughters against dpp and brinker to set the
      posterior and lateral limits of the region, giving rise to dorsal follicle cells.

PMID- 17507397
TI  - Cdk5 is required for multipolar-to-bipolar transition during radial neuronal
      migration and proper dendrite development of pyramidal neurons in the cerebral
      cortex.
AB  - The mammalian cerebral cortex consists of six layers that are generated via
      coordinated neuronal migration during the embryonic period. Recent studies
      identified specific phases of radial migration of cortical neurons. After the
      final division, neurons transform from a multipolar to a bipolar shape within the
      subventricular zone-intermediate zone (SVZ-IZ) and then migrate along radial
      glial fibres. Mice lacking Cdk5 exhibit abnormal corticogenesis owing to neuronal
      migration defects. When we introduced GFP into migrating neurons at E14.5 by in
      utero electroporation, we observed migrating neurons in wild-type but not in
      Cdk5(-/-) embryos after 3-4 days. Introduction of the dominant-negative form of
      Cdk5 into the wild-type migrating neurons confirmed specific impairment of the
      multipolar-to-bipolar transition within the SVZ-IZ in a cell-autonomous manner.
      Cortex-specific Cdk5 conditional knockout mice showed inverted layering of the
      cerebral cortex and the layer V and callosal neurons, but not layer VI neurons,
      had severely impaired dendritic morphology. The amount of the dendritic protein
      Map2 was decreased in the cerebral cortex of Cdk5-deficient mice, and the axonal
      trajectory of cortical neurons within the cortex was also abnormal. These results
      indicate that Cdk5 is required for proper multipolar-to-bipolar transition, and a
      deficiency of Cdk5 results in abnormal morphology of pyramidal neurons. In
      addition, proper radial neuronal migration generates an inside-out pattern of
      cerebral cortex formation and normal axonal trajectories of cortical pyramidal
      neurons.

PMID- 17507398
TI  - The generation of adipocytes by the neural crest.
AB  - Fat cells (adipocytes) develop from adipocyte precursor cells (preadipocytes)
      that themselves derive from mesenchymal progenitors. Although the events
      controlling preadipocyte differentiation into mature adipocytes have been largely
      explored, the mechanisms that direct mesenchymal progenitors down the adipocyte
      pathway remain unknown. Similarly, although adipocytes are generally thought to
      derive from mesoderm, key information is lacking regarding the origin and the
      development of the adipose tissue during embryogenesis. The aim of this study was
      to gain insight into the ontogeny of fat cells, both in mouse embryonic stem
      (mES) cell-derived cultures and during normal development. We first used
      genetically engineered mES cells to produce and select ES cell-derived
      neuroepithelial progenitors and showed that neuroectoderm, rather than mesoderm,
      may be a source of adipocytes in mES cell-derived cultures. We then used primary
      and secondary cultures of developing quail neural crest (NC) cells to demonstrate
      that NC cells are able, upon stimulation with defined factors, to differentiate
      into adipocytes, thus providing a powerful system to study the earliest stages of
      adipocyte differentiation. Finally, we mapped NC derivatives in vivo using Cre
      mediated recombination in transgenic mice and demonstrated that a subset of
      adipocytes originates from the NC during normal development.

PMID- 17507399
TI  - On the carapacial ridge in turtle embryos: its developmental origin, function and
      the chelonian body plan.
AB  - The chelonian carapace is composed of dorsolaterally expanded ribs; an
      evolutionary change in the rib-patterning program is assumed to be related to
      this novelty. Turtle embryos exhibit a longitudinal ridge called the carapacial
      ridge (CR) on the flank, and its histological resemblance to the apical
      ectodermal ridge of the limb bud implies its inductive activity in the unique
      patterning of the ribs. We studied the Chinese soft-shelled turtle, Pelodiscus
      sinensis, and confirmed by labeling with a lipophilic dye, DiI, that the CR
      contains the somite-derived dermis and that it is a unique structure among
      amniotes. Using electroporation of a dominant-negative form of LEF-1, the CR
      specific gene, we showed that CR-specific genes function in the growth and
      maintenance of the CR. Microcauterization or implantation of the CR did not
      change the dorsoventral pattern of the ribs, and only their fan-shaped pattern
      was arrested by CR removal. We conclude that the CR is a true embryonic novelty
      among amniotes and, because of the specific expression of regulatory genes, it
      functions in the marginal growth of the carapacial primordium, thereby inducing
      the fan-shaped arrangement of the ribs.

PMID- 17507400
TI  - Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential
      for liver and pancreas development.
AB  - The liver and pancreas are specified from the foregut endoderm through an
      interaction with the adjacent mesoderm. However, the earlier molecular mechanisms
      that establish the foregut precursors are largely unknown. In this study, we have
      identified a molecular pathway linking gastrula-stage endoderm patterning to
      organ specification. We show that in gastrula and early-somite stage Xenopus
      embryos, Wnt/beta-catenin activity must be repressed in the anterior endoderm to
      maintain foregut identity and to allow liver and pancreas development. By
      contrast, high beta-catenin activity in the posterior endoderm inhibits foregut
      fate while promoting intestinal development. Experimentally repressing beta
      catenin activity in the posterior endoderm was sufficient to induce ectopic organ
      buds that express early liver and pancreas markers. beta-catenin acts in part by
      inhibiting expression of the homeobox gene hhex, which is one of the earliest
      foregut markers and is essential for liver and pancreas development. Promoter
      analysis indicates that beta-catenin represses hhex transcription indirectly via
      the homeodomain repressor Vent2. Later in development, beta-catenin activity has
      the opposite effect and enhances liver development. These results illustrate that
      turning Wnt signaling off and on in the correct temporal sequence is essential
      for organ formation, a finding that might directly impact efforts to
      differentiate liver and pancreas tissue from stem cells.

PMID- 17507401
TI  - Stem cells and their niche: an inseparable relationship.
AB  - A recent Keystone symposium on 'Stem Cell Interactions with their
      Microenvironmental Niche' was organized by David T. Scadden and Allan C.
      Spradling. The meeting was held in conjunction with another Keystone symposium,
      'Stem Cells and Cancer', at Keystone, Colorado. Among the work that was presented
      at this meeting, scientists presented data that advances our understanding of the
      contribution that the niche makes to stem cell maintenance. Novel types of stem
      cells and niches were also reported and new findings that clarify our
      understanding of the molecular mechanisms that regulate and maintain stem cells
      were presented.

PMID- 17507402
TI  - The FERM protein Epb4.1l5 is required for organization of the neural plate and
      for the epithelial-mesenchymal transition at the primitive streak of the mouse
      embryo.
AB  - During early mouse development, a single-layered epithelium is transformed into
      the three germ layers that are the basis of the embryonic body plan. Here we
      describe an ENU-induced mutation, limulus (lulu), which disrupts gastrulation and
      the organization of all three embryonic germ layers. Positional cloning and
      analysis of additional alleles show that lulu is a null allele of the FERM-domain
      gene erythrocyte protein band 4.1-like 5 (Epb4.1l5). During gastrulation, some
      cells in lulu mutants are trapped in the primitive streak at an intermediate
      stage of the epithelial-mesenchymal transition; as a result, the embryos have
      very little paraxial mesoderm. Epithelial layers of the later lulu embryo are
      also disrupted: definitive endoderm is specified but does not form a gut tube,
      and the neural plate is broad and forms ectopic folds rather than closing to make
      the neural tube. In contrast to zebrafish and Drosophila, in which orthologs of
      Epb4.1l5 control the apical localization and activity of Crumbs proteins, mouse
      Crumbs proteins are localized normally to the apical surface of the lulu mutant
      epiblast and neural plate. However, the defects in both the lulu primitive streak
      and neural plate are associated with disruption of the normal organization of the
      actin cytoskeleton. We propose that mouse Lulu (Epb4.1l5) helps anchor the actin
      myosin contractile machinery to the membrane to allow the dynamic rearrangements
      of epithelia that mediate embryonic morphogenesis.

PMID- 17507403
TI  - Different Wnt signals act through the Frizzled and RYK receptors during
      Drosophila salivary gland migration.
AB  - Guided cell migration is necessary for the proper function and development of
      many tissues, one of which is the Drosophila embryonic salivary gland. Here we
      show that two distinct Wnt signaling pathways regulate salivary gland migration.
      Early in migration, the salivary gland responds to a WNT4-Frizzled signal for
      proper positioning within the embryo. Disruption of this signal, through
      mutations in Wnt4, frizzled or frizzled 2, results in misguided salivary glands
      that curve ventrally. Furthermore, disruption of downstream components of the
      canonical Wnt pathway, such as dishevelled or Tcf, also results in ventrally
      curved salivary glands. Analysis of a second Wnt signal, which acts through the
      atypical Wnt receptor Derailed, indicates a requirement for Wnt5 signaling late
      in salivary gland migration. WNT5 is expressed in the central nervous system and
      acts as a repulsive signal, needed to keep the migrating salivary gland on
      course. The receptor for WNT5, Derailed, is expressed in the actively migrating
      tip of the salivary glands. In embryos mutant for derailed or Wnt5, salivary
      gland migration is disrupted; the tip of the gland migrates abnormally toward the
      central nervous system. Our results suggest that both the Wnt4-frizzled pathway
      and a separate Wnt5-derailed pathway are needed for proper salivary gland
      migration.

PMID- 17507404
TI  - Enabled plays key roles in embryonic epithelial morphogenesis in Drosophila.
AB  - Studies in cultured cells and in vitro have identified many actin regulators and
      begun to define their mechanisms of action. Among these are Enabled (Ena)/VASP
      proteins, anti-Capping proteins that influence fibroblast migration, growth cone
      motility, and keratinocyte cell adhesion in vitro. However, partially redundant
      family members in mammals and maternal Ena contribution in Drosophila previously
      prevented assessment of the roles of Ena/VASP proteins in embryonic morphogenesis
      in flies or mammals. We used several approaches to remove maternal and zygotic
      Ena function, allowing us to address this question. We found that inactivating
      Ena does not disrupt cell adhesion or epithelial organization, suggesting its
      role in these processes is cell type-specific. However, Ena plays an important
      role in many morphogenetic events, including germband retraction, segmental
      groove retraction and head involution, whereas it is dispensable for other
      morphogenetic movements. We focused on dorsal closure, analyzing mechanisms by
      which Ena acts. Ena modulates filopodial number and length, thus influencing the
      speed of epithelial zippering and the ability of cells to match with correct
      neighbors. We also explored filopodial regulation in cultured Drosophila cells
      and embryos. These data provide new insights into developmental and mechanistic
      roles of this important actin regulator.

PMID- 17507405
TI  - Bmp and Fgf signaling are essential for liver specification in zebrafish.
AB  - Based on data from in vitro tissue explant and ex vivo cell/bead implantation
      experiments, Bmp and Fgf signaling have been proposed to regulate hepatic
      specification. However, genetic evidence for this hypothesis has been lacking.
      Here, we provide in vivo genetic evidence that Bmp and Fgf signaling are
      essential for hepatic specification. We utilized transgenic zebrafish that
      overexpress dominant-negative forms of Bmp or Fgf receptors following heat-shock
      induction. These transgenes allow one to bypass the early embryonic requirements
      for Bmp and Fgf signaling, and also to completely block Bmp or Fgf signaling. We
      found that the expression of hhex and prox1, the earliest liver markers in
      zebrafish, was severely reduced in the liver region when Bmp or Fgf signaling was
      blocked just before hepatic specification. However, hhex and prox1 expression in
      adjacent endodermal and mesodermal tissues appeared unaffected by these
      manipulations. Additional genetic studies indicate that the endoderm maintains
      competence for Bmp-mediated hepatogenesis over an extended window of embryonic
      development. Altogether, these data provide the first genetic evidence that Bmp
      and Fgf signaling are essential for hepatic specification, and suggest that
      endodermal cells remain competent to differentiate into hepatocytes for longer
      than anticipated.

PMID- 17507406
TI  - Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick
      embryo.
AB  - The TGF-beta-related molecule Nodal plays an essential and conserved role in left
      right patterning of the vertebrate embryo. Previous reports have shown that the
      zebrafish and mouse Cerberus-related proteins Charon and Cerberus-like-2 (Cerl
      2), respectively, act in the node region to prevent the Nodal signal from
      crossing to the right side, whereas chick Cerberus (cCer) has an unclear function
      in the left-side mesoderm. In this study, we investigate the transcriptional
      regulation and function of cCer in left-right development. By analyzing the
      enhancer activity of cCer 5' genomic sequences in electroporated chick embryos,
      we identified a cCer left-side enhancer that contains two FoxH1 and one SMAD
      binding site. We show that these Nodal-responsive elements are necessary and
      sufficient for the activation of transcription in the left-side mesoderm. In
      transgenic mouse embryos, cCer regulatory sequences behave as in chick embryos,
      suggesting that the cis-regulatory sequences of Cerberus-related genes have
      diverged during vertebrate evolution. Moreover, our findings from cCer
      overexpression and knockdown experiments indicate that cCer is a negative
      feedback regulator of Nodal asymmetric signaling. We propose that cCer and mouse
      Cerl-2 have evolved distinct regulatory mechanisms but retained a conserved
      function in left-right development, which is to restrict Nodal activity to the
      left side of the embryo.

PMID- 17507407
TI  - Drosophila Nemo antagonizes BMP signaling by phosphorylation of Mad and
      inhibition of its nuclear accumulation.
AB  - Drosophila Nemo is the founding member of the Nemo-like kinase (Nlk) family of
      serine/threonine protein kinases that are involved in several Wnt signal
      transduction pathways. Here we report a novel function for Nemo in the inhibition
      of bone morphogenetic protein (BMP) signaling. Genetic interaction studies
      demonstrate that nemo can antagonize BMP signaling and can inhibit the expression
      of BMP target genes during wing development. Nemo can bind to and phosphorylate
      the BMP effector Mad. In cell culture, phosphorylation by Nemo blocks the nuclear
      accumulation of Mad by promoting export of Mad from the nucleus in a kinase
      dependent manner. This is the first example of the inhibition of Drosophila BMP
      signaling by a MAPK and represents a novel mechanism of Smad inhibition through
      the phosphorylation of a conserved serine residue within the MH1 domain of Mad.

PMID- 17507408
TI  - Integration of cytokinin and gibberellin signalling by Arabidopsis transcription
      factors GIS, ZFP8 and GIS2 in the regulation of epidermal cell fate.
AB  - The effective integration of hormone signals is essential to normal plant growth
      and development. Gibberellins (GA) and cytokinins act antagonistically in leaf
      formation and meristem maintenance and GA counteract some of the effects of
      cytokinins on epidermal differentiation. However, both can stimulate the
      initiation of defensive epidermal structures called trichomes. To understand how
      their relative influence on epidermal cell fate is modulated, we investigated the
      molecular mechanisms through which they regulate trichome initiation in
      Arabidopsis. The control by cytokinins of trichome production requires two genes
      expressed in late inflorescence organs, ZFP8 and GIS2, which encode C2H2
      transcription factors related to GLABROUS INFLORESCENCE STEMS (GIS). Cytokinin
      inducible GIS2 plays a prominent role in the cytokinin response, in which it acts
      downstream of SPINDLY and upstream of GLABROUS1. In addition, GIS2 and ZFP8
      mediate, like GIS, the regulation of trichome initiation by gibberellins. By
      contrast, GIS does not play a significant role in the cytokinin response.
      Collectively, GIS, ZFP8 and GIS2, which encode proteins that are largely
      equivalent in function, play partially redundant and essential roles in
      inflorescence trichome initiation and in its regulation by GA and cytokinins.
      These roles are consistent with their pattern of expression and with the regional
      influence of GA and cytokinins on epidermal differentiation. Our findings show
      that functional specialization within a transcription factor gene family can
      facilitate the integration of different developmental cues in the regulation of
      plant cell differentiation.

PMID- 17507409
TI  - A clonal analysis of neural progenitors during axolotl spinal cord regeneration
      reveals evidence for both spatially restricted and multipotent progenitors.
AB  - Complete regeneration of the spinal cord occurs after tail regeneration in
      urodele amphibians such as the axolotl. Little is known about how neural
      progenitor cells are recruited from the mature tail, how they populate the
      regenerating spinal cord, and whether the neural progenitor cells are
      multipotent. To address these issues we used three types of cell fate mapping. By
      grafting green fluorescent protein-positive (GFP(+)) spinal cord we show that a
      500 microm region adjacent to the amputation plane generates the neural
      progenitors for regeneration. We further tracked single nuclear-GFP-labeled cells
      as they proliferated during regeneration, observing their spatial distribution,
      and ultimately their expression of the progenitor markers PAX7 and PAX6. Most
      progenitors generate descendents that expand along the anterior/posterior (A/P)
      axis, but remain close to the dorsal/ventral (D/V) location of the parent. A
      minority of clones spanned multiple D/V domains, taking up differing molecular
      identities, indicating that cells can execute multipotency in vivo. In parallel
      experiments, bulk labeling of dorsally or ventrally restricted progenitor cells
      revealed that ventral cells at the distal end of the regenerating spinal cord
      switch to dorsal cell fates. Analysis of PAX7 and PAX6 expression along the
      regenerating spinal cord indicated that these markers are expressed in dorsal and
      lateral domains all along the spinal cord except at the distal terminus. These
      results suggest that neural progenitor identity is destabilized or altered in the
      terminal vesicle region, from which clear migration of cells into the surrounding
      blastema is also observed.

PMID- 17507410
TI  - Region-specific requirement for cholesterol modification of sonic hedgehog in
      patterning the telencephalon and spinal cord.
AB  - Sonic hedgehog (Shh) secreted from the axial signaling centers of the notochord
      and prechordal plate functions as a morphogen in dorsoventral patterning of the
      neural tube. Active Shh is uniquely cholesterol-modified and the hydrophobic
      nature of cholesterol suggests that it might regulate Shh spreading in the neural
      tube. Here, we examined the capacity of Shh lacking the cholesterol moiety (ShhN)
      to pattern different cell types in the telencephalon and spinal cord. In mice
      expressing ShhN, we detected low-level ShhN in the prechordal plate and
      notochord, consistent with the notion that ShhN can rapidly spread from its site
      of synthesis. Surprisingly, we found that low-level ShhN can elicit the
      generation of a full spectrum of ventral cell types in the spinal cord, whereas
      ventral neuronal specification and ganglionic eminence development in the Shh(N/
      ) telencephalon were severely impaired, suggesting that telencephalic patterning
      is more sensitive to alterations in local Shh concentration and spreading. In
      agreement, we observed induction of Shh pathway activity and expression of
      ventral markers at ectopic sites in the dorsal telencephalon indicative of long
      range ShhN activity. Our findings indicate an essential role for the cholesterol
      moiety in restricting Shh dilution and deregulated spread for patterning the
      telencephalon. We propose that the differential effect of ShhN in patterning the
      spinal cord versus telencephalon may be attributed to regional differences in the
      maintenance of Shh expression in the ventral neuroepithelium and differences in
      dorsal tissue responsiveness to deregulated Shh spreading behavior.

PMID- 17507411
TI  - Dissection of the target specificity of the RNA-binding protein HOW reveals dpp
      mRNA as a novel HOW target.
AB  - Regulation of RNA metabolism plays a major role in controlling gene expression
      during developmental processes. The Drosophila RNA-binding protein Held out wing
      (HOW), regulates an array of developmental processes in embryonic and adult
      growth. We have characterized the primary sequence and secondary structural
      requirements for the HOW response element (HRE), and show that this site is
      necessary and sufficient for HOW binding. Based on this analysis, we have
      identified the Drosophila TGFbeta homolog, dpp, as a novel direct target for HOW
      negative regulation in the wing imaginal disc. The binding of the repressor
      isoform HOW(L) to the dpp 3' untranslated region (UTR) leads to a reduction of
      GFP-dpp3'UTR reporter levels in S-2 cells, in an HRE site-dependent manner.
      Moreover, co-expression of HOW(L) in the wing imaginal disc with a dpp-GFP fusion
      construct led to a reduction in DPP-GFP levels in a dpp-3'UTR-dependent manner.
      Conversely, a reduction of the endogenous levels of HOW by targeted expression of
      HOW-specific double-stranded RNA led to a corresponding elevation in dpp mRNA
      level in the wing imaginal disc. Thus, by characterizing the RNA sequences that
      bind HOW, we demonstrate a novel aspect of regulation, at the mRNA level, of
      Drosophila DPP.

PMID- 17507412
TI  - Regulation of ventral midbrain patterning by Hedgehog signaling.
AB  - In the developing ventral midbrain, the signaling molecule sonic hedgehog (SHH)
      is sufficient to specify a striped pattern of cell fates (midbrain arcs). Here,
      we asked whether and precisely how hedgehog (HH) signaling might be necessary for
      ventral midbrain patterning. By blocking HH signaling by in ovo misexpression of
      Ptc1(Delta)(loop2), we show that HH signaling is necessary and can act directly
      at a distance to specify midbrain cell fates. Ventral midbrain progenitors
      extinguish their dependence upon HH in a spatiotemporally complex manner,
      completing cell-fate specification at the periphery by Hamburger and Hamilton
      stage 13. Thus, patterning at the lateral periphery of the ventral midbrain is
      accomplished early, when the midbrain is small and the HH signal needs to travel
      relatively short distances (approximately 30 cell diameters). Interestingly,
      single-cell injections demonstrate that patterning in the midbrain occurs within
      the context of cortex-like radial columns of cells that can share HH blockade and
      are cytoplasmically connected by gap junctions. HH blockade results in increased
      cell scatter, disrupting the spatial coherence of the midbrain arc pattern.
      Finally, HH signaling is required for the integrity and the signaling properties
      of the boundaries of the midbrain (e.g. the midbrain-hindbrain boundary, the
      dorsoventral boundary), its perturbations resulting in abnormal cell mixing
      across 'leaky' borders.

PMID- 17507413
TI  - Wnt signals provide a timing mechanism for the FGF-retinoid differentiation
      switch during vertebrate body axis extension.
AB  - Differentiation onset in the vertebrate body axis is controlled by a conserved
      switch from fibroblast growth factor (FGF) to retinoid signalling, which is also
      apparent in the extending limb and aberrant in many cancer cell lines. FGF
      protects tail-end stem zone cells from precocious differentiation by inhibiting
      retinoid synthesis, whereas later-produced retinoic acid (RA) attenuates FGF
      signalling and drives differentiation. The timing of RA production is therefore
      crucial for the preservation of stem zone cells and the continued extension of
      the body axis. Here we show that canonical Wnt signalling mediates the transition
      from FGF to retinoid signalling in the newly generated chick body axis. FGF
      promotes Wnt8c expression, which persists in the neuroepithelium as FGF
      signalling declines. Wnt signals then act here to repress neuronal
      differentiation. Furthermore, although FGF inhibition of neuronal differentiation
      involves repression of the RA-responsive gene, retinoic acid receptor beta
      (RARbeta), Wnt signals are weaker repressors of neuron production and do not
      interfere with RA signal transduction. Strikingly, as FGF signals decline in the
      extending axis, Wnt signals now elicit RA synthesis in neighbouring presomitic
      mesoderm. This study identifies a directional signalling relay that leads from
      FGF to retinoid signalling and demonstrates that Wnt signals serve, as cells
      leave the stem zone, to permit and promote RA activity, providing a mechanism to
      control the timing of the FGF-RA differentiation switch.

PMID- 17507414
TI  - Ena/VASP function in retinal axons is required for terminal arborization but not
      pathway navigation.
AB  - The Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family of proteins
      is required for filopodia formation in growth cones and plays a crucial role in
      guidance cue-induced remodeling of the actin cytoskeleton. In vivo studies with
      pharmacological inhibitors of actin polymerization have previously provided
      evidence for the view that filopodia are needed for growth cone navigation in the
      developing visual pathway. Here we have re-examined this issue using an
      alternative strategy to generate growth cones without filopodia in vivo by
      artificially targeting Xena/XVASP (Xenopus homologs of Ena/VASP) proteins to
      mitochondria in retinal ganglion cells (RGCs). We used the specific binding of
      the EVH1 domain of the Ena/VASP family of proteins with the ligand motif FP4 to
      sequester the protein at the mitochondria surface. RGCs with reduced function of
      Xena/XVASP proteins extended fewer axons out of the eye and possessed dynamic
      lamellipodial growth cones missing filopodia that advanced slowly in the optic
      tract. Surprisingly, despite lacking filopodia, the axons navigated along the
      optic pathway without obvious guidance errors, indicating that the Xena/XVASP
      family of proteins and filopodial protrusions are non-essential for pathfinding
      in retinal axons. However, depletion of Xena/XVASP proteins severely impaired the
      ability of growth cones to form branches within the optic tectum, suggesting that
      this protein family, and probably filopodia, plays a key role in establishing
      terminal arborizations.

PMID- 17507416
TI  - Conditional Kif3a ablation causes abnormal hedgehog signaling topography, growth
      plate dysfunction, and excessive bone and cartilage formation during mouse
      skeletogenesis.
AB  - The motor protein Kif3a and primary cilia regulate important developmental
      processes, but their roles in skeletogenesis remain ill-defined. Here we created
      mice deficient in Kif3a in cartilage and focused on the cranial base and
      synchondroses. Kif3a deficiency caused cranial base growth retardation and
      dysmorphogenesis, which were evident in neonatal animals by anatomical and micro
      computed tomography (microCT) inspection. Kif3a deficiency also changed
      synchondrosis growth plate organization and function, and the severity of these
      changes increased over time. By postnatal day (P)7, mutant growth plates lacked
      typical zones of chondrocyte proliferation and hypertrophy, and were instead
      composed of chondrocytes with an unusual phenotype characterized by strong
      collagen II (Col2a1) gene expression but barely detectable expression of Indian
      hedgehog (Ihh), collagen X (Col10a1), Vegf (Vegfa), MMP-13 (Mmp13) and osterix
      (Sp7). Concurrently, unexpected developmental events occurred in perichondrial
      tissues, including excessive intramembranous ossification all along the
      perichondrial border and the formation of ectopic cartilage masses. Looking for
      possible culprits for these latter processes, we analyzed hedgehog signalling
      topography and intensity by monitoring the expression of the hedgehog effectors
      Patched 1 and Gli1, and of the hedgehog-binding cell-surface component syndecan
      3. Compared with controls, hedgehog signaling was quite feeble within mutant
      growth plates as early as P0, but was actually higher and was widespread all
      along mutant perichondrial tissues. Lastly, we studied postnatal mice deficient
      in Ihh in cartilage; their cranial base defects only minimally resembled those in
      Kif3a-deficient mice. In summary, Kif3a and primary cilia make unique
      contributions to cranial base development and synchondrosis growth plate
      function. Their deficiency causes abnormal topography of hedgehog signaling,
      growth plate dysfunction, and un-physiologic responses and processes in
      perichondrial tissues, including ectopic cartilage formation and excessive
      intramembranous ossification.

PMID- 17507415
TI  - Repression of the hindbrain developmental program by Cdx factors is required for
      the specification of the vertebrate spinal cord.
AB  - The spinal cord is a unique vertebrate feature that originates, together with the
      hindbrain, from the caudal neural plate. Whereas the hindbrain subdivides into
      rhombomeres, the spinal cord remains unsegmented. We have identified Cdx
      transcription factors as key determinants of the spinal cord region in zebrafish.
      Loss of Cdx1a and Cdx4 functions causes posterior expansion of the hindbrain at
      the expense of the unsegmented spinal cord. By contrast, cdx4 overexpression in
      the hindbrain impairs rhombomere segmentation and patterning and induces the
      expression of spinal cord-specific genes. Using cell transplantation, we
      demonstrate that Cdx factors function directly within the neural ectoderm to
      specify spinal cord. Overexpression of 5' Hox genes fails to rescue hindbrain and
      spinal cord defects associated with cdx1a/cdx4 loss-of-function, suggesting a Hox
      independent mechanism of spinal cord specification. In the absence of Cdx
      function, the caudal neural plate retains hindbrain characteristics and remains
      responsive to surrounding signals, particularly retinoic acid, in a manner
      similar to the native hindbrain. We propose that by preventing the posterior-most
      region of the neural plate from following a hindbrain developmental program, Cdx
      factors help determine the size of the prospective hindbrain and spinal cord
      territories.

PMID- 17507417
TI  - Conditional ablation of GFRalpha1 in postmigratory enteric neurons triggers
      unconventional neuronal death in the colon and causes a Hirschsprung's disease
      phenotype.
AB  - The regulation of neuronal survival and death by neurotrophic factors plays a
      central role in the sculpting of the nervous system, but the identity of survival
      signals for developing enteric neurons remains obscure. We demonstrate here that
      conditional ablation of GFRalpha1, the high affinity receptor for GDNF, in mice
      during late gestation induces rapid and widespread neuronal death in the colon,
      leading to colon aganglionosis reminiscent of Hirschsprung's disease. Enteric
      neuron death induced by GFRalpha1 inactivation is not associated with the
      activation of common cell death executors, caspase-3 or -7, and lacks the
      morphological hallmarks of apoptosis, such as chromatin compaction and
      mitochondrial pathology. Consistent with these in vivo observations, neither
      caspase inhibition nor Bax deficiency blocks death of colon-derived enteric
      neurons induced by GDNF deprivation. This study reveals an essential role for
      GFRalpha1 in the survival of enteric neurons and suggests that caspase
      independent death can be triggered by abolition of neurotrophic signals.

PMID- 17507418
TI  - The Drosophila Lkb1 kinase is required for spindle formation and asymmetric
      neuroblast division.
AB  - We have isolated lethal mutations in the Drosophila lkb1 gene (dlkb1), the
      homolog of C. elegans par-4 and human LKB1 (STK11), which is mutated in Peutz
      Jeghers syndrome. We show that these mutations disrupt spindle formation,
      resulting in frequent polyploid cells in larval brains. In addition, dlkb1
      mutations affect asymmetric division of larval neuroblasts (NBs); they suppress
      unequal cytokinesis, abrogate proper localization of Bazooka, Par-6, DaPKC and
      Miranda, but affect neither Pins/Galphai localization nor spindle rotation. Most
      aspects of the dlkb1 phenotype are exacerbated in dlkb1 pins double mutants,
      which exhibit more severe defects than those observed in either single mutant.
      This suggests that Dlkb1 and Pins act in partially redundant pathways to control
      the asymmetry of NB divisions. Our results also indicate that Dlkb1 and Pins
      function in parallel pathways controlling the stability of spindle microtubules.
      The finding that Dlkb1 mediates both the geometry of stem cell division and
      chromosome segregation provides novel insight into the mechanisms underlying
      tumor formation in Peutz-Jeghers patients.

PMID- 17507420
TI  - Clinical implications of multiple drug resistance efflux pumps of pathogenic
      bacteria.
AB  - Resistance of microorganisms to many classes of antibiotics and other drugs is a
      major problem throughout the world. This antimicrobial resistance can be mediated
      by various mechanisms such as enzymatic inactivation of the drug, alteration of
      the target and decreased intracellular concentration of the antimicrobial. The
      latter mechanism is mediated by either decreased influx or increased efflux or a
      combination of both. Recently, efflux has become increasingly recognized as a
      major component of resistance. Some efflux pumps selectively extrude specific
      antibiotics such as macrolides, lincosamides and/or streptogramins and
      tetracyclines, whereas others, referred to as multiple drug resistance pumps,
      expel a variety of structurally diverse anti-infectives with different modes of
      action. This phenomenon, whereby a single transporter is able to recognize and
      transport multiple antimicrobials with no common structural homology, was first
      described in the late 1980s in higher eukaryotes where P-glycoprotein was found
      to play a role in resistance to anti-cancer chemotherapeutic agents. Later, it
      became apparent that efflux systems were also present in microorganisms. Efflux
      pump inhibitors offer considerable promise as therapeutic agents, as they should
      restore the activity of standard antibiotics.

PMID- 17507419
TI  - Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one
      subtype due to mutations in the telomerase-associated protein NOP10.
AB  - Dyskeratosis congenita (DC) is characterized by multiple features including
      mucocutaneous abnormalities, bone marrow failure and an increased predisposition
      to cancer. It exhibits marked clinical and genetic heterogeneity. DKC1 encoding
      dyskerin, a component of H/ACA small nucleolar ribonucleoprotein (snoRNP)
      particles is mutated in X-linked recessive DC. Telomerase RNA component (TERC),
      the RNA component and TERT the enzymatic component of telomerase, are mutated in
      autosomal dominant DC, suggesting that DC is primarily a disease of defective
      telomere maintenance. The gene(s) involved in autosomal recessive DC remains
      elusive. This paper describes studies aimed at defining the genetic basis of AR
      DC. Homozygosity mapping in 16 consanguineous families with 25 affected
      individuals demonstrates that there is no single genetic locus for AR-DC.
      However, we show that NOP10, a component of H/ACA snoRNP complexes including
      telomerase is mutated in a large consanguineous family with classical DC.
      Affected homozygous individuals have significant telomere shortening and reduced
      TERC levels. While a reduction of TERC levels is not a universal feature of DC,
      it can be brought about through a reduction of NOP10 transcripts, as demonstrated
      by siRNA interference studies. A similar reduction in TERC levels is also seen
      when the mutant NOP10 is expressed in HeLa cells. These findings identify the
      genetic basis of one subtype of AR-DC being due to the first documented mutations
      in NOP10. This further strengthens the model that defective telomere maintenance
      is the primary pathology in DC and substantiates the evidence in humans for the
      involvement of NOP10 in the telomerase complex and telomere maintenance.

PMID- 17507421
TI  - Accuracy of health examination results self-reported by Japanese participants.
AB  - BACKGROUND: We evaluated the accuracy of self-reported health examination results
      by participants regarding their most recent public health examination by
      comparing their answers to the medical records in order to determine individual
      factors related to self-reporting accuracy. METHODS: The study was conducted at
      Settsu City in Osaka prefecture, Japan, in 1998 with 3570 participants who
      underwent general health examinations conducted by the municipal government. All
      participants were interviewed regarding their lifestyle as well as health
      guidance given at their previous examination, after which their answers were
      compared with the data from their medical records. The adjusted odds ratio (OR)
      for providing accurate self-reporting was calculated by multivariate logistic
      analyses. RESULTS: The frequency of accurate self-reporting was 49.4% and the
      overall Kappa value was 0.34. The OR for accurate self-reporting was lowest for
      those who have a poor lifestyle compared with those who had a good lifestyle.
      CONCLUSION: The accuracy of self-reported health examination results was poor. We
      concluded that information based on self-reported results of a health examination
      must be considered carefully. Further, lifestyle was found to be associated with
      the ability to accurately recall. Thus, methods for providing guidance to
      individuals with a poor life style must be carefully examined.

PMID- 17507423
TI  - Approach for guideline development.

PMID- 17507422
TI  - Community beliefs about childhood obesity: its causes, consequences and potential
      solutions.
AB  - BACKGROUND: The objective of this study was to explore community beliefs about
      the causes, consequences and potential solutions of childhood obesity. METHODS: A
      convenience sample of 434 adults (41.2 +/- 13.3 years; 61% parents) in New South
      Wales, Australia, was surveyed using a newly developed childhood obesity scale.
      RESULTS: Five causal (emotional eating; eating habits and food knowledge;
      environmental dysfunction; abundance of contemporary lifestyle; cost of
      contemporary lifestyle), four consequences (known consequences of obesity;
      behavioural consequences; social consequences; less-known physical consequences)
      and three potential solutions factors (parental actions; professional assistance;
      limiting behaviours) were identified. Parents did not differ from non-parents
      across the 12 factors nor were there any differences based on the level of
      education. There were, however, gender differences across two causal factors
      (emotional eating and abundance of contemporary lifestyle) and two consequences
      factors (behavioural consequences and social consequences), with females
      endorsing all four factors more strongly than males. CONCLUSIONS: The results of
      this study suggest that this sample was aware of the complex nature of childhood
      obesity in terms of its causes, consequences and a range of potential solutions,
      but they endorsed more family rather than community-based interventions.

PMID- 17507425
TI  - EBPG guideline on haemodynamic instability.

PMID- 17507426
TI  - EBPG guideline on nutrition.

PMID- 17507427
TI  - EBPG guideline on dialysis strategies.

PMID- 17507428
TI  - EBPG on Vascular Access.

PMID- 17507429
TI  - PKCdelta mediates anti-proliferative, pro-apoptic effects of testosterone on
      coronary smooth muscle.
AB  - Sex hormone status has emerged as an important modulator of coronary physiology
      and cardiovascular disease risk in both males and females. Our previous studies
      have demonstrated that testosterone increases protein kinase C (PKC) delta
      expression and activity in coronary smooth muscle (CSMC). Because PKCdelta has
      been implicated in regulation of proliferation and apoptosis in other cell types,
      we sought to determine if testosterone modulates CSMC proliferation and/or
      apoptosis through PKCdelta. Porcine CSMC cultures (passages 2-6) from castrated
      males were treated with testosterone for 24 h. Testosterone (20 and 100 nM)
      decreased [(3)H]thymidine incorporation in proliferating CSMC to 59 +/- 5.3 and
      33.1 +/- 4.5% of control. Flow cytometric analysis demonstrated that testosterone
      induced G(1) arrest in CSMC with a concomitant reduction in the S phase cells.
      Testosterone reduced protein levels of cyclins D(1) and E and phosphorylation of
      retinoblastoma protein while elevating levels of p21(cip1) and p27(kip1). There
      were no significant differences in the levels of cyclins D(3), CDK2, CDK4, or
      CDK6. Testosterone significantly reduced kinase activity of CDK2 and -6, but not
      CDK4, -7, or -1. PKCdelta small interfering RNA (siRNA) prevented testosterone
      mediated G(1) arrest, p21(cip1) upregulation, and cyclin D(1) and E
      downregulation. Furthermore, testosterone increased CSMC apoptosis in a dose
      dependent manner, which was blocked by either PKCdelta siRNA or caspase 3
      inhibition. These findings demonstrate that the anti-proliferative, pro-apoptotic
      effects of testosterone on CSMCs are substantially mediated by PKCdelta.

PMID- 17507430
TI  - Integration of signal pathways for stretch-dependent growth and differentiation
      in vascular smooth muscle.
AB  - The vascular smooth muscle phenotype is regulated by environmental factors, such
      as mechanical forces, that exert effects on signaling to differentiation and
      growth. We used the mouse portal vein in organ culture to investigate stretch
      dependent activation of Akt, ERK, and focal adhesion kinase (FAK), which have
      been suggested to be involved in the regulation of stretch-dependent protein
      synthesis. The role of actin polymerization in these signaling events was
      examined using the actin-stabilizing agent jasplakinolide. Stretch caused a
      biphasic activation of FAK at 5-15 min and 24-72 h, which may reflect first a
      direct phosphorylation of preexisting focal adhesions followed by a rearrangement
      of focal adhesions to accommodate for the increased mechanical load.
      Phosphorylation of ERK was increased by acute stretch but then decreased, and Akt
      did not have a distinct peak in stretch-induced phosphorylation. Inhibition of
      ERK, phosphatidylinositol 3-kinase, or mammalian target of rapamycin reduced
      global but not contractile protein synthesis with maintained stretch sensitivity.
      Stabilization of actin filaments with jasplakinolide, in unstretched portal
      veins, resulted in increased ERK phosphorylation and global protein synthesis as
      well as the synthesis of contractile proteins. In contrast, stretch during
      culture with jasplakinolide did not affect FAK phosphorylation or contractility.
      Therefore, remodeling of smooth muscle cells to adapt to stretch requires a
      dynamic cytoskeleton.

PMID- 17507431
TI  - MMPs contribute to TNF-alpha-induced alteration of the blood-cerebrospinal fluid
      barrier in vitro.
AB  - The epithelial cells of the choroid plexus separate the central nervous system
      from the blood forming the blood-cerebrospinal fluid (CSF) barrier. The choroid
      plexus is the main source of CSF, whose composition is markedly changed during
      pathological disorders, for example regarding matrix metalloproteases (MMPs) and
      tissue inhibitors of matrix metalloproteases (TIMPs). In the present study, we
      analyzed the impact of the proinflammatory cytokine tumor necrosis factor-alpha
      (TNF-alpha) on the blood-CSF barrier using an in vitro model based on porcine
      choroid plexus epithelial cells (PCPEC). TNF-alpha evoked distinct inflammatory
      processes as shown by mRNA upregulation of intercellular adhesion molecule-1 and
      vascular cell adhesion molecule-1. The cytokine caused a drastic decrease in
      transepithelial electrical resistance within several hours representing an
      enhanced permeability of PCPEC monolayers. In addition, the distribution of tight
      junction proteins was altered. Moreover, MMP activity in PCPEC supernatants was
      significantly increased by TNF-alpha, presumably due to a diminished expression
      of TIMP-3 that was similarly observed. MMP-2, -3, and -9 as well as TIMP-1 and -2
      were also analyzed and found to be differentially regulated by the cytokine. The
      TNF-alpha-induced breakdown of the blood-CSF barrier could partially be blocked
      by the MMP inhibitor GM-6001. Our results show a contribution of MMPs to the
      inflammatory breakdown of the blood-CSF barrier in vitro. Thus TNF-alpha may
      mediate the binding of leukocytes to cellular adhesion molecules and the
      transmigration across the blood-CSF barrier.

PMID- 17507432
TI  - Different kinases regulate activation of voltage-dependent calcium channels by
      depolarization in GH3 cells.
AB  - The L-type Ca(2+) channel is the primary voltage-dependent Ca(2+)-influx pathway
      in many excitable and secretory cells, and direct phosphorylation by different
      kinases is one of the mechanisms involved in the regulation of its activity. The
      aim of this study was to evaluate the participation of Ser/Thr kinases and
      tyrosine kinases (TKs) in depolarization-induced Ca(2+) influx in the endocrine
      somatomammotrope cell line GH3. Intracellular Ca(2+) concentration ([Ca(2+)](i))
      was measured using a spectrofluorometric method with fura 2-AM, and 12.5 mM KCl
      (K(+)) was used as a depolarization stimulus. K(+) induced an abrupt spike (peak)
      in [Ca(2+)](i) that was abolished in the presence of nifedipine, showing that
      K(+) enhances [Ca(2+)](i), preferably activating L-type Ca(2+) channels. H89, a
      selective PKA inhibitor, significantly reduced depolarization-induced Ca(2+)
      mobilization in a concentration-related manner when it was applied before or
      after K(+), and okadaic acid, an inhibitor of Ser/Thr phosphatases, which has
      been shown to regulate PKA-stimulated L-type Ca(2+) channels, increased K(+)
      induced Ca(2+) entry. When PKC was activated by PMA, the K(+)-evoked peak in
      [Ca(2+)](i), as well as the plateau phase, was significantly reduced, and
      chelerythrine (a PKC inhibitor) potentiated the K(+)-induced increase in
      [Ca(2+)](i), indicating an inhibitory role of PKC in voltage-dependent Ca(2+)
      channel (VDCC) activity. Genistein, a TK inhibitor, reduced the K(+)-evoked
      increase in [Ca(2+)](i), but, unexpectedly, the tyrosine phosphatase inhibitor
      orthovanadate reduced not only basal Ca(2+) levels but, also, Ca(2+) influx
      during the plateau phase. Both results suggest that different TKs may act
      differentially on VDCC activation. Activation of receptor TKs with epidermal
      growth factor (EGF) or vascular endothelial growth factor potentiated K(+)
      induced Ca(2+) influx, and AG-1478 (an EGF receptor inhibitor) decreased it.
      However, inhibition of the non-receptor TK pp60 c-Src enhanced K(+)-induced
      Ca(2+) influx. The present study strongly demonstrates that a complex equilibrium
      among different kinases and phosphatases regulates VDCC activity in the pituitary
      cell line GH3: PKA and receptor TKs, such as vascular endothelial growth factor
      receptor and EGF receptor, enhance depolarization-induced Ca(2+) influx, whereas
      PKC and c-Src have an inhibitory effect. These kinases modulate membrane
      depolarization and may therefore participate in the regulation of a plethora of
      intracellular processes, such as hormone secretion, gene expression, protein
      synthesis, and cell proliferation, in pituitary cells.

PMID- 17507433
TI  - The inexhaustible mouse nose. Focus on "olfactory epithelia exhibit progressive
      functional and morphological defects in CF mice".

PMID- 17507434
TI  - Maternal undernutrition inhibits angiogenesis in the offspring: a potential
      mechanism of programmed hypertension.
AB  - The underlying etiology of many chronic diseases such as hypertension and
      diabetes has been traced to the in utero environment. Our interest has focused on
      determining the mechanism of programmed hypertension. In our rodent model of 50%
      maternal food restriction (MFR) from day 10 of gestation to term, the offspring
      develop hypertension as adults. We hypothesized that maternal undernutrition
      inhibits angiogenesis such that the neonate is endowed with fewer microvessels,
      increasing their susceptibility to develop hypertension as adults. We found
      significantly reduced number of mesenteric branching and renal medullary
      microvessels in the 1-day-old MFR newborns. Endothelial cells from MFR offspring
      generated shorter neovessels in culture compared with controls. The inhibition of
      angiogenesis was associated with a significant decrease in VEGF protein
      expression in mesenteric microvessels and aortas in 1-day-old offspring. However,
      in adulthood there was a marked increase in VEGF expression in both vessel types.
      The expression of endothelial nitric oxide synthase protein was also found to be
      increased in both renal and mesenteric microvessels and in aortas in the 1-day
      old MFR offspring. These results suggest that MFR results in inhibition of VEGF
      expression in microvascular and aortic endothelial cells early in life, resulting
      in decreased angiogenesis and increased peripheral vascular resistance, both of
      which may contribute to offspring hypertension.

PMID- 17507435
TI  - Placental HIF-1 alpha, HIF-2 alpha, membrane and soluble VEGF receptor-1 proteins
      are not increased in normotensive pregnancies complicated by late-onset
      intrauterine growth restriction.
AB  - Inadequate trophoblast invasion and spiral artery remodeling leading to poor
      placental perfusion are believed to underlie the pregnancy pathologies
      preeclampsia (PE) and intrauterine growth restriction (IUGR). The main objective
      of this study was to investigate hypoxia-inducible transcription factor-alpha
      (HIF-alpha) and downstream genes (VEGF receptor-1) Flt-1 and soluble fms-like
      tyrosine kinase 1 (sFlt-1) proteins in IUGR placentas. Placentas from normal
      pregnant (NP; n = 18), PE (n = 18), and IUGR (n = 10) patients were investigated.
      Normotensive patients with IUGR delivered babies at >or= 37 wk of gestation with
      birth weights of <10% and asymmetrical growth. HIF-1 alpha, -2 alpha, Flt-1, and
      sFlt-1 protein, and mRNA were assessed by Western and Northern blot analyses,
      respectively. The results are expressed as ratios of the densitometric values for
      each pair of pathologic and normal placentas, a ratio of 1.0 indicating no
      difference. Comparable to our earlier studies, the PE/NP ratios for HIF-1 alpha, 
      2 alpha, and Flt proteins were significantly increased by 50-100% (all P < 0.01
      vs. 1.0). Unexpectedly, the IUGR/NP ratios for HIF-1 alpha and -2 alpha proteins
      were 1.03 +/- 0.07 and 0.96 +/- 0.16, respectively, and for Flt and sFlt were
      1.14 +/- 0.15 and 0.95 +/- 0.12, respectively (all P = not significant vs. 1.0).
      Northern blot analysis revealed comparable levels of HIF-alpha mRNA in abnormal
      and normal placentas. In contrast to PE, HIF-alpha proteins and regulated genes
      are not increased in placentas from normotensive pregnant women delivering small,
      asymmetrically grown babies >or= 37 wk of gestation. The absence of an increase
      in HIF-alpha protein is not due to insufficient HIF-alpha mRNA for protein
      synthesis. Thus, the placentas from women with PE and late IUGR are fundamentally
      different at the molecular level.

PMID- 17507436
TI  - Exercise training improves myocardial tolerance to ischemia in male but not in
      female rats.
AB  - Acute exercise increases myocardial tolerance to ischemia-reperfusion (I-R)
      injury in male but not in female rat hearts, possibly due to a decreased heat
      shock protein 70 (Hsp70) response in the female hearts. This study examined
      whether repetitive exercise training would increase Hsp70 and myocardial
      tolerance to I-R injury in female rat hearts. Adaptations in myocardial manganese
      superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) were
      also assessed. Ten-week old male (M) and female (F) Sprague-Dawley rats (n = 40
      total) exercise-trained for 14 wk; the last 8 wk consisted of running 1 h at 30
      m/min (2% incline), 5 days/wk. Following training, left ventricle mechanical
      function (LVMF) was monitored for 30 min of reperfusion following 30 min of
      global ischemia (Langendorff procedure). Myocardial Hsp70 content was not
      different in M and F control groups, while increases were observed in both
      trained groups (M greater than F; P < 0.05). Although MnSOD content did not
      differ between groups, endothelial nitric oxide synthase (eNOS) levels were
      decreased in F, with no change in M, following training (P < 0.05). Hearts from
      control F demonstrated a greater recuperation of all indices of LVMF following I
      R compared with control M hearts (P < 0.05). Hearts of trained M exhibited
      improved recovery of LVMF (left ventricular diastolic pressure, left ventricular
      end-diastolic pressure, +dP/dt, -dP/dt) during reperfusion compared with control
      M hearts (P < 0.05). In contrast, hearts of trained F did not show any change in
      recovery from I-R. Hence, exercise training is more beneficial to M than F in
      improving myocardial function following I-R injury.

PMID- 17507437
TI  - Neonatal immune challenge does not affect body weight regulation in rats.
AB  - The perinatal environment plays a crucial role in programming many aspects of
      adult physiology. Myriad stressors during pregnancy, from maternal immune
      challenge to nutritional deficiency, can alter long-term body weight set points
      of the offspring. In light of the increasing concern over body weight issues,
      such as obesity and anorexia, in modern societies and accumulating evidence that
      developmental stressors have long-lasting effects on other aspects of physiology
      (e.g., fever, pain), we explored the role of immune system activation during
      neonatal development and its impact on body weight regulation in adulthood. Here
      we present a thorough evaluation of the effects of immune system activation (LPS,
      100 microg/kg ip) at postnatal days 3, 7, or 14 on long-term body weight,
      adiposity, and body weight regulation after a further LPS injection (50 microg/kg
      ip) or fasting and basal and LPS-induced circulating levels of the appetite
      regulating proinflammatory cytokine leptin. We show that neonatal exposure to LPS
      at various times during the neonatal period has no long-term effects on growth,
      body weight, or adiposity. We also observed no effects on body weight regulation
      in response to a short fasting period or a further exposure to LPS. Despite
      reductions in circulating leptin levels in response to LPS during the neonatal
      period, no long-term effects on leptin were seen. These results convincingly
      demonstrate that adult body weight and weight regulation are, unlike many other
      aspects of adult physiology, resistant to programming by a febrile-dose neonatal
      immune challenge.

PMID- 17507438
TI  - High [Na+]i in cardiomyocytes from rainbow trout.
AB  - Intracellular Na(+)-concentration, [Na(+)](i) modulates excitation-contraction
      coupling of cardiac myocytes via the Na(+)/Ca(2+) exchanger (NCX). In
      cardiomyocytes from rainbow trout (Oncorhyncus mykiss), whole cell patch-clamp
      studies have shown that Ca(2+) influx via reverse-mode NCX contributes
      significantly to contraction when [Na(+)](i) is 16 mM but not 10 mM. However,
      physiological [Na(+)](i) has never been measured. We recorded [Na(+)](i) using
      the fluorescent indicator sodium-binding benzofuran isophthalate in freshly
      isolated atrial and ventricular myocytes from rainbow trout. We examined
      [Na(+)](i) at rest and during increases in contraction frequency across three
      temperatures that span those trout experience in nature (7, 14, and 21 degrees
      C). Surprisingly, we found that [Na(+)](i) was not different between atrial and
      ventricular cells. Furthermore, acute temperature changes did not affect
      [Na(+)](i) in resting cells. Thus, we report a resting in vivo [Na(+)](i) of 13.4
      mM for rainbow trout cardiomyocytes. [Na(+)](i) increased from rest with
      increases in contraction frequency by 3.2, 4.7, and 6.5% at 0.2, 0.5, and 0.8 Hz,
      respectively. This corresponds to an increase of 0.4, 0.6, and 0.9 mM at 0.2,
      0.5, and 0.8 Hz, respectively. Acute temperature change did not significantly
      affect the contraction-induced increase in [Na(+)](i). Our results provide the
      first measurement of [Na(+)](i) in rainbow trout cardiomyocytes. This
      surprisingly high [Na(+)](i) is likely to result in physiologically significant
      Ca(2+) influx via reverse-mode NCX during excitation-contraction coupling. We
      calculate that this Ca(2+)-source will decrease with the action potential
      duration as temperature and contraction frequency increases.

PMID- 17507439
TI  - Inspiratory resistance delays the reporting of symptoms with central hypovolemia:
      association with cerebral blood flow.
AB  - We tested the hypothesis that breathing through an inspiratory threshold device
      (ITD) during progressive central hypovolemia would protect cerebral perfusion and
      attenuate the reporting of presyncopal symptoms. Eight human subjects were
      exposed to lower-body negative pressure (LBNP) until the presence of symptoms
      while breathing through either an active ITD (-7 cmH(2)O impedance) or a sham ITD
      (0 cmH(2)O). Cerebral blood flow velocity (CBFV) was measured continuously via
      transcranial Doppler and analyzed in both time and frequency domains. Subjects
      were asked to report any subjective presyncopal symptoms (e.g., dizziness,
      nausea) at the conclusion of each LBNP exposure. Symptoms were coincident with
      physiological evidence of cardiovascular collapse (e.g., hypotension,
      bradycardia). Breathing on the active ITD increased LBNP tolerance time (mean +/-
      SE) from 2,014 +/- 106 s to 2,259 +/- 138 s (P = 0.006). We compared CBFV
      responses at the time of symptoms during the sham ITD trial with those at the
      same absolute time during the active ITD trial (when there were no symptoms).
      While there was no difference in mean CBFV at these time points (sham, 44 +/- 4
      cm/s vs. active, 47 +/- 4; P = 0.587), total oscillations (sum of high- and low
      frequency spectral power) of CBFV were higher (P = 0.004) with the active ITD
      (45.6 +/- 10.2 cm/s(2)) than the sham ITD (22.1 +/- 5.4 cm/s(2)). We conclude
      that greater oscillations around the same absolute level of mean CBFV are induced
      by inspiratory resistance and may contribute to the delay in symptoms and
      cardiovascular collapse that accompany progressive central hypovolemia.

PMID- 17507440
TI  - Minimal access cancer management.
AB  - Minimal access approaches in the treatment of a variety of solid tumors of the
      stomach, large bowel, and genitourinary system are now being advocated in several
      surgical specialty areas. The laparoscope has evolved from a diagnostic tool to a
      modality that allows for removal of tumors using small incisions and the
      application of pneumoperitoneum with carbon dioxide. Through studies using animal
      models and patient investigation, the immunologic benefits of laparoscopic cancer
      procedures appear to be beneficial when compared with conventional laparotomy.
      Overall benefits of analgesic reduction, more rapid postoperative recovery, and
      patient satisfaction are the byproducts of minimal access approaches. Patients
      with cancers of the stomach, colon, and kidney show similar long-term outcomes
      when compared with conventional open techniques. Caution, however, should be
      exercised in recommending laparoscopic approaches for routine management of
      primary tumors of the rectum and adrenal gland.

PMID- 17507441
TI  - Cancer risk elicitation and communication: lessons from the psychology of risk
      perception.
AB  - Cancer risk perceptions are a key predictor of risk-reduction practices, health
      behaviors, and processing of cancer information. Nevertheless, patients and the
      general public (as well as health care providers) exhibit a number of errors and
      biases in the way they think about risk, such that their risk perceptions and
      decisions deviate greatly from those prescribed by normative decision models and
      by experts in risk assessment. For example, people are more likely to engage in
      screening behaviors such as mammography when faced with loss-based messages than
      gain-framed messages, and they often ignore the base rate of a given disease when
      assessing their own risk of obtaining this disease. In this article, we review
      many of the psychological processes that underlie risk perception and discuss how
      these processes lead to such deviations. Among these processes are difficulties
      with use of numerical information (innumeracy), cognitive processes (eg, use of
      time-saving heuristics), motivational factors (eg, loss and regret aversion), and
      emotion. We conclude with suggestions for future research in the area, as well as
      implications for improving the elicitation and communication of personal cancer
      risk.

PMID- 17507442
TI  - Adjuvant treatment of colorectal cancer.
AB  - Colorectal cancer is the fourth most common noncutaneous malignancy in the United
      States and the second most frequent cause of cancer-related death. Approximately
      three quarters of patients are diagnosed with disease limited to the bowel wall
      or surrounding lymph nodes. Over the past decade, significant progress has been
      made in the treatment of localized colorectal cancer due to advances in surgery,
      radiotherapy, and chemotherapy. For patients with Stage III colon cancer, an
      overall survival benefit for fluorouracil-based chemotherapy has been firmly
      established, and recent data have shown further efficacy through the inclusion of
      oxaliplatin into adjuvant treatment programs. For patients with Stage II colon
      cancer, the use of adjuvant chemotherapy remains controversial, but may be
      appropriate in a subset of individuals at high risk for disease recurrence. In
      the treatment of patients with rectal cancer, improved outcomes have been noted
      with the use of total mesorectal excision and preoperative concurrent
      chemoradiotherapy. Current randomized clinical trials in the adjuvant therapy of
      colorectal cancer are examining the value of adding agents known to be active in
      metastatic disease, including those that modify specific molecular targets.

PMID- 17507443
TI  - Post concussional syndrome: all in the minds eye!

PMID- 17507444
TI  - Tracking the dynamics of secondary degeneration after stroke.

PMID- 17507445
TI  - Neurological picture. Carotid embolism.

PMID- 17507446
TI  - Neurological picture. Ruptured intracranial dermoid.

PMID- 17507447
TI  - Cortical cholinergic denervation is associated with depressive symptoms in
      Parkinson's disease and parkinsonian dementia.
AB  - AIM: To investigate the relationship between ratings of depressive symptoms and
      in vivo cortical acetylcholinesterase (AChE) activity in subjects with
      Parkinson's disease (PD) and parkinsonian dementia (PDem). METHODS: Subjects
      (with PD, n = 18, including subjects with PDem, n = 6, and normal controls, n =
      10) underwent [11C]methyl-4-piperidinyl propionate AChE positron emission
      tomography imaging and clinical assessment including the Cornell Scale for
      Depression in Dementia (CSDD). RESULTS: Subjects with PD and PDem had higher
      scores on the CSDD compared with normal controls: 7.3 (5.4) and 2.8 (2.6),
      respectively (F = 6.9, p = 0.01). Pooled analysis demonstrated a significant
      inverse correlation between cortical AChE activity and CSDD scores: R = -0.5, p =
      0.007. This correlation remained significant after controlling for Mini-Mental
      State Examination scores. CONCLUSION: Depressive symptomatology is associated
      with cortical cholinergic denervation in PD that tends to be more prominent when
      dementia is present.

PMID- 17507448
TI  - Illness perceptions and outcome in mild head injury: a longitudinal study.
AB  - BACKGROUND: A range of neuropathological and psychosocial factors have been
      implicated in the aetiology and maintenance of post-concussional syndrome (PCS),
      with a growing consensus in the literature that this is a complex, multifactorial
      condition. The role of patients' perceptions in PCS has not been examined to
      date. OBJECTIVE: This longitudinal study examines the role of illness perceptions
      in predicting outcome following mild head injury, controlling for severity of
      injury, post-traumatic stress symptoms, anxiety and depression, using a logistic
      regression analysis. METHOD: 73 patients were admitted to an accident and
      emergency department with mild head injury (Glasgow Coma Scale score 13-15; loss
      of consciousness <20 min; post-traumatic amnesia <24 h). Data on PCS
      symptomatology, illness perceptions, post-traumatic stress symptoms, anxiety and
      depression were collected after the injury and at the 3 month follow-up. Logistic
      regression analysis was used to evaluate predictors of outcome. RESULTS:
      Following a mild head injury, symptomatic patients who believe that their
      symptoms have serious negative consequences on their lives and will continue to
      do so, are at heightened risk of experiencing significant enduring post
      concussional symptoms (p<0.001). Adding measures of severity of injury, post
      traumatic stress symptoms, anxiety and depression to the regression model did not
      improve prediction of outcome. CONCLUSION: Whatever other physical or
      psychological factors may be involved, patients' perceptions of their illness
      early after head injury play a part in the persistence of PCS.

PMID- 17507449
TI  - Otfrid Foerster (1873-1941): one of the distinguished neuroscientists of his
      time.
AB  - Otfrid Foerster was a German neurologist and neurosurgeon who made innovative
      contributions to neurology and neurosurgery. Foerster performed the first
      electrocorticographic studies, the hyperventilation test on patient with epilepsy
      and described the atonic-astatic from of infantile cerebral palsy. He will be
      remembered best for the operation which bears his name (Foerster's operation) and
      on creating a cytoarchitectonic map of the human cerebral cortex. His most famous
      patient was Vladimir Ilyich Lenin (1870-1924).

PMID- 17507450
TI  - Anti-Ta-associated paraneoplastic encephalitis with occult testicular
      intratubular germ-cell neoplasia.

PMID- 17507451
TI  - Diffusion tensor tracking of fornix infarction.

PMID- 17507452
TI  - Stiff person syndrome (SPS), a basal ganglia disease? Striatal MRI lesions in a
      patient with SPS.

PMID- 17507453
TI  - Mobius syndrome in association with the REM sleep behaviour disorder.

PMID- 17507454
TI  - The M170 reflects a viewpoint-dependent representation for both familiar and
      unfamiliar faces.
AB  - The aim of this study was to determine the extent to which the neural
      representation of faces in visual cortex is viewpoint dependent or viewpoint
      invariant. Magnetoencephalography was used to measure evoked responses to faces
      during an adaptation paradigm. Using familiar and unfamiliar faces, we compared
      the amplitude of the M170 response to repeated images of the same face with
      images of different faces. We found a reduction in the M170 amplitude to repeated
      presentations of the same face image compared with images of different faces when
      shown from the same viewpoint. To establish if this adaptation to the identity of
      a face was invariant to changes in viewpoint, we varied the viewing angle of the
      face within a block. We found a reduction in response was no longer evident when
      images of the same face were shown from different viewpoints. This viewpoint
      dependent pattern of results was the same for both familiar and unfamiliar faces.
      These results imply that either the face-selective M170 response reflects an
      early stage of face processing or that the computations underlying face
      recognition depend on a viewpoint-dependent neuronal representation.

PMID- 17507455
TI  - The neural substrate of naming events: effects of processing demands but not of
      grammatical class.
AB  - Grammatical class is a fundamental property of language, and all natural
      languages distinguish between nouns and verbs. Brain activation studies have
      provided conflicting evidence concerning the neural substrates of noun and verb
      processing. A major limitation of many previous imaging studies is that they did
      not disentangle the impact of grammatical class from the differences in semantic
      correlates. In order to tease apart the role of semantic and grammatical factors,
      we performed a functional magnetic resonance imaging study presenting Italian
      speakers with pictures of events and asked them to name them as 1) Infinitive
      Verb (e.g., mangiare [to eat]); 2) Inflected Verb (e.g., mangia [she/he eats]);
      and 3) Action Noun (e.g., mangiata [the eating]). We did not find any verb
      specific activation. However, reliable left inferior frontal gyrus (IFG)
      activations were found when contrasting the Action Noun with the Infinitive Verb
      condition. A second-level analysis indicated then that activation in left IFG was
      greatest for Action Nouns, intermediate for Inflected Verbs, and least for
      Infinitive Verbs. We conclude that, when all other factors are controlled, nouns
      and verbs are processed by a common neural system. In the present case,
      differences in left IFG activation emerge as a consequence of increasing
      linguistic and/or general processing demands.

PMID- 17507456
TI  - Olfactory cues modulate facial attractiveness.
AB  - We report an experiment designed to investigate whether olfactory cues can
      influence people's judgments of facial attractiveness. Sixteen female
      participants judged the attractiveness of a series of male faces presented
      briefly on a computer monitor using a 9-point visual rating scale. While viewing
      each face, the participants were simultaneously presented with either clean air
      or else with 1 of 4 odorants (the odor was varied on a trial-by-trial basis) from
      a custom-built olfactometer. We included 2 pleasant odors (geranium and a male
      fragrance) and 2 unpleasant odors (rubber and body odor) as confirmed by pilot
      testing. The results showed that the participants rated the male faces as being
      significantly less attractive in the presence of an unpleasant odor than when the
      faces were presented together with a pleasant odor or with clean air (these
      conditions did not differ significantly). These results demonstrate the cross
      modal influence that unpleasant odors can have on people's judgments of facial
      attractiveness. Interestingly, this pattern of results was unaffected by whether
      the odors were body relevant (the body odor and the male fragrance) or not (the
      rubber and geranium odors).

PMID- 17507457
TI  - Mutation in CEP290 discovered for cat model of human retinal degeneration.
AB  - A mutation in the CEP290 gene is reported in a cat pedigree segregating for
      autosomal recessive (AR) late-onset photoreceptor degeneration (rdAc). An initial
      screen of 39 candidate genes and genomic locations failed to detect linkage to
      cat rdAc. Linkage was ultimately established on cat B4 with 15 simple tandem
      repeat markers (logarithm of odds [LOD] range 4.83-15.53, Theta = 0.0), in a
      region demonstrating conserved synteny to human chromosome 12, 84.9-90.63 Mb. The
      sequence of 10 genes with feline retinal expression was examined in affected and
      unaffected individuals. A single-nucleotide polymorphism was characterized in
      intron 50 of CEP290 (IVS50 + 9T>G) that creates a strong canonical splice donor
      site, resulting in a 4-bp insertion and frameshift in the mRNA transcript, with
      subsequent introduction of a stop codon and premature truncation of the protein.
      A population genetic survey of 136 cats demonstrated that the rdAc mutation is in
      low frequency in Abyssinian populations (0.13, Sweden; 0.07, United States) and
      absent in breeds of non-Abyssinian heritage. Mutations in CEP290 have recently
      been shown to cause two human diseases, Joubert syndrome, a syndromic retinal
      degeneration, and Leber's congenital amaurosis, an AR early-onset retinal
      dystrophy. Human AR retinitis pigmentosa is among the most common causes of
      retinal degeneration and blindness, with no therapeutic intervention available.
      This identification of a large animal model for human retinal blindness offers
      considerable promise in developing gene-based therapies.

PMID- 17507458
TI  - The adoption of innovations by provider organizations in health care.
AB  - Innovations in health care account for some of the most dramatic improvements in
      population health outcomes in the developed world as well as for a nontrivial
      proportion of growth in expenditures. Provider organizations are the adopters of
      many of these innovations, and understanding the factors that inhibit or
      facilitate their diffusion to and possible disengagement from these organizations
      is important in addressing cost, quality, and access issues. Given the importance
      of these issues, the purpose of this article is to (1) create a comprehensive
      census of studies examining the adoption of and disengagement from innovations in
      health care provider organizations; (2) organize these studies into an
      inductively derived classification scheme; (3) assess the studies' strengths and
      weaknesses; and (4) reflect on the implications of our review for future
      research.

PMID- 17507459
TI  - Determinants of implementation effectiveness: adapting a framework for complex
      innovations.
AB  - Many innovations in the health sector are complex, requiring coordinated use by
      multiple organizational members to achieve benefits. Often, complex innovations
      are adopted with great anticipation only to fail during implementation. The
      health services literature provides limited conceptual guidance to researchers
      and practitioners about implementation of complex innovations. In the present
      study, we adapt an organizational framework of innovation implementation
      developed and validated in a manufacturing setting and explore the extent to
      which it aptly characterizes implementation in health sector organizations.
      Through comparative case studies of four cancer clinical research networks, we
      illustrate how this conceptual framework captures key determinants of the
      implementation of new programs in cancer prevention and control (CP/C) research
      and helps explain observed differences in implementation effectiveness. Key
      determinants include management support and innovation-values fit, which
      contribute to an organizational "climate" for implementation. We explore the
      implications for researchers and managers.

PMID- 17507460
TI  - Persistence of high health care expenditures among children in Medicaid.
AB  - Cross-sectional studies show that a small percentage of children consume a large
      portion of the health care dollar. However, little is known about the persistence
      of high health care expenditures among children enrolled in Medicaid health
      maintenance organizations (HMOs) or in primary care case management (PCCM)
      programs. This study found substantial expenditure persistence during a 3-year
      period. Among Temporary Aid to Needy Families (TANF) children in HMOs in the top
      10 percent of the expenditure distribution in 2003, 34 percent remained in the
      top 10 percent in 2004, and 23 percent remained in the top 10 percent in 2005.
      Similar patterns were observed for TANF children in the PCCM. Expenditure
      persistence varied based on the enrollees' enabling and need characteristics,
      providing opportunities to identify children with high health care expenditures
      who may benefit from care coordination.

PMID- 17507461
TI  - Physician attitudes toward pay-for-quality programs: perspectives from the front
      line.
AB  - Pay-for-quality (P4Q) initiatives are becoming an increasingly popular mechanism
      for improving quality performance and reducing health care costs in the United
      States. Because these programs often target primary care physicians, it is
      important to understand how these physicians perceive and respond to P4Q to
      design successful programs going forward. This study reports results of a survey
      regarding attitudes toward P4Q among physicians participating in such programs in
      Massachusetts and California. Findings indicate physicians have generally
      positive attitudes toward the concept of P4Q, but are ambivalent about certain
      features of these programs as currently designed and implemented.

PMID- 17507462
TI  - Estimating the infectivity of CCR5-tropic simian immunodeficiency virus
      SIV(mac251) in the gut.
AB  - CD4+ T-cell depletion during acute human immunodeficiency virus infection occurs
      predominantly in the gastrointestinal mucosa. Using experimental data on
      SIV(mac251) viral load in blood and CD4+ T cells in the jejunum, we modeled the
      kinetics of CD4+ T-cell infection and death and estimated the viral infectivity.
      The infectivity of SIV(mac251) is higher than previously estimated for SHIV89.6P
      infection, but this higher infectivity is offset by a lower average peak viral
      load in SIV(mac251). Thus, the dynamics of target cell infection and death are
      remarkably similar between a CXCR4- and a CCR5-tropic infection in vivo.

PMID- 17507463
TI  - Lethal silver-haired bat rabies virus infection can be prevented by opening the
      blood-brain barrier.
AB  - Silver-haired bat rabies virus (SHBRV) infection induces a strong virus-specific
      immune response in the periphery of the host, but death is common due to the
      failure to open the blood-brain barrier (BBB) and deliver immune effectors to
      central nervous system (CNS) tissues. Mice with an SJL background are less
      susceptible to lethal infection with rabies viruses. In addition, these animals
      are known to have reduced hypothalamus-pituitary-adrenal (HPA) axis activity and
      an elevated capacity to mediate CNS inflammatory responses. We show here that
      approximately one-half of PLSJL mice survive an SHBRV infection that is
      invariably lethal for 129/SvEv mice. This difference is associated with the
      elevated capacity of PLSJL mice to mediate BBB permeability changes in response
      to the infection. The induction of more extensive BBB permeability and CNS
      inflammation in these animals results in greater virus clearance and improved
      survival. On the other hand, treatment of SHBRV-infected PLSJL mice with the
      steroid hormone dehydroepiandrosterone reduced BBB permeability changes and
      caused greater mortality. We conclude that the infiltration of immune effectors
      across the BBB is critical to surviving a rabies virus infection and that HPA
      axis activity may influence this process.

PMID- 17507464
TI  - Minimal region sufficient for genome dimerization in the human immunodeficiency
      virus type 1 virion and its potential roles in the early stages of viral
      replication.
AB  - It has been suggested that the dimer initiation site/dimer linkage sequence
      (DIS/DLS) region of the human immunodeficiency virus type 1 (HIV-1) RNA genome
      plays an important role at various stages of the viral life cycle. Recently we
      found that the duplication of the DIS/DLS region on viral RNA caused the
      production of partially monomeric RNAs in virions, indicating that this region
      indeed mediates RNA-RNA interaction. In this report, we followed up on this
      finding to identify the necessary and sufficient region for RNA dimerization in
      the virion of HIV-1. The region thus identified was 144 bases in length,
      extending from the junction of R/U5 and U5/L stem-loops to the end of SL4. The
      trans-acting responsive element, polyadenylation signal, primer binding site,
      upper stem-loop of U5/L, and SL2 were not needed for the function of this region.
      The insertion of this region into the ectopic location of the viral genome did
      not affect the level of virion production by transfection. However, the resultant
      virions contained monomerized genomes and showed drastic reductions in
      infectivity. A reduction was observed especially in the reverse transcription
      process. An attempt to generate a replication-competent virus with monomerized
      genome was performed by the long-term culture of mutant virus-infected cells. All
      recovered viruses were wild-type revertants, indicating a fatal defect of the
      mutation. These results suggest that genome dimerization or DIS/DLS itself also
      plays an important role in the early stages of virus infection.

PMID- 17507465
TI  - Evidence for cooperative transforming activity of the human pituitary tumor
      transforming gene and human T-cell leukemia virus type 1 Tax.
AB  - Aneuploidy is frequent in cancers. Recently it was found that pituitary tumor
      transforming gene (PTTG; also called Pds1p or securin) is overexpressed in many
      different tumors. Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus
      that primarily infects CD4+ T lymphocytes and causes adult T-cell leukemia. Here,
      we report that overexpression of human PTTG cooperated with the HTLV-I Tax
      oncoprotein in cellular transformation. Coexpression of Tax and PTTG enhanced
      chromosomal instability and neoplastic changes to levels greater than
      overexpression of either factor singularly. Cells that overexpressed both PTTG
      and Tax induced tumors more robustly in nude mice than cells that expressed
      either PTTG alone or Tax alone.

PMID- 17507466
TI  - Lipid rafts of primary endothelial cells are essential for Kaposi's sarcoma
      associated herpesvirus/human herpesvirus 8-induced phosphatidylinositol 3-kinase
      and RhoA-GTPases critical for microtubule dynamics and nuclear delivery of viral
      DNA but dispensable for binding and entry.
AB  - Early during de novo infection of human microvascular dermal endothelial (HMVEC
      d) cells, Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpesvirus 8
      [HHV-8]) induces the host cell's preexisting FAK, Src, phosphatidylinositol 3
      kinase (PI3-K), Rho-GTPases, Diaphanous-2 (Dia-2), Ezrin, protein kinase C-zeta,
      extracellular signal-regulated kinase 1/2 (ERK1/2), and NF-kappaB signal pathways
      that are critical for virus entry, nuclear delivery of viral DNA, and initiation
      of viral gene expression. Since several of these signal molecules are known to be
      associated with lipid raft (LR) domains, we investigated the role of LR during
      KSHV infection of HMVEC-d cells. Pretreatment of cells with LR-disrupting agents
      methyl beta-cyclo dextrin (MbetaCD) or nystatin significantly inhibited the
      expression of viral latent (ORF73) and lytic (ORF50) genes. LR disruption did not
      affect KSHV binding but increased viral DNA internalization. In contrast,
      association of internalized viral capsids with microtubules (MTs) and the
      quantity of infected nucleus-associated viral DNA were significantly reduced.
      Disorganized and disrupted MTs and thick rounded plasma membranes were observed
      in MbetaCD-treated cells. LR disruption did not affect KSHV-induced FAK and
      ERK1/2 phosphorylation; in contrast, it increased the phosphorylation of Src,
      significantly reduced the KSHV-induced PI3-K and RhoA-GTPase and NF-kappaB
      activation, and reduced the colocalizations of PI3-K and RhoA-GTPase with LRs.
      Biochemical characterization demonstrated the association of activated PI3-K with
      LR fractions which was inhibited by MbetaCD treatment. RhoA-GTPase activation was
      inhibited by PI3-K inhibitors, demonstrating that PI3-K is upstream to RhoA
      GTPase. In addition, colocalization of Dia-2, a RhoA-GTPase activated molecule
      involved in MT activation, with LR was reduced. KSHV-RhoA-GTPase mediated
      acetylation and aggregation of MTs were also reduced. Taken together, these
      studies suggest that LRs of endothelial cells play critical roles in KSHV
      infection and gene expression, probably due to their roles in modulating KSHV
      induced PI3-K, RhoA-GTPase, and Dia-2 molecules essential for postbinding and
      entry stages of infection such as modulation of microtubular dynamics, movement
      of virus in the cytoplasm, and nuclear delivery of viral DNA.

PMID- 17507468
TI  - Compensatory mutation partially restores fitness and delays reversion of escape
      mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic
      human immunodeficiency virus type 1 infection.
AB  - HLA-B*5703 is associated with effective immune control in human immunodeficiency
      virus type 1 (HIV-1) infection. Here we describe an escape mutation within the
      immunodominant HLA-B*5703-restricted epitope in chronic HIV-1 infection,
      KAFSPEVIPMF (Gag 162-172), and demonstrate that this mutation reduces viral
      replicative capacity. Reversion of this mutation following transmission to HLA
      B*5703-negative recipients was delayed by the compensatory mutation S165N within
      the same epitope. These data may help explain the observed association between
      HLA-B*5703 and long-term control of viremia.

PMID- 17507467
TI  - Coreceptor tropism in human immunodeficiency virus type 1 subtype D: high
      prevalence of CXCR4 tropism and heterogeneous composition of viral populations.
AB  - In human immunodeficiency virus type 1 (HIV-1) subtype B, CXCR4 coreceptor use
      ranges from approximately 20% in early infection to approximately 50% in advanced
      disease. Coreceptor use by non-subtype B HIV is less well characterized. We
      studied coreceptor tropism of subtype A and D HIV-1 collected from 68 pregnant,
      antiretroviral drug-naive Ugandan women (HIVNET 012 trial). None of 33 subtype A
      or 10 A/D-recombinant viruses used the CXCR4 coreceptor. In contrast, nine (36%)
      of 25 subtype D viruses used both CXCR4 and CCR5 coreceptors. Clonal analyses of
      the nine subtype D samples with dual or mixed tropism revealed heterogeneous
      viral populations comprised of X4-, R5-, and dual-tropic HIV-1 variants. In five
      of the six samples with dual-tropic strains, V3 loop sequences of dual-tropic
      clones were identical to those of cocirculating R5-tropic clones, indicating the
      presence of CXCR4 tropism determinants outside of the V3 loop. These dual-tropic
      variants with R5-tropic-like V3 loops, which we designated "dual-R," use CCR5
      much more efficiently than CXCR4, in contrast to dual-tropic clones with X4
      tropic-like V3 loops ("dual-X"). These observations have implications for
      pathogenesis and treatment of subtype D-infected individuals, for the association
      between V3 sequence and coreceptor tropism phenotype, and for understanding
      potential mechanisms of evolution from exclusive CCR5 use to efficient CXCR4 use
      by subtype D HIV-1.

PMID- 17507469
TI  - Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding,
      and neutralization.
AB  - Hepatitis C virus (HCV) is a major human pathogen that causes serious liver
      disease, including cirrhosis and hepatocellular carcinoma. The primary target
      cells of HCV are hepatocytes, and entry is restricted by interactions of the
      envelope glycoproteins, E1 and E2, with cellular receptors. E1 and E2 form
      noncovalently linked heterodimers and are heavily glycosylated. Glycans
      contribute to protein folding and transport as well as protein function. In
      addition, glycans associated with viral envelopes mask important functional
      domains from the immune system and attenuate viral immunogenicity. Here, we
      explored the role of N- and O-linked glycans on E2, which is the receptor binding
      subunit of the HCV envelope. We identified a number of glycans that are critical
      for viral entry. Importantly, we showed that the removal of several glycans
      significantly increased the inhibition of entry by sera from HCV-positive
      individuals. Only some of the glycans that affected entry and neutralization were
      also important for CD81 binding. Our results show that HCV envelope-associated
      glycans play a crucial role in masking functionally important regions of E2 and
      suggest a new strategy for eliciting highly neutralizing antibodies against this
      virus.

PMID- 17507470
TI  - Establishment of a poliovirus oral infection system in human poliovirus receptor
      expressing transgenic mice that are deficient in alpha/beta interferon receptor.
AB  - Poliovirus (PV) is easily transferred to humans orally; however, no rodent model
      for oral infections has been developed because of the alimentary tract's low
      sensitivity to the virus. Here we showed that PV is inactivated by the low pH of
      the gastric contents in mice. The addition of 3% NaHCO3 to the viral inoculum
      increased the titer of virus reaching the small intestine through the stomach
      after intragastric inoculation of PV. Transgenic mice (Tg) carrying the human PV
      receptor (hPVR/CD155) gene and lacking the alpha/beta interferon receptor (IFNAR)
      gene (hPVR-Tg/IfnarKO) were sensitive to the oral administration of PV with 3%
      NaHCO3, whereas hPVR-Tg expressing IFNAR were much less sensitive. The virus was
      detected in the epithelia of the small intestine and proliferated in the
      alimentary tract of hPVR-Tg/IfnarKO. By the ninth day after the administration of
      a virulent PV, the mice had died. These results suggest that IFNAR plays an
      important role in determining permissivity in the alimentary tract as well as the
      generation of virus-specific immune responses to PV via the oral route. Thus,
      hPVR-Tg/IfnarKO are considered to be the first oral infection model for PV,
      although levels of anti-PV antibodies were not elevated dramatically in serum and
      intestinal secretions of surviving mice when hPVR-Tg/IfnarKO were administered an
      attenuated PV.

PMID- 17507471
TI  - Distance-dependent processing of adeno-associated virus type 5 RNA is controlled
      by 5' exon definition.
AB  - Adeno-associated virus type 5 (AAV5) is unique among human AAV serotypes in that
      it uses a polyadenylation site [(pA)p] within the single small intron in the
      center of the genome. We previously reported that inhibition of polyadenylation
      at (pA)p, necessary for read-through of P41-generated capsid gene pre-mRNAs which
      are subsequently spliced, requires binding of U1 snRNP to the upstream donor.
      Inhibition was reduced as the distance between the cap site and the donor was
      increased (increasing the size of the 5' exon). Here, we have demonstrated that
      U1-70K is a key component of U1 snRNP that mediates inhibition of polyadenylation
      at (pA)p. Furthermore, introduction of a U-rich stretch, predicted to target TIA
      1 and thus increase the affinity of U1 snRNP binding to the intervening donor
      site, significantly augmented inhibition of (pA)p, while depletion of TIA-1 by
      siRNA increased (pA)p read-through. Finally, artificially tethering the cap
      binding complex (CBC) components CBP80 and CBP20 upstream of the intron donor
      increased inhibition of polyadenylation at (pA)p. Our results suggest that
      interaction with the CBC strengthens U1 snRNP binding to the downstream intron
      donor in a manner inversely proportional to the size of the 5' exon, thus
      governing the competition between intron splicing and polyadenylation at (pA)p.
      This competition must be optimized to program both the levels of polyadenylation
      of P7- and P19-generated RNA at (pA)p required to produce proper levels of the
      essential Rep proteins and the splicing of P41-generated RNAs to produce the
      proper ratio of capsid proteins during AAV5 infection.

PMID- 17507472
TI  - Ku80 participates in the targeting of retroviral transgenes to the chromatin of
      CHO cells.
AB  - The heterodimer Ku70/80 Ku is the DNA-binding component of the DNA-PK complex
      required for the nonhomologous end-joining pathway. It participates in numerous
      nuclear processes, including telomere and chromatin structure maintenance,
      replication, and transcription. Ku interacts with retroviral preintegration
      complexes and is thought to interfere with the retroviral replication cycle, in
      particular the formation of 2-long terminal repeat (LTR) viral DNA circles, viral
      DNA integration, and transcription. We describe here the effect of Ku80 on both
      provirus integration and the resulting transgene expression in cells transduced
      with retroviral vectors. We found that transgene expression was systematically
      higher in Ku80-deficient xrs6 cells than in Ku80-expressing CHO cells. This
      higher expression was observed irrespective of the presence of the viral LTR and
      was also not related to the nature of the promoter. Real-time PCR monitoring of
      the early viral replicative steps demonstrated that the absence of Ku80 does not
      affect the efficiency of transduction. We analyzed the transgene distributions
      localization in nucleus by applying a three-dimensional reconstruction model to
      two-dimensional fluorescence in situ hybridization images. This indicated that
      the presence of Ku80 resulted in a bias toward the transgenes being located at
      the periphery of the nucleus associated with their being repressed; in the
      absence of this factor the transgenes tend to be randomly distributed and
      actively expressed. Therefore, although not strictly required for retroviral
      integration, Ku may be involved in targeting retroviral elements to chromatin
      domains prone to gene silencing.

PMID- 17507473
TI  - Surface-exposed adeno-associated virus Vp1-NLS capsid fusion protein rescues
      infectivity of noninfectious wild-type Vp2/Vp3 and Vp3-only capsids but not that
      of fivefold pore mutant virions.
AB  - Over the past 2 decades, significant effort has been dedicated to the development
      of adeno-associated virus (AAV) as a vector for human gene therapy. However,
      understanding of the virus with respect to the functional domains of the capsid
      remains incomplete. In this study, the goal was to further examine the role of
      the unique Vp1 N terminus, the N terminus plus the recently identified nuclear
      localization signal (NLS) (J. C. Grieger, S. Snowdy, and R. J. Samulski, J. Virol
      80:5199-5210, 2006), and the virion pore at the fivefold axis in infection. We
      generated two Vp1 fusion proteins (Vp1 and Vp1NLS) linked to the 8-kDa chemokine
      domain of rat fractalkine (FKN) for the purpose of surface exposure upon assembly
      of the virion, as previously described (K. H. Warrington, Jr., O. S. Gorbatyuk,
      J. K. Harrison, S. R. Opie, S. Zolotukhin, and N. Muzyczka, J. Virol 78:6595
      6609, 2004). The unique Vp1 N termini were found to be exposed on the surfaces of
      these capsids and maintained their phospholipase A2 (PLA2) activity, as
      determined by native dot blot Western and PLA2 assays, respectively.
      Incorporation of the fusions into AAV type 2 capsids lacking a wild-type Vp1,
      i.e., Vp2/Vp3 and Vp3 capsid only, increased infectivity by 3- to 5-fold (Vp1FKN)
      and 10- to 100-fold (Vp1NLSFKN), respectively. However, the surface-exposed
      fusions did not restore infectivity to AAV virions containing mutations at a
      conserved leucine (Leu336Ala, Leu336Cys, or Leu336Trp) located at the base of the
      fivefold pore. EM analyses suggest that Leu336 may play a role in global
      structural changes to the virion directly impacting downstream conformational
      changes essential for infectivity and not only have local effects within the
      pore, as previously suggested.

PMID- 17507474
TI  - A conserved region in the F(2) subunit of paramyxovirus fusion proteins is
      involved in fusion regulation.
AB  - Paramyxoviruses utilize both an attachment protein and a fusion (F) protein to
      drive virus-cell and cell-cell fusion. F exists functionally as a trimer of two
      disulfide-linked subunits: F(1) and F(2). Alignment and analysis of a set of
      paramyxovirus F protein sequences identified three conserved blocks (CB): one in
      the fusion peptide/heptad repeat A domain, known to play important roles in
      fusion promotion, one in the region between the heptad repeats of F(1) (CBF(1))
      (A. E. Gardner, K. L. Martin, and R. E. Dutch, Biochemistry 46:5094-5105, 2007),
      and one in the F(2) subunit (CBF(2)). To analyze the functions of CBF(2), alanine
      substitutions at conserved positions were created in both the simian virus 5
      (SV5) and Hendra virus F proteins. A number of the CBF(2) mutations resulted in
      folding and expression defects. However, the CBF(2) mutants that were properly
      expressed and trafficked had altered fusion promotion activity. The Hendra virus
      CBF(2) Y79A and P89A mutants showed significantly decreased levels of fusion,
      whereas the SV5 CBF(2) I49A mutant exhibited greatly increased cell-cell fusion
      relative to that for wild-type F. Additional substitutions at SV5 F I49 suggest
      that both side chain volume and hydrophobicity at this position are important in
      the folding of the metastable, prefusion state and the subsequent triggering of
      membrane fusion. The recently published prefusogenic structure of parainfluenza
      virus 5/SV5 F (H. S. Yin et al., Nature 439:38-44, 2006) places CBF(2) in direct
      contact with heptad repeat A. Our data therefore indicate that this conserved
      region plays a critical role in stabilizing the prefusion state, likely through
      interactions with heptad repeat A, and in triggering membrane fusion.

PMID- 17507475
TI  - Varicella-Zoster virus IE63, a major viral latency protein, is required to
      inhibit the alpha interferon-induced antiviral response.
AB  - Varicella-zoster virus (VZV) open reading frame 63 (ORF63) is the most abundant
      transcript expressed during latency in human sensory ganglia. VZV with ORF63
      deleted is impaired for replication in melanoma cells and fibroblasts and for
      latency in rodents. We found that replication of the ORF63 deletion mutant is
      fully complemented in U2OS cells, which have been shown to complement the growth
      of herpes simplex virus type 1 (HSV-1) ICP0 mutants. Since HSV-1 ICP0 mutants are
      hypersensitive to alpha interferon (IFN-alpha), we examined the effect of IFN
      alpha on VZV replication. Replication of the ORF63 mutant in melanoma cells was
      severely inhibited in the presence of IFN-alpha, in contrast to other VZV mutants
      that were similarly impaired for replication or to parental virus. The VZV ORF63
      mutant was not hypersensitive to IFN-gamma. IFN-alpha inhibited viral-gene
      expression in cells infected with the ORF63 mutant at a posttranscriptional
      level. Since IFN-alpha stimulates gene products that can phosphorylate the alpha
      subunit of eukaryotic initiation factor 2 (eIF-2alpha) and inhibit translation,
      we determined whether cells infected with the ORF63 mutant had increased
      phosphorylation of eIF-2alpha compared with cells infected with parental virus.
      While phosphorylated eIF-2alpha was undetectable in uninfected cells or cells
      infected with parental virus, it was present in cells infected with the ORF63
      mutant. Conversely, expression of IE63 (encoded by ORF63) in the absence of other
      viral proteins inhibited phosphorylation of eIF-2alpha. Since IFN-alpha has been
      shown to limit VZV replication in human skin xenografts, the ability of VZV IE63
      to block the effects of the cytokine may play a critical role in VZV
      pathogenesis.

PMID- 17507476
TI  - Selection of mutations in the connection and RNase H domains of human
      immunodeficiency virus type 1 reverse transcriptase that increase resistance to
      3'-azido-3'-dideoxythymidine.
AB  - Recent work indicates that mutations in the C-terminal domains of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) increase 3'
      azido-3'-dideoxythymidine (AZT) resistance. Because it is not known whether AZT
      selects for mutations outside of the polymerase domain of RT, we carried out in
      vitro experiments in which HIV-1(LAI) or AZT-resistant HIV-1(LAI)
      (M41L/L210W/T215Y) was passaged in MT-2 cells in increasing concentrations of
      AZT. The first resistance mutations to appear in HIV-1(LAI) were two polymerase
      domain thymidine analog mutations (TAMs), D67N and K70R, and two novel mutations,
      A371V in the connection domain and Q509L in the RNase H domain, that together
      conferred up to 90-fold AZT resistance. Thereafter, the T215I mutation appeared
      but was later replaced by T215F, resulting in a large increase in AZT resistance
      ( approximately 16,000-fold). Mutations in the connection and RNase H domains
      were not selected starting with AZT-resistant virus (M41L/L210W/T215Y). The roles
      of A371V and Q509L in AZT resistance were confirmed by site-directed mutagenesis:
      A371V and Q509L together increased AZT resistance approximately 10- to 50-fold in
      combination with TAMs (M41L/L210W/T215Y or D67N/K70R/T215F) but had a minimal
      effect without TAMs (1.7-fold). A371V and Q509L also increased cross-resistance
      with TAMs to lamivudine and abacavir, but not stavudine or didanosine. These
      results provide the first evidence that mutations in the connection and RNase H
      domains of RT can be selected in vitro by AZT and confer greater AZT resistance
      and cross-resistance to nucleoside RT inhibitors in combination with TAMs in the
      polymerase domain.

PMID- 17507478
TI  - GxxxG motif of severe acute respiratory syndrome coronavirus spike glycoprotein
      transmembrane domain is not involved in trimerization and is not important for
      entry.
AB  - Recently, a paper was published in which it was proposed that the GxxxG motif of
      the severe acute respiratory syndrome (SARS) coronavirus spike (S) protein
      transmembrane domain plays a vital role in oligomerization of the protein (E.
      Arbely, Z. Granot, I. Kass, J. Orly, and I. T. Arkin, Biochemistry 45:11349
      11356, 2006). Here, we show that the GxxxG motif is not involved in SARS S
      oligomerization by trimerization analysis of S GxxxG mutant proteins. In
      addition, the capability of S to mediate entry of SARS S-pseudotyped particles
      overall was affected moderately in the mutant proteins, also arguing for a
      nonvital role for the GxxxG motif in SARS coronavirus entry.

PMID- 17507477
TI  - Insulin-like growth factor II receptor-mediated intracellular retention of
      cathepsin B is essential for transformation of endothelial cells by Kaposi's
      sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the pathological agent of
      Kaposi's sarcoma (KS), a tumor characterized by aberrant proliferation of
      endothelial-cell-derived spindle cells. Since in many cancers tumorigenesis is
      associated with an increase in the activity of the cathepsin family, we studied
      the role of cathepsins in KS using an in vitro model of KSHV-mediated endothelial
      cell transformation. Small-molecule inhibitors and small interfering RNA (siRNA)
      targeting CTSB, but not other cathepsins, inhibited KSHV-induced postconfluent
      proliferation and the formation of spindle cells and foci of dermal microvascular
      endothelial cells. Interestingly, neither CTSB mRNA nor CTSB protein levels were
      induced in endothelial cells latently infected with KSHV. Secretion of CTSB was
      strongly diminished upon KSHV infection. Increased targeting of CTSB to endosomes
      was caused by the induction by KSHV of the expression of insulin-like growth
      factor-II receptor (IGF-IIR), a mannose-6-phosphate receptor (M6PR) that binds to
      cathepsins. Inhibition of IGF-IIR/M6PR expression by siRNA released CTSB for
      secretion. In contrast to the increased cathepsin secretion observed in most
      other tumors, viral inhibition of CTSB secretion via induction of an M6PR is
      crucial for the transformation of endothelial cells.

PMID- 17507479
TI  - Synthetic reconstruction of zoonotic and early human severe acute respiratory
      syndrome coronavirus isolates that produce fatal disease in aged mice.
AB  - The severe acute respiratory syndrome (SARS) epidemic was characterized by high
      mortality rates in the elderly. The molecular mechanisms that govern enhanced
      susceptibility of elderly populations are not known, and robust animal models are
      needed that recapitulate the increased pathogenic phenotype noted with increasing
      age. Using synthetic biology and reverse genetics, we describe the construction
      of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike
      glycoproteins that are representative of zoonotic strains found in palm civets
      and raccoon dogs, as well as isolates spanning the early, middle, and late phases
      of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell
      culture and demonstrated variable sensitivities to neutralization with
      antibodies. The human but not the zoonotic variants replicated efficiently in
      human airway epithelial cultures, supporting earlier hypotheses that zoonotic
      isolates are less pathogenic in humans but can evolve into highly pathogenic
      strains. All viruses replicated efficiently, but none produced clinical disease
      or death in young animals. In contrast, severe clinical disease, diffuse alveolar
      damage, hyaline membrane formation, alveolitis, and death were noted in 12-month
      old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase
      GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog
      strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic
      spike glycoproteins will provide heterologous challenge models for testing
      vaccine efficacy against zoonotic reintroductions as well as provide the
      appropriate model system for elucidating the complex virus-host interactions that
      contribute to more-severe and fatal SARS-CoV disease and acute respiratory
      distress in the elderly.

PMID- 17507480
TI  - MyD88-dependent immune activation mediated by human immunodeficiency virus type 1
      encoded Toll-like receptor ligands.
AB  - Immune activation is a major characteristic of human immunodeficiency virus type
      1 (HIV-1) infection and a strong prognostic factor for HIV-1 disease progression.
      The underlying mechanisms leading to immune activation in viremic HIV-1
      infection, however, are not fully understood. Here we show that, following the
      initiation of highly active antiretroviral therapy, the immediate decline of
      immune activation is closely associated with the reduction of HIV-1 viremia,
      which suggests a direct contribution of HIV-1 itself to immune activation. To
      propose a mechanism, we demonstrate that the single-stranded RNA of HIV-1 encodes
      multiple uridine-rich Toll-like receptor 7/8 (TLR7/8) ligands that induce strong
      MyD88-dependent plasmacytoid dendritic cell and monocyte activation, as well as
      accessory cell-dependent T-cell activation. HIV-1-encoded TLR ligands may,
      therefore, directly contribute to the immune activation observed during viremic
      HIV-1 infection. These data provide an initial rationale for inhibiting the TLR
      pathway to directly reduce the chronic immune activation induced by HIV-1 and the
      associated immune pathogenesis.

PMID- 17507481
TI  - Roles of phosphatidylinositol 3-kinase and NF-kappaB in human cytomegalovirus
      mediated monocyte diapedesis and adhesion: strategy for viral persistence.
AB  - Infected peripheral blood monocytes are proposed to play a key role in the
      hematogenous dissemination of human cytomegalovirus (HCMV) to tissues, a critical
      step in the establishment of HCMV persistence and the development of HCMV
      associated diseases. We recently provided evidence for a unique strategy involved
      in viral dissemination: HCMV infection of primary human monocytes promotes their
      transendothelial migration and differentiation into proinflammatory macrophages
      permissive for the replication of the original input virus. To decipher the
      mechanism of hematogenous spread, we focused on the viral dysregulation of early
      cellular processes involved in transendothelial migration. Here, we present
      evidence that both phosphatidylinositol 3-kinase [PI(3)K] and NF-kappaB
      activities were crucial for the HCMV induction of monocyte motility and firm
      adhesion to endothelial cells. We found that the beta(1) integrins, the beta(2)
      integrins, intracellular adhesion molecule 1 (ICAM-1), and ICAM-3 were
      upregulated following HCMV infection and that they played a key role in the firm
      adhesion of infected monocytes to the endothelium. The viral regulation of
      adhesion molecule expression is complex, with PI(3)K and NF-kappaB affecting the
      expression of each adhesion molecule at different stages of the expression
      cascade. Our data demonstrate key roles for PI(3)K and NF-kappaB signaling in the
      HCMV-induced cellular changes in monocytes and identify the biological rationale
      for the activation of these pathways in infected monocytes, which together
      suggest a mechanism for how HCMV promotes viral spread to and persistence within
      host organs.

PMID- 17507482
TI  - A naturally occurring splice variant of CXCL12/stromal cell-derived factor 1 is a
      potent human immunodeficiency virus type 1 inhibitor with weak chemotaxis and
      cell survival activities.
AB  - CXCL12/stromal cell-derived factor 1 is a member of the CXC family of chemokines
      that plays an important role in hematopoiesis and signals through CXCR4 and
      CXCR7. Two splice variants of human CXCL12 (CXCL12alpha and CXCL12beta) induce
      chemotaxis of CXCR4(+) cells and inhibit X4 infection. Recent studies described
      four other novel splice variants of human CXCL12; however, their antiviral
      activities were not investigated. We constructed and expressed all of the CXCL12
      splice variants in Escherichia coli. Recombinant proteins were purified through a
      His affinity column, and their biological properties were analyzed. All six
      CXCL12 variants induced chemotaxis of CXCR4(+) and CXCR7(+) cell lines.
      Enhancement of survival and replating capacity of human hematopoietic progenitor
      cells were observed with CXCL12alpha, CXCL12beta, and CXCL12epsilon but not with
      the other variants. CXCL12gamma showed the greatest antiviral activity in X4
      inhibition assays and the weakest chemotaxis activity through CXCR4. The order of
      potency in X4 inhibition assays was as follows: CXCL12gamma > CXCL12beta >
      CXCL12alpha > CXCL12theta > CXCL12epsilon > CXCL12delta. The order of anti-human
      immunodeficiency virus (HIV) activity was associated with the number of BBXB
      motifs present in each variant; the most potent inhibitor was CXCL12gamma, with
      five BBXB domains. The results suggest that the different C termini of CXCL12
      variants may contain important molecular determinants for the observed
      differences in antiviral effects and other biological functions. These studies
      implicate CXCL12gamma as a potent HIV-1 entry inhibitor with significantly
      reduced chemotaxis activity and small or absent effects on progenitor cell
      survival or replating capacity, providing important insight into the structure
      function relationships of CXCL12.

PMID- 17507483
TI  - High-avidity monoclonal antibodies against the human scavenger class B type I
      receptor efficiently block hepatitis C virus infection in the presence of high
      density lipoprotein.
AB  - The human scavenger class B type 1 receptor (SR-B1/Cla1) was identified as a
      putative receptor for hepatitis C virus (HCV) because it binds to soluble
      recombinant HCV envelope glycoprotein E2 (sE2). High-density lipoprotein (HDL), a
      natural SR-B1 ligand, was shown to increase the in vitro infectivity of
      retroviral pseudoparticles bearing HCV envelope glycoproteins and of cell culture
      derived HCV (HCVcc), suggesting that SR-B1 promotes viral entry in an HDL
      dependent manner. To determine whether SR-B1 participates directly in HCV
      infection or facilitates HCV entry through lipoprotein uptake, we generated a
      panel of monoclonal antibodies (MAbs) against native human SR-B1. Two of them,
      3D5 and C167, bound to conformation-dependent SR-B1 determinants and inhibited
      the interaction of sE2 with SR-B1. These antibodies efficiently blocked HCVcc
      infection of Huh-7.5 hepatoma cells in a dose-dependent manner. To examine the
      role of HDL in SR-B1-mediated HCVcc infection, we set up conditions for HCVcc
      production and infection in serum-free medium. HCVcc efficiently infected Huh-7.5
      cells in the absence of serum lipoproteins, and addition of HDL led to a twofold
      increase in infectivity. However, the HDL-induced enhancement of infection had no
      impact on the neutralization potency of MAb C167, despite its ability to inhibit
      both HDL binding to cells and SR-B1-mediated lipid transfer. Of note, MAb C167
      also potently blocked Huh-7.5 infection by an HCV strain recovered from HCVcc
      infected chimpanzees. These results demonstrate that SR-B1 is essential for
      infection with HCV produced in vitro and in vivo and suggest the possible use of
      anti-SR-B1 antibodies as therapeutic agents.

PMID- 17507484
TI  - Hepatitis C virus induces proteolytic cleavage of sterol regulatory element
      binding proteins and stimulates their phosphorylation via oxidative stress.
AB  - Hepatic steatosis is a common histological feature of chronic hepatitis C.
      Hepatitis C virus (HCV) gene expression has been shown to alter host cell
      cholesterol/lipid metabolism and thus induce hepatic steatosis. Since sterol
      regulatory element binding proteins (SREBPs) are major regulators of lipid
      metabolism, we sought to determine whether genotype 2a-based HCV infection
      induces the expression and posttranslational activation of SREBPs. HCV infection
      stimulates the expression of genes related to lipogenesis. HCV induces the
      proteolytic cleavage of SREBPs. HCV core and NS4b derived from genotype 3a are
      also individually capable of inducing the proteolytic processing of SREBPs.
      Further, we demonstrate that HCV stimulates the phosphorylation of SREBPs. Our
      studies show that HCV-induced oxidative stress and subsequent activation of the
      phosphatidylinositol 3-kinase (PI3-K)-Akt pathway and inactivation
      (phosphorylation) of PTEN (phosphatase and tensin homologue) mediate the
      transactivation of SREBPs. HCV-induced SREBP-1 and -2 activities were sensitive
      to antioxidant (pyrrolidine dithiocarbamate), Ca(2+) chelator 1,2
      bis(aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-tetra(acetoxymethyl) ester
      (BAPTA-AM), and PI3-K inhibitor (LY294002). Collectively, these studies provide
      insight into the mechanisms of hepatic steatosis associated with HCV infection.

PMID- 17507485
TI  - Characterization of low-pathogenic H5 subtype influenza viruses from Eurasia:
      implications for the origin of highly pathogenic H5N1 viruses.
AB  - Highly pathogenic avian influenza (HPAI) H5N1 viruses are now endemic in many
      Asian countries, resulting in repeated outbreaks in poultry and increased cases
      of human infection. The immediate precursor of these HPAI viruses is believed to
      be A/goose/Guangdong/1/96 (Gs/GD)-like H5N1 HPAI viruses first detected in
      Guangdong, China, in 1996. From 2000 onwards, many novel reassortant H5N1
      influenza viruses or genotypes have emerged in southern China. However,
      precursors of the Gs/GD-like viruses and their subsequent reassortants have not
      been fully determined. Here we characterize low-pathogenic avian influenza (LPAI)
      H5 subtype viruses isolated from poultry and migratory birds in southern China
      and Europe from the 1970s to the 2000s. Phylogenetic analyses revealed that Gs/GD
      like virus was likely derived from an LPAI H5 virus in migratory birds. However,
      its variants arose from multiple reassortments between Gs/GD-like virus and
      viruses from migratory birds or with those Eurasian viruses isolated in the
      1970s. It is of note that unlike HPAI H5N1 viruses, those recent LPAI H5 viruses
      have not become established in aquatic or terrestrial poultry. Phylogenetic
      analyses revealed the dynamic nature of the influenza virus gene pool in Eurasia
      with repeated transmissions between the eastern and western extremities of the
      continent. The data also show reassortment between influenza viruses from
      domestic and migratory birds in this region that has contributed to the expanded
      diversity of the influenza virus gene pool among poultry in Eurasia.

PMID- 17507486
TI  - Conserved changes in envelope function during human immunodeficiency virus type 1
      coreceptor switching.
AB  - We studied the evolution of human immunodeficiency virus type 1 (HIV-1) envelope
      function during the process of coreceptor switching from CCR5 to CXCR4. Site
      directed mutagenesis was used to introduce most of the possible intermediate
      mutations in the envelope for four distinct coreceptor switch mutants, each with
      a unique pattern of CCR5 and CXCR4 utilization that extended from highly
      efficient use of both coreceptors to sole use of CXCR4. Mutated envelopes with
      some preservation of entry function on either CCR5- or CXCR4-expressing target
      cells were further characterized for their sensitivity to CCR5 or CXCR4
      inhibitors, soluble CD4, and the neutralizing antibodies b12-IgG and 4E10. A
      subset of mutated envelopes was also studied in direct CD4 or CCR5 binding assays
      and in envelope-mediated fusion reactions. Coreceptor switch intermediates
      displayed increased sensitivity to CCR5 inhibitors (except for a few envelopes
      with mutations in V2 or C2) that correlated with a loss in CCR5 binding. As use
      of CXCR4 improved, infection mediated by the mutated envelopes became more
      resistant to soluble CD4 inhibition and direct binding to CD4 increased. These
      changes were accompanied by increasing resistance to the CXCR4 inhibitor AMD3100.
      Sensitivity to neutralizing antibody was more variable, although infection of
      CXCR4-expressing targets was generally more sensitive to neutralization by both
      b12-IgG and 4E10 than infection of CCR5-expressing target cells. These changes in
      envelope function were uniform in all four series of envelope mutations and thus
      were independent of the final use of CCR5 and CXCR4. Decreased CCR5 and increased
      CD4 binding appear to be common features of coreceptor switch intermediates.

PMID- 17507487
TI  - Identification of novel rodent herpesviruses, including the first
      gammaherpesvirus of Mus musculus.
AB  - Rodent herpesviruses such as murine cytomegalovirus (host, Mus musculus), rat
      cytomegalovirus (host, Rattus norvegicus), and murine gammaherpesvirus 68 (hosts,
      Apodemus species) are important tools for the experimental study of human
      herpesvirus diseases. However, alphaherpesviruses, roseoloviruses, and
      lymphocryptoviruses, as well as rhadinoviruses, that naturally infect Mus
      musculus (house mouse) and other Old World mice are unknown. To identify hitherto
      unknown rodent-associated herpesviruses, we captured M. musculus, R. norvegicus,
      and 14 other rodent species in several locations in Germany, the United Kingdom,
      and Thailand. Samples of trigeminal ganglia, dorsal root ganglia, brains,
      spleens, and other organs, as well as blood, were analyzed with a degenerate
      panherpesvirus PCR targeting the DNA polymerase (DPOL) gene. Herpesvirus-positive
      samples were subjected to a second degenerate PCR targeting the glycoprotein B
      (gB) gene. The sequences located between the partial DPOL and gB sequences were
      amplified by long-distance PCR and sequenced, resulting in a contiguous sequence
      of approximately 3.5 kbp. By DPOL PCR, we detected 17 novel betaherpesviruses and
      21 novel gammaherpesviruses but no alphaherpesvirus. Of these 38 novel
      herpesviruses, 14 were successfully analyzed by the complete bigenic approach.
      Most importantly, the first gammaherpesvirus of Mus musculus was discovered (Mus
      musculus rhadinovirus 1 [MmusRHV1]). This virus is a member of a novel group of
      rodent gammaherpesviruses, which is clearly distinct from murine herpesvirus 68
      like rodent gammaherpesviruses. Multigenic phylogenetic analysis, using an 8-kbp
      locus, revealed that MmusRHV1 diverged from the other gammaherpesviruses soon
      after the evolutionary separation of Epstein-Barr virus-like lymphocryptoviruses
      from human herpesvirus 8-like rhadinoviruses and alcelaphine herpesvirus 1-like
      macaviruses.

PMID- 17507489
TI  - Productive human immunodeficiency virus type 1 assembly takes place at the plasma
      membrane.
AB  - Gag proteins are necessary and sufficient to direct human immunodeficiency virus
      type 1 (HIV-1) particle assembly and budding. Recent evidence suggests that Gag
      targeting to late endosomal/multivesicular body (LE/MVB) compartments occurs
      prior to viral particle budding at the plasma membrane (PM). However, the route
      that Gag follows before reaching its steady-state destinations still remains a
      subject of debate. Using a subcellular fractionation method that separates PM
      from LE/MVB combined with pulse-chase labeling, we analyzed Gag trafficking in
      HIV-1-producing HEK 293T cells. Our results reveal that the majority of newly
      synthesized Gag is primarily targeted to the PM. While PM-targeted Gag was
      efficiently released, a significant fraction of the remaining cell surface
      associated Gag was found to be subsequently internalized to LE/MVB, where it
      accumulated, thus accounting for the majority of LE/MVB-associated Gag.
      Importantly, this accumulation of Gag in LE/MVB was found to be cholesterol
      dependent since it was sensitive to the sterol-binding drugs filipin and methyl
      beta-cyclodextrin. These results point towards the PM as being the primary site
      of productive HIV-1 assembly in cells that also support Gag accumulation in
      intracellular compartments.

PMID- 17507488
TI  - Virus subtype-specific features of natural simian immunodeficiency virus SIVsmm
      infection in sooty mangabeys.
AB  - Simian immunodeficiency virus (SIV) SIV(smm) naturally infects sooty mangabeys
      (SMs) and is the source virus of pathogenic infections with human
      immunodeficiency virus type 2 (HIV-2) and SIV(mac) of humans and macaques,
      respectively. In previous studies we characterized SIV(smm) diversity in
      naturally SIV-infected SMs and identified nine different phylogenetic subtypes
      whose genetic distances are similar to those reported for the different HIV-1
      group M subtypes. Here we report that, within the colony of SMs housed at the
      Yerkes National Primate Research Center, at least four SIV(smm) subtypes
      cocirculate, with the vast majority of animals infected with SIV(smm) subtype 1,
      2, or 3, resulting in the emergence of occasional recombinant forms. While
      SIV(smm)-infected SMs show a typically nonpathogenic course of infection, we have
      observed that different SIV(smm) subtypes are in fact associated with specific
      immunologic features. Notably, while subtypes 1, 2, and 3 are associated with a
      very benign course of infection and preservation of normal CD4+ T-cell counts,
      three out of four SMs infected with subtype 5 show a significant depletion of
      CD4+ T cells. The fact that virus replication in SMs infected with subtype 5 is
      similar to that in SMs infected with other SIV(smm) subtypes suggests that the
      subtype 5-associated CD4+ T-cell depletion is unlikely to simply reflect higher
      levels of virus-mediated direct killing of CD4+ T-cells. Taken together, this
      systematic analysis of the subtype-specific features of SIV(smm) infection in
      natural SM hosts identifies subtype-specific differences in the pathogenicity of
      SIV(smm) infection.

PMID- 17507490
TI  - Simian varicella virus expresses a latency-associated transcript that is
      antisense to open reading frame 61 (ICP0) mRNA in neural ganglia of latently
      infected monkeys.
AB  - Simian varicella virus (SVV) and varicella-zoster virus (VZV) are closely related
      alphaherpesviruses that cause varicella (chickenpox) in nonhuman primates and
      humans, respectively. After resolution of the primary disease, SVV and VZV
      establish latent infection of neural ganglia and may later reactivate to cause a
      secondary disease (herpes zoster). This study investigated SVV gene expression in
      neural ganglia derived from latently infected vervet monkeys. SVV transcripts
      were detected in neural ganglia, but not in liver or lung tissues, of latently
      infected animals. A transcript mapping to open reading frame (ORF) 61 (herpes
      simplex virus type 1 [HSV-1] ICP0 homolog) was consistently detected in latently
      infected trigeminal, cervical, and lumbar ganglia by reverse transcriptase PCR.
      Further analysis confirmed that this SVV latency-associated transcript (LAT) was
      oriented antisense to the gene 61 mRNA. SVV ORF 21 transcripts were also detected
      in 42% of neural ganglia during latency. In contrast, SVV ORF 28, 29, 31, 62, and
      63 transcripts were not detected in ganglia, liver, or lung tissues of latently
      infected animals. The results demonstrate that viral gene expression is limited
      during SVV latency and that a LAT antisense to an ICP0 homolog is expressed. In
      this regard, SVV gene expression during latency is similar to that of HSV-1 and
      other neurotropic animal alphaherpesviruses but differs from that reported for
      VZV.

PMID- 17507492
TI  - DNA immunization using highly conserved murine cytomegalovirus genes encoding
      homologs of human cytomegalovirus UL54 (DNA polymerase) and UL105 (helicase)
      elicits strong CD8 T-cell responses and is protective against systemic challenge.
AB  - Human cytomegalovirus (HCMV) establishes a lifelong infection with the potential
      for reinfection or viral transmission even in the presence of strong and diverse
      CD8 T-lymphocyte responses. This suggests that the CMVs skew the host T-cell
      response in order to favor viral persistence. In this study, we hypothesized that
      the essential, nonstructural proteins that are highly conserved among the CMVs
      may represent a novel class of T-cell targets for vaccine-mediated protection due
      to their requirements for expression and sequence stability, but that the
      observed subdominance of these antigens in the CMV-infected host results from the
      virus limiting the T-cell responses to otherwise-protective specificities. We
      found that DNA immunization of mice with the murine CMV (MCMV) homologs of HCMV
      DNA polymerase (M54) or helicase (M105) was protective against virus replication
      in the spleen following systemic challenge, with the protection level elicited by
      the M54 DNA being comparable to that of DNA expressing the immunodominant IE1
      (pp89). Intracellular gamma interferon staining of CD8 T cells from mice
      immunized with either the M54 or M105 DNAs showed strong primary responses that
      recalled rapidly after viral challenge. M54- and M105-specific CD8 T cells were
      detected after the primary MCMV infection, but their levels were not consistently
      above the background level. The conserved, essential proteins of the CMVs thus
      represent a novel class of CD8 T-cell targets that may contribute to a successful
      HCMV vaccine strategy.

PMID- 17507491
TI  - Direct ex vivo analyses of HLA-DR1 transgenic mice reveal an exceptionally broad
      pattern of immunodominance in the primary HLA-DR1-restricted CD4 T-cell response
      to influenza virus hemagglutinin.
AB  - The recent threat of an avian influenza pandemic has generated significant
      interest in enhancing our understanding of the events that dictate protective
      immunity to influenza and in generating vaccines that can induce heterosubtypic
      immunity. Although antigen-specific CD4 T cells are known to play a key role in
      protective immunity to influenza through the provision of help to B cells and CD8
      T cells, little is known about the specificity and diversity of CD4 T cells
      elicited after infection, particularly those elicited in humans. In this study,
      we used HLA-DR transgenic mice to directly and comprehensively identify the
      specificities of hemagglutinin (HA)-specific CD4 T cells restricted to a human
      class II molecule that were elicited following intranasal infection with a strain
      of influenza virus that has been endemic in U.S. human populations for the last
      decade. Our results reveal a surprising degree of diversity among influenza virus
      specific CD4 T cells. As many as 30 different peptides, spanning the entire HA
      protein, were recognized by CD4 T cells, including epitopes genetically conserved
      among H1, H2, and H5 influenza A viruses. We also compared three widely used
      major histocompatibility class II algorithms to predict HLA-DR binding peptides
      and found these as yet inadequate for identifying influenza virus-derived
      epitopes. The results of these studies offer key insights into the spectrum of
      peptides recognized by HLA-DR-restricted CD4 T cells that may be the focus of
      immune responses to infection or to experimental or clinical vaccines in humans.

PMID- 17507493
TI  - Herpes simplex virus type 1 cytoplasmic envelopment requires functional Vps4.
AB  - The assembly and egress of herpesviruses are complex processes that require the
      budding of viral nucleocapsids into the lumen of cytoplasmic compartments to form
      mature infectious virus. This envelopment stage shares many characteristics with
      the formation of luminal vesicles in multivesicular endosomes. Through expression
      of dominant-negative Vps4, an enzyme that is essential for the formation of
      luminal vesicles in multivesicular endosomes, we now show that Vps4 function is
      required for the cytoplasmic envelopment of herpes simplex virus type 1. This is
      the first example of a large enveloped DNA virus engaging the multivesicular
      endosome sorting machinery to enable infectious virus production.

PMID- 17507494
TI  - Thermolabilizing pseudoreversions in reovirus outer-capsid protein micro 1 rescue
      the entry defect conferred by a thermostabilizing mutation.
AB  - Heat-resistant mutants selected from infectious subvirion particles of mammalian
      reoviruses have determinative mutations in the major outer-capsid protein micro
      1. Here we report the isolation and characterization of intragenic
      pseudoreversions of one such thermostabilizing mutation. From a plaque that had
      survived heat selection, a number of viruses with one shared mutation but
      different second-site mutations were isolated. The effect of the shared mutation
      alone or in combination with second-site mutations was examined using recoating
      genetics. The shared mutation, D371A, was found to confer (i) substantial
      thermostability, (ii) an infectivity defect that followed attachment but preceded
      viral protein synthesis, and (iii) resistance to micro 1 rearrangement in vitro,
      with an associated failure to lyse red blood cells. Three different second-site
      mutations were individually tested in combination with D371A and found to wholly
      or partially revert these phenotypes. Furthermore, when tested alone in recoated
      particles, each of these three second-site mutations conferred demonstrable
      thermolability. This and other evidence suggest that pseudoreversion of micro 1
      based thermostabilization can occur by a general mechanism of micro 1-based
      thermolabilization, not requiring a specific compensatory mutation. The
      thermostabilizing mutation D371A as well as 9 of the 10 identified second-site
      mutations are located near contact regions between micro 1 trimers in the
      reovirus outer capsid. The availability of both thermostabilizing and
      thermolabilizing mutations in micro 1 should aid in defining the conformational
      rearrangements and mechanisms involved in membrane penetration during cell entry
      by this structurally complex nonenveloped animal virus.

PMID- 17507495
TI  - Type III interferon (IFN) induces a type I IFN-like response in a restricted
      subset of cells through signaling pathways involving both the Jak-STAT pathway
      and the mitogen-activated protein kinases.
AB  - Type III interferon (IFN) is a novel member of the interferon family. Type III
      IFN utilizes a receptor complex different from that of type I IFN, but both types
      of IFN induce STAT1, STAT2, and STAT3 activation. Here we describe a detailed
      comparison of signal transduction initiated by type I and type III IFN. Gene
      expression array analysis showed that IFN types I and III induced a similar
      subset of genes. In particular, no genes were induced uniquely by type III IFN.
      Next, we used chromatin immunoprecipitation (ChIP) analysis to investigate the
      promoter activation by types I and III IFN. The ChIP assays demonstrated that
      stimulation of cells with both type I and type III IFN resulted in the
      recruitment of ISGF3 transcription factor components to the promoter region of
      responsive genes and in an increase of polymerase II loading and histone
      acetylation. Whereas IFN type I signaling was observed for a broad spectrum of
      cell lines, type III IFN signaling was more restricted. The lack of IFN type III
      signaling was correlated with a low expression of the IL28Ra component of the IFN
      type III receptor, and IL28Ra overexpression was sufficient to restore IFN type
      III signaling. We also tested the activation of mitogen-activated protein (MAP)
      kinases by type III IFN and found that type III IFN relies strongly upon both p38
      and JNK MAP kinases for gene induction.

PMID- 17507496
TI  - Periaqueductal gray metabotropic glutamate receptor subtype 7 and 8 mediate
      opposite effects on amino acid release, rostral ventromedial medulla cell
      activities, and thermal nociception.
AB  - The current study has investigated the involvement of periaqueductal gray (PAG)
      metabotropic glutamate subtype 7 and 8 receptors (mGluR(7) and mGluR(8)) in
      modulating rostral ventromedial medulla (RVM) ongoing and tail flick-related on
      and off cell activities. Our study has also investigated the role of PAG mGluR(7)
      on thermoceptive threshold and PAG glutamate and GABA release. Intra
      ventrolateral PAG (S)-3,4-dicarboxyphenylglycine [(S)-3,4-DCPG (2 and 4
      nmol/rat)] or N,N(I)-dibenzhydrylethane-1,2-diamin dihydrochloride (AMN082, (1
      and 2 nmol/rat), selective mGluR(8) and mGluR(7) agonists, respectively, caused
      opposite effects on the ongoing RVM on and off cell activities. Tail flick
      latency was increased or decreased by (S)-3,4-DCPG or AMN082 (2 nmol/rat),
      respectively. (S)-3,4-DCPG reduced the pause and delayed the onset of the off
      cell pause. Conversely, AMN082 increased the pause and shortened the onset of off
      cell pause. (S)-3,4-DCPG or AMN082 did not change the tail flick-induced onset of
      on-cell peak firing. The tail flick latency and its related electrophysiological
      effects induced by (S)-3,4-DCPG or AMN082 were prevented by (RS)-alpha
      methylserine-o-phosphate (100 nmol/rat), a group III mGluR antagonist. Intra
      ventrolateral PAG perfusion with AMN082 (10 and 25 microM), decreased
      thermoceptive thresholds and glutamate extracellular levels. A decrease in GABA
      release was also observed. These results show that stimulation of PAG mGluR(8) or
      mGluR(7) could either relieve or worsen pain perception. The opposite effects on
      pain behavior correlate with the opposite roles played by mGluR(7) and mGluR(8)
      on glutamate and GABA release and the ongoing and tail flick-related activities
      of the RVM on and off cells.

PMID- 17507498
TI  - Representation of stereoscopic depth based on relative disparity in macaque area
      V4.
AB  - Stereoscopic vision is characterized by greater visual acuity when a background
      feature serves as a reference. When a reference is present, the perceived depth
      of an object is predominantly dependent on this reference. Neural representations
      of stereoscopic depth are expected to have a relative frame of reference. The
      conversion of absolute disparity encoded in area V1 to relative disparity begins
      in area V2, although the information encoded in this area appears to be
      insufficient for stereopsis. This study examines whether relative disparity is
      encoded in a higher cortical area. We recorded the responses of V4 neurons from
      macaque monkeys to various combinations of the absolute disparities of two
      features: the center patch and surrounding annulus of a dynamic random-dot
      stereogram. We analyzed the effects of the disparity of the surrounding annulus
      on the tuning for the disparity of the center patch; the tuning curves of
      relative-disparity-selective neurons for disparities of the center patch should
      shift with changes in the disparity of the surrounding annulus. Most V4 tuning
      curves exhibited significant shifts. The magnitudes of the shifts were larger
      than those reported for V2 neurons and smaller than that expected for an ideal
      relative-disparity-selective cell. No correlation was found between the shift
      magnitude and the degree of size suppression, suggesting that the two phenomena
      are not the result of a common mechanism. Our results suggest that the coding of
      relative disparity advances as information flows along the cortical pathway that
      includes areas V2 and V4.

PMID- 17507497
TI  - Lidocaine promotes the trafficking and functional expression of Na(v)1.8 sodium
      channels in mammalian cells.
AB  - Nociceptive neurons of the dorsal root ganglion (DRG) express a combination of
      rapidly gating TTX-sensitive and slowly gating TTX-resistant Na currents, and the
      channels that produce these currents have been cloned. The Na(v)1.7 and Na(v)1.8
      channels encode for the rapidly inactivating TTX-sensitive and slowly
      inactivating TTX-resistant Na currents, respectively. Although the Na(v)1.7
      channel expresses well in cultured mammalian cell lines, attempts to express the
      Na(v)1.8 channel using similar approaches has been met with limited success. The
      inability to heterologously express Na(v)1.8 has hampered detailed
      characterization of the biophysical properties and pharmacology of these
      channels. In this study, we investigated the determinants of Na(v)1.8 expression
      in tsA201 cells, a transformed variant of HEK293 cells, using a combination of
      biochemistry, immunochemistry, and electrophysiology. Our data indicate that the
      unusually low expression levels of Na(v)1.8 in tsA201 cells results from a
      trafficking defect that traps the channel protein in the endoplasmic reticulum.
      Incubating the cultured cells with the local anesthetic lidocaine dramatically
      enhanced the cell surface expression of functional Na(v)1.8 channels. The
      biophysical properties of the heterologously expressed Na(v)1.8 channel are
      similar but not identical to those of the TTX-resistant Na current of native DRG
      neurons, recorded under similar conditions. Our data indicate that the lidocaine
      acts as a molecular chaperone that promotes efficient trafficking and increased
      cell surface expression of Na(v)1.8 channels.

PMID- 17507499
TI  - Membrane properties and firing patterns of inferior colliculus neurons: an in
      vivo patch-clamp study in rodents.
AB  - The inferior colliculus (IC) is a large auditory nucleus in the midbrain, which
      is a nearly obligatory relay center for ascending auditory projections. We made
      in vivo whole cell patch-clamp recordings of IC cells in young-adult anesthetized
      C57/Bl6 mice and Wistar rats to characterize their membrane properties and
      spontaneous inputs. We observed spikelets in both rat (18%) and mouse (13%) IC
      neurons, suggesting that IC neurons may be connected by electrical synapses. In
      many cells, spontaneous postsynaptic potentials were sufficiently large to
      contribute to spike irregularity. Cells differed considerably in the number of
      simultaneous spontaneous postsynaptic potentials that would be needed to trigger
      an action potential. Depolarizing and hyperpolarizing current injections showed
      six different types of firing patterns: buildup, accelerating, burst-onset, burst
      sustained, sustained, and accommodating. Their relative frequencies were similar
      in both species. In mice, about half of the cells showed a clear depolarizing
      sag, suggesting that they have the hyperpolarization-activated current I(h). This
      sag was observed more often in burst and in accommodating cells than in buildup,
      accelerating, or sustained neurons. Cells with I(h) had a significantly more
      depolarized resting membrane potential. They were more likely to fire rebound
      spikes and generally showed long-lasting afterhyperpolarizations following long
      depolarizations. We therefore suggest a separate functional role for I(h).

PMID- 17507500
TI  - GIRK channels as a target for SSRIs. Focus on "reduced 5-HT1A- and GABAB receptor
      function in dorsal raphe neurons upon chronic fluoxetine treatment of socially
      stressed rats".

PMID- 17507501
TI  - Synaptic transmission at the calyx of Held under in vivo like activity levels.
AB  - One of the hallmarks of auditory neurons in vivo is spontaneous activity that
      occurs even in the absence of any sensory stimuli. Sound-evoked bursts of
      discharges are thus embedded within this background of random firing. The calyx
      of Held synapse in the medial nucleus of the trapezoid body (MNTB) has been
      characterized in vitro as a fast relay that reliably fires at high stimulus
      frequencies (< or =800 Hz). However, inherently due to the preparation method,
      spontaneous activity is absent in studies using brain stem slices. Here we first
      determine in vivo spontaneous firing rates of MNTB principal cells from Mongolian
      gerbils and then reintroduce this random firing to in vitro gerbil brain stem
      synapses at near-physiological temperature. After conditioning synapses with
      afferent fiber stimulation for 2 min at Poisson averaged rates of 20, 40, and 60
      Hz, we observed a number of differences in the properties of synaptic
      transmission between conditioned and unconditioned synapses. Foremost, we
      observed reduced steady-state EPSC amplitudes that depressed even further during
      an embedded short-stimulation train of 100, 300, or 600 Hz (a protocol that thus
      simulates in vitro what probably occurs at the in vivo MNTB after a short sound
      stimulus in a silent background). Accordingly, current-clamp, dynamic-clamp, and
      loose-patch recordings revealed a number of action potential failures at the
      postsynaptic cell during high-frequency-stimulation trains, although the initial
      onset of evoked activity was still transmitted with higher fidelity. We thus
      propose that some in vivo auditory synapses are in a tonic state of reduced EPSC
      amplitudes as a consequence of high spontaneous spiking and this in vivo-like
      conditioning has important consequences for the encoding of signals throughout
      the auditory pathway.

PMID- 17507502
TI  - Local and intersegmental interactions of coordinating neurons and local circuits
      in the swimmeret system.
AB  - During forward swimming, periodic movements of swimmerets on different segments
      of the crayfish abdomen progress from back to front with the same period.
      Information encoded as bursts of spikes by coordinating neurons in each segmental
      ganglion is necessary for this coherent organization. This information is
      conducted to targets in other ganglia. When an individual coordinating neuron is
      stimulated at different phases in the system's cycle of activity, the timing of
      motor output from other ganglia may be altered. In models of this coordinating
      circuit, we assumed that each coordinating neuron encodes information about the
      state of the local pattern-generating circuit in its home ganglion but is not
      part of that local circuit. We tested this assumption by stimulating individual
      coordinating neurons of two kinds -- ASC(E) and DSC -- at different phases under
      two conditions: with the target ganglion functional, and with the target ganglion
      silenced. Blocking a DSC neuron's target ganglion did not alter its negligible
      influence on the output from its home ganglion; the phase-response curves (PRC)
      remained flat. Blocking an ASC(E) neuron's target ganglion significantly affected
      its influence on the output from its home ganglion. We had predicted that
      ASC(E)'s modest phase-dependent influence would disappear with the target
      silenced, but instead the amplitude of the PRCs increased significantly. Thus we
      have two different results: DSC neurons conformed to prediction based on the
      models' assumptions, but ASC(E) neurons showed an unexpected property, one that
      is partially masked when the bidirectional flow of information between
      neighboring ganglia is operating normally.

PMID- 17507503
TI  - Functional connectivity between secondary and primary motor areas underlying hand
      foot coordination.
AB  - Coincident hand and foot movements are more reliably performed in the same
      direction than in opposite directions. Using transcranial magnetic stimulation
      (TMS) to assess motor cortex function, we examined the physiological basis of
      these movements across three novel experiments. Experiment 1 demonstrated that
      upper limb corticomotor excitability changed in a way that facilitated
      isodirectional movements of the hand and foot, during phasic and isometric muscle
      activation conditions. Experiment 2 demonstrated that motor cortex inhibition was
      modified with active, but not passive, foot movement in a manner that facilitated
      hand movement in the direction of foot movement. Together, these findings
      demonstrate that the coupling between motor representations within motor cortex
      is activity dependent. Because there are no known connections between hand and
      foot areas within primary motor cortex, experiment 3 used a dual-coil paired
      pulse TMS protocol to examine functional connectivity between secondary and
      primary motor areas during active ankle dorsiflexion and plantarflexion. Dorsal
      premotor cortex (PMd) and supplementary motor area (SMA) conditioning, but not
      ventral premotor cortex (PMv) conditioning, produced distinct phases of task
      dependent modulation of excitability of forearm representations within primary
      motor cortex (M1). Networks involving PMd-M1 facilitate isodirectional movements
      of hand and foot, whereas networks involving SMA-M1 facilitate corticomotor
      pathways nonspecifically, which may help to stabilize posture during interlimb
      coordination. These results may have implications for targeted
      neurorehabilitation after stroke.

PMID- 17507504
TI  - Sensory prediction errors drive cerebellum-dependent adaptation of reaching.
AB  - The cerebellum is an essential part of the neural network involved in adapting
      goal-directed arm movements. This adaptation might rely on two distinct signals:
      a sensory prediction error or a motor correction. Sensory prediction errors occur
      when an initial motor command is generated but the predicted sensory consequences
      do not match the observed values. In some tasks, these sensory errors are
      monitored and result in on-line corrective motor output as the movement
      progresses. Here we asked whether cerebellum-dependent adaptation of reaching
      relies on sensory or on-line motor corrections. Healthy controls and people with
      hereditary cerebellar ataxia reached during a visuomotor perturbation in two
      conditions: "shooting" movements without on-line corrections and "pointing"
      movements that allowed for on-line corrections. Sensory (i.e., visual) errors
      were available in both conditions. Results showed that the addition of motor
      corrections did not influence adaptation in control subjects, suggesting that
      only sensory errors were needed for learning. Cerebellar subjects were comparably
      impaired in both adaptation conditions relative to controls, despite abnormal and
      inconsistent on-line motor correction. Specifically, poor on-line motor
      corrections were unrelated to cerebellar subjects' adaptation deficit (i.e.,
      adaptation did not worsen), further suggesting that only sensory prediction
      errors influence this process. Therefore adaptation to visuomotor perturbations
      depends on the cerebellum and is driven by the mismatch between predicted and
      actual sensory outcome of motor commands.

PMID- 17507505
TI  - Comparison of responses of neurons in the mouse inferior colliculus to current
      injections, tones of different durations, and sinusoidal amplitude-modulated
      tones.
AB  - We made in vivo whole cell patch-clamp recordings from the inferior colliculus of
      young-adult, anesthetized C57/Bl6 mice to compare the responses to constant
      current injections with the responses to tones of different duration or to
      sinusoidal amplitude-modulated (SAM) tones. We observed that voltage-dependent
      ion channels contributed in several ways to the response to tones. A sustained
      response to long tones was observed only in cells showing little accommodation
      during current injection. Cells showing burst-onset firing during current
      injection showed a small response to SAM tones, whereas burst-sustained cells
      showed a good response to SAM tones. The hyperpolarization-activated nonselective
      cation channel I(h) had a special role in shaping the responses: I(h) was
      associated with an increased excitability, with chopper and pauser responses, and
      with an afterhyperpolarization following tones. Synaptic properties were more
      important in determining the responses to tones of different durations. A short
      latency inhibitory response appeared to contribute to the long-pass response in
      some cells and short-pass and band-pass neurons were characterized by their slow
      recovery from synaptic adaptation. Cells that recovered slowly from synaptic
      adaptation showed a relatively small response to SAM tones. Our results show an
      important role for both intrinsic membrane properties -- most notably the
      presence of I(h) and the extent of accommodation -- and synaptic adaptation in
      shaping the response to tones in the inferior colliculus.

PMID- 17507506
TI  - Effects of inhibitory gain and conductance fluctuations in a simple model for
      contrast-invariant orientation tuning in cat V1.
AB  - The origin of orientation selectivity in primary visual cortex (V1) is a model
      problem for understanding cerebral cortical circuitry. A key constraint is that
      orientation tuning width is invariant under changes in stimulus contrast. We have
      previously shown that this can arise from the combination of feedforward lateral
      geniculate nucleus (LGN) input and an orientation-untuned component of
      feedforward inhibition that dominates excitation. However, these models did not
      include the large background voltage noise observed in vivo. Here, we include
      this noise and examine a simple model of cat V1 response. Constraining our
      simulations to fit physiological data, our single model parameter is the strength
      of feedforward inhibition relative to LGN excitation. With physiological noise,
      the contrast invariance of orientation tuning depends little on inhibition level,
      although very weak or very strong inhibition leads to weak broadening or
      sharpening, respectively, of tuning with contrast. For any inhibition level, an
      alternative measure of orientation tuning -- the circular variance -- decreases
      with contrast as observed experimentally. These results arise primarily because
      the voltage noise causes large inputs to be much more strongly amplified than
      small ones in evoking spiking responses, relatively suppressing responses to
      nonpreferred stimuli. However, inhibition comparable to or stronger than
      excitation appears necessary to suppress spiking responses to nonpreferred
      orientations to the extent seen in vivo and to allow the emergence of a tuned
      mean voltage response. These two response properties provide the strongest
      constraints on model details. Antiphase inhibition from inhibitory simple cells,
      and not just untuned inhibition from inhibitory complex cells, appears necessary
      to fully explain these aspects of cortical orientation tuning.

PMID- 17507508
TI  - Endogenous D-serine contributes to NMDA-receptor-mediated light-evoked responses
      in the vertebrate retina.
AB  - We have combined electrophysiology and chemical separation and measurement
      techniques with capillary electrophoresis (CE) to evaluate the role of endogenous
      d-serine as an NMDA receptor (NMDAR) coagonist in the salamander retina.
      Electrophysiological experiments were carried out using whole cell recordings
      from retinal ganglion cells and extracellular recordings of the proximal negative
      response (PNR), while bath applying two D-serine degrading enzymes, including d
      amino acid oxidase (DAAO) and D-serine deaminase (DsdA). The addition of either
      enzyme resulted in a significant and rapid decline in the light-evoked responses
      observed in ganglion cell and PNR recordings. The addition of exogenous D-serine
      in the presence of the enzymes restored the light-evoked responses to the control
      or supracontrol amplitudes. Heat-inactivated enzymes had no effect on the light
      responses and blocking NMDARs with AP7 eliminated the suppressive influence of
      the enzymes as well as the response enhancement normally associated with
      exogenous d-serine application. CE was used to separate amino acid racemates and
      to study the selectivity of DAAO and DsdA against D-serine and glycine. Both
      enzymes showed high selectivity for D-serine without significant effects on
      glycine. Our results strongly support the concept that endogenous D-serine plays
      an essential role as a coagonist for NMDARs, allowing them to contribute to the
      light-evoked responses of retinal ganglion cells. Furthermore under our
      experimental conditions, these coagonist sites are not saturated so that
      modulation of NMDAR sensitivity can be achieved with further modulaton of d
      serine.

PMID- 17507507
TI  - Selective delay activity in the medial prefrontal cortex of the rat: contribution
      of sensorimotor information and contingency.
AB  - The medial prefrontal cortex (mPFC) plays a critical role in the organization of
      goal-directed behaviors and in the learning of reinforcement contingencies. Given
      these observations, it was hypothesized that mPFC neurons may store associations
      between sequentially paired stimuli when both stimuli contribute to the
      prediction of reward. To test this hypothesis, neural-ensemble spiking activity
      was recorded as rats performed a paired-associate discrimination task. Rats were
      trained to associate sequentially presented stimuli with probabilistic reward. In
      one condition, both elements of the stimulus sequence provided information about
      reward delivery. In another condition, only the first stimulus contributed to the
      prediction. As hypothesized, stimulus-selective, prospective delay activity was
      observed during sequences in which both elements contributed to the prediction of
      reward. Unexpectedly, selective delay responses were associated with slight
      variations in head position and thus not necessarily generated by intrinsic
      mnemonic processes. Interestingly, the sensitivity of neurons to head position
      was greatest during intervals when reward delivery was certain. These results
      suggest that a significant portion of delay activity in the rat mPFC reflects
      task-relevant sensorimotor activity, possibly related to enhancing stimulus
      detection, rather than stimulus-stimulus associations. These observations agree
      with recent evidence that suggests that prefrontal neurons are particularly
      responsive during the performance of action sequences related to the acquisition
      of reward. These results also indicate that considerable attention must be given
      to the monitoring and analysis of sensorimotor variables during delay tasks
      because slight changes in position can produce activity in the mPFC that
      erroneously appears to be driven by intrinsic mechanisms.

PMID- 17507509
TI  - Evaluation of the colorimetric VITEK 2 card for identification of gram-negative
      nonfermentative rods: comparison to 16S rRNA gene sequencing.
AB  - Ninety strains of a collection of well-identified clinical isolates of gram
      negative nonfermentative rods collected over a period of 5 years were evaluated
      using the new colorimetric VITEK 2 card. The VITEK 2 colorimetric system
      identified 53 (59%) of the isolates to the species level and 9 (10%) to the genus
      level; 28 (31%) isolates were misidentified. An algorithm combining the
      colorimetric VITEK 2 card and 16S rRNA gene sequencing for adequate
      identification of gram-negative nonfermentative rods was developed. According to
      this algorithm, any identification by the colorimetric VITEK 2 card other than
      Achromobacter xylosoxidans, Acinetobacter sp., Burkholderia cepacia complex,
      Pseudomonas aeruginosa, and Stenotrophomonas maltophilia should be subjected to
      16S rRNA gene sequencing when accurate identification of nonfermentative rods is
      of concern.

PMID- 17507510
TI  - Simultaneous detection and high-throughput identification of a panel of RNA
      viruses causing respiratory tract infections.
AB  - Clinical presentations for viral respiratory tract infections are often
      nonspecific, and a rapid, high-throughput laboratory technique that can detect a
      panel of common viral pathogens is clinically desirable. We evaluated two
      multiplex reverse transcription-PCR (RT-PCR) products coupled with microarray
      based systems for simultaneous detection of common respiratory tract viral
      pathogens. The NGEN respiratory virus analyte-specific assay (Nanogen, San Diego,
      CA) detects influenza A virus (Flu-A) and Flu-B, parainfluenza virus 1 (PIV-1),
      PIV-2, and PIV-3, and respiratory syncytial virus (RSV), while the ResPlex II
      assay (Genaco Biomedical Products, Inc., Huntsville, AL) detects Flu-A, Flu-B,
      PIV-1, PIV-2, PIV-3, PIV-4, RSV, human metapneumovirus (hMPV), rhinoviruses
      (RhVs), enteroviruses (EnVs), and severe acute respiratory syndrome (SARS)
      coronavirus (CoV). A total of 360 frozen respiratory specimens collected for a
      full year were tested, and results were compared to those obtained with a
      combined reference standard of cell culture and monoplex real-time TaqMan RT-PCR
      assays. NGEN and ResPlex II gave comparable sensitivities for Flu-A (82.8 to
      86.2%), Flu-B (90.0 to 100.0%), PIV-1 (87.5 to 93.8%), PIV-3 (66.7 to 72.2%), and
      RSV (63.3 to 73.3%); both assays achieved excellent specificities (99.1 to
      100.0%) for these five common viruses. The ResPlex II assay detected hMPV in 13
      (3.6%) specimens, with a sensitivity of 80.0% and specificity of 99.7%. The
      ResPlex II assay also differentiated RSV-A and RSV-B and gave positive results
      for RhV and EnV in 31 (8.6%) and 19 (5.3%) specimens, respectively. PIV-2, PIV-4,
      and SARS CoV were not detected in the specimens tested. The two systems can
      process 80 (NGEN) and 96 (ResPlex II) tests per run, with a hands-on time of
      approximately 60 min and test turnaround times of 6 h (ResPlex II) and 9 h
      (NGEN). Multiple-panel testing detected an additional unsuspected 9 (3.4%) PIV-1
      and 10 (3.7%) PIV-3 infections. While test sensitivities for RSV and PIV-3 need
      improvement, both the NGEN and ResPlex II assays provide user-friendly and high
      throughput tools for simultaneous detection and identification of a panel of
      common respiratory viral pathogens in a single test format. The multiplex
      approach enhances diagnosis through detection of respiratory viral etiologic
      agents in cases in which the presence of the agent was not suspected and a test
      was not ordered by the clinicians.

PMID- 17507511
TI  - Contribution of polymorphisms in ankA, gltA, and groESL in defining genetic
      variants of Anaplasma phagocytophilum.
AB  - Analysis of several nucleotide polymorphisms in polymorphic genes (ankA, gltA,
      and groESL) from 16S rRNA gene-based genetic variants of Anaplasma
      phagocytophilum from dogs in the western United States defined at least two sets
      of multigene polymorphisms to further characterize these variants. The multigene
      polymorphism approach holds promise for development of a genotyping scheme for
      this important pathogen.

PMID- 17507512
TI  - Meningitis due to Gemella haemolysans in a pediatric case.
AB  - Gemella haemolysans is a rare pathogen in cases of bacterial meningitis. We
      present a case of meningitis due to G. haemolysans in a 17-month-old boy. This is
      the first reported case of Gemella meningitis in a child. The patient completely
      recovered following intravenous therapy with linezolid and chloramphenicol.

PMID- 17507513
TI  - Increased detection of respiratory syncytial virus, influenza viruses,
      parainfluenza viruses, and adenoviruses with real-time PCR in samples from
      patients with respiratory symptoms.
AB  - Respiratory samples (n = 267) from hospitalized patients with respiratory
      symptoms were tested by real-time PCR, viral culture, and direct
      immunofluorescence for respiratory syncytial virus, influenza virus,
      parainfluenza viruses, and adenoviruses. Compared with conventional diagnostic
      tests, real-time PCR increased the diagnostic yields for these viruses from 24%
      to 43% and from 3.5% to 36% for children and adults, respectively.

PMID- 17507514
TI  - PCR-restriction fragment length polymorphism analysis of Campylobacter jejuni
      genes involved in lipooligosaccharide biosynthesis identifies putative molecular
      markers for Guillain-Barre syndrome.
AB  - Molecular mimicry of Campylobacter jejuni lipooligosaccharides (LOS) by
      gangliosides in peripheral nerve tissue probably triggers the Guillain-Barre
      syndrome due to the induction of cross-reactive antibodies. PCR-restriction
      fragment length polymorphism analysis of C. jejuni genes involved in the
      biosynthesis of LOS demonstrated that specific genes were associated with the
      expression of ganglioside mimics and the development of neuropathy.

PMID- 17507515
TI  - First insight into the population structure of Mycobacterium tuberculosis in
      Saudi Arabia.
AB  - This study constitutes a first attempt to describe the genetic population
      structure and drug resistance of the tubercle bacilli circulating in Saudi
      Arabia. A total of 1,505 clinical isolates of M. tuberculosis, isolated between
      2002 and 2005 from seven regions of Saudi Arabia, were studied. The sample
      studied showed a male-to-female sex ratio of 1.27, with half of the cases among
      foreign-born individuals and 47% within the 21- to 40-year-old age group; a total
      resistance rate of 19.7%; and multiple drug resistance of 4.5%. Upon
      spoligotyping, a total of 387 individual patterns were obtained (clustering rate,
      86.4%; 182 clusters containing between 2 and 130 isolates per cluster). A total
      of 94% of the strains matched the spoligotype patterns in an international
      database. Nearly 81% of the isolates in this study belonged to established
      phylogeographic clades: Central Asian (CAS), 22.5%; ill-defined T clade, 19.5%;
      East African-Indian (EAI), 13.5%; Haarlem, 7.5%; Latin American-Mediterranean,
      7.2%; Beijing, 4.4%; Manu, 2.7%; X, 0.9%; and Bovis, 0.9%. Two clonal complexes
      with unique spoligotyping signatures (octal codes 703777707770371 and
      467777377413771) specific to Saudi Arabia were identified. These belonged to the
      CAS and EAI clades, respectively, as confirmed upon secondary typing using
      mycobacterial interspersed repetitive units (MIRUs). The results obtained
      underline the predominance of historic clones of principal genetic group 1, which
      are responsible for roughly 45% of all tuberculosis cases in Saudi Arabia. The
      high rate of clustering observed might be an indication of rapid ongoing
      transmission within certain communities and/or subpopulations in Saudi Arabia;
      nonetheless, spoligotyping is known to overestimate clustering, and only a
      systematic second-line typing, such as MIRUs, coupled with a better tuberculosis
      registry and epidemiological investigations would allow us to know the exact rate
      of ongoing transmission and associated risk factors in Saudi Arabia.

PMID- 17507516
TI  - Performance of the HerpeSelect (Focus) and Kalon enzyme-linked immunosorbent
      assays for detection of antibodies against herpes simplex virus type 2 by use of
      monoclonal antibody-blocking enzyme immunoassay and clinicovirological reference
      standards in Brazil.
AB  - A total of 586 serum samples were used to evaluate the performance of type
      specific herpes simplex virus type 2 (HSV-2) commercial enzyme-linked
      immunosorbent assays (ELISAs) by using the monoclonal antibody-blocking enzyme
      immunoassay (MAb-EIA) and a clinicovirological panel as reference standards. The
      Kalon and HerpeSelect ELISAs had similar sensitivities (93.5% and 93.8% compared
      with the results obtained by MAb-EIA, respectively, and 100% for both ELISAs
      compared with the results obtained with a clinicovirological panel). The Kalon
      ELISA had a higher specificity (96.5% and 96.8% compared with the results
      obtained by MAb-EIA and with a clinicovirological panel, respectively) than the
      HerpeSelect ELISA (86.9% and 94% compared with the results obtained by MAb-EIA
      and with a clinicovirological panel, respectively). A higher cutoff significantly
      improved the specificity of the HerpeSelect ELISA.

PMID- 17507517
TI  - Rare case of Nocardia asteroides pericarditis in a human immunodeficiency virus
      infected patient.
AB  - Nocardia asteroides was isolated after prolonged culture from the pericardial
      fluid of a human immunodeficiency virus-infected patient. The lengthy duration
      required for culture growth and identification of this N. asteroides isolate
      affected both initial therapeutic decisions and patient management. A proposed
      algorithm for the microbiological workup of pericardial fluid for possible
      Nocardia spp. is described in an effort to improve the timeliness of results.

PMID- 17507518
TI  - Fatal relapse of a purulent pleurisy caused by Campylobacter fetus subsp. fetus.
AB  - Campylobacter fetus is associated with invasive disease, while other
      Campylobacter species, such as C. coli and C. jejuni, are a common cause of
      bacterial diarrhea. Bacteremia has been well described, but pleurisy remains very
      uncommon. We report the recurrent isolation of a C. fetus subsp. fetus strain
      during two episodes of pleural effusion with a fatal outcome.

PMID- 17507519
TI  - Rapid identification of Staphylococci isolated in clinical microbiology
      laboratories by matrix-assisted laser desorption ionization-time of flight mass
      spectrometry.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF-MS) of intact bacteria yields a reproducible spectrum depending upon
      growth conditions, strain, or species. Using whole viable bacteria we describe
      here the application of MALDI-TOF-MS to the identification of coagulase-negative
      staphylococci (CoNS). Our aim was, once a bacterium has been recognized as
      Micrococcaceae, to identify peaks in the spectrum that can be used to identify
      the species or subspecies. MALDI-TOF-MS was performed using bacteria obtained
      from one isolated colony. One reference strain for each of the 23 clinically
      relevant species or subspecies of Micrococcaceae was selected. For each reference
      strain, the MALDI-TOF-MS profile of 10 colonies obtained from 10 different
      passages was analyzed. For each strain, only peaks that were conserved in the
      spectra of all 10 isolated colonies and with a relative intensity above 0.1 were
      retained, thus leading to a set of 3 to 14 selected peaks per strain. The MALDI
      TOF-MS profile of 196 tested strains was then compared with that of the set of
      selected peaks of each of the 23 reference strains. In all cases the best hit was
      with the set of peaks of the reference strain belonging to the same species as
      that of the tested strain, thus demonstrating that the 23 sets of selected peaks
      can be used as a database for the rapid species identification of CoNS. Similar
      results were obtained using four different growth conditions. Extending this
      strategy to other groups of relevant pathogenic bacteria will allow rapid
      bacterial identification.

PMID- 17507520
TI  - Molecular epidemiology of rotavirus in Central and Southeastern Europe.
AB  - A surveillance network was implemented by the Istituto Superiore di Sanita of
      Rome in collaboration with laboratories of virology in Czech Republic, Slovenia,
      Croatia, Albania, and Bulgaria. About 1,500 rotavirus-positive stool samples were
      collected from children with severe gastroenteritis admitted to hospitals or
      outpatient wards between 2004 and 2006. The G and P genotypes were determined by
      reverse transcription-nested PCR. Significant differences were found in the
      geographical distributions of rotavirus genotypes between countries participating
      in the study. The prevalence of "common" G/P combinations, G1P[8], G3P[8],
      G4P[8], and G2P[4], ranged between 50 and 85%. The G9 genotype, which is emerging
      worldwide, was identified in 2 to 35% of all samples depending on the country.
      Unusual combinations, such as G1 or G4 associated with P[4] or G2 with P[8],
      which may have arisen by reassortment between human strains, were found in
      samples from 3 to 20% of patients. The uncommon genotypes G8P[8] and G10P[6],
      which may have an animal origin, were also identified. Double infections with two
      rotavirus strains were observed in between 1.7 and 14% of cases studied. Our
      findings might implicate challenges for rotavirus vaccine implementation in a
      wide geographic area of the Balkans and Central-Eastern Europe and underscore the
      importance of extensive strain surveillance for success in vaccine development.

PMID- 17507521
TI  - Identification of medically important Candida and non-Candida yeast species by an
      oligonucleotide array.
AB  - The incidence of yeast infections has increased in the recent decades, with
      Candida albicans still being the most common cause of infections. However,
      infections caused by less common yeasts have been widely reported in recent
      years. Based on the internal transcribed spacer 1 (ITS 1) and ITS 2 sequences of
      the rRNA genes, an oligonucleotide array was developed to identify 77 species of
      clinically relevant yeasts belonging to 16 genera. The ITS regions were amplified
      by PCR with a pair of fungus-specific primers, followed by hybridization of the
      digoxigenin-labeled PCR product to a panel of oligonucleotide probes immobilized
      on a nylon membrane for species identification. A collection of 452 yeast strains
      (419 target and 33 nontarget strains) was tested, and a sensitivity of 100% and a
      specificity of 97% were obtained by the array. The detection limit of the array
      was 10 pg of yeast genomic DNA per assay. In conclusion, yeast identification by
      the present method is highly reliable and can be used as an alternative to the
      conventional identification methods. The whole procedure can be finished within
      24 h, starting from isolated colonies.

PMID- 17507522
TI  - Phylogenetic diversity and microsphere array-based genotyping of human pathogenic
      Fusaria, including isolates from the multistate contact lens-associated U.S.
      keratitis outbreaks of 2005 and 2006.
AB  - In 2005 and 2006, outbreaks of Fusarium keratitis associated with soft contact
      lens use occurred in multiple U.S. states and Puerto Rico. A case-control study
      conducted by the Centers for Disease Control and Prevention (CDC) showed a
      significant association between infections and the use of one particular brand of
      lens solution. To characterize the full spectrum of the causal agents involved
      and their potential sources, partial DNA sequences from three loci (RPB2, EF
      1alpha, and nuclear ribosomal rRNA) totaling 3.48 kb were obtained from 91
      corneal and 100 isolates from the patient's environment (e.g., contact lens and
      lens cases). We also sequenced a 1.8-kb region encoding the RNA polymerase II
      second largest subunit (RPB2) from 126 additional pathogenic isolates to better
      understand how the keratitis outbreak isolates fit within the full phylogenetic
      spectrum of clinically important fusaria. These analyses resulted in the most
      robust phylogenetic framework for Fusarium to date. In addition, RPB2 nucleotide
      variation within a 72-isolate panel was used to design 34 allele-specific probes
      to identify representatives of all medically important species complexes and 10
      of the most important human pathogenic Fusarium in a single-well diagnostic
      assay, using flow cytometry and fluorescent microsphere technology. The
      multilocus data revealed that one haplotype from each of the three most common
      species comprised 55% of CDC's corneal and environmental isolates and that the
      corneal isolates comprised 29 haplotypes distributed among 16 species. The high
      degree of phylogenetic diversity represented among the corneal isolates is
      consistent with multiple sources of contamination.

PMID- 17507523
TI  - Enterohepatic Helicobacter species are prevalent in mice from commercial and
      academic institutions in Asia, Europe, and North America.
AB  - The discovery of Helicobacter hepaticus and its role in hepatitis, hepatocellular
      carcinoma, typhlocolitis, and lower-bowel carcinoma in murine colonies was
      followed by the isolation and characterization of other Helicobacter spp.
      involved in enterohepatic disease. Colonization of mouse colonies with members of
      the family Helicobacteriaceae has become an increasing concern for the research
      community. From 2001 to 2005, shipments of selected gift mice from other
      institutions and mice received from specified commercial vendors were screened
      for Helicobacter spp. by culture of cecal tissue. The identities of the isolates
      were confirmed by genus-specific PCR, followed by species-specific PCR and
      restriction fragment length polymorphism analysis. Sequencing of the 16S rRNA
      gene was performed if the species identity was not apparent. The survey included
      79 mice from 34 sources: 2 commercial sources and 16 research sources from the
      United States and 1 commercial source and 15 research sources from Canada,
      Europe, or Asia. Helicobacter spp. were cultured from the ceca of 62 of 79 mice.
      No Helicobacter spp. were found in mice from advertised Helicobacter-free
      production areas from two U.S. vendors. Multiple Helicobacter spp. were found in
      mice from one vendor's acknowledged Helicobacter-infected production area. The
      European commercial vendor had mice infected with novel Helicobacter sp. strain
      MIT 96-1001. Of the U.S. academic institutions, 6 of 16 (37%) had mice infected
      with Helicobacter hepaticus; but monoinfection with H. bilis, H. mastomyrinus, H.
      rodentium, and MIT 96-1001 was also encountered, as were mice infected
      simultaneously with two Helicobacter spp. Non-U.S. academic institutions had mice
      that were either monoinfected with H. hepaticus, monoinfected with seven other
      Helicobacter spp., or infected with a combination of Helicobacter spp. This
      survey indicates that 30 of 34 (88%) commercial and academic institutions in
      Canada, Europe, Asia, Australia, and the United States have mouse colonies
      infected with Helicobacter spp. Mice from 20 of the 34 institutions (59%) were
      most commonly colonized with H. hepaticus alone or in combination with other
      Helicobacter spp. These results indicate that a broad range of Helicobacter spp.
      infect mouse research colonies. The potential impact of these organisms on in
      vivo experiments continues to be an important issue for mice being used for
      biomedical research.

PMID- 17507524
TI  - Real-time PCR for determining capsular serotypes of Haemophilus influenzae.
AB  - A two-step real-time PCR assay targeting all six capsulation loci of Haemophilus
      influenzae (i.e., serotypes a to f) was developed and compared with a previously
      published qualitative PCR assay by using 131 H. influenzae clinical isolates.
      There was a 98.5% concordance between the two tests. The sensitivity of detection
      of capsular type-specific reference strains of H. influenzae a to c (10(1)
      CFU/PCR) was higher than that for type e (10(3) CFU/PCR) and types d and f (10(4)
      CFU/PCR), and a broader dynamic range was obtained (5 to 8 log(10) units). No
      cross-reaction was observed with bacteria commonly isolated from the respiratory
      tract. We showed that both PCR assays are more reliable than slide agglutination
      serotyping. The real-time PCR-based assay seems to be an alternative of choice
      for the epidemiological follow-up of H. influenzae invasive infections.

PMID- 17507525
TI  - Analysis of dynamic angle of gait and radiographic features in subjects with
      hallux abducto valgus and hallux limitus.
AB  - BACKGROUND: Hallux abducto valgus and hallux limitus are two commonly encountered
      foot deformities causing altered structure and function of the first
      metatarsophalangeal joint and subsequent compensatory mechanisms. This study was
      undertaken to determine the relationships between these two deformities and
      transverse plane position of the foot, or angle of gait, and several radiographic
      angular and linear parameters with established reliability. METHODS: A
      convenience sample of 23 subjects with hallux abducto valgus, 22 subjects with
      hallux limitus, and 20 control subjects was used. Radiographic parameters were
      standardized weightbearing views and included lateral stressed dorsiflexion of
      the first metatarsophalangeal joint, composite, dorsoplantar, and lateral views.
      Angle of gait was obtained from powdered footprints recorded on paper. Two left
      and two right footprints identified on each trial were used to calculate angle of
      gait. RESULTS: The findings of the study suggest that an association between
      angle of gait and the presence of hallux abducto valgus or hallux limitus does
      not exist. Possible explanations may relate to the large variability of normal
      angle of gait, the need to identify factors extrinsic to the foot capable of
      affecting transverse plane orientation of the foot, and the addition of
      information relating to symptoms. CONCLUSIONS: In this study, the presence of
      hallux abducto valgus or hallux limitus did not correspond to an association with
      a particular angle of gait. Length and elevation of the first metatarsal were
      associated in subjects with hallux abducto valgus and hallux limitus.

PMID- 17507526
TI  - Complications associated with distraction osteogenesis for the correction of
      brachymetatarsia: a review of five procedures.
AB  - BACKGROUND: Congenital brachymetatarsia is often treated with callus distraction.
      This technique is associated with a variety of complications. We investigated
      complications encountered in treatment of brachymetatarsia in four female
      patients and reviewed adjunctive procedures performed to treat these
      complications. METHODS: We reviewed five distraction osteogenesis procedures
      performed in four female patients with congenital shortening of the fourth
      metatarsal over a 3-year period. Serial radiographs were obtained weekly until
      bone consolidation was achieved, at which time the external fixator was removed.
      Follow-up ranged from 5 to 10 months. RESULTS: Three patients (four metatarsals)
      were satisfied with the cosmetic and functional outcomes of their procedure. One
      patient was dissatisfied with the cosmetic result owing to a short digit from a
      short proximal phalanx but was completely functional and resumed all of her
      normal activities. Complications associated with callus distraction were
      decreased range of motion and stiffness at the metatarsophalangeal joint, flexion
      deformity of the digit, angulation of the metatarsal, prolonged distraction time
      due to pain, fracture of the bone callus, pin-site infection, and an undesirable
      cosmetic appearance due to a short proximal phalanx. Adjunctive procedures were
      needed in some of these cases and yielded good results. CONCLUSIONS: Callus
      distraction is an effective treatment for congenital shortening of the fourth
      metatarsal, but the procedure is associated with a number of complications.
      Because most patients proceed with surgery for cosmetic reasons, it is important
      to present the possible complications and the adjunctive surgical procedures that
      may be necessary for a desirable outcome.

PMID- 17507527
TI  - Ciclopirox 8% nail lacquer topical solution for the treatment of onychomycosis in
      patients with diabetes: a multicenter, open-label study.
AB  - BACKGROUND: An open-label, noncomparative study was conducted to assess the
      safety and efficacy of ciclopirox 8% nail lacquer topical solution in patients
      with type 2 diabetes mellitus. METHODS: Forty-nine diabetic patients with distal
      subungual onychomycosis were treated once daily for 48 weeks with ciclopirox 8%
      nail lacquer, a topical nail solution approved for the treatment of patients with
      mild-to-moderate onychomycosis. RESULTS: Treatment resulted in clinical
      improvement in 63.4% of patients. Most patients (85.7%) had a mycologic outcome
      of improvement or cure, with 54.3% attaining mycologic cure. Consideration of
      mycologic and clinical outcomes generated a treatment outcome of improvement,
      success, or cure in 84.4% of patients. Moreover, patients experienced improvement
      in the diseased area of the nail (63.4%), nail surface (56.1%), nail color
      (48.8%), and nail thickness (65.9%). Ciclopirox 8% nail lacquer was safe, with
      treatment-related adverse events limited to infection in one patient, which
      resolved in 15 days; the patient completed the study. No treatment-related
      serious adverse events were observed. CONCLUSION: Ciclopirox 8% nail lacquer is a
      safe and effective treatment for distal subungual onychomycosis in patients with
      type 2 diabetes mellitus receiving insulin or oral hypoglycemic therapy.

PMID- 17507528
TI  - Efficacy of chemical neurolysis for the treatment of interdigital nerve
      compression of the foot: a retrospective study.
AB  - BACKGROUND: Dilute alcohol injection has been described as a nonsurgical
      treatment option for interdigital nerve compression of the foot, also known as
      "Morton's neuroma." This study reviews the efficacy of the procedure in 49 feet
      at one treatment center. METHODS: In this historical cohort study, data from 42
      patients who had undergone alcohol injection therapy were obtained from clinic
      records. A total of 49 feet were reviewed. RESULTS: Symptoms were improved or
      resolved in 30 (61%) of 49 feet. Nineteen feet (39%) were unimproved, with 12 of
      those progressing to surgical neurectomy. Feet that received five or more
      injections were more likely to improve (74%) than those that received fewer than
      five injections (39%). Three patients reported mild complications associated with
      dilute alcohol injection, all of which resolved spontaneously within 2 days of
      the injection. CONCLUSIONS: Dilute alcohol injection is a safe and effective
      treatment option for patients with Morton's neuroma who want to avoid a surgical
      procedure and any associated complications. The procedure may be more successful
      if the patient receives at least five injections.

PMID- 17507529
TI  - Relationship between positive clinical outcomes of foot orthotic treatment and
      changes in rearfoot kinematics.
AB  - BACKGROUND: Previous two-dimensional kinematic studies that assessed the effect
      of foot orthoses on rearfoot motion have yielded mixed results regarding whether
      control of rearfoot motion is related to symptom relief. METHODS: We sought to
      determine the effect of foot orthoses on rearfoot motion and to correlate these
      changes with the degree of symptom improvement in 22 individuals with excessive
      rearfoot pronation (17 women and 5 men; mean +/- SD age, 44.3 +/- 16.7 years;
      mean +/- SD weight, 74.9 +/- 15.9 kg). Two-dimensional motion-analysis software
      was used to assess frontal plane rearfoot motion with and without foot orthoses.
      The mean +/- SD Foot Posture Index of the left foot was 8.83 +/- 3.54 and of the
      right foot was 9.22 +/- 3.64). The pain and function subscales of the Foot Health
      Status Questionnaire were then used to determine the degree of symptom relief
      associated with the orthoses at baseline and 4 weeks later. RESULTS: Orthoses had
      a small but statistically significant effect on rearfoot motion, although no
      significant correlations were found between differences in rearfoot motion with
      and without foot orthoses and the improvements demonstrated in the Foot Health
      Status Questionnaire subscales of pain and function. CONCLUSIONS: The effect of
      orthoses on frontal plane rearfoot motion is considered small and probably
      insufficient to account for the extent of symptom reduction found in this study.
      Other parameters of orthotic function, such as kinetic and neuromechanical
      variables, should be further investigated.

PMID- 17507530
TI  - Foot pathology and inappropriate footwear as risk factors for falls in a subacute
      aged-care hospital.
AB  - BACKGROUND: Falls are a major clinical problem in the hospital setting. This
      study examined the prevalence of foot pathology and footwear type likely to
      increase the risk of falls in two subacute-care hospital wards serving elderly
      patients. METHODS: Two wards of a subacute aged-care hospital were selected for
      study. Patients were assessed for the presence of foot pathology, and their
      footwear was evaluated for characteristics identified in the literature as
      placing individuals at increased risk of falls. RESULTS: Of 44 patients assessed,
      98% had foot pathology, and 41% had foot pathology requiring podiatric medical
      management. Eighty-six percent of inpatients wore footwear that was likely to
      increase their risk of falls, with 66% wearing slippers or moccasins.
      CONCLUSIONS: The results of this study demonstrate the need for hospital
      inpatients who are identified as being at high risk for falling, or have a
      history of falls, to undergo an assessment of their foot pathology and footwear
      so that appropriate measures can be taken to address these risk factors.

PMID- 17507531
TI  - An uncommon presentation of malignant fibrous histiocytoma of the calcaneus.
AB  - Malignant fibrous histiocytoma of bone is the osseous counterpart of the tumor in
      soft tissue. It is a rare primary bone tumor, and there have been conflicting
      reports on its grades of malignancy. The appendicular skeleton, especially the
      femur, is the most common site of involvement, whereas the calcaneus is rarely
      involved. We describe a primary malignant fibrous histiocytoma of the calcaneal
      bone in a 21-year-old man. The patient underwent neoadjuvant and adjuvant
      chemotherapy and below-the-knee amputation, and no local recurrence or metastasis
      was noted after 2 years of follow-up.

PMID- 17507532
TI  - Chondromyxoid fibroma of the calcaneus.
AB  - Chondromyxoid fibroma is a rare, benign, aggressive bone tumor whose localization
      in the calcaneus is even rarer. We report a case of chondromyxoid fibroma in the
      calcaneus of a 10-year-old Iranian boy who was treated with extended curettage.
      After 3 years of follow-up, the patient had experienced no recurrence.

PMID- 17507533
TI  - Giant cell tumor of the talar neck.
AB  - We describe a patient with a giant cell tumor in the talar head and neck of the
      left foot who was diagnosed as having osteochondritis dissecans and treated with
      arthroscopic drilling in this same location 3 years earlier. Giant cell tumors
      can be confused with several conditions, including giant cell reparative
      granulomas, brown tumors, and aneurysmal bone cysts. Giant cell tumors of bone
      typically occur in the epiphysis of long bones, including the distal femur and
      proximal tibia. They are uncommonly found in the small bones of the foot or
      ankle, and talar involvement is rare. Despite this rarity, the radiographic
      appearance and clinical signs of talar lesions should be considered in the
      differential diagnosis of nontraumatic conditions in the foot.

PMID- 17507534
TI  - Post-traumatic myositis ossificans circumscripta: an unusually large example.
AB  - A 66-year-old woman presented with painful gait and a large, firm, nonmobile mass
      in her right foot. She had undergone four previous surgeries to remove a
      recurring "calcified hematoma" that resulted from an injury sustained 3 decades
      previously. An unusually large ossific mass (7.0 x 7.0 x 2.0 cm) consistent with
      post-traumatic myositis ossificans circumscripta was excised. After 3 years of
      follow-up, there was no return of the symptoms or the mass.

PMID- 17507535
TI  - Exercise-induced rhabdomyolysis.
AB  - Rhabdomyolysis is a debilitating condition that promotes muscle breakdown and
      eventually leads to renal dysfunction if not properly managed. The initial
      presentation may involve lower-extremity muscles, making the foot and ankle
      specialist one of the first specialists to recognize and diagnose this condition.
      Proper management of renal function is the primary concern; however, the
      underlying muscle breakdown needs to be addressed and the condition managed to
      prevent future problems. In this article we discuss treatment of a patient with
      exercise-induced rhabdomyolysis; a rehabilitation regimen is presented whose
      purpose is to condition muscles in order to prevent recurrence of exercise
      induced muscle destruction after an acute event.

PMID- 17507536
TI  - Arthroscopic removal of a subperiosteal osteoid osteoma of the talus.
AB  - We report a case of a subperiosteal osteoid osteoma on the talar neck that was
      removed arthroscopically. Intralesional excision, en bloc resection, and
      percutaneous ablation techniques have all been used for the treatment of osteoid
      osteoma. For intra-articular osteoid osteomas, arthroscopy-assisted removal of
      the tumor has been described in a few case reports. Obtaining a nidus fragment
      for pathologic evaluation is important during arthroscopic removal of intra
      articular osteoid osteomas. Sometimes it is not possible to obtain a specimen for
      pathologic examination. In the present case, the osteoid osteoma on the talar
      neck was easily located, the nidus was completely removed, and the tumor was
      extirpated.

PMID- 17507537
TI  - A simple technique for performing percutaneous fixation of fifth metatarsal base
      fractures.

PMID- 17507538
TI  - Atypical gout in the foot and ankle secondary to primary hyperparathyroidism.

PMID- 17507541
TI  - Recombinant Mycobacterium bovis bacillus Calmette-Guerin elicits human
      immunodeficiency virus type 1 envelope-specific T lymphocytes at mucosal sites.
AB  - A successful vaccine vector for human immunodeficiency virus type 1 (HIV-1)
      should induce anti-HIV-1 T-cell immune responses at mucosal sites. We have
      constructed recombinant Mycobacterium bovis bacillus Calmette-Guerin (rBCG)
      expressing an HIV-1 group M consensus envelope (Env) either as a surface,
      intracellular, or secreted protein as an immunogen. rBCG containing HIV-1 env
      plasmids engineered for secretion induced optimal Env-specific T-cell gamma
      interferon enzyme-linked immunospot responses in murine spleen, female
      reproductive tract, and lungs. While rBCG-induced T-cell responses to HIV-1
      envelope in spleen were lower than those induced by adenovirus prime/recombinant
      vaccinia virus (rAd-rVV) boost, rBCG induced comparable responses to rAd-rVV
      immunization in the female reproductive tract and lungs. T-cell responses induced
      by rBCG were primarily CD4(+), although rBCG alone did not induce anti-HIV-1
      antibody. However, rBCG could prime for a protein boost by HIV-1 envelope
      protein. Thus, rBCG can serve as a vector for induction of anti-HIV-1 consensus
      Env cellular responses at mucosal sites.

PMID- 17507542
TI  - Opsonophagocytic activity and other serological indications of Bordetella
      pertussis infection in military recruits in Norway.
AB  - Bordetella pertussis is the causative agent of pertussis (whooping cough).
      Despite high vaccination coverage, pertussis remains a significant disease in
      many countries. Besides vaccination, transient carriage of Bordetella spp. or
      other cross-reacting organisms adds to the immunity against pertussis. However,
      the various immunological mechanisms conferring protection remain largely
      unknown. In this study, paired serum samples from 464 healthy Norwegian military
      recruits were collected, the first at enrolment and the second about 8 months
      later. The prevalence of pertussis during military service was examined by
      comparing the paired serum samples for immunoglobulin G (IgG) antibodies against
      pertussis toxin (PT) by enzyme-linked immunosorbent assay (ELISA). Seventy-eight
      percent of the recruits had low levels of IgG antibodies against PT in both
      samples. Conversely, 8.4% of the recruits demonstrated high anti-PT IgG levels in
      the first sample, indicative of recent pertussis prior to enrolment. One recruit
      experienced seroconversion, indicating pertussis during service. A subset of 248
      serum samples with low, medium, and high anti-PT IgG titers were analyzed by a
      different ELISA kit for IgG and IgA antibodies against PT and filamentous
      hemagglutinin (FHA) and for opsonophagocytic activity (OPA), for induction of C3b
      deposition products, and for IgG binding with live B. pertussis as the antigen.
      We observed high correlations between OPA and IgG against live bacteria (r =
      0.83), between OPA and IgG anti-FHA (r = 0.79), between OPA and anti-PT IgG (r =
      0.68), and between OPA and C3b binding (r = 0.70) (P < 0.0001 for all). Anti-PT
      IgA did not correlate closely with the other assays.

PMID- 17507543
TI  - Discrepancy between Mycobacterium tuberculosis-specific gamma interferon release
      assays using short and prolonged in vitro incubation.
AB  - The sensitivities of various gamma interferon release assays (IGRAs) for the
      detection of past latent Mycobacterium tuberculosis infection are not known. In
      this study, we aimed to assess the effects of various IGRA formats and in vitro
      incubation periods on test outcome. The results of the tuberculin skin test (TST)
      were compared with those of the QuantiFERON-TB Gold in-tube (QFT-GIT) test, an
      overnight enzyme-linked immunospot assay (ELISPOT), and a 6-day lymphocyte
      stimulation test (LST) by using the same M. tuberculosis-specific peptides and
      samples from 27 TST-positive persons with a history of exposure to M.
      tuberculosis, 4 patients cured of tuberculosis (TB), and 9 TST-negative controls.
      Among the TST-positive persons, the LST was more frequently positive (92%; P <
      0.01) than either the QFT-GIT test (33%) or ELISPOT (46%). While good agreement
      was observed between the QFT-GIT test and ELISPOT (kappa = 0.71) and between TST
      and LST (kappa = 0.78), the agreement between TST or LST, on the one hand, and
      the QFT-GIT test or ELISPOT, on the other, was poor. These data indicate that the
      QFT-GIT test and overnight ELISPOT are less sensitive for the detection of past
      latent TB than the 6-day LST. The observed discrepancies between these IGRAs are
      most likely related to differences in incubation periods. Whether TST-positive
      persons with positive LST results but negative QFT-GIT and ELISPOT results are at
      risk for the development of TB needs to be elucidated before short-incubation
      IGRAs can be used for the screening of individuals for latent TB before
      immunosuppressive treatment.

PMID- 17507544
TI  - Chronic alcoholism alters systemic and pulmonary glutathione redox status.
AB  - RATIONALE: Previous studies have linked the development and severity of acute
      respiratory distress syndrome with a history of alcohol abuse. In clinical
      studies, this association has been centered on depletion of pulmonary glutathione
      and subsequent chronic oxidant stress. OBJECTIVES: The impact on redox potential
      of the plasma or pulmonary pools, however, has never been reported. METHODS:
      Plasma and bronchoalveolar lavage fluid were collected from otherwise healthy
      alcohol-dependent subjects and control subjects matched by age, sex, and smoking
      history. MEASUREMENTS AND MAIN RESULTS: Redox potential was calculated from
      measured reduced and oxidized glutathione in plasma and lavage. Among subjects
      who did and did not smoke, lavage fluid glutathione redox potential was more
      oxidized in alcohol abusers by approximately 40 mV, which was not altered by
      dilution. This oxidation of the airway lining fluid associated with chronic
      alcohol abuse was independent of smoking history. A shift by 20 mV in plasma
      glutathione redox potential, however, was noted only in subjects who both abused
      alcohol and smoked. CONCLUSIONS: Chronic alcoholism was associated with alveolar
      oxidation and, with smoking, systemic oxidation. However, systemic oxidation did
      not accurately reflect the dramatic alcohol-induced oxidant stress in the
      alveolar space. Although there was compensation for the oxidant stress caused by
      smoking in control groups, the capacity to maintain a reduced environment in the
      alveolar space was overwhelmed in those who abused alcohol. The significant
      alcohol-induced chronic oxidant stress in the alveolar space and the subsequent
      ramifications may be an important modulator of the increased incidence and
      severity of acute respiratory distress syndrome in this vulnerable population.

PMID- 17507545
TI  - Global strategy for the diagnosis, management, and prevention of chronic
      obstructive pulmonary disease: GOLD executive summary.
AB  - Chronic obstructive pulmonary disease (COPD) remains a major public health
      problem. It is the fourth leading cause of chronic morbidity and mortality in the
      United States, and is projected to rank fifth in 2020 in burden of disease
      worldwide, according to a study published by the World Bank/World Health
      Organization. Yet, COPD remains relatively unknown or ignored by the public as
      well as public health and government officials. In 1998, in an effort to bring
      more attention to COPD, its management, and its prevention, a committed group of
      scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the
      World Health Organization to form the Global Initiative for Chronic Obstructive
      Lung Disease (GOLD). Among the important objectives of GOLD are to increase
      awareness of COPD and to help the millions of people who suffer from this disease
      and die prematurely of it or its complications. The first step in the GOLD
      program was to prepare a consensus report, Global Strategy for the Diagnosis,
      Management, and Prevention of COPD, published in 2001. The present, newly revised
      document follows the same format as the original consensus report, but has been
      updated to reflect the many publications on COPD that have appeared. GOLD
      national leaders, a network of international experts, have initiated
      investigations of the causes and prevalence of COPD in their countries, and
      developed innovative approaches for the dissemination and implementation of COPD
      management guidelines. We appreciate the enormous amount of work the GOLD
      national leaders have done on behalf of their patients with COPD. Despite the
      achievements in the 5 years since the GOLD report was originally published,
      considerable additional work is ahead of us if we are to control this major
      public health problem. The GOLD initiative will continue to bring COPD to the
      attention of governments, public health officials, health care workers, and the
      general public, but a concerted effort by all involved in health care will be
      necessary.

PMID- 17507546
TI  - Nontuberculous mycobacterial sensitization in the United States: national trends
      over three decades.
AB  - RATIONALE: The prevalence of pulmonary nontuberculous mycobacterial (NTM)
      infections in the United States appears to be rising, but it is unclear if this
      is due to enhanced detection or actual increases in the burden of infection.
      Temporal changes in the epidemiology of Mycobacterium intracellulare
      sensitization may help explain recently observed trends in pulmonary NTM
      infections. OBJECTIVES: Describe the epidemiology of M. intracellulare
      sensitization in the United States in 1971-1972 and 1999-2000. METHODS: We
      studied nationally representative cohorts of the United States'
      noninstitutionalized civilian population participating in the 1971-1972 and 1999
      2000 National Health and Nutrition Examination Surveys (NHANES). Participants
      were skin tested with M. intracellulare antigen and sensitization prevalence was
      compared across NHANES surveys and between participant subgroups. Logistic
      regression was used to identify associations between participant characteristics,
      environmental factors, and NTM sensitization. MEASUREMENTS AND MAIN RESULTS: The
      1971-1972 and 1999-2000 NHANES cohorts included 1,490 and 7,384 individuals,
      respectively. Between 1971-1972 and 1999-2000, the prevalence of M.
      intracellulare sensitization increased from 11.2% (95% confidence interval, 9.2
      13.5%) to 16.6% (95% confidence interval, 13.2-20.6%). On multivariate analysis
      of the 1999-2000 cohort, age, sex, race, birthplace, education, and occupation
      were strongly associated with M. intracellulare sensitization. CONCLUSIONS: In
      1999-2000, an estimated one in six persons in the United States demonstrated M.
      intracellulare sensitization, up from one in nine persons in 1971-1972. The
      observed rising prevalence of sensitization is consistent with observed increases
      in the rates of pulmonary NTM infections in the United States.

PMID- 17507547
TI  - Indoor air quality in homes of patients with chronic obstructive pulmonary
      disease.
AB  - RATIONALE: Outdoor air quality is associated with respiratory morbidity and
      mortality. Less is known of the relationship of indoor air quality to respiratory
      health of groups vulnerable to outdoor air, such as those with chronic
      obstructive pulmonary disease (COPD). OBJECTIVES: To investigate among patients
      with COPD the association of health status with indoor air quality in their
      homes. METHODS: Observational study of indoor environmental characteristics of
      homes of 148 patients with severe COPD in North East Scotland. MEASUREMENTS AND
      MAIN RESULTS: Airborne living room levels of particulate matter with a diameter
      of 2.5 microm or less (PM(2.5)) (microg/m(3)) were measured over 8 to 14 hours
      using DustTrak monitors. Nitrogen dioxide exposure (ppb) in living rooms was
      measured over 1 week. Endotoxin (EU [endotoxin units]/mg) in living room dust was
      measured. Health status of participants was assessed by the St. George's
      Respiratory Health Questionnaire (symptoms, activity limitation, and disease
      impact). The mean age of participants was 69 years. Approximately 45% were male,
      39% were smokers, and 49% lived in smoking households. Average indoor PM(2.5)
      levels were 18 mug/m(3), nitrogen dioxide was 7.8 ppb, and endotoxin levels were
      95.8 EU/mg of dust. PM(2.5) was significantly higher in smoking households (P <
      0.001) and was associated with higher levels of endotoxin and NO(2). PM(2.5) was
      significantly associated with increased symptom burden (P < 0.01), with greater
      effect for current smokers. Endotoxin and nitrogen dioxide exposure were not
      related to health status. CONCLUSIONS: Higher levels of PM(2.5) are associated
      with worse health status of these patients with severe COPD. Indoor levels of
      PM(2.5) are significantly higher in homes with smokers.

PMID- 17507548
TI  - Butanone: the memory of a scent.

PMID- 17507549
TI  - Seeing things: illusory contours in the human visual brain.

PMID- 17507550
TI  - Genetic single-cell mosaic analysis implicates ephrinB2 reverse signaling in
      projections from the posterior tectum to the hindbrain in zebrafish.
AB  - The optic tectum is a visual center in vertebrates. It receives topographically
      ordered visual inputs from the retina in the superficial layers and then sends
      motor outputs from the deeper layers to the premotor reticulospinal system in the
      hindbrain. Although the topographic patterns of the retinotectal projection are
      well known, it is not yet well understood how tectal efferents in the tectobulbar
      tract project to the hindbrain. The retinotectal and the tectobulbar projections
      were visualized in a zebrafish stable transgenic line Tg(brn3a-hsp70:GFP). Using
      a single-neuron labeling system in combination with the cre/loxP and Gal4/UAS
      systems, we showed that the tectal neurons that projected to rhombomeres 2 and 6
      were distributed with distinctive patterns along the anterior-posterior axis.
      Furthermore, we found that ephrinB2a was critically involved in increasing the
      probability of neurons projecting to rhombomere 2 through a reverse signaling
      mechanism. These results may provide a neuroanatomical and molecular basis for
      the motor command map in the tectum.

PMID- 17507551
TI  - Inhibition determines membrane potential dynamics and controls action potential
      generation in awake and sleeping cat cortex.
AB  - Intracellular recordings of cortical neurons in awake cat and monkey show a
      depolarized state, sustained firing, and intense subthreshold synaptic activity.
      It is not known what conductance dynamics underlie such activity and how neurons
      process information in such highly stochastic states. Here, we combine
      intracellular recordings in awake and naturally sleeping cats with computational
      models to investigate subthreshold dynamics of conductances and how conductance
      dynamics determine spiking activity. We show that during both wakefulness and the
      "up-states" of natural slow-wave sleep, membrane-potential activity stems from a
      diversity of combinations of excitatory and inhibitory synaptic conductances,
      with dominant inhibition in most of the cases. Inhibition also provides the
      largest contribution to membrane potential fluctuations. Computational models
      predict that in such inhibition-dominant states, spikes are preferentially evoked
      by a drop of inhibitory conductance, and that its signature is a transient drop
      of membrane conductance before the spike. This pattern of conductance change is
      indeed observed in estimates of spike-triggered averages of synaptic conductances
      during wakefulness and slow-wave sleep up states. These results show that
      activated states are defined by diverse combinations of excitatory and inhibitory
      conductances with pronounced inhibition, and that the dynamics of inhibition is
      particularly effective on spiking, suggesting an important role for inhibitory
      processes in both conscious and unconscious cortical states.

PMID- 17507552
TI  - Effects of treadmill exercise on dopaminergic transmission in the 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury.
AB  - Studies have suggested that there are beneficial effects of exercise in patients
      with Parkinson's disease, but the underlying molecular mechanisms responsible for
      these effects are poorly understood. Studies in rodent models provide a means to
      examine the effects of exercise on dopaminergic neurotransmission. Using
      intensive treadmill exercise, we determined changes in striatal dopamine in the 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse. C57BL/6J mice
      were divided into four groups: (1) saline, (2) saline plus exercise, (3) MPTP,
      and (4) MPTP plus exercise. Exercise was started 5 d after MPTP lesioning and
      continued for 28 d. Treadmill running improved motor velocity in both exercise
      groups. All exercised animals also showed increased latency to fall (improved
      balance) using the accelerating rotarod compared with nonexercised mice. Using
      HPLC, we found no difference in striatal dopamine tissue levels between MPTP plus
      exercise compared with MPTP mice. There was an increase detected in saline plus
      exercise mice. Analyses using fast-scan cyclic voltammetry showed increased
      stimulus-evoked release and a decrease in decay of dopamine in the dorsal
      striatum of MPTP plus exercise mice only. Immunohistochemical staining analysis
      of striatal tyrosine hydroxylase and dopamine transporter proteins showed
      decreased expression in MPTP plus exercise mice compared with MPTP mice. There
      were no differences in mRNA transcript expression in midbrain dopaminergic
      neurons between these two groups. However, there was diminished transcript
      expression in saline plus exercise compared with saline mice. Our findings
      suggest that the benefits of treadmill exercise on motor performance may be
      accompanied by changes in dopaminergic neurotransmission that are different in
      the injured (MPTP-lesioned) compared with the noninjured (saline) nigrostriatal
      system.

PMID- 17507553
TI  - Heterosynaptic scaling of developing GABAergic synapses: dependence on
      glutamatergic input and developmental stage.
AB  - A proportionality or balance between coactivated excitatory and inhibitory inputs
      is often observed for individual cortical neurons and is proposed to be important
      for their functions. This feature of neural circuits may arise from coordinated
      modulation of excitatory and inhibitory synaptic inputs, a mechanism that remains
      unknown. Here, in vivo whole-cell recordings from tectal neurons of young Xenopus
      tadpoles reveals activity-dependent bidirectional modifications of GABAergic
      inputs. At early developmental stages when GABAergic inputs dominate visually
      evoked responses, repetitive visual stimulation leads to long-term depression of
      GABAergic inputs. At later stages when convergent glutamatergic inputs are much
      stronger, long-term potentiation (LTP) of GABAergic inputs is induced. The
      polarity of GABAergic plasticity depends on the ratio between the magnitude of
      coactivated glutamatergic and GABAergic inputs (E/I ratio) to the tectal cell:
      LTP is induced only when the E/I ratio is above a threshold, and the level of LTP
      correlates linearly with the logarithm of the E/I ratio. The induction of LTP
      requires the activation of postsynaptic NMDA receptors, as well as presynaptic
      TrkB signaling likely through retrograde BDNF (brain-derived neurotrophic factor)
      and is achieved by overcoming a predominant depression process mediated by NMDA
      receptors on the presynaptic GABAergic neurons. Our results indicate that the
      strength of developing GABAergic synapses can be scaled in accordance to
      coactivated convergent glutamatergic input. This mechanism may contribute to the
      formation of functional neural circuits with correlated excitatory and inhibitory
      inputs.

PMID- 17507554
TI  - Wnt-7a induces presynaptic colocalization of alpha 7-nicotinic acetylcholine
      receptors and adenomatous polyposis coli in hippocampal neurons.
AB  - Nicotinic acetylcholine receptors (nAChRs) contribute significantly to
      hippocampal function. Alpha7-nAChRs are present in presynaptic sites in
      hippocampal neurons and may influence transmitter release, but the factors that
      determine their presynaptic localization are unknown. We report here that Wnt-7a,
      a ligand active in the canonical Wnt signaling pathway, induces dissociation of
      the adenomatous polyposis coli (APC) protein from the beta-catenin cytoplasmic
      complex and the interaction of APC with alpha7-nAChRs in hippocampal neurons.
      Interestingly, Wnt-7a induces the relocalization of APC to membranes, clustering
      of APC in neurites, and coclustering of APC with different, presynaptic protein
      markers. Wnt-7a also increases the number and size of coclusters of alpha7-nAChRs
      and APC in presynaptic terminals. These short-term changes in alpha7-nAChRs occur
      in the few minutes after ligand exposure and involve translocation to the plasma
      membrane without affecting total receptor levels. Longer-term exposure to Wnt-7a
      increases nAChR alpha7 subunit levels in an APC-independent manner and increases
      clusters of alpha7-nAChRs in neurites via an APC-dependent process. Together,
      these results demonstrate that stimulation through the canonical Wnt pathway
      regulates the presynaptic localization of APC and alpha7-nAChRs with APC serving
      as an intermediary in the alpha7-nAChR relocalization process. Modulation by Wnt
      signaling may be essential for alpha7-nAChR expression and function in synapses.

PMID- 17507555
TI  - Visual topography of human intraparietal sulcus.
AB  - Human parietal cortex is implicated in a wide variety of sensory and cognitive
      functions, yet its precise organization remains unclear. Visual field maps
      provide a potential structural basis for descriptions of functional organization.
      Here, we detail the topography of a series of five maps of the contralateral
      visual hemifield within human posterior parietal cortex. These maps are located
      along the medial bank of the intraparietal sulcus (IPS) and are revealed by
      direct visual stimulation during functional magnetic resonance imaging, allowing
      these parietal regions to be routinely and reliably identified simultaneously
      with occipital visual areas. Two of these maps (IPS3 and IPS4) are novel, whereas
      two others (IPS1 and IPS2) have previously been revealed only by higher-order
      cognitive tasks. Area V7, a previously identified visual map, is observed to lie
      within posterior IPS and to share a foveal representation with IPS1. These
      parietal maps are reliably observed across scan sessions; however, their precise
      topography varies between individuals. The multimodal organization of posterior
      IPS mirrors this variability in visual topography, with complementary tactile
      activations found immediately adjacent to the visual maps both medially and
      laterally. These visual maps may provide a practical framework in which to
      characterize the functional organization of human IPS.

PMID- 17507556
TI  - Dysregulated metabotropic glutamate receptor-dependent translation of AMPA
      receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of
      fragile X syndrome.
AB  - Fragile X syndrome, a common form of inherited mental retardation, is caused by
      the loss of fragile X mental retardation protein (FMRP), an mRNA binding protein
      that is hypothesized to regulate local mRNA translation in dendrites downstream
      of gp1 metabotropic glutamate receptors (mGluRs). However, specific FMRP
      associated mRNAs that localize to dendrites in vivo and show altered mGluR
      dependent translation at synapses of Fmr1 knock-out mice are unknown so far.
      Using fluorescence in situ hybridization, we discovered that GluR1/2 and
      postsynaptic density-95 (PSD-95) mRNAs are localized to dendrites of cortical and
      hippocampal neurons in vivo. Quantitative analyses of their dendritic mRNA levels
      in cultured neurons and synaptoneurosomes did not detect differences between wild
      type and Fmr1 knock-out (KO) mice. In contrast, PSD-95, GluR1/2, and
      calcium/calmodulin-dependent kinase IIalpha (CaMKIIalpha) mRNA levels in actively
      translating polyribosomes were dysregulated in synaptoneurosomes from Fmr1 knock
      out mice in response to mGluR activation. [35S]methionine incorporation into
      newly synthesized proteins similarly revealed impaired stimulus-induced protein
      synthesis of CaMKIIalpha and PSD-95 in synaptoneurosomes from Fmr1 KO mice.
      Quantitative analysis of mRNA levels in FMRP-specific immunoprecipitations from
      synaptoneurosomes demonstrated the association of FMRP with CaMKIIalpha, PSD-95,
      and GluR1/2 mRNAs. These findings suggest a novel mechanism whereby FMRP
      regulates the local synthesis AMPA receptor (AMPAR) subunits, PSD-95, and
      CaMKIIalpha downstream of mGluR-activation. Dysregulation of local translation of
      AMPAR and associated factors at synapses may impair control of the molecular
      composition of the postsynaptic density and consequently alter synaptic
      transmission, causing impairments of neuronal plasticity observed in Fmr1 knock
      out mice and fragile X syndrome.

PMID- 17507558
TI  - Changes in synaptic morphology accompany actin signaling during LTP.
AB  - Stabilization of long-term potentiation (LTP) is commonly proposed to involve
      changes in synaptic morphology and reorganization of the spine cytoskeleton. Here
      we tested whether, as predicted from this hypothesis, induction of LTP by theta
      burst stimulation activates an actin regulatory pathway and alters synapse
      morphology within the same dendritic spines. TBS increased severalfold the
      numbers of spines containing phosphorylated (p) p21-activated kinase (PAK) or its
      downstream target cofilin; the latter regulates actin filament assembly. The
      PAK/cofilin phosphoproteins were increased at 2 min but not 30 s post-TBS, peaked
      at 7 min, and then declined. Double immunostaining for the postsynaptic density
      protein PSD95 revealed that spines with high pPAK or pCofilin levels had larger
      synapses (+60-70%) with a more normal size frequency distribution than did
      neighboring spines. Based on these results and simulations of shape changes to
      synapse-like objects, we propose that theta stimulation markedly increases the
      probability that a spine will enter a state characterized by a large, ovoid
      synapse and that this morphology is important for expression and later
      stabilization of LTP.

PMID- 17507557
TI  - Protein kinase C delta negatively regulates tyrosine hydroxylase activity and
      dopamine synthesis by enhancing protein phosphatase-2A activity in dopaminergic
      neurons.
AB  - Tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, can be
      regulated by phosphorylation at multiple serine residues, including serine-40. In
      the present study, we report a novel interaction between a key member of the
      novel PKC family, protein kinase Cdelta (PKCdelta), and TH, in which the kinase
      modulates dopamine synthesis by negatively regulating TH activity via protein
      phosphatase 2A (PP2A). We observed that PKCdelta is highly expressed in nigral
      dopaminergic neurons and colocalizes with TH. Interestingly, suppression of
      PKCdelta activity with the kinase inhibitor rottlerin, PKCdelta-small interfering
      RNA, or with PKCdelta dominant-negative mutant effectively increased a number of
      key biochemical events in the dopamine pathway, including TH-ser40
      phosphorylation, TH enzymatic activity, and dopamine synthesis in neuronal cell
      culture models. Additionally, we found that PKCdelta not only physically
      associates with the PP2A catalytic subunit (PP2Ac) but also phosphorylates the
      phosphatase to increase its activity. Notably, inhibition of PKCdelta reduced the
      dephosphorylation activity of PP2A and thereby increased TH-ser40
      phosphorylation, TH activity, and dopamine synthesis. To further validate our
      findings, we used the PKCdelta knock-out (PKCdelta-/-) mouse model. Consistent
      with other results, we found greater TH-ser40 phosphorylation and reduced PP2A
      activity in the substantia nigra of PKCdelta-/- mice than in wild-type mice.
      Importantly, this was accompanied by an increased dopamine level in the striatum
      of PKCdelta-/- mice. Collectively, these results suggest that PKCdelta
      phosphorylates PP2Ac to enhance its activity and thereby reduces TH-ser40
      phosphorylation and TH activity and ultimately dopamine synthesis.

PMID- 17507559
TI  - Reinnervation of late postnatal Purkinje cells by climbing fibers:
      neosynaptogenesis without transient multi-innervation.
AB  - Synaptic partner selection and refinement of projections are important in the
      development of precise and functional neuronal connections. We investigated the
      formation of new synaptic connections in a relatively mature system to test
      whether developmental events can be recapitulated at later stages (i.e., after
      the mature synaptic organization has been established), using a model of
      postlesional reinnervation in the olivo-cerebellar pathway. During the
      development of this pathway, synaptic connections between climbing fibers (CFs)
      and Purkinje cells (PCs) are diffuse and redundant before synapse elimination
      refines the pattern. The regression of CFs during the first 2 postnatal weeks in
      the rat leads to mono-innervation of each PC. After unilateral transection of the
      rat olivo-cerebellar pathway and intracerebellar injection of BDNF 24 h after
      lesion, axons from the remaining inferior olive can sprout into the deafferented
      hemicerebellum and establish new contacts with denervated PCs at later
      developmental stages. We found that these contacts are first established on
      somatic thorns before the CFs translocate to the PC dendrites, recapitulating the
      morphological steps of normal CF-PC synaptogenesis, but on a relatively mature
      PC. However, electrophysiology of PC reinnervation by transcommissural CFs in
      these animals showed that each PC is reinnervated by only one CF. This mono
      innervation contrasts with the reinnervation of grafted immature PCs in the same
      cerebellum. Our results provide evidence that relatively mature PCs do not
      receive several olivary afferents during late reinnervation, suggesting a
      critical role of the target cell state in the control of CF-PC synaptogenesis.
      Thus, synapse exuberance and subsequent elimination are not a prerequisite to
      reach a mature relationship between synaptic partners.

PMID- 17507560
TI  - Drosophila Hyperkinetic mutants have reduced sleep and impaired memory.
AB  - In mammals, sleep is thought to be important for health, cognition, and memory.
      Fruit flies share most features of mammalian sleep, and a recent study found that
      Drosophila lines carrying loss-of-function mutations in Shaker (Sh) are short
      sleeping, suggesting that the Sh current plays a major role in regulating daily
      sleep amount. The Sh current is potentiated by a beta modulatory subunit coded by
      Hyperkinetic (Hk). Here, we demonstrate that severe loss-of-function mutations of
      Hk reduce sleep and do so primarily by affecting the Sh current. Moreover, we
      prove, using a transgenic approach, that a wild-type copy of Hk is sufficient to
      restore normal sleep. Furthermore, we show that short-sleeping Hk mutant lines
      have a memory deficit, whereas flies carrying a weaker hypomorphic Hk allele have
      normal sleep and normal memory. By comparing six short-sleeping Sh lines with two
      normal sleeping ones, we also found that only alleles that reduce sleep also
      impair memory. These data identify a gene, Hk, which is necessary to maintain
      normal sleep, and provide genetic evidence that short sleep and poor memory are
      linked.

PMID- 17507561
TI  - Connecting TNF-alpha signaling pathways to iNOS expression in a mouse model of
      Alzheimer's disease: relevance for the behavioral and synaptic deficits induced
      by amyloid beta protein.
AB  - Increased brain deposition of amyloid beta protein (Abeta) and cognitive deficits
      are classical signals of Alzheimer's disease (AD) that have been highly
      associated with inflammatory alterations. The present work was designed to
      determine the correlation between tumor necrosis factor-alpha (TNF-alpha)-related
      signaling pathways and inducible nitric oxide synthase (iNOS) expression in a
      mouse model of AD, by means of both in vivo and in vitro approaches. The
      intracerebroventricular injection of Abeta(1-40) in mice resulted in marked
      deficits of learning and memory, according to assessment in the water maze
      paradigm. This cognition impairment seems to be related to synapse dysfunction
      and glial cell activation. The pharmacological blockage of either TNF-alpha or
      iNOS reduced the cognitive deficit evoked by Abeta(1-40) in mice. Similar results
      were obtained in TNF-alpha receptor 1 and iNOS knock-out mice. Abeta(1-40)
      administration induced an increase in TNF-alpha expression and oxidative
      alterations in prefrontal cortex and hippocampus. Likewise, Abeta(1-40) led to
      activation of both JNK (c-Jun-NH2-terminal kinase)/c-Jun and nuclear factor
      kappaB, resulting in iNOS upregulation in both brain structures. The anti-TNF
      alpha antibody reduced all of the molecular and biochemical alterations promoted
      by Abeta(1-40). These results provide new insights in mouse models of AD,
      revealing TNF-alpha and iNOS as central mediators of Abeta action. These pathways
      might be targeted for AD drug development.

PMID- 17507562
TI  - Sensory deprivation alters aggrecan and perineuronal net expression in the mouse
      barrel cortex.
AB  - An important role for the neural extracellular matrix in modulating cortical
      activity-dependent synaptic plasticity has been established by a number of recent
      studies. However, identification of the critical molecular components of the
      neural matrix that mediate these processes is far from complete. Of particular
      interest is the perineuronal net (PN), an extracellular matrix component found
      surrounding the cell body and proximal neurites of a subset of neurons. Because
      of the apposition of the PN to synapses and expression of this structure
      coincident with the close of the critical period, it has been hypothesized that
      nets could play uniquely important roles in synapse stabilization and maturation.
      Interestingly, previous work has also shown that expression of PNs is dependent
      on appropriate sensory stimulation in the visual system. Here, we investigated
      whether PNs in the mouse barrel cortex are expressed in an activity-dependent
      manner by manipulating sensory input through whisker trimming. Importantly, this
      manipulation did not lead to a global loss of PNs but instead led to a specific
      decrease in PNs, detected with the antibody Cat-315, in layer IV of the barrel
      cortex. In addition, we identified a key activity-regulated component of PNs is
      the proteoglycan aggrecan. We also demonstrate that these Cat-315-positive
      neurons virtually all also express parvalbumin. Together, these data are in
      support of an important role for aggrecan in the activity-dependent formation of
      PNs on parvalbumin-expressing cells and suggest a role for expression of these
      nets in regulating the close of the critical period.

PMID- 17507563
TI  - Functional coupling between the prefrontal cortex and dopamine neurons in the
      ventral tegmental area.
AB  - Stimulation of the prefrontal cortex (PFC) has been shown to have an excitatory
      influence on dopamine (DA) neurons. We report here that, under nonstimulated
      conditions, the activity of DA neurons in the ventral tegmental area (VTA) also
      covaries, on a subsecond timescale, with the activity of PFC cells. Thus, in 67%
      of VTA DA neurons recorded in chloral hydrate-anesthetized rats, the firing of
      the cell displayed a slow oscillation (SO) that was highly coherent with the
      activity of PFC neurons. The SO was suppressed by transections immediately caudal
      to the PFC or by intra-PFC infusion of tetrodotoxin, suggesting that it depends
      on inputs derived from the PFC. Unexpectedly, the SO in most VTA DA neurons was
      reversed in phase relative to PFC cell activity, suggesting that at least part of
      PFC information is transferred to DA neurons indirectly through inhibitory relay
      neurons. These results, together with those reported previously, suggest that the
      PFC can act through multiple pathways to exert both excitatory and inhibitory
      influences on DA neurons. The observed functional coupling between DA and PFC
      neurons further suggests that these pathways not only allow a bidirectional
      control of DA neurons by the PFC, but also enable action potential-dependent DA
      release to be coordinated, on a subsecond timescale, with glutamate release from
      PFC terminals. Further understanding of this coordinated activity may provide
      important new insights into brain functions and disorders thought to involve both
      VTA DA and PFC neurons.

PMID- 17507564
TI  - Monitoring synaptic function at the neuromuscular junction of a mouse expressing
      synaptopHluorin.
AB  - We monitored presynaptic exocytosis and vesicle recycling at neuromuscular
      junctions of transgenic mice expressing synaptopHluorin (spH), using simultaneous
      optical and electrophysiological recordings. Synaptic transmission was
      indistinguishable from that in wild-type controls. Fluorescence rose during and
      decayed monotonically after stimulus trains to the nerve, with amplitudes and
      decay times increasing with the amount of stimulation. The relatively large size
      of synaptic terminals allowed us to examine the spatial profile of fluorescence
      changes. We identified hot spots of exocytosis, which were stable with repeated
      trains. Photobleach experiments showed that spH freshly exposed by nerve
      stimulation was not preferentially retrieved by compensatory endocytosis;
      instead, most retrieved spH preexisted in the surface membrane. Finally, we
      compared fluorescence and electrical [summed end-plate potentials (EPPs)]
      estimates of exocytosis, which diverged during repeated trains, as fluorescence
      exceeded summed EPPs, although the average amplitude of miniature EPPs was
      unchanged. This might reflect exocytosis of spH-containing, acetylcholine-free
      ("empty") vesicles or other organelles during intense stimulation.

PMID- 17507565
TI  - A fast, reciprocal pathway between the lateral geniculate nucleus and visual
      cortex in the macaque monkey.
AB  - Neurons in the lateral geniculate nucleus (LGN) not only provide feedforward
      input to primary visual cortex (V1), but also receive robust feedback from the
      cortex. Accordingly, visual processing in the LGN is continuously influenced by
      previous patterns of activity. This study examines the temporal properties of
      feedforward and feedback pathways between the LGN and V1 in the macaque monkey to
      provide a lower bound on how quickly the cortex can influence the LGN. In so
      doing, we identified a subclass of corticogeniculate neurons that receives
      direct, suprathreshold input from the LGN that is similar in latency to that
      directed to other recipient neurons (4.2 +/- 0.4 vs 4.0 +/- 0.2 ms). These
      neurons also provide feedback to the LGN that is significantly shorter in latency
      than that supplied by corticogeniculate neurons lacking LGN input (5.1 +/- 1.3 vs
      11.1 +/- 2.3 ms, respectively). Across our sample of corticogeniculate neurons,
      the shortest combined visual response latency and feedback latency was 37 ms
      (mean, 52.5 +/- 3.8 ms), indicating that visual signals can rapidly travel from
      the periphery to the cortex and back to the LGN.

PMID- 17507566
TI  - Adhesion is prerequisite, but alone insufficient, to elicit stem cell
      pluripotency.
AB  - Primitive mammalian neural stem cells (NSCs), arising during the earliest stages
      of embryogenesis, possess pluripotency in embryo chimera assays in contrast to
      definitive NSCs found in the adult. We hypothesized that adhesive differences
      determine the association of stem cells with embryonic cells in chimera assays
      and hence their ability to contribute to later tissues. We show that primitive
      NSCs and definitive NSCs possess adhesive differences, resulting from
      differential cadherin expression, that lead to a double dissociation in outcomes
      after introduction into the early- versus midgestation embryo. Primitive NSCs are
      able to sort with the cells of the inner cell mass and thus contribute to early
      embryogenesis, in contrast to definitive NSCs, which cannot. Conversely,
      primitive NSCs sort away from cells of the embryonic day 9.5 telencephalon and
      are unable to contribute to neural tissues at midembryogenesis, in contrast to
      definitive NSCs, which can. Overcoming these adhesive differences by E-cadherin
      overexpression allows some definitive NSCs to integrate into the inner cell mass
      but is insufficient to allow them to contribute to later development. These
      adhesive differences suggest an evolving compartmentalization in multipotent NSCs
      during development and serve to illustrate the importance of cell-cell
      association for revealing cellular contribution.

PMID- 17507567
TI  - Fast vesicle replenishment and rapid recovery from desensitization at a single
      synaptic release site.
AB  - When the synaptic connection between two neurons consists of a small number of
      release sites, the ability to maintain transmission at high frequencies is
      limited by vesicle mobilization and by the response of postsynaptic receptors.
      These two properties were examined at single release sites between granule cells
      and stellate cells by triggering bursts of quantal events either with alpha
      latrotoxin or with high-frequency trains of presynaptic activity. Bursts and
      evoked responses consisted of tens to hundreds of events with frequencies of up
      to hundreds per second. This indicates that single release sites can rapidly
      supply vesicles from a reserve pool to a release-ready pool. In addition,
      postsynaptic AMPA receptors recover from desensitization with a time constant of
      approximately 5 ms. Thus, even for synapses composed of a single release site,
      granule cells can effectively activate stellate cells during sustained high
      frequency transmission because of rapid vesicle mobilization and fast recovery of
      AMPA receptors from desensitization.

PMID- 17507568
TI  - Zic1 and Zic3 regulate medial forebrain development through expansion of neuronal
      progenitors.
AB  - The medial telencephalon is a source of neurons that follow distinct tangential
      trajectories of migration to various structures such as the cerebral cortex,
      striatum, and olfactory bulb. In the present study, we characterized the
      forebrain anomalies in Zic1/Zic3 compound mutant mice. Zic1 and Zic3 were
      strongly expressed in the medial structures, including the septum, medial
      cerebral cortex, and choroid plexus. Mice homozygous for the Zic1 mutant allele
      together with the null Zic3 allele showed medial forebrain defects, which were
      not obvious in either Zic1 or Zic3 single mutants. Absence of both Zic1 and Zic3
      caused hypoplasia of the hippocampus, septum, and olfactory bulb. Analysis of the
      cell cycle revealed that the cell cycle exit rate was increased in the septa of
      double mutants. Misexpression of Zic3 in the ventricular layer of the cerebral
      cortex inhibited neuronal differentiation. These results indicated that both Zic1
      and Zic3 function in maintaining neural precursor cells in an undifferentiated
      state. The functions of these genes may be essential to increasing neural cell
      numbers regionally in the medial telencephalon and to proper mediolateral
      patterning of the telencephalon.

PMID- 17507569
TI  - Learning-induced plasticity in auditory spatial representations revealed by
      electrical neuroimaging.
AB  - Auditory spatial representations are likely encoded at a population level within
      human auditory cortices. We investigated learning-induced plasticity of spatial
      discrimination in healthy subjects using auditory-evoked potentials (AEPs) and
      electrical neuroimaging analyses. Stimuli were 100 ms white-noise bursts
      lateralized with varying interaural time differences. In three experiments,
      plasticity was induced with 40 min of discrimination training. During training,
      accuracy significantly improved from near-chance levels to approximately 75%.
      Before and after training, AEPs were recorded to stimuli presented passively with
      a more medial sound lateralization outnumbering a more lateral one (7:1). In
      experiment 1, the same lateralizations were used for training and AEP sessions.
      Significant AEP modulations to the different lateralizations were evident only
      after training, indicative of a learning-induced mismatch negativity (MMN). More
      precisely, this MMN at 195-250 ms after stimulus onset followed from differences
      in the AEP topography to each stimulus position, indicative of changes in the
      underlying brain network. In experiment 2, mirror-symmetric locations were used
      for training and AEP sessions; no training-related AEP modulations or MMN were
      observed. In experiment 3, the discrimination of trained plus equidistant
      untrained separations was tested psychophysically before and 0, 6, 24, and 48 h
      after training. Learning-induced plasticity lasted <6 h, did not generalize to
      untrained lateralizations, and was not the simple result of strengthening the
      representation of the trained lateralizations. Thus, learning-induced plasticity
      of auditory spatial discrimination relies on spatial comparisons, rather than a
      spatial anchor or a general comparator. Furthermore, cortical auditory
      representations of space are dynamic and subject to rapid reorganization.

PMID- 17507570
TI  - Subunit dissociation and diffusion determine the subcellular localization of rod
      and cone transducins.
AB  - Activation of rod photoreceptors by light induces a massive redistribution of the
      heterotrimeric G-protein transducin. In darkness, transducin is sequestered
      within the membrane-enriched outer segments of the rod cell. In light, it
      disperses throughout the entire neuron. We show here that redistribution of rod
      transducin by light requires activation, but it does not require ATP. This
      observation rules out participation of molecular motors in the redistribution
      process. In contrast to the light-stimulated redistribution of rod transducin in
      rods, cone transducin in cones does not redistribute during activation.
      Remarkably, when cone transducin is expressed in rods, it does undergo light
      stimulated redistribution. We show here that the difference in subcellular
      localization of activated rod and cone G-proteins correlates with their affinity
      for membranes. Activated rod transducin releases from membranes, whereas
      activated cone transducin remains bound to membranes. A synthetic peptide that
      dissociates G-protein complexes independently of activation facilitates
      dispersion of both rod and cone transducins within the cells. This peptide also
      facilitates detachment of both G-proteins from the membranes. Together, these
      results show that it is the dissociation state of transducin that determines its
      localization in photoreceptors. When rod transducin is stimulated, its subunits
      dissociate, leave outer segment membranes, and equilibrate throughout the cell.
      Cone transducin subunits do not dissociate during activation and remain
      sequestered within the outer segment. These findings indicate that the subunits
      of some heterotrimeric G-proteins remain associated during activation in their
      native environments.

PMID- 17507571
TI  - Prolonged glial expression of Sox4 in the CNS leads to architectural cerebellar
      defects and ataxia.
AB  - Sox proteins of group C are strongly expressed in the developing nervous system
      and have been associated with maturation of neurons and glia. Here, we
      overexpressed the group C protein Sox4 in transgenic mice under the control of
      the human GFAP promoter. Transgene expression was detected in radial glia and
      astrocytes throughout the CNS. The transgenic mice were ataxic and exhibited
      hydrocephaly as well as cerebellar malformations. In the cerebellum, fissures
      were not formed and neuronal layering was dramatically disturbed. Nevertheless,
      all neuronal cell types of the cerebellum were present as well as cells with
      characteristics of early radial glia, astrocytes, and oligodendrocytes. However,
      radial glia failed to migrate into the position normally taken by Bergmann glia
      and did not extend radial fibers toward the pial surface. The cerebellar
      malformations can therefore be explained by the absence of functional Bergmann
      glia. We conclude that Sox4 expression counteracts differentiation of radial glia
      and has to be downregulated before full maturation can occur.

PMID- 17507572
TI  - Impulsive personality predicts dopamine-dependent changes in frontostriatal
      activity during component processes of working memory.
AB  - Dopaminergic drugs affect a variety of cognitive processes, but the direction and
      extent of effects vary across individuals and tasks. Paradoxical effects are
      observed, by which the same drug causes cognitive enhancing as well as adverse
      effects. Here, we demonstrate that individual differences in impulsive
      personality account for the contrasting effects of dopaminergic drugs on working
      memory and associated frontostriatal activity. We observed that the dopamine D2
      receptor agonist bromocriptine improved the flexible updating (switching) of
      relevant information in working memory in high-impulsive subjects, but not in low
      impulsive subjects. These behavioral effects in high-impulsive subjects
      accompanied dissociable effects on frontostriatal activity. Bromocriptine
      modulated the striatum during switching but not during distraction from relevant
      information in working memory. Conversely, the lateral frontal cortex was
      modulated by bromocriptine during distraction but not during switching. The
      present results provide a key link between dopamine D2 receptor function,
      impulsivity, and frontostriatal activity during component processes of working
      memory.

PMID- 17507573
TI  - The dorsolateral prefrontal cortex contributes to successful relational memory
      encoding.
AB  - Results from neuroimaging studies of long-term memory (LTM) encoding have
      contributed to the view that the ventrolateral prefrontal cortex (VLPFC)
      contributes to successful LTM formation, whereas the dorsolateral prefrontal
      cortex (DLPFC) does not. We hypothesized that the DLPFC does contribute to LTM,
      but under specific circumstances. That is, the DLPFC may be critical for building
      relationships between items during on-line processing, and this may promote LTM
      for associations between items. We used event-related functional magnetic
      resonance imaging (fMRI) to test this hypothesis by examining brain activity
      during sequential encoding of unrelated word pairs. During presentation of the
      second ("target") word in each pair, subjects either made a semantic judgment
      specific to the target word ("item-specific" trials), or a semantic judgment that
      involved a comparison between the target word and the first word in the pair
      ("relational" trials). Behaviorally, recognition memory for target words was
      equivalent between the two trial types but associative recognition of studied
      word pairs was significantly greater for relational trials. fMRI results showed
      that DLPFC activity was greater during relational compared with item-specific
      encoding and that DLPFC activity predicted successful memory for associations but
      not successful item memory. Activity in the VLPFC was also greater for relational
      compared with item-specific encoding, but VLPFC activation predicted successful
      memory for both associations and items. These results support the view that the
      DLPFC may contribute to LTM through its role in active processing of
      relationships during encoding, whereas the VLPFC may have a more general role in
      promoting successful LTM formation.

PMID- 17507574
TI  - Phosphatidylinositol-4,5-bisphosphate regulates NMDA receptor activity through
      alpha-actinin.
AB  - Phosphatidylinositol-4,5-bisphosphate (PIP2) has been shown to regulate many ion
      channels, transporters, and other signaling proteins, but it is not known whether
      it also regulates neurotransmitter-gated channels. The NMDA receptors (NMDARs)
      are gated by glutamate and serve as a critical control point in synaptic
      function. Here we demonstrate that PIP2 supports NMDAR activity. In Xenopus
      oocytes, overexpression of phospholipase Cgamma (PLCgamma) or preincubation with
      10 microm wortmannin markedly reduced NMDA currents. Stimulation of the epidermal
      growth factor receptor (EGFR) promoted the formation of an immunocomplex between
      PLCgamma and NMDAR subunits. Stimulation of EGFR or the PLCbeta-coupled M1
      acetylcholine receptor produced a robust transient inhibition of NMDA currents.
      Wortmannin application blocked the recovery of NMDA currents from the inhibition.
      Using mutagenesis, we identified the structural elements on NMDAR intracellular
      tails that transduce the receptor-mediated inhibition, which pinpoint to the
      binding site for the cytoskeletal protein alpha-actinin. Mutation of the PIP2
      binding residues of alpha-actinin dramatically reduced NMDA currents and occluded
      the effect of EGF. Interestingly, EGF or wortmannin affected the interaction
      between NMDAR subunits and alpha-actinin, suggesting that this protein mediates
      the effect of PIP2 on NMDARs. In mature hippocampal neurons, expression of the
      mutant alpha-actinin reduced NMDA currents and accelerated inactivation. We
      propose a model in which alpha-actinin supports NMDAR activity via tethering
      their intracellular tails to plasma membrane PIP2. Thus, our results extend the
      influence of PIP2 to the NMDA ionotropic glutamate receptors and introduce a
      novel mechanism of "indirect" regulation of transmembrane protein activity by
      PIP2.

PMID- 17507575
TI  - A child with primary Sjogren syndrome and a review of the literature.
AB  - Primary Sjogren syndrome (pSS) is an uncommon disease in childhood. Childhood pSS
      might have different clinical manifestations than adult pSS. We describe a 13
      year-old girl with multiple episodes of bilateral parotid swelling lasting 2
      years. Her history included severe arthralgia, local edema, and purpura episodes
      since 9 years of age. During her 3-week hospitalization, 2 episodes of parotid
      swelling occurred, which both resolved in 48 hours. Ultrasonography and magnetic
      resonance images of parotid glands showed parenchymal inhomogeneity related to
      adipose degeneration and nodular pattern. Investigations showed elevated
      erythrocyte sedimentation rate, the presence of hypergammaglobulinemia, positive
      antinuclear antibody, and elevated rheumatoid factor, anti-Sjogren syndrome
      antigen A, and anti-Sjogren syndrome antigen B. Histopathologic examination of
      labial minor salivary glands revealed focal periductal lymphocytic infiltrate and
      sialoduct ectasia. She was diagnosed as having pSS. Recurrent parotid swelling is
      a more characteristic feature of disease in children, and this finding should
      alert the clinician to the possible diagnosis of pSS.

PMID- 17507576
TI  - Leydig cell steroidogenesis: unmasking the functional importance of mitochondria.

PMID- 17507577
TI  - How low can maternal thyroxin go?

PMID- 17507578
TI  - G protein-coupled receptors and insulin secretion: 119 and counting.

PMID- 17507579
TI  - Hypogonadal bone loss: sex steroids or gonadotropins?

PMID- 17507581
TI  - Effect of motor practice on dual-task performance in older adults.
AB  - The aim of this study was to determine the effects of motor practice on cognitive
      and motor performance in older adults under single- and dual-task conditions.
      Fourteen younger (19-28 years) and 12 older adults (67-75 years) performed a
      precision grip sine wave force-tracking and a working memory task under single-
      and dual-task conditions. Participants performed a pretest, 100 motor practice
      trials, and a post-test. In the force-tracking and cognitive task, young
      outperformed older adults. Motor practice improved force-tracking under single-
      and dual-task conditions for both groups. However, practice did not prevent a
      decline in motor performance for older adults when they moved from single- to
      dual-task conditions. After practice, older adults improved cognitive performance
      in dual-task conditions. Advances in age appear to be associated with a decrease
      in the ability to manage and coordinate multiple tasks, which remains after
      extended practice.

PMID- 17507582
TI  - Moderation of older adults' retrieval reluctance through task instructions and
      monetary incentives.
AB  - Previous research using a noun-pair lookup task indicates that older adults delay
      strategy shift from visual scanning to memory retrieval despite adequate
      learning, and that this "retrieval reluctance" is related to subjective choice
      factors. Age differences in spontaneous response criteria, with older adults
      valuing accuracy and young adults valuing speed, might account for this
      phenomenon. The present experiment manipulates instructions and reward
      contingencies to test the flexibility of response criteria and strategy
      preferences. Task instructions conditions equally focused on speed and accuracy,
      encouraged retrieval use as a method toward fast responding, or offered monetary
      incentives for fast retrieval-based performance. Results indicate that older
      adults in the incentives condition shifted to retrieval earlier than those
      without incentives, bolstering the argument that reliance on retrieval is
      volitional.

PMID- 17507583
TI  - Longitudinal findings on aging-related cognitions, control beliefs, and health in
      later life.
AB  - We examined the influence of individual views of aging on health changes in later
      life. We hypothesized that aging-related cognitions affect health changes
      irrespective of control beliefs and that the impact of aging-related cognitions
      on health is higher than for the reverse direction of causality. We based our
      analyses on data from the longitudinal part of the German Aging Survey (N =
      1,286; participants were 40-85 years of age at baseline). Because of the
      selectivity of the sample, we also computed the same analyses for the baseline
      sample (N = 4,034) with estimated Time 2 data for those individuals who dropped
      out. The results of structural equation modeling were concordant with our
      hypotheses, and therefore they corroborate previous findings on the importance of
      beliefs about aging.

PMID- 17507584
TI  - Parental practices and willingness to ask for children's help later in life.
AB  - We examine how parents' relationships with their 13- to 25-year-old offspring
      affect the parents' willingness to ask them for help with financial and personal
      problems 20 years later. Husbands and wives were interviewed in 1974 and 1994; a
      child was interviewed in 1974. We used two aspects of parental style,
      responsiveness and restrictive dominance, to predict parents' willingness to
      request help from a child 20 years later. Structural equation modeling analyses
      revealed the following: (a) mothers' willingness to ask an adult child for help
      with a personal problem was increased by higher levels of responsiveness; (b)
      mothers' willingness to ask for financial help was increased by responsive and
      decreased by restrictive-dominant maternal behavior; and (c) neither responsive
      nor restrictive-dominant paternal behavior affected fathers' later willingness to
      ask an adult child for help of either kind.

PMID- 17507585
TI  - Effects of balance status and age on muscle activation while walking under
      divided attention.
AB  - We examined the role of attention during different phases of the gait cycle by
      using a dual-task paradigm. Younger and older adults performed a self-paced
      treadmill walking task, a semantic judgment task, and both tasks simultaneously.
      We recorded vocal reaction time for the judgment task, and we recorded muscle
      activity by the use of electromyography. We derived dual-task costs from
      difference scores (single vs dual task). Our analysis of the judgment task showed
      that both groups responded more quickly during dual-task conditions than during
      single-task conditions. In five of eight muscle groups, stance-phase muscle
      activity decreased significantly from dual to single task. For older adults,
      individuals with poor balance increased their muscle activity during dual-task
      performance. These results suggest that, during moderately demanding walking and
      cognitive performance, poor balancers can compensate successfully for their
      motoric vulnerability.

PMID- 17507586
TI  - Effects of cognitive training on change in accuracy in inductive reasoning
      ability.
AB  - We investigated cognitive training effects on accuracy and number of items
      attempted in inductive reasoning performance in a sample of 335 older
      participants (M = 72.78 years) from the Seattle Longitudinal Study. We assessed
      the impact of individual characteristics, including chronic disease. The
      reasoning training group showed significantly greater gain in accuracy and number
      of attempted items than did the comparison group; gain was primarily due to
      enhanced accuracy. Reasoning training effects involved a complex interaction of
      gender, prior cognitive status, and chronic disease. Women with prior decline on
      reasoning but no heart disease showed the greatest accuracy increase. In
      addition, stable reasoning-trained women with heart disease demonstrated
      significant accuracy gain. Comorbidity was associated with less change in
      accuracy. The results support the effectiveness of cognitive training on
      improving the accuracy of reasoning performance.

PMID- 17507587
TI  - Executive functions in normal aging: an examination of script sequencing, script
      sorting, and script monitoring.
AB  - We explored the effect of age on executive functions by using script-sequencing
      and script-sorting tasks. Older participants (n = 39), relative to young subjects
      (n = 40), committed more errors in script sequencing. However, there was no
      difference in performance between elderly and young subjects in excluding
      irrelevant items. These results suggest that aging generates impairment in the
      ability to produce temporally coherent sequences without deficit in the ability
      to eliminate distractors in the action domain. We proposed that the sequencing
      difficulties in elderly participants could be due to working-memory and shifting
      deficits mediated by changes in the dorsolateral prefrontal cortex.

PMID- 17507588
TI  - Performance on the Benton Visual Retention Test in an educationally diverse
      elderly population.
AB  - In this study, we investigated the effects of demographic variables on the
      performances of Administrations A and C of the Benton Visual Retention Test
      (BVRT) in a geriatric population with a wide range of educational achievement. We
      administered the test to 554 nondemented elders aged 60-90 years with an
      educational history of from zero to 25 years. Age and education significantly
      influenced Administrations A and C, although gender had no main effect. We
      observed significant Education x Gender interactions for Administrations A and C,
      Age x Gender interactions for Administration A, and Age x Education interactions
      for Administration C. Our results suggest that both nonverbal memory and
      constructional ability are influenced by age and education. Although there is no
      overall gender effect, men seem to outperform women in a poorly educated (for
      Administrations A and C) or relatively older (for Administration A) elderly
      population.

PMID- 17507589
TI  - Aging and memory for numerical information: the role of specificity and expertise
      in associative memory.
AB  - In order to examine the nature of associative memory deficits in old age, the
      present study examined how younger and older adults link numerical and object
      information to other items. The hypothesis was that there would be large age
      differences for numerical information caused by the arbitrariness and specificity
      of this type of information, but that this could be reduced by expertise.
      Participants studied sentences that contained numeric quantity, object, and
      location information (e.g., 26 cherries in the bowl); they were later cued with
      the location and had to recall the object and quantity. In general, there were
      significant age differences for quantity recall but negligible age differences
      for recall of related objects but not unrelated objects. However, a group of
      older retired accountants and bookkeepers showed exceptional memory for quantity
      information. The findings suggest that the associative deficit in old age is
      based on the linking of specific arbitrary information.

PMID- 17507590
TI  - Scales and tales: older women's difficulty with daily tasks.
AB  - OBJECTIVES: Part of a 3-year study of the home care experience among 25 older
      women (aged 80-96), this research aimed to describe how the women understood
      difficulty relative to 20 basic and instrumental activity of daily living tasks.
      METHODS: This was a qualitative study with a quantitative component. During open
      ended interviews about living alone with help, participants rated difficulty with
      tasks on a 1-to-5 scale and talked about difficulty relative to tasks. I
      estimated concordance of the first two ratings and used a descriptive
      phenomenological method to discern how participants understood difficulty.
      RESULTS: Concordance was satisfactory for all tasks other than climbing stairs.
      Six elements of the life-world of older women were descriptive of difficulty
      relative to tasks, including pinpointing my biggest/hardest job and having
      difficulty rating difficulty. Whether reporting difficulty or not, some women
      spoke of taking extra time, extra effort, or both. DISCUSSION: The findings
      suggest a counterview to functional limitation models. Difficulty was posed as a
      theoretical construct, and the concept of subliminal difficulty was introduced.
      Various facets of difficulty warrant further descriptive work. Incorporating an
      opportunity to talk about difficulty, as well as to rate it, would be valuable in
      large-scale studies.

PMID- 17507591
TI  - An interpersonal continuity of care measure for Medicare Part B claims analyses.
AB  - OBJECTIVES: This article presents an interpersonal continuity of care measure.
      METHODS: We operationalized continuity of care as no more than an 8-month
      interval between any two visits during a 2-year period to either (a) the same
      primary care physician or (b) the same physician regardless of specialty.
      Sensitivity analyses evaluated two interval censoring algorithms and two
      alternative intervals. We linked Medicare Part A and B claims to baseline survey
      data for 4,596 respondents to the Survey on Asset and Health Dynamics Among the
      Oldest Old. We addressed the potential for selection bias by using propensity
      score methods, and we explored construct validity. RESULTS: Interpersonal
      continuity with a primary care physician was 17.3%, and interpersonal continuity
      of care with any physician was 26.1%. Older participants; men; individuals who
      lived alone; people who had difficulty walking; and respondents with medical
      histories of arthritis, cancer, diabetes, heart conditions, hypertension, and
      stroke were most likely to have continuity. Individuals who had never married,
      were widowed, were working, or had low subjective life expectancy were least
      likely to have continuity. DISCUSSION: Researchers can measure interpersonal
      continuity of care using Medicare Part B claims. Replication of these findings
      and further construct validation, however, are needed prior to widespread
      adoption of this method.

PMID- 17507592
TI  - Risk of nursing home admission among older americans: does states' spending on
      home- and community-based services matter?
AB  - OBJECTIVE: States vary greatly in their support for home- and community-based
      services (HCBS) that are intended to help disabled seniors live in the community.
      This article examines how states' generosity in providing HCBS affects the risk
      of nursing home admission among older Americans and how family availability
      moderates such effects. METHODS: We conducted discrete time survival analysis of
      first long-term (90 or more days) nursing home admissions that occurred between
      1995 and 2002, using Health and Retirement Study panel data from respondents born
      in 1923 or earlier. RESULT: State HCBS effects were conditional on child
      availability among older Americans. Living in a state with higher HCBS
      expenditures was associated with lower risk of nursing home admission among
      childless seniors (p <.001). However, the association was not statistically
      significant among seniors with living children. Doubling state HCBS expenditures
      per person aged 65 or older would reduce the risk of nursing home admission among
      childless seniors by 35%. DISCUSSION: Results provided modest but important
      evidence supportive of increasing state investment in HCBS. Within-state
      allocation of HCBS resources, however, requires further research and careful
      consideration about fairness for individual seniors and their families as well as
      cost effectiveness.

PMID- 17507593
TI  - Sekentei and family caregiving of elders among the Japanese: development and
      psychometric evaluation of the sekentei scale.
AB  - OBJECTIVES: This study describes the development and psychometric evaluation of a
      measure for assessing sekentei, a construct rooted in the Japanese culture.
      Sekentei is a social construct that causes a person to worry about others'
      evaluations of his or her behavior. The concept of sekentei may be an important
      factor related to family caregiving of elders in Japan. METHODS: We used a
      multiphased process to develop, refine, and evaluate the reliability and validity
      of the Sekentei Scale. Following the development and refinement of the measure,
      we administered the Sekentei Scale and other measures for assessing validity to
      150 Japanese National and 116 Caucasian American family caregivers of elders. We
      used Cronbach's alpha to estimate internal consistency reliability. We examined
      validity by (a) correlating scores on the Sekentei and Shame Scales and (b)
      testing the Sekentei Scale's ability to yield hypothesized differences between
      the Japanese and the Americans. RESULTS: The results provided adequate support
      for the reliability and validity of the Sekentei Scale. DISCUSSION: The findings
      provide useful data regarding the construct and measurement of sekentei and
      provide preliminary psychometric support for the measure's use in future
      research.

PMID- 17507594
TI  - Socioeconomic differences in mortality among U.S. adults: insights into the
      Hispanic paradox.
AB  - OBJECTIVES: This study examined socioeconomic differentials in mortality among
      Hispanics in the United States, focusing on the older ages. We address previous
      research suggesting that social disparities in health are smaller for Hispanics
      than for non-Hispanic Whites and examine whether these differentials in survival
      are related to the mortality advantage that characterizes the older Hispanic
      population (i.e., the Hispanic paradox). METHODS: We used Poisson regression
      models based on data from the 1989 to 1994 waves of the National Health Interview
      Survey, with linked mortality through 1997, to estimate death rates for Hispanics
      and non-Hispanic Whites by age, gender, and socioeconomic status. RESULTS: Deaths
      rates varied significantly (p <.05) by education and income for Whites and
      Hispanic subgroups defined by nativity (U.S. born and foreign born) and
      nationality (Mexican, Puerto Rican, and other Hispanic). However, with the
      exception of Puerto Ricans, the effects of education were significantly smaller
      for Hispanics than for Whites. The ethnic differences in mortality patterns by
      income were not statistically significant. DISCUSSION: The findings reveal that
      the mortality advantage for Hispanics is concentrated at lower levels of
      socioeconomic status, with little or no advantage at higher levels. We propose
      several mechanisms related to immigration and assimilation patterns that may
      underlie these patterns of mortality.

PMID- 17507595
TI  - Educational disparities in the prevalence and consequence of physical
      vulnerability.
AB  - OBJECTIVES: The purpose of this study was to estimate educational differences in
      the prevalence and mortality consequence of physical vulnerability among older
      adults in the United States. METHODS: Data came from the 1998 and 2000 waves of
      the Health and Retirement Study, a nationally representative cross-sectional and
      prospective cohort study of community-based adults aged 65 and older. We created
      a physical vulnerability score from age, gender, and self-reported disability
      measures and measured socioeconomic status via educational attainment. Mortality
      data came from the National Death Index. RESULTS: In the 1998 cohort, high
      physical vulnerability was more than 3 times more prevalent in individuals with
      less than 12 years of education compared to those with 16 or more years of
      education. Although less educated older adults had a higher probability of death
      overall, evidence of educational differences in the mortality consequence of high
      physical vulnerability was limited. In 2000, 2.16 million older adults had high
      physical vulnerability, and more than one half (53%) of these adults had less
      than 12 years of education. DISCUSSION: In persons 65 years of age or older,
      educational differences are more apparent in the prevalence of physical
      vulnerability than in the mortality consequence of that vulnerability.

PMID- 17507596
TI  - Aging and the elapse of time: a comment on the analysis of change.

PMID- 17507597
TI  - Age versus time since baseline as the time scale in the analysis of change.

PMID- 17507598
TI  - Arsenic trioxide inhibits growth of As4.1 juxtaglomerular cells via cell cycle
      arrest and caspase-independent apoptosis.
AB  - We investigated the in vitro effects of arsenic trioxide on cell growth, cell
      cycle regulation, and apoptosis in As4.1 juxtaglomerular cells. Arsenic trioxide
      inhibited the growth of As4.1 cells with an IC(50) of approximately 5 microM.
      Arsenic trioxide induced S phase arrest of the cell cycle and very efficiently
      stimulated apoptosis in As4.1 cells, as evidenced by flow cytometric detection of
      sub-G(1) DNA content, annexin V binding assay, and 4'-6-diamidino-2-phenylindole
      staining. This apoptotic process was accompanied by the loss of mitochondrial
      transmembrane potential (DeltaPsi(m)), a decrease in Bcl-2, the activation of
      caspase-3, and cleavage of poly(ADP-ribose) polymerase. However, all of the
      caspase inhibitors tested in this experiment failed to rescue As4.1 cells from
      arsenic trioxide-induced cell death in view of sub-G(1) cells and annexin V
      positive-staining cells. However, a caspase-8 inhibitor (Z-IETD-FMK) noticeably
      decreased the loss of DeltaPsi(m) in arsenic trioxide-treated cells. When we
      examined the changes in reactive oxygen species (ROS), H(2)O(2), or O(2)(*-) in
      arsenic trioxide-treated cells, H(2)O(2) was significantly decreased and O(2)(*-)
      was increased. In addition, we detected a decreased GSH content in arsenic
      trioxide-treated cells. Taken together, we have demonstrated that arsenic
      trioxide as a ROS generator potently inhibited the growth of As4.1 JG cells
      through S phase arrest of the cell cycle and caspase-independent apoptosis.

PMID- 17507599
TI  - Recovery from acute renal failure predisposes hypertension and secondary renal
      disease in response to elevated sodium.
AB  - Recovery of renal function is a well-characterized feature of models of acute
      renal failure; however, more recent studies have reported a predisposition to
      chronic renal disease. This study sought to determine the susceptibility to
      sodium-dependent hypertension following recovery from ischemic acute renal
      failure. Following ischemia-reperfusion (I/R) injury, rats were allowed to
      recover for 35 days on a 0.4% salt diet, then were switched to 4.0% salt diet for
      an additional 28 days. Blood pressure was significantly increased in postischemic
      rats switched to high-sodium diet at day 35 (19 +/- 9 mmHg) compared with
      postischemic rats maintained on low-sodium diet. Plasma renin activity and
      creatinine clearance were not affected by I/R injury. The ischemic injury
      combined with transfer to 4.0% salt diet resulted in marked renal hypertrophy
      characterized by interstitial cellular deposition, tubular dilation, and enhanced
      rates of albumin excretion. Glomerular structure was altered in post-I/R rats
      switched to high-sodium diet but not in those maintained on low-sodium diets.
      When rats were acclimated to high-sodium diet before I/R injury, the early injury
      was similar to that observed in animals acclimated to low-sodium diet, and these
      animals progressed rapidly toward chronic kidney disease, as evidenced by
      advancement of albuminuria. These data suggest that the recovery from acute I/R
      injury is not complete, compromises Na homeostasis, and predisposes hypertension
      and secondary renal disease.

PMID- 17507600
TI  - Subclinical kidney injury incites endotoxin hyperresponsiveness.

PMID- 17507601
TI  - How to keep kidneys safe while shrinking tumors: the conundrum of cisplatin
      action.

PMID- 17507602
TI  - Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the
      glomerular protein permeability barrier.
AB  - This study examined the metabolism of arachidonic acid (AA) by cytochrome P-450
      enzymes in isolated glomeruli and the effects of selective inhibitors of the
      synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatetraenoic
      acids (EETs) on glomerular permeability to albumin (P(alb)). Glomeruli avidly
      produced 20-HETE, EETs, dihydroxyeicosatetraenoic acids (diHETEs), and HETEs when
      incubated with exogenous AA. N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine
      (HET0016; 10 microM) selectively inhibited the formation of 20-HETE by 95% and
      increased P(alb) from 0.00 +/- 0.08 to 0.73 +/- 0.10 (n = 43 glomeruli, 4 rats).
      Addition of a 20-HETE mimetic, 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (20-5,14
      HEDE; 1 microM) opposed the effects of HET0016 (10 microM) to increase P(alb)
      (0.21 +/- 0.10, n = 36 glomeruli, 4 rats). Preincubation of glomeruli with
      exogenous AA to increase basal production of 20-HETE had a similar effect. We
      also examined the effect of an epoxygenase inhibitor, N-methylsulfonyl-6-(2
      propargyloxyphenyl)hexanamide (MSPPOH; 5 microM), on P(alb). MSPPOH (5 microM)
      significantly increased P(alb) but had no effect on the synthesis of EETs in
      glomeruli incubated with AA. However, MSPPOH (5 microM) selectively reduced
      epoxygenase activity by 50% in glomeruli incubated without added AA. Pretreatment
      with 8,9-EET (100 nM) attenuated the effects of MSPPOH (5 microM) on P(alb).
      These results indicate that glomeruli produce 20-HETE, EETs, diHETEs, and HETEs
      and that endogenously formed 20-HETE and EETs play an essential role in the
      maintenance of the glomerular permeability barrier to albumin.

PMID- 17507603
TI  - ANG II provokes acute trafficking of distal tubule Na+-Cl(-) cotransporter to
      apical membrane.
AB  - The distal convoluted tubule (DCT) Na+-Cl(-) cotransporter (NCC), the target of
      thiazide diuretics, is responsible for the reabsorption of 5-10% of filtered
      NaCl. The aim of this study was to test the hypothesis that acute infusion of the
      angiotensin-converting enzyme (ACE) inhibitor captopril (at 12 microg/min) for 20
      min provokes trafficking of NCC from apical plasma membranes (APM) to subapical
      cytoplasmic vesicles (SCV), which is reversed by acute ANG II infusion (ANG II at
      20 ng.kg(-1).min(-1) along with 12 microg/min captopril) for 20 min in male
      Sprague-Dawley rats (250-350 g). By immuno-electron microscopy using an anti-NCC
      (D. Ellison) 71.5 +/- SD 4.9% of the NCC gold labeling was associated with the
      APM in control, sham operated, and infused rats, while captopril infusion reduced
      NCC in APM to 54.9 +/- 6.9% (P < 0.001) and markedly increased immunogold
      labeling of SCV. Subsequent infusion of ANG II with captopril restored NCC
      immunogold labeling of APM to 72.4 +/- 4.2%, that is, 20% of the total NCC
      trafficked between APM and SCV. Likewise, on density gradients of cortex,
      captopril provoked redistribution of 27.3% of total NCC from low-density APM
      enriched membranes to higher-density membranes and ANG II+captopril restored
      20.3% of the NCC to APM-enriched fractions. Redistribution occurred independent
      of a change in NCC total abundance. In conclusion, this study demonstrates that
      ACE inhibition provokes acute trafficking of NCC out of the plasma membrane,
      which likely decreases DCT Na+ reabsorption, while ANG II provokes rapid
      trafficking of NCC from stores in subapical vesicles to the plasma membrane,
      which likely increases DCT Na+ reabsorption.

PMID- 17507604
TI  - Vasopressin-induced nitric oxide production in rat inner medullary collecting
      duct is dependent on V2 receptor activation of the phosphoinositide pathway.
AB  - We previously reported that arginine vasopressin (AVP) stimulates the production
      of nitric oxide (NO) in inner medullary collecting duct (IMCD) via activation of
      V2 receptors (V2R) and the mobilization of intracellular Ca(2+). The aim of this
      study was to determine the pathway(s) through which this response is mediated.
      IMCDs were dissected from male Sprague-Dawley rats and intracellular Ca(2+)
      concentration ([Ca(2+)](i)) and NO production were measured using a fluorescence
      imaging system. AVP (100 nmol/l) produced a rapid increase [Ca(2+)](i) of 381 +/-
      78 nmol/l that was followed by a significant increase of NO production (166 +/-
      61%). The specific nonpeptide V2R antagonist OPC31260 (1 microM), but not the V1R
      antagonist OPC21268 (1 microM), inhibited the increase in [Ca(2+)](i) (up to 91
      +/- 5%) and abolished the NO response to AVP. Both the phospholipase C inhibitor
      U73112 (3 microM) and the inositol (1,4,5) tri-phosphate 3 receptor blocker 2-APB
      (75 microM) reduced the peak [Ca(2+)](i) response to AVP (by 65 +/- 9 and 59 +/-
      15%, respectively) and abolished the NO response. Although forskolin (100 microM;
      an activator of adenylyl cyclase) elicited a moderate increase in [Ca(2+)](i),
      neither preincubation with the adenylyl cyclase inhibitor 2'-5'-dideoxyadenosine
      (50 microM) nor the protein kinase A (PKA) inhibitor PKA(14-22) (100 microM)
      significantly inhibited peak [Ca(2+)](i) in response to AVP. IMCD [Ca(2+)](i)
      responses to AVP were reduced by 72 +/- 8% when incubated in Ca(2+)-free media
      and could be completely abolished by preincubation with the Ca(2+)-ATPase
      inhibitor thapsigargin. We conclude that AVP-induced NO production in IMCD is
      dependent on V2R activation of the phosphoinositide pathway and the mobilization
      of Ca(2+) from both intracellular and extracellular pools.

PMID- 17507606
TI  - Genetic association studies of cancer: where do we go from here?

PMID- 17507605
TI  - Building a united front: aligning the agendas for tobacco control, lung cancer
      research, and policy.
AB  - Our society bears a tremendous public health burden from tobacco-related
      disability and death, particularly in the realm of cancer. Yet research in lung
      cancer and other tobacco-related diseases research is dramatically underfunded
      when compared to the number of people affected. Persuading policy makers to
      increase funding for tobacco-related research, treatment, and policy initiatives
      will require considerable cooperation among the researchers, clinicians, and
      advocates who focus on tobacco control and those who concentrate on tobacco
      related disease. Traditionally, these groups have battled over resources,
      expending precious energy competing for scarce funding. We propose a new way
      forward: these forces should come together in support of a common agenda that
      includes both increased tobacco control efforts and additional funding for
      disease-related research and treatment. Speaking with a unified voice in support
      of a full continuum of tobacco-related policy initiatives would significantly
      increase the size and influence of the coalition working to address this public
      health epidemic. Working together offers our nation the best chance of
      significantly reducing the scourge of disease and death caused by tobacco use.

PMID- 17507607
TI  - The intersection of cancer and aging: establishing the need for breast cancer
      rehabilitation.
AB  - The increasing success of treatments for common cancers has resulted in growing
      awareness of the unique health care needs of cancer survivors. Cancer treatments
      can be toxic and have long-lasting effects on health, potentially accelerating
      the aging process and producing associated declines in physical function. In this
      synthesis of the literature, we critically examine the strength of existing
      evidence that breast cancer diagnosis and treatment are associated with a
      disproportionate decline in physical function compared with the effects of living
      without cancer for the same number of years. There is some observational
      epidemiologic evidence that women treated for breast cancer report greater
      declines in physical function than their peers. Discerning the factors associated
      with such declines and their clinical significance remains to be addressed.
      Physiologic, psychological, and behavioral changes associated with both aging and
      cancer treatment are reviewed. Parallels are proposed between existing preventive
      and rehabilitative programs and possibilities for similar interventions aimed at
      preventing, reversing, or halting declines in physical function in cancer
      survivors. Finally, a program of research is proposed to evaluate whether there
      is some subset of breast cancer survivors for whom prevention or rehabilitation
      of functional status declines is needed, as well as development of targeted,
      mechanistically driven interventions.

PMID- 17507608
TI  - Gut check: can cost-effectiveness analysis help eliminate gastric cancer in Asia?

PMID- 17507609
TI  - Cost-effectiveness analysis between primary and secondary preventive strategies
      for gastric cancer.
AB  - OBJECTIVE: The present study is done to assess the relative cost-effectiveness,
      optimal initial age, and interscreening interval between primary and secondary
      prevention strategies for gastric cancer. METHODS: Base-case estimates, including
      variables of natural history, efficacy of intervention, and relevant cost, were
      derived from two preventive programs targeting a high-risk population. Cost
      effectiveness was compared between chemoprevention with (13)C urea breath testing
      followed by Helicobacter pylori (H. pylori) eradication and high-risk
      surveillance based on serum pepsinogen measurement and confirmed by endoscopy.
      The main outcome measure was cost per life-year gained with a 3% annual discount
      rate. RESULTS: The incremental cost-effectiveness ratio (ICER) for once-only
      chemoprevention at age 30 years versus no screening was U.S. $17,044 per life
      year gained. Eradication of H. pylori at later age or with a periodic scheme
      yielded a less favorable result. Annual high-risk screening at age of 50 years
      versus no screening resulted in an ICER of U.S. $29,741 per life-year gained. The
      ICERs of surveillance did not substantially vary with different initial ages or
      interscreening intervals. Chemoprevention could be dominated by high-risk
      surveillance when the initial age was older than 44 years. Otherwise,
      chemoprevention was more cost-effective than high-risk surveillance, either at
      ceiling ratios of U.S. $15,762 or up to U.S. $50,000. The relative cost
      effectiveness was most sensitive to the infection rate of H. pylori and
      proportion of early gastric cancer in all detectable cases. CONCLUSIONS: Early H.
      pylori eradication once in lifetime seems more cost-effective than surveillance
      strategy. However, the choice is still subject to the risk of infection,
      detectability of early gastric cancer, and timing of intervention.

PMID- 17507610
TI  - Evaluation of matrix metalloproteinase 7 in plasma and pancreatic juice as a
      biomarker for pancreatic cancer.
AB  - Differentiating between periampullary carcinoma and chronic pancreatitis with an
      inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections
      for suspected carcinoma are done inappropriately for chronic pancreatitis. Here,
      we test if matrix metalloproteinase 7 (MMP-7), a secreted protease frequently
      expressed in pancreatic carcinoma, can be measured in plasma, pancreatic, and
      duodenal juice, and if it can distinguish between periampullary carcinoma and
      chronic pancreatitis. Ninety-four patients who underwent pancreatic surgery for a
      (peri)pancreatic neoplasm (n = 63) or chronic pancreatitis (n = 31) were
      analyzed. Median plasma MMP-7 levels were significantly higher in carcinoma (1.95
      ng/mL; interquartile range, 0.81-3.22 ng/mL) compared with chronic pancreatitis
      and benign disease (0.83 ng/mL; interquartile range, 0.25-1.21 ng/mL; P < 0.01).
      MMP-7 levels in pancreatic juice were higher, although not significantly, in
      carcinoma (62 ng/mg protein; interquartile range, 18-241 ng/mg protein) compared
      with chronic pancreatitis and benign disease (23 ng/mg protein; interquartile
      range, 8.5-99 ng/mg protein; P = 0.17). MMP-7 levels in duodenal juice were
      universally low. At an arbitrary cutoff of 1.5 ng/mL in plasma, positive and
      negative predictive values were 83% and 57%, respectively, values comparable to
      those of today's most common pancreatic tumor marker, carbohydrate antigen 19-9
      (CA19-9; 83% and 53%, respectively). Positive and negative likelihood ratios for
      plasma MMP-7 were 3.35 and 0.52, respectively. The area under the receiver
      operating characteristic curve for MMP-7 was 0.73 (95% confidence interval, 0.63
      0.84) and for CA19-9, 0.75 (95% confidence interval, 0.64-0.85). Combined MMP-7
      and CA19-9 assessment gave a positive predictive value of 100%. Thus, plasma MMP
      7 levels discriminated between patients with carcinoma and those with chronic
      pancreatitis or benign disease. The diagnostic accuracy of plasma MMP-7 alone is
      not sufficient to determine treatment strategy in patients with a periampullary
      mass, but combined evaluation of plasma MMP-7 with CA19-9 and other markers may
      be clinically useful.

PMID- 17507611
TI  - Is TGFBR1*6A a susceptibility allele for nonsyndromic familial colorectal
      neoplasia?
AB  - Our analysis definitely excludes the possibility of the TGFBR1*6A allele
      increasing the risk of colorectal neoplasia in our sample population. A recent
      study validating linkage of colorectal cancer to chromosome 9q also excluded the
      TGFBR1*6A allele as a disease-causing variant in that sample. We conclude that
      there remains an unidentified susceptibility locus in the region 9q22.2-31.2.

PMID- 17507612
TI  - Effect of a 12-month randomized clinical trial of exercise on serum prolactin
      concentrations in postmenopausal women.
AB  - Prolactin is associated with an increased risk of postmenopausal breast cancer;
      however, few modifiable factors are known to reduce prolactin concentrations.
      Therefore, we examined the effect of a 12-month moderate-intensity exercise
      intervention on serum prolactin concentrations as a secondary end point (primary
      end points were estrogens and androgens). We randomly assigned 173 postmenopausal
      women who were sedentary, overweight (body mass index >24 kg/m(2), body fat
      >33%), ages 50 to 75 years, and not using hormone therapy to an exercise
      intervention or stretching control group. The intervention was facility- and home
      based (45 min, 5 days/wk moderate-intensity sports/recreational exercise). One
      hundred and seventy (98%) women completed the study. Prolactin concentrations
      were similar at baseline (P = 0.25, geometric mean exercisers = 6.9 and controls
      = 7.5 ng/mL). Overall, the intervention was not associated with changes in
      prolactin concentrations between exercisers and controls at 3 months (P = 0.46)
      or 12 months (P = 0.29). The intervention effect did not vary by baseline age,
      body mass index, parity, or change in percent body fat during the intervention.
      Among exercisers, there was a significant difference in prolactin concentrations
      by change in fitness (VO(2)max) between baseline and 12 months. Exercisers whose
      VO(2)max changed by <5% had a 5% increase in prolactin concentrations, whereas
      those who increased their VO(2)max by 5% to 15% and >15% had a 11% (P = 0.03) and
      7% (P = 0.01) decrease in prolactin concentrations, respectively. Although the
      exercise intervention had little effect on prolactin concentrations overall,
      increasing physical fitness was associated with reduced prolactin concentrations
      among postmenopausal women.

PMID- 17507613
TI  - Usual physical activity and endogenous sex hormones in postmenopausal women: the
      European prospective investigation into cancer-norfolk population study.
AB  - BACKGROUND: Short-term trials indicate that intensive physical activity may
      influence endogenous sex hormone concentrations. However, the relationship
      between usual daily physical activity and endogenous hormones in postmenopausal
      women in the general population is still uncertain. OBJECTIVE AND METHODS: To
      determine the relationship between usual physical activity and endogenous sex
      hormones in postmenopausal women. A cross-sectional population-based study of
      2,082 postmenopausal women ages 55 to 81 years, residing in the general community
      of Norfolk, United Kingdom, and not currently using hormone replacement therapy
      were chosen to participate. Physical activity in the past 1 year was assessed
      using a validated questionnaire, and endogenous sex hormone and sex hormone
      binding globulin (SHBG) concentrations were determined. RESULTS: Usual physical
      activity levels were inversely associated with circulating concentrations of
      testosterone and estradiol, testosterone/SHBG ratio, and positively associated
      with SHBG. These associations were only slightly attenuated after adjusting for
      potential covariates including body mass index, smoking status, alcohol intake,
      and reproductive variables. Testosterone concentrations and testosterone/SHBG
      ratios were 19% [95% confidence interval (95% CI), 9-27%, P < 0.001] and 24.0%
      (95% CI, 13-34% P < 0.001) lower, respectively, whereas estradiol concentrations
      were 6% (95% CI, 0-12%; P < 0.05) lower in the highest compared with lowest
      activity levels, respectively. A decreasing trend for the estradiol/SHBG ratio
      and 17alpha-hydroxyprogesterone concentrations was also observed. Androstenedione
      levels did not differ significantly according to physical activity. CONCLUSIONS:
      Higher usual physical activity levels among postmenopausal women seem to be
      related to lower endogenous testosterone and estradiol concentrations. This may
      be one mechanism that could partly explain the reported inverse relationship
      between physical activity and breast cancer risk in some studies.

PMID- 17507614
TI  - Reproductive history and risk of second primary breast cancer: the WECARE study.
AB  - BACKGROUND: Women with an initial breast cancer diagnosis are at elevated risk of
      developing subsequent cancer in the contralateral breast. Studies of reproductive
      factors and contralateral breast cancer (CBC) have provided inconsistent results.
      METHODS: We employed a case-control study nested within five population-based
      cancer registries in the United States and Denmark to examine associations
      between reproductive history and CBC risk. Cases were women with asynchronous CBC
      who had their first primary invasive breast cancer before age 55 years. Two
      controls, who had only one primary breast cancer diagnosis, were individually
      matched to each case on age and year of diagnosis, race, and registry. A total of
      694 case-control triplets and 11 case-control pairs were enrolled. Information
      regarding possible CBC risk factors was obtained via telephone interviews.
      Multivariable conditional logistic regression was used to estimate rate ratios
      (RR) and 95% confidence intervals (95% CI) associated with risk factors of
      interest. RESULTS: Increasing number of full-term pregnancies (FTP) was inversely
      associated with CBC risk (P trend, 0.001). Women who reported menarche before age
      13 years had an increased risk of CBC (RR, 1.26; 95% CI, 1.01-1.58). Age at first
      FTP, breastfeeding history, and age at menopause were not significantly
      associated with CBC risk. CONCLUSIONS: These results suggest age at menarche and
      parity, which are established risk factors for first primary breast cancer, are
      associated with CBC, whereas other reproductive risk factors associated with
      first primary breast cancer, such as age at first FTP, are less important factors
      in the development of CBC.

PMID- 17507615
TI  - The CYP1A2 genotype modifies the association between coffee consumption and
      breast cancer risk among BRCA1 mutation carriers.
AB  - We have recently reported that, among BRCA1 mutation carriers, the consumption of
      caffeinated coffee was associated with a significant reduction in breast cancer
      risk. Because the metabolism of caffeine is primarily by CYP1A2, we examined
      whether or not the CYP1A2 genotype modifies the association between a history of
      coffee consumption and the risk of breast cancer. A common A to C polymorphism in
      the CYP1A2 gene is associated with decreased enzyme inducibility and impaired
      caffeine metabolism. Information regarding coffee consumption habits and the
      CYP1A2 genotype was available for 411 BRCA1 mutation carriers (170 cases and 241
      controls). We estimated the odds ratios (ORs) and 95% confidence intervals (95%
      CIs) for breast cancer associated with the CYP1A2 genotype and a history of
      coffee consumption before age 35, adjusting for potential confounders. The CYP1A2
      genotype did not affect breast cancer risk. Among women with at least one variant
      C allele (AC or CC), those who consumed coffee had a 64% reduction in breast
      cancer risk, compared with women who never consumed coffee (OR, 0.36; 95% CI,
      0.18-0.73). A significant protective effect of coffee consumption was not
      observed among women with the CYP1A2 AA genotype (OR, 0.93; 95% CI, 0.49-1.77).
      Similar results were obtained when the analysis was restricted to caffeinated
      coffee. This study suggests that caffeine protects against breast cancer in women
      with a BRCA1 mutation and illustrates the importance of integrating individual
      genetic variability when assessing diet-disease associations.

PMID- 17507616
TI  - Expression of cytochrome P450 1B1 and catechol-O-methyltransferase in breast
      tissue and their associations with breast cancer risk.
AB  - Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are
      important estrogen-metabolizing enzymes that may affect breast cancer risk. Few
      studies have directly measured the expression of CYP1B1 and COMT genes in breast
      tissue samples. The subjects in this study were a subgroup of participants of the
      Shanghai Breast Cancer Study including 64 patients diagnosed with breast cancer
      and 68 patients diagnosed with benign breast diseases (BBD) who provided samples
      of tumor tissue and adjacent nontumor tissue to the study. We compared CYP1B1 and
      COMT mRNA expression in tumor tissue and adjacent nontumor tissue in both breast
      cancer patients and BBD patients. High levels of CYP1B1 expression and low levels
      of COMT expression in adjacent nontumor tissue were associated with a
      significantly increased breast cancer risk in a nonlinear manner. Odds ratios and
      95% confidence intervals (in parentheses) for the midpoints of the first, second,
      fourth, and fifth quintiles of gene expression levels compared with the overall
      median levels in BBD subjects were 0.21 (0.07-0.67), 0.81 (0.69-0.95), 1.20 (1.05
      1.38), and 1.55 (1.12-2.15) for CYP1B1 and 1.72 (1.17-2.55), 1.19 (1.05-1.35),
      0.83 (0.73-0.95), and 0.78 (0.65-0.93) for COMT, respectively. These results
      support the hypothesis that the formation and accumulation of catechol estrogens
      in breast tissue through increased CYP1B1 expression and reduced COMT expression
      may play a significant role in breast cancer risk.

PMID- 17507617
TI  - Longitudinal trends in mammographic percent density and breast cancer risk.
AB  - BACKGROUND: Mammographic density is a strong risk factor for breast cancer.
      However, whether changes in mammographic density are associated with risk remains
      unclear. MATERIALS AND METHODS: A study of 372 incident breast cancer cases and
      713 matched controls was conducted within the Mayo Clinic mammography screening
      practice. Controls were matched on age, exam date, residence, menopause, interval
      between, and number of mammograms. All serial craniocaudal mammograms 10 years
      before ascertainment were digitized, and quantitative measures of percent density
      (PD) were estimated using a thresholding method. Data on potential confounders
      were abstracted from medical records. Logistic regression models with generalized
      estimating equations were used to evaluate the interactions among PD at earliest
      mammogram, time from earliest to each serial mammogram, and absolute change in PD
      between the earliest and subsequent mammograms. Analyses were done separately for
      PD measures from the ipsilateral and contralateral breast and also by use of
      hormone therapy (HT). RESULTS: Subjects had an average of five mammograms
      available, were primarily postmenopausal (83%), and averaged 61 years at the
      earliest mammogram. Mean PD at earliest mammogram was higher for cases (31%) than
      controls (27%; ipsilateral side). There was no evidence of an association between
      change in PD and breast cancer risk by time. Compared with no change, an overall
      reduction of 10% PD (lowest quartile of change) was associated with an odds ratio
      of 0.9997 and an increase of 6.5% PD (highest quartile of change) with an odds
      ratio of 1.002. The same results held within the group of 220 cases and 340
      controls never using HT. Among the 124 cases and 337 controls known to use HT
      during the interval, there was a statistically significant interaction between
      change in PD and time since the earliest mammogram (P = 0.01). However, in all
      groups, the risk associated with the earliest PD remained a stronger predictor of
      risk than change in PD. CONCLUSION: We observed no association between change in
      PD with breast cancer risk among all women and those never using HT. However, the
      interaction between change in PD and time should be evaluated in other
      populations.

PMID- 17507618
TI  - Synchronized seasonal variations of mammographic breast density and plasma 25
      hydroxyvitamin d.
AB  - BACKGROUND: Dietary vitamin D has been associated with lower mammographic breast
      density, a strong biomarker for breast cancer risk. Blood 25-hydroxyvitamin D
      [25(OH)D] is an integrated measure of vitamin D status (from food, supplements,
      and sun exposure) and varies with season. Our objective was to assess seasonal
      variations of breast density and compare such variations, if any, with that of
      25(OH)D. METHODS: This cross-sectional study includes 741 premenopausal women
      recruited at screening mammography. Plasma 25(OH)D at recruitment was measured by
      RIA. Breast density was evaluated using a computer-assisted method. Seasonal
      variations were modeled using multivariate linear regression and semi-parametric
      cubic smoothing splines. RESULTS: Season was strongly associated with 25(OH)D (P
      < 0.0001). The highest smoothed mean 25(OH)D levels were seen at the end of July
      (81.5 nmol/L) and the lowest in mid-April (52.4 nmol/L). Breast density showed
      modest seasonal variations (P = 0.028). The lowest smoothed mean breast density
      was observed in early December (38.5%) and the highest at the beginning of April
      (44.3%). When a 4-month lag time was presumed, seasonal variations of breast
      density appeared to be a mirror image of those of 25(OH)D, and the correlation of
      daily smoothed estimates of mean breast density and 25(OH)D was negative and
      strong (r = -0.90). CONCLUSION: In premenopausal women, changes in blood vitamin
      D seem to be inversely related to changes in breast density with a lag time of
      about 4 months. This finding encourages further investigation of the possibility
      that vitamin D could reduce breast density and breast cancer risk.

PMID- 17507619
TI  - Recreational physical activity and mammographic breast density characteristics.
AB  - Increased mammographic breast density is considered an intermediate marker of
      breast cancer risk. Physical activity is believed to reduce breast cancer risk;
      however, its effect on breast density is not well understood. We studied the
      association between recreational physical activity and mammographic
      characteristics of the breast among a population of premenopausal and
      postmenopausal women enrolled as controls (n = 728) in a case-control study of
      mammographic breast density and breast cancer. Women were enrolled shortly after
      obtaining their regular screening mammograms, and participants reported their
      current and lifetime recreational physical activity history using a self
      administered, reliable questionnaire at study enrollment. Linear regression was
      used to determine associations between physical activity variables and the dense
      breast area, non-dense area, total breast area, and percent density. Age-adjusted
      analyses revealed significant inverse associations between physical activity
      variables and the non-dense area and total area and positive associations with
      percent breast density. These associations were attenuated and nonsignificant
      after adjustment for body mass index (BMI). Adjustment for additional factors did
      not substantially change the results. Physical activity was not associated with
      the dense breast area before or after adjustment for BMI. Self-reported
      recreational physical activity was not significantly associated with the
      mammographic characteristics of the breast after adjustment for BMI in this
      population. These results suggest that the mechanism by which physical activity
      reduces breast cancer risk may not involve breast density.

PMID- 17507620
TI  - Polymorphisms in the CYP19A1 (aromatase) gene and endometrial cancer risk in
      Chinese women.
AB  - Aromatase, encoded by the CYP19A1 gene, is a key enzyme in estradiol
      biosynthesis, which catalyzes the conversion of androstenedione and testosterone
      to estrone and estradiol, respectively. Given the critical role of estrogen in
      the development of endometrial cancer risk, we evaluated genetic polymorphisms of
      the CYP19A1 gene, including rs1065779, rs700519, rs28566535, rs752760, and
      rs1870050, in association with endometrial cancer in a population-based case
      control study conducted in Shanghai, China. Genotypes of 1,040 incident
      endometrial cancer cases and 1,031 frequency-matched controls were included in
      the study. We applied a logistic regression model to derive adjusted odds ratios
      (OR) and their 95% confidence intervals (95% CI). Six common haplotypes with a
      frequency >or=5% were estimated; the highest frequency haplotype was GCACA (27.8%
      in cases and 26.2% in controls). We observed an inverse association between
      CYP19A1 haplotype TCATC and endometrial cancer in our population (OR, 0.76; 95%
      CI, 0.62-0.92). An inverse association was found between endometrial cancer and
      single nucleotide polymorphism rs1870050 in the promoter region with ORs of 0.81
      (95% CI, 0.68-0.97) and 0.58 (95% CI, 0.42-0.80) for the AC and CC genotypes,
      respectively. We observed a multiplicative interaction between single nucleotide
      polymorphism rs700519 and body mass index among postmenopausal women (P = 0.01),
      with stronger associations between rs700519 genotypes and endometrial cancer risk
      among heavier (body mass index, >or=25) postmenopausal women. In summary, our
      data show that polymorphisms in the CYP19A1 gene may contribute to endometrial
      carcinogenesis.

PMID- 17507621
TI  - The reliability of nipple aspirate and ductal lavage in women at increased risk
      for breast cancer--a potential tool for breast cancer risk assessment and
      biomarker evaluation.
AB  - PURPOSE: Ductal lavage, a technique used to sample epithelial cells from breast
      ducts, has potential use in risk assessment and biomarker evaluation among women
      at increased risk for breast cancer. However, little is known about the
      reliability of the procedure. METHODS: We evaluated the reliability of nipple
      aspirate (NAF) and ductal lavage at two time points 6 months apart in women at
      increased risk for breast cancer. Eligible women had a 5-year Gail risk >or=1.66%
      or lifetime risk of >20%, and/or a family history or personal history of breast
      cancer. All ducts that produced NAF were cannulated. The kappa statistic was used
      to evaluate reliability of NAF production, cellular yield, and cytologic
      diagnosis. RESULTS: Sixty-nine women (mean age, 47 years) were enrolled over 35
      months. Forty-seven returned for a second visit. At baseline, 65% of
      premenopausal and 41% of postmenopausal women produced NAF (P = 0.05), of which
      72% underwent successful lavage of at least one duct. Samples of inadequate
      cellular material for diagnosis were significantly more likely in postmenopausal
      women than in premenopausal women (P = 0.04). Of the women who returned for a
      second visit, 18 of 24 who produced NAF had at least one duct successfully
      cannulated. Twenty-four ducts in 14 women were lavaged twice. Among these ducts,
      cellular yield for the two time points was inconsistent (kappa = 0.33 +/- 0.13),
      and only fair cytologic agreement was observed (kappa = 0.32 +/- 0.15). Ductal
      lavage was associated with moderate discomfort. CONCLUSION: Currently, the use of
      ductal lavage is limited by technical challenges in duct cannulation,
      inconsistent NAF production, a high rate of inadequate cellular material for
      diagnosis, fair cytologic reproducibility, and low participant return rates.

PMID- 17507622
TI  - Lactase persistence, dietary intake of milk, and the risk for prostate cancer in
      Sweden and Finland.
AB  - Prostate carcinoma is the most common cancer in men. Its primary pathogenesis is
      mostly unknown. Dairy products containing lactose have been suggested to be risk
      factors for prostate cancer. Digestion of lactose is dependent on lactase
      activity in the intestinal wall. A single nucleotide polymorphism C to T residing
      13,910 bp upstream of the lactase gene has been shown to associate with the
      developmental down-regulation of lactase activity underlying
      persistence/nonpersistence trait. To find out whether lactase persistence is
      related to the risk for prostate cancer, we genotyped 1,229 Finnish and 2,924
      Swedish patients and their 473 Finnish and 1,842 Swedish controls using solid
      phase minisequencing. To explore if dairy products have an association with
      prostate cancer, we analyzed the milk consumption in the Swedish study consisting
      of 1,499 prostate cancer patients and 1,130 controls (Cancer Prostate in Sweden I
      study) using a questionnaire. Only the consumption of low-fat milk was found to
      be associated with increased risk of prostate cancer [odds ratio (OR), 1.73; 95%
      confidence interval (95% CI), 1.16-2.39]. A statistically significantly higher (P
      < 0.01) lactose intake was observed among subjects with high lactase activity
      (C/T and T/T genotypes) compared with those with low lactase activity (C/C
      genotype). Lactase persistence did not associate with increased risk for prostate
      carcinoma in the Finnish (OR, 1.11; 95% CI, 0.83-1.47; P = 0.488) or in the
      Swedish populations (OR, 1.16; 95% CI, 0.91-1.46; P = 0.23). In conclusion,
      lactase persistence/nonpersistence contains no risk for prostate cancer. Analysis
      of different milk products showed some evidence for low-fat milk as a potential
      risk factor for prostate cancer.

PMID- 17507623
TI  - Serum lycopene, other carotenoids, and prostate cancer risk: a nested case
      control study in the prostate, lung, colorectal, and ovarian cancer screening
      trial.
AB  - BACKGROUND: Reports from several studies have suggested that carotenoids, and in
      particular lycopene, could be prostate cancer-preventive agents. This has
      stimulated extensive laboratory and clinical research, as well as much commercial
      and public enthusiasm. However, the epidemiologic evidence remains inconclusive.
      MATERIALS AND METHODS: We investigated the association between prediagnostic
      serum carotenoids (lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin,
      lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung,
      Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to
      examine methods of early detection and risk factors for cancer. The study
      included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study
      entry, including 270 aggressive cases, with regional or distant stage (n = 90) or
      Gleason score >or=7 (n = 235), and 844 randomly selected, matched controls. As
      study participants were selected from those who were assigned to annual
      standardized screening for prostate cancer, results are unlikely to be biased by
      differential screening, a circumstance that is difficult to attain under non
      trial conditions. RESULTS: No association was observed between serum lycopene and
      total prostate cancer [odds ratios (OR), 1.14; 95% confidence intervals (95% CI),
      0.82-1.58 for highest versus lowest quintile; P for trend, 0.28] or aggressive
      prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile;
      P for trend, 0.433). beta-Carotene was associated with an increased risk of
      aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72 for highest versus lowest
      quintile; P for trend, 0.13); in particular, regional or distant stage disease
      (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile; P for trend,
      0.02); other carotenoids were not associated with risk. CONCLUSION: In this large
      prospective study, high serum beta-carotene concentrations were associated with
      increased risk for aggressive, clinically relevant prostate cancer. Lycopene and
      other carotenoids were unrelated to prostate cancer. Consistent with other recent
      publications, these results suggest that lycopene or tomato-based regimens will
      not be effective for prostate cancer prevention.

PMID- 17507624
TI  - Evaluation of genetic variations in the androgen and estrogen metabolic pathways
      as risk factors for sporadic and familial prostate cancer.
AB  - Previous studies suggest that enzymes involved in the androgen metabolic pathway
      are susceptibility factors for prostate cancer. Estrogen metabolites functioning
      as genotoxins have also been proposed as risk factors. In this study, we
      systematically tested the hypothesis that common genetic variations for those
      enzymes involved in the androgen and estrogen metabolic pathways increase risk
      for sporadic and familial prostate cancer. From these two pathways, 46
      polymorphisms (34 single nucleotide polymorphisms, 10 short tandem repeat
      polymorphisms, and 2 null alleles) in 25 genes were tested for possible
      associations. Those genes tested included PRL, LHB, CYP11A1, HSD3B1, HSD3B2,
      HSD17B2, CYP17, SRD5A2, AKR1C3, UGT2B15, AR, SHBG, and KLK3 from the androgen
      pathway and CYP19, HSD17B1, CYP1A1, CYP1A2, CYP1B1, COMT, GSTP1, GSTT1, GSTM1,
      NQO1, ESR1, and ESR2 from the estrogen pathway. A case-control study design was
      used with two sets of cases: familial cases with a strong prostate cancer family
      history (n = 438 from 178 families) and sporadic cases with a negative prostate
      cancer family history (n = 499). The controls (n = 493) were derived from a
      population-based collection. Our results provide suggestive findings for an
      association with either familial or sporadic prostate cancer with polymorphisms
      in four genes: AKR1C3, HSD17B1, NQO1, and GSTT1. Additional suggestive findings
      for an association with clinical variables (disease stage, grade, and/or node
      status) were observed for single nucleotide polymorphisms in eight genes: HSD3B2,
      SRD5A2, SHBG, ESR1, CYP1A1, CYP1B1, GSTT1, and NQO1. However, none of the
      findings were statistically significant after appropriate corrections for
      multiple comparisons. Given that the point estimates for the odds ratio for each
      of these polymorphisms are <2.0, much larger sample sizes will be required for
      confirmation.

PMID- 17507625
TI  - Prognostic effect of DNA aneuploidy from bladder washings in superficial bladder
      cancer.
AB  - BACKGROUND: Superficial (papillary) bladder cancer is associated with progression
      and death from muscle-invasive bladder cancer, but no reliable predictors of the
      outcomes have been identified. METHODS: We analyzed the long-term prognostic
      effect of DNA flow cytometry in bladder washings from 93 subjects with previously
      resected T(a) and T(1) bladder tumors who participated in a chemoprevention trial
      of the synthetic retinoid fenretinide. Kaplan-Meier analysis and Cox regression
      were used to determine the prognostic effect of DNA aneuploidy on cancer
      progression and mortality in conjunction with conventional clinical factors after
      a median of 11.5 years (interquartile range, 9.5-11.7 years). RESULTS: Overall,
      58 of 93 (62%) specimens were DNA aneuploid at baseline. Progression-free
      survival was significantly shorter in subjects with stage T(1) [hazard ratio
      (HR), 31.6; 95% confidence interval (95% CI), 2.6-386.1; P < 0.001] and in
      subjects with baseline DNA aneuploid washing (HR, 10.5; 95% CI, 1.1-126.1; P =
      0.03). The risk of death was also greater for stage T(1) tumors (HR, 2.6; 95% CI,
      1.04-6.7; P = 0.04). DNA aneuploidy was a significant prognostic factor also for
      overall survival (HR, 2.8; 95% CI, 1.0-9.0; P = 0.05). Fenretinide treatment had
      no significant effect on cancer progression and death. CONCLUSIONS: DNA
      aneuploidy in washings from endoscopically normal bladder is a significant
      predictor of progression and death in addition to tumor stage. This biomarker may
      help to identify and monitor a high-risk group who may benefit from a
      chemoprevention intervention.

PMID- 17507626
TI  - Associations between exercise and quality of life in bladder cancer survivors: a
      population-based study.
AB  - BACKGROUND: Exercise has been shown to improve quality of life (QoL) in some
      cancer survivor groups, but it is unknown if the unique QoL issues faced by
      bladder cancer survivors are also amenable to an exercise intervention. This
      study provides the first data examining the association between exercise and QoL
      in bladder cancer survivors. METHODS: Bladder cancer survivors identified through
      a provincial cancer registry were mailed a survey that included the Godin Leisure
      Time Exercise Questionnaire, the Functional Assessment of Cancer Therapy-Bladder
      (FACT-Bl) scale, and the Fatigue Symptom Inventory. RESULTS: Of the 525 bladder
      cancer survivors (51% response rate) that completed the survey, 22.3% were
      meeting public health exercise guidelines in the past month, 16.0% were
      insufficiently active (i.e., some exercise but less than the guidelines), and
      61.7% were completely sedentary. ANOVA indicated a general linear association
      between meeting guidelines and QoL, with those meeting guidelines reporting more
      favorable scores than completely sedentary survivors on the FACT-Bl (mean
      difference, 7.6; 95% confidence interval, 3.6-11.7; P < 0.001), the FACT (P =
      0.001), the trial outcome index (P < 0.001), functional well-being (P < 0.001),
      additional concerns (P = 0.001), sexual functioning (P < 0.001), erectile
      function (P < 0.001), body image (P < 0.001), and various fatigue indicators (P <
      0.05). Adjusting for key medical and demographic factors slightly attenuated the
      magnitude of the associations but did not alter the substantive conclusions.
      CONCLUSIONS: Exercise is positively associated with QoL in bladder cancer
      survivors, although few are meeting public health exercise guidelines. Studies
      testing the causal effects of exercise on QoL issues unique to this population
      are warranted.

PMID- 17507627
TI  - Number of nevi and early-life ambient UV exposure are associated with BRAF-mutant
      melanoma.
AB  - Malignant melanomas often contain BRAF or NRAS mutations, but the relationship of
      these mutations to ambient UV exposure in combination with phenotypic
      characteristics is unknown. In a population-based case series from North
      Carolina, 214 first primary invasive melanoma patients in the year 2000 were
      interviewed regarding their risk factors. Ambient solar UV exposures were
      estimated using residential histories and a satellite-based model. Cases were
      grouped on the basis of BRAF and NRAS somatic mutations, determined using single
      strand conformation polymorphism analysis and radiolabeled DNA sequencing, and
      the risk profiles of these groups were compared. Mutually exclusive BRAF-mutant
      and NRAS-mutant cases occurred at frequencies of 43.0% and 13.6% with mean ages
      at diagnosis of 47.3 and 62.1 years, respectively. Tumors from patients with >14
      back nevi were more likely to harbor either a BRAF mutation [age-adjusted odds
      ratio (OR), 3.2; 95% confidence interval (95% CI), 1.4-7.0] or an NRAS mutation
      (age-adjusted OR, 1.7; 95% CI, 0.6-4.8) compared with patients with 0 to 4 back
      nevi. However, BRAF-mutant and NRAS-mutant tumors were distinctive in that BRAF
      mutant tumors were characteristic of patients with high early-life ambient UV
      exposure (adjusted OR, 2.6; 95% CI, 1.2-5.3). When ambient UV irradiance was
      analyzed by decadal age, high exposure at ages 0 to 20 years was associated with
      BRAF-mutant cases, whereas high exposure at ages 50 and 60 years was
      characteristic of NRAS-mutant cases. Our results suggest that although nevus
      propensity is important for the occurrence of both BRAF and NRAS-mutant
      melanomas, ambient UV irradiance influences risk differently based on the age of
      exposure. The association of BRAF mutations with early-life UV exposure provides
      evidence in support of childhood sun protection for melanoma prevention.

PMID- 17507628
TI  - Fatalistic beliefs about cancer prevention and three prevention behaviors.
AB  - BACKGROUND: A substantial proportion of US adults hold fatalistic beliefs about
      cancer prevention. Although evidence suggests that fatalistic beliefs discourage
      people from engaging in screening behaviors that can reduce their cancer risk,
      far less is known about associations between cancer fatalism and other prevention
      behaviors. We examined sociodemographic correlates of these beliefs and their
      associations with regular exercise, smoking, and fruit and vegetable consumption
      with a national sample of American adults. METHODS: Data were analyzed from the
      first wave of the Health Information National Trends Survey (HINTS 2003). HINTS
      used random-digit dialing to complete phone interviews with adult Americans (N =
      6,369). RESULTS: Nearly half of respondents (47.1%) agreed that "It seems like
      almost everything causes cancer," 27.0% agreed that "There's not much people can
      do to lower their chances of getting cancer," and 71.5% agreed that "There are so
      many recommendations about preventing cancer, it's hard to know which ones to
      follow." These beliefs were stronger in subjects who were less educated but
      generally weaker among both African Americans and Hispanics relative to Whites.
      Fatalistic beliefs about cancer prevention were negatively associated with
      exercising weekly, not smoking, and eating five or more fruits and vegetables
      daily in multivariate analysis controlling for sociodemographic characteristics.
      CONCLUSIONS: Americans who hold fatalistic beliefs about cancer prevention may be
      at greater risk of cancer because they are less likely to engage in various
      prevention behaviors. Results have notable implications for future cancer
      communication and education efforts.

PMID- 17507629
TI  - Reproducibility of serum sex steroid assays in men by RIA and mass spectrometry.
AB  - There is an increasing trend to apply gas chromatography combined with mass
      spectrometry (GC-MS) or liquid chromatography tandem mass spectrometry (LC-MS/MS)
      assay methods to large-scale epidemiologic studies for the measurement of serum
      sex steroids. These methods are generally considered the gold standard for sex
      steroid measurements because of their accuracy, sensitivity, turnaround time, and
      ability to assess a more complete panel of steroid metabolites in the same run.
      In this report, we evaluated the precision, including within-batch (intra) and
      between-batch (inter) reproducibility, of steroid hormone measurements determined
      by GC-MS and LC-MS/MS assays and RIA and compared measurements among these
      methods. Specifically, 282 overnight fasting serum samples from 20 male
      volunteers were analyzed for 12 steroid metabolites by GC-MS or LC-MS/MS in one
      lab over a 4-month period. Six of the analytes were also measured by RIA in
      another lab. Unconjugated hormones, including testosterone, dihydrotestosterone,
      dehydroepiandrosterone, androstenedione, androst-5-ene-3beta,17beta-diol,
      estrone, and estradiol, were measured by GC-MS, whereas conjugated hormones,
      including DHEA sulfate, androsterone glucuronide, 5alpha-androstane-3alpha,17beta
      diol 3-glucuronide, 5alpha-androstane-3alpha,17beta-diol 17-glucuronide, and
      estrone sulfate, were measured by LC-MS/MS. A subset of these hormones, including
      testosterone, dihydrotestosterone, androstenedione, 5alpha-androstane
      3alpha,17beta-diol 17-glucuronide, estrone, and estradiol, were also measured by
      RIA following extraction and chromatography. We used the coefficient of variation
      (CV) and the intraclass correlation coefficient (ICC) to assess within- and
      between-batch assay variations. For the 12 analytes measured by GC-MS or LC
      MS/MS, CVs and ICCs for within- and between-batch measurements were similar, with
      CVs ranging from 6.1% to 21.4% and ICCs ranging from 87.6% to 99.2%. The six
      analytes measured by RIA had good CVs and ICCs, with CVs <10% and ICCs >70%
      (range, 71.7-99.7%). For the six metabolites that were measured by both methods,
      the CVs were similar, whereas the ICCs were generally higher with the GC-MS
      method. The absolute values for each analyte measured by RIA and GC-MS differed,
      with RIAs usually yielding markedly higher levels than GC-MS, although the
      Pearson and Spearman correlation coefficients for these six analytes were near
      one and all were significant (P < 0.001). Our results show that RIA, GC-MS, and
      LC-MS/MS assays for androgens and estrogens in the two labs included in the study
      have good reproducibility, as measured by small CVs (<15%) and high ICCs (>80%),
      with the exception of estradiol (71.7%) when measured by RIA. Despite substantial
      differences in absolute measurements of sex steroid hormones by RIA and MS
      methods, correlations between the two assays for the six sex steroids measured in
      the two labs were high (>0.9). However, it is important for future large
      epidemiologic studies to incorporate MS with high reproducibility and specificity
      to measure a more complete profile of androgen and estrogen metabolites to
      clarify the role of sex steroids in prostate cancer.

PMID- 17507630
TI  - Phytoestrogen exposure is associated with circulating sex hormone levels in
      postmenopausal women and interact with ESR1 and NR1I2 gene variants.
AB  - In this large cross-sectional study, we investigated the relationship between
      phytoestrogen exposure and circulating sex hormones and sex hormone-binding
      globulin (SHBG) levels in 1988 healthy postmenopausal women and their
      interactions with polymorphisms in genes involved in estrogen signaling. Plasma
      estradiol, testosterone, androstenedione, estrone, and SHBG were measured.
      Urinary levels of five isoflavones (daidzein, genistein, glycitein, O
      desmethylangolensin, and equol) and two lignans (enterodiol and enterolactone)
      were measured and used as biomarkers for dietary intakes. Eighteen polymorphisms
      in ESR1, ESR2, and NR1I2 genes were genotyped. Results showed that lignans were
      positively associated with plasma SHBG levels (eta(p)(2) = 1.2%; P < 0.001) and
      negatively associated with plasma testosterone (eta(p)(2) = 0.2%; P = 0.042).
      Equol was negatively associated with plasma estradiol levels (eta(p)(2) = 0.3%; P
      = 0.028), whereas O-desmethylangolensin was positively associated with plasma
      estradiol level (eta(p)(2) = 0.3%; P = 0.010). There were significant
      phytoestrogen interactions with polymorphisms in ESR1 and NR1I2 genes in
      affecting estrone levels. We conclude that phytoestrogens modulate sex hormone
      and SHBG levels in postmenopausal women and interact with gene variants involved
      in estrogen signaling. Such phytoestrogen-gene interactions may explain the
      conflicting literature on the hormonal effects of phytoestrogens.

PMID- 17507631
TI  - Serum levels of insulin-like growth factor-I and insulin-like growth factor-I
      binding protein-3: quality control for studies of stored serum.
AB  - The insulin-like growth factor (IGF) axis, particularly IGF-I and IGF binding
      protein-3 (IGFBP-3), has been the subject of much attention because of its role
      in juvenile growth and their association with cancers at several sites. However,
      epidemiologic studies of IGF-I and IGFBP-3 have had mixed results and several
      authors have speculated that quality control (QC), sample storage history, and
      other methodologic concerns could play a role in this heterogeneity. This article
      documents the results of storage history and QC efforts for a study of IGF-I and
      IGFBP-3 in 6,226 serum samples from the National Health and Nutrition Examination
      Survey III (NHANES III). The study was carried out on site at Diagnostic Systems
      Laboratories in Webster, Texas, using the IGF-I ELISA (DSL 10-5600) and the IGFBP
      3 immunoradiometric assay (DSL 6600). A run-in study of assay performance
      suggested that plates, days, and weeks significantly affected the variance of
      both assays. Analysis of samples with different storage histories also indicated
      strong effects of storage history. Serum samples disbursed to laboratories for
      measurement of diverse analytes and then returned for storage showed reductions
      in serum IGF-I level averaging 43% and reductions in IGFBP-3 of 25% compared with
      samples shipped immediately to the repository for long-term storage at -80
      degrees C. Therefore, the main study was carried out using samples that had been
      shipped directly to the National Center for Health Statistics/NHANES collection
      center for storage. Laboratory analyses of NHANES III and QC samples were carried
      out over approximately 10 months. QC was monitored through repeated testing of
      blood samples from six individuals, with two individuals tested twice on each
      plate. Assay performance was stable over the entire study and coefficients of
      variation averaged 2% to 3% within plates and approximately 14% for IGF-I and
      approximately 11.5% for IGFBP-3 over the entire study. Coefficients of variation
      varied significantly among individual QC subjects, ranging from 12.3% to 17.6%
      for IGF-I and 8.9% to 12.8% for IGFBP-3. Based on Levy-Jennings plots,
      approximately 5% of the plates used for IGF-I in the main study were out of
      compliance. Finally, location on a plate had small but significant effects on IGF
      I level. Together, these results highlight the need for care in large studies of
      putative biomarkers for cancer risk and illustrate some probable sources of
      heterogeneity in past epidemiologic studies of the IGF axis and cancer.

PMID- 17507632
TI  - Successful genome-wide scan in paired blood and buccal samples.
AB  - Interest in genome-wide association studies to identify susceptibility alleles
      for cancer is growing, and several are currently planned or under way. Although
      the feasibility of collecting buccal cell samples as an alternative to venous
      blood samples as a source of genomic DNA has been shown, the validity of using
      DNA from buccal cells for genome-wide scans has not been assessed. We used 46
      paired buffy coat and buccal cell samples to test the feasibility of using DNA
      from buccal cells for genotyping with the HumanHap300 Bead Chip (v.1.0.0) on the
      Illumina Infinium II platform. Genotyping was successful in every sample,
      regardless of DNA yield or sample type. Of the 317,502 genotypes attempted,
      315,314 (99.3%) were successfully called. Completion rates were similar for buffy
      coat and buccal cell samples (99.63% and 99.44%, respectively; P = 0.15).
      Completion rates <99% were observed in only four samples and did not differ by
      specimen type. The paired samples showed exceptionally high concordance (99.96%).
      These results show that buccal cell samples collected and processed under optimal
      conditions can be used for genome-wide association studies with results
      comparable to those obtained from DNA extracted from buffy coat.

PMID- 17507633
TI  - Cardiovascular risk profile of patients with HER2/neu-positive breast cancer
      treated with anthracycline-taxane-containing adjuvant chemotherapy and/or
      trastuzumab.
AB  - PURPOSE: To evaluate the cardiovascular risk profile of a subset of patients with
      early-stage breast cancer treated with adjuvant taxane-anthracycline-containing
      chemotherapy and/or trastuzumab (Herceptin). EXPERIMENTAL DESIGN: Twenty-six
      patients with breast cancer (mean, 20 months postchemotherapy) and 10 healthy age
      matched women were studied. We measured 14 metabolic and vascular established
      cardiovascular disease (CVD) risk factors, body mass index, cardiorespiratory
      fitness, and left ventricular systolic function. All assessments were done within
      a 14-day period. RESULTS: Cardiac abnormalities were suggested by left
      ventricular ejection fraction (LVEF) <50% in 8% of patients, LVEF remained >10%
      below pretreatment values in 38%, whereas 50% presented with resting sinus
      tachycardia. Brain natriuretic peptide was significantly elevated in 40% of
      patients and was correlated with LVEF (r = -0.72, P =or< 0.001). For the majority
      of CVD risk factors, similar proportions of patients and controls (35-60%) were
      classified as "undesirable." A significantly higher proportion of patients were
      classified with low cardiorespiratory fitness (46% versus 0%, P < 0.01), being
      overweight/obese (72% versus 50%, P < 0.05), and having resting sinus tachycardia
      (50% versus 0%, P < 0.01) compared with controls. Cardiorespiratory fitness and
      body mass index were correlated with CVD risk factors (r = -0.64 to 0.63, P <
      0.05; r = -0.63 to 0.67, P < 0.05, respectively). Exploratory analyses revealed
      several differences between CVD risk factors based on chemotherapy regimen.
      CONCLUSION: Breast cancer survivors treated with adjuvant chemotherapy are at a
      higher risk of developing late-occurring CVD than age-matched controls due to
      direct and indirect treatment-related toxicity.

PMID- 17507634
TI  - Atypia in random periareolar fine-needle aspiration affects the decision of women
      at high risk to take tamoxifen for breast cancer chemoprevention.
AB  - Random periareolar fine-needle aspiration (RPFNA) is a research procedure
      designed to (a) evaluate short-term breast cancer risk in women at high risk for
      developing breast cancer, and (b) track response to chemoprevention. Of import,
      cellular atypia in breast RPFNA is prospectively associated with a 5.6-fold
      increase in breast cancer risk in women at high risk. Among 99 women attending a
      clinic for high-risk breast cancer, we explored the effects of RPFNA cytology
      results on decision making pertaining to the use of tamoxifen for breast cancer
      chemoprevention. No patient with nonproliferative or hyperplastic cytology
      subsequently elected to take tamoxifen. Only 7% of subjects with borderline
      atypia elected to take tamoxifen. In contrast, 50% with atypia elected to take
      tamoxifen. These results suggest that the provision of a biomarker of short-term
      risk can affect the motivation to take tamoxifen for chemoprevention. This
      conclusion is informative given that tamoxifen, due to its side effects, is often
      underused by women at high risk of developing breast cancer. Further research is
      needed to determine the mechanisms through which RPFNA results affect the
      decision to use tamoxifen, or any other breast cancer chemopreventive agent.

PMID- 17507635
TI  - Hair relaxers not associated with breast cancer risk: evidence from the black
      women's health study.
AB  - Hair relaxers (straighteners) have been used by millions of African American
      women, often for many years. Relaxer ingredients can enter the body through scalp
      lesions and burns. Because manufacturers are not required to list all
      ingredients, these products may contain unknown harmful substances. We assessed
      hair relaxer use in relation to breast cancer incidence in the Black Women's
      Health Study, a nationwide follow-up study of African American women. Information
      on hair relaxer use was collected in 1997; 48,167 women were followed
      subsequently through 2003 for incident breast cancer. Incidence rate ratios of
      breast cancer were estimated with Cox regression. During 266,298 person-years of
      follow-up, 574 incident cases of breast cancer were ascertained. There were no
      increases in breast cancer risk associated with any categories of duration of
      hair relaxer use, frequency of use, age at first use, number of burns experienced
      during use, or type of relaxer used. The incidence rate ratio for use at least
      seven times a year for 20 or more years relative to use for less than a year was
      0.98 (95% confidence interval, 0.78-1.39). These results suggest that hair
      relaxer use does not increase the incidence of breast cancer in African American
      women.

PMID- 17507636
TI  - Concordance of pharmacogenetic polymorphisms in tumor and germ line DNA in adult
      patients with acute myeloid leukemia.
AB  - Archived tumor tissue is a useful resource for retrospective studies addressing
      relationships between genetic polymorphisms and treatment outcomes. However,
      genotypes determined in tumor and somatic tissues may differ due to cytogenetic
      and molecular changes associated with malignant transformation and progression.
      Discordance between germ line and tumor genotypes may be particularly relevant in
      leukemia because cytogenetic abnormalities are frequent. We compared genotypes
      determined in DNA extracted from paired pretreatment bone marrow and buccal
      samples from 80 adult patients with acute myeloid leukemia (AML). Paired AML and
      buccal DNA samples were genotyped for polymorphisms (21 single nucleotide
      polymorphisms and 2 gene deletions) on genes encoding proteins involved in drug
      metabolism (CYP3A4, CYP2C8, CDA, and GSTP1), oxidative stress mechanisms (CAT,
      MnSOD, GSTT1, GSTM1, GSTA1, and GPX1), drug transport (MDR1, MRP1, and BCRP), and
      DNA repair (MGMT, XPD, and XRCC1). Genotypes were determined by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry, except GSTM1 and
      GSTT1, for which deletion genotypes were determined using multiplex PCR.
      Concordance of genotypes was tested by kappa statistics. kappa statistics for
      paired AML and buccal DNA samples ranged between 0.94 and 1.00, indicating
      excellent agreement. The GSTT1 and GSTM1 genotypes were in perfect concordance
      for the paired samples. Agreement was also excellent for genes at AML chromosome
      deletion and translocation breakpoints, including MDR1 at 7q21.1 and MRP1 at
      16p13.1. Based on these data, genotypes derived from archived AML bone marrow
      samples were not likely to differ from those from genomic DNA, and archived bone
      marrow samples may be useful for the conduct of retrospective pharmacogenetic
      studies.

PMID- 17507637
TI  - A novel cyclic adenosine monophosphate responsive luciferase reporter
      incorporating a nonpalindromic cyclic adenosine monophosphate response element
      provides optimal performance for use in G protein coupled receptor drug discovery
      efforts.
AB  - The authors report the characterization of a novel cyclic adenosine monophosphate
      (cAMP)-responsive luciferase (Luc) reporter that exhibits optimal performance in
      high-throughput screens of agonist binding at G protein-coupled receptors
      (GPCRs). This reporter (RIP1-CRE-Luc) incorporates a nonpalindromic cAMP response
      element (CRE) originally identified within the 5' promoter of the rat insulin 1
      gene (RIP1). When multimerized and fused to the coding sequence of firefly
      luciferase, the CRE of RIP1 allows for the efficient activation of luciferase
      expression by cAMP-elevating agents or by cAMP itself. Of primary importance is
      the demonstration that RIP1-CRE-Luc does not exhibit the relatively high levels
      of basal luciferase activity inherent to reporters incorporating the palindromic
      CRE first identified in the somatostatin gene promoter. Furthermore, studies of
      HEK cells expressing class II GPCRs for the cAMP-elevating hormones GLP-1, GIP,
      and glucagon demonstrate that RIP1-CRE-Luc affords a much wider dynamic range of
      activation upon exposure to agonist. Such properties of RIP1-CRE-Luc indicate its
      usefulness as a new and powerful tool for the identification of small-molecule
      compounds with receptor-stimulating actions or for the identification of
      constitutively active orphan receptors with cAMP-signaling properties.

PMID- 17507638
TI  - A microtiter assay for quantifying protein-protein interactions associated with
      cell-cell adhesion.
AB  - Cell-cell adhesions are a hallmark of epithelial tissues, and the disruption of
      these contacts plays a critical role in both the early and late stages of
      oncogenesis. The interaction between the transmembrane protein E-cadherin and the
      intracellular protein beta-catenin plays a crucial role in the formation and
      maintenance of epithelial cell-cell contacts and is known to be downregulated in
      many cancers. The authors have developed a protein complex enzyme-linked
      immunosorbent assay (ELISA) that can quantify the amount of beta-catenin bound to
      E-cadherin in unpurified whole-cell lysates with a Z' factor of 0.74. The
      quantitative nature of the E-cadherin:beta-catenin ELISA represents a dramatic
      improvement over the low-throughput assays currently used to characterize
      endogenous E-cadherin:beta-catenin complexes. In addition, the protein complex
      ELISA format is compatible with standard sandwich ELISAs for parallel
      measurements of total levels of endogenous E-cadherin and beta-catenin. In 2 case
      studies closely related to cancer cell biology, the authors use the protein
      complex ELISA and traditional sandwich ELISAs to provide a detailed, quantitative
      picture of the molecular changes occurring within adherens junctions in vivo.
      Because the E-cadherin: beta-catenin protein complex plays a crucial role in
      oncogenesis, this protein complex ELISA may prove to be a valuable quantitative
      prognostic marker of tumor progression.

PMID- 17507639
TI  - High-content classification of nucleocytoplasmic import or export inhibitors.
AB  - Transcription factors of the nuclear factor kappa B family are the paradigm for
      signaling dependent nuclear translocation and are ideally suited to analysis
      through image-based chemical genetic screening. The authors describe combining
      high-content image analysis with a compound screen to identify compounds
      affecting either nuclear import or export. Validation in silico and in vitro
      determined an EC(50) for the nuclear export blocker leptomycin B of 2.4 ng/mL
      (4.4 nM). The method demonstrated high selectivity (Z' >0.95), speed, and
      robustness in a screen of a compound collection. It identified the IkappaB
      protein kinase inhibitor BAY 11 7082 as an import inhibitor, the p38 mitogen
      activated protein (MAP) kinase inhibitor PD98509 as an import enhancer, and
      phorbol ester as an export inhibitor. The results establish a robust method for
      identifying compounds regulating nucleocytoplasmic import or export and also
      implicate MAP kinases in nuclear import of nuclear factor kappa B.

PMID- 17507640
TI  - Screening library evolution through automation of solution preparation.
AB  - The quality of the compound library is a critical success factor in every high
      throughput screening campaign. Screening solutions have to be prepared with a
      high level of process control to ensure the correct identity and initial
      concentration of each compound. However, even under optimized storage conditions,
      a certain level of degradation in solution cannot be avoided. Therefore, regular
      quality control and eventual removal of solutions from the screening deck is
      necessary. Because solution preparation, especially the weighing of compounds, is
      a tedious and often manual task, a regular resolubilization of compounds is
      difficult to achieve. By complete automation of the solution preparation, the
      authors have laid the foundation for a life cycle management of screening
      solutions. They demonstrate how a combination of quality and process control
      leads to a continuous improvement of the screening library. In presenting an
      automation concept, they show how a series of innovative process optimizations
      led to a high-performance system that achieves full industrialization of solution
      preparation.

PMID- 17507641
TI  - Gait training induced change in corticomotor excitability in patients with
      chronic stroke.
AB  - BACKGROUND: Numerous studies have reported the effects of gait training on motor
      performance after stroke. However, there is limited information on treatment
      induced changes in corticomotor excitability. OBJECTIVES: The purpose of the
      study was to investigate the effects of additional gait training on motor
      performance and corticomotor excitability and to demonstrate the relationship
      between motor improvement and corticomotor excitability change in patients with
      chronic stroke. METHODS: Fourteen patients were randomly assigned to the
      experimental or control group. Participants in both groups participated in
      general physical therapy. Those in the experimental group received additional
      body weight- supported treadmill training for 4 weeks. All participants received
      baseline and posttreatment assessments. The outcome measures included assessment
      of the Berg Balance Scale (BBS) and gait parameters. Focal transcranial magnetic
      stimulation was used to measure the motor threshold, map size, and location of
      the amplitude-weighted center of gravity of the motor map for the tibialis
      anterior (TA) and abductor hallucis (AH) muscles. RESULTS: After general physical
      therapy, we noted that the patients showed an improvement only in walking speed
      and cadence, and there were no significant changes in corticomotor excitability.
      After additional gait training, participants improved significantly on BBS score,
      walking speed, and step length. Moreover, the motor threshold for TA decreased
      significantly in the unaffected hemisphere. The map size for TA was increased in
      both hemispheres, whereas that for AH was increased only in the affected
      hemisphere. There were significant differences between the change scores of the
      groups in terms of walking speed, step length, and motor threshold for TA in the
      unaffected hemisphere and map size for AH in the affected hemisphere.
      Additionally, the changes in corticomotor excitability correlated with functional
      improvement. CONCLUSIONS: Additional gait training may improve balance and gait
      performance and may induce changes in corticomotor excitability.

PMID- 17507643
TI  - Sensorimotor cortical plasticity during recovery following spinal cord injury: a
      longitudinal fMRI study.
AB  - BACKGROUND: Although the consequences of spinal cord injury (SCI) within the
      spinal cord and peripheral nervous system have been studied extensively, the
      influence of SCI on supraspinal structures during recovery remains largely
      unexplored. OBJECTIVE: To assess temporal changes in cortical sensorimotor
      representations beginning in the subacute phase following SCI and determine if an
      association exists between the plastic changes within cortical sensorimotor areas
      and recovery of movement postinjury. METHODS: Functional magnetic resonance
      imaging (fMRI) was used to study 6 SCI patients for 1 year, beginning shortly
      postinjury, and 10 healthy control individuals. During fMRI, individuals
      performed a simple self-paced wrist extension motor task. Recovery of movement
      was assessed using the American Spinal Injury Association (ASIA) Standard
      Neurological Classification of SCI. RESULTS: In the subacute period post-SCI,
      during impaired movement, little task-related activation within the primary motor
      cortex (M1) was present, whereas activation in associated cortical sensorimotor
      areas was more extensive than in controls. During motor recovery, a progressive
      enlargement in the volume of movement-related M1 activation and decreased
      activation in associated cortical sensorimotor areas was seen. When movement was
      performed with little to no impairment, the overall pattern of cortical
      activation was similar to that observed in control individuals. CONCLUSIONS: This
      study provides the first report of the temporal progression of cortical
      sensorimotor representational plasticity during recovery following traumatic SCI
      in humans and suggests an association between movement-related fMRI activation
      and motor recovery postinjury. These findings have implications on current and
      future rehabilitative interventions for patients with SCI.

PMID- 17507642
TI  - Validity of the walking scale for spinal cord injury and other domains of
      function in a multicenter clinical trial.
AB  - OBJECTIVE: To demonstrate criterion (concurrent and predictive) and construct
      validity of the Walking Index for Spinal Cord Injury (WISCI) scale and other
      walking measures in the Spinal Cord Injury Locomotor Trial (SCILT). DESIGN:
      Prospective multicenter clinical trial of a walking intervention for patients
      with acute traumatic spinal cord injury (SCI). PARTICIPANTS/ METHODS: Body weight
      supported treadmill training was compared to overground mobility training in 146
      patients with incomplete SCI (C4 to L3) enrolled within 8 weeks of onset and
      treated for 12 weeks. Primary outcome measures were the Functional Independence
      Measure (FIM), 50-foot walking speed (50FW-S), and 6-minute walking distance (6MW
      D), tested 3, 6, and 12 months after entry. Secondary measures were the Lower
      Extremity Motor Score (LEMS), Berg Balance Scale (BBS), WISCI, and FIM locomotor
      score (LFIM), assessed at 6 centers by blinded observers. Data for the 2 arms
      were combined since no significant differences in outcomes had been found.
      RESULTS: Correlations with WISCI at 6 months were significant with BBS (r = .90),
      LEMS (r = .85), LFIM (r = .89), FIM (r = .77), 50FW-S (r = .85), and 6MW-D ( r =
      .79); similar correlations occurred at 3 and 12 months. Correlations of change
      scores from baseline WISCI were significant for change scores from baseline of
      LEMS/BBS/LFIM. Correlation of baseline LEMS and WISCI at 12 months were most
      significant (r = .73). The R(2) of baseline LEMS explained 57% of variability of
      WISCI levels at 3 months. CONCLUSION: Concurrent validity of the WISCI scale was
      supported by significant correlations with all measures at 3, 6, and 12 months.
      Correlation of change scores supports predictive validity. The LEMS at baseline
      was the best predictor of the WISCI score at 12 months and explained most of the
      variance, which supported both predictive and construct validity. The combination
      of the LEMS, BBS, WISCI, 50FW-S, and LFIM appears to encompass adequate
      descriptors for outcomes of walking trials for incomplete SCI.

PMID- 17507644
TI  - Relationship between interhemispheric inhibition and motor cortex excitability in
      subacute stroke patients.
AB  - BACKGROUND: Studies of stroke patients using functional imaging and transcranial
      magnetic stimulation (TMS) of the primary motor cortex (M1) demonstrated
      increased recruitment and abnormally decreased short interval cortical inhibition
      (SICI) of the M1 contralateral to the lesioned hemisphere (contralesional M1)
      within the first month after infarction of the M1 or its corticospinal
      projections. OBJECTIVE: The authors sought to identify mechanisms underlying
      decreased SICI of the contralesional M1. METHODS: In patients within 6 weeks of
      their first ever infarction of the M1 or its corticospinal projections, SICI in
      the M1 of the lesioned and nonlesioned hemisphere was studied using paired-pulse
      TMS. Interhemispheric inhibition (IHI) was measured by applying TMS to the M1 of
      the lesioned hemisphere and a second pulse to the homotopic M1 of the nonlesioned
      hemisphere and vice versa with the patient at rest. The results were compared to
      M1 stimulation of age-matched healthy controls. RESULTS: SICI was decreased in
      the M1 of lesioned and nonlesioned hemispheres regardless of cortical or
      subcortical infarct location. IHI was abnormally decreased from the M1 of the
      lesioned on nonlesioned hemisphere. In contrast, IHI was normal from the M1 of
      the nonlesioned on the lesioned hemisphere. Abnormal IHI and SICI were correlated
      in patients with cortical but not with subcortical lesions. CONCLUSIONS: In
      subacute stroke patients, abnormally decreased SICI of a contralesional M1 can
      only partially be explained by loss of IHI from the lesioned on nonlesioned
      hemisphere. As decreased SICI of the contralesional M1 did not result in
      excessive IHI from the nonlesioned on lesioned hemisphere with subsequent
      suppression of ipsilesional M1 excitability and all patients showed excellent
      recovery of motor function, decreased SICI of the contralesional M1 may represent
      an adaptive process supporting recovery.

PMID- 17507645
TI  - Wallerian degeneration of the corticofugal tracts in chronic stroke: a pilot
      study relating diffusion tensor imaging, transcranial magnetic stimulation, and
      hand function.
AB  - OBJECTIVE: This study tested the hypothesis that degeneration of the corticofugal
      tracts (CFTs) is related to poor functional outcome in the upper limb after
      stroke. METHODS: . The authors used diffusion tensor imaging to determine the
      degree of white matter integrity of the CFT (FA(AH/UH)) in chronic stroke
      patients and controls. The functional integrity of the corticospinal pathway was
      examined using transcranial magnetic stimulation. Recruitment curves and silent
      period duration were measured. The relationship between FA(AH/UH) and functional
      outcome of the upper limb was also assessed using a battery of upper limb
      function tests. RESULTS: In patients, FA( AH/UH) correlated positively with the
      slope of recruitment curves (RC(AH/UH)) and grip strength. FA(AH/UH) also
      correlated negatively with the silent period duration (SP(AH/UH)). According to
      the FA(AH/UH), patients were also classified into groups with minimal or
      extensive Wallerian degeneration (WD). Patients with more extensive WD had poorer
      grip strength, dexterity, and range of movement. CONCLUSIONS: The authors'
      results suggest that structural and functional integrity of the CFT is essential
      to maintain function of the upper limb after stroke.

PMID- 17507646
TI  - Probing the membrane environment of the TOR kinases reveals functional
      interactions between TORC1, actin, and membrane trafficking in Saccharomyces
      cerevisiae.
AB  - The TOR kinases are regulators of growth in eukaryotic cells that assemble into
      two distinct protein complexes, TORC1 and TORC2, where TORC1 is inhibited by the
      antibiotic rapamycin. Present models favor a view wherein TORC1 regulates cell
      mass accumulation, and TORC2 regulates spatial aspects of growth, including
      organization of the actin cytoskeleton. Here, we demonstrate that in yeast both
      TORC1 and TORC2 fractionate with a novel form of detergent-resistant membranes
      that are distinct from detergent-resistant plasma membrane "rafts." Proteomic
      analysis of these TOR-associated membranes revealed the presence of regulators of
      endocytosis and the actin cytoskeleton. Genetic analyses revealed a significant
      number of interactions between these components and TORC1, demonstrating a
      functional link between TORC1 and actin/endocytosis-related genes. Moreover, we
      found that inhibition of TORC1 by rapamycin 1) disrupted actin polarization, 2)
      delayed actin repolarization after glucose starvation, and 3) delayed
      accumulation of lucifer yellow within the vacuole. By combining our genetic
      results with database mining, we constructed a map of interactions that led to
      the identification of additional genetic interactions between TORC1 and
      components involved in membrane trafficking. Together, these results reveal the
      broad scope of cellular processes influenced by TORC1, and they underscore the
      functional overlap between TORC1 and TORC2.

PMID- 17507647
TI  - Myosin Vb interacts with Rab8a on a tubular network containing EHD1 and EHD3.
AB  - Cells use multiple pathways to internalize and recycle cell surface components.
      Although Rab11a and Myosin Vb are involved in the recycling of proteins
      internalized by clathrin-mediated endocytosis, Rab8a has been implicated in
      nonclathrin-dependent endocytosis and recycling. By yeast two-hybrid assays, we
      have now demonstrated that Myosin Vb can interact with Rab8a, but not Rab8b. We
      have confirmed the interaction of Myosin Vb with Rab11a and Rab8a in vivo by
      using fluorescent resonant energy transfer techniques. Rab8a and Myosin Vb
      colocalize to a tubular network containing EHD1 and EHD3, which does not contain
      Rab11a. Myosin Vb tail can cause the accumulation of both Rab11a and Rab8a in
      collapsed membrane cisternae, whereas dominant-negative Rab11-FIP2(129-512)
      selectively accumulates Rab11a but not Rab8a. Additionally, dynamic live cell
      imaging demonstrates distinct pathways for Rab11a and Rab8a vesicle trafficking.
      These findings indicate that Rab8a and Rab11a define different recycling pathways
      that both use Myosin Vb.

PMID- 17507648
TI  - Mesenchymal stem cells use integrin beta1 not CXC chemokine receptor 4 for
      myocardial migration and engraftment.
AB  - Recent evidence has demonstrated the importance of bone marrow-derived
      mesenchymal stem cells (BM-MSCs) in the repair of damaged myocardium. The
      molecular mechanisms of engraftment and migration of BM-MSCs in the ischemic
      myocardium are unknown. In this study, we developed a functional genomics
      approach toward the identification of mediators of engraftment and migration of
      BM-MSCs within the ischemic myocardium. Our strategy involves microarray
      profiling (>22,000 probes) of ischemic hearts, complemented by reverse
      transcription-polymerase chain reaction and fluorescence-activated cell sorting
      of corresponding adhesion molecule and cytokine receptors in BM-MSCs to focus on
      the coexpressed pairs only. Our data revealed nine complementary adhesion
      molecules and cytokine receptors, including integrin beta1, integrin alpha4, and
      CXC chemokine receptor 4 (CXCR4). To examine their functional contributions, we
      first blocked selectively these receptors by preincubation of BM-MSCs with
      specific neutralizing antibodies, and then we administered these cells
      intramyocardially. A significant reduction in the total number of BM-MSC in the
      infarcted myocardium was observed after integrin beta1 blockade but not integrin
      alpha4 or CXCR4 blockade. The latter observation is distinctively different from
      that reported for hematopoietic stem cells (HSCs). Thus, our data show that BM
      MSCs use a different pathway from HSCs for intramyocardial trafficking and
      engraftment.

PMID- 17507649
TI  - A developmentally regulated chaperone complex for the endoplasmic reticulum of
      male haploid germ cells.
AB  - Glycoprotein folding is mediated by lectin-like chaperones and protein disulfide
      isomerases (PDIs) in the endoplasmic reticulum. Calnexin and the PDI homologue
      ERp57 work together to help fold nascent polypeptides with glycans located toward
      the N-terminus of a protein, whereas PDI and BiP may engage proteins that lack
      glycans or have sugars toward the C-terminus. In this study, we show that the PDI
      homologue PDILT is expressed exclusively in postmeiotic male germ cells, in
      contrast to the ubiquitous expression of many other PDI family members in the
      testis. PDILT is induced during puberty and represents the first example of a PDI
      family member under developmental control. We find that PDILT is not active as an
      oxido-reductase, but interacts with the model peptide Delta-somatostatin and
      nonnative bovine pancreatic trypsin inhibitor in vitro, indicative of chaperone
      activity. In vivo, PDILT forms a tissue-specific chaperone complex with the
      calnexin homologue calmegin. The identification of a redox-inactive chaperone
      partnership defines a new system of testis-specific protein folding with
      implications for male fertility.

PMID- 17507650
TI  - The signal recognition particle (SRP) RNA links conformational changes in the SRP
      to protein targeting.
AB  - The RNA component of the signal recognition particle (SRP) is universally
      required for cotranslational protein targeting. Biochemical studies have shown
      that SRP RNA participates in the central step of protein targeting by catalyzing
      the interaction of the SRP with the SRP receptor (SR). SRP RNA also accelerates
      GTP hydrolysis in the SRP.SR complex once formed. Using a reverse-genetic and
      biochemical analysis, we identified mutations in the E. coli SRP protein, Ffh,
      that abrogate the activity of the SRP RNA and cause corresponding targeting
      defects in vivo. The mutations in Ffh that disrupt SRP RNA activity map to
      regions that undergo dramatic conformational changes during the targeting
      reaction, suggesting that the activity of the SRP RNA is linked to the major
      conformational changes in the signal sequence-binding subunit of the SRP. In this
      way, the SRP RNA may coordinate the interaction of the SRP and the SR with
      ribosome recruitment and transfer to the translocon, explaining why the SRP RNA
      is an indispensable component of the protein targeting machinery.

PMID- 17507652
TI  - Binding of CAP70 to inducible nitric oxide synthase and implications for the
      vectorial release of nitric oxide in polarized cells.
AB  - In this article we analyze the mechanisms by which the C-terminal four amino
      acids of inducible nitric oxide synthase (NOS2) interact with proteins that
      contain PDZ (PSD-95/DLG/ZO-1) domains resulting in the translocation of NOS2 to
      the cellular apical domain. It has been reported that human hepatic NOS2
      associates to EBP50, a protein with two PDZ domains present in epithelial cells.
      We describe herein that NOS2 binds through its four carboxy-terminal residues to
      CAP70, a protein that contains four PDZ modules that is targeted to apical
      membranes. Interestingly, this interaction augments both the cytochrome c
      reductase and .NO-synthase activities of NOS2. Binding of CAP70 to NOS2 also
      results in an increase in the population of active NOS2 dimers. In addition,
      CAP70 participates in the correct subcellular targeting of NOS2 in a process that
      is also dependent on the acylation state of the N-terminal end of NOS2. Hence,
      nonpalmitoylated NOS2 is unable to progress toward the apical side of the cell
      despite its interaction with either EBP50 or CAP70. Likewise, if we abrogate the
      interaction of NOS2 with either EBP50 or CAP70 by fusing the GFP reporter to the
      carboxy-terminal end of NOS2 palmitoylation is not sufficient to confer an apical
      targeting.

PMID- 17507651
TI  - Urokinase receptor cleavage: a crucial step in fibroblast-to-myofibroblast
      differentiation.
AB  - Fibroblasts migrate into and repopulate connective tissue wounds. At the wound
      edge, fibroblasts differentiate into myofibroblasts, and they promote wound
      closure. Regulated fibroblast-to-myofibroblast differentiation is critical for
      regenerative healing. Previous studies have focused on the role in fibroblasts of
      urokinase plasmingen activator/urokinase plasmingen activator receptor
      (uPA/uPAR), an extracellular protease system that promotes matrix remodeling,
      growth factor activation, and cell migration. Whereas fibroblasts have
      substantial uPA activity and uPAR expression, we discovered that cultured
      myofibroblasts eventually lost cell surface uPA/uPAR. This led us to investigate
      the relevance of uPA/uPAR activity to myofibroblast differentiation. We found
      that fibroblasts expressed increased amounts of full-length cell surface uPAR
      (D1D2D3) compared with myofibroblasts, which had reduced expression of D1D2D3 but
      increased expression of the truncated form of uPAR (D2D3) on their cell surface.
      Retaining full-length uPAR was found to be essential for regulating myofibroblast
      differentiation, because 1) protease inhibitors that prevented uPAR cleavage also
      prevented myofibroblast differentiation, and 2) overexpression of cDNA for a
      noncleavable form of uPAR inhibited myofibroblast differentiation. These data
      support a novel hypothesis that maintaining full-length uPAR on the cell surface
      regulates the fibroblast to myofibroblast transition and that down-regulation of
      uPAR is necessary for myofibroblast differentiation.

PMID- 17507653
TI  - Ets-2 repressor factor silences extrasynaptic utrophin by N-box mediated
      repression in skeletal muscle.
AB  - Utrophin is the autosomal homologue of dystrophin, the protein product of the
      Duchenne's muscular dystrophy (DMD) locus. Utrophin expression is temporally and
      spatially regulated being developmentally down-regulated perinatally and enriched
      at neuromuscular junctions (NMJs) in adult muscle. Synaptic localization of
      utrophin occurs in part by heregulin-mediated extracellular signal-regulated
      kinase (ERK)-phosphorylation, leading to binding of GABPalpha/beta to the N
      box/EBS and activation of the major utrophin promoter-A expressed in myofibers.
      However, molecular mechanisms contributing to concurrent extrasynaptic silencing
      that must occur to achieve NMJ localization are unknown. We demonstrate that the
      Ets-2 repressor factor (ERF) represses extrasynaptic utrophin-A in muscle. Gel
      shift and chromatin immunoprecipitation studies demonstrated physical association
      of ERF with the utrophin-A promoter N-box/EBS site. ERF overexpression repressed
      utrophin-A promoter activity; conversely, small interfering RNA-mediated ERF
      knockdown enhanced promoter activity as well as endogenous utrophin mRNA levels
      in cultured muscle cells in vitro. Laser-capture microscopy of tibialis anterior
      NMJ and extrasynaptic transcriptomes and gene transfer studies provide spatial
      and direct evidence, respectively, for ERF-mediated utrophin repression in vivo.
      Together, these studies suggest "repressing repressors" as a potential strategy
      for achieving utrophin up-regulation in DMD, and they provide a model for
      utrophin-A regulation in muscle.

PMID- 17507654
TI  - Bsr, a nuclear-retained RNA with monoallelic expression.
AB  - The imprinted Dlk1-Gtl2 and Prader-Willi syndrome (PWS) regions are characterized
      by a complex noncoding transcription unit spanning arrays of tandemly repeated
      C/D RNA genes. These noncoding RNAs (ncRNAs) are thought to play an essential but
      still poorly understood role. To better understand the intracellular fate of
      these large ncRNAs, fluorescence in situ hybridization was carried out at the rat
      Dlk1-Gtl2 domain. This locus contains a approximately 100-kb-long gene cluster
      comprising 86 homologous RBII-36 C/D RNA gene copies, all of them intron-encoded
      within the ncRNA gene Bsr. Here, we demonstrate that the Bsr gene is
      monoallelically expressed in primary rat embryonic fibroblasts as well as in
      hypothalamic neurons and yields a large amount of unspliced and spliced RNAs at
      the transcription site, mostly as elongated RNA signals. Surprisingly, spliced
      Bsr RNAs released from the transcription site mainly concentrate as numerous,
      stable nuclear foci that do not colocalize with any known subnuclear structures.
      On drug treatments, a fraction of Bsr RNA relocalizes to the cytoplasm and
      associates with stress granules (SGs), but not with P-bodies, pointing to a
      potential link between SGs and the metabolism of ncRNA. Thus, Bsr might represent
      a novel type of nuclear-retained transcript.

PMID- 17507655
TI  - Cytotoxic necrotizing factor 1 prevents apoptosis via the Akt/IkappaB kinase
      pathway: role of nuclear factor-kappaB and Bcl-2.
AB  - Cytotoxic necrotizing factor 1 (CNF1) is a protein toxin produced by some
      pathogenic strains of Escherichia coli that specifically activates Rho, Rac, and
      Cdc42 GTPases. We previously reported that this toxin prevents the ultraviolet-B
      induced apoptosis in epithelial cells, with a mechanism that remained to be
      defined. In this work, we show that the proteasomal degradation of the Rho GTPase
      is necessary to achieve cell death protection, because inhibition of Rho
      degradation abolishes the prosurvival activity of CNF1. We hypothesize that Rho
      inactivation allows the activity of Rac to become dominant. This in turn leads to
      stimulation of the phosphoinositide 3-kinase/Akt/IkappaB kinase/nuclear factor
      kappaB prosurvival pathway and to a remarkable modification in the architecture
      of the mitochondrial network, mainly consisting in the appearance of elongated
      and interconnected mitochondria. Importantly, we found that Bcl-2 silencing
      reduces the ability of CNF1 to protect cells against apoptosis and that it also
      prevents the CNF1-induced mitochondrial changes. It is worth noting that the
      ability of a bacterial toxin to induce such a remodeling of the mitochondrial
      network is herein reported for the first time. The possible pathophysiological
      relevance of this finding is discussed.

PMID- 17507656
TI  - Spc24 and Stu2 promote spindle integrity when DNA replication is stalled.
AB  - The kinetochore, a protein complex that links chromosomes to microtubules (MTs),
      is required to prevent spindle expansion during S phase in budding yeast, but the
      mechanism of how the kinetochore maintains integrity of the bipolar spindle
      before mitosis is not well understood. Here, we demonstrate that a mutation of
      Spc24, a component of the conserved Ndc80 kinetochore complex, causes lethality
      when cells are exposed to the DNA replication inhibitor hydroxyurea (HU) due to
      premature spindle expansion and segregation of incompletely replicated DNA.
      Overexpression of Stu1, a CLASP-related MT-associated protein or a truncated form
      of the XMAP215 orthologue Stu2 rescues spc24-9 HU lethality and prevents spindle
      expansion. Truncated Stu2 likely acts in a dominant-negative manner, because
      overexpression of full-length STU2 does not rescue spc24-9 HU lethality, and
      spindle expansion in spc24-9 HU-treated cells requires active Stu2. Stu1 and Stu2
      localize to the kinetochore early in the cell cycle and Stu2 kinetochore
      localization depends on Spc24. We propose that mislocalization of Stu2 results in
      premature spindle expansion in S phase stalled spc24-9 mutants. Identifying
      factors that restrain spindle expansion upon inhibition of DNA replication is
      likely applicable to the mechanism by which spindle elongation is regulated
      during a normal cell cycle.

PMID- 17507657
TI  - E-cadherin inhibits cell surface localization of the pro-migratory 5T4 oncofetal
      antigen in mouse embryonic stem cells.
AB  - Epithelial-mesenchymal transition (EMT) events occur during embryonic development
      and are important for the metastatic spread of epithelial tumors. We show here
      that spontaneous differentiation of mouse embryonic stem (ES) cells is associated
      with an E- to N-cadherin switch, up-regulation of E-cadherin repressor molecules
      (Snail and Slug proteins), gelatinase activity (matrix metalloproteinase [MMP]-2
      and -9), and increased cellular motility, all characteristic EMT events. The 5T4
      oncofetal antigen, previously shown to be associated with very early ES cell
      differentiation and altered motility, is also a part of this coordinated process.
      E- and N-cadherin and 5T4 proteins are independently regulated during ES cell
      differentiation and are not required for induction of EMT-associated transcripts
      and proteins, as judged from the study of the respective knockout ES cells.
      Further, abrogation of E-cadherin-mediated cell-cell contact in undifferentiated
      ES cells using neutralizing antibody results in a reversible mesenchymal
      phenotype and actin cytoskeleton rearrangement that is concomitant with
      translocation of the 5T4 antigen from the cytoplasm to the cell surface in an
      energy-dependent manner. E-cadherin null ES cells are constitutively cell surface
      5T4 positive, and although forced expression of E-cadherin cDNA in these cells is
      sufficient to restore cell-cell contact, cell surface expression of 5T4 antigen
      is unchanged. 5T4 and N-cadherin knockout ES cells exhibit significantly
      decreased motility during EMT, demonstrating a functional role for these proteins
      in this process. We conclude that E-cadherin protein stabilizes cortical actin
      cytoskeletal arrangement in ES cells, and this can prevent cell surface
      localization of the promigratory 5T4 antigen.

PMID- 17507658
TI  - Quantitative analysis of membrane remodeling at the phagocytic cup.
AB  - Nascent phagosomes, which are derived from the plasma membrane, acquire
      microbicidal properties through multiple fusion and fission events collectively
      known as maturation. Here we show that remodeling of the phagosomal membrane is
      apparent even before sealing, particularly when large particles are ingested.
      Fluorescent probes targeted to the plasma membrane are cleared from the region
      lining the particle before engulfment is completed. Extensive clearance was noted
      for components of the inner as well as outer monolayer of the plasmalemma.
      Segregation of lipid microdomains was ruled out as the mechanism underlying
      membrane remodeling, because markers residing in rafts and those that are
      excluded were similarly depleted. Selective endocytosis was also ruled out.
      Instead, several lines of evidence indicate that endomembranes inserted by
      exocytosis at sites of ingestion displace the original membrane constituents from
      the base of the phagosomal cup. The Fcgamma receptors that trigger phagocytosis
      remain associated with their ligands. By contrast, Src-family kinases that are
      the immediate effectors of receptor activation are flushed away from the cup by
      the incoming membranes. Together with the depletion of phosphoinositides required
      for signal transduction, the disengagement of receptors from their effectors by
      bulk membrane remodeling provides a novel means to terminate receptor signaling.

PMID- 17507659
TI  - Specific trans-acting proteins interact with auxiliary RNA polyadenylation
      elements in the COX-2 3'-UTR.
AB  - Two cyclooxygenase (COX) enzymes, COX-1 and COX-2, are present in human cells.
      While COX-1 is constitutively expressed, COX-2 is inducible and up-regulated in
      response to many signals. Since increased transcriptional activity accounts for
      only part of COX-2 up-regulation, we chose to explore other RNA processing
      mechanisms in the regulation of this gene. Previously, we showed that COX-2 is
      regulated by alternative polyadenylation, and that the COX-2 proximal
      polyadenylation signal contains auxiliary upstream sequence elements (USEs) that
      are very important in efficient polyadenylation. To explore trans-acting protein
      factors interacting with these cis-acting RNA elements, we performed pull-down
      assays with HeLa nuclear extract and biotinylated RNA oligonucleotides
      representing COX-2 USEs. We identified PSF, p54(nrb), PTB, and U1A as proteins
      specifically bound to the COX-2 USEs. We further explored their participation in
      polyadenylation using MS2 phage coat protein-MS2 RNA binding site tethering
      assays, and found that tethering any of these four proteins to the COX-2 USE
      mutant RNA can compensate for these cis-acting elements. Finally, we suggest that
      these proteins (p54(nrb), PTB, PSF, and U1A) may interact as a complex since
      immunoprecipitations of the transfected MS2 fusion proteins coprecipitate the
      other proteins.

PMID- 17507660
TI  - G-ribo motif favors the formation of pseudoknots in ribosomal RNA.
AB  - Analysis of the pseudoknots existing in the ribosomal RNA showed that four of
      them are formed with the help of G-ribo, a recently identified RNA recurrent
      motif. The analysis of these pseudoknots revealed two major aspects in the G-ribo
      motif structure, which together provide the structural context favoring the
      formation of two different types of pseudoknots. The first aspect pertains to a
      particular side-by-side juxtaposition of two double helices that facilitates
      switches of the polynucleotide chain between different strands. The second aspect
      deals with the presence of an adenosine at a specific place where it can
      stabilize a particular arrangement of two quasicoaxial helices required for the
      pseudoknot formation. Additional analysis shows that the latter aspect is also
      present in other pseudoknots not related to the G-ribo motif or the ribosome, and
      thus represents a general structural element favoring the formation of
      pseudoknots.

PMID- 17507661
TI  - Predicting helical coaxial stacking in RNA multibranch loops.
AB  - The hypothesis that RNA coaxial stacking can be predicted by free energy
      minimization using nearest-neighbor parameters is tested. The results show 58.2%
      positive predictive value (PPV) and 65.7% sensitivity for accuracy of the lowest
      free energy configuration compared with crystal structures. The probability of
      each stacking configuration can be predicted using a partition function
      calculation. Based on the dependence of accuracy on the calculated probability of
      the stacks, a probability threshold of 0.7 was chosen for predicting coaxial
      stacks. When scoring these likely stacks, the PPV was 66.7% at a sensitivity of
      51.9%. It is observed that the coaxial stacks of helices that are not separated
      by unpaired nucleotides can be predicted with a significantly higher accuracy
      (74.0% PPV, 66.1% sensitivity) than the coaxial stacks mediated by noncanonical
      base pairs (55.9% PPV, 36.5% sensitivity). It is also shown that the prediction
      accuracy does not show any obvious trend with multibranch loop complexity as
      measured by three different parameters.

PMID- 17507662
TI  - Hot spots of retroviral integration in human CD34+ hematopoietic cells.
AB  - Insertional oncogenesis is a possible consequence of the integration of gamma
      retroviral (RV) or lentiviral (LV) vectors into the human genome. RV common
      insertion sites (CISs) have been identified in hematopoietic malignancies and in
      the nonmalignant progeny of transduced hematopoietic stem/progenitor cells
      (HSCs), possibly as a consequence of clonal selection in vivo. We have mapped a
      large number of RV and LV integrations in human CD34(+) HSCs, transduced in vitro
      and analyzed without selection. Recurrent insertion sites (hot spots) account for
      more than 21% of the RV integration events, while they are significantly less
      frequent in the case of LV vectors. RV but not LV hot spots are highly enriched
      in proto-oncogenes, cancer-associated CISs, and growth-controlling genes,
      indicating that at least part of the biases observed in the HSC progeny in vivo
      are characteristics of RV integration, already present in nontransplanted cells.
      Genes involved in hematopoietic and immune system development are targeted at
      high frequency and enriched in hot spots, suggesting that the CD34(+) gene
      expression program is instrumental in directing RV integration. The lower
      propensity of LV vectors for integrating in potentially dangerous regions of the
      human genome may be a factor determining a better safety profile for gene therapy
      applications.

PMID- 17507663
TI  - p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not pre
      TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis.
AB  - Inactivation of the CDKN2 genes that encode the p16(INK4A) and p14(ARF) proteins
      occurs in the majority of human T-cell acute lymphoblastic leukemias (T-ALLs).
      Ectopic expression of TAL1 and LMO1 genes is linked to the development of T-ALL
      in humans. In TAL1xLMO1 mice, leukemia develops in 100% of mice at 5 months. To
      identify the molecular events crucial to leukemic transformation, we produced
      several mouse models. We report here that expression of P16(INK4A) in developing
      TAL1xLMO1 thymocytes blocks leukemogenesis in the majority of the mice, and the
      leukemias that eventually develop show P16(INK4A) loss of expression. Events
      related to the T-cell receptor beta selection process are thought to be important
      for leukemic transformation. We show here that the absence of the pTalpha chain
      only slightly delays the appearance of TAL1xLMO1-induced T-ALL, which indicates a
      minor role of the pTalpha chain. We also show that the CD3epsilon-mediated signal
      transduction pathway is essential for this transformation process, since the
      TAL1xLMO1xCD3epsilon-deficient mice do not develop T-ALL for up to 1 year.

PMID- 17507664
TI  - Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta
      artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease.
AB  - Adoptive transfer of Epstein Barr virus (EBV)-specific cytotoxic T-lymphocytes
      (EBV-CTLs) has shown that these cells persist in patients with EBV(+) Hodgkin
      lymphoma (HD) to produce complete tumor responses. Treatment failure, however,
      occurs if a subpopulation of malignant cells in the tumor lacks or loses
      expression of EBV antigens. We have therefore determined whether we could prepare
      EBV-CTLs that retained the antitumor activity conferred by their native receptor
      while expressing a chimeric antigen receptor (CAR) specific for CD30, a molecule
      highly and consistently expressed on malignant Hodgkin Reed-Sternberg cells. We
      made a CD30CAR and were able to express it on 26% (+/- 11%) and 22% (+/- 5%) of
      EBV-CTLs generated from healthy donors and HD patients, respectively. These
      CD30CAR(+) CTLs killed both autologous EBV(+) cells through their native receptor
      and EBV(-)/CD30(+) targets through their major histocompatibility complex (MHC)
      unrestricted CAR. A subpopulation of activated T cells also express CD30, but the
      CD30CAR(+) CTLs did not impair cellular immune responses, probably because normal
      T cells express lower levels of the target antigen. In a xenograft model,
      CD30CAR(+) EBV-CTLs could be costimulated by EBV-infected cells and produce
      antitumor effects even against EBV(-)/CD30(+) tumors. EBV-CTLs expressing both a
      native and a chimeric antigen receptor may therefore have added value for
      treatment of HD.

PMID- 17507665
TI  - Glutathione redox regulates airway hyperresponsiveness and airway inflammation in
      mice.
AB  - Glutathione is the major intracellular redox buffer. We have shown that
      glutathione redox status, which is the balance between intracellular reduced
      (GSH) and oxidized (GSSG) glutathione, in antigen-presenting cells (APC)
      regulates the helper T cell type 1 (Th1)/Th2 balance due to the production of IL
      12. Bronchial asthma is a typical Th2 disease. Th2 cells and Th2 cytokines are
      characteristic of asthma and trigger off an inflammation. Accordingly, we studied
      the effects of the intracellular glutathione redox status on airway
      hyperresponsiveness (AHR) and allergen-induced airway inflammation in a mouse
      model of asthma. We used gamma-Glutamylcysteinylethyl ester (gamma-GCE), which is
      a membrane-permeating GSH precursor, to elevate the intracellular GSH level and
      GSH/GSSG ratio of mice. In vitro, gamma-GCE pretreatment of human monocytic THP-1
      cells elevated the GSH/GSSG ratio and enhanced IL-12(p70) production induced by
      LPS. In the mouse asthma model, intraperitoneal injection of gamma-GCE elevated
      the GSH/GSSG ratio of lung tissue and reduced AHR. gamma-GCE reduced levels of IL
      4, IL-5, IL-10, and the chemokines eotaxin and RANTES (regulated on activation,
      normal T cell expressed and secreted) in bronchoalveolar lavage fluid, whereas it
      enhanced the production of IL-12 and IFN-gamma. Histologically, gamma-GCE
      suppressed eosinophils infiltration. Interestingly, we also found that gamma-GCE
      directly inhibited chemokine-induced eosinophil chemotaxis without affecting
      eotaxin receptor chemokine receptor 3 (CCR3) expressions. Taken together, these
      findings suggest that changing glutathione redox balance, increase in GSH level,
      and the GSH/GSSG ratio by gamma-GCE, ameliorate bronchial asthma by altering the
      Th1/Th2 imbalance through IL-12 production from APC and suppressing chemokine
      production and eosinophil migration itself.

PMID- 17507666
TI  - Differential expression and oxidation of MKP-1 modulates TNF-alpha gene
      expression.
AB  - Monocytic cells are integral in the pathogenesis of inflammatory disorders. We
      have shown previously that asbestos-induced p38 mitogen-activated protein (MAP)
      kinase activation and TNF-alpha expression are mediated by H(2)O(2) in blood
      monocytes. Due to the high expression and activity of catalase and glutathione
      peroxidase, normal alveolar macrophages do not respond in a manner similar to
      that of blood monocytes. Since kinase activity is tightly regulated by
      phosphatases, we hypothesized that the dual specificity phosphatase MAP kinase
      phosphatase (MKP)-1 regulates p38 activity and TNF-alpha production in alveolar
      macrophages due to insufficient H(2)O(2) generation in response to asbestos. We
      found that MKP-1 was highly expressed in alveolar macrophages, while blood
      monocytes had minimal expression. Inhibition of expression and activity of MKP-1
      or overexpression of a catalytic mutant MKP-1 recovered p38 activity in alveolar
      macrophages. We questioned whether MKP-1 oxidation played a role dictating the
      contrasting responses of these cells to asbestos exposure, and found that
      overexpressed wild-type MKP-1 in monocytes was oxidized, while the mutant MKP-1
      remained in the reduced form. Monocytes overexpressing either catalase or wild
      type MKP-1 had decreased p38 activation and TNF-alpha production, respectively.
      In addition, TNF-alpha gene expression was regained in alveolar macrophages
      overexpressing the catalytic mutant MKP-1. These data suggest that MKP-1, through
      increased expression and lack of oxidation, modulates the inflammatory response
      in alveolar macrophages exposed to asbestos.

PMID- 17507667
TI  - Long oligonucleotide microarrays for African green monkey gene expression profile
      analysis.
AB  - Nonhuman primates, including African green monkey (AGM), are important models for
      biomedical research. The information on monkey genomes is still limited and no
      versatile gene expression screening tool is available. We tested human whole
      genome microarrays for cross-species reactivity with AGM transcripts using both
      long oligonucleotide arrays (60-mer probes) and short oligonucleotide arrays (25
      mer). Using the long oligonucleotide arrays, we detected 4-fold more AGM
      transcripts than with the short oligonucleotide technology. The number of
      detected transcripts was comparable to that detected using human RNA, with 87% of
      the detected genes being shared between both species. The specificity of the
      signals obtained with the long oligonucleotide arrays was determined by analyzing
      the transcriptome of concanavalin A-activated CD4+ T cells vs. nonactivated T
      cells of two monkey species AGM and macaque. For both species, the genes showing
      the most significant changes in expression, such as IL-2R, were those known to be
      regulated in human CD4+ T cell activation. Finally, tissue specificity of the
      signals was established by comparing the transcription profiles of AGM brain and
      tonsil cells. In conclusion, the ABI human microarray platform provides a highly
      valuable tool for the assessment of AGM gene expression profiles.

PMID- 17507668
TI  - Thrombospondin-1 promotes cellular adherence of gram-positive pathogens via
      recognition of peptidoglycan.
AB  - Thrombospondin-1 (TSP1) is a matricellular glycoprotein that has key roles in
      interactions between human cells and components of the extracellular matrix. Here
      we report a novel role for the lectin TSP1 in pathogen-host interactions. Binding
      assays and flow cytometric analysis demonstrate that Streptococcus pneumoniae and
      other gram-positive pathogens including S. pyogenes, Staphylococcus aureus, and
      Listeria monocytogenes interact specifically with human TSP1. We also show for
      the first time that host cell-bound TSP1 promotes adherence of gram-positive
      pathogens to human epithelial and endothelial cell lines. Pretreatment of
      bacteria with sodium periodate but not Pronase E substantially reduced TSP1
      mediated bacterial adherence to host cells, suggesting that a glycoconjugate on
      the bacterial cell surface functions as the receptor for TSP1. Lipoteichoic acids
      did not affect TSP1-mediated adherence of S. pneumoniae to host cells. In
      contrast, attachment of S. pneumoniae and other gram-positive pathogens to host
      cells via TSP1 was blocked by soluble peptidoglycan, indicating recognition of
      bacterial peptidoglycan by TSP1. In conclusion, our results demonstrate that
      recognition of gram-positive pathogens by TSP1 promotes bacterial colonization of
      host tissue cells. In this scenario, peptidoglycan functions as adhesin and TSP1
      acts as a molecular bridge linking gram-positive bacteria with receptors on the
      host cell.

PMID- 17507669
TI  - The in silico map-based cloning of Pi36, a rice coiled-coil nucleotide-binding
      site leucine-rich repeat gene that confers race-specific resistance to the blast
      fungus.
AB  - The indica rice variety Kasalath carries Pi36, a gene that determines resistance
      to Chinese isolates of rice blast and that has been located to a 17-kb interval
      on chromosome 8. The genomic sequence of the reference japonica variety
      Nipponbare was used for an in silico prediction of the resistance (R) gene
      content of the interval and hence for the identification of candidate gene(s) for
      Pi36. Three such sequences, which all had both a nucleotide-binding site and a
      leucine-rich repeat motif, were present. The three candidate genes were amplified
      from the genomic DNA of a number of varieties by long-range PCR, and the
      resulting amplicons were inserted into pCAMBIA1300 and/or pYLTAC27 vectors to
      determine sequence polymorphisms correlated to the resistance phenotype and to
      perform transgenic complementation tests. Constructs containing each candidate
      gene were transformed into the blast-susceptible variety Q1063, which allowed the
      identification of Pi36-3 as the functional gene, with the other two candidates
      being probable pseudogenes. The Pi36-encoded protein is composed of 1056 amino
      acids, with a single substitution event (Asp to Ser) at residue 590 associated
      with the resistant phenotype. Pi36 is a single-copy gene in rice and is more
      closely related to the barley powdery mildew resistance genes Mla1 and Mla6 than
      to the rice blast R genes Pita, Pib, Pi9, and Piz-t. An RT-PCR analysis showed
      that Pi36 is constitutively expressed in Kasalath.

PMID- 17507670
TI  - Correcting for measurement error in individual ancestry estimates in structured
      association tests.
AB  - We present theoretical explanations and show through simulation that the
      individual admixture proportion estimates obtained by using ancestry informative
      markers should be seen as an error-contaminated measurement of the underlying
      individual ancestry proportion. These estimates can be used in structured
      association tests as a control variable to limit type I error inflation or reduce
      loss of power due to population stratification observed in studies of admixed
      populations. However, the inclusion of such error-containing variables as
      covariates in regression models can bias parameter estimates and reduce ability
      to control for the confounding effect of admixture in genetic association tests.
      Measurement error correction methods offer a way to overcome this problem but
      require an a priori estimate of the measurement error variance. We show how an
      upper bound of this variance can be obtained, present four measurement error
      correction methods that are applicable to this problem, and conduct a simulation
      study to compare their utility in the case where the admixed population results
      from the intermating between two ancestral populations. Our results show that the
      quadratic measurement error correction (QMEC) method performs better than the
      other methods and maintains the type I error to its nominal level.

PMID- 17507671
TI  - Prediction of multilocus identity-by-descent.
AB  - Previous studies have enabled exact prediction of probabilities of identity-by
      descent (IBD) in random-mating populations for a few loci (up to four or so),
      with extension to more using approximate regression methods. Here we present a
      precise predictor of multiple-locus IBD using simple formulas based on exact
      results for two loci. In particular, the probability of non-IBD X(ABC) at each of
      ordered loci A, B, and C can be well approximated by X(ABC) = X(AB)X(BC)/X(B) and
      generalizes to X(123...k) = X(12)X(23...)X(k)(-1,k)/X(k-2), where X is the
      probability of non-IBD at each locus. Predictions from this chain rule are very
      precise with population bottlenecks and migration, but are rather poorer in the
      presence of mutation. From these coefficients, the probabilities of multilocus
      IBD and non-IBD can also be computed for genomic regions as functions of
      population size, time, and map distances. An approximate but simple recurrence
      formula is also developed, which generally is less accurate than the chain rule
      but is more robust with mutation. Used together with the chain rule it leads to
      explicit equations for non-IBD in a region. The results can be applied to
      detection of quantitative trait loci (QTL) by computing the probability of IBD at
      candidate loci in terms of identity-by-state at neighboring markers.

PMID- 17507673
TI  - Impact of interpopulation divergence on additive and dominance variance in hybrid
      populations.
AB  - We present a theoretical proof that the ratio of the dominance vs. the additive
      variance decreases with increasing genetic divergence between two populations.
      While the dominance variance is the major component of the variance due to
      specific combining ability (sigma(SCA)(2)), the additive variance is the major
      component of the variance due to general combining ability (sigma(GCA)(2)).
      Therefore, we conclude that interpopulation improvement becomes more efficient
      with divergent than with genetically similar heterotic groups, because
      performance of superior hybrids can be predicted on the basis of general
      combining ability effects.

PMID- 17507672
TI  - Ure2p function is enhanced by its prion domain in Saccharomyces cerevisiae.
AB  - The Ure2 protein of Saccharomyces cerevisiae can become a prion (infectious
      protein). At very low frequencies Ure2p forms an insoluble, infectious amyloid
      known as [URE3], which is efficiently transmitted to progeny cells or mating
      partners that consequently lose the normal Ure2p nitrogen regulatory function.
      The [URE3] prion causes yeast cells to grow slowly, has never been identified in
      the wild, and confers no obvious phenotypic advantage. An N-terminal asparagine
      rich domain determines Ure2p prion-forming ability. Since ure2Delta strains are
      complemented by plasmids that overexpress truncated forms of Ure2p lacking the
      prion domain, the existence of the [URE3] prion and the evolutionary conservation
      of an N-terminal extension have remained mysteries. We find that Ure2p function
      is actually compromised in vivo by truncation of the prion domain. Moreover,
      Ure2p stability is diminished without the full-length prion domain. Mca1p, like
      Ure2p, has an N-terminal Q/N-rich domain whose deletion reduces its steady-state
      levels. Finally, we demonstrate that the prion domain may affect the interaction
      of Ure2p with other components of the nitrogen regulation system, specifically
      the negative regulator of nitrogen catabolic genes, Gzf3p.

PMID- 17507674
TI  - Defective decapentaplegic signaling results in heart overgrowth and reduced
      cardiac output in Drosophila.
AB  - During germ-band extension, Decapentaplegic (Dpp) signals from the dorsal
      ectoderm to maintain Tinman (Tin) expression in the underlying mesoderm. This
      signal specifies the cardiac field, and homologous genes (BMP2/4 and Nkx2.5)
      perform this function in mammals. We showed previously that a second Dpp signal
      from the dorsal ectoderm restricts the number of pericardial cells expressing the
      transcription factor Zfh1. Here we report that, via Zfh1, the second Dpp signal
      restricts the number of Odd-skipped-expressing and the number of Tin-expressing
      pericardial cells. Dpp also represses Tin expression independently of Zfh1,
      implicating a feed-forward mechanism in the regulation of Tin pericardial cell
      number. In the adjacent dorsal muscles, Dpp has the opposite effect. Dpp
      maintains Kruppel and Even-skipped expression required for muscle development.
      Our data show that Dpp refines the cardiac field by limiting the number of
      pericardial cells. This maintains the boundary between pericardial and dorsal
      muscle cells and defines the size of the heart. In the absence of the second Dpp
      signal, pericardial cells overgrow and this significantly reduces larval cardiac
      output. Our study suggests the existence of a second round of BMP signaling in
      mammalian heart development and that perhaps defects in this signal play a role
      in congenital heart defects.

PMID- 17507676
TI  - A validated whole-genome association study of efficient food conversion in
      cattle.
AB  - The genetic factors that contribute to efficient food conversion are largely
      unknown. Several physiological systems are likely to be important, including
      basal metabolic rate, the generation of ATP, the regulation of growth and
      development, and the homeostatic control of body mass. Using whole-genome
      association, we found that DNA variants in or near proteins contributing to the
      background use of energy of the cell were 10 times as common as those affecting
      appetite and body-mass homeostasis. In addition, there was a genic contribution
      from the extracellular matrix and tissue structure, suggesting a trade-off
      between efficiency and tissue construction. Nevertheless, the largest group
      consisted of those involved in gene regulation or control of the phenotype. We
      found that the distribution of micro-RNA motifs was significantly different for
      the genetic variants associated with residual feed intake than for the genetic
      variants in total, although the distribution of promoter sequence motifs was not
      different. This suggests that certain subsets of micro-RNA are more important for
      the regulation of this trait. Successful validation depended on the sign of the
      allelic association in different populations rather than on the strength of the
      initial association or its size of effect.

PMID- 17507675
TI  - A rho-binding protein kinase C-like activity is required for the function of
      protein kinase N in Drosophila development.
AB  - The Rho GTPases interact with multiple downstream effectors to exert their
      biological functions, which include important roles in tissue morphogenesis
      during the development of multicellular organisms. Among the Rho effectors are
      the protein kinase N (PKN) proteins, which are protein kinase C (PKC)-like
      kinases that bind activated Rho GTPases. The PKN proteins are well conserved
      evolutionarily, but their biological role in any organism is poorly understood.
      We previously determined that the single Drosophila ortholog of mammalian PKN
      proteins, Pkn, is a Rho/Rac-binding kinase essential for Drosophila development.
      By performing "rescue" studies with various Pkn mutant constructs, we have
      defined the domains of Pkn required for its role during Drosophila development.
      These studies suggested that Rho, but not Rac binding is important for Pkn
      function in development. In addition, we determined that the kinase domain of
      PKC53E, a PKC family kinase, can functionally substitute for the kinase domain of
      Pkn during development, thereby exemplifying the evolutionary strategy of
      "combining" functional domains to produce proteins with distinct biological
      activities. Interestingly, we also identified a requirement for Pkn in wing
      morphogenesis, thereby revealing the first postembryonic function for Pkn.

PMID- 17507677
TI  - Regional control of chromatin organization by noncoding roX RNAs and the NURF
      remodeling complex in Drosophila melanogaster.
AB  - Dosage compensation in Drosophila is mediated by a histone-modifying complex that
      upregulates transcription of genes on the single male X chromosome. The male
      specific lethal (MSL) complex contains at least five proteins and two noncoding
      roX (RNA on X) RNAs. The mechanism by which the MSL complex targets the X
      chromosome is not understood. Here we use a sensitized system to examine the
      function of roX genes on the X chromosome. In mutants that lack the NURF
      nucleosome remodeling complex, the male polytene X chromosome is severely
      distorted, appearing decondensed. This aberrant morphology is dependent on the
      MSL complex. Strikingly, roX mutations suppress the Nurf mutant phenotype
      regionally on the male X chromosome. Furthermore, a roX transgene induces
      disruption of local flanking autosomal chromatin in Nurf mutants. Taken together,
      these results demonstrate the potent capability of roX genes to organize large
      chromatin domains in cis, on the X chromosome. In addition to interacting
      functions at the level of chromosome morphology, we also find that NURF complex
      and MSL proteins have opposing effects on roX RNA transcription. Together, these
      results demonstrate the importance of a local balance between modifying
      activities that promote and antagonize chromatin compaction within defined
      chromatin domains in higher organisms.

PMID- 17507678
TI  - The formation of the polyploid hybrids from different subfamily fish crossings
      and its evolutionary significance.
AB  - This study provides genetic evidences at the chromosome, DNA content, DNA
      fragment and sequence, and morphological levels to support the successful
      establishment of the polyploid hybrids of red crucian carp x blunt snout bream,
      which belonged to a different subfamily of fish (Cyprininae subfamily and
      Cultrinae subfamily) in the catalog. We successfully obtained the sterile
      triploid hybrids and bisexual fertile tetraploid hybrids of red crucian carp
      (RCC) (female symbol) x blunt snout bream (BSB) (male symbol) as well as their
      pentaploid hybrids. The triploid hybrids possessed 124 chromosomes with two sets
      from RCC and one set from BSB; the tetraploid hybrids had 148 chromosomes with
      two sets from RCC and two sets from BSB. The females of tetraploid hybrids
      produced unreduced tetraploid eggs that were fertilized with the haploid sperm of
      BSB to generate pentaploid hybrids with 172 chromosomes with three sets from BSB
      and two sets from RCC. The ploidy levels of triploid, tetraploid, and pentaploid
      hybrids were confirmed by counting chromosomal number, forming chromosomal
      karyotype, and measuring DNA content and erythrocyte nuclear volume. The similar
      and different DNA fragments were PCR amplified and sequenced in triploid,
      tetraploid hybrids, and their parents, indicating their molecular genetic
      relationship and genetic markers. In addition, this study also presents results
      about the phenotypes and feeding habits of polyploid hybrids and discusses the
      formation mechanism of the polyploid hybrids. It is the first report on the
      formation of the triploid, tetraploid, and pentaploid hybrids by crossing parents
      with a different chromosome number in vertebrates. The formation of the polyploid
      hybrids is potentially interesting in both evolution and fish genetic breeding.

PMID- 17507679
TI  - Patterns of molecular variation and evolution in Drosophila americana and its
      relatives.
AB  - We present the results of a survey of DNA sequence variability at X-linked and
      autosomal loci in Drosophila americana and of patterns of DNA sequence evolution
      among D. americana and four other related species in the virilis group of
      Drosophila. D. americana shows a typical level of silent polymorphism for a
      Drosophila species, but has an unusually low ratio of nonsynonymous to silent
      variation. Both D. virilis and D. americana also show a low ratio of
      nonsynonymous to synonymous substitutions along their respective lineages since
      the split from their common ancestor. The proportion of amino acid substitutions
      between D. americana and its relatives that are caused by positive selection, as
      estimated by extensions of the McDonald-Kreitman test, appears to be unusually
      high. We cannot, however, exclude the possibility that this reflects a recent
      increase in the intensity of selection on nonsynonymous mutations in D. americana
      and D. virilis. We also find that base composition at neutral sites appears to be
      in overall equilibrium among these species, but there is evidence for departure
      from equilibrium for codon usage in some lineages.

PMID- 17507680
TI  - Bayesian mapping of genomewide interacting quantitative trait loci for ordinal
      traits.
AB  - Development of statistical methods and software for mapping interacting QTL has
      been the focus of much recent research. We previously developed a Bayesian model
      selection framework, based on the composite model space approach, for mapping
      multiple epistatic QTL affecting continuous traits. In this study we extend the
      composite model space approach to complex ordinal traits in experimental crosses.
      We jointly model main and epistatic effects of QTL and environmental factors on
      the basis of the ordinal probit model (also called threshold model) that assumes
      a latent continuous trait underlies the generation of the ordinal phenotypes
      through a set of unknown thresholds. A data augmentation approach is developed to
      jointly generate the latent data and the thresholds. The proposed ordinal probit
      model, combined with the composite model space framework for continuous traits,
      offers a convenient way for genomewide interacting QTL analysis of ordinal
      traits. We illustrate the proposed method by detecting new QTL and epistatic
      effects for an ordinal trait, dead fetuses, in a F(2) intercross of mice. Utility
      and flexibility of the method are also demonstrated using a simulated data set.
      Our method has been implemented in the freely available package R/qtlbim, which
      greatly facilitates the general usage of the Bayesian methodology for genomewide
      interacting QTL analysis for continuous, binary, and ordinal traits in
      experimental crosses.

PMID- 17507681
TI  - The genomic landscape of short insertion and deletion polymorphisms in the
      chicken (Gallus gallus) Genome: a high frequency of deletions in tandem
      duplicates.
AB  - It is increasingly recognized that insertions and deletions (indels) are an
      important source of genetic as well as phenotypic divergence and diversity. We
      analyzed length polymorphisms identified through partial (0.25x) shotgun
      sequencing of three breeds of domestic chicken made by the International Chicken
      Polymorphism Map Consortium. A data set of 140,484 short indel polymorphisms in
      unique DNA was identified after filtering for microsatellite structures. There
      was a significant excess of tandem duplicates at indel sites, with deletions of a
      duplicate motif outnumbering the generation of duplicates through insertion.
      Indel density was lower in microchromosomes than in macrochromosomes, in the Z
      chromosome than in autosomes, and in 100 bp of upstream sequence, 5'-UTR, and
      first introns than in intergenic DNA and in other introns. Indel density was
      highly correlated with single nucleotide polymorphism (SNP) density. The mean
      density of indels in pairwise sequence comparisons was 1.9 x 10(-4) indel
      events/bp, approximately 5% the density of SNPs segregating in the chicken
      genome. The great majority of indels involved a limited number of nucleotides
      (median 1 bp), with A-rich motifs being overrepresented at indel sites. The
      overrepresentation of deletions at tandem duplicates indicates that replication
      slippage in duplicate sequences is a common mechanism behind indel mutation. The
      correlation between indel and SNP density indicates common effects of mutation
      and/or selection on the occurrence of indels and point mutations.

PMID- 17507682
TI  - Contrasting effects of in vitro fertilization and nuclear transfer on the
      expression of mtDNA replication factors.
AB  - Mitochondrial DNA (mtDNA) is normally only inherited through the oocyte. However,
      nuclear transfer (NT), the fusion of a donor cell with an enucleated oocyte, can
      transmit both donor cell and recipient oocyte mtDNA. mtDNA replication is under
      the control of nuclear-encoded replication factors, such as polymerase gamma
      (POLG) and mitochondrial transcription factor A (TFAM). These are first expressed
      during late preimplantation embryo development. To account for the persistence of
      donor cell mtDNA, even when introduced at residual levels (mtDNA(R)), we
      hypothesized that POLG and TFAM would be upregulated in intra- and interspecific
      (ovine-ovine) and intergeneric (caprine-ovine) NT embryos when compared to in
      vitro fertilized (IVF) embryos. For the intra- and interspecific crosses, PolGA
      (catalytic subunit), PolGB (accessory subunit), and TFAM mRNA were expressed at
      the 2-cell stage in both nondepleted (mtDNA(+)) and mtDNA(R) embryos with protein
      being expressed up to the 16-cell stage for POLGA and TFAM. However, at the 16
      cell stage, there was significantly more PolGA expression in the mtDNA(R) embryos
      compared to their mtDNA(+) counterparts. Expression for all three genes first
      matched IVF embryos at the blastocyst stage. In the intergeneric model, POLG was
      upregulated during preimplantation development. Although these embryos did not
      persist further than the 16+-cell stage, significantly more mtDNA(R) embryos
      reached this stage. However, the vast majority of these embryos were homoplasmic
      for recipient oocyte mtDNA. The upreglation in mtDNA replication factors was most
      likely due to the donor cells still expressing these factors prior to NT.

PMID- 17507683
TI  - Multiple functions of Drosophila BLM helicase in maintenance of genome stability.
AB  - Bloom Syndrome, a rare human disorder characterized by genomic instability and
      predisposition to cancer, is caused by mutation of BLM, which encodes a RecQ
      family DNA helicase. The Drosophila melanogaster ortholog of BLM, DmBlm, is
      encoded by mus309. Mutations in mus309 cause hypersensitivity to DNA-damaging
      agents, female sterility, and defects in repairing double-strand breaks (DSBs).
      To better understand these phenotypes, we isolated novel mus309 alleles.
      Mutations that delete the N terminus of DmBlm, but not the helicase domain, have
      DSB repair defects as severe as those caused by null mutations. We found that
      female sterility is due to a requirement for DmBlm in early embryonic cell
      cycles; embryos lacking maternally derived DmBlm have anaphase bridges and other
      mitotic defects. These defects were less severe for the N-terminal deletion
      alleles, so we used one of these mutations to assay meiotic recombination.
      Crossovers were decreased to about half the normal rate, and the remaining
      crossovers were evenly distributed along the chromosome. We also found that
      spontaneous mitotic crossovers are increased by several orders of magnitude in
      mus309 mutants. These results demonstrate that DmBlm functions in multiple
      cellular contexts to promote genome stability.

PMID- 17507685
TI  - Locating multiple interacting quantitative trait Loci using rank-based model
      selection.
AB  - In previous work, a modified version of the Bayesian information criterion (mBIC)
      was proposed to locate multiple interacting quantitative trait loci (QTL).
      Simulation studies and real data analysis demonstrate good properties of the mBIC
      in situations where the error distribution is approximately normal. However, as
      with other standard techniques of QTL mapping, the performance of the mBIC
      strongly deteriorates when the trait distribution is heavy tailed or when the
      data contain a significant proportion of outliers. In the present article, we
      propose a suitable robust version of the mBIC that is based on ranks. We
      investigate the properties of the resulting method on the basis of theoretical
      calculations, computer simulations, and a real data analysis. Our simulation
      results show that for the sample sizes typically used in QTL mapping, the methods
      based on ranks are almost as efficient as standard techniques when the data are
      normal and are much better when the data come from some heavy-tailed distribution
      or include a proportion of outliers.

PMID- 17507684
TI  - A maternal screen for genes regulating Drosophila oocyte polarity uncovers new
      steps in meiotic progression.
AB  - Meiotic checkpoints monitor chromosome status to ensure correct homologous
      recombination, genomic integrity, and chromosome segregation. In Drosophila, the
      persistent presence of double-strand DNA breaks (DSB) activates the ATR/Mei-41
      checkpoint, delays progression through meiosis, and causes defects in DNA
      condensation of the oocyte nucleus, the karyosome. Checkpoint activation has also
      been linked to decreased levels of the TGFalpha-like molecule Gurken, which
      controls normal eggshell patterning. We used this easy-to-score eggshell
      phenotype in a germ-line mosaic screen in Drosophila to identify new genes
      affecting meiotic progression, DNA condensation, and Gurken signaling. One
      hundred eighteen new ventralizing mutants on the second chromosome fell into 17
      complementation groups. Here we describe the analysis of 8 complementation
      groups, including Kinesin heavy chain, the SR protein kinase cuaba, the cohesin
      related gene dPds5/cohiba, and the Tudor-domain gene montecristo. Our findings
      challenge the hypothesis that checkpoint activation upon persistent DSBs is
      exclusively mediated by ATR/Mei-41 kinase and instead reveal a more complex
      network of interactions that link DSB formation, checkpoint activation, meiotic
      delay, DNA condensation, and Gurken protein synthesis.

PMID- 17507686
TI  - The PLEXIN PLX-2 and the ephrin EFN-4 have distinct roles in MAB-20/Semaphorin 2A
      signaling in Caenorhabditis elegans morphogenesis.
AB  - Semaphorins are extracellular proteins that regulate axon guidance and
      morphogenesis by interacting with a variety of cell surface receptors. Most
      semaphorins interact with plexin-containing receptor complexes, although some
      interact with non-plexin receptors. Class 2 semaphorins are secreted molecules
      that control axon guidance and epidermal morphogenesis in Drosophila and
      Caenorhabditis elegans. We show that the C. elegans class 2 semaphorin MAB-20
      binds the plexin PLX-2. plx-2 mutations enhance the phenotypes of hypomorphic mab
      20 alleles but not those of mab-20 null alleles, indicating that plx-2 and mab-20
      act in a common pathway. Both mab-20 and plx-2 mutations affect epidermal
      morphogenesis during embryonic and in postembryonic development. In both
      contexts, plx-2 null mutant phenotypes are much less severe than mab-20 null
      phenotypes, indicating that PLX-2 is not essential for MAB-20 signaling.
      Mutations in the ephrin efn-4 do not synergize with mab-20, indicating that EFN-4
      may act in MAB-20 signaling. EFN-4 and PLX-2 are coexpressed in the late
      embryonic epidermis where they play redundant roles in MAB-20-dependent cell
      sorting.

PMID- 17507688
TI  - Simvastatin inhibits IFN-gamma-induced CD40 gene expression by suppressing STAT
      1alpha.
AB  - CD40, a member of the TNF receptor superfamily, is critical for productive immune
      responses. Macrophages constitutively express CD40 at low levels, which are
      enhanced by IFN-gamma. IFN-gamma-induced CD40 expression involves activation of
      STAT-1alpha as well as NF-kappaB activation through an autocrine response to IFN
      gamma-induced TNF-alpha production. Statins are 3-hydroxy-3-methylglutaryl (HMG)
      CoA reductase inhibitors, which exert anti-inflammatory effects independent of
      their cholesterol-lowering actions. Herein, we describe that simvastatin (SS)
      inhibits IFN-gamma-induced CD40 expression via the suppression of STAT-1alpha
      expression. This results in diminished STAT-1alpha recruitment to the CD40
      promoter upon IFN-gamma treatment, in addition to reduced RNA Polymerase II
      recruitment and diminished levels of H3 and H4 histone acetylation. SS-mediated
      inhibition of STAT-1alpha occurs through suppression of constitutive STAT-1alpha
      mRNA and protein expression. The inhibitory effect of SS on CD40 and STAT-1alpha
      is dependent on HMG-CoA reductase activity, as the addition of mevalonate
      reverses the inhibitory effect. In addition, CD40 and/or STAT-1alpha expression
      is inhibited by GGTI-298 or Clostridium difficile Toxin A, a specific inhibitor
      of Rho family protein prenylation, indicating the involvement of small GTP
      binding proteins in this process. Collectively, these data indicate that SS
      inhibits IFN-gamma-induced CD40 expression by suppression of STAT-1alpha, and
      altering transcriptional events at the CD40 promoter.

PMID- 17507687
TI  - Functional analysis of maize RAD51 in meiosis and double-strand break repair.
AB  - In Saccharomyces cerevisiae, Rad51p plays a central role in homologous
      recombination and the repair of double-strand breaks (DSBs). Double mutants of
      the two Zea mays L. (maize) rad51 homologs are viable and develop well under
      normal conditions, but are male sterile and have substantially reduced seed set.
      Light microscopic analyses of male meiosis in these plants reveal reduced
      homologous pairing, synapsis of nonhomologous chromosomes, reduced bivalents at
      diakinesis, numerous chromosome breaks at anaphase I, and that >33% of quartets
      carry cells that either lack an organized nucleolus or have two nucleoli. This
      indicates that RAD51 is required for efficient chromosome pairing and its absence
      results in nonhomologous pairing and synapsis. These phenotypes differ from those
      of an Arabidopsis rad51 mutant that exhibits completely disrupted chromosome
      pairing and synapsis during meiosis. Unexpectedly, surviving female gametes
      produced by maize rad51 double mutants are euploid and exhibit near-normal rates
      of meiotic crossovers. The finding that maize rad51 double mutant embryos are
      extremely susceptible to radiation-induced DSBs demonstrates a conserved role for
      RAD51 in the repair of mitotic DSBs in plants, vertebrates, and yeast.

PMID- 17507689
TI  - Youth audience segmentation strategies for smoking-prevention mass media
      campaigns based on message appeal.
AB  - Mass media interventions are among the strategies recommended for youth cigarette
      smoking prevention, but little is known about optimal methods for reaching
      diverse youth audiences. Grades 4 through 12 samples of youth from four states (n
      = 1,230) rated smoking-prevention messages in classroom settings. Similar
      proportions of African American, Hispanic, and White youth participated. Impact
      of audience characteristics on message appeal ratings was assessed to provide
      guidance for audience segmentation strategies. Age had a strong effect on
      individual message appeal. The effect of gender also was significant. Message
      ratings were similar among the younger racial/ethnic groups, but differences were
      found for older African American youth. Lower academic achievement was associated
      with lower appeal scores for some messages. Age should be a primary consideration
      in developing and delivering smoking-prevention messages to youth audiences. The
      unique needs of boys and girls and older African American adolescents should also
      be considered.

PMID- 17507690
TI  - Characterization of an NBS1 C-terminal peptide that can inhibit ataxia
      telangiectasia mutated (ATM)-mediated DNA damage responses and enhance
      radiosensitivity.
AB  - ATM and NBS1, mutation of which lead to the human autosomal recessive diseases
      ataxia telangiectasia and Nijmegen breakage syndrome (NBS), respectively, are
      essential elements in the cellular response to DNA damage induced by ionizing
      radiation (IR). ATM is a member of the phosphatidylinositol 3-kinase family and
      is activated by IR in an NBS1-dependent manner. The extreme C terminus of NBS1
      contains an evolutionarily conserved sequence motif that is critical for binding
      to and activation of ATM after IR. ATM phosphorylates a series of targets to
      initiate cell cycle arrest and promote cell survival in response to DNA damage.
      Therefore, targeting the NBS1-ATM interaction may lead to a novel approach for
      specific ATM inhibition and radiosensitization. We developed small peptides
      containing the conserved C-terminal sequence of NBS1 to investigate whether these
      peptides can interfere with the DNA damage pathway. We found that wild-type NBS1
      inhibitory peptides (wtNIP) can abrogate NBS1-ATM association in the presence or
      absence of IR. We also found that cells exposed to wtNIP displayed a significant
      reduction in radiation-induced gamma-H2AX and NBS1 focus formation compared with
      cells treated with control peptides, demonstrating that wtNIP possesses a strong
      inhibitory effect on ATM. The inhibitory effect of wtNIP also leads to a
      significant decrease in clonogenic survival in response to IR. Furthermore, wtNIP
      does not radiosensitize cells with defective ATM, suggesting a specific
      inhibition of ATM. Together, these data provide a proof of principle for the use
      of NBS1 C-terminal small peptides as specific ATM inhibitors and
      radiosensitizers.

PMID- 17507691
TI  - Heparanase expression and function during early pregnancy in mice.
AB  - Embryo implantation is a complex process that involves interactions between cell
      surface and extracellular components of the blastocyst and the uterus, including
      blastocyst adhesion to the uterine luminal epithelium, epithelial basement
      membrane penetration and stromal extracellular matrix remodeling, angiogenesis,
      and decidualization. These processes all involve interactions with heparan
      sulfate (HS) proteoglycans, which harbor various growth factors and cytokines and
      support cell adhesion. Heparanase (HPSE) is an endo-beta-glucuronidase that
      cleaves HS at specific sites. HPSE also can act as an adhesion molecule
      independent of its catalytic activity. Thus, HPSE is a multifunctional molecule
      contributing to and modulating HS-dependent processes. Exogenously added HPSE
      improves embryo implantation in mice; however, no information is available
      regarding the normal pattern of HPSE expression and activity during the
      implantation process in any system. Using several approaches, including real-time
      RT-PCR, in situ hybridization, and immunohistochemistry, we determined that
      uterine HPSE expression increases dramatically during early pregnancy in mice.
      Heparanase mRNA and protein were primarily expressed in decidua and were rapidly
      induced at the implantation site. Uterine HPSE activity was characterized and
      demonstrated to increase >40-fold during early pregnancy. Finally, we demonstrate
      that the HPSE inhibitor PI-88 severely inhibits embryo implantation in vivo.
      Collectively, these results indicate that HPSE plays a role in blastocyst
      implantation and complements previous studies showing a role for HS-dependent
      interactions in this process.

PMID- 17507692
TI  - Induction of three vitellogenins by 17beta-estradiol with concurrent inhibition
      of the growth hormone-insulin-like growth factor 1 axis in a euryhaline teleost,
      the tilapia (Oreochromis mossambicus).
AB  - The objective of the present study was to utilize the male Mozambique tilapia
      (Oreochromis mossambicus) as a model for examining the molecular mechanisms that
      mediate the physiological transition between somatic and gonadal growth in female
      teleost fish, and in vertebrates in general. Partial cDNAs that encode multiple
      forms of vitellogenin (Vtg), which is the major precursor of yolk proteins, were
      cloned from estrogen-treated males and utilized to develop real-time quantitative
      RT-PCR assays, which were supplemented by an assay for Vtg immunoreactivity in
      the plasma. Alignment analyses of the amino acid sequences deduced from the vtg
      cDNAs revealed three distinct tilapia Vtgs, which were categorized as Aa-, Ab-,
      and C-type Vtgs. A single injection of male tilapias with 17beta-estradiol (E(2))
      at 5 microg/g body weight significantly increased the plasma E(2) and hepatic
      levels of all three vtg transcripts within 1 day. Plasma E(2) levels declined
      after 3 days, whereas the plasma Vtg immunoreactivity and hepatic levels of the
      three vtg transcripts continued to increase. Hepatic expression of the estrogen
      receptor (esr) 1 gene, but not the esr2 gene, also increased markedly 1 day after
      E(2) injection and remained elevated for 5 days. While plasma growth hormone (Gh)
      levels were unaffected, hepatic expression of transcripts that encoded the Gh
      receptor and insulin-like growth factor 1 (Igf1) was suppressed by E(2), as were
      the plasma Igf1 levels. These results clearly suggest a distinct negative
      interplay between the growth and reproductive axes at the molecular level of key
      hepatic regulatory pathways involved in the control of energy utilization by
      gonadal and somatic growth processes.

PMID- 17507693
TI  - Risk factors for recurrent diabetic foot ulcers: site matters.

PMID- 17507694
TI  - Metabolically healthy but obese women have an intermediate cardiovascular risk
      profile between healthy nonobese women and obese insulin-resistant women.

PMID- 17507695
TI  - Software for reading and grading diabetic retinopathy: Aravind Diabetic
      Retinopathy Screening 3.0.
AB  - OBJECTIVE: To evaluate the validity and reproducibility of software for reading
      digital images and grading diabetic retinopathy. RESEARCH DESIGN AND METHODS: A
      prospective, comparative observational study was conducted on a series of
      patients with type 2 diabetes who presented at the retina clinic of a tertiary
      care center in India. A total of 210 eyes of 105 patients were allocated to one
      of three ophthalmologists, who performed dilated indirect and direct
      ophthalmoscopy and subsequently assessed the digital images of the same group of
      patients who were masked to the patient's identity. The interobserver and
      intertest agreement between clinical assessments and grading of diabetic
      retinopathy using the software was estimated. RESULTS: Moderate nonproliferative
      diabetic retinopathy (NPDR) was most frequently diagnosed, both clinically and on
      evaluating digital images. The overall agreement between the clinical grading of
      diabetic retinopathy and the grading of images was 81.3% (kappa = 0.69, SE 0.04,
      P < 0.0001); there was good agreement (81.3%) for NPDR (kappa = 0.61, SE 0.05, P
      < 0.0001), but agreement was not as good (54.6%) for proliferative diabetic
      retinopathy (kappa = 0.29, SE 0.11, P = 0.005). Clinically significant macular
      edema was diagnosed in 33.3% (70 of 210) of eyes clinically and in 40.2% (84 of
      209) of eyes by grading images, and there was good agreement (89.5%) between the
      two (kappa = 0.77, SE 0.07, P < 0.0001). CONCLUSIONS: Aravind Diabetic
      Retinopathy Screening 3.0 is a simple and valid tool to assist in the detection
      of sight-threatening retinopathy and could supplement dilated fundus examinations
      by ophthalmologists on patients to detect diabetic retinopathy.

PMID- 17507696
TI  - Clinical factors associated with resistance to microvascular complications in
      diabetic patients of extreme disease duration: the 50-year medalist study.

PMID- 17507697
TI  - "Damm sokkor": factors associated with the quality of care of patients with
      diabetes: a study in primary care in Tunisia.
AB  - OBJECTIVE: To identify the organizational, physician, and patient factors
      associated with the quality of care of patients with diabetes in a low-/middle
      income country. RESEARCH DESIGN AND METHODS: Data from 2,160 randomly selected
      patients with diabetes were extracted from the manual medical records of a
      nationwide sample of 48 randomly selected health centers. Physician and
      organizational characteristics were collected from national reports,
      questionnaires, interviews, and observation at the centers. Univariate and
      multivariate regression analyses were undertaken to identify associations with
      four quality-of-care scores, based on processes and intermediate outcomes of care
      and 53 potential explanatory factors. RESULTS: The mean age of the study
      population was 62.4 years, mean duration of diabetes was 8.4 years, 62% were
      female, and 94% had type 2 diabetes. In the final multivariate models, factors
      independently and significantly associated with higher process-of-care scores
      were regional affluence, doctor motivation, and the use of chronic disease
      clinics (P < 0.05). Health centers with younger patients and increased
      availability of medication were independently and significantly associated with
      improved outcome-of-care scores (P < 0.05). The final models of the four quality
      of-care scores explained 55-71% of the variations in scores. CONCLUSIONS: Use of
      chronic disease clinics, availability of medication, and possibly doctor
      motivation appear to be the most strongly related modifiable factors influencing
      diabetes care. These findings will be used to develop and implement culturally
      appropriate quality improvement interventions to improve the quality of diabetes
      care. We recommend our findings be taken into account in other low-/middle-income
      countries.

PMID- 17507698
TI  - Images in clinical medicine. Eosinophilic esophagitis.

PMID- 17507699
TI  - New York to trans fats: you're out!

PMID- 17507700
TI  - Prohibiting genetic discrimination.

PMID- 17507701
TI  - The mixed promise of genetic medicine.

PMID- 17507702
TI  - Randomized comparison of strategies for reducing treatment in mild persistent
      asthma.
AB  - BACKGROUND: Treatment guidelines recommend the use of inhaled corticosteroids in
      patients with asthma who have persistent symptoms and the "stepping down" of
      therapy to the minimum needed to maintain control of asthma. Whether patients
      with asthma that is well controlled with the use of inhaled corticosteroids twice
      daily can receive a step-down treatment with once-daily montelukast (our primary
      hypothesis) or once-daily fluticasone propionate plus salmeterol (our secondary
      hypothesis) has not yet been determined. METHODS: We randomly assigned 500
      patients with asthma that was well controlled by inhaled fluticasone (100 microg
      twice daily) to receive continued fluticasone (100 microg twice daily) (169
      patients), montelukast (5 or 10 mg each night) (166 patients), or fluticasone
      (100 microg) plus salmeterol (50 microg) each night (165 patients). Treatment was
      administered for 16 weeks in a double-blind manner. The primary outcome was the
      time to treatment failure. RESULTS: Approximately 20% of patients assigned to
      receive continued fluticasone or switched to treatment with fluticasone plus
      salmeterol had treatment failure, as compared with 30.3% of subjects switched to
      montelukast. The hazard ratio for both comparisons was 1.6 (95% confidence
      interval, 1.1 to 2.6; P=0.03). The percentage of days on which patients were free
      of asthma symptoms (78.7 to 85.8%) was similar across the three groups.
      CONCLUSIONS: Patients with asthma that is well controlled with the use of twice
      daily inhaled fluticasone can be switched to once-daily fluticasone plus
      salmeterol without increased rates of treatment failure. A switch to montelukast
      results in an increased rate of treatment failure and decreased asthma control;
      however, patients taking montelukast remained free of symptoms on 78.7% of
      treatment days. (ClinicalTrials.gov number, NCT00156819 [ClinicalTrials.gov].).

PMID- 17507703
TI  - Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma.
AB  - BACKGROUND: Treatment guidelines recommend the regular use of inhaled
      corticosteroids for patients with mild persistent asthma. We investigated whether
      the symptom-driven use of a combination of beclomethasone dipropionate and
      albuterol (also known as salbutamol) in a single inhaler would be as effective as
      the regular use of inhaled beclomethasone and superior to the as-needed use of
      inhaled albuterol. METHODS: We conducted a 6-month, double-blind, double-dummy,
      randomized, parallel-group trial. After a 4-week run-in, patients with mild
      asthma were randomly assigned to receive one of four inhaled treatments: placebo
      twice daily plus 250 microg of beclomethasone and 100 microg of albuterol in a
      single inhaler as needed (as-needed combination therapy); placebo twice daily
      plus 100 microg of albuterol as needed (as-needed albuterol therapy); 250 microg
      of beclomethasone twice daily and 100 microg of albuterol as needed (regular
      beclomethasone therapy); or 250 microg of beclomethasone and 100 microg of
      albuterol in a single inhaler twice daily plus 100 microg of albuterol as needed
      (regular combination therapy). The primary outcome was the morning peak
      expiratory flow rate. RESULTS: In 455 patients with mild asthma who had a forced
      expiratory volume in 1 second of 2.96 liters (88.36% of the predicted value), the
      morning peak expiratory flow rate during the last 2 weeks of the 6-month
      treatment was higher (P=0.04) and the number of exacerbations during the 6-month
      treatment was lower (P=0.002) in the as-needed combination therapy group than in
      the as-needed albuterol therapy group, but the values in the as-needed
      combination therapy group were not significantly different from those in the
      groups receiving regular beclomethasone therapy or regular combination therapy.
      The cumulative dose of inhaled beclomethasone was lower in the as-needed
      combination therapy group than in the groups receiving regular beclomethasone
      therapy or regular combination therapy (P<0.001 for both comparisons).
      CONCLUSIONS: In patients with mild asthma, the symptom-driven use of inhaled
      beclomethasone (250 microg) and albuterol (100 microg) in a single inhaler is as
      effective as regular use of inhaled beclomethasone (250 microg twice daily) and
      is associated with a lower 6-month cumulative dose of the inhaled corticosteroid.
      (ClinicalTrials.gov number, NCT00382889 [ClinicalTrials.gov].).

PMID- 17507704
TI  - Glucose regulation in young adults with very low birth weight.
AB  - BACKGROUND: The association between small size at birth and impaired glucose
      regulation later in life is well established in persons born at term. Preterm
      birth with very low birth weight (<1500 g) is also associated with insulin
      resistance in childhood. If insulin resistance persists into adulthood, preterm
      birth with very low birth weight also may be associated with an increased risk of
      disease in adulthood. We assessed glucose tolerance and insulin sensitivity and
      measured serum lipid levels and blood pressure in young adults with very low
      birth weight. METHODS: We performed a standard 75-g oral glucose-tolerance test,
      measuring insulin and glucose concentrations at baseline and at 120 minutes in
      163 young adults (age range, 18 to 27 years) with very low birth weight and in
      169 subjects who had been born at term and were not small for gestational age.
      The two groups were similar with regard to age, sex, and birth hospital. We
      measured blood pressure and serum lipid levels, and in 150 very-low-birth-weight
      subjects and 136 subjects born at term, we also measured body composition by
      means of dual-energy x-ray absorptiometry. RESULTS: As compared with the subjects
      born at term, the very-low-birth-weight subjects had a 6.7% increase in the 2
      hour glucose concentration (95% confidence interval [CI], 0.8 to 12.9), a 16.7%
      increase in the fasting insulin concentration (95% CI, 4.6 to 30.2), a 40.0%
      increase in the 2-hour insulin concentration (95% CI, 17.5 to 66.8), an 18.9%
      increase in the insulin-resistance index determined by homeostatic model
      assessment (95% CI, 5.7 to 33.7), and an increase of 4.8 mm Hg in systolic blood
      pressure (95% CI, 2.1 to 7.4). Adjustment for the lower lean body mass in the
      very-low-birth-weight subjects did not attenuate these relationships.
      CONCLUSIONS: Young adults with a very low birth weight have higher indexes of
      insulin resistance and glucose intolerance and higher blood pressure than those
      born at term.

PMID- 17507705
TI  - Clinical practice. The syndrome of inappropriate antidiuresis.

PMID- 17507706
TI  - An HIV vaccine--evolving concepts.

PMID- 17507707
TI  - Images in clinical medicine. Azygous lobe.

PMID- 17507708
TI  - Case records of the Massachusetts General Hospital. Case 15-2007. A 20-year-old
      woman with asthma and cardiorespiratory arrest.

PMID- 17507709
TI  - Prematurity and the legacy of intrauterine stress.

PMID- 17507711
TI  - Clinical Decisions. Treatment of mild persistent asthma.

PMID- 17507712
TI  - Endoscopic versus surgical treatment for chronic pancreatitis.

PMID- 17507713
TI  - Air pollution and cardiovascular events.

PMID- 17507714
TI  - Inhaled insulin for diabetes mellitus.

PMID- 17507715
TI  - Assessment in medical education.

PMID- 17507716
TI  - Pulmonary-artery dissection in patients with Eisenmenger's syndrome.

PMID- 17507717
TI  - Monkeypox without exanthem.

PMID- 17507718
TI  - Colonic adenocarcinomas: near-infrared microcatheter imaging of smart probes for
      early detection--study in mice.
AB  - PURPOSE: To prospectively evaluate the ability of micro-fiberoptic catheters,
      which simultaneously record white light and near-infrared (NIR) images, to reveal
      colonic neoplasms after the intravenous administration of activatable "smart"
      probes that increase in NIR fluorescence subsequent to protease activation.
      MATERIALS AND METHODS: The institutional animal care committee approved all
      animal experiments. CT26 tumor cells were orthotopically implanted into the
      descending colon of C57BL6/J mice (n=10). Thirteen days later, mice intravenously
      received either 2 nmol of a protease-sensing probe that had cathepsin B as a
      major activator (n=5) or saline (control animals [n=5]). One day later, animals
      were noninvasively examined to the point of the splenic flexure by using
      microcatheter imaging. Excised colons were subsequently evaluated with
      epifluorescence imaging, histologic examination, and cathepsin B
      immunohistochemistry. Student t test was used for statistical analysis, with
      P<.05 considered to indicate a significant difference. RESULTS: Results with
      fiberoptic imaging demonstrated that all tumors were visible with the protease
      activatable probe, even when they were not readily apparent at white light
      imaging. A target-to-background ratio (TBR) of 8.86 for tumor to adjacent normal
      mucosa was achieved in the NIR channel after probe administration (P=.001),
      whereas white light images resulted in a TBR of 1.14 (P>.5) based on luminosity.
      The tumoral NIR fluorescence intensity was more than 30-fold greater in probe
      injected animals than in control animals, indicating that essentially all of the
      signal recorded in lesions was from activatable probe administration. Results of
      immunohistochemistry confirmed cathepsin B overexpression in the tumor compared
      with adjacent mucosa. CONCLUSION: The use of NIR imaging microcatheters combined
      with protease-activatable smart probes results in a beacon effect that highlights
      tumors with high TBRs; this technique thus may be a potentially useful adjunct to
      white light colonoscopy in the future.

PMID- 17507719
TI  - Prostate gland: MR imaging appearance after vascular targeted photodynamic
      therapy with palladium-bacteriopheophorbide.
AB  - PURPOSE: To prospectively evaluate the magnetic resonance (MR) imaging appearance
      of the prostate and periprostatic tissues after vascular targeted photodynamic
      therapy (VTP) with palladium-bacteriopheophorbide for locally recurrent carcinoma
      after external beam radiation therapy. MATERIALS AND METHODS: Informed consent
      was obtained from all patients, and approval was obtained from the ethics review
      boards of all participating institutions. Nonenhanced T2-weighted and dynamic
      gadolinium-enhanced T1-weighted MR imaging examinations were performed at
      baseline and 1 week, 4 weeks, and 6 months after VTP in 25 men (age range, 58-83
      years; mean age, 73 years) as part of a prospective phase I/II trial. Percentage
      of MR-depicted necrosis was defined as the volume of nonenhancing prostatic
      tissue 1 week after VTP divided by the volume of the prostate. Patterns of intra-
      and extraprostatic necrosis were recorded. Pearson correlation coefficients were
      used to test correlations between necrosis and prostate-specific antigen level.
      RESULTS: Contrast material-enhanced T1-weighted MR images obtained 1 week after
      therapy showed necrosis in all patients. Treatment margins were irregular in 21
      of 25 patients. T2-weighted images showed no clear treatment boundaries in any
      patient. Extraprostatic necrosis involved the puborectalis or levator ani muscles
      in 22, obturator internus muscle in 12, periprostatic veins in three, pubic bone
      marrow in four, and anterior rectal wall in nine of the 25 patients. The
      neurovascular bundle appeared to be spared in all patients. Percentage of MR
      depicted intraprostatic necrosis was correlated with percentage decrease in
      prostate-specific antigen level (from baseline) at 4 weeks (r=0.41, P=.04) and 12
      weeks (r=0.45, P=.02). CONCLUSION: Contrast-enhanced MR imaging depicts irregular
      margins of intraprostatic treatment effect. This finding suggests varied tissue
      sensitivities to VTP with palladium-bacteriopheophorbide.

PMID- 17507720
TI  - Breast MR imaging: computer-aided evaluation program for discriminating benign
      from malignant lesions.
AB  - PURPOSE: To retrospectively determine the sensitivity of kinetic features
      measured with computer-aided evaluation at breast magnetic resonance (MR) imaging
      in discriminating benign from malignant lesions, with histopathologic findings
      used as the reference standard. MATERIALS AND METHODS: Institutional review board
      approval was obtained for this HIPAA-compliant study. Informed consent was
      waived. Suspicious breast lesions visible only at MR imaging and in which biopsy
      had been performed with MR imaging guidance were retrospectively evaluated with a
      computer-aided evaluation program. Computer-generated kinetic features for each
      lesion were recorded, and those of benign and malignant lesions were compared.
      Features analyzed included the presence or absence of computer-aided evaluation
      "threshold enhancement" at 50% and 100% minimum thresholds; degree of initial
      peak enhancement; and enhancement profiles composed of lesion percentages of
      washout, plateau, and persistent enhancement. The Fisher exact test and Student t
      test were used to assess differences in these analyses. RESULTS: One hundred
      fifty-four consecutive lesions (41 malignant, 113 benign) in 125 women (age
      range, 27-86 years; mean age, 52 years) were evaluated. The presence of threshold
      enhancement at computer-aided evaluation was sensitive for malignancy, with 38 of
      41 (93%) malignant lesions demonstrating enhancement at both the 50% and 100%
      thresholds. Absence of threshold enhancement at computer-aided evaluation helped
      improve the discrimination between benign and malignant lesions when compared
      with that at initial interpretation by the radiologists. False-positive rates
      were reduced by 8.8% at the 50% enhancement threshold (not significant) and by
      23.0% at the 100% enhancement threshold (P=.02) when compared with that at
      initial interpretation. Analyses of initial peak enhancement values and
      enhancement profiles did not demonstrate further improvements in lesion
      discrimination. CONCLUSION: The use of computer-aided evaluation for breast MR
      imaging significantly helped improve the discrimination of benign from malignant
      lesions when compared with that at initial interpretations by radiologists.

PMID- 17507721
TI  - Internal carotid artery stenosis: accuracy of subjective visual impression for
      evaluation with digital subtraction angiography and contrast-enhanced MR
      angiography.
AB  - PURPOSE: To prospectively determine, for both digital subtraction angiography
      (DSA) and contrast material-enhanced magnetic resonance (MR) angiography, the
      accuracy of subjective visual impression (SVI) in the evaluation of internal
      carotid artery (ICA) stenosis, with objective caliper measurements serving as the
      reference standard. MATERIALS AND METHODS: Local ethics committee approval and
      written informed patient consent were obtained. A total of 142 symptomatic
      patients (41 women, 101 men; mean age, 70 years; age range, 44-89 years)
      suspected of having ICA stenosis on the basis of Doppler ultrasonographic
      findings underwent both DSA and contrast-enhanced MR angiography. With each
      modality, three independent neuroradiologists who were blinded to other test
      results first visually estimated and subsequently objectively measured stenoses.
      Diagnostic accuracy and percentage misclassification for correct categorization
      of 70%-99% stenosis were calculated for SVI, with objective measurements serving
      as the reference standard. Interobserver variability was determined with kappa
      statistics. RESULTS: After exclusion of arteries that were unsuitable for
      measurement, 180 vessels remained for analysis with DSA and 159 vessels remained
      for analysis with contrast-enhanced MR angiography. With respect to 70%-99%
      stenosis, SVI was associated with average misclassification of 8.9% for DSA
      (8.9%, 7.8%, and 10.0% for readers A, B, and C, respectively) and of 11.7% for
      contrast-enhanced MR angiography (11.3%, 8.8%, and 15.1% for readers A, B, and C,
      respectively). Negative predictive values were excellent (92.3%-100%).
      Interobserver variability was higher for SVI (DSA, kappa = 0.62-0.71; contrast
      enhanced MR angiography, kappa = 0.57-0.69) than for objective measurements (DSA,
      kappa = 0.75-0.80; contrast-enhanced MR angiography, kappa = 0.66-0.72).
      CONCLUSION: SVI alone is not recommended for evaluation of ICA stenosis with both
      DSA and contrast-enhanced MR angiography. SVI may be acceptable as an initial
      screening tool to exclude the presence of 70%-99% stenosis, but caliper
      measurements are warranted to confirm the presence of such stenosis.

PMID- 17507722
TI  - Screening mammography-detected cancers: sensitivity of a computer-aided detection
      system applied to full-field digital mammograms.
AB  - PURPOSE: To retrospectively evaluate the sensitivity of the performance of a
      computer-aided detection (CAD) system applied to full-field digital mammograms
      for detection of breast cancers in a screening group, with histologic findings as
      the reference standard. MATERIALS AND METHODS: This study had institutional
      review board approval, and patient informed consent was waived. A commercially
      available CAD system was applied to the digital mammograms of 103 women (mean
      age, 51 years; range, 35-69 years) with 103 breast cancers detected with
      screening. Sensitivity values of the CAD system according to mammographic
      appearance, breast composition, and histologic findings were analyzed. Normal
      mammograms from 100 women (mean age, 54 years; age range, 35-75 years) with no
      mammographic and clinical abnormality during 2-year follow-up were used to
      determine false-positive CAD system marks. Differences between the cancer
      detection rates in fatty and dense breasts for the CAD system were compared by
      using the chi(2) test. RESULTS: The CAD system correctly marked 99 (96.1%) of 103
      breast cancers. The CAD system marked all 44 breast cancers that manifested as
      microcalcifications only, all 23 breast cancers that manifested as a mass with
      microcalcifications, and 32 (89%) of 36 lesions that appeared as a mass only. The
      sensitivity of the CAD system in the fatty breast group was 95% (59 of 62) and in
      the dense breast group was 98% (40 of 41) (P = .537). The CAD system correctly
      marked all 31 lesions of ductal carcinoma in situ (DCIS), all 22 lesions of
      invasive ductal carcinoma with DCIS, the single invasive lobular carcinoma
      lesion, and 45 (92%) of 49 lesions of invasive ductal carcinoma. On normal
      mammograms, the mean number of false-positive marks per patient was 1.80 (range,
      0-10 marks; median, 1 mark). CONCLUSION: The CAD system can correctly mark most
      (96.1%) asymptomatic breast cancers detected with digital mammographic screening,
      with acceptable false-positive marks (1.80 per patient).

PMID- 17507723
TI  - Molecular imaging: the vision and opportunity for radiology in the future.
AB  - Molecular imaging is being hailed as the next great advance for imaging. This
      introductory article in the molecular imaging series to be published over the
      next several months in Radiology sets the stage for the subsequent set of
      articles by providing relevant definitions and background information and traces
      the evolution of molecular imaging to its current state of research and clinical
      practice. It discusses in detail the evolution of molecular imaging and the role
      that the National Cancer Institute and the National Institutes of Health have had
      in the funding and development of many of the important molecular imaging
      research programs that are in existence today. The article also provides basic
      information about the complex biology of the cell and details of the pathogenesis
      of cancer and how molecular imaging will be critical for earlier detection and
      management of cancer in the future. The article lays the foundation for the
      subsequent articles in the series and describes how and why molecular imaging
      will be critical and integral for clinical care of patients in the future. The
      introductory article also discusses the relevance of molecular imaging to
      clinical radiology practice and why it is critical for the practicing radiologist
      to understand these evolving techniques, as they will be the future of imaging.

PMID- 17507724
TI  - Polyp measurement reliability, accuracy, and discrepancy: optical colonoscopy
      versus CT colonography with pig colonic specimens.
AB  - PURPOSE: To prospectively evaluate the reliability and accuracy of optical
      colonoscopy and computed tomographic (CT) colonography in polyp measurement, by
      using direct measurement as the reference standard, and to understand the basis
      for measurement discrepancy between both modalities. MATERIALS AND METHODS:
      Eighty-six simulated polyps that ranged from 3 to 15 mm were constructed by using
      pig colons obtained from an abattoir. Approval of the animal care and use
      committee for the study was not required. CT colonographic measurement was
      performed by two independent radiologists by using two-dimensional (2D) optimized
      multiplanar reformatted planes and three-dimensional (3D) endoluminal views.
      Optical colonoscopic measurement was performed by two independent
      gastroenterologists by using open biopsy forceps. Interobserver agreement,
      measurement error, measurement discrepancy defined as the result of subtracting
      the optical colonoscopic measurement from the CT colonographic measurement, and
      false-mismatch (ie, designation of matched polyps as mismatched between both
      modalities) rates according to different matching criteria were analyzed.
      RESULTS: Intraclass correlation coefficients were 0.879 (95% confidence interval:
      0.780, 0.930) for optical colonoscopy, 0.979 (95% confidence interval: 0.956,
      0.989) for 2D CT colonography, and 0.985 (95% confidence interval: 0.976, 0.990)
      for 3D CT colonography. The mean standardized polyp size +/- standard deviation
      for each observer was 76.3% +/- 14.7 and 85.3% +/- 18.8 for optical colonoscopy,
      104.6% +/- 11.6 and 101.6% +/- 10.1 for 2D CT colonography, and 114% +/- 12.4 and
      113.4% +/- 13.2 for 3D CT colonography. These values indicated that there was a
      statistically significant difference among the methods (P<.001). Measurement
      discrepancy was not proportional to polyp size. A percentage-of-error criterion
      showed increasing false-mismatch rates with decreasing polyp size, whereas a
      fixed margin-of-error criterion resulted in more uniform false-mismatch rates
      across polyp size. CONCLUSION: CT colonography is more reliable and accurate than
      optical colonoscopy for polyp measurement. A fixed margin-of-error criterion is
      better than a percentage-of-error criterion for polyp matching between CT
      colonography and optical colonoscopy with open biopsy forceps.

PMID- 17507725
TI  - Blueprint for imaging in biomedical research.

PMID- 17507726
TI  - Bone deficit and bone health.

PMID- 17507727
TI  - Patient assessment in the diagnosis, prevention, and treatment of osteoporosis.
AB  - Assessment of the patient with osteoporosis includes history and physical
      examination, laboratory testing, and imaging studies. Information gathered during
      this assessment assists clinicians in targeting strategies to prevent fractures.
      The medical history should contain items such as personal and family history of
      fractures, lifestyle, intake of substances such as vitamin D, calcium,
      corticosteroids, and other medications. The physical examination can reveal
      relevant information such as height loss and risk of falls. Bone mineral density
      (BMD), most commonly determined by dual-energy x-ray absorptiometry, best
      predicts fracture risk in patients without previous fracture. BMD testing is most
      efficient in women over 65 years old but is also helpful for men and women with
      risk factors. Serial BMD tests can identify individuals losing bone mass, but
      clinicians should be aware of what constitutes a significant change. Laboratory
      testing can detect other risk factors and can provide clues to etiology.
      Selection of laboratory tests should be individualized, as there is no consensus
      regarding which tests are optimal. Biochemical markers of bone turnover have a
      potential role in fracture risk assessment and in gauging response to therapy,
      but are not widely used at present. Clinicians should be aware of problems with
      vitamin D measurement, including seasonal variation, variability among
      laboratories, and the desirable therapeutic range. Careful assessment of the
      osteoporotic patient is essential in developing a comprehensive plan that reduces
      fracture risk and improves quality of life.

PMID- 17507728
TI  - Review of postmenopausal osteoporosis pharmacotherapy.
AB  - The degradation of bone tissue leading to osteoporosis is often silent and
      unrecognized until a postmenopausal woman develops a bone fracture. The costs of
      medical treatment and subsequent changes in the quality of life of a patient are
      significant, and avoidance via proper nutrition, exercise, and pharmacologic
      therapy may be the key to decreasing healthcare costs associated with this
      disease state. A periodic review of current literature is necessary to update the
      reader of current therapeutic options for the treatment and prevention of
      osteoporosis. A number of medications exist, and new options are ongoing.
      Clinicians now have access to antiresorptive and anabolic therapy in addition to
      lifestyle modification as options for patients. This article consists of a review
      of established guidelines for screening, diagnosis, and pharmacologic modalities
      and will provide a comprehensive assessment of therapeutic options.

PMID- 17507729
TI  - Calcium supplementation in clinical practice: a review of forms, doses, and
      indications.
AB  - Most Americans do not meet the adequate intake (AI) for calcium; calcium
      supplements can help meet requirements. Calcium supplementation has been found to
      be beneficial for bone health in children, young adults, and menopausal women. In
      addition to calcium, vitamin D is necessary for bone health and is generally
      deficient in the industrialized world. Calcium from carbonate and citrate are the
      most common forms of calcium supplements. Calcium carbonate, the most cost
      effective form, should be taken with a meal to ensure optimal absorption. Calcium
      citrate can be taken without food and is the supplement of choice for individuals
      with achlorhydria or who are taking histamine-2 blockers or protein-pump
      inhibitors. Calcium lactate and calcium gluconate are less concentrated forms of
      calcium and are not practical oral supplements. Research on hydroxyapatite as a
      source of calcium is limited, so this form of calcium is not recommended. The
      maximum dose of elemental calcium that should be taken at a time is 500 mg. U.S.
      Pharmacopeia-verified calcium supplements meet vigorous manufacturing and quality
      requirements. Absorption from calcium-fortified beverages varies and in general
      is not equal to that of milk. Potential adverse effects of calcium
      supplementation include gastrointestinal complaints. Renal calculi in most
      studies have not been associated with calcium supplementation. The risk of
      advanced and fatal prostate cancer has been associated with calcium intakes from
      food or supplements in amounts >1500 mg/d.

PMID- 17507731
TI  - Vitamin d and its role in cancer and immunity: a prescription for sunlight.
AB  - Vitamin D has been recognized for more than a century as essential for the normal
      development and mineralization of a healthy skeleton. More extensive roles for
      vitamin D were suggested by the discovery of the vitamin D receptor (VDR) in
      tissues that are not involved in calcium and phosphate metabolism. VDR has been
      discovered in most tissues and cells in the body and is able to elicit a wide
      variety of biologic responses. These observations have been the impetus for a
      reevaluation of the physiologic and pharmacologic actions of vitamin D. Here, we
      review the role of vitamin D in regulation of the immune system and its possible
      role in the prevention and treatment of cancer and immune-mediated diseases.

PMID- 17507730
TI  - Vitamin d and rehabilitation: improving functional outcomes.
AB  - Vitamin D inadequacy is pandemic among rehabilitation patients in both inpatient
      and outpatient settings. Male and female patients of all ages and ethnic
      backgrounds are affected. Vitamin D deficiency causes osteopenia, precipitates
      and exacerbates osteoporosis, causes the painful bone disease osteomalacia, and
      worsens proximal muscle strength and postural sway. Vitamin D inadequacy can be
      prevented by sensible sun exposure and adequate dietary intake with
      supplementation. Vitamin D status is determined by measurement of serum 25
      hydroxyvitamin D. The recommended healthful serum level is between 30 and 60
      ng/mL. 25-Hydroxyvitamin D levels of >30 ng/mL are sufficient to suppress
      parathyroid hormone production and to maximize the efficiency of dietary calcium
      absorption from the small intestine. This can be accomplished by ingesting 1000
      IU of vitamin D(3) per day, or by taking 50,000 IU of vitamin D(2) every 2 weeks.
      Vitamin D toxicity is observed when 25-hydroxyvitamin D levels exceed 150 ng/mL.
      Identification and treatment of vitamin D deficiency reduces the risk of
      vertebral and nonvertebral fractures by improving bone health and musculoskeletal
      function. Vitamin D deficiency and osteomalacia should be considered in the
      differential diagnosis of patients with musculoskeletal pain, fibromyalgia,
      chronic fatigue syndrome, or myositis. There is a need for better education of
      health professionals and the general public regarding the optimization of vitamin
      D status in the care of rehabilitation patients.

PMID- 17507732
TI  - Low serum total calcium concentration as a marker of low serum ionized calcium
      concentration in critically ill patients receiving specialized nutrition support.
AB  - BACKGROUND: The intent of this study was to ascertain to what extent serum total
      calcium concentration (tCa) <7 mg/dL reflects hypocalcemia (defined by ionized
      calcium concentration [iCa] of < or = 1.12 mmol/L) in critically ill patients
      receiving specialized nutrition support. METHODS: Adult patients (> or = 18
      years) admitted to the trauma, surgical, medical, burn, or neurosurgical
      intensive care units, trauma stepdown unit, or progressive care unit and referred
      to the nutrition support service were retrospectively identified for potential
      inclusion into the study. Serum chemistries, arterial blood gas measurements,
      nutrition markers, and serum iCa were simultaneously obtained from each patient
      approximately 1 day after initiation of specialized nutrition support. Patients
      with a serum creatinine > or = 2 mg/dL, hyperphosphatemia (> or = 6 mg/dL),
      severe hypomagnesemia (< or = 1.12 mg/dL), history of metabolic bone disease, or
      parathyroid disease were excluded from the analysis. RESULTS: One hundred ninety
      five patients (91% who had multiple trauma, with a mean Injury Severity Score 31
      +/- 13) were enrolled into the study. Specialized nutrition support was initiated
      2.8 +/- 1.8 days and calcium status was studied 4.2 +/- 3.1 days after hospital
      admission, respectively. The majority (28 of 33, or 85%) of patients with a tCa
      <7 mg/dL were hypocalcemic compared with 33% (22 out of 66) of patients with a
      tCa of 7-7.4 mg/dL, and 11% (11 of 96) of those with a tCa of 7.5-7.9 mg/dL (p <
      .001). CONCLUSIONS: Critically ill patients with a serum total calcium
      concentration of <7 mg/dL have a high rate of hypocalcemia (iCa < or = 1.12
      mmol/L). Hypocalcemia, defined as a serum iCa of < or = 1.12 mmol/L, occurs in
      85% of acutely ill patients with a serum tCa <7 mg/dL.

PMID- 17507733
TI  - A review of the relationship between parenteral nutrition and metabolic bone
      disease.
AB  - Metabolic bone disease (MBD) refers to the conditions that produce a diffuse
      decrease in bone density and strength because of an imbalance between bone
      resorption and bone formation. MBD can be a potential complication in patients
      receiving chronic parenteral nutrition (PN) therapy and the management of this
      condition presents a challenge for many clinicians. The etiology of PN-associated
      MBD is poorly understood, but traditional risk factors can include malnutrition,
      vitamin and mineral deficiencies, toxic contaminants in the PN solution,
      concomitant medications, and presence of certain disease states. Although
      additional studies are warranted to further elucidate the development and
      management of this condition, the following review discusses some of the
      important factors that may play a role in the genesis of PN-associated MBD and
      evaluates some potential strategies for the diagnosis and treatment of this
      complication.

PMID- 17507734
TI  - Principles and strategies for monitoring home parenteral nutrition.
AB  - Patients who cannot ingest adequate calories to maintain body weight via their
      gastrointestinal tract may require parenteral nutrition (PN) at home. As with any
      therapy, the patient must be evaluated to determine if the home PN (HPN) is
      effective and the patient is free of complications. This review discusses
      specific items to monitor for HPN patients. Parameters to monitor can be divided
      into those used to determine effectiveness and those used to prevent
      complications of HPN. In addition, potential HPN-associated complications can be
      divided into those that occur with short- or long-term PN administration.
      Specific items to monitor are discussed within this framework.

PMID- 17507735
TI  - Use of probiotics in pediatrics: rationale, mechanisms of action, and practical
      aspects.
AB  - The use of probiotics (ingested microbes that can modify intestinal microbial
      populations in a way that benefit the host) has moved from concept to actual
      demonstration of specific benefits by specific microorganisms for specific
      populations. It is increasingly clear that these benefits to the host are mostly
      mediated by the profound effect that intestinal microflora (microbiota) have on
      gut barrier function and host immune response. Intestinal bacteria are more
      numerous than the human cells of the host that harbors them. Despite having many
      potential pathogens in this microflora, humans do not routinely get infected. It
      is no coincidence that gut-associated immune tissue constitutes approximately 80%
      of all immunologically active cells in the human host. The gut interacts with
      intestinal bacteria, both resident and ingested, to develop protective mechanisms
      (via improving gut barrier function and immune stimulation for defense) and
      appropriate, nonexaggerated responses (via immune modulation and immune
      tolerance) to support host health. The mechanisms of this interaction between
      host and bacteria are increasingly being unraveled and in great part explain the
      clinical benefits that have been reported with specific probiotic bacteria by
      enhancing host defense mechanisms (such as for treatment and prevention of viral
      diarrhea and reducing risk of necrotizing enterocolitis), mitigating antibiotic
      associated diarrhea, and modulating host immune response (such as in allergic
      disease).

PMID- 17507736
TI  - Safety and stability of lipid emulsions.

PMID- 17507738
TI  - The impact of varying dietary protein on serum IGF-I, IGFBP-1, and IGFBP-3 during
      6 days of physical activity.
AB  - This study was designed to investigate the impact of dietary protein intake on
      serum concentrations of IGF-I and IGFBP-1 and relative amounts of serum IGFBP-3
      during 6 d of physical activity. Ten men (23.8 +/- 2.0 y of age) were assigned to
      1 of 3 trials in a random crossover design. Each trial was isocaloric but with
      varying amounts of dietary protein: 50 g, 100 g, or 200 g. Subjects expended 500
      kcal through treadmill running or weightlifting on alternate days for 6 d.
      Fasting blood samples were obtained for measurement of IGF-I, IGFBP-1, and IGFBP
      3. Pre-post 24-h urine was measured for urea nitrogen. 50 g/d of protein resulted
      in a negative nitrogen balance, whereas 100 g/d and 200 g/d resulted in a
      positive nitrogen balance--200 g greater (P < 0.05) than 50 g and 100 g. Baseline
      IGF-I, BP-1, and BP-3 were not different among treatments. IGF-I decreased (P =
      0.002) during the 6 d. Postintervention IGFBP-I was greater (P = 0.03) than at
      baseline. Postintervention IGFBP-3 values were not different from baseline or
      between trials. A 6-d modification of protein intake, while in energy balance,
      during a strength and conditioning program does not appear to modify serum
      concentrations of IGF-I or IGFBP-1 or relative amounts of IGFBP-3.

PMID- 17507739
TI  - Preexercise carbohydrate consumption and repeated anaerobic performance in pre-
      and early-pubertal boys.
AB  - This study examined the effect of preexercise carbohydrate (CHO) feeding on
      performance on a Wingate anaerobic test (WAnT) in 11 boys (10.2 +/- 1.3 y old).
      Four WAnTs with 2 min recovery were performed 30 min after consuming a CHO (1 g
      CHO/kg) or placebo drink. Peak power (PP) and mean power (MP) were similar
      between trials. PP ranged from 241.1 +/- 82.2 to 223.1 +/- 57.9 W with
      carbohydrate and from 238.2 +/- 76.1 to 223.4 +/- 52.3 W with placebo. MP ranged
      from 176.3 +/- 58.4 to 151.1 +/- 37.5 W with carbohydrate versus 178.0 +/- 45.8
      to 159.1 +/- 32.7 W with placebo. Preexercise glucose was significantly higher in
      CHO versus placebo (7.0 +/- 1.0 vs. 5.5 +/- 0.5 mmol/L), but postexercise values
      were not different. Blood lactate was similar between trials but increased over
      time. This study found that the ingestion of a CHO solution before exercise did
      not influence power output during repeated performances of the WAnT.

PMID- 17507740
TI  - Cardiovascular fitness and vascular inflammatory markers after acute aerobic
      exercise.
AB  - Inflammatory markers such as C-reactive protein (CRP), fibrinogen, and white
      blood-cell (WBC) count are strongly associated with cardiovascular disease. The
      authors' purpose was to compare the inflammatory response to a single aerobic
      exercise session between individuals of high and moderate fitness. Ten apparently
      healthy highly fit and 11 moderately fit men expended 500 kcal at 70% of VO2peak.
      Fasting blood samples were obtained on 2 consecutive days before and again at 24,
      72, and 120 h postexercise. Blood samples were analyzed for CRP, fibrinogen, and
      WBC count. CRP was 76% lower at baseline in the highly fit group than in the
      moderately fit group (P = 0.03). CRP, fibrinogen, and WBC count remained
      unaltered, however, in the days after exercise (P > 0.05 for all). These findings
      suggest that markers of inflammation are stable in the days after a single
      session of moderate-intensity aerobic exercise in apparently healthy men of at
      least average fitness.

PMID- 17507741
TI  - Hydration during exercise in warm, humid conditions: effect of a caffeinated
      sports drink.
AB  - Caffeine is regarded as a diuretic despite evidence that hydration is not
      impaired with habitual ingestion. The purpose of this study was to determine
      whether a caffeinated sports drink impairs fluid delivery and hydration during
      exercise in warm, humid conditions (28.5 degrees C, 60% relative humidity).
      Sixteen cyclists completed 3 trials: placebo (P), carbohydrate-electrolyte (CE),
      and caffeinated (195 mg/L) sports drink (CAF+CE). Subjects cycled for 120 min at
      60-75%VO2max followed by 15 min of maximal-effort cycling. Heart rate and rectal
      temperature were similar until the final 15 min, when these responses and
      exercise intensity were higher with CAF+CE than with CE and P. Sweat rate, urine
      output, plasma- volume losses, serum electrolytes, and blood deuterium-oxide
      accumulation were not different. Serum osmolality was higher with CAF+CE vs. P
      but not CE. The authors conclude that CAF+CE appears as rapidly in blood as CE
      and maintains hydration and sustains cardiovascular and thermoregulatory function
      as well as CE during exercise in a warm, humid environment.

PMID- 17507742
TI  - Estimated energy expenditure and physical activity patterns of adolescent
      distance runners.
AB  - The purpose of this study was to examine the estimated total energy expenditure
      (TEE) and physical activity patterns of adolescent distance runners. Twenty-eight
      (20 male, 8 female) adolescent distance runners self-reported their daily
      physical activity with the Bouchard 3-d diary. Mean values for TEE, 57.4 +/- 11.6
      and 51.0 +/- 9.8 kcal x kg(-1) x d(-1), and activity energy expenditure (AEE),
      26.7 +/- 10.4 and 21.0 +/- 8.8 kcal x kg(-1) x d(-1), when expressed per kilogram
      body mass were not significantly different between males and females,
      respectively (P = 0.18). When expressed in absolute terms, TEE, 3609 +/- 927 and
      2467 +/- 426 kcal/d, and AEE, 1688 +/- 746 and 977 +/- 269 kcal/d, were
      significantly higher in males than in females, respectively. The results document
      the energy expenditure and self-reported physical activity of adolescent distance
      runners and might be used to address recommendations for adequate dietary energy
      requirements in this group, which in turn is important for energy balance in the
      context of normal growth, health, and physical performance.

PMID- 17507743
TI  - Carbohydrate loading and female endurance athletes: effect of menstrual-cycle
      phase.
AB  - This study compared 3 d of carbohydrate loading (CHOL; 8.4 g x kg(-1) x d(-1)
      carbohydrate) in female eumenorrheic athletes with 3 d of an isoenergetic normal
      diet (NORM; 5.2 g x kg(-1) x d(-1) carbohydrate) and examined the effect of
      menstrual-cycle phase on performance, muscle-glycogen concentration [glyc], and
      substrate utilization. Nine moderately trained eumenorrheic women cycled in an
      intermittent protocol varying in intensity from 45% to 75% VO2max for 75 min,
      followed by a 16-km time trial at the midfollicular (MF) and midluteal (ML)
      phases of the menstrual cycle on NORM and CHOL. Time-trial performance was not
      affected by diet (CHOL 26.10 +/- 1.04 min, NORM 26.16 +/- 1.35 min; P = 0.494) or
      menstrual-cycle phase (MF 26.05 +/- 1.10 min, ML 26.23 +/- 1.33 min; P = 0.370).
      Resting [glyc] was lowest in the MF phase after NORM (575 +/- 145 mmol x kg(-1) x
      dw(-1)), compared with the MF phase after CHOL (728 mmol x kg(-1) x dw(-1)) and
      the ML phase after CHOL and NORM (756 and 771 mmol x kg(-1) x dw(-1),
      respectively). No effect of phase on substrate utilization during exercise was
      observed. These data support previous observations of greater resting [glyc] in
      the ML than the MF phase of the menstrual cycle and suggest that lower glycogen
      storage in the MF phase can be overcome by carbohydrate loading.

PMID- 17507744
TI  - Does sodium-bicarbonate ingestion improve simulated judo performance?
AB  - The aim of the present study was to investigate whether preexercise sodium
      bicarbonate ingestion improves judo-related performance. The study used 2
      different protocols to evaluate performance: 3 bouts of a specific judo test (n =
      9) and 4 bouts of the Wingate test for upper limbs (n = 14). In both protocols
      athletes ingested 0.3 g/kg of sodium bicarbonate or placebo 2 h before the tests.
      Blood samples were collected to determine lactate level, and levels of perceived
      exertion were measured throughout the trials. The study used a double-blind,
      counterbalanced, crossover design. Ingestion of sodium bicarbonate improved
      performance in Bouts 2 and 3 of Protocol 1 (P < 0.05), mean power in Bouts 3 and
      4 of Protocol 2 (P < 0.05), and peak power in Bout 4 of Protocol 2 (P < 0.05).
      Ingestion of bicarbonate increased lactate concentration in Protocol 1 (P < 0.05)
      but not in Protocol 2. Ratings of perceived exertion did not differ between
      treatments. In conclusion, sodium bicarbonate improves judo-related performance
      and increases blood lactate concentration but has no effect on perceived
      exertion.

PMID- 17507745
TI  - Pseudoatoms and preferred skeletons in crystals.
AB  - The generalization of the Zintl-Klemm concept provides a universal formulation of
      a crystal structure in terms of universal building skeletons formed by Klemm's
      pseudoatoms: atoms that behave structurally according to their formal total
      electron charge. An important difference in this novel view is that charge is
      considered to be transferred, in the strict Zintl's sense, from the donor cations
      to the building skeleton as a whole, not specifically to a given atom or ion.
      Although application is restricted to (IV)-(IV) compounds (group 14 structures),
      the principle seems to be universal and can be applied to understand, to relate
      and to predict the structure of complex compounds on the basis of more simple
      structures, e.g. a given AB skeleton provides the building block for A(2)B,
      AB(2), ABX(m) etc. compounds of a very different nature. The application of such
      a principle only requires information on the constituent atoms and on the
      existing phases of the p-block elements (observed under ambient and high-pressure
      and/or high-temperature conditions). The ideas introduced here demonstrate, for
      the first time, that a generalization of the Zintl-Klemm concept is possible and
      that such a generalization helps to establish a univocal link between chemical
      composition (in terms of pseudoatoms) and the crystalline structures observed
      experimentally.

PMID- 17507746
TI  - Structures of stable and metastable Ge2Bi2Te5, an intermetallic compound in a
      GeTe-Bi2Te3 pseudobinary system.
AB  - Ge(2)Bi(2)Te(5) in the GeTe-Bi(2)Te(3) pseudobinary system has two single
      crystalline phases: a metastable phase with an NaCl-type structure and a stable
      phase with a nine-layer trigonal structure. In the metastable phase, the
      structure consists, in the hexagonal notation, of infinitely alternating stacks
      of Te and Ge/Bi layers at equal intervals along the c axis. On the other hand, in
      the stable phase those two layers are stacked alternately nine times to form an
      NaCl block. The blocks are then piled to construct a nine-layered trigonal
      structure with cubic close-packed stacking. Both ends of each block are covered
      with Te layers, contrary to the infinite alternation of Ge/Bi and Te layers in
      the structure of the metastable phase. The Ge/Bi layers in the metastable phase
      contain as much as 20 at. % vacancies; on the other hand, those in the stable
      phase are filled with atoms. These two crystalline phases in Ge(2)Bi(2)Te(5) have
      identical atomic configurations to the two corresponding phases found in
      Ge(2)Sb(2)Te(5).

PMID- 17507747
TI  - Crystal chemistry of borates: the classification and algebraic description by
      topological type of fundamental building blocks.
AB  - The structural characteristics of all the borates available were analyzed using
      the Inorganic Crystal Structure Database. The fundamental building blocks (FBBs)
      in 841 borates were systematically classified into 6 types in terms of their
      topological structures. By including the polymerization of the FBBs in the borate
      structure, a novel systematic classification and an algebraic description of
      borates have been proposed. The current systematic borate classification, in
      which all the identical FBBs can be classified into the same type, is more
      reasonable and provides new insight into the structural differences between
      various borates. The current, simpler, algebraic description is more extensive
      and can reflect more of the structural information of borates. This thus provides
      an impetus for elucidating the topological features of borates. Our work also
      provides much useful information on the design and search for novel borates,
      which is also helpful to classify newly synthesized borates and to strengthen the
      understanding of the overall scope of borate structures.

PMID- 17507748
TI  - On the polyhedral volume ratios V A/V B in perovskites ABX3.
AB  - This paper presents analytical expressions for the calculation of ratios of
      cation coordination polyhedra volumes (V(A)/V(B)) for perovskites ABX(3) of the
      Stokes-Howard diagram directly from atomic coordinates. We show the advantages of
      quantifying perovskite structure distortion with polyhedral volume ratios rather
      than with tilting angles, and discuss why space groups with multiple
      crystallographically inequivalent A or B sites (I4/mmm, Immm, P4(2)/nmc etc.) are
      much less common than those with a single A and B site (I4/mcm, R?bar 3c, Pnma
      etc.). Analysis of crystallographic data for approximately 1300 perovskite
      structures of oxides, halides and chalcogenides from the Inorganic Crystal
      Structure Database revealed that the most highly distorted perovskites belong to
      the space group Pnma and formally lower-symmetry perovskites (I2/m, I2/a) are
      less distorted geometrically. Critical values of the V(A)/V(B) ratios for the
      most common phase transitions Pnma <--> I4/mcm and Pnma<--> R?bar 3c are
      estimated to be approximately 4.85 with the possible intermediate space group
      Imma stable in the very narrow range of V(A)/V(B) approximately 4.8-4.9.
      Transitions to post-perovskite CaIrO(3)-type structures may be expected for
      V(A)/V(B) < 3.8.

PMID- 17507749
TI  - Superspace crystal symmetry of thermoelectric misfit cobalt oxides and predicted
      structural models.
AB  - Single crystals of thermoelectric misfit lamellar cobalt oxide phases in the Bi
      Ca-Co-O and I-Bi-Ca-Co-O systems were synthesized. They are characterized by
      aperiodic structures involving two partially independent sublattices: a CdI(2)
      type pseudohexagonal CoO(2) layer and a rocksalt-type BiCaO(2) slab allowing the
      intercalation of iodine. The crystal symmetry of these structures is discussed
      using the four-dimensional superspace formalism. The superspace Laue classes of
      the iodine-free and the intercalated compounds are P2/m(0delta(1/2)) (a(1) =
      4.901, b(1) = 4.730, b(2) = 2.80, c(1) = 14.66 A, beta = 93.49 degrees ) and
      A2/m(0delta1) (a'1 = 4.903, b'1 = 4.742, c'1 = 36.51 A, beta = 87.30 degrees ),
      respectively. A comparison is given with the related Bi-Sr-Co-O misfit compounds.
      The present structures are compatible with the presence of an intrinsic
      modulation with a wavelength matching the misfit aperiodicity in the b direction.
      Preliminary partial structure refinements confirm the layer stacking of the
      structure and the intercalation of I between the Bi-O layers for the second
      phase. A comparison with other cobalt oxide phases, as well as symmetry and
      metric considerations allow us to predict average structures for these new phases
      and to describe the common structural features assumed for all these lamellar
      misfit cobalt oxides.

PMID- 17507750
TI  - In situ observation of the tetragonal-cubic phase transition in the CeZrO4 solid
      solution--a high-temperature neutron diffraction study.
AB  - The crystal structure of the compositionally homogeneous ceria-zirconia solid
      solution CeZrO(4) is refined by Rietveld analysis of neutron diffraction data
      measured in situ over the temperature range 296-1831 K. The CeZrO(4) exhibits a
      tetragonal structure with the space group P4(2)/nmc at temperatures from 296 to
      1542 K (Z = 1), and a cubic fluorite-type form with the space group Fm?overline 3
      m at 1831 K (Z = 2). The isotropic atomic displacement parameters of Ce and Zr
      atoms B(Ce,Zr) and O atoms B(O) are found to increase with temperature, with B(O)
      being larger than B(Ce,Zr), suggesting the higher diffusivity of oxygen ions. The
      ratio of the c axial length to the a length of the pseudo-fluorite lattice
      (c/a(F) axial ratio) for the tetragonal CeZrO(4) phase increased from 296 to 1034
      K and decreased from 1291 to 1542 K, reaching unity between 1542 and 1831 K. The
      displacement of O atoms along the c axis in the tetragonal CeZrO(4) phase
      increased from 296 to 1034 K and decreased from 1291 to 1542 K, reaching 0.0 A
      between 1542 and 1831 K. These results indicate that the cubic-to-tetragonal
      phase transition between 1542 and 1831 K is accompanied by oxygen displacement
      along the c axis and the increase of the c/a(F) axial ratio from unity.

PMID- 17507751
TI  - Electron diffraction and microscopy study of the structure and microstructure of
      the hexagonal perovskite Ba3Ti2MnO9.
AB  - This paper reports a structural and microstructural investigation of the
      hexagonal perovskite Ba(3)Ti(2)MnO(9) using electron microscopy and diffraction.
      Convergent-beam electron diffraction (CBED) revealed the structure has the non
      centrosymmetric space group P6(3)mc (186) at room temperature and at
      approximately 110 K. Compared with the centrosymmetric parent structure BaTiO(3),
      with space group P6(3)/mmc, this represents a break in mirror symmetry normal to
      the c axis. This implies the Ti and Mn atoms are ordered on alternate octahedral
      sites along the 0001 direction in Ba(3)Ti(2)MnO(9). Using high-resolution
      electron microscopy (HREM), we observed occasional 6H/12R interfaces on (0001)
      planes, however, no antiphase boundaries were observed, as were seen in
      Ba(3)Ti(2)RuO(9). Using powder X-ray Rietveld refinement we have measured the
      lattice parameters from polycrystalline samples to be a = 5.6880 +/- 0.0005, c =
      13.9223 +/- 0.0015 A at room temperature.

PMID- 17507752
TI  - LiNaSiB3O7(OH)--novel structure of the new borosilicate mineral jadarite
      determined from laboratory powder diffraction data.
AB  - The structure of a new mineral jadarite, LiNaSiB(3)O(7)(OH) (IMA mineral 2006
      36), has been determined by simulated annealing and Rietveld refinement of
      laboratory X-ray powder diffraction data. The structure contains a layer of
      corner-sharing, tetrahedrally coordinated Li, Si and B forming an unbranched
      vierer single layer, which is decorated with triangular BO(3) groups. The Na ion
      is situated between the tetrahedral layers in a distorted octahedral site. As the
      very high boron content in this mineral makes obtaining neutron diffraction data
      very problematic, ab initio optimization using VASP was used to validate the
      structure and to better localize the H atom. The H atom is located on the apex of
      the triangular BO(3) group and is involved in a weak intralayer hydrogen bond.
      The final Rietveld refinement agrees with the ab initio optimization with regard
      to a hydrogen bond between the H atom and one of the tetrahedral corner O atoms.
      The refined structure seems to be of a remarkably high quality given the
      complexity of the structure, the high proportion of very light elements and the
      fact that it was determined from relatively low-resolution laboratory data over a
      limited 2theta range (10-90 degrees 2theta).

PMID- 17507753
TI  - Synchrotron powder diffraction in a systematic study of 4'-[2
      (tosylamino)benzylideneamino]-2,3-benzo-15-crown-5 complexes.
AB  - The crystal structures of two compounds, CuL(2) and LiNCS.HL [HL = 4'-[2
      (tosylamino)benzylideneamino]-2,3-benzo-15-crown-5], have been determined from
      synchrotron powder diffraction data. Both compounds crystallize in the monoclinic
      space group P2(1)/c and with one molecule in the asymmetric unit. In CuL(2) the
      four N atoms of two bidentate L ligands coordinate the Cu(II) ion in a distorted
      tetrahedral geometry with Cu-N distances of 1.98 (5)-2.05 (5) A, while two O
      atoms from two sulfoxide groups complete the distorted octahedral Cu coordination
      [Cu-O 2.64 (4), 2.74 (4) A]. In LiNCS.HL, lithium is coordinated by all five
      ether O atoms with Li-O distances of 2.03 (3)-2.50 (3) A and an N atom from the
      thiocyanate moiety [Li-N 1.98 (3) A] in a distorted pentagonal pyramidal
      geometry. Preliminary potentiometric selectivity measurements for ion-selective
      electrodes (ISEs) based on CuL(2) and ZnL(2) demonstrated significant differences
      in their selectivity. In order to find a possible reason for this, theoretical
      calculations at the DFT (B3LYP) level were performed. These calculations used the
      crystal structures of CuL(2), LiNCS.HL, ZnL(2) and HL as input geometries for the
      minimum energy optimization in vacuo. The results indicate that in ML(2)
      complexes (M = Cu, Zn) the electronic structure of the metal ion determines the
      spatial orientation of benzo-15-crown-5 macrocycles, and their different
      orientation in CuL(2) and ZnL(2) results in different potentiometric
      selectivities of ISEs based on these compounds.

PMID- 17507754
TI  - Structural similarities in tetraaryltins described by virtual non
      crystallographic rotations or translations: Kitaigorodskii's morphotropism is
      revisited.
AB  - Recently Kalman [(2005), Acta Cryst. B61, 536-547] revealed that semirigid
      molecules or their patterns held together e.g. by hydrogen bonds may perform non
      crystallographic rotations (through 180, 90 degrees etc.) around themselves
      whenever a substitution, ring enlargement or isomerization destroys the existing
      close packing, i.e. the novel substituent or the enlarged ring can no longer fit
      in the hollows formed between the molecules. In other words, the old and new
      arrangements of such chemically similar molecules can be converted into each
      other by virtual rotations. However, when a semirigid molecule without
      substitution, but under the influence of solvents, temperature etc., is fully or
      partly rearranged in the solid state, the corresponding non-crystallographic
      rotation (hereinafter ncr) is real and gives rise to polymorphism. Such
      polymorphs are hallmarked by full or partial isostructurality and show that ncrs
      always occur together with isostructurality. First Kitaigorodskii [(1961),
      Organic Chemical Crystallography, New York: Consultants Bureau] reported on the
      structural similarity of three tetraaryltins, (p-RC(6)H(4))(4)Sn, R = H, CH(3),
      CH(3)O, which is terminated by the larger C(2)H(5)O group. A revisit to these
      structures revealed that the tetragonal --> monoclinic conversion termed by
      Kitaigorodskii as a ;morphotropic step' is also performed by an ncr. Similarly,
      other tetraaryltins in the literature are related by ncrs or the nc translation
      of the semirigid tetrahedra, or they remain isostructural. Since one of the
      definitions of morphotropism, a word of Greek origin, is 'turn of form', the ncrs
      of semirigid molecules can be denoted--following Kitaigorodskii--by this word,
      whereas its alternative definition in the morphological crystallography of
      ;unidirectional changes' [applied by Groth (1870). Ber. Chem. Ges. 3, 449-457]
      covers the non-crystallographic translations described first in this work.

PMID- 17507756
TI  - Rapid structure determination of the hydrogen-containing compound Cs2C2O4.H2O by
      joint single-crystal X-ray and powder neutron diffraction.
AB  - The structure determination of caesium oxalate monohydrate using single-crystal X
      ray diffraction, powder neutron diffraction data and a combination of both has
      been undertaken. Results show that even for hydrogen-containing materials data
      collected rapidly on a high-flux neutron diffractometer improve the refinement
      such that accurate positional and thermal displacement parameters can be
      extracted for all atom types. This contrasts with structural models extracted
      from either data set alone that demonstrate the inherent limitations of the
      individual diffraction methods. The rapidity with which useful neutron
      diffraction data has been collected from hydrogen-containing compounds, 10 min in
      this study, indicates that the technique should be widely applicable allowing the
      facile and accurate extraction of hydrogen positions for many compounds.

PMID- 17507755
TI  - Structures of artificial sweeteners--cyclamic acid and sodium cyclamate with
      other cyclamates.
AB  - In the course of a study on artificial sweeteners, new crystal structures of
      cyclamic acid, sodium cyclamate, potassium cyclamate, ammonium cyclamate,
      rubidium cyclamate and tetra-n-propylammonium cyclamate have been determined.
      Cyclamic acid exists in its zwitterionic form in the crystalline state. The
      zwitterions are connected through hydrogen bonds of the N-H...O type to form two
      dimensional sheets. The sodium, potassium, ammonium and rubidium cyclamates are
      isostructural, with the cyclamate moieties linked through hydrogen bonds into
      linear chains. Taking into account the connectivity through cations, two
      dimensional layers with a hydrophobic surface are constructed. In tetra(n
      propyl)ammonium cyclamate the large, non-coordinating cation apparently prevents
      the formation of chains and thereby facilitates the centrosymmetric head-to-head
      discrete dimeric arrangement of the cyclamate moieties.

PMID- 17507757
TI  - Solid-state compounds of stereoisomers: cis and trans isomers of 1,2
      cyclohexanediol and 2,3-tetralindiol.
AB  - The phases of 1,2,3,4-tetrahydro-2,3-naphthalenediol (or 2,3-tetralindiol) and of
      1,2-cyclohexanediol have been investigated. The structure of a very stable 1:1
      compound (or co-crystal) of the cis and trans isomers of 2,3-tetralindiol, the
      existence of which has been known for nearly a century, has finally been
      determined. No evidence of any analogous compound between the cis and trans
      isomers of 1,2-cyclohexanediol has been found. The formation of solid-state
      compounds of stereoisomers is rare; it probably occurs only if the crystal
      packing of at least one of the isomers is unfavorable, e.g. if at least one of
      the melting points is lower than expected. Compound formation is usually unlikely
      because of the difficulty of simultaneously optimizing the translational spacings
      for both isomers, but that packing problem is avoided in the cis/trans compound
      of 2,3-tetralindiol because the two isomers are in very similar environments. In
      the structures of the individual 2,3-tetralindiol isomers there are clear
      conflicts between the competing packing requirements of the 1,2-diol moiety and
      the aromatic ring system; these conflicts are resolved better in the co-crystal
      than in the structures of the individual isomers.

PMID- 17507758
TI  - Tautomerism and hydrogen bonding in guaninium phosphite and guaninium phosphate
      salts.
AB  - The crystal structures of three similar guaninium salts, guaninium
      monohydrogenphosphite monohydrate, C(5)H(6)N(5)O(+).H(2)O(3)P(-).H(2)O, guaninium
      monohydrogenphosphite dihydrate, C(5)H(6)N(5)O(+).H(2)O(3)P(-).2H(2)O, and
      guaninium dihydrogenmonophosphate monohydrate, C(5)H(6)N(5)O(+).H(2)O(4)P(
      ).H(2)O, are described and compared. The crystal structures have been determined
      from accurate single-crystal X-ray data sets collected at 100 (2) K. The two
      phosphite salts are monoclinic, space group P2(1)/c, with different packing and
      the monophosphate salt is also monoclinic, space group P2(1)/n. An investigation
      of the hydrogen-bond network in these guaninium salts reveals the existence of
      two ketoamine tautomers, the N9H form and an N7H form.

PMID- 17507759
TI  - X-ray studies of crystalline complexes involving amino acids and peptides. XLIV.
      Invariant features of supramolecular association and chiral effects in the
      complexes of arginine and lysine with tartaric acid.
AB  - The tartaric acid complexes with arginine and lysine exhibit two stoichiometries
      depending upon the ionization state of the anion. The structures reported here
      are DL-argininium DL-hydrogen tartrate, bis(L-argininium) L-tartrate, bis(DL
      lysinium) DL-tartrate monohydrate, L-lysinium D-hydrogen tartrate and L-lysinium
      L-hydrogen tartrate. During crystallization, L-lysine preferentially interacts
      with D-tartaric acid to form a complex when DL-tartaric acid is used in the
      experiment. The anions and the cations aggregate into separate alternating layers
      in four of the five complexes. In bis(L-argininium) L-tartrate, the amino acid
      layers are interconnected by individual tartrate ions which do not interact among
      themselves. The aggregation of argininium ions in the DL- and the L-arginine
      complexes is remarkably similar, which is in turn similar to those observed in
      other dicarboxylic acid complexes of arginine. Thus, argininium ions have a
      tendency to assume similar patterns of aggregation, which are largely unaffected
      by a change in the chemistry of partner molecules such as the introduction of
      hydroxyl groups or a change in chirality or stoichiometry. On the contrary, the
      lysinium ions exhibit fundamentally different aggregation patterns in the DL-DL
      complexes on the one hand and L-D and L-L complexes on the other. Interestingly,
      the pattern in the L-D complex is similar to that in the L-L complex. The
      lysinium ions in the DL-DL complex exhibit an aggregation pattern similar to
      those observed in the DL-lysine complexes involving other dicarboxylic acids.
      Thus, the effect of change in the chirality of a subset of the component
      complexes could be profound or marginal, in an unpredictable manner. The relevant
      crystal structures appear to indicate that the preference of L-lysine for D
      tartaric acid is perhaps caused by chiral discrimination resulting from the
      amplification of a small energy difference.

PMID- 17507760
TI  - The application of cluster analysis to identify conformational preferences in
      enones and enimines from crystal structural data.
AB  - Cluster analysis can be an effective tool for analysing large quantities of data.
      Here it has been applied to the conformational analysis of enones and enimines in
      the crystalline solid state, using structural information mined from the
      Cambridge Structural Database. The forms that are common in the gaseous state and
      in solution are already known from spectroscopic studies. These forms are also
      found to be the most common conformations observed in the solid state; however,
      the clustering method highlights those structures that do not conform to the
      expected geometries. The study is supported by ab initio gas phase calculations
      on simple enone and enimine fragments.

PMID- 17507761
TI  - Ab initio structure determination of 5-anilinomethylene-2,2-dimethyl-1,3-dioxane
      4,6-dione from laboratory powder data--a combined use of X-ray, molecular and
      solid-state DFT study.
AB  - The crystal structure of the title compound was solved from laboratory powder
      diffraction data in the triclinic group P?bar 1 by simulated annealing using the
      program DASH. Since Rietveld refinements yielded inaccurate geometries the
      structure was finally refined by geometry optimization using energy minimization
      in the solid state with the DFT/plane-waves approach. The molecule is essentially
      planar and its Meldrum's acid moiety (2,2-dimethyl-1,3-dioxane-4,6-dione) has a
      flattened boat conformation. The bond orders in the molecule estimated using a
      natural bond-orbitals formalism correlate with the optimized bond lengths. The
      structure in the solid state is based on dimer units in which the molecules are
      held by N-H...O and C-H...O hydrogen bonds in addition to electrostatic
      interactions. These units interact through weak C-H...O hydrogen bonds. It is
      suggested that structure refinement by energy minimization at the DFT level of
      theory may in many cases successfully replace Rietveld refinement.

PMID- 17507762
TI  - Isostructuralism among bridge-flipped' isomeric benzylideneanilines and
      phenylhydrazones.
AB  - Bridge-flipped' isomers may be defined as pairs of molecules related by a
      reversal of a bridge of atoms connecting two major parts of the individual
      molecules. This kind of isomerism is commonly found among benzylideneanilines and
      phenylhydrazones. Isostructural pairs might be suitable for co-crystallization
      and are thus useful in the preparation of new solid materials. Although most of
      the examples of bridge-flipped isomeric benzylideneanilines and phenylhydrazones
      in the crystallographic literature are not isostructural, a small number of
      isostructural pairs have been reported by previous workers. This paper describes
      the molecular and crystal structures of four pairs of bridge-flipped isomers: two
      isostructural phenylhydrazones, (E)-2-bromobenzaldehyde 4-cyanophenylhydrazone
      (I) and (E)-4-cyanobenzaldehyde 2-bromophenylhydrazone (II); two pairs of
      isostructural benzylideneanilines, N-(2-trifluoromethylbenzylidene)-2
      methylaniline (III) and N-(2-methylbenzylidene)-2-trifluoromethylaniline (IV),
      and N-(2-bromobenzylidene)-2-methylaniline (V) and N-(2-methylbenzylidene)-2
      bromoaniline (VI); and a pair of benzylideneanilines with closely similar unit
      cell dimensions but different packing arrangements, N-(4-methylbenzylidene)-4
      cyanoaniline (VII) and N-(4-cyanobenzylidene)-4-methylaniline (VIII). The
      structure of (V) is disordered. The packing arrangement of (VIII) resembles that
      of the chloro-/methyl-substituted benzylideneanilines MBZCLA/MBZCLB [N-(4
      methylbenzylidene)-4-chloroaniline and N-(4-chlorobenzylidene)-4-methylaniline].
      Although intermolecular hydrogen bonding plays a part in the isostructuralism of
      the two phenylhydrazones, the other examples of isostructuralism occur in the
      absence of similar, relatively strong intermolecular interactions.

PMID- 17507763
TI  - Investigation of hydrogen-bond network in bis(glycinium) oxalate using single
      crystal neutron diffraction and spectroscopic studies.
AB  - Single-crystal neutron diffraction investigation of bis(glycinium) oxalate was
      undertaken in order to study its hydrogen-bonding network, particularly the very
      short hydrogen bond between the glycinum and oxalate ions, indicated by the X-ray
      diffraction study. The non-existence of any phase transition in these crystals
      was attributed to the fact that the short hydrogen bond in bis(glycinium) oxalate
      is asymmetric in nature, with no hydrogen disorder. The potential energy
      landscape for the above-mentioned H atom was found to have a single minimum
      closer to the glycinium ion. IR and Raman investigations of the title complex
      supported the above result.

PMID- 17507764
TI  - Redetermination, invariom-model and multipole refinement of L-ornithine
      hydrochloride.
AB  - The structure of L-ornithine hydrochloride, C(5)H(13)N(2)O2+Cl(-), has been
      redetermined at 100 K by single-crystal X-ray diffraction within a project that
      aims to generate accurate bond-distance restraints for the invariom refinement of
      proteins. The high-resolution data were subject to an invariom and a multipole
      refinement, and the resulting electron densities on a grid were compared.
      Improvements in the conventional R factor obtained by multipole modelling were
      smaller than in other structures containing solely the elements CHNO owing to Cl
      core scattering. Cruickshank's diffraction-component precision index and Stevens
      & Coppens suitability factor are discussed.

PMID- 17507765
TI  - ARMET is a soluble ER protein induced by the unfolded protein response via ERSE
      II element.
AB  - Arginine rich, mutated in early stage of tumors (ARMET) was first identified as a
      human gene highly mutated in a variety of cancers. However, little is known about
      the characteristics of the ARMET protein and its expression. We identified ARMET
      as a gene upregulated by endoplasmic reticulum (ER) stress. Here, we show that
      the mouse homologue of ARMET is an 18-kDa soluble ER protein that is mature after
      cleavage of a signal sequence and has four intramolecular disulfide bonds,
      including two in CXXC sequences. ER stress stimulated ARMET expression, and the
      expression patterns of ARMET mRNA and protein in mouse tissues were similar to
      those of Grp78, an Hsp70-family protein required for quality control of proteins
      in the ER. A reporter gene assay using a mouse ARMET promoter revealed that the
      unfolded protein response of the ARMET gene is regulated by an ERSE-II element
      whose sequence is identical to that of the HERP gene. ARMET is the second fully
      characterized ERSE-II-dependent gene and likely contributes to quality control of
      proteins in the ER.

PMID- 17507766
TI  - [Recombinant DNA experiments involving genetically modified mice].

PMID- 17507767
TI  - [Production of transgenic mice].

PMID- 17507768
TI  - [Gene targeting in embryonic stem cells through homologous recombination].

PMID- 17507769
TI  - [Production of knockout mouse by gene trapping].

PMID- 17507770
TI  - [Mouse bank].

PMID- 17507771
TI  - [A new mechanism of neuropathic pain through ATP receptors in spinal microglia].

PMID- 17507772
TI  - [Study on the mechanism of neuropsychological abnormalities induced by drugs of
      abuse].

PMID- 17507773
TI  - [An overview of therapeutic agents for dysuria].

PMID- 17507774
TI  - [Update on and problems of the drug treatment for voiding dysfunction].

PMID- 17507775
TI  - [Pharmacodynamic profile and clinical efficacy of moxifloxacin ophthalmic
      solution (Vegamox 0.5% ophthalmic solution].

PMID- 17507776
TI  - Roles of RecA protein in spontaneous mutagenesis in Escherichia coli.
AB  - To verify the extent of contribution of spontaneous DNA lesions to spontaneous
      mutagenesis, we have developed a new genetic system to examine simultaneously
      both forward mutations and recombination events occurring within about 600 base
      pairs of a transgenic rpsL target sequence located on Escherichia coli
      chromosome. In a wild-type strain, the recombination events were occurring at a
      frequency comparable to that of point mutations within the rpsL sequence. When
      the cells were UV-irradiated, the recombination events were induced much more
      sharply than point mutations. In a recA null mutant, no recombination event was
      observed. These data suggest that the blockage of DNA replication, probably
      caused by spontaneous DNA lesions, occurs often in normally growing E. coli cells
      and is mainly processed by cellular functions requiring the RecA protein.
      However, the recA mutant strain showed elevated frequencies of single-base
      frameshifts and large deletions, implying a novel mutator action of this strain.
      A similar mutator action of the recA mutant was also observed with a plasmid
      based rpsL mutation assay. Therefore, if the recombinogenic problems in DNA
      replication are not properly processed by the RecA function, these would be a
      potential source for mutagenesis leading to single-base frameshift and large
      deletion in E. coli. Furthermore, the single-base frameshifts induced in the recA
      deficient cells appeared to be efficiently suppressed by the mutS-dependent
      mismatch repair system. Thus, it seems likely that the single-base frameshifts
      are derived from slippage errors that are not directly caused by DNA lesions but
      made indirectly during some kind of error-prone DNA synthesis in the recA mutant
      cells.

PMID- 17507777
TI  - Transposon display for active DNA transposons in rice.
AB  - Transposon display (TD) is a powerful technique to identify the integration site
      of transposons in gene tagging as a functional genomic tool for elucidating gene
      function. Although active endogenous DNA transposons have been used extensively
      for gene tagging in maize, only two active endogenous DNA transposons in rice
      have been identified, the 0.43-kb element mPing of the MITE family and the 0.6-kb
      nDart element of the hAT family. The nDart transposition was shown to be induced
      by crossing with a line containing its autonomous element aDart and stabilized by
      segregating aDart under natural growth conditions, while mPing-related elements
      were shown to transpose in cultured cells, plants regenerated from an anther
      culture, and gamma-ray-irradiated plants. No somaclonal variation should occur in
      nDart-promoted gene tagging because no tissue culture was involved in nDart
      activation. As an initial step to develop an effective tagging system using nDart
      in rice, we tried to visualize GC-rich nDart-related elements comprising 18 nDart
      related sequences of 0.6-kb and 63 nDart-related elements longer than 2 kb in
      Nipponbare by TD. Comparing the observed bands in TD with the anticipated virtual
      bands of the nDart-related elements based upon the available rice genome
      sequence, we have improved our TD protocol by optimizing the PCR amplification
      conditions and are able to visualize approximately 87% of the anticipated bands
      produced from the nDart-related elements. To compare the visualization efficiency
      of these nDart-related elements with that of 50 mPing elements and a unique Ping
      sequence in Nipponbare, we also tried to visualize the mPing-related elements;
      all mPing-related elements are easily visualized. Based on these results, we
      discuss the parameters affecting the visualization efficiencies of these rice DNA
      transposons. We also discuss the utilization of nDart elements in gene tagging
      for functional genomics in rice.

PMID- 17507778
TI  - Dissection of barley chromosome 5H in common wheat.
AB  - We dissected barley chromosome 5H added to common wheat by a genetic method or
      the gametocidal system. Firstly, we induced chromosomal breaks in the offspring
      of a 5H addition line of common wheat carrying a gametocidal chromosome and
      cytologically screened for plants with structural chromosomal changes involving
      5H, such as deletions and translocations. Secondly, we screened the progeny of
      such plants to establish common wheat lines carrying structurally changed
      chromosomes containing single segments of the dissected 5H. Using 23
      representative 5H dissection lines, we physically mapped 97 barley EST markers
      assigned to 5H. The ESTs fell into 20 regions of 5H between the breakpoints of
      the 23 dissected segments, distributing rather evenly along the chromosome, with
      significantly higher frequency in the distal region of the long arm. The ESTs, in
      turn, allowed us to distinguish the breakpoints of dissected 5H segments. We
      demonstrated by PCR (polymerase chain reaction), as well as by in situ
      hybridization, that these dissected 5H segments were stably transmitted in the
      dissection lines. We discuss the usefulness of the 5H dissection lines for
      physical mapping of DNA markers. These 5H dissection lines are available from
      National BioResource Projects-Wheat, Japan.

PMID- 17507779
TI  - The genome size evolution of medaka (Oryzias latipes) and fugu (Takifugu
      rubripes).
AB  - Evolution of the genome size in eukaryotes is often affected by changes in the
      noncoding sequences, for which insertions and deletions (indels) of small
      nucleotide sequences and amplification of repetitive elements are considered
      responsible. In this study, we compared the genomic DNA sequences of two kinds of
      fish, medaka (Oryzias latipes) and fugu (Takifugu rubripes), which show two-fold
      difference in the genome size (800 Mb vs. 400 Mb). We selected a contiguous DNA
      sequence of 790 kb from the medaka chromosome LG22 (linkage group 22), and made a
      precise comparison with the sequence (387 kb) of the corresponding region of
      Takifugu. The sequence of 178 kb in total was aligned common between two fishes,
      and the remaining sequences (612 kb for medaka and 209 kb for fugu) were found
      abundant in various repetitive elements including many types of unclassified low
      copy repeats, all of which accounted for more than a half (54%) of the genome
      size difference. Furthermore, we identified a significant difference in the
      length ratio of the unaligned sequences that locate between the aligned sequences
      (USBAS), particularly after eliminating known repetitive elements. These USBAS
      with no repetitive elements (USBAS-nr) located within the intron and intergenic
      region. These results strongly indicated that amplification of repetitive
      elements and compilation of indels are major driving forces to facilitate changes
      in the genome size.

PMID- 17507780
TI  - Transposable elements in human cancers by genome-wide EST alignment.
AB  - Transposable elements may affect coding sequences, splicing patterns, and
      transcriptional regulation of human genes. Particles of the transposable elements
      have been detected in several tissues and tumors. Here, we report genome-wide
      analysis of gene expression regulated by transposable elements in human cancers.
      We adopted an analysis pipeline for screening methods to detect cancer-specific
      expression from expressed human sequences. We developed a database (TECESdb) for
      understanding the mechanism of cancer development in relation to transposable
      elements. A total of 999 genes fused with transposable elements were found to be
      cancer-related in our analysis of the EST database. According to GO (Gene
      Ontology) analysis, the majority of the 999 cancer-specific genes have functional
      association with gene receptor, DNA binding, and kinase activity. Our data could
      contribute greatly to our understanding of human cancers in relation to
      transposable elements.

PMID- 17507781
TI  - Rad50 is involved in MMS-induced recombination between homologous chromosomes in
      mitotic cells.
AB  - The structural maintenance of chromosomes (SMC) family proteins (Smc1-Smc6)
      typically consist of two coiled-coil domains, an amino-terminal head domain, and
      a carboxyl-terminal tail domain. Rad50, a component of the Mre11/Rad50/Xrs2 (MRX)
      complex, has a similar domain structure to the SMC proteins. In Saccharomyces
      cerevisiae, the MRX complex appears to be essential for recombination between
      homologous chromosomes in meiotic cells, but not in cells undergoing vegetative
      growth. Here we provide for the first time evidence that Rad50, like Smc6, is
      required for the induction of recombination between homologous chromosomes in
      cells in the vegetative growth state upon exposure to methyl methanesulfonate.
      However, UV-induced recombination between homologous chromosomes is intact in
      both rad50 and smc6-56 mutant cells.

PMID- 17507782
TI  - Cryptic long internal repeat sequences in the ribosomal DNA ITS1 gene of the
      dinoflagellate Cochlodinium polykrikoides (dinophyceae): a 101 nucleotide six
      repeat track with a palindrome-like structure.
AB  - Extremely long PCR fragments were generated by PCR amplification of ITS and 5.8S
      rDNA from Cochlodinium polykrikoides against other dinoflagellates. These
      patterns were consistent among geographically different isolates of C.
      polykrikoies. DNA sequencing reactions revealed that the PCR products were 1,166
      bp in length and consisted of 813 bp of ITS1, 160 bp of 5.8S rDNA and 193 bp of
      ITS2. Thus, the long length was caused mainly by the long ITS1 sequence.
      Cryptically, the ITS1 contained a tract of 101 bp that occurs six times in
      tandem. The six repeated elements had identical nucleotide sequences. ITS1,
      therefore, separated three distinct regions: the 5' end (122 bp), the six
      parallel repeats (606 bp), and the 3' region (85 bp). Interestingly, both the
      single and six-repeat sequences should be palindrome-like sequences. In inferred
      secondary structures, both repeat sequences formed a long helical structure. This
      is the first reported discovery of comparatively long internal repeats in the
      ITS1 of dinoflagellates.

PMID- 17507783
TI  - The einkorn wheat (Triticum monococcum) mutant, maintained vegetative phase, is
      caused by a deletion in the VRN1 gene.
AB  - The einkorn wheat (Triticum monococcum) mutant, maintained vegetative phase
      (mvp), was induced by nitrogen ion-beam treatment and was identified by its
      inability to transit from the vegetative to reproductive phase. In our previous
      study, we showed that WAP1 (wheat APETALA1) is a key gene in the regulatory
      pathway that controls phase transition from vegetative to reproductive growth in
      common wheat. WAP1 is an ortholog of the VRN1 gene that is responsible for
      vernalization insensitivity in einkorn wheat. The mvp mutation resulted from
      deletion of the VRN1 coding and promoter regions, demonstrating that WAP1/VRN1 is
      an indispensable gene for phase transition in wheat. Expression analysis of
      flowering-related genes in mvp plants indicated that wheat GIGANTIA (GI),
      CONSTANS (CO) and SUPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) genes either
      act upstream of or in a different pathway to WAP1/VRN1.

PMID- 17507784
TI  - Rat Lefty2/EBAF gene: isolation and expression analysis in the oviduct during the
      early pregnancy stage.
AB  - It has been demonstrated, by RNA Arbitrarily Primed Polymerase Chain Reaction
      (RAP-PCR), that the endometrial bleeding associated factor (ebaf or lefty2) is
      expressed in rat oviduct. In this work we isolated and sequenced the full-length
      lefty2 cDNA from Rattus norvegicus oviducts and described its expression level in
      this organ during the estrous cycle and early pregnancy stage. The coding deduced
      sequence (CDS) codifies a 40.91 kDa protein with a highly conserved TGF-beta
      functional domain. RT-PCR semiquantitative analysis indicated that oviduct cells
      transcribe lefty2 among different stages of the estrous cycle with the maximum
      expression at diestrus phase. The highest expression of lefty2 was at the 4(th)
      day after mating (five folds respect to day one), just when the embryos have
      completed their transit through the oviduct. The lefty2 expression declined
      rapidly thereafter and the levels of their transcripts in the oviduct remained
      low until 7(th) days after mating.

PMID- 17507785
TI  - Pneumatic aorta: aortoesophageal fistula due to chronic aortic dissection.

PMID- 17507786
TI  - New mechanism of organophosphorus pesticide-induced immunotoxicity.
AB  - Organophosphorus pesticides (OPs) are widely used throughout the world as
      insecticides in agriculture and as eradicating agents for termites around homes.
      The main toxicity of OPs is neurotoxicity, which is caused by the inhibition of
      acetylcholinesterase. OPs also affect the immune response, including effects on
      antibody production, interleukin-2 production, T cell proliferation, decrease of
      CD5 cells, and increases of CD26 cells and autoantibodies, Th1/Th2 cytokine
      profiles, and the inhibition of natural killer (NK) cell, lymphokine-activated
      killer (LAK) cell, and cytotoxic T lymphocyte (CTL) activities. However, there
      have been few studies of the mechanism of OP-induced immunotoxicity, especially
      the mechanism of OP-induced inhibition of cytolytic activity of killer cells.
      This study reviews new mechanisms of OP-induced inhibition of the activities of
      NK cells, LAK cells, and CTLs. It has been reported that NK cells, LAK cells, and
      CTLs induce cell death in tumors or virus-infected target cells by two main
      mechanisms. The first mechanism is direct release of cytolytic granules that
      contain the pore-forming protein perforin, several serine proteases termed
      granzymes, and granulysin by exocytosis to kill target cells, which is called the
      granule exocytosis pathway. The second mechanism is mediated by the Fas ligand
      (Fas-L)/Fas pathway, in which FasL (CD95 L), a surface membrane ligand of the
      killer cell cross links with the target cell's surface death receptor Fas (CD95)
      to induce apoptosis of the target cells. To date, it has been reported that OPs
      inhibit NK cell, LAK cell, and CTL activities by at least the following three
      mechanisms: 1) OPs impair the granule exocytosis pathway of NK cells, LAK cells,
      and CTLs by inhibiting the activity of granzymes, and by decreasing the
      intracellular levels of perforin, granzyme A, and granulysin, which were mediated
      by inducing degranulation of NK cells and by inhibiting the transcription of the
      mRNAs of perforin, granzyme A, and granulysin. 2) OPs impair the FasL/Fas pathway
      of NK cells, LAK cells, and CTLs, as investigated by using perforin-knockout
      mice, in which the granule exocytosis pathway of NK cells does not function and
      only the FasL/Fas pathway remains functional. 3) OPs induce apoptosis of immune
      cells.

PMID- 17507787
TI  - Evaluation of parameters of serially monitored F-wave in acute cervical spinal
      cord injury.
AB  - OBJECTIVE: In this study, we aimed to determine how physicians can evaluate the
      severity of acute traumatic spinal cord injury (SCI) and predict the prognosis of
      this injury using the relationships of changes in clinical features and
      electrophysiological examination results. MATERIALS AND METHODS: Serial
      recordings of F-waves were performed on 20 consecutive cervical SCI patients. In
      12 of the patients, changes in several parameters of F-waves which were elicited
      by median and ulnar nerve stimulations were examined by analyzing their
      relationships to clinical symptoms. RESULTS: The maximum amplitude of the F-waves
      (F-max) elicited by median nerve stimulation was found to be the most reliable
      (statistically significant) parameter for distinguishing clinically improved
      patients from nonimproved patients for the prognosis in the early stages after
      trauma. Other parameters, including the incidence of F-waves and the mean F-wave
      amplitude both of which were elicited by median nerve stimulation, were somewhat
      helpful for predicting the prognosis. These parameters of F-waves evoked by ulnar
      nerve stimulation could be useful for several weeks post-trauma.

PMID- 17507789
TI  - Analysis of alteration of blood pressure response to exercise through baroreflex.
AB  - BACKGROUND: The baroreflex has been reported to play an important role in
      hemodynamic regulation during exercise. Therefore, impairment of baroreflex
      function can induce an abnormal response of systolic blood pressure (SBP) to
      exercise, including exercise-induced hypertension. To clarify whether baroreflex
      function alters SBP response, we examined the relationship of baroreflex
      sensitivity (BRS) with SBP response to exercise. METHODS: In 22 subjects without
      cardiac dysfunction, BRS (ms/mmHg) was measured by the phenylephrine method, and
      a treadmill exercise test was administered according to Bruce's protocol.
      RESULTS: 1) The chronotropic response to exercise was higher in the normal BRS
      group than in the reduced BRS group (p<0.01). The SBP at the initial phase of
      exercise (1 min after the start of exercise) showed a smaller increase in the
      normal BRS group than in the reduced BRS group (p<0.01). During the initial phase
      of exercise, BRS had negative correlation with the SBP increment from rest (r=
      0.408, p<0.05). During submaximal exercise (6 min after the start of exercise), a
      positive correlation between BRS and SBP response (r=0.422, p<0.05) was shown. 2)
      Subjects were divided into 2 groups: 12 subjects with normal BRS (> or =5
      ms/mmHg) and 10 subjects with reduced BRS (<5 ms/mmHg). During the initial
      exercise phase, the negative correlation between BRS and SBP response was
      stronger in the normal BRS group (r=-0.398) than in the reduced BRS group (r= 
      0.126). During submaximal exercise, BRS had a positive correlation with BP
      response to exercise in subjects with normal BRS (r=0.462). CONCLUSION: Preserved
      baroreflex function is thought to be related to the pressor response to
      submaximal exercise, although the baroreflex is thought to be associated with the
      stabilization of blood pressure change during the initial exercise phase. These
      findings suggest that exercise-induced hypertension develops through the
      baroreflex mechanism.

PMID- 17507788
TI  - Relationship between plasma norepinephrine at peak exercise and 123I-MIBG imaging
      of the heart and lower limbs in heart failure.
AB  - BACKGROUND: Past studies suggested that plasma norepinephrine during exercise
      originates in sympathetic nerve endings and that the main origin differs among
      pathophysiological conditions. AIMS: This study investigated the most important
      site of sympathetic terminals as an origin of plasma norepinephrine during
      exercise in patients with heart failure using (123)I- metaiodobenzylguanidine
      (MIBG) scintigraphy. METHODS AND RESULTS: Twenty patients with organic heart
      disease underwent exercise testing and (123)I-MIBG scintigraphy. Systemic (123)I
      MIBG uptake was measured 4 hours after (123)I-MIBG injection, and the heart-to
      brain (H/B) and lower limb-to-brain ratios (L/B) were calculated. Plasma
      norepinephrine concentration was measured at rest and at peak exercise. Subjects
      were divided into two groups: those with preserved left ventricular ejection
      fraction (LVEF> or =45%, n=8) and those with reduced LVEF (<45%, n=12). Plasma
      norepinephrine at rest did not correlate with H/B or L/B. In the preserved LVEF
      group, plasma norepinephrine at peak exercise was correlated with H/B (r=0.722),
      but not with L/B. In the reduced LVEF group, the norepinephrine response to peak
      exercise correlated with L/B (r=0.642), but not with H/B. CONCLUSION: The present
      findings suggest that norepinephrine concentration is regulated by sympathetic
      terminal function of working muscles in patients with impaired LVEF and by that
      of the heart in patients with preserved LVEF.

PMID- 17507790
TI  - Dynamics and source of endothelin-1 and interleukin-6 following coronary
      reperfusion in patients with acute myocardial infarction.
AB  - OBJECTIVES: The goals of this study were to determine the source of circulating
      endothelin-1 (ET-1) and interleukin-6 (IL-6) in acute myocardial infarction (MI)
      and to study the effects of coronary reperfusion (CR) on plasma levels of ET-1
      and IL-6. METHODS: We serially measured plasma concentrations of ET-1 and IL-6 at
      different sampling sites before and after CR in patients with acute MI. A femoral
      vein (FV) catheter, a Swan-Ganz catheter, and a femoral artery (FA) catheter were
      placed in 25 patients with acute MI who were admitted within 12 hours after
      onset. For the measurement of ET-1 and IL-6 concentrations, blood samples from
      the FV, right atrium (RA), pulmonary artery (PA), and FA were collected before
      and 1 hour, 8 hours, and 24 hours after CR therapy. In 5 of the 25 patients,
      blood samples were collected through a coronary sinus (CS) catheter. We also
      assessed the gradient across 3 vascular beds (systemic, pulmonary, and coronary)
      as indices of the net release of ET-1 and IL-6 from those vascular beds. The
      maximal serum creatine kinase (CK) levels were assessed as an index of myocardial
      necrosis. RESULTS: ET-1 levels were higher in the FV than in the RA, PA, or FA.
      On CR, ET-1 levels peaked after 1 hour and returned to baseline by 24 hours.
      Calculated net release of ET-1 from the systemic vascular bed (ET-1 at FV-ET-1 at
      FA) was the highest among the 3 vascular beds. Plasma ET-1 levels correlated with
      hemodynamic parameters. Plasma IL-6 levels were similar among different sampling
      sites, whereas calculated net release of IL-6 from the coronary vascular bed was
      the highest among the 3 vascular beds. IL-6 levels increased throughout 24 hours
      after coronary reperfusion and closely correlated with maximal CK levels.
      CONCLUSIONS: The present study suggests that, in acute MI, the major source of ET
      1 maintaining baseline plasma levels is the systemic vascular bed and that the ET
      1 levels presumably reflect the congestion. ET-1 levels peaked 1 hour after CR.
      IL-6 increased for 24 hours after CR. The major source of IL-6 is the coronary
      vascular bed. Only a slight correlation was observed between plasma ET-1 and IL-6
      levels.

PMID- 17507791
TI  - Synergistic induction of apoptosis by p53-inducible Bcl-2 family proteins Noxa
      and Puma.
AB  - One critical tumor-suppressive function of p53 is the induction of apoptosis in
      oncogene-expressing cells. In this context, p53-inducible genes encoding the BH3
      only proteins of the Bcl-2 family, Noxa and Puma, were identified. Gene knockout
      studies revealed that both Noxa and Puma are involved in apoptosis induction in
      oncogene-expressing cells. BH3-only proteins induce apoptosis, and activate the
      downstream apoptosis effectors Bax and Bak. In this study, we found that Noxa and
      Puma synergistically activate Bax and Bak, and induce apoptosis. Although Noxa
      activates Bak by inactivating Mcl-1 and Bcl-X(L), gene knockdown studies revealed
      that neither Mcl-1 nor Bcl-X(L) is involved in this synergism. Moreover, Puma,
      but not Noxa, directly activated Bax in the absence of Bak, and Noxa enhanced
      Puma-mediated Bax activation in Bak-deficient cells. These results suggest the
      existence of a novel regulatory pathway for Noxa-mediated apoptosis. Although we
      detected synergistic induction of apoptosis by Noxa and Bim, a tumor suppressive
      transcriptional factor FoxO3-inducible protein, no such synergism was observed
      for other pairs of BH3-only proteins, Bim and Bid, or Bim and Puma. From these
      results, it can be considered that p53 carefully controls apoptosis by allowing
      two molecules to share full ability to induce apoptosis.

PMID- 17507792
TI  - Usefulness of laparoscopic hepatectomy.
AB  - BACKGROUND: The aim of this study was to investigate the advantages of
      laparoscopic hepatectomy over open surgery for liver tumors. PATIENTS AND METHOD:
      A retrospective study was performed of 10 patients with liver tumors (9 with
      hepatocellular carcinoma and 1 with focal nodular hyperplasia) at our hospital.
      Five patients who had received laparoscopic hepatectomy (Lap-Hx group) were
      compared with 5 patients who had undergone open hepatectomy (O-Hx group) in the
      same period. The operative procedure was partial hepatectomy and cholecystectomy
      in both groups. For liver excision, a microwave coagulation device and an
      ultrasonically activated scalpel were used. RESULTS: Mean patient age was 55.6 +/
      13.9 years in the Lap-Hx group and 51.8 +/- 14.1 years in the O-Hx group. Four
      patients in the Lap-Hx group had hepatocellular carcinoma with liver cirrhosis
      and 1 patient had focal nodular hyperplasia. All patients in the O-Hx group had
      hepatocellular carcinoma and 4 patients had associated liver cirrhosis. The mean
      tumor size was 2.6 +/- 1.5 cm in the Lap-Hx group and 3.0 +/- 1.8 cm in the O-Hx
      group. The two groups did not thus differ significantly in the preoperative
      background factors. Blood loss and duration of the postoperative hospital stay
      were significantly less in the Lap-Hx than in the O-Hx groups(213 +/- 82 vs 247
      +/- 97 min; 154 +/- 128 vs 648 +/- 468 ml, p=0.05: and 10.4 +/- 2.3 vs 18.0 +/-
      5.1 days, p=0.017), but operating time did not differ significantly. CONCLUSIONS:
      Laparoscopic hepatectomy has the advantages of reducing the amount of operative
      blood loss because of the magnified view afforded by the laparoscope and
      shortening the hospital stay. The procedure is therefore recommended for patients
      with appropriate liver tumors, in particular, hepatocellular carcinoma in the
      cirrhotic liver.

PMID- 17507793
TI  - Argon plasma coagulation for the treatment of superficial esophageal carcinoma.
AB  - AIMS: Recently, endoscopic mucosal resection (EMR) has become the first choice of
      treatment for superficial esophageal cancer without metastasis. However, EMR is
      not safe for all patients. Argon plasma coagulation (APC) is a noncontact
      electrocoagulation technique that creates tissue damage. The risk of bleeding may
      be lower with APC than with EMR. Therefore, we selected APC for the treatment of
      patients with superficial esophageal cancer who could not undergo EMR. The aim of
      the present study was to describe these cases and analyze the results of this
      treatment. PATIENTS AND METHODS: Ten patients with superficial esophageal cancer
      underwent APC at our institution from February 2001 through January 2002. None of
      the patients could undergo EMR because of complications. Ablation was performed
      using an APC probe (ERBE APC probe; ERBE Elektromedizin, Tubingen, Germany), a
      high-frequency electrosurgical generator (ERBE ICC200), and an argon delivery
      unit (ERBE APC 300). All patients had uneventful recoveries. RESULTS: No
      incidents of bleeding from the ablated lesion or infection occurred. Oral intake
      was resumed on the day after treatment. The mean duration of the procedure was 20
      minutes (range, 10 to 40 minutes). Disease recurred in two patients. Two patients
      died of laryngeal cancer and liver failure, respectively. CONCLUSION: APC is a
      safe and easy to perform procedure, but the effect of therapy is inferior to that
      of EMR in terms of the complete resection of the lesion. In conclusion, APC
      should be limited to cases of superficial esophageal cancer without metastasis in
      which EMR has been deemed difficult.

PMID- 17507794
TI  - Case of intra-abdominal endocrine tumor possibly arising from an ectopic
      pancreas.
AB  - We report an intra-abdominal endocrine tumor possibly arising from an ectopic
      pancreas. A 45-year-old woman visited the Nippon Medical School Musashi-Kosugi
      Hospital because of right-sided hypochondralgia and upper abdominal discomfort of
      1 years duration. An intra-abdominal tumor was diagnosed on the basis of the
      results of an ultrasound examination, computed tomography and magnetic resonance.
      Surgery was subsequently performed using laparoscopic techniques, and a tumor
      without firm adhesions was found near the wall of the duodenal bulbus. The tumor
      was easily removed; the resected specimen (55 x 45 x 25 mm, 50 g) was composed of
      bloody fluid within a cystic tumor. Histological and immunohistochemical
      examinations of the tumor showed a type 3 ectopic pancreas, according to the
      classification proposed by Heinrich. The patients recovery was uneventful.

PMID- 17507795
TI  - Repair of recoarctation and aortic valve replacement with the On-X valve in a
      pediatric patient: a case report.
AB  - A 10-year-old boy had undergone conventional two-stage surgery that included
      repair of aortic coarctation with pulmonary artery banding as an initial
      operation followed by closure of a ventricular septal defect as a secondary
      procedure. Following these procedures, aortic coarctation recurred, and balloon
      angioplasty was performed three times. Aortic recoarctation, however, persisted,
      and aortic stenosis and regurgitation and pulmonary stenosis gradually developed.
      An operation was therefore performed to repair recoarctation, aortic stenosis and
      regurgitation, and pulmonary stenosis. Patch aortoplasty was performed for
      recoarctation. The aortic valve was replaced with a 19 mm On-X valve, with Konno
      root enlargement. Pulmonary arterial patch plasty was also performed. During
      aortic arch reconstruction, selective cerebral perfusion was performed via the
      innominate artery and left carotid artery, and the lower half of the body was
      perfused through a cannula in the left femoral artery. The postoperative course
      was uneventful, and aortography revealed a well-reconstructed aortic arch free of
      obstruction. There were no valve-related complications.

PMID- 17507796
TI  - Exploiting the TRIP-Br family of cell cycle regulatory proteins as
      chemotherapeutic drug targets in human cancer.
AB  - TRIP-Br1 and TRIP-Br2 are potent cell growth promoting factors that function as
      components of the E2F1/DP1 transcription complex to integrate positive growth
      signals provided by PHD zinc finger- and/or bromodomain-containing transcription
      factors. TRIP-Br1 has been demonstrated to be an oncogene. We recently reported
      that antagonism of the TRIP-Br integrator function by synthetic decoy peptides
      that compete with TRIP-Br for binding to PHD zinc finger- and/or bromodomain
      containing proteins elicit an anti-proliferative effect and induces caspase-3
      independent sub-diploidization in cancer cells in vitro. We now demonstrate the
      chemotherapeutic potential of TRIP-Br decoy peptides for the treatment of
      cutaneous and intracavitary lesions in vitro as well as in vivo in representative
      human nasopharyngeal cancer (CNE2), cervical cancer (Ca Ski) and melanoma (MeWo)
      cancer cell lines. In vitro, BrdU incorporation, colony formation assays and cell
      cycle analysis confirmed that TRIP-Br decoy peptides possess strong anti
      proliferative effects and induce nuclear sub-diploidization in cancer cells. In
      vivo, CNE2, Ca Ski and MeWo-derived chick embryo chorioallantoic membrane (CAM)
      tumor xenografts were used to evaluate the effect of topically applied TRIP-Br
      peptides. Confocal microscopy and flow cytometric analysis demonstrated that
      cells comprising the tumor xenografts efficiently internalized topically applied
      FITC-labeled peptides. Fifty muM of TRIP-Br1 decoy peptide significantly
      suppressed the growth of NPC2-derived human nasopharyngeal tumors, while 50 muM
      of TRIP-Br2 decoy peptide significantly inhibited tumor growth in all three CAM
      tumor xenograft models. Two hundred muM of TRIP-Br1 decoy peptide significantly
      inhibited MeWo-derived tumors. These results suggest that the TRIP-Br integrator
      function may represent a novel chemotherapeutic target for the treatment of human
      cutaneous and intracavitary proliferative lesions.

PMID- 17507797
TI  - PKC delta and tissue transglutaminase are novel inhibitors of autophagy in
      pancreatic cancer cells.
AB  - Apoptosis (type I) and autophagy (type II) are both highly regulated forms of
      programmed cell death and play crucial roles in physiological processes such as
      the development, homeostasis and selective, moderate to massive elimination of
      cells, if needed. Accumulating evidence suggests that cancer cells, including
      pancreatic cancer cells, in general tend to have reduced autophagy relative to
      their normal counterparts and premalignant lesions, supporting the contention
      that defective autophagy provides resistance to metabolic stress such as hypoxia,
      acidity and chemotherapeutics, promotes tumor cell survival and plays a role in
      the process of tumorigenesis. However, the mechanisms underlying the reduced
      capability of undergoing autophagy in pancreatic cancer remain elusive. In a
      recent study, we demonstrated a novel mechanism for regulation of autophagy in
      pancreatic ductal carcinoma cells. We found that protein kinase C-delta (PKC
      delta) constitutively suppresses autophagy through induction of tissue
      transglutaminase (TG2). Inhibition of PKC delta/TG2 signaling resulted in
      significant autophagic cell death that was mediated by Beclin 1. Elevated
      expression of TG2 in pancreatic cancer cells has been implicated in the
      development of drug resistance, metastatic phenotype and poor patient prognosis.
      In conclusion, our data suggest a novel role of PKC delta/TG2 in regulation of
      autophagy, and that TG2 may serve as an excellent therapeutic target in
      pancreatic cancer cells.

PMID- 17507798
TI  - Speedy/RINGO regulation of CDKs in cell cycle, checkpoint activation and
      apoptosis.
AB  - Speedy/RINGO family members bind and activate cyclin dependent kinases (CDKs),
      although these proteins have no homology to known cyclin proteins. Members of
      this family are required for and enhance meiotic maturation, in addition to
      having novel roles in regulating the mitotic mammalian cell cycle and the DNA
      damage response. Here we discuss how the specialized functions of these proteins
      differ from classical cyclin-mediated activation of CDKs. Through atypical
      activation of CDKs, bypass of conventional inhibitory mechanisms, and unique
      substrate selection, Speedy/RINGO proteins contribute to cell cycle, checkpoint,
      and apoptotic regulation. Furthermore, we address the recently established
      correlation between Spy1 and cancer in terms of the specialized functions of the
      Speedy/RINGO family.

PMID- 17507799
TI  - E2F4 function in G2: maintaining G2-arrest to prevent mitotic entry with damaged
      DNA.
AB  - Mammalian cells undergo cell cycle arrest in response to DNA damage through
      multiple checkpoint mechanisms. One such checkpoint pathway maintains genomic
      integrity by delaying mitotic progression in response to genotoxic stress.
      Transition though the G2 phase and entry into mitosis is considered to be
      regulated primarily by cyclin B1 and its associated catalytically active partner
      Cdk1. While not necessary for its initiation, the p130 and Rb-dependent target
      genes have emerged as being important for stable maintenance of a G2 arrest. It
      was recently demonstrated that by interacting with p130, E2F4 is present in the
      nuclei and plays a key role in the maintenance of this stable G2 arrest.
      Increased E2F4 levels and its translocation to the nucleus following genotoxic
      stress result in downregulation of many mitotic genes and as a result promote a
      G0-like state. Irradiation of E2F4-depleted cells leads to enhanced cellular DNA
      double-strand breaks that may be measured by comet assays. It also results in
      cell death that is characterized by caspase activation, sub-G1 and sub-G2 DNA
      content, and decreased clonogenic cell survival. Here we review these recent
      findings and discuss the mechanisms of G2 phase checkpoint activation and
      maintenance with a particular focus on E2F4.

PMID- 17507800
TI  - Silencing of LMP1 induces cell cycle arrest and enhances chemosensitivity through
      inhibition of AKT signaling pathway in EBV-positive nasopharyngeal carcinoma
      cells.
AB  - The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is closely
      associated with nasopharyngeal carcinoma (NPC). In this study, we investigated
      that the effect of silencing LMP1 on cell cycle distribution and chemosensitivity
      in EBV-positive naso-pharyngeal carcinoma C666-1 cells. Silencing of LMP1 by
      specific siRNA induced G1 arrest in C666-1 cells. The protein expression of CDK4
      and cyclin D1 decreased and P27 was upregulated following LMP1 knockdown.
      Phosphorylation of AKT and its downstream targets IkappaB, FKHR was inhibited by
      LMP1 siRNA. The chemosensitivity of C666-1 cells to bleomycin and cisplatin was
      enhanced by siRNA targeting LMP1. The cells treated with LMP1 siRNA showed
      enhanced cleavage of the effector caspase3 and PARP, and Bax had the tendency to
      exhibit higher expression. Also, cotransfection of constitutive active AKT
      plasmid with LMP-1 siRNA plasmid abrogates sensitivity of C666-1 to bleomycin and
      cisplatin. It is reported for the first time that AKT signaling pathway was
      directly involved in the effects induced by siRNA targeting LMP1. Our findings
      confirm LMP1 as a rational therapeutic target in NPC.

PMID- 17507801
TI  - Regulation of intracellular MEK1/2 translocation in mouse oocytes: cytoplasmic
      dynein/dynactin-mediated poleward transport and cyclin B degradation-dependent
      release from spindle poles.
AB  - We recently reported that MEK1/2 plays an important role in microtubule
      organization and spindle pole tethering in mouse oocytes, but how the
      intracellular transport of this protein is regulated remains unknown. In the
      present study, we investigated the mechanisms of poleward MEK1/2 transport during
      the prometaphase I/metaphase I transition and MEK1/2 release from the spindle
      poles during the metaphase I/anaphase I transition in mouse oocytes. Firstly, we
      found that p-MEK1/2 was colocalized with dynactin at the spindle poles.
      Inhibition of the cytoplasmic dynein/dynactin complex by antibody microinjection
      blocked polar accumulation of p-MEK1/2 and caused obvious spindle abnormalities.
      Moreover, coimmunoprecipitation of p-MEK1/2 and dynein or dynactin from mouse
      oocyte extracts confirmed their association at metaphase I. Secondly, disruption
      of microtubules by nocodazole resulted in the failure of poleward p-MEK1/2
      transport. Whereas, when the nocodazole-treated oocytes were recovered in fresh
      culture medium, the spindle reformed and p-MEK1/2 relocalized to the spindle
      poles. Finally, we examined the mechanism of p-MEK1/2 release from the spindle
      poles. In control oocytes, polar p-MEK1/2 was gradually released during metaphase
      I/anaphase I transition. By contrast, in the presence of nondegradable cyclin B
      (Delta90), p-MEK1/2 still remained at the spindle poles at anaphase I. Our
      results indicate that poleward MEK1/2 transport is a cytoplasmic dynein/dynactin
      mediated and spindle microtubule-dependent intracellular movement, and that its
      subsequent anaphase release from spindle poles is dependent on cyclin B
      degradation.

PMID- 17507802
TI  - Reproducibility of quantitative cerebral T2 relaxometry, diffusion tensor
      imaging, and 1H magnetic resonance spectroscopy at 3.0 Tesla.
AB  - OBJECTIVES: The reproducibility of quantitative cerebral T2 relaxometry,
      diffusion tensor imaging, and H magnetic resonance (MR) spectroscopic imaging was
      assessed on a clinical 3.0 T MR system. MATERIALS AND METHODS: Repeated
      measurements in 10 healthy volunteers were used to establish the reproducibility
      of quantitative measures derived from different quantitative MR techniques,
      namely the T2 relaxation time, the apparent diffusion coefficient (ADC), the
      fractional anisotropy (FA), and metabolite concentrations of N-acetyl-aspartate
      (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI). Results were compared
      with previously reported reproducibility measures from 1.5 T. RESULTS: The
      coefficient of variation (CV) was < or =1.6% for T2, < or =1.6% for ADC, and < or
      =5.3%, for FA in the cerebrum. For metabolites the CV was < or =8.0% in the
      frontal lobe and < or =20.4% in the temporal lobe. CONCLUSIONS: The
      reproducibility of quantitative brain MRI at 3.0 T is better than or at least
      comparable to the reproducibility at 1.5 T.

PMID- 17507803
TI  - Diffusion-tensor imaging at 3 T: detection of white matter alterations in
      neurological patients on the basis of normal values.
AB  - OBJECTIVE: Fractional anisotropy (FA) is a powerful measure to study the
      integrity of the cerebral white matter in vivo. However, because clinical FA
      assessments are frequently based on single slice evaluations, intra- and
      interindividual comparisons are highly dependent on image alignment. We attempted
      to develop an observer-independent, fully automated technique for quantitative FA
      assessment. MATERIALS AND METHODS: We employed whole brain diffusion tensor
      imaging at 3 T with an echo planar imaging sequence (isotropic spatial resolution
      1.8 mm) on 4 patients (2x Alzheimer disease, 1x microangiopathy, 1x
      paraneoplastic disease) and 2 normal control groups (group "young," age 19-32
      years; group "old," age 59-69 years). The images were spatially normalized to the
      standard brain template of the Montreal Neurologic Institute. We introduced a
      fractional anisotropy index (FAI) as a single measure for the mean tissue
      anisotropy in certain brain regions of interest. The regions of interest were
      defined by masks in relation to the Montreal Neurologic Institute coordinate
      space. We varied the spatial extent of the masks. Confidence intervals of the
      FAIs for both control groups were calculated. RESULTS: We found the resulting
      FAIs to be highly robust against considerable mask variations (product-moment
      correlation: r > 0.97). The FAIs of the 4 patients presented with neurologic
      conditions associated with white matter alterations significantly fell outside
      the confidence intervals for normal FA. CONCLUSION: FAIs based on mean fractional
      anisotropy values obtained from isotropic whole-head high-field diffusion tensor
      imaging by fully automated algorithms represent a robust and observer-independent
      measure for the comparative assessment of white matter integrity, ideally suited
      for further statistical treatments.

PMID- 17507804
TI  - Improved preoperative evaluation of cerebral cavernomas by high-field, high
      resolution susceptibility-weighted magnetic resonance imaging at 3 Tesla:
      comparison with standard (1.5 T) magnetic resonance imaging and correlation with
      histopathological findings--preliminary results.
AB  - OBJECTIVES: To compare high-field, high-resolution, susceptibility-weighted
      magnetic resonance imaging (3 Tesla [T] HR-SW-MRI) and standard (1.5 Tesla [T])
      MRI for the detection of cerebral cavernomas. To evaluate the ability of 3 T HR
      SW-MRI to visualize intralesional structures compared with standard (1.5 T) MRI,
      in correlation with histopathologic findings. MATERIALS AND METHODS: Seventeen
      patients with cerebral cavernomas underwent both standard (1.5 T) MRI (T1-SE, T2
      TSE, T2*-GRE) and 3 T HR-SW-MRI (TR/TE 43.3/9.1 millisecond; 512 x 384 x 48
      matrix; FOV 250 mm; SI 72 mm) at our institution. All MR images were evaluated by
      3 radiologists in consensus for detectability, size (</>1 cm), and conspicuity
      (good, acceptable, poor) of the lesions at both field strengths, and for the
      presence of hypointense intralesional tubular structures. In 7 patients, MR
      findings were correlated with histopathologic findings. RESULTS: Both 3 T HR-SW
      MRI and standard (1.5 T) MRI detected 22 lesions in 17 patients; 3 T HR-SW-MRI
      detected an additional 7 lesions in 6 patients. On average, 3 T HR-SW-MRI
      detected 1.706 +/- 0.92 (median = 1) lesions per patient, whereas standard (1.5
      T) MRI detected 1.235 +/- 0.664 lesions per patient (P = 0.016). Lesion
      conspicuity was good in all 3 T HR-SW-MR images and good in 68.2% and acceptable
      in 31.8% of standard (1.5 T) MR images (P = 0.016). In 22 lesions detected at
      both field strengths, 3 T HR-SW-MRI demonstrated intralesional tubular structures
      in 72.7% and standard (1.5 T) MRI demonstrated these structures in 31.8% (P =
      0.001). Intralesional tubular structure correlated to conglomerates of cavernous
      vessel, as verified by histopathology. CONCLUSION: Compared with standard (1.5 T)
      MRI, 3 T HR-SW-MRI allows superior detection and characterization of cerebral
      cavernomas. Despite increased susceptibility effects, ie, signal loss at higher
      magnetic field strengths, the visualization of intralesional tubular structures
      is feasible. This may be helpful in the diagnosis, presurgical planning, and
      noninvasive follow-up after gamma-knife radiosurgery.

PMID- 17507805
TI  - Contrast-enhanced first-pass myocardial perfusion magnetic resonance imaging with
      parallel acquisition at 3.0 Tesla.
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) at 3 T is significantly different
      than 1.5 T and needs to be optimized due to increased signal-to-noise ratio (SNR)
      and specific absorption ratio (SAR). This study tests the hypothesis that first
      pass myocardial perfusion MRI using saturation recovery (SR)-TrueFISP with
      parallel imaging is superior to SR-TurboFLASH and a more achievable technique for
      clinical application at 3 T. MATERIALS AND METHODS: Myocardial perfusion imaging
      was performed on 12 subjects using SR-TurboFLASH and SR-TrueFISP sequences
      combined with parallel imaging. Four myocardial slices were acquired and
      evaluated by image segmentation. Quality of the measurements was determined from
      SNR, contrast-to-noise ratio (CNR), enhancement-to-noise ratio (ENR), and
      myocardial perfusion upslope. Data were analyzed using a 2-way ANOVA with imaging
      method and segment number as the independent variables. RESULTS: SNR, CNR, ENR,
      and upslope were significantly higher for SR-TrueFISP versus SR-TurboFLASH (P <
      0.001). Significant differences in SNR, CNR, ENR, and upslope were found among
      the myocardial segments (P < 0.005). CONCLUSIONS: Optimized SR-TrueFISP first
      pass myocardial perfusion MRI at 3 T has superior image quality compared with SR
      TurboFLASH, independent of the myocardial segment analyzed. However, coil
      sensitivity nonuniformities and dielectric resonance effects cause signal
      intensity differences between myocardial segments that must be accounted for when
      interpreting 3 T perfusion studies.

PMID- 17507806
TI  - Inversion recovery single-shot TurboFLASH for assessment of myocardial infarction
      at 3 Tesla.
AB  - PURPOSE: The aim of the study was to assess the diagnostic accuracy of imaging
      myocardial infarction with a single-shot inversion recovery turbofast low-angle
      shot (SS IR turboFLASH) sequence at 3.0 Tesla in comparison with an established
      segmented inversion recovery turboFLASH sequence at 1.5 Tesla. MATERIALS AND
      METHODS: Fifteen patients with myocardial infarction were examined at a 1.5 Tesla
      magnetic resonance (MR) System (Avanto, Siemens, Medical Solutions) and at a 3.0
      Tesla MR system (TIM Trio, Siemens, Medical Solutions). Imaging delayed
      enhancement was started 15 minutes after application of contrast material. A SS
      IR turboFLASH was performed at 3.0 Tesla and compared with a segmented IR
      turboFLASH sequence at 1.5 and at 3.0 Tesla. The IR turboFLASH sequence at 1.5
      Tesla served as reference method. Infarct volumes, contrast/noise ratio (CNR) of
      infarcted and normal myocardium were compared with the reference method. RESULTS:
      The Single-Shot IR turboFLASH technique allows imaging 9 slices during a single
      breath-hold. The CNR between infarction and normal myocardium of the reference
      method was 6.4 at 1.5 Tesla. The mean value of CNR of the IR turboFLASH sequence
      was 7.3 at 3.0 Tesla for the single-shot technique and 14.1 at 3.0 Tesla for the
      segmented technique. No significant difference was found for the CNR values of
      the reference technique at 1.5 Tesla and the single-shot technique at 3.0 Tesla,
      however for the comparison of the segmented technique at 1.5 and at 3 Tesla (P =
      0.0001). The correlation coefficients of the infarct volumes, determined with the
      Single-Shot IR turboFLASH and the segmented IR turboFLASH technique at 3.0
      compared with the reference method, were r = 0.95 (P < 0.0001) and r = 0.95 (P <
      0.0001). CONCLUSION: The loss of CNR, which is caused by replacement of the
      segmented technique by the single-shot technique, is completely compensated by
      the approximately 2-fold CNR increase at the higher field strength. The IR
      turboFLASH technique at 3.0 Tesla IR can be used as a single-shot technique with
      acquisition of 9 slices during a single breath-hold without loss of diagnostic
      accuracy compared with the segmented technique at 1.5 Tesla.

PMID- 17507807
TI  - Comparison of the extent of delayed-enhancement cardiac magnetic resonance
      imaging with and without phase-sensitive reconstruction at 3.0 T.
AB  - OBJECTIVES: To evaluate phase-sensitive reconstructed images versus magnitude
      images generated by an inversion recovery pulse sequence for the determination of
      myocardial infarct size in delayed-enhancement cardiac magnetic resonance (DE
      CMR) at 3 T. MATERIALS AND METHODS: Thirty patients were examined at 3 T and DE
      images were obtained 10 minutes after contrast agent administration using a phase
      sensitive breath-hold segmented inversion recovery gradient echo sequence. From
      magnitude and phase images, the percentage of hyperenhanced myocardium was
      expressed. Contrast-to-noise ratio (CNR) measurements were performed in
      hyperenhanced and normal myocardium. RESULTS: We observed excellent correlation
      and concordance between hyperenhanced myocardium determined on phase-sensitive
      reconstructed and magnitude images. The mean CNR values were significantly higher
      in phase-sensitive reconstructed images compared with magnitude images (10.5 +/-
      5.4 vs. 6.1 +/- 4.8; P < 0.001). CONCLUSIONS: DE-CMR with phase-sensitive
      reconstruction at 3.0 T provides similar results to magnitude images, but with a
      significantly greater CNR between infarcted and normal myocardium.

PMID- 17507808
TI  - Lung MRI at 1.5 and 3 Tesla: observer preference study and lesion contrast using
      five different pulse sequences.
AB  - OBJECTIVES: To compare the image quality and lesion contrast of lung MRI using 5
      different pulse sequences at 1.5 T and 3 T. MATERIALS AND METHODS: Lung MRI was
      performed at 1.5 T and 3 T using 5 pulse sequences which have been previously
      proposed for lung MRI: 3D volumetric interpolated breath-hold examination (VIBE),
      true fast imaging with steady-state precession (TrueFISP), half-Fourier single
      shot turbo spin-echo (HASTE), short tau inversion recovery (STIR), T2-weighted
      turbo spin-echo (TSE). In addition to 4 healthy volunteers, 5 porcine lungs were
      examined in a dedicated chest phantom. Lung pathology (nodules and infiltrates)
      was simulated in the phantom by intrapulmonary and intrabronchial injections of
      agarose. CT was performed in the phantom for correlation. Image quality of the
      sequences was ranked in a side-by-side comparison by 3 blinded radiologists
      regarding the delineation of pulmonary and mediastinal anatomy, conspicuity of
      pulmonary nodules and infiltrates, and presence of artifacts. The contrast of
      nodules and infiltrates (CNODULES and CINFILTRATES) defined by the ratio of the
      signal intensities of the lesion and adjacent normal lung parenchyma was
      determined. RESULTS: There were no relevant differences regarding the preference
      for the individual sequences between both field strengths. TSE was the preferred
      sequence for the visualization of the mediastinum at both field strengths. For
      the visualization of lung parenchyma the observers preferred TrueFISP in
      volunteers and TSE in the phantom studies. At both field strengths VIBE achieved
      the best rating for the depiction of nodules, whereas HASTE was rated best for
      the delineation of infiltrates. TrueFISP had the fewest artifacts in volunteers,
      whereas STIR showed the fewest artifacts in the phantom. For all but the TrueFISP
      sequence the lesion contrast increased from 1.5 T to 3 T. At both field strengths
      VIBE showed the highest CNODULES (6.6 and 7.1) and HASTE the highest CINFILTRATES
      (6.1 and 6.3). CONCLUSION: The imaging characteristics of different pulse
      sequences used for lung MRI do not substantially differ between 1.5 T and 3 T. A
      higher lesion contrast can be expected at 3 T.

PMID- 17507809
TI  - Hyperpolarized 3He ventilation defects and apparent diffusion coefficients in
      chronic obstructive pulmonary disease: preliminary results at 3.0 Tesla.
AB  - OBJECTIVE: Hyperpolarized 3He magnetic resonance imaging (3He MRI) at 3.0 Tesla
      of healthy volunteers and chronic obstructive pulmonary disease (COPD) patients
      was performed for quantitative evaluation of ventilation defects and apparent
      diffusion coefficients (ADC) and for comparison to published results acquired at
      1.5 Tesla. The reproducibility of 3He ADC and ventilation defects was also
      assessed in subjects scanned 3 times, twice within 10 minutes, and again within 7
      +/- 2 days of the first MRI visit. MATERIALS AND METHODS: Hyperpolarized 3He MRI
      was performed in 6 subjects. Two interleaved images with and without additional
      diffusion sensitization were acquired with the first image serving as a
      ventilation image from which defect score and volume were measured and the
      combination of the 2 images used to compute ADC maps and ADC histograms. RESULTS:
      He MRI at 3.0 Tesla showed increased mean ADC and ADC standard deviation for
      subjects with COPD compared with healthy volunteers (ADC healthy volunteer (0.24
      +/- 0.12 cm2/s), mild-moderate COPD (0.34 +/- 0.14 cm2/s), and severe COPD (0.47
      +/- 0.21 cm2/s), and these values were similar to previously reported results
      acquired at 1.5 Tesla. Reproducibility of mean ADC was high (coefficient of
      variation 2% in severe COPD, 3% in mild-moderate COPD, 4% in healthy volunteers)
      across all 3 scans. Higher same-day scan reproducibility was observed for
      ventilation defect volume compared with 1-week scan reproducibility in this small
      group of subjects. CONCLUSIONS: ADC values for emphysematous lungs were
      significantly increased compared with healthy lungs in age-matched subjects, and
      all values were comparable to those reported previously at 1.5 Tesla. Ventilation
      defect score and ventilation defect volume results were also comparable to
      results previously reported in COPD subjects Reproducibility of ADC for same-day
      scan-rescan and 7-day rescan was high and similar to previously reported results.

PMID- 17507810
TI  - 3.0 Tesla high spatial resolution contrast-enhanced magnetic resonance
      angiography (CE-MRA) of the pulmonary circulation: initial experience with a 32
      channel phased array coil using a high relaxivity contrast agent.
AB  - PURPOSE: To evaluate the technical feasibility of high spatial resolution
      contrast-enhanced magnetic resonance angiography (CE-MRA) with highly accelerated
      parallel acquisition at 3.0 T using a 32-channel phased array coil, and a high
      relaxivity contrast agent. MATERIALS AND METHODS: Ten adult healthy volunteers (5
      men, 5 women, aged 21-66 years) underwent high spatial resolution CE-MRA of the
      pulmonary circulation. Imaging was performed at 3 T using a 32-channel phase
      array coil. After intravenous injection of 1 mL of gadobenate dimeglumine (Gd
      BOPTA) at 1.5 mL/s, a timing bolus was used to measure the transit time from the
      arm vein to the main pulmonary artery. Subsequently following intravenous
      injection of 0.1 mmol/kg of Gd-BOPTA at the same rate, isotropic high spatial
      resolution data sets (1 x 1 x 1 mm3) CE-MRA of the entire pulmonary circulation
      were acquired using a fast gradient-recalled echo sequence (TR/TE 3/1.2
      milliseconds, FA 18 degrees) and highly accelerated parallel acquisition (GRAPPA
      x 6) during a 20-second breath hold. The presence of artifact, noise, and image
      quality of the pulmonary arterial segments were evaluated independently by 2
      radiologists. Phantom measurements were performed to assess the signal-to-noise
      ratio (SNR). Statistical analysis of data was performed by using Wilcoxon rank
      sum test and 2-sample Student t test. The interobserver variability was tested by
      kappa coefficient. RESULTS: All studies were of diagnostic quality as determined
      by both observers. The pulmonary arteries were routinely identified up to fifth
      order branches, with definition in the diagnostic range and excellent
      interobserver agreement (kappa = 0.84, 95% confidence interval 0.77-0.90).
      Phantom measurements showed significantly lower SNR (P < 0.01) using GRAPPA (17.3
      +/- 18.8) compared with measurements without parallel acquisition (58 +/- 49.4).
      CONCLUSION: The described 3 T CE-MRA protocol in addition to high T1 relaxivity
      of Gd-BOPTA provides sufficient SNR to support highly accelerated parallel
      acquisition (GRAPPA x 6), resulting in acquisition of isotopic (1 x 1 x 1 mm3)
      voxels over the entire pulmonary circulation in 20 seconds.

PMID- 17507811
TI  - Magnetic resonance (MR) cholangiography: quantitative and qualitative comparison
      of 3.0 Tesla with 1.5 Tesla.
AB  - OBJECTIVES: To determine quantitative and qualitative image quality in patients
      undergoing magnetic resonance (MR) cholangiography at 3.0 Tesla (T) compared with
      1.5 T. MATERIALS AND METHODS: Fifty patients (30 women; mean age, 51 years)
      underwent MR cholangiography at 1.5 T; another 50 patients (25 women; mean age 51
      years) were scanned at 3.0 T. MR sequence protocol consisted of breath-hold
      single-slice rapid acquisition with relaxation enhancement (RARE) and a
      respiratory-triggered 3D turbo spin echo (3D TSE) sequence. Maximum intensity
      projections were generated from the 3D TSE datasets. Contrast-to-noise ratio
      (CNR) measurements between the common bile duct (CBD), left and right
      intrahepatic duct (LHD, RHD), and periductal tissue were performed. Three
      radiologists assessed qualitatively the visibility of the CBD, LHD, and RHD and
      the overall diagnostic quality. RESULTS: Mean gain in CNR at 3.0 T versus 1.5 T
      in all 3 locations ranged for the RARE sequence from 7.7% to 38.1% and for the 3D
      TSE from 0.5% to 26.1% (P > 0.05 for all differences). Qualitative analysis did
      not reveal any significant difference between the 2 field strengths (P > 0.05).
      CONCLUSIONS: MR cholangiography at 3.0 T shows a trend toward higher CNR without
      improving image quality significantly.

PMID- 17507812
TI  - Intraindividual comparison of MR-renal perfusion imaging at 1.5 T and 3.0 T.
AB  - PURPOSE: The purpose of this study was to intraindividually compare fast gradient
      echo semiquantitative renal perfusion measurements at 1.5 Tesla (T) and 3.0
      Tesla. MATERIALS AND METHODS: Fifteen healthy male volunteers underwent renal
      perfusion measurements at 1.5 T and 3.0 T after the bolus injection of 7 mL of Gd
      BOPTA. At both field strengths a Saturation-Recovery-fast gradient echo sequence
      (SR-TurboFLASH) with a temporal resolution of 4 (1.5 T) and 5 (3.0 T)
      simultaneously acquired slices per second was used. At 3.0 T, a parallel-imaging
      factor 2 was applied. For postprocessing, semiquantitative perfusion parameters
      including mean transit time (MTT), time to peak (TTP), and maximal signal
      intensity (SMax) were determined. The signal-to-noise ratios (SNR) of kidneys and
      aorta were determined precontrast and after enhancement. The image quality was
      rated by 2 radiologists. After Bonferroni correction paired t-tests were
      performed for statistical analysis. RESULTS: All measurements were successfully
      performed. At 3.0 T, a significant 63% increase in the baseline SNR (P = 0.00005)
      of the kidneys was found, the peak SNR was also increased though not
      statistically significant. Because of the higher SNR, the SMax was also
      significantly (P = 0.005) increased from 406 A.U. to 522 A.U., whereas MTT and
      TTP were not significantly changed. The image quality was rated very good to good
      for the 3.0 T images but only good to moderate at 1.5 T. CONCLUSION: Renal
      perfusion measurements at 3.0 T are feasible and directly benefit from the
      inherently higher SNR at 3.0 T. The higher SNR also translates into an increased
      SMax, whereas MTT and TTP are independent of the field strength.

PMID- 17507813
TI  - Diffusion tensor magnetic resonance imaging of prostate cancer.
AB  - PURPOSE: To explore the feasibility of 3T magnetic resonance (MR) diffusion
      tensor imaging (DTI) and fiber tracking (FT) in patients with prostate cancer.
      MATERIALS AND METHODS: Thirty consecutive patients (mean age, 62.5 years) with
      biopsy proven prostate cancer underwent 3T-MR imaging (MRI) and DTI using a 6
      channel external phased-array coil before radical prostatectomy. Regions of
      interest of 14 pixels were defined in tumors and nonaffected areas in the
      peripheral zone (PZ) and central gland (CG), according to histopatology after
      radical prostatectomy. Apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA) values were determined. Differences in mean ADC and FA values
      among prostate cancer, normal PZ and CG were compared by 2-sided Student t test.
      The predominant diffusion direction of the prostate anisotropy was color coded on
      a directionally encoded color (DEC) map. A 3D reconstruction of fiber tract
      orientations of the whole prostate was determined using the continuous tracking
      method. The overall image quality for tumor localization and local staging was
      assessed in retrospective matching with whole-mount section histopathology
      images. Nodules detected at MRI were classified as matched lesions if tumor
      presence and extension were evidenced at histopathology. RESULTS: For all the
      patients, the DTI sequence images were suitable for the evaluation of the zonal
      anatomy of the prostate gland and the tumor localization. Quantitative evaluation
      of the regions of interest (ROIs) showed a mean ADC value significantly lower in
      the peripheral neoplastic area (1.06 +/- 0.37 x 10(-3) mm2/s) than in the normal
      peripheral portion (1.95 +/- 0.38 x 10(-3) mm2/s) (P < 0.05). The mean FA values
      calculated in the normal peripheral (0.47 +/- 0.04) and central area (0.41 +/-
      0.08) were very similar (P > 0.05). The mean FA values in the neoplastic lesion
      (0.27 +/- 0.05) were significantly lower (P < 0.05) than in the normal peripheral
      area and in the normal central and adenomyomatous area. DEC map showed a top
      bottom type preferential direction in the peripheral but not in the central area,
      with the tumor lesions reducing the diffusion coding direction represented as
      color zones tending toward gray. Tractographic analysis permitted good
      delineation of the prostate anatomy (capsule outline, peripheral and central area
      borders) and neoplastic lesion extension and capsule infiltration compared with
      histopathology. CONCLUSIONS: Three Tesla DTI of the prostate gland is feasible
      and has the potential for providing improved diagnostic information.

PMID- 17507814
TI  - Prostate and lymph node proton magnetic resonance (MR) spectroscopic imaging with
      external array coils at 3 T to detect recurrent prostate cancer after radiation
      therapy.
AB  - In a patient suspected of having recurrent prostate cancer after radiation
      therapy, we demonstrate the feasibility of noninvasive proton magnetic resonance
      spectroscopic (1H-MRS) imaging of the prostate and a lymph node at 3 T using a
      matrix of external surface coils. Written informed consent was obtained from the
      patient. With 1H-MRS imaging, high choline with low citrate signal was observed
      in the prostate, and in the lymph node a signal of choline-containing compounds
      was identified. The tissue level of the compounds in the enlarged lymph node was
      estimated to be 8.1 mmol/kg water. Subsequent histopathological analysis of
      systematic transrectal ultrasound-guided prostate biopsy and computed tomography
      guided biopsy of the lymph node confirmed the presence of prostate cancer in
      both.

PMID- 17507815
TI  - High-resolution magnetic resonance imaging of the temporomandibular joint: image
      quality at 1.5 and 3.0 Tesla in volunteers.
AB  - PURPOSE: To assess the image quality of a high-resolution imaging protocol for
      the temporomandibular joint (TMJ) at 3.0 T and to compare it with our standard
      1.5 T protocol. MATERIALS AND METHODS: Fifteen volunteers without history of TMJ
      dysfunction underwent bilateral magnetic resonance imaging (MRI) of the TMJ with
      the jaw in closed and open position. MRI was performed with using a 1.5 T
      (standard TMJ coil) and 3.0 T (purpose build phased array coil) MR system
      (Gyroscan Intera 1.5 T and 3.0 T; Philips Medical Systems, Best, the
      Netherlands). Imaging protocols consisted of a parasagittal PDw-TSE sequence and
      a coronal PDw-TSE sequence in closed mouth position and a sagittal PDw-TSE
      sequence in open mouth position. Acquisition parameters were adjusted for 3.0 T
      and voxel size was reduced from 0.29 x 0.29 x 3.0 mm (1.5 T) to 0.15 x 0.15 x 1.5
      mm (3.0 T). Total examination time (15 minutes) was similar for both systems. Two
      observers assessed in consensus delineation, image quality, and artifacts of
      anatomic landmarks (disk, bilaminar zone, capsular attachment, cortical bone) and
      ranked them qualitatively on a 5-point scale from 1 (optimal) to 5
      (nondiagnostic). Disk position and motility was noted. For CNR analysis, signal
      intensity from disk and retrodiscal tissue was measured. RESULTS: Disk position
      and mobility was identical at both field strengths. All anatomic landmarks were
      visualized significantly better at 3.0 T. In particular, the capsular attachment
      was depicted in more detail. Overall image quality was ranked significantly
      higher at 3.0 T, whereas artifact score was similar. Quantitative evaluation
      showed significantly higher CNR for 3.0 T (10.23 vs. 8.08, P < 0.0001).
      CONCLUSION: Depiction of the normal anatomy of the TMJ benefits significantly
      when investing the higher SNR at 3.0 T into better spatial resolution. We
      anticipate that this advantage of 3.0 T MRI will also permit a more detailed
      analysis of capsular and disk pathology.

PMID- 17507816
TI  - Finger A2 pulley lesions in rock climbers: detection and characterization with
      magnetic resonance imaging at 3 Tesla--initial results.
AB  - OBJECTIVES: To evaluate magnetic resonance imaging (MRI) at 3 T in the diagnosis
      and characterization of lesions of the finger flexor A2 pulley in patients with
      clinically suspected A2 pulley lesions. MATERIALS AND METHODS: Eight consecutive
      patients with clinically suspected lesions of the A2 pulley were included in this
      retrospective study. 3 T MRI was performed with T1-weighted, T2-weighted fat
      suppressed, and T1-weighted fat suppressed contrast enhanced sequences. The A2
      pulley of all the fingers visible on the images were analyzed and pulley lesions
      characterized. RESULTS: All asymptomatic pulleys were normal at MRI. In the 8
      symptomatic fingers 7 pulleys were abnormal at MRI. With the clinical examination
      as gold standard, sensitivity, specificity, positive predictive value, and
      negative predictive value of MRI were 87.5%, 100%, 100%, and 95.2% respectively.
      Characterization of the different pulley lesion was possible. CONCLUSION: MRI at
      3 T allows reliable direct visualization and characterization of traumatic A2
      pulley lesions.

PMID- 17507818
TI  - High-resolution whole-body magnetic resonance imaging applications at 1.5 and 3
      Tesla: a comparative study.
AB  - OBJECTIVES: To analyze the impact of altered magnetic field properties on image
      quality and on potential artifacts when an established whole-body magnetic
      resonance imaging (WB-MRI) protocol at 1.5 Tesla (T) is migrated to 3 T.
      MATERIALS AND METHODS: Fifteen volunteers underwent noncontrast magnetic
      resonance imaging (MRI) on 32-channel whole body-scanners at 1.5 and 3 T with the
      use of parallel acquisition techniques (PAT). Coronal T1-weighted TSE- and short
      tau inversion recovery (STIR)-sequences at 4 body levels including sagittal
      imaging of the whole spine were performed. Additional axial HASTE-imaging of lung
      and abdomen, T1-/T2-weighted-TSE- and EPI-sequences of the brain and T2-weighted
      respiratory-triggered imaging of the liver was acquired. Both data sets were
      compared by 2 independent readers in respect to artifacts and image quality using
      a 5-point scale. Regions of pronounced artifacts were defined. RESULTS: Overall
      image impression was both qualitatively rated as "good" at 1.5 and 3 T for T1-w
      TSE- and STIR-imaging of the whole body and spine. At 1.5 T, significantly better
      quantitative values for overall image quality were found for WB-STIR, T2-w-TSE
      imaging of the liver and brain (Wilcoxon Mann-Whitney U Test; P < 0.05), overall
      rated as good at 3 T. Significantly higher dielectric effects at 3 T were
      affecting T1-w- and STIR-WB-MRI, and HASTE of the abdomen and better image
      homogeneity at 1.5 T was observed for T1-weighted-/STIR-WB-MRI and T1-w-TSE
      imaging of the spine. Pulsation artifacts were significantly increased at 3 T for
      T1-w WB-MRI. Significantly higher susceptibility artifacts were found for GRE
      sequences of the brain at 3 T. Motion artifacts, Gibbs-Ringing, and image
      distortion was not significantly different and showed slightly higher
      quantitative values at 3 T (except for HASTE imaging of the abdomen). Overall
      scan time was 45 minutes and 44 seconds at 1.5 T and 40 minutes and 28 seconds at
      3 T at identical image resolution. CONCLUSION: Three Tesla WB-MRI is feasible
      with good image quality comparable to 1.5 T. 3.0 T WB-MRI shows significantly
      more artifacts with a mild to moderate impact on image assessment. Therefore 1.5
      T WB-MRI is the preferred image modality. Overall scan time at 3 T is reduced
      with the use of parallel imaging at a constant image resolution.

PMID- 17507817
TI  - Quantitative T2 mapping of matrix-associated autologous chondrocyte
      transplantation at 3 Tesla: an in vivo cross-sectional study.
AB  - OBJECTIVES: To evaluate magnetic resonance (MR) T2 mapping for characterization
      of cartilage repair tissue following matrix-associated autologous cartilage
      transplantation (MACT). MATERIALS AND METHODS: Fifteen patients were evaluated
      following MACT using a 3T MR scanner. Patients were categorized into 2
      postoperative intervals: I: 3-13 months, II: 19-42 months. Mean T2 relaxation
      times calculated from multiple spin-echo sequence were determined in regions of
      interest (MACT and normal hyaline cartilage) and T2 line profiles through the
      repair tissue and control sites were acquired. RESULTS: Mean global T2 values of
      repair tissue in group I were significantly higher than at control sites (P <
      0.05). Repair tissue in group II showed no significant difference to control
      sites. Repair tissue T2 line profiles normalized over time toward the control
      sites. CONCLUSIONS: T2 mapping allows visualization of cartilage repair tissue
      maturation. Global T2 repair tissue values approach that of control sites after
      more than 1.5 years, similar behavior is seen in the zonal organization.

PMID- 17507819
TI  - High-resolution magnetic resonance imaging (MRI) at 3.0 Tesla in the short-term
      follow-up of patients with proven cervical artery dissection.
AB  - PURPOSE: For the imaging evaluation of patients with suspected cervical artery
      dissection (CAD) in the last decade, magnetic resonance imaging (MRI) has become
      the first line imaging modality. However, CAD is a highly dynamic process with
      rapid changes over time. Aim of this study was to assess the short-term
      morphologic changes in patients with proven CAD by MRI within 2 weeks after the
      initial diagnosis using a multicontrast high-resolution noninvasive vessel wall
      imaging approach at 3.0 T. MATERIALS AND METHODS: Eighty-two patients with
      clinically suspected CAD were examined using a 3.0 T system (Gyroscan Intera,
      Philips). Imaging protocol consisted of 3-dimensional inflow MRA (repetition time
      [TR]/echo time [TE]/flip angle [FA] = 25 milliseconds/3.1 milliseconds/16
      degrees, reconstructed voxel size 0.3 x 0.3 x 0.8 mm), black blood T1w 3
      dimensional spoiled gradient echo (TR/TE/FA = 31 milliseconds/7.7 milliseconds/15
      degrees, 0.3 x 0.3 x 1.0 mm), and fat suppressed T2w turbo spin echo (TSE)
      (TR/TE/echo train length = 3 heart beats/44 milliseconds/7, 0.3 x 0.3 x 2 mm).
      Three observers in consensus performed image analysis. Images were assessed with
      regard to presence and size of intramural hematoma, degree of stenosis, presence
      of intraluminal thrombus, development of pseudoaneurysm, and incidence of
      additional dissections. In 29 patients (35%) a dissection had initially been
      proven by direct visualization of an intramural hematoma. Twenty-one patients
      (72%; 7 male, 14 female; mean age 41.5 years) were available for follow-up
      studies leading to a total of 24 diseased cervical arteries being reevaluated 2
      weeks later for prospective follow-up. RESULTS: Mean interval between initial
      study and follow-up was 14.2 days (range 7-30 days). Eighteen patients had
      presented with an acute CAD in 1 artery, 3 patients with an acute CAD in 2
      arteries. At follow-up, degree of stenosis had increased in 2 arteries, remained
      unchanged in 13, and decreased in 5 arteries. Four initially occluded arteries
      were recanalized at follow-up. In 3 arteries a pseudoaneurysm had been visible in
      the initial study and remained unchanged at follow-up; in 1 artery a new
      pseudoaneurysm was observed. In 3 arteries, new dissections were identified
      during follow-up. CONCLUSION: High-resolution MRI of acute CAD at 3.0 T permits a
      refined cross-sectional and longitudinal analysis of the morphologic features of
      CAD. The increased signal-to-noise ratio at 3.0 T allows for a high spatial
      resolution permitting detailed analysis of the diseased vessel segment. An
      unequivocal distinction between intramural hematoma and thrombus was possible.
      Information could be gained with regard to recanalization, degree of stenosis,
      formation of pseudoaneurysm, and appearance of new dissections making short-term
      follow-up in pts with acute CAD recommendable. Further studies are needed to
      assess the relationship between short-term results and definite outcome.

PMID- 17507820
TI  - Magnetic resonance angiography in infrapopliteal arterial disease: prospective
      comparison of 1.5 and 3 Tesla magnetic resonance imaging.
AB  - PURPOSE: To prospectively determine the accuracy of 1.5 Tesla (T) and 3 T
      magnetic resonance angiography (MRA) versus digital subtraction angiography (DSA)
      in the depiction of infrageniculate arteries in patients with symptomatic
      peripheral arterial disease. PATIENTS AND METHODS: A prospective 1.5 T, 3 T MRA,
      and DSA comparison was used to evaluate 360 vessel segments in 10 patients (15
      limbs) with chronic symptomatic peripheral arterial disease. Selective DSA was
      performed within 30 days before both MRAs. The accuracy of 1.5 T and 3 T MRA was
      compared with DSA as the standard of reference by consensus agreement of 2
      experienced readers. Signal-to-noise ratios (SNR) and signal-difference-to-noise
      ratios (SDNRs) were quantified. RESULTS: No significant difference in overall
      image quality, sufficiency for diagnosis, depiction of arterial anatomy, motion
      artifacts, and venous overlap was found comparing 1.5 T with 3 T MRA (P > 0.05 by
      Wilcoxon signed rank and as by Cohen k test). Overall sensitivity of 1.5 and 3 T
      MRA for detection of significant arterial stenosis was 79% and 82%, and
      specificity was 87% and 87% for both modalities, respectively. Interobserver
      agreement was excellent k > 0.8, P < 0.05) for 1.5 T as well as for 3 T MRA. SNR
      and SDNR were significantly increased using the 3 T system (average increase:
      36.5%, P < 0.032 by t test, and 38.5%, P < 0.037 respectively). CONCLUSIONS:
      Despite marked improvement of SDNR, 3 T MRA does not yet provide a significantly
      higher accuracy in diagnostic imaging of atherosclerotic lesions below the knee
      joint as compared with 1.5 T MRA.

PMID- 17507821
TI  - High-resolution magnetic resonance angiography of the lower extremities with a
      dedicated 36-element matrix coil at 3 Tesla.
AB  - INTRODUCTION: Recent developments in hard- and software help to significantly
      increase image quality of magnetic resonance angiography (MRA). Parallel
      acquisition techniques (PAT) help to increase spatial resolution and to decrease
      acquisition time but also suffer from a decrease in signal-to-noise ratio (SNR).
      The movement to higher field strength and the use of dedicated angiography coils
      can further increase spatial resolution while decreasing acquisition times at the
      same SNR as it is known from contemporary exams. The goal of our study was to
      compare the image quality of MRA datasets acquired with a standard matrix coil in
      comparison to MRA datasets acquired with a dedicated peripheral angio matrix coil
      and higher factors of parallel imaging. MATERIALS AND METHODS: Before the first
      volunteer examination, unaccelerated phantom measurements were performed with the
      different coils. After institutional review board approval, 15 healthy volunteers
      underwent MRA of the lower extremity on a 32 channel 3.0 Tesla MR System. In 5 of
      them MRA of the calves was performed with a PAT acceleration factor of 2 and a
      standard body-matrix surface coil placed at the legs. Ten volunteers underwent
      MRA of the calves with a dedicated 36-element angiography matrix coil: 5 with a
      PAT acceleration of 3 and 5 with a PAT acceleration factor of 4, respectively.
      The acquired volume and acquisition time was approximately the same in all
      examinations, only the spatial resolution was increased with the acceleration
      factor. The acquisition time per voxel was calculated. Image quality was rated
      independently by 2 readers in terms of vessel conspicuity, venous overlay, and
      occurrence of artifacts. The inter-reader agreement was calculated by the kappa
      statistics. SNR and contrast-to-noise ratios from the different examinations were
      evaluated. RESULTS: All 15 volunteers completed the examination, no adverse
      events occurred. None of the examinations showed venous overlay; 70% of the
      examinations showed an excellent vessel conspicuity, whereas in 50% of the
      examinations artifacts occurred. All of these artifacts were judged as none
      disturbing. Inter-reader agreement was good with kappa values ranging between
      0.65 and 0.74. SNR and contrast-to-noise ratios did not show significant
      differences. CONCLUSION: Implementation of a dedicated coil for peripheral MRA at
      3.0 Tesla helps to increase spatial resolution and to decrease acquisition time
      while the image quality could be kept equal. Venous overlay can be effectively
      avoided despite the use of high-resolution scans.

PMID- 17507822
TI  - Extracorporeal life support to terminate refractory ventricular tachycardia.
AB  - OBJECTIVE: Extracorporeal life support (ECLS) has been applied successfully to
      patients with cardiopulmonary failure in extreme situations. Refractory
      ventricular tachycardia has high mortality and morbidity rates if not terminated
      in time. This study describes our preliminary experiences in using ECLS to treat
      patients with refractory ventricular tachycardia. DESIGN: Retrospective chart
      review. SETTING: Hospital. PATIENTS: Eleven patients suffering from ventricular
      tachycardia refractory to antiarrhythmia agents and cardioversion attempts.
      INTERVENTIONS: From January 2002 to December 2004, 11 patients suffering from
      ventricular tachycardia refractory to antiarrhythmia agents and cardioversion
      attempts were treated with ECLS. Mean patient age was 31 +/- 21 yrs (range, 3-69
      yrs). The triggering events were acute myocarditis (n = 8), coronary artery spasm
      (n = 1), and hypoxemia secondary to acute respiratory distress syndrome (n = 2).
      Nine (82%) patients received venoarterial mode support and the remaining two
      (18%) were supported with venovenous mode to correct hypoxemia. Pump flow was
      first maximized (mean, 3800 +/- 1100 mL/min) to unload the heart, and an intra
      aortic balloon pump was used to deal with the increased afterload (n = 8).
      MEASUREMENTS AND MAIN RESULTS: Mean ventricular tachycardia duration before ECLS
      was 50 +/- 16 mins (range, 20-75 mins) and soon converted to a sinus rhythm
      following ECLS deployment, including four patients who experienced spontaneous
      recovery without attempted cardioversion, in a mean of 7.4 mins (range, 1-20
      mins). Four patients required temporary pacing but none needed a permanent
      pacemaker after recovery. Mean duration of ECLS support was 119 +/- 69 hrs
      (range, 12-250 hrs). We excluded one patient who had permanent brain injury and
      another who succumbed to multiple organ failure. Nine (82%) patients were weaned
      and discharged with normal cardiac function. No recurrent ventricular tachycardia
      attack but one recurrent cardiomyopathy (ejection fraction = 15%) was reported
      during a mean 42-month follow-up. CONCLUSIONS: Using ECLS to terminate refractory
      ventricular tachycardia proved effective for selected patients when conventional
      therapeutic options were exhausted. Early deployment of ECLS to prevent secondary
      organ injury, maintain sufficient cardiac unloading, and avoid complications
      during ECLS support was central to successful outcomes.

PMID- 17507823
TI  - Effects of controlled perioperative antimicrobial prophylaxis on infectious
      outcomes in pediatric cardiac surgery.
AB  - OBJECTIVES: To examine the efficacy of a protocol for the prophylactic use of
      antimicrobials in pediatric cardiac surgery. DESIGN: Nonrandomized comparison of
      two groups of patients studied sequentially. SETTING: Pediatric intensive care
      unit of university hospital. PATIENTS: Infants and children <18 yrs of age who
      had undergone cardiac surgery. INTERVENTIONS: Limitation of prophylactic
      antimicrobials to <48 hrs after operation and, in patients at high risk of
      methicillin-resistant Staphylococcus aureus, strong recommendation to use
      glycopeptides. MEASUREMENTS AND MAIN RESULTS: No intervention was applied in 189
      patients (control group) during the first 21 months, whereas the intervention was
      applied in 185 patients (intervention group) during the next 18 months. In the
      intervention group, prophylaxis was recommended to be discontinued <48 hrs
      postoperatively. As a result, antimicrobials were administered for a median of 4
      days (range 2-14) in the intervention group, significantly shorter than 7 days (3
      35) in controls. This was associated with a trend toward a lower frequency of
      postoperative infections, including at the surgical site, and with significantly
      lower costs of antimicrobial therapy and a significantly lower rate of newly
      acquired nasal colonization with antibiotic-resistant pathogens in the
      intervention group (8%) than in controls (17%).Since, in the intervention group,
      glycopeptides were strongly recommended for patients at high risk of methicillin
      resistant S. aureus, the frequency of surgical-site infections (0% vs. 18%) and
      the frequency of all infections (11% vs. 39%) were significantly lower in the
      intervention group than in the control group. CONCLUSIONS: Limiting the duration
      of prophylactic antimicrobials was cost-effective and reduced the risk of
      acquiring resistant pathogens without increasing the frequency of postoperative
      infections. The use of glycopeptides in properly selected patients at high risk
      of methicillin-resistant S. aureus infection can lower the risk of postoperative
      infections.

PMID- 17507824
TI  - Toward the prevention of acute lung injury: protocol-guided limitation of large
      tidal volume ventilation and inappropriate transfusion.
AB  - OBJECTIVE: We evaluated the effect of two quality improvement interventions (low
      tidal volume ventilation and restrictive transfusion) on the development of acute
      lung injury in mechanically ventilated patients. DESIGN: Observational cohort
      study. SETTING: Three intensive care units in a tertiary academic center.
      PATIENTS: We included patients who were mechanically ventilated for > or =48 hrs
      excluding those who refused research authorization or had preexisting acute lung
      injury or pneumonectomy. INTERVENTIONS: Multifaceted interdisciplinary
      intervention consisting of Web-based teaching, respiratory therapy protocol, and
      decision support within computerized order entry. MEASUREMENTS AND MAIN RESULTS:
      Of 375 patients who met the inclusion and exclusion criteria, 212 were ventilated
      before and 163 after the interventions. Baseline characteristics were similar
      between the two groups except for a lower frequency of sepsis (27% vs. 17%, p =
      .030), trend toward lower median glucose level (140 mg/dL, interquartile range
      118-168 vs. 132 mg/dL, interquartile range 113-156, p = .096), and lower
      frequency of pneumonia (27% vs. 20%, p = .130) during the second period. We
      observed a large decrease in tidal volume (10.6-7.7 mL/kg predicted body weight,
      p < .001), in peak airway pressure (31-25 cm H2O, p < .001), and in the
      percentage of transfused patients (63% to 38%, p < .001) after the intervention.
      The frequency of acute lung injury decreased from 28% to 10% (p < .001). The
      duration of mechanical ventilation decreased from a median of 5 (interquartile
      range 4-9) to 4 (interquartile range 4-8) days (p = .030). When adjusted for
      baseline characteristics in a multivariate logistic regression analysis, protocol
      intervention was associated with a reduction in the frequency of new acute lung
      injury (odds ratio 0.21, 95% confidence interval 0.10-0.40). CONCLUSIONS:
      Interdisciplinary intervention effectively decreased large tidal volumes and
      unnecessary transfusion in mechanically ventilated patients and was associated
      with a decreased frequency of new acute lung injury.

PMID- 17507825
TI  - Residents feel unprepared and unsupervised as leaders of cardiac arrest teams in
      teaching hospitals: a survey of internal medicine residents.
AB  - OBJECTIVE: We aimed to determine internal medicine residents' perceptions of the
      adequacy of their training to serve as in-hospital cardiac arrest team leaders,
      given the responsibility of managing acutely critically ill patients and with
      recent evidence suggesting that the quality of cardiopulmonary resuscitation
      provided in teaching hospitals is suboptimal. DESIGN: Cross-sectional postal
      survey. SETTING: Canadian internal medicine training programs. PARTICIPANTS:
      Internal medicine residents attending Canadian English-speaking medical schools.
      INTERVENTIONS: A survey was mailed to internal medicine residents asking
      questions relating to four domains: adequacy of training, perception of
      preparedness, adequacy of supervision and feedback, and effectiveness of
      additional training tools. MEASUREMENTS AND MAIN RESULTS: Of the 654 residents
      who were sent the survey, 289 residents (44.2%) responded. Almost half of the
      respondents (49.3%) felt inadequately trained to lead cardiac arrest teams. Many
      (50.9%) felt that the advanced cardiac life support course did not provide the
      necessary training for team leadership. A substantial number of respondents (40%)
      reported receiving no additional cardiac arrest training beyond the advanced
      cardiac life support course. Only 52.1% of respondents felt prepared to lead a
      cardiac arrest team, with 55.3% worrying that they made errors. Few respondents
      reported receiving supervision during weekdays (14.2%) or evenings and weekends
      (1.4%). Very few respondents reported receiving postevent debriefing (5.9%) or
      any performance feedback (1.3%). Level of training and receiving performance
      feedback were associated with perception of adequacy of training (r(2) = .085, p
      < .001). Respondents felt that additional training involving full-scale
      simulation, leadership skills training, and postevent debriefing would be most
      effective in increasing their skills and confidence. CONCLUSIONS: The results
      suggest that residents perceive deficits in their training and supervision to
      care for critically ill patients as cardiac arrest team leaders. This raises
      sufficient concern to prompt teaching hospitals and medical schools to consider
      including more appropriate supervision, feedback, and further education for
      residents in their role as cardiac arrest team leaders.

PMID- 17507826
TI  - PF4 ENHANCED assay for the diagnosis of heparin-induced thrombocytopenia in
      complex medical and surgical patients.
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of the PF4 ENHANCED (GTI
      Diagnostics, Waukesha, WI) enzyme-linked immunosorbent assay for heparin-induced
      thrombocytopenia using the carbon-14 serotonin-release assay as the reference
      method. DESIGN: A total of 34 patients were prospectively enrolled with a variety
      of diagnoses and suspected heparin-induced thrombocytopenia. They were clinically
      scored and underwent testing with the (14)C-serotonin-release assay. Enzyme
      linked immunosorbent assay and (14)C-serotonin-release assay results were also
      available from 21 medical and surgical patients who had previously been tested.
      MAIN RESULTS: With the (14)C-serotonin-release assay as the reference method, the
      sensitivity and specificity of the enzyme-linked immunosorbent assay were 93% and
      65%, respectively. There was only one false-negative enzyme-linked immunosorbent
      assay. The clinical scores were frequently misleading, largely because of
      difficulty excluding other causes of thrombocytopenia. CONCLUSION: Because of its
      high sensitivity, we believe the PF4 ENHANCED enzyme-linked immunosorbent assay
      should be used to identify heparin-induced thrombocytopenia in patients with
      multiple potential causes of thrombocytopenia, although false-positive results
      will not be uncommon.

PMID- 17507827
TI  - Cochlear implantation in Children with CHARGE syndrome: therapeutic decisions and
      outcomes.
AB  - OBJECTIVES: Ear anomalies and deafness are associated with CHARGE syndrome, which
      also presents with a cluster of features including coloboma of the eye, heart
      defects, atresia of the choanae, developmental retardation, and genitourinary
      abnormalities. The aim of this study is to explore the viability of cochlear
      implantation in children with CHARGE syndrome and to assess the outcome. STUDY
      DESIGN: Retrospective chart review. METHODS: Eleven children presenting with
      severe to profound sensorineural hearing loss associated with CHARGE syndrome
      were the subjects of this study. Routine audiometric measurements and the Infant
      Toddler Meaningful Auditory Integration Scale (IT-MAIS) were performed pre- and
      postoperatively. In addition, the degree of the subjects' cochlear deformity were
      measured and correlated to outcome. RESULTS: All patients had varying degrees of
      ear anomalies, seven patients suffered from coloboma of the eyes, two had heart
      defects, five exhibited choanal atresia, eleven showed developmental retardation,
      and six had genitourinary abnormalities. Ten of the children underwent cochlear
      implantation with complete insertion of the electrode array without complication
      and were followed over a 3-month to a 7-year period. The eleventh child was not
      implanted because of severe retardation. All of the implanted children showed
      varying, but limited degrees, of auditory benefit as measured by routine
      audiometry and the IT-MAIS. CONCLUSIONS: Careful treatment planning for children
      with sensorineural hearing loss and CHARGE syndrome can lead to varying, but
      limited degrees, of auditory benefit with no increase in surgical complications.
      Although the implant enhanced the children's 'connectivity' to the environment,
      it did not promote the development of oral language skills in this population.

PMID- 17507828
TI  - A novel drug therapy for recurrent laryngeal nerve injury using T-588.
AB  - OBJECTIVES/HYPOTHESIS: We have previously shown that gene therapy using Insulin
      like growth factor (IGF)-I, glial cell line-derived neurotrophic factor (GDNF),
      and brain-derived neurotrophic factor (BDNF), or a combination of these trophic
      factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy.
      However, there remain some difficulties preventing this option from becoming a
      common clinical therapy for RLN injury. Thus, we need to develop novel treatment
      option that overcomes the problems of gene therapy.R(-)-1-(benzothiophen-5-yl)-2
      [2-N,N-diethylamino]ethoxy]ethanol hydrochloride (T-588), a synthetic compound,
      is known to have neuroprotective effects on neural cells. In the present study,
      the possibility of new drug treatments using T-588 for RLN injury was assessed
      using rat models. STUDY DESIGN: Animal study. METHODS: Animals were administered
      T-588 for 4 weeks. The neuroprotective effects of T-588 administration after
      vagal nerve avulsion and neurofunctional recovery after recurrent laryngeal nerve
      crush were studied using motoneuron cell counting, evaluation of choline
      acetyltransferase immunoreactivity, the electrophysiologic examination, and the
      re-mobilization of the vocal fold. RESULTS: T-588 administration successfully
      prevented motoneuron loss and ameliorated the choline acetyltransferase
      immunoreactivity in the ipsilateral nucleus ambiguus after vagal nerve avulsion.
      Significant improvements of motor nerve conduction velocity of the RLN and vocal
      fold movement were observed in the treatment group when compared to controls.
      CONCLUSION: These results indicate that oral administration of T-588 might be a
      promising therapeutic option in treating peripheral nerve injury.

PMID- 17507829
TI  - Surfactant protein B detection and gene expression in chronic rhinosinusitis.
AB  - INTRODUCTION: Surfactant protein (SP)-B is a hydrophobic protein secreted within
      pulmonary surfactant that facilitates the adsorption of surface-active lipids to
      the air-liquid interface of the alveoli and increases alveolar stability. SP-B
      may also have anti-inflammatory properties. It is implicated in decreasing the
      pulmonary inflammatory response to bacterial lipopolysaccharide. However, the
      expression and function of SP-B in the sinonasal cavities has not been
      elucidated. Our objective was to detect the presence of SP-B, measure alterations
      in several forms of chronic rhinosinusitis (CRS), and localize cellular protein
      expression. MATERIALS/METHODS: Sinus mucosal biopsies were performed in patients
      with allergic fungal rhinosinusitis (AFRS), nonatopic CRS with nasal polyposis
      (NP), and cystic fibrosis (CF) and in healthy controls. SP-B mRNA was measured in
      CRS and control patients using quantitative polymerase chain reaction. Immunoblot
      analysis and immunolocalization of SP-B were also performed. RESULTS: CF (n = 4)
      showed significantly increased levels of SP-B (169-fold) mRNA (P = .004) when
      compared with controls (n = 5). CRS with NP (n = 5) and AFRS (n = 7) also
      demonstrated elevated levels of SP- B (14-fold and 4-fold, respectively) when
      compared with the control group, although these were not statistically
      significant. Immunoblot analysis confirmed the presence of the translated
      product, and immunolocalization revealed expression in the epithelium and
      submucosal glandular elements. CONCLUSION: This is the first study to detect and
      characterize SP-B in human sinus mucosa. Furthermore, SP-B is significantly up
      regulated in CF CRS.

PMID- 17507830
TI  - Tissue-engineered bone formation with gene transfer and mesenchymal stem cells in
      a minimally invasive technique.
AB  - BACKGROUND: The objective of this study was to use a chitosan-alginate gel to
      implant bone marrow-derived mesenchymal stem cells subcutaneously in a minimally
      invasive manner and promote bone formation by the simultaneously transferred
      osteogenic protein (OP)-1 (bone morphogenic protein-7) gene. METHOD AND RESULTS:
      The complex of polyethylenimine/luciferase plasmid DNA embedded in the gel was
      able to transfect HEK 293 cells on a culture dish or co-encapsulated in the gel.
      When injected into the subcutaneous space of mice, luciferase expression was two
      to three orders of magnitude increased above the background. To examine the
      efficacy of gene-, cell-, and combined gene- and cell-encapsulated gels in tissue
      generation, samples were injected into the subcutaneous space of 6-week-old
      athymic nude mice, and the OP-1 plasmid was studied. At 8 weeks after the
      injection, the gels only maintained their volumetric shape when human mesenchymal
      stem cells (hMSCs) were encapsulated, but otherwise the gels were partially
      dissolved. Transgene expression of OP-1 was clearly detected in the samples after
      4 weeks but not after 8 weeks. Type II collagen was detected in all the gels
      containing the OP-1 plasmid, with or without hMSCs. The samples with the
      combination of OP-1 DNA and hMSCs revealed strong type II collagen expression as
      well as osteoid foci. CONCLUSION: These results suggest that combined gene and
      hMSC delivery within a chitosan-alginate gel could be an interesting approach for
      tissue engineering.

PMID- 17507831
TI  - Isoflavones and cardiovascular risk in postmenopausal women: no free lunch.

PMID- 17507832
TI  - Symptoms, menopause status, and country differences: a comparative analysis from
      DAMES.
AB  - OBJECTIVE: To investigate reported frequencies of menopausal symptoms among women
      in four countries, namely Lebanon, Morocco, Spain, and the United States, and to
      assess the relative role of menopause status, country of residence, and other
      factors in explaining differences in symptomatology. DESIGN: Surveys of
      representative samples of approximately 300 women aged 45 to 55 years in each
      site were conducted, using an instrument that includes demographic, health, and
      menopausal variables, in addition to perceptions and attitudes toward menopause.
      Statistical and textual analyses are used to examine differentials and the
      factors that influence them. RESULTS: The burden of symptoms and the frequencies
      of symptoms differ across sites, but hot flashes are reported everywhere by just
      under one half of the respondents. The most frequent symptoms are joint pain,
      fatigue, impatience/nervousness, sleep disturbances, memory loss, and one or more
      emotional symptoms. Menopause status is significantly associated with hot flashes
      and vasomotor symptoms and to a lesser extent with emotional and sexual symptoms.
      Smoking, schooling, employment, and age are also associated with the frequency of
      selected symptoms. Country of residence influences reported symptoms over and
      above other factors. CONCLUSIONS: Similarities among core symptoms and
      differences in the expression of symptoms were found across sites. Both
      biological (menopause status) and cultural (country of residence) variables
      influence symptomatology.

PMID- 17507833
TI  - A randomized, open-label, crossover study comparing the effects of oral versus
      transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal
      hormones in naturally menopausal women.
AB  - OBJECTIVE: To compare the changes induced by oral versus transdermal estrogen
      therapy on the total and free serum concentrations of testosterone (T), thyroxine
      (T4), and cortisol (C) and the concentrations of their serum binding globulins
      sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding
      globulin in naturally menopausal women. DESIGN: Randomized, open-label,
      crossover. Interventions included a 6-week withdrawal from previous hormone
      therapy (baseline), followed in randomized order by 12 weeks of oral conjugated
      equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2)
      (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously
      during both transdermal estrogen therapy regimens. RESULTS: Twenty-seven women
      were enrolled in the study, and 25 completed both treatment periods. The mean(SD)
      percentage changes from baseline of sex hormone-binding globulin, total T, and
      free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%),
      respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2.
      The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and
      free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%),
      respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2.
      The mean (SD) percentage changes of cortisol-binding globulin, total C, and free
      C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%),
      respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2.
      Concentrations of all hormones and binding globulins were significantly different
      (P < or = 0.003) during administration of oral versus transdermal estrogen
      therapy, except for free T4 and free C. CONCLUSIONS: Compared with oral CEE, TD
      E2 exerts minimal effects on the total and free concentrations of T, T4, and C
      and their binding proteins.

PMID- 17507834
TI  - Identification of novel risks for nonulcerative sexually transmitted infections
      among young men in Kisumu, Kenya.
AB  - OBJECTIVES: STI prevention interventions often aim to reduce HIV incidence.
      Understanding STI risks may lead to more effective HIV prevention. GOAL: To
      identify STI risks among men aged 18-24 in Kisumu, Kenya. STUDY DESIGN: We
      analyzed baseline data from a randomized trial of male circumcision. Participants
      were interviewed for sociodemographic and behavioral risks. Neisseria gonorrhoeae
      (NG) and Chlamydia trachomatis (CT) were diagnosed by polymerase chain reaction
      assay and Trichomonas vaginalis (TV) by culture. The outcome for logistic
      regression analysis was infection with NG, CT, or TV. RESULTS: Among 2743 men,
      214 (7.8%; 95% CI: 6.8%-8.8%) were infected with any STI. In multivariable
      analysis, statistically significant risks for infection were: living one's whole
      life in Kisumu (OR = 1.50; 95% CI: 1.12-2.01), preferring "dry" sex (OR = 1.47;
      95% CI: 1.05-2.07), HSV-2 seropositivity (OR = 1.37; 95% CI: 1.01-1.86), and
      inability to ejaculate during sex (OR = 2.04; 95% CI: 1.15-3.62). Risk decreased
      with increasing age and education, and cleaning one's penis less than 1 hour
      after sex (OR = 0.51; 95% CI: 0.33-0.80). CONCLUSION: Understanding how
      postcoital cleaning, "dry" sex, and sexual dysfunction relate to STI acquisition
      may improve STI and HIV prevention.

PMID- 17507835
TI  - Personal, relational, and peer-level risk factors for laboratory confirmed STD
      prevalence among low-income African American adolescent females.
AB  - OBJECTIVES: To identify risk factors for laboratory confirmed sexually
      transmitted disease (STD) prevalence among low-income African American adolescent
      females living in a high-risk urban area of the Southern United States. METHODS:
      Participants were 715 African American adolescent females recruited from urban
      clinics. Data collection occurred from 2002 to 2004 and included an audio
      computer assisted self-interview lasting about 60 minutes and a self-collected
      vaginal swab for NAAT to detect Trichomonas vaginalis, Chlamydia trachomatis, and
      Neisseria gonorrhoeae. Ten personal-level risk factors were assessed as well as 8
      risk factors involving either peer or relational factors. RESULTS: Adolescents
      (28.8%) tested positive for at least 1 STD. Six personal-level and 4 social-level
      measures achieved a bivariate screening level of significance. In the
      multivariate model, only 3 measures achieved significance: gang involvement,
      social support from peers, and fear of condom use negotiation. Compared to those
      who had never belonged to a gang, those who had were about 4.2 times more likely
      (95% CI = 2.16-9.44) to test positive. Adolescents' who had higher levels of fear
      pertaining to condom use negotiation were more likely to test positive as were
      adolescents who perceived higher levels of social support from their peers.
      CONCLUSIONS: This finding suggests and supports the utility of designing
      interventions for high-risk African American adolescent females that incorporate
      objectives to modify the significant social influences related to STD
      acquisition.

PMID- 17507836
TI  - Clients of indoor commercial sex workers: heterogeneity in patronage patterns and
      implications for HIV and STI propagation through sexual networks.
AB  - OBJECTIVES: To determine whether "high-risk" clients occupied important
      sociometric positions in sexual networks of commercial sex workers and to
      estimate whether they were more likely to be HIV and STI infected. GOAL: To
      determine whether a classification of high-risk clients could be validated by
      network analysis. STUDY DESIGN: We used proxy data on clients collected from a
      cross-sectional survey of 49 indoor female sex workers. RESULTS: Two types of
      clients were categorized as high risk, including those who created sexual bridges
      between sex establishments and those who had sex with most or all the FSW at an
      establishment. High-risk clients were significantly more central and were more
      likely to be members of cohesive subgroups than were lower-risk clients. The few
      known HIV and STI infections were in high-risk clients. CONCLUSIONS: It is
      possible to identify theoretically high-risk commercial sex clients from the
      network perspective using simple data collection and categorization approaches.

PMID- 17507837
TI  - Reproductive tract infections among women attending a gynecology outpatient
      department in Vientiane, Lao PDR.
AB  - OBJECTIVES AND GOAL: To clinically and microbiologically identify reproductive
      tract infections (RTI), including sexually transmitted infections (STI), and to
      monitor the antibiotic susceptibility of Neisseria gonorrhoeae among women
      attending a gynecology outpatient department in Vientiane, Laos. STUDY DESIGN:
      Clinical and laboratory-based cross-sectional study. Women aged 15 to 49 years
      underwent a pelvic examination, and specimens were taken for laboratory testing.
      RESULTS: Of 1125 study participants, 82% clinically presented with an RTI
      syndrome. However, only 64% had an etiologically diagnosed RTI, including 11%
      with an STI. Endogenous infections were most prevalent (candidiasis 40%;
      bacterial vaginosis 25%), followed by STI [Chlamydia trachomatis 4.1%; N.
      gonorrhoeae (NG) and Trichomonas vaginalis, both 3.7%]. The 41 NG isolates showed
      20% resistance to ciprofloxacin, 98% to penicillin, and complete to tetracycline.
      CONCLUSIONS: High RTI/STI level combined with high NG resistance emphasizes that
      concurrent with syndromic case management, periodic evaluations of etiological
      diagnosis should be available to ensure adequacy of treatment algorithms and
      prescribed medications.

PMID- 17507839
TI  - [Validity and ethics of predictive allergic tests].

PMID- 17507838
TI  - Female sex workers in China: vectors of disease?
AB  - OBJECTIVE: To analyze the extent by which Chinese female sex workers (FSWs) serve
      as vectors of HIV/AIDS to an otherwise spared general population and to describe
      the implications of centering efforts solely on this high-risk group. GOAL: By
      using the example of FSWs in China, we intend to demonstrate the role that
      structural factors can have on HIV transmission above and beyond individual high
      risk behaviors. STUDY DESIGN: Literature review of years 1980-2006. RESULTS:
      Analysis of the literature suggests that major determinants of HIV transmission
      amongst FSWs in China include sociopolitical context, gender, work environment
      and finally, risky sexual behaviors. CONCLUSIONS: Chinese FSWs live in a specific
      sociopolitical context that shapes their capacities to engage in safe-sex
      practices. Focusing on FSWs as vectors of HIV/AIDS epidemic in China neglects the
      larger context that endangers all members of society and blames an already
      vulnerable population.

PMID- 17507840
TI  - [Current reasons for in-patient psoriasis management].
AB  - BACKGROUND: Currently, out-patient care is the traditional approach for the
      management of patients with psoriasis. However, some patients still require
      hospitalization. The aim of this study was to assess the main reasons for
      hospitalization of psoriasis patients. PATIENTS AND METHODS: Data are presented
      from a retrospective study performed in a single centre over a 15-year period
      (1990-2005). Hospitalizations of psoriasis patients were identified using the
      coding L 40.X from the CM10 (out-patients were excluded). For each
      hospitalization, the following details were recorded: age, sex, associated
      disorders, mean length of stay, number of re-hospitalizations, clinical type of
      psoriasis (vulgaris, pustular or erythrodermic), onset factors and treatments.
      RESULTS: One hundred and twenty-two patients corresponding to 211
      hospitalizations were included in this study. Two distinct patient populations
      could be identified. The first consisted of patients with chronic psoriasis
      vulgaris (143/211 hospitalizations, 67.8%), chiefly male (n=95, sex-ratio=1.98,
      p=0.001), alcoholic in 47/95 hospitalizations, 49.5% (p=0.004) and requiring
      frequent re-hospitalization. The second consisted of patients with acute forms of
      psoriasis, either pustular (38/211 hospitalizations, 18%) or erythrodermic
      (30/211 hospitalizations, 14.2%). Most of these patients were female (sex
      ratio=0.66) and the onset of their psoriasis was sometimes triggered by an
      infection (7/38 hospitalizations, 18% of psoriasis pustular, p=0.16) or intake of
      a new drug (6/30 hospitalizations, 20% of erythrodermic psoriasis, p=0.007).
      DISCUSSION: Hospitalization in acute care hospitals is not often used in the
      management of patients with psoriasis. Hospitalizations concern two different
      populations: the first with chronic psoriasis vulgaris and commonly associated
      disorders (alcohol abuse), and the second with acute forms of psoriasis, namely
      pustular and erythrodermic.

PMID- 17507841
TI  - [Complications after sentinel lymph node excision in patients with malignant
      melanoma].
AB  - INTRODUCTION: Side-effects occurring after sentinel lymph node excision in
      malignant melanoma patients have been poorly evaluated to date. The aim of the
      present study was to assess the side-effects of sentinel lymph node excision in
      this population. PATIENTS AND METHODS: All consecutive malignant melanoma
      patients undergoing sentinel lymph node excision between March 2000 and December
      2002 were included in this retrospective study. Patients with a metastatic
      sentinel node subsequently undergoing lymph node dissection were excluded. Median
      follow-up of patients was 12.6 +/- 8.8 months. Complications were classified as
      "early" (i.e. occurring the month following surgery), or "late" (after this
      time). RESULTS: Forty malignant melanoma patients (17 males, 23 females) with a
      normal histologic examination of their sentinel lymph node were included. They
      belonged to a series of sixty-one melanoma patients undergoing lymph node
      excision. Fourteen complications were observed in ten patients. Two early
      complications were seen: hematoma (n=1) and deep venous thrombosis with pulmonary
      embolism (n=1). Twelve late complications were observed: mild lymphoedema (n=5),
      hypertrophic scars (n=2), painful scars (n=4), and one chronic seroma (n=1). Many
      complications (33%) were observed after excision in the inguinal area.
      DISCUSSION: The complications of sentinel lymph node excision must be considered
      in determining the benefit/risk ratio of this technique.

PMID- 17507842
TI  - [Dermatological problems of musicians: a prospective study in musical students].
AB  - INTRODUCTION: Musicians are at risk of developing particular skin conditions
      related to their activity. The purpose of our work was to determine the
      frequency, describe the clinical aspects and identify the risk factors of
      specific dermatological problems in musical students. POPULATION AND METHODS: We
      carried out a prospective epidemiological study between April 2003 and April 2004
      among music students registered in four musical institutes of Tunisia. The
      musicians were questioned and examined in systematic fashion at their institutes.
      Demographic data, characteristics of instrumental practice and dermatologic
      manifestations were collected. Five hundred and ninety-four students were
      examined. The sex-ratio was 1.6 with a mean age of 22.0 +/- 4.0 years. The
      statistical analysis was performed using SPSS software for Windows (version
      12.0). RESULTS: Two hundred and ninety-five students (49.7%) had at least one
      dermatologic lesion. In multivariate analysis, the following factors were
      significantly correlated with dermatological problems: male gender, age > or = 20
      years, history of musical activity > or = 5 years, practice > or = 10 hours/week
      and percussion instruments. Nine types of lesions were determined: corns and
      calluses, pigmentation abnormalities, irritant contact dermatitis, mechanical
      acne, erythema, friction bulla, nail diseases, cicatricial alopecia and allergic
      contact dermatitis. Corns and calluses were significantly the most frequent
      (P<0.001). DISCUSSION: The frequency of dermatological lesions was high compared
      to data reported in the literature, 20 and 32% respectively in the studies by
      Onder and Rimmer. This difference could be due to the greater number of
      percussionists in our study.

PMID- 17507843
TI  - [Clinical and psychological correlation in acne: use of the ECLA and CADI
      scales].
AB  - BACKGROUND: The psychological consequences of acne are frequently unrelated to
      the severity of the actual lesions. Thus, a number of scales have been designed
      and validated to allow quantitation of the severity of acne, such as the ECLA
      scale (Echelle de Cotation des Lesions d'Acne or Acne Lesion Score Scale) while
      others are designed to evaluate quality of life, such as the CADI (Cardiff Acne
      Disability Index) questionnaire recently validated in the French language. The
      purpose of this study was to use both of these scales in individual applications
      in order to determine whether or not any correlation exists between the two
      specific tools and to determine the two groups of patients affected by acne.
      METHODS: One hundred and twenty-eight acne patients (21+/-6.8 years) seen by
      seven dermatologists were included in this study. The severity of their acne was
      evaluated using the ECLA scale; the seven participating dermatologists were
      trained in the use of this scoring system. In addition, patients completed the
      CADI quality-of-life questionnaire after their consultation. Each factor on the
      ECLA was compared with each item in the CADI questionnaire by means of analysis
      of variance. RESULTS: There was no correlation between overall scores on the ECLA
      and CADI scales (r(2)=0.0242). However, a positive correlation was observed
      between overall CADI score and factors F1 and F3 in the ECLA scale (p=0.0085 and
      p=0.0373 respectively). In contrast, the global score on the ECLA scale was
      significantly correlated with item 5 of the CADI questionnaire, namely patients'
      perception of their acne (p=0.0035). CONCLUSION: Acne, even in mild forms, has a
      detrimental psychological effect on patients. The ECLA score coupled with the
      CADI assessment system appear to be two useful and complementary scores for use
      in complete acne patient management.

PMID- 17507844
TI  - [Disseminated molluscum contagiosum during topical treatment of atopic dermatitis
      with tacrolimus: efficacy of cidofovir].
AB  - BACKGROUND: Tacrolimus applied locally is a non-steroid anti-inflammatory drug
      with proven efficacy in atopic dermatitis. Skin infections can occur, especially
      viral infections. CASE-REPORT: A 35-year-old male patient had been treated for
      extensive atopic dermatitis for several months with tacrolimus (Protopic). After
      six months of treatment, he presented a large eruption of molluscum contagiosum,
      in particular on the zones that had received a substantial amount of tacrolimus.
      The treatment was discontinued and application of a preparation containing
      cidofovir led to the patient's quick complete recovery, without recurrence in the
      ensuing months. DISCUSSION: Viral skin infections, in particular poxvirus
      infections, are prompted by topical immunosuppressant treatments such as
      tacrolimus, usually in dose-dependent fashion. Paradoxically, they provide
      protection against bacterial infections by restoring the integrity of the
      cutaneous barrier. Application of cidofovir successfully treated a severe form of
      molluscum contagiosum rapidly without any noticeable adverse effects. This
      confirms several observations about the efficacy and the good safety of this drug
      in the treatment of infections by DNA viruses. It provides an additional
      therapeutic prospect for immunodepressed patients who often present extensive and
      resistant forms of infections that are usually common.

PMID- 17507845
TI  - [Stevens-Johnson syndrome due to lymecycline].
AB  - BACKGROUND: Reports of severe drug-induced bullous reactions to tetracyclines are
      rare. A case of Stevens-Johnson syndrome in a patient treated with lymecycline is
      reported herein. CASE REPORT: A 22 year-old woman with acne was referred for
      Stevens-Johnson syndrome occurring ten days after starting lymecycline. The
      patient was initially treated with high doses of corticosteroid. She presented
      with severe oral and vulvar erosions and erosive cutaneous lesions involving 5 to
      7% of the body surface area. Erosive cutaneous lesions progressively extended to
      20-30% of the body surface area for a 27-day period. Histological analysis of a
      skin biopsy showed epidermal necrolysis typical of toxic epidermal necrolysis.
      Epithelialization of mucosal and cutaneous lesions was achieved 34 days after
      lymecycline withdrawal. CONCLUSION: Stevens-Johnson syndrome is an extremely rare
      reaction to lymecycline. The prolonged development of skin lesions seen here
      after lymecycline withdrawal despite the short half life of the drug is
      surprising. It could have been due to use of strong systemic corticosteroids, as
      described in certain other case reports.

PMID- 17507846
TI  - [Tumoral calcinosis].
AB  - BACKGROUND: Tumoral calcinosis is a rare disease seen in adolescents and young
      adults and consisting of calcifications in periarticular soft tissue. Mutations
      in fibroblast growth factor 23 and GalNAc transferase 3 have been identified in
      the familiar forms of tumoral calcinosis. PATIENT: A 10 year-old boy of light
      phototype presented multiple calcified periarticular masses since the age of
      seven years as well as sciatica secondary to nerve compression. Laboratory
      examinations revealed hyperphosphoraemia. Serum calcium levels, kidney tests,
      parathormone assay and muscle enzymes were all normal. Histology of a cutaneous
      biopsy sample revealed dermal calcifications. Inclan's tumoral calcinosis was
      diagnosed. Surgical resection was performed and drug treatment comprising
      phosphate chelators (aluminium hydroxide) was administered. At five months, other
      sites were apparent. DISCUSSION: This case of tumoral calcinosis is notable in
      terms of its sporadic onset in a child of light phototype and by the presence of
      compression of the external sciatic nerve. The diagnosis was made after ruling
      out other causes of soft tissue calcification.

PMID- 17507847
TI  - [Palmar fasciitis associated with polyarthralgia: rare paraneoplastic syndrome].
AB  - BACKGROUND: Palmar fasciitis associated with polyarthralgia is a rare
      paraneoplastic syndrome, frequently observed in women, and in most cases
      associated with ovarian carcinoma. CASE REPORT: A 51 year-old man complained of
      extensive palmar dermatological lesions associated with polyarthralgia of the
      legs. A few months earlier, cholangiocarcinoma had been diagnosed due to
      cholestatic icterus. The cutaneous biopsy confirmed the diagnosis of palmar
      fasciitis associated with polyarthralgia. DISCUSSION: This paraneoplastic
      syndrome is rarely described in digestive carcinoma and never in
      cholangiocarcinoma. The diagnosis is clinical, confirmed by certain laboratory
      exams. The evolution is similar to that of the carcinoma. Only curative treatment
      can achieve regression of the symptoms.

PMID- 17507848
TI  - [Transformed juvenile-onset mycosis fungoides: treatment by bone marrow
      transplantation with graft-versus-lymphoma effect].
AB  - BACKGROUND: Mycosis fungoides is the most frequent cutaneous T-cell lymphoma but
      has been rarely reported in children and teenagers. Although transformation into
      large-cell T-cell lymphoma has been described in 10% of adult cases, it is seen
      very rarely in children. We report here the clinical case of mycosis fungoides in
      a child with an unusual transformed form at presentation and treated by bone
      marrow allograft. CASE-REPORT: A 13 year-old boy, presenting guttate
      parapsoriasis for 5 years was referred to our Dermatology Department with a 2
      month history of infiltrated plaques throughout the body and face. Large
      erythematous-squamous plaques on the trunk and face as well as a nodular lesion
      of the arm were also noted. On histology, typical features of mycosis fungoides
      were observed, in addition to transformed cells which were CD30-negative. Local
      treatment comprising caryolysin and dermal corticosteroids allowed initial
      regression of the lesions. However, a few months later, nodular lesions
      reappeared as well as axillary lymph nodes. Repeated histology confirmed the
      diagnosis of transformed mycosis fungoides with large CD30-positive cells.
      Despite chemotherapy, cutaneous and lymph node disease recurred, and bone marrow
      allograft was performed, resulting in rapid disease regression. Following the
      recurrence of skin lesions 2 years later, donor lymphocytes were administered in
      addition to treatment with interferon alpha, aiming at stimulating a graft-versus
      lymphoma reaction. One year post-lymphocyte injection, the patient is in full
      remission. DISCUSSION: This is a new case report of juvenile mycosis fungoides
      with unusual clinical features such as rapid course and transformed form at
      presentation. Juvenile mycosis fungoides represents 2.5 to 5% of cases of mycosis
      fungoides and transformation to large cell lymphoma is exceptional. Our case
      illustrates the aggressive pattern observed in some teenage patients as well as
      the efficacy of bone marrow allograft, most likely thanks chiefly to its graft
      versus-lymphoma effect.

PMID- 17507849
TI  - [Purpuric contact dermatitis from Agave Americana].
AB  - BACKGROUND: Irritant papulovesicular dermatitis after cutaneous exposure to the
      sap of Agave Americana, which contains chemical irritants such as calcium oxalate
      and saponins, is well known, but purpuric dermatitis is rare in such cases. CASE
      REPORT: We report the case of a 52 year-old man with purpuric dermatitis of the
      legs mimicking purpura vasculitis that appeared a few hours after he had cut down
      a large Agave with a chain-saw. DISCUSSION: Our case is quite similar to three
      other cases found in the literature. In all four cases the patients had been
      using machines causing projections of plant fragments (chain-saw, trimmer). This
      may have promoted vascular damage, either by direct traumatism or by embedding
      oxalate crystals and saponins in the skin close to small vessels.

PMID- 17507850
TI  - [Hereditary erythermalgia: a model for understanding erythermalgia?].

PMID- 17507851
TI  - [Alopecia areata onset and stressful life events: a pilot study].

PMID- 17507852
TI  - [Isolated pandysautonomia: a rare cause of palmoplantar keratodermia].

PMID- 17507853
TI  - [Black tumor screening and diagnosis in general medical practice: analysis of
      requirements].

PMID- 17507854
TI  - [Surgical management of carboplatin extravasation].

PMID- 17507856
TI  - [A pigmented thigh lesion].

PMID- 17507857
TI  - [Subcutaneous fat necrosis of the newborn].

PMID- 17507859
TI  - [Female genital mutilation].

PMID- 17507860
TI  - [Acute febrile neutrophilic dermatosis (Sweet syndrome)].

PMID- 17507861
TI  - [SAMD9 mutation in normophosphatemic familial tumoral calcinosis].

PMID- 17507862
TI  - [Molluscum contagiosum on a tattoo].

PMID- 17507864
TI  - [Nicorandil and ulceration: new sites].

PMID- 17507865
TI  - [The significance of regulatory CD4+CD25+ T cells in the pathogenesis and
      treatment of kidney disease].
AB  - Thanks to a precisely regulated response, the immune system works to maintain
      homeostasis, and one of the significant mechanisms of this regulation is
      regulatory T cells. This paper presents the latest knowledge concerning the
      occurrence of natural regulatory T cells of CD4+CD25+ phenotype and their role in
      the pathogeneses of immune system diseases. Functional and quantitative disorders
      in this population of cells are found in many diseases which in their course
      attack the kidney, for instance mixed cryoglobulinemia, rheumatoid arthritis,
      Sjogren's syndrome, lupus erythematosus, and type 1 diabetes mellitus. The role
      of T cells and the effectory and regulatory mechanisms dependent on them in the
      development and progression of glomerulonephritis is presented. The role of
      regulatory T cells in the development and progression of chronic kidney disease
      is discussed as well. Qualms whether a decreased number and/or disrupted function
      of regulatory T cells promote the development of autoimmune diseases or whether
      they are secondary phenomena are settled by clinical observations in which
      restoration of the number of the cells prevents further tissue damage.
      Strengthening or blocking regulatory T-cell functions and obtaining a balance
      between activation and suppression in the immune system depending on current
      needs may become the key to the immunotherapy of many diseases. Another problem
      presented in this paper is the perspective of regulatory T cell therapy; however,
      attempts to modify their activity and change the number of cells must be carried
      with the greatest of care because such a procedure may result in dysregulation of
      the immune system.

PMID- 17507866
TI  - [Do antioxidant vitamins influence carcinogenesis?].
AB  - Free radicals can affect the genetic material of cells, causing its gradual
      impairment and mutation. An accumulation of mutations in certain genes might lead
      to neoplasmic transformations of the cells and to cancer development. The
      deteriorative effects of free radicals are counteracted by the antioxidant
      vitamins A, C, and E that quench free radical reactions. Fruits and vegetables
      are excellent sources of antioxidant vitamins. The following article attempts a
      short review of the current knowledge about the influence of vitamins A, C, and E
      on oxidative damage to DNA, the activity of some transcription factors, and the
      expressions of certain genes. The aim of this review is to answer the question
      whether a diet rich in vitamins can protect against cancer.

PMID- 17507867
TI  - [Memory processes and addiction: involvement of the calcineurin signaling
      pathway].
AB  - It has recently emerged that there is a commonality in the molecular mechanisms
      underlying long-term neuronal changes in drug addiction and those mediating
      synaptic plasticity associated with learning and memory. Several lines of
      evidence indicate that the brain regions involved in learning and memory and
      those underlying drug addiction may overlap. Learning and memory processes and
      drug addiction also share intracellular signaling cascades and are associated
      with similar changes in synaptic plasticity. The purpose of the present paper is
      an attempt to further explore the hypothesis that learning and memory are
      essential for the development of addiction. The data suggest that hippocampal
      calcineurin signaling is involved in the long-term adaptation after chronic drug
      treatment in a way that may parallel its role during memory formation. Such an
      effect is consistent with the common molecular mechanisms shared by addiction and
      memory processes. Given the well-established role of the hippocampus in
      associative learning and memory, this paper further emphasize the important role
      of this forebrain structure in controlling long-lasting features of addiction.

PMID- 17507868
TI  - [Proteus bacilli: features and virulence factors].
AB  - In this article, different aspects of virulence factors of Proteus bacilii (P.
      mirabilis, P. vulgaris, P. penneri i P. hauseri) are presented. These are
      opportunistic pathogens that cause different kinds of infections, most frequently
      of the urinary tract. These bacteria have developed several virulence factors,
      such as adherence due to the presence of fimbriae or afimbrial adhesins,
      invasiveness, swarming phenomenon, hemolytic activity, urea hydrolysis,
      proteolysis, and endotoxicity. Below we focus on data concerning the molecular
      basis of the pathogenicity of Proteus bacilli.

PMID- 17507869
TI  - Immune reconstitution diseases: is it possible to establish recommendations?
AB  - The introduction of combination antiretroviral therapy (cART) has attracted the
      attention of scientists and physicians all over the world to the phenomenon known
      as IRD, immune restoration disease. The management of IRD depends on the correct
      diagnosis of the syndrome, which can be difficult to establish. The atypical
      presentation and unpredictable course of the disease may require individual
      decisions regarding a delay of cART or its interruption as well as the use of
      corticosteroids. Thus the frequent need for individualized management of IRD can
      make it difficult to obtain enough results from prospective randomized trials to
      establish strict recommendations. However, they should be initiated as soon as
      possible.

PMID- 17507871
TI  - [Interceptors:--"silent" chemokine receptors].
AB  - The physiological effect caused by chemokines is regulated by interactions with a
      group of rodopsin-like G protein-coupled receptors (GPCRs). These receptors share
      a number of common features: the polypeptide chain is a 7-transmembrane ?-helix
      (7 TMD motif) and the region involved in G-protein interaction (the DRYLAIV
      sequence) is located in the second transmembrane loop. So far, 19 chemokine
      receptors have been identified. Three of them (Duffy glycoprotein, D6, and CCX
      CKR proteins), although structurally related to other GPCRs, lack the ability of
      G-protein signal transduction. Instead, they efficiently internalize their
      cognate ligands, regulating chemokine levels in various body compartments. These
      three proteins are suggested to form a distinct chemokine receptor family,
      designated "interceptors" or "silent" chemokine receptors.

PMID- 17507872
TI  - [The role of fucosylation of glycoconjugates in health and disease].
AB  - Fucose is a deoxyhexose that is present in the L-configuration of many N- and O
      linked oligosaccharide structures of membrane as well as soluble glycoproteins
      and glycolipids produced by mammalian cells. The fucose molecule is present in
      ABH blood group antigens and in some oligosaccharide structures belonging to the
      Lewis(x), Lewis(y), Lewis(a), and Lewis(b) antigens. Characteristic of fucose is
      its almost exclusive presence at a terminal position, i.e. not inserted in an
      oligosaccharide chain. Fucose can be alpha 1,2, alpha 1,3, alpha 1,4, and alpha
      1,6 linked to the glycans of glycoconjugates. This predisposes fucose to play a
      crucial role in biological recognition events, such as cell-cell and cell-matrix
      interactions. In the present review the influence of fucose on the properties and
      biological functions of glycoproteins is described. The state of current
      knowledge on the role of fucosylglycotopes, fucose-containing glycans, in many
      physiological processes, such as fertilization, embryogenesis, fetal development,
      neuron transmission, leukocytes adhesion, signal transduction, and apoptosis, as
      well as in diseases, such as rheumatoid arthritis, cystic fibrosis, peptic ulcer
      disease, inflammatory process, and cancer, is summarized. Finally, some examples
      of changes in fucose expression and its possible determination as a marker for
      diseases diagnosis and monitoring are shown.

PMID- 17507873
TI  - [The influence of isoflavonoids on the antitumor activity of vitamin D3].
AB  - Isoflavonoids exert a regulatory function on the expression of cytochrome P450
      enzymes and also up-regulate the vitamin D(3) receptor (VDR) on cancer cells,
      which increase their sensitivity to 1,25-dihydroxyvitamin D(3) , the hormonally
      active form of vitamin D(3) . Isoflavonoids are also able to raise the serum
      level of the active form of vitamin D(3) due to their inhibitory activity on
      CYP24, the enzyme involved in the degradation of 1,25-dihydroxyvitamin D(3) and
      its precursor 25-OH-D(3) to inactive compounds. Another enzyme, CYP27B1, involved
      in the synthesis of 1,25-dihydroxyvitamin D(3) , is stimulated by isoflavonoids,
      and this may result in a similar effect of increasing in the serum level of 1,25
      dihydroxyvitamin D3. CYP27B1 and CYP24 were found in kidneys (the main location
      of 1,25-(OH) (2)D(3) synthesis) and also in brain cells, osteoclasts,
      keratinocytes, macrophages, intestine epithelial cells, and in some cancer cells.
      The expression of VDR was detected not only in the cells primarily targeted by
      1,25-dihydroxyvitamin D3, but also in epithelial and mesenchymal cells.
      Therefore, combined treatment with isoflavonoids and 1,25-dihydroxyvitamin D3
      might be effective in both cancer prevention and treatment.

PMID- 17507874
TI  - Lactoferrin in health and disease.
AB  - Lactoferrin, an iron-binding glycoprotein, can be regarded as a cell-secreted
      mediator that bridges innate and adaptive immune function by regulating target
      cell response. It is a major pleiotropic mediator that directly assists in the
      development of T-helper cell polarization. The aim of this minireview is to
      provide a summary of the most recent work presented at the Lactoferrin
      Minisymposium at the University of Texas, Health Science Center at Houston,
      Texas, USA, regarding role of lactoferrin in maintaining immune homeostasis. The
      data presented here lay emphasis on the significance of lactoferrin in the
      resolution or progression of the immune responses, thus giving lactoferrin
      bookend properties in controlling the initial reactions to infectious assault,
      trauma, and injury. These findings may be critically important in the development
      of therapeutically relevant protocols.

PMID- 17507875
TI  - Iron-mediated dismutation of superoxide anion augments antigen-induced allergic
      inflammation: effect of lactoferrin.
AB  - INTRODUCTION: The authors previously showed that pollen grain-, pollen grain
      extract-. and subpollen particle-induced allergic inflammation in lungs and eyes
      is robustly augmented by their intrinsic NAD(P)H oxidase activity. Here they
      sought to determine whether lactoferrin (LF), an iron-binding protein and immune
      modulator, decreases allergic inflammation induced by ragweed (Ambrosia
      artemisiifolia) pollen grain extract (RWE). MATERIAL/METHODS: The impact of LF on
      NAD(P)H oxidase in pollen grains and reactive oxygen species (ROS) levels in
      vitro and in the lungs of experimental animals was assessed by use of redox
      sensitive probes and specific inhibitors. The influence of LF on RWE-induced
      allergic inflammation was determined in a mouse experimental model of asthma.
      RESULTS: The data show that the intrinsic NAD(P)H oxidase of pollen grains
      generates superoxide anion (O2-) and that LF does not alter its enzymatic
      activity, as shown by nitroblue tetrazolium and cytochrome c assays. On the other
      hand, LF significantly decreased H(2)- O(2)- and lipid peroxide (4-hydroxynoneal
      and malondialdehyde) levels in airway lining fluids and lung epithelium after
      intranasal challenge of naive or sensitized mice with RWE. Furthermore, a single
      dose of LF prevented/decreased the abundance of the RWE-induced robust
      accumulation of inflammatory and mucin-producing cells in airways and
      subepithelial compartments and decreased airway hyperreactivity. CONCLUSION:
      These data suggest that the reduced conversion of NAD(P)H oxidase-generated O(2)-
      into H(2)- O(2)- and/or OH, which in turn synergistically enhanced pollen antigen
      induced airway inflammation, is due to the iron-binding capacity of LF. These
      results support the utility of LF in human allergic inflammatory disorders.

PMID- 17507876
TI  - Lactoferrin modulation of antigen-presenting-cell response to BCG infection.
AB  - INTRODUCTION: Lactoferrin, an 80-kDa basic N-glycoprotein, has been identified as
      a potent immune modulator. When used experimentally as an adjuvant in mice,
      lactoferrin can boost the efficacy of the BCG vaccine to increase delayed type
      hypersensitive responses and to limit subsequent pathology upon infection with
      virulent mycobacterium. These studies outline preliminary findings to examine the
      multiple mechanisms of action of lactoferrin on antigen-presenting cells which
      would enhance vaccination and bridge the innate and adaptive responses.
      MATERIAL/METHODS: Bone marrow-derived macrophages (BMMs) and human and murine
      cells lines were infected with BCG in the presence or absence of bovine
      lactoferrin. The cells were examined for changes in uptake of BCG post infection
      and increases in the surface expressions of Class I or Class II molecules by flow
      cytometric analysis. Infected cultures were collected to examine cytokine
      production by ELISA. RESULTS: Lactoferrin was found to significantly increase the
      uptake of BCG organisms during infection of BMMs and human monocyte cell lines.
      Lactoferrin added to BCG-infected BMMs demonstrated significantly increased
      surface expression of Class II (I-Ab), but no change in Class I (H-2kb)
      molecules. In addition, BCG-infected cells incubated in the presence of
      lactoferrin demonstrated a significant increase in relative IL-12 to IL-10 ratios
      in a dose-dependent manner. CONCLUSIONS: Overall, lactoferrin was able to alter
      BCG-infected antigen-presenting cells (APCs) in vitroin a manner consistent with
      the induction of responses required for successful presentation of antigen to the
      adaptive arm of the immune response, which would lead to the generation of strong
      T-helper 1 type immunity.

PMID- 17507877
TI  - Immunoregulatory function of lactoferrin in immunosuppressed and autoimmune
      animals.
AB  - In this article we review our recent results on the effects of lactoferrin (LF),
      given orally, on the immune status of mice subjected either to chemotherapy or
      immobilization stress as well as on rats with experimentally induced autoimmune
      encephalomyelitis (EAE). We demonstrated that LF accelerated reconstitution of
      the immune system function after administration of a sublethal dose
      cyclophosphamide (CP) and normalized the ratio of major blood cell types in that
      model. Also, after application of methotrexate (MTX) LF was effective to speed up
      reconstitution of the cellular and humoral immune response. Mice treated with
      lethal dose of busulfan (Bu) and CP and reconstituted with bone marrow cells
      (BMC) were able to quicker develop optimal immune responses when administered LF.
      In addition LF was shown to accelerate engraftment of bone marrow cells from
      syngeneic donors in that model. Using immobilization stress model was shown that
      LF accelerates reconstitution of the cellular and humoral immune response. In
      rats with EAE lactoferrin lowered the clinical score of the disease and
      diminished pathohistological changes in the spinal cord. In summary, in a series
      of studies we demonstrated a benefit of orally administered LF in
      immunocompromised animals.

PMID- 17507878
TI  - Multiscale extraction of hypodensity in hyperacute stroke.
AB  - BACKGROUND: Stroke is a syndrome characterized by a sudden neurological deficit
      caused by cerebral ischemia. Computed tomography (CT) plays a crucial role in the
      evaluation of stroke patients even though it is not sufficient enough to extract
      the hypodense area corresponding to the infracted cerebral tissues in hyperacute
      stage. Careful selection of patients for thrombolytic therapy is fundamental to
      improve safety and efficacy; therefore the authors propose an additional, wavelet
      based post-processing method for extracting hypodensity in CT scans in hyperacute
      stroke patients. MATERIAL/METHODS: A retrospective evaluation of 52 sets of
      examinations conducted in patients admitted with symptoms suggestive of stroke
      was undertaken by four radiologists unaware of the final clinical findings. All
      of the selected cases were considered as having no direct signs of hyperacute
      ischemia in the localization corresponding with clinical manifestation and follow
      up studies. In the first stage, only CTs performed at admission were evaluated; a
      month later the same scans were reevaluated with additional use of a "stroke
      monitor". All sets were evaluated independently. Follow-up CT exam and/or the
      clinical picture confirmed or excluded the diagnosis. RESULTS: Higher AUC values
      were found for the "stroke monitor"-aided radiological diagnosis for all the
      radiologists and the differences were significant for all subgroups (p<0.05)
      apart from the subgroup in which CT scans of patients with significant cerebral
      atrophy were excluded. CONCLUSIONS: Combining the results of CT and the "stroke
      monitor" provided a better diagnosis of stroke, especially in atrophic brains.
      Planned prospective studies will allow evaluation of the impact on the further
      treatment of hyperacute stroke patients.

PMID- 17507879
TI  - Relationship between frontal N-acetylaspartate and cognitive deficits in first
      episode schizophrenia.
AB  - BACKGROUND: The aim of this study was to evaluate the relationship between N
      acetylaspartate (NAA) levels in selected brain regions and cognitive performance
      in patients with first-episode schizophrenia. MATERIAL/METHODS: Thirty patients
      (20 male, 10 female; mean age: 22.5 years) with the diagnosis of first-episode
      schizophrenia and 19 comparable healthy controls were studied. The Wisconsin Card
      Sorting Test (WCST) was used to assess cognitive functions. MR imaging and MR
      spectroscopy examinations were performed on a 1.5 T scanner. Voxels of 8 cm3 were
      positioned in the left frontal lobe, left temporal lobe, and left thalamus. The
      ratio of NAA to creatine and the ratio of NAA to unsuppressed water signal were
      analyzed. RESULTS: Patients performed significantly worse than controls on
      measures of the WCST. In the patient group, NAA levels in the frontal lobe were
      significantly related to poorer WCST performance. CONCLUSIONS: Cognitive
      impairment related to dysfunction of the prefrontal cortex in first-episode
      schizophrenia is associated with NAA level in the frontal lobe.

PMID- 17507880
TI  - N-acetylaspartate (NAA) levels in selected areas of the brain in patients with
      chronic schizophrenia treated with typical and atypical neuroleptics: a proton
      magnetic resonance spectroscopy (1H MRS) study.
AB  - BACKGROUND: NAA, marker of neurons integrity and viability, is one of the most
      important brain metabolites visible in 1H MRS. In most studies of schizophrenia,
      the decrease of NAA level was observed in the temporal, frontal lobes and in the
      thalamus. This finding was observed more often among chronic patients, what
      suggests the influence of disease duration or the effect of neuroleptic
      treatment. The aim of the present study was the comparison of NAA levels in brain
      of schizophrenic patients taking typical and atypical neuroleptics.
      MATERIAL/METHODS: We analyzed the NAA levels in selected brain areas in 58
      schizophrenic patients and 21 healthy controls. 10 patients were treated with
      typical neuroleptics, 10 patients with clozapine, 17 received olanzapine and 21 -
      risperidone. 1H MRS was performed on a 1,5 MR scanner with PRESS sequence. Voxels
      of 2x2x2 cm were localized in the left frontal, left temporal lobe and left
      thalamus. RESULTS: There were no differences in NAA levels between patients on
      typical and atypical medications analyzed together and separately (olanzapine,
      clozapine and risperidone groups). We also did not find any differences between
      patients taking selected atypical neuroleptics and controls. The NAA level in the
      thalamus in the group of patients receiving typical antipsychotics was the lowest
      among all groups and differed significantly from healthy controls. CONCLUSIONS:
      The results of our study suggest that atypical neuroleptics may have favorable
      effect on NAA concentration in brain of schizophrenic patients. Decrease in NAA
      level in patients taking typical medication may be caused by the progression of
      the disease or by the direct action of these drugs.

PMID- 17507881
TI  - Analysis of correlation between the degree of cognitive impairment and the
      results of perfusion CT in patients with dementia.
AB  - BACKGROUND: The aim of the study was to assess the relationship between cognitive
      impairment according to the Mini Mental State Examination (MMSE) and values of
      cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time
      (MTT) obtained in perfusion CT (pCT). MATERIAL/METHODS: Sixty-four patients with
      dementia (36 with Alzheimer's disease, 15 with vascular dementia, and 13 with
      mixed dementia), aged 45-92 years (mean: 69.9 years) with different degrees of
      cognitive impairment (mean MMSE score: 17.0) were involved in the study. All
      subjects underwent pCT at the level of the basal ganglia (50 scans, 1 scan/s, 40
      ml contrast medium at 4 ml/s, delay: 7 s). CBF, CBV, and MTT values from 31
      regions of interest (ROIs) in the gray and white matter of the frontal and
      temporal lobes, lentiform nuclei, and internal capsules were correlated with the
      MMSE scores. RESULTS: Statistical analysis of CBF and MMSE revealed significant
      correlations in 22/31 ROIs including the gray and white matter of the frontal and
      temporal lobes, both internal capsules, right and left hemispheres, and total
      gray and white matter. Analysis of CBV and MMSE showed significant correlations
      in 21/31 ROIs in the gray and white matter of the frontal and temporal lobes,
      both internal capsules, left lentiform nucleus, right and left hemispheres, as
      well as total gray matter. There were no significant correlations between MTT and
      MMSE. CONCLUSIONS: CBF and CBV calculated with pCT correlate with cognitive
      impairment in patients with dementia and thus may play a role in monitoring
      disease progression or therapeutic response.

PMID- 17507882
TI  - Prediction of deterioration of mild cognitive impairment with CT and SPECT.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is a condition referring to persons
      with significant memory impairment, often accompanied by functional deficits in
      the attention, language, visuospatial, and psychomotor domains, who do not
      fulfill the criteria for dementia. Individuals with MCI are at an increased risk
      of developing dementia. The objective of this study was to examine baseline
      differences between MCI subjects who did or did not deteriorate at follow-up on
      measures of cognition and neuroimaging. MATERIAL/METHODS: MCI individuals (n=105)
      enrolled in a longitudinal study at the Alzheimer's Day Clinic in Warsaw received
      annual clinical and psychometric examinations for up to a mean of three years. At
      baseline, all patients received temporal lobe-oriented CT and 99mTc HMPAO SPECT.
      The diagnosis of MCI according to Mayo Clinic Petersen's Criteria was conducted
      by a panel of specialists and neuropsychological testing was completed on all
      subjects. RESULTS: After three years of follow-up, 42 subjects remained stable or
      had improved (8) and 63 had progressive cognitive disturbances, including 23 who
      converted to dementia. Compared with stable MCI patients, decliners have
      significantly higher radial width of the temporal horn bilaterally and width of
      the lateral part of the transverse fissure on the right, dilated third ventricle,
      and smaller oblique thickness of the anterior part of the hippocampal formation
      bilaterally at the baseline. No significant differences in SPECT perfusion were
      found between the two groups. CONCLUSIONS: The proposed linear measurements of
      atrophy in CT may constitute a predictor for those MCI patients who are more
      likely to deteriorate.

PMID- 17507883
TI  - Trigeminal nerve - artery contact in people without trigeminal neuralgia - MR
      study.
AB  - BACKGROUND: Neurovascular conflict is regarded as the most common cause of
      idiopathic trigeminal neuralgia. It is suspected that a blood vessel in contact
      with the root entry zone of a trigeminal nerve causes its irritation. The aim of
      the study was to evaluate how signs of neurovascular conflict can be found in
      people without trigeminal neuralgia MATERIAL/METHODS: The study was conducted
      retrospectively. The authors analyzed MR examinations of 60 patients (120
      nerves), aged 22-77 years, who did not have trigeminal neuralgia or related
      symptoms. Nerve-artery contact at the root entry zone of a trigeminal nerve,
      nerve deformation, and atrophy were searched for in angio-3D-TOF images (slice
      thickness: 1 mm). RESULTS: Contact between a trigeminal nerve and an artery was
      found in 30 cases (25% of nerves). The blood vessel was parallel to the nerve
      root in 14 cases (11.7%) and crossed it at a right or acute angle in 15 cases
      (12.5%). Contact between artery and atrophic nerve was found in one case.
      Modeling of the trigeminal nerve by an artery was not found. CONCLUSIONS: Contact
      between a trigeminal nerve root and an artery in the prepontine cistern is a
      frequently seen anatomical variant. Therefore, detection of such a variant is not
      equivalent to finding the cause of a patient's complaints.

PMID- 17507884
TI  - Magnetic Resonance evaluation of disease activity in Graves' ophthalmopathy: T2
      time and signal intensity of extraocular muscles.
AB  - BACKGROUND: It is accepted that T2-weighted imaging can demonstrate the extent of
      an inflammatory process in Graves' ophthalmopathy (GO). This aim of this study
      was a comparative evaluation of the most commonly used indicators of extraocular
      muscle pathophysiology, i.e. signal intensity (SI) and T2-time (T2-t) in
      correlation with muscle volume (MV), and to determine the need to make the above
      indicators objective with regards to clinical practice. MATERIAL/METHODS: MRI
      examinations in a 1.5 T scanner of 40 orbits formed the study group. Quantitative
      assessment of the muscles was carried out using a numerical segmentation imaging
      technique (NSI). SI and T2-t were measured for each muscle. A standardization
      algorithm was applied based on T2-t and IS from the ipsilateral white matter of
      the frontal lobes. RESULTS: The correlation between T2-t and MV for the medial
      rectus and inferior rectus muscles (IRM) was at a comparatively high level (R:
      0.49 and 0.47), with a value as high as R=0.58 for the superior rectus muscle.
      Correlation between SI and volume for these muscles was found to be at R-levels
      of 0.37, 0.48, and 0.46. Correction of the T2-t and SI values with use of a
      standardization algorithm in most cases did not change the above correlations,
      except for IRM. CONCLUSIONS: The parameter with the higher correlation to the
      symptoms of GO is T2 The value of SI as an indicator of disease intensity in GO
      that can be used without the use of multiple echo sequences was confirmed. It is
      necessary to make the above parameters objective relative to white matter when
      calculating IS for the inferior rectus muscle.

PMID- 17507885
TI  - Utility of computed tomography and selected MR sequences in the diagnostics of
      patients with partial epileptic attacks.
AB  - BACKGROUND: Epilepsy is a disease which manifests itself with recurrent
      dysfunction of the brain. Epilepsy thus becomes a serious social problem and it
      is therefore necessary to introduce more and more up-to-date methods of its
      diagnostics. MATERIAL/METHODS: Examinations were performed on 85 patients with
      partial epileptic attacks. The study group included 43 women and 42 men who had
      suffered from epilepsy for 2 to 40 years. CT and MR examinations were performed
      in the interparoxysmal period. In MRI, T1-weighted images before and after
      contrast administration, T2- and PD-weighted images, and FLAIR images were
      analyzed. RESULTS: Agreement between the location of lesions in CT and EEG was
      evaluated with the kappa test and amounted to 0.29. Low compatibility was also
      found between MR and EEG and amounted to 0.33. However, compatibility between the
      location in CT and MR reached the level of 0.62. The most common abnormalities
      were asymmetry of the lateral ventricles (most often temporal horns), cortical
      scars, mesial temporal sclerosis (MTS), and CNS tumors. T1- and T2-weighted
      images enabled recognition of most of the focuses, but they failed to visualize
      some of the degenerative lesions in the hippocampus which were recognizable in
      coronal FLAIR. No statistically significant correlation was found between the
      patient age, duration of the disease, and type of lesion and its location.
      CONCLUSIONS: The performed examinations showed that MR is the method of choice in
      patients with temporal epilepsy. The study protocol should include the FLAIR
      sequence in the coronal plane, which has high sensitivity in recognizing lesions
      within the hippocampus.

PMID- 17507886
TI  - Diagnostic cerebral angiography affects the tonus of the major cerebral arteries.
AB  - BACKGROUND: Vascular reactions after cerebral angiography have not been hitherto
      extensively explored due to the lack of a simple, easily available, and safe
      method for the measurement of cerebral circulation. We attempted to study
      cerebral circulation with color Doppler transcranial sonography (TCCS) in
      consecutive patients before and immediately after digital subtraction angiography
      (DSA). MATERIAL/METHODS: TCCS examination of the major cerebral arteries was
      carried out in 52 patients (25 females and 27 males), mean age 50.3+/-11.5 years,
      before and 10-20 minutes after cerebral angiography. A Toshiba Aplio SSA 770A
      system with a 2.5-MHz sector transducer was used. RESULTS: In general terms,
      there was a tendency after DSA towards a slight decrease in peak systolic blood
      velocity and an increase in mean and end-diastolic velocity in all the major
      cerebral arteries which, in turn, led to a decrease in the impedance index
      (pulsatility index, PI). In 19 patients, the impedance index as measured in the
      middle cerebral artery decreased after DSA, in 29 it did not change, while in 4
      patients PI increased. Discriminant analysis showed that the factors predisposing
      individuals to these adverse reactions were a low score on the Glasgow Coma
      Scale, etiological diagnosis of intracerebral bleeding, and a high value of the
      impedance index prior to the procedure. CONCLUSIONS: Contrast cerebral
      angiography may affect the tonus of cerebral vessels. In the majority of patients
      it caused vasodilatation to varying degrees and in a small sub-group
      vasoconstriction.

PMID- 17507887
TI  - MR-angiography as a method for evaluating endovascular coiled cerebral aneurysms.
AB  - BACKGROUND: The aim was to compare digital subtraction angiography (DSA) with
      magnetic resonance angiography (MRA) in evaluating intracranial aneurysms
      embolized with Guglielmi Detachable Coils (GDCs) and to assess 3D TOF MRA source
      data, maximum intensity projection (MIP), and 3D iso-surface reconstruction in
      the follow-up of patients with cerebral aneurysms treated with GDC.
      MATERIAL/METHODS: 3D TOF MRA source data, MIPs, and 3D iso-surface
      reconstructions of 32 GDC coiled aneurysms were compared with DSA images in the
      follow-up of 28 patients. Images were assessed for parent and branch artery flow,
      the presence of neck recurrence, and aneurysm regrowth. RESULTS: In the DSA
      follow-ups of the 32 aneurysms there was no flow in the embolized aneurysm in 20
      (62.5%), flow between the coil loops was found in 11 (34%), and the neck flow was
      observed in 8 (25%). There was good correlation for all these features when the
      3D iso-surface MRA and source data were compared with DSA. The correlation
      between MIP MRA and DSA was less robust. The correlation was very good in 21 of
      the 32 aneurysms (65.62%), good in 6 (18.75%), acceptable in 3 (9.37%), and weak
      and non-diagnostic in 2 (6.25%). Additional information can be obtained by
      performing plain film x-rays of the skull to demonstrate a change in the coil
      ball configuration. MRA did not detect any residual aneurysm neck in 2 cases.
      CONCLUSIONS: MRA is a promising technique to evaluate GDC coiled cerebral
      aneurysms; however, it cannot substitute DSA.

PMID- 17507888
TI  - Measurements of the middle cerebral artery in digital subtraction angiography and
      MR angiography.
AB  - BACKGROUND: The middle cerebral artery (MCA) has an individually varied
      anatomical type and course. Age and sex variability of MCA have not been
      completely defined. The aim was to define the range of normal values of widths
      and lengths of particular MCA segments, define age and sex variability, and
      compare the compatibility of MCA measurements of digital subtraction angiography
      (DSA) and MR angiography (MRA). MATERIAL/METHODS: The study was a retrospective
      evaluation of 114 examinations of cerebral vessels (88 DSA, 26 MRA). It included
      patients in whom the angiographic examinations did not show any pathological
      lesions. DSA was carried out using a routine protocol applied to examinations of
      cerebral arteries; MRA was performed with a 1.5 T scanner and the time of flight
      (TOF) method using the fast gradient echo sequence with RF spoiler- multivolume
      RF-FAST. The diameter measurements of the internal carotid arteries (ICA) and
      segments of the MCA were based on DSA and MRA; the study also included the
      lengths of MCA segments from the origin to the first first ramification and from
      the origin to the bifurcation. RESULTS: The width and length ranges of particular
      MCA segments in a group of healthy patients were defined by DSA and MRA. The
      diameters of ICA and MCA and its upper branch are age and sex dependent, being
      wider in men than in women and increasing with age. CONCLUSIONS: MR angiography
      is a fully reliable method allowing assessment of middle artery morphology, but
      precise evaluation of the widths of the artery and arterial branches with MRA
      should include the source images of the vascular sequence.

PMID- 17507889
TI  - Doppler ultrasound criteria of physiological flow in asymmetrical vertebral
      arteries.
AB  - BACKGROUND: Numerous publications have documented the usefulness of carotid
      ultrasonography. However, few studies report on criteria of flow evaluation in
      vertebral arteries. One reason is the greater anatomical variety of vertebral
      arteries, particularly the often encountered diameter asymmetry between sides.
      The purpose of this study was to assess the dependence of hemodynamics in
      vertebral arteries on their side-to-side diameter asymmetry. MATERIAL/METHODS:
      Prospective color Doppler ultrasonography examinations of the vertebral arteries
      were performed on 113 adult volunteers (69 females, 44 males, mean age: 29.1+/
      6.9 SD), free of symptoms of vertebrobasilar insufficiency, atherosclerotic
      lesions, anatomic anomalies, or signs of significant stenosis in spectral
      Doppler. The subjects were divided into four groups according to the degree of
      asymmetry between sides. RESULTS: There were no statistically significant
      differences in the hemodynamics of the arteries with side-to-side diameter
      asymmetry of less than 25% (or 0.5 mm). In the remaining three groups, flow
      parameters differed considerably between sides. End diastolic velocity revealed
      the greatest dependence on diameter asymmetry. CONCLUSIONS: Assessment of the
      hemodynamics of vertebral arteries should take side-to-side asymmetry into
      consideration. Arteries differing in diameter by up to 25% or 0.5 mm can be
      considered symmetrical. The most vulnerable flow parameter to side-to-side
      diameter asymmetry is the end diastolic velocity.

PMID- 17507890
TI  - Ultrasonographic and histological analysis of atheromatous plaques in carotid
      arteries and apoplectic complications.
AB  - BACKGROUND: The aim of the study was to compare a computer assessment of carotid
      plaques with the quantity and distribution of inflammatory cells in the plaques
      and to find correlation with the incidence of cerebral stroke. MATERIAL/METHODS:
      The material consisted of 20 carotid plaques causing stenoses of internal carotid
      arteries ranging from 70 to 99%. USG images of the plaques were assessed by a
      computer-assisted program for image analysis. For each plaque a histogram was
      obtained for which the gray scale median (GSM), a measure of plaque echogenicity,
      was determined. Then the quantity and distribution of inflammatory cells in
      plaques taken during endarterectomy were assessed and these data were compared
      with the GSM and the incidence of stroke. Moreover, grouping of cases according
      to histometric variables was analyzed. RESULTS: Statistical analysis showed a
      considerable correlation between low GSM and the incidence of stroke. At the same
      time, a correlation between the presence of inflammatory cells on the edges of
      plaque with a low GSM was found and the analysis of clusters demonstrated a
      significant increase in the number of patients with strokes. CONCLUSIONS: The use
      of computer analysis of USG images allows determining the echogenicity of any
      carotid plaque and can be applied in clinical studies in which the aim is to find
      characteristic parameters for an unstable plaque.

PMID- 17507891
TI  - Coronary artery calcifications in renal graft recipients at the time of
      transplantation.
AB  - BACKGROUND: Coronary artery calcifications (CACs) represent an important risk
      factor of coronary artery disease in the general population. The purpose of the
      study was to determine the amount of CAC, including calcium mass, in renal graft
      recipients early after transplantation. MATERIAL/METHODS: Forty-nine patients
      aged 43.7+/-9.8 years underwent CAC determination with multi-detector row
      computed tomography within two weeks after transplantation. The calcium scores
      were compared with the clinical and laboratory data of the subjects. RESULTS:
      CACs were detected in 73% of the subjects. The mean calcium score (CS) was
      500.8+/-1100.4 and the mean calcium mass (CM) 127.0+/-228.6 mg. Presence of
      diabetes, duration of hypertension, and diastolic blood pressure (DBP) were
      significantly associated with the presence of CAC in univariate analysis. CS and
      CM positively correlated with duration of hypertension, time on dialysis, and
      pulse pressure (PP) and negatively with DBP. In multiple regression analysis the
      duration of hypertension, DBP, and PP were identified as independent predictors
      of CAC presence (p<0.01), while the time on dialysis and DBP were independent
      predictors of CAC severity (p<0.02). CONCLUSIONS: The results suggest that
      hypertension may play a crucial role in the development of coronary artery
      calcifications in end-stage renal disease patients, but the nature of the
      relation between CAC and blood pressure needs further investigation.

PMID- 17507892
TI  - The role of magnetic resonance imaging (MRI) with magnetic resonance
      cholangiopancreatography (MRCP) in the diagnosis and assessment of resectability
      of pancreatic tumors.
AB  - BACKGROUND: Carcinoma of the pancreas is one of the most malignant tumors.
      Symptoms are usually nonspecific and insidious, such that the cancer is advanced
      by the time of diagnosis. The aim of the study was to assess the usefulness of
      MRI and MRCP in the diagnosis of patients suspected of pancreatic carcinoma and
      to define the role of these methods in the evaluation of resectability of
      pancreatic cancer in comparison with surgical findings. MATERIAL/METHODS: Forty
      seven patients (32 men and 15 women) aged 46-81 had undergone MRI and MRCP
      examination of the upper abdomen on a 1.5 T system with a standard flexible
      surface coil. The results of those tests were compared with surgical and
      histopathological findings. The capacity of MR and MRCP to detect pathological
      mass, assess the nature of the disease process, and accurately assess the
      resectability of the malignant lesion were evaluated. In the statistical analysis
      the chi-squared and Fisher's precise tests were performed. RESULTS: Statistical
      analysis showed 87% sensitivity, 97% specificity, and 95% accuracy of MRI and
      MRCP in the evaluation of the nature of tumors within the pancreas and 100%
      sensitivity, 90% specificity, and 93% accuracy in determining the resectability
      of the lesion. The positive predictive value came to 83%, while the negative
      predictive value was 100%. The kappa compatibility index in comparison with
      surgical findings was 0.85714. CONCLUSIONS: MR and MRCP is an important
      diagnostic method in assessing pancreatic tumors. It is very useful in
      differential diagnosis and determination of tumor resectability.

PMID- 17507893
TI  - Palliative percutaneous kidney embolization with enbucrilate in patients with
      renal cell carcinoma: safety and symptom control.
AB  - BACKGROUND: Primarily palliative renal embolization is a relatively rare
      procedure which is indicated in patients with unresectable kidney malignancies
      and in patients in poor general condition. The aim of this paper was to evaluate
      the role of primarily palliative transarterial renal embolization for the
      treatment of inoperable patients with renal cell carcinoma, assessing the
      indications, safety, and efficacy of this procedure. MATERIAL/METHODS: Seventy
      three patients scheduled for palliative embolization between 1998 and 2005 were
      retrospectively analyzed regarding their medical history, the procedure report,
      and data from the early postoperative period. RESULTS: Sixty-six of the 73
      patients presented with renal cell carcinoma stage IV. The most common indication
      for embolization was hematuria (34%), followed by flank pain (32%), prophylaxis
      in stage IV (25%), lack of consent for surgery (7%), and poor general condition
      (3%). Embolizations were performed under local anesthesia with a mixture of
      enbucrilate and iodinated oil, with the use of additional embolizing materials in
      two cases. The procedure eliminated hematuria in 100% of cases and removed the
      loin pain completely in 72%. Migration of the embolizing material was observed in
      10% of cases, and in 4% it resulted in symptomatic occlusion of the lower
      extremity distal arteries. Postembolic syndrome was noted in 92% of the patients
      CONCLUSIONS: Percutaneous palliative embolization with enbucrilate is a safe and
      effective method of treating patients with unresectable renal cell carcinoma. The
      potential effect of the embolization on cancer progression and improvement of
      survival in these patients still requires prospective investigation.

PMID- 17507894
TI  - Diagnostic performance of CT colonography in a population with high prevalence of
      large bowel disease.
AB  - BACKGROUND: Although CT colonography (CTC) is a well-known diagnostic modality,
      it is not yet established as an official screening method mainly due to
      discrepancies in diagnostic accuracy values reported in the literature. We
      examined the diagnostic accuracy of CTC in a population with suspicion of large
      bowel disease. MATERIAL/METHODS: CTC was performed in 77 patients with 2- and 16
      slice CT units after the standard preparation. The results were compared with
      optical colonoscopy (39%) and/or barium enema (35%) and pathomorphological
      examinations (44%) and statistically evaluated. RESULTS: CTC visualized large
      bowel pathology in 75% of patients. Its diagnostic accuracy vs. optical
      colonoscopy was significant (C=0.8719, p<0.0001) and higher than that of barium
      enema (C=0.7774, p<0.0001). CTC was the most accurate in the diagnosis of
      colorectal carcinoma (C=0.7071). There was statistically significant accuracy
      between CTC and optical colonoscopy in the evaluation of polyps diameter
      (C=0.7657), localization (C=0.8913), and morphology (C=0.7568). CTC was the most
      accurate in depicting large polyps (<10 mm): its sensitivity was 100% and
      specificity 98%. The diagnostic accuracy of CTC was also statistically
      significant compared with pathomorphology (C=0.7812, p<0.0001). In 78% of the
      examined patients, extra-colonic findings were visualized with CTC, 13% of which
      were clinically important and 22% of which had been occult before. CONCLUSIONS:
      The diagnostic accuracy of CTC in patients from a population with a high
      prevalence of large bowel disease was statistically significant. It also enabled
      the visualization of pathological findings in extra-colonic locations.

PMID- 17507895
TI  - Contrast-enhanced ultrasonography in diagnosing liver metastases.
AB  - BACKGROUND: Dual-phase spiral computed tomography (CT) is still the primary
      imaging technique in the diagnosis of focal liver lesions. Contrast-enhanced
      ultrasonography (CEUS) is the most sensitive sonographic technique. The purpose
      of this study was to investigate the efficacy of CEUS in detecting liver
      metastases compared with CT as the standard of reference. MATERIAL/METHODS: The
      examined group consisted of 51 patients (24 men and 27 women, age range: 27-84
      years, mean: 57.4 years) suspected of liver metastases. The routine diagnostic
      approach consisted of B-mode US, CEUS, and CT. Final diagnosis was made at
      cytologic (n=18) or histologic examination (n=14) and in 9 patients by combining
      information from CT scans, medical history, and clinical and biochemical
      investigations. RESULTS: Liver cysts and abscesses were detected in 10 patients.
      They were excluded from the further analyses. In the remaining 41 patients a
      total of 134 metastases were detected. In 15 patients with metastases, US images
      of the liver appeared normal. CEUS detected metastases in 36 patients. The
      sensitivities of the methods per patient were US 63.4% and CEUS 90.2%.
      Sensitivities of the methods per lesion were US 60.9%, CT 77.6%, and CEUS 90.2%.
      Application of contrast media (SonoVue) significantly increased diagnosing of
      liver metastases compared with standard sonography and CT. CONCLUSIONS: CEUS
      increased diagnostic confidence in the detection and characterization of hepatic
      metastases compared with standard sonography. Real-time contrast-enhanced
      sonography is particularly advantageous in detecting small metastases.

PMID- 17507896
TI  - Magnetic resonance imaging as a diagnostic tool in case of ovarian masses in
      girls and young women.
AB  - BACKGROUND: Gynecological examination and transvaginal ultrasound are difficult
      or impossible in girls and young women who have not started their sexual life. CT
      is not a method of choice in this age group because of the ionizing radiation and
      iodine-containing contrast media. MRI is chosen then. MATERIAL/METHODS: Pelvic
      MRI was performed in 15 patients aged 9-19 years with suspected ovarian mass
      after they had had unclear gynecological and sonographic examinations. 1.5 T MRI
      systems were used. SE,T(F)SE and SPIR sequences were applied in T1- and T2
      weighted images in three planes. Contrast media were administered in 7 patients.
      RESULTS: In a group of 3 girls with acute abdominal pain, polycystic ovaries,
      ovarian hemorrhagic cyst, and fibroma of the ovary were diagnosed. In a group of
      11 patients with chronic abdominal pain, dermoid cysts of the ovaries were found
      in 7 cases, in one bilateral and accompanied by ectopic kidney. In 2 patients,
      serous cysts were diagnosed. In 2 cases an ovarian origin of the mass was
      excluded: multilocular cystic lesion in the presacral region and a hydatid mole
      were revealed. A neoplastic ovarian mass was diagnosed in a girl with increasing
      circumference of the abdomen. The accuracy of MRI in localizing lesions was 100%.
      Its accuracy in precisely characterizing lesions was 83.3%. CONCLUSIONS: Magnetic
      resonance imaging, with its noninvasiveness, high spatial resolution, and tissue
      specificity, is a method of choice in the diagnosis or exclusion of ovarian
      pathology in children and adolescents.

PMID- 17507897
TI  - Comparison of thermography and Doppler sonography in the evaluation of the cold
      immersion test in women with excessive vasospastic reaction.
AB  - BACKGROUND: Determining the predisposition to vasospastic reactions in a function
      test is important at the earliest possible stage of diagnosis. Thermography is an
      acknowledged procedure for monitoring function tests; however, its availability
      is limited. The aim of this study was to compare the progression of the cold
      immersion test in a thermal picture and an US-CD examination with the flow
      assessment of the small blood vessels of the hand. MATERIAL/METHODS: A group of
      16 women declaring high cold tolerance of their hands was compared with a group
      of 24 women reporting hand complaints when exposed to the cold. The subjects
      underwent a test in which they immersed their right hand in ice-cold water (0
      degrees C). Then images of the temperature distribution in the hand were recorded
      with a thermovisory camera. At the same time, spectral waveforms were registered
      in the proper palmar digital artery and in the radial artery at specified time
      intervals. RESULTS: Data analysis comprised temperature measurements at the level
      of the nail plate of the middle finger and at the wrist. There were differences
      between the groups at all the stages of the immersion test (efficient return of
      temperature to initial values in the reference group, delayed return in subjects
      with low tolerance to thermal stimuli). Flow resistance analysis using the
      Doppler method in the studied arteries revealed similar differences between the
      groups (swift flow normalization and efficient reperfusion in the reference
      group, higher flow resistance and low reperfusion in subjects with low tolerance
      to thermal stimuli). CONCLUSIONS: Changes in the parameters of hand warmth during
      the immersion test assessed by thermography and changes in the flow parameters
      observed by Doppler sonography demonstrated similar progression, which suggests
      the equivalence of both methods. Doppler sonography may thus serve as a method of
      monitoring function tests to establish a predisposition to vasospasm.

PMID- 17507898
TI  - Digital radiography density measurements in differentiation between periapical
      granulomas and radicular cysts.
AB  - BACKGROUND: The distinction between radicular cysts and apical granulomas is a
      matter of considerable importance in making a treatment decision. Because there
      are no clearly defined radiographic criteria, the distinction is made on the
      grounds of size. However, it has been suggested that cysts can be distinguished
      from granulomas on the basis of their radiometric density. The results of
      previous studies have proved conflicting. To determine possibilities of
      application of digital radiography density measurements in differentiation of
      periapical granulomas and radicular cysts of inflammatory origin.
      MATERIAL/METHODS: The material consisted of 355 digital periapical radiograms
      obtained using Digora, RVG and Dixi 2 digital radiography systems in patients
      aged 20 to 84, divided into two groups: 259 granulomas and 102 radicular cysts.
      By means of Digora 2.0 software there were measured maximum and minimum densities
      along a line, then there was calculated the difference between maximum and
      minimum density. The largest dimensions of the lesions were measured -
      perpendicular and parallel to the root canal axis. RESULTS: It was proved that to
      some extent it was possible to differentiate cystic granulomas and radicular
      cysts on the basis of the difference between maximum and minimum density in
      linear measurement - when the difference exceeded 85.6 the lesion was a cyst and
      when it was below 45.9 a granuloma was diagnosed. CONCLUSIONS: Combination of two
      criteria - the calculated difference between densities and the largest dimension
      of a lesion, increased diagnostic possibilities of radiological differentiation
      of granulomas and radicular cysts.

PMID- 17507899
TI  - Late presenting diaphragmatic hernia: clinical and diagnostic aspects.
AB  - BACKGROUND: The congenital diaphragm hernia presents most frequently in the
      neonatal period. In a small group of children his defect can be diagnosed beyond
      the newborn age, during late infancy or early childhood. The late presenting
      congenital diaphragm hernia is characterized by a variable clinical picture and
      represents a considerable diagnostic challenge. The aim of this study was to
      evaluate the usefulness of imaging methods in diagnosis, monitoring and
      management of late presenting diaphragmatic hernias. MATERIAL/METHODS: The
      retrospective analysis of 58 children with congenital diaphragm hernia, aged from
      1 day to 7.5 years (the average: 2.6 years) treated between 1990-2006 in the
      Department of Pediatric Surgery and Urology of the Medical University of Wroclaw
      was carried out. 19 (39%) children in whom the malformation was recognized beyond
      the newborn period were numbered to this group. The detailed analysis comprised
      the type of clinical manifestation, as well as the therapeutic and diagnostic
      algorithm. RESULTS: The postero-lateral variant of the defect was recognized in
      15 children, the Morgagni type in 2 and the hiatal type in 2. Right-sided hernia
      was found in 4 children, whereas left-sided in 15. 8 infants with left hernia
      presented with dominant symptoms from the respiratory system; 3 infants - from
      the GI tract with delayed somatic growth. Among children over 1 year of age, 6
      presented symptoms of respiratory origin and only 2 of gastrointestinal nature.
      Only one child showed associated congenital malformations. In all children the
      diagnosis was made on the basis of imaging modalities. The GI contrast study was
      decisive imaging method in 14 children, ultrasonography in 15, CT in 4.
      CONCLUSIONS: The lack of typical clinical presentation in cases of late
      presenting CDH leads to delayed diagnosis of the defect. This clinical entity
      should be however taken into account in the differential diagnosis of children
      with respiratory distress and GI disturbances. The imaging studies are essentials
      in every case.

PMID- 17507900
TI  - Low-dose protocol for head CT in monitoring hydrocephalus in children.
AB  - BACKGROUND: Children with hydrocephalus and increased intracranial pressure are
      treated with ventricular shunts. Multiple head CT is used to assess shunt
      malfunction and changes in ventricular size (volume). Because of the naturally
      high contrast of the head structures in CT imaging, a low-dose protocol for
      hydrocephalic pediatric patients was proposed. The aim of the study was to assess
      the implemented protocol in categories of radiation risk to the patients.
      MATERIAL/METHODS: Head CT examinations were performed using the fourth-generation
      single-slice scanner PQ-2000 (Picker). Exposure parameters of the routine head
      procedure stored in the scanner software were the starting point for the
      investigation. The acceptable ranges of the modified parameters were found on the
      basis of earlier published results. The effect of the new protocol on image
      quality was tested using a CATPHAN phantom. The organ doses were evaluated
      experimentally. The clinical images were evaluated by two experienced and
      independent radiologists. RESULTS: Head CT examinations were performed in 380
      children with hydrocephalus during a 10-year period at the Department of
      Diagnostic Imaging Polish Mother's Memorial Hospital. Until 2005 these children
      were examined according to the routine protocol of the scanner, i.e. 10 mm
      contiguous axial, 120 kVp, and 225 mAs. Then the protocol was modified to 10 mm
      contiguous axial, 100 kVp, and 150 mAs. Reductions in patient doses to 70% were
      found while the clinical images maintained sufficient diagnostic value.
      CONCLUSIONS: The low-dose protocol for head CT can be recommended for the
      monitoring of pediatric hydrocephalus patients.

PMID- 17507901
TI  - Coronary computed tomography angiography in patients after percutaneous coronary
      intervention (PCI): focus on post-processing and visualization techniques.
AB  - Coronary stent imaging with computed tomography is challenging because of high
      density artifacts. However, noninvasive coronary angiography with computed
      tomography is gaining acceptance as a valid alternative to cardiac
      catheterization in a broader array of clinical settings, and the work-up of
      patients after coronary stent implantation represents an application of pressing
      clinical utility. Only a minority of patients who develop recurrent chest pain
      after stent implantation have myocardial ischemia, thus a sensitive noninvasive
      study is desirable. With an awareness of the limitations of the technique, the
      systematic application of dedicated strategies of data post-processing and
      display techniques permits partial compensation of the technical limitations
      brought about by metallic struts. ADVANCES IN KNOWLEDGE: 1. The role of coronary
      computed tomography angiography in the diagnostic work-up of patients with
      symptoms after stent placement 2. Systematization of post-processing, display,
      and review techniques for optimal evaluation of coronary stents with coronary
      computed tomography angiography. SUMMARY STATEMENT: The follow-up of patients
      after coronary stenting is an appealing but challenging application of coronary
      computed tomography angiography. The presence of intrinsic limitations requires
      the use of dedicated post-processing and visualization techniques.

PMID- 17507902
TI  - Indirect selection for mutability.

PMID- 17507903
TI  - Selection and the rate of loss of genetic variation: natural selection and
      genetic diversity.

PMID- 17507904
TI  - Cardiac transplantation and cyclosporine nephrotoxicity.

PMID- 17507905
TI  - Gadolinium and nephrogenic systemic fibrosis.
AB  - Nephrogenic systemic fibrosis (NSF) is characterized by red skin areas or plaques
      that over several weeks successively develop to painful thickened skin with a
      'woody' texture, resembling 'peau d'orange'. Starting at the extremities, it may
      spread to the trunk, and may progressively inhibit flexion of adjacent joints. In
      skin biopsies of affected areas, thickened collagen bundles, mucin deposition,
      and proliferation of fibroblasts and elastic fibers are seen. Originally
      described as nephrogenic fibrosing dermopathy (NFD) because of its primarily
      cutaneous manifestation, this entity was then named NSF because of systemic
      involvement of other organs like lungs, myocardium, or striated muscles. The
      pathogenesis of the disease is not yet known, but our observations suggest a
      close association between development of NSF and exposure to gadolinium
      containing contrast agents, thereafter confirmed by other authors. Recently,
      gadolinium was demonstrated to be detectable in skin tissue samples of affected
      patients. In this short review, the development of NSF and its sequential
      association with the exposure to gadolinium-containing contrast agents is
      presented. The mechanisms likely to cause NFD/NSF are discussed.

PMID- 17507906
TI  - Exogenous mesenchymal stem cells localize to the kidney by means of CD44
      following acute tubular injury.
AB  - Mesenchymal stem cells (MSC) were recently shown to migrate to injured tissues
      when transplanted systemically. The mechanisms underlying the migration and
      homing of these cells is, however, unclear. In this study, we examine the role of
      CD44 and its major ligand, hyaluronic acid, in the trafficking of intravenously
      injected MSC in the glycerol-induced mouse model of acute renal failure (ARF). In
      vitro, hyaluronic acid promoted a dose-dependent migration of the stem cells that
      was inhibited by an anti-CD44 blocking monoclonal antibody. In vivo, stem cells
      injected into mice with ARF migrated to the injured kidney where hyaluronic acid
      expression was increased. Their presence correlated with morphological and
      functional recovery. Renal localization of the MSC was blocked by pre-incubation
      with the CD44 blocking antibody or by soluble hyaluronic acid. Stem cells derived
      from CD44 knockout mice did not localize to the injured kidney and did not
      accelerate morphological or functional recovery. Reconstitution by transfection
      of CD44 knockout stem cells with cDNA encoding wild-type CD44, but not a loss of
      function CD44 unable to bind hyaluronic acid, restored in vitro migration and in
      vivo localization of the cells to injured kidneys. We suggest that CD44 and
      hyaluronic acid interactions recruit exogenous MSC to injured renal tissue and
      enhance renal regeneration.

PMID- 17507907
TI  - Community-based incidence of acute renal failure.
AB  - There is limited information about the true incidence of acute renal failure
      (ARF). Most studies could not quantify disease frequency in the general
      population as they are hospital-based and confounded by variations in threshold
      and the rate of hospitalization. Earlier studies relied on diagnostic codes to
      identify non-dialysis requiring ARF. These underestimated disease incidence since
      the codes have low sensitivity. Here we quantified the incidence of non-dialysis
      and dialysis-requiring ARF among members of a large integrated health care
      delivery system - Kaiser Permanente of Northern California. Non-dialysis
      requiring ARF was identified using changes in inpatient serum creatinine values.
      Between 1996 and 2003, the incidence of non-dialysis requiring ARF increased from
      322.7 to 522.4 whereas that of dialysis-requiring ARF increased from 19.5 to 29.5
      per 100,000 person-years. ARF was more common in men and among the elderly,
      although those aged 80 years or more were less likely to receive acute dialysis
      treatment. We conclude that the use of serum creatinine measurements to identify
      cases of non-dialysis requiring ARF resulted in much higher estimates of disease
      incidence compared with previous studies. Both dialysis-requiring and non
      dialysis requiring ARFs are becoming more common. Our data underscore the public
      health importance of ARF.

PMID- 17507908
TI  - 1,25-Dihydroxyvitamin D3 targeting of NF-kappaB suppresses high glucose-induced
      MCP-1 expression in mesangial cells.
AB  - Macrophages accumulate in kidney glomeruli and interstitium of patients with
      diabetic nephropathy in response to monocyte chemoattractant protein-1 (MCP-1); a
      chemokine produced by both tubular epithelial and mesangial cells (MCs). Vitamin
      D and its analogs have been shown to have renoprotective effects; however, there
      are few studies involving diabetic nephropathy. We explored mechanisms by which
      1,25-dihydroxyvitamin D3 (1,25(OH)2D3) can be renoprotective by measuring MCP-1
      expression in MCs. Using a luciferase reporter assay, we found that high glucose
      (HG)-induced MCP-1 transcription and that this induction is blocked by
      1,25(OH)2D3. Electrophoretic mobility shift and chromatin immunoprecipitation
      assays showed that HG increased the p65/p50 binding to the two NF-kappaB sites
      within the promoter. This was suppressed by 1,25(OH)2D3, but this decrease was
      reversed by overexpression of p65. 1,25(OH)2D3 was found to stabilize
      IkappaBalpha leading to an inhibition of p65 translocation to the nucleus and
      subsequent reduction of NF-kappaB binding. In primary MCs prepared from vitamin D
      receptor knockout animals, basal MCP-1 levels were elevated but not affected by
      1,25(OH)2D3. The analog paricalcitol inhibited the induction and activity of MCP
      1 while ameliorating glomerulosclerosis in streptozotocin-diabetic mice. Our
      results suggest that 1,25(OH)2D3 might block hyperglycemia-induced renal injury
      by blunting NF-kappaB activation.

PMID- 17507909
TI  - Alcohol badly affects eye movements linked to steering, providing for automatic
      in-car detection of drink driving.
AB  - Driving is a classic example of visually guided behavior in which the eyes move
      before some other action. When approaching a bend in the road, a driver looks
      across to the inside of the curve before turning the steering wheel. Eye and
      steering movements are tightly linked, with the eyes leading, which allows the
      parts of the brain that move the eyes to assist the parts of the brain that
      control the hands on the wheel. We show here that this optimal relationship
      deteriorates with levels of breath alcohol well within the current UK legal limit
      for driving. The eyes move later, and coordination reduces. These changes lead to
      bad performance and can be detected by an automated in-car system, which warns
      the driver is no longer fit to drive.

PMID- 17507910
TI  - Decreased mRNA expression of netrin-G1 and netrin-G2 in the temporal lobe in
      schizophrenia and bipolar disorder.
AB  - The membrane-bound axon guidance molecules netrin-G1 (NTNG1) and netrin-G2
      (NTNG2) play a role in synaptic formation and maintenance. Non-coding single
      nucleotide polymorphisms (SNPs) in both genes have been reported to be associated
      with schizophrenia. The main aim of this study was to determine if NTNG1 and
      NTNG2 mRNA expression is altered in schizophrenia or bipolar disorder, and/or
      influenced by disease-associated SNPs. NTNG1 and NTNG2 mRNAs were examined in the
      medial and inferior temporal lobe using in situ hybridization and RT-PCR in the
      Stanley Medical Research Institute array collection, and in rat hippocampus
      during development and after antipsychotic administration. NTNG1 mRNA isoforms
      were also examined during human brain development. For NTNG1, the G1c isoform was
      reduced in bipolar disorder and with a similar trend in schizophrenia; expression
      of four other NTNG1 isoforms was unchanged. In both schizophrenia and bipolar
      disorder, NTNG2 mRNA was reduced in CA3, with reductions also found in CA4 and
      perirhinal cortex in bipolar disorder. The SNPs did not affect NTNG1 or NTNG2
      mRNA expression. Both NTNG1 and NTNG2 mRNAs were developmentally regulated, and
      were unaltered by haloperidol, but NTNG2 mRNA was modestly increased by
      clozapine. These data implicate NTNG1 and NTNG2 in the pathophysiology of
      schizophrenia and bipolar disorder, but do not support the hypothesis that
      altered mRNA expression is the mechanism by which genetic variation of NTNG1 or
      NTNG2 may confer disease susceptibility.

PMID- 17507911
TI  - Markers in the 5'-region of GABRG1 associate to alcohol dependence and are in
      linkage disequilibrium with markers in the adjacent GABRA2 gene.
AB  - Following an initial report, there have been multiple replications of an
      association of alcohol dependence (AD) to markers within a haplotype block that
      includes the 3'-half of the gene encoding the GABA(A) alpha-2 subunit (GABRA2),
      on chromosome 4p. We examined the intergenic extent of this haplotype block and
      the association to AD of markers in the adjacent 5' haplotype block in GABRG1,
      which encodes the GABA(A) receptor gamma-1 subunit. We genotyped 15 single
      nucleotide polymorphisms in the GABRG1-GABRA2 interval as well as at 34 ancestry
      informative markers in three samples: 435 AD and 635 screened control subjects
      from Connecticut and 812 participants from a multicenter AD treatment trial. We
      observed two large haplotype blocks in the GABRG1-GABRA2 intergenic interval with
      a region of increased recombination midway between the two genes. Markers in the
      two haplotype blocks were in moderate linkage disequilibrium. Compared with
      markers in the GABRA2 haplotype block, markers in the 5' GABRG1 haplotype showed
      greater allelic, genotypic and haplotypic association with AD in European
      Americans from both AD samples. Logistic regression analysis indicated that
      genetic elements in the GABRG1 haplotype block likely contribute to AD risk in an
      additive manner, whereas those in the GABRA2 haplotype block may act in a
      dominant manner in relation to risk of AD.

PMID- 17507912
TI  - Effects of smoking successive low- and high-nicotine cigarettes on hypothalamic
      pituitary-adrenal axis hormones and mood in men.
AB  - Smoking one cigarette produces rapid nicotine dose-related increases in
      hypothalamic-pituitary-adrenal (HPA) axis hormones, mood, and heart rate, but
      relatively little is known about the effects of smoking several cigarettes
      successively. Twenty-four healthy adult men who met Diagnostic and Statistical
      Manual of Mental Disorders, fourth edition (DSM-IV) criteria for nicotine
      dependence provided informed consent. After overnight abstinence from smoking,
      men smoked three low- or high-nicotine cigarettes for 4 min each at 60 min
      intervals. Samples for nicotine and hormone analysis, Visual Analog Scale (VAS)
      ratings of subjective effects and heart rate were collected at 4, 8, 12, 16, 20,
      30, 40, and 50 min after each cigarette. After low-nicotine cigarettes, nicotine
      levels, adrenocorticotropin hormone, and heart rate did not increase
      significantly, cortisol and dehydroepiandrosterone decreased significantly, and
      positive VAS ratings were lower but parallel to ratings after high-nicotine
      cigarette smoking. After high-nicotine cigarettes, peak nicotine levels increased
      monotonically. HPA axis hormones increased after smoking, but peak levels did not
      differ significantly after successive high-nicotine cigarettes. Positive VAS
      ratings and heart rate increased after each high-nicotine cigarette, but peak
      levels were lower after smoking the second and third cigarette. 'Craving'
      decreased significantly after smoking both low- and high-nicotine cigarettes,
      then gradually increased during the 60 min interval between cigarettes. These
      data are consistent with clinical reports that the first cigarette after
      overnight nicotine abstinence is most salient. Tolerance to the subjective and
      cardiovascular effects of nicotine developed rapidly during repeated cigarette
      smoking, but nicotine-stimulated increases in HPA axis hormones did not change
      significantly.

PMID- 17507913
TI  - Nicotine self-administration, extinction responding and reinstatement in
      adolescent and adult male rats: evidence against a biological vulnerability to
      nicotine addiction during adolescence.
AB  - Initiation of smoking behavior typically occurs during adolescence and rarely
      occurs during adulthood. Despite this epidemiological evidence, relatively little
      is known about possible neurobiological differences in the response to nicotine
      in adolescents that might make them more vulnerable to nicotine addiction. In the
      current study, we assessed nicotine self-administration under fixed ratio (FR)
      and progressive ratio (PR) reinforcement schedules in adolescent (postnatal day
      (P) 33-35) and adult (P91-94) rats. We then assessed extinction and reinstatement
      of nicotine seeking in adulthood in rats that initiated nicotine self
      administration during either adolescence or adulthood. Nicotine self
      administration (0.03 mg/kg/infusion, i.v.) was higher in adult rats than in
      adolescent rats under FR5 and PR reinforcement schedules; no age differences in
      nicotine self-administration were observed under FR1 or FR2 reinforcement
      schedules. In contrast, saccharin self-administration under FR5 and PR
      reinforcement schedules was similar in both age groups, potentially ruling out
      age differences in general performance. Rats that initiated nicotine self
      administration as adults demonstrated a greater resistance to extinction of
      nicotine taking behavior when saline was substituted for nicotine than rats that
      initiated self-administration as adolescents. Reinstatement of nicotine seeking
      following nicotine priming injections (0.075, 0.15, 0.3 mg/kg, s.c.) was
      independent of the age of onset of nicotine self-administration. The present data
      from established rat models of drug self-administration and drug relapse suggest
      that nicotine is less reinforcing in adolescent compared with adult rats and that
      processes other than the reinforcing effects of nicotine may be involved in the
      greater susceptibility to smoking during the adolescent developmental stage.

PMID- 17507914
TI  - Abnormal fear conditioning and amygdala processing in an animal model of autism.
AB  - A core feature of autism spectrum disorders is the impairment in social
      interactions. Among other brain regions, a deficit in amygdala processing has
      been suggested to underlie this impairment, but whether the amygdala is
      processing fear abnormally in autism, is yet not clear. We used the valproic acid
      (VPA) rat model of autism to (a) screen for autism-like symptoms in rats, (b)
      test for alterations in amygdala-dependent fear processing, and (c) evaluate
      neuronal reactivity and synaptic plasticity in the lateral amygdala by means of
      in vitro single-cell electrophysiological recordings. VPA-treated animals
      displayed several symptoms common to autism, among them impaired social
      interactions and increased repetitive behaviors. Furthermore, VPA-treated rats
      were more anxious and exhibited abnormally high and longer lasting fear memories,
      which were overgeneralized and harder to extinguish. On the cellular level, the
      amygdala was hyperreactive to electrical stimulation and displayed boosted
      synaptic plasticity as well as a deficit in inhibition. We show for the first
      time enhanced, overgeneralized and resistant conditioned fear memories in an
      animal model of autism. Such hyperfear could be caused by the hyperreactivity and
      hyperplasticity found in the lateral amygdala, which may in turn be due to a
      deficit in the inhibitory system of the amygdala. We hypothesize an 'aversive
      world' syndrome that could, even if not a primary cause of the disorder itself,
      underlie some core symptoms in autism, such as impairments in social interactions
      and resistance to rehabilitation.

PMID- 17507915
TI  - Effects of estradiol on cocaine self-administration and cocaine discrimination by
      female rhesus monkeys.
AB  - The ovarian steroid hormone, estradiol, enhances the reinforcing and locomotor
      activating effects of cocaine in rodents under some conditions. The present study
      evaluated the acute effects of estradiol benzoate (E(2)beta) on cocaine self
      administration and cocaine discrimination in female rhesus monkeys. Cocaine self
      administration (0.10 mg/kg/inj., i.v.) was maintained on a fixed-ratio (FR) 30
      schedule of reinforcement, and monkeys had access to cocaine during one 2-h
      session each day. E(2)beta in a cyclodextrin vehicle (0.00001-0.01 mg/kg, i.m.)
      was administered 30 min before test sessions conducted twice each week. Cocaine
      doses were administered in an irregular order during each dose-effect curve
      determination (0.001-0.3 mg/kg/inj.). Blood samples were collected after test
      sessions to determine 17beta-estradiol levels. Banana-flavored food pellets were
      available on an FR 30 schedule in three 1-h sessions each day. Five monkeys were
      trained to discriminate cocaine (0.18 mg/kg, i.m.) from saline in a two-key food
      reinforced procedure, and the effects of pretreatment with E(2)beta in
      cyclodextrin and in sesame oil were studied. Acute administration of E(2)beta did
      not consistently alter the cocaine self-administration or drug discrimination
      dose-effect curves in comparison to saline control treatment. Females also did
      not self-administer E(2)beta (0.00001-0.10 mg/kg, i.v.) above saline levels.
      Finally, E(2)beta (0.0001-0.01 mg/kg, i.m.) did not substitute for cocaine in
      monkeys trained to discriminate cocaine from saline. Taken together, these data
      suggest that over the dose range studied, estradiol administration does not
      consistently alter the abuse-related effects of cocaine in female rhesus monkeys.

PMID- 17507916
TI  - Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported
      depressive symptoms in adolescence: a prospective study on the fetal origins of
      depressed mood.
AB  - Depressive symptomatology can proceed from altered hypothalamic-pituitary
      adrenocortex (HPA)-axis function. Some authors stress the role that early life
      stress (ELS) may play in the pathophysiology of depressive symptoms. However, the
      involvement of the HPA-axis in linking prenatal ELS with depressive symptoms has
      not been tested in a prospective-longitudinal study extending until after puberty
      in humans. Therefore, we examined whether antenatal maternal anxiety is
      associated with disturbances in HPA-axis regulation and whether the HPA-axis
      dysregulation mediates the association between antenatal maternal anxiety and
      depressive symptoms in post-pubertal adolescents. As part of a prospective
      longitudinal study, we investigated maternal anxiety at 12-22, 23-32, and 32-40
      weeks of pregnancy (wp) with the State Trait Anxiety Inventory (STAI). In the 14
      15-year-old offspring (n=58) HPA-axis function was measured through establishing
      a saliva cortisol day-time profile. Depressive symptoms were measured with the
      Children's Depression symptoms Inventory (CDI). Results of regression analyses
      showed that antenatal exposure to maternal anxiety at 12-22 wp was in both sexes
      associated with a high, flattened cortisol day-time profile (P=0.0463) which, in
      female adolescents only, was associated with depressive symptoms (P=0.0077). All
      effects remained after controlling for maternal smoking, birth weight,
      obstetrical optimality, maternal postnatal anxiety and puberty phase. Our
      prospective study demonstrates, for the first time, the involvement of the HPA
      axis in the link between antenatal maternal anxiety/prenatal ELS and depressive
      symptoms for post-pubertal female adolescents.

PMID- 17507917
TI  - Clozapine normalizes prefrontal cortex dopamine transmission in monkeys
      subchronically exposed to phencyclidine.
AB  - The mechanism responsible for the therapeutic effects of the prototypical
      atypical antipsychotic drug, clozapine, is still not understood; however, there
      is persuasive evidence from in vivo studies in normal rodents and primates that
      the ability to elevate dopamine neurotransmission preferentially in the
      prefrontal cortex is a key component to the beneficial effects of clozapine in
      schizophrenia. Theoretically, such an effect of clozapine would counteract the
      deficient dopaminergic innervation of the prefrontal cortex that appears to be
      part of the pathophysiology of schizophrenia. We have previously shown that
      following repeated, intermittent administrations of phencyclidine to monkeys
      there is lowered prefrontal cortical dopamine transmission and impairment of
      cognitive performance that is dependent on the prefrontal cortex; these
      biochemical and behavioral changes therefore model certain aspects of
      schizophrenia. We now investigate the effects of clozapine on the dopamine
      projections to prefrontal cortex, nucleus accumbens, and striatum in control
      monkeys and in those withdrawn from repeated phencyclidine treatment, using a
      dose regimen of clozapine that ameliorates the cognitive deficits described in
      the primate phencyclidine (PCP) model. In normal monkeys, clozapine elevated
      dopamine turnover in all prefrontal cortical, but not subcortical, regions
      analyzed. In the primate PCP model, clozapine normalized dopamine (DA) turnover
      in the dorsolateral prefrontal cortex, prelimbic cortex, and cingulate cortex.
      Thus, the present data support the hypothesis that the therapeutic effects of
      clozapine in this primate model and perhaps in schizophrenia may be related at
      least in part to the restoration of DA tone in the prefrontal cortex.

PMID- 17507918
TI  - Ovarian steroid treatment decreases corticotropin-releasing hormone (CRH) mRNA
      and protein in the hypothalamic paraventricular nucleus of ovariectomized
      monkeys.
AB  - Corticotropin-releasing hormone (CRH) gene and protein expression were examined
      in the paraventricular nucleus (PVN) of ovariectomized female macaques treated
      with placebo or hormone therapy (HT) consisting of either estrogen (E) for 28
      days, or progesterone (P) for the last 14 of 28 days, or E for 28 days
      supplemented with P for the last 14 of 28 days using Silastic capsules implanted
      s.c. in the periscapular region (n=4/group). Perfusion fixed sections (25 microm)
      at five levels of the PVN (rostral to caudal at 250 microm intervals) were
      immunostained (ICC) with an antibody to human CRH or processed in an in situ
      hybridization (ISH) assay with a monkey specific CRH riboprobe. The immunostained
      CRH-positive area was quantified with a Marianas Stereology Workstation and
      Slidebook 4.2. There was a significant decrease in the immunological CRH signal
      with E, P, and E+P treatment as measured by total or average pixels and microns
      (analysis of variance (ANOVA), p<0.002; Student-Newman-Keul's post hoc test
      versus placebo control group, p<0.05). There was also a decrease in the number of
      detectable CRH neurons (ANOVA, p<0.03) with HT. The sections processed for ISH
      were exposed to autoradiographic films. The CRH mRNA signal was analyzed with NIH
      Image. The average optical density and positive pixel area of the CRH mRNA signal
      was significantly suppressed by ovarian HT (ANOVA p<0.002; Student-Newman-Keul's
      post hoc test versus placebo control group, p<0.05). In summary, 1 month of
      stable treatment with a moderate dose of E, P or E+P significantly reduced CRH
      mRNA and protein in the PVN of ovariectomized monkeys. These results suggest that
      this hormone treatment regimen may increase stress resilience in surgically
      menopausal primates.

PMID- 17507919
TI  - Chronic morphine selectively impairs cued fear extinction in rats: implications
      for anxiety disorders associated with opiate use.
AB  - Previous studies have shown that opioid transmission plays an important role in
      learning and memory. However, little is known about the course of opiate
      associated learning and memory deficits after cessation of chronic opiate use in
      a behavioral animal model. In the present study, we examined the effects of
      chronic morphine on fear extinction, an important preclinical model for behavior
      therapy of human anxiety disorders. Rats were administrated subcutaneously
      morphine hydrochloride or saline twice per day for continuous 10 days. Rats
      received a cued or contextual fear conditioning session 7 days after the last
      morphine injection. During subsequent days, rats received four cued or contextual
      extinction sessions (one session per day). Percent freezing was assessed during
      all phases of training. Chronic morphine did not affect the acquisition of cued
      fear response or the initial encoding of extinction memory within each session,
      but produced an impairment in the between-session extinction. However, the same
      morphine treatment schedule did not affect the acquisition or extinction of
      contextual fear response. These results suggest that the effects of chronic
      morphine on memory for fear extinction are complex. Chronic morphine selectively
      impairs extinction of cued fear response. This deficit in fear extinction may be
      one of those critical components that contribute to the high prevalence of
      anxiety disorders in opiate addicts.

PMID- 17507920
TI  - Preclinical predictors of clinical safety: opportunities for improvement.
AB  - Toxicology studies in animals are required by regulatory authorities worldwide to
      provide assurances that clinical testing of pharmaceutical candidates can be
      conducted safely. Safety concerns from animal studies account for over 20% of
      attritions from drug development. As discordance between humans and animals is
      expected, two goals of safe and efficient drug development must be (1) to improve
      the human relevance of animal testing with new models and technologies, and (2)
      to advance quickly to clinical testing armed with improved safety biomarker
      tools.

PMID- 17507922
TI  - An evaluation of computer-aided disproportionality analysis for post-marketing
      signal detection.
AB  - To understand the value of computer-aided disproportionality analysis (DA) in
      relation to current pharmacovigilance signal detection methods, four products
      were retrospectively evaluated by applying an empirical Bayes method to Merck's
      post-marketing safety database. Findings were compared with the prior detection
      of labeled post-marketing adverse events. Disproportionality ratios (empirical
      Bayes geometric mean lower 95% bounds for the posterior distribution (EBGM05))
      were generated for product-event pairs. Overall (1993-2004 data, EBGM05> or =2,
      individual terms) results of signal detection using DA compared to standard
      methods were sensitivity, 31.1%; specificity, 95.3%; and positive predictive
      value, 19.9%. Using groupings of synonymous labeled terms, sensitivity improved
      (40.9%). More of the adverse events detected by both methods were detected
      earlier using DA and grouped (versus individual) terms. With 1939-2004 data,
      diagnostic properties were similar to those from 1993 to 2004. DA methods using
      Merck's safety database demonstrate sufficient sensitivity and specificity to be
      considered for use as an adjunct to conventional signal detection methods.

PMID- 17507921
TI  - Quantitative imaging and sigmoidoscopy to assess distribution of rectal
      microbicide surrogates.
AB  - Understanding the distribution of microbicide and human immunodeficiency virus
      (HIV) within the gastrointestinal tract is critical to development of rectal HIV
      microbicides. A hydroxyethylcellulose-based microbicide surrogate or viscosity
      matched semen surrogate, labeled with gadolinium-DTPA (diethylene triamine
      pentaacetic acid) and 99mTechnetium-sulfur colloid, was administered to three
      subjects under varying experimental conditions to evaluate effects of enema,
      coital simulation, and microbicide or semen simulant over 5 h duration.
      Quantitative assessment used single photon emission computed tomography
      (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging,
      and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all
      studies by a median (interquartile range) of 50% (29-102%; P<0.001), as far as
      the splenic flexure (approximately 60 cm) in 12% of studies. There was a
      correlation in concentration profile between endoscopic sampling and SPECT
      assessments. HIV-sized particles migrate retrograde, 60 cm in some studies, 4 h
      after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be
      used quantitatively to facilitate rational development of microbicides for rectal
      use.

PMID- 17507923
TI  - A positron emission tomography study to assess binding of lecozotan, a novel 5
      hydroxytryptamine-1A silent antagonist, to brain 5-HT1A receptors in healthy
      young and elderly subjects, and in patients with Alzheimer's disease.
AB  - This positron emission tomography (PET) study was conducted to assess binding of
      lecozotan, a new potent and silent 5-hydroxytryptamine-1A (5-HT1A) antagonist
      being developed for the treatment of Alzheimer's disease (AD), to 5-HT1A
      receptors in the human brain using 11C-labeled WAY-100635. Lecozotan was
      administered as a single dose of 0.5, 1, or 5 mg to young subjects and 5 mg to
      elderly subjects and AD patients. PET measurements were performed at 3-4 time
      points over a 25-h period. Mean peak 5-HT1A receptor occupancy (RO) in young
      subjects (seen at 1 h) was 10%, 18%, and 44% for the three doses, respectively.
      Mean peak RO was slightly higher in elderly (63%) and AD patients (55%). An Emax
      pharmacokinetic/pharmacodynamic model adequately described the lecozotan plasma
      concentration-RO relationship. Steady-state peak RO is predicted to be
      approximately 70% for 5 mg q12 h (twice-daily). Results demonstrate that
      lecozotan binds to the human brain 5-HT1A receptors and has a maximum observed RO
      of 50-60% following a single dose of 5 mg in elderly subjects/AD patients.

PMID- 17507924
TI  - Tumor necrosis factor-alpha antagonism improves endothelial dysfunction in
      patients with Crohn's disease.
AB  - This study assessed the presence of endothelial dysfunction in patients with
      inflammatory bowel diseases (IBDs) and evaluated the possible role of tumor
      necrosis factor (TNF)-alpha in the pathophysiology of this abnormality. Similar
      elevations in circulating markers of inflammation (C-reactive protein and
      interleukin-6) were observed in Crohn's disease and ulcerative colitis compared
      to controls. Endothelium-dependent vasodilation to acetylcholine was impaired in
      Crohn's disease, but not in ulcerative colitis. Endothelium-independent
      vasodilation to sodium nitroprusside, by contrast, was not different among the
      three groups. The TNF-alpha neutralizing antibody, infliximab, enhanced the
      responsiveness to acetylcholine, but not to nitroprusside, in Crohn's disease,
      without modifying vascular responses to both drugs in ulcerative colitis. In
      conclusion, despite comparable degrees of systemic inflammation in the two IBDs,
      endothelial dysfunction is a selective feature of Crohn's disease and is
      beneficially affected by intravascular TNF-alpha neutralization. These findings
      underscore the role of selective cytokine targeting in improving endothelial
      function in patients with Crohn's disease.

PMID- 17507925
TI  - Using disease progression models as a tool to detect drug effect.
AB  - Generally, information required for approval of new drugs is dichotomous in that
      the drug is either efficacious and safe or not. Consequently, the purpose of most
      confirmatory clinical trials is to test the null hypothesis. The primary reasons
      for designing hypothesis testing trials are to provide the information required
      for approval using analyses techniques that are relatively straightforward and
      free of apparent assumptions. However, the information required for approval is
      very different from that used by prescribers for decision making. In the clinic,
      decisions must be made about dose adjustment for individual patients in the
      presence of additional therapies and co-morbidities. Choice of drug and dosing
      regimen is therefore a classical risk to benefit decision that is often poorly
      informed from the results of confirmatory trials. Therefore, providing answers to
      the more difficult question of how to use the drug in a clinical setting is
      essential.

PMID- 17507926
TI  - Disease ecology: the silence of the robins.

PMID- 17507927
TI  - Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation.
AB  - MicroRNAs (miRs) inhibit protein synthesis by mechanisms that are as yet
      unresolved. We developed a cell-free system from Drosophila melanogaster embryos
      that faithfully recapitulates miR2-mediated translational control by means of the
      3' untranslated region of the D. melanogaster reaper messenger RNA. Here we show
      that miR2 inhibits translation initiation without affecting mRNA stability.
      Surprisingly, miR2 induces the formation of dense (heavier than 80S) miRNPs
      ('pseudo-polysomes') even when polyribosome formation and 60S ribosomal subunit
      joining are blocked. An mRNA bearing an ApppG instead of an m7GpppG cap structure
      escapes the miR2-mediated translational block. These results directly show the
      inhibition of m7GpppG cap-mediated translation initiation as the mechanism of
      miR2 function, and uncover pseudo-polysomal messenger ribonucleoprotein
      assemblies that may help to explain earlier findings.

PMID- 17507928
TI  - 8-oxo-guanine bypass by human DNA polymerases in the presence of auxiliary
      proteins.
AB  - Specialized DNA polymerases (DNA pols) are required for lesion bypass in human
      cells. Auxiliary factors have an important, but so far poorly understood, role.
      Here we analyse the effects of human proliferating cell nuclear antigen (PCNA)
      and replication protein A (RP-A) on six different human DNA pols--belonging to
      the B, Y and X classes--during in vitro bypass of different lesions. The
      mutagenic lesion 8-oxo-guanine (8-oxo-G) has high miscoding potential. A major
      and specific effect was found for 8-oxo-G bypass with DNA pols lambda and eta.
      PCNA and RP-A allowed correct incorporation of dCTP opposite a 8-oxo-G template
      1,200-fold more efficiently than the incorrect dATP by DNA pol lambda, and 68
      fold by DNA pol eta, respectively. Experiments with DNA-pol-lambda-null cell
      extracts suggested an important role for DNA pol lambda. On the other hand, DNA
      pol iota, together with DNA pols alpha, delta and beta, showed a much lower
      correct bypass efficiency. Our findings show the existence of an accurate
      mechanism to reduce the deleterious consequences of oxidative damage and, in
      addition, point to an important role for PCNA and RP-A in determining a
      functional hierarchy among different DNA pols in lesion bypass.

PMID- 17507929
TI  - MicroRNA silencing through RISC recruitment of eIF6.
AB  - MicroRNAs (miRNAs) are a class of small RNAs that act post-transcriptionally to
      regulate messenger RNA stability and translation. To elucidate how miRNAs mediate
      their repressive effects, we performed biochemical and functional assays to
      identify new factors in the miRNA pathway. Here we show that human RISC (RNA
      induced silencing complex) associates with a multiprotein complex containing
      MOV10--which is the homologue of Drosophila translational repressor Armitage--and
      proteins of the 60S ribosome subunit. Notably, this complex contains the anti
      association factor eIF6 (also called ITGB4BP or p27BBP), a ribosome inhibitory
      protein known to prevent productive assembly of the 80S ribosome. Depletion of
      eIF6 in human cells specifically abrogates miRNA-mediated regulation of target
      protein and mRNA levels. Similarly, depletion of eIF6 in Caenorhabditis elegans
      diminishes lin-4 miRNA-mediated repression of the endogenous LIN-14 and LIN-28
      target protein and mRNA levels. These results uncover an evolutionarily conserved
      function of the ribosome anti-association factor eIF6 in miRNA-mediated post
      transcriptional silencing.

PMID- 17507930
TI  - West Nile virus emergence and large-scale declines of North American bird
      populations.
AB  - Emerging infectious diseases present a formidable challenge to the conservation
      of native species in the twenty-first century. Diseases caused by introduced
      pathogens have had large impacts on species abundances, including the American
      chestnut, Hawaiian bird species and many amphibians. Changes in host population
      sizes can lead to marked shifts in community composition and ecosystem
      functioning. However, identifying the impacts of an introduced disease and
      distinguishing it from other forces that influence population dynamics (for
      example, climate) is challenging and requires abundance data that extend before
      and after the introduction. Here we use 26 yr of Breeding Bird Survey (BBS) data
      to determine the impact of West Nile virus (WNV) on 20 potential avian hosts
      across North America. We demonstrate significant changes in population
      trajectories for seven species from four families that concur with a priori
      predictions and the spatio-temporal intensity of pathogen transmission. The
      American crow population declined by up to 45% since WNV arrival, and only two of
      the seven species with documented impact recovered to pre-WNV levels by 2005. Our
      findings demonstrate the potential impacts of an invasive species on a diverse
      faunal assemblage across broad geographical scales, and underscore the complexity
      of subsequent community response.

PMID- 17507934
TI  - Health cheques.

PMID- 17507935
TI  - Never had it so good?

PMID- 17507936
TI  - Blurred vision.

PMID- 17507938
TI  - Modellers seek reason for low retraction rates.

PMID- 17507939
TI  - United Nations shelves action on indoor hazards.

PMID- 17507940
TI  - India struggles to find director for top research agency.

PMID- 17507941
TI  - Purdue dogged by misconduct claims.

PMID- 17507942
TI  - Anger at 'unfit' museum design.

PMID- 17507943
TI  - Canadian government pushed to protect land.

PMID- 17507944
TI  - Rules tightened for aboriginal studies.

PMID- 17507945
TI  - Time runs short for HapMap.

PMID- 17507946
TI  - Applicants challenge male order at Howard Hughes.

PMID- 17507950
TI  - Digging deep.

PMID- 17507953
TI  - Biomedical philanthropy: state of the donation.

PMID- 17507955
TI  - Biomedical philanthropy: love or money.

PMID- 17507956
TI  - Biomedical philanthropy: the giving machine. Tadataka Yamada interviewed by Lucy
      Odling-Smee.

PMID- 17507957
TI  - Archaeology: blast in the past?

PMID- 17507958
TI  - Ground-breaking stem-cell work has been reproduced.

PMID- 17507959
TI  - Recognition could support a science code of conduct.

PMID- 17507960
TI  - Animal-welfare section in papers would be a burden.

PMID- 17507961
TI  - Expand free journal project so poor countries can share their valuable climate
      data.

PMID- 17507967
TI  - Optics: beyond diffraction.

PMID- 17507966
TI  - Regenerative biology: new hair from healing wounds.

PMID- 17507968
TI  - Economic ecology: in the market for minke whales.

PMID- 17507969
TI  - Spintronics: silicon twists.

PMID- 17507970
TI  - Organic chemistry: molecular cross-talk.

PMID- 17507972
TI  - Genetics: run, whippet, run.

PMID- 17507973
TI  - Plant development: parental conflict overcome.

PMID- 17507974
TI  - Planetary science: cracks under stress.

PMID- 17507975
TI  - Origins of major human infectious diseases.
AB  - Many of the major human infectious diseases, including some now confined to
      humans and absent from animals, are 'new' ones that arose only after the origins
      of agriculture. Where did they come from? Why are they overwhelmingly of Old
      World origins? Here we show that answers to these questions are different for
      tropical and temperate diseases; for instance, in the relative importance of
      domestic animals and wild primates as sources. We identify five intermediate
      stages through which a pathogen exclusively infecting animals may become
      transformed into a pathogen exclusively infecting humans. We propose an
      initiative to resolve disputed origins of major diseases, and a global early
      warning system to monitor pathogens infecting individuals exposed to wild
      animals.

PMID- 17507976
TI  - Shear heating as the origin of the plumes and heat flux on Enceladus.
AB  - Enceladus, a small icy satellite of Saturn, has active plumes jetting from
      localized fractures ('tiger stripes') within an area of high heat flux near the
      south pole. The plume characteristics and local high heat flux have been ascribed
      either to the presence of liquid water within a few tens of metres of the
      surface, or the decomposition of clathrates. Neither model addresses how delivery
      of internal heat to the near-surface is sustained. Here we show that the most
      likely explanation for the heat and vapour production is shear heating by tidally
      driven lateral (strike-slip) fault motion with displacement of approximately 0.5
      m over a tidal period. Vapour produced by this heating may escape as plumes
      through cracks reopened by the tidal stresses. The ice shell thickness needed to
      produce the observed heat flux is at least 5 km. The tidal displacements required
      imply a Love number of h2 > 0.01, suggesting that the ice shell is decoupled from
      the silicate interior by a subsurface ocean. We predict that the tiger-stripe
      regions with highest relative temperatures will be the lower-latitude branch of
      Damascus, Cairo around 60 degrees W longitude and Alexandria around 150 degrees W
      longitude.

PMID- 17507977
TI  - Eruptions arising from tidally controlled periodic openings of rifts on
      Enceladus.
AB  - In 2005, plumes were detected near the south polar region of Enceladus, a small
      icy satellite of Saturn. Observations of the south pole revealed large rifts in
      the crust, informally called 'tiger stripes', which exhibit higher temperatures
      than the surrounding terrain and are probably sources of the observed eruptions.
      Models of the ultimate interior source for the eruptions are under consideration.
      Other models of an expanding plume require eruptions from discrete sources, as
      well as less voluminous eruptions from a more extended source, to match the
      observations. No physical mechanism that matches the observations has been
      identified to control these eruptions. Here we report a mechanism in which
      temporal variations in tidal stress open and close the tiger-stripe rifts,
      governing the timing of eruptions. During each orbit, every portion of each tiger
      stripe rift spends about half the time in tension, which allows the rift to open,
      exposing volatiles, and allowing eruptions. In a complementary process, periodic
      shear stress along the rifts also generates heat along their lengths, which has
      the capacity to enhance eruptions. Plume activity is expected to vary
      periodically, affecting the injection of material into Saturn's E ring and its
      formation, evolution and structure. Moreover, the stresses controlling eruptions
      imply that Enceladus' icy shell behaves as a thin elastic layer, perhaps only a
      few tens of kilometres thick.

PMID- 17507978
TI  - Electronic measurement and control of spin transport in silicon.
AB  - The spin lifetime and diffusion length of electrons are transport parameters that
      define the scale of coherence in spintronic devices and circuits. As these
      parameters are many orders of magnitude larger in semiconductors than in metals,
      semiconductors could be the most suitable for spintronics. So far, spin transport
      has only been measured in direct-bandgap semiconductors or in combination with
      magnetic semiconductors, excluding a wide range of non-magnetic semiconductors
      with indirect bandgaps. Most notable in this group is silicon, Si, which (in
      addition to its market entrenchment in electronics) has long been predicted a
      superior semiconductor for spintronics with enhanced lifetime and transport
      length due to low spin-orbit scattering and lattice inversion symmetry. Despite
      this promise, a demonstration of coherent spin transport in Si has remained
      elusive, because most experiments focused on magnetoresistive devices; these
      methods fail because of a fundamental impedance mismatch between ferromagnetic
      metal and semiconductor, and measurements are obscured by other magnetoelectronic
      effects. Here we demonstrate conduction-band spin transport across 10 mum undoped
      Si in a device that operates by spin-dependent ballistic hot-electron filtering
      through ferromagnetic thin films for both spin injection and spin detection. As
      it is not based on magnetoresistance, the hot-electron spin injection and spin
      detection avoids impedance mismatch issues and prevents interference from
      parasitic effects. The clean collector current shows independent magnetic and
      electrical control of spin precession, and thus confirms spin coherent drift in
      the conduction band of silicon.

PMID- 17507979
TI  - Annealing-induced interfacial toughening using a molecular nanolayer.
AB  - Self-assembled molecular nanolayers (MNLs) composed of short organic chains and
      terminated with desired functional groups are attractive for modifying surface
      properties for a variety of applications. For example, organosilane MNLs are used
      as lubricants, in nanolithography, for corrosion protection and in the
      crystallization of biominerals. Recent work has explored uses of MNLs at thin
      film interfaces, both as active components in molecular devices, and as passive
      layers, inhibiting interfacial diffusion, promoting adhesion and toughening
      brittle nanoporous structures. The relatively low stability of MNLs on surfaces
      at temperatures above 350-400 degrees C (refs 12, 13), as a result of desorption
      or degradation, limits the use of surface MNLs in high-temperature applications.
      Here we harness MNLs at thin-film interfaces at temperatures higher than the MNL
      desorption temperature to fortify copper-dielectric interfaces relevant to wiring
      in micro- and nano-electronic devices. Annealing Cu/MNL/SiO2 structures at 400
      700 degrees C results in interfaces that are five times tougher than pristine
      Cu/SiO2 structures, yielding values exceeding approximately 20 J m(-2).
      Previously, similarly high toughness values have only been obtained using
      micrometre-thick interfacial layers. Electron spectroscopy of fracture surfaces
      and density functional theory modelling of molecular stretching and fracture show
      that toughening arises from thermally activated interfacial siloxane bridging
      that enables the MNL to be strongly linked to both the adjacent layers at the
      interface, and suppresses MNL desorption. We anticipate that our findings will
      open up opportunities for molecular-level tailoring of a variety of interfacial
      properties, at processing temperatures higher than previously envisaged, for
      applications where microlayers are not a viable option-such as in nanodevices or
      in thermally resistant molecular-inorganic hybrid devices.

PMID- 17507980
TI  - Survival times of anomalous melt inclusions from element diffusion in olivine and
      chromite.
AB  - The chemical composition of basaltic magma erupted at the Earth's surface is the
      end product of a complex series of processes, beginning with partial melting and
      melt extraction from a mantle source and ending with fractional crystallization
      and crustal assimilation at lower pressures. It has been proposed that studying
      inclusions of melt trapped in early crystallizing phenocrysts such as Mg-rich
      olivine and chromite may help petrologists to see beyond the later-stage
      processes and back to the origin of the partial melts in the mantle. Melt
      inclusion suites often span a much greater compositional range than associated
      erupted lavas, and a significant minority of inclusions carry distinct
      compositions that have been claimed to sample melts from earlier stages of melt
      production, preserving separate contributions from mantle heterogeneities. This
      hypothesis is underpinned by the assumption that melt inclusions, once trapped,
      remain chemically isolated from the external magma for all elements except those
      that are compatible in the host minerals. Here we show that the fluxes of rare
      earth elements through olivine and chromite by lattice diffusion are sufficiently
      rapid at magmatic temperatures to re-equilibrate completely the rare-earth
      element patterns of trapped melt inclusions in times that are short compared to
      those estimated for the production and ascent of mantle-derived magma or for
      magma residence in the crust. Phenocryst-hosted melt inclusions with anomalous
      trace-element signatures must therefore form shortly before magma eruption and
      cooling. We conclude that the assumption of chemical isolation of incompatible
      elements in olivine- and chromite-hosted melt inclusions is not valid, and we
      call for re-evaluation of the popular interpretation that anomalous melt
      inclusions represent preserved samples of unmodified mantle melts.

PMID- 17507981
TI  - First insights into the biodiversity and biogeography of the Southern Ocean deep
      sea.
AB  - Shallow marine benthic communities around Antarctica show high levels of
      endemism, gigantism, slow growth, longevity and late maturity, as well as
      adaptive radiations that have generated considerable biodiversity in some taxa.
      The deeper parts of the Southern Ocean exhibit some unique environmental
      features, including a very deep continental shelf and a weakly stratified water
      column, and are the source for much of the deep water in the world ocean. These
      features suggest that deep-sea faunas around the Antarctic may be related both to
      adjacent shelf communities and to those in other oceans. Unlike shallow-water
      Antarctic benthic communities, however, little is known about life in this vast
      deep-sea region. Here, we report new data from recent sampling expeditions in the
      deep Weddell Sea and adjacent areas (748-6,348 m water depth) that reveal high
      levels of new biodiversity; for example, 674 isopods species, of which 585 were
      new to science. Bathymetric and biogeographic trends varied between taxa. In
      groups such as the isopods and polychaetes, slope assemblages included species
      that have invaded from the shelf. In other taxa, the shelf and slope assemblages
      were more distinct. Abyssal faunas tended to have stronger links to other oceans,
      particularly the Atlantic, but mainly in taxa with good dispersal capabilities,
      such as the Foraminifera. The isopods, ostracods and nematodes, which are poor
      dispersers, include many species currently known only from the Southern Ocean.
      Our findings challenge suggestions that deep-sea diversity is depressed in the
      Southern Ocean and provide a basis for exploring the evolutionary significance of
      the varied biogeographic patterns observed in this remote environment.

PMID- 17507982
TI  - Wnt-dependent de novo hair follicle regeneration in adult mouse skin after
      wounding.
AB  - The mammalian hair follicle is a complex 'mini-organ' thought to form only during
      development; loss of an adult follicle is considered permanent. However, the
      possibility that hair follicles develop de novo following wounding was raised in
      studies on rabbits, mice and even humans fifty years ago. Subsequently, these
      observations were generally discounted because definitive evidence for follicular
      neogenesis was not presented. Here we show that, after wounding, hair follicles
      form de novo in genetically normal adult mice. The regenerated hair follicles
      establish a stem cell population, express known molecular markers of follicle
      differentiation, produce a hair shaft and progress through all stages of the hair
      follicle cycle. Lineage analysis demonstrated that the nascent follicles arise
      from epithelial cells outside of the hair follicle stem cell niche, suggesting
      that epidermal cells in the wound assume a hair follicle stem cell phenotype.
      Inhibition of Wnt signalling after re-epithelialization completely abrogates this
      wounding-induced folliculogenesis, whereas overexpression of Wnt ligand in the
      epidermis increases the number of regenerated hair follicles. These remarkable
      regenerative capabilities of the adult support the notion that wounding induces
      an embryonic phenotype in skin, and that this provides a window for manipulation
      of hair follicle neogenesis by Wnt proteins. These findings suggest treatments
      for wounds, hair loss and other degenerative skin disorders.

PMID- 17507983
TI  - Herpesvirus latency confers symbiotic protection from bacterial infection.
AB  - All humans become infected with multiple herpesviruses during childhood. After
      clearance of acute infection, herpesviruses enter a dormant state known as
      latency. Latency persists for the life of the host and is presumed to be
      parasitic, as it leaves the individual at risk for subsequent viral reactivation
      and disease. Here we show that herpesvirus latency also confers a surprising
      benefit to the host. Mice latently infected with either murine gammaherpesvirus
      68 or murine cytomegalovirus, which are genetically highly similar to the human
      pathogens Epstein-Barr virus and human cytomegalovirus, respectively, are
      resistant to infection with the bacterial pathogens Listeria monocytogenes and
      Yersinia pestis. Latency-induced protection is not antigen specific but involves
      prolonged production of the antiviral cytokine interferon-gamma and systemic
      activation of macrophages. Latency thereby upregulates the basal activation state
      of innate immunity against subsequent infections. We speculate that herpesvirus
      latency may also sculpt the immune response to self and environmental antigens
      through establishment of a polarized cytokine environment. Thus, whereas the
      immune evasion capabilities and lifelong persistence of herpesviruses are
      commonly viewed as solely pathogenic, our data suggest that latency is a
      symbiotic relationship with immune benefits for the host.

PMID- 17507984
TI  - Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell
      polarity.
AB  - Helicobacter pylori cagA-positive strains are associated with gastritis,
      ulcerations and gastric adenocarcinoma. CagA is delivered into gastric epithelial
      cells and, on tyrosine phosphorylation, specifically binds and activates the SHP2
      oncoprotein, thereby inducing the formation of an elongated cell shape known as
      the 'hummingbird' phenotype. In polarized epithelial cells, CagA also disrupts
      the tight junction and causes loss of apical-basolateral polarity. We show here
      that H. pylori CagA specifically interacts with PAR1/MARK kinase, which has an
      essential role in epithelial cell polarity. Association of CagA inhibits PAR1
      kinase activity and prevents atypical protein kinase C (aPKC)-mediated PAR1
      phosphorylation, which dissociates PAR1 from the membrane, collectively causing
      junctional and polarity defects. Because of the multimeric nature of PAR1 (ref.
      14), PAR1 also promotes CagA multimerization, which stabilizes the CagA-SHP2
      interaction. Furthermore, induction of the hummingbird phenotype by CagA
      activated SHP2 requires simultaneous inhibition of PAR1 kinase activity by CagA.
      Thus, the CagA-PAR1 interaction not only elicits the junctional and polarity
      defects but also promotes the morphogenetic activity of CagA. Our findings
      revealed that PAR1 is a key target of H. pylori CagA in the disorganization of
      gastric epithelial architecture underlying mucosal damage, inflammation and
      carcinogenesis.

PMID- 17507985
TI  - Structural basis for cofactor-independent dioxygenation in vancomycin
      biosynthesis.
AB  - Enzyme-catalysed oxidations are some of the most common transformations in
      primary and secondary metabolism. The vancomycin biosynthetic enzyme DpgC belongs
      to a small class of oxygenation enzymes that are not dependent on an accessory
      cofactor or metal ion. The detailed mechanism of cofactor-independent oxygenases
      has not been established. Here we report the first structure of an enzyme of this
      oxygenase class in complex with a bound substrate mimic. The use of a designed,
      synthetic substrate analogue allows unique insights into the chemistry of oxygen
      activation. The structure confirms the absence of cofactors, and electron density
      consistent with molecular oxygen is present adjacent to the site of oxidation on
      the substrate. Molecular oxygen is bound in a small hydrophobic pocket and the
      substrate provides the reducing power to activate oxygen for downstream chemical
      steps. Our results resolve the unique and complex chemistry of DpgC, a key enzyme
      in the biosynthetic pathway of an important class of antibiotics. Furthermore,
      mechanistic parallels exist between DpgC and cofactor-dependent flavoenzymes,
      providing information regarding the general mechanism of enzymatic oxygen
      activation.

PMID- 17507990
TI  - SYT-SSX fusion is absent in sarcomatoid mesothelioma allowing its distinction
      from synovial sarcoma of the pleura.
AB  - The diagnosis of sarcomatoid mesothelioma is still a worldwide challenge and it
      is often difficult, both clinically and by morphological analysis, to
      differentiate sarcomatoid mesothelioma from synovial sarcoma, the most frequent
      intrathoracic sarcoma. To confirm the absence of the synovial sarcoma
      translocation t(X; 18) (SYT-SSX) in sarcomatoid mesothelioma, and to test its
      usefulness differentiating sarcomatoid mesothelioma from synovial sarcoma, 28
      tumours were examined using the reverse transcriptase-polymerase chain reaction.
      RNA was extracted from paraffin blocks using standard methods, reverse
      transcribed and PCR performed. Molecular analysis completed in two independent
      laboratories showed that sarcomatoid mesothelioma samples were negative for the
      t(X-18). This result confirms the usefulness of this analysis in differentiating
      sarcomatoid mesothelioma from synovial sarcoma.

PMID- 17507989
TI  - Achaete-scute homolog-1 linked to remodeling and preneoplasia of pulmonary
      epithelium.
AB  - The basic helix-loop-helix protein achaete-scute homolog-1 (ASH1) is involved in
      lung neuroendocrine (NE) differentiation and tumor promotion in SV40 transgenic
      mice. Constitutive expression of human ASH-1 (hASH1) in mouse lung results in
      hyperplasia and remodeling that mimics bronchiolization of alveoli (BOA), a
      potentially premalignant lesion of human lung carcinomas. We now show that this
      is due to sustained cellular proliferation in terminal bronchioles and resistance
      to apoptosis. Throughout the airway epithelium the expression of anti-apoptotic
      Bcl-2 and c-Myb was increased and Akt/mTOR pathway activated. Moreover, the
      expression of matrix metalloproteases (MMPs) including MMP7 was specifically
      enhanced at the bronchiolo-alveolar duct junction and BOA suggesting that MMPs
      play a key role in this microenvironment during remodeling. We also detected MMP7
      in 70% of human BOA lesions. Knockdown of hASH1 gene in human lung cancer cells
      in vitro suppressed growth by increasing apoptosis. We also show that forced
      expression of hASH1 in immortalized human bronchial epithelial cells decreases
      apoptosis. We conclude that the impact of hASH1 is not limited to cells with NE
      phenotype. Rather, constitutive expression of hASH1 in lung epithelium promotes
      remodeling through multiple pathways that are commonly activated during lung
      carcinogenesis. The collective results suggest a novel model of BOA formation via
      hASH1-induced suppression of the apoptotic pathway. Our study yields a promising
      new preclinical tool for chemoprevention of peripheral lung carcinomas.

PMID- 17507991
TI  - High-level JAG1 mRNA and protein predict poor outcome in breast cancer.
AB  - Notch receptors regulate cell fate determination, stem cell self-renewal,
      proliferation and apoptosis. We previously reported that elevated mRNA expression
      of the Notch ligand JAG1 identifies breast cancer patients with a poor prognosis.
      Here we show through immunohistochemical analysis of the same breast cancer cases
      (N=127) that patients with tumors expressing high levels of JAG1 protein had a
      worse outcome than those with tumors expressing low levels (10-year survival 26
      vs 48%, and median survival 63 vs 108 months, respectively; P=0.03). We also
      describe the novel application of the Allred score to quantify JAG1 mRNA and
      protein expression levels. Using the Allred score, patients with tumors
      expressing high levels of JAG1 mRNA had a worse outcome than those with tumors
      expressing low levels (10-year survival 16 vs 47%, and median survival 43 months
      vs 100 months, respectively; P<0.001). Interestingly, when tumors were classified
      as either high or low for JAG1 mRNA or protein expression, there was only 65%
      agreement (kappa=0.08) between the two methods of expression analysis. When JAG1
      mRNA and protein data were combined, patients with tumors expressing low levels
      of both had a 10-year survival of 53% and median survival of 131 months. In
      comparison, patients with tumors expressing either high levels of JAG1 protein,
      mRNA or both had reduced 10-year survival and median survival (31%, 19%, 11% and
      77, 43, 23 months respectively; P<0.0001). There was marginal evidence of an
      interaction effect (P=0.055), which indicated that the prognostic value of JAG1
      protein was limited to the JAG1 mRNA-low subgroup. These data show that the
      Allred score can be used to rapidly quantify JAG1 mRNA and protein levels in
      breast cancer to identify patients who have a significant survival disadvantage
      and who may benefit from therapies (such as gamma-secretase inhibitors) that
      target signaling through the Notch pathway.

PMID- 17507992
TI  - Retraction. Single-walled carbon nanotubes-mediated in vivo and in vitro delivery
      of siRNA into antigen-presenting cells.

PMID- 17507997
TI  - The quantitative JAK2 V617F neutrophil allele burden does not correlate with
      thrombotic risk in essential thrombocytosis.

PMID- 17507998
TI  - Demonstration of MPLW515K, but not JAK2V617F, in in vitro expanded CD4+ T
      lymphocytes.

PMID- 17507999
TI  - Low IPSS score and bone marrow hypocellularity in MDS patients predict
      hematological responses to antithymocyte globulin.
AB  - Immunosuppressive therapy has been shown to induce sustained hematological
      responses in a subset of patients with myelodysplastic syndromes (MDS). In
      particular, antithymocyte globulin (ATG), a polyclonal immunoglobulin induces
      hematological responses in up to 60% of MDS patients. We report herein on the
      results of a retrospective multicenter study on the use of ATG in the treatment
      of 96 patients with MDS. Patients were evaluated for duration of response to ATG,
      as well as survival after administration of ATG. The median age of the cohort was
      54.7 years (range: 19-75 years), with a median follow-up of 33.8 months (range:
      0.8-133 months). A total of 40 patients (42%) achieved a hematological response,
      of which 30 patients (75%) had a durable hematological response lasting a median
      duration of 31.5 months (range: 6-92 months). On multivariate analysis, both low
      International Prognostic Scoring System (IPSS) and bone marrow (BM)
      hypocellularity were independent predictive factors for improved response to ATG
      (IPSS Int-2/high: odds ratio (OR) 0.08, P=0.018 and BM normo/hypercellularity: OR
      0.49, P=0.012). In addition, IPSS was the sole predictor of overall survival,
      with Int-2/high risk patients having a significantly poorer survival outcome (OR
      0.08, P<0.01). In conclusion, this study identifies BM hypocellularity and a low
      IPSS as important factors predicting response to ATG.

PMID- 17508000
TI  - Synergistic effect of AS101 and Bryostatin-1 on myeloid leukemia cell
      differentiation in vitro and in an animal model.
AB  - We evaluated the synergistic activity of AS101 (ammonium trichloro-(dioxoethylene
      0-0')-tellurate) with the protein kinase C (PKC) activators, Bryostatin-1 and
      phorbol-12-myristate-13-acetate (PMA), on human myelocytic leukemia cell
      differentiation in vitro, and in a mouse model. Use of AS101 with Bryostatin-1 or
      with a low concentration of PMA resulted in the differentiation of HL-60 cell
      line to cells with characteristics of macrophages. A similar synergistic effect
      was found in vivo. Compared with mice treated with AS101 alone or with Bryostatin
      1 alone, the infiltration of leukemic cells into the spleen and the peritoneum of
      mice treated with both compounds, as well as the number of the HL-60 colonies
      extracted from those organs, were markedly reduced. The antitumor effects were
      associated with significantly prolonged survival (100% for 125 days) of the
      treated mice. Finally, the mechanism of action of this antitumor effect was
      explored, and was found to involve the Ras/extracellular signal-regulated kinase
      signaling pathway. Combined treatment with AS101 and Bryostatin-1 synergistically
      increased p21(waf1) expression levels independently of p53. Upregulation of
      p21(waf1) was necessary for HL-60 cell differentiation, which was found to be
      both c-raf-1 and mitogen-activated protein kinase dependent. This study may have
      implications for the development of strategies to induce differentiation in
      myeloid leukemias, myelodysplasias and possibly in other malignancies.

PMID- 17508001
TI  - HS1 complexes with cytoskeleton adapters in normal and malignant chronic
      lymphocytic leukemia B cells.

PMID- 17508002
TI  - Viewpoint: What is the role of allogeneic haematopoietic cell transplantation in
      the era of reduced-intensity conditioning--is there still an upper age limit? A
      focus on myeloid neoplasia.
AB  - Allogeneic haematopoietic cell transplantation (HCT) is the most effective
      curative therapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes
      (MDS). Incidence of AML and MDS increases with age, peaking in the seventh
      decade. Despite improved Ara-C and anthracyclin-based chemotherapy regimens, the
      prognosis of AML in patients beyond 60 years of age is dismal. The introduction
      of peripheral blood-derived stem cell grafts into allogeneic HCT and the known
      anti-leukaemic effect of donor lymphocyte infusions paved the way for reduced
      intensity conditioning (RIC) allogeneic stem-cell transplantation, which makes
      transplant in advanced age possible and significantly reduces transplant-related
      organ toxicity and mortality. The success of RIC HCT relies on the alloreactivity
      of the donor immune system and the graft-versus-leukaemia effect. We try to
      answer the following questions in this paper: who should receive RIC HCT? when
      and how should the transplant be performed? is there an upper age limit and what
      is the future of RIC HCT?

PMID- 17508003
TI  - History of infections and vaccinations and risk of lymphoid neoplasms: does
      influenza immunization reduce the risk?

PMID- 17508004
TI  - A novel ETV6-PDGFRB fusion transcript missed by standard screening in a patient
      with an imatinib responsive chronic myeloproliferative disease.

PMID- 17508005
TI  - CTLA-4 blockade in murine bone marrow chimeras induces a host-derived
      antileukemic effect without graft-versus-host disease.
AB  - We studied the effect of CTLA-4 blockade on graft-versus-leukemia and graft
      versus-host responses in a mouse model of minor histocompatibility-mismatched
      bone marrow transplantation. Early CTLA-4 blockade induced acute graft-versus
      host disease. Delayed CTLA-4 blockade resulted in a lethal condition with
      lymphosplenomegaly, but with stable mixed T-cell chimerism, unchanged
      alloreactive T-cell frequencies and absent anti-host reactivity in vitro. In
      contrast, multiorgan lymphoproliferative disease with autoimmune hepatitis and
      circulating anti-DNA auto-antibodies were documented. Splenic lymphocytes
      exhibited ex vivo spontaneous proliferation and a marked proliferative response
      against host-type dendritic cells pulsed with syngeneic (host-type) tissue
      peptides. Both phenomena were exclusively mediated by host and not donor T cells,
      supporting an autoimmune pathogenesis. Selectively host-derived T-cell immune
      reactivity was equally documented against leukemia-peptide-pulsed dendritic
      cells, and this was paralleled by a strong in vivo antileukemic effect in anti
      CTLA-4-treated and subsequently leukemia-challenged chimeras. In conclusion,
      delayed CTLA-4 blockade induced a host-derived antileukemic effect, occurring in
      the context of an autoimmune syndrome and strictly separated from graft-versus
      host disease. Both antileukemic and autoimmune responses depended on the
      allogeneic component, as neither effect was seen after syngeneic bone marrow
      transplantation. Our findings reveal the potential of using CTLA-4 blockade to
      establish antileukemic effects after allogeneic hematopoietic stem cell
      transplantation, provided autoimmunity can be controlled.

PMID- 17508006
TI  - WT1 transcript amount discriminates secondary or reactive eosinophilia from
      idiopathic hypereosinophilic syndrome or chronic eosinophilic leukemia.
AB  - Idiopathic hypereosinophilic syndromes (HES) comprise a spectrum of indolent to
      aggressive diseases characterized by persistent hypereosinophilia.
      Hypereosinophilia can result from the presence of a defect in the hematopoietic
      stem cell giving rise to eosinophilia, it can be present in many
      myeloproliferative disorders or alternatively it may be a reactive form,
      secondary to many clinical conditions. The hybrid gene FIP1L1-PDGRFalpha was
      identified in a subset of patients presenting with HES or chronic eosinophilic
      leukemia (CEL). In spite of this, the majority of HES patients do not present
      detectable molecular lesions and for many of them the diagnosis is based on
      exclusion criteria and sometimes it remains doubt. In this study we explored the
      possibility to distinguish between HES/CEL and reactive hypereosinophilia based
      on WT1 transcript amount. For this purpose, 312 patients with hypereosinophilia
      were characterized at the molecular and cytogenetic level and analyzed for WT1
      expression at diagnosis and during follow-up. This study clearly demonstrates
      that WT1 quantitative assessment allows to discriminate between HES/CEL and
      reactive eosinophilia and represents a useful tool for disease monitoring
      especially in the patients lacking a marker of clonality.

PMID- 17508007
TI  - Restricted tissue tropism and acquired resistance to Sindbis viral vector
      expression in the absence of innate and adaptive immunity.
AB  - Our previous studies suggest that replication-defective Sindbis vectors might be
      promising agents for specific tumor targeting and detection. However, the effects
      of innate and/or adaptive anti-viral immunity, in particular, the IFN-I/STAT1
      signaling pathway, may impact their therapeutic potential. Using a bioluminescent
      imaging system, we demonstrate that although most normal cells are not
      permissively transduced by replication-defective Sindbis vector, transduction of
      liver non-sinusoidal endothelial occurs the first time IFN-I/STAT1 signaling
      deficient mice are inoculated with the vector. Transduction of some cells is not
      surprising since STAT1 knockout animals show significant delay in IFN responses
      such as the production of IFN-alpha/beta and transcriptional activation of
      several anti-viral genes (IRF7, RIG-I, PKR, TLR3, USP18, ISG15). However, beyond
      the initial vector transduction, which resolves rapidly, secondary inoculums of
      Sindbis vectors do not transduce any liver cells, suggesting that an alternative
      antiviral pathway may protect against further transduction. Other known signaling
      pathways were examined using mice lacking functional TLR3, tumor necrosis
      factoralphaR or nuclear factor-kappa B (p50). Surprisingly, none of those
      pathways seem to play a significant role in anti-Sindbis responses. Thus it
      appears that in vivo, in contrast to the ready transduction of tumor cells,
      transduction of normal cells by replication-defective Sindbis vector is limited,
      possibly by a novel mechanism.

PMID- 17508008
TI  - Fiber-modified adenovirus vectors containing the TAT peptide derived from HIV-1
      in the fiber knob have efficient gene transfer activity.
AB  - The interaction between viral capsid proteins and specific molecules exposed on
      the plasma membrane of the cells is involved in the viral tropism. A human
      adenovirus (Ad) belonging to subgroups A, C, D, E and F infects cells via the
      interaction between the fiber knob and the primary receptor, the coxsackievirus
      and adenovirus receptor (CAR). Conventional human adenovirus type 5 (hAd5)
      vectors show efficient transduction in CAR-positive cells; in contrast, hAd5
      vector application is limited by poor transduction into cells lacking CAR
      expression. In the present study, to broaden the tropism of hAd5 vectors, we
      generated hAd5 vectors containing the TAT peptide, which is a protein
      transduction domain derived from human immunodeficiency virus, in the HI loop of
      the fiber knob (Ad-TAT(HI)-L2) or the C-terminus of the fiber knob (Ad-TAT(C)
      L2). In CAR-negative adherent cells, Ad-TAT(HI)-L2 and Ad-TAT(C)-L2 showed
      approximately 50- to 500-fold higher gene expression than the conventional hAd5
      vector (Ad-L2). Ad-TAT(HI)-L2 was also more efficient than Ad-L2 in blood cell
      lines and in two types of primary cultured human vascular smooth muscle cells,
      which are almost refractory to Ad-L2. Furthermore, Ad-TAT(HI)-L2 was more
      efficient than other types of fiber-modified Ad vectors, which harbor an RGD (Arg
      Gly-Asp) or a poly-lysine (KKKKKKK;K7) peptide in the HI loop or the C-terminus
      of the fiber knob, respectively. Ad-TAT(HI)-L2 efficiently transduced the organs
      in levels and patterns that were roughly similar to those of Ad-L2 after being
      systemically injected into mice. To the best of our knowledge, this study is the
      first report showing that hAd5 vectors containing the TAT peptide in the fiber
      knob could efficiently transduce cells independently of CAR. These Ad vectors
      should be useful for gene functional analysis and gene therapy.

PMID- 17508009
TI  - Human neural stem cells target and deliver therapeutic gene to experimental
      leptomeningeal medulloblastoma.
AB  - Medulloblastomas are highly malignant neuroectodermal cerebellar tumors of
      children. One of the reasons for the difficulty for the treatment of
      medulloblastomas is their inherent tendency to metastasize through the
      cerebrospinal fluid (CSF) pathway leading to leptomeningeal dissemination.
      Recently, genetically modified neural stem cells (NSCs) were shown to have the
      capability of selectively migrating into glioma mass and delivering therapeutic
      agents with significant therapeutic benefits. In the present study, we applied
      the NSC strategy to target medulloblastomas, particularly their leptomeningeal
      dissemination. We used NSCs that were retrovirally transduced with the cytosine
      deaminase gene (CD-NSCs). In vitro studies demonstrated that CD-NSCs had
      sufficient migratory activity toward medulloblastoma cells and exerted a
      remarkable bystander effect on these cells following the application of 5
      fluorocytosine (5-FC). It is noteworthy that neutralization of the hepatocyte
      growth factor blocked their migration In animal studies using our leptomeningeal
      dissemination model, CD-NSCs implanted directly into CSF space were shown to
      distribute diffusely within the disseminated tumor cells and could provide
      remarkable antitumor effect after intraperitoneal administration of 5-FC.
      Furthermore, CD-NSC treatment followed by 5-FC administration prolonged survival
      periods significantly in experimental animals. Our data suggest that the CD-NSC
      strategy can also be applied to target leptomeningeal dissemination of
      medulloblastomas.

PMID- 17508010
TI  - Key to prevention.

PMID- 17508011
TI  - Plasma levels of fibrinogen and C-reactive protein are related to interleukin-6
      gene -572C>G polymorphism in subjects with and without hypertension.
AB  - Hypertension is an important risk factor for cardiovascular diseases. There is
      increasing evidence suggesting that inflammation is involved in the development
      of hypertension. Interleukin-6 (IL-6) is an important mediator of inflammatory
      response and the major regulator of hepatic production of acute phase proteins,
      such as fibrinogen and C-reactive protein (CRP), which have been associated with
      hypertension and cardiovascular diseases. Therefore, we studied the association
      of single nucleotide polymorphism (SNP) in the IL-6 gene (IL6) promoter with
      plasma levels of fibrinogen, CRP and hypertension. Five hundred and two Hong Kong
      Chinese subjects (282 normotensives and 220 hypertensives) were recruited. IL-6
      gene promoter was examined for polymorphism and the study subjects were genotyped
      for any SNP identified. The IL6 -572C>G polymorphism (rs1800796) was found with a
      frequency of 0.23 for the minor G allele. Subjects with the -572G allele had
      significantly higher plasma fibrinogen (3.06+/-0.57 vs 2.83+/-0.60, P=0.002) and
      CRP (interquartile range 0.33-1.56 vs 0.12-0.93, P=0.003) levels than those
      without. The -572C>G polymorphism was found to be an independent predictor of
      fibrinogen and CRP levels after adjusting for confounding factors. Plasma
      concentrations of fibrinogen and CRP correlated with systolic blood pressure.
      However, the -572C/G genotype frequencies did not differ between hypertensive and
      normotensive subjects, and there was no association between -572C>G polymorphism
      and blood pressure. Our results provide evidence that there is a clear genetic
      influence of IL6 -572C>G polymorphism on plasma levels of fibrinogen and CRP, but
      this polymorphism does not lead to elevated blood pressure.

PMID- 17508012
TI  - Metabolic syndrome and left ventricular hypertrophy in a general population.
      Results from the Gubbio Study.
AB  - Aims of this study were to investigate the prevalence of metabolic syndrome (MS),
      diagnosed according to the International Diabetes Federation (IDF) criteria and
      its relationship with echocardiographic parameters of cardiac structure and
      function. The study was performed in 707 subjects, age 45-54 years, of the Gubbio
      Population Study who underwent a comprehensive examination including measurement
      of body size, blood pressure (BP) and heart rate, 12-lead electrocardiogram,
      Doppler echocardiography, standardized blood and urine laboratory tests. One
      hundred and fifty-three subjects were found to have MS, which was more frequent
      among hypertensive patients than normotensive controls (36.2 vs 13.7%, P<0.001).
      Apart from visceral obesity present in all subjects by definition according to
      the IDF criteria, high levels of BP (>130/85 mm Hg) and triglycerides (>or=150
      mg/dl) were the most frequently observed components of the syndrome, since their
      prevalence averaged 75% of those with the syndrome. Left ventricular mass (95.6+/
      22 vs 86.4+/-22 g/m(2); P<0.001) and prevalence of left ventricular hypertrophy
      were increased in the subgroup with MS. Waist circumference, BP and blood glucose
      were the components of the syndrome with stronger impact on cardiac mass. An
      early impairment of the diastolic function was detected in this subgroup with a
      reduction of the early-to-late diastolic filling (0.91+/-0.17 vs 0.99+/-0.23,
      P<0.001). The results of the present study indicate that MS is frequent in middle
      aged general population, particularly in subjects with arterial hypertension. The
      syndrome is associated to the increase in ventricular mass and the early
      impairment of diastolic function.

PMID- 17508013
TI  - Endothelium-dependent relaxation is resistant to inhibition of nitric oxide
      synthesis, but sensitive to blockade of calcium-activated potassium channels in
      essential hypertension.
AB  - In human essential hypertension (EH), endothelium-dependent relaxation can occur
      independent of nitric oxide (NO) and prostacyclin (PGI(2)). Recent in vivo data
      suggest that rapid compensatory upregulation of endothelial cytochrome P450
      epoxygenase 2C9 occurs to preserve vasorelaxation under conditions of decreased
      NO bioavailability. As one of the vascular actions of CYP2C9 is to modulate small
      and intermediate conductance endothelial calcium-activated potassium channels
      (SK(Ca) and IK(Ca)), we examined whether endothelium-dependent relaxation is
      sensitive to inhibitors of these channels (apamin and charybdotoxin) in
      resistance-sized vessels from human with EH. Subcutaneous gluteal biopsies were
      performed on 12 humans with EH and 12 matched control subjects. Resistance
      arteries were dissected and relaxation responses to carbachol were assessed ex
      vivo using wire myography in the presence of: (i) N(G)-nitro-L-arginine (L
      NOARG)/indomethacin; and (ii) apamin/charybdotoxin. Maximal carbachol relaxation
      was impaired in EH vs control subjects. No differences in responses were observed
      with the endothelium-independent agonist, S-nitroso-N-acetyl-penicillamine.
      Relaxation to carbachol was attenuated following incubation with L
      NOARG/indomethacin in vessels from control subjects (P<0.01 analysis of variance
      (ANOVA)), but not in vessels from patients with EH. The reverse pattern was seen
      following apamin/charybdotoxin with carbachol relaxation attenuated only in EH
      vessels (P<0.001 ANOVA). Endothelium-dependent relaxation is resistant to
      endothelial nitric oxide synthase inhibition but sensitive to blockade of calcium
      activated potassium channels in human EH. Studies with more specific inhibitors
      are required to determine whether this response is mediated by endothelial
      potassium channel subtypes (SK(Ca) and IK(Ca)).

PMID- 17508014
TI  - Determinants of aortic input impedance in two ethnic populations: impact of
      obesity.

PMID- 17508015
TI  - Persistence and adherence with antihypertensive drug therapy in a German sickness
      fund population.

PMID- 17508016
TI  - Peripheral artery disease and hypertension: the relation between ankle-brachial
      index and mortality.

PMID- 17508017
TI  - Clinical evidence epistemology.

PMID- 17508018
TI  - Novel ABCA12 mutations identified in two cases of non-bullous congenital
      ichthyosiform erythroderma associated with multiple skin malignant neoplasia.

PMID- 17508019
TI  - Human basal cell carcinoma is associated with Foxp3+ T cells in a Th2 dominant
      microenvironment.
AB  - Basal cell carcinoma (BCC), the most common human cancer, undergoes spontaneous
      regression in certain circumstances, which is potentially immune-mediated. To
      understand the immune response surrounding BCCs, we characterized the genomic,
      protein, and cellular microenvironment associated with BCC in comparison to
      normal skin. Our results demonstrated the following: (1) CD4+ CD25+ Foxp3+
      surround epithelial tumor aggregates; (2) Immature dendritic cells (DCs) were
      abundant in the tumor microenvironment; (3) BCC showed increased expression of IL
      4, IL-10, and CCL22 and increased expression of interferon-associated genes
      (IFI27, IRF1, IRF7, and G1P2) and IL-12/23, gene indicating a Th2 dominant
      microenvironment. Our findings suggest a dynamic state within the immune
      microenvironment associated with BCC. The finding of phenotypic T regs, in
      conjunction with immature DCs and Th2 cytokines, suggests an attenuated state of
      immunity to human BCC. In contrast, abundant CD8+ T cells, an interferon signal,
      and IL-12/23 suggest partial host antitumor response. A better understanding of
      these opposing forces within the immune microenvironment may facilitate
      development of more potent immune-based treatment for BCC and other human
      carcinomas.

PMID- 17508020
TI  - Androgen receptor co-activator Hic-5/ARA55 as a molecular regulator of androgen
      sensitivity in dermal papilla cells of human hair follicles.
AB  - Androgen site-specifically affects human hair growth after puberty through
      androgen receptors in the dermal papilla, which transactivate target genes acting
      in conjunction with co-activators. To examine the regulation of androgen
      sensitivity in hair follicles, we focused on androgen receptor co-activator Hic
      5/ARA55. Its interaction with transfected androgen receptor in beard dermal
      papilla cells was confirmed with mammalian two-hybrid assays. The
      semiquantitative reverse transcriptase-polymerase chain reaction showed that Hic
      5/ARA55 mRNA expression was high in dermal papilla cells from the beard and bald
      frontal scalp but low in cells from the occipital scalp. To determine whether Hic
      5/ARA55 mRNA level correlates with its endogenous activity, we studied the effect
      of dominant negative Hic-5/ARA55 on transfected androgen receptor transactivation
      induced by R1881 using mouse mammary tumor virus-luciferase assays. We found that
      it suppressed the transactivation by 64.5 and 71.4% in dermal papilla cells from
      the beard and bald frontal scalp, respectively, whereas it showed no significant
      effect in cells from the occipital scalp. Our findings suggest that Hic-5/ARA55
      is a molecular regulator for androgen sensitivity in human hair follicles.

PMID- 17508021
TI  - Langerhans cells and lymph node dendritic cells express the tight junction
      component claudin-1.
AB  - Claudin-1 is a critical structural component of tight junctions that have an
      important role in adhesive properties, barrier function, and paracellular
      transport of epithelia and other nonhematopoietic tissues. We found claudin-1 in
      murine CD207+ Langerhans cells (LC) residing in epidermis. Claudin-1 was not
      detected in other skin dendritic cells (DC). LC expressed claudin-1 in steady
      state and inflamed skin. Claudin-1 was demonstrated further in lymph node LC
      under steady state and inflammatory conditions, including after direct tracking
      with tetramethylrhodamine-isothiocyanate (TRITC). All subsets of skin draining
      lymph node DC defined by CD205, CD11b, CD11c, and CD8, including a presumably
      blood-borne lymph node resident CD8+CD207+ LC population, were claudin-1+. TRITC
      tracking demonstrated claudin-1 in CD207- skin migrant DC in the lymph node,
      suggesting upregulation of this molecule during migration or once arrived in the
      lymph node. Claudin-1 expression in CD207+ cells was confirmed at the protein and
      mRNA levels. Transforming growth factor-beta, a factor critical for the induction
      of LC in vitro and in vivo, stimulated the accumulation of claudin-1 mRNA and
      protein when added to bone marrow cells cultured with GM-CSF and IL-4. Claudin-1
      may thus have an important function in adhesion and/or migration of LC.

PMID- 17508022
TI  - MC1R expression in skin: is it confined to melanocytes?

PMID- 17508023
TI  - Transient receptor potential vanilloid-1 mediates heat-shock-induced matrix
      metalloproteinase-1 expression in human epidermal keratinocytes.
AB  - Transient receptor potential vanilloid-1 (TRPV1), a heat-gated channel, was
      recently found on human keratinocytes and the activation of epidermal TRPV1 was
      known to induce release of proinflammatory mediators. However, the functional
      consequences of TRPV1 activation in cutaneous physiology and pathology have not
      been elucidated clearly. In this study, we investigated the role of TRPV1 on the
      matrix metalloproteinase (MMP)-1 expression induced by heat shock in human
      epidermal keratinocytes. Heat shock induced the expression of MMP-1 mRNA and
      protein in a temperature-dependent manner in an immortalized human keratinocyte
      cell line (HaCaT) and normal human epidermal keratinocytes (NHK). Heat-shock
      induced MMP-1 expression was decreased by treatment of the TRPV1 inhibitors
      (capsazepine and ruthenium red) or knockdown of TRPV1 using RNA interference in
      HaCaT cells. Overexpression of TRPV1 greatly increased heat-shock-induced MMP-1
      promoter activity in HEK 293 cells. Furthermore, direct activation of TRPV1 by
      capsaicin, a TRPV1 agonist, increased MMP-1 expression. We found that heat shock
      induced calcium influx through TRPV1 and that extracellular calcium was necessary
      for heat-shock-induced MMP-1 expression in HaCaT cells. Taken together, our
      results suggest that heat-shock-induced MMP-1 expression is mediated by
      activation of TRPV1 and is dependent on a calcium-dependent signaling process in
      human epidermal keratinocytes.

PMID- 17508025
TI  - Folic acid: cellular uptake and penetration into human skin.

PMID- 17508024
TI  - Comparison of a treatment strategy combining CCI-779 plus DTIC versus DTIC
      monotreatment in human melanoma in SCID mice.
AB  - This study compares the antineoplastic potential of a novel treatment strategy
      combining cell cycle inhibitor-779 (CCI-779) plus dacarbazine (DTIC) versus DTIC
      monotreatment, the current chemotherapeutic mainstay in combating metastatic
      melanoma. A controlled four-group parallel study design comprising 24-40 mice per
      tumor cell line was used in a severe combined immunodeficiency (SCID)-mouse
      xenotransplantation model. SCID mice were injected with 518A2, Mel-JUSO, or 607B
      human melanoma cells. After they developed tumors, mice received daily CCI-779 or
      solvent over 14 days. From treatment day 4-8 mice were additionally injected with
      DTIC or saline. Treatment with CCI-779 plus DTIC was superior to single agent
      DTIC in two out of three cell lines (P<0.05). The tumor weight reduction was 44+/
      17 and 61+/-6% compared with DTIC monotreatment in Mel-JUSO and 607B melanomas,
      respectively (P<0.05). In contrast, in 518A2 xenotransplants, CCI-779 plus DTIC
      treatment was as effective as DTIC monotreatment. CCI-779 monotherapy exerted no
      statistically significant antitumor effect. Collectively, these data indicate
      that CCI-779 has the potential to increase the chemotherapeutic efficacy, as the
      combination of CCI-779 plus DTIC proved to be more efficacious compared to DTIC
      monotherapy in two out of three melanoma cell lines in vivo.

PMID- 17508026
TI  - ERK1/2 is highly phosphorylated in melanoma metastases and protects melanoma
      cells from cisplatin-mediated apoptosis.
AB  - Activation (phosphorylation) of mitogen-activated protein kinase (MAPK) signal
      transduction through BRAF and RAS causes a variety of functional effects
      including cell survival and cell death. In this study, we observed high
      extracellular signal-regulated kinase (ERK)1/2 phosphorylation levels in clinical
      melanoma metastases and various melanoma cell lines. Treatment of melanoma cell
      lines with cisplatin, a potent antitumor agent, increased the level of
      phosphorylated-ERK (P-ERK)1/2 and enhanced chemoresistance through activation of
      the cell survival protein 90-kDa ribosomal S6 kinase (RSK)1. The mitogen
      activated protein kinase kinase (MEK) inhibitor (U0126) was able to block this
      effect and reduced cell viability and sensitized cells to cisplatin-induced
      apoptosis, as shown by PARP cleavage, caspase 3 expression, and annexin-V
      staining. In conclusion, the MAP kinase-ERK pathway is activated in melanoma and
      reduces the sensitivity of melanoma to cisplatin. Thus, inhibition of ERK1/2 in
      combination with selected chemotherapeutic agents may hold promise for more
      effective therapy of melanoma.

PMID- 17508027
TI  - Changing venues for tumour suppression: balancing destruction and localization by
      monoubiquitylation.
AB  - Recent studies have shown that three major tumour-suppressor proteins undergo
      monoubiquitylation-mediated nuclear-cytoplasmic shuttling. Importantly, this
      mechanism has consequences for cancer and implies that proper localization is
      central to the function of tumour suppressors. This Progress article highlights
      recent efforts demonstrating that monoubiquitylation coupled to nuclear
      cytoplasmic shuttling might be a novel regulatory mechanism that directly
      influences the function of tumour suppressors.

PMID- 17508028
TI  - Snail, Zeb and bHLH factors in tumour progression: an alliance against the
      epithelial phenotype?
AB  - The molecular mechanisms that underlie tumour progression are still poorly
      understood, but recently our knowledge of particular aspects of some of these
      processes has increased. Specifically, the identification of Snail, ZEB and some
      basic helix-loop-helix (bHLH) factors as inducers of epithelial-mesenchymal
      transition (EMT) and potent repressors of E-cadherin expression has opened new
      avenues of research with potential clinical implications.

PMID- 17508030
TI  - Genomic variations within DEFB1 are associated with the susceptibility to and the
      fatal outcome of severe sepsis in Chinese Han population.
AB  - Sepsis is a systemic inflammatory response syndrome to infection. Human beta
      defensin 1 (DEFB1) is a multifunctional mediator in infection and inflammation,
      which has been largely explored in ex vivo studies. The present case-control
      study was designed to investigate whether DEFB1 genomic variations are associated
      with the susceptibility to and the outcome of severe sepsis in 211 patients with
      severe sepsis and 157 ethnic-matched healthy controls. After correcting for
      multiple testing, the -44G/C was the only polymorphism found to show significant
      associations with both the susceptibility to and the fatal outcome of severe
      sepsis (P=0.0049, odd ratio (OR) 1.971 and P=0.002, OR 2.406, respectively).
      Haplotype -20A/-44C/-52G showed a protective role against severe sepsis
      (P=0.0066, OR 0.6751), whereas haplotype -20G/-44G/-52G served as a risk factor
      for the fatal outcome of severe sepsis (P=0.0052, OR 2.427). These findings
      provide further evidence that beta-defensin 1 may play a role in the pathogenesis
      of severe sepsis.

PMID- 17508031
TI  - Ocular neuroprotection: knowledge gained in translation.

PMID- 17508032
TI  - Proceedings of the International Ocular Neuroprotection Symposium. October 14,
      2006. Toronto, Canada.

PMID- 17508033
TI  - Glaucoma neuroprotection: What is it? Why is it needed?
AB  - The glaucomas are a group of ocular diseases characterized by progressive optic
      nerve damage and visual loss. Although there is good laboratory evidence for
      glaucoma neuroprotection by several drugs, the evidence from randomized clinical
      trials is lacking.

PMID- 17508034
TI  - Preventing blindness in retinal disease: ciliary neurotrophic factor intraocular
      implants.
AB  - A recent phase I trial of an encapsulated cell therapy device that delivers
      ciliary neurotrophic factor has shown the potential of this approach in the
      treatment of retinitis pigmentosa. As experience with this device is gained,
      other retinal degenerative disorders may be potential targets of a similar
      therapeutic approach.

PMID- 17508035
TI  - Axonal loss and neuroprotection in optic neuropathies.
AB  - Most optic neuropathies do not have effective treatments. Examples are ischemic
      optic neuropathy, Leber hereditary optic neuropathy, optic neuritis, and
      traumatic optic neuropathy. In some cases, the pathophysiology of the optic nerve
      injury is not fully understood. For example, while the demyelinative aspects of
      optic neuritis have been studied, the mechanism by which the axonal loss occurs
      is less apparent. In other cases, although the pathophysiology of the optic
      neuropathy may be understood, there is difficulty treating the disease, for
      example, with traumatic optic neuropathy. In response to this therapeutic dearth,
      the concept of neuroprotection has arisen. Neuroprotection is a therapeutic
      paradigm for preventing death of neurons from injury and maintaining function. In
      optic neuropathies, the corresponding neuron is the retinal ganglion cell. These
      cells are unable to divide, and optic neuropathies irrevocably result in their
      death; therefore, the primary target of neuroprotection are retinal ganglion
      cells and their axons. This review emphasizes that most optic neuropathies are
      axonal and thus good targets for neuroprotection.

PMID- 17508036
TI  - Should we treat the brain in glaucoma?
AB  - The loss of retinal ganglion cells in glaucoma may lead to blindness, and current
      therapies are directed at reducing pressure within the eye. Most of the retinal
      ganglion cell axon lies outside the eye, and evidence from experimental primate
      and human glaucoma suggests that axon injury extends from the optic nerve to
      visual pathways in the brain. Neurodegenerative changes in the central visual
      system may contribute to the pathology of glaucomatous progression. Thus,
      intraocular pressure-lowering strategies combined with neuroprotective therapies
      to protect visual neurons in the retina and brain may help to preserve vision in
      patients with glaucoma.

PMID- 17508037
TI  - Special considerations in low-tension glaucoma.
AB  - Low-pressure (low-tension) glaucoma is reviewed in relation to neuroprotection,
      that is, the therapeutic strategy to keep neurons living and functionally
      connected to targets within the brain. Baseline results of the Low-Pressure
      Glaucoma Treatment Study (LoGTS) are reviewed.

PMID- 17508038
TI  - Is this neuroprotective drug good for my glaucoma patients? Some key factors in
      clinical decision-making.
AB  - Neuroprotection protects neurons from death after a primary insult, independent
      of that insult. Important clinical considerations include minimal interference
      with physiological processes, possible simultaneous or sequential treatment
      strategies, and most effective method of drug delivery. Clinicians' assessment of
      the neuroprotective value of any agent hinges on demonstration of efficacy by
      prospective randomized controlled trials. Use of a neuroprotectant will depend on
      the glaucomatous threat to a patient's visual function, as well as the agent's
      therapeutic index and its cost.

PMID- 17508039
TI  - Assessment of the optic disc to measure neuroprotection.
AB  - In early glaucoma, axonal loss and optic disc change occur in the absence of
      detectable changes in psychophysical measurements, such as those obtained from
      standard automated perimetry. Accurate assessment of the anatomy of the optic
      disc is therefore necessary to document change. The measurement of optic disc
      topography with scanning laser ophthalmoscopy has been shown to be accurate,
      reproducible, diagnostically valid, and an accurate reflection of the underlying
      anatomic status of the optic disc and retinal nerve fibre layer. Validated
      techniques have been developed to detect change over time in the surface
      topography of the optic disc. Ultimately, real-time in vivo analysis of the
      health of retinal ganglion cells should provide the best method of assessing the
      advisability and adequacy of treatment and the potential value of neuroprotective
      therapies.

PMID- 17508040
TI  - Natural compounds: evidence for a protective role in eye disease.
AB  - Glaucoma often progresses despite lowering of intraocular pressure (IOP) to
      acceptable or normal levels; it can also develop at normal or even low IOP on the
      basis of non-IOP-dependent risk factors. Therefore, a need exists for therapies
      limiting damage due to glaucoma that are independent of therapies that simply
      lower IOP. The aim of neuroprotection in glaucoma is to slow progression by
      blocking the mechanisms that lead to apoptosis. Many compounds have been
      described as neuroprotective, but the lack of availability of specific
      neuroprotectant compounds and the lack of clinical trials examining the benefits
      of neuroprotective agents for glaucoma limit their current therapeutic use. There
      are, however, many available natural compounds that offer the possibility of
      neuroprotective activity. This review summarizes the potential benefits of
      natural compounds in the treatment of eye disease.

PMID- 17508041
TI  - Modulating the immune system: a vaccine for glaucoma?
AB  - Glaucomatous neuropathy, like other neurodegenerative diseases, is a multi
      dimensional disease in which various molecular and cellular factors contribute to
      the pathological process. These factors, while not initially causative, are key
      elements in disease progression and may continue to contribute even after the
      primary pathology is alleviated. An entire field of research of neuroprotection
      and restoration has opened up as part of the search for additional ways of
      slowing disease progression. We have proposed, on the basis of experimental
      evidence, that a vaccine could be a means of recruiting the immune system to help
      eliminate many of the factors associated with glaucomatous neurodegeneration and
      thus prevent disease progression, though not its onset. This immune defence
      involves lymphocytes, resident and infiltrating innate immune cells, the
      microglia, and macrophages. The antigens of choice are synthetic antigens, such
      as glatiramer acetate, that weakly cross-react with self-antigens in the retina
      and optic nerves. The vaccine induces a beneficial immune response that recruits
      immune effector cells to counteract or neutralize many of the compounds and
      factors that contribute to ongoing destruction, and in addition supports cell
      renewal and repair.

PMID- 17508042
TI  - Stem cells: a source for neuron repair in retinal disease.
AB  - Several features of the eye make it an excellent candidate for cell-based therapy
      to treat corneal and retinal degenerative disease. Corneal and retinal stem cells
      have been identified in the adult human eye. Advances in the stem cell field,
      including methods for cell purification, culture, and molecular characterization,
      have made it easier to manipulate eye stem cells. Moreover, delivery,
      sequestration, tracking, and measurement of outcomes of transplanted cells are
      both feasible and easier for the eye than for other tissues. These factors,
      together with our understanding of the molecular pathways that regulate eye
      development, have resulted in promising results in transplantation of cells to
      the cornea and retina. While there is certainly reason for cautious optimism,
      several obstacles remain before this will ever be a clinical reality, including
      identification of the most appropriate source of stem cells, the long-term
      efficacy of cell transplantation in the context of ongoing disease, and the
      potential of transplanted cells to give rise to tumours.

PMID- 17508043
TI  - Ocular drug delivery: molecules, cells, and genes.
AB  - Recent advances in molecular cell biology have led to the exploration of new
      therapies based on molecules, cells, and genes to treat a variety of ocular
      disorders. In this review, we present the current state of knowledge pertaining
      to the development of different delivery systems to mediate safe and long-lived
      therapies, with an emphasis on gene therapy. The advantages and limitations of
      these delivery and therapeutic methods are also discussed.

PMID- 17508044
TI  - Greek mythology: the eye, ophthalmology, eye disease, and blindness.
AB  - BACKGROUND: In distant eras, mythology was a form of expression used by many
      peoples. A study of the Greek myths reveals concealed medical knowledge, in many
      cases relating to the eye. METHODS: An analysis was made of the ancient Greek
      texts for mythological references relating to an understanding of vision, visual
      abilities, the eye, its congenital and acquired abnormalities, blindness, and eye
      injuries and their treatment. RESULTS: The Homeric epics contain anatomical
      descriptions of the eyes and the orbits, and an elementary knowledge of
      physiology is also apparent. The concept of the visual field can be seen in the
      myth of Argos Panoptes. Many myths describe external eye disease ("knyzosis"),
      visual disorders (amaurosis), and cases of blinding that, depending on the story,
      are ascribed to various causes. In addition, ocular motility abnormalities,
      congenital anomalies (cyclopia), injuries, and special treatments, such as the
      "licking" method, are mentioned. INTERPRETATION: The study of mythological
      references to the eye reveals reliable medical observations of the ancient
      Greeks, which are concealed within the myths.

PMID- 17508045
TI  - [View of the canadian history of corneal transplantation].
AB  - The author presents a brief chronological summary of early attempted corneal
      grafts over the last century culminating in the first successful Canadian
      keratoplasty by Dr. Jean Audet-Lapointe in Montreal on April 20, 1945. Medical
      journals of the day retrace the early experiences at various Canadian medical
      centres with this new innovative surgical procedure. Testimonials from newspaper
      clippings highlight the professional career of Dr. Jean Audet-Lapointe. The role
      and support of the CNIB in Montreal and Toronto in establishing the Canadian Eye
      Bank Service are also presented.

PMID- 17508046
TI  - The definitive story of Buddy Holly's glasses.
AB  - Buddy Holly's glasses were part of his performing identity. Correspondence with
      Dr. J. Davis Armistead, the man who prescribed and sold him those striking
      glasses over 50 years ago, provides the definitive story of Buddy Holly's
      glasses.

PMID- 17508047
TI  - Periocular basal cell carcinoma arising in a site of previous trauma.
AB  - CASE REPORT: We report an incidence of basal cell carcinoma of the lower lid
      arising in an area of trauma 68 years after the initial injury. COMMENTS: Because
      patients may disregard the appearance of a wound in the setting of former trauma,
      medical practitioners need increased suspicion and surveillance of chronic
      nonhealing wounds.

PMID- 17508048
TI  - Merkel cell carcinoma masquerading as a chalazion.
AB  - CASE REPORT: A 62-year-old woman presented with a large rapidly growing
      violaceous mass initially diagnosed as a chalazion. Histopathologic examination
      disclosed Merkel cell carcinoma (MCC). Radiotherapy was not tolerated. Despite
      chemotherapy, she succumbed to widespread metastases 13 months later. COMMENTS:
      MCC must be included in the differential diagnosis of solitary eyelid nodules,
      requiring early and aggressive treatment.

PMID- 17508049
TI  - Ophthalmic findings in Setleis syndrome: two new cases in a mother and son.
AB  - CASE REPORT: Setleis syndrome is a rare ectodermal dysplasia with characteristic
      ophthalmic findings. We describe the first 2 reported cases in Canadian
      individuals of Aboriginal descent. COMMENTS: Although most ophthalmic findings
      are benign, it is important to recognize the clinical significance for management
      and genetic counselling. We postulate an autosomal dominant inheritance in our
      cases.

PMID- 17508050
TI  - Medulloepithelioma masquerading as chronic anterior granulomatous uveitis.
AB  - CASE REPORT: We report a rare clinical case of unilateral ciliary body teratoid
      medulloepithelioma presented first with infantile cataract, subsequently
      masquerading as chronic granulomatous anterior uveitis, followed by appearance of
      a tumour over the iris surface. COMMENTS: Diagnosis of the tumour in the early
      stages allows proper management and avoids enucleation.

PMID- 17508051
TI  - Community-acquired bleb-related endophthalmitis caused by vancomycin-resistant
      enterococci.
AB  - CASE REPORT: We report a case of community-acquired bleb-related endophthalmitis
      caused by vancomycin-resistant enterococci (VRE) in a 79-year-old woman.
      COMMENTS: VRE has usually been considered a nosocomial infection of immune
      compromised patients, but ophthalmologists should be alert to the possibility of
      community-acquired eye infections caused by VRE, particularly in those countries
      with a high VRE community reservoir.

PMID- 17508052
TI  - Localized retinal ischemia as an ocular manifestation of primary antiphospholipid
      syndrome.
AB  - CASE REPORT: Herein, a case of an unusual ocular presentation of primary
      antiphospholipid syndrome. The patient disclosed localized retinal ischemia due
      to branch retinal artery occlusion, confirmed by fluorescein angiography and
      manual perimetry. COMMENTS: The ocular manifestation led to the diagnosis and
      successful treatment of the systemic disease.

PMID- 17508053
TI  - Primary liposarcoma of the orbit: a report of two cases.
AB  - CASE REPORT: Only 21 cases of primary orbital liposarcoma have been previously
      published. We report two such rare cases in a 50-year-old man and a 40-year-old
      woman. COMMENTS: The diagnosis is usually established after histopathologic
      examination. This paper also describes clinical and radiologic features and gives
      a brief review of the literature.

PMID- 17508055
TI  - More ophthalmologists (Ophthalmology human resource projections: are we heading
      for a crisis in the next 15 years? Vol. 42(1)).

PMID- 17508056
TI  - Nature's shell game revealed: evidence for non-Newtonian laterality of macular
      vision (Ocular integration in the human visual cortex. Vol. 41(5)).

PMID- 17508057
TI  - Giant cell arteritis presenting with hemianopic visual field loss.

PMID- 17508058
TI  - Acute hypertension due to phenylephrine eyedrops in a newborn.

PMID- 17508059
TI  - Posttraumatic endophthalmitis due to a rare pathogen, Alcaligenes faecalis.

PMID- 17508060
TI  - Recurrent capsular opacification after Nd:YAG laser treatment in myotonic
      dystrophy.

PMID- 17508061
TI  - Retinoblastoma presenting as spontaneous hyphema.

PMID- 17508062
TI  - Bilateral toxic anterior segment syndrome after cataract surgery.

PMID- 17508063
TI  - In memoriam: J. Clement McCulloch.

PMID- 17508067
TI  - W. Bruce Jackson.

PMID- 17508069
TI  - Congenital epulis of the newborn: a case report.
AB  - Congenital epulis of the newborn is a rare soft tissue manifestation that affects
      infants, involving predominantly the maxillary ridge. When identified, generally
      at birth, excisional biopsy is recommended to avoid feeding and respiratory
      disturbances. This article presents a case report of a female infant who was
      referred to an oral and maxillofacial surgery facility for removal of a fibrotic
      mass present on the mandibular alveolar ridge. Diagnosis and prompt intervention
      can prevent expected complications such as failure to thrive or respiratory
      difficulty. Pediatric and general dentists should be familiar with oral
      pathologies that may affect the newborn or infants so that early diagnosis and
      treatment can be accomplished.

PMID- 17508070
TI  - Effect of welding parameters on penetration of Nd:YAG laser into cast Ti and Au-
      and Ag-based alloys.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of laser
      welding parameters (current [A], spot diameter [mm], and pulse duration [ms]) on
      the weld penetration depth by Nd:YAG laser into cast titanium and Ag-based and Au
      based alloys. METHOD AND MATERIALS: Two cast blocks of each metal were laser
      welded with various parameters at their interface. The blocks were then
      separated, and the penetration depth into each metal was measured on the
      separated surface using a computer program. The data were statistically analyzed.
      RESULTS: Increasing the current and decreasing the spot diameter increased the
      penetration depth into each alloy. No statistical differences in penetration
      depth were found for each metal among the pulse durations. CONCLUSION: The
      results suggested that, regardless of the pulse duration, the current and the
      spot diameter in relation to the power density (W/cm2) of the laser affected the
      weld penetration depth into each metal. Cast titanium produced more penetration
      depth compared to gold alloys because of its low thermal conductivity value and
      high rate of laser beam absorption.

PMID- 17508071
TI  - Effect of alcohol and unfilled resin in the incremental buildup of resin
      composite.
AB  - OBJECTIVE: The purpose of this in vitro study was to investigate the effect of
      isopropyl alcohol and unfilled resin on the flexural strength of incrementally
      layered resin-based composite beams. METHOD AND MATERIALS: Five groups of 30
      composite beams were fabricated in a 2 3 2 3 24-mm Teflon split-mold: group 1
      (control group), a homogeneous resin composite beam; group 2, 2 increments with
      an air-inhibited layer between the increments; group 3, 2 increments with a Mylar
      strip placed against the composite interface during polymerization of the first
      increment; group 4, 2 increments with the first increment contoured with an
      isopropyl alcohol (70%) lubricated instrument; and group 5, 2 increments with the
      first increment contoured with unfilled resin lubricating the application
      instrument. Each increment was polymerized for 40 seconds on both front and back
      surfaces. The flexural strength of the composite specimens was determined using 4
      point bending in an Instron universal testing machine. RESULTS: The mean flexural
      strength in MPa and standard deviation were as follows: group 1: 142.5 (17.3);
      group 2: 98.2 (15.2); group 3: 105.9 (16.3); group 4: 103.4 (19.4); and group 5:
      106.1 (21.3). One-way analysis of variance detected a statistically significant
      difference among the groups (P < .001). Tukey's HSD post hoc tests determined
      that only group 1 was significantly different from the other 4 groups.
      CONCLUSION: The use of isopropyl alcohol and unfilled resin as instrument
      lubricants for incremental composite buildup seems to have little effect on the
      flexural strength of light-cured composite.

PMID- 17508072
TI  - Dentin bonding of light- and self-curing resin composites using simplified total-
      and self-etch adhesives.
AB  - OBJECTIVE: The purpose of this study was to evaluate the influence of (1) the
      curing mode of resin composites and (2) activators for dual curing of the bonding
      on dentin bond strength. METHODS: The light-curing resin composite Brilliant (B)
      and the self-curing resin composite Brilliant MH were bonded with the following
      adhesives (n = 10): OptiBond FL, Excite, Prime&Bond NT, OptiBond Solo Plus, Adper
      Prompt L-Pop, Clearfil SE Bond, Xeno III, and AdheSE. Excite, Prime&Bond NT, and
      OptiBond Solo Plus were also used in combination with activators for dual curing.
      Tensile bond strengths were measured after 24 hours of water storage (37 degrees
      C), and fractured surfaces were analyzed in the scanning electron microscope.
      RESULTS: Except for Excite/dual curing and Prime&Bond NT/dual curing, bond
      strengths with Brilliant MH were significantly lower than with Brilliant.
      Activators significantly increased bond strengths in Excite/Brilliant MH, but not
      in Prime&Bond NT/Brilliant MH and OptiBond Solo/Brilliant MH. CONCLUSIONS: This
      study confirms the incompatibility between self-curing resin composites and
      simplified bonding systems containing acidic components. Activators for dual
      curing the bonding eliminated this chemical incompatibility only in 2 of 3
      bonding systems. The use of these activators in combination with light-curing
      resin composites must be avoided.

PMID- 17508073
TI  - Dental findings in a child with glycogen storage disease type IA.
AB  - Glycogen storage disease type I, also known von Gierke's disease, is a rare,
      severe autosomal recessive disorder due to a defect in liver, kidney, and
      intestinal mucosa. The existence of delayed development of the dentition,
      increased incidence of dental caries, taurodontism, and prolonged bleeding
      following dental procedures should lead clinicians to consider type I glycogen
      storage disease. A 10-year-old boy with glycogen storage disease type I whose
      condition was first diagnosed when he was 4 years of age, was referred to the
      clinic for multiple caries and evaluation of delayed tooth eruption. On physical
      examination, the patient was cooperative, with short stature, protuberant
      abdomen, and growth retardation. Laboratory findings indicated that blood levels
      of pyruvate, triglycerate, uric acid, and cholesterol were elevated. Intraorally
      delayed mixed dentition was evident, and approximal caries were found in teeth
      55, 54, 52, 51, 61, 62, 65, 74, 84, and 85. The most significant radiographic
      finding was consistent with taurodontism of the molar teeth. Lateral and
      posteroanterior cephalometric films showed that dimensions of the craniofacial
      complex were strongly reduced. Evaluation of the patient's dental age was
      approximately 6 years.

PMID- 17508074
TI  - Subjective and photometric determination of bleaching outcomes.
AB  - OBJECTIVE: Subjective and objective measures were used to determine the relative
      efficacy of 10% and 35% carbamide peroxide gels in bleaching extracted human
      teeth. METHOD AND MATERIALS: Fifty-five teeth (premolars and molars) were
      sectioned longitudinally, and one-half of each tooth was assigned to group A
      (10%) and the other half to group B (35%). Prebleaching shades were evaluated
      subjectively by 5 experienced observers using standard shade tabs. Photographs
      were also taken with a calibrated digital camera. Luminosity, R, G, and B levels
      were determined with Photoshop software. The specimens were then bleached by
      either 10% or 35% carbamide peroxide, after which they were reexamined by the 5
      observers and rephotographed. RESULTS: All bleached specimens were subjectively
      assessed as "lighter", but there was no perceived difference in final shade
      between groups. Objective measurement showed that the greatest spread in the 0 to
      255 scales was in the B levels. Mean (and range) of pre- and postbleaching B
      levels and their differences, by group, were group A, 96.2 (76.5 to 117.1), 113.6
      (87.7 to 129.1), difference 17.4, and group B, 95.4 (72.1 to 118.8), 110.5 (88.0
      to 138.5), difference 15.1. Statistics were performed using paired t tests. These
      pre- and postbleaching differences were significant (P < .002). The difference
      between mean postbleaching B values was not significant (P = .479). The greatest
      change in luminosity occurred in initially dark teeth treated with 35% carbamide
      peroxide (P = .036). CONCLUSIONS: Subjective determinations suggest that the
      bleaching protocols tested were equally effective, but the objective measurements
      implied that the higher concentration of carbamide peroxide was more effective
      for darker teeth.

PMID- 17508075
TI  - Prosthetic and orthodontic rehabilitation of a patient with missing maxillary
      lateral incisors: a case report.
AB  - IPS Empress 2 materials can be used for fabrication of short-span fixed partial
      dentures in the anterior region as well as single crowns. This clinical report
      describes the prosthodontic treatment of a 16-year-old male patient with missing
      permanent maxillary left and right incisors with IPS Empress 2 fixed partial
      dentures following orthodontic treatment.

PMID- 17508076
TI  - Questions and answers on titanium-ceramic dental restorative systems: a
      literature study.
AB  - OBJECTIVE: Titanium ceramics has become a topic of interest for prosthetic
      applications, thanks to the documented biocompatibility of commercially pure
      titanium. A number of concepts have been presented, including metal frameworks
      produced by casting or milling and a number of materials and methods for
      veneering. However, the concept has not reached a clinical breakthrough since
      failures have been reported from clinical experiences. METHOD AND MATERIALS: A
      PubMed search on the following key words was performed: titanium ceramics, long
      term results. RESULTS: This review illustrates the fact that it is possible to
      have success with titanium ceramics on crucial criteria: fit and marginal
      adaptation, bond strength between metal and ceramics, and esthetic outcome. A
      review of clinical studies indicates a tendency for success rates to increase
      with time, which must be explained as a normal learning curve for a technical
      concept. The learning curve also includes development of materials and methods
      and the fact that there is a certain amount of technique sensitivity involved in
      the success rate for titanium ceramics. CONCLUSIONS: There is reason to believe
      that the outstanding clinical properties of titanium will further catalyze the
      development of titanium ceramics, and recent experiences clearly indicate that
      titanium ceramics, being a clinical product ready for use in fixed partial
      dentures, might already today challenge standard metal ceramics.

PMID- 17508077
TI  - Combined treatment approach of gingivectomy and CO2 laser for cyclosporine
      induced gingival overgrowth.
AB  - The aim of this report is to present a combined treatment approach with
      gingivectomy and CO2 laser for the management of cyclosporine-induced gingival
      overgrowth in 4 cases. Four renal transplant patients were surgically treated for
      marked gingival overgrowth by means of gingivectomy and CO2 laser.
      Postoperatively, all patients were followed for bleeding, pain, infection during
      the early healing period, and recurrence of gingival overgrowth for 12 months.
      The healing was uneventful, and no signs of bleeding, postoperative pain, or
      infection were observed in any patient during the early healing period. In the
      12th postoperative month, there was evidence of mild recurrence in 1 patient,
      while no sign of recurrence was observed in the other patients during the follow
      up period. The advantages of this combined technique include satisfactory
      bleeding control and clear visibility during the procedure, as well as reduced
      postoperative pain and swelling.

PMID- 17508079
TI  - An introduction to bubble dynamics.
AB  - The creation, understanding and control of mesoscopic chemical objects are at the
      core of many areas of chemistry and physics. Their preparation depends on a
      variety of nucleation and aggregation processes and they are exploitable for
      practical purposes, including fabrication techniques. At the opposite end, are
      cavitation phenomena. They also originate from a nucleation event, but result in
      the formation of a bubble. In recent years, bubbles have ceased to be a problem
      and have become increasingly more attractive for medical and industrial
      applications. Our understanding of bubble dynamics has steadily increased and we
      believe that it is timely to attempt to summarize in simple terms the knowledge
      accumulated in this area for a chemical audience. In this introduction, we focus
      on the nature of bubble formation, evolution and collapse. We discuss the
      macroscopic models that were developed at the beginning of the 20th century and
      accompany them with the results of more detailed molecular dynamics simulations.

PMID- 17508078
TI  - Restorative caries therapy in nursing home residents using composite resins and
      compomers without a rubber dam.
AB  - OBJECTIVE: This study was designed to investigate the prognosis of restorative
      caries therapy applied in nursing home residents. METHOD AND MATERIALS: In 25
      consecutive patients a total of 42 restorations were placed, 23 of composite
      resin (APX/SE Bond) and 19 of compomer (Dyract). The working conditions, such as
      patient cooperation, quantity of saliva, location of cavity margins, cavity size,
      and gingival inflammation, were evaluated prior to treatment. The restorations
      were evaluated qualitatively at baseline, after 6 months, and after 12 months.
      RESULTS: At 12 months, all examined restorations were clinically acceptable (6
      patients had died). There was no significant difference between the quality of
      the restorations in composite resin and compomer. The plaque scores increased
      significantly during the study period. CONCLUSIONS: The study showed that, within
      the limitation of a short-term follow-up, restorative caries therapy using
      composite resin or compomer was successful in nursing home residents although
      rubber dam was not used.

PMID- 17508080
TI  - Application of valence-bond techniques to the study of weakly bound complexes.
      The potential energy surface of the Ne-CH(4) system.
AB  - We present a comprehensive survey of the Molecular Orbital-Valence Bond (MO-VB)
      method, a theoretical scheme developed within the framework of the Valence Bond
      theory to deal with weakly bound intermolecular complexes. According to the MO
      VB, the wavefunction of the system is expressed as a truncated non-orthogonal
      Configuration Interaction expansion, which is size extensive and a priori free of
      basis set superposition error. We report on the recent developments of the
      method, which extend the range of application of the MO-VB to intermolecular
      complexes with a quite large number of correlated electrons, showing that VB
      based methods are nowadays a valid alternative to Molecular Orbital approaches
      also in this field. The MO-VB has been applied to study extensively the Ne-CH(4)
      complex, and compared with the more standard MP4 and CCSD(T) results. We
      determined two analytical Potential Energy Surfaces (PES) for this system,
      computed at MO-VB and MP4 level, which represent the first ones coming entirely
      from ab initio computations. The features of our potentials are discussed, and
      compared to the single analytical potential which includes the anisotropy
      available in the literature, determined about twenty years ago by Udo Buck and co
      workers using a semiempirical approach [U. Buck, A. Kolhase, D. Secrest, T.
      Phillips, G. Scoles and F. Grein, Mol. Phys., 1985, 55, 1233]. The differences
      among the three PES are quite relevant, and are due to play a relevant role in
      the theoretical simulations of the dynamical properties of the Ne-CH(4) system.

PMID- 17508081
TI  - Femtosecond quantum control of molecular dynamics in the condensed phase.
AB  - We review the progress in controlling quantum dynamical processes in the
      condensed phase with femtosecond laser pulses. Due to its high particle density
      the condensed phase has both high relevance and appeal for chemical synthesis.
      Thus, in recent years different methods have been developed to manipulate the
      dynamics of condensed-phase systems by changing one or multiple laser pulse
      parameters. Single-parameter control is often achieved by variation of the
      excitation pulse's wavelength, its linear chirp or its temporal subpulse
      separation in case of pulse sequences. Multiparameter control schemes are more
      flexible and provide a much larger parameter space for an optimal solution. This
      is realized in adaptive femtosecond quantum control, in which the optimal
      solution is iteratively obtained through the combination of an experimental
      feedback signal and an automated learning algorithm. Several experiments are
      presented that illustrate the different control concepts and highlight their
      broad applicability. These fascinating achievements show the continuous progress
      on the way towards the control of complex quantum reactions in the condensed
      phase.

PMID- 17508082
TI  - The binding of nitric oxide at the Cu(i) site of copper nitrite reductase and of
      inorganic models: DFT calculations of the energetics and EPR parameters of side
      on and end-on structures.
AB  - Density functional theory calculations have been used to probe the end-on and
      side-on bonding motifs of nitric oxide at the Cu(i) centre in the enzyme copper
      nitrite reductase and in three inorganic model systems. We find that irrespective
      of a range of functionals used, the end-on structure is preferred by up to 40 kJ
      mol(-1), although this preference is smaller for the enzyme than for the
      inorganic model systems. We have calculated the g-tensor and atomic hyperfine
      coupling constants for these structures. When compared to available experimental
      data, for one model compound the calculated EPR parameters definitely favour an
      end-on structure, although this preference is somewhat less for the enzyme. Our
      prediction of NO end-on binding in the enzyme is at variance with structural
      data.

PMID- 17508083
TI  - Energy-directed tree search: an efficient systematic algorithm for finding the
      lowest energy conformation of molecules.
AB  - We present a new systematic algorithm, energy-directed tree search (EDTS), for
      exploring the conformational space of molecules. The algorithm has been designed
      to reliably locate the global minimum (or, in the worst case, a structure within
      4 kJ mol(-1) of this species) at a fraction of the cost of a full conformational
      search, and in this way extend the range of chemical systems for which accurate
      thermochemistry can be studied. The algorithm is inspired by the build-up
      approach but is performed on the original molecule as a whole, and objectively
      determines the combinations of torsional angles to optimise using a learning
      process. The algorithm was tested for a set of 22 large molecules, including open
      and closed-shell species, stable structures and transition structures, and
      neutral and charged species, incorporating a range of functional groups (such as
      phenyl rings, esters, thioesters and phosphines), and covering polymers,
      peptides, drugs, and natural products. For most of the species studied the global
      minimum energy structure was obtained; for the rest the EDTS algorithm found
      conformations whose total electronic energies are within chemical accuracy from
      the true global minima. When the conformational space is searched at a resolution
      of 120 degrees , the cost of the EDTS algorithm (in its worst-case scenario)
      scales as 2(N) for large N (where N is the number of rotatable bonds), compared
      with 3(N) for the corresponding systematic search.

PMID- 17508084
TI  - On the sigma,pi-energy separation of the aromatic stabilization energy of
      cyclobutadiene.
AB  - The separation of the aromatic stabilization energy (ASE) of cyclobutadiene (CBD)
      into a sigma- and a pi-component is reinvestigated. Eight different reactions are
      considered for this purpose. As expected, the total destabilization energies that
      result from these reactions depend only on the reference compound and not on the
      reaction itself. The heats of formation that can be obtained from the calculated
      reaction energies are in excellent agreement with the recently determined
      experimental value of 102.3 +/- 3.8 kcal mol(-1) (A. Fattahi, L. Liz, Z. Thian
      and S. R. Kass, Angew. Chem., Int. Ed., 2006, 45, 4984-4988). Evaluation of the
      angular strain in CBD from a newly considered reaction confirms earlier estimates
      and yields a strain energy of 34 +/- 3 kcal mol(-1). If referred to s-cis
      butadiene this leads to an ASE of -37 +/- 4 kcal mol(-1) in close agreement with
      estimates provided by A. Fattahi, L. Liz, Z. Thian and S. R. Kass, Angew. Chem.,
      Int. Ed., 2006, 45, 4984-4988; and by K. B. Wiberg, Chem. Rev., 2001, 101, 1317
      1332. With s-trans-butadiene as reference we obtain -42 +/- 4 kcal mol(-1). This
      value is 8 to 10 kcal mol(-1) less destabilizing than recent estimates of A. A.
      Deniz, K. S. Peters and G. J. Snyder, Science, 1999, 286, 1119-1112; and
      Kovacevic, D. Baric, Z. B. Maksic, T. Muller, J. Phys. Chem. A, 2004, 108, 9126
      9133. Attempts to separate ASE(CBD) and E(strain)(CBD) into a sigma- and a pi
      component do not lead to useful results. In contrast to ASE and E(strain)
      themselves, the sigma- and pi-components depend strongly on the applied reaction.
      A detailed analysis reveals that it is not possible to associate these components
      with only one of the molecules that participate in the reaction. The components
      depend on all of these molecules and therefore on the underlying reaction.
      Generally, components that result from a formal sigma,pi-energy separation of
      aromatic stabilization energies or strain energies cannot be considered as the
      sigma- and pi-components of these energies.

PMID- 17508085
TI  - Effect of Ni(ii), Cu(ii) and Zn(ii) association on the keto-enol tautomerism of
      thymine in the gas phase.
AB  - The effect of Ni(II), Cu(II) and Zn(II) association on the diketo/keto-enol
      tautomerism of thymine has been investigated through the use of B3LYP density
      functional theory calculations. Final energies were obtained at the B3LYP/6
      311+G(2df,2p)//B3LYP/6-311+G(d,p) level of theory. Ni(II) and Cu(II) lead to an
      oxidation of thymine which for Zn(ii) is only partial and catalyze the
      tautomerization process, this catalytic effect being much larger for Ni(2+) and
      Zn(2+) than for Cu(2+). One of the most significant consequences of the oxidation
      of the base is that the calculated BDE's are primarily dictated by the value of
      the second ionization potential of the metal, and therefore follow the sequence
      Cu(2+) > Ni(2+) > Zn(2+). Also importantly, metal dication association leads to a
      stabilization of the keto-enol tautomer, which becomes the most stable form upon
      interaction with Ni(2+) and Zn(2+). This stabilization enhancement is the
      consequence of three concomitant factors, namely, (i) a stronger interaction of
      the metal cation with the carbonyl oxygen, (ii) the interaction of the metal with
      the dehydrogenated ring nitrogen, (iii) an aromatization of the six-membered
      ring.

PMID- 17508086
TI  - Adiabatic and non-adiabatic corrections to rovibrational energies of diatomic
      molecules: variational calculations with experimental accuracy.
AB  - Using the variational technique, eigensolutions of the radial Herman-Asgharian
      equation accounting for non-adiabatic terms are determined within the
      experimental accuracy of the high-resolution spectroscopy. This method, which is
      independent of the algebraic and numerical approaches currently used in the
      literature for a "direct-potential-fit" of diatomic rovibrational spectra, is
      shown to be useful for validation of available calculations and for resolving
      some controversial issues. Comparative discussions are reported in this paper for
      a dozen diatomic molecules.

PMID- 17508087
TI  - Infrared spectroscopy and structure of photochemically protonated biomolecules in
      the gas phase: a noradrenaline analogue, lysine and alanyl alanine.
AB  - A novel photochemical technique combined with mass spectrometry and resonant
      infrared multiphoton dissociation spectroscopy (R-IRMPD) has been used to record
      infrared vibrational spectra of the free protonated noradrenaline analogue, 2
      amino-1-phenylethanol (APE-H(+)), the amino acid, lysine (Lys-H(+)), and the
      dipeptide, alanyl alanine (Ala-Ala-H(+)) in the gas phase. Coupling their
      spectra, obtained in the OH, NH and CH stretch regions, with ab initio
      calculations has allowed assignment of their preferred protonation sites and
      conformations. This simple technique will have wide applicability in future
      investigations of protonated biomolecular structure and conformation.

PMID- 17508088
TI  - Mechanistical studies on the formation of isotopomers of hydrogen peroxide
      (HOOH), hydrotrioxy (HOOO), and dihydrogentrioxide (HOOOH) in electron-irradiated
      H(2)(18)O/O(2) ice mixtures.
AB  - In order to investigate the chemical reactions inside water-oxygen ice mixtures
      in extreme environments, and to confirm the proposed reaction mechanisms in pure
      water ice, we conducted a detailed infrared spectroscopy and mass spectrometry
      study on the electron irradiation of H(2)(18)O/O(2) ice mixtures. The formation
      of molecular hydrogen, isotopically substituted oxygen molecules (18)O(18)O and
      (16)O(18)O, ozone ((16)O(16)O(16)O, (16)O(16)O(18)O, and (16)O(18)O(16)O),
      hydrogen peroxide (H(18)O(18)OH, H(16)O(16)OH and H(16)O(18)OH), hydrotrioxy
      (HOOO), and dihydrogentrioxide (HOOOH) were detected. Kinetic models and reaction
      mechanisms are proposed to form these molecules in water and oxygen-rich solar
      system ices.

PMID- 17508089
TI  - Theoretical and experimental determination of the electronic structure of
      V(2)O(5), reduced V(2)O(5-x) and sodium intercalated NaV(2)O(5).
AB  - In this work the electronic structure of V(2)O(5), reduced V(2)O(5-x)
      (V(16)O(39)) and sodium intercalated NaV(2)O(5) has been studied by both
      theoretical and experimental methods. Theoretical band structure calculations
      have been performed using density functional methods (DFT). We have investigated
      the electron density distribution of the valence states, the total density of
      states (total DOS) and the partial valence band density of states (PVBDOS).
      Experimentally, amorphous V(2)O(5) thin films have been prepared by physical
      vapour deposition (PVD) on freshly cleaved highly oriented pyrolytic graphite
      (HOPG) substrates at room temperature with an initial oxygen understoichiometry
      of about 4%, resulting in a net stoichiometry of V(2)O(4.8). These films have
      been intercalated by sodium using vacuum deposition with subsequent spontaneous
      intercalation (NaV(2)O(5)) at room temperature. Resonant V3p-V3d photoelectron
      spectroscopy (ResPES) experiments have been performed to determine the PVBDOS
      focusing on the calculation of occupation numbers and the determination of
      effective oxidation state, reflecting ionicity and covalency of the V-O bonds.
      Using X-ray absorption near edge spectra (XANES) an attempt is made to visualize
      the changes in the unoccupied DOS due to sodium intercalation. For comparison
      measurements on nearly stoichiometric V(2)O(5) single crystals have been
      performed. The experimental data for the freshly cleaved and only marginally
      reduced V(2)O(5) single crystals and the NaV(2)O(5) results are in good agreement
      with the calculated values. The ResPES results for V(2)O(4.8) agree in principle
      with the calculations, but the trends in the change of the ionicity differ
      between experiment and theory. Experimentally we find partly occupied V 3d states
      above the oxygen 2p-like states and a band gap between these and the unoccupied
      states. In theory one finds this occupation scheme assuming oxygen vacancies in
      V(2)O(5) and by performing a spin-polarized calculation of an antiferromagnetic
      ordered NaV(2)O(5.).

PMID- 17508090
TI  - Quantum chemical and vibrational investigation of sodium exchanged gamma-alumina
      surfaces.
AB  - The sodium cation is well known as an efficient poison of gamma-alumina surface
      acidity. This poisoning effect has been revealed both by characterization methods
      and catalytic tests. In this work, we propose an accurate model of sodium
      exchanged gamma-alumina surfaces. On realistic models of hydroxylated gamma
      alumina surfaces, the location of sodium cation is determined by the use of
      density functional theory (DFT) methods. For the (100) and (110) surfaces of
      gamma-alumina, the sodium cation is found in a solvated state within an inner
      solvation sphere complex. Its coordination sphere is constituted by O-mu(2), O
      mu(3) and HO-mu(1) surface groups. The stretching frequency of these HO-mu(1)
      groups is shifted, leading to the appearance of a new band predicted and observed
      at about 3754 cm(-1) on the IR spectrum.

PMID- 17508091
TI  - Metabolic acidosis in childhood: why, when and how to treat.
AB  - OBJECTIVES: To critically discuss the treatment of metabolic acidosis and the
      main mechanisms of disease associated with this disorder; and to describe
      controversial aspects related to the risks and benefits of using sodium
      bicarbonate and other therapies. SOURCES: Review of PubMed/MEDLINE, LILACS and
      Cochrane Library databases for articles published between 1996 and 2006 using the
      following keywords: metabolic acidosis, lactic acidosis, ketoacidosis, diabetic
      ketoacidosis, cardiopulmonary resuscitation, sodium bicarbonate, treatment.
      Classical publications concerning the topic were also reviewed. The most recent
      and representative were selected, with emphasis on consensus statements and
      guidelines. SUMMARY OF THE FINDINGS: There is no evidence of benefits resulting
      from the use of sodium bicarbonate for the hemodynamic status, clinical outcome,
      morbidity and mortality in high anion gap metabolic acidosis associated with
      lactic acidosis, diabetic ketoacidosis and cardiopulmonary resuscitation.
      Therefore, the routine use of sodium bicarbonate is not indicated. Potential side
      effects must be taken into consideration. Treating the underlying disease is
      essential to reverse the process. The efficacy of other alternative therapies has
      not been demonstrated in large-scale studies. CONCLUSIONS: Despite the known
      effects of acidemia on the organism in critical situations, a protective role of
      acidemia in hypoxic cells and the risk of alkalemia secondary to drug
      interventions are being considered. There is consensus regarding the advantages
      of alkali and sodium bicarbonate therapy in cases with normal anion gap; however,
      in the presence of high anion gap acidosis, especially lactic acidosis, diabetic
      acidosis and cardiopulmonary resuscitation, the use of sodium bicarbonate is not
      beneficial and has potential adverse effects, limiting its indication. The only
      points of agreement in the literature refer to the early treatment of the
      underlying disease and the mechanisms generating metabolic acidemia. Other
      promising treatment alternatives have been proposed; however, the side effects
      and absence of controlled studies with pediatric populations translate into lack
      of evidence to support the routine use of such treatments.

PMID- 17508092
TI  - Conventional mechanical ventilation in pediatrics.
AB  - OBJECTIVE: To review the various challenges of providing mechanical ventilation
      to pediatric patients with diseases of increased airway resistance, diseases of
      abnormal lung compliance or normal lungs. SOURCES: Original data from our
      pediatric intensive care unit and animal research laboratory. Relevant articles
      included in the MEDLINE electronic database during the last 10 years. Also
      included were book chapters and definitive studies, as judged by the authors, in
      the fields of asthma, acute respiratory distress syndrome, mechanical
      ventilation, ventilator-induced lung injury and permissive hypercapnia. SUMMARY
      OF THE FINDINGS: Mechanical ventilation of patients with diseases of increased
      airway resistance should center on avoidance of dynamic hyperinflation, allowing
      complete exhalation prior to the initiation of a subsequent breath and permissive
      hypercapnia. Positive end-expiratory pressure should be used sparingly to prevent
      atelectasis and facilitate synchrony in spontaneously breathing patients.
      Mechanical ventilation of patients with diseases of abnormal lung compliance
      should take into consideration the inhomogeneous distribution of lung disease.
      Focus should be on avoidance of volutrauma and atelectrauma that could result in
      ventilator-associated lung injury. CONCLUSIONS: The last decade was marked by
      significant advances in the management of pediatric respiratory failure. The
      choice of mechanical ventilation strategy can significantly influence the
      subsequent course of lung injury. Mechanical ventilation can no longer be viewed
      simply as a harmless support modality that is employed to keep patients alive
      while disease-specific treatments are used to ameliorate the underlying
      pathology.

PMID- 17508093
TI  - The new guidelines for cardiopulmonary resuscitation: a critical analysis.
AB  - OBJECTIVE: To describe the new American Heart Association (AHA) guidelines for
      pediatric life support, based on the scientific evidence evaluated by the
      International Liaison Committee on Resuscitation, and endorsed and disseminated
      by North American resuscitation councils. SOURCES: The guidelines for basic and
      advanced life support published in Circulation in November 2005 were reviewed
      together with subsequent publications on the same topics, identified in PubMed
      and MEDLINE using the keywords cardiac arrest, basic life support, advanced life
      support, cardiopulmonary resuscitation and pediatric resuscitation. SUMMARY OF
      THE FINDINGS: The greatest guideline changes are in the area of basic life
      support. The new guidelines emphasize the new chest compression/ventilation ratio
      for trained health professionals, which is now 15:2 for all children except
      neonates. Also emphasized is the need for harder and faster chest compressions,
      and the need to avoid hyperventilation during and after cardiorespiratory arrest.
      The use of high-dose epinephrine has been removed, as have some other previous
      recommendations. CONCLUSIONS: The most recent AHA guidelines for pediatric
      resuscitation are focused primarily on basic life support care. They are based on
      the best available scientific evidence, although further research is required to
      validate these changes and provide new evidence for future guidelines.

PMID- 17508094
TI  - Comparison of transcutaneous and plasma bilirubin measurement.
AB  - OBJECTIVES: To compare transcutaneous bilirubin measurements made using Bilicheck
      equipment with assays of capillary plasma using the Unistat bilirubinometer
      (Leica). METHODS: Two hundred concomitant assays were performed (transcutaneous
      and in plasma), and the correlation and level of agreement between them was
      calculated. An assessment was also made of the influence of birth weight, skin
      color, gestational age, postnatal age and phototherapy. RESULTS: The linear
      correlation coefficient was 0.92, and the mean difference between assays was 0.72
      (+/-1.57) mg/dL, with a 95% confidence interval from -2.42 to +3.86. The best of
      a series of ROC curves demonstrated that transcutaneous assays at 14 mg/dL offer
      the best sensitivity (88.2%) and specificity (97.8%), with a positive predictive
      value of 78.9%, negative predictive value of 98.9 and are below the curve of
      0.98. CONCLUSIONS: Assays performed using Bilicheck can be substituted for
      capillary plasma assays up to 14 mg/dL. Above this level the device should only
      be used for screening for patients whose bilirubin should be assayed in blood.

PMID- 17508095
TI  - The effects of exposing rats to cigarette smoke on milk production and growth of
      offspring.
AB  - OBJECTIVES: To analyze the effects of exposure to cigarette smoke during
      gestation and lactation on the milk production of rats and on the weight gain and
      linear growth of their offspring. METHODS: Three groups of female rats were
      studied during gestation and lactation: 15 rats were exposed to cigarette smoke
      and air flow, 18 rats were handled, i.e., exposed to compressed air flow, and 18
      rats were used as controls. Newborn rats were measured and weighed every 5 days,
      from the first to the 15th day. Milk production was estimated by 1-hour milk
      extraction and weight gained by litters. RESULTS: The offspring of rats exposed
      to cigarette smoke weighed less and were shorter at birth. During lactation, the
      offspring of rats exposed to smoke and also of rats that had merely been handled
      gained less weight than the control group. Milk production gauged by the 1-hour
      extraction method was reduced in the group exposed to smoke and, to a lesser
      extent, also in the group that had been handled. Milk production estimated
      according to the pups' weight gain was reduced equally in the groups exposed to
      smoke and merely handled, when compared to the control group. CONCLUSIONS:
      Exposure to cigarette smoke compromised the birth weight and birth length, but
      during lactation, handling also compromised weight gain of offspring. Handling
      and, to a greater extent, exposure to tobacco, were prejudicial to milk
      production.

PMID- 17508096
TI  - Measurement of body composition changes with weight loss in postmenopausal women:
      comparison of methods.
AB  - BACKGROUND: The accurate measurement of body composition changes is important
      when evaluating the efficacy of medical nutrition therapy and weight management
      programs, yet is not well documented in older women. OBJECTIVE: We compared
      methods of estimating energy-restriction-induced body composition changes in
      postmenopausal women. DESIGN: 27 women (59 +/- 8 y; BMI 29.0 +/- 2.9 kg/m2; mean
      +/- SD) completed a 9-wk energy restriction period (5233 kJ/d, (1250 kcal/d)).
      Changes in % body fat (delta%BF), fat mass (deltaFM), and fatfree mass (deltaFFM)
      were measured by hydrostatic weighing (HW), air-displacement plethysmography
      (ADP), dual-energy x-ray absorptiometry (DXA), and deuterium oxide dilution
      (D2O). The Baumgartner et al. (Am J Clin Nutr 53:1345-1353, 1991) four
      compartment (4C) model with body volume from HW was the criterion method. The 4C
      model with body volume from ADP was also compared. Regression equations were
      developed based on 4CHW (dependent variable) utilizing results of change (POST
      PRE) for each method. RESULTS: The women lost 6.8 +/- 3.2 kg; 9% of baseline
      weight. Based on 4CHW, the body composition changes were -2.4 +/- 4.5 delta%BF, 
      4.7 +/- 3.3 kg deltaFM, and -2.6 +/- 4.4 kg deltaFFM. No differences were
      detected by ANOVA for delta%BF, deltaFM, and deltaFFM among 4CHW, HW, ADP, DXA,
      D2O, and 4CADP. Bland-Altman limits of agreement showed differences between
      methods that ranged from 14.5 to -14.1 delta%BF, 7.8 to -8.1 kg deltaFM, and 7.5
      to -8.4 kg deltaFFM for individuals. A bias was shown with 4CADP overestimating
      delta%BF (1.4 %) and FM (0.6 kg) and underestimating deltaFFM (-1.2 kg) compared
      to 4CHW. The regression model was acceptable for %BF (4CADP, 2CHW, and 2CD2O); FM
      and FFM (4CADP, 3CDXA, 2CHW, and 2CD2O), but not for other estimates of %BF, FM,
      FFM. CONCLUSIONS: These body composition assessment methods may be used
      interchangeably to quantify changes in % body fat, fat mass, and fat-free mass
      with weight loss in groups of postmenopausal women. 4CADP overestimates delta%BF
      and underestimates deltaFFM. When utilizing one of these comparison methods
      (4CADP, 3CDXA, 2CHW, 2CD2O) to quantify changes in fat mass and fat-free mass for
      an individual postmenopausal woman, regression equations may be used to relate
      the data to 4CHW.

PMID- 17508097
TI  - Muscle phosphocreatine post-exercise recovery rate is related to functional
      evaluation in hospitalized and community-living older people.
AB  - OBJECTIVE: to explore muscle mitochondria function with respect to age,
      functional status and nutrition in community-living and recovering hospitalized
      older subjects. MEASUREMENTS: subjects were assessed for nutrition, hand-grip
      strength, 10-meter gait time, a modified timed get-up-and-go test and activities
      of daily living score (ADL). 31P magnetic resonance spectroscopy (31P MRS) was
      used to assess the initial rate of post-exercise phosphocreatine recovery (ViPCr)
      for mitochondrial function evaluation in 25 hospitalized older subjects (86.1 +
      5.3 y) and in 25 community-living younger ones (74.5 + 6.2 y). RESULTS: in
      multiple linear regression, longer time on the get-up-and-go test was
      independently associated with lower values of ViPCr (p = 0.008). For all subjects
      and in the 8 patients unable to perform this test, ViPCr was negatively
      correlated with the ADL score (respectively p < 0.001 and p = 0.025). CONCLUSION:
      particularly in hospitalized and frail older subjects, muscle mitochondrial
      function was related to the global physical functional assessment.

PMID- 17508098
TI  - Muscle power of lower extremities in relation to functional ability and
      nutritional status in very elderly people.
AB  - The purpose of this study was to explore the relationship between leg power and
      functional and nutritional status in very elderly people. A cross sectional
      analysis was conducted. Participants were men and women (n = 30, age: 82 +/- 5,3
      years). Leg extension maximal power was measured. Physical performance measures
      included chair rise time, time to walk 6 meters, and steps number (SN) necessary
      to cover a 6 meters walk at habitual gait speed. Nutritional status measurement
      included Mini Nutritional Assessment (MNA), Body Mass Index (BMI), calf
      circumference, and thigh volume. Leg extension power was significantly correlated
      with all the performance measures: chair rise time (r= - 0.57, p < 0.01), time to
      walk six meters (r = - 0.56, p < 0.01), number of steps to cover a six meters
      walk (r = - 0.46, p < 0.01). A curvilinear association was found between SN and
      maximal power (r2 = 0.43, p < 0.001). Maximal power and thigh volume explained
      significantly time to walk 6 meters in a non-linear regression analysis (r2 =
      0.82, p < 0.001). In conclusion, a low level of muscle power is associated with
      poor functional performances. Both weak muscle power and thigh volume are
      predictive of poor functional status. Because a decline in functional
      performances is highly predictive of subsequent disability and adverse events as
      falls, future studies should evaluate the effects of specific training designed
      to improve muscle power on disability and falls prevention.

PMID- 17508099
TI  - Antioxidant intake and cognitive function of elderly men and women: the Cache
      County Study.
AB  - OBJECTIVE: We prospectively examined associations between intakes of antioxidants
      (vitamins C, vitamin E, and carotene) and cognitive function and decline among
      elderly men and women of the Cache County Study on Memory and Aging in Utah.
      PARTICIPANTS AND DESIGN: In 1995, 3831 residents 65 years of age or older
      completed a baseline survey that included a food frequency questionnaire and
      cognitive assessment. Cognitive function was assessed using an adapted version of
      the Modified Mini-Mental State examination (3MS) at baseline and at three
      subsequent follow-up interviews spanning approximately 7 years. Multivariable
      mixed models were used to estimate antioxidant nutrient effects on average 3MS
      score over time. RESULTS: Increasing quartiles of vitamin C intake alone and
      combined with vitamin E were associated with higher baseline average 3MS scores
      (p-trend = 0.013 and 0.02 respectively); this association appeared stronger for
      food sources compared to supplement or food and supplement sources combined.
      Study participants with lower levels of intake of vitamin C, vitamin E and
      carotene had a greater acceleration of the rate of 3MS decline over time compared
      to those with higher levels of intake. CONCLUSION: High antioxidant intake from
      food and supplement sources of vitamin C, vitamin E, and carotene may delay
      cognitive decline in the elderly.

PMID- 17508100
TI  - Glycemic load and risk of Alzheimer's disease.
AB  - OBJECTIVE: to explore the relation of glycemic load (GL) with Alzheimer's disease
      (AD) risk. DESIGN: Cohort study. SETTING: Cohort of elderly subjects in New York
      City. PARTICIPANTS: 939 persons 65 years and older without dementia followed for
      an average of 6.3 years. MEASUREMENTS: Glycemic index, carbohydrate and calorie
      intake were measured using a semi-quantitative food frequency questionnaire
      (SFFQ). GL was calculated as the product of carbohydrate intake and glycemic
      index and adjusted for energy intake. AD was ascertained with standard research
      criteria. RESULTS: Cox regression was used to relate GL quartiles to AD using
      time from SFFQ to AD as the time-to-event variable. There was no association
      between GL and AD after adjustment for age, gender, education, ethnic group, and
      presence of diabetes. There was no evidence of modification by age, gender, APOE
      e4, and presence of diabetes. The only dietary variable associated with a higher
      risk of AD was total calories (HR of AD for a one-log unit increase =2.2; 95% CI:
      1.4,3.5) after adjustment for age, gender, ethnic group, education, diabetes, and
      APOE-e4. CONCLUSION: GL is not associated with a higher risk of AD in the
      elderly. Our data does not support the popular practice of low carbohydrate diets
      for the prevention of AD in the elderly.

PMID- 17508101
TI  - The effects of an intensive lifestyle modification program on sleep and stress
      disorders.
AB  - BACKGROUND: To determine if a lifestyle change program can modify behavior to
      reduce sleep and stress disorders. METHODS: Analyses are based on 2,624
      individuals aged 30 to 80 years from the Rockford, Illinois metropolitan area who
      completed a lifestyle evaluation at baseline and again after four weeks,
      following participation in a 40-hour educational course given over a four-week
      period. Participants receive instruction on the importance of making better
      lifestyle choices related to making long-term improvements in nutrition and
      physical activity and they learn ways to improve sleep and reduce stress in their
      lives. RESULTS: Significant percent decreases were observed in the number
      experiencing selected sleep or stress disorders from baseline to four weeks later
      for "sleeps restlessly" (-59%), "suffers from insomnia" (-64%), "feels under
      pressure" (-37%), "easily emotionally upset" (-52%), and "feels fearful or
      depressed" (-61%). Experiencing a selected sleep or stress disorder after four
      weeks among those who had the disorder at baseline was significantly more likely
      in those not physically active and/or not having lowered their BMI after four
      weeks. Changes in alcohol consumption and smoking did not significantly
      contribute to changes in the disorders. Those who failed to lower their
      coffee/tea use after four weeks were significantly more likely to have a sleep
      disorder and be easily emotionally upset. CONCLUSIONS: Changes in lifestyle
      behaviors after attending an educational program significantly reduced sleep and
      stress disorders in as little as four weeks, primarily explained by decreasing
      BMI and/or increasing exercise.

PMID- 17508102
TI  - Editorial: Geronto-Net : a network of exellence for clinical trials in
      geriatrics.

PMID- 17508103
TI  - GerontoNet: a network of excellence for clinical trials with geriatric patients.

PMID- 17508104
TI  - Methodological issues in geriatric research.
AB  - There are important differences between performing research in geriatric medicine
      and in other fields of medicine. Geriatric research requires specific
      preconditions in all phases of conducting research due to the heterogeneity among
      geriatric patients and the high prevalence of multi-morbidity, often resulting in
      impaired physical, psychological and social performances. This paper discusses
      issues important for successful recruitment and selection of subjects, the
      informed consent procedure and selection of appropriate research designs and
      research instruments in geriatric research. The recommendations given are based
      on a review of relevant literature and own research experiences in the 'Nijmegen
      geriatric research programme on Brain Failure'.

PMID- 17508105
TI  - Pharmacokinetics and drug toxicity in elderly patients: a case for geriatric core
      data in clinical trials.
AB  - The population in western countries is aging and elderly people are more likely
      to suffer diseases and receive treatments. Adverse reactions to drugs are more
      severe and frequent in the elderly patients, who are also less likely to report
      them. The present paper analyses the age induced changes in drug
      pharmacokinetics. For the purpose of improving the quality of clinical trials in
      geriatric patients and to set a network of clinical research centres, this paper
      proposes a series of 9 milestones. They are named geriatric core data and should
      be collected in each trial.

PMID- 17508106
TI  - Attrition in geriatric research: how important is it and how should it be dealt
      with?
AB  - Attrition, defined as a total loss to follow-up of participants, is a potential
      major bias in clinical trials. Participants can be lost for many reasons (death,
      illness, worsened health, refusal, withdrawal, lost to follow up). Attrition may
      be higher in older populations, so geriatric researchers should pay particular
      attention to the difficulties it raises. For a proper interpretation of research
      findings, a detailed analysis of the type of attrition observed and its possible
      determinants is essential, to determine if attrition has occurred at random or if
      it is associated to certain patient or treatment characteristics. This paper aims
      to review different causes of attrition, its prevalence among studies in
      different elderly populations, and its consequences on research findings. In
      addition, strategies used to minimise attrition (tracking, bonding, incentives)
      are discussed, and methods proposed to take this phenomenon into account are
      proposed.

PMID- 17508108
TI  - A minimum data set for intervention studies on cognitive decline (mild cognitive
      impairment, early Alzheimer) in the elderly.

PMID- 17508107
TI  - Rational for a minimum data set for clinical trials with geriatric patients.

PMID- 17508109
TI  - Minimum data set for research studies in falls and osteoporosis. Geronto Net.

PMID- 17508110
TI  - Towards a minimum data set for intervention studies in type 2 diabetes in older
      people.

PMID- 17508116
TI  - The definition and classification of dry eye disease: report of the Definition
      and Classification Subcommittee of the International Dry Eye WorkShop (2007).
AB  - The aim of the DEWS Definition and Classification Subcommittee was to provide a
      contemporary definition of dry eye disease, supported within a comprehensive
      classification framework. A new definition of dry eye was developed to reflect
      current understanding of the disease, and the committee recommended a three-part
      classification system. The first part is etiopathogenic and illustrates the
      multiple causes of dry eye. The second is mechanistic and shows how each cause of
      dry eye may act through a common pathway. It is stressed that any form of dry eye
      can interact with and exacerbate other forms of dry eye, as part of a vicious
      circle. Finally, a scheme is presented, based on the severity of the dry eye
      disease, which is expected to provide a rational basis for therapy. These
      guidelines are not intended to override the clinical assessment and judgment of
      an expert clinician in individual cases, but they should prove helpful in the
      conduct of clinical practice and research.

PMID- 17508117
TI  - The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of
      the International Dry Eye WorkShop (2007).
AB  - The report of the Epidemiology Subcommittee of the 2007 Dry Eye WorkShop
      summarizes current knowledge on the epidemiology of dry eye disease, providing
      prevalence and incidence data from various populations. It stresses the need to
      expand epidemiological studies to additional geographic regions, to incorporate
      multiple races and ethnicities in future studies, and to build a consensus on dry
      eye diagnostic criteria for epidemiological studies. Recommendations are made
      regarding several characteristics of dry eye questionnaires that might be
      suitable for use in epidemiological studies and randomized controlled clinical
      trials. Risk factors for dry eye and morbidity of the disease are identified, and
      the impact of dry eye disease on quality of life and visual function are
      outlined. Suggestions are made for further prospective research that would lead
      to improvement of both eye and general public health.

PMID- 17508118
TI  - Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic
      Methodology Subcommittee of the International Dry Eye WorkShop (2007).
AB  - The role of the Diagnostic Methodology Subcommittee of the Dry Eye Workshop was
      1) to identify tests used to screen, diagnose and monitor dry eye disease, 2) to
      establish criteria for test performance, and 3) to consider the utility of tests
      in a variety of clinical settings. The committee created a database of tests used
      to diagnose and monitor dry eye, each compiled by an expert in the field
      (rapporteur) and presented within a standard template. Development of the
      templates involved an iterative process between the Chairman of the subcommittee,
      the rapporteurs, and, at times, an additional group of expert reviewers. This
      process is ongoing. Each rapporteur was instructed on how to the complete a
      template, using a proforma template and an example of a completed template.
      Rapporteurs used the literature and other available sources as the basis for
      constructing their assigned template. The chairman of the subcommittee modifed
      the template to produce a standardized version and reviewed it with the
      rapporteur. The completed database will be searchable by an alphabetical list of
      test names, as well as by functional groupings, for instance, tests of aqueous
      dynamics, lipid functions, etc. The templates can be accessed on the website of
      the Tear Film and Ocular Surface Society (www.tearfilm.org). This report provides
      a general overview of the criteria applied in the development of tests for
      screening and diagnosis.

PMID- 17508119
TI  - Design and conduct of clinical trials: report of the Clinical Trials Subcommittee
      of the International Dry Eye WorkShop (2007).
AB  - This report summarizes some universal concepts with regard to clinical trials in
      general and other issues pertaining to clinical trials specifically tailored to
      the study of therapeutic intervention in dry eye disease. The report also makes
      recommendations for logistical design and implementation of such trials. It
      identifies peculiarities of dry eye disease that complicate clinical trial
      design, such as the lack of correlation of signs and symptoms, as well as the
      likelihood of control interventions having a lubricant (placebo) effect.
      Strategies for environmental trials and controlled adverse environment trials are
      reviewed.

PMID- 17508120
TI  - Management and therapy of dry eye disease: report of the Management and Therapy
      Subcommittee of the International Dry Eye WorkShop (2007).
AB  - The members of the Management and Therapy Subcommittee assessed current dry eye
      therapies. Each member wrote a succinct evidence-based review on an assigned
      aspect of the topic, and the final report was written after review by and with
      consensus of all subcommittee members and the entire Dry Eye WorkShop membership.
      In addition to its own review of the literature, the Subcommittee reviewed the
      Dry Eye Preferred Practice Patterns of the American Academy of Ophthalmology and
      the International Task Force (ITF) Delphi Panel on Dry Eye. The Subcommittee
      favored the approach taken by the ITF, whose recommended treatments were based on
      level of disease severity. the recommendations of the Subcommittee are based on a
      modification of the ITF severity grading scheme, and suggested treatments were
      chosen from a menu of therapies for which evidence of therapeutic effect had been
      presented.

PMID- 17508121
TI  - Research in dry eye: report of the Research Subcommittee of the International Dry
      Eye WorkShop (2007).
AB  - Members of the DEWS Research Subcommittee reviewed research into the basic
      mechanisms underlying dry eye disease. Evidence was evaluated concerning the tear
      film, lacrimal gland and accessory lacrimal glands, ocular surface epithelia
      (including cornea and conjunctiva), meibomian glands, lacrimal duct system and
      the immune system. Consideration was given to both animal and human research
      data. Results are presented as a series of information matrices, identifying what
      is known and providing supporting references. An attempt is made to identify
      areas for further investigation.

PMID- 17508124
TI  - Computed tomographic colonography: clinical value.
AB  - Computed tomographic colonography (CTC) has the potential to reliably detect
      polyps in the colon. Its clinical value is accepted for several indications. The
      main target is screening asymptomatic people for colorectal cancer (CRC). As in
      large multi-centre trials controversial results were obtained, acceptance of this
      indication on a large scale is still pending. Agreement exists that in
      experienced hands screening can be performed with CTC. This emphasizes the
      importance of adequate and intensive training. Besides this, other problems have
      to be solved. A low complication profile is mandatory. Perforation rate is very
      low. Ultra-low dose radiation should be used. When screening large patient
      cohorts, CTC will need a time-efficient and cost-effective management without too
      many false positives and additional exploration. Can therefore a cut-off size of
      polyp detection safely be installed? Is the flat lesion an issue? Can extra
      colonic findings be treated efficiently? A positive relationship with the gastro
      enterologists will improve the act of screening. Improvements of scanning
      technique and software with dose reduction, improved 3D visualisation methods and
      CAD are steps in the good direction. Finally, optimisation of laxative-free CTC
      could be invaluable in the development of CTC as a screening tool for CRC.

PMID- 17508125
TI  - Craniocervical instability in an infant with partial sacral agenesis.
AB  - Sacral agenesis is an uncommon condition characterised by total or partial
      absence of the sacrum. The association of this condition with craniocervical
      junction abnormalities is extremely rare. CASE REPORT: We describe a 3-year-old
      girl who, at the age of 8 months, while being investigated for short stature, was
      found to have significant craniocervical instability associated with anomalies of
      the odontoid peg. In addition to this she had partial sacral agenesis but genetic
      tests showed a normal karyotype. Due to the inherent difficulty of surgical
      fixation and immobilisation in an infant of her age, she was managed
      conservatively in a soft cervical orthosis. At the age of three years, surgery
      for decompression and stabilisation was deemed necessary due to the onset of
      neurological morbidity. CONCLUSION: The authors describe this extremely rare
      association and discuss the difficulties faced while deciding the optimum
      surgical strategy for managing such young children with craniocervical
      instability.

PMID- 17508127
TI  - Speciation process of Salvia isensis (Lamiaceae), a species endemic to serpentine
      areas in the Ise-Tokai district, Japan, from the viewpoint of the contradictory
      phylogenetic trees generated from chloroplast and nuclear DNA.
AB  - To understand the speciation process of Salvia isensis (Lamiaceae), a species
      endemic to a special environment (serpentine areas in the Ise-Tokai district,
      central Honshu, Japan), chloroplast DNA (cpDNA) and nuclear ribosomal DNA (nrDNA)
      were employed to analyze the phylogenetic relationships of S. isensis with
      related species in Japan. Allozymic polymorphisms were also used to analyze
      genetic relationships among Salvia species. A contradiction in the phylogenetic
      positions of species studied was detected when phylogenetic trees were
      constructed using cpDNA or nrDNA, i.e., S. isensis was a sister to the other
      species in phylogenetic trees generated from cpDNA, while S. japonica was a
      sister to the other species in the case of nrDNA. Genetic relationships between
      Salvia species estimated from allozymic polymorphisms did not contradict to the
      topology for nrDNA. Using the present results, the speciation process of S.
      isensis is discussed with regard to introgressive gene exchanges between related
      species.

PMID- 17508126
TI  - Reconsideration of an early dogma, saying "there is no evidence for disulfide
      bonds in proteins from archaea".
AB  - Stability and function of a large number of proteins are crucially dependent on
      the presence of disulfide bonds. Recent genome analysis has pointed out an
      important role of disulfide bonds for the structural stabilization of
      intracellular proteins from hyperthermophilic archaea and bacteria. These
      findings contradict the conventional view that disulfide bonds are rare in those
      proteins. A specific protein, known as protein disulfide oxidoreductase (PDO) is
      recognized as a potential key enzyme in intracellular disulfide-shuffling in
      hyperthermophiles. The structure of this protein consists of two combined
      thioredoxin-related units which together, in tandem-like manner, form a closed
      protein domain. Each of these units contains a distinct CXXC active site motif.
      Both sites seem to have different redox properties. A relation to eukaryotic
      protein disulfide isomerase is suggested by the observed structural and
      functional characteristics of the protein. Enzymological studies have revealed
      that both, the archaeal and bacterial forms of this protein show oxidative and
      reductive activity and are able to isomerize protein disulfides. The variety of
      active site disulfides found in PDO's from hyperthermophiles is puzzling. It is
      assumed, that PDO enzymes in hyperthermophilic archaea and bacteria may be part
      of a complex system involved in the maintenance of protein disulfide bonds.

PMID- 17508128
TI  - Archaic terms and dogmas impeding care of abdominal and pelvic herniation.
AB  - During the past 5000 years, ancient nomenclature and dogmas regarding the
      etiology of protrusions have accumulated. Whereas, in the abdomen, the Latin
      "hernia" supplanted Greek, it, based on content, persists in the pelvis as
      cystocele, rectocele, etc. Russell (Lancet 1:1519-1523, 1902) championed the
      congenital saccular theory of herniae, denying they could ever be acquired
      pathologically. Barring technical error, removal of the sac would cure. Despite
      dissent in the 1920s by Harrison, Keith, and Andrews, Russell's concepts held
      late into the twentieth century. We now know that pathology - systemic connective
      tissue disease - plays an important role in adult herniation. Tensionless
      prosthetic repair is usually required since the healing of damaged musculo
      aponeurotic structures in abdomen or pelvis is impaired. Laparoscopists have
      declared sliding extraperitoneal prolapse of sacless kidney, ureter, bladder, and
      fat pad to be herniae. Similar vaginal protrusions should be denoted likewise. It
      is time gynecologists and herniologists join in the effort to develop antidotes
      for combating this pernicious co-morbidity which has been shown also to cause
      aneurysms, diverticulosis coli, skin changes, and emphysema. Prophylaxis should
      include exercise and going without cigarettes.

PMID- 17508129
TI  - Graft failure: I. Endothelial cell loss.
AB  - Graft failure through endothelial cell loss is a constant threat throughout the
      lifetime of a corneal graft. It can occur at various time points after
      transplantation. Primary graft failure has nowadays become increasingly rare
      owing to meticulous eye banking methods and improved surgical techniques. Corneal
      graft rejection is always held responsible for endothelial cell loss. However a
      rejection episode that is promptly and adequately treated does not necessarily
      lead to a higher than expected cell loss. A more smouldering danger to ultimate
      graft survival is late endothelial failure. This gradual graft decompensation is
      secondary to a decrease in cell density below that necessary to maintain corneal
      deturgesence. The process of transplantation itself seems to set off a series of
      events (possibly immunological) that greatly exacerbates the endothelial cell
      loss compared to virgin corneas. This accelerated cell loss persists for at least
      10-15 years after transplantation, after which a more-stable situation is reached
      and cell attrition returns to normal rates. This provides a strong rationale for
      setting high donor standards of minimal cell density. Newer transplantation
      techniques such as deep anterior lamellar keratoplasty and deep lamellar
      endothelial keratoplasty could provide possible solutions to prevent this late
      endothelial failure. However they still have to prove themselves in the long run.

PMID- 17508130
TI  - AtCYT-INV1, a neutral invertase, is involved in osmotic stress-induced inhibition
      on lateral root growth in Arabidopsis.
AB  - Neutral/Alkaline invertases are unique to plant and photosynthetic bacteria. The
      function of Neutral/Alkaline invertases in plant development is not clear so far.
      In this study, we isolated an Arabidopsis (Col-0) mutant insensitive to osmotic
      stress-induced inhibition on lateral root growth. Map-based cloning reveals that
      a neutral invertase gene (AtCYT-INV1) was point-mutated. The mutant Atcyt-inv1
      showed short primary root, smaller size of leaves and siliques, and promotion of
      the reproductive compared to the wild type (WT). Carbohydrate measurement showed
      that sucrose is accumulated and glucose is reduced in the mutant Atcyt-inv1 under
      normal and 3% mannitol treatments. Taken together, AtCYT-INV1 plays multiple
      roles in plant development and is involved in osmotic stress-induced inhibition
      on lateral root growth by controlling the concentration of hexose in cells.

PMID- 17508131
TI  - Isolation of a novel complex of the SWI/SNF family from Schizosaccharomyces pombe
      and its effects on in vitro transcription in nucleosome arrays.
AB  - The family of ATP-dependent chromatin-remodeling factors plays a central role in
      eukaryotic transcriptional regulation. These complexes can alter the structure of
      chromatin by mechanisms that involve nucleosome sliding, dissociation, or
      replacement over a specific promoter. The SWI/SNF chromatin-remodeling complex is
      required for transcriptional activation or repression in a subset of genes. In
      the present study we have isolated the spSWI/SNF complex from Schizosaccharomyces
      pombe, which has at least seven subunits among them spSwi1-like and the catalytic
      subunit spBrg1. These subunits are homologues to Swi1 and Swi2/Snf2, respectively
      in Sacharomyces cerevisiae. Moreover, we have demonstrated that spSWI/SNF is able
      to promote in vitro transcription by RNA polymerase II (RNAPII) in a
      reconstituted system. In our transcription assays with cellular extracts of Sc.
      pombe we did not observe inhibition when alpha-Swi1 antibodies were utilized,
      indicating that other chromatin-remodeling complexes may allow transcription in
      Sc. pombe.

PMID- 17508133
TI  - Pheromone-based arrestment behavior in the common silverfish, Lepisma saccharina,
      and giant silverfish, Ctenolepisma longicaudata.
AB  - Aggregations of the common silverfish, Lepisma saccharina, and giant silverfish,
      Ctenolepisma longicaudata (both Thysanura: Lepismatidae), are mediated by species
      specific pheromones. In dual-choice, still-air olfactometer experiments, filter
      paper previously exposed to 12 male, female, or juvenile L. saccharina or C.
      longicaudata arrested conspecifics regardless of developmental stage or sex.
      Arrestment responses required physical contact with the pheromone. Insect-derived
      frass, scales, antennae, and setae, as well as salivary gland content, are not
      the source of the contact pheromone in L. saccharina. Lepisma saccharina did not
      respond to the pheromone of C. longicaudata, nor to that of another thysanuran,
      the firebrat Thermobia domestica. However, C. longicaudata responded to
      pheromones of both L. saccharina and T domestica, whereas T. domestica responded
      to the C. longicaudata but not L. saccharina pheromone. These results support the
      hypothesis that a closer phylogenetic relationship exists between C. longicaudata
      and T domestica than between C. longicaudata and L. saccharina, but a definitive
      conclusion must await molecular genetic analyses of all three species.

PMID- 17508132
TI  - Sol-gel-derived TiO(2)-SiO (2) implant coatings for direct tissue attachment.
      Part I: design, preparation and characterization.
AB  - A series of sol-gel derived TiO(2)-SiO(2) mixed oxide coatings were prepared by
      carefully controlling the process parameters to obtain silica-releasing coatings
      consisting of nanoparticles. These features are of paramount importance for
      enhanced cell adhesion and activation. To achieve both these goals the Ti
      alkoxide and Si-alkoxide were first separately hydrolysed and the titania-silica
      mixed sol was further reacted before the dipping process to obtain the desired
      particle sizes resulting to the biologically favourable topographical features.
      Silica release was observed from all the prepared coatings and it was dependent
      on SiO(2) amount added to the sols, i.e., the higher the added amount the higher
      the release. In addition, calcium phosphate was able to nucleate on the coatings.
      From the obtained SiO(2) dissolution data, together with the detailed XPS peak
      analysis, the mixed oxide coatings are concluded to be chemically heterogeneous,
      consisting of TiO(2) and SiO(2) species most likely linked together by Ti-O-Si
      bonds. TiO(2) is chemically stable making long-term implant coating possible and
      the desired nanoscale dimensions were well preserved although the composition was
      changed as a consequence of SiO(2) dissolution under in vitro conditions.

PMID- 17508134
TI  - The egg parasitoid Trissolcus basalis uses n-nonadecane, a cuticular hydrocarbon
      from its stink bug host Nezara viridula, to discriminate between female and male
      hosts.
AB  - Contact kairomones from adult southern green stink bugs, Nezara viridula (L.)
      (Heteroptera: Pentatomidae) that elicit foraging behavior of the egg parasitoid
      Trissolcus basalis (Wollaston) were investigated in laboratory experiments.
      Chemical residues from tarsi and scutella of N. viridula induced foraging by
      gravid female T. basalis. Residues from body parts of female N. viridula elicited
      stronger responses than those from the corresponding body parts of males.
      Deproteinized tarsi still elicited searching responses from wasps, indicating
      that the kairomone was not proteinaceous. Hexane extracts of host cuticular
      lipids induced searching responses from T. basalis, with a strong preference for
      extracts from female hosts. Extracts consisted primarily of linear alkanes from
      nC19 to nC34, with quantitative and qualitative differences between the sexes.
      Extracts of female N. viridula contained more nC23, nC24, and nC25 than the
      corresponding extracts from males, whereas nC19 was detected only in extracts
      from males. Direct-contact solid phase microextraction (DC-SPME) of N. viridula
      cuticle and of residues left by adult bugs walking on a glass plate confirmed
      gender-specific differences in nC19. Trissolcus basalis females responded weakly
      to a reconstructed blend of the straight-chain hydrocarbons, suggesting that
      minor components other than linear alkanes must be part of the kairomone.
      Addition of nC19 to hexane extracts of female N. viridula significantly reduced
      the wasps' arrestment responses, similar to wasps' responses to hexane extracts
      of male hosts. Overall, our results suggest that a contact kairomone that elicits
      foraging by T. basalis females is present in the cuticular lipids of N. viridula,
      and that the presence or absence of nC19 allows T. basalis females to distinguish
      between residues left by male or female hosts. The ecological significance of
      these results in the host location behavior of scelionid egg parasitoids is
      discussed.

PMID- 17508135
TI  - Psychosocial interventions in people with multiple sclerosis: a review.
AB  - BACKGROUND: Upon diagnosis individuals with Multiple Sclerosis (MS) must cope
      with both day to day and disease-related stressors in addition to unpredictable,
      fluctuating and confusing symptoms. Furthermore, disease progression may
      interfere with employment, family life, relationships and social activities.
      Psychosocial interventions aim to help individuals manage these psychological,
      social and emotional challenges. However, there are no specific guidelines
      available regarding the most effective intervention content, format or delivery.
      Therefore, a review of the research that has utilised these interventions,
      specifically those which, by definition, aimed to improve quality of life (QoL)
      and/or well-being in people with MS, was considered essential in order to
      identify which aspects of these interventions may help alleviate the psychosocial
      challenges associated with MS. OBJECTIVES: To identify all randomised controlled
      trials (RCTs), quasi-experimental, cohort, case control and case series studies
      that have investigated psychosocial interventions in people with MS which aimed
      to improve QoL and/or well-being, to establish the methodological quality of such
      studies, and to determine the effectiveness of the interventions. SEARCH
      STRATEGY: Searches were carried out using computerised databases with predefined
      search terms; this was supplemented by manual searches of reference lists of all
      retrieved articles. Relevant journals were also hand searched. SELECTION
      CRITERIA: Studies written in English and published before January 2006,
      investigating the effectiveness of psychosocial interventions on QoL and/or well
      being in people with MS, were eligible for inclusion. DATA COLLECTION AND
      ANALYSIS: Methodological quality was independently assessed by two reviewers
      using the Downs and Black quality scoring checklist. The qualitative and
      quantitative characteristics of studies were extracted using a data extraction
      sheet. MAIN RESULTS: Thirty-three studies fulfilled the inclusion criteria;
      however, interventions varied widely in content, delivery and duration.
      Furthermore, failure to report full methodological details, as well as weaknesses
      in study design, reduced the strength of inferences that could be drawn from
      these studies. These notwithstanding, there were three studies of sufficient
      quality to provide some evidence regarding the value of education/information,
      goal setting, homework assignments, exercise, discussion forums and
      multidisciplinary team support. Thus, this review has identified the potential
      benefit of the aforementioned activities in the psychosocial management of this
      population. However, further well designed clinical trials are warranted to
      determine, definitively, the effectiveness, or otherwise, of these components.

PMID- 17508136
TI  - Cutaneous silent periods in the evaluation of cord compression in cervical
      spondylosis.
AB  - OBJECTIVE: The clinical diagnosis of cervical spondylotic myelopathy (CSM) may be
      challenging in patients with cervical spondylosis (CS). Routine nerve conduction
      studies (NCS) may not evaluate cord compression adequately. METHODS: We obtained
      cutaneous silent periods (CSP) in 26 consecutive patients presenting with
      clinical features of CS, in comparison with 30 normal controls. The results were
      also compared with transcranial magnetic stimulation (TMS) findings, and magnetic
      resonance imaging of the cervical cord as the gold standard. RESULTS: CSP
      findings showed similarly high sensitivity of up to 96% with TMS in evaluating
      cervical cord dysfunction. CONCLUSION: In specific clinical settings, CSP is of
      value for the diagnosis of CSM in CS. CSP measurement is advocated as a simple
      and rapid diagnostic adjunct to NCS in evaluating CS patients with possible cord
      compromise.

PMID- 17508137
TI  - Elevated intrathecal antibodies against the medium neurofilament subunit in
      multiple sclerosis.
AB  - Neurofilaments are cytoskeletal proteins localized within axons, which may
      interact with the immune system during and following tissue destruction in
      multiple sclerosis (MS). Antibodies against the medium neurofilament subunit
      synthesized intrathecally may reflect axonal damage in MS patients. Both
      immunoglobulin G (IgG) and M (IgM) responses against the purified native medium
      subunit of neurofilaments (NFM) using enzyme-linked immunosorbent assay (ELISA)
      were determined in paired serum and cerebrospinal fluid samples obtained from 49
      MS patients, 16 normal controls (CN), 21 control patients with miscellaneous
      diseases (CD) and 14 patients with neurodegenerative disorders (CDEG).
      Intrathecal production of IgM and IgG antibodies to NFM were elevated in MS
      patients compared with the CN or CD groups (p<0.04 for IgM, p<0.01 for IgG). The
      increase was present in all the MS courses (relapsing-remitting, primary and
      secondary progressive). Similar local anti-NFM IgG and IgM synthesis occurred in
      the MS and CDEG groups. MS patients with short and long disease duration did not
      differ in terms of their anti-NFM IgM and IgG responses. Repeated examinations
      showed stable intrathecal anti-NFM production. Intrathecal IgG and IgM antibodies
      against NFM were increased in MS patients and may serve as a potential marker for
      axonal pathology. The extent of anti-NFM levels did not correspond to any
      individualized clinical profiles of MS patients.

PMID- 17508138
TI  - The effect of age of onset of PD on risk of dementia.
AB  - BACKGROUND: Dementia occurs in the majority of patients with Parkinson's disease
      (PD). Late onset of PD has been reported to be associated with a higher risk for
      dementia. However, age at onset (AAO) and age at baseline assessment are often
      correlated. The aim of this study was to explore whether AAO of PD symptoms is a
      risk factor for dementia independent of the general effect of age. METHODS: Two
      community-based studies of PD in New York (n=281) and Rogaland county, Norway
      (n=227) and two population-based groups of healthy elderly from New York (n=180)
      and Odense, Denmark (n=2414) were followed prospectively for 3-4 years and
      assessed for dementia according to DSM-IIIR. All PD and control cases underwent
      neurological examination and were followed with neurological and
      neuropsychological assessments. We used Cox proportional hazards regression based
      on three different time scales to explore the effect of AAO of PD on risk of
      dementia, adjusting for age at baseline and other demographic and clinical
      variables. FINDINGS: In both PD groups and in the pooled analyses, there was a
      significant effect of age at baseline assessment on the time to develop dementia,
      but there was no effect of AAO independent of age itself. Consistent with these
      results, there was no increased relative effect of age on the time to develop
      dementia in PD cases compared with controls. INTERPRETATION: This study shows
      that it is the general effect of age, rather than AAO that is associated with
      incident dementia in subjects with PD.

PMID- 17508139
TI  - Subclinical diabetic neuropathy with normal conventional electrophysiological
      study.
AB  - BACKGROUND: For early detection and prevention of diabetic neuropathy, it is
      important to identify subclinical diabetic neuropathy. Routine nerve conduction
      study often fails to detect early stage of neuropathy. OBJECTIVES: The purpose of
      this study is to evaluate the clinical usefulness of electrophysiological indexes
      in detecting early diabetic neuropathy with no objective clinical or
      electrophysiological abnormalities. MATERIALS AND METHODS: Nerve conduction study
      of upper/lower limbs was investigated in 31 subclinical diabetic neuropathy
      patients with normal nerve conduction studies(group I), 38 clinical diabetic
      neuropathy patients with normal nerve conduction studies(group II) and 31 normal
      controls. Residual latency (RL), terminal latency index (TLI) and modified F
      ratio (MFR) were calculated and compared among groups. RESULTS: Compared with
      controls, MFR of lower limbs and TLI of both upper/lower limbs were significantly
      decreased in both group I and II (p<0.05). RL was increased in both groups, but
      the difference was not statistically significant. Comparing the indexes between
      group I and II, there was no significant difference. CONCLUSIONS: RL, TLI and
      MFR, which reflect distal conduction slowing, may be useful indexes to identify
      subclinical diabetic neuropathy. The results also suggest that
      electrophysiological changes that are obscured in routine nerve conduction study
      are present before the clinical manifestation.

PMID- 17508140
TI  - Visual attention in patients with intracranial arachnoid cysts.
AB  - OBJECTIVE: To investigate whether intracranial arachnoid cysts (AC) compromise
      visual attention and if so, whether surgical cyst decompression leads to
      improvement in visual attention performance. METHODS: The experiments were
      carried out on 27 patients with temporal (n=21) or frontal (n=6) AC, and 27
      healthy control subjects. All subjects were tested with two different visual
      attention paradigms. Patients were tested one day before and a minimum of 3
      months after the surgery, with the same test-retest interval for the controls.
      RESULTS: AC impair both automatic and effortful attention. These attention
      impairments were significantly improved after surgery, also when controlling for
      learning and practice effects from pre- to post-surgery testing. Closer analysis
      showed that these effects were carried by patients with right hemisphere cysts
      for impairment in shift of attention, and by patients with a left hemisphere cyst
      for visual search. CONCLUSIONS: AC may impair visual attention. Cyst location may
      be of importance for the development of these attention deficits, as there were
      significant differences between patients with right hemisphere cysts and those
      with left hemisphere cysts. This dyscognition appears to be reversible following
      surgical decompression. Surgical decompression of AC may thus relieve not only
      clinical symptoms and complaints, but cognitive impairments as well.

PMID- 17508141
TI  - A brain magnetization transfer MRI study with a clinical follow up of about four
      years in patients with clinically isolated syndromes suggestive of multiple
      sclerosis.
AB  - Whereas it is important to gain prognostic information in patients with
      clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS), there
      is still a lack of definitive data about the significance of normal-appearing
      white (NAWM) and gray (NAGM) matter damage in these patients. The aim of this
      study was to clarify the role of magnetization transfer magnetic resonance
      imaging (MT MRI) in assessing "occult" damage at the earliest clinical stage of
      MS. Dual echo, post-contrast T1-weighted, and MT MRI were obtained from 43 CIS
      patients with paraclinical evidence of spatial disease dissemination within 3
      months from disease onset and from 22 controls. In patients, conventional MRI was
      obtained after 3 and 12 months from the baseline assessment, to detect disease
      dissemination in time (DIT). A neurological examination was also conducted to
      ascertain the occurrence of relapses for an average follow up period of 1389
      (range = 420-1847) days. MTR maps were derived and NAWM and NAGM MT ratio (MTR)
      histograms were analyzed. During the follow up, 30 patients showed MRI evidence
      of DIT, and 21 experienced a relapse. T2 lesion volume (LV) was significantly
      higher in patients with DIT than in those without (p=0.005). MTR histogram
      variables did not significantly differ between patients with MRI or clinical DIT.
      T2 LV was the only significant predictor of clinical DIT at follow-up (p=0.001).
      This study shows that MT MRI-detectable damage to NAWM and NAGM may not be an
      important feature of all patients at presentation with a CIS highly suggestive of
      MS and that such a damage may develop with subsequent disease evolution.

PMID- 17508142
TI  - Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson's
      disease.
AB  - Olfactory dysfunction is a frequent and early feature of Parkinson's disease
      (PD), often preceding the motor symptoms by several years. Assessment of
      olfactory deficits may be used in the diagnostic assessment of PD. In this study
      we investigated the relationship between selective deficits in smell
      identification and nigrostriatal dopaminergic denervation in patients with PD.
      Twenty-seven PD patients (Hoehn and Yahr stages I-III) and 27 healthy controls
      matched for gender and age underwent olfactory testing using the 40-odor
      University of Pennsylvania Smell Identification Test (UPSIT). PD patients
      underwent (11)C-beta-CFT dopamine transporter (DAT) positron emission tomography
      (PET) imaging and clinical motor examination. We found that total UPSIT scores
      were significantly lower in the PD than in the control subjects (z=4.7,
      p<0.0001). Analysis of the individual smell scores identified 3 odors with an
      accuracy of >0.75 for the diagnosis of PD. These odors were banana, licorice, and
      dill pickle. A PD-specific smell identification score (UPSIT-3) was calculated
      for these 3 odors. Analysis of the patient PET data demonstrated significant
      correlations between dorsal striatal DAT activity and the UPSIT-3 (R(S)=0.53,
      p=0.0027) and total UPSIT (R(S)=0.44, p=0.023) scores. UPSIT-3 (R(S)=0.43,
      p=0.027) but not total UPSIT (R(S)=0.20, ns) correlated with nigral DAT activity.
      We conclude that patients with PD have selective hyposmia. A simplified UPSIT
      smell identification test consisting of 3 PD-selective odors had more robust
      correlation with nigral and dorsal striatial dopaminergic activity compared with
      the full UPSIT scores in patients with PD. Assessment of selective olfactory
      deficits may be used as a simplified olfactory screening test in the evaluation
      of subjects with possible PD.

PMID- 17508143
TI  - Measuring cognitive change in older adults: reliable change indices for the
      SIDAM.
AB  - BACKGROUND: In clinical settings, neuropsychological tests and screening
      instruments are often used to measure cognitive change over time. However, the
      interpretation of changes in test scores is often difficult. For most instruments
      there is no information how much change occurs normally in cognitively healthy
      individuals. AIM: To examine what is a reliable change for a widely used
      screening instrument for cognitive impairment and dementia. METHODS: A Sample of
      119 cognitively normal elderly individuals aged 75 and over participated in the
      Leipzig Longitudinal Study of the Aged (LEILA 75+). All participants have been
      tested six times at 1.5 year intervals with the test part of the SIDAM over a
      mean period of 7.1 years. Reliable change indices (RCI) were computed for a
      common confidence interval (90%). It is demonstrated how to compute RCI for
      individual patients. RESULTS: In repeated assessments with 1.5 year intervals, a
      change in SIDAM score of at least 4 to 7 points (dependent on which of the six
      assessments were compared) indicates a reliable change at the 90% confidence
      level. Smaller changes can be interpreted only with high uncertainty. CONCLUSION:
      The interpretation of changes in test scores in older adults should account for
      potential practice effect, normal decline and regression to the mean.

PMID- 17508145
TI  - Movement disorder due to aceruloplasminemia and incorrect diagnosis of hereditary
      hemochromatosis.

PMID- 17508144
TI  - Bilateral subthalamic nucleus stimulation in advanced Parkinson's disease: three
      years follow-up.
AB  - OBJECTIVE: To assess the long-term efficacy and safety of chronic bilateral
      stimulation of the subthalamic nucleus (STN) in patients with advanced
      Parkinson's disease (PD). METHODS: 36 consecutive patients with idiopathic
      Parkinson's disease treated with bilateral stimulation of the STN were studied.
      Parkinsonian status was assessed preoperatively and at 1 and 3 years
      postoperatively using the Unified Parkinson's Disease Rating Scale (UPDRS) and
      neuropsychological evaluation in on and off-medication / on and off stimulation
      conditions. RESULTS: At 3 years follow-up, STN stimulation reduced the UPDRS
      motor score by 54.2 % compared to baseline in the off-medication conditions.
      Tremor, rigidity, bradykinesia, postural stability, and gait improved by 72.2 %,
      62.4 %, 56.8 %, 40.5 % and 45.3 %, respectively. UPDRS part II scores were
      reduced by 41.4 %. The overall dopaminergic drugs dose was reduced by 48.6 %
      after surgery and four patients were no longer taking antiparkinsonian medication
      at three years. However, axial dopa-unresponsive signs worsened in some patients.
      The most frequent transient adverse event consisted in mood disorders in 23
      patients. CONCLUSIONS: Our data demonstrate that: 1) bilateral STN stimulation is
      relatively safe, improves the motor symptoms and drug-related motor complications
      of PD, and reduces the daily dosage of medication; 2) this benefit is sustained
      over time despite the occurrence of axial doparesistant signs in some patients.

PMID- 17508146
TI  - Interaction between prion protein and interleukin-1A genes increases early-onset
      Alzheimer's disease risk.

PMID- 17508147
TI  - Can an ordinary neurological examination induce a dissection of the vertebral
      artery?: a case report.

PMID- 17508148
TI  - Upbeat nystagmus due to a caudal medullary lesion and influenced by gravity.

PMID- 17508149
TI  - Christfried Jakob (1866-1956).

PMID- 17508154
TI  - Neuroimaging: visualising the brain in pain.
AB  - The neuroimaging of experimental and clinical pain has revolutionised our
      understanding of the physiological responses to pain and paved the way for a
      better understanding of the pathophysiology of chronic pain syndromes. Extensive
      research on the central mechanisms regarding the sensory-discriminative
      dimensions of pain have revealed a complex network of cortical and subcortical
      brain structures involved in the transmission and integration of pain, the so
      called pain matrix. Although brain imaging and pharmacological studies have
      generated some insight into the circuitry that may be involved in the generation
      of chronic pain symptoms, further research into brain imaging of chronic pain is
      clearly warranted. However, modern neuroimaging suggests that the chronification
      of pain (and headaches) involves functional and structural plasticity of both the
      central and peripheral nervous system.

PMID- 17508156
TI  - The role of the clinician in interpreting conventional neuroimaging findings in
      migraine patients.
AB  - Changes in cerebral white matter at CT or MRI have been reported in patients with
      migraine, especially in those with migraine with aura. Similar pictures may be
      present in asymptomatic subjects, and their nature is not completely understood,
      but their infarct-like nature is strongly suggested. Clinicians play an important
      role in the evaluation of those migraine patients in whom these nonspecific
      abnormalities are present. We suggest ruling out specific syndromes in which
      migraine attacks are associated with white matter changes (CADASIL, MELAS,
      multiple sclerosis and central nervous system vasculitis), as well as evaluating
      the presence of different vascular risk factors (genetic prothrombotic factors,
      patent foramen ovale, use of oral contraceptives, etc.). Their possible causative
      role in MRI lesions and in enhancing the risk of a negative clinical evolution
      must be considered in each individual case.

PMID- 17508155
TI  - Functional neuroimaging and headache pathophysiology: new findings and new
      prospects.
AB  - In the last ten years pathophysiology of primary headaches has received new
      insights from neuroimaging studies. Positron emission tomography (PET) showed
      activation of specific brain structures, brainstem in migraine and hypothalamic
      grey in trigeminal autonomic cephalalgias. This brain activation suggests it may
      intervene both in a permissive or triggering manner and as a response to pain
      driven by the first division of the trigeminal nerve. Voxel-based morphometry has
      suggested that there is a correlation between the brain area activated
      specifically in acute cluster headache - the posterior hypothalamic grey matter -
      and an increase in grey matter in the same region. New insights into mechanisms
      of head pain have emerged thanks to neuroimaging obtained in experimentally
      induced headaches, and during peripheral and central neurostimulation.

PMID- 17508157
TI  - The patent foramen ovale-migraine question.
AB  - A strong association between migraine with aura and patent foramen ovale (PFO)
      with shunting has been suggested. Similarly, an association of migraine with aura
      and Osler-Weber-Rendu disease, probably also due to shunting though pulmonary
      arteriovenous malformations has been proposed. PFOs are also comorbid with
      cryptogenic strokes, refractory hypoxaemia in right ventricular infarction or
      severe lung disease, orthostatic oxygen desaturation and decompression illness in
      scuba divers.Multiple open-label, retrospective and case-controlled studies of
      PFO closure report improvement of migraine with aura. MIST, the only prospective
      sham-controlled study of PFO closure for migraine with aura, did not reach its
      primary endpoint for migraine resolution, although it clearly demonstrated an
      association between migraine with aura and the severity of the PFO shunt. One
      reported secondary endpoint showed a significant 42% reduction of migraine days,
      suggesting the need for further randomised, sham-controlled PFO closure studies.

PMID- 17508158
TI  - Can behavioural therapy influence neuromodulation?
AB  - This paper reviews non-invasive behavioural approaches - broadly construed as
      cognitive, affective, behavioural and psychophysiological interventions - and
      examines whether they can impact central, peripheral or autonomic nervous system
      components responsive to pain in general and headache in particular. It focuses
      on two developing bodies of literature - neurophysiology of migraine and fMRI
      studies of pain networks. The available literature suggests behavioural
      interventions can affect neuromodulation, although further research is clearly
      warranted.

PMID- 17508159
TI  - The patient-physician relationship in the approach to therapeutic management.
AB  - Recent epidemiological investigations have demonstrated that migraine, and more
      generally primary headaches, are underdiagnosed and poorly treated. To tackle and
      resolve this problem, in addition to identifying efficient screening means and
      reliable disability measurement tools, it is crucial to improve communication
      between physicians and patients. In particular, physicians should be willing and
      have time to establish a relationship of active and mutual cooperation with their
      patients and should do so through a number of inescapable steps: listening to
      patients, understanding their needs, identifying with their condition, giving
      them explanations and information, reassuring their concerns, advising them on
      what should be done, making sure that they have correctly understood what they
      have been told, finding out whether they want to be involved in decision-making
      and choosing a treatment. Patients must be in a position to freely express their
      opinions, with no hurry and without fear. Indeed, the time spent with patients,
      as Graham pointed out as early as 40 years ago, is the most important ingredient
      of migraine therapy. Proper measures should be taken to overcome the two major
      obstacles that stand in the way of a good patient-physician relationship: a
      physician's lack of adequate skills and the organisational absurdities of the
      health system.

PMID- 17508160
TI  - Chronic headaches: pharmacological and non-pharmacological treatment.
AB  - Chronic headaches have increasingly become a focus within the field of head pain.
      Most patients with frequent headache eventually overuse their medications, and
      when it happens, the diagnosis of medication-overuse headache is clinically
      important, because patients rarely respond to preventive medications whilst
      overusing acute medications. Properly treating medication overuse and preventing
      relapse require recognition of the different factors that contribute to its
      development and perpetuation, including some behaviours and psychological
      elements that are important in sustaining the overuse of medication. The
      different therapeutical approaches, pharmacological and nonpharmacological,
      initial outcomes and long-term durability of treatment are discussed.

PMID- 17508162
TI  - Deep brain stimulation in craniofacial pain: seven years' experience.
AB  - Cluster headache (CH) is a primary headache with excruciatingly painful attacks
      that are strictly unilateral. About 10% of cases experience no significant
      remission, and about 15% of these do not respond to medication, so surgery is
      considered. Neuroimaging studies show that the posterior inferior hypothalamus is
      activated during CH attacks and is plausibly the CH generator. We report on 16
      chronic CH patients, with headaches refractory to all medication, who received
      long-term hypothalamic stimulation following electrode implant to the posterior
      inferior hypothalamus. After a mean follow-up of 23 months, a persistent pain
      free to almost pain-free state was achieved in 13/16 patients (15/18 implants;
      83.3%) a mean of 42 days (range 1-86 days) after monopolar stimulation
      initiation. Ten patients (11 implants) are completely pain-free. A common side
      effect was transient diplopia, which limited stimulation amplitude. In one
      patient, a small non-symptomatic haemorrhage into the 3rd ventricle occurred
      following implant, but regressed 24 h later. Persistent side effects are absent
      except in one patient with bilateral stimulation, in whom stimulation was stopped
      to resolve vertigo and worsened bradycardia, but was resumed later without
      further problems. Hypothalamic stimulation is an effective, safe and well
      tolerated treatment for chronic drug-refractory CH. It appears as a valid
      alternative to destructive surgical modalities, and has the additional advantage
      of being reversible.

PMID- 17508161
TI  - Update on neurosurgical treatment of chronic trigeminal autonomic cephalalgias
      and atypical facial pain with deep brain stimulation of posterior hypothalamus:
      results and comments.
AB  - The objective of this study is to describe the therapeutic effect and the
      technical and surgical problems of deep brain stimulation (DBS) of the posterior
      hypothalamus over seven years, for treatment of chronic trigeminal autonomic
      cephalalgias and atypical facial pain. We report a surgical series of 20 patients
      that underwent DBS of the posterior hypothalamus. This series includes 16
      patients with chronic cluster headache (CH), one patient with short-lasting
      unilateral neuralgiform headache attacks with conjunctival injection and tearing
      (SUNCT) and three patients with atypical facial pain. All patients of this series
      were resistant to any pharmacological and conservative treatment. The stimulated
      target was the same in the whole series even though stereotactic coordinates of
      the target referred to the midcommissural point differ slight in the Y
      anteroposterior value due to individual anatomical variability. The commissures
      based reference system was adapted to individual anatomical landmarks of the
      brainstem adding to the registration a third reference point below the
      commissural plane. The stimulation parameters of unipolar stimulation were
      similar in the whole series: 180 Hz, 60 mus, 1-3 V. In the CH series, at five
      years follow-up the percentage of total number of days free from pain attacks
      improved from 1%-2% to 71%. Ten patients of this series had a complete and
      persistent pain-free state at 18 months follow-up and the patient with SUNCT has
      complete pain relief. In the three patients with atypical facial pain, the
      neurostimulation procedure was absolutely unsuccessful. DBS of the posterior
      hypothalamus produced a significant and marked reduction of pain bouts in CH
      patients and in the SUNCT patient. The attempts to treat atypical facial pain in
      three patients failed.

PMID- 17508163
TI  - Migraine and epilepsy: clinical and pathophysiological relations.
AB  - Migraine and epilepsy are both chronic disorders characterised by recurrent
      neurological attacks, with a partial clinical and therapeutic overlap and
      frequently occurring together. Although still incompletely clarified, the
      possible existence of a link between migraine and epilepsy has long been debated.
      In this paper the epidemiologic evidence of migraine and epilepsy comorbidity,
      the possible occurrence of both disturbances in close temporal association,
      possible shared physiopathologic mechanisms and the rationale for antiepileptic
      drug use in migraine prophylaxis will be discussed.

PMID- 17508164
TI  - Migraine and cerebrovascular disease.
AB  - The association between migraine and stroke is complex and bidirectional.
      Epidemiological studies suggest that migraine may be a risk factor for stroke;
      magnetic resonance studies suggest that white matter abnormalities may be more
      frequent in migraine patients than in controls; and stroke may occur during the
      course of a migraine with aura (MA) attack (migrainous stroke). However, the
      relationship between migraine, aura and stroke is complex and mechanisms other
      than a direct cause/effect relationship are possible. Migraine aura may be the
      consequence, rather than the cause of cerebral ischaemia. Furthermore both MA and
      stroke may be secondary to a third underlying condition. In this review we
      analyse data regarding the relationship between migraine and stroke considering 3
      aspects: (1) migraine as a risk factor for stroke, (2) migraine as a cause of
      stroke and (3) migraine and cerebral ischaemia sharing a common cause.

PMID- 17508165
TI  - Migraine and depression.
AB  - Investigations of migraine comorbidity have confirmed its association with
      diverse psychiatric conditions. This association appears to be stronger for major
      depression and anxiety disorders, but comorbidity has also been reported with
      substance abuse and certain mood disorders. This literature also indicates that
      greater psychiatric comorbidity exists for migraine sufferers with aura than
      without. There is evidence that psychiatric comorbidity is higher in transformed
      migraine than in episodic migraine. However, research into the possible
      mechanisms underlying these associations remains limited. Subjects with migraine
      should be carefully screened for depression, which should be managed to prevent
      transformation of migraine, to increase quality of life and to gain more
      successful migraine therapies.

PMID- 17508166
TI  - The future of acute care and prevention in headache.
AB  - Migraine is a chronic neurological disease with heterogeneous characteristics
      resulting in a range of symptom profiles, burden and disability. It affects
      nearly 12% of the adult population in Western countries and up to 22% of the
      Brazilian population, imposing considerable suffering as well as personal,
      economic and social losses. The pharmacological treatment of migraine is divided
      into preventive and acute treatment. A better comprehension of migraine
      pathophysiology, as well as the finding of novel molecular targets, has led to a
      growing number of upcoming therapeutic opportunities. The same is true of cluster
      headache, which affects only about 0.07%-0.4% of most populations. This review
      focuses on current and emerging agents and procedures for the treatment of
      migraine and cluster headache.

PMID- 17508167
TI  - Caffeine and headaches.
AB  - Caffeine is the most widely consumed psychostimulant drug. It is a potent
      antagonist of adenosine receptors at dosages consistent with common dietary
      intake. With infrequent exposure, caffeine may act as an analgesic for headache
      or an adjuvant for the actions of other analgesics. With chronic repetitive
      intake, caffeine is associated with an increased risk of development of
      analgesicoveruse headache, chronic daily headache and physical dependency.
      Cessation of caffeine use following chronic exposures leads to a withdrawal
      syndrome, with headache as a dominant symptom.

PMID- 17508168
TI  - Is migraine a risk factor in pregnancy?
AB  - Most epidemiological studies demonstrate that women suffering from migraine note
      significant improvement of their headaches during pregnancy. It is generally
      supposed, by both headache specialists and gynaecologists, that migraine does not
      involve any risk to the mother or the foetus. Specific investigations of the
      medical complications of pregnancy in migrainous women, however, have recently
      cast doubt on this assumption. Most studies, indeed, have revealed a significant
      association between migraine and hypertension in pregnancy (i. e., preeclampsia
      and gestational hypertension). Migraine has also been recently postulated as one
      of the major risk factors for stroke during pregnancy and the puerperium. There
      is thus an urgent need for prospective studies of large numbers of pregnant women
      to determine the real existence and extent of the risks posed by migraine during
      pregnancy.

PMID- 17508169
TI  - Antiepileptic drugs in the prophylaxis of migraine, chronic headache forms and
      cluster headache: a review of their efficacy and tolerability.
AB  - The studies of different antiepileptic drugs (AEDs) in the prophylaxis of
      episodic migraine, cluster headache (CH) and chronic headache forms (chronic
      daily headache, transformed or chronic migraine, chronic tension-type headache)
      are reviewed. The main results from published trials are summarised - focusing on
      responder rates as reported in placebo-controlled, double-blind studies. Most
      common adverse events are also discussed. This review indicated that robust
      evidence supports the use of sodium valproate-divalproex and of topiramate (TPM)
      in the prophylaxis of migraine, while definitive conclusions about the real
      effects of other AEDs in migraine cannot be drawn. Overall, evidence of efficacy
      of different AEDs in chronic headache forms and in CH is still lacking, most
      studies being open-label, small-sample trials. Nevertheless, encouraging data
      from controlled trials are emerging for TPM in the treatment of chronic headache
      forms.

PMID- 17508170
TI  - Hypothalamus and headaches.
AB  - The hypothalamus forms part of the central autonomic network, regulating body
      homeostasis and controlling pain. To this effect, it is strongly wired to more
      rostral and caudal areas, in particular the brainstem periaqueductal grey, the
      locus coeruleus and the median raphe nuclei, all involved in autonomic and sleep
      mechanisms and also in the descending control of pain perception. The
      hypothalamus, especially its posterior regions, becomes activated during attacks
      of the trigeminal autonomic cephalalgias (TACs), while brainstem, especially
      dorsal pontine, activity shows up during migraine attacks. The hypothalamus and
      interconnected brainstem areas likely represent the neural sites responsible for
      the chronobiological features of some headaches, in particular the sleep-related
      attacks typical of the TACs, migraines and the hypnic headaches.

PMID- 17508171
TI  - Post-traumatic headache: emphasis on chronic types following mild closed head
      injury.
AB  - The syndrome known as chronic post-traumatic headache (CPTH) is controversial,
      particularly when it occurs following mild closed head injury or "whiplash".
      Problems with the diagnosis include issues related to classification,
      epidemiology, pathophysiology (psychogenic vs. organic) and treatment. In
      addition, there are cultural differences that may influence prevalence and
      diagnosis, as in some countries with little medico-legal recourse the disorder is
      virtually unknown. In this paper we review some of these controversies clinicians
      are left to formulate their own understanding based on available evidence and
      clinical experience. This is perhaps as it should be given that the best practice
      combines knowledge of the evidence with individual clinical experience.

PMID- 17508172
TI  - Recent advances in the pharmacogenomics of pain and headache.
AB  - Liability to spontaneous and experimental pain is genetically determined and
      there is considerable variability in the antinociceptive effects of drugs
      commonly used in treating pain conditions and migraine attacks. The causes for
      variability involve still unknown genetic aspects. Recently, a third gene, SCN1A,
      was discovered as a cause of familial hemiplegic migraine (FHM). Recent advances
      in the genetics of pain and pain disorders include the discovery of the role of
      the sodium ion channel SCN9A in neuropathic pain as well as in inability to
      experience pain, and of GTP cyclohydrolase (GCH1) in setting the sensitivity to
      pain in normal individuals and modulating liability to chronic pain. Catechol-O
      methyltransferase (COMT) and the cytochrome P450 variant allele CYP3A5 modulate
      the genetic response to opioid medications in humans. Variability in drug
      pharmacokinetics and adverse drug reactions of pain medications are also very
      much related to genetic variation, especially in CYP genes. Pharmacogenomic
      studies of headache and pain are still in their infancy, but these recent
      advances in the genetics of migraine and pain arguably hold the promise of
      individualised treatments and prevention of adverse drug reactions.

PMID- 17508173
TI  - Validation of AIDA Cefalee, a computer-assisted diagnosis database for the
      management of headache patients.
AB  - AIDA Cefalee is a database for the management of headache patients developed on
      behalf of the Italian Neurological Association for Headache Research (ANIRCEF).
      The system integrates a diagnostic expert system able to suggest the correct ICHD
      II diagnosis once all clinical characteristics of a patient's headache have been
      collected. The software has undergone a multicentre validation study to assess:
      its diagnostic accuracy; the impact of using the software on visit duration; the
      userfriendliness degree of the software interface; and patients' acceptability of
      computer-assisted interview. Five Italian headache centres participated in the
      study. The results of this study validate AIDA Cefalee as a reliable diagnostic
      tool for primary headaches that can improve diagnostic accuracy with respect to
      the standard clinical method without increasing the time length of visits even
      when used by operators with basic computer experience.

PMID- 17508174
TI  - Headache and anxiety-depressive disorder comorbidity: the HADAS study.
AB  - Psychiatric comorbidity (prevalence and types) was tested in a naturalistic
      sample of adult patients with pure migraine without aura, and in two control
      groups of patients, one experiencing pure tension-type headache and the other
      combined migraine and tension-type headaches. The study population included 374
      patients (158, 110 and 106) from nine Italian secondary and tertiary centres.
      Psychiatric comorbidity was recorded through structured interview and also
      screened with the Mini International Neuropsychiatry Interview (MINI). Only
      anxiety and depression were investigated. Psychiatric disorders were reported by
      49 patients (14.6%; 10.9% of patients with migraine, 12.8% of those with tension
      type headache and 21.4% of those with combined migraine and tension-type
      headaches). The MINI interview detected a depressive episode in 59.9% of patients
      with migraine, 68.3% of patients with tension-type headache and 69.6% of patients
      with combined migraine and tension-type headaches. Depression subtypes were
      significantly different across groups (p=0.03). Anxiety (mostly generalised) was
      reported by 18.4% of patients with migraine, 19.3% of patients with tension-type
      headache, and 18.4% of patients with combined migraine and tension-type
      headaches. The values for panic disturbance were 12.7, 5.5 and 14.2, and those
      for obsessive-compulsive disorders were 2.3, 1.1 and 9.4% (p=0.009). Based on
      these results, psychopathology of primary headache can be a reflection of the
      burden of the disease rather than a hallmark of a specific headache category.

PMID- 17508175
TI  - Allodynia in different forms of migraine.
AB  - About 60% of patients complain of cutaneous allodynia during migraine episodes,
      often in the periorbitary region of the pain side. Pre-clinical studies have
      shown that the underlying mechanism is sensitisation of primary nociceptors and
      central trigeminovascular neurons and that patients have a lower pain threshold
      for mechanical stimulation compared to controls. The objective of this study was
      to determine the prevalence of allodynia during headache attacks in different
      forms of migraine. The subjects were 221 outpatients consecutively evaluated in
      the Headache Center of the L. Sacco Hospital in Milan: 114 had only attacks of
      migraine without aura (MO), 63 had also attacks with aura (MA) and 44 patients
      with chronic migraine with and without drug overuse (CM). Presence of head
      allodynia was investigated by a semistructured interview. Statistical analysis
      was performed by chi square test with Bonferroni correction for multiple
      comparisons. Forty-seven out of 114 MO patients (41.2%) complained of allodynia
      during headache episodes, 41 out of 63 MA patients (65.0%), and 29 out of 44 CM
      patients (65.9%). A higher frequency of allodynia in MA and CM with respect to MO
      patients was observed (p<0.01 at chi square test). Allodynia was a common
      complaint in migraineurs, being present in more than 40% patients of each group.
      A higher frequency was observed in MA and in CM patients. This observation may
      suggest that both frequency of attacks and presence of aura episodes may
      contribute to induce changes in neuronal activation threshold thought to sustain
      allodynia.

PMID- 17508176
TI  - Why do we need NIRS in migraine?
AB  - Migraine patients may present altered values of the parameters related to their
      cerebral circulation. The non-invasive assessment of the autoregulation of such
      patients can be helpful in investigating the causes of migraine. We developed a
      joint analysis protocol based on transcranial Doppler (TCD) and near-infrared
      spectroscopy (NIRS) for assessing cerebral autoregulation. We tested 30 healthy
      subjects and 30 patients suffering from migraine without aura. We measured the
      baseline values of cerebral blood flow velocity (CBFV) in the middle cerebral
      arteries and the concentration of oxygenated (oxy-Hb) and reduced (deoxy-Hb)
      haemoglobin in brain tissue. Afterwards, the subjects performed a breath-holding
      (BH) task. In baseline conditions, we did not find significant difference between
      the CBFVs of healthy subjects and of migraineurs, even though the latter group
      showed a greater dispersion of the velocities (healthy: 70.6+/-6.8 cm/s;
      migraine: 71.5+/-14.4 cm/s). Strong differences in the CBFV were observable
      during the BH task: migraineurs showed a smaller BH index than controls (0.83+/
      0.55% vs. 1.29+/-0.71%; p<0.005) and a reduced increase of the oxy-Hb
      (migraineurs: 0.033+/-0.019 micromol/l/s; healthy: 0.055+/-0.037 micromol/l/s;
      p<0.01). Also, we found a different haemoglobin balancing during the BH phase
      between migraineurs and controls, revealing that migraineurs do not show a marked
      vasodilation as functional response to the CO(2) increase. We propose this joint
      analysis protocol to assess cerebral autoregulation of migraine patients, and
      suggest NIRS as a low-cost, easy, reliable and fast technique to deeply
      investigate cerebral coupling deregulations.

PMID- 17508177
TI  - Naproxen sodium in short-term prophylaxis of pure menstrual migraine:
      pathophysiological and clinical considerations.
AB  - We investigated the biological and clinical effects of naproxen sodium (NxS) in
      the short-term prophylaxis of pure menstrual migraine (PMM) in 25 women suffering
      from migraine without aura, occurring exclusively from 2 days before to 5 days
      after menstruation onset. Daily oral NxS (550 mg) from 7 days before menstruation
      to 7 days after menstruation onset was given for 3 menstrual cycles, and 5 days
      before menstruation to 5 days after menstruation onset over the next 3 menstrual
      cycles. In the month before initiation of treatment and in the third month of
      treatment, 6-keto-PGF1(alpha), TXB(2) and PGE(2) were measured in plasma before
      menstruation (day -2) and on the second day (day +2) after bleeding onset. In the
      20 women analysed, 6-keto-PGF1(alpha) was 17% lower (p<0.0001) and TXB(2) was 30%
      lower (p<0.0001) on day -2 during treatment than the same day pretreatment;
      TXB(2) was also lower (p<0.02) on day +2 during treatment than day +2
      pretreatment. The 6-keto-PGF1(alpha)/TXB(2) ratio was higher (p<0.01) on day -2
      treatment than day -2 pretreatment. PGE(2) levels were significantly lower
      (p<0.002) on day +2 than pre-treatment values on the same day. The number of
      attacks reduced from 1.7+/-0.11 pretreatment to 1.2+/-0.10 at the 3rd month
      (p<0.001), to 1.1+/-0.06 at the 6th month (p<0.0001). The duration reduced from
      25.6+/-4.42 h pretreatment to 15.5+/-4.43 h in the 3rd month (p<0.02), to 13.35+/
      4.26 h in the 6th month (p<0.001). The intensity reduced from 2.4+/-0.11
      pretreatment, to 1.2+/-0.10 in the 3rd month of treatment (p<0.0001), and 1.1+/
      0.07 in the 6th month (p<0.0001).

PMID- 17508178
TI  - Two symptomatic cases of cluster headache associated with internal carotid artery
      dissection.
AB  - Cluster headache is a clinical entity characterised by strictly unilateral head
      pain attacks accompanied by ipsilateral autonomic phenomena. We report two
      patients who had pain episodes mimicking cluster headache attacks, and who
      experienced a total or partial Horner's syndrome ipsilaterally to pain,
      persisting for 48 h after the last attack. A dissection of the ipsilateral
      internal carotid artery at the extra-intracranial passage was present in both
      cases. These cases highlight the need for extensive neuroradiological
      investigation in cluster headache patients when atypical features are present.

PMID- 17508179
TI  - Headache and spontaneous low cerebrospinal fluid pressure syndrome.
AB  - We examined 59 consecutive patients presenting between 1993 and 2006 at our
      centre diagnosed with headache associated with spontaneous intracranial
      hypotension syndrome (SIH). Thirty-six (61%) patients were women; the mean age
      was 47 years (range 20-68). Cerebral MRI with contrast confirmed SIH in all
      patients. Headache characteristics were obtained by direct semistructured
      interview; in a minority of cases information was completed retrospectively
      through a phone call. All SIH patients suffered from headache. Early recognition
      of SIH may avoid dangerous worsening due to delayed diagnosis. Orthostatic
      headache, the main symptom, suggests the diagnosis.

PMID- 17508180
TI  - Pharmacological treatment compared to behavioural treatment for juvenile tension
      type headache: results at two-year follow-up.
AB  - Recurrent headaches are common in children and adolescents. Most current
      investigations have employed limited modalities (either medication or
      behavioural) and few have included comparisons of different treatments. In this
      study relaxation training, administered in a limited contact format, and
      amitriptyline were compared for juvenile episodic tension-type headache. The
      clinical improvement was significant for both groups at 1- and 2-year follow-up;
      in particular for behavioural treatment, the patients came regularly for the
      sessions, practised routinely, and appeared to be compliant and accepting of
      treatment, although we did not assess this formally. In this group of patients
      the percentage of drop-outs was lower than in the pharmacological tratment.
      Although clinical results were similar in both groups, relaxation therapy seems
      to be more accepted than medication. The limited contact modality seems to be as
      useful as other behavioural approaches that require a greater investment of time
      (by patients and therapists), without unpleasant side effects. Because the sample
      sizes are small, these conclusions are tentative.

PMID- 17508181
TI  - Basilar-type migraine responsive to lamotrigine: three case reports.
AB  - Basilar-type migraine (BM) has been recognised in the revised International
      Classification of Headache Disorders as a distinct clinical entity (subtype of
      migraine with aura), characterised by disturbing migraine aura clearly
      originating from the brainstem or from both hemispheres simultaneously affected.
      It differs from familial and sporadic hemiplegic migraines by the absence of
      motor deficit. Lamotrigine has been shown to be effective in preventing migraine
      aura symptoms in typical aura and in some cases of BM. We tried lamotrigine in
      three female cases of BM.

PMID- 17508182
TI  - Focus on primary headaches: Recent advances in mechanisms and management.
      Proceedings of a conference, May 24-26, 2007, Stresa, Italy.

PMID- 17508183
TI  - Behavioural treatments: rationale and overview of the most common therapeutic
      protocols.
AB  - The view of headache as a psychophysiological disorder predates contemporary
      behavioural research and also the concept that psychosomatic illnesses are the
      result of specific emotional conflicts that eventually produce physical symptoms.
      Behavioural interventions include strategies for the identification and
      modification of behavioural headache triggers and the acquisition and use of self
      regulation skills aimed at prevention of headache episodes. Consequently,
      research in behavioural medicine has matured scientifically, although
      methodological imperfections have had an impact on contemporary headache
      management. The evidence suggests that the level of headache improvement with
      behavioural interventions may rival those obtained by using medications. As side
      effects and complications are minimal, these approaches are optimal options for
      young patients or for patients where the medications remain contraindicated.

PMID- 17508184
TI  - What does the evidence show? Efficacy of behavioural treatments for recurrent
      headaches in adults.
AB  - Behavioural treatments (predominantly biofeedback, relaxation and cognitive
      behavioural) have been utilised in headache management for nearly 4 decades. This
      paper examines their clinical efficacy, drawing upon 2 primary sources of
      evidence: meta-analytic and evidenced-based reviews. Behavioural treatments have
      demonstrated efficacy and have been endorsed by various reviewing groups, such as
      the US Headache Consortium. Outcomes from behavioural treatments appear to endure
      over longer-term follow-up intervals as well. Meta-analyses comparing behavioural
      and pharmacological treatments have revealed similar levels of outcome. The
      article closes with a brief discussion of methods investigators are exploring to
      make behavioural treatments more available and affordable to headache patients.

PMID- 17508185
TI  - Managing the "difficult" headache patient.
AB  - This article reviews the challenges in managing the more complicated headache
      patient. These patients often have chronic daily headache or high-frequency
      disabling migraine. Some patients have problems adhering to treatment regimens,
      which may reduce treatment efficacy and in some patients lead to medication
      misuse and overuse. Medication overuse may transform headache to daily and reduce
      the effectiveness of acute and preventive therapies. There is an elevated risk of
      mood and anxiety disorders in migraine, with even greater risk in chronic
      migraine. Personality disorders may further compromise treatment efforts. Current
      research is reviewed on these issues and clinical suggestions are provided for
      more effective management of these challenging patients.

PMID- 17508186
TI  - Integration of behavioural techniques into clinical practice.
AB  - Most clinicians agree that biobehavioural factors are important considerations in
      the assessment and treatment of headache patients. Attention to psychological and
      behavioural issues may become even a greater concern as the frequency of a
      patient's headaches increases, there is increased disability secondary to
      headaches and/or there is inadequate response to usually effective treatment. The
      present article will highlight biobehavioural factors that should be considered
      in the assessment process involving headache patients and will provide a model
      for integration of behavioural treatment into clinical practice.

PMID- 17508187
TI  - Pain pharmacology in migraine: focus on CGRP and CGRP receptors.
AB  - Over the last 100 years, the discovery of new analgesics has been a complex and
      difficult task. However, remarkable progress in the identification of novel
      molecular targets relevant for pain medicines has been reported. Here we will
      focus on the neuropeptide calcitonin generelated peptide (CGRP) and its receptors
      (CGRP-R) because of their role in migraine mechanism and migraine therapy. Recent
      preclinical and clinical data on the localisation, regulation and plasma levels
      of CGRP and on the function of CGRP-R will be summarised. The reviewed findings
      highlight the major function of CGRP in migraine and the use of CGRP-R
      antagonists as a novel approach for the treatment of migraine attack and,
      perhaps, as migraine prophylactic medicines.

PMID- 17508188
TI  - Biochemistry of neuromodulation in primary headaches: focus on anomalies of
      tyrosine metabolism.
AB  - Recent studies have suggested that abnormalities of dopamine and trace amines
      (tyramine, octopamine, and synephrine), products of tyrosine metabolism, may
      constitute the metabolic events that predispose to the occurrence of cluster
      headache (CH) and migraine attacks. This hypothesis is supported by the following
      evidences: the discovery of trace amine associated receptors (TAARs), expressed
      on the olfactory epithelium, amigdala, hypothalamus, periacqueductal gray, and
      the biochemical anomalies of dopamine and trace amines. The possible effects of
      these biochemical abnormalities on TAARs and dopamine receptors, located in
      different areas of CNS, may explain the behaviour (restlessness, anxiety and, at
      times, hypersexuality) and the autonomic signs during the painful attacks of CH,
      and the premonitory symptoms of migraine crisis (thirst, craving, yawning,
      alteration of smell, depression etc.).

PMID- 17508189
TI  - Neurophysiology and neuromodulators.
AB  - Migraine is an episodic brain disorder that results in significant morbidity.
      Antiepileptic drugs (neuromodulators) are increasingly recommended for migraine
      prevention because of placebo-controlled double-blind trials that prove them
      effective. Cortical spreading depression (CSD) is thought to be the
      pathophysiological correlate of the neurological symptoms in migraine with aura
      and neuromodulators may act on mechanisms involved in the initiation of CSD
      itself. Inhibition of trigeminocervical complex directly, or neurons that
      modulate sensory input, are also plausible mechanisms for the actions of
      neuromodulators in preventive therapy in migraine. Although it is unlikely that a
      single phenomenon serves as the only link between migraine and epilepsy, the
      neuronal hyperexcitability that may contribute to each condition may explain the
      effect of these drugs for both conditions.

PMID- 17508190
TI  - [Levobupivacaine for parturients undergoing elective caesarean delivery. A dose
      finding investigation].
AB  - BACKGROUND: The optimum intrathecal dose of hyperbaric levobupivacaine for spinal
      anaesthesia during elective caesarean section has not yet been investigated.
      METHODS: A total of 30 parturients undergoing elective caesarean section were
      included in this prospective, randomised, double-blind study. Parturients
      received either 7.5, 10 or 12.5 mg hyperbaric 0.5% levobupivacaine intrathecally.
      Analgesic, sensory and motor block characteristics as well as maternal and fetal
      levobupivacaine plasma concentrations were determined. RESULTS: Of the
      parturients receiving 7.5 mg levobupivacaine 40% required supplementary
      intravenous opioid analgesics intraoperatively and none achieved complete motor
      block. Compared to 7.5 mg levobupivacaine, 10 and 12.5 mg significantly prolonged
      duration of effective analgesia postoperatively (median: 45 vs. 81 and 96 min,
      respectively). Both maternal and fetal levobupivacaine plasma concentrations were
      low, with dose-dependent, statistically significant differences in maternal
      plasma concentrations. CONCLUSIONS: Levobupivacaine 7.5 mg did not provide
      satisfactory intraoperative analgesia in all parturients. There were no
      statistically significant differences between 10 and 12.5 mg levobupivacaine with
      respect to analgesic, sensory and motor block characteristics. Therefore, based
      on these data, 10 mg levobupivacaine is recommended for parturients undergoing
      elective caesarean section with spinal anaesthesia.

PMID- 17508191
TI  - [Mobile single-pass batch hemodialysis system in intensive care medicine.
      Reduction of costs and workload in renal replacement therapy].
AB  - This paper describes the introduction of a single-pass batch hemodialysis system
      for renal replacement therapy in a 14 bed intensive care unit. The goals were to
      reduce the workload of intensive care unit physicians using an alternative and
      simpler method compared to continuous veno-venous hemodiafiltration (CVVHDF) and
      to reduce the costs of hemofiltrate solutions (80,650 EUR per year in our clinic
      in 2005). We describe and evaluate the process of implementation of the system as
      well as the achieved and prospective savings. We conclude that a close
      cooperation of all participants (physicians, nurses, economists, technicians) of
      a hospital can achieve substantial benefits for patients and employees as well as
      reduce the economic burden of a hospital.

PMID- 17508192
TI  - [MicroRNA. A new level of immune regulation].

PMID- 17508193
TI  - Queue up, please! Spermathecal filling in the rove beetle Drusilla canaliculata
      (Coleoptera, Staphylinidae).
AB  - Most studies on insect sperm motility have been conducted in vitro using
      artificial environments outside the animal's body. Only little is known about the
      function of motile insect sperm at different sites within the male or female
      genital tracts. We dissected genital tracts of female rove beetles (Drusilla
      canaliculata) to show that spermatozoa use their own motility to migrate from the
      spermatophore into the spermatheca. Our dissection method allowed direct
      observation and filming of the spermathecal filling process inside the female's
      genital tract. Spermatozoa were found to enter the spermatheca individually,
      sometimes in groups of two or three. Although exhibiting only weak motility and
      no progressive motion in buffer solution, the spermatozoa inside the female show
      vigorous lashing and reach an average velocity of 47.5 microm s(-1). To gain
      mobility and speed, the spermatozoa likely utilize the relatively small diameter
      of the spermathecal duct to push themselves off the duct walls, rather than
      swimming freely in seminal fluid. The spermatozoa (approximately 1,250 microm)
      are considerably longer than the distance they have to travel along the
      spermathecal duct (approximately 800 microm). Our study provides the first direct
      observation of active sperm migration within the female of an insect stressing
      the importance of the genital tract as a prerequisite for functional sperm
      motility.

PMID- 17508194
TI  - [Coenzyme Q10 in Parkinson's disease. Symptomatic or neuroprotective effects?].
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      progressive loss of dopaminergic neurons within the substantia nigra pars
      compacta. Experimental and clinical data point to a defect of the mitochondrial
      respiratory chain as a major pathogenetic factor in PD. Although the restoration
      of mitochondrial respiration and reduction of oxidative stress by coenzyme Q(10)
      (CoQ10) could induce neuroprotective effects against the dopaminergic cell death
      in PD, these effects of CoQ10 could also improve the dopaminergic dysfunction.
      Thus CoQ10 might theoretically exert both neuroprotective and symptomatic effects
      in PD. Current data from controlled clinical trials are not sufficient to answer
      conclusively whether CoQ10 is neuroprotective in PD. Moreover, several open and
      controlled pilot studies on symptomatic effects of CoQ10 revealed inconsistent
      results. A recent randomized, double-blind, placebo-controlled trial showed no
      symptomatic effects in PD. CoQ10 is well tolerated and safe as both monotherapy
      and add-on medication in PD patients. The present review discusses the current
      knowledge on neuroprotective and symptomatic actions of CoQ10 in PD.

PMID- 17508195
TI  - [Behavioural addiction : an independent diagnostic category?].
AB  - Until recently knowledge was limited with respect to clinically relevant
      excessive reward-seeking behaviour such as pathological gambling, excessive
      shopping, and excessive working which meet diagnostic criteria of dependent
      behaviour. To date there is no consistent concept for diagnosis or treatment of
      excessive reward-seeking behaviour, and its classification is uncertain. However,
      the high number of subjects seeking treatment emphasises the importance of a
      clear conceptualisation of the so-called behavioural addictions and their
      successful treatment. Excessive reward-seeking behaviour may be used to regulate
      negative emotions. We suggest that, comparable to drug addiction, excessive
      reward-seeking behaviour can alleviate negative mood states and may be used as an
      (inadequate) stress coping strategy at the expense of active coping strategies.
      In the course of a pathological development, behavioural addiction may become the
      only available behavioural resource to cope with challenging developmental steps
      or social stress factors such as loneliness or anxiety.

PMID- 17508196
TI  - Prolonged preservation of nerve function in diabetic neuropathy in mice by herpes
      simplex virus-mediated gene transfer.
AB  - AIMS/HYPOTHESIS: The aim of this study was to determine whether prolonged
      expression of neurotrophin-3 (NT-3) in mice, achieved by herpes simplex virus
      (HSV)-mediated gene transfer with gene expression under the control of an HSV
      latency promoter, can provide protection against the progression of diabetic
      neuropathy over a 6 month period. MATERIALS AND METHODS: Mice with diabetes
      induced by streptozotocin were inoculated s.c. into both hind feet with a non
      replicating HSV vector containing the coding sequence for NT-3 under the control
      of the HSV latency-associated promoter 2 (LAP2) elements or with a control
      vector. Nerve function was evaluated by electrophysiological and behavioural
      measures over the course of 6 months after the onset of diabetes. RESULTS:
      Animals inoculated with the NT-3-expressing vector, but not animals inoculated
      with control vector, showed preservation of sensory and motor nerve amplitude and
      conduction velocity measured electrophysiologically, small fibre sensory function
      assessed by withdrawal from heat, autonomic function measured by pilocarpine
      induced sweating, skin innervation assessed by protein gene product 9.5 staining
      of axons, and density of calcitonin gene-related peptide terminals in the spinal
      cord measured by immunohistochemistry 5.5 months after vector inoculation.
      CONCLUSIONS/INTERPRETATION: These results indicate that the continuous production
      of NT-3 by LAP2-driven expression of the transgene from an HSV vector over a 6
      month period protects against progression of diabetic neuropathy in mice, and
      provide a proof-of-principle demonstration for the development of a novel therapy
      for preventing the progression of diabetic neuropathy.

PMID- 17508197
TI  - Reactive oxygen species mediate a cellular 'memory' of high glucose stress
      signalling.
AB  - AIMS/HYPOTHESIS: A long-term 'memory' of hyperglycaemic stress, even when
      glycaemia is normalised, has been previously reported in endothelial cells. In
      this report we sought to duplicate and extend this finding. MATERIALS AND
      METHODS: HUVECs and ARPE-19 retinal cells were incubated in 5 or in 30 mmol/l
      glucose for 3 weeks or subjected to 1 week of normal glucose after being exposed
      for 2 weeks to continuous high glucose. HUVECs were also treated in this last
      condition with several antioxidants. Similarly, four groups of rats were studied
      for 3 weeks: (1) normal rats; (2) diabetic rats not treated with insulin; (3)
      diabetic rats treated with insulin during the last week; and (4) diabetic rats
      treated with insulin plus alpha-lipoic acid in the last week. RESULTS: In human
      endothelial cells and ARPE-19 retinal cells in culture, as well as in the retina
      of diabetic rats, levels of the following markers of high glucose stress remained
      induced for 1 week after levels of glucose had normalised: protein kinase C-beta,
      NAD(P)H oxidase subunit p47phox, BCL-2-associated X protein, 3-nitrotyrosine,
      fibronectin, poly(ADP-ribose) Blockade of reactive species using different
      approaches, i.e. the mitochondrial antioxidant alpha-lipoic acid, overexpression
      of uncoupling protein 2, oxypurinol, apocynin and the poly(ADP-ribose) polymerase
      inhibitor PJ34, interrupted the induction both of high glucose stress markers and
      of the fluorescent reactive oxygen species (ROS) probe CM-H(2)DCFDA in human
      endothelial cells. Similar results were obtained in the retina of diabetic rats
      with alpha-lipoic acid added to the last week of normalised glucose.
      CONCLUSIONS/INTERPRETATION: These results provide proof-of-principle of a ROS
      mediated cellular persistence of vascular stress after glucose normalisation.

PMID- 17508198
TI  - Insulin glargine supplementation during early management phase of diabetic
      ketoacidosis in children.
AB  - OBJECTIVE: To study the effect of subcutaneous administration of insulin glargine
      on the rate of resolution of acidosis and intravenous insulin infusion
      requirement in children with moderate and severe diabetic ketoacidosis (DKA).
      STUDY DESIGN: Retrospective cohort study. SETTING: Pediatric intensive care unit
      of a university-based children's hospital. PATIENTS: Children with moderate to
      severe DKA admitted between March 2001 and February 2003. RESULTS: The outcomes
      of children who received 0.3 units/kg of subcutaneous insulin glargine in the
      first 6 h of management in addition to the standard treatment (n=12) were
      compared with those of children who received standard treatment alone (n=59).
      Measured outcomes included dose of intravenous insulin required, duration of
      insulin infusion and acidosis correction time. The two groups were similar in
      demographics and severity of illness. The mean time for acidosis correction
      (venous pH>or=7.3) in the insulin glargine group was shorter than the standard
      therapy group (12.4+/-2.9 h and 17.1+/-6.2 h respectively, p<0.001). The insulin
      infusion time was shorter in the insulin glargine group (14.8+/-6.0 h vs 24.4+/
      9.0 h, p<0.001). There was a trend towards shorter total hospital stay in the
      glargine group (3.2+/-1.0 days vs 3.72+/-1.06 days). CONCLUSIONS: In our small
      series of children with moderate and severe DKA, supplementing with subcutaneous
      insulin glargine led to a faster resolution of acidosis without any adverse
      effects. This could potentially lead to a shorter need for insulin infusion and a
      shorter ICU length of stay.

PMID- 17508199
TI  - Echocardiographic prediction of volume responsiveness in critically ill patients
      with spontaneously breathing activity.
AB  - OBJECTIVE: In hemodynamically unstable patients with spontaneous breathing
      activity, predicting volume responsiveness is a difficult challenge since the
      respiratory variation in arterial pressure cannot be used. Our objective was to
      test whether volume responsiveness can be predicted by the response of stroke
      volume measured with transthoracic echocardiography to passive leg raising in
      patients with spontaneous breathing activity. We also examined whether common
      echocardiographic indices of cardiac filling status are valuable to predict
      volume responsiveness in this category of patients. DESIGN AND SETTING:
      Prospective study in the medical intensive care unit of a university hospital.
      PATIENTS: 24 patients with spontaneously breathing activity considered for volume
      expansion. MEASUREMENTS: We measured the response of the echocardiographic stroke
      volume to passive leg raising and to saline infusion (500 ml over 15 min). The
      left ventricular end-diastolic area and the ratio of mitral inflow E wave
      velocity to early diastolic mitral annulus velocity (E/Ea) were also measured
      before and after saline infusion. RESULTS: A passive leg raising induced increase
      in stroke volume of 12.5% or more predicted an increase in stroke volume of 15%
      or more after volume expansion with a sensitivity of 77% and a specificity of
      100%. Neither left ventricular end-diastolic area nor E/Ea predicted volume
      responsiveness. CONCLUSIONS: In our critically ill patients with spontaneous
      breathing activity the response of echocardiographic stroke volume to passive leg
      raising was a good predictor of volume responsiveness. On the other hand, the
      common echocardiographic markers of cardiac filling status were not valuable for
      this purpose.

PMID- 17508200
TI  - Can one predict fluid responsiveness in spontaneously breathing patients?

PMID- 17508201
TI  - Can dynamic indicators help the prediction of fluid responsiveness in
      spontaneously breathing critically ill patients?
AB  - OBJECTIVE: To investigate whether the respiratory changes in arterial pulse
      (DeltaPP) and in systolic pressure (DeltaSP) could predict fluid responsiveness
      in spontaneously breathing (SB) patients. Because changes in intrathoracic
      pressure during spontaneous breathing (SB) might be insufficient to modify
      loading conditions of the ventricles, performances of indicators were also
      assessed during a forced respiratory maneuver. DESIGN: Prospective interventional
      study. SETTING: A 34-bed university hospital medico-surgical ICU. PATIENTS AND
      PARTICIPANTS: Thirty-two SB patients with clinical signs of hemodynamic
      instability. INTERVENTION: A 500-ml volume expansion (VE). MEASUREMENTS AND
      RESULTS: Cardiac index, assessed using transthoracic echocardiography, increased
      by at least 15% after VE in 19 patients (responders). At baseline, only dynamic
      indicators were higher in responders than in nonresponders (13+/-5% vs. 7+/-3%,
      p=0.003 for DeltaPP and 10+/-4% vs. 6+/-2%, p=0.002 for DeltaSP). Moreover, they
      significantly decreased after VE (11+/-5% to 6+/-4%, p<0.001 for DeltaPP and 8+/
      4% to 6+/-3%, p<0.001 for DeltaSP). DeltaPP and DeltaSP areas under the ROC curve
      were high (0.81+/-0.08 and 0.82+/-0.08; p=0.888, respectively). A DeltaPP>or=12%
      predicted fluid responsiveness with high specificity (92%) but poor sensitivity
      (63%). The forced respiratory maneuver reproducing a dyspneic state decreased the
      predictive power. CONCLUSIONS: Due to their lack of sensitivity and their
      dependence to respiratory status, DeltaPP and DeltaSP are clearly less reliable
      to predict fluid responsiveness during SB than in mechanically ventilated
      patients. However, when their baseline value is high without acute right
      ventricular dysfunction in a participating patient, a positive response to fluid
      is likely.

PMID- 17508202
TI  - Diagnosis of central hypovolemia by using passive leg raising.
AB  - OBJECTIVE: Suspected central hypovolemia is a frequent clinical situation in
      hospitalized patients, and no simple bedside diagnostic test in spontaneously
      breathing patients is available. We tested the value of passive leg raising to
      predict hemodynamic improvement after fluid expansion in patients with suspected
      central hypovolemia. DESIGN AND SETTING: Prospective study in four intensive care
      units at the Amiens university hospital. Thirty-four spontaneously breathing
      patients with suspected hypovolemia were included and were classified as
      responders (cardiac output increased by 12% or more after fluid expansion) or
      nonresponders. Patients were analyzed in the supine position during 30 degrees
      leg raising and after fluid expansion. MEASUREMENTS AND RESULTS: Stroke volume
      and cardiac output determined by echocardiographic and Doppler techniques and
      heart rate and blood pressure were measured at baseline, during passive leg
      raising and after fluid expansion. An increase of cardiac output or stroke volume
      by 12% or more during passive leg raising was highly predictive of central
      hypovolemia (AUC 0.89+/-0.06, 95% CI 0.73-0.97 for cardiac output and AUC 0.9+/
      0.06, 95% CI 0.74-0.97 for stroke volume). Sensitivity and specificity values
      were 63% and 89% for cardiac output and 69%, 89% for stroke volume respectively.
      A close correlation (r=0.75; p<0.0001) was observed between cardiac output
      changes during leg raising and changes in cardiac output after fluid expansion.
      CONCLUSIONS: Bedside measurement of cardiac output or stroke volume by Doppler
      techniques during passive leg raising was predictive of a positive hemodynamic
      effect of fluid expansion in spontaneously breathing patients with suspected
      central hypovolemia.

PMID- 17508204
TI  - The Ninth International Symposium on Kinetics in Analytical Chemistry (9th KAC).

PMID- 17508203
TI  - Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 4,4 
      [1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] based on
      the OECD draft protocols.
AB  - We performed an uterotrophic assay, the Hershberger assay, and a 28-day repeated
      dose toxicity study (enhanced OECD test guideline No. 407) of 4,4 -[1-[4-[1-(4
      hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] based on the OECD
      draft protocols. In the uterotrophic assay, female SD rats were subcutaneously
      injected with the chemical at doses of 0, 100, 300, and 1,000 mg/kg on each of 3
      days from postnatal day 20 to day 22, and the uterine weight of rats given the
      1,000 mg/kg dose of the test chemical plus ethinyl estradiol decreased. In the
      Hershberger assay, the test chemical was orally administered at doses of 0, 100,
      300, and 1,000 mg/kg day to castrated male SD rats for ten consecutive days
      beginning on postnatal day 56, and no changes were observed. On the other hand,
      when the test chemical was orally administered at doses 0, 100, 300, and 1,000
      mg/kg day for at least 28 days, a decrease in LH values in rats of both sexes and
      a decrease in FSH and estradiol values in female rats were detected in the 1,000
      mg/kg group, and abnormal estrous cycles, uterine glandular atrophy, persistence
      of ovarian corpora lutea, vaginal epithelial mucification, and mammary glandular
      hyperplasia were also observed in one female rat in the 1,000 mg/kg group.
      Therefore, the uterotrophic assay used in this study showed that the chemical has
      the estrogen-antagonist properties, and some potentially endocrine-mediated
      effects were detected in growing rats based on the results of the enhanced OECD
      test guideline No. 407. However, the changes were observed in rats given a high
      dose of the chemical, 1,000 mg/kg day.

PMID- 17508205
TI  - Fast, sensitive and cost-effective detection of nerve agents in the gas phase
      using a portable instrument and an electrochemical biosensor.
AB  - The nerve agents are chemical warfare agents known to be used during terrorist
      attacks. An inexpensive and portable system to be used by first responders and
      military personnel is of interest owing to the continuing threat of possible
      terrorist attacks. Amperometric biosensors based on cholinesterase inhibition
      show such potentialities. In this work butyrylcholinesterase was immobilized onto
      screen-printed electrodes modified with Prussian blue and the nerve agent
      detection was performed by measuring the residual activity of enzyme. The
      optimized biosensor was tested with sarin and VX standard solutions, showing
      detection limits of 12 and 14 ppb (10% of inhibition), respectively. The
      enzymatic inhibition was also obtained by exposing the biosensors to sarin in gas
      phase. Two different concentrations of sarin gas (0.1 and 0.5 mg m(-3)) at
      different incubation times (from 30 s up to 10 min) were tested. It is possible
      to detect sarin at a concentration of 0.1 mg m(-3) with 30-s incubation time,
      with a degree of inhibition of 34%, which match the legal limits (immediate
      danger to life and health).

PMID- 17508206
TI  - Trace analysis of sulfonylurea herbicides and their metabolites in water using a
      combination of off-line or on-line solid-phase extraction and liquid
      chromatography-tandem mass spectrometry.
AB  - Two alternatives for the rapid simultaneous quantification of six sulfonylurea
      herbicides and five of their main degradation products in natural water are
      proposed. For concentration, the compounds were extracted on a polystyrene
      divinylbenzene solid phase under pH and elution conditions that suppressed any
      hydrolysis. The eluates were analysed by liquid chromatography coupled to
      electrospray tandem mass spectrometry within 20 min. The whole method was
      validated and shown to give no hydrolysis artefacts. The application of off-line
      and on-line SPE of sulfonylureas enabled the 0.1 microg L(-1) and 1 ng L(-1) LOQ
      levels to be reached, respectively. The on-line SPE-LC-MS-MS method allowed the
      accurate quantitation of all sulfonylureas and three degradation products at 0.1
      microg L(-1) or below in natural water, with an average repeatability of 8%.

PMID- 17508207
TI  - Regulations relating to mycotoxins in food: perspectives in a global and European
      context.
AB  - Regulations relating to mycotoxins have been established in many countries to
      protect the consumer from the harmful effects of these compounds. Different
      factors play a role in the decision-making process of setting limits for
      mycotoxins. These include scientific factors, for example the availability of
      toxicological data and occurrence data, detailed knowledge about possibilities
      for sampling and analysis, and socio-economic issues. By the end of 2003,
      approximately 100 countries (covering approximately 85% of the world's
      inhabitants) had specific regulations or detailed guidelines for mycotoxins in
      food. The regulations were related to aflatoxins (B(1), B(2), G(1) and G(2)),
      aflatoxin M(1), trichothecenes (deoxynivalenol, diacetoxyscirpenol, T-2 toxin and
      HT-2 toxin), fumonisins (B(1), B(2), and B(3)), agaric acid, ergot alkaloids,
      ochratoxin A, patulin, phomopsins, sterigmatocystin, and zearalenone. In Europe,
      and in particular in the EU, regulatory and scientific interest in mycotoxins has
      undergone a development in the last decade from autonomous national activity
      towards more EU-driven activity with a structural and network character.
      Harmonized EU limits now exist for 40 mycotoxin-food combinations. It is expected
      this number will grow in 2007 to approximately 50. The direct or indirect
      influence of European organizations and programs on the EU mycotoxin regulatory
      developments is significant. They include the European Food Safety Authority, the
      Scientific Cooperation on Questions relating to Food, the Rapid Alert System for
      Food and Feed, the creation of an EU Community Reference Laboratory for
      Mycotoxins and a mandate of the EC to the European Standardization Committee in
      methods for analysis for mycotoxins in food. Large pan-European research and
      networking projects as "BioCop" and "MoniQA" are also important.

PMID- 17508208
TI  - Viewing the body modulates tactile receptive fields.
AB  - Tactile discrimination performance depends on the receptive field (RF) size of
      somatosensory cortical (SI) neurons. Psychophysical masking effects can reveal
      the RF of an idealized "virtual" somatosensory neuron. Previous studies show that
      top-down factors strongly affect tactile discrimination performance. Here, we
      show that non-informative vision of the touched body part influences tactile
      discrimination by modulating tactile RFs. Ten subjects performed spatial
      discrimination between touch locations on the forearm. Performance was improved
      when subjects saw their forearm compared to viewing a neutral object in the same
      location. The extent of visual information was relevant, since restricted view of
      the forearm did not have this enhancing effect. Vibrotactile maskers were placed
      symmetrically on either side of the tactile target locations, at two different
      distances. Overall, masking significantly impaired discrimination performance,
      but the spatial gradient of masking depended on what subjects viewed. Viewing the
      body reduced the effect of distant maskers, but enhanced the effect of close
      maskers, as compared to viewing a neutral object. We propose that viewing the
      body improves functional touch by sharpening tactile RFs in an early
      somatosensory map. Top-down modulation of lateral inhibition could underlie these
      effects.

PMID- 17508209
TI  - New role of C-terminal 30 amino acids on the insoluble chitin hydrolysis in
      actively engineered chitinase from Vibrio parahaemolyticus.
AB  - A chitinase (VpChiA) and its C-terminal truncated G589 mutant (VpChiAG589) of
      Vibrio parahaemolyticus were cloned by polymerase chain reaction (PCR)
      techniques. To study the role of the C-terminal 30 amino acids of VpChiA in the
      enzymatic hydrolysis of chitin, both the recombinant VpChiA and VpChiAG589
      encoded in 1,881 and 1,791 bp DNA fragments, respectively, were expressed in
      Escherichia coli using the pET-20b(+) expression system. The His-Tag affinity
      purified VpChiA and VpChiAG589 enzymes had a calculated molecular mass of 65,713
      and 62,723 Da, respectively. The results of biochemical characterization
      including kinetic parameters, spectroscopy of fluorescence and circular
      dichroism, chitin-binding and hydrolysis, and thermostability, both VpChiA and
      VpChiAG589, had very similar physicochemical properties such as the optimum pH
      (6), temperature (40 degrees C), and kinetic parameters of Km and kcat against
      the 4MU-(GlcNAc)(2) or 4MU-(GlcNAc)(3) soluble substrates. The significant
      increase of thermostability and the drastic decrease of the hydrolyzing ability
      of VpChiAG589 toward the insoluble alpha-chitin substrate suggested that a new
      role could be played by the C-terminal 30 amino acids.

PMID- 17508210
TI  - Muscle atrophy as a consequence of rotator cuff tears: should we compare the
      muscles of the rotator cuff with those of the deltoid?
AB  - PURPOSE: The quantitative assessment of muscle atrophy has a degree of importance
      in prognosticating rotator cuff treatment. However, it has been conjectured that
      muscle fat increases with aging. Therefore, we thought that the quantitative
      assessment of the supraspinatous would be better if made in comparison with a
      standard of reference such as the deltoid. Consequently, we performed a two-part
      study, first evaluating supraspinatous changes compared with the deltoid in
      "normals" with aging, and second, determining if in patients with cuff tears the
      supraspinatous fat exceeds that of the deltoid. MATERIALS AND METHODS: In part 1,
      we studied 50 patients stratified by decade. In the first sitting, two blinded
      independent observers quantitatively graded the deltoid (with the supraspinatous
      obscured) and in the second sitting the same two observers quantitatively graded
      the supraspinatous (with the deltoid obscured). In part 2 of the study, we
      evaluated patients with moderate rotator cuff tears (>2 cm) and performed the
      same blinded, two-sitting, quantitative assessment (with the comparison muscle
      obscured). RESULTS: We found that muscle atrophy increases with age in patients
      without tears (0.011/0.028 U/year), although to a greater degree in the deltoid
      (p = 0.032). Also, in similarly aged patients, quantitative scores of the deltoid
      closely matched those of the supraspinatous (p = 0.071). Notably, however, in
      patients with large tears, the supraspinatous showed significant changes
      disproportionate to those of the deltoid, regardless of patient age (p = 0.044).
      CONCLUSION: In the presence of a normal rotator cuff, fatty infiltration
      increases with age. Age-related changes occur more frequently in the deltoid,
      verifying this muscle's potential as a standard of reference. With cuff tears,
      supraspinatous atrophy was disproportionate to that of the deltoid. Therefore,
      systematic assessment of supraspinatous muscle atrophy may be more reliable using
      the deltoid as a control for comparison than assessing it in isolation.

PMID- 17508212
TI  - Consensus nomenclature: its time has come.

PMID- 17508211
TI  - Computer-aided joint space analysis of the metacarpal-phalangeal and proximal
      interphalangeal finger joint: normative age-related and gender-specific data.
AB  - PURPOSE: The purpose of the study was to provide reference data for computer
      aided joint space analysis based on a semi-automated and computer-aided
      diagnostic system for the measurement of metacarpal-phalangeal and proximal
      interphalangeal finger joint widths; additionally, the determination of sex
      differences and the investigation of changes in joint width with age were
      evaluated. PATIENTS AND METHODS: Eighty hundred and sixty-nine patients (351
      female and 518 male) received radiographs of the hand for trauma and were
      screened for a host of conditions known to affect the joint spaces. All
      participants underwent measurements of joint space distances at the metacarpal
      phalangeal articulation (JSD-MCP) from the thumb to the small finger and at the
      proximal-interphalangeal articulation (JSD-PIP) from the index finger to the
      small finger using computer-aided diagnosis technology with semi-automated edge
      detection. RESULTS: The study revealed an annual narrowing of the JSD of 0.6% for
      the JSD-MCP and for the JSD-PIP. Furthermore, the data demonstrated a notable age
      related decrease in JSD, including an accentuated age-related joint space
      narrowing in women for both articulations. Additionally, males showed a
      significantly wider JSD-MCP (+11.1%) and JSD-PIP (+15.4%) compared with the
      female cohort in all age groups. CONCLUSION: Our data presented gender-specific
      and age-related normative reference values for computer-aided joint space
      analysis of the JSD-MCP and JSD-PIP that could be used to identify disease
      related joint space narrowing, particularly in patients with osteoarthritis and
      rheumatoid arthritis commonly involving the peripheral small hand joints.

PMID- 17508213
TI  - Correlation between promoter hypermethylation of GSTP1 and response to
      chemotherapy in diffuse large B cell lymphoma.
AB  - Glutathione-S-transferase P1 (GSTP1) and O6-methylguanine DNA methyltransferase
      (MGMT) are involved in drug-resistant to chemotherapeutic agents such as
      doxorubicin. In this study, prognostic significance of promoter hypermethylation
      and mRNA and protein expression of GSTP1 and MGMT together with promoter
      hypermethylation of death-associated protein kinase (DAPK) in diffuse large B
      cell lymphoma (DLBCL) was analyzed. Fifty-three patients with DLBCL, 24 men and
      29 women, with age ranging from 23 to 91 (median 65), were analyzed. Genomic DNA
      and total RNA extracted from frozen samples of DLBCL were analyzed by methylation
      specific polymerase chain reaction and quantitative reverse transcription
      polymerase chain reaction (RT-PCR) to determine promoter hypermethylation and
      mRNA expression of GSTP1, MGMT, and DAPK. Immunohistochemical analysis was
      performed to determine GSTP1 and MGMT expression at the protein level. Promoter
      hypermethylation of GSTP1, MGMT, and DAPK was detected in 12 (22.6%), 21 (39.6%),
      and 36 (67.9%) of 53 patients, respectively. Quantitative RT-PCR and
      immunohistochemistry did not show a correlation between methylation status and
      mRNA and protein expression of GSTP1 and MGMT. Patients with GSTP1 promoter
      hypermethylation showed a better 5-year overall survival rate than those without
      (100 vs 62.2%; p < 0.05). However, GSTP1 promoter hypermethylation was not an
      independent prognosticator in multivariate analysis. Methylation status of GSTP1
      could be an indicator of drug response and a prognosticator for DLBCL.

PMID- 17508214
TI  - Evaluation of ER and Ki-67 proliferation index as prognostic factors for survival
      following neoadjuvant chemotherapy with doxorubicin/docetaxel for locally
      advanced breast cancer.
AB  - BACKGROUND: The aim of the study was to identify reliable predictive biological
      markers for treatment outcome following neoadjuvant adriamycin/docetaxel (AT)
      chemotherapy in locally advanced breast cancer patients. MATERIALS AND METHODS:
      This study was a phase II study on AT neoadjuvant chemotherapy in locally
      advanced breast cancer patients. Patients received 50 mg/m(2) of doxorubicin
      intravenously (IV) over 15 min followed by docetaxel 75 mg/m(2) infused over 1 h,
      repeated every 3 weeks for three cycles. Surgery was performed within 3-4 weeks
      following the last cycle of chemotherapy. We analyzed the pre-treatment and post
      treatment expression levels of ER, PgR, HER-2, Ki-67 proliferation index, and p53
      and examined the correlation between the markers and clinical parameters with
      treatment response, overall survival and relapse-free survival following
      neoadjuvant treatment. RESULTS: From July 2001 to September 2004, 61 patients
      were enrolled. The meaningful parameters adversely influencing survival were post
      treatment ER(-) status (P = 0.013) and post-treatment Ki-67 index above 1.0% (P =
      0.013). At the multivariate level, the post-treatment Ki-67 proliferation index <
      or = 1.0 was the only meaningful prognostic factor for better survival (P =
      0.033). Notably, tumors with Ki-67 index < or = 1.0 were more likely to express
      ER with statistical significance (P = 0.002). Tumors with ER(+) and Ki-67 index <
      or = 1.0 showed the highest survival rate, followed by ER(+) and Ki-67 index >
      1.0%, ER(-) and Ki-67 < or = 1.0%, and ER(-) and Ki-67 > 1.0% with the worst
      survival (P = 0.033). CONCLUSION: Collectively, post-treatment ER status and Ki
      67 proliferation index were prognostic of overall survival following neoadjuvant
      AT chemotherapy.

PMID- 17508215
TI  - Combined expression of chitinase and lipid transfer protein genes in transgenic
      carrot plants enhances resistance to foliar fungal pathogens.
AB  - Two pathogenesis-related (PR) protein genes consisting of a barley chitinase (chi
      2) and a wheat lipid-transfer-protein (ltp) were introduced singly and in
      combination into carrot plants via Agrobacterium-mediated transformation using
      the phosphinothricin acetyl transferase (bar) gene as a selectable marker. Over
      75% of regenerated plants were confirmed to be positive for the transgenes by PCR
      and RT-PCR and were resistant to the herbicide Liberty (0.2%, v/v). Northern
      analysis and immunoblotting confirmed the expression of the transgenes in about
      70% of the plants, with variable expression levels among individual lines.
      Southern analysis revealed from one to three copies of each transgene. Transgenic
      plants were inoculated with two necrotrophic foliar fungal pathogens, Alternaria
      radicicola and Botrytis cinerea, and showed significantly higher resistance when
      both PR genes were expressed compared to single-gene transformants. The level of
      disease reduction in plants expressing both genes was 95% for Botrytis and 90%
      for Alternaria infection compared to 40-50% for single-gene transformants. The
      chi2 and ltp genes could be deployed in combination in other crop plants to
      significantly enhance resistance to necrotrophic fungal pathogens.

PMID- 17508216
TI  - Foregut atresias and bile duct anomalies: rare, infrequent or common?!
AB  - The association of foregut atresias and bile duct anomalies is reportedly rare.
      We encountered five referrals within 2 years where the secondary diagnosis was
      missed at operation. Four patients initially presented on antenatal scans as a
      foregut atresia whereas the fifth presented at nine years with abdominal pain due
      to a choledochal cyst. The biliary anomalies (cholecysto-hepatic duct, liver cyst
      and choledochal cysts) in the first four presented as postoperative jaundice
      during infancy whereas the fifth patient developed subacute intestinal
      obstruction due to congenital duodenal stenosis at fifteen years. In the patients
      with duodenal atresia neither did the preoperative X ray reveal any distal bowel
      gas nor did the subsequent intraoperative cholangiograms reveal bifid common bile
      duct or pancreato-biliary malunion. Atresias were corrected by primary repair
      (duodenoduodenostomy for congenital duodenal obstruction in four patients and
      disconnection/ligation of tracheo-oesophageal fistula with oesophageal
      anastomosis in one patient). The biliary anomalies were corrected by excision of
      the abnormal bile ducts (choledochal cyst/liver cyst/cholecystectomy) with Roux
      en Y hepaticojejunostomy. All patients are asymptomatic and liver function and
      biliary dilatation has normalised. The association of foregut atresias and bile
      duct anomalies is not as rare as previously reported. Antenatal ultrasound
      suggesting either a foregut or a biliary anomaly should alert one to the
      association. Full radiological and/or imaging investigation may be indicated
      prior to corrective surgery of the primary anomaly.

PMID- 17508217
TI  - Total laparoscopic hysterectomy: a 5-year experience.
AB  - AIM: To evaluate our surgical technique with regards to the success of total
      laparoscopic hysterectomy (TLH) for the removal of the uterus by analysing its
      intra-operative and post-operative outcomes and complications in the hope of
      reducing their occurrence. METHODS: Retrospective study based on TLH operations
      performed from January 2001 to December 2005. The KOH Colpotomizer System and the
      RUMI Uterine Manipulator were used. RESULTS: Five hundred and twelve women
      consented for TLH. Five hundred and three women (98.2%) had successful TLH with
      three mini-laparotomy and six laparotomy conversions (1.8% failure rate). Mean
      uterine size was 11 cm (5-17). Mean operating time was 133 min (40-257). Mean
      blood loss was 309 ml (50-1,500). Twenty patients (4%) required blood transfusion
      (five excessive bleeding). Injuries include bowel injury (5), bladder (2),
      uterine perforation (1), ureterovaginal fistula (1) and vaginal laceration (5).
      Post-operative complications include pyrexia (36), umbilical wound infection (5),
      urinary tract infection (UTI) (4) and vault haematoma (3). Mean hospital stay was
      2.7 days (1-10). Eighteen patients (3.6%) were readmitted for vaginal bleeding
      (10), vault haematoma (2), UTI (1), anxiety (3), giddiness (1) and ureterovaginal
      fistula (1). Twenty-three women (4.5%) encountered major complications
      (laparotomy conversion, excessive bleeding requiring blood transfusion,
      hemorrhage > or =1,000 ml, ureteric injury, bowel injury and pulmonary embolus)
      which compares favourably with other centres (4-11%). Our mean operating time,
      mean estimated blood loss, mean hospital stay and readmission rate are
      comparable. CONCLUSION: TLH with adequate training is associated with low
      morbidity, few complications and a high success rate.

PMID- 17508218
TI  - Hau-Pax6A expression in the central nervous system of the leech embryo.
AB  - The leech Helobdella sp. (Austin) has two genes of the Pax6 subfamily, one of
      which is characterized in detail. Hau-Pax6A was expressed during embryonic
      development in a pattern similar to other bilaterian animals. RNA was detected in
      cellular precursors of the central nervous system (CNS) and in peripheral cells
      including a population associated with the developing eye. The CNS of the mature
      leech is a ventral nerve cord composed of segmental ganglia, and embryonic Hau
      Pax6A expression was primarily localized to the N teloblast lineage that
      generates the majority of ganglionic neurons. Expression began when the ganglion
      primordia were four cells in length and was initially restricted to a single
      cell, n(s).a, whose descendants will form the ganglion's anterior edge. At later
      stages, the Hau-Pax6A expression pattern expanded to include additional CNS
      precursors, including some descendants of the O teloblast. Expression persisted
      through the early stages of ganglion morphogenesis but disappeared from the
      segmented body trunk at the time of neuronal differentiation. The timing and
      iterated pattern of Hau-Pax6A expression in the leech embryo suggests that this
      gene may play a role in the segmental patterning of CNS morphogenesis.

PMID- 17508219
TI  - Oblimersen and alpha-interferon in metastatic renal cancer: a phase II study of
      the California Cancer Consortium.
AB  - PURPOSE: Oblimersen is an 18-base oligodeoxynucleotide encoding antisense to the
      gene for bcl-2, an anti-apoptotic protein that is upregulated in renal and other
      cancers. This study was designed to evaluate the combination of oblimersen with
      alpha-Interferon in advanced renal cancer. Trial endpoints were antitumor
      efficacy and toxicity, pharmacokinetics, and evidence of apoptosis in peripheral
      blood mononuclear cells. METHODS: Patients with measurable advanced renal cancer
      and 0-1 prior therapy were eligible. Treatment consisted of oblimersen, 7
      mg/kg/day, as a continuous intravenous infusion 7 days of every 14 day cycle,
      plus alpha-IFN, 5 million units/m(2) subcutaneously, days 4 and 6 of the first
      oblimersen infusion, then thrice weekly. Blood for laboratory correlates was
      collected before treatment, during oblimersen, and during therapy with both
      agents. RESULTS: Twenty-three patients were enrolled, five of whom had prior
      systemic therapy (three with prior high-dose interleukin-2). The median number of
      treatment cycles was 4 (range 1-12). One patient had a partial response lasting
      2.5 months. The Grade 3-4 toxicities were fatigue, fever, myelosuppression,
      hepatic enzyme and metabolic abnormalities. Laboratory analyses of CD3+
      lymphocyte apoptotic markers demonstrated no change between pre-treatment and on
      treatment levels of bcl-2 or Annexin/PI positivity by flow cytometry. Mean
      oblimersen steady-state plasma concentration and clearance was 2.3 +/- 0.9
      microg/ml and 0.15 +/- 0.07 l/h/kg, respectively. CONCLUSIONS: Oblimersen given
      in this dose and schedule with alpha-IFN does not appear sufficiently active to
      warrant further study in advanced renal cancer. Combinations with newer targeted
      agents may show greater promise.

PMID- 17508220
TI  - Proliferative capacity of enterochromaffin cells in guinea-pigs with experimental
      ileitis.
AB  - Enterochromaffin (EC) cells regulate gut motility and secretion in response to
      luminal stimuli, via the release of serotonin (5-HT). Inflammatory bowel disease
      and other gastrointestinal disorders are associated with increased numbers of EC
      cells and 5-HT availability. Our aim was to determine whether proliferation of EC
      cells contributed to the hyperplasia associated with intestinal inflammation.
      Ileitis was induced in guinea-pigs by intraluminal injection of 2,4,6
      trinitrobenzene sulphonic acid (TNBS). A single pulse of 5-bromo-2'-deoxyuridine
      (BrdU) was injected 1 or 24 h before the collection of tissue, 6 or 7 days after
      TNBS treatment. In the controls, the labelling index (percentage of BrdU-labelled
      EC cells) was less than 1%. Despite a significant increase in EC cells in the
      inflamed ileum, the labelling index was similar in the TNBS-treated animals to
      that of controls. An increased occurrence of EC cells in the BrdU-labelled zone
      accounted for the increase in EC cells in the inflamed ileum. Goblet cell numbers
      were also significantly increased in the inflamed ileum, indicating that cell
      hyperplasia was not limited to the enteroendocrine cell lineage. This study
      demonstrates that a small portion of EC cells retain some proliferative capacity;
      however, hyperplasia associated with ileitis is not attributable to the increased
      proliferation of EC cells and is not limited to one cell lineage. Therefore, EC
      cell hyperplasia most probably occurs at the level of the stem cell or
      recruitment from the progenitor pool.

PMID- 17508221
TI  - Distribution of vesicular glutamate transporter 1 (VGLUT1) in the mouse
      esophagus.
AB  - In rat and mouse esophagus, vesicular glutamate transporter 2 (VGLUT2) has been
      demonstrated to identify vagal intraganglionic laminar endings (IGLEs); this has
      recently also been shown for VGLUT1 in rat esophagus. In this study, we have
      investigated the distribution of VGLUT1 in the mouse esophagus and compared these
      results with the recently published data from the rat esophagus. Unexpectedly, we
      have discovered that VGLUT1 mostly fails to identify IGLEs in the mouse
      esophagus. This is surprising, since the distribution of VGLUT2 shows comparable
      results in both species. Confocal imaging has revealed substantial colocalization
      of VGLUT1 immunoreactivity (-ir) with cholinergic and nitrergic/peptidergic
      markers within the myenteric neuropil and in both cholinergic and nitrergic
      myenteric neuronal cell bodies. VGLUT1 and cholinergic markers have also been
      colocalized in fibers of the muscularis mucosae, whereas VGLUT1 and nitrergic
      markers have never been colocalized in fibers of the muscularis mucosae, although
      this does occur in fibers of the muscularis running to motor endplates. Thus,
      VGLUT1 is contained in the nitrergic innervation of mouse esophageal motor
      endplates, another difference from the rat esophagus. VGLUT1-ir is therefore
      present in extrinsic and intrinsic innervation of the mouse esophagus, but the
      significant differences from the rat indicate species variations concerning the
      distribution of VGLUTs in the peripheral nervous system.

PMID- 17508222
TI  - A male infant with bilateral upper urinary tract dilatation and recurrent
      infection: question.

PMID- 17508223
TI  - A male infant with bilateral upper urinary tract dilatation and recurrent
      infection: answer.

PMID- 17508224
TI  - Linguistic dimensions of weather and climate perception.
AB  - The purpose of this research was to explore the latent dimensions that underlie
      people's use of adjectives that can describe weather and climate conditions. A
      sample of 1,011 university undergraduate students residing the southeastern
      United States evaluated the weather and climate of that region using 143 English
      language adjectives. Data were collected over a two-year period during various
      weather and seasonally related climatic conditions. Polychoric correlations among
      the adjective ratings were calculated; the matrix of correlations was factor
      analyzed. Twelve underlying factors related to weather and climate perceptions
      were observed: 1. threatening, severe, violent, 2. dismal, drab, dark, 3. cold
      and wintry, 4. hot and summery, 5. tranquil and pleasant, 6. stormy and wet, 7.
      bright and clear, 8. blowing and blustery, 9. damp and moist, 10. cloudy and
      cool, 11. predictable and unchanging, and 12. hazy and dusty. A second-order
      factor analysis revealed two factors pertaining to weather valence: 1. bad or
      extreme and 2. good or routine conditions. The study results were noteworthy in
      revealing some of the basic linguistic dimensions along which people perceive and
      experience weather and climate at the current time in the southeastern United
      States. The study also represents the use of a new technique for
      biometeorologists to use in assessing climate perceptions in culturally and
      climatically diverse regions.

PMID- 17508226
TI  - The impact of generic substitution on price competition in Finland.
AB  - Generic substitution by pharmacists was introduced in April 2003 in Finnish
      pharmaceutical markets. This article examines the impact of generic substitution
      on price development. This study examined all of the 2,100 substitutable drugs in
      Finland. The impact of generic substitution on price competition was significant.
      The average price of substitutable drugs decreased by more than 10%. However, the
      price development was uneven; some prices increased whereas others decreased by
      more than 50%. The most important factors that influenced the price development
      were the number of competitors, whether the drug was originator or generic and
      the width of the price band.

PMID- 17508225
TI  - The implications of ISAT and ISUIA for the management of cerebral aneurysms
      during pregnancy.
AB  - Both the International Subarachnoid Aneurysm Trial (ISAT) and the International
      Study on Unruptured Intracranial Aneurysms (ISUIA) have been widely extrapolated
      to influence the management of actual or anticipated aneurysmal subarachnoid
      hemorrhage (SAH). However, it remains possible that sub-groups exist for which
      such extrapolation might subsequently prove premature. In this review, we discuss
      the implications that such extrapolation may potentially have for one such SAH
      sub-group: the clinically rare scenario of SAH in pregnancy.

PMID- 17508227
TI  - Thermal responses for men with different fat compositions during immersion in
      cold water at two depths: prediction versus observation.
AB  - A cold thermoregulatory model (CTM) was applied to data from partially immersed
      subjects divided into normal (NF) or low fat (LF) groups in order to validate CTM
      during immersion at two depths and to examine mechanisms underlying the
      individual differences. CTM defines thermal characteristics, e.g. surface area
      and maximal shivering intensity, using height, weight, fat %, age and VO(2max).
      Ten clothed subjects, 5 NF (15-19%) and 5 LF (8.1-14.7%), were immersed in both
      10 and 15 degrees C water at chest (CH) and waist (WA) level. Environmental and
      clothing inputs for CTM were weighted to adjust for the ratio of skin surface
      area covered by either air or water at various immersion depths. Predicted core
      temperature (Tc) responses for each individual trial were compared with measured
      data. There were no significant differences (P > 0.05) between measured Tc and
      predicted Tc for NF at all four conditions. In contrast, for the LF group, the
      predicted Tc responses were all higher than measured (P < 0.05). However,
      predicted Tc agreed closer with measured Tc for LF when leg muscle blood flow was
      increased in the simulation. This suggests that blood flow may contribute to the
      rapid decline in Tc observed in LF and its variance may cause in part the
      individual differences in Tc responses. CTM predicts Tc responses to immersion at
      various depths with acceptable accuracy for NF individuals in this study and can
      be adapted to non-uniform environments.

PMID- 17508228
TI  - Electromyogram and perceived fatigue changes in the trapezius muscle during
      typewriting and recovery.
AB  - The purpose of the present study was to investigate the development and recovery
      of muscle fatigue in the upper trapezius muscle by analyzing electromyographic
      signals. Six male subjects performed a simulated typewriting task for four 25-min
      sessions. During fatigue and the following rest periods, subjective fatigue and
      surface electromyography (EMG) from the trapezius muscle during isometric
      contraction at 30% maximum voluntary contraction (MVC) were periodically measured
      in the interval. We detected a significant decrease in muscle fiber conduction
      velocity (MFCV) (P = 0.008) and median frequency (MDF) (P = 0.026) as well as an
      increase in root mean square (RMS) (P = 0.039) and subjective fatigue (P =
      0.0004) during the fatigue period. During the recovery period, subjective fatigue
      decreased drastically and significantly (P = 0.0004), however, the EMG parameters
      did not recover completely. Thus, physiological muscle fatigue in the trapezius
      developed in accordance with subjective muscle fatigue during typewriting. On the
      other hand, differences between the physiological and subjective parameters were
      found during recovery. Further studies should be necessary to reveal the
      discrepancy could be a major factor of a transition from temporal phenomena to
      serious chronic muscle fatigue and to identify the necessity of some guidelines
      to prevent VDT work-related chronic muscle fatigue in the trapezius.

PMID- 17508229
TI  - Sac hygroma after endovascular treatment of abdominal aortic aneurysm.

PMID- 17508230
TI  - Evaluation of left atrial myxoma by dual-source CT.

PMID- 17508231
TI  - A technical tip to aid successful placement of a colonic stent.

PMID- 17508232
TI  - Polyarteritis nodosa: MDCT as a "one-stop shop" modality for whole-body arterial
      evaluation.
AB  - Polyarteritis nodosa is a rare disease, which is characterized by aneurysm
      formation and occlusion in the arteries of multiple systems. Due to its extensive
      involvement, whole-body evaluation is necessary for diagnosis and treatment
      monitoring. We report a case of polyarteritis nodosa using multidetector-row
      computed tomography (MDCT) as a "one-stop shop" modality for whole-body arterial
      evaluation. With precise protocol design, MDCT can be used as a reliable
      noninvasive modality providing comprehensive whole-body arterial evaluation.

PMID- 17508233
TI  - Stretched platinum coil during cerebral aneurysm embolization after direct
      carotid puncture: two case reports.
AB  - We describe two cases of coil unraveling that occurred during cerebral aneurysm
      embolization after direct carotid puncture. The unraveled coil was stretched and
      buried in the subcutaneous part of the neck. No immediate or long-term
      complication was observed.

PMID- 17508234
TI  - Embolization of a giant hepatic hemangioma prior to urgent liver resection. Case
      report and review of the literature.

PMID- 17508235
TI  - Use of 120 kilovolt tube potential for digital subtraction angiography and
      fluoroscopy in an image-intensifier angiographic system: decrease of skin dose in
      transarterial chemoembolization therapy for hepatocellular carcinoma.
AB  - In an image-intensifier angiographic system, the tube potential is commonly
      regulated in ranges from 75 to 90 kV for digital subtraction angiography (DSA)
      and fluoroscopy in transarterial chemoembolization therapy (TACE) for
      hepatocellular carcinoma. The purpose of this study was to investigate whether or
      not a 120-kV tube potential could be used for DSA and fluoroscopy in TACE to
      decrease the skin dose. Forty-three patients administered TACE were randomly
      allocated into two groups: TACE was performed using standard-kilovoltage (75- to
      90-kV) DSA and fluoroscopy modes (group A; n = 20) or using high-kilovoltage (120
      kV) modes (group B; n = 23). The peak skin dose was compared between the groups.
      One case in group A was excluded from the study because the HCC nodule was not
      depicted on DSA. The peak skin dose (mGy) for group A was 383.6 +/- 176.5 and
      that for group B was 265.1 +/- 145.1. The peak skin dose was decreased by 31% in
      the 120-kV mode, a statistically significant difference (t-test, p = 0.022). We
      conclude that the use of 120 kV tube potential for DSA and fluoroscopy may be one
      option for performing TACE while decreasing the skin dose.

PMID- 17508236
TI  - ePTFE/FEP-covered metallic stents for palliation of malignant biliary disease:
      can tumor ingrowth be prevented?
AB  - PURPOSE: To determine the application and clinical effectiveness of ePTFE/FEP
      covered metallic stents for palliation of malignant biliary disease, and to
      evaluate the efficiency of stent coverage in preventing tumor ingrowth. METHODS:
      During a 3-year period, 36 patients with malignant obstructive jaundice were
      treated with ePTFE/FEP-covered stents, with or without proximal side holes. The
      stricture was located in the lower common bile duct (CBD) in 18 cases, the upper
      CBD in 9, the lower common hepatic duct (CHD) in 6, and the upper CHD in 3
      patients. RESULTS: Thirty-seven covered stents were percutaneously implanted. The
      technical success rate was 97%. Reintervention was required in 6 cases. The 30
      day mortality rate was 40%, not procedure-related. Mean survival was 128 days.
      Primary patency rates were 100%, 55.5%, and 25% at 3, 6, and 12 months,
      respectively, while the assisted patency rate was 100% at 12 months. Stents
      without side holes had higher primary patency rates compared with those with side
      holes, where occlusion was always due to tumor ingrowth. Tumor ingrowth did not
      occur in the completely covered stents. No stent dysfunction due to sludge
      incrustation was found. Complications were 1 case of arterial laceration that
      occurred during percutaneous transhepatic cholangiography, and a subcapsular
      hematoma and 1 case of bile peritonitis, that both occurred during primary
      stenting. No complications followed the secondary stenting technique. CONCLUSION:
      ePTFE/FEP-covered metallic stents are safe and effective for palliation of
      malignant biliary disease. The presence of the ePTFE/FEP coating is likely to
      prevent from tumor ingrowth.

PMID- 17508237
TI  - Endovascular treatment of anastomotic pseudoaneurysms after aorto-iliac surgical
      reconstruction.
AB  - PURPOSE: To assess the effectiveness of endovascular treatment of anastomotic
      pseudoaneurysms (APAs) following aorto-iliac surgical reconstruction. MATERIALS:
      We retrospectively evaluated 21 men who, between July 2000 and March 2006, were
      observed with 30 APAs, 13 to the proximal anastomosis and 17 to the distal
      anastomosis. The patients had had previous aorto-iliac reconstructive surgery
      with a bypass due to aneurysm (15/21) or obstructive disease (6/21). The
      following devices were used: 12 bifurcated endoprostheses, 2 aorto-monoiliac, 4
      aortic extenders, 1 stent-graft leg, and 2 covered stents. Follow-up was
      performed with CT angiography at 1, 3, and 6 months after the procedure and
      yearly thereafter. RESULTS: Immediate technical success was 100%. No
      periprocedural complications occurred. Four patients died during follow-up from
      causes not related to APA, and 1 (treated for prosthetic-enteric fistula) from
      sepsis 3 months after the procedure. During a mean follow-up of 19.7 months
      (range 1-72 months), 2 of 21 occlusions of stent-graft legs occurred 3 and 24
      months after the procedure (treated with thrombolysis and percutaneous
      transluminal angioplasty and femorofemoral bypass, respectively) and 1 type I
      endoleak. Primary clinical success rate was 81% and secondary clinical success
      was 91%. CONCLUSION: Endovascular treatment is a valid alternative to open
      surgery and can be proposed as the treatment of choice for APAs, especially in
      patients who are a high surgical risk. Further studies with larger series and
      longer follow-up are necessary to confirm the long-term effectiveness of this
      approach.

PMID- 17508238
TI  - Initial experience with the resonance metallic stent for antegrade ureteric
      stenting.
AB  - BACKGROUND AND PURPOSE: We describe our initial experience with a new metallic
      ureteric stent which has been designed to provide long-term urinary drainage in
      patients with malignant ureteric strictures. The aim is to achieve longer primary
      patency rates than conventional polyurethane ureteric stents, where encrustation
      and compression by malignant masses limit primary patency. The Resonance metallic
      double-pigtail ureteric stent (Cook, Ireland) is constructed from coiled wire
      spirals of a corrosion-resistant alloy designed to minimize tissue in-growth and
      resist encrustation, and the manufacturer recommends interval stent change at 12
      months. METHODS: Seventeen Resonance stents were inserted via an antegrade
      approach into 15 patients between December 2004 and March 2006. The causes of
      ureteric obstruction were malignancies of the bladder (n = 4), colon (n = 3),
      gynecologic (n = 5), and others (n = 3). RESULTS: One patient had the stent
      changed after 12 months, and 3 patients had their stents changed at 6 months.
      These stents were draining adequately with minimal encrustation. Four patients
      are still alive with functioning stents in situ for 2-10 months. Seven patients
      died with functioning stents in place (follow-up periods of 1 week to 8 months).
      Three stents failed from the outset due to bulky pelvic malignancy resulting in
      high intravesical pressure, as occurs with conventional plastic stents.
      CONCLUSION: Our initial experience with the Resonance metallic ureteric stent
      indicates that it may provide adequate long-term urinary drainage (up to 12
      months) in patients with malignant ureteric obstruction but without significantly
      bulky pelvic disease. This obviates the need for regular stent changes and would
      offer significant benefit for these patients with limited life expectancy.

PMID- 17508240
TI  - Transhepatic approach for percutaneous computed-tomography-guided radiofrequency
      ablation of renal cell carcinoma.
AB  - We performed percutaneously radiofrequency (RF) ablation of 5 renal cell
      carcinomas (mean diameter 26 +/- 15 mm) with computed-tomography (CT)
      fluoroscopic guidance using the transhepatic route. The RF electrode was
      successfully advanced into all tumors. RF ablation caused one minor complication
      (small asymptomatic perirenal hematoma); no major complications occurred. The
      follow-up contrast-enhanced CT images showed no local tumor progression of any
      tumors in a median period of 10 months (range 3-14 months). In conclusion, it
      seems that this transhepatic approach is safe and can be an alternative method
      for electrode insertion during RF ablation of selected renal tumors.

PMID- 17508239
TI  - Similar success rates with bivalirudin and unfractionated heparin in bare-metal
      stent implantation.
AB  - BACKGROUND: Unfractionated heparin (UFH) is the traditional agent utilized during
      percutaneous peripheral interventions (PPIs) despite its well-known limitations.
      Bivalirudin, a thrombin-specific anticoagulant, overcomes many of the limitations
      of UFH and has consistently demonstrated comparable efficacy with significantly
      fewer bleeding complications. The purpose of this study was to compare procedural
      success in patients undergoing bare-metal stent implantation for atherosclerotic
      blockage of the renal, iliac, and femoral arteries and receiving either
      bivalirudin (0.75 mg/kg bolus/1.75 mg/kg/hr infusion) or UFH (50-70 U/kg/hr
      bolus) as the primary anticoagulant. METHODS: This study was an open-label,
      nonrandomized retrospective registry with the primary endpoint of procedural
      success. Secondary endpoints included incidence of: death, myocardial infarction
      (MI), urgent revascularization, amputation, and major and minor bleeding.
      RESULTS: One hundred and five consecutive patients were enrolled (bivalirudin =
      53; heparin = 52). Baseline demographics were comparable between groups. Patients
      were pretreated with clopidogrel (approx. 71%) and aspirin (approx. 79%).
      Procedural success was achieved in 97% and 96% of patients in the bivalirudin-
      and heparin-treated groups, respectively. Event rates were low and similar
      between groups. CONCLUSION: Bivalirudin maintained an equal rate of procedural
      success in this cohort without sacrificing patient safety. Results of this study
      add to the growing body of evidence supporting the safety and efficacy of
      bivalirudin as a possible substitute for UFH in anticoagulation during peripheral
      vascular bare-metal stent implantation.

PMID- 17508241
TI  - Interventional management of renal bleeding after partial nephrectomy.
AB  - OBJECTIVE: Partial nephrectomy (PN) has emerged as a serious alternative to
      nephrectomy in oncologic therapy of renal tumours. While complications are rare
      in general, renal hemorrhage may occur und necessitate angiographic embolization.
      In this retrospective study, we evaluate the clinical, imaging and procedural
      findings of seven interventions in five patients with renal hemorrhage after PN.
      In four out of five patients (80%) the bleeding could be treated successfully by
      embolotherapy. CONCLUSION: Angiographic embolization in patients with renal
      hemorrhage after PN is feasible and has a high success rate. The procedure might
      facilitate avoidance of nephrectomy.

PMID- 17508242
TI  - Transarterial chemoembolization (TACE) for inoperable intrahepatic
      cholangiocarcinoma.
AB  - The aim of this retrospective study was to determine the safety and efficacy of
      chemoembolization (TACE) as palliative treatment for patients with unresectable
      intrahepatic cholangiocarcinoma (CCA) and to compare the results with those in
      the literature. Fifteen patients with histology-proven CCA (5 men, 10 women) had
      received palliative treatment with TACE over a 6-year period. The treatment
      protocol comprised repeated TACE at a minimum of 8-week intervals. TACE was
      performed with a mixture of 10 ml Lipiodol and 10 mg mitomycin C injected into
      the tumor-supplying vessels. Follow-up investigations after 8-10 weeks comprised
      contrast-enhanced multislice spiral CT and laboratory control. Statistical
      evaluation included survival analysis using the Kaplan-Meier method. During the
      investigation period 58 TACEs (3.9 +/- 3.8; 1-15) were performed in 15 patients.
      Mean tumor size was 10.8 +/- 4.6 cm (range, 2.0-18.0 cm). Unifocal tumor disease
      was diagnosed in eight patients, and multifocal disease in seven. Mean survival
      was 21.1 months (95% CI, 9.4-32.5 months). At the end of the investigation period
      3 patients are still alive, and 12 patients have died. The 1-, 2-, and 3-year
      survival rate was 51.3%, 27.5%, and 27.5% respectively. According to RECIST
      criteria interim best response to therapy was stable disease in 9 of 15 patients,
      a partial response in 1 of 15 patients, and tumor progression in 4 of 15
      patients. No deaths and no acute liver failure occurred under TACE therapy. Major
      complications were observed in two patients, comprising anaphylactic shock owing
      to contrast medium administration in one and gastric ulceration due to lipiodol
      displacement in the second patient. These results demonstrate that TACE is a safe
      procedure with a moderate number of complications for patients suffering from
      inoperable CCA. According to recently published data on i.v. chemotherapy we
      suggest that TACE might be able to prolong survival in selected patients who
      would succumb under other palliative treatment modalities.

PMID- 17508243
TI  - Percutaneous therapy of ureteral obstructions and leak after renal
      transplantation: long-term results.
AB  - The purpose of this study was to evaluate the long-term outcome of percutaneous
      therapy of ureteral complications after renal transplantation. Between January
      2000 and June 2006 we percutaneously treated 26 renal transplant patients with
      ureteral obstruction (n=19) and leak (n=7). Obstructions were classified as early
      (<2 months after transplantation) or late (>2 months). Patients with leak were
      treated with nephro-ureteral catheter placement and subsequent double-J stenting.
      Balloon dilatation, stent placement, and basket extraction were used to treat
      ureteral obstructions. Patients were followed with ultrasonography. No major
      procedure-related complication occurred. The mean follow-up time was 34.3 months
      (range: 6 to 74 months). Initial clinical success was achieved in all 19 patients
      with obstruction and 6 of 7 patients with leak. Four of 9 early obstructions and
      4 of 10 late obstructions recurred during the follow-up. All recurrences were
      initially managed again with percutaneous methods, including cutting balloon
      technique and metallic stent placement. Although there was no recurrence in
      patients with successfully treated leak, stricture was seen at the previous leak
      site in two patients. These strictures were also successfully managed
      percutaneously. We conclude that in the treatment of ureteral obstruction and
      leak following renal transplantation, percutaneous therapy is an effective
      alternative to surgery. However, further interventions are usually needed to
      maintain long-term patency.

PMID- 17508244
TI  - Endovascular repair of localized pathological lesions of the descending thoracic
      aorta: midterm results.
AB  - The endoluminal stent-graft represents an attractive and a less invasive
      technique for treatment of various diseases of the descending thoracic aorta. The
      purpose of this study was to evaluate the Talent endovascular stent-graft for the
      treatment of various localized diseases of the descending thoracic aorta. Over a
      3-year period, Talent thoracic endografts were placed in 40 patients with a high
      surgical risk, presenting a localized lesion of the descending thoracic aorta:
      degenerative aneurysm (n = 13), acute traumatic rupture (n = 11), acute Stanford
      type B aortic dissection (n = 6), false aneurysm (n = 7), and penetrating
      atherosclerotic ulcer (n = 3). Fifteen patients (37.5%) were treated as
      emergencies. The feasibility of endovascular treatment and sizing of the aorta
      and stent-grafts were determined preoperatively by magnetic resonance angiography
      (MRA) and intraoperative angiography. Immediate and mid-term technical and
      clinical success was assessed by clinical and MRA follow-up. Endovascular
      treatment was completed successfully in all 40 patients, with no conversion to
      open repair or intraoperative mortality. The mean operative time was 37.5 +/- 7
      min. The overall 30-day mortality rate was 10% (n = 4), all in emergency cases,
      for causes not related to the endograft. The primary technical success was 92.5%.
      The mean follow-up period was 15 +/- 5 months. The survival rate was 95% (n =
      35). Diminution of the aneurismal size was observed in 47.5% (n = 19). We
      conclude that endovascular treatment of the various localized diseases of the
      descending thoracic aorta is a promising, feasible, alternative technique to open
      surgery in well-selected patients.

PMID- 17508246
TI  - Femoral artery thrombosis following percutaneous treatment with thrombin
      injection of a femoral artery pseudoaneurysm: a case report.

PMID- 17508245
TI  - Lymphangiography: forgotten tool or rising star in the diagnosis and therapy of
      postoperative lymphatic vessel leakage.
AB  - Since the advent of computed tomography, numbers and expertise in
      Lymphangiography (LAG) have markedly dropped. The intention of our study was to
      demonstrate the persisting diagnostic and therapeutic impact of LAG on the
      postoperative patient with known or suspected lymphatic vessel leakage. Between
      May 1, 1999, and April 30, 2006, we investigated pedal lipiodol-LAGs (18
      monopedal, 2 bipedal) on 22 patients (16 male, 6 female) with known or suspected
      postoperative chylothorax, chylaskos, lymphocele, or lymphatic fistula. Ages
      varied from 26 to 81 years. The spectrum of operative procedures was broad: 6
      thoracic, 5 abdominal, and 11 peripheral operations were performed. In 20
      patients who underwent mono- or bipedal LAG for lymphatic vessel injury, we were
      able to demonstrate the specific site of leakage in 15 cases (75%) and found
      signs of extravasation in 5 patients (25%). Furthermore, in 11 patients (55%) we
      were able to avoid surgery because of closure of the leak after LAG. As the
      conservative therapeutic approach usually takes 2-3 weeks to reveal its
      therapeutic effects, 73.3% (11/15) of the patients who were not reoperated before
      this hallmark was passed did not need any further operation. Our study clearly
      demonstrates that even in the decades of modern cross-sectional imaging, classic
      LAG is a powerful and highly reliable tool to visualize and even assist occlusion
      of the postoperatively damaged lymphatic vessel and may thereby avoid the need
      for reoperation.

PMID- 17508247
TI  - Neurological complications following endoluminal repair of thoracic aortic
      disease.
AB  - Open surgery for thoracic aortic disease is associated with significant morbidity
      and the reported rates for paraplegia and stroke are 3%-19% and 6%-11%,
      respectively. Spinal cord ischemia and stroke have also been reported following
      endoluminal repair. This study reviews the incidence of paraplegia and stroke in
      a series of 186 patients treated with thoracic stent grafts. From July 1997 to
      September 2006, 186 patients (125 men) underwent endoluminal repair of thoracic
      aortic pathology. Mean age was 71 years (range, 17-90 years). One hundred twenty
      eight patients were treated electively and 58 patients had urgent procedures.
      Anesthesia was epidural in 131, general in 50, and local in 5 patients. Seven
      patients developed paraplegia (3.8%; two urgent and five elective). All occurred
      in-hospital apart from one associated with severe hypotension after a myocardial
      infarction at 3 weeks. Four of these recovered with cerebrospinal fluid (CSF)
      drainage. One patient with paraplegia died and two had permanent neurological
      deficit. The rate of permanent paraplegia and death was 1.6%. There were seven
      strokes (3.8%; four urgent and three elective). Three patients made a complete
      recovery, one had permanent expressive dysphasia, and three died. The rate of
      permanent stroke and death was 2.1%. Endoluminal treatment of thoracic aortic
      disease is an attractive alternative to open surgery; however, there is still a
      risk of paraplegia and stroke. Permanent neurological deficits and death occurred
      in 3.7% of the patients in this series. We conclude that prompt recognition of
      paraplegia and immediate insertion of a CSF drain can be an effective way of
      recovering spinal cord function and improving the prognosis.

PMID- 17508249
TI  - Validating a predictive model for presence of additional disease in the non
      sentinel lymph nodes of a woman with sentinel node positive breast cancer.

PMID- 17508248
TI  - Endovascular PTFE-covered stent for treatment of an external iliac artery
      pseudoaneurysm in the presence of chronic infection.
AB  - A 75-year-old woman with an external iliac artery pseudoaneurysm, thought to have
      resulted from a chronic loosening and infection of a total hip replacement, was
      successfully treated by placement of a covered endoluminal stent.

PMID- 17508250
TI  - Carcinoma metastatic to cervical lymph nodes from an occult primary tumor: the
      outcome after combined-modality therapy.
AB  - BACKGROUND: The aim of this retrospective analysis was to analyze the results of
      treatment of patients with cervical node metastases from carcinoma of occult
      primary with a policy including neck dissection and postoperative comprehensive
      radiotherapy. METHODS: Ninety patients were treated with curative intent from
      1990 to 2002. RESULTS: The actuarial rate of neck disease control was 68.8% at 5
      years (95% confidence interval [CI], 58.9%-78.7%). On multivariate analysis, the
      rate of neck disease control was significantly related to lymph nodal metastatic
      level (P = .006). The actuarial rate of developing head and neck primary tumors
      at 5 years was 8.9% (95% CI, 2.6%-15.2%). The 5-year actuarial rate of distant
      metastases was 19.1% (95% CI, 9.4%-28.9%). In multivariate analysis, a
      statistically significant difference in the rate of distant metastasis was
      obtained when patients were stratified according to the level of nodal
      involvement (P = .01) and the presence of extracapsular extension (P = .013). At
      the time of analysis, 50 of the 90 patients were alive. A total of 32 (35.6%) had
      died from causes related to their primary disease. Actuarial disease-specific
      survival at 2 and 5 years was 73.6% (95% CI, 64.3%-82.9%) and 62.8% (95% CI,
      51.9%-73.7%), respectively. In multivariate analysis, a statistically significant
      difference in disease-specific survival was obtained when patients were
      stratified according to the level of nodal involvement and the presence of
      extracapsular extension. CONCLUSIONS: Our study seems to support the use of
      combined-modality therapy in patients with neck metastases from carcinoma of
      occult primary. However, in the absence of randomized trials, comprehensive
      irradiation cannot be routinely advised.

PMID- 17508251
TI  - A phase II trial of image-guided radiofrequency ablation of small invasive breast
      carcinomas: use of saline-cooled tip electrode.
AB  - BACKGROUND: Local ablative therapy of breast cancer represents the next frontier
      in the evolution of minimally-invasive breast conservation therapy. We performed
      this Phase II trial to determine the efficacy and safety of Radiofrequency (RF)
      ablation of small invasive breast carcinomas. METHODS: Seventeen patients with
      biopsy-proven invasive breast cancer, < or = 1.5 cm in diameter were enrolled in
      this trial. Under ultrasound guidance, the tumor and a 5 mm margin of surrounding
      breast tissue were ablated with saline-cooled RF electrode followed by surgical
      resection. Pathologic and immunohistochemical stains were performed to assess
      tumor viability. We examined whether loss of ER, PR receptor and pancytokeratin
      expression following RF ablation would correlate with non-viability. RESULTS:
      Fifteen patients completed the treatment. The mean tumor size was 1.28 cm. The
      mean ablation time was 21 minutes using a mean power of 35.5 watts. During
      ablation, the tumors became progressively echogenic that corresponded with the
      region of severe electrocautery injury at pathological examination. Of the 15
      treated patients, NADPH viability staining was available for 14 patients and in
      13 (92.8%), there was no evidence of viable malignant cells. ER, PR expression
      and pancytokeratin immunohistochemistry analysis were unreliable surrogates for
      determining non-viability. Following RF ablation, 2 patients developed skin
      puckering. CONCLUSIONS: RF ablation is a promising minimally invasive treatment
      of small breast carcinomas, as it can achieve effective cell killing with a low
      complication rate. Further research is necessary to optimize this image-guided
      technique and evaluate its future role as the sole local therapy.

PMID- 17508252
TI  - Distal pancreatectomy for chronic pancreatitis: risk factors for postoperative
      pancreatic fistula.
AB  - One of the most common complications after distal pancreatectomy is a fistula
      from the pancreatic remnant. Factors influencing the development of a pancreatic
      fistula after distal pancreatectomy have not been clearly elucidated. The records
      of 91 patients who underwent distal pancreatectomy for chronic pancreatitis
      between 1995 and 2003 were retrospectively reviewed and analyzed. Average daily
      volume and amylase concentration between postoperative days 2 and 20 from drains
      located at the pancreatic resection site were compared to clinical variables. Out
      of 137 pre- and intraoperative clinical variables, multivariate analysis showed
      serum creatinine (t = 3.05, p = 0.004), history of intraabdominal operation (t = 
      2.68, p = 0.01), right-sided pancreatic duct dilation (t = 2.65, p = 0.01),
      synchronous cholecystectomy (t = 2.53, p = 0.02), and serum albumin (t = -2.19, p
      = 0.04) to be independently associated with drain volume. Drain amylase
      concentration was linked to serum creatinine (t = 8.55, p < 0.001), blood urea
      nitrogen (t = -3.43, p = .001), preoperative parenteral nutrition (t = 2.56, p =
      .01), and serum alkaline phosphatase (t = 2.51, p = 0.01). There was no
      correlation between the degree of fibrosis and drain output. Technique of
      pancreatic transection and presence of suture closure of the pancreatic duct did
      not affect drain output. In conclusion, the amount and amylase concentration of
      postsurgical drainage after distal pancreatectomy for chronic pancreatitis is
      dependent on markers of renal dysfunction, malnutrition, biliary disease, and
      possibly inflammation. These factors, if medically reversible, should be
      addressed in patients who are candidates for distal pancreatectomy for chronic
      pancreatitis.

PMID- 17508253
TI  - Development of a simple model of extrinsic denervation of the small bowel in
      mouse.
AB  - Small bowel transplantation (SBT) is associated with poorly understood enteric
      dysfunction. The study of SBT in mice is hindered by the technical difficulty of
      orthotopic SBT in the mouse. Our aim was to develop an easy preparation of
      extrinsic denervation of the entire jejunoileum in mice as a model of orthotopic
      SBT. All neurolymphatic tissues accompanying the superior mesenteric artery (SMA)
      and vein (SMV) were ligated just distal to the middle colic vessels. The SMA and
      SMV were then stripped of investing adventitia, and the mesentery to jejunum and
      colon were transected radially. Jejunum and colon were not transected and
      reanastomosed. To confirm extrinsic denervation 1, 3, and 6 months later,
      segments of small bowel were stained for protein gene product 9.5 (PGP9.5) and
      tyrosine hydroxylase (TH). Tyrosine hydroxylase immunoreactive intensity was then
      quantified using a semiquantitative analysis. Immunohistochemical fluorescence
      showed persistence of PGP9.5 immunoreactivity confirming enteric nerves in
      jejunoileum; however, there was no TH immunoreactivity in jejunoileum in
      denervated mice despite the expected preservation of TH immunoreactivity in the
      still-innervated duodenum at 1 month. At 3 months, sparse immunoreactivity for TH
      was present, and by 6 months, reinnervation of TH-containing nerves appeared
      similar to controls. Quantification of intensity at each time-point further
      confirmed this trend. This technique in the mouse accomplishes a complete
      extrinsic denervation of jejunoileum early postoperatively (1 and 3 months);
      reinnervation occurs by 6 months. This is an easily learned murine model of
      orthotopic SBT.

PMID- 17508254
TI  - Pseudomyxoma peritonei presenting with femoral hernias and peritonitis.
AB  - Pseudomyxoma peritonei is a rare disease characterized by intraperitoneal
      accumulation of mucinous ascites produced by neoplastic cells, which mostly
      originate from an appendiceal adenoma. The clinical presentation of the disease
      varies, and preoperative diagnosis is often difficult. This report describes a 76
      year-old female patient with pseudomyxoma peritonei who presented with lower
      abdominal pain and bilateral femoral masses. Computed tomography revealed
      bilateral femoral hernias and fluid collection in the peritoneal cavity.
      Laparotomy was performed, during which we found extensive diffuse gelatinous
      material mixed with purulent ascites, and the diagnosis of pseudomyxoma peritonei
      was confirmed. The disease is rarely associated with femoral hernias or
      peritonitis. Its clinical presentation, including the characteristic findings on
      computed tomography, and surgical management are briefly reviewed.

PMID- 17508255
TI  - Inferior vena cava stenting: a safe and effective treatment for intractable
      ascites in patients with polycystic liver disease.
AB  - We performed a retrospective study of seven patients with polycystic liver
      disease who underwent stenting of the inferior vena cava for intractable ascites.
      All patients had symptomatic ascites and inferior vena cava stenosis demonstrable
      by venography. The mean pressure gradient across the inferior vena cava stenosis
      before stenting was 14.5 mm Hg (range 6-25 mm Hg) and significantly decreased to
      a mean pressure gradient of 2.8 mm Hg (range 0-6 mm Hg, p = 0.008) after
      stenting. Two patients also had stenting of hepatic venous stenoses after
      unsuccessful inferior vena cava stenting. After a mean follow-up of 12.2 months
      (range 0.5-39.1 months), five of the seven patients have had maintained clinical
      improvement, defined as decreased symptoms, diuretic requirements, and frequency
      of paracentesis. Four patients have required no further intervention. The other
      patient was lost in follow-up. Patients with clinical improvement had an overall
      larger mean pressure gradient before stenting (19.2 vs. 9.8 mm Hg) and a larger
      Delta pressure gradient (15.8 vs. 7.8 mm Hg) compared to those in whom stenting
      was unsuccessful. These results suggest inferior vena cava stenting is safe and
      effective and should be considered as a first-line intervention in the treatment
      of medically intractable ascites in select patients with polycystic liver
      disease.

PMID- 17508256
TI  - A curative resection improves the postoperative survival rate even in patients
      with advanced gallbladder carcinoma.
AB  - The aim of this study was to evaluate the results of our series of 90 operations
      for gallbladder carcinoma according to the Japanese Society of Biliary Surgery
      (JSBS) classification system and to clarify the appropriate surgical strategy for
      advanced gallbladder carcinoma based on the depth of primary tumor invasion and
      lymph node metastasis. Generally, only a surgical resection can achieve a
      prognostic improvement of the advanced gallbladder carcinoma. The survival of
      patients with this neoplasm depends strictly on the depth of histological primary
      tumor invasion and lymph node metastasis. A retrospective analysis was conducted
      on 90 patients from 1990 to 2004 who underwent a surgical resection of
      gallbladder carcinoma. The factors influencing survival were examined. Thirty
      nine patients with palliative treatment (not resected cases), which was diagnosed
      as T3 or T4 by preoperative imagings, were also included in this study. The
      significance of the variables for survival was examined by the Kaplan-Meier
      method and the log-rank test followed by multivariate analyses using Cox's
      proportional hazard model. Portal invasion, lymph node metastasis, the surgical
      margin (+ vs. -) and the final curability (fCurA, B vs. C) were all found to be
      independent prognostic factors in the multivariate analysis. In pT2 gallbladder
      carcinoma, a better survival was achieved in an aggressive surgical approach, in
      order of a S4a+S5 hepatic resection, an extended cholecystectomy and a
      cholecystectomy. In pT3 and pT4, although radical extended surgery did not
      provide the opportunity for good survival even after lobectomy of the liver, the
      survival of patients with curative surgery was statistically better than in those
      without curative surgery. In addition, the nodal involvement of pN1 to pN2 was
      better than that with pN3. A S4a+S5 hepatectomy, therefore, appears to be
      adequate for the treatment of pT2 gallbladder carcinoma. Even in patients with
      pT3 and pT4 gallbladder carcinoma, long-term survival can be expected by an
      operation with a tumor-free surgical margin. The role of radical surgery,
      however, is considered to be limited in patients with pN3 lymph node metastasis.

PMID- 17508257
TI  - Human health risk assessment of explosives and heavy metals at a military gunnery
      range.
AB  - In this research, a risk assessment was undertaken in order to develop the
      remediation and management strategy of a contaminated gunnery site, where a
      nearby flood controlling reservoir is under construction. Six chemicals,
      including explosives and heavy metals, posing potential risk to environmental and
      human health, were targeted in this study. A site-specific conceptual site model
      was constructed, based on effective, reasonable exposure pathways, to avoid any
      overestimation of the risk. Also, conservative default values were adapted to
      prevent underestimation of the risk when site-specific values were not available.
      The risks posed by the six contaminants were calculated using the API's Decision
      Support System for Exposure and Risk Assessment, with several assumptions. In the
      crater-formed-area (Ac), the non-carcinogenic risks (i.e., HI values) of tri
      nitro-toluene (TNT) and Cd were slightly larger than 1, but for RDX (Royal
      Demolition Explosives) was over 50. The total non-carcinogenic risk of the whole
      gunnery range was calculated to be 62.5, which was a significantly high value.
      The carcinogenicity of Cd was estimated to be about 10(-3), while that for Pb was
      about 5 x 10(-4), which greatly exceeded the generally acceptable carcinogenic
      risk level of 10(-4)-10(-6). It was concluded from the risk assessment that there
      is an immediate need for remediation of both carcinogens and non-carcinogens
      before construction of the reservoir. However, for a more accurate risk
      assessment, further specific estimations of the changes in environmental
      conditions due to the construction of the reservoir will be required; and more
      over, the effects of the pollutants to the ecosystem will also need to be
      evaluated.

PMID- 17508258
TI  - The effects of Acidithiobacillus ferrooxidans on the leaching of cobalt and
      strontium adsorbed onto soil particles.
AB  - Bioleaching from soil artificially contaminated with analogues of radionuclides,
      Co and Sr, was carried out using a Fe-oxidizing bacterium, Acidithiobacillus
      ferrooxidans. Due to bacterial metabolism, the pH and dissolved Fe(3+)
      concentration in a biotic slurry decreased and increased respectively, over time,
      but the concentrations of Co and Sr extracted from the soil showed no significant
      enhancement compared with those under abiotic control. In both cases, Co and Sr
      were leached from the soil during the initial period of the experiment, due to
      the initially low solution pH of 2.0, and the dissolved concentrations remained
      almost constant for the duration of the experiment (300 h). Since oxidation of
      Fe(2+) by A. ferrooxidans led to the production of Fe precipitates and colloidal
      suspensions, the Co and Sr extracted into solution were most likely re-adsorbed
      onto the Fe solids. Also, A. ferrooxidans, without an external supply of Fe(2+),
      extracted almost equal or greater amounts of Co and Sr from the soil than when
      Fe(2+) was supplied. Under the same leaching conditions, the extent of Sr removal
      was much lower than that of Co. On the contrary to the high efficiency of
      microbial metal leaching in biohydrometallurgy for low-graded sulfide ores, which
      has been widely documented, conventional bioleaching techniques with A.
      ferrooxidans supplied with enough Fe(2+) showed low efficiency for the removal of
      radionuclides loosely bound onto soil particle surfaces.

PMID- 17508259
TI  - Assessment of growth and stemwood quality of Scots pine on territory influenced
      by alkaline industrial dust.
AB  - Long-term influence of alkaline dust (pH 12.3-12.7) pollution emitted over 40
      years from a cement plant in Estonia was the reason of alkalisation (pH 6.7-7.9)
      and high concentrations of K, Ca and Mg in the soil of affected territories.
      Although dust emission has diminished during the last 10 years, the imbalances in
      nutrition substrate and their influence on the growth of trees are notable up to
      now. The study of morphological and physical properties of 70-80-year-old Scots
      pine (Pinus sylvestris L.) crown, stems and stemwood from three different air
      pollution zones showed serious deviations in comparison with a relatively healthy
      forest in an unpolluted area. The specimens from polluted trees, if compared to
      reference site, showed significantly smaller height growth, radial increment and
      width of annual rings of sapwood. In heartwood wider annual rings were found in
      polluted areas. In the period of heartwood formation the dust pollution level
      emitted from the plant was relatively modest and cement dust, which contains
      elements necessary for mineral nutrition of trees, may have acted as fertiliser.
      The moisture content in sapwood and heartwood, especially in the upper layers of
      stems, was lower in the polluted area than in reference site trees. Regression
      analysis revealed a strong dependence between latewood percentage and sapwood or
      heartwood in stems of Scots pine in all sample plots.

PMID- 17508260
TI  - Estimation of Polish cigarettes contamination with cadmium and lead, and exposure
      to these metals via smoking.
AB  - To estimate exposure to cadmium (Cd) and lead (Pb) through cigarette smoking, the
      concentrations of both metals in the blood or/and urine of smokers (20 cigarettes
      or more per day for 10 years or longer) and their non-smoking counterparts
      inhabiting an environmentally unpolluted area (Bialystok, Poland) were evaluated,
      as well as Cd and Pb contents in the cigarette brands (produced in Poland) smoked
      by the participants, including intact cigarettes, pre-smoking (tobacco, paper and
      filter) and post-smoking (butt, ash and smoke) cigarette components. Blood and
      urinary Cd concentrations in the smokers have been already reported by us to be 2
      4 times higher than in the non-smokers (Galazyn-Sidorczuk et al. Polish Journal
      of Environmental Studies, 13 (Suppl.1):91-95, 2004). All the other measurements
      are the subject of the present paper. Pb concentration in the blood of the
      cigarette smokers (52.12 +/- 15.51 microg l(-1)) was higher by 29% than in the
      non-smokers (40.42 +/- 11.19 microg l(-1)). The mean Cd and Pb contents in the
      cigarettes were 0.6801 +/- 0.1765 and 0.6853 +/- 0.0746 microg per cigarette,
      respectively. Under cigarette burning, performed using a machine for self-acting
      burning, on average 33% of Cd and 11% of Pb present in the whole cigarette was
      released into the smoke. For Cd, unlike Pb, there was a high positive correlation
      between the metal content in cigarettes and tobacco and its release into the
      smoke. Moreover, the subjects smoking cigarettes containing the highest Cd amount
      had higher blood Cd concentration than smokers of other cigarette brands. The
      results give clear evidence that in the case of inhabitants of areas unpolluted
      with Cd and Pb habitual cigarette smoking, due to tobacco contamination, creates
      a serious source of chronic exposure to these metals, especially to Cd.

PMID- 17508261
TI  - Distribution and contamination assessment of heavy metals in sediment of the
      Second Songhua River, China.
AB  - The Second Songhua River was subjected to a large amount of raw or primary
      effluent from chemical industries in Jilin city in 1960s to 1970s, resulting in
      serious mercury pollution. However, an understanding of other trace metal
      pollution has remained unclear. The objective of this study was to investigate
      trace metal contamination in the sediment of the river. Bottom sediment samples
      were taken in the river between Jilin city and Haerbin city in 2005. An
      uncontaminated sediment profile was taken in the Nen River at the same time.
      Total concentrations of Al, Fe, Mg, Ca, K, Na, Ti, Mn, V, Sc, Co, Cu, Cr, Ni, Pb
      and Zn in the sediment samples were measured by ICP-MS or ICP-OES, following
      digestion with various acids. Concentrations of Co, Cu, Cr, Ni, Pb and Zn in the
      surface sediments were 5.1-14.7, 18.5-78.9, 2.4-75.4, 7.2-29.0, 13.5-124.4, and
      21.8-403.1 mg/kg, respectively, generally decreasing along the course of the
      river from Jilin city to Haerbin city. Background concentrations of trace metals
      were reconstructed by geochemical normalization to a conservative element
      scandium. Results showed that concentrations of Co, Cr, and Ni in the sediment
      were generally only slightly higher than or equal to their background values,
      while concentrations of Cu, Pb, and Zn in the some sediment samples were
      significantly higher than their background values. In detail, the sediment at
      Jilin city was moderately contaminated by Cu, and the sediment of the Second
      Songhua River was moderately contaminated by Pb and Zn. The top layer (0-10 cm
      depth) and bottom layers (30-46 cm depth) of one sediment profile at Wukeshu town
      were generally moderately polluted by Pb and Zn. Synthetically, the surface
      sediment in the studied river section was classified as natural sediment without
      ecological risk by the sediment pollution index (SPI) of Cu, Cr, Ni, Pb and Zn.
      Only the 30-45 cm depth of the sediment profile at Wukeshu town was classified as
      low polluted sediment by the SPI of these metals, recording a historical
      contamination of the river in the 1960s to 1970s. This buried contamination of
      trace metals might pose a potential risk to water column under disturbance of
      sediment.

PMID- 17508262
TI  - Factor analysis and linear regression model (LRM) of metal speciation and physico
      chemical characters of groundwater samples.
AB  - An approach is described for viewing the interrelationship between different
      variables and also tracing the sources of pollution of groundwater of north
      Chennai (India). The data set of 43 variables which include major ions, minor
      ions and trace metal speciation (Cu, Pb, Cd and Zn) collected during the pre
      monsoon and post-monsoon seasons of the year 2000-2001, was subjected to R-mode
      factor analysis to comprehend the distribution pattern of the said variables. It
      was found that first factor measures salinity and hardness which explained 19.12%
      of the total variance (comprised of variables EC, TDS, Na+, K+, Ca2+, Mg2+, total
      hardness, Cl- and SO4(2-)) during pre-monsoon, while it was 25.08% during post
      monsoon. The second and third factors were attributed to speciation of zinc and
      copper ions during both pre-monsoon and post-monsoon. Although there were two
      more factors, loaded with speciation parameters of lead and cadmium, the variance
      of them were less than 10%. From this study it is seen that sea water intrusion,
      municipal solid waste disposal are the identified sources of component of
      pollution. The importance of metal ions is taking a secondary role and the
      anthropogenic origin-industrial activity, is the reason in the evaluation of
      pollution status as they come in the second, third, fourth and fifth factors. As
      the trace metal speciation was grouped in separate factors, linear regression
      model (LRM) with correlation analysis was applied to check its validity for
      prediction of speciation and to apply LRM for rapid monitoring of water
      pollution.

PMID- 17508263
TI  - Lead and cadmium concentrations in shorebirds from the Yeongjong Island, Korea.
AB  - This study presents concentration levels of pollutants (lead, and cadmium) in
      tissues (livers, kidneys, muscles, and bones) of shorebirds (Kentish Plovers (n =
      5), Mongolian Plovers (n = 2), Dunlins (n = 6), Great Knots (n = 10), Terek
      Sandpipers (n = 10)) from Yeongjong Island, Korea in the East Asian-Australian
      migration flyways during the autumn migration in 1994-1995. Lead concentrations
      in livers, in kidneys, in muscles, and in bones were significantly different
      among shorebird species. Lead concentrations in livers of Kentish Plovers (4.76
      +/- 2.72 microg/wet g), Mongolian Plovers (2.05 microg/wet g), Dunlins (3.77 +/-
      1.07 microg/wet g), and Great Knots (4.27 +/- 3.19 microg/wet g) were less than
      the toxic level, and lead concentrations in livers of Terek Sandpipers (1.20 +/-
      0.94 microg/wet g) were at the background level. Cadmium concentrations in
      livers, in kidneys, in muscles, and in bones did not vary among shorebirds, and
      concentrations of cadmium in livers and in kidneys were at background level
      (respectively, approximate 1 mug/wet g, approximate 2.67 microg/wet g) in all
      shorebird species. We suggest that interspecific differences of lead and cadmium
      concentrations were attributed to differences in exposure time and differences of
      diet, microhabitats in wintering ground. In livers and kidney of shorebirds from
      Yeongjong Island, lead and cadmium concentrations were higher than other
      locations previously reported.

PMID- 17508264
TI  - Prospective treatment in carnitine-acylcarnitine translocase deficiency.
AB  - Carnitine-acylcarnitine translocase (CACT) deficiency is a rare disorder that
      results in long-chain fatty acids being unavailable for mitochondrial beta
      oxidation and ketogenesis. It can present in the neonatal period or infancy with
      a severe clinical form, typically with convulsions, hypothermia, encephalopathy,
      cardiomyopathy and liver dysfunction, or with a milder phenotype with episodes of
      hypoglycaemia and hyperammonaemia during intercurrent illness. Investigations
      show hypoketonaemia, intermittent dicarboxyluria and hypocarnitinaemia with
      grossly elevated acylcarnitines. Enzyme assay or DNA analysis confirms the
      diagnosis. The severe phenotype results in severe disability or death. The less
      severe phenotype can also cause significant disability secondary to hypoglycaemia
      and/or hyperammonaemia at presentation. We report the outcome of two siblings
      with CACT deficiency. The index patient presented at the age of 2 months during a
      respiratory illness with hypoglycaemia, hyperammonaemia and cardiorespiratory
      collapse. Acylcarnitine profiles showed decreased free carnitine but striking
      elevations of long-chain acylcarnitines. Urine organic acids showed dicarboxylic
      aciduria. Fatty acid oxidation studies showed reduced oleate and myristate
      oxidation. His acylcarnitine profile normalized after he was started on a medium
      chain triglyceride (MCT) low-fat diet and carnitine supplementation. Low CACT
      activity on enzyme assay confirmed the diagnosis. He has resulting profound
      developmental delay and epilepsy. The sibling was prospectively treated with a
      low-fat MCT diet and carnitine supplementation. Acylcarnitine profile at birth
      also showed elevated long-chain acylcarnitines. Fatty acid oxidation studies
      confirmed the diagnosis. To date he has normal development and has not had any
      significant periods of hypoglycaemia or hyperammonaemia.

PMID- 17508265
TI  - Prenatal diagnosis by amniocentesis and chorionic villus biopsy of mtDNA mutation
      8993T > G.
AB  - The mtDNA mutation 8993T > G is associated with neurogenic muscle weakness,
      ataxia and retinitis pigmentosa (NARP) and Leigh syndrome. There are few reported
      cases of prenatal testing for mtDNA disorders. Specifically for 8993T > G, there
      are six cases in which prenatal diagnosis has been reported. We describe prenatal
      diagnosis in a 36-year-old G3P1 woman with 33% heteroplasmy in white blood cells.
      She had a previous child who died from Leigh disease (92% heteroplasmy). She
      underwent prenatal testing by both CVS and amniocentesis of the 8993T > G
      heteroplasmy levels. This is the first reported case in which both procedures
      were used. Heteroplasmy was similar in both tissues (58.6% CVS and 55%
      amniocentesis), in support of the theory that this testing is reliable and may be
      considered in prenatal cases where this mutation is known in the mother. To date,
      her child is 20 months old and developing normally. Heteroplasmy determination in
      the child was refused. Although the infant is developmentally normal, consistent
      with the observation that levels of heteroplasmy below 60% are compatible with a
      mild phenotype, this conclusion must be tempered by the limited period of
      observation and the fact that patients with the NARP phenotype often present
      later than 20 months of age.

PMID- 17508266
TI  - Mitochondrial disease: needs and problems of children, their parents and family.
      A systematic review and pilot study into the need for information of parents
      during the diagnostic phase.
AB  - OBJECTIVE: Firstly, this paper aims to systematically review the mitochondrial
      disease literature to identify studies assessing the needs and problems in the
      daily life of children with a mitochondrial disease and of their parents and
      family. The second aim is to provide more insight into the need for information
      by the parents of these children during the diagnostic process while in hospital.
      DESIGN: A systematic review and a pilot study, using a qualitative (focus group
      interviews; n = 7) and a quantitative (questionnaire; n = 37) design. RESULTS:
      Mothers reported great socioeconomic and psychoaffective strain and showed
      psychopathological symptoms in the two studies published with respect to this
      topic. The pilot study showed that parents considered an honest and interested
      attitude of the person who is giving the information as most important.
      Furthermore they wanted oral and written information and a central point where
      they could go with their questions at any time they felt the need. The need for
      information increased during the four phases of the diagnostic process and was
      highest in the fourth phase. CONCLUSIONS: The few studies found in the review,
      combined with expectations that having a mitochondrial disease must have a great
      impact on these children and their parents and family, call for more research in
      their needs and problems. Furthermore, there are gaps in the current information
      provision to parents of these children. A better understanding of the needs and
      problems of these children and their family is essential for effective care
      planning and might result in an improved quality of life.

PMID- 17508267
TI  - Reproducible transfection in the presence of carrier DNA using FuGENE6 and
      Lipofectamine2000.
AB  - We have examined transfection conditions of chinese hamster ovary cells using
      FuGENE6 and immortalized gonadotrope cell line LbetaT2 cells using Lipofectamin
      2000 and to obtain reproducible and reliable transfection. The experiments were
      performed with fluorescent protein expression vectors, pEYFP-C1 and pECFP-C1, or
      secreted-type alkaline phosphatase vector, pSEAP2, as reporter genes. The number
      of cells that received reporter plasmid increased in proportion to the amount of
      DNA and reached a plateau at a large amount. Co-transfection using two
      fluorescence vectors with a small amount of DNA demonstrated that every
      transfected cell received both vectors without discrimination. The results
      further indicate that there is a hierarchy of DNA receptiveness among competent
      cells. Simultaneously, we observed that a reliable transfection took place at the
      high dose of DNA. That is, the addition of carrier DNA makes possible a reliable
      delivery of a small amount of DNA of interest to the competent cells. Similar
      results were also obtained by pSEAP2 vector. Co-transfection of pEYFP-C1 and
      pECFP-C1 with various ratios at adequate amounts demonstrated that the
      fluorescence intensities by each vector are proportional to each amount of vector
      used with comparable efficiency. In addition, we observed that the variation of
      the assay using fluorescent vectors or secreted alkaline phosphatase vectors were
      small enough within the +/- 25% (SD, n = 4), showing that the internal marker
      often used to normalize the data is not essential, since the vectors used allow
      us to exclude cell-harvest and cell-lysis. Thus, the present study demonstrates
      that the addition of carrier DNA during transfection provides reproducible and
      reliable results.

PMID- 17508268
TI  - Mind the gap! Three approaches to scarcity in health care.
AB  - This paper addresses two ways in which scarcity in health care turns up and three
      ways in which this dual condition of scarcity can be approached. The first
      approach is the economic approach, which focuses on the causes of cost-increase
      in health care and on developing various mechanisms of rationing and priority
      setting in health care. The second approach is the justice approach, which
      interprets scarcity as one of the Humean [Symbol: see text]Circumstances of
      Justice.' Whereas these approaches interpret scarcity as a given fact, the third
      approach casts doubt on this interpretation. Rather, it interprets scarcity as a
      social, anthropological, and technologically induced construction of Modernity.
      This paper supports the theories of Hans Achterhuis, Ivan Illich, and Nicholas
      Xenos but also further elaborates their views with regard to health care by
      offering an approach to scarcity that interprets it as an economic translation of
      finitude. I argue that this approach, which entails a contemporary revaluation of
      the ancient Socratic attitude on human life and finitude, will be better able to
      deal with the pressing contemporary issues of setting limits on health care
      because it mitigates contemporary health care's tendency toward infinity in
      meeting - and creating - health care needs.

PMID- 17508269
TI  - Delivery of cancer genetics services: The Royal Marsden telephone clinic model.
AB  - We have conducted a telelink telephone-led cancer genetic counselling model at
      The Royal Marsden NHS Foundation Trust. The study commenced in March 2004 and
      evaluation of the clinic was conducted over 17 months from March 2005 to the end
      of July 2006. A total of 612 patients had telephone consultations during this
      time, 228 of whom were referred from primary care with a median of 30 patients
      counselled per month (range of 19-63, depending on staff availability with
      average of two staff per clinic). Waiting times were measured for General
      Practitioner referrals and all 228 were counselled within the national target
      stipulated 13 weeks (median 6 weeks, range 1-12). An additional 132 patients who
      were sent appointment letters after receipt of their family history
      questionnaires did not attend their appointments (18% of all potential referrals)
      and required recontacting by letter. After telephone counselling, 42% of patients
      were able to be discharged from the telephone clinic without a subsequent face-to
      face appointment, thereby saving resources. The telephone clinic also had a short
      set-up time with flexibility on timing and day of administration, which would be
      an advantage in centres where outreach clinic facilities are scarce. The telelink
      telephone counselling model is highly efficient in triaging high risk individuals
      for face-to-face counselling as per the Kenilworth model, in effecting
      concentration of resources and in providing a flexible individual-centred
      approach to cancer genetic counselling delivery.

PMID- 17508270
TI  - Nurse-led cancer genetics clinics in primary and secondary care in varied ethnic
      population areas: interaction with primary care to improve ascertainment of
      individuals from ethnic minorities.
AB  - Genetic services are receiving increasing numbers of referrals of people with a
      family history of cancer for assessment of genetic risk, and therefore need to
      find cost-effective ways of meeting this rising demand. General Practitioners
      (GPs) are known to be reluctant to take on genetic consultations. Current
      evidence suggests that black and ethnic minorities are poorly represented in
      cancer genetics clinics. Nurse-led clinics in primary care have been found to be
      successful. This paper reports a pilot study to test the feasibility,
      accessibility, and effectiveness of providing cancer genetics nurse-counsellor
      clinics in primary and secondary care in the SW Thames Region. We initially set
      up three nurse-led clinics in general practices and two in district hospitals
      with very different ethnic catchment areas. The service was advertised by
      displaying posters and leaflets, translated into different languages. Self
      referrals were encouraged. We set up a user involvement sub-group and held two
      focus group meetings to assess barriers to, and satisfaction with, the service. A
      patient satisfaction questionnaire was designed and administered after the
      appointments. We also designed a GP satisfaction survey regarding the service.
      Data on referrals, including their source and outcome, were recorded on a purpose
      designed study database. We received increasing numbers of referrals to all
      clinics over the course of the pilot. Of 137 referrals, 23 (17%) were from ethnic
      minorities, of whom 17/23 (74%) were self-referred, compared with 102 British
      White referrals, of whom 91/102 (89%) were self-referred. Sixty-two patients
      (45%) were assessed to be at population risk and reassured, 60 (44%) were at
      moderate risk, and 15 (11%) were at high risk and were referred on for
      appropriate management. These proportions were similar for black and ethnic
      minority patients. Most patients reported high satisfaction with the service.

PMID- 17508271
TI  - The Teesside cancer family history service: change management and innovation at
      cancer network level.
AB  - The Teesside project took the underlying principle of the Kenilworth model--that
      people with a family history of cancer should be 'triaged' and signposted to
      appropriate clinical services--and applied it to a whole clinical cancer network
      in which inequity was the major driver for change. Unlike the Kenilworth model,
      the Department of Health/Macmillan Cancer Support-funded pilot project in
      Teesside embedded genetic risk assessment at secondary care level. The project
      took a 'bottom up' approach that engaged a wide variety of stakeholder groups and
      identified key challenges that formed the basis of a clear strategic plan. A
      number of specialist cancer nurses across the network had independently developed
      risk assessment roles over preceding years: these roles needed to be redefined
      prior to the creation of a small team of genetic risk assessment practitioners
      ('GRAPs'). This innovation challenged existing nursing roles on a local and
      national level. In turn, however, we were able to introduce a simple, single
      network-wide referral pathway, reducing workload on both primary care and tumour
      specific services; to adopt a standardised genetic risk assessment pathway; and
      to incorporate risk assessment as a key step in the decision to enroll an
      individual in a clinical screening programme. Collaborative audit proved to be a
      useful way of engaging stakeholders and holding their attention throughout the
      three-year project, proving the value of the project in their terms, and
      embedding the changes we had made. The keys to success in this project were
      inclusiveness, transparency and clear strategic management.

PMID- 17508272
TI  - Basic and clinical characteristics of PDE 3 inhibitors as cardiotonic agents.

PMID- 17508273
TI  - Erythropoietin prevents PC12 cells from 1-methyl-4-phenylpyridinium ion-induced
      apoptosis via the Akt/GSK-3beta/caspase-3 mediated signaling pathway.
AB  - Apoptosis is a contributing cause of dopaminergic neuron loss in Parkinson
      disease. Recent work has shown that erythropoietin (EPO) offers protection
      against apoptosis in a wide variety of tissues. We demonstrate that exposure of
      PC12 cells to 1-methyl-4-phenylpyridinium ion (MPP(+)) with recombinant human
      EPO, significantly decreased apoptosis as measured by TUNEL and caspase-3
      activity when compared to MPP(+) treatment alone. EPO induced sustained
      phosphorylation of Akt and its substrate, GSK-3beta, reduced caspase-3 activities
      in PC12 cells. The anti-apoptotic effect of EPO was abrogated by co-treatment
      with LY294002, the specific blocker of phosphatidylinositol 3-kinase (PI3K). The
      effects of EPO on GSK-3beta and caspase-3 activities were also blocked by
      LY294002. LiCl, the inhibitor of GSK-3beta, downregulated the caspase-3 activity
      and blocked the apoptosis induced by MPP(+). Finally, we determined that EPO
      transiently activated the ERK signaling pathway, but PD98059, a specific
      inhibitor of ERK, does not alter the survival effect of EPO in this model system.
      Thus, these findings indicate that EPO protects against apoptosis in PC12 cells
      exposed to MPP(+), through the Akt/GSK-3beta/caspase-3 signaling pathway, but the
      ERK pathway is not involved in the EPO-dependent survival enhancing effect in
      this model system.

PMID- 17508274
TI  - Risk assessment and genetic counseling for hereditary breast and ovarian cancer:
      recommendations of the National Society of Genetic Counselors.
AB  - These cancer genetic counseling recommendations describe the medical,
      psychosocial and ethical implications of identifying at-risk individuals for
      hereditary breast and ovarian cancer (HBOC) through cancer risk assessment, with
      or without genetic susceptibility testing. They were developed by members of the
      Practice Issues Subcommittee of the National Society of Genetic Counselors'
      Familial Cancer Risk Counseling Special Interest Group. The information contained
      in this document is derived from extensive review of the current literature on
      cancer genetic risk assessment as well as the professional expertise of genetic
      counselors with significant experience in education and counseling regarding
      hereditary breast and ovarian cancer. Critical components of the process include
      the ascertainment of medical and family histories, determination and
      communication of cancer risk, assessment of risk perception, education regarding
      the genetics of HBOC, discussion of molecular testing for HBOC if appropriate
      (including benefits, risks and limitations) and any necessary follow-up. These
      recommendations do not dictate an exclusive course of management or guarantee a
      specific outcome. Moreover, they do not replace the professional judgment of a
      health care provider based on the clinical situation of a client.

PMID- 17508275
TI  - Accuracy of self-reported personal history of cancer in an outpatient breast
      center.
AB  - The self-reporting of cancer history is becoming increasingly important, as it
      frequently guides medical decision-making. We studied the accuracy of personal
      cancer history using a self-administered questionnaire, comparing the results
      with the Tumor Registry at our institution. Among 39,662 records, we identified
      3614 women with a single cancer in the Tumor Registry who reported none or one
      cancer on their questionnaire. The sensitivity in self-reporting cancers was
      85.7%, ranging from 92.1% for breast cancer to 42.9% for leukemia. The accuracy
      for breast cancer and Hodgkin's Lymphoma was significantly better than other
      cancers (p=0.00027, CI: 1.4-3.88). Analysis of patient's characteristics showed
      that Caucasians reported breast cancer more accurately than Asian/Pacific
      Islanders (p=0.008), and those with Jewish ancestry more accurately than non
      Jewish (p=0.0435). These results will help us to improve data collection and thus
      improve medical decision-making.

PMID- 17508276
TI  - Ready or not--intrapartum prevention of perinatal HIV transmission in Illinois.
AB  - OBJECTIVES: The overall readiness of Illinois birthing hospitals to comply with
      the 2003 Illinois HIV Perinatal Prevention Act and prevent perinatal HIV
      transmission, and the hospital characteristics that predict readiness were
      examined. METHODS: Nurse Managers of all 137 Illinois birthing hospitals were
      surveyed regarding current labor and delivery (L&D) practices for HIV status
      identification, documentation, testing and zidovudine (AZT) availability in March
      2004. Bivariate and multivariable regression analysis was performed. RESULTS: All
      137 hospitals returned the surveys. Almost forty seven percent of Illinois
      birthing hospitals had adequate maternal HIV status documentation on arrival in
      L&D, 72.3% documented prenatal HIV results in the L&D chart, 65.7% documented
      prenatal HIV in the newborn chart, 38.7% ordered HIV tests on L&D if no prenatal
      HIV status was available, and 61.3% had AZT available. Only 17 hospitals (12.4%)
      met requirements for overall readiness to prevent perinatal HIV transmission.
      Sixteen hospitals (11.6%) met a minimal level of readiness (prenatal HIV status
      documentation and AZT availability). CONCLUSIONS: Despite passage of legislation
      to increase perinatal HIV testing and reduce transmission, Illinois birthing
      hospitals had an overall low level of readiness to implement the intrapartum
      interventions that are an essential part of eradicating pediatric HIV infection.
      Perinatal reduction protocols and implementation guidelines would improve the
      overall readiness of Illinois birthing hospitals to prevent perinatal HIV
      transmission.

PMID- 17508277
TI  - Computational analysis and identification of amino acid sites in dengue E
      proteins relevant to development of diagnostics and vaccines.
AB  - We have identified 72 completely conserved amino acid residues in the E protein
      of major groups of the Flavivirus genus by computational analyses. In the dengue
      species we have identified 12 highly conserved sequence regions, 186 negatively
      selected sites, and many dengue serotype-specific negatively selected sites. The
      flavivirus-conserved sites included residues involved in forming six disulfide
      bonds crucial for the structural integrity of the protein, the fusion motif
      involved in viral infectivity, and the interface residues of the oligomers. The
      structural analysis of the E protein showed 19 surface-exposed non-conserved
      residues, 128 dimer or trimer interface residues, and regions, which undergo
      major conformational change during trimerization. Eleven consensus T(h)-cell
      epitopes common to all four dengue serotypes were predicted. Most of these
      corresponded to dengue-conserved regions or negatively selected sites. Of special
      interest are six singular sites (N(37), Q(211), D(215), P(217), H(244), K(246))
      in dengue E protein that are conserved, are part of the predicted consensus T(h)
      cell epitopes and are exposed in the dimer or trimer. We propose these sites and
      corresponding epitopic regions as potential candidates for prioritization by
      experimental biologists for development of diagnostics and vaccines that may be
      difficult to circumvent by natural or man-made alteration of dengue virus.

PMID- 17508278
TI  - Racial/ethnic differences in internalizing and externalizing symptoms in
      adolescents.
AB  - The prevalence of most adult psychiatric disorders varies across racial/ethnic
      groups and has important implications for prevention and intervention efforts.
      Research on racial/ethnic differences in the prevalence of internalizing and
      externalizing symptoms and disorders in adolescents has been less consistent or
      generally lacking. The current study examined the prevalence of these symptom
      groups in a large sample of sixth, seventh, and eighth graders in which the three
      major racial/ethnic groups in the U.S. (White, Black, and Hispanic/Latino) were
      well-represented. Hispanic females reported experiencing higher levels of
      depression, anxiety, and reputational aggression than other groups. Black males
      reported the highest levels of overtly aggressive behavior and also reported
      higher levels of physiologic anxiety and disordered eating than males from other
      racial/ethnic groups. Hispanic females also exhibited higher levels of
      comorbidity than other racial/ethnic groups.

PMID- 17508279
TI  - Cancer-specific targeting of a conditionally replicative adenovirus using mRNA
      translational control.
AB  - BACKGROUND: In view of the limited success of available treatment modalities for
      a wide array of cancer, alternative and complementary therapeutic strategies need
      to be developed. Virotherapy employing conditionally replicative adenoviruses
      (CRAds) represents a promising targeted intervention relevant to a wide array of
      neoplastic diseases. Critical to the realization of an acceptable therapeutic
      index using virotherapy in clinical trials is the achievement of oncolytic
      replication in tumor cells, while avoiding non-specific replication in normal
      tissues. In this report, we exploited cancer-specific control of mRNA translation
      initiation in order to achieve enhanced replicative specificity of CRAd
      virotherapy agents. Heretofore, the achievement of replicative specificity of
      CRAd agents has been accomplished either by viral genome deletions or
      incorporation of tumor selective promoters. In contrast, control of mRNA
      translation has not been exploited for the design of tumor specific replicating
      viruses to date. We show herein, the utility of a novel approach that combines
      both transcriptional and translational regulation strategies for the key goal of
      replicative specificity. METHODS: We describe the construction of a CRAd with
      cancer specific gene transcriptional control using the CXCR4 gene promoter (TSP)
      and cancer specific mRNA translational control using a 5'-untranslated region (5'
      UTR) element from the FGF-2 (Fibroblast Growth Factor-2) mRNA. RESULTS: Both in
      vitro and in vivo studies demonstrated that our CRAd agent retains anti-tumor
      potency. Importantly, assessment of replicative specificity using stringent tumor
      and non-tumor tissue slice systems demonstrated significant improvement in tumor
      selectivity. CONCLUSIONS: Our study addresses a conceptually new paradigm: dual
      targeting of transgene expression to cancer cells using both transcriptional and
      mRNA translational control. Our novel approach addresses the key issue of
      replicative specificity and can potentially be generalized to a wide array of
      tumor types, whereby tumor selective patterns of gene expression and mRNA
      translational control can be exploited.

PMID- 17508280
TI  - Preconditioning in humans.
AB  - Brief ischemia to the myocardium initiates a cascade of biochemical events in
      cardiac myocytes that protects the heart muscle during subsequent ischemic
      insults. This phenomenon is called ischemic preconditioning. If an acute
      myocardial infarction is preceded by preinfarction angina, it results in smaller
      infarction size, fewer cardiac arrhythmias, and better-left ventricular function.
      During coronary intervention, brief balloon inflation protects the heart during
      subsequent inflations. Patients vary in the degree of preconditioning and those
      patients who have the ability to demonstrate a significant preconditioning effect
      will have lesser incidence of subsequent cardiac events. Preconditioning protects
      the myocardium during coronary artery bypass surgery, particularly in the off
      pump procedure, yet the thoracic surgery community has not universally adopted
      this technique.

PMID- 17508281
TI  - Cardioprotection in females: a role for nitric oxide and altered gene expression.
AB  - A number of epidemiological and animal studies have suggested a cardioprotective
      role for estrogen. This review will focus on the cardioprotective role of
      estrogen in ischemia-reperfusion injury. Estrogen binding to receptors can lead
      to altered gene expression and estrogen has been shown to induce expression of a
      number of genes that have been suggested to be important in cardioprotection.
      Estrogen is reported to increase expression of the plasma membrane glucose
      transporter GLUT4 and to increase carbohydrate metabolism. Estrogen has also been
      reported to increase mitochondrial biogenesis and to alter mitochondrial
      generation of reactive oxygen species. Estrogen results in upregulation of
      cardiac eNOS and nNOS, which have been shown previously to be important mediators
      of cardioprotection. Nitric oxide has been shown to result in S-nitrosylation and
      inhibition of the L-type calcium channel, thereby reducing calcium loading during
      ischemia. Nitric oxide has also been reported to inhibit complex I and inhibition
      of complex I has been reported to reduce activation of the mitochondrial
      permeability transition pore. Nitric oxide has been shown to result in activation
      of the mitochondrial K(ATP) channel, which has been shown to be involved in
      cardioprotection. Estrogen can also activate rapid non-genomic pathways that
      activate cardioprotective-signaling pathways such as the phosphatidylinositol-3
      kinase (PI-3 kinase) pathway which has also been shown to initiate protection.
      Taken together, estrogen by genomic and non-genomic pathways can result in the
      initiation of a number of signaling pathways that enhance cardioprotection.

PMID- 17508282
TI  - An introduction to acute heart failure syndromes: definition and classification.

PMID- 17508284
TI  - A noninvasive parametric evaluation of stress effects on global cardiovascular
      function.
AB  - Stress has been recognized as an important contributing factor to many forms of
      cardiovascular diseases. Its quantification has been sought for decades, but to
      no avail. We have developed a wholly noninvasive approach to quantitatively
      assess mental and physical stress effects on parameters that are associated with
      global cardiovascular function. Blood pressure, electrocardiogram, respiration
      and pulse volume are recorded simultaneously in experimental subjects during
      imposed arithmetic mental stress and Valsalva maneuver. Results show that
      parameters related to heart rate variability, respiratory rate, T-wave amplitude
      and pulse transit time are significantly modified during stress. Changes in these
      parameters involved differing mechanisms, although complex, can be delineated
      with logical analysis of electrophysiological, hemodynamic and neurogenic
      origins. This noninvasive technique is useful for both psychological evaluation
      and for clinical stress management.

PMID- 17508283
TI  - Iron: the Redox-active center of oxidative stress in Alzheimer disease.
AB  - Although iron is essential in maintaining the function of the central nervous
      system, it is a potent source of reactive oxygen species. Excessive iron
      accumulation occurs in many neurodegenerative diseases including Alzheimer
      disease (AD), Parkinson's disease, and Creutzfeldt-Jakob disease, raising the
      possibility that oxidative stress is intimately involved in the neurodegenerative
      process. AD in particular is associated with accumulation of numerous markers of
      oxidative stress; moreover, oxidative stress has been shown to precede hallmark
      neuropathological lesions early in the disease process, and such lesions, once
      present, further accumulate iron, among other markers of oxidative stress. In
      this review, we discuss the role of iron in the progression of AD.

PMID- 17508285
TI  - Microfluidic device for cell capture and impedance measurement.
AB  - This work presents a microfluidic device to capture physically single cells
      within microstructures inside a channel and to measure the impedance of a single
      HeLa cell (human cervical epithelioid carcinoma) using impedance spectroscopy.
      The device includes a glass substrate with electrodes and a PDMS channel with
      micro pillars. The commercial software CFD-ACE+ is used to study the flow of the
      microstructures in the channel. According to simulation results, the probability
      of cell capture by three micro pillars is about 10%. An equivalent circuit model
      of the device is established and fits closely to the experimental results. The
      circuit can be modeled electrically as cell impedance in parallel with dielectric
      capacitance and in series with a pair of electrode resistors. The system is
      operated at low frequency between 1 and 100 kHz. In this study, experiments show
      that the HeLa cell is successfully captured by the micro pillars and its
      impedance is measured by impedance spectroscopy. The magnitude of the HeLa cell
      impedance declines at all operation voltages with frequency because the HeLa cell
      is capacitive. Additionally, increasing the operation voltage reduces the
      magnitude of the HeLa cell because a strong electric field may promote the
      exchange of ions between the cytoplasm and the isotonic solution. Below an
      operating voltage of 0.9 V, the system impedance response is characteristic of a
      parallel circuit at under 30 kHz and of a series circuit at between 30 and 100
      kHz. The phase of the HeLa cell impedance is characteristic of a series circuit
      when the operation voltage exceeds 0.8 V because the cell impedance becomes
      significant.

PMID- 17508286
TI  - Microfluidic self-assembly of live Drosophila embryos for versatile high
      throughput analysis of embryonic morphogenesis.
AB  - A method for assembling Drosophila embryos in a microfluidic device was developed
      for studies of thermal perturbation of early embryonic development. Environmental
      perturbation is a complimentary method to injection of membrane-impermeable
      macromolecules for assaying genetic function and investigating robustness in
      complex biochemical networks. The development of a high throughput method for
      perturbing embryos would facilitate the isolation and mapping of signaling
      pathways. We immobilize Drosophila embryos inside a microfluidic device on
      minimal potential-energy wells created through surface modification, and
      thermally perturb these embryos using binary laminar flows of warm and cold
      solutions. We self-assemble embryos onto oil adhesive pads with an alcohol
      surfactant carrier fluid (detachment: 0.1 mL/min), and when the surfactant is
      removed, the embryo-oil adhesion increases to approximately 25 mL/min flow rates,
      which allows for high velocities required for sharp gradients of thermal binary
      flows. The microfluidic thermal profile was numerically characterized by
      simulation and experimentally characterized by fluorescence thermometry. The
      effects of thermal perturbation were observed to induce abnormal morphogenetic
      movements in live embryos by using time-lapse differential interference contrast
      (DIC) microscopy.

PMID- 17508287
TI  - Fabrication of UV epoxy resin masters for the replication of PDMS-based
      microchips.
AB  - This paper presents two methods for the fabrication of UV epoxy resin masters for
      the replication of PDMS-based microfluidic chips. In the first method, the epoxy
      resin master is fabricated from a negative glass template manufactured using
      conventional lithography and wet etching techniques. However, in the second
      method, the master is produced simply by exposing a layer of UV epoxy resin
      coated on a glass substrate. Although the first method enables the replication of
      multiple PDMS structures from a single master, the latter method avoids the
      requirement for a wet chemical etching process and enables the epoxy master to be
      produced in 40 min or less. The experimental results show that the epoxy resin
      masters enable the mass production of PDMS replicas with highly precise
      geometrical tolerances. A series of electrokinetic focusing experiments are
      performed using PDMS microchips replicated from the current epoxy resin masters.
      The experimental results obtained for the width of the electrokinetically-focused
      sample stream under different focusing ratios are found to be in good agreement
      with the theoretical predictions. The sample handling characteristics of the
      microfluidic chips are also investigated. It is shown that the sample flow can be
      electrokinetically pre-focused into a narrow stream and then guided to the
      desired outlet port by applying a simple voltage control model. Finally, it is
      demonstrated that through an appropriate alignment of the sample flow and the
      conductivity gradient, the electrokinetic instability phenomenon can be induced
      at a relatively low electrical field strength of 0.35 kV/cm.

PMID- 17508288
TI  - Automatic microfluidic platform for cell separation and nucleus collection.
AB  - This study reports a new biochip capable of cell separation and nucleus
      collection utilizing dielectrophoresis (DEP) forces in a microfluidic system
      comprising of micropumps and microvalves, operating in an automatic format. DEP
      forces operated at a low voltage (15 Vp-p) and at a specific frequency (16 MHz)
      can be used to separate cells in a continuous flow, which can be subsequently
      collected. In order to transport the cell samples continuously, a serpentine
      shape (S-shape) pneumatic micropump device was constructed onto the chip device
      to drive the samples flow through the microchannel, which was activated by the
      pressurized air injection. The mixed cell samples were first injected into an
      inlet reservoir and driven through the DEP electrodes to separate specific
      samples. Finally, separated cell samples were collected individually in two
      outlet reservoirs controlled by microvalves. With the same operation principle,
      the nucleus of the specific cells can be collected after the cell lysis
      procedure. The pumping rate of the micropump was measured to be 39.8 microl/min
      at a pressure of 25 psi and a driving frequency of 28 Hz. For the cell separation
      process, the initial flow rate was 3 microl/min provided by the micropump. A
      throughput of 240 cells/min can be obtained by using the developed device. The
      DEP electrode array, microchannels, micropumps and microvalves are integrated on
      a microfluidic chip using micro-electro-mechanical-systems (MEMS) technology to
      perform several crucial procedures including cell transportation, separation and
      collection. The dimensions of the integrated chip device were measured to be 6x7
      cm. By integrating an S-shape pump and pneumatic microvalves, different cells are
      automatically transported in the microchannel, separated by the DEP forces, and
      finally sorted to specific chambers. Experimental data show that viable and non
      viable cells (human lung cancer cell, A549-luc-C8) can be successfully separated
      and collected using the developed microfluidic platform. The separation accuracy,
      depending on the DEP operating mode used, of the viable and non-viable cells are
      measured to be 84 and 81%, respectively. In addition, after cell lysis, the
      nucleus can be also collected using a similar scheme. The developed automatic
      microfluidic platform is useful for extracting nuclear proteins from living
      cells. The extracted nuclear proteins are ready for nuclear binding assays or the
      study of nuclear proteins.

PMID- 17508289
TI  - Micropatterned surfaces of PDMS as growth templates for HEK 293 cells.
AB  - In this paper the easy and reliable preparation of precise micropatterns on PDMS
      surfaces is described and the growth of HEK 293 cells on those patterns during
      culture over several days is examined. The first patterning approach described is
      based on soft-lithography and polyelectrolyte multilayer deposition. Two
      different soft-lithographic techniques are employed for creating surface patterns
      of PAH, PSS, untreated and oxidized PDMS. The growth behavior of HEK 293 cells is
      investigated on all the dual combinations of the four surfaces, and decreasing
      preference of the cells for the surfaces in the order PAH (-NH2)>ox-PDMS (
      OH)>>PSS (-SO3-)>PDMS (-CH3) is revealed. As the second patterning approach a
      method is introduced, which allows the deposition of gel droplets in a microarray
      format utilizing differences in the surface wettability. This concept is new and
      expected to be very useful for various applications. Finally, a speculative
      explanation for the different cell spreading behavior is provided considering the
      interplay between individual cell-surface interactions and a permanent cell
      tractional force.

PMID- 17508290
TI  - Genetic susceptibility to breast cancer.
AB  - Deleterious mutations in two breast and ovarian cancer susceptibility genes,
      BRCA1 and BRCA2 have been identified in breast and ovarian cancer families. Women
      with a BRCA1 or BRCA2 mutation are candidates for additional risk reduction
      measures such as intensive screening, prophylactic surgery or chemoprevention.
      Additional susceptibility genes have been identified, including PTEN, ATM, TP53,
      CHEK2, CASP8, PBRL and BRIP1. Yet, many women with a personal or family history
      suggestive of a hereditary susceptibility to breast cancer undergo genetic
      testing and no significant genetic alteration is found. Thus, there are other
      susceptibility genes that have not been identified, and it is likely that the
      remaining familial contribution to breast cancer will be explained by the
      presence of multiple low penetrance alleles that coexist to confer high
      penetrance risks (a polygenic model). The American Cancer Society has identified
      cancer prevention as a key component of cancer management and there is interest
      in developing individualized cancer prevention focused on identifying high risk
      individuals who are most likely to benefit from more aggressive risk reduction
      measures. Breast cancer risk assessment and genetic counseling are currently
      provided by genetic counselors, oncology nurse specialist, geneticists, medical
      and surgical oncologists, gynecologists and other health care professionals,
      often working within a multidisciplinary clinical setting. Current methods for
      risk assessment and predictive genetic testing have limitations and improvements
      in molecular testing and risk assessment tools is necessary to maximize
      individual breast cancer risk assessment and to fulfill the promise of cancer
      prevention.

PMID- 17508291
TI  - [The virtue of that precious balsam...: approach to Don Quixote from the
      psychopharmacological perspective].
AB  - The most outstanding novel of the Spanish literature, Don Quixote, represents the
      source to which the different specialists who intend to deepen their knowledge of
      the late Renaissance society usually address. This masterpiece of Miguel de
      Cervantes has been frequently approached from the psychopathological perspective
      to obtain a psychiatric diagnosis of its main character, Alonso Quijano. Also,
      other clinical approaches from the traumatological and general therapeutical view
      (oils, ointments, balms and other pharmacy preparations) have been frequent. We
      have tackled Don Quixote from the psychopharmacological perspective, a barely
      explored field. In this work, we intend to study the therapeutical cures used
      during the Cervantine time for the treatment of insane and mentally disturbed
      people (sedatives like opium, laxatives like hellebore, tonics, irritants and
      surgical techniques like bloodlettings and <<fuentes>>) and we analyze the
      limited and unspecific therapies, mainly of herbal origin (balms, purgatives and
      emetics), which Cervantes reveals to us in his novel. Among them, rhubarb root
      (Rumex alpinus), seeds of spurge (Euphorbia lathyris), St. John's Wort (Hypericum
      perforatum), main ingredient of Aparicio's oil, and rosemary (Rosmarinus
      officinalis), primary component of the famous balsam of Fierabras, should be
      highlighted. We have also examined the possible scientific influences which might
      have inspired Cervantes in this field, mainly the works of Juan Huarte de San
      Juan The examination of men's wits and the one of Andres Laguna Dioscorides'
      materia medica.

PMID- 17508292
TI  - [Duration of untreated psychosis as predictive and prognostic factor in the
      course of first episode psychosis].
AB  - INTRODUCTION: Recently, many studies have focused on the duration of untreated
      psychosis (DUP) in order to clarify if DUP could be one of the factors that would
      influence prognosis of psychotic disease. MATERIAL AND METHODS: We present a one
      year follow - up study with 90 medication native, first episode psychotic
      patients. The likely prognosis factors that could influence in the outcome of the
      disease were measured. Therefore, we used a protocol including the following
      scales: PANSS, Psychosocial Stress Global Assessment scale (DSM IIIR), Global
      Assessment of Functioning scale (GAF-EEAG), Clinical Global Impression (CGI),
      Montgomery-Asberg scale for the depression, Young mania rating scale, abnormal
      involuntary movements scale, UKU scale for extrapyramidal symptoms and Premorbid
      Adjustment scale (Cannon-Spoor). Assessments were made every three months for 1
      year. A statistical analysis of data was performed. RESULTS: As a result, it was
      concluded that there was no relationship between a long duration untreated
      psychosis and a worse outcome of the illness in our sample. The only related
      factors with the prognosis were premorbid adjustment and the type of disease
      onset. Hence, the patients with a better premorbid adjustment and an acute onset
      of psychosis had a better outcome. CONCLUSION: Our study represents more evidence
      in favor of the independence of DUP and disease outcome.

PMID- 17508293
TI  - [Delirium rating scale-revised-98 (DRS-R-98): Colombian adaptation of the Spanish
      version].
AB  - INTRODUCTION: Delirium is associated with high morbidity and mortality. There are
      no available instruments validated for evaluation and follow-up of this syndrome
      in Columbia. METHODS: An expert's panel adapted the Spanish DRSR- 98. In 110,
      randomly selected, medical-surgical hospitalized patients, 17 (15.5 %) of them
      with delirium diagnosed with DSM-IV-TR criteria, the inter-rater reliability,
      validity and sensitivity to clinical change of the new adaptation of the scale
      were measured. RESULTS: Internal consistency (Cronbach's alpha: 0.956), inter-
      rater reliability (ICC: 0.95) and validity (94.8 % under the ROC curve area) were
      very good. For the Cut-off score of 14 for the total scale score, sensitivity was
      82.4% and specificity 97.8 %. The scale was sensitive to clinical change, with a
      mean difference of 12.9 (t: 4.071; p=0.007). CONCLUSIONS: The Colombian
      adaptation of the Spanish DRS-R-98 is sensitive, specific and reliable for
      assessment of delirium in hospitalized adults in medical surgical settings.

PMID- 17508294
TI  - [Prefrontal dysfunction in schizophrenia: implication is associative
      recognition].
AB  - OBJECTIVE: We used an event related functional magnetic resonance imaging (fMRI)
      method to examine the neural basis of associative recognition memory deficit in
      schizophrenia. METHODS: Fifteen people with schizophrenia and 18 healthy control
      subjects were scanned with fMRI while performing a memory task (coding and
      recognition) of visual objects. During coding, the subjects studied items and
      pairs of items. During recovery, the subjects had to recognize items (old/new
      decisions) and recognize associations (intact/rearranged decisions). The study
      design was based on a random effect model and the fMRI analysis was restricted to
      correct items only. RESULTS: At the behavioral level, both groups performed
      equally well on item recognition, whereas people with schizophrenia demonstrated
      poorer performance on associative recognition. At the brain level, comparison
      between associative and item recognition tasks revealed greater left dorsolateral
      prefrontal and right inferior prefrontal activations in the control group
      relative to the schizophrenia group. CONCLUSIONS: The findings of this fMRI study
      suggest the prefrontal cortex as the basis for the selective memory deficit for
      associative recognition observed in schizophrenia.

PMID- 17508295
TI  - [Cannabis consumption and development of psychosis: state of the art].
AB  - Cannabis is the most widely used illegal drug in Spain. Currently, its use is on
      the rise as risk perception is decreasing, primarily among young people. It is
      well known that cannabis negatively influences course and prognosis in
      schizophrenic patients. However, the relationship between cannabis use and
      development of a psychotic or schizophrenic disorder remains controversial. The
      study of this topic has been approached using longitudinal cohort studies, which
      study cannabis use and psychotic or schizophrenic disorders. In addition to the
      classic Swedish conscript study published by Andreasson et al. 1987, during the
      past years, six more longitudinal cohort studies have been published. The data
      demonstrate that there are both temporal and dose-response relationships, and
      that early initiation of cannabis use is highly correlated with the development
      of psychotic symptoms. Cannabis consumption can increase the risk of developing
      schizophrenia in a vulnerable population twofold, to the extent that some studies
      suggest a causal relationship. The current knowledge base makes it necessary to
      warn the population about the relationship between cannabis use and the
      development of psychosis.

PMID- 17508296
TI  - [Cognitive-behavioral therapy for the treatment of cocaine dependence].
AB  - The past two decades have been characterized by marked progress in the
      development of effective cognitive- behavioral therapies for cocaine dependence,
      for which no generally effective pharmacotherapies have been identified. The
      increasing literature on the efficacy of several types of cognitive-behavioral
      therapies (community reinforcement approach plus vouchers, cue exposure
      treatment, relapse prevention therapy and motivational interviewing) for cocaine
      use disorders is reviewed, followed by discussion of a number of issues that
      arise when integrating these cognitive-behavioral interventions into clinical
      practice. Overall, this review describes a vigorous area of research that has
      much to contribute to the treatment of cocaine use disorders.

PMID- 17508297
TI  - [Electroconvulsive therapy in the treatment of bipolar depression].
AB  - Since its introduction, electroconvulsive therapy is a treatment used in mood
      disorders, especially in the depressive phases of bipolar disorder. The advance
      of this technique has made it a useful and current option both in the treatment
      of acute phases as in the prevention of recurrences. The objective of this
      revision is to collect available data about the use of electroconvulsive therapy
      in bipolar depression. Its indications, effectiveness, prediction and patterns of
      response are included in this work, together with its complications, adverse
      events and drug interactions. Differences in response between bipolar and
      unipolar depression are also discussed.

PMID- 17508298
TI  - [Auditory gating deficits in schizophrenia: unimodal or heteromodal
      dysfunction?].
AB  - Failure filtering out redundant auditory information is the most replicated
      neurophysiological abnormality observed in patients with schizophrenia. However,
      the brain structures involved in this deficit remains obscure. Two main
      hypotheses have been proposed to explain this phenomenon. The first maintains
      that the auditory gating deficit in schizophrenia is related to abnormal function
      of microcircuits within the hippocampal formation. The second hypothesis proposes
      that the deficit may be linked to impaired prefrontal cortex function. In both
      scenarios, auditory gating is conceptualized as a process dependent on the
      functional indemnity of cortical areas that integrate information from different
      sensory modalities. When filtering out redundant information, heteromodal
      cortices (hippocampal formation or prefrontal cortex), ensure that redundant
      stimuli do not reach higher-order levels of information processing in the brain
      and do not interfere with working memory performance. Findings from our lab,
      using magnetoencephalography (MEG), and data from other labs using
      electroencephalography (EEG), suggest an alternative hypothesis. We hypothesize
      that auditory gating deficit in schizophrenia is due to the abnormal function of
      unimodal microcircuits within left auditory cortex, independent from
      abnormalities in heteromodal cortices. Explaining whether auditory gating deficit
      in schizophrenia is determined by a primary dysfunction of unimodal or multimodal
      cortices may help elucidate the mechanisms involved in the sensory information
      overload and the characteristic cognitive deficits found in this disorder.

PMID- 17508299
TI  - [Psychogenic psychosis].
AB  - In 1916, Wimmer described psychogenic psychosis as psychosis secondary to mental
      trauma. Psychogenic psychoses are currently included in acute and transient
      psychotic disorders (F23) in the ICD-10 and in the brief psychotic disorders
      (298,8) in the DSM-IV-TR. We present a case report of psychogenic psychosis in a
      39 year-old female and analyze it with the predisposition-trauma mental model.

PMID- 17508300
TI  - [Dementias: diagnostic contribution of imaging and proton magnetic resonance
      spectroscopy].
AB  - INTRODUCTION: The objective is analyze the complementarity between 1H magnetic
      resonance spectroscopy (MRS) and magnetic resonance (MR) imaging in the global
      diagnosis of Alzheimer's disease (AD) or vascular dementia (VD). METHODS: We
      studied 168 patients with cognitive impairment from AD, VD, mild cognitive
      impairment (MCI) and major depression. All patients were evaluated by brain MR
      imaging and MRS using two sample volumes localized at right medial temporal gyrus
      and posterior parietal gyrus. Metabolites analyzed were N-acetylaspartate (NAA),
      myo-Inositol (mI), Choline (Cho) and creatine (Cr), as standard references for
      obtaining the Co/Cr, mI/Cr and NAA/Cr ratios. Imaging and spectroscopy
      alterations were graded from 0 to 4 and the average of both was used to draw ROC
      and SROC curves. Area under ROC curve (Az) was used as a measure of
      discriminative ability. RESULTS: Combination of MR imaging and MRS significantly
      improved AD diagnosis (Global Az: 0.722 vs. MR imaging Az: 0.624; p: 0.003).
      However, the combination of MR imaging and MRS did not improve VD diagnosis. SROC
      curve obtained for the diagnosis of global dementia was Az: 0.6658 with 0.67
      sensitivity and 0.65 specificity. CONCLUSIONS: Combination of both MR techniques
      significantly improved AD diagnosis versus MR imaging alone. More studies are
      needed to enhance VD classification. Metabolic data found by MRS can be useful to
      differentiate cognitive impairment

PMID- 17508301
TI  - [Use of specific drugs for Alzheimer's disease].
AB  - OBJECTIVE: To evaluate the consumption evolution and financial impact of specific
      treatments for Alzheimer's disease (AD) in Aragon (Spain), analyzing consumption
      patterns and trends, and to estimate the proportion of AD patients treated with
      these drugs. METHODS: Descriptive study of outpatient utilization of
      cholinesterase inhibitors and memantine (1996-2004), obtained from the drug
      packages dispensed by community pharmacists through prescriptions charged to the
      National Health Service. According to the defined daily doses (DDD) and
      expenditure data available, data were expressed in DDD per 1,000 inhabitants per
      day (DHD), DDD per 1,000 inhabitants older than 64 (DHD65), first-last year
      increase (%), drug consumption pattern, annual cost per inhabitant and daily
      treatment cost (DTC). To estimate the proportion of treated patients we compared
      the DHD65 data with the estimated AD prevalence. RESULTS: Overall consumption of
      these drugs has increased from 0.026 DHD (1996) to 3.235 DHD (2004). Donepezil
      remains as the most prescribed, though it is proportionally decreasing as a
      result of the quick introduction of newer alternatives. Overall cost of the DHD
      dispensed in 2004 reached nearly 6 million euros. DTC decreased about 30% over
      the study period, but the total cost increased ninety-fold (sixty-fold when non
      variable euros from 2004 were considered). According to our estimates, 34% of
      people with AD were receiving specific treatment. CONCLUSIONS: There is a
      significant increase in the consumption and economical burden of these drugs,
      whose cost-effectiveness has been questioned in some studies. More studies
      including specific patient data are needed in order to identify individual
      characteristics and evaluate treatment appropriateness.

PMID- 17508302
TI  - [Adaptation and validation of a naming test in Spanish speakers. Do demographic
      variables show the evolutive pattern towards Alzheimer's disease?].
AB  - INTRODUCTION: Naming is one of the most mentioned functions regarding aging and
      dementia. Nevertheless, inconsistent findings have been reported in relation to
      demographic variables in healthy people. OBJECTIVE: The effect of demographic
      variables on naming performance was studied in a sample of Spanish speaking
      volunteers. METHODS: The test was based initially on the nouns used by Oldfield
      and Wingfield in English. Data were obtained from 438 healthy subjects whose age
      range was from 9 to 90 years old. There were 274 females and 164 males, 31% of
      whom had first level of educational background, 34% had second level and 34%,
      third or university level. Trifactorial ANOVA was carried out on either correct
      responses or the average time required per word, with gender, age and education
      as independent variables. RESULTS: Performance was related to age, gender and
      education. A significant triple interaction was observed for both correct
      responses and time. A figure throughout time showed that performance was mainly
      affected in women of greater age and, within this group, in women with lower
      educational level. DISCUSSION: The evolution observed in this function emulates
      the progressive cognitive pattern, which is to be expected in people most prone
      to develop Alzheimer's disease. Considering the reported relationship among
      semantic memory, cognitive impairment and dementia, the results obtained with the
      present sample are also promising for the conceptual validity of the instrument.
      The test, with original drawings, is freely offered for research.

PMID- 17508303
TI  - [Neurological disorders in the narrative works of Benito Perez Galdos].
AB  - INTRODUCTION: Benito Perez Galdos was a realistic writer. As such, he was devoted
      to displaying reality in its full complexity. He shared the traits of
      experimental medicine of Claude Bernard (Introduction a l'etude de la medecine
      experimentale). The writer was a close friend of famous contemporary doctors
      (Gregorio Maranon, Manuel Tolosa Latour), had textbooks with neurological
      content, and was familiar with Charcot. METHODS: With this background, we have
      foreseen neurological descriptions in his works. To search for them, we have
      reviewed three paramount novels: Fortunata y Jacinta, La de Bringas and Tormento.
      RESULTS: We found: a) headache, usually migraine with and without aura; common
      precipitants and inheritance are present. The novelist himself suffered from
      severe migraine; b) movement disorders: Parkinson syndrome and hemifacial spasm;
      c) convulsive and non-convulsive epilepsy in a girl as well as syncope and
      psychogenic loss of consciousness; d) congenital syphilis, based on a typical
      physical appearance in a character with madness (paranoid schizophrenia); the
      reason was probably that syphilis was regarded as the most common cause of
      "dementia praecox"; e) alcoholism: acute intoxication, deprivation, behavior
      disorders, hepatic encephalopathy and a likely pellagra; f) sleep disorders:
      parasomnias (somnambulism, somniloquy) and sleep paralysis, and g) stroke and
      also inverted metamorphopsia of psychogenic origin. CONCLUSION: Ailments and
      disease pervaded life in the 19th century. Neurological disorders were highly
      prevalent and are fully integrated into Galdos realistic works. Many of them
      fulfill criteria of disorders contemplated according to degeneration theories.
      Nevertheless, humanitarian features raise the characters above their tragic
      destiny. Biographical factors, particularly his many love affairs and his
      political implication as a liberal, could have contributed to the plethora of
      precise descriptions.

PMID- 17508304
TI  - [Psychometry of dementias at debate].
AB  - The accurate diagnosis of dementias and the screening of cognitive impairment
      constitute a key to attend to the sociodemographical needs. This paper states the
      aims of screening and diagnosis, the tools used and their main psychometric
      features, especially, reliability and validity. The need to critically review the
      publications on this subject is highlighted and the Standards for Reporting of
      Diagnostic Accuracy (STARD) are mentioned. In addition, some proposals and
      recommendations from literature are cited and reviewed. Finally, the tests
      studied and used most by Spanish neurologists are commented on. The MMSE (Mini
      Mental Status Examination), the MIS (Memory Impairment Screen) and the Eurotest
      stand out.

PMID- 17508305
TI  - [Neurological complications of the human immunodeficiency virus (HIV) infection].
AB  - Human immunodeficiency virus infection (HIV) is entering into its third decade
      affecting more than 40 million persons on the plane, with an extraordinary
      incidence in the underdeveloped world, especially in the African continent where
      more than 25 million are affected, with more than 3 million new yearly infections
      and where the life expectancy is at 47 years. Although the vaccination is still
      far away, the introduction of combined antiretroviral therapy in the middle of
      the 90's was an important advance that contributed to converting an infection
      that previously had a very high rate of short-term mortality into a chronic
      disease. The neurological complications of this infection vary enormously. They
      affect any location of the neuroaxis and can appear at any stage of infection. It
      is not rare that more than one neurological complication exists. Such
      complications may be a consequence of the infection itself (primary) or related
      with immune depression accompanying it (secondary). Among the former, dementia
      associated to HIV and peripheral polyneuropathy stand out. Among the latter,
      opportunistic viral and fungal infections and lymphoma of the nervous systems
      stand out. In recent years different tests that help to establish the diagnoses
      of these entities have been developed, a necessary step to initiate adequate
      therapies. The immune state of the patient, reflected by the peripheral count of
      CD4 lymphocytes and serum viral load, helps us to establish the most likely
      causes of the neurological problems that appear in the context of this infection.
      We briefly review the most outstanding characteristics of each one of them in
      this work.

PMID- 17508306
TI  - [Segmental spinal dysgenesis].

PMID- 17508307
TI  - [Multiple meningiomas].

PMID- 17508308
TI  - [Relapsing meningoencephalitis as onset of Behcet's disease].
AB  - INTRODUCTION: Behcet's disease is a systemic, chronic, relapsing inflammatory
      disease of unknown etiology characterized by recurrent oral aphthae, genital
      ulcerations and uveitis. The main pathological mechanism is leukocytoclastic
      vasculitis. CLINICAL CASE: We present the case of a patient with Behcet's disease
      that presented as a relapsing meningoencephalitis with lymphocytic pleocytosis
      and high protein levels in cerebrospinal fluid. The MRI revealed a lesion in the
      brain stem and part of diencephalon. CONCLUSIONS: The central nervous system is
      involved in up to 5%-20% of patients with Behcet's disease, this being the first
      manifestation in 3% of the cases. Clinical course includes: patients with an
      isolated episode with complete or incomplete recovery, relapsing and remitting
      forms, progressive forms or asymptomatic neurological involvement. The most
      frequent presentation is relapsing meningoencephalitis, with progressive course
      localized in the brain stem. Prognosis varies according to the type of neurologic
      process. The worse outcome is in the parenchymal forms with brain stem and spinal
      cord involvement. It also depends on the pathological findings in the
      cerebrospinal fluid, and the number of total events or recurrences after tapering
      the glucocorticoids. Mortality rate is high, up to 20% of cases after 7 years in
      patients with neurological involvement.

PMID- 17508309
TI  - [Type 1 glutaric aciduria: clinical and therapeutic implications].
AB  - INTRODUCTION: Type 1 glutaric aciduria is a genetic disease that produces a
      deficiency in the glutaryl CoA dehydrogenase enzyme. This deficiency entails an
      elevation of glutaric acid and 3-OH glutaric acid. Dystonia is the predominant
      symptom. The symptoms appear after an asymptomatic period during the first months
      of life. It may present chronically and insidiously or acutely as metabolic
      encephalopathy during a banal infectious condition or vaccination. Treatment with
      Carnitine, protein restriction and early approach of the hypermetabolism
      conditions has been shown to be effective in decreasing the encephalopathy
      episodes in the first years of life. CASE REPORT: A 16 year old woman with
      macrocrania and picture of insidious onset of left hemidystonia from 6 months of
      age. Early treatment was begun as she had a sister suffering from type 1 glutaric
      aciduria. She has a clinical picture with less seriousness than her sister even
      though both have the same genotype. CONCLUSIONS: This disease must be considered
      when there is dystonic cerebral palsy and paternal consanguinity. Early onset of
      treatment could entail a decrease in the symptoms even in cases of insidious
      initiation. This would suggest therapeutic maintenance even after having passed
      the age in which acute encephalopathies occur.

PMID- 17508310
TI  - [Heterogeneous topography of Foix-Chavany-Marie syndrome].
AB  - INTRODUCTION: Bilateral facio-pharyngo-laryngo-glosso-masticatory palsy with
      automatic-voluntary dissociation is known as Foix-Chavany-Marie (FCM) syndrome.
      It is usually due to bilateral cortical lesions involving both anterior opercula
      (biopercular syndrome). We describe three patients with FCM syndrome associated
      with ischemic lesions in two atypical localizations: a) bilateral subcortical
      infarcts, and b) unilateral opercular infarct. CASES REPORT: Patient 1, a 66 year
      old male, was admitted for a sudden onset of anarthria and facial, lingual and
      masticatory paralysis. Neurological examination revealed automatic-voluntary
      dissociation of facial motility. MRI showed an acute left subcortical infarct and
      multiple bilateral subcortical ischemic lesions. Patient 2, a 61 year old male,
      also suffered a sudden onset of anarthria, with bilateral facial and lingual
      paralysis and automatic-voluntary dissociation together with sudden onset
      swallowing alteration. MRI showed a single ischemic lesion involving the left
      operculum. Patient 3, a 36 year old male, presented sudden onset of dysarthria,
      dysphagia and bilateral facial palsy with automatic-voluntary dissociation and
      loss of force in left upper limb. MRI showed an acute right opercular infarct and
      no contralateral lesions. CONCLUSIONS: FCM syndrome is not only due to bilateral
      opercular lesions but can also be seen in bilateral subcortical and even
      unilateral opercular lesions.

PMID- 17508311
TI  - How affect regulation moderates the association between anxious attachment and
      neuroticism.
AB  - Correlations between anxious attachment and neuroticism (usually about .40 to
      .50) prompt questions about whether self-reported anxious attachment captures a
      key construct in attachment theory or if it reflects a more general personality
      trait instead. A college sample of late adolescents and young adults (N = 287)
      was used to show that questionnaire measures of neuroticism and anxious
      attachment do not have a simple linear association; instead, neuroticism and
      anxious attachment have a more complex dynamic relationship that is moderated by
      avoidant attachment, an attachment style that reflects an interpersonally derived
      strategy for affect regulation. The association between neuroticism and anxious
      attachment is further moderated by conscientiousness, a personality trait that
      may reflect a more biologically mediated system of affect regulation. These
      separate moderating effects and the different affect regulation systems they
      reflect are discussed in the context of longstanding debates about how
      personality traits and attachment styles influence each other.

PMID- 17508312
TI  - Insecure family bases and adolescent drug abuse: a new approach to family
      patterns of attachment.
AB  - A new approach to assessing family attachment patterns is presented, using a
      composite measure of individual attachment representations based on the
      Bartholomew Attachment Interview. A cluster analysis yielded three different
      patterns in a sample of N = 37 families with a drug dependent adolescent (age 14 
      25) and both biological parents. A "triangulated" pattern (mothers: preoccupied;
      fathers: dismissing; adolescents: fearful) was found in 65% of the sample. A
      total of 19% showed an "insecure" pattern (mothers, fathers, and adolescents:
      fearful) and 16% a "near-secure" pattern (mothers and adolescents: secure;
      fathers preoccupied). Preliminary comparisons between these groups indicate
      differences in comorbid psychiatric disorders, in individual and family
      functioning, but not in addiction severity. There is a trend towards differences
      in outcome of family therapy. Implications for treatment and further research are
      discussed.

PMID- 17508313
TI  - A pilot study of attachment patterns in adult twins.
AB  - The hypothesis that attachment in adults is influenced by genetic factors was
      investigated. The within-pair differences in attachment representation in same
      sex monozygotic and dizygotic twins were compared using the Adult Attachment
      Interview (AAI). The results showed a clear tendency toward monozygotic twins (n
      = 28) being more concordant than dizygotic twins (n = 13), but the within-pair
      similarity was also high in both zygosity groups. The results suggest, in
      behavior genetic terms, that heredity and shared environment may contribute to
      attachment status in adulthood. This differs from studies of attachment in
      infancy and early childhood, which report attachment to be explained mainly by
      shared environment, with minimal influence from genetic factors. Furthermore, the
      results showed that the distribution of the attachment pattern in twins had the
      same percentage distribution as reported for singletons. Consequently, there was
      no tendency toward more insecure attachment in twins than in singletons.

PMID- 17508314
TI  - Childhood maltreatment, complex trauma symptoms, and unresolved attachment in an
      at-risk sample of adolescent mothers.
AB  - Associations between unresolved attachment, abuse history, and a wide range of
      trauma-related symptomatology were examined in an at-risk sample (N = 62). Fifty
      percent reported severe childhood physical and/or sexual abuse. An independent
      trauma interview elicited more reports of childhood sexual abuse than the Adult
      Attachment Interview (AAI); conversely, the AAI elicited more reports of physical
      abuse. Childhood physical abuse, sexual abuse, and general maltreatment were
      associated with unresolved status. Furthermore, sexual abuse history and general
      maltreatment predicted unresolved loss, suggesting that they adversely affected
      the integration of other emotional and/or traumatic experiences. Women classified
      as Unresolved reported higher levels of dissociation, confusion regarding self
      identity, and relationship problems. Findings complement and extend empirical
      support for the theorized association between dissociative processes and
      unresolved attachment.

PMID- 17508315
TI  - The impact of attachment on dementia-related problem behavior and spousal
      caregivers' well-being.
AB  - This study investigated the impact of attachment style on the course of dementia
      related problem behavior and caregivers' well-being over 2 years. A total of 116
      married couples with one spouse suffering from dementia participated. Care
      recipients' and caregivers' attachment styles were assessed at the beginning of
      the study. Caregivers' well-being and care recipients' dementia-related problem
      behavior were assessed three times (n = 68). Husbands' and wives' attachment
      styles were significantly associated. Caregivers' avoidance and care recipients'
      insecure attachment style were associated with increased levels of dementia
      related problem behavior. Caregivers' avoidance and anxiety were also associated
      with lower levels of caregivers' well-being. The latent growth curve analysis
      indicated that problem behavior and attachment style are associated, and that
      both have direct effects on caregivers' well-being.

PMID- 17508316
TI  - Indigenous Australians' understandings regarding mental health and disorders.
AB  - The purpose of the present paper was to determine what is currently documented
      about Indigenous Australians' understandings of mental health and mental
      disorders through a meta-synthesis of peer-reviewed qualitative empirical
      research. The following databases were electronically searched (1995-April 2006):
      AOA-FT and AIATSIS, Blackwell Synergy, CINAHL and Pre CINHAL, Health source:
      nursing/academic edition, Medline, Proquest health and medical complete,
      PsycInfo, Science Direct, Synergy and HealthInfoNet. Eligible studies were those
      written in English and published in peer-reviewed journals, empirical studies
      that considered Indigenous people's understandings of mental health and provided
      details on methodology. Five articles from four qualitative studies met these
      criteria. Meta-ethnography was used to identify common themes emerging from the
      original studies. Reciprocal translation was used to synthesize the findings to
      provide new interpretations extending beyond those presented in the original
      studies. An overarching theme emerged from the synthesis: the dynamic
      interconnectedness between the multi-factorial components of life circumstances.
      Reciprocal translations and synthesis regarding Indigenous understandings of
      mental health and illness resulted in five themes: (i) culture and spirituality;
      (ii) family and community kinships; (iii) historical, social and economic
      factors; (iv) fear and education; and (v) loss. The application of a meta
      synthesis to these qualitative studies provided a deeper insight into Indigenous
      people's understandings of mental health and illness. The importance of
      understanding Indigenous descriptions and perceptions of mental health issues is
      crucial to enable two-way understandings between Indigenous people's constructs
      of wellness and Western biomedical diagnostic labels and treatment pathways for
      mental disorders and mental health problems.

PMID- 17508317
TI  - Comparison of diagnostic guidelines for juvenile bipolar disorder.
AB  - The purpose of the present paper was to compare currently available diagnostic
      guidelines for juvenile bipolar disorder with respect to utility in research and
      clinical practice. A systematic search of psychiatric, medical and psychological
      databases was conducted using the terms 'juvenile bipolar disorder', 'paediatric
      bipolar disorder' and 'guidelines'. Three main sets of guidelines issued by the
      National Institute of Health and Clinical Excellence (UK), The National Institute
      of Mental Health (USA) and Child Psychiatric Workshop (USA) were found. There
      were key differences in the recommendations made by each regarding the diagnosis
      and symptomatic presentation of juvenile bipolar disorder. Although the diagnosis
      of juvenile bipolar disorder is gaining increased recognition, its definition
      remains controversial. It is recommended that clinicians and researchers need to
      develop diagnostic guidelines that have clinical salience and can be used for
      future research by incorporating key features of those that are currently
      available.

PMID- 17508318
TI  - Early psychosis in rural areas.
AB  - Early psychosis (EP), in which the terms first-episode psychosis or first-break
      psychosis are also considered, is an area of developing research intensity.
      Although it is apparent that considerable progress has been made in establishing
      best practice criteria and protocols for EP in general, the particular issues
      pertaining to rural areas have not received the same attention. The purpose of
      the present study was to conduct a systematic review of the literature of early
      psychosis programmes, initiatives and research in rural areas in order to help
      establish the best available evidence. The authors conducted a systematic search
      of major electronic databases, based on the NHMRC hierarchy of evidence, an
      established scale, for identified early psychosis cross-referenced with multiple
      rural terms, between the years 1995 and 2005. A total of 637 articles met the
      initial search criteria; 206 were identified as having primary significance;
      three dealt specifically with rural areas. There is a paucity of research
      findings or published literature concerning the specific needs or characteristics
      of early psychosis practice or service delivery in rural areas. A number of
      inferences and suggestions for further research, investigations and policy
      directions are put forward for consideration.

PMID- 17508319
TI  - Diagnostic stability 2 years after treatment initiation in the early psychosis
      intervention programme in Singapore.
AB  - OBJECTIVE: To evaluate the diagnostic stability of psychotic disorders over a 2
      year period in patients presenting with first-episode psychosis. METHODS: One
      hundred and fifty-four patients were recruited from an early psychosis
      intervention programme (EPIP). They were diagnosed by the attending psychiatrist
      using the Structured Clinical Interview for DSM-IV Axis I at first contact
      (baseline) and after 24 months. The diagnoses were classified into the following
      categories: schizophrenia spectrum disorders (schizophrenia, schizophreniform
      disorder and schizoaffective disorder), affective psychosis (bipolar and major
      depressive disorders with psychotic symptoms), and other non-affective psychosis
      (delusional disorder, psychosis not otherwise specified and brief psychotic
      disorder). Two measures of stability, the prospective and the retrospective
      consistency were determined for each diagnosis. RESULTS: The diagnoses with the
      best prospective consistency were schizophrenia (87.0%) and affective psychosis
      (54.5%). The shift into schizophrenia spectrum disorder was the most frequent
      diagnostic change. Duration of untreated psychosis was found to be the only
      significant predictor of shift. CONCLUSION: It is difficult to make a definitive
      diagnosis at first contact. The clinical need to review the diagnosis throughout
      the period of follow up is emphasized.

PMID- 17508320
TI  - Group intervention for coexisting psychosis and substance use disorders in rural
      Australia: outcomes over 3 years.
AB  - OBJECTIVE: Outpatient group interventions have been shown to be efficacious in
      reducing substance use among people with psychosis. This is the first Australian
      study to report on the effectiveness of such interventions provided in a rural
      area by mental health and drug and alcohol clinicians, with follow up over 3
      years. The primary aim was to investigate whether an open-ended weekly outpatient
      group intervention, consisting of motivational interviewing (MI) and cognitive
      behaviour therapy (CBT), was effective in reducing substance use and improving
      symptomatology and general functioning among people with psychosis. METHOD: This
      was a service evaluation project, with clinician-administered ratings made for
      four retrospective 3 monthly baseline observations and up to 12 3 monthly post
      recruitment observations. RESULTS: Thirty-nine participants entered the group
      intervention, with an average attendance of 28.51 sessions (SD=24.61). Compared
      to a baseline period of 1 year, the group intervention was associated with
      significant improvements in substance use, symptomatology, treatment non
      compliance, overall functioning and unscheduled service use. A median split
      according to treatment group attendance indicated that there was no difference in
      improvement profiles on a factor reflecting overall severity among those who
      attended fewer (mean=10.63) versus more sessions (mean=45.50), but there was a
      sharper reduction in the use of acute mental health services among those who
      attended more sessions. CONCLUSIONS: Significant change in functioning (including
      substance use and symptomatology) can occur within the context of a regular but
      relatively short outpatient group intervention, delivered in addition to usual
      treatment. However, extended group attendance over a 1 year period may be further
      associated with prevention of relapse and less unscheduled service use.

PMID- 17508321
TI  - Process of care in general hospital psychiatric units: national survey in Italy.
AB  - OBJECTIVE: To investigate the process of care in Italian public acute inpatient
      facilities. METHOD: Each facility's head psychiatrist (in all Italian regions
      except Sicily) completed a structured interview concerning provision of treatment
      and facility rules. RESULTS: Twenty-three university psychiatric clinics with 399
      beds (mean=17.3 beds), 16 24 h community mental health centers with 98 beds
      (mean=6.1 beds), and 262 general hospital psychiatric units with 3431 beds
      (mean=13.1 beds) were surveyed. Mean length of stay was 18.5+/-7.1 days, 37.0+/
      55.3 days and 12.0+/-3.4 days, respectively. Pharmacotherapy was ubiquitous.
      Approximately 80% of facilities held regular clinical evaluations, supportive
      talks, and counselling. Dynamic focused psychotherapy was available in 29% of the
      facilities; 24% provided cognitive behavioural therapy; 32% family therapy; and
      39% structured rehabilitative intervention. Vocational training and activities
      targeted at helping patient integration into their local communities were
      uncommon. Most facilities did not allow the possession of cutting utensils (96%),
      personally possessed medication (96%), or lighters (72%), and most had locked
      doors (75%). Fewer facilities (37%) prohibited the use of mobile phones (32%) and
      metal knives during meal times (37%). Frequency of physical restraint was
      associated with number of internal rules. Delivery of psychotherapy was
      associated with nurse provision. CONCLUSIONS: The process of psychiatric
      inpatient care in Italy shows considerable variability. Future clinical practice
      guidelines should address the currently limited provision of evidence-based
      psychosocial intervention in these facilities. Efforts should also be devoted to
      improving the effectiveness of the hospital-community mental health service
      interface.

PMID- 17508322
TI  - Suicide in New South Wales Prisons, 1995-2005: towards a better understanding.
AB  - OBJECTIVES: This paper reports on a review of suicides in New South Wales (NSW)
      prisons from 1 January 1995 to 31 December 2005 in an attempt to gain a better
      understanding of the nature and quality of the problem of suicide among
      prisoners. METHOD: All deaths in NSW prisons for the period were reviewed. Those
      identified as self-inflicted, with a coronial finding of death by suicide or
      those awaiting a coronial hearing but reported as possible death by suicide were
      included. A data set was collected on each case and entered into a database.
      RESULTS: A total of 92 cases were identified as deaths by suicide in NSW prisons
      from 1 January 1995 to 31 December 2005, representing 41% of all deaths in
      custody for the period. CONCLUSION: The rate of suicide in NSW prisons has been
      declining over the past 10 years, but remains approximately 10-fold that of the
      NSW community. Suicide was the leading cause of death among NSW inmates from 1995
      to 2005. Suicide is a rare event, making its prediction a difficult task, with
      the prison environment a further compounding factor. This review highlights a
      number of factors, which appear to be common in many cases. Increased monitoring
      during the first week of incarceration may be an effective intervention. It is
      recommended that consideration be given to the length of time spent on remand and
      the value of custodial sentences of <or=6 months.

PMID- 17508323
TI  - Rural/urban differences in the distribution of eating disorder symptoms among
      adolescents from community samples.
AB  - OBJECTIVE: Rural/urban differences in the prevalence of mental disorders have
      often been reported in the last 30 years, among others in the distribution of
      eating disorder symptoms and suicide rates. The role of sex, age and
      socioeconomic status in the differences by place of residence has often been
      neglected in past studies. METHOD: Two independent community samples of students
      (mean age=17.4 years, SD=1.4), taken from among those attending high school in an
      urban district (Cagliari; n=817) and in a rural one (Carbonia; n=507) of south
      Sardinia, Italy, were invited to fill in the Eating Attitudes Test (EAT), the
      Bulimic Investigatory Test of Edinburgh (BITE), the Body Attitudes Test (BAT) and
      the revised Hopkins Symptom checklist (SCL-90-R). RESULTS: Female students scored
      higher than male students on all inventories. In male participants, the scores on
      the EAT were higher in the urban than in the rural sample. Conversely, in both
      male and female students the rural sample reported higher scores on the BITE
      symptoms subscale. When the comparison was confined to the fraction of those who
      scored higher than the suggested cut-off on the EAT and the BITE, students in the
      urban sample outnumbered those in the rural sample. No other differences were
      found. Socioeconomic status and age did not influence the differences in the
      reporting of eating disorder symptoms by place of residence. CONCLUSIONS:
      Although caution is required when reading the findings drawn from self-report
      instruments, it is evident that the factors influencing the distribution of
      eating disorder symptoms and their psychological correlates by place of residence
      are far more complex than currently thought.

PMID- 17508324
TI  - Restraint and eating concern in North European and East Asian women with and
      without eating disorders in Australia and Singapore.
AB  - OBJECTIVE: To investigate eating disorder psychopathology, restraint and eating
      concern in young women with and without an eating disorder from two different
      ethnic groups in Australia and Singapore. METHOD: The relationship of Eating
      Disorder Examination Questionnaire Global, Restraint and Eating Concern scores to
      cultural orientation and sociocultural factors was analysed in 154 women with and
      without an eating disorder. Participants were from the following backgrounds:
      North European Australian, East Asian Australian, Singaporean Chinese and North
      European expatriates in Singapore. RESULTS: Women with eating disorders had
      similar psychopathology across the cultural groups. Among controls, Singaporean
      Chinese reported significantly greater overall eating disorder psychopathology
      than other cultural groups and greater restraint than North European
      Australians/expatriates. Eating concern was not associated with cultural group
      overall or acculturation to Western culture. Dissatisfaction with family
      functioning, socioeconomic status and education level were not significantly
      associated with any of the eating disorder measures. CONCLUSION: In eating
      disorder psychopathology, the specific symptom of eating concern may transcend
      cultural influences.

PMID- 17508325
TI  - Maternal partner criminality and cannabis use in young adulthood: prospective
      study.
AB  - OBJECTIVES: The present study examined whether the experience of the arrest or
      incarceration of a mother's partner before a child reached 14 years of age was
      associated with use of cannabis in early adulthood and, if so, whether this
      association was confounded or mediated by other factors. METHOD: Data were from
      the Mater Hospital University of Queensland Study of Pregnancy, a prospective
      birth cohort study in Brisbane, Australia. The history of partner arrest and
      incarceration was reported by mothers at the 14 year follow up. Mothers were
      divided into four groups: mothers whose partner had no history of arrest or
      incarceration, mothers reporting partner arrest, mothers reporting partner
      incarceration, and unpartnered mothers. Young adults' cannabis use was assessed
      at 21 years. Other covariates were prospectively measured between birth and 14
      years. RESULTS: After controlling for potential confounding and mediating
      factors, frequent use of cannabis at age 21 was more likely among young adults
      with a history of maternal partner arrest (odds ratio=2.3; 95% confidence
      interval: 1.4-3.8). There was no significant association between maternal partner
      incarceration or single motherhood, and cannabis use at age 21. CONCLUSIONS:
      Arrest of the mother's partner before the child is 14 is associated with that
      child's increased cannabis use at age 21 but this does not appear to be the case
      for children whose fathers have been imprisoned. It appears that for children
      whose fathers have been arrested, the father's ongoing presence in the family may
      result in worse outcomes for the child, including an increased risk of cannabis
      use in young adulthood.

PMID- 17508326
TI  - Effects of methylphenidate on cognition and behaviour: ruptured communicant
      aneurysm of the anterior artery.

PMID- 17508327
TI  - Aneurysms of pericallosal cerebral artery haemorrhage with consecutive psychosis.

PMID- 17508328
TI  - Aripiprazole for treatment of behavioural psychological symptoms of dementia.

PMID- 17508330
TI  - Abstracts of the IASSCS (International Association for the Study of Sexuality,
      Culture and Society) Conference, 27-29 June 2007, Lima, Peru.

PMID- 17508331
TI  - Do species converge during adaptation? A case study in Drosophila.
AB  - Adaptation to novel environments is a crucial theme in evolutionary biology,
      particularly because ex situ conservation forces populations to adapt to
      captivity. Here we analyze the evolution of life-history traits in two closely
      related species, Drosophila subobscura Collin and Drosophila madeirensis Monclus,
      during adaptation to the laboratory. Drosophila madeirensis, an endemic species
      from Madeira, is here shown to have less ability to adapt to the laboratory.
      Early fecundity was the only trait where this species showed a significant
      improvement with time. By comparison, D. subobscura improved in most traits, and
      its early fecundity increased faster than that of D. madeirensis. Our findings
      suggest that different species, even closely related ones, may adapt at different
      rates to the same environment.

PMID- 17508333
TI  - Evolutionary adaptation to freeze-thaw-growth cycles in Escherichia coli.
AB  - Fifteen populations of Escherichia coli were propagated for 150 freeze-thaw
      growth (FTG) cycles in order to study the phenotypic and genetic changes that
      evolve under these stressful conditions. Here we present the phenotypic
      differences between the evolved lines and their progenitors as measured by
      competition experiments and growth curves. Three FTG lines evolved from an
      ancestral strain that was previously used to start a long-term evolution
      experiment, while the other 12 FTG lines are derived from clones that had
      previously evolved for 20,000 generations at constant 37 degrees C. Competition
      experiments indicate that the former FTG group improved their mean fitness under
      the FTG regime by about 90% relative to their progenitor, while the latter FTG
      group gained on average about 60% relative to their own progenitors. These
      increases in fitness result from both improved survival during freezing and
      thawing and more rapid recovery to initiate exponential growth after thawing.
      This shorter lag phase is specific to recovery after freezing and thawing. Future
      work will seek to identify the mutations responsible for evolutionary adaptation
      to the FTG environment and use them to explore the physiological mechanisms that
      allow increased survival and more rapid recovery.

PMID- 17508332
TI  - Laboratory evolution of the migratory polymorphism in the sand cricket: combining
      physiology with quantitative genetics.
AB  - Predicting evolutionary change is the central goal of evolutionary biology
      because it is the primary means by which we can test evolutionary hypotheses. In
      this article, we analyze the pattern of evolutionary change in a laboratory
      population of the wing-dimorphic sand cricket Gryllus firmus resulting from
      relaxation of selection favoring the migratory (long-winged) morph. Based on a
      well-characterized trade-off between fecundity and flight capability, we predict
      that evolution in the laboratory environment should result in a reduction in the
      proportion of long-winged morphs. We also predict increased fecundity and reduced
      functionality and weight of the major flight muscles in long-winged females but
      little change in short-winged (flightless) females. Based on quantitative genetic
      theory, we predict that the regression equation describing the trade-off between
      ovary weight and weight of the major flight muscles will show a change in its
      intercept but not in its slope. Comparisons across generations verify all of
      these predictions. Further, using values of genetic parameters estimated from
      previous studies, we show that a quantitative genetic simulation model can
      account for not only the qualitative changes but also the evolutionary
      trajectory. These results demonstrate the power of combining quantitative genetic
      and physiological approaches for understanding the evolution of complex traits.

PMID- 17508334
TI  - Using experimental evolution to study the physiological mechanisms of desiccation
      resistance in Drosophila melanogaster.
AB  - Data from populations undergoing experimental evolution can be used to make
      comparisons between physiologically differentiated populations and to determine
      evolutionary trajectories. Comparisons of long-established laboratory populations
      of Drosophila melanogaster that are strongly differentiated with respect to
      desiccation resistance are used to test alternative hypotheses concerning the
      mechanisms that fruit flies use to survive bouts of extreme desiccation. This
      comparative study supports the hypothesis that, in at least one case, D.
      melanogaster can evolve increased resistance to desiccation by decreasing water
      loss rates and by increasing bulk water content but not by increasing metabolic
      water content or dehydration tolerance. While glycogen was involved in water
      storage, its primary role was in water binding, not the production of metabolic
      water. Measurement of the trajectories of these component mechanisms during
      selection for desiccation resistance is used to demonstrate that water loss rate
      quickly plateaus in response to selection, while water content continues to
      improve. This disparity reveals the value of studying evolutionary trajectories
      and the need for longer-term selection studies in evolutionary physiology.

PMID- 17508335
TI  - Experimental evolution of olfactory memory in Drosophila melanogaster.
AB  - In order to address the nature of genetic variation in learning performance, we
      investigated the response to classical olfactory conditioning in "high-learning"
      Drosophila melanogaster lines previously subject to selection for the ability to
      learn an association between the flavor of an oviposition medium and bitter
      taste. In a T-maze choice test, the seven high-learning lines were better at
      avoiding an odor previously associated with aversive mechanical shock than were
      five unselected "low-learning" lines originating from the same natural
      population. Thus, the evolved improvement in learning ability of high-learning
      lines generalized to another aversion learning task involving a different
      aversive stimulus (shock instead of bitter taste) and a different behavioral
      context than that used to impose selection. In this olfactory shock task, the
      high-learning lines showed improvements in the learning rate as well as in two
      forms of consolidated memory: anesthesia-resistant memory and long-term memory.
      Thus, genetic variation underlying the experimental evolution of learning
      performance in the high-learning lines affected several phases of memory
      formation in the course of olfactory aversive learning. However, the two forms of
      consolidated memory were negatively correlated among replicate high-learning
      lines, which is consistent with a recent hypothesis that these two forms of
      consolidated memory are antagonistic.

PMID- 17508336
TI  - An experimental evolutionary study on adaptation to temporally fluctuating pH in
      Escherichia coli.
AB  - In this study, we use the bacterium Escherichia coli to examine evolutionary
      responses to environmental acidity fluctuating temporally among pH 5.3, 6.3, 7.0,
      and 7.8 (5,000-15 nM [H(+)]). Two experimental protocols of temporal variation
      were used. One group (six replicate lines) of populations evolved for 2,000
      generations during exposure to a cycled regime fluctuating daily between pH 5.3
      and 7.8. The other group (also in six replicate lines) evolved during exposure
      for 2,000 generations to a randomly shifting regime fluctuating stochastically
      each day among pH 5.3, 6.3, 7.0, and 7.8. Adaptation to these fluctuating acidity
      regimes was measured as a change in fitness relative to the common ancestor by
      direct competition experiments in both constant and fluctuating pH regimes. For
      comparisons with constant pH evolution, a group evolved at a constant pH of 5.3
      and another group evolved at pH 7.8 were also tested. This study initiated the
      first long-term laboratory natural selection experiment on adaptation to variable
      acidity and addressed key questions concerning patterns of adaptation (trade
      offs, specialists, generalists, plasticity, transitions, and acclimation) in
      temporally fluctuating environments.

PMID- 17508337
TI  - Energizing an invertebrate embryo: bafilomycin-dependent respiration and the
      metabolic cost of proton pumping by the V-ATPase.
AB  - We examine herein the contribution of V-ATPase activity to the energy budget of
      aerobically developing embryos of Artemia franciscana and discuss the results in
      the context of quiescence under anoxia. (31)P-NMR analysis indicates that
      intracellular pH and NTP levels are unaffected by acute incubation of
      dechorionated embryos with the V-ATPase inhibitor, bafilomycin A(1). Bafilomycin
      A(1) also has no significant effect on oxygen consumption by isolated
      mitochondria. Taken together, these data indicate that bafilomycin does not
      affect energy-producing pathways in the developing embryo. However, the V-ATPase
      inhibitor exhibits a concentration-dependent inhibition of oxygen consumption in
      aerobic embryos. A conservative analysis of respirometric data indicates that
      proton pumping by the V-ATPase, and processes immediately dependent on this
      activity, constitutes approximately 31% of the aerobic energy budget of the
      preemergent embryo. Given the complete absence of detectable Na(+)K(+)-ATPase
      activity during the first hours of aerobic development, it is plausible that the
      V-ATPase is performing a role in both the acidification of intracellular
      compartments and the energization of plasma membranes. Importantly, the high
      metabolic cost associated with maintaining these diverse proton gradients
      requires that V-ATPase activity be downregulated under anoxia in order to attain
      the almost complete metabolic depression observed in the quiescent embryo.

PMID- 17508338
TI  - Seasonal variability in otariid energetics: implications for the effects of
      predators on localized prey resources.
AB  - Otariids, like other wild mammals, contend with a wide variety of energetic
      demands across seasons. However, due to the cryptic behaviors of this marine
      group, few studies have been able to examine longitudinal energetic costs or the
      potential impact of these costs on seasonal or annual prey requirements. Here we
      evaluated the changes in energy demand and intake of female California sea lions
      (Zalophus californianus) during reproductive (n=2 sea lions) and nonreproductive
      (n=3) periods. Monthly measurements included resting metabolic rate, blood
      hormone levels, body condition (blubber thickness and body mass), and caloric
      intake for adult sea lions throughout molting, late pregnancy, lactation, and
      postweaning. We found that maintenance energy demands decreased from 32.0 to 23.1
      MJ d(-1) before pupping, remaining stable at 19.4+/-0.6 MJ d(-1) during lactation
      and postweaning. Energy intake rates to meet these demands showed marked changes
      with activity level and the reproductive cycle, reaching a peak intake of 3.6
      times baseline levels during lactation. Translating this into prey demands, we
      find that 20,000 reproductively active females on San Nicolas Island rookeries
      would maximally require 4,950 metric tons of Pacific whiting during a month of
      the breeding season. This localized impact is reduced significantly with
      postbreeding dispersal and demonstrates the importance of considering spatial and
      temporal factors driving the energetic requirements of predators when designing
      marine protected areas.

PMID- 17508339
TI  - Searching for the physiological mechanism of density dependence: does
      corticosterone regulate tadpole responses to density?
AB  - Density-dependent population regulation is important in many natural populations,
      and in those populations, high population density is a likely stressor. In
      amphibians, previous laboratory studies with tadpoles suggest that
      corticosterone, the main glucocorticoid stress hormone, is one of the key
      regulators of density-dependent growth. To test this relationship in natural
      settings, we manipulated wood frog (Rana sylvatica) tadpole density at three
      levels in outdoor mesocosms and used a capture stress protocol to examine the
      hormonal stress response. In addition, we used the same capture protocol in six
      natural ponds (three high density and three low density). In the mesocosms, there
      was an increase in corticosterone levels in tadpoles following 1 h of confinement
      at weeks 1, 2, and 5. However, while tadpoles maintained at higher densities were
      smaller after metamorphosis, density did not alter mean levels of corticosterone
      obtained during confinement, and baseline levels of corticosterone did not differ
      between the densities. Similarly, in natural ponds, density did not correlate
      with baseline corticosterone or mean corticosterone levels obtained during
      confinement. We suggest that the physiological response to density may vary
      across the range of natural densities and that the role of corticosterone may be
      limited to periods of extreme high density, such as during pond-drying events.

PMID- 17508340
TI  - Intraspecific variability in the Basal metabolic rate: testing the food habits
      hypothesis.
AB  - Several competing hypotheses attempt to explain how environmental conditions
      affect mass-independent basal metabolic rate (BMR) in mammals. One of the most
      inclusive and yet debatable hypotheses is the one that associates BMR with food
      habits, including habitat productivity. These effects have been widely
      investigated at the interspecific level under the assumption that for any given
      species all traits are fixed. Consequently, the variation among individuals is
      largely ignored. Intraspecific analysis of physiological traits has the potential
      to compensate for many of the pitfalls associated with interspecific analyses
      and, thus, to be a useful approach for evaluating hypotheses regarding metabolic
      adaptation. In this study, we investigated the effects of food quality,
      availability, and predictability on the BMR of the leaf-eared mouse Phyllotis
      darwini. BMR was measured on freshly caught animals from the field, since they
      experience natural seasonal variations in environmental factors (and, hence,
      variations in habitat productivity) and diet quality. BMR was significantly
      correlated with the proportion of dietary plants and seeds. In addition, BMR was
      significantly correlated with monthly habitat productivity. Path analysis
      indicated that, in our study, habitat productivity was responsible for the
      observed changes in BMR, while diet per se had no effect on this variable.

PMID- 17508341
TI  - Comparison of admixture and association mapping in admixed families.
AB  - The family-based admixture mapping test (AMT) identifies disease-related genes
      using family data from admixed individuals with the disease of interest (cases).
      The cases' genotypes at a set of markers are used to infer their DNA ancestry as
      it varies in blocks along the chromosomes. The test compares the cases' inferred
      ancestries to those expected from their family histories. Deviation between
      observed and expected ancestries in a region suggests the presence of a disease
      gene. We use a likelihood-based development of the AMT to compare it with the
      transmission disequilibrium test (TDT) as applied to admixed populations. The two
      tests have a common framework but differ significantly when the disease locus is
      untyped. The TDT infers disease-locus genotypes using the markers with which it
      is in linkage disequilibrium (LD). In contrast, the AMT infers disease locus
      ancestries using those of its linked markers. Thus, TDT power depends on LD
      between disease and marker loci, while AMT power depends on the lengths of the
      ancestry blocks containing the disease locus. We compare the power of the two
      tests when applied to cases with descent from two ancestral populations. The AMT
      outperforms the TDT when case marker ancestries are correctly specified and LD
      between disease and marker loci is less than one-third its maximal value (Delta'
      < 1/3). However, the TDT performs better in the presence of uncertain marker
      ancestries, even for weak LD between disease and marker loci (Delta' = 0.1).
      These findings have implications for the design of studies using admixed
      populations.

PMID- 17508342
TI  - Effects of proximity and behavioral context on acoustic variation in the coo
      calls of Japanese macaques.
AB  - Acoustic features of coo calls in Japanese macaques (Macaca fuscata) show large
      and graded variation. To explore the relevance of acoustic variation in coo
      calls, I examined whether acoustic features differed by the caller's activity and
      proximity to group members. The subjects were five adult females from a wild,
      habituated group of Japanese macaques consisting of 23 individuals. Coo calls
      from the five females were recorded with their activity and proximity to group
      members. Acoustic features of 280 calls were measured with a sound spectrograph.
      Some of the acoustic variables differed by proximity but not by activity. The
      callers produced coo calls with larger frequency modulation and longer duration
      when they were far from group members compared to when they were near another
      member. The results suggest that Japanese macaques produce calls with more
      detectable and locatable features depending on the proximity to group members.

PMID- 17508343
TI  - Exploring causality via identification of SNPs or haplotypes responsible for a
      linkage signal.
AB  - In a small chromosomal region, a number of polymorphisms may be both linked to
      and associated with a disease. Distinguishing the potential causal sites from
      those indirectly associated due to linkage disequilibrium (LD) with a causal site
      is an important problem. This problem may be approached by determining which of
      the associations can explain the observed linkage signal. Recently, several
      methods have been proposed to aid in the identification of disease associated
      polymorphisms that may explain an observed linkage signal, using genotype data
      from affected sib pairs (ASPs) [Li et al. [2005] Am. J. Hum. Genet. 76:934-949;
      Sun et al. [2002] Am. J. Hum. Genet. 70:399-411]. These methods can be used to
      test the null hypothesis that a candidate single nucleotide polymorphism (SNP) is
      the sole causal variant in the region, or is in complete LD with the sole causal
      variant in the region. We extend variations of these methods to test for complete
      LD between a disease locus and haplotypes composed of two or more tightly linked
      candidate SNPs. We study properties of the proposed methods by simulation and
      apply them to type 1 diabetes data for ASPs and their parents at candidate SNP
      and microsatellite marker loci in the Insulin (INS) gene region.

PMID- 17508344
TI  - New cell surface markers for murine fetal hepatic stem cells identified through
      high density complementary DNA microarrays.
AB  - Isolation of hepatic stem cells from the adult liver (AL) has not yet been
      achieved due to the lack of specific cell surface markers. To identify new
      surface markers for hepatic stem cells, we analyzed differences in the gene
      expression profile of embryonic day (ED) 13.5 fetal liver stem/progenitor cells
      (FLSPC) versus AL by complementary DNA (cDNA) microarray technology. Using FLSPC
      purified to >90% by immunomagnetic selection for E-cadherin and high density
      (27k) mouse cDNA microarrays, we identified 474 genes that are more strongly
      expressed in FLSPC (FLSPC-up genes) and 818 genes that are more strongly
      expressed in AL (AL-up genes). The most highly overrepresented gene ontology (GO)
      categories for FLSPC-up genes are nucleus, cellular proliferation, and cell cycle
      control. AL-up genes are overrepresented for genes in metabolic pathways for
      specific hepatic functions. We identified 24 FLSPC-up gene surface markers and 69
      AL-up gene surface markers. Western blot studies confirmed the expression of the
      FLSPC-up gene neighbor of Punc E11 (Nope) in fetal liver, but expression was not
      detectable in AL. Immunohistochemistry, confocal microscopy, and fluorescence
      activated cell sorting (FACS) analysis of fetal liver demonstrated that Nope is
      specifically expressed on the surface of FLSPC within the fetal liver.
      CONCLUSION: This is the first microarray study to analyze the specific gene
      expression profile of purified murine FLSPC. Our analysis identified 24
      new/potential cell surface markers for murine fetal hepatic stem cells, of which
      Nope may be particularly useful in future studies to identify, characterize and
      isolate hepatic stem cells from the AL.

PMID- 17508349
TI  - A new oxocarbon C12O6 via highly strained benzyne intermediates.

PMID- 17508354
TI  - A hierarchical model for estimating significance levels of non-parametric linkage
      statistics for large pedigrees.
AB  - The significance level of a non-parametric linkage (NPL) statistic is often found
      by simulation since the distribution of the test statistic is complex and
      unknown. Ideally, simulation occurs by randomly assigning founder genotypes and
      then simulating meiotic events for the descendants in the pedigree, commonly
      referred to as 'gene dropping'. The missing data pattern in the original
      pedigree, including lack of phase information (due to unordered genotypes), is
      then imposed on the simulated pedigree. However, this approach is usually
      computationally infeasible for larger pedigrees which require Markov chain Monte
      Carlo (MCMC) techniques to calculate the statistic, as an additional MCMC run is
      required to estimate the statistic for each gene drop. In this work, we propose a
      novel method to estimate the significance level of the NPL statistic in large
      pedigrees. This is accomplished by constructing a hierarchical model, which
      allows estimation of the NPL statistic variability via separate estimation of the
      Markov chain and gene dropping variability. The significance level is estimated
      by fitting a parametric model to the statistic and using the method of moments to
      obtain parameter estimates. In a simulation study we found our hierarchical model
      estimates to be very close to the gold standard empirical estimates, and offer
      substantial improvements over the existing conservative method used by the
      software SimWalk2. The estimation procedure significantly reduces the
      computational time relative to the ideal empirical estimate, allowing for an
      accurate estimate of the significance level in a more manageable amount of time.

PMID- 17508355
TI  - Dopaminergic candidate genes in Tourette syndrome: association between tic
      severity and 3' UTR polymorphism of the dopamine transporter gene.
AB  - Multiple evidence suggests an involvement of the dopamine neurotransmitter system
      in Tourette syndrome (TS). Therefore, dopaminergic candidate genes are in the
      center of genetic association analyses of TS. In this study, 103 TS patients and
      their parents have been characterized for different dopamine-related
      polymorphisms including the 48 bp variable number of tandem repeats (VNTR) of the
      dopamine D4 receptor (DRD4) gene, the 40 bp VNTR of the dopamine transporter
      (DAT1, SLC6A3) gene and the Val158Met polymorphism of the catechol-O
      methyltransferase (COMT) gene. In addition, the 120 bp duplication and three
      single nucleotide polymorphisms (SNPs) were assessed in the promoter region of
      the DRD4 gene. The -616G allele and the 2-G-A-C haplotype (i.e., the 2-repeat
      form of the 120 bp sequence approximately -616G approximately -615A approximately
      -521C combination) were preferentially transmitted, however, these results did
      not remain significant after correction for multiple testing. Case-control
      analyses have also been carried out, resulting in negative findings. On the other
      hand, using a dimensional approach, the DAT1 40 bp VNTR showed an association
      with the peak tic-severity as measured by the Yale Global Tic Severity Scale.
      Patients with at least one copy of the 9-repeat allele had significantly more
      severe symptoms than individuals with the homozygous 10/10 genotype (P = 0.002).
      In summary, allele frequencies did not differ between cases and controls, but
      DAT1 genotype accounted for variations of tic severity within the TS group.

PMID- 17508356
TI  - Actin polymerization modulates CD44 surface expression, MMP-9 activation, and
      osteoclast function.
AB  - CD44 and MMP-9 are implicated in cell migration. In the current study, we tested
      the hypothesis that actin polymerization is critical for CD44 surface expression
      and MMP-9 activity on the cell surface. To understand the underlying molecular
      mechanisms involved in CD44 surface expression and MMP-9 activity on the cell
      surface, osteoclasts were treated with bisphosphonate (BP) alendronate,
      cytochalasin D (Cyt D), and a broad-spectrum MMP inhibitor (GM6001). BP has been
      reported to block the mevalonate pathway, thereby preventing prenylation of small
      GTPase signaling required for actin cytoskeleton modulation. We show in this
      study that osteoclasts secrete CD44 and MMP-9 into the resorption bay during
      migration and bone resorption. Results indicate that actin polymerization is
      critical for CD44 surface expression and osteoclast function. In particular, the
      surface expression of CD44 and the membrane activity of MMP-9 are reduced in
      osteoclasts treated with alendronate and Cyt D despite the membrane levels of MMP
      9 being unaffected. Although GM6001 blocked MMP-9 activity, osteoclast migration,
      and bone resorption, the surface levels of CD44 were unaffected. We suggest that
      the surface expression of CD44 requires actin polymerization. Disruption of
      podosome and actin ring structures by Cyt D and alendronate not only resulted in
      reduced localization of MMP-9 in these structures but also in osteoclast
      migration and bone resorption. These results suggest that inhibition of actin
      polymerization by alendronate and Cyt D is effective in blocking CD44/MMP-9
      complex formation on the cell surface, secretion of active form of MMP-9, and
      osteoclast migration. CD44/MMP-9 complex formation may signify a unique motility
      enhancing signal in osteoclast function.

PMID- 17508357
TI  - Insulin receptor substrate 1 (IRS-1) plays a unique role in normal epidermal
      physiology.
AB  - Insulin receptor substrate (IRS) proteins play a central role in insulin
      signaling. Previously we have demonstrated that insulin is essential for normal
      skin development and function. In the present study we investigated the
      involvement of the IRS-1 and IRS-2 proteins in skin physiology and in mediating
      insulin action in skin. For this purpose we have investigated the effects of
      inactivation of each of the IRSs on skin, studying skin sections and primary skin
      cells derived from IRS-1 or IRS-2 null mice. We have demonstrated that while the
      skin of the IRS-2 null mice appeared normal, the skin of the IRS-1 null mice was
      thinner and translucent. Histological analysis revealed that the thinning of the
      IRS-1 null skin was a consequence of the thinning of the spinous compartment,
      consisting of fewer layers. Proliferation of the IRS-1 and IRS-2 null skin
      epidermal cells was normal. However, the differentiation process of the IRS-1
      skin and skin cells was impaired. There was a marked decrease in the induction of
      the expression of K1, the marker of advanced stages of skin differentiation. In
      contrary, IRS-2 inactivation had no effects on skin differentiation. In
      conclusion, we have shown for the first time that IRS-1 but not IRS-2 has an
      effect on skin formation and development, being one of the main activators of the
      differentiation process in skin keratinocytes. Furthermore, we suggest that IRS-1
      and IRS-2 have distinct roles in skin physiology.

PMID- 17508358
TI  - A novel method to express SNP-based genetic heterogeneity, Psi, and its use to
      measure linkage disequilibrium for multiple SNPs, D(g), and to estimate absolute
      maximum of haplotype frequency.
AB  - Single nucleotide polymorphisms (SNPs) are important markers to investigate
      genetic heterogeneity of population and to perform linkage disequilibrium (LD)
      mapping. We propose a new method, Psi, to express frequency of 2(N(s)) haplotypes
      for N(s) di-allelic SNPs. Using the new expression of haplotype frequency, we
      propose a novel measure of LD, D(g), not only for SNP pairs but also for multiple
      markers. The values of D(g) for SNP pairs were revealed to be similar to values
      of conventional pairwise LD indices, D' and r(2), and it was revealed that D(g)
      quantitated components of LD that were not measured by conventional LD indices
      for SNP pairs. Also we propose a distinct method, D(g)-based absolute estimation,
      to infer the absolute maximum estimates of haplotype frequency. The result of the
      D(g)-based absolute estimation of haplotype frequency for SNP pairs were compared
      with the conventional expectation-maximization (EM) algorithm and reported that
      the new method gave better inference than the EM algorithm which converged
      infrequently to a local extreme.

PMID- 17508359
TI  - Power of genome-wide association studies in the presence of interacting loci.
AB  - Though multiple interacting loci are likely involved in the etiology of complex
      diseases, early genome-wide association studies (GWAS) have depended on the
      detection of the marginal effects of each locus. Here, we evaluate the power of
      GWAS in the presence of two linked and potentially associated causal loci for
      several models of interaction between them and find that interacting loci may
      give rise to marginal relative risks that are not generally considered in a one
      locus model. To derive power under realistic situations, we use empirical data
      generated by the HapMap ENCODE project for both allele frequencies and linkage
      disequilibrium (LD) structure. The power is also evaluated in situations where
      the causal single nucleotide polymorphisms (SNPs) may not be genotyped, but
      rather detected by proxy using a SNP in LD. A common simplification for such
      power computations assumes that the sample size necessary to detect the effect at
      the tSNP is the sample size necessary to detect the causal locus directly divided
      by the LD measure r(2) between the two. This assumption, which we call the
      "proportionality assumption", is a simplification of the many factors that
      contribute to the strength of association at a marker, and has recently been
      criticized as unreasonable (Terwilliger and Hiekkalinna [2006] Eur J Hum Genet
      14(4):426-437), in particular in the presence of interacting and associated loci.
      We find that this assumption does not introduce much error in single locus models
      of disease, but may do so in so in certain two-locus models.

PMID- 17508360
TI  - Transient receptor potential vanilloid 1 activation induces inflammatory cytokine
      release in corneal epithelium through MAPK signaling.
AB  - In certain epithelial tissues, activation of transient receptor potential (TRP)
      vanilloid subtype 1 (TRPV1) by noxious stimuli induces pro-inflammatory cytokine
      release, which helps to mitigate the challenge. While the corneal epithelium
      elicits such responses to a variety of challenges, it remains unknown whether
      TRPV1 mediates pro-inflammatory cytokine secretion. Accordingly, we probed for
      TRPV1 expression and function in human (HCEC) and rabbit corneal epithelial cell
      (RCEC) lines, in their primary counterparts, and in human and mouse corneal
      epithelium in situ. Cell membrane and perinuclear TRPV1 expression was detected
      in all preparations and its identity verified by Western blot analysis. Capsaicin
      (CAP) (1-10 microM) increased nonselective cation channel whole cell currents
      (2.5-fold +/- 0.5-fold between -60 and 130 mV), resulting in calcium transients
      that were fully blocked by the TRPV1 antagonists capsazepine (CPZ) and ruthenium
      red, or removal of extracellular calcium. Another signaling event involved
      transient activation of global mitogen-activated protein kinase (MAPK)
      superfamily, which was followed by up to 3.3- and 9-fold increases in
      interleukins (IL)-6 and -8 release, respectively. Such increases in inflammatory
      mediators' release were suppressed by exposure to CPZ or MAPK inhibitors, or
      removal of Ca2+. Taken together, TRPV1 receptors may play a role in mediating
      corneal epithelial inflammatory mediator secretion and subsequent hyperalgesia.

PMID- 17508361
TI  - Molecular organization and in vivo function of the cytoskeleton of amphibian
      erythrocytes.
AB  - One prominent cytoskeletal feature of non-mammalian vertebrate erythrocytes is
      the marginal band (MB), composed of microtubules. However, there have been
      several reports of MB-associated F-actin. We have further investigated the
      function of MB-associated F-actin, using newt erythrocytes having large, thick
      MBs. Confocal microscopy revealed a distinctive band of F-actin colocalizing
      point- by-point with MB microtubules. Furthermore, the F-actin band was present
      in isolated elliptical MBs, but absent in membrane skeletons lacking MBs. F-actin
      depolymerizing agents did not affect F-actin band integrity in isolated MBs,
      indicating its non-dynamic state. However, exposure to elastase resulted in F
      actin removal and MB circularization. These results provide evidence of a strong
      association of F-actin with MB microtubules in mature ellipsoidal erythrocytes.
      To assess the true extent of mechanical stress on the cytoskeleton, erythrocytes
      were observed by video microscopy during flow in vivo. Moving with long axis
      parallel to flow direction, cells underwent reversible shape distortion as they
      collided vigorously with other erythrocytes and vessel walls. In addition, cells
      twisted into figure-8 shapes, a cytoskeletal property that may provide
      physiological advantages during flow. Our results, together with those of others,
      yield a consistent picture in which developing erythrocytes undergo transition
      from spheroids to immature discoids to mature ellipsoids. The causal step in
      discoid formation is biogenesis of circular MBs with sufficient flexural rigidity
      to determine cell shape. F-actin binding to MB microtubules then creates a
      composite system, enhancing flexural rigidity to produce and maintain ellipsoidal
      shape during the physical challenges of blood flow in vivo.

PMID- 17508362
TI  - Synthesis, structure, and electrochemical properties of sterically protected
      molybdenum trihydride redox pairs: a paramagnetic "stretched" dihydrogen complex?
AB  - Complexes [MoCp(#)(PMe(3))(2)H(3)] (Cp(#)=1,2,4-C(5)H(2)tBu(3), 2 a; C(5)HiPr(4),
      2 b) have been synthesized from the corresponding compounds [MoCp(#)Cl(4)] (1 a,
      1 b) and fully characterized, including by X-ray crystallography and by a neutron
      diffraction study for 2 a. Protonation of 2 a led to complex [Mo(1,2,4
      C(5)H(2)tBu(3))(PMe(3))(2)H(4)](+) (3 a) in THF and to [Mo(1,2,4
      C(5)H(2)tBu(3))(PMe(3))(2)(MeCN)H(2)](+) (4 a) in MeCN. Complex 4 b analogously
      derives from protonation of 2 b in MeCN, whereas the tetrahydride complex 3 b is
      unstable. One-electron oxidation of 2 a and 2 b by [FeCp(2)]PF(6) produces the
      EPR-active 17-electron complexes 2 a(+) and 2 b(+). The former is thermally more
      stable than the latter and could be crystallographically characterized as the
      PF(6) (-) salt by X-ray diffraction, providing evidence for the presence of a
      stretched dihydrogen ligand (H...H=1.36(6) angstroms). Controlled thermal
      decomposition of 2 a(+) yielded the product of H(2) elimination, the 15-electron
      monohydride complex [Mo(1,2,4-C(5)H(2)tBu(3))(PMe(3))(2)H]PF(6) (5 a), which was
      characterized by X-ray crystallography and by EPR spectroscopy at liquid He
      temperature. The compound establishes an equilibrium with the solvent adduct in
      THF. An electrochemical study by cyclic voltammetry provides further evidence for
      a rapid H(2) elimination process from the 17-electron complexes. In contrast to
      the previously investigated [MoCp*(dppe)H(3)](+) system (dppe=1,2
      bis(diphenylphosphino)ethane; Cp*=pentamethylcyclopentadienyl), the decomposition
      of 2 a(+) by H(2) substitution with a solvent molecule appears to follow a
      dissociative pathway in MeCN.

PMID- 17508363
TI  - Total synthesis of five thapsigargins: guaianolide natural products exhibiting
      sub-nanomolar SERCA inhibition.
AB  - Herein we describe the total synthesis of five guaianolide natural products:
      thapsigargin, thapsivillosin C, thapsivillosin F, trilobolide and nortrilobolide.
      Prodrug derivatives of thapsigargin have shown selective in vivo cytotoxicity
      against prostate tumours and the need for further investigation of this
      phenomenon highlights the importance of these total syntheses. The first absolute
      stereochemical assignment of thapsivillosin C is also delineated.

PMID- 17508364
TI  - Sugar-assisted ligation for the synthesis of glycopeptides.
AB  - Chemical synthesis of glycoproteins from readily available materials is a
      powerful method for obtaining a pure product with full control of its atomic
      structure. Sugar-assisted ligation (SAL) is an emerging approach that allows the
      synthesis of a large glycopeptide from two unprotected fragments. Contrary to
      other ligation methods that are limited to the use of a cysteine residue or
      depend on external auxiliary, SAL takes advantage of the existing sugars in
      glycopeptides to promote proximity between the two peptides to facilitate an
      amide bond formation.

PMID- 17508365
TI  - Charge-transfer emission involving three-coordinate organoboron: V-shape versus U
      shape and impact of the spacer on dual emission and fluorescent sensing.
AB  - New V-shaped bifunctional organosilicon compounds that contain an electron
      acceptor, B(Mes)2, and an electron donor, N(1-naph)Ph, with the formulae Ph2Si{p
      C6H4B(Mes)2}{p-C6H4N(1-naph)ph)} (1), Ph2Si{p-C6H4(Mes)2}{p-biphenyl-N(1-naph)ph}
      (2), and Si{p-C6H4B(Mes)2}2{p-C6H4N(1-naph)ph)}2 (3) have been synthesized as
      model compounds for the investigation of through-space charge-transfer emission
      involving triarylboron and triarylamino centers. The photophysical properties of
      the new bifunctional organosilicon compounds are compared to two U-shaped
      compounds sBN and BN in which the boron acceptor and the amino donor groups are
      linked together by a rigid 1,10-naphthyl group. The results of our investigation
      establish that dual emission pathways, namely through-space donor-acceptor charge
      transfer and pi-pi* transitions coexist in the V-shaped molecules 1-3, while
      charge transfer emission is dominant in the U-shaped molecules. It is found that
      depending on the geometry of the linker and the BN separation distance, the
      compound either displays dual emission bands simultaneously or single emission
      band. In addition, the dual emission pathways in these molecules can be
      selectively switched on or off by using fluoride ions. The sensitivity of
      response to fluoride ions by these molecules is also found to be highly dependent
      on the geometry of the linker and the BN separation distance. The V-shaped
      molecules are found to be "turn-on" sensors to fluorides with a much higher
      sensitivity than the U-shaped molecules.

PMID- 17508366
TI  - The anhydride route to Group 15/16 ligands in oligomeric and polymeric
      environments: from metal complexes to supraionic chemistry.
AB  - The aim of this paper is to introduce a synthetic concept suitable for the
      preparation of a broad variety of compounds. The so-called anhydride route (in
      this article the term anhydride is used for compounds derived from corresponding
      acids by formal loss of H2O, H2S and H2Se) has so far led to a range of unusual
      Group 15/16 ligands in oligomeric and polymeric environments. Commonly, reactions
      of neutral precursor molecules, for example, [{RP(S)(mu-S)}2] (R=4-anisyl)
      Lawesson's reagent or [{PhP(Se)(mu-Se)}2] Woollins's reagent and metal salts are
      performed to result in novel coordination compounds in which ligands and metal
      atoms form coordination oligomers and polymers. An attempt is made to relate the
      outcome of the investigations to the type of metal used. By relating the strength
      of ionic interactions, which correspond to metal-donor distances, to phenomena
      observed in the solid-state structures, an aspect of supraionic chemistry is
      described. Chemistry of and beyond novel Group 15/16 anions is further discussed
      using a novel approach in coordination chemistry where the chemical nature of
      ligands is unknown prior to the experiment despite the use of a range of similar
      starting materials.

PMID- 17508367
TI  - Specifically immobilised aldo/keto reductase AKR1A1 shows a dramatic increase in
      activity relative to the randomly immobilised enzyme.
AB  - The difference between site-specific and random immobilisation of the aldo/keto
      reductase AKR1A1 was explored. AKR1A1 was recombinantly expressed as a thioester
      by the intein strategy. The thioester was selectively modified with a biotin
      label by the expressed protein ligation method, and subsequent immobilisation on
      streptavidin templates was performed. Adsorption of wild-type AKR1A1 to
      streptavidin templates and of biotinylated AKR1A1 to uncoated templates was used
      to study randomly immobilised enzymes. Investigation of the kinetic parameters
      revealed remarkably improved activity for the site-specifically immobilised
      enzyme, which was comparable to that of the wild-type enzyme in solution and 60
      300-fold greater than that of the randomly immobilized enzymes. Furthermore, the
      enzyme was surprisingly stable. No loss of activity was observed for over a week,
      and even after 50 days more than 35% of activity was maintained.

PMID- 17508368
TI  - 1,2-Mannobioside mimic: synthesis, DC-SIGN interaction by NMR and docking, and
      antiviral activity.
AB  - The design and preparation of carbohydrate ligands for DC-SIGN is a topic of high
      interest because of the role played by this C-type lectin in immunity and
      infection processes. The low chemical stability of carbohydrates against
      enzymatic hydrolysis by glycosylases has stimulated the search for new
      alternatives more stable in vivo. Herein, we present a good alternative for a DC
      SIGN ligand based on a mannobioside mimic with a higher enzymatic stability than
      the corresponding disaccharide. NMR and docking studies have been performed to
      study the interaction of this mimic with DC-SIGN in solution demonstrating that
      this pseudomannobioside is a good ligand for this lectin. In vitro studies using
      an infection model with Ebola pseudotyped virus demonstrates that this compound
      presents an antiviral activity even better than the corresponding disaccharide
      and could be an interesting ligand to prepare multivalent systems with higher
      affinities for DC-SIGN with potential biomedical applications.

PMID- 17508369
TI  - Microwave-assisted transition-metal-catalyzed synthesis of N-shifted and ring
      expanded buflavine analogues.
AB  - Two novel and efficient strategies for the synthesis of hitherto unknown N
      shifted and ring-expanded buflavine analogues are presented. Construction of the
      medium-sized ring system of the title molecules, a difficult task due to the high
      activation energy needed for the ring-closure with the additional rigidity
      imposed by the biaryl skeleton, was achieved by using Suzuki-Miyaura biaryl
      coupling and a ring-closing metathesis reaction as the key steps. The combination
      of a second-generation Grubbs catalyst and microwave irradiation proved to be
      highly useful in generating the otherwise difficult to obtain medium-sized ring
      system of the buflavine analogues.

PMID- 17508370
TI  - Cucurbit[8]uril/cucurbit[7]uril controlled off/on fluorescence of the
      acridizinium and 9-aminoacridizinium cations in aqueous solution.
AB  - The blue fluorescence of acridizinium bromide (ADZ+) and the green fluorescence
      of 9-aminoacridizinium bromide (AADZ+) in aqueous solutions can be almost
      entirely switched off upon the double inclusion of these guests in the cavity of
      cucurbit[8]uril (CB[8]) owing to the formation of a nonfluorescent, noncovalent
      dimer complex, and then fluorescence can be effectively restored by adding
      cucurbit[7]uril (CB[7]) to the complex because it competitively extracts the
      fluorophores out of the CB[8] cavity.

PMID- 17508371
TI  - Electrostatic attachment of gold and poly(lactic acid) nanoparticles onto omega
      aminoalkanoic acid self-assembled monolayers on 316L stainless steel.
AB  - The assembly of poly(lactic acid) (PLA) nanoparticles on a 12-aminodecanoic acid
      (ADA) self-assembled monolayer (SAM) is described. Assembly is accomplished
      through electrostatic interactions between the positively charged SAM and the
      negatively charged PLA nanoparticles. The strategy used involves two steps in
      which a preliminary electrochemical coating of the ADA SAM is followed by a
      second step that involves immersing the SAM in a solution containing gold or PLA
      nanoparticles. The SAM was characterized by using cyclic voltammetry (CV), X-ray
      photoelectron spectroscopy (XPS), FTIR spectroscopy, and contact angle
      measurements, whereas scanning electron microscopy (SEM) was used to image the
      nanoparticles after electrostatic attachment was achieved. We found that the
      surface coverage of the nanoparticles could be controlled by modulating the
      electrostatic interactions between the negatively charged particles and the
      positively charged SAM surface by varying the pH of the nanoparticle solution,
      the immersion time, and the number of cyclic voltammetry scans under which the
      SAM was formed.

PMID- 17508372
TI  - Synthesis and biological evaluation of phosphono analogues of capsular
      polysaccharide fragments from Neisseria meningitidis A.
AB  - Neisseria meningitidis type A (MenA) is a Gram-negative encapsulated bacterium
      that may cause explosive epidemics of meningitis, especially in the sub-Saharan
      region of Africa. The development and manufacture of an efficient glycoconjugate
      vaccine against Neisseria meningitidis A is greatly hampered by the poor
      hydrolytic stability of its capsular polysaccharide, which is made up of (1-->6)
      linked 2-acetamido-2-deoxy-alpha-D-mannopyranosyl phosphate repeating units.
      Since this chemical lability is a product of the inherent instability of the
      phosphodiester bridges, here we report the synthesis of phosphonoester-linked
      oligomers of N-acetyl mannosamine as candidates for stabilised analogues of the
      corresponding phosphate-bridged saccharides. The installation of each
      interglycosidic phosphonoester linkage was achieved by Mitsunobu coupling of a
      glycosyl C-phosphonate building block with the 6-OH moiety of a mannosaminyl
      residue. Each of the synthesised compounds contains an O-linked aminopropyl
      spacer at its reducing end (alpha- or beta-oriented) to allow for protein
      conjugation. The relative affinities of the synthetic molecules were investigated
      by a competitive ELISA assay and showed that a human polyclonal anti-MenA serum
      can recognise both the phosphonoester-bridged fragments 1-3 and their monomeric
      subunits, glycosides 20 and 21. Moreover, the biological results suggest that the
      abilities of these compounds to inhibit the binding of a specific antibody to
      MenA polysaccharide are dependent on the chain lengths of the molecules, but
      independent on the orientations of the anomeric linkers.

PMID- 17508373
TI  - Intramolecular hydroamination with homogeneous zinc catalysts: evaluation of
      substituent effects in N,N'-disubstituted aminotroponiminate zinc complexes.
AB  - A series of symmetrical and unsymmetrical N,N'-disubstituted aminotroponimines
      (ATIHs) have been prepared. Substituents ranging from linear to cyclic alkyl
      groups, chelating ethers, and aryl groups were employed. The corresponding
      aminotroponiminate zinc complexes were then synthesized and characterized by a
      number of techniques, including by X-ray crystallography. Herein we report on the
      investigations into their activity in the intramolecular hydroamination of
      nonactivated alkenes. We also demonstrate that complexes bearing ligands with
      cyclic alkyl groups show superior activity in a number of selected reactions with
      functionalized aminoalkenes.

PMID- 17508374
TI  - Preparation of a polymer-supported fluorene-based receptor for quantitative and
      efficient binding of silver cations.
AB  - We have designed and synthesized a polymer-supported material in which a
      versatile fluorene-p-xylene-based receptor is woven onto the backbone of
      polystyrene. This polymer-supported receptor adopts a pi-prismand-like
      conformation through a simple C--C bond rotation that results in the quantitative
      binding of a single silver cation per receptor site with a remarkable efficiency
      that exceeds the binding abilities of the well-known tris[2.2.2]-p-cyclophane (or
      pi prismand) by at least a factor of 100. More importantly, the binding event can
      be readily monitored by 1H NMR spectroscopy, as well as by a more sensitive
      emission spectroscopic technique in which the quenching of fluorescence of the
      receptor moiety is quantitatively related to the binding of silver cations.

PMID- 17508375
TI  - Hydrolysis of dinuclear ruthenium complexes [{CpRu(PPh3)2}2(micro,eta(1:1)
      L)][CF3SO3]2 (L=P4, P4S3): simple access to metal complexes of P2H4 and PH2SH.
AB  - The reaction of [CpRu(PPh(3))(2)Cl] (1) with half an equivalent of P(4) or
      P(4)S(3) in the presence of AgCF(3)SO(3) as chloride scavenger affords the stable
      dimetal complexes [{CpRu(PPh(3))(2)}(2)(micro,eta(1:1)-P(4))][CF(3)SO(3)](2).3
      CH(2)Cl(2) (2) and [{CpRu(PPh(3))(2)}(2)(micro,eta(1:1)-P(apical)-P(basal)
      P(4)S(3))][CF(3)SO(3)](2).0.5 C(7)H(8) (3), in which the tetrahedral P(4) and
      mixed-cage P(4)S(3) molecules are respectively bound to two CpRu(PPh(3))(2)
      fragments through two phosphorus atoms. The coordinated cage molecules, at
      variance with the free ligands, readily react with an excess of water in THF
      under mild conditions. Among the hydrolysis products, the new, remarkably stable
      complexes [{CpRu(PPh(3))(2)}(2)(micro,eta(1:1)-P(2)H(4))][CF(3)SO(3)](2) (4) and
      [CpRu(PPh(3))(2)(eta(1)-PH(2)SH)]CF(3)SO(3) (8) were isolated. In the former,
      diphosphane, P(2)H(4), is coordinated to two CpRu(PPh(3))(2) fragments, and in
      the latter thiophosphinous acid, H(2)PSH, is coordinated to the metal centre
      through the phosphorus atom. All compounds were characterised by elemental
      analyses and IR and NMR spectroscopy. The crystal structures of 2, 3, 4 and 8
      were determined by X-ray diffraction.

PMID- 17508376
TI  - Towards nanotubular structures with large voids: dynamic heteroleptic
      oligophenanthroline metallonanoscaffolds and their solution-state properties.
AB  - The assembly of a rigid macrocycle with two exotopic phenanthroline binding sites
      in combination with linear bis- or trisphenanthrolines and copper(I) ions is used
      to generate nanoscale double and triple deckers, the latter showing a tubular
      structure. With supramolecular chemistry expanding to dynamic, large cavity,
      nanoscale structures, it becomes increasingly important to use robust assembly
      protocols as well as reliable characterization techniques. To fully elucidate and
      to describe the dynamic nature of metallonanoscaffolds with large voids, we
      applied a battery of both direct and indirect solution-state characterization
      methods. These methods along with the conventional direct methods provide a very
      useful tool for characterizing tubular nanoscaffold aggregates.

PMID- 17508377
TI  - Novel transition-metal-free heterogeneous epoxidation catalysts discovered by
      means of high-throughput experimentation.
AB  - Various transition-metal-free oxides have been studied as catalysts for the
      epoxidation of cyclooctene with hydrogen peroxide by means of high-throughput
      experimentation. Different boron, aluminium, and gallium oxides were prepared
      according to various synthesis methods. A number of pure aluminium and gallium
      oxides showed very good catalytic performances, while the results obtained with
      boron oxides or mixed oxides were less positive. The best results were obtained
      with a gallium oxide catalyst, which gave an epoxide yield of 71 % and a
      selectivity of 99 % after reaction for 4 h at 80 degrees C. Gallium oxides had
      not been reported previously as active epoxidation catalysts. The use of high
      throughput experimentation proved useful both for discovering new active
      catalysts and for identifying a number of relationships between the synthesis
      conditions and the catalytic properties of the transition-metal-free oxides.

PMID- 17508378
TI  - Circular dichroism and conformational dynamics of cephams and their carba and oxa
      analogues.
AB  - The biological activity of bicyclic beta-lactam antibiotics depends strongly on
      the absolute configuration of the bridgehead carbon atom. Frelek and co-workers
      proposed an empirical helicity rule relating the configuration of the bridgehead
      carbon atom to the sign of the 220 nm band in the electronic circular dichroism
      (CD) spectrum of beta-lactams. Here we use synthetic organic chemistry, CD
      spectroscopy, and time-dependent density functional theory (TDDFT) to investigate
      the validity of this structure-property relationship for eight model compounds.
      For conformationally flexible beta-lactams, substantial thermal effects are found
      which must be included in calculations. To this end, we combine TDDFT
      calculations of CD with full quantum-mechanical Born-Oppenheimer molecular
      dynamics (MD) simulations for the first time. The CD spectra are sampled with
      ground-state density functional trajectories of up to 60 ps. The MD simulations
      show a surprisingly high sensitivity of the CD to the molecular conformation. On
      the other hand, the relation between CD and thermally averaged structural
      parameters is much less complex. While the helicity rule does not seem to hold
      for individual conformers, it is confirmed by the calculations for seven out of
      eight systems studied if thermally averaged CD spectra and structures are
      considered. Since thermal effects on CD can be larger than typical inherent
      inaccuracies of TDDFT, our results emphasize the need for a systematic treatment
      of conformational dynamics in CD calculations even for moderately flexible
      systems. Temperature-dependent CD measurements are very useful for this purpose.
      Our results also suggest that CD spectroscopy may be used as a sensitive probe of
      conformational dynamics if combined with electronic structure calculations.

PMID- 17508380
TI  - Copper halide-bridged ruthenium telluride carbonyl complexes: discovery of the
      semiconducting cluster chain polymer
      {[PPh4]2[Te2Ru4(CO)10Cu4Br2Cl2].THF}infinity.
AB  - A new series of Te-Ru-Cu carbonyl complexes was prepared by the reaction of
      K(2)TeO(3) with [Ru(3)(CO)(12)] in MeOH followed by treatment with PPh(4)X (X=Br,
      Cl) and [Cu(MeCN)(4)]BF(4) or CuX (X=Br, Cl) in MeCN. When the reaction mixture
      of K(2)TeO(3) and [Ru(3)(CO)(12)] was first treated with PPh(4)X followed by the
      addition of [Cu(MeCN)(4)]BF(4), doubly CuX-bridged Te(2)Ru(4)-based octahedral
      clusters [PPh(4)](2)[Te(2)Ru(4)(CO)(10)Cu(2)X(2)] (X=Br, [PPh(4)](2)[1]; X=Cl,
      [PPh(4)](2)[2]) were obtained. When the reaction mixture of K(2)TeO(3) and
      [Ru(3)(CO)(12)] was treated with PPh(4)X (X=Br, Cl) followed by the addition of
      CuX (X=Br, Cl), three different types of CuX-bridged Te-Ru carbonyl clusters were
      obtained. While the addition of PPh(4)Br or PPh(4)Cl followed by CuBr produced
      the doubly CuBr-bridged cluster 1, the addition of PPh(4)Cl followed by CuCl led
      to the formation of the Cu(4)Cl(2)-bridged bis-TeRu(5)-based octahedral cluster
      compound [PPh(4)](2)[{TeRu(5)(CO)(14)}(2)Cu(4)Cl(2)] ([PPh(4)](2)[3]). On the
      other hand, when the reaction mixture of K(2)TeO(3) and [Ru(3)(CO)(12)] was
      treated with PPh(4)Br followed by the addition of CuCl, the Cu(Br)CuCl-bridged
      Te(2)Ru(4)-based octahedral cluster chain polymer
      {[PPh(4)](2)(Te(2)Ru(4)(CO)(10)Cu(4)Br(2)Cl(2)).THF}(infinity)
      ({[PPh(4)](2)[4].THF}(infinity)) was produced. The chain polymer
      {[PPh(4)](2)[4].THF}(infinity) is the first ternary Te-Ru-Cu cluster and shows
      semiconducting behavior with a small energy gap of about 0.37 eV. It can be
      rationalized as resulting from aggregation of doubly CuX-bridged clusters 1 and 2
      with two equivalents of CuCl or CuBr, respectively. The nature of clusters 1-4
      and the formation and semiconducting properties of the polymer of 4 were further
      examined by molecular orbital calculations at the B3LYP level of density
      functional theory.

PMID- 17508379
TI  - Multifunctionalization of dendrimers through orthogonal transformations.
AB  - A straightforward methodology for the synthesis of multifunctionalized dendrimers
      that is based on an orthogonal functionalization strategy has been developed.
      Polyamide-based dendrimers that possess both a single aldehyde and a single azide
      moiety on their periphery have been synthesized by using a convergent synthetic
      strategy. These dendrimers can be functionalized quantitatively with small
      organic and biological molecules that contain hydrazide and/or alkyne groups in
      which each functional moiety is completely specific for its complementary motif.
      This orthogonal functionalization strategy has the potential to be used to
      synthesize multifunctional dendrimers for a variety of applications, which range
      from targeted biological delivery vehicles to optical materials.

PMID- 17508381
TI  - Understanding adsorption and interactions of alkane isomer mixtures in
      isoreticular metal-organic frameworks.
AB  - Novel metal-organic frameworks (MOFs) may lead to advances in adsorption and
      catalysis owing to their superior properties compared to traditional nanoporous
      materials. A combination of the grand canonical Monte Carlo method and
      configurational-bias Monte Carlo simulation was used to evaluate the adsorption
      isotherms of C4-C6 alkane isomer mixtures in IRMOF-1 and IRMOF-6. The amounts of
      adsorbed linear and branched alkanes increase with increasing pressure, and the
      amount of branched alkanes is larger than that of the linear ones. The locations
      of the alkane isomer reveal that the Zn4O clusters of the IRMOFs are the
      preferential adsorption sites for the adsorbate molecules. The interaction energy
      between the Zn4O cluster and the adsorbate is larger than that between the
      organic linker and the adsorbate. It was further confirmed that the Zn4O cluster
      plays a much more important role in adsorption by pushing a probe molecule into
      the pore at positions closer to the Zn4O cluster. It is difficult for branched
      alkane molecules to approach the Zn4O cluster of IRMOF-6 closely owing to strong
      spatial hindrance. In addition, the adsorption selectivity is discussed from the
      viewpoints of thermodynamics and kinetics, and the diffusion behavior of n-butane
      and 2-methylpropane were investigated to illustrate the relationship between
      diffusion and adsorption.

PMID- 17508382
TI  - A sol-gel-modified poly(methyl methacrylate) electrophoresis microchip with a
      hydrophilic channel wall.
AB  - A sol-gel method was employed to fabricate a poly(methyl methacrylate) (PMMA)
      electrophoresis microchip that contains a hydrophilic channel wall. To fabricate
      such a device, tetraethoxysilane (TEOS) was injected into the PMMA channel and
      was allowed to diffuse into the surface layer for 24 h. After removing the excess
      TEOS, the channel was filled with an acidic solution for 3 h. Subsequently, the
      channel was flushed with water and was pretreated in an oven to obtain a sol-gel
      modified PMMA microchip. The water contact angle for the sol-gel-modified PMMA
      was approximately 27.4 degrees compared with approximately 66.3 degrees for the
      pure PMMA. In addition, the electro-osmotic flow increased from 2.13x10(-4) cm2
      V(-1) s(-1) for the native-PMMA channel to 4.86x10(-4) cm2 V(-1) s(-1) for the
      modified one. The analytical performance of the sol-gel-modified PMMA microchip
      was demonstrated for the electrophoretic separation of several purines, coupled
      with amperometric detection. The separation efficiency of uric acid increased to
      74,882.3 m(-1) compared with 14,730.5 m(-1) for native-PMMA microchips. The
      result of this simple modification is a significant improvement in the
      performance of PMMA for microchip electrophoresis and microfluidic applications.

PMID- 17508383
TI  - On the mechanism and stereochemistry of chiral lithium-carbenoid-promoted
      cyclopropanation reactions.
AB  - An investigation into the mechanism and stereochemistry of chiral lithium
      carbenoid-promoted cyclopropanation reactions by using density functional theory
      (DFT) methods is reported. Previous work suggested that this type of
      cyclopropanation reaction may proceed by competition between a methylene-transfer
      mechanism and a carbometalation mechanism. In this paper, it is demonstrated that
      the intramolecular cyclopropanation reactions promoted by chiral carbenoids 1 and
      2 proceed by the methylene-transfer mechanism. The carbometalation mechanism was
      found to have a much higher reaction barrier and does not appear to compete with
      the methylene-transfer mechanism. The Lewis base group does not enhance the
      carbometalation pathway enough to compete with the methylene-transfer pathway.
      The present computational results are consistent with experimental observations
      for these cyclopropanation reactions. The factors governing the stereochemistry
      of the intramolecular cyclopropanation reaction by the methylene-transfer
      mechanism were examined to help elucidate the origin of the stereoselectivity
      observed in experiments. Both the directing group and the configuration at the
      C(1) centre were found to play a key role in the stereochemistry. Carbenoid 1 has
      a chiral C(1) centre of R configuration. The Lewis base group directs the
      cyclization of carbenoid 1 to form a single product. In contrast, the Lewis base
      group cannot direct the cyclization of carbenoid 2 to furnish a stereoselective
      product due to the S configuration of the chiral C(1) centre in carbenoid 2. This
      relationship of the stereochemistry to the chiral character of the carbenoid has
      implications for the design of new efficient carbenoid reagents for
      stereoselective cyclopropanation.

PMID- 17508384
TI  - Remote radio-frequency controlled nanoliter chemistry and chemical delivery on
      substrates.

PMID- 17508385
TI  - A formally zwitterionic ruthenium catalyst precursor for the transfer
      hydrogenation of ketones that does not feature an ancillary ligand N-H
      functionality.

PMID- 17508386
TI  - Rhodium-catalyzed aryl transfer from trisubstituted aryl methanols to alpha,beta
      unsaturated carbonyl compounds.

PMID- 17508387
TI  - Interactions of microcrystals through free pyridyl groups: microcross and chain
      arrayed supercrystals of a palladium(II) complex.

PMID- 17508388
TI  - Imidazolyl cyclodextrins: artificial serine proteases enabling regiospecific
      reactions.

PMID- 17508389
TI  - Oral vaccines: new needs, new possibilities.
AB  - Vaccination is an important tool for handling healthcare programs both in
      developed and developing countries. The current global scenario calls for a more
      efficacious, acceptable, cost-effective and reliable method of immunization for
      many fatal diseases. It is hoped that the adoption of oral vaccines will help to
      provide an effective vaccination strategy, especially in developing countries.
      Mucosal immunity generated by oral vaccines can serve as a strong first line of
      defense against most of the pathogens infecting through the mucosal lining.
      Advances in elucidating the mechanism of action of oral vaccines will facilitate
      the design of more effective, new generation vaccines. There are promising
      developments in the use of different agents to effectively deliver the vaccine
      candidate. It is hoped that ongoing research may be able to set another cardinal
      point, after polio vaccine, in eradicating infectious diseases.

PMID- 17508390
TI  - How do synonymous mutations affect fitness?
AB  - While it has often been assumed that, in humans, synonymous mutations would have
      no effect on fitness, let alone cause disease, this position has been questioned
      over the last decade. There is now considerable evidence that such mutations can,
      for example, disrupt splicing and interfere with miRNA binding. Two recent
      publications suggest involvement of additional mechanisms: modification of
      protein abundance most probably mediated by alteration in mRNA stability and
      modification of protein structure and activity, probably mediated by induction of
      translational pausing. These case histories put a further nail into the coffin of
      the assumption that synonymous mutations must be neutral.

PMID- 17508391
TI  - Early mouse embryo development: could epigenetics influence cell fate
      determination?
AB  - It is generally assumed that the developmental program of embryogenesis relies on
      epigenetic mechanisms. However, a mechanistic link between epigenetic marks and
      cell fate decisions had not been established so far. In a recent article, Torres
      Padilla and colleagues show that epigenetic information and, more precisely,
      histone arginine methylation mediated by CARM1 could contribute to cell fate
      decisions in the mouse 4-cell-stage embryo. It provides the first indications
      that global epigenetic information influences allocation of pluripotent cells
      toward the first cell lineages.

PMID- 17508392
TI  - Dynamic mutations as digital genetic modulators of brain development, function
      and dysfunction.
AB  - A substantial portion of the human genome has been found to consist of simple
      sequence repeats, including microsatellites and minisatellites. Microsatellites,
      tandem repeats of 1-6 nucleotides, form the template for dynamic mutations, which
      involve heritable changes in the lengths of repeat sequences. In recent years, a
      large number of human disorders have been found to be caused by dynamic
      mutations, the most common of which are trinucleotide repeat expansion diseases.
      Dynamic mutations are common to numerous nervous system disorders, including
      Huntington's disease, various spinocerebellar ataxias, fragile X syndrome,
      fragile X tremor/ataxia syndrome, Friedreich ataxia and other neurodegenerative
      disorders. The involvement of dynamic mutations in brain disorders will be
      reviewed, with a focus on the large group caused by CAG/glutamine repeat
      expansions. We will also outline a proposed role of tandem repeat polymorphisms
      (TRPs), with unique 'digital' genetic distributions, in modulating brain
      development and normal function, so as to generate additional mutational
      diversity upon which natural selection may act.

PMID- 17508393
TI  - Expression of HSP72 after ELF-EMF exposure in three cell lines.
AB  - It has been reported that magnetic fields with flux densities ranging from microT
      to mT are able to induce heat shock factor, HSP72 mRNA or heat shock proteins in
      various cells. In this study we investigated changes in the HSP72 mRNA
      transcription level in three cell lines (HL-60, H9c2, and Girardi heart cells)
      and in the intracellular HSP72 protein content in two cell lines (HL-60 and
      Girardi heart cells) after treatment schemes using electromagnetic fields with a
      flux density of 2 microT to 4 mT, a frequency of 50 Hz and exposure times from 15
      to 30 min. None of the treatments or modalities showed any significant effect on
      the HSP72 protein level, although HSP72 mRNA could be induced, at least to some
      extent, with one of the parameter combinations in all cell lines tested.
      Obviously, HSP72 mRNA transcription and translation are not necessarily coupled
      in certain cells. This leads to the conclusion that electromagnetic field effects
      on HSP72 mRNA levels are not indicative for downstream effects unless increased
      mRNA levels can be correlated with increased HSP72 protein levels as well.

PMID- 17508394
TI  - Size and shape: the developmental regulation of static allometry in insects.
AB  - Among all organisms, the size of each body part or organ scales with overall body
      size, a phenomenon called allometry. The study of shape and form has attracted
      enormous interest from biologists, but the genetic, developmental and
      physiological mechanisms that control allometry and the proportional growth of
      parts have remained elusive. Recent progress in our understanding of body-size
      regulation provides a new synthetic framework for thinking about the mechanisms
      and the evolution of allometric scaling. In particular, insulin/IGF signaling,
      which plays major roles in longevity, diabetes and the regulation of cell, organ
      and body size, might also be centrally involved in regulating organismal shape.
      Here we review recent advances in the fields of growth regulation and
      endocrinology and use them to construct a developmental model of static allometry
      expression in insects. This model serves as the foundation for a research program
      that will result in a deeper understanding of the relationship between growth and
      form, a question that has fascinated biologists for centuries.

PMID- 17508395
TI  - Rebuilding microbial genomes.
AB  - Engineered microbes are of great potential utility in biotechnology and basic
      research. In principle, a cell can be built from scratch by assembling small
      molecule sets with auto-catalytic properties. Alternatively, DNA can be isolated
      or directly synthesized and molded into a synthetic genome using existing genomic
      blueprints and molecular biology tools. Activating such a synthetic genome will
      yield a synthetic cell. Here we examine obstacles associated with this latter
      approach using a model system whereby a donor genome from H. influenzae is
      fragmented, and the pieces are then modified and reassembled stepwise in an E.
      coli host cell. There are obstacles associated with this strategy related to DNA
      transfer, DNA replication, cross-talk in gene regulation and compatibility of
      gene products between donor and host. Encouragingly, analysis of gene expression
      indicates widespread transcription of H. influenzae genes in E. coli, and
      analysis of gap locations in H. influenzae and other microbial genome assemblies
      reveals few genes routinely incompatible with E. coli. In conclusion, rebuilding
      and booting a genome remains a feasible and pragmatic approach to creating a
      synthetic microbial cell.

PMID- 17508396
TI  - Facile synthetic route to enantiopure unsymmetric cis-2,5-disubstituted
      pyrrolidines.
AB  - The (+/-)-cis-5-arylcarbamoyl-2-ethoxycarbonylpyrrolidines 6a-g were firstly
      synthesized in 53-64% yields by using meso-diethyl-2,5-dibromoadipate 3 and (S)-(
      )-1-phenylethylamine in three steps. The diastereomeric mixture (S;2S,5R)-(-)-7
      and (S;2R,5S)-(+)-8 were prepared by the Grignard reaction and separated by a
      flash column chromatography in 29 and 52% yields. The absolute configurations of
      (+)-8 was confirmed by X-ray crystallographic analysis and the enantiopure
      pyrrolidines (2S,5R)-(-)-9/(2R,5S)-(+)-9 and (2S,5R)-(-)-10/(2R,5S)-(+)-10 were
      obtained in good yields.

PMID- 17508397
TI  - Pyramidal inversion mechanism of simple chiral and achiral sulfoxides: a
      theoretical study.
AB  - The pyramidal inversion mechanism of simple sulfoxides was studied, employing ab
      initio and DFT methods. The convergence of the geometrical and energetic
      parameters of H2SO and DMSO with respect to the Hamiltonian and basis set was
      analyzed in order to determine a computational level suitable for methyl phenyl
      sulfoxide (3), methyl 4-cyanophenyl sulfoxide (4), diphenyl sulfoxide (5), 4,4'
      dicyanodiphenyl sulfoxide (6), benzyl methyl sulfoxide (7) and benzyl phenyl
      sulfoxide (8). The DFT B3LYP/6-311G(d,p) level was chosen for further
      calculations of larger sulfoxides. The barriers DeltaE calculated for the
      pyramidal inversion mechanism of sulfoxides 3-8 are in the range of 38.7-47.1
      kcal/mol. These values are in good agreement with the experimental barriers for
      racemization via the pyramidal inversion mechanism. A resonance effect of a
      phenyl ring selectively stabilizes the transition state conformations, decreasing
      the energy barrier for pyramidal inversion by about 3 kcal/mol, compared to a
      similar molecule without a phenyl substituent. Introducing electron withdrawing
      groups (cyano) at the para positions of the phenyl ring(s) causes a further
      decrease of the energy barrier.

PMID- 17508398
TI  - Enantioselective and diastereoselective separation of synthetic pyrethroid
      insecticides on a novel chiral stationary phase by high-performance liquid
      chromatography.
AB  - A novel chiral packing material for high-performance liquid chromatography (HPLC)
      was prepared by connecting (R)-1-phenyl-2-(4-methylphenyl) ethylamine (PTE) amide
      derivative of (S)-isoleucine to aminopropyl silica gel through 2-amino-3,5
      dinitro-1-carboxamido-benzene unit. This chiral stationary phase was applied to
      the enantioselective and diastereoselective separation of five pyrethroid
      insecticides by HPLC under normal phase condition. To achieve satisfactory
      baseline separation an optimization of the variables of mobile phase composition
      was required. The two enantiomers of fenpropathrin and four stereoisomers of
      fenvalerate were baseline separated using hexane-1,2-dichloroethane-2-propanol as
      mobile phase. The results show that the enantioselectivity of CSP is better than
      Pirkle type 1-A column for these compounds. Only partial separations for the
      cypermethrin and cyfluthrin stereoisomers were observed. Seven peaks and eight
      peaks were observed for cypermethrin and cyfluthrin, respectively. The elution
      orders were assigned by using different stereoisomer-enriched products.

PMID- 17508400
TI  - Chiroptical properties of diamino carboxylic acids.
AB  - Diamino carboxylic acids have recently come to the attention of scientists
      working in the field of early life and its development. These are the monomers of
      a hypothetic early form of genetic material, the so-called Peptide Nucleic Acid
      (PNA) (Nielson et al., Proc Natl Acad Sci USA 2000;97:3868-3871). Since all
      biopolymers rely on a specific handedness of their building blocks, the question
      of symmetry breaking occurs in diamino acids and PNA in the same way as in amino
      acids and proteins. One possible mechanism for triggering this, is asymmetric
      photochemistry in interstellar/circumstellar matter by means of circularly
      polarized light (Bailey et al., Science 2005;281:672-674; Bailey, Orig Life Evol
      Biosphere 2001;21:167-183; Buschermohle, Astrophys J 2005;624:821-826;
      Meierhenrich, Angew Chem Int Ed Engl 2005;44:5630-5634). Here we have measured
      the CD-spectra of four chiral diamino carboxylic acids, three of which were found
      in the Murchison meteorite (Meierhenrich, Proc Natl Acad Sci USA 2004;101:9182
      9186). The spectra show a uniform peak at 200 nm. These results and additional
      quantum mechanical calculations of the involved molecular orbitals support the
      assumption that the process of symmetry breaking in diamino acids does not depend
      significantly on the length of the side chain. This means that one process alone
      could suffice to lead to symmetry breaking in all four measured diamino
      carboxylic acids and might even to some extent be transferable to monoamino
      acids, the monomers of proteins.

PMID- 17508399
TI  - The diverse functions of Kruppel-like factors 4 and 5 in epithelial biology and
      pathobiology.
AB  - The Kruppel-like factors (KLFs) comprise a family of evolutionarily conserved
      zinc finger transcription factors that regulate numerous biological processes
      including proliferation, differentiation, development and apoptosis. KLF4 and
      KLF5 are two closely related members of this family and are both highly expressed
      in epithelial tissues. In the intestinal epithelium, KLF4 is expressed in
      terminally differentiated epithelial cells at the villus borders of the mucosa
      and inhibits cell growth, while KLF5 is expressed in proliferating epithelial
      cells at the base of the intestinal crypts and promotes cell growth. KLF4 and
      KLF5 respond to a myriad of external stress stimuli and are likely involved in
      restoring cellular homeostasis following exposure to stressors. Confirming their
      importance in maintaining tissue integrity, KLF4 and KLF5 are both dysregulated
      in various types of cancer. Here we review the recent advances in defining the
      physiological and pathobiological roles of KLF4 and KLF5, focusing on their
      functions in the intestinal epithelium.

PMID- 17508402
TI  - Evolution of direct-developing larvae: selection vs loss.
AB  - Observations of a sea urchin larvae show that most species adopt one of two life
      history strategies. One strategy is to make numerous small eggs, which develop
      into a larva with a required feeding period in the water column before
      metamorphosis. In contrast, the second strategy is to make fewer large eggs with
      a larva that does not feed, which reduces the time to metamorphosis and thus the
      time spent in the water column. The larvae associated with each strategy have
      distinct morphologies and developmental processes that reflect their feeding
      requirements, so that those that feed exhibit indirect development with a complex
      larva, and those that do not feed form a morphologically simplified larva and
      exhibit direct development. Phylogenetic studies show that, in sea urchins, a
      feeding larva, the pluteus, is the ancestral form and the morphologically
      simplified direct-developing larva is derived. The current hypothesis for
      evolution of the direct-developing larval form in sea urchins suggests that major
      developmental changes occur by neutral loss of larval features after the crucial
      transition to a nonfeeding life history strategy. We present evidence from
      Clypeaster rosaceus, a sea urchin with a life history intermediate to the two
      strategies, which indicates that major developmental changes for accelerated
      development have been selected for in a larva that can still feed and maintains
      an outward, pluteus morphology. We suggest that transformation of larval form has
      resulted from strong selection on early initiation and acceleration of adult
      development.

PMID- 17508401
TI  - Mutational activation of ErbB family receptor tyrosine kinases: insights into
      mechanisms of signal transduction and tumorigenesis.
AB  - Signaling by the Epidermal Growth Factor Receptor (EGFR) and related ErbB family
      receptor tyrosine kinases can be deregulated in human malignancies as the result
      of mutations in the genes that encode these receptors. The recent identification
      of EGFR mutations that correlate with sensitivity and resistance to EGFR tyrosine
      kinase inhibitors in lung and colon tumors has renewed interest in such
      activating mutations. Here we review current models for ligand stimulation of
      receptor dimerization and for activation of receptor signaling by receptor
      dimerization. In the context of these models, we discuss ErbB receptor mutations
      that affect ligand binding and those that cause constitutive receptor
      phosphorylation and signaling as a result of constitutive receptor dimerization.
      We discuss mutations in the cytoplasmic regions that affect enzymatic activity,
      substrate specificity and coupling to effectors and downstream signaling
      pathways. Finally, we discuss how emergent mechanisms of ErbB receptor mutational
      activation could impact the search for clinically relevant ErbB receptor
      mutations.

PMID- 17508403
TI  - Cardiomyocytes from human embryonic stem cells: more than heart repair alone.
AB  - One of the most-exciting and controversial discoveries of the last decade has
      been the isolation of embryonic stem cells from human embryos. The capacity of
      these cells to form all somatic cell types in the human body has captured the
      imagination of researcher and clinician alike, the perspectives that they
      represent for cell replacement therapies in multiple chronic disorders being used
      to justify the use of embryos for this purpose. However, there is a gradual
      realization that cell therapies are in the far future and some find that the
      other, more immediately applicable, types of research give less justification for
      the use of embryos. Here, cardiomyocytes derived from human embryonic stem cells
      are discussed. The research opportunities created by having human heart cells
      available routinely in the laboratory are explored and the types of questions
      that can be addressed are placed in the context of alternative cell and animal
      models.

PMID- 17508404
TI  - In the beginning: the initiation of meiosis.
AB  - The most-critical point of reproductive development in all sexually reproducing
      species is the transition from mitotic to meiotic cell cycle. Studies in
      unicellular fungi have indicated that the decision to enter meiosis must be made
      before the beginning of the premeiotic S phase. Recent data from the mouse
      suggest that this timing of meiosis initiation is a universal feature shared also
      by multicellular eukaryotes. In contrast, the signaling cascade that leads to
      meiosis initiation shows great diversity among species.

PMID- 17508405
TI  - Ornithine decarboxylase activity of L929 cells after exposure to continuous wave
      or 50 Hz modulated radiofrequency radiation--a replication study.
AB  - A replication study with some extensions was made to confirm enhancement of
      ornithine decarboxylase (ODC) activity in murine L929 fibroblasts after
      radiofrequency (RF) field exposure reported in earlier studies. L929 cells
      purchased from two cell banks were exposed for 2, 8, or 24 h to continuous wave
      or DAMPS (burst modulated at 50 Hz, with 33% duty cycle) signals at specific
      absorption rate (SAR) levels of 2.5 or 6.0 W/kg. Exposures were carried out in
      Crawford and waveguide chambers, at frequencies 835 and 872 MHz, respectively.
      The results did not confirm findings of previous studies reporting increased ODC
      activity in RF-exposed cells. When Crawford cell exposure system was used, ODC
      activity was either not affected (in the case of 8 or 24 h exposures) or
      decreased after 2 h exposure at the highest SAR level (6 W/kg). The decrease was
      most pronounced when cooling with air flow was not used, and is most likely
      related to increased temperature. The minor methodological differences (use of
      antibiotics, increased sensitivity of ODC assay) are not likely to explain the
      inconsistency of the findings of the present and previous studies. Different
      results were obtained in experiments with the waveguide system that involves more
      efficient temperature control. In this exposure system, ODC activity was
      increased after 8 h exposure at 6 W/kg. Further studies are warranted to explore
      whether this finding reflects a true non-thermal effect. The present study did
      not provide evidence for modulation-specific effects reported in earlier studies.

PMID- 17508406
TI  - Response to Dagan and Martin.

PMID- 17508407
TI  - Comments of Poole and Penny's essay "Evaluating hypotheses for the origin of
      eukaryotes", BioEssays 29:74-84.

PMID- 17508408
TI  - Repetitive short-course hepatic arterial infusion chemotherapy with high-dose 5
      fluorouracil and cisplatin in patients with advanced hepatocellular carcinoma.
AB  - BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has often been selected
      as a therapeutic option for patients with advanced hepatocellular carcinoma
      (HCC). The objective of the current study was to evaluate the efficacy and safety
      of repetitive HAIC with high-dose 5-fluorouracil (5-FU) and cisplatin given for 3
      days in patients with advanced HCC. METHODS: Between January 2001 and December
      2004, a total of 41 patients with unresectable advanced HCC were enrolled. The
      patients underwent HAIC via the implantable port system with 5-FU (at a dose of
      500 mg/m(2) on Days 1-3) and cisplatin (at a dose of 60 mg/m(2) on Day 2) every 4
      weeks. Tumor response was assessed at the end of every 3 cycles. RESULTS: The
      median age of the patients was 53 years and 34 patients (82.9%) had evidence of
      portal vein thrombosis. In total, 230 cycles of HAIC were administered to the 41
      patients, with a median of 6 cycles given (range, 1-14 cycles). Nine patients
      (22.0%) achieved a partial response and 14 patients (34.1%) had stable disease.
      The median time to disease progression and overall survival were 7.0 months and
      12.0 months, respectively. The overall survival was found to be significantly
      longer in the successful disease control group (patients with a complete
      response, partial response, and stable disease) than in the disease progression
      group (median of 14.0 months vs 6.0 months; P < .001). Adverse reactions were
      tolerable and successfully managed with conservative treatment. CONCLUSIONS: HAIC
      with high-dose 5-FU and cisplatin given for 3 days achieved effective and safe
      results in patients with advanced HCC. Therefore, repetitive short-course HAIC
      with high-dose 5-FU and cisplatin may be useful as an alternative therapeutic
      option for patients with advanced HCC.

PMID- 17508409
TI  - Reduced XPC messenger RNA level may predict a poor outcome of patients with
      nonsmall cell lung cancer.
AB  - BACKGROUND: Homologous deletion of the xeroderma pigmentosum complementary group
      C (XPC) repair gene frequently causes lung adenocarcinoma in mice, suggesting
      that an XPC defect may play a critical role in lung tumorigenesis. The current
      study attempted to determine whether reduced XPC mRNA levels predict the clinical
      outcome of lung cancer patients. METHODS: XPC, p27(kip) (cdk inhibitory protein),
      and S-phase kinase-associated protein (skp2) levels were evaluated by Western
      blot analysis in a series of lung cancer cell lines with different invasive
      abilities. Migration and invasive abilities were measured using a modified Boyden
      chamber without and with Matrigel, respectively. To test whether XPC affects cell
      invasive ability, XPC gene protein expression was reduced in low invasive cells
      by RNA interference (RNAi) and assayed with Boyden chamber. XPC mRNA levels in
      126 nonsmall cell lung cancers (NSCLCs) were examined by real-time-reverse
      transcriptase polymerase chain reaction (RT-PCR). The prognostic value of XPC
      mRNA expression was statistically analyzed by the Kaplan-Meier method and Cox
      proportional hazards regression. RESULTS: The expression of XPC was reduced with
      increasing invasive potential in CL1-series lung cancer cell lines. When the XPC
      level was reduced by RNAi, cell migration and invasiveness increased markedly;
      the increased invasiveness may be caused by decreased expression of p27(kip) and
      increased expression of skp2 and E2F transcription factor 1. To determine whether
      reduced XPC expression was correlated with tumor aggressiveness and poor patient
      survival, XPC mRNA levels were evaluated by real-time RT-PCR. Kaplan-Meier
      analysis demonstrated that the median survival of patients with lower XPC mRNA
      levels was shorter compared with patients with higher XPC mRNA levels (P =
      .0440). Cox regression analysis further indicated that XPC mRNA level may act as
      an independent prognostic factor for NSCLC patients (P = .014). CONCLUSIONS: The
      results of the current study suggest that reduced XPC mRNA level may constitute
      an independent prognostic factor for NSCLC patients.

PMID- 17508411
TI  - Highly accurate biomolecular electrostatics in continuum dielectric environments.
AB  - Implicit solvent models based on the Poisson-Boltzmann (PB) equation are
      frequently used to describe the interactions of a biomolecule with its dielectric
      continuum environment. A novel, highly accurate Poisson-Boltzmann solver is
      developed based on the matched interface and boundary (MIB) method, which
      rigorously enforces the continuity conditions of both the electrostatic potential
      and its flux at the molecular surface. The MIB based PB solver attains much
      better convergence rates as a function of mesh size compared to conventional
      finite difference and finite element based PB solvers. Consequently, highly
      accurate electrostatic potentials and solvation energies are obtained at coarse
      mesh sizes. In the context of biomolecular electrostatic calculations it is
      demonstrated that the MIB method generates substantially more accurate solutions
      of the PB equation than other established methods, thus providing a new level of
      reference values for such models. Initial results also indicate that the MIB
      method can significantly improve the quality of electrostatic surface potentials
      of biomolecules that are frequently used in the study of biomolecular
      interactions based on experimental structures.

PMID- 17508410
TI  - Reaction of hypochlorous acid with imidazole: formation of 2-chloro- and 2
      oxoimidazoles.
AB  - Reaction of hypochlorous acid (HOCl) with imidazole (Im) taken as a model for the
      5-membered ring of guanine, leading to the products 2-chloro- and 2-oxo
      imidazoles was investigated at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels of
      density functional theory. For all cases, single point energy calculations were
      performed at the MP2/AUG-cc-pVDZ level of theory using the geometries optimised
      at the B3LYP/AUG-cc-pVDZ level. Intrinsic reaction coordinate calculations were
      performed to ensure genuineness of all the calculated transition states. Effect
      of aqueous media was investigated by solvating all the species involved in the
      reactions using the polarizable continuum model. It is found that 2
      chloroimidazole (2-ClIm) can be formed following three different reaction schemes
      while 2-oxoimidazole (2-oxoIm) can be formed following two different reaction
      schemes. The calculated barrier energies show that formation of 2-oxoIm would be
      less favored than that of 2-ClIm, which explains the experimental observations on
      relative yields of 8-chlorodeoxyguanosine and 8-oxodeoxyguanosine.

PMID- 17508412
TI  - Visualization and integration of quantum topological atoms by spatial
      discretization into finite elements.
AB  - We present a novel algorithm to integrate property densities over the volume of a
      quantum topological atom. Atoms are grown outward, starting from a sphere
      centered on the nucleus, by means of a finite element meshing algorithm. Bond
      critical points and ring critical points require special treatment. The overall
      philosophy as well as intricate features of this meshing algorithm are given,
      followed by details of the quadrature over the finite elements. An effort has
      been made to design a streamlined and compact algorithm, focusing on the core of
      challenges arising in tracing the electron density's gradient vector field. The
      current algorithm also generates a new type of pictures that can be a Graphical
      User Interface. Excellent integration errors, L(Omega), are obtained, even for
      atoms with (narrow) tails or sharp corners.

PMID- 17508413
TI  - Relativistic correlating basis sets for actinide atoms from 90Th to 103Lr.
AB  - For 14 actinide atoms from (90)Th to (103)Lr, contracted Gaussian-type function
      sets are developed for the description of correlations of the 5f, 6d, and 7s
      electrons. Basis sets for the 6d orbitals are also prepared, since the orbitals
      are important in molecular environments despite their vacancy in the ground state
      of some actinides. A segmented contraction scheme is employed for the compactness
      and efficiency. Contraction coefficients and exponents are so determined as to
      minimize the deviation from accurate natural orbitals of the lowest term arising
      from the 5f(n-1)6d(1)7s(2) configuration. The spin-free relativistic effects are
      considered through the third-order Douglas-Kroll approximation. To test the
      present correlating sets, all-electron calculations are performed on the ground
      state of (90)ThO molecule. The calculated spectroscopic constants are in
      excellent agreement with experimental values.

PMID- 17508414
TI  - Soft tissue reactions to bioactive glass 13-93 combined with chitosan.
AB  - The aim of this study was to evaluate rabbit soft tissue reactions to bioactive
      glass 13-93 mesh by using a histological and immunohistochemical analysis.
      Bioactive glass (13-93) mesh fixed with 3 wt % chitosan was implanted into the
      dorsal subcutaneous space of New Zealand White rabbits (n=18) for six, 12, and 24
      weeks, respectively. After 6 weeks the bioactive glass remnants were surrounded
      by foreign-body granuloma with eosinophilic granulocytes. After 12 and 24 weeks
      the implanted material was mainly absorbed, but, if any particles still remained
      the foreign-body reaction was notably milder. Yet, a mild chronic inflammatory
      infiltrate was present. Matrix metalloproteinase (MMP) -2, -3, -13 and tissue
      inhibitory protein (TIMP-1 and -2) expressions were studied by
      immunohistochemistry. MMP-3, -13, TIMP-1, and -2 positivity were detected
      throughout the follow-up period. MMP-2 positivity was only occasionally seen in
      the 24 week samples, which is constitutively expressed but is not related to
      inductive MMP-3 and -13 cascade. The presence of eosinophilic granulocytes in
      some of the samples raises the possibility of an allergic reaction to the
      materials. MMP-3 and -13 are suggested to participate in the host reaction to
      either bioactive glass or chitosan.

PMID- 17508415
TI  - Fracture modes under uniaxial compression in hydroxyapatite scaffolds fabricated
      by robocasting.
AB  - The fracture modes of hydroxyapatite (HA) scaffolds fabricated by direct-write
      assembly (robocasting) are analyzed in this work. Concentrated HA inks with
      suitable viscoelastic properties were developed to enable the fabrication of
      prototype structures consisting of a 3-D square mesh of interpenetrating rods.
      The fracture behavior of these model scaffolds under compressive stresses is
      determined from in situ uniaxial tests performed in two different directions:
      perpendicular to the rods and along one of the rod directions. The results are
      analyzed in terms of the stress field calculated by finite element modeling
      (FEM). This analysis provides valuable insight into the mechanical behavior of
      scaffolds for bone tissue engineering applications fabricated by robocasting.

PMID- 17508416
TI  - Aligned electrospun nanofibers specify the direction of dorsal root ganglia
      neurite growth.
AB  - Nerve injury, a significant cause of disability, may be treated more effectively
      using nerve guidance channels containing longitudinally aligned fibers. Aligned,
      electrospun nanofibers direct the neurite growth of immortalized neural stem
      cells, demonstrating potential for directing regenerating neurites. However, no
      study of neurite guidance on these fibers has yet been performed with primary
      neurons. Here, we examined neurites from dorsal root ganglia explants on
      electrospun poly-L-lactate nanofibers of high, intermediate, and random
      alignment. On aligned fibers, neurites grew radially outward from the ganglia and
      turned to follow the fibers upon contact. Neurite guidance was robust, with
      neurites never leaving the fibers to grow on the surrounding cover slip. To
      compare the alignment of neurites to that of the nanofiber substrates, Fourier
      methods were used to quantify the alignment. Neurite alignment, however striking,
      was inferior to fiber alignment on all but the randomly aligned fibers. Neurites
      on highly aligned substrates were 20 and 16% longer than neurites on random and
      intermediate fibers, respectively. Schwann cells on fibers assumed a very narrow
      morphology compared to those on the surrounding coverslip. The robust neurite
      guidance demonstrated here is a significant step toward the use of aligned,
      electrospun nanofibers for nerve regeneration. (c) 2007 Wiley Periodicals, Inc. J
      Biomed Mater Res, 2007.

PMID- 17508417
TI  - Successful treatment with infliximab of refractory pyoderma gangrenosum in 2
      patients with inflammatory bowel diseases.

PMID- 17508418
TI  - Assessment of endoscopic activity index and biological inflammatory markers in
      clinically active Crohn's disease with normal C-reactive protein serum level.
AB  - BACKGROUND: Patients with clinically active Crohn's disease (CD), defined by a
      Crohn's Disease Activity Index (CDAI)>150, may have normal C-reactive protein
      (CRP) serum levels. In such cases, it is difficult to know whether these patients
      have really active disease or rather functional symptoms. This distinction is
      important to decide the most appropriate treatment. The aim of our work was to
      assess intestinal and colonic lesions in such patients and to look for biological
      markers potentially associated with endoscopic activity of the disease. METHODS:
      We included 28 consecutive CD patients with CDAI>150 and a normal CRP level.
      These patients underwent a full colonoscopy with Crohn's Disease Endoscopy Index
      of Severity (CDEIS) calculation, fecal calprotectin, blood fibrinogen, acid alpha
      1 glycoprotein, and erythrocyte sedimentation rate measurement. The Harvey
      Bradshaw score was also calculated. Serum IL1 beta, IL6, IL8, sIL2R, and sTNFR2
      were measured. RESULTS: The median CDAI was 181 (151-485). Almost all (92.9%)
      these patients had endoscopic lesions, but the majority had only mild lesions
      (CDEIS<or=6). No correlation was found between CDEIS and any of the clinical or
      biological markers. However, all the patients with significant endoscopic lesions
      (defined by a CDEIS>6) had previous surgical intestinal resection and lesions
      involving the anastomosis. CONCLUSIONS: Patients with elevated CDAI and normal
      CRP have only mild mucosal lesions of CD. Most significant lesions may be
      observed at the anastomosis and proximal to it in previously operated patients.
      None of the biological markers tested was associated with these endoscopic
      lesions.

PMID- 17508419
TI  - Determinants of male sexual function in inflammatory bowel disease: a survey
      based cross-sectional analysis in 280 men.
AB  - BACKGROUND: Problems with intimacy and sexual performance are among the major
      concerns of patients with inflammatory bowel disease (IBD). This study was
      performed to identify disease-related factors associated with low sexual function
      in men. METHODS: Consecutive patients were surveyed using a standardized
      questionnaire. A random sample from the national patients' organization was also
      included. Low sexual function was defined as a score < -1 on a z-normalized scale
      of the International Index of Erectile Function. Results are presented as
      adjusted odds ratios (ORs) with 95% confidence interval (CI) based on multiple
      logistic regression. RESULTS: 280 questionnaires were available for analysis.
      Scores were similar between the groups and compared with general population
      means, with the exception of sexual desire. Of the clinical group, 44% felt
      severely compromised sexually due to their IBD. Erectile function was
      particularly sensitive to somatic problems (disease activity, OR 2.5, 95% CI: 1.3
      4.9; diabetes, OR 7.0, 95% CI: 1.4-35.0). The influence of depressive mood was
      restricted to aspects of satisfaction (sexual satisfaction, OR 2.3, 95% CI 1.1
      4.9; overall satisfaction OR 3.7, 95% CI: 1.7-8.3). CONCLUSIONS: Sexual function
      was relatively better with longer disease duration and was not affected by the
      long-term severity of the disease.

PMID- 17508420
TI  - Contribution of the novel inflammatory bowel disease gene IL23R to disease
      susceptibility and phenotype.
AB  - BACKGROUND: A North American genome-wide single nucleotide polymorphism (SNP)
      association study identified IL23R as a novel inflammatory bowel disease (IBD)
      susceptibility gene. Association was reported with multiple risk variants in the
      centromeric portion of IL23R in 3 large independent cohorts. The aims of this
      study were to replicate the association of IL23R with Crohn's disease (CD),
      examine subphenotype relationships, and look for evidence of epistasis with the
      known CD susceptibility gene CARD15 and susceptibility haplotype IBD5 in a large
      collection of CD patients. We further investigated the relationship between IL23R
      and ulcerative colitis (UC). METHODS: In all, 604 CD and 647 UC patients who had
      been rigorously phenotyped and who had been recruited from a single UK center
      were used in this study. Controls were either spouses of patients (141) or were
      recruited from well-person clinics (993). Eight SNPs were genotyped using
      MassArray (Sequenom). All 8 SNPs genotyped were significantly associated with CD.
      RESULTS: The association with the nonsynonymous SNP rs11209026 was confirmed
      (P=6.65x10(-6), odds ratio [OR], 0.43, 95% confidence interval [CI]: 0.29-0.64).
      The most significant SNP in our study was rs7517847 (P=4.9x10(-9), OR 0.65, 0.56
      0.75), which is statistically independent of rs11209026. Preliminary evidence
      suggests an epistatic interaction with the IBD5 risk haplotype. The effects of
      mutations in this IL23R appear weaker in UC (P=0.008, OR 0.63, 0.45-0.89 and
      0.005 OR, 0.81, 0.71-0.94, respectively). No subphenotype associations were
      identified. CONCLUSIONS: We confirmed the findings that IL23R is a susceptibility
      gene for IBD with suggestive epistasis with the IBD5 locus in the CD population.

PMID- 17508422
TI  - Capsule endoscopy in Crohn's disease: is seeing believing?

PMID- 17508423
TI  - Cancer-associated missplicing of exon 4 influences the subnuclear distribution of
      the DNA replication factor CIZ1.
AB  - Cip1-interacting zinc finger protein 1 (CIZ1, also known as CDKN1A-interacting
      zinc finger protein 1) stimulates initiation of mammalian DNA replication and is
      normally tethered to the nuclear matrix within DNA replication foci. Here, we
      show that an alternatively spliced human CIZ1 variant, lacking exon 4 (Delta E4),
      is misexpressed as a consequence of intronic mutation in Ewing tumor (ET) cell
      lines. In all ET lines tested, exon 4 is skipped and an upstream mononucleotide
      repeat element is expanded to contain up to 28 thymidines, compared to 16 in
      controls. In exon-trap experiments, a 24T variant produced three-fold more exon
      skipping than a 16T variant, demonstrating a direct effect on splicing. In
      functional assays, Delta E4 protein retains replication activity, but fails to
      form subnuclear foci. Furthermore, coexpression of mouse Delta E4 with Ciz1
      prevents Ciz1 from localizing appropriately, having a dominant negative effect on
      foci formation. The data show that conditional exclusion of exon 4 influences the
      spatial distribution of the Ciz1 protein within the nucleus, and raise the
      possibility that CIZ1 alternative splicing could influence organized patterns of
      DNA replication.

PMID- 17508424
TI  - Synergistic induction of cyclin D1 in oligodendrocyte progenitor cells by IGF-I
      and FGF-2 requires differential stimulation of multiple signaling pathways.
AB  - D-type cyclins are direct targets of extracellular signals and critical
      regulators of G(1) progression. Our previous data demonstrated that IGF-I and FGF
      2 synergize to enhance cyclin D1 expression, cyclin E/cdk2 complex activation,
      and S-phase entry in OP cells. Here, we provide a mechanistic explanation for how
      two growth factor signaling pathways converge on a major cell cycle regulator.
      IGF-I and FGF-2 differentially activate signaling pathways to coordinately
      promote cyclin D1 expression. We show that the p44/p42 MAPK signaling pathway is
      essential for FGF-2 induction of cyclin D1 mRNA. In contrast, blocking the PI3
      Kinase pathway results in loss of IGF-I/FGF-2 synergistic induction of cyclin D1
      protein levels. Moreover, the presence of IGF-I significantly enhances nuclear
      localization of cyclin D1, which also requires PI3K signaling. GSK-3beta, a
      downstream target of the PI3K/Akt pathway, is phosphorylated in the presence of
      IGF-I in OPs. Consistent with a known role for GSK-3beta in cyclin D1
      degradation, we show that proteasome inhibition in OPs exposed to FGF-2 increased
      cyclin D1 levels, equivalent to levels seen in IGF-I/FGF-2 treated cells. Thus,
      we provide a model for cyclin D1 coordinate regulation where FGF-2 stimulation of
      the MAPK pathway promotes cyclin D1 mRNA expression while IGF-I activation of the
      PI3K pathway inhibits proteasome degradation of cyclin D1 and enhances nuclear
      localization of cyclin D1.

PMID- 17508425
TI  - Cornelia de Lange syndrome: clinical review, diagnostic and scoring systems, and
      anticipatory guidance.
AB  - Cornelia de Lange syndrome (CdLS), also known as Brachmann-de Lange syndrome, is
      a well-described multiple malformation syndrome typically involving proportionate
      small stature, developmental delay, specific facial features, major malformations
      (particularly the cardiac, gastrointestinal and musculoskeletal systems), and
      behavioral abnormalities. There is a broad spectrum of clinical involvement, with
      increasing recognition of a much milder phenotype than previously recognized.
      Significant progress has been made in recent years in the clinical and molecular
      delineation of CdLS, necessitating a revision of the diagnostic criteria, more
      inclusive of the milder cases. In addition, a scoring system of severity has been
      found to correlate with specific brain changes. Thus, a clinical overview and
      recommendations for anticipatory guidance are timely in aiding caretakers and
      professionals to individualize care decisions and maximize developmental
      potential for individuals with CdLS. These guidelines are derived from consensus
      based on collective experience of over 500 patients with CdLS, observations of
      the natural history in children, adolescents, and adults, a review of the
      literature, and contacts with national support organizations in North America and
      Europe.

PMID- 17508426
TI  - Lack of association between Rh status, Rh immune globulin in pregnancy and
      autism.
AB  - Though causes of autism are considered largely genetic, considerable concern
      remains that exposure to Rh immune globulin (RhIg), which until 2001 in the
      United States contained the preservative thimerosal, can cause autism. To
      determine whether mothers of children with autism are more likely to be Rh
      negative (Rh(-)) or to have received RhIg preserved with thimerosal, which is
      49.6% ethyl mercury, we surveyed families of children with an autism spectrum
      disorder (ASD) ascertained through a University-based autism clinic considered
      free of ascertainment biases related to type of autism or severity. Between 2004
      and 2006, 305 mothers of 321 children with an ASD agreed to participate in a
      telephone interview. Analysis of complete records including the blood group
      status and RhIg exposure of 214 families showed that Rh(-) status is no higher in
      mothers of children with autism than in the general population, exposure to
      antepartum RhIg, preserved with thimerosal is no higher for children with autism
      and pregnancies are no more likely to be Rh incompatible. This was also true for
      autism subgroups defined by behavioral phenotype, gender, IQ, regressive onset,
      head circumference, dysmorphology, birth status, essential, or complex phenotype.
      These findings support the consensus that exposure to ethylmercury in thimerosal
      is not the cause of the increased prevalence of autism. These data are important
      not only for parents in this country but also for the international health
      community where thimerosal continues to be used to preserve multi-dose vials
      which in turn makes vaccines affordable.

PMID- 17508428
TI  - Current awareness in human psychopharmacology.

PMID- 17508429
TI  - Current world literature. Nephrology.

PMID- 17508430
TI  - Current world literature. Therapeutics and toxicology.

PMID- 17508431
TI  - Analysis supports most ambitious congressional health bills.

PMID- 17508433
TI  - Dr. Jekyll and Ms Hide.

PMID- 17508432
TI  - What do we know about insulin resistance and glucose metabolism in patients with
      schizophrenia treated with antipsychotics?

PMID- 17508434
TI  - Gem of an idea for a unique machine.

PMID- 17508435
TI  - National Preparedness Month 2006.

PMID- 17508436
TI  - The "de-professionalization" of dentistry.

PMID- 17508437
TI  - It's hip to be square!

PMID- 17508439
TI  - Progress towards the 2005 international targets for tuberculosis control.

PMID- 17508438
TI  - Outbreaks of Rift Valley fever in Kenya, Somalia and United Republic of Tanzania,
      December 2006-April 2007.

PMID- 17508440
TI  - [Resection and grafting of abdominal aorta during removal of sigmoid colon cancer
      metastasis into paraaortic lymphatic nodes].

PMID- 17508441
TI  - [Removal of tumor thrombus from right auricle and inferior vena cava at patient
      with leiomyomatosis].

PMID- 17508442
TI  - [Do chorea and ballism constitute poles of a symptom continuum?].

PMID- 17508443
TI  - [The 82nd annual meeting of the Japanese Society for Tuberculosis. Osaka, Japan.
      June 5-6, 2007. Abstracts].

PMID- 17508444
TI  - [The 108th congress of the Japanese Society of Otolaryngology. Kanazawa, Japan.
      May 17-19, 2007. Abstracts].

PMID- 17508445
TI  - [The 50th annual meeting of the Japanese Society of Nephrology. Hamamatsu, Japan.
      May 25-27, 2007. Abstracts].

PMID- 17508446
TI  - [The 47th annual meeting of the Japanese Respiratory Society. Tokyo, Japan. May
      10-12, 2007. Program and Abstracts].

PMID- 17508447
TI  - Reversing heart failure: the holy grail.

PMID- 17508448
TI  - Humane teaching methods in veterinary education.

PMID- 17508450
TI  - Sustained reversal of left ventricular remodeling following mechanical and
      pharmacologic therapy.

PMID- 17508449
TI  - Feminisation of the profession.

PMID- 17508451
TI  - Proceedings and abstracts of the 8th International Congress of Physiological
      Anthropology, Kamakura, Japan, October 9-14, 2006.

PMID- 17508452
TI  - Potential impact of AUSFTA on Australia's blood supply.

PMID- 17508453
TI  - [Archives and memory of the sciences: historiographical issues].

PMID- 17508454
TI  - Dowry-murder: an example of violence against women.

PMID- 17508455
TI  - [Stress, Environment and Aging. Proceedings of the 21st International Congress of
      the French-speaking Society of Psycho-geriatrics, Paris, France, 15-16 September
      2005].

PMID- 17508456
TI  - Controlling rabies: call for an integrated approach.

PMID- 17508457
TI  - RCVS questioned on medicines, graduate support and veterinary nurse training.

PMID- 17508458
TI  - The early rise of small animal practice.

PMID- 17508459
TI  - Anne Conway, early Quaker thought, and the new science.

PMID- 17508460
TI  - Why the Quakers quaked: the influence of climatic change on Quaker health, 1647
      1659.

PMID- 17508461
TI  - The way we age now: medicine has increased the ranks of the elderly. Can it make
      old age any easier?

PMID- 17508462
TI  - Democrats likely to step up oversight.

PMID- 17508463
TI  - Creating a paperless nursing facility.

PMID- 17508464
TI  - Residents have hand in expansion.

PMID- 17508465
TI  - Mary W: a nutrition case study.

PMID- 17508466
TI  - Corporate compliance revisited.

PMID- 17508468
TI  - Epidemiology of HIV infection and AIDS in Croatia--an overview.
AB  - This article presents an overview of HIV/AIDS epidemiology and surveillance in
      Croatia 20 years after the first documented case of AIDS in the country. Here we
      describe strategies employed for HIV/AIDS surveillance in Croatia as well as
      preliminary results of HIV seroprevalence among most-at-risk populations (MARPs)
      research conducted by the Infectious Diseases Epidemiology Service at the
      Croatian National Institute of Public Health (CNIPH). Croatia has a low incidence
      and prevalence of HIV and AIDS. At the end of 2005, there were 553 documented
      cases of HIV infection, 239 of which progressed to AIDS. In Croatia, AIDS is
      being registered within MARPs only and dominantly among men who have sex with men
      (MSM). AIDS patients and HIV infected persons are found in all parts of the
      country. Crude prevalence of HIV among MARPs was found to be 0.9%. It is
      necessary to continue with current prevention and control measures in the
      country, and to create a culture of awareness and precaution, a strategy that has
      proven effective in reducing risk of HIV infection.

PMID- 17508467
TI  - The epidemiology of HIV and AIDS in the world.
AB  - The worldwide epidemic of HIV continues to expand in many regions of the world,
      particularly in southern Africa, South and Southeast Asia, East Asia and Eastern
      Europe and Central Asia. Estimates are that at the end of 2005 there were 38.6
      million persons living with HIV infection and that 4.1 million new infections and
      2.8 million deaths from HIV occurred during the year. Regionally different
      patterns predominate from generalized heterosexual epidemics in sub-Saharan
      Africa and parts of the Caribbean to mixes of epidemics in which transmission
      among injection drug users, their sexual partners, commercial sex workers and
      their partners intersect. Multilateral and bilateral antiretroviral access
      campaigns, such as the World Health Organization's 3 x 5 initiative, have
      resulted in broader access to live-saving therapy for infected persons in low-
      and middle-income countries, but several million infected people who are
      clinically eligible for antiretroviral therapy remain untreated. The public
      health challenge worldwide is to keep the uninfected and to treat and care for
      those who have already been infected.

PMID- 17508469
TI  - Twenty years of human immunodeficiency virus infection in Croatia--an epidemic
      that is still in an early stage.
AB  - Croatia has a low-level HIV epidemic; 553 persons were diagnosed with HIV
      infection in the period 1985-2005. The principal mode of transmission was sex
      between men (40% of cases) and heterosexual contact (40%). Only about 10% of
      cases were injecting drug users. Testing data also suggest a low prevalence of
      HIV infection in Croatia, even in vulnerable groups. Behavioral data indicate
      risky sexual behaviors, with the clear need for interventions. National policy
      towards HIVIAIDS is operated through the National Committee on HIV/AIDS, a
      multisectorial advisory body to the Government of Croatia. Croatia applied to the
      Global Fund to fight AIDS, tuberculosis and malaria in 2002 which resulted in a
      4,9 million USD grant for scaling up prevention interventions. Croatia has a
      centralized system of treatment and care which is provided at the University
      Hospital for Infectious Diseases in Zagreb. Highly active antiretroviral
      treatment is provided free of charge from April 1998.

PMID- 17508470
TI  - HIV-1 subtype B epidemic and transmission patterns in Slovenia.
AB  - In the present study the epidemic of human immunodeficiency virus type 1 (HIV-1)
      subtype B in Slovenia during the 10-year period was investigated using
      phylogenetic analysis of pol gene sequences. 119 pol sequences generated on
      samples dated from January 1996 to December 2005 were retrieved from the database
      of Slovenian HIV/AIDS Reference Laboratory. The phylogenetic analysis revealed 14
      potentially significant transmission clusters (bootstrap value > or = 98%),
      comprising 34 HIV-1 strains. The vast majority of clustered individuals were men
      (91%), and of them, 79% were men who have sex with men. Factors significantly
      associated with clustering were: recent infection (HIV-1 infection during or
      after year 2003), diagnosis of primary HIV-1 infection, higher CD4 cell count and
      acquiring HIV-1 infection in Slovenia. Recent subtype B HIV-1 infections are the
      important driving force of current HIV-1 epidemic in Slovenia.

PMID- 17508471
TI  - Persistant immunodominant anti-gag SLYNTVATL responses in HIV-patients with up to
      7 years of HAART.
AB  - We analyzed Gag-specific CD8+ T-cells in HIV-patients on long-term HAART and in
      untreated chronically-infected patients by using iTAg MHC class I tetramers (HLA
      A*0201) specific for SLYNTVATL. Gag SLYNTVATL-specific CD8+ T-cells were
      detectable in 18 of 26 treated patients (median 5.2 years of HAART) and in 10 of
      14 untreated patients. Median percentage of Gag SLYNTVATL-specific CD8+ T-cells
      in treated patients was 0.10 (range 0.00-0.70%). Median number of Gag SLYNTVATL
      specific CD8+ T-cells per 50,000 CD8+ T-cells was 56.0 cells (range 2.0-344.0
      cells) and was not significantly different compared with untreated patients (p =
      0.978). Numbers of Gag SLYNTVATL-specific CD8+ T-cells were inversely correlated
      with the duration of undetectable plasma viremia (p = 0.02, Rho = -0.430).
      Chronically-infected HIV-patients on HAART (for up to 7.7 years) maintained a
      stable subpopulation of Gag SLYNTVATL-specific CD8+ T-cells. This finding is
      relevant for the analysis of treatment-induced immune reconstitution and,
      possibly, for future therapeutic strategies in HIV-disease.

PMID- 17508472
TI  - Blood-stained letter received by HIV/AIDS reference laboratory in 1993--a
      historical case report.
AB  - We describe an interesting historical case of a blood-stained letter received in
      1993 by Slovenian HIV/AIDS Reference Laboratory. According to the statement of
      the sender, the letter was spotted with HIV-infected blood. The polymerase chain
      reaction (PCR) amplification with two gag and env primer sets excluded the
      presence of HIV proviral DNA in the spot punches obtained from the dried blood
      spots. Although the presence of HV DNA was confirmed in 5 positive control blood
      spots using the same sets of primers, we still doubted in the accuracy of the HIV
      negative result. Fortunately, we obtained a serum sample of the author of the
      letter four months later from a psychiatric institution where he was hospitalized
      for paranoid schizophrenia. Since no anti HIV-1/2 antibodies were detected in his
      serum sample, our initial HIV negative findings based on PCR testing of blood
      spots were confirmed.

PMID- 17508473
TI  - False-positive result of a confirmatory human immunodeficiency virus line immuno
      assay in an apparently healthy individual--a case report.
AB  - A case of a false-positive result of human immunodeficiency virus (HIV)
      confirmatory immunoblot-based assay is described. Repeatedly borderline reactive
      anti-HIV screening enzyme immunoassay result obtained in a local hospital
      resulted in directing the sample to the Slovenian HIV/AIDS Reference Laboratory.
      In the Reference Laboratory, both anti-HIV screening assays and confirmatory
      Western blot were negative, while a confirmatory test INNO-LIA HIV I/II Score
      (Innogenetics, Ghent, Belgium) was anti-HIV-1 positive due to sgp120 and gp41
      reactivity. The results of serological testing of the second sample obtained
      three weeks later were completely identical, while in the third sample obtained 5
      months later, seroreversion was observed. Due to a negative dynamics in anti-HIV
      serological profile and repeatedly negative results of the molecular tests for
      HIV-1 and HIV-2, HIV infection was excluded and the results of test INNO-LIA HIV
      I/II Score were finally interpreted as false positive.

PMID- 17508474
TI  - Clinical features and virologic characteristics of primary and early HIV-1
      infection in Slovenian patients.
AB  - Analysis of time trends in newly diagnosed HIV-1 infected patients in Slovenia
      over a 10-year period (1996-2005) showed an increase in the number of newly
      diagnosed HIV-1 infected patients in 2004 and 2005 as well as increase in the
      number of newly diagnosed patients with primary/early HIV-1 infection. A
      retrospective analysis was performed in order to evaluate the clinical,
      epidemiological, laboratory and virological parameters of primary/early HIV-1
      infection presenting with or without acute retroviral syndrome (ARS).
      Primary/early HIV-1 infection was diagnosed in 33 (19.5%) out of 169 newly
      diagnosed HIV-1 infected patients during the 10-year period. Most patients
      experienced ARS, the most commonly reported symptoms being fever, malaise and
      pharyngitis, followed by rash and lymphadenopathy. Median CD4 cell count was 415
      cells/mm3, median CD8 cell count was 865 cells/mm3 and median HIV-1 viral load at
      the time of diagnosis was 5.1 loglo copies/mL. The increase in the number of
      newly diagnosed HIV-1 infected patients may be in part due to increased awareness
      among clinicians of the possibility of ARS, and the possibility of increased
      awareness of symptoms of ARS among persons at high risk of infection.

PMID- 17508475
TI  - Tuberculosis in HIV-infected patients in Croatia between 1986 and 2005.
AB  - A retrospective medical chart review was performed on 65 HIV-infected patients
      with tuberculosis hospitalized between 1986 and 2006 at the University Hospital
      for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb. Thirty two patients
      presented with pulmonary involvement, 13 with extrapulmonary, and 20 patients had
      disseminated tuberculosis. Forty five patients had an abnormal chest X-ray.
      Mycobacterium tuberculosis was identified in 35 (53.9%) patients. Ten (15.3%) of
      65 patients had already been receiving antiviral therapy, while another 31
      (47.7%) initiated antiviral therapy after antituberculosis therapy. Tuberculosis
      associated immune reconstitution inflammatory syndrome was observed in 11/27
      (40.7%) patients. Forty one patient received the standard six month course of
      antituberculous therapy, while in 12 patients the therapy was prolonged. Twenty
      one patient (32%) experienced an adverse event to antituberculosis drugs. Twelve
      patients died (18.5%). After the introduction of highly active antiviral therapy
      (HAART) the mortality decreased. The incidence of tuberculosis in HIV-infected
      patients in Croatia is increasing, and tuberculosis is still an important
      opportunistic infection in our HIV-infected patients.

PMID- 17508476
TI  - HIV-associated lipodystrophy syndrome.
AB  - In recent years, lipodystrophy and its related complications have become one of
      the major problems confronting HIV-infected patients on antiretroviral therapy.
      More than ten years after having been described for the first time, comprehensive
      knowledge of its underlying molecular basis, the natural history of body fat
      changes and metabolic abnormalities, and even a working definition of
      lipodystrophy are all still lacking. No standardized objective assessment of body
      fat has been incorporated into clinical practice for patient monitoring. Although
      a huge amount of data has been generated, no clinically proven treatment for any
      feature of lipodystrophy is currently available. The only intervention that has
      been shown to reverse lipoatrophy had been the discontinuation of thymidine
      analogues, although even then the results obtained are at most partial or modest.
      Recently published studies using uridine (NucleomaxX) and pravastatin resulted in
      a significant increase of subcutaneous fat. The potential for reversing
      lipodystrophy once it has developed is limited, but promising results in
      preventing it are obtained with thymidine analogue-sparing initial antiretroviral
      regimens. These results raise the question of whether we may be facing a
      definitive solution to the lipodystrophy syndrome.

PMID- 17508477
TI  - Patterns of sexual behaviour and reported symptoms of STI/RTIs among young people
      in Croatia--implications for interventions' planning.
AB  - This paper describes some of the results of the first national-level survey on
      sexual behaviour and the distribution of risks to sexually transmitted infections
      (STIs), including human immunodeficiency virus infection (HIV), among youth in
      Croatia, and the nature and the extent of their vulnerability to these adverse
      health outcomes. The study was a cross-sectional, probability-based household
      survey conducted in 2005, and included 1093 respondents aged 18-24. This paper
      aims to describe the findings related to the knowledge of HIV transmission, key
      behavioural outcomes relevant for potential transmission of HIV and STIs, and
      correlates of genital discharge in young men and young women. More than 80% of
      young people know that the correct use of condoms protects against HIV and that
      HIV can be transmitted by someone who looks healthy. Fifty-nine percent of young
      men and 52.4% of young women reported using condoms during the first sexual
      intercourse, and 59.3% of men and 46.1% of women used condoms during the last
      sexual intercourse with a casual partner. This points to the gap between
      knowledge of condom use and the actual use of condoms as a high proportion of
      risky sexual contact remain unprotected. Having sexual intercourse frequently or
      regularly while consuming alcohol was reported by 19.2% of men and 7.6% of women.
      Much lower proportion are using drugs frequently or regularly during sexual
      intercourse (3.7% of men and 2.1% of women). Among those sexually experienced,
      11.8% of men and 44.1% of women reported ever having a genital discharge. Higher
      presence of genital discharge in women is suggestive of reproductive tract
      infections that are not necessarily sexually transmitted. In the multivariate
      analysis, the lack of knowledge of whether chlamydial infections is an STI and
      having more than five partners in life were correlates of genital discharge in
      men, while in women the correlates included having more than five partners in
      life and not using condoms during the first sexual intercourse. Higher burden of
      STI-related symptoms was found among men who have men as sexual partners, those
      who paid for sex, and those with concurrent partnerships. These findings point
      out to the immediate need to strengthen sexual health education among young
      people and to the necessity for further development of other broad-based
      interventions to prevent adverse sexual health outcomes among both men and women,
      as well as those targeted towards more vulnerable subgroups.

PMID- 17508478
TI  - Condom use and its consistency among metropolitan high school students in
      Croatia, 1997-2001: has anything changed?
AB  - Sexually active adolescents face serious health risks associated with unprotected
      sexual intercourse, such as HIV infection and other sexually transmitted diseases
      (STDs), as well as unwanted pregnancy. To assess protective behavior among urban
      adolescents in Croatia we surveyed over 4000 high-school students, 15-19 years of
      age, in two waves: 2070 in 1997 and 1972 in 2001. The survey was carried out in
      various types of secondary schools in the capital city. The analyses suggest
      statistically significant increase in HIVIAIDS related knowledge in the observed
      period. A slight but significant increase was also observed in the acceptance of
      condom use. Both changes were more substantial among female students. In regards
      to protective behavior, we found significant increase in condom use, as well as
      in its consistency. Still, a large proportion of students did not use condom at
      last sexual intercourse (40% in 2001). In addition to generational effect, number
      of sexual partners, sexual victimization and mother's education (only in the case
      of young women) were identified as correlates of condom use consistency. While
      mother's education had positive effect, having 4 or more partners and having
      survived sexual violence decreased the likelihood of consistent condom use. In
      conclusion, the authors discuss the relevance of systematic school-based
      prevention of sexual risk taking among Croatian adolescents.

PMID- 17508479
TI  - Quality of life of HIV-infected persons in Croatia.
AB  - The aim of this study was to examine health-related quality of life among
      Croatian HIV infected individuals, and to assess the impact of socio-demographic
      and disease-related variables on health-related quality of life. This was a
      crosssectional study of 111 HIV-infected adults who received care at the
      University Hospital for Infectious Diseases in Zagreb, Croatia. The World Health
      Organization Quality of Life Questionnaire for HIV brief version (WHOQOL-HIV
      BREF) was used to assess each patient's quality of life. Ratings of quality of
      life differed across age, marital status, level of education, health status and
      "currently ill" status. Subjects who perceived themselves as not ill and their
      health status as better reported better quality of life for all quality of life
      domains (p < 0.01). Subjects who were in relationships gave higher ratings for
      the social relationships domain (p < 0.01). Subjects with higher level of
      education gave significantly higher ratings within the independence (p < 0.05)
      and environment (p < 0.01) domains. Younger subjects perceived their
      psychological state as better (p < 0.05). The findings demonstrate a moderate
      degree of overall quality of life (X = 112.2; SD = 18.92) with main concerns
      related to social relationships. These results highlight the need for better
      access to psychosocial support and medical and legal services for people living
      with HIV/AIDS in Croatia.

PMID- 17508480
TI  - Prevalence of moderate and severe depression among Croatian patients infected
      with human immunodeficiency virus.
AB  - The aim of the study was to assess the prevalence of depression among Croatian
      patients infected with human immunodeficiency virus (HIV) and to make a
      comparison with patients with other acute and chronic infectious diseases. We
      assessed the depressive disorder using the Beck Depression Inventory
      questionnaire (BDI), without clinical confirmation. The BDI scores were examined
      in 80 HIV-infected persons and compared to 80 persons with chronic viral
      hepatitis and 78 with acute infectious diarrhea. All examinees were treated as
      outpatients at the University Hospital for Infectious Diseases in Zagreb in March
      and April of 2003. Prevalence of moderate and severe depression among HIV
      infected was 16/80 (20%) with a 95% confidence interval 11% to 29%. Male patients
      with HIV or chronic viral hepatitis had a significantly higher BDI scores than
      males with acute infectious diarrhea (p = 0.017, Kruskall-Wallis, d.f. 2). Female
      patients with HIV infection tended to have a lower BDI score than females with
      chronic viral hepatitis or acute infectious diarrhea (p = 0.087, Kruskall-Wallis,
      d.f. 2). Prevalence of moderate and severe depression among Croatian HIV-positive
      patients is higher than the upper estimate for general population. Croatian males
      with chronic infectious disease have higher rate of depression than those with
      acute infectious disease.

PMID- 17508481
TI  - Attitudes towards HIV/AIDS among four year medical students at the University of
      Zagreb Medical School--better in 2002 than in 1993 but still unfavorable.
AB  - Fourth-year medical students at Zagreb University School of Medicine were
      surveyed about their knowledge and attitudes regarding HIV/AIDS in 2002/03 and
      this was compared to a student generation studying during 1993/94. Results
      indicated that the 2002/03 students scored significantly higher then did 1993/94
      students on knowledge, and attitudes towards HIV/AIDS. However, 84% of 2002/03
      students believed that health care workers (HCW) have the right to know the HIV
      status of their patients, 50% would disclose the HIV status to another HCW
      against patient's wishes and only 35% believed that HIV testing should be
      voluntary. The following factors were independently associated with a more
      favorable attitude towards HIV/AIDS: less homophobia (beta = -0.37, p < 0.001),
      experience with HIV/AIDS patients (beta = 1.02, p < 0.001), better knowledge
      about transmission (beta = 0.18, p = 0.016), and 2002/03 academic year (beta = 
      1.45, p = 0.011). Despite improvements, some negative attitudes towards HIV/AIDS
      remained prevalent in 2002/03.

PMID- 17508482
TI  - On the road: Croatian truck drivers, commercial sex and HIV/AIDS.
AB  - The primary aims of this study were to examine Croatian truck drivers' sexual
      contact with sex workers, estimate the frequency of condom use, and assess
      knowledge of HIV/AIDS within this population. The research was conducted from
      June 14 to September 16, 2005 at customs offices and accompanying parking lots in
      four Croatian cities. The sample consists of 69 truck drivers. Information about
      sexual behavior and condom use were gathered by using a semi-structured
      interview. Knowledge of HIV/AIDS, measured with a self-administered
      questionnaire, was found to be low. Six respondents (8.7%) had correctly answered
      all 13 questions. By contrast, 73% of drivers considered themselves well informed
      about HIV/AIDS, indicating that most drivers overestimate their knowledge. The
      majority of respondents (n=62) assumed that most of their colleagues engage in
      sexual contact with sex workers while on the road, although only one third of
      respondents reported that they personally have paid for sex. All of the
      respondents who reported engaging in sexual contact with sex workers stated that
      they always use condoms. Fear of being infected with a sexually transmitted
      infection was reported as the main reason for condom use.

PMID- 17508483
TI  - HIV/AIDS and Croatian migrant workers.
AB  - Due to their geographical mobility and long periods of separation from intimate
      partners, migrant workers are at increased risk for a variety of sexually
      transmitted infections (STIs) including HIV/AIDS. This study sought to
      investigate patterns in HIV/AIDS related knowledge, attitudes and sexual
      behaviour in migrant workers in Croatia. In 2003, 566 male migrant workers were
      recruited during regular required medical examinations and surveyed at seven
      locations throughout the country. Each participant was asked to complete a self
      administered KABP (sexual knowledge, attitudes, beliefs and practices)
      questionnaire. The average age of respondents was 38.2 years and the majority
      worked as seafarers (77.3%) and construction workers (20.5%). Only 18.5% of
      respondents were able to correctly answer all 13 questions assessing knowledge of
      HIV/AIDS. Seafarers reported higher levels of knowledge than did construction
      workers. The average respondent reported having had two sexual partners in the
      last 12 months, with slightly over half of the respondents (55.3%) reporting
      condom use at their last intercourse with a casual partner. One fifth of the
      respondents (20.3%) who reported having had intercourse with a sex worker during
      the last year reported not using condoms at last intercourse. The number of
      sexual partners was correlated with age, marital status, faith in God, and
      personal HIV risk assessment. Attitudes toward condom use, co-workers' HIV/AIDS
      concerns and the duration of migrant status (within the last two years) were
      shown to be significant correlates of condom use at last intercourse with a
      casual partner. The effect of HIV/AIDS related knowledge on analyzed behaviors
      did not reach statistical significance. Inadequate patterns of migrant workers'
      condom use, gaps in knowledge about HIV transmission and modes of protection, as
      well as widespread ignorance regarding available anonymous HIV testing found by
      this study suggest a critical need for expert intervention to avert the potential
      for an increase in new HIV/AIDS cases. A coordinated, systematic campaign for
      HIV/AIDS prevention among Croatian migrant workers should focus on increasing
      peer communication about HIV/AIDS, especially among younger migrant workers, and
      on reducing the frequency of sexual risk taking.

PMID- 17508484
TI  - Characteristics of clients tested for human immunodeficiency virus infection at
      the Voluntary Counselling and Testing Center in Zagreb, Croatia.
AB  - The objective of this study was to present some epidemiological characteristics
      of persons tested for HIV/AIDS at the Voluntary Counselling and Testing Centre
      (VCT) Zagreb that was founded in November 2004. The majority of clients tested
      were between 25 and 29 years old and had a secondary level education. 78% of the
      clients tested reported one risky behaviour in the past, the majority of which
      was attributed to risky heterosexual behaviour (having unprotected sexual
      intercourse). 35% of the clients reported having never or only occasionally used
      condom with a non-regular partner. 30% of the clients with a history of injecting
      drug use reported that they never "shared" injecting equipment. The results
      presented in this paper could be a useful tool for public health officers when
      targeting interventions for HIV prevention.

PMID- 17508485
TI  - HIV-infected children in Croatia--medical care versus ethical and social issues.
AB  - The era of pediatric HIV-infection in Croatia began in 1987 when the first child
      from an HIV-infected mother was born. The authors present some medical data of
      children diagnosed as HIV-infected or observed because of maternal HIV-infection
      in Croatia until the end of 2005. Although the number of HN-infected children in
      Croatia is still relatively small, in the last two decades the Croatian society
      was confronted with many ethical and social issues regarding HIV-infection and
      discrimination. There were many obstacles in providing proper care and
      integrating HIV-infected children in the Croatian society. Stigmatisation, fear
      and lack of knowledge were major contributors. For the first time, the
      integration of an HIV-infected child with revealed HIV-status into school was
      described. Changes in attitudes towards HIV-infected people can only be achieved
      through planned permanent educational programs.

PMID- 17508486
TI  - Prevalence of chlamydial genital infection and associated risk factors in
      adolescent females at an urban reproductive health care center in Croatia.
AB  - The study was undertaken to determine the prevalence of chlamydial genital
      infection in sexually active, urban adolescent females 15-19 years; to identify
      behavioral, demographic, and clinical factors associated with chlamydial
      infections; and to develop criteria for potential screening strategies. 500
      adolescent women, median age 17.7 years, who visited gynecological outpatient
      clinic in Children's Hospital Zagreb for different reasons were enrolled in this
      study. Gynecological exam, colposcopy, detection of chlamydial infection by the
      rapid direct immunoassay of endocervical swab (Clearview Chlamydia-Unipath),
      endocervical cytological examination--Papanicolaou smear, and questionnaire to
      obtain demographic, social, behavioral and presence of symptoms data were
      performed. Positive Chlamydia trachomatis test were found in 16.4% of
      participants, cytologic cervical abnormalities--cervical intraepithelial
      neoplasia (CIN I-CIN III) were found in 25.2% and cytological signs of Human
      papilloma virus were found in 11.4%. Stepwise multivariate logistic regression
      analysis identified five factors associated with infection: the age of menarche <
      or =13 years, > or =4 lifetime sexual partners, non-use of contraception (rare or
      never), cervical friability, and abnormal Papanicolaou test. Urban adolescent
      sexually active women are at high risk for chlamydial infection and other
      sexually transmitted diseases including HIV infection. Association between
      chlamydial genital infection and risk-taking sexual and contraceptive behavior
      was found. Routine Chlamydia trachomatis testing for this population is
      recommended as well as implementation of school based sexual health education
      because of their risk-taking sexual behavior.

PMID- 17508487
TI  - Distribution of hepatitis C virus genotypes in Croatia--a 10 year retrospective
      study of four geographic regions.
AB  - The aim of this 10-year retrospective study was to investigate the distribution
      of HCV genotypes in patients with chronic hepatitis C monitored in the largest
      center for molecular diagnostics of HCV infection in Croatia. The study enrolled
      1163 anti-HCV positive adults with detectable HCV RNA in the plasma. The patients
      were classified in four regions: Zagreb and surrounding continental area, Split,
      Slavonija and Rijeka. HCV genotyping was performed by using VERSANT HCV
      Genotyping Assay (LIPA) (Bayer Diagnostics, Puteaux Cedex, France). Statistical
      analysis was performed by using Statistica for Windows V.5.1. The majority of HCV
      infections in the study population were caused by genotypes 1 (58.8% of infected
      patients) and 3 (35.6%). Percentages of patients infected with subtypes 1b and 1a
      were 37.4% and 13.1%, respectively. Genotypes 2 and 4 were present in a very low
      percentage of patients (2.2% and 3.4%, respectively) while genotypes 5 and 6 were
      not detected. Analysis of regional differences in the distribution of HCV
      genotypes revealed similar percentages of subtype 3a and 1b infections in the
      Split region while the majority of infections in other regions were caused by
      subtype 1b. Infections with genotypes 2 and 4 were present in less than 5% of
      patients in all geographic regions. Analysis of an association between risk
      factors for infection and distribution of genotypes and subtypes in a subset of
      patients from the Split region confirmed the association between IVDU and subtype
      3a. We conclude that the prevalence of HCV genotypes and subtypes follows the
      pattern of other Southern and Eastern European Countries with the predominance of
      subtypes 1b, 3a and 1a.

PMID- 17508488
TI  - Etiology of chronic prostatitis syndrome in patients treated at the university
      hospital for infectious diseases "Dr. Fran Mihaljevic" from 2003 to 2005.
AB  - A total of 835 patients with symptoms of chronic prostatitis syndrome and no
      evidence of structural or functional lower genitourinary tract abnormalities were
      examined in a three year period at the Outpatient Department for Urogenital
      Infections, University Hospital for Infectious Diseases "Dr. Fran Mihaljevic"
      Zagreb, Croatia. Disease etiology was determined in 482 (57.72%) patients.
      Chlamydia trachomatis was proved to be the causative pathogen in 161 patients,
      Trichomonas vaginalis in 85, Escherichia coli in 68, Enterococcus in 51, Proteus
      mirabilis in 20, Klebsiella pneumoniae in 9, Streptococcus agalactiae in 15,
      Ureaplasma urealyticum in 49 patients with chronic prostatitis. Other patients
      had mixed infection. In 257 (53.32%) of 482 patients, the inflammatory finding
      (>10 WBCs/hpf) was found in EPS or VB3. Normal WBCs/hpf (<10) was found in 103
      (63.98%) of 161 patients with symptoms of chronic prostatitis in whom C.
      trachomatis was detected in EPS or VB3, in 50 (58.82%) of 85 patients in whom
      Trichomonas vaginalis was isolated, and in 23 (46.94%) of 49 patients in whom
      Ureaplasma urealyticum was isolated.

PMID- 17508489
TI  - The role of school medicine doctors in health education in Croatia--past, present
      and future.
AB  - Croatia never had a separate vocation (occupation) of a health educator. Health
      education is one of the main tasks in the long tradition of preventive work of
      doctors-school medicine specialists. Additionally, in the school curriculum in
      the Republic of Croatia the health-educational contents are integrated into
      various subjects, and are conducted by teachers. However, there are requests to
      introduce a new subject into schools called Health Education. We asked physicians
      of school medicine their opinion on the introduction of this new subject. 30% of
      the physicians were dissatisfied with the current condition, 10% were satisfied,
      while there were no very satisfied school medicine doctors. They believe that
      health education goals are oriented solely to passing on knowledge (facts), while
      efforts are not done to change habits and attitudes of young people. They
      recognize themselves as persons mostly involved in health education in schools.
      Half of the school medicine doctors believe that the school curriculum should
      contain both a separate subject as well as integration of health education into
      other subjects. Before introducing any changes into healthcare or education
      system, it is necessary to examine the attitudes of students and parents, to
      direct the changes towards the promotion of the cooperation between the
      healthcare system, education, civil society, school and community where investing
      into the health of young people is done through comprehensive and holistic
      programmes.

PMID- 17508490
TI  - The diagnosis and treatment of human papillomavirus-mediated genital lesions.
AB  - Genital warts (condyloma acuminatum, venereal warts) are common highly contagious
      benign epithelial lesions occurring on the genitals, perianal area, and inguinal
      folds, and are caused by human papillomavirus (HPV). Diagnosis is based largely
      on the clinical appearance of lesions. New home-based treatments, including
      podofilox and imiquimod, have revolutionized the therapeutic management of
      genital warts, empowering patients to participate in their own treatment with
      products that primarily have local side effects. This article reviews the
      diagnosis and treatment (office based and home based) of genital warts.

PMID- 17508491
TI  - Treatment of molluscum contagiosum and herpes simplex virus cutaneous infections.
AB  - Molluscum contagiosum (MC) is a human viral infection contracted by skin-to-skin
      inoculation, autoinoculation, and fomite inoculation. There are a variety of
      treatments for MC, including watchful waiting, curettage, cantharidin,
      cryotherapy, and topical imiquimod. Herpes simplex virus (HSV) infections also
      have been treated with imiquimod. This article discusses the treatment of MC and
      HSV infections and reviews the literature.

PMID- 17508492
TI  - Topical therapy in the treatment of actinic keratosis and basal cell carcinoma.
AB  - Actinic keratosis (AK) is an evolving malignant cutaneous neoplasm. AK also is
      known as solar keratosis and squamous cell carcinoma (SCC) in situ, either solar
      keratotic type or keratinocytic intraepidermal neoplasia. AKs can be treated with
      destructive or topical therapies. This article reviews current and evolving
      topical therapeutic options for AKs, several of which have been shown to offer
      substantial benefit in the alleviation of these lesions. The topical therapies
      include 5-fluorouracil (5-FU), diclofenac sodium, colchicine, retinoids, and
      imiquimod. Topical treatment of basal cell carcinoma (BCC) with imiquimod also
      will be discussed.

PMID- 17508493
TI  - The treatment of viral infections and nonmelanoma skin cancers.
AB  - Immunomodulatory therapy, which functions to upregulate immune response, may be
      directed against a variety of disease states, including viral infections and skin
      malignancies. Examples of immune response modifiers include injectable interferon
      (IFN) and topical imiquimod. Topical imiquimod has been studied for a variety of
      different disorders including human papillomavirus infection, molluscum
      contagiosum, actinic keratosis (AK), squamous cell carcinoma (SCC) in situ,
      superficial basal cell carcinoma (sBCC), nodular basal cell carcinoma (nBCC), and
      lentigo maligna. Case reports also have demonstrated use for select cases of
      extramammary Paget disease. This article focuses on therapies designed to augment
      immune response to treat viral infections and nonmelanoma skin cancers and
      reviews clinical applications, efficacy, recommended treatment regimens,
      monitoring of response, and avoidance of pitfalls associated with the use of
      topical imiquimod.

PMID- 17508494
TI  - Mechanism of action and other potential roles of an immune response modifier.
AB  - Imiquimod (1-[2-methylpropyl]-1H-imidazo[4,5-c]quinolin-4-amine) is a widely used
      topical immune response modifier. This drug was initially developed as an
      antiviral agent and was found to have potent effects on the immune system.
      Because imiquimod causes the activation of antigen-presenting cells (APCs), it
      acts as an immunologic adjuvant. By triggering cytokine production, imiquimod
      enhances the ability of APC to present viral or tumor antigens to reactive T
      lymphocytes, and amplifies type 1 helper T cell (T(H) 1)-mediated immune
      responses (interferon [IFN] gamma production as well as other related cytokines).
      The cellular receptors for imiquimod and its analogues are toll-like receptors
      (TLR) 7 and 8. These 2 receptors are part of a larger family of TLRs that are
      critical components of innate immunity, which has evolved to detect dangerous
      bacterial, viral, fungal, and parasitic infections. Topical imiquimod is a U.S.
      Food and Drug Administration (FDA)-approved treatment for external genital warts,
      actinic keratoses (AKs), and superficial basal cell carcinomas (sBCCs). Because
      there are a number of cell types that express either TLR7 or receptors for
      cytokines induced by imiquimod, this agent has broad-reaching direct and indirect
      effects in the skin as well as the related skin immune system. Thus, imiquimod
      has been demonstrated to be useful in the treatment of a number of conditions
      beyond the FDA-approved indications (mostly neoplastic and infectious but also
      fibrotic and some degenerative conditions).

PMID- 17508495
TI  - Management of cancer pain with complementary therapies.
AB  - Pain is one of the most feared consequences of cancer. Pain is a major symptom in
      75% of hospitalized cancer patients. Poorly relieved pain contributes to the
      suffering of the patient and family, which may motivate them to seek additional
      complementary and alternative therapies. Evidence-based complementary therapies
      are being used for symptom control and to improve quality of life. There is
      recent research on several complementary therapies-acupuncture, mind-body
      therapies, massage, reflexology, and Reiki--that provides evidence for pain
      management. These therapies are not well utilized due to a lack of information on
      benefits, risks, and resources. There is a call for education to alert patients,
      families, nurses, and physicians to the benefits of evidence-based complementary
      therapies and to the dangers of "unproven" cancer therapies. Oncology nurses are
      ideally positioned to assess patients' pain, to educate patients, to determine
      with the patient and physician the most appropriate and safe complementary
      therapy for pain, to refer patients to appropriate resources, and in some cases
      to provide the therapy itself. This article will discuss specific complementary
      therapies for pain control and will arm nurses with the confidence to intervene
      with knowledge, referrals, and ideas for hands-on implementation.

PMID- 17508496
TI  - Upper limb swelling following mastectomy: lymphedema or not?
AB  - Having experienced an excisional biopsy, sentinel lymph node biopsy, and
      mastectomy, BH is at lifetime risk of developing post-breast cancer lymphedema in
      the arm on the side where her breast cancer was treated. She has two additional
      risk factors, among those documented in the literature: history of an infection
      (specifically a systemic infection, significant in that it required
      hospitalization for intravenous antibiotics) in the postsurgery period, and a
      moderate increase in bilateral limb volume and weight (body mass index) over the
      months and years following the breast cancer diagnosis. Further, the patient
      reported transient hand swelling on the affected side and gradual weight increase
      are cues indicating a need for patient vigilance and careful monitoring by the
      health-care team. Preventing future infections, managing weight at an optimal
      level, and preventing trauma or injury to the affected arm and chest are
      important self-management precautions to reduce risk of chronic lymphedema
      development. BH needs continued support in reviewing evidence-based risk
      reduction guidelines and understanding ways to apply them to her lifestyle. In
      the absence of preoperative baseline or contralateral limb measurements (with
      circumferences or perometry or water displacement), assessment of limb change at
      a level identified as diagnostic of lymphedema (commonly, 200-mL volume or 2-cm
      girth increase from baseline or as compared to the contralateral limb) is very
      challenging. Without bilateral preop limb measurements for baseline and
      contralateral limb comparisons, BH might have been diagnosed with lymphedema at
      postop or at 48 months, when both limbs increased symmetrically. Symptom
      assessment is also crucial, as symptom report of heaviness and swelling is found
      to be associated with limb volume changes indicative of lymphedema. Transient
      hand swelling may be evidence of latent lymphedema and cause for increased risk
      reduction education and vigilance in assessment for emergence of nonresolving
      chronic lymphedema. million American women are breast cancer survivors. According
      to the American Cancer Society, every person treated for cancer with lymph node
      removal, surgery, or radiation has a lifetime risk for lymphedema, swelling
      caused by an increase in protein-rich interstitial fluid. Some will develop
      lymphedema soon after cancer treatment (within weeks or months) and others may
      not experience

PMID- 17508498
TI  - Hurricane-hit practice offers lessons in disaster planning.

PMID- 17508497
TI  - Management of delirium.
AB  - Oncology providers are faced with delirium on a daily basis in both the inpatient
      and outpatient settings. Using appropriate screening tests and a comprehensive
      delirium safety protocol can empower both providers and family members and assist
      in the protection of patients. While delirium cannot always be prevented,
      knowledge of its pathophysiology, prevention, and treatment strategies can
      minimize the effects and possibly shorten the duration. Treating Ms. B's delirium
      and agitation allowed her to spend her remaining time peacefully with her family.

PMID- 17508499
TI  - Infection in a leukemia patient.

PMID- 17508500
TI  - Exercise regimen reduces fatigue.

PMID- 17508501
TI  - Programs work toward transitioning survivors to primary care.

PMID- 17508502
TI  - Communicating with oncology patients about palliative care.
AB  - Achieving expertise in communication requires a long-term commitment. There are
      many strategies available for nurses seeking to accomplish this task. Many online
      resources (for example, http://www.conversationsincare.com/web-bookchapter05.html
      and http://www.breakingbadnews.co.uk/) and helpful pocket cards intended to
      assist in improving communication skills are available.

PMID- 17508503
TI  - Proteasome inhibitors.

PMID- 17508504
TI  - A retrospective study of the relationship between tracheal collapse and
      bronchiectasis in dogs.
AB  - Tracheal collapse is common in middle age toy and miniature breed dogs.
      Cartilaginous defects have been identified histologically and are considered a
      form of chondromalacia. In addition to tracheal cartilaginous changes, concurrent
      lower airway histologic changes indicative of inflammation have been noted in
      dogs with tracheal collapse and these changes may lead t o concurrent
      bronchiectasis. The purpose of this study was to investigate the prevalence of
      bronchiectasis in dogs with a previous radiographic diagnosis of tracheal
      collapse. The thoracic radiographs of 60 dogs with tracheal collapse were
      evaluated for evidence of concurrent bronchiectasis. Eighteen of 60 (30%) dogs
      had evidence of bronchiectasis, and all were cylindrical in morphology. The
      signalment of affected dogs was similar to that previously reported. The
      occurrence of bronchiectasis in this group of dogs with tracheal collapse (18
      dogs) was six times higher (P < 0.05) than the expected prevalence within a
      random sample population (three dogs). The results of this study provide evidence
      of a link between tracheal collapse and bronchiectasis. A finding of
      bronchiectasis with tracheal collapse should encourage further evaluation for
      chronic lower airway disease in these patients.

PMID- 17508505
TI  - Reliability of a quantitative rating scale for assessment of horses with distal
      tarsal osteoarthritis.
AB  - Various radiographic rating scales have been described for use in horses with
      distal tarsal osteoarthritis but little information is available on their
      reliability. The aim of this study was to develop a radiographic rating scale
      based on the results of an expert consultation process (the Delphi process), and
      to test the reliability of the radiographic rating scale. Seven radiographic
      features were identified as important indicators of distal tarsal osteoarthritis
      and these were then incorporated in the radiographic rating scale, which used a
      100-mm-long visual analog scale. On two occasions nine equine veterinarians
      applied the radiographic rating scale, and a verbal descriptive rating scale, to
      three sets of tarsal radiographs, each comprising four standard radiographic
      views. Reliability was assessed using Bland-Altman plots and by calculating the
      95% agreement limits. Analysis of variance (ANOVA) was used to identify
      significant interactions between the ratings of different assessors made from
      different views and at each assessment. Rating of distal tarsal osteoarthritis
      was different for the nine assessors. The most precise second ratings were
      between 16 mm higher and 18 mm lower than the first. Significant variables were
      "joint," "assessor," and "assessment" (univariable ANOVA); and "joint and
      assessor" and "assessor and assessment" (multivariable ANOVA). The radiographic
      rating scale developed for interpretation of distal tarsal osteoarthritis was
      less reliable than a verbal descriptive rating scale.

PMID- 17508506
TI  - Development of a whole body magnetic resonance imaging protocol in normal dogs
      and canine cancer patients.
AB  - Whole body magnetic resonance imaging (whole body MR imaging) could potentially
      provide accurate cancer staging as a single imaging modality. This study was done
      to develop a whole body MR imaging protocol for a 1.5T MR instrument using four
      normal Beagle dogs (Phase 1) and then to assess the protocol's feasibility in
      cancer-bearing dogs (Phase II). In Phase I, anesthetized dogs were placed in
      dorsal recumbency with limbs flexed along the torso. T1, T2, and short tau
      inversion recovery sequences were acquired by spin echo or fast spin echo, and
      also using the more rapid single shot fast spin echo and gradient echo pulse
      sequences. Three large overlapping fields of view (FOV) were used to visualize
      the entire body and the sagittal and dorsal imaging planes were compared.
      Relative examination time, image quality, organ visibility and signal intensity
      were evaluated. Phase I results were used to establish a protocol that balanced
      image quality with examination time. In Phase II, whole body MR imaging was done
      on 10 dogs with cancer. Examination times were 60-75 min. Image quality was
      sufficient for all known lesions to be visualized, including mass lesions,
      pulmonary infiltrate, and lymphadenomegaly. Skeletal detail was sufficient to
      visualize known neoplastic lesions of the appendicular skeleton, yet it was
      suboptimal because of the large FOV and use of the body coil. Additional
      modifications of a whole body MR imaging protocol and continued technological
      improvements in MR imaging will further increase its potential for veterinary
      cancer staging.

PMID- 17508507
TI  - Preliminary evaluation of the pharyngeal constriction ratio (PCR) for
      fluoroscopic determination of pharyngeal constriction in dysphagic dogs.

PMID- 17508508
TI  - Intermittent cranial lung herniation in two dogs.
AB  - Two aged dogs with chronic obstructive airway disease were evaluated because of
      intermittent swelling of the ventral cervical region. Radiographs made at
      expiration and caudal positioning of the forelimbs allowed identification of
      intermittent cervical lung herniation of the left and right cranial lung lobe in
      both dogs. Pulmonary hyperinflation, increased expiratory effort, and chronic
      coughing were considered responsible for the lung herniation. Cervical lung
      hernia should be included in the differential diagnoses of intermittent cervical
      swelling in dogs with chronic respiratory disorders associated with increased
      expiratory effort and chronic coughing.

PMID- 17508510
TI  - Imaging diagnosis--corpus cavernosum, ischiocavernosus, and bulbospongiosus
      muscle injury in a dog.

PMID- 17508509
TI  - Echocardiographic reference values in whippets.
AB  - The aim of the study was to establish reference echocardiographic values for
      whippets, to compare these values with previously published reference values for
      the general dog population, and to determine whether there is an influence of
      gender and breeding lines on echocardiographic measurements. Echocardiographic
      parameters from 105 apparently healthy whippets without cardiac symptoms were
      used to establish reference values for the breed and to compare these values with
      two previously reported reference ranges. The coefficients of the allometric
      equation Y= aM(b), useful to reconstruct normal M-mode and two-dimensional
      average values for whippets of varying weights, were calculated, as well as the
      lower and upper limits of the 95% prediction interval. First, we found that
      whippets have a significantly larger left ventricular diameter, increased left
      ventricular wall, and interventricular septum thickness than expected, in
      diastole as well as in systole. Fractional shortening was significantly lower
      than the reference value. Second, comparing males and females, taking body weight
      differences into account, females had a significantly larger left ventricular
      diameter in diastole and systole. Minor differences were found between racing and
      show pedigree dogs. In conclusion, the results of this study confirm that breed
      specific reference values are needed in echocardiography. In whippets, the values
      found in this study can be used as references in order to avoid
      overinterpretation of cardiac dilation, hypertrophy, and/or decreased
      contractility in these dogs.

PMID- 17508511
TI  - Imaging diagnosis--canine thoracic mesothelioma.
AB  - A 12-year-old neutered female Pembroke Welsh Corgi had a 2-month history of a
      progressive, productive cough nonresponsive to therapy. Mild pleural effusion,
      right middle lung lobe collapse, and multiple subpleural nodular lesions were
      detected in thoracic radiographs and computed tomography (CT) images.
      Histopathologic diagnosis of the pleural nodules was mesothelioma. Mesothelioma
      should be considered in patients where pleural masses are detected in radiographs
      or CT images.

PMID- 17508512
TI  - Imaging diagnosis--bilateral adrenal adenomas and myelolipomas in a dog.
AB  - A 10-year-old neutered female Pug was evaluated for a left adrenal mass detected
      previously by ultrasonography. Using computed tomography, a fat-attenuating, rim
      enhancing left adrenal mass and a homogeneous, soft-tissue attenuating, intensely
      enhancing right adrenal mass were found. A left adrenalectomy and right adrenal
      biopsy were performed and the final diagnosis was bilateral adrenal adenomas and
      myelolipomas. Myelolipomas are rare, benign, endocrinologically inactive tumors
      composed of well-differentiated adipose tissue and a variable amount of
      hematopoietic cells of both lymphatic and myeloid lineages, which may account for
      the different appearance on tomographic images.

PMID- 17508513
TI  - Imaging diagnosis--intracranial epidermoid cyst in a Doberman Pinscher.
AB  - A 4-year-old Doberman Pinscher was evaluated for chronic progressive central
      vestibular disease and aggressiveness. A cyst-like lesion was identified in the
      region of the left cerebellopontine angle. The lesion was hypointense on T1
      weighted and hyperintense on T2-weighted images. Differentials included an
      epidermoid or dermoid cyst, cystic neoplasm, and brain abscess. Hyperintensity on
      subsequent fluid-attenuated inversion recovery images excluded an arachnoid cyst.
      The histopathologic diagnosis was epidermoid cyst within the fourth ventricle.

PMID- 17508514
TI  - Use of intraoperative ultrasonography in canine spinal cord lesions.
AB  - The purpose of this retrospective study was to describe the intraoperative
      appearance of various spinal cord conditions, and to investigate how
      intraoperative ultrasonography assisted in modification of surgical and
      postoperative treatment plans. Intraoperative ultrasonography (B-mode, and power
      Doppler mode) was used in 25 dogs undergoing spinal surgery. The neurologic
      conditions included cervical spondylomyelopathy, intervertebral disc (IVD)
      protrusion, IVD extrusion, spinal tumors, nerve sheath mass, granulomatous
      myelitis, and discospondylitis. All of these diagnoses were supported by
      histopathologic and/or cytologic evaluation. It was possible to visualize the
      spinal cord and the abnormal spinal tissue in all of the patients. Power Doppler
      imaging allowed assessment of the spinal cord microcirculation, and assisted in
      judgment of the degree of decompression. Ultrasound imaging directly impacted the
      surgical and the medical treatment plans in four patients. Owing to the
      intraoperative imaging, two hemilaminectomies were extended cranially and
      caudally, and additional disc spaces were fenestrated, one hemilaminectomy site
      was extended dorsally to retrieve the disc material from the opposite side, and
      one intramedullary cervical spinal cord lesion was discovered, aspirated, and
      consequently diagnosed as granulomatous inflammation, which altered the long-term
      medication protocol in that dog. This study suggests that intraoperative
      sonographic spinal cord imaging is a useful and viable technique.

PMID- 17508515
TI  - Pre- and post-treatment ultrasonography in hypothyroid dogs.
AB  - Primary hypothyroidism is a frequent endocrine disorder in the adult dog.
      However, false-positive diagnoses are common because of the relatively low
      accuracy of most commonly used biochemical tests. The purpose of this study was
      to describe the ultrasonographic features of the thyroid gland in hypothyroid
      dogs, to calculate the diagnostic sensitivity of gray-scale ultrasound using a
      combination of clinical symptoms and biochemical thyroid tests as gold standard,
      and to investigate the evolution of the ultrasonographic features after treatment
      of hypothyroidism. Eighteen dogs were studied prospectively. All dogs underwent
      an ultrasound examination at first presentation and 13 underwent one or two
      additional ultrasound examinations over time. At first presentation, a
      sensitivity of 76.5% (95% CI [50.0-93.0% 1) for decreased echogenicity, 64.7%
      (95% CI [38.385.8% 1) for inhomogeneity, 70.6% (95% CI 144.0-89.7%]) for
      irregular capsule delineation, 64.7% (95% CI [38.3-85.8%]) for abnormal lobe
      shape and 47.1% (95% CI 123.0-72.2%]) for decreased relative thyroid volume was
      obtained. Combining these five parameters together resulted in an overall
      sensitivity of 94.1% (95% CI [71.3-99.9%]) for gray-scale ultrasound in the
      detection of acquired hypothyroidism at first presentation. A continuous decrease
      of thyroid volume was seen over time after treatment, while the other
      investigated parameters did not change significantly during the follow-up period.
      None of the thyroid glands were considered normal at the last presentation.
      Grayscale ultrasound is a sensitive and quick test for the diagnosis of primary
      hypothyroidism in dogs.

PMID- 17508516
TI  - Sonographic anatomy of the palmarodistal aspect of the equine digit.
AB  - Although ultrasonography is widely used in equine orthopedics, its use in the
      distal portion of the digit is still limited. The purpose of this descriptive
      study was to document the normal ultrasonographic appearance of the palmarodistal
      aspect of the digital area imaged between the bulbs of the heels.
      Ultrasonographic images were obtained with a 7.5 MHz microconvex transducer in 10
      fresh equine cadaver forelimbs and five soundhorses. Sagittal, parasagittal, and
      transverse images were obtained from the proximal aspect of the middle phalanx to
      the distal sesamoid bone. Anatomic sections were obtained from five cadaver
      specimens to correlate the sonographic appearance with the anatomic findings. The
      remaining cadaver limbs were dissected to confirm normalcy. Ultrasonographic
      examinations were possible on all digits but distal images were more difficult to
      obtain in digits with long heels. Bony structures (palmar surface of the middle
      phalanx and proximal border of the distal sesamoid bone) and soft tissue
      structures (deep digital flexor tendon, digital tendon sheath, proximal palmar
      recess of the distal interphalangeal joint, proximal recess of the podotrochlear
      bursa, collateral sesamoidean ligaments) identified on the anatomic slices were
      seen on the matched sonographic images. Ultrasonography provides good anatomic
      details of the palmarodistal aspect of the digit. The images of this study will
      serve as a reference for clinical studies on ultrasonography of the palmarodistal
      aspect of the digit.

PMID- 17508517
TI  - Effects of sedation with midazolam and butorphanol on resistive and pulsatility
      indices in healthy dogs.
AB  - Resistive index (RI) and pulsatility index (PI) are indirect measurements of
      blood flow resistance that may be measured by pulsed wave Doppler
      ultrasonography. Chemical restrain may potentially alter the indices although it
      is required to perform ultrasonography in some patients. The purpose of this
      study was to describe values for both intrarenal and ocular RI and PI within the
      same subject in clinically normal dogs sedated with a midazolam and butorphanol
      combination and evaluate if there are any significant changes between sedated and
      nonsedated dogs. Fifteen healthy Beagle dogs were studied by Duplex Doppler
      interrogation in interlobar or arcuate arteries of the kidney and long posterior
      ciliary artery. Pulse rate and systolic blood pressure were also determined. All
      measurements were recorded before and after the administration of a sedative
      combination of midazolam (0.2 mg/kg) and butorphanol (0.2 mg/kg). Mean comparison
      tests (paired t-tests or Wilcoxon's rank-sum test) were used to determine if any
      significant differences existed between right and left renal values or right and
      left ocular values. A correlation study (Pearson or Spearman) was applied between
      RI, PI, and systolic pressure, and pulse rate. RI and PI were significantly
      higher in sedated Beagles than in unsedated Beagles. There was neither
      correlation between index and systolic blood pressure nor pulse rate. In
      conclusion, provided that normal RI and PI increase in sedated animals, then
      reference ranges should be higher when sedated--healthy or ill--animals are
      evaluated.

PMID- 17508518
TI  - Repeatability of Doppler ultrasonographic measurement of equine digital blood
      flow.
AB  - The repeatability and sensitivity of Doppler ultrasonographic measurement of
      lateral digital arterial and venous blood flow has not been previously
      determined. Doppler ultrasonography was used to measure blood flow within the
      forelimb lateral digital vessels in one normal adult Thoroughbred horse on six
      occasions and in six normal adult Thoroughbred horses on three occasions, each
      occasion being at least 1 h apart, to determine the within- and between-horse
      variation. The values obtained from the right and left lateral digital vessels
      did not differ significantly. The within-horse coefficients of variation (CV) for
      arterial and venous measurements were all acceptable (< 11%); the between-horse
      CV were acceptable (< 7%) for all parameters except TaVa (average velocity of
      first peak of arterial waveform) and TaVb (average velocity of remainder of
      arterial waveform). The within-horse intraclass correlation coefficients (ICC)
      demonstrated excellent repeatability (> or = 0.71) for all parameters except
      venous diameter; the between-horse ICC demonstrated good to excellent
      repeatability (> or = 0.67) for all parameters except TaVb. Doppler
      ultrasonography can detect differences of 0.005 and 0.01 ml/ min in digital
      arterial and venous flow, respectively, using measurements from six horses on
      three occasions (80% power; P < 0.05). Thus, the technique is sufficiently
      repeatable and sensitive to be able to detect changes in flow during different
      physiological or pathological states or following pharmacologic intervention.

PMID- 17508519
TI  - Transsplenic portal scintigraphy using 99mTc-mebrofenin in normal dogs.
AB  - Transsplenic portal scintigraphy using sodium pertechnetate is superior to per
      rectal portal scintigraphy due to improved visualization of the portal
      vasculature with decreased patient and personnel exposure. The purpose of this
      study was to describe the use of 99mTc-mebrofenin, the radiopharmaceutical of
      choice for the evaluation of hepatic function, in place of pertechnetate for
      transsplenic portal scintigraphy in normal dogs. Sixteen juvenile dogs underwent
      transsplenic portal scintigraphy using 37-130 MBq 99mTc-mebrofenin in a 0.2-0.5
      ml volume. After the initial dynamic acquisition obtained at 4 frames/s in right
      lateral recumbency, static right lateral, and ventral views were obtained at 5,
      10, 15, 20, 25, 30, 40, 50, and 60 min. A nuclear angiogram of the splenic and
      portal veins was visible in all dogs, followed by rapid distribution of the
      radiopharmaceutical in the liver. Hepatic morphology was more easily defined than
      with pertechnetate. Transit time could not be calculated due to the high hepatic
      extraction of 99mTc-mebrofenin. Mean +/- SD shunt fraction was 0.8 +/- 0.8%. Time
      to peak liver activity was 3.1 +/- 1.1 min, and hepatic excretion T1/2 was 19.4
      +/- 6.3 min. No visible blood pool and cardiac activity was seen after 5 min. The
      mean +/- SD time to visualization of defined biliary activity was 8.8 +/- 2.9
      min. Absorption from the spleen was significantly higher than that reported for
      pertechnetate (87.9 +/- 8.2%, vs. 52.5 +/- 19.1%). 99mTc-mebrofenin can be used
      in place of pertechnetate for transsplenic portal scintigraphy, with the
      advantage of combining quantitative parameters of liver function with the already
      known advantage of transsplenic portal scintigraphy.

PMID- 17508520
TI  - Comparison of isodose distributions in canine brain in heterogeneity-corrected
      versus uncorrected treatment plans using 6 MV photons.
AB  - Magnetic resonance (MR) images may be useful for radiation planning due to
      greater contrast resolution. One disadvantage of MR images for radiation planning
      is the inability to incorporate electron density information into the dose
      calculation algorithm. To assess the magnitude of this problem, we evaluated
      radiation dose distribution in canine brain by comparing computed tomography (CT)
      based radiotherapy plans with and without electron density correction.
      Computerized radiotherapy plans were generated for 13 dogs with brain tumors
      using 6 MV photons. A tissue-contouring program was used to outline the gross
      tumor volume (GTV) and the planning target volume (PTV) for each patient. Two
      treatment plans were generated for each dog. First, the plan was optimized
      without heterogeneity correction. Then the heterogeneity correction was
      implemented without changing any other plan parameters. Isodose distributions and
      dose volume histograms (DVHs) were used to compare the two plans. The D95 (dose
      delivered to 95% of the volume) within the PTV was calculated for each treatment
      plan and differences in the D95s were compared. The mean D95s without and with
      heterogeneity correction were 49.1 +/- 0.7 and 48.9 +/- 1.0Gy, respectively. The
      absolute mean percent dose difference without and with heterogeneity correction
      was 1.0 - 0.9% (-1.3-3.2%) and was not considered to be clinically significant.
      We found no clinically significant difference between CT-based radiotherapy plans
      without and with heterogeneity correction for brain tumors in small animals,
      which supports the use of MR-based treatment planning for radiotherapy of small
      animal brain tumors.

PMID- 17508521
TI  - Statistical briefing: estimating the probability of disease.

PMID- 17508522
TI  - Screening for dysplasia of the hip: weigh harms and benefits.

PMID- 17508523
TI  - Family-oriented patient care.

PMID- 17508524
TI  - Adolescent pregnancy and associated risks: not just a result of maternal age.

PMID- 17508525
TI  - Exercise is an effective intervention in overweight and obese patients.

PMID- 17508526
TI  - Tramadol relieves neuropathic pain.

PMID- 17508527
TI  - Nonpharmacologic vs. anticholinergic therapies for overactive bladder.

PMID- 17508528
TI  - Evaluation of a first seizure.
AB  - Seizure is a common presentation in the emergency care setting, and new-onset
      epilepsy is the most common cause of unprovoked seizures. The patient history and
      physical examination should direct the type and timing of laboratory and imaging
      studies. No single sign, symptom, or test dearly differentiates a seizure from a
      nonseizure event (e.g., syncope, pseudoseizure). Electroencephalography is
      recommended for patients presenting with a first seizure, and neuroimaging is
      recommended for adults. Neuroimaging also should be performed in children with
      risk factors such as head trauma, focal neurologic deficits, or a history of
      malignancy. Magnetic resonance imaging is preferred over computed tomography
      except when acute intracranial bleeding is suspected. The most common laboratory
      findings associated with a seizure are abnormal sodium and glucose levels.
      Patients with a normal neurologic examination, normal test results, and no
      structural brain disease do not require hospitalization or antiepileptic
      medications. Treatment with antiepileptic medications reduces the one- to two
      year risk of recurrent seizures but does not reduce the long-term risk of
      recurrence and does not affect remission rates. Regardless of etiology, a seizure
      diagnosis severely limits a patient's driving privileges, although laws vary by
      state.

PMID- 17508529
TI  - Information from your family doctor. Seizures: what you should know.

PMID- 17508530
TI  - Universal newborn hearing screening.
AB  - Congenital hearing loss is estimated to affect one in every 1,000 newborns.
      Causes of hearing loss can be conductive, sensorineural, mixed, or central. Known
      risk factors for congenital hearing loss include cytomegalovirus infection and
      premature birth necessitating a stay in the neonatal intensive care unit.
      However, up to 42 percent of profoundly hearing-impaired children will be missed
      using only risk-based screening. Universal newborn hearing screening is a way to
      identify hearing-impaired newborns with or without risk factors. Newborns with
      positive screening tests should be referred for definitive testing and
      intervention services. Whether early intervention in hearing-impaired children
      identified with universal screening improves language and communication skills
      has not been established by good-quality studies. However, universal screening
      has been endorsed by most national children's health organizations because of the
      ease of administering the screening tests and the ability to identify children
      who may need early intervention.

PMID- 17508531
TI  - Pleurisy.
AB  - Pleuritic chest pain is a common presenting symptom and has many causes, which
      range from life-threatening to benign, self-limited conditions. Pulmonary
      embolism is the most common potentially life-threatening cause, found in 5 to 20
      percent of patients who present to the emergency department with pleuritic pain.
      Other clinically significant conditions that may cause pleuritic pain include
      pericarditis, pneumonia, myocardial infarction, and pneumothorax. Patients should
      be evaluated appropriately for these conditions before an alternative diagnosis
      is made. History, physical examination, and chest radiography are recommended for
      all patients with pleuritic chest pain. Electrocardiography is helpful,
      especially if there is clinical suspicion of myocardial infarction, pulmonary
      embolism, or pericarditis. When these other significant causes of pleuritic pain
      have been excluded, the diagnosis of pleurisy can be made. There are numerous
      causes of pleurisy, with viral pleurisy among the most common. Other etiologies
      may be evaluated through additional diagnostic testing in selected patients.
      Treatment of pleurisy typically consists of pain management with nonsteroidal
      anti-inflammatory drugs, as well as specific treatments targeted at the
      underlying cause.

PMID- 17508532
TI  - Management of hypertriglyceridemia.
AB  - Hypertriglyceridemia is associated with an increased risk of cardiovascular
      events and acute pancreatitis. Along with lowering low-density lipoprotein
      cholesterol levels and raising high-density lipoprotein cholesterol levels,
      lowering triglyceride levels in high-risk patients (e.g., those with
      cardiovascular disease or diabetes) has been associated with decreased
      cardiovascular morbidity and mortality. Although the management of mixed
      dyslipidemia is controversial, treatment should focus primarily on lowering low
      density lipoprotein cholesterol levels. Secondary goals should include lowering
      non-high-density lipoprotein cholesterol levels (calculated by subtracting high
      density lipoprotein cholesterol from total cholesterol). If serum triglyceride
      levels are high, lowering these levels can be effective at reaching non-high
      density lipoprotein cholesterol goals. Initially, patients with
      hypertriglyceridemia should be counseled about therapeutic lifestyle changes
      (e.g., healthy diet, regular exercise, tobacco-use cessation). Patients also
      should be screened for metabolic syndrome and other acquired or secondary causes.
      Patients with borderline-high serum triglyceride levels (i.e., 150 to 199 mg per
      dL [1.70 to 2.25 mmol per L]) and high serum triglyceride levels (i.e., 200 to
      499 mg per dL [2.26 to 5.64 mmol per L]) require an overall cardiac risk
      assessment. Treatment of very high triglyceride levels (i.e., 500 mg per dL [5.65
      mmol per L] or higher) is aimed at reducing the risk of acute pancreatitis.
      Statins, fibrates, niacin, and fish oil (alone or in various combinations) are
      effective when pharmacotherapy is indicated.

PMID- 17508533
TI  - Information from your family doctor. Hypertriglyceridemia: what you should know.

PMID- 17508535
TI  - Swelling of the right ear.

PMID- 17508536
TI  - How do EHRs affect the physician-patient relationship?

PMID- 17508537
TI  - [Progress and problems in the treatment of cardiac arrhythmias in patients with
      heart failure].

PMID- 17508538
TI  - [Myocardial regenerative medicine for heart failure--the present situation and
      prospects in the future].

PMID- 17508539
TI  - [Epidemiology of heart failure in Japan].

PMID- 17508540
TI  - [Epidemiology of heart failure in western countries].

PMID- 17508541
TI  - [50-year trends in the incidence and prognosis of heart failure: the Framingham
      study].

PMID- 17508542
TI  - [Cohort study in Europe and America].

PMID- 17508543
TI  - [Changes of natural history in Japanese patients with heart failure].

PMID- 17508544
TI  - [SERCA2a (SR Ca(2+)-ATPase)].

PMID- 17508545
TI  - [Ryanodine receptor].

PMID- 17508546
TI  - [FK506 binding protein (FKBP12/12.6)].

PMID- 17508547
TI  - [Na+/Ca2" exchanger (NCX)].

PMID- 17508548
TI  - [Microtubule cytoskeleton].

PMID- 17508549
TI  - [Modification of contractile proteins in heart failure].

PMID- 17508550
TI  - [Myocardial dystrophin and its related proteins].

PMID- 17508551
TI  - [AT1 receptor and AT2 receptor].

PMID- 17508552
TI  - [Aldosterone].

PMID- 17508553
TI  - [Cardioprotective effects of natriuretic peptides].

PMID- 17508554
TI  - [Adrenomedullin].

PMID- 17508555
TI  - [Endothelin].

PMID- 17508556
TI  - [Ghrelin].

PMID- 17508557
TI  - [Adipocytokine].

PMID- 17508558
TI  - [KLF5].

PMID- 17508559
TI  - [The role of tenascin C in the development of myocardial remodeling].

PMID- 17508560
TI  - [ROS and disorder of mitochondrial DNA].

PMID- 17508561
TI  - [Role of oxidative stress in angiotensin II-induced heart failure].

PMID- 17508562
TI  - [Mechanisms of increased sympathetic nerve activity in heart failure].

PMID- 17508563
TI  - [A change of signal transmission from sympathetic nervous system receptor
      (adrenergic receptor)].

PMID- 17508564
TI  - [Mutations in sarcomere protein genes as a cause of heart failure].

PMID- 17508565
TI  - [Cardiac fibrosis].

PMID- 17508566
TI  - [The systolic and diastolic dysfunction].

PMID- 17508567
TI  - [Cardiac remodeling].

PMID- 17508568
TI  - [The pathophysiology of refractory cardiac failure].

PMID- 17508569
TI  - [Systolic heart failure and diastolic heart failure].

PMID- 17508570
TI  - [Electrocardiogram].

PMID- 17508572
TI  - [Cardiac catheterization].

PMID- 17508571
TI  - [Echocardiography, Doppler echocardiography].

PMID- 17508573
TI  - [Myocardial scintigraphy and positron emission tomography].

PMID- 17508574
TI  - [Cardiac CT and MRI].

PMID- 17508575
TI  - [Nuclear cardiology: PET, SPECT].

PMID- 17508576
TI  - [Plasma brain natriuretic peptide as a useful biomarker of heart failure].

PMID- 17508578
TI  - [MMPs].

PMID- 17508577
TI  - [Development of rapid BNP assay systems].

PMID- 17508579
TI  - [Genetic testing].

PMID- 17508580
TI  - [Bedside rapid measuring instrument--PATHFAST].

PMID- 17508581
TI  - [The points of differential diagnosis for heart failure].

PMID- 17508582
TI  - [ACC/AHA 2005 guideline].

PMID- 17508583
TI  - [Japanese Circulation Society Guideline for the evaluation and management of
      chronic heart failure].

PMID- 17508584
TI  - [J-DHF Study (Japanese Diastolic Heart Failure Study)].

PMID- 17508585
TI  - [Candesartan in heart failure: assessment of reduction in mortality and
      morbidity].

PMID- 17508586
TI  - [MUCHA(Multicenter Carvedilol Heart Failure Dose Assessment Trial)].

PMID- 17508587
TI  - [J-CHF Study].

PMID- 17508588
TI  - [Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival
      Study].

PMID- 17508589
TI  - [The clinical usefulness of diuretics for chronic heart failure in ALLHAT].

PMID- 17508590
TI  - Talk is cheap, Prime Minister--fix aged care Now!

PMID- 17508591
TI  - Criminal history checks--know your rights.

PMID- 17508592
TI  - Refusal of treatment--an absolute right of the patient or client.

PMID- 17508593
TI  - Introducing managerialism.

PMID- 17508594
TI  - What you should know about the Australian Health Care Agreement.

PMID- 17508595
TI  - Private hospital nurses under attack. A nurse's guide to employment in private
      hospitals in Queensland in 2007.

PMID- 17508596
TI  - Thirty year celebration of journal publications on radiation oncology medical
      physics.
AB  - The Australasian Physical & Engineering Sciences in Medicine Journal (APESM) is
      an avenue for the profession to report scientific work in medicine; provide a
      facility for the publication of current work, new research and new techniques
      developed or reviewed; report on professional news from elsewhere and; publish
      the Australasian College of Physical Scientists and Engineers in Medicine
      (ACPSEM) policies and protocols. The journal is a vital instrument within the
      ACPSEM organisation with a worldwide circulation. This review of APESM on medical
      physics in radiation oncology is meant to be a progress summary of work in that
      specialty. Even so, it has become a lengthy appraisal due to the many years
      involved. In considering publications related to medical physics in radiation
      oncology, this review has shown the progression of the College journal to an
      international journal. There is an increase in the number of papers contributed
      from Asia and other countries world wide for this discipline. Growth in the
      number of contributions should continue to rise. In order to provide some
      appreciation of where the present medical physics activity arose from, this
      article commences its discussion in 1959 and progresses towards the present,
      describing along the way, from radiation oncology papers published in APESM, the
      use of linear accelerators, brachytherapy, the medical physics workforce, the
      formation of the ACPSEM, and the more modern developments in radiotherapy such as
      3-D treatment planning and IMRT.

PMID- 17508597
TI  - A survey of the Australasian clinical medical physics and biomedical engineering
      workforce.
AB  - A survey of the medical physics and biomedical engineering workforce was carried
      out in 2006. 495 positions (equivalent to 478 equivalent full time (EFT)
      positions) were captured by the survey. Of these 268 EFT were in radiation
      oncology physics, 36 EFT were in radiology physics, 44 were in nuclear medicine
      physics, 101 EFT were in biomedical engineering and 29 EFT were attributed to
      other activities. The survey reviewed the experience profile, the salary levels
      and the number of vacant positions in the workforce for the different disciplines
      in each Australian state and in New Zealand. Analysis of the data identifies
      staffing shortfalls in the various disciplines and demonstrates the difficulties
      that will occur in trying to train sufficient physicists to raise staffing to an
      acceptable level.

PMID- 17508598
TI  - Intensity modulated radiotherapy dosimetry with ion chambers, TLD, MOSFET and
      EDR2 film.
AB  - Purpose of this study was to report in a together our experience of using ion
      chambers, TLD, MOSFET and EDR2 film for dosimetric verification of IMRT plans
      delivered with dynamic multileaf collimator (DMLC). Two ion chambers (0.6 and
      0.13 CC) were used. All measurements were performed with a 6MV photon beam on a
      Varian Clinac 6EX LINAC equipped with a Millennium MLC. All measurements were
      additionally carried out with (LiF:Mg,TI) TLD chips. Five MOSFET detectors were
      also irradiated. EDR2 films were used to measure coronal planar dose for 10
      patients. Measurements were carried out simultaneously for cumulative fields at
      central axis and at off-axis at isocenter plane (+/- 1, and +/- 2 cm). The mean
      percentage variation between measured cumulative central axis dose with 0.6 cc
      ion chamber and calculated dose with TPS was -1.4% (SD 3.2). The mean percentage
      variation between measured cumulative absolute central axis dose with 0.13 cc ion
      chamber and calculated dose with TPS was -0.6% (SD 1.9). The mean percentage
      variation between measured central axis dose with TLD and calculated dose with
      TPS was -1.8% (SD 2.9). A variation of less than 5% was found between measured
      off-axis doses with TLD and calculated dose with TPS. For all the cases, MOSFET
      agreed within +/- 5%. A good agreement was found between measured and calculated
      isodoses. Both ion chambers (0.6 CC and 0.13 CC) were found in good agreement
      with calculated dose with TPS.

PMID- 17508599
TI  - Calculation of dose profiles in stereotactic synchrotron microplanar beam
      radiotherapy in a tissue-lung phantom.
AB  - Synchrotron x-ray beams with high fluence rate and highly collimated may be used
      in stereotactic radiotherapy of lung tumours. A bundle of converging
      monochromatic x-ray beams having uniform microscopic thickness i.e. (microplanar
      beams) are directed to the center of the tumour, delivering lethal dose to the
      target volume while sparing normal cells. The proposed technique takes advantage
      of the hypothesised repair mechanism of capillary cells between alternate
      microbeam zones, which regenerate the lethally irradiated endothelial cells. The
      sharply dropping lateral dose of a microbeam provides low scattered dose to the
      off-target interbeam volume. In the target volume the converging bundle of beams
      are closely spaced, and relatively high primary and secondary electron doses
      overlap and produce a high dose region between the beams. This higher and lower
      dose margins in the target volume allows precise targeting. The advantages of
      stereotactic microbeam radiotherapy will be lost as the dose between microbeams
      exceeds the tolerance dose of the dose limiting tissues. Therefore, it is
      essential to optimize the interbeam doses in off-target volume. The lateral and
      depth doses of 100 keV microplanar beams are investigated for a single beam and
      an array of converging microplanar beams in a tissue, lung and tissue-lung
      phantoms. The EGS5 Monte Carlo code is used to calculate dose profiles at
      different depths and bundles of beams. The maximum dose on the beam axis (peak)
      and the minimum interbeam dose (valley) are compared at different energies,
      depths, bundle sizes, heights, widths and beam spacings. The interbeam dose is
      calculated at different depths and an isodose map of the phantom is obtained. An
      acceptable energy region is found for tissue and lung microbeam radiotherapy and
      a stereotactic microbeam radiotherapy model is proposed for a 4 cm diameter and 1
      cm thick tumour on the lung phantom.

PMID- 17508600
TI  - A study on contralateral breast surface dose for various tangential field
      techniques and the impact of set-up error on this dose.
AB  - The risk of inducing contralateral breast (CLB) cancer in patients undergoing
      tangential field irradiation for the treatment of breast cancer is a serious
      concern in radiation oncology. A bilateral breast phantom made of wax attached
      onto the Alderson Rando phantom was used for studying the CLB dose for techniques
      using physical wedges, EDWs, IMRT and open fields. The skin dose to the CLB was
      measured at four different points (3 cm from the medial border of the tangential
      field (P1), nipple (P3), axilla (P4), midpoint between P3 and P1 (P2)). The
      highest measured dose occurred at P1 with the 60 degrees physical wedges; it was
      15.3% of the dose at isocentre. Similarly, the dose measured at P3 (nipple) with
      60 degrees physical wedges was 1.90 times higher than the dose with 60 degrees
      EDWs. The dose at P1 for IMRT (7.8%) was almost the same as that for the open
      field (8.7%). The skin dose measured at the nipple was 2.1 - 10.9 % of the
      isocentre dose. The highest CLB doses were contributed by medial wedged fields.
      The dose to the CLB can be reduced by using IMRT or avoiding wedging the medial
      tangential fields. A set-up error in the longitudinal direction has little impact
      on the CLB dose. Set-up errors > 1 cm in the vertical and lateral directions have
      significant impact on the CLB dose.

PMID- 17508601
TI  - Extrapolated surface dose measurements using a NdFeB magnetic deflector for 6 MV
      x-ray beams.
AB  - Extrapolated surface dose measurements have been performed using radiographic
      film to measure 2-Dimensional maps of skin and surface dose with and without a
      magnetic deflector device aimed at reducing surface dose. Experiments are also
      performed using an Attix parallel plate ionisation chamber for comparison to
      radiographic film extrapolation surface dose analysis. Extrapolated percentage
      surface dose assessments from radiographic film at the central axis of a 6 MV x
      ray beam with magnetic deflector for field size 10 x 10 cm2, 15 x 15 cm2 and 20 x
      20 cm2 are 9 +/- 3%, 13 +/- 3% and 16 +/- 3%, these compared to 14 +/- 3%, 19 +/-
      3%, and 27 +/- 3% for open fields, respectively. Results from Attix chamber for
      the same field size are 12 +/- 1%, 15 +/- 1% and 18 +/- 1%, these compared to 16
      +/- 1%, 21 +/- 1% and 27 +/- 1% for open fields, respectively. Results are also
      shown for profiles measured in-plane and cross-plane to the magnetic deflector
      and compared to open field data. Results have shown that the surface dose is
      reduced at all sites within the treatment field with larger reductions seen on
      one side of the field due to the sweeping nature of the designed magnetic field.
      Radiographic film extrapolation provides an advanced surface dose assessment and
      has matched well with Attix chamber results. Film measurement allows for easy 2
      dimensional dose assessments.

PMID- 17508602
TI  - [The stages of formation and perspectives of development of the complete-chart
      system of the medical service supply in the Armed Forces].
AB  - For a long period of existence the medical service equipment table system (ETS)
      in RF Armed Forces has proved its significance in organization of support of
      troops and naval forces with medical property during the wartime. However the
      modern opinion concerning the character of the armed struggle, organization and
      tactics of army and navy medical service require the scientifically substantiated
      revision of ETS. It is necessary for bringing the contents of first-aid boxes,
      bags and medical kits into line with the problems standing before the stages of
      medical evacuation during rendering medical care to the wounded and patients. The
      analysis of use of medical kits (first-aid boxes, bags) available in the federal
      troop concentrations, units, subunits in "hot" foci has proved the urgency of
      problem connected with ETS further improvement and its optimal solution in
      accordance with the level of military medicine development.

PMID- 17508603
TI  - [Mental health of the military service age persons].

PMID- 17508604
TI  - [The perspective technologies of treatment-and-evacuation support in conditions
      of modern military conflicts].
AB  - One of the urgent directions in improvement of the system of RF AF medical
      support is the use of automation means, the final aim of which is the improvement
      of troops (forces) medical support quality under conditions of modern military
      conflicts. Robotization of medical service activities (of those aspects where it
      is possible and reasonable) will allow improving the labor productivity and
      efficiency of medical staff, reducing the risk of combat injury, protecting the
      medical service personnel from extreme factors of physical, chemical and
      biological nature.

PMID- 17508605
TI  - [About psychotropic effect of polyunsaturated fatty acid preparations belonging
      to "Omega-3" calss on the healthy person].

PMID- 17508606
TI  - [Investigation of evoked acoustic brainstem potentials in norm and pathology].

PMID- 17508607
TI  - [The types of matrimonial relations and personal characteristics of married
      couples in the families of men suffering from alcoholism].
AB  - The family of patient suffering from alcoholism was investigated form the
      standpoints of systemic analysis, that allowed revealing the leading personal
      characteristics of married couples. The men suffering from alcoholism are
      characterized by weak will, inclination to dependence, disregard of behavioral
      social norms, increased excitability and tendency to frustration in combination
      with high level of aggressiveness against the background of decreased masculine
      and prevailing feminine characteristics. Co-dependent wives of men suffering from
      alcoholism are characterized by predominance, observance of social norms,
      pronounced autoagression and orientation to masculine characteristics against the
      background of high indices of both femininity and masculinity. Such combination
      of married couples' personal characteristics forms the basis for development of
      dysfunctional relations in a family of man suffering from alcoholism. The
      families where husband and wife had no alcohol dependence, with harmonic
      functional relations served as the control group.

PMID- 17508608
TI  - [Technologies of laser prophylaxis of depressive disorder relapses].

PMID- 17508609
TI  - [The use of mesh endoprostheses in the surgical treatment of anterior ventral
      hernias].

PMID- 17508610
TI  - [Cortexin and metabolic activators in the therapy of post-abstinent syndrome].

PMID- 17508611
TI  - [About cavinton therapy of the patients with brain vascular diseases].

PMID- 17508612
TI  - [The assessment of economic loss during detection and examination of hemocontact
      virus hepatitis and HIV].

PMID- 17508613
TI  - [About prophylaxis of psychogenic disorders in servicemen].

PMID- 17508614
TI  - [Legal aspects of rendering stomatological care].

PMID- 17508615
TI  - [The N.V. Sklifosovsky Institute in the battle of Moscow (1941-1942)].

PMID- 17508616
TI  - [Historical-and-legal aspects of veterinary education and award of medical and
      veterinary scientific degrees in Russia].

PMID- 17508617
TI  - [Changes in intracellular calcium dynamics observed during the development of
      alcohol psychological and physical dependence].

PMID- 17508618
TI  - [Effects of ethanol on the development of circadian time keeping system].
AB  - Ethanol exposure during gestation can have devastating consequences on the
      developing organism. Children who have a history of prenatally exposure to
      ethanol may show morphological and functional alterations, referred to as fetal
      alcohol spectrum disorders (FASD). Fetal alcohol syndrome (FAS), which is
      characterized by pre- and postnatal growth deficiency, specific cranial/facial
      features, and dysfunction of central nervous system, is the most severe end of
      FASD. FAS or FASD children are known to suffer from disturbance of sleep and/or
      food intake behaviors. These neuropsychiatric symptoms may be due to impairment
      of the system regulating circadian rhythms. Recently, animal studies revealed
      that ethanol exposure during brain development can cause alterations in the
      circadian rhythm and its regulating system. We examined the effects of pre- or
      postnatal exposure to ethanol on the circadian rhythm in adulthood by measuring
      deep body temperature and wheel running activity in rats. After a phase delay in
      the light/dark cycle, ethanol-exposed rats took longer than control rats to
      resynchronize to the new light/dark cycle. These results suggest that both pre-
      and postnatal ethanol exposure impair the development of the circadian clock
      response to light cue. Because abnormal development of the circadian clock system
      might contribute to the neuropsychiatric symptoms seen in FASD, it is believed
      that normalizing the disturbed rhythm improves the symptoms. However, the
      mechanisms of dysfunction and potential interventions for disturbance of
      circadian clock system still remain to be elucidated. Further investigations are
      required to fully understand long-term effects of ethanol on the development of
      circadian rhythms.

PMID- 17508619
TI  - [Organic solvent psychosis--report of two cases utilizing day care treatment].

PMID- 17508620
TI  - The dimensional accuracy of four impression techniques with the use of addition
      silicone impression materials.
AB  - OBJECTIVE: The aim of this study was to assess the influence of impression
      technique selection on the dimensional accuracy of the produced casts.
      METHODOLOGY: Four impression techniques (single-stage, two-stage, monophase, and
      heavy/wash technique) were used to make addition silicone impressions of a
      phantom head maxillary jaw. The impression materials used were Aquasil, Extrude,
      and Imprint. Measurements on casts were made for the inter-abutment distances to
      assess dimensional accuracy. RESULTS: There was a significant difference (p <
      0.05) for the anteroposterior distances with the single-stage technique. The
      crossarch distances were slightly increased compared with the master model for
      all techniques, but significant statistical differences were only recorded for
      the single-stage technique and the monophase technique. The monophase technique
      demonstrated irregular results. The heavy/wash technique showed no significant
      differences for all the measurements compared with the standard model.
      CONCLUSION: The results suggest that the selection of impression technique is an
      important factor that can affect the dimensional accuracy of the subsequent
      models which are used for indirect restorations.

PMID- 17508621
TI  - Treatment of periodontal disease by photodisinfection compared to scaling and
      root planing.
AB  - OBJECTIVE: The aim of the present study was to compare the effectiveness of a
      photodisinfection process to that of scaling and root planing (SRP) for non
      surgical periodontal treatment. METHODOLOGY: Thirty-three subjects with moderate
      to advanced periodontal disease were randomly treated in one of three study arms
      with either photodisinfection (PD) alone (Group 1) using a diode laser and
      photosensitizer combination, with SRP alone (Group 2), or with SRP and PD
      combined (Group 3). Clinical assessments of bleeding on probing (BOP), probing
      pocket depth (PPD), and clinical attachment level (CAL) were made at baseline,
      three weeks, six weeks, and 12 weeks following therapy. RESULTS: No difference in
      any of the investigated parameters was observed at baseline between the three
      groups. The mean value of BOP decreased in the PD group (Group 1) from baseline
      by 71% at six weeks and 73% at 12 weeks, and in the SRP alone group (Group 2)
      from baseline by 43% at six weeks and 56% at 12 weeks. The BOP in the combined
      SRP + PD group (Group 3) decreased from baseline by 65% at six and 59% at 12
      weeks. The sites treated with PD alone demonstrated mean CAL gains of 0.09 +/-
      0.38 mm and 0.14 +/- 0.65 mm at six and 12 weeks, respectively. Those sites
      treated with SRP alone demonstrated mean CAL gains of 0.37 +/- 0.34 mm and of
      0.36 +/- 0.35 mm at six and 12 weeks, respectively. The final group of SRP + PD
      demonstrated mean CAL gains of 0.92 +/- 0.62 mm and 0.86 +/- 0.61 mm at six and
      12 weeks, respectively (p < 0.01 for six weeks and p < 0.02 for 12 weeks when
      compared to SRP alone). The sites treated with PD alone demonstrated mean PPD
      reductions of 0.69 +/- 0.33 mm and of 0.67 +/- 0.44 mm at six and 12 weeks,
      respectively. Those sites treated with SRP alone demonstrated mean PPD reductions
      of 0.78 +/- 0.47 mm and 0.74 +/- 0.43 mm at six and 12 weeks, respectively. The
      final group of SRP + PD demonstrated mean PPD reductions of 1.16 +/- 0.39 mm and
      1.11 +/- 0.53 at six and 12 weeks, respectively (p < 0.06 for six weeks and p <
      0.05 for 12 weeks when compared to SRP alone). CONCLUSION: Within the limits of
      the present study, it can be concluded that SRP combined with photodisinfection
      leads to significant improvements of the investigated parameters over the use of
      SRP alone.

PMID- 17508622
TI  - Statistical modeling of dental unit water bacterial test kit performance.
AB  - OBJECTIVE: While it is important to monitor dental water quality, it is unclear
      whether in-office test kits provide bacterial counts comparable to the gold
      standard method (R2A). Studies were conducted on specimens with known bacterial
      concentrations, and from dental units, to evaluate test kit accuracy across a
      range of bacterial types and loads. METHODOLOGY: Colony forming units (CFU) were
      counted for samples from each source, using R2A and two types of test kits, and
      conformity to Poisson distribution expectations was evaluated. Poisson regression
      was used to test for effects of source and device, and to estimate rate ratios
      for kits relative to R2A. RESULTS: For all devices, distributions were Poisson
      for low CFU/mL when only beige-pigmented bacteria were considered. For higher
      counts, R2A remained Poisson, but kits exhibited over-dispersion. Both kits
      undercounted relative to R2A, but the degree of undercounting was reasonably
      stable. Kits did not grow pink-pigmented bacteria from dental-unit water
      identified as Methylobacterium rhodesianum. CONCLUSION: Only one of the test kits
      provided results with adequate reliability at higher bacterial concentrations.
      Undercount bias could be estimated for this device and used to adjust test kit
      results. Insensitivity to methylobacteria spp. is problematic.

PMID- 17508623
TI  - Evaluation of the safety and efficacy of an automated flossing device: a
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a newly developed automated
      flossing device (AF). METHODOLOGY: Subjects were recruited from a university
      campus via announcements, and were randomly assigned to a control (C), manual
      (M), or automated (A) group. Subjects brushed twice a day and treatment groups
      used their respective floss daily. The safety assessment (SA), plaque index (PI),
      and gingival index (GI) were measured at days one, 15, and 30. A pre- and post
      intervention PI was measured at days 15 and 30. RESULTS: The majority of subjects
      (n=76) were students, mean age +/- SD of 23.3 +/- 5.2 years. Based on one-way
      analysis of covariance, C had a higher mean PI score than A at days 15 (p =
      0.019) and 30 (p < 0.001), and M had a higher mean PI score than A at day 30 (p =
      0.022). The C had a higher mean GI score than A at day 30 (p = 0.034). The SA
      included trauma associated with improper use of the AF for two subjects.
      CONCLUSION: At four weeks, the AF removed more interproximal plaque than M, and
      there was less interdental inflammation compared to brushing alone. The AF is
      safe and effective when used properly, and demonstrates great promise as an
      alternative to manual floss.

PMID- 17508624
TI  - Plaque removal efficacy of a novel manual toothbrush with MicroPulse bristles and
      an advanced split-head design.
AB  - OBJECTIVE: To assess the plaque removing efficacy and safety of a novel manual
      toothbrush (Oral-B Pulsar-PUL) compared to leading manual and battery
      toothbrushes. METHODOLOGY: Three clinical studies were conducted, each having a
      randomized, examiner-blind, crossover design. Study 1 compared PUL to a newly
      marketed manual toothbrush, Colgate 360 degrees (COL), Study 2 compared PUL to
      the Oral-B Advantage Plus (AP) and Oral-B CrossAction (CA) manual toothbrushes,
      and Study 3 compared PUL to two battery toothbrushes, Oral-B CrossAction Power
      (CAP) and Crest SpinBrush Pro (SBP). Before each brushing visit, subjects
      refrained from all oral hygiene procedures for 23-25 hours, received an oral
      tissue examination, and pre-brushing plaque was scored based on the Rustogi et.
      al, odified Navy Plaque Index. After subjects brushed with the assigned
      toothbrush in their usual manner for one minute, oral tissues were then re
      examined and post-brushing plaque scores recorded. Subjects with pre-brushing
      whole mouth mean plaque scores > or = 0.6 continued in the study after the first
      visit. Following a brief washout period between additional visits, the above
      procedures were repeated in the remaining treatment periods. The examiners who
      made all clinical measurements were blinded to the treatment sequence. RESULTS:
      All toothbrushes significantly (p = 0.0001) reduced plaque levels from all areas
      after a single brushing. Study 1 showed a significant difference for PUL in all
      areas, whole mouth, margin, and approximal (p < 0.05) compared to COL. In Study
      2, PUL removed significantly more whole mouth (p < 0.01) and approximal plaque (p
      < 0.005) than AP as scored by two examiners, but did not show a significant
      advantage versus CA. In Study 3, PUL removed significantly more plaque than CAP
      and SBP for whole mouth (both p = 0.0001), marginal (both p = 0.0001), and
      approximal (p < 0.005, p = 0.0001, respectively) areas. All toothbrushes were
      found to be safe with no evidence of hard or soft tissue trauma. CONCLUSION: The
      new Oral-B Pulsar toothbrush removed significantly more plaque than Colgate 360
      and Oral-B Advantage Plus. Additionally, Pulsar removed significantly more plaque
      than two battery brushes, Oral-B CrossAction Power and Crest SpinBrush Pro.

PMID- 17508626
TI  - The National Heart, Lung, and Blood Institute considers the cardiac and sleep
      consequences of temporomandibular disorders.

PMID- 17508625
TI  - Stannous fluoride/sodium hexametaphosphate dentifrice increases dentin resistance
      to tubule exposure in vitro.
AB  - OBJECTIVE: The purpose of this study was to compare the reactivity of three
      dentifrice formulations on smear layer-covered root dentin surfaces, and the
      effects of the formulation treatments on resistance to acid softening and
      dentinal tubuli disclosure. METHODOLOGY: Commercial dentifrices, including Crest
      Cavity Protection Regular, Colgate Total, and a new dentifrice comprised of
      stannous fluoride/sodium hexametaphosphate (SnF2/HMP: Crest Pro-Health), were
      cycled through a pre-treatment period on smear layer-covered dentin surfaces,
      including intermittent soaking in dentifrice slurries and whole human saliva
      immersion. Following pre-treatments, the cycling treatments were modified to
      include dietary acid exposure, including soaks in an acidic soft drink. Vickers
      surface microhardness, variable pressure scanning electron microscopy (VP-SEM),
      and confocal laser scanning microscopy in reflection mode (CLSM) were used to
      characterize dentin reactivity and smear layer protection. RESULTS: CLSM and SEM
      analyses showed that specimens treated with SnF2/HMP appeared to resist acid
      solubilization, evidenced by the absence of disclosed dentinal tubuli. The histo
      tomographic observations in this study were in agreement with the hardness
      measurements. The superior surface protection of dentin with SnF2/HMP would
      suggest potential benefits in ameliorating dentinal hypersensitivity in the
      clinical situation. CONCLUSION: A stannous fluoride/sodium hexametaphosphate
      dentifrice prevents dietary acid softening and tubule exposure of smear layer
      dentin surfaces.

PMID- 17508627
TI  - Are you perceived as an expert? Says who?

PMID- 17508628
TI  - Evaluation of the posterior airway space following Biobloc therapy: geometric
      morphometrics.
AB  - The aim of this study was to evaluate changes in the posterior airway space in
      patients following Biobloc therapy, using geometric morphometrics. Pre- and post
      treatment lateral cephalographs of 53 children (mean age, 12.9 +/- 1.5 years;
      mean treatment time, 21.3 +/- 6.2 months) were scanned and 27 landmarks
      encompassing the airway were digitized. Mean configurations were computed using
      Procrustes superimposition, followed by principal components analysis (PCA) and
      finite-element scaling analysis (FESA). Marked shape-changes were identified
      using PCA for the airway following treatment (p < 0.01). Using pseudo-colored
      FESA, a relative 31% increase in nasopharyngeal airway area was found above and
      behind the soft palate. Additionally, a 23% increase in oropharyngeal airway area
      was located behind the base of the tongue with a 9% increase in hypopharyngeal
      area near the level of the hyoid bone. Functional airway improvements are
      associated with Biobloc treatment in actively growing patients.

PMID- 17508629
TI  - Correlations between incisor and condyle motion during protrusion in children
      with primary dentition.
AB  - The purpose of this study was to investigate the relationship between incisor and
      condyle movement during protrusion in children with primary dentition. Subjects
      were categorized into two age groups. A primary dentition group consisted of 20
      children, and a permanent dentition group consisted of 25 women. The occlusion
      and TMJ in both groups were normal, with no history of orthodontic treatment.
      Three orthogonal excursive ranges, linear distance and curvilinear distance of
      the incisal and condylar points; sagittal angle of condylar rotation; and
      correlations between incisor and condyle distances during protrusion were
      estimated by using multilevel statistical models. Protrusion in children with
      primary dentition was characterized by: 1. significantly smaller superior
      inferior ranges for incisal and condylar points in children than in adults; 2.
      strong positive correlations between incisor and condylar anterior-posterior
      ranges and linear distances, a pattern similar to that in adults.

PMID- 17508630
TI  - The association between posture of the head and malocclusion in Saudi subjects.
AB  - The purpose of the present study was to examine whether a relationship exists
      between posture of the head and neck, and the presence of certain malocclusal
      problems. Dental models, in addition to lateral cephalometric radiographs, taken
      in the "natural head position" of 180 male and female subjects were obtained. The
      postural angles between the head and the cervical column, termed craniovertical,
      craniocervical, cervicohorizontal, and cervical curvature, were measured. The
      malocclusal traits studied were: molar relation, crowding, spaces, overbite,
      overjet, crossbites, and midline displacements. Results show that a relationship
      between crowding and head posture could only be found in subjects with upper arch
      crowding and cervical curvature (p<0.01). A significant difference in
      craniocervical and cervicohorizontal angles was observed in subjects with
      overbite, compared to subjects without overbite (p<0.01, p<0.001). The influence
      of gender on overbite and head posture was also found to be strongly correlated
      (p<0.05). With regard to molar relation, Class II malocclusion showed a stronger
      relation with craniovertical and cervicohorizontal angles than both other classes
      (p<0.05, p<0.01). A significant correlation was found between craniovertical
      angles NSL/VER and overjet, irrespective of gender or age (p<0.05). Crossbite was
      strongly correlated with all craniocervical angles (p<0.05). It can be concluded
      that certain malocclusal problems are more strongly associated with head posture
      than others, and that crowding does not seem to play a major role in this
      association in the present study.

PMID- 17508631
TI  - Laterotrusive occlusal schemes and jaw posture tasks effects on supra- and
      infrahyoid EMG activity in the lateral decubitus position.
AB  - The purpose of this study was to determine the effect of canine guidance and
      group function on supra- and infrahyoid EMG activity in the lateral decubitus
      position at different jaw posture tasks. The sample included 40 healthy subjects
      with natural dentition and bilateral molar support, 20 with bilateral canine
      guidance and 20 with bilateral group function. An inclusion criterion was that
      subjects had to be free of signs and symptoms of any dysfunction of the
      masticatory system. Bipolar surface electrodes were located on the left supra-
      and infrahyoid muscles for EMG recordings. In the lateral decubitus position, EMG
      activity was recorded in subjects with canine guidance or group function, during
      the following jaw posture tasks: A. maximal clenching in the edge-to edge lateral
      contact position; B. grinding from intercuspal position to edge-to-edge lateral
      contact position, and C. grinding from edge-to-edge lateral contact position to
      intercuspal position. Supra- and infrahyoid EMG activity was not significantly
      different with canine guidance or group function (mixed model with unstructured
      covariance matrix). Overall comparison of suprahyoid or infrahyoid EMG activity
      among the three jaw posture tasks studied showed a significantly higher activity
      during jaw posture task A (clenching) than jaw posture tasks B and C (grinding).
      Suprahyoid EMG activity was significantly higher during jaw posture task C than
      B, whereas infrahyoid EMG activity did not present a significant difference
      between jaw posture tasks C and B. These EMG patterns observed could be of
      clinical importance in the presence of parafunctional habits, i.e., clenching
      and/or grinding. The neurophysiological mechanisms involved are discussed.

PMID- 17508632
TI  - Examination of a large patient population for the presence of symptoms and signs
      of temporomandibular disorders.
AB  - Temporomandibular Disorder (TMD) is a term generally applied to a condition or
      conditions characterized by pain and/or dysfunction of the masticatory apparatus.
      Its characterization has been difficult because of the large number of symptoms
      and signs attributed to this disorder and to variation in the number and types
      manifested in any particular patient. For this study, data on 4,528 patients,
      presenting over a period of 25 years to a single examiner for TMD treatment, was
      made available for retrospective analysis and determination of whether the TMD
      care-seeking patient can be profiled, particularly pain difficulties. All
      patients in this database filled out a questionnaire and were examined for the
      prevalence of a range of symptoms and clinical examination findings (signs)
      commonly attributed to TMD. There was no attempt in this study to assign patients
      to TMD diagnostic subcategories. The data collected were analyzed to determine
      which of these symptoms and signs were sufficiently "characteristic of the TMD
      condition" that they might be used in diagnosis, research and treatment,
      especially in patients needing relief from pain and discomfort. All 4,528
      patients reported symptoms and all but 190 of them also showed signs upon
      examination. Symptoms most commonly reported on the questionnaire included (i)
      pain (96.1%), (ii) headache (79.3%), (iii) temporomandibular joint discomfort or
      dysfunction (75.0%) and (iv) ear discomfort or dysfunction (82.4%). In the 4,338
      patients who showed signs, the most prevalent was tenderness to palpation of the
      pterygoid muscles (85.1%), followed by tenderness to palpation of the
      temporomandibular joints (62.4%). Pain symptoms and signs were often accompanied
      by compromised mandibular movements, TMJ sounds and dental changes, such as
      incisal edge wear and excessive overbite. Clearly prevalence of pain disclosed by
      the symptoms and signs examinations was high. Patients showed variable prevalence
      and nonprevalence of eight categories of painful symptoms and seven categories of
      painful signs. Despite the variability, these might be developed in the future
      into TMD scores or indices for studying and unraveling the TMD conundrum.

PMID- 17508633
TI  - Clinical features of the stomatognathic involvement in fibromyalgia syndrome: a
      comparison with temporomandibular disorders patients.
AB  - Several studies have reported an involvement of the stomatognathic system in the
      course of fibromyalgia (FM) similar to that which characterizes temporomandibular
      disorders (TMD). The aim of this study was to investigate and compare the
      clinical features of stomatognathic dysfunction in patients with FM and TMD.
      Ninety-three FM patients underwent an assessment according to the RDC/TMD
      guidelines. Prevalence of the different RDC/TMD diagnoses and some clinical
      parameters of FM patients were compared with those of 181 patients affected by
      TMD. Seventy-four (79.6%) FM patients presented at least one RDC/TMD diagnosis
      and showed lower mean maximum voluntary and passive mouth opening values than TMD
      patients. Moreover, 34 FM patients presented with trigger and/or tender points.
      Results of the present study confirm the high rate of involvement of the
      stomatognathic system in the course of FM and support the need for a careful
      multidisciplinary approach to patients with TMD, including the rheumatologist.

PMID- 17508635
TI  - Trigeminal nerve injury following accidental airbag deployment and assessment
      with quantitative sensory testing.
AB  - High velocity motor vehicle accidents are associated with an increase in
      mortality rates and a significant number of facial injuries. Accidental
      deployment of airbags and the associated release of hot gases can result in both
      thermal and mechanical injuries. The more commonly reported maxillofacial
      injuries include temporomandibular joint fractures and dislocations, dental
      trauma, facial nerve paralysis, and other orofacial pain complaints. The
      following case report describes a patient with facial trauma from the accidental
      deployment of an airbag resulting in complaints consistent with a neurological
      injury for which quantitative sensory testing was used in confirming the
      diagnosis.

PMID- 17508634
TI  - Traumatic fractures of the tympanic plate: a literature review and case report.
AB  - Fracture of the tympanic plate resulting from posterior dislocation of the
      mandibular condyle is an uncommon diagnosis. Presented is a clinical case in
      which computerized tomography was used as a diagnostic resource in a conservative
      therapeutic and clinical controlled one-year study. A review of the literature
      revealed 23 cases clinically reported with symptoms, diagnosis, and types of
      therapy utilized.

PMID- 17508636
TI  - Anatomic and dynamic aspects of stomatognathic structures in osteogenesis
      imperfecta: a case report.
AB  - The osteogenesis imperfecta congenita (OMIM 166210) type II phenotype can be
      caused by mutation in either the COL1A1 gene or the COL1A2 gene that encode the
      chains of type I procollagen, the major protein in bones. Patients can therefore
      present a combination of features, including multiple long bone fractures and
      deformities, growth deficiency, joint laxity, hearing loss, blue sclera, and
      dentinogenesis imperfecta. The purpose of this study is to describe a clinical
      case of this syndrome, focusing on the anatomy of the temporomandibular joint
      (TMJ) that was assessed using computed tomography (CT) method. Clinical
      examination included evaluation of mandibular dynamics and investigation of
      temporomandibular dysfunction (TMD).

PMID- 17508637
TI  - Gelatin colloids in the resuscitation of trauma.
AB  - To date, the specific role of gelatins in trauma resuscitation remains under
      investigated. Their adverse affects are well described and relate principally to
      the provocation of allergic responses whilst their influence upon haemostasis is
      relatively benign in comparison to the other colloids. However, their benefits
      are only sparsely documented and the evidence to choose one gelatin over another
      virtually non-existent. As knowledge of the microcirculatory dysfunction inherent
      in the shocked state increases, the role of the gelatins in trauma resuscitation
      is being increasing sidelined by other colloids--notably the starches. Their role
      beyond a basic resuscitation tool is now uncertain.

PMID- 17508638
TI  - Damage control surgery and casualty evacuation: techniques for surgeons, lessons
      for military medical planners.
AB  - Damage Control Surgery (DCS) is a three-phase team-based approach to maximal
      injury penetrating abdominal trauma. In Phase I, the hypothermic, coagulopathic,
      acidotic, hypotensive casualty undergoes a proactively planned one-hour time
      limited laparotomy by an appropriately trained surgical trauma team. In phase II
      physiological stabilization takes place in the Intensive Care Unit. In phase III-
      definitive repair occurs. DCS is extremely resource intensive but will save lives
      on the battlefield. A military DCS patient will perioperatively require fourteen
      units of blood and seven units of fresh frozen plasma--half the blood stock of a
      light-scaled FST. Two DCS patients will in one day, exhaust this FSTs oxygen
      supply. We know that hypothermic patients with an iliac vascular injury (initial
      core temp < 34 degrees C) suffer four-fold increases in their mortality, yet we
      cannot heat our tents above 20 degrees C during a mild British winter. Our
      primary casualty retrieval is excessively slow. A simple casevac request has to
      go to too much 'middle-management' before a flight decision is made. In Vietnam,
      wounded soldiers arrived in hospital within twenty-five minutes of injury. In
      Iraq in 2005, that figure is over one hundred and ten minutes. We use support or
      anti-tank helicopters that are re-roled on an adhoc basis for the critical care
      and transport of our sickest patients. We still do not have a dedicated all
      weather military helicopter evacuation fleet despite significant evidence that
      intensive care unit level military evacuation is safe and eminently achievable in
      both in the primary and secondary care setting. Should we not be asking why?

PMID- 17508639
TI  - Use of ultrasound to identify chronic Achilles tendinosis in an active
      asymptomatic population.
AB  - OBJECTIVES: The aim of the study was to identify the prevalence of degenerative
      change in the Achilles tendons of currently asymptomatic individuals and
      correlate it with their degree of physical activity. METHODS: We recruited 126
      healthy subjects, mean age 33.1, range 20 - 50 (78 males and 48 females). Their
      levels of physical activity were assessed by a questionnaire and scored using the
      Allied Dunbar Fitness Survey criteria, modified to exclude non-weight bearing
      activity. One investigator, who was blinded to the activity levels, ultrasound
      scanned all 252 tendons. Tendons were examined for evidence of hypoechoic
      regions, localised fusiform thickening, and the cross-sectional diameter of each
      was measured. RESULTS: Overall 59% (149) of tendons had ultrasound evidence of
      hypoechoic regions. In 50 tendons (in 31 patients) there was a history of
      previous Achilles pain and 84% of these had hypoechoic regions. Thirty three
      percent of subjects in the lowest quartile of activity had evidence of hypoechoic
      regions compared to 72.6% in the most active quartile (Pearson Chi2 p < 0.01).
      Only 5.6% of all Achilles tendons had ultrasound evidence of localised fusiform
      thickening, with none in the inactive group compared to 6.4% in the very active
      group (Pearson Chi2 p = 0.03). CONCLUSIONS: Degenerative changes, identified by
      ultrasound, are common in the Achilles tendon and are often asymptomatic. There
      is a direct relationship between these changes and levels of current and lifetime
      activity. The natural history of asymptomatic chronic Achilles tendinosis and
      their relationship to future pain or tendon pathology is unknown.

PMID- 17508640
TI  - BATLS/BARTS training in Lithuania.
AB  - OBJECTIVE: In order to train medical personnel properly for future international
      missions the Lithuanian Armed Forces decided to adopt BATLS/BARTS as a basic
      course for military pre-hospital trauma care. This decision was based upon the
      increasing Lithuanian participation in international missions as a part of
      multinational units. Another important reason was the personal experience of the
      course concept acquired in Sweden in 2001 by five Lithuanian medical officers.
      METHODS: Similar to the way BATLS/BARTS was introduced in Sweden, a regular
      Swedish course (as given in Sweden for own units prior to international missions)
      was given in Lithuania. The faculty consisted of three experienced instructors
      from Sweden, and the two Lithuanian medical officers who had previously taken the
      BATLS course and the BATLS instructor course in Sweden. RESULTS: Two BATLS/BARTS
      courses have been given in Kaunas, Lithuania. A total number of eight medical
      officers, nine military nurses, five medics, three civilian doctors and four
      medical students have taken the course. Some of these (four medical officers, two
      military nurses and two medics) have later been deployed to Afghanistan, Iraq and
      Kosovo, where the Lithuanian units have been collaborating with British, Danish,
      Polish and Czech-Slovakian units. CONCLUSION: As international missions become
      multinational, it is essential there is full confidence in the level of training
      and preparedness among all units working together. One way to achieve this is
      through bi- or multinational training as described in this paper.

PMID- 17508641
TI  - The role of local steroid injections in an operational field hospital setting.
AB  - OBJECTIVES: To assess the safety and effectiveness of administering local steroid
      injections in an operational field hospital environment. METHOD: A prospective
      study of patients presenting to the physiotherapy department at the British
      Military Hospital (BMH) Shaibah, Iraq was undertaken from July 2006 - September
      2006. Patients with a condition amenable to local steroid injection and who had
      not improved with conservative therapy were considered for the study. They then
      underwent local injection with steroid and local anaesthetic. RESULTS: During
      this period 12 patients were identified that fitted the criteria for local
      steroid injection. This represented 7% (12/179) of patients who were seen by the
      physiotherapy department in either an in or out-patient setting. All patients
      were injected with local anaesthetic and steroid injection with a single dose of
      intravenous antibiotic as antimicrobial cover. 10/12 (83.3%) were able to return
      to their unit within this theatre of operation. The only complication was one
      case of post injection flare of pain, which settled after 48 hours. CONCLUSION:
      The use of local steroid injection, as an adjunct to physical therapy, can enable
      service personnel to remain in the theatre of operations. These patients may have
      otherwise required aero medical evacuation. We consider the use of a local
      steroid injection to be a safe and effective intervention in certain patients
      where conservative measures alone do not work. This study highlights the safety
      of using steroid injections in an operational field hospital setting. Further
      large scale studies may help corroborate this conclusion.

PMID- 17508642
TI  - Respiratory protection for Health Care Workers.
AB  - Chemical, Biological, Radiological and Nuclear incidents are rare, but the
      likelihood of any medical facility having to deal with contaminated or contagious
      casualties is not, Health Care Workers (HCW) often being exposed to infectious or
      toxic substances. Although medical staff routinely take measures to protect
      themselves against exposure to infection by wearing protective clothing, they
      rarely consider the inhalational route as a threat. This paper presents a series
      of cases where HCW's have been exposed to toxic or infectious material through
      the respiratory route, discusses standards of respiratory protection and
      describes how this risk can be mitigated to protect medical personnel.

PMID- 17508643
TI  - Attendances at a field hospital emergency department during operations in Iraq
      November 2003 to March 2004 (Operation Telic III).
AB  - OBJECTIVE: This study investigated the types of presentations; time lines and
      disposal of patients from the international, local and military community in
      Southern Iraq. METHODS: All presentations to the Emergency Department (ED) were
      clinically and demographically coded and entered onto an electronic database.
      RESULTS: During the period studied the emergency department dealt with 1455 new
      presentations of which 75% were UK Armed Forces personnel. CONCLUSIONS: This
      represented a busy period in the field hospitals time in Iraq and offered
      valuable training to emergency medicine trainees in an unusual environment.

PMID- 17508644
TI  - Posterior fracture dislocation of the hip from a Warrior turret injury.
AB  - Fracture of the femoral head after hip dislocation is a relatively rare injury
      and is often associated with a poor functional outcome. Most result from high
      impact motor vehicle accidents. We report the case of a soldier who trapped his
      foot in a traversing Warrior turret and suffered a severe abduction injury to his
      hip. He sustained a Pipkin Type I fracture-dislocation of the hip not amenable to
      closed reduction and required transfer to the American Hospital in Baghdad where
      he underwent emergency open reduction and internal fixation of the fracture. This
      case report illustrates an unusual mechanism of injury resulting in a posterior
      fracture-dislocation and reviews the literature pertaining to the presentation,
      treatment and prognosis of this condition.

PMID- 17508645
TI  - BB guns--a dangerous toy.

PMID- 17508646
TI  - Contact dermatitis after henna skin tattooing.
AB  - A case of contact dermatitis resulting from temporary tattooing with henna is
      described. The skin was stained using a dye described as 'black' henna. This is
      produced by the addition of paraphenylenediamine (PPD) to traditional henna dye
      in order to make temporary skin tattoos appear darker. Sensitisation to PPD may
      also cause sensitivity to printers' inks, clothing dyes, hair dyes, local
      anaesthetics, sulphonamides, and para-aminosalicylic acid. The case of contact
      dermatitis described responded to application of topical steroid with no
      sequelae; however patients may be left with hypo- or hyper-pigmentation of the
      skin or even permanent scarring.

PMID- 17508647
TI  - Chemical, biological, radiation and nuclear (CBRN) incidents.

PMID- 17508648
TI  - Haematology.
AB  - This article examines some of the recent advances in haematology in both the
      malignant and non-malignant areas of the speciality. Improvements in survival
      rates after effective chemotherapy now present the haematologist with the
      challenges of how to minimise therapeutic side effects without affecting outcome
      and the role of stratification as well as specific monitoring of enzyme activity
      are discussed. Many treatments for haematological malignancy have significant
      late effects which are only now becoming a problem--what these are, how to
      identify them and how they can be limited are examined. The increased knowledge
      of the altered pathways that lead to malignancy has allowed a whole slew of new
      therapies to be developed often with excellent results. The role of new iron
      chelation agents and the so called 'universal haemostatic agent' activated factor
      VII are also discussed.

PMID- 17508649
TI  - Surgery.

PMID- 17508650
TI  - LXXVII: Asthma in the British Army. 1942.

PMID- 17508651
TI  - Sir John Pringle.

PMID- 17508652
TI  - 2011 census coverage assessment and adjustment strategy.
AB  - Every effort is made to ensure everyone is counted in a census. However, no
      census is perfect and some people are missed. This underenumeration does not
      usually occur uniformly across all geographical areas or across other sub-groups
      of the population such as age and sex groups. Coverage levels in censuses across
      the world are declining leading to an increasing need to firstly slow the decline
      through improved enumeration, and secondly in improved methods and data for
      measuring coverage. In order to achieve the mission critical aims of the 2011
      Census, a coverage assessment and adjustment strategy is required. This article
      outlines the proposed strategy for the 2011 UK Census. The strategy is to
      significantly improve upon the 2001 One Number Census, and use it as a platform
      to develop an improved coverage assessment and adjustment methodology. The
      article also outlines the key areas of innovation for the 2011 strategy and the
      options that will be considered in order to develop the final strategy.
      Stakeholder management is also an important part of the strategy to ensure that
      key users both buy into and understand the methodology. ONS will look to build on
      the consultation carried out prior to the 2001 Census and widen the user base
      with which it engages on this important topic.

PMID- 17508653
TI  - Using the Omnibus Survey to test questions on emigration.
AB  - It is important that migration is measured accurately, for example to inform
      population estimates and projections. However, current sources of information
      make it difficult to produce robust estimates of emigration from Great Britain.
      Several other countries, including Ireland, make use of household surveys in
      their estimates of migration. To investigate the feasibility of obtaining
      information on emigration from those resident in Great Britain, three questions
      were included in the Omnibus Survey for two months. Respondents were asked
      whether they had plans to emigrate or whether anyone in their family had recently
      emigrated or intended to shortly. This article reports on the results of this
      pilot, providing evidence on response levels, comparison with the International
      Passenger Survey and feedback from interviewers on the questions asked.

PMID- 17508654
TI  - The feasibility of making short-term migration estimates.
AB  - Short-term migration, that is stays of less than 12 months, has received
      particular attention recently from both national and local level users of
      population statistics. This interest is part of the wider interest shown in
      increasing levels of long-term migration statistics in recent years. This article
      is an initial assessment by ONS of the potential to produce short-term migration
      estimates for England and Wales, and the challenges faced in doing so. Central to
      these challenges is the question of how short-term migration should be defined.
      In addition, illustrative estimates of short-term migration based on the
      International Passenger Survey (IPS) are provided. These illustrative estimates,
      along with associated standard errors, are provided at both national and regional
      levels using a number of definitional bases.

PMID- 17508655
TI  - 'Clocking in and out feels draconian and has the slightest edge of mistrust'.

PMID- 17508656
TI  - Why nurses need to embrace commissioning.

PMID- 17508657
TI  - Recalling the heat of combat. Interview by Clare Lomas.

PMID- 17508658
TI  - Prevention of venous thromboembolism in patients.

PMID- 17508659
TI  - Blood pressure measurement. Part one: taking a manual reading.

PMID- 17508660
TI  - Chronic obstructive pulmonary disease. Part two--management.
AB  - In the second part of this two-part series, non-drug and pharmacological
      approaches to COPD management are explored.

PMID- 17508661
TI  - [Holidays: think about vaccination!].

PMID- 17508662
TI  - [Explanation of the radiosterilization process].

PMID- 17508663
TI  - [Etology and treatment of community acquired pneumonia in children].
AB  - In children under 5 years, most lower respiratory tract infections are caused by
      viruses and do not require antibiotics. This is true for almost all episodes of
      bronchitis and bronchiolitis but also for the majority of pneumonias. Atypical
      pneumonias due to Mycoplasma pneumoniae or Chlamydia pneumoniae predominate in
      older children while Streptococcus pneumoniae remains by far the most common
      cause of bacterial pneumonia. Diagnosis of pneumonia itself can be difficult and
      relies on a combination of clinical judgement and radiological and laboratory
      investigations. In real-life situations, etiologic agents are rarely identified,
      an issue further complicated by the possibility of mixed infections particularly
      in hospitalised children. Since viruses are often the sole cause of pneumonia in
      childhood, it is appropriate not to treat every child with antibiotics. However,
      when a bacterial origin can not be excluded, antibiotics efficient on
      Streptococcus pneumoniae are to be prescribed. Amoxicillin is the first choice
      empirical antibiotic treatment, having a higher efficacy on poorly sensitive
      pneumococcus than cephalosporins. Macrolides are indicated for the treatment of
      atypical pneumonia. Current immunisation strategies have decreased the number of
      bacterial pneumonias. However, there is some evidence that among hospitalised
      children the rate of complicated pneumonias is increasing with an emerging role
      of Streptococcus pneumoniae serotype 1, which is not covered in the 7-valent
      vaccine.

PMID- 17508664
TI  - [Cystic fibrosis and pseudomonas aeruginosa current and future strategies].
AB  - Cystic fibrosis and Pseudomonas aeruginosa current and future strategies
      Pseudomonas aeruginosa is long recognized as the main pathogen in cystic fibrosis
      and avoiding or postponing chronic colonization of the lungs by this germ is
      considered as the most important challenge for the clinicians dedicated to the
      care of CF patient. The need for early intervention is widely accepted but its
      optimal modalities are still debated and the failure rate of this approach is
      estimated around 20%. This underlines the potential of other strategies including
      attempts to develop an effective vaccine against PA and anti-PA prophylaxis.
      Surprisingly enough, the latter approach which could involve early use of inhaled
      antibiotics has never been studied prospectively. In chronically colonized
      patients, inhaled antibiotics and oral azythromycin are of value, slowing the
      FEV1 decline and reducing the number of exacerbations. Whether intravenous
      antibiotics are to be used electively (during exacerbations) or more
      systematically (every 3 months for example) remains controversial.

PMID- 17508665
TI  - [Vronchiolitis and its treatment].
AB  - Bronchiolitis is the most common lower respiratory tract illness of infancy and
      is primarily caused by an infection with the respiratory syncytial virus (RSV).
      An inadequately elevated hospitalisation rate and the use of different treatments
      with unproven efficacy lead to high cost in terms of public health.
      Implementation of evidence based guidelines can reduce these costs but not
      parents satisfaction and quality of care. Palivizumab is a preventive medication
      with specific indications. Post-bronchiolitis bronchial hyperreactivity has been
      demonstrated, particularly if the first episode required hospital admission.
      However, no medication has proven its efficacy to reduce this postbronchiolitis
      hyperreactivity.

PMID- 17508666
TI  - [Prevention and treatment of asthma in child].
AB  - Asthma is a chronic inflammatory disorder of the airways with an impact on the
      life of the patient, his family and the society. Asthma is the most common
      chronic disease of the childhood. Consequently, prevention and treatment of
      asthma are real challenges in public health. Treatment includes two levels:
      prevention and medication treatment. Prevention is to avoid one or several causes
      of asthma and risk factors of exacerbations particularly in high risk population.
      Medication treatment includes the reliever treatment and the maintenance
      treatment. Bronchodilatator treatment will be used in first line treatment in
      asthma attacks. Inhaled glucocorticosteroids are the most effective controller
      medications. No treatment is curative for asthma, establishing of therapeutic
      objectives is necessary. The reliever treatment, the maintenance treatment, the
      new classification of asthma and the new recommendations of therapeutic
      management will be discussed.

PMID- 17508667
TI  - [Chest physiotherapy in the management of obstructive lung diseases in children].
AB  - Physiotherapists play a key role in the management of obstructive lung diseases
      in children. Obstructive lung diseases most frequently found are bronchiolitis,
      asthma and cystic fibrosis. The major objective of the physiotherapists, using
      various chest physiotherapy methods is the desobstruction of upper and lower
      airway. Aerosoltherapy is frequently prescribed and contribute to reach this aim.
      However educative action towards the patient and parents are also important in
      some situation.

PMID- 17508668
TI  - [Varenicline (Champix)].

PMID- 17508669
TI  - Clinical research in dentistry.

PMID- 17508670
TI  - Brush up on your communication skills.

PMID- 17508671
TI  - Shedding even more light on an orthodontic appliance.

PMID- 17508672
TI  - Practice-based research networks.

PMID- 17508673
TI  - A conversation with Ira Lamster. Interview by Elliott M Moskowitz.

PMID- 17508674
TI  - Bacterial contamination and decontamination of toothbrushes after use.
AB  - The purpose of this study was to determine the extent of bacterial contamination
      of toothbrushes after use and the efficacy of chlorhexidine and Listerine in
      decontaminating toothbrushes. The effectiveness of covering a toothbrush head
      with a plastic cap in preventing contamination was also evaluated. It was found
      that 70% of the used toothbrushes were heavily contaminated with different
      pathogenic microorganisms. Use of a cap leads to growth of opportunistic
      microorganisms like Pseudomonas aeruginosa, which may cause infection in the oral
      cavity. Overnight immersion of a toothbrush in chlorhexidine gluconate (0.2%) was
      found to be highly effective in preventing such microbial contamination.

PMID- 17508675
TI  - Simplified method for recording maxillomandibular relations in complete dentures.
AB  - A simplified technique for recording maxillomandibular relations in complete
      dentures is described. This technique enables the practitioner to construct a
      mandibular occlusal mini-rim directly in the mouth, to adjust it to the required
      vertical dimension and to record the maxillomandibular relations during a single
      appointment. The mandibular record is formed with wax, used to hold the occlusal
      vertical dimension anteriorly, and impression plaster, to record the centric
      relation posteriorly.

PMID- 17508676
TI  - Effect of different surfaces and surface applications on bonding strength of
      porcelain repair material.
AB  - This study was done to analyze the effect of different surfaces and different
      surface applications on the bonding strength of porcelain repair material and to
      compare these factors with one another. Three different substructures of 10 mm
      diameter and 4 mm thickness were used for the repair surface: metal, metal on
      porcelain and porcelain. The surfaces of half of the samples were roughened with
      an air abrasion tool; the surfaces of the other half were treated with a diamond
      bur. The specimens were ultrasonically cleaned in distilled water. A silane
      coupling agent and a bonding agent were applied to the surfaces of all the
      samples. Resin composite was applied to each specimen. All specimens were stored
      in distilled water for 24 hours before being thermocycled. After thermocycling,
      specimens were stored in distilled water for an additional seven days before
      being subjected to a shear load. The highest bonding strength was observed in the
      samples with a metal substructure, the surfaces of which were prepared with an
      air abrasion tool; the lowest bonding strength was observed in the samples with a
      metal substructure, the surfaces of which were prepared with a diamond bur. When
      different substructures were examined in terms of bonding strength, the highest
      bonding strength was statistically observed in metal-on-porcelain substructures,
      and the lowest bonding strength was observed in the porcelain substructure. When
      they were examined in terms of surface processes, the highest bonding strength
      was statistically observed in the samples whose surfaces were prepared with an
      air abrasion tool, and the lowest bonding strength was observed in the samples
      whose surfaces were prepared with a diamond bur.

PMID- 17508677
TI  - Alport syndrome. Report of a case with severe maxillofacial manifestations.
AB  - Alport syndrome (AS) represents a genetic cause of renal failure that affects
      about 1 in 5,000 Americans. In cases of AS, the problem resides on the X
      chromosome. Specific mutations to the gene cause defects in one of several
      subunits of Type IV collagen. Accumulation of collagen types V and VI, with
      subsequent abnormalities in the permeability and sclerosis of the kidney, leads
      to renal failure. Renal failure causes severe bone disease since the kidney
      processes vitamin D, which is necessary for calcium absorption from the
      intestine. Therefore, in a patient with chronic renal disease, vitamin D is not
      produced, resulting in a decrease in intestinal absorption of calcium and
      subsequent lower serum calcium levels. Furthermore, the decreased phosphate
      excretion by the kidney leads to elevation of plasma phosphate, which increases
      the amounts of parathyroid hormone required to move calcium from bone (secondary
      hyperparathyroidism) to maintain plasma calcium at a constant level and preserve
      an appropriate calcium-phosphorous ratio. We have described AS, reviewed the
      pathogenesis and presented an interesting extreme case with numerous craniofacial
      manifestations.

PMID- 17508678
TI  - Laser exposure of unerupted teeth.
AB  - Surgical soft tissue exposure of impacted teeth can now be performed with little
      to no discomfort and excellent postoperative healing. This paper focuses on the
      techniques used in performing this procedure.

PMID- 17508679
TI  - Early manifestation of pemphigus vulgaris. A case report.
AB  - Pemphigus vulgaris (PV) is traditionally viewed as an autoimmune disease of the
      skin, but it almost always involves the oral cavity. It can be fatal if left
      untreated and allowed to progress to advanced stages. Early recognition and
      intervention are essential for a favorable prognosis. Since oral lesions
      represent an initial manifestation of PV, dentists are in an ideal position to
      make an early diagnosis and initiate treatment. Here we report a case of PV that
      was diagnosed in its earliest stage.

PMID- 17508680
TI  - Clinical and radiographic evaluation of root perforation repair using MTA.
AB  - An accident that can occur during endodontic treatment is perforation, which
      adversely affects the prognosis of the teeth. A restorative material should be
      easy to use, nonresorbable, biocompatible, esthetically pleasing, and should
      provide a complete seal. Mineral trioxide aggregate (MTA) is a relatively new
      material that is being used successfully to repair perforation. The purpose of
      this study was to perform a clinical and radiographical evaluation of the success
      rate of root perforation repairs using mineral trioxide aggregate. Based upon the
      results of this study, MTA is a suitable material for root perforation repair and
      can be used confidently.

PMID- 17508681
TI  - [Allergy to cashew nuts and peanuts].
AB  - Anaphylaxis due to the ingestion of peanuts is a serious, common condition, known
      to both the general public and physicians. Recently, an increasing number
      ofpatients with an anaphylactic reaction after eating small amounts of cashew
      nuts have been reported. In three children, a boy aged 7 and two girls aged 9 and
      10 years, respectively, with heterogeneous case histories involving allergic
      upper airway and conjunctival symptoms and constitutional eczema, allergy for
      cashew nuts was diagnosed in the first two and allergy for peanuts in the third.
      They were given dietary advice and an adrenaline auto-injector for emergencies.
      In most cases, a detailed food history, together with the demonstration of IgE
      against cashew nuts by means of serology or skin prick tests, are sufficient to
      establish the diagnosis. If the clinical relevance of a sensitisation to cashew
      nuts is unknown, a food provocation test may be necessary. The treatment consists
      of dietary intervention, and an adrenaline auto-injector is prescribed for a
      serious anaphylactic reaction. So far, three major allergens from the cashew nut
      (Anacardium occidentale) have been identified and purified.

PMID- 17508682
TI  - [Estimating renal function with formulas].
AB  - A glomerular filtration rate (GFR) <60 ml/min/1.73 m2 is associated with an
      increased risk of cardiovascular disease and renal insufficiency. The formula of
      the 'Modification of diet in renal disease' (MDRD) study is derived from plasma
      creatinine concentrations and estimates GFR based on age, sex and race. Many
      clinical laboratories have started to report estimated GFR using this formula,
      which may lead to earlier recognition of chronic kidney disease. Clinicians
      should understand for which patients the MDRD formula may be appropriate and be
      aware of its limitations.

PMID- 17508683
TI  - [Benefits and risks of drug-eluting stents].
AB  - The March 8, 2007-issue of the New England Journal of Medicine contained 5
      original articles, 2 commentaries and 1 editorial on drug-eluting coronary stents
      versus bare metal stents. Over the past 5 years, multiple randomised, controlled
      trials have shown that drug-eluting stents reduce recurrent stenosis and the need
      for additional revascularisation procedures. Drug-eluting stents are now used in
      a large proportion of percutaneous coronary interventions. Following publications
      reporting a risk of late thrombosis with sudden occlusion, the promises and
      uncertainties regarding the benefits and risks are now heavily debated. It can be
      concluded that these first-generation drug-eluting stents, provided that they are
      used for indications in accordance with the randomised trials, result in a clear
      reduction in the need for additional revascularisation procedures without an
      effect on long-term case fatality and myocardial infarction. There is a small but
      serious risk of sudden thrombosis and occlusion. The task for the future will be
      to develop stents that do reduce recurrent stenosis but allow a normal
      endothelisation of the treated coronary artery segment. When drug-eluting stents
      have reached that stage, they will be clearly advantageous.

PMID- 17508684
TI  - [The use of antiviral agents during an (impending) influenza pandemic].
AB  - The preventive and therapeutic principles during an (impending) influenza
      pandemic differ fundamentally from those prevailing during the annual episodes
      ofinfluenza. Pending the availability of an effective pandemic vaccine,
      neuraminidase inhibitors are the only effective agents for the prevention and
      treatment of infections caused by a pandemic influenza virus. The development of
      an influenza pandemic has 6 phases: phases 3-5 reflect an increasing threat;
      phase 6 represents a manifest pandemic. During phases 3-5, a maximum effort is
      made to prevent or delay a pandemic. Neuraminidase inhibitors should be given not
      only to patients but also to their close contacts (post-exposure prophylaxis).
      During phase 6, post-exposure prophylaxis is no longer indicated and
      neuraminidase inhibitors are prescribed for all patients with symptoms ofpandemic
      influenza. Prophylaxis without preceding close contact with an influenza patient
      (primary prophylaxis) is recommended only in exceptional cases. Physicians should
      not prescribe antiviral drugs on demand to concerned citizens for stockpiling.

PMID- 17508685
TI  - [Diagnostic image (322). A neonate with a swelling on one leg. Kasabach Merritt
      syndrome].
AB  - A male neonate was born with a large blue-purple swelling at the upper left leg.
      This was accompanied by a severe thrombocytopenia, a microangiopathic hemolytic
      anemia and a consumption coagulopathy: Kasabach Merritt syndrome.

PMID- 17508686
TI  - [Dietary supplements are useful in the prevention and treatment of pressure
      sores].
AB  - The causal relationship between nutrition and pressure sores (PS) remains
      unclear. Nevertheless, it is evident that many acute and chronically ill
      patients, at risk of PS or with established PS, have undesirable weight loss and
      malnutrition. Providing extra nutritional supplements in addition to regular food
      intake seems a logical way to replenish body shortages of macro- and
      micronutrients as well as to supply extra nutrients for the preservation of skin
      tissue, strengthening oftissue resistance, and promoting tissue repair. This is
      relevant because malnourished patients, at risk of PS or with established PS,
      often have problems in fulfilling their nutritional needs by normal food intake.

PMID- 17508687
TI  - [Dietary supplements such as nutrient drinks have no role in the prevention of
      pressure sores].
AB  - Pressure sores are the result of primary intrinsic factors like pressure, shear
      and friction forces combined with secondary extrinsic factors such as old age,
      malnutrition, immobility, incontinence, and poor physical and mental health. A
      cause-and-effect relationship between malnutrition and decubitus ulcers has never
      been established. There is insufficient evidence that dietary interventions can
      decrease the incidence of pressure sores.

PMID- 17508688
TI  - [Estimating renal function based on creatinine clearance: application of
      different formulas and correction for obese patients].
AB  - OBJECTIVE: To determine whether glomerular filtration rate (GFR) is best
      estimated by the Cockcroft-Gault formula or the formula used in the 'Modification
      ofdiet in renal disease' (MDRD) study. DESIGN: Descriptive inventory. METHOD:
      Passing-Bablok regression analysis was performed using the statistics program
      'Analyse it' for the estimated GFR derived by both formulas based on 467 patients
      who had data on height, weight and creatinine clearance entered into the
      laboratory information system of the Maxima Medical Centre, Veldhoven, the
      Netherlands, during a 2-year period. The performance of each formula was analysed
      in different patient groups based on weight. RESULTS: The MDRD formula and the
      Cockcroft-Gault formula performed similarly in all weight groups with adequate
      precision, particularly when the corrected Cockcroft-Gault formula was used for
      patients with a body-mass index (BMI) >25 kg/m2. The fact that outcomes using the
      BMI-corrected Cockcroft-Gault formula strongly correlated with outcomes
      calculated using the so-called Salazar-Corcoran formula, which was developed
      specifically for use in obese patients, confirms the validity of the BMI
      corrected approach. CONCLUSION: The Cockcroft-Gault formula and the MDRD formula
      both provided appropriate estimates of GFR and were also considerably more
      suitable for screening for renal function than assessment of plasma creatinine
      concentration. However, the best non-invasive way to determine GFR remains a
      carefully performed assessment ofcreatinine clearance using plasma and 24-hour
      urine samples.

PMID- 17508689
TI  - [Assessment of renal function according to the NHG protocol 'Diabetes mellitus
      type 2': risk of overestimating the number of diabetes patients with renal
      dysfunction].
AB  - OBJECTIVE: To evaluate the consequences of the new Dutch College of General
      Practitioners (NHG) protocol 'Diabetes mellitus type 2', which recommends using
      either the Cockcroft-Gault (CG) formula or the 'Modification of diet in renal
      disease' (MDRD) study formula to determine the estimated glomerular filtration
      rate (eGFR) as an indicator of renal function, in a cohort of patients with type
      2 diabetes. DESIGN: Inventory. METHOD: The eGFR was calculated using the CG
      formula, the body-mass index (BMI-)corrected CG formula and the MDRD formula in
      6224 patients with type-2 diabetes who entered the 'Zwolle outpatient diabetes
      project integrating available care' (ZODIAC) study in 2005. RESULTS: Using the CG
      and MDRD formulas, 31% and 63% of patients, respectively, had an eGFR of 30-59
      ml/min (units for MDRD are ml/ min/1.73 m2) for which referral is advisable. In
      addition, 1% and 11%, respectively, had an eGFR <30 ml/min (reference: >90
      ml/min), for which referral is necessary. Most patients aged >70 years (or > 50
      years using the BMI-corrected CG formula) had an eGFR <60 ml/min. CONCLUSIONS:
      Reduced eGFR can be a sign of renal dysfunction but, using these formulas, can
      also be partly explained by advanced age. Therefore other factors should be
      considered when interpreting the results ofeGFR before it is concluded that the
      patient has kidney disease and the associated increased risk of cardiovascular
      disease.

PMID- 17508690
TI  - [Determining aldosterone in the adrenal veins in order to establish uni- or
      bilateral aldosterone production in patients with primary hyperaldosteronism].
AB  - In 3 patients, men aged 60, 55 and 60, respectively, with hypertension due to
      primary hyperaldosteronism, the aldosterone level in the adrenal veins was
      determined for the purpose of further diagnosis. In two patients, unilateral
      adrenal enlargement on the CT-scan was accompanied by overproduction
      ofaldosterone, in one case in a non-enlarged adrenal gland and in the other case
      in both adrenals. The first patient underwent adrenalectomy of the non-enlarged
      adrenal gland, while in the second patient surgery was decided against. The third
      patient had bilateral adrenal gland enlargement on the CT-scan with a surgically
      treatable, unilateral overproduction ofaldosterone. Now that determination ofthe
      aldosterone:renin ratio in plasma as a screening method in selected patients with
      hypertension is being used more often, primary hyperaldosteronism turns out to be
      more common than was previously thought. For differentiation between unilateral
      and bilateral overproduction of aldosterone, imaging of the adrenals, for example
      with CT, is insufficiently accurate. Aldosterone determination in the adrenal
      veins can distinguish between unilateral and bilateral overproduction of
      aldosterone with great accuracy, which has important therapeutic consequences.

PMID- 17508691
TI  - [Ambrosius Arnoldus Guilielmus Guye, editor-in-chief of the Dutch Journal of
      Medicine 1884-1889].
AB  - Ambrosius Arnoldus Guilielmus Guye (1839-1905) was the patriarch of
      otorhinolaryngology in The Netherlands. He designed various small surgical
      instruments and identified the disorder aprosexia, which brought him
      international recognition. He can be looked upon as a second-generation
      hygienist. During his brief period as editor-in-chief of The Nederlandsch
      Tijdschrift voor Geneeskunde (Dutch Journal of Medicine) (1884-1889), he
      introduced a more stable production process.

PMID- 17508692
TI  - [The technique is further than the knowledge].

PMID- 17508693
TI  - [Fractures in full-term neonates].

PMID- 17508694
TI  - ['The journal keeps the physicians well informed'].

PMID- 17508695
TI  - [Medical perception of the hereditary aspects of cancer in The Netherlands, 1900
      1980].

PMID- 17508696
TI  - Occupational exposure to ultraviolet radiation: the duality dilemma.
AB  - Human exposure to ultraviolet (UV) radiation is a component of everyday life and
      a significant hazard for outdoor workers. In addition, a large range of
      artificial sources also has the potential to provide extreme occupational UV
      exposure. Even though the human health risks of overexposure to UV are well
      documented, to date relatively little is known quantitatively about UV exposure.
      For example, the evidence indicates that workers who are exposed to particular
      sources (for example, welding arcs) are exposed to extreme UV exposures, despite
      the use of current control measures. In contrast, increasing evidence points to
      significant health impacts resulting from underexposure to UV, particularly with
      the production (or more correctly lack of production) of vitamin D in the skin.
      The latter poses a serious issue for the work-force, with specific risks for
      workers lacking adequate sun exposure-underground miners, long-haul flight crews,
      shift workers, and perhaps indoor workers. Using a risk-management approach, this
      paper provides a comprehensive review of occupational UV sources, health impact
      of occupational UV exposure, occupational exposure standards, and levels of
      exposure in various settings, and discusses the appropriate control measures. In
      addition, the duality aspect of health impacts from overexposure and
      underexposure to UV and the associated occupational health implications are
      specifically explored.

PMID- 17508697
TI  - Volatile organic compounds: do they present a risk to our health?
AB  - Indoor air quality has been recognised as a significant health, environment, and
      economic issue in many countries. Research findings have demonstrated that some
      air pollutants occur more frequently and at a higher concentration in indoor air
      than in outdoor air, including volatile organic compounds (VOCs). In this
      context, the indoor environment can be of crucial importance because modem
      society spends most of their time indoors, and exposure to VOCs may result in a
      spectrum of illnesses ranging from mild, such as irritation, to very severe
      effects, including cancer. These effects have been seen at very low levels of
      exposure in many epidemiological studies. In this review, we discuss the nature
      of the VOCs that are ubiquitous in indoor environment and the evidence for
      adverse health effects associated with exposure to some of these compounds.

PMID- 17508698
TI  - The interrelation between organophosphate toxicity and the epidemiology of
      depression and suicide.
AB  - The literature on an association between organophosphate (OP) toxicity and
      depression or suicide is scarce. An interrelation exists among populations
      exposed to OPs, acute OP toxicity, neurobehavioral effects, depression, suicide,
      and fatality. Acute OP toxicity is characterized by the cholinergic syndrome with
      systemic and central nervous system effects. Organophosphate-induced
      neurobehavioral effects result in depression. A potential risk of depression and
      suicide exists in farm workers exposed to OPs. The sociodemographics of
      depression include age, gender, race, geographic region, social factors,
      economics, psychiatric disorders, medical conditions, and hereditary factors.
      Suicide is a major consequence of depression, with multiple sociodemographic risk
      factors. Developing countries have a higher incidence of OP toxicity, with
      limited information on the prevalence of depression. In these countries, the
      incidence of suicide is high, affecting more females. Suicide is more prevalent
      in rural areas, and in farming communities, commonly with ingestion of OPs. In
      industrialized countries, the incidence of OP toxicity is lower, but the
      prevalence of depression is higher. Suicide rates are lower in industrialized
      countries, affecting more males, the urban population, and farming communities.
      Other lethal methods of suicide, such as hanging, firearms, electrocution, and
      drug overdose are more common in industrialized countries. A potential risk of
      depression or suicide certainly exists from OP toxicity, largely depending on the
      epidemiology or sociodemographics of these disorders. Scientific evidence shows
      that the association between environmental toxicology and psychiatry has
      important public health implications.

PMID- 17508699
TI  - A review of depleted uranium biological effects: in vitro and in vivo studies.
AB  - The use of depleted uranium in armor-penetrating munitions remains a source of
      controversy because of the numerous unanswered questions about its long-term
      health effects. Although no conclusive epidemiologic data have correlated DU
      exposure to specific health effects, studies using cultured cells and laboratory
      rodents continue to suggest the possibility of leukemogenic, genetic,
      reproductive, and neurological effects from chronic exposure. Until issues of
      concern are resolved with further research, the use of depleted uranium by the
      military will continue to be controversial.

PMID- 17508700
TI  - ["Better to be restless than locked up in a deep hole!" Understanding and therapy
      of attention deficit and hyperactivity disorder from a psychodynamic viewpoint].
AB  - Psychodynamic models will be presented after a critical discussion of the
      biomedical-psychiatric model of attention deficit and hyperactivity disorder
      (dimensional diagnostics, genetic disorder, dopamine deficiency, neuronal
      developmental disorder). Research findings on early mother-child interactions
      refer to specific psychosocial developmental conditions amongst children who
      develop ADHD. Factors which lead to gene expression can be traced here. A
      psychodynamic-oriented developmental psychotherapy which centres on regulatory
      procedures, de-centration, mentalisation, de-somatisation and symbolisation of
      treated notifications is helpful, particularly amongst children with complex
      disorders. The underlying conflicts and dealing with them are thus elucidated in
      the presentation of a treatment.

PMID- 17508701
TI  - [Psychodynamic models about the origins, internal processing and treatment of
      ADHD].
AB  - At first the symptoms of ADHD can be viewed as part of the natural expressive
      repertory of the infant. Later they merge with pathological relationship
      patterns. The pathology sets in--apart from genetic vulnerability--through flawed
      early interactions as well as early childhood trauma. In the attachment theory
      the results are termed as anxious ambivalent and disorganized attachments. The
      further course of ADHD remains dependent on the course of the child's
      relationships and forms itself in symbiotic and narcissistic reaction patterns.
      By means of impulsive-aggressive outbursts and restless inattentive behaviour the
      child tries to attract attention and evade attention, express hurt and take
      revenge in the same instant. Likewise the child may ward off traumatic memories
      or even protect himself from a depressive breakdown. During its prolonged use
      until adolescence medication can change from good to bad object and then at best
      serve to hide the existence of sadistic fantasies behind a well-mannered facade.

PMID- 17508702
TI  - [Psychoanalytic psychotherapy and the ADHD-triad (impulsivity, hyperactivity and
      attention deficit disorder)].
AB  - A brief survey of the psychoanalytically oriented literature regarding the
      symptom triad of ADHD is followed by the discussion of frequently found
      disturbances in infantile development, attachment, object relations (regulation
      of drives and affects, ego functions) of the role of infantile trauma (object
      loss) and psychic conflict. In the analytic-psychotherapeutic process with a
      child, the ADHD-symptom-triad may manifest itself e.g. as intrapsychic conflict
      on the level of the self-representation or of the representation of central self
      object-relations (characterized by an insufficient containing-/holding-function),
      as impairment of self-regulative functions, as inconsistent symbolizing capacity
      or as deficient regulating and controlling capacity of the ego. The multitude of
      factors involved does not allow a generalisation of neither the etiology or the
      pathogenesis of this symptom triad. This is particularly evident in a therapeutic
      procedure which is relation oriented. In a first interview the authors illustrate
      the capacity of a ten year old boy (diagnosed as ADHD patient) to make use of the
      analytic therapeutic dialogue and to present his intrapsychic experiences and
      problems in a figurative and narrative performance. Finally some specific
      technical features of low or high frequent analytic psychotherapy with ADHD
      children are shown: according to the foremost pregenital form of relations-
      manifested mostly by intensive self esteem problems, narcissistic aggressiveness
      and motor impulsivity--the transference and counter-transference movements
      proceed predominantly by projective and introjective identifications. Containment
      of the difficulties by the therapist is often paralleled for a long period of
      time by assistance in regulation and by limit setting for the child. Translation
      of action into language and transformation of intrapsychic processes within the
      psyche of the therapist into helpful interventions for the child require a
      continuous adjustment to the inconsistent ego functions and the fragile self
      esteem of the child. The additional use of stimulant drugs, the work within the
      family and/or the social context and the high need for research in the analytical
      field are briefly discussed at the end.

PMID- 17508703
TI  - [Between empathy and setting limits--reflections on psychodynamics and treatment
      techniques in psychoanalytic therapies for hyperkinetic disorders].
AB  - The rise in "hyperkinetic disorder" diagnoses is not based on better but rather
      on less precise diagnoses. As a rule the co-morbidities as mentioned in ICD-10
      like emotional disorders, commitment disorders and social behaviour disorders,
      are the real clinical pictures accompanied by such symptoms as inattentiveness,
      hyperactivity and impulsiveness. These are disorder pictures based possibly on
      unconscious areas of conflict which can be managed by psychoanalytic treatment.
      However, this involves considerable treatment challenges taking into account that
      there are some major difficulties: Children showing said disorder pictures have
      not only symbolizing disorders but mostly also playing disorders. They experience
      playing not symbolically, no longer mainly "as if" and taking place in a space
      between imagination and reality. Their play may easily turn into concreteness or
      reality and get out of control all of a sudden. In addition, children and young
      people with externalizing disorders constantly attack basic conditions and seek
      to destroy them. Verbal intervention frequently does not reach the patients.
      Counter transferences are very difficult to bear and to control, and the tendency
      of psychotherapists to join in is strong. It is therefore of great importance to
      work on the ability of symbolization and mentalization, on relationship and
      transference, simultaneously however on frame and structure, with reliability and
      regularity of the settings. Analytic therapies as well as therapies founded on
      depth psychology may be indicated, possibly supplemented by parallel medication;
      at the beginning a particularly careful diagnosis should be made.

PMID- 17508704
TI  - [ADHD--indication for psychoanalytic treatments? Some clinical, conceptual, and
      empirical considerations based on the "Frankfurt Prevention Study"].
AB  - Based on clinical experiences, results of the Frankfurt Prevention Study and
      arguments taken from a current interdisciplinary dialogue between psychoanalysis
      and neurobiology the authors discuss that Attention Deficit Hyperactivity
      Disorder (ADHD) always has to be understood as a product of complex interactions
      of (mostly unconscious) idiosyncratic, biographical, relational, institutional,
      societal as well as neurobiological, neurophysiological, and genetical factors.
      This is one reason why the authors think that psychoanalysis with its unique
      conceptualizations to understand psychic realities as products of such a complex
      intertwining of unconscious and reality factors, taking into account biological
      as well as societal roots of human behavior, could be regarded as one of the best
      available psychotherapeutic approach nowadays which is capable to deal
      theoretically and therapeutically with children suffering from ADHD.
      Psychoanalysis offers an alternative (with longlasting positive results) to
      exclusive treatments with psychostimulants. This thesis is discussed by short
      case studies illustrating 7 subgroups of children with very different inner
      conflicts and fantasies all being subsumed under the ADHD diagnosis in DSM-IV.

PMID- 17508705
TI  - Relationship between tooth loss/probing depth and systemic disorders in
      periodontal patients.
AB  - During the last decades, many published studies have focused on the associations
      between periodontal disease and different systemic disorders. The purpose of the
      present investigation was to study the relationship between occurrence of
      systemic disorders and the two variables mean number of teeth and periodontal
      probing pocket depth after stratification according to smoking habits. The study
      was conducted as a retrospective study based on consecutive selection of patients
      at a specialist clinic of Periodontology. The study population consisted of 1854
      individuals. Of these, 797 were males, and 1057 were females. Multiple regression
      analyses were adopted in order to calculate the partial correlations between the
      number of remaining teeth/the relative frequency of periodontal probing depths >
      or = 5 mm and presence of systemic disease for different strata according to sex
      and smoking habits with age included as an independent variable. Non-smoking men
      with cardiovascular disease, diabetes and rheumatoid disease had significantly
      fewer teeth compared to non-smoking men without systemic disorder. In conclusion,
      cardio-vascular disease, diabetes and rheumatoid disease may be regarded as risk
      indicators of tooth loss in men. However, in order to investigate hypotheses
      concerning potential risk factors, emerging from cross-sectional studies, being
      true risk factors of tooth loss, longitudinal prospective studies including
      established risk factors along with new exposures of interest as covariates are
      required.

PMID- 17508707
TI  - Patients' health in contract and fee-for-service care. I. A descriptive
      comparison.
AB  - Fee-for-service care, paying afterwards for services provided, is the traditional
      adult patient financial system in dentistry in Sweden. The public dental health
      service (PDHS) in the county of Varmland has since 1999 also an alternative
      system, contract care. There, a fixed sum of money is paid annually for dental
      care, which then is received without additional costs. This study compares the
      demographics, general health and oral health-related quality of life (OHRQoL) in
      the patient financial systems fee-for-service and contract care in the PDHS in
      Varmland. A questionnaire was answered by 1,324 patients, response rate 57%. A
      non-response analysis was undertaken. The non-response analysis showed that the
      likelihood for answering the questionnaire was higher for women, for respondents
      in contract care and for increasing age. Further analyses revealed that the non
      respondents were healthier than the respondents and that experience of pain in
      the mouth was the only variable increasing the likelihood of response. General
      health was studied with the SF-36 and OHRQoL with the OHIP-14. The demographics
      studied were gender, age, birth country, marital status, education and social
      network. The results showed that there were differences in patients' health
      between the patient financial systems. Respondents in contract care had better
      OHRQoL than those in fee-for-service care. They also had better general health in
      four of the dimensions of SF-36, were younger, better educated, born in Sweden
      and were married/living with somebody to a larger extent than fee-for-service
      care respondents. Fee-for-service care respondents experienced higher social
      affinity with their housing area. In conclusion, patients in contract care had
      better general health and OHRQoL than patients in fee-for-service care. There
      were social differences in choice of financial system and biased non-response.

PMID- 17508708
TI  - Subjective evaluation of orthodontic treatment and potential side effects of
      bonded lingual retainers.
AB  - The primary aim of this study was to evaluate our patients' experience of their
      treatment period with a fixed appliance and their opinions about the results five
      years after completion of active treatment. A second aim was to assess bonded
      lingual retainers and their potential side effects. A final aim was to compare
      the results in a postgraduate clinic (Goteborg) and a specialist clinic
      (Vanersborg). This study included 170 patients who finished their active
      treatment in 1997-1998. Eighty-three patients were from Goteborg (postgraduate
      clinic) and 87 from Vanersborg (specialist clinic). The patients were examined
      for visible calculus, approximal caries in the anterior regions, gingival
      recessions and the status of existing retainers in the upper and lower anterior
      teeth. All patients completed a questionnaire and were interviewed after
      undergoing a clinical examination. The statistical methods used were descriptive
      analysis and the chi-square test. The main reason for orthodontic treatment was
      appearance and most patients (94%) were satisfied with their treatment result.
      Our results showed a significantly higher frequency of loosened or fractured
      retainers at the postgraduate clinic compared to the specialist clinic (p <
      0.01), which might be explained by operator sensitivity in bonding retainers.
      There was a tendency for calculus to develop more easily with than without
      retainers. CONCLUSION: Patient satisfaction of the treatment given at the
      postgraduate clinic was the same as at the specialist clinic except for more
      frequent loosening of bonded retainers.

PMID- 17508706
TI  - A four-year cohort study of caries and its risk factors in adolescents with high
      and low risk at baseline.
AB  - AIM: To report and compare risk and preventive factors for caries in high- and
      low-risk adolescents, from a 4-year cohort study on commonly used preventive
      measures for caries in adolescents in the Swedish Public Dental Service. SUBJECTS
      AND METHODS: In 1995 a cohort of 12-year-olds was examined for caries and
      completed a questionnaire. This procedure was repeated at age 14 and 16. The
      group identified as being at high risk was examined every year and this group was
      randomly assigned to one of four preventive programs. The outcomes examined were
      the caries increments using the DMF-indices. Poisson regression was used to
      assess risk and preventive factors. RESULTS: The number of 12-year-olds
      participating was 3,373 in 1995 and 2,848 were still participating in 1999. A
      higher risk of caries increment was observed for adolescents from working-class
      homes, from outside Western Europe, and for those who often ate candy and did not
      brush their teeth twice a day. Important findings were the different results for
      the preventive factors when different DMF-indices were used as outcome measures
      and the fact that there was no difference between the high-risk group and the
      total group when it came to risk or preventive factors. The clinically tested
      prevention had a low effect i.e., the semi-annual application of fluoride varnish
      prevented 10% of the dentine and enamel caries development over 4 years.

PMID- 17508709
TI  - Oral status and treatment needs among elderly within municipal long-term care
      2002-2004.
AB  - A supplementary regulation in the Swedish National Dental Health Care Insurance
      stipulates an increased economic support to those, who are dependent permanently
      due to disease or handicap. Once enlisted to care, they are entitled to an annual
      dental examination and individual prophylactic advice free of charge, and to
      necessary dental treatment, offered within the ordinary medical care, regulated
      and funded by the county council. A population of persons, > or = 65 years of age
      and enrolled in municipal long-term care (LTC) in a county in the south of
      Sweden, was followed regarding changes in oral status and treatment needs for two
      years. The number of persons examined the year 2002 was 2416 and the
      corresponding figure for 2004 was 2846. Totally 1170, i.e. 48.4%, of those
      examined 2002 were deceased two years after the initial examination. Only 914,
      assessed in 2002, were available for assessment with full data at follow up 2004
      and the results are based upon assessments in this group. Analyzing the assessed
      variables (dental status, oral hygiene status, oral mucosal inflammation, oral
      mucosal friction) revealed a change during these two years. Significant
      impairments were recognised, regarding mucosal inflammation and mucosal friction.
      Regarding treatment needs assessed by a dentist and a dental hygienist, there was
      a maintained and even increased need for extensive treatment, both by the dentist
      and, to a greater extent, by the dental hygienist. In sum, prevention efforts
      both from the dental profession and from other care providers are important to
      achieve and maintain acceptable oral status.

PMID- 17508710
TI  - Synthesis and testing of a binary catalytic system for imaging of signal
      amplification in vivo.
AB  - We report a binary targeted enzymatic system that is composed of two covalent
      monoclonal antibody conjugates for specific labeling of cellular targets in vivo.
      The system utilizes low-molecular weight peroxidase-reducing substrates
      synthesized by linking 5-hydroxytryptamine (serotonin) with DTPA (5HT-DTPA) for
      magnetic resonance and radionuclide imaging or with Cy5.5 for near-infrared
      optical imaging. Initially, the conjugation reaction conditions were optimized to
      achieve a low level of antiepidermal growth factor receptor (EGFR) antibody (EMD
      72000) modification with the N-hydroxysuccinimide ester of 4-hydrazinonicotinate
      acetone hydrazone (SANH), yielding mAb-HNH conjugate. The resultant modified
      antibodies were incubated with the periodate-oxidized peroxidase (HRP) or 4
      formylbenzoyl-conjugated glucose oxidase (GO), followed by the purification of
      the resultant mAb-enzyme conjugates by size-exclusion HPLC. The conjugates were
      further characterized by electrophoresis and were tested by cross-titration on
      A431 EGFR+ squamous carcinoma or SW620 adenocarcinoma cells (negative control).
      The conjugates at the optimized concentration ratios were further tested using
      near-infrared fluorescence microscopy in the presence of Cy5.5 monocarboxy-5
      hydroxytryptamide. Further in vitro experiments demonstrated that (1) antibody
      binding was specific and could be inhibited by free antibody; (2) both antibody
      conjugates exhibited high enzymatic activity after the binding to the cells; (3)
      111In-labeled 5-HT-DTPA was avidly binding to EGFR-positive cells only if both
      HRP- and GO-conjugates were bound to the cells. The conjugates were tested in
      vivo using a SPECT imaging experiment, which demonstrated the accumulation of
      111In-labeled 5-HT-DTPA substrate at the site containing both conjugates.

PMID- 17508711
TI  - Design and synthesis of efficient fluorescent dyes for incorporation into DNA
      backbone and biomolecule detection.
AB  - We report here the design and synthesis of a series of pi-conjugated fluorescent
      dyes with D-A-D (D, donor; A, acceptor), D-pi-D, A-pi-A, and D-pi-A for
      applications as the signaling motif in biological-synthetic hybrid foldamers for
      DNA detection. The Horner-Wadsworth-Emmons (HWE) reaction and Knoevenagel
      condensation were demonstrated as the optimum ways for construction of long pi
      conjugated systems. Such rodlike chromophores have distinct advantages, as their
      fluorescence properties are not quenched by the presence of DNA. To be
      incorporated into the backbone of DNA, the chromophores need to be reasonably
      soluble in organic solvent for solid-phase synthesis, and therefore a strategy of
      using flexible tetraethylene glycol (TEG) linkers at either end of these rodlike
      dyes was developed. The presence of TEG facilitates the protection of the chain
      growing hydroxyl group with DMTrCl (dimethoxytrityl chloride) as well as the
      activation of the coupling step with phosphoramidite chemistry on an automated
      DNA synthesizer. To form fluorescence resonance energy transfer (FRET) pairs, six
      synthetic chromophores with blue to red fluorescence have been developed, and
      those with orthogonal fluorescent emission were chosen for incorporation into DNA
      chromophore hybrid foldamers.

PMID- 17508712
TI  - Flow cytometry of HEK 293T cells interacting with polyelectrolyte multilayer
      capsules containing fluorescein-labeled poly(acrylic acid) as a pH sensor.
AB  - Polyelectrolyte multilayer sensor capsules, 5 microm in diameter, which contained
      fluorescein-labeled poly(acrylic acid) (PAAAF) as pH-sensitive reporter
      molecules, were fabricated and employed to explore their endocytotic uptake into
      HEK 293T cells by flow cytometry. The percentage of capsules residing in the
      endolysosomal compartment was estimated from the fluorescence intensity decrease
      caused by acidification. Capsules attached to the extracellular surface of the
      plasma membrane were identified by trypan blue quenching. The number of capsules
      in the cytoplasm was rather small, being below the detection limit of the method.
      The advantages of polyelectrolyte multilayer capsules are that the fluorophore is
      protected from interaction with cellular compartments and that the multilayer can
      be equipped with additional functions.

PMID- 17508714
TI  - Ultratrace determination of inorganic selenium without signal calibration.
AB  - To more readily evaluate the complex biogeochemistry of selenium, a flow-through
      electrochemical method was developed that can accurately determine Se(IV)
      concentrations in aqueous samples to part-per-trillion levels without signal
      calibration. Stripping methods were used in conjunction with a high-efficiency,
      flow-through cell. The cell was designed with a novel gold working electrode that
      was separated from a porous counter electrode by a Nafion membrane. Because this
      design permitted exhaustive deposition of selenium from the sample stream as well
      as efficient coulometric stripping, determinations obeyed Faraday's law over a
      reasonably wide range of operating conditions. The method had a minimum
      quantitation limit of approximately 8 ng and a maximum limit of 800 ng for
      Se(IV). It was reliable for sample volumes as small as 0.5 mL and as high as 20
      mL, thereby allowing determinations from part-per-million to just below part-per
      billion levels. Interferences from Cu(II) and arsenate were evident, but only
      when these species were present at concentrations exceeding 10 mg.L-1. Overall,
      the method had a performance comparable to hydride-generation atomic absorption
      spectrometry but with less cumbersome equipment and freedom from calibration.

PMID- 17508715
TI  - Laser-induced mixing in microfluidic channels.
AB  - We demonstrate a novel strategy for mixing solutions and initiating chemical
      reactions in microfluidic systems. This method utilizes highly focused nanosecond
      laser pulses from a Q-switched Nd:YAG laser at lambda = 532 nm to generate
      cavitation bubbles within 100- and 200-microm-wide microfluidic channels
      containing the parallel laminar flow of two fluids. The bubble expansion and
      subsequent collapse within the channel disrupts the laminar flow of the parallel
      fluid streams and produces a localized region of mixed fluid. We use time
      resolved imaging and fluorescence detection methods to visualize the mixing
      process and to estimate both the volume of mixed fluid and the time scale for the
      re-establishment of laminar flow. The results show that mixing is initiated by
      liquid jets that form upon cavitation bubble collapse and occurs approximately 20
      micros following the delivery of the laser pulse. The images also reveal that
      mixing occurs on the millisecond time scale and that laminar flow is re
      established on a 50-ms time scale. This process results in a locally mixed fluid
      volume in the range of 0.5-1.5 nL that is convected downstream with the main flow
      in the microchannel. We demonstrate the use of this mixing technique by
      initiating the horseradish peroxidase-catalyzed reaction between hydrogen
      peroxide and nonfluorescent N-acetyl-3,7-dihydroxyphenoxazine (Amplex Red) to
      yield fluorescent resorufin. This approach to generate the mixing of adjacent
      fluids may prove advantageous in many microfluidic applications as it requires
      neither tailored channel geometries nor the fabrication of specialized on-chip
      instrumentation.

PMID- 17508716
TI  - Ion-selective electrodes with three-dimensionally ordered macroporous carbon as
      the solid contact.
AB  - Electrodes with three-dimensionally ordered macroporous (3DOM) carbon as the
      intermediate layer between an ionophore-doped solvent polymeric membrane and a
      metal contact are presented as a novel approach to solid-contact ion-selective
      electrodes (SC-ISEs). Due to the well-interconnected pore and wall structure of
      3DOM carbon, filling of the 3DOM pores with an electrolyte solution results in a
      nanostructured material that exhibits high ionic and electric conductivity. The
      long-term drift of freshly prepared SC-ISEs with 3DOM carbon contacts is only
      11.7 microV/h, and does not increase when in contact with solution for 1 month,
      making this the most stable SC-ISE reported so far. The electrodes show good
      resistance to the interference from oxygen. Moreover, in contrast to previously
      reported SC-ISEs with conducting polymers as the intermediate layer, 3DOM carbon
      is an electron conductor rather than a semiconductor, eliminating any light
      interference.

PMID- 17508718
TI  - Quantitative in vivo microsampling for pharmacokinetic studies based on an
      integrated solid-phase microextraction system.
AB  - An integrated microsampling approach based on solid-phase microextraction (SPME)
      was developed to provide a complete solution to highly efficient and accurate
      pharmacokinetic studies. The microsampling system included SPME probes that are
      made of poly(ethylene glycol) (PEG) and C18-bonded silica, a fast and efficient
      sampling strategy with accurate kinetic calibration, and a high-throughput
      desorption device based on a modified 96-well plate. The sampling system greatly
      improved the quantitative capability of SPME in two ways. First, the use of the
      C18-bonded silica/PEG fibers minimized the competition effect from analogues of
      the target analytes in a complicated sample matrix such as blood or plasma
      samples, which is a common problem associated with solid coating SPME fibers for
      quantitative analysis. Moreover, the C18-bonded silica/PEG fibers provide high
      sensitivity and a large dynamic range that covers the possible sample
      concentration range during diazepam administration and elimination. Second, the
      kinetic calibration method offers more accurate quantitation than the calibration
      curve method for in vivo SPME, because it compensates for convection and matrix
      effects during sampling. Therefore, it is especially suitable as a fast sampling
      technique for pre-equilibrium SPME. Furthermore, with the high-throughput
      desorption device, the integrated system offers compactness and high efficiency.
      Its feasibility for in vivo sampling was demonstrated by monitoring diazepam
      pharmacokinetics and validated by conventional chemical assays and equilibrium
      SPME. In addition, we propose a simple method to determine the apparent
      distribution constant between an SPME fiber and a blood matix (Kfs) and the
      distribution constant between an SPME fiber and a pure PBS buffer sample matrix
      (Kfb). As a result, both total and free concentrations of the drug and its
      metabolites can be detected simultaneously. Accordingly, the binding constants to
      the blood matrix can be obtained, which are of special significance for clinical
      diagnosis and drug discovery.

PMID- 17508719
TI  - DNA nanoswitch as a biosensor.
AB  - We present a new type of DNA switch, based on the Holliday junction, that uses a
      combination of binding and conformational switching to enable specific label-free
      detection of DNA and RNA. We show that a single RNA oligonucleotide species can
      be detected in a complex mixture of extracted cellular RNA and demonstrate that
      by exploiting different aspects of the switch characteristics we can achieve 30
      fold discrimination between single-nucleotide mismatches in a DNA
      oligonucleotide.

PMID- 17508717
TI  - Probing ligand binding to duplex DNA using KMnO4 reactions and electrospray
      ionization tandem mass spectrometry.
AB  - An electrospray ionization tandem mass spectrometry (ESI-MS/MS) strategy
      employing the thymine-selective KMnO4 oxidation reaction to detect conformational
      changes and ligand binding sites in noncovalent DNA/drug complexes is reported.
      ESI-MS/MS is used to detect specific mass shifts of the DNA ions that are
      associated with the oxidation of thymines. This KMnO4 oxidation/ESI-MS/MS
      approach is an alternative to conventional gel-based oxidation methods and
      affords excellent sensitivity while eliminating the reliance on radiolabeled DNA.
      Comparison of single-strand versus duplex DNA indicates that the duplexes exhibit
      a significant resistance to the reaction, thus confirming that the oxidation
      process is favored for unwound or single-strand regions of DNA. DNA complexes
      containing different drugs including echinomycin, actinomycin-D, ethidium
      bromide, Hoechst 33342, and cis-C1 were subjected to the oxidation reaction.
      Echinomycin, a ligand with a bisintercalative binding mode, was found to induce
      the greatest KMnO4 reactivity, while Hoechst 33342, a minor groove binder, caused
      no increase in the oxidation of DNA. The oxidation of echinomycin/DNA complexes
      containing duplexes with different sequences and lengths was also assessed.
      Duplexes with thymines closer to the terminal ends of the duplex demonstrated a
      greater increase in the degree of oxidation than those with thymines in the
      middle of the sequence. Collisional activated dissociation (CAD) and infrared
      multiphoton dissociation (IRMPD) experiments were used to determine the site of
      oxidation based on oligonucleotide fragmentation patterns.

PMID- 17508720
TI  - Enantioselective determination of anteiso fatty acids in food samples.
AB  - Anteiso fatty acids (aFAs)-long-chain carboxylic acids with a methyl branch on
      the (n - 2)-carbon-are among the most simple fatty acids that are chiral. The
      most frequently occurring aFAs in food are 12-methyltetradecanoic acid (a15:0)
      and 14-methylhexadecanoic acid (a17:0), structures where the asymmetric carbon is
      more than 10 carbons separated from the polar head group. Previously, only
      enantioseparation of 4-methyl-substituted carboxylic fatty acids has been
      reported by gas chromatography. Here we present the first direct partial
      enantioresolution of synthesized racemic a15:0-a17:0 on a capillary column coated
      with 50% heptakis(6-O-tert-butyldimethylsilyl-2,3-di-O-methyl)-beta-cyclodextrin
      diluted in OV1701. Synthesized (S)-(+)-enantiomers were used to demonstrate that
      the elution order was (R)- prior to (S)-enantiomers. Using this system, food
      samples (butter, goat's milk fat, suet, human milk, seal oil, cod liver oil)
      known to contain aFAs were analyzed. Prior to the enantioselective gas
      chromatography, unsaturated fatty acids were preseparated by urea complexation,
      silver ion high performance liquid chromatography (Ag+-HPLC), or both from food
      samples. The fractions of the food samples enriched with methyl-branched fatty
      acids were then analyzed by GC/MS in the SIM mode. The measurements confirmed
      that the (S)-enantiomer of a15:0 (ee >96%), a16:0, and a17:0 (ee >90%,
      respectively) dominated in all samples. While the (R)-enantiomers could not be
      identified in samples from ruminants and human milk, their presence could be
      established in cod liver and seal oil (ee <86%).

PMID- 17508721
TI  - Cantilever-based sensor for the detection of different chromophore isomers.
AB  - We report the use of microcantilevers (MCs) for the detection of three retinoid
      isomers: 9-cis-retinal, 13-cis-retinal and all-trans-retinal. Detection of
      synthetic and natural retinoids in topical cosmetic products is important, and
      their presence can be used to predict reactions with the skin surface. In this
      study the MC surfaces were functionalized in order to promote the formation of
      covalent bonds with the chromophores. The lowest mass shift we detected with the
      functionalized MCs was 1.2 ppt, which is in the range needed by the cosmetics
      industry. Our results indicate that properly designed and functionalized
      microcantilevers can be used to construct economical, fast, and sensitive sensors
      for quality control in cosmetics.

PMID- 17508722
TI  - Water analysis: emerging contaminants and current issues.

PMID- 17508723
TI  - Diazene (HN=NH) is a substrate for nitrogenase: insights into the pathway of N2
      reduction.
AB  - Nitrogenase catalyzes the sequential addition of six electrons and six protons to
      a N2 that is bound to the active site metal cluster FeMo-cofactor, yielding two
      ammonia molecules. The nature of the intermediates bound to FeMo-cofactor along
      this reduction pathway remains unknown, although it has been suggested that there
      are intermediates at the level of reduction of diazene (HN=NH, also called
      diimide) and hydrazine (H2N-NH2). Through in situ generation of diazene during
      nitrogenase turnover, we show that diazene is a substrate for the wild-type
      nitrogenase and is reduced to NH3. Diazene reduction, like N2 reduction, is
      inhibited by H2. This contrasts with the absence of H2 inhibition when
      nitrogenase reduces hydrazine. These results support the existence of an
      intermediate early in the N2 reduction pathway at the level of reduction of
      diazene. Freeze-quenching a MoFe protein variant with alpha-195His substituted by
      Gln and alpha-70Val substituted by Ala during steady-state turnover with diazene
      resulted in conversion of the S = 3/2 resting state FeMo-cofactor to a novel S =
      1/2 state with g1 = 2.09, g2 = 2.01, and g3 approximately 1.98. 15N- and 1H-ENDOR
      establish that this state consists of a diazene-derived [-NHx] moiety bound to
      FeMo-cofactor. This moiety is indistinguishable from the hydrazine-derived [-NHx]
      moiety bound to FeMo-cofactor when the same MoFe protein is trapped during
      turnover with hydrazine. These observations suggest that diazene joins the normal
      N2-reduction pathway, and that the diazene- and hydrazine-trapped turnover states
      represent the same intermediate in the normal reduction of N2 by nitrogenase.
      Implications of these findings for the mechanism of N2 reduction by nitrogenase
      are discussed.

PMID- 17508724
TI  - Erythroid-specific expression of beta-globin by the sleeping beauty transposon
      for Sickle cell disease.
AB  - Sickle cell disease (SCD) results predominately from a single monogenic mutation
      that affects thousands of individuals worldwide. Gene therapy approaches have
      focused on using viral vectors to transfer wild-type beta- or gamma-globin
      transgenes into hematopoietic stem cells for long-term expression of the
      recombinant globins. In this study, we investigated the use of a novel nonviral
      vector system, the Sleeping Beauty (SB) transposon (Tn) to insert a wild-type
      beta-globin expression cassette into the human genome for sustained expression of
      beta-globin. We initially constructed a beta-globin expression vector composed of
      the hybrid cytomegalovirus (CMV) enhancer chicken beta-actin promoter (CAGGS) and
      full-length beta-globin cDNA, as well as truncated forms lacking either the 3' or
      3' and 5' untranslated regions (UTRs), to optimize expression of beta-globin.
      Beta-globin with its 5' UTR was efficiently expressed from its cDNA in K-562
      cells induced with hemin. However, expression was constitutive and not erythroid
      specific. We then constructed cis SB-Tn-beta-globin plasmids using a minimal beta
      globin gene driven by hybrid promoter IHK (human ALAS2 intron 8 erythroid
      specific enhancer, HS40 core element from human alphaLCR, ankyrin-1 promoter),
      IHbetap (human ALAS2 intron 8 erythroid-specific enhancer, HS40 core element from
      human alphaLCR, beta-globin promoter), or HS3betap (HS3 core element from human
      betaLCR, beta-globin promoter) to establish erythroid-specific expression of beta
      globin. Stable genomic insertion of the minimal gene and expression of the beta
      globin transgene for >5 months at a level comparable to that of the endogenous
      gamma-globin gene were achieved using a SB-Tn beta-globin cis construct.
      Interestingly, erythroid-specific expression of beta-globin driven by IHK was
      regulated primarily at the translational level, in contrast to post
      transcriptional regulation in non-erythroid cells. The SB-Tn system is a
      promising nonviral vector for efficient genomic insertion conferring stable,
      persistent erythroid-specific expression of beta-globin.

PMID- 17508725
TI  - Biglutaminyl-biliverdin IX alpha as a heme degradation product in the dengue
      fever insect-vector Aedes aegypti.
AB  - Hemoglobin digestion in the midgut of hematophagous animals results in the
      release of its prosthetic group, heme, which is a pro-oxidant molecule. Heme
      enzymatic degradation is a protective mechanism that has been described in
      several organisms, including plants, bacteria, and mammals. This reaction is
      catalyzed by heme oxygenase and results in formation of carbon monoxide, ferrous
      ion, and biliverdin IXalpha. During digestion, a large amount of a green pigment
      is produced and secreted into the intestinal lumen of Aedes aegypti adult
      females. In the case of another blood-sucking insect, the kissing-bug Rhodnius
      prolixus, we have recently shown that heme degradation involves a complex pathway
      that generates dicysteinyl-biliverdin IX gamma. The light absorption spectrum of
      the Aedes purified pigment was similar to that of biliverdin, but its mobility on
      a reverse-phase chromatography column suggested a compound less hydrophobic than
      biliverdin IXalpha. Structural characterization by ESI-MS revealed that the
      mosquito pigment is the alpha isomer of biliverdin bound to two glutamine
      residues by an amide bond. This biglutaminyl-biliverdin is formed by oxidative
      cleavage of the heme porphyrin ring followed by two subsequent additions of
      glutamine residues to the biliverdin IXalpha. The role of this pathway in the
      adaptation of this insect vector to a blood-feeding habit is discussed.

PMID- 17508726
TI  - 2-Hydroxychromene-2-carboxylic acid isomerase: a kappa class glutathione
      transferase from Pseudomonas putida.
AB  - The enzyme 2-hydroxychromene-2-carboxylic acid (HCCA) isomerase catalyzes the
      glutathione (GSH)-dependent interconversion (Keq = 1.5) of HCCA and trans-o
      hydroxybenzylidene pyruvic acid (tHBPA) in the naphthalene catabolic pathway of
      Pseudomonas putida. The dimeric protein binds one molecule of GSH very tightly
      (Kd approximately 5 nM) and a second molecule of GSH with much lower affinity (Kd
      approximately 2 to 11 microM). The enzyme is unstable in the absence of GSH. The
      turnover number in the forward direction (47 s(-1) at 25 degrees C) greatly
      exceeds off rates for GSH (koff approximately 10(-3) to 10(-2) s(-1) at 10
      degrees C), suggesting that GSH acts as a tightly bound cofactor in the reaction.
      The crystal structure of the enzyme at 1.7 A resolution reveals that the
      isomerase is closely related to class kappa GSH transferases. Diffraction quality
      crystals could only be obtained in the presence of GSH and HCCA/tHBPA. Clear
      electron density is seen for GSH. Electron density for the organic substrates is
      located near the GSH and is best modeled to include both HCCA and tHBPA at
      occupancies of 0.5 for each. Although there is no electron density connecting the
      sulfur of GSH to the organic substrates, the sulfur is located very close (2.78
      A) to C7 of HCCA. Taken together, the results suggest that the isomerization
      reaction involves a short-lived covalent adduct between the sulfur of GSH and C7
      of the substrate.

PMID- 17508728
TI  - Computational studies of intramolecular hydrogen atom transfers in the beta
      hydroxyethylperoxy and beta-hydroxyethoxy radicals.
AB  - The beta-hydroxyethylperoxy (I) and beta-hydroxyethoxy (III) radicals are
      prototypes of species that can undergo hydrogen atom transfer across their
      intramolecular hydrogen bonds. These reactions may play an important role in both
      the atmosphere and in combustion systems. We have used density functional theory
      and composite electronic structure methods to predict the energetics of these
      reactions, RRKM/master equation simulations to model the kinetics of chemically
      activated I, and variational transition state theory (TST) to predict thermal
      rate constants for the 1,5-hydrogen shift in I (Reaction 1) and the 1,4-hydrogen
      shift in III (Reaction 2). Our multi-coefficient Gaussian-3 calculations predict
      that Reaction 1 has a barrier of 23.59 kcal/mol, and that Reaction 2 has a
      barrier of 22.71 kcal/mol. These predictions agree rather well with the MPW1K and
      BB1K density functional theory predictions but disagree with predictions based on
      B3LYP energies or geometries. Our RRKM/master equation simulations suggest that
      almost 50% of I undergoes a prompt hydrogen shift reaction at pressures up to 10
      Torr, but the extent to which I is chemically activated is uncertain. For
      Reaction 1 at 298 K, the variational TST rate constant is approximately 30% lower
      than the conventional TST result, and the microcanonical optimized
      multidimensional tunneling (muOMT) method predicts that tunneling accelerates the
      reaction by a factor of 3. TST calculations on Reaction 2 reveal no variational
      effect and a 298 K muOMT transmission coefficient of 10(5). The Eckart method
      overestimates transmission coefficients for both reactions.

PMID- 17508727
TI  - The extracellular region of the receptor for advanced glycation end products is
      composed of two independent structural units.
AB  - The receptor for advanced glycation end products (RAGE) is an important cell
      surface receptor being pursued as a therapeutic target because it has been
      implicated in complications arising from diabetes and chronic inflammatory
      conditions. RAGE is a single membrane spanning receptor containing a very small
      approximately 40 residue cytosolic domain and a large extracellular region
      composed of 3 Ig-like domains. In this study, high level bacterial expression
      systems and purification protocols were generated for the extracellular region of
      RAGE (sRAGE) and the five permutations of single and tandem domain constructs to
      enable biophysical and structural characterization of its tertiary and quaternary
      structure. The structure and stability of each of these six protein constructs
      was assayed by biochemical methods including limited proteolysis, dynamic light
      scattering, CD, and NMR. A homology model of sRAGE was constructed to aid in the
      interpretation of the experimental data. Our results show that the V and C1
      domains are not independent domains, but rather form an integrated structural
      unit. In contrast, C2 is attached to VC1 by a flexible linker and is fully
      independent. The interaction with a known RAGE ligand, Ca2+-S100B, was mapped to
      VC1, with the major contribution from the V domain but clearly defined secondary
      effects from the C1 domain. The implications of these results are discussed with
      respect to models for RAGE signaling.

PMID- 17508729
TI  - Single-particle light scattering: imaging and dynamical fluctuations in the
      polarization and spectral response.
AB  - A theoretical framework for light scattering from individual nanoscale particles
      or structures is developed. The main considerations distinguishing the present
      treatment from the theories developed for conventional light-scattering
      experiments are the experimental requirements for the detection of the limited
      light from a single scatterer. These requirements include use of a high numerical
      aperture microscope objective, annular illumination, and the reduced linear
      dichroism instead of depolarization ratio. It is shown how these issues are
      considered in relating the microscopic polarizability tensor to the far-field
      experimental observables. The approach is further extended to include the
      dynamical response in the scattering polarization and spectrum and discussed in
      the context of the particle's rotational diffusion. For dynamic light scattering,
      analytical expressions are derived to elucidate the interrelationship between the
      experimental configuration, the observable, the polarizability tensor, and the
      diffusion tensor. Specific examples including static imaging and dynamic
      correlation for rodlike and spheroidal scatterers are discussed to illustrate the
      application of the theory.

PMID- 17508731
TI  - Proteins in different Synechocystis compartments have distinguishing N-terminal
      features: a combined proteomics and multivariate sequence analysis.
AB  - Cyanobacteria have a cell envelope consisting of a plasma membrane, a periplasmic
      space with a peptidoglycan layer, and an outer membrane. A third, separate
      membrane system, the intracellular thylakoid membranes, is the site for both
      photosynthesis and respiration. All membranes and luminal spaces have unique
      protein compositions, which impose an intriguing mechanism for protein sorting of
      extracytoplasmic proteins due to single sets of translocation protein genes. It
      is shown here by multivariate sequence analyses of many experimentally identified
      proteins in Synechocystis, that proteins routed for the different extracytosolic
      compartments have correspondingly different physicochemical properties in their
      signal peptide and mature N-terminal segments. The full-length mature sequences
      contain less significant information. From these multivariate, N-terminal
      property-profile models for proteins with single experimental localization,
      proteins with ambiguous localization could, to a large extent, be predicted to a
      defined compartment. The sequence properties involve amino acids varying
      especially in volume and polarizability and at certain positions in the sequence
      segments, in a manner typical for the various compartment classes. Potential
      means of the cell to recognize the property features are discussed, involving the
      translocation channels and two Type I signal peptidases with different cellular
      localization, and charge features at their membrane interfaces.

PMID- 17508732
TI  - Amino acid sequence determination of protein biomarkers of Campylobacter
      upsaliensis and C. helveticus by "composite" sequence proteomic analysis.
AB  - We have identified the protein biomarkers observed in the matrix-assisted laser
      desorption/ionization time-of-flight mass spectra (MALDI-TOF-MS) of cell lysates
      of five strains of Campylobacter upsaliensis and one strain of C. helveticus by
      "bottom-up" proteomic techniques. Only one C. upsaliensis strain had previously
      been genomically sequenced. The significant findings are as follows: (1) The
      protein biomarkers identified were: 10 kD chaperonin, protein of unknown function
      (DUF465), phnA protein, probable periplasmic protein, D-methionine-binding
      lipoprotein MetQ, cytochrome c family protein, DNA-binding protein HU,
      thioredoxin, asparigenase family protein, helix-turn-helix domain protein, as
      well as several ribosomal and conserved hypothetical proteins. (2) Amino acid
      substitutions in protein biomarkers across species and strains account for
      variations in biomarker ion mass-to-charge (m/z). (3) The most common post
      translational modifications (PTMs) identified were cleavage of N-terminal
      methionine and N-terminal signal peptides. The rule that predicts N-terminal
      methionine cleavage, based on the penultimate residue, does not appear to apply
      to C. upsaliensis proteins when the penultimate residue is threonine. (4) It was
      discovered that some protein biomarker genes of the genomically sequenced C.
      upsaliensis strain were found to have nucleotide sequences with GTG or TTG
      "start" codons that were not the actual start codon (ATG) of the protein based on
      proteomic analysis. (5) Proteomic identification of the protein biomarkers of the
      non-genomically sequenced C. upsaliensis and C. helveticus strains involved
      identification of homologous protein amino acid sequences to that of the
      sequenced strain. Interestingly, some protein sequence regions that were not
      completely homologous to the sequenced strain, due to amino acid substitutions,
      were found to have homologous sequence regions from more phyogenetically distant
      species/strains, e.g., C. jejuni. Exploiting this partial homology of more
      distant species/strains, it was possible to construct a "composite" amino acid
      sequence using multiple non-overlapping sequence regions from both
      phylogenetically proximate and distant strains. The new composite sequence was
      confirmed by both MS and MS/MS data. Thus, it was possible in some cases to
      determine the amino acid sequence of an unknown protein biomarker from a
      genomically non-sequenced bacterial strain without the necessity of either
      genetically sequencing the biomarker gene or resorting to de novo MS/MS analysis
      of the full protein sequence.

PMID- 17508733
TI  - A multilayer model for self-propagating high-temperature synthesis of
      intermetallic compounds.
AB  - Self-propagating high-temperature synthesis of intermetallic compounds is of wide
      interest. We consider reactions in a binary system in which the rise and fall of
      the temperature during the reaction is such that one of the reacting metals melts
      but not the other. For such a system, using the phase diagram of the binary
      system, we present a general theory that describes the reaction taking place in a
      single solid particle of one component surrounded by the melt of the second
      component. The theory gives us a set of kinetic equations that describe the
      propagation of the phase interfaces in the solid particle and the change in
      composition of the melt that surrounds it. In this article, we derive a set of
      equations for one- and two-layer systems in which each layer is a binary compound
      in the phase diagram. The system of equations is numerically solved for Al-Ni to
      illustrate the applicability of the theory. The method presented here is general
      and, depending on the complexity of the phase diagram, it could be used to obtain
      similar equations for systems with more layers.

PMID- 17508734
TI  - The hydrolysis of amides and the proficiency of amidohydrolases. The burden borne
      by kw.
AB  - The hydrolysis of small amides has garnered major attention due to its relevance
      to peptide hydrolysis, one of the most fundamental reactions of biology. Both
      experimental and theoretical research efforts have studied the reaction in
      different media, and a consensus has been reached regarding the specific acid-
      and base-catalyzed reaction pathways. Nevertheless, for the water reaction, large
      discrepancies between theoretical and experimental results are found in the
      literature. Herein, we report the results of theoretical calculations of
      formamide and urea hydrolysis at different pH values. Model systems have been
      built clustering one and two water molecules with the reactive amide. A careful
      analysis of the reaction pathways at different temperatures has allowed us to
      accurately reproduce available experimental data and to separate the water
      reactions from their acid and base counterparts. The relevance of the results in
      providing an accurate definition of the proficiency of amidohydrolases is
      discussed.

PMID- 17508735
TI  - Noncovalent interactions between cytosine and SWCNT: curvature dependence of
      complexes via pi...pi stacking and cooperative CH...pi/NH...pi.
AB  - Fragments of C24H12, adapted from a variety of armchair [(n,n), (n = 5, 7, and
      8)] and zigzag [(m,0) (m = 8, 10, and 12)] single-walled carbon nanotube (SWCNT),
      are used to model corresponding SWCNTs with different diameters and electronic
      structures. The parallel binding mainly through pi...pi stacking interaction, as
      well as the perpendicular binding via cooperative NH...pi and CH...pi between
      cytosine and the fragments of SWCNT have been extensively investigated with a GGA
      type of DFT, PW91LYP/6-311++G(d,p). The eclipsed tangential (ET) conformation
      with respect to the six-membered ring of cytosine and the central ring of SWCNT
      fragments is less stable than the slipped tangential (ST) conformation for the
      given fragment; perpendicular conformations with NH2 and CH ends have higher
      negative binding energy than those with NH and CH ends. At PW91LYP/6-311++G(d,p)
      level, two tangential complexes are less bound than perpendicular complexes.
      However, as electron correlation is treated with MP2/6-311G(d,p) for PW91LYP/6
      311++G(d,p) optimized complexes, it turns out there is an opposite trend that two
      tangential complexes become more stable than three perpendicular complexes. This
      result implies that electron correlation, a primary source to dispersion energy,
      has more significant contributions to the pi...pi stacking complexes than to the
      complexes via cooperative NH...pi and CH...pi interactions. In addition, it was
      found for the first time that binding energies for two tangential complexes
      become more negative with increasing nanotube diameter, while those for three
      perpendicular complexes have a weaker dependence on the curvature; i.e., binding
      energies are slightly less and less negative. The performance of a novel hybrid
      DFT, MPWB1K, was also discussed.

PMID- 17508736
TI  - Static normal coordinate deformations of the heme group in mutants of
      ferrocytochrome c from Saccharomyces cerevisiae probed by resonance Raman
      spectroscopy.
AB  - The function of heme proteins is, to a significant extent, influenced by the
      ligand field probed by the heme iron, which itself can be affected by
      deformations of the heme macrocycle. The exploration of this field is difficult
      because the heme structure obtained from X-ray crystallography is not resolved
      enough to unambiguously identify structural changes on the scale of 10(-2) A.
      However, asymmetric deformations in this order of magnitude affect the
      depolarization ratio of the resonance Raman lines assignable to normal vibrations
      of the heme group. We have measured the dispersion of the depolarization ratios
      of four structure sensitive Raman bands (i.e., nu4, nu11, nu21, and nu28) in
      yeast iso-1-ferrocytochrome c and its mutants N52V, Y67F, and N52VY67F with B-
      and Q-band excitation. The DPR dispersion of all bands indicates the presence of
      asymmetric in-plane and out-of-plane deformations. The replacement of the polar
      tyrosine residue at position 67 by phenylalanine significantly increases the
      triclinic B2g deformation, which involves a distortion of the pyrrole symmetry.
      We relate this deformation to changes of the electronic structure of pyrrole A,
      which modulates the interaction between its propionate substituents and the
      protein environment. This specific heme deformation is eliminated in the double
      mutant N52VY67F. The additional substitution of N52 by valine induces a
      tetragonal B1g deformation which involves asymmetric changes of the Fe-N
      distances and increases the rhombicity of the ligand field probed by the heme
      iron. This heme deformation might be caused by the elimination of the water
      protein hydrogen-bonding network in the heme cavity. The single mutation N52V
      does not significantly perturb the heme symmetry, but a small B1g deformation is
      consistent with our data and the heme structure obtained from a 1 ns molecular
      dynamics simulation of the protein.

PMID- 17508737
TI  - Calculation of the free energy of polarization: quantifying the effect of
      explicitly treating electronic polarization on the transferability of force-field
      parameters.
AB  - The lack of an explicit description of electronic polarization in nonpolarizable
      force fields usually results in an incomplete transferability of force-field
      parameter sets when applied in simulations of the system of interest in either a
      polar or an apolar environment. For example, the use of nonpolarizable parameter
      sets optimized to reproduce experimental data on properties of pure liquids of
      polar compounds commonly yields too low solubilities in water for the
      corresponding compounds. The reason is that the fixed charge distributions
      calibrated for the pure liquid might correspond to too low molecular dipole
      moments in case of hydration. In the current study, we quantitatively show that
      explicit inclusion of electronic polarization can improve the transferability of
      biomolecular force-field parameter sets. With this aim, free energies of
      polarization, DeltaGpola, have been calculated, with DeltaGpola corresponding to
      the free energy difference between identical systems described by a polarizable
      and a nonpolarizable model. Using a nonpolarizable model and a polarizable one
      (based on the charge-on-spring approach) for dimethyl ether (DME), which were
      both parametrized to reproduce experimental values for pure liquid properties,
      small values were found for DeltaGpola for the pure liquid or when a DME solute
      was solvated in the apolar solvent cyclohexane. For the solute hydrated in water,
      however, DeltaGpola was found to be of the same order of magnitude as the
      discrepancy between the free energy of hydration from simulation using a
      nonpolarizable solute model and the experimental value. Thus, introducing
      polarizabilities clearly improves the transferability of the parameter set.
      Additionally, in calculations of an anion solvated in DME, DeltaGpola for the
      solvent adopted relatively large values. From an estimation of the errors in the
      calculated free energy differences, it was furthermore shown that the calculation
      of DeltaGpola offers an effective and accurate method to obtain differences in
      solvation (or excess) free energies between systems described by polarizable and
      nonpolarizable models when compared to a direct calculation of solvation (or
      excess) free energies.

PMID- 17508738
TI  - Influences of linkage stiffness on rupture rate in single-molecule pulling
      experiments.
AB  - In the dissociation of a noncovalent biomolecular bond by external pulling, the
      bonded site is often connected to the force-acting site by a linkage. The role of
      the linkage stiffness on the rupture of a ligand-receptor complex under constant
      force is investigated by overdamped Langevin dynamics for the elastically coupled
      ligand and probe. The effects on the bond lifetime include effective ligand
      diffusivity, force fluctuations, and violation of adiabatic condition. The
      rupture rate declines with increasing linkage stiffness. For soft linkage, the
      effect associated with the spring and probe can be ignored, and the true rupture
      rate can be extracted. On the other hand, for stiff linkage, the diffusivity of
      the probe has to be accounted for and, thus, leads to a lower rupture rate,
      depending on the diffusivity ratio between the probe and ligand. Nevertheless,
      the energy barrier height can be reasonably extracted by constant pulling
      experiments, regardless of the linkage stiffness.

PMID- 17508739
TI  - Accurate description of nitrogenous base flexibility in classical molecular
      dynamics simulations of nucleotides bound to proteins.
AB  - Proteins can induce significant distortions in planar cyclic compounds upon
      binding, in particular in nucleotide-enzyme complexes. An accurate representation
      of the ring flexibility is thus desirable when modeling these systems through
      classical force fields, especially when deformations are supposed to be involved
      in the catalytic mechanism. In this study, we use a newly developed general
      procedure to determine sets of dihedral parameters for planar cycles that
      accurately reproduce their out-of-plane normal modes as determined at the quantum
      mechanical (QM) level. The optimization allows the deviation from reference data
      to be reduced for the pyrimidine bases to values comparable to the accuracy of
      the QM data. Furthermore, the influence of the description of ring flexibility in
      protein-ligand interactions is assessed through molecular dynamics simulations of
      the complex between uridine and the pyrimidine-specific nucleoside hydrolase YeiK
      using the AMBER force field. The differences in ligand-protein interactions
      emerging from different parameter sets are also discussed with respect to
      existing biochemical data.

PMID- 17508740
TI  - Computational clues for a new mechanism in the glycosylase activity of the human
      DNA repair protein hOGG1. A generalized paradigm for purine-repairing systems?
AB  - A theoretical density functional theory (DFT, B3LYP) investigation has been
      carried out on the catalytic cycle responsible for the glycosylase activity of
      the human DNA repair protein hOGG1: enzyme activation, cleavage of the glycosidic
      bond, and expulsion of the damaged base. An unprecedented large quantum mechanics
      (QM) model system has been used, which includes a complete oxoG molecule, the
      deoxyribose ring bonded to the phosphate groups, and most of the surrounding
      residues that simulate the protein binding pocket. It has been found that Asp268
      does not play any role in Lys249 activation and that the oxoG basis acts as a
      coenzyme, triggering nucleophile activation by Lys249 deprotonation. An SN2
      nucleophilic attack by Lys249 on the anomeric carbon then follows. This is the
      rate-determining step of the process with an activation barrier of 16.7 kcal mol(
      1) in good agreement with the experimental value of 17.1 kcal mol(-1). The
      expelled oxoG plays again as an enzyme cofactor at the end of the process by
      activating (via proton transfer) ribose ring opening and Schiff base formation.
      This study suggests a recurring catalytic strategy in the enzymatic cleavage of
      purine nucleoside where the activation of the leaving group by protonation of the
      nucleoside base (via an enzymatic general acid) triggers the cleavage of the
      glycosidic bond.

PMID- 17508741
TI  - Prepared chiral nanorods of a cobalt(II) porphyrin dimer and studied changes of
      UV-Vis and CD spectra with aggregate morphologies under different temperatures.
AB  - Novel porphyrin dimer ligand and cobalt complexes by directly bridging with l
      glutamic acid have been prepared and characterized. The intensities of circular
      dichroism and UV-vis spectra that change the aggregate morphologies of the
      porphyrin dimer under different temperatures have been investigated.

PMID- 17508742
TI  - Origin of the zero-field splitting in mononuclear octahedral dihalide MnII
      complexes: an investigation by multifrequency high-field electron paramagnetic
      resonance and density functional theory.
AB  - The synthesis, structural characterization, and electronic properties of a new
      series of high-spin six-coordinate dihalide mononuclear MnII complexes
      [Mn(tpa)X2] (tpa=tris-2-picolylamine; X=I (1), Br (2), and Cl (3)) are reported.
      The analysis of the crystallographic data shows that in all investigated
      complexes the manganese ion lies in the center of a distorted octahedron with a
      cis configuration of the halides imposed by the tpa ligand. By a multifrequency
      high-field electron paramagnetic resonance investigation (95-285 GHz), the
      electronic properties of 1-3 were determined (DI=-0.600, DBr=-0.360, DCl=+0.115
      cm-1), revealing the important effect of (i) the nature of the halide and (ii)
      the configuration (cis/trans) of the two halides on the magnitude of D. The spin
      Hamiltonian parameters obtained by density functional theory calculations
      initiated from the crystal structure of 1-3 are in reasonable agreement with the
      experimental values. The absolute value of D is consistently overestimated, but
      the sign and the trend over the chemical series is well reproduced. Theoretical
      models (cis- and trans-[Mn(NH3)4X2], X=I, Br, Cl and F) have been used to
      investigate the different contributions to D and also to understand the origin of
      the experimentally observed changes in D within the series reported here. This
      study reveals that the spin-spin coupling contributions to the D tensor are non
      negligible for the lighter halides (F, Cl) but become insignificant for the
      heavier halides (I, Br). The four different types of excitations involved in the
      spin-orbit coupling (SOC) part of the D tensor contribute with comparable
      magnitudes and opposing signs. The general trend observed for halide MnII
      complexes (DI>DBr>DCl) can be explained by the fact that the halide SOC dominates
      the D value in these systems with a major contribution arising from interference
      between metal- and halide-SOC contributions, which are proportional to the
      product of the SOC constants of Mn and X.

PMID- 17508743
TI  - Zinc-porphyrin phosphonate coordination: structural control through a zinc
      phosphoryl-oxygen interaction.
AB  - Inter- and intramolecular zinc-porphyrin phosphonate coordination in the cis and
      trans isomers of zinc tetraphenylporphyrinstyryldiphosphonate is reported,
      demonstrating the potential of the zinc phosphoryl-oxygen interaction for
      structural control.

PMID- 17508745
TI  - Palladium(0)-catalyzed trimerization of arylisocyanates into 1,3,5
      triarylisocyanurates in the presence of diimines: a nonintuitive mechanism.
AB  - We show here that palladium(0) (dibenzylideneacetone) complexes bearing 1,10
      phenanthroline constitute efficient catalysts for the cyclotrimerization of
      aromatic isocyanates. For the first time, the mechanism of this reaction has been
      investigated experimentally and theoretically with group 10 catalysts. This
      investigation provides a very consistent picture of the catalytic cycle. Notably,
      we establish that the reaction does not proceed by stepwise cycloadditions or
      ring insertions involving metallacyclic intermediates, as might have been
      anticipated. Rather, in our proposal, the initial steps of the mechanism resemble
      the chain-growth process operative during the anionic polymerization of
      isocyanates and feature charge-separated intermediates. These steps are then
      followed by ring closure on the metal center of the last intermediate formed to
      yield a seven-membered metallacycle that reductively eliminates the cyclotrimer
      and re-forms the active species. In addition, we conclusively show that the
      (known) palladacycles that could be isolated during the experimental
      investigations are not catalytic intermediates but result from catalyst
      deactivation. Thus, with Pd(0) diimine catalysts, the actual trimerization
      mechanism appears to be a blend between the two types of mechanisms proposed thus
      far for the oligomerization of heterocumulenes with very different catalysts. In
      conclusion, this work contributes to a better understanding of the reactivity of
      arylisocyanates in the vicinity of late group 10 metal centers in low oxidation
      state and sheds some light on the detrimental self-poisoning processes observed
      during the reductive carbonylation of nitroaromatic substrates catalyzed by
      related catalysts in non-nucleophilic media.

PMID- 17508746
TI  - Two classes of alongside charge-transfer interactions defined in one [2]catenane.
AB  - A [2]catenane, which incorporates hydroquinone (HQ) and a sterically bulky
      tetrathiafulvalene (TTF) into a bismacrocycle, has been designed to probe the
      alongside charge-transfer (CT) interactions taking place between a TTF unit and
      one of the bipyridinium moieties in the tetracationic cyclophane
      cyclobis(paraquat-p-phenylene) (CBPQT4+). A template-directed strategy employs
      the HQ unit as the primary template for formation of the tetracationic cyclophane
      CBPQT4+, affording the desired [2]catenane structure but as an uncharacteristic
      green solid. The X-ray crystal structure and detailed 13C NMR assignments have
      identified a stereoselective preference for catenation about the cis isomer. The
      1H NMR spectroscopy, electrochemistry, and X-ray crystallography all confirm that
      the CBPQT4+ cyclophane encircles the HQ unit, thereby defining a structure which
      would normally determine a red color. The visible-NIR region of the absorption
      spectrum displays a band at approximately 740 nm that is unambiguously assigned
      to a TTF --> CBPQT4+ CT transition on the basis of resonance Raman spectroscopy
      using 785 nm excitation. The profile of the CT band changes depending on the
      ratio of the cis- to trans-TTF isomers in the [2]catenane for which the molar
      absorptivity of each isomer is estimated to be significantly different at epsilon
      max = 380 and 3690 M-1 cm-1, respectively. Molecular modeling studies confirmed
      that the observed difference in the absorption spectroscopic profile can be
      accounted for by both a better overlap of the HOMO(TTF) and LUMO+1(CBPQT4+) as
      well as a more stable face-to-face (pi...pi) conformation in the trans isomer
      compared to the edge-to-face cis isomer of the [2]catenane. The latter is
      arranged for pi-orbital overlap through the sulfur atoms of the TTF unit, thereby
      defining an [Spi...pi] interaction.

PMID- 17508747
TI  - A magnetism-assisted chemical vapor deposition method to produce branched or iron
      encapsulated carbon nanotubes.
AB  - A magnetism-assisted chemical vapor deposition method was developed to synthesize
      branched or iron-encapsulated carbon nanotubes. In the process, the external
      magnetic field can promote the coalescence or division of the catalyst particles,
      causing the formation of branched or encapsulated nanostructures. This finding
      will extend the understanding of the chemical vapor deposition method in a
      magnetic field and promote the applications of branched or encapsulated
      nanostructures.

PMID- 17508748
TI  - Metastable water clusters in the nonpolar cavities of the thermostable protein
      tetrabrachion.
AB  - Water expulsion from the protein core is a key step in protein folding.
      Nevertheless, unusually large water clusters confined into the nonpolar cavities
      have been observed in the X-ray crystal structures of tetrabrachion, a bacterial
      protein that is thermostable up to at least 403 K (130 degrees C). Here, we use
      molecular dynamics (MD) simulations to investigate the structure and
      thermodynamics of water filling the largest cavity of the right-handed coiled
      coil stalk of tetrabrachion at 365 K (92 degrees C), the temperature of optimal
      bacterial growth, and at room temperature (298 K). Hydrogen-bonded water clusters
      of seven to nine water molecules are found to be thermodynamically stable in this
      cavity at both temperatures, confirming the X-ray studies. Stability, as measured
      by the transfer free energy of the optimal size cluster, decreases with
      increasing temperature. Water filling is thus driven by the energy of transfer
      and opposed by the transfer entropy, both depending only weakly on temperature.
      Our calculations suggest that cluster formation becomes unfavorable at
      approximately 384 K (110 degrees C), signaling the onset of drying just slightly
      above the temperature of optimal growth. "Drying" thus precedes protein
      denaturation. At room temperature, the second largest cavity in tetrabrachion
      accommodates a five water molecule cluster, as reported in the X-ray studies.
      However, the simulations show that at 365 K the cluster is unstable and breaks
      up. We suggest that the large hydrophobic cavities may act as binding sites for
      two proteases, possibly explaining the unusual thermostability of the resulting
      protease-stalk complexes (up to approximately 393 K, 120 degrees C).

PMID- 17508749
TI  - Switching from S- to R-selectivity in the Candida antarctica lipase B-catalyzed
      ring-opening of omega-methylated lactones: tuning polymerizations by ring size.
AB  - Novozym 435-catalyzed ring-opening of a range of omega-methylated lactones
      demonstrates fascinating differences in rate of reaction and enantioselectivity.
      A switch from S- to R-selectivity was observed upon going from small (ring sizes
      <or=7) to large lactones (ring sizes >or=8). This was attributed to the
      transition from a cisoid to a transoid conformational preference of the ester
      bond on going from small to large lactones. The S-selectivity of the ring-opening
      of the small, cisoid lactones was low to moderate, while the R-selectivity of the
      ring-opening of the large transoid lactones was surprisingly high. The S
      selectivity of the ring-opening of the small, cisoid lactones combined with the
      established R-selectivity of the transesterification of (aliphatic) secondary
      alcohols prevented polymerization from taking place. Ring-opening of the large,
      transoid lactones was R-selective with high enantioselectivity. As a result,
      these lactones could be polymerized, without exception, by straightforward
      kinetic resolution polymerization, yielding the enantiopure R-polyester with
      excellent enantiomeric excess (>99%).

PMID- 17508750
TI  - Triplet reactivity and regio-/stereoselectivity in the macrocyclization of
      diastereomeric ketoprofen-quencher conjugates via remote hydrogen abstractions.
AB  - Intramolecular excited triplet state interactions in diastereomeric compounds
      composed of a benzophenone chromophore (ketoprofen) and various hydrogen donor
      moieties (tetrahydrofuran, isopropylbenzene) have been investigated by laser
      flash photolysis. The rate constants for hydrogen abstraction by excited triplet
      benzophenone are in the order of 10(4)-10(5) s(-1), with the highest reactivity
      for the tetrahydrofuran residue. A remarkable diastereodifferentiation, expressed
      in the triplet lifetimes of the carbonyl chromophore (e.g., 1.6 versus 2.7
      micros), has been found for these compounds. With an alkylaromatic moiety as
      donor, related effects have been observed, albeit strongly dependent on the
      length of the spacer. The reactivity trend for the initial hydrogen transfer step
      is paralleled by the quantum yields of the overall photoreaction. The biradicals,
      formed via remote hydrogen abstraction, undergo intramolecular recombination to
      macrocyclic ring systems. The new photoproducts have been isolated and
      characterized by NMR spectroscopy. The stereochemistry of the macrocycles, which
      contain up to four asymmetric carbons, has been unambiguously assigned on the
      basis of single-crystal structures and/or NOE effects. Interestingly, a highly
      regio- and stereoselective macrocyclization has been found for the ketoprofen
      tetrahydrofuran conjugates, where hydrogen abstraction from the less substituted
      carbon is exclusive; cisoid ring junction is always preferred over the transoid
      junction. The photoreaction is less regioselective for compounds with an
      isopropylbenzene residue. The reactivity and selectivity trends have been
      rationalized by DFT (B3LYP/6-31G*) calculations.

PMID- 17508751
TI  - Tuning of redox properties of iron and iron oxides via encapsulation within
      carbon nanotubes.
AB  - We report the tuning of the redox properties of iron and iron oxide nanoparticles
      by encapsulation within carbon nanotubes (CNTs) with varying inner diameters.
      Raman spectroscopy was employed to investigate the interaction of the
      encapsulated nanoparticles with the CNTs. A red shift of the Fe-O mode is
      observed in the nanoparticles deposited on the outer CNT surfaces with respect to
      bulk Fe2O3. However, this mode is found to be stepwise blue-shifted with
      decreasing inner diameter in the CNT-encapsulated Fe2O3 nanoparticles, suggesting
      an enhanced interaction of Fe2O3 with the inner CNT surface as its curvature
      increases. The autoreduction of the encapsulated Fe2O3 is significantly
      facilitated inside CNTs with respect to the outside nanoparticles. Interestingly,
      it becomes more facile with decreasing CNT channel diameter as evidenced by
      temperature programmed reaction, in situ XRD, and Raman spectroscopy. The
      oxidation of encapsulated metallic Fe nanoparticles on the other hand is retarded
      in comparison to that of the outside Fe particles as shown by in situ XRD and
      gravimetrical measurements with an online microbalance. We attribute this tunable
      redox behavior of transition metal nanoparticles inside CNTs to a particular
      electronic interaction of the encapsulates with the interior CNT surface, which
      stabilizes the metallic state of Fe.

PMID- 17508752
TI  - A high-mobility electron-transport polymer with broad absorption and its use in
      field-effect transistors and all-polymer solar cells.

PMID- 17508753
TI  - Asymmetric amine-intercepted Nazarov cyclization.

PMID- 17508754
TI  - A fluorescence turn-on mechanism to detect high explosives RDX and PETN.

PMID- 17508755
TI  - An isolable silanoic ester by oxygenation of a stable silylene.

PMID- 17508756
TI  - Effect of thickeners on aroma compound behavior in a model dairy gel.
AB  - The effects of thickeners on the headspace release of aroma compounds from a
      model dairy gel were investigated. Starch, pectin, and locust bean gum (LBG) were
      introduced separately to the fat-free dairy gel via sugar syrups. The release of
      nine aroma compounds was analyzed by solid-phase microextraction (SPME), and the
      partition coefficients of retention were calculated. For an increase in starch
      concentration, there was an overall decrease in aroma release. Pectin
      concentrations in gel higher than 0.04% caused an increase in aroma release. For
      LBG no major effect was observed. A quantitative structure-property relationship
      (QSPR) approach was used to propose which types of interactions were involved
      between aroma molecules and thickener macromolecules in the complex foodstuff.
      Twenty molecular descriptors of volatile compounds appeared to be significant in
      correlation with the partition coefficients of retention. The surface-weighted
      negatively charged partial surface area seemed to play a critical role in the
      behavior of aroma compound.

PMID- 17508757
TI  - Development of a certified reference material for genetically modified potato
      with altered starch composition.
AB  - The presence of genetically modified organisms (GMOs) in food and feed products
      is subject to regulation in the European Union (EU) and elsewhere. As part of the
      EU authorization procedure for GMOs intended for food and feed use, reference
      materials must be produced for the quality control of measurements to quantify
      the GMOs. Certified reference materials (CRMs) are available for a range of
      herbicide- and insect-resistant genetically modified crops such as corn, soybean,
      and cotton. Here the development of the first CRM for a GMO that differs from its
      non-GMO counterpart in a major compositional constituent, that is, starch, is
      described. It is shown that the modification of the starch composition of potato
      (Solanum tuberosum L.) tubers, together with other characteristics of the
      delivered materials, have important consequences for the certification strategy.
      Moreover, the processing and characterization of the EH92-527-1 potato material
      required both new and modified procedures, different from those used routinely
      for CRMs produced from genetically modified seeds.

PMID- 17508758
TI  - Validation of antifreeze properties of glutathione based on its thermodynamic
      characteristics and protection of baker's yeast during cryopreservation.
AB  - The antifreeze ability of glutathione was evaluated on the basis of its
      thermodynamic characteristics and protection of baker's yeast during
      cryopreservation at -30 degrees C. The thermodynamic characteristics and
      protection of baker's yeast of glutathione were similar to those of known
      antifreeze proteins, such as carrot antifreeze protein and holly antifreeze
      protein. These properties included lowering the freezing point at about 0.20
      degrees C non-colligatively, decreasing freezable water content, controlling the
      movement of free water for its strong hydrophilicity, and improving baker's yeast
      survival during the simulated processing of frozen dough. Therefore, glutathione
      was viewed to be an antifreeze protein like substance on the basis of its unique
      thermodynamic characteristics and protection of baker's yeast. The method
      combining thermodynamic characteristic analysis and protection evaluation is a
      new and simple way to screen new antifreeze proteins.

PMID- 17508760
TI  - Synthesis of the tricyclic core of colchicine via a dienyne tandem ring-closing
      metathesis reaction.
AB  - The synthesis of the tricyclic framework of colchicine has been achieved using a
      tandem ring-closing metathesis reaction of dienynes as the key step. In this
      process, both seven-membered rings B and C were formed in one step. Oxidation of
      tertiary allylic alcohol derived from the tandem metathesis product furnished an
      intermediate in the total synthesis of colchicine.

PMID- 17508759
TI  - Tautomeric modification of GlcNAc-thiazoline.
AB  - The potent O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline has been modified by
      buffer- or acylation-induced imine-to-enamine conversion and then electrophile or
      radical addition (Xn = D3, F, N3, OH, SMe, COCF3, CF3). Several functionalized
      GlcNAc-thiazolines show highly selective inhibition of OGA vs human
      hexosaminidase and thus have promise as tools for targeted investigations of OGA,
      an enzyme linked to diabetes and neurodegeneration. A new radical
      addition/fragmentation reaction of the N-(trifluoroacetyl)enamine has been
      discovered.

PMID- 17508761
TI  - Nitro-substituted stilbeneboronate pinacol esters and their fluoro-adducts.
      Fluoride ion induced polarity enhancement of arylboronate esters.
AB  - A series of stilbeneboronate pinacol cyclic esters, containing none to three
      nitro groups, have been synthesized by various olefination reactions and
      characterized by X-ray single-crystal structure analysis. A stilbeneboronate
      ester bearing electron-acceptor groups experiences transition to a push-pull pi
      electron system upon complexation with one fluoride ion at the boron atom. The UV
      vis absorption maxima of the presented nitro-substituted stilbeneboronate esters
      are red-shifted upon addition of fluoride ions, indicating this binding event.
      The enhancement of the polarity of the investigated compounds and the changes in
      the electronic system were investigated by UV-vis absorption spectroscopy and
      solvatochromism. Additionally, studies were performed by natural bond orbital
      (NBO) analysis and RI-CC2 calculations of the vertical excitation energies. The
      synergism of fluoride ion complexation and solvation upon the UV-vis band shift
      is interpreted in terms of linear solvation energy relationships (LSERs) using
      the Kamlet-Taft solvent parameter set. It is found that the UV-vis absorption of
      the fluoro-boronates is strongly dependent on the solvents hydrogen-bond donating
      ability.

PMID- 17508762
TI  - Thermal [2+2] cycloaddition of allenynes: easy construction of bicyclo[6.2.0]deca
      1,8-dienes, bicyclo[5.2.0]nona-1,7-dienes, and bicyclo[4.2.0]octa-1,6-dienes.
AB  - The simple refluxing of allenynes, having a phenylsulfonyl functionality on the
      allenyl group, in xylene (or mesitylene) without microwave irradiation resulted
      in the efficient formation of bicyclo[5.2.0]nona-1,7-dienes and
      bicyclo[4.2.0]octa-1,6-dienes in high yields. This method was shown to be
      successfully applicable to the first construction of bicyclo[6.2.0]deca-1,8
      dienes. Construction of the corresponding oxa- and azabicyclo[m.2.0] frameworks
      could also be attained. This thermal ring-closing reaction involves the formal
      [2+2] cycloaddition in which the distal double bond of an allenyl moiety
      exclusively served as one of the pi-components regardless of the position of the
      phenysulfonyl functionality on the allenyl moiety.

PMID- 17508763
TI  - Total synthesis of the cyclopeptide alkaloid abyssenine A. Application of inter-
      and intramolecular copper-mediated coupling reactions in organic synthesis.
AB  - The first total synthesis of the 15-membered ring cyclopeptide alkaloid
      abyssenine A 1 has been achieved with a longest linear sequence of 15 steps.
      Central to the synthetic approach was an efficient copper-mediated Ullmann
      coupling/Claisen rearrangement sequence allowing for both ipso and ortho
      functionalization of aromatic iodide 4. This sequence was used for the synthesis
      of the aromatic core. The synthetic utility of copper-catalyzed coupling
      reactions was further demonstrated to install the enamide with a concomitant
      straightforward macrocyclization starting from acyclic alpha-amido-omega-vinyl
      iodide 13.

PMID- 17508764
TI  - Dynamics of fibronectin adsorption on TiO2 surfaces.
AB  - In the present work we analyze the dynamics of fibronectin (FN) adsorption on two
      different stable titanium oxides, with varied surface roughness, and chemically
      similar to those used in clinical practice. The two types of titanium oxide
      surfaces used were TiO2 sputtered on Si (TiO2 sp) and TiO2 formed on commercially
      pure titanium after immersion in H2O2 (TiO2 cp). Surface characterization was
      previously carried out using different techniques (Sousa, S. R.; Moradas
      Ferreira, P.; Melo, L. V.; Saramago, B.; Barbosa, M. A. Langmuir 2004, 20 (22),
      9745-9754). Imaging and roughness analysis before and after FN adsorption used
      atomic force microscopy (AFM) in tapping mode, in air, and in magnetic
      alternating current mode, in liquid (water). FN adsorption as a function of time
      was followed by X-ray photoelectron spectroscopy (XPS), by radiolabeling of FN
      with 125I (125I-FN), and by ellipsometry. Exchangeability studies were performed
      using FN and HSA. AFM roughness analysis revealed that, before FN adsorption,
      both TiO2 surfaces exhibited a lower root-mean-square (Rq) and maximum peak with
      the depth of the maximum valley (Rmax) roughness in air than in water, due to
      TiO2 hydration. After protein adsorption, the same behavior was observed for the
      TiO2 sp substrate, while Rq and Rmax roughness values in air and in water were
      similar in the case of the TiO2 cp substrate, for the higher FN concentration
      used. Surface roughness was always significantly higher on the TiO2 cp surfaces.
      AFM led to direct visualization of adsorbed FN on both surfaces tested,
      indicating that after 10 min of FN incubation the TiO2 sp surface was partially
      covered by FN. The adsorbed protein seems to form globular aggregates or
      ellipsoids, and FN aggregates coalesce, forming clusters as the time of
      adsorption and the concentration increase. Radiolabeling of FN revealed that a
      rapid adsorption occurs on both surfaces and the amount adsorbed increased with
      time, reaching a maximum after 60 min of incubation. Time dependence is also
      observed for the evolution of the atomic (%) of N determined by XPS and by the
      increase of the thickness by ellipsometry. TiO2 cp adsorbs more FN than the TiO2
      sp surfaces, after 60 min of adsorption, as shown by the radiolabeling data. FN
      molecules are also more strongly attached to the former surface as indicated by
      the exchangeability studies. The overall results provide novel evidence that FN
      spontaneously adsorbs as a self-assembly at TiO2 surfaces as a function of time.
      The aggregate structure is an intermediate feature shared by some protein
      fibrillar assemblies at interfaces, which is believed to promote cell adhesion
      and cytoskeleton organization (Pellenc, D.; Berry, H.; Gallet, O. J. Colloid
      Interface Sci. 2006, 298 (1), 132-144. Maheshwari, G.; Brown, G.; Lauffenburger,
      D. A.; Wells, A.; Griffith, L. G. J. Cell Sci. 2000, 113 (10), 1677-1686).

PMID- 17508765
TI  - Nanoparticle films as electrodes: voltammetric sensitivity to the nanoparticle
      energy gap.
AB  - Electron-transfer reactions of redox solutes at electrode/solution interfaces are
      facilitated when their formal potentials match, or are close to, the energy of an
      electronic state of the electrode. Metal electrodes have a continuum of
      electronic levels, and redox reactions occur without restraint over a wide span
      of electrode potentials. This paper shows that reactions on electrodes composed
      of films of metal nanoparticles do have constraints when the nanoparticles are
      sufficiently small and molecule-like so as to exhibit energy gaps, and resist
      electron transfers with redox solutes at potentials within the energy gap. When
      solute formal potentials are near the electronic states of the nanoparticles in
      the film, electron-transfer reactions can occur. The electronic states of the
      nanoparticle film electrodes are reflected in the formal potentials of the
      electrochemical reactions of the dissolved nanoparticles at naked metal
      electrodes. These ideas are demonstrated by voltammetry of aqueous solutions of
      the redox solutes methyl viologen, ruthenium hexammine, and two ferrocene
      derivatives at films on electrodes of 1.1 nm core diameter Au nanoparticles
      coated with protecting monolayers of phenylethanethiolate ligands. The methyl
      viologen solute is unreactive at the nanoparticle film electrode, having a formal
      potential lying in the nanoparticle's energy gap. The other solutes exhibit
      electron transfers, albeit slowed by the electron hopping resistance of the
      nanoparticle film. The nanoparticles are not linked together, being insoluble in
      the aqueous medium; a small amount of an organic additive (acetonitrile)
      facilitates observing the redox solute voltammetry.

PMID- 17508766
TI  - Adsorption of dicarboxylic acids by clay minerals as examined by in situ ATR-FTIR
      and ex situ DRIFT.
AB  - The adsorption of dicarboxylic acids by kaolinite and montmorillonite at
      different pH conditions was investigated using in situ attenuated total
      reflectance Fourier transform infrared (ATR-FTIR) and ex situ diffuse reflectance
      infrared Fourier transform (DRIFT) spectroscopy. The sorption capacity of
      montmorillonite was greater than that of kaolinite. Adsorption of dicarboxylic
      acids (succinic acid, glutaric acid, adipic acid, and azelaic acid) was the
      highest at pH 4 as compared with those at pH 7 and 9. These results indicate that
      sorption is highly pH-dependent and related to the surface characteristics of
      minerals. The aliphatic chain length of the dicarboxylic acids highly influenced
      the sorption amount at acidic pH, regardless of the clay mineral species:
      succinic acid [HOOC(CH2)2COOH] < glutaric acid [HOOC(CH2)3COOH] < adipic acid
      [HOOC(CH2)4COOH] < azelaic acid [HOOC(CH2)7COOH]. With in situ ATR-FTIR analysis,
      most samples tend to have outer-sphere adsorption with the mineral surfaces at
      all tested pHs. However, inner-sphere coordination between the carboxyl groups
      and mineral surfaces at pH 4 was dominant from DRIFT analysis with freeze-dried
      complex samples. The complexation types, inner- or outer-sphere, depended on
      dicarboxylic acid species, pH, mineral surfaces, and solvent conditions. From the
      experimental data, we suggest that organic acids in an aqueous environment prefer
      to adsorb onto the test minerals by outer-sphere complexation, but inner-sphere
      complexation is favored under dry conditions. Thus, organic acid binding onto
      clay minerals under dry conditions is stronger than that under wet conditions,
      and we expect different conformations and aggregations of sorbed organic acids as
      influenced by complexation types. In the environment, natural organic material
      (NOM) may adsorb predominantly on positively charged mineral surfaces at the
      aqueous interface, which can convert into inner-sphere coordination during
      dehydration. The stable NOM/mineral complexes formed by frequent wetting-drying
      cycles in nature may resist chemical/microbial degradation of the NOM, which will
      affect carbon storage in the environment and influence the sorption of organic
      contaminants.

PMID- 17508767
TI  - Effect of agents modifying the membrane dipole potential on properties of
      syringomycin E channels.
AB  - We evaluated the effect of agents modifying the membrane dipole potential:
      phloretin, 6-ketocholestanol and RH 421 on the properties of single channels
      formed by lipodepsipeptide syringomycin E (SRE) in planar lipid bilayers. SRE
      forms two conductive states in lipid bilayers: "small" and "large." Large SRE
      channels are clusters of several small ones, demonstrating synchronous openings
      and closures. The increase in the membrane dipole potential led to (i) an
      increase in SRE channel conductance, (ii) an increase in the channel's lifetime,
      and (iii) a decrease in a number of synchronously operating small channels in the
      clusters. Overall, the results support the model of the small SRE channel
      synchronization in the cluster as voltage-dependent orientation of the lipid
      dipoles associated with the channel pores.

PMID- 17508768
TI  - Band gap and density of states of the hydrated C60 fullerene system at finite
      temperature.
AB  - We examine the electronic properties of the hydrated C60 fullerene under ambient
      conditions using a sequential Monte Carlo/density functional theory scheme. In
      this procedure, the average electronic properties of the first hydration shell of
      C60 equilibrate for ca. 40 uncorrelated configurations of the fullerene aqueous
      solution. We obtain a systematic red-shift of 0.8 eV in the band gap of the
      hydrated system, which is mainly attributed to the thermal fluctuations of the
      aqueous environment.

PMID- 17508769
TI  - Direct observation of the structural component of the metal-insulator phase
      transition and growth habits of epitaxially grown VO2 nanowires.
AB  - We have grown epitaxially orientation-controlled monoclinic VO2 nanowires without
      employing catalysts by a vapor-phase transport process. Electron microscopy
      results reveal that single crystalline VO2 nanowires having a [100] growth
      direction grow laterally on the basal c plane and out of the basal r and a planes
      of sapphire, exhibiting triangular and rectangular cross sections, respectively.
      In addition, we have directly observed the structural phase transition of single
      crystalline VO2 nanowires between the monoclinic and tetragonal phases which
      exhibit insulating and metallic properties, respectively, and clearly analyzed
      their corresponding relationships using in situ transmission electron microscopy.

PMID- 17508770
TI  - Bound excitons in metallic single-walled carbon nanotubes.
AB  - We extend previous ab initio calculations on excitonic effects in metallic single
      walled carbon nanotubes to more experimentally realizable larger diameter tubes.
      Our calculations predict bound exciton states in both the (10,10) and (12,0)
      tubes with binding energies of approximately 50 meV providing experimentally
      verifiable changes to the absorption line shape in each case. The second and
      third van Hove singularities in the joint density of states also give rise to a
      single optically active bound or resonant excitonic state.

PMID- 17508771
TI  - Transition of single-walled carbon nanotubes from metallic to semiconducting in
      field-effect transistors by hydrogen plasma treatment.
AB  - We report hydrogen plasma treatment results on converting the metallic single
      walled carbon nanotubes to semiconducting single-walled carbon nanotubes. We
      found that the as-grown single-walled carbon nanotubes (SWNTs) can be sorted as
      three groups which behave as metallic, as-metallic, and semiconducting SWNTs.
      These three groups have different changes under hydrogen plasma treatment and
      successive annealing process. The SWNTs can be easily hydrogenated in the
      hydrogen plasma environment and the as-metallic SWNTs can be transformed to
      semiconducting SWNTs. The successive annealing process can break the C-H bond, so
      the conversion is reversible.

PMID- 17508772
TI  - Determination of transport properties in chromium disilicide nanowires via
      combined thermoelectric and structural characterizations.
AB  - The Seebeck coefficient, electrical conductivity, and thermal conductivity of
      individual chromium disilicide nanowires were characterized using a suspended
      microdevice and correlated with the crystal structure and growth direction
      obtained by transmission electron microscopy on the same nanowires. The obtained
      thermoelectric figure of merit of the nanowires was comparable to the bulk
      values. We show that combined Seebeck coefficient and electrical conductivity
      measurements provide an effective approach to probing the Fermi Level, carrier
      concentration and mobility in nanowires.

PMID- 17508773
TI  - Virtual screening, molecular interaction field, molecular dynamics, docking,
      density functional, and ADMET properties of novel AChE inhibitors in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) affects approximately 10% of the world's population with
      65 years of age, being the most common form of dementia in adults and is
      characterized by senile plaquets and cholinergic deficits. Many drugs currently
      used for the treatment of the AD are based on the improvement of cholinergic
      neurotransmission achieved by Acetylcholinesterase (AChE) inhibition, the enzyme
      responsible for acetylcholine hydrolysis. We have focused in this work on the
      usage of computer-aided molecular design by virtual screening, molecular dynamics
      with implicit and explicit water solvation, density functional, molecular
      interaction field studies, docking procedures, ADMET predictions in order to
      propose novel potential AChE inhibitor for the treatment of Alzheimer's disease.

PMID- 17508774
TI  - Molecular dynamics study of intrinsic stability in six RNA terminal loop motifs.
AB  - Single stranded RNA molecules can assume a wide range of tertiary structures
      beyond the canonical A-form double helix. Certain sequences, termed motifs, are
      more common than a random distribution would suggest. The existence of such
      motifs can be rationalized in structural terms. In this study, we have
      investigated the intrinsic structural stability of RNA terminal loop motifs using
      multiple MD simulations in explicit water. Representative loops were chosen from
      the major tetraloop motifs, including also the U-turn motif. Not all loops retain
      their folded starting structure, but lowering the temperature to 277 K, or adding
      adjacent base pairs from the stem to which the motif is attached, helps
      stabilizing the folded loop structure.

PMID- 17508775
TI  - Interaction of tRNA with Safranal, Crocetin, and Dimethylcrocetin.
AB  - Saffron is the red dried stigmas of Crocus sativus L. flowers and used both as a
      spice and as a drug in traditional therapeutic. The biological activity of
      saffron in modern medicine is in development. Its numerous applications as an
      anti-oxidant and anti-cancer agent are due to its secondary metabolites and their
      derivatives (safranal, crocins, crocetin, dimethylcrocetin). The aim of this
      study was to examine the interaction of transfer RNA with safranal, crocetin, and
      dimethylcrocetin in aqueous solution at physiological conditions. Constant tRNA
      concentration (6.25 mM) and various drug/tRNA (phosphate) molar ratios of 1/48 to
      1/8 were used. FT-IR and UV-Visible difference spectroscopic methods have been
      applied to determine the drug binding mode, the binding constants and the effects
      of drug complexation on the stability and conformation of tRNA duplex. External
      binding mode was observed for safranal crocetin and dimethylcrocetin, with
      overall binding constants K(safranal) = 6.8 (+/- 0.34) x 10(3) M(-1), K(CRT) =
      1.4 (+/- 0.31) x 10(4) M(-1), and K(DMCRT) = 3.4 (+/- 0.30) x 10(4) M(-1).
      Transfer RNA remains in the A-family structure, upon safranal, crocetin and
      dimethylcrocetin complexation.

PMID- 17508776
TI  - Packing features of the all-AT oligonucleotide d(AAATTT).
AB  - We describe the packing features of the oligonucleotide duplex d(AAATTT)2, as
      determined by X-ray diffraction. There is little information on sequences that
      only contain A and T bases. The present structure confirms that these sequences
      tend to pack as a helical arrangement of stacked oligonucleotides in a B
      conformation with Watson-Crick hydrogen bonding. Our results demonstrate that the
      virtual TA base step between stacked duplexes has a negative twist that improves
      base stacking. This observation is consistent with the low stability of TA base
      steps in B-form DNA.

PMID- 17508777
TI  - Covalent binding and conformational change of pUC19 DNA by rhodium (II) metal
      complex.
AB  - Binding of Rhodium (II) acetate [Rh(2)(O(2)CCH(3))(4)] (Rh1) compound with
      plasmid pUC19 DNA has been studied using different molar ratio of Rh1. After
      incubation for 24hr at 37 degrees C, binding of the Rh1 to pUC19 DNA was
      confirmed by agarose gel electrophoresis. The electrophoretic results indicated
      the slower migration speed for the linearized pUC19 DNA. Conformation change of
      the DNA after Rh1 binding was also indicated at higher molar ratio of Rh1. The
      atomic force microscopy images showed that the Rh1 induced the conformation
      change to unwind pUC19 DNA. The Rh1-DNA complexes are observed very stable due to
      covalent bond. This study clearly demonstrates that [Rh(2)(O(2)CCH(3))(4)] reacts
      with pUC19 DNA and covalently binds to be stable Rh1-pUC19 DNA as interstrand
      adducts.

PMID- 17508778
TI  - Alkaline titrations of poly(dG-dC).poly(dG-dC): microemulsion versus solution
      behavior.
AB  - PolyGC was titrated with a strong base in the presence of increasing
      concentrations of NaCl (from 0.00 to 0.60M) either in water solution or with the
      polynucleotide solubilized in the aqueous core of reverse micelles, i.e., the
      cationic quaternary water-in-oil microemulsion CTAB/n-hexane/n-pentanol/water.
      The results for matched samples in the two media were compared. CD and UV
      spectroscopies and, for the solution experiments, pH measurements were used to
      follow the course of deprotonation. In both media the primary effect of the
      addition of base was denaturation of the polynucleotide, reversible by back
      titration with a strong acid. In solution, the apparent pK(a) of the transition
      decreases with increasing the salt concentration and a roughly linear dependence
      of pK(a) on p[NaCl] has been found. A parallel monotonic decay with ionic
      strength has been found in solution for R(OH), defined as the number of hydroxyl
      ions required per monomeric unit of polyGC to reach half-transition. By contrast,
      in microemulsion, R(OH) has been found to be independent of the NaCl
      concentration (and 10 to 50 times lower than in solution). This result is
      proposed as an indirect evidence of the independence of pK(a) on the salt
      concentration in microemulsion, where the pH cannot be measured. A sort of
      buffering effect of the positive charges on the micellar wall and of their
      counter-ions on the ionic strength could well explain this discrepancy of
      behavior in the two media.

PMID- 17508779
TI  - Effects of external transport on discrimination between perfect and mismatch
      duplexes on gel-based oligonucleotide microchips.
AB  - Using hydrogel-based oligonucleotide microchips developed previously for the
      choice of drugs during leukemia treatment and the other diseases, it is shown
      that the acceleration of external transport by mixing buffer solution with
      peristaltic pump not only enhances the observable fluorescence signals, but also
      improves significantly the discrimination between perfect and mismatch duplexes
      at the intermediate stage of hybridization on the oligonucleotide microchips. The
      discrimination efficiency for a given hybridization time grows monotonously with
      the frequency of flow pulsations. The mixing with frequency 10 Hz accelerates the
      hybridization rate approximately thrice and improves the discrimination
      efficiency 1.5-2.5 times higher for overnight hybridization. To study these
      effects, we have developed the special peristaltic pump mixing solution in a
      hybridization chamber of 35 mul in volume (area approximately 1 x 1 cm(2) and
      height 0.3 mm). We present also the brief theoretical summary for the
      interpretation and assessment of the observed experimental features.

PMID- 17508780
TI  - Mid-infrared study of deoxyadenosine at high pressures: evidence of phase
      transitions.
AB  - Room temperature mid-infrared experiments between 500 and 1800 cm(-1) have been
      performed on crystalline deoxyadenosine as a function of pressure up to about 10
      GPa. Discontinuities observed near 2 and 4 GPa indicate that two separate phase
      transitions occur at these pressures. Changes in the spectra suggest that both
      transitions involve a rearrangement of the pucker of the deoxyribose moiety. The
      wavenumbers of the vibrational modes shift to higher values with applied
      pressure. Our results for deoxyadenosine are compared to similar measurements on
      adenosine. Assignments for the observed modes are made on the basis of work
      published in the literature.

PMID- 17508781
TI  - Towards a mechanism of function of the viral ion channel Vpu from HIV-1.
AB  - Vpu, an integral membrane protein encoded in HIV-1, is implicated in the release
      of new virus particles from infected cells, presumably mediated by ion channel
      activity of homo-oligomeric Vpu bundles. Reconstitution of both full length Vpu(1
      81) and a short, the transmembrane (TM) domain comprising peptide Vpu(1-32) into
      bilayers under a constant electric field results in an asymmetric orientation of
      those channels. For both cases, channel activity with similar kinetics is
      observed. Channels can open and remain open within a broad series of conductance
      states even if a small or no electric potential is applied. The mean open time
      for Vpu peptide channels is voltage-independent. The rate of channel opening
      shows a biphasic voltage activation, implicating that the gating is influenced by
      the interaction of the dipole moments of the TM helices with an electric field.

PMID- 17508782
TI  - Structural analysis of the HIV-1 gp120 V3 loop: application to the HIV-Haiti
      isolates.
AB  - The model describing the structure and conformational preferences of the HIV
      Haiti V3 loop in the geometric spaces of Cartesian coordinates and dihedral
      angles was generated in terms of NMR spectroscopy data published in literature.
      To this end, the following successive steps were put into effect: (i) the NMR
      based 3D structure for the HIV-Haiti V3 loop in water was built by computer
      modeling methods; (ii) the conformations of its irregular segments were analyzed
      and the secondary structure elements identified; and (iii) to reveal a common
      structural motifs in the HIV-Haiti V3 loop regardless of its environment
      variability, the simulated structure was collated with the one deciphered
      previously for the HIV-Haiti V3 loop in a water/trifluoroethanol (TFE) mixed
      solvent. As a result, the HIV-Haiti V3 loop was found to offer the highly
      variable fragment of gp120 sensitive to its environment whose changes trigger the
      large-scale structural rearrangements, bringing in substantial altering the
      secondary and tertiary structures of this functionally important site of the
      virus envelope. In spite of this fact, over half of amino acid residues that
      reside, for the most part, in the functionally important regions of the gp120
      protein and may present promising targets for AIDS drug researches, were shown to
      preserve their conformational states in the structures under review. In
      particular, the register of these amino acids holds Asn-25 that is critical for
      the virus binding with primary cell receptor CD4 as well as Arg-3 that is
      critical for utilization of CCR5 co-receptor and heparan sulfate proteoglycans.
      The conservative structural motif embracing one of the potential sites of the
      gp120 N-linked glycosylation was detected, which seems to be a promising target
      for the HIV-1 drug design. The implications are discussed in conjunction with the
      literature data on the biological activity of the individual amino acids for the
      HIV-1 gp120 V3 loop.

PMID- 17508783
TI  - Excited state calculations on fluorene-based polymer blends: effect of stacking
      orientation and solvation.
AB  - Polyfluorene-based polymer blends have been utilized in the development of
      optoelectronic devices. The constituent copolymers are chemically designed to
      facilitate more efficient electron/hole mobility, thereby enhancing control over
      exciton formation and dissociation. When appropriate pairs of these are blended
      together, intermolecular charged-particle localizations are induced, leading to
      significant intermolecular charge-transfer character and luminescence that
      exhibit some sensitivity to their interfacial orientation. The authors report on
      a time-dependent density functional theory quantum chemical investigation of the
      relevant excited states of the polymer blend poly[9,9-dioctylfluorene-co-N-(4
      butylphenyl)diphenylamine]/poly(9,9-dioctylfluorene-co-benzothiadiazole. They
      show that the calculated excited states generally agree with experimental
      observations although there is a consistent underestimation of the charge
      transfer states. Further, they show sensitivity to lateral shifts in interfacial
      stacking. Finally, solvation with a low dielectric solvent greatly stabilizes the
      charge-transfer states.

PMID- 17508784
TI  - Ab initio simulation of a gadolinium-based magnetic resonance imaging contrast
      agent in aqueous solution.
AB  - The first ab initio molecular dynamics simulation of a Gd(III)-based contrast
      agent in explicit aqueous solution at ambient conditions as used in the actual
      magnetic resonance imaging of human bodies is presented. The description of the
      structure of this chelate complex is considerably improved with respect to
      typical force fields and ab initio calculations in continuum solvent models if
      the open 4f shell of Gd is included explicitly. The solvation-shell structure is
      revealed to be anionic and includes a rather short hydrogen bond donated by the
      hydroxypropyl arm.

PMID- 17508785
TI  - Morphological change during crystallization of thin amorphous solid water films
      on Ru(0001).
AB  - The isothermal crystallization process of thin amorphous solid water (ASW) films
      on Ru(0001) has been investigated in real time by simultaneously employing helium
      atom scattering, infrared reflection absorption spectroscopy, and isothermal
      temperature-programmed desorption. The measurements reveal that the
      crystallization mechanism consists of random nucleation events in the bulk of the
      ASW films, followed by homogeneous growth. Morphological changes of the solid
      water film during crystallization expose the water monolayer just above the
      substrate to the vacuum during the crystallization process.

PMID- 17508786
TI  - Two-electron reduced density matrices from the anti-Hermitian contracted
      Schrodinger equation: enhanced energies and properties with larger basis sets.
AB  - Two-electron reduced density matrices (2-RDMs) have recently been directly
      determined from the solution of the anti-Hermitian contracted Schrodinger
      equation (ACSE) to obtain 95%-100% of the ground-state correlation energy of
      atoms and molecules, which significantly improves upon the accuracy of the
      contracted Schrodinger equation (CSE) [D. A. Mazziotti, Phys. Rev. Lett. 97,
      143002 (2006)]. Two subsets of the CSE, the ACSE and the contraction of the CSE
      onto the one-particle space, known as the 1,3-CSE, have two important properties:
      (i) dependence upon only the 3-RDM and (ii) inclusion of all second-order terms
      when the 3-RDM is reconstructed as only a first-order functional of the 2-RDM.
      The error in the 1,3-CSE has an important role as a stopping criterion in solving
      the ACSE for the 2-RDM. Using a computationally more efficient implementation of
      the ACSE, the author treats a variety of molecules, including H2O, NH3, HCN, and
      HO3-, in larger basis sets such as correlation-consistent polarized double- and
      triple-zeta. The ground-state energy of neon is also calculated in a polarized
      quadruple-zeta basis set with extrapolation to the complete basis-set limit, and
      the equilibrium bond length and harmonic frequency of N2 are computed with
      comparison to experimental values. The author observes that increasing the basis
      set enhances the ability of the ACSE to capture correlation effects in ground
      state energies and properties. In the triple-zeta basis set, for example, the
      ACSE yields energies and properties that are closer in accuracy to coupled
      cluster with single, double, and triple excitations than to coupled cluster with
      single and double excitations. In all basis sets, the computed 2-RDMs very
      closely satisfy known N-representability conditions.

PMID- 17508787
TI  - Effective method to compute vibrationally resolved optical spectra of large
      molecules at finite temperature in the gas phase and in solution.
AB  - The authors present a new method for the computation of vibrationally resolved
      optical spectra of large molecules, including the Duschinsky rotation of the
      normal modes and the effect of thermal excitation. The method automatically
      selects the relevant vibronic contributions to the spectrum, independently of
      their frequency, and it is able to provide fully converged spectra with moderate
      computational times, both in vacuo and in solution. By describing the electronic
      states in the frame of the density functional theory and its time-dependent
      extension, they computed the room temperature absorption spectra of coumarin C153
      and trans-stilbene in cyclohexane and the phosphorescence spectrum of
      porphyrazine in gas phase, showing that the method is fast and efficient. The
      comparison with experiment for trans-stilbene and coumarin C153 is very
      satisfactory, confirming the progress made toward a reliable method for the
      computation and interpretation for the optical spectra of large molecules.

PMID- 17508788
TI  - "All possible steps" approach to the accelerated use of Gillespie's algorithm.
AB  - Many physical and biological processes are stochastic in nature. Computational
      models and simulations of such processes are a mathematical and computational
      challenge. The basic stochastic simulation algorithm was published by Gillespie
      about three decades ago [J. Phys. Chem. 81, 2340 (1977)]. Since then, intensive
      work has been done to make the algorithm more efficient in terms of running time.
      All accelerated versions of the algorithm are aimed at minimizing the running
      time required to produce a stochastic trajectory in state space. In these
      simulations, a necessary condition for reliable statistics is averaging over a
      large number of simulations. In this study the author presents a new accelerating
      approach which does not alter the stochastic algorithm, but reduces the number of
      required runs. By analysis of collected data the author demonstrates high
      precision levels with fewer simulations. Moreover, the suggested approach
      provides a good estimation of statistical error, which may serve as a tool for
      determining the number of required runs.

PMID- 17508789
TI  - Density functionals and transition-metal atoms.
AB  - Density-functional calculations on transition-metal atoms are problematic due to
      the numerous possible ways, having inequivalent densities, of occupying the d
      orbitals. The problem is compounded by the issue of real orbitals versus complex
      orbitals. In this work we systematize the application of density-functional
      theories to transition-metal atoms using a current-density-dependent functional.
      For all the single-determinantal angular momentum eigenstates of ground-state
      terms, we obtain near degeneracy for the energies as we should. Also, we find a
      simple rule for occupying the real d orbitals that reproduces the energies of the
      (complex) angular momentum eigenstate results. Thus the long-standing confusion
      over how to compute transition-metal atom reference energies is resolved.

PMID- 17508790
TI  - Quantum effect of intramolecular high-frequency vibrational modes on diffusion
      controlled electron transfer rate: from the weak to the strong electronic
      coupling regions.
AB  - The Sumi-Marcus theory is extended by introducing two approaches to investigate
      electron transfer reactions from weak-to-strong electronic coupling regime. One
      of these approaches is the quantum R-matrix theory, useful for dealing with the
      intramolecular vibrational motions in the whole electronic coupling domain. The
      other is the split operator approach that is employed to solve the reaction
      diffusion equation. The approaches are then applied to electron transfer in the
      Marcus inverted regime to investigate the nuclear tunneling effect on the long
      time rate and the survival probabilities. The numerical results illustrate that
      the adiabatic suppression obtained from the R-matrix approach is much smaller
      than that from the Landau-Zener theory whereas it cannot be predicted by the
      perturbation theory. The jointed effects of the electronic coupling and solvent
      relaxation time on the rates are also explored.

PMID- 17508791
TI  - Time-dependent density functional theory scheme for efficient calculations of
      dynamic (hyper)polarizabilities.
AB  - The authors present an efficient perturbative method to obtain both static and
      dynamic polarizabilities and hyperpolarizabilities of complex electronic systems.
      This approach is based on the solution of a frequency-dependent Sternheimer
      equation, within the formalism of time-dependent density functional theory, and
      allows the calculation of the response both in resonance and out of resonance.
      Furthermore, the excellent scaling with the number of atoms opens the way to the
      investigation of response properties of very large molecular systems. To
      demonstrate the capabilities of this method, they implemented it in a real-space
      (basis-set-free) code and applied it to benchmark molecules, namely, CO, H2O, and
      para-nitroaniline. Their results are in agreement with experimental and previous
      theoretical studies and fully validate their approach.

PMID- 17508792
TI  - New mixed quantumsemiclassical propagation method.
AB  - The authors developed a new method for calculating the quantum evolution of
      multidimensional systems, for cases in which the system can be assumed to consist
      of a quantum subsystem and a bath subsystem of heavier atoms. The method combines
      two ideas: starting from a simple frozen Gaussian description of the bath
      subsystem, then calculate quantum corrections to the propagation of the quantum
      subsystem. This follows from recent work by one of them, showing how one can
      calculate corrections to approximate evolution schemes, even when the Hamiltonian
      that corresponds to these approximate schemes is unknown. Then, they take the
      limit in which the width of the frozen Gaussians approaches zero, which makes the
      corrections to the evolution of the quantum subsystem depend only on classical
      bath coordinates. The test calculations they present use low-dimensional systems,
      in which comparison to exact quantum dynamics is feasible.

PMID- 17508793
TI  - Interpolating moving least-squares methods for fitting potential energy surfaces:
      computing high-density potential energy surface data from low-density ab initio
      data points.
AB  - A highly accurate and efficient method for molecular global potential energy
      surface (PES) construction and fitting is demonstrated. An interpolating-moving
      least-squares (IMLS)-based method is developed using low-density ab initio
      Hessian values to compute high-density PES parameters suitable for accurate and
      efficient PES representation. The method is automated and flexible so that a PES
      can be optimally generated for classical trajectories, spectroscopy, or other
      applications. Two important bottlenecks for fitting PESs are addressed. First,
      high accuracy is obtained using a minimal density of ab initio points, thus
      overcoming the bottleneck of ab initio point generation faced in applications of
      modified-Shepard-based methods. Second, high efficiency is also possible
      (suitable when a huge number of potential energy and gradient evaluations are
      required during a trajectory calculation). This overcomes the bottleneck in high
      order IMLS-based methods, i.e., the high cost/accuracy ratio for potential energy
      evaluations. The result is a set of hybrid IMLS methods in which high-order IMLS
      is used with low-density ab initio Hessian data to compute a dense grid of points
      at which the energy, Hessian, or even high-order IMLS fitting parameters are
      stored. A series of hybrid methods is then possible as these data can be used for
      neural network fitting, modified-Shepard interpolation, or approximate IMLS.
      Results that are indicative of the accuracy, efficiency, and scalability are
      presented for one-dimensional model potentials as well as for three-dimensional
      (HCN) and six-dimensional (HOOH) molecular PESs.

PMID- 17508794
TI  - Phase-space approach to dynamical density functional theory.
AB  - The authors consider a system of interacting particles subjected to Langevin
      inertial dynamics and derive the governing time-dependent equation for the one
      body density. They show that, after suitable truncations of the Bogoliubov-Born
      Green-Kirkwood-Yvon hierarchy, and a multiple time scale analysis, they obtain a
      self-consistent equation involving only the one-body density. This study extends
      to arbitrary dimensions previous work on a one-dimensional fluid and highlights
      the subtleties of kinetic theory in the derivation of dynamical density
      functional theory.

PMID- 17508795
TI  - Enveloping distribution sampling: a method to calculate free energy differences
      from a single simulation.
AB  - The authors present a method to calculate free energy differences between two
      states A and B "on the fly" from a single molecular dynamics simulation of a
      reference state R. No computer time has to be spent on the simulation of
      intermediate states. Only one state is sampled, i.e., the reference state R which
      is designed such that the subset of phase space important to it is the union of
      the parts of phase space important to A and B. Therefore, an accurate estimate of
      the relative free energy can be obtained by construction. The authors applied the
      method to four test systems (dipole inversion, van der Waals interaction
      perturbation, charge inversion, and water to methanol conversion) and compared
      the results to thermodynamic integration estimates. In two cases, the enveloping
      distribution sampling calculation was straightforward. However, in the charge
      inversion and the water to methanol conversion, Hamiltonian replica-exchange
      molecular dynamics of the reference state was necessary to observe transitions in
      the reference state simulation between the parts of phase space important to A
      and B, respectively. This can be explained by the total absence of phase space
      overlap of A and B in these two cases.

PMID- 17508796
TI  - Molecular dynamics simulation with stochastically constrained pressure.
AB  - The authors propose a new algorithm for molecular dynamics simulation. The method
      includes a Monte Carlo scheme for incrementing the dilation rate in the equations
      of motion. The new algorithm needs no extra computation and the dynamics of the
      system preserves its continuity. Application of this approach is very
      advantageous for models where the derivation and the computation of the pressure
      is time consuming. The authors present results of model calculations.

PMID- 17508797
TI  - Experimental and theoretical studies of the electronic structure and the
      ionization and dissociation processes of trifluoromethyl peroxynitrate.
AB  - In this work, we present a complete study of the ionization and dissociation
      processes for trifluoromethyl peroxynitrate (CF3OONO2). CF3OONO2 was generated by
      UV photolysis of a mixture of (CF3CO)2O, NO2, and O2. The product was detected
      and characterized by the photoelectron spectroscopy (PES) and photoionization
      mass spectroscopy (PIMS). The geometric and electronic structures of CF3OONO2
      were investigated by the combination of experiments and the density functional
      and ab initio calculations. It is worthwhile mentioning that drastic changes
      occur in the geometry of CF3OONO2 after ionization. Due to the removal of one
      electron from the O-N sigma bond, the COON dihedral angle changes to 180 degrees
      and as a result, the nonplanar structure becomes planar. And the O-N single bond
      length increases remarkably, with the positive charge most localized on the NO2
      moiety. The experimental first vertical ionization potential is 12.39 eV. Based
      on the calculated bond dissociation energies, the dissociation pathway was
      predicted. The calculated results explain the ion intensities observed in the
      photoionization mass spectrum. The dissociation of O-N single bond is found to be
      the most favored of the possible dissociation paths for CF3OONO2+.

PMID- 17508798
TI  - CAl4X (X=Si,Ge): molecules with simultaneous planar tetracoordinate carbon,
      aluminum, and silicon/germanium.
AB  - The authors report the first theoretical study on the hexa-atomic molecules
      CAl(4)X (X=Si,Ge) at the B3LYP/6-311++G(2d), MP2/6-311++G(2d), and CCSD(T)/6
      311++G(3df) (single point) levels. Three low-lying isomers (within 2.0 kcal/mol)
      can be formally viewed as constructed by one Al+ interacting with the planar
      CAl3X- at the side Al-X bond (X-1), side Al-Al bond (X-2), and central C atom (X
      3). The isomers X-1 and X-2 both have planar structures that include the planar
      tetracoordinate carbon, aluminum, and silicon/germanium, while the three
      dimensional isomer X-3 has the pentacoordinate carbon. The planarity of X-1 and X
      2 is ascribed to the ligand five-center two-electron bonding molecular orbital,
      similar to the orbital responsible for the planarity of CAl3X- (X=Si,Ge).
      Kinetically, the two planar structures X-1 and X-2 can be easily interconverted
      to each other via the intermediate X-3, indicative of their coexistence. Of
      particular interest, isomer X-1 represents the first example that simultaneously
      contains three types of planar centers in a single molecule, to the best of our
      knowledge. The three low-lying and structurally interesting isomers X-1, X-2, and
      X-3 await future experimental verification. The present results could enrich the
      planar chemistry.

PMID- 17508799
TI  - Spin-orbit relaxation of Cl(2P1/2) and F(2P1/2) in a gas of H2.
AB  - The authors present quantum scattering calculations of rate coefficients for the
      spin-orbit relaxation of F(2P1/2) atoms in a gas of H2 molecules and Cl(2P1/2)
      atoms in a gas of H2 and D2 molecules. Their calculation of the thermally
      averaged rate coefficient for the electronic relaxation of chlorine in H2 agrees
      very well with an experimental measurement at room temperature. It is found that
      the spin-orbit relaxation of chlorine atoms in collisions with hydrogen molecules
      in the rotationally excited state j=2 is dominated by the near-resonant
      electronic-to-rotational energy transfer accompanied by rotational excitation of
      the molecules. The rate of the spin-orbit relaxation in collisions with D2
      molecules increases to a great extent with the rotational excitation of the
      molecules. They have found that the H2/D2 isotope effect in the relaxation of
      Cl(2P1/2) is very sensitive to temperature due to the significant role of
      molecular rotations in the nonadiabatic transitions. Their calculation yields a
      rate ratio of 10 for the electronic relaxation in H2 and D2 at room temperature,
      in qualitative agreement with the experimental measurement of the isotope ratio
      of about 5. The isotope effect becomes less significant at higher temperatures.

PMID- 17508800
TI  - Combined vacuum ultraviolet laser and synchrotron pulsed field ionization study
      of CH2BrCl.
AB  - The pulsed field ionization-photoelectron (PFI-PE) spectrum of bromochloromethane
      (CH2BrCl) in the region of 85,320-88,200 cm-1 has been measured using vacuum
      ultraviolet laser. The vibrational structure resolved in the PFI-PE spectrum was
      assigned based on ab initio quantum chemical calculations and Franck-Condon
      factor predictions. At energies 0-1400 cm-1 above the adiabatic ionization energy
      (IE) of CH2BrCl, the Br-C-Cl bending vibration progression (nu1+=0-8) of CH2BrCl+
      is well resolved and constitutes the major structure in the PFI-PE spectrum,
      whereas the spectrum at energies 1400-2600 cm-1 above the IE(CH2BrCl) is found to
      exhibit complex vibrational features, suggesting perturbation by the low lying
      excited CH2BrCl+(A 2A") state. The assignment of the PFI-PE vibrational bands
      gives the IE(CH2BrCl)=85,612.4+/-2.0 cm-1 (10.6146+/-0.0003 eV) and the bending
      frequencies nu1+(a1')=209.7+/-2.0 cm-1 for CH2BrCl+(X2A'). We have also examined
      the dissociative photoionization process, CH2BrCl+hnu-->CH2Cl++Br+e-, in the
      energy range of 11.36-11.57 eV using the synchrotron based PFI-PE-photoion
      coincidence method, yielding the 0 K threshold or appearance energy
      AE(CH2Cl+)=11.509+/-0.002 eV. Combining the 0 K AE(CH2Cl+) and IE(CH2BrCl) values
      obtained in this study, together with the known IE(CH2Cl), we have determined the
      0 K bond dissociation energies (D0) for CH2Cl+-Br (0.894+/-0.002 eV) and CH2Cl-Br
      (2.76+/-0.01 eV). We have also performed CCSD(T, full)/complete basis set (CBS)
      calculations with high-level corrections for the predictions of the IE(CH2BrCl),
      AE(CH2Cl+), IE(CH2Cl), D0(CH2Cl+-Br), and D0(CH2Cl-Br). The comparison between
      the theoretical predictions and experimental determinations indicates that the
      CCSD(T, full)/CBS calculations with high-level corrections are highly reliable
      with estimated error limits of <17 meV.

PMID- 17508801
TI  - Nuclear quadrupole moment of 197Au from high-accuracy atomic calculations.
AB  - The electric field gradient (EFG) at the gold nucleus is calculated using a
      finite field approach, to make the extraction of the nuclear quadrupole moment Q
      from experimental nuclear quadrupole coupling constants possible. The four
      component Dirac-Coulomb Hamiltonian serves as the framework, 51 of the 79
      electrons are correlated by the relativistic Fock-space coupled cluster method
      with single and double excitations, and the contribution of the Gaunt term, the
      main part of the Breit interaction, is evaluated. Large basis sets (up to
      26s22p18d12f8g5h uncontracted Gaussians) are employed. Energy splittings of the
      2D5/2 and 2D3/2 levels, rather than level shifts, are used to extract the EFG
      constants, as the former remain linear with Q up to 10(-5) a.u., whereas the
      latter display significant nonlinearity even at Q=10(-8) a.u. Larger Q values
      lead to larger energy changes and better precision. Excellent agreement (0.1%) is
      obtained between Q values derived from 2D5/2 and 2D3/2 data. Systematic errors
      connected with neglecting triple and higher excitations, truncating the basis and
      orbital active space, and approximating the Gaunt contribution are evaluated. The
      final value of Q(197Au) is 521(7) mb. It is lower than the muonic 547(16) mb and
      agrees within error bounds with the recent value of 510(15) mb obtained from
      molecular calculations.

PMID- 17508802
TI  - Photoelectron studies of neutral Ag3 in helium droplets.
AB  - Photoelectron spectra of neutral silver trimers, grown in ultracold helium
      nanodroplets, are recorded after ionization with laser pulses via a strong
      optical resonance of this species. Varying the photon energy reveals that direct
      vertical two-photon ionization is hindered by a rapid relaxation into the lower
      edge of a long-living excited state manifold. An analysis of the ionization
      threshold of the embedded trimer yields an ionization potential of 5.74+/-0.09 eV
      consistent with the value found in the gas phase. The asymmetrical form of the
      electron energy spectrum, which is broadened toward lower kinetic energies, is
      attributed to the influence of the matrix on the photoionization process. The
      lifetime of the excited state was measured in a two-color pump-probe experiment
      to be 5.7+/-0.6 ns.

PMID- 17508803
TI  - Studies of intersystem crossing dynamics in acetylene.
AB  - We report a new ab initio study of the acetylene T3 potential energy surface,
      which clarifies the nature of its energy minimum, and present computed
      equilibrium geometries and diabatic frequencies. This information enables the
      computation of harmonic vibrational overlap integrals of T3 vibrational levels
      with the S1 3nu3 state. The results of this calculation support the
      interpretation of two local perturbations of S1 3nu3, revealed in ultraviolet
      laser-induced fluorescence/surface electron ejection by laser excited metastables
      spectroscopy and Zeeman anticrossing measurements, respectively, as arising from
      two rotational submanifolds of a single T3 vibrational state. We present
      plausible assignments for this state as a guide for future experimental work.

PMID- 17508804
TI  - Cross sections and rate constants for the C(3P)+OH(X 2Pi)-->CO(X 1Sigma+)+H(2S)
      reaction using a quasiclassical trajectory method.
AB  - First quasiclassical trajectory calculations have been carried out for the
      C(3P)+OH(X 2Pi)-->CO(X 1Sigma+)+H(2S) reaction using a recent ab initio potential
      energy surface for the ground electronic state, X 2A', of HCO/COH. Total and
      state-specific integral cross sections have been determined for a wide range of
      collision energies (0.001-1 eV). Then, thermal and state-specific rate constants
      have been calculated in the 1-500 K temperature range. The thermal rate constant
      varies from 1.78x10(-10) cm3 s-1 at 1 K down to 5.96x10(-11) cm3 s-1 at 500 K
      with a maximum value of 3.39x10(-10) cm3 s-1 obtained at 7 K. Cross sections and
      rate constants are found to be almost independent of the rovibrational state of
      OH.

PMID- 17508805
TI  - Vibronic and spin-orbit coupling of a d9 transition-metal ion encapsulated in an
      icosahedral cage: the (Gamma8+Gamma9)x(g+2h) Jahn-Teller problem.
AB  - Interplay between the vibronic and spin-orbit coupling in the
      (Gamma8+Gamma9)x(g+2h) Jahn-Teller problem, where Gamma8 and Gamma9 are the
      quartet and sextet spin representation, and g and h denote the fourfold and
      fivefold degenerate vibrational modes in icosahedral symmetry, respectively, is
      studied. A 4d9 or 5d9 transition-metal ion in an icosahedral field may provide a
      realization of this system.

PMID- 17508806
TI  - A systematic enumeration of local topological relaxation mechanisms in amorphous
      networks and their efficiency in network relaxation.
AB  - We consider the infinite hierarchy of local collective rearrangements on bond
      networks that preserves the valency of each atom and explicitly enumerate those
      involving 4, 5, and 6 particles. The only 4-particle rearrangement is identical
      to the Wooten-Winer-Weaire (WWW) mechanism. Each rearrangement mechanism is
      applied in a Monte Carlo (MC) algorithm in order to determine the rate at which
      it equilibrate a network and relax the structure at equilibrium. At low
      temperature the 4-particle mechanism provides the fastest relaxation rate but we
      find that there is a crossover with increasing temperature to 5-particle
      mechanisms.

PMID- 17508807
TI  - Spontaneous and induced dynamic fluctuations in glass formers. I. General results
      and dependence on ensemble and dynamics.
AB  - We study theoretically and numerically a family of multipoint dynamic
      susceptibilities that quantify the strength and characteristic length scales of
      dynamic heterogeneities in glass-forming materials. We use general theoretical
      arguments (fluctuation-dissipation relations and symmetries of relevant dynamical
      field theories) to relate the sensitivity of averaged two-time correlators to
      temperature and density to spontaneous fluctuations of the local dynamics. Our
      theoretical results are then compared to molecular dynamics simulations of the
      Newtonian, Brownian, and Monte Carlo dynamics of two representative glass-forming
      liquids, a fragile binary Lennard-Jones mixture, and a model for the strong glass
      former silica. We justify in detail the claim made by Berthier et al. [Science
      310, 1797 (2005)] that the temperature dependence of correlation functions allows
      one to extract useful information on dynamic length scales in glassy systems. We
      also discuss some subtle issues associated with the choice of microscopic
      dynamics and of statistical ensemble through conserved quantities, which are
      found to play an important role in determining dynamic correlations.

PMID- 17508808
TI  - Spontaneous and induced dynamic correlations in glass formers. II. Model
      calculations and comparison to numerical simulations.
AB  - We study in detail the predictions of various theoretical approaches, in
      particular, mode-coupling theory (MCT) and kinetically constrained models (KCMs),
      concerning the time, temperature, and wave vector dependence of multipoint
      correlation functions that quantify the strength of both induced and spontaneous
      dynamical fluctuations. We also discuss the precise predictions of MCT concerning
      the statistical ensemble and microscopic dynamics dependence of these multipoint
      correlation functions. These predictions are compared to simulations of model
      fragile and strong glass-forming liquids. Overall, MCT fares quite well in the
      fragile case, in particular, explaining the observed crucial role of the
      statistical ensemble and microscopic dynamics, while MCT predictions do not seem
      to hold in the strong case. KCMs provide a simplified framework for understanding
      how these multipoint correlation functions may encode dynamic correlations in
      glassy materials. However, our analysis highlights important unresolved questions
      concerning the application of KCMs to supercooled liquids.

PMID- 17508809
TI  - High P-T transformations of nitrogen to 170 GPa.
AB  - X-ray diffraction and optical spectroscopy techniques are used to characterize
      stable and metastable transformations of nitrogen compressed up to 170 GPa and
      heated above 2500 K. X-ray diffraction data show that varepsilon-N2 undergoes two
      successive structural changes to complex molecular phases zeta at 62 GPa and a
      newly discovered kappa at 110 GPa. The latter becomes an amorphous narrow gap
      semiconductor on further compression and if subjected to very high temperatures
      (approximately 2000 K) crystallizes to the crystalline cubic-gauche-N structure
      (cg-N) above 150 GPa. The diffraction data show that the transition to cg-N is
      accompanied by 15% volume reduction.

PMID- 17508810
TI  - Infrared spectra of N2O-(ortho-D2)N and N2O-(HD)N clusters trapped in bulk solid
      parahydrogen.
AB  - High-resolution infrared spectra of the clusters N2O-(ortho-D2)N and N2O-(HD)N,
      N=1-4, isolated in bulk solid parahydrogen at liquid helium temperatures are
      studied in the 2225 cm-1 region of the nu3 antisymmetric stretch of N2O. The
      clusters form during vapor deposition of separate gas streams of a precooled
      hydrogen mixture (ortho-D2para-H2 or HDpara-H2) and N2O onto a BaF2 optical
      substrate held at approximately 2.5 K in a sample-in-vacuum liquid helium
      cryostat. The cluster spectra reveal the N2O nu3 vibrational frequency shifts to
      higher energy as a function of N, and the shifts are larger for ortho-D2 compared
      to HD. These vibrational shifts result from the reduced translational zero-point
      energy for N2O solvated by the heavier hydrogen isotopomers. These spectra allow
      the N=0 peak at 2221.634 cm-1, corresponding to the nu3 vibrational frequency of
      N2O isolated in pure solid parahydrogen, to be assigned. The intensity of the N=0
      absorption feature displays a strong temperature dependence, suggesting that
      significant structural changes occur in the parahydrogen solvation environment of
      N2O in the 1.8-4.9 K temperature range studied.

PMID- 17508811
TI  - Infrared spectroscopy of aqueous ionic salt solutions at low concentrations.
AB  - The analysis by infrared spectroscopy of aqueous solutions of the binary
      inorganic salts NaI and NaCl and the ternary salts CaCl2 and BaCl2 at
      concentrations from 1000 to 2 mM was carried out to complement a previous study
      done at higher concentrations on nine binary salts (alkali halides) and one
      ternary salt (MgCl2) [J.-J. Max and C. Chapados, J. Chem. Phys. 115, 2664
      (2001)]. These salts are completely ionized in aqueous solutions, forming
      monoatomic species that do not absorb IR but that perturb the surrounding water,
      modifying its spectrum. The factor analysis of the spectra revealed that all
      these salt solutions were composed of two water types: pure water and salt
      solvated water. The authors obtained pure salt solvated water spectra for all the
      salts using an extrapolation technique. The water types obtained are constant for
      the binary and ternary salts down to 2 mM. For the binary salts, we determine
      that 5.0 and 4.0 water molecules are solvated to the Na+-Cl- and Na+-I- ion
      pairs, respectively. These numbers are the same as that obtained at higher
      concentrations. For the new ternary salts, we find that 6.0 and 8.0 water
      molecules are solvated to Ca++-(Cl-)2 and Ba++-(Cl-)2 ion pairs, respectively.
      These numbers are higher than the four water molecules solvated to Mg++-(Cl-)2
      ion pairs determined previously, but show a progression that follows their atomic
      numbers. These results constitute new experimental results on "simple" systems
      whose molecular organization is still a matter of debate. The IR method that
      probes the system at the molecular level is a method different than the
      macroscopic ones that give the activity coefficients. The IR gives direct
      observation at the molecular level of the strong ion-water interactions that are
      often neglected and its water structure not considered in macroscopic methods.
      The present results and their analysis together with those obtained by other
      methods will facilitate the determination of the organization of these aqueous
      systems.

PMID- 17508812
TI  - Classical interaction model for the water molecule.
AB  - The authors propose a new classical model for the water molecule. The geometry of
      the molecule is built on the rigid TIP5P model and has the experimental gas phase
      dipole moment of water created by four equal point charges. The model preserves
      its rigidity but the size of the charges increases or decreases following the
      electric field created by the rest of the molecules. The polarization is
      expressed by an electric field dependent nonlinear polarization function. The
      increasing dipole of the molecule slightly increases the size of the water
      molecule expressed by the oxygen-centered sigma parameter of the Lennard-Jones
      interaction. After refining the adjustable parameters, the authors performed
      Monte Carlo simulations to check the ability of the new model in the ice, liquid,
      and gas phases. They determined the density and internal energy of several ice
      polymorphs, liquid water, and gaseous water and calculated the heat capacity, the
      isothermal compressibility, the isobar heat expansion coefficients, and the
      dielectric constant of ambient water. They also determined the pair-correlation
      functions of ambient water and calculated the energy of the water dimer. The
      accuracy of theirs results was satisfactory.

PMID- 17508813
TI  - Electrical conductivity and relaxation in mixed alkali tellurite glasses.
AB  - The authors have reported the electrical conductivity and the conductivity
      relaxation in mixed alkali tellurite glasses of compositions of 70TeO2-xNa2O-(30
      x)Li2O in the frequency range from 10 Hz to 2 MHz and in the temperature range
      from room temperature to just below the glass transition temperature. They have
      analyzed the relaxation data in the framework of different models. They have
      observed the mixed alkali effect in the dc and ac conductivities, the crossover
      frequency, and the conductivity relaxation frequency as well as in their
      respective activation energies in these glasses. They have also observed the
      mixed alkali effect in the decoupling index. The scaling property of the modulus
      spectra of these mixed alkali glasses shows that the conductivity relaxation in
      the mixed alkali tellurite glasses is independent of temperature but depends on
      the glass compositions.

PMID- 17508814
TI  - Influence of vapor depletion on nucleation rate.
AB  - During condensation in finite systems part of molecules is transformed from
      supersaturated mother phase to a new one and depletion of the mother phase
      occurs. Kinetic equations describing homogeneous nucleation process including
      decrease of supersaturation are solved numerically. It is shown that dependency
      of nucleation rate on nucleus size reaches some maximum, which decreases with
      time and moves to higher nucleus sizes. Nucleation rate is negative for
      undercritical size of nuclei.

PMID- 17508815
TI  - Continuously broken ergodicity.
AB  - A system that is initially ergodic can become nonergodic, i.e., display "broken
      ergodicity," if the relaxation time scale of the system becomes longer than the
      observation time over which properties are measured. The phenomenon of broken
      ergodicity is of vital importance to the study of many condensed matter systems.
      While previous modeling efforts have focused on systems with a sudden,
      discontinuous loss of ergodicity, they cannot be applied to study a gradual
      transition between ergodic and nonergodic behavior. This transition range, where
      the observation time scale is comparable to that of the structural relaxation
      process, is especially pertinent for the study of glass transition range
      behavior, as ergodicity breaking is an inherently continuous process for normal
      laboratory glass formation. In this paper, we present a general statistical
      mechanical framework for modeling systems with continuously broken ergodicity.
      Our approach enables the direct computation of entropy loss upon ergodicity
      breaking, accounting for actual transition rates between microstates and
      observation over a specified time interval. In contrast to previous modeling
      efforts for discontinuously broken ergodicity, we make no assumptions about phase
      space partitioning or confinement. We present a hierarchical master equation
      technique for implementing our approach and apply it to two simple one
      dimensional landscapes. Finally, we demonstrate the compliance of our approach
      with the second and third laws of thermodynamics.

PMID- 17508816
TI  - Transport and Helfand moments in the Lennard-Jones fluid. I. Shear viscosity.
AB  - The authors propose a new method, the Helfand-moment method, to compute the shear
      viscosity by equilibrium molecular dynamics in periodic systems. In this method,
      the shear viscosity is written as an Einstein-type relation in terms of the
      variance of the so-called Helfand moment. This quantity is modified in order to
      satisfy systems with periodic boundary conditions usually considered in molecular
      dynamics. They calculate the shear viscosity in the Lennard-Jones fluid near the
      triple point thanks to this new technique. They show that the results of the
      Helfand-moment method are in excellent agreement with the results of the standard
      Green-Kubo method.

PMID- 17508817
TI  - Transport and Helfand moments in the Lennard-Jones fluid. II. Thermal
      conductivity.
AB  - The thermal conductivity is calculated with the Helfand-moment method in the
      Lennard-Jones fluid near the triple point. The Helfand moment of thermal
      conductivity is here derived for molecular dynamics with periodic boundary
      conditions. Thermal conductivity is given by a generalized Einstein relation with
      this Helfand moment. The authors compute thermal conductivity by this new method
      and compare it with their own values obtained by the standard Green-Kubo method.
      The agreement is excellent.

PMID- 17508818
TI  - Surface excess free energy of simple fluids confined in cylindrical pores by
      isothermal-isobaric Monte Carlo: influence of pore size.
AB  - Confined fluid properties are mainly determined by interfacial phenomena
      characterized by surface quantities. Based on a simple model of Lennard-Jones
      particles confined in a cylindrical pore, this study introduces a grand potential
      surface quantity to quantify the difference in the thermodynamic pressure between
      the bulk and the confined fluids. The usual surface tension gamma defined as this
      grand potential difference for the same chemical potential in both confined and
      bulk states is generally strongly dependent on both the chemical potential and
      temperature. It is proposed here to introduce another surface quantity zeta which
      measures the thermodynamic pressure difference between confined and bulk states
      for identical densities. It is shown that this quantity is much less dependent on
      confined fluid density or chemical potential. It is actually constant along the
      gas-like and liquid-like adsorption/desorption branches for an irreversible
      isotherm (hysteresis), with a different value for each branch. For reversible
      supercritical isotherms, zeta is shown to remain constant in the low and high
      density parts of the isotherm. This independence on chemical potential (or
      equivalently fluid density) is believed to be of great interest for practical
      applications when one desires to calculate thermodynamic quantities such as the
      usual surface tension gamma or the thermodynamic pressure of a confined fluid for
      any given chemical potential and temperature. Such calculations are required to
      determine fundamental properties such as metastability or coexistence. The
      effects of temperature, fluid/substrate interaction strength, and pore size are
      studied.

PMID- 17508819
TI  - Ionization of H2 Rydberg molecules at a metal surface.
AB  - The ionization of a beam of H2 Rydberg molecules in collision with a metal
      surface (evaporated Au or Al) is studied. The Rydberg states are excited in an
      ultraviolet-vacuum ultraviolet double-resonant process and are state selected
      with a core rotational quantum number N+=0 or 2 and principal quantum numbers
      n=17-22 (N+=2) or n=41-45 (N+=0). It is found that the N+=0 states behave in a
      very similar manner to previous studies with atomic xenon Rydberg states, the
      distance of ionization from the surface scaling with n2. The N+=2 states,
      however, undergo a process of surface-induced rotational autoionization in which
      the core rotational energy transfers to the Rydberg electron. In this case the
      ionization distance scales approximately with nu0(2), the effective principal
      quantum number with respect to the adiabatic threshold. This process illustrates
      the close similarity between field ionization in the gas phase and the surface
      ionization process which is induced by the field due to image charges in the
      metal surface. The surface ionization rate is enhanced at certain specific values
      of the field, which is applied in the time interval between excitation and
      surface interaction. It is proposed here that these fields correspond to level
      crossings between the N+=0 and N+=2 Stark manifolds. The population of individual
      states of the N+=2, n=18 Stark manifold in the presence of a field shows that the
      surface-induced rotational autoionization is more facile for the blueshifted
      states, whose wave function is oriented away from the surface, than for the
      redshifted states. The observed processes appear to show little dependence on the
      chemical nature of the metallic surface, but a significant change occurs when the
      surface roughness becomes comparable to the Rydberg orbit dimensions.

PMID- 17508820
TI  - Ab initio investigation of ammonia-borane complexes for hydrogen storage.
AB  - The structural, electronic, and thermodynamic properties of ammonia-borane
      complexes with varying amounts of hydrogen have been characterized by first
      principles calculations within density functional theory. The calculated
      structural parameters and thermodynamic functions (free energy, enthalpy and
      entropy) were found to be in good agreement with experimental and quantum
      chemistry data for the crystals, dimers, and molecules. The authors find that
      zero-point energies change several H2 release reactions from endothermic to
      exothermic. Both the ammonia-borane polymeric and borazine-cyclotriborazane
      cycles show a strong exothermic decomposition character (approximately -10
      kcal/mol), implying that rehydrogenation may be difficult to moderate H2
      pressures. Hydrogen bonding in these systems has been characterized and they find
      the N-H bond to be more covalent than the more ionic B-H bond.

PMID- 17508821
TI  - Hydrodynamic interactions between spheres in a viscous fluid with a flat free
      surface or hard wall.
AB  - Hydrodynamic interactions between spheres immersed in a low-Reynolds-number fluid
      flow close to a flat free surface or hard wall are investigated. The spheres may
      have different or equal radii, and may be separated from the boundary or at
      contact with the free surface. A simple and useful expression is derived for the
      propagator (Green operator) connecting centers of two spheres. In the derivation,
      the method of images and the displacement theorems are used. Symmetry of the
      displacement operators is explicitly shown. The significance of these results in
      efficient Stokesian and Brownian dynamics simulations is outlined. An example of
      an application is shown.

PMID- 17508822
TI  - Roughing titanium quantum wire on patterned monohydride diamond (001) surface.
AB  - The authors have performed the roughing of titanium (Ti) quantum wires forming on
      a hydrogen-terminated diamond (001)-2x1 surface patterned with an ordered bare
      strip array and demonstrated that well-ordered Ti quantum wires are achieved only
      if the growth conditions (temperature and flux) have optimal values via kinetic
      Monte Carlo simulations. Considering that a scanning tunneling microscope is
      capable of selectively desorbing H from diamond (001)-2x1-H surface, they
      proposed a viable and easy approach to fabricate "ideal quantum wires" on the
      patterned hydrogen-terminated diamond (001) surface. The physical origin of the
      Ti quantum wire formation was pursued.

PMID- 17508823
TI  - Electronic and structural properties of oligophenylene ethynylenes on Au(111)
      surfaces.
AB  - The interaction of oligophenylene ethynylene (OPE) on the (111) surface of a gold
      slab resembling a self-assembled monolayer (SAM) is investigated using ab initio
      density functional theory calculations. The authors performed a full optimization
      including all atoms in the OPE and in the slab to better understand OPE
      adsorption on the surface. It is found that OPE has two energetically favorable
      adsorption sites on the Au surface with relatively different molecular
      geometries: the nontop site adsorption greatly modifies the (111) surface
      structure; however, the extensive electron interactions enable a delocalized
      electron density distribution, implying an improved conductivity between OPE and
      Au, and the top site which is 0.9 eV higher in energy than the nontop and
      features weaker Au-S bonds. Interestingly the on top configuration shows a strong
      spin imbalance along the molecule and the nontop shows a small spin imbalance on
      the surface. This feature is of strong interest for the development of resonators
      for the detection of chemical and biological agents. They have also calculated
      the frequency spectrum of these SAMs, which yield deformations in the gold
      surface yielding peak frequency shifts specific to each absorption site.

PMID- 17508824
TI  - Resonant processes and Coulomb interactions in (C59N)2.
AB  - We have determined the on-site molecular Coulomb interaction energy U of a
      (C59N)2 bulk film and find values ranging from 1.10+/-0.10 eV for the highest
      occupied molecular orbital to 1.35+/-0.10 eV for the deeper lying orbitals,
      comparable to values found in C60. The on-site Coulomb interaction between a
      carbon core hole and valence electrons, Uc, is, however, substantially lower than
      in C60 at 1.35+/-0.07 eV. Resonant photoemission (RESPES) results show a weakened
      participator decay channel, especially around the N 1s threshold, where resonance
      of the highest occupied molecular orbital shoulder is absent. Near-edge x-ray
      absorption fine structure and constant initial state measurements, taken in
      parallel with the RESPES data, indicate, however, that matrix element effects
      cannot be ruled out.

PMID- 17508825
TI  - Ultrafast optical Kerr effect spectroscopy of water confined in nanopores of the
      gelatin gel.
AB  - We report on the investigation of a short-time collective dynamics of water
      confined in the pores of the gelatin gel, using the femtosecond optical Kerr
      effect spectroscopy. The ultrafast responses of water molecules obtained in bulk
      liquid and in three concentrations of gelatin gels are explained theoretically,
      both in a long time and in a short time regime, taking into account all molecular
      motions. We prove that the contribution of molecules involved in tetrahedral,
      strongly H-bonded structures stabilizing the gel network increases with the gel
      concentration. On the other hand the long-time relaxation of water molecules is
      significantly slowed down in the gel pores.

PMID- 17508826
TI  - On the dissipative effects in the electron transport through conducting polymer
      nanofibers.
AB  - Here, the author studies the effects of stochastic nuclear motions on the
      electron transport in doped polymer fibers assuming the conducting state of the
      material. The author treats conducting polymers as granular metals and applies
      the quantum theory of conduction in mesoscopic systems to describe the electron
      transport between metalliclike granules. To analyze the effects of nuclear
      motions, the author mimics them by a phonon bath and includes electron-phonon
      interactions in consideration. The results show that the phonon bath plays a
      crucial part in the intergrain electron transport at moderately low and room
      temperatures, suppressing the original intermediate state for the resonance
      electron tunneling and producing new states which support the electron transport.
      Also, the temperature dependence of the magnitudes of the peaks in the electron
      transmission corresponding to these new states is analyzed.

PMID- 17508827
TI  - Fluorescence lifetime fluctuations of single molecules probe the local
      environment of oligomers around the glass transition temperature.
AB  - Single molecule fluorescence experiments have been performed on a BODIPY-based
      dye embedded in oligo(styrene) matrices to probe the density fluctuations and the
      relaxation dynamics of chain segments surrounding the dye molecules. The time
      dependent fluorescence lifetime of the BODIPY probe was recorded as an observable
      for the local density fluctuations. At room temperature, the mean fraction of
      holes surrounding the probes is shown to be unaffected by the molecular weight in
      the glassy state. In contrast, the free volume increases significantly in the
      supercooled regime. These observations are discussed in the framework of the
      entropic theories of the glass transition.

PMID- 17508828
TI  - Effect of chain length on fragility and thermodynamic scaling of the local
      segmental dynamics in poly(methylmethacrylate).
AB  - Local segmental relaxation properties of poly(methylmethacrylate) (PMMA) of
      varying molecular weight are measured by dielectric spectroscopy and analyzed in
      combination with the equation of state obtained from PVT measurements.
      Significant variations of glass transition temperature and fragility with
      molecular weight are observed. In accord with the general properties of glass
      forming materials, single molecular weight dependent scaling exponent gamma is
      sufficient to define the mean segmental relaxation time taualpha and its
      distribution. This exponent can be connected to the Gruneisen parameter and
      related thermodynamic quantities, thus demonstrating the interrelationship
      between dynamics and thermodynamics in PMMA. Changes in the relaxation properties
      ("dynamic crossover") are observed as a function of both temperature and
      pressure, with taualpha serving as the control parameter for the crossover. At
      longer taualpha another change in the dynamics is apparent, associated with a
      decoupling of the local segmental process from ionic conductivity.

PMID- 17508829
TI  - Molecular flexibility effects upon liquid dynamics.
AB  - Simulation results for the diffusive behavior of polymer chain/penetrant systems
      are analyzed. The attractive range and flexibility of simple chain molecules were
      varied in order to gauge the effect on dynamics. In all cases, the dimensionless
      diffusion coefficient, D*, is found to be a smooth, single-valued function of the
      packing fraction, eta. The functions D*(eta) are found to be power laws with
      exponents that are sensitive to both chain stiffness and particle type. For a
      specific system type, the D*'s for both penetrant and chain-center-of-mass
      extrapolate to zero at the same packing fraction, eta0. This limiting packing
      fraction is interpreted to be the location of the glass transition, and (eta0
      eta), the distance to the glass transition.

PMID- 17508830
TI  - Ultraviolet photoelectron spectroscopy study of the thermochromic phase
      transition in urethane-substituted polydiacetylenes.
AB  - Threshold solid-state ionization energies determined from ultraviolet
      photoelectron spectra are reported for the thermochromic polydiacetylenes (PDAs)
      from the bis-ethyl- and bis-n-propyl urethanes of 5,7-dodecadiyn-1,12-diol (ETCD
      and PUDO, respectively) and the nonthermochromic 1,6-bis-p-toluenesulfonate of
      2,4-hexadiyne-1,6-diol (PTS) at temperatures above and below the thermochromic
      phase transition. PDA-PTS has an ionization energy of 5.66 eV which does not
      change significantly as the temperature is raised above 140 degrees C. At 25
      degrees C, PDA-ETCD and PDA-PUDO have threshold ionization energies of 5.65 and
      5.51 eV, respectively. The ionization energies of these PDAs increase by
      approximately 0.34 eV as temperature is raised above 140 degrees C and returns to
      the lower values as temperature is reduced to 25 degrees C. The magnitude of the
      increase in ionization energy on heating to temperatures above the thermochromic
      transition is very close to the shift in energy of the electronic spectrum over
      the same temperature range. These observations suggest that the structural
      changes that take place in the course of the thermochromic transition are
      primarily associated with the valence band and are consistent with partial relief
      of mechanical strains.

PMID- 17508831
TI  - Boundary lubricant films under shear: effect of roughness and adhesion.
AB  - The normal interaction and the behavior under shear of mica surfaces covered by
      two different triblock copolymers of polylysine-polydimethysiloxane-polylysine
      were studied by combining the capabilities of the surface forces apparatus and
      the atomic force microscopy. At low pH values these copolymers spontaneously
      adsorb on the negatively charged mica surfaces from aqueous solutions as a
      consequence of the positive charge of the polylysine moieties. The morphology of
      the adsorbed layer is determined by the molecular structure of the particular
      copolymer investigated. This morphology plays a fundamental role on the behavior
      of the adsorbed layers under shear and compression. While nonadhesive smooth
      layers oppose an extremely small resistance to sliding, the presence of
      asperities even at the nanometric scale originates a frictional resistance to the
      motion. The behavior of uniform nonadhesive nanorough surfaces under shear can be
      quantitatively understood in terms of a simple multistable thermally activated
      junction model. The electric charge of the adsorbed copolymer molecules and hence
      the adhesion energy between the coated surfaces can be modified by varying the pH
      of the surrounding media. In the presence of an adhesive interaction between the
      surfaces the behavior under shear is strongly modified. Time-dependent mechanisms
      of energy dissipation have to be evoked in order to explain the changes observed.

PMID- 17508832
TI  - Composition fluctuations, chemical exchange, and nuclear relaxation in membranes
      containing cholesterol.
AB  - A thermodynamic model of cholesterol-phospholipid complexes is used as a starting
      point for calculating fluctuations in membranes containing cholesterol and
      phospholipids. The calculations describe fluctuations in the concentration of
      complexes formed between cholesterol and phospholipids with longer saturated
      fatty acid chains. The fluctuations in complex concentrations arise by two
      distinct mechanisms. In one, the chemical composition of the sample varies from
      point to point, and the concentration of the complexes varies according to local
      chemical equilibrium. In the second, the composition remains fixed, and the
      complexes form and dissociate according to chemical reaction kinetics. In both
      cases the nuclear resonance frequency of a deuterium labeled phospholipid
      undergoes fluctuations and line broadening as a consequence of the formation and
      dissociation of complexes. For a specific ternary lipid mixture at its critical
      composition, deuterium nuclear resonance line broadening of chain labeled
      phospholipids is calculated for temperatures up to 10 degrees -20 degrees above
      the miscibility critical temperature. This line broadening is associated with
      fluctuations in the degree of phospholipid chain ordering related to the
      formation and dissociation of complexes.

PMID- 17508833
TI  - Formation of HO2 radicals from the photodissociation of H2O2 at 248 nm.

PMID- 17508834
TI  - Comment on "melting dynamics of superheated argon: nucleation and growth" [J.
      Chem. Phys. 126, 034505 (2007)].

PMID- 17508838
TI  - Developments in immunization planning in Cambodia--rethinking the culture and
      organization of national program planning.
AB  - INTRODUCTION: As part of its health system reconstruction following decades of
      civil war, Cambodia undertook a program of health sector reform in 1996 to expand
      coverage of essential health services to the population of 14 million, 80% of
      whom are resident in over 13 000 rural villages. During this reform period, one
      of the major national health programs, the National Immunization Program (NIP),
      adapted its planning system to accommodate changes in social and health sector
      structure. AIMS: The aims of this article are to review changes made in the
      approach to national immunization planning and to illustrate how these
      adaptations can help identify future challenges and opportunities for further
      improving immunization coverage in Cambodia. Sources of information for the study
      include immunization plans and data from international and national sources, as
      well as data from the national health information system. Findings of review:
      Management and service delivery reforms undertaken by the NIP include (1)
      strengthening links between immunization, health sector and international health
      planning; (2) development of immunization program multiyear and financial
      sustainability plans; (3) strengthening of national program decision making
      structures and processes; (4) widening of decentralized stakeholder participation
      in health planning; and (5) implementation of service level micro-planning.
      OUTCOMES: These management reforms have been associated with significant
      improvement in public health program performance and outcomes during this period
      (2003-2006). There has been an increase in vaccination coverage for children
      under the age of one year, over a five-year period (increase of 29% for fully
      immunized child at one year of age), with no significant differences in
      vaccination rates between urban and rural areas, and a sharp decrease in the
      incidence of vaccine preventable diseases. CONCLUSION: The NIP is now well
      positioned to take on additional challenges in coming years associated with
      expanding international partnerships, the continued development of civil society,
      further health system decentralization, and the requirement to further improve
      coverage in support of global and regional disease elimination goals. However, as
      costs continue to rise, planners in the future will need to emphasize the
      economic and public health benefits of immunization programs in order to sustain
      increasing levels of national and international investment.

PMID- 17508839
TI  - Effects of 904-nm low-level laser therapy in the management of lateral
      epicondylitis: a randomized controlled trial.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of 904-nm low
      level laser therapy (LLLT) in the management of lateral epicondylitis. BACKGROUND
      DATA: Lateral epicondylitis is characterized by pain and tenderness over the
      lateral elbow, which may also result in reduction in grip strength and impairment
      in physical function. LLLT has been shown effective in its therapeutic effects in
      tissue healing and pain control. METHODS: Thirty-nine patients with lateral
      epicondylitis were randomly assigned to receive either active laser with an
      energy dose of 0.275 J per tender point (laser group) or sham irradiation
      (placebo group) for a total of nine sessions. The outcome measures were
      mechanical pain threshold, maximum grip strength, level of pain at maximum grip
      strength as measured by the Visual Analogue Scale (VAS) and the subjective rating
      of physical function with Disabilities of the Arm, Shoulder and Hand (DASH)
      questionnaire. RESULTS: Significantly greater improvements were shown in all
      outcome measures with the laser group than with the placebo group (p < 0.0125),
      except in the two subsections of DASH. CONCLUSION: This study revealed that LLLT
      in addition to exercise is effective in relieving pain, and in improving the grip
      strength and subjective rating of physical function of patients with lateral
      epicondylitis.

PMID- 17508840
TI  - Low-level laser therapy enhances wound healing in diabetic rats: a comparison of
      different lasers.
AB  - OBJECTIVE: The effects of wound healing acceleration on diabetic rats were
      determined and compared using different laser wavelengths and incident doses.
      BACKGROUND DATA: Many studies have demonstrated that low-level laser therapy
      (LLLT) can promote the wound healing on non-diabetic animals. METHODS: Male
      Sprague-Dawley rats were used. Streptozotocin (70 mg/kg) was applied for diabetes
      induction. An oval full-thickness skin wound was created aseptically with a
      scalpel in 51 diabetic rats and six non-diabetic rats on the shaved back of the
      animals. The study was performed using 532, 633, 810, and 980 nm diode lasers.
      Incident doses of 5, 10, 20, and 30 J/cm(2) and treatment schedule of 3
      times/week were used in the experiments. The area of wound on all rats was
      measured and plotted on a slope chart. The slope values (mm(2)/day), the
      percentage of relative wound healing, and the percentage of wound healing
      acceleration were computed in the study. RESULTS: Mean slope values were 6.0871
      in non-diabetic control and 3.636 in diabetic control rats (p > 0.005). The
      percentages of wound healing acceleration were 15.23, 18.06, 19.54, and 20.39
      with 532-nm laser, 33.53, 38.44, 32.05, and 16.45 with 633-nm laser, 15.72,
      14.94, 9.62, and 7.76 with 810-nm laser, and 12.80, 16.32, 13.79, and 7.74 with
      980-nm laser, using incident doses of 5, 10, 20, and 30 J/cm(2), respectively.
      There were significant differences (p > 0.001) in the mean slope value of wound
      healing on diabetic rats between control groups and treatment groups in 532, 633,
      810, and 980 nm lasers. CONCLUSION: The wound healing on control rats with
      diabetes was slower than on control rats without diabetes. LLLT at appropriate
      treatment parameters can enhance the wound healing on diabetic rats. The optimum
      wavelength was 633 nm, and the optimum incident dose was 10 J/cm(2) in our study.

PMID- 17508841
TI  - In vitro exposure of wounded diabetic fibroblast cells to a helium-neon laser at
      5 and 16 J/cm2.
AB  - OBJECTIVE: The aim of the present investigation was to assess morphological,
      cellular, and molecular effects of exposing wounded diabetic fibroblast cells to
      He-Ne (632.8 nm) laser irradiation at two different doses. BACKGROUND DATA: An
      alternative treatment modality for diabetic wound healing includes low-level
      laser therapy (LLLT). Although it's used in many countries and for many medical
      conditions, too many health care workers are unaware of this therapy, and there
      is still controversy surrounding its effectiveness. METHODS: Normal human skin
      fibroblast cells (WS1) were used to simulate a wounded diabetic model. The effect
      of LLLT (632.8 nm, 5 and 16 J/cm(2) once a day on two non-consecutive days) was
      determined by analysis of cell morphology, cytotoxicity, apoptosis, and DNA
      damage. RESULTS: Cells exposed to 5 J/cm(2) showed a higher rate of migration
      than cells exposed to 16 J/cm(2), and there was complete wound closure by day 4.
      Exposure of WS1 cells to 5 J/cm(2) on two non-consecutive days did not induce
      additional cytotoxicity or genetic damage, whereas exposure to 16 J/cm(2) did.
      There was a significant increase in apoptosis in exposed cells as compared to
      unexposed cells. CONCLUSION: Based on cellular morphology, exposure to 5 J/cm(2)
      was stimulatory to cellular migration, whereas exposure to 16 J/cm(2) was
      inhibitory. Exposure to 16 J/cm(2) induced genetic damage on WS1 cells when
      exposed to a He-Ne laser in vitro, whereas exposure to 5 J/cm(2) did not induce
      any additional damage.

PMID- 17508842
TI  - In vitro evaluation of enamel demineralization after Er:YAG and Nd:YAG laser
      irradiation on primary teeth.
AB  - OBJECTIVE: This in vitro study evaluated the influence of both Er:YAG and Nd:YAG
      laser irradiation on deciduous enamel demineralization. BACKGROUND DATA: Although
      there are still few studies on the use of the high-intensity laser for caries
      prevention in deciduous teeth, it is believed that its use on the dental
      structure can lead to a more acid-resistant surface. METHODS: Forty enamel
      samples obtained from 22 deciduous first molar teeth were ground and randomly
      divided into four groups (n = 10): group 1 (G1), no treatment (negative control);
      G2, fluoride (positive control); G3, Er:YAG laser (2 Hz, 60 mJ, 40.3 J/cm(2));
      G4, Nd:YAG laser (80 mJ, 10 Hz, 0.8 W). After the surface treatment, the samples
      were submitted to an acid challenge that consisted of a 5-day immersion in
      demineralizing (3 h) and remineralizing solution (21 h). Next, a microhardness
      test was preformed. RESULTS: Analysis of variance (ANOVA) and Student Newman
      Keuls tests were performed (alpha = 5%). The percentage of lesion inhibition for
      each group was as follows: G2, 59.4%; G3, 35.7%; and G4, 40.4%. As regards the
      percentage loss of mineral volume, there was no statistical difference between
      groups G2 (444.37 +/- 146.42) and G3 (441.81 +/- 207.08) when compared with group
      G1 (281.03 +/- 134.57). All experimental groups presented a lower mineral loss
      compared with the non-irradiated samples (G4). CONCLUSION: The findings of the
      present study revealed that both Nd:YAG and Er:YAG lasers can be an alternative
      tool for enhancing deciduous enamel acid resistance.

PMID- 17508843
TI  - Effects of KTP laser irradiation, diode laser, and LED on tooth bleaching: a
      comparative study.
AB  - OBJECTIVE: This in vitro study examines the whitening efficacy of a light
      emitting diode (LED), a diode laser, and a KTP laser irradiation in dental
      bleaching by analyzing the change in color achieved from the treatment, the
      temperature increase induced in the pulpal cavity, as well as enamel
      microhardness measurement after treatment. BACKGROUND DATA: Bleaching techniques
      achieved significant advances with the use of coherent or incoherent radiation
      sources to activate the bleaching agents. METHODS: A hydrogen peroxide bleaching
      agent, Hi-Lite, was stimulated with an LED, a 980-nm diode laser at 0.8 W, or a
      532-nm KTP laser at 1.0 W for 30 sec on 64 extracted human incisors. During
      irradiation, the temperature in the pulpal cavity was monitored. The color change
      was evaluated using the CIE L*a*b* color space measurement system, and Vikers
      enamel microhardness was tested after treatment. RESULTS: A mean total color
      difference value (DeltaE*) greater than 5.0 was obtained in each group. KTP-laser
      induced bleaching gave a significantly higher DeltaL* (8.35) after treatment (p <
      0.01). Neither LED nor the two lasers produced significant differences in the
      enamel microhardness after treatment (p > 0.01). Mean maximal pulpal temperature
      rise was 2.95 degrees C for LED, 3.76 degrees C for KTP laser, and 7.72 degrees C
      for diode laser, respectively. CONCLUSION: The results of this study suggest that
      KTP laser is effective at providing brighter teeth. According to the conditions
      used in this study, the LED and KTP laser induced a safer pulpal temperature
      increase when assisted with Hi-Lite bleaching gel.

PMID- 17508844
TI  - Infrared laser photobiomodulation (lambda 830 nm) on bone tissue around dental
      implants: a Raman spectroscopy and scanning electronic microscopy study in
      rabbits.
AB  - OBJECTIVE: The aim of this study was to assess, through Raman spectroscopy, the
      incorporation of calcium hydroxyapatite (CHA; approximately 960 cm(1)), and
      scanning electron microscopy (SEM), the bone quality on the healing bone around
      dental implants after laser photobiomodulation (lambda830 nm). BACKGROUND DATA:
      Laser photobiomodulation has been successfully used to improve bone quality
      around dental implants, allowing early wearing of prostheses. METHODS: Fourteen
      rabbits received a titanium implant on the tibia; eight of them were irradiated
      with lambda830 nm laser (seven sessions at 48-h intervals, 21.5 J/cm(2) per
      point, 10 mW, phi approximately 0.0028 cm(2), 86 J per session), and six acted as
      control. The animals were sacrificed 15, 30, and 45 days after surgery. Specimens
      were routinely prepared for Raman spectroscopy and SEM. Eight readings were taken
      on the bone around the implant. RESULTS: The results showed significant
      differences on the concentration of CHA on irradiated and control specimens at
      both 30 and 45 days after surgery (p < 0.001). CONCLUSION: It is concluded that
      infrared laser photobiomodulation does improve bone healing, and this may be
      safely assessed by Raman spectroscopy or SEM.

PMID- 17508845
TI  - Photobiomodulation on the angiogenesis of skin wounds in rats using different
      light sources.
AB  - OBJECTIVE: The aim of this study was to compare the angiogenic effects of laser
      and light-emitting diode (LED) illumination on wounds induced in rats, with
      varied fluence. BACKGROUND DATA: The LED is an alternative light source that
      accelerates wound healing, and its efficiency concerning the angiogenic effect
      was compared to low-level laser therapy (LLLT). METHODS: The experimental model
      consisted of a circular wound inflicted on the quadriceps of 120 rats, using a 15
      mm-diameter "punch." Animals were divided randomly into five groups: two groups
      of laser, with dosages of 5 and 20 J/cm(2), respectively, two groups of LED, also
      with dosages of 5 and 20 J/cm(2), and a control group. Six hours after wound
      infliction, the treated groups received the diverse applications accordingly and
      were irradiated every 24 h. Angiogenesis was studied through histomorphometry on
      days 3, 7, 14, and 21 after the wounds were inflicted. RESULTS: On days 3, 7, and
      14, the proliferation of blood vessels in all irradiated groups was superior in
      comparison to those of the control group (p < 0.05). Treatment with fluence of 5
      J/cm(2) was better than the laser group with 20 J/cm(2) on day 21. CONCLUSION:
      Red LLLT and LED demonstrated expressive results in angiogenesis. Light coherence
      was shown not to be essential to angiogenesis. However, further studies are
      needed in order to investigate the photobiomodulatory effects of LED in relation
      to LLLT in various biological tissues.

PMID- 17508846
TI  - Promotion of regenerative processes in injured peripheral nerve induced by low
      level laser therapy.
AB  - OBJECTIVE: This study aimed to assess in vitro the influence of low-level laser
      therapy (LLLT) on the regenerative processes of a peripheral nerve after trauma.
      BACKGROUND DATA: In peripheral nerve injury initiated after severing due to
      accident or by a surgeon during operation, photomodulation by light in the red to
      near-infrared range (530-1000 nm) using low-energy lasers has been shown to
      accelerate nerve regeneration. METHOD: Twenty-four New Zealand adult male rabbits
      were randomly assigned to two equal groups (control and laser-treated). General
      anesthesia was administered intramuscularly, and exploration of the peroneal
      nerve was done in the lateral aspect of the left leg. Complete section of the
      nerve was performed, which was followed by suturing of the neural sheath
      (epineurium). Irradiation was carried out directly after the operation and for 10
      consecutive days. The laser used was diode with wavelength of 901 nm (impulsive)
      and power of 10 mW; it was a square-shaped window type (16 cm(2)), and its energy
      was applied by direct contact of the instrument's window to the site of the
      operation. Three rabbits from each group were sacrificed at the end of weeks 2,
      4, 6, and 8, and specimens were collected from the site of nerve suturing and
      sent for histopathological examination. RESULTS: Two important factors were
      examined via histopathology: diameter of the nerve fibers and individual
      internodal length. Compared to the control group, significant variations in
      regeneration were observed, including thicker nerve fibers, more regular myelin
      layers, clearer nodes of Ranvier with absence of short nodes in the treated
      group. Variations between the two groups for diameter were significant for the
      2(nd) week (p < 0.05), highly significant for the 4(th) and 6(th) weeks,
      respectively (p < 0.01), and very highly significant for the 8(th) week (p <
      0.001). Variations between the two groups for internodal length were highly
      significant for the 2(nd) and 4(th) weeks (p < 0.01), and very highly significant
      for the 6(th) and 8(th) weeks (p < 0.001). CONCLUSION: This experiment affirms
      the beneficial effect of LLLT on nerve regeneration, since LLLT produced a
      significant amount of structural and cellular change. The results of the present
      study suggest that laser therapy may be a viable approach for nerve regeneration,
      which may be of clinical relevance in scheduled surgery or microsurgery.

PMID- 17508847
TI  - Effect of low-level laser therapy on hemorrhagic lesions induced by immune
      complex in rat lungs.
AB  - OBJECTIVE: The aim of this study was to investigate if low-level laser therapy
      (LLLT) can modulate formation of hemorrhagic lesions induced by immune complex.
      BACKGROUND DATA: There is a lack of information on LLLT effects in hemorrhagic
      injuries of high perfusion organs, and the relative efficacy of LLLT compared to
      anti-inflammatory drugs. METHODS: A controlled animal study was undertaken with
      49 male Wistar rats randomly divided into seven groups. Bovine serum albumin
      (BSA) i.v. was injected through the trachea to induce an immune complex lung
      injury. The study compared the effect of irradiation by a 650-nm Ga-Al-As laser
      with LLLT doses of 2.6 Joules/cm(2) to celecoxib, dexamethasone, and control
      groups for hemorrhagic index (HI) and myeloperoxide activity (MPO) at 24 h after
      injury. RESULTS: The HI for the control group was 4.0 (95% CI, 3.7-4.3).
      Celecoxib, LLLT, and dexamethasone all induced significantly (p < 0.01) lower HI
      than control animals at 2.5 (95% CI, 1.9-3.1), 1.8 (95% CI, 1.2-2.4), and 1.5
      (95% CI, 0.9-2.1), respectively, for all comparisons to control. Dexamethasone,
      but not celecoxib, induced a slightly, but significantly lower HI than LLLT (p =
      0.04). MPO activity was significantly decreased in groups receiving celecoxib at
      0.87 (95% CI, 0.63-1.11), dexamethasone at 0.50 (95% CI, 0.24-0.76), and LLLT at
      0.7 (95% CI, 0.44-0.96) when compared to the control group, at 1.6 (95% CI, 1.34
      1.96; p < 0.01), but there were no significant differences between any of the
      active treatments. CONCLUSION: LLLT at a dose of 2.6 Joules/cm(2) induces a
      reduction of HI levels and MPO activity in hemorrhagic injury that is not
      significantly different from celecoxib. Dexamethasone is slightly more effective
      than LLLT in reducing HI, but not MPO activity.

PMID- 17508848
TI  - Effect of surface conditioning on adhesion of glass ionomer cement to Er,Cr:YSGG
      laser-irradiated human dentin.
AB  - OBJECTIVE: This study aimed to show the effect of dentin conditioner on the bond
      strength of glass ionomer cement to Er,Cr:YSGG-laser-irradiated dentin compared
      to conventional bur-prepared dentin. BACKGROUND DATA: Glass ionomer cement bonds
      to tooth structure via direct chemical bonding without using any adhesive system.
      To improve the adhesion of this material, pretreating the dentin surface with a
      conditioner is recommended. Recently, lasers for tooth drilling have been used
      for cavity preparation, especially the Er,Cr:YSGG laser. However, there is a lack
      of research on the bond strength of glass ionomer cement to conditioned
      Er,Cr:YSGG-laser-irradiated dentin. METHODS: Extracted human teeth were divided
      into eight experimental groups and prepared by using either Er,Cr:YSGG laser or a
      conventional bur. In half of these two groups, the relevant conditioner was
      applied on the dentin before building up with glass-ionomer cement. After 24 h,
      all teeth were sectioned, and the microtensile bond strength was determined. The
      mode of failure was observed, and the fractured surfaces were examined by
      scanning electron microscopy (SEM). RESULTS: The use of conditioner was found to
      significantly affect bond strength for laser-prepared samples (analysis of
      variance [ANOVA], p < 0.05). Failure analysis showed no adhesive failures in the
      laser-prepared teeth, and this suggests an effective bond between glass ionomer
      cement and Er,Cr:YSGG laser-cut dentin. CONCLUSION: To obtain the maximum
      retention of a glass ionomer restoration to Er,Cr:YSGG laser-irradiated dentin,
      the results of this study confirm that pretreatment of the laser-prepared dentin
      with dentin conditioner is advantageous.

PMID- 17508849
TI  - Scanning electron microscopic analysis of diode laser-treated titanium implant
      surfaces.
AB  - OBJECTIVE: The objective of this study was to analyze the possible morphological
      alterations of the surface implants after using 980-nm diode laser irradiation
      (InGalAsP) at various energies. BACKGROUND DATA: Laser-based protocols have been
      proposed for decontaminating dental implant surfaces when treating peri
      implantitis, although few studies have addressed this topic directly. METHODS:
      Five smooth surface implants (TiOblast ST, Astra Tech AB, Molndal, Sweden) were
      irradiated with 980-nm diode laser, and one implant that was not lased served as
      the control. The surface of each implant was treated for 60 sec on implant neck
      to apical threads. The experiment consisted of exposing the dental titanium
      implants to diode laser irradiation. Then the surfaces were analyzed by scanning
      electron microscopy (SEM). RESULTS: SEM analysis demonstrated any damage or
      alteration of titanium surfaces. Regardless of the power setting, there was no
      visible difference between lased and non-lased titanium surfaces after
      irradiation with the 980-nm diode laser. CONCLUSION: The results of this study
      suggest that the InGalAsP diode laser (980 nm) does not damage titanium surfaces,
      and seems to be safe and useful of treating peri-implantitis, irrespective of
      power output.

PMID- 17508851
TI  - An ode to the CO2 laser.

PMID- 17508850
TI  - Single-cell analysis of protein kinase C activation during anti-apoptosis and
      apoptosis induced by laser irradiation.

PMID- 17508897
TI  - Lymphatics and the heart: the importance of visceral lymphatic function in health
      and disease.

PMID- 17508898
TI  - The primary valves in the initial lymphatics during inflammation.
AB  - BACKGROUND: The primary valve system in the initial lymphatics prevents fluid
      transport from the initial lymphatics back into the interstitium. The authors
      hypothesize that since the primary valves are made up of an extraordinarily thin
      endothelium, they are readily compromised by mechanical or biochemical
      inflammatory stimuli. Thus, the opening dimension of the primary valves and their
      ability to prevent reflux into the interstitium during inflammation were
      investigated. METHODS AND RESULTS: Acute inflammation was generated in the intact
      rat spinotrapezius muscle by suffusion of f-Met-Leu-Phe and platelet-activating
      factor. Once inflamed, the effective opening dimensions of the primary valves and
      the transport back out of the initial lymphatics were determined by examining the
      transport of fluorescent tracers from the interstitium to the lymphatics. Quantum
      dots and fluorescently labeled albumin readily enter initial lymphatics from the
      interstitium. The maximum diameter of microspheres that enter the initial
      lymphatics is between 0.5 microm and 0.8 microm in both control and inflamed
      tissue. While under control conditions no quantum dots escaped from initial
      lymphatics back into the interstitium, during inflammation there was extensive
      escape of quantum dots. CONCLUSIONS: These results suggest that, in acute
      inflammation, the function of the endothelial barriers in the initial lymphatics
      may be compromised. A failure of the primary lymphatic valves has two
      consequences. First, fluid clearance from the tissue is less efficient, which
      causes the level of edema to increase. Second, the leaking initial lymphatics
      allow inflammatory mediators to accumulate in the tissue, therefore enhancing
      interstitial and lymphatic inflammatory reactions.

PMID- 17508899
TI  - Optical monitoring of microlymphatic disturbances during experimental lymphedema.
AB  - BACKGROUND: Rat mesentery has been widely used to study microvascular functions.
      The goal of this work is to extend this animal model to monitor blood and lymph
      microvessel function during lymphedema. METHODS AND RESULTS: Lymphedema is
      created by microsurgical removal of regional lymph nodes (lymphadenectomy) or
      ligation of the collecting vein. Water volume in mesenteric tissue, microvessel
      diameters, phasic contraction, valve function, lymph flow velocity, and cell
      migration were analyzed during lymphedema development. Dynamic observation of
      water amount after lymphadenectomy revealed increasing edema from 30 min to 1
      week; greatest degree of edema at one week, and gradual decrease in edema from 1
      to 11 weeks. These effects were accompanied by acute constriction of lymph
      vessels and slowing of lymph flow velocity, switching to dilation and appearance
      of new blood capillaries at week 1, progressing to dilation and degenerative
      changes of the microlymphatic wall at week 4, and, finally, leading to lymphatic
      fibrosis and lymphangiogenesis at week 11. Acute venous insufficiency (30 min
      after vein ligation) led to significant edema, decreasing blood flow velocity to
      stasis, and output of erythrocytes from venules to interstitium, with further
      movement to microlymphatics and regional lymph nodes. CONCLUSIONS: Rat mesentery
      as an animal model in combination with an advanced optical imaging system is
      valuable in studying microlymphatic disturbances in mesentery during the
      development of experimental lymphedema from latent period to chronic stages,
      including monitoring of individual cell dislocation with high resolution optical
      imaging.

PMID- 17508900
TI  - Spontaneous electrical activity in sheep mesenteric lymphatics.
AB  - BACKGROUND: It has recently become apparent that the lymph pump is an electrical
      entity that rivals the heart in complexity. Many interesting currents have been
      demonstrated by voltage clamping isolated lymphatic smooth muscle cells, but
      until now the role of these currents in the intact syncitium has not been
      studied. METHODS AND RESULTS: Intracellular microelectrode recordings were made
      from smooth muscle of sheep mesenteric lymphatics to investigate the
      electrophysiological basis of lymphatic pumping. Approximately 50% of the vessels
      exhibited spontaneous electrical activity, varying from regular oscillations in
      membrane potential to spike complexes. Spike complexes generally consisted of one
      or more action potentials superimposed on a slower depolarization or 'plateau'
      phase and were often preceded by a slow diastolic depolarization or 'pre
      potential'. Norepinephrine (5 microM) induced depolarizing events in quiescent
      preparations. Both agonist-induced oscillations and spike complexes were
      attenuated or completely abolished by 2-aminoethoxydiphenyl borate (2-APB); 10
      100 microM). Cesium (1 mM) reduced the frequency of spontaneous firing by
      approximately 30% by flattening the pre-potential phase. In addition to having a
      negative inotropic effect, 10 mM Cs(+) also caused gradual membrane
      depolarization and prolonged the plateau. 1 microM nifedipine abolished
      spontaneous events while tetrodotoxin (TTX; 0.5-1 muM) decreased the amplitude
      and maximum dV/dt of the spike upstroke or stopped activity completely.
      Spontaneously active segments of lymphatic vessel were inhibited by the chloride
      channel blocker, anthracene-9-carboxylic acid (9-AC; 250 microM - 1 mM)
      suggesting that I(Cl(Ca)) plays a significant role in the generation of
      spontaneous activity in this tissue. Penitrem-A (0.1 microM) did not affect
      resting membrane potential but increased action potential amplitude and prolonged
      the plateau, suggesting that calcium-activated potassium current does not make a
      significant contribution to resting membrane conductance but is important in
      membrane repolarization following calcium influx during the action potential. In
      contrast 4-aminopyridine (4-AP; 5 microM) caused significant membrane
      depolarization, suggesting the existence of an active 4-AP-sensitive current at
      rest. CONCLUSIONS: These results demonstrate that the currents found in isolated
      voltage-clamped cells from sheep mesenteric lymphatics do play a significant role
      in the shaping of spontaneous electrical activity of the intact syncitium.

PMID- 17508901
TI  - Cardiac lymphatic interruption is a major cause for allograft failure after
      cardiac transplantation.
AB  - Cardiac transplantation is one of the most effective treatments of end stage
      heart failure to date, although it comes with risks. One of the major
      complications of cardiac transplantation is allograft failure, which is caused by
      ischemic injuries, pulmonary hypertension and chronic rejection. Recent animal
      and human studies have demonstrated that cardiac lymphatic obstruction leads to
      significant myocardial fibrosis and depression in contractile forces. We
      hypothesize that lymphatic interruption, which is almost inevitable after cardiac
      transplantation, is a major cause of cardiac allograft failure through direct
      damages to the myocardium and also through the formation of allograft coronary
      vasculopathy.

PMID- 17508902
TI  - Literature watch. Blood and lymphatic endothelial cell-specific differentiation
      programs are stringently controlled by the tissue environment.

PMID- 17508906
TI  - From selenium to selenoproteins: synthesis, identity, and their role in human
      health.
AB  - The requirement of the trace element selenium for life and its beneficial role in
      human health has been known for several decades. This is attributed to low
      molecular weight selenium compounds, as well as to its presence within at least
      25 proteins, named selenoproteins, in the form of the amino acid selenocysteine
      (Sec). Incorporation of Sec into selenoproteins employs a unique mechanism that
      involves decoding of the UGA codon. This process requires multiple features such
      as the selenocysteine insertion sequence (SECIS) element and several protein
      factors including a specific elongation factor EFSec and the SECIS binding
      protein 2, SBP2. The function of most selenoproteins is currently unknown;
      however, thioredoxin reductases (TrxR), glutathione peroxidases (GPx) and thyroid
      hormone deiodinases (DIO) are well characterised selenoproteins involved in redox
      regulation of intracellular signalling, redox homeostasis and thyroid hormone
      metabolism. Recent evidence points to a role for selenium compounds as well as
      selenoproteins in the prevention of some forms of cancer. A number of clinical
      trials are either underway or being planned to examine the effects of selenium on
      cancer incidence. In this review we describe some of the recent progress in our
      understanding of the mechanism of selenoprotein synthesis, the role of
      selenoproteins in human health and disease and the therapeutic potential of some
      of these proteins.

PMID- 17508907
TI  - Selective oxidative stress in cell nuclei by nuclear-targeted D-amino acid
      oxidase.
AB  - The effects of nuclear-localized oxidative stress on both nuclear antioxidant
      systems, and the processes that they regulate, are not clearly understood. Here,
      we targeted a hydrogen peroxide (H(2)O(2))-producing enzyme, D-amino acid oxidase
      (DAAO), to the nucleus (NLS-DAAO) and used this to generate H(2)O(2) in the
      nuclei of cells. On addition of N-acetyl-D-alanine (NADA), a substrate of DAAO,
      to NLS-DAAO-transfected HeLa cells, a twofold increase in ROS production relative
      to untreated, transfected control was observed. Staining of cellular thiols
      confirmed that NLS-DAAO-induced ROS selectively modified the nuclear thiol pool,
      whereas the cytoplasmic pool remained unchanged. Furthermore, NLS-DAAO/NADA
      induced ROS caused significant oxidation of the nuclear GSH pool, as measured by
      nuclear protein S-glutathionylation (Pr-SSG), but under the same conditions,
      nuclear Trx1 redox state was not altered significantly. NF-kappaB reporter
      activity was diminished by NLS-DAAO/NADA-stimulated nuclear oxidation. We
      conclude that nuclear GSH is more susceptible to localized oxidation than is
      nuclear Trx1. Furthermore, the attenuation of NF-kappaB reporter activity in the
      absence of nuclear Trx1 oxidation suggests that critical nuclear redox proteins
      are subject to control by S-glutathionylation during oxidative stress in the
      nucleus.

PMID- 17508908
TI  - Acid sphingomyelinase and its redox amplification in formation of lipid raft
      redox signaling platforms in endothelial cells.
AB  - This study examined the role of acid sphingomyelinase (ASM) and its redox
      amplification in mediating the formation of lipid raft (LR) redox signaling
      platforms in coronary arterial endothelial cells (CAECs). Using small
      interference RNA (siRNA) of ASM, Fas ligand (FasL)-induced increase in ASM
      activity, production of ceramide, and LR clustering in CAECs were blocked, and
      clustered Fas was also substantially reduced in detergent-resistant membrane
      fractions of CAECs. LR clustering, gp91(phox) aggregation, and p47(phox)
      translocation to the LR clusters induced by FasL were also blocked in ASM-siRNA
      transfected CAECs. Corresponding to this reduction of LR clustering with NAD(P)H
      oxidase subunits in ASM-siRNA transfected CAECs, superoxide (O(2)(-*)) production
      was significantly decreased as measured by either ESR or fluorescent
      spectrometry. Interestingly, superoxide dismutase (SOD) not only scavenged (O(2)(
      *)), but also markedly attenuated LR clustering. Xanthine/xanthine oxidase, an
      exogenous (O(2)(-*)) generating system, dramatically increased ASM activity and
      LR clustering in EC membrane and enhanced FasL-induced LR clustering, which were
      blocked by SOD. These results suggest that that ASM activates LR clustering to
      form redox signaling platforms, where (O(2)(-*)) production enhances ASM
      activity, and thereby results in a forwarding amplification of LR and redox
      signaling. This ASM-mediated feedforwarding mechanism may be critical for an
      efficient transmembrane signaling through LRs.

PMID- 17508909
TI  - Nitric oxide regulation of microvascular oxygen.
AB  - The role of nitric oxide (NO) as a highly diffusible free radical gaseous
      vasodilator is intrinsically linked to the control of blood flow and oxygen
      (O(2)) delivery to tissue. NO also is involved in regulating mitochondrial O(2)
      metabolism, growth of new blood vessels, and blood oxygenation through control of
      respiratory ventilation. Hemoglobin and myoglobin may help to conserve NO for
      subsequent release of a NO-related vasoactive species under hypoxic conditions.
      NO has a major role in regulating microvascular O(2), and dysfunctional NO
      signaling is associated with the pathogenesis of metabolic and cardiovascular
      diseases.

PMID- 17508910
TI  - Time-dependant oxygen partial pressure in capillaries and tissue in the hamster
      window chamber model.
AB  - The possibility of a plasma oxygen diffusion barrier implies a significant
      resistance to oxygen diffusion and the existence of capillary erythrocyte
      associated transients of oxygen. This effect was analyzed by measuring
      intracapillary blood and tissue pO(2) in the hamster chamber window model using a
      noninvasive intravital microscopy palladium porphyrin phosphorescence decay
      technique for two set light excitations (high and low). Using high light
      excitation, intracapillary blood pO(2) was 13.7 +/- 6.1 mm Hg, and increased to
      18.0 +/- 4.5 mm Hg for low light excitation. For high light excitation,
      intracapillary blood pO(2) peaks were in the range of 25-30 mm Hg, and the lowest
      values were in the range of 5-10 mm Hg. Reducing the excitation provided a more
      uniform pO(2) ranging 15-25 mm Hg. With temporal reduction in blood capillary
      pO(2), levels were correlated to the increase in phosphorescent amplitude that
      corresponded to plasma gaps. Tissue pO(2) measured at low light excitation in the
      proximity of capillaries was 23.1 +/- 1.8 mm Hg. In conclusion, low
      intracapillary blood pO(2) measurements at full hematocrit are an artifact, only
      observed when oxygen consumption by the measurement technique was excessive
      and/or absorption of the excitation light was increased by the absence of RBCs.
      These findings suggest that resistance to oxygen diffusion in plasma is a minor
      factor in tissue oxygenation by capillaries in the hamster model.

PMID- 17508911
TI  - Interdiction of the diabetic state in NOD mice by sustained induction of heme
      oxygenase: possible role of carbon monoxide and bilirubin.
AB  - The aims of the present study were to assess whether sustained HO-1 expression
      could moderate or prevent diabetes in an animal model of the disease and, if so,
      to examine the possible mechanisms involved. Our results showed that HO-1
      expression and HO activity were upregulated in the pancreas of non-obese diabetic
      (NOD) mice by the weekly administration of cobalt protoporphyrin (CoPP). Blood
      glucose levels in CoPPtreated mice decreased to normal, but continuously
      increased in untreated controls. Beta-cell numbers were preserved in the islets
      of CoPP-treated mice, whereas no beta cells were found in untreated diabetic
      mice. The number of CD11c(+) dendritic cells was significantly decreased in the
      pancreas of CoPP-treated NOD mice, but this effect was reversed by the inhibition
      of HO activity. Increased levels of HO-1 produced a new pancreatic phenotype, as
      reflected by increases in phosphorylated AKT, BcL-xL and RSK levels, and
      decreases in O(2)- and 3-NT levels. These novel findings provide a link between
      the increase in HO-1 activity, with its concurrent enhanced production of carbon
      monoxide (CO) and bilirubin, a decrease in infiltrated CD11c(+) dendritic cells
      and an increase in anti-apoptotic proteins, including RSK and BcL-xL, in the
      interdiction of the diabetic state.

PMID- 17508912
TI  - Angiotensin II Type 1 receptor antagonism mediates uncoupling protein 2-driven
      oxidative stress and ameliorates pancreatic islet beta-cell function in young
      Type 2 diabetic mice.
AB  - We recently identified a local pancreatic islet renin-angiotensin system (RAS),
      and demonstrated that it is upregulated in an animal model of obesity-induced
      type 2 diabetes mellitus (T2DM). Moreover, angiotensin II type 1 receptor (AT1R)
      antagonism improves beta-cell function and glucose tolerance in young T2DM mice
      and delays the onset of diabetes. Meanwhile, obesity-induced T2DM results in
      oxidative stress-mediated activation of uncoupling protein 2 (UCP2), a negative
      regulator of islet function. In the present study, we postulated that some of the
      protective effects of AT1R antagonism might be mediated through interference with
      this pathway and tested this hypothesis in a T2DM animal model. Losartan, an AT1R
      antagonist, was given to 4-week-old obese db/db mice for a period of 8 weeks.
      UCP2-driven oxidative damage and apoptosis were then analyzed in isolated islets.
      Losartan selectively inhibited oxidative stress via downregulation of NADPH
      oxidase; this in turn suppressed UCP2 expression, thus improving beta-cell
      insulin secretion and decreasing apoptosis-induced beta-cell mass loss in db/db
      mouse islets. These data indicate that islet AT1R activation in young diabetic
      mice can generate progressive islet beta-cell failure through UCP-driven
      oxidative damage.

PMID- 17508913
TI  - Oxidant stress, immune dysregulation, and vascular function in type I diabetes.
AB  - Although high glucose is an important contributor to diabetic vasculopathies,
      complications still occur in spite of tight glycemic control, suggesting that
      some critical event prior to or concurrent with hyperglycemia may contribute to
      early vascular changes. Utilizing previously published and new experimental
      evidence, this review will discuss how prior to the hyperglycemic state, an
      imbalance between oxidants and antioxidants may contribute to early vascular
      dysfunction and set in motion proinflammatory insults that are further amplified
      as the diabetes develops. This imbalance results from the resetting of the
      equilibrium between vessel superoxide/H(2)O(2) production and/or decreased
      antioxidant defenses. Such an imbalance may cause endothelial dysfunction,
      characterized by abnormal endothelium-dependent vasoreactivity, as the first sign
      of blood vessel damage, followed by morphological changes of the vessel wall and
      inflammation. As such, increased oxidant stress in preglycemic states may be a
      critically central initiating event that underlies the pathogenesis of life
      threatening vascular diseases in autoimmune diabetes. This review focuses on the
      relationship between oxidative stress, immune dysregulation, and vascular injury
      in type 1 diabetes, and how the discovery of novel pathways of vascular disease
      in nonobese diabetic mice may direct future studies in patients with type 1
      diabetes.

PMID- 17508914
TI  - Oxidative stress, glucose metabolism, and the prevention of type 2 diabetes:
      pathophysiological insights.
AB  - With the rising epidemic of type 2 diabetes worldwide, including the United
      States, the death and disability due to the suboptimal control of cardiovascular
      disease associated with this epidemic has made prevention of type 2 diabetes
      emerge as a primary strategic intervention. Several modalities have been assessed
      in large randomized controlled trials for diabetes prevention such as lifestyle
      interventions and various pharmacologic agents. Included in these agents are
      metformin, thiazolidinediones, acarbose, angiotensin converting enzyme
      inhibitors, as well as angiotensin receptor blockers. Abrogation of oxidative
      stress appears to be a common soil hypothesis that explains the favorable effects
      of these agents on glucose metabolism, including the prevention of diabetes and
      its complications. This comprehensive review highlights the role of oxidative
      stress in the pathogenesis of diabetes, with emphasis on the major clinical
      trials conducted on prevention of type 2 diabetes.

PMID- 17508915
TI  - Pyridine nucleotide redox abnormalities in diabetes.
AB  - In addition to hyperglycemia, diabetes is associated with increased levels of
      circulating free fatty acids, lactate, and branched chain amino acids, all of
      which produce an excessive reduced form of pyridine nucleotides NADH (reductive
      stress) in the cytosol and mitochondria. Our studies suggest that cytosolic NADH
      reductive stress under high glucose is largely caused by increased flux of
      glucose through polyol (sorbitol) pathway consisting of aldose reductase and
      sorbitol dehydrogenase. Inhibition of aldose reductase that blocks the polyol
      pathway has been shown to ameliorate diabetic neuropathy in humans. Cytosolic
      NADH reductive stress is predicted to increase production of diglycerides,
      reactive oxygen species, and methylglyoxal. Recent studies indicate that
      increasing NADH affects gene expression through the NADH activating
      transcriptional co-repressor, C-terminal binding protein (CtBP). In addition, it
      has been shown that the NADH utilizing enzyme, glyceraldehyde-3-phosphate
      dehydrogenase, participates as transcriptional regulator. These findings testify
      to the importance of NADH redox balance in cell biology and pathogenesis of
      diabetes and its complications. For example, through CtBP, the high NADH to
      NAD(+) ratio decreases an expression of SirT1, the protein inducing longevity and
      anti-apoptosis. This review covers metabolic cascades causing reductive stress
      and oxidative stress in diabetes after a brief introduction of the redox concept.

PMID- 17508916
TI  - The expanding role of oxidative stress, renin angiotensin system, and beta-cell
      dysfunction in the cardiometabolic syndrome and Type 2 diabetes mellitus.
AB  - The incidence of obesity, cardiometabolic syndrome (CMS), and type 2 diabetes
      mellitus (DM2), as well as their devastating cardiovascular consequences, keep
      rising with increasing human and economical costs. For a long time, insulin
      resistance has been the main player in the pathogenesis and treatment of DM2, but
      every day more knowledge is gained about the central role of beta-cell failure,
      not only in the appearance of hyperglycemia but also in the failure of the
      pharmacological therapy. beta-Cell failure implies impairment of
      glucosestimulated insulin secretion and loss of beta-cell mass. Hyperglycemia,
      elevated circulating fatty acids, inadequate local activation of renin
      angiotensin system, and chronic low grade inflammation are conditions that
      coexist in the CMS and DM2 that turn out to be deleterious for the beta-cell
      functioning and existance. Excessive oxidative stress secondary to increased
      production of reactive oxygen species and decreased availability of antioxidants
      is a possible common converging point of the multiple noxious stimuli. Activation
      of the NADPH oxidase complex secondary to angiotensin II stimulation is of
      interest, as its pharmacological blockade has beneficial effects. New knowledge
      about the intimate mechanisms of oxidative-stress induced beta-cell failure will
      provide new therapeutic targets against CMS and DM2.

PMID- 17508917
TI  - Mechanisms for oxidative stress in diabetic cardiovascular disease.
AB  - Obesity, metabolic syndrome, and diabetes are increasingly prevalent in Western
      society, and they markedly increase the risk for atherosclerotic vascular
      disease, the major cause of death in diabetics. Although recent evidence suggests
      a causal role for oxidative stress in insulin resistance, diabetes, and
      atherosclerosis, there is considerable controversy regarding its nature,
      magnitude, and underlying mechanisms. Glucose promotes glycoxidation reactions in
      vitro, and products of glycoxidation and lipoxidation are elevated in plasma and
      tissue from humans suffering from diabetes, but the exact relationships between
      hyperglycemia and oxidative stress are poorly understood. This review focuses on
      molecular mechanisms of increased oxidative stress in diabetes, the relationship
      of oxidant production to hyperglycemia, and the potential interaction of reactive
      carbonyls and lipids in oxidant generation. Using highly sensitive and specific
      gas chromatography-mass spectrometry, molecular signatures of specific oxidation
      pathways were identified in tissues of diabetic humans and animals. These studies
      support the hypothesis that unique reactive intermediates generated in localized
      microenvironments of vulnerable tissues promote diabetic damage. Therapies
      interrupting these reactive pathways in vascular tissue might help prevent
      cardiovascular disease in this high-risk population.

PMID- 17508918
TI  - Cardiac synchronous and dys-synchronous remodeling in diabetes mellitus.
AB  - Glucose-mediated impairment of homocysteine (Hcy) metabolism and decrease in
      renal clearance contribute to hyperhomocysteinemia (HHcy) in diabetes. The Hcy
      induces oxidative stress, inversely relates to the expression of peroxisome
      proliferators activated receptor (PPAR), and contributes to diabetic
      complications. Extracellular matrix (ECM) functionally links the endothelium to
      the myocyte and is important for cardiac synchronization. However, in diabetes
      and hyperhomocysteinemia, a "disconnection" is caused by activated matrix
      metalloproteinase with subsequent accumulation of oxidized matrix (fibrosis)
      between the endothelium and myocyte (E-M). This contributes to "endothelial
      myocyte uncoupling," attenuation of cardiac synchrony, leading to diastolic heart
      failure (DHF), and cardiac dys-synchronizatrion. The decreased levels of
      thioredoxin and peroxiredoxin and cardiac tissue inhibitor of metalloproteinase
      are in response to antagonizing PPARgamma.

PMID- 17508919
TI  - Is the distribution of tissue pO(2) homogeneous?
AB  - Oxygen transport from blood to the mitochondria is dependent on oxygen gradients.
      The interstitial or extracellular pO(2), measured by the phosphorescence-decay
      method, is indicative of these driving forces and the amount of oxygen available
      to the mitochondria. Diverse protocols for sampling tissue pO(2) show that
      measurements sampling only interstitial pO(2) levels provide a reliable
      measurement of the tissue pO(2) level. Present findings lead to the hypothesis
      that tissue has a fairly uniform interstitial fluid pO(2) level and that local
      inhomogeneity due to the presence arteriolar and venular vessels is smoothed out
      by the steep gradients at the microvascular walls.

PMID- 17508920
TI  - Gating the radical hemoglobin to macrophages: the anti-inflammatory role of
      CD163, a scavenger receptor.
AB  - Efficient extracellular hemoglobin (Hb) clearance is essential to prevent
      oxidative- and nitrosative-mediated toxicity. CD163 belongs to group B of the
      scavenger receptor cysteine-rich (SRCR) protein family found on the surface of
      monocytes and macrophages and is responsible for Hb-haptoglobin (Hp) complex
      uptake. Hb uptake by CD163 was thought to proceed exclusively through an Hp
      dependent pathway. However, Hb can interact directly with CD163 via a low
      affinity binding when Hp is absent. As a result, a two-phase hypothesis of Hb
      clearance by monocytes/macrophages suggests that Hp-Hb binding to CD163 is the
      primary mechanism of plasma Hb clearance, while clearance of Hb by direct binding
      to CD163 is secondary to Hp depletion. The authors have considered the ligand
      specificity of CD163 in human macrophages and in a heterologous gene expression
      model to demonstrate that Hb is effectively endocytosed by CD163 in the absence
      of Hp. Additionally, the authors have considered Hb-based oxygen carriers (HBOCs)
      administration as a unique situation during which direct CD163 uptake may be
      relevant as a mechanism of clearance. However, the nature of chemical
      modifications introduced onto the Hb molecule and/or oxidative changes induced in
      the protein appear to influence the extent of CD163 interaction and cellular
      uptake. Here, an overview and novel insights into the role of CD163 in Hb redox
      inactivation and clearance are provided.

PMID- 17508921
TI  - Mitochondrial and nuclear p53 localization in cardiomyocytes: redox modulation by
      doxorubicin (Adriamycin)?
AB  - Reactive oxygen (ROS) and nitrogen species (RNS) generation have been proposed to
      be an important mechanism of doxorubicin (Adriamycin; ADR)-induced cardiotoxicity
      and cardiomyocyte apoptosis, processes that may be mediated by p53 protein. We
      note that ADR treatment resulted in increased levels of p53 protein in
      cardiomyocyte mitochondria and nuclei. Modulation of the cardiomyocyte redox
      state in genetically engineered mice by modulation of enzymes involved in
      metabolism of ROS/RNS, manganese superoxide dismutase (MnSOD), or inducible
      nitric oxide synthase (iNOS), or a combination of these, regulated levels of
      mitochondrial/nuclear p53 in cardiomyocytes after ADR administration. These
      observations led to the hypothesis that mitochondrial/nuclear p53 localization
      and function in the cardiomyocyte response to ADR may be regulated through redox
      dependent mechanism(s).

PMID- 17508923
TI  - Protein-protein interaction inhibitors: small molecules from screening
      techniques.
AB  - Protein-protein interactions play crucial roles in a number of biological
      processes, and, as such, their disruption is becoming an area of intense
      research. Despite the many challenges associated with the development of protein
      protein interaction inhibitors, such as the large and relatively featureless
      interfacial areas involved, there has been considerable success in recent years.
      Importantly, through the existence of protein "hot spots", some of this success
      takes the form of small molecule inhibitors that have been identified from a
      variety of screening techniques.

PMID- 17508924
TI  - Scaffolds for blocking protein-protein interactions.
AB  - Due to the pivotal roles that protein-protein interactions play in a plethora of
      biological processes, the design of therapeutic agents targeting these
      interactions has become an attractive and important area of research. The
      development of such agents is faced with a variety of challenges. Nevertheless,
      considerable progress has been made in the design of proteomimetics capable of
      disrupting protein-protein interactions. Those inhibitors based on molecular
      scaffold designs hold considerable interest because of the ease of variation in
      regard to their displayed functionality. In particular, protein surface mimetics,
      alpha-helical mimetics, beta-sheet/beta-strand mimetics, as well as beta-turn
      mimetics have successfully modulated protein-protein interactions involved in
      such diseases as cancer and HIV. In this review, current progress in the
      development of molecular scaffolds designed for the disruption of protein-protein
      interactions will be discussed with an emphasis on those active against
      biological targets.

PMID- 17508925
TI  - Towards drugs targeting multiple proteins in a systems biology approach.
AB  - Protein-protein interactions are increasingly becoming drug targets. This is
      understandable, since they are crucial at all levels of cellular expression and
      growth. In practice, targeting specific disease-related interactions has proven
      difficult, with success varying with specific complexes. Here, we take a Systems
      Biology approach to targeting protein-protein interactions. Below, we first
      briefly review drug discovery targeted at protein-protein interactions; we
      classify protein-protein complexes with respect to their types of interactions
      and their roles in cellular function and as being targets in drug design; we
      describe the properties of the interfaces as related to drug design, focusing on
      hot spots and surface cavities; and finally, in particular, we cast the
      interactions into the cellular network system, highlighting the challenge of
      partially targeting multiple interactions in the networks as compared to hitting
      a specific protein-protein interaction target. The challenge we now face is how
      to pick the targets and how to improve the efficiency of designed partially
      specific multi-target drugs that would block parallel pathways in the network.

PMID- 17508926
TI  - Small molecule protein-protein inhibitors for the p53-MDM2 interaction.
AB  - This article describes recent progress in the development of small molecule
      protein-protein inhibitors of the p53-MDM2 (purine double minute 2, or HDM2 for
      the human congener) protein-protein interaction, with special attention to the
      diversity of chemotypes reported to disrupt this protein-protein interaction. In
      >50% of all human cancers, the tumor suppressor 53 KDa phospho-protein p53 is
      either mutated or deleted. The discovery that MDM2 (HDM2) negatively regulates
      p53 and therefore inhibits the tumor-suppressor activity of p53 has instigated
      numerous drug discovery campaigns aimed at disrupting this protein-protein
      interaction as a potential cancer therapy. Once regarded as intractable targets
      disrupted by only large macromolecules, protein-protein interactions (PPI) are
      now mainstream targets due in large part to the intensive effort applied to the
      study of p53 and the surprising diversity of small molecules (peptides, natural
      products, terphenyl and other alpha-helix mimetics, chalcones, piperidines,
      piperazines, fused indoles, isoindolinones, spiro-oxindoles, cis-imidazolines
      (nutlins), quinolinol and benzodiazepines) capable of disrupting the p53-HDM2
      PPI. In addition, drug discovery researchers have employed a number of screening
      approaches and technologies to identify SMPPIs of the p53-HDM2 interaction, and
      these discovery paradigms will be discussed. This review will detail the biology
      of the p53-MDM2 interaction, the major classes of SMPPIs and key medicinal
      chemistry and in vitro/in vivo biological data reported through October 2006.

PMID- 17508927
TI  - Small molecule inhibition of the Bcl-X(L)-BH3 protein-protein interaction: proof
      of-concept of an in vivo chemopotentiator ABT-737.
AB  - The Bcl-2 family of anti-apoptotic proteins are key regulators of programmed cell
      death. Bcl-2 and its closely related Bcl-X(L) counterpart are one of several pro
      survival proteins which can share up to four highly conserved domains known as
      the BH1, BH2, BH3 and BH4 domains. These domains form the basis of a well defined
      groove whereupon a heterodimeric protein-protein interaction can occur with pro
      apoptotic BH3 proteins such as Bad, Bid and Bim. Extensive evidence clearly
      indicates a strong correlation between neoplastic progression and deregulation of
      apoptotic pathways. Overexpression of Bcl-X(L) is associated with tumor
      progression, poor prognosis and resistance to chemotherapy. Antagonism of Bcl
      X(L) is therefore viewed as a means to mimic the endogenous apoptotic pathways
      initiated by Bad, Bid and other pro-apoptotic proteins. Several successful
      approaches to block the Bcl-X(L)-BH3 binding groove have been reported but only
      recently have proteomimetics been found which could prove to be clinically useful
      as new anticancer agents capable of overcoming apoptosis resistance. ABT-737 is
      an example of one of the first small-molecule inhibitors of Bcl-2/X(L) proteins
      shown to be efficacious in vivo, causing complete regression in small-cell lung
      carcinoma tumour xenografts in mice. This review will focus on the recent
      advances surrounding the non-peptidic Bcl-2/X(L) inhibitor ABT-737 developed by
      Abbot laboratories and highlight the key structural characteristics found within
      this unique BH3 alpha-helical mimetic.

PMID- 17508928
TI  - Small molecule inhibitors of the XIAP protein-protein interaction.
AB  - The X-linked inhibitor of apoptosis proteins (XIAP) is thought to play a key role
      in the unchecked proliferation of cancer cells by interfering with the signaling
      cascade leading to cell death. The structure and mechanism of XIAP has been
      widely investigated and characterized over the past few years, to the point where
      this may be the best understood apoptosis protein inhibitor. As a result, XIAP is
      viewed as an attractive target for the treatment of cancer. To date, several
      research groups have reported on the discovery of small molecule inhibitors of
      this protein. This review focuses on the discovery and optimization of these
      leads.

PMID- 17508929
TI  - Disruption of the Keap1-containing ubiquitination complex as an antioxidant
      therapy.
AB  - The transcription of antioxidant response element (ARE)-containing cytoprotective
      genes has been proposed as a means to combat oxidative stress-related disorders,
      such as cancer and Parkinson's disease. Transactivation of the ARE requires the
      transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Cellular
      levels of Nrf2 protein are regulated by the Kelch-like ECH-associated protein 1
      (Keap1), a substrate adaptor protein for the ubiquitin ligase machinery and
      subsequent proteasomal degradation. Recently, detailed studies have elucidated
      the structure and interactions of the Keap1-containing ubiquitin ligase complex.
      Here, we propose that small molecule modulation of Keap1 protein:protein
      interactions may permit Nrf2's nuclear accumulation and the transcription of ARE
      dependent genes to enhance cellular resistance to oxidative insult.

PMID- 17508931
TI  - The search for drug leads targeted to the beta-secretase: an example of the roles
      of computer assisted approaches in drug discovery.
AB  - The inhibition of beta-secretase has become a very promising approach to control
      the onset and progression of Alzheimer's disease due to its involvement in the
      generation of amyloid plaques. The main goal of the many drug discovery projects
      targeting this enzyme is the identification of highly specific, non-peptidic
      compounds with low molecular weight, characteristics that are desirable for drug
      leads with low toxicity that have to transverse the blood brain barrier. We
      describe the main approaches used in the discovery of novel inhibitors, including
      substrate specificity, target structure based design, and high throughput
      screening (HTS), both in vitro and in silico. We place special emphasis in the
      receptor based design and in silico HTS, two strategies that make wide use of
      computer assisted tools. To exemplify the usefulness and versatility of computer
      tools in this endeavor we use the computer generated 'enzyme's binding site cast'
      to rationalize qualitatively some salient structural features of known beta
      secretase second generation inhibitors, and for guiding the review of many of the
      ligands whose complexes with the enzyme have been studied by X-ray
      crystallography. We discuss the use made by other authors of molecular modelling
      for the understanding of the very special characteristics of ligand binding to
      beta-secretase and for the design of new inhibitors. Finally, we review the quest
      for non-peptidic inhibitors that has led to the use of HTS in vitro and in
      silico. The screening of extensive libraries resulted in a few low affinity
      compounds that do not fit into the key S1/S1' pockets, indicating that this is
      not an easy target to block.

PMID- 17508932
TI  - Structural models of class a G protein-coupled receptors as a tool for drug
      design: insights on transmembrane bundle plasticity.
AB  - G protein-coupled receptors (GPCRs) interact with an extraordinary diversity of
      ligands by means of their extracellular domains and/or the extracellular part of
      the transmembrane (TM) segments. Each receptor subfamily has developed specific
      sequence motifs to adjust the structural characteristics of its cognate ligands
      to a common set of conformational rearrangements of the TM segments near the G
      protein binding domains during the activation process. Thus, GPCRs have fulfilled
      this adaptation during their evolution by customizing a preserved 7TM scaffold
      through conformational plasticity. We use this term to describe the structural
      differences near the binding site crevices among different receptor subfamilies,
      responsible for the selective recognition of diverse ligands among different
      receptor subfamilies. By comparing the sequence of rhodopsin at specific key
      regions of the TM bundle with the sequences of other GPCRs we have found that the
      extracellular region of TMs 2 and 3 provides a remarkable example of
      conformational plasticity within Class A GPCRs. Thus, rhodopsin-based molecular
      models need to include the plasticity of the binding sites among GPCR families,
      since the "quality" of these homology models is intimately linked with the
      success in the processes of rational drug-design or virtual screening of chemical
      databases.

PMID- 17508933
TI  - Trp/Met/Phe hot spots in protein-protein interactions: potential targets in drug
      design.
AB  - Protein-protein interactions are crucial to biological functions. Consequently,
      designing drugs to control protein-protein interactions is receiving increasing
      attention. Protein structures can associate in different ways. Analysis of the
      structures of protein-protein complexes using amino acid sequence order
      independent multiple structural comparison algorithms, led us to conclude that
      the amino acids Trp, Met, and Phe are important for protein-protein interactions.
      Hence, in principle, drug design targeting the Trp/Met/Phe should modulate
      protein functions effectively. Several clusters of the Trp/Met/Phe residues are
      involved in the p53 protein-protein interactions. The best example in this regard
      is the Phe19/Trp23 of p53, which binds to transcriptional factors and to the MDM2
      protein. In the HIV related proteins, the Trp/Met/Phe residues have roles in the
      dimerization of the transcriptase (p51/p66) and in cell-fusion processes,
      including the gp120-CD4 interaction and the gp41 six-helix bundle formation.
      Trp/Met/Phe residues are preferred in 'normal' functional protein-protein
      interactions and they also appear to be exploited in amyloid formation,
      especially the phenylalanine. Comparison of binding propensity and amyloid
      formation preference reveals that apart from Lysine, Isoleucine is the least
      structurally conserved in protein binding sites and has a high propensity in
      sequences forming amyloids. Thus, this may suggest that nature tends to avoid Ile
      conservation in protein-protein interaction to avoid amyloid formation. In this
      regards, Trp/Met/Phe as well as Ile may be targeted to modulate protein-protein
      interaction.

PMID- 17508934
TI  - Ligand docking and structure-based virtual screening in drug discovery.
AB  - Ligand-docking-based methods are starting to play a critical role in lead
      discovery and optimization, thus resulting in new 'drug-candidates'. They offer
      the possibility to go beyond the pool of existing active compounds, and thus find
      novel chemotypes. A brief tutorial on ligand docking and structure-based virtual
      screening is presented highlighting current problems and limitations, together
      with the most recent methodological and algorithmic developments in the field.
      Recent successful applications of docking-based tools for hit discovery, lead
      optimization and target-biased library design are also presented. Special
      consideration is devoted to ongoing efforts to account for protein flexibility in
      structure-based virtual screening.

PMID- 17508935
TI  - Medicinal chemistry and bioinformatics--current trends in drugs discovery with
      networks topological indices.
AB  - The numerical encoding of chemical structure with Topological Indices (TIs) is
      currently growing in importance in Medicinal Chemistry and Bioinformatics. This
      approach allows the rapid collection, annotation, retrieval, comparison and
      mining of chemical structures within large databases. TIs can subsequently be
      used to seek quantitative structure-activity relationships (QSAR), which are
      models connecting chemical structure with biological activity. In the early
      1990's, there was an explosion in the introduction and definition of new TIs. The
      Handbook of Molecular Descriptors by Todeschini and Consonni lists more than 1500
      of these indices. At the end of the last century, researchers produced a large
      number of TIs with essentially the same advantages and/or disadvantages.
      Consequently, many researchers abandoned the definition of TIs for a time. In our
      opinion, one of the problems associated with TIs is that researchers aimed their
      efforts only at the codification of chemical connectivity for small-sized drugs.
      As a consequence, recently it seems that we have arrived at "Fukuyama's End of
      History in TIs definition". In the work described here, we review and comment on
      the "quo vadis" and challenges in the definition of TIs as we enter the new
      century. Emphasis is placed on new chiral TIs (CTIs), flexible TIs for unifying
      QSAR models with multiple targets, topographic indices (TPGIs), TIs for DNA and
      protein sequences, TIs for 2D RNA structures, TPGIs and drug-protein or drug-RNA
      quantitative structure-binding relationship (QSBR) studies, TIs to encode protein
      surface information and TIs for protein interaction networks (PINs).

PMID- 17508936
TI  - Structure based drug design for HIV protease: from molecular modeling to
      cheminformatics.
AB  - Significant progress over the past decade in virtual representations of molecules
      and their physicochemical properties has produced new drugs from virtual
      screening of the structures of single protein molecules by conventional modeling
      methods. The development of clinical antiviral drugs from structural data for HIV
      protease has been a major success in structure based drug design. Techniques for
      virtual screening involve the ranking of the affinity of potential ligands for
      the target site on a protein. Two main alternatives have been developed: modeling
      of the target protein with a series of related ligand molecules, and docking
      molecules from a database to the target protein site. The computational speed and
      prediction accuracy will depend on the representation of the molecular structure
      and chemistry, the search or simulation algorithm, and the scoring function to
      rank the ligands. Moreover, the general challenges in modern computational drug
      design arise from the profusion of data, including whole genomes of DNA, protein
      structures, chemical libraries, affinity and pharmacological data. Therefore,
      software tools are being developed to manage and integrate diverse data, and
      extract and visualize meaningful relationships. Current areas of research include
      the development of searchable chemical databases, which requires new algorithms
      to represent molecules and search for structurally or chemically similar
      molecules, and the incorporation of machine learning techniques for data mining
      to improve the accuracy of predictions. Examples will be presented for the
      virtual screening of drugs that target HIV protease.

PMID- 17508937
TI  - Small-scale immunopurification of cytochrome c oxidase for a high-throughput
      multiplexing analysis of enzyme activity and amount.
AB  - COX (cytochrome c oxidase) deficiency is one of the main causes of genetic
      mitochondrial disease and presents with multiple phenotypes, depending on whether
      the causative mutation exists in a mitochondrial or nuclear gene and on whether
      it involves an altered catalytic or structural component or an assembly factor
      for this membrane-embedded 13-subunit enzyme complex. COX deficiency is routinely
      observed in AD (Alzheimer's disease), although there is continuing debate about
      whether this is a causative or a secondary consequence of the condition. Altered
      levels of COX and reduced oxidative phosphorylation capacity have been reported
      in other common diseases, including cancer, and are seen as unwanted side effects
      in a number of drug treatments, particularly with antiretroviral and antibiotic
      treatments. Here, we introduce a simple, rapid, high-throughput 96-well plate
      protocol that uses a multiplex approach to determine the amount and activity of
      COX, which should find widespread use in evaluating the above diseases and in
      drug safety studies. Importantly, the method uses very small amounts of cell
      material or tissue and does not require the isolation of mitochondria. We show
      the utility of this approach by example of the analysis of fibroblasts from
      patients with COX activity deficiency and the effect of the antiretroviral drug
      ddC (2',3'-dideoxycytidine) on the biogenesis of the enzyme.

PMID- 17508939
TI  - Practice development - part 2: evaluating a practice initiative.

PMID- 17508940
TI  - Patients' perceptions of transrectal prostate biopsy: a qualitative study.
AB  - This study explored men's experiences of transrectal prostate biopsy. Fifty men
      who had had a prostate biopsy talked about the experience as part of an in-depth
      interview; 36 were interviewed in 2000 about all aspects of prostate cancer, and
      14 in 2005 about their experience of prostate-specific antigen testing,
      subsequent investigations and treatment. Men were recruited via urologists,
      general practitioners and support groups. In both studies, we aimed to include
      men of various ages, from different backgrounds, who lived, and had been
      investigated and treated, in different parts of the UK. A qualitative
      interpretive approach was taken, combining thematic analysis with constant
      comparison. Most men described the procedure as merely 'uncomfortable', but some
      found it stressful, exhausting and extremely painful. Worries included the fear
      that cancer cells might pass from a man to his wife during ejaculation, and that
      a biopsy might spread cancer cells to other parts of the body. Men should be
      given detailed information before a biopsy, so that they are well aware of what
      might happen. They should also be given the opportunity to voice their fears, so
      that they can be reassured, and offered some form of pain relief.

PMID- 17508941
TI  - Differences in prevalence rates of psychological distress and mental disorders in
      inpatients and outpatients with breast and gynaecological cancer.
AB  - Research has demonstrated that in a significant number of patients, mental
      disorders occur with cancer. However, it is not known whether there is a
      difference for comorbidity in patients who are treated in hospitals versus
      outpatient care. The present study initially screened patients for psychological
      distress and quality of life with breast and gynaecological cancer. Instruments
      used were the General Health Questionnaire-12 and the Hospital Anxiety and
      Depression Scale, and for quality of life, the SF-36 Health Survey was used. In
      the next stage, a subsample of patients was assessed with standardized clinical
      interview (Composite International Diagnostic Interview) for the detection of
      mental disorders according to the Diagnostic and Statistical Manual of Mental
      Disorders, 4(th) Edn. The frequency of psychologically distressed patients in
      inpatient care is about 10% higher than in outpatient care. A higher risk (OR =
      1.2-2.0) for mental disorders is found for inpatients compared with outpatients
      in all prevalence periods. Although differences in psychological distress,
      quality of life and prevalences of mental disorders failed to achieve statistical
      significance, the descriptive results indicate that inpatients with breast or
      gynaecological cancer suffer more often from psychological distress and comorbid
      mental disorders than outpatients. Outpatient treatment can therefore be
      considered as an important alternative to inpatient care, as patients with
      comparable disease severity adjust similarly or even better without full hospital
      care.

PMID- 17508942
TI  - Clinical and electrophysiological features of peripheral neuropathy induced by
      administration of cisplatin plus paclitaxel-based chemotherapy.
AB  - The current prospective study sought to trace the incidence and severity of
      cisplatin plus paclitaxel (DDP+P)-induced neuropathy and to determine its
      clinical and electrophysiological pattern. Furthermore, it was attempted to
      describe its evolution by following up the course of peripheral neuropathy (PN)
      during chemotherapy as well as 3 months after its discontinuation. Thirteen adult
      patients scheduled to be treated with six courses of cumulative DDP+P-based
      regimens for a non-myeloid malignancy participated in this study. These patients
      were clinically and electrophysiologically monitored at baseline, during
      chemotherapy and 3 months after its discontinuation. The severity of PN was
      summarized by means of a modified PN score. Evidence of PN was disclosed in nine
      of the 13 patients (69.2%). The mean PN score for patients that manifested some
      grade of PN was 17.3 +/- 6.1 (range 9-28). All longitudinal comparisons
      concerning the motor conduction velocities (MCV) variables failed to reach
      significance. By contrast, comparisons of the mean changes at baseline and each
      of the follow-up studies revealed a significant decrease in all sensory action
      potentials examined. The follow-up evaluation performed 3 months after the
      discontinuation of chemotherapy showed that the DDP+P-induced neuropathy persists
      and progresses over time. Our results indicate that the majority of patients
      treated with a DDP+P-based regimen at full dose intensities would manifest an
      axonal, predominately sensory PN, of mild to moderate severity, which would
      persist for several months after the discontinuation of chemotherapy.

PMID- 17508943
TI  - Prosthetic rehabilitation of persons with lower limb amputations due to tumour.
AB  - The retrospective study was to analyse some characteristics of patients with
      lower limb amputations due to tumour, as well as the prosthetic rehabilitation.
      From 2000 to 2004, we observed 46 patients (25 men and 21 women) who were
      admitted prosthetic rehabilitation after a lower limb amputation due to tumours.
      We examined their medical documentation and recorded their general clinical
      status paying a special attention to the local status of the stump. The average
      age of patients was 51 +/- 17.11 years. Osteosarcoma was the most frequent cause
      in 26%. The trans-femoral amputation was in 50% and the knee disarticulation was
      in 8.7%. The average duration of prosthetic rehabilitation was 35 +/- 7.94 days.
      The average daily use of the prosthesis was 5.5 h. At the time of admission for
      rehabilitation, 10.9% of patients were using wheelchairs, 8.7% were using walkers
      and 80.4% were using two crutches to assist their walking abilities, whereas at
      the time of discharge 89.1% of patients used two crutches and 4.4% used one
      crutch for assistance, while 6.5% were able to walk unassisted. The adequate
      prosthetic rehabilitation in patients with lower limb amputations due to tumour
      is important preconditions for reintegration into the family and community.

PMID- 17508944
TI  - Beck Depression Inventory: exploring its psychometric properties in a palliative
      care population of advanced cancer patients.
AB  - To validate the Greek version of the Beck Depression Inventory (BDI)-21 items in
      advanced cancer patents attending a palliative care unit. The scale was
      translated with the forward-backward procedure into Greek. It was administered
      twice, with a 1-week interval, to 105 patients with advanced cancer. The patients
      also completed the Hospital Anxiety and Depression (HAD) scale, while researchers
      recorded data on demographic characteristics, disease status and treatment
      regimen. The Greek version of the BDI had overall Cronbach's alpha 0.906. The
      most significant correlations were found between BDI and performance status (P <
      0.0005), gender (P = 0.031) and family status (P = 0.009). The test-retest
      reliability in terms of Spearman-rho, Pearson-rho coefficient and Kendall's tau-b
      was also satisfactory (P < 0.0005). Validity as performed using known-group
      analysis showed good results. The Inventory discriminated well between subgroups
      of patients differing in disease severity as defined by the Eastern Cooperative
      Oncology Group performance status. Correlations between the BDI and the HAD scale
      was 0.544 for the anxiety subscale and 0.657 for the depression subscale.
      Multiple regression analysis was conducted and predicted that the contribution of
      gender, family status and performance status to BDI is high. These psychometric
      properties of the Greek version of the BDI confirm it as a valid and reliable
      measure when administered to patients with advanced cancer.

PMID- 17508945
TI  - The European Organization for Research and Treatment of Cancer core quality of
      life questionnaire (QLQ-C30 version 3.0 Turkish) in cancer patients receiving
      palliative radiotherapy.
AB  - The aim of this study was to evaluate the efficacy of palliative radiotherapy in
      patients with advanced cancer in terms of improvement in the quality of life
      [quality of life questionnaire (QLQ)], and to assess the correlation between the
      Eastern Cooperative Oncology Group (ECOG) performance status and the European
      Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (Turkish
      version 3.0). A total of 88 patients with advanced malignant disease treated with
      palliative radiotherapy were included in the study. All patients completed the
      EORTC QLQ-C30 questionnaire before and after treatment, and the patient
      performance status during the pre-treatment and post-treatment phase (ECOG <or=
      2, >2) was correlated to the EORTC QLQ C-30 with subscales. Most patients (87.5%)
      had metastatic disease, and the remaining (12.5%) had locally advanced disease.
      Comparing the patients in terms of performance status, those with a better
      performance status (<or=2) reported a statistically significant higher level on
      the functioning scales and lower levels on all the symptom scales on both the pre
      treatment and post-treatment assessments. Cronbach's alphas were calculated to
      estimate the internal consistency and reliability for both pre- and post
      treatment functioning and symptom scales. The results of this study contribute to
      our understanding of the impact of comprehensive palliative radiotherapy, and to
      its assessment.

PMID- 17508946
TI  - Antiangiogenic metronomic chemotherapy and hyperthermia in the palliation of
      advanced cancer.
AB  - Among a large series of cancer patients treated with a combination of
      chemotherapy and sessions of hyperthermia, particular attention was given to a
      specific group of patients with advanced cancer who refused standard, aggressive,
      treatment. In these cases, hyperthermia was associated to low-dose (metronomic)
      chemotherapy. No toxicity was reported in any of our patients, while a marginal
      benefit in terms of tumour progression was observed. During therapy, we could
      detect a coagulative perturbation that deserves careful discussion. In our
      opinion, this experience should be matter of debate to conclude if current
      response criteria (WHO/UICC and RECIST) in treating cancer patients are really
      suitable tools to evaluate new, and non-aggressive anticancer strategies.

PMID- 17508947
TI  - Association of epidermal growth factor receptor mutations in lung cancer with
      chemosensitivity to gefitinib in isolated cancer cells from Japanese patients.
AB  - Somatic mutations in the tyrosine kinase domain of the epidermal growth factor
      receptor (EGFR) gene are reported to be associated with clinical responsiveness
      of lung cancer to gefitinib, an EGFR tyrosine kinase inhibitor. To elucidate the
      association between somatic mutations and the pharmacological actions of
      gefitinib, the chemosensitivity of isolated cancer cells from the lungs of
      Japanese patients to gefitinib was examined by the collagen gel-droplet embedded
      culture drug sensitivity test in vitro. In 30 specimens isolated from non-small
      cell lung cancer patients, mutations were observed in eight tumour specimens
      (27%) and chemosensitivity to gefitinib was observed in seven specimens (23%).
      However, somatic mutations were not predominantly associated with
      chemosensitivity to gefitinib in vitro. Both mutation and chemosensitivity
      frequencies in this study were higher than those reported in studies from the
      United States, indicating a possible ethnic difference. Moreover, both
      frequencies were much higher in females than in males. Since a gender difference
      in chemosensitivity to gefitinib was observed in isolated cancer cells in vitro,
      this suggests that gefitinib works in part through the suppression of EGFR
      signalling, but that other factors, including sex-related factors, may
      participate in gefitinib action.

PMID- 17508948
TI  - Quality of life in lung cancer patients: impact of baseline clinical profile and
      respiratory status.
AB  - As cure is attainable in very few cases of lung cancer, the imperative issue is
      to make quality of life (QOL) as good as possible as part of the palliative care
      package. The aim of this paper was to evaluate the baseline QOL of lung cancer
      patients and observe its association with various clinical parameters and overall
      respiratory status. A total of 101 patients were administered the European
      Organization for Research and Treatment of Cancer core quality of life (EORTC QLQ
      C30, version 3) questionnaire. Clinical profile and measures of respiratory
      status, including spirometry, measures of dyspnoea, and 6-min walk test, were
      recorded. Higher Karnofsky Performance Status (KPS) significantly correlated with
      better global health status (P < 0.001) and healthy level of functioning (P <
      0.001). The cumulative symptom burden was significantly associated with global
      QOL (P = 0.01) and physical, role and cognitive function scales (P < 0.05). All
      dyspnoea measures negatively correlated with global QOL and functioning scales.
      Spirometric indices showed a positive correlation with all functional scales (P <
      0.05) except social. In conclusion, lung cancer patients have unsatisfactory QOL,
      with the global health status and physical functions being most affected. Number
      of symptoms, KPS, dyspnoea and spirometry significantly affect QOL.

PMID- 17508949
TI  - Information needs following a diagnosis of oesophageal cancer; self-perceived
      information needs of patients and family members compared with the perceptions of
      healthcare professionals: a pilot study.
AB  - This pilot study was undertaken to describe patients' and family members'
      information needs following a diagnosis of oesophageal cancer and healthcare
      professionals' (HCP) perceptions concerning patients' and family members'
      information needs. Another aim was to describe patients' and family members'
      satisfaction with information provided. Data were collected by means of a self
      report questionnaire. A total of 15 patients, 16 family members and 34 HCP
      participated. Patients and family members consider most information to be
      important. The high rating for information about tests/treatment and self-care
      means that both patients and family members consider this to be the most
      important areas of information. Healthcare professionals tend to underestimate
      both patients' and family members' needs for information. Patients and family
      members were only partly satisfied with the information received, with patients
      in general more satisfied with information given compared with family members.
      Patients' and family members' needs for information following a diagnosis of
      oesophageal cancer are substantial and have not been adequately met by HCP. A
      qualitative study might be helpful to complete the description of patients' and
      family members' needs. If a questionnaire is employed, it ought to be less
      extensive.

PMID- 17508950
TI  - Usefulness of oral corticosteroid in Rosai-Dorfman disease.
AB  - Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive
      lymphadenopathy, is a benign self-limiting disorder of unknown aetiology, which
      is frequently mistaken for lymphoma. There is no consensus as to the proper
      management of this disorder. In the past, potentially harmful treatments, such as
      antineoplastic drugs, have been advocated. We describe a 25-year-old woman with
      RDD who has had a remarkably favourable response to oral prednisolone therapy.
      Our observation strengthens the conclusions of previous case reports as to the
      effectiveness of corticosteroids in this condition. This article is aimed at
      creating awareness among clinical oncologists about this pseudolymphomatous
      disorder and emphasizing the therapeutic role of corticosteroids.

PMID- 17508951
TI  - Sublingual use of olanzapine in combination with alprazolam to treat agitation in
      a terminally ill patient receiving parenteral nutrition.
AB  - This paper reports the case of a 64-year-old man who was receiving parenteral
      nutrition after repeated operations due to stomach cancer. Olanzapine (orally
      disintegrating tablets) in combination with alprazolam was used successfully to
      relieve this terminally ill patient's anxiety and tension improving his
      relationship with his physicians and his daily life.

PMID- 17508952
TI  - Subsidized complementary therapies for staff and volunteers at a regional cancer
      centre: a formative study.
AB  - In the United Kingdom, the Government has acknowledged workplace stress and
      burnout in the National Health Service by establishing Improving Working Lives
      Standards, which recognize the need for a range of support mechanisms. Staff in
      oncology hospitals experience considerable stress because of the emotional
      intensity of work that involves limited clinical success, sustained contact with
      seriously ill/dying people, and serial bereavement. Evidence suggests that
      providing complementary therapies at work can help to reduce anxiety, depression
      and blood pressure and, thus, increase well-being. We used a purpose-designed
      questionnaire to assess awareness of, access to and the value placed on a
      complementary therapy service for staff and volunteers at a regional cancer
      centre. Free-text data from 167 completed questionnaires, subjected to
      qualitative analysis, revealed an overwhelmingly positive view of the service,
      but concerns about access. The service appeared to be a victim of its own success
      in that it could not meet demand within its existing resources and, thus, meet
      its potential for improving working lives; limits to resources also affected the
      conduct and rigour of our evaluation. We conclude by discussing the impact of the
      evidence-based practice culture on levels of funding for complementary therapy
      services operating in hospital settings.

PMID- 17508953
TI  - Mature cystic renal teratoma in a 25-year-old woman with ipsilateral
      hydronephrosis, urinary tract infection and spontaneous abortion.
AB  - Benign cystic renal teratomas are uncommon clinical entities in our environment.
      To the best of our knowledge, it has never been reported here. Renal teratomas
      are rare and most have been dismissed as retroperitoneal teratomas secondarily
      invading the kidney. We report a case in which benign cystic renal teratoma was
      associated with ipsilateral hydronephrosis, urinary tract infection and
      spontaneous abortion, with histological confirmation in a 25-year-old woman.

PMID- 17508954
TI  - Metaplastic breast carcinoma in a 32-year-old woman in Benin City, Nigeria: a
      rare finding.

PMID- 17508957
TI  - Refill adherence to repeat prescriptions of cancer drugs to ambulatory patients.

PMID- 17508959
TI  - Asthma and methacrylates--gluing together the evidence.

PMID- 17508960
TI  - The ethics of bronchoscopic research in children.

PMID- 17508961
TI  - The role of innate immunity in asthma: leads and lessons from mouse models.
AB  - According to the Hygiene Hypothesis, respiratory infections should protect
      individuals from allergic diseases including asthma, but epidemiologic data on
      the role of infections or exposure to microbial compounds in asthma are
      contradictory. Meanwhile, a number of murine models of airway sensitization are
      available facilitating the elucidation of pathways involved in asthma
      pathogenesis. Such studies have linked antigen presentation by activated
      pulmonary dendritic cells (DCs) with airway sensitization. Toll-like receptors
      (TLRs), which play a major role in innate immunity by sensing various microbial
      compounds, are expressed on DCs, as well as on mast cells (MCs). Activation of
      TLRs by administration of specific bacterial ligands, in particular
      lipopolysaccharide, can augment airway sensitization in mice, and there is
      evidence that this process involves TLR-dependent activation of DCs.
      Intriguingly, viral infection has been shown to increase airway inflammation in a
      murine asthma model via activation of DCs as well. TLR-4-dependent stimulation of
      MCs may also play a role in allergic sensitization in mice, and in vitro studies
      in murine cells show that ligation of TLRs expressed on MCs enhances
      degranulation. Therefore, evidence obtained from studies on mice indicates that
      innate immune responses may promote, rather than protect from, the development as
      well as the exacerbation of asthma.

PMID- 17508962
TI  - Mild asthma: an expert review on epidemiology, clinical characteristics and
      treatment recommendations.
AB  - This review is the synthesis of a working group on mild asthma. Mild asthma
      includes intermittent and persistent mild asthma according to the Global
      Initiative for Asthma (GINA) classification, and affects between 50% and 75% of
      asthmatic patients. Mild asthma is more frequent, more symptomatic, and less well
      controlled in children than in adults. Cohort studies from childhood to adulthood
      show that asthma severity usually remains stable over time. Nevertheless, mild
      asthma can lead to severe exacerbations, with a frequency ranging from 0.12 to
      0.77 per patient-year. Severe exacerbations in mild asthma represent 30-40% of
      asthma exacerbations requiring emergency consultation. In mild asthma,
      inflammation and structural remodelling are constant, of varying intensity, but
      nonspecific. Therapy with inhaled corticosteroids (ICS) decreases bronchial
      inflammation, but has only a slight effect on structural remodelling, and, when
      stopped, inflammation immediately recurs. Permanent low-dose ICS therapy is the
      reference treatment for persistent mild asthma. Effectiveness is to be reassessed
      at 3 months, and if it is insufficient the patient is no longer considered mildly
      asthmatic, and treatment has to be stepped up. As mild asthma is the most
      frequent form of the disease, diagnosis and management require physicians'
      particular attention.

PMID- 17508963
TI  - Asthma treatment: 'magic bullets which seek their own targets'.
AB  - The most fascinating options of the new asthma treatments are probably
      represented by monoclonal antibodies. In fact, these molecules are virtually able
      to interact with whatever specific antigen. Anyway, it is mandatory to understand
      the limits of this group of molecules, in terms of both efficacy and safety. In
      this review, we have analyzed different ways of interfering along the course of
      the cascade of the allergic reaction, targeting different molecules (CD4, TNF
      alpha, IL-4, IL-5, IL-10, IL-12, endothelial adhesion molecules, IgE), showing
      the efficacy and the risks of each kind of treatment. In the end, we focused our
      attention on omalizumab, the monoclonal antibody targeting IgE. Although with
      some restrictions, represented by the high costs and the limitation of its use
      only to a specific subset of patients affected by allergic asthma, at present
      anti-IgE appear to be the only 'magic bullet' for the treatment of allergic
      asthma. In fact, it proved to reduce exacerbations and symptom scores, and to
      improve quality of life, with a very good safety profile.

PMID- 17508964
TI  - Assessment of asthma control and its impact on optimal treatment strategy.
AB  - Achieving and maintaining optimal asthma control is a major asthma management
      goal advocated by the Global Initiative for Asthma (GINA). Recent evidence
      suggests that while asthma control is clearly achievable in most asthmatics, not
      all asthmatics attain optimal asthma control. The difficulty is compounded
      further because patients, physicians and regulatory bodies have different
      perceptions of what is meant by asthma control. The challenge therefore remains
      as to how best to assess asthma control and define management strategies to
      ensure that this control is achieved and maintained. Despite the availability of
      several patient-based tools for assessing asthma control, these are mostly
      employed in a research setting or in selected specialist clinics. A symptom-based
      treatment approach also may have its limitations because patients can be poor
      judges of disease symptoms and severity and under-estimation may lead to
      inadequate treatment of airway inflammation and airway hyperresponsiveness (AHR)
      when treatment is administered as on-demand reliever therapy, since the effect of
      treatment on these underlying features occurs over a longer time course. The
      clinical benefits of sustained maintenance treatment for at least 3 months has
      been documented in recent studies of salmeterol/fluticasone propionate
      combination, which have demonstrated correlations between reduction in airway
      inflammation/AHR and reduction in exacerbation rates. In view of the putative
      limitations of a purely symptom-based asthma management plan, we suggest that
      treatment should be focussed on management of all aspects of the disease rather
      than management of symptoms alone, with a practical approach being treatment for
      a minimum of 3 months with an optimal dose to ensure maximal effects are seen on
      asthma control, airway inflammation, lung function, and remodelling.

PMID- 17508965
TI  - PGE suppresses excessive anti-IgE induced cysteinyl leucotrienes production in
      mast cells of patients with aspirin exacerbated respiratory disease.
AB  - BACKGROUND: Aspirin causes bronchospasm in patients with aspirin exacerbated
      respiratory disease (AERD). The contribution of mast cells to the increased
      cysteinyl-leucotrienes (cys-LTs) detected in AERD patients is however not
      defined. AIMS OF THE STUDY: Effects of prostaglandin (PG) E(2) and inhibitors of
      cyclooxygenase (COX) and lipoxygenase (LO) pathways on mediator release from
      cultured mast cells of normal subjects, aspirin tolerant asthma (ATA) and AERD
      patients were compared to better define the role of mast cells in AERD. METHODS:
      Mast cells were cultured from peripheral blood progenitors and were activated by
      anti-IgE. Histamine, PGD(2) and cys-LTs released were then determined. RESULTS:
      Basal release of all three mediators was similar in all subjects. Although the
      release of all three mediators was increased by anti-IgE, mast cells from AERD
      patients produced significantly more cys-LTs (6.9 +/- 2.0 ng/10(6) cells) than
      normal and ATA subjects (2.3 +/- 0.8 and 1.7 +/- 0.5 ng/10(6) cells,
      respectively). While COX and LO pathway inhibitors did not affect anti-IgE
      induced histamine release, they significantly suppressed the production of PGD(2)
      and cys-LTs, respectively, in all patients. PGE(2) significantly enhanced anti
      IgE induced histamine and PGD(2) release from mast cells of normal subjects but
      not those of ATA and AERD patients. In contrast, PGE(2) suppressed only anti-IgE
      induced cys-LTs release from mast cells of AERD patients. CONCLUSION: We
      speculate that overproduction of cys-LTs is unique to mast cells of AERD patients
      and is particularly sensitive to suppression by PGE(2). Consequently reduction of
      PGE(2) production by aspirin removes this endogenous control of cys-LTs
      overproduction, resulting in asthma attack.

PMID- 17508966
TI  - Alternative splicing of cyclooxygenase-1 gene: altered expression in leucocytes
      from patients with bronchial asthma and association with aspirin-induced 15-HETE
      release.
AB  - BACKGROUND: Cyclooxygenase-1 (COX-1) is a key enzyme involved in generation of
      prostanoids, important mediators and modulators of asthmatic inflammation. In a
      subpopulation of aspirin-sensitive asthmatics (ASA) inhibition of COX-1 by
      nonsteroidal anti-inflammatory drugs results in activation of inflammatory cells
      and development of symptoms. Alternatively spliced variants of COX-1 lacking 111
      bp from exon 9 were described previously but have never been identified in human
      leucocytes peripheral blood leucocytes (PBL) or upper airway epithelial cells. We
      aimed to assess the expression of spliced variants of COX-1 mRNA in PBLs from
      patients with asthma and in healthy subjects (HS) referring the expression to
      patients characteristics (including ASA-sensitivity) and to aspirin-triggered 15
      hydroxyeicosatetraenoic acid (15-HETE) generation. METHODS: The study included 30
      patients with ASA, 30 patients with aspirin-tolerant asthma (ATA) and 30 HS
      serving as controls. Nasal polyps for epithelial cell cultures were obtained from
      10 patients with chronic rhinosinusitis. Expression of full length and spliced
      variants of COX-1 enzyme was detected by RT-PCR and presented as the ratio of
      full-length COX-1 to alternatively spliced COX-1 mRNA [COX-1 alternative splicing
      index (COX-1 AS index)]. Release of eicosanoids (PGE(2) and 15-HETE) by PBLs was
      measured with enzyme immunoassay. RESULTS: In both PBLs and airway epithelial
      cells the expression of full-length product prevailed over spliced variants of
      COX-1 enzyme. Cyclooxygenase-1 AS index was significantly lower in asthmatics as
      compared to HS (1.96 +/- 0.71 vs 2.41 +/- 0.99, P < 0.05) indicating the
      relatively higher expression of the alternative transcript in asthmatic patients.
      Cyclooxygenase-1 AS index was not different between ASA and ATA groups (mean 1.90
      +/- 0.66 vs 2.02 +/- 0.76, respectively, P = 0.39). There was no significant
      association between COX-1 AS index and mean daily dose of inhaled
      glucocorticosteroids or pulmonary function tests (FEV(1), FVC) but in ASA group a
      weak correlation with daily dose of oral glucocorticosteroids was found (r =
      0.39; P = 0.03). In ASA patients there was a significant positive correlation
      between the COX-1 AS index and the percentage of aspirin-triggered increase in 15
      HETE generation (r = 0.51; P < 0.03). CONCLUSIONS: Alternatively spliced variants
      of COX-1 mRNA are differently expressed in patients with bronchial asthma and may
      be associated with aspirin-triggered 15-HETE generation.

PMID- 17508967
TI  - Basement membrane thickening and clinical features of children with asthma.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease, characterized by airway
      inflammation, bronchial hyper-responsiveness, and airway obstruction. Although
      asthma induces partially reversible airway obstruction, obstruction can sometimes
      become irreversible. This may be a consequence of airway remodeling, which
      includes a number of structural changes, such as epithelial detachment, basement
      membrane (BM) thickening, smooth muscle hypertrophy, and new vessel formation.
      This study evaluated children with asthma for the presence of BM thickening.
      METHODS: Eighteen children with asthma and 24 control subjects underwent flexible
      bronchoscopy with endobronchial biopsy. Light microscopy was used to measure BM
      thickness in paraffin-embedded biopsy sections. The association between BM
      thickening and age, sex, duration of asthma, asthma severity, FEV(1), FEV(1)/FVC,
      FEF(25-75%), methacholine PC(20), eosinophil count, and presence of atopy was
      examined. RESULTS: Basement membrane thickness was greater in subjects with
      asthma (8.3 +/- 1.4 microM) than in control subjects (6.8 +/- 1.3 microM, P =
      0.0008). Multiple regression analysis revealed that sex, FEV(1)/FVC, total IgE,
      and atopy (IgE for Dermatophagoides pteronyssinus >0.34 kUA/l) were significant
      predictive factors for BM thickness. There was no significant association between
      BM thickness and age, duration of asthma, FEV(1), FEF(25-75%), methacholine
      PC(20), eosinophil count, or asthma severity. CONCLUSIONS: Basement membrane
      thickening has been known to be present in children with asthma. In addition, we
      report an association between BM thickness and sex, FEV(1)/FVC, total IgE, and
      the presence of IgE specific to D. pteronyssinus.

PMID- 17508968
TI  - Associations of glutathione S-transferase P1, M1, and environmental tobacco smoke
      with wheezing illness in school children.
AB  - BACKGROUND: Polymorphisms at the glutathione S-transferase (GST) were associated
      with asthma-related phenotypes. We hypothesized that the GSTP1 and GSTM1
      genotypes could modify the effects of household environmental tobacco smoke (ETS)
      on childhood wheezing illness. METHODS: We conducted a case-control study
      comprised of 216 lifetime wheezing children and 185 nonwheezing controls, all of
      whom were selected from 2524 fourth- to ninth-grade school children in southern
      Taiwan. RESULTS: Homozygous GSTP1 Ile-105 was significantly associated with
      current wheezing (OR = 1.78, 95% CI 1.04-3.12), but insignificantly associated
      with ever wheezing (OR = 1.26, 95% CI 0.82-1.94). The risks of ever or current
      wheezing on GSTM1 null genotype were positive but not statistically significant.
      Although household ETS exposure was not associated with wheezing illness, after
      excluding subjects having in utero ETS or active smoking habits, the adverse
      effects of household ETS exposure differed significantly by GSTP1-105 genotypes.
      In children without any ETS exposure at home, GSTP1 Ile-105 homozygosity was
      significantly related to increased risks for both ever wheezing (OR = 2.29, 95%
      CI 1.17-4.49) and current wheezing (OR = 4.86, 95% CI 1.86-12.70). In children
      with household ETS exposure, the risks of wheezing illness did not increase for
      those carrying two GSTP1 Ile-105 alleles. Children carrying any GSTP1 Val-105
      allele were at a significantly greater risk of both ever and current wheezing
      when exposed to ETS, with a clear dose-response relationship to the number of
      smokers at home. CONCLUSION: Household ETS exposure is a modifiable cause of
      wheezing illness in a genetically susceptible subpopulation.

PMID- 17508969
TI  - Respiratory effects of exposure to methacrylates among dental assistants.
AB  - BACKGROUND: Case reports of occupational asthma in dental personnel have been
      published, but there is little data on the risk of respiratory disorders related
      to occupational exposure to methacrylates in dental assistants. The objective of
      this study was to investigate the relation of exposure to methacrylates to
      occurrence of respiratory symptoms and diseases among dental assistants. METHODS:
      A cross-sectional study of female dental assistants from the membership register
      of the Finnish Association of Dental Hygienists and Assistants was conducted in
      the Helsinki metropolitan area. A CATI was carried out to collect information on
      health and exposures. A total of 799 dental assistants participated (response
      rate 87%). RESULTS: Daily use of methacrylates was related to a significantly
      increased risk of adult-onset asthma (adjusted OR 2.65, 95% CI 1.14-7.24), nasal
      symptoms (1.37, 1.02-1.84), and work-related cough or phlegm (1.69, 1.08-2.71).
      Nasal symptoms showed a dose-response relation with increasing years of exposure
      to methacrylates, and those with >10 years of exposure had also increased risk of
      hoarseness, dyspnoea, and wheezing with dyspnoea. Dental assistants with a
      history of atopic diseases were particularly susceptible to exposure to
      methacrylates, the adjusted OR for adult asthma being in this group 4.18 (95% CI
      1.02-28.55) and for nasal symptoms 2.11 (1.08-4.19). CONCLUSIONS: This study
      provides new evidence that the risk of adult-onset asthma, nasal symptoms and
      other respiratory symptoms increase significantly with daily use of methacrylates
      in dental assistants' work. The results suggest that exposure to methacrylates
      poses an important occupational hazard for dental assistants.

PMID- 17508970
TI  - Association of control and risk of severe asthma-related events in severe or
      difficult-to-treat asthma patients.
AB  - BACKGROUND: Clinical tools for predicting poor outcomes in asthma patients are
      lacking. This study investigated the association of asthma control and subsequent
      severe asthma-related healthcare events in The Epidemiology and Natural History
      of Asthma: Outcomes and Treatment Regimens (TENOR) study. METHODS: The extent of
      asthma control problems was determined from baseline values of the Asthma Therapy
      Assessment Questionnaire (ATAQ). Patients self-reported the presence of severe
      asthma-related events at 6- and 12-month follow up. Poisson regression models
      determined the adjusted association between baseline control and the likelihood
      of severe asthma-related events. RESULTS: At baseline, 2942 patients (mean age,
      49.6 years; female, 71.9%) had an ATAQ score (no control problems, 17.0%; 1
      control problem, 20.0%; 2 control problems, 30.8%; 3 or 4 control problems,
      32.2%) and at least one severe asthma-related event. After adjustment, subjects
      with three or four control problems were at greater risk for unscheduled office
      visits [relative risk (RR) = 2.8; 95% confidence interval (CI): 2.4-3.2], course
      of oral steroids (RR = 2.9; 95% CI: 2.5-3.3), emergency room visits (RR = 4.1;
      95% CI: 2.7-6.2) or hospitalization (RR = 13.6; 95% CI: 7.4-24.9), vs no control
      problems. Progressively poorer levels of asthma control are associated with
      increasing risk of severe asthma-related events. CONCLUSIONS: This study provides
      evidence of an association between poor asthma control and future severe asthma
      related healthcare events. A validated questionnaire may help clinicians identify
      patients requiring intervention to prevent future severe asthma-related events.

PMID- 17508971
TI  - Differential anti-inflammatory effects of large and small particle size inhaled
      corticosteroids in asthma.
AB  - BACKGROUND: Extra-fine particle formulations of hydrofluoroalkane-134a
      beclometasone dipropionate (HFA-BDP) exhibit clinical effects comparable with
      conventional particle formulations of chlorofluorocarbon beclometasone
      dipropionate (CFC-BDP) at half the dose. There is little data comparing their
      effects on inflammation. We have evaluated the effects of HFA-BDP and CFC-BDP on
      pulmonary and systemic markers of asthmatic inflammation. METHODS: A double-blind
      randomized crossover trial was undertaken comparing the anti-inflammatory effects
      of HFA-BDP (100 and 400 microg/day) and CFC-BDP (200 and 800 microg/day).
      Treatment with montelukast was evaluated as add-on to the higher dose of BDP.
      RESULTS: Compared with baseline after withdrawal of usual asthma therapy, 100
      microg of HFA-BDP significantly attenuated serum eosinophilic cationic protein
      levels (0.61-fold change, 95% CI 0.49-0.77; a 39% reduction, P < 0.001), but 200
      microg of CFC-BDP did not (0.87-fold change, 95% CI 0.63-1.23; P = 1). A dose of
      800 microg of CFC-BDP and 400 microg of HFA-BDP led to reductions in exhaled
      nitric oxide (0.57-fold change, 95% CI 0.44-0.73; a 43% reduction, P < 0.001 and
      0.65-fold change, 95% CI 0.47-0.91; a 35% reduction, P = 0.008, respectively);
      and peripheral eosinophils (-74 cells/microl, 95% CI -146 to -2; P = 0.020 and 
      77 cells/microl, 95% CI -140 to -14; P = 0.012, respectively). Montelukast
      further reduced exhaled nitric oxide (0.81-fold change, 95% CI 0.66-0.98; P =
      0.028) with 400 microg HFA-BDP and eosinophils (-44 cells/microl, 95% CI -80 to 
      8; P = 0.012) with 800 microg CFC-BDP, but not vice versa. CONCLUSION:
      Chlorofluorocarbon beclometasone dipropionate and HFA-BDP have differential
      effects on pulmonary and systemic inflammation, which dictate the additive
      effects of montelukast.

PMID- 17508972
TI  - Unmet needs in asthma: Global Asthma Physician and Patient (GAPP) Survey: global
      adult findings.
AB  - BACKGROUND: The Global Asthma Physician and Patient (GAPP) Survey is the first
      global quantitative survey designed to uncover asthma attitudes and treatment
      practices among separate groups of physicians and patients, with the goal of
      identifying barriers to optimal management. METHOD: A total of 5582 physician and
      patient interviews were conducted globally online, by telephone and face-to-face.
      This paper highlights key global findings from the adult arm (3559 interviews)
      conducted in 16 countries. RESULTS: Physician and patient responses were found to
      differ when respondents were asked the same set of questions. Perceptions of time
      spent on asthma education, the quality of physician-patient communications,
      awareness and experience of side effects and understanding and knowledge of
      treatment noncompliance were found to differ between these two sets of
      respondents. CONCLUSIONS: The GAPP Survey not only defines an unmet need in
      asthma treatment, but also reveals that there is a direct relationship between
      the quality of physician-patient communication, the level of treatment side
      effects and the extent of patient compliance. These survey findings highlight a
      clear need for improved patient-focused care in asthma.

PMID- 17508973
TI  - Novel cytokine peptide-based vaccines: an interleukin-4 vaccine suppresses airway
      allergic responses in mice.
AB  - BACKGROUND: Monoclonal antibodies or soluble receptors have been used to block
      over-produced endogenous cytokines. However, they have disadvantages of short
      half-lives, high costs, and possible adverse effects. Using interleukin (IL)-4 as
      a model target, we sought to develop a novel therapeutic strategy by constructing
      an IL-4 peptide-based vaccine for blocking IL-4 on a persistent basis, and to
      evaluate its efficacy in a mouse model of asthma. METHODS: A peptide was selected
      by antigenic prediction and structure analysis of IL-4/receptor complex. The
      vaccine was constructed by employing truncated hepatitis B core antigen as
      carrier with the peptide inserted using gene engineering methods. It was then
      expressed, purified and identified. Prior to intraperitoneal sensitization and
      intranasal challenge with ovalbumin, mice were subcutaneously immunized three
      times with the vaccine, or the carrier or saline as controls. Serum antibodies,
      inflammatory cells in bronchoalveolar lavage fluids (BALF), lung histology, and
      responsiveness to inhaled methacholine were analyzed. RESULTS: The vaccine
      presented as virus-like particles and reacted to polyclonal anti-IL-4 in Western
      blotting. Vaccinated mice produced high titers of IgG to IL-4. Serum ovalbumin
      specific IgE, eosinophil accumulation in BALF, goblet cell hyperplasia, tissue
      inflammation and methacoline-induced respiratory responses were markedly
      suppressed in vaccinated mice with statistical significance, as compared with
      those in the control groups. CONCLUSIONS: Administration of this novel IL-4
      vaccine led to an overall decrease in the development of airway allergic
      inflammatory responses. The results indicate that cytokine peptide-based vaccines
      hold potential for treatment of asthma and, by extension, other diseases where
      over-expressed cytokines play a pivotal role in pathogenesis.

PMID- 17508974
TI  - Nonspecific provocation of target organs in allergic diseases: EAACI-GA(2)LEN
      consensus report.
AB  - It is widely accepted that nonspecific tissue reactivity is a distinct
      pathophysiological hallmark of allergic diseases, influenced by genetic and
      environmental factors different from those involved in causing sensitization and
      allergen response of target organs. This consensus document aims at reviewing
      procedures currently used for nonspecific provocation of the bronchi, nose and
      eye and for measuring their responsiveness to nonspecific stimuli.

PMID- 17508975
TI  - Toward a 'united' management of 'united airways disease': the role of
      otorhinolaryngologists and pneumologists.

PMID- 17508976
TI  - Recurrent egg allergy in adulthood.

PMID- 17508977
TI  - Usefulness of serum interleukin-10 in determining food tolerance.

PMID- 17508978
TI  - A visit to the mother in law--a hidden cause for urticaria.

PMID- 17508979
TI  - Multiple fixed drug eruption due to intradermal test with metamizole.

PMID- 17508980
TI  - Type I allergic reaction to benzimidazole antihelmintics.

PMID- 17508981
TI  - Atopy, wheeze and bronchial responsiveness in young Chilean adults. Do dietary
      antioxidants matter?

PMID- 17508983
TI  - Retrospective analysis of artemisinin pharmacokinetics: application of a
      semiphysiological autoinduction model.
AB  - AIMS: To describe the time-course of the autoinduction of artemisinin by applying
      a semi-physiological pharmacokinetic model. METHODS: Plasma concentration-time
      data from six clinical studies involving oral administration of artemisinin to
      healthy subjects and malaria patients were included in the analysis. NONMEM was
      used to apply a semi-physiological model incorporating metabolizing enzymes and a
      pharmacokinetic model including a separate hepatic compartment. RESULTS: The
      model described the data well. The hepatic extraction ratio increased from 0.74
      at pre-induced conditions to 0.98 after autoinduction of metabolism. CONCLUSIONS:
      Our model successfully described the time-course of autoinduction of metabolism
      of artemisinin in subjects receiving oral artemisinin.

PMID- 17508985
TI  - New developments in the pharmacotherapy of cocaine abuse.
AB  - Despite huge advances in the neuroscience of substance abuse and dependence in
      the past 20 years, no approved pharmacological treatment exists for cocaine
      abuse. The available drugs for the treatment of cocaine abuse are poorly
      effective, hence the need for new compounds to be screened and tested for
      efficacy: targeting symptoms might improve the effectiveness of the treatment of
      cocaine abuse and dependence. On the basis of the known neurochemistry of
      cocaine, some target compounds have been studied: among others, BP-897, a D3
      partial agonist; vanoxerine, a highly selective inhibitor of dopamine uptake;
      aripiprazole, a partial mixed-action agonist approved for the treatment of
      schizophrenia. Recently modafinil, approved for the treatment of narcolepsy,
      proved effective in favouring cocaine abstinence in cocaine-abusing people. Some
      placebo-controlled studies also reported the effectiveness of topiramate, a
      licensed antiepileptic drug, and of tiagabine, a gamma-aminobutyric acid (GABA)
      re-uptake inhibitor also approved as an anticonvulsant; both compounds increased
      cocaine abstinence with no serious adverse events. Promising results came from
      two more compounds acting on the GABA circuits, baclofen and valproic acid.
      Finally disulfiram, prescribed with active psychosocial therapy, was found to
      favour higher retention rates and longer abstinence periods from both alcohol and
      cocaine in polydrug-abusing patients. An alternative approach rests on the use of
      vaccines, to date in the experimental stage still. Psychosocial treatments are a
      useful companion in the pharmacotherapy of cocaine abuse, with group therapy and
      contingency management therapies improving motivation and social functioning,
      particularly in patients abusing alcohol as well.

PMID- 17508986
TI  - Morphine withdrawal decreases responding reinforced by sucrose self
      administration in progressive ratio.
AB  - Previous studies have shown that withdrawal from psychostimulant drugs such as d
      amphetamine or methamphetamine decreases motivation to work for a natural
      reinforcement, which is thought to be associated with the withdrawal-induced
      depressive state and hypofunction of the mesolimbic dopamine system. However, to
      our knowledge, studies exploring the effect of morphine withdrawal on motivation
      for a natural reinforcement are lacking. The purpose of the present study was to
      examine whether motivation to work for a natural reinforcement changes during
      morphine withdrawal. Three groups of male Sprague-Dawley rats were trained to
      respond on a nose poke for a 4% sucrose solution under a progressive ratio
      schedule and were subsequently administered a 10-day regimen of injection of high
      or low dose of morphine or saline. Their duration of break point and withdrawal
      symptoms were assessed. The finding showed that break points were significantly
      reduced on day 1 and persisted to at least day 10 of withdrawal without change in
      locomotor activity. There were hardly any differences bear mentioning when
      comparing the magnitude of the decrease between the high- and the low-dose group,
      whereas the withdrawal scales were significant greater in the high-dose group
      than in the low-dose group. The results suggest that the morphine withdrawal
      resulted in decreased motivation to obtain the natural reinforcement. The
      progressive ratio procedure may be a useful technique for evaluation of changes
      in motivation for natural reinforcing stimuli following withdrawal from opiates.

PMID- 17508987
TI  - Effect of cannabinoids on platelet serotonin uptake.
AB  - Serotonin is involved in many of the same processes affected by cannabinoids;
      therefore, we investigated in vitro and in vivo effects of these drugs on the
      function of serotonin transporter. The effect of Delta(9)-tetrahydrocannabinol
      (Delta(9)-THC), endocannabinoid anandamide and synthetic cannabinoid receptor
      agonist WIN 55,212-2 on platelet serotonin uptake and membrane microviscosity was
      examined in 19 marijuana smokers and 20 controls. (1) Serotonin uptake was
      inhibited at higher doses of Delta(9)-THC (IC(50) = 139 micromol/l), anandamide
      (IC(50) = 201 micromol/l) or WIN 55,212-2 (IC(50) = 17.4 micromol/l); the
      inhibition was found non-competitive. Delta(9)-THC, anandamide and WIN 55,212-2
      produced different effects on the membrane microviscosity. (2) Maximal velocity
      of platelet serotonin uptake was significantly increased in a group of chronic
      marijuana smokers suffering impairment of cognitive functions when compared with
      controls. Opposite effect of marijuana smoking on the serotonin uptake efficiency
      was observed in males beside females. In summary, this study provides evidence
      that (1) Activity of serotonin transporter is acutely affected by cannabinoids at
      relatively high drug concentrations; this effect is indirect and can be partially
      accounted for the changes in the membrane microviscosity. (2) Increase of maximal
      velocity of the serotonin uptake could be understood as adaptation change in the
      serotonergic system induced by chronic cannabis use. A hypothesis was supported
      that lowered serotonin uptake may reflect a gender-related differences in effects
      of psychoactive cannabinoids.

PMID- 17508988
TI  - Changes in central dopaminergic systems and morphine reward by prenatal and
      neonatal exposure to bisphenol-A in mice: evidence for the importance of exposure
      period.
AB  - Bisphenol-A has been extensively evaluated for toxicity in a variety of tests as
      the most common environmental endocrine disruptors. In a previous study, we
      reported that exposure to bisphenol-A affects the development of the central
      dopaminergic system in the mouse limbic area. The present study was undertaken to
      investigate the relationship between the developmental toxicity of bisphenol-A
      and its exposure period. The exposure to bisphenol-A during either organogenesis
      or lactation, but not implantation and parturition, significantly enhanced the
      morphine-induced hyperlocomotion and rewarding effects. Furthermore, exposure to
      bisphenol-A during either organogenesis or lactation also produced an up
      regulation of dopamine receptor function to activate G-protein in the mouse
      limbic forebrain. These results indicate that both organogenesis and lactation
      are more sensitive to the bisphenol-A-induced developmental neuronal toxicology
      than any other periods. In conclusion, the present data suggest that the
      organogenesis and lactation are the most important period to cause the
      alternation of dopaminergic system by bisphenol-A exposure in the mouse.

PMID- 17508989
TI  - Perinatal alcohol exposure enhances nocistatin levels in adulthood.
AB  - In earlier experiments perinatal hormonal imprinting by alcohol decreased the
      hormone content of immune cells for life. In the present study, both a single day
      (15% on the third postnatal day) and a long-term treatment schedule of alcohol
      exposure (3% for 21 days) of dams during lactation significantly (P < 0.01)
      enhanced endogenous levels of nocistatin in the blood plasma as well as in the
      cerebrospinal fluid of the offspring, measured in 3-month-old rats. Our data
      suggest that alcohol consumption during lactation can cause a life-long influence
      on nocistatin levels in the offspring and most likely modify nocistatin-related
      functions such as pain tolerance.

PMID- 17508990
TI  - Does naltrexone affect craving in abstinent opioid-dependent patients?
AB  - Naltrexone blocks the opioid receptors that modulate the release of dopamine in
      the brain reward system and therefore blocks the rewarding effects of heroin and
      alcohol. It is generally assumed that naltrexone leads to reduction of craving,
      but few studies have been performed to prove this. The purpose of the present
      study was to examine the effect of the administration of naltrexone on craving
      level after rapid opioid detoxification induced by naltrexone. A naturalistic
      study was carried out in which patients were followed during 10 months after
      rapid detoxification. Data about abstinence, relapse, and naltrexone use were
      collected by means of urine specimens. Craving was measured by the visual
      analogue scale craving, the Obsessive Compulsive Drug Use Scale, and the Desires
      for Drug Questionnaire. Results showed that patients who relapsed in opioid use
      experienced obviously more craving than abstinent people. Patients who took
      naltrexone did not experience significant less craving than those who did not.
      These results suggest that the use of opioids is associated with increased
      craving and that abstinence for opioids is associated with less craving,
      independent of the use of naltrexone. This is in contrast to the general opinion.
      Because of the naturalistic design of the study, no firm conclusions can be
      drawn, but the results grounded the needs of an experimental study.

PMID- 17508991
TI  - The influence of blood alcohol concentrations of around 0.03% on
      neuropsychological functions--a double-blind, placebo-controlled investigation.
AB  - There is a general agreement that blood alcohol concentrations (BACs) of about
      0.05% result in impairment of the ability to drive. This fact has been supported
      by means of experiments. In addition, there are only a few studies to date
      investigating low BACs. The present study aims to investigate the extent and
      quality of cognitive changes in low BACs of around 0.03%. Sixteen healthy male
      subjects were examined in a double-blind, placebo-controlled study. During the
      trials the BAC was regulated to about 0.03%. As part of the study a record was
      made of the general level of intelligence, subjective impairments, possible
      depressive symptoms, general ability to perform, vigilance, divided attention,
      response times and performance of memory. Statistical analysis took place using
      the two-period crossover design. Verbal intelligence, general performance,
      vigilance (optical stimuli), divided attention, vigilance towards acoustic
      stimuli and the general response time to acoustic and visual-acoustic sequential
      stimuli, and memory were not impaired significantly by a BAC of around 0.03%. The
      total response and motor response time to optical stimuli as well as decision
      time about sequential optical stimuli were, however, significantly changed for
      BACs of around 0.03%. In conclusion, the present results show that already in
      BACs of around 0.03%, particular cognitive functions which rely on perception and
      processing of visual information, are significantly impaired. This was evident in
      the more complex and urgent tasks.

PMID- 17508992
TI  - Physical health problems among patients seeking treatment for alcohol use
      disorders: a study in six European cities.
AB  - The present study investigates physical health problems among patients with
      alcohol use disorders at alcohol treatment agencies in six European cities. The
      sample comprised 315 patients with a primary alcohol use disorder. Data were
      collected at admission to treatment using a structured research protocol, and
      ratings were made by a medically qualified physician subsequent to a physical
      examination of the patient. Physical health problems were extremely common: 79%
      of the sample had at least one problem, and 59% had two or more problems. Health
      problems were often serious, and 60% had at least one health problem that
      required treatment. The most common problems were gastrointestinal and liver
      disorders, but about a quarter of the sample had cardiovascular or neurological
      problems. Frequency of drinking, duration of alcohol use disorder, and severity
      of alcohol dependence were associated with increased physical morbidity. Current
      smoking status and age were also associated with poorer physical health. Older
      drinkers had more physical health problems although they were less severely
      alcohol dependent than their younger counterparts. The high prevalence of
      physical health problems among problem drinkers provides opportunities of
      screening for alcohol use disorders not only in specialist alcohol treatment
      services but also in other health-care settings. It is recommended that alcohol
      treatment agencies should provide a full routine health screen of patients at
      admission to treatment with provision or referral to appropriate treatment.

PMID- 17508993
TI  - Elevated urinary aluminium in current and past users of illicit heroin.
AB  - The use of illicit heroin is associated with aberrant neurology of unknown
      aetiology and various psychiatric illnesses. Aluminium, which is a proven
      neurotoxin, is present in significant amounts in illicit heroin and may also be
      volatilized and inhaled following the vaporization of heroin off aluminium foil
      ('Chasing the Dragon'). The purpose of this study was to establish if the use of
      illicit heroin was associated with an increase in the body burden of aluminium.
      We have used graphite furnace atomic absorption spectrometry to measure the
      aluminium and iron contents of the urine of current and past users of illicit
      heroin and used these data to estimate body burdens of aluminium. Urinary
      excretion of aluminium is the most effective non-invasive indicator of the body
      burden of aluminium and was found to be significantly (P < 0.001) higher in users
      of illicit heroin, range 14-3382 nmol/mmol creatinine (mean +/- SD; 222 +/- 491
      nmol/mmol creatinine), than in a normal non-drug abusing control population,
      range 23-74 nmol/mmol creatinine (mean +/- SD; 43 +/- 19 nmol/mmol creatinine).
      Exposure to aluminium from the use of illicit heroin may be of particular
      significance because the urinary excretion of iron, another major contaminant of
      illicit heroin, in users (mean +/- SD; 53 +/- 63 nmol/mmol creatinine) was not
      significantly different (P > 0.05) from the control population (mean +/- SD; 38
      +/- 18 nmol/mmol creatinine). We have shown for the first time that the use of
      illicit heroin may be a significant contributor to the body burden of aluminium.
      Further research will be required to determine if adventitious aluminium has a
      role in heroin use-related neuropathology and neurology.

PMID- 17508995
TI  - Polymorphisms of the dopamine D4 receptor gene (DRD4 VNTR) and cannabinoid CB1
      receptor gene (CNR1) are not strongly related to cue-reactivity after alcohol
      exposure.
AB  - Polymorphisms in the D4 dopamine receptor gene (DRD4) and the CB1 cannabinoid
      receptor gene (CNR1) have been associated with a differential response to alcohol
      after consumption. The goal of the present study was to investigate whether heavy
      drinkers with these polymorphisms would respond with enhanced cue-reactivity
      after alcohol exposure. Eighty-eight male heavy drinkers were genotyped for the
      DRD4 variable number of tandem repeats (VNTR) [either DRD4 long (L) or short (S)]
      and the CNR1 rs2023239 polymorphism (either CT/CC or TT). Participants were
      exposed to water and beer in 3-minute trials. Dependent variables of main
      interest were subjective craving for alcohol, subjective arousal and salivary
      reactivity. Overall, no strong evidence was found for stronger cue-reactivity (=
      outcome difference between beer and water trial) in the DRD4 L and CNR1 C allele
      groups. The DRD4 VNTR polymorphism tended to moderate salivary reactivity such
      that DRD4 L participants showed a larger beverage effect than the DRD4 S
      participants. Unexpectedly, the DRD4 L participants reported, on average, less
      craving for alcohol and more subjective arousal during cue exposure, compared
      with the DRD4 S participants. As weekly alcohol consumption increased, the CNR1 C
      allele group tended to report more craving for alcohol during the alcohol
      exposure than the T allele group. The DRD4 and CNR1 polymorphisms do not appear
      to strongly moderate cue-reactivity after alcohol cue exposure, in male heavy
      drinkers.

PMID- 17508994
TI  - The human protein kinase C gamma gene (PRKCG) as a susceptibility locus for
      behavioral disinhibition.
AB  - This study explores the association between a highly heritable behavioral
      disinhibition phenotype and the protein kinase C gamma (PRKCG) gene in an
      ethnically diverse youth sample from Colorado, USA. The rationale for this study
      was based on the impulsive behavior and increased ethanol consumption observed in
      the protein kinase C gamma (PKC-gamma)-deficient mouse model. Two composite
      behavioral disinhibition phenotypes and their component behavioral scores
      [conduct disorder, attention-deficit hyperactivity disorder (ADHD), substance
      experimentation (SUB) and novelty-seeking] were examined for association with
      five independent PRKCG single nucleotide polymorphisms (SNPs). Association
      analysis for the five individual SNPs revealed modest genetic association of Exon
      14 (rs2242244) and Upstream (rs307941) markers with the behavioral disinhibition
      composite variables in the combined, Hispanic and African-American samples.
      Additionally, haplotype-based association analysis for two SNPs located in Intron
      3 (rs402691) and Exon 6 (rs3745406) indicated a significant overall association
      of the PRKCG locus with the ADHD-hyperactive subscale scores in the combined and
      Caucasian samples, supporting the relation between impulsive behaviors and the
      PRKCG gene. A significant haplotype association was also observed with SUB scores
      but only in the Hispanic ethnic group, highlighting the marker variability for
      each ethnic group. In conclusion, our results support the role of the PKC-gamma
      enzyme in behavioral impulsivity previously observed in mice. This study provides
      the first exploration of the PRKCG gene and its association with behavioral
      disinhibition and warrants further study in other larger population samples.

PMID- 17508996
TI  - Association between dopamine transporter genotypes and smoking cessation: a meta
      analysis.
AB  - This review assessed the evidence of an association between genotypes of the
      dopamine transporter (DAT1, SLC6A3) 3' untranslated region (3'UTR) variable
      number of tandem repeats (VNTR) and smoking cessation. Five studies (seven
      cohorts) comprising 2155 subjects were included in the meta-analysis. All gave
      data on the number of smokers who had stopped smoking and the number still
      smoking for those with one or more variant 9-repeat alleles and other genotypes.
      Three studies (comprising five cohorts) were cross-sectional population surveys
      and two were smoking cessation treatment programs with follow-up. Four of the
      five studies (six of the seven cohorts) showed a trend in favor of cessation when
      the variant 9-repeat allele was present, although only one study showed a
      statistically significant effect. The pooled odds ratio in favor of a greater
      likelihood of cessation for the variant 9-repeat allele was 1.15 [95% confidence
      interval (CI) = 0.97-1.37]. In a more refined analysis where cohorts within
      studies were treated as separate samples and adjusted odds ratios were used, the
      overall pooled odds ratio in favor of cessation with the 9-repeat alleles was
      1.20 (95% CI = 1.01-1.43). These results support the hypothesis that the DAT1
      3'UTR VNTR polymorphism is associated with smoking cessation. One or more variant
      9-repeat alleles relative to the more common 10-repeat allele confers a greater
      likelihood of cessation, indicative of lower dependence on tobacco. The effect
      was a 20% increase in the odds of cessation for those with a variant allele.

PMID- 17508997
TI  - Epilepsy and recreational scuba diving: an absolute contraindication or can there
      be exceptions? A call for discussion.
AB  - Recreational scuba diving is a popular sport, and people with epilepsy often ask
      physicians whether they may engage in diving. Scuba diving is not, however,
      without risk for anyone; apart from the risk of drowning, the main physiological
      problems, caused by exposure to gases at depth, are decompression illness, oxygen
      toxicity, and nitrogen narcosis. In the United Kingdom, the Sport Diving Medical
      Committee advises that, to dive, someone with epilepsy must be seizure free and
      off medication for at least 5 years. The reasons for this are largely
      theoretical. We review the available evidence in the medical literature and
      diving websites. The risk of seizures recurring decreases with increasing time in
      remission, but the risk is never completely abolished. We suggest that people
      with epilepsy who wish to engage in diving, and the physicians who certify
      fitness to dive, should be provided with all the available evidence. Those who
      have been entirely seizure-free on stable antiepileptic drug therapy for at least
      4 years, who are not taking sedative antiepileptic drugs and who are able to
      understand the risks, should then be able to consider diving to shallow depths,
      provided both they and their diving buddy have fully understood the risks.

PMID- 17508998
TI  - An anthropological study about epilepsy in native tribes from Central and South
      America.
AB  - PURPOSE: Epilepsy was a well-recognized disease in pre-Columbian cultures.
      However, anthropological studies about epilepsy in native cultures living at the
      present time are scarce. The objective of this paper was to study native
      perception and myths about epilepsy, their magic-religious healing rites and
      ceremonies, and the natural treatments that archaic cultures used. METHODS: An
      anthropological fieldwork was performed in Central and South America with Tzeltal
      Maya (Chiapas, Mexico, 1995), Kamayura (Matto Grosso, Brazil, 1999) and Uru
      Chipaya people (Bolivian Andes, 2004). We collected information from shamans and
      medicine men about epilepsy beliefs and the use of traditional treatments.
      RESULTS: Epilepsy is called tub tub ikal by Tzeltal people. It is caused by an
      attack suffered by the animal spirit who accompanies the person, after a fight
      between the spirits who serve the forces of good and evil. People with chronic
      epilepsy are considered witches. Epilepsy is called teawarup by Kamayura, and is
      caused by the revenge of the spirit (mama'e) of the armadillo killed by a
      huntsman. It is treated with two roots, tsimo and wewuru, kneaded and diluted in
      water. Epilepsy is called tukuri by the Chipaya people, and is originated by a
      witchcraft that enters into the nose and the head, as a wind. Tukuri is treated
      with a ritual animal sacrifice called willancha, and by taking several dried
      insect infusions and bird's blood. CONCLUSION: These American native cultures
      have developed a system of orally transmitted knowledge about epilepsy based on
      magic-religious traditions.

PMID- 17508999
TI  - Epilepsy and toxocariasis: a case-control study in Burundi.
AB  - PURPOSE: A case-control study to assess the relationship between epilepsy and
      toxocariasis was carried out in the Kiremba population, Burundi. METHODS: People
      with epilepsy (PWE) were diagnosed according to the definition proposed by the
      International League Against Epilepsy (ILAE). Seizures were classified according
      to the classification proposed by ILAE in 1981. One control per case was selected
      matched by age (+/-5 years). Control subjects also lived in Kiremba, had neither
      neurological disorders nor kinship with the PWE. Cases and controls were assessed
      serologically for antibodies against Toxocara canis by an immunoblotting assay.
      Odds ratios (ORs) and 95% CI were determined using conditional regression
      analysis for matched case-control study. RESULTS: One hundred ninety-one PWE (99
      men and 92 women) and 191 age-matched controls (72 men and 112 women) were
      enrolled in the study. Of the 191 PWE, 113 presented partial seizures while 73
      generalized seizures and five were unclassifiable. Antibodies anti T. canis were
      found in 114 PWE (59.7%) and in 97 controls (50.8%). Multivariate analysis
      (conditional logistic regression) showed a significant association between
      positivity for T canis and epilepsy with an adjusted OR of 2.13 (95% CI 1.18
      3.83; p-value 0.01). CONCLUSIONS: We found a significant association between
      toxocariasis and epilepsy. In agreement with a previous study, our finding
      suggests that toxocariasis may increase the risk of developing epilepsy in
      endemic areas and could participate to the high burden of epilepsy in tropical
      areas.

PMID- 17509000
TI  - Ethnic differences in the incidence of seizure disorders in children from
      Bradford, United kingdom.
AB  - We sought to determine if there are differences in the incidence of seizure
      disorders between the children of the indigenous and immigrant (predominantly
      Pakistani) populations of Bradford, United Kingdom. Annual incidence rates per
      100,000 for new onset seizures were calculated along with Townsend deprivation
      scores. The incidence of seizures (including febrile and single) was 153 (95%CI
      104-139). The rate was significantly higher in south Asians (SA) (220; 184-255)
      compared to non-south Asians (non-SA) (121; 104-139), mainly because of febrile
      seizures whose incidence was 87 (136-169) overall and 142 (114-170) and 61 (49
      74) in SA and non-SA, respectively. There were no significant differences in the
      rates of nonfebrile seizures (non-FebSz) overall and of idiopathic non-FebSz
      between racial groups but the rate for symptomatic/cryptogenic non-FebSz was
      significantly higher in SA (22; 10-34) compared to non-SA (6; 2-10). The
      occurrence of seizure disorders correlated with social deprivation.

PMID- 17509001
TI  - Vagus nerve stimulation therapy induces changes in heart rate of children during
      sleep.
AB  - PURPOSE: This study analyzed changes in the heart rates of children receiving
      vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. METHODS:
      Changes in the heart rates of ten children receiving VNS therapy for
      pharmacoresistant epilepsy were evaluated with polysomnographic recordings,
      including electrocardiogram (ECG), EEG, thoraco-abdominal distension, nasal
      airflow, and VNS artifacts. Measurements during stimulation were compared with
      those at baseline for each patient. RESULT: While the VNS therapy pulse generator
      was delivering stimulation, the heart rates of four children increased
      significantly (p < 0.01), decreased for one child, and increased at the end of
      the stimulation for one child. The heart rates of four children did not change.
      Changes in heart rate varied during VNS, within stimulation cycles for individual
      children and from one child to another. Changes in heart rate differed between
      rapid eye movement (REM) and non-REM (NREM) sleep states. Respiratory changes
      (increases in frequency and decreases in amplitude) were concomitant with the
      changes in heart rate. CONCLUSION: In this case series of children with
      pharmacoresistant epilepsy, cardiorespiratory variations occurred while the VNS
      therapy pulse generator was delivering stimulation. Understanding these
      variations may allow further optimization of VNS parameters.

PMID- 17509002
TI  - Bilateral white matter diffusion changes persist after epilepsy surgery.
AB  - PURPOSE: Bilateral white matter diffusion tensor imaging (DTI) abnormalities have
      been reported in patients with temporal lobe epilepsy (TLE) and unilateral mesial
      temporal sclerosis (MTS), but it is unknown whether these are functional or
      structural changes. We performed a longitudinal study in patients with unilateral
      MTS who were seizure-free for 1 year after surgery to determine whether the
      observed presurgical white matter diffusion abnormalities were reversible.
      METHODS: Eight TLE patients with unilateral MTS who were seizure-free after
      anterior temporal resection and 22 healthy subjects were recruited. DTI was
      performed before surgery and at 1-year follow-up. Tractography and region-of
      interest (ROI) analyses were performed in the fornix, cingulum, genu, and
      splenium of the corpus callosum and external capsules. Diffusion tensor
      parameters were compared between groups and before and after surgery in the
      patient group. RESULTS: The fornix, cingulum, and external capsules showed
      preoperative bilateral abnormal diffusion parameters (i.e., decreased diffusion
      anisotropy and increased mean and perpendicular diffusivities). The fornix and
      cingulum ipsilateral to the resected mesial temporal structures showed signs of
      wallerian degeneration at 1-year follow-up. The contralateral tracts of the
      fornix, cingulum, and external capsules, as well as the genu of the corpus
      callosum, failed to show a normalization of their diffusion parameters.
      CONCLUSIONS: The irreversibility of the white matter DTI abnormalities on seizure
      freedom suggests underlying structural abnormalities (e.g., axonal/myelin
      degradation) as opposed to functional changes (e.g., fluid shifts due to
      seizures) in the white matter.

PMID- 17509003
TI  - Founder effect with variable age at onset in Arab families with Lafora disease
      and EPM2A mutation.
AB  - PURPOSE: We observed three apparently unrelated and geographically separate Arab
      families with Lafora disease in Israel and the Palestinian territories. METHODS:
      We clinically evaluated the families and analyzed their DNA for EPM2A mutations.
      RESULTS: Of seven individuals with Lafora disease, the clinical onset varied from
      13 to 20 years. All three families shared the same novel homozygous deletion in
      EPM2A. Haplotype analysis around the deletion showed that the families shared a
      common homozygous haplotype. The boundaries of this haplotype varied between
      families and even within one family. CONCLUSIONS: We conclude that considerable
      variability in the age at onset of Lafora disease can occur within families.
      Identical mutations can be associated with the classic adolescent presentation,
      as well as late-onset cases. Haplotype analysis suggests that this EPM2A mutation
      arose many generations previously, so it may be of importance for cases
      distributed more widely in the Middle East.

PMID- 17509004
TI  - Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous
      reactions in Han Chinese.
AB  - A previous study conducted in Taiwan found a 100% association between HLA-B*1502
      allele and carbamazepine-induced Stevens-Johnson syndrome (SJS) in Han Chinese
      subjects, with an extremely high odds ratio compared with carbamazepine-tolerant
      subjects (odds ratio = 2,504). We examined this association in 24 Hong Kong Han
      Chinese subjects who had cutaneous adverse reactions induced by different
      antiepileptic drugs (AEDs). They were matched with 48 AED-tolerant controls. HLA
      B*1502 was associated with severe cutaneous reactions (SCR) induced by AEDs,
      which included carbamazepine, phenytoin, and lamotrigine (p = 0.001, odds ratio =
      17.6), but was not associated with maculopapular exanthema (MPE) (p = 0.32).
      Further studies in larger samples of ethnically matched subjects should be
      conducted to confirm the findings. Identification of genetic polymorphisms
      predisposing to development of AED-induced SCR offers the possibility of avoiding
      these high-risk drugs in genetically susceptible individuals.

PMID- 17509005
TI  - Epilepsy in resource poor countries--suggestion of an adjusted classification.

PMID- 17509006
TI  - Hormone replacement therapy in women with epilepsy.

PMID- 17509008
TI  - Psychiatric disorders in juvenile myoclonic epilepsy.

PMID- 17509009
TI  - Parasomnias versus epilepsy: common grounds and a need to change the approach to
      the problem.

PMID- 17509011
TI  - Nonconvulsive status epilepticus versus triphasic encephalopathy.

PMID- 17509012
TI  - A possible role of the thalamus in some cases of sudden unexpected death in
      epilepsy.

PMID- 17509014
TI  - From molecules to motion: altering neuronal ion channel function can lead to
      changes in intestinal motility.

PMID- 17509015
TI  - Appetite and obesity: a gastroenterologist's perspective.
AB  - This review focuses on the gastrointestinal tract's control of appetite and
      interventions directed to the gut that are effective in the treatment of obesity.
      It examines the evidence linking gut hormones to the control of both appetite and
      upper gastrointestinal motility, the evidence that stomach function is altered
      and contributes to satiation in obesity and outlines the principles of therapy
      for obesity which are directed at the gastrointestinal tract. These therapies
      impair fat absorption or alter stomach functions through pharmacological, device,
      endoscopic, or surgical approaches. Gastroenterologists need to understand the
      role of factors controlling appetite in order to effectively manage the
      increasing number of obese patients and the ways the gut function may be altered
      as a result of the treatments and their complications.

PMID- 17509016
TI  - Regional differences in expression of TPH-1, SERT, 5-HT(3) and 5-HT(4) receptors
      in the human stomach and duodenum.
AB  - The aim of this study was to increase the understanding of the role of
      serotonergic signalling in normal gastroduodenal function at a molecular level.
      Mucosal biopsy specimens were collected from the fundus, antrum and duodenum of
      11 healthy subjects. Serotonin (5-HT)-positive cells were counted and the mRNA
      levels of tryptophan hydroxylase (TPH), serotonin transporter (SERT), 5-HT(4)
      receptor and 5-HT(3) receptor subunits were quantified by real-time reverse
      transcription polymerase chain reaction. The number of 5-HT-positive cells was
      larger in the duodenum compared with the stomach (P < 0.001). Serotonin transport
      protein expression was 19-fold higher in the duodenum compared with the antrum
      and 457-fold higher compared with the fundus (P < 0.001). Tryptophan hydroxylase
      1 expression was lower in the duodenum compared with the antrum and fundus
      (regional differences -2.3 and -3.6, respectively). The 5-HT(4) receptor and the
      5-HT(3C) and 5-HT(3E) receptor subunits were more abundantly expressed in
      duodenum compared with the stomach (P < 0.001). The larger number of 5-HT
      positive cells, the higher expression of 5-HT(3) and 5-HT(4) receptors, and in
      particularly the higher uptake capacity of 5-HT in the duodenum, point out to a
      more prominent role of serotonergic signalling at the mucosal level in the
      duodenum compared with the stomach.

PMID- 17509017
TI  - Ultrastructural injury to interstitial cells of Cajal and communication with mast
      cells in Crohn's disease.
AB  - Crohn's disease associated dysmotility has been attributed to fibrosis and damage
      to enteric nerves but injury to interstitial cells of Cajal (ICC) could also be
      involved. We assessed ICC in specimens obtained from patients with Crohn's
      disease and determined the relation between ICC and the inflammatory infiltrate,
      particularly mast cells (MC) using quantitative immunohistochemistry and electron
      microscopy. Ultrastructural injury to ICC was patchy in all ICC subtypes but ICC
      Auerbach's plexus (AP) showed damage more frequently, i.e. swelling of
      mitochondria, decreased electron density, autophagosomes and partial depletion of
      the cytoplasm. Light microscopy confirmed a significant decrease in c-kit
      immunoreactivity for ICC-AP and an increased number of MC in the muscularis
      externa. Electron microscopy showed MC exhibiting piecemeal degranulation and
      making frequent and selective membrane-to-membrane contact with all types of
      injured ICC which suggests chronic release of granule content to affect ICC.
      Extent of ICC injury was not associated with duration of the disease. In
      conclusion, ultrastructural injury and loss of ICC-AP is evident in Crohn's
      disease. Epidemiological and morphological data suggest that ICC have the
      capacity to regenerate in spite of the chronic insult. The muscularis hosts a
      marked number of MC that exhibit piecemeal degranulation associated with ICC and
      may facilitate ICC maintenance.

PMID- 17509018
TI  - Distension-induced gastric accommodation in functional dyspepsia: effect of
      autonomic manipulation.
AB  - Functional dyspepsia (FD) is associated with impaired gastric accommodation and
      autonomic dysregulation. The aim of this study was to investigate the effects of
      autonomic manipulation on distension-induced gastric accommodation in subjects
      with and without FD, using a newly developed gastric barostat paradigm. Twelve
      healthy subjects (HS) and 18 subjects with FD had four barostat examinations
      each: no intervention, intravenous atropine (1 mg), vagal stimulation (mental
      relaxation with deep breathing) and acute stress stimulation (serial subtraction
      task). Intrabag pressure increased from 1 to 15 mmHg in 5 min (ramp phase), and
      was maintained at 15 mmHg for 5 min (tonic phase). Volume responses were analysed
      using predefined parameters. There were no significant group differences in
      accommodation variables between HS and subjects with FD. The FD group could be
      subdivided into two distinct subgroups: subgroup 1 (n = 7, 38%) with low maximum
      volume and accommodation rate, and subgroup 2 with normal accommodation (n = 11).
      In subgroup 1, but not in subgroup 2 atropine increased maximum volume and
      accommodation rate substantially. Neither mental stress nor mental relaxation
      changed any of the accommodation variables. In a subgroup of subjects with FD,
      impairment of distension-induced gastric accommodation can be improved by
      cholinergic blockade, but not by acute physiological autonomic manipulation.

PMID- 17509019
TI  - Autonomic nervous system response to a solid meal and water loading in healthy
      children: its relation to gastric myoelectrical activity.
AB  - The aim of this study was to investigate the correlation of gastric myoelectrical
      and autonomic activities in healthy children. Simultaneous recordings of
      electrogastrography (EGG) and electrocardiogram (ECG) were performed in healthy
      children before and after a solid meal and water loading respectively. The
      autonomic activity was assessed by spectral analysis of the heart rate
      variability (HRV). The solid meal resulted in an increase in EGG-dominant
      frequency (2.92 cpm vs 3.16 cpm, P < 0.05), dominant power (46.9 dB vs 53.7 dB, P
      < 0.05) and percentage normal slow waves (81.9%vs 89.0%, P < 0.05), while only
      dominant power increased following water loading. Power in the low-frequency band
      of HRV (LF) was significantly increased and power in the high-frequency band of
      HRV (HF) significantly decreased following the solid meal. Postprandial LF was
      positively and HF negatively correlated with the postprandial increase in EGG
      dominant power. Water loading was not associated with any significant changes in
      HRV parameters. These results suggest that both vagal and sympathetic pathways
      are involved in modulation of gastric myoelectrical activity.

PMID- 17509020
TI  - Effects of modulators of Ca(2+)-activated, intermediate-conductance potassium
      channels on motility of the rat small intestine, in vivo.
AB  - The movements of the intestine shift between different motor patterns, including
      between propulsion and mixing, but there is little information concerning
      mechanisms that may lead to changes in the patterns of motility. We have
      investigated the influence on intestinal motility of drugs that affect the after
      hyperpolarization potential (AHP) of intrinsic primary afferent neurons (IPANs).
      The current of the AHP is carried by the intermediate conductance, calcium
      activated, potassium (IK) channel. In anaesthetized rats, the IK channel blocker,
      1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (0.05-1 mg kg(-1), i.v.) disrupted
      the regular propulsive pressure waves that occur in the small intestine and
      reduced propulsion of the contents (after 1 mg kg(-1), the fluid propelled was
      <25% of control). If the propulsion in the intestine was regular, the IK channel
      opener, 5,6-dichloro-1-ethyl-2-benzimidazolinone (DC-EBIO, 0.1 mg kg(-1) h(-1))
      had no effect. DC-EBIO (0.1 mg kg(-1) h(-1)) restored propulsive activity after
      the nitric oxide synthase inhibitor, Nomega-nitro-l-arginine had changed motility
      to a mixing pattern. We suggest that the AHP determines the synchrony of action
      potential firing in synaptically coupled IPANs, and that this synchrony
      influences the patterns of firing of muscle motor neurons, and hence the pattern
      of contraction of the muscle and whether the pattern is predominantly propulsive
      or predominantly mixing.

PMID- 17509021
TI  - Stimulation of neuronal receptors, neuropeptides and cytokines during
      experimental oil of mustard colitis.
AB  - Oil of mustard (OM), administered intracolonically, produces severe colitis in
      mice that is maximized within 3 days. The purpose of this study was to
      characterize the cytokine response, and to establish expression patterns of
      enteric neuronal mediators and neuronal receptors affected during active colitis.
      We measured the changes in the mRNA levels for neuronal receptors and mediators
      by real-time PCR, and cytokine and chemokine protein levels in the affected
      tissue. Significant increases in neuronal receptors, such as transient receptor
      potential A1 (TRPA1), cannabinoid type 1 receptor, neurokinin 1 receptor (NK1R)
      and delta-opioid receptor; prokineticin-1 receptor; and soluble mediators, such
      as prodynorphin, proenkephalin1, NK1, prokineticin-1 and secretory leukocyte
      protease inhibitor, occurred. Significant increases in cytokines, such as
      interleukin (IL)-1beta, IL-6 and granulocyte macrophage colony stimulating factor
      (GM-CSF), and in chemokines, such as macrophage chemotactic protein 1 (MCP-1),
      macrophage inflammatory protein 1 (MIP-1alpha) and Kupffer cell derived chemokine
      (KC), were detected, with no changes in T-cell-derived cytokines. Furthermore,
      immunodeficient C57Bl/6 RAG2(-/-) mice exhibited OM colitis of equal severity as
      seen in wt C57Bl/6 and CD-1 mice. The results demonstrate rapidly increased
      levels of mRNA for neuronal receptors and soluble mediators associated with pain
      and inflammation, and increases in cytokines associated with macrophage and
      neutrophil activation and recruitment. Collectively, the data support a
      neurogenic component in OM colitis coupled with a myeloid cell-related, T- and B
      cell-independent inflammatory component.

PMID- 17509022
TI  - Sphincter of Oddi function in the Australian brush-tailed possum is inhibited by
      intragastric ethanol.
AB  - The role of sphincter of Oddi (SO) function in alcoholic acute pancreatitis (AP)
      is unclear. We aimed to compare the effect of i.v. and intragastric (IG) ethanol
      on SO function (i.e. trans-sphincteric flow; TSF) and investigate possible neural
      mechanisms. The involvement of gastric mucosal damage was also investigated by
      pretreatment with pantoprazole. In anaesthetized Australian possums, blood
      pressure (BP), TSF and blood ethanol concentrations were measured after i.v. or
      IG ethanol. Possums were subjected to acute vagotomy, atropine, L-nitro arginine
      methyl ester (L-NAME) or pantoprazole pretreatment prior to IG ethanol. BP was
      not significantly altered by ethanol. Ethanol decreased TSF in a dose and route
      dependent manner. The lowest dose of IG ethanol reduced TSF but this response was
      not duplicated by i.v. ethanol producing the same blood ethanol concentrations.
      Acute vagotomy, atropine or L-NAME pretreatment blocked the ethanol-induced
      decrease in TSF and simultaneously suppressed the blood ethanol concentration.
      Pantoprazole pretreatment reduced the TSF response and blood ethanol
      concentrations implicating mechanisms induced by gastric mucosal damage. We
      conclude that ethanol (and/or its metabolites) reduces TSF via humoral and neural
      mechanisms involving vagal pathways, muscarinic receptors and nitric oxide.
      Reduced TSF could contribute to the onset of AP.

PMID- 17509023
TI  - Dual pulse intestinal electrical stimulation normalizes intestinal dysrhythmia
      and improves symptoms induced by vasopressin in fed state in dogs.
AB  - To assess effects of dual pulse intestinal electrical stimulation (DPIES) on
      intestinal dysrhythmia and motility, and symptoms induced by vasopressin in
      conscious dogs. The study was performed in three postprandial sessions (control;
      vasopressin; DPIES) in six dogs with two pairs of electrodes chronically
      implanted on the serosal surface of the proximal jejunum and with a chronic
      duodenal fistula. A manometric catheter was advanced into the small intestine via
      the intestinal cannula. Motility and intestinal slow waves were recorded.
      Symptoms were assessed. During vasopressin infusion, the percentage of normal
      intestinal slow wave frequency was decreased (P < 0.01), reflected as a
      significant increase in the percentage of both bradygastria and tachygastria; the
      motility index decreased (P < 0.01) and the symptom score increased (P < 0.01).
      In the session of DPIES, the percentage of normal slow wave frequency was
      recovered (P < 0.05 vs vasopressin), attributed to a reduction in both
      bradyarrhythmia and tachyarrhythmia; the symptom score was reduced (P < 0.05 vs
      vasopressin); the motility index was not significantly increased. These results
      suggest that vasopressin induces intestinal dysrhythmia and emetic symptoms and
      inhibits intestinal motility. Dual pulse intestinal electrical stimulation is
      capable of improving intestinal dysrhythmia and emetic symptoms but not impaired
      intestinal motility induced by vasopressin.

PMID- 17509025
TI  - Bacterial infection-related morbidity and mortality in cirrhosis.
AB  - OBJECTIVES: Bacterial infections are acknowledged causes of morbidity and
      mortality in cirrhotic patients; yet, apart from spontaneous bacterial
      peritonitis, other infection issues have been understudied. We evaluated the
      existing medical data on infectious risks and related preventive and treatment
      data for cirrhotic patients. METHODS: Medical literature search through MEDLINE,
      using a variety of keywords focused on: (a) immunodeficiency parameters of
      cirrhosis and attempts at therapeutic reversal, (b) relative incidence of various
      focal infections and implications for prevention, and (c) specific pathogens
      posing a risk in cirrhosis and availability of preventive strategies. RESULTS:
      Immunodeficiency in cirrhosis is multifactorial and might not be reversed by
      isolated interventions. Epidemiologic data on the incidence of specific
      infections and risk factors are scarce, only Child-Pugh stage C being a common
      denominator. A variety of common, such as Staphylococcus aureus, Streptococcus
      pneumoniae, and Mycobacterium tuberculosis, as well as uncommon pathogens possess
      significant risks in cirrhosis. Certain aspects of these risks remain though
      unrecognized. CONCLUSIONS: To better understand the overall burden of bacterial
      infections on cirrhotic patients' survival, more data on preventive efficacy of
      pneumococcal vaccination, on the overall burden of tuberculosis, and the relative
      incidence of specific infections as endocarditis are warranted.

PMID- 17509026
TI  - Aberrant DNA methylation in non-neoplastic gastric mucosa of H. Pylori infected
      patients and effect of eradication.
AB  - BACKGROUND: Gene promoter methylation is an epigenetic event leading to gene
      silencing. This mechanism is particularly relevant in cancer since it can
      interfere with the activity of specific "suppressor" genes. AIM: To evaluate
      promoter methylation of CDH1, p16, APC, MLH1, and COX2 in patients with H. pylori
      (Hp) infection before and after eradication. METHODS: Fifty-seven dyspeptic
      outpatients who had never performed previous endoscopy or Hp testing and
      treatment underwent clinical interview, endoscopy with three paired gastric
      biopsy specimens from the antrum, angulus, and corpus, and (13)C-urea breath test
      (UBT). Biopsies were scored for the presence of Hp and intestinal metaplasia
      (IM). DNA methylation of five tumor-related genes (CDH1, p16, MLH1, APC, and
      COX2) was evaluated by methylation-specific PCR in each biopsy. Infected patients
      were given a standard eradicating treatment and, after 1 yr, underwent endoscopy
      with biopsies and UBT. RESULTS: Hp infection was found in 45 patients. IM was
      detected in 17 out of 45 (38%) infected patients. Mean number of methylated genes
      was 0, 1.1 +/- 0.9, and 1.6 +/- 0.9 among the 12 Hp-/IM-, the 28 Hp+/IM-, and the
      17 Hp+/IM+ patients, respectively (P < 0.0001). Specifically, promoter
      hypermethylation of CDH1, p16, APC, MLH1, and COX2 was found in 68%, 25%, 7%, 0%,
      and 14% of Hp+/IM- patients and in 71%, 29%, 35%, 12%, and 12% of Hp+/IM+
      patients. No significant difference was found among the three groups of patients
      as far as age, smoking, alcohol, meat and vegetable consumption, and family
      history of gastric cancer were considered. Twenty-three out of 45 (51%) infected
      patients underwent the 1-yr follow-up endoscopy: 17 out of 23 (74%) were
      successfully eradicated. After Hp eradication, CDH1, p16, and APC methylation
      significantly decreased while COX2 methylation completely disappeared.
      Conversely, MLH1 methylation did not change significantly in patients with IM.
      CONCLUSION: Hp infection is associated with promoter methylation of genes which
      are relevant in the initiation and progression of gastric carcinogenesis. While
      CDH1 methylation seems to be an early event in Hp gastritis, MLH1 methylation
      occurs late along with IM. Hp eradication is able to significantly reduce gene
      methylation thus delaying or reversing Hp-induced gastric carcinogenesis.

PMID- 17509027
TI  - Characterization of health related quality of life (HRQOL) for patients with
      functional bowel disorder (FBD) and its response to treatment.
AB  - BACKGROUND AND AIMS: Assessing health related quality of life (HRQOL) is becoming
      more important in research and clinical care. However, little information is
      available on the performance of HRQOL questionnaires for the functional bowel
      disorders (FBD). The aims of this study were to (a) understand the performance of
      the Sickness Impact Profile (SIP) and IBS-QOL for the functional bowel disorders
      at baseline and after treatment, (b) determine which HRQOL subscales best improve
      with treatment, (c) determine clinically meaningful improvement, and (d)
      determine the predictors of HRQOL at baseline and in response to treatment.
      METHODS: Women with moderate to severe FBD were evaluated using both medical
      (desipramine vs placebo) and psychological (cognitive-behavioral therapy vs
      education) treatments. Clinical and psychosocial questionnaires along with the
      SIP and IBS-QOL were given at baseline and after 12-wk treatment. RESULTS: (a)
      Patients with FBD experience functional limitations in social interactions, home
      management, and recreational activities, respond emotionally to the pain, feel
      helpless, out of control, depressed, and irritable, and perceive restrictions in
      lifestyle relating to toilet accessibility, and eating; (b) HRQOL is not
      different among the FBD diagnoses or IBS subgroups; (c) the IBS-QOL is more
      responsive to treatment than the SIP; (d) meaningful clinical improvement is 2.8
      points for SIP and 14 for IBS-QOL; and (e) improvement is demonstrated primarily
      in psychosocial rather than physical domains. In addition, we found that
      expectation of benefit is greater for taking a pill over a psychological
      intervention, and the predictive effects of abuse history and pain on outcome is
      mediated by psychosocial factors. CONCLUSIONS: The data support the value of the
      IBS-QOL over the SIP, and provide new information on the profile of impairment in
      FBD, and the ways in which medical and psychological treatments produce
      improvement in HRQOL.

PMID- 17509028
TI  - A randomized, double-blind, placebo-controlled study to assess efficacy and
      safety of 0.5 mg and 1 mg alosetron in women with severe diarrhea-predominant
      IBS.
AB  - OBJECTIVE: Alosetron is indicated for women with chronic, severe diarrhea
      predominant IBS (d-IBS) who have not responded adequately to conventional
      therapy. Constipation is the most common adverse event with alosetron treatment.
      Multiple dosing regimens were assessed in a randomized, double-blind, placebo
      controlled study (S3B30040) to determine efficacy, tolerability, and evaluate
      constipation rate. METHODS: 705 women with severe d-IBS were randomized to
      placebo, alosetron 0.5 mg once daily, 1 mg once daily, or 1 mg twice daily for 12
      wk. The primary end point was the proportion of week 12 responders (patients with
      moderate or substantial improvement in IBS symptoms) on the 7-point Likert Global
      Improvement Scale (GIS). Secondary end points were average rate of adequate
      relief of IBS pain and discomfort, and bowel symptom improvements. RESULTS: The
      proportion of GIS responders at week 12 (primary time point) was significantly
      greater in all alosetron groups compared with placebo (54/176 [30.7%], 90/177
      [50.8%], 84/175 [48%], and 76/177 [42.9%] for placebo, 0.5, 1 mg once daily, and
      1 mg twice daily alosetron groups, respectively; P< or = 0.02). Results were
      similar for the average adequate relief rate (treatment effects > or =12%, P< or
      = 0.038). Bowel symptoms were improved in all alosetron groups. Constipation was
      the most common adverse event (9%, 16%, and 19% patients in the 0.5 mg, 1 mg once
      daily, and 1 mg twice daily groups, respectively). One event of intestinal
      obstruction and one of ischemic colitis occurred in the 0.5 mg group, and one
      event of fecal impaction occurred in the 1 mg twice-daily group. All were self
      limited and resolved without sequelae. CONCLUSION: Alosetron 0.5 mg and 1 mg once
      daily as well as 1 mg twice daily are effective in providing global improvement
      in IBS symptoms, adequate relief of IBS pain and discomfort, and improvement in
      bowel symptoms in women with severe d-IBS. Lower dosing regimens resulted in a
      decreased constipation rate.

PMID- 17509029
TI  - Incidence rates of post-ERCP complications: a systematic survey of prospective
      studies.
AB  - OBJECTIVES: To provide health-care providers, patients, and physicians with an
      exhaustive assessment of prospective studies on rates of complications and
      fatalities associated with endoscopic retrograde cholangiopancreatography (ERCP).
      METHODS: We searched MEDLINE (1977-2006) for prospective surveys on adult
      patients undergoing ERCP. "Grey literature" was sought by looking at cited
      references to identify further relevant studies. Data on postprocedural
      pancreatitis, bleeding, infections, perforations, and miscellaneous events as
      well as their associated fatalities were extracted independently by two
      reviewers. Sensitivity analysis was performed to test for data consistency
      between multicenter versus single center studies, and old (1977-1996) versus
      recent (1997-2005) reports. RESULTS: In 21 selected surveys, involving 16,855
      patients, ERCP-attributable complications totaled 1,154 (6.85%, CI 6.46-7.24%),
      with 55 fatalities (0.33%, CI 0.24-0.42%). Mild-to-moderate events occurred in
      872 patients (5.17%, CI 4.83-5.51%), and severe events in 282 (1.67%, CI 1.47
      1.87%). Pancreatitis occurred in 585 subjects (3.47%, CI 3.19-3.75%), infections
      in 242 (1.44%, CI 1.26-1.62%), bleeding in 226 (1.34%, CI 1.16-1.52%), and
      perforations in 101 (0.60%, CI 0.48-0.72%). Cardiovascular and/or analgesia
      related complications amounted to 173 (1.33%, CI 1.13-1.53%), with 9 fatalities
      (0.07%, CI 0.02-0.12%). As compared with old reports, morbidity rates increased
      significantly in most recent studies: 6.27%versus 7.51% (P(c)= 0.029).
      CONCLUSIONS: ERCP remains the endoscopic procedure that carries a high risk for
      morbidity and mortality. Complications continue to occur at a relatively
      consistent rate. The majority of events are of mild-to-moderate severity.

PMID- 17509030
TI  - Risk factors for perianal Crohn's disease: the role of genotype, phenotype, and
      ethnicity.
AB  - OBJECTIVES: Perianal disease (PD) is a frequent complication of Crohn's disease
      (CD). The lack of association between PD and development of intestinal
      penetrating disease may suggest that PD is a distinct phenotype with specific
      genetic or clinical risk factors. This study was undertaken to evaluate the role
      of genotype, clinical, and demographic characteristics with PD. METHODS:
      Phenotypic data on 121 CD patients with PD and 179 patients without PD were
      carefully characterized. The patients were genotyped for disease-associated
      OCTN1/2 and NOD2/CARD15 variants and the TNF-alpha promoter polymorphisms.
      Analysis was performed to evaluate the differences in phenotype and genotype
      frequencies between the PD group and the non-PD group. RESULTS: PD was associated
      with rectal involvement (odds ratio [OR] 2.27, 95% CI 1.32-3.91) and with
      Sephardic (non-Ashkenazi) Jewish ethnicity (OR 1.71, 95% CI 1.02-2.9). No
      association was found among the studied OCTN, NOD2, TNF-alpha variants and the
      risk for PD. CONCLUSIONS: The strongest factor associated with PD is rectal
      inflammation. OCTN1/2, NOD2/CARD15, and TNF-alpha promoter variants do not play a
      role in the risk to PD in the Jewish Israeli population. The association of
      ethnicity with PD may suggest that there are as yet unknown genetic variants that
      are associated with PD.

PMID- 17509031
TI  - Systematic review of the risk of enteric infection in patients taking acid
      suppression.
AB  - CONTEXT: Proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RAs)
      have become the mainstay of therapy in acid-related upper gastrointestinal
      disorders. There have been concerns raised about the possible association of PPIs
      with enteric infections. OBJECTIVE: We conducted a systematic review to evaluate
      any association between acid suppression and enteric infection. We also assessed
      differences between types of enteric infections and the type of acid suppression.
      DATA SOURCES: Electronic searches of MEDLINE (1966-2005), EMBASE (1988-2005), and
      CINAHL (1982-2005) were undertaken using a combination of subject headings and
      text words related to PPI therapy, H(2)RAs, and enteric infections. STUDY
      SELECTION: All observational studies were eligible, including cross-sectional,
      case control, and cohort studies that evaluated risk of enteric infection
      associated with antisecretory therapy. Eligibility assessment was made by two
      independent researchers. DATA EXTRACTION: Information on study design, patient
      population, type of acid suppression, type of infection, and outcomes was
      collected. The odds ratio (OR) of taking acid suppression therapy in cases and
      controls was calculated and results were synthesized using a random effects model
      (DerSimonian and Laird, Stats direct version 2.4.4). DATA SYNTHESIS: A total of
      12 papers evaluating 2,948 patients with Clostridium difficile were included in
      the review. There was an increased risk of taking antisecretory therapy in those
      infected with C. difficile (pooled OR 1.94, 95% CI 1.37-2.75). There was
      significant heterogeneity between the studies (P= 0.0006) that was not explained
      by planned subgroup analysis. The association was greater for PPI use (OR 1.96,
      95% CI 1.28-3.00) compared with H(2)RA use (OR 1.40, 95% CI 0.85-2.29). A total
      of six studies evaluated Salmonella, Campylobacter, and other enteric infections
      in 11,280 patients. There was an increased risk of taking acid suppression in
      those with enteric infections (OR 2.55, 95% CI 1.53-4.26). There was significant
      heterogeneity between the studies (P < 0.0001) that was not explained by subgroup
      analysis. The association was greater for PPI use (OR 3.33, 95% CI 1.84-6.02)
      compared with H(2)RA use (OR 2.03, 95% CI 1.05-3.92). CONCLUSION: There is an
      association between acid suppression and an increased risk of enteric infection.
      Further prospective studies on patients taking long-term acid suppression are
      needed to establish whether this association is causal.

PMID- 17509032
TI  - Light to moderate alcohol consumption is associated with lower frequency of
      hypertransaminasemia.
AB  - OBJECTIVES: The effect of light to moderate alcohol consumption on the liver is
      controversial. To determine the association between light to moderate alcohol
      consumption and frequency of hypertransaminasemia, a cross-sectional and a
      subsequent longitudinal cohort study were conducted using annual health checkup
      data at a Japanese workplace. METHODS: We analyzed 1,177 male subjects (age 20
      59) without HCV or HBV infection or other chronic liver diseases. To determine
      the association between alcohol consumption (none or minimal <70 g/wk, light > or
      =70 g and <140 g/wk, moderate > or =140 g and <280 g/wk, excessive > or =280
      g/wk) and hypertransaminasemia, we performed multiple logistic regressions. We
      then followed 326 subjects without a history of fatty liver or
      hypertransaminasemia up to 5 years for incidental hypertransaminasemia and
      performed Cox proportional hazard regressions. RESULTS: Excess alcohol
      consumption was associated with increased odds of hypertransaminasemia (adjusted
      odds ratio [AOR]versus none or minimal consumption 1.4[1.1-1.93], P= 0.023).
      There was significant interaction between age group and alcohol consumption (P <
      0.01). In the younger group, moderate consumption was associated with decreased
      odds (AOR 0.5 [0.3-0.9], P= 0.032), while in the older group, light consumption
      was associated with decreased odds (AOR 0.6 [0.4-1.0], P= 0.036) and excess
      consumption was associated with increased odds (AOR 1.6 [1.1-2.3], P= 0.014) of
      hypertransaminasemia. During follow-up, moderate consumption was associated with
      decreased incidence of hypertransaminasemia versus none or minimal consumption
      (adjusted hazard ratio 0.4 [0.1-0.9], P= 0.02). CONCLUSION: Light to moderate
      alcohol consumption may protect against the development of hypertransaminasemia
      among male subjects without other liver conditions. Further studies are required
      before recommending light to moderate alcohol consumption.

PMID- 17509033
TI  - Stepwise radical endoscopic resection of the complete Barrett's esophagus with
      early neoplasia successfully eradicates pre-existing genetic abnormalities.
AB  - OBJECTIVES: Malignant transformation of Barrett's mucosa is associated with the
      accumulation of genetic alterations. Stepwise radical endoscopic resection of the
      Barrett's segment with early neoplasia is a promising new treatment resulting in
      complete re-epithelialization of the esophagus with neosquamous epithelium. It is
      unknown whether radical resection also eradicates genetic abnormalities. The aim
      of this study was to prospectively evaluate whether genetic abnormalities as
      found in the Barrett's segment before radical resection are effectively
      eradicated and absent in the neosquamous epithelium. METHODS: Nine patients with
      early neoplasia who successfully underwent radical resection were included.
      Immunohistochemistry (IHC) was performed to assess p53 protein overexpression.
      DNA fluorescent in-situ hybridization was (DNA-FISH) performed for evaluation of
      numerical abnormalities of chromosomes 1 and 9, and losses of p16 and p53.
      Immunohistochemistry and DNA-FISH were performed on endoscopic resection
      specimens of the neoplasia and on follow-up biopsies of the neosquamous
      epithelium. RESULTS: DNA-FISH and IHC showed alterations in the pretreatment
      samples of all patients. All showed aneusomy of chromosome 1 and 9. Loss of p16
      and p53 were seen in 6 and 8 patients. IHC showed intense p53 nuclear staining in
      seven patients. Post-treatment biopsies showed neosquamous epithelium with a
      normal diploid signal count for all DNA-FISH probes and normal IHC stainings in
      all patients. CONCLUSIONS: Radical resection of Barrett's esophagus with early
      neoplasia successfully eradicates pre-existing genetic abnormalities and results
      in neosquamous epithelium without these genetic abnormalities.

PMID- 17509034
TI  - Optimal thresholds and discriminatory power of 48-h wireless esophageal pH
      monitoring in the diagnosisof GERD.
AB  - BACKGROUND: The discriminative power of 48-h wireless esophageal pH monitoring in
      the diagnosis of gastroesophageal reflux disease has not been clearly
      demonstrated, and the cutoff level for esophageal acid exposure generating the
      optimal sensitivity and specificity is unknown. SUBJECTS AND Patients with
      typical reflux symptoms and a distinct response to acid suppressive medication
      METHODS: underwent upper GI endoscopy followed by 48-h wireless esophageal pH
      studies with the pH electrode placed 6 cm above the squamocolumnar junction. The
      results were compared to those obtained in 55 healthy controls. Sensitivity,
      specificity, and thresholds for esophageal acid exposure were analyzed using
      receiver operating characteristic (ROC) curves. RESULTS: The patient population
      consisted of 64 patients, 25 women and 39 men, with a median age of 48 yr.
      Analysis of the area under the ROC curve showed that, for all patients as well as
      for subgroups of patients with (N = 33) and without (N = 31) esophagitis, the
      total percent time with pH <4 for the 48-h study period was the best parameter to
      discriminate patients from controls. Analysis of acid exposure for day 1, day 2,
      or using the day with the highest acid exposure did not improve the diagnostic
      accuracy. A test specificity in the range of 90-95% resulted in a cutoff level of
      3.6-4.4% of the total time with pH <4 for the 48-h period. This threshold
      generated a test sensitivity of 59-64% in all patients, 76-79% for patients with
      esophagitis and 42-48% in patients with no esophagitis. CONCLUSIONS: The total
      percentage of time that esophageal pH was less than 4 for the entire 48-h study
      period was the parameter that best discriminated patients with typical reflux
      symptoms from healthy controls, and to achieve a specificity of 90-95% a cutoff
      level of 4% is recommended. The low sensitivity of wireless pH recording in
      patients without erosive esophagitis substantially reduces the clinical value of
      the test.

PMID- 17509035
TI  - The effect of ABCG2 V12M, Q141K and Q126X, known functional variants in vitro, on
      the disposition of lamivudine.
AB  - AIMS: To evaluate the effects of three ABCG2 variants (Q141K, V12M and Q126X),
      which are known to have altered transport properties in vitro, on the disposition
      of lamivudine in healthy subjects. METHODS: To evaluate whether lamivudine is a
      substrate of ABCG2, intracellular accumulation and vectorial transport of 3H
      lamivudine were determined in MDCK-ABCG2 cells. The pharmacokinetic parameters of
      lamivudine were compared among subjects with four different ABCG2 genotypes,
      including wild type (seven subjects), K141/K141 (six subjects), Q126/Stop126
      (four subjects) and M12/M12 (five subjects) after a single oral dose of 100 mg
      lamivudine. RESULTS: The intracellular accumulation of lamivudine in MDCK-ABCG2
      cells was significantly lower than that in MDCK-mock cells, but fumitremorgin C
      reversed the intracellular lamivudine concentration to that of MDCK-mock cells.
      The ABCG2-mediated transport of lamivudine was saturable and the values of Km and
      Vmax were 216.5 +/- 58 microm and 20.42 +/- 2.9 nmol h(-1) per 10(6) cells,
      respectively. After lamivudine administration to healthy subjects, the AUC of
      lamivudine showed no difference among subjects with different ABCG2 genotypes;
      2480 +/- 502, 2207 +/- 1019, 2422 +/- 239, 2552 +/- 698 ng h(-1) ml(-1) for wild
      type, K141/K141, Q126/Stop126 and M12/M12 genotype, respectively (P = 0.85). The
      estimated 95% confidence intervals for the mean difference between K141/K141,
      Q126/Stop126, M12/M12 and wild as reference were (-1053, 507), (-555, 439) and (
      552, 696), respectively. No other pharmacokinetic parameters were estimated to be
      significantly different among four different ABCG2 genotypes tested. CONCLUSIONS:
      Lamivudine appeared to be a substrate of ABCG2 in vitro, but the disposition of
      lamivudine was not significantly influenced by known in vitro functional variants
      of ABCG2, Q141K, V12M and Q126X in healthy subjects.

PMID- 17509036
TI  - Diclofenac and acute myocardial infarction in patients with no major risk
      factors.
AB  - AIMS: To explore further a recent finding that long-term users of diclofenac are
      at increased risk of acute myocardial infarction (AMI) similar to users of
      rofecoxib and celecoxib. METHODS: Using the General Practice Research Database,
      we conducted three separate nested case-control studies of three nonsteroidal
      anti-inflammatory drugs (NSAIDs) where use started after 1 January 1993-
      diclofenac, ibuprofen and naproxen. Cases of AMI were identified between 1
      January 1993 and 31 December 2000. Relative risk (RR) estimates for AMI in
      patients with no major clinical risk factors were determined for each NSAID
      according to number of prescriptions received compared with one prescription.
      Results were adjusted for variables possibly related to risk of AMI. RESULTS:
      There was no material elevation of AMI risk according to the number of
      prescriptions for ibuprofen [RRs and 95% confidence intervals (CIs) 1.0 (0.6,
      1.6) and 1.7 (0.9, 3.1) for use of 10-19 and 20+ prescriptions, respectively,
      compared with one prescription] or naproxen [RRs 1.0 (0.5, 2.2) and 2.0 (0.9,
      4.5) for use of 10-19 and 20+ prescriptions, respectively]. However, a
      substantial increased risk similar to that obtained in our prior study was found
      in patients who received >or=10 prescriptions for diclofenac [RRs 1.9 (1.3, 2.7)
      and 2.0 (1.3, 3.0) for use of 10-19 and 20+ prescriptions, respectively].
      CONCLUSIONS: Extensive use of diclofenac substantially increases the risk of AMI.
      There is little suggestion of such an effect in users of ibuprofen and naproxen.

PMID- 17509037
TI  - Dose-dependent acute excessive weight gain and metabolic changes in a drug-naive
      patient on risperidone are reversible with discontinuation: a case report.

PMID- 17509038
TI  - When a placebo is not a 'placebo': a placebo effect on postprandial glycaemia.
AB  - AIMS: Placebo effects in clinical trials remain uncertain. To investigate a
      placebo effect on acute postprandial plasma glucose, we conducted a follow-up
      investigation on a previous study. METHODS: The effect of placebo (9 g
      encapsulated cornstarch +500 ml water, taken at -40 min) on the plasma glucose
      response to a 75-g oral glucose tolerance test (OGTT) was assessed in a previous
      study in 12 healthy subjects (gender, five male, seven female; age 27 +/- 6
      years; body mass index 24 +/- 3.4 kg m(-2)). This was compared with the effect of
      a water control (500 ml water taken alone at -40 min) on the same outcome in the
      same subjects in a follow-up study. RESULTS: Cornstarch placebo decreased plasma
      glucose area under the curve during the 75-g OGTT by 28% [Delta (95% confidence
      interval) -63.3 min mmol(-1) l(-1) (-218.33, 91.66), P < 0.02] compared with the
      water control (P < 0.05). CONCLUSIONS: Postprandial plasma glucose outcomes may
      be vulnerable to placebo effects.

PMID- 17509040
TI  - Anti-factor Xa activity of enoxaparin administered at prophylactic dosage to
      patients over 75 years old.
AB  - AIMS: Major bleeding complications with low-molecular-weight heparin (LMWH)
      treatment have been reported both in clinical studies and during postmarketing
      surveillance. Monitoring of antifactor Xa (anti-Xa) activities is therefore
      recommended in special populations often predisposed to renal impairment. The
      PROPHRE.75 study was conducted to estimate the distribution parameters of anti-Xa
      activity in the elderly. METHODS: PROPHRE.75 was a prospective study of a cohort
      of consecutive patients aged >75 years and treated with 4000 IU of enoxaparin
      once daily for venous thromboembolism prophylaxis. Dosing history and
      measurements of anti-Xa activity in sparse samples were recorded throughout
      treatment. The covariates included weight, gender, age, renal function, medical
      history and concomitant medication. Population parameters and interindividual
      variability were estimated using NONMEM V software. RESULTS: Anti-Xa activity was
      studied in 189 patients (mean age 82 +/- 5 years, 22% weighing <50 kg, 50%
      presenting renal impairment according to the Cockcroft and Gault formula). A
      first-order input two-compartment model best fitted the data. Clearance was
      significantly related to body weight and creatinine clearance based on the
      simplified Modification of Diet in Renal Disease formula, central volume being
      related to body weight. According to individual Bayesian estimations, 4% of
      patients presented with a peak anti-Xa activity >1.0 IU ml(-1), but this group
      did not include the sole patient experiencing a major bleed (0.53%). CONCLUSIONS:
      Systematic monitoring of anti-Xa activity in elderly patients treated with
      enoxaparin at prophylactic doses does not seem to be necessary to prevent the
      occurrence of major bleeding.

PMID- 17509042
TI  - Nurse specialist led flexible sigmoidoscopy in an outpatient setting.
AB  - OBJECTIVE: There has been an increasing demand for diagnostic flexible
      sigmoidoscopy. In order to improve our diagnostic services, we established a
      nurse specialist led flexible sigmoidoscopy clinic in 1999. The aim of this study
      was to review the outcomes of this service between 1999 and 2004. METHOD: The
      following information was collected prospectively: source of referral, presenting
      symptoms, the result of the flexible sigmoidoscopy, depth of insertion, the
      follow-up plan and complications. RESULTS: A total of 3956 patients had a
      flexible sigmoidoscopy performed between 1999 and 2004. The presenting symptoms
      were as follows: rectal bleeding (RB) in 1915 patients, change of bowel habit
      (CBH) in 421 patients, RB+CBH in 814 patients. The depth of insertion of the
      sigmoidoscope was as follows: rectum in 85 patients, sigmoid colon in 595
      patients, descending colon in 1969 patients, splenic flexure in 958 patients and
      transverse colon in 311 patients. The findings at sigmoidoscopy were as follows:
      normal in 1560 patients, cancer in 132 patients, inflammatory bowel disease in
      276 patients, polyps in 415 patients, diverticular disease in 584 patients and
      haemorrhoids in 926 patients. Two patients sustained an iatrogenic rectal
      perforation. CONCLUSION: The nurse specialist led flexible sigmoidoscopy clinic
      offers an efficient and safe diagnostic service for patients presenting with
      colorectal symptoms.

PMID- 17509041
TI  - Pharmacokinetic/pharmacodynamic evaluation of urinary cortisol suppression after
      inhalation of fluticasone propionate and mometasone furoate.
AB  - AIM: Fluticasone propionate (FP) and mometasone furoate (MF) are inhaled
      corticosteroids that possess a high ratio of topical to systemic activity. The
      systemic bioavailability of MF has been claimed to be minimal (1%). FP has been
      shown to exhibit the same degree of systemic effects, but its systemic
      availability is between 13 and 17%. We hypothesize that FP and MF have comparable
      systemic availabilities that can explain their potential to cause systemic
      effects. METHODS: Steady-state FP and MF trough plasma samples were determined
      from a clinical study by Fardon et al. in patients with persistent asthma (forced
      expiratory volume in 1 s = 91%). The percent plasma protein binding of FP and MF
      was measured using ultracentrifugation. Free FP plasma concentrations were
      normalized for their differences in receptor binding affinity compared with MF
      and linked to overnight urinary cortisol/creatinine with an inhibitory E(max).
      RESULTS: A plot of steady-state FP and MF total trough plasma concentrations vs.
      dose showed that both drugs exhibit dose linearity. MF has comparable
      bioavailability to FP based on the steady-state concentrations observed for the
      different doses. The free plasma concentration producing 50% of urinary cortisol
      suppression (IC(50)) for MF was not statistically different from the free,
      normalized IC(50) for FP. CONCLUSION: FP and MF have similar pulmonary deposition
      and the same potential to cause systemic side-effects due to their similar IC(50)
      values. The observed urinary cortisol suppression of FP and MF is in agreement
      with their systemic availability, their differences in plasma protein binding and
      receptor binding affinity.

PMID- 17509043
TI  - Malignancy in an old pilonidal sinus.

PMID- 17509044
TI  - Self-everting ileostomy.
AB  - OBJECTIVE: Self-everting ileostomy. METHOD: After delivering the small bowel
      through the trephine wound the bowel is opened and with time the mucosa migrates
      to the skin edge forming a spouted ileostomy. RESULTS: Five patients underwent
      the self-everting ileostomy with no stomal complications experienced. The end
      result is indistinguishable from a primarily sutured stoma. CONCLUSION: The self
      everting ileostomy can be a useful technique to get out of a difficult situation.

PMID- 17509045
TI  - The 2-week wait referral system, etc.: flogging a dead horse?

PMID- 17509046
TI  - An uncommon finding: a retrorectal Schwannoma.

PMID- 17509047
TI  - Delayed diagnosis of rhabdomyoblastoma: a cautionary tale.

PMID- 17509048
TI  - Laparoscopic appendicectomy: a training model for laparoscopic right
      hemicolectomy?
AB  - OBJECTIVE: To analyse the outcome of laparoscopic appendicectomy and right
      hemicolectomy and see if the surgical approach to the former can be applied to
      the latter. METHOD: A prospective electronic laparoscopic database identified 330
      appendicectomies and 78 right hemicolectomies (using this approach) between 1996
      and 2005. RESULTS: Three hundred and thirty patients (188 males: median age 38
      years, range 17-74 years) underwent laparoscopic appendicectomy; 270 (82%) were
      performed by trainees (higher surgical trainee 71%, basic surgical trainee 12%).
      The median operative time for trainees was 35 min (14-75 min) with a conversion
      rate 2%. There were no intra-operative complications. The postoperative
      complication rate excluding minor wound infection (5.5%) was 1.5%. There were no
      deaths. The median hospital stay was 2 days (1-15 days). The 30-day readmission
      rate was 1%. Seventy-eight patients (23-93 years) underwent laparoscopic right
      hemicolectomy during 2004/5; trainees performed parts thereof in the majority or
      all of the surgery in 25 cases. The median operation time was 55 min: trainees
      115 (65-145 min). There was one conversion. The median hospital stay was 4 days
      (2-23 days) falling to 3 for the last 20 operations (1-8 days). There were two
      readmissions for wound sepsis and small bowel obstruction and three deaths
      (3.8%): anastomotic leak (one), C difficile infection leading to renal failure
      (one) and duodenal perforation (one). CONCLUSION: Laparoscopic appendicectomy is
      a safe, predictable, easily learnt operation and an ideal model for learning the
      skills and principles required for more advanced laparoscopic colorectal
      interventions and in particular, right hemicolectomy.

PMID- 17509049
TI  - Sacral neuromodulation in patients with faecal incontinence: results of the first
      100 permanent implantations.
AB  - OBJECTIVE: Faecal incontinence (FI) is a socially devastating problem. Sacral
      nerve modulation (SNM) has proven its place in the treatment of patients with FI.
      In this study, the first 100 definitive SNM implants in a single centre have been
      evaluated prospectively. METHOD: Patients treated between March 2000 and May 2005
      were included. Faecal incontinence was defined as at least one episode of
      involuntary faecal loss per week confirmed by a 3-week bowel habit diary.
      Patients were eligible for implantation of a permanent SNM when showing at least
      a 50% reduction in incontinence episodes or days during ambulatory test
      stimulation. Preoperative workup consisted of an X-defaecography, pudendal nerve
      terminal motor latency measurement, endo-anal ultrasound and anal manometry. The
      follow-up visits for the permanent implanted patients were scheduled at 1, 3, 6
      and 12 months and annually thereafter. The bowel habit diary and anal manometry
      were repeated postoperatively during the follow-up visits. RESULTS: A total of
      134 patients were included and received a subchronic test stimulation. One
      hundred patients (74.6%) had a positive test stimulation and received a
      definitive SNM implantation. The permanent implantation group consisted of 89
      women and 11 men. The mean age was 55 years (range 26-75). The mean follow-up was
      25.5 months (range 2.5-63.2). The mean number of incontinence episodes decreased
      significantly during the test stimulation (baseline, 31.3; test, 4.4; P < 0.0001)
      and at follow-up (36 months postoperatively, 4.8; P < 0.0001). There was no
      significant change in the mean anal resting pressure. The squeeze pressures were
      significantly higher at 6 months (109.8 mmHg; P = 0.03), 12 months (114.1 mmHg; P
      = 0.02) and 24 months postoperatively (113.5 mmHg; P = 0.007). The first
      sensation, urge and maximum tolerable volume did not change significantly. Twenty
      one patients were considered late failures and received further treatment.
      CONCLUSION: Sacral neuromodulation is an effective treatment for FI. The medium
      term results were satisfying.

PMID- 17509050
TI  - Excision of residual skin tags during stapled anopexy does not increase
      postoperative pain.
AB  - OBJECTIVE: We studied whether excision of residual external skin tags causes
      additional pain in patients undergoing a stapled anopexy for muco-anal prolapse.
      METHOD: Seventeen patients in whom skin tags had been excised were compared with
      24 patients having no excision. The patients were selected from a prospective
      database of haemorrhoid surgery if they had submitted a diary with self-reported
      postoperative pain scores as well as a self-reported symptom questionnaire
      preoperatively and postoperatively. The tags were excised with preservation of
      the subdermal fascia. RESULTS: There were 41 patients who fulfilled the criteria
      for inclusion. Seventeen (group 1) had tags excised and 24 (group 2) did not.
      Fifty-nine per cent in group 1 and 67% in group 2 experienced preoperative
      prolapse needing manual reposition. The mean height of the staple line was 2 cm
      above the dentate line in both groups. Daily average postoperative pain recorded
      as the sum of a self-reported VAS rating over 14 days was 26 points in both
      groups. The peak pain experienced was 42 and 43 points respectively (not
      significant). Resolution of postoperative pain over 14 days was identical. The
      preoperative and postoperative symptom score was comparable in both groups.
      CONCLUSION: Excision of anal skin tags should be carried out at the time of
      stapled anopexy.

PMID- 17509051
TI  - Crohn's disease: systematic review of assessment of disease severity and its
      relevance to surgery.
AB  - BACKGROUND: The aims of treatments for Crohn's disease are symptom control by
      medical or surgical means and improvement in health-related quality of life
      (HRQOL). A wide number of classification systems, instruments of disease activity
      measurement (DAM) and HRQOL are available, but few are used in routine surgical
      practice. OBJECTIVE: To review the validity of DAM and HRQOL instruments and
      their applicability to surgically treated patients. METHOD: A systematic
      literature search was undertaken to identify these instruments. Qualifying
      articles were used to determine the construct, content and criterion validity of
      the instruments identified with respect to surgically treated patients. RESULTS:
      Thirteen disease activity indices and 11 HRQOL assessment tools were identified.
      Construct validity was demonstrated throughout but concerns of content and
      criterion validity were noted. CONCLUSION: None of the current disease activity
      or HRQOL tools can be used without potential bias in a trial of surgical vs
      medical therapy as the items included favour the outcomes experienced following
      medical therapy. A more balanced assessment tool in the setting of a
      multidisciplinary trial is needed.

PMID- 17509052
TI  - The nature of local recurrence after colorectal cancer resection.
AB  - OBJECTIVE: Local recurrence (LR) after rectal cancer resection has long been
      regarded as a particular problem, its incidence having been high. This study aims
      to determine the reasons why. METHOD: A prospective record was kept of all 887
      cases of colorectal adenocarcinoma referred to one surgeon between 1989 and 2000.
      Of these, 802 underwent major resection. They were followed up for 5 years or
      until death. RESULTS: There was no significant difference between LR rates
      throughout the colorectum (P = 0.74). LR was significantly related to tumour
      grade (P < 0.001) and to tumour stage (P < 0.001), but not to the need to resect
      involved adjacent structures (P = 0.08), nor, after restorative rectal resection,
      to the distal margin of clearance (P = 0.97). A difference became apparent
      between recurrence resulting from tumour left in or implanted into the operation
      field and tumour resulting from pre-excision metastasis, here called,
      respectively, technique-related (TLR) and pre-excision metastatic (MLR) local
      recurrence. MLR was significantly related to tumour stage (P < 0.001), while TLR
      was not. Some TLR can be curatively excised. CONCLUSION: Rectal LR is no more
      common than colonic LR. There may be practical merit in discriminating between
      TLR and MLR.

PMID- 17509053
TI  - Normal ranges for anorectal manometry and sensation in women of reproductive age.
AB  - OBJECTIVE: To derive a range of normal values for anal sphincter resting and
      squeeze pressure, and anorectal sensation in healthy women without anorectal
      disease before and after their first childbirth. METHOD: Nulliparous women
      undergoing anal physiology testing in the third trimester of pregnancy and 12
      weeks after delivery. All were asked to undergo anal manometry and anorectal
      electrosensation testing. Maximum resting pressure, maximum squeeze pressure and
      anal thresholds to electrical current were assessed at 1 cm intervals down the
      anal canal. Rectal electrosensitivity thresholds were assessed 10 cm from the
      anal verge. RESULTS: A total of 286 women attended for antenatal investigations
      and 161 (56%) returned postpartum. The anal canal length was 3.9 +/- 0.6 cm
      antenatally and 3.9 +/- 0.6 cm postnatally. During pregnancy the 95% normal range
      for anal resting and squeeze pressures, anal and rectal sensation were 29-90
      mmHg, 50-163 mmHg, 2-31 mA and 3-33 mA respectively. Post delivery the 95% normal
      ranges were 27-98 mmHg, 43-156, 2-12 mA and 0.1-34 mA respectively. Both
      antenatally and postnatally the manometry and sensitivity values were similar in
      women with and without bowel symptoms. CONCLUSION: This study is the largest
      series of normative data for anal manometry, and anorectal sensation in women
      before and after their first delivery. The antenatal values can serve to
      represent ranges for nulliparous women and the postnatal values ranges in
      primiparous women.

PMID- 17509054
TI  - Vitamin B12 deficiency following restorative proctocolectomy.
AB  - OBJECTIVE: Restorative proctocolectomy (RP) involves terminal ileal resection and
      formation of a small bowel reservoir that predisposes to bacterial overgrowth. It
      was anticipated that these patients would be at risk of vitamin B12 deficiency.
      METHOD: Vitamin B12 levels were measured sequentially in 171 patients who
      underwent RP. Prospective results were obtained from all 20 patients undergoing
      pouch formation after the commencement of the study. Further results were
      obtained retrospectively from case notes and computerized laboratory records of
      the 151 patients who underwent RP prior to the commencement of the study and
      these were correlated with the results of follow-up samples taken prospectively
      from the same patients after the commencement of the study. The median age of the
      patients was 40 years (range: 13-67) and the median duration of follow up was 5.4
      years (range: 1-12). Patients with an abnormally low serum B12 level underwent
      both a Schilling and a hydrogen breath test. Eight of these patients were then
      treated with oral vitamin B12. RESULTS: Abnormally low serum B12 levels were
      found in 25% of patients. Forty per cent of our patient group had three or more
      sequential B12 measurements and of these, 66% showed steadily declining B12
      levels. Ninety-four per cent of patients with low B12 had a normal Schilling test
      and were negative for bacterial overgrowth. CONCLUSION: Subnormal vitamin B12
      levels develop in almost one-quarter of patients after pouch surgery. The exact
      mechanism for B12 deficiency in these patients is uncertain. In the majority of
      patients undergoing RP, vitamin B12 levels fall on sequential measurement. Serum
      B12 levels should be measured during follow up and pouch patients with subnormal
      B12 levels, should see them successfully restored to a normal value after
      treatment with oral B12 replacement therapy.

PMID- 17509055
TI  - Digital superficial angiomyxoma.
AB  - Superficial angiomyxoma is a rare, distinctive cutaneous soft-tissue neoplasm,
      which shows a prominent myxoid matrix with numerous blood vessels. This condition
      usually presents with a nodular lesion on the trunk, head and neck, or the
      genital region. We describe a case of superficial angiomyxoma, which presented at
      an unusual digital location while also demonstrating the features of
      transepidermal elimination, and which mimicked a digital myxoid cyst.

PMID- 17509056
TI  - Naevus comedonicus: a spectrum of body involvement.
AB  - Naevus comedonicus (NC) is a rare developmental anomaly, with < 200 cases
      reported in the literature. It usually occurs on the face, neck or chest,
      appearing as groups of closely arranged dilated follicular openings with keratin
      plugs. Several associations have been made in the literature. We review the
      current literature, emphasizing the clinical features, associated conditions and
      therapeutic options.

PMID- 17509057
TI  - The mRNA expression and promoter methylation status of the p16 gene in colony
      forming cells with high proliferative potential in patients with psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic and relapsing inflammatory disease of the skin
      associated with various immune abnormalities. It is tempting to speculate that
      the dysfunctional immunity may influence the haematopoietic microenvironment or
      haematopoiesis in psoriasis. However, direct evidence of involvement of bone
      marrow haematopoietic cells in the pathogenesis of psoriasis is lacking. AIM: To
      investigate the proliferative activity of haematopoietic cells of patients with
      psoriasis and a link between the promoter methylation status and transcriptional
      activity of the p16 gene and the colony-forming ability of high proliferative
      potential colony-forming cells (HPP-CFCs). METHODS: Marrow mononuclear cells were
      isolated from the bone marrow of patients with psoriasis and normal controls by
      density gradient centrifugation. A comparison of HPP-CFC colony formation counts
      between patients with psoriasis and normal controls was carried out by colony
      forming assays of HPP-CFCs in methylcellulose semisolid culture medium in vitro.
      Subsequently, genomic DNA and RNA in HPP-CFCs were isolated, and mRNA expression
      and p16 promoter methylation status were studied by reverse transcriptase PCR and
      methylation-specific PCR (MSP), respectively. RESULTS: In comparison with normal
      controls, patients with psoriasis showed less HPP-CFC colony formation in the
      methycellulose semisolid culture system, and showed upregulated mRNA
      transcriptional level and downregulated promoter methylation of p16. CONCLUSIONS:
      Our data demonstrate for the first time the abnormal proliferative activity of
      haematopoietic cells in patients with psoriasis and a profound link between the
      promoter methylation status and transcriptional activity of p16 and the colony
      forming ability of HPP-CFCs, suggesting that haematopoietic cells are involved in
      psoriasis.

PMID- 17509058
TI  - Does deprivation of area of residence influence the incidence, tumour site or T
      stage of cutaneous malignant melanoma? A population-based and clinical database
      study.
AB  - This study aimed to document the incidence of malignant melanoma at specific
      subsites in men and women, stratified by deprivation of area of residence in
      southeast England, and to explore the association between deprivation and tumour
      thickness at diagnosis. Data were extracted on 6468 cases from the Thames Cancer
      Registry for the years 1998 to 2002, and data on, and 508 cases were extracted
      from the clinical database of the Skin Tumour Unit, St Thomas' Hospital, for the
      years 1996 to 2004. The postcode of residence was used to assign quintiles of
      deprivation based on the income domain stated in the Indices of Deprivation 2000.
      For both males and females, the incidence was higher for those living in the most
      affluent areas. The trunk was the most common site in males and the lower limbs
      in females. All sites showed an affluence gradient, although this was least
      pronounced for head and neck tumours. Distribution of T stage at diagnosis did
      not differ by deprivation of area of residence.

PMID- 17509059
TI  - Eyelash and eyebrow trichomegaly induced by interferon-alfa 2a.

PMID- 17509060
TI  - Capecitabine-induced diffuse palmoplantar keratoderma: is it a sequential event
      of hand-foot syndrome?
AB  - Capecitabine was developed as a prodrug of 5-fluorouracil (FU), with the goal of
      improving tolerability and intratumour drug concentrations through tumour
      specific conversion to the active drug against numerous types of neoplasms. The
      most frequent adverse cutaneous reaction associated with capecitabine is hand
      foot syndrome (HFS), presented with symmetrical erythema, dysaesthesia, and
      desquamation on the palms and soles. Acquired palmoplantar keratoderma (PPK) can
      occur in various dermatoses associated with metabolic abnormalities,
      malignancies, and toxic agents. However, there has been no report of PPK after
      capecitabine chemotherapy. We report two cases of diffuse PPK, which developed in
      patients with metastatic breast cancer after one cycle of capecitabine
      chemotherapy. Because oral capecitabine is increasingly used for various solid
      tumours, clinicians should be aware that keratoderma can develop during
      capecitabine chemotherapy as a sequential event of HFS.

PMID- 17509061
TI  - Serum interleukin-18 in patients with chronic ordinary urticaria: association
      with disease activity.
AB  - Interleukin (IL)-18 is a pleiotropic cytokine, which may play a role in
      autoimmune and allergic disorders. Serum IL-18 levels were measured in 34
      patients with chronic ordinary urticaria (COU) and 17 normal subjects. In vivo
      and in vitro assays for histamine-releasing factors, an autologous serum skin
      test (ASST) and a basophil histamine release assay were also performed for all
      patients with COU. Serum IL-18 concentration was not significantly different
      between patients with COU and normal subjects (mean+/-standard error of the mean
      246.47+/-18.40 pg/mL vs. 213.88+/-22.24 pg/mL), and no significant difference was
      found between ASST-positive and ASST-negative patients. However, in ASST-positive
      patients, IL-18 levels paralleled clinical severity scores and showed a tendency
      to correlate with in vitro histamine release. The increased IL-18 levels in the
      ASST-positive patients with most active chronic urticaria may reflect stronger
      immune system activation and possibly an involvement of IL-18 as a direct
      histamine-releasing factor.

PMID- 17509062
TI  - Lichen planus induced by radiotherapy.

PMID- 17509063
TI  - Increased glucose uptake by keratoacanthoma detected by positron emission
      tomography.

PMID- 17509064
TI  - Kaposi's sarcoma as a Kobner phenomenon in a patient with bullous pemphigoid and
      sarcoidosis.

PMID- 17509065
TI  - Effect of loading time on the success of complete mandibular titanium implant
      retained overdentures: a systematic review.
AB  - OBJECTIVES: The aim of this review was to compare conventional against
      early/immediate loading protocols of implant-retained overdentures (IOD) in the
      edentulous mandible. MATERIAL AND METHODS: Medline search via Ovid to extract
      prospective comparative studies on trials comparing the effect of timing of
      loading initiation on the success of mandibular IOD. The outcome of major
      interest was marginal bone loss. Probing depth, plaque, bleeding index and
      mobility were also assessed. Indices at 12 and 24 months were compared and
      changes assessed. Outcomes were entered into RevMan (version 4.2.5) for meta
      analysis. RESULTS: Of 239 articles, only nine trials fulfilled the criteria and
      involved 30 immediate, 71 early, 77 one-stage conventional, and 66 two-stage
      conventional subjects. Three immediate loading trials showed an increase in the
      amount of marginal bone loss over time, while the majority of early and
      conventionally loaded implants exhibited a decrease in the amount of bone loss in
      the second year compared with the first 12-month period. Probing depth at 24
      months showed a significant difference between early and conventional loading;
      SMD 0.5 (95% confidence interval 0.03, 0.97). No other statistically significant
      differences were found between either immediate or early and conventional loading
      for any indices. CONCLUSIONS: No deleterious effects up to 24 months have been
      shown from immediate or early loading. Conventional loading after a 3-month
      healing period has not been proven to be the only acceptable protocol for
      mandibular IOD, but further long-term studies are needed to confirm this.

PMID- 17509066
TI  - Regulation and function of maternal mRNA destabilization during early Drosophila
      development.
AB  - Early embryonic development in all animals depends on maternally provided gene
      products. Posttranscriptional and posttranslational processes control spatial and
      temporal readout of the maternal information. This review focuses on the control
      of maternal transcript stability in the early Drosophila embryo and how
      transcript destabilization is necessary for normal development. The molecular
      pathways that regulate transcript stability are often intimately linked with
      other posttranscriptional mechanisms such as mRNA localization and translational
      regulation. These additional mechanisms are explored here with an emphasis on
      their relationship to transcript decay.

PMID- 17509067
TI  - Comparison of the effects of pioglitazone and voglibose on circulating total and
      high-molecular-weight adiponectin, and on two fibrinolysis inhibitors, in
      patients with Type 2 diabetes.
AB  - BACKGROUND: To investigate short-term effects of pioglitazone and voglibose on
      serum concentrations of both total and high-molecular-weight (HMW) adiponectin
      measured with a novel sandwich enzyme-linked immunosorbent assay (ELISA) ,and on
      plasma fibrinolysis indicators, in Type 2 diabetic patients with inadequate
      glycaemic control on sulphonylureas. METHODS: Thirty-four diabetic patients were
      randomized to receive pioglitazone or voglibose treatment for 12 weeks, after
      which serum HMW adiponectin was measured. Plasma plasminogen activator inhibitor
      (PAI) 1 and thrombin-activatable fibrinolysis inhibitor (TAFI), a recently
      identified inhibitor of fibrinolysis, were measured as fibrinolysis inhibitors.
      RESULTS: At baseline, serum HMW adiponectin correlated negatively with plasma
      TAFI in all patients with Type 2 diabetes (r = -0.367, P = 0.0423). Both groups
      showed similar improvements in glycaemic control. Serum total and HMW adiponectin
      increased in patients treated with pioglitazone, but did not change in patients
      treated with voglibose. The HMW : total adiponectin ratio increased significantly
      after treatment with pioglitazone (P = 0.0004). The change in HbA(1c) correlated
      negatively with changes in serum HMW adiponectin in patients treated with
      pioglitazone (r = -0.694, P = 0.0034). Plasma PAI-1 and TAFI did not change with
      pioglitazone treatment. CONCLUSION: Increased serum HMW adiponectin may
      contribute to the improvement in glycaemic control after pioglitazone treatment.
      Plasma PAI-1 and TAFI were unchanged by either drug.

PMID- 17509068
TI  - Effects of structured hospital-based care compared with standard care for Type 2
      diabetes-The Asker and Baerum Cardiovascular Diabetes Study, a randomized trial.
AB  - AIMS: Few studies have compared structured vs. standard care on the effects of
      modifying several cardiovascular (CV) risk factors in subjects with Type 2
      diabetes. Because of the complexity of the disease, we hypothesized that
      structured care with a multi-interventional approach is necessary to effectively
      reach treatment goals and to reduce CV risk. METHODS: An open 2-year parallel
      group study in 120 patients (age 59 +/- 10 years, 31 females) with Type 2
      diabetes (median duration 4 years) was conducted. The patients were randomized to
      standard care (follow-up by their general practitioner) or to structured care at
      a hospital outpatient clinic consisting of an initial 6 months' lifestyle
      programme followed by targeted intensified pharmacological treatment to reach
      prespecified goals for glycaemic, lipid and blood pressure (BP) control. The
      primary outcome was change in the estimated 10-year absolute risk for fatal
      coronary heart disease (CHD). RESULTS: One hundred and six patients completed the
      study. Improvements were greater among patients receiving structured rather than
      standard care for systolic BP, triglycerides, glucose and glycated haemoglobin
      (HbA(1c)) (P < 0.05), as well as for the estimated 10-year CHD-risk (17.9% to
      14.5% vs. 18.3% to 19.6%) and the prevalence of a CHD risk >or= 20% (38% to 22%
      vs. 39% to 45%). Most of the reduction in estimated CHD risk (77%) in the
      structured care group was obtained during the period (6-24 months) with
      intensified pharmacological treatment (P < 0.01). CONCLUSIONS: This study shows
      that 2 years of structured care combining lifestyle and pharmacological
      interventions improved several CV risk factors and reduced the estimated 10-year
      absolute risk for CHD in patients with Type 2 diabetes.

PMID- 17509069
TI  - Comparison between vildagliptin and metformin to sustain reductions in HbA(1c)
      over 1 year in drug-naive patients with Type 2 diabetes.
AB  - AIMS: To evaluate the ability of vildagliptin and metformin to sustain reductions
      in HbA(1c) over a 1-year treatment period in drug-naive patients with Type 2
      diabetes (Type 2 DM). METHODS: Double-blind, randomized, multicentre, active
      controlled, parallel-group study of 52-week treatment with vildagliptin (100 mg
      daily, n = 526) or metformin (titrated to 2000 mg daily, n = 254) in drug-naive
      patients (baseline HbA(1c) = 7.5-11.0%). HbA(1c) was measured periodically over 1
      year. RESULTS: Vildagliptin and metformin each rapidly decreased HbA(1c) from an
      equal baseline of 8.7%. Most of the HbA(1c) reduction was attained by week 12,
      and the efficacy was sustained throughout 1-year treatment with both agents. At
      the study end, significant HbA(1c) reductions from baseline were seen with both
      vildagliptin (-1.0 +/- 0.1%, P < 0.001) and metformin (-1.4 +/- 0.1%, P < 0.001);
      however, statistical non-inferiority of 50 mg vildagliptin twice daily to 1000 mg
      metformin twice daily was not established. Body weight did not change during the
      1-year treatment with vildagliptin (0.3 +/- 0.2 kg, P = 0.17) and decreased in
      metformin-treated patients (-1.9 +/- 0.3 kg, P < 0.001). The proportion of
      patients experiencing an adverse event was 70.1 vs. 75.4% in patients receiving
      vildagliptin and metformin, respectively. The proportion of patients experiencing
      a gastrointestinal adverse event was twofold higher in the metformin group,
      driven by a 3-4-fold greater incidence of diarrhoea, nausea and abdominal pain.
      The incidence of hypoglycaemia was similarly low in both groups (< 1%).
      CONCLUSIONS: A clinically meaningful decrease in HbA(1c) that was sustained
      throughout a 1-year treatment in drug-naive patients with Type 2 DM was seen with
      both metformin and vildagliptin monotherapy.

PMID- 17509070
TI  - The association of life course socio-economic position with diagnosis, treatment,
      control and survival of women with diabetes: findings from the British Women's
      Heart and Health Study.
AB  - OBJECTIVES: To examine the association of socio-economic position (SEP) with the
      diagnosis, treatment and control of diabetes, and with survival in women with and
      without Type 2 diabetes. METHODS: Prospective cohort study of 4277 women from 23
      centres in Great Britain, aged 60-79 years at baseline. RESULTS: Of the 4277
      women, 220 (5.1%) were known to have Type 2 diabetes and a similar number [n =
      188 (4.4%)] had undiagnosed diabetes based on a single fasting glucose level > or
      = 7.0 mmol/l. Neither childhood nor adult SEP was associated with being correctly
      diagnosed amongst the 408 women with either diagnosed or undiagnosed diabetes. In
      both women with and without diabetes, SEP was associated with more adverse levels
      of fasting insulin, triglycerides, high-density lipoprotein cholesterol and body
      mass index, but was not associated with glycated haemoglobin in either group.
      Over the follow-up period, 395 women died. The hazard ratio for all-cause
      mortality per additional indicator of adverse SEP in adulthood in women with
      diabetes [1.40 (1.05, 1.85)] was similar to that in women without diabetes [1.26
      (1.12, 1.41], P for difference in the two estimates = 0.70). Childhood SEP was
      not associated with survival. CONCLUSION/INTERPRETATION: A considerable number of
      older women with Type 2 diabetes are not diagnosed, but SEP is not related to
      being correctly diagnosed. The marked socio-economic gradient for all-cause
      mortality is the same for women with and without diabetes and is not fully
      explained by conventional risk factors.

PMID- 17509071
TI  - Evidence-based medicine for diabetes educators: a pilot study.
AB  - AIMS: Health-care professionals are increasingly asked to communicate research
      results to patients and consumers. Diabetes educators play a decisive role in the
      information process of patients with diabetes. Evidence-based medicine (EBM) is
      not a regular part of their training in Germany. We performed a pilot study to
      test whether the inclusion of a short EBM module into the standard graduate
      programme is feasible and leads to a meaningful increase in knowledge and skills.
      METHODS: The study group consisted of 121 diabetes educator trainees. The EBM
      modules were delivered in 1- to 3-day courses. Increase in knowledge and skills
      were assessed using a questionnaire covering three main elements: (i) general
      aspects of an intervention study, (ii) effect size calculation, (iii) general
      aspects of evidence-based patient information and communicating numbers as
      patient orientated statements. Two researchers independently rated the assessment
      sheets. RESULTS: The majority of participants rated the course as important and
      useful but too short. Knowledge and skills in EBM increased after the course by 2
      points out of 13.5 (mean score before course 5 +/- 2 vs. 7 +/- 2; P < 0.001).
      Inter-rater reliability analysis using Cohen's Kappa coefficients demonstrated
      substantial to almost perfect agreement for 10 of the 13 items. CONCLUSIONS: Our
      pilot study demonstrates that EBM education for diabetes educator trainees is
      feasible. However, the increase in knowledge and skills appears not to be
      clinically relevant. Short EBM courses are unlikely to yield important effects.
      More intensified course formats are necessary to meet the needs of diabetes
      educators.

PMID- 17509072
TI  - Prognostic significance of asymptomatic coronary artery disease in patients with
      diabetes and need for early revascularization therapy.
AB  - AIMS: Information on the clinical outcome of patients with diabetes with silent
      myocardial ischaemia is limited. We compared the clinical and angiographic
      characteristics, and the clinical outcomes of diabetic patients with asymptomatic
      or symptomatic coronary artery disease (CAD). METHODS: Three hundred and ten
      consecutive diabetic patients with CAD were divided into two groups according to
      the presence of angina and followed for a mean of 5 years. Fifty-six asymptomatic
      patients with a positive stress test and CAD on coronary angiography were
      compared with 254 symptomatic patients, 167 with unstable angina and 87 with
      chronic stable angina. RESULTS: Although the severity of coronary atherosclerosis
      was similar in asymptomatic and symptomatic patients, revascularization therapy
      was performed less frequently in the asymptomatic than the symptomatic patients
      (26.8 vs. 62.0%; P < 0.001). Asymptomatic patients experienced a similar number
      of major adverse cardiac events (MACEs; death, non-fatal myocardial infarction,
      and revascularization; 32 vs. 28%; P = 0.57), but had higher cardiac mortality
      than symptomatic patients (26 vs. 9%; P < 0.001). However, patients who underwent
      revascularization therapy at the time of CAD diagnosis in these two groups showed
      similar MACE and cardiac mortality (20.0 vs. 22.5%, 6.7 vs. 5.3%, respectively;
      all P > 0.05). CONCLUSIONS: This study suggests that diabetic patients with
      asymptomatic CAD have a higher cardiac mortality risk than those with symptomatic
      CAD, and that lack of revascularization therapy may be responsible for the poorer
      survival.

PMID- 17509073
TI  - Caffeine restores regional brain activation in acute hypoglycaemia in healthy
      volunteers.
AB  - AIMS: Caffeine enhances counterregulatory responses to acute hypoglycaemia. Our
      aim was to explore its effects on cortical function, which are not known at
      present. METHODS: Regional brain activation during performance of the four-choice
      reaction time (4CRT) at different levels of complexity was measured using
      functional magnetic resonance imaging (fMRI) at euglycaemia (5 mmol/l) and
      hypoglycaemia (2.6 mmol/l) in the presence and absence of caffeine in six healthy
      right-handed men. RESULTS: During hypoglycaemia, caffeine enhanced adrenaline
      responses to hypoglycaemia (2.5 +/- 0.7 nmol/l to 4.0 +/- 1.0 nmol/l, P = 0.01)
      and restored the brain activation response to the non-cued 4CRT, the linear
      increases in regional brain activation associated with increased task complexity
      and the ability to respond to a cue that were lost in hypoglycaemia alone.
      CONCLUSIONS: Caffeine can sustain regional brain activation patterns lost in
      acute hypoglycaemia, with some restoration of cortical function and enhanced
      adrenaline responsiveness. A methodology has been established that may help in
      the development of therapies to protect against severe hypoglycaemia in insulin
      therapy for patients with diabetes and problematic hypoglycaemia.

PMID- 17509074
TI  - A genetic screen identifies mutations in the yeast WAR1 gene, linking
      transcription factor phosphorylation to weak-acid stress adaptation.
AB  - Exposure of the yeast Saccharomyces cerevisiae to weak organic acids such as the
      food preservatives sorbate, benzoate and propionate leads to the pronounced
      induction of the plasma membrane ATP-binding cassette (ABC) transporter, Pdr12p.
      This protein mediates efflux of weak acid anions, which is essential for stress
      adaptation. Recently, we identified War1p as the dedicated transcriptional
      regulator required for PDR12 stress induction. Here, we report the results from a
      genetic screen that led to the isolation of two war1 alleles encoding mutant
      variants, War1-28p and War1-42p, which are unable to support cell growth in the
      presence of sorbate. DNA sequencing revealed that War1-28 encodes a truncated
      form of the transcriptional regulator, and War1-42 carries three clustered
      mutations near the C-terminal activation domain. Although War1-42 is expressed
      and properly localized in the nucleus, the War1-42p variant fails to bind the
      weak-acid-response elements in the PDR12 promoter, as shown by in vivo
      footprinting. Importantly, in contrast with wild-type War1p, War1-42p is also no
      longer phosphorylated upon weak-acid challenge, demonstrating that
      phosphorylation of War1p, its activation and DNA binding are tightly linked
      processes that are essential for adaptation to weak-acid stress.

PMID- 17509075
TI  - Degradation of nuclear DNA by DNase II-like acid DNase in cortical fiber cells of
      mouse eye lens.
AB  - The eye lens is composed of fiber cells that differentiate from epithelial cells
      on its anterior surface. In concert with this differentiation, a set of proteins
      essential for lens function is synthesized, and the cellular organelles are
      degraded. DNase II-like acid DNase, also called DNase IIbeta, is specifically
      expressed in the lens, and degrades the DNA in the lens fiber cells. Here we
      report that DNase II-like acid DNase is synthesized as a precursor with a signal
      sequence, and is localized to lysosomes. DNase II-like acid DNase mRNA was found
      in cortical fiber cells but not epithelial cells, indicating that its expression
      is induced during the differentiation of epithelial cells into fiber cells.
      Immunohistochemical and immunocytochemical analyses indicated that DNase II-like
      acid DNase was colocalized with Lamp-1 in the lysosomes of fiber cells in a
      relatively narrow region bordering the organelle-free zone, and was often found
      in degenerating nuclei. A comparison by microarray analysis of the gene
      expression profiles between epithelial and cortical fiber cells of young mouse
      lens indicated that some genes for lysosomal enzymes (cathepsins and lipases)
      were strongly expressed in the fiber cells. These results suggest that the
      lysosomal system plays a role in the degradation of cellular organelles during
      lens cell differentiation.

PMID- 17509076
TI  - The localization of FGFR3 mutations causing thanatophoric dysplasia type I
      differentially affects phosphorylation, processing and ubiquitylation of the
      receptor.
AB  - Recurrent missense fibroblast growth factor receptor 3 (FGFR3) mutations have
      been ascribed to skeletal dysplasias of variable severity including the lethal
      neonatal thanatophoric dysplasia types I (TDI) and II (TDII). To elucidate the
      role of activating mutations causing TDI on receptor trafficking and endocytosis,
      a series of four mutants located in different domains of the receptor were
      generated and transiently expressed. The putatively elongated X807R receptor was
      identified as three isoforms. The fully glycosylated mature isoform was
      constitutively but mildly phosphorylated. Similarly, mutations affecting the
      extracellular domain (R248C and Y373C) induced moderate constitutive receptor
      phosphorylation. By contrast, the K650M mutation affecting the tyrosine kinase 2
      (TK2) domain produced heavy phosphorylation of the nonglycosylated and mannose
      rich isoforms that impaired receptor trafficking through the Golgi network. This
      resulted in defective expression of the mature isoform at the cell surface.
      Normal processing was rescued by tyrosine kinase inhibitor treatment.
      Internalization of the R248C and Y373C mutant receptors, which form stable
      disulfide-bonded dimers at the cell surface was less efficient than the wild
      type, whereas ubiquitylation was markedly increased but apparently independent of
      the E3 ubiquitin-ligase casitas B-lineage lymphoma (c-Cbl). Constitutive
      phosphorylation of c-Cbl by the K650M mutant appeared to be related to the
      intracellular retention of the receptor. Therefore, although mutation K650M
      affecting the TK2 domain induces defective targeting of the overphosphorylated
      receptor, a different mechanism characterized by receptor retention at the plasma
      membrane, excessive ubiquitylation and reduced degradation results from mutations
      that affect the extracellular domain and the stop codon.

PMID- 17509077
TI  - Tissue factor pathway inhibitor is highly susceptible to chymase-mediated
      proteolysis.
AB  - Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type protease
      inhibitor that primarily inhibits the extrinsic pathway of blood coagulation. It
      is synthesized by various cells and its expression level increases in
      inflammatory environments. Mast cells and neutrophils accumulate at sites of
      inflammation and vascular disease where they release proteinases as well as
      chemical mediators of these conditions. In this study, the interactions between
      TFPI and serine proteinases secreted from human mast cells and neutrophils were
      examined. TFPI inactivated human lung tryptase, and its inhibitory activity was
      stronger than that of antithrombin. In contrast, mast cell chymase rapidly
      cleaved TFPI even at an enzyme to substrate molar ratio of 1:500, resulting in
      markedly decreased TFPI anticoagulant and anti-(factor Xa) activities. N-terminal
      amino-acid sequencing and MS analyses of the proteolytic fragments revealed that
      chymase preferentially cleaved TFPI at Tyr159-Gly160, Phe181-Glu182, Leu89-Gln90,
      and Tyr268-Glu269, in that order, resulting in the separation of the three
      individual Kunitz domains. Neutrophil-derived proteinase 3 also cleaved TFPI, but
      the reaction was much slower than the chymase reaction. In contrast, alpha
      chymotrypsin, which shows similar substrate specificities to those of chymase,
      resulted in a markedly lower level of TFPI degradation. These data indicate that
      TFPI is a novel and highly susceptible substrate of chymase. We propose that
      chymase-mediated proteolysis of TFPI may induce a thrombosis-prone state at
      inflammatory sites.

PMID- 17509078
TI  - Complete reconstitution of an ATP-binding cassette transporter LolCDE complex
      from separately isolated subunits.
AB  - The LolCDE complex of Escherichia coli belongs to the ATP-binding cassette
      transporter superfamily and mediates the detachment of lipoproteins from the
      inner membrane, thereby initiating lipoprotein sorting to the outer membrane. The
      complex is composed of one copy each of membrane subunits LolC and LolE, and two
      copies of ATPase subunit LolD. To establish the conditions for reconstituting the
      LolCDE complex from separately isolated subunits, the ATPase activities of LolD
      and LolCDE were examined under various conditions. We found that both LolD and
      LolCDE were inactivated on incubation at 30 degrees C in a detergent solution.
      ATP and phospholipids protected LolCDE, but not LolD. Furthermore, phospholipids
      reactivated LolCDE even after its near complete inactivation. LolD was also
      protected from inactivation when membrane subunits and phospholipids were present
      together, suggesting the phospholipid-dependent reassembly of LolCDE subunits.
      Indeed, the functional lipoprotein-releasing machinery was reconstituted into
      proteoliposomes with E. coli phospholipids and separately purified LolC, LolD and
      LolE. Preincubation with phospholipids at 30 degrees C was essential for the
      reconstitution of the functional machinery from subunits. Strikingly, the
      lipoprotein-releasing activity was also reconstituted from LolE and LolD without
      LolC, suggesting the intriguing possibility that the minimum lipoprotein
      releasing machinery can be formed from LolD and LolE. We report here the complete
      reconstitution of a functional ATP-binding cassette transporter from separately
      purified subunits.

PMID- 17509079
TI  - Progress for dengue virus diseases. Towards the NS2B-NS3pro inhibition for a
      therapeutic-based approach.
AB  - Transmitted by the Aedes aegypti mosquito, the dengue virus is the etiological
      agent of dengue fever, dengue hemorrhagic fever and dengue shock syndrome, and,
      as such, is a significant factor in the high death rate found in most tropical
      and subtropical areas of the world. Dengue diseases are not only a health burden
      to developing countries, but pose an emerging problem worldwide. The
      immunopathological mechanisms appear to include a complex series of immune
      responses. A rapid increase in the levels of cytokines and chemical mediators
      during dengue disease plays a key role in inducing plasma leakage, shock and
      hemorrhagic manifestations. Currently, there are no vaccines available against
      dengue virus, although several tetravalent live-attenuated dengue vaccines are in
      clinical phases I or II, and prevention through vaccination has become a major
      priority on the agendas of the World Health Organization and of national
      ministries of health and military organizations. An alternative to vaccines is
      found in therapeutic-based approaches. Understanding the molecular mechanisms of
      viral replication has led to the development of potential drugs, and new
      molecular viral targets for therapy are emerging. The NS3 protease domain of the
      NS3 protein is responsible for processing the viral polyprotein and its
      inhibition is one of the principal aims of pharmacological therapy. This review
      is an overview of the progress made against dengue virus; in particular, it
      examines the unique properties--structural and functional--of the NS3 protease
      for the treatment of dengue virus infections by the inhibition of viral
      polyprotein processing.

PMID- 17509080
TI  - Irreversible cross-linking of heme to the distal tryptophan of stromal ascorbate
      peroxidase in response to rapid inactivation by H2O2.
AB  - Ascorbate peroxidase (APX) isoforms localized in the stroma and thylakoid
      membrane of chloroplasts play a central role in scavenging reactive oxygen
      species generated by photosystems. These enzymes are inactivated within minutes
      by H2O2 when the reducing substrate, ascorbate, is depleted. We found that, when
      the enzyme is inactivated by H2O2, a heme at the catalytic site of a stromal APX
      isoform is irreversibly cross-linked to a tryptophan residue facing the distal
      cavity. Mutation of this tryptophan to phenylalanine abolished the cross-linking
      and increased the half-time for inactivation from <10 to 62 s. In contrast with
      H2O2-tolerant peroxidases, rapid formation of the cross-link in APXs suggests
      that a radical in the reaction intermediate tends to be located in the distal
      tryptophan so that heme is easily cross-linked to it. This is the first report of
      a mutation that improves the tolerance of chloroplast APXs to H2O2.

PMID- 17509082
TI  - RNA interference-mediated knock-down of transient receptor potential vanilloid 1
      prevents forepaw inflammatory hyperalgesia in rat.
AB  - Transient receptor potential vanilloid (TRPV)1 is a ligand-gated cation channel
      expressed by primary sensory neurons, including those in the dorsal root ganglia
      (DRG). TRPV1 plays an essential role in development of inflammatory thermal
      hyperalgesia after tissue injury and its expression in rat lumbar DRG is
      increased after hindpaw inflammation. However, the identity of factors mediating
      forepaw inflammatory hyperalgesia has remained elusive. Here, we examined
      behavioral responses to noxious thermal stimuli after forepaw inflammation in
      rats and found that inflammation induced by intraplantar injection of complete
      Freund's adjuvant significantly reduced hot-plate latency (HPL) at 50 degrees C.
      TRPV1 expression levels in the ipsilateral cervical DRG were also elevated after
      forepaw inflammation. By contrast, HPL at 56 degrees C was not shortened after
      forepaw inflammation and expression of TRPV2, a TRPV1 homolog, in the DRG was not
      increased. Paratracheal injection of short interfering RNA targeting TRPV1
      blocked TRPV1 up-regulation in cervical DRG and abolished inflammation-mediated
      HPL reductions seen at 50 degrees C. However, thermal hyperalgesia previously
      established by inflammation was not reversed by short interfering RNA injection.
      These results indicate that: (i) enhanced TRPV1 expression in cervical DRG is
      closely associated with development of inflammatory thermal hyperalgesia in the
      forepaw after tissue injury and (ii) RNA interference targeting TRPV1 prevents
      inflammatory thermal hyperalgesia after forepaw injuries but does not ameliorate
      it when already established in a rat model of nociceptive pain representing upper
      limb injury in humans.

PMID- 17509081
TI  - Cyclosporin A-induced oxidative stress is not the consequence of an increase in
      mitochondrial membrane potential.
AB  - Cyclosporin A induces closure of the mitochondrial permeability transition pore.
      We aimed to investigate whether this closure results in concomitant increases in
      mitochondrial membrane potential (DeltaPsim) and the production of reactive
      oxygen species. Fluorescent probes were used to assess DeltaPsim (JC-1, 5,5',6,6'
      tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl-carbocyanine iodide), reactive
      oxygen species [DCF, 5- (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein
      diacetate, acetyl ester] and [Ca2+][Fluo-3, glycine N-[4-[6-[(acetyloxy)methoxy]
      2,7-dichloro-3-oxo-3H-xanthen-9-yl]-2-[2-[2-[bis[2-[(acetyloxy)methoxy]-2
      oxyethyl]amino]-5-methylphenoxy]ethoxy]phenyl]-N-[2-[(acetyloxy)methoxy]-2
      oxyethyl]-(acetyloxy)methyl ester] in human kidney cells (HK-2 cells) and in a
      line of human small cell carcinoma cells (GLC4 cells), because these do not
      express cyclosporin A-sensitive P-glycoprotein. We used transfected GLC4 cells
      expressing P-glycoprotein as control for GLC4 cells. NIM811 (N-methyl-4
      isoleucine-cyclosporin) and PSC833 (SDZ-PSC833) were applied as selective
      mitochondrial permeability transition pore and P-glycoprotein blockers,
      respectively. To study the effect of cyclosporin A on mitochondrial function, we
      isolated mitochondria from fresh pig livers. Cyclosporin A and PSC833 induced a
      more than two-fold increase in JC-1 fluorescence in HK-2 cells, whereas NIM811
      had no effect. None of the three substances induced a significant increase in JC
      1 fluorescence in GLC4 cells. Despite this, cyclosporin A, NIM811 and PSC833
      induced a 1.5-fold increase in DCF fluorescence (P<0.05) and a two-fold increase
      in Fluo-3 fluorescence (P<0.05). Studies in isolated mitochondria showed that
      blockage of mitochondrial permeability transition pores by cyclosporin A affected
      neither DeltaPsim, ATP synthesis, nor respiration rate. The mitochondrial
      permeability transition pore blockers cyclosporin A and NIM811, but also the non
      mitochondrial permeability transition pore blocker PSC833, induced comparable
      degrees of reactive oxygen species production and cytosolic [Ca2+]. Neither
      mitochondria, effects on P-glycoprotein nor inhibition of calcineurin therefore
      play a role in cyclosporin A-induced oxidative stress and disturbed Ca2+
      homeostasis.

PMID- 17509083
TI  - AMPA and NMDA receptor regulation of firing activity in 5-HT neurons of the
      dorsal and median raphe nuclei.
AB  - The glutamatergic regulation of 5-hydroxytryptamine (5-HT) neuronal activity has
      not been extensively studied. Here, we used extracellular single unit recording
      in midbrain slices to examine glutamate receptor mediated effects on 5-HT
      neuronal activity in the dorsal raphe nucleus (DRN) and the median raphe nucleus
      (MRN). Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 and 3
      microm) concentration-dependently increased firing in 5-HT neurons in both the
      DRN and the MRN. The response to AMPA was blocked by the AMPA receptor
      antagonist, 6,7-dinitroquinoxaline-2,3(1H-4H)-dione (DNQX; 10 microm) but not the
      N-methyl-d-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic
      acid (AP-5; 50 microm). NMDA (10-100 microm) also increased 5-HT neuronal firing
      in a concentration-dependent manner in both the DRN and MRN; a response that was
      blocked by AP-5 (50 microm). In some DRN neurons the NMDA response was partially
      antagonized by DNQX (10 microm) suggesting that NMDA, as well as directly
      activating 5-HT neurons, evokes local release of glutamate, which indirectly
      activates AMPA receptors on 5-HT neurons. Responses of DRN 5-HT neurons to AMPA
      and NMDA were enhanced by the gamma-amino-butyric acid (GABA)(A) receptor
      antagonist, bicuculline (50 microm), suggesting that both AMPA and NMDA increase
      local release of GABA. Finally in the DRN the 5-HT(1A) receptor antagonist,
      WAY100635 (100 nm), failed to enhance the response of 5-HT neurons to AMPA and
      caused only a small increase in the excitatory response to NMDA suggesting a low
      degree of tonic activation of 5-HT(1A) autoreceptors even when 5-HT neuronal
      firing rate is high.

PMID- 17509084
TI  - 5-HT(1B) receptors in nucleus accumbens efferents enhance both rewarding and
      aversive effects of cocaine.
AB  - Whether serotonin-1B (5-HT(1B)) receptor activation enhances or diminishes the
      reinforcing properties of psychostimulants remains unclear. We have previously
      shown that increased expression of 5-HT(1B) receptors in nucleus accumbens (NAcc)
      shell neurons sensitized rats to the locomotor-stimulating and rewarding
      properties of cocaine. In this study we further examined the contribution of 5
      HT(1B) receptors on the effect of cocaine under conditions intended to
      selectively influence either conditioned place preference or avoidance (CPP or
      CPA, respectively). Viral-mediated gene transfer techniques were used to
      overexpress 5-HT(1B) receptors in medial NAcc shell medium spiny neurons
      projecting to the ventral tegmental area. Animals were then conditioned to
      associate place cues with the effects of either a low (5 mg/kg) or moderately
      high (20 mg/kg) dosage of cocaine immediately or 45 min after intraperitoneal
      cocaine administration. Animals with increased 5-HT(1B) expression showed cocaine
      induced CPP immediately after administration of the low 5 mg/kg dose of cocaine,
      but a CPA 45 min after administration of the high 20 mg/kg dose. Control animals
      showed no preference at the 5 mg/kg dose and a significant preference at 20
      mg/kg. Given this, we believe that increased 5-HT(1B) receptor activation in NAcc
      shell projection neurons intensifies both the rewarding and negative properties
      of cocaine use.

PMID- 17509085
TI  - Similar GABAergic inputs in dentate granule cells born during embryonic and adult
      neurogenesis.
AB  - Neurogenesis in the dentate gyrus of the hippocampus follows a unique temporal
      pattern that begins during embryonic development, peaks during the early
      postnatal stages and persists through adult life. We have recently shown that
      dentate granule cells born in early postnatal and adult mice acquire a remarkably
      similar afferent connectivity and firing behavior, suggesting that they
      constitute a homogeneous functional population [Laplagne et al. (2006)PLoS Biol.,
      4, e409]. Here we extend our previous study by comparing mature neurons born in
      the embryonic and adult hippocampus, with a focus on intrinsic membrane
      properties and gamma-aminobutyric acid (GABA)ergic synaptic inputs. For this
      purpose, dividing neuroblasts of the ventricular wall were retrovirally labeled
      with green fluorescent protein at embryonic day 15 (E15), and progenitor cells of
      the subgranular zone were labeled with red fluorescent protein in the same mice
      at postnatal day 42 (P42, adulthood). Electrophysiological properties of mature
      neurons born at either stage were then compared in the same brain slices. Evoked
      and spontaneous GABAergic postsynaptic responses of perisomatic and dendritic
      origin displayed similar characteristics in both neuronal populations. Miniature
      GABAergic inputs also showed similar functional properties and pharmacological
      profile. A comparative analysis of the present data with our previous
      observations rendered no significant differences among GABAergic inputs recorded
      from neurons born in the embryonic, early postnatal and adult mice. Yet, embryo
      born neurons showed a reduced membrane excitability, suggesting a lower
      engagement in network activity. Our results demonstrate that granule cells of
      different age, location and degree of excitability receive GABAergic inputs of
      equivalent functional characteristics.

PMID- 17509086
TI  - Indole-3-acetic acid in microbial and microorganism-plant signaling.
AB  - Diverse bacterial species possess the ability to produce the auxin phytohormone
      indole-3-acetic acid (IAA). Different biosynthesis pathways have been identified
      and redundancy for IAA biosynthesis is widespread among plant-associated
      bacteria. Interactions between IAA-producing bacteria and plants lead to diverse
      outcomes on the plant side, varying from pathogenesis to phyto-stimulation.
      Reviewing the role of bacterial IAA in different microorganism-plant interactions
      highlights the fact that bacteria use this phytohormone to interact with plants
      as part of their colonization strategy, including phyto-stimulation and
      circumvention of basal plant defense mechanisms. Moreover, several recent reports
      indicate that IAA can also be a signaling molecule in bacteria and therefore can
      have a direct effect on bacterial physiology. This review discusses past and
      recent data, and emerging views on IAA, a well-known phytohormone, as a microbial
      metabolic and signaling molecule.

PMID- 17509087
TI  - Roles of extracellular signal-regulated protein kinases 5 in spinal microglia and
      primary sensory neurons for neuropathic pain.
AB  - Neuropathic pain that occurs after peripheral nerve injury is poorly controlled
      by current therapies. Increasing evidence shows that mitogen-activated protein
      kinase (MAPK) play an important role in the induction and maintenance of
      neuropathic pain. Here we show that activation of extracellular signal-regulated
      protein kinases 5 (ERK5), also known as big MAPK1, participates in pain
      hypersensitivity caused by nerve injury. Nerve injury increased ERK5
      phosphorylation in spinal microglia and in both damaged and undamaged dorsal root
      ganglion (DRG) neurons. Antisense knockdown of ERK5 suppressed nerve injury
      induced neuropathic pain and decreased microglial activation. Furthermore,
      inhibition of ERK5 blocked the induction of transient receptor potential channels
      and brain-derived neurotrophic factor expression in DRG neurons. Our results show
      that ERK5 activated in spinal microglia and DRG neurons contributes to the
      development of neuropathic pain. Thus, blocking ERK5 signaling in the spinal cord
      and primary afferents has potential for preventing pain after nerve damage.

PMID- 17509088
TI  - The chemokine stromal cell-derived factor-1/CXCL12 activates the nigrostriatal
      dopamine system.
AB  - We recently demonstrated that dopaminergic (DA) neurons of the rat substantia
      nigra constitutively expressed CXCR4, receptor for the chemokine stromal cell
      derived factor-1 (SDF-1)/CXCL12 (SDF-1). To check the physiological relevance of
      such anatomical observation, in vitro and in vivo approaches were used. Patch
      clamp recording of DA neurons in rat substantia nigra slices revealed that SDF-1
      (10 nmol/L) induced: (i) a depolarization and increased action potential
      frequency; and (ii) switched the firing pattern of depolarized DA neurons from a
      tonic to a burst firing mode. This suggests that SDF-1 could increase DA release
      from neurons. Consistent with this hypothesis, unilateral intranigral injection
      of SDF-1 (50 ng) in freely moving rat decreased DA content and increased
      extracellular concentrations of DA and metabolites in the ipsilateral dorsal
      striatum, as shown using microdialysis. Furthermore, intranigral SDF-1 injection
      induced a contralateral circling behavior. These effects of SDF-1 were mediated
      via CXCR4 as they were abrogated by administration of a selective CXCR4
      antagonist. Altogether, these data demonstrate that SDF-1, via CXCR4, activates
      nigrostriatal DA transmission. They show that the central functions of chemokines
      are not restricted, as originally thought, to neuroinflammation, but extend to
      neuromodulatory actions on well-defined neuronal circuits in non-pathological
      conditions.

PMID- 17509089
TI  - Brush cells in the human duodenojejunal junction: an ultrastructural study.
AB  - Brush cells have been identified in the respiratory and gastrointestinal tract
      mucosa of many mammalian species. In humans they are found in the respiratory
      tract and the gastrointestinal apparatus, in both the stomach and the
      gallbladder. The function of brush cells is unknown, and most morphological data
      have been obtained in rodents. To extend our knowledge of human brush cells, we
      performed an ultrastructural investigation of human small intestine brush cells.
      Six brush cells identified in five out of more than 300 small intestine biopsies
      performed for gastrointestinal tract disorders were examined by transmission
      electron microscopy. Five brush cells were located on the surface epithelium and
      one in a crypt. The five surface brush cells were characterized by a narrow
      apical pole from which emerged microvilli that were longer and thicker than those
      of enterocytes. The filamentous core extended far into the cell body without
      forming the terminal web. Caveolae were abundant. Filaments were in the form of
      microfilaments and intermediate filaments. Cytoplasmic projections containing
      filaments were found on the basolateral surface of brush cells. In a single cell,
      axons containing vesicles and dense core granules were in close contact both with
      the basal and the lateral surface of the cell. The crypt brush cell appeared less
      mature. We concluded that human small intestine brush cells share a similar
      ultrastructural biology with those of other mammals. They are polarized and well
      differentiated cells endowed with a distinctive cytoskeleton. The observation of
      nerve fibres closely associated with brush cells, never previously described in
      humans, lends support to the hypothesis of a receptor role for these cells.

PMID- 17509090
TI  - Java project on periodontal diseases: a study on transmission of Porphyromonas
      gingivalis in a remote Indonesian population.
AB  - AIM: To study transmission of Porphyromonas gingivalis in a population living in
      a remote area in Southern Java, Indonesia. MATERIAL AND METHODS: Subgingival
      plaque samples from 167 subjects with varying degrees of periodontal breakdown
      were obtained and cultured for the presence of P. gingivalis. After extraction
      and purification of bacterial DNA, amplified fragment length polymorphism
      technique was applied to genotype the bacterial isolates. Computer-assisted
      analysis of the bacterial DNA profiles was used to study distribution of P.
      gingivalis genotypes within family units. RESULTS: One hundred and five of the
      167 (63%) subjects were culture positive for P. gingivalis. In total, 371 P.
      gingivalis isolates were obtained from the 105 subjects. Of the 105 subjects, 30
      were siblings representing 13 families. In six of the 13 families (46%),
      identical P. gingivalis genotypes were found among siblings. In the study group
      of 105 subjects, 13 married couples were identified of which both spouses were
      culture positive for P. gingivalis. None of the 13 couples shared an identical P.
      gingivalis genotype. Twenty P. gingivalis-positive subjects had spouses that were
      culture negative for P. gingivalis. CONCLUSIONS: In this study population,
      vertical transmission of P. gingivalis has occurred within family units, most
      likely from parents to children. Transmission of P. gingivalis between spouses
      could not be established.

PMID- 17509091
TI  - Are there common human leucocyte antigen associations in juvenile idiopathic
      arthritis and periodontitis?
AB  - AIM: The aim of this study was to evaluate common human leucocyte antigen (HLA)
      associations in patients with juvenile idiopathic arthritis (N=110), in patients
      with generalized aggressive periodontitis (N=50) and in patients with chronic
      periodontitis (N=102) in comparison to healthy controls (no periodontitis, no
      arthritis N=102). MATERIAL AND METHODS: HLA-class I and II markers were
      determined using microlymphocytotoxicity test and polymerase chain reaction with
      sequence specific primers. Statistical analyses were carried out by chi(2)-test
      and Yates' correction. If n<5 Fisher's exact test was performed. In the arthritis
      group the influence of HLA on attachment loss was determined by using backwards
      logistic regression considering age, gender, smoking, plaque level, and the
      duration of the disease. RESULTS: In comparison with the controls HLA-DRB3(*)
      occurred more frequently in both females suffering from juvenile idiopathic
      arthritis (74.58%versus 54.54%, p=0.024) and females suffering from chronic
      periodontitis (73.02%versus 54.54%, p=0.035). Furthermore, among patients with
      juvenile idiopathic arthritis an increased odds ratio (OR) for attachment loss
      was found in subjects who expressed HLA-A(*)01 (OR=4.6, p=0.014) or HLA
      A(*)01:DRB3(*) (OR=4.3, p=0.031). CONCLUSION: HLA-DRB3(*) could be a common
      putative risk indicator for juvenile idiopathic arthritis and chronic
      periodontitis among females.

PMID- 17509092
TI  - Effects of enamel matrix derivative and transforming growth factor-beta1 on human
      periodontal ligament fibroblasts.
AB  - AIM: The objective of this study was to evaluate the effects of enamel matrix
      derivative (EMD), transforming growth factor-beta1 (TGF-beta1), and a combination
      of both factors (EMD+TGF-beta1) on periodontal ligament (PDL) fibroblasts.
      MATERIAL AND METHODS: Human PDL fibroblasts were obtained from three adult
      patients with a clinically healthy periodontium, using the explant technique. The
      effects of EMD, TGF-beta1, or a combination of both were analysed on PDL cell
      proliferation, adhesion, wound healing, and total protein synthesis, and on
      alkaline phosphatase (ALP) activity and bone-like nodule formation. RESULTS:
      Treatment with EMD for 4, 7, and 10 days increased cell proliferation
      significantly compared with the negative control (p<0.05). At day 10, EMD and
      EMD+TGF-beta1 showed a higher cell proliferation compared with TGF-beta1
      (p<0.01). Cell adhesion was significantly up-regulated by TGF-beta1 compared with
      EMD and EMD+TGF-beta1 (p<0.01). EMD enhanced in vitro wound healing of PDL cells
      compared with the other treatments. Total protein synthesis was significantly
      increased in PDL cells cultured with EMD compared with PDL cells treated with TGF
      beta1 or EMD+TGF-beta1 (p<0.05). EMD induced ALP activity in PDL fibroblasts,
      which was associated with an increase of bone-like nodules. CONCLUSION: These
      findings support the hypothesis that EMD and TGF-beta1 may play an important role
      in periodontal regeneration. EMD induced PDL fibroblast proliferation and
      migration, total protein synthesis, ALP activity, and mineralization, while TGF
      beta1 increased cellular adhesion. However, the combination of both factors did
      not positively alter PDL fibroblast behaviour.

PMID- 17509093
TI  - Smoking interferes with the prognosis of dental implant treatment: a systematic
      review and meta-analysis.
AB  - AIM: This systematic literature review was performed to investigate if smoking
      interferes with the prognosis of implants with and without accompanying
      augmentation procedures compared with non-smokers. METHODS: A systematic
      electronic and handsearch (articles published between 1989 and 2005; English and
      German language; search terms "dental or oral implants and smoking"; "dental or
      oral implants and tobacco") was performed to identify publications providing
      numbers of failed implants, related to the numbers of smokers and non-smokers for
      meta-analysis. Publications providing statistically examined data of implant
      failures or biologic complications among smokers compared with non-smokers were
      included for systematic review. RESULTS: Of 139 publications identified, 29 were
      considered for meta-analysis and 35 for systematic review. Meta-analysis revealed
      a significantly enhanced risk for implant failure among smokers [implant-related
      odds ratio (OR) 2.25, confidence interval (CI(95%)) 1.96-2.59; patient-related OR
      2.64; CI(95%) 1.70-4.09] compared with non-smokers, and for smokers receiving
      implants with accompanying augmentation procedures (OR 3.61; CI(95%) 2.26-5.77,
      implant related). The systematic review indicated significantly enhanced risks of
      biologic complications among smokers. Five studies revealed no significant impact
      of smoking on prognosis of implants with particle-blasted, acid-etched or anodic
      oxidized surfaces. CONCLUSION: Smoking is a significant risk factor for dental
      implant therapy and augmentation procedures accompanying implantations.

PMID- 17509094
TI  - Systematic review: the application of molecular pathogenesis to prevention and
      treatment of oesophageal adenocarcinoma.
AB  - BACKGROUND: Oesophageal adenocarcinoma is an increasingly common cancer with a
      poor prognosis. It develops in a stepwise progression from Barrett's metaplasia
      to dysplasia, and then adenocarcinoma followed by metastasis. AIM: To outline the
      key molecular changes in oesophageal adenocarcinoma and to summarize the
      chemopreventative and therapeutic strategies proposed. METHODS: A literature
      search was performed to identify appropriate research papers in the field. Search
      terms included: Barrett's (o)esophagus, intestinal metaplasia, (o)esophageal
      adenocarcinoma, molecular changes, genetic changes, pathogenesis,
      chemoprevention, therapeutic strategies and treatment. The search was restricted
      to English language articles. RESULTS: A large number of molecular changes have
      been identified in the progression from Barrett's oesophagus to oesophageal
      adenocarcinoma although there does not appear to be an obligate order of events.
      Potential chemoprevention strategies include acid suppression, anti-inflammatory
      agents and antioxidants. In established adenocarcinoma, targeted treatments under
      evaluation include receptor tyrosine kinase inhibitors of EGFR and cyclin
      dependent kinase inhibitors, which may benefit a subgroup of patients.
      CONCLUSIONS: Advances in molecular methodology have led to a greater
      understanding of the oesophageal adenocarcinoma pathways, which provides
      opportunities for chemoprevention and therapeutic strategies with a mechanistic
      basis. More work is required to assess both the safety and efficacy of these new
      treatments.

PMID- 17509095
TI  - Review article: the role of antibiotics vs. conventional pharmacotherapy in
      treating symptoms of irritable bowel syndrome.
AB  - BACKGROUND: The concept of augmenting the management of irritable bowel syndrome
      with antibiotics is evolving, and many questions remain regarding this therapy
      relative to known and hypothesized irritable bowel syndrome pathophysiology. The
      clinical evidence of small intestinal bacterial overgrowth as an important
      aetiology of irritable bowel syndrome continues to accumulate. Clinical symptoms
      of bacterial overgrowth and irritable bowel syndrome are similar; however, a
      definitive cause-and-effect relationship remains unproven. It is unclear whether
      motility dysfunction causes bacterial overgrowth or gas products of enteric
      bacteria affect intestinal motility in irritable bowel syndrome. AIM: To
      discusses the efficacy and tolerability of current symptom-directed
      pharmacotherapies and of antibiotics in the treatment of irritable bowel
      syndrome. METHODS: A computerized search of PubMed was performed with search
      terms "IBS", "pharmacotherapy" and "antibiotics". Relevant articles were
      selected, and the reference list of selected articles was reviewed to identify
      additional references. RESULTS: Antibiotic treatment benefits a subset of
      irritable bowel syndrome patients. The non-absorbed antibiotic rifaximin has a
      favourable safety and tolerability profile compared with systemic antibiotics and
      demonstrates a therapeutic efficacy comparable with symptom-based irritable bowel
      syndrome pharmacotherapies. CONCLUSION: Rifaximin is the only antibiotic with
      demonstrated sustained benefit beyond therapy cessation in irritable bowel
      syndrome patients in a placebo-controlled trial. Whether antibiotics can improve
      quality of life in patients with irritable bowel syndrome warrants further
      research.

PMID- 17509096
TI  - Disease progression in Chinese chronic hepatitis C patients with persistently
      normal alanine aminotransaminase levels.
AB  - BACKGROUND: Although chronic hepatitis C virus-infected patients with
      persistently normal alanine aminotransaminase levels usually have mild liver
      disease, disease progression can still occur. However, it is uncertain which
      group of patients is at risk of disease progression. AIM: To examine the severity
      of liver disease on liver biopsy in Chinese patients with persistently normal
      alanine aminotransaminase levels, and their disease progression over time.
      METHODS: Eighty-two patients with persistently normal alanine aminotransaminase
      levels were followed up longitudinally. The median time of follow-up was 8.1
      years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. RESULTS:
      At the time of analysis, six of the 82 patients (7.3%) developed decompensated
      liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%)
      vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42
      (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On
      multivariate analysis, initial fibrosis stage F2 or F3 was independently
      associated with progression to decompensated liver cirrhosis (relative risk 2.3,
      95% confidence interval 0.03-2.5, P = 0.02). CONCLUSION: Chinese chronic
      hepatitis C virus patients with persistently normal alanine aminotransaminase
      levels with moderate to severe fibrosis at initial evaluation are more likely to
      develop decompensated liver cirrhosis.

PMID- 17509097
TI  - Incidence and characterization of serum transaminases elevations in pegylated
      interferon and ribavirin treated patients with chronic hepatitis C.
AB  - BACKGROUND: A virological response to pegylated-interferon and ribavirin is
      typically associated with a prompt fall in serum transaminases. For some
      patients, transaminases rise during treatment. AIM: To assess the frequency and
      define factors associated with elevations of serum transaminases. METHODS: A
      total of 169 treated patients were studied. Transaminase elevations were graded
      by WHO criteria - grade 0: no value > baseline, grade 1: 1-2x baseline, grade 2:
      2.1-5x baseline, grade 3: >5x, grade 4: any rise with evidence of liver failure.
      Results 60/169 (35%) patients experienced transaminase elevations: 52 grade 1, 6
      grade 2, 1 grade 3, 1 grade 4. Overall, end of treatment response and sustained
      virological response rates were 72% and 55%. Lower rates were observed in the
      grade 1 elevation group (63% and 40%) compared with patients with grade 0 (79%
      and 65%) and grade > or =2 elevations (85% and 71%). Grade 1 elevations tended to
      occur earlier during treatment than grade > or =2 elevations. Transaminase
      elevations were associated with greater pre-treatment body weight (P = 0.006),
      steatosis (P = 0.008) and poorer sustained virological response rates (P =
      0.007). CONCLUSIONS: Transaminase elevations during treatment of chronic
      Hepatitis C virus with pegylated interferon and ribavirin are common but rarely
      severe. Mild rises may reflect ongoing viral activity in treatment non
      responders. More significant rises are frequently observed despite a virological
      response, and may be because of an immuno-modulating effect of interferon in
      susceptible patients.

PMID- 17509098
TI  - Distinct roles of free leptin, bound leptin and soluble leptin receptor during
      the metabolic-inflammatory response in patients with liver cirrhosis.
AB  - BACKGROUND: Alteration of the leptin system appears to play a role in the
      inflammatory-metabolic response in catabolic diseases such as chronic liver
      diseases. AIM: To investigate the association between leptin components,
      inflammatory markers and hepatic energy and substrate metabolism. METHODS: We
      investigated in vivo hepatic substrate and leptin metabolism in 40 patients
      employing a combination of arterial and hepatic vein catheterization techniques
      and hepatic blood flow measurements. In addition to metabolic, inflammatory and
      neuroendocrine parameters, circulating levels of free leptin, bound leptin and
      soluble leptin receptor were determined. RESULTS: Compared with controls, bound
      leptin and soluble leptin receptor levels were significantly elevated in
      cirrhosis, while free leptin did not increase. In cirrhosis bound leptin was
      correlated with soluble leptin receptor (r = 0.70, P < 0.001). Free leptin was
      positively correlated with metabolic parameters such as energy storage (body fat
      mass; r = 0.36, P < 0.05), insulin and insulin resistance (r = 0.48; r = 0.46, P
      < 0.01) as well as with hepatic glucose and energy release (r = 0.35 and r =
      0.40, P < 0.05). In contrast, bound leptin and soluble leptin receptor were
      linked to proinflammatory cytokines and sympathetic activity (r = 0.61 and r =
      0.56, P < 0.01). CONCLUSION: The components of the leptin system (free leptin,
      bound leptin and soluble leptin receptor) have distinct roles in metabolic and
      inflammatory processes in patients with liver cirrhosis. The better understanding
      of this metabolic and inflammatory tissue-repair response may lead to innovative
      new therapeutic strategies in liver disease as well as in various other catabolic
      diseases.

PMID- 17509099
TI  - Controlled study using wireless capsule endoscopy for the evaluation of the small
      intestine in chronic refractory pouchitis.
AB  - BACKGROUND: Pouchitis is a common long-term complication after ileal pouch anal
      anastomosis for ulcerative colitis. Chronic refractory pouchitis is a treatment
      resistant condition that affects 5-15% of patients. AIM: To test the hypothesis
      of a small bowel involvement using wireless capsule endoscopy. MATERIAL AND
      METHODS: This is a single-blind, prospective, cohort study. Twenty-four patients:
      16 were patients with chronic refractory pouchitis and eight, with a
      macroscopically and histologically normal ileal pouch, were considered as control
      subjects. Diagnosis of pouchitis was confirmed using the pouchitis disease
      activity index. All subjects were submitted to wireless capsule endoscopy
      procedure. Within 2 weeks before wireless capsule endoscopy, patients underwent a
      pouch endoscopy and a small bowel follow-through. Re-examination of the colonic
      surgical and histological specimens was also performed. RESULTS: One patient with
      chronic pouchitis was excluded because of incomplete bowel cleaning. At small
      bowel follow-through of 16 patients, two subjects (13%) showed only a focal
      ectasia of the middle ileum and a substenosis of the pouch. At wireless capsule
      endoscopy all the 15 evaluable patients with chronic pouchitis (100%) showed
      diffuse lesions from duodenum to ileum consisting of aphthae, erosions, erythema,
      atrophy, cobblestone, deep/fissural ulcers. CONCLUSIONS: This enteropathy needs
      further research, and wireless capsule endoscopy could be useful to show
      involvement of small bowel in patients with chronic pouchitis.

PMID- 17509100
TI  - A population-based study of coeliac disease, neurodegenerative and
      neuroinflammatory diseases.
AB  - BACKGROUND: It has been suggested that coeliac disease (CD) is associated with
      several neurological diseases. However, the evidence of such an association is
      inconclusive as earlier research has often been based on small numbers with
      retrospective data collection. AIM: To use Cox regression to examine the risk of
      neurological disease in individuals with CD. METHODS: Through Swedish national
      registers we identified some 14 000 individuals with a diagnosis of CD (1964
      2003) and 70 000 reference individuals matched for age, sex, calendar year and
      county. RESULTS: Coeliac disease was associated with later polyneuropathy [hazard
      ratio (HR) = 3.4; 95% CI = 2.3-5.1]. We found no statistically significant
      association between CD and subsequent multiple sclerosis (HR = 0.9; 95% CI = 0.3
      2.3), Parkinson's disease (HR = 1.2; 95% CI = 0.8-1.9), Alzheimer's disease (HR =
      1.5; 95% CI = 0.9-2.6), hereditary ataxia (HR = 1.3; 95% CI = 0.5-3.6), the
      symptom ataxia (HR = 1.9; 95% CI = 0.6-6.2), Huntington's disease (HR = 1.7; 95%
      CI = 0.3-8.6), myasthenia gravis (HR = 0.8; 95% CI = 0.2-3.8) or spinal muscular
      atrophy (HR = 0.5; 95% CI = 0.1-3.8). Prior polyneuropathy was associated with
      subsequent CD (odds ratio = 5.4; 95% CI = 3.6-8.2). CONCLUSIONS: The association
      between CD and polyneuropathy indicates shared risks. We suggest that individuals
      with polyneuropathy routinely undergo screening for CD. There is no notable
      association between CD and other neurological outcomes investigated in this
      study.

PMID- 17509101
TI  - Irritable bowel syndrome: patients' attitudes, concerns and level of knowledge.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder that
      reduces patients' quality-of-life. Although highly prevalent, little is known
      about patients' understanding of this disorder. AIM: To evaluate the knowledge,
      fears and concerns of IBS patients. METHODS: Seven hundred thirty-six IBS
      patients (Rome II criteria) were eligible for inclusion in this prospective
      study. Each patient received a validated questionnaire to evaluate knowledge,
      attitudes and fears regarding IBS. RESULTS: A total of 261 of 664 potential
      respondents completed the questionnaire (39.3%). 83% of respondents were women,
      with a mean age of 53.7 years, and mean duration of symptoms of 14.2 years.
      Patients frequently believed that IBS develops because of anxiety (80.5%),
      dietary factors (75.1%) and depression (63.2%). Few respondents (28.7%)
      recognized that abdominal pain is the cardinal symptom of IBS, and 40.6% stated
      that colonoscopy can diagnose IBS. One in seven patients stated that IBS turns
      into cancer, and 29.9% noted that IBS increases the risk of inflammatory bowel
      disease. CONCLUSIONS: Many IBS patients have significant misconceptions regarding
      the nature of their disease and its prognosis. An overwhelming majority of IBS
      patients believe that anxiety, dietary factors and depression cause IBS. These
      findings are discordant with physicians' views and practices and highlight the
      need for patient-oriented educational programs.

PMID- 17509102
TI  - Influence of genetics on irritable bowel syndrome, gastro-oesophageal reflux and
      dyspepsia: a twin study.
AB  - BACKGROUND: A genetic contribution has been proposed for irritable bowel syndrome
      (IBS) and gastro-oesophageal reflux disease (GERD), but is controversial. No twin
      data exist for dyspepsia. AIM: To determine the relative contribution of genetic
      factors in GERD, dyspepsia (upper abdominal pain) and IBS. METHODS: A total of
      986 twin pairs (from initial mail-out response 51%). Both members completed
      validated symptom and psychological questionnaires; 481 monozygotic pairs [mean
      (s.d.) age 53 +/- 5.8 years] and 505 dizygotic pairs (mean age 54 +/- 5.6 years).
      RESULTS: Prevalence of IBS, dyspepsia and GERD was 12%, 10% and 20%,
      respectively. Polychoric correlation for monozygotic twins for IBS (0.47) and
      GERD (0.44) were both substantially larger than those for dizygotic twins (0.17
      and -0.37, respectively). Polychoric correlation was slightly lower in
      monozygotic than dizygotic twins for dyspepsia. Genetic modelling confirmed the
      independent additive genetic effects in GERD and IBS but not dyspepsia. Estimates
      of genetic variance were 22% for IBS, 13% for GERD and 0% for dyspepsia, but
      adjusting for anxiety and depression removed the statistical significance for IBS
      and GERD. CONCLUSIONS: There is a genetic contribution to GERD and IBS but not
      dyspepsia; this may be mediated by the hereditability of anxiety and depression.

PMID- 17509103
TI  - Lubiprostone, a locally acting chloride channel activator, in adult patients with
      chronic constipation: a double-blind, placebo-controlled, dose-ranging study to
      evaluate efficacy and safety.
AB  - BACKGROUND: Lubiprostone, a locally acting type-2 chloride channel activator,
      induces intestinal fluid secretion. AIM: To assess efficacy and safety of oral
      lubiprostone at multiple doses for the treatment of chronic constipation.
      METHODS: A total of 129 patients with chronic constipation were randomized to
      receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous
      bowel movement (SBM) frequency, rescue medication use, symptom assessments and
      adverse events (AEs) were tracked. RESULTS: Over the double-blinded period, mean
      SBM frequencies were higher for lubiprostone groups (5.1-6.1) vs. placebo (3.8)
      and the overall difference was statistically significant (P = 0.046). SBM
      frequencies at week 1 were significantly higher in patients taking lubiprostone
      48 or 72 mcg/day (P < or = 0.003) and, at week 2, all three lubiprostone doses
      yielded significantly higher SBM rates vs. placebo (P < or = 0.020).
      Significantly larger proportions of patients taking lubiprostone 48 and 72
      mcg/day also experienced a SBM on the first treatment day (P < or = 0.009). The
      most common AEs were nausea, headache and diarrhoea. CONCLUSIONS: Lubiprostone
      improved SBM rates in a dose-dependent manner. AEs were tolerable for most
      patients. Increased AE severity at 72 mcg/day did not provide a clear risk-to
      benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for
      subsequent Phase 3 studies.

PMID- 17509104
TI  - Pulse cyclophosphamide in steroid-resistant inflammatory bowel disease.

PMID- 17509106
TI  - Neurotoxicity upon infusion of dimethylsulfoxide-cryopreserved peripheral blood
      stem cells in patients with and without pre-existing cerebral disease.
AB  - OBJECTIVE: Toxicity related to the infusion of dimethylsulfoxide (DMSO)
      cryopreserved peripheral blood stem cells (DMSO-PBSC) mainly comprises
      cardiovascular events. Fatal neurotoxicity has been reported in a few cases. DMSO
      represents the putative causative agent of such rare toxicities and elaborate
      strategies to replace DMSO would benefit from the identification of predisposing
      factors for DMSO-related toxicities. METHODS: Here, we report on DMSO-related
      neurotoxicity in a series of patients (n = 51) receiving DMSO-PBSC. The analyzed
      patient-series included eight patients with pre-existing cerebral disease,
      partially with a history of epileptic seizures. RESULTS: Neurotoxicity was
      observed in only one patient who suffered from a generalized tonic seizure upon
      infusion of DMSO-PBSC and for which the clinical course is reported herein. No
      neurotoxicity was observed in the group of patients with pre-existing
      neurological disease. Furthermore, no neurotoxicity was observed in patients who
      received particularly large volumes of DMSO. In all patients, mild non
      neurological side effects occurred but besides the reported seizure no other
      severe adverse events were observed upon PBSC-infusion. CONCLUSIONS: To our
      knowledge, this is the first report addressing the identification of predisposing
      factors for DMSO-related neurotoxicty. We conclude that infusion of DMSO-PBSC can
      be performed safely in patients with pre-existing cerebral disease despite the
      rare occurrence of severe neurotoxicity. Retrospective multicenter studies are
      warranted to identify patients who would benefit from elaborate methods of DMSO
      replacement.

PMID- 17509107
TI  - Acute myeloid leukaemia secondary to treatment with capecitabine for metastatic
      colorectal cancer.
AB  - A 63-year-old woman was diagnosed with acute myelo-monocytic leukaemia,
      associated with MLL gene rearrangement, 16 months after completion of oral
      capecitabine for metastatic colon cancer. Capecitabine, recommended for use in
      metastatic breast and colon cancer and more recently as adjuvant treatment of
      colon cancer, has not previously been reported to be associated with secondary
      cancer.

PMID- 17509108
TI  - Isolated granulocytic sarcoma involving the mediastinum and bilateral cervical
      lymph nodes.

PMID- 17509109
TI  - Cafe au lait macules and juvenile polyps.
AB  - Several hereditary and nonhereditary gastrointestinal tract polyposis syndromes
      exhibit extra-intestinal manifestations, including cutaneous findings. However, a
      lack of information exists regarding cutaneous features of juvenile polyposis.
      Our objective was to document the prevalence of cutaneous hyperpigmented lesions
      in children with juvenile polyposis coli or juvenile polyposis coli and their
      first degree relatives.Children seen in the gastroenterology practice at The
      Children's Hospital in Denver, Colorado with polyps (juvenile polyposis coli,
      sporadic juvenile polyps, and familial adenomatous polyposis coli) and their
      first degree relatives were invited to participate in the study. A comprehensive
      skin examination was performed on those who consented to participate. We found
      that 8 of 14 patients (eight with juvenile polyposis coli, four with juvenile
      polyposis, and two with familial adenomatous polyposis coli) had at least one
      cafe-au-lait macule, compared with three of 27 relatives (p=0.003).The prevalence
      of at least one cafe-au-lait macule in our patients (8/14 or 57.1%, CI: 28.9
      82.3%) was significantly higher than the general population prevalence of 28.5%
      (p=0.023). However, if the two patients with familial adenomatous polyposis coli
      were excluded, the comparison with the general population prevalence did not
      reach statistical significance (p=0.095). The prevalence of multiple cafe'-au
      lait macules in our patients (4/14 or 28.6%; CI:8.4-58.1%) was significantly
      higher than the general population prevalence of 5.2% (p 1/4 0.005). A notable
      finding was the presence of multiple cafe -au-lait macules in 4 of 12 juvenile
      polyposis coli/juvenile polyposis patients.Two patients with juvenile polyposis
      coli also had lentigines. In this selected case series, we observed single or
      multiple cafe-au-lait macules in a high proportion of children with the three
      types of polyps. Further studies are needed to assess a possible common pathway
      for hamartomatous polypsand cafe-au-lait macules.

PMID- 17509110
TI  - Familial Uncombable Hair Syndrome: Ultrastructural Hair Study and Response to
      Biotin.
AB  - We report a family affected to the fourth generation by uncombable hair syndrome.
      This syndrome is characterized by unruly, dry, blond hair with a tangled
      appearance. The family pedigree strongly supports the hypothesis of autosomal
      dominant inheritance; some members of the family had, apart from uncombable hair,
      minor signs of atopy and ectodermal dysplasia, such as abnormalities of the
      nails. The diagnosis was confirmed by means of extensive scanning electron
      microscopy. A trial with oral biotin 5 mg/day was started on two young patients
      with excellent results as regards the hair appearance, although scanning electron
      microscopy did not show structural changes in the hair. After a 2-year-period of
      follow-up, hair normality was maintained without biotin, while nail fragility
      still required biotin supplementation for control.

PMID- 17509111
TI  - Autosomal recessive cutis laxa in two siblings associated with blue sclera.
AB  - Cutis laxa is a clinical entity found in a heterogeneous group of genetic and
      acquired disorders characterized by premature aging of the skin with normal wound
      healing. We report two siblings born of consanguineous parents who presented with
      growth retardation, delayed developmental milestones, and the classical
      phenotypic manifestations of type 2 recessive cutis laxa. They showed remarkable
      blue sclera, which to our knowledge has not been reported previously in cutis
      laxa.

PMID- 17509113
TI  - Ehlers-Danlos syndrome and anorexia nervosa: a dangerous combination?
AB  - A 16-year-old boy with anorexia nervosa and Ehlers-Danlos syndrome presented with
      spontaneous pneumomediastinum and bradycardia.Although prior occurrences of
      pneumomediastinum and visceral perforations have been reported in adolescents
      with isolated anorexia nervosa or Ehlers-Danlos syndrome, to our knowledge this
      is the first instance to be noted in a patient with both conditions.We explore
      several possibilities regarding the etiology of his mediastinal air, but
      ultimately conclude that it was the existence of Ehlers-Danlos syndrome in the
      presence of anorexia nervosa that led to the development of this dangerous
      condition.

PMID- 17509114
TI  - Development and validation of a disease-specific quality of life questionnaire
      (EQOL) for potentially curable patients with carcinoma of the esophagus.
AB  - The objective was to develop, pretest and validate a disease-specific quality of
      life questionnaire for potentially curable patients with esophageal carcinoma,
      for use with the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC QLQ-C30) in order to assess the quality of
      life associated with the various treatment modalities available for this disease.
      Questionnaire development phase Patients were enrolled in three centres.
      Literature reviews, patients, family members, and health care professionals
      generated 195 items: symptoms (55); emotions (53); physical functioning (17);
      activities of daily living (ADL) (48); and leisure/social (22). Thirty-eight
      patients identified items of importance and assigned importance ratings on a 5
      point Likert scale. Impact scores were calculated as frequency times mean item
      importance. Item impact scores<20/100 were excluded. Pearson's correlation co
      efficients compared domains with the Medical Outcomes Study SF-20 (MOS SF-20).
      Fifteen items remained. Questionnaire validation phase EORTC QLQ-C30, Esophageal
      Quality of Life Questionnaire (EQOL), MOS SF-36 and a Global Rating of Change
      Questionnaire were completed at baseline, 1 week after baseline but prior to any
      treatment, 1 month, 3 months, and 6 months after treatment began. Reliability was
      assessed using paired samples correlations. Responsiveness was assessed between
      mean scores of changed and unchanged patients, and a responsiveness index was
      calculated. The MOS SF-36 was used for criterion validity. Construct validity
      included four a priori predictions. Sixty-five patients were enrolled in four
      centres in the validation phase. Paired samples correlations were high for all
      domains (0.749-0.889) indicating good reliability. Symptom, physical function and
      social domains were responsive to change at all time intervals (P<0.05).
      Emotional function was responsive at 1 and 3 months, activities of daily living
      (ADLs) at 1 and 6 months. Magnitude of change was significant when direction of
      change was stated. Between better and worse, magnitude of change was significant
      in all domains except at 6 months in symptoms, emotional and physical domains.
      The minimal clinically important difference was consistently around 0.5 for all
      domains. Minimal, moderate and large effect ranges were established. Only 2/16
      time intervals had poor correlations with the SF-36, establishing criterion
      validity. Of the four a priori predictions for construct validity, only the
      second part of one prediction, in the emotional function domain, was not
      confirmed. We have developed a 15-item questionnaire (EQOL) which has good
      reliability, responsiveness and validity and is now in use in studies in Canadian
      centres with the EORTC QLQ-C30.

PMID- 17509115
TI  - Validation of the Mayo Dysphagia Questionnaire.
AB  - While multiple instruments characterize upper gastrointestinal symptoms, a
      validated instrument devoted to the measurement of a spectrum of esophageal
      dysphagia attributes is not available. Therefore, we constructed and validated
      the Mayo Dysphagia Questionnaire (MDQ). The 27 items of the MDQ underwent content
      validity, feasibility, concurrent validity, reproducibility, internal
      consistency, and construct validity testing. To assess content validity, five
      esophageal subspecialty gastroenterologists reviewed the items to ensure
      inclusion of pertinent domains. Feasibility testing was done with eight
      outpatients who refined problematic items. To assess concurrent validity, 70
      patient responses on the MDQ were compared to responses gathered in a structured
      patient-physician interview. A separate group of 70 outpatients completed the MDQ
      twice to assess the reproducibility of each item. A total of 148 patients
      participated in the validation process (78 [53%] men; mean age 62). On average,
      the MDQ took 6 minutes to complete. A single item (odynophagia) tested poorly
      with a kappa value of <0.4. Otherwise, the majority of concurrent validity kappa
      values were in the good to excellent range with a mean of 0.63 (95% CI 0.22
      0.89). The majority of reproducibility kappa values were also in the good to
      excellent range with a median kappa value of 0.76 (interquartile range: 0.67
      0.81). Cronbach's alpha values were excellent in the range of 0.86-0.88. Spearman
      rank correlation coefficients to assess construct validity were also excellent in
      the range of 0.87-0.98. Thus, the MDQ is a concise instrument that demonstrates
      overall excellent concurrent validity, reproducibility, internal consistency, and
      construct validity for the features of esophageal dysphagia.

PMID- 17509116
TI  - Selective three-field lymphadenectomy for thoracic esophageal squamous carcinoma.
AB  - The purpose of this study was to examine metastasis in different nodal stations
      and the extent of lymphadenectomy for esophageal carcinoma. Eighty-seven thoracic
      esophageal squamous carcinoma patients underwent esophagectomy with two-field or
      three-field lymphadenectomy based on cervical ultrasonography. Thirty-five
      patients (40.2%) with ultrasonography-detected cervical nodes underwent cervical
      dissection. Significantly more patients with primary tumors in the upper thoracic
      esophagus had cervical dissection than patients with tumors in the middle and
      lower esophagus (66.7%vs. 30.2%, P=0.002). Metastasis to cervical, superior
      mediastinal, mid-mediastinal, and abdominal nodes were 19.5%, 25.3%, 23%, and
      24.1%, respectively. Cervical metastasis was 29.2%, 20.8%, and 10% for upper,
      middle, and lower thoracic esophageal tumors. Regional lymphadenopathy was found
      in 48 patients (55.2%) and was significantly related to cervical metastasis
      (31.3%vs. 5.1%, P=0.002). It was significantly less in upper (37.5%) than in
      middle (62.3%) and lower (60%) thoracic esophageal tumors (P=0.041). When
      cervical metastasis was included into regional lymphadenopathy, the difference
      was no longer significant (45.8%vs. 63.5%, P=0.135). Cervical dissection was
      associated with significantly more morbidities (60%vs. 34.6%, P=0.020),
      especially recurrent laryngeal nerve palsy (22.9%vs. 9.6%, P=0.089). Recurrent
      laryngeal nerve palsy was related significantly to anastomotic leakage (53.8%vs.
      13.5%, P=0.001). There was no significant difference between the 2-year survivals
      for patients with or without cervical metastasis (50.0 vs. 72.0%, P=0.094). We
      conclude that cervical metastasis is of a similar rate as metastasis to
      mediastinal or abdominal nodes. Cervical nodes should be taken as regional lymph
      nodes for thoracic esophageal cancer. Cervical dissection is associated with
      increased morbidity and should be reserved for patients who may benefit from the
      procedure. Selective three-field dissection based on ultrasonography is helpful
      in reducing surgical morbidity while increasing the completeness of resection.

PMID- 17509117
TI  - c-Myc overexpression is strongly associated with metaplasia-dysplasia
      adenocarcinoma sequence in the esophagus.
AB  - We aim to determine the expression of the proto-oncogene c-Myc in patients with
      Barrett's esophagus (BE) and esophageal adenocarcinoma, and to evaluate the
      prevalence of such expression in relation to the metaplasia-dysplasia
      adenocarcinoma sequence. BE develops as a result of a severe esophageal mucosa
      injury from gastroesophageal reflux. BE is a premalignant lesion and plays an
      important role in the development of esophageal adenocarcinoma. Several genetic
      alterations have been identified in the process that transforms a normal cell
      into a tumorous one. In the development of human tumors, one of the most
      important genes is the proto-oncogene c-Myc. The c-Myc protein expression was
      determined by immunohistochemical analysis in four different groups: 31 patients
      with normal tissue, 43 patients with BE without dysplasia, 11 patients with
      dysplasia in BE and 37 patients with esophageal adenocarcinoma. The material was
      obtained from esophageal biopsies or the dissection of patient esophagectomy
      specimens. Demographic and endoscopic data (sex, age, race and intestinal
      metaplasia extension), and morphologic and histopathologic tumor characteristics
      (deep tumor invasion, lymph node status, and tumor differentiation) were
      analyzed. The c-Myc expression was assessed using the Immunoreactive Scoring
      System (IRS). Overexpression of c-Myc was found in only 9.6% of normal tissue
      specimens, 37.2% of Barrett's esophagus, 45.5% of BE patients with dysplasia and
      73% of adenocarcinoma samples, with significant statistical difference among
      these groups. No correlation was identified when the c-Myc expression was
      compared with morphologic and histologic tumor features or endoscopic data.
      However, linear correlation of c-Myc overexpression along the metaplasia
      dysplasia-adenocarcinoma sequence was observed. This study demonstrates a
      significant increase in the expression of c-Myc in Barrett's esophagus, dysplasia
      and adenocarcinoma in relation to the control group, as well as a linear
      progression of this gene expression in this sequence. These results point out the
      importance of this marker in the development of esophageal adenocarcinoma from
      BE.

PMID- 17509118
TI  - Comparison of two fractionation regimens in the multimodal therapy of cancer of
      the esophagus.
AB  - Multimodal therapy is increasingly utilized in the management of esophageal
      cancer. The optimum dose and fraction is unclear, and this retrospective analysis
      compared two radiation regimens in multimodality regimens where the chemotherapy
      arm and the type and magnitude of surgery was constant. Ninety-three consecutive
      patients with squamous cell carcinoma or adenocarcinoma of the esophagus were
      reviewed. Forty patients received the conventional unit regimen of 44 Gy in 22
      daily fractions (2 Gy/fraction), and 40 patients received an increased dose per
      fraction (40 Gy in 15 daily fractions [2.67 Gy/fraction]). All patients received
      two courses of 5-fluorouracil and cisplatin and surgery was carried out within 8
      weeks of completing therapy. The median overall survival in the group receiving
      the increased dose per fraction group was 25 months compared with 17 months in
      the conventional dose per fraction group (P=0.08). At 1, 3, and 5 years, 66%,
      38%, and 38%, of patients in the increased dose per fraction group were alive,
      compared with 65%, 18%, and 15% in the conventional dose per fraction group
      (P=0.13), respectively. In the conventional dose per fraction group, two patients
      developed esophageal fistulae and one patient died postoperatively due to
      hemorrhage from an aorto-enteric fistula. There were no significant differences
      observed between treatment groups, but a trend toward improved efficacy appeared
      with the increased dose per fraction.

PMID- 17509119
TI  - Prospective comparison of transthoracic versus transhiatal esophagectomy
      following neoadjuvant therapy for esophageal cancer.
AB  - Transthoracic esophagectomy (TT) has been championed as a better cancer operation
      than transhiatal esophagectomy (TH) because the approach facilitates meticulous
      wide tumor excision and lymphadenectomy. However, neoadjuvant chemoradiotherapy
      (CRTS) and chemotherapy (CS) have been reported to improve outcomes, and we aimed
      to compare outcomes after multimodal therapy related to the operative approach.
      One hundred and fifty-one consecutive patients were studied prospectively. All
      patients were staged with computed tomography and endoluminal ultrasound, and
      treatment decisions were related to stage and performance status. One hundred and
      nineteen TT (median age 58 years, 92 male, 54 CRTS, 65 CS) were performed
      compared to 32 TH (median age 57 year, 27 male, 14 CRTS, 18 CS). Primary outcome
      measure was survival. Post-operative morbidity and mortality were 54% and 4%,
      respectively, after TT compared with 59% and 6% after TH (chi2 0.239 df 1,
      P=0.625). Recurrent cancer was no less frequent after TT (52%) than after TH
      (37.5%, chi2 2.151 df=1, P=0.142). Cumulative uncorrected 5-year survival was 34%
      after TT compared with 53% after TH (log rank 1.44, df=1, P=0.2298). Median
      survival was also similar in lymph node positive patients (TT vs. TH, 23 months
      vs. 22 months, respectively, log rank 0.25, df=1, P=0.6199). Despite the fact
      that patients receiving multimodal therapy and a TH esophagectomy were less fit,
      operative morbidity, mortality and recurrence were similar, and survival did not
      differ significantly when compared with multimodal TT esophagectomy.

PMID- 17509120
TI  - Circumferential and axial distribution of esophageal mucosal damage in reflux
      disease.
AB  - The aim of this study was to evaluate the axial and radial distribution of
      histological markers including hyperplasia of the basal cell layer, elongation of
      the papillae and dilatation of the intercellular spaces of the squamous
      epithelium in patients with nonerosive reflux disease compared to controls and to
      relate this to the macroscopic topography in erosive reflux disease. Two
      different study populations were included in this report. Endoscopic esophageal
      biopsies were taken from 21 healthy control subjects and 21 nonerosive reflux
      disease patients before and after 4 weeks of esomeprazole therapy. Endoscopic
      still images from 50 erosive reflux disease patients were reviewed for the radial
      orientation of LA grade A and/or B esophagitis (Los Angeles criteria for grading
      of reflux esophagitis). The 3 o'clock position of the squamocolumnar junction
      showed significantly thicker basal cell layer (P=0.011) and more intercellular
      space dilatation (P=0.01) in nonerosive reflux disease patients compared to the 9
      o'clock position. Only a significant difference in dilatation of the
      intercellular spaces (P=0.018) between nonerosive reflux disease patients and
      controls were observed in the 3 o'clock region at the squamocolumnar junction,
      whereas 1-2 cm orally, all three histological criteria differed significantly
      (P<or=0.01). After treatment, on the contrary, papillary length was significantly
      less pronounced at the squamocolumnar junction (P<0.01). Endoscopically, erosions
      were predominantly visualized in the 3 o'clock region (P<0.05). Histological
      mucosal changes in nonerosive reflux disease patients and visible mucosal
      erosions in erosive reflux disease patients occur most frequently at the same
      position, namely in the 3 o'clock quadrant in the distal esophagus. The
      histological difference between nonerosive reflux disease patients and controls
      are more distinct 1-2 cm oral to rather than at the squamocolumnar junction.
      However the effect of therapy is most pronounced at the squamocolumnar junction.

PMID- 17509121
TI  - Short-segment jejunoplasty: the option treatment in the management of benign
      esophageal stricture.
AB  - A non-dilatable benign stricture of the esophagus is a problem for the patient
      and always a challenge for the surgeon. The present study is intended to provide
      some details of surgical technique and the physiological concept that constitutes
      the basis for patient selection for short-segment jejunoplasty. In this study,
      out of 98 patients, 91 had complex stricture of the lower, and seven of the
      cervical esophagus. The main cause of stenosis in 60 patients (61.2%) was
      gastroesophageal reflux, in 34 (34.7%) post-corrosive damage, and in three (3.0%)
      it was other causes. All patients were treated by three methods of jejunoplasty:
      group I (n=54 patients) short-segment of the jejunum; group II (n=37 pts) Roux-en
      Y double tract; and group III (n=7 patients) short jejunal segment on the long
      vascular pedicle. Intraoperative complications occurred in 17 (17.34%) of the
      patients. An anastomotic leak occurred only in three (3.29%) in group I and II,
      and 1/98 patients (1.02%) died from mediastinitis. Follow-up of functional
      results for up to 36 months (average 18 months) was available in 77/97 (79.3%)
      hospital survivors. Fifty-seven (74%) patients are satisfied with their ability
      to take food, postoperative reflux was completely denied by 72 (93.5%) patients.
      Postvagotomy diarrhea was transient and gradually subsided over the course of the
      first 6 months.

PMID- 17509122
TI  - Retrograde tube drainage for esophageal anastomotic leaks and perforation.
AB  - The mortality and morbidity of esophageal anastomotic leaks or perforations
      remain high. We performed retrograde transanastomotic esophageal sump tube
      drainages for esophageal anastomotic leak or perforation in three patients. Our
      method is a modified procedure of the T-tube drainage. The Levin gastric tube was
      simply inserted into the esophagus via anastomotic leak or perforation to develop
      a defined fistula. All three patients were treated with a satisfactory outcome.
      An advantage of this method is that it is technically easy, and available for
      patients whose diseases are difficult to treat with standard T-tube drainage. In
      addition, one of our patients was successfully managed non-operatively by
      fluoroscopical guidance. This retrograde esophageal sump tube drainage was
      technically very easy, safe and useful for esophageal anastomotic leaks or
      perforations.

PMID- 17509123
TI  - Minimally invasive management of chylous fistula after esophagectomy.
AB  - Chyle leak is an unwelcome complication of esophagectomy that is associated with
      a high mortality. The diagnosis of this condition may be difficult or delayed and
      requires a high index of suspicion. Management varies from conservative treatment
      with drainage, intravenous nutrition, treatment and prevention of septic
      complications, to re-operation, either by thoracotomy or laparotomy to control
      the fistula. To reduce the mortality, early surgical intervention is advised and
      a minimally invasive approach has recently been reported in several cases. From
      June 2002 through August 2005 we have used video-assisted thoracoscopic surgery
      to diagnose and treat chyle fistulas from 6/129 (5%) patients who underwent
      esophagectomy for resectable carcinoma of the esophagus or high-grade dysplasia.
      The fistula was successfully controlled in 5/6 cases by direct thoracoscopic
      application of a suture, clips or fibrin glue. One patient required a laparotomy
      and ligation of the cysterna chyli after thoracoscopy failed to identify an
      intrathoracic source of the leak. An early minimally invasive approach can be
      safely and effectively applied to the diagnosis and management of post
      esophagectomy chylous fistula in the majority of cases. Open surgery may be
      appropriate where minimally invasive approaches fail or where the availability of
      such skills is limited.

PMID- 17509124
TI  - Characterization of telomerase-immortalized, non-neoplastic, human Barrett's cell
      line (BAR-T).
AB  - Barrett's esophagus, a metaplasia predisposed to malignant transformation, has
      been studied in vitro using esophageal adenocarcinoma cell lines. However,
      findings in such transformed cells may not be applicable to the non-neoplastic
      cells of benign Barrett's esophagus. Therefore, we have developed and
      characterized a Barrett's cell line derived from a patient without malignancy or
      dysplasia. Human Barrett's epithelial cells were immortalized with the insertion
      of hTERT (human telomerase reverse transcriptase) using a Cre-lox recombination
      system. We then examined properties of this continuous cell line, such as in
      vitro tumorigenicity, growth patterns, histological differentiation
      characteristics, karyotype, and checkpoint arrest mechanisms (e.g., p16, p21, and
      p53). Non-neoplastic Barrett's epithelial cells infected with hTERT (BAR-T cells)
      have been sustained in culture beyond 200 population doublings. BAR-T cells
      maintain a diploid chromosome number and exhibit non-neoplastic properties, such
      as contact inhibition and anchorage-dependent growth. BAR-T cells express
      differentiation Barrett's epithelial markers, such as villin and cytokeratins 4,
      8 and 18, and stain positive for Alcian blue, indicating the presence of mucin
      producing cells. Expression of checkpoint arrest proteins p21 and p53 are intact,
      while p16 expression is lost. Thus, we have created a human Barrett's cell line
      that is not malignantly transformed, and yet can be maintained indefinitely in
      culture. BAR-T cells are diploid, have histological differentiation markers
      characteristic of benign Barrett's epithelium, and also maintain appropriate
      expression of p21 and p53. This cell line should be a useful model for the study
      of the early events in carcinogenesis in Barrett's esophagus.

PMID- 17509125
TI  - Effect of celecoxib on cyclooxygenase-2 expression and possible variants in a
      patient with Barrett's esophagus.
AB  - Cyclooxygenase-2 (COX-2) expression is increased in metaplastic and dysplastic
      Barrett's esophageal epithelium and it is thought that selective COX-2 inhibitors
      could offer hope as chemoprevention therapy. The aim of the study was to
      investigate the in vivo effect of celecoxib on COX-2 expression in patients with
      Barrett's esophagus and no recent history of non-steroidal anti-inflammatory drug
      use. Endoscopic mucosal biopsy specimens were collected at baseline and after 28
      days of therapy in a patient treated with celecoxib 200 mg twice daily. Samples
      were analyzed for COX-2 expression by immunoblot analysis with chemiluminescence
      detection. COX-2 expression was found to decline 20% and 44% at two different
      biopsy sites compared to the baseline sample. Longer exposures revealed a number
      of previously unidentified proteins above and below the 67 kDa COX-2 protein
      including 38 kDa and 45 kDa proteins which were present only at study completion
      consistent with up-regulation after celecoxib therapy. Further investigations of
      the 38 kDa and 45 kDa proteins were undertaken using two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE) with immunoblot and MALDI-TOF
      (matrix assisted laser desorption ionization - time of flight) analysis but no
      matches were found and results were inconclusive. Unmatched masses from MALDI-TOF
      peptide mass fingerprinting were compared with human COX-2 (67 kDa) and COX-2b
      (39 kDa) using unspecific cleavage. Peptide sequence homology with COX-2 and COX
      2b was found for a length of 19 amino acids. Based on immunodetection, molecular
      weight and equivical MALDI-TOF results, one of these up-regulated proteins may be
      COX-2b.

PMID- 17509126
TI  - Esophageal motility disorders after gastric banding.
AB  - The long-term effects of gastric banding on esophageal function are not well
      described. This report describes a 28-year-old woman who developed signs and
      symptoms of abnormal esophageal motility and lower esophageal sphincter
      hypotension after gastric banding for morbid obesity. The current literature
      addressing the effects of gastric banding on esophageal function in light of this
      case report is discussed.

PMID- 17509127
TI  - Esophageal obstruction due to extensive intramural esophageal dissection:
      diagnosis and treatment using an endoscopic 'rendezvous' technique.
AB  - Intramural esophageal dissection is an uncommon condition which usually responds
      to conservative management. We report an unusual case of extensive dissection
      resulting in complete esophageal obstruction, and which required endoscopic
      therapy. Diagnosis was made using two endoscopes: the transoral endoscope was in
      the false esophageal lumen, while a second endoscope inserted through a pre
      existing gastrostomy was in the true esophageal lumen. Endoscopic needle knife
      incision of the entire mucosal septum resolved the patient's symptoms, and was
      performed without complication. The literature is reviewed for current knowledge
      of this condition. We also propose that 'intramural esophageal dissection' should
      be the preferred name for this condition, which at present is known by many
      names.

PMID- 17509128
TI  - Low pH gel intranasal sprays inactivate influenza viruses in vitro and protect
      ferrets against influenza infection.
AB  - BACKGROUND: Developing strategies for controlling the severity of pandemic
      influenza is a global public health priority. In the event of a pandemic there
      may be a place for inexpensive, readily available, effective adjunctive therapies
      to support containment strategies such as prescription antivirals, vaccines,
      quarantine and restrictions on travel. Inactivation of virus in the intranasal
      environment is one possible approach. The work described here investigated the
      sensitivity of influenza viruses to low pH, and the activity of low pH nasal
      sprays on the course of an influenza infection in the ferret model. METHODS:
      Inactivation of influenza A and avian reassortment influenza was determined using
      in vitro solutions tests. Low pH nasal sprays were tested using the ferret model
      with an influenza A Sydney/5/97 challenge. Clinical measures were shed virus,
      weight loss and body temperature. RESULTS: The virus inactivation studies showed
      that influenza viruses are rapidly inactivated by contact with acid buffered
      solutions at pH 3.5. The titre of influenza A Sydney/5/97 [H3N2] was reduced by
      at least 3 log cycles with one minute contact with buffers based on simple acid
      mixtures such as L-pyroglutamic acid, succinic acid, citric acid and ascorbic
      acid. A pH 3.5 nasal gel composition containing pyroglutamic acid, succinic acid
      and zinc acetate reduced titres of influenza A Hong Kong/8/68 [H3N2] by 6 log
      cycles, and avian reassortment influenza A/Washington/897/80 X A Mallard/New
      York/6750/78 [H3N2] by 5 log cycles, with 1 min contact.Two ferret challenge
      studies, with influenza A Sydney/5/97, demonstrated a reduction in the severity
      of the disease with early application of low pH nasal sprays versus a saline
      control. In the first study there was decreased weight loss in the treatment
      groups. In the second study there were reductions in virus shedding and weight
      loss, most notably when a gelling agent was added to the low pH formulation.
      CONCLUSION: These findings indicate the potential of a low pH nasal spray as an
      adjunct to current influenza therapies, and warrant further investigation in
      humans.

PMID- 17509130
TI  - Binding induced conformational changes of proteins correlate with their intrinsic
      fluctuations: a case study of antibodies.
AB  - BACKGROUND: How antibodies recognize and bind to antigens can not be totally
      explained by rigid shape and electrostatic complimentarity models. Alternatively,
      pre-existing equilibrium hypothesis states that the native state of an antibody
      is not defined by a single rigid conformation but instead with an ensemble of
      similar conformations that co-exist at equilibrium. Antigens bind to one of the
      preferred conformations making this conformation more abundant shifting the
      equilibrium. RESULTS: Here, two antibodies, a germline antibody of 36-65 Fab and
      a monoclonal antibody, SPE7 are studied in detail to elucidate the mechanism of
      antibody-antigen recognition and to understand how a single antibody recognizes
      different antigens. An elastic network model, Anisotropic Network Model (ANM) is
      used in the calculations. Pre-existing equilibrium is not restricted to apply to
      antibodies. Intrinsic fluctuations of eight proteins, from different classes of
      proteins, such as enzymes, binding and transport proteins are investigated to
      test the suitability of the method. The intrinsic fluctuations are compared with
      the experimentally observed ligand induced conformational changes of these
      proteins. The results show that the intrinsic fluctuations obtained by
      theoretical methods correlate with structural changes observed when a ligand is
      bound to the protein. The decomposition of the total fluctuations serves to
      identify the different individual modes of motion, ranging from the most
      cooperative ones involving the overall structure, to the most localized ones.
      CONCLUSION: Results suggest that the pre-equilibrium concept holds for antibodies
      and the promiscuity of antibodies can also be explained this hypothesis: a
      limited number of conformational states driven by intrinsic motions of an
      antibody might be adequate to bind to different antigens.

PMID- 17509131
TI  - Duplication of the dystroglycan gene in most branches of teleost fish.
AB  - BACKGROUND: The dystroglycan (DG) complex is a major non-integrin cell adhesion
      system whose multiple biological roles involve, among others, skeletal muscle
      stability, embryonic development and synapse maturation. DG is composed of two
      subunits: alpha-DG, extracellular and highly glycosylated, and the transmembrane
      beta-DG, linking the cytoskeleton to the surrounding basement membrane in a wide
      variety of tissues. A single copy of the DG gene (DAG1) has been identified so
      far in humans and other mammals, encoding for a precursor protein which is post
      translationally cleaved to liberate the two DG subunits. Similarly, D. rerio
      (zebrafish) seems to have a single copy of DAG1, whose removal was shown to cause
      a severe dystrophic phenotype in adult animals, although it is known that during
      evolution, due to a whole genome duplication (WGD) event, many teleost fish
      acquired multiple copies of several genes (paralogues). RESULTS: Data mining of
      pufferfish (T. nigroviridis and T. rubripes) and other teleost fish (O. latipes
      and G. aculeatus) available nucleotide sequences revealed the presence of two
      functional paralogous DG sequences. RT-PCR analysis proved that both the DG
      sequences are transcribed in T. nigroviridis. One of the two DG sequences
      harbours an additional mini-intronic sequence, 137 bp long, interrupting the
      uncomplicated exon-intron-exon pattern displayed by DAG1 in mammals and D. rerio.
      A similar scenario emerged also in D. labrax (sea bass), from whose genome we
      have cloned and sequenced a new DG sequence that also harbours a shorter
      additional intronic sequence of 116 bp. Western blot analysis confirmed the
      presence of DG protein products in all the species analysed including two teleost
      Antarctic species (T. bernacchii and C. hamatus). CONCLUSION: Our evolutionary
      analysis has shown that the whole-genome duplication event in the Class
      Actinopterygii (ray-finned fish) involved also DAG1. We unravelled new important
      molecular genetic details about fish orthologous DGs, which might help to
      increase the current knowledge on DG expression, maturation and targeting and on
      its physiopathological role in higher organisms.

PMID- 17509132
TI  - Access to electronic health knowledge in five countries in Africa: a descriptive
      study.
AB  - BACKGROUND: Access to medical literature in developing countries is helped by
      open access publishing and initiatives to allow free access to subscription only
      journals. The effectiveness of these initiatives in Africa has not been assessed.
      This study describes awareness, reported use and factors influencing use of on
      line medical literature via free access initiatives. METHODS: Descriptive study
      in four teaching hospitals in Cameroon, Nigeria, Tanzania and Uganda plus one
      externally funded research institution in The Gambia. Survey with postgraduate
      doctors and research scientists to determine Internet access patterns, reported
      awareness of on-line medical information and free access initiatives; semi
      structured interviews with a sub-sample of survey participants to explore factors
      influencing use. RESULTS: In the four African teaching hospitals, 70% of the 305
      postgraduate doctors reported textbooks as their main source of information; 66%
      had used the Internet for health information in the last week. In two hospitals,
      Internet cafes were the main Internet access point. For researchers at the
      externally-funded research institution, electronic resources were their main
      source, and almost all had used the Internet in the last week. Across all 333
      respondents, 90% had heard of PubMed, 78% of BMJ on line, 49% the Cochrane
      Library, 47% HINARI, and 19% BioMedCentral. HINARI use correlates with accessing
      the Internet on computers located in institutions. Qualitative data suggested
      there are difficulties logging into HINARI and that sometimes it is librarians
      that limit access to passwords. CONCLUSION: Text books remain an important
      resource for postgraduate doctors in training. Internet use is common, but
      awareness of free-access initiatives is limited. HINARI and other initiatives
      could be more effective with strong institutional endorsement and management to
      promote and ensure access.

PMID- 17509133
TI  - Plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR)
      and early mortality risk among patients enrolling for antiretroviral treatment in
      South Africa.
AB  - BACKGROUND: Serum concentrations of soluble urokinase-type plasminogen activator
      receptor (suPAR) have a strong independent association with HIV-1-related
      mortality. The practical utility of plasma suPAR in assessing short-term all
      cause mortality risk was evaluated in patients with advanced immunodeficiency
      enrolling in an antiretroviral treatment (ART) programme in South Africa.
      METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma
      concentrations of suPAR in patients at the time of enrollment to the ART
      programme. The association between plasma suPAR concentrations, baseline patient
      characteristics and cohort outcomes after 4 months of ART were determined.
      RESULTS: Patients (n = 293, 70% female) had a median age of 33 years and were
      followed up for a median of 5 months from enrollment. The median CD4 cell count
      was 47 cells/mul (IQR = 22-72) and 38% of patients had WHO stage 4 disease. 218
      (74%) patients remained alive after 4 months of ART; 39 (13%) died and 36 (12%)
      were lost to the programme for other reasons. Patients who died had significantly
      higher plasma suPAR concentrations compared to those who either survived (P <
      0.01) or left the programme for other reasons (P < 0.043). In multivariate
      analysis, higher log10 suPAR concentrations were significantly associated with
      lower CD4 cell counts, WHO clinical stage 4 disease and male sex. In multivariate
      analysis to identify factors associated with death, log10 suPAR concentration was
      the most strongly associated variable (P < 0.001). However, examination of
      sensitivity and specificity characteristics using receiver operating
      characteristic (ROC) analysis revealed that results from this assay did not have
      a discriminatory cut-point to provide clinically useful information. CONCLUSION:
      Plasma suPAR concentration was the strongest independent predictor of short-term
      mortality risk among patients with advanced immunodeficiency enrolling in this
      ART programme. However, lack of a discriminatory threshold did not permit this
      marker to be used to triage patients according to short-term mortality risk.

PMID- 17509134
TI  - Structure of the dimeric N-glycosylated form of fungal beta-N
      acetylhexosaminidase revealed by computer modeling, vibrational spectroscopy, and
      biochemical studies.
AB  - BACKGROUND: Fungal beta-N-acetylhexosaminidases catalyze the hydrolysis of
      chitobiose into its constituent monosaccharides. These enzymes are
      physiologically important during the life cycle of the fungus for the formation
      of septa, germ tubes and fruit-bodies. Crystal structures are known for two
      monomeric bacterial enzymes and the dimeric human lysosomal beta-N
      acetylhexosaminidase. The fungal beta-N-acetylhexosaminidases are robust enzymes
      commonly used in chemoenzymatic syntheses of oligosaccharides. The enzyme from
      Aspergillus oryzae was purified and its sequence was determined. RESULTS: The
      complete primary structure of the fungal beta-N-acetylhexosaminidase from
      Aspergillus oryzae CCF1066 was used to construct molecular models of the
      catalytic subunit of the enzyme, the enzyme dimer, and the N-glycosylated dimer.
      Experimental data were obtained from infrared and Raman spectroscopy, and
      biochemical studies of the native and deglycosylated enzyme, and are in good
      agreement with the models. Enzyme deglycosylated under native conditions displays
      identical kinetic parameters but is significantly less stable in acidic
      conditions, consistent with model predictions. The molecular model of the
      deglycosylated enzyme was solvated and a molecular dynamics simulation was run
      over 20 ns. The molecular model is able to bind the natural substrate -
      chitobiose with a stable value of binding energy during the molecular dynamics
      simulation. CONCLUSION: Whereas the intracellular bacterial beta-N
      acetylhexosaminidases are monomeric, the extracellular secreted enzymes of fungi
      and humans occur as dimers. Dimerization of the fungal beta-N
      acetylhexosaminidase appears to be a reversible process that is strictly pH
      dependent. Oligosaccharide moieties may also participate in the dimerization
      process that might represent a unique feature of the exclusively extracellular
      enzymes. Deglycosylation had only limited effect on enzyme activity, but it
      significantly affected enzyme stability in acidic conditions. Dimerization and N
      glycosylation are the enzyme's strategy for catalytic subunit stabilization. The
      disulfide bridge that connects Cys448 with Cys483 stabilizes a hinge region in a
      flexible loop close to the active site, which is an exclusive feature of the
      fungal enzymes, neither present in bacterial nor mammalian structures. This loop
      may play the role of a substrate binding site lid, anchored by a disulphide
      bridge that prevents the substrate binding site from being influenced by the
      flexible motion of the loop.

PMID- 17509135
TI  - Primary carcinoid tumor arising within mature teratoma of the kidney: report of a
      rare entity and review of the literature.
AB  - BACKGROUND: Primary carcinoid tumor arising within mature teratoma of the kidney
      is extremely rare, and their clinicopathologic features are not well described.
      Our objective was to further define the clinical features and pathologic spectra
      of primary carcinoid tumor arising within mature teratoma of the kidney. METHODS:
      Six previously reported case reports were identified using MEDLINE and a
      subsequent bibliographic search of all pertinent reports and reviews was
      performed. We also searched the electronic medical archival records of our
      institution and identified one additional unreported case. Data were extracted on
      the demographics, predisposing factors, clinical presentation, radiographic
      features, gross pathology, microscopic pathology, immunophenotype, therapy, and
      outcome of each of these seven cases. RESULTS: Primary carcinoid tumor arising
      within mature teratoma of the kidney was found at a mean age of 41.4 years. Of
      the 7 cases, 3 were female and 4 were male. Two of the 7 cases (28.6%) were
      associated with horseshoe kidney. It typically presented with abdominal pain
      without carcinoid syndrome. It typical radiologic appearance was well
      circumscribed partly calcified Bosniak II-III lesion. Histologically, the
      carcinoid tumor showed monotonous small round cells arranged in classic
      anastomosing cords/ribbons intermixed with solid nests. Surgery was curative, no
      additional treatment was required, no local recurrences occurred, and no
      metastases occurred in all 7 cases. The 3 cases with available outcome data were
      alive at the time of publication of their respective cases (mean, 5 months).
      CONCLUSION: Primary carcinoid tumor arising within mature teratoma of the kidney
      is a rare tumor that typically presents with abdominal pain without carcinoid
      syndrome. It is not associated with local recurrence and metastasis, is
      surgically curable, and has excellent prognosis.

PMID- 17509136
TI  - Diagnostic yield of quantitative endotracheal aspirates in patients with severe
      nursing home-acquired pneumonia.
AB  - INTRODUCTION: Diagnostic strategies based on tracheal aspirates in patients with
      severe nursing home-acquired pneumonia have not previously been evaluated. The
      objectives of the study were to investigate, in patients with severe nursing home
      acquired pneumonia, the diagnostic value of quantitative endotracheal aspirate
      (QEA) cultures using increasing interpretative cutoff points, as compared with
      bronchoalveolar lavage (BAL) and protected specimen brush (PSB) quantitative
      cultures. METHODS: Seventy-five nursing home patients requiring mechanical
      ventilation for suspected pneumonia were studied. Endotracheal aspirate, PSB, and
      BAL samples were obtained consecutively. The diagnostic yield of QEA at
      thresholds raging from 10(3) to 10(7) colony-forming units (cfu)/ml was assessed
      by calculating sensitivities, specificities, and accuracy rates. A receiver
      operator characteristic curve for the series of cutoff points was constructed.
      RESULTS: Forty-nine patients were diagnosed with pneumonia either by BAL (<or=
      10(4) cfu/ml) or PSB (<or= 10(3) cfu/ml). Diagnostic accuracy of QEA was most
      favorable at 10(4) cfu/ml. At this threshold, endotracheal aspirates coincided
      with both BAL and PSB in 30 cases, whereas partial agreement was observed in 14
      cases. This resulted in sensitivity and specificity of 90% (95% confidence
      interval 78% to 97%) and 77% (95% confidence interval 56% to 91%), respectively.
      QEA findings correlated significantly with both PSB and BAL quantitative cultures
      (r = 0.71 [P < 0.001] and r = 0.77 [P < 0.001], respectively). CONCLUSION: QEA
      may be used as a diagnostic tool to determine the presence of pneumonia in
      ventilated patients admitted from nursing homes when bronchoscopic procedures are
      not feasible or available.

PMID- 17509137
TI  - Cost-effectiveness analysis of a state funded programme for control of severe
      asthma.
AB  - BACKGROUND: Asthma is one of the most common chronic diseases and a major
      economical burden to families and health systems. Whereas efficacy of current
      therapeutical options has been clearly established, cost-effectiveness analysis
      of public health interventions for asthma control are scarce. METHODS: 81
      patients with severe asthma (12-75 years) joining a programme in a reference
      clinic providing free asthma medication were asked retrospectively about costs
      and events in the previous 12 months. During 12 months after joining the
      programme, information on direct and indirect costs, asthma control by lung
      function, symptoms and quality of life were collected. The information obtained
      was used to estimate cost-effectiveness of the intervention as compared to usual
      public health asthma management. Sensitivity analysis was conducted. RESULTS: 64
      patients concluded the study. During the 12-months follow-up within the
      programme, patients had 5 fewer days of hospitalization and 68 fewer visits to
      emergency/non scheduled medical visits per year, on average. Asthma control
      scores improved by 50% and quality of life by 74%. The annual saving in public
      resources was US$387 per patient. Family annual income increased US$512, and
      family costs were reduced by US$733. CONCLUSION: A programme for control of
      severe asthma in a developing country can reduce morbidity, improve quality of
      life and save resources from the health system and patients families.

PMID- 17509138
TI  - Pro-apoptotic Bid is required for the resolution of the effector phase of
      inflammatory arthritis.
AB  - Rheumatoid arthritis is an autoimmune disease characterized by hyperplasia of the
      synovial lining and destruction of cartilage and bone. Recent studies have
      suggested that a lack of apoptosis contributes to the hyperplasia of the synovial
      lining and to the failure in eliminating autoreactive cells. Mice lacking Fas or
      Bim, two pro-apoptotic proteins that mediate the extrinsic and intrinsic death
      cascades, respectively, develop enhanced K/BxN serum transfer-induced arthritis.
      Since the pro-apoptotic protein Bid functions as an intermediate between the
      extrinsic and intrinsic apoptotic pathways, we examined the role that it plays in
      inflammatory arthritis. Mice deficient in Bid (Bid-/-) show a delay in the
      resolution of K/BxN serum transfer-induced arthritis. Bid-/- mice display
      increased inflammation, bone destruction, and pannus formation compared to wild
      type mice. Furthermore, Bid-/- mice have elevated levels of CXC chemokine and IL
      1beta in serum, which are associated with more inflammatory cells throughout the
      arthritic joint. In addition, there are fewer apoptotic cells in the synovium of
      Bid-/- compared to Wt mice. These data suggest that extrinsic and intrinsic
      apoptotic pathways cooperate through Bid to limit development of inflammatory
      arthritis.

PMID- 17509139
TI  - T-helper 1 versus T-helper 2 lymphocyte immunodysregulation is the central factor
      in genesis of Burkitt lymphoma: hypothesis.
AB  - BACKGROUND: The HIV epidemic has challenged our previous understanding of endemic
      Burkitt's lymphoma. Despite the strong association of Burkitt's lymphoma and HIV
      infection in the Developed world, and against previous postulations that the
      cancer is due to immunosupression among African children, the HIV epidemic in the
      Malaria belt has not been associated with a corresponding increase in incidence
      of childhood Burkitt's lymphoma. Even outside the context of HIV infection, there
      is substantial evidence for a strong but skewed immune response towards a TH2
      response in genesis of Burkitt lymphoma. PRESENTATION OF THE HYPOTHESIS: Rather
      than a global and/or profound immunosupression, the final common pathway in
      genesis of Burkitt's lymphoma is the dysregulation of the immune response towards
      a TH2 response dominated by B-lymphocytes, and the concomitant suppression of the
      TH1 cell-mediated immune surveillance, driven by various
      viral/parasitic/bacterial infections. TESTING THE HYPOTHESIS: Case control
      studies comparing TH2 and TH1 immune responses in Burkitt lymphoma of different
      etiological types (sporadic, HIV-related, endemic and post-transplant) to
      demonstrate significant dominance of TH2 immune response in presence of poor CMI
      response as a common factor. Immunological profiling to evaluate differences
      between immune states that are associated (such as recurrent Malaria infection)
      and those that are not associated (such as severe protein-energy malnutrition)
      with Burkitt lymphoma. Prospective cohorts profiling chronology of immunological
      events leading to Burkitt lymphoma in children with EBV infection. IMPLICATIONS
      OF THE HYPOTHESIS: The dysregulation of the immune response may be the missing
      link in our understanding of Burkitt lymphomagenesis. This will provide
      possibilities for determination of risk and for control of development of
      malignancy in individuals/populations exposed to the relevant infections.

PMID- 17509140
TI  - A doxycycline-inducible urokinase receptor (uPAR) upregulates uPAR activities
      including resistance to anoikis in human prostate cancer cell lines.
AB  - BACKGROUND: The urokinase receptor (uPAR) mediates a diverse array of cellular
      processes including several events involved in prostate cancer metastasis. Many
      of these activities are initiated or enhanced by uPAR binding to its proteolytic
      ligand, urokinase (uPA). Our objective in this study was to generate and test an
      inducible lentiviral system capable of expressing uPAR and DsRed fluorescent
      protein in human prostate cancer cell lines. RESULTS: A DsRed-uPAR fusion
      construct was inserted into a lentiviral vector. Transduction of human prostate
      cancer cell lines with this virus and with a virus containing a reverse
      tetracycline transactivator (rt-TA) resulted in a stable transgene which induced
      both uPAR and DsRed proteins in a dose-responsive fashion upon stimulation with
      doxycycline. Immunoblots and immunofluorescence studies indicated no detectable
      uPAR expression in non-induced prostate cancer cell lines. Cells with induced
      uPAR demonstrated increased cellular adhesion to the matrix substrate vitronectin
      and increased net cell proliferation compared to uninduced cells. Finally,
      induced uPAR-expressing prostate cancer cells were resistant to anoikis over an
      extended time period when grown in suspension. CONCLUSION: This doxycycline
      inducible lentivirus system produces titerable levels of biologically active uPAR
      in vitro. This tool can be used to dissect cellular events following induction of
      uPAR in prostate cancer cells.

PMID- 17509141
TI  - Asymmetric lateral inhibitory neural activity in the auditory system: a
      magnetoencephalographic study.
AB  - BACKGROUND: Decrements of auditory evoked responses elicited by repeatedly
      presented sounds with similar frequencies have been well investigated by means of
      electroencephalography and magnetoencephalography (MEG). However the possible
      inhibitory interactions between different neuronal populations remains poorly
      understood. In the present study, we investigated the effect of proceeding notch
      filtered noises (NFNs) with different frequency spectra on a following test tone
      using MEG. RESULTS: Three-second exposure to the NFNs resulted in significantly
      different N1m responses to a 1000 Hz test tone presented 500 ms after the offset
      of the NFNs. The NFN with a lower spectral edge closest to the test tone mostly
      decreased the N1m amplitude. CONCLUSION: The decrement of the N1m component after
      exposure to the NFNs could be explained partly in terms of lateral inhibition.
      The results demonstrated that the amplitude of the N1m was more effectively
      influenced by inhibitory lateral connections originating from neurons
      corresponding to lower rather than higher frequencies. We interpret this effect
      of asymmetric lateral inhibition in the auditory system as an important
      contribution to reduce the asymmetric neural activity profiles originating from
      the cochlea.

PMID- 17509142
TI  - Phase variation and microevolution at homopolymeric tracts in Bordetella
      pertussis.
AB  - BACKGROUND: Bordetella pertussis, the causative agent of whooping cough, is a
      highly clonal pathogen of the respiratory tract. Its lack of genetic diversity,
      relative to many bacterial pathogens, could limit its ability to adapt to a
      hostile and changing host environment. This limitation might be overcome by phase
      variation, as observed for other mucosal pathogens. One of the most common
      mechanisms of phase variation is reversible expansion or contraction of
      homopolymeric tracts (HPTs). RESULTS: The genomes of B. pertussis and the two
      closely related species, B. bronchiseptica and B. parapertussis, were screened
      for homopolymeric tracts longer than expected on the basis of chance, given their
      nucleotide compositions. Sixty-nine such HPTs were found in total among the three
      genomes, 74% of which were polymorphic among the three species. Nine HPTs were
      genotyped in a collection of 90 geographically and temporally diverse B.
      pertussis strains using the polymerase chain reaction/ligase detection reaction
      (PCR/LDR) assay. Six HPTs were polymorphic in this collection of B. pertussis
      strains. Of note, one of these polymorphic HPTs was found in the fimX promoter,
      where a single base insertion variant was present in seven strains, all of which
      were isolated prior to introduction of the pertussis vaccine. Transcript
      abundance of fimX was found to be 3.8-fold lower in strains carrying the longer
      allele. HPTs in three other genes, tcfA, bapC, and BP3651, varied widely in
      composition across the strain collection and displayed allelic polymorphism
      within single cultures. CONCLUSION: Allelic polymorphism at homopolymeric tracts
      is common within the B. pertussis genome. Phase variability may be an important
      mechanism in B. pertussis for evasion of the immune system and adaptation to
      different niches in the human host. High sensitivity and specificity make the
      PCR/LDR assay a powerful tool for investigating allelic variation at HPTs. Using
      this method, allelic diversity and phase variation were demonstrated at several
      B. pertussis loci.

PMID- 17509143
TI  - Immunogenicity of the outer domain of a HIV-1 clade C gp120.
AB  - BACKGROUND: The possibility that a sub domain of a C clade HIV-1 gp120 could act
      as an effective immunogen was investigated. To do this, the outer domain (OD) of
      gp120CN54 was expressed and characterized in a construct marked by a re
      introduced conformational epitope for MAb 2G12. The expressed sequence showed
      efficient epitope retention on the isolated ODCN54 suggesting authentic folding.
      To facilitate purification and subsequent immunogenicity ODCN54 was fused to the
      Fc domain of human IgG1. Mice were immunised with the resulting fusion proteins
      and also with gp120CN54-Fc and gp120 alone. RESULTS: Fusion to Fc was found to
      stimulate antibody titre and Fc tagged ODCN54 was substantially more immunogenic
      than non-tagged gp120. Immunogenicity appeared the result of Fc facilitated
      antigen processing as immunisation with an Fc domain mutant that reduced binding
      to the FcR lead to a reduction in antibody titre when compared to the parental
      sequence. The breadth of the antibody response was assessed by serum reaction
      with five overlapping fragments of gp120CN54 expressed as GST fusion proteins in
      bacteria. A predominant anti-inner domain and anti-V3C3 response was observed
      following immunisation with gp120CN54-Fc and an anti-V3C3 response to the ODCN54
      Fc fusion. CONCLUSION: The outer domain of gp120CN54 is correctly folded
      following expression as a C terminal fusion protein. Immunogenicity is
      substantial when targeted to antigen presenting cells but shows V3 dominance in
      the polyvalent response. The gp120 outer domain has potential as a candidate
      vaccine component.

PMID- 17509144
TI  - Biomechanical and system analysis of the human femoral bone: correlation and
      anatomical approach.
AB  - BACKGROUND: The human femur is the subsystem of the locomotor apparatus and has
      got four levels of its organization. This phenomenon is the result of the
      evolution of the locomotor apparatus, encompassing both constitutional and
      individual variability. The main aim of this investigation was to study the
      organization of the human femur as a system of collaborating anatomical
      structures and, on the basis of system analysis, to define the less stable
      parameters, whose reorganization can cause the exchange of the system's status.
      METHODS: Twenty-five (25) linear and non-linear (angle) parameters were,
      therefore, investigated by specially designed tool and caliper on a material of
      166 macerated human femurs of adult individuals of both sexes. The absolute
      values were transformed into the relative one (1.0) by the meaning of the
      transverse diameter of the femoral diaphysis, and handled with current methods of
      descriptive statistical analysis. By the value of variance (q2), the results were
      distributed into four major classes. RESULTS: The belonging of each group to the
      class was subsequently estimated in grades. According to this method, the excerpt
      was distributed into four classes as well depending on the total grades. The
      Pearson's coefficient in each class was calculated between the relative values of
      the investigated parameters. Two generations of system parameters were
      subsequently defined and analyzed. CONCLUSION: This study has derived that the
      system meaning of each level of the femoral organization is related to the
      'shaping effect' of femoral units' functions. Inasmuch as the angular parameters
      were most instable at this system, they were defined as morphological substrates
      of the individual variety.

PMID- 17509145
TI  - Baseline characteristics influencing quality of life in women undergoing
      gynecologic oncology surgery.
AB  - BACKGROUND: Quality of life (QoL) measurements are important in evaluating cancer
      treatment outcomes. Factors other than cancer and its treatment may have
      significant effects on QoL and affect assessment of treatments. Baseline data
      from longitudinal studies of women with endometrial or ovarian cancer or adnexal
      mass determined at surgery to be benign were analyzed to determine the degree to
      which QoL is affected by baseline differences in demographic variables and
      health. METHODS: This study examined the effect of independent variables on
      domains of the Functional Assessment of Cancer Therapy (FACT-G) pre-operatively
      in gynecologic oncology patients undergoing surgery for pelvic mass suspected to
      be malignant or endometrial cancer. Patients also completed the Short Form
      Medical Outcomes Survey (SF-36) questionnaire (a generic health questionnaire
      that measures physical and mental health). Independent variables were surgical
      diagnosis (ovarian or endometrial cancer, benign mass), age, body mass index
      (BMI), educational level, marital status, smoking status, physical (PCS) and
      mental (MCS) summary scores of the SF-36. Multiple regression analysis was used
      to determine the influence of these variables on FACT-G domain scores (physical,
      functional, social and emotional well-being). RESULTS: Data were collected on 157
      women at their pre-operative visit (33 ovarian cancer, 45 endometrial cancer, 79
      determined at surgery to be benign). Mean scores on the FACT-G subscales and SF
      36 summary scores did not differ as a function of surgical diagnosis. PCS, MCS,
      age, and educational level were positively correlated with physical well-being,
      while increasing BMI was negatively correlated. Functional well-being was
      positively correlated with PCS and MCS and negatively correlated with BMI. Social
      well-being was positively correlated with MCS and negatively correlated with BMI
      and educational level. PCS, MCS and age were positively correlated with emotional
      well-being. Models that included PCS and MCS accounted for 30 to 44% of the
      variability in baseline physical, emotional, and functional well-being on the
      FACT-G. CONCLUSION: At the time of diagnosis and treatment, patients' QoL is
      affected by inherent characteristics. Assessment of treatment outcome should take
      into account the effect of these independent variables. As treatment options
      become more complex, these variables are likely to be of increasing importance in
      evaluating treatment effects on QoL.

PMID- 17509146
TI  - Revisiting the argument from fetal potential.
AB  - One of the most famous, and most derided, arguments against the morality of
      abortion is the argument from potential, which maintains that the fetus'
      potential to become a person and enjoy the valuable life common to persons,
      entails that its destruction is prima facie morally impermissible. In this paper,
      I will revisit and offer a defense of the argument from potential.First, I will
      criticize the classical arguments proffered against the importance of fetal
      potential, specifically the arguments put forth by philosophers Peter Singer and
      David Boonin, by carefully unpacking the claims made in these arguments and
      illustrating why they are flawed.Secondly, I will maintain that fetal potential
      is morally relevant when it comes to the morality of abortion, but that it must
      be accorded a proper place in the argument. This proper place, however, cannot be
      found until we first answer a very important and complex question: we must first
      address the issue of personal identity, and when the fetus becomes the type of
      being who is relevantly identical to a future person. I will illustrate why the
      question of fetal potential can only be meaningfully addressed after we have
      first answered the question of personal identity and how it relates to the human
      fetus.

PMID- 17509147
TI  - The metrics and correlates of physician migration from Africa.
AB  - BACKGROUND: Physician migration from poor to rich countries is considered an
      important contributor to the growing health workforce crisis in the developing
      world. This is particularly true for Africa. The perceived magnitude of such
      migration for each source country might, however, depend on the choice of metrics
      used in the analysis. This study examined the influence of choice of migration
      metrics on the rankings of African countries that suffered the most physician
      migration, and investigated the correlates of physician migration. METHODS:
      Ranking and correlational analyses were conducted on African physician migration
      data adjusted for bilateral net flows, and supplemented with developmental,
      economic and health system data. The setting was the 53 African birth countries
      of African-born physicians working in nine wealthier destination countries. Three
      metrics of physician migration were used: total number of physician emigres;
      emigration fraction defined as the proportion of the potential physician pool
      working in destination countries; and physician migration density defined as the
      number of physician emigres per 1000 population of the African source country.
      RESULTS: Rankings based on any of the migration metrics differed substantially
      from those based on the other two metrics. Although the emigration fraction and
      physician migration density metrics gave proportionality to the migration crisis,
      only the latter was consistently associated with source countries' workforce
      capacity, health, health spending, economic and development characteristics. As
      such, higher physician migration density was seen among African countries with
      relatively higher health workforce capacity (0.401 < or = r < or = 0.694, p < or
      = 0.011), health status, health spending, and development. CONCLUSION: The
      perceived magnitude of physician migration is sensitive to the choice of metrics.
      Complementing the emigration fraction, the physician migration density is a
      metric which gives a different but proportionate picture of which African
      countries stand to lose relatively more of its physicians with unchecked
      migration. The nature of health policies geared at health-worker migration can be
      expected to depend on the choice of migration metrics.

PMID- 17509148
TI  - Characterizing the expression of the human olfactory receptor gene family using a
      novel DNA microarray.
AB  - BACKGROUND: Olfactory receptor (OR) genes were discovered more than a decade ago,
      when Buck and Axel observed that, in rats, certain G-protein coupled receptors
      are expressed exclusively in the olfactory epithelium. Subsequently, protein
      sequence similarity was used to identify entire OR gene repertoires of a number
      of mammalian species, but only in mouse were these predictions followed up by
      expression studies in olfactory epithelium. To rectify this, we have developed a
      DNA microarray that contains probes for most predicted human OR loci and used
      that array to examine OR gene expression profiles in olfactory epithelium tissues
      from three individuals. RESULTS: We detected expression of 437 (76%) human OR
      genes in these olfactory epithelia. Interestingly, we detected widespread
      expression of OR pseudogenes, an observation that may shed light on the mechanism
      of OR gene choice in the olfactory sensory neurons. To address the hypothesis
      that OR genes may carry out additional functions, we also characterized the
      expression of OR genes in a number of non-olfactory tissues. CONCLUSION: While
      our results corroborate the functional annotation of the majority of predicted
      human odorant receptors, we find that a large number of putative human OR genes
      are expressed in non-olfactory tissues, sometimes exclusively so. Our
      evolutionary analysis of ectopically expressed human OR genes does not lend
      support to the hypothesis that these genes have alternative functions.

PMID- 17509149
TI  - Sequencing and association analysis of the type 1 diabetes-linked region on
      chromosome 10p12-q11.
AB  - BACKGROUND: In an effort to locate susceptibility genes for type 1 diabetes (T1D)
      several genome-wide linkage scans have been undertaken. A chromosomal region
      designated IDDM10 retained genome-wide significance in a combined analysis of the
      main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on
      chromosome 10p12-q11, including the putative IDDM10 region, to identify genes
      associated with T1D. RESULTS: Initially, we resequenced the functional candidate
      genes, CREM and SDF1, located in this region, genotyped 13 tag single nucleotide
      polymorphisms (SNPs) and found no association with T1D. We then undertook
      analysis of the whole 23 Mb region. We constructed and sequenced a contig tile
      path from two bacterial artificial clone libraries. By comparison with a clone
      library from an unrelated person used in the Human Genome Project, we identified
      12,058 SNPs. We genotyped 303 SNPs and 25 polymorphic microsatellite markers in
      765 multiplex T1D families and followed up 22 associated polymorphisms in up to
      2,857 families. We found nominal evidence of association in six loci (P = 0.05 -
      0.0026), located near the PAPD1 gene. Therefore, we resequenced 38.8 kb in this
      region, found 147 SNPs and genotyped 84 of them in the T1D families. We also
      tested 13 polymorphisms in the PAPD1 gene and in five other loci in 1,612 T1D
      patients and 1,828 controls from the UK. Overall, only the D10S193 microsatellite
      marker located 28 kb downstream of PAPD1 showed nominal evidence of association
      in both T1D families and in the case-control sample (P = 0.037 and 0.03,
      respectively). CONCLUSION: We conclude that polymorphisms in the CREM and SDF1
      genes have no major effect on T1D. The weak T1D association that we detected in
      the association scan near the PAPD1 gene may be either false or due to a small
      genuine effect, and cannot explain linkage at the IDDM10 region.

PMID- 17509150
TI  - Validation of a new test that assesses functional performance of the upper
      extremity and neck (FIT-HaNSA) in patients with shoulder pathology.
AB  - BACKGROUND: There is a lack of standardized tests that assess functional
      performance for sustained upper extremity activity. This study describes
      development of a new test for measuring functional performance of the upper
      extremity and neck and assesses reliability and concurrent validity in patients
      with shoulder pathology. METHODS: A series of developmental tests were conducted
      to develop a protocol for assessing upper extremity tasks that required multi
      level movement and sustained elevation. Kinematics of movement were investigated
      to inform subtask structure. Tasks and test composition were refined to fit
      clinical applicability criteria and pilot tested on 5 patients awaiting surgery
      for shoulder impingement and age-sex matched controls. Test-retest reliability
      was assessed on 10 subjects. Then a cohort of patients with mild to moderate (n =
      17) shoulder pathology and 19 controls (17 were age-sex matched to patients) were
      tested to further validate the Functional Impairment Test-Hand, and
      Neck/Shoulder/Arm (FIT-HaNSA) by comparing it to self-reported function and
      measured strength. The FIT-HaNSA, DASH and SPADI were tested on a single
      occasion. Impairments in isometric strength were measured using hand-held
      dynamometry. Discriminative validity was determined by comparing scores to those
      of age-sex matched controls (n = 34), using ANOVA. Pearson correlations between
      outcome measures (n = 41) were examined to establish criterion and convergent
      validity. RESULTS: A test protocol based on three five-minute subtasks, each
      either comprised of moving objects to waist-height shelves, eye-level shelves, or
      sustained manipulation of overhead nuts/bolts, was developed. Test scores for the
      latter 2 subtasks (or total scores) were different between controls as compared
      to either surgical-list patients with shoulder impingement or a variety of milder
      shoulder pathologies (p < 0.01). Test 1 correlated the highest with the DASH (r =
      -0.83), whereas Test 2 correlated highest with the SPADI (r = -0.76). CONCLUSION:
      Initial data suggest the FIT-HaNSA provides valid assessment of impaired
      functional performance in patients with shoulder pathology. It discriminates
      between patients and controls, is related to self-reported function, and yet
      provides distinct information. Longitudinal testing is warranted.

PMID- 17509151
TI  - Sp8 exhibits reciprocal induction with Fgf8 but has an opposing effect on
      anterior-posterior cortical area patterning.
AB  - Telencephalic patterning centers, defined by the discrete expression domains of
      distinct morphogens, Fgfs in the commissural plate (CoP), Wnts and Bmps in the
      cortical hem, and a ventral domain of Sonic hedgehog (Shh), are postulated to
      establish during development the initial patterning of the telencepahlon,
      including the neocortex. We show that the expression patterns of Sp5, Sp8, and
      Sp9, members of the Sp8-like family that are homologues of Drosophila buttonhead,
      correlate during early embryonic development with these three telencephalic
      patterning centers. To study potential functional relationships, we focused on
      Sp8, because it is transiently expressed in the CoP coincident with the
      expression of Fgf8, a morphogen implicated in area patterning of the neocortex.
      We also show that Sp8 is expressed in cortical progenitors in a high to low
      anterior-medial to posterior-lateral gradient across the ventricular zone. We
      used in utero electroporation of full-length and chimeric expression constructs
      to perform gain-of-function and loss-of-function studies of interactions between
      Sp8 and Fgf8 and their roles in cortical area patterning. We show that Fgf8 and
      Sp8 exhibit reciprocal induction in vivo in the embryonic telencephalon. Sp8 also
      induces downstream targets of Fgf8, including ETS transcription factors. In vitro
      assays show that Sp8 binds Fgf8 regulatory elements and is a direct
      transcriptional activator of Fgf8. We also show that Sp8 induction of Fgf8 is
      repressed by Emx2 in vitro, suggesting a mechanism to limit Fgf8 expression to
      the CoP. In vivo expression of a dominant negative Sp8 in the CoP indicates that
      Sp8 maintains expression of Fgf8 and also its effect on area patterning. Ectopic
      expression of Sp8 in anterior or posterior cortical poles induces significant
      anterior or posterior shifts in area patterning, respectively, paralleled by
      changes in expression of gene markers of positional identity. These effects of
      Sp8 on area patterning oppose those induced by ectopic expression of Fgf8,
      suggesting that in parallel to regulating Fgf8 expression, Sp8 also activates a
      distinct signaling pathway for cortical area patterning. In summary, Sp8 and Fgf8
      robustly induce one another, and may act to balance the anterior-posterior area
      patterning of the cortex.

PMID- 17509152
TI  - Variation of the myelin oligodendrocyte glycoprotein gene is not primarily
      associated with multiple sclerosis in the Sardinian population.
AB  - BACKGROUND: Multiple sclerosis (MS) is consistently associated with particular
      HLA-DRB1-DQB1 haplotypes. However, existing evidence suggests that variation at
      these loci does not entirely explain association of the HLA region with the
      disease. The MOG locus is a prime positional and functional candidate for such
      additional predisposing effects but the analysis is complicated by the strong,
      albeit labyrinthine pattern of linkage disequilibrium in the region. Here we have
      assessed the association of MOG variation with MS in the Sardinian population to
      see if it represents an independent contributor to MS predisposition. RESULTS:
      After re-sequencing the MOG gene in 21 healthy parents of MS patients we detected
      134 variants, 33 of which were novel. A set of 40 informative SNPs was then
      selected and assessed for disease association together with 1 intragenic
      microsatellite in an initial data set of 239 MS families. This microsatellite and
      11 SNPs were found to be positively associated with MS, using the transmission
      disequilibrium test, and were followed up in an additional 158 families (total
      families analysed = 397). While in these 397 families, 8 markers showed
      significant association with MS, through conditional tests we determined that
      these MOG variants were not associated with MS independently of the main DRB1
      DQB1 disease associations. CONCLUSION: These results indicate that variation
      within the MOG gene is not an important independent determinant of MS-inherited
      risk in the Sardinian population.

PMID- 17509153
TI  - Anomalous ion diffusion within skeletal muscle transverse tubule networks.
AB  - BACKGROUND: Skeletal muscle fibres contain transverse tubular (t-tubule) networks
      that allow electrical signals to rapidly propagate into the fibre. These
      electrical signals are generated by the transport of ions across the t-tubule
      membranes and this can result in significant changes in ion concentrations within
      the t-tubules during muscle excitation. During periods of repeated high-frequency
      activation of skeletal muscle the t-tubule K+ concentration is believed to
      increase significantly and diffusive K+ transport from the t-tubules into the
      interstitial space provides a mechanism for alleviating muscle membrane
      depolarization. However, the tortuous nature of the highly branched space-filling
      t-tubule network impedes the diffusion of material through the network. The
      effective diffusion coefficient for ions in the t-tubules has been measured to be
      approximately five times lower than in free solution, which is significantly
      different from existing theoretical values of the effective diffusion coefficient
      that range from 2-3 times lower than in free solution. To resolve this
      discrepancy, in this paper we study the process of diffusion within electron
      microscope scanned sections of the skeletal muscle t-tubule network using
      mathematical modelling and computer simulation techniques. Our model includes t
      tubule geometry, tautness, hydrodynamic and non-planar network factors. RESULTS:
      Using our model we found that the t-tubule network geometry reduced the K+
      diffusion coefficient to 19-27% of its value in free solution, which is
      consistent with the experimentally observed value of 21% and is significantly
      smaller than existing theoretical values that range from 32-50%. We also found
      that diffusion in the t-tubules is anomalous for skeletal muscle fibres with a
      diameter of less than approximately 10-20 microm as a result of obstructed
      diffusion. We also observed that the [K+] within the interior of the t-tubule
      network during high-frequency activation is greater for fibres with a larger
      diameter. Smaller skeletal muscle fibres are therefore more resistant to membrane
      depolarization. Because the t-tubule network is anisotropic and inhomogeneous, we
      also found that the [K+] distribution generated within the network was irregular
      for fibres of small diameter. CONCLUSION: Our model explains the measured
      effective diffusion coefficient for ions in skeletal muscle t-tubules.

PMID- 17509154
TI  - Purification and preliminary crystallization of alanine racemase from
      Streptococcus pneumoniae.
AB  - BACKGROUND: Over the past fifteen years, antibiotic resistance in the Gram
      positive opportunistic human pathogen Streptococcus pneumoniae has significantly
      increased. Clinical isolates from patients with community-acquired pneumonia or
      otitis media often display resistance to two or more antibiotics. Given the need
      for new therapeutics, we intend to investigate enzymes of cell wall biosynthesis
      as novel drug targets. Alanine racemase, a ubiquitous enzyme among bacteria and
      absent in humans, provides the essential cell wall precursor, D-alanine, which
      forms part of the tetrapeptide crosslinking the peptidoglycan layer. RESULTS: The
      alanine racemases gene from S. pneumoniae (alrSP) was amplified by PCR and cloned
      and expressed in Escherichia coli. The 367 amino acid, 39854 Da dimeric enzyme
      was purified to electrophoretic homogeneity and preliminary crystals were
      obtained. Racemic activity was demonstrated through complementation of an alr
      auxotroph of E. coli growing on L-alanine. In an alanine racemases photometric
      assay, specific activities of 87.0 and 84.8 U mg-1 were determined for the
      conversion of D- to L-alanine and L- to D-alanine, respectively. CONCLUSION: We
      have isolated and characterized the alanine racemase gene from the opportunistic
      human pathogen S. pneumoniae. The enzyme shows sufficient homology with other
      alanine racemases to allow its integration into our ongoing structure-based drug
      design project.

PMID- 17509155
TI  - Phospholipase C and myosin light chain kinase inhibition define a common step in
      actin regulation during cytokinesis.
AB  - BACKGROUND: Phosphatidylinositol 4,5-bisphosphate (PIP2) is required for
      successful completion of cytokinesis. In addition, both PIP2 and phosphoinositide
      specific phospholipase C (PLC) have been localized to the cleavage furrow of
      dividing mammalian cells. PLC hydrolyzes PIP2 to yield diacylglycerol (DAG) and
      inositol trisphosphate (IP3), which in turn induces calcium (Ca2+) release from
      the ER. Several studies suggest PIP2 must be hydrolyzed continuously for
      continued cleavage furrow ingression. The majority of these studies employ the N
      substituted maleimide U73122 as an inhibitor of PLC. However, the specificity of
      U73122 is unclear, as its active group closely resembles the non-specific
      alkylating agent N-ethylmaleimide (NEM). In addition, the pathway by which PIP2
      regulates cytokinesis remains to be elucidated. RESULTS: Here we compared the
      effects of U73122 and the structurally unrelated PLC inhibitor ET-18-OCH3
      (edelfosine) on cytokinesis in crane-fly and Drosophila spermatocytes. Our data
      show that the effects of U73122 are indeed via PLC because U73122 and ET-18-OCH3
      produced similar effects on cell morphology and actin cytoskeleton organization
      that were distinct from those caused by NEM. Furthermore, treatment with the
      myosin light chain kinase (MLCK) inhibitor ML-7 caused cleavage furrow regression
      and loss of both F-actin and phosphorylated myosin regulatory light chain from
      the contractile ring in a manner similar to treatment with U73122 and ET-18-OCH3.
      CONCLUSION: We have used multiple inhibitors to examine the roles of PLC and
      MLCK, a predicted downstream target of PLC regulation, in cytokinesis. Our
      results are consistent with a model in which PIP2 hydrolysis acts via Ca2+ to
      activate myosin via MLCK and thereby control actin dynamics during constriction
      of the contractile ring.

PMID- 17509156
TI  - Erythropoietin improves skeletal muscle microcirculation and tissue bioenergetics
      in a mouse sepsis model.
AB  - INTRODUCTION: The relationship between oxygen delivery and consumption in sepsis
      is impaired, suggesting a microcirculatory perfusion defect. Recombinant human
      erythropoietin (rHuEPO) regulates erythropoiesis and also exerts complex actions
      promoting the maintenance of homeostasis of the organism under stress. The
      objective of this study was to test the hypothesis that rHuEPO could improve
      skeletal muscle capillary perfusion and tissue oxygenation in sepsis. METHODS:
      Septic mice in three experiments received rHu-EPO 400 U/kg subcutaneously 18
      hours after cecal ligation and perforation (CLP). The first experiment measured
      the acute effects of rHuEPO on hemodynamics, blood counts, and arterial lactate
      level. The next two sets of experiments used intravital microscopy to observe
      capillary perfusion and nicotinamide adenine dinucleotide (NADH) fluorescence
      post-CLP after treatment with rHuEPO every 10 minutes for 40 minutes and at 6
      hours. Perfused capillary density during a three-minute observation period and
      NADH fluorescence were measured. RESULTS: rHuEPO did not have any effects on
      blood pressure, lactate level, or blood cell numbers. CLP mice demonstrated a 22%
      decrease in perfused capillary density compared to the sham group (28.5 versus
      36.6 capillaries per millimeter; p < 0.001). Treatment of CLP mice with rHuEPO
      resulted in an immediate and significant increase in perfused capillaries in the
      CLP group at all time points compared to baseline from 28.5 to 33.6 capillaries
      per millimeter at 40 minutes; p < 0.001. A significant increase in baseline NADH,
      suggesting tissue hypoxia, was noted in the CLP mice compared to the sham group
      (48.3 versus 43.9 fluorescence units [FU]; p = 0.03) and improved with rHuEPO
      from 48.3 to 44.4 FU at 40 minutes (p = 0.02). Six hours after treatment with
      rHuEPO, CLP mice demonstrated a higher mean perfused capillary density (39.4
      versus 31.7 capillaries per millimeter; p < 0.001) and a lower mean NADH
      fluorescence as compared to CLP+normal saline mice (49.4 versus 52.7 FU; p =
      0.03). CONCLUSION: rHuEPO produced an immediate increase in capillary perfusion
      and decrease in NADH fluorescence in skeletal muscle. Thus, it appears that
      rHuEPO improves tissue bioenergetics, which is sustained for at least six hours
      in this murine sepsis model.

PMID- 17509157
TI  - Re-sampling strategy to improve the estimation of number of null hypotheses in
      FDR control under strong correlation structures.
AB  - BACKGROUND: When conducting multiple hypothesis tests, it is important to control
      the number of false positives, or the False Discovery Rate (FDR). However, there
      is a tradeoff between controlling FDR and maximizing power. Several methods have
      been proposed, such as the q-value method, to estimate the proportion of true
      null hypothesis among the tested hypotheses, and use this estimation in the
      control of FDR. These methods usually depend on the assumption that the test
      statistics are independent (or only weakly correlated). However, many types of
      data, for example microarray data, often contain large scale correlation
      structures. Our objective was to develop methods to control the FDR while
      maintaining a greater level of power in highly correlated datasets by improving
      the estimation of the proportion of null hypotheses. RESULTS: We showed that when
      strong correlation exists among the data, which is common in microarray datasets,
      the estimation of the proportion of null hypotheses could be highly variable
      resulting in a high level of variation in the FDR. Therefore, we developed a re
      sampling strategy to reduce the variation by breaking the correlations between
      gene expression values, then using a conservative strategy of selecting the upper
      quartile of the re-sampling estimations to obtain a strong control of FDR.
      CONCLUSION: With simulation studies and perturbations on actual microarray
      datasets, our method, compared to competing methods such as q-value, generated
      slightly biased estimates on the proportion of null hypotheses but with lower
      mean square errors. When selecting genes with controlling the same FDR level, our
      methods have on average a significantly lower false discovery rate in exchange
      for a minor reduction in the power.

PMID- 17509158
TI  - Meiosis specific coiled-coil proteins in Shizosaccharomyces pombe.
AB  - Many meiosis-specific proteins in Schizosaccharomyces pombe contain coiled-coil
      motifs which play essential roles for meiotic progression. For example, the
      coiled-coil motifs present in Meu13 and Mcp7 are required for their function as a
      putative recombinase cofactor complex during meiotic recombination. Mcp6/Hrs1 and
      Mcp5/Num1 control horsetail chromosome movement by astral microtubule
      organization and anchoring dynein respectively. Dhc1 and Ssm4 are also required
      for horsetail chromosome movement. It is clear from these examples that the
      coiled-coil motif in these proteins plays an important role during the
      progression of cells through meiosis. However, there are still many unanswered
      questions on how these proteins operate. In this paper, we briefly review recent
      studies on the meiotic coiled-coil proteins in Sz. pombe.

PMID- 17509160
TI  - Preoperative therapy for breast cancer.

PMID- 17509162
TI  - Efficacy and safety of ixabepilone, a novel epothilone analogue.
AB  - The epothilones and their analogues are a new class of anticancer agents derived
      from the fermentation of myxobacterium Sorangium cellulosum. These compounds have
      some similarities to taxanes in targeting and stabilizing microtubules, but they
      also have important differences. Among the epothilone family, ixabepilone has
      emerged to be a semisynthetic epothilone analogue of interest. Ixabepilone has
      demonstrated consistent preclinical activity and seems active against various
      taxane-sensible and taxane-resistant cell lines, including those with
      overexpression of multidrug resistance and with mutations in the beta-tubulin
      gene. The interest of this ixabepilone has been confirmed clinically. Phase II
      clinical studies have demonstrated high activity in patients with taxane
      resistant metastatic breast cancer and in patients with other chemotherapy
      resistant tumor types.

PMID- 17509159
TI  - Current status of lupus genetics.
AB  - Over the past 40 years more than 100 genetic risk factors have been defined in
      systemic lupus erythematosus through a combination of case studies, linkage
      analyses of multiplex families, and case-control analyses of single genes.
      Multiple investigators have examined patient cohorts gathered from around the
      world, and although we doubt that all of the reported associations will be
      replicated, we have probably already discovered many of the genes that are
      important in lupus pathogenesis, including those encoding human leukocyte antigen
      DR, Fcgamma receptor 3A, protein tyrosine phosphatase nonreceptor 22, cytotoxic T
      lymphocyte associated antigen 4, and mannose-binding lectin. In this review we
      will present what is known, what is disputed, and what remains to be discovered
      in the world of lupus genetics.

PMID- 17509163
TI  - Peripheral neurotoxicity of weekly paclitaxel chemotherapy: a schedule or a dose
      issue?
AB  - PURPOSE: The rationale for intensification strategies is that more frequent
      exposure to chemotherapeutics could enhance antitumor activity. Several trials
      investigated weekly paclitaxel administration, but there are no clear data
      concerning peripheral neurotoxicity. The aim of this study was to assess the
      incidence of peripheral neurotoxicity in patients affected by advanced breast
      cancer treated with weekly paclitaxel. PATIENTS AND METHODS: Neurotoxicity was
      assessed with neurologic and neurophysiologic evaluation before treatment and
      after 12 weeks and 24 weeks. A total neurotoxicity score was assigned to each
      patient on the basis of neurophysiologic and neuropathic signs and symptom
      changes. Seventeen patients entered the study. RESULTS: After 12 weeks of
      treatment, 71% showed moderate clinical and/or neurophysiologic signs of
      neurotoxicity; after 24 weeks, the incidence of neurotoxicity increased to 96%.
      Sural amplitude at the 24-weeks examination significantly decreased from basal
      mean value (13.5 microv, standard deviation [SD] 6 microv vs. 7 microv, SD 5.9
      microv, respectively; P = 0.01), whereas median sensory amplitude decreased after
      24 weeks from 10.3 microv, SD 6.2 microv to 4.9 microv, SD 3.8 microv (P =
      0.001). In a subset of 11 patients, we obtained a follow-up examination after 6
      months from the end of treatment. In all patients, examined signs and symptoms of
      neurotoxicity improved with recovery of subjective neuropathic symptoms and
      neurophysiologic findings. CONCLUSION: Our results demonstrate, in a little
      population of patients evaluated with a comprehensive neurologic assessment, that
      weekly paclitaxel is related to a very high incidence of peripheral
      neurotoxicity. Follow-up data obtained in a subset of patients indicate that
      peripheral neurotoxicity is reversible.

PMID- 17509165
TI  - Analysis of the pathologic response to primary chemotherapy in patients with
      locally advanced breast cancer grouped according to estrogen receptor,
      progesterone receptor, and HER2 status.
AB  - PURPOSE: In clinical practice, it is possible to classify breast tumors according
      to estrogen receptor (ER), progesterone receptor (PgR), and HER2 overexpression:
      ER negative, PgR negative, and HER2 overexpressing; ER negative, PgR negative,
      and HER2 negative; ER positive, PgR positive, and HER2 negative; ER positive, PgR
      positive, and HER2 overexpressing; and the less frequent remaining 4
      combinations. The aim of this study was to determine the percentage of pathologic
      complete response (pCR) in patients with locally advanced breast cancer (LABC)
      treated with neoadjuvant or primary chemotherapy with anthracyclines and taxanes
      grouped according to ER, PgR, and HER2 status. PATIENTS AND METHODS: Patients
      with LABC treated with primary chemotherapy including anthracyclines and taxanes
      were grouped according to ER, PgR, and HER2 status; pCR rates were analyzed using
      the chi(2) test; and correlations with a P value of < or = 0.05 were considered
      statistically significant. RESULTS: A total of 103 patients were treated. Only
      100 patients were included for the analysis of pCR. Eighteen patients exhibited
      pCR. The pCR rate for each subgroup was as follows: 39.1% (9 of 23) had ER
      negative, PgR-negative, and HER2-negative disease (P < 0.01); 35.7% (5 of 14) had
      ER-negative, PgR-negative, and HER2-overexpressing disease; 33.3% (3 of 9) had ER
      positive, PgR-positive, and HER2-overexpressing disease; and 2.8% (1 of 36) had
      ER-positive, PgR-positive, and HER2-negative disease (P < 0.01). CONCLUSION: In
      patients with LABC, grouping breast tumors according to ER, PgR, and HER2 status
      can help predict pCR to primary chemotherapy.

PMID- 17509164
TI  - Doxorubicin/pemetrexed followed by docetaxel versus doxorubicin/ cyclophosphamide
      followed by docetaxel as neoadjuvant treatment for early-stage breast cancer: a
      randomized phase II trial.
AB  - BACKGROUND: Microarray gene expression profiling has indicated that complex
      molecular gene expression signatures might be predictive of outcome after
      systemic treatment for early breast cancer. Neoadjuvant systemic therapy (NST)
      with its assessment of pathologic complete response (pCR), so far the best
      surrogate parameter for cure, provides a unique opportunity to rapidly identify
      such molecular predictors. PATIENTS AND METHODS: Currently, an international,
      randomized phase II study of 2 sequential regimens as NST is being conducted in
      patients with primary invasive breast cancer T2-4a-c N0-2 M0. Patients receive 4
      cycles of doxorubicin/pemetrexed, followed by 4 cycles of docetaxel (AP-Doc) or 4
      cycles of doxorubicin/cyclophosphamide, followed by 4 cycles of docetaxel (AC
      Doc). Tumor, tissue, blood, and serum are collected at baseline and, if
      available, after 4 cycles of chemotherapy, and at surgery. The clinical
      objectives are to assess pCR rate, tumor response, rate of histologically
      negative axillary lymph nodes, disease-free survival, and safety after NST with
      AP-Doc or AC-Doc. Translational research objectives include the identification of
      differentially expressed genes predictive for the achievement of pCR after either
      treatment regimen. RESULTS: As of January 2007, 178 of the 256 patients planned
      for this study had been enrolled at 12 European centers. The recommendation after
      a planned interim safety and efficacy analysis was to continue with the trial as
      planned. CONCLUSION: We anticipate this study will provide a better understanding
      of the treatment options with pemetrexed in primary breast cancer and give
      insight into the practical robustness of the new marker sets in response
      prediction.

PMID- 17509166
TI  - Evaluation of fulvestrant in clinical practice: use of an electronic data
      registry.
AB  - BACKGROUND: Most postmenopausal women with hormone receptor-positive advanced
      breast cancer eventually develop resistance to endocrine therapy, resulting in
      disease progression and the need for further treatment. Fulvestrant's distinct
      mode of action offers the potential to overcome tumor resistance to previous
      endocrine treatments. PATIENTS AND METHODS: This observational, postmarketing,
      Web-based surveillance study collected "real-world" information on the use of,
      and the outcomes associated with, fulvestrant 250-mg-per month treatment of
      patients with advanced breast cancer in clinical practice. RESULTS: A total of
      213 postmenopausal patients with advanced breast cancer were enrolled from 34
      practices throughout the United States. Of these, 200 patients (93.9%) had
      received previous endocrine therapy. Overall, 85.4% of patients had received
      previous aromatase inhibitor treatment for early breast cancer, advanced breast
      cancer, or both. In clinical practice, fulvestrant was most frequently
      administered as a second-line (46% of patients) or a third-line endocrine
      treatment (27.7% of patients) for advanced disease. Most patients who
      discontinued fulvestrant (55.1%) subsequently received cytotoxic chemotherapy.
      Fulvestrant treatment resulted in clinical benefit for 47.9% of patients; 58
      patients (27.2%) exhibited an objective response, of whom 3 exhibited a complete
      response. The median time to response was 2.1 months, and the median duration of
      response was 7.6 months. At the time of analysis, 74.6% of patients had
      experienced disease progression; median time to progression was 4.7 months.
      CONCLUSION: These findings are similar to those reported in the clinical trial
      setting and confirm that fulvestrant has clinical activity after progression on
      previous endocrine therapy, including aromatase inhibitors.

PMID- 17509167
TI  - Multifocal male breast cancer: a case report.
AB  - Breast cancer among men is rare and accounts for < 1% of all breast cancer
      diagnoses. We report a 75-year-old man who presented with a painless breast lump
      and was found to have 2 separate foci of cancer in the same breast. Several cases
      of bilateral male breast cancer exist in the literature, but we are not aware of
      any previous reports of multifocal male breast cancer. Key issues surrounding the
      diagnosis and treatment of multifocal male breast cancer are discussed.

PMID- 17509168
TI  - Metaplastic breast carcinoma in a patient with Von Recklinghausen's disease.
AB  - Metaplastic carcinomas of the breast are uncommon lesions and account for < 5% of
      all breast malignancies. A type of metaplastic carcinoma is carcinosarcoma, an
      even more rare lesion. We present a case of carcinosarcoma in association with
      Von Recklinghausen's disease in a 60-year-old woman. Von Recklinghausen's disease
      is an autosomal dominant disorder that is localized at the long arm of chromosome
      17 and affects 1 in 4000 individuals. There are few reports on breast tumor
      development and incidence in patients with Von Recklinghausen's disease. To our
      knowledge, there has been no report of breast carcinosarcoma associated with Von
      Recklinghausen's disease. We comment on the difficulties of diagnosis and
      treatment and the possibility of breast tumors occurring more frequently in
      patients with Von Recklinghausen's disease.

PMID- 17509169
TI  - Behcet's disease.
AB  - Behcet's disease (BD) is a chronic, relapsing multisystem vasculitis with
      predominant involvement of the oral and genital mucosa. It has a worldwide
      distribution, but the prevalence is highest in Central Asia and the Far East
      (along the ancient 'Silk Route'). Genetic, environmental, immunological and
      haemostatic factors play a role in the aetiopathogenesis. The International Study
      Group for BD proposed criteria for the diagnosis of this condition, the essential
      feature being recurrent oral ulceration. Genital ulcers and skin manifestations
      are common, while ocular changes are the most important cause of morbidity.
      Almost any organ in the body can be involved, and systemic involvement may
      portend a poorer prognosis. There is no pathognomonic test for BD and the
      diagnosis is made on clinical findings. Treatment of BD would require
      multidisciplinary cooperation, and early referral to an ophthalmologist is
      advisable to prevent ocular morbidity. Topical and systemic agents (colchicine,
      dapsone and thalidomide) are useful in controlling exacerbation of the oral and
      genital ulcers. Severe disease may require immunosuppressive agents and, more
      recently, biological agents have been used successfully. It tends to follow an
      unpredictable course, and the eventual prognosis depends on the systemic
      involvement.

PMID- 17509170
TI  - Experience of setting up a genitourinary medicine in-reach clinic in a male
      prison.
AB  - A fortnightly in-reach genitourinary (GU) medicine Service to a medium security
      male prison has been provided since April 2004. Patients are seen either by
      referrals from the prison general practitioner (GP), or at an individual's
      request. Problems have arisen due to a lack of space and time - the health
      adviser and doctor have to share a room. Since the prisoners have to leave Health
      Care by 1130 hours, if one inmate has complicated issues, it can result in these
      not being dealt with, or in patients not being seen as there is no flexibility.
      There has been an unexpectedly high DNA rate, which is multifactorial. Some
      prisoners have been moved to another prison since the request to be seen was
      made, some are on court attendances or have legal visits. Additionally some men
      choose not to come when sent for on the day. A few men who attend do so
      mistakenly, thinking that GUM is the dentist. This is particularly a problem
      where English is not the first language. The attendance of prisoners at the GU
      medicine service is noted in their prison health record, with relevant
      information, such as referral for management of hepatitis C. Of the 219 men seen
      in the first year, 55% had a GU medicine screen. The most common infections were
      chlamydia 10.5%, warts 12.1% and HCV 9%. The clinic has been well supported by
      patients and prison staff. High rates of infections are being detected and
      managed. The men have been happy to be screened, and despite initial concerns all
      are happy to provide urine specimens for chlamydia screening.

PMID- 17509171
TI  - Setting up a clinical psychology service for commercial sex workers.
AB  - The objective of this study was to provide what we believe to be the first report
      of the establishment of a clinical psychology service to provide accessible
      psychological assessment, intervention and crisis support, integrated within an
      existing East London sexual health clinical and outreach service for commercial
      sex workers (CSWs). Data are presented on referral patterns, demographics,
      presenting issues to clinical psychology, interventions and outcomes for the
      first year of the service. Women presented with a range of psychosocial needs.
      Psychological interventions included direct therapy, signposting to other
      services and consultation with staff. We concluded that this flexible model of
      service provision improves access to mental health services within the context of
      a specialist sexual health and outreach service for CSWs. The provision of a
      named, female clinical psychologist who provides both the clinical sessions and
      attends outreach has been an important factor in developing trust and
      familiarity, leading to better uptake of the clinical psychology service.

PMID- 17509172
TI  - Prevalence of primary HIV-1 drug resistance in pregnant women and in newly
      diagnosed adults at Tijuana General Hospital, Baja California, Mexico.
AB  - At Tijuana General Hospital, between March 2003 and June 2005, pregnant women and
      other adults, recently identified as HIV infected, antiretroviral naive, were
      enrolled to examine the prevalence of primary HIV drug resistance. All subjects
      had the Calypte HIV-1 BED Incidence enzyme immunoassay test to identify recent
      infection. Genotypic analysis of HIV-1 protease and reverse transcriptase regions
      in plasma was performed. Forty-six subjects participated, eight (17%) men, 38
      (83%) women. Ten (22%) subjects were classified as having recent HIV infection.
      HIV genotype was performed in 41 subjects. One subject (2.5%) had a major
      mutation in the reverse transcriptase region (K219Q) conferring zidovudine
      resistance, one had a minor mutation at V118I (2.5%) and two subjects (5%) had
      minor mutation (V179D) associated with non-nucleoside reverse transcriptase
      inhibitor resistance. There were no major protease inhibitor-associated mutations
      but minor mutations were common. The prevalence of primary HIV drug resistance in
      Baja California is low.

PMID- 17509173
TI  - Evidence for the effectiveness of a chlamydia awareness campaign: increased
      population rates of chlamydia testing and detection.
AB  - The objective of this study was to determine the effectiveness of a statewide
      campaign aimed at increasing chlamydia awareness and testing among younger
      people. In November 2002, a narrowcast media campaign targeting men and women
      aged 16-29 years was launched in Victoria, Australia. This was expanded in June
      2003. Data on chlamydia testing via Medicare and chlamydia notifications, before
      and after the campaign, were compared to determine possible effects of the
      campaign on population rates of chlamydia testing and detection. During the
      campaign, chlamydia testing rates increased significantly for both women (P=0.04)
      and men (P=0.04), while testing rates before and after the campaign remained
      relatively stable. Although testing rates increased, only 4.3% of Victorian women
      and 1.9% of men aged 16-30 were tested through Medicare in 2003. The increase in
      chlamydia testing over the study period was closely paralleled by an increase in
      notification rates for chlamydia, with strong correlations between the two
      (r=0.97, P<0.001). In conclusion, an estimated minimum of A$70 was spent on the
      campaign for each additional chlamydia test performed. Testing within the
      framework of a national chlamydia screening programme may be a more cost
      effective way of increasing chlamydia testing.

PMID- 17509175
TI  - Survey of sexual dysfunction services in Bristol, UK.
AB  - We present the results of a survey of providers of sexual dysfunction services in
      Bristol. Seventeen stakeholders were identified and were sent a questionnaire to
      establish the availability of the services to clients. We enquired about
      provision of time, number and frequency of sessions offered to clients by
      different service providers. Fourteen of the seventeen (80%) questionnaires were
      returned. The total number of new patients seen was given as 1956. The private
      sector saw 90 new patients per year and 1834 were seen in the National Health
      Service (NHS) clinics. Currently there are two levels of management available for
      people with sexual problems in Bristol and these are broadly divided into the
      private/charitable and the NHS. It is important that all sectors work together to
      provide an appropriate service for the local population. There is a clear need
      for more resources for service provision for the management of sexual
      dysfunction.

PMID- 17509174
TI  - Association between active GB virus-C (hepatitis G) infection and HIV-1 disease
      in Uganda.
AB  - Although not linked to a disease, GB virus-C viraemia has been associated with an
      improved prognosis in HIV-1-co-infected individuals. Most studies have been
      conducted on men (men who have sex with men or injection drug users) infected
      with HIV-1 subtype B, whereas here we report on both male and female subjects
      from rural Uganda, predominantly infected via the heterosexual route with HIV-1
      subtypes A and D. In a longitudinal study of 272 participants, 47 were GBV-C
      positive and 181 negative, as determined by reverse transcription-polymerase
      chain reaction, in both of two plasma samples taken a median of 5.0 years apart.
      The remainder either acquired (25) or cleared (19) infection. Multilevel
      regression analyses and Cox survival analyses revealed that participants
      chronically infected with GBV-C had a slower decline in CD4(+) T cells (P<0.001)
      and increased survival time (P=0.041) compared with GBV-C RNA-negative, HIV
      positive adults. We show that the association between active GBV-C co-infection
      and improved survival of HIV-1-infected adults is not restricted to HIV subtype
      B, but is also observed in both males and females infected with HIV subtypes A
      and D.

PMID- 17509176
TI  - The treatment of pharyngeal gonorrhoea with a single oral dose of cefixime.
AB  - An audit of the efficacy treatment of pharyngeal gonorrhoea with a single oral
      dose of 400 mg of cefixime was undertaken; 83% of patients also received a single
      oral dose of azithromycin to treat possible concurrent anogenital chlamydial
      infection. Of the 54 patients studied, only one of 45 patients who attended for
      at least one test of cure had a positive culture seven days after treatment; the
      possibility of reinfection could not have been excluded. Two tests of cure were
      obtained from 18 patients. Cefixime, therefore, seems to be effective in the
      treatment of pharyngeal gonorrhoea.

PMID- 17509177
TI  - Evaluation of the fluorescent treponemal antibody absorption test for detection
      of antibodies (immunoglobulins G and M) to Treponema pallidum in serologic
      diagnosis of syphilis.
AB  - We compared the fluorescent treponemal antibody-absorption (FTA-ABS)
      (immunoglobulin (Ig)G + IgM) assay with the (micro-) Treponema pallidum
      haemagglutination assay (TPHA), the T. pallidum particle agglutination assay
      (TPPA), the Murex syphilis ICE (ICE) enzyme-linked immunosorbent assay (ELISA),
      the Diesse Enzywell TP (TP) (ELISA) using 122 serum samples and the Western blot
      (WB) assay using 42 serum samples whose results were inharmonious with other
      tests. Additionally, the Captia syphilis-M (IgM) (ELISA) were performed. All sera
      had already been examined by the rapid plasma reagin (RPR) card test, a non
      treponemal test and the TPHA, a treponemal test using routine screening tests.
      Agreements of the FTA-ABS with the TPHA test, the TPPA test, the ICE test and the
      TP test were 97.5%, 95.9%, 98.3% and 98.3%, respectively. The results suggest
      that the FTA-ABS test is a useful confirmatory test, but can be inadequate as a
      confirmatory test for serologic diagnosis of syphilis by giving equivocal and
      false-negative results even rarely.

PMID- 17509178
TI  - High coverage with HAART is required to substantially reduce the number of deaths
      from tuberculosis: system dynamics simulation.
AB  - We used a system dynamics simulation model of the transmission dynamics of drug
      sensitive tuberculosis (DSTB), multidrug-resistant tuberculosis (MDRTB) and HIV
      to estimate the impact of coverage with highly active antiretroviral therapy
      (HAART) and different cure rates for MDRTB in settings of explosive HIV epidemics
      and high MDRTB levels. Population coverage levels at 0%, 25%, 50%, 75% and 100%
      for HAART, and 5% and 80% of MDRTB treatment cure rates were simulated over a 10
      year period and cumulative deaths from tuberculosis and HIV-associated
      tuberculosis were estimated for populations with latent tuberculosis, DSTB,
      MDRTB, HIV and HIV-associated tuberculosis. Depending on levels of HAART
      population coverage, increasing MDRTB cure rates from 5% to 80% reduces
      cumulative tuberculosis deaths by 1% and 13%. High population coverage with HAART
      (75% or higher), allied with high MDRTB cure rates, reduces cumulative deaths by
      60%, with limited impact below this level. High coverage with HAART is required
      to substantially reduce the number of deaths from tuberculosis.

PMID- 17509179
TI  - Test Not Talk screening for asymptomatic men.
AB  - This audit reviews the first year's experience within a rapid comprehensive
      sexually transmitted infection (STI) and HIV screening for asymptomatic men in a
      small-integrated sexual health clinic in outer London. Men requesting STI/HIV
      screening only were offered symptom self-assessment, blood tests for syphilis and
      HIV, and first void urine tests for chlamydia and gonorrhoea. Of 468 available
      appointments, 337 were made (72%) and 303 were kept (80%). Of the 303
      attendances, 264 (87%) were first-ever attendances. Of the 303 men seen, 295
      (97.4%) underwent chlamydia and gonorrhoea testing, while 246 (80.9%) were tested
      for syphilis and HIV. No new HIV diagnoses were made. One patient was diagnosed
      with late latent syphilis and one had asymptomatic gonorrhoea, while 20 (6.6%)
      diagnoses of chlamydia were made. We believe that Test Not Talk clinics offer a
      good approach to rapid screening of asymptomatic men and to meet their sexual
      health needs.

PMID- 17509180
TI  - Retrospective review of clinical practice in chronic pelvic pain syndrome i.e.
      category III chronic prostatitis at two hospital sites over five years 2000-2005
      (an audit).
AB  - All category III chronic prostatitis cases in two hospital sites were
      retrospectively reviewed from the year 2000 until 2005. The mean age of the
      patients was 38.7 years. Of these, 56.6% were St Bartholomew's Genitourinary
      Medicine Department patients and 43.5% were Southend Genitourinary Medicine
      Clinic patients. We observed that 33.1% of these had at least one transrectal
      ultrasound of the prostate. The commonest abnormal findings in transrectal
      ultrasounds of the prostate of the series were focal calcification (16.2%),
      calculi (9.3%) and inflammatory changes (5.4%). Of this series, 35% were lost to
      follow-up. The vast majority of the remainder got better over periods ranging
      from approximately two weeks to approximately three years.

PMID- 17509181
TI  - An audit of waiting times at a district general hospital sexual health department
      -how far are we from the 48 hours target?
AB  - The Government has stated that by 2008, anyone who wants an appointment at a
      genitourinary medicine clinic should be able to get one within 48 hours. We have
      performed an audit of waiting times for appointments in our clinic and compared
      this to the most recent Health Protection Agency (HPA) audit. Our audit showed
      that 75% of people were offered an appointment within 48 hours, but only 62%
      accepted - the rest wanted to be seen later. In contrast, the HPA audit suggests
      that only 63% of patients were offered an appointment within 48 hours, and 59%
      were seen within this time frame. Our audit highlights the fact that many people
      do not want to be seen within 48 hours and call in to question the validity of
      this as a target for all patients.

PMID- 17509182
TI  - Condoms do not cover everything: an unusual presentation of herpes simplex virus
      2 infection.
AB  - We report on a patient who presented with an unusual manifestation of primary
      herpes simplex virus (HSV) infection. Furthermore, this case again shows that
      even the correct use of a condom has limited protecting value. We emphasize the
      usefulness of informing patients carefully about transmission risks of HSV.

PMID- 17509183
TI  - Reactive arthritis due to zoophilic (canine) sexual intercourse.
AB  - Reactive arthritis (ReA) is defined as a joint inflammation triggered by a
      distant infection, with no cultivable microbes in the joints. Although efforts
      have been made to characterize the microorganism linked to ReA, no definite
      common feature has so far emerged. Here we present a case of ReA which occurred
      after a zoophilic (canine genus) sexual intercourse.

PMID- 17509184
TI  - Ethambutol toxicity manifesting as acute onset psychosis.
AB  - Ethambutol is commonly used for the treatment of tuberculous and atypical
      mycobacterial infection. Central nervous system (CNS) toxicity other than optic
      neuropathy is not widely reported. A 40-year-old man with advanced HIV infection
      and Mycobacterium avium complex infection experienced rapid cognitive decline
      after commencement of ethambutol, and symptoms fully resolved with cessation.

PMID- 17509185
TI  - Genitourinary medicine funding, capacity and clinical standards of care.

PMID- 17509186
TI  - Considering causality: a response to Muula.

PMID- 17509187
TI  - The evidence for health-care transmission of HIV in Africa should determine
      prevention priorities.

PMID- 17509189
TI  - New alternative to infertility treatment for women without ovarian stimulation.
AB  - Natural cycle IVF produced the world first successful live birth, but slowly this
      treatment has been replaced by ovarian stimulated cycle IVF, because it has been
      believed ovarian stimulated cycle IVF will increase the number of available
      embryos for transfer. Therefore, it directly increases the chance of pregnancy
      from the treatment cycle. However, ovarian stimulation is always associated with
      side effects. The recovery of immature oocytes followed by in-vitro maturation
      (IVM) and IVF is an attractive alternative to stimulated cycle IVF. IVM treatment
      provides a successful option to infertile women with polycystic ovaries and
      polycystic ovary syndrome. It is now possible to combine natural cycle IVF with
      IVM as an alternative for a selected group of women with various causes of
      infertility without recourse to ovarian stimulation.

PMID- 17509190
TI  - Towards a more physiological approach to IVF.
AB  - The International Society for Mild Approaches in Assisted Reproduction (ISMAAR)
      is founded to promote a more physiological, less drug-oriented, lower risk, less
      expensive and more patient friendly approach to Assisted Reproduction embracing
      not only natural cycle treatment but also gentle stimulation protocols and in
      vitro maturation of oocytes. Recent research suggests that IVF in modified
      natural cycle/mild stimulation with antagonist is likely to replace the current
      conventional approach in down-regulated cycles. The Society will focus both on
      the basic science and clinical aspects of assisted reproduction. It will be
      committed to promoting international multi-centre scientific research, regular
      practical workshops for training and also seminars for educating assisted
      reproduction technology professionals. ISMAAR aims to establish a direct dialogue
      with the voluntary sector and politicians to campaign for IVF to be a safer,
      softer and affordable treatment globally.

PMID- 17509191
TI  - Defining IVF terminology.
AB  - Rapid recent advances in in-vitro fertilization (IVF) and in-vitro maturation
      (IVM) of human oocytes are leading to vast changes in the practice of IVF. This
      article attempts to define the various approaches to these new methods.

PMID- 17509192
TI  - Uterine abnormalities and embryo implantation: clinical opinion altered by peer
      debate.
AB  - Medical professionals often hold different views on patient treatment. This study
      assessed the degree to which these views differ and the degree to which these
      opinions changed following peer debate. The authors used an audience response
      system at an Israeli Fertility Association symposium. Clinical cases in the field
      of reproductive surgery were presented and the favoured management approach was
      recorded from each participant before and after holding peer debates. The cases
      presented were: endometrial assessment prior to artificial reproductive
      treatment, the management of thin endometrium, endometrial septum, intramural
      fibroid and hydrosalpinx. All audience responses were analysed. There was
      variability in answers in all five clinical scenarios. Before and after debates,
      the proportions of physicians preferring referral to prophylactic surgery due to
      endometrial septum, intramural fibroid and hydrosalpinx were 61% versus 59%, 12%
      versus 10% and 41% versus 37%, respectively. While these overall proportions
      remained similar, significantly more clinicians changed their approach regarding
      septum and hydrosalpinx management, compared with fibroid management (18%, 18%
      and 8% respectively, P = 0.03). Medical professionals are likely to change their
      approach in some clinical cases more than others. It is postulated that treatment
      risk and lack of good evidence account for these differences.

PMID- 17509193
TI  - Cell adhesion in mouse blastocysts.

PMID- 17509194
TI  - Randomized controlled trial of three doses of letrozole for ovulation induction
      in patients with unexplained infertility.
AB  - The aromatase inhibitor letrozole is a novel agent that can be used as an
      alternative to clomiphene citrate for ovulation induction in patients with
      unexplained infertility. The dose of letrozole used has varied between studies,
      and this study aimed to compare the three most commonly used doses: 2.5, 5 and
      7.5 mg. A total of 179 patients were randomly recruited in this prospective study
      with 58, 61 and 60 patients in each dosage group respectively. This study reports
      a significantly higher (P < 0.05) number of follicles (total, > 14 mm and > or =
      18 mm) on the day of administration of human chorionic gonadotrophin in the 7.5
      mg group, associated with significantly fewer (P < 0.05) days of stimulation.
      However the pregnancy and miscarriage rates were similar in the three groups. In
      conclusion, it seems that the use of higher doses of letrozole offers no
      advantage in terms of pregnancy rates over the lower (2.5 mg) dose.

PMID- 17509195
TI  - Establishment of the need for oestrogen during implantation in non-human
      primates.
AB  - Deprivation of oestrogen during post-ovulatory mated cycles in proven fertile
      female bonnet monkeys by tamoxifen, aromatase inhibitor or oestrogen antiserum
      resulted in inhibition of pregnancy establishment in all three groups of animals.
      However, more than 85% of the animals became pregnant within three exposures to
      proven fertile males in the control group. These results suggest the requirement
      for oestrogen in pregnancy establishment in primates. Based on this conclusion,
      it is suggested that use of a suitable and potent anti-oestrogenic compound can
      be exploited as an alternative approach to contraception.

PMID- 17509196
TI  - GnRH antagonists in ovarian stimulation for ICSI with oocyte restriction: a
      matched, controlled study.
AB  - Italian legislation regarding reproductive medicine limits the number of embryos
      transferred per attempt to three. Thus, in order to achieve pregnancy, more IVF
      cycles may be required, generating a need for methods of ovarian stimulation with
      fewer side effects. The gonadotrophin-releasing hormone (GnRH) antagonists have
      several advantages in this respect, but there is a debate regarding a possible
      lower pregnancy rate from resulting cycles. This study evaluated the clinical
      applicability of GnRH antagonists for ovarian stimulation in young women
      undergoing intracytoplasmic sperm injection (ICSI) in which only three oocytes
      can be fertilized. The 200 women treated with GnRH antagonist had a significantly
      shorter stimulation and lower gonadotrophin consumption, oestradiol
      concentration, total and mature oocyte recovery as compared with 200 matched
      controls treated with GnRH agonist. No differences were found between the groups
      in the number of normal zygotes, total cleaved, transferred and high quality
      embryos, or in the clinical outcomes. Thus, the previously reported lower
      pregnancy rate in GnRH antagonist cycles may be related to the oocyte
      characteristics. Finally, under conditions of oocyte number restriction, the GnRH
      antagonist-based cycles may be proposed as an efficacious, safe and minimally
      invasive alternative to GnRH agonist in a standard long protocol.

PMID- 17509197
TI  - TSPY gene copy number as a potential new risk factor for male infertility.
AB  - The human TSPY (testis-specific protein, Y-linked) gene family (30-60 copies) is
      situated in the MSY (male-specific) region of the Y chromosome. Testis-specific
      expression indicates that the gene plays a role in spermatogenesis. Refined
      quantitative fluorescence PCR (polymerase chain reaction) was applied to evaluate
      the relative number of TSPY copies compared with AMELY/X (amelogenin gene, Y
      linked) genes in 84 stratified infertile men and in 40 controls. A significantly
      higher number of TSPY copies was found in infertile men compared with the
      controls (P = 0.002). The diagnostic discrimination potential of the relative
      number of TSPY copies was evaluated by receiver operating characteristic curve
      analysis. TSPY/AMELY was unambiguously found to be powerful in the diagnostic
      separation of both the control samples and the infertile men, reaching a good
      level of specificity (0.642) and sensitivity (0.732) at a cut-off point of 0.46.
      The findings were supported by independently repeated studies of randomly
      selected positive samples and controls. Evaluation of the TSPY copy number offers
      a completely new diagnostic approach in relation to the genetic cause of male
      infertility. The possible effect of the copy number of TSPY genes on
      spermatogenesis may explain indiscrete pathological alterations of spermatid
      quality and quantity.

PMID- 17509198
TI  - Paternal age and outcome of intracytoplasmic sperm injection.
AB  - In a retrospective study, the outcome of intracytoplasmic sperm injection (ICSI)
      in two age groups of men was studied. Couples with male partners aged 50 years
      and over (group A) (n = 227) with mean age of 53 +/- 5 years were compared with
      couples with younger age-group male partners (group B) (n = 227) with a mean age
      of 38.4 +/- 5.8 years. The control group of younger men was selected so that the
      women's age matched between the two groups. There was no significant difference
      in pregnancy rate between the two groups (37.9 versus 36.6%; OR = 1.06, 95% CI =
      0.72-1.55). There was also no significant difference in the pregnancy rate
      between men aged 60 years and over as compared with men aged 50 to 59 years (OR =
      1.00, 95% CI 0.74-1.37). However, the long-term outcome of these pregnancies
      needs further investigation. Semen analysis showed significantly lower motility
      in group A (37.4 +/- 20.4) versus group B (46.4 +/- 15.5; P < 0.0001). There was
      a significantly higher fertilization rate in younger men (P < 0.0001; OR = 1.36,
      95% CI = 1.19-1.55), but this did not affect the pregnancy rate. In conclusion,
      it appears that paternal age has no effect on the pregnancy rate after ICSI.

PMID- 17509199
TI  - Selective visualization of the Fallopian tube with magnetic resonance imaging.
AB  - At present, X-ray hysterosalpingography is used commonly as a screening method
      for testing Fallopian tube patency, but the results are often unreliable due to
      mucous plugs or muscular contractions. Selective catheterization of the tubes
      under X-ray control is feasible, but is rarely used due to exposure of young
      individuals aiming for pregnancy to a high ionizing dose. Here, a case is
      described of a patient whose Fallopian tubes were selectively catheterized and
      visualized three-dimensionally under contrast-enhanced magnetic resonance imaging
      (MRI) guidance using a high-viscous gadoteric acid solution (Dotarem). In this
      patient, bilateral peritubal adhesions caused a blockage of the fimbrial part of
      the tube leading to transuterine spilling of tubal fluid. Laparoscopy followed by
      bilateral salpingectomy was then performed, which confirmed the three-dimensional
      MRI images, and the excised specimens were examined histologically. The
      advantages of this novel technique include the avoidance of ionizing damage to
      the gonads and the potential for development of more elaborate interventional
      methods, such as ballooning and stenting. It is intended to develop contrast MRI
      further, both for improved non-invasive visualization and for manipulative
      technology of the Fallopian tubes.

PMID- 17509200
TI  - Genes regulating trophoblast adhesion.

PMID- 17509201
TI  - Controlled natural cycle IVF: a novel approach for a dominant follicle during an
      in-vitro maturation cycle.
AB  - The objective of this retrospective analysis is to evaluate whether patients
      developing a dominant follicle in an in-vitro maturation (IVM) programme can be
      included in a natural cycle IVF (nIVF) programme. In a university teaching
      hospital, a total of 38 patients with polycystic ovarian syndrome were treated by
      metformin before undergoing an IVM cycle. Controlled nIVF was performed on seven
      patients with a dominant follicle. This paper reports three ongoing pregnancies
      from five embryo transfers in the latter group. Hence, nIVF can be a novel
      approach for women developing a dominant follicle during an IVM cycle.

PMID- 17509202
TI  - HFEA criticisms of the work of a UK surgeon are withdrawn.

PMID- 17509203
TI  - Anti-Mullerian hormone as a predictor of IVF outcome.
AB  - Serum anti-Mullerian hormone (AMH) concentration and antral follicle count (AFC)
      are two increasingly popular static measures used to predict ovarian reserve
      prior to IVF treatment. While they have been shown to be good predictors of
      oocyte yield during ovarian stimulation, their status as indicators of oocyte
      quality and pregnancy rates is currently uncertain. The present study measured
      baseline concentrations of serum AMH and FSH, and AFC from 126 women undergoing
      IVF treatment. These data were then related to IVF outcomes. As expected,
      patients with lower serum AMH and AFC produced a significantly (P < 0.001) lower
      number of oocytes compared with patients with higher serum AMH/AFC. Fertilization
      rates in patients with lower serum AMH were significantly inferior compared with
      patients with higher serum AMH, irrespective of whether IVF (P = 0.043) or
      intracytoplasmic sperm injection (P = 0.006) was used to achieve fertilization.
      These low AMH patients yielded fewer oocytes, had lower fertilization rates,
      generated fewer embryos, and had a higher incidence of miscarriage during fresh
      transfers, ultimately culminating in a halving of the pregnancy rate per IVF
      cycle compared with the high AMH group.

PMID- 17509204
TI  - What is the best site for embryo deposition? A systematic review and meta
      analysis using direct and adjusted indirect comparisons.
AB  - The site of embryo replacement has been postulated as being important to the
      success of IVF/ICSI. In order to determine the best site for embryo deposition
      during embryo transfer, a meta-analysis of randomized trials comparing different
      uterine deposition sites was undertaken. Electronic (e.g. PubMed, EMBASE,
      Cochrane Library, LILACS) and hand searches were performed to locate trials.
      Outcomes measures were the live-birth (LBR), ongoing pregnancy (OPR), and
      clinical pregnancy rates (CPR). Assessments of the endometrial cavity length
      (ECL) and the distance from the fundus to the tip of the catheter (DTC) were
      utilized. Six studies were identified, of which three were excluded. Meta
      analysis was conducted with the Mantel-Haenszel method, utilizing the fixed
      effects model. The LBR and OPR showed an increasing trend when transfers were
      performed to the lower half of the uterine cavity. For the DTC, all rates were
      significantly higher for the approximately 20 mm versus approximately 10 mm
      distance from the uterine fundus, supporting the results of the ECL analysis. The
      results of this systematic review show that there is limited evidence of the
      superiority of lower cavity transfers (e.g. approximately 20 mm) compared with
      the traditional high cavity (e.g. approximately 10 mm) transfers. More well
      designed and powered randomized trials are needed to confirm this conclusion.

PMID- 17509205
TI  - Effect of ovarian involvement on peritoneal fluid cytokine concentrations in
      endometriosis patients.
AB  - Peritoneal fluid cytokines are important for initiation and progression of
      endometriosis. The objective of this study was to compare a group of five
      cytokines (interleukins IL-1 beta, IL-6, IL-8, IL-13 and tumour necrosis factor
      alpha; TNFalpha) in peritoneal fluid of endometriosis patients with ovarian
      involvement (Group I, n = 17) to those in patients without ovarian involvement
      (Group II, n = 33) and to a reference group without endometriosis (Group III, n =
      25). All three groups were comparable regarding age, parity and body mass index.
      IL-8 concentrations were significantly higher in groups I and II compared with
      the reference group (P = 0.01 and 0.02, respectively). Similarly, TNFalpha
      concentrations were significantly higher in groups I and II compared with the
      reference group (P < 0.0001 and 0.0004, respectively). All other cytokines were
      comparable in the three groups. No significant differences were found between
      groups I and II with respect to the cytokines measured. In conclusion, peritoneal
      fluid IL-8 and TNFalpha concentrations are significantly higher in endometriosis.
      Ovarian involvement does not alter the pattern of cytokines. It appears that the
      inflammatory mediators of endometriosis are similar with and without ovarian
      involvement.

PMID- 17509206
TI  - Single embryo transfer: the role of natural cycle/minimal stimulation IVF in the
      future.
AB  - There are several good reasons to assume that single embryo transfer (SET)
      eventually will become the norm internationally in IVF treatments. A tendency is
      clearly visible, as demonstrated in the latest IVF World Report. The Nordic
      countries and Belgium have been leading the way. Sweden at present has 70% SET,
      with 5% twins and a pregnancy rate per transfer remaining constant at about 30%.
      As a consequence, recent data show a drastic reduction of the risk of prematurity
      and therefore of child morbidity and perinatal mortality. It is now time to
      discuss alternatives to the current clinical policy of quite an aggressive
      ovarian stimulation in settings where SET is the norm. When and at what
      proportion could natural cycle/soft stimulation be used? What group of patients
      would benefit? What will the consequences be in terms of efficacy, safety, cost,
      time and quality of life? Selection of the most beneficial, rather than the most
      aggressive, ovarian stimulation protocol by clinicians and by the couples
      themselves in the future may well include a much wider use of natural cycle/soft
      stimulation in IVF.

PMID- 17509207
TI  - Kisspeptin, puberty and female fertility.

PMID- 17509208
TI  - Maternal age, morphology, development and chromosome abnormalities in over 6000
      cleavage-stage embryos.
AB  - Previous studies assessing the relationship between embryo development, maternal
      age and chromosome abnormalities were either small or analysed mostly embryos not
      suitable for replacement. The present study includes >6000 embryos, including
      many suitable for replacement. Embryos with the best morphology and development
      were 44% euploid in patients younger than 35, decreasing to 21% in patients 41
      and older. The worst morphology group had only 30% normal embryos from patients
      younger than 35, and 12% in embryos from patients 41 and older. Thus
      morphological analysis was able to improve the population of normal embryos only
      from 30 to 44% in the best of cases. Regarding specific abnormalities, 20% of
      embryos were aneuploid, 32% aneuploid plus other abnormalities, and the rest had
      post-meiotic abnormalities. Of those, only aneuploidy increased with maternal
      age. There were no big differences in the frequency of chromosome abnormalities
      depending on patient indication, within a similar age group. In summary, previous
      trends detected in suboptimal embryos were also confirmed in the best embryos for
      replacement. Although dysmorphism and advanced maternal age are both related to
      chromosome abnormalities, these parameters can yield at most <50% euploid
      embryos, and other techniques such as preimplantation diagnosis are required to
      ensure that only euploid embryos are replaced.

PMID- 17509209
TI  - Outlook: Derivation of embryonic stem cells for therapy: new technologies.
AB  - Embryonic stem cells are currently derived from the inner cell mass of human
      blastocysts, generated from spare embryos donated for research. To overcome
      ethical concerns raised by destruction of the embryo, two groups of workers have
      attempted to derive these cells from isolated blastomeres of 8- to 10-cell stage
      embryos using the embryo biopsy method akin to that used in preimplantation
      diagnosis. This paper briefly discusses these two techniques in relation to the
      routine derivation of stem cells from blastocysts. Some embryological aspects of
      using the inner cell mass of blastocysts in preference to early embryonic cells
      are presented. The paper also considers some pitfalls in therapeutic cloning,
      especially in non-human primates, since legislation to allow this procedure for
      stem cell research is currently being passed in Australia.

PMID- 17509210
TI  - Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane
      review.
AB  - Gonadotrophin-releasing hormone (GnRH) antagonists suppress gonadotrophin
      secretion resulting in dramatic reduction in treatment cycle duration. Assuming
      comparable clinical outcomes, these benefits may justify changing the standard
      long GnRH agonist protocol to GnRH antagonist regimens. To evaluate the evidence,
      databases (e.g. Cochrane Library, MEDLINE, EMBASE) were electronically searched,
      hand searches were performed, and manufacturers in the field were contacted.
      Twenty-seven randomized controlled trials (RCT) fulfilled inclusion criteria for
      comparison of GnRH antagonist with long GnRH agonist protocol. Clinical pregnancy
      rate and ongoing pregnancy/live-birth rate were significantly lower in the
      antagonist group (P = 0.009; OR = 0.83, 95% CI 0.72-0.95 and P = 0.02; OR = 0.82,
      95% CI 0.68-0.97 respectively). Conversely, incidence of severe OHSS was
      significantly reduced with the antagonist protocol (P = 0.01; OR = 0.60, 95% CI
      0.40-0.88), and interventions to prevent OHSS were administered more frequently
      in the agonist group (P = 0.03; OR = 0.43, 95% CI 0.20-0.92). Concluding, GnRH
      antagonist protocols are short, simple, with good clinical outcomes and
      significant reduction in severe OHSS incidence and gonadotrophin amount; however,
      the lower pregnancy rate compared with the GnRH agonist long protocol
      necessitates counselling subfertile couples before recommending change from GnRH
      agonist to antagonist.

PMID- 17509211
TI  - Fertility testing and ICSI sperm selection by hyaluronic acid binding: clinical
      and genetic aspects.
AB  - The testis-expressed chaperone protein, HspA2 (previously creatine kinase M
      isoform) was established as a measure of human sperm cellular maturity, function
      and fertility. The presence of HspA2 in the synaptonemal complex is likely to
      link low HspA2 expression and increased frequency of chromosomal aneuploidies in
      arrested-maturity spermatozoa. A relationship also exists between HspA2
      expression in elongating spermatids and the associated spermatogenetic events,
      including plasma membrane remodelling and the formation of zona pellucida and
      hyaluronic acid (HA) binding sites. The HA receptor of mature spermatozoa, when
      coupled with HA-coated slides and/or Petri dishes, allows visual observation of
      sperm-HA binding, providing a basis for sperm maturity testing, a major
      improvement in semen evaluation, and selection of mature spermatozoa for
      intracytoplasmic sperm injection (ICSI). Thus, in HA-selected spermatozoa the
      frequency of chromosomal disomy and diploidy is reduced 4- to 6-fold compared
      with semen sperm fractions. This reduction is similar to the increase in
      numerical chromosomal aberrations in ICSI children. Combined studies of sperm
      shape and chromosome probes demonstrated that sperm morphology does not aid
      selection of haploid spermatozoa. The HA-mediated sperm selection is a novel and
      efficient technique that may alleviate potential problems related to ICSI
      fertilization with visually selected spermatozoa.

PMID- 17509212
TI  - Reducing preterm births.

PMID- 17509213
TI  - Perspectives on compensated egg-sharing in the People's Republic of China.

PMID- 17509214
TI  - Transcripts are selectively degraded in maturing oocytes.

PMID- 17509216
TI  - Even early cleavage and day 2 embryo score.

PMID- 17509218
TI  - Chicken wings and the brachial plexus.
AB  - OBJECTIVES: Some stages of limb development can now be described in terms of gene
      sequences and functions. This paper reports on the development of the brachial
      plexus (BP) in the chick. It also presents a short review on the principles of
      the peripheral nerve outgrowth. METHODS: The early development of the brachial
      plexus of chicken embryos is mapped using immunohistochemistry. This is then
      analysed in relation to the expression pattern of an axonal guidance gene,
      Semaphorin3a, by in situ hybridization studies. RESULTS: The motor axons that
      innervate the chick wing emerge from the spinal cord in spinal nerves 12-17.
      These axons grow towards the developing limb and then congregate at its base to
      form the plexus. In response to unknown cues, these axons rearrange, before
      emerging in the defined nerve trunks that innervate the limb. The developmental
      stages of BP morphogenesis described here closely correlate with previous reports
      with a significant difference of a shorter 'waiting period'. DISCUSSION: The
      development of the brachial plexus is now better understood. The waiting period,
      with more modern techniques, is observed to be shorter than previously reported.
      The significance of this and the role of the guidance molecule, Semaphorin3a, in
      this process, are being investigated and the results may have important
      implications on the management of brachial plexus palsy and other peripheral
      nerve lesions.

PMID- 17509219
TI  - Reduced cortical surface area in multiple sclerosis.
AB  - OBJECTIVE: To assess utility of cortical surface area as a measure of disease
      progression in multiple sclerosis (MS). METHODS: We measured two-dimensional
      flattened cortical surface area on high-resolution magnetic resonance imaging
      (MRI) scans obtained in 15 subjects with clinically definite MS and ten normal
      subjects. RESULTS AND DISCUSSION: Single hemisphere cortical area was reduced in
      MS patients compared with controls (96,451 versus 71,710 mm(2)). We found no
      significant relationship of cortical surface area to disability or disease
      duration. T2 lesion load was negatively correlated with two-dimensional cortical
      surface area (r=-0.62). CONCLUSION: Cortical surface area is decreased in MS and
      may be a useful measure of disease progression.

PMID- 17509220
TI  - The role of microglia/macrophage system in the tissue response to I-125
      interstitial brachytherapy of cerebral gliomas.
AB  - OBJECTIVE: To study histopathologic changes and the role of the
      microglia/macrophage cell in the therapeutic effect of I-125 interstitial
      brachytherapy on the cerebral gliomas. METHODS: Out of a series of 60 cases with
      cerebral astrocytomas and other brain tumors treated with I-125 interstitial
      brachytherapy, autopsy materials were available in ten cases 0.75 and 60 months
      after irradiation. The patients were treated with the maximum dosage (60 Gy) on
      the tumor periphery. Besides the routine hematoxylin-eosine and Mallory's PTAH
      trichrome staining, immunohistochemical reactions were carried out for CD15,
      CD31, CD34, CD45, CD68, CPM, HAM56 and HLR-DR antigens on paraffin sections to
      study immunologic phenotypic characteristics of the reaction cell population
      around gliomas after I-125 treatment. RESULT: One month after irradiation, a
      necrotic zone developed around the I-125 seeds within the 72 Gy isodose curve.
      Histologically, there was a fresh coagulation necrosis in the center of the
      lesion. Reactive zone has not yet developed but scattered interstitial and
      perivascular CD68 positive macrophages were present in the surrounding brain
      tissues. Six months after the I-125 isotope treatment, a reactive zone developed:
      a microglial rim around the necrosis tissue, and a broad area of proliferating
      vessels and glial fibrillary acidic protein (GFAP) positive astroglial cells
      which contained CD68 positive activated microglial and macrophage cells. Fifty
      four months after I-125 interstitial irradiation, the necrotic center became
      colliquative and cystic. The microglial rim was replaced by round end stage (HLR
      DR and CD31 positive) macrophages. The reactive zone was characterized by
      astrocytic gliosis but vascular proliferation and macrophages were lacking.
      CONCLUSION: Results of the present immunohistochemical study suggest that the
      early lesions are characterized by migrating macrophages apparently concerned
      with the removal of necrotic debris. The established phase of reactive zone
      around the necrotic center is characterized by a narrow inner rim of microglial
      accumulation and a broad outer area characterized by astrocytic gliosis, vascular
      proliferation, activated microglia and infiltration by macrophages. In the burned
      out phases of I-125 interstitial brachytherapy of gliomas, the necrosis undergoes
      liquefaction and the microglial rim is replaced by astrocytic gliosis which can
      be considered as equivalent to the scar tissue formed around necrosis outside the
      central nervous system.

PMID- 17509221
TI  - Molecular genetic analysis of BAX and cyclin D1 genes in patients with malignant
      glioma.
AB  - INTRODUCTION AND OBJECTIVES: Brain tumorigenesis is a complex process involving
      multiple genetic alterations. Cyclin D1 and BAX genes are two of the most
      important regulators in controlling the normal proliferation and apoptosis of
      cells, respectively. In this study, we analysed the possibilities of involvement
      of cyclin D1 and BAX genes in the gliomagenesis. METHODS AND RESULTS: In
      determining gene alterations of exon 4 of cyclin D1 gene and exon 6 of BAX gene,
      all samples were amplified by polymerase chain reaction (PCR) and subsequently by
      direct sequencing. Our results showed a frameshift mutation (G base deletion) at
      nucleotide 82 of codon 28 in exon 4 of the cyclin D1 gene and another frameshift
      mutation with a deletion of C base at nucleotide 153 of exon 6 of the BAX gene in
      two separate cases of a glioblastoma multiform (WHO Grade IV) sample. CONCLUSION:
      These findings suggest that both cyclin D1 and BAX genes alteration are rarely
      found in brain tumors. However, the alteration might cause a significant effect
      of the normal protein production and this might contribute to the development of
      brain tumorigenesis in Malaysian patients.

PMID- 17509222
TI  - Apolipoprotein E modifies the CNS response to injury via a histamine-mediated
      pathway.
AB  - Recent evidence demonstrates that apolipoprotein E (apoE) influences the central
      nervous system (CNS) response to both acute and chronic injury. To address the
      mechanisms by which apoE influences neurological disease, we examined
      differential gene expression in the brains of apoE transgenic mice after closed
      head injury. Apart from confirming the knockout of apoE, the largest differential
      gene expression occurred for the interleukin-9 receptor (IL-9R), which was > 100
      fold up-regulated in apoE-deficient versus wild-type mice. We observed a similar
      pattern of posttraumatic IL-9R up-regulation in APOE4 targeted replacement mice
      as compared with their APOE3 counterparts. This difference in gene expression was
      associated with increased neuronal protein expression of IL-9R in E4 animals
      compared with E3 as demonstrated by immunohistochemistry. The consequence of IL
      9R binding in mast cells is the induction of proliferation and differentiation.
      This indirectly favors degranulation and release of histamine and inflammatory
      mediators, which have previously been demonstrated to exacerbate secondary
      neuronal injury. We found that apoE-deficient animals had increased levels of
      systemic histamine after injury and that pre-treatment with antihistamines
      improved functional outcomes in apoE-deficient but not wild-type animals after
      head injury. These results suggest that apoE modifies secondary neuronal injury
      caused by histamine release and are consistent with previous observations that
      apoE affects the CNS inflammatory response in an isoform-specific manner.

PMID- 17509223
TI  - Diffusion weighted MRI in the early phase after electroconvulsive therapy.
AB  - Although cognitive side effects may occur after electroconvulsive therapy (ECT),
      no structural brain abnormalities have been detected after ECT with conventional
      magnetic resonance imaging (MRI). Transient disturbances of memory function are
      common findings after ECT indicating functional compromise. Diffusion weighted
      imaging (DWI) has been shown to be sensitive to focal tissue changes associated
      with compromise of energy metabolism in cerebral ischemia and after prolonged
      ictal activity. We used conventional MRI and DWI in an exploratory study
      examining ten patients after treatment with ECT, eight of whom experienced short
      lasting memory disturbances. MRI and DWI showed no definite signal abnormalities
      on qualitative and quantitative analysis. In three patients, equivocal marginal
      DWI hyperintensity was noted in the hippocampal formation. These findings are in
      line with previous negative studies using conventional MRI. Higher resolution DWI
      and serial imaging may be necessary to visualize possible minimal signal changes
      after ECT.

PMID- 17509224
TI  - Slow oscillations in middle cerebral artery cerebral blood flow velocity and
      aging.
AB  - OBJECTIVE: A recent study using near infrared spectroscopy (NIRS) showed that low
      frequency oscillations of regional cerebral blood flow (CBF) decline with age.
      Using transcranial Doppler ultrasound (TCD), it is possible to monitor similar
      fluctuations in cerebral blood velocity (CBV) in basal cerebral vessels. Such
      oscillations have been used widely in the assessment of cerebral autoregulation.
      We postulated that it should be possible to observe similar age related
      reductions in the amplitude of slow waves recorded using TCD. METHODS: We studied
      187 patients with head injury, who were admitted to Addenbrooke's Neuro Critical
      Care unit between 1992 and 1998. Intermittent recordings of CBV were undertaken
      using TCD, which were subsequently analysed using software developed in-house.
      Power spectra were computed in the very low frequency (VLF: 0.01-0.05 Hz) and low
      frequency (LF: 0.07-0.11 Hz) ranges for all signals and a regression analysis was
      performed to assess the correlation between power in each frequency band and age.
      RESULTS: No significant correlation was found between VLF or LF power and age
      (VLF: r=0.037; p=0.63; LF: r=-0.05, p=0.517). DISCUSSION: While remaining
      cogniscent of the complex nature of our patient group, we find that age dependent
      reductions in CBF oscillations seen using NIRS do not translate to recordings of
      CBV in the middle cerebral artery in patients with head injury.

PMID- 17509225
TI  - Failure to improve the effect of thrombolysis by memantine in a rat embolic
      stroke model.
AB  - OBJECTIVES: Partial and delayed recanalization is a regular finding after
      thrombolysis in stroke patients who may benefit from additional therapy with
      neuroprotectants. To translate this scenario into an experiment, memantine was
      combined with thrombolysis in an embolic stroke model and tissue outcome was
      assessed in terms of complete and incomplete damage. METHODS: Tissue plasminogen
      activator (tPA, 5 mg/kg, b.w.) was administered 1.5 or 3.5 hours after embolic
      middle cerebral artery (MCA) occlusion in rats. In both groups, rats were
      assigned to additional therapy with memantine (10 mg/kg, i.p.) or saline
      injection. Ischemia and eventual reperfusion were continuously monitored by laser
      Doppler flowmetry. Reperfusion was defined as a lasting increase in post
      thrombolytic cerebral blood flow to >60% of baseline (complete) or to a lesser
      degree (partial). Experiments were terminated 6 hours post-occlusion to obtain
      quantitative histopathology. RESULTS: tPA induced complete or partial
      recanalization in 54% of treated animals. Successful reperfusion reduced total
      ischemic lesion volume by 42% compared with non-reperfused animals (p<0.05), but
      increased significantly the percentage of scattered neuronal injury from 25.6
      (non-reperfusion) to 36.3% (reperfusion, p<0.05). Memantine did not improve the
      effect of tPA-induced recanalization on infarct morphology whether applied at 1.5
      or 3.5 hours post-occlusion. DISCUSSION: We conclude from our experiments that
      add-on therapy with memantine did not alter the effect of thrombolysis in an
      embolic stroke model. Recanalization appears to be a prerequisite to confer
      neuroprotective effects.

PMID- 17509226
TI  - NMDA receptor and iNOS are involved in the effects of ginsenoside Rg1 on
      hippocampal neurogenesis in ischemic gerbils.
AB  - OBJECTIVE: Transient global ischemia increases neurogenesis in the dentate gyrus
      of adult rodents and this may have a functional relevance. The aim of the present
      study was to explore the possible mechanisms underlying the effects of
      ginsenoside Rg1 on hippocampal neurogenesis in adult gerbils suffered from global
      ischemia. METHODS: Experimental groups include: Group 1: sham operation; Group 2:
      sham operation + MK-801 (3 mg/kg); Group 3: ischemia only; Group 4: ischemia + MK
      801; Group 5: ischemia + Rg1 (5 mg/kg); Group 6: ischemia + Rg1 + MK-801. At the
      tenth day after ischemia, six gerbils from Groups 1, 3 and 5 were killed and the
      activity of inducible nitric oxide synthase (iNOS) in the cortex and hippocampus
      was measured. The rest animals were given bromodeoxyuridine (BrdU, 50 mg/kg)
      every 4 hours for 12 hours at the tenth day after ischemia and perfused 24 hours
      after the last injection of BrdU. Immunohistochemistry was performed to identify
      proliferating cells in the dentate gyrus. RESULTS: Ginsenoside Rg1 increased the
      magnitude of ischemia induced proliferation of hippocampal progenitor cells and
      enhanced the activity of iNOS in both the hippocampus and cortex. Systematic
      injection of MK-801 completely blocked the proliferation increasing effect of
      Rg1. CONCLUSION: Ginsenoside Rg1 increases neurogenesis after transient global
      ischemia. The mechanisms underlying this effect may involve activation of iNOS
      activity and N-methyl-D-aspartate (NMDA) receptors in the brain.

PMID- 17509227
TI  - Effects of tissue plasminogen activator on cerebral microvessels of rats during
      focal cerebral ischemia and reperfusion.
AB  - The time window in the treatment of ischemic stroke with tissue plasminogen
      activator (tPA) is narrow, arbitrarily within 3 hours after the onset of symptom.
      Hemorrhagic transformation resulting from cerebral ischemia may be related to
      damage of the microvascular basal lamina of the brain, which may in turn cause
      microvascular fibrin deposition and aggravate cerebral ischemia. Here, we
      investigated the effect of tPA on the microvascular tissue changes during
      cerebral ischemia/reperfusion. Sprague-Dawley rats were subjected to focal
      cerebral ischemia by ligation of the right middle cerebral artery and bilateral
      common carotid arteries for 90 minutes. Sixty minutes after the onset of
      ischemia, escalated dosages of tPA from 2.5 to 10 mg/kg or saline were
      intravenously infused for 60 minutes. Twenty-four hours after reperfusion, the
      animals were allowed to be killed for examination. Low dosage of tPA (2.5-7.5
      mg/kg) reduced post-ischemic brain infarction, suppressed metalloproteinase 2
      (MMP-2) activity and restored blood-brain barrier (BBB) integrity. In contrast,
      high dose of tPA (10 mg/kg) aggravated brain infarction, increased MMP-2 activity
      and exacerbated BBB disruption. Cerebral ischemia/reperfusion decreased the
      immunoreactivity of both collagen type IV- and laminin-positive microvessels,
      whereas the low dosage of tPA (2.5-7.5 mg/kg) attenuated the reduction. When
      these molecules in whole cortical tissues were analysed, tPA dosage-dependently
      decreased the total content of collagen type IV, laminin and fibronectin.
      Although the detailed mechanisms regarding the action of tPA are yet to be
      investigated, our findings demonstrate that the detrimental effect of tPA was
      mediated, at least in part, through the destruction of the basal lamina in the
      cerebral microvessels by activating MMP-2.

PMID- 17509228
TI  - Pituitary dysfunction after aneurysmal subarachnoid hemorrhage.
AB  - Patients recovering from aneurysmal SAH often complain about weakness, fatigue
      and impaired cognitive skills. Pituitary dysfunction might be one possible reason
      for these complaints, as in patients with traumatic brain injury, hypopituitarism
      is known to be a common complication. There are only a few studies dealing with
      this problem in SAH patients, but these studies suggest that pituitary
      disturbances are very frequent after aneurysmal SAH. But anterior pituitary lobe
      disturbances might not be the only one responsible for some complaints or
      complications in patients suffering from aneurysmal SAH. Hyponatremia in the
      early state after SAH could be a hint for posterior pituitary lobe dysfunction.

PMID- 17509229
TI  - The effects of L-3,4-dihydroxyphenylalanine and dopamine agonists on dopamine
      neurons in the progressive hemiparkinsonian rat models.
AB  - OBJECTIVES: Dopamine replacement with the precursor L-3,4-dihydroxyphenylalanine
      (L-DOPA) and dopamine receptor agonists is the standard therapy for the
      symptomatic treatment of Parkinson's disease (PD). Whether L-DOPA and dopamine
      agonists may either accelerate or slow the degeneration of dopamine neurons is
      still controversial with conflicting data from both in vitro and in vivo
      experiments. We aimed to verify the influence of L-DOPA and receptor-selective
      dopamine agonists on dopamine neurons in the progressive hemiparkinsonian rat
      models. METHODS: We administered different doses of L-DOPA, D1 selective agonist
      SKF38393, D2 selective agonist quinpirole and D2/D3 agonist pramipexole
      intraperitoneally for 9 weeks to the rats with progressive nigrostriatal lesions
      produced by injecting 6-hydroxydopamine (6-OHDA) into the striatum. After 3, 6
      and 9 weeks of administration of dopaminergic agents, we performed the behavioral
      test using the forepaw adjusting step (FAS) test and anatomical analysis using
      tyrosine hydroxylase (TH) immunohistochemical staining and TH western blots.
      RESULTS: Only in the high dose (100 mg/kg/d) L-DOPA treated rats, TH
      immunoreactive (TH-IR) cells were significantly decreased compared with other
      groups (p<0.01). We could not detect any influence of dopamine agonists on the
      behavior or the degeneration of dopaminergic neurons, regardless of their
      receptor selectivity. DISCUSSION: In conclusion, we demonstrated the potential
      toxicity of high dose of L-DOPA, but did not observe any protective effect of
      dopamine agonists in the progressive hemiparkinsonian rat models.

PMID- 17509230
TI  - Window narrowing: a new method for standardized assessment of the tissue at risk
      maximum of infarction in CT based brain perfusion maps.
AB  - BACKGROUND: Mapping of brain perfusion using bolus tracking methods is
      increasingly used to assess the amount and severity of cerebral ischemia in acute
      stroke. Using relative perfusion maps, however, it is difficult to identify the
      tissue at risk-maximum (TARM) of infarction with sufficient reliability and
      reproducibility. METHODS: We analysed 76 perfusion computed tomography (PCT)
      derived maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and time
      to-peak (TTP) in 40 acute stroke patients using multidetector row technology and
      standard software (Somatom VolumeZoom, Siemens, Germany). 'Window narrowing' of
      the color maps was performed until color homogenisation of the contralateral
      unaffected hemisphere was reached. Tissue still depictable on the affected
      hemisphere after sufficient window narrowing was defined as the TARM. We analysed
      presence and size of the TARM on PCT maps, its relative perfusion values by
      comparison with contralateral, mirrored tissue, and its correlation with
      occurrence and final size of cerebral infarction on follow-up imaging. RESULTS:
      An ischemic area was visible in 64, 58.9 and 72.6% on the conventional CBF, CBV
      and TTP maps, respectively. After window narrowing, a TARM was present in 56.8,
      54.1 and 63.0% of slices comprising 11.9, 11.6 and 21.1% of the ipsilateral
      hemisphere (CBF, CBV and TTP), respectively. The relative perfusion values were
      38.7 (CBF) and 43.0% (CBV) for the entire ischemic area and 11.3 (CBF) and 13.3%
      (CBV) for the TARM. Definite cerebral infarction was visible on 68.1% of the
      target slices comprising 23.7 +/- 22.9% of the ipsilateral hemisphere. The size
      of the TARM correlated slightly better with the final infarction size (r=0.74
      0.82) than the entire ischemic area (r=0.61-0.79). With respect to the occurrence
      of cerebral infarction, the presence of a TARM on CBF maps showed the best
      positive (97.9%) and negative (72.7%) predictability. DISCUSSION: On PCT maps,
      window narrowing provides a standardized display of the TARM in peracute stroke.
      The severely reduced values of relative CBF and CBV suggest the TARM to indicate
      tissue most prone to infarction.

PMID- 17509231
TI  - Neuroprotective effects of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
      (Trolox), an antioxidant in middle cerebral artery occlusion induced focal
      cerebral ischemia in rats.
AB  - OBJECTIVES: In the present study, we have investigated the neuroprotective
      potential of 6hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), in
      middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia. METHODS:
      Sprague-Dawley rats were subjected to 2 hours of MCAO followed by 22 or 70 hours
      of reperfusion. After reperfusion, rats were evaluated for neurological deficits
      and cerebral infarction. Brain malondialdehyde (MDA) level and in situ terminal
      deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) were
      also estimated. RESULTS: Focal cerebral ischemia produced a significant infarct
      volume and neurological scores as compared with sham-operated animals. Cerebral
      ischemia reperfusion injury was associated with an increase in lipid peroxidation
      in ipsilateral and contralateral hemisphere of brain along with an increase in
      TUNEL positive cells in ipsilateral hemisphere of brain sections indicating
      oxidative stress and DNA fragmentation, respectively. Trolox (10 and 30 mg/kg,
      i.p.) treatment significantly decreased neurological damage which was evident
      from the reduction in infarct volume and neurological score. Trolox (30 mg/kg)
      also attenuated oxidative stress and DNA fragmentation. DISCUSSION: Oxidative
      stress-induced neuronal damage is implicated in the pathophysiology of cerebral
      ischemia. Our study suggests that Trolox is a potent neuroprotective agent in
      focal cerebral ischemia and its neuroprotective effects may be attributed to the
      reduction of lipid peroxidation and DNA fragmentation.

PMID- 17509232
TI  - Transient ischemia-induced changes of excitatory amino acid carrier 1 in the
      ventral horn of the lumbar spinal cord in rabbits.
AB  - OBJECTIVES: To examine temporal changes of EAAC1 immunoreactivity and its protein
      level in the spinal ventral horn after transient ischemia in the rabbit to
      investigate the correlation between neuronal cell death and EAAC1 in the ventral
      horn of spinal cord. METHODS: White rabbits weighing 2.5-3.0 kg were anesthetized
      with a mixture of 2.5% isoflurane in 30% oxygen and 70% nitrous oxide, and the
      abdominal aortic artery below the left renal artery was occluded for 15 minutes.
      At designated times after reperfusion, the immunohistochemical and Western blot
      analysis for EAAC1 was conducted using tissues of the seventh lumbar spinal
      segment. RESULTS: EAAC1 immunoreactivity was detected in the neurons of the
      normal spinal cord. EAAC1 immunoreactivity and protein level reduced
      significantly 30 minutes after ischemia/reperfusion, but EAAC1 immunoreactivity
      and protein level again increased by 80% versus sham 3 hours after ischemia. At
      this time point, neurological defect in hindlimb was also detected. Thereafter,
      EAAC1 immunoreactivity and protein levels remained to be attenuated in the
      ventral horn of spinal cord until 48 hours after ischemia. CONCLUSION: The
      significant change in EAAC1 expression and motor defects at early time after
      transient spinal cord ischemia relates to the acute events following
      ischemia/reperfusion. These results indicate that EAAC1 has an important role in
      the modulation of glutamate homeostasis in ischemic neurons in the spinal ventral
      horn.

PMID- 17509233
TI  - Do sodium channel blockers have neuroprotective effect after onset of ischemic
      insult?
AB  - OBJECTIVE: Cerebral ischemia causes a series of pathophysiologic events that may
      result in cerebral infarct. Some neurons are more vulnerable to ischemia,
      particularly pyramidal neurons in the hippocampal CA1 region. Pharmacologic
      intervention for treatment of cerebral ischemia aims to counteract secondary
      neurotoxic events or to interrupt the progression of this process. In the present
      study, we compare the neuroprotective effects of sodium channel blockers
      (mexiletine, riluzole and phenytoin) and investigate whether they have
      neuroprotective effect when given after ischemic insult. METHODS: A transient
      global cerebral ischemia model was performed in this study by clipping bilateral
      common carotid arteries during 45 minutes. Riluzole (8 mg/kg), mexiletine (80
      mg/kg) and phenytoin (200 mg/kg) were injected into the rats intraperitoneally 30
      minutes before or after reperfusion. Lipid peroxidation levels and cerebral water
      contents were evaluated 24 hours after ischemia. Histopathologic assessment of
      hippocampal region was determined 7 days after ischemia. RESULTS: Riluzole,
      mexiletine and phenytoin treatment after global ischemia significantly decreased
      water content of the ischemic brain (p<0.05 for each). No significant difference
      was observed in cerebral edema among the drug treatment groups (p>0.05). When pre
      treatment and post-treatment groups were compared with each other, only riluzole
      pre-treatment group revealed better result for cerebral edema (p<0.05). Pre
      treatment with these drugs revealed significantly better results for the
      malonyldialdehyde (MDA) level and the number of survival neuron on the
      hippocampal region than the post-treatment groups. CONCLUSION: It is demonstrated
      that riluzole, mexiletine and phenytoin are potent neuroprotective agents in the
      rat model of transient global cerebral ischemia, but they are more effective when
      given before onset of the ischemia.

PMID- 17509234
TI  - Solid lipid nanoparticles: could they help to improve the efficacy of
      pharmacologic treatments for brain tumors?
AB  - OBJECTIVES: Brain malignant neoplasms are still characterized by poor prognosis
      due to their peculiar hallmarks that severely limit aggressive multimodal
      therapeutic approaches. The optimization of the intratumoral drug delivery,
      directed to achieve effective concentrations and to reduce systemic undesired
      toxicity, is one of the primary goals of the brain tumors therapeutic strategies.
      Different passive and active delivery carriers allowing to a better control of
      drug distribution, metabolism, and elimination after parenteral administration
      have been developed. In the present review we will describe general
      characteristics and evaluate the efficacy of Solid Lipid Nanoparticles (SLN) as
      carriers of different drugs in experimental brain malignant tumor therapy.
      METHODS: SLN vehiculating different illustrative types of antineoplastic agents
      (conventional cytotoxic drugs such as doxorubicin and paclitaxel, the prodrug
      Cholesteryl butyrate, and anti VEGF antisense oligonucleotides) have been tested
      in experimental animal models of cerebral gliomas. RESULTS: SLN proved to
      successfully vehiculate into the brain different types of cytotoxic and gene
      therapeutical agents (otherwise unable to pass through the Blood-Brain Barrier)
      and to induce effective anti-tumoral therapeutical response. DISCUSSION: Compared
      to other vehicules, SLN seem to offer more advantages (such as higher physical
      stability, greater protection from degradation and better release profile of
      incorporated drugs, good tolerability and possibility of site-specific targeting)
      and could be regarded as an effective carrier for chemotherapeutic drugs, gene
      therapeutical agents, and diagnostic tools in neuro-oncology.

PMID- 17509235
TI  - Neuroprotective effect of dapsone in patients with acute ischemic stroke: a pilot
      study.
AB  - OBJECTIVES: In a previous study of brain ischemia in rats, dapsone (4,4'-diamino
      diphenylsulfone) was associated with a neuroprotective effect. As dapsone is safe
      and relatively free of adverse reactions, we conducted a pilot clinical trial to
      assess the possibility of using this drug in patients with a cerebral infarction.
      METHODS: A double-blind, placebo-controlled, pilot clinical trial of dapsone was
      conducted from January 1999 to January 2000. Thirty patients with a CT or MRI
      documented ischemic stroke in the territory of the middle cerebral artery were
      included. Patients with >4 points of the National Institute of Health Stroke
      Scale (NIHSS) were randomly allocated to receive either a single dose of 200 mg
      dapsone or placebo. For follow-up, NIHSS on days 0, 2, 7 and 60, modified Rankin
      scale and Barthel index at day 60 were applied. Adverse reactions were also
      recorded. The main cut point was considered when a patient obtained a variation
      of 2 points for modified Rankin scale and 17 points for Barthel index. RESULTS:
      Fifteen patients received dapsone and 15 received placebo. Twenty-nine were
      followed up for 60 days and one patient in the treatment group died during follow
      up. Favorable scores were achieved for treated patients by all different
      measures; NIHSS (p=0.032), Barthel (p=0.049) and Rankin scale (RR=0.182, 95% CI:
      0.04 and 0.86). Best results were obtained when treatment started within the
      first 8-10 hours after stroke. No adverse reactions related to medication were
      reported. DISCUSSION: Dapsone appears as a useful and safe drug for the treatment
      of stroke patients. Results of this pilot trial are promising and support further
      research to define the role of dapsone as a neuroprotective drug.

PMID- 17509237
TI  - Evaluating patients the new-fashioned way.

PMID- 17509238
TI  - The "bicameral mind" 30 years on: a critical reappraisal of Julian Jaynes'
      hypothesis.
AB  - In 1976 Julian Jaynes published his controversial book The Origins of
      Consciousness in the Breakdown of the Bicameral Mind, introducing the hypothesis
      of a two-chambered brain-mind model that preceded the evolutionary development of
      the conscious mind. Jaynes' speculative model gave rise to a huge debate, which
      has reverberated throughout the current neuroscientific and neurophilosophical
      literature. Has the bicameral mind stood the test of time? To answer this
      question, the present paper adopts a multidisciplinary perspective and, after
      briefly summarizing Jaynes' hypothesis, addresses two main critical issues: the
      neurological basis of the bicameral model and the philological accuracy of
      Jaynes' arguments. Finally, the concept of a non-unitary Self is presented as one
      of the most relevant contemporary legacies of the bicameral mind.

PMID- 17509239
TI  - Analysis of the correlation between three methods used in the assessment of
      children with cerebral palsy.
AB  - The primary aim of this study was to assess the correlations between gait
      analysis, magnetic resonance imaging (MRI), and Gross Motor Function Measure
      (GMFM) scores in children with cerebral palsy (CP). These common diagnostic tools
      were used to evaluate 21 children affected by CP (mean age: 6 years, range: 5-13
      years; 8 females and 13 males; 5 left hemiplegics, 4 right hemiplegics, 12
      diplegics). In particular, in order to compare gait analysis data with other
      diagnostic evaluations, the Normalcy Index (NI) was used. The results showed a
      good correlation between the NI and the results of MRI, and between NI and the
      GMFM score (r=-0.76). Therefore, this investigation demonstrated that there
      exists a strong relationship between gait analysis and other clinical evaluation
      tools.

PMID- 17509240
TI  - Are patients with hereditary spastic paraplegia different from patients with
      spastic diplegia during walking? Gait evaluation using 3D gait analysis.
AB  - Patients with hereditary spastic paraplegia (HSP) often resemble patients with
      mild spastic diplegia (SD), although their motor limitations differ. The aim of
      this study was to analyse quantitatively the gait of HSP and SD subjects in order
      to define the gait pattern in HSP and the differences between the two conditions.
      Fifteen subjects with HSP, 40 patients with SD and 20 healthy subjects underwent
      gait analysis (GA). The spatio-temporal and kinematic parameters at the proximal
      joints were found to be similar in HSP and SD, whereas the most significant
      differences were found at the knee and ankle joints. Both groups displayed a
      tendency for knee hyperextension in the midstance phase, but the duration of this
      hyperextension was longer in the HSP patients. This study shows that GA
      complements traditional clinical evaluations, making it possible to distinguish,
      clearly, between motor ability in HSP and in SD patients; the duration of the
      knee hyperextension during midstance was found to discriminate between the two
      gait patterns.

PMID- 17509241
TI  - Trials and training with 100 self-rated verbal reactions and a theory of
      sequences.
AB  - Sequences of verbal reactions, in particular 100 self-rated reactions, were
      investigated in 51 normal subjects and 61 patients with different neurological
      disorders. The non-linear course of the sequences is highlighted, and the factors
      influencing the occurrence of variations are studied. Inter-individual
      differences in the first interstimulus intervals (ISI alpha), and deviations
      between ISI alpha and subsequent interstimulus intervals, were systematically
      measured and the distribution of the results analyzed in histograms: a bimodal
      distribution was found. Cognitive styles were classified using the Big Five
      Questionnaire and Matching Familiar Figure Test: a significant correlation was
      found between impulsive and reflective subjects and the bimodal distribution of
      the interstimulus intervals. The intermediary oscillations of the temporal
      parameters of reaction sequences were systematically analyzed, and neurological
      and psychological factors influencing their occurrence identified. The issues
      arising from these studies are incorporated into a theory of sequences in
      neurophysiology. Their relevance to neurorehabilitation training processes is
      pointed out, and the advantages of paramodular tailored training of working
      memory are documented.

PMID- 17509242
TI  - Amyotrophic lateral sclerosis and prolactinoma.
AB  - A 59-year-old male with amyotrophic lateral sclerosis is presented.
      Investigations revealed the co-existence of a pituitary adenoma of the
      prolactinoma type. This combination has not been reported before. The possible
      relation between endocrinological disturbances and this neurological disease is
      discussed.

PMID- 17509243
TI  - A polynomial function of gait performance.
AB  - A mathematical data processing method is presented that represents a further step
      in gait analysis. The proposed polynomial regression analysis is reliable in
      assessing differences in the same patient and even on the same day. The program
      also calculates the confidence interval of the whole curve. The procedure was
      applied to normal subjects in order to collect normative data. When a new subject
      is tested, the polynomial function obtained is graphically superimposed on
      control data. Should the new curve fall within the limits described by normative
      data, it is considered to be equivalent. The procedure can be applied to the same
      subject, either normal or pathological, for retesting kinematic characteristics.
      The gait cycle is analyzed as a whole, not point-by-point. Ten normal subjects
      and two patients, one with recent- and the other with late-onset hemiplegia, were
      tested. Multiple baseline evaluation is recommended before the start of a
      rehabilitation program.

PMID- 17509244
TI  - The Italian version of the Coma Recovery Scale-Revised (CRS-R).
AB  - We present, in the appendix, the Italian version of the Coma Recovery Scale
      Revised (CRS-R), a reliable tool that can distinguish patients in the minimally
      conscious state from those in a vegetative state. The CRS-R consists of 29
      hierarchically organised items divided into 6 subscales addressing auditory,
      visual, motor, oromotor, communication, and arousal processes. The translation
      procedure, designed to ensure the development of an Italian version of the CRS-R
      that mirrors the structure and content of the original, was the following: three
      translations of the scale were concurrently completed by authors from the groups
      involved in the study; a selected version underwent back translation to detect
      errors in translation and to ensure that there was no misinterpretation of
      administration and scoring guidelines; a consensus meeting was held to agree on a
      fully comprehensible and accurate Italian translation that was consistent with
      the original English text; the authors of the original version were consulted for
      additional assistance with translation when consensus could not be reached; a
      final back translation was done based on the agreed Italian version. The Italian
      version of the scale is now available for use in clinical practice and in studies
      designed to investigate its psychometric properties; this will help in the
      coordination of multicentre studies to assess its reliability.

PMID- 17509245
TI  - Lessons from the past: failed MS trials.

PMID- 17509246
TI  - Early MS treatment.
AB  - Evidence from research suggests that many patients with clinically isolated
      syndromes or early MS should be treated with disease-modifying drugs at an early
      stage. Certainly, when continuing disease activity has been demonstrated
      clinically or by magnetic resonance imaging (MRI), the need to initiate treatment
      is clear. Studies supporting early treatment rely on evidence which shows that
      the experiences of the first few years are likely to impact on the long-term
      evolution of the disease. The decision to start treatment should be made jointly
      by the patient and the physician after reviewing the existing evidence. While MRI
      can be used to determine who will benefit most from treatment, the use of other
      biological markers needs to be confirmed in different settings before they can be
      used in clinical practice.

PMID- 17509247
TI  - 22nd ECTRIMS Congress, Madrid, Spain, 27,30 September 2006.

PMID- 17509248
TI  - Magnetic resonance imaging of grey matter damage in people with MS.
AB  - The classical view of MS as an inflammatory-demyelinating condition affecting the
      white matter (WM) of the central nervous system (CNS) has recently been
      challenged by the results of several magnetic resonance imaging (MRI) studies.
      These consistently show grey matter (GM) involvement, which correlates only
      moderately with the extent of WM pathology. Here we summarize how conventional
      and modern imaging-based techniques have quantified GM damage in MS, in terms of
      focal lesions, diffuse tissue abnormalities and irreversible tissue loss. Results
      from functional MRI studies, together with these new findings, are contributing
      to a significant change in our MS understanding. MS is now viewed as a global CNS
      condition, affecting both WM and GM, which has an early and important
      neurodegenerative component.

PMID- 17509249
TI  - What is new in symptom management?
AB  - Many people with MS suffer from severe and disabling symptoms that restrict their
      social and private lives, and hence affect their quality of life; it is,
      therefore, essential that any symptoms that they experience are reduced
      effectively. Symptomatic treatment should also aim to prevent secondary
      complications that may result from existing disabilities. Since many MS patients
      are unaware that some of their complaints may be attributable to MS, e.g.
      fatigue, sexual dysfunction, pain or dysphagia, all patients should be thoroughly
      questioned about all healthcare issues and the results must be documented. In
      recent months, several studies about the treatment of important MS symptoms--like
      spasticity, pain, fatigue, bladder and sexual dysfunction, depression and
      cognitive impairment--have been published; this article will briefly summarize
      and discuss some of these treatments.

PMID- 17509250
TI  - European Charcot Foundation Symposium, Taormina, Sicily, Italy, 16,18 November
      2006.

PMID- 17509251
TI  - Diagnosing MS: recent guidelines and future goals focusing on magnetic resonance
      imaging.
AB  - Previous diagnostic guidelines for MS relied largely on clinical evidence and
      cerebrospinal fluid analysis. In 2001, guidelines were published that allowed
      partial substitution of the required clinical evidence by magnetic resonance
      imaging findings and defined primary progressive multiple sclerosis (PPMS).
      Recently, revised guidelines on MS diagnosis were published, mainly to improve
      definitions of dissemination in space (using spinal cord imaging) and in time
      (using T2 lesions), enabling a faster and more accurate MS diagnosis. Criteria
      for PPMS were also revised. Current research is concentrating on the definition
      of uniform clinical terms, to allow a more standardized diagnosis, and aims to
      simplify the criteria while improving diagnostic accuracy.

PMID- 17509252
TI  - Chronic myelogenous leukemia.

PMID- 17509253
TI  - Monitoring chronic myelogenous leukemia in the age of tyrosine kinase inhibitors.
AB  - Tyrosine kinase inhibitors (TKIs) are now standard up-front therapy for chronic
      myeloid leukemia (CML). Patients with newly diagnosed chronic-phase CML treated
      with the TKI imatinib mesylate typically experience a complete cytogenetic
      remission. Outcomes for patients with advanced-phase disease are distinctly
      worse. Unfortunately, a small proportion of chronic-phase patients experience
      relapse during this therapy, and most with advanced-phase disease develop
      resistance to imatinib mesylate after months of therapy. Hematopoietic cell
      transplantation remains the only curative approach for CML and can salvage
      patients with advanced-phase disease. Therefore, physicians must carefully
      monitor patients with chronic-phase CML treated with TKIs so that they can
      undergo hematopoietic cell transplant (or treatment with another TKI or
      experimental therapy) before frank progression occurs. Fortunately, monitoring
      CML using cytogenetic and molecular methods (i.e., quantitative polymerase chain
      reaction) effectively defines end points that correlate highly with outcome.

PMID- 17509254
TI  - Basal cell and squamous cell skin cancers.

PMID- 17509255
TI  - Photodynamic therapy for non-melanoma skin cancer.
AB  - Photodynamic therapy (PDT) involves the administration of a photosensitizing drug
      and its subsequent activation by light at wavelengths matching the absorption
      spectrum of the photosensitizer. Because the skin is readily accessible to light
      based therapies, PDT with systemic and particularly with topical agents has
      become important in treating cutaneous disorders. Topical PDT is indicated for
      treating actinic keratosis, superficial or thin non-melanoma skin cancer,
      including some cases of nodular basal cell carcinoma, and some cutaneous
      lymphomas. Advantages of aminolevulinic acid/methyl aminolevulinate PDT include
      the possibility of simultaneous treatment of multiple tumors and large surface
      areas, good cosmesis, and minimal morbidity, such as bleeding, scarring, or
      infection.

PMID- 17509256
TI  - Transplant-associated skin cancer: role of reducing immunosuppression.
AB  - This article explores the role of reducing immunosuppression as a therapeutic
      strategy for the problem of transplant-associated skin cancer. The specific issue
      of immunosuppression reduction is based on a brief historic review of the
      epidemiology of skin cancer in transplant patients, followed by a description of
      the role of immunosuppression as a cause of skin cancer. Finally, the literature
      pertaining to the hypothesis that reducing immunosuppression in solid organ
      transplant recipients favorably impacts both the incidence of cutaneous
      malignancy and outcomes relating to individual aggressive malignancies is
      presented.

PMID- 17509257
TI  - Dermatofibrosarcoma protuberans.

PMID- 17509258
TI  - Molecular targeting of dermatofibrosarcoma protuberans: a new approach to a
      surgical disease.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignancy of the skin and
      subcutaneous tissues that only rarely forms distant metastases. More than 90% of
      cases are associated with a chromosomal translocation involving the COL1A1 gene
      on chromosome 17 and the platelet-derived growth factor B gene on chromosome 22.
      Management of this disease is primarily surgical with excellent rates of local
      control obtained using either wide local excision or Mohs micrographic surgery.
      Data have recently shown that inhibiting platelet-derived growth factor receptors
      (PDGFR) with imatinib can induce high rates of clinical response in patients with
      unresectable or metastatic DFSP. These data have led to approval of imatinib by
      the U.S. Food and Drug Administration for treating uresectable DFSP. Although
      wide surgical excision remains standard care, patients with locally advanced
      disease not suitable for surgical excision can be treated with the PDGFR
      inhibitor imatinib, which sometimes allows residual DFSP to be surgically
      excised.

PMID- 17509259
TI  - NCCN task force report: positron emission tomography (PET)/computed tomography
      (CT) scanning in cancer.
AB  - The use of positron emission tomography (PET) is increasing rapidly in the United
      States, with the most common use of PET scanning related to oncology. It is
      especially useful in the staging and management of lymphoma, lung cancer, and
      colorectal cancer, according to a panel of expert radiologists, surgeons,
      radiation oncologists, nuclear medicine physicians, medical oncologists, and
      general internists convened in November 2006 by the National Comprehensive Cancer
      Network. The Task Force was charged with reviewing existing data and developing
      clinical recommendations for the use of PET scans in the evaluation and
      management of breast cancer, colon cancer, non-small cell lung cancer, and
      lymphoma. This report summarizes the proceedings of this meeting, including
      discussions of the background of PET, possible future developments, and the role
      of PET in oncology.

PMID- 17509260
TI  - Classification of femoral periprosthetic fractures.
AB  - Classification systems for fractures of the femur with a prosthetic hip in situ
      are diverse and complex. Most of them are based on the site of the fracture,
      which is not the most important differentiating factor in treatment planning. The
      Coventry classification system groups the periprosthetic fractures into 'happy
      hips' and 'unhappy hips' based on whether or not the stem is loose. In 'happy'
      hips, treatment only needs to address the fracture itself, unless the fixation
      has been compromised by the fracture. In the 'unhappy hips', revision of the
      prosthesis is recommended.

PMID- 17509261
TI  - Lipopolysaccharide up-regulates heat shock protein expression in rat lung
      pericytes.
AB  - BACKGROUND: Heat shock proteins (HSP) function as molecular chaperones,
      participating in protein folding and maturation throughout the cell. Serum HSPs
      may correlate with acute lung injury. Pericytes are perivascular cells located
      abluminally from endothelial cells, and play a regulatory role in capillary leak.
      It is our hypothesis that pericytes express HSP 60 and HSP 70, and these HSPs are
      up-regulated in response to lipopolysaccharide (LPS). METHODS: Rat microvascular
      lung pericytes were isolated and cultured. Cells from passages three to five were
      used and treated with LPS (control, 10 ng/mL, and 100 ng/mL) for either 4 or 18
      h. Immunoblotting and real-time PCR were used to analyze the presence and
      quantity of HSP 60 and HSP 70. RESULTS: Immunoblotting revealed the presence of
      HSP 60 and HSP 70 in control pericytes. After 4 h of treatment with LPS (10 ng/mL
      and 100 ng/mL), no increase in protein expression of HSP 60 or HSP 70 was seen.
      However, after 18 h an increase in protein expression of HSP 60 and HSP 70 was
      seen. Real-time PCR demonstrated the presence of HSP 60 mRNA and HSP 70 mRNA in
      control pericytes. An increase in mRNA was seen after 18 h of LPS treatment, but
      not after 4 h. CONCLUSIONS: This study provides the first in vitro evidence that
      rat lung pericytes express HSP 60 and HSP 70. HSP 60 and HSP 70 are up-regulated
      after 18 h of LPS exposure. Pericyte heat shock protein expression may contribute
      to the lung's response seen in sepsis.

PMID- 17509262
TI  - Enhancing the mission of academic surgery by promoting scientific writing skills.
AB  - Writing and publishing are key to career development and academic success for
      surgeons who have less time than ever to devote to these activities. To improve
      the scientific writing skills of its faculty and trainees and to help them
      complete their manuscripts and grant proposals more quickly, the Department of
      Surgery at the University of California, San Francisco (UCSF) established a
      service dedicated to scientific writing and editing. Through coursework in
      scientific writing, individual writing consultations, and editorial review, the
      service helps academic surgeons with the difficult tasks of writing and
      publishing their research and seeking extramural funding. The service has rapidly
      become a successful adjunct to the academic mission of the UCSF Department of
      Surgery and could offer a model for other academic surgery departments to
      increase scientific productivity and advance the academic surgical mission.

PMID- 17509263
TI  - Gastrointestinal monitor: automatic titration of jejunal inflow to match
      peristaltic outflow.
AB  - A peristaltic gradient insures that chyme normally removed from the jejunal
      feeding site continues to be propelled caudad. The trigger for iatrogenic
      "feeding intolerance" is the inadvertently overwhelming of the jejunum's
      peristaltic outflow, even momentarily. Even minimum local stasis can stimulate a
      vagal reflex response. Motility of the sluggish gut further slows, leading to
      generalized abdominal distention, malaise, immobility, and impaired respiratory
      mechanics. Vagal vascular reflexes could explain the 1:1000 incidence of bowel
      necrosis for jejunally fed patients. We developed a clinical regimen that
      continuously "checks for residual" at the enteral feeding site, monitoring the
      adequacy of emptying. The jejunal inflow automatically is titrated to match
      peristaltic outflow if the latter cannot keep up. Intermittent suction aspirates
      the feeding catheter into a plastic chamber for 30 s. All swallowed air is
      removed efficiently within the close confines of the jejunal segment, without
      wasting digestive juices. The degassed aspirate is returned by gravity with the
      feedings during the second half of the 1-min cycle, unless incipient excess
      (>or=20 mL) fluid overflows. Only this relatively small volume of potentially
      excess fluid is discarded, forestalling the local distention. All patients
      tolerated immediate feeding without discomfort or abdominal distention, including
      three that had esophageal resection (including vagotomy) for carcinoma.
      Postoperative full enteral nutrition can be achieved quickly and safely with
      minimum attention, despite initially marginal gastrointestinal function.

PMID- 17509264
TI  - Parathyroidectomy for primary hyperparathyroidism in octogenarians and
      nonagenarians: a risk-benefit analysis.
AB  - BACKGROUND: The only cure for primary hyperparathyroidism (1 degrees HPT) is
      parathyroidectomy. However, many elderly patients are not referred for surgery
      due to medical comorbidities and/or advanced age. The purpose of this study was
      to evaluate benefits against risks of parathyroidectomy in this patient
      population. MATERIALS AND METHODS: From March 2001 to June 2006, 50 patients aged
      80 years or older with 1 degrees HPT underwent parathyroidectomy by a single
      surgeon. Clinical presentation and surgical outcomes of all patients were
      evaluated. The standard form of the SF-36 Health Survey, designed to measure
      patient quality of life (QOL), was completed by a subset of patients. RESULTS:
      There were 45 females and 5 males with a mean age of 83 +/- 2 y. Patient
      comorbidities included hypertension (72%), coronary artery disease (22%),
      diabetes mellitus (16%), chronic obstructive pulmonary disease (10%), and
      congestive heart failure (10%). Bone pain was the most common primary presenting
      symptom (44%), followed by fatigue (12%), confusion (6%), and joint pain (6%).
      Eleven patients (22%) had ectopic glands. The cure rate postsurgery was 98%
      (49/50). There were 2 postoperative complications (4%): one patient with
      transient hypocalcemia and another with cellulitus at an i.v. site. Of patients
      who completed QOL surveys, greater than 60% reported improved physical
      functioning, social functioning, and/or mental health, and reduction of bodily
      pain. CONCLUSION: Parathyroidectomy is safe and curative for octogenarians and
      nonagenarians with 1 degrees HPT, and maintains or improves quality of life. The
      surgical benefits outweigh operative risks, making parathyroid surgery an
      excellent option for patients over 80 years of age.

PMID- 17509265
TI  - Preclinical predictors of surgery NBME exam performance.
AB  - BACKGROUND: The passing score for the National Board of Medical Examiner's
      Surgery Subject Examination (NBME-SS) was raised at an urban academic medical
      school, resulting in a doubling of the number of students failing their surgical
      clerkship. We hypothesized that at-risk students could be accurately identified
      and offered an intense tutorial program to enhance success on their exam.
      METHODS: Preclinical academic records for the graduating class of 2006 were
      obtained and included gender, ethnicity, preclinical grades, and preclinical
      NBME's exams, MCAT, and USMLE scores. Simple and multiple linear regression
      analyses were used to identify correlates with the surgery shelf exam scores and
      data from the class of 2007 were used for validation. RESULTS: Data were
      collected on 194 students. On univariate analysis, MCAT, USMLE, and all
      individual preclinical NBME scores were positively correlated with the NBME-SS
      (P<0.05). Variables that remained predictive using multiple linear regression
      were scores on the pathology and physical diagnosis exams (model r(2)=0.48). The
      single strongest predictor of failure was performance on the pathology shelf exam
      (ROC area was 0.85 with P<0.0001), which also held true for the class of 2007.
      CONCLUSIONS: There is a strong correlation between poor performance on the third
      year NBME-SS and the second-year pathology NBME scores. The reason for this
      correlation is unclear but may be related to the integrative thinking and
      clinical application skills requisite for surgical decision-making first required
      by preclinical students during their pathology course. Whether efforts to assist
      medical students with this skill set will be effective warrants further study.

PMID- 17509266
TI  - Can screening items identify surgery patients at risk of limited health literacy?
AB  - BACKGROUND: Health literacy skills (HLS) have been shown to have a major impact
      on patient outcomes. To identify patients with limited or marginal HLS, the
      accuracy of three established screening items were examined. MATERIALS AND
      METHODS: We studied English-speaking adults (>or=21 years) attending a university
      based vascular surgery clinic. Structured interviews were conducted to assess
      sociodemographic characteristics, screening items, and HLS. Area under the
      receiver operating characteristic (AUROC) curves were plotted to assess the
      discriminatory capacity of each screening item in detecting patients with
      limited/marginal HLS. RESULTS: One hundred patients agreed to enter the study and
      met inclusion criteria. The mean age was 62.0 +/- 12.9; 65 were female; 96 were
      Caucasian; and 32 had not completed high school. The three screening items were
      effective in detecting patients with limited (n=18) or marginal (n=21) HLS. "How
      often do you have someone (like a family member, friend, or hospital worker) help
      you read hospital materials?" (AUROC of 0.83; 95% confidence interval [CI]=0.73,
      0.92), "How often do you have problems learning about your medical condition
      because of difficulty understanding written information?" (AUROC of 0.77; 95%
      CI=0.67, 0.86), and "How confident are you filling out medical forms by
      yourself?" (AUROC of 0.76; 95% CI=0.66, 0.86) were effective in detecting those
      with limited/marginal HLS skills. CONCLUSIONS: Our findings provide further
      evidence of the clinical usefulness of these screening items for detecting
      inadequate HLS in this patient population. Surgeons should consider administering
      these easy screening items to identify patients at greatest risk of limited or
      marginal HLS.

PMID- 17509267
TI  - Effect of intraoperative hyperglycemia during liver transplantation.
AB  - BACKGROUND: Intensive blood glucose management has been shown to decrease
      mortality and infections for intensive care patients. The effect of
      intraoperative strict glucose control on surgical outcomes, including liver
      transplantation, has not been well evaluated. MATERIALS AND METHODS: A
      retrospective review of all adult liver recipients transplanted between January
      1, 2004 and July 6, 2006 was performed. Donor and recipient demographics,
      intraoperative variables, and outcomes were collected. Intraoperative glucose
      measurements were performed by the anesthesiology team and treated with
      intravenous insulin bolus or continuous infusion. Patients with strict glycemic
      control (mean blood glucose <150 mg/dL) were compared with those with poor
      control (mean blood glucose >or=150 mg/dL). RESULTS: During the study period, a
      total of 184 patients met criteria for analysis. Recipients with strict glycemic
      control (n=60) had a mean glucose of 135 mg/dL compared with 184 mg/dL in the
      poorly controlled group (n=124). Other than recipient age (strict versus poor
      control, 47 +/- 2 y versus 53 +/- 1 y; P<0.01), both groups had similar donor and
      recipient characteristics. Although the incidence of most postoperative
      complications were similar, poor glycemic control was associated with a
      significantly increased infection rate at 30 d posttransplant (48% versus 30%;
      P=0.02), and also an increased 1 y mortality (21.9% versus 8.8%; P=0.05).
      CONCLUSIONS: Intraoperative hyperglycemia during liver transplantation was
      associated with an increased risk of postoperative infection and mortality.
      Strict intraoperative glycemic control, possibly using insulin infusions, may
      improve outcomes following liver transplantation.

PMID- 17509268
TI  - Abdominal complications related to type of repair for congenital diaphragmatic
      hernia.
AB  - BACKGROUND: Literature on congenital diaphragmatic hernia (CDH) over the past few
      decades has focused on prognostic factors and management of pulmonary
      hypertension/hypoplasia. Larger diaphragmatic defects may require patch closure,
      reported by some authors to be associated with poorer outcomes. In this study, we
      evaluate the impact synthetic material has on the need for subsequent abdominal
      operations, particularly recurrence and small bowel obstruction (SBO). METHODS:
      After obtaining IRB approval, all patients undergoing repair of congenital
      diaphragmatic from January, 1994 to December, 2004 were investigated. Records
      from primary and subsequent admissions were reviewed to identify those patients
      who underwent major procedures after repair of the diaphragmatic defect.
      Subsequent abdominal operations in these series were recurrent CDH repair,
      exploration for SBO and fundoplication. Patients who died prior to hospital
      discharge were excluded. Statistical comparisons were made using Fisher's exact
      test: significance was defined as P<0.05. RESULTS: During the study period, there
      were 81 survivors from CDH repair, 24 with a synthetic patch, and 57 without.
      Those with a patch repair had a significantly increased risk of recurrence, small
      bowel obstruction, and subsequent operation (Table 1). Eleven patients had
      nonabsorbable mesh patches, and 13 were repaired with absorbable (Surgisis-Gold;
      Cook Technology Inc., West Lafayette, IN). While there were no differences in
      recurrence between these two groups, four patients (31%) with Surgisis developed
      SBO compared with one patient (9%) repaired with a nonabsorbable synthetic.
      CONCLUSIONS: Incidence of SBO and recurrent CDH in patients with a patch was
      higher than those who underwent primary repair. There may also be a difference in
      the rate of subsequent SBO depending on the type of mesh used. A prospective
      trial is under way at our institution to help define this issue.

PMID- 17509269
TI  - Postoperative pericardial adhesion prevention using Carbylan-SX in a rabbit
      model.
AB  - INTRODUCTION: The presence of dense adhesions within the pericardial space
      complicates reoperative cardiac surgery. Prior attempts to reduce adhesion
      formation after primary cardiac surgery using medications or biomaterials have
      had variable success. Carbylan-SX (Carbylan Biosurgery Inc., Palo Alto, CA) is a
      hyaluronan-based biomaterial, which has been shown to be effective at reducing
      adhesions in a nonthoracic rat model. This study evaluates whether Carbylan-SX
      can effectively reduce postoperative adhesions within the pericardial cavity.
      METHODS: Thirty-eight New Zealand white rabbits underwent a left lateral
      thoracotomy. A pericardiotomy was made and epicardial adhesions were induced on
      the anterior surface of the heart using a Dremel device (Racine, WI). The rabbits
      were divided into four groups: controls with abrasions only receiving no
      treatment (n=10), Carbylan-SX films (n=10), Carbylan-SX aerosolized hydrogel
      (n=10), and Seprafilm (n=8). The pericardial sac and chest were subsequently
      closed. Rabbits were sacrificed at a mean of 15 days. For histological analysis,
      each heart was divided into 12 separate 1 mm sections. Computer imaging software
      was used to measure the adhesion thickness and the mean of 12 random measurements
      for each animal was recorded and statistical analysis performed. RESULTS:
      Histological analysis revealed all treatment groups to be significantly better
      than the control (2159 mum thickness, P<0.0001) at preventing adhesions. The
      Carbylan-SX film and Carbylan-SX aerosolized hydrogel both proved to be better at
      preventing adhesions than Seprafilm (Genzyme Corp., Cambridge, MA) with an
      average adhesion thickness of 454 and 577 microm, respectively, compared with
      1319 microm for Seprafilm (P<0.0001 and P<0.0005, respectively). The Carbylan-SX
      film and Carbylan-SX aerosolized hydrogel were equally effective at preventing
      adhesion formation. CONCLUSION: Carbylan-SX film and Carbylan-SX aerosolized
      crosslinkable hydrogel are equally effective methods of reducing postoperative
      pericardial adhesions within the pericardial cavity. Both the Carbylan-SX film
      and aerosolized hydrogel showed a significantly greater reduction in adhesions
      than Seprafilm. Clinical application of Carbylan-SX could have significant
      therapeutic implications in the future.

PMID- 17509270
TI  - Benefits of perfusion preservation in canine hearts stored for short intervals.
AB  - BACKGROUND: Continuous perfusion of donor hearts for transplantation has been
      proposed to improve graft function or extend preservation intervals, but the
      effects on cellular metabolism, myocyte loss, and myocardial edema are not well
      defined. METHODS: Hearts from mongrel dogs were instrumented with sonomicrometry
      crystals and left ventricular (LV) catheters. LV function was quantified by the
      preload-recruitable stroke work (PRSW) relationship. Hearts were arrested with a
      modified Celsior solution, and stored in cold solution (n=6) or placed in a
      device providing continuous perfusion of this solution at 10 mL/100 g/min (n=6).
      After 4 h of storage, left atrial samples were frozen, extracted, and analyzed by
      magnetic resonance spectroscopy (MRS). Hearts were then transplanted into
      recipient dogs and reperfused for 6 h with function measured hourly. At end
      experiment, LV specimens were assayed for water content and apoptosis. Serum CK
      MB levels were measured. RESULTS: LV functional recovery was excellent in both
      groups over 6 h of reperfusion. MRS revealed a dramatic decrease in tissue
      lactate in hearts protected with continuous perfusion (P<0.01). Apoptotic cell
      counts were significantly lower in post-reperfusion heart tissue in animals
      undergoing a continuous perfusion strategy (P<0.01). CK-MB levels and LV water
      content were similar in both groups. CONCLUSIONS: Although both methods of
      preservation lead to good early graft function after 4 h of protected ischemia,
      continuous preservation dramatically reduces tissue lactate accumulation without
      increasing myocardial edema and may reduce tissue damage during storage and
      reperfusion. It appears promising as a method to improve results of cardiac
      transplantation.

PMID- 17509275
TI  - Optimizing prostate biopsy techniques.

PMID- 17509276
TI  - The evolving role of surgery for advanced renal cell carcinoma in the era of
      molecular targeted therapy.
AB  - PURPOSE: Thoughtful integration of surgical and medical approaches to metastatic
      renal cell carcinoma is paramount for maximizing disease control. Accomplishing
      this in the current era of targeted molecular therapies presents unique
      challenges and opportunities. MATERIALS AND METHODS: A systematic review of the
      MEDLINE and PubMed databases, and relevant urological and oncological journals
      was performed pertaining to cytoreductive nephrectomy, metastasectomy, targeted
      molecular therapies for renal cell carcinoma, and neoadjuvant and adjuvant
      approaches to the management of advanced renal cell carcinoma. RESULTS:
      Cytoreductive nephrectomy provides an overall survival advantage in select
      patients with metastatic renal cell carcinoma who receive subsequent interferon
      alpha. However, cytokine therapies are now being supplanted by targeted molecular
      approaches that block the effects of vascular endothelial growth factor and other
      molecular events. Although cytoreductive nephrectomy remains a standard of care,
      limited insight into the biological effects of nephrectomy on mechanisms such as
      immunoregulation and angiogenesis precludes definitive statements about how to
      integrate surgery and targeted agents. Ongoing investigation involving basic
      science and translational research is required to optimize the integration of
      these approaches. Adjuvant and neoadjuvant vascular endothelial growth factor
      targeted approaches to renal cell carcinoma are now also being explored and the
      unique side effects of these agents, including potential effects on wound healing
      and vascular integrity, require careful consideration. CONCLUSIONS: Integrated
      approaches involving surgery and vascular endothelial growth factor targeted
      therapies hold much promise for the management of advanced renal cell carcinoma.
      Prospective clinical testing with vigilant attention to the risk-benefit ratio
      and thoughtful evaluation of biological correlates are required to optimize these
      approaches.

PMID- 17509277
TI  - Prostate specific antigen recurrence after definitive therapy.
AB  - PURPOSE: We estimate that approximately 70,000 men yearly have prostate specific
      antigen-only recurrence after failed definitive therapy. The ideal salvage
      therapy for these men is not clear. Treatment must be individualized based on the
      patient risk of progression, the likelihood of success and the risks involved
      with the therapy. However, to do so the risks and benefits of the various options
      must be known. Therefore, we provide a comprehensive overview of the natural
      history and treatment options for men with prostate specific antigen-only
      recurrence. MATERIALS AND METHODS: A literature review and overview of prostate
      specific antigen-only recurrence after failed definitive therapy was done.
      RESULTS: The natural history after prostate specific antigen-only recurrence is
      long but variable. Median time from prostate specific antigen-only recurrence
      after radical prostatectomy to prostate cancer death exceeds 16 years, although
      some men die within 1 year after PSA recurrence. Rapid prostate specific antigen
      doubling time is the best prognostic factor for poor outcome. Salvage radiation
      therapy after radical prostatectomy results in a 45% 4-year prostate specific
      antigen response rate, although long-term outcomes appear poor. To our knowledge
      the effect on survival is not known. Salvage radical prostatectomy is rarely
      performed but in the highly selected patient it may provide some benefit. There
      are no randomized studies of early vs late hormonal therapy for men with prostate
      specific antigen-only recurrence. A retrospective study suggested delayed
      metastasis when therapy was begun early but only in men at high risk. This
      mirrors other data suggesting that men at high risk may derive significant
      benefits from early hormonal therapy, whereas men at low risk are unlikely to
      benefit and may be harmed by hormonal therapy. CONCLUSIONS: Prostate specific
      antigen-only recurrence is the most common form of advanced prostate cancer.
      Optimal salvage treatments and timing of these treatments remain controversial.

PMID- 17509278
TI  - On the importance of race, socioeconomic status and comorbidity when evaluating
      quality of life in men with prostate cancer.
AB  - PURPOSE: Clear and accurate information about health related quality of life
      outcomes for men diagnosed with prostate cancer is essential for men and their
      physicians to make appropriate care decisions. To determine the completeness and
      quality of available health related quality of life information we performed a
      review of health related quality of life studies, assessing what information was
      and was not reported. MATERIALS AND METHODS: A structured literature search
      identified 184 relevant health related quality of life studies representing
      40,931 subjects. RESULTS: More than 95% of health related quality of life studies
      did not provide key information about factors known to influence outcomes. The
      most common omissions included information about treatments received, followup,
      socioeconomic status or demographic characteristics. Most data were obtained from
      well educated, high income socioeconomic groups, who are generally quite healthy.
      More than 60% of subjects were college graduates, 85% were currently married and
      43% were currently employed. While black Americans comprised 15% of men studied
      in the 80% of studies reporting race, little information is available on Hispanic
      or Asian men. CONCLUSIONS: Most of the available prostate cancer health related
      quality of life literature does not describe or does not account for factors
      known to influence health outcomes. These omissions limit their interpretability
      for patients trying to make decisions about treatment. More attention should be
      given to fully characterizing all dimensions of care that may influence quality
      of life outcomes and evaluating health related quality of life in Asian and
      Hispanic populations. Men and physicians should exercise caution when
      interpreting results that do not fully account for multiple factors that
      influence health related quality of life.

PMID- 17509279
TI  - Injection, ligation and transplantation: the search for the glandular fountain of
      youth.
AB  - PURPOSE: During the 19th and early 20th centuries there was great interest in
      antiaging remedies. This search for the eternal fountain of youth stemmed from
      the concept of aging as a pathological condition that destroyed the body and
      mind. In addition, great emphasis was placed on the economic challenge that the
      elderly presented to society. We examine the history of antiaging therapies from
      the perfection of cell nutrition to glandular transplants. MATERIALS AND METHODS:
      A literature review was performed including direct first person sources such as
      historical documents, letters of correspondence, newspaper articles and journal
      publications. Historical texts were also consulted for accuracy. RESULTS: The
      history of antiaging medicine includes a variety of remedies. E. Metchnikoff
      advocated a diet rich in lactic acid which he thought would eradicate the body of
      intestinal putrefaction and decay. Others believed the fountain of youth lay
      within the endocrine system. C. E. Brown-Sequard linked the decrease in sexual
      function with the aging body and claimed he could restore a youthful state with
      the injection of a mixture of animal sex glands. The compound Spermine was
      subsequently marketed as an injection that promised the effects observed by Brown
      Sequard. The early 20th century was marked by a number of surgical attempts at
      the restoration of youth. L. L. Stanley reported on more than 643 inmates at the
      San Quentin prison on whom he had performed testicular transplantation. This idea
      of gland grafting gained international interest and led others such as S.
      Voronoff to experiment with the transplantation of various animal glands into
      humans. In addition to gland grafting, vasoligation was advocated by E. Steinach
      in an effort to direct sperm from the testicles back to the body. The Steinach
      operation was claimed to restore youth and vigor. Although most physicians
      directed their attention toward remedies for men, some came to advocate remedies
      for women including ovarian transplantation and radiation. CONCLUSIONS: The
      search for the glandular fountain of youth ultimately led to the discovery of
      testosterone. The modern day interest in plastic surgery, testosterone
      replacement and growth hormone injection underscores the concept of aging as a
      disease process. We have yet to determine whether aging represents physiology or
      pathology. However, it is certain that the search for the fountain of youth will
      continue.

PMID- 17509280
TI  - Kidney cancer.
AB  - PURPOSE: We quantified the burden of kidney cancer 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: The incidence
      of all stages of kidney cancer is increasing in America, particularly T1 disease.
      Rates are increasing more rapidly in the black than in the white population and
      survival is worse for black individuals at all stages of diagnosis. Total
      expenditures for kidney cancer were $401 million in 2000, representing a 46%
      increase from 1994. Approximately 85% of health care dollars spent on kidney
      cancer were for inpatient care with steady increases through the 1990s. Regarding
      treatment, more partial nephrectomies were performed in Medicare patients as the
      1990s progressed. Health Care Cost and Utilization Project data showed an
      increase in the number of inpatient hospitalizations but this trend was not seen
      in the Centers for Medicare and Medicaid Services data set. Length of stay
      decreased from 1994 to 2000 in the Health Care Cost and Utilization Project
      database. The adoption of laparoscopic techniques began to appear in the Veterans
      Affairs data set in 2001 and it increased thereafter. CONCLUSIONS: Increasing
      trends in the incidence of and costs associated with kidney cancer have been
      apparent for more than 10 years. As the population ages and the prevalence of
      risk factors such as obesity and hypertension increases, the burden of disease
      will increase significantly. Consideration should be given to expanding tumor
      registries such as Surveillance, Epidemiology and End Results. Treatment
      databases could better characterize the cost and effectiveness of treatment for
      metastatic disease and of trends in the adoption of laparoscopy.

PMID- 17509282
TI  - Prostate cancer.
AB  - PURPOSE: We quantified the burden of prostate cancer in the United States by
      identifying trends in incidence, disease presentation, survival rates and use of
      health care resources, and by estimating the economic impact of the disease.
      MATERIALS AND METHODS: The analytic methods used to generate these results were
      described previously. RESULTS: Age adjusted prostate cancer incidence rates
      peaked in 1992 at 237/100,000 men, decreased in 1995 and then increased at
      approximately 1.7% yearly through 2000, when the rate was 180/100,000. Marked
      stage migration and an improvement in 5-year overall survival were also noted.
      Age adjusted inpatient hospitalizations for prostate cancer decreased in the
      1990s from 729/100,000 population in 1992 to 309/100,000 in 2001. Considerable
      ethnic and regional variation was noted. During the same period age adjusted
      radical prostatectomy rates varied from 128/100,000 men in 1994 to 108/100,000 in
      2000. Surgery rates decreased in older men, while they increased in younger men.
      Outpatient physician office visits also varied in the 1990s with ethnic and
      regional variation again noted. Finally, the total medical expenditure for
      prostate cancer treatment was $1.3 billion in 2000, which represents a 30%
      increase over the total expenditure for 1994. CONCLUSIONS: The burden of prostate
      cancer in the United States is considerable and it appears to have markedly
      increased in the prostate specific antigen era. Further research is needed to
      determine if we are using our limited health care resources appropriately for the
      diagnosis and treatment of this common malignancy.

PMID- 17509283
TI  - Testis cancer.
AB  - PURPOSE: We quantified the burden of testis cancer in the United States by
      identifying trends in its incidence, its treatment and the use of health care
      resources to estimate the economic impact of the disease. MATERIALS AND METHODS:
      The analytical methods used to generate these results were described previously.
      RESULTS: The overall incidence of testis cancer in the United States increased
      46% between 1975 and 2001. During the same period the ratio of seminoma to
      nonseminoma increased and there were fewer men presenting with stage II and III
      tumors. Survival rates increased successively, attaining the current level of
      95.9%. Treatment patterns changed and active surveillance increased as a primary
      treatment modality. Overall hospitalization rates for men with testis cancer
      decreased from 1.8/100,000 in 1994 and 1.4/100,000 in 2000. Care for white men
      shifted to the outpatient setting, which did not occur for black men. The
      estimated annual expenditure for testis cancer for privately insured individuals
      between ages 18 and 54 years was $6,236. National estimates of annual medical
      expenditures placed the total cost of treatment at $21.8 million in 2000,
      representing an increase of 10% over the total in 1994. Of men with testis cancer
      16% missed work for treatment of the disease with an average of 8.4 total hours
      of work missed. CONCLUSIONS: The cost of testis cancer is estimated at almost
      $21.8 million annually. It appears to be increasing with time despite a shift to
      active surveillance treatments and less hospitalization.

PMID- 17509284
TI  - Interstitial cystitis and painful bladder syndrome.
AB  - PURPOSE: We quantified the burden of interstitial cystitis/painful bladder
      syndrome on the health care system in the United States. MATERIALS AND METHODS:
      The analytical methods used to generate these results were described previously.
      Interstitial cystitis was defined based on International Classification of
      Diseases, 9th revision code 595.1 (interstitial cystitis). For painful bladder
      syndrome we used the definition International Classification of Diseases, 9th
      revision code 788.41 (urinary frequency) with code 625.8 (other specified
      symptoms associated with female genital organs) or 625.9 (unspecified symptoms
      associated with female genital organs). RESULTS: Between 1992 and 2001 there was
      a 2-fold increase in the rate of hospital outpatient visits and a 3-fold increase
      in the rate of physician office visits related to interstitial cystitis. The
      annualized rate was 102 office visits per 100,000 population. Ambulatory surgery
      for interstitial cystitis decreased. A diagnosis of interstitial cystitis was
      associated with a 2-fold increase in direct medical costs. Between 1994 and 2000
      annual national expenditures for interstitial cystitis were stable at $37 million
      but annual costs for painful bladder syndrome increased from $481 million to $750
      million. CONCLUSIONS: Although interstitial cystitis accounts for a small percent
      of health care visits, its economic burden is substantial. Because of
      misdiagnosis, the true burden of interstitial cystitis/painful bladder syndrome
      on the health care system in the United States is probably underestimated in
      administrative data that rely only on physician coding to identify the disorder.
      The greatest part of the disease burden is likely not captured in this economic
      analysis.

PMID- 17509285
TI  - Prostatitis.
AB  - PURPOSE: We quantified the burden of prostatitis 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: The rate of
      national inpatient hospitalizations for a diagnosis of prostatitis decreased by
      21% between 1994 and 2000. Hospitalization rates were 2 to 2.5 times higher for
      Medicare beneficiaries with a 42% decrease between 1992 and 2001. Combined
      physician outpatient and hospital outpatient visits revealed an age adjusted,
      annualized visit rate for prostatitis of 1,798/100,000 population. More than 6%
      of visits with a primary diagnosis of prostatitis had a concomitant diagnosis of
      benign prostatic hyperplasia. The most common medications associated with any
      visits for prostatitis were quinolones (annualized rate 319/100,000 population)
      and the rate remained about the same even after visits for infectious prostatitis
      were removed from the data. The cost of prostatitis was about $84 million
      annually, exclusive of pharmaceutical spending. Of 897 privately insured men with
      a medical claim for prostatitis in 2002, 14% missed some work because of the
      condition. CONCLUSIONS: Overall spending in the United States for the diagnosis
      and management of prostatitis, exclusive of pharmaceutical spending, totaled $84
      million in 2000 and it appears to be increasing with time. Given the extensive
      gaps in our understanding of the diagnosis of and treatment for prostatitis, many
      of these expenditures may represent a waste of resources.

PMID- 17509286
TI  - Male infertility.
AB  - PURPOSE: We assessed male infertility and its treatment in the United States by
      identifying trends in the use of health care resources and estimating the
      economic impact of such care. MATERIALS AND METHODS: The analytical methods used
      to generate these results were previously described. RESULTS: Inpatient
      hospitalizations for male infertility were relatively few with an overall rate of
      0.9/100,000 population. Of these stays 55% were associated with inpatient
      management of varicocele and 749 of 797 occurred in a rural setting. Between 1994
      and 1996 there were 55,411 ambulatory surgery visits with men 25 to 34 years old
      having the highest use rate of 61/100,000. Men living in the West had the lowest
      rate of ambulatory surgical visits, which was significantly lower than that for
      men living in the Northeast and Midwest (29/100,000 vs 104/100,000 and
      72/100,000, respectively). The Veterans Affairs health system showed no
      geographic trend in infertility diagnosis and Hispanic men had the highest
      frequency of treatment for male infertility, followed by black and then white
      men. The National Survey for Ambulatory Surgery estimated that 67% of patients
      undergoing ambulatory surgery for male infertility had a diagnosis of varicocele.
      In 2000 total expenditures for treating primary male infertility were
      approximately $17 million. However, adding the cost for assisted reproduction
      technology cycles placed total cost at about $18 billion. CONCLUSIONS: Infertile
      males generally seek infertility care outside of traditional reimbursement
      patterns. For this reason obtaining accurate data regarding the costs associated
      with male fertility care has proved to be challenging. Given the expense of in
      vitro fertilization and its attendant technologies, emphasis should be placed on
      addressing the underlying causes of male infertility. Further systematic
      examination of the demographics and management of male reproductive dysfunction
      is warranted.

PMID- 17509287
TI  - Decreased complications of contemporary laparoscopic partial nephrectomy: use of
      a standardized reporting system.
AB  - PURPOSE: We report complications of laparoscopic partial nephrectomy in a
      contemporary cohort of 200 patients using a standardized complication reporting
      system. MATERIALS AND METHODS: The records of 200 consecutive patients undergoing
      laparoscopic partial nephrectomy between September 2003 and November 2005 were
      reviewed. Mean tumor size was 3 cm and mean parenchymal invasion depth was 1.8
      cm. There were 97 central tumors (48.5%) and 9 tumors (4.5%) in a solitary
      kidney. Complication severity for each patient was graded using a 5-tiered scale
      based on National Cancer Institute Common Toxicity Criteria. Statistical analysis
      was done to assess risk factors associated with complication events. RESULTS: A
      total of 35 patients (17.5%) had complications. The overall complication rate was
      19%. Of the complications 29%, 42%, 26% and 2.6% were grades I to IV,
      respectively. There were no grade V complications. Median blood loss was 150 ml.
      Hemorrhagic and urine leak complications occurred in 9 (4.5%) and 4 patients
      (2%), respectively. Conversion to open partial and laparoscopic radical
      nephrectomy was done electively in 2 (1%) and 1 patients (0.5%), respectively.
      Compared to previously reported data on the initial 200 patients in our
      laparoscopic partial nephrectomy cohort this contemporary group of 200 had
      statistically significant decreases in overall, urological and hemorrhagic
      complication rates despite an increase in tumor complexity (p = 0.02, 0.04 and
      0.04, respectively). CONCLUSIONS: Increased experience with advanced laparoscopic
      techniques has allowed a significantly decreased complication rate following
      contemporary laparoscopic partial nephrectomy, which now appears comparable to
      that of open partial nephrectomy. A standardized complication reporting system is
      advocated.

PMID- 17509289
TI  - Hereditary leiomyomatosis and renal cell cancer: a syndrome associated with an
      aggressive form of inherited renal cancer.
AB  - PURPOSE: Hereditary leiomyomatosis and renal cell cancer is a recently described
      hereditary cancer syndrome in which affected individuals are at risk for
      cutaneous and uterine leiomyomas, and kidney cancer. Our initial experience
      revealed the aggressive behavior of these renal tumors, often with early
      metastasis, despite small primary tumor size. We report the clinical
      characteristics and urological treatment of patients with hereditary
      leiomyomatosis and renal cell cancer associated renal tumors. MATERIALS AND
      METHODS: A total of 19 patients with hereditary leiomyomatosis and renal cell
      cancer associated renal tumors were evaluated. The 11 women and 8 men had a
      median age at diagnosis of 39 years (range 22 to 67), and a median clinical and
      radiological followup of 34 months (range 6 to 141). Hereditary leiomyomatosis
      and renal cell cancer manifestations in patients with renal tumors included
      cutaneous leiomyomas in 11 of 17 evaluable patients (65%) and uterine leiomyomas
      in 7 of 7 evaluable females (100%). RESULTS: Median pathological tumor size was
      7.8 cm (range 1.5 to 20). Histological subtypes were consistent with hereditary
      leiomyomatosis and renal cell cancer renal carcinoma. Four of 7 patients with 2.0
      to 6.7 cm T1 tumors had spread to regional lymph nodes or metastases at
      nephrectomy. Overall 9 of 19 patients (47%) presented with nodal or distant
      metastases. CONCLUSIONS: Renal tumors in patients with hereditary leiomyomatosis
      and renal cell cancer syndrome are significantly more aggressive than those in
      patients with other hereditary renal tumor syndromes. In contrast to other
      familial renal cancer syndromes, the observation of 3 cm or less renal tumors
      associated with hereditary leiomyomatosis and renal cell cancer is not
      recommended. Careful followup of affected and at risk individuals in families is
      necessary.

PMID- 17509291
TI  - Metachronous bilateral renal cell carcinoma: risk assessment, prognosis and
      relevance of the primary-free interval.
AB  - PURPOSE: We evaluated the prognosis, risk factors and relevance of the primary
      free interval in a large cohort with metachronous bilateral renal cell carcinoma.
      MATERIALS AND METHODS: We studied 120 patients with metachronous, bilateral renal
      cell carcinoma who were treated at 12 international academic centers. Logistic
      regression was performed to evaluate risk factors for contralateral metachronous
      renal cell carcinoma during followup. Disease specific survival was evaluated
      with univariate and multivariate analysis. RESULTS: Median age at diagnosis of
      the first and second renal cell carcinomas was 54 and 62 years, respectively. The
      most common histological subtype was bilateral clear cell renal cell carcinoma
      (89% of cases). Familial renal cell carcinoma was found in 14% of patients, von
      Hippel-Lindau disease was found in 4% and nonfamilial renal cell carcinoma was
      found in 81%. The 15-year disease specific survival rates for the first and
      second renal cell carcinomas were 66% and 44%, respectively. Logistic regression
      revealed von Hippel-Lindau disease, a family history of renal cell carcinoma,
      multifocal first renal cell carcinoma and young patient age as independent risk
      factors for contralateral renal cell carcinoma after surgery for unilateral renal
      cell carcinoma. A longer primary-free interval was associated with a better
      prognosis. When calculating disease specific survival from the diagnosis of the
      first renal cell carcinoma, the primary-free interval was an independent
      prognostic factor. CONCLUSIONS: Long-term survival rates of metachronous,
      bilateral renal cell carcinoma are moderate. von Hippel-Lindau disease, a family
      history of renal cell carcinoma, multifocal first renal cell carcinoma and young
      patient age are independent risk factors for contralateral renal cell carcinoma.
      These risk factors support close and extended abdominal surveillance following
      nephrectomy for unilateral renal cell carcinoma. Patients with a longer primary
      free interval have a more favorable prognosis.

PMID- 17509294
TI  - Upper tract urothelial recurrence following radical cystectomy for transitional
      cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year
      followup.
AB  - PURPOSE: Risk factors for upper tract recurrence following radical cystectomy for
      transitional cell carcinoma of the bladder are not yet well-defined. We reviewed
      our population of patients who underwent radical cystectomy to identify
      prognostic factors and clinical outcomes associated with upper tract recurrence.
      MATERIALS AND METHODS: From our prospective database of 1,359 patients who
      underwent radical cystectomy we identified 1,069 patients treated for
      transitional cell carcinoma of the bladder between January 1985 and December
      2001. Univariate analysis was completed to determine factors predictive of upper
      tract recurrence. RESULTS: A total of 853 men and 216 women were followed for a
      median of 10.3 years (maximum 18.5). There were 27 (2.5%) upper tract recurrences
      diagnosed at a median of 3.3 years (range 0.4 to 9.3). Only urethral tumor
      involvement was predictive of upper tract recurrence. In men superficial
      transitional cell carcinoma of the prostatic urethra was associated with an
      increased risk of upper tract recurrence compared with prostatic stromal invasion
      or absence of prostatic transitional cell carcinoma (p <0.01). In women urethral
      transitional cell carcinoma was associated with an increased risk of upper tract
      recurrence (p = 0.01). Despite routine surveillance 78% of upper tract recurrence
      was detected after development of symptoms. Median survival following upper tract
      recurrence was 1.7 years (range 0.2 to 8.8). Detection of asymptomatic upper
      tract recurrence via surveillance did not predict lower nephroureterectomy tumor
      stage, absence of lymph node metastases or improved survival. CONCLUSIONS:
      Patients with bladder cancer are at lifelong risk for late oncological recurrence
      in the upper tract urothelium. Patients with evidence of tumor involvement within
      the urethra are at highest risk. Surveillance regimens frequently fail to detect
      tumors before symptoms develop. However, radical nephroureterectomy can provide
      prolonged survival.

PMID- 17509295
TI  - Getting under the hood of the volume-outcome relationship for radical cystectomy.
AB  - PURPOSE: Hospital and surgeon volumes independently explain variations in
      outcomes for a host of surgical procedures. However, the mediators of the volume
      effect remain unclear. We assessed whether differences among hospitals could
      explain some or all of the volume effect on short-term outcomes after cystectomy
      for bladder cancer. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample
      a 20% sampling of hospital discharges in the United States and the American
      Hospital Association file we applied International Classification of Diseased,
      9th revision, clinical modification procedure codes to identify 1,847 patients
      who underwent cystectomy for bladder cancer in 2003. Multivariable mixed models
      were fit to quantify the differences in measures of hospital structure (capacity,
      staffing and health services) by hospital volume. Separate models were fit to
      determine the impact of accounting for these differences on the volume-outcome
      relationship. RESULTS: There were substantial differences in hospital structure
      according to radical cystectomy volume, including those characterizing capacity,
      staffing levels and the breadth of available health services. For example, 40.7%
      of low and 87.8% of high volume hospitals for radical cystectomy offered open
      heart surgery (OR 10.4, 95% CI 1.3-85.3). After adjusting for case mix patients
      treated at low volume centers were 3.2 times (95% CI 0.8-13.4) more likely to die
      postoperatively. Accounting for differences in hospital structure attenuated the
      volume effect by 59% (OR 1.9, 95% CI 0.4-8.6). CONCLUSIONS: Measurable
      differences in the availability and breadth of consultative, diagnostic and
      ancillary services may at least partially explain the association between
      procedure volume and short-term cystectomy outcomes.

PMID- 17509297
TI  - Guideline for the management of clinically localized prostate cancer: 2007
      update.

PMID- 17509298
TI  - Determining dosing intervals for luteinizing hormone releasing hormone agonists
      based on serum testosterone levels: a prospective study.
AB  - PURPOSE: Long acting luteinizing hormone releasing hormone agonists are the
      predominant form of androgen suppression in the treatment of prostate cancer with
      the goal of maintaining castrate levels of testosterone. Current dosing of
      luteinizing hormone releasing hormone agonists does not include monitoring the
      end organ response of serum testosterone. Recent evidence suggests standard
      dosing regimens fail to achieve castrate levels of testosterone in some patients
      while in other patients testosterone can remain at castrate levels longer than
      the manufacturer recommended dosing interval. We prospectively evaluated patients
      with prostate cancer receiving luteinizing hormone releasing hormone agonist
      hormonal therapy to determine the length of time that serum testosterone remains
      at or below castrate levels. MATERIALS AND METHODS: A 3-month dose of 22.5 mg
      leuprolide was administered to all patients as a first dose followed by a second
      dose 3 months later. Serum testosterone and prostate specific antigen were
      measured prospectively before starting hormonal therapy, after the first dose (12
      weeks) and again following the second dose (24 weeks) to assess if castrate
      levels of testosterone (50 ng/dl or less) had been reached. At 24 weeks if
      patient serum testosterone was 50 ng/dl or less, then 22.5 mg leuprolide were not
      administered, and serum testosterone and prostate specific antigen were checked
      monthly. When serum testosterone was greater than 50 ng/dl a subsequent dose of
      22.5 mg leuprolide was given. Serum testosterone and prostate specific antigen
      were then checked 3 months later and monthly thereafter until testosterone was
      greater than 50 ng/dl. Thus, the time that testosterone remained at castrate
      levels could be accurately established. RESULTS: From February 2003 to August
      2005, 42 patients were treated in this manner with a median followup of 18 months
      (range 10 to 30). Average patient age was 77 years. Median Gleason grade was 7
      (range 6 to 9). Median pretreatment prostate specific antigen was 15.1 ng/ml
      (range 0.6 to 433) and median posttreatment prostate specific antigen was 0.74
      (less than 0.1 to 120). The median dosing interval was 6 months (range 5 to 12).
      Three patients had an increase in prostate specific antigen while receiving
      treatment despite castrate levels of testosterone. No patient required more
      frequent dosing than every 5 months. CONCLUSIONS: Testosterone based luteinizing
      hormone releasing hormone agonist therapy makes empirical sense. It represents
      continuous androgen ablation based on the patient physiological end point, namely
      testosterone. Early data suggest that using serum testosterone to guide
      luteinizing hormone releasing hormone dosing is safe, efficacious and cost
      effective. By following end organ response, patients receive individualized care
      and more accurate androgen suppression therapy.

PMID- 17509300
TI  - Low dose metronomic oral cyclophosphamide for hormone resistant prostate cancer:
      a phase II study.
AB  - PURPOSE: Cyclophosphamide is a bifunctional alkylating agent long associated with
      immune activation. Continuous, uninterrupted, low (so-called metronomic) doses of
      cyclophosphamide can lead to enhanced immunity against a variety of antigens
      possibly by targeting regulatory T cells and/or tumor angiogenesis. In this study
      we tested the observations from animal models and evaluated the safety and
      efficacy of continuous low dose oral cyclophosphamide in patients with hormone
      resistant prostate cancer. MATERIALS AND METHODS: A total of 80 patients were
      recruited during a 2-year period and 58 received at least 2 cycles (8 weeks) of
      50 mg/m(2) oral cyclophosphamide to be included in the safety and intent to treat
      analysis. RESULTS: Metronomic cyclophosphamide was safe and well tolerated, and
      although lymphopenia (up to grade 3) was observed in a third of all patients,
      there were no clinical complications. The response rate was 34.5% inclusive of
      objective and prostate specific antigen (absolute reduction and reduction in
      prostate specific antigen velocity). The median duration of response was 7.5
      months (range 3 to 18). CONCLUSIONS: Oral cyclophosphamide can be used on a
      metronomic basis safely in men with hormone resistant prostate cancer. The
      efficacy, low toxicity, low cost and ease of administration of cyclophosphamide
      justifies further studies in prostate cancer in combination with other agents.

PMID- 17509302
TI  - A prospective, open label, randomized phase II trial of weekly docetaxel versus
      weekly vinorelbine as first line chemotherapy in patients with androgen
      independent prostate cancer.
AB  - PURPOSE: In previous phase I to III studies docetaxel and vinorelbine have shown
      promising activity in androgen independent prostate cancer. In the present trial
      we assessed the efficacy and tolerability of single agent low dose docetaxel vs
      vinorelbine in patients with advanced androgen independent prostate cancer.
      MATERIALS AND METHODS: A total of 40 chemotherapy naive patients with
      histologically proven androgen independent prostate cancer, adequate androgen
      ablation, and clinical and/or biochemical progression were randomly assigned to
      receive either 25 mg/m(2) docetaxel (arm A) or 25 mg/m(2) vinorelbine (arm B)
      weekly. Treatment was continued until clinical and/or biochemical progression. In
      cases of progression patients switched to the alternative treatment arm. The
      primary end point was time to disease progression. Secondary end points included
      prostate specific antigen response rates in sequential treatment, analgesic
      response and toxicity. RESULTS: The current analysis showed a doubled risk of
      progression in treatment arm B. The median time to first disease progression was
      14.5 months for arm A vs 4.4 months for arm B. The proportion of patients with a
      greater than 50% prostate specific antigen decrease on first line therapy was
      significantly higher in arm A (62.5%) compared to arm B (11.1%) (p = 0.0033).
      After progression to docetaxel second line vinorelbine yielded a greater than 50%
      prostate specific antigen response rate of 28.6% vs 62.5% for second line
      docetaxel. Clinically significant toxicity occurred more often in arm B with
      neutropenia grade 4 seen in 22% and grade 3 in 28% of patients (p = 0.0005)
      during the first treatment phase. CONCLUSIONS: While weekly application of both
      cytotoxic agents was well tolerated, this study demonstrates the superiority of
      docetaxel vs vinorelbine as monotherapy in the treatment of androgen independent
      prostate cancer.

PMID- 17509304
TI  - Phase II study of low dose and high dose conjugated estrogen for androgen
      independent prostate cancer.
AB  - PURPOSE: Although estrogens have known antitumor activity in androgen independent
      prostate cancer, the best studied agent, diethylstilbestrol, is no longer
      commercially available in the United States. We tested 2 doses of the conjugated
      estrogen Premarin(R) in patients with androgen independent prostate cancer to
      determine the efficacy and safety of this widely available medication. MATERIALS
      AND METHODS: A total of 45 patients with progressive androgen independent
      prostate cancer were randomly assigned to receive Premarin 1.25 mg once (17) or 3
      times (28) daily. Warfarin 1 mg daily was administered to all patients to
      minimize risk of thromboembolism. Low dose prophylactic breast irradiation was
      administered to most patients. RESULTS: Of the patients receiving high dose
      Premarin 25% achieved a 50% or greater reduction in prostate specific antigen. No
      patients treated with low dose Premarin reached a 50% reduction in prostate
      specific antigen. After 3 months of treatment, 11 patients (39.3%) on the high
      dose arm and 6 patients (35.3%) on the low dose arm showed no signs of
      progression. Three patients (6.7%) had a thromboembolic event. No significant
      gynecomastia was noted. A significant difference in dehydroepiandrosterone
      sulfate levels was detected between those who did and did not respond to Premarin
      (p = 0.03). CONCLUSIONS: High dose Premarin resulted in prostate specific antigen
      decreases of 50% or greater in 25% of patients with androgen independent prostate
      cancer. More than a third of patients receiving high or low dose Premarin
      maintained stable disease for at least 3 months. With concurrent warfarin 1 mg
      treatment, 6.7% experienced thromboembolic complications. Premarin 1.25 mg 3
      times daily is a reasonable therapeutic option for patients with androgen
      independent disease.

PMID- 17509305
TI  - An assessment of quality of life following radical prostatectomy, high dose
      external beam radiation therapy and brachytherapy iodine implantation as
      monotherapies for localized prostate cancer.
AB  - PURPOSE: Monotherapy with radical prostatectomy, high dose external beam
      radiotherapy or a (125)I implant is reported to produce equivalent outcomes. We
      assessed the health related quality of life associated with these 3 treatment
      approaches. MATERIALS AND METHODS: Extended Prostate Index Composite surveys were
      mailed to all 960 patients treated with a (125)I implant, high dose external beam
      radiotherapy or radical prostatectomy with or without hormonal therapy at our
      institution from 1998 to 2000. A total of 625 patients (65%) completed the
      surveys. Nerve sparing radical prostatectomy was performed when appropriate. The
      (125)I implant consisted of 145 Gy and high dose external beam radiotherapy
      consisted of 78 Gy. For urinary, rectal and sexual domains mean scores were
      calculated, compared by treatment modality and compared to normative values.
      RESULTS: A total of 234 patients with radical prostatectomy, 135 with external
      beam radiotherapy and 74 with a (125)I implant were treated with a monotherapy
      approach. Median age was 61 years in the radical prostatectomy group, 68 years in
      the high dose external beam radiotherapy group and 64 years in the (125)I implant
      group (p <0.001). Of the patients 97% [corrected] had cT1-2 disease and Gleason
      score 7 or less [corrected] Median time from treatment was 4.0 years for radical
      prostatectomy, 4.7 years for high dose external beam radiotherapy and 3.5 years
      for (125)I implantation. Radiation caused significantly worse bowel bother and
      bowel function than radical prostatectomy (p < or =0.018). Patients with high
      dose external beam radiotherapy had significantly better urinary function than
      patients with radical prostatectomy (p <0.001). While patients with radical
      prostatectomy had significantly worse urinary incontinence than those with a
      (125)I implant or high dose external beam radiotherapy (p <0.0001), patients with
      a (125)I implant had more urinary irritation than those with high dose external
      beam radiotherapy and radical prostatectomy (p <0.01 and <0.0001, respectively).
      Patients with a (125)I implant had significantly better sexual function than
      those with high dose external beam radiotherapy and radical prostatectomy (p =
      0.01 and 0.0003, respectively). CONCLUSIONS: Of patients with prostate cancer
      treated with a monotherapy approach we noted better urinary continence in those
      who underwent radiation based therapies, and better bowel function and less
      urinary irritation in those who underwent surgery. Sexual function was impaired
      across all monotherapies but higher scores were seen in men who selected
      brachytherapy.

PMID- 17509309
TI  - The prostate has secretory dysfunction for category IIIA and IIIB prostatitis.
AB  - PURPOSE: We investigated whether the prostate has secretory dysfunction for
      category IIIA and IIIB prostatitis. MATERIALS AND METHODS: Normal human prostatic
      secretions are remarkably rich in citrate, which is considered the most useful
      marker for determining prostate secretory function. It is certain that the
      prostate has secretory dysfunction for category I and II prostatitis, while it is
      not clear for category IIIA and IIIB prostatitis. To clarify this question
      expressed prostatic secretion citrate and pH were determined in 21, 25 and 25
      outpatients with category II, IIIA and IIIB prostatitis, respectively, and in 21
      normal controls without any prostatic disease. Outpatients with category II
      disease served as positive controls, while normal controls served as negative
      controls. No outpatients with category IIIA and IIIB prostatitis underwent
      treatment. RESULTS: Mean +/- SD expressed prostatic secretion citrate was 3.32 +/
      0.79, 3.41 +/- 0.88, 4.37 +/- 0.77 and 8.55 +/- 1.20 mg/ml in groups II, IIIA,
      IIIB and normal controls, respectively. Compared to normal controls expressed
      prostatic secretion citrate was significantly decreased in category II, IIIA and
      IIIB cases. Furthermore, there was no overlap of expressed prostatic secretion
      citrate values between category IIIA and IIIB cases, and the normal control
      group. CONCLUSIONS: The prostate has secretory dysfunction for category IIIA and
      IIIB prostatitis, which suggests that the prostate may be involved in category
      IIIA and IIIB prostatitis.

PMID- 17509308
TI  - Preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging
      penile cancer: results with pathological correlation.
AB  - PURPOSE: We assessed the sensitivity of preoperative lymphoscintigraphy and
      dynamic sentinel node biopsy for staging the inguinal region of patients with
      penile cancer and no palpable inguinal adenopathy. MATERIALS AND METHODS: The
      records of 31 patients with invasive penile cancer and nonpalpable (29) or
      nonsuspicious (2) inguinal lymph nodes were reviewed. Preoperatively
      lymphoscintigraphy plus dynamic sentinel node biopsy with (99m)technetium labeled
      sulfur colloid and isosulfan blue dye was performed in 21 patients and dynamic
      sentinel node biopsy alone with blue dye only was done in 10. All patients
      underwent superficial lymph node dissection regardless of preoperative
      lymphoscintigraphy or dynamic sentinel node biopsy findings to establish
      pathological nodal status. RESULTS: Six of 32 groins that showed drainage on
      preoperative lymphoscintigraphy had inguinal node metastasis, as did 1 of 10 that
      was drainage negative. The sensitivity of preoperative lymphoscintigraphy
      drainage for cancer detection was 86%. Using dynamic sentinel node biopsy with
      blue dye plus radiotracer 5 sentinel lymph nodes were positive for cancer,
      although 2 false-negative results were obtained. Thus, the sensitivity of dynamic
      sentinel node biopsy per groin for cancer detection was 71%. CONCLUSIONS: In our
      experience preoperative lymphoscintigraphy and dynamic sentinel node biopsy as
      currently performed remain insufficient for detecting occult inguinal disease.
      Superficial lymph node dissection remains the gold standard for detecting
      inguinal microscopic metastasis in select patients.

PMID- 17509311
TI  - Autonomic nervous system changes in men with chronic pelvic pain syndrome.
AB  - PURPOSE: We investigated the role of the autonomic nervous system in the chronic
      pelvic pain syndrome by studying blood pressure changes, power spectral analysis
      of heart rate variability, and hand and foot sympathetic skin responses in men
      with the chronic pelvic pain syndrome and healthy controls. MATERIALS AND
      METHODS: We recruited 22 men with the chronic pelvic pain syndrome and 20
      controls. The subjects underwent 5-minute resting and standing blood pressure
      readings as well as electrocardiogram recordings. Heart rate variability was
      evaluated using the low frequency (sympathetic) and high frequency
      (parasympathetic) components of power spectral analysis. We recorded sympathetic
      skin responses with surface electrodes placed on the dorsal and ventral sides of
      both hands and feet, measuring amplitude and latency. RESULTS: Mean blood
      pressure readings for supine and standing were higher in the chronic pelvic pain
      syndrome group. Between group comparisons revealed no differences in low or high
      power spectra for supine or standing positions. When subjects were taken to
      standing from the supine position, mean low frequency power increased in the
      controls and decreased in the chronic pelvic pain syndrome group. High frequency
      power, a reflection of parasympathetic activity, decreased significantly in the
      control group while the decrease was not statistically significant in the chronic
      pelvic pain syndrome group. There was no difference between the 2 groups for hand
      and foot sympathetic skin response latency and amplitudes. CONCLUSIONS: The heart
      rate variability and blood pressure changes suggest altered autonomic nervous
      system responses in men with the chronic pelvic pain syndrome. Sympathetic skin
      response findings were not conclusive. Heart rate variability and blood pressure
      findings provide a basis for therapeutic manipulation of the autonomic nervous
      system for management of the chronic pelvic pain syndrome.

PMID- 17509313
TI  - Reduction of renal stone risk by potassium-magnesium citrate during 5 weeks of
      bed rest.
AB  - PURPOSE: Exposure to the microgravity environment of space increases the risk of
      kidney stone formation, particularly for calcium oxalate and uric acid stones.
      This study was performed to evaluate the efficacy of potassium alkali as
      potassium-magnesium citrate in reducing renal stone risk and bone turnover.
      MATERIALS AND METHODS: This study was performed as a double-blind, placebo
      controlled trial. We studied 20 normocalciuric subjects randomized to either
      placebo or potassium-magnesium citrate (42 mEq potassium, 21 mEq magnesium, 63
      mEq citrate per day) before and during 5 weeks of strict bed rest. The study was
      performed in the General Clinical Research Center and under a controlled dietary
      regimen composed of 100 mEq of sodium, 800 mg of calcium, 0.8 gm/kg animal
      protein and 2,200 kcal per day. Two 24-hour urine collections were obtained under
      oil each week for assessment of stone risk parameters and relative saturation of
      calcium oxalate, brushite and undissociated uric acid. Blood was also collected
      for determination of serum immunoreactive parathyroid hormone and vitamin D
      metabolites. RESULTS: Bed rest promoted a rapid increase in urinary calcium
      excretion of approximately 50 mg per day in both groups. Despite this increase
      subjects treated with potassium-magnesium citrate demonstrated significant
      decreases in the relative saturation of calcium oxalate and in the concentration
      of undissociated uric acid compared to placebo. Immunoreactive parathyroid
      hormone, serum 1,25-dihydroxyvitamin D and intestinal calcium absorption all
      decreased in both groups with no difference in response between the 2 treatment
      arms. CONCLUSIONS: Provision of alkali as potassium-magnesium citrate is an
      effective countermeasure for the increased risk of renal stone disease associated
      with immobilization. Despite an increase in urine calcium concentration, the
      relative saturation of calcium oxalate decreased due to citrate chelation of
      calcium and the concentration of undissociated uric acid decreased due to the
      significant increase in urine pH.

PMID- 17509314
TI  - Is there a role for tamsulosin in shock wave lithotripsy for renal and ureteral
      calculi?
AB  - PURPOSE: We evaluated the effect of the alpha-blocker tamsulosin on stone
      clearance, analgesic requirements and steinstrasse in shock wave lithotripsy for
      solitary renal and ureteral calculus. MATERIALS AND METHODS: A prospective,
      double-blind, randomized placebo controlled study was performed during 1 year
      involving 60 patients with a solitary renal or ureteral calculus undergoing shock
      wave lithotripsy. The control group (30) received 0.4 mg tamsulosin and the study
      group (30) received placebo daily until stone clearance or for a maximum of 30
      days. An oral preparation of dextropropoxyphene hydrochloride and acetaminophen
      was the analgesic used on an on-demand basis. The parameters assessed were stone
      size, position, clearance time, effect on steinstrasse and analgesic requirement.
      RESULTS: The overall clearance rate was 96.6% (28 of 29) in the study group and
      79.3% (23 of 29) in the control group (p = 0.04). With larger stones 11 to 24 mm
      the difference in the clearance rate was significant (p = 0.03) but not so with
      the smaller stones 6 to 10 mm (p = 0.35). The average dose of analgesic used was
      lower with tamsulosin than with controls, without statistical significance.
      Steinstrasse resolved spontaneously in the tamsulosin group whereas 25% (2 of 8)
      required intervention in the placebo group. There was no difference between the 2
      groups with regard to age, stone size or location. CONCLUSIONS: The alpha-blocker
      tamsulosin seemed to facilitate stone clearance, particularly with larger stones
      during shock wave lithotripsy for renal and ureteral calculus. It also appeared
      to improve the outcome of steinstrasse. Tamsulosin may have a potential role in
      routine shock wave lithotripsy.

PMID- 17509316
TI  - Genitourinary trauma at a combat support hospital during Operation Iraqi Freedom:
      the impact of body armor.
AB  - PURPOSE: This report details the occurrences of genitourinary trauma experienced
      during Operation Iraqi Freedom at a United States Army Combat Support Hospital,
      and determines if wearing body armor decreases the frequency of genitourinary and
      specifically kidney trauma. MATERIALS AND METHODS: The Joint Theater Trauma
      Registry was used to conduct a retrospective study of 2,712 trauma admissions to
      a United States Army Combat Support Hospital in Baghdad, Iraq from April 1, 2005
      to February 28, 2006. There were 1,216 casualties who were wearing body armor and
      1,496 casualties not wearing body armor. RESULTS: Of the 2,712 trauma admissions
      76 (2.8%) had 1 or more genitourinary injuries for a total of 98 genitourinary
      injuries. Of the 29 kidney injuries 2 (6.9%) were explored without any treatment,
      7 (24.1%) were observed, 1 (3.4%) was repaired and 19 (65.5%) casualties required
      nephrectomy. Casualties wearing body armor had a 2.1% rate of genitourinary
      injury versus 3.4% not wearing body armor (p = 0.037). Casualties wearing body
      armor had a 0.5% rate of kidney injury compared to 1.4% not wearing body armor (p
      = 0.017). CONCLUSIONS: The percentage of casualties with genitourinary injuries
      and the distribution of these injuries appear similar to previous conflicts. The
      percentage of casualties undergoing nephrectomy appears to be greater than that
      observed in other recent conflicts. There was a significant reduction in overall
      genitourinary injuries and specifically kidney injuries in those casualties
      wearing body armor.

PMID- 17509315
TI  - Prospective long-term followup of patients with asymptomatic lower pole caliceal
      stones.
AB  - PURPOSE: The intervention time of asymptomatic lower pole calculi remains
      controversial. In this prospective study we evaluated the natural history and
      progression rate of asymptomatic lower pole stones. MATERIALS AND METHODS:
      Patients were followed every 6 months. Computerized tomography in even years,
      ultrasound scan in odd years after initial visit and abdominal plain films
      between these visits were evaluated. The largest diameter was measured for each
      calculus and the cumulative diameter was calculated for cases of multiple stones.
      Disease progression was defined as pain experienced during followup, stone growth
      or the need for intervention. RESULTS: A total of 24 patients, 14 male and 10
      female, were followed for a mean of 52.3 months (range 24 to 72). Of the 24
      patients 3 had bilateral lower pole stones. Mean cumulative stone diameter at
      presentation was 8.8 mm (range 2.0 to 26.0). Progression in stone size was
      demonstrated in 9 of 27 renal units (33.3%) with 2 (11.1%) requiring
      intervention. There was no need for intervention during the first 2 years of
      followup. Three stones passed spontaneously without any symptoms. Pain developed
      in 3 patients during followup, and 2 of them passed a stone and responded to the
      analgesics without further treatment. None of the patients had a pyelonephritic
      attack during followup. CONCLUSIONS: Our results showed that observation could be
      considered for patients with asymptomatic lower pole stones. However, patients
      should be counseled about the 33% disease progression and 11% intervention rates.

PMID- 17509319
TI  - Salvage prostatectomy with bladder neck closure, continent catheterizable stoma
      and bladder augmentation: feasibility and patient reported continence outcomes at
      32 months.
AB  - PURPOSE: Salvage prostatectomy after radiation therapy is associated with a high
      rate of urinary incontinence. To avoid this outcome in candidates with
      preexisting voiding symptoms, such as frequency, urgency and urge incontinence,
      we performed concurrent bladder augmentation with bladder neck closure and a
      catheterizable stoma. Urinary incontinence and patient satisfaction were
      evaluated. MATERIALS AND METHODS: Between October 2000 and February 2003, 11
      patients underwent salvage prostatectomy with bladder neck closure and ileal
      augmentation using catheterizable appendicovesicostomy or Monti ileovesicostomy.
      Self-reported outcome measures included patient questionnaires and the validated
      Incontinence Symptom Index. RESULTS: The indication for surgery was recurrent
      adenocarcinoma of the prostate in 10 patients and invasive squamous cell
      carcinoma of the urethra in 1. All patients underwent prior radiation. Mean +/-
      SD followup after prostatectomy and reconstruction was 32 +/- 7.5 months. The
      physician noted that 8 of 11 patients (73%) were dry. Nine of 11 patients (82%)
      returned the questionnaire. Only 2 of 9 patients (22%) reported using absorbent
      protection. By self-report and the Incontinence Symptom Index 4 of 9 patients
      (44%) reported no leakage and only 3 (33%) had leakage more frequently than once
      weekly. Three of 11 patients (27%) required stomal revision at an average of 24
      +/- 17 months, of whom 2 still reported difficult catheterization. Seven of 9
      patients (77%) reported that they would repeat the procedure. CONCLUSIONS:
      Continent catheterizable bladder augmentation is a technically feasible option
      for men requiring salvage prostatectomy. The postoperative continence rate is
      excellent and it appears superior to that in the literature for salvage
      prostatectomy with vesicourethral anastomosis.

PMID- 17509321
TI  - Reconstruction of the female urethra: versatility, complexity and aptness.
AB  - PURPOSE: Female urethral anomalies, whether congenital or acquired, are rare.
      Urethral defects are usually if not always associated with variable degrees of
      incontinence. In this case series we demonstrate the approach in management and
      surgical outcome of congenital and traumatic urethral anomalies. MATERIALS AND
      METHODS: The study was conducted on 13 patients with an age range of 2 to 38
      years (median 20). Of these patients 4 had female epispadias, 1 had hypospadias,
      3 had traumatic urethral loss and 2 had iatrogenic trauma involving the urethra.
      There were 2 patients with urogenital sinus syndrome and 1 patient had urethral
      prolapse. RESULTS: After the first stage of repair 4 patients were dry and
      socially satisfied, and no further intervention was needed. However, in 9
      patients a second intervention was necessary to achieve continence. Notably 3
      patients empty the bladder through clean intermittent catheterization.
      CONCLUSIONS: Female urethral defects are usually complex. Congenital causes are
      associated with severe incontinence. Repair of such defects is challenging, yet 1
      stage reconstruction is feasible and potentially successful.

PMID- 17509322
TI  - Augmented anastomotic urethroplasty.
AB  - PURPOSE: During substitution urethroplasty, if the stricture contains a 1 to 2 cm
      region that is particularly narrow and/or fibrotic, that portion may be excised
      with subsequent anastomosis of the dorsal or ventral aspect of the urethra to
      shorten, widen and optimize the urethral wall onto which an onlay graft is to be
      placed. This procedure is termed augmented anastomotic urethroplasty. To
      determine the effectiveness of this approach we reviewed our experience with
      augmented anastomotic urethroplasty in an 8-year period. MATERIALS AND METHODS:
      We reviewed the records of patients who underwent augmented anastomotic
      urethroplasty between October 1997 and April 2005. Perioperative characteristics
      were compared between successes and failures using the Wilcoxon/Kruskal-Wallis
      and Fisher exact tests. RESULTS: Of 69 patients who underwent augmented
      anastomotic urethroplasty for recurrent urethral strictures 5 had undergone
      previous urethroplasty using a genital skin flap or graft. At a median followup
      of 34 months (range 13 to 103) 62 patients had no evidence of stricture
      recurrence and required no further intervention for an overall success rate of
      90%. Stricture recurrence, defined as the inability to easily pass a standard
      flexible cystoscope through the area of repair, occurred in 7 patients (10%).
      Patients with stricture recurrence were significantly older (mean age 52 vs 39
      years, p = 0.02) and more likely to experience postoperative urinary tract
      infection (28% vs 3.2%, p = 0.05) than patients without repeat stricture.
      CONCLUSIONS: Augmented anastomotic urethroplasty is an effective technique that
      allows the use of a shorter onlay graft. It may optimize overall results due to
      improvement in the urethral wall and the associated corpus spongiosum.

PMID- 17509324
TI  - Long-term multi-institutional evaluation of Charleston pouch I continent
      cutaneous urinary diversion.
AB  - PURPOSE: Charleston pouch I continent cutaneous urinary diversion has been used
      since 1989. We evaluated the long-term results of this procedure in 201
      consecutive patients. MATERIALS AND METHODS: The records of patients treated with
      the Charleston pouch I between 1989 and 2005 at 3 university hospitals were
      reviewed. Available data on age, sex, indications for diversion, comorbidity,
      followup duration, continence status, short-term and long-term complications,
      quality of life issues, and laboratory, radiological and urodynamic data were
      recorded. Patients were followed at 6-month intervals. RESULTS: Followup was 14
      to 136 months. Seven adults died in the 90-day postoperative period, and 21
      (10.8%) and 51 (26%) patients had early and late complications, respectively. The
      interval between clean intermittent catheterizations was 2 to 8 hours. Mean
      capacity was 470 ml (range 250 to 1,300). At 12 months diurnal continence was
      achieved in 98% of the patients. A total of 98 patients (50.5%) needed night
      catheterization to stay dry. Of 342 ureters 17 (5%) became obstructed, requiring
      open or endoscopic management. Urolithiasis developed in 16 patients (8%).
      Vesicoureteral reflux was noted in 15 renal units (4.4%). Stomal complications
      developed in 8.2% of cases. Modest vitamin B12 supplementation was empirically
      used to avoid long-term deficiency. No detrimental effects on vitamin B12
      concentrations were noted for up to 10 years. CONCLUSIONS: Long-term multi
      institutional followup of the classic Charleston pouch I reveals that it provides
      adequate continence with an acceptable complication rate and satisfactory patient
      acceptance.

PMID- 17509325
TI  - Orgasm associated incontinence (climacturia) following radical pelvic surgery:
      rates of occurrence and predictors.
AB  - PURPOSE: Orgasm associated incontinence, that is the inadvertent leakage of urine
      at orgasm, has received little attention in the literature. We evaluated the rate
      of occurrence of orgasm associated incontinence following radical pelvic surgery
      as well as its associated factors and predictors. MATERIALS AND METHODS: From
      January 2005 to March 2006, 696 patients were evaluated for post-radical pelvic
      surgery sexual dysfunction. A database was created, and descriptive statistics,
      chi-square analysis and logistic regression analysis were used to evaluate
      associated factors and predictors. RESULTS: Of 475 patients 96 (20%) reported
      orgasm associated incontinence following radical pelvic surgery. The incidence
      was significantly less in the cystoprostatectomy group than in the open and
      laparoscopic radical prostatectomy groups (p <0.05). Orgasm associated
      incontinence was more commonly found within 12 months following surgery vs
      greater than 12 months (RR 0.81, 95% CI 0.72-0.92, p <0.01) and in patients with
      orgasm associated pain (RR 1.09, 95% CI 1.01-1.16, p <0.01) and penile length
      loss (RR 1.32, 95% CI 1.09-1.59, p <0.01). On multivariate analysis all factors
      associated on univariate analyses remained predictive. Orgasm associated
      incontinence was not associated with patient age, the degree of nerve sparing,
      surgical margin status, seminal vesicle or lymph node involvement, preoperative
      erectile function, nocturnal erections, libido level or daytime continence.
      CONCLUSIONS: Orgasm associated incontinence occurs in a fifth of men (96 of 475)
      following radical pelvic surgery. The incidence of orgasm associated incontinence
      is greater with radical prostatectomy than with radical cystectomy and it is
      unrelated to the type of prostatectomy performed (open vs laparoscopic). Orgasm
      associated incontinence is more likely to be reported within year 1 following
      surgery and in men who complain of orgasmic pain and/or penile shortening.

PMID- 17509326
TI  - Short-term effects of desmopressin on water and electrolyte excretion in adults
      with nocturnal polyuria.
AB  - PURPOSE: Increased calcium excretion due to desmopressin has been reported in
      children with nocturnal enuresis. Desmopressin is often used to treat adult
      patients with nocturnal polyuria. However, data on the effect of desmopressin on
      water/electrolyte excretion in adults are scarce. We present the short-term
      effects of desmopressin on water and electrolyte excretion in adult patients with
      nocturnal polyuria. MATERIALS AND METHODS: A total of 16 male patients with
      nocturnal polyuria, mean age 76.3 years, received 0.1 or 0.2 mg desmopressin
      before sleep. Frequency volume chart was recorded, and daytime and nighttime
      urine samples were collected separately before and after desmopressin
      administration. Urinary excretions of sodium, potassium and calcium were
      determined, and compared before and after treatment with desmopressin. RESULTS:
      Desmopressin significantly increased urine osmolality, decreased nocturnal total
      urine volume, reduced the ratio of nocturnal urine volume-to-whole day urine
      volume and decreased nocturnal voiding frequency. Nocturnal urinary excretion of
      calcium (mean 0.137 vs 0.169 mg/kg body weight per hour, p = 0.004) and whole day
      excretion of calcium (mean 165.9 vs 200.0 mg per day, p = 0.012) were increased
      after desmopressin treatment. Nocturnal urinary potassium excretion (mean 0.030
      vs 0.025 mEq/kg body weight per hour, p = 0.030) and whole day potassium
      excretion (mean 40.7 vs 36.1 mEq per day, p = 0.017) were decreased by
      desmopressin treatment. However, desmopressin treatment did not significantly
      change urinary secretion of sodium and chloride at nighttime or for the whole
      day. CONCLUSIONS: Desmopressin reduces nocturnal urine volume and nocturnal
      voiding frequency in male patients with nocturnal polyuria. However, increased
      calcium and decreased potassium excretion following desmopressin treatment
      deserve attention particularly when it is used on a long-term basis.

PMID- 17509328
TI  - Efficacy of botulinum toxin-A for treating idiopathic detrusor overactivity:
      results from a single center, randomized, double-blind, placebo controlled trial.
AB  - PURPOSE: We evaluated the use of botulinum toxin-A in treating patients with
      idiopathic detrusor overactivity refractory to anticholinergics. MATERIALS AND
      METHODS: This double-blind, placebo controlled trial randomized participants to
      intradetrusor injections of 200 U botulinum toxin-A (16 patients) or placebo (18
      patients). The primary outcome measure was change in maximum cystometric
      capacity. Secondary outcome measures included changes in overactive bladder
      symptoms, post-void residual, maximum detrusor pressure during filling cystometry
      and reflex detrusor volume. Quality of life was assessed using the Incontinence
      Impact Questionnaire short form 7 and Urogenital Distress Inventory short form 6.
      Followup occurred at 4 and 12 weeks after injection, at which point the study was
      unblinded. Further followup in the botulinum toxin-A group occurred at 24 weeks.
      RESULTS: Significant increases in maximum cystometric capacity were observed at 4
      weeks (difference 144.69 ml, 95% CI 100.95 to 215.75, p <0.0001) and 12 weeks
      (difference 95.71 ml, 95% CI 47.47 to 172.45, p = 0.001) in patients treated with
      botulinum toxin-A compared to placebo. Botulinum toxin-A reduced frequency (p
      <0.001, p = 0.003) and urgency urinary incontinence (p = 0.03, p = 0.008)
      episodes at 4 and 12 weeks, respectively. Urgency was reduced at 4 weeks (p =
      0.005) in the botulinum toxin-A group. In patients receiving botulinum toxin-A,
      post-void residual increased at 4 weeks (p = 0.024) but became insignificant by
      12 weeks (p = 0.406). Of these patients 6 required intermittent self
      catheterization. Significant improvements in quality of life were observed
      following botulinum toxin-A. The extension study suggests that the beneficial
      effects of botulinum toxin-A are maintained for at least 24 weeks. CONCLUSIONS:
      Botulinum toxin-A at 200 U is safe and effective for idiopathic detrusor
      overactivity and the beneficial effects persist for at least 24 weeks.

PMID- 17509329
TI  - Bilateral caudal epidural neuromodulation for refractory urinary retention: a
      salvage procedure.
AB  - PURPOSE: Sacral neuromodulation with InterStim is approved for idiopathic urinary
      retention with a success rate of approximately 69%. To our knowledge currently no
      alternatives exist for patients in whom S3 neuromodulation fails. We report a new
      technique and our experience with bilateral caudal epidural neuromodulation in
      patients in urinary retention in whom unilateral or bilateral S3 InterStim
      failed. MATERIALS AND METHODS: Eight patients with multifactorial urinary
      retention in whom S3 InterStim previously failed underwent retrograde placement
      of bilateral tined leads into the caudal epidural space for sacral nerve
      stimulation. Patients with a 50% or greater clinical response underwent stage 2
      Synergy-Versitrel implantable pulse generator placement. Patients were evaluated
      with voiding diaries, the Urinary Distress Inventory Questionnaire short form,
      quality of life assessment, need for catheterization and post-void residual urine
      preoperatively, and 6 months after implantation. RESULTS: Five of the 8 patients
      experienced return of micturition and underwent placement of a permanent
      implantable pulse generator. At 6-month followup 4 of the 5 patients voided to
      completion. One patient improved more than 50% and now catheterizes once daily
      with a post-void residual urine of 200 cc. There was a significant decrease in
      obstructive symptoms on the Urinary Distress Inventory Questionnaire short form
      and improved overall quality of life. CONCLUSIONS: To our knowledge this is the
      first report of the use of bilateral caudal epidural neuromodulation for
      refractory urinary retention. This therapy can be successful in patients in whom
      prior InterStim therapy failed.

PMID- 17509331
TI  - Selective, concurrent bilateral nephrectomies at renal transplantation for
      autosomal dominant polycystic kidney disease.
AB  - PURPOSE: An algorithm was developed for performing bilateral nephrectomies for
      specific indications before or at renal transplantation in patients with
      autosomal dominant polycystic kidney disease. Outcomes for the living donor arm
      of the algorithm are reported. MATERIALS AND METHODS: Patients with autosomal
      dominant polycystic kidney disease and end stage renal disease were evaluated for
      transplantation. Patients with recurrent pyelonephritis, hemorrhage, pain, early
      satiety or kidneys that extended into the true pelvis underwent bilateral
      nephrectomies. Bilateral nephrectomies with concurrent renal transplantation were
      performed if a living renal donor was identified. If no living donor was
      identified, pre-transplantation bilateral nephrectomies were done and the
      patients were listed for cadaveric donor renal transplantation. The living renal
      donor arm of the algorithm was evaluated by comparing certain parameters for 15
      and 17 patients with autosomal dominant polycystic kidney disease who underwent
      pre-transplantation and concurrent bilateral nephrectomies, respectively,
      including patient and graft survival, delayed graft function, graft function,
      length of stay for each surgery, transfusions and complications. RESULTS: No
      deaths, graft failures or delayed graft function occurred. In the delayed renal
      transplant group median time from nephrectomy to living donor transplantation was
      124 days. Serum creatinine at discharge home and 1 year after transplantation for
      the pre-transplantation nephrectomy cohort was 2.0 and 1.3 mg/dl, respectively.
      Seven of the 17 patients with concurrent nephrectomy underwent transplantation
      before starting renal replacement therapy. A longer mean total hospital stay in
      the pre-transplantation nephrectomy cohort was the only statistically
      significance outcome variable. CONCLUSIONS: Selective bilateral nephrectomies at
      living donor renal transplantation results in decreased total length of stay
      without compromising patient or graft outcomes and it allows preemptive renal
      transplantation. Concurrent nephrectomy is safe and it further validates the
      algorithm for selective, concurrent bilateral nephrectomies for patients with
      autosomal dominant polycystic kidney disease who undergo living donor renal
      transplantation.

PMID- 17509333
TI  - Operative mortality after renal transplantation--does surgeon type matter?
AB  - PURPOSE: Currently there are 64 accredited renal transplantation fellowships in
      Canada and the United States. Only 27% are limited in scope to kidney
      transplants. In the remaining fellowships the trainee learns to transplant
      multiple abdominal organs. Given this evolution to the multiorgan transplant
      surgeon, we evaluated the effect of the current training paradigm on practice
      patterns and outcomes for kidney transplants. MATERIALS AND METHODS: Using data
      from the Nationwide Inpatient Sample, discharge records for kidney transplants
      (6,674) were abstracted (1993 to 2003). Through the Nationwide Inpatient Sample
      unique surgeon identifier we determined the proportion of kidney transplants
      performed by multiorgan and kidney only transplant surgeons. We fit multilevel
      regression models to examine the relationship between surgeon type and transplant
      outcome. RESULTS: We identified 99 multiorgan and 196 kidney only transplant
      surgeons who performed 3,255 and 3,419 kidney transplants, respectively. Kidney
      only transplant surgeons were more likely than multiorgan surgeons to practice in
      nonteaching, private, for-profit hospitals (p <0.05). Unadjusted operative
      mortality was higher in patients treated by kidney only vs multiorgan transplant
      surgeons (1.7% vs 0.9%, p = 0.002). After adjusting for patient and hospital
      factors, those who underwent renal transplantation performed by multiorgan
      transplant surgeons had 55% lower odds of inpatient death (OR 0.45, 95% CI 0.26
      0.76) vs kidney only transplant surgeons. CONCLUSIONS: Despite the current
      training paradigm, kidney only transplant surgeons have a prominent role in renal
      transplantation. However, given the current donor organ shortage and the
      implications for quality, the observed mortality difference suggests that
      additional investigation is needed to determine whether this role should be
      decreased.

PMID- 17509336
TI  - Impact of stents on urological complications and health care expenditure in renal
      transplant recipients: results of a prospective, randomized clinical trial.
AB  - PURPOSE: We performed a randomized, prospective trial to compare the incidence of
      early urological complications and health care expenditures in renal transplant
      recipients with or without ureteral stenting. MATERIALS AND METHODS: Patients
      receiving a renal transplant at a single center were randomized preoperatively to
      undergo Double-J stent or no-stent ureterovesical anastomosis from November 1998
      to October 2001. Early urological mechanical complications were recorded,
      including urinary leakage or obstruction, or urinary tract infections within 3
      months of transplantation. Direct health care costs associated with stenting,
      urological complications and urinary tract infection management were also
      collected. RESULTS: A total of 201 patients were randomized to a stent (112) and
      a no-stent (89) group. In the no-stent group 11 patients received a stent due to
      intraoperative findings and were excluded from study. At 3 months there were
      significantly more cases of urinary leakage (8.9% vs 0.9%, p <0.008) and ureteral
      obstruction (7.7 % vs 0%, p <0.004) in the no-stent than in the stent group. Mean
      time of stent removal was 74.3 days. A significant increase in urinary tract
      infections was observed when stent was left greater than 30 days after
      transplantation compared to the rate in the no-stent group (p <0.02). An
      additional cost of 151 UK pounds per patient was incurred in the no-stent group
      vs the stent group. CONCLUSIONS: Using a ureteral stent at renal transplantation
      significantly decreases the early urinary complications of urine leakage and
      obstruction. However, there is a significant increase in urinary tract
      infections, primarily beyond 30 days after transplantation. Stent removal within
      4 weeks of insertion appears advisable.

PMID- 17509338
TI  - Is sildenafil citrate associated with an amelioration of the symptomatology of
      androgen decline in the aging male?
AB  - PURPOSE: We examined whether treatment of erectile dysfunction with sildenafil
      citrate is associated with amelioration of the symptomatology of androgen decline
      in the aging male, and whether this alters the endocrine pattern. MATERIALS AND
      METHODS: A double-blind, randomized, placebo controlled, crossover study with
      sildenafil citrate was conducted in 60 men (age range 47 to 75 years old) who
      presented with erectile dysfunction and screened positively for androgen decline
      in the aging male by the questionnaire of the same name. The patients were
      randomized to receive sildenafil citrate or placebo in a 1:1 ratio and were
      crossed over after 3 months of treatment for an additional 3 months. The
      evaluation included International Index Erectile Function and Aging Male Symptoms
      questionnaires, hormonal profiles, total testosterone, and bioavailable
      testosterone. RESULTS: A total of 40 patients completed the study. Compared to
      placebo, sildenafil citrate improved erectile function (52.7 +/- 2 vs 39 +/- 1.9,
      p <0.001) and Aging Male Symptoms score (33.5 +/- 1.3 vs 28.6 +/- 1.3, p <0.001)
      in the total group. Breakdown into hypogonadal and normal men showed that the
      International Index of Erectile Function score improved more in normal (Delta
      18.5 +/- 3.6) than in hypogonadal men (Delta 6.7 +/- 2.7). There were no
      differences in improvement on the Aging Male Symptoms questionnaire between
      hypogonadal and normal men. No treatment changes were observed in total
      testosterone and bioavailable testosterone. CONCLUSIONS: In the total group of
      patients sildenafil citrate was associated with expected improvement in erectile
      function and in the Aging Male Symptoms questionnaire without any alteration in
      hormonal pattern. The available questionnaires for androgen decline in the aging
      male are not specific for the diagnosis of biochemical androgen decline in the
      aging male, although the suboptimal response to sildenafil citrate suggests the
      presence of hypogonadism.

PMID- 17509339
TI  - The kinetics of the return of motile sperm to the ejaculate after vasectomy
      reversal.
AB  - PURPOSE: In prior analyses we observed that the achievable patency rate after
      vasectomy reversal is a key factor in whether reversal surgery is more cost
      effective than in vitro fertilization-intracytoplasmic sperm injection for
      fertility after vasectomy. Because pregnancies will occur sooner with an earlier
      time to patency, this clinical parameter becomes important with advanced maternal
      age. We hypothesize that there are predictors of time to patency after reversal
      that are valuable for patient counseling and intraoperative decision making in
      cases of advanced maternal age. MATERIALS AND METHODS: We retrospectively
      reviewed a cohort of consecutive men who underwent vasectomy reversal. Data
      obtained included patient demographics, semen analyses, intraoperative findings,
      patency rates and time to achieve patency. RESULTS: A total of 150 patients met
      the inclusion criteria. Mean patient age was 42.9 years (range 27 to 61) and mean
      followup was 12.5 months (range 1 to 90). The presence of motile sperm in vasa
      predicted faster patency rates postoperatively. Of patients with motile sperm 95%
      achieved patency by 6 months whereas 76% of patients without motile sperm
      achieved patency within 6 months (p = 0.04). An obstructive interval of 8 years
      or less and undergoing vasovasostomy instead of epididymovasostomy predicted
      faster time to patency within the first 3 months after reversal. Patient age was
      not associated with time to patency after bilateral vasovasostomy. CONCLUSIONS:
      Motile sperm found intraoperatively at the testicular vas, undergoing
      vasovasostomy and an obstructive interval of 8 years or less predict shorter time
      to patency after vasectomy reversal. Patient age does not appear to affect
      patency kinetics after reversal. Patient counseling regarding fertility after
      vasectomy may benefit from this information especially in the setting of advanced
      maternal age.

PMID- 17509340
TI  - The virtual reality transurethral prostatic resection trainer: evaluation of
      discriminate validity.
AB  - PURPOSE: To understand how urologists acquire resection skills we analyzed
      factors correlating with favorable resection metrics in groups defined as
      experts, residents and novices. We then evaluated discriminate validity by
      determining factors correlating with proficiency among individuals in the expert,
      resident and novice groups. MATERIALS AND METHODS: A total of 136 subjects
      completed the protocol, including 72 urologists, 45 residents and 19 novices.
      After a pre-task questionnaire and training video subjects performed a
      standardized 5-minute resection task. Primary metrics were gm resected, blood
      loss, irrigant volume used, foot pedal use and differential time spent with
      orientation, cutting or coagulation. RESULTS: Among experts larger resection
      correlated with more time spent cutting (p <0.001). In contrast, increased
      coagulation time correlated with gm resected in the novice group (p = 0.001). The
      number of transurethral prostate resections that residents reported having done
      in the real operating room correlated with gm resected (p = 0.043), use of more
      irrigating fluid (p = 0.024) and less time spent coagulating (p = 0.027) on the
      simulator. In residents and experts exclusively primary resection efficiency
      metrics, fluid use and blood loss correlated with cuts at tissue and correlated
      inversely with coagulation and orientation time (p <0.05). CONCLUSIONS: Different
      factors determine transurethral prostate resection performance metrics among
      experts, residents and novices. These correlations reinforce discriminate
      validity and provide insight into specific factors that likely determine success
      at different training levels. Such data could be used to isolate and train skill
      subsets in the curriculum and they may elucidate the safest and most efficient
      approach to train resection skills.

PMID- 17509341
TI  - Improving professionalism: making the implicit more explicit.
AB  - PURPOSE: Professionalism is one of the most challenging of the Accreditation
      Council for Graduate Medical Education Competencies to define, teach and
      evaluate. At University of Washington we assessed whether defining
      professionalism, and training faculty and residents in the evaluation process
      would improve professional behavior. MATERIALS AND METHODS: In 2003 the
      Accreditation Council for Graduate Medical Education Global Resident Competency
      Rating Form was distributed to faculty after each rotation to evaluate residents.
      The project included all 16 residents and 18 clinical faculty during a total of
      15 rotations for 3 years at 4 Seattle area hospitals. After 21 months a training
      lecture on professionalism was presented to faculty and residents. Following this
      intervention all trained faculty completed a Graduate Medical Education Global
      Resident Competency Rating Form on every resident after each rotation. Three
      specific professionalism questions from the Graduate Medical Education Global
      Resident Competency Rating Form were chosen as representations of standard
      professional behaviors. These questions were used to assess the change in
      resident professional behavior. RESULTS: Pre-intervention and post-intervention
      scores were compared. Mean post-intervention scores were higher by 0.4 to 0.5
      points for each of the 3 questions (each p <0.01). There was less variation in
      scores after the intervention, suggesting that 1) residents were more consistent
      in their professional behavior and/or 2) the faculty observation of resident
      professional behaviors was more focused. CONCLUSIONS: These results suggest that
      training faculty and residents in professionalism may have a significant positive
      influence on improving resident professional behavior as well as the faculty
      ability to more objectively evaluate resident professional behaviors based on
      defined standards.

PMID- 17509343
TI  - Neonatal bilateral testicular torsion: a plea for emergency exploration.
AB  - PURPOSE: Bilateral testicular torsion is a rare condition. Most authors present
      single case reports. Therefore, the clinical and surgical aspects of bilateral
      torsion in a neonate have not been subjected to detailed analysis. We performed a
      retrospective analysis of our experience in the management of bilateral perinatal
      torsion as well as a collective review of the medical literature. MATERIALS AND
      METHODS: All cases of neonatal testicular torsion managed at our neonatal
      surgical center during the last 2 decades (1986 to 2005) were reviewed, and 3
      cases of bilateral torsion were identified. In addition, 45 neonatal cases of
      bilateral torsion were found through the literature search. In all cases data
      regarding clinical presentation, imaging studies, surgical management,
      intraoperative and pathological findings, and final outcome were analyzed.
      RESULTS: Synchronous torsion occurred in 32 of 48 newborns (67%), while
      asynchronous pathology was reported in 16 (33%), including the 3 presented in
      this report. All except 1 patient were full-term newborns with normal or above
      average birth weight. Difficult delivery was noted in 33% of the cases. Despite
      prompt surgical intervention in 46 infants, the salvage rate was low, with
      arterial flow confirmed postoperatively in only 3 gonads (3.1%). Four gonads in 3
      additional patients were reported to be of normal size on followup. CONCLUSIONS:
      Asynchronous torsion is not as rare an event as previously reported, and it may
      pose a diagnostic challenge. In the majority of these cases torsion of the left
      testis seems to occur later than torsion of the right testis. The role of imaging
      studies in newborns with bilateral torsion seems to be limited, especially in
      cases of asynchronous pathology. Urgent bilateral exploration is strongly advised
      in all newborns presenting with either unilateral or bilateral torsion. Such
      policy carries diagnostic, potential therapeutic and prognostic implications.

PMID- 17509344
TI  - Urolithiasis in pediatric patients: a single center study of incidence, clinical
      presentation and outcome.
AB  - PURPOSE: The incidence of kidney stones in adults has increased in the last 30
      years. This retrospective, single site review was done to test the hypotheses
      that the incidence of urolithiasis in pediatric patients increased from 1994 to
      2005, and that metabolic abnormalities were more common in patients with renal
      stones in the final 3 years of the study period. MATERIALS AND METHODS: Charts
      from 2 time periods were reviewed, 1994 to 1996 (period 1) and 2003 to 2005
      (period 2). Clinical and laboratory data, including demographics, presenting
      complaints, laboratory assessment, treatment and outcome, were tabulated in
      patients with confirmed urolithiasis. RESULTS: The number of patients with
      urolithiasis increased from 7 in period 1 to 61 in period 2. When expressed as
      cases per 100 new patients the incidence increased 4.6 times (p = 0.014).
      Focusing on period 2, 28% of patients were younger than 10 years. While blood
      tests were generally normal, 76% of patients had at least 1 abnormality in the 24
      hour urine collection. Hypocitraturia, which was the most common metabolic
      abnormality, was noted in 52% of patients. The small number of patients in period
      1 precluded determination as to whether metabolic abnormalities were more common
      in period 2. Surgery and/or lithotripsy was required in 12 children. Stone
      disease recurred in 39% of the patients. CONCLUSIONS: The incidence of
      urolithiasis in the pediatric population increased nearly 5-fold at our
      institution during the last decade. We recommend that the primary diagnostic test
      be a 24-hour urine collection. The most common metabolic abnormality was
      hypocitraturia, followed by hypercalciuria. Recurrence of stones is common
      (approximately 40% rate) and followup is advised.

PMID- 17509345
TI  - Early results of robot assisted laparoscopic lithotomy in adolescents.
AB  - PURPOSE: The treatment of large stone burdens in children is difficult and often
      requires multiple procedures using a combination of therapies. Recently,
      laparoscopy has been shown to be effective in the management of larger stone
      burdens. We report our experience with robot assisted laparoscopic lithotomy in
      adolescents, and describe our technique. MATERIALS AND METHODS: We
      retrospectively reviewed our experience with robot assisted laparoscopic
      pyelolithotomy in 5 patients operated on between 2002 and 2005. Mean patient age
      at surgery was 16.6 years, and mean followup was 15.4 months. RESULTS: Cystine
      was the etiology in 4 patients with staghorn stones. The remaining patient had
      calcium oxalate stones and concurrent ureteropelvic junction obstruction. After
      pyelotomy stones were removed by a robotic grasper or by a flexible cystoscope
      introduced through a robotic port. One of the patients had an indwelling ureteral
      stent placed preoperatively, while 4 had stents placed robotically
      intraoperatively. Mean operative time was 315.4 minutes (range 165.0 to 462.0),
      and mean estimated blood loss was 19.0 ml (0.0 to 50.0). Mean hospital stay was
      3.8 days (range 2.3 to 5.7), and mean narcotic usage was 2.1 mg/kg morphine (1.5
      to 3.5). One patient with a cystine staghorn calculus required conversion to an
      open procedure because of inability to remove the stone. Of the 4 cases completed
      robotically 3 were rendered stone-free and 1 had a residual 6 mm lower pole
      stone. CONCLUSIONS: The early results of robot assisted laparoscopic lithotomy
      reveal that the procedure is safe and efficacious. Further prospective studies
      comparing other minimally invasive procedures used for similar stone burdens are
      needed to determine the benefits of this procedure and its role in stone
      management.

PMID- 17509347
TI  - Laparoscopic transureteroureterostomy: a novel approach.
AB  - PURPOSE: We describe the feasibility and short-term results of laparoscopic
      transureteroureterostomy in children. MATERIALS AND METHODS: We performed
      transperitoneal laparoscopic transureteroureterostomy with a 4-trocar technique
      in 3 children with a mean age of 63 months (range 18 to 105). Diagnoses were
      unilateral ureteral obstruction after cross-trigonal reimplantation for
      vesicoureteral reflux (1 patient), unilateral refluxing megaureter (1) and
      ureteral injury after bladder diverticulectomy (1). Cystoscopy, retrograde
      pyelogram and stent placement in the recipient ureter were performed at the
      beginning of each case. The anastomoses were carried out with running 6-zero
      reabsorbable sutures at the level of the pelvic bream. An abdominal drain and
      Foley catheter were left indwelling for 1 to 3 days. RESULTS: All cases were
      performed successfully. Postoperative course was uneventful except for a
      transient urinary leak, and patients were discharged home on postoperative day 2
      to 4. At a mean followup of 6 months all patients were clinically well, with
      normal kidney function and blood pressure, and no significant hydronephrosis.
      CONCLUSIONS: Based on our initial experience, laparoscopic
      transureteroureterostomy is safe and effective, and is associated with little
      blood loss, minimal analgesia requirements, fast recovery and excellent cosmetic
      results. We believe that in selected cases in which transureteroureterostomy is
      the chosen technique a laparoscopic approach is advantageous.

PMID- 17509348
TI  - Initial experience with laparoscopic ipsilateral ureteroureterostomy in infants
      and children for duplication anomalies of the urinary tract.
AB  - PURPOSE: We report the feasibility of laparoscopic ipsilateral
      ureteroureterostomy for duplication anomalies of the urinary tract in infants and
      children, and the short-term results in 6 patients. MATERIALS AND METHODS:
      Laparoscopic ipsilateral ureteroureterostomy was performed transperitoneally with
      3 and 4 ports for unilateral and bilateral cases, respectively. Cystoscopy,
      retrograde pyelogram and stent placement in the recipient ureter were performed
      at the beginning of each case. The anastomosis was carried out with running or
      interrupted 6-zero sutures. An abdominal drain and Foley catheter were left
      indwelling in all cases. Demographic data, body measurements, type of procedure
      and indication, laterality, intraoperative and postoperative complications,
      analgesia requirement, length of hospitalization and outcome were recorded.
      RESULTS: Eight laparoscopic ipsilateral ureteroureterostomies were performed in 6
      patients (2 males). Mean patient age was 51 months. Diagnoses were bilateral
      lower pole vesicoureteral reflux (2 patients) and ectopic ureter (4). Mean
      operative time including cystoscopy was 257 minutes (range 140 to 430) and
      estimated mean blood loss was 2.7 ml. There were no intraoperative complications.
      Mean morphine requirement was 0.13 mg/kg. Two cases required acetaminophen only
      for pain management. All patients were discharged home with no narcotics at a
      median of 3 days postoperatively (range 1 to 7). There were 2 postoperative
      febrile urinary tract infections. Followup renal ultrasound demonstrated no
      significant hydronephrosis of the moieties involved. CONCLUSIONS: In this initial
      experience laparoscopic ipsilateral ureteroureterostomy was done safely and
      effectively even in small infants. Postoperative course was uneventful, with
      negligible blood loss and minimal analgesia requirement, and initial results were
      comparable to those of open surgery.

PMID- 17509349
TI  - Urodynamic evaluation in children with lipomeningocele: timing for neurosurgery,
      spinal cord tethering and followup.
AB  - PURPOSE: We assessed the usefulness of urodynamic testing for determining the
      optimal timing of surgery and for evaluating the development of bladder function
      in children with lipomeningocele. MATERIALS AND METHODS: We retrospectively
      evaluated 64 patients (40 females) 3 to 17 years old (mean 8.5) with
      lipomeningocele. Patients were divided into 3 groups based on age at surgery, ie
      younger than 12 months (34 patients), 12 to 36 months (17) and older than 36
      months (13). All patients underwent urodynamic testing preoperatively and during
      extended followup (mean 6.5 years, range 3 to 12). RESULTS: Bladder capacity and
      mean detrusor leak pressure improved in all groups but particularly in patients
      operated on within the first year of life. At the end of the study mean bladder
      capacity was 420 cc in patients younger than 12 months, 300 cc in those 12 to 36
      months old and 260 cc in those older than 36 months (p <0.01), and mean detrusor
      leak pressure was 37, 54 and 55 cm H(2)O, respectively (p <0.01). At the latest
      followup 65% of patients in the youngest group had improved urodynamic parameters
      vs 33% of those 12 to 36 months old and 28% of those older than 36 months.
      CONCLUSIONS: Urodynamic evaluation and the presence of neurological impairment
      have crucial roles in determining the optimal timing of surgery in patients with
      lipomeningocele, and in diagnosing the onset of tethered cord. Our data show that
      early surgical repair seems to reduce the risk of neurological deterioration of
      the lower urinary tract, and allows a more physiological development of urinary
      function.

PMID- 17509350
TI  - Efficacy of combined anticholinergic treatment and behavioral modification as a
      first line treatment for nonneurogenic and nonanatomical voiding dysfunction in
      children: a randomized controlled trial.
AB  - PURPOSE: This randomized blinded clinical study was designed to compare the
      efficacy of tolterodine treatment combined with behavioral modification,
      behavioral modification alone and behavioral modification plus placebo in
      children with nonneurogenic, nonanatomical voiding dysfunction. MATERIALS AND
      METHODS: A total of 72 children meeting inclusion criteria were randomly
      allocated to 1 of 3 groups. One group received tolterodine (1 mg twice daily)
      along with behavioral modification, 1 received behavioral modification only and 1
      received placebo with behavioral modification. A dysfunctional voiding scoring
      system questionnaire was completed for all patients at the beginning of the
      study, and at 1 and 3 months of treatment. RESULTS: A total of 71 patients were
      evaluated. The groups did not differ with respect to age, gender and symptom
      score before study enrollment (p >0.05). Repeated calculations of symptom scores
      at 1 month of the treatment revealed a significant decrease in symptoms in all 3
      groups, with a significant decrease in patients receiving tolterodine. In
      addition, at month 3 the symptom score of the tolterodine group was significantly
      lower compared to month 1, while scores remained steady in the behavioral
      modification and behavioral modification plus placebo groups. CONCLUSIONS:
      Tolterodine combined with behavioral modification for voiding dysfunction in
      children without neurological or anatomical abnormality can be recommended as a
      first line treatment before invasive evaluation.

PMID- 17509352
TI  - Prenatal diagnosis and neonatal management of congenital urethral diverticulum.
AB  - PURPOSE: We present a series of male neonates with prenatally detected anterior
      urethral diverticula and discuss postnatal management. MATERIALS AND METHODS: We
      retrospectively reviewed 3 cases of prenatally detected anterior urethral
      diverticula presenting between 1998 and 2005. RESULTS: An anterior urethral
      cystic mass was identified prenatally in all 3 patients. One mass spontaneously
      ruptured prenatally. The patient underwent diverticulectomy and urethroplasty at
      age 6 months. Two patients had obstructive uropathy with oligohydramnios and were
      delivered at 32 weeks of gestation. Both cases were managed by urethrostomy and
      subsequent diverticulectomy and urethroplasty at age 6 months. CONCLUSIONS:
      Infravesical obstruction from a urethral diverticulum can be accurately
      identified and differentiated from other causes prenatally. Marsupialization is
      an excellent option for temporary urinary diversion when the clinical situation
      precludes primary excision and repair.

PMID- 17509353
TI  - Large cell calcifying Sertoli cell tumor of testis.

PMID- 17509354
TI  - Cystolithiasis with concentric mural calcification following transurethral
      microwave thermotherapy.

PMID- 17509355
TI  - A novel bioluminescent tumor model of human renal cancer cell lines: an in vitro
      and in vivo characterization.
AB  - PURPOSE: Bioluminescent imaging permits sensitive in vivo detection and
      quantification of cells engineered to emit light. We developed a bioluminescent
      human renal cancer cell line for in vitro and in vivo studies. MATERIAL AND
      METHODS: The 2 human renal cell carcinoma cell lines SN12-C and SN12-L1 were
      stably transfected to constitutively express luciferase using a retroviral
      shuttle. The bioluminescent signal was correlated with tumor cell numbers in
      vitro. Parental and transfected cells were compared by growth kinetics and
      histology. Tumor burden after heterotopic injection in immune deficient mice was
      monitored up to 39 days. The kinetics of the bioluminescent signal was evaluated
      for 1 to 60 minutes following luciferin injection. RESULTS: Bioengineered renal
      cancer cell lines stably expressed luciferase. The growth kinetics of the cells
      in vitro and the histology of tumors resulting from implantation of these cells
      were unaffected by retroviral transfection with the luciferase gene. As few as
      1,000 cells could be reliably detected. The intensity of the bioluminescent
      signal correlated with the number of tumor cells in vitro. Photon emission in
      vivo and ex vivo correlated significantly with tumor weight at sacrifice. After
      intraperitoneal injection of luciferin there was a time dependent change in the
      intensity of the bioluminescent signal with maximum photon emission at 20 minutes
      (optimal 17 to 25). CONCLUSIONS: Luciferase transfected human renal cancer lines
      allow reliable, rapid, noninvasive and longitudinal monitoring of tumor growth in
      vivo. The ability to assess tumor development in vivo with time is economical and
      effective compared to end point data experiments.

PMID- 17509356
TI  - Antitumor effects of imidazoquinolines in urothelial cell carcinoma of the
      bladder.
AB  - PURPOSE: Imidazoquinolines (Toll-like receptor-7 agonists) are a class of
      synthetic immune modulating agents. Imiquimod, a member of this drug family, is
      currently used as first line topical therapy for genital condyloma. It recently
      showed clinical efficacy against several benign and malignant skin lesions,
      including actinic keratosis and basal cell carcinoma. Working primarily through
      the stimulation of a proinflammatory immune response, the mechanism of action of
      imiquimod may be similar to that through which bacillus Calmette-Guerin is
      thought to act. We hypothesized that imidazoquinolines have therapeutic potential
      against bladder cancer. We determined the in vitro and in vivo effects of
      imidazoquinolines against bladder cancer cells. MATERIALS AND METHODS: The human
      and murine J82, T24, TCC-SUP (American Tissue Culture Collection, Manassas,
      Virginia) and MBT-2 bladder cancer cell lines were cultured in normal culture
      medium or medium supplemented with imidazoquinoline. Effects on cell viability,
      apoptosis induction and cytokine production were evaluated. In addition, the
      effects of imidazoquinoline on in vivo bladder tumor growth were determined via
      intravesical instillation in an orthotopic bladder tumor model in the mouse.
      RESULTS: A dose dependent decrease in cell viability was observed in all tumor
      cell lines treated with imidazoquinoline. In addition, imidazoquinoline
      significantly induced apoptosis and cytokine production. In in vivo experiments
      most mice treated with imidazoquinoline showed only an intense inflammatory
      response with no evidence of tumor, while control mice showed tumor growth.
      CONCLUSIONS: Imidazoquinolines have potent direct activity against bladder cancer
      cells by decreasing cell viability and inducing apoptosis and cytokine
      production. In addition, in vivo data suggest antitumor effects in an orthotopic
      bladder cancer mouse model. Therefore, imidazoquinolines may have therapeutic
      potential as a synthetic intravesical agent against bladder cancer.

PMID- 17509357
TI  - Quantifying the impact of prostate volumes, number of biopsy cores and 5alpha
      reductase inhibitor therapy on the probability of prostate cancer detection using
      mathematical modeling.
AB  - PURPOSE: Previous studies demonstrated a negative correlation between prostate
      volume and biopsy yield. By decreasing prostate volume 5alpha-reductase
      inhibitors may enhance cancer detection, which may explain the greater detection
      of high grade tumors in the finasteride arm of the Prostate Cancer Prevention
      Trial. MATERIALS AND METHODS: A mathematical model was constructed to analyze the
      effects of prostate and tumor volumes, and biopsy core number on cancer
      detection. The effects of the volume reduction observed with finasteride in the
      Prostate Cancer Prevention Trial were also modeled, as was the potential
      reduction in tumor volume needed to explain the observed difference in prostate
      cancer detection. The model was also applied to the Reduction by Dutasteride of
      Prostate Cancer Events study. RESULTS: A higher number of biopsies are required
      to ensure a detection probability of 0.90 or greater in larger glands or with
      smaller tumors. In the Prostate Cancer Prevention Trial for a tumor volume of 1
      cc a 17% increase in the detection rate in the finasteride arm would be predicted
      if there was no change in tumor volume, likewise the rate would be 11% to 17% for
      the dutasteride arm of the Reduction by Dutasteride of Prostate Cancer Events
      study. The calculated reduction in tumor volume needed to explain the difference
      in cancer detection between the finasteride and placebo arms of the Prostate
      Cancer Prevention Trial would be 51% to 66%. CONCLUSIONS: This model provides
      guidance on the optimal number of biopsy cores that accord with an earlier model.
      These findings also suggest that, if there were no reduction in tumor volume,
      5alpha-reductase inhibitor therapy could lead to excess cancer detection,
      including high grade tumors.

PMID- 17509358
TI  - Cranberry products inhibit adherence of p-fimbriated Escherichia coli to primary
      cultured bladder and vaginal epithelial cells.
AB  - PURPOSE: Cranberry proanthocyanidins have been identified as possible inhibitors
      of Escherichia coli adherence to uroepithelial cells. However, little is known
      about the dose range of this effect. Furthermore, it has not been studied
      directly in the urogenital system. To address these issues we tested the effect
      of a cranberry powder and proanthocyanidin extract on adherence of a P-fimbriated
      uropathogenic E. coli isolate to 2 new urogenital model systems, namely primary
      cultured bladder epithelial cells and vaginal epithelial cells. MATERIALS AND
      METHODS: E. coli IA2 was pre-incubated with a commercially available cranberry
      powder (9 mg proanthocyanidin per gm) or with increasing concentrations of
      proanthocyanidin extract. Adherence of E. coli IA2 to primary cultured bladder
      epithelial cells or vaginal epithelial cells was measured before and after
      exposure to these products. RESULTS: Cranberry powder decreased mean adherence of
      E. coli IA2 to vaginal epithelial cells from 18.6 to 1.8 bacteria per cell (p
      <0.001). Mean adherence of E. coli to primary cultured bladder epithelial cells
      was decreased by exposure to 50 mug/ml proanthocyanidin extract from 6.9 to 1.6
      bacteria per cell (p <0.001). Inhibition of adherence of E. coli by
      proanthocyanidin extract occurred in linear, dose dependent fashion over a
      proanthocyanidin concentration range of 75 to 5 mug/ml. CONCLUSIONS: Cranberry
      products can inhibit E. coli adherence to biologically relevant model systems of
      primary cultured bladder and vaginal epithelial cells. This effect occurs in a
      dose dependent relationship. These findings provide further mechanistic evidence
      and biological plausibility for the role of cranberry products for preventing
      urinary tract infection.

PMID- 17509359
TI  - A polymorphism of matrix Gla protein gene is associated with kidney stones.
AB  - PURPOSE: Matrix Gla protein, a potent calcification inhibitor in arterial
      vessels, is also expressed in the kidney and is up-regulated following the
      administration of ethylene glycol, a precursor of oxalate. Considering the
      analogous characteristics between arterial calcification and kidney stones, we
      identified variants of the human matrix Gla protein gene and investigated whether
      there is an association between MGP genetic polymorphisms and kidney stones.
      MATERIALS AND METHODS: We studied single nucleotide polymorphisms in matrix Gla
      protein in 122 kidney stone cases and 125 controls. We resequenced the human
      genomic MGP gene, including the 1,000 bp promoter 5'-untranslated region, 4 exons
      and 3'-untranslated regions, and we performed systematic genetic analysis. A
      single nucleotide polymorphism was genotyped using a fluorescent 5'endonuclease
      assay and its association with kidney stones was analyzed. RESULTS: We observed
      19 polymorphisms. A single nucleotide polymorphism was associated with kidney
      stones (OR 0.51, 95% CI 0.30-0.87; p = 0.012). The G allele carrier had a 2-fold
      decreased kidney stone risk compared with A allele carriers in single nucleotide
      polymorphism 11 (OR 0.55, 95% CI 0.31-1.00, p = 0.047). We found no association
      between the polymorphism and kidney stone clinical characteristics. CONCLUSIONS:
      Our findings show that an MGP gene polymorphism is associated with kidney stones
      and influences genetic susceptibility to kidney stones. In the future functional
      assays of the polymorphism should permit better understanding of the role of
      matrix Gla protein genetic variants and kidney stones.

PMID- 17509360
TI  - Effects of inositol hexaphosphate (phytate) on calcium binding, calcium oxalate
      crystallization and in vitro stone growth.
AB  - PURPOSE: We measured and compared 3 activities of inositol hexaphosphate, also
      known as phytate, to explore their importance in relation to antilithogenic
      potential. MATERIALS AND METHODS: Calcium binding activity by inositol
      hexaphosphate was measured with a calcium electrode in artificial and whole
      urine. Calcium oxalate crystallization inhibition was measured by a 96-well plate
      turbidimetric method with artificial and whole urine. Effects on stone growth
      were measured in an in vitro system of 12 stones grown simultaneously (a stone
      farm) using artificial urine alone or supplemented with urinary macromolecules.
      RESULTS: Phytate decreased ionized calcium, increased the metastable limit,
      decreased the crystallization turbidity rate index and decreased the in vitro
      stone growth rate. The effective concentration for calcium binding reduction was
      about 2 orders of magnitude higher than that required for crystallization
      inhibition, which in turn was about 2 orders of magnitude higher than that
      required for stone growth inhibition. When human urine or artificial urine
      supplemented with urinary macromolecules was used, the effective concentration of
      phytate for inhibiting crystallization and stone growth was increased by about 1
      order of magnitude. CONCLUSIONS: Inhibition of crystallization by phytate does
      not depend on decreasing the effective ionized calcium concentration and
      inhibition of in vitro stone growth does not depend on inhibiting crystallization
      of the suspended crystals. To our knowledge this is the first demonstration of a
      quantitative distinction between the inhibition of crystallization and stone
      growth. Inhibition of in vitro stone growth in the presence of macromolecules
      occurred at concentrations consistent with urinary phytate excretion.

PMID- 17509361
TI  - Recovery of renal function after complete renal hilar versus artery alone
      clamping during open and laparoscopic surgery.
AB  - PURPOSE: It is generally accepted that simultaneous occlusion of the renal artery
      and vein during warm ischemia is more damaging than occlusion of the artery
      alone. Pneumoperitoneum during laparoscopy may impair venous backflow, negating
      the benefits of clamping the artery alone. We evaluated the effect of
      laparoscopic vs open surgery on the recovery of renal function after clamping of
      the renal artery and vein, and the artery alone in a solitary kidney porcine
      model. MATERIALS AND METHODS: Right laparoscopic nephrectomy was performed in 36
      pigs. After a 12-day recovery period the animals were randomized into 3 groups,
      including 1) 120-minute warm ischemia with renal artery and vein occlusion, 2)
      120-minute warm ischemia with artery alone occlusion and 3) control sham surgery.
      The groups were further subdivided into an open and a laparoscopic arm. Serum
      creatinine was assessed preoperatively, and on postoperative days 1, 3, 8 and 15.
      RESULTS: Artery alone clamping resulted in a significantly lower serum creatinine
      increase on postoperative days 1 and 3 in the open arm compared to the
      laparoscopic arm. Compared to open renal artery and vein clamping the increase in
      serum creatinine for open artery alone clamping was also significantly lower on
      postoperative days 1 and 3. No significant difference in postoperative serum
      creatinine was found between the laparoscopic artery alone, and the renal artery
      and vein arms at any time point. No significant serum creatinine changes were
      observed in the control sham surgery group compared to preoperative values at all
      followup time points. CONCLUSIONS: In this porcine model clamping of the artery
      alone during open surgery better protected the kidney from warm ischemia compared
      to renal artery and vein occlusion. This benefit was not observed during
      laparoscopic surgery. We speculated that the presence of pneumoperitoneum causes
      at least partial occlusion of the renal vein, thus, negating the benefit of renal
      artery clamping only.

PMID- 17509362
TI  - Biomechanical and biochemical assessment of properties of the anterior urethra
      after hypospadias repair in a rabbit model.
AB  - PURPOSE: We created a rabbit model to test hypospadias operations and investigate
      the biomechanical properties of the urethra at long-term followup using
      biomechanical and biochemical assessments. MATERIALS AND METHODS: A total of 38
      New Zealand White rabbits were randomized into 4 groups, including controls, sham
      operation and 2 operation groups (experimental creation of a hypospadias-like
      defect and acute repair, respectively). In operation group 1 the ventral urethral
      wall and dorsal plate were longitudinally incised, half of the ventral urethral
      wall was excised (hypospadias-like defect) and the incised urethra was
      tubularized (tubularized incised posterior plate urethroplasty group). In
      operation group 2 the urethra was mobilized from the corpora cavernosa, excised
      in its distal end (hypospadias-like defect) and advanced to the glanular tip
      (mobilization and advancement group). At 23 weeks postoperatively biochemical and
      biomechanical assessments were performed. RESULTS: Maximum urethral strength and
      stiffness, strain at maximum load and the collagen weight fraction were not
      significantly different among the groups. Urethral diameter was larger and the
      total amount of collagen was higher in the mobilization and advancement group
      only (p <0.05). The mechanical quality of urethral collagen was decreased in the
      2 operation groups (p <0.05). CONCLUSIONS: This animal model proved to be useful
      for testing hypospadias operations and urethral mechanical properties. At long
      term followup after experimental hypospadias repair biochemical and biomechanical
      assessments showed no differences among the groups in mechanical strength, strain
      and stiffness, and no indication of fibrosis. Consequently testing new
      hypospadias repair techniques and evaluating their biomechanical long-term
      results could be performed using hypospadiac animal models before clinical use.

PMID- 17509363
TI  - Effect of 5-hydroxytryptamine1 serotonin receptor agonists on noxiously
      stimulated micturition in cats with chronic spinal cord injury.
AB  - PURPOSE: The serotonin 5-hydroxytryptamine(1A/7) receptor agonist (R)-8-OH-DPAT
      (8-hydroxy-2-(di-n-propylamino)tetralin) (Sigma) and the 5
      hydroxytryptamine(1A/1B/1D) agonist GR-46611 (3-[3-(2-dimethylaminoethyl)-1H
      indol-5-yl]-N-(4-methoxybenzyl)acrylamide) (Tocris Cookson, Ellisville, Missouri)
      inhibit bladder activity during saline infusion into the bladder of cats with
      chronic spinal cord injury (saline infused, spinal cord injured cats), suggesting
      an effect on mechanosensitive bladder afferent C fibers or their targets. We
      investigated the effects of (R)-8-OH-DPAT and GR-46611 on bladder activity in
      chronic spinal cord injured cats during infusion of dilute acetic acid into the
      bladder to stimulate chemosensitive bladder afferent C fibers (acid infused,
      spinal cord injured cats). MATERIALS AND METHODS: Chloralose anesthetized, spinal
      cord injured cats were catheterized through the bladder dome for filling
      cystometry during 0.5% acetic acid infusion. Dose-response curves for (R)-8-OH
      DPAT (0.3 to 30 microg/kg intravenously) or GR-46611 (0.03 to 300 microg/kg
      intravenously) were followed by the 5-hydroxytryptamine(1A) antagonist WAY-100635
      (N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide) (Sigma)
      (300 microg/kg). Threshold volume, bladder capacity, residual volume, micturition
      volume and arterial pressure were measured and external urethral sphincter
      electromyogram was recorded. RESULTS: Acid infused, spinal cord injured cats
      responded to (R)-8-OH-DPAT but not to GR-46611 with dose dependent increases in
      threshold volume, capacity and residual volume (significant above 3 microg/kg).
      Effects of (R)-8-OH-DPAT were largely reversed by WAY-100635. Neither (R)-8-OH
      DPAT nor GR-46611 augmented external urethral sphincter electromyogram activity.
      CONCLUSIONS: Based on differences in the response to GR-46611 in saline vs acid
      infused, spinal cord injured animals it is tempting to speculate that 2 distinct
      populations of bladder afferent C fibers (1 chemosensitive and 1
      mechanosensitive) can initiate spinal bladder reflexes. Because 5
      hydroxytryptamine(1A) receptor agonists increased bladder capacity under saline
      or acid infused conditions, they are promising candidates for decreasing bladder
      hyperactivity and increasing bladder capacity in patients with chronic spinal
      cord injury.

PMID- 17509364
TI  - Estrogen receptor-alpha and beta are differentially distributed, expressed and
      activated in the fetal genital tubercle.
AB  - PURPOSE: We examined the ontogenic and sex specific expression of estrogen
      receptor-alpha and beta in mouse genital tubercles and assessed the effects of in
      utero estrogen exposure on these parameters. MATERIALS AND METHODS: Expression of
      the 2 genes was detected in mouse genital tubercles from fetuses collected on
      gestational days 12, 14, 16 and 18, and from newborns using immunohistochemistry
      and quantitative polymerase chain reaction. Pregnant dams were exposed to ethinyl
      estradiol or corn oil as the control. RESULTS: Estrogen receptor-alpha and beta
      proteins first appeared on gestational days 12 and 14, respectively. The 2
      proteins were expressed in the urethral plate and mesenchyma. Staining intensity
      was more prominent in the mesenchyma for estrogen receptor-alpha and in the
      urethral plate for estrogen receptor-beta. Female genital tubercles expressed
      more estrogen receptor-alpha than male genital tubercles (p <0.01), while
      estrogen receptor-alpha expression increased gradually in the 2 sexes until
      birth. Estrogen receptor-beta expression did not differ between males and
      females, and it showed no notable variation during fetal life. Ethinyl estradiol
      led to a 2.1 and 3.8-fold increase in estrogen receptor-alpha expression in
      females and in males with hypospadias (p = 0.002 and 0.04, respectively).
      Estrogen receptor-beta expression did not change in response to ethinyl
      estradiol. CONCLUSIONS: This study provides in vivo evidence that estrogen
      receptor-alpha expression in the genital tubercles of each sex increases until
      parturition but estrogen receptor-beta expression does not, implying genital
      tubercle sensitivity to estrogen increases during fetal life. Exogenous
      administration of estrogens results in a response of increased expression of
      estrogen receptor-alpha but not of estrogen receptor-beta. These differential
      findings for estrogen receptor-alpha and beta imply that the 2 receptors may have
      different roles in normal or anomalous genital tubercle development.

PMID- 17509366
TI  - Re: Dynamic contrast enhanced, pelvic phased array magnetic resonance imaging of
      localized prostate cancer for predicting tumor volume: correlation with radical
      prostatectomy findings. A. Villers, P. Puech, D. Mouton, X. Leroy, C. Ballereau
      and L. Lemaitre, J Urol 2006; 176: 2432-2437.

PMID- 17509368
TI  - Re: Prediagnosis prostate specific antigen velocity is associated with risk of
      prostate cancer progression following brachytherapy and external beam radiation
      therapy. S. E. Eggener, K. A. Roehl, O. Yossepowitch and W. J. Catalona, J Urol
      2006; 176: 1399-1403.

PMID- 17509370
TI  - Re: Transmesenteric laparoscopic pyeloplasty. F. R. Romero, A. A. Wagner, C.
      Trapp, S. Permpongkosol, M. Muntener, R. E. Link and L. R. Kavoussi, J Urol 2006;
      176: 2526-2529.

PMID- 17509371
TI  - Re: Renal and bladder functional status at diagnosis as predictive factors for
      the outcome of primary vesicoureteral reflux in children. C. K. Yeung, B.
      Sreedhar, J. D. Sihoe and F. K. Sit, J Urol 2006; 176: 1152-1157.

PMID- 17509372
TI  - Re: Management of lower urinary tract symptoms secondary to benign prostatic
      hyperplasia with open prostatectomy: results of a contemporary series. B.
      Helfand, S. Mouli, R. Dedhia and K. T. McVary, J Urol 2006; 176: 2557-2561.

PMID- 17509374
TI  - Re: Editorial comment. D. A. Canning, J Urol 2006; 176: 2242.

PMID- 17509377
TI  - Re: Abstracts presented at the American Urological Association annual meeting:
      determinants of subsequent peer reviewed publication. C. C. Hoag, D. S. Elterman
      and A. E. MacNeily, J Urol 2006; 176: 2624-2629.

PMID- 17509376
TI  - Re: A multi-institution, minimally invasive urological oncology fellowship: a
      critical assessment of the clinical training and academic benefits. J. A. Brown
      and R. W. Lewis, J Urol 2006; 176: 2619-2623.

PMID- 17509381
TI  - Financial impact of obesity and bariatric surgery.
AB  - Obesity constitutes a major health problem with serious social and economic
      consequences worldwide. In North America, nearly one third of the population is
      obese, and this figure includes children and adolescents who are likely to become
      obese adults. Obesity carries a great financial impact on society; consequently,
      treating morbidly obese patients with surgery may offer substantial economic
      savings. This article summarizes the financial burdens of obesity and the
      economics of treating obesity in North America. It addresses the medical
      effectiveness and cost-effectiveness of bariatric surgery and the new regulations
      and accreditations for bariatric surgery programs.

PMID- 17509382
TI  - Preoperative assessment and perioperative care of patients undergoing bariatric
      surgery.
AB  - The prevalence of morbid obesity in the United States and worldwide is increasing
      at an alarming rate. The number of bariatric surgical procedures also has
      steadily increased during the past decade. This article reviews the published
      literature and current practice trends for preoperative workup and assessment of
      patients undergoing bariatric surgery.

PMID- 17509383
TI  - Bariatric surgery primer for the internist: keys to the surgical consultation.
AB  - The increasing prevalence of morbid obesity in North America combined with the
      refinement of laparoscopic techniques for the performing these operations has
      contributed to the exponential growth of bariatric surgery over the last 10
      years. There are many important considerations for the internist who is referring
      a patient for bariatric surgery.

PMID- 17509384
TI  - Management of the challenging bariatric surgical patient.
AB  - Despite the continued increase in surgical procedures for weight loss, the
      dramatic increase in the prevalence of morbid obesity far outpaces the treatments
      to correct it. As a result, the primary care physician is increasingly more
      likely to be evaluating patients who are either candidates for weight loss
      surgery or who have already undergone a weight loss procedure. Unique medical and
      social situations must be considered when evaluating these patients, and it is
      anticipated that all physicians will be seeing a greater number of complex or
      challenging patients.

PMID- 17509385
TI  - Metabolic aspects of bariatric surgery.
AB  - Insulin resistance is a nearly universal finding in morbid obesity. It may be
      compensated and latent or uncompensated with single or multiple clinical
      abnormalities. Although lifestyle interventions and medical measures alone may
      control most metabolic problems in the short term, the ultimate benefits of such
      an approach are usually limited by the complexity of available therapeutic
      regimens and the difficulty of maintaining full patient compliance. Many studies
      now document that bariatric surgery can effectively and safely control these
      complications in the short term and long term or even prevent their occurrence.
      Further investigations are needed to understand better the mechanisms involved
      and to define more clearly the appropriate indications and contraindications of
      the treatments proposed.

PMID- 17509386
TI  - Impact of obesity and bariatric surgery on cardiovascular disease.
AB  - Morbid obesity is a growing public health concern with multiple associated
      cardiovascular comorbidities. Bariatric surgery has emerged as a safe and
      effective treatment for morbidly obese patients at risk for, or already suffering
      from, cardiovascular disease. Weight loss induced by the surgery has been shown
      to improve cardiovascular risk factors, cardiac structure and function, and the
      clinical course of established cardiovascular disease. The role of adipocyte
      derived cytokines in mediating cardiovascular pathophysiology in obesity-and its
      modulation after weight loss-is under active investigation.

PMID- 17509387
TI  - Pulmonary considerations in obesity and the bariatric surgical patient.
AB  - Severe obesity can be associated with significant alterations in normal
      cardiopulmonary physiology. The pathophysiologic effects of obesity on a
      patient's pulmonary function are multiple and complex. The impact of obesity on
      morbidity and mortality are often underestimated. Bariatric surgery has been
      shown to be the most effective modality of reliable and durable treatment for
      severe obesity. Surgical weight loss improves and, in most cases, completely
      resolves the pulmonary health problems associated with obesity.

PMID- 17509388
TI  - Management of gastrointestinal disorders in the bariatric patient.
AB  - Morbid obesity continues to grow at an alarming rate. As of 2004, 35% of
      Americans were considered to have a body mass index (BMI) over 30. As the number
      of patients undergoing weight loss surgery increases, the patient population
      presenting to primary care physicians with previous gastric bypass will also
      increase. Accordingly, it will become imperative for primary care physicians to
      be familiar and comfortable with the care of these patients. This review focuses
      on the management of gastrointestinal disorders in postoperative gastric bypass
      patients.

PMID- 17509389
TI  - Psychosocial and behavioral status of patients undergoing bariatric surgery: what
      to expect before and after surgery.
AB  - Extreme obesity, characterized by a body mass index (BMI) of 40 kg/m(2) or
      greater, is associated with significantly increased mortality, principally from
      cardiovascular disease, type 2 diabetes, and several cancers. It also is
      associated with an increased risk of psychosocial complications, including
      depression, eating disorders, and impaired quality of life. This article briefly
      examines the psychosocial status of extremely obese individuals who seek
      bariatric surgery and describes changes in functioning that can be expected with
      surgically induced weight loss. The article combines a review of the literature
      with clinical impressions gained from the more than 2500 candidates for bariatric
      surgery whom the authors have evaluated at the Hospital of the University of
      Pennsylvania.

PMID- 17509390
TI  - Outpatient complications encountered following Roux-en-Y gastric bypass.
AB  - Practitioners taking care of postoperative bariatric patients need to keep in
      mind all of the complications that this population faces to prevent unnecessary
      morbidity. Bariatric patients presenting postoperatively with abdominal pain,
      tachycardia, vomiting, tachypnea, and a sense of impending doom should be worked
      up aggressively to find the cause of their symptoms. Because the incidence of
      obesity is rising in children and adults, more patients will have surgery to help
      with their weight loss. Physicians caring for these patients must be able to
      diagnosis and treat their complications quickly and efficiently to prevent
      further complications.

PMID- 17509391
TI  - Laparoscopic gastric band complications.
AB  - Weight loss surgery, also known as bariatric surgery, has evolved from a
      specialty dominated by intestinal bypasses and vertical banded gastroplasty to
      its current state of a specialty characterized by minimal access techniques and
      Centers of Excellence. Bariatric surgery has remained the only reliably effective
      option for significant weight loss for the morbidly obese. This article reviews
      common problems occurring after laparoscopic adjustable gastric band with
      emphasis on conservative diagnosis and effective treatment.

PMID- 17509392
TI  - Nutritional consequences of weight-loss surgery.
AB  - Nutritional deficiencies are already present in many morbidly obese patients
      before weight-loss surgery. Appropriate preoperative detection and correction is
      essential. The severity and pattern of deficiencies is dependent on the presence
      of preoperative uncorrected deficiency, the type of procedure performed varying
      with the degree of restriction or the length of bypassed small intestine, the
      modification of eating behavior, the development of complications, compliance
      with oral multivitamin and mineral supplementation, and compliance with follow
      up. Rigorous control of fluids and electrolytes with establishment of adequate
      oral nutrition is important in the immediate postoperative period. Regular follow
      up of the metabolic and nutritional status of the patient is essential, with life
      long multivitamin and mineral supplementation.

PMID- 17509393
TI  - Improvement in infertility and pregnancy outcomes after weight loss surgery.
AB  - The majority of bariatric surgical procedures are performed in young women. There
      is a concern about safety and outcomes of pregnancies after weight loss surgery.
      Pregnancy after weight loss surgery is not only safe, but is associated with more
      favorable outcomes in comparison to obese populations who do not undergo weight
      loss surgery. An interval of 2 years is recommended from surgery to pregnancy.
      This delay helps avoid most of the potential nutritional complications. Optimal
      patient care is achieved in an experienced, multidisciplinary center. Early
      involvement of the bariatric surgeon in evaluating abdominal pain is critical
      because the underlying pathology may relate to the previous weight loss surgery.
      Although infertility is improved after weight loss surgery, reliable modes of
      contraception may be limited in this population.

PMID- 17509394
TI  - Soft tissue tumors of the urinary bladder, Part I: myofibroblastic
      proliferations, benign neoplasms, and tumors of uncertain malignant potential.
AB  - Most bladder tumors arise from the urothelium. However, there are several
      uncommon but significant bladder lesions that must be differentiated from
      urothelial carcinomas. These include both benign and malignant spindle cell
      lesions. The first half of this 2-part review will describe benign
      myofibroblastic proliferations including inflammatory myofibroblastic tumor and
      postoperative spindle cell nodule; benign neoplasms including leiomyoma,
      hemangioma, neurofibroma, and schwannoma; and tumors of uncertain malignant
      potential including paraganglioma, granular cell tumor, and perivascular
      epithelioid cell tumor. Common clinical presentations, morphological
      characteristics, and immunohistochemical features are described to aid the
      practicing pathologist in the identification of these entities. This review also
      describes current theories as to the pathogenesis of inflammatory myofibroblastic
      tumor and postoperative spindle cell nodule and details the current molecular
      markers identifying several of these lesions.

PMID- 17509395
TI  - Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma with a complex
      karyotype and cryptic 3' ALK gene insertion to chromosome 4 q22-24.
AB  - Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL)
      is a rare tumor that is frequently associated with t(2;17)(p23;q23), a
      translocation fusing the ALK gene at 2p23 to the clathrin heavy chain gene (CLTC)
      at 17q23. Here, we report a unique case of ALK-positive DLBCL with plasmablastic
      morphology and focal cytoplasmic granular ALK stain in an HIV-negative 33-year
      old man. By conventional karyotyping, the lymphoma cells were near-tetraploid and
      included 4 structurally normal copies each of chromosomes 2 and 17. Fluorescence
      in situ hybridization revealed an apparently normal, intact ALK gene on each of
      the 4 chromosome 2 homologs plus a cytogenetically cryptic ALK gene insertion
      into 2 of the 4 chromosome 4 homologs at band 4q22-24. The lymphoma cells
      expressed CD138, lambda light chain, focal and weak CD30, and exhibited aberrant
      T-cell antigens, including perforin. This case indicates that ALK-positive DLBCL
      is more heterogeneous at the cytogenetic/molecular level than previously
      recognized.

PMID- 17509396
TI  - Primary monophasic synovial sarcoma of the duodenum with SYT/SSX2 type of
      translocation.
AB  - Recent findings on the molecular background of synovial sarcoma with the
      description of the specific translocation t(X;18) led to the incorporation of
      this particular genetic aberration into the definition of this tumor type.
      Synovial sarcomas with proven diagnostic translocation are being described with
      increasing frequency in unsuspected locations not related to joints, such as
      lung, pleura, heart, or pharynx. The gastrointestinal tract has been rarely
      reported as a primary site of synovial sarcomas with rare cases in the esophagus
      and stomach. We report a case of a primary synovial sarcoma of the distal
      duodenum with SYT/SSX2 type of the t(X;18) translocation. Primary spindle cell
      neoplasms of the duodenum are rare and consist mostly of gastrointestinal stromal
      tumors, which are amenable to the therapy with Gleevec. Synovial sarcoma widens
      the differential diagnosis of mesenchymal tumors of the intestine.

PMID- 17509397
TI  - Intracranial lesion of Erdheim-Chester disease.

PMID- 17509398
TI  - Langerhans cell component in bullous pemphigoid-like lesions associated with
      chronic lymphocytic leukemia.

PMID- 17509400
TI  - Innate immune responses of the dental pulp to caries.
AB  - Various cells and inflammatory mediators are involved in the initial pulpal
      responses to caries. This review focuses on the cellular, neuronal, and vascular
      components of pulpal innate responses to caries. Discussion will include dentinal
      fluid, odontoblasts, neuropeptides, and neurogenic inflammation, which are not
      classic immune components but actively participate in the inflammatory response
      as the caries progress pulpally. Summaries of innate immune cells as well as
      their cytokines and chemokines in healthy and reversible pulpitis tissues are
      presented.

PMID- 17509401
TI  - Redefining the persistent infection in root canals: possible role of biofilm
      communities.
AB  - Current concepts suggest that persisting infections subsequent to endodontic
      therapy are caused by one or two bacterial species that are "too robust" to be
      eliminated by conventional treatment measures. As a consequence, numerous studies
      are exploring the characteristics of these "most" resistant organisms to define
      an effective treatment strategy to eradicate them from root canals. By taking an
      ecological perspective, the main objective of this review is to present evidence
      that the nature of persisting endodontic infections depends not on the robustness
      of the organisms in the infected site, but on their capability of adapting their
      physiology to the new environmental conditions set by the treatment. Changes in
      the environment, such as an increase in pH by calcium hydroxide or the effect of
      antimicrobials, are capable of triggering genetic cascades that modify the
      physiological characteristics of bacterial cells. Surface adherence by bacteria
      to form biofilms is a good example of bacterial adaptation and one that is
      pertinent to endodontic infections. Increasing information is now available on
      the existence of polymicrobial biofilm communities on root canal walls, coupled
      with new data showing that the adaptive mechanisms of bacteria in these biofilms
      are significantly augmented for increased survival. This ecological view on the
      persisting infection problem in endodontics suggests that the action of
      individual species in persisting endodontic infections is secondary when compared
      to the adaptive changes of a polymicrobial biofilm community undergoing
      physiological and genetic changes in response to changes in the root canal
      environment.

PMID- 17509402
TI  - The development of a diagnostic instrument for the measurement of mechanical
      allodynia.
AB  - Mechanical allodynia, defined as a reduction in mechanical pain threshold, is an
      essential diagnostic feature of inflammation of the periodontal ligament.
      Traditional methods for measuring mechanical allodynia in a tooth are not
      quantitative. This study evaluated the reliability of a new bite force transducer
      to measure mechanical pain thresholds, which might have application as a
      quantitative diagnostic aid for measuring mechanical allodynia in patients with
      apical periodontitis. To determine inter-observer reliability, subjects (n = 40)
      were given standardized instructions before generating maximal bite force on
      maxillary first molars; readings were then recorded by three examiners for a
      total of ten readings per examiner. To determine the test-retest reliability, the
      initial examiner then retested at two different sessions. The intraclass
      correlation coefficient was fair to substantial for inter-observer reliability
      (0.3-0.64) and substantial for intra-observer reliability (0.63-0.68). Thus, the
      force transducer used in our study is a reliable method to measure mechanical
      pain thresholds in endodontic patients.

PMID- 17509403
TI  - Bacterial reduction in infected root canals treated with 2.5% NaOCl as an
      irrigant and calcium hydroxide/camphorated paramonochlorophenol paste as an
      intracanal dressing.
AB  - This clinical study investigated the bacterial reduction after instrumentation
      using 2.5% sodium hypochlorite (NaOCl) as an irrigant and further
      interappointment dressing with a calcium hydroxide (Ca(OH)(2))/camphorated
      paramonochlorophenol (CPMC) paste. Eleven teeth with primary intraradicular
      infections and chronic apical periodontitis selected according to stringent
      inclusion/exclusion criteria followed in the study. Bacterial samples were taken
      before treatment (S1), after chemomechanical preparation using hand NiTi files
      and 2.5% NaOCl (S2), and following a 7-day medication with a Ca(OH)(2) paste in
      CPMC (S3). Cultivable bacteria recovered from infected root canals at the three
      stages were counted and identified by means of 16S rRNA gene sequencing analysis.
      At S1, all cases harbored bacteria, with a mean number of 2.8 taxa per canal
      (range, 1-6). At S2, 6 of 11 (54.5%) of the cases yielded positive cultures, with
      one to three species per canal. At S3, only one case (9.1%) was positive for the
      presence of bacteria, with Propionibacterium acnes as the only taxon isolated. A
      significantly high reduction in bacterial counts was observed between S1 and S2,
      and S1 and S3. Significant differences were also observed for comparisons
      involving S2 and S3 samples with regard to both quantitative bacterial reduction
      (p = 0.029) and number of culture-negative cases (p = 0.03). It was concluded
      that chemomechanical preparation with 2.5% NaOCl as an irrigant significantly
      reduced the number of bacteria in the canal but failed to render the canal free
      of cultivable bacteria in more than one-half of the cases. A 7-day intracanal
      dressing with Ca(OH)(2)/CPMC paste further significantly increased the number of
      culture-negative cases.

PMID- 17509404
TI  - Microbial leakage of Enterococcus faecalis after post space preparation in teeth
      filled in vivo with RealSeal versus Gutta-percha.
AB  - The purpose of this study was to compare microbial leakage of Enterococcus
      faecalis after post space preparation in teeth filled in vivo with RealSeal
      (SybronEndo, Orange, CA) versus gutta percha. Twenty-six premolars in which
      extraction was indicated for orthodontic reasons were endodontically treated
      before extraction to simulate normal clinical conditions. Ten of these bicuspids
      were obturated following the RealSeal protocol; the other 10 were filled with
      gutta percha and Grossman-based formula cement. Post space was prepared
      immediately after filling leaving 5 mm of apical obturation material. The rest of
      the teeth were equally divided into the positive and negative control groups.
      Forty-eight hours later teeth were extracted and submitted to a dual-chamber
      leakage model using E faecalis. All of the RealSeal-filled teeth showed leakage
      during the first week, having a mean leakage of 3.5 days (+/-2.32 days). Gutta
      percha-filled teeth showed a mean leakage of 10 days (+/-11.53 days). Mann
      Whitney U comparison between groups revealed a p = 0.09. Under the conditions of
      the present study, there is no statistically significant difference in the
      microleakage of teeth filled with RealSeal compared with gutta percha when post
      space is prepared.

PMID- 17509405
TI  - Clinical and radiographical evaluation of a resin-based root canal sealer: a 5
      year follow-up.
AB  - A retrospective clinical and radiographical analysis of 5-year postendodontic
      treatment with a resin-based sealer (EndoRez; Ultradent Products Inc, South
      Jordan, UT) and gutta-percha was conducted. The results after 14 to 24 months
      were reported previously. Of 180 patients, 120 responded to the 5-year recall.
      Success of root canal treatments was based on absence of clinical symptoms, a
      normal or slightly widened periodontal ligament, and absence or reduction of
      periapical radiolucencies in patients who had preexisting lesions. Root canals
      had been adequately filled to the working length in 92 teeth (76.66%) and short
      in 13 (10.83%). Fifteen cases (12.50%), filled flush at the initiation of the
      experiment, showed slight resorption of the filling material at the apex within
      the lumen of the root canal. Of the 10 roots with extrusion, none had
      radiographic evidence of sealer in the periradicular tissues after 5 years. All
      patients were free of clinical symptoms. Four cases (3.3%) showed partial
      healing, whereas 8 cases (6.66%) were judged failures. A life table analysis
      revealed a cumulative probability of success of 86.3% at the 5-year recall with a
      95% confidence interval of 79.7 to 91.0. The clinical and radiographical data
      suggest that the tested resin-based sealer used in conjunction with gutta-percha
      performed very well as a root canal sealer over a period of up to 5 years.

PMID- 17509406
TI  - Pulp revascularization of immature dog teeth with apical periodontitis.
AB  - This study examined the ability of a collagen solution to aid revascularization
      of necrotic-infected root canals in immature dog teeth. Sixty immature teeth from
      6 dogs were infected, disinfected, and randomized into experimental groups: 1: no
      further treatment; 2: blood in canal; 3: collagen solution in canal, 4: collagen
      solution + blood, and 5: negative controls (left for natural development).
      Uncorrected chi-square analysis of radiographic results showed no statistical
      differences (p >or= 0.05) between experimental groups regarding healing of
      radiolucencies but a borderline statistical difference (p = 0.058) for group 1
      versus group 4 for radicular thickening. Group 2 showed significantly more apical
      closure than group 1 (p = 0.03) and a borderline statistical difference (p =
      0.051) for group 3 versus group 1. Uncorrected chi-square analysis revealed that
      there were no statistical differences between experimental groups for
      histological results. However, some roots in each of groups 1 to 4 (previously
      infected) showed positive histologic outcomes (thickened walls in 43.9%, apical
      closure in 54.9%, and new luminal tissue in 29.3%). Revascularization of
      disinfected immature dog root canal systems is possible.

PMID- 17509407
TI  - Molecular- and culture-based comparison of the effects of antimicrobial agents on
      bacterial survival in infected dentinal tubules.
AB  - The aim of this study was to evaluate the effect of root canal obturation with or
      without prior calcium hydroxide (Ca(OH)(2)) or 2% chlorhexidine (CHX) on the
      persistence of bacteria or its DNA in infected dentinal tubules. Canals of 85
      extracted teeth were instrumented and inoculated with 10(4) cells/mL of
      Enterococcus faecalis. Teeth were incubated at 37 degrees C for 21 days and
      divided into 3 groups of 25 teeth plus controls. Teeth in group 1 were obturated
      immediately with gutta-percha (GP) and AH-Plus (Maillefer, Dentsply, Tulsa, OK).
      In group 2, Ca(OH)(2) was placed for 7 days before obturation. In group 3, 10
      minutes of irrigation was performed with CHX performed before obturation. After
      incubation, GP was removed, and dentin specimens were collected and analyzed with
      culturing and polymerase chain reaction (PCR). No growth occurred in any
      cultures. By using PCR, E faecalis was detected in fewer roots in group 3 than in
      groups 1 or 2 (chi(2), p = 0.05); 2% CHX treatment followed by obturation was
      more effective in removing E faecalis DNA than placement of Ca(OH)(2) or
      immediate obturation.

PMID- 17509408
TI  - Influence of the type of vehicle and limit of obturation on apical and periapical
      tissue response in dogs' teeth after root canal filling with mineral trioxide
      aggregate.
AB  - The purpose of this study was to investigate the influence of the type of vehicle
      (distilled water or propyleneglycol) on the response of apical tissues of dogs'
      teeth after root canal filling with mineral trioxide aggregate (MTA) at two
      different limits. Forty roots of incisors and premolars of two adult dogs were
      used. After pulpectomy, the root canals were prepared biomechanically, and the
      roots had the apical cemental barrier penetrated with a #15 K-file and widened to
      a #25 K-file. The root canals were assigned to four groups according to the
      vehicle used for MTA (ProRoot-MTA; Tulsa Dental, Tulsa, OK) preparation and the
      limit of root canal filling: group 1, filling with MTA/distilled water to the
      limit of the cemental canal; group 2, overfilling with MTA/distilled water; group
      3, filling with MTA/propyleneglycol to the limit of the cemental canal; and group
      4, overfilling with MTA/propyleneglycol. The animals were killed by anesthetic
      overdose 90 days after endodontic treatment, and the anatomic pieces were
      prepared for histomorphological analysis. The sections were stained with
      hematoxylin and eosin and Brown and Brenn techniques. The results showed that MTA
      pastes prepared with either distilled water or propyleneglycol as vehicles had
      similar biological behavior (p > 0.05); root fillings placed at the cemental
      canal limit showed better results than the overfillings (p = 0.01), and
      MTA/propyleneglycol paste was more easily placed into the root canals than
      MTA/distilled water paste.

PMID- 17509409
TI  - Eugenol suppressed the expression of lipopolysaccharide-induced proinflammatory
      mediators in human macrophages.
AB  - Eugenol is commonly used as an analgesic agent during acute pulpitis and is a
      major component of root canal sealers. Despite the frequent applications of
      eugenol in the practice of dentistry, little is known about the role of eugenol
      under the status of inflammation. This study was aimed to investigate the
      influence of eugenol on human macrophages (U937) under the stimulation of
      lipopolysaccharide (LPS). Eugenol was shown to block the release of the bone
      resorbing mediators, including interleukin-1beta (IL-1beta), tumor necrosis
      factor-alpha (TNF-alpha), and prostaglandin E2 from LPS-stimulated macrophages.
      In contrast, eugenol alone did not alter the expression levels of these
      proinflammatory mediators in macrophages. Consistent with downregulation of bone
      resorbing mediators, eugenol suppressed the messenger RNA expression of LPS
      induced IL-1beta, TNF-alpha, and cyclooxygenase-2 in macrophages. The results
      suggest a potential anti-inflammatory effect of eugenol in the acute inflamed
      pulps and apical periodontitis.

PMID- 17509410
TI  - Expression of mineralization markers in dental pulp cells.
AB  - There is an increasing interest in the utility of dental pulp stem cells (DPSCs)
      for dentin regeneration. The mechanisms involved in DPSC differentiation remain
      poorly understood. The purpose of the study was to investigate the mineralization
      capacity of human dental pulp cells (DPCs) and identify potential markers for
      odontoblast differentiation. The isolated DPCs expressed mesenchymal stem-cell
      markers as shown by flow cytometry and could differentiate in vitro into
      odontogenic, adipogenic, and chondrogenic lineages. Alkaline phosphatase activity
      of DPCs elevated over time, with significant upregulation on day 21 in
      odontogenic induction. Quantitative RT-PCR revealed that osteocalcin, dentin
      sialophosphoprotein (DSPP), and matrix extracellular phosphoglycoprotein (MEPE)
      expression also increased time dependently in the induction cultures. In
      conclusion, we isolated DPCs with stem cell characteristics. MEPE and DSPP showed
      a similar regulatory pattern of DPCs mineralization. MEPE along with DSPP may be
      potential odontogenetic differentiation markers.

PMID- 17509411
TI  - Correlation between platelet-derived growth factor B chain and bone resorption in
      rat periapical lesions.
AB  - The purpose of this study was to examine the relationship between platelet
      derived growth factor B chain (PDGF-B) and bone resorption in rat periapical
      lesions. Periapical lesions were induced in Sprague-Dawley rats by occlusal
      exposure of the pulp of their mandibular first molars. Animals were sacrificed
      randomly at 0, 7, 14, 21, and 28 days after the exposure, and frontal sections
      were prepared for immunohistochemistry and enzymehistochemistry. PDGF-B-positive
      cells and osteoclasts could be observed on day 7. From day 7 to day 14, the
      number of PDGF-B-positive cells and osteoclasts were ascending, and a significant
      correlation was found between them; from day 21 to day 28, more PDGF-B-positive
      cells and fewer osteoclasts could be observed, and the positive expression of
      PDGF-B was negatively correlated with osteoclasts. These findings showed that
      PDGF-B could be observed, which might be associated with the bone resorption of
      periapical lesions.

PMID- 17509412
TI  - A scanning electron microscopy evaluation of microfractures, deformation and
      separation in EndoSequence and Profile nickel-titanium rotary files using an
      extracted molar tooth model.
AB  - The development of microfractures in the EndoSequence nickel-titanium rotary
      (NTR) file (Brassler USA, Savannah, GA) and Profile NTR file was evaluated by
      using scanning electron microscopy (SEM). Seventy-three maxillary buccal roots
      and 53 mandibular mesial roots with an average canal curvature of 37 degrees were
      randomly assigned to one of three groups and prepared with 21-mm .06 taper NTR
      files as follows: (1) EndoSequence at 300 rpm, (2) EndoSequence at 600 rpm, and
      (3) ProFile at 300 rpm. File sizes .45 to .20 were used in a crown-down technique
      to a master apical file (MAF) size of .35/.06. The MAF instruments were evaluated
      by SEM before use, after completion of 7 canals, and after completion of 14
      canals. All EndoSequence instruments developed microfractures by the seven-canal
      evaluation. The ProFile instruments showed no microfractures at the 7- or 14
      canal evaluations. EndoSequence files separated at a higher rate than ProFile
      instruments. Under the conditions of this study, unique file design and
      electropolishing did not inhibit the development of microfractures in
      EndoSequence NTR.

PMID- 17509413
TI  - Evaluation of chlorhexidine toxicity injected in the paw of mice and added to
      cultured l929 fibroblasts.
AB  - Because chlorhexidine (CHX) has been recommended as either an endodontic irrigant
      or root canal dressing, this study aimed to characterize, in vivo, the lesion
      induced by injections of CHX in the paw of mice at selected time intervals (24
      and 48 hours and 7 and 14 days) and, in vitro, the mode of cell death, necrosis
      and/or apoptosis, and the cellular stress caused by exposition of cultured L929
      fibroblasts to ascending concentrations of CHX for 24 hours. CHX injected in the
      subplantar space of the hind paw of mice induced severe toxic effects, as
      evidenced by necrotic changes in the epidermis, dermis, and subcutaneous tissue
      in association with reactive inflammatory response, particularly at higher
      concentrations. In addition, in cultured fibroblasts, CHX induced apoptosis at
      lower concentrations and necrosis at higher concentrations and increased
      expression of heat-shock protein 70, an indicator of cellular stress. Taken
      together, these findings suggest that CHX may have an unfavorable effect on the
      resolution of apical periodontitis.

PMID- 17509414
TI  - Comparative analysis of endodontic pathfinders.
AB  - Because no scientific literature exists regarding endodontic pathfinders, the aim
      of this study was to compare such instruments. Ten different pathfinder-type
      files were analyzed with respect to dimensional characteristics, pitch, and
      rigidity; efficiency, wear, and distortion were assessed by using an in vitro
      simulation exercise. SEM cross-sections and tip images were obtained and
      analyzed. To assess efficacy and distortion, 10 operators attempted to achieve
      patency with the files in small, S-shaped canals in acrylic blocks. Trends in
      canal negotiation efficiency and file distortion were recorded. Results showed
      that the Hi-5 (Miltex, York, PA) and C+ files (Dentsply/Maillefer, Johnson City,
      TN) were the least flexible, whereas the Pathfinder CS (SybronEndo, Glendora, CA)
      and Pathfinder SS (SybronEndo) files were the most. Pathfinder SS, S finder
      (JSDental/Sendoline, Ridgefield, CT), and D finder (Mani, Tochigi-ken, Japan)
      were the most efficient during the simulation exercise. Within the parameters of
      this study, pitch, taper, cross-section, heat tempering, metal type, tip
      geometry, and operator skills all influenced pathfinder efficiency.

PMID- 17509415
TI  - Development of a finite element analysis model with curved canal and stress
      analysis.
AB  - This study aimed to establish a model of a curved canal by finite element
      analysis (FEA). To develop a repeatable and comparable model, simulated curved
      canals with uniform shape were selected as prototype canals, and a suitable
      extracted single-root tooth was chosen as the outline. Subsequent combinations
      and modifications were performed by using the analysis program ABAQUS. By using a
      series of imitational occlusive forces loaded onto the incisive edge of the
      model, color plots and the maximal stresses at the apical region were analyzed.
      Stresses increased when the angle of the loads rose, and loads in the distal and
      mesial directions induced more stresses in the target region than did loads in
      the buccal and lingual directions. This study has established a standardized FEA
      model with a curved canal. Consequently, this model may be applied for future
      estimations in endodontic procedures for a curved canal.

PMID- 17509416
TI  - Effect of new obturating materials on vertical root fracture resistance of
      endodontically treated teeth.
AB  - The aim of this study was to compare vertical forces at fracture of teeth
      obturated with different materials. Single-rooted teeth were divided into five
      groups. The first group served as a negative control. The remaining four groups
      were shaped using ProTaper rotary files (Dentsply Maillefer, Ballaigues,
      Switzerland). The second group was obturated with gutta percha and a zinc oxide
      sealer. The third group was obturated with EndoRez points and EndoRez sealer
      (both from Ultradent, South Jordan, UT). The fourth group was obturated with
      Resilon (Pentron Clinical Technologies, Wallingford, CT) and RealSeal sealer
      (Pentron Clinical Technologies). The fifth group was obturated with Guttaflow
      (Coltene/Whaledent, Altstatten, Switzerland). Roots were then fixed into a
      universal testing machine and loaded with a spreader until fracture. It was found
      that forces at fracture were statistically significantly higher in the Resilon
      and EndoRez groups. It was concluded that obturation of roots with resin-based
      obturation materials (Resilon and EndoRez) increased the resistance of root canal
      filled teeth to vertical root fracture.

PMID- 17509417
TI  - Effect of clinical use on the cyclic fatigue resistance of ProTaper nickel
      titanium rotary instruments.
AB  - The resistance of ProTaper (Dentsply Maillefer, Ballaigues, Switzerland) nickel
      titanium rotary instruments to cyclic fatigue was examined after their initial
      use in straight or curved canals in vivo. These instruments were rotated freely
      inside a steel phantom until separation. The number of rotations before failure
      and the lengths of the separated fragments were compared with data derived from
      new instruments under the same experimental setup (n = 20). With the exception of
      F1 and F3, instruments previously used in curved canals were more susceptible to
      cyclic fatigue than those previously used in straight canals (p < 0.05).
      Separation occurred predominantly at the D10 to D12 level. For the F series, a
      negative correlation (p < 0.05) was observed between the number of rotations
      before failure and the file diameters at their separation levels. ProTaper F3
      instruments are highly susceptible to cyclic fatigue failure and should be reused
      with caution irrespective of whether they are initially used for shaping straight
      or curved canals.

PMID- 17509418
TI  - New tetrasilicate cements as retrograde filling material: an in vitro study on
      fluid penetration.
AB  - We aimed to compare the apical sealing ability of two experimental retrograde
      root-filling cements and mineral trioxide aggregate using a fluid filtration
      method. X-ray diffraction (XRD) and X-ray fluorescence spectrometry (XRF) were
      used to evaluate structural and qualitative characteristics. Thirty single-rooted
      extracted teeth were treated, root-end prepared, and obturated using MTA and two
      experimental cements. Fluid filtration was measured during a 5-minute period
      after 4, 24, and 48 hours and 1, 2, and 12 weeks. The results were statistically
      compared by using a two-way analysis of variance (p < 0.05). The marginal
      adaptation was evaluated by using a SEM replica technique. XRD analyses showed
      similar patterns. XRF showed lower amounts of SiO(2) and FeO(3) in the
      experimental cements. All cements showed a reduced fluid flow rate over time. No
      significant differences were found between the cements. The SEM replica indicated
      a good marginal adaptation to dentinal walls. Both experimental cements showed
      suitable properties as retrograde root-filling materials.

PMID- 17509419
TI  - Influence of irrigating needle-tip designs in removing bacteria inoculated into
      instrumented root canals measured using single-tube luminometer.
AB  - This study tested the mechanical efficacy of various irrigating needle tip
      designs on bacteria inoculated into instrumented root canals. Root canals of 30
      extracted permanent canines were prepared to size 60 at working length (WL) using
      ProFile 0.04 taper rotary nickel-titanium files. Root canals were autoclaved and
      inoculated with a 20-microl suspension (1.4 x 10(7) cells) of genetically
      engineered Escherichia coli pYUB556. Bioluminescence was measured before
      inoculation (baseline), after inoculation and after irrigation with 6 ml of
      saline using luminometer. Safety-ended needles with single (group 1) and double
      (group 2) side-port and hypodermic needles (group 3) were used upto 1 mm short of
      WL. The percentage of bacteria remaining after irrigation was 67.9 +/- 9.5, 75.3
      +/- 12.9 and 77.7 +/- 11.8 respectively (p < 0.05; Kruskal-Wallis) with no
      difference between group II and group III (p > 0.05; Mann-Whitney). Irrigation
      using safety needles with single side port was significantly effective.

PMID- 17509420
TI  - A comparison of gutta-percha and Resilon in the obturation of lateral grooves and
      depressions.
AB  - The purpose of this study was to compare the flow of gutta-percha and Resilon
      (RealSeal; SybronEndo, Orange, CA) into lateral grooves and depressions in the
      apical 7 mm of a root canal by using warm vertical compaction. A split-tooth
      model was constructed with lateral grooves and depressions prepared at 1, 3, 5,
      and 7 mm from working length (WL). Groups A, B, and C were obturated with gutta
      percha with a System B plugger placed 5 mm, 4 mm, and 3 mm from WL. Groups D, E,
      and F were obturated with Resilon with a System B plugger placed 5 mm, 4 mm, or 3
      mm from WL. Gutta-percha and Resilon showed similar movement into lateral grooves
      and dentin depressions, with a significant difference found only with increased
      flow of gutta-percha into depressions at the 1-mm level when the System B plugger
      was placed 3 mm or 4 mm from WL (p <or= 0.05).

PMID- 17509421
TI  - Conventional endodontic therapy of upper central incisor combined with cyst
      decompression: a case report.
AB  - Treatment of a maxillary central incisor with an associated cystic lesion by
      conventional endodontic therapy combined with decompression is reported. Although
      small cystic lesions frequently heal simply with endodontic therapy, larger
      lesions may need additional treatment. If surgical enucleation is elected, other
      teeth or structures may be damaged unnecessarily. Therefore, a case can be made
      for first attempting the more conservative treatment of decompression, and a
      workable protocol for this is presented. In this case, 6 weeks with latex tubing
      in place and daily irrigation with 0.12% chlorhexidine led to complete healing
      with no need for further surgery or other root canal therapy on teeth initially
      surrounded by this lesion. At the 2-year recall, the lesion has completely
      resolved, and the adjacent teeth remain vital and normal.

PMID- 17509422
TI  - An aiming device for an extraoral radiographic technique.
AB  - To assist certain patient populations who are unable to tolerate intraoral films
      and/or sensors during endodontic therapy, an alternative technique (extraoral
      film placement) has been innovated by Newman and Friedman (2003). In this study,
      we devise and test a film/sensor-beam alignment aiming device for taking a
      periapical radiograph using this extraoral radiographic technique. An instrument
      is assembled from the following components: (1) two locator rings for bite-wing
      radiography, (2) two metal supporting indicator rods for bite-wing radiography,
      (3) a bite block for horizontal bite-wing radiography, and (4) a rubber tube of
      about 2 cm in length. Using our newly-devised aiming device to take periapical
      radiographs using the extraoral technique, appropriate images of the left upper
      and right lower molar areas for a series of 12 adult volunteers were successfully
      obtained. Angulation of the x-ray cone, with reference to the horizontal plane,
      was -20 degrees to -30 degrees and -10 degrees to -15 degrees for the upper and
      lower teeth, respectively. This study therefore shows that appropriate images can
      be easily obtained using this aiming device.

PMID- 17509423
TI  - A telephone-delivered empowerment intervention with patients diagnosed with heart
      failure.
AB  - BACKGROUND: Heart failure (HF) is a major public health problem. Case management
      by nurses using telephone follow-up has been suggested as a convenient and
      effective mechanism to promote the self-management of HF. Similarly, a patient
      empowerment approach to the management of chronic disease has been suggested as
      one that may nurture self-management in individuals with chronic illness.
      OBJECTIVE: The purpose of this study was to examine the effects of a telephone
      delivered empowerment intervention (EI) on clinically and theoretically relevant
      outcomes in patients with HF, including purposeful participation in goal
      attainment, self-management of HF, and perception of functional health. The EI
      was guided by Rogers' Science of Unitary Human Beings person-environment process.
      METHODS: A convenience sample of men and women aged 21 years and older with a
      clinical diagnosis of HF was obtained from a metropolitan hospital located in the
      southwestern United States. The participants were randomly assigned to the
      control group (n = 45) or EI group (n = 45). All participants received
      standardized HF patient education; the intervention group also received an EI
      delivered through telephone follow-up calls from a registered nurse. Repeated
      measures analysis of variance was used to evaluate intervention effects. RESULTS:
      The telephone-delivered EI facilitated self-management of HF through self-care
      activities in EI group members. CONCLUSION: The knowledge gained from this study
      provides a beginning understanding of strategies to enhance health care
      providers' ability to facilitate self-management of HF among patients diagnosed
      with HF.

PMID- 17509424
TI  - Caregiver burden and outcomes of caregiving of spouses of patients who undergo
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Patients who undergo coronary artery bypass graft surgery often rely
      on spouses for care during recovery. Although often meaningful, caregiving may be
      stressful and affect spouses' ability to provide care to the patient. OBJECTIVES:
      The purpose of this study was to compare burden and caregiving outcomes across
      three groups of spouses. Spouse groups varied by the interval of time between
      surgery and follow-up, which may have been 3, 6, or 12 months. METHODS: This
      cross-sectional comparative study recruited a convenience sample of 166 spouses
      on the basis of a power analysis. A total of 166 spouses completed caregiver
      surveys on burden and other caregiving outcomes. RESULTS: Total, objective, and
      subjective burden levels were low to moderate. Although no burden differences
      were found between groups, men had higher total burden but more positive
      caregiving outcomes. Future outlook and social activities were less positive in
      the 6-month group. Burden levels were not lower, nor were caregiving outcomes
      higher, in the 12-month group, suggesting a steady caregiving demand across the
      first year after coronary artery bypass graft surgery. CONCLUSION: Longitudinal
      investigations are needed to understand burden and caregiving outcomes over time
      and the impact of burden on spousal and patient recovery outcomes.

PMID- 17509425
TI  - Comparison of forehead and digit oximetry in surgical/trauma patients at risk for
      decreased peripheral perfusion.
AB  - OBJECTIVE: Measurement of pulse oximetry (Spo(2)) is often impaired in critically
      ill patients. Forehead reflectance oximetry, the Max-Fast (Nellcor, Pleasanton,
      CA), may be less susceptible to poor tissue perfusion and could improve accuracy
      of oxygen saturation measurement. The objective of this study was to evaluate the
      use of forehead oximetry measures in critically ill surgical/trauma patients.
      METHODS: A prospective interventional study of 30 critically ill surgical/trauma
      patients at risk for decreased peripheral perfusion, as evidenced by need for
      vasopressor support (24 patients), transfusion of more than 6 unit packed cells
      in 24 hours (two patients), or an inability to obtain consistent saturation from
      a digit sensor (four patients), compared forehead and digit-based oximeter Spo(2)
      readings with co-oximetry (Sao(2)) measurements from arterial blood samples.
      Sao(2) values were converted to functional oxygen saturation (SO(2)) measurements
      for the final comparison. Patients were fitted with forehead (Nellcor Max-Fast)
      and digit (Nellcor Max A; digit 1) sensors connected to Nellcor OxiMax N-595
      oximeters and a digit sensor (Nellcor Max A; digit 2) connected to a
      multiparameter monitor (Philips CMS [Andover, MA]). Three measurements of Sao(2)
      were obtained from each subject over a 24-hour time period, and simultaneous
      measurements of Spo(2) were recorded from the three monitors. RESULTS: The three
      Spo(2) measurements (forehead, digit 1, and digit 2) were compared with SO(2)
      values using the Bland-Altman method to assess agreement. Forehead measurements
      demonstrated a mean bias of -1.39, whereas digit 1 was -2.61 and digit 2 was 
      3.84. Pearson correlations (r) for forehead, digit 1, and digit 2 with SO(2) were
      .834, .433, and .254, respectively. There were fewer unsuccessful measurements
      with the forehead oximetry technique. CONCLUSIONS: Forehead sensors improve
      measurement of oxygen saturation in critically ill surgical/trauma patients at
      risk for decreased peripheral perfusion.

PMID- 17509427
TI  - Reliability and validity of the Exercise Self-Regulatory Efficacy Scale for
      individuals with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Exercise has important benefits for individuals with chronic
      obstructive pulmonary disease (COPD). However, to sustain long-term benefits of
      exercise, adherence is needed. Adherence requires self-regulation. No scale is
      available to measure exercise self-regulation in individuals with COPD.
      OBJECTIVES: We developed and tested the reliability and validity of an "Exercise
      Self-Regulatory Efficacy Scale (Ex-SRES)" for individuals with COPD. METHODS: A
      convenience sample of 109 subjects with COPD was recruited. Cronbach's alpha was
      used to assess the internal consistency reliability of the Ex-SRES. Subjects'
      exercise behaviors and health status were used to assess the validity of the Ex
      SRES. RESULTS: The Ex-SRES demonstrated evidence of reliability (Cronbach's alpha
      .917) and validity (correlation with minutes of exercise per week [r = .41; P <
      .0001] and health status [r = .37; P < .0001]). CONCLUSION: The Ex-SRES is a
      short (16-items) and easy to use questionnaire that may be valuable for assessing
      patients in clinical settings, as well as for future research studies in
      behaviors related to exercise.

PMID- 17509426
TI  - Efficacy of N-acetylcysteine and hydration versus placebo and hydration in
      decreasing contrast-induced renal dysfunction in patients undergoing coronary
      angiography with or without concomitant percutaneous coronary intervention.
AB  - OBJECTIVE: Contrast-induced renal dysfunction is an iatrogenic complication that
      occurs more frequently in patients with preexisting renal dysfunction. A
      prospective, double-blind, randomized, placebo, controlled trial was completed to
      assess the efficacy of N-acetylcysteine in decreasing the incidence of contrast
      induced renal dysfunction in patients with an acute coronary syndrome and renal
      insufficiency who underwent coronary angiography with or without percutaneous
      coronary intervention. METHODS: With similar intravenous hydration protocols, 20
      patients received N-acetylcysteine (treatment group) and 20 patients received
      placebo (control group) in a twice per day dosing regimen with one dose before
      and three doses after contrast media exposure. RESULTS: The two groups were
      similar at baseline on demographic and clinical characteristics, and preexisting
      renal insufficiency. Contrast-induced renal dysfunction, defined as an increase
      in serum creatinine greater than 44 micromol/L (.5 mg/dL) and/or 25% above
      baseline within 48 hours, occurred in 7.5% of the cohort, with 2.5% in the
      treatment group, and 5% in the control group, for an absolute difference of 2.5%.
      There was no difference in serum creatinine or creatinine clearance at 24 hours
      or at 48 hours between the treatment and control groups. CONCLUSION: These
      results suggest that this cohort gained no added protection to renal function
      with the use of N-acetylcysteine.

PMID- 17509428
TI  - Diagnostic blood loss in mechanically ventilated patients.
AB  - BACKGROUND: Concern for the volume of blood loss resulting from diagnostic
      phlebotomy has been expressed in the literature for decades. Blood conservation
      strategies have been found to reduce the volume withdrawn for laboratory tests,
      but some patient populations may remain at risk. OBJECTIVE: This study examines
      the frequency of phlebotomy and volume of diagnostic blood loss for critically
      ill mechanically ventilated patients in a small community hospital. METHODS: The
      subjects were 43 critically ill adults who received mechanical ventilation for at
      least 24 hours during the first quarter of 2005. Data were collected from
      computerized medical records and included the frequency and types of laboratory
      tests performed over the course of hospitalization. RESULTS: The mean total
      number of blood samples withdrawn was 69 (standard deviation = 59). The mean
      amount withdrawn per day was 16 mL (standard deviation = 7) with mean total
      volumes ranging from 57 to 1120 mL per patient. Four patients had more than 500
      mL withdrawn. Chemistry analyses accounted for both the highest frequency of
      phlebotomy and the highest volume. CONCLUSIONS: The daily volume of diagnostic
      blood loss for this population was less than the amounts previously reported in
      the literature, so there is some evidence of effectiveness of blood conservation
      strategies. However, some patients were still experiencing blood loss as the
      result of phlebotomy that may have been clinically significant. Additional
      strategies for reducing phlebotomy volumes are recommended.

PMID- 17509429
TI  - Atypical mediastinal lipomatosis.
AB  - We present an elderly, non-obese male with no significant medical history who
      presented with dyspnea on exertion. Chest radiography showed an enlarged cardiac
      silhouette with a retrocardiac shadow of increased lucency, resulting in a
      "double contour" effect. Transthoracic echocardiography raised the suspicion of a
      diffuse fatty infiltration in the pericardium severely distorting the left
      atrium. This was later confirmed on computed tomography of the chest by measuring
      radiodensity in Hounsfield units. The serum cortisol level ordered later was
      normal. To the authors' knowledge, this is only the second reported case of
      mediastinal lipomatosis that occurred in the absence of endogenous or exogenous
      steroid excess or obesity, with diffuse fatty infiltration, suspected on chest
      radiography and transthoracic echocardiography and confirmed by computed
      tomography of the chest.

PMID- 17509430
TI  - Listeria monocytogenes encephalitis mimicking Herpes Simplex virus encephalitis:
      the differential diagnostic importance of cerebrospinal fluid lactic acid levels.
AB  - Listeria monocytogenes is a common cause of bacterial meningitis in elderly
      patients and in those with impaired cellular immunity. The most common central
      nervous system infection caused by L. monocytogenes is acute bacterial
      meningitis; meningoencephalitis is uncommon and encephalitis is rare. Early
      diagnosis of L. monocytogenes meningitis is difficult because only 50% of
      cerebrospinal fluid (CSF) Gram stains are negative. L. monocytogenes is one of
      the few central nervous system pathogens associated with red blood cells in the
      CSF. When L. monocytogenes presents as encephalitis with red blood cells in the
      CSF, the clinical presentation mimics most closely herpes simplex virus (HSV)-1
      encephalitis. Because the therapies for L. monocytogenes and HSV-1 are different,
      early diagnostic differentiation is clinically important. The CSF lactic acid is
      the best way to rapidly differentiate between these two entities; the CSF lactic
      acid level is elevated in L. monocytogenes but is not elevated in HSV-1
      encephalitis. The case presented is an elderly man with chronic lymphocytic
      leukemia who presented with encephalitis. Advanced age and chronic lymphocytic
      leukemia predispose him to a wide variety of pathogens, but the rapidity and
      severity of his clinical presentation made L. monocytogenes and HSV-1
      encephalitis the most likely diagnostic possibilities. The CSF Gram stain was
      negative, but the elevated CSF lactic acid levels with encephalitis and red blood
      cells in the CSF indicated L. monocytogenes as the most likely pathogen. We
      present a case of L. monocytogenes encephalitis mimicking HSV-1 encephalitis.
      While receiving ampicillin therapy, the patient remained unresponsive for more
      than 1 week and then suddenly regained consciousness and recovered without
      neurologic sequelae.

PMID- 17509431
TI  - Modern drainage techniques for pain reduction during chest tube removal.

PMID- 17509432
TI  - What is the Association of Chiropractic Colleges Educational Conference and
      Research Agenda Conference?
AB  - This editorial presents a brief summary of the Association of Chiropractic
      Colleges Educational Conference and Research Agenda Conference (ACC-RAC) 2007,
      what it is and is not, and why one might wish to attend future ACC-RAC
      conferences.

PMID- 17509433
TI  - Interrater reliability and diagnostic accuracy of pelvic girdle pain
      classification.
AB  - OBJECTIVE: The purpose of this study was to measure the reliability of a
      classification system for pelvic girdle pain (PGP) and diagnostic accuracy of
      selected examination and clinical special findings for diagnosis of PGP. METHODS:
      The design involved a prospective epidemiological study of pregnancy-related PGP.
      Consecutive subjects were recruited and classified using criteria defined by
      previous studies. Two clinicians examined the subjects and classified each
      patient into 1 of 5 classification groups. Clinical examination and clinical
      special tests were performed on the patients with PGP. Statistical analysis
      involved interobserver agreement using a kappa statistic and sensitivity and
      specificity values for the examination and clinical special testing. RESULTS:
      Twenty-one subjects were included in the analyses. Aggregated percentage of
      agreement for the classification system was 84.6%. The Cohen kappa was 0.78 (CI,
      0.64-0.92; P < .0001), which indicated substantial agreement during selection of
      the classification system. Most clinical examination and clinical special-test
      findings demonstrated low sensitivity and high specificity, whereas clusters of
      findings including the lunge, manual muscle testing of the hip (lower
      extremities), and passive range of motion of the hip demonstrated the strongest
      diagnostic value. CONCLUSION: Selected tests and measures are moderately
      discriminatory in diagnosing PGP. A classification system for diagnosing PGP
      demonstrates strong agreement and may be useful for clinicians.

PMID- 17509434
TI  - Comparison of the Neck Disability Index and the Neck Bournemouth Questionnaire in
      a sample of patients with chronic uncomplicated neck pain.
AB  - OBJECTIVE: This study compares the sensitivity to change of the Neck Disability
      Index (NDI) and the Neck Bournemouth Questionnaire (NBQ) in patients with chronic
      uncomplicated neck pain. METHODS: This prospective longitudinal study was
      completed in an outpatient physical therapy clinic. Subjects, with uncomplicated
      neck pain (no concurrent shoulder pain or nerve root symptoms) for more than a 3
      month duration, participated in a 4-week course of therapy that included moist
      heat, neck exercises, and either mobilization or massage. Outcome measures
      included standardized response means (sensitivity to change), Cronbach alpha
      (internal consistency), and 2-way Spearman correlations between the 2
      questionnaires and between a pain Visual Analog Scale and each questionnaire
      (convergent validity). RESULTS: Mean (SD) score change of the NDI was 6.22
      (5.12), and of the NBQ, 14.00 (11.99). Standardized response means were 1.21 and
      1.17, respectively. Both questionnaires were more sensitive to change than the
      pain Visual Analog Scale (0.68). There was moderate correlation between the
      change scores of all 3 outcome tools (Spearman 0.46-0.57). The NBQ had higher
      internal consistency than the NDI. CONCLUSIONS: The NDI and the NBQ performed
      comparably in this group of patients with chronic uncomplicated neck pain. Both
      are sensitive to change and would be efficient outcome tools in studies of
      chronic neck pain. Both had acceptable internal consistency and are appropriate
      for use as single-outcome scales.

PMID- 17509435
TI  - Clinical utilization and cost outcomes from an integrative medicine independent
      physician association: an additional 3-year update.
AB  - OBJECTIVE: Our initial report analyzed clinical and cost utilization data from
      the years 1999 to 2002 for an integrative medicine independent physician
      association (IPA) whose primary care physicians (PCPs) were exclusively doctors
      of chiropractic. This report updates the subsequent utilization data from the IPA
      for the years 2003 to 2005 and includes first-time comparisons in data points
      among PCPs of different licensures who were oriented toward complementary and
      alternative medicine (CAM). METHODS: Independent physician association-incurred
      claims and stratified random patient surveys were descriptively analyzed for
      clinical utilization, cost offsets, and member satisfaction compared with
      conventional medical IPA normative values. Comparisons to our original
      publication's comparative blinded data, using nonrandom matched comparison
      groups, were descriptively analyzed for differences in age/sex demographics and
      disease profiles to examine sample bias. RESULTS: Clinical and cost utilization
      based on 70,274 member-months over a 7-year period demonstrated decreases of
      60.2% in-hospital admissions, 59.0% hospital days, 62.0% outpatient surgeries and
      procedures, and 85% pharmaceutical costs when compared with conventional medicine
      IPA performance for the same health maintenance organization product in the same
      geography and time frame. CONCLUSION: During the past 7 years, and with a larger
      population than originally reported, the CAM-oriented PCPs using a
      nonsurgical/nonpharmaceutical approach demonstrated reductions in both clinical
      and cost utilization when compared with PCPs using conventional medicine alone.
      Decreased utilization was uniformly achieved by all CAM-oriented PCPs, regardless
      of their licensure. The validity and generalizability of this observation are
      guarded given the lack of randomization, lack of statistical analysis possible,
      and potentially biased data in this population.

PMID- 17509436
TI  - Low back pain: clinimetric properties of the Trendelenburg test, active straight
      leg raise test, and breathing pattern during active straight leg raising.
AB  - OBJECTIVE: Classification of patients with low back pain (LBP) into subgroups is
      important as considerable variability exists in the LBP population. Clinical
      applicable, reliable, and valid tests to differentiate patients with LBP are
      therefore necessary. The purpose of this study is to examine the reliability,
      internal consistency, and clinical importance of 3 clinical tests that analyze
      motor control mechanisms of the lumbopelvic region in patients with nonspecific
      LBP. METHODS: Thirty-six patients with chronic nonspecific LBP volunteered for
      the study (cross-sectional design). The patients were examined by 2 assessors who
      were blinded to the results of each other. The following tests were performed:
      the Trendelenburg test, the active straight leg raise (ASLR) test, and the ASLR
      with visual inspection of the breathing pattern. RESULTS: The test-retest
      reliability coefficients (kappa) were greater than 0.75 for the Trendelenburg
      score and greater than 0.70 for the ASLR. The interobserver reliability
      coefficients were greater than 0.39 for the assessment of the breathing pattern
      during the ASLR. The Cronbach alpha coefficient for internal consistency of the
      Trendelenburg and ASLR tests was greater than .73. No significant associations
      were found between the outcome of the tests and self-reported pain severity or
      disability. CONCLUSIONS: These data provide evidence favoring the test-retest
      reliability of the Trendelenburg and ASLR tests in patients with LBP. The
      internal consistency of the outcome of these tests was high for both assessors,
      suggesting that these tests assess the same dimension. The interobserver
      reliability of the assessment of the breathing pattern was fair to moderate.
      Further research regarding the interobserver reliability, clinical importance,
      validity, and responsiveness of the Trendelenburg test, ASLR test, and breathing
      pattern during these tests is required.

PMID- 17509437
TI  - Introducing the external link model for studying spine fixation and misalignment:
      part 2, Biomechanical features.
AB  - OBJECTIVES: The purpose of this study was to characterize intervertebral
      stiffness and alignment changes in the external link model and evaluate it as an
      experimental mimic for studying the chiropractic subluxation. METHOD: A
      controlled test-retest design was used to evaluate rats with spine segments
      linked in 3 alignment configurations and controls that were never linked. Dorsal
      to-ventral spine stiffness was measured with a load platform, and
      flexion/extension misalignment was assessed on lateral radiographs obtained with
      a spine extension jig. Descriptive statistics were computed for study groups, and
      multiple linear regression models were used to examine all potential explanatory
      variables for the response variables "stiffness" and "joint position." RESULTS:
      Rats tested with links in place had significantly higher dorsal-to-ventral
      stiffness in the neutral configuration than rats in the flexed configuration.
      This difference remained after the links were removed. Stiffness after link
      removal was greater for longer linked periods. Surprisingly, stiffness after link
      removal was also greater with longer unlinked periods. Longer linked periods also
      produced greater misalignments during forced spine extension testing. Although
      link configuration was not a statistically significant predictor of
      misalignments, longer times after link removal did produce greater misalignments.
      CONCLUSIONS: This study suggests that the external link model can be a valuable
      tool for studying the effects of spine fixation and misalignment, 2 cardinal
      features of what has been historically described as the chiropractic subluxation.
      Significant residual stiffness and misalignment remained after the links were
      removed. The progressive course of this lesion is consistent with subluxation
      theory and clinical chiropractic experience.

PMID- 17509438
TI  - Process development for ethical recruitment of patients into simultaneous
      clinical studies in a chiropractic research clinic.
AB  - OBJECTIVE: To develop a process at one institution that creates an ethical means
      to bring other research projects to the attention of an individual who was
      excluded from the project for which they originally expressed interest, and to
      discuss the ethical issues surrounding patient recruitment and enrollment.
      METHOD: General consensus process via meetings of investigators involved in the
      ongoing trials at one institution. RESULTS: A process and flow sheet for offering
      new study information to individuals who did not meet the criteria for
      participation was developed. Once rejected, an individual can be asked if they
      wish to learn about other studies, are sent home with information, and are
      instructed to call back if they wish to volunteer. Consent can be used to take
      baseline information from the first study and apply it to the second. CONCLUSION:
      This process was developed and implemented for use in this research center.

PMID- 17509439
TI  - Unloaded movement facilitation exercise compared to no exercise or alternative
      therapy on outcomes for people with nonspecific chronic low back pain: a
      systematic review.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of unloaded
      movement facilitation exercises on outcomes for people with nonspecific chronic
      low back pain (NSCLBP). METHODS: This systematic review was conducted according
      to Cochrane Back Review Group and Quality of Reporting of Meta-analyses (QUORUM)
      guidelines. Exercise effects were reported as standardized mean difference (SMD)
      with 95% confidence intervals (95% CI). RESULTS: Six high-quality randomized
      controlled trials were included. For NSCLBP effects favored McKenzie therapy over
      intensive trunk strengthening for pain: SMD: short-term: 0.35 (0.10, 0.59); long
      term 0.36 (0.12, 0.61) and short-term function: SMD: 0.45 (0.20, 0.70) and were
      comparable for medium-term function: SMD: 0.15 (-0.90, 0.40). Effects of favored
      McKenzie therapy were comparable to specific spinal stabilization exercises for
      short-term pain: SMD: 0.63 (-0.11, 1.38) and function: SMD: 0.47 (-0.27, 1.20).
      Pooled effects favored McKenzie therapy over other exercises for short-term pain
      (pooled SMD: 0.38 (0.14, 0.61)) and were comparable for short-term function: SMD:
      0.10 (-0.20, 0.40). Yoga compared to trunk strengthening produced comparable
      effects for pain: (SMD: short-term: 0.13 (-0.46, 0.71); medium-term 0.51 (-0.08,
      1.11)) and function SMD: short-term: 0.51 (-0.08, 1.10); medium-term 0.38 (-0.22,
      0.97)). Compared to education, effects of yoga were large for medium-term pain
      and function (pooled SMDs: 0.92 (0.47, 1.37); 0.95 (0.50, 1.40)). Effects favored
      unloaded movement facilitation exercises of McKenzie compared to other or no
      exercise and were comparable for yoga. CONCLUSIONS: For NSCLBP, there is strong
      evidence that unloaded movement facilitation exercise, compared to no exercise,
      improves pain and function. Compared to other types of exercise, including effort
      intensive strengthening and time-intensive stabilization exercise, the effects
      are comparable. This challenges the role of strengthening for NSCLBP.

PMID- 17509440
TI  - Changes in neck pain and active range of motion after a single thoracic spine
      manipulation in subjects presenting with mechanical neck pain: a case series.
AB  - OBJECTIVE: Our aim was to report changes in neck pain at rest, active cervical
      range of motion, and neck pain at end-range of cervical motion after a single
      thoracic spine manipulation in a case series of patients with mechanical neck
      pain. METHODS: Seven patients with mechanical neck pain (2 men, 5 women), 20 to
      33 years old, were included. All patients received a single thoracic manipulation
      by an experienced manipulative therapist. The outcome measures of these cases
      series were neck pain at rest, as measured by a numerical pain rating scale;
      active cervical range of motion; and neck pain at the end of each neck motion
      (eg, flexion or extension). These outcomes were assessed pre treatment, 5 minutes
      post manipulation, and 48 hours after the intervention. A repeated-measures
      analysis was made with parametric tests. Within-group effect sizes were
      calculated using Cohen d coefficients. RESULTS: A significant (P < .001)
      decrease, with large within-group effect sizes (d > 1), in neck pain at rest were
      found after the thoracic spinal manipulation. A trend toward an increase in all
      cervical motions (flexion, extension, right or left lateral flexion, and right or
      left rotation) and a trend toward a decrease in neck pain at the end of each
      cervical motion were also found, although differences did not reach the
      significance (P > .05). Nevertheless, medium to large within-group effect sizes
      (0.5 < d < 1) were found between preintervention data and both postintervention
      assessments in both active range of motion and neck pain at the end of each neck
      motion. CONCLUSIONS: The present results demonstrated a clinically significant
      reduction in pain at rest in subjects with mechanical neck pain immediately and
      48 hours following a thoracic manipulation. Although increases in all tested
      ranges of motion were obtained, none of them reached statistical significance at
      either posttreatment point. The same was found for pain at the end of range of
      motion for all tested ranges, with the exception of pain at the end of forward
      flexion at 48 hours. More than one mechanism likely explains the effects of
      thoracic spinal manipulation. Future controlled studies comparing spinal
      manipulation vs spinal mobilization of the thoracic spine are required.

PMID- 17509441
TI  - Conservative treatment of a female collegiate volleyball player with
      costochondritis.
AB  - OBJECTIVE: This study was conducted to discuss the conservative care used to
      treat a female collegiate volleyball player with acute costochondritis. CLINICAL
      FEATURES: A 21-year-old collegiate volleyball player had right anterior chest
      pain and midthoracic stiffness of 8 months duration. INTERVENTION AND OUTCOME:
      High-velocity, low-amplitude manipulation was performed to the associated
      hypokinetic costovertebral, costotransverse, and intervertebral zygapophyseal
      thoracic joints. Instrument-assisted soft tissue mobilization was performed by
      using the Graston technique. Pain levels improved on numeric pain scale, as did
      functional status identified on Dallas Pain Questionnaire and Functional Rating
      Index. CONCLUSION: This athlete seemed to respond positively to manipulation,
      soft tissue mobilization, and taping.

PMID- 17509442
TI  - The ethics of educational research.

PMID- 17509443
TI  - Factors associated with patient satisfaction with chiropractic care: survey and
      review of the literature.

PMID- 17509444
TI  - Clarification on history of the AP open mouth radiograph.

PMID- 17509445
TI  - HLA-G expression is induced in Epstein-Barr virus-transformed B-cell lines by
      culture conditions.
AB  - Human leukocyte antigen-G (HLA-G) belongs to the nonclassical HLA class I family
      of genes presently designated as class Ib genes. It was found to be expressed
      mainly in placental tissue and in the thymus. Expression of HLA-G is induced by
      lymphokines such as interleukin-10 and has been associated with the escape of
      tumor cells from immune surveillance or with inhibition of graft rejection. In
      this report, Epstein-Barr virus-transformed B-cell lines established from
      peripheral blood lymphocytes from healthy volunteers were studied. Our results
      show that EBV-transformed B-cell lines, but not freshly separated peripheral
      blood lymphocytes, can be induced to express HLA-G either by subjecting the
      cultures to nutrient deficiency to hypoxia or to both, however, not all cell
      lines responded equally to stress conditions. The association of HLA-G with
      certain cancer transformations may suggest that the resistance to HLA-G
      expression could be related to susceptibility to the development of malignancy.

PMID- 17509446
TI  - Novel role for the N-terminus domain of the a2 isoform of vacuolar ATPase in
      interleukin-1beta production.
AB  - Interleukin-1beta (IL-1beta) is a mediator cytokine that is released by
      macrophages and epithelial cells in pregnancy and tumorigenesis before antigen
      recognition. a2V-ATPase is a protein expressed during pregnancy and tumorigenesis
      and has a novel role in immune regulation. It is expressed as a 70 kDa molecule
      in intracellular vesicles. Upon cell stimulation it migrates to the surface
      followed by the cleavage of a 20 kDa portion (a2 N-terminus domain, a2NTD). This
      study aimed to determine whether a2NTD could induce IL-1beta production in immune
      cells. Peripheral blood mononuclear cells (PMBC) were stimulated with a2NTD and
      analyzed for cytokine gene expression by gene arrays. Supernatants were analyzed
      for IL-1beta by enzyme-linked immunosorbent assay, and cells were analyzed for
      intracellular expression of IL-1alpha, IL-1beta, and TNF-alpha by flow cytometry.
      When PBMC were cultured with a2NTD, there was a 2.5-fold increase in IL1A and
      IL1B gene expression and no induction of TNF gene expression. There was a 72-fold
      increase in IL-1beta in supernatants of PBMC cultured with a2NTD. Finally, there
      was a 204-fold increase in intracellular expression of IL-1beta in monocytes
      incubated with a2NTD. These results indicate a regulatory role for a2NTD in IL-1
      cytokine production and suggest a unique role for this molecule in inflammation.

PMID- 17509448
TI  - The impact of human leukocyte antigen matching on transplant complications and
      immunosuppression dosage.
AB  - Administrative claims data facilitate ascertainment of outcomes not collected by
      the transplant registry and provide the opportunity to examine prescribed doses
      of immunosuppressive medications. Here, we examine the impact of human leukocyte
      antigen (HLA) matching on traditional outcomes, rejection and survival, and use
      novel methods to examine immunosuppresion doses and complication rates. The
      central hypothesis tested in this analysis is that HLA-matched recipients receive
      lower doses of immunosuppression and have fewer posttransplant complications. We
      break from tradition by examining HLA matching in both living and deceased donor
      kidney transplants. As secondary aims, we compare the relative impact of class I
      and II mismatches and describe outcomes achieved with older donors. Medicare
      claims linked to the United States Renal Data System database for 23,443 kidney
      transplants were included in the study. A total of 15,793 transplants were DR
      mismatched (DRMM), 5,340 manifested no DR mismatches (NODRMM), and 2,310
      manifested no ABDR mismatches (NOABDRMM). Patients with NOABDRMM experienced
      lower adjusted risk of rejection (0.66, 95% confidence interval 0.59-0.74, P <
      0.001) and lower hazard of graft loss (0.69, 0.61-0.77, P < 0.001) and death
      (0.76, 0.63-0.92, P < 0.001) compared with those with DRMM. The hazard of cardiac
      and diabetic complications was similar between recipients of NOADRMM and DRMM
      transplants, but the hazard of diarrhea was significantly lower (0.82, 0.73-0.92,
      P < 0.001) in patients with NOABDRMM. The 6-month dose of mycophenolate mofetil
      was lower in patients with NOABDRMM. This study validates previous studies that
      indicated significantly lower risks of rejection, graft loss, and death among
      patients with 0 HLA-A,B,DR mismatches. Use of administrative claims revealed
      similar rates of cardiovascular complications. However, HLA-matched deceased
      donor recipients received lower dosages of mycophenolate mofetil and manifested a
      lower risk of developing posttransplant diarrhea.

PMID- 17509447
TI  - Expansion of CD4+CD25+ suppressive regulatory T cells from rhesus macaque
      peripheral blood by FN18/antihuman CD28-coated Dynal beads.
AB  - CD4(+)CD25(+) regulatory T cells (Tregs) play an important role in allograft and
      self-tolerance and thus have potential therapeutic application in
      transplantation, autoimmunity, and allergy. Although nonhuman primate (NHP)
      provide the most accepted preclinical models for translational studies in
      allograft tolerance and infectious diseases, CD4(+)CD25(+) Tregs have been rarely
      studied in NHP. The low frequencies of Tregs in peripheral blood will likely
      necessitate ex vivo expansion to enable Tregs adaptive immune therapy in NHP and
      humans. Tregs were isolated by magnetic and flow sorting and then stimulated
      weekly with antirhesus CD3 clone FN18 and antihuman CD28-coated Dynal beads plus
      100 U/ml rhIL-2. Under these conditions, the Tregs were expanded 300- to 2000
      fold in 4 weeks. Expanded CD4(+)CD25(+) Tregs expressed high to moderate levels
      of FOXP3 as well as CD95, CD62L, CD69, and CCR7 surface antigens. Expanded rhesus
      Tregs were anergic and suppressed the proliferation of autologous peripheral
      blood mononuclear cells (PBMC) in a dose-dependent fashion, and the suppression
      was partially reversed by anti-transforming growth factor (TGF)-beta1
      neutralizing antibody (Ab). These results demonstrate that rhesus macaque
      suppressive regulatory CD4(+)CD25(+)FOXP3(+) Tregs can be efficiently expanded in
      vitro under rhesus-specific stimulation, which enables preclinical testing of
      Treg therapy in the NHP model.

PMID- 17509449
TI  - Immunoglobulin isotype-specific characterization of anti-human leukocyte antigen
      antibodies eluted from explanted renal allografts.
AB  - To evaluate the immunoglobulin isotypes of anti-human leukocyte antigen (HLA)
      antibodies harbored in rejected renal allografts, we isolated proteins by acid
      elution accumulated in 94 rejected and explanted kidneys and characterized their
      antibody specificities by complement-dependent cytotoxicity, enzyme-linked
      immunosorbent assay, and flow cytometry (Luminex) techniques. In addition, we
      differentially analyzed non-complement-binding immunolglobulin (Ig) G2/4 and
      IgA1/2 antibodies in the eluates using two modified solid phase assays. We found
      non-complement-binding IgG2 and IgG4 antibodies in 16/58 (28%) of the IgGall
      positive eluates, 15 eluates with anti-HLA class I and 4 with anti-HLA class II
      specificities, respectively. Anti-HLA class I IgG2/4 antibodies directed against
      the donor were found in 7 eluates (54% of the IgG2/4-pos. eluates), whereas 2
      eluates (50%) had class II IgG2/4 antibodies directed against the donor. IgA1/2
      antibodies could be detected in 9 eluates (16%); 5 of them had anti-HLA class I
      and 5 anti-HLA class II antibodies. We could clearly exhibit that explanted
      kidney allografts harbor anti-HLA antibodies. Moreover, our study demonstrates
      that non-complement-binding anti-HLA antibodies accumulate in rejected renal
      allografts.

PMID- 17509450
TI  - Natural killer cell crossmatch: functional analysis of inhibitory killer
      immunoglobulin-like receptors and their HLA ligands.
AB  - Attempts to predict outcome of bone marrow transplantation based on killer
      immunoglobulin-like receptor (KIR) and HLA genotyping have yielded discordant
      results. To better understand the factors involved, we investigated natural
      killer (NK) cell function and correlated it with genetics and expression of
      inhibitory KIR and HLA ligands in 20 normal allogeneic pairs. KIR expression was
      analyzed by flow cytometry to estimate the percentage of NK cells that could be
      inhibited by the HLA ligands in each pair combination. NK cytotoxicity against
      ConA blasts demonstrated a positive correlation between the number of KIR/HLA
      matches and the predicted number of NK cells that could be inhibited. When 50% or
      more of the NK cells could be inhibited, cytotoxicity was lower (8%) than when
      25% or less of the NK cells expressed KIR with matched HLA (49%) (p < 0.0001).
      Our data suggest that the interaction between inhibitory KIR and HLA ligands can
      be correlated to some extent with NK cell function, but measurement of NK
      activity may provide the best information for analysis of clinical situations.

PMID- 17509451
TI  - Evaluation of immune regulation in transplant patients using the trans vivo
      delayed type hypersensitivity assay.
AB  - Allograft recipient IL-10 and/or transforming growth factor-beta (TGF-beta)
      dependent anti-inflammatory T-cell delayed type hypersensitivity (DTH) responses
      to donor derived antigens, or regulatory T-cell responses, have been demonstrated
      in rodents and transplant patients using a previously described trans vivo DTH
      assay. We used this assay to determine the incidence of recipient anti
      inflammatory T-cell responses to donor antigens in a large cohort (n = 420) of
      primary kidney and simultaneous kidney-pancreas transplant patients tested a mean
      of 4.8 years after transplantation. The results were compared with clinical
      outcomes and the presence of detectable circulating alloantibodies. We found an
      unexpectedly high incidence (21.9%) of this anti-inflammatory T-cell response to
      donor antigens in these recipients. There was a significant correlation between
      this T-cell phenotype and the presence of detectable circulating alloantibodies
      (p = 0.03). There was no correlation between this T-cell phenotype and the degree
      of HLA mismatch. In addition, the presence of an anti-inflammatory DTH response
      to donor antigens did not correlate with an improved clinical outcome at a median
      of nearly 5 years after transplantation. These findings suggest that detection of
      an anti-inflammatory T-cell response to donor antigens does not identify patients
      that have developed graft protective, regulatory T-cell responses.

PMID- 17509452
TI  - DC-SIGN and DC-SIGNR genetic diversity among different ethnic populations:
      potential implications for pathogen recognition and disease susceptibility.
AB  - Dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin
      (DC-SIGN) and DC-SIGNR are C-type lectins that serve both as cell adhesion and
      pathogen recognition receptors. Because of the essential role of the these
      molecules in the immune response, the implication of their alleles in human
      disease states, and the possible genetic variation at these loci among ethnically
      diverse populations, we undertook a study to analyze the full extent of DC-SIGN
      and DC-SIGNR polymorphisms in Caucasian Canadian and indigenous African
      populations. We report several novel nucleotide variants within regulatory 5'-
      and 3'-untranslated regions of the genes that could affect their transcription
      and translation. There were significant differences in the distribution of DC
      SIGN and DC-SIGNR alleles among African and non-African populations. Finally, our
      study clearly demonstrates that Africans show greater genetic diversity at these
      two closely-related immune loci than observed in other major population groups.
      The differences may reflect evolutionary pressures generated by environmental
      factors, such as prevalent pathogens in these geographically distinct regions.
      Further studies will be needed to determine the net impact of DC-SIGN and DC
      SIGNR genetic variants on the expression, translation, and function of the
      proteins and to understand how these functional polymorphisms may affect immune
      responses or immune escape.

PMID- 17509453
TI  - HLA-A, -B, -C, and -DRB1 allele frequencies in Cuban individuals with antecedents
      of dengue 2 disease: advantages of the Cuban population for HLA studies of dengue
      virus infection.
AB  - Dengue virus infection has emerged as one of the most important arthropod-borne
      diseases. In some dengue-infected individual, the disease progresses to its
      severe, life-threatening form, dengue hemorrhagic fever (DHF). Host genetic
      factors may be relevant and predispose some individuals to the severe dengue
      disease. The unique history of dengue outbreaks in Cuba is extremely advantageous
      for genetic studies of dengue disease resistance or susceptibility. Consequently,
      samples collected from 120 healthy individuals that developed dengue fever (DF)
      and DHF during the 1997 dengue 2 outbreak in the Santiago de Cuba municipality
      were HLA genotyped using polymerase chain reaction-sequence-specific primers.
      Polymorphism at the human leukocyte antigen (HLA) class I loci was significantly
      associated with DHF disease susceptibility, but polymorphism in the HLA-DRB1 was
      associated with protection. Amino acid peptides present in the poly-protein of
      the dengue 2 Jamaica strain, which are able to bind to the HLA class I and class
      II allotypes associated with susceptibility to or protection against the dengue
      clinical disease, respectively, were predicted using the BIMAS and SYFPEITHI
      predictive algorithms of peptide/MHC interaction.

PMID- 17509454
TI  - The IL6 -174G/C polymorphism and sudden infant death syndrome.
AB  - The interleukin-6 genotype (IL6 -174GG) has been proposed to be associated with
      sudden infant death syndrome (SIDS). The aim of this study was to investigate the
      -174G/C polymorphism in 175 Norwegian SIDS cases and 71 controls. There were no
      differences in genotype distribution between these two groups (p = 1.0). This
      confirms the findings in a combined SIDS group compared with European Caucasian
      controls, but not findings in smaller cohorts of SIDS cases from Australia and
      England. The discrepancy may result from bias introduced when investigating only
      a few SIDS cases, differences in diagnostic criteria when diagnosing the cause of
      death as SIDS, and differences in the distribution of the -174G/C polymorphism in
      different ethnic groups. Findings of an activated immune system in SIDS indicate
      that genes involved in the immune response are of importance. However, because
      there are several polymorphisms in the IL6 gene promoter that could potentially
      regulate the expression of the gene, more than one polymorphism should be
      investigated to assess the involvement of the IL-6 gene in SIDS.

PMID- 17509455
TI  - Polymorphisms of interferon-gamma, interleukin-10, and interleukin-12 genes in
      myasthenia gravis.
AB  - To assess the involvement of polymorphisms in genetic susceptibility to
      myasthenia gravis (MG), this study analyzed four polymorphisms of interferon
      (IFN)-gamma, interleukin (IL)-10, and IL-12 genes in 115 patients and 204 healthy
      controls (HC). IFNG +874T carriers were less frequent in MG, in patients with
      anti-acetylcholine receptor (AChR) (63%) and anti-titin (56.2%) antibodies
      compared with HC (p = 0.01 for all, OR: 0.5, 0.5, and 0.4, respectively). The
      presence of thymoma was also associated with lower frequency of IFNG +874T allele
      (p = 0.018, OR = 0.34). At IL10, -2763A allele was found to be slightly more
      frequent in MG and in patients with anti-AChR than in HC group (p = 0.05, OR =
      1.7, p = 0.036, OR = 1.83). However, these associations did not remain
      significant after correction for multiple comparisons. IL12B allele distribution
      was not different among groups. These data suggest that some cytokine gene
      polymorphisms may contribute to susceptibility to or antibody production in MG.
      These findings need to be replicated in further studies.

PMID- 17509456
TI  - Origin of Tibeto-Burman speakers: evidence from HLA allele distribution in Lisu
      and Nu inhabiting Yunnan of China.
AB  - The issue about the origin of the Tibeto-Burman speaking ethnic groups (TBs)
      mostly residing in the Hengduan and Himalayan region in southwest China has been
      disputed for several decades. Based primarily on historical literatures and
      archaeologic findings the "Di-Qiang origin" hypothesis was proposed, in which the
      Tibeto-Burman speakers were thought to be descendants of the ancient Di-Qiang
      groups (DQs) who originated in northwest China. However, other evidence also
      challenge this hypothesis. In the present study, we investigate the distribution
      of HLA class I and class II genes in Lisu and Nu, two Tibeto-Burman-speaking
      ethnic groups, using a high-resolution polymerase chain reaction-sequencing-based
      typing method. Lisu and Nu share similar allele and haplotype frequencies of HLA
      class I and class II genes. Phylogenetic trees and principal component analysis
      based on HLA allele frequencies clearly indicated that Lisu and Nu clustered
      together with high bootstrap value, suggesting their close genetic relationship.
      The complicated genetic background of TBs was also revealed. The dendrogram based
      on HLA class II allelic frequencies demonstrated that East Asians clustered
      together and that four Tibeto-Burman-speaking ethnic groups (Naxi, Lahu, Lisu,
      and Nu) formed a clade clustering with southern East Asians (SEA), whereas
      another Tibeto-Burman speaker, Yi, integrated into the cluster of northern East
      Asians (NEA). Principal component analysis based on HLA class II allelic
      frequencies supported that TBs could be classified into two groups with Naxi,
      Lahu, Lisu and Nu scattering among SEA, while Yi locating close to NEA. A clear
      boundary between NEA and SEA was also observed in the principal component plot
      based on HLA class I allele frequencies and Lisu and Nu clustered into the SEA.
      In conclusion, our results provide evidences that not only DQs but also southwest
      aborigines may be ancestors of the TBs.

PMID- 17509458
TI  - A fearful patient's journey for dental help.

PMID- 17509460
TI  - Phase I trial of pirfenidone in children with neurofibromatosis 1 and plexiform
      neurofibromas.
AB  - We aimed to define the dose of pirfenidone in children and adolescents with
      neurofibromatosis 1 and plexiform neurofibromas that is pharmacokinetically
      comparable to the active adult dose. Pirfenidone was administered orally on a
      continuous dosing schedule. The starting dose level was 250 mg/m2/dose. The
      second dose level (500 mg/m2/dose) corresponded to the adult dose that previously
      showed activity in sclerosing conditions. A dose was considered
      pharmacokinetically comparable if the drug exposure in children was <1 standard
      deviation below the drug exposure in adults treated with 800 mg three times a
      day. Pharmacokinetic sampling was performed for 24 hours after the first dose.
      Response to treatment was evaluated using automated volumetric magnetic resonance
      imaging analysis; quality of life was evaluated using the Impact of Pediatric
      Illness Scale. Sixteen patients were entered and evaluated for toxicity. Dose
      limiting toxicities were observed in 2 of 12 patients receiving 500 mg/m2 three
      times a day. The plasma pharmacokinetics of pirfenidone were highly variable, but
      not age dependent. The second dose level was the pharmacokinetically comparable
      dose and is being used in an ongoing phase II trial of pirfenidone for children
      with neurofibromatosis 1 and progressive plexiform neurofibroma.

PMID- 17509459
TI  - The neuropharmacology of the ketogenic diet.
AB  - The ketogenic diet is a valuable therapeutic approach for epilepsy, one in which
      most clinical experience has been with children. Although the mechanism by which
      the diet protects against seizures is unknown, there is evidence that it causes
      effects on intermediary metabolism that influence the dynamics of the major
      inhibitory and excitatory neurotransmitter systems in brain. The pattern of
      protection of the ketogenic diet in animal models of seizures is distinct from
      that of other anticonvulsants, suggesting that it has a unique mechanism of
      action. During consumption of the ketogenic diet, marked alterations in brain
      energy metabolism occur, with ketone bodies partly replacing glucose as fuel.
      Whether these metabolic changes contribute to acute seizure protection is
      unclear; however, the ketone body acetone has anticonvulsant activity and could
      play a role in the seizure protection afforded by the diet. In addition to acute
      seizure protection, the ketogenic diet provides protection against the
      development of spontaneous recurrent seizures in models of chronic epilepsy, and
      it has neuroprotective properties in diverse models of neurodegenerative disease.

PMID- 17509461
TI  - Evolution of neurologic features in Williams syndrome.
AB  - As a part of a large multidisciplinary clinical and research follow-up study, 47
      Williams syndrome patients underwent detailed neurologic testing. Because
      previous studies have documented the absence of major neurologic signs in
      Williams syndrome, the neurologic testing focused on soft signs. Previous
      findings of impairment of both gross and fine motor coordination were confirmed,
      and the presence of mild cerebellar and extrapyramidal signs was documented. In a
      4-year follow-up study, an age-related pattern was revealed: soft extrapyramidal
      signs became more evident from 8 years of age and increased in the 14+ age group.
      The results are discussed according to a hypothesis related to the dopaminergic
      system involvement in Williams syndrome: anomalous organization or accelerated
      ageing process.

PMID- 17509462
TI  - Effects of febrile and afebrile seizures on oxidant state in children.
AB  - No comparative studies have addressed the oxidant and antioxidant states of blood
      and cerebrospinal fluid. To reveal this differential state, the study was
      designed to identify the seizure type with the worse prognosis by determining
      erythrocyte arginase and erythrocyte catalase, plasma and cerebrospinal fluid
      malondialdehyde, and plasma and cerebrospinal fluid nitric oxide levels. Study
      groups were classified as febrile (group 1, n = 21), afebrile (group 2, n = 21),
      and control (group 3, n = 41, subdivided as 3a, febris positive, convulsion
      negative, and 3b, febris negative, convulsion negative). Levels of erythrocyte
      arginase, erythrocyte catalase, plasma malondialdehyde, cerebrospinal fluid
      malondialdehyde, plasma nitric oxide, and cerebrospinal fluid nitric oxide levels
      were determined for all groups. A difference was detected between the control and
      febrile seizure groups with respect to erythrocyte catalase and plasma and
      cerebrospinal fluid levels of nitric oxide (P < 0.05). Both febrile states and
      convulsions influence oxidative mechanism. Oxidative stress-generating potential
      differs for febrile and afebrile seizures. In afebrile seizures, greater levels
      of oxidative stress might affect prognosis adversely. This phenomenon can be
      interpreted in terms of fever as a protective factor against possible
      neurological damage during convulsive seizures.

PMID- 17509463
TI  - Neuropsychologic performance of children with epilepsy on the NEPSY.
AB  - Neuropsychologic test scores from a group of children with epilepsy were compared
      to the standardization sample of the NEPSY: A Developmental Neuropsychological
      Assessment, a relatively new neuropsychologic testing instrument. Nineteen
      children with a confirmed diagnosis of epilepsy (11 boys, 8 girls), aged 3-12
      years, participated. Attention/executive function, language, sensorimotor,
      visuospatial, and learning/memory domain scores were examined, as well as
      individual subtest scores. The mean scores on the attention/executive function,
      language, and sensorimotor domains were >1.5 standard deviations below the
      normative mean, and significantly lower than the mean visuospatial domain score
      (P < 0.05). The mean language domain score was also significantly lower than the
      learning/memory score (P < 0.05). Mean subdomain scores varied, with impairment
      on two tasks measuring rapid automatic processing and graphomotor precision,
      respectively. On the majority of subtests, 15% or more of the sample scored in
      the impaired range. Associations between patient age, seizure onset age, seizure
      frequency, and antiepileptic medication status were not associated with outcome,
      perhaps due in part to the small sample size. The strengths and weaknesses of the
      NEPSY as a measure of neuropsychologic functioning in children with epilepsy, and
      its utility in highlighting risks to academic achievement are discussed.

PMID- 17509464
TI  - Acute seizure-related hospitalizations in children with newly diagnosed epilepsy.
AB  - Hospitalizations due to breakthrough seizures were studied in children with newly
      diagnosed epilepsy to evaluate (1) risk factors associated with such admissions,
      in particular the withholding of medication and subtherapeutic dose of
      anticonvulsants, and (2) the impact of the unscheduled hospitalization on
      subsequent seizure outcome. We recruited patients aged less than 18 years with
      newly diagnosed epilepsy who presented to the pediatric department in Tuen Mun
      Hospital between January 2002 and December 2003. Patients with acute seizure
      related hospitalization within 1 year after diagnosis were included as cases (n =
      36); patients with no such hospitalization were included as controls (n = 86).
      Treatment effect was analyzed at the last follow-up visit before January 2005.
      Significant univariate association was observed between seizure-related
      hospitalization and age at seizure onset (OR = 0.91, 95% CI 0.84, 1), idiopathic
      epilepsy (OR = 0.35, 95% CI 0.15, 0.81), no antiepileptic drug (OR = 3.67, 95% CI
      1.51, 8.18), and subtherapeutic doses of antiepileptic drug (OR = 9.9, 95% CI
      2.2, 43.8). Independent risk factors of such hospitalizations were etiology of
      epilepsy, no antiepileptic drug, subtherapeutic dose of antiepileptic drug, and
      history of febrile convulsion. Sixty-four percent of the cohort was seizure-free.
      Acute seizure-related hospitalization was associated with less favorable outcome
      (OR = 3.79, 95% CI 1.48, 9.26).

PMID- 17509465
TI  - Brain-derived neurotrophic factor rescues neurons from bacterial meningitis.
AB  - Mortality and neurologic deficits still occurs frequently following bacterial
      meningitis in children, despite antibiotic treatment. We investigated the
      neuroprotective effects of brain-derived neurotrophic factor (BDNF) on brain
      neurons in bacterial meningitis. The rat model of bacterial meningitis and a
      normal rat model were developed. Either BDNF or albumin was injected into the
      cerebral ventricle 24 hours after and before inoculation for 7 days,
      respectively. Three of the rats treated with albumin died during the course of
      treatment, but none of those treated with BDNF. The neuronal population in both
      cerebral cortex and hippocampus of the rats treated with BDNF markedly increased,
      compared with the rats treated with albumin, but there was no significant
      difference between the rats treated with BDNF after and before inoculation, nor
      between the normal rats treated with BDNF and albumin. The present findings
      indicate that BDNF could protect a large number of neurons in cerebral cortex and
      hippocampus from inflammatory brain injury in bacterial meningitis. The
      administration of exogenous BDNF may be a new and effective way to decrease
      mortality and improve sequelae following bacterial meningitis.

PMID- 17509466
TI  - Transient hypermetabolism of the basal ganglia following perinatal hypoxia.
AB  - Positron emission tomography can be used to evaluate brain function following
      perinatal hypoxia. This case report demonstrates transient hypermetabolism in the
      basal ganglia detected by glucose metabolism positron emission tomography study
      in a newborn who suffered hypoxic-ischemic encephalopathy and developed dystonic
      cerebral palsy later. A scan repeated at 4 years of age showed severe
      hypometabolism in the lentiform nuclei and thalami. Transient hypermetabolism in
      the basal ganglia following perinatal hypoxia may be related to excitotoxic
      damage causing permanent neurological symptoms in the form of dystonic cerebral
      palsy. Thus, positron emission tomography can help predict this form of cerebral
      palsy in neonates.

PMID- 17509467
TI  - Familial benign neonatal sleep myoclonus.
AB  - Benign neonatal sleep myoclonus is a nonepileptic syndrome characterized by
      myoclonic jerks during sleep. It occurs in the first weeks of life and
      disappears, in most cases, within 3 months. There are no sequelae, and
      psychomotor and cognitive development are normal. The syndrome is usually
      sporadic; only a few familial cases have been reported in the literature. This
      case report describes three members of a single family with benign neonatal sleep
      myoclonus and discusses its differentiation from other types of myoclonus.

PMID- 17509468
TI  - Nonclassic neurologic features in cryopyrin-associated periodic syndromes.
AB  - Neurologic manifestations in early childhood occur in the cryopyrin-associated
      periodic syndromes, especially in the chronic infantile neurological, cutaneous,
      and articular syndrome (CINCA) and the Muckle-Wells syndrome. Cryopyrin
      associated periodic syndromes are commonly linked to mutations in the cold
      induced autoinflammatory syndrome gene CIAS1 (current symbol, NLRP3) on
      chromosome 1. We describe three children with atypical cryopyrin-associated
      periodic syndromes, neurologic symptoms, and a Q705K mutation. Cryopyrin
      associated periodic syndrome screening should be considered for children with
      neurologic and other periodic symptoms with elevated inflammatory markers. This
      syndrome is treatable with anakinra.

PMID- 17509469
TI  - Transient hypogammaglobulinemia after antiepileptic drug hypersensitivity.
AB  - The case is described of a 32-month-old male with transient but long-lasting
      severe hypogammaglobulinemia subsequent to multiple drug hypersensitivity. The
      patient had remarkably decreased immunoglobulin levels (IgG 136 mg/dL, IgA 11
      mg/dL, and IgM 10 mg/dL) 3 months after hypersensitivity to phenobarbital and
      phenytoin. Immunological study revealed reduction of B-cell count and decreased
      lymphocyte proliferation response to Staphylococcus aureus Cowan. IgM secretory
      response to pokeweed mitogen and S. aureus Cowan was almost preserved, whereas
      IgG secretory response was markedly decreased. The patient was treated with
      intravenous immunoglobulin, although recurrent infection was not observed before
      treatment. His immunoglobulin levels became normal more than 5 years after the
      onset of hypogammaglobulinemia.

PMID- 17509470
TI  - Lupus anticoagulant and thrombosis following Henoch-Schonlein purpura.
AB  - A male adolescent developed a sinovenous thrombosis 4 weeks following a Henoch
      Schonlein purpura episode. A hypercoagulation evaluation revealed a positive
      lupus anticoagulant. This suggests an association between Henoch-Schonlein
      purpura and antiphospholipid antibody syndrome and is the first report of
      sinovenous thrombosis after Henoch-Schonlein purpura that was likely due to
      elevated antiphospholipids. Children who develop Henoch-Schonlein purpura with
      neurologic features including headache should be evaluated for sinovenous
      thrombosis and a hypercoagulable state.

PMID- 17509471
TI  - A novel ABCD1 gene mutation in a Chinese-Taiwanese patient with
      adrenomyeloneuropathy.
AB  - The ABCD1 gene mutation (previously ALD) has been reported in China, but not
      previously in Taiwan. This case report describes one Taiwanese patient whose
      clinical manifestations were compatible with adrenomyeloneuropathy. Direct
      sequencing for the ABCD1 gene of this patient and his mother detected a novel
      missense mutation, K513Q, in exon 6, the first such detected in a Taiwanese
      patient. Previous studies have suggested exon 6 as a possible hot segment of
      ABCD1 gene mutations in Chinese populations; however, most of the mutations in
      exon 6 presented as childhood cerebral adrenoleukodystrophy. K513Q is also the
      first novel mutation located within exon 6 and presenting with adult-onset
      adrenomyeloneuropathy in Chinese-Taiwanese.

PMID- 17509472
TI  - Time to expand US funding for stem-cell research.

PMID- 17509473
TI  - The bad news: stroke incidence is stable.

PMID- 17509474
TI  - The entorhinal cortex: an anatomical mediator of genetic vulnerability to
      Alzheimer's disease?

PMID- 17509475
TI  - MCI treatment trials: failure or not?

PMID- 17509476
TI  - Transdermal therapy in Parkinson's disease.

PMID- 17509477
TI  - Epilepsy drugs: getting it right the first time.

PMID- 17509478
TI  - Magnesium for neuroprotection after traumatic brain injury.

PMID- 17509479
TI  - Alzheimer's researchers open the doors to data sharing.

PMID- 17509480
TI  - Profile. Howard Feldman: master of dementia.

PMID- 17509482
TI  - Neurologists are not immune.

PMID- 17509483
TI  - Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire,
      UK, between 1981 and 2006: a population-based study.
AB  - BACKGROUND: UK stroke mortality data suggest that the incidence of haemorrhagic
      stroke has fallen in the past 20 years, but these data do not include deaths of
      individuals aged 75 years or over. Trends in the older population might differ,
      since cause varies with age. Our aim was to investigate changes in the population
      based incidence of intracerebral haemorrhage according to age and likely
      aetiology. METHODS: We used data from the Oxford Community Stroke Project (OCSP;
      1981-86) and the Oxford Vascular Study (OXVASC; 2002-06) to investigate changes
      in the incidence of intracerebral haemorrhage with time, above and below age 75
      years, together with associated risk factors and premorbid medications.
      Incidences were standardised to the 2001 census population of England and Wales.
      FINDINGS: In the population aged under 75 years the incidence of intracerebral
      haemorrhage decreased substantially (rate ratio 0.53, 95% CI 0.29-0.95; p=0.03),
      but the number of cases of intracerebral haemorrhage at all ages were similar in
      OXVASC and OCSP (52 vs 55 cases) as the proportion of cases occurring at 75 years
      and over tended to increase (2.0, 0.8-4.6; p=0.09). The incidence of
      intracerebral haemorrhage associated with premorbid hypertension (blood pressure
      >or=160/100 mm Hg) fell overall (0.37, 0.20-0.69; p=0.002), but the incidence of
      intracerebral haemorrhage associated with antithrombotic use was increased (7.4,
      1.7-32; p=0.007). Above age 75 years the proportion of cases who were non
      hypertensive with lobar bleeds and presumed to have had mainly amyloid-related
      haemorrhages, also increased (4.0, 1.1-17; p=0.003). INTERPRETATION: There has
      been a substantial fall in hypertension-associated intracerebral haemorrhage over
      the past 25 years, but not in the overall number of cases of intracerebral
      haemorrhage in older age-groups, in part due to a rise in intracerebral
      haemorrhage associated with antithrombotic use. These trends, along with the
      expected increase in prevalence of amyloid angiopathy with the ageing population,
      suggest that, in contrast to projections based on mortality data below age 75
      years, absolute number of cases of intracerebral haemorrhage might increase in
      future.

PMID- 17509484
TI  - Cortical morphology in children and adolescents with different apolipoprotein E
      gene polymorphisms: an observational study.
AB  - BACKGROUND: Alleles of the apolipoprotein E (APOE) gene modulate risk for
      Alzheimer's disease, with carriers of the epsilon4 allele being at increased risk
      and carriers of the epsilon2 allele possibly at decreased risk compared with non
      carriers. Our aim was to determine whether possession of an epsilon4 allele would
      confer children with a neural substrate that might render them at risk for
      Alzheimer's disease, and whether carriers of the epsilon2 allele might have a so
      called protective cortical morphology. METHODS: 239 healthy children and
      adolescents were genotyped and had repeated neuroanatomic MRI (total 530 scans).
      Mixed model regression was used to determine whether the developmental trajectory
      of the cortex differed by genotype. FINDINGS: Cortical thickness of the left
      entorhinal region was significantly thinner in epsilon4 carriers than it was in
      non-epsilon4 carriers (3.79 [SE 0.06] mm, range 1.54-5.24 vs 3.94 [0.03] mm, 2.37
      6.11; p=0.03). There was a significant stepwise increase in cortical thickness in
      the left entorhinal regions, with epsilon4 carriers having the thinnest cortex
      and epsilon2 carriers the thickest, with epsilon3 homozygotes occupying an
      intermediate position (left beta 0.11 [SE 0.05], p=0.02). Neuroanatomic effects
      seemed fixed and non-progressive, with no evidence of accelerated cortical loss
      in young healthy epsilon4 carriers. INTERPRETATION: Alleles of the apolipoprotein
      E gene have distinct neuroanatomic signatures, identifiable in childhood. The
      thinner entorhinal cortex in individuals with the epsilon4 allele might
      contribute to risk of Alzheimer's disease.

PMID- 17509485
TI  - Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild
      cognitive impairment: the InDDEx study.
AB  - OBJECTIVE: To assess the effect of rivastigmine in patients with mild cognitive
      impairment (MCI) on the time to clinical diagnosis of Alzheimer's disease (AD)
      and the rate of cognitive decline. METHODS: The study was a double-blind,
      randomised, placebo-controlled trial of up to 48 months. All patients had MCI
      operationally defined by having cognitive symptoms, a global clinical dementia
      rating stage of 0.5, a score of less than 9 on the New York University delayed
      paragraph recall test, and by not meeting the diagnostic criteria for AD. Primary
      efficacy variables were time to clinical diagnosis of AD, and change in
      performance on a cognitive test battery. This study is registered with the US
      National Institutes of Health clinical trials database (ClinicalTrials.gov),
      number NCT00000174. FINDINGS: Of 1018 study patients enrolled, 508 were randomly
      assigned to rivastigmine and 510 to placebo; 17.3% of patients on rivastigmine
      and 21.4% on placebo progressed to AD (hazard ratio 0.85 [95% CI 0.64-1.12];
      p=0.225). There was no significant difference between the rivastigmine and
      placebo groups on the standardised Z score for the cognitive test battery
      measured as mean change from baseline to endpoint (-0.10 [95% CI -0.63 to 0.44],
      p=0.726). Serious adverse events were reported by 141 (27.9%) rivastigmine
      treated patients and 155 (30.5%) patients on placebo; adverse events of all types
      were reported by 483 (95.6%) rivastigmine-treated patients and 472 (92.7%)
      placebo-treated patients. The predominant adverse events were cholinergic: the
      frequencies of nausea, vomiting, diarrhoea, and dizziness were two to four times
      higher in the rivastigmine group than in the placebo group. INTERPRETATION: There
      was no significant benefit of rivastigmine on the progression rate to AD or on
      cognitive function over 4 years. The overall rate of progression from MCI to AD
      in this randomised clinical trial was much lower than predicted. Rivastigmine
      treatment was not associated with any significant safety concerns.

PMID- 17509486
TI  - Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson's
      disease: a double-blind, double-dummy, randomised controlled trial.
AB  - BACKGROUND: Continuous dopaminergic drug delivery is an unmet medical need in
      advanced Parkinson's disease. The aim of this trial-Clinical Efficacy of
      Pramipexole And Transdermal Rotigotine in Advanced PD (CLEOPATRA-PD)-was to
      assess the efficacy of adjunct treatment with rotigotine in comparison with
      placebo and with pramipexole in levodopa-treated patients with advanced
      Parkinson's disease and wearing-off type motor fluctuations. METHODS: In this
      randomised controlled trial, eligible participants were randomly assigned to
      receive either rotigotine (up to 16 mg/24 h as a transdermal patch), pramipexole
      (up to 4.5 mg/day orally), or placebo for 6 months. Primary efficacy variables
      were absolute change in total hours "off" (assessed by home diaries) from
      baseline to end of study and responder rate (defined as the proportion of
      patients with >or=30% reduction in absolute off time per day). Analyses were done
      by intention to treat. This trial is registered with the US National Institutes
      of Health clinical trials database (ClinicalTrials.gov), number NCT00244387.
      FINDINGS: 204 patients were randomly assigned to receive rotigotine, 201 to
      receive pramipexole, and 101 to receive placebo; 427 (84%) completed the trial.
      The number of discontinuations in each group was similar; most were for adverse
      events. The mean dose of rotigotine was 12.95 mg/24 h (SD 3.54), the mean dose of
      pramipexole was 3.1 mg/day (1.24). Mean absolute change in off time from baseline
      was -2.5 h (SE 0.20) with rotigotine, -2.8 h (0.20) with pramipexole, and -0.9 h
      (0.29) with placebo. The absolute change in off time from baseline compared with
      placebo was -1.58 h (95% CI -2.27 to -0.90; p<0.0001) for rotigotine and -1.94 h
      (-2.63 to -1.25; p<0.0001) for pramipexole. Responder rates were 67% (134 of 200
      patients) for pramipexole, 59.7% (120 of 201 patients) for rotigotine, and 35%
      (35 of 100 patients) for placebo. INTERPRETATION: In terms of change in absolute
      off time, rotigotine was non-inferior to pramipexole. Continuous delivery of
      rotigotine as transdermal patches could offer similar efficacy to oral
      pramipexole in patients with fluctuating Parkinson's disease over 6 months of
      treatment.

PMID- 17509487
TI  - Migraine: a complex genetic disorder.
AB  - Although family and twin studies show that there is a genetic component to
      migraine, no genes predisposing to common forms of the disorder have been
      identified. The most encouraging findings have emerged from the identification of
      genes causing rare mendelian traits that phenotypically resemble migraine. These
      studies have pointed migraine research towards ion-transport genes; however,
      there is no direct evidence of the involvement of these genes in common forms of
      migraine. Family-based linkage studies have identified several chromosomal
      regions linked to common forms of migraine, but there is little consistency
      between studies. The modest success in the identification of contributing gene
      variants has stimulated research into more effective strategies. These include
      new phenotyping methods for genetic studies and new study designs-such as case
      control and whole-genome association studies-to identify common variants
      contributing to the trait.

PMID- 17509488
TI  - Epidemiology, aetiology, and clinical management of epilepsy in Asia: a
      systematic review.
AB  - Epilepsy is a significant, but often underappreciated, health problem in Asia.
      Here, we systematically review the literature on epidemiology, aetiology, and
      management of epilepsy in 23 Asian countries. Prevalence estimates are available
      for only 11 countries from door-to-door surveys and are generally low. Figures
      for annual incidence in China and India are similar to those in the USA and
      Europe but lower than those reported from Africa and Latin America. There is a
      peak in incidence and prevalence in childhood, but a second peak in elderly
      people, as seen in developed countries, has not been documented. The main causes
      are head injuries, cerebrovascular disease, CNS infections, and birth trauma.
      Availability of epilepsy care depends largely on economic factors. Imaging and
      neurophysiological facilities are available in most countries, but often only in
      urban centres. Costly drugs, a large treatment gap, limited epilepsy surgery, and
      negative public attitude to epilepsy are other notable features of management in
      Asia. An understanding of the psychosocial, cultural, economic, organisational,
      and political factors influencing epilepsy causation, management, and outcome
      should be of high priority for future investigations.

PMID- 17509489
TI  - Lyme neuroborreliosis: infection, immunity, and inflammation.
AB  - Lyme neuroborreliosis (LNB), the neurological manifestation of systemic infection
      with the complex spirochaete Borrelia burgdorferi, can pose a challenge for
      practising neurologists. This Review is a summary of clinical presentation,
      diagnosis, and therapy, as well as of recent advances in our understanding of
      LNB. Many new insights have been gained through work in experimental models of
      the disease. An appreciation of the genetic heterogeneity of the causative
      pathogen has helped clinicians in their understanding of the diverse
      presentations of LNB.

PMID- 17509490
TI  - Acute treatment and long-term management of stroke in developing countries.
AB  - Developing countries have some of the highest stroke mortality rates in the world
      that account for over two-thirds of stroke deaths worldwide. Hospital-based
      studies suggest that the patterns of stroke types and causes of stroke differ
      between developing and developed countries, resulting in differing needs for
      acute and long-term care. Data on stroke care provision in developing countries
      are sparse and most of the available studies are biased towards urban settings in
      reasonably resourced health-care systems. A general overview shows that the
      quality and quantity of stroke care is largely patchy in low-income and middle
      income countries, with areas of excellence intermixed with areas of severe need,
      depending upon patients' location, socioeconomic status, education, and cultural
      beliefs. Here we review the available literature on acute and long-term stroke
      management in developing countries. On the basis of available studies, largely
      from developed countries, we discuss the need to develop basic organised stroke
      unit care in developing countries.

PMID- 17509491
TI  - Brainstem signs with progressing atrophy of medulla oblongata and upper cervical
      spinal cord.

PMID- 17509493
TI  - Computed tomographic diagnosis of obturator hernia and its surgical management: a
      case series.
AB  - The obturator hernia is a rare type of hernia which usually presents in thin,
      elderly women. The preoperative diagnosis is typically difficult, with non
      specific signs and symptoms which result in a delay in the diagnosis. It can also
      be an incidental finding at exploratory laparotomy for a patient with intestinal
      obstruction. The treatment is surgical. A series of four females with obturator
      hernia is presented. All patients presented with a history of intestinal
      obstruction and the hernia was diagnosed preoperatively by computed tomography.
      All patients underwent a preperitoneal mesh repair with a favourable outcome. The
      diagnosis and the surgical approach are discussed.

PMID- 17509494
TI  - Nationwide questionnaire survey of the contemporary surgical management of
      pancreatic cancer in the United Kingdom & Ireland.
AB  - This paper reports the results of a questionnaire-based survey of pancreatic
      surgical specialists in the United Kingdom addressing aspects of staging,
      resection volume and outcome. A postal survey was undertaken of the 517 members
      of the Association of upper Gastrointestinal Surgeons of Great Britain and
      Ireland (AUGIS). 57 surgeons undertook pancreatic resection from 162 overall
      respondents. Cross-checking with the list of members of the Pancreatic Society of
      Great Britain and Ireland yielded 64 pancreatic surgeons. 734
      pancreaticoduodenectomy (PD) were reported by respondents compared with 822
      procedures according to Government maintained Hospital Episode Statistics. The
      modal resection volume performed per annum was 6-10. There were 24 in-hospital
      deaths in 732 resections (3%) mortality. For individual respondents the modal
      percentage mortality was 5% (0 to 16%). All clinicians with mortality rates in
      excess of 10% did less than 10 resections per annum. Respondents favoured
      "amylase rich discharge beyond 7th post-operative day" as optimal for definition
      of post-resection pancreatic fistula. Accepting the limitations of questionnaire
      surveys, the results provide an important overview of pancreatic surgical
      practice: pancreaticoduodenectomy is carried out by a range of specialists, lower
      volume resectionists appear to have poorer outcomes and this study shows
      widespread agreement on optimum terminology for post-operative pancreatic
      fistula.

PMID- 17509495
TI  - Transobturator tape as a day surgery procedure: a case control study.
AB  - This study aims to assess the suitability of the transobturator tape (TOT) as a
      day surgery procedure. A retrospective study of all the patients who underwent
      TOT as a day surgery procedure, at a tertiary referral centre in the south-west
      of Scotland, over a 3-year period (August 2002-July 2005). The outcome measures
      were as follows: complication rates (both intra- and immediate postoperative),
      voiding dysfunction rates, analgesic requirements and unscheduled in-patient ward
      admission following the procedure. One hundred and sixty-seven case notes were
      examined; the mean operating time was 14.7 min (range: 12-28 min, median: 14
      min). 97.8% of patients had blood loss <100 ml and the mean blood loss was 54 ml
      (range: 10-500 ml). None of the patients had major complications such as urethral
      or bladder injury or anaesthetic complications. 79.6% of patients had
      satisfactory postoperative voiding pattern achieved within the time frame of the
      DSU (08:30-17:00 hours). No patient had complete urinary retention. However, 34
      patients (20.4%) failed to achieve satisfactory voiding within that time frame
      and warranted in-patient admission. Three other patients required in-patient
      admission; the reasons being vaginal bleeding (n=1), postoperative nausea and
      vomiting (n=1) and postoperative pain (n=1). Therefore, a total of 37 patients
      required in-patient ward admission, with an admission rate of 22.2%. In
      conclusion, the transobturator tape procedure is suitable as a day surgery
      procedure in selected patients. There is minimal peri-operative morbidity, and
      nearly 80% of patients are discharged home within the scheduled time frame.

PMID- 17509496
TI  - A single stage liposuction and dermopexy for grade 3b and grade 4
      pseudogynecomastia after massive weight loss: an observational study.
AB  - Nineteen middle-aged males with grade 3b and grade 4 pseudogynecomastia following
      severe weight loss were treated by liposuction and simultaneous skin reduction.
      From 1997 through 2005 nine males with grade 3 and ten with grade 4
      pseudogynecomastia were included in this study. Ages ranged from 23 to 48 years.
      Author used two techniques for skin reduction: 1-the dermal mastopexy (keyhole
      design) for grade 4, and 2-the complete circum-areolar technique (concentric
      reduction) with de-epithelialization for grade 3b. The current technique offers a
      proper treatment for the pendulous female-like breast with inelastic and
      redundant skin. It obviates the need for secondary revision by providing a viable
      nipple-areola complex at the desired location and eliminating the dish-type
      deformity that may result from subcutaneous mastectomy. Patients were monitored
      for the following 18 to 39 months. While reviewing the literature other methods
      are compared and discussed but it is suggested that the method reported here has
      a number of advantages and is the treatment of choice in many such cases.

PMID- 17509497
TI  - Surgical management of stress urinary incontinence in Scotland and Wales: a
      questionnaire study.
AB  - Urodynamic stress incontinence is a common complaint. There have been over two
      hundred procedures described for treatment. In 2003, the Royal College of
      Obstetricians and Gynaecologists in London published a guideline highlighting the
      evidence for different surgical approaches. These guidelines are intended to
      guide practice in the United Kingdom, including the two countries that were
      surveyed. It was our impression however that more sub-urethral tape type
      procedures were taking place than was recommended. We therefore undertook a
      postal survey of the consultant gynaecologists in Scotland and Wales, to compare
      current practice with the evidence base, and also to assess practice from a
      clinical and manpower perspective. Two hundred and forty consultants were
      identified in Scotland (161) and Wales (79). About two-thirds of those who saw
      patients with stress incontinence would always arrange pre-operative
      physiotherapy, and the majority of consultants would always organise urodynamics
      preoperatively. There were several different choices of primary procedure, with
      Tension Free Vaginal Tape (TVT Gynecare- Johnson & Johnson) the most common
      option. More than half of the respondents in both countries would refer a patient
      with recurrent stress incontinence to a specialist. TVT was also the most common
      choice of procedure for recurrent stress incontinence. The procedures that have a
      grade A recommendation in the RCOG guideline are Burch colposuspension and TVT,
      and 72% in Scotland and 63% in Wales would perform one of these procedures as
      first choice. Clinical practice moves on and there are several new sub-urethral
      tape procedures available on the market. It is important to balance the available
      evidence base with new developments in order to optimise the management of this
      common condition.

PMID- 17509498
TI  - Diagnostic peritoneal aspiration--the foster child of DPL: a prospective
      observational study.
AB  - BACKGROUND: The abdomen is routinely considered as a possible source of bleeding
      in hypotensive and unevaluable blunt multitrauma patients. These patients are
      often unstable to be transported for abdominal computed tomography (CT). Emerging
      data on Focused Assessment with Sonography for Trauma (FAST) exam questions its
      initially reported high accuracy. We hypothesized that Diagnostic Peritoneal
      Aspiration (DPA), without a full lavage, accurately detects intraperitoneal blood
      if present in sufficient volume to cause hypotension and warrant emergent
      operation. METHODS: Over 24 months (July 2002-June 2004), 62 severe blunt trauma
      patients (Injury Severity Score: 32+/-17) with admission systolic blood pressure
      equal to or less than 90 mmHg were enrolled prospectively. Percutaneous DPA was
      performed after FAST. Aspiration of any quantity of blood was considered a
      positive test. Sensitivity and specificity of DPA and FAST were calculated
      against findings from abdominal CT, laparotomy, or autopsy. RESULTS: Twenty-two
      patients (35%) required emergent laparotomy and 39 (63%) died. DPA was performed
      in less than 1 min with no complications. Sensitivity and specificity of DPA was
      89% and 100%, respectively, whereas for FAST it was 50% and 95%. Two (3%) false
      negative DPA were recorded; one patient had a minor liver laceration with 250 ml
      of free blood and the other a leaking retroperitoneal pelvic hematoma in the
      presence of cirrhosis with 600 ml of bloody ascitic fluid. There were no false
      positive DPA. Nine (14.5%) false negative and two (3%) false positive FAST were
      recorded in patients who were found to have at laparotomy 1575+/-1070 ml of
      hemoperitoneum on average. CONCLUSIONS: Percutaneous DPA is accurate, rapid,
      safe, and superior to FAST for the diagnosis of abdominal blood as the source of
      hemodynamic instability, requiring emergent surgery, in blunt multitrauma
      patients.

PMID- 17509499
TI  - Endovascular repair of abdominal infrarenal penetrating aortic ulcers: a
      prospective observational study.
AB  - OBJECTIVE: Penetrating atherosclerotic ulcer generally occurs in elderly patients
      with systemic atherosclerosis, predominantly in the descending thoracic aorta,
      and it is uncommon in the infrarenal aorta. We reviewed our experience of
      endovascular treatment of penetrating aortic ulcer in the infrarenal aorta.
      METHODS: In the last 4 years, out of 348 patients who underwent abdominal aortic
      procedures, a total of 13 patients (12 men and 1 woman) were found to have an
      abdominal penetrating aortic ulcer, corresponding to an incidence of 3.7%. Mean
      age was 73+/-7 years. All patients had hypertension. Three lesions were
      discovered incidentally and 10 were symptomatic. All patients underwent
      endovascular treatment in the operating room. Follow-up included CT-A control at
      1, 4 and 12 months after the intervention, and yearly thereafter. RESULTS:
      Primary technical success was 100%. No postoperative death was observed. Mean
      operative time was 100+/-29 min. Mean blood loss was 168+/-133 ml. No patient
      required intensive care unit stay. We observed one major complication (transient
      ischemic attack). Mean hospital stay was 4+/-1 days. During a mean follow-up
      period of 26 months no endoleak, aneurysm evolution or stent graft failure was
      recognized in any patient. One patient died 24 months after the intervention
      after a stroke. CONCLUSIONS: In our experience, endovascular or repair of
      infrarenal aortic ulcer appears feasible, and midterm results satisfactory.

PMID- 17509500
TI  - Comparison of cardiac outputs during major surgery using the Deltex CardioQ
      oesophageal Doppler monitor and the Novametrix-Respironics NICO: a prospective
      observational study.
AB  - INTRODUCTION: Recent studies have emphasised the importance of optimisation of
      intraoperative fluid administration in patients undergoing major abdominal
      surgery. A variety of non-invasive devices capable of measuring cardiac output
      are available for this purpose. Most studies have used the Deltex CardioQ
      Oesophageal Doppler monitor (DCQ ODM, Deltex, Chichester, Sussex, UK). A
      relatively new, totally non-invasive cardiac monitor is now available, the
      Novametrix-Respironics NICO machine (Novametrix-Respironics, USA). AIMS: This
      pilot study compared cardiac output values obtained during major abdominal
      surgery from the simultaneous use of these two devices. OBJECTIVES: To assess the
      reproducibility and consistency of the readings obtained to determine whether
      these monitors can be used interchangeably for optimising perioperative fluid
      administration. METHODS: 182 simultaneous paired cardiac output readings were
      obtained from 12 consecutive patients undergoing prolonged major abdominal
      surgery. These were analysed using correlation coefficients, scattergrams and
      Bland Altman plots. RESULTS: Although the r value obtained for correlation was
      0.3639 (p<0.0001), the Bland Altman plot showed significant differences of
      between -4.1 and +5.1 lpm between the readings means with a bias of 0.5 lpm for
      the NICO over the DCQ ODM. In addition, a sequential plot of simultaneous cardiac
      outputs showed great disparity between the two devices in some patients.
      CONCLUSION: Caution should be exercised before using these monitors to optimise
      intraoperative fluid administration as potentially very large volumes of fluid
      may be administered to achieve surrogate endpoints. These devices need to be
      compared side by side with a gold standard method of determining cardiac output
      before they can be used interchangeably for optimising intraoperative fluid
      administration in abdominal surgery.

PMID- 17509501
TI  - Primary tumors of jejunum and ileum as a cause of intestinal obstruction: a case
      control study.
AB  - BACKGROUND: Small-bowel tumors are rare and account for 1-2% of all
      gastrointestinal neoplasms. Most of these tumors are found at surgery indicated
      for other diagnosis or intestinal obstruction. The rarity, unclear presentation
      and diagnostic difficulty of these tumors stimulated our interest to review our
      experience with emergency surgery for intestinal obstruction secondary to
      jejunoileal tumors. METHODS: We reviewed 17 patients operated on for intestinal
      obstruction secondary to benign and malignant primary tumors of jejunum and ileum
      at our institution the last 10 years. RESULTS: The series comprised 8 male and 9
      female patients, most of them younger than 49 years of age. The most frequent
      tumors found were GIST (36%) followed by lymphomas (24%) and adenocarcinomas
      (18%). Most tumors (65%) were located in the ileum. Mean survival for patients
      with malignant tumors was 19.5+/-13 months, and for patients with benign tumors
      72+/-20 months (p<0.05). CONCLUSION: Jejunoileal tumors present frequently in
      patients younger than 49 years of age. Ileal tumors are more likely to develop
      intestinal obstruction than jejunal tumors. Emergency surgery for these patients
      precludes a complete and negative margin resection and constitutes a risk factor
      for residual disease and short-term survival.

PMID- 17509502
TI  - Acute appendicitis in pregnancy--risk factors associated with principal outcomes:
      a case control study.
AB  - BACKGROUND: The aim of this study was to determine the risk factors associated
      with the principal outcomes in acute appendicitis during pregnancy: appendix
      perforation, and maternal and fetal mortality and maternal morbidity. METHODS:
      Fifty-two pregnant women who were diagnosed and operated upon acute appendicitis
      in Dicle University Hospital, Diyarbakir, Turkey were presented. RESULTS: The
      frequency of appendicitis was higher in second trimester. On laparotomy 21
      patients had perforated, 29 patients had non-perforated and 2 patients had normal
      appendix. Interval between symptom onset and operation was found as the only
      predictive variable, which was independently associated with the presence of
      appendiceal perforation. There was a significant difference between perforated
      and non-perforated patients about the rate of complications (52% vs. 17%).
      Gestational age (p=0.036), interval between symptom onset and operation (p=0.018)
      and white blood cell count (p=0.025) were the variables related with preterm
      labor. Tocolytic treatment after the onset of contractions could not prevent
      preterm labor. The rate of fetal mortality was 8%. CONCLUSIONS: Presence of
      perforation is the only predictive factor for maternal morbidity. The aim of the
      surgeon should be operating the patient before perforation. An observation period
      may be essential in equivocal patients, but should be individualized according to
      duration of symptoms and findings of physical examination. The interval between
      the symptom onset and operation should never exceed 20 hours. Tocolytics should
      be ordered for the patients with delayed presentation and advanced gestational
      age in order to prevent preterm labor and fetal loss.

PMID- 17509503
TI  - Are the outcomes of emergency Lichtenstein hernioplasty similar to the outcomes
      of elective Lichtenstein hernioplasty?
AB  - BACKGROUND: The safe use of polypropylene prosthesis for the repair of
      complicated inguinal hernias has been established even when small bowel resection
      was required. Few reports have completely addressed this subject; none have
      compared the outcomes of emergency and elective Lichtenstein hernioplasty.
      METHODS: From January 2001 to December 2003, 343 patients were electively
      operated for inguinal hernia and 62 for complicated inguinal hernia. A follow-up
      period of 17-57 months using the Quantitative and Qualitative Measurement
      Instrument for evaluation of Lichtenstein hernioplasty outcomes (QQMI) was
      completed for 48 emergency patients and 326 elective patients. RESULTS: The mean
      QQMI score showed that most patients felt that the outcomes of their surgery were
      very good or excellent. Mean QQMI score for elective surgery was 10.1 and 9.5 for
      emergency surgery. CONCLUSIONS: The outcomes of emergency Lichtenstein
      hernioplasty were inferior to the outcomes of elective Lichtenstein hernioplasty.

PMID- 17509504
TI  - Cervical cerclage: a review.
AB  - Cervical cerclage is a common prophylactic intervention that has been used in the
      management of second trimester loss for several decades, yet it remains one of
      the more controversial surgical interventions in obstetrics. The diagnosis of
      cervical insufficiency is notoriously difficult to make, and is usually a
      retrospective one based on a history of recurrent second trimester loss (or early
      preterm delivery) following painless cervical dilatation in the absence of
      contractions, bleeding, or other causes of recurrent pregnancy loss. This article
      reviews the current literature regarding the efficacy of transvaginal cerclage
      (in both an elective and emergency setting), therapeutic cerclage (whereby a
      suture is inserted on the basis of ultrasound evidence of cervical shortening)
      and transabdominal cerclage.

PMID- 17509505
TI  - Flame burns during laparoscopic cholecystectomy: a hidden danger of diathermy?

PMID- 17509506
TI  - Increased tissue stiffness during mammography may contribute to carcinogenesis.

PMID- 17509507
TI  - Tear evaporation rates in Sjogren syndrome and non-Sjogren dry eye patients.
AB  - PURPOSE: To reinvestigate tear evaporation rates in Sjogren syndrome (SS) and non
      Sjogren (non-SS) dry eye patients with a recently reported ventilated chamber
      evaporimeter system. DESIGN: Prospective case-control study. METHODS: A
      ventilated chamber evaporimeter system was used to measure tear evaporation
      rates. A DR-1 camera (Kowa, Nagoya, Japan) was used for tear lipid layer
      interference image acquisition. The Yokoi severity grading system was used for DR
      1 image evaluation. Twenty-four aqueous tear deficiency (ATD) eyes of 21
      consecutive patients with SS were studied (SS ATD group). Twenty-one ATD eyes of
      12 non-SS patients (non-SS ATD group) were examined as control subjects. RESULTS:
      Tear evaporation rates of the SS ATD group (5.9 +/- 3.5 [10(-7) g/cm(2) per
      second]) were significantly higher than those of the non-SS ATD group (2.9 +/-
      1.8 [10(-7) g/cm(2) per second]; P = .0009). The severity grading of DR-1 tear
      interference images of the SS ATD group was significantly higher (P = .03), along
      with significantly worse meibomian gland expressibility and vital staining
      scores, compared with those of the non-SS ATD group. CONCLUSIONS: Tear
      evaporation rates were higher in eyes of the SS ATD group compared with the non
      SS ATD group. Tear evaporation assessed in conjunction with tear lipid layer
      findings and meibomian gland expressibility provides an increased understanding
      in the differential diagnosis of dry eye states.

PMID- 17509508
TI  - Optical coherence tomography reader agreement in neovascular age-related macular
      degeneration.
AB  - PURPOSE: To determine the interreader and intrareader agreement at the Optical
      Coherence Tomography (OCT) Reading Center at Duke for images produced for an
      interventional neovascular age-related macular degeneration (AMD) clinical trial.
      DESIGN: Retrospective, observational case series. METHODS: OCT was performed
      using the Stratus OCT Fast Macular Thickness Map (Carl Zeiss Meditec, Dublin,
      California, USA) scan mode and a 7-mm line scan centered on the fovea.
      Experienced OCT readers, certified to grade scans according to a standardized
      protocol, independently determined whether a scan was gradable. If gradable, each
      of the scans was graded for multiple morphologic characteristics. In addition,
      retinal thickness, subretinal fluid thickness, and choroidal neovascularization
      (CNV) thickness at the fovea were measured for each gradable scan. Interreader
      agreement was determined among three reader pairs. Readers regraded a subset of
      scans and intrareader agreement was determined. RESULTS: The interreader
      agreement was high for scan gradability and scan grades among three reader pairs,
      ranging from 84% to 100% and from 84% to 96%, respectively. Similarly, the
      intrareader agreement for scan gradability and scan grade, including comparison
      of adjudicated scan grades with readjudicated scan grades, was high and ranged
      from 91% to 100% and from 79% to 98%, respectively, except for scan grades of
      retinal pigment epithelium atrophy, when CNV was present. Highly reproducible
      results also were found for quantitative thickness measurements. CONCLUSIONS:
      Well-trained OCT readers can grade independently, with a high level of
      interreader and intrareader agreement, multiple morphologic parameters of OCT
      scans obtained from eyes with neovascular AMD. Reproducible Stratus OCT scan data
      will be valuable to monitor treatment efficacy in interventional clinical trials
      of neovascular AMD.

PMID- 17509509
TI  - Clinical characteristics of exudative age-related macular degeneration in
      Japanese patients.
AB  - PURPOSE: To clarify the clinical characteristics of exudative age-related macular
      degeneration (AMD) in Japanese patients. DESIGN: Retrospective, observational,
      consecutive case series. METHODS: Two hundred and eighty-nine patients with
      neovascular AMD were examined. RESULTS: The authors classified the patients into
      three subtypes of neovascular AMD: polypoidal choroidal vasculopathy (PCV),
      retinal angiomatous proliferation (RAP), and typical AMD. One hundred and fifty
      eight patients (54.7%) were diagnosed with PCV and 102 patients (35.3%) with
      typical AMD. RAP was observed in 13 patients (4.5%). In 16 patients (5.5%), one
      eye had PCV and the other eye had typical AMD. Most patients with PCV and typical
      AMD had unilateral disease (81.6% and 94.1%, respectively) with a male
      preponderance (77.8% and 71.6%, respectively). Nine of 13 patients with RAP were
      female (69.2%). Patients with RAP were older (mean, 80.3 years for men and 75.3
      years for women) than patients with other subtypes. Serous and hemorrhagic
      pigment epithelial detachment developed in 69 patients (43.7%) with PCV, 22
      patients (21.6%) with typical AMD, and nine patients (69.2%) with RAP. In the
      patients with unilateral disease in each subtype, large drusen in the unaffected
      eye were seen in 24.0% with PCV, 30.2% with typical AMD, and 77.8% with RAP.
      CONCLUSIONS: Neovascular AMD in Japanese patients has different demographic
      features compared with that in White patients. In Japanese patients, there is a
      preponderance of PCV, male gender, unilaterality, and absence of drusen in the
      second eye, with the exception of RAP.

PMID- 17509510
TI  - The risk of retinal detachment in high myopia after small incision coaxial
      phacoemulsification.
AB  - PURPOSE: Report incidence and risk of retinal detachment (RD)after coaxial
      phacoemulsification in high myopic patients. DESIGN: Retrospective consecutive
      interventional study. METHODS:  SETTING: Vissum-Instituto Oftalmologico de
      Alicante, Spain. PATIENT OR STUDY POPULATION: A total of 439 eyes from 274 high
      myopic patients with spherical equivalent (SE) >or= 6.00 diopters (D) or axial
      length >or= 26.00 mm. Mean age 62.2, axial length 27.88 +/- 2.11 mm (26.0 mm to
      37.9 mm), SE -13.3 +/- 5.6 (-6.00 D to -46.0 D). MAIN OUTCOME MEASURES: Incidence
      of RD, vitreous loss, and neodymium yttrium aluminum garnet (Nd:YAG) capsulotomy
      were evaluated after surgery at one, three, six, and 12 months then annually with
      mean follow-up 61.5 +/- 29.6 months. RESULTS: Incidence of RD was 2.7% (12/439
      eyes). In eyes with <or= 50 years of age was 3.65% (three eyes) compared with
      eyes with > 50 years of age was 2.52% (nine eyes). Cumulative risk of RD
      development by Kaplan-Meier analysis in all patients was 0.47%, 0.71%, 1.71%,
      2.59%, and 3.28% at three, six, 15, 48, and 63 months until 105 months,
      respectively. In eyes <or= 50 years of age: the risk increases to 1.23% at three
      months and 4.46% at 63 months until 147 months, whereas eyes with > 50 years of
      age was 0.58% and 2.96% at six and 52 months until 118 months after cataract
      surgery, respectively. No significant correlation was found between the
      occurrence of RD and vitreous loss (P <or= .33) or Nd:YAG capsulotomy (P <or= .50
      Chi-square test). CONCLUSIONS: The incidence of RD in high myopic patients after
      coaxial phacoemulsification is 2.7%. A trend toward an increased incidence and
      risk in patients younger than 50 years of age was detected in this study.

PMID- 17509511
TI  - Alterations in endothelial cell density after photorefractive keratectomy with
      adjuvant mitomycin.
AB  - PURPOSE: To elucidate the distinct role of the intraoperative use of mitomycin C
      (MMC) on endothelial cell density after photorefractive keratectomy (PRK) in
      human eyes. DESIGN: Prospective, double-masked, randomized clinical trial.
      METHODS: One eye of 15 patients was treated with PRK with intraoperative use of
      topical 0.02% MMC (15 seconds), whereas the fellow eye was treated with Epipolis
      laser in situ keratomileusis (Epi-LASIK) in random order. Corneal confocal
      microscopy was performed in all eyes preoperatively and at one, three, six, and
      12 months after the surgery. Moreover, three endothelial images were acquired in
      each of 15 preoperative-normal eyes to evaluate the repeatability of measuring
      endothelial cell density. Repeated measures analysis of variance was used to
      compare the temporal variations of endothelial cell density between the two
      techniques and the changes of endothelial cell density over time. RESULTS: The
      coefficient of repeatability of endothelial cell count was 148 cells/mm(2).
      Preoperative endothelial cell density was not significantly different between the
      two groups (P = .82). Moreover, the effect of the treatment on the temporal
      variation of endothelial cell density was insignificant (P = .83), whereas the
      differences between the preoperative and the postoperative endothelial cell
      densities reached statistical significance (P <or= .05). Nonetheless, inclusion
      of the repeatability of the instrument on the analysis diminished these
      significant differences (P > .05). CONCLUSIONS: The prophylactic intraoperative
      application of MMC (up to 15 seconds) after PRK does not seem to affect the
      endothelial cell density.

PMID- 17509512
TI  - Functional macular mapping in patients with vitreomacular pathologic features
      before and after surgery.
AB  - PURPOSE: To evaluate the potential benefit of microperimetry and preferential
      hyperacuity perimeter (PHP) to document visual performance objectively in
      patients with macular hole and macular pucker undergoing macular surgery. DESIGN:
      Observational case series. METHODS: In 19 patients with macular hole and 18 with
      macular pucker, best-corrected visual acuity (BCVA; in logarithm of the minimum
      angle of resolution units), central retinal sensitivity, and presence and extent
      of metamorphopsia were documented before and four and 12 weeks after surgery.
      Macular sensitivity (mean sensitivity decibel [dB], stability of fixation) was
      determined using MP1 microperimetry (Nidek, Padova, Italy). The PreView-PHP (Carl
      Zeiss Meditec, Dublin, California, USA) was used to quantify metamorphopsia.
      RESULTS: Before surgery, mean BCVA was 0.68 +/- 0.25 (macular holes) and 0.58 +/-
      0.25 (macular pucker). Microperimetry demonstrated a mean retinal sensitivity of
      11.3 +/- 2.5 dB (macular holes) and 10.7 +/- 2.8 dB (macular pucker). Twelve
      weeks after surgery, mean BCVA improved to 0.53 +/- 0.26 (macular holes) and 0.33
      +/- 0.26 (macular pucker; P = .042 and P = .004). Accordingly, retinal
      sensitivity increased significantly with 12.8 +/- 1.9 dB (macular holes) and 12.7
      +/- 2.5 dB (macular pucker; P = .04 and P = .02) as well as stability of
      fixation. At 12 weeks, 47.3% of macular hole eyes and 66.7% of macular pucker
      eyes improved in BCVA, but a significantly higher number (68.4% [macular holes]
      and 77.8% [macular pucker]) demonstrated improvement in microperimetry results.
      PHP results showed no significant change of scotomas, patient reliability, or
      presence of metamorphopsia at any interval. CONCLUSIONS: A higher number of
      patients improved in microperimetry than in visual acuity testing. Therefore,
      microperimetry highlights the value of functional macular mapping for these
      patients and indicates that BCVA may underestimate functional benefit of surgery.

PMID- 17509513
TI  - Retinal breaks observed during pars plana vitrectomy.
AB  - PURPOSE: To quantitate the frequency and features of retinal breaks discovered at
      the time of vitrectomy and to evaluate the outcomes with prophylactic treatment.
      DESIGN: A consecutive, single-surgeon, retrospective, observational case series
      from a two-year period. METHODS: Medical records were reviewed for all patients
      who underwent primary, standard, three-port pars plana vitrectomy (PPV) between
      January 1, 2000, and December 31, 2001. Intraoperative findings recorded included
      the number, location, and categorization of retinal breaks and their method of
      management. Postoperative features recorded included the presence or absence of a
      retinal detachment (RD). RESULTS: There were 65 retinal breaks found in 48
      (11.6%) of 415 eyes and included 30 (7.2%) eyes with definite breaks, nine (2.2%)
      with suspicious breaks, and nine (2.2%) with probably preexisting breaks. Breaks
      that were described as being large (n = 5) were more commonly associated with the
      right-hand sclerotomy (P = .041), although other categories of breaks were not.
      After surgery, the overall incidence of RD was 2.2% (nine of 415 eyes). The rate
      of RD among the 48 eyes with retinal breaks (of any category) was also 2.1% (one
      eye). All RDs in this series occurred more than three months after initial
      vitrectomy and, accordingly, were probably unrelated to retinal breaks that
      occurred during surgery. CONCLUSIONS: Recognition of retinal breaks and
      intraoperative treatment with retinopexy and air-fluid exchange during vitrectomy
      reduces the postoperative risk of RD to that among eyes without observed
      intraoperative retinal breaks.

PMID- 17509514
TI  - Stem-loop probe with universal reporter for sensing unlabeled nucleic acids.
AB  - In this article, we present the design principles and application of a motif
      composed of a stem-loop probe (SP) hybridized to a fluorescently labeled
      universal reporter (UR) for sensing unlabeled nucleic acids. At room temperature,
      SP-UR is in the hairpin-closed form in which the fluorophore of UR is in
      proximity to the G bases of the hairpin, where consequently the fluorescent
      emission is quenched significantly. On hybridization with target, SP-UR is
      trapped in the hairpin-opened configuration in which the fluorophore and the G
      quenchers are apart. This turns off quenching, increases emission intensity, and
      signals the presence of target. Compared with the common approach that employs an
      oligonucleotide probe with a covalently linked fluorophore, the use of a
      fluorescently labeled universal reporter strand hybridized to an unlabeled stem
      loop probe provides a more efficient approach to the fabrication of nucleic acid
      sensors and microarrays potentially useful for real-time analysis.

PMID- 17509515
TI  - [How to do a laryngeal electromyography procedure?].

PMID- 17509516
TI  - [Indications and results of stereotactic radiosurgery with LINAC for the
      treatment of acoustic neuromas: preliminary results].
AB  - INTRODUCTION: Radiosurgery is presently becoming an alternative to microsurgical
      resection of acoustic neuromas. The interest of radiosurgery consists in its
      lower morbidity compared to surgery and likely in similar rates of long-term
      tumor control. The goal of our study was to assess the clinical outcome (hearing
      preservation and neurological complications) as well as tumor control after low
      dose radiosurgery for unilateral acoustic neuromas. MATERIAL AND METHODS: Since
      April 2002, 22 patients with untreated acoustic neuromas underwent stereotactic
      radiosurgery using a linear accelerator (LINAC) and a micromultileaf collimator
      (mMLC, Brain Lab) at a low-dose of 12 Gy. The average age was 56.4 years (range
      29-73 years). The treatment volume was 0.03 to 6.04 cm(3) (median 1.85 cm(3)).
      The median follow-up period was 18 months (range 6-36 months). RESULTS: No
      morbidity was observed during the treatment. Preservation of a serviceable
      hearing (classes I and II according to the Gardner-Robertson scale) was achieved
      in 10 of 14 patients (71%). Radiological tumor growth control was obtained in all
      patients (100%). Trigeminal neuropathy was observed in two patients. One of these
      patients also experienced a slight facial weakness. CONCLUSIONS: Low dose
      radiosurgery provides a low rate of post-therapeutic morbidity and yields the
      preservation of a serviceable hearing in 70% of cases. Tumor control is observed
      in all patients, but a longer follow-up period is needed to confirm the stability
      of the tumor size.

PMID- 17509517
TI  - [Peak Nasal Inspiratory Flow: learning curve for the measurement method and
      reproducibility].
AB  - OBJECTIVES: A prospective study on the learning curve and reproducibility of PNIF
      measurement with 18 different operators. MATERIAL AND METHODS: Five hundred
      twenty-eight patients in two groups were prospectively enrolled in this study
      from September 2003 to April 2004. The learning curve of the technique was
      monitored after five patients had been measured. Reproducibility was evaluated
      with all patients after two consecutive measurements. RESULTS: The technique was
      acquired by all operators after the fifth patient. The mean PNIF measurements in
      controls and patients were 86.02+/-36.96 l/min and 89.59+/-41.97 l/min,
      respectively. Reproducibility (PNIF2-PNIF1=5.51+/-24.93 l/min) was obtained for
      all operators, whatever the number of measurements taken. CONCLUSIONS: The study
      confirms the good reproducibility and the easy training in PNIF measurement.

PMID- 17509518
TI  - [Who am I: G...?].

PMID- 17509519
TI  - Stimulation of phosphoinositide 3-kinase/Akt signaling by copper and zinc ions:
      mechanisms and consequences.
AB  - The phosphoinositide 3'-kinase (PI3K)/Akt signaling cascade controls cellular
      processes such as apoptosis and proliferation. Moreover, it is a mediator of
      insulin effects on target cells and as such is a major regulator of fuel
      metabolism. The PI3K/Akt cascade was demonstrated to be activated by stressful
      stimuli, including heat shock and reactive oxygen species (ROS). This minireview
      focuses on activation of the pathway by exposure of cells to heavy metal ions,
      Cu2+ and Zn2+. It is hypothesized that stimulation of PI3K/Akt is the molecular
      mechanism underlying the known insulin-mimetic effects of copper and zinc ions.
      Following a brief summary of PI3K/Akt signaling and of activation of the cascade
      by Cu2+ and Zn2+, mechanisms of metal-induced PI3K/Akt activation are discussed
      with a focus on the role of ROS and of cellular thiols (glutathione, thioredoxin)
      and protein tyrosine phosphatases in Cu2+ and Zn2+ signaling. Finally,
      consequences of metal-induced PI3K/Akt activation are discussed, focusing on the
      modulation of FoxO-family transcription factors by Cu2+ and Zn2+.

PMID- 17509520
TI  - Regulation of glycogen concentration and glycogen synthase activity in skeletal
      muscle of insulin-resistant rats.
AB  - The aim of this study was to investigate the effect of insulin resistance on
      glycogen concentration and glycogen synthase activity in the red and white
      gastrocnemius muscles and to determine whether the inverse relationship existing
      between glycogen concentration and enzyme activity is maintained in insulin
      resistant state. These questions were addressed using 3 models that induce
      various degrees of insulin resistance: sucrose feeding, dexamethasone
      administration, and a combination of both treatments (dex+sucrose). Sucrose
      feeding raised triglyceride levels without affecting plasma glucose or insulin
      concentrations whereas dexamethasone and dex+sucrose provoked severe
      hyperinsulinemia, hyperglycemia and hypertriglyceridemia. Sucrose feeding did not
      alter muscle glycogen concentration but provoked a small reduction in the
      glycogen synthase activity ratio (-/+ glucose-6-phosphate) in red but not in
      white gastrocnemius. Dexamethasone administration augmented glycogen
      concentration and reduced glycogen synthase activity ratio in both muscle fiber
      types. In contrast, dex+sucrose animals showed decreased muscle glycogen
      concentration compared to dexamethasone group, leading to levels similar to those
      of control animals. This was associated with lower glycogen synthase activity
      compared to control animals leading to levels comparable to those of
      dexamethasone-treated animals. Thus, in dex+sucrose animals, the inverse
      relationship observed between glycogen levels and glycogen synthase activity was
      not maintained, suggesting that factors other than the glycogen concentration
      modulate the enzyme's activity. In conclusion, while insulin resistance was
      associated with a reduced glycogen synthase activity ratio, we found no
      correlation between muscle glycogen concentration and insulin resistance.
      Furthermore, our results suggest that sucrose treatment may modulate
      dexamethasone action in skeletal muscle.

PMID- 17509521
TI  - Assessing the molecular basis for rat-selective induction of the mitochondrial
      permeability transition by norbormide.
AB  - It was recently demonstrated that the rat-selective toxicant norbormide also
      induces rat-selective opening of the permeability transition pore (PTP) in
      isolated mitochondria. Norbormide is a mixture of endo and exo stereoisomers;
      however, only the endo forms are lethal to rats. In the present study we tested
      both endo and exo isomers as well as neutral and cationic derivatives of
      norbormide to: (i) verify if the PTP-regulatory activity by norbormide is
      stereospecific; (ii) define the structural features of norbormide responsible for
      PTP-activation, (iii) elucidate the basis for the drug species-specificity. Our
      results show that: (i) norbormide isomers affect PTP in a rat-selective fashion;
      however, no relevant differences between lethal and non-lethal forms are observed
      suggesting that drug regulation of PTP-activity and lethality in rats are
      unrelated phenomena; (ii) a (phenylvinyl)pyridine moiety represents the key
      element conferring the PTP-activating effect; (iii) cationic derivatives of rat
      active compounds accumulate in the matrix via the membrane potential and activate
      the PTP also in mouse and guinea pig mitochondria. These findings suggest that
      the norbormide-sensitive PTP-target is present in all species examined, and is
      presumably located on the matrix side. The species-selectivity may depend on the
      unique properties of a transport system allowing drug internalisation in rat
      mitochondria.

PMID- 17509523
TI  - Eating disorder pathology among overweight treatment-seeking youth: clinical
      correlates and cross-sectional risk modeling.
AB  - Preliminary research suggests that pediatric overweight is associated with
      increased eating disorder pathology, however, little is known about which
      overweight youth are most vulnerable to eating disorder pathology. We therefore
      investigated 122 overweight treatment-seeking youth to describe eating disorder
      pathology and mental health correlates, and to identify psychopathological
      constructs that may place overweight youth at increased risk for eating disorder
      pathology. Youth participated in a comprehensive assessment of eating disorders,
      mood and anxiety disorders, general psychopathology, and risk variables involving
      semi-structured clinical interviews and self- and parent-report questionnaires
      prior to the initiation of weight-loss treatment. Ten youth met criteria for an
      eating disorder, and over one-third endorsed recent binge eating. Eating disorder
      pathology was associated with depressive and anxious symptoms (p's<0.001).
      Structural equation modeling indicated increased negative affect, teasing
      experience, and thin-ideal internalization, and decreased perfectionism were
      associated with increased eating disorder pathology. Findings corroborate earlier
      work indicating that eating disorder pathology is elevated and clinically
      significant in overweight treatment-seeking youth, bolstering the need for mental
      health assessment of such individuals. Cross-sectional modeling proposed key
      variables that relate to eating disorder pathology in overweight treatment
      seeking youth, which following prospective replication, may inform the
      development of effective interventions for overweight and eating disorders.

PMID- 17509522
TI  - Lipid contribution to the affinity of antigen association with specific
      antibodies conjugated to liposomes.
AB  - Immunoliposomes, directed to clinically relevant cell-surface molecules with
      antibodies, antibody fragments or peptides, are used for site-specific diagnostic
      evaluation or delivery of therapeutic agents. We have developed intrinsically
      echogenic liposomes (ELIP) covalently linked to fibrin(ogen)-specific antibodies
      and Fab fragments for ultrasonic imaging of atherosclerotic plaques. In order to
      determine the effect of liposomal conjugation on the molecular dynamics of
      fibrinogen binding, we studied the thermodynamic characteristics of unconjugated
      and ELIP-conjugated antibody molecules. Utilizing radioimmunoassay and enzyme
      linked immunosorbent assay protocols, binding affinities were derived from data
      obtained at three temperatures. The thermodynamic functions DeltaH(o) , DeltaG(o)
      and DeltaS(o) were determined from van't Hoff plots and equations of state. The
      resultant functions indicated that both specific and nonspecific associations of
      antibody molecules with fibrinogen occurred through a variety of molecular
      interactions, including hydrophophic, ionic and hydrogen bonding mechanisms. ELIP
      conjugation of antibodies and Fab fragments introduced a characteristic change in
      both DeltaH(o) and DeltaS(o) of association, which corresponded to a variable
      contribution to binding by phospholipid gel-liquid crystal phase transitions.
      These observations suggest that a reciprocal energy transduction, affecting the
      strength of antibody-antigen binding, may be a singular characteristic of
      immunoliposomes, having utility for optimization and further development of the
      technology.

PMID- 17509524
TI  - Hypoxia activates the IGF-1 expression through STAT5b in human HepG2 cells.
AB  - Insulin-like growth factors (IGF), polypeptides that regulate growth,
      differentiation, and survival in cells and tissues, were found to enhance gene
      expression from both heterologous and homologous promoters in the presence of
      constitutively active STAT5. This highly conserved 700-bp DNA region contains two
      closely located consensus STAT5-binding sites. Hypoxia regulates the IGF-1 gene
      expression through the STAT5b. We confirmed STAT5b is up-regulated under hypoxic
      conditions, and the increased STAT5b binds strongly to the STAT5-binding sites 1
      and 2 contained within the distal 5'-flanking region of IGF-1 gene in HepG2
      cells. EMSA studies showed that STAT5-binding activities to the IGF-1 promoter
      distinctly increased under hypoxia in STAT5b-transfected COS-7 cells. The IGF-1
      gene expression was also increased by hypoxia in HepG2 cells. STAT5b expression
      was inhibited by siRNA experiments leading to decreased IGF-1. These results
      provide a basis of molecular targets for cancer treatment via the STAT5b-IGF-1
      pathway in solid tumor cells.

PMID- 17509525
TI  - Human Cementum Protein 1 induces expression of bone and cementum proteins by
      human gingival fibroblasts.
AB  - We recently presented evidence showing that a human cementoblastoma-derived
      protein, named Cementum Protein 1 (CEMP1) may play a role as a local regulator of
      cementoblast differentiation and cementum-matrix mineralization. This protein was
      shown to be expressed by cementoblasts and progenitor cells localized in the
      periodontal ligament. In this study we demonstrate that transfection of CEMP1
      into human gingival fibroblasts (HGF) induces mineralization and expression of
      bone and cementum-matrix proteins. The transfected HGF cells had higher alkaline
      phosphatase activity and proliferation rate and they expressed genes for alkaline
      phosphatase, bone sialoprotein, osteocalcin, osteopontin, the transcription
      factor Runx2/Cbfa1, and cementum attachment protein (CAP). They also produced
      biological-type hydroxyapatite. These findings indicate that the CEMP1 might
      participate in differentiation and mineralization of nonosteogenic cells, and
      that it might have a potential function in cementum and bone formation.

PMID- 17509526
TI  - Solution structure of the all L- and D-amino acid-substituted mucin 2 epitope
      peptides.
AB  - High-molecular-weight mucin 2 (MUC2) glycoproteins show an aberrant glycosylation
      pattern when expressed in human colon carcinoma: the oligosaccharide chains are
      shorter and some are missing. In our ongoing effort of MUC2 vaccine development,
      we have solved the NMR structure of the all L-amino acid and various D-amino acid
      substituted derivatives of the peptide TPTPTGTQTPT, previously identified as an
      epitope within the tandem repeat unit of the MUC2 glycoprotein. In the all L
      amino acid containing peptide and in peptide tpTPTGTQtpt (where lowercase letters
      mark the position of D-amino acids) we identified a type I beta-turn spanning
      through residues (3)TPTG(6) and (5)TGTQ(8), respectively. Our structural findings
      are in good agreement with the antibody recognition properties of the
      investigated peptides and demonstrate that peptides with good stability against
      enzymatic degradation can be designed with good antibody binding characteristics.

PMID- 17509527
TI  - In vitro formation of capillary networks using optical lithographic techniques.
AB  - Tissue engineering approaches have been developed for vascular grafts, but
      success has been limited to arterial replacements of large-caliber vessels. We
      have developed an innovative technique to transplant engineered capillary
      networks by printing techniques. Endothelial cells were cultured on a patterned
      substrate, in which network patterns were generated by prior optical lithography.
      Subsequently, the patterned cells were transferred to extracellular matrix and
      tissue at which point they changed their morphologies and formed tubular
      structures. Microinjection of dye showed that the micrometer-scale tubular
      structure had in vitro flow potential. When capillary-like networks engineered on
      amnion membranes were transplanted into mice, we found blood cells inside of the
      lumen of the transplanted capillary-like structure. This is the first report of
      the in vitro formation of capillary networks using cell transfer technique, and
      this novel technique may open the way for development of rapid and effective
      blood perfusion systems in regenerative medicine.

PMID- 17509528
TI  - Inhibition of the extracellular signal-regulated kinase signaling pathway is
      correlated with proteasome inhibitor suppression of coxsackievirus replication.
AB  - The ubiquitin/proteasome system (UPS), a major intracellular protein degradation
      pathway, plays a critical role in coxsackieviral replication. To elucidate the
      mechanisms by which the UPS regulates viral replication, we studied the influence
      of proteasome inhibition on signaling through the extracellular signal-regulated
      kinase (ERK) pathway, a pathway which has been previously demonstrated to be
      necessary for coxsackieviral replication and contribute to virus-mediated
      pathogenesis. We found that proteasome inhibition reduced coxsackievirus-induced
      ERK phosphorylation in a dose-dependent manner, which is correlated with an
      induction of the mitogen-activated protein kinase phosphatase-1 (MKP-1). Blockade
      of MKP induction by short-interfering RNA attenuated the loss of ERK
      phosphorylation, and subsequently restored viral replication. Our results suggest
      that inhibition of the ERK signaling pathway contributes, as least in part, to
      proteasome inhibitor-mediated reduction of coxsackievirus replication,
      demonstrating a converging function of major intracellular signaling and protein
      degradation pathways in the regulation of viral replication.

PMID- 17509529
TI  - Novel small molecule induces p53-dependent apoptosis in human colon cancer cells.
AB  - Using high-throughput screening with small-molecule libraries, we identified a
      compound, KCG165 [(2-(3-(2-(pyrrolidin-1-yl)ethoxy)-1,10b-dihydro
      [1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one)], which strongly activated p53
      mediated transcriptional activity. KCG165-induced phosphorylations of p53 at
      Ser(6), Ser(15), and Ser(20)(,) which are all key residues involved in the
      activation and stabilization of p53. Consistent with these findings, KCG165
      increased level of p53 protein and led to the accumulation of transcriptionally
      active p53 in the nucleus with the increased occupancy of p53 in the endogenous
      promoter region of its downstream target gene, p21(WAF1/CIP). Notably, KCG165
      induced p53-dependent apoptosis in cancer cells. Furthermore, we suggested
      topoisomerase II as the molecular target of KCG165. Together, these results
      indicate that KCG165 may have potential applications as an antitumor agent.

PMID- 17509530
TI  - The role of microRNA in the delayed negative feedback regulation of gene
      expression.
AB  - Oscillatory gene expression plays an important role in somite segmentation during
      the early developmental stages of vertebrates. Recent experimental studies have
      shown that microRNA can regulate gene expression by stimulating degradation of
      mRNA and/or repression of translation. In this communication, we incorporate
      miRNA into a previous mathematical model of gene expression with delayed negative
      feedback and demonstrate how this modified model can elucidate the possible
      effect of miRNA on the oscillatory gene expression. Our finding suggests that
      miRNA maybe a destabilizing or stabilizing factor in the dynamics of gene
      expression depending on the severity of its effect on mRNA degradation. Our
      finding provides testable hypothesis for experimental biologists to further
      investigate miRNA's increasing functional roles in regulating cellular processes
      and development.

PMID- 17509531
TI  - Dual enzymatic properties of the cytoplasmic peptide: N-glycanase in C. elegans.
AB  - The endoplasmic reticulum-associated degradation (ERAD) of misfolded
      (glyco)proteins ensures that only functional, correctly folded proteins exit from
      the ER and that misfolded ones are degraded by the ubiquitin-proteasome system.
      During the degradation of misfolded glycoproteins, some of them are subjected to
      deglycosylation by the cytoplasmic peptide:N-glycanase (PNGase). The cytosolic
      PNGase is widely distributed throughout eukaryotes. Here we show that the
      nematode Caenorhabditis elegans PNG-1, the cytoplasmic PNGase orthologue in this
      organism, exhibits dual enzyme functions, not only as PNGase but also as an
      oxidoreductase (thioredoxin). Using an in vitro assay as well as an in vivo assay
      system in budding yeast, the N-terminal thioredoxin domain and the central
      transglutaminase domain were found to be essential for oxidoreductase activity
      and PNGase activity, respectively. Occurrence of a C. elegans mutation affecting
      a catalytic residue in the PNGase domain strongly suggests the functional
      importance of this protein in higher eukaryotes.

PMID- 17509532
TI  - Discovery of novel inhibitors targeting enoyl-acyl carrier protein reductase in
      Plasmodium falciparum by structure-based virtual screening.
AB  - There is a dire need for novel therapeutics to treat the virulent malarial
      parasite, Plasmodium falciparum. Recently, the X-ray crystal structure of enoyl
      acyl carrier protein reductase (ENR) in complex with triclosan has been
      determined and provides an opportunity for the rational design of novel
      inhibitors targeting the active site of ENR. Here, we report the discovery of
      several compounds by virtual screening and their experimental validation as high
      potency PfENR inhibitors.

PMID- 17509533
TI  - The effect of quercetin phase II metabolism on its MRP1 and MRP2 inhibiting
      potential.
AB  - The present study characterises the effect of phase II metabolism, especially
      methylation and glucuronidation, of the model flavonoid quercetin on its capacity
      to inhibit human MRP1 and MRP2 activity in Sf9 inside-out vesicles. The results
      obtained reveal that 3'-O-methylation does not affect the MRP inhibitory
      potential of quercetin. However, 4'-O-methylation appeared to reduce the
      potential to inhibit both MRP1 and MRP2. In contrast, glucuronidation in general,
      and especially glucuronidation at the 7-hydroxylmoiety, resulting in 7-O
      glucuronosyl quercetin, significantly increased the potential of quercetin to
      inhibit MRP1 and MRP2 mediated calcein transport with inhibition of MRP1 being
      generally more effective than that of MRP2. Overall, the results of this study
      reveal that the major phase II metabolites of quercetin are equally potent or
      even better inhibitors of human MRP1 and MRP2 than quercetin itself. This finding
      indicates that phase II metabolism of quercetin could enhance the potential use
      of quercetin- or flavonoids in general-as an inhibitor to overcome MRP-mediated
      multidrug resistance.

PMID- 17509534
TI  - Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin
      extrusions/H(+)-organic cation antiporters.
AB  - The substrate specificities of human (h) multidrug and toxin extrusion (MATE) 1
      and hMATE2-K were examined to find functional differences between these two
      transporters by the transfection of the cDNA of hMATE1 and hMATE2-K into HEK293
      cells. Western blotting revealed specific signals for hMATE1 and hMATE2-K
      consistent with a size of 50 and 40kDa, respectively, in the transfectants as
      well as human renal brush-border membranes under reducing conditions. In the
      presence of oppositely directed H(+)-gradient, the transport activities of
      various compounds such as tetraethylammonium, 1-methyl-4-phenylpyridinium,
      cimetidine, metformin, creatinine, guanidine, procainamide, and topotecan were
      stimulated in hMATE1- and hMATE2-K-expressing cells. In addition to cationic
      compounds, anionic estrone sulfate, acyclovir, and ganciclovir were also
      recognized as substrates of these transporters. Kinetic analyses demonstrated the
      Michaelis-Menten constants for the hMATE1-mediated transport of
      tetraethylammonium, 1-methyl-4-phenylpyridinium, cimetidine, metformin,
      guanidine, procainamide, topotecan, estrone sulfate, acycrovir, and ganciclovir
      to be (in mM) 0.38, 0.10, 0.17, 0.78, 2.10, 1.23, 0.07, 0.47, 2.64, and 5.12,
      respectively. Those for hMATE2-K were 0.76, 0.11, 0.12, 1.98, 4.20, 1.58, 0.06,
      0.85, 4.32, and 4.28, respectively. Although their affinity for hMATE1 and hMATE2
      K was similar, the zwitterionic cephalexin and cephradine were revealed to be
      specific substrates of hMATE1, but not of hMATE2-K. Levofloxacin and
      ciprofloxacin were not transported, but were demonstrated to be potent inhibitors
      of these transporters. These results suggest that hMATE1 and hMATE2-K function
      together as a detoxication system, by mediating the tubular secretion of
      intracellular ionic compounds across the brush-border membranes of the kidney.

PMID- 17509535
TI  - CNR1 variation modulates risk for drug and alcohol dependence.
AB  - BACKGROUND: Human cannabinoid receptor 1 (CB1), which is encoded by the CNR1
      gene, may play a role in the development of substance dependence (SD). Following
      initial reports of association of CNR1 with SD, we studied multiple markers at
      this locus in a large case-control sample. METHODS: Ten CNR1 markers and 38
      ancestry-informative markers were genotyped in 451 healthy control subjects and
      550 SD (AD and/or DD) patients (including European Americans [EAs] and African
      Americans [AAs]). Common confounding effects on association analysis of
      population stratification and admixture, age, and sex were controlled for using
      regression analysis. Disease risk and protective alleles were fine-mapped using a
      linkage disequilibrium measure (delta). RESULTS: In EAs, risk for each SD subtype
      significantly increased with the number of "G" alleles at rs6454674 (single
      nucleotide polymorphisms [SNP]3). SNP3;G(+) (the genotypes containing a G allele)
      and SNP8;T/T genotypes had significant interaction effects (p = .0003 for
      comorbid DD and AD, .0002 for DD, and .007 for AD). SNP3 and SNP8 together
      exerted stronger genetic effects on SD than either did individually. The peak
      delta values among all the markers were seen for SNP3 and SNP8 (rs806368).
      CONCLUSIONS: We demonstrate that CNR1 variation and interactive effects play
      important roles in risk for both DD and AD.

PMID- 17509536
TI  - Increased prefrontal gyrification in a large high-risk cohort characterizes those
      who develop schizophrenia and reflects abnormal prefrontal development.
AB  - BACKGROUND: In our cohort considered at high risk (HR) of developing
      schizophrenia, we previously found a significant difference in extent of right
      prefrontal cortical folding between those who subsequently developed
      schizophrenia and a matched group who remained well. This study aimed to
      determine if this preexisting difference distinguished 17 individuals who
      developed schizophrenia from the 128 HR individuals in the cohort who remained
      well and to explore possible underlying differences in cortical composition.
      METHODS: Prefrontal cortical folding was measured by an automated version of the
      Gyrification Index (A-GI), a ratio reflecting extent of folding. Multivariate
      logistic regression assessed the probability that prefrontal A-GI predicts
      diagnostic outcome and subsequently assessed the effect on A-GI of regional
      cerebrospinal fluid and gray and white matter. RESULTS: High-risk individuals who
      subsequently developed schizophrenia were distinguished from the remaining cohort
      by increased right prefrontal cortex (PFC) A-GI. Mean right PFC gray matter
      volume also differed between groups, but white matter volume did not.
      Correlations of age with gray and white matter further distinguished groups and a
      linear regression analysis showed a significant interaction between age and
      diagnosis on mean volume of right PFC white matter. CONCLUSIONS: Increased A-GI
      appears to indicate abnormal right prefrontal development in those who develop
      schizophrenia.

PMID- 17509537
TI  - Configural cue performance in identical twins discordant for posttraumatic stress
      disorder: theoretical implications for the role of hippocampal function.
AB  - BACKGROUND: A significant subgroup of individuals with posttraumatic stress
      disorder (PTSD) exhibits chronic, unremitting symptomatology that has also been
      associated with smaller hippocampal volume. The hippocampus plays a significant
      role in configural processing of contextual cues that facilitates context
      appropriate extinction of conditioned fear. We test the hypothesis that
      hippocampus-based configural processing deficits are a pre-existing vulnerability
      factor for unremitting forms of PTSD. METHODS: Participants included male
      monozygotic twin pairs who were discordant for combat trauma. In 18 twin pairs
      the combat-exposed brother developed unremitting PTSD, whereas in 23 pairs the
      combat-exposed brother never developed PTSD. Participants were compared in the
      capacity to solve allocentric spatial processing tasks, and this performance was
      examined for its relationship to the severity of PTSD symptomatology and
      hippocampal volume. RESULTS: Although not completely differentiated from overall
      IQ, PTSD combat veterans demonstrated significantly impaired performance in
      configural processing relative to non-PTSD combat veterans. Despite having
      neither combat-exposure nor PTSD, the unexposed co-twins of combat veterans with
      PTSD displayed the same decrements as their brothers. Deficits were significantly
      related to PTSD severity and hippocampal volume. CONCLUSIONS: The current study
      provides the first evidence that the relevance of the hippocampus in PTSD might
      be related to pre-existing configural cue processing deficits that predispose
      individuals to develop unremitting forms of the disorder.

PMID- 17509538
TI  - Decreased serum levels of platelet-endothelial adhesion molecule (PECAM-1) in
      subjects with high-functioning autism: a negative correlation with head
      circumference at birth.
AB  - BACKGROUND: Accumulating evidence suggests that the immune system plays a role in
      the pathophysiology of autism, and that the adhesion molecules play an important
      role in the process of inflammation. This study was undertaken to determine
      whether serum levels of the adhesion molecules in subjects with high-functioning
      autism are altered as compared with those of normal controls. METHODS: Seventeen
      male subjects with high-functioning autism and 22 male age-matched unrelated
      healthy control subjects were enrolled. Serum levels of the soluble forms of
      platelet-endothelial adhesion molecule (PECAM-1), intracellular adhesion molecule
      (ICAM-1), and vascular cell adhesion molecule (VCAM-1) were measured. RESULTS:
      Levels of PECAM-1, but not ICAM-1, in the subjects with autism were significantly
      lower than those of control subjects. VCAM-1 showed a weak trend for a lowered
      level. There was a negative correlation between serum levels of PECAM-1 and head
      circumference at birth in the autistic subjects. CONCLUSIONS: These results
      suggest that PECAM-1 plays a role in the pathophysiology of high-functioning
      autism.

PMID- 17509539
TI  - Modification of dichotic listening (DL) performance by musico-linguistic
      abilities and age.
AB  - To increase our understanding of the phonemic processing skills of musical and
      non-musical subjects, the Dichotic Listening task was performed in children and
      adults with varying degrees of musical aptitude. The roles of maturation and
      musical training were also investigated. The results showed superior left ear
      monitoring skills among the adults who practised music regularly. This may
      indicate altered hemispheric functioning. Other musically talented subjects did
      not have the ability to control left ear functioning in an equal manner, for
      instance, the performance of musical children and their non-musical controls in
      the forced-left / left ear condition did not differ. Thus, regular music practice
      may have a modulatory effect on the brain's linguistic organization and
      therefore, the beneficial effects of music on other cognitive skills should not
      be underestimated.

PMID- 17509541
TI  - Strategic differences in algebraic problem solving: neuroanatomical correlates.
AB  - In this study, we built on previous neuroimaging studies of mathematical
      cognition and examined whether the same cognitive processes are engaged by two
      strategies used in algebraic problem solving. We focused on symbolic algebra,
      which uses alphanumeric equations to represent problems, and the model method,
      which uses pictorial representation. Eighteen adults, matched on academic
      proficiency and competency in the two methods, transformed algebraic word
      problems into equations or models, and validated presented solutions. Both
      strategies were associated with activation of areas linked to working memory and
      quantitative processing. These included the left frontal gyri, and bilateral
      activation of the intraparietal sulci. Contrasting the two strategies, the
      symbolic method activated the posterior superior parietal lobules and the
      precuneus. These findings suggest that the two strategies are effected using
      similar processes but impose different attentional demands.

PMID- 17509540
TI  - NMDA receptor-mediated extracellular adenosine accumulation is blocked by
      phosphatase 1/2A inhibitors.
AB  - We have previously demonstrated that NMDA receptor-mediated extracellular
      adenosine accumulation in neuronal cultures is receptor-mediated and requires
      calcium influx. Because protein kinase C (PKC) is a calcium-dependent enzyme, we
      hypothesized that activation of PKC might be involved in NMDA-mediated adenosine
      accumulation. PKC inhibitors, however, did not block NMDA-evoked adenosine
      accumulation, but rather, stimulated basal adenosine accumulation. These data
      suggested the possibility that NMDA receptor-mediated adenosine accumulation
      involves net dephosphorylation rather than phosphorylation of one or more
      substrates. Thus, inhibition of kinases would be expected to increase adenosine
      accumulation and inhibition of phosphatases would be expected to block adenosine
      accumulation. To test this hypothesis, we used the phosphatase 1/2A inhibitors
      calyculin A and okadaic acid. Both inhibitors significantly reduced NMDA-evoked
      adenosine accumulation. In contrast phosphatase 2B inhibitors did not block NMDA
      evoked adenosine accumulation. These data suggest that NMDA-evoked adenosine
      accumulation is mediated by activation of phosphatase 1/2A. We have established
      previously that NMDA-mediated adenosine accumulation is associated with adenosine
      kinase inhibition. However, adenosine kinase is not a direct substrate for
      phosphatase 1/2A because inhibition of phosphatase 1/2A did not abolish NMDA
      evoked adenosine kinase inhibition. Okadaic acid also had no effect on NO donor
      evoked adenosine accumulation, which previously has been shown to be associated
      with adenosine kinase inhibition. Dephosphorylation of one or more proteins other
      than adenosine kinase as a consequence of NMDA receptor activation might play an
      important role in extracellular adenosine regulation, with important consequences
      for the regulation of excitatory synaptic transmission, plasticity,
      epileptogenesis, and excitotoxicity.

PMID- 17509542
TI  - Dopamine receptor mRNA and protein expression in the mouse corpus striatum and
      cerebral cortex during pre- and postnatal development.
AB  - The outcome of dopaminergic signaling and effectiveness of dopaminergic drugs
      depend on the relative preponderance of each of the five dopamine receptors in a
      given brain region. The separate contribution of each receptor to overall
      dopaminergic tone is difficult to establish at a functional level due to lack of
      receptor subtype specific pharmacological agents. A surrogate for receptor
      function is receptor protein or mRNA expression. We examined dopamine receptor
      mRNA expression by quantitative reverse transcription real-time PCR in the
      striatum, globus pallidus, frontal cortex and cingulate cortex of embryonic and
      postnatal mice. Samples of each region were collected by laser capture
      microdissection. D1- and D2-receptor mRNAs were the most abundant in all the
      regions of the mature brain. The D1-receptor was predominant over the D2-receptor
      in the frontal and cingulate cortices whereas the situation was reversed in the
      striatum and globus pallidus. In the proliferative domains of the embryonic
      forebrain, D3-, D4- and D5-receptors were predominant. In the corpus striatum and
      cerebral cortex, the D3- and D4-receptors were the only receptors that showed
      marked developmental regulation. By analyzing D1 receptor protein expression, we
      show that developmental changes in mRNA expression reliably translate into
      changes in protein levels, at least for the D1-receptor.

PMID- 17509543
TI  - An improved methodology for the quantification of uronic acid units in xylans and
      other polysaccharides.
AB  - Uronic acids can be quantified either by a colorimetric determination after
      treatment with concentrated sulfuric acid and carbazole or by gas chromatography
      after methanolysis and subsequent acetylation. Both methods suffer from
      incomplete hydrolysis, an unavoidable degradation of the products to be analysed,
      and an inability to separate and quantify different types of uronic acids. In the
      present work, the fundamental chemistry involved in the two methods has been
      evaluated, and some modifications to increase their accuracy are suggested. By
      combining the two methods, a complete quantification of all individual types of
      uronic acids present in a sample can be achieved.

PMID- 17509544
TI  - Synthesis of (2R,5S)-dihydroxymethyl-(3R,4R)-dihydroxypyrrolidine (DGDP) via
      stereoselective amination using chlorosulfonyl isocyanate.
AB  - A stereoselective approach for synthesizing (2R,5S)-dihydroxymethyl-(3R,4R)
      dihydroxypyrrolidine 1 (2,5-dideoxy-2,5-imino-d-glucitol, DGDP) was achieved
      using a seven-step approach starting from 2,3,4,6-tetra-O-benzyl-d-mannose (7).
      Key steps for the preparation of the title compound 1 involved the regioselective
      and diastereoselective amination of the cinnamyl anti-1,2-polybenzyl ethers 5 and
      6 using chlorosulfonyl isocyanate (CSI) and ring cyclization to form the
      pyrrolidine ring. The reaction between anti-1,2-polybenzyl ether 5 and CSI in
      toluene at 0 degrees C afforded the corresponding anti-1,2-amino alcohol 4 as a
      major product with a diastereoselectivity of 16:1 in 76% yield. The mechanism
      underlying these reactions may be explained by the neighboring-group effect
      leading to the retention of stereochemistry.

PMID- 17509545
TI  - Crystal structure of a cyclomaltoheptaose-4-hydroxybiphenyl inclusion complex.
AB  - The crystal structure of the inclusion complex of cyclomaltoheptaose (beta
      cyclodextrin) with 4-hydroxybiphenyl was determined by single-crystal X-ray
      diffraction at 150K. The complex contains two cyclomaltoheptaose molecules, two 4
      hydroxybiphenyl molecules, one ethanol molecule and fifteen water molecules in
      the asymmetric unit, and could be formulated as
      [2(C(42)H(70)O(35)).2(C(12)H(10)O).(C(2)H(6)O).15(H(2)O)]. It crystallized in the
      triclinic space group P1 with unit cell constants a=15.257(3), b=15.564(3),
      c=15.592(2)A, alpha=104.485(15) degrees , beta=101.066(14) degrees ,
      gamma=104.330(17) degrees , V=3,343.6(10)A(3). In the crystal lattice, two beta
      cyclodextrins form a head-to-head dimer jointed through hydrogen bonds. Two 4
      hydroxybiphenyls were included in the dimer cavity with their hydroxyl groups
      protruding from two primary hydroxyl sides of the cyclodextrin molecules. The
      guest 4-hydroxybiphenyl molecules linked into a chain via a combination of an O
      Hcdots, three dots, centeredO hydrogen bond and face-to-face pi-pi stacking of
      the phenyl rings. The crystal structure supports the calculation results
      indicating that the 2:2 inclusion complex formed by beta-cyclodextrin and 4
      hydroxybiphenyl is the energetically favored structure.

PMID- 17509546
TI  - The O-specific polysaccharide structure from the lipopolysaccharide of the Gram
      negative bacterium Raoultella terrigena.
AB  - The structure of the repeating unit of the O-specific polysaccharide from the
      lipopolysaccharide of the enterobacterium Raoultella terrigena was determined by
      means of chemical and spectroscopical methods and was found to be a linear
      tetrasaccharide containing a cyclic acetal of pyruvic acid (Pyr) as depicted
      below.[Carbohydrate structure: see text].

PMID- 17509547
TI  - Study of hydration of cross-linked high amylose starch by solid state 13C NMR
      spectroscopy.
AB  - Starch is subjected to chemical treatments such as cross-linking or
      hydroxypropylation to meet the material requirements for food uses or controlled
      release in the pharmaceutical industries. In this work, two types of cross
      linking formulations have been employed for the preparation of high amylose
      starch for use as an excipient for sustained drug release. The structural
      differences and chain dynamics of the modified starches in the dry and hydrated
      states have been compared by the use of variable contact time cross polarization
      magic angle spinning solid state (13)C NMR spectroscopy.

PMID- 17509548
TI  - Synthesis of fused bicyclic thioglycosides of N-acylated glucosamine as analogues
      of mycothiol.
AB  - The synthesis of a fused bicyclic thioglycoside analogue of mycothiol, (3R)-3
      acetylamino-4-one-6,7-dihydro-(1',2'-dideoxy-beta-D-glucopyranoso)[2',1'-f]-1,5
      thiazepane (5), is reported. Treatment of phthalimido-protected peracetylated
      glucosamine with N-acetyl-cysteine and boron trifluoride-etherate gave the beta
      linked thioglycoside, which was deprotected and cyclized, using HOBt and EDCl to
      form the lactam and giving the target structure. This mycothiol mimic and its tri
      O-acetate will be investigated as potential inhibitors of enzymes involved in the
      biosynthesis of mycothiol. The protected derivative also has the potential to be
      an alpha-selective N-cysteinyl glucosamine donor; however, initial glycosylation
      attempts failed due to the apparent stability of the fused bicyclic system.

PMID- 17509549
TI  - Activation of alpha1B-adrenoceptors alleviates ischemia/reperfusion injury by
      limitation of mitochondrial Ca2+ overload in cardiomyocytes.
AB  - OBJECTIVE: Activation of alpha(1)-adrenergic receptors (alpha(1)-ARs) mimics
      ischemic preconditioning (IP). However, the subtypes of alpha(1)-ARs involved and
      the protective mechanisms are not entirely clear. Here we tested the hypothesis
      that preservation of mitochondrial integrity, in particular, Ca(2+) homeostasis
      via the epsilon isoform of protein kinase C (PKCepsilon) and mitoK(ATP) channels,
      may underlie the basis of alpha(1B)-AR-triggered cardioprotection. METHODS: Indo
      1 fluorescence in adult rat cardiomyocytes was used as an index of cytosolic
      ([Ca(2+)](c)) or mitochondrial free Ca(2+) concentration ([Ca(2+)](m)), and cell
      shortening was measured simultaneously. Cells were subjected to 20 min of
      simulated ischemia followed by 30 min of reperfusion (I/R). RESULTS: Activation
      of a(1)-ARs by phenylephrine significantly decreased I/R-induced [Ca(2+)](c) and
      [Ca(2+)](m) overload, mitochondrial cytochrome c release and ATP reduction, and
      improved Ca(2+) transients and cell shortening. These protective effects were
      markedly inhibited by blockade of alpha(1B)-AR (chloroethylclonidine) but not
      alpha(1A)-AR (5'-methylurapidil) or alpha(1D)-AR (BMY 7378). Moreover,
      phenylephrine-afforded protection on the [Ca(2+)](m), [Ca(2+)](c), and cell
      shortening was lost when mitoK(ATP) channels were inhibited with 5
      hydroxydecanoate and PKCepsilon with PKCepsilon V(1-2). However, PKCepsilon V(1
      2) did not affect the mitoK(ATP) channel opener diazoxide-induced protection on
      these parameters. CONCLUSIONS: These findings indicate that phenylephrine-induced
      protection on [Ca(2+)](m) homeostasis is mediated by selective activation of
      alpha(1B)-AR via mitoK(ATP) channel opening and PKCepsilon activation.
      Mitochondrial function appears to be a determinant of [Ca(2+)](c) and contractile
      function during I/R injury.

PMID- 17509550
TI  - Hypocholesterolemia and increased triglyceride in pediatric visceral
      leishmaniasis.

PMID- 17509551
TI  - A first familial G504S mutation of COL2A1 gene results in distinctive
      spondyloepiphyseal dysplasia congenita.

PMID- 17509552
TI  - Development of a novel microarray methodology for the study of SNPs in the
      promoter region of the TNF-alpha gene: their association with obstructive
      pulmonary disease in Greek patients.
AB  - OBJECTIVES: Polymorphisms in promoter region of TNF-alpha gene were shown to
      interfere with the transcriptional activity of the gene resulting in the
      production of different levels of TNF-alpha product suggesting their involvement
      in susceptibility or severity of many inflammatory diseases. We set up a case
      control study consisting of 117 COPD (Chronic Obstructive Pulmonary Disease), 62
      DB (bronchiectasis) patients and two control groups (109 smokers without COPD
      healthy smokers control group and 212 general population subjects) to evaluate
      involvement of TNF-alpha gene polymorphisms in the abovementioned diseases in a
      homogeneous population. METHODS: The novel methodology of the NanoChip Molecular
      Biology Workstation (MBW Nanogen http://www.nanogen.com) was employed to genotype
      the 5 promoter SNPs. RESULTS AND CONCLUSIONS: Genotype frequencies of the 5 SNPs
      showed no significant difference between the COPD and DB patient groups and the
      healthy smokers group. Statistical difference (p=0.043) was only revealed between
      the haplotype frequencies in COPD patients compared to the general population
      control group. The NanoChip MBW is an accurate method for SNP screening.

PMID- 17509553
TI  - Time in the mind: using space to think about time.
AB  - How do we construct abstract ideas like justice, mathematics, or time-travel? In
      this paper we investigate whether mental representations that result from
      physical experience underlie people's more abstract mental representations, using
      the domains of space and time as a testbed. People often talk about time using
      spatial language (e.g., a long vacation, a short concert). Do people also think
      about time using spatial representations, even when they are not using language?
      Results of six psychophysical experiments revealed that people are unable to
      ignore irrelevant spatial information when making judgments about duration, but
      not the converse. This pattern, which is predicted by the asymmetry between space
      and time in linguistic metaphors, was demonstrated here in tasks that do not
      involve any linguistic stimuli or responses. These findings provide evidence that
      the metaphorical relationship between space and time observed in language also
      exists in our more basic representations of distance and duration. Results
      suggest that our mental representations of things we can never see or touch may
      be built, in part, out of representations of physical experiences in perception
      and motor action.

PMID- 17509554
TI  - Mechanisms controlling Pax6 isoform expression in the retina have been conserved
      between teleosts and mammals.
AB  - The Pax6 gene plays several roles in retinal development, including control of
      cell proliferation, maintenance of the retinogenic potential of progenitor cells,
      and cell fate specification. Emerging evidence suggests that these different
      aspects of Pax6 gene function are mediated by different isoforms of the Pax6
      protein; however, relatively little is known about the spatiotemporal expression
      of Pax6 isoforms in the vertebrate retina. Using bacterial artificial chromosome
      (BAC) technology, we modified a zebrafish Pax6a BAC such that we could
      distinguish paired-containing Pax6a transcripts from paired-less Pax6a
      transcripts. In the zebrafish, the spatial and temporal onset of expression of
      these transcripts suggests that the paired-less isoform is involved in the cell
      fate decision leading to the generation of amacrine cells; however, because of
      limitations associated with transient transgenic analysis, it was not feasible to
      establish whether this promoter was active in all amacrine cells or in a specific
      population of amacrine cells. By making mice transgenic for the zebrafish Pax6a
      BAC reporter transgene, we were able to show that paired-containing and paired
      less Pax6a transcripts were differentially expressed in amacrine subpopulations.
      Our study also directly demonstrates the functional conservation of the
      regulatory mechanisms governing Pax6 transcription in teleosts and mammals.

PMID- 17509555
TI  - Neurturin-GFRalpha2 signaling controls liver bud migration along the ductus
      venosus in the chick embryo.
AB  - During chick liver development, the liver bud arises from the foregut,
      invaginates into the septum transversum, and elongates along and envelops the
      ductus venosus. However, the mechanism of liver bud migration is only poorly
      understood. Here, we demonstrate that a GDNF family ligand involved in neuronal
      outgrowth and migration, neurturin (NRTN), and its receptor, GFRalpha2, are
      essential for liver bud migration. In the chick embryo, we found that GFRalpha2
      was expressed in the liver bud and that NRTN was expressed in the endothelial
      cells of the ductus venosus. Inhibition of GFRalpha2 signaling suppressed liver
      bud elongation along the ductus venous without affecting cell proliferation and
      apoptosis. Moreover, ectopic expression of NRTN perturbed the directional
      migration along the ductus venosus, leading to splitting or ectopic branching of
      the liver. We showed that liver buds selectively migrated toward an NRTN-soaked
      bead in vitro. These data represent a new model for liver bud migration: NRTN
      secreted from endothelial cells functions as a chemoattractant to direct the
      migration of the GFRalpha2-expressing liver bud in early liver development.

PMID- 17509556
TI  - Human renal UOK130 tumor cells: a drug resistant cell line with highly selective
      over-expression of glutathione S-transferase-pi isozyme.
AB  - Drug resistance remains one of the primary causes of suboptimal outcomes in
      cancer chemotherapy. This study reports the development of a drug resistant cell
      line with over-expression of glutathione S-transferase (GST). The resistant tumor
      cell model was established by continuous exposure of UOK130, a human renal tumor
      cell line, to escalating concentrations of cisplatin. By immunoblotting the
      cisplatin-resistant cells (UOK(CR)) were found to express an elevated level of
      GST-pi isozyme. Neither alpha nor mu isozyme was detected by the corresponding
      polyclonal antibodies. A significant increase in cellular glutathione (GSH) was
      also observed in UOK(CR) cells comparative to the parental cells. In addition,
      the continuous exposure to cisplatin resulted in decreased cell susceptibility
      not only to cisplatin (resistant factor: 5.7) but also to melphalan (resistant
      factor: 2.9) and chlorambucil (resistant factor: 2.3). A transgenic cell line was
      developed by transfecting of UOK130 cells with GST-pi cDNA. The transfection of
      the GST-pi virus into UOK130 cell apparently increased its intracellular GST-pi
      activity. The resistance of the transfectants to cisplatin was consistently
      increased, compared with that of mock transfectants. A haloenol lactone (HEL)
      derivative known as a selective inhibitor of GST-pi was applied to evaluate the
      suitableness of the cell model for GST-pi-mediated drug resistance studies. The
      inhibitor was found to potentiate the cytoxicity of cisplatin to both UOK130 and
      UOK(CR) cell lines and to reverse their resistance to cisplatin. In conclusion,
      we developed a multiple drug resistant tumor cell line with selective over
      expression of GST-pi. The cell model provides a unique tool for mechanistic
      studies of drug resistance mediated by over-expression of GST-pi.

PMID- 17509557
TI  - Hyperbaric oxygen improves survival in heatstroke rats by reducing multiorgan
      dysfunction and brain oxidative stress.
AB  - Hyperbaric oxygen has been found to be beneficial in treating heatstroke animals.
      We attempted to further assess the possible mechanism of therapeutic protection
      offered by hyperbaric oxygen in experimental heatstroke. Anesthetized rats,
      immediately after the onset of heatstroke, were randomized into the following
      groups and given: a) hyperbaric oxygen (100% O(2) at 253 kPa for 1 h); or b)
      normal air. They were exposed to 43 degrees C temperature to induce heatstroke.
      When the untreated rats underwent heat stress, their survival time values were
      found to be 20-24 min. Resuscitation with hyperbaric oxygen increased the
      survival time to new values of 152-176 min. All untreated heatstroke rats
      displayed cerebrovascular dysfunction (evidenced by hypotension, intracranial
      hypertension, and cerebral hypoperfusion, hypoxia, and ischemia), hypercoagulable
      state (evidenced by increased levels of activated partial thromboplastin time,
      prothrombin time, and D-dimer, but decreased values of platelet count and protein
      C in plasma), and tissue ischemia/injury (evidenced by increased levels of
      creatinine, serum urea nitrogen, aspartate aminotransferase, alanine
      aminotransferase, and alkaline phosphatase in plasma, and dihydrobenzoic acid,
      lipid peroxidation, and oxidized-form glutathione/reduced-form of glutathione
      ratio in hypothalamus). The cerebrovascular dysfunctions, hypercoagulable state,
      tissue ischemia/injury, and brain oxidative stress that occurred during
      heatstroke were all suppressed by hyperbaric oxygen therapy. The current results
      indicate that hyperbaric oxygen therapy may resuscitate rats that had a
      heatstroke by decreasing multiple organ dysfunction and brain oxidative stress.

PMID- 17509558
TI  - Involvement of nitric oxide (NO) signaling pathway in the antidepressant action
      of bupropion, a dopamine reuptake inhibitor.
AB  - The present study was undertaken to elucidate the alterations in various
      behavioral and neurochemical basis of antidepressant action of bupropion [(+/-)
      alpha-t-butylamino-3-chloropropiophenone], a dopamine reuptake inhibitor and to
      elucidate the possible mechanism of its action. The involvement of L-arginine
      nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the
      antidepressant action of bupropion was investigated besides its actions on
      various brain transmitters like norepinephrine, dopamine and homovanillic acid.
      Bupropion (10, 15, 20 and 40 mg/kg., i.p.) dose dependently inhibited the
      immobility period in mice in both forced swim test and tail suspension test.
      ED(50) values of bupropion in reducing the immobility period was found to be 18.5
      and 18 mg/kg i.p., in forced swim test and tail suspension test, respectively.
      Bupropion (10, 20 and 40 mg/kg., i.p.) reversed the reserpine-induced behavioral
      despair also. When different doses (10, 15, 20 and 40 mg/kg., i.p.) of bupropion
      were tested for locomotor activity, it (15, 20 and 40 mg/kg., i.p.) increased
      locomotor activity. At 20 and 40 mg/kg doses the drug showed hypothermia. The
      neurochemical analysis of brain samples revealed that bupropion dose dependently
      (10-40 mg/kg., i.p.) increased the brain contents of dopamine and homovanillic
      acid in the mouse whole brain. The levels of norepinephrine were also increased
      at 20 mg/kg dose. The antidepressant-like effect of bupropion (20 mg/kg., i.p.)
      was prevented by pretreatment with L-arginine (750 mg/kg., i.p.) [substrate for
      nitric oxide synthase (NOS)]. Pretreatment of mice with 7-nitroindazole (25
      mg/kg., i.p.) [a specific neuronal nitric oxide synthase (nNOS) inhibitor]
      produced potentiation of the action of subeffective dose of bupropion (10 mg/kg
      i.p.). In addition, treatment of mice with methylene blue (10 mg/kg., i.p.)
      [direct inhibitor of both nitric oxide synthase (NOS) and soluble guanylate
      cyclase (sGC)] potentiated the effect of bupropion (10 mg/kg., i.p.) in the
      forced swim test. Furthermore, the reduction in the immobility period elicited by
      bupropion (20 mg/kg., i.p.) was also inhibited by pretreatment with sildenafil (5
      mg/kg., i.p.) [phosphodiesterase 5 inhibitor]. The study indicated that bupropion
      possesses antidepressant activities in different animal models of depression
      through its dopaminergic and/or by modulating the L-arginine-nitric oxide (NO)
      cyclic guanosine monophosphate (cGMP) signaling pathway.

PMID- 17509559
TI  - Modification of alterations in cardiac function and sarcoplasmic reticulum by
      astragaloside IV in myocardial injury in vivo.
AB  - Astragaloside IV, the primary pure saponin isolated from Astragalus membranaceus
      has been found to have potent cardioprotective effects. In this study, we aim to
      investigate if the beneficial effects of astragaloside IV on cardiac function are
      associated with improvement in sarcoplasmic reticulum Ca(2+)-pump function in
      myocardial injury in vivo. Myocardial injury in rats was induced by subcutaneous
      injection of a high dose of isoproterenol, and the therapeutic effect of
      astragaloside IV was observed. Isoproterenol-treated rats showed widespread
      subendocardial necrosis, a rise in serum lactate dehydrogenase and creatine
      kinase, formation of lipid oxide product malondialdehyde and inhibition of left
      ventricular diastolic and systolic function, which suggested severe myocardial
      injury and acute heart failure. Moreover, sarcoplasmic reticulum Ca(2+)-uptake
      ability and Ca(2+)-ATPase (SERCA2a) activity were significantly reduced. And the
      level of SERCA2a mRNA and protein expression was also markedly decreased,
      associated with a decrease in Ser(16)-phosphorylated phospholamban protein
      expression, while total phospholamban level was unchanged in the isoproterenol
      treated group compared with controls. However, these biochemical and hemodynamic
      changes in the acute failing hearts were prevented by treatment of isoproterenol
      induced rats with astragaloside IV. Likewise, the observed reductions in
      sarcoplasmic reticulum Ca(2+)-pump function as well as in SERCA2a mRNA and
      protein levels and the phosphorylation level of phospholamban in the injured
      hearts were attenuated by astragaloside IV treatment. These results suggest that
      the beneficial effect of astragaloside IV on isoproterenol-induced myocardial
      injury may be due to its ability to prevent changes of SERCA2a and Ser(16)
      phosphorylated phospholamban protein expression and, thus, may prevent the
      depression in sarcoplasmic reticulum Ca(2+) transport and improve cardiac
      function.

PMID- 17509560
TI  - Expression of purinergic P2Y receptor subtypes by INS-1 insulinoma beta-cells: a
      molecular and binding characterization.
AB  - Purinergic P2Y-receptor agonists amplify glucose-induced insulin secretion from
      pancreatic beta-cells, thus offering new opportunities for the treatment of type
      2 diabetes. However, little is known about which subtypes of purinergic P2Y
      receptors are expressed in these cells. The INS-1 beta-cell line is used as a
      model of pancreatic beta-cells, expressing most of their properties. Therefore,
      we investigated the expression of different molecular subtypes in this cell line
      by means of real time Polymerase Chain Reaction and Western blot. We also
      performed a characterization of the binding of a prototypic purinergic P2Y
      agonist, Adenosine-5'-O-(1-[(35)S]thiotriphosphate) (ATP-alpha-[(35)S]), to cell
      membrane homogenates. The molecular analysis evidenced the presence of five
      different purinergic P2Y receptor subtypes (P2Y(1), P2Y(2), P2Y(4), P2Y(6) and
      P2Y(12)), which were expressed at similar levels. The Western blot analysis
      allowed detecting corresponding proteins. The binding assay demonstrated a
      specific ATP-alpha-[(35)S] interaction on high (40%) and low (60%) affinity
      components. The analysis of ATP-alpha-[(35)S] pharmacological profile on both
      sites permitted to classify the high affinity binding site as representative of
      the purinergic P2Y(1) receptor subtype and the low affinity binding site of the
      P2Y(4) and/or P2Y(6) receptor subtypes. ATP-alpha-S and Adenosine-5'-O-(2
      thiodiphosphate) (ADP-beta-S) exhibited opposite selectivity on high and low
      affinity binding sites. Although purinergic P2Y(1) receptor, or a P2Y(1)-like
      subtype, has been generally considered as that implicated in the modulation of
      glucose-induced insulin release, the present data show that the beta-cell
      expresses a complex profile of purinergic P2Y receptor subtypes, the functional
      implication of which remains to be fully elucidated.

PMID- 17509561
TI  - NMDA receptors of dorsal hippocampus are involved in the acquisition, but not in
      the expression of morphine-induced place preference.
AB  - In the present study, involvement of the N-methyl-d-aspartate (NMDA) receptors of
      the CA1 region of dorsal hippocampus (intra-CA1) in the acquisition or expression
      of morphine-induced conditioned place preference in rats was studied. Male Wistar
      rats were used in these experiments. NMDA-receptor agonist (NMDA) and antagonist
      (MK-801) were injected into the CA1 region of the dorsal hippocampus (intra-CA1)
      and morphine was injected subcutaneously. An unbiased conditioned place
      preference paradigm was used to study the effect of these agents. In the first
      set of experiments, the drugs were used during the development of conditioned
      place preference by morphine or they were used alone in order to see if they
      induce conditioned place preference or conditioned place aversion. Our data
      showed that subcutaneous (s.c.) injection of morphine sulphate (2.5-10 mg/kg)
      induced conditioned place preference in rat. NMDA (0.1-1 microg/rat) or MK-801 (1
      4 microg/rat) did not induce conditioned place preference or conditioned place
      aversion. Intra-CA1 administration of different doses of NMDA (0.1-1 microg/rat)
      increased, while MK-801 (1-4 microg/rat) decreased morphine-induced place
      preference. MK-801 reversed the effect of NMDA on morphine response. In the
      second set of experiments, when the drugs were used before testing on Day 5, in
      order to test their effects on the expression of morphine (7.5 mg/kg)-induced
      place preference, intra-CA1 administration of NMDA or MK-801 did not alter the
      morphine response. None of the drugs influenced locomotion. It is concluded that
      NMDA receptor of the CA1 region of hippocampus are involved in the acquisition
      but not expression of morphine-induced place preference.

PMID- 17509562
TI  - Importance of intracellular angiotensin II in vascular smooth muscle cell
      apoptosis: inhibition by the angiotensin AT1 receptor antagonist irbesartan.
AB  - The intracellular uptake of Angiotensin II has been described, although its
      physiological role is not yet understood. We aimed to study the role of
      Angiotensin II internalization in Angiotensin II-induced apoptosis. Vascular
      smooth muscle cells were cultured from male Wistar-Kyoto rats and treated with
      Angiotensin II (1 microM, 48 h). Apoptosis was assessed by DNA fragmentation,
      cell cytometry and caspase-3 activity. The Angiotensin AT(1) receptor antagonist
      irbesartan (0.1-10 microM) and the inhibitors of Angiotensin II internalization
      phenylarsine oxide (PAO, 20 microM), but not the AT(2) receptor antagonist
      PD123319 (S-(+)-1-[(4-(Dimethylamino)-3-methylphenyl)methyl]-5-(diphenylacetyl)
      4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid
      di(trifluoroacetate) salt), decreased Angiotensin II-mediated apoptosis. Pre
      treatment with irbesartan, but not with PD123319, blocked Angiotensin II
      internalization. We found a strong correlation between intracellular Angiotensin
      II staining and Angiotensin II-induced apoptosis for all compared groups. We
      therefore conclude that internalization of Angiotensin II is involved in
      apoptosis of vascular smooth muscle cells induced by this peptide.

PMID- 17509564
TI  - Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose)
      glycohydrolase (PARG) activity.
AB  - Poly(ADP-ribose)glycohydrolase (PARG) is the major enzyme capable of rapidly
      hydrolyzing poly(ADP-ribose) (PAR) formed by the diverse members of the PARP
      enzyme family. This study presents an alternative splice mechanism by which two
      novel PARG protein isoforms of 60 kDa and 55 kDa are expressed from the human
      PARG gene, termed hPARG60 and hPARG55, respectively. Homologous forms were found
      in the mouse (mPARG63 and mPARG58) supporting the hypothesis that expression of
      small PARG isoforms is conserved among mammals. A PARG protein of approximately
      60 kDa has been described for decades but with its genetic basis unknown, it was
      hypothesized to be a product of posttranslational cleavage of larger PARG
      isoforms. While this is not excluded entirely, isolation and expression of cDNA
      clones from different sources of RNA indicate that alternative splicing leads to
      expression of a catalytically active hPARG60 in multiple cell compartments. A
      second enzyme, hPARG55, that can be expressed through alternative translation
      initiation from hPARG60 transcripts is strictly targeted to the mitochondria.
      Functional studies of a mitochondrial targeting signal (MTS) in PARG exon IV
      suggest that hPARG60 may be capable of shuttling between nucleus and
      mitochondria, which would be in line with a proposed function of PAR in genotoxic
      stress-dependent, nuclear-mitochondrial crosstalk.

PMID- 17509565
TI  - Impaired mitochondrial Ca2+ homeostasis in respiratory chain-deficient cells but
      efficient compensation of energetic disadvantage by enhanced anaerobic glycolysis
      due to low ATP steady state levels.
AB  - Energy-producing pathways, adenine nucleotide levels, oxidative stress response
      and Ca(2+) homeostasis were investigated in cybrid cells incorporating two
      pathogenic mitochondrial DNA point mutations, 3243A>G and 3302A>G in
      tRNA(Leu(UUR)), as well as Rho(0) cells and compared to their parental 143B
      osteosarcoma cell line. All cells suffering from a severe respiratory chain
      deficiency were able to proliferate as fast as controls. The major defect in
      oxidative phosphorylation was efficiently compensated by a rise in anaerobic
      glycolysis, so that the total ATP production rate was preserved. This enhancement
      of glycolysis was enabled by a considerable decrease of cellular total adenine
      nucleotide pools and a concomitant shift in the AMP+ADP/ATP ratios, while the
      energy charge potential was still in the normal range. Further important
      consequences were an increased production of superoxide which, however, was
      neither escorted by major changes in the antioxidative defence systems nor was it
      leading to substantial oxidative damage. Most interestingly, the lowered
      mitochondrial membrane potential led to a disturbed intramitochondrial calcium
      homeostasis, which most likely is a major pathomechanism in mitochondrial
      diseases.

PMID- 17509566
TI  - Muscle intermediate filaments and their links to membranes and membranous
      organelles.
AB  - Intermediate filaments (IFs) play a key role in the integration of structure and
      function of striated muscle, primarily by mediating mechanochemical links between
      the contractile apparatus and mitochondria, myonuclei, the sarcolemma and
      potentially the vesicle trafficking apparatus. Linkage of all these membranous
      structures to the contractile apparatus, mainly through the Z-disks, supports the
      integration and coordination of growth and energy demands of the working myocyte,
      not only with force transmission, but also with de novo gene expression, energy
      production and efficient protein and lipid trafficking and targeting. Desmin, the
      most abundant and intensively studied muscle intermediate filament protein, is
      linked to proper costamere organization, myoblast and stem cell fusion and
      differentiation, nuclear shape and positioning, as well as mitochondrial shape,
      structure, positioning and function. Similar links have been established for
      lysosomes and lysosome-related organelles, consistent with the presence of
      widespread links between IFs and membranous structures and the regulation of
      their fusion, morphology and stabilization necessary for cell survival.

PMID- 17509567
TI  - Estradiol augments peri-infarct cerebral vascular density in experimental stroke.
AB  - Peri-infarct increase of vascular density has been observed in animals and in
      humans with ischemic stroke. Increased peri-infarct vascular density correlates
      with improved functional outcome after stroke. We hypothesized that pre-treatment
      with estradiol will increase post-ischemic peri-infarct capillary density in a
      rat model of transient ischemic stroke. Estradiol, compared to placebo, augmented
      post-ischemic peri-infarct vascular density by 22% 10 days after stroke. Recovery
      of forelimb function was not improved with estradiol treatment on day three and
      nine post-stroke. Loss of estradiol may limit repair in the peri-infarct region
      by limiting angiogenesis, but functional significance in stroke recovery requires
      further investigation.

PMID- 17509568
TI  - The complex aetiology of frontotemporal lobar degeneration.
AB  - Frontotemporal lobar degeneration (FTLD) is now a widely recognised form of
      dementia. This heterogeneous disease has been of particular interest to
      geneticists due to its high rate of heritability with up to 40% of patients
      reporting a family history of the disease in at least one extra family member.
      There have been several chromosome loci linked to this disorder and three genes
      have already been identified. Remarkably, it has been recently demonstrated that
      2 of these are only 1.7 Mb from one another on chromosome 17q21, these being tau
      and progranulin. The identification of these genes has contributed greatly to our
      understanding of the differing neuropathologies associated with FTLD.
      Furthermore, the discovery that TDP-43 is a component of the neuronal inclusions
      seen in the most common neuropathological subtype has also helped expand the
      biochemical pathways that are the focus of much FTLD research. Nevertheless,
      other genes causing FTLD remain to be identified and their biology elucidated
      before we have a complete understanding of the complex aetiology of this disease.

PMID- 17509569
TI  - Nuclear export and cytoplasmic maturation of ribosomal subunits.
AB  - Based on the characterization of ribosome precursor particles and associated
      trans-acting factors, a biogenesis pathway for the 40S and 60S subunits has
      emerged. After nuclear synthesis and assembly steps, pre-ribosomal subunits are
      exported through the nuclear pore complex in a Crm1- and RanGTP-dependent manner.
      Subsequent cytoplasmic biogenesis steps of pre-60S particles include the
      facilitated release of several non-ribosomal proteins, yielding fully functional
      60S subunits. Cytoplasmic maturation of 40S subunit precursors includes rRNA
      dimethylation and pre-rRNA cleavage, allowing 40S subunits to achieve translation
      competence. We review current knowledge of nuclear export and cytoplasmic
      maturation of ribosomal subunits.

PMID- 17509570
TI  - Osteosarcoma cell-calcium signaling through tissue factor-factor VIIa complex and
      factor Xa.
AB  - The cells responsible for bone formation express protease-activated receptors.
      Although serine protease thrombin has been shown to elicit functional responses
      in bone cells that impact on cell survival and alkaline phosphatase activity,
      nothing is known about tissue factor, factor VIIa, and factor Xa, the serine
      proteases that act upstream of thrombin in the coagulation cascade. This paper
      demonstrates that tissue factor is expressed in the osteoblast-like cell line
      SaOS-2 and, that tissue factor in a factor VIIa-bound complex induces a transient
      intracellular Ca(2+) increase through protease-activated receptor-2. In SaOS-2
      cells, factor Xa induced a sustained intracellular Ca(2+) response, as does
      SLIGRL, a PAR2-activating peptide, and PAR-1-dependent cell viability.

PMID- 17509571
TI  - Stress and prions: lessons from the yeast model.
AB  - Yeast self-perpetuating amyloids (prions) provide a convenient model for studying
      the cellular control of highly ordered aggregates involved in mammalian protein
      assembly disorders. The very ability of an amyloid to propagate a prion state in
      yeast is determined by its interactions with the stress-inducible chaperone
      Hsp104. Prion formation and propagation are also influenced by other stress
      related chaperones (Hsp70 and Hsp40), and by alterations of the protein
      trafficking and degradation networks. Some stress conditions induce prion
      formation or loss. It is proposed that prions arise as byproducts of the
      reversible assembly of highly ordered complexes, protecting certain proteins
      during unfavorable conditions.

PMID- 17509572
TI  - Afr1p has a role in regulating the localization of Mpk1p at the shmoo tip in
      Saccharomyces cerevisiae.
AB  - Afr1p functions to promote adaptation to pheromone-induced growth arrest and
      morphogenesis. We show here that Afr1p regulates polarized localization of the
      Mpk1p MAP kinase in shmooing cells. Deletion of AFR1 results in mislocalization
      of Mpk1p although the scaffold protein Spa2p localizes normally at shmoo tip, and
      overexpression of Spa2 cannot rescue this defect, indicating Afr1p in required
      for Spa2p to recruit Mpk1 to the site of polarized growth during mating.
      Overexpression of SPA2 partially suppresses the morphogenetic defect of afr1Delta
      cells upon alpha-factor induction, suggesting the two proteins function in the
      same genetic pathway with Spa2p acts downstream of Afr1p.

PMID- 17509573
TI  - Analysis of the rainbow trout solute carrier 11 family reveals iron import < or =
      pH 7.4 and a functional isoform lacking transmembrane domains 11 and 12.
AB  - A Xenopus oocyte heterologous expression system was used to characterise iron
      transport properties of two members of the solute carrier 11 (slc11) protein
      family isolated from rainbow trout gills. One cDNA clone differed from the trout
      Slc11alpha containing an additional 52bp in the exon between transmembrane
      domains (TM) 10 and 11. The 52bp contained a stop codon, resulting in a novel
      isoform lacking the last two TM (termed slc11gamma). Slc11gamma and another
      isoform slc11beta, import Fe(2+) at external pHs < or = to 7.4. Trout slc11beta
      Fe(2+) import was more sensitive to inhibition by divalent metals. The novel
      vertebrate slc11gamma isoform functions without TM11 and 12.

PMID- 17509574
TI  - A single amino acid in the PSPG-box plays an important role in the catalytic
      function of CaUGT2 (Curcumin glucosyltransferase), a Group D Family 1
      glucosyltransferase from Catharanthus roseus.
AB  - Curcumin glucosyltransferase (CaUGT2) isolated from cell cultures of Catharanthus
      roseus exhibits unique substrate specificity. To identify amino acids involved in
      substrate recognition and catalytic activity of CaUGT2, a combination of domain
      swapping and site-directed mutagenesis was carried out. Exchange of the PSPG-box
      of CaUGT2 with that of NtGT1b (a phenolic glucosyltransferase from tobacco) led
      to complete loss of enzyme activity in the resulting recombinant protein.
      However, replacement of Arg378 of the NtGT1b PSPG-box with cysteine, the
      corresponding amino acid in CaUGT2, restored the catalytic activity of the
      chimeric enzyme. Further site-directed mutagenesis revealed that the size of the
      amino acid side-chain in that particular site is critical to the catalytic
      activity of CaUGT2.

PMID- 17509575
TI  - Aneuploidy in the miscarriages of infertile women and the potential benefit of
      preimplanation genetic diagnosis.
AB  - OBJECTIVE: To evaluate the frequency of specific aneuploidies in miscarriages in
      an infertility practice and calculate the potential sensitivities of the
      different aneuploidy screening options for preimplantation genetic diagnosis
      (PGD) in this setting. DESIGN: Retrospective analysis. SETTING: Academic
      reproductive endocrinology and infertility practice. PATIENT(S): Women with
      miscarriages that had karyotype analysis on products of conception.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Karyotype of spontaneous
      abortions compared with commercially available PGD options. RESULT(S): Of the 273
      karyotypes analyzed, 177 (64.8%) were abnormal. The average age of the patients
      was 37 +/- 4.5 years. Using a limited five-probe panel, 54 of the 177 (31%)
      abnormal karyotypes would have been detected. In contrast, an extended PGD panel
      (using 9, 10, or 12 chromosome probes) would have detected 127, 131, and 140 of
      177 abnormalities, 72%, 74%, and 79% respectively. The difference between the
      limited (5-probe) and extended (9-, 10-, and 12-probe) panels was statistically
      significant. There was not a statistically significant difference among the
      extended panels. CONCLUSION(S): Most of the abnormalities seen in miscarriages
      are detectable by PGD with extended panels. A significantly higher percentage of
      these abnormalities could be detected by screening for 9, 10, or 12 chromosomes
      compared with only 5.

PMID- 17509576
TI  - Location of the embryo-transfer catheter guide before the internal uterine os
      improves the outcome of in vitro fertilization.
AB  - The objective of this study was to assess whether positioning the embryo transfer
      (ET) catheter guide at the time of embryo expulsion, before or beyond the
      internal os, has an impact on IVF cycle outcome. We performed a retrospective
      study comparing IVF outcomes in relation to the ET guide position relative to the
      internal uterine os. We analyzed ultrasound-guided ETs in IVF-intracytoplasmic
      sperm injection (ICSI) cycles, performed with the tip of the ET catheter guide
      just before the internal os (group 1) and beyond the internal os (group 2).
      Implantation and pregnancy rates were significantly better in group 1 than in
      group 2, at 14.8% versus 11.8% and 57.3% versus 43.1, respectively. We conclude
      that passing the ET catheter guide beyond the internal os reduces implantation
      and pregnancy rates.

PMID- 17509577
TI  - Association between birth weight and first-trimester free beta-human chorionic
      gonadotropin and pregnancy-associated plasma protein A.
AB  - STUDY OBJECTIVE: To assess the relationship between first-trimester maternal
      serum PAPP-A and free beta-hCG and birth weight. DESIGN: Observational study.
      SETTING: Teaching hospital. PATIENT(S): Singleton pregnancies (n = 1,630) at 10
      14 weeks of gestation. INTERVENTION(S): Fluorimetric immunoassays for maternal
      serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG. MAIN
      OUTCOME MEASURE(S): Customized birth weight percentiles, calculated taking into
      account maternal height, weight, ethnic origin, parity, smoking status, and fetal
      gender. RESULT(S): There was a significant positive correlation between birth
      weight and PAPP-A, but not free beta-hCG levels. Maternal serum levels of PAPP-A
      were significantly lower in small-for-gestation (SGA) newborns than in control
      subjects and were significantly higher in large-for-gestation (LGA) newborns than
      in control subjects. Maternal serum free beta-hCG levels were lower in
      pregnancies complicated by pre-eclampsia than in normotensive ones. Multivariable
      analysis found PAPP-A to be an independent predictor of absolute birth weight,
      SGA, and LGA. Free beta-hCG was found to be an independent predictor of
      gestational hypertension and pre-eclampsia. Neither of the two markers was
      associated with preterm delivery. CONCLUSION(S): Maternal serum PAPP-A levels in
      the late first trimester of pregnancy are associated with subsequent fetal growth
      (including both physiologic variation and abnormal growth), and decreased free
      beta-hCG is more predictive of hypertensive disorders of pregnancy.

PMID- 17509578
TI  - Soluble HLA-G in the peritoneal fluid of women with endometriosis.
AB  - The aim of this study was to determine the level of soluble HLA-G molecules in
      the peritoneal fluid of endometriosis patients. The findings demonstrate that a
      soluble HLA-G level in the peritoneal fluid of women with endometriosis is
      similar to that of the control group.

PMID- 17509579
TI  - Infertility surgery is dead: only the obituary remains?
AB  - Despite the multiple advantages of assisted reproductive technology compared with
      surgery, there remain several diagnoses for which surgery is still widely
      performed: distal tubal occlusion, regret of permanent sterilization, and
      endometriosis. Assisted reproductive technology is superior to surgery and should
      be offered as first-line treatment.

PMID- 17509580
TI  - Estro-progestin supplementation enhances the growth hormone secretory
      responsiveness to ghrelin infusion in postmenopausal women.
AB  - OBJECTIVE: To assess the effects of estro-progestin supplementation on ghrelin
      mediated GH release, we studied the consequence of ghrelin or saline injection
      before and after 60 days of hormone therapy or placebo administration in
      postmenopausal subjects. DESIGN: A prospective double blind, placebo-controlled,
      and parallel cohort study. SETTING: Catholic University of Sacred Heart,
      Operative Division of Endocrinological Gynecology. PATIENT(S): Eighteen
      postmenopausal women participated in the study. INTERVENTION(S): Ten women were
      randomized to receive estro-progestin treatment (2 mg of hemihydrate E(2) and 10
      mg of dydrogesterone in a continuous sequential regimen); eight women were
      treated with placebo. All patients underwent in a randomized order a ghrelin test
      (1 microg/kg IV bolus) or a saline infusion (2-mL IV bolus) on two different
      days, before and after 60 days of treatment. MAIN OUTCOME MEASURE(S): Basal
      hormonal assays, including ghrelin basal levels. The GH levels were measured at
      baseline and after 15, 30, 60, 90 minutes of ghrelin or saline injection.
      RESULT(S): The acute ghrelin injection released a notable GH secretion in all
      postmenopausal women. After estro-progestin therapy the ghrelin-stimulated GH
      response was significantly higher than before treatment. In particular, the
      percent increase of ghrelin GH-releasing effect, expressed as incremental area
      under the curve (AUCi-GH) was more than 50% after hormone therapy. CONCLUSION(S):
      In postmenopausal women estro-progestin treatment clearly influenced the ghrelin
      stimulated GH secretion.

PMID- 17509581
TI  - Survivin gene expression in granulosa cells from infertile patients undergoing in
      vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To evaluate survivin gene expression in granulosa cells from infertile
      patients and examine the relationship between survivin gene expression and
      infertile clinical background. DESIGN: Prospective study. SETTING: IVF-ET program
      at Osaka Medical College. PATIENT(S): Twenty-eight patients underwent ovulation
      induction for IVF-ET performed because of tubal infertility, male factor
      infertility, or endometriosis. INTERVENTION(S): Granulosa cells obtained at
      oocyte retrieval were examined for survivin gene expression by quantitative
      reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURE(S): Hormone
      environment, number of oocytes, fertilization rate, high-quality embryo rate,
      pregnancy rate, and expression of survivin genes. RESULT(S): Survivin gene
      expression was detected in all granulosa cells. The gene expression levels of
      survivin in patients with endometriosis were significantly lower than those in
      patients with male factor infertility. The gene expression levels of survivin in
      total pregnant patients were higher than those in total nonpregnant patients and
      than those in the male factor infertility group, and there was no correlation
      between gene expression level and serum E(2) level. CONCLUSION(S): Survivin may
      be used as an indicator of the success of IVF-ET, and the existence of
      endometriosis may elevate the apoptosis of granulosa cells.

PMID- 17509582
TI  - Potato aspartic proteases (StAPs) exert cytotoxic activity on bovine and human
      spermatozoa.
AB  - OBJECTIVE: To evaluate the in vitro spermicidal activity of Solanum tuberosum
      aspartic proteinases (StAPs) on bovine and human sperm. DESIGN: Controlled
      laboratory study. SETTING: Three research laboratories at a university of
      biologic science. ANIMAL(S) AND DONOR(S): Frozen semen from five Aberdeen Angus
      bulls and six proven fertile men volunteers. INTERVENTION(S): The effect of StAPs
      on sperm motility was studied in vitro by incubation of different concentrations
      of StAPs with sperm suspensions, and motility was assessed by direct microscopic
      observation. Membrane integrity was analyzed by SYTOX Green uptake after
      incubation with different StAP concentrations. The effect of StAPs was evaluated
      by human erythrocyte lysis, as a control in somatic cells. The StAPs binding was
      monitored by fluorescence. MAIN OUTCOME MEASURE(S): Total and progressive sperm
      motility; hypoosmotic swelling test and SYTOX Green uptake as a measure of
      membrane damage; fluorescein isothiocyanate-labeled StAP binding by an optical
      microscopy. RESULT(S): The StAPs reduced sperm motility in a dose-dependent
      manner, and 25 microM of StAP1 and 35 microM of StAP3 completely abolished the
      progressive motility. The StAPs were able to bind in the postacrosomal and
      midpiece region only in bovine sperm. Also, StAPs caused spermatozoa
      agglutination. In vitro cell toxicity was observed by a dose-dependent increase
      in hypoosmotic swelling negative sperm and SYTOX Green uptake in both human and
      bovine spermatozoa; however, no toxic effect was observed on erythrocytes.
      CONCLUSION(S): The spermicidal effect of StAPs involves plasma membrane
      permeabilization.

PMID- 17509583
TI  - Early embryo cleavage and day 2 mononucleation after intracytoplasmatic sperm
      injection for predicting embryo implantation potential in single embryo transfer
      cycles.
AB  - In this study we analyzed the outcome of 275 fresh single embryo transfer cycles
      of day 2, mononucleate four-cell preembryos that had either cleaved early (n =
      175) or not cleaved early (n = 100) 25 to 28 hours after intracytoplasmatic sperm
      injection. Neither the implantation rate nor the delivery rate showed any
      difference between the two groups, indicating that when a top-quality preembryo
      (mononucleate four-cell preembryo on day 2) is transferred, the presence of early
      cleavage seems to add no additional advantage in predicting the implantation
      potential of the preembryo.

PMID- 17509584
TI  - Effect of vaginal lubricants on sperm motility and chromatin integrity: a
      prospective comparative study.
AB  - OBJECTIVE: To evaluate the effect of vaginal lubricants Pre-Seed, FemGlide,
      Astroglide, and Replens on human sperm motility and chromatin integrity. DESIGN:
      Prospective, comparative, in vitro study. SETTING: Andrology laboratory at
      tertiary care hospital. PATIENT(S): Thirteen normozoospermic donors.
      INTERVENTION(S): Semen samples from 13 subjects were incubated in human tubal
      fluid media (HTF) controls and 10% (vol/vol) of Pre-Seed, FemGlide, Astroglide,
      and Replens lubricants. After 30 minutes, progressive sperm motility was assessed
      by light microscopy. Semen samples of 12 patients were placed in positive control
      (HTF), negative control (10% K-Y Jelly lubricant), and 10% vol/vol Pre-Seed and
      FemGlide lubricants. After 4 hours culture, spermatozoa were analyzed for percent
      DNA fragmentation index with use of the acridine orange-based sperm chromatin
      structure assay. MAIN OUTCOME MEASURE(S): Sperm motility and percent DNA
      fragmentation index. RESULTS: Percent motility did not differ significantly
      between HTF controls and Pre-Seed, whereas FemGlide, Replens, and Astroglide
      lubricants demonstrated a significant decrease in motility. There was no
      significant difference in percent DNA fragmentation index between the HTF
      controls and Pre-Seed, but a significant decline in sperm chromatin quality
      occurred with FemGlide and K-Y Jelly. CONCLUSION: Pre-Seed does not cause a
      significant decrease in progressive sperm motility or chromatin integrity in
      contrast to other lubricants used by couples.

PMID- 17509586
TI  - Elective single blastocyst transfer in women older than 35.
AB  - A retrospective review of all patients older than 35 who underwent elective
      single blastocyst transfer was performed. Twenty-three of the 45 patients (51.1%)
      have an ongoing pregnancy or liveborn delivery, with a mean age of 37.3 years,
      demonstrating a clear role for elective single transfer in this relatively older
      IVF population.

PMID- 17509587
TI  - Normalization of serum luteinizing hormone levels in women with 46,XX spontaneous
      primary ovarian insufficiency.
AB  - OBJECTIVE: To determine the proportion of women with primary ovarian
      insufficiency who achieve normal serum LH levels on transdermal E(2) therapy.
      DESIGN: Prospective. SETTING: Clinical research center at a national US health
      research facility. PATIENT(S): Women with spontaneous primary ovarian
      insufficiency (n = 137) and 70 regularly menstruating control women (n = 70).
      INTERVENTION(S): Blood sampled from controls in the midfollicular phase and from
      patients while they were off E(2) for 2 weeks, then again 3 months later during
      the E(2)-only phase of hormone therapy (E(2) patch [100 microg/d] and oral
      medroxyprogesterone acetate [10 mg for 12 d/mo]). MAIN OUTCOME MEASURE(S): Serum
      LH. RESULT(S): While on transdermal E(2) therapy, significantly more women
      (51.1%, 70/137; 95% confidence interval, 42%, 60%) had serum LH levels in the
      normal range (5/137, 3.9% at baseline). Mean (SD) serum E(2) level significantly
      increased on therapy to 95.4 (84.9) pg/mL. CONCLUSION(S): A regimen of 100
      microg/d of transdermal E(2) therapy achieves normal serum LH levels in
      approximately one half of women with spontaneous primary ovarian insufficiency.
      Theoretically, by avoiding inappropriate luteinization, physiologic E(2) therapy
      may improve follicle function in these women. Controlled studies to assess the
      effect of transdermal E(2) therapy on follicle function in these women are
      warranted.

PMID- 17509588
TI  - 17beta-hydroxysteroid dehydrogenase 3 deficiency in a male pseudohermaphrodite.
AB  - OBJECTIVE: To present the clinical, biochemical, and genetic features of a male
      pseudohermaphrodite whose condition was caused by 17beta-hydroxysteroid
      dehydrogenase 3 (17beta-HSD3) deficiency. DESIGN: Case report. SETTING:
      Gynecology practice in a university teaching hospital. PATIENT(S): A 15-year-old
      black American male pseudohermaphrodite with 17beta-HSD3 deficiency.
      INTERVENTION(S): Laboratory evaluation, genetic mutation analysis, bilateral
      gonadectomy, and hormone replacement. MAIN OUTCOME MEASURE(S): Endocrinologic
      evaluation and genetic analysis. RESULT(S): A diagnosis of 17beta-HSD3 deficiency
      made on the basis of hormone evaluation was confirmed through genetic mutation
      analysis of the HSD17B3 gene. Female phenotype was attained after gonadectomy,
      passive vaginal dilatation, and hormone therapy. CONCLUSION(S): Deficiency of
      17beta-HSD3 was diagnosed in this patient on the basis of endocrinologic
      evaluation and was confirmed with genetic mutation analysis. The patient was able
      to retain her female sexual identity after surgical and medical treatment.

PMID- 17509589
TI  - Assessment of myoelectrical signal parameters in estrogen, progesterone, and
      human chorionic gonadotropin administered in nonpregnant rat myometrium after
      ovariectomy.
AB  - OBJECTIVE: To investigate the correlation of myoelectrical signals with
      spontaneous contractile events and physiological states in the nonisolated
      uterine horn of rats. DESIGN: In vivo uterine myoelectrical activity recording
      study. SETTING: Animal and pharmacology laboratory at Inonu University.
      ANIMAL(S): Thirty-six female Wistar albino rats. INTERVENTION(S): Six animals
      were not castrated and served as a sham-operated control group; the other 30 were
      ovariectomized (OVX) and put into groups: unbiased OVX subjects, estrogen (E)
      biased OVX subjects, P-biased OVX subjects, E-plus-P-biased OVX subjects, and hCG
      biased OVX subjects. An MP100 A-CE was used for data acquisition, and a personal
      computer was used for processing. MAIN OUTCOME MEASURE(S): Besides the temporal,
      spectral, and joint time-frequency (spectrotemporal) analysis, some quantitative
      measures such as standard deviation and mark to space power ratios of
      myoelectrical signals were measured. RESULT(S): Progesterone, E, and hCG
      administration down-regulated the power and contraction frequency of the uterine
      electrical signal. The spectral concentrations that occurred around the 0.9,
      0.35, and 0.7 Hz frequency ranges may be distinguishing characteristics for P, E,
      and hCG, respectively. CONCLUSION(S): Based on the obtained results, uterine
      contractions change with ovariectomy and administration of hormones.
      Progesterone, E, and hCG particularly prolong the quiescent periods of the uterus
      by reducing the frequency of uterine contractions as well as the power of the
      myoelectrical activity. Individual or combined use of P, E, or hCG might favor
      quiescence of the uterine muscle and the maintenance of pregnancy.

PMID- 17509590
TI  - Development of a rapid, sensitive, and reproducible laboratory test kit for the
      assessment of plasma membrane integrity of human sperm.
AB  - OBJECTIVE: To develop a rapid, sensitive, and reproducible hypoosmotic swelling
      test kit for the assessment of plasma membrane integrity of human sperm in vitro.
      DESIGN: Prospective comparison of results with the World Health Organization
      (WHO) method, performed simultaneously. SETTING: Infertility center in a major
      city in India. PATIENT(S): Couples who presented for infertility evaluation.
      INTERVENTION(S): The sperm tail-coiling pattern representing sperm plasma
      membrane integrity was analyzed by using different concentrations of NaCl and
      also with plain double distilled water (ddH(2)O). Hypoosmotic swelling solution
      with 2% NaCl in ddH(2)O equivalent to 68 Osm/L was selected for further analysis
      because it provided the highest and the qualitatively best type (g) of tail
      coiling among the various other options tried in comparison. MAIN OUTCOME
      MEASURE(S): A rapid laboratory test kit for the assessment of plasma membrane
      integrity of sperm was developed that is equally sensitive and reproducible as
      that described in the WHO protocol. The test was validated by using different
      normal and subnormal semen samples and in comparison with the standard WHO
      protocol. RESULT(S): After the screening with different hypoosmotic solutions by
      using semen samples from fertile volunteers, NaCl (2%) provided the highest and
      the best types of typical tail coiling, characteristic of sperm with good plasma
      membrane integrity. The study was then extended to 60 normozoospermic semen
      samples, which demonstrated a hypoosmotic swelling response of 69.5% +/- 5.23%
      and 71.5% +/- 4.89%, as per WHO or the present modified method, respectively
      (coefficient of correlation, r = 0.741). In 13 oligospermic and 18
      teratozoospermic subjects, the hypoosmotic swelling response of sperm as per the
      new method were 36.4% +/- 5.75% and 34.2% +/- 7.78%, respectively, which were
      comparable to those obtained through the WHO method. There was a 15% drop in
      viability of sperm after the hypoosmotic challenge (5 min), irrespective of the
      hypoosmotic solution used. No other morphological alterations in sperm were
      observed after the hypoosmotic challenge. CONCLUSION(S): The new test kit can be
      used routinely in laboratories for assessment of plasma membrane integrity of
      sperm in vitro.

PMID- 17509591
TI  - Visualization of cytoskeleton components during fertilization in mammals.
AB  - The authors analyzed the cytoskeletal dynamics during human and bovine
      fertilization. Microtubules, microfilaments, and actin-related proteins are
      differently required for pronuclear migration and apposition.

PMID- 17509592
TI  - The effects of raloxifen on depression and cognition in ovariectomized rats.
AB  - This study investigates the effects of raloxifen on cognition and depression in
      an animal model.

PMID- 17509593
TI  - Aspirin in women undergoing in vitro fertilization treatment: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: Many trials have evaluated the effects of aspirin in women undergoing
      IVF or intracytoplasmic sperm injection (ICSI) treatment. These trials have
      generally shown inconclusive or inconsistent findings. We conducted a systematic
      review of trials of aspirin during IVF or ICSI treatment to generate more precise
      estimates of effects and attempt to explore the reasons for the inconsistencies.
      DESIGN: A systematic review and meta-analysis. SETTING: Assisted conception units
      in different countries. PATIENT(S): Seven trials including 1,241 women undergoing
      controlled ovarian hyperstimulation (COH), IVF, or ICSI and day 3 embryo
      transfer. INTERVENTION(S): Low-dose aspirin supplementation versus placebo or no
      supplementation. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth.
      RESULT(S): Searches were conducted in MEDLINE, EMBASE, Cochrane Library, ISI
      Proceedings, and SCISEARCH, and all randomized controlled trials that evaluated
      the effectiveness of aspirin compared to placebo or no treatment in women
      undergoing IVF-ICSI treatment were included. Study selection, quality appraisal,
      and data extractions were performed independently and in duplicate. Seven
      relevant trials were identified. Meta-analysis of these studies did not show a
      significant benefit of aspirin therapy in improving clinical pregnancy rate
      (relative risk [RR] 1.11, 95% confidence interval [CI] 0.95, 1.31) or live birth
      rate (RR 0.94, 95% CI 0.64, 1.39). There was no significant difference in
      miscarriage rate (RR 1.06, 95% CI 0.53, 2.11) or ectopic pregnancy rate (RR 2.24,
      95% CI 0.70, 7.24). An improvement was noted in uterine artery pulsatility index
      (weighted mean difference: -0.78, 95% CI -0.87, -0.69) in women taking low-dose
      aspirin. The evidence regarding other outcomes was either not significant or
      contradictory. CONCLUSION(S): Currently available evidence does not support the
      use of aspirin in IVF or ICSI treatment. However, the noted trend of improvement
      in clinical pregnancy, and the lack of power even when the studies were pooled
      highlight the need for a definitive trial.

PMID- 17509594
TI  - Cryopreservation of supernumerary high quality embryos predicts favorable
      outcomes for patients undergoing repeated cycles of in vitro fertilization.
AB  - OBJECTIVE: To determine whether the decline in pregnancy and implantation rates
      in repeated fresh IVF cycles is associated with the availability of embryo
      cryopreservation. DESIGN: Retrospective study. SETTING: Assisted reproductive
      unit at an academic institution. PATIENT(S): Women <38 years old (1,037),
      undergoing nondonor fresh or frozen embryo transfer (FET) cycles between January
      1, 2000 and December 31, 2005. INTERVENTION(S): In fresh cycles, women used
      either pituitary desensitization or GnRH antagonists in combination with
      gonadotropin stimulation protocols before oocyte retrieval. In FET cycles,
      endometrial development was achieved by oral E(2) and vaginal P after pituitary
      desensitization. Embryo transfer occurred either on day 3 or on day 5. MAIN
      OUTCOME MEASURE(S): Implantation and pregnancy rates (PR). RESULT(S): Excluding
      FET cycles, implantation rates and PRs declined significantly in repeated cycles
      compared to the initial one. However, women with supernumerary embryos for
      cryopreservation appeared to produce embryos with higher implantation potential
      but were excluded from the analysis. When FET cycles were included, there were no
      significant declines in PRs for at least three repeated cycles. CONCLUSION(S):
      Embryo cryopreservation stratifies women with high quality embryos from those
      with low quality embryos who require repeat fresh attempts, resulting in an
      accelerated decline in observed PRs and implantation rates.

PMID- 17509596
TI  - The content and effects of palliative care courses for nurses: a literature
      review.
AB  - OBJECTIVES: The present literature review describes the literature (1990-2005)
      that concerns the effects of courses in palliative care at the pre- and
      postgraduate levels. DATA SOURCES: A search was made for literature from the
      period between 1990 and 2005 using CINAHL, Pubmed and Psychlit, supplemented with
      a search for relevant systematic reviews from the Cochrane Library. DESIGN: The
      research questions were directed on the areas of expertise and skills, the
      didactical methods, the effects of the courses and the standards to measure these
      effects. RESULTS: The studies were all focused on general palliative care. Out of
      27 studies 21 reported positive effects for communication, attitude, empathy and
      pain. Six of these 21 positive trails were studies with good quality designs,
      whereas 15 had moderate designs. The six studies with a lack of effects was one
      study with good quality and five studies with moderate quality designs. The
      effects on patients were described in only a few cases. There was still frequent
      use of self-constructed rating scales, where data about validity and reliability
      were lacking or where these aspects were not studied. CONCLUSIONS: The most
      successful were integrated courses focused on several themes with a variety of
      didactical methods.

PMID- 17509595
TI  - Androgens and eye movements in women and men during a test of mental rotation
      ability.
AB  - Eye movements were monitored in 16 women and 20 men during completion of a
      standard diagram-based test of mental rotation ability to provide measures of
      cognitive function not requiring conscious, decisional processes. Overall, women
      and men allocated visual attention during task performance in very similar,
      systematic ways. However, consistent with previous suggestions that sex
      differences in attentional processes during completion of the mental rotation
      task may exist, eye movements in men compared to women indicated greater
      discrimination and longer processing of correct alternatives during task
      performance. Other findings suggested that androgens may enhance cognitive
      processes that are recruited differentially by women and men as a function of the
      task. Specifically, smaller (i.e., more masculine) digit ratios were associated
      with men's shorter fixations on distracters, suggesting that perinatal androgen
      action may influence brain systems that facilitate the identification of relevant
      task stimuli. In women, higher circulating testosterone levels appeared to
      contribute to more general processes engaged during task performance, for example
      higher levels of visual persistence. It is possible that variability in the
      relative contribution of such hormone sensitive cognitive processes to accuracy
      scores as a function of different sample characteristics or assessment methods
      may partially account for the inconsistent findings of previous research on
      hormonal factors in mental rotation ability.

PMID- 17509597
TI  - The relationship between emotional intelligence, occupational stress and health
      in nurses: a questionnaire survey.
AB  - BACKGROUND: Nurses suffer from stress and health problems owing to the
      characteristics of their work and their contact with patients and death. Since
      emotions can have an effect on work outcomes, emotional intelligence (EI) may
      explain the individual differences in dealing with work stress. OBJECTIVES: This
      study investigated the interrelationships among EI, work stress and health. We
      also examined the impact of socio-demographic variables (e.g. age, gender, length
      of service,...) on stress and nurses' health. DESIGN: A questionnaire survey
      (anonymous) has been carried out to detect these interrelationships. SETTING: A
      general public hospital in Spain PARTICIPANTS: One hundred and eighty nurses.
      METHODS: Data was gathered on demographic information and work, stress, health
      and EI. Beyond descriptive statistics, analyses of variance, mean differences and
      regression analyses were computed. RESULTS: Findings show a differential effect
      of the EI components in stress and health. As far as stress is concerned, the
      results show that the nurses who score high in clarity and emotional repair
      report less stress, whereas those with high scores in attention to emotions
      experience greater levels of stress. Furthermore, we find a positive relationship
      between age, length of service and stress, with younger nurses and those with a
      shorter length of service experiencing less stress. However, EI and health are
      not related to age or to length of service. Also, we find that married nurses
      report better general health. CONCLUSIONS: EI is shown for nurses as a protective
      factor against stress and a facilitative factor for health (especially the
      Clarity and Repair dimensions). These comments could be especially important in
      training future professionals in these abilities.

PMID- 17509598
TI  - Considerations that affect optimised simulation in a running jump for height.
AB  - This study used a computer simulation model to investigate various considerations
      that affect optimum peak height in a running jump. A planar eight-segment
      computer simulation model with extensor and flexor torque generators at five
      joints was formulated and customised to an elite male high jumper. A simulation
      was matched to a recorded high jumping performance by varying the activation
      profiles of each of the torque generators giving a simulated peak height of 1.99m
      compared to the recorded performance of 2.01 m. In order to maximise the peak
      height reached by the mass centre in the flight phase, the activation profiles
      were varied, keeping the same initial conditions as in the matching simulation.
      Optimisations were carried out without any constraints, with constraints on the
      angular momentum at take-off, with further constraints on joint angles, and with
      additional requirements of robustness to perturbations of activation timings. A
      peak height of 2.37 m was achieved in the optimisation without constraints.
      Introducing the three constraints in turn resulted in peak heights of 2.21, 2.14
      and 1.99m. With all three types of constraints included, the peak height was
      similar to that achieved in the recorded performance. It is concluded that such
      considerations have a substantial influence on optimum technique and must be
      included in studies using optimised simulations.

PMID- 17509599
TI  - Counterions in layer-by-layer films--influence of the drying process.
AB  - The amount of counterions, measured by means of X-ray photoelectron spectroscopy
      (XPS), in layer-by-layer (LbL) films of poly(allylamine hydrochloride) (PAH) and
      poly(styrene sulfonate) (PSS), prepared from solutions with various NaCl
      concentrations, is shown to be greatly influenced by the film drying process: a
      smaller amount of counterions is observed in films dried after adsorption of each
      layer, when compared with films that were never dried during the film
      preparation. This is attributed to the formation of NaCl nanocrystals during the
      drying process which dissolve when the film is again immersed in the next
      polyelectrolyte solution. The presence of bonded water molecules was confirmed in
      wet films indicating that the counterions near the ionic groups are immersed in a
      water network. The number of counterions is dependent on the amount of salt in
      polyelectrolyte solutions in such a way that for a concentration of 0.2 M the
      relative amount of counterions attains saturation for both dried and wet samples,
      indicating that the process which leads the aggregation of counterions near of
      the ionic groups is not influenced by the drying process. Moreover, it is proven
      for wet samples that the increase in salt concentration leads to a decrease in
      the number of PAH ionized groups as predicted by the Muthukumar theory [J. Chem.
      Phys. 120 (2004) 9343] accounting for the counterion condensation on flexible
      polyelectrolytes.

PMID- 17509600
TI  - Efficient multicyclic sorption and desorption of lead ions on facilely prepared
      poly(m-phenylenediamine) particles with extremely strong chemoresistance.
AB  - Nitric acid, hydrochloric acid and EDTA were carefully chosen as desorbent to
      systematically evaluate the adsorption/desorption performance of the Pb(2+)
      adsorbing fine microparticles of poly(m-phenylenediamine). The
      sorption/desorption efficiency was maximized by optimizing desorption condition
      including the desorbent concentration, contact time, and desorption mode. The
      variation of the solution pH with Pb(2+) desorption was recorded to speculate the
      desorption mechanism. The practical reusability of the microparticles was
      elaborated through the sorption-desorption cycle experiments in an optimum
      condition. It was found that the desorption was very rapid with an equilibrium
      time of several minutes. A strong dependence of the desorbability on the species
      and concentration of the desorbents was observed. When 20 mM EDTA was chosen as
      the desorbent, the highest desorptivity was up to 94.2% that was much higher than
      those using nitric and hydrochloric acids. A successive sorption-desorption study
      employing nitric acid indicated that the microparticles could be simply
      regenerated and reutilized for more than 5 cycles together with Pb(2+) re
      adsorption efficiency of about 50% and accumulative Pb(2+) adsorption capacity of
      up to 720.4 mg L(-1). Facilely prepared, extremely chemoresistant and cost
      effective PmPD microparticles would be potentially used for multicyclic sorption
      of lead ions from aqueous solution.

PMID- 17509601
TI  - Competitive adsorption of sodium dodecyl sulfate and polyethylene oxide at the
      air/water interface.
AB  - The interfacial and bulk behavior of the aqueous solutions of sodium dodecyl
      sulfate (SDS) and polyethylene oxide (PEO) was investigated by surface tension
      measurements in the presence of excess NaBr. The Gibbs analysis demonstrated that
      the surfactant nearly completely displaces the polymer from the surface even
      below the cac. Furthermore, the adsorbed amount of SDS revealed universal
      features in the presence of PEO above M(PEO)=8x10(3), i.e. it was found to be
      independent of the polymer molar mass. The results were also compared with
      previous neutron reflection measurements on PEO/SDS system without added salt.
      This comparison revealed that the extent of surfactant adsorption as well as the
      displacement of the polymer is more pronounced at high ionic strength. This
      finding might be attributable to the increased adsorption driving force of SDS in
      0.1 M NaBr. Above the cac the criteria of the precise determination of surfactant
      binding isotherms from surface tension measurements were investigated. It was
      shown that the usual formula used for the calculation of the bound amount of
      surfactant from surface tension can only be used at high ionic strength. Finally,
      it was suggested that a sufficient test for the plausibility of the calculated
      binding isotherms might be their independence on the polymer concentration in the
      whole surfactant concentration range and not only at the cmc as the earlier
      studies claimed.

PMID- 17509602
TI  - Removal of 2,4-dichlorophenol from aqueous solution by static-air-activated
      carbon fibers.
AB  - Static-air-activated carbon fibers (ACFs) with lotus-root-like axially porous
      structure were used to adsorb 2,4-dichlorophenol (2,4-DCP) from aqueous solution.
      The adsorption isotherm was evaluated in the pH range 3.0-11.0. Results indicated
      that both Langmuir and Redlich-Peterson adsorption isotherms were appropriate for
      describing the adsorption characteristics of 2,4-DCP at various pH values and
      that lower pH values were favorable for adsorption. The adsorption of 2,4-DCP was
      controlled by the synergetic effects of pi-pi interaction and electrostatic
      attraction, and the former was dominant. Breakthrough curve results showed that
      the 2,4-DCP removal efficiency increased with an increase in the empty-bed
      contact time (EBCT). An EBCT of 0.660 min was sufficient for the adsorption of
      2,4-DCP onto ACF, indicating a high adsorption rate. Desorption experiment
      results revealed that the ACF saturated with 2,4-DCP could be regenerated
      effectively by a 0.001 M NaOH solution.

PMID- 17509603
TI  - Electrophoresis of spheres with uniform zeta potential in a gel modeled as an
      effective medium.
AB  - The effective medium model [H.C. Brinkman, Appl. Sci. Res. A 1 (1947) 27] is used
      to calculate the electrophoretic mobility of spheres in a gel with uniform zeta
      potential on their surface. In the absence of a gel support medium or ion
      relaxation (the distortion of the ion atmosphere from equilibrium due to the
      presence of an external flow or electric field), our results reduce to those of
      Henry [D.C. Henry, Proc. R. Soc. London Ser. A 133 (1931) 106]. The relaxation
      effect can be ignored for weakly charged particles, or for particles with low
      absolute zeta potential. Using a procedure similar to that employed by O'Brien
      and White [R.W. O'Brien, L.R. White, J. Chem. Soc. Faraday Trans. 2 74 (1978)
      1607], the relaxation effect is accounted for in the present work and results are
      presented over a wide range of particle sizes, gel concentrations, and zeta
      potentials in KCl salt solutions. In the limit of no gel, our results reduce to
      those of earlier investigations. The procedure is then applied to the mobility of
      Au nanoparticles in agarose gels and model results are compared to recent
      experiments [D. Zanchet, C.M. Micheel, W.J. Parak, D. Gerion, S.C. Williams, A.P.
      Alivisatos, J. Phys. Chem. B 106 (2002) 11758; T. Pons, H.T. Uyeda, I.L. Medintz,
      H. Mattoussi, J. Phys. Chem. B 110 (2006) 20308]. Good agreement with experiment
      is found for reasonable choices of the model input parameters.

PMID- 17509604
TI  - Electrokinetic coupling in unsaturated porous media.
AB  - We consider a charged porous material that is saturated by two fluid phases that
      are immiscible and continuous on the scale of a representative elementary volume.
      The wetting phase for the grains is water and the nonwetting phase is assumed to
      be an electrically insulating viscous fluid. We use a volume-averaging approach
      to derive the linear constitutive equations for the electrical current density as
      well as the seepage velocities of the wetting and nonwetting phases on the scale
      of a representative elementary volume. These macroscopic constitutive equations
      are obtained by volume-averaging Ampere's law together with the Nernst-Planck
      equation and the Stokes equations. The material properties entering the
      macroscopic constitutive equations are explicitly described as functions of the
      saturation of the water phase, the electrical formation factor, and parameters
      that describe the capillary pressure function, the relative permeability
      functions, and the variation of electrical conductivity with saturation. New
      equations are derived for the streaming potential and electro-osmosis coupling
      coefficients. A primary drainage and imbibition experiment is simulated
      numerically to demonstrate that the relative streaming potential coupling
      coefficient depends not only on the water saturation, but also on the material
      properties of the sample, as well as the saturation history. We also compare the
      predicted streaming potential coupling coefficients with experimental data from
      four dolomite core samples. Measurements on these samples include electrical
      conductivity, capillary pressure, the streaming potential coupling coefficient at
      various levels of saturation, and the permeability at saturation of the rock
      samples. We found very good agreement between these experimental data and the
      model predictions.

PMID- 17509605
TI  - Synthesis and phosphate uptake behavior of Zr4+ incorporated MgAl-layered double
      hydroxides.
AB  - We synthesized Zr(4+) incorporated MgAl-layered double hydroxides, Mg(AlZr)
      LDH(A) (where A denotes a counteranion in the interlayer space and is expressed
      as CO(3) for carbonate and Cl for chloride ions), with different molar ratios of
      Mg/(Al+Zr). Then we characterized their uptake behavior toward phosphate ions.
      CO(3)-type tertiary LDH materials synthesized at room temperature show low
      crystallinity, whereas the highly crystalline Cl-type tertiary LDH,
      [Mg(0.68)Al(0.17)Zr(0.14)(OH)(2)][Cl(0.26)(CO(3))(0.04)1.24H(2)O], was
      synthesized for the first time using a hydrothermal treatment at 120 degrees C.
      The distribution coefficients (K(d)) of oxo-anions were measured with a mixed
      solution containing trace amounts of the anions. The selectivity sequences were
      Cl(-), NO(-)(3)<SO(2-)(4)<<HPO(2-)(4) for CO(3)-type materials and SO(2
      )(4)<HPO(2-)(4)<NO(-)(3) for the crystalline Cl-type material. The uptake of
      phosphate ions from model wastewater (2.0 mg-P/dm(3)) and phosphate-enriched
      natural seawater (0.33 mg-P/dm(3)) was investigated in detail. The CO(3)-type
      materials have higher phosphate uptakes than the Cl-type materials. The maximum
      phosphate uptake of the CO(3)-type material with a molar ratio of Mg/(Al+Zr) of 3
      is 30 mg-P/g at pH 8.7 with the wastewater, and 16 mg-P/g at pH 8.1 with the
      seawater, in contrast to the case of the usual binary MgAl-LDH(CO(3)): 10 mg-P/g
      with the wastewater and less than 1 mg-P/g with the seawater. The large uptake
      and high selectivity of the CO(3)-type tertiary LDH materials is well explained
      by complex formation of phosphate ions directly with Zr(IV) centers in the
      layers.

PMID- 17509606
TI  - Structural and shear characteristics of adsorbed sodium caseinate and
      monoglyceride mixed monolayers at the air-water interface.
AB  - The structural and shear characteristics of mixed monolayers formed by an
      adsorbed Na-caseinate film and a spread monoglyceride (monopalmitin or monoolein)
      on the previously adsorbed protein film have been analyzed. Measurements of the
      surface pressure (pi)-area (A) isotherm and surface shear viscosity (eta(s)) were
      obtained at 20 degrees C and at pH 7 in a modified Wilhelmy-type film balance.
      The structural and shear characteristics of the mixed films depend on the surface
      pressure and on the composition of the mixed film. At surface pressures lower
      than the equilibrium surface pressure of Na-caseinate (at pi<pi(e)(CS)), both Na
      caseinate and monoglyceride coexist at the interface, with a structural
      polymorphism or a liquid expanded structure due to the presence of monopalmitin
      or monoolein in the mixture, respectively. At higher surface pressures, collapsed
      Na-caseinate residues may be displaced from the interface by monoglyceride
      molecules. For a Na-caseinate-monopalmitin mixed film the eta(s) value varies
      greatly with the surface pressure (or surface density) of the mixed monolayer at
      the interface. In general, the greater the surface pressure, the greater are the
      values of eta(s). However, the values of eta(s) for a Na-caseinate-monoolein
      mixed monolayer are very low and practically do not depend on the surface
      pressure. The collapsed Na-caseinate residues displaced from the interface by
      monoglyceride molecules at pi>pi(e)(CS) have important repercussions on the shear
      characteristics of the mixed films.

PMID- 17509607
TI  - Synthesis and micellar properties of surface-active ionic liquids: 1-alkyl-3
      methylimidazolium chlorides.
AB  - A series of surface-active ionic liquids, RMeImCl, has been synthesized by the
      reaction of purified 1-methylimidazole and 1-chloroalkanes, RCl,
      R=C(10),C(12),C(14), and C(16), respectively. Adsorption and aggregation of these
      surfactants in water have been studied by surface tension measurement.
      Additionally, solution conductivity, electromotive force, fluorescence quenching
      of micelle-solubilized pyrene, and static light scattering have been employed to
      investigate micelle formation. The following changes resulted from an increase in
      the length of R: an increase of micelle aggregation number; a decrease of:
      minimum area/surfactant molecule at solution/air interface; critical micelle
      concentration, and degree of counter-ion dissociation. Theoretically-calculated
      aggregation numbers and those based on quenching of pyrene are in good agreement.
      Gibbs free energies of adsorption at solution/air interface, DeltaG(ads)(0), and
      micelle formation in water, DeltaG(mic)(0), were calculated, and compared to
      those of three surfactant series, alkylpyridinium chlorides, RPyCl,
      alkylbenzyldimethylammonium chlorides, RBzMe(2)Cl, and benzyl(3
      acylaminoethyl)dimethylammonium chlorides, R(')AEtBzMe(2)Cl, respectively.
      Contributions to the above-mentioned Gibbs free energies from surfactant
      methylene groups (in the hydrophobic tail) and the head-group were calculated.
      For RMeImCl, the former energy is similar to that of other cationic surfactants.
      The corresponding free energy contribution of the head-group to DeltaG(mic)(0)
      showed the following order: RPyCl approximately
      RBzMe(2)Cl>RMeImCl>R(')AEtBzMe(2)Cl. The head-groups of the first two surfactant
      series are more hydrophobic than the imidazolium ring of RMeImCl, this should
      favor their aggregation. Micellization of RMeImCl, however, is driven by a
      relatively strong hydrogen-bonding between the chloride ion and the hydrogens in
      the imidazolium ring, in particular the relatively acidic H2. This interaction
      more than compensates for the relative hydrophilic character of the diazolium
      ring. As indicated by the corresponding DeltaG(mic)(0), micellization of
      R(')AEtBzMe(2)Cl is more favorable than that of RMeImCl because the CONH group of
      the former surfactant series forms hydrogen bonds to both the counter-ion and the
      neighboring molecules in the micelle.

PMID- 17509608
TI  - Brownian dynamics simulations of copolymer-stabilized nanoparticles in the
      presence of an oil-water interface.
AB  - We describe predictions of properties of copolymer-stabilized nanoparticles in
      the presence of an oil-water interface based on Brownian dynamics simulations.
      These simulations provide information regarding the equilibrium and diffusion
      properties of the stabilized particles. The hydrophilic part of the copolymer is
      modeled as a polyelectrolyte and is described at the Debye-Huckel level. Both
      block and random copolymers are considered. The surface area of particles at the
      fluid interface and the diffusion properties of the particles give some guidance
      into the copolymer architectures that may be most useful for stabilizing
      nanoparticles at fluid interfaces. We find based on our results that a
      conservative recommendation to enhance transportability in a water phase and
      attachment to an oil-water interface would be to design nanoparticles with a
      random copolymer attached to them.

PMID- 17509609
TI  - Examining the effects of multiple sclerosis on speech production: does phonetic
      structure matter?
AB  - The second formant (F2) is well-known to be important to intelligibility (e.g.
      [Delattre, P., Liberman, A., & Cooper, F. (1955). Acoustic loci and transitional
      cues for consonants. Journal of the Acoustical Society of America, 27, 769-774])
      and is affected by a variety of dysarthrias [Weismer, G., & Martin, R. (1992).
      Acoustic and perceptual approaches to the study of intelligibility. In R. Kent
      (Ed.), Intelligibility in speech disorders (pp. 67-118). Amsterdam: John
      Benjamins Publishing Company]. This study tests two related hypotheses: (1)
      dysarthria associated with Multiple Sclerosis (MS) has a greater effect on the
      ability to produce extreme F2 movement than on typical F2 movement and (2)
      phonetic stimuli associated with large and/or rapid F2 movement in healthy
      speakers precipitate larger differences between healthy and dysarthric speech
      than do stimuli associated with small and/or slow F2 movement. Twelve
      participants with MS and 16 healthy controls read aloud the Grandfather Passage.
      F2 slopes were calculated from the F2 tracings (i.e. change in Hz over a 20ms
      lag). For each sentence, the following measures of F2 movement were calculated:
      F2 range (maximum F2-minimum F2), median slope, and 95%ile slope. The mean and
      the maximum observation for each participant were respectively used as measures
      of typical and extreme productions. A repeated-measures MANOVA detected
      significantly larger group differences in the slopes of maximum productions than
      for mean production. Also, group differences in F2 slope were greater in phonetic
      stimuli associated with the largest F2 slopes in healthy speech than in phonetic
      stimuli associated with more shallow slopes. No group differences in F2 range
      were detected. Results indicate dysarthria affects the production of extremely
      rapid changes in F2 and that some phonetic structures are more useful than others
      for detecting these impairments. It is concluded that comparison of speakers'
      best-productions (e.g. maximum F2 slope) yield more useful estimates of the
      effects of mild to moderate dysarthria on F2 slopes than do typical productions.
      LEARNING OUTCOMES: The reader will be able to: (1) describe two approaches to
      measuring typical and extreme acoustic variability that can be applied to
      connected speech, (2) discuss evidence that MS affects extremely rapid changes in
      F2.

PMID- 17509610
TI  - Mating behavior of the hematophagous bug Triatoma infestans: role of Brindley's
      and metasternal glands.
AB  - We investigated if Brindley's and metasternal glands are involved in the sexual
      behavior of Triatoma infestans. In laboratory assays, we analyzed the effect of
      selective occlusion of Brindley's and metasternal glands of the female
      (separately and together) on the behavior of males. Control assays without
      occlusion of glands were also performed. We quantitatively tested if such glands
      affect mating occurrence, the copulatory attempts of males, and the aggregation
      of males around a mating couple. The number of mating attempts by males did not
      differ between treatments, demonstrating that likelihood of males mating did not
      depend on which gland is occluded in the female. In the absence of any occlusion,
      T. infestans mated and males aggregated. The proportion of copulations and
      aggregation behavior of males did not differ between treatments when female's
      Brindley's glands were occluded. However, when metasternal glands were occluded,
      the proportion of mating couples decreased and males did not aggregate. We
      demonstrated that the metasternal glands of the female are involved in the sexual
      behavior of T. infestans, while Brindley's glands seem to have no effect on
      mating behavior. Copulation and aggregation behavior of males likely result from
      the eventual release of volatiles from the female's metasternal glands.

PMID- 17509611
TI  - STAT3 mediates bone marrow mesenchymal stem cell VEGF production.
AB  - The mechanisms by which mesenchymal stem cells (MSCs) may protect native tissue
      are incompletely understood. Understanding the mechanisms by which these cells
      release factors such as vascular endothelial growth factor (VEGF), may lead to
      enhanced protection. We hypothesized that stress, in the form of hypoxia or TNF,
      activates MSCs to release VEGF by STAT3 and p38 MAPK dependent mechanisms. Mouse
      MSCs from wild type (WT) and STAT3 knockout mice (STAT3KO) were harvested and
      purified by a single-step method using adhesion. The release of VEGF was analyzed
      by using MSC conditioned media under hypoxia or TNF stimulation with or without
      p38 MAPK inhibition. Activation of STAT3 and p38 MAPK was determined by analysis
      of cell lysates. MSCs released VEGF under normoxia, which was associated with
      constitutive STAT3 activity. STAT3 deficiency resulted in decreased MSC
      production of VEGF. In response to hypoxia or TNF, MSCs produced more VEGF, which
      was correlated with hypoxia or TNF activated p38 MAPK and STAT3. The p38 MAPK
      inhibitor significantly decreased hypoxia-induced or TNF-stimulated VEGF
      production in WT. Additionally, STAT3 ablation neutralized hypoxia-induced MSC
      release of VEGF. No effect of p38 MAPK inhibitor alone was observed on MSC
      release of VEGF in WT. However, inhibition of p38 MAPK blocked release of VEGF in
      STAT3KO MSCs. MSCs are a potent source of VEGF, the production of which is
      mediated by STAT3 under normoxia partly; however, following hypoxia or TNF
      exposure, MSC release of VEGF is mediated by both STAT3 and p38 MAPK.

PMID- 17509612
TI  - Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic
      cardiomyopathy in humans.
AB  - Junctophilin-2 (JPH2) is a cardiac specific member of the junctophilins, a newly
      characterized family of junctional membrane complex proteins important in
      physically approximating the plasmalemmal L-type calcium channel and the
      sarcoplasmic reticulum ryanodine receptor for calcium-induced calcium release.
      JPH2 knockout mice showed disrupted calcium transients, altered junctional
      membrane complex formation, cardiomyopathy, and embryonic lethality. Furthermore,
      JPH2 gene expression is down-regulated in murine cardiomyopathy models. To this
      end, we explored JPH2 as a novel candidate gene for the pathogenesis of
      hypertrophic cardiomyopathy (HCM) in humans. Using polymerase chain reaction,
      denaturing high performance liquid chromatography, and direct DNA sequencing,
      comprehensive open reading frame/splice site mutational analysis of JPH2 was
      performed on DNA obtained from 388 unrelated patients with HCM. HCM-associated
      JPH2 mutations were engineered and functionally characterized using
      immunocytochemistry, cell morphometry measurements, and live cell confocal
      calcium imaging. Three novel HCM-susceptibility mutations: S101R, Y141H and
      S165F, which localize to key functional domains, were discovered in 3/388
      unrelated patients with HCM and were absent in 1000 ethnic-matched reference
      alleles. Functionally, each human mutation caused (i) protein reorganization of
      junctophilin-2, (ii) perturbations in intracellular calcium signaling, and (iii)
      marked cardiomyocyte hyperplasia. The molecular and functional evidence
      implicates defective junctophilin-2 and disrupted calcium signaling as a novel
      pathogenic mechanism for HCM and establishes HCM as the first human disease
      associated with genetic defects in JPH2. Whether susceptibility for other
      cardiomyopathies, such as dilated cardiomyopathy, can be conferred by mutations
      in JPH2 warrants investigation.

PMID- 17509613
TI  - Amino acids in the second transmembrane helix of the Lhca4 subunit are important
      for formation of stable heterodimeric light-harvesting complex LHCI-730.
AB  - Photosynthetic light-harvesting complexes (LHCs) are assembled from apoproteins
      (Lhc proteins) and non-covalently attached pigments. Despite a considerable amino
      acid sequence identity, these proteins differ in their oligomerization behavior.
      To identify the amino acid residues determining the heterodimerization of Lhca1
      and Lhca4 to form LHCI-730, we mutated the poorly conserved second transmembrane
      helix of the two subunits. Mutated genes were expressed in Escherichia coli and
      the resultant proteins were refolded in vitro and subsequently analyzed by gel
      electrophoresis. Replacement of the entire second helix in Lhca4 by the one of
      Lhca3 abolished heterodimerization, whereas it had no effect in Lhca1. Individual
      replacement of three amino acid clusters in Lhca4 that deviate from the
      corresponding sequence of Lhca3, demonstrated their contribution to Lhca1-Lhca4
      dimerization. Further dissection by mutation of individual amino acid residues in
      Lhca4 showed the importance of a serine, phenylalanine, and histidine (S88, F95,
      H99) for LHCI-730 assembly. Alignment of consensus sequences of the Lhc proteins
      demonstrated that these amino acids are predominantly unique in Lhca4 at the
      relevant positions. Construction of a homology model based on the high-resolution
      structure of LHCII and superimposing these models onto the photosystem I
      structure suggested an orientation of S88, F95, and H99 toward the third
      transmembrane helix of Lhca1. Since some of the amino acids are too far apart
      from their nearest neighbors in Lhca1 for a direct interaction, different modes
      of interaction are discussed. Finally, by quantifying chlorophylls bound to
      monomeric LHC obtained with the H99 mutant, we identified this amino acid as a
      further chlorophyll binding site.

PMID- 17509614
TI  - The transcriptional repression activity of KyoT2 on the Notch/RBP-J pathway is
      regulated by PIAS1-catalyzed SUMOylation.
AB  - The LIM domain protein KyoT2 negatively regulates the Notch signaling pathway
      through interaction with RBP-J, the core element of the Notch signaling pathway
      in the nucleus. Here we show that PIAS1 (the protein inhibitor of activated
      STAT1) interacts with KyoT2 directly and attenuates KyoT2-mediated
      transcriptional repression. We demonstrate that KyoT2 is modified by SUMOylation
      at two lysine residues, K144 and K171. SUMOylation of the transfected KyoT2 is
      enhanced by PIAS1 but not hPc2, another KyoT2-interacting protein with SUMO E3
      ligase activity, and is repressed by a PIAS1 mutant that is deficient of E3
      ligase activity. Using mutants disrupting either or both of the SUMO sites, we
      show that SUMOylation of KyoT2 does not influence its expression, intracellular
      localization, or interaction with known partners. However, disruption of the K171
      SUMOylation site does reinforce the transcriptional repression activity of KyoT2,
      suggesting that SUMOylation of this site counters the repression activity of
      KyoT2. Finally, we show that PIAS1 fails to attenuate the repression activity of
      the K171R mutant of KyoT2, suggesting that PIAS1 may potentially antagonize the
      transcriptional repression activity of KyoT2 through catalyzing its SUMOylation
      at K171. These results suggest that KyoT2 is a substrate of SUMO modification
      catalyzed by PIAS1, and that SUMOylation may modulate the transcriptional
      repression effect of KyoT2 on the Notch/RBP-J signaling pathway.

PMID- 17509615
TI  - A case of dystonia with onset during pregnancy.
AB  - We report the clinical and therapeutic approach of a case of 'dystonia
      gravidarum'. The patient came to our observation with neck and bilateral feet
      dystonia, appearing after the onset of pregnancy. She was treated with
      clonazepam, 0.5 mg three times a day, during the pregnancy. After delivery of a
      healthy full-term child by caesarean section, she was completely able to turn her
      neck to either side.

PMID- 17509616
TI  - Prediction of protein coding regions by the 3-base periodicity analysis of a DNA
      sequence.
AB  - With the exponential growth of genomic sequences, there is an increasing demand
      to accurately identify protein coding regions (exons) from genomic sequences.
      Despite many progresses being made in the identification of protein coding
      regions by computational methods during the last two decades, the performances
      and efficiencies of the prediction methods still need to be improved. In
      addition, it is indispensable to develop different prediction methods since
      combining different methods may greatly improve the prediction accuracy. A new
      method to predict protein coding regions is developed in this paper based on the
      fact that most of exon sequences have a 3-base periodicity, while intron
      sequences do not have this unique feature. The method computes the 3-base
      periodicity and the background noise of the stepwise DNA segments of the target
      DNA sequences using nucleotide distributions in the three codon positions of the
      DNA sequences. Exon and intron sequences can be identified from trends of the
      ratio of the 3-base periodicity to the background noise in the DNA sequences.
      Case studies on genes from different organisms show that this method is an
      effective approach for exon prediction.

PMID- 17509617
TI  - The relevance of xylem network structure for plant hydraulic efficiency and
      safety.
AB  - The xylem is one of the two long distance transport tissues in plants, providing
      a low resistance pathway for water movement from roots to leaves. Its properties
      determine how much water can be transported and transpired and, at the same time,
      the plant's vulnerability to transport dysfunctions (the formation and
      propagation of emboli) associated to important stress factors, such as droughts
      and frost. Both maximum transport efficiency and safety against embolism have
      classically been attributed to the properties of individual conduits or of the
      pit membrane connecting them. But this approach overlooks the fact that the
      conduits of the xylem constitute a network. The topology of this network is
      likely to affect its overall transport properties, as well as the propagation of
      embolism through the xylem, since, according to the air-seeding hypothesis,
      drought-induced embolism propagates as a contact process (i.e., between
      neighbouring conduits). Here we present a model of the xylem that takes into
      account its system-level properties, including the connectivity of the xylem
      network. With the tools of graph theory and assuming steady state and Darcy's
      flow we calculated the hydraulic conductivity of idealized wood segments at
      different water potentials. A Monte Carlo approach was adopted, varying the
      anatomical and topological properties of the segments within biologically
      reasonable ranges, based on data available from the literature. Our results
      showed that maximum hydraulic conductivity and vulnerability to embolism increase
      with the connectivity of the xylem network. This can be explained by the fact
      that connectivity determines the fraction of all the potential paths or conduits
      actually available for water transport and spread of embolism. It is concluded
      that the xylem can no longer be interpreted as the mere sum of its conduits,
      because the spatial arrangement of those conduits in the xylem network influences
      the main functional properties of this tissue. This brings new arguments into the
      long-standing discussion on the efficiency vs. safety trade-off in the plants'
      xylem.

PMID- 17509618
TI  - Age-related changes in the gastrointestinal tract: a functional and
      immunohistochemical study in guinea-pig ileum.
AB  - It is known that there is an age-related increase in gastrointestinal diseases.
      However, there is a lack of studies dealing with the correlation between age
      related changes in function and intrinsic innervation in the gastrointestinal
      tract. The purpose of this work was to study this subject in the guinea pig
      ileum, whose functional and structural features are well known in the young age.
      Ileal longitudinal muscle -- myenteric plexus (LMMP) preparations were obtained
      from 3-to 24-month-old guinea pigs. Both functional and immunohistochemical
      techniques were applied. The force of the contraction elicited by excitatory
      stimuli (electrical stimulation, acetylcholine, substance P, and opioid
      withdrawal) increased in parallel with an age-dependent reduction in the density
      of excitatory motor neurones to the longitudinal muscle, whereas other
      subpopulations of neurones, including inhibitory motor neurones, decreased much
      more slowly. Although the increase in responsiveness could be related to the
      age/weight-related increment in muscle bulk, some compensatory modifications to
      the lowered density of excitatory neurones could also be involved. On the other
      hand, the acute inhibitory response to morphine remained unaltered in old
      animals, whilst in vitro tolerance was lower. These results suggest that although
      age-dependent neuronal loss does not cause dramatic changes in intestinal
      motility, it is a factor that could contribute to disturbing normal
      responsiveness and, perhaps, underlie the higher frequency of gastrointestinal
      diseases encountered in the elderly.

PMID- 17509620
TI  - Polycyclic aromatic hydrocarbons (PAHs), organic matter quality and meiofauna in
      Galician sandy beaches, 6 months after the Prestige oil-spill.

PMID- 17509619
TI  - Proteomic approach to study the effects of various oxidatively modified low
      density lipoprotein on regulation of protein expression in human umbilical vein
      endothelial cell.
AB  - Circulating low-density lipoprotein (LDL) isolated by our laboratory, a new form
      of modified LDL and designated as L5, has been reported to be cytotoxic by
      inducing apoptosis of vascular endothelial cells in vitro. The objective of this
      study was to compare the biological functions of three different forms of
      oxidatively modified LDL on human umbilical vein endothelial cells (HUVEC) by
      proteomic approaches. HUVEC were incubated with serum-free medium, native LDL (N
      LDL), L5 isolated from familial hypercholesterolemic subjects (FH-L5), copper
      oxidized LDL (Cu-ox-LDL), and atheroma-derived LDL (a-LDL) at 37 degrees C for 24
      h. We found that HUVEC incubated with FH-L5 expressed approximately 3 fold higher
      concentration of MCP-1 than did cells subject to other treatments. All modified
      LDL significantly suppressed ATP synthase, Grp58, Grp78, and Prdx3. However, the
      expression of hnRNP C1/C2 was significantly enhanced by FH-L5 and a-LDL;
      glutathione transferase was significantly enhanced only by FH-L5. A concordant
      pattern of protein expression was observed between immunoblotting and 2D
      electrophoresis. Different forms of oxidatively modified LDL regulated HUVEC
      protein expression in different patterns, suggesting different roles for
      different oxLDL forms in inducing atherogenesis.

PMID- 17509621
TI  - Assessment of persistent organochlorine residues in sediments of Hadramout
      coastal area, Gulf of Aden, Yemen.

PMID- 17509622
TI  - Variability in invasion risk for ballast water exchange on the Scotian Shelf of
      eastern Canada.
AB  - A semi-quantitative risk assessment model for dispersion of ballast water
      organisms in shelf seas is applied to the Scotian Shelf region of eastern Canada.
      The ballast water exchange process is simulated as the dispersion of tracer
      released into the surface layer of an ocean circulation model of the region.
      Circulation model variability is driven by wind stress from a cyclical year of
      forcing representing climatological storminess. Dispersion metrics related to
      invasion risk are developed and incorporated into a risk equation that computes
      the relative overall risk of invasion for ballast water exchange segments along
      vessel tracks crossing the shelf. Three hundred and sixty dispersion simulations
      are done for each segment of each of six tracks. Because the flow fields
      represent climatological variability in shelf circulation, the application of the
      risk assessment model captures the expected variability in invasion risk. Model
      results indicate that more than an order of magnitude variation in risk can exist
      along a given vessel track, and that tracks with offshelf segments provide a
      lower risk option compared to onshelf tracks. The model provides quantitative
      guidance to regulators regarding what is an acceptable trip diversion and can aid
      in numerous other management decisions.

PMID- 17509623
TI  - Cytotoxicity and mutagenicity of dibenzo[a,l]pyrene and (+/-)-dibenzo[a,l]pyrene
      11,12-dihydrodiol in V79MZ cells co-expressing either hCYP1A1 or hCYP1B1 together
      with human glutathione-S-transferase A1.
AB  - We have used V79MZ hamster lung fibroblasts stably transfected with human
      cytochrome P450-1A1 (hCYP1A1; cell line designated V79MZh1A1) or P450-1B1
      (hCYP1B1; cell line designated V79MZh1B1) alone, or in combination with human
      glutathione-S-transferase (GST) alpha-1 (hGSTA1), in order to examine GST
      protection against cytotoxicity and mutagenicity of dibenzo[a,l]pyrene (DBP) and
      the intermediate dihydrodiol metabolite (+/-)-DBP-11,12-dihydrodiol (DBPD). At
      comparable expression levels of hCYP1A1 and hCYP1B1, both DBP and DBPD were more
      cytotoxic in V79MZ1A1 (IC(50)=2.7 and 0.7nM, respectively) than in V79MZh1B1
      (IC(50)=6.0 and 4.8nM, respectively). In contrast, both DBP and DBPD were two- to
      four-fold more mutagenic in V79MZh1B1 than in V79MZ1A1. Co-expression of hGSTA1
      with hCYP1A1 decreased DBP cytotoxicity two-fold compared to V79MZh1A1 with
      hCYP1A1 alone, and provided a small, yet still statistically significant, 1.3
      fold protection against DBPD. Protection against mutagenicity of these compounds
      was comparable to that for cytotoxicity in cells expressing hCYP1A1. In V79MZh1B1
      cells, co-expression of hGSTA1 conferred up to five-fold protection against DBP
      cytotoxicity, and up to nine-fold protection against the (+/-)-DBP-dihydrodiol
      cytotoxicity relative to the cells expressing hCYP1B1 alone. Co-expression of
      hGSTA1 also reduced mutagenicity of DBP or its dihydrodiol to a lesser extent
      (1.3-1.8-fold) than the protection against cytotoxicity in cells expressing
      hCYP1B1. These findings demonstrate that the protective efficacy of hGSTA1
      against DBP and DBPD toxicity is variable, depending on the compound or
      metabolite present, the specific cytochrome P450 isozyme expressed, and the
      specific cellular damage endpoint examined.

PMID- 17509624
TI  - Genetic profile of the arylamine N-acetyltransferase 2 coding gene among
      individuals from two different regions of Brazil.
AB  - Arylamine N-acetyltranferase 2 is the main enzyme responsible for the isoniazid
      metabolization into hepatotoxic intermediates and the degree of hepatotoxicity
      severity has been attributed to genetic variability in the NAT2 gene. The main
      goal of this study was to describe the genetic profile of the NAT2 gene in
      individuals from two different regions of Brazil: Rio de Janeiro and Goias
      States. Therefore, after preparation of DNA samples from 404 individuals,
      genotyping of the coding region of NAT2 was performed by direct PCR sequencing.
      Thirteen previously described SNPs were detected in these Brazilian populations,
      from which seven: 191 G>A; 282 C>T; 341 T>C; 481 C>T; 590 G>A; 803 A>G and 857
      G>A are the most frequent in other populations. The presence of so-called ethnic
      specific SNPs in our population is in accordance with the Brazilians' multiple
      ancestry. Upon allele and genotype analysis, the most frequent NAT2 alleles were
      respectively NAT2*5B (33%), NAT2*6A (26%) and NAT2*4 (20%) being NAT2*5/*5 the
      more prevalent genotype (31.7%). These results clearly demonstrate the
      predominance in the studied Brazilian groups of NAT2 alleles associated with slow
      over the fast and intermediate acetylator genotypes. Additionally, in Rio de
      Janeiro, a significantly higher frequency of intermediate acetylation status was
      found when compared to Goias (42.5% versus 25%) (p=0.05), demonstrating that
      different regions of a country with a population characterized by a multi-ethnic
      ancestry may present a large degree of variability in NAT2 allelic frequencies.
      This finding has implications in the determination of nationwide policies for use
      of appropriate anti-TB drugs.

PMID- 17509625
TI  - Interhemispheric transfer following callosotomy in humans: role of the superior
      colliculus.
AB  - It is now common knowledge that the total surgical section of the corpus callosum
      (CC) and of the other forebrain commissures prevents interhemispheric transfer
      (IT) of a host of mental functions. By contrast, IT of simple sensorimotor
      functions, although severely delayed, is not abolished, and an important question
      concerns the pathways subserving this residual IT. To answer this question we
      assessed visuomotor IT in split-brain patients using the Poffenberger paradigm
      (PP), that is, a behavioral paradigm in which simple reaction time (RT) to visual
      stimuli presented to the hemifield ipsilateral to the responding hand is compared
      to stimuli presented to the contralateral hemifield, a condition requiring an IT.
      We tested the possibility that the residual IT is mediated by the collicular
      commissure interconnecting the two sides of the superior colliculus (SC). To this
      purpose, we used short-wavelength visual stimuli, which in neurophysiological
      studies in non-human primates have been shown to be undetectable by collicular
      neurons. We found that, in both totally and partially callosotomised patients, IT
      was considerably longer with S-cone input than with L-cone input or with
      achromatic stimuli. This was not the case in healthy participants in whom IT was
      not affected by color. These data clearly show that the SC plays an important
      role in IT of sensorimotor information in the absence of the corpus callosum.

PMID- 17509626
TI  - Recognition memory for faces and scenes in amnesia: dissociable roles of medial
      temporal lobe structures.
AB  - The relative contributions of the hippocampus and the perirhinal cortex to
      recognition memory are currently the subject of intense debate. Whereas some
      authors propose that both structures play a similar role in recognition memory,
      others suggest that the hippocampus might mediate recollective and/or associative
      aspects of recognition memory, whereas the perirhinal cortex may mediate item
      memory. Here we investigate an alternative functional demarcation between these
      structures, following reports of stimulus-specific perceptual deficits in
      amnesics with medial temporal lobe (MTL) lesions. Using a novel recognition
      memory test for faces and scenes, participants with broad damage to MTL
      structures, which included the hippocampus and the perirhinal cortex, were
      impaired on both face and scene memory. By contrast, participants with damage
      limited to the hippocampus showed deficits only in memory for scenes. These
      findings imply that although both the hippocampus and surrounding cortex
      contribute to recognition memory, their respective roles can be distinguished
      according to the type of material to be remembered. This interaction between
      lesion site and stimulus category may explain some of the inconsistencies present
      in the literature.

PMID- 17509627
TI  - Speed of lexical decision correlates with diffusion anisotropy in left parietal
      and frontal white matter: evidence from diffusion tensor imaging.
AB  - Speed of visual word recognition is an important variable affecting linguistic
      competence. Although speed of visual word recognition varies widely between
      individuals, the neural basis of reaction time (RT) differences is poorly
      understood. Recently, a magnetic resonance technique called diffusion tensor
      imaging (DTI) has been shown to provide information about white matter (WM)
      microstructure in vivo. Here, we used DTI to explore whether visual word
      recognition RT correlates with regional fractional anisotropy (FA) values in the
      WM of healthy young adults. Participants completed a speeded lexical decision
      task that involved visual input, linguistic processes, and a motor response
      output. Results indicated that lexical decision RT was correlated negatively with
      FA in WM of inferior parietal and frontal language regions rather than in WM of
      visual or motor regions. Voxels within the inferior parietal and frontal
      correlation clusters were composed primarily of DTI-based tracts oriented in the
      anterior-posterior orientation at or near the superior longitudinal fasciculus
      (SLF) and likely including other smaller association fibers. These results
      provide new microstructural evidence demonstrating that speed of lexical decision
      is associated with the degree to which portions of frontal and parietal WM are
      directionally oriented.

PMID- 17509628
TI  - Parallel determination of enzyme activities and in vivo fluxes in Brassica napus
      embryos grown on organic or inorganic nitrogen source.
AB  - After the completion of the genomic sequencing of model organisms, numerous post
      genomic studies, integrating transcriptome and metabolome data, are aimed at
      developing a more complete understanding of cell physiology. Here, we measure in
      vivo metabolic fluxes by steady state labeling, and in parallel, the activity of
      enzymes in central metabolism in cultured developing embryos of Brassica napus.
      Embryos were grown on either the amino acids glutamine and alanine as an organic
      nitrogen source, or on ammonium nitrate as an inorganic nitrogen source. The type
      of nitrogen made available to developing embryos caused substantial differences
      in fluxes associated with the tricarboxylic acid cycle, including flux reversion.
      The changes observed in enzyme activity were not consistent with our estimates of
      metabolic flux. Furthermore, most extractable enzyme activities are in large
      surplus relative to the requirements for the observed in vivo fluxes. The results
      demonstrate that in this model system the metabolic response of central
      metabolism to changes in environmental conditions can be achieved largely without
      regulatory reprogramming of the enzyme machinery.

PMID- 17509629
TI  - Introduction of sense constructs of cinnamate 4-hydroxylase (CYP73A24) in
      transgenic tomato plants shows opposite effects on flux into stem lignin and
      fruit flavonoids.
AB  - Understanding regulation of phenolic metabolism underpins attempts to engineer
      plants for diverse properties such as increased levels of antioxidant flavonoids
      for dietary improvements or reduction of lignin for improvements to fibre
      resources for industrial use. Previous attempts to alter phenolic metabolism at
      the level of the second enzyme of the pathway, cinnamate 4-hydroxylase have
      employed antisense expression of heterologous sequences in tobacco. The present
      study describes the consequences of homologous sense expression of tomato
      CYP73A24 on the lignin content of stems and the flavonoid content of fruits. An
      extensive number of lines were produced and displayed four developmental variants
      besides a normal phenotype. These aberrant phenotypes were classified as dwarf
      plants, plants with distorted (curly) leaves, plants with long internodes and
      plants with thickened waxy leaves. Nevertheless, some of the lines showed the
      desired increase in the level of rutin and naringenin in fruit in a normal
      phenotype background. However this could not be correlated directly to increased
      levels of PAL and C4H expression as other lines showed less accumulation,
      although all lines tested showed increases in leaf chlorogenic acid which is
      typical of Solanaceous plants when engineered in the phenylpropanoid pathway.
      Almost all transgenic lines analysed showed a considerable reduction in stem
      lignin and in the lines that were specifically examined, this was correlated with
      partial sense suppression of C4H. Although not the primary purpose of the study,
      these reductions in lignin were amongst the greatest seen in plants modified for
      lignin by manipulation of structural genes. The lignin showed higher syringyl to
      coniferyl monomeric content contrary to that previously seen in tobacco
      engineered for downregulation of cinnamate 4-hydroxylase. These outcomes are
      consistent with placing CYP73A24 more in the lignin pathway and having a role in
      flux control, while more complex regulatory processes are likely to be involved
      in flavonoid and chlorogenic acid accumulation.

PMID- 17509630
TI  - Crystal structure of chenodeoxycholic acid, ursodeoxycholic acid and their two
      3beta,7alpha- and 3beta,7beta-dihydroxy epimers.
AB  - The crystal structures of chenodeoxycholic acid (CDCA), ursodeoxycholic acid
      (7beta isomer of CDCA) and their other two epimers (3beta,7alpha- and 3beta,7beta
      isomers) have been resolved. The four isomers were recrystallized from p-xylene.
      CDCA crystal is hexagonal P6(5) while the crystals of the other three isomers are
      orthorhombic (P2(1)2(1)2(1) space group). Only the 3beta,7beta isomer forms an
      inclusion complex with the solvent with a 1:1 stoichiometry. In all cases, the
      three hydrogen bond sites (the two hydroxy groups, O3-H and O7-H, and the
      carboxylic acid group of the side chain, O24bO24a-H) simultaneously act as
      hydrogen bond donors and acceptors. By considering that O24a is always donor and
      O24b is always acceptor, the hydrogen bond sequences can be understood on the
      basis of the interaction between the two hydroxy groups. However the comparison
      between the four compounds is complicated by the existence of two molecules in
      the asymmetric unit in the UDCA crystal resulting in that the same hydrogen bond
      site (for instance O3) can be donor towards two different acceptors (either O7 or
      O24b). As in the case of the four isomers of deoxycholic acid (Steroids 2004, 69,
      379), the other three isomers present a donor-->acceptor sequence, which is O7-
      >O3 when O3-H is beta and O3-->O7 when O3-H is alpha. The spatial orientation of
      the carboxylic acid of the side chain is referred to two almost perpendicular
      planes (defined by (1) the carbon atoms C1/C6-C17/C20 and by (2) the methyl
      groups C18-C19 and the two carbon atoms to which they are linked, C10 and C13,
      respectively). Only the side chain of CDCA evidences a positive deviation towards
      the hydrophobic beta side of the molecule.

PMID- 17509631
TI  - The glucocorticoid agonist activities of mifepristone (RU486) and progesterone
      are dependent on glucocorticoid receptor levels but not on EC50 values.
AB  - Mifepristone is an antagonist of the glucocorticoid receptor (GR) that also has
      significant agonist activity in some cell types. We examined the partial agonist
      activity of mifepristone in COS-7 cells transfected with increasing amounts of a
      glucocorticoid receptor expression vector pmGR. As pmGR levels increased, the
      response of the reporter, pMTVCAT to dexamethasone increased, consistent with
      increasing levels of receptor expression; the response to mifepristone also
      increased but at a higher rate, resulting in increasing mifepristone agonist and
      decreasing antagonist activity. In contrast, increasing pMTVCAT levels increased
      CAT activity induced by both dexamethasone and mifepristone, but did not change
      the relative agonist activity of mifepristone. We also examined the relationship
      between agonist activity and receptor level in a series of clones of the E8.2.A3
      cell line expressing various levels of GR. Again, the relative agonist activity
      of mifepristone increased as GR increased. This increase was not due to changes
      in the dose response curves to these two ligands since their EC50 values were
      independent of receptor levels. These results indicate that the degree of
      glucocorticoid agonist activity exhibited by mifepristone is dependent on the
      concentration of GR in the cell. Similar results were obtained with another
      partial agonist of the GR, progesterone, whereas the complete antagonist ZK98.299
      had no agonist activity under any condition. Taken together, these results
      suggest that the phenomenon of receptor concentration-dependence is a property of
      partial GR agonists in general.

PMID- 17509632
TI  - Steroidal isomers with uniform mass spectra of their per-TMS derivatives:
      synthesis of 17-hydroxyandrostan-3-ones, androst-1-, and -4-ene-3,17-diols.
AB  - In human sports doping control analysis most of the steroids are analyzed after
      enzymatic hydrolysis of the glucuronides as per-trimethylsilyl (TMS) derivatives
      applying gas chromatography-mass spectrometry (GC-MS). According to the
      recommendations of the World Anti-Doping Agency the identification of analytes
      should be based on retention time and on mass spectrometric characterization.
      This study shows that the bis-TMS derivatives of 16 specific C19 steroids, namely
      the stereoisomers of 5xi-androst-1-ene-3xi,17xi-diol (8 isomers), androst-4-ene
      3xi,17xi-diol (4 isomers), and 17xi-hydroxy-5xi-androstan-3-one (4 isomers),
      reveal very similar mass spectra. As a rule, when taking the retention times,
      which are provided as Kovac indices for all these isomers, into account, a
      restriction to two or three possible isomers is possible. Reliable identification
      should additionally include a comparison of the retention times of the analytes
      with the reference compounds measured concomitantly. In some cases standard
      addition may be appropriate. Due to the limited availability, the above mentioned
      isomers were synthesized by reduction of the corresponding alpha,beta-unsaturated
      oxo steroids either with K-Selectride or by catalytic hydrogenation (Pd/C as
      catalyst). The products of the reactions were identified by means of nuclear
      magnetic resonance (NMR) characterization and by further reduction to the
      corresponding 5xi-androstane-3xi,17xi-diols and GC-MS comparison with
      commercially available reference standards.

PMID- 17509633
TI  - The ratio of estrogen receptor alpha to estrogen receptor beta in adipose tissue
      is associated with leptin production and obesity.
AB  - The loss of estrogen associated with menopause is suspected to play an important
      regulatory role in changes of fat metabolism and obesity. To evaluate the
      relationship between obesity and the ratio of estrogen receptor subtypes
      (ERalpha/ERbeta) in adipose tissues in pre- and postmenopausal women, we measured
      the anthropometric indices of 31 premenopausal women and 12 postmenopausal women.
      Serum samples, subcutaneous and omental adipose tissues were also obtained from
      study participants. Serum leptin, adiponectin, IL-6, and TNF-alpha levels were
      measured using ELISA methods. Real-time RT-PCR analysis was performed to detect
      and to compare mRNA levels of leptin and estrogen receptor subtypes (ERalpha and
      ERbeta) from adipose tissues. The ratio of abdominal subcutaneous to omental
      adipose tissue for the ER subtypes (Sc-Om ratio of the ER subtypes), i.e.,
      subcutaneous ERalpha/ERbeta over omental ERalpha/ERbeta, showed significant
      correlations with anthropometric indices including BMI (r=0.801, p<0.05) and
      waist circumference (r=0.696, p<0.05) in both pre- and postmenopausal women. The
      Sc-Om ratio of the ER subtypes also had a significant correlation with the serum
      leptin level (r=0.735, p<0.05) as well as the mRNA level of leptin in omental
      adipose tissue (r=0.753, p<0.05). However, there were no significant differences
      between the pre- and postmenopausal groups with regard to the expressed level of
      ER subtypes. In conclusion, our study results showed that the ratio of ERalpha to
      ERbeta in adipose tissue was associated with obesity as well as the serum level
      and production of leptin in omental adipose tissue.

PMID- 17509634
TI  - Hydrocortisone does not affect major platelet receptors in inflammation in vitro.
AB  - HYPOTHESIS: Platelet function is an important factor for the fate of intensive
      care patients. Several factors may influence this function. Recently, it was
      demonstrated that hydrocortisone has immunologic effects in septic shock and
      therefore may affect cell adhesion molecules. The aim of the present study was to
      examine effects of hydrocortisone on platelet receptor expression in healthy
      individuals and septic patients in vitro. METHODS: Citrated blood samples were
      drawn from 10 healthy volunteers and 10 septic patients. Samples were adjusted
      with hydrocortisone to final concentrations of 4.5 microg mL(-1), 9.0 microg mL(
      1) (sepsis-equivalent bolus) and 90 microg mL(-1), respectively. A control group
      received no additional hydrocortisone. Expression of CD62P, CD41, PAC-1 and CD42b
      on the surface of resting or agonist-stimulated platelets was determined by whole
      blood flow cytometry using fluorescence-labeled monoclonal antibodies. RESULTS:
      Hydrocortisone had no significant influence on the expression of CD62P, CD41 and
      PAC-1. After administration of 90 microg mL(-1) hydrocortisone the expression of
      CD42b was decreased compared to controls after activation. Differences between
      volunteers and sepsis patients were found for all receptors after activation.
      CONCLUSIONS: Hydrocortisone mediates immunmodulating effects in therapy of
      patients suffering of septic shock without involvement of specific platelet
      receptors in vitro.

PMID- 17509635
TI  - Drinking water arsenic exposure and blood pressure in healthy women of
      reproductive age in Inner Mongolia, China.
AB  - The extremely high exposure levels evaluated in prior investigations relating
      elevated levels of drinking water arsenic and hypertension prevalence make
      extrapolation to potential vascular effects at lower exposure levels very
      difficult. A cross-sectional study was conducted on 8790 women who had recently
      been pregnant in an area of Inner Mongolia, China known to have a gradient of
      drinking water arsenic exposure. This study observed increased systolic blood
      pressure levels with increasing drinking water arsenic, at lower exposure levels
      than previously reported in the literature. As compared to the referent category
      (below limit of detection to 20 microg of As/L), the overall population mean
      systolic blood pressure rose 1.29 mm Hg (95% CI 0.82, 1.75), 1.28 mm Hg (95% CI
      0.49, 2.07), and 2.22 mm Hg (95% CI 1.46, 2.97) as drinking water arsenic
      concentration increased from 21 to 50, 51 to 100, and >100 microg of As/L,
      respectively. Controlling for age and body weight (n=3260), the population mean
      systolic blood pressure rose 1.88 mm Hg (95% CI 1.03, 2.73), 3.90 mm Hg (95% CI
      2.52, 5.29), and 6.83 mm Hg (95% CI 5.39, 8.27) as drinking water arsenic
      concentration increased, respectively. For diastolic blood pressure effect, while
      statistically significant, was not as pronounced as systolic blood pressure. Mean
      diastolic blood pressure rose 0.78 mm Hg (95% CI 0.39, 1.16), 1.57 mm Hg (95% CI
      0.91, 2.22) and 1.32 mm Hg (95% CI 0.70, 1.95), respectively, for the overall
      population and rose 2.11 mm Hg (95% CI 1.38, 2.84), 2.74 mm Hg (95% CI 1.55,
      3.93), and 3.08 mm Hg (95% CI 1.84, 4.31), respectively, for the adjusted
      population (n=3260) at drinking water arsenic concentrations of 21 to 50, 51 to
      100, and >100 microg of As/L. If our study results are confirmed in other
      populations, the potential burden of cardiovascular disease attributable to
      drinking water arsenic is significant.

PMID- 17509636
TI  - Cyanobacterial toxins present in Microcystis aeruginosa extracts--more than
      microcystins!

PMID- 17509637
TI  - AGS and other tissue culture cells can unknowingly be persistently infected with
      PIV5; a virus that blocks interferon signalling by degrading STAT1.
AB  - Whilst screening various cell lines for their ability to respond to interferon
      (IFN), we noted that in comparison to other tissue culture cells AGS tumour
      cells, which are widely used in biomedical research, had very low levels of
      STAT1. Subsequent analysis showed that the reason for this is that AGS cells are
      persistently infected with parainfluenza virus type 5 (PIV5; formally known as
      SV5), a virus that blocks the interferon (IFN) response by targeting STAT1 for
      proteasome-mediated degradation. Virus protein expression in AGS is altered in
      comparison to the normal pattern of virus protein synthesis observed in acutely
      infected cells, suggesting that the AGS virus is defective. We discuss the
      relevance of these results in terms of the need to screen cell lines for
      persistent virus infections that can alter cellular functions.

PMID- 17509638
TI  - Cone-based vision in the aging mouse.
AB  - People often experience age-related declines in cone-based visual capacities
      despite an absence of apparent visual pathology. Although mice are used as models
      of human visual pathologies associated with aging, little is known about how age
      impacts vision in animals with disease-free retinas since most studies have
      heretofore examined relatively young mice. We examined the effects of age on cone
      based vision by assessing opsin gene transcription, cone densities, the flicker
      electroretinogram (ERG), and behavioral increment thresholds in mice. ERG
      measurements of cone function showed age-related declines in maximum voltage
      (Vmax), while opsin gene transcription, cone density, and increment thresholds
      were unchanged even in extremely old mice. The age-related decline in Vmax seen
      in mice is qualitatively similar to that documented for human subjects. It is
      notable that Vmax, a commonly used index of ERG activity, does not predict
      behavioral performance in the mouse.

PMID- 17509639
TI  - Anaerobic degradation of dimethyl phthalate in wastewater in a UASB reactor.
AB  - Over 99% of dimethyl phthalate (DMP) and 93% of chemical oxygen demand (COD) were
      effectively removed in a continuous upflow anaerobic sludge blanket (UASB)
      reactor from a wastewater containing 600 mg/L DMP at 8h of hydraulic retention
      time (HRT), corresponding to a loading rate of 3g-COD/(Ld). Each gram of sludge,
      expressed as volatile suspended solids (VSS), had a maximum specific methanogenic
      activity (SMA) of 24 mg-CH(4)/(g-VSSd) using DMP as the sole carbon source. The
      sludge yield was estimated as 0.08 g-VSS/g-COD. During anaerobic degradation, DMP
      was de-esterified, first to mono-methyl phthalate (MMP) and then to phthalate,
      before being de-aromatized and subsequently converted to CH(4) and CO(2). The
      maximum specific degradation rates of DMP, MMP and phthalate were 415, 88 and 36
      mg/(g-VSSd), respectively. Analysis based on polymerase chain reaction (PCR) and
      denaturing gradient gel electrophoresis (DGGE) showed a gradual shift of
      microbial population with the increase of DMP loading.

PMID- 17509640
TI  - Congener-specific approach to human PCB concentrations by serum analysis.
AB  - The objective of this study was to evaluate all congeners of polychlorinated
      biphenyls (PCBs) in human serum samples. Concentrations of all PCB congeners in
      the serum of 87 volunteers were determined by high-resolution gas
      chromatography/high-resolution mass spectrometry (HRGC/HRMS). The participants
      consisted of 47 males and 40 females, including 25 men working at municipal solid
      waste incinerators (MSWIs). The mean concentrations of total PCBs and dioxin-like
      PCBs were 242.77ng/g lipid (median: 180.17ng/g lipid) and 18.57ng/g lipid
      (median: 15.34ng/g lipid), respectively. Penta-, hexa-, and heptachlorinated
      biphenyls contributed more than 80% of the total PCBs detected in human serum.
      Congener-specific analysis indicated that PCB153, PCB138, PCB180, PCB187, and
      PCB118 contributed 57.3% of the total PCBs detected in human serum samples. A
      statistical analysis was performed to determine whether there were significant
      correlations between PCB concentrations and specific variables such as age,
      gender, smoking habits, occupation, and body mass index (BMI). However, serum PCB
      concentrations correlated only with age. In addition, we found that total PCBs
      and dioxin-like PCBs highly correlated with PCB153 (correlation coefficient
      r=0.93, p<0.01) and PCB118 (correlation coefficient r=0.98, p<0.01),
      respectively. Thus these two congeners could be satisfactory indicators for total
      PCBs and dioxin-like PCBs in human serum.

PMID- 17509641
TI  - Soil distribution of fipronil and its metabolites originating from a seed-coated
      formulation.
AB  - Seed-coating with the insecticide fipronil has been intensively used in sunflower
      cultivation to control soil pests such as wireworms. A research project was
      undertaken to determine the soil distribution of fipronil and of its main
      phenylpyrazole metabolites. Under agronomic conditions, the quantity of fipronil
      in the seed-coat (437 microg/seed) decreased continuously during the cultivation
      period (3.9 microg day(-1) during the first two months; 0.3 microg day(-1) during
      the next four months). At the end of the cultivation period, 42% of all
      phenylpyrazole compounds remained in the seed-coat. Fipro nil was poorly mobile
      in soil, and at the end of the cultivation period it was mostly concentrated in
      the soil layer close to the seed (3240 microg kg(-1) soil). Starting from the
      seed-coating, a fipronil concentration gradient was measured in the soil, up to a
      distance of 11 cm from the seed. Degradation in the soil occurred at a moderate
      rate, probably due to the fact that water solubilization of the solid active
      ingredient present in the seed coating was rate limiting. Indeed, after 6 months
      of cultivation, only 51% of the fipronil seed-coating was found in the soil,
      about 7% having been absorbed by the sunflower plant, and 42% remaining in the
      seed coat. The predominant metabolites produced in the soil were sulfone
      fipronil, sulfide-fipronil and amide-fipronil, which were produced at average
      rates of 5 microg kg(-1) soil day(-1), 3 microg kg(-1) soil day(-1), and 0.4
      microg kg(-1) soil day(-1), respectively. In contrast, the photoproduct,
      desulfinyl-fipronil, was barely detected. All phenylpyrazole compounds were
      poorly mobile, except for the amide derivative, which is devoid of insecticidal
      activity in marked contrast to the other metabolites. Furthermore, detectable
      soil contamination was limited to a zone of about 11 cm around the seed.

PMID- 17509642
TI  - Inocula from activated sludge for ready biodegradability testing: homogenization
      by preconditioning.
AB  - The use of activated sludge as inoculum source in ready biodegradability tests
      (RBT) suffers from several drawbacks related to the heterogeneity of these
      communities. In this work, the ability of a 7-day aeration period in a mineral
      medium to homogenize the characteristics of various activated sludges, as
      suggested by some RBT, was studied. The biodegradation potential of three
      activated sludge supernatants obtained from different wastewater treatment plants
      was assessed in terms of cultivable cell density, dehydrogenasic activity and a
      profile of hydrolytic enzymes. After the preconditioning, the homogenization of
      these characteristics in the supernatants was observed, as well as a decrease.
      When preconditioned inocula were used in acetate RBT, the biodegradation kinetics
      were homogenized. However, some preconditioned supernatants lost their ability to
      degrade an easily-assimilable xenobiotic compound (aniline) during the
      observation period, showing the effect of inoculum preconditioning on the
      behavior of complex bacterial communities, specialist populations (e.g. aniline
      degraders) being more sensitive than generalist populations (e.g. acetate
      degraders). These results show that preconditioning cannot be an optional
      inoculum pretreatment in RBT, and emphasize the importance of further studies
      focusing on inoculum homogenization.

PMID- 17509643
TI  - Development and verification of a toxicokinetic model of polychlorinated biphenyl
      elimination in persons working in a contaminated building.
AB  - BACKGROUND: Polychlorinated biphenyls are toxic and slowly degrading substances
      that have been in widespread industrial use in the 1960s and 1970s. Despite a
      worldwide reduction, environmental exposure remains an issue; the assessment of
      an individual's level of exposure at a given time in retrospect requires valid
      toxicokinetic modeling of the different PCB congeners. OBJECTIVES: To develop and
      verify a toxicokinetic model of the in vivo-degradation of PCB 28 and 52 in adult
      humans. METHODS: The plasma concentrations of PCB congeners were measured in 583
      persons working in a contaminated building for an average of 14.7+/-9.6 years.
      The values were adapted to a simple pharmacokinetic model (yt = y0 x (1 - e(
      kt))); the steady state concentration y0 was estimated based on the median values
      of persons working exposed more than 10 years. RESULTS: The steady state
      concentration of PCB 28 was 0.10 microg/l, that of PCB 52 0.02 microg/l. The half
      life of the congeners was estimated based on a logarithmic regression analysis
      according to the model mentioned above; it was 2.18 (95% CI: 1.91-2.54) years for
      PCB 28 and 3.95 (95% CI: 3.55-4.45) years for PCB 52, respectively. Stepwise
      elimination of persons with very long employment duration did not reduce the
      estimated half-life. CONCLUSIONS: The estimated half-life is higher than
      previously published data especially for PCB 52. Possible reasons and
      implications of this finding are discussed.

PMID- 17509644
TI  - A congener-specific survey for polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs) contamination in Masan Bay, Korea.
AB  - A congener-specific determination of polychlorinated dibenzo-p-dioxins (PCDDs)
      and polychlorinated dibenzofurans (PCDFs) in 21 surface sediments from Masan Bay,
      Korea revealed that the most toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8
      TCDD) was detected in 76% of the samples and 2,3,7,8-tetrachlorodibenzofuran
      (2,3,7,8-TCDF) in 100% of the samples analyzed. The concentration range of
      SigmaPCDDs and SigmaPCDFs are: 230-6900; 120-16700pgg(-1) dry mass respectively.
      WHO Toxic Equivalents (WHO-TEQ) in Masan Bay sediment ranged from 0.53 to 99ng
      TEQkg(-1)d.m. for PCDDs; 4 to 1300ngTEQkg(-1)d.m. for PCDFs. In comparison with
      an earlier survey, the concentrations of dioxins and furans have more than
      doubled and the SigmaWHO-TEQ values have increased 15 times within a decade. Both
      point and non-point sources of pollution are suspected, especially, local sewage
      treatment plants are found to contribute.

PMID- 17509645
TI  - Acute and chronic toxicities of tributyltin to various life stages of the marine
      polychaete Hydroides elegans.
AB  - Experiments were performed to determine the acute and chronic toxicities of
      tributyltin (TBT) (nominal concentrations) to polychaete Hydroides elegans.
      Firstly, static tests were performed to examine the lethal effect of TBT on five
      life stages of H. elegans. The 48-h LC(50) (95% CI) for the eggs, 2-cells,
      trochophores, juveniles and adults was 0.18 (0.15-0.20), 0.97 (0.77-1.23), 2.36
      (2.11-2.65), 2.86 (2.63-3.12) and 4.36 (4.04-4.71) microg TBT l(-1),
      respectively. Secondly, a 17-d static renewal chronic test was conducted to study
      sensitivity of the early development (egg to juvenile) to TBT. The survivorship,
      percent settlement and time to reach settlement were significantly reduced at
      0.01 microg TBT l(-1). Effects of TBT on the juvenile growth and maturation were
      also studied through a 44-d chronic test. Lower survivorship and reduced tube
      growth were observed only at >or= 1 microg TBT l(-1), however, only H. elegans
      exposed to <or= 0.1 microg TBT l(-1) reached maturity. The final experiment
      examined effects of TBT on the fecundity of female worms through a 60-d chronic
      test. Although survivorship remained high even at 1 microg TBT l(-1), egg
      production, success in fertilization and egg development were all reduced at >or=
      0.1 microg TBT l(-1). Our results indicate that the early development of H.
      elegans is highly sensitive to TBT and this polychaete can be routinely employed
      as a test organism for both acute and chronic ecotoxicity bioassays in tropical
      and subtropical regions such as southern China.

PMID- 17509646
TI  - Simultaneous monitoring of PCDD/Fs and PCBs in contaminated air with
      semipermeable membrane devices and fresh spruce needles.
AB  - The contaminated air with burning plastic floor and electronic scrap was
      monitored with semipermeable membrane devices (SPMDs) and fresh unpolluted spruce
      needles at the same time for polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs). It
      was found that there were more polychlorinated dibenzofurans (PCDFs) than
      polychlorinated dibenzo-p-dioxins (PCDDs) collected from contaminated air. The
      total amounts of PCBs were much higher than that of PCDD/Fs, but the contribution
      of them to the WHO-TEQ was less than that of PCDD/Fs. Triolein-containing SPMDs
      can absorb much more PCDD/Fs and PCBs than spruce needles when they were exposed
      in contaminated air simultaneously. The logarithm of the concentrations of
      PCDD/Fs and PCBs in SPMDs and in spruce needles at the same sampling time
      exhibited a significant linear correlation, the correlation coefficients were
      larger than 0.86 for PCDD/Fs and 0.92 for PCBs. SPMDs and spruce needles are
      effective passive air sampler for PCDD/Fs and PCBs. SPMDs and spruce needles can
      complement each other in passive air sampling.

PMID- 17509647
TI  - Distribution of dioxins, furans, and dioxin-like PCBs in solid products generated
      by pyrolysis and melting of automobile shredder residues.
AB  - Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like
      polychlorinated biphenyls (PCBs) in char and slag produced from automobile
      shredder residue by pyrolysis and melting process were analyzed to measure
      changes in the characteristics and distribution of their congeners caused by
      thermal treatment. In particular, a large quantity of dioxin-like PCBs occurred
      in low-chlorinated congeners. The concentration of PCDDs/PCDFs in char was 0.542
      microg/kg, with mostly PCDFs dominant and its toxicity equivalent concentration
      (TEQ) was about 70ngTEQ/kg. The concentration and toxicity equivalent
      concentration of dioxin-like PCBs in char were 0.869 microg/kg and 1.60ngTEQ/kg,
      respectively. Melted char slag was produced using various cooling methods: water
      quenching, air cooling, and slow cooling. The concentrations of PCDDs/PCDFs in
      slag produced by the methods were 1.51, 1.38, and 2.43ngTEQ/kg, respectively;
      those of dioxin-like PCBs were close to 0.01ngTEQ/kg. The congener distributions
      varied only slightly among the cooling methods. Applying melting procedure to
      char reduced PCDD/PCDF concentration by 95.3%, and the corresponding TEQ
      concentration was reduced by 97.9%. We thus conclude that melting process is an
      efficient way to reduce the concentrations of PCDDs/PCDFs in solids produced by
      pyrolysis.

PMID- 17509648
TI  - Organic pollutants abatement and biodecontamination of brewery effluents by a non
      thermal quenched plasma at atmospheric pressure.
AB  - A preliminary study was carried out to investigate possible decontamination of
      the waste waters from a Cameroonian brewery by using a non-thermal atmospheric
      plasma. Samples of waste waters collected during periods of intense activity of
      production were first analysed for organoleptic, physical-chemical and organic
      parameters, and then exposed to a humid air electric discharge at ambient
      temperature and pressure. The resultant pollution abatement and germicidal
      effects are both ascribed to strong oxidising effects of OH and NO radicals
      formed in the plasma. The BOD removal efficiency of the process with brewery
      industrial wastewaters under BOD concentration of 385 and 1018 mg l(-1) were 74%
      and 98% respectively. The alkaline wastewaters are rapidly neutralised due to the
      pH lowering effects of the plasma treatment.

PMID- 17509649
TI  - Characterization and inventory of PCDD/F emissions from coal-fired power plants
      and other sources in Taiwan.
AB  - The objectives of the present study were to quantify (1) the emission factors of
      a variety of dioxin emission sources; (2) the overall dioxin emission inventory
      in Taiwan as well as in a major metropolitan (KC area); and (3) the contribution
      of power plants to the overall PCDD/F emission. To achieve these goals, a total
      of 95 flue gas samples were collected and analyzed for 17 PCDD/Fs from 20 sources
      to develop emission factors. The emission factor of PCDD/Fs from coal-fired power
      plants (0.62 microgI-TEQton(-1)) obtained in this study is considerably higher
      than the values reported from different countries including UK, USA, and Spain by
      a factor of 2-265. It means that the air pollution control devices in certain
      power plants need to be more efficient. The emission data showed that there is a
      total annual release to air of 6.1 and 95gI-TEQ from major sources in the KC area
      and Taiwan, respectively. The dominant sources of PCDD/Fs in the KC area are the
      coal-fired power plants, secondary aluminum smelting, electric arc furnaces, and
      open burning of rice straw, which contributed for 56%, 17%, 13%, and 3.3% to the
      total, respectively. However, in Taiwan, the dominant sources of PCDD/Fs are the
      iron ore sintering, coal-fired power plants, electric arc furnaces, and open
      burning of rice straw, which contributed for 32%, 28%, 23%, and 8.1% to the
      total, respectively. The results of this study showed that coal-fired power
      plants are very significant sources of PCDD/Fs and also provide an important
      database to assist the decision makers for formulating policies to alleviate
      dioxin concerns.

PMID- 17509650
TI  - Occurrence of organic contaminants in sewage sludges from eleven wastewater
      treatment plants, China.
AB  - This study presents the occurrence of 43 semi-volatile organic compounds (SVOCs)
      listed as priority pollutants by both China and the United States Environmental
      Protection Agency, in sewage sludges collected from eleven wastewater treatment
      plants (WWTPs) of mainland and Hong Kong, China. Thirty-six SVOCs were detected
      by gas chromatography coupled with mass spectrometer (GC-MS) and at least 14 in
      each sample. The most abundant compounds were phthalic acid esters (PAEs) and
      polycyclic aromatic hydrocarbons (PAHs) with total concentrations ranging from 10
      to 114mgkg(-1) dry weight (d.w.) (with a mean of 30mgkg(-1) d.w.) and from 1.4 to
      33mgkg(-1)d.w. (with a mean of 16mgkg(-1) d.w.), respectively, followed by
      chlorobenzenes, nitroaromatics, haloethers and halogenated hydrocarbons which
      occurred generally at concentrations lower than 10mgkg(-1) d.w. Large variations
      were observed between the concentrations of individual compounds as well as their
      total concentrations in sludge samples from different WWTPs. The highest values
      of sum concentration of 16 PAHs and of 6 PAEs were found in sewage sludge from
      Beijing. The mean total concentration of each class of SVOCs in sewage sludge
      from mainland was remarkably higher than that from Hong Kong. The concentrations
      of di(2-ethylhexyl) phthalate in 91% sludge samples met the limit (100mgkg(
      1)d.w.) proposed by the Europe Union for land application, whereas the PAH
      concentrations of 64% sludge samples exceeded the maximum permissible
      concentration (6.0mgkg(-1)d.w.). The occurrence of SVOCs in this study are
      compared with other studies and their sources are discussed.

PMID- 17509651
TI  - Stabilization of FGD gypsum for its disposal in landfills using amorphous
      aluminium oxide as a fluoride retention additive.
AB  - The applicability of amorphous aluminium oxide as a fluoride retention additive
      to flue gas desulphurisation (FGD) gypsum was studied as a way of stabilizing
      this by-product for its disposal in landfills. Using a batch method the sorption
      behaviour of amorphous aluminium oxide was evaluated at the pH (about 6.5) and
      background electrolyte conditions (high chloride and sulphate concentrations)
      found in FGD gypsum leachates. It was found that fluoride sorption on amorphous
      aluminium oxide was a very fast process with equilibrium attained within the
      first half an hour of interaction. The sorption process was well described by the
      Langmuir model, offering a maximum fluoride sorption capacity of 61.7 mg g(-1).
      Fluoride sorption was unaffected by chloride co-existing ions, while slightly
      decreased (about 20%) by competing sulphate ions. The use of amorphous aluminium
      oxide in the stabilization of FGD gypsum proved to greatly decreased its fluoride
      leachable content (in the range 5-75% for amorphous aluminium oxide doses of 0.1
      2%, as determined by the European standard EN 12457-4 [EN-12457-4
      Characterization of waste-leaching-compliance test for leaching of granular waste
      materials and sludges-Part 4: one stage batch test at a liquid to solid ratio of
      10 l/kg for materials with particle size below 10mm (without or with size
      reduction)]), assuring the characterization of this by-product as a waste
      acceptable at landfills of non-hazardous wastes according to the Council Decision
      2003/33/EC [Council Decision 2003/33/EC of 19 December 2002. Establishing
      criteria and procedures for the acceptance of waste at landfills pursuant to
      Article 16 of and Annex II to Directive 1999/31/EC] on landfill of wastes.
      Furthermore, as derived from column leaching studies, the proposed stabilization
      system proved to be highly effective in simulated conditions of disposal,
      displaying a fluoride leaching reduction value about 81% for an amorphous
      aluminium oxide added amount of 2%.

PMID- 17509652
TI  - Electrochemical destruction of p-chlorophenol and p-nitrophenol -- Influence of
      surfactants and anode materials.
AB  - The electrochemical oxidative removal of p-chlorophenol and p-nitrophenol was
      studied by cyclic voltammetry (CV) and constant current electrolysis on
      commercially available graphite and titanium substrate insoluble anodes (TSIA).
      The effect of cationic cetyl trimethylammonium bromide (CTAB), anionic sodium
      dodecyl sulphate (SDS) and non-ionic polyoxyethylene(23)lauryl ether (Brij-35)
      surfactants, which prevent adherent film formation on the electrode surface were
      also studied. CV experiments indicate that p-chlorophenol exhibits a relatively
      higher tendency for film formation on graphite and that sodium chloride is a
      better medium for the destruction of phenols. The electrochemical oxidation of
      phenols under galvanostatic conditions in chloride medium with CTAB enhanced the
      detoxification process with significantly lower fouling effects on TSIA. The
      surfactants, however, did not improve phenol removal on graphite under identical
      experimental conditions. A charge of 2.5F per mol was found to be sufficient to
      achieve 44-48% removal of phenol on both the electrodes in the absence of the
      surfactants. A 55-65% removal was achieved in the presence of the cationic
      surfactant on the TSIA electrode. Phenol was removed as a low molecular weight
      polymer (MW approximately 4450).

PMID- 17509653
TI  - Sources of adsorbable organic halogens (AOX) in sludge of Gaza.
AB  - Average concentrations of adsorbable organic halogens (AOX) in sludge from the
      Gaza Strip reached 600 mg kg(-1) which currently represents a major limiting
      factor for sludge application in agriculture. This study aims to identify the
      main sources of AOX in Gaza where the area is small with limited industrial
      activities. The results showed that the AOX in effluent sludge is formed mainly
      inside the treatment plant. Although the plant receives AOX wastewater of only 85
      microg l(-1), this value increased five fold inside the plant to an average of
      400 microg l(-1) in the effluent wastewater. On the other hand, the sludge from
      the first sedimentation pond showed an AOX concentration of 213 mg kg(-1) and
      increased in the final sedimentation pond to 500 mg kg(-1). The AOX concentration
      in three month old sludge was 130 mg kg(-1). The textile and detergent industries
      are the major AOX producing industries in Gaza, with an average AOX of 40,000
      microg l(-1) in their effluent wastewater. These values do not represent a
      significant AOX pollution load to the treatment plant because these industries
      are very limited and their effluents are diluted before entering the municipal
      treatment plant. Industrial activity decreased in 2006 to less than 70% of the
      previous four years. Consequently, the AOX in the industrial effluent decreased
      from 150,000 to 40,000 microg l(-1) over the same time period. Sludge from these
      industries showed 1300 mg kg(-1) AOX for the past four years and only 400 mg kg(
      1) in 2006. Moreover, the AOX in the influent wastewater discharged to the
      treatment plant decreased from 320 to 85 microg l(-1) for the same period. This
      study revealed that the major AOX is formed inside the treatment plant and
      especially in the anaerobic facilities. There was no correlation between the AOX
      concentrations in the sludge and the wastewater at the same location. Moreover,
      there was no correlation between the AOX in sludge/wastewater and dissolved
      oxygen, pH and chloride in that treatment plant.

PMID- 17509654
TI  - Polybrominated diphenyl ethers and organochlorine pesticides in sewage sludge of
      wastewater treatment plants in China.
AB  - The concentrations of chemicals in sewage sludge from wastewater treatment plants
      (WWTPs) may relate to their levels of use and environmental pollution in the
      region. In this work, sludge samples were collected from 31 WWTPs in 26 cities in
      China and analyzed for polybrominated diphenyl ethers (PBDEs) and organochlorine
      pesticides (OCPs). The concentrations of SigmaPBDE (sum of congeners 17, 28, 47,
      66, 71, 85, 99, 100, 138, 153, 154, and 183) ranged from 6.2 to 57ng/g (dw). The
      concentration of decabromodiphenyl ether (BDE-209) ranged from below limit of
      detection (LOD) to 1109ng/g (dw) (with a median of 27ng/g (dw)), and averaged 55%
      (median 69%) of the total PBDEs. These levels are about 10-100 times lower than
      those found in Europe and North America. PBDE levels in sludge were not found to
      depend on the location and capacity of the WWTPs. Concentrations of
      hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethane (DDTs) and its
      major degradation products, and hexachlorobenzene (HCB) ranged from below
      detection limit to 167ng/g (dw), 11 to 1065ng/g (dw), and 7.5 to 319ng/g (dw),
      respectively. The major DDT degradation products were p,p'-DDE and p,p'-DDD. The
      major hexachlorocyclohexane (HCH) isomer in sludge is beta-HCH, reflecting its
      higher affinity to solids and resistance to degradation than other isomers.

PMID- 17509655
TI  - An expanded reaction kinetic model of the CuO surface-mediated formation of
      PCDD/F from pyrolysis of 2-chlorophenol.
AB  - An expanded reaction kinetic model, including 17 surface reactions, is proposed
      to explain the yields of PCDD/F obtained in an experimental study of the reaction
      of 2-chlorophenol over a CuO/silica surface. The mechanism is loosely based on
      the gas-phase mechanism for PCDD/F formation widely discussed in the literature.
      The principal differences are the impact of chemisorption of 2-chlorophenols to
      metal oxides on radical formation and the steric hindrance of oxygen-centered
      radicals on the surface inhibiting radical-radical reaction pathways that lead to
      formation of dibenzo-p-dioxin (DD). Gas-phase molecule-surface-bound adsorbate
      reactions are the preferred route of DD formation, while radical-radical surface
      reactions are the main channel for dichloro-dibenzofuran (DCDF) formation. These
      results suggest that the Langmuir-Hinshelwood (LH) mechanism, involving radical
      radical surface reactions, and the Eley-Rideal mechanism, involving a gas-phase
      molecule and surface-bound adsorbate, are responsible for PCDF and PCDD formation
      on surfaces, respectively. The calculated yields of DCDF and DD are in reasonable
      agreement with experimental results.

PMID- 17509656
TI  - Occurrence of polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls
      pollution in sediments from the Haihe River and Dagu Drainage River in Tianjin
      City, China.
AB  - The pollution status of polychlorinated dibenzo-p-dioxins, dibenzofurans
      (PCDD/Fs) and polychlorinated biphenyls (PCBs) in the sediments of Haihe River,
      which is the most polluted among the seven largest basins in China, Dagu Drainage
      River flowing through a chemical industry zone, and two other rivers flowing into
      Bohai Sea in Tianjin City, China were investigated. The concentrations of PCDD/Fs
      and PCBs in the sediments from the mainstream of Haihe River were 1.3-26pgI-TEQg(
      1) dry weight (dw) and 0.07-0.54pgTEQg(-1)dw, respectively. Heavy PCDD/Fs and
      PCBs pollution, with 1264pgI-TEQg(-1)dw and 21pgTEQg(-1)dw, was found in sediment
      from Dagu Drainage River. The congener profiles of PCDD/Fs indicated that the
      principal contamination source was the production of pentachlorophenol (PCP) or
      PCP-Na in this area. The correlation between PCDD/Fs or PCBs and total organic
      matter (TOM) showed that PCDD/Fs or PCBs were independent on TOM.

PMID- 17509657
TI  - Arsenic accumulation in duckweed (Spirodela polyrhiza L.): a good option for
      phytoremediation.
AB  - Some unavoidable drawbacks of traditional technologies have made phytoremediation
      a promising alternative for removal of arsenic from contaminated soil and water.
      In the present study, the potential of an aquatic macrophyte Spirodela polyrhiza
      L. for phytofiltration of arsenic, and the mechanism of the arsenic uptake were
      investigated. The S. polyrhiza L. were grown in three test concentrations of
      arsenate and dimethylarsinic acid (DMAA) (i.e. 1.0, 2.0 and 4.0microM) with 0
      (control), 100 or 500microM of phosphate. One control treatment was also set for
      each test concentrations of arsenic. The PO(4)(3-) concentration in control
      treatment was 0.02microM. When S. polyrhiza L. was cultivated hydroponically for
      6d in culture solution containing 0.02microM phosphate and 4.0microM arsenate or
      DMAA, the arsenic uptake was 0.353+/-0.003micromolg(-1) and 7.65+/-0.27nmolg(-1),
      respectively. Arsenic uptake into S. polyrhiza L. was negatively (p<0.05)
      correlated with phosphate uptake when arsenate was applied to the culture
      solutions owing to similar in the sorption mechanism between AsO(4)(3-) and
      PO(4)(3-), and positively (p<0.05) correlated with iron uptake due to adsorption
      of AsO(4)(3-) onto iron oxides. Thus, the S. polyrhiza L. accumulates arsenic by
      physico-chemical adsorption and via the phosphate uptake pathway when arsenate
      was added to the solutions. These results indicate that S. polyrhiza L. would be
      a good arsenic phytofiltrator. In contrast, DMAA accumulation into S. polyrhiza
      L. was neither affected by the phosphate concentration in the culture nor
      correlated (p>0.05) with iron accumulation in plant tissues, which indicates that
      S. polyrhiza L. uses different mechanisms for DMAA uptake.

PMID- 17509658
TI  - Long-term fate of three hexachlorocyclohexanes in the lower reach of Liao River
      basin: dynamic mass budgets and pathways.
AB  - The Liao River Basin Multimedia Fate and Transport Model (LRBMFTM), a non-steady
      state multiple-segment river fugacity-based model, for describing the long-term
      fate of persistent organic pollutants (POPs) in Liao River basin environment, is
      used to illustrate a quantitative understanding of the behavior of alpha-, beta-,
      and gamma-hexachlorocyclohexane (HCH) in more detail in the lower reach of Liao
      River basin from 1952 to 2001. The major pathway of the three HCHs from the basin
      to the surrounding environment is the atmospheric advection. One of the major
      removing of HCHs from the basin is degradation, where 2388.5 ton of alpha-HCH,
      405.6 ton of beta-HCH, 382.7 ton of gamma-HCH emitted into the basin have been
      degraded, especially in the soil of application regions. The main reservoir of
      the HCHs is the soil in the basin, where there is a positive correlation between
      the accumulated amount and emission. The model suggests that the mass fluxes of
      all processes show an obviously seasonal trend. After the use ban, HCHs evaporate
      from water bodies, soils, and vegetation, and are advected away in the
      atmosphere. It is believed that the model can provide a valuable understanding of
      the processes that determine the overall fate of HCHs in the basin.

PMID- 17509659
TI  - PCB contamination in farmed and wild sea bass (Dicentrarchus labrax L.) from a
      coastal wetland area in central Italy.
AB  - Food consumption is by far the main exposure route for polychlorinated biphenyls
      (PCBs) for the general population, and fish and fishery products seem to be the
      main contributors to the total dietary intake of these pollutants. In recent
      years some investigations have suggested that farmed fish may be more
      significantly contaminated than wild fish, because of polluted feed. This study
      measured the levels of PCBs in wild and farmed sea bass (Dicentrarchus labrax
      L.), one of the most valuable and popular fish in the Italian diet, and assessed
      the exposure to these pollutants through fish intake. Concentrations of summation
      operator (Sigma59PCBs) and dioxin-like PCBs (DL-PCBs), as toxic equivalency
      (TEQ), in fish samples, ranged from 2.2 to 32ngg(-1) and from 0.1 to 4.0pg
      TEQ((2006) DL-PCBs)g(-1) whole weight, respectively. Farmed sea bass were as
      average two times more contaminated. Even if the concentrations of DL-PCBs were
      below the regulation limits, intake of these compounds from nine fish meals per
      month can in itself exceed the WHO Provisional Tolerable Monthly Intake (PTMI).

PMID- 17509660
TI  - Evaluation of NF2 gene deletion in sporadic schwannomas, meningiomas, and
      ependymomas by chromogenic in situ hybridization.
AB  - Fluorescence in situ hybridization, loss of heterozygosity testing, and
      comparative genomic hybridization have been used to detect NF2 gene alterations
      in both sporadic and neurofibromatosis type 2 (NF2)-associated central nervous
      system tumors. In this study, we performed chromogenic in situ hybridization
      (CISH) and immunohistochemistry to evaluate for NF2 gene deletion in a group of
      sporadic meningiomas, schwannomas, and ependymomas. Twenty-two sporadic tumors,
      including 9 ependymomas, 10 meningiomas, and 3 schwannomas, were studied. CISH
      and immunohistochemistry were performed using the NF2 gene deletion probe and NF2
      polyclonal antibody. Deletion of the NF2 gene was identified in 11 (50%) tumors,
      including 60% (6/10) of meningiomas, 33% (3/9) of ependymomas, and 67% (2/3) of
      schwannomas. The remaining 11 (50%) cases were diploid. Overall, immunoexpression
      of NF2 protein was observed in 50% (11/22) tumors, and concordance between CISH
      and immunohistochemistry was observed in 73% of cases. Our results support
      previous observations that schwannomas and meningiomas, and to a lesser degree,
      ependymomas, express a high incidence of NF2 gene deletion, which supports the
      hypothesis that NF2 gene plays an important role in their tumorigenesis. In
      addition, we have validated CISH as an efficient, economic, and reliable method
      for routinely assessing NF2 gene deletion in these tumors.

PMID- 17509661
TI  - Epidermal growth factor receptor in osteosarcoma: expression and mutational
      analysis.
AB  - Activation of intracellular mitogenic signal transduction pathways driven by the
      ErbB family of receptor tyrosine kinases has been implicated in the development
      and/or progression of a variety of cancers. Studies on ErbB receptors in
      osteosarcoma have focused on HER-2 and have produced conflicting results with few
      studies evaluating the expression of the epidermal growth factor receptor (EGFR).
      In this study, we determined the level of expression of EGFR and the mutational
      status of the EGFR receptor in a subset of osteosarcoma tumor samples as well as
      in a series of established bone tumor-derived cell lines. EGFR protein expression
      was detected in the form of strong membranous staining by immunohistochemistry in
      21 (57%) of 37 cases analyzed. Six of 12 (50%) osteosarcoma cell lines revealed
      moderate to high expression levels of EGFR. Two somatic alterations (E829E and
      R831C) were identified in the cytoplasmic domain of the EGFR gene in 1 of 10
      tumor samples. The significance of these findings for the pathobiology of
      osteosarcomas will be investigated further.

PMID- 17509662
TI  - A doctor in the house.

PMID- 17509663
TI  - Human scribble accumulates in colorectal neoplasia in association with an altered
      distribution of beta-catenin.
AB  - The loss of epithelial polarity and tissue architecture is a diagnostic feature
      of malignant tumors. In Drosophila, genetic studies identified 3 neoplastic tumor
      suppressor genes (nTSGs), and a loss of nTSGs has been shown to result in a
      disruption of apical-basal polarity and neoplastic growth in epithelial cells.
      Scribble is one type of the Drosophila nTSGs, which encodes a membrane-associated
      cytoplasmic protein containing the multi-PDZ domain. In contrast to Drosophila
      scribble, the oncogenic roles of its mammalian homologues have not yet been
      established. We herein immunohistochemically examined the distributions of hScrib
      protein in human colorectal neoplasia using affinity-purified antibody. In 50
      cases of colorectal adenomas and adenocarcinomas, the accumulation of hScrib
      protein was commonly observed in comparison with the adjacent normal epithelia.
      Furthermore, the overexpression and distribution of hScrib was observed to
      extensively overlap with the cytoplasmic accumulation of beta-catenin. Like beta
      catenin, the intense immunoreactivity of hScrib was often observed in small
      adenomas, thus, suggesting that hScrib could be involved in an early step of
      colon carcinogenesis. Five corresponding liver metastases showed a comparable
      immunoreactivity for anti-hScrib in comparison with their primary sites. In an
      immunofluorescence analysis on cultured cell lines, the loss of membranous
      staining of hScrib was observed according to the cytoplasmic translocation of
      beta-catenin. We herein demonstrate that the accumulation of hScrib protein might
      therefore be involved in colon carcinogenesis while also providing a possible
      link between hScrib and beta-catenin.

PMID- 17509664
TI  - Simulation-based process optimization for surfactant-enhanced aquifer remediation
      at heterogeneous DNAPL-contaminated sites.
AB  - Widespread use of dense non-aqueous phase liquids (DNAPLs) such as TCE and PCE
      has resulted in contamination of enormous valuable groundwater resources and
      become high-priority environmental problems. However, experiences from the past
      decades have demonstrated that DNAPL-contaminated sites were difficult to
      investigate and challenging to remediate. In this study, a simulation-based
      process optimization system was developed through integrating a multidimensional
      simulator, a multivariate statistical tool and an optimization model within a
      general framework for supporting decisions of surfactant-enhanced aquifer
      remediation (SEAR). A 3D multiphase and multi-component subsurface model was
      first provided to simulate SEAR process; dual-response surface models were then
      established to build a bridge between remediation actions and system performance;
      a nonlinear optimization model was then formulated for identifying optimal
      operating conditions for SEAR operations. The results in simulating a typical PCE
      spill event and the associated SEAR remediation operations in a heterogeneous
      subsurface indicated that SEAR would be capable of cleaning up the contaminated
      aquifer with improved efficiencies and cost-effectiveness compared with direct
      pump-and-treat actions. The regression-analysis results demonstrated that the
      proposed dual-response surface models were able to predict system responses under
      given operating conditions. The optimization results demonstrated that the
      developed simulation-optimization approach was effective in seeking cost
      effective SEAR strategies for DNAPL-contaminated sites. With the developed
      method, optimum operation conditions under various environmental and economic
      considerations could be compiled into a database that would supports further
      studies of on-site process-control with injection and extraction rates being the
      main control variables.

PMID- 17509665
TI  - Selenium level in the environment and the population of Zhoukoudian area,
      Beijing, China.
AB  - The objective of this study was to detect the selenium level in the environment
      and the population of Zhoukoudian area, Beijing, and to discuss the influence of
      various factors on serum selenium level. The soil, drinking water, and foodstuff
      samples and venous blood samples of 401 individuals were obtained to determine
      the selenium level by gas chromatograph equipped with a (63)Ni electron capture
      detector (ECD). The selenium level was 0.210+/-0.013 microg/g in soil, 0.017
      microg/L+/-0.002 in drinking water, 0.034+/-0.002 microg/g in rice, and 0.034+/
      0.012 microg/g in wheat flour. This index showed that the Zhoukoudian area of
      Beijing was a moderate or marginal level selenium ecological landscape. The mean
      serum selenium level of the population was 75.01+/-28.35 microg/L, ranging
      between 35.2 and 160.4 microg/L. A total of 279 (69.6%) individuals exhibited
      serum selenium level below 80 microg/L, which is the lowest threshold for the
      activity of glutathione peroxidases (GPx) in vivo. A total of 35 (8.5%)
      individuals exhibited serum selenium level below 45 microg/L. It is widely
      recommended that below this value (45 microg/L) there is an increased risk of
      cardiovascular disease and cancer. Multiple linear regression analysis showed
      that serum selenium level was positively associated with body mass index
      (beta=0.137; P=0.011), serum total cholesterol TC (beta=0.785; P=0.000), however,
      negatively associated with systolic blood pressure (beta=-0.172; P=0.023), serum
      triglyceride (beta=-0.170; P=0.007), high density lipoprotein-cholesterol (beta=
      0.121; P=0.027), and low high density lipoprotein-cholesterol (beta=-0.568;
      P=0.027).

PMID- 17509666
TI  - Lithological and pedological influences on the magnetic susceptibility of soil:
      their consideration in magnetic pollution mapping.
AB  - Magnetic susceptibility measurements are widely used to map and monitor the heavy
      metal pollution of soils. However, the magnetic properties of soils are
      influenced significantly by the bedrock lithology and soil-forming processes.
      Therefore, a main challenge in the data interpretation is to filter out the
      anthropogenic pollution signal. In this study we address this problem by
      analysing susceptibility values, heavy metal concentrations, as well as
      pedological parameters in a large soil data set from the eastern segment of
      Austria, covering a wide range of different lithologies and soil types. The
      statistic assessment demonstrates an influence of lithology and soil type on the
      magnetic susceptibility signal. Therefore anomalies are defined in sub sets of
      different soil types separately. Three different methods were applied to detect
      susceptibility anomalies: the median absolute deviation method, the boxplot
      method, and the population modelling method. These methods evaluate topsoil data
      only and can therefore also be applied to field measurements of magnetic
      susceptibility. The results were compared to the conventional method of
      calculating the difference of topsoil and subsoil susceptibility. All three
      approaches identify the main anomalies in the study area and are successful in
      circumventing the problem of erroneous anomaly definition due to pedological
      processes. However, knowledge of the lithological background is still necessary
      for a meaningful interpretation and can only be substituted by a large amount of
      data. The tested methods lead to thresholds of different height and therefore act
      as filters of different strength for the definition of anomalies.

PMID- 17509667
TI  - Simultaneous removal of chlorothalonil and nitrate by Bacillus cereus strain NS1.
AB  - Elevated NO3- and chlorothalonil (CTN) have been found in production nursery
      recycling ponds. Bacillus cereus strain NS1 isolated from nursery recycling pond
      sediment was assessed for its ability to reduce NO3- and degrade CTN in a mineral
      medium. The results showed that the efficiency of NO3- reduction and CTN
      degradation by B. cereus strain NS1 were related to the nature of organic carbon
      sources added to the medium. In the medium amended with 100 mg/L yeast extract,
      86% of NO3- (100 mg/L) and 99% of CTN (78 microg/L) were simultaneously removed
      by B. cereus strain NS1 during the first day of the experiment. It took 6 days
      for the removal of 82-93% of NO3- and 87-91% of CTN in the media containing
      glucose and acetate. B. cereus strain NS1 needed organic carbon as energy sources
      and electron donors to respire NO3-, and simultaneously degrade CTN. These
      results suggest that B. cereus strain NS1 may have great potential to remediate
      NO3- and CTN contaminated water in nursery recycling ponds.

PMID- 17509668
TI  - Cancer in biopsy-proven giant cell arteritis. A population-based study.
AB  - OBJECTIVE: To investigate the potential association between giant cell arteritis
      (GCA) and cancer in a series of consecutive patients diagnosed with biopsy-proven
      GCA over a 25-year period at the single reference hospital for a well-defined
      population. METHODS: The case records of all patients diagnosed with biopsy
      proven GCA at the Department of Medicine of the Hospital Xeral-Calde (Lugo,
      Northwest Spain) between January 1, 1981 and December 31, 2005 were reviewed.
      Information on cancer and cause of death over the extended follow-up was
      assessed. In all cases the presence of cancer was histologically confirmed.
      RESULTS: Cancer was found in 39 (15.3%) of the 255 GCA patients. Although 7 (18%)
      of the 39 patients had cancer either at the time or within the first 12 months
      after GCA diagnosis, the standardized mortality ratio (SMR) due to cancer in
      patients with biopsy-proven GCA showed no increase (overall SMR 1.06 [0.65-1.60];
      men, 0.81; women, 1.50). The time interval between GCA diagnosis and cancer
      diagnosis was 5.2+/-3.8 years (median 4.2 years; interquartile range: 3-7 years).
      When multivariate analysis adjusted by age and sex was performed, only the
      presence of dysphagia (adjusted hazards ratio (HR)=3.90; P=0.04), abnormal
      temporal artery on physical examination (adjusted HR=4.61; P=0.04), and anemia at
      the time of GCA diagnosis (adjusted HR=3.39; P=0.01) were associated with an
      increased risk of cancer over the extended follow-up. CONCLUSION: The results
      from this series do not support an overall increase of mortality due to cancer in
      GCA.

PMID- 17509669
TI  - Reversible posterior leukoencephalopathy or leucoencephalopathy?

PMID- 17509670
TI  - Metabolic syndrome as a risk factor for deep vein thrombosis after acute cardiac
      conditions.

PMID- 17509671
TI  - Safety, feasibility, and costs of outpatient laparoscopic extraperitoneal aortic
      nodal dissection for locally advanced cervical carcinoma.
AB  - OBJECTIVE: To report on the safety, feasibility, and costs of outpatient
      laparoscopic extraperitoneal aortic lymph node dissection (LEPSS) for locally
      advanced cervical carcinoma. METHODS: A retrospective analysis of all outpatient
      LEPSS procedures performed at our institution between August 2005 and February
      2007 was performed. All patients with clinical stage IIB-IVA cervical carcinoma
      with no evidence of bulky aortic lymphadenopathy (>1.0 cm) on pre-operative
      computed tomography were offered the procedure. If present, pelvic nodal disease
      could not exceed greater than 1.5 cm. Records were reviewed for demographics,
      operative findings, complications, length of stay, and CT scan aortic nodal
      status. As a comparison, the average costs for outpatient LEPSS and outpatient
      CT, MRI, and PET scan at our institution were calculated. RESULTS: A total of
      eighteen outpatient LEPSS procedures were identified. The median age was 49 (22
      72). The median BMI was 29 (18-51). The median operative time was 108 min (60-135
      min). The median aortic nodal count was 10 (5-20 nodes). The median blood loss
      was 25 ml (10-50 ml). There were no intraoperative complications. There was no
      conversion from a retroperitoneal to a transperitoneal approach. No patient
      required overnight hospitalization. One patient experienced a lymphocyst
      postoperatively. There was no delay in the initiation of chemoradiation for any
      of the patients with a median onset of 10 days from the date of surgery. At least
      20% of the patients had one or more medical co-morbidities such as obesity,
      diabetes, hypertension, or a prior abdominal surgery. Occult aortic nodal
      metastasis was detected in 11% of the patients with a negative pre-operative CT
      scan. The average calculated costs at our institution for outpatient LEPSS was
      $5233 dollars versus $1520 dollars for CT scan, $4830 dollars for MRI and $5494
      dollars for a PET scan. CONCLUSIONS: To our knowledge this is the first reported
      experience of outpatient laparoscopic extraperitoneal aortic lymph node
      dissection for locally advanced cervical cancer. Outpatient LEPSS appears to be a
      safe and feasible procedure in the hands of an experienced surgeon, however
      further study is warranted. From a cost analysis perspective, outpatient LEPSS
      appears equivalent to PET scan and MRI, but is more expensive than CT scan.

PMID- 17509672
TI  - Cost-effectiveness of adjuvant radiotherapy in intermediate risk endometrial
      cancer.
AB  - OBJECTIVES: Endometrial cancer is the most common gynecologic malignancy in the
      United States. Adjuvant radiotherapy in patients with intermediate risk disease
      (stage IB, IC, and occult stage II) is controversial. Despite no proven survival
      advantage, a significant number of women undergo this treatment annually. The
      purpose of this study was to compare the estimated health and economic outcomes
      for adjuvant whole pelvic radiotherapy to no treatment with salvage therapy for
      recurrence. METHODS: A decision analytic model was created to estimate the costs
      of adjuvant pelvic radiotherapy versus no adjuvant radiotherapy in patients with
      intermediate risk endometrial cancer. Data used was gathered from published
      literature and institutional data on costs. The model incorporates complications,
      recurrence rates, treatment of recurrence, and survival in each group. RESULTS:
      In the base case analysis, adjuvant pelvic radiation reduced the recurrence rate
      by 50%. Cost-effectiveness as measured by cost per recurrence prevented was
      highly sensitive to the probability of recurrence and the efficacy of adjuvant
      therapy. In our model the mean costs of Strategy 1 with observation and treatment
      reserved until the time of recurrence would be $5016. In contrast the mean cost
      of Strategy 2 which incorporated adjuvant radiotherapy would be $21,159. Cost per
      recurrence prevented based on the incremental cost-effectiveness is thus
      $225,215. In the highest risk subgroup, using the upper limit of the 90%
      confidence limit of efficacy seen in GOG Protocol 99, cost/recurrence prevented
      was approximately $50,000. Results did not differ when using parameters solely
      from GOG 99 or PORTEC. CONCLUSIONS: Although adjuvant pelvic radiation does not
      appear to improve survival for intermediate risk endometrial cancer patients, it
      does prevent recurrences, at a net positive cost compared to no therapy. Data are
      not currently available to incorporate quality of life information into cost
      effectiveness analyses. Obtaining such data would allow cost/quality-adjusted
      life year gained to be estimated. This information is necessary to determine if
      the extra costs of adjuvant radiotherapy in patients with intermediate risk
      endometrial cancer are acceptable by current health care policy standards.

PMID- 17509673
TI  - Response and outcomes in elderly patients with stages IIIC-IV ovarian cancer
      receiving platinum-taxane chemotherapy.
AB  - OBJECTIVE: Recent reports have suggested that only half of women age > or =65
      with advanced ovarian cancer are treated with platinum-based chemotherapy. The
      objective of this study was to compare the response to platinum-taxane
      chemotherapy and subsequent outcomes between patients older and younger than 65
      years of age with stages IIIC-IV epithelial ovarian cancer (EOC). PATIENTS AND
      METHODS: A cohort study was performed of all patients with stages IIIC-IV EOC who
      had their primary surgery at our institution from 1998 to 2004 and subsequently
      began platinum-taxane chemotherapy. Main outcomes were response to primary
      chemotherapy, platinum resistance and progression-free (PFS) and overall survival
      (OS). RESULTS: A total of 292 patients began primary platinum-taxane therapy
      after surgery and comprised our study group. Of these, 108 (37%) were > or =65
      years old and 184 (63%) were <65. Stage of disease, optimal cytoreduction rate,
      number of chemotherapy cycles and chemotherapy regimen alterations were similar
      between groups. Patients > or =65 achieved a clinical complete response with a
      similar frequency to those <65 (70% vs. 79%) and had similar rates of platinum
      sensitivity at 6 months (61% vs. 65%). Patients > or =65 had equivalent PFS
      (P=0.99) and OS (P=0.36) to those <65. Age > or =65 years was not independently
      associated with impaired survival. CONCLUSIONS: Patients > or =65 years of age
      demonstrated similar rates of initial response, platinum resistance, PFS and OS
      to younger patients. Elderly women who can tolerate primary cytoreductive surgery
      should receive combination platinum-taxane chemotherapy.

PMID- 17509674
TI  - B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid
      adenocarcinomas and inversely correlated with tumor T-cell infiltration.
AB  - OBJECTIVES AND METHODS: B7-H4 (DD-O110), a member of the B7 family, negatively
      regulates T cell-mediated immune response. Previous studies have shown that B7-H4
      is highly expressed in endometrioid ovarian cancers with relatively low levels of
      expression in normal ovary which was confirmed by Western blot. The present study
      was designed to localize B7-H4 expression by immunohistochemistry (IHC) in normal
      endometrium, endometrial hyperplasia and uterine endometrioid adenocarcinoma. The
      pattern of B7-H4 localization was compared with the IHC detection of CD3 and CD8
      positive T lymphocytes and CD14 positive macrophages to investigate the role of
      B7-H4 in the regulation of tumor immune surveillance. B7-H4 expression was
      evaluated in apoptotic tumor cells. RESULTS: The proportion and intensity of B7
      H4 staining were increased in the progression from normal, hyperplastic and
      malignant endometrial glandular mucosa. B7-H4 showed a predominantly apical
      membranous staining (pattern 1) in normal and hyperplastic endometrial epithelium
      but showed intense circumferential membranous and cytoplasmic staining (pattern
      2) in a majority of endometrioid carcinoma cases (p=0.018). The proportion of B7
      H4 positive tumor cells and staining intensity was also higher in high risk
      tumors than in low risk tumors (p=0.001 and p=0.032, respectively). The
      proportion of B7-H4 positive tumor cells was inversely related to the number of
      CD3-positive and CD8-positive tumor-associated lymphocytes (TALs). There was a
      positive correlation between B7-H4 pattern 2 staining and both CD3-positive and
      CD8-positive tumor-infiltrating lymphocytes (TILs) (p=0.039 and p=0.031,
      respectively). CONCLUSIONS: B7-H4 is overexpressed in hyperplastic and malignant
      endometrial epithelium and is correlated with the number T cells associated with
      the tumor. These results suggest that B7-H4 overexpression may reflect a more
      aggressive biologic potential and may play a role in tumor immune surveillance
      mechanisms.

PMID- 17509675
TI  - Icariin from Epimedium brevicornum attenuates chronic mild stress-induced
      behavioral and neuroendocrinological alterations in male Wistar rats.
AB  - Chronic mild stress (CMS) is suggested to produce abnormalities in the
      hypothalamic-pituitary-adrenal (HPA) axis and hypothalamus-pituitary-thyroid
      (HPT) axis. Therefore, compound that attenuates the neuroendocrinological
      alterations may have potential as antidepressant. The behavioral and
      neuroendocrinological effects of icariin, a major constituent of flavonoids
      isolated from Epimedium brevicornum, were investigated in the CMS model of
      depression in male Wistar rats. CMS procedure caused an anhedonic state in rats
      resulted in increased corticotropin-releasing factor (CRF) concentrations in
      dissected brain regions and serum, decreased total triiodothyronine (tT3) in
      serum with no significant changes in serum adrenocorticotrophic hormone (ACTH)
      and thyroxine (tT4). Administration of icariin reversed CMS-induced sucrose
      intake reduction and CRF elevation. These results suggested that icariin
      possessed potent antidepressant-like activities which were at least in part
      mediated by improving the abnormalities in the HPA axis functions. However, we
      did not find a clear correlation between the HPT axis and icariin treatment in
      the CMS-treated rats.

PMID- 17509676
TI  - Decreased anxiety-like behavior in beta3 nicotinic receptor subunit knockout
      mice.
AB  - Nicotine, via a family of nicotinic acetylcholine receptors, elicits many
      physiological responses, including alterations in anxiety. Studies suggest that
      the effects of nicotine on anxiety may support smoking behaviors. We reported
      previously that mice lacking the beta3 nicotinic receptor subunit demonstrate
      increased activity in the open field arena. Open field activity has been shown to
      be a composite of anxiety and locomotor activity, behaviors that are both altered
      by nicotine. We therefore sought to differentiate the role(s) of beta3-containing
      receptors in anxiety and locomotor activity. Anxiety behaviors were examined in
      the elevated plus maze, the black/white box and the mirrored chamber. Beta3 null
      mutant mice demonstrated decreased anxiety with more time spent on the open arm
      of the elevated plus maze than their wildtype littermates. No significant
      differences were observed with the black/white box or the mirrored chamber.
      Levels of the stress hormone, corticosterone, were significantly higher in the
      beta3 null mutant mice at baseline and following exposure to stress. Increased
      locomotor activity in the Y-maze was also observed for the beta3 null mutant
      mice, but only following exposure to stress. These findings strongly suggest that
      beta3-containing nicotinic receptors influence anxiety and may be critical for
      the continuation of smoking behaviors.

PMID- 17509677
TI  - Non-smokers' responses when smokers light up: a population-based study.
AB  - OBJECTIVE: This study examines the extent to which the 'common courtesy approach'
      is adopted by non-smokers when in the presence of smokers, in the state of
      Victoria, Australia, where restrictions on smoking in public places are
      relatively comprehensive. METHOD: 4,765 non-smokers aged 18 years and over were
      surveyed over two representative population telephone-administered surveys of
      randomly sampled Victorians conducted in 2004 and 2005. RESULTS: Only 5.5% of non
      smokers said they would ask a person to stop smoking if they lit up a cigarette
      nearby. The majority of non-smokers (74.7%) reported they would move away and
      16.4% said they would do nothing. When asked what they would do if, in a public
      place, someone next to them asked if they minded whether they smoked, 48.8% of
      non-smokers reported they would say they would prefer it if they didn't smoke,
      while 28.0% reported that they would tell the person they don't mind when they
      would prefer that person not smoke. Overall, 46.7% of non-smokers indicated they
      would consent to be exposed to second-hand smoke if someone asked them this
      question. CONCLUSIONS: Our findings underline the importance of smoke-free
      policies in protecting a significant proportion of the non-smoker population, who
      remain unlikely to protect themselves individually.

PMID- 17509678
TI  - Radiosensitization of paclitaxel, etanidazole and paclitaxel+etanidazole
      nanoparticles on hypoxic human tumor cells in vitro.
AB  - Paclitaxel and etanidazole are hypoxic radiosensitizers that exhibit cytotoxic
      action at different mechanisms. The poly(D,L-lactide-co-glycolide) (PLGA)
      nanoparticles containing paclitaxel, etanidazole and paclitaxel+etanidazole were
      prepared by o/w and w/o/w emulsification-solvent evaporation method. The
      morphology of the nanoparticles was investigated by scanning electron microscope
      (SEM). The drug encapsulation efficiency (EE) and release profile in vitro were
      measured by high-performance liquid chromatography (HPLC). The cellular uptake of
      nanoparticles for the human breast carcinoma cells (MCF-7) and the human
      carcinoma cervicis cells (HeLa) was evaluated by transmission electronic
      microscopy and fluorescence microscopy. Cell viability was determined by the
      ability of single cell to form colonies in vitro. The prepared nanoparticles were
      spherical shape with size between 80 and 150 nm. The EE was higher for paclitaxel
      and lower for etanidazole. The drug release was controlled over time. The
      cellular uptake of nanoparticles was observed. Co-culture of the two tumor cell
      lines with drug-loaded nanoparticles demonstrated that released drug effectively
      sensitized hypoxic tumor cells to radiation. The radiosensitization of
      paclitaxel+etanidazole nanoparticles was more significant than that of single
      drug-loaded nanoparticles.

PMID- 17509679
TI  - The impact of 5-azacytidine on placental weight, glycoprotein pattern and
      proliferating cell nuclear antigen expression in rat placenta.
AB  - During the placentation process, the expression of various glycoproteins plays an
      important role in embryonal development. Alterations in DNA methylation caused by
      5-azacytidine (5azaC) can disturb normal glycoprotein expression as well as the
      proliferative ability of trophoblast cells. In order to assess this, a single
      dose of 5azaC was injected intraperitoneally into pregnant rats during days 1-19
      of gestation. Animals were euthanised on day 20 and placental weight, as well as
      glycoprotein composition, was analysed together with immunohistological
      assessment of the degree of proliferation of the trophoblast cells. The placental
      weight was found to be significantly smaller in animals treated by 5azaC during
      days 4 to 14 of gestation (p<0.01, Student's t-test). The treatment on days 4, 5,
      and 6 resulted in a lack of labyrinth with the strong proliferative activity of
      the cells in the basal layer. Expression of glycoproteins with molecular mass
      smaller than 60 kDa was reduced with treatment on day 6. The 5azaC administered
      from days 7 to 10 completely disturbed the placental structure and the
      proliferation of trophoblast cells was poor. During these days GP70 exhibited
      stronger expression in treated animals, contrary to GP40, which was stronger in
      controls. A natural border between the labyrinth and the basal layer was
      established on days 11 and 12. The basal layer was dominant with a lower
      proliferation of trophoblast cells compared with the controls. With the
      establishment of the labyrinth on day 13, the expression of GP40 was restored.
      Proliferation of the trophoblast cells from days 13 to 15 was higher compared
      with the controls. The changes in placental mass and the proliferative ability of
      trophoblast cells in rat placenta exposed to 5azaC represent more proof of the
      importance of epigenetics in the regulation of placental development.

PMID- 17509680
TI  - Analysis of cellular calcium fluxes in cardiac muscle to understand calcium
      homeostasis in the heart.
AB  - Central to controlling intracellular calcium concentration ([Ca(2+)](i)) are a
      number of Ca(2+) transporters and channels with the L-type Ca(2+) channel, Na(+)
      Ca(2+) exchanger and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) being of
      particular note in the heart. This review concentrates on the regulation of
      [Ca(2+)](i) in cardiac muscle and the homeostatic mechanisms employed to ensure
      that the heart can operate under steady-state conditions on a beat by beat basis.
      To this end we discuss the relative importance of various sources and sinks of
      Ca(2+) responsible for initiating contraction and relaxation in cardiac myocytes
      and how these can be manipulated to regulate the Ca(2+) content of the major
      Ca(2+) store, the sarcoplasmic reticulum (SR). We will present a simple feedback
      system detailing how such control can be achieved and highlight how small
      perturbations to the steady-state operation of the feedback loop can be both
      beneficial physiologically and underlie changes in systolic Ca(2+) in ageing and
      heart disease. In addition to manipulating the amplitude of the normal systolic
      Ca(2+) transient, the tight regulation of SR Ca(2+) content is also required to
      prevent the abnormal, spontaneous or diastolic release of Ca(2+) from the SR.
      Such diastolic events are a major factor contributing to the genesis of cardiac
      arrhythmias in disease situations and in recently identified familial mutations
      in the SR Ca(2+) release channel (ryanodine receptor, RyR). How such diastolic
      release arises and potential mechanisms for controlling this will be discussed.

PMID- 17509681
TI  - dup(1)(q21q32) as a sole cytogenetic event is associated to a leukemic
      transformation in myelodysplastic syndromes.
AB  - Duplication of the long arm of chromosome 1 (1q) has been detected accompanied
      with other chromosome abnormalities in Myelodysplastic Syndromes (MDS). However,
      as a sole karyotypic change, it is rarely observed. We present here two patients
      affected of a MDS that showed a dup(1)(q21q32) as a sole cytogenetic change in
      their bone marrow cells. Complementary methodologies confirmed the duplication of
      chromosome 1q and, did not show additional cryptic chromosome abnormalities. One
      patient acquired a secondary trisomy 8 and the other one progressed toward an
      acute leukemia with no additional cytogenetic alterations.

PMID- 17509682
TI  - Angiogenesis revisited in CLL.

PMID- 17509683
TI  - A role for Hemolectin in coagulation and immunity in Drosophila melanogaster.
AB  - Hemolectin has been identified as a candidate clotting factor in Drosophila. We
      reassessed the domain structure of Hemolectin (Hml) and propose that instead of C
      type lectin domains, the two discoidin domains are most likely responsible for
      the protein's lectin activity. We also tested Hml's role in coagulation and
      immunity in Drosophila. Here we describe the isolation of a new hml allele in a
      forward screen for coagulation mutants, and our characterization of this and two
      other hml alleles, one of which is a functional null. While loss of Hml had
      strong effects on larval hemolymph coagulation ex vivo, mutant larvae survived
      wounding. Drosophila thus possesses redundant hemostatic mechanisms. We also
      found that loss of Hml in immune-handicapped adults rendered them more sensitive
      to Gram(-) bacterial infection. This demonstrates an immunological role of this
      clotting protein and reinforces the importance of the clot in insect immunity.

PMID- 17509684
TI  - Dissolved organic carbon reduces the toxicity of copper to germlings of the
      macroalgae, Fucus vesiculosus.
AB  - This study investigates the effects of waterborne copper exposure on germling
      growth in chemically defined seawater. Germlings of the macroalgae, Fucus
      vesiculosus were exposed to a range of copper and dissolved organic carbon (DOC
      as humic acid) concentrations over 14 days. Germling growth was found to be a
      sensitive indicator of copper exposure with total copper (TCu) and labile copper
      (LCu) EC(50) values of approximately 40 and 20 microg/L, respectively, in the
      absence of added DOC. The addition of DOC into the exposure media provided
      germlings with protection against copper toxicity, with an increased TCu EC(50)
      value of 117.3 microg/L at a corrected DOC (cDOC from humic acid only)
      concentration of 2.03 mg/L. The LCu EC(50) was not affected by a cDOC
      concentration of 1.65 mg/L or less, suggesting that the LCu concentration not the
      TCu concentration was responsible for inhibiting germling growth. However, at a
      cDOC concentration of approximately 2mg/L an increase in the LCu EC(50) suggests
      that the LCu concentration may play a role in the overall toxicity to the
      germlings. This is contrary to current understanding of aquatic copper toxicity
      and possible explanations for this are discussed.

PMID- 17509685
TI  - The responses of rainbow trout gills to high lithium and potassium concentrations
      in water.
AB  - The objective of this study is to discern the effects of increased waterborne
      lithium and potassium on rainbow trout gill histology, lipid composition, and
      enzyme activity. The study aims to elucidate the effects of these ions in the
      laboratory in concentrations similar to those prevailing in a forest lake
      Poppalijarvi in a contaminated mining area in NW Russia. Under the lithium and
      potassium exposure, the fish were further stressed by high pH (8.2 as in Lake
      Poppalijarvi) and lack of food. These multiple stress conditions altered the gill
      membrane fluidity by increasing sphingomyelin (5.5+/-0.6 compared to 2.9+/-0.3%
      in the control) and reducing cholesterol (4+/-1 compared to 17+/-3 mg g(-1) in
      the control). The total ATPase activity tended to be higher in the lithium
      potassium-exposed group (46+/-6 compared to 34+/-2 micromol Pi h(-1) mg(
      1)protein in the control). Lithium toxicity was lowered here by the protective
      role of higher potassium contents.

PMID- 17509686
TI  - PestScreen: a screening approach for scoring and ranking pesticides by their
      environmental and toxicological concern.
AB  - A chemical ranking and scoring method entitled PestScreen has been developed as a
      screening tool to provide a relative assessment of pesticide hazards to human
      health and the environment. The method was developed to serve as an analytical
      tool in screening and identification of pesticides of environmental concern used
      in agriculture. PestScreen incorporates both the toxic effects of pesticides and
      their fate and exposure characteristics in different compartments of the
      environment. This is done by combining measures of chemical toxicity pertaining
      to both human health and the environment with chemical release amounts and
      information on overall environmental persistence, long-range transport potential
      and human population intake fractions. Each hazard measure is scored and weighted
      and finally combined with the pesticide application dose to provide a single
      final indicator of relative concern (PestScore). Results for 217 pesticides are
      presented and the practical implementation is illustrated on behalf of three
      practical case studies.

PMID- 17509687
TI  - Vitrectomy for the diagnosis and management of uveitis of unknown cause.
AB  - PURPOSE: To determine the diagnostic yield of tests commonly used for vitreous
      fluid analysis in eyes with suspected intraocular infection or malignancy.
      DESIGN: Noncomparative interventional case series. PARTICIPANTS: Forty-four
      consecutive patients (45 eyes) treated from 1998 through 2006 with posterior
      segment inflammation who underwent pars plana vitrectomy for diagnostic purposes.
      INTERVENTION: Vitreous specimens obtained via pars plana vitrectomy were analyzed
      by microbiologic culture, cytologic analysis, and flow cytometry. MAIN OUTCOME
      MEASURES: Diagnostic yield and sensitivity of each test performed on vitreous
      specimens and visual outcomes of eyes that underwent diagnostic vitrectomy (DVx).
      RESULTS: Preoperative diagnoses were infection in 15 eyes and malignancy in 30
      eyes. Overall, vitreous analysis identified a specific cause in 9 (20%) of 45
      eyes. The overall sensitivity of DVx was 63.6%. The sensitivities of individual
      tests were: culture, 50%; cytologic analysis, 66.7%; and flow cytometry, 83.3%.
      The yields of diagnostic tests were: culture, 5.7%; cytologic analysis, 14.3%;
      and flow cytometry, 20.6%. Final diagnoses were infection in 6 eyes, malignancy
      in 9 eyes, and idiopathic in 30 eyes. Mean visual acuity improved significantly
      in the first 6 months after DVx. Visual acuity improved in 60% of eyes, with
      37.8% of eyes improving by 3 lines or more. CONCLUSIONS: Analysis of vitreous
      fluid by widely available tests is useful in identifying intraocular infection or
      malignancy. Most patients experienced a substantial improvement in vision.

PMID- 17509688
TI  - Comparison of the ocular hypotensive efficacy of adjunctive brimonidine 0.15% or
      brinzolamide 1% in combination with travoprost 0.004%.
AB  - PURPOSE: To compare efficacies of adjunctive therapy with brimonidine 0.15% and
      adjunctive therapy with brinzolamide 1% in combination with travoprost 0.004%.
      DESIGN: Three-month randomized, parallel-group, double-masked, multicenter
      clinical trial. PARTICIPANTS: Patients with primary open-angle glaucoma,
      exfoliation glaucoma, or ocular hypertension with intraocular pressure (IOP) > 18
      mmHg on monotherapy with travoprost (N = 163). METHODS: Patients were randomized
      to receive adjunctive therapy with twice-daily brimonidine (N = 79) or twice
      daily brinzolamide (N = 84). Treatment efficacy was assessed after 1 and 3 months
      of combination therapy. Intraocular pressure was measured at 8 am, noon, and 4 pm
      at baseline (on travoprost monotherapy) and after 3 months of combination
      therapy. Mean diurnal IOP was defined as the average of the IOP measurements at
      these 3 time points. Adverse events were recorded at each visit. MAIN OUTCOME
      MEASURE: Difference between treatment groups in mean diurnal IOP at month 3,
      adjusted for difference in baseline IOP, using analysis of covariance. RESULTS:
      Mean diurnal IOPs (+/- standard error of the mean) at baseline were 21.7+/-0.33
      mmHg in the brimonidine group and 21.1+/-0.29 mmHg in the brinzolamide group (P =
      0.16). Mean diurnal IOPs at month 3 were 19.6+/-0.41 mmHg in the brimonidine
      group and 18.4+/-0.33 mm Hg in the brinzolamide group (P = 0.019). At month 3,
      mean diurnal IOPs, adjusted for difference in baseline IOP, were 19.3+/-0.27 in
      the brimonidine group and 18.6+/-0.25 in the brinzolamide group (P = 0.035).
      CONCLUSIONS: The combination of travoprost and brinzolamide was statistically
      significantly more efficacious than the combination of travoprost and brimonidine
      in lowering IOP. The clinical significance of this difference is uncertain.

PMID- 17509689
TI  - Pegaptanib 1-year systemic safety results from a safety-pharmacokinetic trial in
      patients with neovascular age-related macular degeneration.
AB  - OBJECTIVE: To characterize the safety, tolerability, and pharmacokinetics of the
      pegylated anti-vascular endothelial growth factor (VEGF) aptamer pegaptanib
      sodium in subfoveal choroidal neovascularization secondary to age-related macular
      degeneration (AMD). DESIGN: Prospective 2-cohort study: (1) open-label cohort and
      (2) randomized, double-masked, uncontrolled multicenter trial. PARTICIPANTS: In
      the combined cohorts, 147 subjects with any angiographic subtype of subfoveal
      choroidal neovascularization secondary to AMD and best-corrected visual acuities
      (VAs) in the study eye of 20/40 to 20/320 and in the fellow eye of 20/800 or
      better received pegaptanib sodium. INTERVENTION: Subjects were randomized to
      receive intravitreous pegaptanib sodium (1 mg or 3 mg [3- and 10-fold higher than
      the 0.3-mg approved dose]) every 6 weeks for 54 weeks. MAIN OUTCOME MEASURES:
      Safety assessments included blood chemistries, urinalyses, vital signs,
      electrocardiograms, serum antipegaptanib antibody assays, adverse events, VAs,
      and intraocular pressures. After the first, fourth, and eighth injections, serial
      blood samples were obtained for quantification of pegaptanib plasma
      concentrations. RESULTS: No antipegaptanib immunoglobulin G (IgG) or IgM
      antibodies were detected. Few systemic adverse events were noted. Mild or
      moderate ocular adverse events related to the injection procedure were reported
      in most patients. Pegaptanib did not accumulate in plasma after multiple doses;
      systemic exposures were similar after the first, fourth, and eighth doses. The
      mean apparent terminal half-life was 10 days. Evaluation of blood pressure (BP)
      and urine protein, both of which are known to be affected by systemic VEGF
      inhibition, indicated no evidence of a pegaptanib treatment effect on these
      parameters. Mean BP at the end of year 1 remained below 140 mmHg (systolic) and
      90 mmHg (diastolic), levels considered hypertension by the American College of
      Cardiology. CONCLUSIONS: At doses up to 10-fold higher than the 0.3-mg dose
      approved for the treatment of AMD, pegaptanib sodium was well tolerated, with no
      detectable clinical evidence of systemic VEGF inhibition (i.e., no clinically
      meaningful changes in proteinuria or mean BP) and no clinically relevant ocular
      inflammation. Most ocular adverse events were related to the injection procedure
      itself and were mild or moderate in severity.

PMID- 17509690
TI  - The microglial networks of the brain and their role in neuronal network
      plasticity after lesion.
AB  - Microglia are the resident inflammatory cells of the central nervous system (CNS)
      extending a network of processes in the CNS parenchyma. Following axon lesion to
      neurons, most extensively studied in motoneurons, there is a typical retrograde
      response at the cell body level, including the removal or 'stripping' of synapses
      from the perikaryon and dendrites of affected cells. Microglia have been
      attributed a main and active role in this process, although also an involvement
      of activated astrocytes has been suggested. The signaling pathways for this
      'synaptic stripping' have so far been unknown, but recently some classical immune
      recognition molecules, the MHC class I molecules, have been shown to have a
      strong influence on the strength and pattern of the synapse elimination response.
      Since there is an expression of MHC class I in both neurons and glia, in
      particular microglia, as well as MHC class I related receptors in axons and
      microglia, there are good reasons to believe that classical immune recognition
      signaling between neurons and glia underlies part of the 'stripping' response. A
      role for microglia in an interplay with synapses based on this type of signaling
      is further exemplified by the fact that, in the absence of some MHC class I
      related receptors normally found on microglia during development, profound
      effects on synaptic function and biochemistry have been demonstrated. Such
      effects may be linked to the development of various disorders of the CNS, such as
      degenerative disease.

PMID- 17509691
TI  - Kisspeptin signalling in the brain: steroid regulation in the rodent and ewe.
AB  - The Kiss1 gene encodes a family of peptides called kisspeptins, which are the
      natural ligands for the receptor GPR54. In humans and mice, inactivating
      mutations of GPR54 results in hypogonadotropic hypogonadism, indicating that
      kisspeptins play a vital role in the regulation of GnRH secretion. In many
      species, centrally administered kisspeptins stimulate gonadotrophin secretion in
      a GnRH-dependant manner. Moreover, virtually all GnRH neurons coexpress GPR54. In
      the hypothalamus, the vast majority of kisspeptin producing cells also express
      sex steroid receptors, particularly estrogen receptor alpha. Thus, sex steroids
      are able to directly regulate the expression of Kiss1 mRNA, implicating
      kisspeptins as the 'missing link' between sex steroid feedback and GnRH
      secretion. Kiss1-expressing cells are localised to various regions of the
      forebrain in rodents, primates and sheep. In the arcuate nucleus (ARC) of the
      rodent and the ewe, sex steroids inhibit the expression of Kiss1 mRNA, suggesting
      that the kisspeptin secreting neurons here are the conduit for the negative
      feedback regulation of GnRH secretion. However, in the rodent anteroventral
      periventricular nucleus (AVPV), sex steroids induce the expression of Kiss1,
      implying that these kisspeptin neurons play a role in the positive feedback
      regulation of GnRH secretion. In sheep, there are no Kiss1 neurons in the AVPV
      and Kiss1 mRNA expression in the ARC is stimulated immediately prior to the
      preovulatory GnRH/luteinising hormone surge. Thus, kisspeptin neurons in the ARC
      of the ewe appear well placed to play a role in the negative and positive
      feedback regulation of GnRH exerted by sex steroids.

PMID- 17509692
TI  - Correlative morphometric and electrochemical measurements of serotonin content in
      earthworm muscles.
AB  - Distribution of serotonin (5-HT) content of nervous fibers in both the somatic
      and the visceral muscle of Eisenia fetida have been investigated using
      immunocytochemical staining and voltammetric measurements. The somatic muscles in
      the body wall are richer innervated with serotoninergic fibers than the visceral
      ones in the pharynx and gizzard. The relative density of immunopositive fibers in
      the circular muscle layer of the body wall was found to be 2.73% while in the
      prostomium it was 1.02%. In the case of the muscle in pharynx 1.12% and in
      gizzard 1.28% density values were found. Differential Pulse Voltammetric (DPV)
      measurements with carbon fiber electrodes in the above mentioned muscle layers
      gave 272.5 nA, 135.0 nA, 122.5 nA, 137.5 nA peak heights, respectively. In the
      statistical analysis T-test was used at a confidence level of 95% (p<0.05). DPV
      current peak (i(p)) values reflect clearly the 5-HT concentration differences.
      Significant correlation was found between the innervation density and the i(p)
      values recorded in different areas. The i(p) values recorded at different times
      in different locations are determined by instantaneous serotonin concentration of
      the living tissue. As far as we know this is the first report using in vivo
      voltammetry investigating serotonin content in earthworm, E. fetida.

PMID- 17509693
TI  - Assessing the preventive effects of cognitive therapy following relief of
      depression: A methodological innovation.
AB  - BACKGROUND: Strategies to compute benefits from continuing cognitive therapy for
      patients with recurrent major depression do not take into account whether
      discontinuing treatments may induce temporary increases in the risk that symptoms
      return (discontinuation-effect). METHODS: We apply varying-effects analyses and
      compare findings with traditional methods to assess the effects of continuation
      phase cognitive therapy. Two years of data came from 79 patients with recurrent
      major depression who responded to acute cognitive therapy. Patients were
      randomized to either an experimental cohort (n=39) who received 10-session,
      protocol continuation-phase therapy for 8 months, or a control cohort (n=40) who
      stopped protocol treatment after the acute-phase. Symptoms were assessed using
      the Longitudinal Interval Follow-up Evaluation (LIFE). Symptom risk rates were
      computed weekly by cohort as the proportion of patients at risk who were
      suffering from a major depressive episode. RESULTS: Significant discontinuation
      effects occurred when protocol treatments stopped for both experimental and
      control cohorts. Following acute-phase care, traditional computation methods
      (week 1-35) revealed treated patients had 18% of the risk for symptoms as
      controls. Expanding the observation period (week 1-74) to include these
      discontinuation-effects revealed more modest initial effect sizes (43%), but
      significant long-term effects (54% for week 75-101). LIMITATIONS: Limitations
      include limited sample size, one-site study, confounds from patient-level
      interactions, and off-protocol use of depression-related care. CONCLUSIONS:
      Varying-effects analyses can describe how outcomes from cognitive therapy may
      unfold over time for patients with major depression. These analyses reveal
      complex longitudinal patterns that otherwise are not detectable with traditional
      time-to-event methods. Specifically, we observed discontinuation-effects, or
      temporary spikes in symptom risks that occur after treatment ends. Further
      research is needed to identify the mechanisms driving these effects. Future
      studies are needed to determine if higher risks result from the patients' anxiety
      as they attempt to maintain gains independent of ongoing therapy, or reflect
      residual symptoms previously suppressed by treatment. We also observed longer
      term preventive effects from therapy. Again, further research is recommended to
      determine the extent to which lower risks result from coping and compensatory
      skills learned during cognitive therapy. These findings suggest that varying
      effects analyses may provide an appealing paradigm for understanding treatment
      related effects in episodic illness.

PMID- 17509694
TI  - Patient education and group counselling to improve the treatment of depression in
      primary care: a randomized controlled trial.
AB  - BACKGROUND: The Contactus program for depressed patients in primary care,
      consists of six lectures about depression, each followed by a group discussion.
      The aim of this study was to investigate if Contactus can improve treatment
      outcome in comparison to a control group. METHODS: Forty-six primary care centres
      in Sweden, each randomly allocated either to the Contactus group or to the
      control group, included depressed patients, 205 in the Contactus group and 114 in
      the control group. Besides regular treatment of depression, the Contactus group
      participated in the educational program. At start and after 6 weeks, patients
      filled in a questionnaire and the self-reports: HADS (Hospital Anxiety and
      Depression Scale) and GAF-self (Global Assessment of Functioning). RESULTS: After
      6 weeks, clinically depressed patients (HAD-depression score >10) had a mean
      improvement in HAD-D of 4.6 in Contactus vs. 3.0 in controls (p=0.02), and 72%
      vs. 47% considered themselves to feel better (p=0.01). Increase in GAF score was
      11.8 vs. 5.8 (p=0.04), respectively. According to HADS, 55% in Contactus were
      responders vs. 29% among controls (p=0.006), and 42% vs. 21% (p=0.02) were in
      remission. LIMITATIONS: Only 40% of the patients in Contactus and 35% among
      controls were clinically depressed according to the HADS (>10 points) at
      inclusion. CONCLUSIONS: Patient education and group counselling contributes
      significantly to better improvement among depressed patients. Group treatment is
      inexpensive and could be implemented in the routine care of depressed patients in
      primary care.

PMID- 17509695
TI  - Healthcare and preventive services utilization of elderly Europeans with
      depressive symptoms.
AB  - BACKGROUND: Depressive symptoms are associated with increased healthcare
      utilization. However, it is unclear whether depressed individuals experience more
      or less frequent access to preventive services. Our goal was to investigate the
      association between depressive symptoms and both utilization of healthcare and
      preventive services. METHODS: Baseline self-reported data (2004) from non
      institutionalized individuals aged > or =50 years participating in the Survey of
      Health, Ageing, and Retirement in Europe (SHARE) were used. Of the 18,560
      respondents to the baseline questionnaire, 13,580 answered the supplementary
      questionnaire, which included measures of preventive services. Healthcare
      utilization during the previous 12 months, including outpatient visits,
      medication, hospitalization, surgery, and home healthcare were assessed.
      Preventive service measures assessed the participation in influenza immunization
      and colorectal and breast cancer screening. Depression status was assessed with
      the EURO-D, a validated instrument for which a score >3 defines clinically
      significant depressive symptoms. Logistic regressions were performed adjusting
      for age, gender, socioeconomic status, behavioral risk, chronic disease,
      disability, and country of residence. RESULTS: The estimated prevalence of
      depressive symptoms was 28.2%. Depressive symptoms were associated with
      significantly greater use of all healthcare domains but not preventive services,
      with the exception of colorectal cancer screening. Similar trends were found for
      each country of residence and for both genders. LIMITATIONS: It was not known
      whether medical tests were used for screening or diagnostic purposes.
      CONCLUSIONS: SHARE data suggest that patients with depressive symptoms are
      frequent users of healthcare but not preventive services. Low screening rates may
      reflect missed screening opportunities rather than a lack of screening
      opportunities.

PMID- 17509696
TI  - WITHDRAWN: Membranous glomerulonephritis in the Iberian Lynx (Lynx pardinus).
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17509697
TI  - Cancer chemotherapy impairs contextual but not cue-specific fear memory.
AB  - This study examined the effects of a standard breast cancer chemotherapeutic
      protocol on learning and memory in rats. Ovariectomized rats were treated once a
      week for 3 weeks with a combination of cyclophosphamide and doxorubicin prior to
      training in a classical fear conditioning task. Training took place 1 week after
      the final treatment. During the training session, an auditory stimulus (a tone)
      was paired with a mild foot-shock. The resulting conditioned fear to the tone
      (cue-specific fear) and to the training environment (contextual fear) was
      measured in subsequent test sessions. Chemotherapy did not affect the acquisition
      of the conditioned response (freezing) during the training session or the
      expression of fear during the tone test session. In contrast, rats treated with
      cyclophosphamide and doxorubicin exhibited decreased freezing during the context
      test session, suggestive of a specific deficit in hippocampal-related learning
      and memory. Together, these data indicate that administration of cyclophosphamide
      and doxorubicin may have toxic effects on the hippocampus and results in specific
      learning deficits shortly after treatment has ended.

PMID- 17509698
TI  - Characterisation of exogenous folate transport in Plasmodium falciparum.
AB  - Folate salvage by Plasmodium falciparum is an important source of key cofactors,
      but little is known about the underlying mechanism. Using synchronised parasite
      cultures, we observed that uptake of this dianionic species against the negative
      inward electrochemical gradient is highly dependent upon cell-cycle stage,
      temperature and pH, but not on mono- or divalent metal ions. Energy dependence
      was tested with different sugars; glucose was necessary for folate import,
      although fructose was also able to function in this role, unlike sugars that
      cannot be processed through the glycolytic pathway. Import into both infected
      erythrocytes and free parasites was strongly inhibited by the anion-channel
      blockers probenecid and furosemide, which are likely to be acting predominantly
      on specific folate transporters in both cases. Import was not affected by high
      concentrations of the antifolate drugs pyrimethamine and sulfadoxine, but was
      inhibited by the close folate analogue methotrexate. The pH optimum for folate
      uptake into infected erythrocytes was 6.5-7.0. Dinitrophenol and nigericin, which
      strongly facilitate the equilibration of H(+) ions across biological membranes
      and thus abolish or substantially reduce the proton gradient, inhibited folate
      uptake profoundly. The ATPase inhibitor concanamycin A also greatly reduced
      folate uptake, further demonstrating a link to ATP-powered proton transport.
      These data strongly suggest that the principal folate uptake pathway in P.
      falciparum is specific, highly regulated, dependent upon the proton gradient
      across the parasite plasma membrane, and is likely to be mediated by one or more
      proton symporters.

PMID- 17509699
TI  - Aqueous peroxyl radical exposure to THP-1 cells causes glutathione loss followed
      by protein oxidation and cell death without increased caspase-3 activity.
AB  - Protein oxidation within cells exposed to oxidative free radicals has been
      reported to occur in an uninhibited manner with both hydroxyl and peroxyl
      radicals. In contrast, THP-1 cells exposed to peroxyl radicals (ROO(*)) generated
      by thermo decomposition of the azo compound AAPH showed a distinct lag phase of
      at least 6 h, during which time no protein oxidation or cell death was observed.
      Glutathione appears to be the source of the lag phase as cellular levels were
      observed to rapidly decrease during this period. Removal of glutathione with
      buthionine sulfoxamine eliminated the lag phase. At the end of the lag phase
      there was a rapid loss of cellular MTT reducing activity and the appearance of
      large numbers of propidium iodide/annexin-V staining necrotic cells with only 10%
      of the cells appearing apoptotic (annexin-V staining only). Cytochrome c was
      released into the cytoplasm after 12 h of incubation but no increase in caspase-3
      activity was found at any time points. We propose that the rapid loss of
      glutathione caused by the AAPH peroxyl radicals resulted in the loss of caspase
      activity and the initiation of protein oxidation. The lack of caspase-3 activity
      appears to have caused the cells to undergo necrosis in response to protein
      oxidation and other cellular damage.

PMID- 17509700
TI  - OCTN2VT, a splice variant of OCTN2, does not transport carnitine because of the
      retention in the endoplasmic reticulum caused by insertion of 24 amino acids in
      the first extracellular loop of OCTN2.
AB  - A novel organic cation transporter OCTN2 is indispensable for carnitine transport
      across plasma membrane and subsequent fatty acid metabolism in the mitochondria.
      Here, we report a novel splice variant of OCTN2 (OCTN2VT), in which a 72-base
      pair sequence located in the first intron of OCTN2 gene was spliced between exons
      1 and 2 of OCTN2, causing the insertion of 24 amino acids in the first
      extracellular loop of OCTN2. Despite the similarity between OCTN2 and OCTN2VT
      regarding primary structure and tissue distribution, their biochemical
      characteristics were significantly different. OCTN2 was expressed on the plasma
      membrane with robust N-glycosylation, whereas OCTN2VT was retained in the
      endoplasmic reticulum (ER) with poor N-glycosylation. In addition, the retention
      in the ER caused no carnitine uptake into the cells. These results demonstrate
      that the biochemical and functional characteristics of OCTN2VT are distinct from
      OCTN2 due to the insertion of 24 amino acids in the first extracellular loop.

PMID- 17509701
TI  - MUC1 is involved in trophoblast transendothelial migration.
AB  - The factors that regulate trophoblast invasion of the uterine vasculature are
      incompletely understood. In this paper we show that macaque trophoblasts express
      the mucin, MUC1, and that it is involved in trophoblast-endothelial interaction.
      Immunocytochemistry, Western blotting and RT-PCR analyses confirmed that MUC1 was
      expressed by isolated early gestation macaque trophoblasts. MUC1 was also
      detected in endovascular trophoblasts in sections of placental-decidual tissue
      during early gestation. A blocking antibody against MUC1 reduced trophoblast
      adhesion to uterine endothelial cells and also blocked trophoblast
      transendothelial migration. MUC1 is known to bind to Intercellular Adhesion
      Molecule-1 (ICAM-1) in other systems. Incubation in the presence of a blocking
      antibody against Intercellular Adhesion Molecule-1 (ICAM-1) or recombinant ICAM-1
      modestly, but significantly, reduced transendothelial trophoblast migration.
      These results are consistent with the idea that MUC1 is involved in trophoblast
      adhesion to uterine endothelial cells and in trophoblast transendothelial
      migration.

PMID- 17509702
TI  - Changes in QT dispersion after thrombolysis for stroke.
AB  - BACKGROUND: QT dispersion (QTD) reflects heterogeneity of myocardial
      repolarization, which is modulated by the central nervous system. Although
      largely studied in patients with cardiovascular disease, QTD is increased in
      acute stroke and this finding is an independent predictor of functional outcome
      and mortality following acute neurological events. HYPOTHESIS: The hypothesis of
      this study was to determine whether changes in QTD in patients presenting with
      ischemic stroke parallel changes in neurologic function. METHODS: We
      retrospectively studied 30 consecutive patients (76+/-9 years, 50% male) who
      received thrombolytic therapy for acute ischemic stroke between September 1996
      and August 2002, and had multiple electrocardiograms (ECGs). QTD was calculated
      from the admission ECG and the last available ECG (median 3 days) during hospital
      admission as the absolute difference between the maximum and minimum QT intervals
      in at least 11 of 12 leads. The National Institute of Health Stroke Scale (NIHSS)
      was used to assess neurological status on admission and discharge. DeltaQTD was
      calculated as the absolute difference between QTD measured on admission and on
      the last available ECG. Absolute changes in heart rate corrected QTD (DeltaQTDc)
      and NIHSS scores (DeltaNIHSS) were also calculated. RESULTS: DeltaQTD was
      significantly higher in the 27% of patients who died as compared to the survivors
      (44+/-26 ms vs. -2+/-21 ms, p<.001). DeltaNIHSS correlated directly with DeltaQTD
      (r=0.57, p<0.001) and with DeltaQTDc (r=0.60, p<0.001). The NIHSS score changed
      in the same direction 3.1 units (95% CI: 2.0, 4.2) for every 10 ms change in QTD.
      CONCLUSION: DeltaQTD are associated with changes in neurological function in
      patients treated with thrombolytic therapy for acute ischemic stroke.

PMID- 17509703
TI  - Negative stress echo: further prognostic stratification with assessment of
      pressure-volume relation.
AB  - BACKGROUND: A maximal negative stress echo identifies a low risk for subsequent
      hard events subset. However, the potentially prognostically relevant information
      on global contractile reserve on the left ventricle is missed by standard
      regional wall motion assessment, and can be obtained by end-systolic pressure
      volume relationship (PVR) evaluation. AIM: To assess the relative prognostic
      value of PVR in patients with negative stress echo. METHODS: We enrolled 99
      consecutive patients (age=61+/-14 years; 81 males, LVEF 47+/-14%, WMSI=1.42+/
      0.50) with negative exercise stress echo for standard wall motion criteria. To
      build the PVR, the force was determined at rest and peak stress as the ratio of
      the systolic pressure/end-systolic volume index. All patients were followed-up on
      medical therapy. RESULTS: Median follow-up was 21 months (interquartile range 12
      26). Twenty-nine events have been observed: 6 deaths, 10 heart failure related
      hospitalization and 13 worsening NYHA class of >or=1 grade. Using Cox's
      proportional hazard model the best independent predictor of total events was
      SP/ESV index change (rest-stress) <1.5 mm Hg/ml/m(2) as determined by ROC
      analysis cut-off (RR=29, p=0.001, sensitivity=80%, specificity=93%). The overall
      survival and event-free survival was 34% in patients with change (rest-stress)
      SP/ESV index<1.5 mm Hg/ml/m(2) and 97% in whose with >1.5 mm Hg/ml/m(2).
      CONCLUSIONS: In patients with negative stress echo, a preserved global
      contractility response can be easily identified through stress-induced variation
      in SP/ESV index, with powerful further risk stratification.

PMID- 17509704
TI  - The effects of losartan on signal-averaged P wave in patients with atrial
      fibrillation.
AB  - BACKGROUND: Losartan has recently been reported to suppress atrial structural
      remodeling. However, few reports exist on signal-averaged electrocardiography
      (ECG) for preventing atrial electrical remodeling. We examined the effect of
      losartan on atrial electricity by using signal-averaged ECG of P waves. METHODS:
      The subjects comprised 40 patients with essential hypertension complicated with
      symptomatic paroxysmal atrial fibrillation. The patients received pilsicainide
      for the complication; they were defibrillated and divided into two subgroups for
      antihypertensive therapy: calcium antagonist-administrated (CB) and losartan
      administrated (LOS) groups. We recorded the signal-averaged electrocardiography
      of P waves and calculated (1) filtered P wave duration (PD), (2) the voltage
      integral for the entire P wave (integral-p), and (3) the root mean square
      voltages of the terminal 40, 30, and 20 ms (RMS-40, RMS-30, and RMS-20).
      Procollagen C propeptide type I (PIP) and A- and B-type natriuretic peptide (ANP
      and BNP, respectively) levels in the groups were measured before and after
      antihypertensive agent administration. RESULTS: RMS-20 increased significantly
      and PD decreased significantly in the LOS group 24 weeks after antihypertensive
      drug administration; however, they remained unchanged in the CB group. Integral-p
      decreased significantly in both groups, and the decrease rate was significantly
      higher in the LOS group. Serum BNP levels decreased significantly only in the LOS
      group. CONCLUSIONS: Losartan inhibits atrial remodeling by inhibiting left atrial
      fibrosis as indicated by the procollagen C propeptide type I, ANP, and BNP
      levels. Signal-averaged ECG demonstrated that losartan suppresses atrial
      fibrillation recurrence by improving atrial conduction disturbance.

PMID- 17509705
TI  - Application of portfolio theory to risk-based allocation of surveillance
      resources in animal populations.
AB  - Distribution of finite levels of resources between multiple competing tasks can
      be a challenging problem. Resources need to be distributed across time periods
      and geographic locations to increase the probability of detection of a disease
      incursion or significant change in disease pattern. Efforts should focus
      primarily on areas and populations where risk factors for a given disease reach
      relatively high levels. In order to target resources into these areas, the
      overall risk level can be evaluated periodically across locations to create a
      dynamic national risk landscape. Methods are described to integrate the levels of
      various risk factors into an overall risk score for each area, to account for the
      certainty or variability around those measures and then to allocate surveillance
      resources across this risk landscape. In addition to targeting resources into
      high risk areas, surveillance continues in lower risk areas where there is a
      small yet positive chance of disease occurrence. In this paper we describe the
      application of portfolio theory concepts, routinely used in finance, to design
      surveillance portfolios for a series of examples. The appropriate level of
      resource investment is chosen for each disease or geographical area and time
      period given the degree of disease risk and uncertainty present.

PMID- 17509706
TI  - Modeling of the inactivation of Salmonella typhimurium by supercritical carbon
      dioxide in physiological saline and phosphate-buffered saline.
AB  - In this study, we used supercritical carbon dioxide (SC-CO(2)) to inactivate
      Salmonella typhimurium suspended in physiological saline (PS) or phosphate
      buffered saline (PBS). The colony forming activity of S. typhimurium was
      completely lost (i.e., 8-log reduction) under the following condition ranges:
      pressures of 80-150 bar, temperatures of 35-45 degrees C and 10-50 min treatment
      times. The microbial inactivation process had three distinct phases and was
      modeled by the modified Gompertz model. Generally, an increase in pressure at
      constant temperature, and an increase in temperature at a constant pressure, both
      enhanced S. typhimurium inactivation. When the cells were suspended in PBS rather
      than PS, the length of time for the complete inactivation significantly
      increased. We observed the surface and internal morphological changes of the
      cells by SEM and TEM, respectively. The extraction of proteinous substances,
      nucleic acids and outer membrane proteins into the suspension during SC-CO(2)
      treatment was also observed. Through SDS-PAGE analysis of the total proteins and
      major outer membrane proteins (OMPs) of SC-CO(2)-treated cells, we found that a
      substantial amount of the total soluble proteins had converted into insoluble
      protein.

PMID- 17509707
TI  - A small-scale method for quantitation of carotenoids in bacteria and yeasts.
AB  - Microbial carotenoids are difficult to extract because of their embedding into a
      compact matrix and prominent sensitivity to degradation. Especially for
      carotenoid analysis of bacteria and yeasts, there is lack of information about
      capability, precision and recovery of the method used. Accordingly, we
      investigated feasibility, throughput and validity of a new small-scale method
      using Micrococcus luteus and Rhodotorula glutinis for testing purposes. For
      disintegration and extraction, we combined primarily mild techniques:
      enzymatically we used combinations of lysozyme and lipase for bacteria as well as
      lyticase and lipase for yeasts. Additional mechanical treatment included
      sonication and freeze-thawing cycles. Chemical treatment with dimethylsulfoxide
      was applied for yeasts only. For extraction we used a methanol-chloroform mixture
      stabilized efficiently with butylated hydroxytoluene and alpha-tocopherol.
      Separation of compounds was achieved with HPLC, applying a binary methanol/tert
      butyl methyl ether gradient on a polymer reversed C30 phase. Substances of
      interest were detected and identified applying a photodiode-array (PDA) and
      carotenoids quantitated as all-trans-beta-carotene equivalents. For evaluation of
      recovery and reproducibility of the extraction method, we used beta-8'-apo
      carotenal as internal standard. The method provides a sensitive tool for the
      determination of carotenoids from bacteria and yeasts and also for small changes
      in carotenoid spectrum of a single species. Corequisite large experiments are
      facilitated by the high throughput of the method.

PMID- 17509708
TI  - Feature extraction via KPCA for classification of gait patterns.
AB  - Automated recognition of gait pattern change is important in medical diagnostics
      as well as in the early identification of at-risk gait in the elderly. We
      evaluated the use of Kernel-based Principal Component Analysis (KPCA) to extract
      more gait features (i.e., to obtain more significant amounts of information about
      human movement) and thus to improve the classification of gait patterns. 3D gait
      data of 24 young and 24 elderly participants were acquired using an OPTOTRAK 3020
      motion analysis system during normal walking, and a total of 36 gait spatio
      temporal and kinematic variables were extracted from the recorded data. KPCA was
      used first for nonlinear feature extraction to then evaluate its effect on a
      subsequent classification in combination with learning algorithms such as support
      vector machines (SVMs). Cross-validation test results indicated that the proposed
      technique could allow spreading the information about the gait's kinematic
      structure into more nonlinear principal components, thus providing additional
      discriminatory information for the improvement of gait classification
      performance. The feature extraction ability of KPCA was affected slightly with
      different kernel functions as polynomial and radial basis function. The
      combination of KPCA and SVM could identify young-elderly gait patterns with 91%
      accuracy, resulting in a markedly improved performance compared to the
      combination of PCA and SVM. These results suggest that nonlinear feature
      extraction by KPCA improves the classification of young-elderly gait patterns,
      and holds considerable potential for future applications in direct dimensionality
      reduction and interpretation of multiple gait signals.

PMID- 17509709
TI  - Developmental coordination disorder: exploration of a cerebellar hypothesis.
AB  - This study explored the hypothesis of a specific cerebellar dysfunction in
      children with developmental coordination disorder (DCD): motor adaptation. The
      performance of a group of children with DCD (3 girls and 6 boys) was compared to
      that of a control group (5 girls and 6 boys) on a measure of motor adaptation,
      the prism adaptation test (PAT). Children were between 6 years 11 months and 11
      years 10 months of age. Between-group differences were only found for PAT
      variables related to throwing accuracy, the DCD group being more variable and
      less accurate than the control group. While no between-group differences were
      found for the adaptation variables, individual data analysis revealed that only
      three children in the DCD group obtained normal adaptation variables. While these
      findings do not confirm the hypothesis of a cerebellar dysfunction, they also do
      not refute it. It is possible that the poor throwing accuracy of the DCD group
      masked the findings for some of the PAT variables. Further exploration of the
      function of the cerebellum among children with DCD is needed.

PMID- 17509710
TI  - Coordination of rapid stepping with arm pointing: anticipatory changes and step
      adaptation.
AB  - The present study explored whether rapid stepping is influenced by the
      coordination of an arm pointing task. Nine participants were instructed to (a)
      point the index finger of the dominant arm towards a target from the standing
      posture, (b) initiate a rapid forward step with the contralateral leg, and (c)
      synchronize stepping and pointing (combined task). Force plate and ankle muscle
      electromyography (EMG) recordings were contrasted between (b) and (c). In the
      combined task, the arm acceleration trace most often peaked around foot-off,
      coinciding with a 15% increase in the forward acceleration of the center of
      gravity (CoG). Backward displacement of the center of foot pressure at foot-off,
      duration of anticipatory postural adjustments (APAs) and ankle muscle EMG
      activity remained unchanged. In contrast, durations of swing phase and whole step
      were reduced and step length was smaller in the combined task. A reduction in the
      swing phase was correlated with an increased CoG forward acceleration at foot
      off. Changes in the biomechanics of step initiation during the combined task
      might be ascribed to the postural dynamics elicited by arm pointing, and not to a
      modulation of the step APAs programming.

PMID- 17509711
TI  - How are Strouhal number, drag, and efficiency adjusted in high level underwater
      monofin-swimming?
AB  - Strouhal number (St) corresponds to a wake parameter based on the tail kinematics
      of swimming animals according to St=A.f/U, where f is the stroke frequency, A is
      the fin-beat peak-to-peak amplitude, and U is the forward speed. St number is a
      trade-off between amplitude and frequency that generates a forward velocity. This
      parameter may therefore be affected by swimming technique, which can be evaluated
      through active drag (AD) and Froude efficiency (eta(F)). The aim of our study was
      therefore to (1) investigate the range of AD and eta(F) values for high level
      monofin-swimmers, (2) explore the range of St numbers, and (3) examine to what
      extent this latter non-dimensional parameter may affect AD and eta(F). To this
      end, experiments have been conducted on 12 international level monofin-swimmers.
      St number, eta(F) (calculated according to the elongated-body theory), and AD
      (computed with velocity perturbation method) were calculated at the same time for
      an underwater fin-swimming trial, at maximal speed. Lowest values of St numbers
      (St=0.34) corresponded to fin-swimmers with highest velocities (R=-.77, p<.05),
      highest efficiencies (R=-.86, p<.001), and lowest active drag (R=.91, p<.001). On
      the one hand, AD was increased with vertical motion of the fin (R=.84, p<.001),
      which increased cross-sectional area (R=.78, p<.05). On the other hand,
      efficiencies showed a tendency to peak at eta(F)=0.82 in a narrow range of St
      numbers close to 0.4. This St range corresponded to the upper limit of the 0.25
      0.4 range usually claimed for maximum efficiency of marine and flying animals.
      Such results suggest that increasing efficiency and reducing drag improves
      performance per se (regardless how these parameters are related with St number).

PMID- 17509712
TI  - Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal
      antibody.
AB  - Targeting drugs to their sites of action is still a major challenge in
      pharmaceutical research. In this study, polylactic-co-glycolic acid (PLGA) immuno
      nanoparticles were prepared for targeting invasive epithelial breast tumour
      cells. Monoclonal antibody (mAb) was used as a homing ligand and was attached to
      the nanoparticle surface either covalently or non-covalently. The presence of mAb
      on the nanoparticle surface, its stability and recognition properties were
      tested. Protein assay, surface plasmon resonance, flow cytometry and fluorescence
      immunostaining confirmed the presence of mAb on nanoparticles in both cases.
      However, a binding assay using cell lysate revealed that the recognition
      properties were preserved only for nanoparticles with adsorbed mAb. These
      nanoparticles were more likely to be bound to the targeted cells than non-coated
      nanoparticles. Both types of nanoparticles entered the target MCF-10A neoT cells
      in mono-culture. In co-culture of MCF-10A neoT and Caco-2 cells immuno
      nanoparticles were localized solely to MCF-10A neoT cells, whereas non-coated
      nanoparticles were distributed randomly. Immuno-nanoparticles entered only MCF
      10A neoT cells, while non-coated nanoparticles were taken up by both cell types,
      indicating specific targeting of the immuno-nanoparticles. In conclusion, we
      demonstrate a method by which mAbs can be bound to nanoparticles without
      detriment to their targeting ability. Furthermore, the results show the
      effectiveness of the new carrier system for targeted delivery of small or large
      active substances into cells or tissues of interest.

PMID- 17509714
TI  - Long-circulating liposome-encapsulated ganciclovir enhances the efficacy of HSV
      TK suicide gene therapy.
AB  - To enhance the efficacy of ganciclovir/herpes simplex virus thymidine kinase
      (GCV/HSV-TK) suicide gene therapy for nasopharyngeal cancer KB, we developed long
      circulating liposome-encapsulated GCV, and evaluated cytotoxicity in vitro and in
      vivo. PEGylated liposome-encapsulated GCV (PEG-GCV-lipo) was prepared by the
      freeze-thawing method. In vitro experiments demonstrated that GCV from liposomes
      was gradually released over a period of 3 days. The in vitro cytotoxicity of PEG
      GCV-lipo was similar to that of GCV solution in human cervical carcinoma HeLa
      cells expressing HSV-TK. Pharmacokinetics studies in mice showed that, compared
      with GCV solution, intravenous and intraperitoneal injection of PEG-GCV-lipo (10
      mg/kg) led to long circulation in plasma; the area under the curve was 36-fold or
      32-fold higher than that of GCV solution, respectively. In GCV/HSV-TK suicide
      gene therapy, the HSV-TK gene complexed with nanoparticle vector was directly
      injected into KB xenografts, and PEG-GCV-lipo or GCV solution was injected
      intravenously in mice once a day (25 mg/kg/day every 2nd day, 4 times). PEG-GCV
      lipo was significantly 3-fold more effective than GCV solution in inhibiting
      tumor growth and produced durable complete tumor remissions on day 11 after
      injection. These findings demonstrate that long-circulating liposome-encapsulated
      GCV is a new approach to drug carriers to enhance the efficacy of suicide gene
      therapy.

PMID- 17509713
TI  - Formulations of biodegradable Nanogel carriers with 5'-triphosphates of
      nucleoside analogs that display a reduced cytotoxicity and enhanced drug
      activity.
AB  - Therapies including nucleoside analogs are associated with severe toxic side
      effects and acquirement of drug resistance. We have previously reported the drug
      delivery in the form of 5'-triphosphates (NTP) encapsulated in cross-linked
      cationic networks of polyethylenimine (PEI) and PEG/Pluronic polymers (Nanogels).
      In this study, Nanogels, containing biodegradable PEI that could easily
      dissociate in reducing cytosolic environment and form products with minimal
      toxicity, were synthesized and displayed low cytotoxicity. Toxicity of Nanogels
      was clearly dependent on the total positive charge of carriers and was 5-6 fold
      lower for carriers loaded with NTP. Though intracellular ATP level was
      immediately reduced by ca. 50% following the treatment with Nanogels, it was
      largely restored 24 h later. Effect of Nanogels on various respiratory components
      of cells was reversible too, and, therefore, resulted in low immediate cell
      death. Nanogel alone and formulations with AZT-TP demonstrated a much lower
      mitochondrial toxicity than AZT. As an example of potential antiviral
      applications of low-toxic Nanogel carriers, a 5'-triphosphorylated Ribavirin
      Nanogel formulation was prepared that demonstrated a 30-fold decrease in
      effective drug concentration (EC(90)) and, totally, a 10-fold increase in
      selectivity index compared to the drug alone in MDCK cells infected with
      influenza A virus.

PMID- 17509715
TI  - Improved systemic pharmacokinetics, biodistribution, and antitumor activity of
      CpG oligodeoxynucleotides complexed to endogenous antibodies in vivo.
AB  - CpG oligodeoxynucleotides (CpG-ODNs) fail to elicit antitumor immunity after
      intravenous administration presumably due to their rapid renal clearance and low
      tumor accumulation. To address this issue, we tested the hypothesis that
      endogenous IgG can be used as systemic drug carriers to improve the
      pharmacokinetics, tumor accumulation, and antitumor activity of intravenously
      administered CpG-ODNs. To this end, tritium-labeled CpG-ODNs conjugated with one
      or two dinitrophenyl (DNP) haptens (DNP- and DNP(2)-[(3)H]-CpG-ODN) were
      intravenously dosed into DNP-immunized Balb/c mice bearing subcutaneous CT26
      colorectal tumors. Serum and tissue samples for pharmacokinetic and
      biodistribution profiling were collected at predetermined timepoints and analyzed
      by liquid scintillation. In antitumor efficacy studies, DNP-immunized, CT26 tumor
      bearing mice were intravenously dosed with PBS, CpG-ODN, or DNP-CpG-ODN every
      five days. Tumor volumes and macroscopic and histological examination of resected
      solid tumors were used to quantitatively and qualitatively assess tumor growth
      inhibition. Relative to [(3)H]-CpG-ODN, dinitrophenylated [(3)H]-CpG-ODNs
      displayed substantial increases in systemic exposure (900-1650 fold) and half
      life (100-300 fold), marked decreases in systemic clearance (750-1500 fold) and
      volume of tissue distribution (13-37 fold), as well as substantial and sustained
      tumor accumulation (approximately 30% vs. <2% injected dose/g). Antitumor
      efficacy studies demonstrated that DNP-CpG-ODN inhibited tumor growth by up to
      60% relative to PBS control whereas CpG-ODN treatment had no apparent effect.
      Macroscopic and histological examination of harvested tumors at various
      timepoints revealed the presence of regions of necrotic tissue only in tumors
      from mice treated with DNP-CpG-ODN. Collectively, these results show the
      potential of endogenous IgG to mediate the systemic delivery of CpG-ODN to solid
      tumors and to enhance their antitumor activity following intravenous
      administration.

PMID- 17509716
TI  - Can we better understand the intracellular behavior of DNA nanoparticles by
      fluorescence correlation spectroscopy?
AB  - The use of non-viral gene carriers to deliver small nucleic acids like antisense
      oligonucleotides (ODNs) and small interfering RNA (siRNA) remains an attractive
      but challenging goal in antisense therapy. Indeed, different barriers need to be
      overcome in the delivery process before a therapeutic effect can be obtained. One
      promising technique which we have been evaluating to improve our understanding of
      the intracellular behavior of nucleic acids/carrier complexes is Fluorescence
      Correlation Spectroscopy (FCS). In particular, we have used FCS for studying the
      protection of the nucleic acids against enzymatic degradation, and the
      association and dissociation of the nucleic acids with their carrier, both in
      buffer and in living cells. In this report, we will review our experience and
      findings on the use of FCS for that purpose and discuss the strengths and
      weaknesses of this interesting technique.

PMID- 17509717
TI  - Biodegradable elastomeric scaffolds with basic fibroblast growth factor release.
AB  - Scaffolds that better approximate the mechanical properties of cardiovascular and
      other soft tissues might provide a more appropriate mechanical environment for
      tissue development or healing in vivo. An ability to induce local angiogenesis by
      controlled release of an angiogenic factor, such as basic fibroblast growth
      factor (bFGF), from a biodegradable scaffold with mechanical properties more
      closely approximating soft tissue could find application in a variety of
      settings. Toward this end biodegradable poly(ester urethane)urea (PEUU) scaffolds
      loaded with bFGF were fabricated by thermally induced phase separation. Scaffold
      morphology, mechanical properties, release kinetics, hydrolytic degradation and
      bioactivity of the released bFGF were assessed. The scaffolds had inter-connected
      pores with porosities of 90% or greater and pore sizes ranging from 34-173
      microm. Scaffolds had tensile strengths of 0.25-2.8 MPa and elongations at break
      of 81-443%. Incorporation of heparin into the scaffold increased the initial
      burst release of bFGF, while the initial bFGF loading content did not change
      release kinetics significantly. The released bFGF remained bioactive over 21 days
      as assessed by smooth muscle mitogenicity. Scaffolds loaded with bFGF showed
      slightly higher degradation rates than unloaded control scaffolds. Smooth muscle
      cells seeded into the scaffolds with bFGF showed higher cell densities than for
      control scaffolds after 7 days of culture. The bFGF-releasing PEUU scaffolds thus
      exhibited a combination of mechanical properties and bioactivity that might be
      attractive for use in cardiovascular and other soft tissue applications.

PMID- 17509718
TI  - Vesicles from Pluronic/poly(lactic acid) block copolymers as new carriers for
      oral insulin delivery.
AB  - The morphologies of poly(lactic acid)-b-Pluronic-b-poly(lactic acid) (PLA-F127
      PLA) aggregates in aqueous solutions were reported previously to be vesicular
      nano-particles by our group. In the present study, we seek to investigate the
      feasibility of using PLA-F127-PLA vesicles as oral delivery carrier for insulin.
      Both in vitro and in vivo release behavior of insulin loaded in PLA-F127-PLA
      vesicles were studied. A biphasic release behavior was observed for the in vitro
      release of insulin from PLAF127-29 vesicles. More importantly, it was found in
      the diabetic mice tests that the blood glucose concentration of oral insulin
      loaded PLAF127-29 vesicles decreased from 18.5 to 5.3 mmol/L within 4.5 h and the
      minimum blood glucose concentration (about 4.5 mmol/L) was achieved after about 5
      h. Furthermore, the blood glucose concentration was maintained at this level for
      at least an additional 18.5 h. These results proved that PLA-F127-PLA vesicles
      could be promising polymeric carriers for oral insulin delivery application due
      to their prolonged hypoglycemic effect.

PMID- 17509719
TI  - Anemia and clinical outcomes in hepatitis C.

PMID- 17509721
TI  - Chemoembolization of hepatocellular carcinoma with drug eluting beads.

PMID- 17509722
TI  - Ribavirin in combination therapy for HCV chronic infection in HIV patients: how
      to win the war after winning the first battle?

PMID- 17509723
TI  - Evo-devo and the evolution of social behavior.
AB  - The integration of evolutionary biology with developmental genetics into the
      hybrid field of 'evo-devo' resulted in major advances in understanding
      multicellular development and morphological evolution. Here we show how insights
      from evo-devo can be applied to study the evolution of social behavior. We
      develop this idea by reviewing studies that suggest that molecular pathways
      controlling feeding behavior and reproduction in solitary insects are part of a
      'genetic toolkit' underlying the evolution of a particularly complex form of
      social behavior, division of labor among workers in honeybee colonies. The evo
      devo approach, coupled with advances in genomics for non-model genetic organisms,
      including the recent sequencing of the honeybee genome, promises to advance our
      understanding of the evolution of social behavior.

PMID- 17509724
TI  - Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma
      and squamous cell carcinoma of the lung.
AB  - This study aimed to identify new genetic characteristics contributing to
      individual susceptibility to smoke-induced lung cancer. Despite functional
      evidence of a possible role of cytochrome P450 1A2 (CYP1A2) in lung cancer
      susceptibility, no studies have evaluated the influence of CYP1A2 genotypes on
      lung cancer risk. We investigated the interaction between CYP1A2-T2467delT
      (allele*1D) polymorphism and smoking in Tunisian lung cancer cases (n=101 male
      smokers) separately for the histological types squamous cell carcinoma (SCC)
      (n=60) and adenocarcinoma (n=41), and in controls (n=98 male smokers) using a
      case-only study design. A significant interaction between CYP1A2-T/delT or
      delT/delT genotypes and tobacco consumption (pack-years) adjusted for age was
      evident (OR (95% CI) 7.78 (1.52-42.8)) in the SCC cases who smoked relatively
      less (< or =33 pack-years, I quartile value), but not in adenocarcinoma and
      controls. Our results suggest that CYP1A2-T2467delT polymorphism has an important
      role in lung carcinogenesis, especially SCC, among smokers.

PMID- 17509725
TI  - Immunization of NSCLC patients with antigen-pulsed immature autologous dendritic
      cells.
AB  - Only a handful of NSCLC patients have been included in dendritic cell (DC)
      vaccine clinical trials. We had previously reported a series of 16 individuals
      with stages IA-IIIB NSCLC who received autologous DC vaccines matured with
      dendritic cell/T cell-derived maturation factor (DCTCMF). Here we report the
      results of a continuation study with similar inclusion criteria, immunization
      protocol, and analysis, using an immature DC vaccine. Of the 14 participants, 7
      had undergone surgical resection (stage I/II), with or without adjuvant therapy,
      and 7 with unresectable stage III had been treated with chemo-radiation alone.
      Autologous DCs were pulsed with apoptotic bodies derived from an allogeneic NSCLC
      cell line that over-expresses Her2/neu, CEA, WT1, Mage2, and survivin. DCs were
      not exposed to any maturation stimulus. Individuals received two intradermal
      vaccines (average 8.1x10(7) DC per immunization) 1 month apart. Immune responses
      were measured by IFN-gamma ELISPOT, comparing relative number of antigen-reactive
      T-cells from pre-vaccine to timepoints post-immunization. Immunologic responses
      were seen in 4/7 stage III unresectable, and 6/7 stage I/II surgically resected
      patients, including 3/3 resected patients who had also received adjuvant chemo
      radiation. There were no related adverse events. One of seven surgically resected
      patients recurred and 4/7 stage III patients progressed. Three of five patients
      with progressive disease showed no immunologic response. Data indicate that
      immature DC pulsed with apoptotic tumour cells have similar biologic activity to
      a DCTCMF-matured DC preparation delivered in a similar clinical protocol.
      Therapeutic efficacy is unknown and clinical outcomes are anecdotal.

PMID- 17509726
TI  - Factors involved in lymph node metastasis in clinical stage I non-small cell lung
      cancer--from studies of 604 surgical cases.
AB  - PURPOSE: To identify the factors involved in lymph node metastasis, 604 clinical
      stage I non-small cell lung cancer cases were studied. MATERIALS AND METHODS:
      Age, sex, Brinkmann Index (BI), histopathological type, histopathological
      differentiation degree, tumor size and CEA value were studied as factors involved
      in lymph node metastasis for 604 cases that were diagnosed to be clinical stage I
      (T1-T2N0M0; 1997 TNM categorization) non-small cell lung cancer. RESULTS: Lymph
      node metastasis was observed in 161 cases (27%). The factors involved in lymph
      node metastasis included the degree of histopathological differentiation and the
      tumor size. While the metastasis rate was less than 10% in well-differentiated
      cancers (even when the tumor size exceeded 4cm), in moderately differentiated and
      poorly differentiated cancers, the lymph node metastasis rate increased in
      proportion to tumor size. CONCLUSION: In stage I non-small cell lung cancer
      cases, cases with a low probability of lymph node metastasis are well
      differentiated cancers. In these cases, lymph node dissection may be omitted in
      surgery (reduction surgery), and such cases may thus be good subjects for
      undergoing either stereotactic body radiotherapy (SBRT) or particle therapy.

PMID- 17509727
TI  - The fungal dimension of biological invasions.
AB  - Fungi represent an essential component of biodiversity, not only because of the
      large number of species, but also for their ecological, evolutionary and socio
      economic significance. Yet, until recently, fungi received scant consideration in
      ecology, especially invasion ecology. Their under-representation is largely the
      result of a lack of scientific knowledge of fungal biodiversity and ecology. With
      the exception of pathogenic fungi, which cause emergent infectious diseases, the
      impact of fungal invasions is often difficult to quantify owing to limited
      baseline data on fungal communities. Here, we aim to raise awareness among
      mycologists and ecologists of the fungal dimension of invasions and of the need
      to intensify research in fungal ecology to address issues of future
      introductions.

PMID- 17509728
TI  - Psychological benefits of a high-protein, low-carbohydrate diet in obese women
      with polycystic ovary syndrome--a pilot study.
AB  - This study compared the psychological effects of a low-protein high-carbohydrate
      (LPHC) diet and a high-protein low-carbohydrate (HPLC) diet in women with
      polycystic ovary syndrome (PCOS). Twenty-five overweight women with PCOS were
      matched for age, weight, and whether they were trying to conceive. They were
      randomly allocated to the LPHC or HPLC diet for 16 weeks. All participants
      attended a weekly exercise, group support and educational program. The Hospital
      Anxiety and Depression Scale and the Rosenberg Self Esteem Scale were
      administered at the beginning and end of the study. The HPLC diet was associated
      with significant reduction in depression and improvement in self-esteem. There
      was no change in any psychological measures for the LPHC group. There was no
      difference in weight loss between the groups. Due to enhanced feelings of well
      being, it is possible that HPLC diets may be associated with better compliance
      and hence be more successful in the long term treatment of obesity.

PMID- 17509729
TI  - Cluster-randomized trial to improve antibiotic use for adults with acute
      respiratory infections treated in emergency departments.
AB  - STUDY OBJECTIVE: We evaluate the effectiveness of an educational program in
      hospital emergency departments (EDs) targeting reduction in antibiotic overuse
      for acute respiratory tract infections. METHODS: Sixteen hospitals participated
      in the cluster randomized trial, selecting a Veterans Administration (VA) and non
      VA hospital within each of 8 metropolitan regions. Intervention sites received
      performance feedback, clinician education, and patient educational materials,
      including an interactive computer kiosk located in the waiting room. Medical
      records were reviewed at each site during the baseline year 1 and intervention
      year 2. The primary measure of effect was the percentage of visits for upper
      respiratory tract infections and acute bronchitis that were treated with
      antibiotics. Secondary outcomes, including return visits and visit satisfaction,
      were assessed by follow-up telephone interviews of patients. Alternating logistic
      regression models were used to adjust for baseline treatment rates, case mix
      differences, and provider characteristics. RESULTS: The adjusted antibiotic
      prescription level for upper respiratory tract infection/acute bronchitis visits
      was 47% for control sites and 52% for intervention sites in year 1. Antibiotic
      prescriptions at control sites increased by 0.5% between year 1 and year 2 (95%
      confidence interval -3% to 5%) and at intervention sites decreased by 10% (95%
      confidence interval -18% to -2%). There were no significant differences between
      control and intervention sites in the proportions of upper respiratory tract
      infection/bronchitis patients with return ED visits or in overall visit
      satisfaction. CONCLUSION: Multidimensional educational interventions can reduce
      antibiotic overuse in the treatment of patients with upper respiratory tract
      infections and acute bronchitis in EDs. However, substantial antibiotic overuse
      persists despite this educational intervention.

PMID- 17509730
TI  - Survival outcomes with the introduction of intravenous epinephrine in the
      management of out-of-hospital cardiac arrest.
AB  - STUDY OBJECTIVE: The benefit of epinephrine in cardiac arrest is controversial
      and has not been conclusively shown in any human clinical study. We seek to
      assess the effect of introducing intravenous epinephrine on the survival outcomes
      of out-of-hospital cardiac arrest patients in an emergency medical services (EMS)
      system that previously did not use intravenous medications. METHODS: This
      observational, prospective, before-after clinical study constitutes phase II of
      the Cardiac Arrest and Resuscitation Epidemiology project. Included were all
      patients who are older than 8 years, with nontraumatic out-of-hospital cardiac
      arrest conveyed by the national emergency ambulance service. The comparison
      between the 2 intervention groups for survival to discharge was made with
      logistic regression and expressed in terms of the odds ratio (OR) and the
      corresponding 95% confidence interval (CI). RESULTS: From October 1, 2002, to
      October 14, 2004, 1,296 patients were enrolled into the study, with 615 in the
      pre-epinephrine and 681 in the epinephrine phase. Demographic and EMS
      characteristics were similar in both groups. Forty-four percent of patients
      received intravenous epinephrine in the epinephrine phase. There was no
      significant difference in survival to discharge (pre-epinephrine 1.0%;
      epinephrine 1.6%; OR 1.7 [95% CI 0.6 to 4.5]; adjusted for rhythm OR 2.0 [95% CI
      0.7 to 5.5]); return of circulation (pre-epinephrine 17.9%; epinephrine 15.7%; OR
      0.9 [95% CI 0.6 to 1.2]), or survival to admission (pre-epinephrine 7.5%;
      epinephrine 7.5%; OR 1.0 [95% CI 0.7 to 1.5]). There was a minimal increase in
      scene time in the epinephrine phase (10.3 minutes versus 10.7 minutes; 95% CI of
      difference 0.02 to 0.94 minutes). CONCLUSION: We were unable to establish a
      significant survival benefit with the introduction of intravenous epinephrine to
      an EMS system. More research is needed to determine the effectiveness of drugs
      such as epinephrine in resuscitation.

PMID- 17509731
TI  - Treatment of severe decompensated heart failure with high-dose intravenous
      nitroglycerin: a feasibility and outcome analysis.
AB  - STUDY OBJECTIVE: We perform a feasibility and outcome assessment of the treatment
      of severe decompensated heart failure with high-dose nitroglycerin. METHODS: This
      study was designed as a nonrandomized, open-label, single-arm study of high-dose
      nitroglycerin. Patients with hypertension (systolic blood pressure > or = 160 mm
      Hg or mean arterial pressure > or = 120 mm Hg) who were refractory to initial
      therapy were eligible for inclusion. Enrolled patients began receiving a
      titratable nitroglycerin infusion and were given a bolus of high-dose
      nitroglycerin (2 mg). Repeated administration of high-dose nitroglycerin was
      allowed every 3 minutes, up to a total of 10 doses. Predefined effectiveness and
      safety outcomes were tracked throughout hospital admission. To provide a frame of
      reference for these outcomes, data were retrospectively compiled for similar
      patients with severe decompensated heart failure who did not receive high-dose
      nitroglycerin. RESULTS: Twenty-nine patients received high-dose nitroglycerin.
      Endotracheal intubation was required in 13.8% of patients, bilevel positive
      airway pressure (BiPAP) ventilation in 6.9%, and ICU admission in 37.9%.
      Symptomatic hypotension developed in 1 patient (3.4%), and biomarker evidence of
      myocardial infarction was found in 17.2% of patients. The mean dose of high-dose
      nitroglycerin was 6.5 mg (+/-3.4). For patients who were treated without high
      dose nitroglycerin (n=45), endotracheal intubation occurred in 26.7%, BiPAP in
      20.0%, and ICU admission in 80.0%. None of these patients developed symptomatic
      hypotension, and biomarker evidence of myocardial infarction was observed in
      28.9% of patients. CONCLUSION: In this nonrandomized, open-label trial, high-dose
      nitroglycerin was associated with endotracheal intubation, BiPAP, and ICU
      admission less frequently than expected to occur without high-dose nitroglycerin,
      and adverse events were uncommon. Treatment of hypertensive, severely
      decompensated heart failure patients with high-dose nitroglycerin seems
      promising, but a randomized, blinded study is needed to more completely define
      its clinical utility. According to this trial, such a study seems feasible.

PMID- 17509732
TI  - Treatment of massive fluid overload as a result of constrictive pericarditis with
      ultrafiltration in the emergency department.
AB  - We present a case of massive fluid overload as a result of chronic lupus-related
      constrictive pericarditis, which was treated in the emergency department (ED)
      with ultrafiltration. With this novel technique, a large volume (7,350 mL) was
      extracted during 19 hours, with dramatic clinical improvement. The patient was
      hemodynamically stable throughout the intervention, and the procedure was
      tolerated without complication. This report highlights the challenges associated
      with the treatment of such individuals and the potential benefits of
      ultrafiltration in the ED setting.

PMID- 17509733
TI  - Biological studies of new organotin(IV) complexes of thioamide ligands.
AB  - New organotin(IV) complexes with heterocyclic thioamides 2-mercapto-benzothiazole
      (Hmbzt), 5-chloro-2-mercapto-benzothiazole (Hcmbzt) and 2-mercapto-benzoxazole
      (Hmbzo) of formulae [(C(6)H(5))(3)Sn(mbzt)] (1), [(C(6)H(5))(3)Sn(cmbzt)] (3) and
      [(C(6)H(5))(2)Sn(cmbzt)(2)] (4), together with the already known
      [(C(6)H(5))(3)Sn(mbzo)] (2), [(n-C(4)H(9))(2)Sn(cmbzt)(2)] (5) and
      [(CH(3))(2)Sn(cmbzt)(2)] (6) were used to study their influence on the
      peroxidation of oleic acid. The influence of complexes (3)-(6) upon peroxidation
      of oleic acid showed that the formation of reactive radicals caused the
      initiation of the chain radical oxidation of the substrate. The influence of
      complexes (1)-(6) upon the catalytic peroxidation of linoleic acid by the enzyme
      lipoxygenase (LOX) was also studied and compared to those of cisplatin. Compounds
      (1)-(6) were finally tested for in vitro cytotoxicity against leiomyosarcoma
      cells.

PMID- 17509734
TI  - The preclinical testing of a formaldehyde inactivated Ross River virus vaccine
      designed for use in humans.
AB  - Ross River virus was grown in industrial facilities in vaccine-certified Vero
      cells in the absence of serum, inactivated using standard formalin-inactivation
      protocols, treated with Benzonase to digest host cell DNA and purified on a
      sucrose gradient. Mice given two subcutaneous injections of 0.625 microg of this
      vaccine or two doses of 0.156 microg vaccine with aluminium hydroxide adjuvant
      failed to develop a detectable viraemia after intravenous challenge with
      10(6)TCID50 of the prototype strain of Ross River virus (T48). Guinea pigs
      immunised with one or two10 microg doses of vaccine with adjuvant also failed to
      develop a detectable viraemia following a similar challenge. The levels of
      neutralising antibody (neutralisation index 1.9-3.1) in the mice protected
      against challenge with 10(6)TCID50 Ross River virus were similar to those in 16
      former epidemic polyarthritis patients (1.1-3.5) who had not experienced a second
      clinical infection with Ross River virus in the 20 years following their initial
      infection.

PMID- 17509735
TI  - Improvement of a commercial foot-and-mouth disease vaccine by supplement of Quil
      A.
AB  - In model animal experiment A, ICR mice were immunized with ovalbumin (OVA)
      adjuvanted with Quil A or mineral oil or their combination (Quil A+oil). In model
      animal experiment B, ICR mice were immunized with foot-and-mouth disease virus
      (FMDV) antigens or with a commercially available oil adjuvanted foot-and-mouth
      disease (FMD) vaccine (type O) alone or mixed with Quil A. After that, serum
      samples were collected to analyze specific IgG and IgG subclasses IgG1, IgG2a,
      IgG2b, and IgG3. In experiment C, pigs were immunized with FMD (type O) vaccine
      alone or together with Quil A. Serum samples were collected before and 4 weeks
      after immunization to analyze indirect haemagglutination (IHA) titers. Results
      from experiment A indicated a synergistic effect of Quil A and oil on IgG and the
      subclass responses. Experiment B revealed that supplement of Quil A in FMD
      vaccine significantly increased IgG and the subclass responses in mice.
      Experiment C demonstrated that supplement of Quil A in the FMD vaccine
      significantly enhanced humeral immune responses (as determined by IHA test) in
      pigs. It is concluded that supplement of Quil A in FMD vaccine can significantly
      enhanced immune responses and could be an alternative way to improve FMD
      vaccination in pigs.

PMID- 17509736
TI  - Penetrating pneumatic nail-gun injury to skull base.

PMID- 17509737
TI  - Juggling type 1 diabetes and pregnancy in rural Australia.
AB  - OBJECTIVE: to explore the experiences of women with type 1 diabetes, living in
      rural Australia, while preparing for pregnancy and childbirth. Additionally, we
      aimed to describe the women's engagement with, and expectations of, health-care
      providers during this period, and subsequently highlight potential service and
      informational gaps. DESIGN: qualitative research using a collective case-study
      design; seven women with type 1 diabetes who had given birth within the previous
      12 months participated in in-depth interviews about their experiences of
      pregnancy and birth. Data were analysed thematically. SETTING: The experience of
      type 1 diabetes, preconception preparation and pregnancy among rural Australian
      women was explored, including interactions with health professionals.
      PARTICIPANTS: seven women aged between 26 and 35 years agreed to be interviewed.
      The woman had one or two children and had given birth within the past 12 months.
      FINDINGS: rigid narrow control of blood glucose levels before conception and
      during pregnancy created unfamiliar body responses for women, with hypoglycaemic
      symptoms disappearing or changing. For example, some women mentioned developing
      tunnel vision or numbness and tingling around their lips and tongue as different
      symptoms of hypoglycaemia. Women needed information and support to differentiate
      between what might be normal or abnormal bodily processes associated with
      pregnancy, diabetes, or both. The women's preparation for conception and
      pregnancy was reliant on the level of available expertise and advice.
      Participants' experiences were coloured by their limited access and interactions
      with expert health professionals. CONCLUSION: women with type 1 diabetes
      experienced significant hardship during their pregnancy, including a higher
      incidence of hypoglycaemic episodes, a loss of hypoglycaemic symptom recognition
      and weight gain. These difficulties were compounded by a scarcity of available
      information to support the management of their pregnancy and a lack of
      availability of experienced health professionals. IMPLICATIONS FOR PRACTICE:
      national and international consensus guidelines emphasise the importance of
      preconception and pregnancy care for women with type 1 diabetes. Close clinical
      supervision and the development of closer co-operation and partnership between
      the women and health-care providers before conception and during pregnancy may
      improve outcomes for these women and their babies. Building confidence in
      professional care requires increased access to specialist services, increased
      levels of demonstrated knowledge and expertise and better general community
      access to information about preparation for pregnancy and birth among women who
      have type 1 diabetes.

PMID- 17509738
TI  - Short rest between cyclic flexion periods is a risk factor for a lumbar disorder.
AB  - BACKGROUND: The epidemiology identifies cyclic lumbar loading as a risk factor
      for cumulative trauma disorder. Experimental biomechanical and physiological
      confirmation is lacking. The objective of this study was to asses the impact of
      different rest durations applied between periods of cyclic loading on the
      development of an acute lumbar disorder which, if continued to be subjected to
      loading, may develop into a cumulative disorder. METHODS: Three groups of in vivo
      feline preparations were subjected to six sequential 10 min loading periods of
      cyclic lumbar flexion at 40 N with a frequency of 0.25 Hz applied to the L-4/5
      level. The rest durations varied from 5 min in the first group, to 10 min in the
      second and to 20 min in the third. Reflexive EMG from the multifidi and lumbar
      displacement were used to identify significant (P<0.001) effects of time and rest
      duration for post-load EMG and displacement. Single-cycle test were performed
      hourly for 7 h post-loading to assess recovery. A model developed earlier was
      applied to represent the experimental data. FINDINGS: The groups allowed 5 and 10
      min rest exhibited an acute neuromuscular disorder expressed by a significant
      (P<0.001) delayed hyperexcitability 2-3 h into the 7 h recovery period with the
      intensity of the hyperexcitability significantly higher (P<0.001) for the group
      allowed only 5 min rest. The group allowed 20 min rest had a slow, uneventful
      recovery, free of delayed hyperexcitability. INTERPRETATIONS: Occupational and
      sports activities requiring repetitive (cyclic) loading of the lumbar spine may
      be a risk factor for the development of a cumulative lumbar disorder and may
      require sufficient rest, as much as twice as long as the loading period, for
      prevention. Comparison to similar data for static lumbar loading shows that
      cyclic loading is more deleterious than static loading, requiring more rest to
      offset the negative effect of the repeated acts of stretch.

PMID- 17509739
TI  - Internalizing symptoms and disorders in families of adolescents: a review of
      family systems literature.
AB  - Internalizing symptoms and disorders are relatively common during adolescence and
      impact considerably on social and emotional functioning. Using a family systems
      framework, this paper reviews the current literature examining the impact of
      internalizing symptoms and disorders on the functioning of the family system, the
      spouse subsystem and the parent-child subsystem. Moreover, literature examining
      the relationship between parents' and adolescents' internalizing symptoms and
      disorders is reviewed. The reviewed research demonstrates that there exists an
      association between internalizing symptoms and disorders and poorer functioning
      at various levels of the family system. Longitudinal studies have generally
      reported that parent internalizing symptoms and disorders predict poorer
      functioning in the family system as well as internalizing symptoms and disorders
      in adolescents. However, few longitudinal studies have examined whether
      adolescent internalizing symptoms and disorders predict poorer family functioning
      and internalizing symptoms and disorders in parents. Those that have examined
      such effects report mixed results. On the basis of our review, we make
      recommendations about future research directions. In particular, it is argued
      that more research on the reciprocal effects of internalizing symptoms and
      disorders within families is needed to better understand the antecedents and
      consequences of these conditions for families of adolescents.

PMID- 17509740
TI  - Limits and prospects of the "incremental approach" and the European legislation
      on the management of risks related to nanomaterials.
AB  - Scientific uncertainty involved in evaluating potentially harmful properties of
      engineered nanoparticles complicates and hampers the implementation of
      proportionate regulative measures by legislators. The European Commission has
      adopted a so-called "incremental approach", which focuses on adapting existing
      laws to regulate nanotechnologies, and therefore this paper aims to test the
      effectiveness of the "incremental approach". Three commercially available
      products containing fullerenes (C(60) and carbon nanotubes) were analysed in a
      life cycle perspective in order to (1) map current applicable regulations, (2)
      analyse their applicability to nanomaterials, (3) identify their gaps, and (4)
      suggest proper solutions. After mapping the life cycle of the three products, we
      analysed applicable regulations in the order in which they became relevant in
      their life cycle, i.e.: The Safety at Workplace Directives. Directive 61/1996 on
      the Integrated Pollution Prevention and Control. The European Union's Directive
      on the Registration, Evaluation, Authorization and Restriction of Chemicals, and
      The Waste Management Directives. It was found that the applicability of
      environmental laws is limited due to difficulties in generating sufficient data
      on the nanomaterials residing in the products according to their life cycles.
      Further, metrology tools are unavailable; thresholds are not tailored to the
      nanoscale; and toxicological data and occupational exposure limits cannot be
      established with existing methodologies. We conclude that the "incremental
      approach" can only be applicable with the implementation of due amendments.

PMID- 17509741
TI  - Social networks, normative influence and health delivery in rural Bangladesh.
AB  - This paper examines the association of social networks with the experience of
      neonatal death and the type of assistance that a woman obtains at childbirth in
      rural Bangladesh. Data were collected by interviewing 694 women from seven
      villages using a structured questionnaire. From the use of both social network
      analysis and statistical methods, we find that the experience of neonatal death
      and the type of assistance that a woman gets at childbirth are associated with
      the characteristics of their social networks along with a set of socioeconomic
      factors that are usually considered to be important. The higher the degree of
      centrality of a woman in her social network, the less likely it is that she will
      experience neonatal death, and the experience of neonatal death is significantly
      associated with the type of assistance she obtained at giving birth. Using a
      multivariate multinomial logistic regression model to explore the likelihood of
      using different types of birth assistance, we find that the higher the degree
      centrality of a woman, the less likely she will be attended by professional
      assistance. Further investigations reveal that the dominant norm in villages is
      to use traditional birth attendants and the perception about professional birth
      assistance is that it is 'not needed'. Moreover, the respondents' network members
      were also interviewed, and from the sociograms we find that there was an inward
      connectivity between the same types of assistance users. These findings have
      implications for norm change interventions among the village women using a
      network approach and in particular using opinion leaders.

PMID- 17509742
TI  - Temporal changes in the spatial pattern of disease rates incorporating known risk
      factors.
AB  - Examining the geographical pattern of temporal changes in infant mortality rates
      illustrates the methodological problems of documenting and understanding temporal
      changes in any spatial pattern of disease. Early research on geographical
      differences in infant mortality rates showed strong ecological correlations with
      socio-economic factors such as poverty rates. More recent research established
      relationships between individual-level socio-economic values and probabilities of
      death. With geographic information available at the level of individuals, it is
      possible to estimate the probabilities of death on a person-by-person basis from
      knowledge of the relationships between individual factors and socio-economic
      measures. These estimated probabilities provide an expected geographic pattern of
      deaths. The difference between the observed spatial pattern and the expected
      pattern is the remaining spatial variation adjusted for this knowledge. For the
      study area, individual factors and some socio-economic measures were available
      for each year of the study period. Using data from the Iowa Birth Defects
      Registry and the Iowa Department of Public Health (USA), I tested the stability
      and continuity of these cross-sectional relationships and investigated whether
      any temporal lags in these variables relate to the unexplained spatial variations
      in infant mortality rates that remain. I accounted for the 'Change of Support
      Problem' [Gotway C. A. & Young L. J. (2002). Combining incompatible spatial data.
      Journal of the American Statistical Association, 97458, 632-648] inherent in
      frame-based geographical analysis. The analysis involved a generalized linear
      model (GLM) to estimate individual risks and a Monte Carlo simulation model to
      generate the non-linear probability density functions for disease rates whose
      densities are theoretically intractable. Results show the temporal changes in the
      observed spatial pattern and the expected spatial pattern differ by geographic
      location. In conclusion such differences are the result of a combination of
      unexplained place-based risk and unmeasured individual risks.

PMID- 17509743
TI  - The social consequences of living with and dealing with incontinence--a carers
      perspective.
AB  - Incontinence is a discrediting and stigmatising condition for those who
      experience it, as it signifies a person who is lacking in self-control. For their
      carers, the very nature of undertaking 'dirty work' signifies a low status and
      low paid job. Those health care professionals higher in status and financial
      reward put distance between themselves and bodywork, especially bodywork that
      deals with bodily decay. However, little is known or has been highlighted about
      the social consequences that living with and dealing with incontinence can have
      on informal carers. In this paper we examine the notion of dirty work and
      'unbounded' bodies in the role of informal carers. Through qualitative interviews
      with carers of stroke survivors the negative social consequences of dealing with
      incontinence for both the survivor and the carer are explored. We also examine
      the strategies employed by carers and stroke survivors in order to manage the
      symptom in an attempt to prove the adult status of the survivor and to protect
      both the identity of the survivor and the carer. The embarrassment of leakage and
      the moral danger of odour can lead some carers and survivors to make decisions
      that can isolate both within the confines of their home. In this sense the very
      meaning of home is transformed into an isolated and marginalised space.

PMID- 17509744
TI  - Effect of 40% chlorhexidine varnish on mutans streptococci counts in pits and
      fissures of permanent first molars.
AB  - OBJECTIVES: This study aimed to test the following hypotheses: (1) a carry-over
      effect of EC40 does not occur in a split-mouth model, (2) two consecutive
      applications of EC40 varnish with an interval of 3 months per year has a better
      inhibiting effect on mutans streptococci in pit and fissure plaque of permanent
      first molars of 6-7-year olds than a repeated application at each 6 months and
      (3) EC40 exerts an inhibiting effect on mutans streptococci for at least a 6
      month duration. METHODS: Using a split-mouth design, test molars received EC40 on
      fissures and pits and control molars remained without treatment. One group of
      test molars received EC40 at baseline, 6, 12 and 18 months and another group at
      baseline, 3, 12 and 15 months. Plaque samples were taken from pits and fissures
      of test and control molars at baseline, 6, 9, 12 and 24 months. A mixed ANOVA
      model was used to analyze the data. RESULTS: The first hypothesis was accepted,
      the second rejected and the third accepted. CONCLUSIONS: Twice a year EC40
      application on pits and fissures of permanent first molars of 6-7-year-old
      children can significantly reduce mutans streptococci numbers for a 6-month
      period, but the reductions were small.

PMID- 17509745
TI  - Inhibition of PAI-1 expression in breast cancer carcinoma cells by siRNA at
      nanomolar range.
AB  - Plasminogen activator inhibitor type I (PAI-1) plays a central role in metastatic
      behavior by increasing cells' migratory capacities as shown in several tumoral
      cell lines. Moreover, in vivo high expression of this factor helps tumoral
      growth, both by its role in extracellular matrix remodeling and by favoring
      angiogenesis. High levels of PAI-1 are correlated with bad prognosis in several
      cancers, particularly in breast cancer. The effect of PAI-1 upon angiogenesis is
      also involved in atherosclerosis, in which high levels of PAI-1 expression are
      observed. Breast carcinoma MDA MB 231 cells are known for both having important
      metastatic capacities and expressing high levels of PAI-1. We have demonstrated
      in these cells that the transfection of PAI-1 specific small interfering RNAs
      (siRNA) specifically inhibited the expression of this factor by 91%. We evaluated
      siRNA activity by determining PAI-1 mRNA level, as well as intracellular and
      extracellular PAI-1 protein by using RT Q-PCR, Western blot and ELISA analyses,
      respectively. Data confirmed inhibition at mRNA levels (primary aim of
      interference), intracellular protein, and secreted PAI-1, the latter being
      operative successfully in the cell microenvironment. The lipidic vector Delivery
      Liposomes System (DLS) used was adapted to siRNA delivery as observed by particle
      size distribution analysis, confocal microscopy and transfection into MDA MB 231,
      in the presence of serum. SiRNA activity was clearly detected at concentrations
      as low as 10 nM. Moreover, the low cytotoxicity of this vector makes it a good
      candidate for future in vivo siRNA delivery.

PMID- 17509746
TI  - Impact of the earthquake and tsunami of December 26, 2004, on the groundwater
      regime at Neill Island (south Andaman).
AB  - The aquifer and groundwater regime has been affected by the earthquake and
      tsunami of December 26, 2004, particularly on the islands and coastal regions of
      India. The groundwater regime on many islands of Andaman and Nicobar islands,
      which is the only source of fresh water on the islands, has been found to be
      deteriorated. Detailed hydrogeological studies have been carried out at one of
      the tiny islands of Andaman, namely Neill Island, and results have been compared
      with prior observations. It has been found that the shell limestone aquifer at a
      few places has developed cracks due to the earthquake and these openings have
      allowed quick movement of seawater into the aquifer resulting into deterioration
      of groundwater quality. In the places where the aquifer is at sea level, the
      tsunami waves have caused seawater ingress. Most parts of the island which have
      hard mudstone as a base and where the aquifer lies much above sea level, did not
      show any change in groundwater regime.

PMID- 17509747
TI  - Glucose enhances protein tyrosine phosphatase 1B gene transcription in
      hepatocytes.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin
      receptor signal transduction pathway. We investigated the effects of glucose on
      PTP1B transcription in the human hepatocyte cell line Huh7. Using a reporter gene
      assay, we found that D-glucose dose-dependently enhanced the PTP1B promoter
      activity. Real-time PCR demonstrated that D-glucose also increased PTP1B mRNA
      expression. Protein kinase C (PKC) inhibitors partially but significantly
      inhibited the transactivation by D-glucose. Mithramycin, a Sp1 inhibitor,
      completely abrogated this transactivation. The deletion of three possible Sp1
      sites in the promoter region of PTP1B significantly reduced the basal promoter
      activity and transactivation by D-glucose. Sp1 activation by PKC is one of the
      key mechanisms in the regulation of several gene expressions. Our data suggested
      that glucose enhanced PTP1B transcription through Sp1 activation by PKC.
      Increased hepatic PTP1B expression may partly explain glucose toxicity in
      diabetes.

PMID- 17509748
TI  - Relaxin signalling in THP-1 cells uses a novel phosphotyrosine-dependent pathway.
AB  - The heterodimeric peptide hormone relaxin acts through the novel G-protein
      coupled receptor LGR7 to elicit the production of cAMP in the human monocyte cell
      line THP-1. The very small number of receptors on the cell surface, and the lack
      of response in cell membranes imply the involvement of a cytoplasmic signal
      amplification process. Here we show that this process comprises a novel and
      specific tyrosine kinase activity close to the receptor, and involves neither
      protein kinase A, mitogen-activated protein kinase, nor phosphoinositide-3 kinase
      activities as major upstream components. Furthermore, this novel involvement of a
      tyrosine kinase activity is cell-type dependent, being largely absent from LGR7
      transfected HEK293T cells, and receptor-dependent; vasoactive intestinal peptide
      or isoproterenol signalling in the same cells does not require this tyrosine
      kinase activity.

PMID- 17509749
TI  - Carotid "trifurcation" aneurysm: surgical anatomy and management.
AB  - The authors describe a rare case of internal carotid artery (ICA) trifurcation
      aneurysm and its surgical management. Carotid trifurcation is a unique anatomical
      variant where three arterial branches arise from the carotid termination than the
      usual two. Aneurysm arising from the trifurcation, due to its rarity, is
      difficult to treat. The anatomy, embryological basis and significance of such an
      anomaly during surgical management are discussed.

PMID- 17509750
TI  - Seizures and epilepsy in patients with a spontaneous intracerebral haematoma.
AB  - BACKGROUND: Seizures occur more frequently in patients with an intracerebral
      haematoma (ICH) than in those with a cerebral infarct. However, the risk factors
      for seizures in association with an ICH are less well known. PURPOSE: The
      characteristics of medically treated patients with spontaneous ICHs, who
      developed seizures, were retrospectively compared to those who did not. PATIENTS:
      Fourteen patients were admitted to the Stroke Unit during 2004-2006 for seizures
      related to an ICH. Their characteristics were compared to those of 51 patients
      admitted during 2002-2004 for an ICH without subsequent seizures. RESULTS: Early
      onset seizures, occurring within 48 h of stroke onset, were observed in six
      patients with ICH related epileptic spells (42.9%). Late-onset ones occurred in
      eight patients, on average 8 months after the ICH. A focal onset of the seizures
      was documented in 75.7% of cases. Status epilepticus was observed in 21.4% of the
      patients. The seizures recurred in only 28.6% of the patients. Lobar haematomas
      were present in 78.6% of the seizure group, compared to 21.4% in the control
      group (P=0.008). In the former group a frontal lobe involvement was present in
      57.1% compared to 9.8% in the latter group (P<0.001). On the post-ictal EEG,
      intermittent rhythmic delta activities were observed in 28.6% and periodic
      lateralized epileptic discharges in 21.4% of the seizure patients. CONCLUSIONS:
      Seizures are more prone to occur in patients with frontal lobar haematomas. EEG
      can be helpful for the diagnosis of seizures in approximately 50% of the cases.

PMID- 17509751
TI  - The effect of levodopa on respiration and word intelligibility in people with
      advanced Parkinson's disease.
AB  - OBJECTIVES: Hypokinetic dysarthria is commonly encountered in Parkinson's disease
      (PD). Although the etiology of this dysarthria is multifactorial, disorders of
      respiration may strongly contribute to it. The aim of this study was to evaluate
      the effects of levodopa on measures of respiration and intelligibility. PATIENTS
      AND METHODS: Vital capacity (VC), sustained vowel phonation (SVP) and phonation
      quotient (PQ) were determined with and without medication in 25 patients
      suffering from idiopathic PD. Intelligibility was evaluated by three independent
      speech pathologists using the word subtest protocol of the Yorkston and Beukelman
      "Assessment of intelligibility of dysarthric speech" (AIDS). RESULTS: VC was
      abnormal in 18/25 patients in the off-condition and 15/25 in the on-condition.
      SVP was normal in 22/25 patients in the off-state and in all patients in the on
      state. PQ was normal in all patients in the off- and on-condition. All three
      respiratory parameters, as well as intelligibility, improved significantly
      following administration of levodopa. There were significant differences between
      men and women for VC and PQ, with men having the highest values for both
      parameters in both conditions. In none of the two conditions a correlation
      between respiratory parameters and intelligibility could be demonstrated.
      CONCLUSION: This study suggests that thoracic mobility is decreased in PD, and
      that pharmacological treatment results in improvement, but not in normalization.
      Moreover, it remains unclear to what extent dyskinesias negatively influence
      respiratory control. Our results also demonstrate improvement of intelligibility
      after pharmacological treatment of PD. However, this improvement is not solely
      the consequence of respiratory changes. Further research on the effects of
      different characteristics on intelligibility is necessary.

PMID- 17509752
TI  - Addenbrooke's Cognitive Examination (ACE) for the diagnosis and differential
      diagnosis of dementia.
AB  - OBJECTIVES: The Addenbrooke's Cognitive Examination (ACE) is reported to be a
      highly sensitive and specific "bedside" test for the diagnosis of dementia, but
      large pragmatic studies of its use in day-to-day clinical practice are lacking.
      This study measured diagnostic accuracy of ACE in a large cohort of consecutive
      patients referred to a dedicated Cognitive Function Clinic. PATIENTS AND METHODS:
      Consecutive new referrals over a 3.5-year period were administered the ACE
      (n=285). ACE scores and subscores (VLOM ratio) were compared to clinical
      diagnoses of dementia and dementia subtype, established on the basis of widely
      accepted diagnostic criteria and at least 12-month follow-up. RESULTS: ACE had
      good sensitivity, specificity, and positive predictive value for the diagnosis of
      dementia, with excellent diagnostic accuracy as measured by area under the
      receiver operating characteristic curve. However, a lower cutoff than that used
      in the index paper was required for optimum test sensitivity and specificity. ACE
      VLOM ratio subscore for the differential diagnosis of Alzheimer's disease and
      frontotemporal dementia proved less accurate. CONCLUSION: This study suggests
      that ACE is useful for the diagnosis of dementia in routine clinical practice but
      that other instruments may be required for the differential diagnosis of the
      dementia syndrome.

PMID- 17509753
TI  - Middelheim Fabry Study (MiFaS): a retrospective Belgian study on the prevalence
      of Fabry disease in young patients with cryptogenic stroke.
AB  - OBJECTIVE: To assess the prevalence of Fabry disease in young patients with
      cryptogenic stroke. PATIENTS AND METHODS: We retrospectively assessed the
      prevalence of Fabry disease in patients aged 16-60 years that were admitted to
      ZNA Middelheim Hospital from January 1, 2000 to December 31, 2004 for cryptogenic
      stroke. We screened for Fabry disease by measurement of alpha-galactosidase A and
      beta-glucuronidase activity on blood spot. In all patients with abnormal
      enzymatic activity and in all female patients with low normal values, genetic
      sequencing of the alpha-GAL-gene was performed. RESULTS: In a population of 103
      young patients with cryptogenic stroke that met the in- and exclusion criteria,
      we were unable to identify any patient with Fabry disease. CONCLUSION: Based on
      the results of alpha-galactosidase A and beta-glucuronidase activity, genetic
      sequencing and the low prevalence of clinical signs and symptoms of Fabry disease
      in this population, we believe that the true prevalence of Fabry disease in
      patients with cryptogenic stroke may be less than currently accepted in
      literature.

PMID- 17509754
TI  - Photocatalytic and electrochemical combined treatment of textile wash water.
AB  - Various chemical and physical processes for treatment of textile effluent are not
      destructive but they only transfer the contaminants from one form to another. The
      presence of high concentration of organic dye and total dissolved solids (TDS) in
      the effluent that are not removed by biological treatment must be eliminated by
      an alternative method to the conventional ones is the advanced oxidation process
      (AOP). A procion blue dye effluent was treated by photo and electrochemical
      oxidation process as well as by combining photocatalytic degradation using TiO2
      suspensions. Chemical oxygen demand (COD) and colour removal can be used to
      follow the degradation of the organic pollutant. The effects of pH, current
      density, flow rate of effluent that passes into the reactor and supporting
      electrolyte were studied. Comparative studies were carried out on photocatalytic
      and electrochemical process to degrade the procion blue. The maximum COD
      reduction and colour removal were 96 and 100%, respectively. Photodegradation
      efficiency of dye was high when photolysis was carried out in the presence of 40
      mg/l of TiO2.

PMID- 17509755
TI  - Influence of the demineralisation on the chemical activation of Kraft lignin with
      orthophosphoric acid.
AB  - The preparation of activated carbons (ACs) from the thermal decomposition of
      mixtures of orthophosphoric acid (PA) and either as-received softwood Kraft
      lignin, KL, or demineralised one, KL(d), has been investigated. Activation with
      PA has been studied for a PA/lignin ratio of 1 (dry ash-free basis) and 1h
      carbonisation time at final temperatures of 400, 500 and 600 degrees C. The
      yield, surface area, porosity, surface chemistry and methylene blue adsorption
      capacity have been determined. All ACs were found to be essentially microporous,
      with surface areas higher than 800 m(2)/g and a maximum value of nearly 1200
      m(2)/g for the carbon prepared at 600 degrees C from KL. In order to study the
      influence of temperature on the properties of the ACs prepared from KL and KL(d),
      the latter precursors were analysed by Fourier transform infrared spectroscopy
      (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (XRD). We have
      concluded that the very different characteristics of the ACs obtained from KL and
      KL(d) are due to the presence or not of mineral matter during carbonisation, but
      mainly to the demineralisation process itself, which produces polymerisation of
      the raw lignin. Methylene blue adsorption was found to be higher for ACs prepared
      from KL, mainly because of their higher ash and sulphur contents.

PMID- 17509756
TI  - WITHDRAWN: Selective spectrophotometric determination of cobalt(II) in various
      environmental samples with 2-(chromen-2'-onyl)-5(4''-chlorophenyl)1,3,4
      oxadiazole.
AB  - The present work describes a selective, rapid and economical spectrophotometric
      method for the determination of cobalt(II) in various environmental samples. The
      method is based on the formation of pink colored complex of a stoichiometric
      ratio 1:2 between cobalt(II) and 2-(chromen-2'-onyl)-5-(4''-chlorophenyl)1,3,4
      oxadiazole at pH 6.0+/-0.2. The absorbance of the complex was measured
      spectrophotometrically at 542nm. Under the optical conditions, Beer's law was
      obeyed over the range of 0.5-14mugml(-1). The molar absorptivity and Sandell's
      sensitivity were 1.348x10(4)lmol(-1)cm(-1) and 0.004115mugcm(-2), respectively.
      The detailed study of various interferences made the method more selective. The
      method was successfully applied to the determination of cobalt(II) in various
      environmental samples. The performance of proposed method was evaluated in terms
      of Student's t-test and variance ratio f-test which indicates the significance of
      proposed method over reported method. Recoveries obtained revealed that the
      proposed procedure shows good accuracy at 98% confidence level.

PMID- 17509757
TI  - Comments on recently reported performances of solid wastes as fuels in France.

PMID- 17509758
TI  - Equilibrium, kinetic and thermodynamic studies on the adsorption of m-cresol onto
      micro- and mesoporous carbon.
AB  - Investigations were conducted in batch mode to study the adsorption behaviour of
      m-cresol on a porous carbon prepared from rice husk (RHAC) by varying the
      parameters such as agitation time, m-cresol concentration (50-300 mg/l), pH (2.5
      10) and temperature (293-323 K). Studies showed that the adsorption decreased
      with increase in pH and temperature. The isotherm data were fitted to Langmuir,
      Freundlich, and Dubinin-Radushkevic (D-R) models. The kinetic models such as
      pseudo-first-order, pseudo-second-order and intraparticle diffusion models were
      selected to understand the reaction pathways and mechanism of adsorption process.
      The thermodynamic equilibrium coefficients obtained at different temperatures
      were used to evaluate the thermodynamic constants DeltaG degrees, DeltaH degrees
      and DeltaS degrees. The sorption process was found to be exothermic in nature
      (DeltaH degrees : -23.46 to -25.40 kJ/mol) with a decrease in entropy (DeltaS
      degrees: -19.44 to -35.87 J/(mol K)). The negative value of Gibbs free energy,
      DeltaG degrees indicates that the adsorption occurs via a spontaneous process.
      The decrease in the value of -DeltaG degrees from 17.70 to 13.54 kJ/mol with
      increase in pH and temperature indicates that the adsorption of m-cresol onto
      activated carbon is less favourable at higher temperature and pH range. The
      influence of mesopore and a possible mechanism of adsorption is also suggested.

PMID- 17509759
TI  - Optimization of an open-focused microwave oven digestion procedure for
      determination of metals in diesel oil by inductively coupled plasma optical
      emission spectrometry.
AB  - This work reports the optimization of a focused microwave assisted procedure for
      the wet acid dissolution of diesel oil in order to allow the determination of
      metals in the samples by inductively coupled plasma optical emission spectrometry
      (ICP-OES). The dissolution process was monitored by measuring residual carbon
      content (RCC), also by ICP-OES, in the final solutions obtained after application
      of digestion program. All experimental work was performed using a commercial
      sample of diesel oil containing 85.74+/-0.13% of carbon. The initial dissolution
      program comprised three steps: (i) carbonization with H(2)SO(4); (ii) oxidation
      with HNO(3) and (iii) final oxidation with H(2)O(2). During work it was verified
      that the first step played an important role on the dissolution process of this
      kind of sample. It is therefore, necessary to give a detailed optimization of
      such step. Employing the optimized conditions it was possible to digest 2.5 g of
      diesel oil with a 40 min-heating program. At these conditions, residual carbon
      content was always lower than 5%. Optimized methodology was applied in the
      determination of metals in three diesel oil samples by ICP-OES. Recovery tests
      were also performed by adding 10 microg of metals, as organic standards, to the
      samples before digestion. Recovery percentages always higher than 90% were
      obtained for the metals of interest (Al, Cu, Fe and Ni), except for Zn, which
      presented recoveries between 70 and 78%.

PMID- 17509760
TI  - Validation of a pictorial rating scale for grip strength evaluation in 3- to 6
      year-old children.
AB  - The present study aimed to validate a pictorial rating scale to evaluate the
      child's ability to produce grip forces. Thirty-seven children aged 3 to 6 years
      participated as subjects in this investigation. We used a tailor-made pictorial
      scale and a hand grip strength meter, as well as a Piaget's clinical interview
      aimed to gather information on the child's understanding of the rating scale. The
      sensitivity of the rating scale was measured by testing a 4-intensity-level hand
      grip effort with 3- to 6-year-old children. In addition, the reproducibility of
      this pictorial rating scale was investigated by a test and randomised re-test
      procedure. Statistical analysis revealed that no significant main effect (P>0.05)
      for test was observed in any child. In addition, no significant main effect
      (P>0.05) for intensity was found in 3-year-old children. However, in the 4-year
      old children and over, a significant main effect (P<0.05) was found for
      intensity. The results also showed that 5- and 6-year-old children were able to
      produce four differentiated intensities of grip forces. These findings suggest
      that the pictorial rating scale for grip strength evaluation showed acceptable
      reproducibility and was sensitive to the age of the children tested. To conclude,
      this pictorial rating scale appears to be a valid tool to investigate accurately
      the child's ability to produce grip forces in young children from 5-year-old and
      over.

PMID- 17509761
TI  - Body perception disturbance: a contribution to pain in complex regional pain
      syndrome (CRPS).
AB  - In spite of pain in the CRPS limb, clinical observations show patients pay little
      attention to, and fail to care for, their affected limb as if it were not part of
      their body. Literature describes this phenomenon in terms of neurological neglect
      like symptoms. This qualitative study sought to explore the nature of the
      phenomenon with a view to providing insights into central mechanisms and the
      relationship with pain. Twenty-seven participants who met the IASP CRPS
      classification were interviewed using qualitative methods to explore feelings and
      perceptions about their affected body parts. These semi-structured interviews
      were analysed utilising principles of grounded theory. Participants revealed
      bizarre perceptions about a part of their body and expressed a desperate desire
      to amputate this part despite the prospect of further pain and functional loss. A
      mismatch was experienced between the sensation of the limb and how it looked.
      Anatomical parts of the CRPS limb were erased in mental representations of the
      affected area. Pain generated a raised consciousness of the limb yet there was a
      lack of awareness as to its position. These feelings were about the CRPS limb
      only as the remaining unaffected body was felt to be normal. Findings suggest
      that there is a complex interaction between pain, disturbances in body perception
      and central remapping. Clinically, findings support the use of treatments that
      target cortical areas, which may reduce body perception disturbance and pain. We
      propose that body perception disturbance is a more appropriate term than 'neglect
      like' symptoms to describe this phenomenon.

PMID- 17509762
TI  - A role for peripheral afferents in the pathophysiology and treatment of at-level
      neuropathic pain in spinal cord injury? A case report.
AB  - At-level neuropathic pain is a frequent symptom following spinal cord injury, but
      the underlying pathophysiology is not completely understood. We report a patient
      suffering from treatment-resistant at-level pain characterized by ongoing pain
      and mechanical allodynia for three years after an incomplete spinal lesion.
      Quantitative sensory testing revealed severe thermosensory deficits in the
      neuropathic pain area. However, topical application of capsaicin in the
      neuropathic pain area induced a burning pain sensation, a marked decrease in heat
      pain threshold and an increase in mechanical allodynia. Treatment with topical
      lidocaine patches (5%) led to considerable pain relief. These results indicate a
      functional connection between peripheral, spinal and supraspinal nociceptive
      pathways and that peripheral afferents may contribute to at-level neuropathic
      pain after spinal cord injury in this patient. Lesioned peripheral afferents in
      combination with central neuronal hyperexcitability are discussed as a likely
      underlying pain mechanism.

PMID- 17509763
TI  - The inventory of parent/caregiver responses to the children's pain experience
      (IRPEDNA): development and preliminary validation.
AB  - This paper describes the development and preliminary validation of a self
      administered instrument designed to measure parents/caregivers' responses to
      children's pain episodes. For empirical validation purposes, a 60-item inventory
      was answered by 401 adults whose children's ages ranged from 6 to 16 years
      (mean=10.44, and SD=2.25 years). Factor structure and item analyses led to a 37
      item inventory with three interrelated scales, namely: solicitousness (n=15
      items), discouragement (n=10 items), and promotion of well-behaviors and coping
      (n=12 items). The three scales had good internal consistency, with coefficient
      alphas of 0.87, 0.83 and 0.87, respectively; they also showed good criterion
      related validity.

PMID- 17509764
TI  - Energy-filtered electron backscatter diffraction.
AB  - The electron backscatter diffraction (EBSD) analytical technique is invaluable
      for determining the crystallography of bulk alloys, thin films, and
      nanoparticles. However, our physical understanding of EBSD pattern generation is
      incomplete, which hinders our ability to push the limits of EBSD analysis. Here,
      using an energy filter with better than 10 eV resolution, we experimentally
      demonstrate the energy dependence of EBSD patterns from elements over a large
      atomic number range. We verify that low-loss electrons are the major contributors
      to EBSD patterns, but that there is still a diffraction contribution from
      electrons with only 80% of the incident beam energy. Additionally, the bands in
      filtered EBSD patterns have contrast that is more than twice the contrast of
      their unfiltered counterparts. The band contrast reaches a maximum for a cutoff
      energy in the filter of about 3% below the energy of the incident beam. Different
      mechanisms are used to explain the drop in contrast on each side of the maximum.
      With the cutoff set very close to the energy of the incident beam, the patterns
      become more blurred. We used a Monte Carlo simulation in the analysis of these
      experiments.

PMID- 17509765
TI  - Imaging of radiation-sensitive samples in transmission electron microscopes
      equipped with Zernike phase plates.
AB  - We have optimized a bright-field transmission electron microscope for imaging of
      high-resolution radiation-sensitive materials by calculating the imaging dose
      n(0) needed to obtain a signal-to-noise ratio (SNR)=5. Installing a Zernike phase
      plate (ZP) decreases the dose needed to detect single atoms by as much as a
      factor of two at 300 kV. For imaging larger objects, such as Gaussian objects
      with full-width at half-maximum larger than 0.15 nm, ZP appears more efficient in
      reducing the imaging dose than correcting for spherical aberration. The imaging
      dose n(0) does not decrease with extending of chromatic resolution limit by
      reducing chromatic aberration, using high accelerating potential (U(0)=300 kV),
      because the image contrast increases slower than the reciprocal of detection
      radius. However, reducing chromatic aberration would allow accelerating potential
      to be reduced leading to imaging doses below 10 e(-)/A(2) for a single iodine
      atom when a CS-corrector and a ZP are used together. Our simulations indicate
      that, in addition to microscope hardware, optimization is heavily dependent on
      the nature of the specimen under investigation.

PMID- 17509766
TI  - Failure of Duddingtonia flagrans to reduce gastrointestinal nematode infections
      in dairy ewes.
AB  - A field study was conducted on three Swiss farms to investigate the efficacy of
      Duddingtonia flagrans against naturally acquired infections of gastrointestinal
      nematodes in adult dairy sheep. On each farm the ewes were divided into two equal
      groups. One group received Duddingtonia during a period of 4 months at a daily
      dose rate of 10(6) chlamydospores per kilogram body weight, the second group
      acted as controls. At an overall moderate infection level in all farms D.
      flagrans did not have a significant effect on the observed parasitological
      parameters with the exception of a significantly reduced herbage infectivity in
      one farm. In contrast, the results from faecal cultures indicated a mean
      suppression of larval development during the fungus-feeding period between 82, 89
      and 93% on the three farms, respectively. The discrepancy observed between the
      fungus efficacy in coprocultures and on pasture, which was also observed in
      several other studies deserves further research.

PMID- 17509767
TI  - P2 purinoceptor antagonists inhibit the non-adrenergic, non-cholinergic
      relaxation of the human colon in vitro.
AB  - Neurotransmitters released by myenteric neurons regulate movements of intestinal
      smooth muscles. There has been little pharmacological evidence for a role of
      purinergic mechanisms in the non-adrenergic, non-cholinergic (NANC) relaxation of
      the human large intestine. We used P(2) purinoceptor antagonists to assess
      whether such receptors are involved in the NANC relaxation of the circular muscle
      of the human sigmoid colon. It was also investigated whether the guanylate
      cyclase enzyme mediates the NANC response. Human colonic circular strips were
      tested in organ bath experiments with isotonic recording. NANC, non-nitrergic
      relaxations induced by electrical field stimulation (1 and 10 Hz, in the presence
      of atropine, guanethidine, and 100 microM N(G)-nitro-L-arginine [L-NOARG]) were
      strongly inhibited by a combination of the P(2) purinoceptor antagonists
      pyridoxal-phosphate-6-azophenyl-2',4'-sulfonic acid (PPADS) (50 microM) and
      suramin (100 microM). PPADS plus suramin was ineffective in the absence of L
      NOARG. L-NOARG alone significantly reduced the NANC relaxation to electrical
      stimulation. PPADS plus suramin strongly inhibited the relaxation in response to
      exogenous alpha,beta-methylene ATP. The guanylate cyclase inhibitor 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (3 microM) inhibited the NANC
      relaxation, but did not add to its reduction by L-NOARG. L-NOARG was still
      slightly effective in the presence of ODQ. Vasoactive intestinal polypeptide
      tachyphylaxis failed to influence the non-nitrergic NANC relaxation. It is
      concluded that nitric oxide (NO) and ATP co-mediate, in a non-additive manner,
      the NANC relaxation. NO probably acts through the guanylate cyclase, though a
      small fraction of its effect might be mediated by other mechanisms. Activators of
      the guanylate cyclase other than NO do not seem to participate in the NANC
      relaxation.

PMID- 17509768
TI  - Expression of the N-methyl-D-aspartate receptor NR1 splice variants and NR2
      subunit subtypes in the rat colon.
AB  - N-methyl-D-aspartate (NMDA) receptors and the expression of their different
      splice variants and subunits were previously characterized in the brain and
      spinal cord. However, knowledge on the NMDA receptor expression and function in
      the enteric nervous system is limited. Previous work suggested that NMDA
      receptors were involved in a rat model of visceral hypersensitivity. The aim of
      this study was to characterize the expression of the NMDA receptor NR1 splice
      variants and the NR2 subunit subtypes in the rat colon. We visualized the
      expression of NR1 protein in the rat submucosal and myenteric plexuses. The NR1
      splice variants found in the colon of rats lacked the N1 and C1 cassettes and
      contained the C2 and C2' cassettes (NR1(000) and NR1(001)). The NR2B and NR2D
      subunits were also found in the rat colon. Moreover, NMDA receptors in the rat
      colon were heteromeric, since NR1 was co-localized with NR2B and NR2D subunits
      using fluorescent immunohistochemistry. The identification of the NMDA receptors
      in the enteric nervous system could lead to the development of drugs that
      selectively modulate bowel function.

PMID- 17509769
TI  - Effects of sex and APOE epsilon4 on object recognition and spatial navigation in
      the elderly.
AB  - To determine effects of APOE epsilon4 (epsilon4) on cognitive performance of
      healthy elderly, 116 nondemented elders (mean age 81 years) were cognitive
      tested. The established tests Faces, Family Pictures, Spatial Span Forward and
      Backward, and the object recognition and spatial navigation tests developed in
      our laboratory were used as cognitive tests. Salivary samples were collected to
      determine APOE genotype and salivary testosterone and cortisol levels. Non
      epsilon4- and epsilon4-carrying men and women did not differ in age, Mini-Mental
      State Examination, Wide Range Achievement Test-Reading, Beck Anxiety Inventory,
      or reaction time scores. There was an effect of epsilon4 on the object
      recognition and spatial navigation tests, with non-epsilon4 carriers
      outperforming epsilon4 carriers, but not in the other cognitive tests. No
      relationship was found for sex and epsilon4 status or sex and performance during
      the hidden session of Memory Island. In men, salivary cortisol levels correlated
      with object recognition. These results show that object recognition and spatial
      navigation tests are useful to assess cognitive function in the elderly.

PMID- 17509770
TI  - Adolescent smoking networks: the effects of influence and selection on future
      smoking.
AB  - Peer influence and peer selection have both been linked to the smoking behavior
      of adolescents. The present investigation uses social network analysis
      methodology to explore the simultaneous effects of both processes on adolescent
      smoking and smoking susceptibility over two time periods. Results suggest the
      effects of friendship selection in 6th grade on smoking behavior in 7th grade
      were primarily direct. Selecting smokers as friends in 6th grade predicted both
      smoking and smoking susceptibility in 7th grade, and selecting susceptibles
      predicted future friendship selection and peer influence. Influence processes
      were indirectly related to smoking. Smokers' influence in 6th grade predicts the
      selection of smokers as friends in 7th grade. Smokers' influence also
      demonstrated a protective effect when ties were not reciprocated.

PMID- 17509771
TI  - Keloids: A viral hypothesis.
AB  - The triggering cause of keloid formation on a healing wound remains an enigma. In
      fact, the hypotheses put forward so far to explain this phenomenon seem
      inconsistent with some clinical features of the disease. The recently established
      bonds between infectious agents and some pathologies of unknown origin such as
      peptic ulcer disease, Kaposi's sarcoma or cervical cancer among others led us to
      consider a potential infectious origin for keloids. This paper presents an
      infection-based hypothesis (specifically, a viral hypothesis) intended to account
      for most of their clinical features. Essentially, we hypothesize that healthy
      individuals carrying a virus, whether known or unknown, associated to some
      adjuvant, and having some genetic susceptibility, may develop keloids during the
      scar maturation process in the following manner: the virus would make the bone
      marrow or lymphatic system its reservoir, residing there in a silent state, and
      reach the wound via two different mechanisms. The primary mechanism might use an
      internal circuit through which the viral genome would be transported from its
      myeloid reservoir to the wound via bone marrow or circulating fibrocytes
      chemotactically attracted to the damaged skin region. The secondary mechanism
      might involve an external circuit by which infecting virions via saliva would be
      shed in the wound directly (preferentially in the sternal or deltoid region) or
      indirectly (other satellite regions) via the hands or some fomites. A combination
      of both mechanisms might also be possible. Once in the wound, the virus would
      switch from a silent state to a latent state by effect of some chemical stimulus
      probably generated during the tissue repair process; in the new state, the
      transcription of some of the powerful viral proteins might cause thorough
      derailment of the normal repair process. As a result, keloid growth might depend
      both on individual susceptibility and on the viral load deposited into the wound;
      the greater the susceptibility and viral load were, the more markedly the keloid
      would develop and the more aggressive it would be.

PMID- 17509772
TI  - A new prognostic marker for obstructive sleep apnea: hepcidin.

PMID- 17509773
TI  - Adiponectin: saving the starved and the overfed.
AB  - The incidence of the metabolic syndrome, type 2 diabetes and cardio- and
      cerebrovascular disease is increasing in the Western world. The adipocyte derived
      protein adiponectin is thought to have a protective role against these
      conditions. But why is it so? Is it reasonable to believe that we have
      adiponectin to gain protection from welfare related diseases? Humans have had a
      far deadlier foe throughout history than obesity and sedentariness and that is
      starvation. During starvation, the body is catabolic in order to provide fuel.
      Catabolism is also seen in patients with advanced cardiac or renal failure, type
      1 diabetes and anorexia. These subjects have higher adiponectin levels than
      controls. In this article, I will put forward the hypothesis that the adiponectin
      system evolved in order to help us to survive periods of malnourishment.

PMID- 17509774
TI  - Reactive oxygen species in cancer, too much or too little?
AB  - It is widely accepted that increased levels of reactive oxygen species (ROS)
      contribute to carcinogenesis. However, this claim has not been confirmed by
      experiments. On the contrary, a growing number of studies clearly demonstrate
      that ROS are normal cellular signals and induce cell differentiation and
      apoptosis, the opposite processes to cancer, which is dedifferentiated. Thus, it
      is hypothesized here that decreased levels of ROS may lead to cancer development,
      which is supported by following observations: (1) the fast-growing tumor produces
      ROS at a rate only one-third of the rate found with the control liver
      mitochondria; (2) the reduction in tumor mitochondrial content indicates low
      level of ROS production; (3) the low levels of manganese superoxide dismutase in
      tumor mitochondria also indicate decreased production of ROS, because the enzyme
      activity is induced by ROS; (4) lipid peroxidation capacity was decreased in
      human colon carcinomas and Yoshida hepatomas; (5) low levels of lipid
      peroxidation de-inhibit glucose-6-phosphate dehydrogenase, whose activity is
      always increased in a variety of cancers without exception. Clarification of real
      role of ROS in cancer may shed light on the understanding of how impairment of
      mitochondria leads to malignant transformation of normal cells, and offer new
      types of strategies for cancer prevention and therapy.

PMID- 17509775
TI  - Human embryonic stem cell research and self evolution.

PMID- 17509776
TI  - Helicobacter pylori alters the distribution of ZO-1 and p120ctn in primary human
      gastric epithelial cells.
AB  - Helicobacter pylori infection is related to the development of diverse gastric
      pathologies, possibly by affecting epithelial junctional complexes that define
      cell polarity and play an essential role in transepithelial transport and cell
      cell adhesion. Using primary gastric epithelial cell cultures, effects of H.
      pylori on the expression and localization of tight/adherence junction proteins
      and the resulting morphological changes and migratory capabilities were studied
      under in vivo-like conditions. Gastric epithelial cells were isolated from
      biopsies or gastrectomies and maintained in Quantum286 on collagen I-coated
      culture dishes or cover-slips. Cell cultures were characterized and further
      analyzed by western blot and immunofluorescent staining for ZO-1, p120ctn, and H.
      pylori CagA. Morphological changes and migratory response were monitored by time
      lapse digital image microscopy. ZO-1 and p120ctn protein expression levels remain
      unaffected by H. pylori infection. Immunocytochemistry on H. pylori-infected
      primary cell monolayers focally showed disruption of intercellular ZO-1 staining
      and accumulation of ZO-1 in small vesicles. H. pylori infection recruited non
      phosphorylated p120ctn to perinuclear vesicles. The fraction of phosphorylated
      p120ctn increased and could be detected in the nucleus, at the cell membrane, and
      at the leading edge of migrating cells. These alterations, triggered by H. pylori
      infection, are associated with an elongation phenotype and increased migration.

PMID- 17509777
TI  - Epoxysesquithujene, a novel sesquiterpenoid from Valeriana hardwickii var.
      hardwickii.
AB  - Epoxysesquithujene, a new sesquiterpene epoxide has been characterized in the
      essential oil of Valeriana hardwickii var. hardwickii on the basis of chemical
      reactions and extensive NMR data. Fourteen other terpenoids have also been
      identified on the basis of GC-MS.

PMID- 17509778
TI  - The molecular heterogeneity of hemocyanin: Structural and functional properties
      of the 4x6-meric protein of Upogebia pusilla (Crustacea).
AB  - The structural properties of the hemocyanin isolated from the Mediterranean mud
      shrimp, Upogebia pusilla (Decapoda: Thalassinidea), were investigated. Our intent
      was to make use of the U. pusilla case to perform a structural comparison between
      crustacean and chelicerate 4x6-meric hemocyanins. The thalassinidean hemocyanin
      appears similar in size but different in structural organization compared to the
      chelicerate 4x6-mer. Ultracentrifuge analyses on the purified protein revealed a
      sedimentation coefficient of 39S, typical of 4x6 hemocyanins. Electron
      micrographs are in agreement with a model in which four 2x6-meric building blocks
      are arranged in a tetrahedron-like quaternary structure and not in the quasi
      square-planar orientation characteristic of the chelicerate protein. Size
      exclusion chromatography-fast protein chromatography analysis showed elevated
      instability of the protein in absence of divalent ions or at pH values higher
      than 8.0. This analysis also shows that the dissociation of the U. pusilla 4x6
      meric hemocyanin into hexamers occurs without any intermediate 2x6-meric state,
      in contrast with the dissociation profile of the chelicerate protein exhibiting
      several dissociation intermediates. The oxygen-binding properties of U. pusilla
      hemocyanin were studied to disclose possible effects by the typical allosteric
      effectors that modulate the functional properties of crustacean hemocyanin. A
      marked Bohr and lactate effect, but no significant influence of urate, on the
      oxygen affinity of U. pusilla hemocyanin were found.

PMID- 17509779
TI  - Time course of biofilm formation by Staphylococcus aureus and Staphylococcus
      epidermidis mastitis isolates.
AB  - Biofilm formation is considered a selective advantage for staphylococci mastitis
      isolates, facilitating bacterial persistence in the udder. It requires attachment
      to mammary epithelium, proliferation and accumulation of cells in multilayers and
      enclosing in a polymeric matrix, being regulated by several loci. As biofilm
      formation can proceed through different pathways and time ranges, its detection
      may differ according to the time of observation. This study aimed at evaluating
      the time course evolution of biofilm production in Staphylococcus aureus (n = 26)
      and Staphylococcus epidermidis (n = 29) mastitis isolates by Fluorescent In Situ
      Hybridisation. Biofilm-forming ability increased with incubation time for both
      species: for S. aureus, 34.6%, 69.2% and 80.8% of the isolates were able to
      produce biofilm at 24, 48 and 72 h, respectively. For S. epidermidis, 44.8%,
      62.1% and 75.9% of the isolates were biofilm-positive at 24, 48 and 72 h,
      respectively. No significant difference was found between species at each time
      point (Friedman's test, p > 0.05). For S. aureus, although a significant
      difference was found between 24 and 48 h (Wilcoxon matched paired test, p <
      0.05), no significant difference was found between 24 and 48 h (p > 0.05). For S.
      epidermidis, significant differences were found between each time point (p <
      0.05). Bacterial biofilms may impair eradication of chronic mastitis, rendering
      antibiotherapy less effective. Detection of biofilm-forming ability in mastitis
      isolates may provide useful information for the establishment of a more adequate
      therapeutic regimen, in view of the antimicrobial concentrations required for
      bacterial control. However, it is essential that biofilm formation time course is
      taken into consideration.

PMID- 17509781
TI  - Apoptosis induction on human hepatoma cells Hep G2 of decabrominated diphenyl
      ether (PBDE-209).
AB  - Polybrominated diphenyl ethers (PBDEs) are an important class of halogenated
      organic brominated flame retardants. Because of their presence in abiotic and
      biotic environments widely and their structural similarity to polychlorinated
      biphenyls (PCBs), concern has been raised on their possible adverse health
      effects to humans. This study was designed to determine the anti-proliferative,
      apoptotic properties of decabrominated diphenyl ether (PBDE-209), using a human
      hepatoma Hep G2 line as a model system. Hep G2 cells were cultured in the
      presence of PBDE-209 at various concentrations (1.0-100.0 micromol/L) for 72 h
      and the percentage of cell viability was evaluated by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The results showed that PBDE
      209 inhibited the cells viability in time and concentration-dependent
      characteristics at concentrations (10.0-100.0 micromol/L). We found that anti
      proliferative effect of PBDE-209 was associated with apoptosis on Hep G2 cells by
      determinations of morphological changes, cell cycle and apoptosis. Mechanism
      study showed that PBDE-209 could increase the generation of intracellular
      reactive oxygen species (ROS) concentration-dependently. Antioxidant N
      acetylcyteine partially inhibited the increase of ROS. The mechanism for its
      hepatoma-inhibitory effects was the induction of cellular apoptosis through ROS
      generation. In addition, activity of lactate dehydrogenase (LDH) release
      increased when the cells incubated with PBDE-209 at various concentrations and
      times. These results suggested that PBDE-209 had the toxicity activity of anti
      proliferation and induction of apoptosis in tumor cells in vitro.

PMID- 17509780
TI  - Genetic and antigenic characterization of bovine viral diarrhea virus type 2
      isolated from Indian goats (Capra hircus).
AB  - Recent studies have shown that bovine viral diarrhea virus (BVDV) type 1 is
      widely prevalent in Indian cattle. In a surveillance of randomly collected 562
      blood samples from seven states during 2004-2006, BVDV type 2 was detected in two
      native Indian goats by nested reverse transcription polymerase chain reaction
      (nRT-PCR). The virus isolated from them was classified antigenically as BVDV 2 on
      the basis of virus neutralization test and reactivity with monoclonal antibodies.
      Phylogenetic analysis of three different genomic regions, 5' un-translated region
      (5' UTR), E(rns) structural coding region and NS5B nonstructural coding region
      typed Indian goat isolate as BVDV 2a having close similarity with strains from
      North America and Europe suggesting its probable introduction through trade. It
      was placed in a separate clade within the 2a branch having unique mutations in
      E(rns) and NS5B region. This is the first report of BVDV 2 in India and only
      second time recorded in goat species. The isolation of BVDV 2 from goat warrants
      intensive surveillance in cattle and sheep.

PMID- 17509782
TI  - Characterization and relevance of physicochemical interactions among components
      of a novel multiparticulate formulation for colonic delivery.
AB  - The primary objective of this study was to investigate potential interactions
      among a model drug (azathioprine; AZA), polymers and a divalent metal ion, which
      were utilized in the development of a novel multiparticulate formulation for
      colonic delivery. The approach involved preparation of beads by ionotropic
      gelation of deacylated gellan gum (DGG) in the presence of Ca(2+) ions, followed
      by coating with Eudragit S-100. Various possible physicochemical interactions
      among formulation components were characterized by DSC, FT-IR, XRPD, (1)H-NMR,
      and an isothermal stress test. Results of isothermal stress testing indicated
      that there was no significant interaction of AZA with DGG and Eudragit S-100.
      However, results of DSC and XRPD studies suggested that there could be
      interactions between AZA and DGG, and ionotropic gelation can affect the physical
      state of AZA, which may have implications for drug release characteristics and,
      physical and chemical stability. The results of FT-IR studies were suggestive of
      interactions of DGG with AZA and Eudragit S-100, and provided evidence for
      interactions of AZA and DGG with Ca(2+) ions. The electrostatic interaction of
      DGG with Ca(2+) was also supported by results of DSC studies while that between
      AZA and Ca(2+) was confirmed by (1)H-NMR studies. This study, to our knowledge,
      is first reported investigation in which the unique thermal property of gellan
      gum gels, and possible interactions between a drug and counter ions of an
      ionotropic agent have been demonstrated through bead characterization studies.
      The formation of AZA-Ca(2+) complex could have an impact on drug release
      kinetics, product stability and clinical efficacy for treatment of inflammatory
      bowel diseases or other diseases, which merit further investigation.

PMID- 17509783
TI  - Long term effects of BAPTA in scala media on cochlear function.
AB  - BAPTA was iontophoresed or allowed to diffuse into the scala media of the first
      turn of the guinea pig cochlea via pipettes inserted through the round window and
      basilar membrane. Cochlear action potential (CAP) thresholds for basal turn
      frequencies were elevated, scala media cochlear microphonic in response to a
      207Hz tone were drastically reduced and the distortion products 2f1-f2 and f2-f2
      in response to primaries set at 18 and 21.6kHz were eliminated or severely
      reduced. The animals were recovered and the above measurements repeated between
      24 and 240h after the application of BAPTA. In all animals thresholds for basal
      turn frequencies remained elevated, and the distortion components were severely
      reduced. The endolymphatic potential (EP), measured through the basilar membrane
      on recovery, was not significantly different from the values measured before
      BAPTA was applied. If the effect of BAPTA, in lowering endolymphatic Ca(2+)
      concentration, is restricted to the destruction of tip links, as has been shown
      in many other preparations, then these results suggest that this effect has
      permanent consequences, either because the tip links failed to regenerate or
      because their destruction precipitated the degeneration of OHCs. These results
      may have a bearing on the mechanisms behind permanent threshold shift.

PMID- 17509784
TI  - Palliative total pharyngo-laryngo-esophagectomy.
AB  - OBJECTIVE: To evaluate the outcomes of total pharyngo-laryngo-esophagectomy
      (TPLE) as a palliative procedure for achieving oral intake without tube
      placement. BACKGROUND: Patients with head and neck cancers require airway
      maintenance achieved by the placement of a tracheostomy tube and nutrition
      provided through a gastric fistula or a central vein, which may markedly decrease
      the quality of life (QOL) of the patients. CASES: Two patients with cervical
      esophageal cancer are described. The first patient was a 69-year-old male with
      cervical esophageal cancer with vertebral invasion, for which complete resection
      was not possible. Following TPLE, oral intake was initiated on post-operative day
      9 and was maintained for 138 days. The second patient was a 73-year-old male with
      recurrent cervical esophageal cancer and unresectable lymph node metastasis for
      which lymph node dissection was not applicable. Following TPLE, oral intake was
      initiated on post-operative day 7 and was maintained for 199 days. Both patients
      were satisfied with the outcome. CONCLUSIONS: The QOL of the two patients was
      improved following the restoration of oral intake ability. Palliative TPLE may be
      appropriate for patients with advanced head and neck cancers.

PMID- 17509785
TI  - [Pseudomonas and bronchial diseases].
AB  - The risk of Pseudomonas aeruginosa (Pa) acquisition, colonization, and infection
      during chronic bronchial disease varies according to the disease (cystic
      fibrosis, bronchial dilatation, post-tobacco abuse chronic obstructive
      bronchopneumonia), its evolutive stage, and a number of known or suspected
      factors. The involvement of Pa marks an important evolution of the disease, well
      demonstrated in cystic fibrosis. P. aeruginosa can adhere to epithelial cells
      (initial colonization) then organizes itself in complex structures evolving from
      simples microcolonies to macrocolonies in a structured biofilm supporting chronic
      colonization. P. aeruginosa can produce several factors of virulence, leading to
      the permanent destruction of host cells, thus inducing the regular liberation of
      pro-inflammatory mediators implementing a vicious circle worsening these chronic
      respiratory diseases and favoring their exacerbation. Chronic Pa suppuration has
      a systemic impact and justifies a global multidisciplinary management. In cystic
      fibrosis, the presence of P. aeruginosa is a major prognostic element. The
      current consensus is to detect the primary colonization as early as possible
      eradication is still possible and to treat it before it evolves to chronicity.
      But right now, this type of management has not been justified for other chronic
      bronchial diseases.

PMID- 17509786
TI  - A simplified formula for T1 contrast optimization for short-TR steady-state
      incoherent (spoiled) gradient echo sequences.
AB  - There are certain instances in practical magnetic resonance imaging where T1
      changes by a small amount relative to a neighboring pixel or between scans for a
      given pixel. The source of these small changes in T1 can be caused either by
      changes in tissue water content or by the uptake of a contrast agent. For short
      repetition time (TR) spoiled gradient echo imaging, we show that a robust and a
      simple, easy to use back-of-the-envelope expression for the flip angle that
      optimizes contrast under these conditions is given by radical 3theta E in radians
      or (180/pi) radical6TR/T1 in degrees. We show that for a TR/T1 ratio of up to 0.3
      and for a T1 change of up to +/-50%, this approximation to the optimal flip angle
      produces a contrast to within 6% of the theoretical maximum value and that these
      predictions are in good agreement with experiment.

PMID- 17509787
TI  - Independent component analysis in the presence of noise in fMRI.
AB  - A noisy version of independent component analysis (noisy ICA) is applied to
      simulated and real functional magnetic resonance imaging (fMRI) data. The noise
      covariance is explicitly modeled by an autoregressive (AR) model of order 1. The
      unmixing matrix of the data is determined using a variant of the FastICA
      algorithm based on Gaussian moments. The sources are estimated using the
      principle of maximum likelihood by modeling the source densities as asymmetric
      exponential functions. Effect of dimensionality reduction on the effective noise
      covariance used, accuracy of the obtained mixing matrix and degree of improvement
      in estimating fMRI sources are investigated. The primary conclusions after using
      this method of evaluation are as follows: (a) weighting matrix estimates are
      similar for noisy and conventional ICA in the realm of typical fMRI data, and (b)
      source estimates are improved by 5% (as measured by the correlation coefficient)
      in realistic simulated data by explicitly modeling the source densities and the
      noise, even when just a simple white noise model is used.

PMID- 17509788
TI  - Prosthetic hip infection due to Brucella melitensis: case report and literature
      review.
AB  - Prosthetic joint infection (PJI) due to Brucella spp. is extremely rare. We
      report the case of a prosthetic hip infection due to Brucella melitensis in a 51
      year-old male patient. The initial presentation was a gluteal abscess. There was
      radiographic evidence of implant loosening. The patient was cured after prolonged
      treatment with streptomycin, rifampicin, and doxycycline, followed by 2-stage
      exchange of the prosthesis. Brucella spp. should be considered in the
      differential diagnosis of PJI in countries where brucellosis is endemic. The
      review of all cases previously reported shows that a conservative approach using
      antibiotics alone can be followed in patients without signs of implant loosening.
      In contrast, prolonged antibiotic treatment and prosthetic joint revision should
      be considered in patients with evidence of implant loosening.

PMID- 17509789
TI  - Bowel colonization with vancomycin-resistant enterococci after antimicrobial
      therapy for intra-abdominal infections: observations from 2 randomized
      comparative clinical trials of ertapenem therapy.
AB  - The impact of different antimicrobial regimens for intra-abdominal infections on
      the frequency of bowel colonization with vancomycin-resistant enterococci (VRE)
      was examined in 2 randomized open-label trials of intra-abdominal infection
      comparing piperacillin-tazobactam or ceftriaxone/metronidazole with ertapenem. In
      these short-term studies, overall rates of bowel colonization with VRE were
      generally comparable after treatment with piperacillin-tazobactam,
      ceftriaxone/metronidazole, or ertapenem.

PMID- 17509790
TI  - Pyrosequencing of a recA gene variable region for Burkholderia cepacia complex
      genomovar identification.
AB  - We developed an assay to identify Burkholderia cepacia complex genomovars by
      Pyrosequencing of a variable recA gene segment. Fifteen reference strains and 30
      clinical isolates of B. cepacia complex were sequenced. Full 77-base pair target
      sequences were obtained from 44 of the 45 isolates, and BLAST queries of the
      sequences correctly identified the genomovar of these 44 isolates. Three
      Burkholderia multivorans isolates were identified as B. multivorans/Burkholderia
      ambifaria, indicating that additional identification methods may be needed for
      some B. multivorans strains.

PMID- 17509791
TI  - Multilocus sequence typing of Candida tropicalis shows clonal cluster enriched in
      isolates with resistance or trailing growth of fluconazole.
AB  - Multilocus sequence typing (MLST) was used to characterize the genetic profiles
      of 52 Candida tropicalis isolates collected from 10 hospitals in Taiwan. A total
      of 33 diploid sequence types (DSTs) were differentiated among the 52 isolates and
      all were novel to the Internet C. tropicalis DST database
      (http://pubmlst.org/ctropicalis/). Eleven (33.3%) of the 33 DSTs could be
      assigned to 3 major clonal clusters (1-3) based on eBURST calculation. Only
      clonal cluster 1 co-clustered isolates from UK and the United States. Clonal
      cluster 2 was enriched with isolates with resistance or trailing growth of
      fluconazole (14/20, 70%). Furthermore, there are a number of pulsed-field gel
      electrophoresis subtypes associated with the isolates in this cluster,
      demonstrating that possibly more than one clone with resistant or trailing
      property have emerged and spread in Taiwan in 1999.

PMID- 17509792
TI  - Pathogenic and molecular characterization of the H5N1 avian influenza virus
      isolated from the first human case in Zhejiang province, China.
AB  - Since the reemergence of highly pathogenic avian influenza virus H5N1, it caused
      disease in 20 people with 13 deaths in mainland of China. On February 21, 2006,
      the first suspected human case in Zhejiang province was reported. Pathogenic
      analyses, including reverse transcriptase polymerase chain reaction (RT-PCR),
      real-time RT-PCR, and virus isolation, were carried out to confirm the pathogen
      from tracheal aspirate specimen. In addition, antibody in serum sample was
      detected using hemagglutination-inhibition (HI). Results revealed that nucleic
      acid extracted from the tracheal aspirate specimen was positive for H5N1 avian
      influenza virus and influenza virus type A. The H5N1 virus strain named
      A/Zhejiang/16/06 (H5N1) was isolated. The titers of HI antibody for H5N1 avian
      influenza virus were 1:320 and 1:640, respectively. The sequenced genes were all
      avian origin. Phylogenetic analyses between the A/Zhejiang/16/06 and other H5N1
      influenza viruses were also included.

PMID- 17509793
TI  - Breast and osteoarticular tuberculosis in a male patient.
AB  - Breast tuberculosis is an uncommon illness. It is predominant in young women. To
      our knowledge, only 7 cases of tuberculous mastitis in men have been reported in
      the English literature since 1945. Furthermore, there are no male patients who
      have breast and osteoarticular tuberculosis in the literature. We presented a 41
      year-old man who was admitted with a fixed tender mass in the right retromammary
      region and pain in the right hip. Mycobacterium tuberculosis colonies were
      isolated from the semisolid mass of breast. Histopathologic examination revealed
      caseous granulomatous infection in the right hip synovial tissue. He was treated
      successfully with only antituberculous drugs.

PMID- 17509794
TI  - Comparison of culture and 2 real-time polymerase chain reaction assays to detect
      group B Streptococcus during antepartum screening.
AB  - Group B Streptococcus (GBS) is the most common cause of life-threatening
      infection in neonates but is preventable if the mother is diagnosed before and
      treated at delivery. Using 200 vaginal-rectal swabs inoculated to enrichment
      (LIM) broths, we compared routine culture and 2 real-time polymerase chain
      reaction (PCR) assays for detection of GBS: the LightCycler (LC) Strep B analyte
      specific reagents (ASRs) (Roche Diagnostics, Indianapolis, IN) and the BD GeneOhm
      StrepB (BD-StrepB) test (BD GeneOhm Sciences, San Diego, CA). Culture detected
      26.5% GBS-positive specimens, whereas the LC Strep B ASR and BD-StrepB test
      identified 29.5% and 30.0% positive specimens, respectively. Because of the
      increased detection rate of 3.0% to 3.5% observed with PCR, a second GBS-specific
      amplicon was sequenced to confirm the presence of GBS that was not detected by
      culture. In our hands, the sensitivity/specificity of the LC Strep B ASR was
      100%/95.9%, and the BD-StrepB test was 92.5%/92.5% using culture as the gold
      standard.

PMID- 17509795
TI  - Serologic and molecular characterization of Pseudomonas aeruginosa Jordanian
      clinical isolates compared with the strains of International Antigenic Typing
      Scheme.
AB  - One hundred clinical isolates of Pseudomonas aeruginosa were serologically
      classified into 7 Jordanian serotypes (labeled JO1-JO7) Odeh, 2002, M.Sc. thesis,
      University of Jordan). Using the slide agglutination test, 4 of them (JO4, JO5,
      JO6, and JO7) were serologically matched with the International Antigenic Typing
      Scheme (IATS) strains (IATS 20, IATS 10, IATS 6, and IATS 11). One serotype (JO1)
      showed a weak cross-reaction with IATS 1. The remaining 2 local serotypes (JO2
      and JO3) did not react with any of the 20 IATS strains. Serologic analysis data
      showed to a certain extent correlations with molecular data using genetic
      clustering and similarity indices generated by random amplified polymorphic DNA
      polymerase chain reaction (RAPD-PCR). Each of the 4 identified local serotypes
      formed a cluster with its serologically matched IATS strain with relatively high
      average similarity indices, whereas lower average similarity index was observed
      between IATS 1 and JO1, in consistence with the weak serologic reaction using the
      slide agglutination test. On the other hand, the 2 nontypeable serotypes (JO2 and
      JO3) formed 2 separate clusters that could not be matched to any of the IATS
      strain. Phenotypic and genotypic analyses suggest that JO2 and JO3, and possibly
      JO1, can be new serotypes of P. aeruginosa. RAPD-PCR was also used to study the
      relative relatedness among the 20 IATS strains. The IATS strains formed 2 main
      clusters. Half of the IATS strains formed one main cluster that included IATS 11
      20. The remaining IATS strains (8 strains) formed the second main cluster, with
      the exception of IATS 4 and 9, where each formed a separate cluster.

PMID- 17509796
TI  - Histoplasmosis diagnosis using a polymerase chain reaction method. Application on
      human samples in French Guiana, South America.
AB  - Untreated histoplasmosis is life threatening, especially in immunosuppressed
      patients. In French Guiana, South America, it is one of the most common
      opportunistic infections in AIDS patients. Twenty-one cases of disseminated
      histoplasmosis were diagnosed in 2004 in the mycology laboratory of Cayenne
      hospital. Culture samples for histoplasmosis diagnosis is simple, sensitive, and
      specific, but it is a lengthy process. Management of the disease is then
      dangerously delayed. In this work, we tested a polymerase chain reaction (PCR)
      method on 40 samples from patients with suspected disseminated histoplasmosis.
      The recently described Hcp100 nested PCR method was used to detect Histoplasma
      capsulatum DNA in these samples. All of the positive cultures for H. capsulatum
      were also positive with PCR method. Tested on other fungi or negative culture, it
      also showed high specificity. Furthermore, it allows treating patients more
      rapidly. Culture remains necessary, but histoplasmosis PCR offers great
      prospects, on a clinical point of view.

PMID- 17509797
TI  - Epidemiology and evolution of genotype and antimicrobial resistance of an
      imported Shigella sonnei clone circulating in central Taiwan.
AB  - Shigella sonnei replaced Shigella flexneri to become the predominant species for
      shigellosis in 2001 to 2003 in central Taiwan. A total of 425 S. sonnei isolates
      collected from 1996 to 2004 were available for characterization by pulsed-field
      gel electrophoresis (PFGE), inter-IS1 spacer typing (IST), and antimicrobial
      susceptibility testing. The results showed that at least 21 IST clones had
      emerged for the S. sonnei infections in 1996 to 2004. Most IST clones lasted for
      a short time; some circulated for 2 to 3 years. An IST1 clone, detected for the
      first time in 2000, was the most prevalent and responsible for the shigellosis
      epidemic in 2001 to 2003. Over 3 years of sustained transmission, the IST1 clone
      evolved into many strains with different PFGE genotypes and antibiograms. The
      ancestor, with a J16N09.0019 PFGE genotype, remained to be the predominant
      circulating strain in the period studied; however, new strains with certain PFGE
      genotypes and antibiograms could become major circulating strains for subsequent
      infections.

PMID- 17509798
TI  - Comparison of several commercial serologic kits and Em18 serology for detection
      of human alveolar echinococcosis.
AB  - The aim of this study was to design the best serologic strategy for diagnosing
      human alveolar echinococcosis (AE) cases in medical laboratory routine
      procedures. By combining 2 screening techniques, indirect hemagglutination with
      Em(2plus)-ELISA and/or recEm18-ELISA, 46 of 47 AE cases were detected. The
      necessary confirmation of results is then obtained by using immunoblot (LDBIO-IB
      and/or recEm18-IB).

PMID- 17509799
TI  - Production of extracellular proteolytic activity by Histoplasma capsulatum grown
      in Histoplasma-macrophage medium is limited to restriction fragment length
      polymorphism class 1 isolates.
AB  - Extracellular proteolytic activity was studied for 28 strains of Histoplasma
      capsulatum var. capsulatum and 2 strains of H. capsulatum var. duboisii. Secreted
      protease activity assessed by skim milk agarose clearance was limited solely to
      H. capsulatum var. capsulatum restriction fragment length polymorphism (RFLP)
      class 1 strains. There was a difference in proteolytic activity levels among
      class 1 strains. Extracellular proteolytic activity was further determined during
      growth of those strains in liquid medium using azodye-impregnated protein
      substrates. In general, the highest activities were measured when azocollagen was
      used, whereas azocasein and azoalbumin were cleaved less efficiently. The
      activity was inhibited by phenylmethylsulfonyl fluoride, 4-(2-aminoethyl)
      benzenesulfonyl fluoride, antipain, and chymostatin, indicating, thereby, the
      presence of chymotrypsin-like serine proteases. Chromatographic analyses as well
      as variable substrate use at different culture times revealed production of at
      least 2 different enzyme pools of the same serine-like protease family. Our
      results demonstrate a distinctive ability of RFLP class 1 isolates to produce and
      secrete serine proteinase-type activity. This peculiarity may be relevant to the
      biology and pathogenesis of this particular clade of H. capsulatum isolates.
      Overall, the feature of extracellular proteolytic activity production enables a
      convenient and unequivocal identification of RFLP class 1 isolates and, thereby,
      can be used in H. capsulatum strain differentiation and typing.

PMID- 17509800
TI  - Performance of Directigen flu A+B enzyme immunoassay and direct fluorescent assay
      for detection of influenza infection during the 2004-2005 season.
AB  - Early diagnosis of influenza infection is needed to optimize the benefit of
      prescribing antiviral drugs. However, the accuracy of rapid tests is highly
      variable. This study evaluated the performance of Directigen flu A+B enzyme
      immunoassay (EIA) and direct fluorescent assay (DFA) during the 2004-2005
      influenza season. Participants with medically attended acute respiratory illness
      were identified through an active surveillance. Consenting patients (n=818) were
      enrolled and cultured for influenza. Physicians ordered a rapid antigen test (EIA
      or DFA) according to their clinical judgment. Physicians ordered rapid tests with
      EIA (n=109), DFA (n=86), or both (n=9) in 204 patients with acute respiratory
      illness who were also cultured for influenza. The EIA detected 18 of 43 influenza
      infections (sensitivity, 42%; 95% confidence interval [CI], 28-57%), whereas DFA
      detected 26 of 38 influenza infections (sensitivity, 68%; 95% CI, 53-81%).
      Compared with culture, specificity of both EIA and DFA was 96%. During the 2004
      2005 influenza season, both the EIA and DFA had low sensitivity and failed to
      detect influenza in many patients.

PMID- 17509801
TI  - Possible recombination and gene adaptation exchanges among clinical echovirus
      strains: crossing the temporal and topological barriers.
AB  - Six echovirus strains belonging to serotypes echovirus 6, 13, and 30 were
      investigated in the present work by sequencing of the whole 2C gene and about 560
      nt of the 5' part of 3-dimensional genomic region. Four of the 6 echovirus
      strains were epidemics, whereas 2 were from sporadic cases. The whole procedure
      was carried out by using nucleotide distance matrices and phylogeny software. The
      sequences obtained strengthen the observation that recent echovirus isolates
      differ significantly from prototype strains in the downstream regions of the
      genome and provides further evidence that nonstructural enterovirus genes are
      ubiquitous and may combine freely adapting genomic sequences that are not
      restricted from the place of isolates' origin. For diagnostic purposes,
      particular emphasis is given on the utility of sequencing downstream genes and
      comparison of them with corresponding genomic regions from enteroviral strains
      that circulated all over the world.

PMID- 17509802
TI  - Genotype distribution of clinical isolates of Trichosporon asahii based on
      sequencing of intergenic spacer 1.
AB  - The sequence polymorphisms of intergenic transcribed spacer and the antifungal
      susceptibility profile of 18 Trichosporon asahii isolates from Spain, Argentina,
      and Brazil together with 43 intergenic transcribed spacer 1 sequences deposited
      in the GenBank were analyzed. Six genotypes were detected instead of 5 genotypes
      described previously. Genotype 1 was the most common found comprising 57.3% of
      all strains, followed by genotype 3 (14.7%) and genotype 5 (13.1%). Spanish
      strains had members in all genotypes except 2, whereas South American isolates
      were grouped with genotypes 1, 3, and 6. Our results indicate that all genotypes
      are present in at least 2 countries suggesting a worldwide distribution. On the
      other hand, genotype 6 was not previously described but was only composed of 2
      South American strains isolated from a subcutaneous abscess and skin. All
      isolates showed amphotericin B MICs>or=2 mg/L supporting the in vitro resistance
      of this species to this antifungal. Three isolates from South America showed high
      MICs to all antifungals analyzed. The true epidemiologic usefulness of
      classifying T. asahii in genotypes should be ascertaining analyzing a high number
      of isolates from many countries.

PMID- 17509803
TI  - A comparison of the activity of tigecycline against multiresistant clinical
      isolates of Staphylococcus aureus and Streptococcus agalactiae.
AB  - We evaluated the activity of several antibiotics against 225 clinical isolates of
      Staphylococcus aureus and 252 isolates of Streptococcus agalactiae. Only
      tigecycline, glycopeptides, and linezolid were active against all the isolates of
      S. aureus, whereas the beta-lactams were also active against S. agalactiae.
      Tigecycline could be a good alternative to ampicillin in the treatment of group B
      Streptococcus infections in patients allergic to beta-lactam.

PMID- 17509804
TI  - Antimicrobial phenotypes and molecular basis in clinical strains of Clostridium
      difficile.
AB  - Clostridium difficile remains the leading cause of nosocomial-acquired diarrhea.
      This study investigated antimicrobial susceptibility patterns of C. difficile
      over a 3-year period. Three hundred seventeen C. difficile isolates recovered
      between 2002 and 2004 were analyzed for their susceptibility to erythromycin
      (ERY), clindamycin (CLI), moxifloxacin (MXF), doxycycline (DOX), vancomycin
      (VAN), and metronidazole (MTR) by Etest. The molecular basis for resistance was
      investigated using polymerase chain reaction (PCR) and DNA sequencing. PCR
      ribotyping was used to differentiate strains. All strains were susceptible to VAN
      and MTR. Resistance rates to ERY/CLI, MXF, and DOX increased during the study
      period. Eighty-four (26.5%) strains exhibited resistance against ERY/CLI, MXF,
      and DOX. Prevalence of resistance genes was as follows: ermB, 83; ermQ, 0; ermFS,
      1; tetM, 84; tetP, 0; tetO, 2; and gyrA mutation, 76. These results indicate an
      increasing trend in the prevalence of combined resistance against macrolide
      lincosamide-streptogramin B antibiotics, fluoroquinolones, and tetracycline in C.
      difficile. The lack of understanding of antibiotic resistance mechanisms in C.
      difficile and the increased resistant strains warrants further investigations.

PMID- 17509805
TI  - Correlation between early clinical response after catheter removal and diagnosis
      of catheter-related bloodstream infection.
AB  - We conducted a retrospective post hoc analysis of prospectively collected data of
      cancer patients with central venous catheters (CVCs) who developed bacteremia
      with positive quantitative blood cultures (QBCs) drawn simultaneously through
      peripheral vein and CVC and which grew the same microorganisms from both blood
      cultures. We investigated whether clinical response of bacteremia, within 24, 48,
      or 72 h post-CVC removal, could be diagnostic of catheter-related bloodstream
      infection (CRBSI) when compared with microbiologic methods. Clinical response to
      antimicrobial therapy within 24 h of CVC removal in a patient with bacteremia was
      found to be highly suggestive of CRBSI, a finding that correlated well with
      semiquantitative catheter cultures and differential QBCs. However, response to
      antimicrobial therapy at >or=48 h after CVC removal was less likely to be
      diagnostic of CRBSI and could reflect a response to antimicrobial therapy
      irrespective of the source of the bloodstream infections.

PMID- 17509806
TI  - The dense granule protein GRA2, a new marker for the serodiagnosis of acute
      Toxoplasma infection: comparison of sera collected in both France and Iran from
      pregnant women.
AB  - GRA2 is a highly immunogenic protein secreted from the dense granules of
      Toxoplasma gondii. Recent success in purifying full-length, soluble GRA2 from
      bacteria as a thioredoxin (TRX)-(Hisx6) fusion protein led to investigate the
      antigenicity of the recombinant protein against human sera. On immunoblots, TRX
      (Hisx6)-GRA2 was recognized by sera collected in Iran from T. gondii-infected
      pregnant women. An IgG enzyme-linked immunosorbent assay was developed to
      evaluate the reactivity of sera, collected from pregnant women both in France and
      Iran, to the TRX-(Hisx6)-GRA2 fusion protein. Specificity of the test was 96.4%.
      Sensitivity of the GRA2 enzyme-linked immunosorbent assay ranged from 95.8% (sera
      collected in France) to 100% (sera collected in Iran) for sera of acute infection
      and from 65.7% (sera collected in France) to 71.4% (sera collected in Iran) for
      sera of chronic infection. The recombinant GRA2 could thus advantageously
      complement previously described T. gondii antigens for the serodiagnosis of acute
      Toxoplasma infection.

PMID- 17509807
TI  - A structural equation modeling approach to the concepts of adherence and
      readiness in antiretroviral treatment.
AB  - OBJECTIVE: The objective of this secondary analysis of data from a cross
      sectional, nation-wide survey, was to test a hypothesized model with two latent
      concepts (readiness and adherence), based on the theory of trigger events. A
      secondary objective was to compare this model with two simpler models, without
      the concept of readiness. METHODS: Data consisted of a consecutive sample of 828
      HIV patients > or = 18 years on antiretroviral treatment at 30 out of 32 HIV
      Clinics in Sweden (response rate 97.5%). Structural equation modeling (SEM) was
      used to test the models against the empirical data. Chi2 test was used to compare
      fit between models. RESULTS: The hypothesized model, with two latent concepts
      (readiness and adherence), fitted the data best (chi(2)=223.508, d.f.=129, p
      value<0.0001, GFI=0.970, CFI=0.913, RMSEA=0.030), and significantly better than
      the models with adherence as the only latent concept. CONCLUSION: Although the
      SEM technique could not rule out that other models might also fit the data
      equally well, the hypothesized model, where readiness and adherence were two
      separate latent concepts, fitted data the best. This supports readiness as a
      distinct factor that influences adherence and hence treatment outcome. Increased
      attention should therefore be attached to interventions that focus on the
      individual' readiness for behavioural change, i.e. factors amendable to change
      and that can be addressed by the patients themselves. PRACTICE IMPLICATIONS:
      Based on these results it seems necessary to shift focus from adherence to
      readiness, especially in conditions where treatment can be postponed such as
      antiretroviral treatment.

PMID- 17509808
TI  - The effects of a shared decision-making intervention in primary care of
      depression: a cluster-randomized controlled trial.
AB  - OBJECTIVE: Patient-centred depression care approaches should better address
      barriers of insufficient patient information and involvement in the treatment
      decision process. Additional research is needed to test the effect of increased
      patient participation on outcomes. The aim of this study was to assess, if
      patient participation in decision-making via a shared decision-making
      intervention leads to improved treatment adherence, satisfaction, and clinical
      outcome without increasing consultation time. METHODS: Cluster-randomized
      controlled intervention study based on physician training and patient-centered
      decision aid compared to usual care in primary care settings in Sudbaden region
      of Germany. Twenty-three primary care physicians treating 405 patients with newly
      diagnosed depression were enrolled. Patient involvement was measured with the
      patient perceived involvement in care scale (PICS) and a patient participation
      scale (MSH-scale). Patient satisfaction was measured by the CSQ-8 questionnaire.
      Treatment adherence was evaluated by patient and provider self-report. Depression
      severity and remission outcomes were assessed with the Brief PHQ-D. RESULTS:
      Physician facilitation of patient participation improved significantly and to a
      greater extent in the intervention compared to the control group. There was no
      intervention effect for depression severity reduction. Doctor facilitation of
      patient participation, patient-rated involvement, and physician assessment of
      adherence improved only in the intervention group. Patient satisfaction at post
      intervention was higher in the intervention group compared to the control group.
      The consultation time did not differ between groups. CONCLUSION: A shared
      decision-making intervention was better than usual care for improving patient
      participation in treatment decision-making, and patient satisfaction without
      increasing consultation time. Additional research is needed to model causal
      linkages in the decision-making process in regard to outcomes. PRACTICE
      IMPLICATIONS: The study results encourage the implementation of patient
      participation in primary care of depression.

PMID- 17509809
TI  - Cigarette smoking cessation services in outpatient substance abuse treatment
      programs in the United States.
AB  - OBJECTIVE: The objective of this study was to estimate the prevalence and
      determinants of cigarette smoking cessation treatment in U.S. outpatient
      substance abuse treatment (OSAT) units. METHODS: Program directors and clinical
      supervisors from a national sample of 550 OSAT units in the United States were
      surveyed in 2004-2005. Supervisors reported the availability of cigarette smoking
      assessment, and individual or group counseling and pharmacotherapy for smoking
      cessation. This analysis examines whether institutional and resource factors
      influence the delivery of these services. RESULTS: Of OSAT programs in the United
      States, 41% offer smoking cessation counseling or pharmacotherapy, 38% offer
      individual/group counseling, and 17% provide quit-smoking medication. In
      multivariate models, hospital affiliation, service breadth, the priority given to
      physical health, the availability of medication to treat addictive problems,
      assessment of cigarette smoking, and a greater perception of the proportion of
      patients who smoke were associated with the delivery of smoking cessation
      services. Program size and medical staffing also influenced the availability of
      quit-smoking medication. CONCLUSIONS: Of U.S. OSAT programs, two in five offer
      behavioral treatment for smoking cessation, but fewer than one in five provide
      access to pharmacotherapy. Substance abuse treatment programs that are medically
      oriented, provide more comprehensive services, and recognize the burden of
      tobacco smoking among their patients are more likely to deliver evidence-based
      smoking cessation services.

PMID- 17509810
TI  - [Radiological characteristics of the lumbar spine in patients with rheumatoid
      arthritis].
AB  - AIM: The aim of this study was to assess the prevalence and severity of lumbar
      lesions on radiography of patients with rheumatoid arthritis (RA) and of
      population controls and to study the correlation between lumbar lesions and RA
      severity. METHODS: RA patients who met the revised American College of
      Rheumatology criteria were matched with population controls for age, sex, and the
      presence (or absence) of low back pain. Thoracolumbar radiographs were read by
      two observers looking for vertebral fractures, disc space narrowing, endplate
      erosion, facet joint involvement, and osteophytosis. A severity score was
      assigned to each lesion. RESULTS: This study included 60 RA patients and 60
      controls, matched for sex (54 women and 6 men in each group) and age (mean age
      was 47.8+/-14 years in the RA group and 48.4+/-14 years in the control group).
      Prevalence of lumbar lesions was 83% in RA patients and 85% in the control
      subjects (p=0.8). Vertebral fractures were significantly more frequent in RA
      patients (p=0.042). In the RA group, disc space narrowing and the severity of
      endplate erosion were both correlated with higher Larsen grades (p=0.02 and 0.007
      respectively), and the severity of endplate erosion was correlated with coxitis
      (p=0.03). DISCUSSION: In our study, radiological lumbar lesions, except for
      vertebral fractures, were no more common among RA patients than among population
      controls. Endplate erosion and vertebral disc destruction were correlated with RA
      severity scores.

PMID- 17509811
TI  - [Malignant transformation of monoclonal gammopathy of undetermined significance].
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is found in
      approximately 3% of the general population aged 50 years or older. MGUS is a
      premalignant state. The risk of malignant transformation is about 1% per year.
      Some factors predictive of malignant transformation have been identified: type of
      serum monoclonal protein, monoclonal protein value, bone marrow plasmocytosis and
      serum free light chain ratio. Predictive scores combining these factors have
      recently been proposed and make it possible to identify groups of patients with
      significantly different rates of transformation. These scores require validation.
      These scores will probably allow individualization of management and monitoring.

PMID- 17509812
TI  - Symptom prevalence in patients with incurable cancer: a systematic review.
AB  - The suffering of patients with incurable cancer is determined to a large degree
      by the presence and intensity of the symptoms of their disease. Knowledge of
      symptom prevalence is important for clinical practice. The main aim of this study
      was to obtain a reliable estimation of symptom prevalence in patients with
      incurable cancer by performing a systematic review of studies assessing this
      topic. We included 44 studies (including 25,074 patients) on overall symptom
      prevalence (Group 1) and six studies (including 2,219 patients) on symptom
      prevalence during the last one to two weeks of life (Group 2). In these studies,
      symptom prevalence was assessed by a questionnaire, a standardized interview, or
      the medical record. We identified 37 symptoms assessed in at least five studies.
      Almost all symptoms occurred in more than 10% of the patients. Five symptoms
      (fatigue, pain, lack of energy, weakness, and appetite loss) occurred in more
      than 50% of the patients of Group 1. Weight loss occurred significantly more
      often in Group 2 compared to Group 1, and pain, nausea, and urinary symptoms
      occurred significantly less often. Generally, symptom prevalence was highest if
      assessed by a questionnaire. The results of this study should be used to guide
      doctors and nurses in symptom management. Proper attention to symptom burden and
      suffering should be the basis for individually tailored treatment aimed at
      improving or maintaining quality of life of patients in their last period of
      life.

PMID- 17509813
TI  - Hospice care for patients with dementia.
AB  - Dementia is a leading cause of death in the USA. Although guidelines exist to
      determine hospice eligibility for dementia, only a small percentage of patients
      dying with this condition receive hospice care. Hospice recipients with dementia
      have not been well characterized, and little is known about the quality of care
      they receive. The Family Evaluation of Hospice Care (FEHC) survey was adopted by
      the National Hospice and Palliative Care Organization (NHPCO) in 2003 as a
      standard benchmarking tool. The FEHC collects data from bereaved families
      regarding the quality of hospice care. An online repository of 2005 FEHC data was
      used to describe hospice recipients over 65 years of age who died with dementia
      and to examine their families' evaluation of hospice care. Decedents with cancer
      and chronic terminal conditions were also analyzed for comparison purposes. A
      total of 77,123 surveys submitted by 796 hospices nationwide met the study's
      eligibility criteria. Decedent diagnoses were as follows: dementia, n=8,686
      (11.3%); cancer, n=35,693 (46.3%); and other chronic diseases, n=32,744 (42.4%).
      Decedents with dementia were more likely to be >85 years, female, and have length
      of stays >180 days. Evaluation of care in all FEHC domains did not significantly
      differ between groups. Approximately three-quarters of bereaved family members of
      decedents in all groups perceived the overall quality of care as excellent;
      however, opportunities to improve care were also identified. These data suggest
      that the evaluation of hospice care for older patients is generally high, and
      does not vary with respect to terminal diagnoses.

PMID- 17509814
TI  - Mobilization-Observation-Behavior-Intensity-Dementia Pain Scale (MOBID):
      development and validation of a nurse-administered pain assessment tool for use
      in dementia.
AB  - Pain assessment in older persons with severe cognitive impairment (SCI) is a
      challenge due to reduced self-report capacity and lack of movement-related pain
      assessment instruments. The purpose of this article was to describe the
      development of the Mobilization-Observation-Behaviour-Intensity-Dementia Pain
      Scale (MOBID) and to investigate aspects of reliability and validity. MOBID is a
      nurse-administered instrument developed for use in patients with SCI, where
      presence of pain behavior indicators (pain noises, facial expression, and
      defense) may be observed during standardized active, guided movements, and then
      inferred to represent pain intensity. Initially, the MOBID contained seven items
      (observing at rest, mobilization of the hands, arms, legs, turn over in bed,
      sitting on bedside, and teeth/mouth care). This was tested in 26 nursing home
      patients with SCI. Their primary caregivers, five registered nurses and six
      licensed practical nurses (LPNs), rated the patients' pain intensity during
      regular morning care, and by MOBID, both at bedside and from video uptakes. Three
      external raters (LPNs), not knowing the patients, also completed the MOBID by
      rating the videos. Internal consistency of the MOBID indicated high Cronbach's
      alpha (alpha=0.90) after deleting the items for observation at rest and
      observation of teeth/mouth care. MOBID disclosed significantly more pain than did
      pain scorings during regular morning care, and video observation demonstrated
      higher pain intensity than bedside scoring. Intertester reliability for inferred
      pain intensity was high to excellent (intraclass correlation coefficient=0.70
      0.96), but varied between poor and excellent for pain behavior indicators
      (kappa=0.05-0.84). These results suggest that registration of pain behavior
      indicators during active, guided movements, as performed by the MOBID procedure,
      is useful to disclose reliable and valid pain intensity scores in patients with
      SCI.

PMID- 17509815
TI  - Benchmarking the use of opioids in the last days of life.

PMID- 17509816
TI  - Validation and psychometric assessment of a short clinical scale to measure
      chemotherapy-induced nausea and vomiting: the MASCC antiemesis tool.
AB  - There is a lack of clinical tools to facilitate communication between clinicians
      and patients about chemotherapy-induced nausea and vomiting (CINV). The
      Multinational Association of Supportive Care in Cancer (MASCC) has developed such
      a tool, which is an eight-item scale for the assessment of acute and delayed
      nausea and vomiting, and is completed once per cycle of chemotherapy. The aim of
      the current study was to assess its psychometric properties, specifically
      reliability and validity, cultural transferability and equivalence, and
      congruence with proxy assessments, as well as to determine if accuracy of recall
      of CINV events using the MASCC Antiemesis Tool (MAT) differed over time from
      chemotherapy. A prospective study was carried out with adult cancer patients and
      their informal carers from two hospitals, one each in the United Kingdom (UK) and
      United States of America (U.S.). Patients completed the Rhodes Index for nausea,
      vomiting and retching (INVR) daily for the first five days after chemotherapy and
      were then asked to complete the MAT at one week, two weeks, or three weeks after
      chemotherapy. Carers completed an adapted MAT concurrently with patients. The
      sample consisted of 87 patients and 22 informal carers. The internal consistency
      reliability of the scale was high, with Cronbach alphas of 0.77 (patient sample)
      and 0.82 (carer sample). Responses were similar between the UK and U.S. samples
      in terms of nausea and vomiting, and both samples found the scale easy to use.
      Contrasted-groups validity (using age as a grouping variable) and concurrent
      validity (MAT compared with INVR) suggested that the scale is sensitive to detect
      the different dimensions of CINV and performed well against a daily assessment of
      nausea/vomiting (total score correlation r=0.86, P<0.001). Recall of events was
      high even three weeks after chemotherapy (correlations with INVR of 0.44-0.99,
      all P<0.01). Factor analysis clearly identified three factors, namely vomiting,
      acute nausea, and delayed nausea. Proxy assessments by carers were congruent with
      the patients' responses, especially in relation to vomiting. The MAT is a
      reliable, valid, clear, and easy-to-use clinical tool that could facilitate
      discussion between clinicians and patients about their nausea and vomiting
      experience, thereby potentially aiding treatment decisions. Regular assessment of
      nausea and vomiting after chemotherapy has the potential to significantly improve
      CINV management.

PMID- 17509817
TI  - Protective effects of Ginkgo biloba extract on paraquat-induced apoptosis of PC12
      cells.
AB  - Previous studies have suggested that Ginkgo biloba extract (EGb761) has a
      protective potentiality against apoptosis of neurons or neuron-like cells induced
      by MPTP. In this study, the effects of EGb761 on PC12 cells injured by paraquat
      (PQ), a neurotoxin, were tested. The results showed that after incubation of PC12
      cells with EGb761 prior to PQ exposure, the PQ-induced decrease of cell viability
      was significantly reversed, the collapse of mitochondrial membrane potential
      (MMP) was attenuated and the percentage of apoptotic cells was reduced. Moreover,
      EGb761 pretreatment evidently increased the numbers of tyrosine hydroxylase (TH)
      positive and bcl-2 positive cells and degraded the number of caspase-3 positive
      cells in PQ-injured PC12 cells, in comparison to the treatment with PQ alone.
      This study indicates that EGb761 has a neuroprotective effect on paraquat-induced
      apoptosis of PC12 cells. The mechanism underlying the protective effects of
      EGb761 in PQ-injured PC12 cells might be related to the increase of bcl-2
      activation, maintenance of MMP stability and decrease of caspase-3 activation
      through mitochondria-dependent pathway. The results from this study provide an
      experimental basis for the potential use of EGb761 in treatment of Parkinson's
      disease.

PMID- 17509818
TI  - Genomic organization and imprinting of the Peg3 domain in bovine.
AB  - Using multiple mammalian genomic sequences, we have analyzed the evolution and
      imprinting of several genes located in the Peg3 domain, including Mim1 (approved
      name, Mimt1), Usp29, Zim3, and Zfp264. A series of comparative analyses shows
      that the overall genomic structure of this 500-kb imprinted domain has been well
      maintained throughout mammalian evolution but that several lineage-specific
      changes have also occurred in each species. In the bovine domain, Usp29 has lost
      its protein-coding capability, Zim3 has been duplicated, and the expression of
      Zfp264 has become biallelic in brain and testis, which differs from paternal
      expression of mouse Zfp264 in brain. In contrast, the two transcript genes of
      cow, Mim1 and Usp29, both lacking protein-coding capability, are still expressed
      mainly from the paternal allele, indicating the imprinting of these two genes in
      cow. The imprinting of Mim1 and Usp29 along with Peg3 is the most evolutionarily
      selected feature in this imprinted domain, suggesting significant function of
      these three genes, either as protein-coding or as untranslated transcript genes.

PMID- 17509819
TI  - Identification of three novel proteins (SGSM1, 2, 3) which modulate small G
      protein (RAP and RAB)-mediated signaling pathway.
AB  - We report a novel protein family consisting of three members, each of which
      contains RUN and TBC motifs and appears to be associated with small G protein
      mediated signal transduction pathway. We named these proteins as small G protein
      signaling modulators (SGSM1/2/3). Northern blot analysis revealed that human
      SGSM2/3 are expressed ubiquitously in various tissues, whereas SGSM1 is expressed
      mainly in brain, heart, and testis. Mouse possessed the same protein family
      genes, and the in situ hybridization and immunohistochemical staining of tissue
      sections revealed that mouse Sgsm1/2/3 are expressed in the neurons of central
      nervous system, indicating the strong association of Sgsm family with neuronal
      function. Furthermore, endogenous Sgsm1 protein was localized in the trans-Golgi
      network of mouse Neuro2a cells by immunofluorescence microscopy. Expression of
      various cDNA constructs followed by immunoprecipitation assay revealed that human
      SGSM1/2/3 proteins are coprecipitated with RAP and RAB subfamily members of the
      small G protein superfamily. Based on these results, we postulated that the SGSM
      family members function as modulators of the small G protein RAP and RAB-mediated
      neuronal signal transduction and vesicular transportation pathways.

PMID- 17509820
TI  - Vocal fold dimensions in professional opera singers as measured by means of laser
      triangulation.
AB  - A new laser triangulation technique was used to measure vocal fold length and
      width in 27 professional opera singers. The singers belonged to different voice
      register categories: soprano, mezzo, tenor, and bass/baritone. High-speed
      recordings were made during glissandos from each singer's speaking fundamental
      frequency (SFF) up to the highest frequency for which it was possible to place
      the laser spot on the vocal folds. Vocal fold length and width were measured at
      the singers' SFF and then at two or three times the SFF, and for some singers at
      four times the SFF. In addition, measurements were also made at C4 (260 Hz) for
      all singers. The results confirmed that the bass/baritone group had significantly
      longer vocal folds than the soprano group; also, males have significantly longer
      vocal folds than females. Measured values for vocal fold width were significantly
      larger for the bass/baritone group compared with all other groups. A measured
      strain parameter showed different patterns of vocal fold elasticity with
      increasing pitch. The results suggest that although vocal fold length and width
      contribute to a singer's voice register category, there seem to be also other
      parameters that are essential for this distinction.

PMID- 17509821
TI  - Did I really see that? The complex relationship between the visual stimulus and
      visual perception.
AB  - Laryngeal imaging uses optical and electronic means to visualize the larynx.
      Understanding some of the issues related to how the human visual system operates
      and how imaging systems interact with the visual system can help clarify some of
      the artifacts that arise from these technologies. This article describes how the
      visual system can construct coherent perceptions from limited information, how it
      adjusts to current situations, and how the perception of any one part of the
      image depends upon the light levels around each point. In particular, the limited
      field of view and stroboscopic nature of the images can lead to many distortions
      from laryngeal imaging. This article also describes the way that imaging systems
      sample the image, and the lack of stability inherent in an imaging system. The
      article concludes with some observations and recommendations to improve the
      ability to use imaging systems in the diagnosis of laryngeal pathology.

PMID- 17509822
TI  - Peak-to-peak glottal flow amplitude as a function of F(0).
AB  - This study investigated the peak-to-peak (p-t-p) amplitude of the voice source as
      a function of fundamental frequency (F(0)). Nine males and nine females with or
      without singing training produced (1) a glissando from lowest to highest F(0) and
      back in their speaking range on /a:/ and (2) an ascending-descending scale
      pattern on /pa:pa:/. Audio and airflow signals were recorded, the latter picked
      up from a pneumotach mask. F(0) was measured from the audio signal and the oral
      pressure during the /p/ occlusion for an estimate of subglottal pressure. Airflow
      signal was inverse filtered and the p-t-p amplitude was measured for 10 F(0)
      values, equidistantly spaced along the subject's F(0) range in semitones, thus
      facilitating comparison between individuals and genders. Most females and males
      showed both a wide range of relatively large p-t-p amplitude in the speech range
      and a more or less pronounced p-t-p amplitude maximum, which was located on
      average at 232 and 162 Hz, respectively. The p-t-p amplitude maximum seems to
      reflect a complicated interplay between factors that tend to increase and those
      that tend to decrease the p-t-p amplitude with increasing F(0).

PMID- 17509823
TI  - Normal voice in children between 6 and 12 years of age: database and nonlinear
      analysis.
AB  - This study was carried out using a transversal design. It aimed to investigate
      possible changes of the normal voice in children before mutation, to create a
      database for the parameters used in the study, and to examine the use of fractal
      dimension and the largest Lyapunov exponent (LLE) in the assessment of
      nonpathological phenomena. Two hundred twelve children were enrolled: 111 females
      and 101 males; and 9 six-year-olds, 24 seven-year-olds, 18 eight-year-olds, 25
      nine-year-olds, 27 ten-year-olds, 55 eleven-year-olds, and 54 twelve-year-olds.
      Fundamental frequency (Fo) decreased with age and was lower in boys than in
      girls. Jitter and shimmer did not significantly differ with age or gender.
      Fractal dimension and LLE were significantly lower in boys; LLE decreased with
      age. The present series confirmed the established findings that Fo is lower in
      boys than in girls, even before mutation, and decreases with age; two other
      classical voice analysis parameters, jitter and shimmer, also showed the same
      behavior as described in the literature. The study of nonlinear parameters
      (fractal dimension and LLE) showed that laryngeal dynamics is more stable in boys
      than in girls, and that stability is correlated with age.

PMID- 17509824
TI  - The innervation of the posterior cricoarytenoid muscle: exploring clinical
      possibilities.
AB  - Manipulation of the nerve supply to the posterior cricoarytenoid (PCA) muscle has
      potential for ameliorating the symptoms of some neurologic conditions such as
      abductor spasmodic dysphonia. The anatomy of the nerve supply to the PCA is
      better understood than in previous eras, but the anatomical understanding has not
      translated to clinical application yet. Microscopic dissection allowed the
      identification and measurement of the branches from the recurrent laryngeal
      nerves (RLNs) to the PCA in 43 human cadaver larynges. The cricothyroid (CT)
      joint was the primary landmark for measurement. Other structural measurements
      were also made on the larynges. All of the PCA muscles received innervation from
      the anterior division of the RLN. The number of direct branches from the RLN
      ranged from 1 to 5 (average 2.3) More than 70% of PCA muscles also received 1-3
      branches off of the branch to the interarytenoid (IA) muscle. Less than half of
      PCA muscles received any kind of nerve branches from the posterior division of
      the RLN. Branches to the PCA most commonly departed the main RLN in its vertical
      segment and all entered the muscle from its deep surface. All branches departed
      the RLN within an average of 9.5mm from the CT joint; the branch to the IA occurs
      distal to this point. The innervation to the PCA is complex and redundant, and
      the segment of the RLN supplying those branches is difficult to expose safely.
      For these reasons, selective denervation or reinnervation procedures limited to
      the nerve branches may be technically difficult. When needing only to denervate
      the PCA, this can be accomplished by removing a portion of the PCA and the
      underlying nerve supply. Surgical technique should be based upon the
      understanding of the anatomy of the PCA muscle and its nerve supply.

PMID- 17509825
TI  - Laryngeal muscle activity in giggle: a damped oscillation model.
AB  - The acoustic properties of giggle, a mild form of laughter, were studied. The
      purpose was to determine if there is some uniqueness to the frequency and number
      of vocalization bursts in giggle. The underlying hypothesis was that a
      neuromechanical oscillator serves as an activator for rhythmic vocalizations, as
      in vibrato, with a pair of agonist-antagonist adductor muscles alternating in a
      180 degrees phase relationship. Electromyographic activity of the posterior
      cricoarytenoid muscle was always measured, in conjunction with either lateral
      cricoarytenoid or thyroarytenoid muscle activity. Results indicate that muscle
      activations do alternate and that these activations do not diminish during
      successive bursts, even though the amplitude and duty ratio of the bursts
      decreases. It is reasoned that reduced lung pressure and lung volume limit the
      number of bursts and their duty ratio, while speed of intrinsic laryngeal muscle
      contraction dictates the burst frequency.

PMID- 17509826
TI  - Laryngeal mechanisms during human 4-kHz vocalization studied with CT,
      videostroboscopy, and color Doppler imaging.
AB  - The objective of this study was to investigate the underlying laryngeal
      mechanisms during the specific human 4-kHz vocalization. The laryngeal
      configuration during this vocalization was measured using high-resolution
      computerized tomographic scan and videostrobolaryngoscopy. The color Doppler
      imaging (CDI) of medical ultrasound was used to detect the vibrations of glottal
      and supraglottal mucosa. During the 4-kHz vocalization, the ventricular folds
      were adducted in the shape of a bimodal chink and the vocal folds were shaped as
      a "V" with an opening at the posterior glottis. In the coronal view, the
      laryngeal ventricles had collapsed and a divergent shaped conduit was observed at
      the posterior portion of the larynx. The surface mucosa vibration detected by CDI
      was noted over the bilateral ventricular folds and aryepiglottic folds. The
      vibration displacement was estimated to be on the order of 0.1mm. This vibration
      amplitude was too small to be detected in videostrobolaryngoscopy. The laryngeal
      configuration and CDI data suggested a diffuser jet with periodic vorticity
      bursts in the larynx producing 4 kHz voice.

PMID- 17509827
TI  - Pitch discrimination and pitch matching abilities with vocal and nonvocal
      stimuli.
AB  - Various stimulus types have been investigated in pitch discrimination and pitch
      matching tasks. However, previous studies have not explored the use of recorded
      samples of an individual's own voice in performing these two tasks. The purpose
      of this study was to investigate pitch discrimination and pitch matching
      abilities using three stimuli conditions (participant's own voice, a neutral
      female voice, and nonvocal complex tones) to determine if pitch discrimination
      and/or pitch matching abilities are influenced by the type of stimuli presented.
      Results of the pitch discrimination tasks yielded no significant difference in
      discrimination ability for the three stimuli. For the pitch matching tasks, a
      significant difference was found for the participants' voice versus neutral
      female voice and the participants' voice versus tonal stimuli. There was no
      significant difference in pitch matching ability between the neutral female voice
      and the tonal stimuli. There was no significant correlation between pitch
      discrimination and pitch matching abilities for any of the three stimuli types.
      These results suggest that it is easier to match the pitch of one's own voice
      than to match the pitch of a neutral female voice and nonvocal complex tones,
      although no difference was found for pitch discrimination abilities. One possible
      implication of this study is that differences in matching the pitch of one's own
      voice compared to matching other stimuli types may help to differentiate the
      source of singing inaccuracy (motor vs discrimination skills).

PMID- 17509828
TI  - Effects of voice therapy: a systematic review.
AB  - Medical as well as paramedical treatments should be evaluated by scientific
      methods. This systematic review focuses on the effects of voice therapy,
      excluding pharmacological or surgical treatments. In general, statistically
      significant positive but modest and varying therapy effects are found. Many of
      these effect studies cope with diverse methodological problems. Furthermore, the
      conclusions of most studies cannot be generalized easily or compared to one
      another. As a consequence, many issues in the field of effects of voice therapy
      have yet been unanswered.

PMID- 17509829
TI  - Vibratory regime classification of infant phonation.
AB  - Infant phonation is highly variable in many respects, including the basic
      vibratory patterns by which the vocal tissues create acoustic signals. Previous
      studies have identified the regular occurrence of nonmodal phonation types in
      normal infant phonation. The glottis is like many oscillating systems that,
      because of nonlinear relationships among the elements, may vibrate in ways
      representing the deterministic patterns classified theoretically within the
      mathematical framework of nonlinear dynamics. The infant's preverbal vocal
      explorations present such a variety of phonations that it may be possible to find
      effectively all the classes of vibration predicted by nonlinear dynamic theory.
      The current report defines acoustic criteria for an important subset of such
      vibratory regimes, and demonstrates that analysts can be trained to reliably use
      these criteria for a classification that includes all instances of infant
      phonation in the recorded corpora. The method is thus internally comprehensive in
      the sense that all phonations are classified, but it is not exhaustive in the
      sense that all vocal qualities are thereby represented. Using the methods thus
      developed, this study also demonstrates that the distributions of these phonation
      types vary significantly across sessions of recording in the first year of life,
      suggesting developmental changes. The method of regime classification is thus
      capable of tracking changes that may be indicative of maturation of the
      mechanism, the learning of categories of phonatory control, and the possibly
      varying use of vocalizations across social contexts.

PMID- 17509830
TI  - Oculodentodigital dysplasia with mandibular retrognathism and absence of
      syndactyly: a case report with a novel mutation in the connexin 43 gene.
AB  - Oculodentodigital dysplasia (ODDD) is a rare, autosomal dominant pleiotropic
      disorder, caused by mutations in the Connexin 43 (Cx43 or GJA1) gene. Described
      here is the case of a 10-year-old girl with enamel hypoplasia, typical facies and
      mental delay, initially thought to be related to an unknown metabolic disorder.
      Careful clinical re-evaluation revealed a type of ODDD, characterised by the
      predominance of facial and ophthalmological involvement with mandibular
      retrognathism, and by the absence of cutaneous hand or foot syndactyly. A novel
      single-sequence variation (Nt460A>G) in exon 2, resulting in the substitution of
      alanine for threonine at amino acid 154, was found. These findings confirm once
      again the highly variable phenotypic expression caused by Cx43 mutations.

PMID- 17509831
TI  - Aggressive maxillary squamous odontogenic tumour in a child: histological dilemma
      and adaptative surgical behaviour.
AB  - A case of a maxillary osteolytic tumour is described in a 9-year-old boy.
      Histological analysis led to an initial diagnosis of benign squamous odontogenic
      tumour, although this was not straightforward due to swelling, and cellular
      pseudo-malignant and non-specific signs. Because of the young age of the patient,
      a local surgical tumourectomy was first chosen with respect to the mixed
      dentition. For 10 months, the evolution was satisfactory. Then, a very aggressive
      tumoural recurrence with lip and palate infiltration led to doubts as to the
      histologic nature of the tumour. Efficient collaboration between several
      specialized pathologist teams finally confirmed that this was a squamous
      odontogenic tumour but in a very aggressive form. Radical surgery was then
      carried out.

PMID- 17509832
TI  - Minimizing risk to the vascularity of the osteotomized fibula: a technical note.

PMID- 17509833
TI  - fMRI correlates of interictal epileptic activity in patients with idiopathic
      benign focal epilepsy of childhood. A simultaneous EEG-functional MRI study.
AB  - EEG-correlated fMRI (EEG/fMRI) can identify alterations of brain function
      associated with interictal epileptiform discharges (IED). fMRI activation can
      localize the irritative zone and indicate functional disturbance distant from the
      spike focus. This might be of particular interest in paediatric epilepsy
      syndromes with frequent IED. Using simultaneous EEG/fMRI in a 3T MR scanner we
      studied blood oxygen level-dependent (BOLD) signal changes related to spontaneous
      IED in 10 children with typical and atypical benign focal epilepsy of childhood
      (BFE) or benign epileptic activity of childhood (BEAC). EEG artefacts were
      subtracted offline and IED were used as regressors for event-related fMRI
      analysis in SPM2. In four of the seven children with IED during EEG/fMRI we found
      IED related positive and negative signal changes (p<0.001, uncorrected). In three
      children we found only significant negative signal changes. At a more liberal
      threshold (p<0.05, uncorrected) these three children had positive signal changes
      congruent with the four children with significant positive signal changes. In
      summary, we found positive or negative signal changes in perisylvian, central,
      premotor and prefrontal regions. One child showed additional bilateral occipital
      fMRI activation. In addition to former reports our results indicated that frontal
      brain areas are functionally disturbed during IED corresponding to general
      neuropsychological findings in BFE and BEAC. We conclude that using EEG/fMRI it
      might be possible to localize generators of IED and functionally disturbed brain
      regions in children with BFE. Further studies are required to differentiate
      between BFE subtypes and to identify fMRI signatures of specific syndromes or
      corresponding neuropsychological deficits.

PMID- 17509834
TI  - Clinical correlates of later violence and criminal offences in schizophrenia.
AB  - BACKGROUND: Violence and criminality in patients with schizophrenia has been
      described in several studies but prediction of later criminal behavior is
      difficult. METHODS: We reviewed the national crime register for records of
      criminal offences committed by 1662 patients with schizophrenia treated between
      1990 and 1995 in the Psychiatric Hospital of the University of Munich. Analyses
      were performed to determine predictors of later criminal behavior, and the
      psychopathological syndrome scales in the Association for Methodology and
      Documentation in Psychiatry (AMDP) system were used to establish possible
      psychopathological characteristics for such behavior. RESULTS: One hundred and
      sixty nine (10.2%) of the 1662 patients had been convicted in the 7-12 years
      after discharge, whereby male patients (117 of 685, 17.1%) outnumbered female
      patients ( 52 of 977, 5.3%) by more than 3 to 1. The rate of violent crimes was
      especially high: 62 (3.7%) patients were convicted for physical injury offences.
      Five cases of manslaughter or murder were recorded. AMDP syndrome scales were
      found to be predictive for later criminal offences. Significantly higher rates of
      criminal conviction and recidivism were found for patients with lack of insight
      at discharge. Analyses also showed a significantly higher risk of non-violent and
      violent crimes in patients with a hostility syndrome at admission and discharge.
      There was a significantly lower incidence of criminal behavior in subjects with a
      depressive syndrome. CONCLUSION: Data indicate a significant rate of minor and
      serious physical injury offences in former inpatients with schizophrenia.
      Moreover, results identify risk factors for future non-violent and violent
      criminal behavior in patients with schizophrenia.

PMID- 17509835
TI  - Temperament and character in violent schizophrenic patients.
AB  - Preliminary evidence shows that personality traits are important in determining
      violent behavior in schizophrenia. As only some patients with schizophrenia show
      a greater risk for violence, this risk may therefore be considered as dynamic,
      varying as a function of the extent to which certain personality dimensions are
      present and the degree to which environmental events moderate or exacerbate their
      expression. OBJECTIVE: To compare temperament and character dimensions between
      violent and non-violent schizophrenic patients and to determine which temperament
      and character dimensions are predictors of violent behavior in schizophrenia.
      METHOD: We recruited 102 schizophrenic patients without concomitant substance
      abuse 4 months prior to the assessment. Diagnoses were based on the SCID-I.
      Personality dimensions were assessed with the Temperament and Character Inventory
      and violent behaviors with the Overt Aggression Scale. RESULTS: Higher levels of
      the temperament dimension novelty seeking and a lower cooperativeness, as a
      character dimension, were risk factors for violent behavior in schizophrenic
      patients. DISCUSSION: Our data indicate that schizophrenic patients will show a
      greater risk for violence according to certain personality configurations and the
      degree to which environmental events moderate or exacerbate their expression.

PMID- 17509836
TI  - Evidence of a latitudinal gradient in the age at onset of schizophrenia.
AB  - Variation in the age at onset of a multifactorial disease often reflects
      variation in cause. Here we show a linear latitudinal gradient in the mean age at
      onset of schizophrenia in 13 northern hemisphere cities, ranging from 25 years
      old in Cali, Columbia (at 4 degrees north) to 35 years old in Moscow, Russia (at
      56 degrees north). To our knowledge, this striking association has not been
      previously reported. We consider several explanations, including the effects of
      pathogen stress, natural selection, sexual selection, migration, life-history
      profiles, or some combination of these factors, and we propose a test of
      competing causal hypotheses.

PMID- 17509837
TI  - The S4-intermediate pathway for the oxidation of thiosulfate by the
      chemolithoautotroph Tetrathiobacter kashmirensis and inhibition of tetrathionate
      oxidation by sulfite.
AB  - Chemolithotrophic oxidation of reduced sulfur compounds was studied in the
      betaproteobacterium Tetrathiobacter kashmirensis in correlation with its
      transposon (Tn5-mob)-inserted mutants impaired in sulfur oxidation (Sox(-)) and
      found to be carried out via the tetrathionate intermediate (S(4)I) pathway. The
      group of physiologically identical Sox(-) mutant strains presently examined could
      fully oxidize thiosulfate supplied in the media to equivalent amounts of
      tetrathionate but could only convert 5-10% of the latter to equivalent amounts of
      sulfite (equivalences in terms of mug atoms of S ml(-1)). These mutants were
      found to possess intact thiosulfate dehydrogenase, but defunct sulfite
      dehydrogenase, activities. Single copies of Tn5-mob in the genomes of the Sox(-)
      mutants were found inserted within the moeA gene, responsible for molybdopterin
      cofactor biosynthesis. This explained the inactivity of sulfite dehydrogenase.
      Chemolithotrophic oxidation of tetrathionate and sulfite by T. kashmirensis was
      found to be inhibited by 12 mM tungstate, whose effect could however be reversed
      by further addition of 15 mM molybdate. In mixotrophic medium, the mutants showed
      uninterrupted utilization of maltose but inhibition of tetrathionate utilization
      due to accumulation of sulfite. When sulfite was added to wild type cultures
      growing on tetrathionate-containing chemolithoautotrophic medium, it was found to
      render concentration-dependent inhibition of oxidation of tetrathionate. Our
      findings indicate that sulfite molecules negatively regulate their own synthesis
      by plausible inhibitory interaction(s) with enzyme(s) responsible for the
      oxidation of tetrathionate to sulfite; thereby clearly suggesting that one of the
      control mechanisms of chemolithotrophic sulfur oxidation could be at the level of
      sulfite.

PMID- 17509838
TI  - Antimicrobial resistance and evaluation of susceptibility testing among
      pathogenic enterococci isolated from dogs and cats.

PMID- 17509839
TI  - Organization, structure and activity of proteins in monolayers.
AB  - Many different processes take place at the cell membrane interface. Indeed, for
      instance, ligands bind membrane proteins which in turn activate peripheral
      membrane proteins, some of which are enzymes whose action is also located at the
      membrane interface. Native cell membranes are difficult to use to gain
      information on the activity of individual proteins at the membrane interface
      because of the large number of different proteins involved in membranous
      processes. Model membrane systems, such as monolayers at the air-water interface,
      have thus been extensively used during the last 50 years to reconstitute proteins
      and to gain information on their organization, structure and activity in
      membranes. In the present paper, we review the recent work we have performed with
      membrane and peripheral proteins as well as enzymes in monolayers at the air
      water interface. We show that the structure and orientation of gramicidin has
      been determined by combining different methods. Furthermore, we demonstrate that
      the secondary structure of rhodopsin and bacteriorhodopsin is indistinguishable
      from that in native membranes when appropriate conditions are used. We also show
      that the kinetics and extent of monolayer binding of myristoylated recoverin is
      much faster than that of the nonmyristoylated form and that this binding is
      highly favored by the presence polyunsaturated phospholipids. Moreover, we show
      that the use of fragments of RPE65 allow determine which region of this protein
      is most likely involved in membrane binding. Monomolecular films were also used
      to further understand the hydrolysis of organized phospholipids by phospholipases
      A2 and C.

PMID- 17509840
TI  - Long-term multidisciplinary therapy decreases predictors and prevalence of
      metabolic syndrome in obese adolescents.

PMID- 17509841
TI  - A comprehensive review on the stinging nettle effect and efficacy profiles. Part
      II: urticae radix.
AB  - Nettle root is recommended for complaints associated with benign prostatic
      hyperplasia (BPH). We therefore conducted a comprehensive review of the
      literature to summarise the pharmacological and clinical effects of this plant
      material. Only a few components of the active principle have been identified and
      the mechanism of action is still unclear. It seems likely that sex hormone
      binding globulin (SHBG), aromatase, epidermal growth factor and prostate steroid
      membrane receptors are involved in the anti-prostatic effect, but less likely
      that 5alpha-reductase or androgen receptors are involved. Extract and a
      polysaccharide fraction were shown to exert anti-inflammatory activity. A
      proprietary methanolic nettle root extract and particular fractions inhibited
      cell proliferation. Isolated lectins (UDA) were shown to be promising
      immunomodulatory agents, having also anti-viral and fungistatic effects. However,
      despite these in vitro studies it is unclear whether the in-vitro or animal data
      are a surrogate for clinical effects. The clinical evidence of effectiveness for
      nettle root in the treatment of BPH is based on many open studies. A small number
      of randomised controlled studies indicate that a proprietary methanolic extract
      is effective in improving BPH complaints. However, the significance and magnitude
      of the effect remains to be established in further confirmatory studies before
      nettle root treatment may be accepted in the guidelines for BPH treatment. The
      risk for adverse events during nettle root treatment is very low, as is its
      toxicity. Pre-clinical safety data remain to be completed.

PMID- 17509842
TI  - ITS sequence analysis used for molecular identification of the Bupleurum species
      from northwestern China.
AB  - Radix Bupleuri (Chaihu), a famous Traditional Chinese Medicine, is derived from
      the dried roots of Bupleurum chinense DC. and B. scorzonerifolium Willd. But
      nowadays, other nine species and varieties from genus Bupleurum are also used as
      Radix Bupleuri in northwestern China. The authentic identification of dried roots
      of B. chinense and B. scorzonerifolium, however, is difficult to just base on the
      appearance and morphology. A molecular genetic method was developed to help
      discriminate the original species of Radix Bupleuri. The ITS sequences (
      approximately 600 bp) were amplified by the PCR technique from genomic DNA
      isolated from all the collected samples. According to analyzing the information
      given by ITS sequences, the conclusion can be made that ITS sequence could serve
      as markers for authentication of Radix Bupleuri.

PMID- 17509843
TI  - ADAMTS-like 2 (ADAMTSL2) is a secreted glycoprotein that is widely expressed
      during mouse embryogenesis and is regulated during skeletal myogenesis.
AB  - ADAMTS-like 2 (ADAMTSL2), is a secreted protein resembling the ancillary domains
      of the ADAMTS proteases, but with distinct structural features. It has 7
      thrombospondin type-1 repeats (TSRs), but an unusually long spacer module, which
      in both humans and mice, contains a novel insertion bearing six N-glycosylation
      sites. The ADAMTSL2 protein expressed in HEK293F and COS-1 cells, is a cell
      surface and extracellular matrix binding glycoprotein, with N-linked carbohydrate
      constituting approximately 20% by mass. The 4.0 kb Adamtsl2 mRNA is found most
      abundantly in adult mouse liver, lung and spleen by northern blotting. During
      mouse embryogenesis, Adamtsl2 was expressed most strongly in the third week of
      gestation. Adamtsl2 mRNA was detected by in situ hybridization in developing
      skeletal muscle, liver, bronchial and arterial smooth muscle, skin,
      intervertebral disc, perichondrium, pancreas and spinal cord. Immunohistochemical
      localization of ADAMTSL2 protein was similar to mRNA expression. Detection of
      Adamtsl2 mRNA and protein in developing skeletal myotubes, but not
      undifferentiated myogenic precursors led us to investigate its regulation during
      in vitro myogenic differentiation. In C2C12 and 23A2 myogenic cells, but not in
      23A2 cells rendered non-myogenic by expression of G12V:H-Ras (9A2 cells),
      differentiation induced by serum starvation triggered expression of Adamtsl2
      mRNA, coordinately with Myog, a marker of muscle differentiation. Furthermore,
      activation of the key myogenic determinant MyoD in 10T1/2 fibroblasts also
      triggered expression of Adamtsl2 mRNA. Collectively, the data suggest that
      induction of Adamtsl2 mRNA is an integral feature of myogenesis.

PMID- 17509844
TI  - Molecular characterization of strawberry pathogen Gnomonia fragariae and its
      genetic relatedness to other Gnomonia species and members of Diaporthales.
AB  - Gnomonia fragariae is a poorly studied ascomycete belonging to Diaporthales.
      Originally G. fragariae was considered a saprophyte occurring on dead tissues of
      strawberry plants. Recently this fungus was found in Latvia and Sweden, and it
      was proven to be the cause of severe root rot and petiole blight of strawberry.
      Thirteen isolates of this pathogen and several other Gnomonia species occurring
      on rosaceous hosts were characterized by molecular analysis using nucleotide
      sequences of partial LSU rRNA gene and the total ITS region. The homologous
      regions from relevant diaporthalean taxa available in the GenBank were also
      included and compared with the taxa sequenced in this study. Phylogenetic
      analyses revealed that G. fragariae, G. rubi, and Gnomonia sp. (CBS 850.79) were
      genetically different from G. gnomon, the type species of the genus, and other
      members of Gnomoniaceae. The analyses showed that G. fragariae and Hapalocystis
      were genetically very closely related, forming a phylogenetic clade, which is
      possibly presenting a new family in the Diaporthales. Morphological comparisons
      of the Gnomonia species on the basis of commonly used criteria for the taxonomy
      of Diaporthales, so far did not reveal any evident features for the polyphyletic
      status of Gnomonia.

PMID- 17509845
TI  - Intra-isolate heterogeneity of the ITS region of rDNA in Pythium helicoides.
AB  - Heterogeneity of the rDNA ITS region in Pythium helicoides and the phylogenetic
      relationship between P. helicoides and closely related species were investigated.
      In PCR-RFLP analysis of the rDNA ITS region of six P. helicoides isolates
      investigated, including the type culture, intraspecific variation was found at
      the HhaI site. The total length of fragments was longer than before cutting,
      indicating sequence heterogeneity within isolates. Digestion of the cloned rDNA
      ITS region derived from seven isolates with HhaI revealed polymorphisms among and
      within single zoospore isolates, and variability of the region was also present
      among the clones derived from the same isolate. To test whether the rDNA ITS
      region of closely related species and other regions in the genome of P.
      helicoides are also variable, the rDNA ITS region of P. ultimum and the
      cytochrome oxydase II (cox II) gene encoded in mitochondria were sequenced. P.
      ultimum had little variation in the rDNA ITS region. The cox II gene sequences of
      both species revealed only a low intraspecific variability and no intra-isolate
      variation. In the phylogenic tree based on the rDNA ITS sequences, all clones of
      P. helicoides formed one large clade that was distinct from the clades comprising
      morphologically similar species, such as P. oedochilum and P. ostracodes, and was
      closely related to P. chamaehyphon rather than the other species.

PMID- 17509846
TI  - Diversity of viruses in Cryphonectria parasitica and C. nitschkei in Japan and
      China, and partial characterization of a new chrysovirus species.
AB  - We surveyed native populations of the chestnut blight fungus, Cryphonectria
      parasitica, in Japan and China, and C. nitschkei, a sympatric species on chestnut
      trees in Japan, to learn more about the diversity of hypoviruses and other double
      stranded (ds) RNA viruses. In a sample of 472 isolates of C. parasitica and 45
      isolates of C. nitschkei from six prefectures in Japan, we found 27 containing
      one or more dsRNAs. Twelve isolates of C. parasitica and two isolates of C.
      nitschkei were infected with Cryphonectria hypovirus 1 (CHV-1); four of these 12
      C. parasitica isolates also contained other dsRNAs that did not hybridize to CHV
      1. In China, only one of 85 C. parasitica isolates was CHV-1-infected; no dsRNAs
      were detected in the other isolates from China. No other known hypoviruses were
      found in this study. However, we found two previously undescribed dsRNAs in Japan
      approximately 9kb in size that did not hybridize to each other or to any known
      dsRNAs from C. parasitica. We also found three additional groups of dsRNAs, one
      of which represents the genome of a new member of the virus family Chrysoviridae
      and was found only in C. nitschkei; the other two dsRNAs were found previously in
      isolates of C. parasitica from Japan or China. The most significant result of
      this survey is the discovery of novel dsRNAs that can be characterized in future
      research.

PMID- 17509847
TI  - The enigmatic Squamanita odorata (Agaricales, Basidiomycota) is parasitic on
      Hebeloma mesophaeum.
AB  - Squamanita odorata is an agaric which is parasitic on unrecognizable, previously
      unidentifiable sporophores of a fungal host that is transformed into galls at the
      bases of the parasite's sporophore. Amplification and sequencing portions of the
      nuclear (ITS) and mt rDNA from three samplings originating from two sites (from
      France and from Switzerland) demonstrate that the galls produce sequences that
      are identical to that of co-occurring Hebeloma mesophaeum. This demonstrates that
      S. odorata is a biotrophic parasite on Hebeloma mesophaeum.

PMID- 17509848
TI  - Identification of two group A chitinase genes in Botrytis cinerea which are
      differentially induced by exogenous chitin.
AB  - Chitin-degrading enzymes represent potential targets for pesticides in the
      control of plant pathogenic fungi. Here we describe the cloning, molecular
      characterization, and expression analysis of two putative chitinases of Botrytis
      cinerea, a pathogenic fungus infecting a wide range of plants. On the basis of
      conserved motifs from family 18 of the glycosyl hydrolases and group A of the
      fungal chitinases, two fragments (BcchiA and BcchiB) were cloned and sequenced.
      Expression of BcchiA and BcchiB chitinase genes upon growth under different
      conditions was analysed using RT-PCR. We observed that BcchiA expression was
      suppressed by glucose, whereas it was strongly stimulated in the presence of
      chitin or chitin degradation products. Conversely, BcchiB expression was not
      suppressed by glucose and was not stimulated by chitin or chitin degradation
      products. The difference in expression regulation is indicative of a functional
      divergence between the two chitinase paralogous genes.

PMID- 17509849
TI  - Re-consideration of Peronospora farinosa infecting Spinacia oleracea as distinct
      species, Peronospora effusa.
AB  - Downy mildew is probably the most widespread and potentially destructive global
      disease of spinach (Spinacia oleracea). The causal agent of downy mildew disease
      on various plants of Chenopodiaceae, including spinach, is regarded as a single
      species, Peronospora farinosa. In the present study, the ITS rDNA sequence and
      morphological data demonstrated that P. farinosa from S. oleracea is distinct
      from downy mildew of other chenopodiaceous hosts. Fifty-eight spinach specimens
      were collected or loaned from 17 countries of Asia, Europe, Oceania, North and
      South America, which all formed a distinct monophyletic group. No
      intercontinental genetic variation of the ITS rDNA within Peronospora accessions
      causing spinach downy mildew disease was found. Phylogenetic trees supported
      recognition of Peronospora from spinach as a separate species. Microscopic
      examination also revealed morphological differences between Peronospora specimens
      from Spinacia and P. farinosa s. lat. specimens from Atriplex, Bassia, Beta, and
      Chenopodium. Consequently, the name Peronospora effusa should be reinstated for
      the downy mildew fungus found on spinach. Here, a specimen of the original
      collections of Peronospora effusa is designated as lectotype.

PMID- 17509850
TI  - Accelerated nrDNA evolution and profound AT bias in the medicinal fungus
      Cordyceps sinensis.
AB  - Cordyceps sinensis is a reputed medicinal fungus growing parasitically on buried
      larvae of ghost moths in Asian high-altitude grassland ecosystems. We have
      analysed the intraspecific ITS nrDNA (ITS1, 5.8S gene, ITS2) variation among 71
      sequences of C. sinensis available in EMBL/Genbank. The ITS sequences, submitted
      to Bayesian ML analyses, were distributed into five groups, referred to as A-E.
      Nine of the sequences (groups D and E) grouped with distantly related
      hypocrealean/clavicipitalean taxa and are interpreted as sequences erroneously
      accessioned under wrong taxon names. The remaining 62 sequences constituted three
      highly supported clades (groups A-C), that may represent cryptic (phylogenetic)
      species currently ascribed to C. sinensis. A remarkably high sequence divergence
      occurred in the 5.8S gene between the three groups. Sequences of groups B and C
      showed accelerated substitution rates and high AT nucleotide bias. We hypothesize
      that the accelerated evolution and AT bias have been caused by a shift in life
      historical attributes or ecology. We also suggest that the recorded differences
      in medicinal effects among C. sinensis populations may be attributed to the
      existence of genetically differentiated chemotypes in this morphotaxon.

PMID- 17509851
TI  - The protective effect of selenium inorganic forms against cadmium and silver
      toxicity in mycelia of Pleurotus ostreatus.
AB  - The effect of two inorganic selenium forms has been investigated in the mycelia
      of Pleurotus ostreatus exposed to cadmium and silver salts in the shaken
      cultures. The degree of toxicity was assessed by the determination of
      malondialdehyde (MDA; a common biomarker of lipid peroxidation). The mycelia were
      exposed to one element form (up to 5 mg l(-1)) and also to the following
      combinations: cadmium(II) + selenium(IV); cadmium(II) + selenium(VI); silver(I) +
      selenium(IV); silver(I) + selenium(VI). The concentrations of cadmium, silver,
      selenium, and MDA were assessed in the mixed cytosol and cell membrane fractions
      (CCM). A positive correlation between MDA and cadmium was found in the CCM
      (beta=0.7775, P=0.0001), whereas the effect of silver was less significant
      (beta=0.4642, P=0.039). These results indicate that silver(I) and cadmium(II)
      have different capacities to induce lipid peroxidation in P. ostreatus. The
      protective role of selenium against metal-induced oxidative damage was found to
      be dependent on the oxidation state of the element form in the growth medium. The
      strongest beneficial effect was observed in mycelia exposed to cadmium(II) +
      selenium(IV) (inverse correlation between MDA and selenium in the CCM: beta=
      0.7129, P=0.009) and it has been ascribed to a lower incorporation of the toxic
      metal and/or to possible intracellular interaction between selenium and cadmium.
      Under exposure to silver(I), the protective effect of selenium(IV) was less
      noticeable (correlation between MDA and selenium in the CCM; beta=-0.6068,
      P=0.036); in the presence of selenium(VI), no beneficial effect was observed.

PMID- 17509852
TI  - Strength and endurance of the respiratory and handgrip muscles after the use of
      flunisolide in normal subjects.
AB  - OBJECTIVE: To evaluate the effects of the inhaled flunisolide upon the strength
      and endurance of the respiratory and peripheral muscles of normal subjects.
      DESIGN: A randomized, double blind and placebo-controlled study. SETTING: A
      university-affiliated teaching hospital. PARTICIPANTS: Thirteen normal volunteers
      selected from a graduation course. INTERVENTION: Subjects were randomly allocated
      to receive a placebo or corticosteroid (flunisolide) to be inhaled twice a day
      for 4 weeks. After 2 weeks of a washout period, subjects who were receiving the
      placebo, received flunisolide and vise versa for another 4-week period.
      MEASUREMENTS AND RESULTS: Spirometry was used to define the volunteers as being
      normal in terms of pulmonary function. During the study, subjects performed tests
      of respiratory muscle function (strength and endurance), measurements of handgrip
      strength and endurance and anthropometric measurements. Muscle strength was
      measured each week while muscle endurance was measured every 2 weeks. There was
      no significant difference in the maximal inspiratory and expiratory pressure and
      handgrip strength during weeks 1-4 when the subjects used either flunisolide or
      placebo. However, we observed an increase in the endurance time of the
      respiratory and handgrip muscles in the 4th week of both flunisolide and placebo
      use, what may be considered due to a learning effect. CONCLUSION: Inhalation of
      flunisolide by normal subjects for 1 month does not cause any acute or clinically
      perceived effect in the peripheral or respiratory muscles.

PMID- 17509853
TI  - Current diagnosis and management of idiopathic pulmonary fibrosis: a survey of
      academic physicians.
AB  - Little is known about practice patterns regarding the diagnosis and management of
      idiopathic pulmonary fibrosis (IPF). This study attempts to define the practice
      patterns of academic pulmonologists caring for patients with IPF. Academic
      pulmonologists in the United States were surveyed electronically. Completed
      surveys were received from 272 respondents (representing approximately 10% of
      academic pulmonologists). The majority agreed that high-resolution computed
      tomography can establish the diagnosis of IPF, and that surgical lung biopsy is
      indicated when the diagnosis remains unclear. Bronchoscopy is little utilized.
      Most respondents treat patients with medications, but there is no consensus
      regarding treatment regimen. These results suggest there is general consensus
      regarding the approach to diagnosis, but that there is no consensus about medical
      management in IPF.

PMID- 17509854
TI  - All-trans retinoic acid regulates c-jun expression via ERK5 in cardiac myoblasts.
AB  - Retinoic acid (RA) is an active metabolite of vitamin A and plays an important
      role in biological processes including cell proliferation. MAPKs play a pivotal
      role in regulating many critical cellular processes in the heart. The aim of the
      study was to determine whether all-trans RA (atRA) affects the proliferation of
      H9c2 rat ventricular cells and whether ERK family is involved in this process.
      H9c2 myocardial cells were cultured and subjected to MTT and (3)H-thymidine
      incorporation assays for proliferation detection. Luciferase reporter gene and
      Western blot assays were used to detect the transcription and protein expression
      of c-jun. In addition, the activities of ERK5 and ERK1 were determined by Western
      blot assay. The subcellular distribution of ERK5 and ERK1 was analyzed by
      confocal microscopy. It was shown that atRA (0.05 microM) facilitated the
      proliferation of H9c2 myocardial cells and increased the transcription and
      protein expression of c-jun. Inhibition of ERK5 significantly decreased atRA
      induced pJluc expression (P<.01). The activity of ERK5 but not ERK1 was induced
      by atRA. Furthermore, atRA promoted the nuclear translocation of ERK5 but not
      ERK1. These results suggest that ERK5 pathway may be involved in the process that
      atRA regulates proliferation in the developing heart.

PMID- 17509855
TI  - Increased oxidative properties of gastrocnemius in rats fed on a high-protein
      diet.
AB  - It has been reported that a high-protein diet containing 30% protein partially
      prevents skeletal muscle fiber type changes (slow to fast) under atrophic
      conditions. No studies have examined the detailed effects of dietary protein on
      the oxidative properties of skeletal muscles. We examined the effects of a high
      protein diet on the oxidative properties of rat gastrocnemius. Nineteen male
      Wistar rats (5 weeks old) were divided into the following groups: (1) control
      diet [15% protein (15P); n=6], (2) 25% protein (25P; n=6) and (3) 35% protein
      (35P, n=7). After 4 weeks of feeding, succinate dehydrogenase (SDH) staining and
      myosin isoforms were analyzed, along with the expression of the major
      transcription-related molecules for fast-to-slow fiber transition, i.e.,
      peroxisome proliferator-activated receptor gamma coactivator (PGC) 1 alpha and
      nuclear factor of activated T cells (NFAT) c1. SDH staining showed that the
      relative oxidative fiber content of the 35P group was significantly higher than
      that of the 15P group. The slow myosin heavy chain content in the 35P group was
      also higher than that in the 15P group. Western blotting analysis showed that the
      gastrocnemius of the 35P group contained significantly higher amounts of PGC1
      alpha and NFATc1 than that of the 15P group. We conclude that a high-protein
      diet, i.e., 35% protein, induces oxidative properties in rat gastrocnemius.

PMID- 17509856
TI  - A simple rapid immunoassay for S-adenosylhomocysteine in plasma.
AB  - The measurement of plasma S-adenosylhomocysteine is a more sensitive indicator of
      the risk for vascular disease than is plasma homocysteine. Because the level of S
      adenosylhomocysteine is normally in the nanomolar range, it has been difficult to
      measure and necessitated the development of complex fluorometric and mass
      spectrophotometric methods. We have now adapted an existing immunoassay used for
      the measurement of homocysteine to the measurement of S-adenosylhomocysteine in
      plasma. This assay is sensitive down to the level of less than 0.1 pmol, and
      there is no interference by S-adenosylmethionine. The assay is carried out in
      microplates, allows the measurement of 12 samples per plate and can easily be
      carried out in a 4-h period. The method is applicable to plasma samples having S
      adenosylhomocysteine concentrations ranging from 10 to 150 nM without dilution.
      The mean value for 16 normal subjects by this method was 18.9+/-1.4 nM (S.E.M.),
      compared with 17.8+/-1.4 nM obtained by a previously described method using two
      high-performance liquid chromatography columns with fluorescence derivatization.
      Mean values for seven cirrhotic patients were 46.5+/-3.3 nM by this new method
      compared with 44.6+/-5.3 by the former method. The ease and speed of this method
      should allow the widespread measurement of this important metabolite in
      laboratories without access to sophisticated equipment.

PMID- 17509857
TI  - Low dietary inorganic phosphate affects the brain by controlling apoptosis, cell
      cycle and protein translation.
AB  - Inorganic phosphate (Pi) plays a key role in diverse physiologic functions. In a
      previous study, we showed that high dietary Pi perturbs brain growth through
      Akt/ERK signaling in developing mice. However, no study has investigated the
      response of the brain to low dietary Pi. In this study, we addressed this
      question by studying the effects of low dietary Pi on the cerebrum of developing
      mice. Two-week-old weaned mice were fed with a low phosphate diet for 4 weeks. At
      the end of the study, their cerebrum was dissected and signals important for
      protein translation, apoptosis and cell cycle were examined. The low phosphate
      diet did not cause physiologically significant changes; it increased the protein
      expression of phosphatase and tensin homolog deleted on chromosome 10 but
      decreased Akt activity. In addition, expression of eukaryotic translation
      initiation factor binding protein coupled with increased complex formation of
      eukaryotic translation initiation factor 4E/eukaryotic translation initiation
      factor binding protein 1 was induced in the cerebrum by low phosphate, leading to
      reduced cap-dependent protein translation. Finally, low phosphate facilitated
      apoptosis and suppressed signals important for the cell cycle in the cerebrum of
      dual-luciferase reporter mice. In summary, our results showed that a low
      phosphate diet affects the brain by controlling protein translation, apoptosis
      and cell cycle in developing mice. Our results support the hypothesis that Pi
      works as a stimulus capable of increasing or decreasing several pivotal genes for
      normal development and suggest that regulation of Pi consumption is important in
      maintaining a healthy life.

PMID- 17509859
TI  - Influence of waste input and combustion technology on MSWI bottom ash quality.
AB  - The waste input and the process technology of waste incineration plants appear to
      have a great influence on bottom ash quality. To better understand how these
      parameters can affect the characteristics of residues, bottom ash from six plants
      were tested and compared in this study. Bottom ash physico-chemical
      characteristics were investigated by chemical analyses, and leaching tests. In
      order to understand their long-term behavior, accelerated ageing experiments and
      biodegradation tests were also performed. The whole analyses gave complementary
      information. It was shown that the six samples do have different properties.
      Waste inputs have a great influence on Cl and S content in bottom ash, as well as
      on the Ca/Si ratio. The importance of this ratio on the carbonation process has
      been demonstrated. Combustion parameters have an influence on the quantity and
      mobility of the residual organic matter.

PMID- 17509858
TI  - Effects of dietary factors on iron uptake from ferritin by Caco-2 cells.
AB  - Biofortification of staple foods with iron (Fe) in the form of ferritin (Ft) is
      now possible, both by conventional plant breeding methods and transgenic
      approaches. Ft-Fe from plants and animals is absorbed well (25-30%) by human
      subjects, but little is known about dietary factors affecting its absorption. We
      used human intestinal Caco-2 cells and compared Fe absorption from animal Ft and
      FeSO4 to determine the effects of inhibitors and enhancers, such as phytic acid,
      ascorbic acid, tannic acid, calcium and heme. When postconfluent cells were
      coincubated with 59Fe-labeled (1 microM) FeSO4 and dietary factors, at different
      molar ratios of dietary factor to Fe (phytic acid:Fe, 10:1; ascorbic acid:Fe,
      50:1; tannic acid:Fe, 50:1; calcium:Fe, 10:1 and hemin:Fe, 10:1), all inhibited
      uptake from FeSO4, except ascorbate, confirming earlier studies. In contrast,
      these dietary factors had little or no effect on Fe uptake from undigested Ft or
      Ft digested in vitro at pH 4, except tannins. However, results after in vitro
      digestion of Ft at pH 2 were similar to those obtained for FeSO4. These results
      suggest that Fe uptake occurs from both undigested as well as digested Ft but,
      possibly, via different mechanisms. The Fe-Ft stability shown here could minimize
      Fe-induced oxidation of Fe-supplemented food products.

PMID- 17509860
TI  - In situ nitrogen removal from leachate by bioreactor landfill with limited
      aeration.
AB  - The feasibility of simultaneous nitrification and denitrification in a bioreactor
      landfill with limited aeration was assessed. Three column reactors, simulating
      bioreactor landfill operations under anaerobic condition (as reference),
      intermittent forced aeration and enhanced natural aeration were hence
      established, where aerated columns passed through two phases, i.e., fresh
      landfill and well-decomposed landfill. The experimental results show that limited
      aeration decreased nitrogen loadings of leachate distinctly in the fresh
      landfill. In the well-decomposed landfill, the NH(4)(+)-N of the input leachate
      could be nitrified completely in the aerated landfill columns. The nitrifying
      loadings of the column cross section reached 7.9 g N/m(2)d and 16.9 g N/m(2)d in
      the simulated landfill columns of intermittent forced aeration and enhanced
      natural aeration, respectively. The denitrification was influenced by oxygen
      distribution in the landfill column. Intermittent existence of oxygen in the
      landfill with the intermittent forced aeration was favorable to denitrify the
      NO(2)(-)-N and NO(3)(-)-N, indicated by the high denitrification efficiency
      (>99%) under the condition of BOD(5)/TN of more than 5.4 in leachate; locally
      persistent existence of oxygen in the landfill with enhanced natural aeration
      could limit the denitrification, indicated by relatively low denitrification
      efficiency of about 75% even when the BOD(5)/TN in leachate had an average of
      7.1.

PMID- 17509861
TI  - Swedish recovered wood waste: linking regulation and contamination.
AB  - In Sweden, large amounts of wood waste are generated annually from construction
      and demolition activities, but also from other discarded products such as
      packaging and furniture. A large share of this waste is today recovered and used
      for heat production. However, previous research has found that recovered wood
      waste (RWW) contains hazardous substances, which has significant implications for
      the environmental performance of recycling. Improved sorting is often suggested
      as a proper strategy to decrease such implications. In this study, we aim to
      analyse the impacts of waste regulation on the contamination of RWW. The
      occurrence of industrial preservative-treated wood, which contains several
      hazardous substances, was used as an indicator for contamination. First the
      management of RWW during 1995-2004 was studied through interviews with involved
      actors. We then determined the occurrence of industrial preservative-treated wood
      in RWW for that time period for each supplier (actor). From the results, it can
      be concluded that a substantially less contaminated RWW today relies on extensive
      source separation. The good news is that some actors, despite several obstacles
      for such upstream efforts, have already today proved capable of achieving
      relatively efficient separation. In most cases, however, the existing waste
      regulation has not succeeded in establishing strong enough incentives for less
      contaminated waste in general, nor for extensive source separation in particular.
      One important factor for this outcome is that the current market forces encourage
      involved actors to practice weak quality requirements and to rely on end-of-pipe
      solutions, rather than put pressure for improvements on upstream actors. Another
      important reason is that there is a lack of communication and oversight of
      existing waste regulations. Without such steering mechanisms, the inherent
      pressure from regulations becomes neutralized.

PMID- 17509862
TI  - An integrated dielectrophoretic quartz crystal microbalance (DEP-QCM) device for
      rapid biosensing applications.
AB  - A factor limiting the detection time of biological particles using a quartz
      crystal microbalance (QCM) system is the kinetics of the particles arriving
      within the sensing region of the crystal surface. A device has been developed
      which, for the first time, combines ac electro-kinetic particle manipulation with
      simultaneous acoustic sensing on an electrode surface. We have termed this device
      a dielectrophoretic quartz crystal microbalance (DEP-QCM). Particles within the
      system are rapidly driven by electro-hydrodynamic and dielectrophoretic forces on
      to the crystal surface. Frequency shift analysis of mass-loaded DEP-QCM, induced
      by fluid motion, has shown significant improvements in rates of detection based
      on particle concentration, with steady-state responses established by a factor of
      five times faster than other quartz crystal microbalance surface loading
      techniques described in the literature. Comparisons of the static fluid case for
      QCM devices revealed that particles with a concentration of less than 10(8) nano
      spheres/ml could not be detected within a 1h time period when allowed to
      sediment.

PMID- 17509863
TI  - Integrating ecology into biotechnology.
AB  - New high-throughput culture-independent molecular tools are allowing the
      scientific community to characterize and understand the microbial communities
      underpinning environmental biotechnology processes in unprecedented ways. By
      creatively leveraging these new data sources, microbial ecology has the potential
      to transition from a purely descriptive to a predictive framework, in which
      ecological principles are integrated and exploited to engineer systems that are
      biologically optimized for the desired goal. But to achieve this goal, ecology,
      engineering and microbiology curricula need to be changed from the very root to
      better promote interdisciplinarity.

PMID- 17509864
TI  - Mixed culture biotechnology for bioenergy production.
AB  - Mixed culture biotechnology (MCB) could become an attractive addition or
      alternative to traditional pure culture based biotechnology for the production of
      chemicals and/or bioenergy. On the basis of ecological selection principles, MCB
      based processes can be established that generate a narrow product spectrum from a
      mixed substrate. Three example processes are briefly discussed in this paper:
      anaerobic digestion aimed at the production of methane-containing biogas, mixed
      culture fermentation for the production of solvents or biohydrogen, and a two
      step process for the production of polyhydroxyalkanoates. These examples give an
      idea of the potential contribution of mixed culture biotechnology to sustainable
      production of bioenergy from waste.

PMID- 17509865
TI  - Guidelines for use of recombinant factor VIIa in life-threatening post-partum
      haemorrhage.

PMID- 17509867
TI  - Epidural analgesia for parturients with type 1 von Willebrand disease.
AB  - BACKGROUND: Epidural analgesia is usually contraindicated in von Willebrand
      disease. However, in type 1, the increased synthesis of von Willebrand factor
      (vWF) and factor VIII (FVIII:C) during pregnancy can lead to a correction of
      biological abnormalities and may allow epidural analgesia to be performed for
      delivery. METHODS: The clinical files of pregnant patients with type 1 von
      Willebrand disease who delivered in our tertiary perinatal unit were reviewed.
      The time profile of hemostasis abnormalities during pregnancy, technical features
      and complication of epidural analgesia when performed were recorded. RESULTS:
      Sixteen pregnancies (13 patients) were included. Mean (+/- SD) concentrations of
      FVIII:C, vWAg, and vWRCo before pregnancy (42+/-12, 46+/-8, 42+/-10 units/dL,
      respectively) increased to normal values in all cases at term (142+/-42, 142+/
      61, 142+/-79 units/dL, respectively). Nine epidurals (6 patients) were performed
      without complication. Three parturients did not receive epidural analgesia
      despite normal biological hemostasis because the anesthesiologist was still
      reluctant to provide it. Four other parturients had PFA-100 closure times (n=3)
      or a bleeding time that remained prolonged; epidural analgesia was not performed
      for these cases. CONCLUSIONS: vWF and FVIII:C increased to normal values in all
      cases at term in these parturients with type 1 von Willebrand disease. Epidural
      analgesia, when performed for labor, was uncomplicated. However, platelet
      aggregation tests with PFA-100 unmasked unexpected, persistent abnormalities. The
      value of this test for clinical decision making remains to be determined by
      further prospective studies.

PMID- 17509868
TI  - Complete failure of spinal anaesthesia in obstetrics.
AB  - Intrathecal anaesthesia, either as a single shot-spinal or as part of a combined
      spinal-epidural technique, is now widely accepted as the management of choice for
      caesarean section. It generally produces rapid and predictable anaesthesia, yet
      occasionally fails for no apparent reason. Four case reports of seemingly
      inexplicable complete failure of intrathecal anaesthesia are presented, together
      with a literature review of other cases and possible causes of the failure, which
      include anatomical abnormality, drug failure and management failure.

PMID- 17509869
TI  - Efficacy of patient-controlled epidural analgesia after initiation with epidural
      or combined spinal-epidural analgesia.
AB  - BACKGROUND: The aim of the present study was to compare the efficacy of patient
      controlled epidural analgesia after initiation with either epidural or combined
      spinal-epidural analgesia. METHODS: Forty ASA I parturients at 37-42 weeks'
      gestation and cervical dilatation <6 cm were randomly allocated to receive either
      epidural analgesia (group EA) or combined spinal-epidural analgesia (group CSEA).
      Analgesia was initiated with a 7-mL epidural bolus 0.1% bupivacaine containing
      fentanyl 50 mug (group EA, n=20) or with intrathecal fentanyl 20 mug (group CSEA,
      n=20). In both groups, analgesia was provided by a 5-mL bolus on demand via PCEA
      with a 10-min lock-out interval and a 15-mL/h limit. RESULTS: No significant
      differences were observed in the rate of cervical dilatation, delivery type or
      duration of delivery between the groups. The time to first analgesic demand was
      shorter in the CSEA than in the EA group. Total bupivacaine dose was comparable
      in both groups, but total fentanyl dose in group CSEA was significantly lower
      than that of group EA because of the initial dose used for the induction of EA
      and CSEA. The incidence of pruritus in group CSEA was significantly higher than
      in group EA. CONCLUSION: Both regional analgesia techniques followed by demand
      only PCEA provided efficient pain relief for labor without changing the duration
      of labor or rate of cesarean section.

PMID- 17509870
TI  - Blood conservation techniques in obstetrics: a UK perspective.
AB  - In the UK, maternal mortality due to haemorrhage appears to be rising, with
      obstetric haemorrhage accounting for 3-4% of the red cells transfused. Allogeneic
      blood transfusion carries risks such as administration errors, transmitted
      infections and immunological reactions. The supply of blood is decreasing, partly
      due to the exclusion of donors who have themselves received a blood transfusion
      since 1980, in order to stop transmission of variant-Creutzfeldt-Jakob disease.
      The cost of blood is significantly increasing, partly because it is now leucocyte
      depleted to minimize viral transmission. Various blood conservation techniques
      can reduce exposure to allogeneic blood thereby reducing risk and conserving the
      blood supply. These include preoperative autologous donation, acute normovolaemic
      haemodilution and intra-operative cell salvage. Preoperative autologous donation
      may produce anaemia, does not eliminate transfusion risk, cannot be used in an
      emergency and is not acceptable to Jehovah's Witnesses. It should be reserved for
      exceptional circumstances (rare blood type or unusual antibodies). Acute
      normovolaemic haemodilution may induce anaemia and cardiac failure and cannot be
      used in an emergency. It may have a limited role in combination with other
      techniques. Intra-operative cell salvage is more effective and useful in
      obstetrics than the other techniques, overcomes their shortcomings and is
      endorsed by CEMACH, OAA/AAGBI Guidelines, the National Blood Service and NICE.

PMID- 17509871
TI  - Continuous spinal analgesia in parturients with severe heart disease.

PMID- 17509873
TI  - Glutamate and monoamine transporters: new visions of form and function.
AB  - Neurotransmitters are rapidly removed from the extracellular space primarily
      through the actions of plasma membrane transporters. This uptake process is not
      only essential in the termination of neurotransmission but also serves to
      replenish intracellular levels of transmitter for further release.
      Neurotransmitter transporters couple the inward movement of substrate to the
      movement of Na(+) down a concentration gradient and, in addition to their
      transport function, some carriers also display channel-like activities. Five
      Na(+)/K(+)-dependent glutamate transporter subtypes belong to the solute carrier
      1 (SLC1) family and a second family, SLC6, encompasses the Na(+)/Cl(-)-dependent
      transporters for dopamine, 5-hydroxytryptamine (serotonin), noradrenaline, GABA
      and glycine. Recent advances, including high-resolution structures from both
      families, are now providing new insights into the molecular determinants that
      contribute to substrate translocation and ion channel activities. Other
      influential studies have explored how cellular regulatory mechanisms modulate
      transporter function, and how the different functions of the carrier shape the
      patterns of neurotransmitter signaling. This review focuses on recent studies of
      glutamate and monoamine transporters as prototypes of the two carrier families.

PMID- 17509874
TI  - Signalling mechanisms.

PMID- 17509875
TI  - Hodgkin's lymphoma in children aged 5 years or less - the United Kingdom
      experience.
AB  - PURPOSE: The aim of this study is to describe the natural history of Hodgkin's
      Lymphoma (HL) in a large unselected group of children aged 5 years or below at
      diagnosis, who were treated on a standard treatment programme in the United
      Kingdom between 1982 and 2000. METHODS: Eighty-one unselected children with HL
      aged 5 years or under at diagnosis, treated on the United Kingdom Children's
      Cancer Study Group (UKCCSG) Hodgkin's trials HD1 (1982-1992) and HD2 (1992-2000),
      were included in the study. RESULTS: Sixty-one patients (81%) presented with
      early stage disease (n=66). Fifty-three patients (65%) received combination
      chemotherapy, 28 (34%) received involved field radiotherapy (IF-RT) and 4
      patients were treated with combined modality therapy. Eighteen children relapsed
      after primary therapy. CONCLUSIONS: Children treated with IF-RT had a higher rate
      of primary treatment failures as well as increased late treatment-related
      morbidity.

PMID- 17509876
TI  - Clinical implication of estrogen-related receptor (ERR) expression in ovarian
      cancers.
AB  - The expression of estrogen receptor (ER)alpha and ERbeta mRNAs did not show any
      specific manner according to clinical backgrounds in ovarian cancers. On the
      other hand, the levels of estrogen-related receptor (ERR)alpha mRNA increased
      with clinical stages regardless of histopathological types in ovarian cancers.
      However, ERRbeta and ERRgamma mRNA levels were extremely low to determine
      reliably. ERRalpha can bind to the steroid receptor coactivator family without
      any ligands, and drive transcription activity of the target genes. The manner of
      ERR and ER gene expressions might show an independent usage of common cofactors.
      It is speculated that the up regulation of ERRalpha might be related to
      advancement of ovarian cancers regardless of plausible interaction via cofactors
      regulated by ERs. Although ERRalpha is not directly related to growth of ovarian
      cancer, ERRalpha is a candidate for prognostic factors for ovarian cancer.

PMID- 17509877
TI  - Production of protease and lipase by solvent tolerant Pseudomonas aeruginosa PseA
      in solid-state fermentation using Jatropha curcas seed cake as substrate.
AB  - Deoiled Jatropha seed cake was assessed for its suitability as substrate for
      enzyme production by solid-state fermentation (SSF). Solvent tolerant Pseudomonas
      aeruginosa PseA strain previously reported by us was used for fermentation. The
      seed cake supported good bacterial growth and enzyme production (protease, 1818
      U/g of substrate and lipase, 625 U/g of substrate) as evident by its chemical
      composition. Maximum protease and lipase production was observed at 50% substrate
      moisture, a growth period of 72 and 120 h, and a substrate pH of 6.0 and 7.0,
      respectively. Enrichment with maltose as carbon source increased protease and
      lipase production by 6.3- and 1.6-fold, respectively. Nitrogen supplementation
      with peptone for protease and NaNO(3) for lipase production also enhanced the
      enzyme yield reaching 11,376 U protease activity and 1084 U lipase activity per
      gram of Jatropha seed cake. These results demonstrated viable approach for
      utilization of this huge biomass by solid-state fermentation for the production
      of industrial enzymes. This offers significant benefit due to low cost and
      abundant availability of cake during biodiesel production.

PMID- 17509878
TI  - New syntheses of tetrazolylmethylphenylalanine and O-malonyltyrosine as pTyr
      mimetics for the design of STAT3 dimerization inhibitors.
AB  - Investigation within the pTyr-binding pocket of the STAT3 SH2 domain led us to
      develop a novel synthesis of two pTyr mimetics, l-tetrazolylmethylphenylalanine
      (l-Tmp) and l-O-malonyltyrosine (l-OMT), that were next incorporated in a high
      affinity ligand of STAT3 SH2 domain. Biological evaluation of peptidomimetics on
      STAT3 dimerization identified l-OMT as the first non-phosphorus pTyr mimetic so
      far reported against STAT3 SH2 domain, harboring an activity similar to that of
      the Pmp-containing reference peptidomimetic.

PMID- 17509879
TI  - Factors determining outcome after third line chemotherapy for metastatic breast
      cancer.
AB  - Patients with metastatic breast cancer (MBC) are increasingly offered third line
      chemotherapy. We have reviewed the response rate (RR), time to progression (TTP)
      and survival of 149 patients in this setting and have investigated factors that
      influence their outcome. The RR, TTP and survival were 30%, 4 and 8 months,
      respectively, and should serve as a benchmark for future studies. Response to
      previous chemotherapy was the only independent variable predicting RR, TTP and
      survival, p=0.025, 0.04 and 0.004, respectively. Thirty-two percent of patients
      did not respond to the first two lines of chemotherapy and had a lower RR and a
      significantly shorter TTP and survival. In conclusion, third line chemotherapy
      for MBC is sometimes effective in patients who have responded to previous
      chemotherapy. Patients who do not respond to the first two lines of chemotherapy
      should be considered for clinical trials or supportive care.

PMID- 17509880
TI  - Evidence-based management of Mastalgia: a meta-analysis of randomised trials.
AB  - Several agents have been utilised for therapy of mastalgia based on data from
      small trials. No meta-analysis of trials on mastalgia exists. We have conducted a
      meta-analysis on trials on mastalgia published in the English language. Study was
      restricted to randomised controlled trials comparing Bromocriptine, Danazol,
      Evening primrose oil (EPO) and Tamoxifen with placebo. The analysis was carried
      out on the REVMAN statistical package. Weighted mean difference in the pain score
      in favour of Bromocriptine was -16.31(95% CI -26.35 to -6.27). Danazol produced a
      significant benefit with a mean pain score difference -20.23(95% CI -28.12 to 
      12.34). EPO did not offer any advantage over placebo in pain relief, mean pain
      score difference being -2.78 (95% CI -7.97 to 2.40). Tamoxifen achieved a
      relative risk (RR) of pain relief of 1.92 (95% CI 1.42-2.58). Tamoxifen is
      associated with least side effects and should be the drug of first choice.

PMID- 17509881
TI  - C. elegans CUL-4 prevents rereplication by promoting the nuclear export of CDC-6
      via a CKI-1-dependent pathway.
AB  - Genome stability requires that genomic DNA is replicated only once per cell
      cycle. The replication-licensing system ensures that the formation of
      prereplicative complexes is temporally separated from the initiation of DNA
      replication [1-4]. The replication-licensing factors Cdc6 and Cdt1 are required
      for the assembly of prereplicative complexes during G1 phase. During S phase,
      metazoan Cdt1 is targeted for degradation by the CUL4 ubiquitin ligase [5-8], and
      vertebrate Cdc6 is translocated from the nucleus to the cytoplasm [9, 10].
      However, because residual vertebrate Cdc6 remains in the nucleus throughout S
      phase [10-13], it has been unclear whether Cdc6 translocation to the cytoplasm
      prevents rereplication [1, 2, 14]. The inactivation of C. elegans CUL-4 is
      associated with dramatic levels of DNA rereplication [5]. Here, we show that C.
      elegans CDC-6 is exported from the nucleus during S phase in response to the
      phosphorylation of multiple CDK sites. CUL-4 promotes the phosphorylation and
      subsequent translocation of CDC-6 via negative regulation of the CDK-inhibitor
      CKI-1. Rereplication can be induced by coexpression of nonexportable CDC-6 with
      nondegradable CDT-1, indicating that redundant regulation of CDC-6 and CDT-1
      prevents rereplication. This demonstrates that CDC-6 translocation is critical
      for preventing rereplication and that CUL-4 independently controls both
      replication-licensing factors.

PMID- 17509882
TI  - Kinetochore dynein is required for chromosome motion and congression independent
      of the spindle checkpoint.
AB  - During mitosis, the motor molecule cytoplasmic dynein plays key direct and
      indirect roles in organizing microtubules (MTs) into a functional spindle. At
      this time, dynein is also recruited to kinetochores, but its role or roles at
      these organelles remain vague, partly because inhibiting dynein globally disrupts
      spindle assembly [1-4]. However, dynein can be selectively depleted from
      kinetochores by disruption of ZW10 [5], and recent studies with this approach
      conclude that kinetochore-associated dynein (KD) functions to silence the spindle
      assembly checkpoint (SAC) [6]. Here we use dynein-antibody microinjection and the
      RNAi of ZW10 to explore the role of KD in chromosome behavior during mitosis in
      mammals. We find that depleting or inhibiting KD prevents the rapid poleward
      motion of attaching kinetochores but not kinetochore fiber (K fiber) formation.
      However, after kinetochores attach to the spindle, KD is required for stabilizing
      kinetochore MTs, which it probably does by generating tension on the kinetochore,
      and in its absence, chromosome congression is defective. Finally, depleting KD
      reduces the velocity of anaphase chromosome motion by approximately 40%, without
      affecting the rate of poleward MT flux. Thus, in addition to its role in
      silencing the SAC, KD is important for forming and stabilizing K fibers and in
      powering chromosome motion.

PMID- 17509883
TI  - Nonredundant functions of Kinesin-13s during meiotic spindle assembly.
AB  - Spatiotemporal control of microtubule depolymerization during cell division
      underlies the construction and dynamics of mitotic and meiotic spindles. Owing to
      their potent ability to disassemble microtubules, Kinesin-13s constitute an
      important class of microtubule destabilizing factors. Unfertilized Xenopus eggs,
      similar to other metazoan cells, contain the prototypical Kinesin-13 MCAK as well
      as a second family member, XKIF2. Here, we compare the roles of MCAK and XKIF2
      during spindle assembly in Xenopus extracts. We find that although MCAK and XKIF2
      have similar localization and biochemical properties, XKIF2 is not required for
      spindle assembly and, further, cannot substitute for MCAK. Altering dosage of the
      two kinesins demonstrates that spindle length is exquisitely sensitive to MCAK
      concentration but not XKIF2 concentration. Finally, we demonstrate that the rate
      of poleward microtubule flux in Xenopus-extract spindles is unaffected by XKIF2
      depletion and is only modestly sensitive to reduction of MCAK action. We suggest
      that, in contrast to models proposed for mammalian somatic cell and embryonic
      Drosophila spindles, Kinesin-13s do not play a central role in poleward flux by
      depolymerizing minus ends. Rather, MCAK, but not XKIF2, plays a central role in
      regulating dynamic instability of plus ends and controls spindle length by that
      mechanism.

PMID- 17509884
TI  - Proprioceptive contribution of postural control as assessed from very slow
      oscillations of the support in healthy humans.
AB  - Maintaining erect human posture depends on graviceptive information. This can
      come from at least of three origins: vestibular, visual and somaesthetic. We
      hypothesize here that subject's use proprioception rather than visual or
      vestibular cues for their control of upright body posture and this even when
      subjects stand on a tilting body support surface. In order to find experimental
      evidence for this hypothesis, we exclude in our experiments visual cues (eyes
      close) and by keeping frequency and amplitude of the tilt stimulus so low that it
      would be below the detection threshold for vestibular semi-circular canal
      stimuli. The orientations of body segments were analysed during various phases of
      the perturbation cycle. Segmental stabilisations were defined in terms of both
      the global anchoring index calculated during the whole perturbation cycle and an
      appropriate sequential anchoring index calculated during various phases in the
      perturbation cycle. We show that subjects tend to align their bodies with the
      space vertical and do so better for their heads than for their upper bodies and
      lower bodies. A further finding is that stabilisation is related to the tilt
      stimulus in the form that it is minimal at the turning points of the tilt, where
      peak tilt velocity is minimal with the sinusoidal stimulus used. These finding
      suggest first that proprioceptive cues are predominant in the control of body
      orientation in quasi-static condition and second that the head and trunk
      stabilisation strategies used as the basis of postural control depend on the
      properties of the moving support.

PMID- 17509885
TI  - Qualitative and quantitative descriptions of glenohumeral motion.
AB  - Joint modelling plays an important role in qualitative and quantitative
      descriptions of both normal and abnormal joints, as well as predicting outcomes
      of alterations to joints in orthopaedic practice and research. Contemporary
      efforts in modelling have focussed upon the major articulations of the lower
      limb. Well-constrained arthrokinematics can form the basis of manageable kinetic
      and dynamic mathematical predictions. In order to contain computation of shoulder
      complex modelling, glenohumeral joint representations in both limited and
      complete shoulder girdle models have undergone a generic simplification. As such,
      glenohumeral joint models are often based upon kinematic descriptions of
      inadequate degrees of freedom (DOF) for clinical purposes and applications.
      Qualitative descriptions of glenohumeral motion range from the parody of a hinge
      joint to the complex realism of a spatial joint. In developing a model, a clear
      idea of intention is required in order to achieve a required application.
      Clinical applicability of a model requires both descriptive and predictive output
      potentials, and as such, a high level of validation is required. Without
      sufficient appreciation of the clinical intention of the arthrokinematic
      foundation to a model, error is all too easily introduced. Mathematical
      description of joint motion serves to quantify all relevant clinical parameters.
      Commonly, both the Euler angle and helical (screw) axis methods have been applied
      to the glenohumeral joint, although concordance between these methods and
      classical anatomical appreciation of joint motion is limited, resulting in
      miscommunication between clinician and engineer. Compounding these
      inconsistencies in motion quantification is gimbal lock and sequence dependency.

PMID- 17509886
TI  - Pyrene-modified guanosine as fluorescent probe for DNA modulated by charge
      transfer.
AB  - 8-(Pyren-1-yl)-2'-deoxyguanosine (Py-G) was incorporated synthetically as a
      modified DNA base and optical probe into oligonucleotides. A variety of Py-G
      modified DNA duplexes have been investigated by methods of optical spectroscopy.
      The DNA duplex hybridization can be observed by both fluorescence and absorption
      spectroscopy since the Py-G group exhibits altered properties in single strands
      versus double strands for both spectroscopy methods. The fluorescence enhancement
      upon DNA hybridization can be improved significantly by the presence of 7
      deazaguanin as an additional modification and charge acceptor three bases away
      from the Py-G modification site. Moreover, Py-G in DNA can be applied as a
      photoinducable donor for charge transfer processes when indol is present as an
      artificial DNA base and charge acceptor. Correctly base-paired duplexes can be
      discriminated from mismatched ones by comparison of their fluorescence quenching.

PMID- 17509887
TI  - Synthesis of penaresidin derivatives and its biological activity.
AB  - A series of stereoisomers for the azetidine ring of penaresidin B was synthesized
      and their cytotoxic and antimicrobial activities were evaluated. Among six
      synthetic isomers 1-6, isomers 4 and 5 showed relatively potent cytotoxic
      activity against A549 (lung) and HT29 (colon) tumor cells as well as
      antibacterial activity.

PMID- 17509889
TI  - Soft X-ray spectromicroscopy of phase-change microcapsules.
AB  - A synchrotron-based scanning transmission X-ray microscope (STXM) is used to
      investigate Micronal phase-change microcapsules. Prolonged X-ray illumination of
      the specimen leads to the breaking of the microcapsules' protective polymer shell
      and a partial separation of the core-shell species occurs. The paraffin wax and
      acrylic polymer components are characterized by carbon K-edge near X-ray edge
      absorption fine structure (NEXAFS) spectroscopy and components distribution
      mapping of the beam-damaged specimen is performed.

PMID- 17509890
TI  - Responses of the toxic cyanobacterium Microcystis aeruginosa to iron and humic
      substances.
AB  - Iron is an essential element to marine biota. Different types of dissolved
      organic matter (DOM), such as humic substances have impacts on the marine coastal
      waters iron chemistry. The aim of the study was to examine how the presence of
      humic substances (both aquatic and sedimentary) may affect iron bioavailability
      to the bloom-forming cyanobacterium Microcystis aeruginosa Kutzing incubated on
      standard and modified mineral BG-11 media. The final iron concentrations in the
      growth media ranged from 0.1 to 100microM. The results demonstrate that both the
      growth rate and the concentration of chlorophyll a in cultures of M. aeruginosa
      are limited by insufficient (<10microM) Fe concentrations. The addition of
      aquatic humic substances in the presence of iron in concentrations <0.1microM
      increased the optical density 25-fold, and the production of chlorophyll a 15
      fold as compared with the cultures exposed to iron only at the same
      concentration. Sedimentary humic acids in the presence of iron at a concentration
      of 10microM reduced the growth and production of chlorophyll a by 50% as compared
      to the cultures exposed to iron only at the same concentration. Possible
      mechanisms of humic substances - metal ion - alga interactions are discussed. It
      is suggested that aquatic humic substances could be of great importance in the
      formation of cyanobacteria blooms.

PMID- 17509888
TI  - O2-acetoxymethyl-protected diazeniumdiolate-based NSAIDs (NONO-NSAIDs):
      synthesis, nitric oxide release, and biological evaluation studies.
AB  - A novel group of O2-acetoxymethyl-protected diazeniumdiolate-based non-steroidal
      anti-inflammatory prodrugs (NONO-NSAIDs) were synthesized by esterifying the
      carboxylate group of aspirin, ibuprofen, or indomethacin with O2-acetoxymethyl 1
      [N-(2-hydroxyethyl)-N-methylamino]diazeniumdiolate. The resulting nitric oxide
      (*NO)-releasing prodrugs (7-9) did not exhibit in vitro cyclooxygenase (COX)
      inhibitory activity against the COX-1 and COX-2 isozymes (IC50s>100 microM). In
      contrast, prodrugs 7 and 8 significantly decreased carrageenan-induced rat paw
      edema showing enhanced in vivo anti-inflammatory activities (ID50's=552 and 174
      micromol/kg, respectively) relative to those of the parent NSAIDs aspirin
      (ID50=714 micromol/kg) and ibuprofen (ID50=326 micromol/kg). The rate of porcine
      liver esterase-mediated *NO release from prodrugs 7-9 (2 mol of *NO/mol of test
      compound in 0.6-6.5 min) was substantially higher compared to that observed
      without enzymatic catalysis (about 1 mol of *NO/mol of test compound in 40-48 h).
      These incubation studies suggest that both *NO and the parent NSAID would be
      released upon in vivo activation (hydrolysis) by esterases. Data acquired in an
      in vivo ulcer index (UI) assay showed that NONO-aspirin (UI=0.8), NONO
      indomethacin (UI=1.3), and particularly NONO-ibuprofen (UI=0) were significantly
      less ulcerogenic compared to the parent drugs aspirin (UI=57), ibuprofen (UI=46)
      or indomethacin (UI=34) at equimolar doses. The release of aspirin and *NO from
      the NONO-aspirin (7) prodrug constitutes a potentially beneficial property for
      the prophylactic prevention of thrombus formation and adverse cardiovascular
      events such as stroke and myocardial infarction.

PMID- 17509891
TI  - Is there any difference in lactate level between washed and unwashed donor blood
      during pediatric cardiopulmonary bypass?

PMID- 17509892
TI  - The intracellular renin-angiotensin system: a new paradigm.
AB  - More than a century after its discovery, the physiological implications of the
      renin-angiotensin system (RAS) continue to expand, with the identification of new
      components, functions and subsystems. These advancements have led to better
      management and understanding of a broad range of cardiovascular and metabolic
      disorders. The RAS has traditionally been viewed as a circulatory system,
      involved in the short-term regulation of volume and blood pressure homeostasis.
      Recently, local RASs have been described as regulators of chronic tissue effects.
      Most recently, studies have provided evidence of a complete, functional RAS
      within cells, described as an 'intracrine' or intracellular system. A more
      comprehensive understanding of the intracellular RAS provides for new strategies
      in system regulation and a more efficacious approach to the management of RAS
      related diseases.

PMID- 17509893
TI  - High-level expression, polyclonal antibody preparation and sub-cellular
      localization analysis of mouse Rhox5 protein.
AB  - Mouse reproductive homeobox on the X chromosome (Rhox) is a novel homeobox gene
      cluster. Rhox5, also called Pem, belongs to the beta subcluster of Rhox. Codon
      analysis indicated that the cDNA contains 16% of codons rarely used in
      Escherichia coli. To achieve high-level expression of Rhox5, the coding sequence
      of Rhox5 was amplified and subcloned into the prokaryotic expression vector
      pET22b (+) in order to produce 6His-tagged fusion protein in the modified BL21
      (DE3) cells, namely Rosetta2 (DE3) cells. The 6His-tagged Rhox5 was expressed
      efficiently in Rosetta2 (DE3), compared with marginal expression in BL21 (DE3).
      The fusion protein amounted to 16% of the total bacterial proteins after
      induction with 0.4mM IPTG for 1.5h at 37 degrees C. After purification, Rhox5
      6His was used to immunize New Zealand white rabbits following standard protocol.
      The homemade antiserum could detect both endogenous Rhox5 protein expressed in
      eukaryotic cells (Cos-7) and exogenous GFP-Rhox5 protein. Furthermore, the
      antiserum was used to determine the localization of Rhox5 in NIH3T3 cells using
      an immunofluorescence technique. The results demonstrated that Rhox5 was
      localized predominantly in the nucleus. Preparation of the anti-Rhox5 polyclonal
      antibody will facilitate further functional study of Rhox5.

PMID- 17509894
TI  - Periplasmic production of native human proinsulin as a fusion to E. coli ecotin.
AB  - Native proinsulin belongs to the class of the difficult-to-express proteins in
      Escherichia coli. Problems mainly arise due to its small size, a high proteolytic
      decay, and the necessity to form a native disulfide pattern. In the present
      study, human proinsulin was produced in the periplasm of E. coli as a fusion to
      ecotin, which is a small periplasmic protein of 16 kDa encoded by the host,
      containing one disulfide bond. The fusion protein was secreted to the periplasm
      and native proinsulin was determined by ELISA. Cultivation parameters were
      studied in parallel batch mode fermentations using E. coli BL21(DE3)Gold as a
      host. After improvement of fed-batch high density fermentation conditions, 153 mg
      fusion protein corresponding to 51.5mg native proinsulin was obtained per L.
      Proteins were extracted from the periplasm by osmotic shock treatment. The fusion
      protein was purified in one step by ecotin affinity chromatography on immobilized
      trypsinogen. After thrombin cleavage of the fusion protein, the products were
      separated by Ni-NTA chromatography. Proinsulin was quantified by ELISA and
      characterized by mass spectrometry. To evaluate the influence of periplasmic
      proteases, the amount of ecotin-proinsulin was determined in E. coli
      BL21(DE3)Gold and in a periplasmic protease deficient strain, E. coli SF120.

PMID- 17509895
TI  - A cross-order integration hypothesis for the neural correlate of consciousness.
AB  - One major problem many hypotheses regarding the neural correlate of consciousness
      (NCC), face is what we might call "the why question": why would this particular
      neural feature, rather than another, correlate with consciousness? The purpose of
      the present paper is to develop an NCC hypothesis that answers this question. The
      proposed hypothesis is inspired by the cross-order integration (COI) theory of
      consciousness, according to which consciousness arises from the functional
      integration of a first-order representation of an external stimulus and a second
      order representation of that first-order representation. The proposal comes in
      two steps. The first step concerns the "general shape" of the NCC and can be
      directly derived from COI theory. The second step is a concrete hypothesis that
      can be arrived at by combining the general shape with empirical considerations.

PMID- 17509896
TI  - Robust controlled functional MRI in alert monkeys at high magnetic field: effects
      of jaw and body movements.
AB  - The use of functional magnetic resonance imaging (fMRI) in alert non-human
      primates is of great potential for research in systems neuroscience. It can be
      combined with invasive techniques and afford better understanding of non
      invasively acquired brain imaging signals in humans. However, the difficulties in
      optimal application of alert monkey fMRI are multi-faceted, especially at high
      magnetic fields where the effects of motion and of changes in B0 are greatly
      amplified. To overcome these difficulties, strict behavioral controls and
      elaborate animal-training are needed. Here, we introduce a number of hardware
      developments, quantify the effect of movements on fMRI data, and present
      procedures for animal training and scanning for well-controlled and artifact
      reduced alert monkey fMRI at high magnetic field. In particular, we describe
      systems for monitoring jaw and body movements, and for accurately tracking eye
      movements. A link between body and jaw movement and MRI image artifacts is
      established, showing that relying on the immobilization of an animal's head is
      not sufficient for high-quality imaging. Quantitative analysis showed that body
      and jaw movement events caused large instabilities in fMRI time series. On
      average, body movement events caused larger instabilities than jaw movement
      events. Residual baseline brain image position and signal amplitude shifts were
      observed after the jaw and body movement events ended. Based on these findings,
      we introduce a novel behavioral paradigm that relies on training the monkeys to
      stay still during long trials. A corresponding analysis method discards all data
      that were not obtained during the movement-free periods. The baseline position
      and amplitude shifts are overcome by motion correction and trial-by-trial signal
      normalization. The advantages of the presented method over conventional scanning
      and analysis are demonstrated with data obtained at 7 T. It is anticipated that
      the techniques presented here will prove useful for alert monkey fMRI at any
      magnetic field.

PMID- 17509897
TI  - An approach to MRI-based dosimetry for transcranial magnetic stimulation.
AB  - A new MRI-based measurement of the magnetic vector field distribution generated
      by a transcranial magnetic stimulation (TMS) probe is introduced in this study.
      Projections of the static magnetic field produced by a DC current in a TMS probe
      onto the axis of the scanner's main field (B0) can be measured using a
      conventional B0 field-mapping technique. The remaining Cartesian components can
      then be calculated from projections obtained at different orientations of the
      sample and probe. The measured static field can then be scaled to calculate the
      effects of a dynamic TMS pulse. This article includes a study demonstrating the
      feasibility of this approach on a phantom and a human subject.

PMID- 17509898
TI  - When thoughts become action: an fMRI paradigm to study volitional brain activity
      in non-communicative brain injured patients.
AB  - The assessment of voluntary behavior in non-communicative brain injured patients
      is often challenging due to the existence of profound motor impairment. In the
      absence of a full understanding of the neural correlates of consciousness, even a
      normal activation in response to passive sensory stimulation cannot be considered
      as proof of the presence of awareness in these patients. In contrast, predicted
      activation in response to the instruction to perform a mental imagery task would
      provide evidence of voluntary task-dependent brain activity, and hence of
      consciousness, in non-communicative patients. However, no data yet exist to
      indicate which imagery instructions would yield reliable single subject
      activation. The aim of the present study was to establish such a paradigm in
      healthy volunteers. Two exploratory experiments evaluated the reproducibility of
      individual brain activation elicited by four distinct mental imagery tasks. The
      two most robust mental imagery tasks were found to be spatial navigation and
      motor imagery. In a third experiment, where these two tasks were directly
      compared, differentiation of each task from one another and from rest periods was
      assessed blindly using a priori criteria and was correct for every volunteer. The
      spatial navigation and motor imagery tasks described here permit the
      identification of volitional brain activation at the single subject level,
      without a motor response. Volunteer as well as patient data [Owen, A.M., Coleman,
      M.R., Boly, M., Davis, M.H., Laureys, S., Pickard J.D., 2006. Detecting awareness
      in the vegetative state. Science 313, 1402] strongly suggest that this paradigm
      may provide a method for assessing the presence of volitional brain activity, and
      thus of consciousness, in non-communicative brain-injured patients.

PMID- 17509899
TI  - Neural substrates of the interaction of emotional stimulus processing and motor
      inhibitory control: an emotional linguistic go/no-go fMRI study.
AB  - Neural substrates of behavioral inhibitory control have been probed in a variety
      of animal model, physiologic, behavioral, and imaging studies, many emphasizing
      the role of prefrontal circuits. Likewise, the neurocircuitry of emotion has been
      investigated from a variety of perspectives. Recently, neural mechanisms
      mediating the interaction of emotion and behavioral regulation have become the
      focus of intense study. To further define neurocircuitry specifically underlying
      the interaction between emotional processing and response inhibition, we
      developed an emotional linguistic go/no-go fMRI paradigm with a factorial block
      design which joins explicit inhibitory task demand (i.e., go or no-go) with task
      unrelated incidental emotional stimulus valence manipulation, to probe the
      modulation of the former by the latter. In this study of normal subjects focusing
      on negative emotional processing, we hypothesized activity changes in specific
      frontal neocortical and limbic regions reflecting modulation of response
      inhibition by negative stimulus processing. We observed common fronto-limbic
      activations (including orbitofrontal cortical and amygdalar components)
      associated with the interaction of emotional stimulus processing and response
      suppression. Further, we found a distributed cortico-limbic network to be a
      candidate neural substrate for the interaction of negative valence-specific
      processing and inhibitory task demand. These findings have implications for
      elucidating neural mechanisms of emotional modulation of behavioral control, with
      relevance to a variety of neuropsychiatric disease states marked by behavioral
      dysregulation within the context of negative emotional processing.

PMID- 17509900
TI  - Nonprosthetic glenoid arthroplasty with humeral hemiarthroplasty and total
      shoulder arthroplasty yield similar self-assessed outcomes in the management of
      comparable patients with glenohumeral arthritis.
AB  - The risk of glenoid component failure has led us to explore nonprosthetic glenoid
      arthroplasty coupled with humeral hemiarthroplasty, the "ream and run" (R&R)
      procedure, for the management of glenohumeral arthritis in active patients. We
      hypothesized that patients having a R&R procedure would have outcomes comparable
      with those of similar patients having a total shoulder arthroplasty (TSA). A case
      matched control study compared 35 consecutive patients (32 men, 3 women) with an
      average age of 56 years, after R&R with matched controls having TSA. The
      respective Simple Shoulder Test (SST) scores for the R&R and TSA groups were 4.5
      and 4.0 before surgery, 7.8 and 9.6 at 12 months, 8.3 and 10.2 at 18 months, 8.9
      and 9.4 at 24 months, 9.4 and 9.6 at 30 months, and 9.5 and 10.0 at 36 months.
      The "ream and run" procedure can offer similar functional recovery to patients
      with total shoulder arthroplasty, although the time to recovery may be longer.

PMID- 17509901
TI  - Islandized hemipectoralis muscle flap for sternoclavicular defect.

PMID- 17509902
TI  - Calcification in superior glenoid labrum of the shoulder: a case report.

PMID- 17509903
TI  - Oxygen free radicals and tendon healing.
AB  - Nitric oxide is a small free radical generated by a family of enzymes, the nitric
      oxide synthases (NOSs). In a series of experiments performed over the last 15
      years, we showed that nitric oxide is induced by all 3 isoforms of NOS during
      tendon healing and that it plays a crucial beneficial role in restoring tendon
      function. In normal tendons, very little NOS activity was found, whereas in
      injured rat and human tendons, NOS activity was expressed in healing fibroblasts
      in a temporal fashion. In healing rat Achilles tendon fibroblasts, the first
      isoform to be expressed was endothelial NOS, followed by inducible NOS and then
      brain or neuronal NOS. Systemic inhibition of NOS activity decreased the cross
      sectional area and mechanical properties of the healing rodent Achilles tendons.
      The addition of nitric oxide via nitric oxide-flurbiprofen enhanced rat Achilles
      tendon healing. The addition of nitric oxide to cultured human tendon cells via
      chemical means and via adenoviral transfection enhanced collagen synthesis,
      suggesting that one mechanism for the beneficial effect of nitric oxide on tendon
      healing might be via matrix synthesis. Most recently, 3 randomized, double-blind
      clinical trials evaluated the efficacy of nitric oxide donation via a patch in
      the management of the tendinopathy. In all 3 clinical trials, there was a
      significant positive beneficial effect of nitric oxide donation to the clinical
      symptoms and function of patients with Achilles tendinopathy, tennis elbow, and
      supraspinatus tendinitis.

PMID- 17509904
TI  - Three congenital variations in the long head of the biceps tendon: a review of
      pathoanatomic considerations and case reports.

PMID- 17509905
TI  - The complex characteristics of 282 unsatisfactory shoulder arthroplasties.
AB  - The purpose of our study is to augment the knowledge of patient dissatisfaction
      after a shoulder arthroplasty. A total of 353 shoulders were prospectively
      enrolled into the Shoulder Arthroplasty Failure Experience (SAFE) project. Of
      these, 282 patients had complete data for the final analysis, including
      demographic information, medical history, physical examination, standard
      radiographs, and the Simple Shoulder Test (SST) scores. These data were analyzed
      to determine the frequency of 17 possible characteristics of an unsatisfactory
      arthroplasty. Pain was the most common reason for patients to seek an evaluation
      (241 of 282 shoulders). Shoulder function was substantially reduced at
      presentation, with patients only able to perform an average of 2.6 of 12 SST
      functions. Overall, technical factors such as component malpositioning and
      glenohumeral malalignment were the most common characteristics identified among
      all the shoulders. Loosening of glenoid components was noted in 85 of the 136
      total shoulder arthroplasties, and glenoid erosion was found in 51 of 80
      hemiarthroplasties performed for degenerative conditions. Patients with an
      unsatisfactory outcome after shoulder arthroplasty present with poor shoulder
      function and pain. Component malposition, glenohumeral malalignment, and glenoid
      failure are all prevalent features among patients with an unsatisfactory outcome.

PMID- 17509906
TI  - Elimination of antigen-presenting cells and autoreactive T cells by Fas
      contributes to prevention of autoimmunity.
AB  - Fas (also known as Apo-1 and CD95) receptor has been suggested to control T cell
      expansion by triggering T cell-autonomous apoptosis. This paradigm is based on
      the extensive lymphoproliferation and systemic autoimmunity in mice and humans
      lacking Fas or its ligand. However, with systemic loss of Fas, it is unclear
      whether T cell-extrinsic mechanisms contribute to autoimmunity. We found that
      tissue-specific deletion of Fas in mouse antigen-presenting cells (APCs) was
      sufficient to cause systemic autoimmunity, implying that normally APCs are
      destroyed during immune responses via a Fas-mediated mechanism. Fas expression by
      APCs was increased by exposure to microbial stimuli. Analysis of mice with Fas
      loss restricted to T cells revealed that Fas indeed controls autoimmune T cells,
      but not T cells responding to strong antigenic stimulation. Thus, Fas-dependent
      elimination of APCs is a major regulatory mechanism curbing autoimmune responses
      and acts in concert with Fas-mediated regulation of chronically activated
      autoimmune T cells.

PMID- 17509907
TI  - Initiation of plasma-cell differentiation is independent of the transcription
      factor Blimp-1.
AB  - Blimp-1 is considered an essential regulator of the terminal differentiation of B
      cells into antibody-secreting plasma cells. We show here that Rag1-/- mice
      reconstituted with fetal liver cells homozygous for a DNA-binding-deficient
      mutant of Prdm1 (the gene encoding Blimp-1) lack a defined plasma-cell
      compartment, yet show detectable amounts of all immunoglobulin isotypes. In vitro
      analysis revealed that Blimp-1 is not required for the initiation of antibody
      secretion but is essential for subsequent high immunoglobulin production. Blimp-1
      independent differentiation was blocked at a preplasmablast stage characterized
      by decreased Pax5 expression and the activation of plasma-cell genes. Analysis of
      Blimp-1-sufficient differentiation revealed a phase prior to Blimp-1 expression
      in which several genes normally repressed by Pax5 are re-expressed, suggesting
      that plasma-cell differentiation is initiated by the inhibition of Pax5 function.
      Our results indicate that full plasma-cell differentiation but not commitment to
      the plasma-cell fate requires the expression of functional Blimp-1.

PMID- 17509908
TI  - Definition of germinal-center B cell migration in vivo reveals predominant
      intrazonal circulation patterns.
AB  - Proliferation, mutation, and selection in the germinal center (GC) are thought to
      occur in distinct microanatomical compartments-the dark zone (DZ) and the light
      zone (LZ). Thus, affinity maturation has been posited to require frequent
      trafficking between zones. Here we report the use of multiphoton in vivo
      microscopy to determine migration patterns of GC B cells. Analysis of time
      resolved images revealed unexpected patterns of movement as well as GC B cell
      morphology. Though frequent movement between the DZ and LZ was anticipated, few
      cells were observed to cross the interface between the two compartments.
      Moreover, cell-track trajectories indicated that cell movement in this region is
      predominantly parallel to the interface, suggesting that B cells circulate within
      individual LZ and DZ compartments. The results suggest a revision to our views of
      B cell circulation within GCs and the functional relationship of its two major
      compartments.

PMID- 17509909
TI  - Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory
      pathway.
AB  - The ability of natural-killer cells to regulate adaptive immunity is not well
      understood. Here we define an interaction between the class Ib major
      histocompatibility complex (MHC) molecule Qa-1-Qdm on activated T cells
      responsible for adaptive immunity and CD94-NKG2A inhibitory receptors expressed
      by natural-killer cells by using Qa-1-deficient and Qa-1 knockin mice containing
      a point mutation that selectively abolishes Qa-1-Qdm binding to CD94-NKG2A
      receptors. The Qa-1-NKG2A interaction protected activated CD4+ T cells from lysis
      by a subset of NKG2A+ NK cells and was essential for T cell expansion and
      development of immunologic memory. Antibody-dependent blockade of this Qa-1-NKG2A
      interaction resulted in potent NK-dependent elimination of activated autoreactive
      T cells and amelioration of experimental autoimmune encephalomyelitis. These
      findings extend the functional reach of the NK system to include regulation of
      adaptive T cell responses and suggest a new clinical strategy for elimination of
      antigen-activated T cells in the context of autoimmune disease and
      transplantation.

PMID- 17509910
TI  - Carotid sinus nerve blockade to reduce blood pressure instability following
      carotid endarterectomy: a systematic review and meta-analysis.
AB  - OBJECTIVES: Local anaesthetic infiltration into the carotid sinus during carotid
      endarterectomy (CEA) has been recommended to minimise blood pressure fluctuations
      but its use remains controversial. The aim of this meta-analysis was to determine
      whether intra-operative administration of local anaesthetic reduces the incidence
      of haemodynamic instability following CEA. MATERIALS AND METHODS: A search of the
      Medline, Pubmed and Embase databases and the Current Controlled Trials register
      identified four trials, which met the pre-defined inclusion criteria for data
      extraction. Pooled odds ratios with 95 per cent confidence intervals (c.i.) for
      the development of post-operative hypotension and hypertension were calculated
      using a random-effects model. RESULTS: Outcomes of 432 patients were studied.
      Local anaesthetic blockade of the carotid sinus was associated with a pooled odds
      ratio of 1.25 (95 per cent c.i. 0.496 to 3.15); p=0.216) and 1.28 (95 per cent
      c.i. 0.699 to 2.33; p=0.428) for the development of post-operative hypotension
      and hypertension respectively. Although none reach significance there was a trend
      towards increased risk of developing a complication in those patients who
      received local anaesthetic. CONCLUSIONS: There are insufficient data to determine
      the role of intra-operative local anaesthetic administration in reducing post
      operative blood pressure lability following CEA. Conversely, the possibility of
      harm cannot be excluded on the basis of the currently available data.

PMID- 17509911
TI  - Chordate ancestry of the neural crest: new insights from ascidians.
AB  - This article reviews new insights from ascidians on the ancestry of vertebrate
      neural crest (NC) cells. Ascidians have neural crest-like cells (NCLC), which
      migrate from the dorsal midline, express some of the typical NC markers, and
      develop into body pigment cells. These characters suggest that primordial NC
      cells were already present in the common ancestor of the vertebrates and
      urochordates, which have been recently inferred as sister groups. The primitive
      role of NCLC may have been in pigment cell dispersal and development. Later,
      additional functions may have appeared in the vertebrate lineage, resulting in
      the evolution of definitive NC cells.

PMID- 17509912
TI  - Non-hormonal cell types in the pituitary candidating for stem cell.
AB  - Hormone balances in the body are primarily governed by the hypothalamus-pituitary
      system. For its pivotal role, the pituitary gland relies on an assortment of
      different hormone-producing cell types, the proportions of which dynamically
      change in response to fluctuating endocrine demands. Mechanisms of pituitary
      cellular plasticity are at present far from understood, and may include
      proliferation and transdifferentiation of hormonal cells. Whether new cells also
      originate by recruitment from stem cells is unsettled, although this idea has
      frequently been proposed. Here, I will review these data by focusing on the non
      hormonal cell types that have been advanced as candidates for the pituitary stem
      cell position.

PMID- 17509913
TI  - Positioning the extreme anterior in Xenopus: cement gland, primary mouth and
      anterior pituitary.
AB  - The extreme anterior of the deuterostome embryo is unusual in that ectoderm and
      endoderm are directly juxtaposed, without intervening mesoderm. In all
      vertebrates, this region gives rise to the anterior pituitary, the primary mouth
      and, in most frogs, to the mucus-secreting cement gland. Using the frog Xenopus
      laevis as a paradigm, we suggest that, initially, the extreme anterior forms a
      homogenous domain characterized by expression of pitx genes. Subsequently, this
      domain becomes subdivided to form these three different structures under the
      influence of different inductive signals from surrounding tissues.

PMID- 17509914
TI  - Comparison of loline alkaloid gene clusters across fungal endophytes: predicting
      the co-regulatory sequence motifs and the evolutionary history.
AB  - LOL, a fungal secondary metabolite gene cluster found in Epichloe and
      Neotyphodium species, is responsible for production of insecticidal loline
      alkaloids. To analyze the genetic architecture and to predict the evolutionary
      history of LOL, we compared five clusters from four fungal species (single
      clusters from Epichloe festucae, Neotyphodium sp. PauTG-1, Neotyphodium
      coenophialum, and two clusters we previously characterized in Neotyphodium
      uncinatum). Using PhyloCon to compare putative lol gene promoter regions, we have
      identified four motifs conserved across the lol genes in all five clusters. Each
      motif has significant similarity to known fungal transcription factor binding
      sites in the TRANSFAC database. Conservation of these motifs is further support
      for the hypothesis that the lol genes are co-regulated. Interestingly, the
      history of asexual Neotyphodium spp. includes multiple interspecific
      hybridization events. Comparing clusters from three Neotyphodium species and E.
      festucae allowed us to determine which Epichloe ancestors are the most likely
      contributors of LOL in these asexual species. For example, while no present day
      Epichloe typhina isolates are known to produce lolines, our data support the
      hypothesis that the E. typhina ancestor(s) of three asexual endophyte species
      contained a LOL gene cluster. Thus, these data support a model of evolution in
      which the polymorphism in loline alkaloid production phenotypes among endophyte
      species is likely due to the loss of the trait over time.

PMID- 17509915
TI  - Signaling via the Trichoderma atroviride mitogen-activated protein kinase Tmk 1
      differentially affects mycoparasitism and plant protection.
AB  - Trichoderma atroviride is a mycoparasite of a number of plant pathogenic fungi
      thereby employing morphological changes and secretion of cell wall degrading
      enzymes and antibiotics. The function of the tmk 1 gene encoding a mitogen
      activated protein kinase (MAPK) during fungal growth, mycoparasitic interaction,
      and biocontrol was examined in T. atroviride. Deltatmk 1 mutants exhibited
      altered radial growth and conidiation, and displayed de-regulated infection
      structure formation in the absence of a host-derived signal. In confrontation
      assays, tmk 1 deletion caused reduced mycoparasitic activity although attachment
      to Rhizoctonia solani and Botrytis cinerea hyphae was comparable to the parental
      strain. Under chitinase-inducing conditions, nag 1 and ech 42 transcript levels
      and extracellular chitinase activities were elevated in a Deltatmk 1 mutant,
      whereas upon direct confrontation with R. solani or B. cinerea a host-specific
      regulation of ech 42 transcription was found and nag 1 gene transcription was no
      more inducible over an elevated basal level. Deltatmk 1 mutants exhibited higher
      antifungal activity caused by low molecular weight substances, which was
      reflected by an over-production of 6-pentyl-alpha-pyrone and peptaibol
      antibiotics. In biocontrol assays, a Deltatmk 1 mutant displayed a higher ability
      to protect bean plants against R. solani.

PMID- 17509916
TI  - An evaluation of the copper sequestrated during clotting in cattle: is it just
      caeruloplasmin?
AB  - In cattle, sequestration of copper (Cu) occurs during the clotting process so
      that serum Cu concentrations are markedly lower than plasma Cu. It has been
      suggested that all of the Cu lost during clotting is caeruloplasmin (CP). This
      study used paired samples from 125 cattle to assess whether this assumption was
      correct. The regression equations for plasma CP activity against plasma Cu
      concentration and serum CP against serum Cu had significantly different
      intercepts suggesting that at zero CP activity the amount of Cu remaining was
      dependent on sample type. Furthermore, the difference between serum and plasma Cu
      was unrelated to Cu status, whereas the difference between serum and plasma CP
      was related to Cu status. The regression equation for the loss of CP activity
      against change in Cu concentration had an intercept that was different from zero,
      indicating that a reduction in Cu concentration could occur even if CP activity
      was unaffected by clotting.

PMID- 17509917
TI  - Foot-and-mouth disease: a review of intranasal infection of cattle, sheep and
      pigs.
AB  - In an outbreak of foot-and-mouth disease (FMD) it is important to identify
      animals at risk from airborne virus. Investigations have been carried out over
      the years to determine the dose required to infect cattle, sheep and pigs by the
      intranasal route. This paper reviews the results of investigations for animals
      which have been infected by instillation or spraying a virus suspension into the
      nostrils or by exposure to affected animals through a mask or by indirect
      contact. The lowest doses were found by use of a mask. With virus from affected
      pigs given through a mask, doses of 18 infectious units (IU) in cattle and 8 IU
      in sheep were found to cause infection and give rise to lesions. Overall, cattle
      required the least amount of virus followed by sheep. Pigs required a dose of 22
      IU to cause infection and a dose of 125 IU to give rise to lesions. In many
      experiments pigs failed to become infected. With all three species the dose
      varied with the individual animal and the virus strain. For modelling previous
      outbreaks and in real time, a dose of 8 IU or 10 and 50% infectious doses (ID50)
      could be used where cattle and sheep were involved. Experience in the field,
      combined with the results from experiments involving natural infection, indicate
      that pigs are not readily infected by the intranasal route. However, for
      modelling purposes a dose of about 25 IU should be used with care. Investigations
      are needed to determine doses for virus strains currently in circulation around
      the world. In addition, the nature of the aerosol droplets needs to be analysed
      to determine how the respective amounts of infective and non-infective virus
      particles, host components and, in later emissions, the presence of antibody
      affect the survival in air and ability to infect the respiratory tract. Further
      work is also required to correlate laboratory and field findings through
      incorporation of the doses into modelling the virus concentration downwind in
      order that those responsible for controlling FMD are provided with the best
      available assessment of airborne spread. Finally, the doses found for infection
      by the intranasal route could be applied to other methods of spread where virus
      is inhaled to assess risk.

PMID- 17509918
TI  - Changes in haptoglobin, C-reactive protein and pig-MAP during a housing period
      following long distance transport in swine.
AB  - The aim of this study was to investigate the effects of a housing period
      following long distance transport on haptoglobin (Hp), C-reactive protein (CRP)
      and pig major acute phase protein (pig-MAP) in swine. After transportation, 80
      gilts were allotted to group A, B, C, or D. Blood samples were collected on
      arrival and 28 days later; additional samples were collected from Group C on day
      14, and from Group D on days 3, 5 and 14. Acute phase proteins (APPs) in Group A
      were significantly lower on day 28 than on day 1; the opposite occurred in Group
      B because of a tail biting episode. In Group C, values remained elevated on day
      14 and showed a reduction on day 28; in Group D elevated levels detected on day
      14 were preceded by a decrease from days 1 to 5. The results indicate that
      stressors associated with transportation and new accommodation can cause an
      increase in APPs that could be useful indicators of welfare during transport and
      routine management.

PMID- 17509919
TI  - Multi-dimensional gene target search for improving lycopene biosynthesis in
      Escherichia coli.
AB  - Identification of multiple gene targets that exhibit different modes of action
      toward a desired phenotype is a crucial step in strain improvement. Target
      identification methods based on traceable genetic perturbations and
      stoichiometric modeling have been employed before for the mining of putative
      overexpression and knock-out targets. Most search methods are sequential and, as
      such, quite limited in the space they can explore. In this study, we investigate
      a multi-dimensional search approach whereby unknown interactions of gene targets
      identified by different search methods are assessed by employing orthogonal
      search strategies. To this end, we combined knock-out and overexpression gene
      targets, identified through systematic and combinatorial approaches,
      respectively, in order to improve lycopene production in Escherichia coli.
      Specifically, we first identified multiple overexpression targets by screening
      genomic libraries of E. coli in a sequential-iterative manner. Targets so
      identified confirmed previously amplified genes in the non-mevalonate pathway
      (dxs and idi) and some regulatory genes (rpoS and appY). Additionally, this
      method revealed novel gene targets (yjiD, ycgW, yhbL, purDH, and yggT). A two
      dimensional search was subsequently undertaken, whereby the selected
      overexpression targets were combined with the knock-out targets predicted by
      stoichiometric modeling. All combinations of single (rpoS, appY, yjiD, ycgW, and
      yhbL), double (yjiD-ycgW) and triple (yjiD-ycgW-yhbL) overexpressions with four
      gene deletion backgrounds, including single (delta gdhA, or delta aceE), double
      (delta gdhA delta aceE), and triple (delta gdhA delta aceE delta fdhF) knockouts,
      were constructed and evaluated for lycopene production. Investigation of the
      metabolic landscape spanned by these 40 strains identified the best-engineered
      strain (T5(P)-dxs, T5(P)-idi, rrnB(P)-yjiD-ycgW, delta gdh delta aceE delta fdhF,
      pACLYC), which accumulated 16,000 ppm (16 mg/g cell) of lycopene within 24 h in a
      batch shake flask with 5 g/L of glucose in M9 minimal medium.

PMID- 17509920
TI  - A specific and potent inhibitor of glucosylceramide synthase for substrate
      inhibition therapy of Gaucher disease.
AB  - An approach to treating Gaucher disease is substrate inhibition therapy which
      seeks to abate the aberrant lysosomal accumulation of glucosylceramide. We have
      identified a novel inhibitor of glucosylceramide synthase (Genz-112638) and
      assessed its activity in a murine model of Gaucher disease (D409V/null).
      Biochemical characterization of Genz-112638 showed good potency (IC(50)
      approximately 24nM) and specificity against the target enzyme. Mice that received
      drug prior to significant accumulation of substrate (10 weeks of age) showed
      reduced levels of glucosylceramide and number of Gaucher cells in the spleen,
      lung and liver when compared to age-matched control animals. Treatment of older
      mice that already displayed significant amounts of tissue glucosylceramide (7
      months old) resulted in arrest of further accumulation of the substrate and
      appearance of additional Gaucher cells in affected organs. These data indicate
      that substrate inhibition therapy with Genz-112638 represents a viable alternate
      approach to enzyme therapy to treat the visceral pathology in Gaucher disease.

PMID- 17509921
TI  - Central nervous system aspergillosis in children: a systematic review of reported
      cases.
AB  - OBJECTIVE: Central nervous system (CNS) aspergillosis is a life-threatening
      disease that has had a published mortality of >80%. Little is known about this
      serious infection in the pediatric population. We conducted this study to analyze
      characteristics of CNS aspergillosis in infants and children. METHODS: The
      English literature was reviewed and all CNS aspergillosis cases in patients
      younger than 18 years of age were analyzed. RESULTS: Ninety cases were recorded
      up to June 2005. The median age of the patients was 9 years, ranging from 18 days
      to 18 years (15.6% younger than 1 year). CNS aspergillosis most commonly
      presented as brain abscess(es), either single or multiple. While prematurity was
      the predominant underlying condition among infants, leukemia was the most
      frequent underlying disease in children. Aspergillus fumigatus was isolated from
      75.5% of the cases. The overall mortality in published cases was 65.4%. In
      multivariate analysis, surgical treatment was independently associated with
      survival. CONCLUSION: CNS aspergillosis in infants and children predominantly
      presents as brain abscess(es) and has significantly better outcome compared to
      published adult data. The findings of this systematic review could assist future
      investigations for improved outcome of this life-threatening infection in
      pediatric patients.

PMID- 17509922
TI  - Enhancement of ultrasonically initiated emulsion polymerization rate using
      aliphatic alcohols as hydroxyl radical scavengers.
AB  - Ultrasonically initiated emulsion polymerization of styrene was carried out in
      the presence of aliphatic alcohols, e.g. methanol, ethanol, n-pronanol and n
      butanol, as volatile hydroxyl radical scavengers. With the addition of methanol,
      the polymerization rate of styrene increased, while the molecular weight and the
      average particle size of the produced polystyrene decreased because more radicals
      were produced in the presence of methanol. This is true also for the other
      polymerization system using other aliphatic alcohols, such as ethanol, n-pronanol
      and n-butanol, suggesting that the alcohols enter into cavitation bubbles and
      further react with hydroxyl radicals (*OH) from the sonolysis of water to produce
      hydroxyalkyl radicals, so as to reduce the recombination of *H and *OH radicals,
      therefore more radicals will be present in the systems for initiating
      polymerization. Obviously, it is an effective way to enhance ultrasonically
      initiated emulsion polymerization rate of styrene by adding volatile hydroxyl
      radical scavenger.

PMID- 17509923
TI  - Application of conformal transformation to elliptic geometry for electric
      impedance tomography.
AB  - Electrical impedance tomography (EIT) is a medical imaging modality that is used
      to compute the conductivity distribution through measurements on the cross
      section of a body part. An elliptic geometry model, which defines a more general
      frame, ensures more accurate results in reconstruction and assessment of
      inhomogeneities inside. This study provides a link between the analytical
      solutions defined in circular and elliptical geometries on the basis of the
      computation of conformal mapping. The results defined as voltage distributions
      for the homogeneous case in elliptic and circular geometries have been compared
      with those obtained by the use of conformal transformation between elliptical and
      well-known circular geometry. The study also includes the results of the finite
      element method (FEM) as another approach for more complex geometries for the
      comparison of performance in other complex scenarios for eccentric
      inhomogeneities. The study emphasizes that for the elliptic case the analytical
      solution with conformal transformation is a reliable and useful tool for
      developing insight into more complex forms including eccentric inhomogeneities.

PMID- 17509924
TI  - Visual impairment in Parkinson's disease treated with amantadine: case report and
      review of the literature.
AB  - A 61-year-old man with Parkinson's disease (PD) developed sudden-onset visual
      impairment after initiation of amantadine treatment. Ophthalmologic examination
      revealed corneal endothelial edema. Discontinuation of amantadine resulted in
      rapid improvement of visual acuity. A review of the literature indicated only a
      few reports of amantadine-associated corneal dysfunction in patients with
      neurological disorders as well as influenza syndrome, but none with PD.
      Amantadine-associated visual impairment in PD could be possibly overlooked, since
      PD mainly affects elderly people who often develop aging-related ocular changes.
      The present report alerts neurologists and physicians in general to the peculiar
      ophthalmologic side effect of amantadine.

PMID- 17509925
TI  - Lipid metabolism and diet: possible mechanisms of slow aging.
AB  - The ability to survive to an extremely old age is a consequence of complex
      interactions among genes, environment, lifestyle and luck. In the last two
      centuries, life expectancy in western countries has doubled, increasing from 40
      to 81 years (79 for males and 82 for females). The candidate factors to determine
      such mortality reduction are reduced exposure to infections and the subsequent
      reduction in inflammatory responses, and to some extent, improvement in diet and
      nutrition. Among the people born at the beginning of the previous century, a
      small portion of individuals (1 in 10,000 born) have reached 100 years, surviving
      approximately 20 years more than the general population. The successful longevity
      of these individuals shows a familial component, possibly genetic, as underlined
      by the centenarian sibling's increased chance of reaching 100 years of age
      compared to the general population. Genetic studies on long living individuals
      have led to the discovery of potential genetic causes of extreme longevity. These
      discoveries have highlighted the role of lipid metabolism as a potential key
      player in the ability to survive to extreme old age. Additional studies on the
      longevity phenotype have confirmed the role of lipids and lipid-associated cell
      activities in the predisposition to longevity, from lower eukaryotes to humans.
      The main focus of this review is the appreciation of demographic survival data
      and changes in recent diet with the above mentioned genetic and phenotypic
      biomarkers of longevity, in order to elucidate hypotheses on mechanisms of slow
      aging and disease resistance.

PMID- 17509926
TI  - Interleukin-21: a new modulator of immunity, infection, and cancer.
AB  - Interleukin-21 is the most recently discovered member of the type-I cytokine
      family. Structurally, IL-21 shows homology to IL-2, IL-4, and IL-15 proteins. IL
      21 shares the common gamma-chain with the other three cytokines but, in addition,
      binds to a unique IL-21Ralpha chain, and activates the JAK/STAT pathway. IL-21 is
      mainly produced by activated T-cells but targets a broad range of lymphoid and
      myeloid cells of the immune system and therefore is able to regulate innate and
      acquired immune responses. This review intends to give the reader an overview of
      the recent findings concerning the biology of IL-21 and its physiological role in
      immunity, infection, and cancer.

PMID- 17509927
TI  - A robotic indenter for minimally invasive measurement and characterization of
      soft tissue response.
AB  - The lack of experimental data in current literature on material properties of
      soft tissues in living condition has been a significant obstacle in the
      development of realistic soft tissue models for virtual reality based surgical
      simulators used in medical training. A robotic indenter was developed for
      minimally invasive measurement of soft tissue properties in abdominal region
      during a laparoscopic surgery. Using the robotic indenter, force versus
      displacement and force versus time responses of pig liver under static and
      dynamic loading conditions were successfully measured to characterize its
      material properties in three consecutive steps. First, the effective elastic
      modulus of pig liver was estimated as 10-15 kPa from the force versus
      displacement data of static indentations based on the small deformation
      assumption. Then, the stress relaxation function, relating the variation of
      stress with respect to time, was determined from the force versus time response
      data via curve fitting. Finally, an inverse finite element solution was developed
      using ANSYS finite element package to estimate the optimum values of viscoelastic
      and nonlinear hyperelastic material properties of pig liver through iterations.
      The initial estimates of the material properties for the iterations were
      extracted from the experimental data for faster convergence of the solutions.

PMID- 17509928
TI  - Tunneling descent for m.a.p. active contours in ultrasound segmentation.
AB  - Active contours that evolve in ultrasound images under gradient descent are often
      trapped in spurious local minima. This paper presents an evolution strategy
      called tunneling descent, which is capable of escaping from such minima. The key
      idea is to evolve the contour by a sequence of constrained minimizations that
      move the contour in to, and out of, local minima. This strategy is an extension
      of classical gradient descent. Because tunneling descent does not terminate at a
      local minima an explicit stopping rule is required. Model-based and model-free
      stopping rules are presented and formulae for choosing the stopping threshold are
      given. The algorithm is used to segment the endocardium in 44 short axis cardiac
      ultrasound images. The energy function of the active contour is derived from a
      m.a.p. formulation. All segmentations are achieved without tweaking either the
      energy function or numerical parameters. Experimental evaluation of the
      segmentations show that the algorithm overcomes multiple local minima to find the
      endocardium. The accuracy of the algorithm is comparable to that of manual
      segmentations and significantly better than classical gradient descent active
      contours. The sensitivity of the segmentation to initialization is also evaluated
      and it is shown that segmentations from quite different initializations are close
      to each other. Finally, some limitations of the m.a.p. formulation are discussed.

PMID- 17509929
TI  - Genotoxic and mutagenic effects of diesel oil water soluble fraction on a
      neotropical fish species.
AB  - Numerous spills and leakages involving petroleum and its derivatives have
      recently occurred in Brazilian rivers. Considering the lack of information
      regarding the genotoxic response of neotropical fish to these events and the
      predominance of information regarding saltwater fish, which offers no genuine
      comparisons, the present work aimed to evaluate the genotoxicity and mutagenicity
      of the diesel water soluble fraction (DWSF) on the neotropical fish Prochilodus
      lineatus under acute (6, 24 and 96h) and subchronic (15 days) exposures, using
      the comet (SCGE) and micronucleus assays. The results indicated genotoxic and
      mutagenic damage in erythrocytes of P. lineatus exposed to DWSF. Comet scores for
      fish exposed to DWSF in all experimental periods were significantly higher than
      the respective negative control groups (fish exposed to clean water for the same
      period). The relative frequencies of micronucleated erythrocytes for P. lineatus
      exposed to DWSF under acute and subchronic treatment were also significantly
      higher than their respective negative controls. Taken together these results
      showed that acute and subchronic exposures to DWSF produce mutagenic and
      genotoxic effects on the blood cells of P. lineatus and that the combination of
      comet and micronucleus assays proved to be both suitable and useful in the
      evaluation of the genotoxicity of diesel oil due to their complementary action.

PMID- 17509930
TI  - Improved alkaline comet assay protocol for adherent HaCaT keratinocytes to study
      UVA-induced DNA damage.
AB  - The comet assay is one of the well-accepted tests to measure radiation-induced
      DNA damage. The most commonly used protocols require single-cell suspensions that
      are embedded in agarose in order to perform electrophoresis. For adherently
      growing cells such as human HaCaT skin keratinocytes this method bears several
      problems. We show that trypsinization required for maintaining single-cell
      suspensions is prolonged after UV radiation and thereby reduces cell viability
      and allows partial repair, with the consequence of reduced damage detection after
      irradiation. Therefore, we here introduce a modified version of the comet assay
      where HaCaT cells are seeded onto comet slides 24h before the assay and overlaid
      with agarose immediately after irradiation. Using this modification we are now
      able to reproducibly measure high DNA-damage levels (13-fold increase compared
      with controls) following irradiation with 60J/cm(2) UVA as well as a dose
      dependent increase of DNA damage after 10, 20 and 60J/cm(2) UVA. Thus, by
      maintaining the cells in their natural configuration, i.e. adherently growing, we
      exclude several artefacts that are likely to influence the damage responses.
      These include: (i) trypsinization-dependent changes in cell morphology and
      polarity (clear lateral, i.e. adherent, and apical side of keratinocytes) which
      are likely of consequence for the gene-expression pattern, (ii) trypsin- and
      dislodgement-induced damage reducing cell viability, and (iii) the time delay
      between damage induction and damage evaluation to unpredictable results due to
      partial repair. Since these advantages pertain to all adherently growing cells,
      this improved protocol is not restricted to HaCaT cells but offers great
      potential also with all non-haematopoietic cells for obtaining accurate results
      and for studying repair processes in a highly reproducible manner.

PMID- 17509931
TI  - Features of the alkynyl ruthenium chromophore with modified anionic subsystem UV
      absorption.
AB  - Theoretical simulation of UV-vis absorption for a new series of alkynyl ruthenium
      chromophores spectra and investigations the influence of anionic substituence on
      a spectral shift of UV absorption was presented. The MM(+) molecular force field
      method was used for total energy minimization and for building of the molecular
      optimized geometry [S.J. Weiner, P.A. Kollman, D.A. Case, U.C. Ghio, G. Alagona,
      J.S. Profeta, P. Weiner, J. Am. Chem. Soc. 106 (1984) 765; S.J. Weiner, P.A.
      Kollman, D.T. Nguyen, D.A. Case, J. Comput. Chem. 7 (1986) 230]. All quantum
      chemical calculations were performed by semi-empirical ZINDO/1 method within a
      framework of the restricted Hartree-Fock approach and convergence limit up to 10(
      6)eV after 500 iterations was achieved. Good agreement between the theoretically
      calculated and experimentally measured spectra was observed. The largest spectral
      shift in position of absorption peaks was observed for compound containing the
      anionic (Cl), substituent. The theoretically calculated absorption maximum is
      blue shifted with respect to the experimental spectra for all compounds what is
      connected with the changes of the charge transfer determining the corresponding
      state dipole moments. Analysis of the theoretical spectra shows a substantial
      sensitivity to the backside groups.

PMID- 17509932
TI  - Investigation of optical nonlinearities of an azo dye using a 532nm diode-pumped
      Nd:YAG laser.
AB  - Solid-state dye-doped polymers are attractive alternatives to the conventional
      liquid dye systems. In this paper, the third order nonlinear optical property of
      Sudan III, an azo dye in solvents and dye doped polymer films measured using the
      Z-scan technique is reported. Multiple diffraction rings were observed when the
      dye doped in both the liquid and solid media was exposed to a diode-pumped Nd:YAG
      laser at 532nm.

PMID- 17509933
TI  - Spectroscopic and theoretical study on the interaction between diperoxovanadate
      and oxazole.
AB  - Detailed investigations were carried out to explore the interaction systems of
      NH(4)VO(3)/H(2)O(2)/oxazole in aqueous solution under physiological conditions by
      a combined use of multinuclear NMR ((1)H, (13)C, (14)N and (51)V), diffusion
      ordered spectroscopy (DOSY), variable temperature NMR, electrospray ionization
      mass spectrometry (ESI-MS), spin-lattice relaxation and density functional
      calculations. The results indicated the formation of a new peroxovanadate species
      [OV(O(2))(2)(oxazole)](-) with oxazole coordinating to vanadium through nitrogen
      atom. The solution structure of the new species was predicted from theoretical
      calculations.

PMID- 17509934
TI  - Sensitivity and specificity of three ELISA-based assays for discriminating
      primary from secondary acute dengue virus infection.
AB  - BACKGROUND: Discrimination between primary and secondary dengue virus infection
      traditionally has been performed using the hemagglutination inhibition (HI) test.
      However, this test has practical limitations and disadvantages. OBJECTIVE: To
      evaluate the ability of three ELISA-based methods (IgG avidity test, IgM/IgG
      ratio and IgG titer) to discriminate primary from secondary dengue infection.
      STUDY DESIGN: Serum samples from convalescent-phase patients with confirmed
      acute, primary (n=46) or secondary (n=33) dengue virus infection were tested
      using three ELISA-based methods. A ROC curve was employed to establish the cut
      off points and to evaluate the ability of the three methods to distinguish
      between acute, primary and secondary dengue virus infection. RESULTS: All three
      assays exhibited sensitivity and negative predictive values of 100% for defining
      secondary infection. The specificity and positive predictive values were
      respectively 97.8% and 93.7% for the IgG avidity test, 95.7% and 88.2% for the
      IgM/IgG ratio assays, and 97.8% and 93.7% for the IgG titer assay. CONCLUSION:
      All three ELISA-based assays proved reliable tools for discriminating between
      acute, primary and secondary dengue virus infection when using serum samples from
      convalescent-phase patients.

PMID- 17509935
TI  - Vaccine-associated paralytic poliomyelitis in a patient with MHC class II
      deficiency.
AB  - Vaccine-associated paralytic poliomyelitis (VAPP) is a rare complication of oral
      polio vaccine. We describe a fatal case of VAPP in an 8-month-old boy with Major
      Histocompatibility Class II deficiency. The isolated poliovirus was a Sabin type
      2-type 1 recombinant that showed 1.4% VP1 divergence from Sabin type 2.

PMID- 17509936
TI  - Development and gender in the P50 paradigm.
AB  - OBJECTIVE: The relative change in amplitude of the P50 component in response to
      the second click compared to the first one is commonly thought to index sensory
      gating. Despite numerous P50 gating studies, reports about its development are
      scarce. The present study examined the development and gender differences of P50
      sensory gating. METHODS: A standard P50 paradigm was used to study sensory gating
      in adults (N=31) and in children aged 10-12 years (N=29), 8-9 years (N=26) and 5
      7 years (N=26). RESULTS: The speed of processing and the frontocentral scalp
      distribution in P50 sensory gating are already mature at the age of 5 years.
      However, children of 5-7 years of age had smaller amplitudes to the first
      response and showed less sensory gating compared to the older age groups. No
      gender differences were found. CONCLUSIONS: Sensory gating matures around the age
      of 8 years. SIGNIFICANCE: The current data help in evaluating whether abnormal
      P50 sensory gating is due to maturational delay. There is no need to take into
      account gender differences.

PMID- 17509937
TI  - Neural logic molecular, counter-intuitive.
AB  - A hypothesis is proposed that multiple "LOGIC" genes control Boolean logic in a
      neuron. Each hypothetical LOGIC gene encodes a transcription factor that
      regulates another LOGIC gene(s). Through transcription regulation, LOGIC genes
      connect into a complex circuit, such as a XOR logic gate or a two-input flip-flop
      logic circuit capable of retaining information. LOGIC gene duplication, mutation
      and recombination may result in the diversification of Boolean logic gates.
      Creative thinking may sometimes require counter-intuitive reasoning, rather than
      common sense. Such reasoning is likely to engage novel logic circuits produced by
      LOGIC somatic mutations. An individual's logic maturates by a mechanism of
      somatic hypermutation, gene conversion and recombination of LOGIC genes in
      precursor cells followed by selection of neurons in the brain for functional
      competence. In this model, a single neuron among billions in the brain may
      contain a unique logic circuit being the key to a hard intellectual problem. The
      output of a logic neuron is likely to be a neurotransmitter. This neuron is
      connected to other neurons in the spiking neural network. The LOGIC gene
      hypothesis is testable by molecular techniques. Understanding mechanisms of
      authentic human ingenuity may help to invent digital systems capable of creative
      thinking.

PMID- 17509938
TI  - Women's interpretation of cardiac symptoms at the time of their cardiac event:
      the effect of co-occurring illness.
AB  - BACKGROUND: Women tend to access medical help for a myocardial infarction later
      than men and are at a disproportionate risk of dying or of suffering disability
      as a consequence. Co-morbidity is associated with delay but little is known how
      this affects decision making. AIM: To examine the effect of co-occurring chronic
      illness or infections on women's interpretation of their symptoms and action at
      the time of their cardiac event. METHODS: Semi-structured interviews with 44
      women admitted to 3 district hospitals following a cardiac event. For the
      purposes of analysis they were divided into those who arrived at the hospital
      within 12 h of onset of symptoms (<12 hour group) and those who took more than 12
      h (>12 hour group). FINDINGS: Women utilised their mental records of knowledge
      and experiences to make sense of their cardiac symptoms. The mental records of
      the <12 hour group contained knowledge of symptoms and previous experiences
      relevant to cardiac problems. Those of the >12 hour group contained knowledge and
      experience of recent and co-occurring chronic illnesses, this provided persuasive
      'evidence' to suggest that their symptoms were normal or typical for their
      current state of health and resulted in delay. CONCLUSION: Women's decision
      making and timely access to medical help at the time of a cardiac event is
      influenced by their repertoire of knowledge and experience. Interventions need to
      be designed to capture the process of symptom recognition and the influence of co
      morbidity.

PMID- 17509939
TI  - Neuromuscular control of the head in an isometric force reproduction task:
      comparison of whiplash subjects and healthy controls.
AB  - BACKGROUND CONTEXT: A number of recent scientific publications suggest that
      patients suffering from whiplash-associated disorders (WADs) exhibit sensorimotor
      deficits in the control of head and neck movements. PURPOSE: The main objective
      of the present study was to evaluate if subjects with WADs can produce isometric
      neck extension and flexion forces with precision, variability, and a mode of
      control similar to the values of healthy subjects. STUDY DESIGN: A control group
      study with repeated measures. PATIENT SAMPLES: Neck force production parameters
      and neuromuscular control were measured in 17 whiplash and 14 control subjects.
      The experimental group included subjects who had a history of persistent neck
      pain or disability after a motor vehicle accident. OUTCOME MEASURES: Pain levels
      were assessed on a standard 100-mm visual analog pain scale at the beginning and
      end of the experiment. Each whiplash subject completed the neck disability index
      and the short-form 36 health survey (SF-36) questionnaire before the experiment.
      METHODS: All subjects were asked to exert flexion and extension forces against a
      fixed head harness. Kinetic variables included time to peak force, time to peak
      force variability, peak force variability, and absolute error in peak force.
      Surface electrodes were applied bilaterally over the sternocleidomastoideus and
      paraspinal muscles. Electromyography (EMG)-dependent variables included EMG burst
      duration and amplitude using numerical integrated techniques. RESULTS: The
      average time to peak force was significantly longer for whiplash subjects than
      for the healthy controls. A significant increase in peak force variability was
      also observed in the whiplash group, and no group differences were noted for
      absolute error. Heightened muscular activity was seen in both paraspinal muscles,
      even though it only reached statistical significance for the left paraspinal
      muscle. CONCLUSION: Our results show that the whiplash subjects involved in the
      study were able to produce isometric forces with spatial precision similar to
      healthy controls using a motor strategy in which the time to peak force is
      increased. This trade-off between spatial precision and time to peak force
      probably reflects an adaptation aimed at limiting pain and further injuries.

PMID- 17509940
TI  - Muscular and brain cholinesterase sensitivities to azinphos methyl and carbaryl
      in the juvenile rainbow trout Oncorhynchus mykiss.
AB  - The organophosphate azinphos methyl (AzMe) and the carbamate carbaryl are the
      insecticides mostly used in the irrigated valley of Rio Negro and Neuquen,
      Patagonia, Argentina. Juvenile rainbow trout were exposed to AzMe and carbaryl
      and the sensitivity of skeletal muscular cholinesterase (ChE) and the time course
      of inhibition and recovery were evaluated. EC50 values demonstrated that AzMe was
      a stronger in vivo inhibitor of muscular ChE (1.05+/-0.23 microg/L) than carbaryl
      (270+/-62.23 microg/L). Muscular ChE was significantly less sensitive to both
      insecticides than brain ChE. EC50 values obtained for muscular ChE were closer
      than those for brain ChE to the respective pesticide lethal concentrations,
      pointing out the relevance of the muscular enzyme in determining acute toxicity.
      The recovery process of ChE activity after carbaryl exposure (500 microg/L) was
      fast, whereas no significant recovery was observed with AzMe (1 microg/L) after
      21 days in uncontaminated media. Brain and muscular ChE were inhibited and showed
      a significant but not complete recovery after three consecutive 48-h exposures to
      AzMe (1 microg/L) followed by a recovery period of 7 days. This scheme mimics the
      periodical application of the insecticides in the region and suggests a certain
      probability of a sustained ChE inhibition under field conditions, affecting fish
      development and survival.

PMID- 17509941
TI  - The effects of anticoagulants on hematological indices and blood cell morphology
      of common carp (Cyprinus carpio L.).
AB  - Hematological parameters (Ht, Hb, RBC, WBC, PLT), erythrocyte size, and osmotic
      fragility, differential leukocyte count, ROS production in common carp blood
      collected on three anticoagulants: heparin (10 IU/mL, Na2EDTA (0.1, 0.5, and 1
      mg/mL), and sodium citrate (0.3 mg/mL) were compared. Na2EDTA caused partial
      blood hemolysis in Ht tubes which made Ht measurement impossible, and resulted in
      high variability of the results. Both, citrate and Na2EDTA increased sensitivity
      of red blood cells to hemolysis. Na2EDTA also induced erythrocyte anisocytosis
      and anisonucleosis. Na2EDTA significantly increased ROS production but no effect
      of anticoagulants on WBC, PLT or differential leukocyte count was observed. The
      obtained results show that Na2EDTA should not be used for evaluation of red blood
      cell parameters and erythrocyte morphology, and for ROS production measurement in
      common carp. Heparin proved to be the most appropriate anticoagulant to use for
      this species, although Na2EDTA and sodium citrate may be used for WBC and
      leukocyte differential count evaluations.

PMID- 17509942
TI  - Unsupervised clustering of over-the-counter healthcare products into product
      categories.
AB  - A general problem in biosurveillance is finding appropriate aggregates of
      elemental data to monitor for the detection of disease outbreaks. We developed an
      unsupervised clustering algorithm for aggregating over-the-counter healthcare
      (OTC) products into categories. This algorithm employs MCMC over hundreds of
      parameters in a Bayesian model to place products into clusters. Despite the high
      dimensionality, it still performs fast on hundreds of time series. The procedure
      was able to uncover a clinically significant distinction between OTC products
      intended for the treatment of allergy and OTC products intended for the treatment
      of cough, cold, and influenza symptoms.

PMID- 17509943
TI  - Analysis of keratin polypeptides 8 and 19 variants in inflammatory bowel disease.
AB  - BACKGROUND/AIMS: Keratin-8 (KRT8)-null mice develop spontaneous colitis and
      predisposition to liver injury. Human studies show that some KRT8 variants
      predispose to end-stage liver disease and progression and suggest that such
      variants might associate with UC or CD. We asked whether mutations in KRT8 or
      KRT19, the major intestinal keratins, are associated with UC/CD. METHODS: Exonic
      regions of the KRT8/KRT19 genes were polymerase chain reaction-amplified using
      genomic DNA from 2 independent groups. Group I included 91 unrelated patients
      with CD, 93 unrelated patients with UC, and 70 unrelated/unaffected volunteers.
      KRT8 variants were also tested with pyrosequencing in Group II that included 682
      independent nuclear families with both parents and at least 1 CD/UC-affected
      offspring and 273 unaffected controls. Both cohorts were enriched for familial
      IBD. RESULTS: In Group I, KRT19 variants were identified in CD/UC patients within
      the promoter and exons 1+2, with similar mutation frequencies in the
      control/CD/UC groups. In contrast, 16 of 184 CD+UC patients harbored KRT8
      heterozygous variants involving Gly62-to-Cys and Arg341-to-His and a novel Arg341
      to-Cys, which were noted in 4 volunteers (Arg341-to-His) and correlated with
      extensive UC (P = .005). One family with unaffected parents had 3 pediatric
      affected siblings with severe disease, 2 of whom are compound heterozygous (Gly62
      to-Cys/Arg341-to-His). However, there was no significant departure from random
      transmission of the 3 alleles in Group II IBD families. CONCLUSIONS: KRT8 and
      KRT19 variants are not overtransmitted or associated with familial IBD, although
      a potential role in sporadic IBD cannot be excluded. A novel but rare keratin-8
      Arg341-to-Cys is identified in IBD patients.

PMID- 17509944
TI  - Hepatotoxicity associated with dietary supplements containing anabolic steroids.
AB  - BACKGROUND & AIMS: The aim of this article was to re-emphasize the hepatotoxicity
      associated with the use of anabolic androgenic steroids and to highlight the
      marketing and sale of anabolic androgenic steroids as dietary supplements.
      METHODS: This was a case series of 2 patients who developed a cholestatic liver
      panel after consumption of anabolic androgenic steroids. A detailed
      Pubmed/Medline search was performed to research this topic. RESULTS: We present 2
      young men who developed significant cholestatic liver injury after consumption of
      anabolic androgenic steroids. This was associated with considerable morbidity,
      although both patients recovered without the need for a liver transplant. Both of
      these anabolic androgenic steroids were being marketed as dietary supplements.
      CONCLUSIONS: Despite being classified as class III controlled substances,
      anabolic androgenic steroids are still a cause for serious hepatotoxicity in the
      United States. Some of these anabolic androgenic steroids are being marketed as
      dietary supplements. Although the Food and Drug Administration is making
      concerted efforts to regulate this, increased vigilance also is required from the
      medical profession.

PMID- 17509945
TI  - Mycophenolate mofetil in autoimmune hepatitis patients not responsive or
      intolerant to standard immunosuppressive therapy.
AB  - BACKGROUND & AIMS: The immunosuppressive treatment for autoimmune hepatitis (AIH)
      patients is prednisone and azathioprine. Ten percent to 20% of patients do not
      respond or are intolerant of standard treatment. The aim of this study was to
      assess the biochemical, histologic, and hematologic parameters during
      mycophenolate mofetil (MMF) treatment in AIH patients who did not respond to or
      were intolerant of prednisone and/or azathioprine. METHODS: A retrospective study
      was performed of 15 AIH patients who received MMF either as monotherapy or in
      combination with prednisone after failure or intolerance of the initial regimen.
      Records were reviewed as to initial therapy, reasons why MMF was initiated, liver
      enzyme levels, histology on MMF, and complications. RESULTS: The mean age was 60
      +/- 15 years. All patients were started on MMF at 1 gram twice a day, 3 on MMF
      monotherapy, and 12 on prednisone and MMF. The average MMF treatment duration was
      41 months. Alanine aminotransferase levels decreased significantly from 91.73 +/-
      88.69 to 60.87 +/- 71.2 (P = .03) on MMF treatment. Inflammatory scores (2.59 +/-
      0.97 to 1.14 +/- 1.21, P = .02) and Ishak fibrosis scores (4.10 +/- 1.37 to 2.5
      +/- 1.51, P = .02) also decreased. No significant hematologic complications were
      noted during MMF treatment. CONCLUSIONS: Administration of MMF, either as
      monotherapy or in combination with prednisone, results in biochemical and
      histologic improvement in AIH patients who are prednisone and/or azathioprine
      intolerant or resistant without the development of significant complications. MMF
      should be studied prospectively as an alternative agent in the treatment of
      autoimmune liver disease.

PMID- 17509946
TI  - Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis.
AB  - BACKGROUND & AIMS: Independent predictors of hepatocellular carcinoma in patients
      with cirrhosis are not well established. METHODS: We created a cohort of 2126
      patients (41% with hepatitis C virus [HCV] infection) who sought care from all
      Veterans Affairs health care centers in the northwest United States from 1994 to
      2005 and who had a diagnosis of cirrhosis recorded in inpatient or outpatient
      medical records. RESULTS: During a mean follow-up period of 3.6 years, 100
      patients were diagnosed with hepatocellular carcinoma (incidence, 1.3 per 100
      patient-years). Important predictors of hepatocellular carcinoma in multivariate
      models included HCV infection (adjusted hazard ratio [ahr], 3.0; 95% confidence
      interval [CI], 1.7-5.3); hepatitis B virus (HBV) surface antigen (ahr, 3.3; 95%
      CI, 1.4-7.7); HBV core antibody (ahr, 1.7; 95% CI, 1.1-2.8); obesity (ahr, 2.5;
      95% CI, 1.3-4.9), and overweight (ahr, 2.8; 95% CI, 1.5-5.4) relative to patients
      with a body mass index of < 25 kg/m2, diabetes (ahr, 1.5; 95% CI, 0.9-2.5), and
      low platelet count (relative to patients with a platelet count of > 266
      thousands/microL, the ahr was 2.1 [95% CI, 0.8-5.6] in patients with a platelet
      count of 180-266 thousands/microL, 3.3 [95% CI, 1.3-8.0] in patients with a
      platelet count of 111-179 thousands/microL, and the ahr was 4.7 [95% CI, 2.0
      11.4] in patients with a platelet count of < or = 110 thousands/microL).
      CONCLUSIONS: We identified 6 important predictors of hepatocellular carcinoma in
      multivariate models (including relatively novel predictors such as increased body
      mass index, HBV core antibody, and low platelet count), which suggest a means of
      predicting the risk of hepatocellular carcinoma in patients with cirrhosis and
      optimizing surveillance strategies.

PMID- 17509947
TI  - Diagnostic criteria and adjudication process both determine published event
      rates: the ACTION trial experience.
AB  - OBJECTIVE: Few trials report event-adjudication procedures in detail. Using data
      from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine
      GITS) study, we compared the impact on event-rates of an adjudication strategy
      based on systematic screening of all reported serious adverse events (SAEs) with
      a strategy based on investigator diagnoses. The final diagnosis was always made
      by a critical events committee (CEC) using standard criteria. METHODS: ACTION
      randomized 7665 patients with stable angina to either nifedipine or placebo. Pre
      specified events included acute or procedural myocardial infarction (MI),
      refractory angina, heart failure and debilitating stroke. Clinically related SAEs
      including in-hospital procedures were combined into episodes independent from the
      investigator diagnoses entered on SAE reports. All fatal episodes and those
      episodes suggestive of pre-specified events were adjudicated by the CEC. RESULTS:
      During follow-up, 17,081 episodes were reported in 5312 patients. The SAE
      descriptions ruled out the occurrence of a pre-specified event in 28%. The
      remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory
      angina, 275 of heart failure and 190 of debilitating stroke were diagnosed
      (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397
      patients) that were fatal or for which the investigator had reported any of the
      diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure
      and 14 of debilitating stroke would have been missed (total=228). CONCLUSION:
      Both the diagnostic criteria used and the adjudication process determine event
      rates and conclusions about treatment effects in clinical trials. Published trial
      reports should always state if event-adjudication was independent of the
      diagnoses of investigators, and if all events of interest were adjudicated or
      only the first one.

PMID- 17509948
TI  - Feasibility study for cell electroporation detection and separation by means of
      dielectrophoresis.
AB  - Electroporation is a phenomenon during which exposure of a cell to high voltage
      electric pulses results in a significant increase in its membrane permeability.
      Aside from the fact that after the electroporation the cell membrane becomes more
      permeable, the cells' geometrical and electrical properties change considerably.
      These changes enable use of the force on dielectric particles exposed to non
      uniform electric field (dielectrophoresis) for separation of non-electroporated
      and electroporated cells. This paper reports the results of an attempt to
      separate non-electroporated and electroporated cells by means of
      dielectrophoresis. In several experiments we managed to separate the non
      electroporated and electroporated cells suspended in a medium with conductivity
      0.174 S/m by exposing them to a non-uniform electric field at a frequency of 2
      MHz. The behaviour of electroporated cells exposed to dielectrophoresis raises
      the presumption that in addition to conductivity, considerable changes in
      membrane permittivity occur after the electroporation.

PMID- 17509949
TI  - ND4 mutation in transitional cell carcinoma: Does mitochondrial mutation occur
      before tumorigenesis?
AB  - To investigate how mitochondrial mutation occurs in cancers, we analyzed ND4
      mutation in 53 transitional cell carcinomas (TCCs) of the upper urinary tract and
      the normal counterpart (perirenal soft tissue). Three methods, i.e., DNA
      sequencing, restriction fragment length polymorphism (RFLP), and denaturing high
      performance liquid chromatography (DHPLC), were employed because of their
      different sensitive of detecting mutation. The results of sequencing and RFLP
      showed that ND4 mutations were only found in 24.5% (13/53) of tumor. However, 11
      of these mutations could also be identified in the normal tissue by DHPLC,
      indicating that most mitochondrial mutations identified in tumors preexist as
      minor components, which are too low in quantity to be detected by less sensitive
      methods such as DNA sequencing. The result suggests that mtDNA mutation occurs
      before tumorigenesis and become apparent in cancer cells.

PMID- 17509951
TI  - Determination of atomoxetine in human plasma by a high performance liquid
      chromatographic method with ultraviolet detection using liquid-liquid extraction.
AB  - A HPLC method with UV detection (210 nm) was developed and validated for the
      quantification of atomoxetine, a new medication for the treatment of attention
      deficit/hyperactivity disorder, in human plasma. Following a two-step liquid
      liquid extraction with diethyl ether, the analyte and internal standard
      (maprotiline) were separated using an isocratic mobile phase of
      acetonitrile/phosphate buffer (39/61, v/v, pH 6.6) on a reverse phase Inertsil
      C(18) column. Linearity was verified over the range of 3.12-200 ng/mL atomoxetine
      in plasma. The lowest limit of detection is 2.5 ng/mL (S/N=10). This HPLC method
      was validated with within- and between-batch precisions of 4.9-14.4% and 4.7
      13.1%, respectively. The within- and between-batch biases were -1.9 to 1.4% and
      0.1-13.8%, respectively. Commonly used psychotropic drugs and frequently
      coadministered drugs did not interfere with the drug and internal standard. This
      method is simple, economical and specific, and has been used successfully in a
      pharmacokinetic study of atomoxetine.

PMID- 17509950
TI  - Influence of XPB helicase on recruitment and redistribution of nucleotide
      excision repair proteins at sites of UV-induced DNA damage.
AB  - The XPB DNA helicase, a subunit of the basal transcription factor TFIIH, is also
      involved in nucleotide excision repair (NER). We examined recruitment of NER
      proteins in XP-B cells from patients with mild or severe xeroderma pigmentosum
      (XP) having different XPB mutations using local UV-irradiation through filters
      with 5 microm pores combined with fluorescent antibody labeling. XPC was rapidly
      recruited to UV damage sites containing DNA photoproducts (cyclobutane pyrimidine
      dimers, CPD) in all the XP-B and normal cells, thus reflecting its role in damage
      recognition prior to the function of XPB. Cells from the mild XP-B patients, with
      a missense mutation, showed delayed recruitment of all NER proteins except XPC to
      UV damage sites, demonstrating that this mutation impaired localization of these
      proteins. Surprisingly, in cells from severely affected patients, with a C
      terminal XPB mutation, XPG and XPA proteins were normally recruited to UV damage
      sites demonstrating that this mutation permits recruitment of XPG and XPA. In
      marked contrast, in all the XP-B cells recruitment of XPF was absent immediately
      after UV and was delayed by 0.5 and 3 h in cells from the mild and severely
      affected XP patients, respectively. Redistribution of NER proteins was nearly
      complete in normal cells by 3 h but by 24 h redistribution was only partially
      present in cells from mild patients and virtually absent in cells from the
      severely affected patients. Ineffectual repair of UV-induced photoproducts
      resulting from delayed recruitment and impaired redistribution of NER proteins
      may contribute to the markedly increased frequency of skin cancer in XP patients.

PMID- 17509952
TI  - Bibliographic characteristics of plastic surgeons in The Netherlands: a 55-year
      survey.
AB  - BACKGROUND: The allotment of grants is increasingly dependent on benchmarking of
      scientific output. Still, data to benchmark such output for plastic surgeons are
      lacking. Therefore, we retrieved these data for plastic surgeons in The
      Netherlands. METHODS: We analysed the bibliographic and some biographic
      characteristics of all 223 plastic surgeons registered in The Netherlands from
      1950 through 2004, as well as of all 61 trainee plastic surgeons. Biographic
      characteristics were obtained through the Netherlands Society of Plastic Surgery
      and bibliographic characteristics were retrieved from PubMed and the Science
      Citation Index. With these data, we established a trend of publications at
      various moments in the careers of plastic surgeons. RESULTS: The age at
      graduation from medical school (27 years) and at the defence of PhD before
      registration (32 years) did not differ between specialists and residents.
      Eighteen residents (0.30) had already obtained a PhD, compared to the 34
      specialists (0.15) who obtained their PhD prior to registration. Specialists made
      2396 contributions to 1758 PubMed-indexed articles and residents made 327
      contributions to 323 articles. Sixty percent of the specialists had published by
      the time of registration, whereas 79% of the current residents had already done
      so. The resident-authors had contributed to more articles (mean 6.8) than their
      predecessors had done at the moment of their registration (mean 4.7). Surgeons
      and residents published the greater part of their work in plastic surgery
      journals with relatively high impact factors. Sixty percent of the articles by
      residents and 45% of the articles by specialists had been cited by others, and
      articles by residents obtained a mean of 3.8 citations as compared to 4.3
      citations to articles by specialist. Most specialists published until six years
      after registration. CONCLUSIONS: The quantity and quality of publications by
      plastic surgeons and residents from The Netherlands increased over the studied 55
      year period. Most specialists published from the moment of their graduation at
      medical school until six years after their registration as plastic surgeon. The
      residents of 2004 published more and better than their predecessors.

PMID- 17509953
TI  - Double innervation occurs in the facial mimetic muscles after facial-hypoglossal
      end-to-side neural repair: rat model for neural supercharge concept.
AB  - BACKGROUND: Double innervation of facial mimetic muscles by both facial and
      hypoglossal nerves after end-to-side neurorrhaphy has not been proven, although
      facial -hypoglossal end-to-side neurorrhaphy has been used in persistent
      incomplete facial palsy recently, and has achieved clinical evidences of recovery
      with rare synkinesis. We established a rat model to compare synkinesis after end
      to-end and end-to-side neurorrhaphy techniques between facial and hypoglossal
      nerves, and confirmed double innervation using retrograde tracers. METHODS: Rats
      were divided into three groups (each consisting of six rats), a facial palsy
      group (Group A), a facial-hypoglossal end-to-end neurorrhaphy group (Group B),
      and a facial-hypoglossal end-to-side neurorrhaphy group (Group C). Eight weeks
      after surgery, synkinesis of the facial mimetic muscles was observed and recorded
      via video camera. In Group C, post operative, intramuscular injections of
      retrograde neural tracers (Fast Blue, Diamidino Yellow and DiI) into the facial
      mimetic muscles were performed to prove double innervation by both the facial and
      hypoglossal nerves. RESULTS: In Group B, all rats showed facial palsy. However
      while eating and drinking, their half of the face showed mass movements (strong
      contraction of whisker pad muscles, curved nose and eye-closure). In Group C,
      four rats showed no significant changes however, two rats showed synkinesis of
      the eyelid while eating and drinking (frequent eye-closure distinguishable from
      the contralateral normal side). In Group C, retrograde tracers injected in the
      mimetic muscles were detected in both the facial and hypoglossal motor nuclei in
      situ of all the rats' brain stem. CONCLUSION: This study proved that double
      innervation of mimetic muscles by both facial and hypoglossal nerves occurs after
      the end-to-side neurorrhaphy. Double-innervated mimetic muscles around the mouth
      after hypoglossal-facial end-to-side neurorrhaphy showed less synkinesis than the
      end-to-end neurorrhaphy.

PMID- 17509954
TI  - The Maltese cross technique: umbilical reconstruction after dermolipectomy.
AB  - A simple and easy technique for reconstruction of the umbilicus was devised, with
      emphasis on forming walls of the umbilicus and a depression in a caudal
      direction. A quite satisfactory result was obtained. A permanent and sufficient
      depression for the umbilicus can be expected as a result of three-dimensional
      formation of walls. We also obtained a natural-looking neo-umbilicus.

PMID- 17509955
TI  - Successful treatment of refractory joint contractures caused by sclerodermatous
      graft versus host disease.
AB  - Sclerodermatous or cutaneous chronic graft versus host disease is characterised
      by deposition of collagen in the skin and possibly other soft tissues, resulting
      in loss of range of motion and functional capabilities. A patient with refractory
      joint contractures caused by sclerodermatous graft versus host disease is
      presented, and the successful surgical management of the case described.

PMID- 17509956
TI  - Primary breast lymphoma in a patient with silicone breast implants: a case report
      and review of the literature.
AB  - Primary breast lymphoma is a rare disease. Estimated incidence is 72 to 910 cases
      per year. We report a patient who developed anaplastic large cell lymphoma in her
      breast adjacent to a silicone breast implant 14 years after elective breast
      augmentation. Metastatic work up revealed no other focus of disease. She was
      treated with systemic chemotherapy. Review of the literature revealed five cases
      of primary breast lymphoma associated with a breast implant. Patients presented
      with either a mass or a periprosthetic fluid collection an average of eight years
      after either silicone gel-filled or saline-filled breast implant placement.
      Diagnosis was obtained with either biopsy or aspiration. All patients had the
      same histological subtype, anaplastic large cell lymphoma. It is unlikely that
      any cause-effect relationship exists between breast implants and primary breast
      lymphoma since chance alone could easily account for the low incidence of primary
      breast lymphoma in patients with breast implants. However, a fluid collection
      around a breast implant may be a unique presentation for this population of
      patients. Clinicians should include malignancy in the differential diagnosis of
      periprosthetic fluid collections and periprosthetic masses. Useful diagnostic
      tests may include MRI, aspiration with cytology, and percutaneous or open biopsy.

PMID- 17509957
TI  - Use of continuous positive airway pressure (CPAP) in neonatal units--a survey of
      current preferences and practice in Germany.
AB  - There is only limited evidence regarding the equipment or the settings (pressure
      and flow) at which CPAP should be applied in neonatal care. Aims of this
      nationwide survey of German neonatal units were to investigate (1) for which
      clinical indications CPAP was employed, (2) which CPAP equipment was used, (3)
      which CPAP settings were applied. A questionnaire on the use of CPAP was sent to
      all children's hospitals in Germany. Data were stratified and compared by level
      of medical care provided (non-academic children's hospital, academic teaching
      hospital and university children's hospital). 274 institutions were contacted by
      mailed questionnaire. The response rate was 86%, 90 non-academic children's
      hospitals, 119 academic teaching hospitals and 26 university children's hospitals
      replied. (1) There were no statistically significant difference in CPAP use
      between the institutions: 231 (98%) used CPAP for treating respiratory distress
      syndrome, 225 (96%) for treating apnoea-bradycardia-syndrome and 230 (98%)
      following extubation. (2) Commercial CPAP systems were employed by 71% of units,
      the others used a combination of different devices. Respirator generated CPAP was
      most commonly used. Exclusively mononasal CPAP was used by only 9%, and binasal
      CPAP by 55% of institutions. (3) Median CPAP was 4.5 cm H2O (range 3-7), median
      maximum CPAP was 7 cm H2O (range 4-10), with no statistically significant
      differences between the hospitals. CONCLUSION: Between units, CPAP was given via
      a broad range of CPAP systems and at varying pressure settings. The reported
      differences reflects personal experiences and preferences, rather than sound
      evidence from clinical trials.

PMID- 17509958
TI  - Vascular endothelial growth factor, lipoporotein-associated phospholipase A2, sP
      selectin and antiphospholipid antibodies, biological markers with prognostic
      value in pulmonary hypertension associated with chronic obstructive pulmonary
      disease and systemic lupus erithematosus.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PH) is a progressive disease with a
      poor prognosis that ultimately leads to right ventricular failure and death. The
      pathogenesis of severe PH seems to be related to inflammatory responses and
      coagulation disturbances. Many diseases can develop PH in their course, thus
      aggravating their outcome. The objective was to investigate the values of
      vascular endothelial growth factor (VEGF), sP-selectin, lipoprotein-associated
      phospholipase A2 (PLA2-LDL), antiphospholipid antibodies (APLA) and their
      relation with PH, in systemic lupus erythematosus (SLE) and chronic obstructive
      pulmonary disease (COPD), two conditions in which the occurrence of PH is
      frequent. DESIGN: Prospective clinical study. SETTING: A University Department of
      Internal Medicine, a National Institute of Research. PATIENTS: 30 SLE patients
      (15 patients without PH (group I) and 15 patients with PH group II)), 30 patients
      with COPD (15 patients without PH (group III) and 15 patients with PH (group IV))
      and 10 healthy controls, selected by clinical, immunological, echocardiographical
      criteria and pulmonary functional tests. MAIN OUTCOME MEASURES: VEGF, sP-selectin
      and PLA2-LDL level in plasma and presence of antiphospholipids antibodies (lupus
      anticoagulant, anticardiolipin and anti beta2 GPI) in plasma. - RESULTS: In
      patients with PH, the values of VEGF were significantly increased [group II
      (1023.1) and IV (904.3)] compared with group I (744.2), III (356.4), and controls
      (330.3). The values of sP-selectin in group II (9.7), and IV (10.4) were also
      increased compared with controls (6). APLA were present in all patients in group
      II (100%), and in 8 patients in group IV (53%), while in the other groups the
      frequency was low (33% group I and 13% group III). PLA2-LDL activity was higher
      in group II (429.1) and group IV (394.5) than in group I (317.8), group III
      (343.2) and controls (256.3). CONCLUSION: PH is a severe complication in COPD and
      SLE. The increased values of VEGF, PLA2-LDL and P-selectin in patients with long
      standing PH are related to severe endothelial dysfunction and may have prognostic
      values. APLA may have pathogenic value in SLE patients with PH. APLA are possibly
      implicated in the pathogenesis of PH in these diseases. VEGF, APLA and sP
      selectin may constitute new therapeutic targets for PH.

PMID- 17509959
TI  - N-terminal pro-B-type natriuretic peptide (NT-proBNP) in HIV-1 infected
      individuals on HAART.
AB  - BACKGROUND: Studies suggest that highly active anti-retroviral therapy (HAART)
      prolongs life in HIV infected individuals and that HIV infected individuals
      increasingly suffer from cardiovascular complications. NT-proBNP has been shown
      to represent an indicator of cardiac function. METHODS: 495 HIV infected
      individuals under HAART and 1980 blood donors (BD) were tested for N-terminal pro
      B-type natriuretic peptide (NT-proBNP). NT-proBNP was performed by an automated
      electrochemiluminescence immunoassay (ECLIA) method. RESULTS: HIV infected
      individuals had significantly higher NT-proBNP levels than age matched blood
      donors (18-29 y: median: 33 pg/ml HIV vs. 5 pg/ml BD; p = 0.0247; 30-39 y:
      median: 25 pg/ml HIV vs. 5 pg/ml BD; p = 0.0351; 40-49 y: median: 35.5 pg/ml HIV
      vs. 5 pg/ml BD; p < 0.0001; 50-59 y: median: 42 pg/ml HIV vs. 36 pg/ml BD; p =
      0.3665; 60-69 y: median: 82.5 pg/ml HIV vs. 46 pg/ml BD; p = 0.0055) the effect
      was consistently found in all age and both gender groups. HIV infected
      individuals differed from the blood donor control group with respect to
      cardiovascular risk factors (hypertension, cardiovascular (CV) medication,
      diabetes mellitus, smoking status). In HIV infected individuals NT-proBNP levels
      did not correlate to cardiovascular risk factors including GFR except for C
      reactive protein (CRP) levels using multivariate analysis. There was also no
      evidence for cardiotoxic effects due to HAART or specific antiretroviral drugs.
      High NT-proBNP levels were found in Hepatitis C virus (HCV) infected individuals
      who had received alpha-interferon therapy. CONCLUSIONS: HIV infected individuals
      had higher NT-proBNP levels than age matched blood donors possibly as a result of
      a higher prevalence of general cardiovascular risk factors and HIV associated
      risk factors, the finding is consistent with an increased incidence of
      cardiovascular events described in HIV infected individuals. Further studies on
      the relationship to cardiovascular outcome are warranted.

PMID- 17509960
TI  - MR-guided interstitial laser thermotherapy of colorectal liver metastases:
      efficiency, safety and patient survival.
AB  - PURPOSE: Evaluation of MR-guided interstitial laser thermotherapy (ILT) of
      colorectal liver metastases under consideration of efficacy, safety and patient
      survival. MATERIALS AND METHODS: Sixty-six inoperable patients with a total of
      117 colorectal liver metastases were treated with MR-guided laser therapy in 96
      sessions. 40.9% of patients presented metastases from rectum carcinoma, 30.3%
      from sigmoid carcinoma and 28.8% from colon carcinoma. Inclusion criteria were <
      or =5 metastases < or =5 cm in greatest diameter and no extrahepatic tumor
      spread. Internally water-cooled 9F power-laser-applicators were placed under CT
      fluoroscopy. For MR-guided ILT, a 1064 nm Nd-YAG-lasers with a beam divider with
      multi applicator technique was used. The energy applied was 10 watt per
      centimeter diffusor length, with the diffusor length ranging from 20 to 40 mm.
      The mean duration of the energy application was 23 minutes (range: 15 - 37
      minutes). The endpoint of the laser ablation was defined as the absence of
      hyperintense tumor tissue in the continuously monitored T2-w fat saturated
      gradient-echo sequences. Follow-up included contrast-enhanced MRI using T1- and
      T2-weighted spin-echo and gradient-echo sequences every three months after
      treatment. Survival times were calculated using the Kaplan-Meier method. RESULTS:
      The median follow-up was 8.7 months (mean 11.8; standard deviation 9.9; range 1
      to 36). The overall median progression free survival was 6.1 months (range, 0.3
      to 27+ months). Median survival was 23 months (95% CI, 17-29 months). The rate of
      major complications was 2.1% (n = 2) and peri-procedural mortality (30 days) was
      3% (n = 2). After 3, 6, 9, and 12 months, local tumor control was 98.3%, 91.4%,
      76.1%, and 69.4%, respectively. In no patient metastatic deposits along the
      catheter access route were found. CONCLUSIONS: In patients with colorectal liver
      metastases, interstitial laser thermotherapy is an effective and safe therapeutic
      option and therefore suitable not only in palliative situations.

PMID- 17509961
TI  - Management of Fournier's gangrene--report of 7 cases and review of the
      literature.
AB  - Fournier's gangrene is a rare infection characterized with fast-progressing
      myonecrosis, that affect regions of perineum, genitalia and perianal area. This
      retrospective study presents authors' experiences and their principles in early
      diagnosis and treatment of Fournier's gangrene. The goal of this paper is to
      point out numerous diagnostically and therapeutic difficulties that lead to a
      high mortality if not recognized in time. We here describe seven male patients
      with myonecrosis and necrotising fasciitis in scrotal, perianal and perineal
      regions. Average age was 61 years (form 57 to 66 years of age), and average
      length of treatment was 25.8 days (from 14 to 36 days), with lethality of 14%
      (one case). We have recognised diabetes mellitus as risk factor, together with
      urethrostenosis, and other diseases of the perianal region (hemorrhoids, anal
      fissure, abscesses). Our hypothesis is that the key of the successful treatment
      is to treat as soon as symptoms onset, early and aggressive necrectomy under
      broad antibiotic protection. We also emphasize the possibility of recurrence of
      this disease even several years after treatment.

PMID- 17509962
TI  - Quantitative EEG findings in patients with chronic renal failure.
AB  - OBJECTIVE: Chronic renal failure frequently causes uremic encephalopathy with
      impairment of various cognitive functions, but the pathophysiology of uremic
      syndrome is complex and poorly understood. In this study, we wished to establish
      a reliable tool and monitor system to evaluate the central nervous system
      dysfunction of patients with uremic encephalopathy. METHODS: A group of 31
      patients with chronic renal failure was assessed with online real time brain
      mapping using the CATEEM technology to detect deviations and abnormal EEG
      patterns. Quantitative EEG data were compared with those of an age-matched
      healthy control group and correlated to laboratory markers and various dosages of
      erythropoietin. RESULTS: Electrical power was most prominent in delta, theta and
      alpha frequencies in the temporal and central brain areas (electrode positions
      T5, T6, C3 and C4). Explorative statistical comparison of the two data sets with
      respect to these brain areas revealed that the increases in electrical power in
      delta, theta and alpha frequency bands were different from healthy people with p
      values of p<0.003 (delta), p<0.0003 (theta), p<0.01 (alpha 1) and p<0.01 (alpha
      2). In addition, high levels of hemoglobin were significantly correlated with
      higher theta activity. CONCLUSION: We detected distinct EEG deviations from
      normality in patients with chronic renal failure. Online real time brain mapping
      using the CATEEM technology provides a unique possibility to monitor mental
      impairment and serves as a control for therapeutical intervention.

PMID- 17509963
TI  - Cotton wool spots should not be regarded as retinal nerve fibre layer infarcts.

PMID- 17509964
TI  - Brain abscess caused by Streptococcus pneumoniae with acute onset and rapid
      progressive symptoms.
AB  - Although the decline of the morbidity and mortality in recent years, brain
      abscess is still an important problem in neurocritical care medicine and remains
      a serious illness that can result in severe disability or even death, especially
      if misdiagnosed or managed improperly. We report a very rare case of a patient
      who developed a bacterial brain abscess in the posterior fossa with an atypical
      rapid progression of neurological symptoms. Furthermore, MRI demonstrated
      additional brain stem and left hemispheric lesions. Early onset broad antibiotic
      therapy, corticosteroid application and extensive intermediate care management
      was leading to a complete regression of the initially dramatic symptoms.

PMID- 17509965
TI  - Fatal pneumonia associated with human metapneumovirus (HMPV) in a patient with
      myeloid leukemia and adenocarcinoma in the lung.
AB  - We describe a clinical case of a 59 old caucasian male who was delivered to the
      hospital for severe pneumonia associated to human metapneumovirus. The patient
      suffered from a leukemia and an adenocarcinoma in the lung and died two weeks
      after submission due to fatal respiratory failure.

PMID- 17509966
TI  - Occupational and leisure-time energy expenditure and body mass index.
AB  - OBJECTIVES: Almost all over the world, both high- and low-income countries have
      been experiencing the obesity epidemic. The aim of the study was to evaluate the
      association between occupational energy expenditure and body mass index (BMI).
      MATERIALS AND METHODS: The study was performed in a randomly selected group of
      508 full-time employees, including 272 men (mean age, 42.6 +/- 10.6 years) and
      236 women (mean age, 41.5 +/- 9.9 years). Logistic regression was used to
      estimate odds ratios and 95% confidence intervals as well as to control the
      effects of occupational workload and BMI. Physical activity was determined by the
      Seven Day Physical Activity Recall (SDPAR). RESULTS: The multifactorial logistic
      regression analysis did not indicate that weekly energy expenditure on
      occupational physical activity (kcal/week) was linked with the risk for BMI over
      25 (kg/m). But leisure-time physical activity (LTPA) was associated with BMI
      level in both men and women. In the group of men declaring no energy expenditure
      on physical activity, the risk for BMI > 25 (kg/m) was significantly higher than
      among men expending 1000 kcal/week or more on LTPA (adjusted OR = 1.05; 95%CI:
      1.03-2.27). Also, among women not taking up any recreational physical activity,
      the risk of BMI > 25 (kg/m) was higher than in females, reaching a satisfactory
      level of recreational physical activity (adjusted OR = 2.39; 95%CI: 1.07-7.42). A
      higher educational attainment and a higher socioeconomic status were also
      associated with a lower risk of unhealthy body weight in the study participants.
      CONCLUSIONS: Prophylactic schedules associated with management of overweight and
      obesity should be addressed to all adults, above all to older age groups. Future
      programs aimed at decreasing the spread of overweight and obesity in adults
      should consider an improvement in health habits, including leisure-time physical
      activity and diet as well as socioeconomic factors. Targeted health education
      interventions should assist in reducing the obesity epidemic.

PMID- 17509967
TI  - Work-related respiratory symptoms among cotton-fabric sewing workers.
AB  - OBJECTIVES: An inspection of the sewing unit in a 700-bed hospital revealed that
      workers employed in this unit complained of cough, shortness of breath, and
      tightness in the chest. The aim of this cross-sectional study was to assess the
      prevalence of respiratory symptoms in the sewing workers and dust concentration
      in the workplace. The obtained results were compared with the control group.
      MATERIALS AND METHODS: The sewing workers (n = 22, including 19 current and 3
      former employees) and 22 housekeepers as controls were included in the study. All
      the participants responded to the respiratory questionnaire and underwent
      spirometric measurements, skin prick test, chest X-ray, and methacholine
      inhalation test. Environmental dust was measured using both an air pump and a
      vertical elutriator. RESULTS: The sewing workers reported more symptoms of
      phlegm, chest tightness and eye irritation than persons of the control group.
      Neither clinical investigations nor respiratory disorders under study provided
      evidence for a significant difference between the sewing workers and the control
      group. Of the 22 subjects, 2 (9.1%) showed occupational asthma and 4 (18.2%)
      mucous membrane irritation and organic dust toxic symptoms. The total and
      respiratory dust was within normal limits, but the dust concentration measured by
      the elutriator was above the limit value of 0.34 +/- 0.09 mg/m. After ventilation
      improvements, the dust level decreased to 0.19 +/- 0.06 mg/m. CONCLUSIONS: This
      study indicated that respiratory and ocular disorders were related to organic
      dust produced during the sewing process of cotton fabric.

PMID- 17509968
TI  - Acute poisonings registered since 1970: trends and characteristics. Analysis of
      the files collected in the National Poison Information Centre, Lodz, Poland.
AB  - OBJECTIVES: The aim of the presented study was to trace the trends and
      characteristics of acute poisonings in Poland, including the rate, type, and
      causal agents, over a long period of time (1970-2000) to define the dynamics of
      changes and major causes of poisoning-related mortality. MATERIALS AND METHODS:
      The analysis was based on the data obtained from the patients' records submitted
      by all poison centers in Poland (Gdansk, Krakow, Lublin, Lodz, Poznan, Sosnowiec,
      Rzeszow, Warszawa, and Wroclaw). RESULTS: Drugs were the most frequent group of
      chemical substances, responsible for more than 50% of all admissions because of
      acute poisonings. From 1980, the rate of drug poisonings showed a slightly
      downward trend from 56.4% in 1980 to 48.8% in 2000. Ranked second with respect to
      the prevalence rate were alcohol poisonings. A clear upward trend from 8.0% in
      1980 to as high as 30.8% in 2000 was noted in this category. Poisonings with
      carbon monoxide became less frequent, ranging from 15.3 to 5.1%, respectively in
      the aforesaid years. The percentage of poisonings with pesticides, corrosives and
      metal compounds have been reduced in recent years. The greatest number of lethal
      outcomes was also due to poisonings with alcohols and drugs. The highest
      mortality ratio was recorded for ethylene glycol, methanol and Amanita phalloides
      poisonings. CONCLUSIONS: A constantly growing number of acute poisonings in
      Poland makes it necessary for all the medical and other professionals involved
      (clinical toxicologists, diagnostic laboratory staff, and poison information
      specialists) to enhance and coordinate their efforts. These activities should be
      focused on: (a) better and faster accessibility of all information on the agent
      of poisoning, possible health effects, and methods of treatment to support the
      medical staff; (b) selection of the most effective methods to eliminate poisons
      from the system and improve further therapy, and (c) better accessibility of
      antidotes.

PMID- 17509969
TI  - New method of visual disturbances assessment in pilots during tests in the Polish
      human centrifuge.
AB  - OBJECTIVES: Visual disturbances are commonly accepted criteria for acceleration
      tolerance assessment. Researchers during centrifuge experiments use them as a
      safe criterion for cessation of acceleration exposure. Visual disturbances
      analysis is a non-invasive method of assessing retinal blood flow. Limitation of
      visual stimuli perception is a measure of physiological state of the experiment
      participants before hemodynamic changes, which reach a critical level manifested
      by G-induced loss of consciousness. Detection of these disturbances play an
      important role during the acceleration tolerance assessment. In this study, an
      attempt was made to answer the question on how many mistakes or incorrect
      reactions had to be identified to classify the ability of the pilot to fly on
      military jets. MATERIALS AND METHODS: A new computer-aided research apparatus of
      our own design was used to assess visual disturbances, being a criterion of +Gz
      tolerance. In the center of monitor screen, a line of 3 light points was
      projected. During the centrifuge test, green lateral lights randomly changed
      their shapes from circles to squares while central light, being a point of vision
      fixation, remained unchanged. To assess its efficacy, 14 volunteers participated
      in the tests with various stimuli exposure. The authors aimed at selecting
      parameters of stimuli and exposure so that the division of reactions presented in
      the table would correspond with the score scale appropriate for our goals.
      RESULTS: Preliminary tests showed that appropriately selected light intensity of
      the exposed stimuli enables the use of test results to assess the number of
      erroneous reactions, and consequently the level of pilots' concentration during
      centrifuge tests. CONCLUSIONS: It has been found that the chosen luminance range
      of the projected light points is correct as it allows to evaluate the reactions,
      which should be considered erroneous. Additionally, prolongation of the correct
      reaction time to the mean value of about 400 ms facilitates better
      differentiation of results. Proper results evaluation, depending on the number of
      errors, lack of reactions or prolonged reactions made the assessment easier with
      computer-aided methods.

PMID- 17509970
TI  - Biomonitoring of cyanobacterial blooms in Polish water reservoir and the
      cytotoxicity and genotoxicity of selected cyanobacterial extracts.
AB  - OBJECTIVES: Water pollution with toxic cyanobacterial blooms is a worldwide
      problem. Cyanobacteria species that mainly produce microcystins predominate in
      Polish water reservoirs. MATERIALS AND METHODS: In our study, cyanobacterial
      blooms were monitored during summer of 2004 in the Sulejow reservoir. The
      concentration of microcystins in water and cyanobacterial cells were determined
      using liquid chromatography and immunobiotests, while the biological activity of
      microcystic cyanobacterial extracts was assessed using bacterial tests (SOS
      Chromotest, UMU test), the comet assay and micronucleus test with human
      lymphocytes. RESULTS: It was revealed that cyanobacterial bloom was most
      intensive in mid August and lasted until the end of September. Microcystis
      aeruginosa and Aphanizomenon flos-aquae dominated in the blooms. The highest
      concentration of microcystins in cyanobacterial cells was also observed at that
      time. The concentration of microcystins in water did not exceed 1 microg/l. All
      cyanobacterial extracts showed weak genotoxicity only for Escherichia coli PQ37.
      The cyanobacterial extracts prepared at the beginning of September were most
      toxic to human lymphocytes, the effective microcystin extracts (EC50)
      concentration was about two or three times lower compared to the other extracts.
      The level of DNA damage in lymphocytes after short exposure to microcystic
      extracts (3 and 6 h) was significantly higher than respective levels after longer
      exposure. The microcystins of cyanobacterial blooms induced a slight increase in
      micronuclei frequencies in human lymphocytes. CONCLUSION: Phytoplankton biomass
      and the genotoxicity of massive cyanobacterial blooms should be assessed for
      eucariotic cells in the Sulejow reservoir to avoid the hazard induced by
      cyanobacterial blooms.

PMID- 17509971
TI  - [Clinical pharmacologic principles of the development and application of follow
      on biological medicinal products].
AB  - The structure of the biological drug proteins cannot be unequivocally determined
      due to their large molecular weight and complex structure. As a consequence, the
      production of a follow-on biological product completely identical with the
      originator molecule is not possible yet. In order to emphasize this difference
      the European Medicines Agency (EMEA) restricted the term of generic medicines
      exclusively to follow-on drugs containing small molecular weight, precisely
      identifiable chemicals as the active agent. In the case of follow-on medicines
      containing large molecular weight proteins as the active ingredient, the term
      similar biological medicinal product was introduced. The similarity of the
      pharmacokinetic properties, the effectiveness, safety and the quality of the
      follow-on drug must be proven in comparative studies with the reference
      biological product. For the evaluation of the possible differences in the
      immunogenicity of the originator and follow-on products, long-term observations
      have to be carried out with the biosimilar drugs even after marketing
      authorization has been obtained. The evaluation of adverse reactions should be
      done separately for each biosimilar product.

PMID- 17509972
TI  - [Novel therapeutic approaches in the treatment of irritable bowel syndrome].
AB  - The treatment of irritable bowel syndrome due to the heterogeneous clinical
      symptoms and coexisting psychiatric disorders is still controversial. Although
      several agents with different mechanisms of action are widely used in clinical
      practice, there are only few drugs available with strong evidence of their
      efficacy, safety and tolerability at present. The etiology of irritable bowel
      syndrome is considered to be multifactorial: experimental and clinical research
      on visceral hypersensitivity, motility and brain-gut axis involving its
      neurotransmitters and receptors created the foundation of novel therapeutic
      approaches. Albeit nowadays several drugs (alosetron, tegaserod) have been
      registered in a few countries for the treatment of irritable bowel syndrome,
      further large clinical trials are required related to the new chemical entities.

PMID- 17509973
TI  - [Survival reflecting the effectiveness of primary operation in patients with
      epithelial ovarian cancer].
AB  - INTRODUCTION: Primary operation of ovarian cancer patients has a great
      implication in treatment. The survival of patients operated on optimally is
      better than in those patients, who have tumor residuum after the operation. The
      optimal result is more frequent in operations performed by gynecologist
      oncologists as is in surgery administered by general gynecologists or general
      surgeons. AIM: Authors evaluated the data of 83 epithelial ovarian cancer
      patients treated by first-line paclitaxel-carboplatin chemotherapy in
      Gynecological Oncology Department, at National Institute of Oncology between 2000
      2002 through a 35 months follow-up period. MATERIAL AND METHODS: Average age of
      patients was as 59 +/- 9.8 years. Primary optimal surgery was done in 45, non
      optimal operations were administered in 38 patients. Distribution of patients
      according to the stages was similar in both groups. Evaluation of progression
      free interval was calculated according to the product limit method of Kaplan
      Meier. RESULTS: Progression free interval was 35 and 35 months in the optimal and
      non-optimal surgery groups and 36 and 35 months in the groups operated on by
      skillful or less practiced gynecologists in radical surgery. Gynecologist
      oncologists' first operations showed an optimal result in 76% of patients,
      contrary to other surgeons' group resulting in only a 43% first optimal surgery.
      A better progression free interval was observed in the patients having optimal
      surgery by the interval laparotomy in contrary to those patients, who had no
      optimal second operation (36 vs 25 months), however, the difference showed no
      statistical significance. CONCLUSION: Authors believe the similar survival data
      could be caused by the short follow-up (35 months) and the small numbers in the
      patient-groups as well as the greater rate of advanced stage patients in the
      authors' department, in contrary to the partner municipal hospitals (23/29 = 80%
      versus 33/54 = 61%) resulting in worse survival chances. Proving the efficiency
      of radical surgery the survey is carried on.

PMID- 17509974
TI  - [Detection of Toxoplasma gondii in amniotic fluid using quantitative real-time
      PCR method].
AB  - INTRODUCTION: The infection caused by parasite Toxoplasma gondii is often
      asymptomatic or a mild clinical disease. Congenital toxoplasmosis is the result
      of transplacental transmission of Toxoplasma gondii from an acute infected
      mother. Toxoplasmosis can cause several fetal symptoms. Early diagnosis of the
      infection can enhance the success of the medical treatment. Congenital
      toxoplasmosis can be detected by serological or PCR amplification methods. AIMS:
      The authors decided to develop a quantitative real-time PCR technique for
      detection of T. gondii in amniotic fluid samples. METHODS: DNA was isolated using
      silica adsorption method. Quantitative real-time PCR method was used to detect T.
      gondii infection in the samples. RESULTS: From the studied 74 samples in 6 cases
      T. gondii was detected. CONCLUSION: The introduced quantitative real-time PCR
      method is a fast and sensitive PCR based method and makes possible the
      quantification of the protozoa number in the sample.

PMID- 17509975
TI  - [Internet-based biobank-registers in Hungary].
AB  - Genomic studies - such as genotype-phenotype interactions and gene expression
      studies - play an increasing role in biomedical research. Obviously, these
      studies strongly depend on specimen-collections of the affected individuals.
      Collected, stored and registered specimens along with available clinical data
      represent a biobank. - Collaboration of the owners of biobanks and sharing the
      specimen collections increase the efficiency of research. This paper presents
      Hungarian initiatives aiming at establishing biobank-registers, identification
      and harmonization of the work of individual biobanks. The authors present the
      structure and aims of Hungarian Biobank homepage, Semmelweis Biobank, rare
      disease-specified Orphanet and NEPSYBANK specified on neuropsychiatric research. 
      During these years several new biobanks are established for genomic studies.
      Probably this process will accelerate significantly in the nearest future, when
      specific statute will regulate the establishment and maintenance of biobanks. It
      is presumed that the presented biobank-networks would help the coordination.

PMID- 17509976
TI  - [Correlation of pharmacy and the law in Hungary].

PMID- 17509977
TI  - [HORUS column of Orvosi Hetilap (Medical Weekly)].

PMID- 17509978
TI  - [Colitis ulcerosa].

PMID- 17509981
TI  - Synopses, systems, and synergism.

PMID- 17509982
TI  - T-cell large granular leukemia and related proliferations.
AB  - Session 9 of the 2005 Society for Hematopathology/European Association for
      Haematopathology Workshop focused on large granular lymphocyte (LGL) leukemias
      and related disorders. T-cell LGL (T-LGL) leukemias, discussed herein, account
      for 2% to 3% of cases of small lymphocytic leukemia. T-LGL diseases cover a
      heterogeneous spectrum of disorders that include reactive conditions, typically
      associated with autoimmune disease, to outright leukemia. These disorders are
      found in older people, with an average age at initial examination of
      approximately 60 years and a median survival of more than 10 years in T-LGL
      leukemia. Systemic symptoms and neutropenia are common at initial examination.
      Lymphocytosis, composed of small mature lymphocytes with increased cytoplasm, is
      common. The spleen and bone marrow are involved in T-LGL leukemia, although
      morphologic findings may be subtle. The immunophenotype is typically that of
      CD3+/CD8+ cytotoxic T cells. Some cases may be due to chronic immune stimulation,
      with subsequent clonal escape and proliferation of a neoplastic population of
      lymphocytes.

PMID- 17509983
TI  - NK-cell lymphomas and leukemias: a spectrum of tumors with variable
      manifestations and immunophenotype.
AB  - Natural killer (NK) cells are lymphocytes that have some phenotypic and
      functional similarities to cytotoxic T cells but do not express the T-cell
      receptor complex. NK-cell malignancies may be localized or disseminated at
      initial examination, and most behave aggressively. The variable presentation of
      NK-cell lymphomas and leukemias suggests that they represent a spectrum of
      disease, with Epstein-Barr virus (EBV) implicated in the pathogenesis of most
      cases. Using cases presented in Session 10 of the 2005 Society for
      Hematopathology/European Association for Haematopathology Workshop on T-cell and
      NK-cell malignancies, we discuss outstanding issues in the classification and
      diagnosis of NK-cell malignancies. These difficulties are related to unusual
      sites of manifestation, atypical immunophenotypic features, and EBV+ T-cell
      tumors that resemble classical extranodal NK/T-cell lymphoma, nasal-type (EN-NK/T
      NT). Although some of these cases can be grouped into ENNK/T-NT, classification
      of tumors that have atypical or discordant features will remain controversial,
      particularly when EBV is absent.

PMID- 17509984
TI  - Hepatosplenic and other gammadelta T-cell lymphomas.
AB  - The 2005 Society for Hematopathology/European Association for Haematopathology
      Workshop session 11 was dedicated to hepatosplenic T-cell lymphoma (HSTCL). HSTCL
      is a rare aggressive type of extranodal lymphoma characterized by
      hepatosplenomegaly, bone marrow involvement, and peripheral blood cytopenias.
      HSTCL exhibits a distinctive pattern of infiltration; tumor cells preferentially
      infiltrate the sinusoids of the splenic red pulp, liver, and bone marrow. The
      tumor cells have a nonactivated cytotoxic T-cell immunophenotype and frequently
      carry a recurrent cytogenetic abnormality, isochromosome 7q. Most cases express
      the gammadelta T-cell receptor, but cases can have an alphabeta phenotype and are
      considered to be a variant of the disease. Although HSTCL is the prototype
      peripheral T-cell lymphoma expressing the gammadelta T-cell receptor, non-HSTCL
      proliferations of gammadelta T cells can involve other extranodal sites, mainly
      skin and mucosa. These gammadelta T-cell lymphomas display marked heterogeneity
      in clinical and histologic features. In contrast with HSTCL, non-HSTCL gammadelta
      T-cell lymphomas frequently have an activated cytotoxic phenotype and most likely
      are not a single disease entity.

PMID- 17509985
TI  - The immunophenotypic attributes of NK cells and NK-cell lineage
      lymphoproliferative disorders.
AB  - Natural killer (NK) cells are a distinct lymphocyte subset that, like cytotoxic T
      cells, recognize and destroy abnormal self-cells. Unlike T cells, however, NK
      cells lack a uniquely rearranged antigen receptor gene or a single defining
      immunophenotypic attribute. Furthermore, there is considerable functional and
      phenotypic overlap between NK cells and cytotoxic T cells, and the latter are
      induced by cellular activation to express many NK-associated antigens. These
      factors all contribute to difficulties in recognizing abnormal NK-cell expansions
      and distinguishing them from cytotoxic T cells in the clinical laboratory.
      Recently, new classes of NK-associated major histocompatibility complex receptors
      have been described that can be of value in evaluating NK-cell and cytotoxic T
      cell populations. In this review, immunophenotyping approaches using antibodies
      to traditional and novel T- and NK- associated antigens that can be used to
      evaluate these cell types and diagnose NK-cell and cytotoxic T-cell disorders in
      the clinical laboratory setting are discussed.

PMID- 17509986
TI  - T-cell and NK-cell posttransplantation lymphoproliferative disorders.
AB  - Posttransplantation lymphoproliferative disorders (PTLDs) of T-cell or natural
      killer (NK)-cell origin are an uncommon heterogeneous group of lymphoid
      proliferations that fulfill the criteria for one of the T- or NK-cell
      lymphomas/leukemias. This report summarizes 130 T/NK-cell PTLDs reported in the
      literature or presented at the Society for Hematopathology/European Association
      for Haematopathology Workshop on T/NK-cell malignancies. The T/NK-cell PTLDs
      occur at a median of 66 months following transplantation and are usually
      extranodal. The most common types reported are peripheral T-cell lymphoma,
      unspecified, and hepatosplenic T-cell lymphoma. Approximately one third are
      Epstein-Barr virus (EBV)+. The median survival is 6 months. EBV+ cases have a
      significantly longer survival than EBV- cases, even when indolent T-cell large
      granular lymphocytic leukemias are included among the EBV- cases. Many T/NK-cell
      PTLDs have been treated with chemotherapy, often together with decreased
      immunosuppression, but there are infrequent patients who have done well without
      chemotherapy or radiation.

PMID- 17509987
TI  - Synoptic reporting in tumor pathology: advantages of a web-based system.
AB  - The American College of Surgeons Commission on Cancer (ACS-CoC) mandates that
      pathology reports at ACS-CoC-approved cancer programs include all scientifically
      validated data elements for each site and tumor specimen. The College of American
      Pathologists (CAP) has produced cancer checklists in static text formats to
      assist reporting. To be inclusive, the CAP checklists are pages long, requiring
      extensive text editing and multiple intermediate steps. We created a set of
      dynamic tumor-reporting templates, using Microsoft Active Server Page (ASP.NET),
      with drop-down list and data-compile features, and added a reminder function to
      indicate missing information. Users can access this system on the Internet,
      prepare the tumor report by selecting relevant data from drop-down lists with an
      embedded tumor staging scheme, and directly transfer the final report into a
      laboratory information system by using the copy-and-paste function. By minimizing
      extensive text editing and eliminating intermediate steps, this system can reduce
      reporting errors, improve work efficiency, and increase compliance.

PMID- 17509988
TI  - Advantages and disadvantages of serum cholesterol determination by the kinetic vs
      the end point method.
AB  - Enzymatic assays for cholesterol determination can use an end point or a kinetic
      method. We evaluated and compared the performance of these methods. We
      constructed user-defined methods on 3 automated analyzers using Streptomyces
      cholesterol reagents to evaluate the analytic performance of both methods.
      Linearity (700-900 mg/dL) and stability of reagents (5-11 weeks) depended on the
      analyzers. The coefficients of variation for imprecision were 2.41% to 2.99% and
      3.78% to 5.52% for the end point and kinetic methods, respectively. The end point
      method showed less bias at decision cut points (-0.8% to 1.3%) than did the
      kinetic method (-1.1% to 3.6%) but was more affected by interfering
      substances.The advantages of the end point over the kinetic method are better
      precision and lower reagent cost. The end point imprecision fell within National
      Cholesterol Education Program guidelines (<or=3%), but the kinetic did not. The
      kinetic method showed less interference and required shorter analysis time.

PMID- 17509989
TI  - Accuracy of roche accu-chek inform whole blood capillary, arterial, and venous
      glucose values in patients receiving intensive intravenous insulin therapy after
      cardiac surgery.
AB  - Intravenous insulin protocols are increasingly common in the intensive care unit
      to maintain normoglycemia. Little is known about the accuracy of point-of-care
      glucometers for measuring glucose in this patient population or the impact of
      sample source (capillary, arterial, or venous whole blood) on the accuracy of
      glucometer results. We compared capillary, arterial, and venous whole blood
      glucose values with laboratory plasma glucose values in 20 patients after cardiac
      surgery. All 4 samples (capillary, arterial, and venous whole blood and
      laboratory plasma glucose) were analyzed hourly for the first 5 hours during
      intravenous insulin therapy in the intensive care unit. There were no significant
      differences between median capillary whole blood (149 mg/dL [8.3 mmol/L]) and
      laboratory plasma (151 mg/dL [8.4 mmol/L]) glucose levels. The median arterial
      (161 mg/dL [8.9 mmol/L]) and venous (162 mg/dL [9.0 mmol/L]) whole blood glucose
      levels were significantly higher than the median laboratory plasma glucose level.
      Capillary whole blood glucose levels correlate most closely with laboratory
      plasma glucose levels in patients receiving intensive intravenous insulin therapy
      after cardiac surgery.

PMID- 17509990
TI  - The diagnostic role of claudins in serous effusions.
AB  - We analyzed the diagnostic role of claudins in effusion cytology in 325
      effusions, including 218 ovarian, 49 breast, 15 cervical or endometrial, 10
      gastrointestinal, and 8 lung adenocarcinomas and 25 malignant mesotheliomas
      (MMs). Specimens were analyzed for claudin-1 and claudin-3 expression using
      immunohistochemical analysis. Ovarian and breast adenocarcinoma were further
      analyzed for claudin-7 expression. Claudin-1 expression was most frequent in
      ovarian and cervical or endometrial adenocarcinoma compared with other
      adenocarcinomas and MMs (P < .001). Claudin-3 expression was comparable in
      adenocarcinomas of different origin but was absent in MMs (P < .001). Reactive
      mesothelial cells rarely expressed claudins. Claudin-7 expression was higher in
      ovarian than in breast adenocarcinoma (P < .001). Our data suggest that
      expression of claudin-3 or claudin-7 is specific for adenocarcinoma and rules out
      the diagnosis of cells as mesothelial and that absence of claudin-1 expression
      excludes ovarian carcinoma as the possible origin of metastatic adenocarcinoma.
      Claudins may, therefore, be of diagnostic value in effusion cytology.

PMID- 17509991
TI  - A multinational, internet-based assessment of observer variability in the
      diagnosis of serrated colorectal polyps.
AB  - This Internet-based quiz (http://kathrin.unibas.ch/polyp/) tested the diagnostic
      variability of 168 pathologists in the diagnosis of 20 colorectal polyps on 3
      representative images, including hyperplastic polyps (HPs), traditional serrated
      adenomas (TSAs), sessile serrated adenomas (SSAs), and tubulovillous adenomas
      (TVAs). Interobserver variability for each of the 20 lesions was significant and
      was most pronounced for SSAs. Correct answers were independent of the
      participant's experience with TVAs, HPs, and TSAs. Participants with
      gastrointestinal subspecialty training and those who had read a reference article
      on serrated polyps gave a significantly higher percentage of correct answers for
      SSAs. The nomenclature used for serrated polyps was generally inconsistent. Our
      results suggest significant shortcomings in the routine H&E diagnosis of serrated
      colorectal polyps. A diagnostically unifying concept for lesions of the serrated
      neoplasia pathway, standardization of nomenclature, training of pathologists, and
      possibly development of ancillary techniques are of paramount importance for
      accurate patient management.

PMID- 17509992
TI  - Urine cytology discrepancies: frequency, causes, and outcomes.
AB  - Although urine cytology is used for the early detection and surveillance of
      urothelial carcinoma, there has been little study of the frequency, causes, and
      outcomes of cytologic-histologic discrepancies. We obtained histologic follow-up
      in 361 (6.2%) of 5,785 voided, 124 (19.5%) of 636 lower tract instrumented, and
      23 (33%) of 69 upper tract urinary cytologic specimens from 1 institution during
      a 2-year timeframe to determine diagnostic discrepancy frequency and outcomes.
      Cytologic-histologic discrepancies were observed in 208 (40.9%) cases with
      histologic followup, and the cause of discrepancy was interpretation and sampling
      in 35.1% and 63.0%, respectively. Of all discrepancies, 101 (48.6%) resulted in
      minimal or mild harm, consisting mainly of repeated testing and/or diagnostic
      delays. Severe harm never was observed. We conclude that current screening and
      surveillance methods that incorporate urine cytology are accurate in diagnosing
      urothelial cancer. However, the current protocols result in potentially reducible
      errors that lead to unnecessary testing and diagnostic delays.

PMID- 17509993
TI  - Correlation of serum TNF-alpha levels and histologic liver injury scores in
      pediatric nonalcoholic fatty liver disease.
AB  - We tested the power of tumor necrosis factor (TNF)-alpha and/or leptin in
      predicting the degree of liver involvement in children with nonalcoholic fatty
      liver disease (NAFLD). We measured serum levels of TNF-alpha and leptin and
      computed NAFLD activity score (NAS) (NAS >or= 5, diagnostic of nonalcoholic
      steatohepatitis [NASH]) in 72 consecutive biopsy-proven NAFLD cases (training and
      validation sets, 36 cases each). Univariate analysis evaluated variables
      significantly associated with a diagnostic NAS. Receiver operating characteristic
      (ROC) curve analysis assessed the diagnostic value of selected variables in
      predicting a NAS of 5 or more.TNF-alpha (P < .0001), leptin (P = .001);
      triglycerides (P = .013), and alkaline phosphatase (P = .046) levels were
      significantly associated with a NAS of 5 or more. TNF-alpha and leptin levels
      predicted the risk of NAS of 5 or more. ROC analyses defined cutoff values for
      TNF-alpha, leptin, and risk score. They identified 90%, 83%, and 83% of the
      cases, respectively, with a NAS of 5 or more (true-positive cases) from the
      validation set.TNF-alpha alone or combined with leptin in a simple risk score can
      accurately predict a NAS of 5 or more. TNF-alpha seems to be a specific
      laboratory marker of NASH.

PMID- 17509994
TI  - Recommended curriculum for teaching hematopathology to subspecialty
      hematopathology fellows.
AB  - The performance and interpretation of clinical hematology and hematopathology
      laboratory tests and diagnosis of benign or malignant hematolymphoid disorders
      present unique challenges to hematopathology fellow trainees. To assist
      hematopathology fellowship program directors in preparing trainees to meet these
      challenges, a task force of pathologists with expertise in hematopathology
      developed a suggested training curriculum that includes a comprehensive list of
      topics in the areas of analytic hematology, bone marrow pathology, lymph node
      pathology, splenic pathology, lymphoma diagnostics, cytogenetics, and molecular
      diagnostics. This report also includes recommendations for training experiences
      that will facilitate the transition of subspecialty residents to practicing
      consultants in hematopathology.

PMID- 17509995
TI  - A simple, rapid, and sensitive method for the detection of the JAK2 V617F
      mutation.
AB  - The point mutation 1849 (GT) V617F in the JAK2 gene occurs at high frequency in
      several chronic myeloproliferative diseases. Although a number of V617F mutation
      detection methods have been described, few are readily implemented in a
      diagnostic setting. We developed a simple and sensitive allelespecific
      competitive blocker polymerase chain reaction (ACB-PCR) assay to detect the V617F
      mutation. DNA was extracted from peripheral whole blood samples of 26 patients
      with chronic myeloproliferative disease. The ACB-PCR limit of detection was 1%.
      All positive samples detected by sequencing were detected by ACB-PCR. In 3
      patients with essential thrombocythemia, the V617F mutation was readily detected
      by ACB-PCR but was near the detection limit of sequencing, confirming that ACB
      PCR is more effective at detecting V617F when the mutant cell population is low.
      Detection of the monomorphic JAK2 V617F mutation using the ACB-PCR assay is easy
      to perform, rapid, sensitive, and cost-effective, which are key features of an
      ideal diagnostic method.

PMID- 17509996
TI  - Otc product: plan B emergency contraception.

PMID- 17509999
TI  - Pharmacoepidemiology of potential alcohol-prescription drug interactions among
      primary care patients with alcohol-use disorders.
AB  - OBJECTIVE: To report on the proportion of individuals with alcohol-use disorders
      who take prescription medications that could interact with alcohol and on the
      proportion who recall advice to avoid alcohol with their medications. DESIGN:
      Secondary analysis of a randomized controlled trial of telephone counseling.
      SETTING: 18 primary care practices in south-central and southeastern Wisconsin.
      PATIENTS: 897 adults with alcohol-use disorders as identified by systematic
      survey. INTERVENTION: Telephone and mail survey. MAIN OUTCOME MEASURES: Patient
      reported prescription medication use, potential for alcohol-drug interactions
      according to DrugDex, and patient-reported receipt of advice not to take alcohol
      with their medications. RESULTS: Of the 869 patients who provided usable
      information on prescription medication use, 348 (40.0%) were taking medications
      with alcohol interactions or proscriptions; the most frequently reported were
      bupropion, selective serotonin reuptake inhibitors, and various acetaminophen
      containing compounds. Slightly more than 20% of patients were taking medications
      with moderate to severe alcohol interactions; over one-third of these 184
      patients did not recall advice to avoid alcohol. CONCLUSION: Practitioners who
      prescribe or dispense medications may need to enhance their efforts to advise
      patients about alcohol-drug interactions. Prescribing and dispensing medications
      that interact with alcohol present opportunities to administer alcohol screens
      and interventions.

PMID- 17510000
TI  - Therapeutic rationale of combining therapy with gemfibrozil and simvastatin.
AB  - OBJECTIVES: To examine specific indications for patients receiving therapy with
      gemfibrozil plus simvastatin at doses of more than 10 mg daily and determine
      whether these patient-specific indications met Adult Treatment Panel (ATP) III
      criteria for combination therapy; and secondarily to identify any complications
      occurring between August 30, 2002, and May 1, 2003. DESIGN: Retrospective cohort
      study. SETTING: Tertiary care, university-affiliated, Southern Arizona Veterans
      Affairs Healthcare System from August 30, 2002, to May 1, 2003. PATIENTS: 80
      patients with active prescriptions for gemfibrozil at any dose and simvastatin at
      doses of more than 10 mg daily as of August 30, 2002; and 23 patients who had
      been prescribed this drug at other institutions. INTERVENTION: Retrospective
      chart review. MAIN OUTCOME MEASURES: Frequency of meeting ATP III criteria for
      combination therapy with gemfibrozil and simvastatin was the primary outcome
      measure (primary). RESULTS: Of the 80 patients, 45 (56%) met ATP III guidelines
      for combination therapy. Among the 80 patients started on these drugs at this VA
      facility, gemfibrozil was added to simvastatin in 61 patients, simvastatin was
      added to gemfibrozil in 18, and the agents were begun simultaneously for 1
      patient. Common errors included combination treatment when LDL cholesterol values
      could not be calculated (because of serum triglycerides levels exceeding 400
      mg/dL); use of gemfibrozil at triglyceride levels lower than the 500 mg/dL with
      attainment of non-HDL goals; and use of gemfibrozil when triglyceride levels were
      not measured. One death secondary to rhabdomyolysis occurred in a patient whose
      care did not meet ATP III guidelines. CONCLUSION: Combination therapy with
      simvastatin and gemfibrozil often did not meet ATP III standards. A higher risk
      of serious adverse events results from combining these drugs, and systems to
      improve adherence to guidelines may improve the safety of treating dyslipidemic
      patients.

PMID- 17510001
TI  - Impact of an asthma-specific questionnaire on problem identification and clinical
      and economic outcomes in ambulatory patients with persistent asthma.
AB  - OBJECTIVE: To determine the impact of an asthma-specific questionnaire on problem
      identification and patient outcomes. DESIGN: Prospective, two-group, parallel,
      randomized, multisite study. SETTING: Conducted at 10 community pharmacies in
      suburban Detroit from January 2000 to April 2003. PATIENTS: 60 adult and
      pediatric patients with persistent asthma receiving daily medication.
      INTERVENTION: A 17-item questionnaire designed to query understanding of and
      response to therapy and confidence in asthma prevention and treatment was
      completed by all participants at routine visits. Pharmacists reviewed
      questionnaire results with 31 intervention (group 1) participants during a 5- to
      10-minute interaction, while 29 control (group 2) participants received standard
      care only. MAIN OUTCOME MEASURES: Number and type of problems identified.
      Secondary outcomes were use of clinical outcomes, resource utilization, drug use
      and understanding, missed school or work days, and participant confidence.
      RESULTS: Group 1 and group 2 participants were monitored for a mean of 5.4 and
      5.2 months, respectively. Overall, 68 problems were identified in group 1 and 4
      in group 2. Confidence in preventing asthma episodes improved 29% and confidence
      in treating symptomatic episodes improved 10% in group 1 participants, whereas
      there were no improvements in group 2. Symptom frequency, rescue drug use,
      restricted activity, and patients with more than two nocturnal episodes per month
      decreased within both groups. There were low incidences of and no statistically
      significant group differences for frequency of oral steroids, resource use, and
      missed school or work days. Likewise, group differences in drug use and
      understanding were not significant. CONCLUSION: The questionnaire aided
      pharmacists in problem identification and may be useful in a busy pharmacy. Study
      limitations such as small sample size, short follow-up period, and liberal
      enrollment contributed to the lack of group differences in our secondary
      outcomes. Future studies need to address our study limitations and explore
      additional practical methods of providing pharmaceutical care in the community
      pharmacy setting.

PMID- 17510002
TI  - Weight and blood pressure changes after switching second-generation
      antipsychotics in a population of veterans with schizophrenia-related disorders.
AB  - OBJECTIVES: To describe (1) the association between systolic blood pressure (SBP)
      and diastolic blood pressure (DBP) changes and weight change and (2) weight, SBP,
      and DBP changes attributable to the medication following a switch from one second
      generation antipsychotic (SGA) to another. DESIGN: Retrospective, naturalistic,
      nonequivalent control group study. SETTING: United States between April 1, 2002,
      and September 30, 2002. PATIENTS: 1,425 U.S. Veterans Healthcare System enrollees
      with diagnoses of schizophrenia or schizoaffective disorders. INTERVENTION:
      Analysis of data from the Veterans Integrated System Technology Architecture.
      MAIN OUTCOME MEASURES: Veterans' weight, SBP, and DBP. RESULTS: Weight change and
      change in SBP (r = 0.19) and DBP (r = 0.15) were significant (P < 0.001), even
      after adjusting for obesity status (body mass index <30 or > or = 30 kg/m2).
      Veterans who were switched from olanzapine to another SGA lost weight (P <
      0.001), whereas those switched from another SGA to olanzapine gained weight (P <
      0.05). Weight change remained significant after controlling for preswitch obesity
      status (P < 0.001). Blood pressure was not associated with switch type after
      adjusting for preswitch obesity status. CONCLUSION: Monitoring and aggressively
      treating weight change is an evidence-based and relatively inexpensive strategy
      that primary care practitioners and psychiatrists can use in working in tandem
      toward reducing the already greater cardiovascular risk of patients with
      schizophrenia.

PMID- 17510003
TI  - Should I stay or should I go? The influence of individual and organizational
      factors on pharmacists' future work plans.
AB  - OBJECTIVES: To examine the association between individual (demographic) and
      organizational (work environment and workload) factors and pharmacists' future
      work plans and explore reasons for either leaving or staying with current
      employers (culture/climate factors). DESIGN: Cross-sectional study. SETTING:
      United States in 2004. PARTICIPANTS: 1,263 pharmacists. INTERVENTION: Seven-page
      mail survey. MAIN OUTCOME MEASURES: Future work plans, time spent in practice
      activities, staffing levels, and actual and perceived workload and demographic
      variables. RESULTS: Overall, 15% of respondents reported that they planned to
      leave their current employer within the year subsequent to this survey. More than
      50% reported that their workload had significantly increased in the previous
      year. Multivariate analyses showed that nonwhites were 2.1 times more likely to
      be planning to leave their current employer, compared with whites, and unmarried
      respondents were 1.7 times more likely to leave than were married individuals.
      More negative perceptions regarding the impact of workload on various personal,
      work, and patient care outcomes predicted leaving. A main factor that prompted
      their inclinations was described by 72% of leavers (insufficient and/or
      unqualified staff) and 49% of stayers (flexible scheduling). The most common
      reasons for staying were good salary and relationships with coworkers, while the
      most common reasons for leaving were a desire for change and stress/workload
      issues. CONCLUSION: Future work plans of pharmacists are influenced by a variety
      of individual, organizational, and culture/climate factors. While employers have
      little latitude for influencing demographic characteristics of employees, many
      organizational and culture/climate factors (scheduling, opportunities for
      interpersonal interactions, salary/benefits, staffing, and workload) can be
      addressed with the intent of reducing pharmacist turnover.

PMID- 17510004
TI  - Attitudes and interests of pharmacists regarding independent pharmacy ownership.
AB  - OBJECTIVE: To examine the beliefs, attitudes, and interests of Texas pharmacists
      at different career stages with respect to independent pharmacy ownership.
      DESIGN: Non-experimental, cross-sectional study. SETTING: Texas in November
      December 2004. PARTICIPANTS: 180 practicing pharmacists. INTERVENTION: Mail
      survey. MAIN OUTCOME MEASURES: Pharmacists' self-reported attitudes (ranging from
      -90, unfavorable, to +90, favorable) about and interest (-3, very unlikely, to
      +3, very likely) in independent pharmacy ownership. RESULTS: Pharmacists reported
      an overall favorable attitude toward independent pharmacy ownership (mean [+/-
      SD] 18.6 +/- 28, range -63.0 to 90.0). Beliefs that ownership would increase
      their business autonomy, professional autonomy, and ability to establish patient
      loyalty made the largest contributions to overall attitude. Pharmacists'
      attitudes toward ownership differed by career stage (F = 3.12, df = 2, P =
      0.047), with middle- (age 36-49 years) and early- (age < or = 35 years) career
      stage pharmacists reporting the most and least favorable attitudes, respectively.
      Pharmacists reported a low interest in pursuing ownership (-2.2 +/- 1.6, -3.0 to
      +3.0). Financial rewards (r = 0.26, P < 0.001) and the need for
      business/managerial skills (r = 0.25, P < 0.001) were most highly correlated with
      pharmacists' interest in pursuing ownership. Multivariate findings indicated that
      pharmacists with a higher interest in pursuing ownership and those with advanced
      training certifications had significantly more favorable attitudes toward
      ownership than their counterparts. In addition, interest in pursuing pharmacy
      ownership was higher in pharmacists who offered compounding services, could
      obtain financial resources, practiced in rural locations, and had more favorable
      attitudes toward ownership. CONCLUSION: Overall, pharmacists indicated favorable
      attitudes toward independent pharmacy ownership but low interest in pursuing
      ownership. Their attitudes differed based on career stage, and more favorable
      attitudes--grounded especially in beliefs about autonomy and patient loyalty-
      were associated with a greater interest in ownership. Strategies to stimulate
      pharmacy ownership should be varied and targeted to influence beliefs that are
      driving pharmacists' attitudes at various career stages.

PMID- 17510005
TI  - Self-reported medication errors among employees of a pharmaceutical company and
      their families.

PMID- 17510006
TI  - Evaluation of a novel tablet splitter.

PMID- 17510007
TI  - Clinical and cost-saving interventions performed by pharmacists in a community
      health clinic pharmacy.

PMID- 17510008
TI  - Addressing the pharmacist shortage through a cooperative internship program for
      foreign pharmacy graduates.
AB  - OBJECTIVE: To describe the Latin American Pharmacist Internship Program, a pilot
      project to prepare foreign-trained pharmacists for pharmacy licensure in the
      United States. SETTING: Two schools of pharmacy (located in Arequipa, Peru, and
      Boston, Mass.) and a chain pharmacy in the Greater Boston area. PRACTICE
      DESCRIPTION: Didactic/experiential pharmacy completion program. PRACTICE
      INNOVATION/INTERVENTIONS: Three distinct phases combining didactic courses
      delivered at two schools of pharmacy with supervised experiential training in a
      community pharmacy setting. MAIN OUTCOME MEASURE: Completion of the program
      requirements for licensure in the United States within 1 year by 15 licensed
      Peruvian pharmacists who participated in a pilot project. RESULTS: As of June 30,
      2006, nine interns from the original group had received a pharmacy license in the
      United States and one was awaiting results of the North American Pharmacist
      Licensure Examination. Three returned to Peru, and two continued to work as
      pharmacy interns while working toward completion of the requirements for
      licensure. CONCLUSION: For the Latin American Pharmacist Internship Program to be
      successful, these results show that the following components should be
      incorporated: (1) admission criteria should include a Test of English as a
      Foreign Language score of 550 or more and a Test of Spoken English score of 50 or
      more (or the equivalent Internet-based Test scores required by National
      Association of Boards of Pharmacy), (2) admission should be open to all qualified
      candidates from around the world, (3) the program's timeline for completion
      should be extended to 18 months, (4) interns should receive more instruction in
      assertiveness and U.S. employment practices, and (5) preceptors should receive
      additional training in culturally sensitive supervisory techniques.

PMID- 17510009
TI  - Believe in the beauty of your dreams: a message to new pharmacy graduates.
AB  - OBJECTIVE: To encourage new pharmacy graduates who enter community practice to
      adopt three approaches to life that will bring them personal and professional
      fulfillment. DATA SOURCES: Published evidence on adverse drug events (ADEs),
      surveys of the community pharmacy work environment, and observations on how most
      pharmacists spend their time. SUMMARY: New pharmacy graduates are encouraged to
      continue their "education in the classroom of life," deepen their awareness of
      the dimensions of human potential, and apply their ever-expanding wisdom to the
      advancement of pharmacy. Estimates indicate that 15 patients per day will
      experience some harm or less-than-optimal result from the medicines dispensed by
      a community pharmacist. About one-fourth of ADEs are preventable; therefore, an
      opportunity exists for community pharmacists to help patients avoid the pain,
      distress, or expense of an ADE. Community pharmacists should demonstrate more
      awareness of this situation and resolve to help correct it. Five actions are
      suggested that, if taken by enough pharmacists over sufficient time, would close
      the current gap between the capabilities of pharmacists and their influence on
      the safe and appropriate use of medicines. CONCLUSION: Pharmacists have many
      choices in their professional practice, and more should assertively endeavor to
      practice in ways that help people achieve optimum wellness through appropriate
      use of medicines.

PMID- 17510011
TI  - Justin Lawrence Powers (1895-1981): champion of improved medication standards.

PMID- 17510012
TI  - Vaccine schedules: revisions for 2007.

PMID- 17510013
TI  - New drugs: paliperidone, dasatinib, and decitabine.

PMID- 17510014
TI  - Otc product: citracal creamy bites.

PMID- 17510015
TI  - Generic Darwinian selection in catalytic protocell assemblies.
AB  - To satisfy the minimal requirements for life, an information carrying molecular
      structure must be able to convert resources into building blocks and also be able
      to adapt to or modify its environment to enhance its own proliferation.
      Furthermore, new copies of itself must have variable fitness such that evolution
      is possible. In practical terms, a minimal protocell should be characterized by a
      strong coupling between its metabolism and genetic subsystem, which is made
      possible by the container. There is still no general agreement on how such a
      complex system might have been naturally selected for in a prebiotic environment.
      However, the historical details are not important for our investigations as they
      are related to assembling and evolution of protocells in the laboratory. Here, we
      study three different minimal protocell models of increasing complexity, all of
      them incorporating the coupling between a 'genetic template', a container and,
      eventually, a toy metabolism. We show that for any local growth law associated
      with template self-replication, the overall temporal evolution of all protocell's
      components follows an exponential growth (efficient or uninhibited
      autocatalysis). Thus, such a system attains exponential growth through
      coordinated catalytic growth of its component subsystems, independent of the
      replication efficiency of the involved subsystems. As exponential growth implies
      the survival of the fittest in a competitive environment, these results suggest
      that protocell assemblies could be efficient vehicles in terms of evolving
      through Darwinian selection.

PMID- 17510016
TI  - The rate of metabolism in marine animals: environmental constraints, ecological
      demands and energetic opportunities.
AB  - The rates of metabolism in animals vary tremendously throughout the biosphere.
      The origins of this variation are a matter of active debate with some scientists
      highlighting the importance of anatomical or environmental constraints, while
      others emphasize the diversity of ecological roles that organisms play and the
      associated energy demands. Here, we analyse metabolic rates in diverse marine
      taxa, with special emphasis on patterns of metabolic rate across a depth
      gradient, in an effort to understand the extent and underlying causes of
      variation. The conclusion from this analysis is that low rates of metabolism, in
      the deep sea and elsewhere, do not result from resource (e.g. food or oxygen)
      limitation or from temperature or pressure constraint. While metabolic rates do
      decline strongly with depth in several important animal groups, for others
      metabolism in abyssal species proceeds as fast as in ecologically similar shallow
      water species at equivalent temperatures. Rather, high metabolic demand follows
      strong selection for locomotory capacity among visual predators inhabiting well
      lit oceanic waters. Relaxation of this selection where visual predation is
      limited provides an opportunity for reduced energy expenditure. Large-scale
      metabolic variation in the ocean results from interspecific differences in
      ecological energy demand.

PMID- 17510017
TI  - A minimal and self-consistent in silico cell model based on macromolecular
      interactions.
AB  - A self-consistent minimal cell model with a physically motivated schema for
      molecular interaction is introduced and described. The genetic and metabolic
      reaction network of the cell is modelled by multidimensional nonlinear ordinary
      differential equations, which are derived from biochemical kinetics. The strategy
      behind this modelling approach is to keep the model sufficiently simple in order
      to be able to perform studies on evolutionary optimization in populations of
      cells. At the same time, the model should be complex enough to handle the basic
      features of genetic control of metabolism and coupling to environmental factors.
      Thereby, the model system will provide insight into the mechanisms leading to
      important biological phenomena, such as homeostasis, (circadian) rhythms,
      robustness and adaptation to a changing environment. One example of modelling a
      molecular regulatory mechanism, cooperative binding of transcription factors, is
      discussed in detail.

PMID- 17510018
TI  - Synthetic Turing protocells: vesicle self-reproduction through symmetry-breaking
      instabilities.
AB  - The reproduction of a living cell requires a repeatable set of chemical events to
      be properly coordinated. Such events define a replication cycle, coupling the
      growth and shape change of the cell membrane with internal metabolic reactions.
      Although the logic of such process is determined by potentially simple physico
      chemical laws, modelling of a full, self-maintained cell cycle is not trivial.
      Here we present a novel approach to the problem that makes use of so-called
      symmetry breaking instabilities as the engine of cell growth and division. It is
      shown that the process occurs as a consequence of the breaking of spatial
      symmetry and provides a reliable mechanism of vesicle growth and reproduction.
      Our model opens the possibility of a synthetic protocell lacking information but
      displaying self-reproduction under a very simple set of chemical reactions.

PMID- 17510019
TI  - Coevolution of compositional protocells and their environment.
AB  - The coevolution of environment and living organisms is well known in nature.
      Here, it is suggested that similar processes can take place before the onset of
      life, where protocellular entities, rather than full-fledged living systems,
      coevolve along with their surroundings. Specifically, it is suggested that the
      chemical composition of the environment may have governed the chemical repertoire
      generated within molecular assemblies, compositional protocells, while compounds
      generated within these protocells altered the chemical composition of the
      environment. We present an extension of the graded autocatalysis replication
      domain (GARD) model--the environment exchange polymer GARD (EE-GARD) model. In
      the new model, molecules, which are formed in a protocellular assembly, may be
      exported to the environment that surrounds the protocell. Computer simulations of
      the model using an infinite-sized environment showed that EE-GARD assemblies may
      assume several distinct quasi-stationary compositions (composomes), similar to
      the observations in previous variants of the GARD model. A statistical analysis
      suggested that the repertoire of composomes manifested by the assemblies is
      independent of time. In simulations with a finite environment, this was not the
      case. Composomes, which were frequent in the early stages of the simulation
      disappeared, while others emerged. The change in the frequencies of composomes
      was found to be correlated with changes induced on the environment by the
      assembly. The EE-GARD model is the first GARD model to portray a possible time
      evolution of the composomes repertoire.

PMID- 17510020
TI  - Minimal model of self-replicating nanocells: a physically embodied information
      free scenario.
AB  - The building of minimal self-reproducing systems with a physical embodiment
      (generically called protocells) is a great challenge, with implications for both
      theory and applied sciences. Although the classical view of a living protocell
      assumes that it includes information-carrying molecules as an essential
      ingredient, a dividing cell-like structure can be built from a metabolism
      container coupled system only. An example of such a system, modelled with
      dissipative particle dynamics, is presented here. This article demonstrates how a
      simple coupling between a precursor molecule and surfactant molecules forming
      micelles can experience a growth-division cycle in a predictable manner, and
      analyses the influence of crucial parameters on this replication cycle.
      Implications of these results for origins of cellular life and living technology
      are outlined.

PMID- 17510021
TI  - Stochastic simulations of minimal self-reproducing cellular systems.
AB  - This paper is a theoretical attempt to gain insight into the problem of how self
      assembling vesicles (closed bilayer structures) could progressively turn into
      minimal self-producing and self-reproducing cells, i.e. into interesting
      candidates for (proto)biological systems. With this aim, we make use of a
      recently developed object-oriented platform to carry out stochastic simulations
      of chemical reaction networks that take place in dynamic cellular compartments.
      We apply this new tool to study the behaviour of different minimal cell models,
      making realistic assumptions about the physico-chemical processes and conditions
      involved (e.g. thermodynamic equilibrium/non-equilibrium, variable volume-to
      surface relationship, osmotic pressure, solute diffusion across the membrane due
      to concentration gradients, buffering effect). The new programming platform has
      been designed to analyse not only how a single protometabolic cell could maintain
      itself, grow or divide, but also how a collection of these cells could 'evolve'
      as a result of their mutual interactions in a common environment.

PMID- 17510022
TI  - Structural analyses of a hypothetical minimal metabolism.
AB  - By integrating data from comparative genomics and large-scale deletion studies,
      we previously proposed a minimal gene set comprising 206 protein-coding genes. To
      evaluate the consistency of the metabolism encoded by such a minimal genome, we
      have carried out a series of computational analyses. Firstly, the topology of the
      minimal metabolism was compared with that of the reconstructed networks from
      natural bacterial genomes. Secondly, the robustness of the metabolic network was
      evaluated by simulated mutagenesis and, finally, the stoichiometric consistency
      was assessed by automatically deriving the steady-state solutions from the
      reaction set. The results indicated that the proposed minimal metabolism presents
      stoichiometric consistency and that it is organized as a complex power-law
      network with topological parameters falling within the expected range for a
      natural metabolism of its size. The robustness analyses revealed that most random
      mutations do not alter the topology of the network significantly, but do cause
      significant damage by preventing the synthesis of several compounds or
      compromising the stoichiometric consistency of the metabolism. The implications
      that these results have on the origins of metabolic complexity and the
      theoretical design of an artificial minimal cell are discussed.

PMID- 17510023
TI  - OTC product: MiraLAX.

PMID- 17510025
TI  - Adverse effects associated with OTC ceruminolytics and ear irrigation.

PMID- 17510027
TI  - Impact of drug importation on community pharmacy and patient care.

PMID- 17510028
TI  - Prescription drug product substitution decision support.
AB  - OBJECTIVE: To generate patient-centered, evidence-based decision support tools
      and compile resources that will assist pharmacists in prescription drug product
      substitution activities and related communication, and to present the resulting
      tools and resources. DATA SOURCES: Food and Drug Administration (FDA)
      publications, data, and communication; peer-reviewed literature; interviews with
      pharmacists; structured discussions with members of the project Advisory Board;
      and author's own knowledge and records of events. SUMMARY: A decision whether to
      substitute an alternative product for a prescribed medication is a clinically
      based process that must be grounded in appropriate medical evidence, therapeutic
      equivalence information, financial factors, and consideration of how the
      substitution will impact the patient. Product substitution decisions are
      influenced by therapeutic issues, legal matters, patient-centered concerns, and
      pharmacy practice factors, including work flow, supply issues, access to current
      resources, and misperceptions about database information. While generic
      substitution is clearly defined in many cases, some medication categories require
      special consideration, i.e., critical dose and narrow therapeutic index drugs,
      products with special release mechanisms, bioengineered protein products, many
      hormonal products, older drugs marketed before 1938 that were not subject to FDA
      approval, and others with limited bioequivalence data. In response to reports of
      the challenges pharmacists face when determining the appropriateness of product
      substitution and in support of their interdisciplinary efforts to improve
      medication use, the American Pharmacists Association (APhA) convened an advisory
      board to create the decision support tool featured in this article. CONCLUSION:
      The U.S. health care system and patients rely on pharmacists as medication use
      experts to ensure that prescription drug product substitutions are appropriate.
      Pharmacists must be able to efficiently determine therapeutic equivalence,
      identify situations where further research is required, have access to timely
      resources for gathering information, and effectively communicate with patients
      and physicians about substitution issues. The prescription drug product
      substitution tool and related resources presented are intended to assist
      pharmacists in making and communicating clinically sound product substitution
      decisions that are patient centered, evidence based, consistent with state and
      federal laws and regulations, and reflective of the realities of health care
      today.

PMID- 17510029
TI  - Examination of state-level changes in the pharmacist labor market using Census
      data.
AB  - OBJECTIVE: To examine long-term changes in the U.S. pharmacist labor market
      across states. DESIGN: Retrospective cohort study. SETTING: The United States as
      a whole and individual states in 1990 and 2000. PARTICIPANTS: Pharmacists and
      pharmacy school graduates from Census data and previous research, respectively.
      INTERVENTION: Retrospective analysis of 5% Public Use Microdata Samples data on
      pharmacists from the 1990 and 2000 U.S. Census surveys, information on migration
      among states between 1995 and 2000, and previous research on pharmacy school
      graduates. MAIN OUTCOME MEASURES: Changes in pharmacist counts and wages, as well
      as migration of pharmacists across states and pharmacy school graduates by state.
      RESULTS: From 1990 to 2000, the ratio of pharmacists to 100,000 population
      increased from 70 to 76, but 13 states experienced declines in this datum, and
      overall changes in pharmacist counts varied considerably among states. The
      average wage, expressed in 2000 U.S. dollars, for pharmacists increased from
      $26.58 per hour to $33.80 per hour (17%), while the average wages of non
      pharmacist college graduates increased from $26.37 to only $28.76 (9%). Wage
      changes varied across states. CONCLUSION: According to the Census, the number of
      pharmacists per 100,000 population varied substantially across states. This
      variance in supply across states is not converging or easily explained. Overall,
      the shortage had a clear impact on the pharmacist labor market, yet this effect
      was not consistent across states.

PMID- 17510030
TI  - Impact of pharmacy care services on patients' perceptions of health care quality
      for diabetes.
AB  - OBJECTIVES: To (1) construct and evaluate a measure of patients' perceptions of
      the quality of diabetes care and (2) determine the impact of pharmacy care
      services (PCSs) on patients' perceptions of the quality of their diabetes care
      while controlling for patient-related factors. DESIGN: Two-phased study using a
      single-group, pretest-posttest design. SETTING: Community pharmacies that
      provided PCSs to diabetic patients as part of the Patient Self-Management Program
      for Diabetes in North Carolina, Georgia, Ohio, and Wisconsin. PARTICIPANTS: 218
      patients with diabetes covered by self-insured employers' health plans.
      INTERVENTIONS: Pharmacist-provided care services using scheduled consultations,
      clinical goal setting, monitoring, and collaborative drug therapy management with
      physicians and referrals to diabetes educators. MAIN OUTCOMES MEASURES: Changes
      in patients' perceptions of quality measured by a self-administered questionnaire
      that included a six-item scale of information quality, a five-item scale of
      provider quality, and a one-item overall rating of care. RESULTS: The assessment
      of the baseline data (Phase I) demonstrated that the measures of perceived
      quality possessed acceptable psychometric properties. After PCSs were implemented
      (Phase II), the scores for the information scale improved significantly (paired t
      = 7.64, P < 0.01), as did the scores for the provider scale (paired t = 6.30, P <
      0.01) and the overall rating (paired t = 5.54, P < 0.01). In multivariate
      analyses, the improvement in perceived quality was not explained by the change in
      glycosylated hemoglobin when controlling for age, gender, race/ethnicity, and
      baseline quality perceptions. CONCLUSION: PCSs enhanced patients' perceived
      quality of their diabetes care. The improvement in perceived quality was not
      explained by the change in glycemic control, which suggests that nonclinical
      factors in care are important to patients' evaluations of quality.

PMID- 17510031
TI  - Drug sample provision and its effect on continuous drug therapy in an indigent
      care setting.
AB  - OBJECTIVE: To assess the continuity and consistency of drug therapy among
      indigent patients following drug sample provision. DESIGN: Retrospective study.
      SETTING: Indigent ambulatory care. PATIENTS: 129 adult patients, identified as
      having been given a drug sample between January 1, 2004, and February 27, 2004.
      INTERVENTIONS: Analysis of data regarding the sample regimen, duration, rationale
      for sample provision, therapeutic indication, and subsequent therapy prescribed
      in the 6 months following sample provision. MAIN OUTCOME MEASURES: Lengths of
      gaps between sample provision and subsequent prescribed therapy were analyzed to
      evaluate the effect of sample provision on the continuity and consistency of drug
      therapy. RESULTS: Of the 52 patients for whom continuous therapy was indicated,
      interruptions in therapy occurred in 50% (mean duration, 51.1 +/- 37.8 days;
      range, 2-123). Of the 65 patients who were prescribed subsequent therapy, 89.2%
      were prescribed the exact same drug, 9.2% a different drug in the same class, and
      1.5% a different drug in a different class. Following sample provision, only 2
      (3.1%) patients were prescribed generic medications. CONCLUSION: Significant
      interruptions in drug therapy frequently followed sample provision in those
      requiring continuous treatment. On average, patients experienced interruptions in
      therapy for nearly 2 months. The majority of patients who were prescribed
      subsequent therapy were prescribed the same drug as the drug sample initially
      provided.

PMID- 17510032
TI  - Effect on lipid profiles of switching from olanzapine to another second
      generation antipsychotic agent in veterans with schizophrenia.
AB  - OBJECTIVE: To compare (1) mean low-density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C), and triglyceride differences after
      switching from olanzapine to quetiapine, risperidone, or ziprasidone and (2) the
      mean lipid change between switch patterns. DESIGN: Retrospective, naturalistic,
      nonequivalent control group design. SETTING: United States between April 1, 2002,
      and September 30, 2002. PATIENTS: 1,826 U.S. Veterans Healthcare System enrollees
      with diagnoses of schizophrenia or schizoaffective disorders and receiving a
      second-generation antipsychotic (SGA) medication. INTERVENTIONS: Analysis of data
      from the Veterans Information Systems and Technology Architecture. MAIN OUTCOME
      MEASURES: Differences in LDL-C, HDL-C, and triglycerides and mean differences
      between switch patterns. Predictors were the type of switch (e.g., olanzapine to
      quetiapine) and switch patterns (e.g., olanzapine to quetiapine versus olanzapine
      to risperidone). Data were analyzed using Pearson's X2 and multivariate analysis
      of covariance with planned comparisons. RESULTS: After adjusting for age, gender,
      and race/ethnicity, LDL-C decreased significantly among patients switched from
      olanzapine to ziprasidone (-16.9 mg/dL, P <0.01) and olanzapine to quetiapine (
      7.6 mg/dL, P = 0.04) and trended upward in patients switched from olanzapine to
      risperidone (+6.6 mg/dL, P = 0.12). Triglyceride levels decreased among those
      switched from olanzapine to ziprasidone (-62.9 mg/dL, P <0.01) and olanzapine to
      risperidone (-48.5 mg/dL, P <0.01) but not among veterans switched from
      olanzapine to quetiapine (+7.8 mg/dL, P = 0.54). HDL-C levels did not change
      significantly when veterans were switched from olanzapine to quetiapine,
      risperidone, or ziprasidone. CONCLUSION: Switching SGAs can increase or decrease
      cardiovascular risk depending on the clinician's follow-on SGA choice. LDL-C and
      triglyceride levels decreased significantly among veterans switched from
      olanzapine to ziprasidone. Switching to quetiapine was associated with a
      reduction in LDL-C, while switching to risperidone resulted in lower triglyceride
      levels. Clinicians should use these results when building a patient care plan
      that includes switching of SGAs.

PMID- 17510033
TI  - Attitudes and knowledge about pain among West Virginia pharmacists.

PMID- 17510034
TI  - Outcomes of a Medicare Part D education program.

PMID- 17510035
TI  - Campus-community pharmacy partnership to foster awareness and use of MedlinePlus.
AB  - OBJECTIVE: To determine the impact of a campus-community pharmacy partnership to
      foster awareness and use of National Library of Medicine (NLM) databases,
      including MedlinePlus, among minority populations. DESIGN: Uncontrolled study
      with pretest and posttest. SETTING: Two community pharmacies and Bethel World
      Ministry in the Washington, D.C., metropolitan area. PARTICIPANTS: 8 student
      pharmacists and pharmacy residents and 92 patients. INTERVENTION: Training of
      patients by student pharmacists and pharmacy residents in the use of NLM
      databases during prescription-fill wait time. MAIN OUTCOME MEASURES: Pre- and
      post-survey responses and telephone followup designed to assess familiarity with
      NLM databases, including MedlinePlus. RESULTS: Overall, the familiarity of the
      participants with MedlinePlus and NLM databases increased fivefold before versus
      after training. The 1-week follow-up confirmed this trend. However, no
      statistically significant differences in responses (pre-and posttest/follow-up)
      to the surveys were observed in regard to specific questions on daily and future
      use of the NLM databases available on the Internet. CONCLUSION: Awareness and use
      of MedlinePlus by study participants increased.

PMID- 17510036
TI  - Development and implementation of a pharmacist-managed university-based wellness
      center.
AB  - OBJECTIVE: To describe the development and implementation of a pharmacist-managed
      wellness center based on campus within a school of pharmacy. SETTING: Duquesne
      University Mylan School of Pharmacy, located in Pittsburgh, Pa. PRACTICE
      DESCRIPTION: University-based employee wellness center, the Academic Research
      Center for Pharmacy Care, located within a school of pharmacy staffed by clinical
      practice faculty and student pharmacists. PRACTICE INNOVATION: The campus-based
      wellness practice integrates public health activities into the pharmacy school
      curriculum and provides a model that can be adapted for other ambulatory and
      community practices. INTERVENTIONS: Referral of clients to primary care providers
      following identification of risk for disease. MAIN OUTCOME MEASURES: Number of
      screenings; number of clients identified with elevated cholesterol, blood glucose
      (BG), blood pressure, or weight and referred to primary care providers; and
      number of student pharmacists participating in wellness experiential rotations.
      RESULTS: The center conducted more than 19,000 individual screenings on campus,
      in neighboring communities, and in the western Pennsylvania region from October
      2002 through May 2006. During the period July 2005 through May 2006, 16% of those
      screened required referral for elevated blood pressure (>140/90 mm Hg), 23%
      required referral for elevated total cholesterol (> 200 mg/dL, the population
      covers ages 20 to over 70 years), 8% required referral for elevated BG (fasting
      BG > or =100 mg/dL or nonfasting BG > or =200mg/dL), 43% required referral for
      low bone density (T-score < or =-1), 21% required referral for abnormal skin
      findings ranging from dryness to suspicious markings, and 26% required referral
      for body mass index (> or =30 kg/m2). A total of 70 student pharmacists, divided
      among two full-time clinical practice faculty, have participated in the wellness
      clinical rotation since 2004. CONCLUSION: Pharmacists can successfully direct
      public heath initiatives such as wellness and health promotion programs in an
      employee-based health center, in the community, and in community pharmacies.
      Pharmacists are able to identify primary preventive patients for referral to
      other health care providers.

PMID- 17510037
TI  - Bedlam Community Health Clinic: a collaborative interdisciplinary health care
      service for the medically indigent.
AB  - OBJECTIVE: To describe a collaborative interdisciplinary health care service
      delivery system for the medically indigent in the Tulsa and northeastern Oklahoma
      area independent of state or federal funding. SETTING: Northeastern Oklahoma and
      Tulsa. PRACTICE DESCRIPTION: Community and ambulatory care for indigent patients.
      PRACTICE INNOVATION: Bedlam Community Health Clinic (BCHC), which opened in
      August 2003, provides services to patients through partnerships among the health
      care disciplines of the University of Oklahoma College of Pharmacy, Nursing, and
      Medicine; is staffed by community physicians and pharmacists who volunteer their
      time and expertise; and is funded by the local community. MAIN OUTCOME MEASURES:
      Experiences and patients served. RESULTS: BCHC is a collaborative
      interdisciplinary clinic that addresses the needs of the medically indigent in
      Tulsa and northeastern Oklahoma. Conceived, developed, and funded by the local
      community, it does not depend on state or federal funding. A variety of services,
      both general medicine and specialty, are provided through BCHC. Since its opening
      in August 2003, the clinic has provided hands-on training for students from a
      variety of health care disciplines. The pharmacist-patient encounters provide
      helpful, meaningful drug information. The participation of volunteer pharmacists
      enables medically underserved or indigent patients to access pharmaceutical care
      and addresses the diverse health care needs of this often overlooked population.
      CONCLUSION: Health professionals and students in the Tulsa area have created an
      innovative mechanism for serving indigent patients who otherwise would lack
      adequate health care services.

PMID- 17510038
TI  - Role of student pharmacist interns in hospital-based standing orders pneumococcal
      vaccination program.
AB  - OBJECTIVE: To describe the role of student pharmacist interns in supporting a
      standing orders program (SOP) for pneumococcal polysaccharide vaccination in
      hospitalized patients. SETTING: University of Pittsburgh Medical Center (UPMC)
      Presbyterian, an academic teaching hospital in Pittsburgh. PRACTICE DESCRIPTION:
      The hospital-based Drug Use and Disease State Management (DUDSM) program designs,
      implements, and promotes evidence-based practice guidelines to ensure safe and
      cost-effective drug therapy. PRACTICE INNOVATION/INTERVENTIONS: Paid student
      pharmacist interns provide manpower for screening and maintaining the vaccination
      SOP. Student preparation includes classroom learning about immunization concepts,
      on-site SOP workflow training, and direct patient care activities. Students
      participate in the vaccination SOP by (1) screening daily admissions through
      computerized information systems, (2) reviewing databases for documented prior
      vaccination, (3) completing preprinted orders for pharmacists, (4) inserting
      orders into patient charts, (5) checking vaccine administration, (6) educating
      nurses, and (7) managing the databases. Pharmacists verify and sign vaccine
      orders. Nurses obtain patient history and consent and administer vaccines. MAIN
      OUTCOME MEASURES: Hospital vaccination rates as determined monthly for quality
      improvement reporting, and student time required to complete SOP functions.
      RESULTS: In 2005, an average monthly vaccination rate of 70% for hospitalized
      elderly was achieved by this inpatient SOP, with the highest rate (89%) occurring
      in March. On average, 800 patients were screened each month, with 480 vaccine
      orders placed into patient charts. CONCLUSION: A vaccination SOP is resource
      intensive and requires a diligent effort from qualified personnel. In our
      institution, trained student interns in the DUDSM program perform the necessary
      daily functions, such as patient screening, that are instrumental in maintaining
      the SOP.

PMID- 17510039
TI  - Professional implications of the expansion of pharmacy-based medical clinics.
AB  - OBJECTIVE: To describe challenges and opportunities to the profession of pharmacy
      associated with the emergence of pharmacy-based medical clinics. SUMMARY:
      Pharmacy-based medical clinics have emerged as a convenient, low-cost treatment
      option for many patients. These clinics, which are staffed by physicians'
      assistants or nurse practitioners, often are located directly within community
      pharmacies and offer rapid diagnosis and treatment for a limited number of health
      problems. With plans for significant expansion of these clinics, the profession
      of pharmacy faces a number of challenges. Allocating space in community
      pharmacies for medical clinics could place pharmacists at a disadvantage to other
      providers as they pursue ancillary health care activities. However, these clinics
      also represent an opportunity for pharmacists to position themselves as
      legitimized health care providers who are reimbursed for the consultative
      services they perform. Because most conditions diagnosed at pharmacy-based
      medical clinics have well-established treatment protocols, pharmacists would be
      well positioned to provide these services under collaborative practice
      agreements. This could ultimately provide the resources and payment structure
      necessary for pharmacists to provide other types of patient care services,
      including medication therapy management (MTM). CONCLUSION: As pharmacy-based
      clinics continue to proliferate, pharmacists should carefully consider
      surrendering space in community pharmacies to other health care practitioners.
      These clinics present pharmacists with an opportunity to provide many of the
      additional health care services for which we have so vigorously argued. Failure
      to respond to the acute care needs of patients today may present pharmacists with
      a significant barrier as they continue to expand into direct patient care
      activities.

PMID- 17510040
TI  - Hugo Herman Schaefer (1891-1967): pharmacy's volunteer.

PMID- 17510041
TI  - Proper immunization technique: an update on current guidelines and
      recommendations.

PMID- 17510042
TI  - New drugs: aliskiren hemifumarate, lisdexamfetamine dimesylate, and lapatinib.

PMID- 17510043
TI  - OTC product: Gas-X Thin Strips.

PMID- 17510044
TI  - Anaesthesia for spinal surgery in children.
AB  - Spinal surgery is performed in children of all age groups. Some of these children
      will have significant, other medical problems. For most, surgery will be
      performed in the prone position. Blood loss may be high for some types of
      surgery, and patients will benefit from use of a blood-sparing technique. Many
      patients will require spinal cord monitoring to assess cord function and to
      prevent neurological deficit.

PMID- 17510045
TI  - The effect of ephedrine on intubating conditions and haemodynamics during rapid
      tracheal intubation using propofol and rocuronium.
AB  - BACKGROUND: We compared the effect of pre-treatment with ephedrine 75, 100, 150
      microg kg(-1) and saline on intubating conditions and haemodynamics during rapid
      tracheal intubation using propofol and rocuronium. METHODS: One hundred adult
      patients randomized into one of the four groups-PE 75, PE 100, PE 150, and saline
      (control) groups-were pre-treated with i.v. ephedrine 75, 100, 150 microg kg(-1)
      or saline, respectively, 1 min before rapid tracheal intubation using propofol
      2.5 mg kg(-1) and rocuronium 0.6 mg kg(-1). A blinded anaesthesiologist assessed
      the intubating conditions. Heart rate and mean arterial pressure were recorded
      before anaesthesia induction (baseline), post-induction, and every minute after
      intubation for 5 min. A 20% change in haemodynamic variables from baseline was
      regarded as clinically significant. Data were analysed using anova test with post
      hoc Tukey's test and chi2 or Fisher's exact test. P < 0.05 was regarded as
      significant. RESULTS: Patient characteristics, baseline heart rate, and mean
      arterial pressure were comparable between the groups. Intubating conditions were
      significantly better in the PE 75 (P = 0.003) and PE 100 (P = 0.001) groups. A
      significant increase in heart rate was observed in the PE 75 and PE 150 groups
      when compared with the saline group. A statistically significant difference in
      mean arterial pressure was noted between PE 75 and PE 150 groups and between PE
      150 and saline groups at most of the time intervals. However, when considering
      the clinical significance of these, all groups were comparable (P > 0.05).
      CONCLUSIONS: Ephedrine either 75 or 100 microg kg(-1) given before rapid tracheal
      intubation using propofol and rocuronium bromide improves the intubation
      conditions. It is not effective in preventing the hypotension which follows
      ensuing induction of anaesthesia.

PMID- 17510046
TI  - Cerebrovascular reactivity during hypothermia and rewarming.
AB  - BACKGROUND: Experimental evidence from a murine model of traumatic brain injury
      (TBI) suggests that hypothermia followed by fast rewarming may damage cerebral
      microcirculation. The effects of hypothermia and subsequent rewarming on cerebral
      vasoreactivity in human TBI are unknown. METHODS: This is a retrospective
      analysis of data acquired during a prospective, observational neuromonitoring and
      imaging data collection project. Brain temperature, intracranial pressure (ICP),
      and cerebrovascular pressure reactivity index (PRx) were continuously monitored.
      RESULTS: Twenty-four TBI patients with refractory intracranial hypertension were
      cooled from 36.0 (0.9) to 34.2 (0.5) degrees C [mean (sd), P < 0.0001] in 3.9
      (3.7) h. Induction of hypothermia [average duration 40 (45) h] significantly
      reduced ICP from 23.1 (3.6) to 18.3 (4.8) mm Hg (P < 0.05). Hypothermia did not
      impair cerebral vasoreactivity as average PRx changed non-significantly from 0.00
      (0.21) to -0.01 (0.21). Slow rewarming up to 37.0 degrees C [rate of rewarming,
      0.2 (0.2) degrees C h(-1)] did not increase ICP [18.6 (6.2) mm Hg] or PRx [0.06
      (0.18)]. However, in 17 (70.1%) out of 24 patients, rewarming exceeded the brain
      temperature threshold of 37 degrees C. In these patients, the average brain
      temperature was allowed to increase to 37.8 (0.3) degrees C (P < 0.0001), ICP
      remained stable at 18.3 (8.0) mm Hg (P = 0.74), but average PRx increased to 0.32
      (0.24) (P < 0.0001), indicating significant derangement in cerebrovascular
      reactivity. After rewarming, PRx correlated independently with brain temperature
      (R = 0.53; P < 0.05) and brain tissue O2 (R = 0.66; P < 0.01). CONCLUSIONS: After
      moderate hypothermia, rewarming exceeding the 37 degrees C threshold is
      associated with a significant increase in average PRx, indicating temperature
      dependent hyperaemic derangement of cerebrovascular reactivity.

PMID- 17510047
TI  - Quality of anaesthesia-related information accessed via Internet searches.
AB  - BACKGROUND: We conducted a study to examine the quality and stability of
      information available from the Internet on four anaesthesia-related topics.
      METHODS: In January 2006, we searched using four key words (porphyria,
      scleroderma, transfusion risk, and epidural analgesia risk) with five search
      engines (Google, HotBot, AltaVista, Excite, and Yahoo). We used a published
      scoring system (NetScoring) to evaluate the first 15 sites identified by each of
      these 20 searches. We also used a simple four-point scale to assess the first 100
      sites in the Google search on one of our four topics ('epidural analgesia risk').
      In November 2006, we conducted a second evaluation, using three search engines
      (Google, AltaVista, and Yahoo) with 14 synonyms for 'epidural analgesia risk'.
      RESULTS: The five search engines performed similarly. NetScoring scores were
      lower for transfusion risk (P < 0.001). One or more high-quality sites was
      identified consistently among the first 15 sites in each search. Quality scored
      using the simple scale correlated closely with medical content and design by
      NetScoring and with the number of references (P < 0.05). Synonyms of 'epidural
      analgesia risk' yielded similar results. The quality of accessed information
      improved somewhat over the 11 month period with Yahoo and AltaVista, but declined
      with Google. CONCLUSIONS: The Internet is a valuable tool for obtaining medical
      information, but the quality of websites varies between different topics. A
      simple rating scale may facilitate the quality scoring on individual websites.
      Differences in precise search terms used for a given topic did not appear to
      affect the quality of the information obtained.

PMID- 17510048
TI  - Enabling coupled quantitative genomics and proteomics analyses from rat spinal
      cord samples.
AB  - Translational research is progressing toward combined genomics and proteomics
      analyses of small and precious samples. In our analyses of spinal cord material,
      we systematically evaluated disruption and extraction techniques to determine an
      optimum process for the coupled analysis of RNA and protein from a single 5-mm
      segment of tissue. Analyses of these distinct molecular species were performed
      using microarrays and high resolution two-dimensional gels, respectively.
      Comparison of standard homogenization with automated frozen disruption (AFD)
      identified negligible differences in the relative abundance of genes (44) with
      all genes identified by either process. Analysis on either the Affymetrix or
      Applied Biosystems Inc. gene array platforms provided good correlations between
      the extraction techniques. In contrast, the AFD technique enabled identification
      of more unique proteins from spinal cord tissue than did standard homogenization.
      Furthermore use of an optimized CHAPS/urea extraction provided better protein
      recovery, as shown by quantitative two-dimensional gel analyses, than did solvent
      precipitation during TRIzol-based RNA extraction. Thus, AFD of tissue samples
      followed by protein and RNA isolation from separate aliquots of the frozen
      powdered sample is the most effective route to ensure full, quantitative analyses
      of both molecular entities.

PMID- 17510049
TI  - Reference-facilitated phosphoproteomics: fast and reliable phosphopeptide
      validation by microLC-ESI-Q-TOF MS/MS.
AB  - Recent advances in instrument control and enrichment procedures have enabled us
      to quantify large numbers of phosphoproteins and record site-specific
      phosphorylation events. An intriguing problem that has arisen with these advances
      is to accurately validate where phosphorylation events occur, if possible, in an
      automated manner. The problem is difficult because MS/MS spectra of
      phosphopeptides are generally more complicated than those of unmodified peptides.
      For large scale studies, the problem is even more evident because phosphorylation
      sites are based on single peptide identifications in contrast to protein
      identifications where at least two peptides from the same protein are required
      for identification. To address this problem we have developed an integrated
      strategy that increases the reliability and ease for phosphopeptide validation.
      We have developed an off-line titanium dioxide (TiO(2)) selective phosphopeptide
      enrichment procedure for crude cell lysates. Following enrichment, half of the
      phosphopeptide fractionated sample is enzymatically dephosphorylated, after which
      both samples are subjected to LC-MS/MS. From the resulting MS/MS analyses, the
      dephosphorylated peptide is used as a reference spectrum against the original
      phosphopeptide spectrum, in effect generating two peptide spectra for the same
      amino acid sequence, thereby enhancing the probability of a correct
      identification. The integrated procedure is summarized as follows: 1) enrichment
      for phosphopeptides by TiO(2) chromatography, 2) dephosphorylation of half the
      sample, 3) LC-MS/MS-based analysis of phosphopeptides and corresponding
      dephosphorylated peptides, 4) comparison of peptide elution profiles before and
      after dephosphorylation to confirm phosphorylation, and 5) comparison of MS/MS
      spectra before and after dephosphorylation to validate the phosphopeptide and its
      phosphorylation site. This phosphopeptide identification represents a major
      improvement as compared with identifications based only on single MS/MS spectra
      and probability-based database searches. We investigated an applicability of this
      method to crude cell lysates and demonstrate its application on the large scale
      analysis of phosphorylation sites in differentiating mouse myoblast cells.

PMID- 17510050
TI  - Absolute multiplexed quantitative analysis of protein expression during muscle
      development using QconCAT.
AB  - Stable isotope-labeled proteotypic peptides are used as surrogate standards for
      absolute quantification of proteins in proteomics. However, a stable isotope
      labeled peptide has to be synthesized, at relatively high cost, for each protein
      to be quantified. To multiplex protein quantification, we developed a method in
      which gene design de novo is used to create and express artificial proteins
      (QconCATs) comprising a concatenation of proteotypic peptides. This permits
      absolute quantification of multiple proteins in a single experiment. This
      complete study was constructed to define the nature, sources of error, and
      statistical behavior of a QconCAT analysis. The QconCAT protein was designed to
      contain one tryptic peptide from 20 proteins present in the soluble fraction of
      chicken skeletal muscle. Optimized DNA sequences encoding these peptides were
      concatenated and inserted into a vector for high level expression in Escherichia
      coli. The protein was expressed in a minimal medium containing amino acids
      selectively labeled with stable isotopes, creating an equimolar series of
      uniformly labeled proteotypic peptides. The labeled QconCAT protein, purified by
      affinity chromatography and quantified, was added to a homogenized muscle
      preparation in a known amount prior to proteolytic digestion with trypsin. As
      anticipated, the QconCAT was completely digested at a rate far higher than the
      analyte proteins, confirming the applicability of such artificial proteins for
      multiplexed quantification. The nature of the technical variance was assessed and
      compared with the biological variance in a complete study. Alternative ionization
      and mass spectrometric approaches were investigated, particularly LC-ESI-TOF MS
      and MALDI-TOF MS, for analysis of proteins and tryptic peptides. QconCATs offer a
      new and efficient approach to precise and simultaneous absolute quantification of
      multiple proteins, subproteomes, or even entire proteomes.

PMID- 17510051
TI  - Unsupervised fluorescence lifetime imaging microscopy for high content and high
      throughput screening.
AB  - Proteomics and cellomics clearly benefit from the molecular insights in cellular
      biochemical events that can be obtained by advanced quantitative microscopy
      techniques like fluorescence lifetime imaging microscopy and Forster resonance
      energy transfer imaging. The spectroscopic information detected at the molecular
      level can be combined with cellular morphological estimators, the analysis of
      cellular localization, and the identification of molecular or cellular
      subpopulations. This allows the creation of powerful assays to gain a detailed
      understanding of the molecular mechanisms underlying spatiotemporal cellular
      responses to chemical and physical stimuli. This work demonstrates that the high
      content offered by these techniques can be combined with the high throughput
      levels offered by automation of a fluorescence lifetime imaging microscope setup
      capable of unsupervised operation and image analysis. Systems and software
      dedicated to image cytometry for analysis and sorting represent important
      emerging tools for the field of proteomics, interactomics, and cellomics. These
      techniques could soon become readily available both to academia and the drug
      screening community by the application of new all-solid-state technologies that
      may results in cost-effective turnkey systems. Here the application of this
      screening technique to the investigation of intracellular ubiquitination levels
      of alpha-synuclein and its familial mutations that are causative for Parkinson
      disease is shown. The finding of statistically lower ubiquitination of the mutant
      alpha-synuclein forms supports a role for this modification in the mechanism of
      pathological protein aggregation.

PMID- 17510052
TI  - Primary structure, regioselectivity, and evolution of the membrane-bound fatty
      acid desaturases of Claviceps purpurea.
AB  - Two cDNAs with sequence similarity to fatty acid desaturase genes were isolated
      from the phytopathogenic fungus, Claviceps purpurea. The predicted amino acid
      sequences of the corresponding genes, named CpDes12 and CpDesX, share 87%
      identity. Phylogenetic analysis indicates that CpDes12 and CpDesX arose by gene
      duplication of an ancestral Delta(12)-desaturase gene after the divergence of
      Nectriaceae and Clavicipitaceae. Functional expression of CpDes12 and CpDesX in
      yeast (Saccharomyces cerevisiae) indicated that CpDes12 is primarily a
      "Delta(12)"-desaturase, whereas CpDesX is a novel desaturase catalyzing
      "Delta(12)," "Delta(15)," and "omega(3)" types of desaturation with omega(3)
      activity predominating. CpDesX sequentially desaturates both 16:1-9c and 18:1-9c
      to give 16:3-9c,12c,15c and 18:3-9c,12c,15c, respectively. In addition, it could
      also act as an omega(3)-desaturase converting omega(6)-polyunsaturates 18:3
      6c,9c,12c, 20:3-8c,11c,14c, and 20:4-5c,8c,11c,14c to their omega(3) counterparts
      18:4-6c,9c,12c,15c, 20:4-8c,11c,14c,17c, and 20:5-5c,8c,11c,14c,17c,
      respectively. By using reciprocal site-directed mutagenesis, we demonstrated that
      two residues (isoleucine at 152 and alanine at 206) are critical in defining the
      catalytic specificity of these enzymes and the C-terminal amino acid sequence
      (residues 302-477) was also found to be important. These data provide insights
      into the nature of regioselectivity in membrane-bound fatty acid desaturases and
      the relevant structural determinants. The authors suggest that the regios
      electivity of such enzymes may be best understood by considering the relative
      importance of more than one regioselective preference. In this view, CpDesX is
      designated as anu + 3(omega(3)) desaturase, which primarily references an
      existing double bond (nu + 3 regioselectivity) and secondarily shows preference
      for omega(3) desaturation.

PMID- 17510053
TI  - Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by
      scaffolding MK2 to Akt signal complex.
AB  - We have shown previously that Akt exists in a signal complex with p38 MAPK, MAPK
      activated protein kinase-2 (MK2), and heat shock protein 27 (Hsp27) and MK2
      phosphorylates Akt on Ser-473. Additionally, dissociation of Hsp27 from Akt,
      prior to Akt activation, induced polymorphonuclear leukocyte (PMN) apoptosis.
      However, the role of Hsp27 in regulating Akt activation was not examined. This
      study tested the hypothesis that Hsp27 regulates Akt activation and promotes cell
      survival by scaffolding MK2 to the Akt signal complex. Here we show that loss of
      Akt/Hsp27 interaction by anti-Hsp27 antibody treatment resulted in loss of
      Akt/MK2 interaction, loss of Akt-Ser-473 phosphorylation, and induced PMN
      apoptosis. Transfection of myristoylated Akt (AktCA) in HK-11 cells induced Akt
      Ser-473 phosphorylation, activation, and Hsp27-Ser-82 phosphorylation.
      Cotransfection of AktCA with Hsp27 short interfering RNA, but not scrambled short
      interfering RNA, silenced Hsp27 expression, without altering Akt expression in HK
      11 cells. Silencing Hsp27 expression inhibited Akt/MK2 interaction, inhibited Akt
      phosphorylation and Akt activation, and induced HK-11 cell death. Deletion
      mutagenesis studies identified acidic linker region (amino acids 117-128) on Akt
      as an Hsp27 binding region. Deletion of amino acids 117-128 on Akt resulted in
      loss of its interaction with Hsp27 and MK2 but not with Hsp90 as demonstrated by
      immunoprecipitation and glutathione S-transferase pulldown studies. Co
      transfection studies demonstrated that constitutively active MK2 (MK2EE)
      phosphorylated Aktwt (wild type) on Ser-473 but failed to phosphorylate
      Akt(Delta117-128) mutant in transfixed cells. These studies collectively define a
      novel role of Hsp27 in regulating Akt activation and cellular apoptosis by
      mediating interaction between Akt and its upstream activator MK2.

PMID- 17510054
TI  - Phosphorylation of both nucleoplasmin domains is required for activation of its
      chromatin decondensation activity.
AB  - Nucleoplasmin (NP) is a histone chaperone involved in nucleosome assembly,
      chromatin decondensation at fertilization, and apoptosis. To carry out these
      activities NP has to interact with different types of histones, an interaction
      that is regulated by phosphorylation. Here we have identified a number of
      phosphorylated residues by mass spectrometry and generated mutants in which these
      amino acids are replaced by Asp to mimic the effect of phosphorylation. Our
      results show that, among the eight phosphoryl groups experimentally detected,
      four are located at the flexible N terminus, and the rest are found at the tail
      domain, flanking the nuclear localization signal. Phosphorylation-mimicking
      mutations render a recombinant protein as active in chromatin decondensation as
      hyperphosphorylated NP isolated from Xenopus laevis eggs. Comparison of mutants
      in which the core and tail domains of the protein were independently or
      simultaneously "activated" indicates that activation or phosphorylation of both
      protein domains is required for NP to efficiently extract linker-type histones
      from chromatin.

PMID- 17510055
TI  - BARD1 translocation to mitochondria correlates with Bax oligomerization, loss of
      mitochondrial membrane potential, and apoptosis.
AB  - The breast cancer regulatory protein-1 (BRCA1)-associated RING domain 1 (BARD1)
      gene is mutated in a subset of breast/ovarian cancers. BARD1 functions as a
      heterodimer with BRCA1 in nuclear DNA repair. BARD1 also has a BRCA1-independent
      apoptotic activity. Here we investigated the link between cytoplasmic
      localization and apoptotic function of BARD1. We used immunofluorescence
      microscopy and deconvolution analysis to resolve BARD1 cytoplasmic staining
      patterns and detected endogenous BARD1 at mitochondria. BARD1 was also detected
      in mitochondrial cell fractions by immunoblotting. The targeting of BARD1 to
      mitochondria was modestly stimulated by DNA damage and did not require BRCA1 as
      indicated by RNA interference and peptide-competition experiments. Transiently
      expressed yellow fluorescence protein-BARD1 localized to mitochondria, and the
      targeting sequences were mapped to both the N and C terminus of BARD1. Ectopic
      yellow fluorescence protein-BARD1 induced apoptosis and loss of mitochondrial
      membrane potential in MCF-7 breast tumor cells. BARD1 apoptotic function was
      associated with stimulation of Bax oligomerization at mitochondria. This
      distinguishes it from BRCA1, which is pro-apoptotic but did not induce Bax
      oligomerization. The cancer-associated BARD1 splice-variant DeltaRIN (lacks the
      BRCA1 binding domain and ankyrin repeats) was recruited to mitochondria but did
      not stimulate apoptosis or alter membrane permeability. We propose that BARD1 has
      two main sites of action in its cellular response to DNA damage, the nucleus,
      where it promotes cell survival through DNA repair, and the mitochondria, where
      BARD1 regulates apoptosis.

PMID- 17510056
TI  - Nuclear factor-E2-related factor-1 mediates ascorbic acid induction of osterix
      expression via interaction with antioxidant-responsive element in bone cells.
AB  - We recently found that deletion of the gulonolactone oxidase gene, which is
      involved in the synthesis of ascorbic acid (AA), was responsible for the fracture
      phenotype in spontaneous fracture mice. To explore the molecular mechanisms by
      which AA regulates osteoblast differentiation, we examined the effect of AA on
      osterix expression via Nrf1 (NF-E2-related factor-1) binding to antioxidant
      responsive element (ARE) in bone marrow stromal (BMS) cells. AA treatment caused
      a 6-fold increase in osterix expression in mutant BMS cells at 24 h, which was
      unaffected by pretreatment with protein synthesis inhibitor. Sequence analyses of
      mouse osterix promoter revealed a putative ARE located at -1762 to -1733 upstream
      of the transcription start site to which Nrf potentially binds. A gel mobility
      shift assay revealed that nuclear proteins from AA-treated BMS cells bound to
      radiolabeled ARE much more strongly than nuclear extracts from AA-untreated
      cells. A chromatin immunoprecipitation assay with Nrf1 antibody confirmed the
      interaction of Nrf1 with the mouse osterix promoter. A reporter assay
      demonstrated that the promoter activity of mouse osterix containing an ARE was
      stimulated 4-fold by a 48-h treatment with AA in spontaneous fracture BMS cells.
      Treatment of mutant BMS cells with AA resulted in a 3.9-fold increase in the
      nuclear accumulation of Nrf1. Transfection of mutant BMS cells with Nrf1 small
      interfering RNA decreased Nrf1 protein by 4.5-fold, blocked AA induction of
      osterix expression, and impaired BMS cell differentiation. Our data provided the
      first experimental evidence that AA modulated osterix expression via a novel
      mechanism involving Nrf1 nuclear translocation and Nrf1 binding to ARE to
      activate genes critical for cell differentiation.

PMID- 17510057
TI  - PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of
      substrate binding.
AB  - Mammalian target of rapamycin (mTOR) functions in two distinct signaling
      complexes, mTORC1 and mTORC2. In response to insulin and nutrients, mTORC1,
      consisting of mTOR, raptor (regulatory-associated protein of mTOR), and mLST8, is
      activated and phosphorylates eukaryotic initiation factor 4E-binding protein
      (4EBP) and p70 S6 kinase to promote protein synthesis and cell size. Previously
      we found that activation of mTOR kinase in response to insulin was associated
      with increased 4EBP1 binding to raptor. Here we identify prolinerich Akt
      substrate 40 (PRAS40) as a binding partner for mTORC1. A putative TOR signaling
      motif, FVMDE, is identified in PRAS40 and shown to be required for interaction
      with raptor. Insulin stimulation markedly decreases the level of PRAS40 bound by
      mTORC1. Recombinant PRAS40 inhibits mTORC1 kinase activity in vivo and in vitro,
      and this inhibition depends on PRAS40 association with raptor. Furthermore,
      decreasing PRAS40 expression by short hairpin RNA enhances 4E-BP1 binding to
      raptor, and recombinant PRAS40 competes with 4E-BP1 binding to raptor. We,
      therefore, propose that PRAS40 regulates mTORC1 kinase activity by functioning as
      a direct inhibitor of substrate binding.

PMID- 17510058
TI  - FOXO1 regulates the expression of 4E-BP1 and inhibits mTOR signaling in mammalian
      skeletal muscle.
AB  - The mammalian target of rapamycin (mTOR) is regulated by growth factors to
      promote protein synthesis. In mammalian skeletal muscle, the Forkhead-O1
      transcription factor (FOXO1) promotes catabolism by activating ubiquitin-protein
      ligases. Using C2C12 mouse myoblasts that stably express inducible FOXO1-ER
      fusion proteins and transgenic mice that specifically overexpress constitutively
      active FOXO1 in skeletal muscle (FOXO(++/+)), we show that FOXO1 inhibits mTOR
      signaling and protein synthesis. Activation of constitutively active FOXO1
      induced the expression of eukaryotic initiation factor 4E-binding protein 1 (4E
      BP1) mRNA via binding to the promoter. This resulted in an increased total 4E-BP1
      abundance and a reduced 4E-BP1 (Thr-37/46) phosphorylation. The reduction in 4E
      BP1 phosphorylation was associated with a reduction in the abundance of Raptor
      and mTOR proteins, Raptor-associated mTOR, reduced phosphorylation of the
      downstream protein p70S6 kinase, and attenuated incorporation of
      [(14)C]phenylalanine into protein. The FOXO(++/+) mice, characterized by severe
      skeletal muscle atrophy, displayed similar patterns of mRNA expression and
      protein abundance to those observed in the constitutively active FOXO1 C2C12
      myotubes. These data suggest that FOXO1 may be an important therapeutic target
      for human diseases where anabolism is impaired.

PMID- 17510059
TI  - Germ line gain of function with SOS1 mutation in hereditary gingival
      fibromatosis.
AB  - Mutation of human SOS1 is responsible for hereditary gingival fibromatosis type
      1, a benign overgrowth condition of the gingiva. Here, we investigated molecular
      mechanisms responsible for the increased rate of cell proliferation in gingival
      fibroblasts caused by mutant SOS1 in vitro. Using ectopic expression of wild-type
      and mutant SOS1 constructs, we found that truncated SOS1 could localize to the
      plasma membrane, without growth factor stimuli, leading to sustained activation
      of Ras/MAPK signaling. Additionally, we observed an increase in the magnitude and
      duration of ERK signaling in hereditary gingival fibromatosis gingival
      fibroblasts that was associated with phosphorylation of retinoblastoma tumor
      suppressor protein and the up-regulation of cell cycle regulators, including
      cyclins C, D, and E and the E2F/DP transcription factors. These factors promote
      cell cycle progression from G(1) to S phase, and their up-regulation may underlie
      the increased gingival fibroblast proliferation observed. Selective depletion of
      wild-type and mutant SOS1 through small interfering RNA demonstrates the link
      between mutation of SOS1, ERK signaling, cell proliferation rate, and the
      expression levels of Egr-1 and proliferating cell nuclear antigen. These findings
      elucidate the mechanisms for gingival overgrowth mediated by SOS1 gene mutation
      in humans.

PMID- 17510060
TI  - SWI/SNF activity is required for the repression of deoxyribonucleotide
      triphosphate metabolic enzymes via the recruitment of mSin3B.
AB  - The SWI/SNF chromatin remodeling complex plays a critical role in the
      coordination of gene expression with physiological stimuli. The synthetic enzymes
      ribonucleotide reductase, dihydrofolate reductase, and thymidylate synthase are
      coordinately regulated to ensure appropriate deoxyribonucleotide triphosphate
      levels. Particularly, these enzymes are actively repressed as cells exit the cell
      cycle through the action of E2F transcription factors and the retinoblastoma
      tumor suppressor/p107/p130 family of pocket proteins. This process is found to be
      highly dependent on SWI/SNF activity as cells deficient in BRG-1 and Brm subunits
      fail to repress these genes with activation of pocket proteins, and this deficit
      in repression can be complemented, via the ectopic expression of BRG-1. The
      failure to repress transcription does not involve a blockade in the association
      of E2F or pocket proteins p107 and p130 with promoter elements. Rather, the
      deficit in repression is due to a failure to mediate histone deacetylation of
      ribonucleotide reductase, dihydrofolate reductase, and thymidylate synthase
      promoters in the absence of SWI/SNF activity. The basis for this is found to be a
      failure to recruit mSin3B and histone deacetylase proteins to promoters. Thus,
      the coordinate repression of deoxyribonucleotide triphosphate metabolic enzymes
      is dependent on the action of SWI/SNF in facilitating the assembly of repressor
      complexes at the promoter.

PMID- 17510061
TI  - Maspin binds to urokinase-type and tissue-type plasminogen activator through
      exosite-exosite interactions.
AB  - Maspin is a member of the serpin family with a reactive center loop that is
      incompatible with proteinase inhibition by the serpin conformational change
      mechanism. Despite this there are reports that maspin might regulate uPA
      dependent processes in vivo. Using exogenous and endogenous fluorescence, we
      demonstrate here that maspin can bind uPA and tPA in both single-chain and double
      chain forms, with K(d) values between 300 and 600 nM. Binding is at an exosite on
      maspin close to, but outside of, the reactive center loop and is therefore
      insensitive to mutation of Arg(340) within the reactive center loop. The binding
      site on tPA does not involve the proteinase active site, with the result that
      maspin can bind to S195A tPA that is already complexed to plasminogen activator
      inhibitor-1. The ability of maspin to bind these proteinases without involvement
      of the reactive center loop leaves the latter free to engage in additional, as
      yet unidentified, maspin-protein interactions that may serve to regulate the
      properties of the exosite-bound proteinase. This may help to reconcile apparently
      conflicting studies that demonstrate the importance of the reactive center loop
      in certain maspin functions, despite the inability of maspin to directly inhibit
      tPA or uPA catalytic activity in in vitro assays through engagement between its
      reactive center loop and the active site of the proteinase.

PMID- 17510062
TI  - Molecular recognition and interfacial catalysis by the essential
      phosphatidylinositol mannosyltransferase PimA from mycobacteria.
AB  - Mycobacterial phosphatidylinositol mannosides (PIMs) and metabolically derived
      cell wall lipoglycans play important roles in host-pathogen interactions, but
      their biosynthetic pathways are poorly understood. Here we focus on Mycobacterium
      smegmatis PimA, an essential enzyme responsible for the initial mannosylation of
      phosphatidylinositol. The structure of PimA in complex with GDP-mannose shows the
      two-domain organization and the catalytic machinery typical of GT-B
      glycosyltransferases. PimA is an amphitrophic enzyme that binds mono-disperse
      phosphatidylinositol, but its transferase activity is stimulated by high
      concentrations of non-substrate anionic surfactants, indicating that the early
      stages of PIM biosynthesis involve lipid-water interfacial catalysis. Based on
      structural, calorimetric, and mutagenesis studies, we propose a model wherein
      PimA attaches to the membrane through its N-terminal domain, and this association
      leads to enzyme activation. Our results reveal a novel mode of
      phosphatidylinositol recognition and provide a template for the development of
      potential antimycobacterial compounds.

PMID- 17510063
TI  - Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth
      factor-beta signaling.
AB  - Transforming growth factor-beta (TGF-beta) signaling is controlled by a variety
      of regulators that target either signaling receptors or activated Smad complexes.
      Among the negative regulators, Smad7 antagonizes TGF-beta signaling mainly
      through targeting the signaling receptors, whereas SnoN and c-Ski repress
      signaling at the transcriptional level through inactivation of Smad complexes. We
      previously found that Arkadia is a positive regulator of TGF-beta signaling that
      induces ubiquitin-dependent degradation of Smad7 through its C-terminal RING
      domain. We report here that Arkadia induces degradation of SnoN and c-Ski in
      addition to Smad7. Arkadia interacts with SnoN and c-Ski in their free forms as
      well as in the forms bound to Smad proteins, and constitutively down-regulates
      levels of their expression. Arkadia thus appears to effectively enhance TGF-beta
      signaling through simultaneous down-regulation of two distinct types of negative
      regulators, Smad7 and SnoN/c-Ski, and may play an important role in determining
      the intensity of TGF-beta family signaling in target cells.

PMID- 17510064
TI  - Dual subcellular localization in the endoplasmic reticulum and peroxisomes and a
      vital role in protecting against oxidative stress of fatty aldehyde dehydrogenase
      are achieved by alternative splicing.
AB  - Fatty aldehyde dehydrogenase (FALDH, ALDH3A2) is thought to be involved in the
      degradation of phytanic acid, a saturated branched chain fatty acid derived from
      chlorophyll. However, the identity, subcellular distribution, and physiological
      roles of FALDH are unclear because several variants produced by alternative
      splicing are present in varying amounts at different subcellular locations.
      Subcellular fractionation experiments do not provide a clear-cut conclusion
      because of the incomplete separation of organelles. We established human cell
      lines heterologously expressing mouse FALDH from each cDNA without tagging under
      the control of an inducible promoter and detected the variant FALDH proteins
      using a mouse FALDH-specific antibody. One variant, FALDH-V, was exclusively
      detected in peroxisomal membranes. Human FALDH-V with an amino-terminal Myc
      sequence also localized to peroxisomes. The most dominant form, FALDH-N, and
      other variants examined, however, were distributed in the endoplasmic reticulum.
      A gas chromatography-mass spectrometry-based analysis of metabolites in FALDH
      expressing cells incubated with phytol or phytanic acid showed that FALDH-V, not
      FALDH-N, is the key aldehyde dehydrogenase in the degradation pathway and that it
      protects peroxisomes from oxidative stress. In contrast, both FALDHs had a
      protective effect against oxidative stress induced by a model aldehyde for lipid
      peroxidation, dodecanal. These results suggest that FALDH variants are produced
      by alternative splicing and share an important role in protecting against
      oxidative stress in an organelle-specific manner.

PMID- 17510065
TI  - WRKY62 transcription factor acts downstream of cytosolic NPR1 and negatively
      regulates jasmonate-responsive gene expression.
AB  - Cytosolic NPR1 has been shown to be essential for the salicylic acid (SA)
      mediated suppression of jasmonic acid (JA)-responsive gene expression. However,
      factors downstream of NPR1 in the cross-talk between SA and JA signaling are
      unclear. Here we show that Arabidopsis WRKY62, a member of WRKY group III
      transcription factors, was induced by methyl jasmonate (MeJA) and SA treatment.
      The presence of basal SA is required for the MeJA-induced WRKY62 expression, and
      both chemicals exhibit a synergistic effect on WRKY62 induction. In addition,
      upon treatment with an extremely low concentration of SA, cytosolic NPR1 controls
      the MeJA-induced expression of WRKY62. TGA transcription factors, which up
      regulate SA-induced expression of WRKY62, are dispensable for the induction of
      WRKY62 in JA signaling. Genetic dissection of both wrky62 mutants and WRKY62
      overexpressing plants indicated that WRKY62 down-regulates JA-responsive LOX2 and
      VSP2 expression. Our results demonstrate that WRKY62 acts downstream of cytosolic
      NPR1 and negatively regulates JA-responsive gene expression, suggesting that
      WRKY62 may be involved in the SA-mediated suppression of JA signaling.

PMID- 17510066
TI  - Interindividual variability in the effect of atazanavir and saquinavir on the
      expression of lymphocyte P-glycoprotein.
AB  - OBJECTIVES: ABCB1 encodes the efflux transporter P-glycoprotein (P-gp), which
      regulates the intracellular concentration of many xenobiotics, including several
      HIV protease inhibitors (PIs). Exposure to some xenobiotics, such as the
      antibiotic rifampicin, increases P-gp expression. In the present study, we
      investigated the effect of the HIV PIs saquinavir and atazanavir on the
      expression and function of ABCB1 and P-gp in primary and cultured lymphocytes, as
      well as the molecular interactions between these drugs and P-gp. ABCB1 and P-gp
      expression and function were examined in lymphocyte samples from healthy subjects
      before and after atazanavir-boosted saquinavir treatment. Expression and function
      were also studied in CEM cells following exposure to atazanavir and saquinavir.
      The inhibitory effects of these drugs were investigated in ABCB1-transfected
      HEK293T cells. METHODS: P-gp expression and function were measured by flow
      cytometry. ABCB1 mRNA expression was evaluated using quantitative RT-PCR.
      RESULTS: There were no overall changes in ABCB1 or P-gp expression or function
      after saquinavir-atazanavir treatment in primary lymphocyte samples. However,
      there was considerable interindividual variability in baseline lymphocyte ABCB1
      expression, as well as in the degree of change in ABCB1 expression after
      saquinavir-atazanavir administration. In cell culture, 5 microM saquinavir
      increased ABCB1 levels, although it did not affect P-gp expression. Atazanavir
      inhibited P-gp function at concentrations above therapeutic levels. CONCLUSIONS:
      Differences in lymphocyte ABCB1 expression, which may be caused by genetic
      polymorphisms in ABCB1 or its regulatory partners, are a likely cause of
      interindividual variation in the disposition and efficacy of clinically relevant
      P-gp substrates, including HIV PIs.

PMID- 17510067
TI  - Aminopenicillin-induced exanthema allows treatment with certain cephalosporins or
      phenoxymethyl penicillin.
AB  - OBJECTIVES: Aminopenicillin-induced exanthema poses a problem in the management
      of infectious diseases. Due to theoretically possible immunological cross
      reactivity, all beta-lactam drugs, i.e. penicillins, penicillin derivatives and
      cephalosporins, are usually avoided. The available alternative antibiotics
      (macrolides, quinolones and glycopeptides) may be less effective, have more side
      effects, and their use increases medical costs. Moreover, their use contributes
      to the increasing bacterial resistance to antibiotics. The aim of the study is to
      demonstrate that patients with aminopenicillin-induced exanthema may receive
      specific beta-lactams for future antibiotic therapy. METHODS: Skin testing
      followed by oral challenges to identify beta-lactams that are tolerated by
      patients despite confirmed delayed-type non-immunoglobulin E (IgE)-mediated
      allergic hypersensitivity to aminopenicillins. RESULTS: Sixty-nine out of 71
      patients (97.2%) with non-IgE-mediated allergic hypersensitivity to
      aminopenicillins tolerate cephalosporins without an aminobenzyl side chain such
      as cefpodoxime or cefixime and 51 patients (71.8%) also tolerate phenoxymethyl
      penicillin. CONCLUSIONS: The majority of patients with non-IgE-mediated allergic
      hypersensitivity to aminopenicillins do not cross-react to certain cephalosporins
      or phenoxymethyl penicillin. Skin and drug challenge tests can be helpful to
      determine individual cross-reactivity.

PMID- 17510068
TI  - Commentary: Selected samples and nebulous measures: some methodological
      difficulties in life-course epidemiology.

PMID- 17510069
TI  - The predictive ability of self-assessed health for mortality in different
      educational groups.
AB  - BACKGROUND: The purpose of this study was to assess potential differences in the
      predictive ability of self-assessed health for mortality between educational
      groups, and to find explanations for any of these educational differences.
      METHODS: We used data from the longitudinal GLOBE study, with a 13-year mortality
      follow-up. Analyses were performed for people aged between 25-74 years at
      baseline (n = 16,722). The associations of self-assessed health with mortality
      were estimated with Cox regression analyses, and the resulting hazard ratios were
      used as indicators of the 'predictive ability' of self-assessed health for
      mortality. Differences between educational levels were estimated by including an
      interaction term of education with self-assessed health in regression models with
      mortality as the outcome. The analyses were subsequently adjusted for: life
      threatening chronic conditions, non-life threatening conditions, stressors and
      health behaviour, to test the contribution of these factors to the predictive
      ability of self-assessed health. RESULTS: Results indicated that the predictive
      ability of self-assessed health for mortality was greater in men with tertiary
      education as compared with the lowest educated men. No differences were observed
      in women. None of the four health aspects accounted for the educational
      difference in men. CONCLUSIONS: Because differences in the predictive ability for
      mortality were limited to the extreme educational groups in men, educational
      differences in self-assessed health that are reported in numerous studies should
      not be expected to seriously overestimate educational differences in 'objective'
      health status.

PMID- 17510070
TI  - Cohort Profile: the Chennai prospective study of mortality among 500,000 adults
      in Tamil Nadu, South India.

PMID- 17510071
TI  - Breast cancer mortality in Russia and Ukraine 1963-2002: an age-period-cohort
      analysis.
AB  - OBJECTIVE: To determine the reasons for the steady increase in breast cancer
      mortality in Russia and Ukraine. METHODS: Age-period-cohort analysis,
      supplemented by analysis of historical fertility trends. RESULTS: Mortality from
      breast cancer has risen steadily in both countries over the past 40 years,
      although faster in Russia than in Ukraine. There are strong birth cohort effects,
      which are consistent with known changes in fertility. Death rates were highest
      among those born in the first half of the 20th century, declining among those
      born after the 1950s. There has been a decline in mortality among younger women
      since the mid 1990s, which may reflect improvements in treatment. CONCLUSION: The
      increase in breast cancer mortality in Russia and Ukraine can largely be
      explained by known changes in fertility, while recent changes may reflect changes
      in treatment. Observed trends suggest that death rates from female breast cancer
      in the two countries are likely to stabilize or even decline in the future.

PMID- 17510072
TI  - Commentary: From phenotype, to genotype, to gene-environment interaction and risk
      for complex diseases.

PMID- 17510073
TI  - Commentary: Reflections on G. M. Lower and colleagues' 1979 study associating
      slow acetylator phenotype with urinary bladder cancer: meta-analysis, historical
      refinements of the hypothesis, and lessons learned.

PMID- 17510074
TI  - Cohort profile: the Cambridge City over-75s Cohort (CC75C).

PMID- 17510075
TI  - Acts of god.

PMID- 17510076
TI  - Socio-economic position at three points in life in association with type 2
      diabetes and impaired glucose tolerance in middle-aged Swedish men and women.
AB  - BACKGROUND: It has been suggested that low socio-economic position (SEP) during
      childhood and adolescence predicts risk of adult type 2 diabetes. We investigated
      the associations between type 2 diabetes and childhood SEP (fathers' occupational
      position), participants' education and adult SEP (participants' occupational
      position). To determine possible independent associations between early SEP
      (fathers' occupational position and participants' education) and disease, we
      adjusted for adult SEP and factors present in adult life associated with type 2
      diabetes. METHODS: This cross-sectional study comprised 3128 men and 4821 women
      aged 35-56 years. All subjects have gone through a health examination and
      answered a questionnaire on lifestyle factors. At the health centre, an oral
      glucose tolerance test was administered and identified 55 men and 52 women with
      previously undiagnosed type 2 diabetes. Relative risks (RRs) with 95% CIs were
      calculated in multiple logistic regression analyses. RESULTS: The age-adjusted
      RRs of type 2 diabetes if having a father with middle occupational position were
      2.3 [Confidence interval (CI:1.0-5.1) for women and, 2.0 (CI:0.7-5.6) for men].
      Moreover, low education was associated with type 2 diabetes in women, RR = 2.5
      (CI:1.2-4.9). Low occupational position in adulthood was associated with type 2
      diabetes in women, RR = 2.7 (CI:1.3-5.9) and men, RR = 2.9 (CI:1.5-5.7). The
      associations between early SEP and type 2 diabetes disappeared after adjustment
      for adult SEP and factors associated with type 2 diabetes. CONCLUSION: The
      association between type 2 diabetes and low SEP during childhood and adolescence
      in middle-aged Swedish subjects disappeared after adjustment for adult SEP and
      adult risk factors of diabetes.

PMID- 17510077
TI  - Accuracy of maternal reports of pre-schoolers' weights and heights as estimates
      of BMI values.
AB  - BACKGROUND: Data is lacking on the reliability of weight and height for young
      children as reported by parents participating in population-based studies. We
      analysed the accuracy of parental reports of children's weights and heights as
      estimates of body mass index, and evaluated the factors associated with the
      misclassification of overweight and obese children. METHODS: Analyses were
      conducted on a population-based birth cohort of 1549 4-year-old children from the
      province of Quebec (Canada) in 2002. Mothers reported weights and heights for the
      children as part of the regular annual data collection. Within the following 3
      months, children's weights and heights were measured at home as part of a
      nutrition survey. RESULTS: This study indicates that mothers overestimate their
      children's weight more than their height, resulting in an overestimation of
      overweight children of more than 3% in the studied population. Only 58% of the
      children were reported as overweight/obese with reported values. Maternal
      misreporting is more important for boys than girls, and for low socioeconomic
      status children compared with high socioeconomic status children. CONCLUSIONS:
      Research on the prevalence of overweight and obesity has often used self-reported
      measures of height and weight to estimate BMI. However, the results emphasize the
      importance of collecting measured data in childhood studies of overweight and
      obesity at the population level.

PMID- 17510078
TI  - Why might South Asians be so susceptible to central obesity and its atherogenic
      consequences? The adipose tissue overflow hypothesis.
AB  - The rates of coronary disease have accelerated dramatically amongst South Asians,
      driven to an important extent by the atherogenic dyslipidemia and type 2 diabetes
      that have become so common amongst them. These precursors of vascular disease
      appear at lower absolute amounts of adipose tissue in South Asians than in
      whites. In this paper, we set out a new hypothesis--the adipose tissue overflow
      hypothesis--to account for these findings. The adipose tissue mass within our
      bodies can be divided into three different compartments: superficial subcutaneous
      adipose tissue, deep subcutaneous adipose tissue and visceral adipose tissue. The
      superficial subcutaneous adipose tissue compartment is the primary compartment,
      is present throughout the body, and constitutes the vast majority of the adipose
      tissue in the lower limb. With energy excess, the secondary adipose tissue
      compartments--the deep subcutaneous (mainly upper body) and the visceral adipose
      tissue compartments--become more prominent. Superficial subcutaneous adipose
      tissue is relatively inert metabolically, whereas the other two compartments are
      characterized by higher transmembrane fatty acid flux rates and thus are more
      closely linked to dyslipidemia and dysglycemia. We hypothesize that the
      superficial subcutaneous adipose tissue compartment is larger in whites than in
      South Asians. If so, as obesity develops, South Asians exhaust the storage
      capacity of their superficial subcutaneous adipose tissue compartment before
      whites do and that is why they develop the metabolic complications of upper body
      obesity at lower absolute masses of adipose tissue than white people.

PMID- 17510079
TI  - Evidence for an intensity-dependent interaction of NAT2 acetylation genotype and
      cigarette smoking in the Spanish Bladder Cancer Study.
AB  - BACKGROUND: The N-acetyltransferase 2 (NAT2) enzyme detoxifies aromatic amines,
      an important class of carcinogens in tobacco smoke. Slow acetylation phenotype
      individuals have reduced detoxification capacity compared with those with a
      rapid/intermediate phenotype. Analysis of the Spanish Bladder Cancer Study found
      an odds ratio (OR) for slow acetylators relative to rapid/intermediate
      acetylators of 0.9 in never-smokers and 1.6 in ever-smokers, a 1.8-fold
      enhancement in smokers. Evidence indicates that acetylation is an exposure
      dependent process, and thus the magnitude of the interaction may also depend on
      exposure level. METHODS: We extend a comprehensive three-parameter linear
      exponential model for the excess odds ratio (EOR) for smoking to include effects
      of NAT2 status, and reanalyse smoking and NAT2 status for the bladder cancer
      data. RESULTS: We show that variations in smoking risk with NAT2 status result
      from interactions with smoking intensity (cigarettes per day) and not total pack
      years of exposure. In addition, the relative increase in smoking risk in NAT2 slo
      acetylators increases with smoking intensity. CONCLUSIONS: Analyses reveal an
      enhanced effect for smoking intensity and bladder cancer in NAT2 slow acetylators
      which increases with intensity.

PMID- 17510080
TI  - ARA54 is involved in transcriptional regulation of the cyclin D1 gene in human
      cancer cells.
AB  - Cyclin D1 is one of the major enhancers of cell cycle progression and its
      expression is regulated in several growth stimulatory signaling pathways. ARA54
      is an androgen receptor (AR) co-activator that enhances AR-dependent
      transcriptional activation. Although expression of ARA54 mRNA is observed in a
      variety of human tissues at low levels, the AR- or androgen-independent function
      of ARA54 in those tissues remains unclear. In this study, we identified a novel
      role for ARA54 in the regulation of cyclin D1 expression in the absence of AR
      stimulation in human cancer cells. Depletion of endogenous ARA54 by small
      interfering RNA decreased both the protein and mRNA levels of cyclin D1. These
      changes did not result from a reduction in the half-life of either the protein or
      the mRNA, but from suppression of cyclin D1 gene transcription. In T98G cells,
      depletion of ARA54 increased the population of cells in G(1) phase, but reduced
      the population of cells in S phase, leading to a significant increase in the
      G(1)/S ratio and impaired cell growth. Furthermore, the amount of ARA54 mRNA
      appeared to positively correlate with cyclin D1 mRNA levels in specimens of
      clinical colon carcinomas, indicating that ARA54 is not only involved in the
      regulation of cyclin D1 expression in cultured cell lines but also in clinical
      cancer specimens. These results suggest that ARA54 might participate in enhancing
      cell cycle progression and cell proliferation via induction of cyclin D1.

PMID- 17510081
TI  - Identification and chromosome mapping of loci predisposing to colorectal cancer
      that control Wnt/beta-catenin pathway and progression of early lesions in the
      rat.
AB  - Sporadic colorectal cancer (CRC) is a major health concern worldwide.
      Epidemiologic evidence suggests a polygenic predisposition to CRC, but the genes
      responsible remain unknown. Here, we performed genome-wide scanning of male
      (ACI/SegHsd x Wistar-Furth)F2 (AWF2) rats to map susceptibility genes influencing
      the evolution of early colorectal lesions to adenocarcinoma following 1,2
      dimethylhydrazine administration. Phenotypic analysis revealed higher
      incidence/multiplicity and lower size of adenomas in ACI/SegHsd (ACI) and
      (ACI/SegHsd x Wistar-Furth)F1 (AWF1) than Wistar-Furth (WF) rats and higher
      incidence/multiplicity of poorly differentiated adenocarcinomas in WF than ACI
      rats, with intermediate values in AWF1 rats. Linkage analysis of 138 AWF2 rats
      identified three loci on chromosomes 4, 15 and 18 in significant linkage with
      lesion multiplicity that were identified as rat Colon cancer resistance (rCcr) 1,
      rCcr2 and rCcr3, respectively. Seven other loci on chromosomes 5, 6, 15, 17, 18
      and 20 were in suggestive linkage with adenoma/adenocarcinoma
      multiplicity/surface area. Six of them were identified as rCcr4-9 and a locus on
      chromosome 5 was identified as a susceptibility locus, rCcs1. Significant
      interactions between rCcr3 and rCcr6, rCcr6 and rCcr8 and rCcr5 and rCcr9, and
      four novel epistatic loci controlling multiplicity/size of colorectal lesions
      were discovered. Apc, located at rCcr3, did not show functional promoter
      polymorphisms. However, influence of susceptibility/resistance genes on Wnt/beta
      catenin pathway was shown by defective beta-catenin inactivation in WF but not in
      ACI and AWF1 rat adenocarcinomas. These data indicate that inheritance of
      predisposition to CRC depends on interplays of several genetic factors, and
      suggest a possible mechanism of polygenic control of CRC progression.

PMID- 17510082
TI  - Aspirin blocks proliferation in colon cells by inducing a G1 arrest and apoptosis
      through activation of the checkpoint kinase ATM.
AB  - Colorectal cancer (CRC) is the most common gastrointestinal malignancy. Most of
      the clinical data on CRC prevention have come from the use of aspirin. Besides
      inhibition of cyclooxygenases, aspirin has a diversity of molecular effects that
      counteract colon carcinogenesis. Aspirin restrains cell proliferation by inducing
      a G1 arrest in colorectal cells. To determine which cell cycle checkpoint
      pathways are involved in this response, colorectal cell lines wild-type or
      defective for p53 and p21Waf1/Cip1 were treated with aspirin or the anti
      proliferative drug sulindac sulfide, then assayed for proliferative activity, for
      cell cycle progression and apoptosis, for the activation and phosphorylation of
      checkpoint components and for the transcriptional up-regulation of p21Waf1/Cip1
      and Bax. Aspirin and sulindac sulfide induced a G1 arrest within 48 h. While all
      cell lines responded in a comparable way to sulindac sulfide, the aspirin-induced
      G1 arrest was dependent on p21Waf1/Cip1--as cells lacking the cyclin-dependent
      kinase inhibitor failed to show this arrest--and on ataxia-telangiectasia-mutated
      kinase (ATM)--as the inhibitor caffeine abrogated the checkpoint. Moreover,
      aspirin induced cell death mainly in cells expressing p53. Aspirin induced the
      phosphorylation of p53 at residue Ser15 within 8 h in a caffeine-dependent
      manner, and also caused the activation of checkpoint kinase 2 and the cleavage of
      caspase 7. Our results suggest that aspirin induces a G1 arrest and apoptosis by
      activating p53 and p21Waf1/Cip1 in an ATM-dependent way. By activating these
      checkpoint pathways, aspirin may restrain uncontrolled proliferation of
      colorectal cells, enhance their response to stresses such as DNA damage and
      promote entry of abnormal cells into apoptosis.

PMID- 17510083
TI  - Significance of inflammation-associated regenerative mucosa characterized by
      Paneth cell metaplasia and beta-catenin accumulation for the onset of colorectal
      carcinogenesis in rats initiated with 1,2-dimethylhydrazine.
AB  - Short-term dextran sodium sulfate (DSS) treatment has been shown to notably
      accelerate colorectal tumor development in rats initiated with 1,2
      dimethylhydrazine (DMH). In the present study, to clarify mechanisms underlying
      the DSS influence, time-course studies of histopathological and
      immunohistochemical characteristics and beta-catenin gene mutations in colorectal
      mucosa in early stages of this model were conducted. F344 males were given three
      subcutaneous injections of DMH (40 mg/kg body wt) within a week, followed by free
      access to drinking water containing 1% DSS for a week. At weeks 1, 4, 6 and 8
      after the DSS treatment, rats were euthanized and colorectal samples were
      collected. At week 1, the colorectal mucosa demonstrated extensive erosion along
      with significant inflammatory cell infiltration and neighboring reactive
      hyperplasia. By week 4, the mucosal damage was repaired and regenerative mucosa,
      partly characterized by Paneth cell metaplasia and altered subcellular
      localization of beta-catenin, was apparent. Areas with Paneth cells/beta-catenin
      accumulation were significantly more likely to be accompanied by interstitial
      inflammation and 17 of 24 dysplastic foci were found in regenerative mucosa with
      Paneth cells. Furthermore, adenomas/carcinomas frequently featured various
      degrees of Paneth cell differentiation. Point mutations mainly in codons 34 and
      41 of beta-catenin gene were detected in 6 of 27 samples of regenerative mucosa
      with Paneth cells and four of nine dysplastic foci/adenomas/carcinomas. These
      findings indicate that inflammation-associated regenerative mucosa with Paneth
      cell metaplasia and alteration in the APC/beta-catenin/Tcf signal transduction
      pathway are possibly involved in the acceleration of colorectal carcinogenesis in
      this DMH-DSS rat model.

PMID- 17510084
TI  - Enhanced thyroid carcinogenicity of N-nitrosobis(2-oxopropyl)amine in Otsuka Long
      Evans Tokushima Fatty rats, a model of type II diabetes mellitus.
AB  - Epidemiologic data suggest that diabetes mellitus type II is a risk factor for
      several types of cancer, including pancreatic, liver, colon and thyroid cancers.
      In the present study, effects of diabetes/hyperlipidemia on N-nitrosobis(2
      oxopropyl)amine (BOP)-induced cancer development were examined in Otsuka Long
      Evans Tokushima Fatty (OLETF) rats, model animals for non-insulin-dependent
      diabetes mellitus and Long-Evans Tokushima Otsuka (LETO) rats, appropriate
      controls. Males of both strains were given four subcutaneous injections of BOP
      (10 mg/kg body wt) or saline on alternative days, starting at 5 weeks of age. BOP
      induced tumors in a variety of tissues, including the thyroid gland, colon,
      kidney, liver and lung. The highest yields were noted for thyroid tumors, the
      incidence (P = 0.0182) and multiplicity (P < 0.001) of BOP-induced thyroid
      cancers with marked fibrosis being significantly higher in OLETF than in LETO
      rats. Interestingly, anaplastic thyroid carcinomas were observed limited to the
      BOP-treated OLETF rats. Additionally, a greater incidence and frequency of
      aberrant crypt foci, putative precursor lesions for colon tumors, was observed in
      the BOP-treated OLETF group. However, BOP was ineffective at inducing pancreatic
      ductal tumors. No thyroid, liver, lung or colon tumors were found in the OLETF
      and LETO rats receiving the vehicle. Significant increases in serum levels of
      insulin, glucose, phospholipids, triglycerides and total cholesterol were
      detected in the OLETF rats compared with the LETO rats, regardless of the
      treatment. Our results indicate that diabetic/hyperlipidemic state can enhance
      BOP-induced carcinogenesis of the thyroid gland and to a lesser extent the colon
      in OLETF rats.

PMID- 17510085
TI  - Polychlorinated biphenyls modulated tumorigenesis in Sprague Dawley rats:
      correlation with mixed function oxidase activities and superoxide (O2* )
      formation potentials and implied mode of action.
AB  - Parallel, chronic (24 months) multidose bioassays of the PCB (polychlorinated
      biphenyls) Aroclors 1016, 1242, 1254, and 1260 in male and female Sprague-Dawley
      rats showed sex/Aroclor-dependent increases in hepatic tumors and decreases in
      extrahepatic tumors. To elucidate the PCB mode of action (MOA) involved, levels
      of a number of hypothesized mediators were measured in liver specimens collected
      at 3, 6, 12, 18, and 24 months and screened for correlation with late life
      hepatotumorigenesis (HT; mostly adenomas). Consistently correlated with HT were
      (1) tissue accumulations of SigmaPCBs (correlated in both sexes) and of dioxin
      equivalents (toxic equivalency [TEQ]; correlated in females only); (2) net
      activities of six groups of mixed function oxidases (MFOs), some PCB-induced,
      some PCB-repressed, as determined by differential metabolism of PCB congeners;
      (3) activities of deproteinated, reoxidized hepatic cytosols as catalysts for
      superoxide (O(2)(*-)) production, such activity having the chemical
      characteristics of redox-cycling quinones (RCQs), e.g., those derived from the
      glutathionylated estrogen catechols that were identified in the female rat
      livers; and (4) increased expression of the indicator of cell proliferation,
      proliferating cell nuclear antigen. The new findings, along with other recently
      reported relationships, were indicative of a MOA consisting of (1) SigmaPCB/TEQ
      accumulation in rat tissues; (2) SigmaPCB/TEQ repression of constitutive MFOs;
      (3) SigmaPCB/TEQ induction of other MFOs; (4) MFO-mediated formation of RCQs; (5)
      RCQ-mediated formation of O(2)(*-); (6) O(2)(*-) dismutation to H(2)O(2); and (7)
      H(2)O(2)-mediated mitotic signaling, resulting in the proliferation of
      spontaneously or otherwise initiated cells to form hepatic tumors, as in tumor
      promotion.

PMID- 17510087
TI  - Identifying people at risk for undiagnosed type 2 diabetes using the GP's
      electronic medical record.
AB  - BACKGROUND: Screening for type 2 diabetes is recommended in at-risk patients. The
      GP's electronic medical record (EMR) might be an attractive tool for identifying
      them. OBJECTIVE: To assess the value of the GP's EMR in identifying patients at
      risk for undiagnosed type 2 diabetes and the feasibility to use this information
      in usual care to initiate screening. METHODS: In 11 Dutch general practices (25
      GPs), we performed an EMR-derived risk assessment in all patients aged > or =45
      and < or =75 years, without known diabetes, identifying those at risk according
      to the American Diabetes Association recommendations. Patients with an EMR
      derived risk or risk after additional risk assessment during regular consultation
      were invited for capillary fasting plasma glucose (FPG) measurement. RESULTS: Of
      13 581 patients, 3858 (28%) had an EMR-based risk (hypertension, cardiovascular
      disease, lipid metabolism disorders and/or obesity). Additional risk assessment
      in those without an EMR-based risk showed that in 51%, greater than one risk
      factor was present, mainly family history (51.2%) and obesity (59%). Ninety per
      cent returned for the FPG measurement. In both groups, we found patients with an
      FPG exceeding the cut point for diabetes (5.9% versus 4.1%). CONCLUSIONS: With
      additional risk assessment during consultation, the GP's EMR was valuable in
      identifying patients at risk for undiagnosed type 2 diabetes. It was feasible to
      use this information to initiate screening. At-risk patients were willing to take
      part in screening. Better registration of family history and obesity will improve
      the EMR as a tool for identifying at-risk patients in opportunistic screening in
      general practice.

PMID- 17510088
TI  - Providing information about a flavor to preschoolers: effects on liking and
      memory for having tasted it.
AB  - This study sought to determine if providing affectively positive information
      about a flavor to preschool-aged children during tasting will increase
      recognition of and liking for the flavor and if the recognition and liking are
      associated. Forty-six 3- to 6-year-old children tasted 10 flavors: 5 presented
      with affectively positive information and 5 without. The 10 flavors were then
      presented again interspersed with 10 distracter flavors. Children reported
      whether they had tasted the flavor previously and provided hedonic ratings for
      each flavor. Children's ability to remember having tasted a flavor was greater
      when the flavor was presented with affectively positive information than without
      in children throughout the age range of 3-6 years. In children younger than 4.5
      years, the provision of information had no effect on hedonic rating, whereas in
      older children, the provision of information was associated with greater hedonic
      ratings. We conclude that providing affectively positive information to children
      about a flavor can increase their ability to recognize the flavor as previously
      tasted and increases hedonic rating of the flavor in children older than 4.5
      years.

PMID- 17510089
TI  - Increased behavioral and neuronal sensitivity to sex pheromone after brief odor
      experience in a moth.
AB  - Plasticity in the response to stimuli related to food and oviposition cues is
      well documented in insects. However, responses to cues related to reproduction,
      for example, sex pheromones, are considered to be innate and thus not affected by
      experience. Here we show that brief preexposure to sex pheromones, without
      ensuing reward, lowers the threshold for behavioral response and augments the
      sensitivity in antennal lobe interneurons to pheromone compared with naive male
      moths. Thus, the sex pheromone system in insects can be modulated by experience.
      In addition, we show that the behavioral attraction to sex pheromone increases
      after preexposure in a time-dependent manner: a short-term effect, possibly a
      form of sensitization, and a long-term effect after more than 24 h. The
      behavioral long-term effect is paralleled by an increase in sensitivity of
      interneurons in the primary olfactory center, whereas the peripheral olfactory
      system does not change its sensitivity. We hypothesize that short-term
      sensitization to sex pheromone serves as a kind of alert system, whereas the long
      term effect improves male performance when reproductively active females are
      present.

PMID- 17510090
TI  - Facial electromyography: responses of children to odor and taste stimuli.
AB  - The study investigated the potential for facial electromyography (EMG) to be used
      as a clinical tool for measuring the responses of children to pleasant and
      unpleasant smell and taste stimuli. Responses in the zygomaticus major and
      levator labii muscles to 4 odorants and 4 tastants were recorded from 34 children
      aged 6-9 years. The results indicated that EMG activities in the 2 muscles
      discriminated between pleasant and unpleasant stimuli within each modality in a
      manner that indicated that the children perceived the hedonic qualities of the
      stimuli in a manner similar to that reported for adults. Importantly, there was
      unanimous agreement across the children as regards the differential nature of the
      activities exhibited. These outcomes together with the results of earlier facial
      expression studies suggest that facial EMG may provide an objective procedure
      that could be suitable for the clinical assessment of taste and smell function in
      newborns and young infants.

PMID- 17510091
TI  - The obesity epidemic in the United States--gender, age, socioeconomic,
      racial/ethnic, and geographic characteristics: a systematic review and meta
      regression analysis.
AB  - This review of the obesity epidemic provides a comprehensive description of the
      current situation, time trends, and disparities across gender, age, socioeconomic
      status, racial/ethnic groups, and geographic regions in the United States based
      on national data. The authors searched studies published between 1990 and 2006.
      Adult overweight and obesity were defined by using body mass index (weight
      (kg)/height (m)(2)) cutpoints of 25 and 30, respectively; childhood "at risk for
      overweight" and overweight were defined as the 85th and 95th percentiles of body
      mass index. Average annual increase in and future projections for prevalence were
      estimated by using linear regression models. Among adults, obesity prevalence
      increased from 13% to 32% between the 1960s and 2004. Currently, 66% of adults
      are overweight or obese; 16% of children and adolescents are overweight and 34%
      are at risk of overweight. Minority and low-socioeconomic-status groups are
      disproportionately affected at all ages. Annual increases in prevalence ranged
      from 0.3 to 0.9 percentage points across groups. By 2015, 75% of adults will be
      overweight or obese, and 41% will be obese. In conclusion, obesity has increased
      at an alarming rate in the United States over the past three decades. The
      associations of obesity with gender, age, ethnicity, and socioeconomic status are
      complex and dynamic. Related population-based programs and policies are needed.

PMID- 17510092
TI  - Sustained low-efficiency dialysis as a treatment modality in a patient with
      lymphoma-associated lactic acidosis.

PMID- 17510093
TI  - A novel mutation in the GRHPR gene in a Japanese patient with primary
      hyperoxaluria type 2.

PMID- 17510094
TI  - Effect of cinacalcet cessation in renal transplant recipients with persistent
      hyperparathyroidism.
AB  - BACKGROUND: Persistent hyperparathyroidism after renal transplantation affects
      bone and allografts. Cinacalcet, a calcimimetic, reduces serum calcium and PTH in
      renal transplant recipients with persistent hyperparathyroidism. Here, we address
      the question whether this effect of cinacalcet persists after withdrawal.
      METHODS: Therefore, cinacalcet was stopped after 12 months treatment in 10 stable
      renal transplant patients. Serum calcium, phosphate, PTH, creatinine and cystatin
      C were monitored for 3 months. RESULTS: Serum calcium, normalized in nine
      patients before cessation of cinacalcet (2.32 +/- 0.05mmol/l, mean +/- SEM),
      increased after 3 months of discontinuation by 0.17 +/- 0.04mmol/l, P < 0.05, but
      remained within the normal range in eight patients. Compared with the time point
      of cessation, PTH remained unchanged or decreased further after 3 months without
      therapy in six patients. Measurements of cystatin C suggested an improvement of
      the glomerular filtration rate after cessation in 9 out of 10 patients (1.55 +/-
      0.09 vs 1.33 +/- 0.12 mg/l, P < 0.01). CONCLUSION: First, a beneficial effect of
      cinacalcet beyond the duration of a 12-month therapy appears to be present in
      some patients and second, the previously suspected influence of cinacalcet
      therapy on renal function is reversible. Thus, it is reasonable to consider a
      trial of cinacalcet cessation to identify these patients. The optimal time point
      for such a discontinuation is unknown. The present observations are preliminary.
      They clearly require a prospective randomized trial for definitive confirmation.

PMID- 17510095
TI  - Time-dependent changes in cardiac growth after kidney transplantation: the impact
      of pre-dialysis ventricular mass.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is common in chronic kidney
      disease (CKD), including kidney transplant recipients. However, time-related left
      ventricular mass changes (DeltaLVM) from pre-dialysis stage to beyond the first
      post-transplant year have not been clearly identified. METHODS: We studied a
      cohort of 60 stages 4-5 CKD patients without overt cardiac disease, who underwent
      three echocardiograms during follow-up: at pre-dialysis stage, on dialysis and
      after kidney transplantation (KT). Multiple linear regression was used to model
      DeltaLVM from baseline study. Cox proportional analysis was used to determine
      risk factors associated with either de novo LVH or>20% DeltaLVMI over time.
      RESULTS: Patients with baseline LVH (n=37; 61%) had a higher body mass index
      (BMI) than those without LVH (n=23; 39%) (P=0.013). BMI, haemoglobin levels
      (P=0.047) and non-use of angiotensin-converting enzyme inhibitors (ACEI)
      (P=0.057) were associated with baseline left ventricular mass index (LVMI).
      Twelve out of 23 patients (52%) with normal LVM at baseline, developed either de
      novo LVH or>20% DeltaLVMI at follow-up. On the other hand, 29 (78%) of those with
      initial LVH maintained this abnormality, and 8 (22%) normalized LVM post
      transplantation. Factors associated with DeltaLVMI were age (P=0.01), pre
      dialysis LVMI (P<0.0001), serum creatinine (P=0.012) and the use of ACEI post
      transplantation (P=0.009). In Cox analysis, pre-dialysis LVMI was associated with
      de novo LVH or>20% DeltaLVMI over time (hazard ratio 1.009; 95% confidence
      interval 1.004 to 1.015; P=0.001). CONCLUSIONS: Successful KT may not completely
      normalize LVM post-transplantation. Pre-dialysis LVMI, traditional risk factors
      and no use of ACEI may perpetuate cardiac growth following KT.

PMID- 17510096
TI  - The long-term outcome of 93 patients with proliferative lupus nephritis.
AB  - BACKGROUND: Few data are available about the very long-term outcome of patients
      with proliferative lupus nephritis. METHODS: Ninety-three Italian patients with
      biopsy-proven proliferative lupus nephritis (15 with class III, 9 with class
      III+V, 64 with class IV and 5 with class IV+V) followed for a median follow-up of
      15 years in a single renal unit were considered for this observational study.
      Patients were treated with an induction treatment consisting of high doses of
      corticosteroids plus immunosuppressive agents in the more severe cases. This
      treatment was repeated in the event of a renal flare. Then corticosteroids and
      immunosuppressive agents were reduced to the minimal effective dose for
      maintenance. RESULTS: Renal survival including death was 97% at 10 years and 82%
      at 20 years. At the last follow-up visit, 59 patients were in complete renal
      remission, 18 were in partial renal remission, four patients had chronic renal
      insufficiency, six had entered end-stage renal disease and six patients had died.
      At multivariate analysis the lack of achievement of complete renal remission and
      the occurrence of nephritic flares were significantly correlated both with the
      risk of doubling plasma creatinine and death or dialysis. Those patients who
      entered complete renal remission had significantly less probability of developing
      nephritic flares. CONCLUSION: The long-term prognosis of Caucasian patients with
      proliferative lupus nephritis may be better than usually thought. Favorable
      factors for good long-term outcome are the achievement of complete renal
      remission, the absence of nephritic flares and their complete reversibility after
      therapy.

PMID- 17510097
TI  - Expression of C-reactive protein in myointimal hyperplasia in a porcine
      arteriovenous graft model.
AB  - BACKGROUND: The migration and proliferation of myofibroblasts are prominent
      features of myointimal hyperplasia associated with haemodialysis
      polytetrafluoroethylene (PTFE) grafts. Since C-reactive protein (CRP) possesses
      functional activities on vascular smooth muscle cells (SMCs), we examined the
      expression of this protein in PTFE grafts early in the course of myointimal
      hyperplasia development in a porcine model. METHOD: Bilateral carotid-jugular
      PTFE loop grafts were placed in pigs. After euthanasia at 2-4 weeks, the graft
      venous and graft-arterial anastomoses and the adjacent blood vessels were excised
      en bloc and subjected to immunohistochemical analyses and in situ hybridization
      for CRP. The ability of CRP to stimulate proliferation was examined in cultured
      porcine venous SMCs using the bromodeoxyuridine assay after incubation for 48 h.
      RESULTS: Severe myointimal hyperplasia was found at 3 weeks after graft placement
      at both graft-venous and graft-arterial anastomoses. Compared to normal tissues,
      staining for CRP was far more intense in cells in the hyperplastic lesions at
      both anastomoses, which also stained positive for smooth muscle alpha-actin. In
      situ hybridization showed that these cells also expressed mRNA for CRP. At 1
      microg/ml, CRP increased the proliferation of cultured porcine venous SMCs by
      45.9+/-5.8%. CONCLUSION: CRP was produced in venous and arterial SMCs and its
      expression was enhanced in the hyperplastic lesions associated with arteriovenous
      PTFE grafts in a porcine model. Together with the ability of CRP to promote SMC
      proliferation, these data suggest that CRP might play a pathogenic role in the
      development of myointimal hyperplasia in PTFE grafts.

PMID- 17510098
TI  - Associations of a facility level decrease in dialysate sodium concentration with
      blood pressure and interdialytic weight gain.
AB  - BACKGROUND: Dialysate [Na+] is often overlooked as a contributor to hypertension
      in patients on haemodialysis (HD). We report observational experience with a
      facility level decrease in dialysate [Na+] from 141 mmol/l to 138 mmol/l, in the
      absence of concurrent change with respect to dietary sodium regulation. METHODS:
      The sample comprised all patients (n=52) dialysing at a single HD facility over
      an 8-month period flanking the change in dialysate [Na+]. Outcomes included
      repeated observations of blood pressure (BP), interdialytic weight gain (IDWG),
      pre-dialysis plasma [Na+] and adverse events. Predictors other than dialysate
      [Na+] included patient demographics, clinical characteristics and number of
      antihypertensive medications. The study used a longitudinal unbalanced panel
      design, and hierarchical linear and Poisson mixed models. RESULTS: In
      multivariate analyses, the change in dialysate [Na+] was associated with a
      statistically significant small to medium-sized decrease in pre- and post
      dialysis systolic and diastolic BP, pre-dialysis plasma [Na+], but not IDWG.
      Change was greatest in the patient tertile with the highest initial BP. There was
      no change in the frequency of adverse events. Modelling dialysate [Na+] exposure
      as the diffusion gradient from dialysate to blood water did not improve the
      strength of associations. CONCLUSIONS: A facility level decrease in dialysate
      [Na+] from 141 mmol/l to 138 mmol/l appears to be safe and well tolerated, and a
      useful means of improving BP control. The lack of change in IDWG probably
      reflects lack of dietary salt restriction, and but does raise the issue of volume
      independent effects of sodium exposure on BP.

PMID- 17510099
TI  - Complement hyperactivation may cause atypical haemolytic uraemic syndrome--gain
      of-function mutations in factor B.

PMID- 17510101
TI  - Probenecid-induced membranous nephropathy.

PMID- 17510100
TI  - Machine-generated bicarbonate dialysate for continuous therapy: a prospective,
      observational cohort study.
AB  - BACKGROUND: In 1995, we described the technique of adapting a haemodialysis (HD)
      machine to produce a composition-adjustable, bicarbonate-based fluid (as our
      primary source for dialysate) for continuous HD in intensive care unit (ICU)
      patients with acute renal failure (ARF). The following studies the clinical
      effects, biochemical changes and economic costs of this practice in a large
      cohort of patients at a single centre over the last 10 years. METHODS: The CCF
      ARF Support Registry (1995-2001) was used to identify 405 patients initially
      supported with bicarbonate continuous HD. The registry is a prospective,
      observational cohort database that captures demographic, dialysis therapy,
      laboratory and outcome data. All supported ARF patients were recorded from 1995
      98, and then one in five patients from 1999 to 2001. We also reviewed records of
      the individual dialysis procedures, dialysate disposal, dialysate monitoring
      tests and specific costs. RESULTS: Continuous HD was performed for 1292 +/- 587
      days from 1994 to 2004. Demographics [age 59.57 +/- 14.41 years, weight 84.2 +/-
      24 kg, male 65%, chronic kidney disease (CKD) 34%] and ICU mortality (60.5%) were
      comparable to other reported series. Day 4 solute [BUN 52.3 mg/dl (95% CI 49.6
      54.9), creatinine 2.79 mg/dl (95% CI 2.64-2.95)], electrolyte and acid-base
      balance [bicarbonate 24.12 mmol/l (95% CI 23.7-24.6)] were well controlled.
      Dialysate monitoring revealed no positive cultures or elevated endotoxin levels.
      Variable-composition dialysate was achieved and delivered to all patients without
      adverse consequences. The cost of dialysate actually declined over time (1995 =
      $0.91/l, 2005 = $0.67/l). CONCLUSION: We have demonstrated that ICU ARF patients
      can be safely, effectively and economically supported with continuous HD using
      this source.

PMID- 17510102
TI  - Detection and management of alcohol use disorders in German primary care
      influenced by non-clinical factors.
AB  - AIMS: The primary objective was to assess the proportion of detected and
      correctly referred patients in German primary care. The secondary objective was
      to identify patient and practitioner characteristics that predict detection and
      correct referral. METHODS: In this clustered cross-sectional survey in German
      primary care, 3003 patients were consecutively invited to participate, and were
      asked to fill in a standardized health questionnaire. They were then screened for
      problematic alcohol consumption using the Alcohol Use Disorders Identification
      Test. The physicians recorded their assessment of the presence of any alcohol use
      disorder and documented the treatment course of all identified patients for 3
      months. RESULTS: Correctly identified problem drinkers were 38.6% in a per
      protocol analysis and 33.6% using a worst-case scenario. Referral behaviour of
      physicians was in conformity with current practice guidelines in 64.6% of the
      documented cases and 27.0% in a worst-case scenario. Several patient (e.g. sex,
      age) and practitioner characteristics (e.g. age), which influence the diagnosis
      and referral of patients, could be identified. CONCLUSIONS: There is a clear need
      to increase the special diagnostic and therapeutic skills of general
      practitioners so that they may be able to indicate and perform secondary
      prevention. Further research should focus on the likely effects of the
      implementation of these diagnostic and management tools.

PMID- 17510103
TI  - A factor analysis of the important people inventory.
AB  - AIMS: For well over a decade, the Important People Inventory (IP, Clifford and
      Longabaugh, 1991; Clifford et al., 1992) has been used to collect a wide range of
      valuable information regarding network support for alcohol use. However, because
      of psychometric limitations and varied adaptations of the IP, the following study
      performed factor analyses to develop a more structurally consistent model of the
      scaleas compared to the existing model. METHODS: A first principal components
      analysis (Varimax rotation) was run on the indices of the IP using data from a
      national investigation of residents within a recovery community (N=897). Next, a
      second principal components analysis was run using data collected from
      participants recruited from inpatient treatment settings (N=150). RESULTS:
      Results indicated a nine-index, three-factor model, which explained about two
      thirds of the common variance. These three factors included: Support for Drinking
      from Network Members (3 items), Drinking Behaviours of Network Members (3 items),
      and General Social Support (3 items). CONCLUSIONS: Results of both studies
      suggest that the IP fits a multi-component structure. It is recommended that
      Drinking Behaviours of Network Members be examined for predictive validity and
      that General Social Support be removed from the scale or have additional items
      added.

PMID- 17510104
TI  - Implementing the NHS information technology programme: qualitative study of
      progress in acute trusts.
AB  - OBJECTIVES: To describe progress and perceived challenges in implementing the NHS
      information and technology (IT) programme in England. DESIGN: Case studies and in
      depth interviews, with themes identified using a framework developed from
      grounded theory. We interviewed personnel who had been interviewed 18 months
      earlier, or new personnel in the same posts. SETTING: Four NHS acute hospital
      trusts in England. PARTICIPANTS: Senior trust managers and clinicians, including
      chief executives, directors of IT, medical directors, and directors of nursing.
      RESULTS: Interviewees unreservedly supported the goals of the programme but had
      several serious concerns. As before, implementation is hampered by local
      financial deficits, delays in implementing patient administration systems that
      are compliant with the programme, and poor communication between Connecting for
      Health (the agency responsible for the programme) and local managers. New issues
      were raised. Local managers cannot prioritise implementing the programme because
      of competing financial priorities and uncertainties about the programme. They
      perceive a growing risk to patients' safety associated with delays and a loss of
      integration of components of the programme, and are discontented with Choose and
      Book (electronic booking for referrals from primary care). CONCLUSIONS: We
      recommend that the programme sets realistic timetables for individual trusts and
      advises managers about interim IT systems they have to purchase because of delays
      outside their control. Advice needs to be mindful of the need for trusts to
      ensure longer term compatibility with the programme and value for money. Trusts
      need assistance in prioritising modernisation of IT by, for example, including
      implementation of the programme in the performance management framework. Even
      with Connecting for Health adopting a different approach of setting central
      standards with local implementation, these issues will still need to be
      addressed. Lessons learnt in the NHS have wider relevance as healthcare systems,
      such as in France and Australia, look to realise the potential of large scale IT
      modernisation.

PMID- 17510105
TI  - Alarm symptoms in primary care.

PMID- 17510106
TI  - The value of administrative databases.

PMID- 17510107
TI  - Functional foods.

PMID- 17510108
TI  - Multimorbidity's many challenges.

PMID- 17510109
TI  - Thromboprophylaxis for adults in hospital.

PMID- 17510110
TI  - How to bring about changes.

PMID- 17510111
TI  - Role of primary care in improvement.

PMID- 17510112
TI  - More advice to clinicians.

PMID- 17510113
TI  - Time to stop doing tonsillectomies?

PMID- 17510114
TI  - The illusion of invulnerability.

PMID- 17510115
TI  - Cancerbackup sets record straight.

PMID- 17510116
TI  - Misuse of confidence intervals threatens conclusions.

PMID- 17510117
TI  - Combination shows no advantage over aspirin alone.

PMID- 17510118
TI  - Experts dispute claims of poor cancer survival in UK.

PMID- 17510120
TI  - Tackle cancer in Africa now to prevent catastrophe, say health activists.

PMID- 17510121
TI  - FDA calls for warnings on anaemia drugs amid reports of incentives to doctors.

PMID- 17510123
TI  - Israeli surgeons are reprimanded for allowing their names to appear on a study
      they had not done.

PMID- 17510124
TI  - New helpline will advise those who blow whistle on research fraud.

PMID- 17510129
TI  - Clinton brokers deal to lower price of antiretrovirals.

PMID- 17510130
TI  - Teenager carrying anencephalic fetus is granted right to travel to UK for
      abortion.

PMID- 17510132
TI  - Pfizer conducts survey of French patients on information provided by industry.

PMID- 17510133
TI  - Rise in prevalence of autism in children continues to baffle researchers.

PMID- 17510135
TI  - UK must learn from US's mistakes in tackling research misconduct.

PMID- 17510137
TI  - UK should foster scientific collaboration outside EU.

PMID- 17510138
TI  - It's "wrong" to put patients' records on IT system without explicit consent, MPs
      are told.

PMID- 17510148
TI  - NHS: the Blair years.

PMID- 17510149
TI  - The locked code.

PMID- 17510150
TI  - Cancer drugs: swallowing big pharma's line?

PMID- 17510151
TI  - Spend, spend, spend--hide, hide, hide.

PMID- 17510152
TI  - Functional foods: the case for closer evaluation.

PMID- 17510153
TI  - Genital herpes and its management.

PMID- 17510154
TI  - Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary
      embolism) in inpatients having surgery: summary of NICE guidance.

PMID- 17510155
TI  - Commentary: NICE--setting clinical standards.

PMID- 17510156
TI  - Minimally invasive treatment for liver and lung metastases in colorectal cancer.

PMID- 17510163
TI  - Alzforum and SWAN: the present and future of scientific web communities.
AB  - Scientists drove the early development of the World Wide Web, primarily as a
      means for rapid communication, document sharing and data access. They have been
      far slower to adopt the web as a medium for building research communities. Yet,
      web-based communities hold great potential for accelerating the pace of
      scientific research. In this article, we will describe the 10-year experience of
      the Alzheimer Research Forum ('Alzforum'), a unique example of a thriving
      scientific web community, and explain the features that contributed to its
      success. We will then outline the SWAN (Semantic Web Applications in
      Neuromedicine) project, in which Alzforum curators are collaborating with
      informatics researchers to develop novel approaches that will enable communities
      to share richly contextualized information about scientific data, claims and
      hypotheses.

PMID- 17510162
TI  - SenseLab: new developments in disseminating neuroscience information.
AB  - This article presents the latest developments in neuroscience information
      dissemination through the SenseLab suite of databases: NeuronDB, CellPropDB,
      ORDB, OdorDB, OdorMapDB, ModelDB and BrainPharm. These databases include
      information related to: (i) neuronal membrane properties and neuronal models, and
      (ii) genetics, genomics, proteomics and imaging studies of the olfactory system.
      We describe here: the new features for each database, the evolution of SenseLab's
      unifying database architecture and instances of SenseLab database interoperation
      with other neuroscience online resources.

PMID- 17510164
TI  - Responding to the health society.

PMID- 17510165
TI  - Secondary structure based analysis and classification of biological interfaces:
      identification of binding motifs in protein-protein interactions.
AB  - MOTIVATION: The increasing amount of data on protein-protein interaction needs to
      be rationalized for deriving guidelines for the alteration or design of an
      interface between two proteins. RESULTS: We present a detaild structural analysis
      and comparison of homo- versus heterodimeric protein-protein interfaces. Regular
      secondary structures (helices and strands) are the main components of the former,
      whereas non-regular structures (turns, loops, etc.) frequently mediate
      interactions in the latter. Interface helices get longer with increasing
      interface area, but only in heterocomplexes. On average, the homodimers have
      longer helical segments and prominent helix-helix pairs. There is a surprising
      distinction in the relative orientation of interface helices, with a tendency for
      aligned packing in homodimers and a clear preference for packing at 90 degrees in
      heterodimers. Arg and the aromatic residues have a higher preference to occur in
      all secondary structural elements (SSEs) in the interface. Based on the dominant
      SSE, the interfaces have been grouped into four classes: alpha, beta, alphabeta
      and non-regular. Identity between protein and interface classes is the maximum
      for alpha proteins, but rather mediocre for the other protein classes. The
      interface classes of the two chains forming a heterodimer are often dissimilar.
      Eleven binding motifs can capture the prominent architectural features of most of
      the interfaces.

PMID- 17510166
TI  - The Cytochrome P450 Engineering Database: a navigation and prediction tool for
      the cytochrome P450 protein family.
AB  - SUMMARY: The Cytochrome P450 Engineering Database (CYPED) has been designed to
      serve as a tool for a comprehensive and systematic comparison of protein
      sequences and structures within the vast and diverse family of cytochrome P450
      monooxygenases (CYPs). The CYPED currently integrates sequence and structure data
      of 3911 and 25 proteins, respectively. Proteins are grouped into homologous
      families and superfamilies according to Nelson's classification. Nonclassified
      CYP sequences are assigned by similarity. Functionally relevant residues are
      annotated. The web accessible version contains multisequence alignments,
      phylogenetic trees and HMM profiles. The CYPED is regularly updated and supplies
      all data for download. Thus, it provides a valuable data source for phylogenetic
      analysis, investigation of sequence-function relationships and the design of CYPs
      with improved biochemical properties. ABBREVIATIONS: Cytochrome P450 Engineering
      Database, CYPED; cytochrome P450 monooxygenase, CYP; Hidden Markov Model, HMM.
      AVAILABILITY: www.cyped.uni-stuttgart.de

PMID- 17510167
TI  - Probability-based pattern recognition and statistical framework for
      randomization: modeling tandem mass spectrum/peptide sequence false match
      frequencies.
AB  - MOTIVATION: In proteomics, reverse database searching is used to control the
      false match frequency for tandem mass spectrum/peptide sequence matches, but
      reversal creates sequences devoid of patterns that usually challenge database
      search software. RESULTS: We designed an unsupervised pattern recognition
      algorithm for detecting patterns with various lengths from large sequence
      datasets. The patterns found in a protein sequence database were used to create
      decoy databases using a Monte Carlo sampling algorithm. Searching these decoy
      databases led to the prediction of false positive rates for spectrum/peptide
      sequence matches. We show examples where this method, independent of
      instrumentation, database-search software and samples, provides better estimation
      of false positive identification rates than a prevailing reverse database
      searching method. The pattern detection algorithm can also be used to analyze
      sequences for other purposes in biology or cryptology. AVAILABILITY: On request
      from the authors. SUPPLEMENTARY INFORMATION: http://bioinformatics.psb.ugent.be/.

PMID- 17510168
TI  - Statistical prediction of protein chemical interactions based on chemical
      structure and mass spectrometry data.
AB  - MOTIVATION: Prediction of interactions between proteins and chemical compounds is
      of great benefit in drug discovery processes. In this field, 3D structure-based
      methods such as docking analysis have been developed. However, the genomewide
      application of these methods is not really feasible as 3D structural information
      is limited in availability. RESULTS: We describe a novel method for predicting
      protein-chemical interaction using SVM. We utilize very general protein data,
      i.e. amino acid sequences, and combine these with chemical structures and mass
      spectrometry (MS) data. MS data can be of great use in finding new chemical
      compounds in the future. We assessed the validity of our method in the dataset of
      the binding of existing drugs and found that more than 80% accuracy could be
      obtained. Furthermore, we conducted comprehensive target protein predictions for
      MDMA, and validated the biological significance of our method by successfully
      finding proteins relevant to its known functions. AVAILABILITY: Available on
      request from the authors.

PMID- 17510169
TI  - Isolated ZP-N domains constitute the N-terminal extensions of Zona Pellucida
      proteins.
AB  - Zona Pellucida (ZP) domains have been found in a wide variety of extracellular
      proteins, in which they play essential role for polymerization. They are shared
      by the ZP proteins, which constitute the extracellular coat of animal eggs.
      Except from ZP3, constituting the primary sperm receptor, the ZP proteins
      possess, in addition to their C-terminal ZP domains, N-terminal extensions, which
      are thought to play an important role in the species-specific gamete recognition.
      Here, we show that these extensions are made of single or multiple copies of a
      small globular domain, which can be significantly related to the N-terminal
      region of ZP domains (ZP-N domains). This finding brings new insights into the
      molecular evolution of ZP proteins, which may have evolved around a common ZP-N
      architecture, and more generally into the noticeable sequence diversity of ZP-N
      domains, which can be found as isolated subunits or tightly associated with ZP-C
      domains to form complete, canonical ZP domains.

PMID- 17510170
TI  - Computational identification of candidate loci for recessively inherited mutation
      using high-throughput SNP arrays.
AB  - MOTIVATION: Single nucleic polymorphisms (SNPs) are one of the most abundant
      genetic variations in the human genome. Recently, several platforms for high
      throughput SNP analysis have become available, capable of measuring thousands of
      SNPs across the genome. Tools for analysing and visualizing these large genetic
      data sets in biologically relevant manner are rare. This hinders effective use of
      the SNP-array data in research on complex diseases, such as cancer. RESULTS: We
      describe a computational framework to analyse and visualize SNP-array data, and
      link the results in relevant databases. Our major objective is to develop methods
      for identifying DNA regions that likely harbour recessive mutations. Thus, the
      algorithms are designed to have high sensitivity and the identified regions are
      ranked using a scoring algorithm. We have also developed annotation tools that
      automatically query gene IDs, exon counts, microarray probe IDs, etc. In our case
      study, we apply the methods for identifying candidate regions for recessively
      inherited colorectal cancer predisposition and suggest directions for wet-lab
      experiments. AVAILABILITY: R-package implementation is available at
      http://www.ltdk.helsinki.fi/sysbio/csb/downloads/CohortComparator/

PMID- 17510171
TI  - An evaluation of automated homology modelling methods at low target template
      sequence similarity.
AB  - MOTIVATION: There are two main areas of difficulty in homology modelling that are
      particularly important when sequence identity between target and template falls
      below 50%: sequence alignment and loop building. These problems become magnified
      with automatic modelling processes, as there is no human input to correct
      mistakes. As such we have benchmarked several stand-alone strategies that could
      be implemented in a workflow for automated high-throughput homology modelling.
      These include three new sequence-structure alignment programs: 3D-Coffee,
      Staccato and SAlign, plus five homology modelling programs and their respective
      loop building methods: Builder, Nest, Modeller, SegMod/ENCAD and Swiss-Model. The
      SABmark database provided 123 targets with at least five templates from the same
      SCOP family and sequence identities </=50%. RESULTS: When using Modeller as the
      common modelling program, 3D-Coffee outperforms Staccato and SAlign using both
      multiple templates and the best single template, and across the sequence identity
      range 20-50%. The mean model RMSD generated from 3D-Coffee using multiple
      templates is 15 and 28% (or using single templates, 3 and 13%) better than those
      generated by Staccato and Salign, respectively. 3D-Coffee gives equivalent
      modelling accuracy from multiple and single templates, but Staccato and SAlign
      are more successful with single templates, their quality deteriorating as
      additional lower sequence identity templates are added. Evaluating the different
      homology modelling programs, on average Modeller performs marginally better in
      overall modelling than the others tested. However, on average Nest produces the
      best loops with an 8% improvement by mean RMSD compared to the loops generated by
      Builder.

PMID- 17510172
TI  - Error detection in SNP data by considering the likelihood of recombinational
      history implied by three-site combinations.
AB  - MOTIVATION: Errors in nucleotide sequence and SNP genotyping data are problematic
      when inferring haplotypes. Previously published methods for error detection in
      haplotype data make use of pedigree information; however, for many samples,
      individuals are not related by pedigree. This article describes a method for
      detecting errors in haplotypes by considering the recombinational history implied
      by the patterns of variation, three SNPs at a time. RESULTS: Coalescent
      simulations provide evidence that the method is robust to high levels of
      recombination as well as homologous gene conversion, indicating that patterns
      produced by both proximate and distant SNPs may be useful for detecting unlikely
      three-site haplotypes. AVAILABILITY: The perl script implementing the described
      method is called EDUT (Error Detection Using Triplets) and is available on
      request from the authors. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 17510173
TI  - T-Pile--a package for thermodynamic calculations for biomolecules.
AB  - Molecular dynamics and Monte Carlo, usually conducted in canonical ensemble,
      deliver a plethora of biomolecular conformations. Proper analysis of the
      simulation data is a crucial part of biophysical and bioinformatics studies.
      Sequence alignment problem can be also formulated in terms of Boltzmann
      distribution. Therefore tools for efficient analysis of canonical ensemble data
      become extremely valuable. T-Pile package, presented here provides a user
      friendly implementation of most important algorithms such as multihistogram
      analysis and reweighting technique. The package can be used in studies of
      virtually any system governed by Boltzmann distribution. AVAILABILITY: T-Pile can
      be downloaded from: http://biocomp.chem.uw.edu.pl/services/tpile. These pages
      provide a comprehensive tutorial and documentation with illustrative examples of
      applications. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 17510174
TI  - Flat and bouncy walking.

PMID- 17510175
TI  - Imaging the activity of neuronal populations: when spikes don't flash and flashes
      don't spike.

PMID- 17510177
TI  - Dendritic Ca2+ signalling due to activation of alpha 7-containing nicotinic
      acetylcholine receptors in rat hippocampal neurons.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are in the superfamily of Cys
      loop ligand-gated ion channels, which are widely expressed in the brain. Among
      the many different subtypes of nAChRs known to be expressed in the rat brain, the
      alpha 7-containing nAChRs are considered to be the most permeable to Ca2+.
      Utilizing highly localized and rapid iontophoretic agonist delivery, combined
      with patch-clamp electrophysiology and fura-2 fluorescence imaging techniques, we
      examined the alpha 7 nAChR-mediated currents and [Ca2+]i transients in the
      dendrites of rat hippocampal CA1 interneurons in the slice. We found that in the
      dendrites, whereas the amplitudes of the current responses were smaller and the
      decay kinetics faster than the responses in the soma, the amplitudes of the
      [Ca2+]i signals were significantly larger. Cultured hippocampal neurons were
      studied since the dendritic field lies in the same focal plane, which allowed for
      a broader investigation of the spatiotemporal dynamics of [Ca2+]i signalling. In
      cultured neurons, the [Ca2+]i signals in the dendrites were similar to those in
      slices. Interestingly in cultures, even though the amplitude of the alpha 7 nAChR
      mediated currents dramatically decreased with distance from the soma (from
      approximately 20-250 microm), the amplitude of the [Ca2+]i signals did not
      correlate with distance. This indicates that the relative efficacy of alpha 7
      nAChR activation to increase [Ca2+]i levels in dendrites increased severalfold
      with distance from the soma. These results may have implications for the role
      that alpha 7 nAChRs have in regulating various signal transduction cascades,
      synaptic plasticity, and memory processes, via significant changes in [Ca(2+)]i
      levels.

PMID- 17510178
TI  - Two cAMP-dependent pathways differentially regulate exocytosis of large dense
      core and small vesicles in mouse beta-cells.
AB  - It has been reported that cAMP regulates Ca(2+)-dependent exocytosis via protein
      kinase A (PKA) and exchange proteins directly activated by cAMP (Epac) in neurons
      and secretory cells. It has, however, never been clarified how regulation of
      Ca(2+)-dependent exocytosis by cAMP differs depending on the involvement of PKA
      and Epac, and depending on two types of secretory vesicles, large dense-core
      vesicles (LVs) and small vesicles (SVs). In this study, we have directly
      visualized Ca(2+)-dependent exocytosis of both LVs and SVs with two-photon
      imaging in mouse pancreatic beta-cells. We found that marked exocytosis of SVs
      occurred with a time constant of 0.3 s, more than three times as fast as LV
      exocytosis, on stimulation by photolysis of a caged-Ca(2+) compound. The diameter
      of SVs was identified as approximately 80 nm with two-photon imaging, which was
      confirmed by electron-microscopic investigation with photoconversion of
      diaminobenzidine. Calcium-dependent exocytosis of SVs was potentiated by the cAMP
      elevating agent forskolin, and the potentiating effect was unaffected by
      antagonists of PKA and was mimicked by the Epac-selective agonist 8-(4
      chlorophenylthio)-2'-O-methyl cAMP, unlike that on LVs. Moreover, high-glucose
      stimulation induced massive exocytosis of SVs in addition to LVs, and photolysis
      of caged cAMP during glucose stimulation caused potentiation of exocytosis with
      little delay for SVs but with a latency of 5 s for LVs. Thus, Epac and PKA
      selectively regulate exocytosis of SVs and LVs, respectively, in beta-cells, and
      Epac can regulate exocytosis more rapidly than PKA.

PMID- 17510179
TI  - ATP is the predominant sympathetic neurotransmitter in rat mesenteric arteries at
      high pressure.
AB  - Most studies of neurovascular transmission in isolated small mesenteric arteries
      have used either isometric recording techniques or measured vasoconstriction in
      vessels with no distending pressure. Here we have used pressure myography to
      assess the contribution of noradrenaline and ATP to sympathetic neurotransmission
      in rat second-order mesenteric arteries. In arteries pressurized to 30 or 90
      mmHg, activation of sympathetic axons with trains of electrical stimuli (50
      pulses, 0.5-10 Hz) evoked frequency-dependent vasoconstrictions that increased in
      amplitude at higher pressure. In the presence of the P2-receptor antagonist
      suramin (0.1 mM), the amplitude of vasoconstrictions to trains at 2 and 10 Hz did
      not differ at 30 and 90 mmHg. In contrast, in the presence of the alpha(1)
      adrenoceptor antagonist prazosin (0.1 microm) vasoconstrictions at 90 mmHg were
      larger than those at 30 mmHg. At both pressures, the combination of prazosin and
      suramin virtually abolished constrictions. The purinergic component of
      vasoconstriction (prazosin-resistant) was almost abolished by the L-type Ca(2+)
      channel antagonist nifedipine (1 microm). Increasing pressure from 30 to 90 mmHg
      decreased the resting membrane potential and increased the amplitude of
      purinergic excitatory junction potentials. These findings indicate that the
      contribution of ATP to neurovascular transmission increases when the pressure is
      raised from 30 to 90 mmHg, which is similar to the pressure second-order
      mesenteric arteries experience in vivo, and that Ca(2+) influx through L-type
      Ca(2+) channels is largely responsible for purinergic activation of the vascular
      smooth muscle.

PMID- 17510180
TI  - Remodelling of the SUR-Kir6.2 interface of the KATP channel upon ATP binding
      revealed by the conformational blocker rhodamine 123.
AB  - ATP-sensitive K+ channels (K(ATP) channels) are metabolic sensors formed by
      association of a K+ channel, Kir6, and an ATP-binding cassette (ABC) protein,
      SUR, which allosterically regulates channel gating in response to nucleotides and
      pharmaceutical openers and blockers. How nucleotide binding to SUR translates
      into modulation of Kir6 gating remains largely unknown. To address this issue, we
      have used a novel conformational KATP channel inhibitor, rhodamine 123 (Rho123)
      which targets the Kir6 subunit in a SUR-dependent manner. Rho123 blocked SUR-less
      Kir6.2 channels with an affinity of approximately 1 microM, regardless of the
      presence of nucleotides, but it had no effect on channels formed by the
      association of Kir6.2 and the N-terminal transmembrane domain TMD0 of SUR. Rho123
      blocked SUR + Kir6.2 channels with the same affinity as Kir6.2 but this effect
      was antagonized by ATP. Protection from Rho123 block by ATP was due to direct
      binding of ATP to SUR and did not entail hydrolysis because it was not mimicked
      by AMP, did not require Mg2+ and was reduced by mutations in the nucleotide
      binding domains of SUR. These results suggest that Rho123 binds at the TMD0
      Kir6.2 interface and that binding of ATP to SUR triggers a change in the
      structure of the contact zone between Kir6.2 and domain TMD0 of SUR that causes
      masking of the Rho123 site on Kir6.2.

PMID- 17510181
TI  - Outward stabilization of the S4 segments in domains III and IV enhances lidocaine
      block of sodium channels.
AB  - The anti-arrhythmic drug lidocaine has been shown to have a lower affinity for
      block of voltage-gated sodium channels at hyperpolarized potentials compared to
      depolarized potentials. Concomitantly, lidocaine reduces maximum gating charge
      (Qmax) by 40% resulting from the complete stabilization of the S4 in domain III
      in an outward, depolarized position and partial stabilization of the S4 in domain
      IV in wild-type Na+ channels (Na(V)1.5). To investigate whether the pre
      positioning of the S4 segments in these two domains in a depolarized conformation
      increases affinity for lidocaine block, a cysteine residue was substituted for
      the 3rd outermost charged residue in the S4 of domain III (R3C-DIII) and for the
      2nd outermost Arg in S4 of domain IV (R2C-DIV) in Na(V)1.5. After biotinylation
      by exposure to extracellular MTSEA-biotin the mutated S4s became stabilized in an
      outward, depolarized position. For Na+ channels containing both mutations (R3C
      DIII + R2C-DIV) the IC50 for rested-state lidocaine block decreased from 194 +/-
      15 microM in control to 28 +/- 2 microM after MTSEA-biotin modification. To
      determine whether an intact inactivation gate (formed by the linker between
      domains III and IV) was required for local anaesthetic drugs to modify Na+
      channel gating currents, a Cys was substituted for the Phe in the IFM motif of
      the inactivation gate (ICM) and then modified by intracellular MTSET (WT
      ICM(MTSET)) before exposure to intracellular QX-222, a quarternary amine.
      Although WT-ICM(MTSET) required higher concentrations of drug to block I(Na)
      compared to WT, Qmax decreased by 35% and the V1/2 shifted leftward as previously
      demonstrated for WT. The effect of stabilization of the S4s in domains III and IV
      in the absence of an intact inactivation gate on lidocaine block was determined
      for R3C-DIII + ICM, R2C-DIV + ICM and R3C-DIII + R2C-DIV + ICM, and compared to
      WT-ICM. IC50 values were 1360 +/- 430 microM, 890 +/- 70 microM, 670 +/- 30
      microM and 1920 +/- 60 microM, respectively. Thermodynamic mutant-cycle analysis
      was consistent with additive (i.e. independent) contributions from stabilization
      of the individual S4s in R3C-DIII + ICM and R2C-DIV + ICM. We conclude that the
      positions of the S4s in domains III and IV are major determinants of the voltage
      dependence of lidocaine affinity.

PMID- 17510182
TI  - Synaptic influences on rat ganglion-cell photoreceptors.
AB  - The intrinsically photosensitive retinal ganglion cells (ipRGCs) provide a
      conduit through which rods and cones can access brain circuits mediating
      circadian entrainment, pupillary constriction and other non-image-forming visual
      functions. We characterized synaptic inputs to ipRGCs in rats using whole-cell
      and multielectrode array recording techniques. In constant darkness all ipRGCs
      received spontaneous excitatory and inhibitory synaptic inputs. Light stimulation
      evoked in all ipRGCs both synaptically driven ('extrinsic') and autonomous
      melanopsin-based ('intrinsic') responses. The extrinsic light responses were
      depolarizing, about 5 log units more sensitive than the intrinsic light response,
      and transient near threshold but sustained to brighter light. Pharmacological
      data showed that ON bipolar cells and amacrine cells make the most prominent
      direct contributions to these extrinsic light responses, whereas OFF bipolar
      cells make a very weak contribution. The spatial extent of the synaptically
      driven light responses was comparable to that of the intrinsic photoresponse,
      suggesting that synaptic contacts are made onto the entire dendritic field of the
      ipRGCs. These synaptic influences increase the sensitivity of ipRGCs to light,
      and also extend their temporal bandpass to higher frequencies. These extrinsic
      ipRGC light responses can explain some of the previously reported properties of
      circadian photoentrainment and other non-image-forming visual behaviours.

PMID- 17510183
TI  - Early alterations in the electrophysiological properties of rat spinal
      motoneurones following neonatal axotomy.
AB  - Early in development, motoneurones are critically dependent on their target
      muscles for survival and differentiation. Previous studies have shown that
      neonatal axotomy causes massive motoneurone death and abnormal function in the
      surviving motoneurones. We have investigated the electrophysiological and
      morphological properties of motoneurones innervating the flexor tibialis anterior
      (TA) muscle during the first week after a neonatal axotomy, at a time when the
      motoneurones would be either in the process of degeneration or attempting to
      reinnervate their target muscles. We found that a large number ( approximately
      75%) of TA motoneurones died within 3 weeks after neonatal axotomy. Intracellular
      recordings revealed a marked increase in motoneurone excitability, as indicated
      by changes in passive and active membrane electrical properties. These changes
      were associated with a shift in the motoneurone firing pattern from a
      predominantly phasic pattern to a tonic pattern. Morphologically, the dendritic
      tree of the physiologically characterized axotomized cells was significantly
      reduced compared with age-matched normal motoneurones. These data demonstrate
      that motoneurone electrical properties are profoundly altered shortly after
      neonatal axotomy. In a subpopulation of the axotomized cells, abnormally high
      motoneurone excitability (input resistance significantly higher compared with
      control cells) was associated with a severe truncation of the dendritic arbor,
      suggesting that this excitability may represent an early electrophysiological
      correlate of motoneurone degeneration.

PMID- 17510184
TI  - Task-related changes in propriospinal excitation from hand muscles to human
      flexor carpi radialis motoneurones.
AB  - This study addresses whether there is excitation from human hand muscles to
      flexor carpi radialis (FCR) motoneurones mediated through propriospinal circuits
      and, if so, whether it is used in specific motor tasks. Electrical stimuli to the
      ulnar nerve at wrist level produced an excitation in FCR motoneurones with
      characteristics typical of a propriospinally mediated effect: low threshold (0.6
      x motor threshold (MT)), a group I effect that was not reproduced by purely
      cutaneous stimuli, long central delay (4.1 +/- 0.4 ms in single units),
      suppression when the stimulus intensity was increased, and facilitation of the
      corticospinal excitation at the premotoneuronal level. Ulnar-induced
      propriospinally mediated excitation was compared during selective voluntary
      contractions of the FCR and, at equivalent level of FCR EMG, during tasks in
      which the FCR was activated automatically in postural contractions rather than
      voluntarily (grip, pinching and pointing). The excitation was significantly
      greater during grip (and pinching) than during voluntary FCR contractions and
      pointing, whether measured in single motor units or tonic EMG activity, or
      whether the response to motor cortex stimulation was assessed as the compound
      motor-evoked potential or the corticospinal peak in single units. The discrepancy
      between the tasks appeared with ulnar intensities above 0.8 x MT and was then
      present across a wide range of stimulus intensities. This suggests a reduction in
      the corticospinal control of 'feedback inhibitory interneurones' mediating
      peripheral inhibition to propriospinal neurones during grip and pinching. The
      resulting more effective background excitation of propriospinal neurones by the
      peripheral input from hand muscles could contribute to stabilizing the wrist
      during grip.

PMID- 17510185
TI  - Protein kinase A is activated by the n-3 polyunsaturated fatty acid
      eicosapentaenoic acid in rat ventricular muscle.
AB  - During cardiac ischaemia antiarrhythmic n-3 polyunsaturated fatty acids (PUFAs)
      are released following activation of phospholipase A2, if they are in the diet
      prior to ischaemia. Here we show a positive lusitropic effect of one such PUFA,
      eicosapentaenoic acid (EPA) in the antiarrhythmic concentration range in
      Langendorff hearts and isolated rat ventricular myocytes due to activation of
      protein kinase A (PKA). Several different approaches indicated activation of PKA
      by EPA (5-10 micromol l(-1)): the time constant of decay of the systolic Ca2+
      transient decreased to 65.3 +/- 5.0% of control, Western blot analysis showed a
      fourfold increase in phospholamban phosphorylation, and PKA activity increased by
      21.0 +/- 7.3%. In addition myofilament Ca2+ sensitivity was reduced in EPA; this
      too may have resulted from PKA activation. We also found that EPA inhibited L
      type Ca2+ current by 38.7 +/- 3.9% but this increased to 63.3 +/- 3.4% in 10
      micromol l(-1) H89 (to inhibit PKA), providing further evidence of activation of
      PKA by EPA. PKA inhibition also prevented the lusitropic effect of EPA on the
      systolic Ca2+ transient and contraction. Our measurements show, however, PKA
      activation in EPA cannot be explained by increased cAMP levels and alternative
      mechanisms for PKA activation are discussed. The combined lusitropic effect and
      inhibition of contraction by EPA may, respectively, combat diastolic dysfunction
      in ischaemic cardiac muscle and promote cell survival by preserving ATP. This is
      a further level of protection for the heart in addition to the well-documented
      antiarrhythmic qualities of these fatty acids.

PMID- 17510186
TI  - Contribution of alpha2-adrenoceptors and Y1 neuropeptide Y receptors to the
      blunting of sympathetic vasoconstriction induced by systemic hypoxia in the rat.
AB  - There is evidence that sympathetically evoked vasoconstriction in skeletal muscle
      is blunted in systemic hypoxia, but the mechanisms underlying this phenomenon are
      not clear. In Saffan-anaesthetized Wistar rats, we have studied the role of
      alpha(2)-adrenoceptors and neuropeptide Y (NPY) Y(1) receptors in mediating
      vasoconstriction evoked by direct stimulation of the lumbar sympathetic chain by
      different patterns of impulses in normoxia (N) and systemic hypoxia (H: breathing
      8% O(2)). Patterns comprised 120 impulses delivered in bursts over a 1 min period
      at 40 or 20 Hz, or continuously at 2 Hz. Hypoxia attenuated the evoked increases
      in femoral vascular resistance (FVR) by all patterns, the response to 2 Hz being
      most affected (40 Hz bursts: N = 3.25 +/- 0.75 arbitrary resistance units (RU); H
      = 1.14 +/- 0.29 RU). Yohimbine (Yoh, alpha(2)-adrenoceptor antagonist) or BIBP
      3226 (Y(1)-receptor antagonist) did not affect baseline FVR. In normoxia, Yoh
      attenuated the responses evoked by high frequency bursts and 2 Hz, whereas BIBP
      3226 only attenuated the response to 40 Hz (40 Hz bursts: N + Yoh = 2.1 +/- 0.59
      RU; N + BIBP 3226 = 1.9 +/- 0.4 RU). In hypoxia, Yoh did not further attenuate
      the evoked responses, but BIBP 3226 further attenuated the response to 40 Hz
      bursts. These results indicate that neither alpha(2)-adrenoceptors nor Y(1)
      receptors contribute to basal vascular tone in skeletal muscle, but both
      contribute to constrictor responses evoked by high frequency bursts of
      sympathetic activity. We propose that in systemic hypoxia, the alpha(2)-mediated
      component represents about 50% of the sympathetically evoked constriction that is
      blunted, whereas the contribution made by Y(1) receptors is resistant. Thus we
      suggest the importance of NPY in the regulation of FVR and blood pressure
      increases during challenges such as systemic hypoxia.

PMID- 17510187
TI  - A-type potassium channels differentially tune afferent pathways from rat solitary
      tract nucleus to caudal ventrolateral medulla or paraventricular hypothalamus.
AB  - The solitary tract nucleus (NTS) conveys visceral information to diverse central
      networks involved in homeostatic regulation. Although afferent information
      content arriving at various CNS sites varies substantially, little is known about
      the contribution of processing within the NTS to these differences. Using
      retrograde dyes to identify specific NTS projection neurons, we recently reported
      that solitary tract (ST) afferents directly contact NTS neurons projecting to
      caudal ventrolateral medulla (CVLM) but largely only indirectly contact neurons
      projecting to the hypothalamic paraventricular nucleus (PVN). Since intrinsic
      properties impact information transmission, here we evaluated potassium channel
      expression and somatodendritic morphology of projection neurons and their
      relation to afferent information output directed to PVN or CVLM pathways. In
      slices, tracer-identified projection neurons were classified as directly or
      indirectly (polysynaptically) coupled to ST afferents by EPSC latency
      characteristics (directly coupled, jitter < 200 micros). In each neuron, voltage
      dependent potassium currents (IK) were evaluated and, in representative neurons,
      biocytin-filled structures were quantified. Both CVLM- and PVN-projecting neurons
      had similar, tetraethylammonium-sensitive IK. However, only PVN-projecting NTS
      neurons displayed large transient, 4-aminopyridine-sensitive, A-type currents
      (IKA). PVN-projecting neurons had larger cell bodies with more elaborate
      dendritic morphology than CVLM-projecting neurons. ST shocks faithfully (> 75%)
      triggered action potentials in CVLM-projecting neurons but spike output was
      uniformly low (< 20%) in PVN-projecting neurons. Pre-conditioning
      hyperpolarization removed IKA inactivation and attenuated ST-evoked spike
      generation along PVN but not CVLM pathways. Thus, multiple differences in
      structure, organization, synaptic transmission and ion channel expression tune
      the overall fidelity of afferent signals that reach these destinations.

PMID- 17510188
TI  - In situ measurements of calpain activity in isolated muscle fibres from normal
      and dystrophin-lacking mdx mice.
AB  - Calpains are Ca(2+)-activated proteases that are thought to be involved in muscle
      degenerative diseases such as Duchenne muscular dystrophy. Status and activity of
      calpains in adult muscle fibres are poorly documented. We report here in situ
      measurements of calpain activity in collagenase-isolated fibres from C57 mice and
      form two models of dystrophy: dystrophin-deficient mdx and calpain-3 knocked-out
      mice. Calpain activity was measured using a permeant, fluorogenic substrate and
      its Ca(2+) dependence was studied. A 30-fold change of activity was observed
      between the lowest and the highest steady-state Ca(2+) availability. Fast
      transient changes of [Ca(2+)](i) induced by electrical stimulation or KCl
      dependent depolarization were ineffective in activating calpain. Slow [Ca(2+)]
      transients, as elicited during depletion of Ca(2+) stores, Ca(2+) store repletion
      and hypo-osmotic swelling were able to activate calpain. On return to resting
      conditions, calpain activity recovered its basal rate within 10 min. In resting
      intact muscle, mu-calpain was predominantly in the 80 kDa native form, with a
      small fraction in the 78 kDa autolysed form. The latter is thought to be
      responsible for the activity measured in our conditions. Calpain activity in mdx
      fibres showed an average 1.5-fold increase compared to activity in C57 fibres.
      This activity was reduced by a 10-fold lowering of [Ca(2+)](o). Calpain-3
      deficient fibres showed about the same increase, thus calpain-3 did not
      contribute to the activity measured here and calpain activation is not specific
      to dystrophin deficiency. In fibres from transgenic mice over-expressing
      calpastatin, a 40-50% reduction of calpain activity was observed, as with
      synthetic drugs (Z-Leu-Leu-CHO and SNT198438). We provide novel information on
      the physiological factors that control calpain activity in situ, particularly the
      effect of intracellular Ca(2+) transients that occur in excitation-contraction
      coupling, Ca(2+) store depletion and refilling, and activation of
      mechanosensitive Ca(2+) channels.

PMID- 17510189
TI  - KATP channel deficiency in mouse flexor digitorum brevis causes fibre damage and
      impairs Ca2+ release and force development during fatigue in vitro.
AB  - Activation of the K(ATP) channels results in faster fatigue rates as the channels
      depress action potential amplitude, whereas abolishing the channel activity has
      no effect in whole extensor digitorum longus (EDL) and soleus muscles. In this
      study, we examined the effects of abolished K(ATP) channel activity during
      fatigue at 37 degrees C on free intracellular Ca(2+) (Ca(2+)(i)) and tetanic
      force using single muscle fibres and small muscle bundles from the flexor
      digitorum brevis (FDB). K(ATP) channel deficient muscle fibres were obtained (i)
      pharmacologically by exposing wild-type fibres to glibenclamide, and (ii)
      genetically using null mice for the Kir6.2 gene (Kir6.2(-/-) mice). Fatigue was
      elicited using 200 ms tetanic contractions every second for 3 min. This study
      demonstrated for the first time that abolishing K(ATP) channel activity at 37
      degrees C resulted in faster fatigue rates, where decreases in peak Ca(2+)(i) and
      tetanic force were faster in K(ATP) channel deficient fibres than in control wild
      type fibres. Furthermore, several contractile dysfunctions were also observed in
      K(ATP) channel deficient muscle fibre. They included partially or completely
      supercontracted single muscle fibres, greater increases in unstimulated Ca(2+)(i)
      and unstimulated force, and lower force recovery. We propose that the observed
      faster rate of fatigue in K(ATP) channel deficient fibres is because the
      decreases in peak Ca(2+)(i) and force caused by contractile dysfunctions prevail
      over the expected slower decreases when the channels do not depress action
      potential amplitude.

PMID- 17510190
TI  - Maternal oxygen delivery is not related to altitude- and ancestry-associated
      differences in human fetal growth.
AB  - Fetal growth is reduced at high altitude, but the decrease is less among long
      resident populations. We hypothesized that greater maternal uteroplacental O(2)
      delivery would explain increased fetal growth in Andean natives versus European
      migrants to high altitude. O(2) delivery was measured with ultrasound, Doppler
      and haematological techniques. Participants (n=180) were pregnant women of self
      professed European or Andean ancestry living at 3600 m or 400 m in Bolivia.
      Ancestry was quantified using ancestry-informative single nucleotide
      polymorphism. The altitude-associated decrement in birth weight was 418 g in
      European versus 236 g in Andean women (P<0.005). Altitude was associated with
      decreased uterine artery diameter, volumetric blood flow and O(2) delivery
      regardless of ancestry. But the hypothesis was rejected as O(2) delivery was
      similar between ancestry groups at their respective altitudes of residence.
      Instead, Andean neonates were larger and heavier per unit of O(2) delivery,
      regardless of altitude (P<0.001). European admixture among Andeans was negatively
      correlated with birth weight at both altitudes (P<0.01), but admixture was not
      related to any of the O(2) transport variables. Genetically mediated differences
      in maternal O(2) delivery are thus unlikely to explain the Andean advantage in
      fetal growth. Of the other independent variables, only placental weight and
      gestational age explained significant variation in birth weight. Thus greater
      placental efficiency in O(2) and nutrient transport, and/or greater fetal
      efficiency in substrate utilization may contribute to ancestry- and altitude
      related differences in fetal growth. Uterine artery O(2) delivery in these
      pregnancies was 99 +/- 3 ml min(-1), approximately 5-fold greater than near-term
      fetal O(2) consumption. Deficits in maternal O(2) transport in third trimester
      normal pregnancy are unlikely to be causally associated with variation in fetal
      growth.

PMID- 17510191
TI  - TRPM7 channel is sensitive to osmotic gradients in human kidney cells.
AB  - TRPM7 (transient-receptor-potential melastatin 7) is an ion channel with alpha
      kinase function. TRPM7 is divalent-selective and regulated by a range of receptor
      stimulated second messenger pathways, intracellular Mg-nucleotides, divalent and
      polyvalent cations and pH. TRPM7 is ubiquitously found in mammalian cells,
      including kidney, the responsible organ for osmolyte regulation, posing the
      question whether the channel is osmosensitive. Recent reports investigated the
      sensitivity of native TRPM7-like currents to cell swelling with contradictory
      results. Here, we assess the sensitivity of TRPM7 to both hypo- and hyperosmotic
      conditions and explored the involvement of the channel's kinase domain. We find
      that hypotonicity facilitates TRPM7 at elevated intracellular magnesium and
      Mg.ATP (3-4 mm), but has no effect in the absence of these solutes. Hypertonic
      conditions, in contrast, inhibit TRPM7 with an IC(50) of 430 mosmol l(-1). This
      inhibitory effect is maintained in the complete absence of intra- and
      extracellular divalent ions, although shifted to higher osmolarities (IC(50) =
      510 mosmol l(-1)). TRPM7 senses osmotic gradients rather than ionic strength and
      this is independent of cAMP or not affected by cytochalasin D treatment.
      Furthermore, the kinase-domain deletion mutant of TRPM7 shows a similar behaviour
      to osmolarity as the wild-type protein, both in the presence and absence of
      divalent ions. This indicates that at least part of the osmosensitivity resides
      in the channel domain. Physiologically, TRPM7 channels do not seem to play an
      active role in regulatory volume changes, but rather those volume changes
      modulate TRPM7 activity through changes in the cytosolic concentrations of free
      Mg, Mg-nucleotides and a further unidentified factor. We conclude that TRPM7
      senses osmotically induced changes primarily through molecular crowding of
      solutes that affect channel activity.

PMID- 17510192
TI  - Computing vector differences using a gain field-like mechanism in monkey frontal
      eye field.
AB  - Signals related to eye position are essential for visual perception and eye
      movements, and are powerful modulators of sensory responses in many regions of
      the visual and oculomotor systems. We show that visual and pre-saccadic responses
      of frontal eye field (FEF) neurons are modulated by initial eye position in a way
      suggestive of a multiplicative mechanism (gain field). Furthermore the slope of
      the eye position sensitivity tends to be negatively correlated with preferred
      retinal position across the population. A model with Gaussian visual receptive
      fields and linear-rectified eye position gain fields accounts for a large portion
      of the variance in the recorded data. Using physiologically derived parameters,
      this model is able to subtract the gaze shift from the vector representing the
      retinal location of the target. This computation might be used to maintain a
      memory of target location in space during ongoing eye movements. This updated
      spatial memory can be read directly from the locus of the peak of activity across
      the retinotopic map of FEF and it is the result of a vector subtraction between
      retinal target location when flashed and subsequent eye displacement in the dark.

PMID- 17510193
TI  - Inactivation of inducible nitric oxide synthase protects intestinal pacemaker
      cells from postoperative damage.
AB  - Abdominal surgery causes postoperative gastrointestinal dysmotility which can
      progress to paralytic ileus. Surgery causes inflammatory responses leading to
      loss of interstitial cells of Cajal (ICC), which generate intestinal pacemaker
      activity. Here, we demonstrate that a deficiency in or pharmacological inhibition
      of inducible nitric oxide synthase (iNOS) before surgery protects ICC from
      postoperative damage. Ileal segments from wild-type, iNOS and cyclooxygenase-2
      (COX-2) knockout mice were resected and reconstructions were performed by end-to
      end anastomoses. Wild-type animals were exposed to iNOS inhibitors before
      surgery, and electrical activity and ICC were examined 5 h after surgery.
      Intestinal surgery on wild-type mice caused a significant reduction in ICC and
      pacemaking at distances up to 5 cm from the anastomosis site. ICC networks and
      pacemaking were protected in iNOS(-/-) mice. In animals treated preoperatively
      with iNOS inhibitors, pacemaker activity was depressed only at the anastomosis
      site. COX-2 deficiency also muted postoperative disruption in pacemaker activity.
      Postoperative surgical damage consists of a local response and a more widespread
      response in which ICC and pacemaker activity are disrupted. Damage to ICC and
      pacemaking was greatly attenuated in the absence of NO derived from iNOS. Thus,
      management of iNOS expression or activity prior to intestinal surgery protects
      against postsurgical dysmotility and reduces the severity of postoperative ileus.

PMID- 17510195
TI  - Differences in regulation of type I collagen synthesis in primary and passaged
      hepatic stellate cell cultures: the role of alpha5beta1-integrin.
AB  - Hepatic stellate cells (HSC) differ in their phenotype depending on the
      initiation and progression of their activation. Our hypothesis was that different
      mechanisms govern type I collagen synthesis depending on stage of HSC activation.
      We investigated the role of alpha(5)beta(1)-integrin as a regulator of type I
      collagen gene COL1A1 expression in primary and passaged HSC cultures using
      transgenic mouse containing type I collagen gene COL1A1 promoter linked to the
      chloramphenicol acetyltransferase (CAT) reporter gene. The alpha(5)beta(1)
      protein levels increased during the activation and were highest in day 6 primary
      cultures but decreased in passaged HSC. CAT activity, reflecting COL1A1
      expression, was upregulated by alpha(5)beta(1)-integrin. Inhibition of
      alpha(5)beta(1)-integrin by echistatin and blocking antibody resulted in reduced
      transgene activity only in early primary cultures (compared with the control,
      53.3 +/- 12% echistatin and 58.8 +/- 7% blocking antibody, respectively, P <
      0.05). Treatment of passaged HSC with either echistatin or blocking antibody had
      no effect. Fibronectin, an alpha(5)beta(1)-integrin ligand, increased transgene
      activity in primary (210 +/- 33%, P < 0.05) but not in passaged HSC cultures (119
      +/- 8%). This alpha(5)beta(1)-integrin effect appears to be at least in part
      mediated by CCAAT enhancer binding protein-beta (C/EBPbeta), because fibronectin
      increased and alpha(5)-gene silencing by small interfering RNA decreased
      C/EBPbeta levels. In addition, C/EBPbeta knockout mice showed reduced type I
      collagen synthesis compared with wild-type littermates. Therefore alpha(5)beta(1)
      integrin is an important regulator of type I collagen production in early primary
      HSC cultures but appears to have no direct role once the HSC are fully activated.

PMID- 17510194
TI  - Pioglitazone reverses insulin resistance and impaired CCK-stimulated pancreatic
      secretion in eNOS(-/-) mice: therapy for exocrine pancreatic disorders?
AB  - In mice, eNOS (endothelial nitric oxide synthase) maintains in vivo pancreatic
      secretory responses to carbachol or cholecystokinin octapeptide (CCK-8),
      maintains insulin sensitivity, and modulates pancreatic microvascular blood flow
      (PMBF). eNOS(-/-) mice are insulin resistant, and their exocrine pancreatic
      secretion is impaired. We hypothesized that the reduced exocrine pancreatic
      secretion in eNOS(-/-) mice is due to insulin resistance or impaired PMBF. To
      test this hypothesis, we gave eNOS(-/-) and wild-type (WT) mice pioglitazone (20
      or 50 mg.kg(-1).day(-1)), an insulin-sensitizing peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) activator, and measured pancreatic protein
      secretion evoked by CCK-8 (160 pmol.kg(-1).h(-1), a maximal stimulus). We also
      measured insulin resistance, serum glucose, C-peptide, insulin, pancreatic RNA
      digestive enzyme expression, and PMBF (microsphere technique). In WT mice,
      pioglitazone did not increase CCK-8-stimulated protein output over baseline. In
      eNOS(-/-) mice, however, pioglitazone substantially increased the low CCK-8
      stimulated protein output that is characteristic of these mutant mice (P <
      0.005). Pioglitazone abolished the CCK-8-evoked hyperinsulinemia (P < 0.005) and
      increased insulin sensitivity of eNOS(-/-) mice (P < 0.05), the latter based on
      hyperinsulinemic-euglycemic clamp studies. Pioglitazone had no effect on PMBF or
      pancreas mRNA expression of insulin or digestive enzymes. We conclude that in
      hyperinsulinemic eNOS(-/-) mice, a nonobese model of insulin resistance relevant
      to diabetes mellitus and possibly chronic pancreatitis, reduced pancreatic
      secretion is caused, at least in part, by insulin resistance. Insulin-sensitizing
      PPAR-gamma agonists such as pioglitazone may thus simultaneously correct
      endocrine and exocrine pancreatic disorders.

PMID- 17510196
TI  - Neonatal maternal separation of rat pups results in abnormal cholinergic
      regulation of epithelial permeability.
AB  - Neonatal maternal separation (MS) predisposes adult rats to develop stress
      induced mucosal barrier dysfunction/visceral hypersensitivity and rat pups to
      develop colonic epithelial dysfunction. Our aim was to examine if enhanced
      epithelial permeability in such pups resulted from abnormal regulation by enteric
      nerves. Pups were separated from the dam for 3 h/day (days 4-20); nonseparated
      (NS) pups served as controls. On day 20, colonic tissues were removed and mounted
      in Ussing chambers. Horseradish peroxidase (HRP) flux was used to measure
      macromolecular permeability. HRP flux was increased in MS versus NS pups. The
      enhanced flux was inhibited by the cholinergic muscarinic antagonist atropine and
      the nicotinic antagonist hexamethonium. The cholinergic component was greater in
      tissues from MS versus NS pups, suggesting that increased cholinergic activity
      was responsible for the MS elevated permeability. Western blots and
      immunohistochemistry of colonic tissues demonstrated increased expression of
      choline acetyltransferase (ChAT) in MS pups, indicating greater synthesis of
      acetylcholine. Since a previous study indicated that corticotrophin-releasing
      factor (CRF) mediates barrier dysfunction in MS pups, we examined if the two
      pathways were linked. In MS tissues, nonselective CRF receptor antagonism
      inhibited the enhanced flux, and the addition of atropine did not produce further
      inhibition. Using selective receptor antagonists, we identified that CRF receptor
      2 was involved in mediating this effect. These findings suggest that CRF, via CRF
      receptor 2, acts on cholinergic nerves to induce epithelial barrier dysfunction.
      Our study provides evidence that MS stimulates synthesis of acetylcholine, which,
      together with released CRF, creates a condition conducive to the development of
      epithelial barrier defects.

PMID- 17510197
TI  - PECAM-1 (CD 31) mediates transendothelial leukocyte migration in experimental
      colitis.
AB  - Transendothelial migration of circulating leukocytes into the colonic wall is a
      key step in the development of the inflammatory infiltrate in inflammatory bowel
      disease (IBD). The platelet-endothelial cell adhesion molecule-1 PECAM-1 (CD31)
      is expressed in the tight junction area of endothelial cells, where it is
      supposed to support the transmigration process. The aim of this study was to
      determine the role of PECAM-1 in experimental IBD and to show whether blockade of
      PECAM-1 has therapeutic effects. Chronic colitis was induced in female BALB/c
      mice by cyclic oral administration of dextran sodium sulfate (DSS) 3% (wt/vol).
      Expression of PECAM-1 was visualized by immunohistochemistry. In the treatment
      group animals received 1 mg/kg anti-PECAM-1 (2H8) ip daily starting on day 26. On
      day 30 leukocyte adhesion and migration was measured during N(2)O-isoflurane
      anesthesia in the distal colon by intravital microscopy. Disease activity index
      (DAI), histology, and MPO levels were compared with healthy and diseased
      controls. PECAM-1 was expressed in colitic mice. Chronic DSS colitis was
      characterized by a marked increase in rolling, adherent, and transmigrated
      leukocytes compared with healthy controls. Immunoblockade of PECAM-1 reduced
      leukocyte transmigration significantly and also diminished leukocyte rolling and
      sticking in an indirect manner. It also resulted in a significantly diminished
      DAI and MPO levels, as well as an amelioration of the histological inflammation
      score. PECAM-1 plays an important role in transendothelial leukocyte migration in
      DSS colitis. PECAM-1 could be a novel target for antibody-based treatment in IBD.

PMID- 17510198
TI  - Undernutrition enhances alcohol-induced hepatocyte proliferation in the liver of
      rats fed via total enteral nutrition.
AB  - To assess the relative contributions of undernutrition and ethanol (EtOH)
      exposure to alcohol-induced hepatotoxicity, female Sprague-Dawley rats were
      intragastrically infused liquid diets containing 187 or 154 kcal.kg(-3/4).day(-1)
      with or without 11 g.kg(-1).day(-1) EtOH. EtOH clearance was impaired in the 154
      kcal.kg(-3/4).day(-1) EtOH group (P < or = 0.05). A combination of undernutrition
      and EtOH also increased the induction of hepatic cytochrome P-450 (CYP)2E1 and
      CYP4A1 mRNA, apoprotein, and activities (P < or = 0.05). This was accompanied by
      increased oxidative stress (P < or = 0.05). The severity of liver steatosis,
      macrophage infiltration, and focal necrosis was comparable in both EtOH groups.
      Alanine aminotransferase levels were elevated (P < or = 0.05) but did not
      significantly differ between the two EtOH groups. TUNEL analysis also
      demonstrated a comparable increase in apoptosis in the two EtOH groups (P < or =
      0.05). The development of alcohol-induced liver pathology was accompanied by
      little change in fatty acid (FA) synthesis or degradation at 187 kcal.kg(
      3/4).day(-1) but at 154 kcal.kg(-3/4).day(-1) was accompanied by decreased
      expression of FA synthesis genes and increased expression of peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha)-regulated FA degradation
      pathways (P < or = 0.05). In addition, 154 kcal.kg(-3/4).day(-1) EtOH group
      livers exhibited greater hepatocyte proliferation (P < or = 0.05). We conclude
      that undernutrition does not exacerbate alcoholic steatohepatitis despite
      additional oxidative stress produced by an increased induction of CYP2E1 and
      CYP4A1. However, enhanced ethanol-induced cellular proliferation, perhaps as a
      result of enhanced PPAR-alpha signaling, may contribute to an increased risk of
      hepatocellular carcinoma in undernourished alcoholics.

PMID- 17510199
TI  - Membrane potential gradient is carbon monoxide-dependent in mouse and human small
      intestine.
AB  - The aims of this study were to quantify the change in resting membrane potential
      (RMP) across the thickness of the circular muscle layer in the mouse and human
      small intestine and to determine whether the gradient in RMP is dependent on the
      endogenous production of carbon monoxide (CO). Conventional sharp glass
      microelectrodes were used to record the RMPs of circular smooth muscle cells at
      different depths in the human small intestine and in wild-type, HO2-KO, and
      W/W(V) mutant mouse small intestine. In the wild-type mouse and human intestine,
      the RMP of circular smooth muscle cells near the myenteric plexus was -65.3 +/- 2
      mV and -58.4 +/- 2 mV, respectively, and -60.1 +/- 2 mV and -49.1 +/- 1 mV,
      respectively, in circular smooth muscle cells at the submucosal border.
      Oxyhemoglobin (20 microM), a trapping agent for CO, and chromium mesoporphyrin
      IX, an inhibitor of heme oxygenase, abolished the transwall gradient. The RMP
      gradients in mouse and human small intestine were not altered by N(G)-nitro-l
      arginine (200 microM). No transwall RMP gradient was found in HO2-KO mice and
      W/W(V) mutant mice. TTX (1 microM) and 1H-[1,2,4-]oxadiazolo[4,3-a]quinoxalin-1
      one (10 microM) had no effect on the RMP gradient. These data suggest that the
      gradient in RMP across the thickness of the circular muscle layer of mouse and
      human small intestine is CO dependent.

PMID- 17510200
TI  - The TSL neutron beam facility.
AB  - A new quasi-monoenergetic neutron beam facility has been constructed at The
      Svedberg Laboratory (TSL) in Uppsala, Sweden. Key features include a neutron
      energy range of 11-175 MeV, high fluxes, user flux control, flexible neutron
      field size and shape, and spacious and easily accessible user area. The first
      results of the beam characterisation measurements are reported.

PMID- 17510201
TI  - Experimental comparison of 241Am-Be neutron fluence energy distributions.
AB  - (241)Am-Be(alpha,n) neutron sources provide one of the most commonly used neutron
      fields for routine calibration of neutron sensitive devices. The neutron energy
      distribution of the IRSN standard (241)Am-Be source was measured in the energy
      region above 1.65 MeV using a BC501A proton-recoil liquid scintillator. The
      experimental data were compared to the ISO-recommended neutron energy
      distribution for an (241)Am-Be source. Some differences in shape were observed,
      with large variations mainly within the energy interval 3-6 MeV and around 8 MeV.
      Within the framework of a collaboration between three national metrological
      institutes (PTB, Germany; NPL, UK and LNE-IRSN, France), the neutron energy
      distributions of (241)Am-Be sources at each laboratory have been compared. The
      IRSN-BC501A proton-recoil scintillator was used to measure all the sources. The
      results show different energy distributions a priori influenced by the origin of
      the source, i.e. the manufacturing process. The maximum deviation observed for
      the integral dose equivalent, in the measured BC501A energy range, is within the
      4% uncertainty recommended by ISO standard 8529-2 to allow for variations of the
      neutron spectrum among different (241)Am-Be sources. However, knowledge of the
      energy distribution of an (241)Am-Be source provides a way to reduce the
      uncertainty in the dose equivalent rate delivered by such a source.

PMID- 17510202
TI  - Extension of applicable neutron energy of DARWIN up to 1 GeV.
AB  - The radiation-dose monitor, DARWIN, needs a set of response functions of the
      liquid organic scintillator to assess a neutron dose. SCINFUL-QMD is a Monte
      Carlo based computer code to evaluate the response functions. In order to improve
      the accuracy of the code, a new light-output function based on the experimental
      data was developed for the production and transport of protons deuterons,
      tritons, (3)He nuclei and alpha particles, and incorporated into the code. The
      applicable energy of DARWIN was extended to 1 GeV using the response functions
      calculated by the modified SCINFUL-QMD code.

PMID- 17510203
TI  - Numerical system utilising a Monte Carlo calculation method for accurate dose
      assessment in radiation accidents.
AB  - A system utilising radiation transport codes has been developed to derive
      accurate dose distributions in a human body for radiological accidents. A
      suitable model is quite essential for a numerical analysis. Therefore, two tools
      were developed to setup a 'problem-dependent' input file, defining a radiation
      source and an exposed person to simulate the radiation transport in an accident
      with the Monte Carlo calculation codes-MCNP and MCNPX. Necessary resources are
      defined by a dialogue method with a generally used personal computer for both the
      tools. The tools prepare human body and source models described in the input file
      format of the employed Monte Carlo codes. The tools were validated for dose
      assessment in comparison with a past criticality accident and a hypothesized
      exposure.

PMID- 17510204
TI  - Neutron-induced light-ion production from Fe, Pb and U at 96 MeV.
AB  - Double-differential cross-sections for light-ion production (up to A = 4) induced
      by 96 MeV neutrons have been measured for Fe, Pb and U. The experiments have been
      performed at The Svedberg Laboratory in Uppsala, using two independent devices,
      MEDLEY and SCANDAL. The recorded data cover a wide angular range (20 degrees -160
      degrees ) with low energy thresholds. The data have been normalised to obtain
      cross-sections using np elastic scattering events. The latter have been recorded
      with the same setup, and results for this measurement are reported. The work was
      performed within the HINDAS collaboration with the primary aim of improving the
      database for three of the most important nuclei for incineration of nuclear waste
      with accelerator-driven systems. The obtained cross-section data are of
      particular interest for the understanding of the so-called pre-equilibrium stage
      in a nuclear reaction and will be compared with model calculations.

PMID- 17510205
TI  - Radiation dose assessment at amang processing plants in Malaysia.
AB  - Measurements of external radiation level, radon/thoron daughters concentrations
      in air and uranium/thorium concentrations in airborne mineral dust at 16 amang
      plants in Malaysia were carried out for three consecutive months to assess
      radiation dose to workers. Estimated occupational dose was within the range of
      1.7-10.9 mSv y(-1). The mean total dose at the amang plants was 4.1 mSv y(-1).
      Overall, it was found that the major dose contribution of 80% came from external
      radiation. Radon/thoron daughters and airborne mineral dust contributed to only
      11 and 9% of the total dose, respectively.

PMID- 17510206
TI  - Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor,
      in combination with carboplatin and paclitaxel for advanced solid malignancies.
AB  - PURPOSE: The primary objective of this study was to determine the recommended
      phase II doses of the novel histone deacetylase inhibitor vorinostat when
      administered in combination with carboplatin and paclitaxel. EXPERIMENTAL DESIGN:
      Patients (N = 28) with advanced solid malignancies were treated with vorinostat,
      administered orally once daily for 2 weeks or twice daily for 1 week, every 3
      weeks. Carboplatin and paclitaxel were administered i.v. once every 3 weeks.
      Doses of vorinostat and paclitaxel were escalated in sequential cohorts of three
      patients. The pharmacokinetics of vorinostat, its metabolites, and paclitaxel
      were characterized. RESULTS: Vorinostat was administered safely up to 400 mg qd
      or 300 mg bd with carboplatin and paclitaxel. Two of 12 patients at the 400 mg qd
      schedule experienced dose-limiting toxicities of grade 3 emesis and grade 4
      neutropenia with fever. Non-dose-limiting toxicity included nausea, diarrhea,
      fatigue, neuropathy, thrombocytopenia, and anemia. Of 25 patients evaluable for
      response, partial responses occurred in 11 (10 non-small cell lung cancer and 1
      head and neck cancer) and stable disease occurred in 7. Vorinostat
      pharmacokinetics were linear over the dose range studied. Vorinostat area under
      the concentration versus time curve and half-life increased when vorinostat was
      coadministered with carboplatin and paclitaxel, but vorinostat did not alter
      paclitaxel pharmacokinetics. CONCLUSIONS: Both schedules of vorinostat (400 mg
      oral qd x 14 days or 300 mg bd x 7 days) were tolerated well in combination with
      carboplatin (area under the concentration versus time curve = 6 mg/mL x min) and
      paclitaxel (200 mg/m(2)). Encouraging anticancer activity was noted in patients
      with previously untreated non-small cell lung cancer.

PMID- 17510207
TI  - Phase I trial of weekly paclitaxel and BMS-214662 in patients with advanced solid
      tumors.
AB  - PURPOSE: To assess the maximum tolerated dose (MTD), dose-limiting toxicity
      (DLT), pharmacodynamics, and antitumor activity of continuous weekly-administered
      paclitaxel and BMS-214662, a novel farnesyl transferase inhibitor. EXPERIMENTAL
      DESIGN: Patients were treated every week as tolerated with i.v. paclitaxel (fixed
      dose, 80 mg/m(2)/wk) administered over 1 h followed by i.v. BMS-214662
      (escalating doses, 80-245 mg/m(2)/wk) over 1 h starting 30 min after completion
      of paclitaxel. RESULTS: Twenty-six patients received 94 courses (one course, 21
      days) of study treatment. Two patients received five courses of BMS-214662 as a
      weekly 24-h infusion (209 mg/m(2)/wk). The most common toxicities were grade 1 to
      2 nausea/vomiting and/or diarrhea. DLTs observed at or near the MTD (200
      mg/m(2)/wk) were grade 4 febrile neutropenia with sepsis occurring on day 2 of
      course 1 (245 mg/m(2)/wk), reversible grade 3 to 4 serum transaminase increases
      on day 2, and grade 3 diarrhea (200 and 245 mg/m(2)/wk). Objective partial
      responses were observed in patients with pretreated head and neck, ovarian, and
      hormone-refractory prostate carcinomas, and leiomyosarcoma. The observed
      pharmacokinetics of paclitaxel and BMS-214662 imply no interaction between the
      two. Significant inhibition (>80%) of farnesyl transferase activity in peripheral
      mononuclear cells was observed at the end of BMS-214662 infusion. CONCLUSIONS:
      Pretreated patients with advanced malignancies can tolerate weekly paclitaxel and
      BMS-214662 at doses that achieve objective clinical benefit. Due to multiple DLTs
      occurring at the expanded MTD, the recommended phase 2 dose and schedule is
      paclitaxel (80 mg/m(2) over 1 h) and BMS-214662 (160 mg/m(2) over 1 h)
      administered weekly.

PMID- 17510208
TI  - UGT1A1 polymorphism can predict hematologic toxicity in patients treated with
      irinotecan.
AB  - PURPOSE: Irinotecan (CPT-11) is approved in metastatic colorectal cancer
      treatment and can cause severe toxicity. The main purpose of our study was to
      assess the role of different polymorphisms on the occurrence of hematologic
      toxicities and disease-free survival in high-risk stage III colon cancer patients
      receiving 5-fluorouracil (5FU) and CPT-11 adjuvant chemotherapy regimen in a
      prospective randomized trial. EXPERIMENTAL DESIGN: Four hundred patients were
      randomized in a phase III trial comparing LV5FU2 to LV5FU2 + CPT-11. DNA from 184
      patients was extracted and genotyped to detect nucleotide polymorphism: 3435C>T
      for ABCB1, 6986A>G for CYP3A5, UGT1A1*28 and -3156G>A for UGT1A1. RESULTS:
      Genotype frequencies were similar in both treatment arms. In the test arm, no
      significant difference was observed in toxicity or disease-free survival for
      ABCB1 and CYP3A5 polymorphisms. UGT1A1*28 homozygous patients showed more
      frequent severe hematologic toxicity (50%) than UGT1A1*1 homozygous patients
      (16.2%), P = 0.06. Moreover, patients homozygous for the mutant allele of 
      3156G>A UGT1A1 polymorphism showed more frequent severe hematologic toxicity
      (50%) than patients homozygous for wild-type allele (12.5%), P = 0.01. This
      toxicity occurred significantly earlier in homozygous mutant than wild-type
      homozygous patients (P = 0.043). In a Cox model, the hazard ratio for severe
      hematologic toxicity is significantly higher for patients with the A/A compared
      with the G/G genotype [hazard ratio, 8.4; 95% confidence interval, 1.9-37.2; P =
      0.005]. CONCLUSIONS: This study supports the clinical utility of identification
      of UGT1A1 promoter polymorphisms before LV5FU2 + CPT-11 treatment to predict
      early hematologic toxicity. The -3156G>A polymorphism seems to be a better
      predictor than the UGT1A1 (TA)(6)TAA>(TA)(7)TAA polymorphism.

PMID- 17510209
TI  - N-ethylmaleimide-sensitive factor regulates beta2 adrenoceptor trafficking and
      signaling in cardiomyocytes.
AB  - Recycling of G protein-coupled receptors determines the functional
      resensitization of receptors and is implicated in switching beta2 adrenoceptor
      (beta2AR) G protein specificity in cardiomyocytes. The human beta2AR carboxyl end
      binds to the N-ethylmaleimide-sensitive factor (NSF), an ATPase integral to
      membrane trafficking machinery. It is interesting that the human beta2AR
      (hbeta2AR) carboxyl end pulled down NSF from mouse heart lysates, whereas the
      murine one did not. Despite this difference, both beta2ARs exhibited substantial
      agonist-induced internalization, recycling, and Gi coupling in cardiomyocytes.
      The hbeta2AR, however, displayed faster rates of agonist-induced internalization
      and recycling compared with the murine beta2AR (mbeta2AR) and a more profound Gi
      component in its contraction response. Replacing the mbeta2AR proline (-1) with a
      leucine generated a gain-of-function mutation, mbeta2AR-P417L, with a rescued
      ability to bind NSF, faster internalization and recycling than the mbeta2AR, and
      a significant enhancement in Gi signaling, which mimics the hbeta2AR. Selective
      disruption of the mbeta2AR-P417L binding to NSF inhibited the receptor coupling
      to Gi. Mean-while, inhibiting NSF with N-ethylmaleimide blocked the mbeta2AR
      recycling after agonist-induced endocytosis. Expressing the NSF-E329Q mutant
      lacking ATPase activity inhibited the mbeta2AR coupling to Gi in cardiomyocytes.
      Our results revealed a dual regulation on hbeta2AR trafficking and signaling by
      NSF through direct binding to cargo receptor and its ATPase activity and
      uncovered an unprecedented role for the receptor binding to NSF in regulating G
      protein specificity that has diverged between mouse and human beta2ARs.

PMID- 17510210
TI  - Filamin B mutations cause chondrocyte defects in skeletal development.
AB  - Filamin B (FLNB) is a cytoplasmic protein that regulates the cytoskeletal network
      by cross-linking actin, linking cell membrane to the cytoskeleton and regulating
      intracellular signaling pathways responsible for skeletal development (Stossel,
      T.P., Condeelis, J., Cooley, L., Hartwig, J.H., Noegel, A., Schleicher, M. and
      Shapiro, S.S. (2001) Filamins as integrators of cell mechanics and signalling.
      Nat. Rev. Mol. Cell Biol., 2, 138-145). Mutations in FLNB cause human skeletal
      disorders [boomerang dysplasia, spondylocarpotarsal (SCT), Larsen, and
      atelosteogenesis I/III syndromes], which are characterized by disrupted vertebral
      segmentation, joint formation and endochondral ossification [Krakow, D.,
      Robertson, S.P., King, L.M., Morgan, T., Sebald, E.T., Bertolotto, C., Wachsmann
      Hogiu, S., Acuna, D., Shapiro, S.S., Takafuta, T. et al. (2004) Mutations in the
      gene encoding filamin B disrupt vertebral segmentation, joint formation and
      skeletogenesis. Nat. Genet., 36, 405-410; Bicknell, L.S., Morgan, T., Bonafe, L.,
      Wessels, M.W., Bialer, M.G., Willems, P.J., Cohn, D.H., Krakow, D. and Robertson,
      S.P. (2005) Mutations in FLNB cause boomerang dysplasia. J. Med. Genet., 42,
      e43]. Here we show that Flnb deficient mice have shortened distal limbs with
      small body size, and develop fusion of the ribs and vertebrae, abnormal spinal
      curvatures, and dysmorphic facial/calvarial bones, similar to the human
      phenotype. Characterization of the mutant mice demonstrated increased apoptosis
      along the bone periphery of the distal appendages, consistent with reduced bone
      width. No changes in the initial proliferative rate of chondrocytes were
      observed, but the progressive differentiation of chondrocyte precursors was
      impaired, consistent with reduced bone length. The extracellular matrix appeared
      disrupted and phosphorylated beta1-integrin (a collagen receptor and Flnb binding
      partner) expression was diminished in the mutant growth plate. Like integrin
      deficient chondrocytes, adhesion to the ECM was decreased in Flnb(-/-)
      chondrocytes, and inhibition of beta1-integrin in these cells led to further
      impairments in cell spreading. These data suggest that disruption of the ECM
      beta1-integrin-Flnb pathway contributes to defects in vertebral and distal limb
      development, similar to those seen in the human autosomal recessive SCT due to
      Flnb mutations.

PMID- 17510211
TI  - EGFR regulates RhoA-GTP dependent cell motility in E-cadherin mutant cells.
AB  - Gastric cancer associated E-cadherin germline missense mutations lead to
      significant functional consequences, in both the structural and signalling
      properties of the protein. In this study, we have characterized the effect of
      four E-cadherin germline missense mutations (T340A, A634V, P799R and V832M) in
      the interaction with the epidermal growth factor receptor (EGFR). We challenged
      the hypothesis that E-cadherin mutations perturb its ability to bind to EGFR,
      leading to constitutional activation of the EGFR, triggering activation of
      downstream effectors. We verified that missense mutations localized in the
      extracellular domain of the protein (T340A and A634V) exhibited reduced stability
      of the EGFR/E-cadherin heterodimers in contrast to germline mutations localized
      at the cytoplasmatic domain of the protein (P799R and V832M). We observed that
      cells expressing E-cadherin extracellular mutants displayed increased levels of
      phosphorylated EGFR upon ligand stimulation, when compared with cells expressing
      wild-type E-cadherin or intracellular mutants. We showed that upon treatment of E
      cadherin extracellular mutant cells with the EGFR inhibitor, the increase of RhoA
      activation is abrogated and accompanied by decreased migratory behaviour,
      supporting the idea that Rho-like proteins are EGFR downstream effectors. Our
      results bring new insights into the understanding of the distinct in vitro
      behaviours observed for E-cadherin missense mutations localized in different
      domains of the protein. Furthermore, we demonstrate that E-cadherin-dependent
      EGFR activation contributes to enhanced cell motility, in a mechanism involving
      RhoA activation.

PMID- 17510212
TI  - Common genetic variants and haplotypes in renal CLCNKA gene are associated to
      salt-sensitive hypertension.
AB  - Abnormal renal reabsorption of sodium (Na(+)) is likely to play a role in the
      pathogenesis of salt-sensitivity. In the kidney, chloride channels CLC-Ka (gene
      CLCNKA) and CLC-Kb (gene CLCNKB) and their subunit Barttin (gene BSND) have
      important effects on the control of Na(+) and water homeostasis. We investigated
      if single nucleotide polymorphisms (SNPs) or haplotypes within CLCNKA, CLCNKB and
      BSND loci affect salt-sensitivity in hypertensive subjects. Associations between
      blood pressure (BP) change after Na(+)-load and 15 SNPs spanning the length of
      CLCNKA and CLCNKB and six SNPs spanning the length of BSND were studied in 314
      never treated essential hypertensives who underwent an i.v. infusion of saline
      (300 mm NaCl in 2 l H(2)O in 120 min). Four SNPs were significantly associated
      with BP change after Na-load. Rs848307 (P = 0.0026) and rs1739843 (P = 0.0023)
      map upstream the 5' of CLCNKA. Non-coding Rs1010069 (P = 0.0006) and non
      synonymous rs1805152 (Thr447Ala; P = 0.0078) map within CLCNKA. Moreover, basal
      plasma renin activity and heart rate (measured before Na-load) were significantly
      lower in patients carrying the alleles associated with the larger mean BP
      increase after Na-load, indicating that such alleles are associated with chronic
      volume expansion. This study supports the candidacy of CLCNKA as a new
      susceptibility gene for salt-sensitivity.

PMID- 17510213
TI  - Lotus tenuis tolerates the interactive effects of salinity and waterlogging by
      'excluding' Na+ and Cl- from the xylem.
AB  - Salinity and waterlogging interact to reduce growth of poorly adapted species by,
      amongst other processes, increasing the rate of Na(+) and Cl(-) transport to
      shoots. Xylem concentrations of these ions were measured in sap collected using
      xylem-feeding spittlebugs (Philaenus spumarius) from Lotus tenuis and Lotus
      corniculatus in saline (NaCl) and anoxic (stagnant) treatments. In aerated NaCl
      solution (200 mM), L. corniculatus had 50% higher Cl(-) concentrations in the
      xylem and shoot compared with L. tenuis, whereas concentrations of Na(+) and K(+)
      did not differ between the species. In stagnant-plus-NaCl solution, xylem Cl(-)
      and Na(+) concentrations of L. corniculatus increased to twice those of L.
      tenuis. These differences in xylem ion concentrations, which were not caused by
      variation in transpiration between the two species, contributed to lower net
      accumulation of Na(+) and Cl(-) in shoots of L. tenuis, indicating that ion
      transport mechanisms in roots of L. tenuis were contributing to better
      'exclusion' of Cl(-) and Na(+) from shoots, compared with L. corniculatus. Root
      porosity was also higher in L. tenuis, due to constitutive aerenchyma, than in L.
      corniculatus, suggesting that enhanced root aeration contributed to the
      maintenance of Na(+) and Cl(-) 'exclusion' in L. tenuis exposed to stagnant-plus
      NaCl treatment. Lotus tenuis also had greater dry mass than L. corniculatus after
      56 d in NaCl or stagnant-plus-NaCl treatment. Thus, Cl(-) 'exclusion' is a key
      trait contributing to salt tolerance of L. tenuis, and 'exclusion' of both Cl(-)
      and Na(+) from the xylem enables L. tenuis to tolerate, better than L.
      corniculatus, the interactive stresses of salinity and waterlogging.

PMID- 17510214
TI  - Rho inhibition induces migration of mesenchymal stromal cells.
AB  - Although mesenchymal stromal cells (MSCs) are being increasingly used as cell
      therapeutics in clinical trials, the mechanisms that regulate their chemotactic
      migration behavior are incompletely understood. We aimed to better define the
      ability of the GTPase regulator of cytoskeletal activation, Rho, to modulate
      migration induction in MSCs in a transwell chemotaxis assay. We found that
      culture-expanded MSCs migrate poorly toward exogenous phospholipids
      lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) in transwell
      assays. Moreover, plasma-induced chemotactic migration of MSCs was even inhibited
      after pretreatment with LPA. LPA treatment activated intracellular Rho and
      increased actin stress fibers in resident MSCs. Very similar cytoskeletal changes
      were observed after microinjection of a cDNA encoding constitutively active RhoA
      (RhoAV14) in MSCs. In contrast, microinjection of cDNA encoding Rho inhibitor C3
      transferase led to resolution of actin stress fibers, appearance of a looser
      actin meshwork, and increased numbers of cytoplasmic extensions in the MSCs.
      Surprisingly, in LPA-pretreated MSCs migrating toward plasma, simultaneous
      addition of Rho inhibitor C2I-C3 reversed LPA-induced migration suppression and
      led to improved migration. Moreover, addition of Rho inhibitor C2I-C3 resulted in
      an approximately 3- to 10-fold enhancement of chemotactic migration toward LPA,
      S1P, as well as platelet-derived growth factor or hepatocyte growth factor. Thus,
      inhibition of Rho induces rearrangement of actin cytoskeleton in MSCs and renders
      them susceptible to induction of migration by physiological stimuli. Disclosure
      of potential conflicts of interest is found at the end of this article.

PMID- 17510215
TI  - Directed sibling cord blood banking for transplantation: the 10-year experience
      in the national blood service in England.
AB  - Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for
      transplantation. Although UCB is often collected from unrelated donors, directed
      umbilical cord blood (DCB) from sibling donors also provides an important source
      of UCB for transplantation. This report summarizes the experience in collection,
      testing, storage, and transplantation of DCB units by the National Blood Service
      for England and North Wales over 10 years. Eligibility for collection was based
      on an existing sibling suffering from a disease that may be treated by stem cell
      transplantation or a family history that could result in the birth of a sibling
      with a disease that could be treated by stem cell transplantation. Collections
      were made on the provision that the sibling's clinician was willing to
      financially support the collection and to take responsibility for medical review
      of the mother and potential recipient. Given the high investment in UCB banking
      and the introduction of new regulations and mandatory licensing under the
      European Union Tissues and Cells Directive and those proposed in the U.S., this
      report details the procedures that we have used for DCB donations, the outcome
      data where donations have been used for transplantation, and it provides some
      timely recommendations for best practices. Disclosure of potential conflicts of
      interest is found at the end of this article.

PMID- 17510216
TI  - Concise review: Telomere biology in normal and leukemic hematopoietic stem cells.
AB  - The measurement of telomere length can give an insight into the replicative
      history of the cells in question. Much of the observed telomere loss occurs at
      the stem and progenitor cell level, even though these populations express the
      enzyme telomerase. Telomerase-transfected hematopoietic stem cells (HSC),
      although able to maintain telomere length, are still limited in terms of ability
      to undergo sequential transplantation, and other factors require to be addressed
      to achieve optimal levels of stem cell expansion. Unchecked telomere loss by HSC,
      meanwhile, would appear to play a significant role in the pathogenesis of bone
      marrow failure, as observed in the condition dyskeratosis congenita. This
      heterogeneous inherited condition appears to exhibit telomerase dysfunction as a
      common final pathogenic mechanism. Although less well-established for acquired
      marrow failure syndromes, mutations in key telomerase components have been
      described. The identification of the leukemic stem cell (LSC), along with the
      desire to target this population with anti-leukemia therapy, demands that
      telomerase biology be fully understood in this cell compartment. Future studies
      using primary selected LSC-rich samples are required. A better understanding of
      telomerase regulation in this population may allow effective targeting of the
      telomerase enzyme complex using small molecule inhibitors or additional novel
      approaches. Disclosure of potential conflicts of interest is found at the end of
      this article.

PMID- 17510217
TI  - Generation of insulin-producing islet-like clusters from human embryonic stem
      cells.
AB  - Recent success in pancreatic islet transplantation has energized the field to
      discover an alternative source of stem cells with differentiation potential to
      beta cells. Generation of glucose-responsive, insulin-producing beta cells from
      self-renewing, pluripotent human ESCs (hESCs) has immense potential for diabetes
      treatment. We report here the development of a novel serum-free protocol to
      generate insulin-producing islet-like clusters (ILCs) from hESCs grown under
      feeder-free conditions. In this 36-day protocol, hESCs were treated with sodium
      butyrate and activin A to generate definitive endoderm coexpressing CXCR4 and
      Sox17, and CXCR4 and Foxa2. The endoderm population was then converted into
      cellular aggregates and further differentiated to Pdx1-expressing pancreatic
      endoderm in the presence of epidermal growth factor, basic fibroblast growth
      factor, and noggin. Soon thereafter, expression of Ptf1a and Ngn3 was detected,
      indicative of further pancreatic differentiation. The aggregates were finally
      matured in the presence of insulin-like growth factor II and nicotinamide. The
      temporal pattern of pancreas-specific gene expression in the hESC-derived ILCs
      showed considerable similarity to in vivo pancreas development, and the final
      population contained representatives of the ductal, exocrine, and endocrine
      pancreas. The hESC-derived ILCs contained 2%-8% human C-peptide-positive cells,
      as well as glucagon- and somatostatin-positive cells. Insulin content as high as
      70 ng of insulin/mug of DNA was measured in the ILCs, representing levels higher
      than that of human fetal islets. In addition, the hESC-derived ILCs contained
      numerous secretory granules, as determined by electron microscopy, and secreted
      human C-peptide in a glucose-dependent manner. Disclosure of potential conflicts
      of interest is found at the end of this article.

PMID- 17510218
TI  - Effects of HOXB4 overexpression on ex vivo expansion and immortalization of
      hematopoietic cells from different species.
AB  - Overexpression of the human HOXB4 has been shown to induce the expansion and self
      renewal of murine hematopoietic stem cells. In preparation for clinical studies,
      we wished to investigate the effects of HOXB4 on cells from other species, in
      particular preclinical large animals such as dogs and nonhuman primates. Thus, we
      transduced CD34(+) cells from nonhuman primates, dogs, and humans with a HOXB4
      expressing gammaretroviral vector and a yellow fluorescent protein-expressing
      control vector. Compared with the control vector, HOXB4 overexpression resulted
      in a much larger increase in colony-forming cells in dog cells (28-fold) compared
      with human peripheral blood, human cord blood, and baboon cells (two-, four-, and
      fivefold, respectively). Furthermore, we found that HOXB4 overexpression resulted
      in immortalization with sustained growth (>12 months) of primitive hematopoietic
      cells from mice and dogs but not from monkeys and humans. This difference
      correlated with increased levels of retrovirally overexpressed HOXB4 in dog and
      mouse cells compared with human and nonhuman primate cells. The immortalized
      cells did not show any evidence of insertional mutagenesis or chromosomal
      abnormalities. Competitive congenic transplantation experiments showed that HOXB4
      expanded mouse cells engrafted well after 1 or 3 months of expansion, and no
      leukemia was observed in mice. Our findings suggest that the growth promoting
      effects of HOXB4 are critically dependent on HOXB4 expression levels and that
      this can result in important species-specific differences in potency. Disclosure
      of potential conflicts of interest is found at the end of this article.

PMID- 17510219
TI  - Increased dentate neurogenesis after grafting of glial restricted progenitors or
      neural stem cells in the aging hippocampus.
AB  - Neurogenesis in the dentate gyrus (DG) declines severely by middle age,
      potentially because of age-related changes in the DG microenvironment. We
      hypothesize that providing fresh glial restricted progenitors (GRPs) or neural
      stem cells (NSCs) to the aging hippocampus via grafting enriches the DG
      microenvironment and thereby stimulates the production of new granule cells from
      endogenous NSCs. The GRPs isolated from the spinal cords of embryonic day 13.5
      transgenic F344 rats expressing human alkaline phosphatase gene and NSCs isolated
      from embryonic day 9 caudal neural tubes of Sox-2:EGFP transgenic mice were
      expanded in vitro and grafted into the hippocampi of middle-aged (12 months old)
      F344 rats. Both types of grafts survived well, and grafted NSCs in addition
      migrated to all layers of the hippocampus. Phenotypic characterization revealed
      that both GRPs and NSCs differentiated predominantly into astrocytes and
      oligodendrocytic progenitors. Neuronal differentiation of graft-derived cells was
      mostly absent except in the dentate subgranular zone (SGZ), where some of the
      migrated NSCs but not GRPs differentiated into neurons. Analyses of the numbers
      of newly born neurons in the DG using 5'-bromodeoxyuridine and/or doublecortin
      assays, however, demonstrated considerably increased dentate neurogenesis in
      animals receiving grafts of GRPs or NSCs in comparison with both naive controls
      and animals receiving sham-grafting surgery. Thus, both GRPs and NSCs survive
      well, differentiate predominantly into glia, and stimulate the endogenous NSCs in
      the SGZ to produce more new dentate granule cells following grafting into the
      aging hippocampus. Grafting of GRPs or NSCs therefore provides an attractive
      approach for improving neurogenesis in the aging hippocampus. Disclosure of
      potential conflicts of interest is found at the end of this article.

PMID- 17510220
TI  - Mesenchymal stem cells inhibit the differentiation of dendritic cells through an
      interleukin-6-dependent mechanism.
AB  - Mesenchymal stem cells (MSC) are of particular interest for their potential
      clinical use in tissue engineering as well as for their capacity to reduce the
      incidence and severity of graft-versus-host disease in allogeneic
      transplantation. We have previously shown that MSC-mediated immune suppression
      acts via the secretion of soluble factor(s) induced upon stimulation. The aim of
      this study was to identify the molecule(s) involved and the underlying
      mechanism(s). We show that murine MSC secrete high levels of interleukin (IL)-6
      and vascular endothelial growth factor, which are directly correlated to the
      inhibition of T-cell proliferation. The T-cell activation is partially restored
      upon addition of a neutralizing anti-IL-6 antibody or the prostaglandin E2
      inhibitor indomethacin. Interestingly, no indoleamine 2,3-dioxygenase activity
      was detected in our conditions. Instead, we show that MSC reduce the expression
      of major histocompatibility complex class II, CD40, and CD86 costimulatory
      molecules on mature dendritic cells (DC), which was responsible for a decrease in
      T-cell proliferation. Moreover, we show that the differentiation of bone marrow
      progenitors into DC cultured with conditioned supernatants from MSC was partly
      inhibited through the secretion of IL-6. Altogether, these data suggest that IL-6
      is involved in the immunoregulatory mechanism mediated by MSC through a partial
      inhibition of DC differentiation but is probably not the main mechanism.
      Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 17510221
TI  - Executive management and IT innovation in health: identifying the barriers to
      adoption.
AB  - This study aims to understand IT investment decisions from the perspective of
      senior health system executives. A two-stage study was used to investigate this
      highly influential, very specialized and small population of interest. The first
      stage involved qualitative interviews with top health executives and analysed
      their opinions and beliefs using an innovation diffusion theory framework. The
      second stage involved quantitative surveys of senior health executives to gain an
      understanding of their opinions regarding the organizational and technological
      drivers (the independent variables) and the level of IT adoption (the dependent
      variable). It was found that the majority of drivers identified as being
      significant to organizational and technological innovation are degraded in
      respect to IT and health. It was concluded that health executives hold a range of
      views that potentially inhibit the increased adoption of IT in health. In
      particular, beliefs about the technology itself have been identified as the most
      influential deterrents.

PMID- 17510222
TI  - Competencies for graduate curricula in health, medical and biomedical
      informatics: a framework.
AB  - The rapid emergence of programmes in health informatics, medical informatics and
      biomedical informatics implies a need for core curricula in these diverse
      disciplines. This study investigated the recommended competencies for health and
      medical informatics, aiming to develop a framework for use in curricular
      development. Current health and medical programmes around the world were analysed
      to assess how these competencies are reflected in current curricula and to
      identify new competencies. Several preferred skills and knowledge sets were
      identified and 40 programs were analysed. Diverse curricular designs were found
      in these programmes. Competencies such as research skills, knowledge in health
      information systems and methods for informatics/computer science were the most
      frequently taught. Knowledge or skills in interpersonal communications, social
      impact of IT on health, and data mining may represent important skills for future
      informaticians. The suggested framework and the data analysed may be important
      for developing a competency-based modular curriculum.

PMID- 17510223
TI  - The influence of electronic medical record usage on nonverbal communication in
      the medical interview.
AB  - This study examined nonverbal communication in relation to electronic medical
      record (EMR) use during the medical interview. Six physicians were videotaped
      during their consultations with 50 different patients at a single setting
      Veterans Administration Hospital. Three different office spatial designs were
      identified and named 'open,' 'closed' and 'blocked'. The ;open' arrangement put
      physicians in a position to establish better eye contact and physical orientation
      than did the alternative 'closed' and 'blocked' office configurations. Physicians
      who accessed the EMR and took 'breakpoints' (short periods of no computer use and
      sustained eye contact with patients) used more nonverbal cues than physicians who
      tended to talk with their patients while continuously working on the computer.
      Long pauses in conversational turn taking associated with EMR use may have
      positively influenced doctor-patient communication. High EMR use interviews were
      associated with patients asking more questions than they did in low EMR use
      interviews. Implications for medical education and future research are discussed.

PMID- 17510224
TI  - Barriers to the adoption of electronic health records: using concept mapping to
      develop a comprehensive empirical model.
AB  - The study attempts to unify prior research and develop a comprehensive,
      empirically based conceptual model of the barriers to EHR adoption among
      community physicians. The model uses concept mapping, which taps the shared
      expertise of a group and provides reliable estimates with relatively small sample
      sizes. The methodology includes brainstorming of barrier statements and sorting
      and rating of issue statements. The model illuminates the larger structure of
      barriers as well as the finer details of constituent issues. Core issues are
      standardization and interoperability; also important are technical issues and the
      cost-benefit of adopting EHRs. However, psychosocial issues, the main focus of
      diffusion research, seem relatively peripheral. We believe the development of
      this model is an important first step in creating effective and measurable
      interventions that enhance the adoption of EHRs in healthcare.

PMID- 17510225
TI  - Developing services for head injury: obtaining the data.
AB  - The aim of this article is to propose standards for data collection in head
      injury, the commonest cause of death and disability in young people. The
      objectives include evaluation of an audit methodology. The retrospective review
      conducted for the Eastern Head Injury Study in the UK identified a variety of
      problems, notably ambiguous terminology, inadequacies in ICD-10 codes, and
      inconsistent practices in recording data on head injury. Conclusions are that the
      standards developed through the review should improve data collection practice,
      and rehabilitation codes should assist in tracking patient pathways through care.

PMID- 17510226
TI  - The impact of electronic patient records on workflow in general practice.
AB  - The Patient Access to Electronic Healthcare Records System (PAERS) allows
      patients to register their arrival at a GP's surgery and to view their healthcare
      record electronically whilst in the waiting area. The research reported in this
      short article was carried out to identify potential changes in clinical and
      administrative workflow resulting from the introduction of the system. The study
      considers workflow pre and post the implementation of PAERS. It also makes
      comparisons between two UK London-based surgeries, one with PAERS (Wells Park
      Practice) and one without such a system (South Lewisham Group Practice). The
      impact of PAERS on workflow and the potential benefits for GPs, administrative
      staff and patients are highlighted.

PMID- 17510227
TI  - Career-ending injuries to professional jockeys in British horse racing (1991
      2005).
AB  - BACKGROUND: It has been previously shown that professional jump and flat racing
      jockeys suffer a high incidence of injury as a consequence of their profession.
      This paper specifically examines career-ending injuries to professional jockeys
      in Great Britain. AIMS: To investigate career-ending injuries in professional
      jockeys. METHOD: Analysis of prospectively collected injury database on
      professional jockeys. RESULTS: The majority of injuries in this study occurred to
      the head, shoulder or torso. Fractures were the most common type of injury that
      led to a decision to end a career, followed by neurological injury to the head
      and/or spine. CONCLUSION: Injuries to the head are the most common career-ending
      injuries, and consideration of injury counter measures could be an important
      strategy in equestrian sports.

PMID- 17510228
TI  - Medical report from the 2006 FIFA World Cup Germany.
AB  - OBJECTIVE: To continue the injury surveillance of FIFA-sponsored football
      tournaments and report on other medical aspects of the 2006 FIFA World Cup.
      DESIGN: Prospective epidemiological injury surveillance and descriptive summary
      of additional medical aspects. SETTING: Major international football tournament.
      PARTICIPANTS: National team players, doctors and referees at the 2006 FIFA World
      Cup Germany. MAIN OUTCOME MEASURES: Injury type, location and rate. RESULTS: 145
      injuries were reported for the 64 matches of the 2006 FIFA World Cup Germany-an
      overall injury rate of 68.7 per 1000 match hours (95% CI 57.5 to 79.9) or 2.3
      injuries per match, in comparison with 2.7 injuries per match in the 2002 FIFA
      World Cup (p = NS). Physical examinations before participation uncovered no
      hidden cardiovascular problems. Once the tournament started, no referees were
      unable to complete their duties. There were no positive doping tests.
      CONCLUSIONS: The injury rate for this World Cup was below that of 2002, but
      consistent with the overall injury rate per match since data collection began in
      1998. There continues to be no evidence of systematic doping in international
      football.

PMID- 17510229
TI  - Effect of static stretching of muscles surrounding the knee on knee joint
      position sense.
AB  - BACKGROUND: Muscle stretching is widely used in sport training and in
      rehabilitation. Considering the important contribution of joint position sense
      (JPS) to knee joint stability and function, it is legitimate to question if
      stretching might alter the knee JPS. OBJECTIVE: To evaluate if a stretch regimen
      consisting of three 30 s stretches alters the knee JPS. DESIGN AND SETTING: A
      blinded, randomised design with a washout time of 24 h was used. SUBJECTS: 39
      healthy students (21 women, 18 men) volunteered to participate in this study.
      METHODS AND MAIN OUTCOME MEASURES: JPS was estimated by the ability to reproduce
      the two target positions (20 degrees and 45 degrees of flexion) in the dominant
      knee. The absolute angular error (AAE) was defined as the absolute difference
      between the target angle and the subject perceived angle of knee flexion. AAE
      values were measured before and immediately after the static stretch.
      Measurements were repeated three times. The static stretch comprised a 30 s
      stretch followed by a 30 s pause, three times for each muscle. RESULTS: The AAE
      decreased significantly after the stretching protocols for quadriceps (3.5 (1.3)
      vs 0.7 (2.4); p<0.001), hamstring (3.6 (2.2) vs 1.6 (3.1); p = 0.016) and
      adductors (3.7 (2.8) vs 1.7 (2.4); p = 0.016) in 45 degrees of flexion, but no
      differences were found for values of the gastrocnemius and popliteus muscles in
      this angle and for the values of all muscles in 20 degrees of flexion (p>0.05).
      CONCLUSION: The accuracy of the knee JPS in 45 degrees of flexion is improved
      subsequent to a static stretch regimen of quadriceps, hamstring and adductors in
      healthy subjects.

PMID- 17510230
TI  - Salbutamol exhibits androgenic activity in vitro.
AB  - BACKGROUND: Salbutamol has been shown to mediate anabolic effects after
      intravenous administration. However, the mechanism responsible for the anabolic
      actions of salbutamol remains unknown. AIM: To investigate the potential
      mechanism by which salbutamol mediates anabolic effects in vitro. METHODS: The
      potential androgenic activity of salbutamol was investigated in vitro by the A
      Screen assay that measures androgen-dependent inhibition of proliferation of the
      androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1.
      RESULTS: The assay was validated with three known androgens; methyltrienolone
      (R1881), 5alpha-dihydrotestosterone (DHT) and danazol. IC50 values of R1881, DHT
      and danazol, 4.41x10(-11), 4.44x10(-11) and 1.08x10(-8) M, respectively, were in
      the ranges known from earlier studies. Our results demonstrate that salbutamol
      exhibits androgenic activity, with an IC50 value of 8.93x10(-6) M. Anti
      estrogenic or cytotoxic effects, which might have interfered with the assay, were
      excluded by additional experiments on wild-type MCF7 and MCF7-AR1 cells,
      respectively. CONCLUSION: These data indicate that salbutamol exerts anabolic
      effects through androgen receptor agonistic activity in vitro.

PMID- 17510231
TI  - Caveolae nitration of Janus kinase-2 at the 1007Y-1008Y site: coordinating
      inflammatory response and metabolic hormone readjustment within the somatotropic
      axis.
AB  - Life-threatening proinflammatory response (PR) induces severe GH resistance.
      Although low-level PR is much more commonly encountered clinically, relatively
      few studies have investigated the accompanying change in GH signal transduction
      progression and, in particular, the impact of low-level PR on Janus kinase (JAK)
      2. Using a low-level, in vivo endotoxin [lipopolysaccharide (LPS)] challenge
      protocol, we demonstrated that the liver tissue content of JAK2 declined 24 h
      (62%, P < 0.02) after LPS and that tyrosine-nitrated JAK2 could be
      immunoprecipitated from post-LPS liver biopsy homogenates. With antibodies
      developed to probe specifically for nitration at the (1007)Y-(1008)Y
      phosphorylation epitope of JAK2, we demonstrated that the nitrated (1007)Y
      (1008)Y-JAK-2 (nitro-JAK2) coimmunoprecipitated with caveolin-1 and (1177)phospho
      SER-endothelial nitric oxide synthase when post-LPS liver homogenates were
      treated with anticaveolin-1 and protein A/G. The magnitude of increase in nitro
      JAK2 was attenuated in animals treated with vitamin E prior to LPS. The increase
      in nitro-JAK2 after LPS was greater in a line of experimental animals with a
      genetic propensity for higher PR at the given LPS dose than responses measured in
      their normal counterparts. The development and remission of nitro-JAK2 was
      temporally concordant with changes in plasma concentrations of IGF-I;
      hepatocellular IGF-I mRNA content was inversely proportional to nitro-JAK2
      content. Localized changes in the state of nitration of regulatory
      phosphorylation domains of JAK2 in caveolar microenvironments and tissue content
      of JAK2 during PR suggest a unique mechanism through which discrete signal
      transduction switching might occur in the liver to fine tune cellular responses
      to the endocrine-immune signals that develop during low-level, transient
      proinflammatory stress.

PMID- 17510232
TI  - Growth hormone (GH)-associated nitration of Janus kinase-2 at the 1007Y-1008Y
      epitope impedes phosphorylation at this site: mechanism for and impact of a GH,
      AKT, and nitric oxide synthase axis on GH signal transduction.
AB  - A generalized increase in liver protein tyrosine nitration (3'-nitrotyrosine, 3'
      NT) occurs after GH injection in a time frame consistent with observed acute GH
      hyporesponsiveness. Here we investigated whether the GH-associated nitration
      process might be targeted to the (1007)Y-(1008)Y-phosphorylation epitope of Janus
      kinase (JAK)-2 because of its homology to a defined peptide nitration motif.
      Using antibodies we developed to the 3'NT-substituted peptide analog of the
      (1007)Y-(1008)Y-JAK2 site (nitro-JAK2), we demonstrated a rapid increase in
      membrane-associated nitro-JAK2 after GH. In vivo (bovine liver) and in vitro
      (porcine hepatocytes), GH-induced cellular levels of nitro-(1007)Y-(1008)Y-JAK2
      persisted significantly longer after a stimulatory GH pulse than did levels of
      phospho-JAK2. Treatment of cultured cells with inhibitors of AKT or endothelial
      nitric oxide synthase prior to GH challenge attenuated the increases in nitro
      JAK2 predominantly in the membrane subcellular fraction. In instances in which GH
      effected orthophosphorylation of (694)Y-signal transducer and activator of
      transcription (STAT)-5b, the addition of AKT and endothelial nitric oxide
      synthase inhibitors prior to GH significantly increased the levels of phospho
      (694)Y-STAT5b and phospho-(1007)Y-JAK2 over those arising from GH alone. Nuclear
      magnetic resonance molecular modeling of natural and 3'-NT- and orthophosphate
      substituted peptide analogs of the (1007)Y-(1008)Y site demonstrated significant
      effects of 3'-nitration on the planar orientation and intramolecular stabilizing
      points of the affected tyrosines. When these peptides were used as substrates for
      in vitro tyrosine kinase phosphorylation reactions, 3'-NT in the (1007)Y and/or
      (1008)Y positions blocked the generation of (1007)Y-phosphotyrosine. The data
      suggest that the nitration of JAK2 may act as an inhibitory counterpart to
      phosphorylation activation, reflecting a very localized break on the progression
      of GH signal transduction processes spanning JAK-STAT-AKT interactions.

PMID- 17510234
TI  - Effects of granulosa cell-specific deletion of Rb in Inha-alpha null female mice.
AB  - Our laboratory is interested in the gonadal growth regulatory properties of
      inhibins, members of the TGFbeta superfamily. We have previously shown that
      female mice lacking inhibins (Inha(-/-)) develop granulosa cell tumors and that
      concurrent loss of p27 accelerates tumor development. It has also been shown that
      the retinoblastoma protein RB regulates the G(1) to S phase transition of the
      cell cycle by controlling the activity of transcription factors and stabilizing
      the levels of the cell cycle inhibitor P27. Based on these data, we hypothesized
      that concurrent loss of Rb and inhibins in the ovary will exacerbate tumor
      formation. To test this hypothesis, we generated an ovarian granulosa cell
      conditional knockout (cKO) of Rb using the Cre/lox recombination system in the
      background of Inha(-/-) mice. Inha(-/-)/Rb cKO females show a modest increase in
      mortality rates compared with Inha(-/-) females. Although histologically similar
      to Inha(-/-) ovarian tumors, tumors from Inha(-/-)/Rb cKO females show increased
      number of mitotic figures and apoptotic rates. Interestingly, P27 levels are
      decreased in Inha(-/-)/Rb cKO ovarian tumors, likely due to the combined effect
      of Rb loss and increased Skp2 expression, which targets P27 to the proteosome. We
      propose that Rb loss may cause cell cycle delay or arrest, followed by apoptosis
      and that increases in p107 and p130 levels may compensate for Rb loss. These
      findings confirm the importance of P27 as a cell cycle regulator in granulosa
      cells and suggest functional compensation between RB-like proteins in ovarian
      tumorigenesis.

PMID- 17510233
TI  - Sex difference in link between interleukin-6 and stress.
AB  - Inflammation contributes to disease development, and the neuroimmunoendocrine
      interface is a potential site of action for inflammatory products like IL-6 to
      affect health. Although plasma IL-6 can stimulate the activity of the hypothalamo
      pituitary-adrenocortical (HPA) axis, the precise role, if any, for IL-6 in the
      HPA response to nonimmunological stressors is unclear. The purpose of this study
      was to test the hypothesis that IL-6 in the stalk median eminence (SME) can be
      directly involved in stimulating ACTH secretion in response to acute stress in
      female swine. This study was undertaken as a result of finding IL-6 localized to
      the external zone of the SME next to the hypophyseal portal vessels. Results
      indicate that content of IL-6 in the SME decreases in response to acute stress
      along with an increase in nuclear phosphorylated signal transducer and activator
      of transcription-3 (pSTAT-3) in pituitary corticotrophs and a simultaneous
      increase in plasma concentrations of IL-6 and ACTH. Furthermore, we show that
      females concomitantly display greater SME content of IL-6 and greater HPA
      responsiveness to stress, thereby suggesting that IL-6 release from the SME is an
      integral factor contributing to enhanced stress responsiveness in females. Our
      results provide evidence for a direct link between IL-6 and ACTH release and
      reveal a sex difference in this relationship.

PMID- 17510235
TI  - Steroid-mediated regulation of the epithelial sodium channel subunits in mammary
      epithelial cells.
AB  - The epithelial sodium channel (ENaC) is a key mediator of sodium transport in
      epithelia; however, little is known about ENaC expression in mammary epithelia.
      Using real-time PCR, we demonstrated the expression of the ENaC subunit mRNAs in
      mouse and human mammary cell lines and in vivo mouse mammary tissue. We
      determined the effects of glucocorticoids, progesterone, and prolactin on ENaC
      expression in four mammary cell lines. Dexamethasone induced all detectable ENaC
      subunits in noncancerous cell lines, HC11 and MCF10A. Interestingly, in cancerous
      cell lines (T-47D and MCF-7), both beta- and gamma- but not alphaENaC mRNAs were
      induced by dexamethasone. Progesterone induced ENaC mRNA only in T-47D cells, and
      prolactin had no effects. gammaENaC was rapidly induced by steroids, whereas
      induction of alpha- and betaENaC was slower; moreover, the induction of the beta
      subunit required de novo protein synthesis. Dexamethasone treatment did not
      affect ENaC mRNA stability. Western blot analysis revealed immunoreactive bands
      corresponding to different forms of alpha-, beta-, and gammaENaC; dexamethasone
      significantly increased the intensity of alphaENaC (85 kDa) and betaENaC (90
      kDa). We also showed an in vivo reduction in alphaENaC levels in the mammary
      tissue of lactating mice as compared with controls, whereas beta- and gammaENaC
      mRNA levels were significantly increased. Furthermore, dexamethasone in vivo
      significantly increased alpha-, beta-, and gammaENaC mRNA expression. Our data
      indicate that both mouse and human mammary cells express all ENaC subunits, and
      they are regulated by steroid hormones in a temporal and cell-specific manner
      both in culture and in vivo.

PMID- 17510236
TI  - Gene expression analysis of endometrium reveals progesterone resistance and
      candidate susceptibility genes in women with endometriosis.
AB  - The identification of molecular differences in the endometrium of women with
      endometriosis is an important step toward understanding the pathogenesis of this
      condition and toward developing novel strategies for the treatment of associated
      infertility and pain. In this study, we conducted global gene expression analysis
      of endometrium from women with and without moderate/severe stage endometriosis
      and compared the gene expression signatures across various phases of the
      menstrual cycle. The transcriptome analysis revealed molecular dysregulation of
      the proliferative-to-secretory transition in endometrium of women with
      endometriosis. Paralleled gene expression analysis of endometrial specimens
      obtained during the early secretory phase demonstrated a signature of enhanced
      cellular survival and persistent expression of genes involved in DNA synthesis
      and cellular mitosis in the setting of endometriosis. Comparative gene expression
      analysis of progesterone-regulated genes in secretory phase endometrium confirmed
      the observation of attenuated progesterone response. Additionally, interesting
      candidate susceptibility genes were identified that may be associated with this
      disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings
      provide a framework for further investigations on causality and mechanisms
      underlying attenuated progesterone response in endometrium of women with
      endometriosis.

PMID- 17510237
TI  - Peripheral infusion of insulin-like growth factor-I increases the number of
      newborn oligodendrocytes in the cerebral cortex of adult hypophysectomized rats.
AB  - We have previously shown that recombinant human (rh) IGF-I induces cell
      proliferation and neurogenesis in the hippocampus of hypophysectomized rats. In
      the current investigation, we determined the effects of rhIGF-I on proliferation
      and differentiation in the cerebral cortex. Adult hypophysectomized rats were
      injected with bromodeoxyuridine (BrdU) to label newborn cells (once a day for the
      first 5 d), and rhIGF-I was administered peripherally for 6 or 20 d. In the
      cerebral cortex, the number of BrdU-labeled cells increased after 20 d but not
      after 6 d of rhIGF-I infusion. This suggests that rhIGF-I enhances the survival
      of newborn cells in the cerebral cortex. Using BrdU labeling combined with the
      oligodendrocyte-specific markers myelin basic protein and 2',3'-cyclic nucleotide
      3'-phosphodiesterase, we demonstrated an increase in oligodendrogenesis in the
      cerebral cortex. The total amount of myelin basic protein and 2',3'-cyclic
      nucleotide 3'-phosphodiesterase was also increased on Western blots of
      homogenates of the cerebral cortex, confirming the immunohistochemical findings.
      Also, we observed an increase in the number of capillary-associated BrdU-positive
      cells, although total capillary area was not increased. rhIGF-I treatment did not
      affect cortical astrogliogenesis and neurogenesis was not observed. The ability
      of rhIGF-I to induce cortical oligodendrogenesis may have implications for the
      regenerative potential of the cortex.

PMID- 17510238
TI  - Transgenic male mice expressing human hydroxysteroid dehydrogenase 2 indicate a
      role for the enzyme independent of its action on sex steroids.
AB  - Hydroxysteroid (17beta) dehydrogenase 2 (HSD17B2) has been shown to inactivate
      both estrogens and androgens and activate 20alpha-hydroxyprogesterone to
      progesterone. In the present study, we generated transgenic (TG) mice
      ubiquitously expressing human HSD17B2. The TG mice produced showed growth
      retardation and delayed eye opening at the postnatal age. Disrupted
      spermatogenesis was evident in the presence of normal serum and intratesticular
      testosterone, progesterone, and normal circulating LH concentrations. A proper
      androgen action in the target tissues was confirmed by normal histological
      appearance of the prostate and epididymis. Furthermore, quantitative RT-PCR
      analysis indicated only a slight decrease in androgen-dependent gene expression
      in the prostate. The disrupted spermatogenesis was not associated with increased
      germ cell apoptosis as analyzed by caspase-3 activation. However, it resulted in
      infertility in the HSD17B2 TG males after the age of 3 months, and at the age of
      6 months the seminiferous tubules showed a Sertoli cell-only phenotype. The data
      indicate that the growth retardation and disrupted spermatogenesis are not due to
      a lack of proper estrogen or androgen action. Interestingly, the testicular
      phenotype and some of the other phenotypic changes described are typically
      observed in mice with reduced action of retinoic acid signaling. This, together
      with the rescue of the testis phenotype by a synthetic retinoic acid receptor
      agonist (4-[(E)-2-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)-1
      propenyl] benzoic acid), suggests a role for HSD17B2 in the action of retinoids,
      in addition to its oxidative HSD17B activity on sex steroids.

PMID- 17510239
TI  - Corticosterone inhibits the lipid-mobilizing effects of oleoyl-estrone in
      adrenalectomized rats.
AB  - Oleoyl-estrone (OE) is an adipose-derived signal that decreases energy intake and
      body lipid, maintaining energy expenditure and glycemic homeostasis.
      Glucocorticoids protect body lipid and the metabolic status quo. We studied the
      combined effects of OE and corticosterone in adrenalectomized female rats: daily
      OE gavages (0 or 10 nmol/g) and slow-release corticosterone pellets at four doses
      (0, 0.5, 1.7, and 4.8 mg/d). Intact and sham-operated controls were also
      included. After 8 d, body composition and plasma metabolites and hormones were
      measured. OE induced a massive lipid mobilization (in parallel with decreased
      food intake and maintained energy expenditure). Corticosterone increased fat
      deposition and inhibited the OE-elicited mobilization of body energy, even at the
      lowest dose. OE enhanced the corticosterone-induced rise in plasma
      triacylglycerols, and corticosterone blocked the OE-induced decrease in leptin.
      High corticosterone and OE increased insulin resistance beyond the effects of
      corticosterone alone. The presence of corticosterone dramatically affected OE
      effects, reversing its decrease of body energy (lipid) content, with little or no
      change on food intake or energy expenditure. The maintenance of glycemia and
      increasing insulin in parallel to the dose of corticosterone indicate a decrease
      in insulin sensitivity, which is enhanced by OE. The reversal of OE effects on
      lipid handling, insulin resistance, can be the consequence of a corticosterone
      induced OE resistance. Nevertheless, OE effects on cholesterol were largely
      unaffected. In conclusion, corticosterone administration effectively blocked OE
      effects on body lipid and energy balance as well as insulin sensitivity and
      glycemia.

PMID- 17510240
TI  - Differential regulation of hypoxia-inducible factor-1 through receptor tyrosine
      kinase transactivation in vascular smooth muscle cells.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a decisive element for the transcriptional
      regulation of many genes expressed in hypoxic conditions. In vascular smooth
      muscle cells, the vasoactive hormone angiotensin II (Ang II) is a very potent
      inducer and activator of HIF-1. As opposed to hypoxia, which induces HIF-1alpha
      by protein stabilization, Ang II induced HIF-1alpha through transcriptional and
      translational mechanisms. Interestingly, a number of intracellular signaling
      events triggered by Ang II are mediated by the transactivation of receptor
      tyrosine kinases. The major receptor tyrosine kinases shown to be transactivated
      by Ang II in vascular smooth muscle cells are the epidermal growth factor
      receptor and the IGF-I receptor. In this study, we demonstrate that the
      transactivation of both these receptor tyrosine kinases is involved in HIF-1
      complex activation by Ang II. More interestingly, this modulation of HIF-1 is at
      different degrees and through different pathways. Our results show that
      transactivation of IGF-I receptor is essential for HIF-1alpha protein translation
      through phosphatidylinositol 3-kinase/p70S6 kinase pathway activation, and
      epidermal growth factor receptor transactivation is implicated in HIF-1 complex
      activation through the stimulation of the p42/p44 MAPK pathway. Our results
      therefore show that Ang II-induced receptor tyrosine kinase transactivation is
      essential in both the induction and activation of HIF-1. These findings identify
      novel and intricate signaling mechanisms involved in HIF-1 complex activation.

PMID- 17510241
TI  - C-type natriuretic peptide forms in the ovine fetal and maternal circulations:
      evidence for independent regulation and reciprocal response to undernutrition.
AB  - C-type natriuretic peptide (CNP) has a crucial role in postnatal endochondral
      bone growth and is rapidly responsive to changes in nutrition. Although CNP is
      expressed in the placenta, little is known about the regulation and role of CNP
      in fetal-maternal health. We hypothesized that CNP may be similarly responsive to
      undernutrition in the growing fetus, in which maternal nutrition is crucial to
      normal growth and development. We therefore studied maternal and fetal CNP and
      the aminoterminal (bioinactive) fragment of proCNP (NTproCNP) in 39 chronically
      catheterized pregnant sheep before and after a 3-d maternal fast from 121 d
      gestation. Maternal CNP and NTproCNP levels were higher than in the fetus (CNP 12
      fold, NTproCNP 1.5-fold, both P < 0.001). The ratio of NTproCNP to CNP was higher
      in the fetus than the mother (53 +/- 3 vs. 8.7 +/- 0.6, P < 0.001), suggesting
      enhanced synthesis and/or degradation of CNP in the fetus. As in postnatal lambs,
      fetal plasma CNP forms fell promptly during maternal fasting. In contrast,
      maternal levels exhibited reciprocal and contemporaneous increase, which was
      reversed by refeeding. Uteroplacental production of CNP was suggested by a high
      venoarterial concentration gradient across the gravid uterus, and a correlation
      between maternal NTproCNP levels and placental weight (r(2) = 0.26, P = 0.01).
      These studies provide the first evidence that CNP is regulated independently in
      the fetus. Reciprocal increases in maternal CNP forms may reflect the response of
      the uteroplacental unit to substrate deficiency. CNP may have a role in
      maintaining fetal welfare and provides a possible marker of uteroplacental
      nutrient supply.

PMID- 17510242
TI  - The postimplantation embryo differentially regulates endometrial gene expression
      and decidualization.
AB  - Transcriptomal changes in the uterine endometrium induced in response to the
      implanting embryo remain largely unknown. In this study, using Affymetrix mRNA
      expression microarray analysis, we identified genes differentially expressed in
      the murine endometrium in the presence or absence of the embryo. Compared with
      the pseudopregnant deciduoma induced by a mechanical stimulus in the absence of
      an embryo, approximately 1500 genes (753 up-regulated, 686 down-regulated; P <
      0.05) were differentially expressed by at least 1.2-fold in the uterine decidua
      of pregnancy. Most of these genes fall into five major biological categories that
      include binding (45%), catalysis (24%), signal transduction (10%),
      transcriptional regulators (5%), and transporters (5%). This strong, embryo
      induced transcriptomal impact represented approximately 10% of the total number
      of genes expressed in the decidualizing endometrium. Validation studies with mRNA
      and protein confirmed existence of the phylogenetically conserved, embryo
      regulated genes involved in the following: 1) hemostasis and inflammation; 2)
      interferon signaling; 3) tissue growth and remodeling; and 4) natural killer cell
      function. Interestingly, whereas expression of many growth factors and their
      cognate receptors were not different between the decidual and deciduomal
      endometria, a number of proteases that degrade growth factors were selectively up
      regulated in the decidual tissue. Increased expression of IGF and activin A
      neutralizing factors (i.e. HtrA1 and Fstl3) correlated with reduced stromal cell
      mitosis, tissue growth, and mitogenic signaling in the decidual endometrium.
      These results support the hypothesis that the implanting murine embryo takes a
      proactive role in modulating endometrial gene expression and development during
      early gestation.

PMID- 17510243
TI  - Human chorionic gonadotropin (hCG) up-regulates wnt5b and wnt7b in the mammary
      gland, and hCGbeta transgenic female mice present with mammary Gland tumors
      exhibiting characteristics of the Wnt/beta-catenin pathway activation.
AB  - Transgenic (TG) mice expressing human chorionic gonadotropin (hCG) beta-subunit
      under the ubiquitin C promoter, presenting with a moderately elevated level of
      LH/hCG bioactivity develop multiple neoplasms secondary to the endocrine
      abnormalities, including mammary gland tumors after the age of 9 months. The
      increased levels of circulating estradiol, progesterone, and prolactin of the TG
      females after puberty boost the lobuloalveolar development in the mammary gland
      resulting ultimately in the formation of estrogen and progesterone receptor
      negative, malignant tumors. These tumors have a similar histopathology with those
      observed in TG mice with activated wnt/beta-catenin pathway, showing increased
      expression of beta-catenin, also a common finding in human breast tumors.
      Transdifferentiation is observed in mammary tumors of the hCGbeta TG mice,
      accompanied by abnormal expression of the Wnt genes in the tumorous and
      nontumorous mammary gland tissue. Specifically we found increased expression of
      Wnt5b in the TG mammary glands at the age of 3 months and up-regulation of Wnt7b
      and -5b in the subsequently appearing tumors. Importantly, hCG was found to up
      regulate these wnt ligands in mouse mammary gland, independent of the changes in
      ovarian steroidogenesis. Thus, the hCGbeta-overexpressing TG mice represent a
      novel model that links enhanced hCG action to dysregulated wnt signaling in the
      mammary gland, resulting in beta-catenin-stabilizing mammary tumorigenesis. The
      novel finding of hCG up-regulating wnt7b and wnt5b could contribute to pregnancy
      induced breast cancer in humans.

PMID- 17510245
TI  - Local actions of atrial natriuretic peptide counteract angiotensin II stimulated
      cardiac remodeling.
AB  - The cardiac hormones atrial and brain natriuretic peptides (NPs) counteract the
      systemic, hypertensive, and hypervolemic actions of angiotensin II (Ang II) via
      their guanylyl cyclase-A (GC-A) receptor. In the present study, we took advantage
      of genetically modified mice with conditional, cardiomyocyte (CM)-restricted
      disruption of GC-A (CM GC-A knockout mice) to study whether NPs can moderate not
      only the endocrine but also the cardiac actions of Ang II in vivo. Fluorometric
      measurements of [Ca(2+)](i) transients in isolated, electrically paced adult CMs
      showed that atrial NP inhibits the stimulatory effects of Ang II on free
      cytosolic Ca(2+) transients via GC-A. Remarkably, GC-A-deficient CMs exhibited
      greatly enhanced [Ca(2+)](i) responses to Ang II, which was partly related to
      increased activation of the Na(+)/H(+)-exchanger NHE-1. Chronic administration of
      Ang II to control and CM GC-A knockout mice (300 ng/kg body weight per minute via
      osmotic minipumps during 2 wk) provoked significant cardiac hypertrophy, which
      was markedly exacerbated in the later genotype. This was concomitant to increased
      cardiac expression of NHE-1 and enhanced activation of the Ca(2+)/calmodulin
      dependent prohypertrophic signal transducers Ca(2+)/calmodulin-dependent kinase
      II and calcineurin. On the basis of these results, we conclude that NPs exert
      direct local, GC-A-mediated myocardial effects to antagonize the [Ca(2+)](i)
      dependent hypertrophic growth response to Ang II.

PMID- 17510244
TI  - Follicle-stimulating hormone increases tuberin phosphorylation and mammalian
      target of rapamycin signaling through an extracellular signal-regulated kinase
      dependent pathway in rat granulosa cells.
AB  - FSH-mediated regulation of mammalian target of rapamycin (mTOR) signaling in
      proliferating granulosa cells and the effect of dihydrotestosterone (DHT) on this
      pathway were examined. Inhibiting mTOR activation using rapamycin significantly
      reduced the FSH-mediated increase in cyclin D2 mRNA expression, suggesting that
      mTOR plays a role in the FSH-mediated increase in granulosa cell proliferation.
      FSH treatment of granulosa cells showed a 2-fold increase in phosphorylation of
      p70S6 kinase (p70S6K), the downstream target of mTOR. The increase in p70S6K
      phosphorylation by FSH treatment was abolished by prior exposure to DHT,
      suggesting that DHT inhibits FSH-mediated activation of mTOR signaling in
      cultured granulosa cells. The effect of FSH and DHT treatment on tuberin (TSC2),
      the upstream regulator of mTOR, was then examined. FSH treatment increased TSC2
      phosphorylation, and pretreatment with DHT for 24 h reduced this stimulation.
      These results indicate that reduced p70S6K phosphorylation observed in DHT
      treated cells might be the result of reduced TSC2 phosphorylation. Because Akt is
      the upstream activator of TSC2 phosphorylation, the effect of Akt inhibition was
      examined to test whether FSH-mediated TSC2 phosphorylation proceeds through an
      Akt-dependent pathway. Our results show that inhibiting Akt phosphorylation did
      not block FSH-stimulated TSC2 phosphorylation, whereas ERK inhibition reduced FSH
      mediated stimulation. These results demonstrate the involvement of ERK rather
      than Akt in FSH-mediated TSC2 phosphorylation in granulosa cells. Based on these
      observations, we conclude that in granulosa cells, FSH uses a protein kinase A
      /ERK-dependent pathway to stimulate TSC2 phosphorylation and mTOR signaling, and
      DHT treatment significantly reduces this response.

PMID- 17510246
TI  - Gene expression from the imprinted Dio3 locus is associated with cell
      proliferation of cultured brown adipocytes.
AB  - Active thyroid hormones are critical for the differentiation and function of
      brown adipose tissue. However, we have observed high basal and induced levels of
      type 3 deiodinase (D3), an enzyme that inactivates thyroid hormones and is coded
      by the imprinted gene Dio3, in differentiating brown preadipocytes in primary
      culture. We find that D3 activity and mRNA expression strongly correlate with the
      rate of proliferation of undifferentiated precursor cells under various
      conditions. Furthermore, differentiation of precursor cells to adipocytes is
      associated with decreased levels of D3 expression, and only very low levels of D3
      mRNA are found in mature adipocytes. Dlk1, an inhibitor of adipocyte
      differentiation and a paternally expressed gene located in the same imprinted
      domain as Dio3, displayed changes in expression that parallel those of Dio3. In
      contrast, a 4-kb transcript for Dio3os, an antisense gene also located in the
      same imprinted domain, is markedly up-regulated in differentiated adipocytes. We
      conclude that D3 expression in differentiating preadipocytes is primarily linked
      to proliferating cells, whereas Dio3os expression is associated with mature
      adipocytes. Our results suggest that genomic imprinting and gene expression at
      the Dlk1/Dio3 imprinted domain may play a role in the regulation of adipocyte
      proliferation and differentiation.

PMID- 17510247
TI  - Liquid chromatography/tandem mass spectrometry detection of covalent binding of
      acetaminophen to human serum albumin.
AB  - Covalent binding of reactive electrophilic intermediates to proteins is
      considered to play an important role in the processes leading to adverse drug
      reactions and idiosyncratic drug reactions. Consequently, both for the discovery
      and the development of new drugs, there is a great interest in sensitive
      methodologies that enable the detection of covalent binding of drugs and drug
      candidates in vivo. In this work, we present a strategy for the generation and
      analysis of drug adducts to human serum albumin. Our methodology is based on the
      isolation of albumin from blood, its digestion to peptides by pronase E, and the
      sensitive detection of adducts to the characteristic cysteine-proline
      phenylalanine (CPF) tripeptide by liquid chromatography/tandem mass spectrometry.
      We chose acetaminophen (APAP) as a model compound because this drug is known to
      induce covalent binding to proteins when bioactivated by cytochromes P450 to its
      reactive N-acetyl-p-benzoquinoneimine metabolite. First, by microsomal
      incubations of APAP in presence of CPF and/or intact albumin, in vitro reference
      adducts were generated to determine the mass spectrometric characteristics of the
      expected CPF adducts and to confirm their formation on pronase E digestion of the
      alkylated protein. When applying this methodology to albumin isolated from blood
      of patients exposed to APAP, we were indeed able to detect the corresponding CPF
      adducts. Therefore, this strategy could be seen as a potential biomonitoring tool
      to detect in vivo reactive intermediates of drugs and drug candidates, e.g., in
      the preclinical and clinical development phase.

PMID- 17510248
TI  - Absorption, distribution, metabolism, and elimination of the direct renin
      inhibitor aliskiren in healthy volunteers.
AB  - Aliskiren (2(S),4(S),5(S),7(S)-N-(2-carbamoyl-2-methylpropyl)-5-amino-4-hydroxy
      2,7-diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy)phenyl]-octanamid hemifumarate)
      is the first in a new class of orally active, nonpeptide direct renin inhibitors
      developed for the treatment of hypertension. The absorption, distribution,
      metabolism, and excretion of [(14)C]aliskiren were investigated in four healthy
      male subjects after administration of a single 300-mg oral dose in an aqueous
      solution. Plasma radioactivity and aliskiren concentration measurements and
      complete urine and feces collections were made for 168 h postdose. Peak plasma
      levels of aliskiren (C(max)) were achieved between 2 and 5 h postdose. Unchanged
      aliskiren represented the principal circulating species in plasma, accounting for
      81% of total plasma radioactivity (AUC(0-infinity)), and indicating very low
      exposure to metabolites. Terminal half-lives for radioactivity and aliskiren in
      plasma were 49 h and 44 h, respectively. Dose recovery over 168 h was nearly
      complete (91.5% of dose); excretion occurred almost completely via the fecal
      route (90.9%), with only 0.6% recovered in the urine. Unabsorbed drug accounted
      for a large dose proportion recovered in feces in unchanged form. Based on
      results from this and from previous studies, the absorbed fraction of aliskiren
      can be estimated to approximately 5% of dose. The absorbed dose was partly
      eliminated unchanged via the hepatobiliary route. Oxidized metabolites in excreta
      accounted for at least 1.3% of the radioactive dose. The major metabolic pathways
      for aliskiren were O-demethylation at the phenyl-propoxy side chain or 3-methoxy
      propoxy group, with further oxidation to the carboxylic acid derivative.

PMID- 17510249
TI  - The radiology task: Bayesian theory and perception.
AB  - The use of a Bayesian framework to understand how radiologists search images for
      pathology is important as it formalizes, mathematically, how visual and cognitive
      processes control eye movements by modelling the ideal searcher against which
      human performance can be compared. It is important that the interpretation of
      medical images is understood so that new developments in the ways images are
      presented and the use of image processing software are matched to human abilities
      and limitations.

PMID- 17510250
TI  - Improved focal liver lesion detection: comparison of single-shot diffusion
      weighted echoplanar and single-shot T2 weighted turbo spin echo techniques.
AB  - The purpose of this study was to compare diffusion-weighted respiratory-triggered
      single-shot spin echo echoplanar imaging (SS SE-EPI) sequence using four b-values
      (b = 0, b = 20, b = 300, b = 800 s mm(-2)) and single-shot T2 weighted turbo spin
      echo (T2W SS TSE) in patients with focal liver lesions, with special interest in
      small (<10 mm) lesions. Twenty-four patients underwent routine MRI. The five
      sequences were compared qualitatively for image quality, lesion conspicuity and
      artefacts. Quantitative analysis was performed for lesion identification and
      lesion-to-liver contrast-to-noise ratio (CNR). Subgroup analyses were performed
      for different types of lesions with different sizes. Sequences were compared by
      rank order statistic (RIDIT) and Kruskal-Wallis test. The best image quality
      (p<0.05) was achieved with T2W TSE and the best lesion conspicuity (p<0.05) with
      T2W TSE for biliary cysts and SE-EPI diffusion-weighted imaging (DWI) (b = 20 s
      mm(-2)) for haemangiomas and metastases. Image artefacts were lowest (p<0.05)
      with T2W TSE. T2W TSE was found to be the best protocol (p<0.05) for the
      identification of biliary cysts and SE-EPI DWI (b = 20 s mm(-2)) for haemangiomas
      and metastases. The lesion-to-liver CNRs were highest on T2W TSE for biliary
      cysts and on SE-EPI diffusion-weighted imaging (DWI) for haemangiomas and
      metastases (p<0.05). This study shows the potential of SS SE-EPI DWI (especially
      with a b-value of 20 s mm(-2)) as a promising technique for detecting small (<10
      mm) focal liver lesions.

PMID- 17510251
TI  - High-density mapping at pulmonary veins antrum: a new tool for atrial
      fibrillation ablation.

PMID- 17510252
TI  - Regression of mitral regurgitation after cardiac resynchronization therapy in an
      adult with preserved left ventricular function and right ventricular pacing.
AB  - We report the case of a 60-year-old patient with preserved ventricular function
      and no organic mitral leaflet disease implanted with a dual-chamber pacemaker.
      Right ventricular pacing induced a major ventricular dyssynchrony, a severe
      mitral regurgitation, and symptoms of congestive heart failure. Upgrading to a
      biventricular device was associated with a decrease in the symptoms, the
      ventricular dyssynchrony, and the mitral regurgitation.

PMID- 17510253
TI  - CodY-affected transcriptional gene expression of Streptococcus pyogenes during
      growth in human blood.
AB  - In an attempt to expand the available knowledge of pathogen-host interactions
      during ex vivo growth of Streptococcus pyogenes (GAS) in nonimmune whole human
      blood, the extents to which the expression of 51 genes including regulators with
      known targets, established virulence factors, physiologically important
      transporters and metabolic enzyme genes was differentially affected in the
      presence or absence of a functional codY gene were determined. The results
      obtained by quantitative real-time PCR using the M49 strain NZ131 showed that
      CodY influenced GAS gene activity in a dynamic fashion, with differential
      responses detected for 26 genes and occasionally characterized by discordance in
      the blood environment compared to laboratory medium. Degenerate derivatives of
      the recently discovered CodY box potentially serving as a cis-regulatory element
      for CodY action were identified in the upstream regions of 15 genes of the NZ131
      genome, and these genes featured sequence motifs identical to the NZ131 CodY box
      in all completely sequenced S. pyogenes genomes. As none of these genes
      represented a genuine virulence factor, it seems likely, therefore, that the
      observed differential transcription of the majority of virulence genes was caused
      by indirect actions of CodY as part of a regulatory network.

PMID- 17510254
TI  - Molecular characterization and analysis of a gene encoding the acidic repeat
      protein (Arp) of Treponema pallidum.
AB  - The acidic repeat protein (arp) genes from three subspecies of the treponeme
      Treponema pallidum (T. pallidum subsp. pallidum, Nichols strain; T. pallidum
      subsp. pertenue, CDC-1 and CDC-2 strains; and T. pallidum subsp. endemicum,
      Bosnia A strain) were cloned and sequenced. The predicted protein sequence
      contained a high percentage of glutamic acid, hence the name acidic repeat
      protein, or Arp. The protein had a potential membrane-spanning domain and a
      signal peptidase I site. The gene from the Nichols strain of T. pallidum subsp.
      pallidum contained a set of 14 nearly identical repeats of a 60 bp sequence,
      which occupied approximately 51 % of the length of the gene. Analyses of arp from
      laboratory strains showed that the 5' and 3' ends of the genes were conserved,
      but there was considerable heterogeneity in the number of repeats of this 60 bp
      sequence. Based on amino acid variations, the 14 sequence repeats could be
      classified into three types, which were named type I, type II and type III
      repeats. The type II repeat was the most common in the strains examined. The arp
      gene of the Nichols strain was subsequently cloned into the expression vector
      pBAD/TOPO ThioFusion. The expressed protein was detected in a Western blot assay
      using rabbit immune sera produced against T. pallidum, or synthetic peptides
      derived from the repeat sequences. Using an ELISA, rapid plasma reagin (RPR) test
      positive sera reacted with synthetic peptides derived from the repeat region but
      not with peptides derived from N and C termini of the Arp protein. These results
      show that the Arp protein is immunogenic and could prove to be a useful target
      for serological diagnosis of T. pallidum infection.

PMID- 17510255
TI  - Comparison of virulence-associated in vitro properties of typed strains of
      Campylobacter jejuni from different sources.
AB  - Campylobacter jejuni is a major cause of human diarrhoeal disease, but specific
      virulence mechanisms have not been well defined. This blinded study was
      undertaken with 40 C. jejuni isolates from different sources to determine their
      haemolytic, cytotoxic and adhesion and invasion activities towards mammalian
      cells. The results were correlated with source of isolation and genetic makeup by
      amplified fragment length polymorphism (AFLP) typing. The isolates had variable
      degrees of haemolytic activity against rabbit erythrocytes and cytotoxicity
      towards CaCo-2, HeLa and Vero cells. The data indicated that the haemolytic and
      cytotoxic activities were due to separate factors. A range of cytotoxicity was
      exhibited, whereby some strains had no activity against the target cells and
      others had activity against all three cell lines. Certain strains had activity
      against CaCo-2 cells but little or no activity against the other cells, while
      others exhibited the opposite phenotype. The data suggested that the cytotoxicity
      assay with the different cell lines may have detected more than one cytotoxin. A
      wide variation between isolates was observed for both adherence and invasion with
      all three cell lines, yet, overall, the strains showed a significantly greater
      invasion capacity for CaCo-2. There was no clear relationship between source of
      isolation or disease manifestation and possession of statistically significantly
      higher levels of particular virulence-associated factors although, in some cases,
      a correlation between cytotoxicity and cell invasion was evident. Five AFLP
      clusters, each representing two to eleven isolates with similar profiles, were
      observed at the 90 % similarity level. Some AFLP groups contained isolates with a
      common serotype, but each group had C. jejuni isolates from more than one source
      with the exception of group IV, which contained only human isolates. Isolates
      with high cytotoxic activity against CaCo-2 cells were confined to groups I, III
      and IV and a group of unrelated strains (U). Group II isolates had uniformly low
      cytotoxicity. Isolates in groups I, V and U were more invasive for CaCo-2 cells
      than isolates in groups II, III and IV. The strain differences in cytotoxicity or
      invasion did not correlate with source of isolation.

PMID- 17510256
TI  - Use of a colorimetric assay to measure differences in cytotoxicity of
      Mycobacterium tuberculosis strains.
AB  - Several techniques have been used to quantify the cytotoxicity produced by
      Mycobacterium tuberculosis bacilli on cell monolayers; however, they are semi
      quantitative or time consuming. Herein, a method based on crystal violet (CV)
      uptake by THP-1 cell monolayers is described. This colorimetric method quantifies
      the cytotoxic effect as a function of the number of remaining cells after the
      infection with M. tuberculosis. Since this micro-organism is not stained by the
      dye, it does not produce a background that affects absorbance readings. As
      determined by CV assay (CVA), M. tuberculosis strain H37Rv destroyed 10.5 % of
      THP-1 cell monolayers at 24 h and 50.52 % at 72 h, while M. tuberculosis strains
      lacking the complete phospholipase C locus produced a reduced cytotoxic effect.
      The damage estimated by microscopy corresponded to the effect quantified by CVA.
      The results show that the use of CVA is a rapid, sensitive and reliable
      quantitative assay to measure the cytotoxicity of different M. tuberculosis
      strains.

PMID- 17510257
TI  - Diversity of biofilms produced by quorum-sensing-deficient clinical isolates of
      Pseudomonas aeruginosa.
AB  - The quorum-sensing (QS) systems control several virulence attributes of
      Pseudomonas aeruginosa. Five QS-deficient P. aeruginosa clinical isolates (CI)
      that were obtained from wound (CI-1), tracheal (CI-2, CI-3, CI-4) and urinary
      tract (CI-5) infections had previously been characterized. In this study, a flow
      through continuous-culture system was utilized to examine in detail the biofilms
      formed by these isolates in comparison with the P. aeruginosa prototrophic strain
      PAO1. Analysis of the biofilms by confocal laser scanning microscopy and COMSTAT
      image analysis at 1 and 7 days post-inoculation showed that the isolates produced
      diverse biofilms. In comparison with PAO1, the CI produced biofilms that scarcely
      or partially covered the surface at day 1, although CI-1 produced larger
      microcolonies. At day 7, CI-2 and CI-4 produced mature biofilms denser than that
      produced by PAO1, while the biofilm formed by CI-1 changed very little from day
      1. CI-1 was defective in both swarming and twitching motilities, and
      immunoblotting analysis confirmed that it produced a reduced level of PilA
      protein. The twitching-motility defect of CI-1 was not complemented by a plasmid
      carrying intact pilA. In the 48 h colony biofilm assay, the CI varied in
      susceptibility to imipenem, gentamicin and piperacillin/tazobactam. These results
      suggest that: (1) the isolates produced biofilms with different structures and
      densities from that of PAO1; (2) biofilm formation by the isolates was not
      influenced by either the isolation site or the QS deficiencies of the isolates;
      (3) the behaviour of CI-1 in the different biofilm systems may be due to its lack
      of swarming motility and type IV pilus-related twitching motility.

PMID- 17510259
TI  - Rapid characterization of the normal and disturbed vaginal microbiota by
      application of 16S rRNA gene terminal RFLP fingerprinting.
AB  - Bacterial vaginosis (BV) is a prevalent infection in women of reproductive age
      associated with numerous sequelae, including preterm delivery, amniotic fluid
      infections and an increased risk of acquiring sexually transmitted diseases. The
      vaginal microbiota in BV patients is characterized by a shift from lactobacilli
      to a diverse spectrum of mostly anaerobic bacteria. In this study, terminal
      restriction fragment length polymorphism (T-RFLP) was used to characterize the
      vaginal bacterial communities from 50 women with BV and 20 healthy subjects. In
      the BV samples, 23 species or phylotypes from 17 genera could be identified,
      including Atopobium vaginae, Megasphaera sp., Lactobacillus iners, Gardnerella
      vaginalis and three recently described phylotypes from the order Clostridiales.
      The number of detected species or phylotypes was on average 6.3 per sample (range
      2-14). In contrast, in normal samples, only Lactobacillus species could be
      identified. In conclusion, T-RFLP provides a rapid and reliable technique to
      investigate the diversity of the predominant vaginal microbiota and allows
      differentiation of the flora of BV and healthy women. As such, T-RFLP may be
      helpful both in the diagnosis of BV from vaginal fluids and in a better
      understanding of the bacterial succession involved in the aetiology of BV.

PMID- 17510258
TI  - Identification of a group of shigella-like isolates as Shigella boydii 20.
AB  - Infections by Shigella species are an important cause of diarrhoeal disease
      worldwide. Of 4198 Shigella isolates received by the French National Reference
      Centre for Escherichia coli and Shigella, 180 from patients with diarrhoea and
      dysentery in 2000-2004 did not react with any available polyclonal rabbit
      antisera used to identify the established Shigella serogroups. This study
      describes the molecular and phenotypic characteristics of these isolates in
      seroagglutination tests, molecular serotyping (rfb-RFLP and fliC-RFLP),
      ribotyping, detection of invasivity and enterotoxins genes, and antibiotic
      sensitivity. All isolates gave biochemical reactions typical of Shigella boydii,
      were mannitol-positive and indole-negative. They all carried invasion-associated
      genes, enterotoxin 2 [ShET-2] and an IS630 sequence. They had a unique ribotype
      that was distinct from all other Shigella and E. coli patterns. Further
      characterization by rfb-RFLP clearly distinguished this serogroup from all other
      Shigella or E. coli O-groups. The fliC-RFLP pattern corresponded to P4, an F
      pattern which is associated with 10 different serogroups of S. boydii. A new
      antiserum prepared against strain 00-977 agglutinated all 180 isolates and cross
      agglutination and absorption studies with anti-00-977 serum and anti-CDC 99-4528
      (reference for the newly described S. boydii serogroup 20) serum showed identical
      antigenic structure. Furthermore, strains 00-977 and CDC 99-4528 had the same
      molecular serotype, ribotype and virulence genes.

PMID- 17510260
TI  - Evaluation of Albicans ID2 and Biggy agar for the isolation and direct
      identification of vaginal yeast isolates.
AB  - In this study, 250 vaginal samples from patients with vulvovaginal candidosis
      were inoculated onto two chromogenic media, Albicans ID(2) and Biggy agar, as
      well as onto Sabouraud chloramphenicol agar, yielding a total of 63 yeast (25.2
      %) on all three media. These strains were identified as Candida glabrata in 20
      (31.8 %) samples, Candida albicans in 15 samples (23.8 %), Candida tropicalis in
      10 samples (15.9 %), Candida krusei in five samples (7.9 %), Candida kefyr in
      five samples (7.9 %), Candida dubliniensis in four samples (6.3 %), Candida
      parapsilosis in two samples (3.2 %) and Candida guilliermondii in two samples
      (3.2 %). Mixed fungal cultures and bacterial growth or filamentous fungi were not
      detected on any of the selected media. The sensitivity and specificity of the
      Albicans ID(2) and Biggy agar with regard to the identification of C. albicans
      were 80.0 and 64.6 %, and 86.7 and 56.3 %, respectively. This study showed these
      two chromogenic media to be as effective as Sabouraud chloramphenicol agar with
      respect to fungal detection. However, neither Albicans ID(2) nor Biggy agar was
      sufficient for reliable differentiation of yeasts to the species level.

PMID- 17510261
TI  - Rapid quantification of hepatitis B virus DNA by direct real-time PCR from serum
      without DNA extraction.
AB  - The purpose of this study was to quantify hepatitis B virus DNA by direct real
      time PCR from serum without the need for DNA extraction. Crossing point (Cp)
      values were determined automatically using the second derivative maximum mode.
      Since serum samples from patients are inevitably haemolysed, lipaemic or icteric,
      the interference of endogenous substances from the serum in real-time PCR was
      evaluated. The result showed that, although serum protein quenched the intensity
      of fluorescence, the Cp value adopted to calculate the quantity of DNA copies
      remained unchanged. Importantly, real-time PCR from serum with or without DNA
      extraction reached a high level of concordance. This direct serum PCR method
      without the DNA extraction and gel electrophoresis allows for substantial labour
      and cost savings. In addition, it is also suitable for rapid DNA quantification
      during clinical diagnosis.

PMID- 17510262
TI  - Real-time PCRs for detection of Trichomonas vaginalis beta-tubulin and 18S rRNA
      genes in female genital specimens.
AB  - Trichomonas vaginalis is the cause of one of the most common types of vaginitis,
      trichomoniasis. The incidence of trichomoniasis in developed countries has
      decreased substantially during the past decade, but high prevalence of this
      disease can still be found in rural and remote areas of Australia. Clinical
      manifestations of symptomatic women are generally non-specific, but include
      vaginal discharge, vaginitis and irritation. T. vaginalis infection has also been
      linked to the increased risk of human immunodeficiency virus transmission.
      Current diagnosis of T. vaginalis relies on the visualization of motile organisms
      in a wet-mount preparation. Culture is used mainly in reference laboratories. The
      latter two methods require viable organisms and would not be suitable for use
      where transportation of specimens can be delayed. Two real-time fluorescence
      resonance energy transfer (FRET) hybridization probe PCR assays were used in this
      study to test for T. vaginalis DNA, targeting the beta-tubulin and 18S rRNA
      genes. We tested 500 randomly selected female patients, in an STD setting, for T.
      vaginalis DNA. The FRET PCRs targeting the beta-tubulin gene and the 18S rRNA
      gene detected 96 % (85/89) and 100 % (89/89) , respectively, of the positive
      specimens (first-void urine sample or genital swabs). Wet-mount microscopy was
      performed on 76 of these PCR-positive specimens and showed a sensitivity of 38 %
      (29/76). The prevalence, by PCR, of trichomoniasis was 18 % in this study. The
      two real-time PCRs developed in this study, targeting different genetic regions
      of the organism, provide a rapid, sensitive and specific diagnosis of T.
      vaginalis infection.

PMID- 17510263
TI  - Species identification and strain differentiation of clinical Candida isolates
      using the DiversiLab system of automated repetitive sequence-based PCR.
AB  - The DiversiLab system, which uses repetitive sequence-based PCR (rep-PCR) to
      genotype micro-organisms, was evaluated as a molecular typing tool for members of
      the genus Candida. Initially, 41 clinical Candida spp. (7 Candida krusei, 10
      Candida parapsilosis, 7 Candida albicans, 10 Candida tropicalis and 7 Candida
      glabrata), previously identified at the species level by morphological and
      biochemical analysis, were analysed with the DiversiLab system. Species
      identification was confirmed by DNA sequence analysis of the contiguous internal
      transcribed spacer (ITS) region (ITS1-5.8S-ITS2). On the basis of an 80 %
      similarity threshold, rep-PCR consistently clustered like species and this set of
      isolates, along with five ATCC reference strains, was used to create a DNA
      fingerprint library with the DiversiLab software. Subsequently, an additional set
      of 115 clinical Candida isolates, identified biochemically as C. albicans (n=94),
      C. glabrata (n=8), C. parapsilosis (n=5), C. tropicalis (n=3), C. krusei (n=3)
      and Candida lusitaniae (n=2), isolated at a regional reference laboratory, were
      typed using DiversiLab. One hundred and six of these isolates clustered with
      members of the Candida library at >80 % similarity and thus could be assigned
      species identification, and initial calculations showed that identification via
      rep-PCR fingerprinting was 95 % concordant (101/106) with the
      biochemical/morphological identification. However, ITS region sequencing of the
      five discrepant samples, as well as the nine isolates that were <80 % similar to
      the database samples, showed that nine were misidentified with traditional
      biochemical/morphological methods. For the misidentified isolates, the sequence
      based identification was in agreement with the DiversiLab clustering, yielding an
      actual correlation of >99 %. As traditional techniques can take several days to
      provide information about Candida at the genus/species level, genotyping with the
      DiversiLab system holds promise for more-rapid speciation of members of this
      genus. This system may also be useful for epidemiological studies such as source
      tracking that require Candida subspecies discrimination.

PMID- 17510265
TI  - In vitro activity of piperacillin/tazobactam and ertapenem against Bacteroides
      fragilis and Escherichia coli in pure and mixed cultures.
AB  - Ertapenem and piperacillin/tazobactam are beta-lactam antibiotics with a broad
      spectrum of activity used for the treatment of mixed infections in which
      Bacteroides fragilis and Escherichia coli play an important aetiological role. In
      this study, the activities of piperacillin/tazobactam and ertapenem (MIC and time
      kill kinetics) against these bacteria were compared. MICs were determined by the
      agar dilution method, and the time and slope of time-kill curves were analysed.
      In the in vitro pharmacodynamic assays, pure and mixed cultures of E. coli and B.
      fragilis were exposed to peak concentrations of ertapenem (8.0 microg ml(-1)) and
      piperacillin/tazobactam (64.0/8.0 microg ml(-1)) for 48 h. Treatment with
      ertapenem reduced the viability of E. coli and/or B. fragilis by 3 logs in all
      experiments, whereas piperacillin/tazobactam only affected the viability of B.
      fragilis. Both drugs exhibited their fastest rates of killing when bacteria were
      grown in mixed cultures. According to the results, ertapenem exhibited activity
      similar to that of piperacillin/tazobactam against B. fragilis alone or in mixed
      culture. However, ertapenem exhibited a markedly higher activity against E. coli
      alone or in combination with B. fragilis relative to piperacillin/tazobactam.

PMID- 17510267
TI  - Role of AmpD, OprF and penicillin-binding proteins in beta-lactam resistance in
      clinical isolates of Pseudomonas aeruginosa.
AB  - In this study, the mechanisms leading to increased chromosomal AmpC beta
      lactamase expression and the contributory roles of the outer-membrane protein
      OprF and penicillin-binding proteins were analysed in 33 characterized clinical
      isolates of Pseudomonas aeruginosa. The genes ampD and ampE were analysed by PCR
      and DNA sequencing. Expression of the gene oprF was assessed using real-time RT
      PCR, and penicillin-binding proteins were analysed using a chemiluminescence
      assay. Several of the isolates with increased ampC expression had major deletions
      affecting ampD, although in some isolates the mechanism of increased ampC
      expression could not be ascertained. Occasional isolates had increased expression
      of both ampC and oprF but remained susceptible to cephalosporins, suggesting that
      increased beta-lactamase activity could not offset increased outer-membrane
      permeability. There were no discernible changes in penicillin-binding proteins.
      Genomic deletions in ampD were observed in selected clinical isolates of P.
      aeruginosa with increased expression of the AmpC beta-lactamase. For some
      isolates, cephalosporin resistance was dependent upon the interplay of ampC and
      oprF expression.

PMID- 17510266
TI  - Two diallyl sulphides derived from garlic inhibit meticillin-resistant
      Staphylococcus aureus infection in diabetic mice.
AB  - The inhibitory effect of diallyl sulphide (DAS) and diallyl disulphide (DADS)
      against meticillin-resistant Staphylococcus aureus (MRSA) infection in diabetic
      mice was studied. The influence of these agents on the plasma levels of
      fibronectin, C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour
      necrosis factor-alpha (TNF-alpha), and on the activity of plasminogen activator
      inhibitor-1 (PAI-1), antithrombin III (AT-III) and protein C, in MRSA-infected
      diabetic mice was examined. To induce diabetes, mice were treated
      intraperitoneally with streptozotocin for 5 consecutive days. Ten clinical MRSA
      isolates obtained from infected patients were used in this study. Diabetic mice
      were infected by injecting 200 microl MRSA/PBS suspension containing 10(7) c.f.u.
      via the tail vein. At day 4 post-infection, 200 microl DAS or DADS was
      administrated twice orally with an interval of 12 h. Eight hours after each
      administration, the blood and organs of mice were collected. Results showed that
      DAS and DADS significantly decreased MRSA viability in the kidney (P<0.05), with
      administration of each agent twice showing a greater inhibitory effect than when
      given once (P<0.05). MRSA infection in diabetic mice significantly elevated the
      plasma levels of IL-6 and TNF-alpha (P<0.05). DAS or DADS given once did not
      affect the plasma levels of IL-6 and TNF-alpha (P>0.05); however, DAS or DADS
      given twice significantly decreased the plasma levels of both IL-6 and TNF-alpha
      (P<0.05). DAS and DADS treatments also significantly reduced the plasma levels of
      CRP, fibronectin and fibrinogen (P<0.05). DAS or DADS treatment did not affect
      PAI-1 activity (P>0.05), but DAS or DADS given twice significantly increased AT
      III activity (P<0.05). DADS given twice elevated protein C activity (P<0.05).
      MRSA infection significantly increased malondialdehyde levels in the kidney and
      spleen (P<0.05), and these levels were significantly decreased by treatment with
      DAS or DADS (P<0.05). These data suggest that DAS and DADS could provide multiple
      protective functions against MRSA infection in diabetic mice.

PMID- 17510264
TI  - Typing of Histoplasma capsulatum strains by fatty acid profile analysis.
AB  - The performance of fatty acid profiling for strain differentiation of Histoplasma
      capsulatum was assessed. Total fatty acids were isolated from the yeast-phase
      cells of seven stock and two previously unreported clinical strains of H.
      capsulatum var. capsulatum, as well as from one unreported clinical strain and
      one stock strain of H. capsulatum var. duboisii, and one strain of each of three
      other dimorphic zoopathogenic fungal species, Blastomyces dermatitidis,
      Paracoccidioides brasiliensis and Sporothrix schenckii. Different colony
      morphology and pigmentation types of the H. capsulatum strains were also
      included. The most frequently occurring fatty acids were oleic, palmitic, stearic
      and linoleic acids. There were variations in the relative percentage fatty acid
      contents of H. capsulatum strains that could be used for strain identification
      and discrimination. Differentiation between H. capsulatum strains was achieved by
      the comparison of detected fatty acids accompanied by principal component
      analysis using calculated Varimax-rotated principal component loadings.
      Statistical analysis yielded three major principal components that explained over
      94 % of total variance in the data. All the strains of H. capsulatum var.
      capsulatum RFLP classes II and III were grouped into two distinct clusters: the
      heterogenic RFLP class I formed a large, but also well-defined group, whereas the
      outgroup strains of H. capsulatum var. duboisii, B. dermatitidis, P. brasiliensis
      and S. schenckii were shifted away. These data suggest that fatty acid profiling
      can be used in H. capsulatum strain classification and epidemiological studies
      that require strain differentiation at the intraspecies level.

PMID- 17510268
TI  - Post-antifungal effects of the antifungal compound 2-(3,4-dimethyl-2,5-dihydro-1H
      pyrrol-2-yl)-1-methylethyl pentanoate on Aspergillus fumigatus.
AB  - The post-antifungal effect (PAFE) of the antifungal compound 2-(3,4-dimethyl-2,5
      dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate (DHP) upon Aspergillus fumigatus
      was investigated. The conidia of A. fumigatus were exposed to DHP at
      concentrations of 1 x and 4 x MIC(90) for variable times at 37 degrees C.
      Amphotericin B (AmB)-treated or drug-free controls were included in the study.
      DHP as well as AmB exposure resulted in prolonged lag phases of the turbidimetric
      growth curves. Both the treatments gave rise to delayed growth, with lag phases
      of 11 h upon treatment with a concentration of 4 x MIC(90) for 4 h. Furthermore,
      it was observed that DHP inhibited the expression of three A. fumigatus secretory
      proteins of 18, 42 and 55 kDa. One protein of 42 kDa was found to be a
      metalloprotease, which is an important virulence factor. Analysis of time
      dependent antigenic profiles showed the early expression of high-molecular-mass
      antigens. Expression of low-molecular-mass antigens started after 24 h culture.
      The antigens of A. fumigatus that are expressed during the early phase of growth
      were observed to be adversely affected after treatment with DHP. Although the
      mechanism of action of DHP to inhibit these proteins/antigens is unknown, the
      observations may be valuable to understand their role in the virulence of the
      pathogen, as well as the antigen-mediated responses caused by A. fumigatus.

PMID- 17510269
TI  - Pneumococci responsible for invasive disease and discharging ears in children in
      Sydney, Australia.
AB  - The serotypes and molecular clones of penicillin-nonsusceptible Streptococcus
      pneumoniae (PNSP) responsible for invasive pneumococcal disease (IPD) and
      discharging ears in metropolitan New South Wales were characterized to form a
      baseline prior to introduction of the heptavalent conjugate pneumococcal vaccine
      in Australia. Pneumococci isolated between 1 July 2000 and 30 June 2003 in Sydney
      from children <15 years were tested for antibiotic susceptibilities and
      serotyped. Penicillin-nonsusceptible pneumococci were typed by multilocus
      sequence typing and BOX PCR. During this period, 97 (13.9 %) of 698 pneumococci
      from IPD that were serotyped were penicillin-nonsusceptible. Of 607 pneumococci
      from discharging ears, 157 (26.1 %) were penicillin-nonsusceptible. Serotype 14
      was the predominant serotype responsible for IPD and serotype 19F predominated
      from discharging ears. The heptavalent vaccine serotypes accounted for 613 (87.8
      %) of all invasive isolates and 420 (69.8 %) of all isolates from discharging
      ears. Representatives of the major international clones were present among the
      PNSP. The majority of serotypes and clones that showed penicillin
      nonsusceptibility are present within the vaccine. Serotype switching was also
      noted to have occurred prior to introduction of the vaccine. This study provides
      a characterization of the pneumococcal serotypes associated with IPD and
      discharging ears that will be useful for detecting potential selective effects of
      the vaccine. This surveillance should be continued, as it will be important to
      monitor the frequency and distribution of serotypes in the post-vaccine era.

PMID- 17510270
TI  - Phenotypic and genotypic traits and epidemiological implication of Vibrio
      cholerae O1 and O139 strains in India during 2003.
AB  - During 2003, Vibrio cholerae O1 Ogawa was the predominant serotype among
      diarrhoeal patients admitted to different hospitals in India. With the exception
      of 3 strains from Kolkata, none of 172 strains examined exhibited resistance to
      tetracycline, but 45.7 % showed reduced susceptibility to ciprofloxacin.
      Extensive molecular characterization using randomly amplified polymorphic DNA
      analysis, ribotyping and PFGE revealed that almost all the strains within a
      serogroup were clonally related. Along with the H pulsotype, a newly described L
      pulsotype of recently emerged O1 Inaba strains was detected among the O1 Ogawa
      strains from 2003. The striking similarity in their molecular properties and
      antibiograms indicated that at least certain clones of recently emerged Inaba
      strains from 2004 may have evolved from O1 Ogawa strains. This view was further
      supported by the detection of a nearly identical wbeT region among the O1 Ogawa
      and recently emerged Inaba strains, the latter differing only by a single point
      mutation. Since 2003, a hiatus in the isolation of serogroup O139 was observed
      and these strains share the same PFGE profiles as those isolated during 2000.
      Organization of tandemly arranged CTX(El), CTX(Cal) and truncated CTX(Cal)
      (devoid of ctxAB) prophages was unique among the majority of these O139 strains.

PMID- 17510271
TI  - Role of the plasmid-encoded tet(O) gene in tetracycline-resistant clinical
      isolates of Campylobacter jejuni and Campylobacter coli.
AB  - The prevalence of tetracycline resistance, tetracycline MICs and tet(O) gene
      localization were investigated in 83 Campylobacter isolates from patients
      suffering from acute gastroenteritis in Germany. Combined biochemical and
      molecular markers identified 74 isolates (89 %) as Campylobacter jejuni,
      including seven atypical isolates that failed to hydrolyse hippurate, and nine
      isolates (11 %) as Campylobacter coli. Tetracycline resistance was detected in
      six out of nine Campylobacter coli isolates (67 %) and 13 out of 74 C. jejuni
      isolates (18 %). Low-level tetracycline resistance was observed for C. coli (MIC
      16 microg ml(-1) for all strains), whereas C. jejuni showed high-level resistance
      (MIC >256 microg ml(-1) for all strains). Both low- and high-level tetracycline
      resistance was associated with the presence of the tet(O) gene. In C. jejuni,
      tet(O) was plasmid-encoded in 54 % of tetracycline-resistant isolates, whereas in
      C. coli, tet(O) appeared to be located on the chromosome.

PMID- 17510272
TI  - Diversity of antibiotic resistance integrative and conjugative elements among
      haemophili.
AB  - The objective of this study was to investigate the sequence diversity in a single
      country of a family of integrative and conjugative elements (ICEs) that are
      vectors of antibiotic resistance in Haemophilus influenzae and Haemophilus
      parainfluenzae, and test the hypothesis that they emerged from a single lineage.
      Sixty subjects aged 9 months - 13 years were recruited and oropharyngeal samples
      cultured. Up to 10 morphologically distinct Pasteurellaceae spp. were purified,
      and then the species were determined and differentiated by partial sequence
      analysis of 16S rDNA and mdh, respectively. ICEs were detected by PCR directed at
      five genes distributed evenly across the ICE. These amplicons were sequenced and
      aligned by the neighbour-joining algorithm. A total of 339 distinguishable
      isolates were cultured. ICEs with all 5 genes present were found in 9 of 110 (8
      %) H. influenzae and 21 of 211 (10 %) H. parainfluenzae, respectively. ICEs were
      not detected among the other Pasteurellaceae. A total of 20 of 60 (33 %) children
      carried at least 1 oropharyngeal isolate with an ICE possessing all 5 genes. One
      of the five genes, integrase, however, consisted of two lineages, one of which
      was highly associated with H. influenzae. The topology of neighbour-joining trees
      of the remaining four ICE genes was compared and showed a lack of congruence;
      though, the genes form a common pool among H. influenzae and H. parainfluenzae.
      This family of antibiotic resistance ICEs was prevalent among the children
      studied, was genetically diverse, formed a large gene pool, transferred between
      H. influenzae and H. parainfluenzae, lacked population structure and possessed
      features suggestive of panmixia, all indicating it has not recently emerged from
      a single source.

PMID- 17510273
TI  - Effects of vaccination by a recombinant antigen ureB138 (a segment of the beta
      subunit of urease) against Helicobacter pylori infection.
AB  - Helicobacter pylori has to counteract acidity during colonization in the stomach.
      The most important region for the enzymic activity of H. pylori urease,
      consisting of 138 aa (ureB138), was determined by a comparison of the homology of
      amino acid sequences, and a structural analysis, between urease of H. pylori and
      various other species. This region was expressed in Escherichia coli as a fusion
      protein with glutathione S-transferase (GST), which was cleaved by PreScission
      protease between the GST moiety and ureB138. The ureB138 protein was then
      purified by gel filtration. The polyclonal antibody (pAb) induced by immunization
      with the purified ureB138 could suppress urease activity by about 50 %, while the
      pAb against the H. pylori urease did not show any inhibitory effect at all.
      Immunohistochemical analysis indicated that the ureB138-specific pAb specifically
      recognized the H. pylori infecting human gastric tissues. The effects of
      vaccination of recombinant ureB138 against infection by this organism were also
      examined. Specific IgG and IgA antibodies against H. pylori urease were induced
      in the serum of mice immunized with ureB138. A reduction in the number of
      colonizing H. pylori was observed in mice treated with ureB138 compared to ones
      treated with BSA and infection control mice. In the protected mice, severe
      gastritis characterized by marked infiltration of mononuclear cells was noted
      compared with the gastritis observed in unprotected mice. Immunohistochemical
      staining for IgA in gastric mucosa showed that the number of mice positively
      stained with IgA was significantly higher in ureB138-vaccinated mice than in non
      vaccinated mice. This indicates that local IgA antibody and severe post
      immunization gastritis correlate well with the protection of mice against H.
      pylori infection.

PMID- 17510274
TI  - Molecular analysis of the NSP4 and VP6 genes of rotavirus strains recovered from
      hospitalized children in Rio de Janeiro, Brazil.
AB  - Group A rotaviruses are the main cause of acute gastroenteritis in children
      throughout the world. The two outer capsid proteins, VP4 and VP7, define the P
      and G genotypes, respectively. Rotaviruses with P[8]G1, P[4]G2, P[8]G3 and P[8]G4
      genotypes are predominant in infecting humans and the G9 genotype is emerging in
      most continents as the fifth most common G type worldwide. The inner capsid
      protein VP6 is responsible for subgroup (SG) specificities, allowing
      classification of rotaviruses into SG I, SG II, SG I+II and SG non-I-non-II. The
      non-structural protein 4 (NSP4) encoded by segment 10 has a role in viral
      morphogenesis and five genetic groups have been described, NSP4 genotypes A-E.
      The aim of this investigation was to characterize the NSP4 and VP6 genes of
      rotavirus strains recovered from hospitalized children. Thirty rotavirus strains
      were submitted to RT-PCR followed by sequencing and phylogenetic analysis. Among
      the different G and P genotype combinations, two distinct genetic groups could be
      recognized for the NSP4 gene. Twenty-eight clustered with NSP4 genotype B. The
      two P[4]G2 strains fell into NSP4 genotype A and clustered distinctly, with a 100
      % bootstrap value. The strains distinguished within a group were closely related
      to each other at the nucleotide and amino acid levels. A phylogenetic tree was
      constructed for the VP6 gene including the human strains RMC100, E210, Wa, US1205
      and 1076, and the animal strains Gott, NCDV, SA-11, FI-14 and EW. This is the
      first report on Brazilian rotavirus strains describing NSP4 genotype A strains
      associated with VP6 SG I, and NSP4 genotype B strains associated with VP6 SG II.

PMID- 17510275
TI  - Prosthetic valve endocarditis due to Neisseria elongata subsp. elongata in a
      patient with Klinefelter's syndrome.
AB  - A case is reported of prosthetic valve endocarditis due to Neisseria elongata
      subsp. elongata in a patient with Klinefelter's syndrome. This is believed to be
      only the third case of endocarditis reported due to this subspecies. N. elongata
      is difficult to identify, and is morphologically and biochemically similar to
      Kingella spp. Sequencing of the 16S rRNA gene is useful for identification. The
      patient was successfully treated with amoxicillin and gentamicin, followed by
      ceftriaxone.

PMID- 17510276
TI  - Recurrent infection with genetically identical pneumococcal isolates in a patient
      with interleukin-1 receptor-associated kinase-4 deficiency.
AB  - Interleukin-1 receptor-associated kinase (IRAK)-4 deficiency is a rare primary
      immunodeficiency disorder characterized by severe, invasive infections with
      Streptococcus pneumoniae. Using the PFGE technique a genetic linkage was found
      between two S. pneumoniae serotype 14 isolates causing arthritis and meningitis
      at 3 and 5(1/2) years of age, respectively, in a boy with IRAK-4 deficiency. This
      finding suggested that patients with IRAK-4 deficiency may harbour persistent
      strains of pneumococci. Alternatively, reinfection with strains from close
      contacts of the patient might cause recurrent invasive disease. It is proposed
      that eradication of pneumococci from the nasopharynx, and immunization of
      household contacts may prevent recurrent infection in IRAK-4-deficient patients.

PMID- 17510277
TI  - Meticillin-resistant Staphylococcus aureus clones with distinct clinical and
      microbiological features in a Korean community.

PMID- 17510278
TI  - Madurella mycetomatis compounds cross-reactive with galactomannan are detectable
      in culture supernatant but not in serum.

PMID- 17510279
TI  - Molecular identification by random amplified polymorphic DNA analysis of a pseudo
      outbreak of Mycobacterium fortuitum due to cross-contamination of clinical
      samples.

PMID- 17510280
TI  - Application of rapid dot-ELISA for antibody detection of leptospirosis.

PMID- 17510281
TI  - Methodological and dispositional predictors of congruence between implicit and
      explicit need for achievement.
AB  - In this research, the authors questioned the statistical independence of implicit
      and explicit motives. Their first aim was to identify a methodological factor
      that may have weakened implicit-explicit motive correlations in past research.
      Their second aim was to identify personality traits that moderate implicit
      explicit motive congruence. They found that implicit and explicit need for
      achievement (nAch) are significantly correlated, but only if the implicit and
      explicit measures are matched in content. Three traits were found to uniquely
      moderate the relationship between implicit and explicit nAch: private body
      consciousness, self-monitoring, and preference for consistency. These findings
      indicate that implicit and explicit nAch are systematically related and suggest
      that some individuals may use implicit nAch as a foundation for the development
      of explicit nAch.

PMID- 17510282
TI  - Unphosphorylated STAT3 accumulates in response to IL-6 and activates
      transcription by binding to NFkappaB.
AB  - gp130-linked cytokines such as interleukin-6 (IL-6) stimulate the formation of
      tyrosine-phosphorylated signal transducer and activator of transcription 3 (P
      STAT3), which activates many genes, including the STAT3 gene itself. The
      resulting increase in the concentration of unphosphorylated STAT3 (U-STAT3)
      drives a second wave of expression of genes such as RANTES, IL6, IL8, MET, and
      MRAS that do not respond directly to P-STAT3. Thus, U-STAT3 sustains cytokine
      dependent signaling at late times through a mechanism completely distinct from
      that used by P-STAT3. Many U-STAT3-responsive genes have kappaB elements that are
      activated by a novel transcription factor complex formed when U-STAT3 binds to
      unphosphorylated NFkappaB (U-NFkappaB), in competition with IkappaB. The U
      STAT3/U-NFkappaB complex accumulates in the nucleus with help from the nuclear
      localization signal of STAT3, activating a subset of kappaB-dependent genes.
      Additional genes respond to U-STAT3 through an NFkappaB-independent mechanism.
      The role of signal-dependent increases in U-STAT3 expression in regulating gene
      expression is likely to be important in physiological responses to gp130-linked
      cytokines and growth factors that activate STAT3, and in cancers that have
      constitutively active P-STAT3.

PMID- 17510283
TI  - An ortholog of the Ro autoantigen functions in 23S rRNA maturation in D.
      radiodurans.
AB  - In both animal cells and the eubacterium Deinococcus radiodurans, the Ro
      autoantigen, a ring-shaped RNA-binding protein, associates with small RNAs called
      Y RNAs. In vertebrates, Ro also binds the 3' ends of misfolded RNAs and is
      proposed to function in quality control. However, little is known about the
      function of Ro and the Y RNAs in vivo. Here, we report that the D. radiodurans
      ortholog Rsr (Ro sixty related) functions with exoribonucleases in 23S rRNA
      maturation. During normal growth, 23S rRNA maturation is inefficient, resulting
      in accumulation of precursors containing 5' and 3' extensions. During growth at
      elevated temperature, maturation is efficient and requires Rsr and the
      exoribonucleases RNase PH and RNase II. Consistent with the hypothesis that Y
      RNAs inhibit Ro activity, maturation is efficient at all temperatures in cells
      lacking the Y RNA. In the absence of Rsr, 23S rRNA maturation halts at positions
      of potential secondary structure. As Rsr exhibits genetic and biochemical
      interactions with the exoribonuclease polynucleotide phosphorylase, Rsr likely
      functions in an additional process with this nuclease. We propose that Rsr
      functions as a processivity factor to assist RNA maturation by exoribonucleases.
      This is the first demonstration of a role for Ro and a Y RNA in vivo.

PMID- 17510284
TI  - Treadmilling of a prokaryotic tubulin-like protein, TubZ, required for plasmid
      stability in Bacillus thuringiensis.
AB  - Prokaryotes rely on a distant tubulin homolog, FtsZ, for assembling the
      cytokinetic ring essential for cell division, but are otherwise generally thought
      to lack tubulin-like polymers that participate in processes such as DNA
      segregation. Here we characterize a protein (TubZ) from the Bacillus
      thuringiensis virulence plasmid pBtoxis, which is a member of the tubulin/FtsZ
      GTPase superfamily but is only distantly related to both FtsZ and tubulin. TubZ
      assembles dynamic, linear polymers that exhibit directional polymerization with
      plus and minus ends, movement by treadmilling, and a critical concentration for
      assembly. A point mutation (D269A) that alters a highly conserved catalytic
      residue within the T7 loop completely eliminates treadmilling and allows the
      formation of stable polymers at a much lower protein concentration than the wild
      type protein. When expressed in trans, TubZ(D269A) coassembles with wild-type
      TubZ and significantly reduces the stability of pBtoxis, demonstrating a direct
      correlation between TubZ dynamics and plasmid maintenance. The tubZ gene is in an
      operon with tubR, which encodes a putative DNA-binding protein that regulates
      TubZ levels. Our results suggest that TubZ is representative of a novel class of
      prokaryotic cytoskeletal proteins important for plasmid stability that diverged
      long ago from the ancient tubulin/FtsZ ancestor.

PMID- 17510285
TI  - Autophagy suppresses tumor progression by limiting chromosomal instability.
AB  - Autophagy is a bulk degradation process that promotes survival under metabolic
      stress, but it can also be a means of cell death if executed to completion.
      Monoallelic loss of the essential autophagy gene beclin1 causes susceptibility to
      metabolic stress, but also promotes tumorigenesis. This raises the paradox that
      the loss of a survival pathway enhances tumor growth, where the exact mechanism
      is not known. Here, we show that compromised autophagy promoted chromosome
      instability. Failure to sustain metabolism through autophagy was associated with
      increased DNA damage, gene amplification, and aneuploidy, and this genomic
      instability may promote tumorigenesis. Thus, autophagy maintains metabolism and
      survival during metabolic stress that serves to protect the genome, providing an
      explanation for how the loss of a survival pathway leads to tumor progression.
      Identification of this novel role of autophagy may be important for rational
      chemotherapy and therapeutic exploitation of autophagy inducers as potential
      chemopreventive agents.

PMID- 17510287
TI  - P-wave dispersion in panic disorder.
AB  - BACKGROUND: P-wave dispersion (PWD) is defined as the difference between the
      maximum and the minimum P-wave (Pmax and Pmin, respectively) duration.
      Significant variation in cardiac atrial PWD has been correlated with changes in
      systemic autonomic tone such as during periods of anxiety. It is also known that
      the degree of PWD seen on 12-lead electrocardiogram (ECG) may be a predictor of
      susceptibility of the atrial myocardium to future atrial fibrillation (AF).
      Therefore, we firstly aimed to show an association between PWD and panic
      disorder, a state of high sympathetic tone. METHODS: PWD was measured in 40
      outpatients with panic disorder and in 40 physically and mentally healthy age-
      and gender-matched controls. In addition, the Panic Agoraphobia Scale (PAS) and
      the Hamilton Depression Rating Scale (HDRS) were scored concomitantly. RESULTS:
      Both Pmax and Pmin were significantly higher than those of healthy controls. PWD
      was significantly greater in the panic disorder group than in the controls. As
      expected, the mean score on PAS was significantly higher for the panic disorder
      group than for the controls and correlated significantly with PWD. Heart rate
      (measured as RR intervals in milliseconds on electrocardiogram) did not differ
      significantly between the groups. CONCLUSIONS: The findings of the present study
      suggest that the disorder may be associated with an increase in PWD. This
      association may result from prolonged anxiety and increase in sympathetic
      modulation, which are main characteristics of panic disorder.

PMID- 17510288
TI  - Consistent association between mixed lateral preference and PTSD: confirmation
      among a national study of 2490 US Army Vietnam veterans.
AB  - OBJECTIVE: To evaluate the research-based association between mixed lateral
      preference for handedness and risk for posttraumatic stress disorder (PTSD) in a
      large-scale sample of US Army Vietnam veterans exposed to war zone stressors.
      METHOD: We used a national sample of 2490 male US Army veterans, who completed
      the Edinburgh Handedness Inventory (EHI), a measure ranging from -100 (pure left
      handedness) to +100 (pure right-handedness). We developed several classifications
      representing levels of mixed laterality: a) an EHI -70 to +70 (EHI 70, moderate
      mixed); b) an EHI -50 to +50 (EHI 50, consistent mixed); and c) an EHI 0, plus
      reports of using either hand on > or =50% of the tasks assessed (EHI 0+, extreme
      mixed). We controlled for intelligence, race, Army entry age, and Army volunteer
      status, and we assessed the impact of combat exposure. RESULTS: Although all
      three handedness measures were associated with current PTSD in bivariate
      analyses, only Edinburgh 0+ was associated with PTSD in the multivariate model
      (odds ratio (OR) = 2.1; p = .021). However, when we classified handedness by high
      combat exposure, all three measures were associated with PTSD, with ORs = 2.5,
      2.8, and 4.7 for EHI 70, EHI 50, and EHI 0+, respectively (all p < .001).
      Veterans with mixed laterality and high combat exposure also had significantly
      increased PTSD symptoms (all p < .001). CONCLUSION: Our study confirmed findings
      reported among mostly smaller clinical samples and suggested that mixed lateral
      preference was associated with PTSD, especially among those individuals exposed
      to more severe psychological trauma.

PMID- 17510286
TI  - Effects of RAS on the genesis of embryonal rhabdomyosarcoma.
AB  - Embryonal rhabdomyosarcoma (ERMS) is a devastating cancer with specific features
      of muscle differentiation that can result from mutational activation of RAS
      family members. However, to date, RAS pathway activation has not been reported in
      a majority of ERMS patients. Here, we have created a zebrafish model of RAS
      induced ERMS, in which animals develop externally visible tumors by 10 d of life.
      Microarray analysis and cross-species comparisons identified two conserved gene
      signatures found in both zebrafish and human ERMS, one associated with tumor
      specific and tissue-restricted gene expression in rhabdomyosarcoma and a second
      comprising a novel RAS-induced gene signature. Remarkably, our analysis uncovered
      that RAS pathway activation is exceedingly common in human RMS. We also created a
      new transgenic coinjection methodology to fluorescently label distinct
      subpopulations of tumor cells based on muscle differentiation status. In
      conjunction with fluorescent activated cell sorting, cell transplantation, and
      limiting dilution analysis, we were able to identify the cancer stem cell in
      zebrafish ERMS. When coupled with gene expression studies of this cell
      population, we propose that the zebrafish RMS cancer stem cell shares similar
      self-renewal programs as those found in activated satellite cells.

PMID- 17510289
TI  - Facets of openness predict mortality in patients with cardiac disease.
AB  - OBJECTIVE: To examine the NEO Personality Inventory (NEO PI) Openness to
      Experience (O) domain and its facets as predictors of cardiac deaths and all
      cause mortality. METHODS: The NEO PI was administered to a sample of 977 coronary
      catheterization patients with significant coronary artery disease. Over an
      average 15-year follow-up period, 266 cardiac deaths and 463 total deaths
      occurred. The relationships of O scores to mortality were examined with Cox
      proportional hazard models. Each model included age, left ventricular ejection
      fraction, severity of congestive heart failure, and number of diseased vessels as
      covariates. RESULTS: The O domain score was not associated with all-cause
      mortality and only approached significance for decreased cardiac deaths (p =
      .055). However, a higher score for Openness to Feelings was associated with a
      decreased risk of cardiac death (p < .01) and all-cause mortality (p < .01). High
      Openness to Actions was also associated with decreased cardiac mortality (p <
      .01) and all-cause mortality (p = .03) risk. Higher Openness to Aesthetics and
      Ideas were only associated with decreased cardiac death risk (both p values
      <.04). In contrast, Openness to Fantasy and Values were not associated with
      longevity. Previous evidence suggested that educational achievement may account
      for the effects of Openness to Experience on mortality; however, controlling for
      educational achievement did not change the results. CONCLUSION: These findings
      suggest that greater emotional awareness and high curiosity, as indicated by the
      NEO PI Feelings and Actions facets, are associated with increased patient
      longevity independently of other risk factors and educational achievement.

PMID- 17510291
TI  - Bivariate genetic modeling of cardiovascular stress reactivity: does stress
      uncover genetic variance?
AB  - OBJECTIVE: To test the existence of gene-by-stress interaction by assessing
      cardiovascular stress reactivity in monozygotic and dizygotic twins. METHODS: We
      studied 160 adolescent (mean age 16.7 +/- 2.0 years; range 13-22 years) and 212
      middle-aged twin pairs (mean age 44.2 +/- 6.7 years; range 34-63 years). Systolic
      (SBP) and diastolic (DBP) blood pressure, heart rate (HR), pre-ejection period
      (PEP), and respiratory sinus arrhythmia (RSA) were measured at rest and during a
      choice reaction time and a mental arithmetic task. We used a bivariate analysis
      of the resting and mean stress levels to test for gene-by-stress interaction,
      which can be caused by the emergence of new genetic variance specific to stress
      or by stress-induced amplification of the existing genetic variance at rest.
      RESULTS: Genetic factors significantly contributed to individual differences in
      resting SBP, DBP, HR, PEP, and RSA levels in the adolescent (heritability range
      0.31-0.70) and middle-aged (heritability range 0.32-0.64) cohorts. The effect of
      these genetic factors was amplified by stress for all variables in the adolescent
      cohort, and for SBP in the middle-aged cohort. In addition, stress-specific
      genetic variation emerged for HR in both cohorts and for PEP and SBP in the
      adolescent cohort. Heritability of stress levels of SBP, DBP, HR, PEP, and RSA
      ranged from 0.54 to 0.74 in the adolescents and from 0.44 to 0.64 in the middle
      aged cohort. CONCLUSIONS: Stress uncovers genetic variance in BP, HR, and cardiac
      sympathovagal balance through the emergence of new stress-specific genetic
      effects and the amplification of existing genetic effects that also affect the
      resting values.

PMID- 17510290
TI  - Self-efficacy and health status in patients with coronary heart disease: findings
      from the heart and soul study.
AB  - OBJECTIVE: To examine the relationship between cardiac self-efficacy and health
      status, including symptom burden, physical limitation, quality of life, and
      overall health among outpatients with stable coronary heart disease (CHD). We
      hypothesized that lower self-efficacy would predict worse health status,
      independent of CHD severity and depression. METHODS: We performed a cross
      sectional study of 1024 outpatients with CHD, who were recruited between 2000 and
      2002 for the Heart and Soul Study. We administered a validated measure of cardiac
      self-efficacy, assessed cardiac function using exercise treadmill testing with
      stress echocardiography, and measured depressive symptoms using the Patient
      Health Questionnaire. Health status outcomes (symptom burden, physical
      limitation, and quality of life) were assessed using the Seattle Angina
      Questionnaire, and overall health was measured as fair or poor (versus good, very
      good, or excellent). RESULTS: After adjustment for CHD severity and depressive
      symptoms, each standard deviation (4.5-point) decrease in self-efficacy score was
      independently associated with greater symptom burden (adjusted odds ratio (OR) =
      2.1, p = .001), greater physical limitation (OR = 1.8, p < .0001), worse quality
      of life (OR = 1.6, p < .0001), and worse overall health (OR = 1.9, p < .0001).
      Depressive symptoms and poor treadmill exercise capacity were also associated
      with poor health status, but left ventricular ejection fraction and ischemia were
      not. CONCLUSIONS: Among patients with CHD, low cardiac self-efficacy is
      associated with poor health status, independent of CHD severity and depressive
      symptoms. Further study should examine if self-efficacy constitutes a useful
      target for cardiovascular disease management interventions.

PMID- 17510292
TI  - Prevalence of major psychiatric illness in young adults who were burned as
      children.
AB  - OBJECTIVE: To determine the prevalence of major psychiatric illness in a group of
      young adults who suffered significant burn injury as children. METHOD: A total of
      101 persons (58 males, 43 females), aged 21 +/- 2.6 years, 14.0 +/- 5.4 years
      postburn of 54% +/- 20% total body surface area, were assessed for serious past
      and present mental illness by using a Structured Clinical Interview (SCID) for
      Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) Axis
      I diagnoses. RESULTS: The SCID findings demonstrated that the prevalence of any
      Axis I major mental illness was 45.5% for the past month (current) and 59.4% for
      lifetime. These rates of overall disorder and the rates for most specific
      disorders were significantly higher than those found in the US population of
      comparable age. Logistic regression was used to examine demographic and burn
      characteristics as predictors of current and lifetime psychiatric disorder within
      the burn survivor sample. The female gender was significantly associated with
      higher rates of any current disorder. Other demographic and burn characteristics
      were not significantly related to the overall prevalence of current or lifetime
      disorder. Only a small number of those with disorders reported any current mental
      health treatment. CONCLUSIONS: Significant burn injury as a child leads to an
      increased risk of developing a major mental illness. Young adults who suffered
      major burn injury as children should be screened for these illnesses to initiate
      appropriate treatment.

PMID- 17510293
TI  - Impact of socioeconomic status on physiological health in adolescents: an
      experimental manipulation of psychosocial factors.
AB  - OBJECTIVE: To examine the effects of a brief psychosocial manipulation on
      physiological responses to laboratory stress in lower and higher socioeconomic
      status (SES) adolescents. METHODS: A total of 115 adolescents participated in two
      acute laboratory stress tasks: one with psychosocial intervention and one with no
      intervention. In the intervention condition, half of the adolescents were given
      control over the stressor parameters; the other half received social
      informational resources (hints provided by another person) for dealing with the
      stressor. Physiological reactivity was monitored. RESULTS: Lower SES adolescents
      exhibited less physiological reactivity when provided with intervention compared
      with no intervention. Within the lower SES group, the resource condition reduced
      physiological reactivity more than the control condition did. Higher SES
      adolescents did not respond physiologically to intervention. CONCLUSIONS: This
      study provides a preliminary illustration of an experimental laboratory approach
      to studying SES-health relationships and suggests that providing informational
      support during a stressor may have beneficial implications for the physiological
      health of lower SES adolescents.

PMID- 17510294
TI  - Quality of life, depressed mood, and self-esteem in adolescents with heart
      disease.
AB  - OBJECTIVE: To assess health-related quality of life (HRQoL), depressed mood, and
      self-esteem in adolescents with heart disease and compare them with age-matched
      healthy adolescents (control group). METHODS: Ninety adolescents (aged 12 to 18
      years with congenital or acquired heart disease) and 87 controls completed the
      HRQoL (TAAQOL-CHD), Center for Epidemiologic Studies Depression scale, and
      Rosenberg self-esteem questionnaires. Relevant medical details were collected.
      The patients and their parents were asked to rate their perceived severity of
      heart disease. RESULTS: Adolescents with severe heart disease reported higher
      levels of depressed mood and lower self-esteem than did adolescents with moderate
      and mild heart disease and age-matched healthy controls. Adolescents with severe
      heart disease also reported worse HRQoL than those with moderate and mild
      disease. According to the multiple regression analysis, 44% of variance of HRQoL
      was explained by the study variables. Disease severity alone explained 11% of the
      variance, but when entered with the other study variables, depressed mood, self
      esteem, and adolescents' perceived severity of disease were the only significant
      contributors to the explained variance of HRQoL. An exploratory mediation
      analysis, using the Sobel test, was therefore applied, and it showed that
      depressed mood and perceived disease severity, but not self-esteem, mediated the
      relationship between disease severity and HRQoL. CONCLUSIONS: Lower HRQoL was
      found in adolescents with severe heart disease. Psychosocial factors have a
      significant effect on the psychological state of adolescents, and they should be
      addressed and treated.

PMID- 17510295
TI  - Intracellular signaling required for CCL25-stimulated T cell adhesion mediated by
      the integrin alpha4beta1.
AB  - The alpha4beta1 integrin is expressed on thymocytes and mediates cell attachment
      to its ligands CS-1/fibronectin (CS-1/FN) and VCAM-1 in the thymus. The chemokine
      CCL25 is highly expressed in the thymus, where it binds to its receptor CCR9 on
      thymocytes promoting migration and activation. We show here that alpha4beta1 and
      CCR9 are coexpressed mainly on double- and single-positive thymocytes and that
      CCL25 strongly stimulates CD4(+)CD8(+) and CD4(+)CD8(-) adhesion to CS-1/FN and
      VCAM-1. CCL25 rapidly activated the GTPases Rac and Rap1 on thymocytes, and this
      activation was required for stimulation of adhesion, as detected using the
      CCR9(+)/alpha4beta1(+) human T cell line Molt-4. To study the role on CCL25
      stimulated adhesion of the Rac downstream effector Wiskott-Aldrich syndrome
      protein family verproline-homologous protein 2 (WAVE2) as well as of Rap1-GTP
      interacting proteins, regulator of adhesion and cell polarization enriched in
      lymphoid tissues (RAPL) and Rap1-GTP-interacting adapter molecule (RIAM), we
      knocked down their expression and tested transfectant attachment to alpha4beta1
      ligands. We found that WAVE2 and RAPL but not RIAM were required for efficient
      triggering by CCL25 of T cell adhesion to CS-1/FN and VCAM-1. Although Rac and
      Rap1 activation was required during early steps of T cell adhesion stimulated by
      CCL25, WAVE2 was needed for the development of actin-dependent T cell spreading
      subsequent to adhesion strengthening but not during initial alpha4beta1-ligand
      interactions. These results suggest that regulation by CCL25 of adhesion of
      thymocyte subpopulations mediated by alpha4beta1 could contribute to control
      their trafficking in the thymus during maturation, and identify Rac-WAVE2 and
      Rap1-RAPL as pathways whose activation is required in inside-out signaling,
      leading to stimulated adhesion.

PMID- 17510296
TI  - Role of ADAM17 in the ectodomain shedding of TNF-alpha and its receptors by
      neutrophils and macrophages.
AB  - TNF-alpha and its receptors TNFRI and TNFRII are cleaved from the surface of
      leukocytes by a proteolytic process referred to as ectodomain shedding. The role
      of a disintegrin and metalloproteinase 17 (ADAM17) in this process by the major
      professional phagocytes neutrophils and macrophages, the primary producers of TNF
      alpha during inflammation induction, is based entirely on indirect evidence, and
      other sheddases have been implicated as well. As Adam17 gene-targeting in mice is
      lethal, we assessed the protease's relative contribution to TNF-alpha, TNFRI, and
      TNFRII shedding using radiation chimeric mice with leukocytes lacking functional
      ADAM17. We report ablated, soluble TNF-alpha, TNFRI, and TNFRII production by
      neutrophils and macrophages stimulated with various microbial antigens and
      greatly reduced TNF-alpha levels in vivo following inflammation induction. This
      is the first simultaneous analysis of TNF-alpha, TNFRI, and TNFRII shedding by
      neutrophils and macrophages and the first direct evidence that ADAM17 is a
      primary and nonredundant sheddase.

PMID- 17510297
TI  - Motor unit composition has little effect on the short-range stiffness of feline
      medial gastrocnemius muscle.
AB  - Studies on skinned fibers and single motor units have indicated that slow-twitch
      fibers are stiffer than fast-twitch fibers. This suggests that skeletal muscles
      with different motor unit compositions may have different short-range stiffness
      (SRS) properties. Furthermore, the natural recruitment of slow before fast motor
      units may result in an SRS-force profile that is different from electrical
      stimulation. However, muscle architecture and the mechanical properties of
      surrounding tissues also contribute to the net SRS of a muscle, and it remains
      unclear how these structural features each contribute to the SRS of a muscle. In
      this study, the SRS-force characteristics of cat medial gastrocnemius muscle were
      measured during natural activation using the crossed-extension reflex, which
      activates slow before fast motor units, and during electrical activation, in
      which all motor units are activated synchronously. Short, rapid, isovelocity
      stretches were applied using a linear puller to measure SRS across the range of
      muscle forces. Data were collected from eight animals. Although there was a trend
      toward greater stiffness during natural activation, this trend was small and not
      statistically significant across the population of animals tested. A simple
      model, in which the slow-twitch fibers were assumed to be 30% stiffer than the
      fast-twitch fibers, was used to simulate the experimental results. Experimental
      and simulated results show that motor unit composition or firing rate has little
      effect on the SRS property of the cat MG muscle, suggesting that architectural
      features may be the primary determinant of SRS.

PMID- 17510298
TI  - Systemic hypoxia causes cutaneous vasodilation in healthy humans.
AB  - Hypoxia and hypercapnia represent special challenges to homeostasis because of
      their effects on sympathetic outflow and vascular smooth muscle. In the cutaneous
      vasculature, even small changes in perfusion can shift considerable blood volume
      to the periphery and thereby impact both blood pressure regulation and
      thermoregulation. However, little is known about the influence of hypoxia and
      hypercapnia on this circulation. In the present study, 35 healthy subjects were
      instrumented with two microdialysis fibers in the ventral forearm. Each site was
      continuously perfused with saline (control) or bretylium tosylate (10 mM) to
      prevent sympathetically mediated vasoconstriction. Skin blood flow was assessed
      at each site (laser-Doppler flowmetry), and cutaneous vascular conductance (CVC)
      was calculated as red blood cell flux/mean arterial pressure and normalized to
      baseline. In 13 subjects, isocapnic hypoxia (85 and 80% O(2) saturation)
      increased CVC to 120 +/- 10 and 126 +/- 7% baseline in the control site (both P <
      0.05) and 113 +/- 3 (P = 0.087) and 121 +/- 4% baseline (P < 0.05) in the
      bretylium site. Adrenergic blockade did not affect the magnitude of this response
      (P > 0.05). In nine subjects, hyperpnea (matching hypoxic increases in tidal
      volume) caused no change in CVC in either site (both P > 0.05). In 13 subjects,
      hypercapnia (+5 and +9 Torr) increased CVC to 111 +/- 4 and 111 +/- 4% baseline,
      respectively, in the control site (both P < 0.05), whereas the bretylium site
      remained unchanged (both P > 0.05). Thus both hypoxia and hypercapnia cause
      modest vasodilation in nonacral skin. Adrenergic vasoconstriction of neural
      origin does not restrain hypoxic vasodilation, but may be important in
      hypercapnic vasodilation.

PMID- 17510299
TI  - Raising end-expiratory volume relieves air hunger in mechanically ventilated
      healthy adults.
AB  - Air hunger is an unpleasant urge to breathe and a distressing respiratory symptom
      of cardiopulmonary patients. An increase in tidal volume relieves air hunger,
      possibly by increasing pulmonary stretch receptor cycle amplitude. The purpose of
      this study was to determine whether increasing end-expiratory volume (EEV) also
      relieves air hunger. Six healthy volunteers (3 women, 31 +/- 4 yr old) were
      mechanically ventilated via a mouthpiece (12 breaths/min, constant end-tidal
      Pco(2)) at high minute ventilation (Ve; 12 +/- 2 l/min, control) and low Ve (6 +/
      1 l/min, air hunger). EEV was raised to approximately 150, 400, 725, and 1,000
      ml by increasing positive end-expiratory pressure (PEEP) to 2, 4, 6, and 8
      cmH(2)O, respectively, for 1 min during high and low Ve. The protocol was
      repeated with the subjects in the seated and supine positions to test for the
      effect of shifting baseline EEV. Air hunger intensity was rated at the end of
      each breath on a visual analog scale. The increase in EEV was the same in the
      seated and supine positions; however, air hunger was reduced to a greater extent
      in the seated position (13, 30, 31, and 44% seated vs. 3, 9, 23, and 27% supine
      at 2, 4, 6, and 8 cmH(2)O PEEP, respectively, P < 0.05). Removing PEEP produced a
      slight increase in air hunger that was greater than pre-PEEP levels (P < 0.05).
      Air hunger is relieved by increases in EEV and tidal volume (presumably via an
      increase in mean pulmonary stretch receptor activity and cycle amplitude,
      respectively).

PMID- 17510300
TI  - Responsiveness of the isolated airway during simulated deep inspirations: effect
      of airway smooth muscle stiffness and strain.
AB  - In vivo, breathing movements, including tidal and deep inspirations (DIs), exert
      a number of beneficial effects on respiratory system responsiveness in healthy
      humans that are diminished or lost in asthma, possibly as a result of reduced
      distension (strain) of airway smooth muscle (ASM). We used bronchial segments
      from pigs to assess airway responsiveness under static conditions and during
      simulated tidal volume oscillations with and without DI and to determine the
      roles of airway stiffness and ASM strain on responsiveness. To simulate airway
      dilations during breathing, we cycled the luminal volume of liquid-filled
      segments. Volume oscillations (15 cycles/min) were set so that, in relaxed
      airways, they produced a transmural pressure increase of approximately 5-10
      cmH(2)O for tidal maneuvers and approximately 5-30 cmH(2)O for DIs. ACh dose
      response curves (10(-7)-3 x 10(-3) M) were constructed under static and dynamic
      conditions, and maximal response and sensitivity were determined. Airway
      stiffness was measured from tidal trough-to-peak pressure and volume cycles. ASM
      strain produced by DI was estimated from luminal volume, airway length, and inner
      wall area. DIs produced substantial ( approximately 40-50%) dilation, reflected
      by a decrease in maximal response (P < 0.001) and sensitivity (P < 0.05).
      However, the magnitude of bronchodilation decreased significantly in proportion
      to airway stiffening caused by contractile activation and an associated reduction
      in ASM strain. Tidal oscillations, in comparison, had little effect on
      responsiveness. We conclude that DI regulates airway responsiveness at the airway
      level, but this is limited by airway stiffness due to reduced ASM strain.

PMID- 17510301
TI  - Rapid 2nd-tier test for measurement of 3-OH-propionic and methylmalonic acids on
      dried blood spots: reducing the false-positive rate for propionylcarnitine during
      expanded newborn screening by liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: The expansion of newborn screening programs has increased the number
      of newborns diagnosed with inborn errors of metabolism in the presymptomatic
      phase, but it has also increased the number of costly, stress-producing false
      positive results. Because propionylcarnitine (C3) is one of the analytes most
      frequently responsible for false-positive results, we aimed to develop a rapid
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to identify free
      methylmalonic (MMA) and 3-OH propionic (3OH-PA) acids in blood spots. METHODS: We
      studied newborn screening spots from 250 healthy controls; 124 from infants with
      abnormal C3, of whom only 5 (4%) were truly affected; 124 from infants with
      altered isolated methylmalonylcarnitine; and 4 from clinically diagnosed
      patients. Whole blood was eluted from a 3.2-mm dried blood spot by a
      CH(3)CN/H(2)O 7:3 and 5 mL/L formic. This extract was injected into a LC-MS/MS
      equipped with pneumatically assisted electrospray without derivatization. Total
      analysis time was 5 min per sample. RESULTS: The assays were linear up to 3300
      nmol/L for both metabolites. Intra- and interassay imprecision data were 3.6%-8%
      and 3.1%-6%, respectively, for MMA and 5.2%-20% and 3.6%-17% for 3OH-PA. Limit of
      detection and limit of quantitation were 1.95 and 4.2 micromol/L, respectively,
      for MMA and 8 and 10 micromol/L for 3OH-PA. The recoveries were 92.9%-106.1%. No
      deterioration was noted on the columns after 500 chromatographic runs. If the new
      method had been used as a 2nd-tier test for the 124 samples, only the 5 true
      positives would have been recalled for additional samples, and the positive
      predictive value would have been 100%. CONCLUSIONS: This method has the potential
      to markedly reduce false-positive results and the associated costs and anxiety.
      It may also be suitable for diagnosing and routinely monitoring blood spots for
      methylmalonic aciduria and propionic acidemia.

PMID- 17510302
TI  - Multiplex assay for comprehensive genotyping of genes involved in drug
      metabolism, excretion, and transport.
AB  - BACKGROUND: Drug metabolism is a multistep process by which the body disposes of
      xenobiotic agents such as therapeutic drugs. Genetic variation in the enzymes
      involved in this process can lead to variability in a patient's response to
      medication. METHODS: We used molecular-inversion probe technology to develop a
      multiplex genotyping assay that can simultaneously test for 1227 genetic variants
      in 169 genes involved in drug metabolism, excretion, and transport. Within this
      larger set of variants, we performed analytical validation of a clinically
      defined core set of 165 variants in 27 genes to assess accuracy, imprecision, and
      dynamic range. RESULTS: In a test set of 91 samples, genotyping accuracy for the
      core set probes was 99.8% for called genotypes, with a 1.2% no-call (NC) rate.
      The majority of the core set probes (133 of 165) had < or = 1 genotyping failure
      in the test set; a subset of 12 probes was responsible for the majority of
      failures (mainly NC). Genotyping results were reproducible upon repeat testing
      with overall within- and between-run variation of 1.1% and 1.4%, respectively
      again, primarily NCs in a subset of probes. The assay showed stable genotyping
      results over a 6-fold range of input DNA. CONCLUSIONS: This assay generates a
      comprehensive assessment of a patient's metabolic genotype and is a tool that can
      provide a more thorough understanding of patient-to-patient variability in
      pharmacokinetic responses to drugs.

PMID- 17510303
TI  - High-throughput quantitative profiling of serum N-glycome by MALDI-TOF mass
      spectrometry and N-glycomic fingerprint of liver fibrosis.
AB  - BACKGROUND: The use of MALDI-TOF mass spectrometry (MS) in quantitative glycan
      profiling has not been reported. In this study, we attempted to establish a high
      throughput quantitative assay for profiling serum N-glycome, and we applied the
      new assay to identifying serum N-glycans for diagnosis of liver fibrosis and
      cirrhosis. METHODS: N-glycans from whole serum proteins in 2 microL serum were
      released by enzymatic digestion, cleaned up by hydrophilic chromatography, and
      subsequently quantitatively profiled with a linear MALDI-TOF MS system, which was
      originally designed for quantitative proteomic profiling. Serum N-glycome
      profiles from 46 patients with chronic hepatitis B infection and with different
      degrees of liver fibrosis were examined. RESULTS: The intra- and interassay CVs
      of peak intensities of the standard N-glycans were <8% and <17%, respectively.
      When the assay was applied to the analysis of serum N-glycome profiles, 17 peaks
      were found to be potential biomarkers for detection of liver fibrosis/cirrhosis.
      Linear regression analysis revealed that 4 peaks of 1341.5, 1829.7, 1933.3, and
      2130.3 m/z (all P <0.005) had complementary value in detecting liver fibrosis and
      included them, but not any serological markers, in the diagnostic model. Leave
      one-out cross-validation showed the diagnostic model could identify significant
      fibrosis (Ishak score > or = 3) and cirrhosis (Ishak score > or = 5), both at 85%
      accuracy. CONCLUSION: This is the first study to illustrate the quantitative
      aspect of MALDI-TOF MS in N-glycome profiling and the first study to reveal the
      potential value of the serum N-glycan profile for identifying liver fibrosis.

PMID- 17510304
TI  - Magnetic control of an electrochemical microfluidic device with an arrayed
      immunosensor for simultaneous multiple immunoassays.
AB  - BACKGROUND: Methods based on magnetic bead probes have been developed for
      immunoassay, but most involve complicated labeling or stripping procedures and
      are unsuitable for routine use. METHODS: We synthesized magnet core/shell
      NiFe(2)O(4)/SiO(2) nanoparticles and fabricated an electrochemical magnetic
      controlled microfluidic device for the detection of 4 tumor markers. The
      immunoassay system consisted of 5 working electrodes and an Ag/AgCl reference
      electrode integrated on a glass substrate. Each working electrode contained a
      different antibody immobilized on the NiFe(2)O(4)/SiO(2) nanoparticle surface and
      was capable of measuring a specific tumor marker using noncompetitive
      electrochemical immunoassay. RESULTS: Under optimal conditions, the multiplex
      immunoassay enabled the simultaneous detection of 4 tumor markers. The sensor
      detection limit was <0.5 microg/L (or <0.5 kunits/L) for most analytes. Intra-
      and interassay imprecisions (CVs) were <4.5% and 8.7% for analyte concentrations
      >5 mug/L (or >5 kunits/L), respectively. No nonspecific adsorption was observed
      during a series of procedures to detect target proteins, and electrochemical
      cross-talk (CV) between neighboring sites was <10%. CONCLUSION: This immunoassay
      system offers promise for label-free, rapid, simple, cost-effective analysis of
      biological samples. Importantly, the chip-based immunosensor could be suitable
      for use in the mass production of miniaturized lab-on-a-chip devices and open new
      opportunities for protein diagnostics and biosecurity.

PMID- 17510305
TI  - High concentrations of soluble P-selectin are associated with risk of venous
      thromboembolism and the P-selectin Thr715 variant.
AB  - BACKGROUND: The cell adhesion molecule P-selectin has an important role in the
      pathophysiology of thrombosis. The effect on venous thromboembolism (VTE) of
      increased circulating concentrations of soluble P-selectin (sP-selectin) and
      their association with the P-selectin variant Thr715Pro is still uncertain.
      METHODS: This study was a case-control study of 116 patients with confirmed
      recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or
      pulmonary embolism, and 129 age- and sex-matched healthy individuals. We measured
      sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and
      sampled blood after a mean interval of 2.55 years after the most recent VTE
      event. RESULTS: The mean (SD) sP-selectin concentration was higher in patients
      than in controls: 47.3 (15.0) microg/L vs 36.8 (11.0) microg/L, P <0.001. The
      unadjusted odds ratio (OR) for sP-selectin >55.1 microg/L, representing the 95th
      percentile for controls, was 8.5 (95% CI, 3.7-23.3; P <0.001) and increased after
      adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor
      VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1-31.2; P <0.001). Pro715
      carriers were more prevalent among controls than patients (21.7% vs 14.7%). sP
      selectin concentrations were lower in this subgroup than in noncarriers: 31.3
      (7.9) microg/L vs 44.1 (14.1) microg/L; P <0.001). CONCLUSIONS: Increased sP
      selectin concentrations are associated with VTE and genotype status. sP-selectin
      concentrations are lower in individuals carrying the P-selectin Pro715 variant
      than in those without this variant.

PMID- 17510306
TI  - Microtransponder-based multiplex assay for genotyping cystic fibrosis.
AB  - BACKGROUND: We developed and evaluated a genotyping assay for detection of 50
      cystic fibrosis (CF) mutations. The assay is based on small (500 microm)
      electronic chips, radio frequency (RF) microtransponders (MTPs). The chips are
      analyzed on a unique fluorescence and RF readout instrument. METHODS: We divided
      the CF assay into 4 panels: core, Hispanic, African-American, and Caucasian. We
      amplified 18 CF transmembrane regulator (CFTR) DNA fragments covering 50
      mutations by use of multiplex PCR using 18 CFTR gene-specific primer pairs. PCR
      was followed by multiplex allele-specific primer extension (ASPE) reactions and
      hybridization to capture probes synthesized on MTPs. We used 100 ASPE primers and
      100 capture probes. We performed fluorescence measurements of hybridized MTP kits
      and assay analysis using a custom automated bench-top flow instrument. RESULTS:
      We validated the system by performing the assay on 23 commercial DNA samples in
      an internal study and 32 DNA samples in an external study. For internal and
      external studies, correct calls were 98.8% and 95.7%, false-positive calls 1.1%
      and 3.9%, and false-negative calls 0.12% and 0.36%, respectively. CONCLUSIONS:
      The MTP-based multiplex assay and analysis platform can be used for CF
      genotyping.

PMID- 17510307
TI  - Profiling the antibody immune response against blood stage malaria vaccine
      candidates.
AB  - BACKGROUND: The complexity and diversity of the antibody immune response to the
      antigen repertoire of a pathogen has long been appreciated. Although it has been
      recognized that the detection of antibodies against multiple antigens
      dramatically improves the clinical sensitivity and specificity of diagnostic
      assays, the prognostic value of serum reactivity profiles against multiple
      microbial antigens in protection has not been investigated. METHODS: Using
      malaria as a model we investigated whether antigen reactivity profiles in serum
      of children with different levels of clinical immunity to Plasmodium falciparum
      malaria correlated with protection. We developed a microarray immunoassay of 18
      recombinant antigens derived from 4 leading blood-stage vaccine candidates for P.
      falciparum [merozoite surface protein 1 (MSP1), MSP2, MSP3, and apical membrane
      antigen (AMA)-1]. Associations between observed reactivity profiles and clinical
      status were sought using k-means clustering and phylogenetic networks. RESULTS:
      The antibody immune response was unexpectedly complex, with different
      combinations of antigens recognized in different children. Serum reactivity to
      individual antigens did not correlate with immune status. By contrast, combined
      recognition of AMA-1 and allelic variants of MSP2 was significantly associated
      with protection against clinical malaria. This finding was confirmed
      independently by k-means clustering and phylogenetic networking. CONCLUSIONS: The
      analysis of reactivity profiles provides a wealth of novel information about the
      immune response against microbial organisms that would pass unnoticed in analysis
      of reactivity to antigens individually. Extension of this approach to a large
      fraction of the proteome may expedite the identification of correlates of
      protection and vaccine development against microbial diseases.

PMID- 17510308
TI  - Estimation of warfarin maintenance dose based on VKORC1 (-1639 G>A) and CYP2C9
      genotypes.
AB  - BACKGROUND: CYP2C9 polymorphisms are associated with decreased S-warfarin
      clearance and lower maintenance dosage. Decreased expression of VKORC1 resulting
      from the -1639G>A substitution has also been implicated in lower warfarin dose
      requirements. We investigated the additional contribution of this polymorphism to
      the variance in warfarin dose. METHODS: Sixty-five patients with stable
      anticoagulation were genotyped for CYP2C9 and VKORC1 with Tag-It allele-specific
      primer extension technology. Plasma S-warfarin concentrations and warfarin
      maintenance dose were compared among patients on the basis of the VKORC1 -1639G>A
      genotype. RESULTS: Eighty percent of CYP2C9*1/*1 patients stabilized on <4.0
      mg/day warfarin had at least 1 VKORC1 -1639A allele. Mean warfarin doses (SD)
      were 6.7 (3.3), 4.3 (2.2), and 2.7 (1.2) mg/day for patients with the VKORC1 
      1639GG, GA, and AA genotypes, respectively. Steady-state plasma concentrations of
      S-warfarin were lowest in patients with the VKORC1 -1639AA genotype and
      demonstrated a positive association with the VKORC1 -1639G allele copy number
      (trend P = 0.012). A model including VKORC1 and CYP2C9 genotypes, age, sex, and
      body weight accounted for 61% of the variance in warfarin daily maintenance dose.
      CONCLUSIONS: The VKORC1 -1639A allele accounts for low dosage requirements of
      most patients without a CYP2C9 variant. Higher plasma S-warfarin concentrations
      corresponding to increased warfarin maintenance dosages support a hypothesis for
      increased expression of the VKORC1 -1639G allele. VKORC1 and CYP2C9 genotypes,
      age, sex, and body weight account for the majority of variance in warfarin dose
      among our study population.

PMID- 17510309
TI  - p75 neurotrophin receptor inhibits invasion and metastasis of gastric cancer.
AB  - The p75 neurotrophin receptor (p75NTR) is a focus for study at present. However,
      its function in gastric cancer was not elucidated. Here, we investigated its
      relation with metastasis of gastric cancer. By immunohistochemistry, we found
      that the positive rate of p75NTR expression in metastatic gastric cancer was
      15.09% (16 of 106), which was lower compared with nonmetastatic gastric cancer
      (64.15%; 68 of 106). The average staining score in nonmetastatic gastric cancer
      was significantly higher than in metastatic gastric cancer (1.21 +/- 0.35 versus
      0.23 +/- 0.18; P<0.01). p75NTR protein level was also lowly expressed in the
      highly liver-metastatic gastric cancer cell line XGC9811-L compared with other
      gastric cancer cell lines by Western blotting. It could also significantly
      inhibit the in vitro adhesive, invasive, and migratory and in vivo metastatic
      abilities of gastric cancer cell lines SGC7901 and MKN45 by reducing urokinase
      type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 proteins
      and by increasing tissue inhibitor of matrix metalloproteinase (TIMP)-1 protein.
      Further studies showed that p75NTR could suppress the nuclear factor-kappaB (NF
      kappaB) signal. SN50, a specific inhibitor of NF-kappaB, which could inhibit in
      vitro invasive and migratory abilities of gastric cancer cells, reduced
      expression of uPA and MMP9 proteins and increased expression of TIMP1 protein.
      Taken together, p75NTR had the function of inhibiting the invasive and metastatic
      abilities of gastric cancer cells, which was mediated, at least partially, by
      down-regulation of uPA and MMP9 proteins and up-regulation of TIMP1 protein via
      the NF-kappaB signal transduction pathway. Our studies suggested that p75NTR may
      be used as a new potential therapeutic target in metastatic gastric cancer.

PMID- 17510310
TI  - Silencing of cyclooxygenase-2 inhibits metastasis and delays tumor onset of
      poorly differentiated metastatic breast cancer cells.
AB  - Cyclooxygenases (COX) are rate-limiting enzymes involved in the conversion of
      PLA(2)-mobilized arachidonic acid into prostaglandins and thromboxanes. COX-2 is
      a key mediator of inflammation during both physiologic and pathologic responses
      to endogenous stimuli and infectious agents. Its overexpression has been detected
      in different cancers, including that of the breast. Using RNA interference, we
      have reduced the expression of COX-2 in the highly malignant breast cancer cell
      line MDA-MB-231 below detectable levels in response to interleukin-1 beta or 12-O
      tetradecanoylphorbol-13-acetate treatment. Microarray analysis showed that COX-2
      silencing resulted in the loss of mRNA expression of several oncogenic markers,
      such as matrix metalloproteinase-1, chemokine (C-X-C motif) receptor 4, and
      interleukin-11, which have been correlated with poor disease outcome, and in the
      up-regulation of antimetastatic transcripts, such as thrombospondin-1 and Epstein
      Barr-Induced 3. Cells lacking COX-2 were less able to invade reconstituted
      extracellular matrix than parental cells in vitro. Consistent with these changes,
      loss of COX-2 resulted in the abolition or the significant delay of tumor onset
      when the cells were injected in the mammary fat pad of severe combined
      immunodeficient mice. Finally, silencing of COX-2 resulted in the inhibition of
      metastasis to the lungs of severe combined immunodeficient mice after intravenous
      injection. These data show that silencing of COX-2 abolishes the metastatic
      potential of MDA-MB-231 cells in vivo.

PMID- 17510311
TI  - Hu/Mu ProtIn oligonucleotide microarray: dual-species array for profiling
      protease and protease inhibitor gene expression in tumors and their
      microenvironment.
AB  - Proteolysis is a critical regulatory mechanism for a wide variety of physiologic
      and pathologic processes. To assist in the identification of proteases, their
      endogenous inhibitors, and proteins that interact with proteases or proteolytic
      pathways in biological tissues, a dual-species oligonucleotide microarray has
      been developed in conjunction with Affymetrix. The Hu/Mu ProtIn microarray
      contains 516 and 456 probe sets that survey human and mouse genes of interest
      (proteases, protease inhibitors, or interactors), respectively. To investigate
      the performance of the array, gene expression profiles were analyzed in pure
      mouse and human samples (reference RNA; normal and tumor cell lines/tissues) and
      orthotopically implanted xenografts of human A549 lung and MDA-MB-231 breast
      carcinomas. Relative gene expression and "present-call" P values were determined
      for each probe set using dChip and MAS5 software, respectively. Despite the high
      level of sequence identity of mouse and human protease/inhibitor orthologues and
      the theoretical potential for cross-hybridization of some of the probes, >95% of
      the "present calls" (P<0.01) resulted from same-species hybridizations (e.g.,
      human transcripts to human probe sets). To further assess the performance of the
      microarray, differential gene expression and false discovery rate analyses were
      carried out on human or mouse sample groups, and data processing methods to
      optimize performance of the mouse and human probe sets were identified. The Hu/Mu
      ProtIn microarray is a valuable discovery tool for the identification of
      components of human and murine proteolytic pathways in health and disease and has
      particular utility in the determination of cellular origins of proteases and
      protease inhibitors in xenograft models of human cancer.

PMID- 17510312
TI  - Assessment of methylation events during colorectal tumor progression by absolute
      quantitative analysis of methylated alleles.
AB  - To date, the epigenetic events involved in the progression of colorectal cancer
      are not well described. To study, in detail, methylation during colorectal cancer
      development in high-risk adenomas, we developed an assay combining in situ (on
      slide) sodium bisulfite modification (SBM) of paraffin-embedded archival tissue
      sections with absolute quantitative assessment of methylated alleles (AQAMA). We
      tested the performance of the assay to detect methylation level differences
      between paired pre-malignant and malignant colorectal cancer stages. AQAMA assays
      were used to measure methylation levels at MINT (methylated in tumor) loci MINT1,
      MINT2, MINT12, and MINT31. Assay performance was verified on cell line DNA and
      standard cDNA. On-slide SBM, allowing DNA methylation assessment of 1 to 2 mm(2)
      of paraffin-embedded archival tissue, was employed. Methylation levels of
      adenomatous and cancerous components within a single tissue section in 72
      colorectal cancer patients were analyzed. AQAMA was verified as accurately
      assessing CpG island methylation status in cell lines. The correlation between
      expected and measured cDNA methylation levels was high for all four MINT AQAMA
      assays (R >or= 0.966, P<0.001). Methylation levels at the four loci increased in
      11% and decreased in 36% of specimens comparing paired adenoma and cancer tissues
      (P<0.0001 by Kolmogorov-Smirnov test). Single-PCR AQAMA provided accurate
      methylation level measurement. Variable MINT locus methylation level changes
      occur during malignant progression of colorectal adenoma. Combining AQAMA with on
      slide SBM provides a sensitive assay that allows detailed histology-oriented
      analysis of DNA methylation levels and may give new, accurate insights into
      understanding development of epigenetic aberrancies in colorectal cancer
      progression.

PMID- 17510313
TI  - G alpha 12/13 basally regulates p53 through Mdm4 expression.
AB  - G alpha(12/13), which belongs to the G alpha(12) family, participates in the
      regulation of diverse physiologic processes. In view of the control of G
      alpha(12/13) in cell proliferation, this study investigated the role of G
      alpha(12/13) in the regulation of p53 and mdm4. Immunoblotting and
      immunocytochemistry revealed that p53 was expressed in control embryonic
      fibroblasts and was largely localized in the nuclei. G alpha(12) deficiency
      decreased p53 levels and its DNA binding activity, accompanying p21 repression
      with Bcl(2) induction, whereas G alpha(13) deficiency exerted weak effects. G
      alpha(12) or G alpha(13) deficiency did not change p53 mRNA expression. ERK1/2 or
      Akt was not responsible for p53 repression due to G alpha(12) deficiency. Mdm4, a
      p53-stabilizing protein, was repressed by G alpha(12) deficiency and to a lesser
      extent by G alpha(13) deficiency, whereas mdm2, PTEN, beta-catenin, ATM, and Chk2
      were unaffected. p53 accumulation by proteasomal inhibition during G alpha(12)
      deficiency suggested the role of G alpha(12) in p53 stabilization. Constitutively
      active G alpha(12) (G alpha(12)QL) or G alpha(13) (G alpha(13)QL) promoted p53
      accumulation with mdm4 induction in MCF10A cells. p53 accumulation by mdm4
      overexpression, but no mdm4 induction by p53 overexpression, and small
      interfering RNA knockdown verified the regulatory role of mdm4 for p53 downstream
      of G alpha(12/13). In control or G alpha(12)/G alpha(13)-deficient cells,
      genotoxic stress led to p53 accumulation. At concentrations increasing the flow
      cytometric pre-G(1) phase, doxorubicin or etoposide treatment caused serine
      phosphorylations in G alpha(12)-/- or G alpha(12/13)-/- cells, but did not induce
      mdm4. G alpha(12/13)QL transfection failed to phosphorylate p53 at serines. Our
      results indicate that G alpha(12/13) regulate basal p53 levels via mdm4, which
      constitutes a cell signaling pathway distinct from p53 phosphorylations elicited
      by genotoxic stress.

PMID- 17510314
TI  - Src induces urokinase receptor gene expression and invasion/intravasation via
      activator protein-1/p-c-Jun in colorectal cancer.
AB  - The urokinase receptor [urokinase plasminogen activator receptor (u-PAR)]
      promotes invasion and metastasis and is associated with poor patient survival.
      Recently, it was shown that Src induces u-PAR gene expression via Sp1 bound to
      the u-PAR promoter region -152/-135. However, u-PAR is regulated by diverse
      promoter motifs, among them being an essential activator protein-1 (AP-1) motif
      at -190/-171. Moreover, an in vivo relevance of Src-induced transcriptional
      regulators of u-PAR-mediated invasion, in particular intravasation, and a
      relevance in resected patient tumors have not sufficiently been shown. The
      present study was conducted (a) to investigate if, in particular, AP-1-related
      transcriptional mediators are required for Src-induced u-PAR-gene expression, (b)
      to show in vivo relevance of AP-1-mediated Src-induced u-PAR gene expression for
      invasion/intravasation and for resected tissues from colorectal cancer patients.
      Src stimulation of the u-PAR promoter deleted for AP-1 region -190/-171 was
      reduced as compared with the wild-type promoter in cultured colon cancer cells.
      In gelshifts/chromatin immunoprecipitation, Src-transfected SW480 cells showed an
      increase of phospho-c-Jun, in addition to JunD and Fra-1, bound to region -190/
      171. Src-transfected cells showed a significant increase in c-Jun phosphorylated
      at Ser(73) and also Ser(63), which was paralleled by increased phospho-c-jun
      NH(2)-kinase. Significant decreases of invasion/in vivo intravasation
      (chorionallantoic membrane model) were observed in Src-overexpressing cells
      treated with Src inhibitors, u-PAR-small interfering RNA, and dominant negative c
      Jun (TAM67). In resected tissues of 20 colorectal cancer patients, a significant
      correlation between Src activity, AP-1 complexes bound to u-PAR region -190/-171,
      and advanced pN stage were observed. These data suggest that Src-induced u-PAR
      gene expression and invasion/intravasation in vivo is also mediated via AP-1
      region -190/-171, especially bound with c-Jun phosphorylated at Ser(73/63), and
      that this pathway is biologically relevant for colorectal cancer patients,
      suggesting therapeutic potential.

PMID- 17510315
TI  - TAT-RasGAP317-326 requires p53 and PUMA to sensitize tumor cells to genotoxins.
AB  - Although chemotherapy has revolutionized cancer treatment, the associated side
      effects induced by lack of specificity to tumor cells remain a challenging
      problem. We have previously shown that TAT-RasGAP(317-326),a cell-permeable
      peptide derived from RasGAP, specifically sensitizes cancer cells to the action
      of genotoxins. The underlying mechanisms of this sensitization were not defined
      however. Here, we report that TAT-RasGAP(317-326) requires p53, but not the Ras
      effectors Akt and extracellular signal-regulated kinase, to mediate its tumor
      sensitization abilities. The TAT-RasGAP(317-326) peptide, although not modulating
      the transcriptional activity of p53 or its phosphorylation and acetylation
      status, nevertheless requires a functional p53 cellular status to increase the
      sensitivity of tumor cells to genotoxins. Genes regulated by p53 encode
      proapoptotic proteins, such as PUMA, and cell cycle control proteins, such as
      p21. The ability of TAT-RasGAP(317-326) to sensitize cancer cells was found to
      require PUMA but not p21. TAT-RasGAP(317-326) did not affect PUMA levels,
      however, but increased genotoxin-induced mitochondrial depolarization and caspase
      3 activation. These results indicate that TAT-RasGAP(317-326) sensitizes tumor
      cells by activating signals that intersect with the p53 pathway downstream of, or
      at the level of, proapoptotic p53 target gene products to increase the activation
      of the mitochondrial death pathway.

PMID- 17510316
TI  - Down-regulation of Sprouty2 in non-small cell lung cancer contributes to tumor
      malignancy via extracellular signal-regulated kinase pathway-dependent and 
      independent mechanisms.
AB  - Sprouty (Spry) proteins function as inhibitors of receptor tyrosine kinase
      signaling mainly by interfering with the Ras/Raf/mitogen-activated protein kinase
      cascade, a pathway known to be frequently deregulated in human non-small cell
      lung cancer (NSCLC). In this study, we show a consistently lowered Spry2
      expression in NSCLC when compared with the corresponding normal lung epithelium.
      Based on these findings, we investigated the influence of Spry2 expression on the
      malignant phenotype of NSCLC cells. Ectopic expression of Spry2 antagonized
      mitogen-activated protein kinase activity and inhibited cell migration in cell
      lines homozygous for K-Ras wild type, whereas in NSCLC cells expressing mutated K
      Ras, Spry2 failed to diminish extracellular signal-regulated kinase (ERK)
      phosphorylation. Nonetheless, Spry2 significantly reduced cell proliferation in
      all investigated cell lines and blocked tumor formation in mice. Accordingly, a
      Spry2 mutant unable to inhibit ERK phosphorylation reduced cell proliferation
      significantly but less pronounced compared with the wild-type protein. Therefore,
      we conclude that Spry2 interferes with ERK phosphorylation and another yet
      unidentified pathway. Our results suggest that Spry2 plays a role as tumor
      suppressor in NSCLC by antagonizing receptor tyrosine kinase-induced signaling at
      different levels, indicating feasibility for the usage of Spry in targeted gene
      therapy of NSCLC.

PMID- 17510318
TI  - Cyclic Arg-Gly-Asp peptide-labeled liposomes for targeting drug therapy of
      hepatic fibrosis in rats.
AB  - Targeting hepatic stellate cells (HSCs) has been challenging due to the lack of
      specific receptors or motifs on the cells. The aim of the present study was to
      develop a HSC-specific system for improving drug delivery to HSCs. The affinity
      of a cyclic peptide containing Arg-Gly-Asp (cRGD) to collagen type VI receptor on
      HSCs was examined in both in vitro and in vivo experiments. Sterically stable
      liposomes (SSLs) were modified with this peptide to yield a new carrier, cRGD
      SSL. The targeting efficiency of this carrier in delivering interferon (IFN)
      alpha1b was investigated in a rat model of liver fibrosis induced by bile duct
      ligation (BDL). When incubating HSCs or hepatocytes with cyclic RGD peptide, the
      peptide was bound preferentially to activated HSCs. Biodistribution study showed
      that the accumulation of cRGD peptide-labeled liposomes in HSCs isolated from BDL
      rats was 10-fold more than unlabeled SSLs. BDL rats receiving injections of IFN
      alpha1b entrapped in cRGD-SSL exhibited significantly reduced extent of liver
      fibrosis compared with BDL control rats or BDL rats treated with IFN-alpha1b
      entrapped in SSLs. Thus, cRGD-SSL is an efficient drug carrier, which selectively
      targets activated HSCs and improves drug therapy for liver fibrosis to a
      significant extent. This liposomal formulation represents a new means of
      targeting drug carrier for the treatment of liver fibrosis, and it may have
      potential clinical applications.

PMID- 17510319
TI  - Benzodiazepine withdrawal-induced glutamatergic plasticity involves up-regulation
      of GluR1-containing alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      receptors in Hippocampal CA1 neurons.
AB  - Modification of glutamatergic synaptic function, a mechanism central to neuronal
      plasticity, may also mediate long-term drug effects, including dependence and
      addiction. Benzodiazepine withdrawal results in increased glutamatergic strength,
      but whether alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      receptors (AMPARs) are functionally and structurally remodeled during
      benzodiazepine withdrawal is uncertain. Whole-cell recordings of rat hippocampal
      CA1 neurons, either acutely dissociated or in hippocampal slices, revealed that
      AMPAR function was enhanced up to 50% during flurazepam (FZP) withdrawal, without
      changes in whole-cell channel kinetic properties. Agonist-elicited AMPA currents
      showed a negative shift in rectification in the presence of spermine, suggesting
      augmented membrane incorporation of glutamate receptor (GluR) 2-lacking AMPARs.
      As GluR1-containing AMPARs are critical for activity-dependent alterations in
      excitatory strength, we sought to determine whether changes in GluR1 subunit
      distribution in CA1 neurons occurred during benzodiazepine withdrawal. Confocal
      image analysis revealed that FZP withdrawal promoted GluR1 subunit incorporation
      into somatic and proximal dendritic membranes of CA1 neurons without GluR2
      subunit alterations. Findings of immunoblot studies were consistent with
      immunofluorescent studies indicating increased GluR1, but not GluR2, subunit
      protein levels in cytosolic, crude membrane and postsynaptic density-enriched
      fractions from CA1 minislices. As with long-term potentiation (LTP), the FZP
      withdrawal-induced GluR1 incorporation into CA1 neuron membranes may require the
      GluR1-trafficking protein, synapse-associated protein 97, which was also elevated
      in membrane-associated fractions. Together, our findings provide evidence that
      during FZP withdrawal, increased membrane incorporation of GluR1-containing
      AMPARs and associated up-regulation of AMPAR functions in hippocampal CA1
      pyramidal neurons share fundamental similarities with the mechanisms underlying
      LTP. This implies that glutamatergic neuronal remodeling observed in LTP also
      subserves physiological adaptations to drug withdrawal.

PMID- 17510320
TI  - Adenoviral vectors persist in vivo and maintain activated CD8+ T cells:
      implications for their use as vaccines.
AB  - CD8(+) T cell-numbers rapidly expand and then contract after exposure to their
      cognate antigen. Here we show that the sustained frequencies of transgene product
      specific CD8(+) T cells elicited by replication-defective adenovirus vectors are
      linked to persistence of low levels of transcriptionally active adenovirus vector
      genomes at the site of inoculation, in liver, and lymphatic tissues. Continuously
      produced small amounts of antigen maintain fully active effector CD8(+) T cells,
      while also allowing for their differentiation into central memory cells. The long
      term persistence of adenoviral vectors may be highly advantageous for their use
      as vaccines against pathogens for which T-cell-mediated protection requires both
      fully activated T cells for immediate control of virus-infected cells and central
      memory CD8(+) T cells that, because of their higher proliferative capacity, may
      be suited best to eliminate cells infected by pathogens that escaped the initial
      wave of effector T cells.

PMID- 17510322
TI  - The SOCS box of suppressor of cytokine signaling-3 contributes to the control of
      G-CSF responsiveness in vivo.
AB  - Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of granulocyte
      colony stimulating factor (G-CSF) signaling in vivo. SOCS proteins regulate
      cytokine signaling by binding, via their SH2 domains, to activated cytokine
      receptors or their associated Janus kinases. In addition, they bind to the
      elongin B/C ubiquitin ligase complex via the SOCS box. To ascertain the
      contribution of the SOCS box of SOCS3 to in vivo regulation of G-CSF signaling,
      we generated mice expressing a truncated SOCS3 protein lacking the C-terminal
      SOCS box (SOCS3(Delta SB/Delta SB)). SOCS3(Delta SB/Delta SB) mice were viable,
      had normal steady-state hematopoiesis, and did not develop inflammatory disease.
      Despite the mild phenotype, STAT3 activation in response to G-CSF signaling was
      prolonged in SOCS3(Delta SB/Delta SB) bone marrow. SOCS3(Delta SB/Delta SB) bone
      marrow contained increased numbers of colony-forming cells responsive to G-CSF
      and IL-6. Treatment of the mice with pharmacologic doses of G-CSF, which mimics
      emergency granulopoiesis and therapeutic use of G-CSF, revealed that SOCS3(Delta
      SB/Delta SB) mice were hyperresponsive to G-CSF. Compared with wild-type mice,
      SOCS3(Delta SB/Delta SB) mice developed a more florid arthritis when tested using
      an acute disease model. Overall, the results establish a role for the SOCS box of
      SOCS3 in the in vivo regulation of G-CSF signaling and the response to
      inflammatory stimuli.

PMID- 17510321
TI  - Targeting MEK induces myeloma-cell cytotoxicity and inhibits osteoclastogenesis.
AB  - Activation of the extracellular signal-regulated kinase1/2 (ERK1/2) signaling
      cascade mediates human multiple myeloma (MM) growth and survival triggered by
      cytokines and adhesion to bone marrow stromal cells (BMSCs). Here, we examined
      the effect of AZD6244 (ARRY-142886), a novel and specific MEK1/2 inhibitor, on
      human MM cell growth in the bone marrow (BM) milieu. AZD6244 blocks constitutive
      and cytokine-stimulated ERK1/2 phosphorylation and inhibits proliferation and
      survival of human MM cell lines and patient MM cells, regardless of sensitivity
      to conventional chemotherapy. Importantly, AZD6244 (200 nM) induces apoptosis in
      patient MM cells, even in the presence of exogenous interleukin-6 or BMSCs
      associated with triggering of caspase 3 activity. AZD6244 sensitizes MM cells to
      both conventional (dexamethasone) and novel (perifosine, lenalidomide, and
      bortezomib) therapies. AZD6244 down-regulates the expression/secretion of
      osteoclast (OC)-activating factors from MM cells and inhibits in vitro
      differentiation of MM patient PBMCs to OCs induced by ligand for receptor
      activator of NF-kappaB (RANKL) and macrophage-colony stimulating factor (M-CSF).
      Finally, AZD6244 inhibits tumor growth and prolongs survival in vivo in a human
      plasmacytoma xenograft model. Taken together, these results show that AZD6244
      targets both MM cells and OCs in the BM microenvironment, providing the
      preclinical framework for clinical trials to improve patient outcome in MM.

PMID- 17510323
TI  - Bone marrow CD8 cells down-modulate membrane IL-7Ralpha expression and exhibit
      increased STAT-5 and p38 MAPK phosphorylation in the organ environment.
AB  - By comparing mature CD8-cell turnover in different organs, we previously
      demonstrated that CD8 cells proliferate predominantly in the bone marrow (BM). To
      investigate the mechanisms underlying such increased turnover, we compared BM,
      lymph nodes, and spleen CD8 cells from untreated C57BL/6 mice regarding in vivo
      proliferation within the organ; in vitro response to interleukin-7 (IL-7), IL-15,
      IL-21; ex vivo expression of membrane CD127 (IL-7Ralpha), intracellular Bcl-2,
      phospho-STAT-5 (signal transducer and activator of transcription 5), phospho-p38
      mitogen activated protein kinase (MAPK); and in vivo proliferation on adoptive
      transfer. In the BM, the proliferation rate was increased for either total CD8
      cells or individual CD44 and CD122 subsets. In contrast, purified CD8(+) cells
      from the BM did not show an enhanced in vitro proliferative response to IL-7, IL
      15, and IL-21 compared with corresponding spleen cells. After transfer and
      polyinosinic-polycytidylic acid (polyI:C) treatment, both spleen-derived and BM
      derived CD8 cells from congenic donors proliferated approximately twice more in
      the recipient BM than in spleen and lymph nodes. Our results suggest that BM CD8
      cells are not committed to self-renewal, but rather are stimulated in the organ.
      Molecular events constantly induced in the CD8 cells within the BM of untreated
      mice include increase of both phosphorylated STAT-5 and phosphorylated p38
      intracellular levels, and the reduction of CD127 membrane expression.

PMID- 17510325
TI  - RNA maps reveal new RNA classes and a possible function for pervasive
      transcription.
AB  - Significant fractions of eukaryotic genomes give rise to RNA, much of which is
      unannotated and has reduced protein-coding potential. The genomic origins and the
      associations of human nuclear and cytosolic polyadenylated RNAs longer than 200
      nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this
      genome-wide study. Subcellular addresses for nucleotides present in detected RNAs
      were assigned, and their potential processing into short RNAs was investigated.
      Taken together, these observations suggest a novel role for some unannotated RNAs
      as primary transcripts for the production of short RNAs. Three potentially
      functional classes of RNAs have been identified, two of which are syntenically
      conserved and correlate with the expression state of protein-coding genes. These
      data support a highly interleaved organization of the human transcriptome.

PMID- 17510326
TI  - Locating the two black holes in NGC 6240.
AB  - Mergers play an important role in galaxy evolution and are key to understanding
      the correlation between central-black hole mass and host-galaxy properties. We
      used the new technology of adaptive optics at the Keck II telescope to observe
      NGC 6240, a merger between two disk galaxies. Our high-resolution near-infrared
      images, combined with radio and x-ray positions, revealed the location and
      environment of two central supermassive black holes. Each is at the center of a
      rotating stellar disk, surrounded by a cloud of young star clusters. The
      brightest of these young clusters lie in the plane of each disk, but surprisingly
      are seen only on the disks' receding side.

PMID- 17510324
TI  - Genome sequence of Aedes aegypti, a major arbovirus vector.
AB  - We present a draft sequence of the genome of Aedes aegypti, the primary vector
      for yellow fever and dengue fever, which at approximately 1376 million base pairs
      is about 5 times the size of the genome of the malaria vector Anopheles gambiae.
      Nearly 50% of the Ae. aegypti genome consists of transposable elements. These
      contribute to a factor of approximately 4 to 6 increase in average gene length
      and in sizes of intergenic regions relative to An. gambiae and Drosophila
      melanogaster. Nonetheless, chromosomal synteny is generally maintained among all
      three insects, although conservation of orthologous gene order is higher (by a
      factor of approximately 2) between the mosquito species than between either of
      them and the fruit fly. An increase in genes encoding odorant binding, cytochrome
      P450, and cuticle domains relative to An. gambiae suggests that members of these
      protein families underpin some of the biological differences between the two
      mosquito species.

PMID- 17510327
TI  - Saturation of the southern ocean CO2 sink due to recent climate change.
AB  - Based on observed atmospheric carbon dioxide (CO2) concentration and an inverse
      method, we estimate that the Southern Ocean sink of CO2 has weakened between 1981
      and 2004 by 0.08 petagrams of carbon per year per decade relative to the trend
      expected from the large increase in atmospheric CO2. We attribute this weakening
      to the observed increase in Southern Ocean winds resulting from human activities,
      which is projected to continue in the future. Consequences include a reduction of
      the efficiency of the Southern Ocean sink of CO2 in the short term (about 25
      years) and possibly a higher level of stabilization of atmospheric CO2 on a
      multicentury time scale.

PMID- 17510329
TI  - Research integrity. Sonofusion back on the firing line as misconduct probe
      reopens.

PMID- 17510328
TI  - Behavioral science comes of age.

PMID- 17510330
TI  - U.K. research. Blair departs after a decade of strong support for science.

PMID- 17510331
TI  - Life sciences research. Massachusetts proposes $1 billion plan.

PMID- 17510332
TI  - Ancient DNA. No sex please, we're Neandertals.

PMID- 17510333
TI  - Australian science. Universities are big winners in election-year budget.

PMID- 17510334
TI  - Biomedical research. Temporary cuts hit labs at child health institute.

PMID- 17510335
TI  - Ecology. Savannah River Lab to close after DOE cuts its funding.

PMID- 17510336
TI  - Entomology. The case of the empty hives.

PMID- 17510337
TI  - Susan Dudley profile: New regulatory czar says rules 'should make people better
      off'.

PMID- 17510338
TI  - Susan Dudley profile. Decision on lead emissions weighs heavily on EPA.

PMID- 17510339
TI  - Wildlife conservation. Giant panda numbers are surging--or are they?

PMID- 17510340
TI  - Psychiatric research. Putting the brakes on psychosis.

PMID- 17510341
TI  - Society for American Archaeology meeting. Portals to the supernatural world
      uncovered in Mayan tomb.

PMID- 17510343
TI  - Society for American Archaeology meeting. Snapshots from the meeting.

PMID- 17510342
TI  - Society for American Archaeology meeting. Climate spurred later Indus decline.

PMID- 17510344
TI  - When the oil supply runs out.

PMID- 17510345
TI  - Testosterone and male fertility in red deer.

PMID- 17510346
TI  - Further notes on quasi-crystal tilings.

PMID- 17510347
TI  - Comment on "A centrosome-independent role for gamma-TuRC proteins in the spindle
      assembly checkpoint".
AB  - Muller et al. (Reports, 27 October 2006, p. 654) showed that inhibition of the
      gamma-tubulin ring complex (gamma-TuRC) activates the spindle assembly checkpoint
      (SAC), which led them to suggest that gamma-TuRC proteins play molecular roles in
      SAC activation. Because gamma-TuRC inhibition leads to pleiotropic spindle
      defects, which are well known to activate kinetochore-derived checkpoint
      signaling, we believe that this conclusion is premature.

PMID- 17510348
TI  - Comment on "A centrosome-independent role for gamma-TuRC proteins in the spindle
      assembly checkpoint".
AB  - Muller et al. (Reports, 27 October 2006, p. 654) proposed a role for microtubule
      nucleation in mitotic checkpoint signaling. However, their observations of
      spindle defects and mitotic delay after depletion of gamma-tubulin ring complex
      (gamma-TuRC) components are fully consistent with activation of the established
      pathway of checkpoint signaling in response to incomplete or unstable
      interactions between kinetochores of mitotic chromosomes and spindle
      microtubules.

PMID- 17510349
TI  - Ecology. Danger of deep-sea mining.

PMID- 17510351
TI  - Physics. Condensates made of light.

PMID- 17510350
TI  - Cancer. Converging on beta-catenin in Wilms tumor.

PMID- 17510352
TI  - Developmental biology. A decade of cloning mystique.

PMID- 17510353
TI  - Ocean science. Highly active eddies.

PMID- 17510354
TI  - Planetary science. The shifting sands of asteroids.

PMID- 17510355
TI  - Retrospective: Francis Clark Howell (1925-2007).

PMID- 17510356
TI  - Childhood origins of adult resistance to science.
AB  - Resistance to certain scientific ideas derives in large part from assumptions and
      biases that can be demonstrated experimentally in young children and that may
      persist into adulthood. In particular, both adults and children resist acquiring
      scientific information that clashes with common-sense intuitions about the
      physical and psychological domains. Additionally, when learning information from
      other people, both adults and children are sensitive to the trustworthiness of
      the source of that information. Resistance to science, then, is particularly
      exaggerated in societies where nonscientific ideologies have the advantages of
      being both grounded in common sense and transmitted by trustworthy sources.

PMID- 17510357
TI  - The new synthesis in moral psychology.
AB  - People are selfish, yet morally motivated. Morality is universal, yet culturally
      variable. Such apparent contradictions are dissolving as research from many
      disciplines converges on a few shared principles, including the importance of
      moral intuitions, the socially functional (rather than truth-seeking) nature of
      moral thinking, and the coevolution of moral minds with cultural practices and
      institutions that create diverse moral communities. I propose a fourth principle
      to guide future research: Morality is about more than harm and fairness. More
      research is needed on the collective and religious parts of the moral domain,
      such as loyalty, authority, and spiritual purity.

PMID- 17510358
TI  - Embodying emotion.
AB  - Recent theories of embodied cognition suggest new ways to look at how we process
      emotional information. The theories suggest that perceiving and thinking about
      emotion involve perceptual, somatovisceral, and motoric reexperiencing
      (collectively referred to as "embodiment") of the relevant emotion in one's self.
      The embodiment of emotion, when induced in human participants by manipulations of
      facial expression and posture in the laboratory, causally affects how emotional
      information is processed. Congruence between the recipient's bodily expression of
      emotion and the sender's emotional tone of language, for instance, facilitates
      comprehension of the communication, whereas incongruence can impair
      comprehension. Taken all together, recent findings provide a scientific account
      of the familiar contention that "when you're smiling, the whole world smiles with
      you."

PMID- 17510359
TI  - Sound production in the clownfish Amphiprion clarkii.
AB  - Although clownfish sounds were recorded as early as 1930, the mechanism of sound
      production has remained obscure. Yet, clownfish are prolific "singers" that
      produce a wide variety of sounds, described as "chirps" and "pops" in both
      reproductive and agonistic behavioral contexts. Here, we describe the sonic
      mechanism of the clownfish Amphiprion clarkii.

PMID- 17510360
TI  - Bose-Einstein condensation of microcavity polaritons in a trap.
AB  - We have created polaritons in a harmonic potential trap analogous to atoms in
      optical traps. The trap can be loaded by creating polaritons 50 micrometers from
      its center that are allowed to drift into the trap. When the density of
      polaritons exceeds a critical threshold, we observe a number of signatures of
      Bose-Einstein condensation: spectral and spatial narrowing, a peak at zero
      momentum in the momentum distribution, first-order coherence, and spontaneous
      linear polarization of the light emission. The polaritons, which are eigenstates
      of the light-matter system in a microcavity, remain in the strong coupling regime
      while going through this dynamical phase transition.

PMID- 17510361
TI  - Molecular basis of the shish-kebab morphology in polymer crystallization.
AB  - In the rich and long-standing literature on the flow-induced formation of
      oriented precursors to polymer crystallization, it is often asserted that the
      longest, most extended chains are the dominant molecular species in the "shish"
      of the "shish-kebab" formation. We performed a critical examination of this
      widely held view, using deuterium labeling to distinguish different chain lengths
      within an overall distribution. Small-angle neutron-scattering patterns of the
      differently labeled materials showed that long chains are not overrepresented in
      the shish relative to their concentration in the material as a whole. We observed
      that the longest chains play a catalytic role, recruiting other chains adjacent
      to them into formation of the shish.

PMID- 17510362
TI  - Mesoscale eddies drive increased silica export in the subtropical Pacific Ocean.
AB  - Mesoscale eddies may play a critical role in ocean biogeochemistry by increasing
      nutrient supply, primary production, and efficiency of the biological pump, that
      is, the ratio of carbon export to primary production in otherwise nutrient
      deficient waters. We examined a diatom bloom within a cold-core cyclonic eddy off
      Hawaii. Eddy primary production, community biomass, and size composition were
      markedly enhanced but had little effect on the carbon export ratio. Instead, the
      system functioned as a selective silica pump. Strong trophic coupling and
      inefficient organic export may be general characteristics of community
      perturbation responses in the warm waters of the Pacific Ocean.

PMID- 17510363
TI  - Eddy/wind interactions stimulate extraordinary mid-ocean plankton blooms.
AB  - Episodic eddy-driven upwelling may supply a significant fraction of the nutrients
      required to sustain primary productivity of the subtropical ocean. New
      observations in the northwest Atlantic reveal that, although plankton blooms
      occur in both cyclones and mode-water eddies, the biological responses differ.
      Mode-water eddies can generate extraordinary diatom biomass and primary
      production at depth, relative to the time series near Bermuda. These blooms are
      sustained by eddy/wind interactions, which amplify the eddy-induced upwelling. In
      contrast, eddy/wind interactions dampen eddy-induced upwelling in cyclones.
      Carbon export inferred from oxygen anomalies in eddy cores is one to three times
      as much as annual new production for the region.

PMID- 17510364
TI  - Stress control of deep rift intrusion at Mauna Loa volcano, Hawaii.
AB  - Mauna Loa volcano, Hawaii, deforms by a combination of shallow dike intrusions in
      the rift zones and earthquakes along the base of the volcano, but it is not known
      how the spreading is accommodated in the lower part of the volcanic edifice. We
      present evidence from interferometric synthetic aperture radar data for secular
      inflation of a dike-like magma body at intermediate depth in the southwest rift
      zone during 2002 to 2005. Magma accumulation occurred in a section of the rift
      zone that was unclamped by previous dikes and earthquakes, suggesting that stress
      transfer plays an important role in controlling subsurface magma accumulation.

PMID- 17510365
TI  - Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling.
AB  - Aberrant WNT signal transduction is involved in many diseases. In colorectal
      cancer and melanoma, mutational disruption of proteins involved in the
      degradation of beta-catenin, the key effector of the WNT signaling pathway,
      results in stabilization of beta-catenin and, in turn, activation of
      transcription. We have used tandem-affinity protein purification and mass
      spectrometry to define the protein interaction network of the beta-catenin
      destruction complex. This assay revealed that WTX, a protein encoded by a gene
      mutated in Wilms tumors, forms a complex with beta-catenin, AXIN1, beta-TrCP2
      (beta-transducin repeat-containing protein 2), and APC (adenomatous polyposis
      coli). Functional analyses in cultured cells, Xenopus, and zebrafish demonstrate
      that WTX promotes beta-catenin ubiquitination and degradation, which antagonize
      WNT/beta-catenin signaling. These data provide a possible mechanistic explanation
      for the tumor suppressor activity of WTX.

PMID- 17510366
TI  - Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed
      chromatin.
AB  - Nucleosomes must be deacetylated behind elongating RNA polymerase II to prevent
      cryptic initiation of transcription within the coding region. RNA polymerase II
      signals for deacetylation through the methylation of histone H3 lysine 36
      (H3K36), which provides the recruitment signal for the Rpd3S histone deacetylase
      complex (HDAC). The recognition of methyl H3K36 by Rpd3S requires the
      chromodomain of its Eaf3 subunit. Paradoxically, Eaf3 is also a subunit of the
      NuA4 acetyltransferase complex, yet NuA4 does not recognize methyl H3K36
      nucleosomes. In Saccharomyces cerevisiae, we found that methyl H3K36 nucleosome
      recognition by Rpd3S also requires the plant homeobox domain (PHD) of its Rco1
      subunit. Thus, the coupled chromo and PHD domains of Rpd3S specify recognition of
      the methyl H3K36 mark, demonstrating the first combinatorial domain requirement
      within a protein complex to read a specific histone code.

PMID- 17510368
TI  - Careers in behavioral science. Behavioral scientists get off the trail.

PMID- 17510367
TI  - Conformational switching in the fungal light sensor Vivid.
AB  - The Neurospora crassa photoreceptor Vivid tunes blue-light responses and
      modulates gating of the circadian clock. Crystal structures of dark-state and
      light-state Vivid reveal a light, oxygen, or voltage Per-Arnt-Sim domain with an
      unusual N-terminal cap region and a loop insertion that accommodates the flavin
      cofactor. Photoinduced formation of a cystein-flavin adduct drives flavin
      protonation to induce an N-terminal conformational change. A cysteine-to-serine
      substitution remote from the flavin adenine dinucleotide binding site decouples
      conformational switching from the flavin photocycle and prevents Vivid from
      sending signals in Neurospora. Key elements of this activation mechanism are
      conserved by other photosensors such as White Collar-1, ZEITLUPE, ENVOY, and
      flavin-binding, kelch repeat, F-BOX 1 (FKF1).

PMID- 17510369
TI  - Careers in behavioral science. Neuromarketing careers.

PMID- 17510370
TI  - Careers in behavioral science. Public opinion research: measuring happiness.

PMID- 17510371
TI  - Optimized preservation of CNS morphology for the identification of glycogen in
      the Pompe mouse model.
AB  - Pompe disease (glycogenosis type II) is a rare lysosomal disorder caused by a
      mutational deficiency of acid alpha-glucosidase (GAA). This deficiency leads to
      glycogen accumulation in multiple tissues: heart, skeletal muscles, and the
      central nervous system. A knockout mouse model mimicking the human condition has
      been used for histological evaluation. Currently, the best method for preserving
      glycogen in Pompe samples uses epon-araldite resin. Although the preservation by
      this method is excellent, the size of the tissue is limited to 1 mm(3). To
      accurately evaluate brain pathology in the Pompe mouse model, a modified glycol
      methacrylate (JB-4 Plus) method was developed. This approach allowed the
      production of larger tissue sections encompassing an entire mouse hemisphere (8 x
      15 mm) while also providing a high level of morphological detail and preservation
      of glycogen. Application of the JB-4 Plus method is appropriate when a high level
      of cellular detail is desired. A modified paraffin method was also developed for
      use when rapid processing of multiple samples is a priority. Traditional paraffin
      processing results in glycogen loss. The modified paraffin method with periodic
      acid postfixation resulted in improved tissue morphology and glycogen
      preservation. Both techniques provide accurate anatomic evaluation of the
      glycogen distribution in Pompe mouse brain.

PMID- 17510372
TI  - Association of cortactin and fascin-1 expression in gastric adenocarcinoma:
      correlation with clinicopathological parameters.
AB  - Cortactin and fascin-1 are important factors in tumor progression. We tested the
      hypothesis that cortactin and fascin-1 expression correlates with
      clinicopathological parameters of gastric adenocarcinoma. Immunohistochemical
      analysis of cortactin and fascin-1 was done using tissue microarrays of 100
      surgical specimens, including 20 well-differentiated, 20 moderately
      differentiated, and 60 poorly differentiated gastric adenocarcinomas. Among the
      20 well-differentiated gastric adenocarcinomas, 15 cases (75%) showed negative or
      weak staining (1+); 5 cases (25%) had moderate (2+) or strong (3+) cortactin
      expression. Among the 60 poorly differentiated gastric adenocarcinomas, more than
      three-quarters of the cases (76.7%) had moderate or strong cortactin expression;
      14 cases (23.3%) had weak staining. Of 20 well-differentiated gastric
      adenocarcinoma cases, 14 (70%) showed negative or weak staining of fascin-1,
      whereas nearly one-third (30%) had moderate or strong expression. Among the 60
      poorly differentiated gastric adenocarcinomas, 32 (53.3%) exhibited moderate or
      strong fascin-1 expression; fewer than half of the cases showed negative or weak
      staining. Higher intensity of cortactin and fascin-1 staining correlated directly
      with more-advanced cancer stages (TNM) and inversely with survival rates. Our
      findings suggest the possibility that pharmacological inhibitors of cortactin and
      fascin-1 activity may slow down tumor progression and prolong survival time in
      patients with gastric adenocarcinomas.

PMID- 17510373
TI  - A comparative analysis of novel fluorescent proteins as reporters for gene
      transfer studies.
AB  - We evaluated novel fluorescent proteins (FPs) as reporters for gene transfer in
      animals and cells with the aim to develop more-sensitive assays for vector
      development and the optimization of gene transfer strategies in gene therapy.
      Adeno-associated virus serotype 5 vectors carrying an expression cassette with a
      chicken beta-actin promoter encoding the green FPs ZsGreen1, AcGFP1, hMGFP (with
      and without intron), and EGFP and the red FPs DsRed2 and TurboRFP were
      administered to mice at identical doses for each organ to target liver, lung, and
      muscle. Despite the fact that all FPs were expressed from an identical vector
      backbone, the observed number of fluorescent cells and fluorescence intensities
      varied between, but was consistent within, each combination of a specific protein
      and organ. The highest number of fluorescent cells was observed in liver with
      EGFP and in lung with ZsGreen1 and EGFP. In muscle, AcGFP1 and ZsGreen1 produced
      the most-intense fluorescence in fibers. In contrast, in culture cells, ZsGreen1
      showed substantially stronger fluorescence than all other proteins. Our data
      demonstrate that each FP has tissue-specific expression profiles that need to be
      taken into consideration when comparing the performance of vectors in different
      organs.

PMID- 17510374
TI  - Characterization of the column and autocellular junctions that define the
      vasculature of gill lamellae.
AB  - Novel adhesion junctions have been characterized that are formed at the interface
      between pillar cells and collagen columns, both of which are essential
      constituents of the gill lamellae in fish. We termed these junctions the "column
      junction" and "autocellular junction" and determined their molecular compositions
      by immunofluorescence microscopy using pufferfish. We visualized collagen columns
      by concanavalin A staining and found that the components of integrin-mediated
      cell-matrix adhesion, such as talin, vinculin, paxillin, and fibronectin, were
      concentrated on plasma membranes surrounding collagen columns (column membranes).
      This connection is analogous to the focal adhesion of cultured mammalian cells,
      dense plaque of smooth muscle cells, and myotendinous junction of skeletal muscle
      cells. We named this connection the "column junction." In the cytoplasm near the
      column, actin fibers, actinin, and a phosphorylated myosin light chain of 20 kDa
      are densely located, suggesting the contractile nature of pillar cells. The
      membrane infoldings surrounding the collagen columns were found to be connected
      by the autocellular junction, whose components are highly tyrosine-phosphorylated
      and contain the tight junction protein ZO-1. This study represents the first
      molecular characterization and fluorescence visualization of the column and
      autocellular junctions involved in both maintaining structural integrity and the
      hemodynamics of the branchial lamellae.

PMID- 17510375
TI  - Distribution of neuronal apoptosis inhibitory protein in human tissues.
AB  - The neuronal apoptosis inhibitory protein (NAIP) gene, also known as the
      baculovirus inhibitor of apoptosis repeat-containing protein 1 (BIRC1) gene, is a
      member of the inhibitors of apoptosis (IAP) family and was first characterized as
      a candidate gene for spinal muscular atrophy (SMA). The expression of NAIP has
      been thoroughly studied in the central nervous system and overlaps the pattern of
      neurodegeneration in SMA. Recent studies have pointed to a role for NAIP in non
      neuronal cells. We report here the production of a specific anti-NAIP antibody
      and the profile of NAIP expression in human adult tissues by Western blot and
      immunohistochemical detection methods. NAIP was detected in a number of tissues
      by Western blot analysis, but immunohistochemistry revealed that NAIP's presence
      in certain tissues, such as liver, lung, and spleen, is most likely due to
      macrophage infiltration. In the small intestine, the expression of NAIP coincides
      with the expression of p21(WAF1). This observation, coupled with findings from
      other groups, suggests a role for NAIP in increasing the survival of cells
      undergoing terminal differentiation as well as the possibility that the protein
      serves as an intestinal pathogen recognition protein. This manuscript contains
      online supplemental material at http://www.jhc.org. Please visit this article
      online to view these materials.

PMID- 17510376
TI  - Von hippel-lindau: a tumor suppressor links microtubules to ciliogenesis and
      cancer development.
AB  - Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial
      and most sporadic renal cell carcinoma. The tumor suppressor role of the protein
      pVHL is based on its ability to target transcription factors of the hypoxia
      inducible factor family for degradation, but other functions of pVHL are less
      clearly defined. New findings show that pVHL is necessary for cilia formation.
      pVHL interacts with PAR proteins, a complex that specifies the membrane domains
      of polarized epithelial cells, and directs the orientation of growing
      microtubules. Loss of pVHL results in aberrant orientation of newly formed
      microtubules and prevents ciliogenesis. These results add to a growing body of
      evidence linking cilia and the cell cycle and suggest that the tumor suppressor
      role of pVHL may involve previously unrecognized pathways.

PMID- 17510377
TI  - Faithful companions: a proposal for neurooncology trials in pet dogs.
AB  - Although relatively rare, malignant glioma (MG) is frequently used for testing
      novel cancer treatments. However, human MG trials have often been initiated on
      the basis of preclinical models that involve numerous discontinuities with the
      human disease. Below, we discuss various limitations of the mainstay model used
      in MG preclinical research, the murine orthotopic xenograft. After discussing
      alternative model systems like transgenic mouse models and canine xenografts, we
      argue that companion animals with spontaneous brain cancers offer a
      scientifically and ethically attractive system for preclinical testing of novel
      MG interventions. Ethical advantages and practical challenges of companion animal
      brain cancer trials are briefly discussed.

PMID- 17510378
TI  - Towards Clinical Application of Methylated DNA Sequences as Cancer Biomarkers: A
      Joint NCI's EDRN and NIST Workshop on Standards, Methods, Assays, Reagents and
      Tools.
AB  - The workshop report, entitled Towards Clinical Application of Methylated DNA
      Sequences as Cancer Biomarkers: A Joint National Cancer Institute's Early
      Detection Research Network and National Institute of Standards and Technology
      Workshop, presents a summary of the main issues, current challenges, outcomes,
      and recommendations toward application of methylated DNA sequences as cancer
      biomarkers.

PMID- 17510379
TI  - The 3rd Pacific Rim meeting on breast and prostate cancer: progress in hormonal
      carcinogenesis and the enduring influence of Ron Ross.

PMID- 17510380
TI  - MicroRNA: Potential for Cancer Detection, Diagnosis, and Prognosis.

PMID- 17510381
TI  - In the forefront of basic and translational cancer research: Seventh Joint
      Conference of the American Association for Cancer Research and the Japanese
      Cancer Association.

PMID- 17510382
TI  - Meeting report: Translational Research at the Aging and Cancer Interface.

PMID- 17510384
TI  - Extensive methylation is associated with beta-catenin mutations in hepatocellular
      carcinoma: evidence for two distinct pathways of human hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) with p53 mutations is usually characterized by
      extensive chromosomal instability (CIN), whereas those with beta-catenin
      mutations have relatively less CIN and the molecular pathogenesis of these tumors
      is unknown. Methylation of CpG dinucleotides in the promoters of cancer-related
      genes is another characteristic feature of HCCs. The aim of this study was to
      determine the contribution of the methylator phenotype to HCC and its
      relationship to genomic instability. Fractional allelic loss (FAL) was determined
      using 400 microsatellite markers in 81 HCCs and 77 corresponding noncancerous
      livers as a measure of CIN. Methylation of 21 genetic loci was quantitated using
      combined bisulfite restriction analysis. Using hierarchical clustering analysis
      based upon the quantification of methylation levels, all HCCs were segregated
      into two groups characterized by either limited or extensive methylation.
      Mutations in the beta-catenin and p53 genes were determined by DNA sequencing. We
      found that the methylation levels were significantly higher in the HCCs than in
      noncancerous livers in 18 of the 21 loci (P values ranged from 0.035 to <0.0001).
      Among 18 loci, elevated levels of methylation at nine loci were significantly
      associated with beta-catenin mutations (P values ranged from 0.02 to <0.0001). In
      addition, the presence of beta-catenin mutations was associated with HCCs in the
      extensive methylation group (P < 0.0001), whereas p53 mutations correlated with
      high FAL scores (P = 0.0036). These data suggest that HCCs can be classified into
      two distinct categories based upon promoter methylation, CIN, and mutations of
      cancer-related genes. HCCs with extensive methylation harbor frequent beta
      catenin mutations, whereas HCCs with high levels of CIN are associated with p53
      mutations, suggesting the presence of two independent pathways for the
      pathogenesis of HCC.

PMID- 17510383
TI  - Attenuated expression of xeroderma pigmentosum group C is associated with
      critical events in human bladder cancer carcinogenesis and progression.
AB  - Xeroderma pigmentosum group C (XPC) is an important DNA damage recognition
      protein that binds to damaged DNA at a very early stage during DNA repair. The
      XPC protein is also involved in DNA damage-induced cell cycle checkpoint
      regulation and apoptosis. XPC defects are associated with many types of solid
      tumors. The mechanism of the XPC protein in cancer progression, however, remains
      unclear. In this report, we showed the strong correlation between bladder cancer
      progression and attenuated XPC protein expression using tissues derived from
      patients with bladder cancer. The results obtained from our immunohistochemical
      studies further revealed a strong correlation of XPC deficiency, p53 mutation,
      and the degree of malignancy of bladder tumors. In addition, the results obtained
      from our studies have also shown that HT1197 bladder cancer cells, which carry a
      low-level XPC protein, exhibited a decreased DNA repair capability and were
      resistant to cisplatin treatment. When an XPC gene cDNA-expression vector was
      stably transfected into the HT1197 cells, however, the cisplatin treatment
      induced apoptotic cell death was increased. Increased p53 and p73 responses
      following cisplatin treatment were also observed in HT1197 cells stably
      transfected with XPC cDNA. Taken together, these results suggest that XPC
      deficiency is an important contributing factor in bladder tumor progression and
      bladder cancer cell drug resistance.

PMID- 17510385
TI  - Functional analysis of human MLH1 variants using yeast and in vitro mismatch
      repair assays.
AB  - The functional characterization of nonsynonymous single nucleotide polymorphisms
      in human mismatch repair (MMR) genes has been critical to evaluate their
      pathogenicity for hereditary nonpolyposis colorectal cancer. We previously
      established an assay for detecting loss-of-function mutations in the MLH1 gene
      using a dominant mutator effect of human MLH1 expressed in Saccharomyces
      cerevisiae. The purpose of this study is to extend the functional analyses of
      nonsynonymous single nucleotide polymorphisms in the MLH1 gene both in quality
      and in quantity, and integrate the results to evaluate the variants for
      pathogenic significance. The 101 MLH1 variants, which covered most of the
      reported MLH1 nonsynonymous single nucleotide polymorphisms and consisted of one
      3-bp deletion, 1 nonsense and 99 missense variants, were examined for the
      dominant mutator effect by three yeast assays and for the ability of the variant
      to repair a heteroduplex DNA with mismatch bases by in vitro MMR assay. There was
      diversity in the dominant mutator effects and the in vitro MMR activities among
      the variants. The majority of functionally inactive variants were located around
      the putative ATP-binding pocket of the NH(2)-terminal domain or the whole region
      of the COOH-terminal domain. Integrated functional evaluations contribute to a
      better prediction of the cancer risk in individuals or families carrying MLH1
      variants and provide insights into the function-structure relationships in MLH1.

PMID- 17510387
TI  - Transcriptional control of the human high mobility group A1 gene: basal and
      oncogenic Ras-regulated expression.
AB  - Several studies have already shown that the high mobility group A1 (HMGA1) gene
      is up-regulated in most common types of cancer and immortalized tissue culture
      cell lines. HMGA1 expression is also much higher during embryonic development
      than in adult life. The elevated expression of HMGA1 in cancer thus likely occurs
      through oncofetal transcriptional mechanisms, which to date have not been well
      characterized. In the present study, we have cloned and functionally analyzed the
      TATA-less 5'-flanking regulatory region of human HMGA1. We identified two
      proximal regulatory regions that are important for basal transcription and in
      which specificity protein 1 (SP1) and activator protein 1 (AP1) transcription
      factors seem to be the regulating elements. In addition, we showed that the HMGA1
      promoter is strongly inducible by oncogenic Ras, via a distal regulatory region.
      An AP1 site and three SP1-like sites are responsible for this inducible activity.
      An even more convincing finding for a role of oncogenic Ras in the regulation of
      HMGA1 in cancers is the discovery that HMGA1 up-regulation in the HCT116 colon
      cancer cell line is abolished when the mutated Ras allele is removed from these
      cells. Our data constitute the first extensive study of the regulation of basal
      and Ras-induced human HMGA1 gene expression and suggest that the elevated
      expression of HMGA1 in cancer cells requires, among others, a complex cooperation
      between SP1 family members and AP1 factors by the activation of Ras GTPase
      signaling.

PMID- 17510386
TI  - Fundamental differences in cell cycle deregulation in human papillomavirus
      positive and human papillomavirus-negative head/neck and cervical cancers.
AB  - Human papillomaviruses (HPV) are associated with nearly all cervical cancers, 20%
      to 30% of head and neck cancers (HNC), and other cancers. Because HNCs also arise
      in HPV-negative patients, this type of cancer provides unique opportunities to
      define similarities and differences of HPV-positive versus HPV-negative cancers
      arising in the same tissue. Here, we describe genome-wide expression profiling of
      84 HNCs, cervical cancers, and site-matched normal epithelial samples in which we
      used laser capture microdissection to enrich samples for tumor-derived versus
      normal epithelial cells. This analysis revealed that HPV(+) HNCs and cervical
      cancers differed in their patterns of gene expression yet shared many changes
      compared with HPV(-) HNCs. Some of these shared changes were predicted, but many
      others were not. Notably, HPV(+) HNCs and cervical cancers were found to be up
      regulated in their expression of a distinct and larger subset of cell cycle genes
      than that observed in HPV(-) HNC. Moreover, HPV(+) cancers overexpressed testis
      specific genes that are normally expressed only in meiotic cells. Many, although
      not all, of the hallmark differences between HPV(+) HNC and HPV(-) HNC were a
      direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This
      included a novel association of HPV oncogenes with testis-specific gene
      expression. These findings in primary human tumors provide novel biomarkers for
      early detection of HPV(+) and HPV(-) cancers, and emphasize the potential value
      of targeting E6 and E7 function, alone or combined with radiation and/or
      traditional chemotherapy, in the treatment of HPV(+) cancers.

PMID- 17510388
TI  - DJ-1 binds androgen receptor directly and mediates its activity in hormonally
      treated prostate cancer cells.
AB  - The oncogene DJ-1 has been associated with multiple cancers, including prostate
      cancer, where it can be stabilized by androgens and antiandrogens. However,
      little data exist on the expression pattern and function of DJ-1 in prostate
      cancer. To address the function of DJ-1 in prostate, a yeast two-hybrid screen
      was done to identify novel DJ-1 binding proteins. The androgen receptor (AR) was
      identified and confirmed as a DJ-1 binding partner. This is the first evidence
      that DJ-1 directly interacts with AR. We also show that modulation of DJ-1
      expression regulated AR transcriptional activity. Importantly, both the
      subcellular localization of DJ-1 and the interaction with AR are regulated by
      androgens and antiandrogens. Additionally, immunohistochemical staining on two
      human prostate cancer tissue arrays was done providing the first large-scale
      expression analysis of DJ-1 in prostate. DJ-1 expression did not change with
      Gleason pattern but increased after androgen deprivation therapy, indicating that
      it may be involved in the development of androgen independence. These data
      provide a novel mechanism where DJ-1-mediated regulation of AR may promote the
      progression of prostate cancer to androgen independence.

PMID- 17510389
TI  - Expression of nicotinic acetylcholine receptor subunit genes in non-small-cell
      lung cancer reveals differences between smokers and nonsmokers.
AB  - Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors
      (nAChR) on bronchial epithelial cells, can regulate cellular proliferation and
      apoptosis via activating the Akt pathway. Delineation of nAChR subtypes in non
      small-cell lung cancers (NSCLC) may provide information for prevention or
      therapeutic targeting. Expression of nAChR subunit genes in 66 resected primary
      NSCLCs, 7 histologically non-involved lung tissues, 13 NSCLC cell lines, and 6
      human bronchial epithelial cell lines (HBEC) was analyzed with quantitative PCR
      and microarray analysis. Five nonmalignant HBECs were exposed to nicotine in
      vitro to study the variation of nAChR subunit gene expression with nicotine
      exposure and removal. NSCLCs from nonsmokers showed higher expression of nAChR
      alpha6 (P < 0.001) and beta3 (P = 0.007) subunit genes than those from smokers,
      adjusted for gender. In addition, nAChR alpha4 (P < 0.001) and beta4 (P = 0.029)
      subunit gene expression showed significant difference between NSCLCs and normal
      lung. Using Affymetrix GeneChip U133 Sets, 65 differentially expressed genes
      associated with NSCLC nonsmoking nAChR alpha6beta3 phenotype were identified,
      which gave high sensitivity and specificity of prediction. nAChR alpha1, alpha5,
      and alpha7 showed significant reversible changes in expression levels in HBECs
      upon nicotine exposure. We conclude that between NSCLCs from smokers and
      nonsmokers, different nAChR subunit gene expression patterns were found, and a 65
      gene expression signature was associated with nonsmoking nAChR alpha6beta3
      expression. Finally, nicotine exposure in HBECs resulted in reversible
      differences in nAChR subunit gene expression. These results further implicate
      nicotine in bronchial carcinogenesis and suggest targeting nAChRs for prevention
      and therapy in lung cancer.

PMID- 17510390
TI  - Dominant-negative but not gain-of-function effects of a p53.R270H mutation in
      mouse epithelium tissue after DNA damage.
AB  - p53 alterations in human tumors often involve missense mutations that may confer
      dominant-negative or gain-of-function properties. Dominant-negative effects
      result in inactivation of wild-type p53 protein in heterozygous mutant cells and
      as such in a p53 null phenotype. Gain-of-function effects can directly promote
      tumor development or metastasis through antiapoptotic mechanisms or
      transcriptional activation of (onco)genes. Here, we show, using conditional mouse
      technology, that epithelium-specific heterozygous expression of mutant p53 (i.e.,
      the p53.R270H mutation that is equivalent to the human hotspot R273H) results in
      an increased incidence of spontaneous and UVB-induced skin tumors. Expression of
      p53.R270H exerted dominant-negative effects on latency, multiplicity, and
      progression status of UVB-induced but not spontaneous tumors. Surprisingly, gain
      of-function properties of p53.R270H were not detected in skin epithelium.
      Apparently, dominant-negative and gain-of-function effects of mutant p53 are
      highly tissue specific and become most manifest upon stabilization of p53 after
      DNA damage.

PMID- 17510391
TI  - Tumor suppressor activity of CCAAT/enhancer binding protein alpha is
      epigenetically down-regulated in head and neck squamous cell carcinoma.
AB  - Tumor suppressor CCAAT enhancer binding protein alpha (C/EBPalpha) is a
      transcription factor involved in cell cycle control and cellular differentiation.
      In a recent study, microarray expression profiling on head and neck squamous cell
      carcinoma (HNSCC) samples identified significant C/EBPalpha down-regulation,
      correlating with poor prognosis. However, the mechanisms of C/EBPalpha down
      regulation remained elusive. C/EBPalpha has been previously found to provide an
      antiproliferative role in lung cancer, and our laboratory showed that its down
      regulation involves epigenetic mechanisms. This prompted us to investigate the
      involvement of epigenetics in down-regulating C/EBPalpha in HNSCC. Here, we show
      that C/EBPalpha is down-regulated in HNSCC by loss of heterozygosity and DNA
      methylation, but not by gene mutation. We found a consistently methylated
      upstream regulatory region (-1,399 bp to -1,253 bp in relation to the
      transcription start site) in 68% of the HNSCC tumor samples, and DNA
      demethylation using 5-aza-2'-deoxycytidine treatment was able to significantly
      restore C/EBPalpha mRNA expression in the HNSCC cell lines we tested. In
      addition, C/EBPalpha overexpression in a HNSCC cell line (SCC22B) revealed its
      ability to provide tumor suppressor activity in HNSCC in vitro and in vivo. In
      conclusion, we showed for the first time not only that C/EBPalpha has tumor
      suppressor activity in HNSCC, but also that it is down-regulated by DNA promoter
      methylation.

PMID- 17510392
TI  - EGFR-T790M is a rare lung cancer susceptibility allele with enhanced kinase
      activity.
AB  - The use of tyrosine kinase inhibitors (TKI) has yielded great success in
      treatment of lung adenocarcinomas. However, patients who develop resistance to
      TKI treatment often acquire a somatic resistance mutation (T790M) located in the
      catalytic cleft of the epidermal growth factor receptor (EGFR) enzyme. Recently,
      a report describing EGFR-T790M as a germ-line mutation suggested that this
      mutation may be associated with inherited susceptibility to lung cancer. Contrary
      to previous reports, our analysis indicates that the T790M mutation confers
      increased Y992 and Y1068 phosphorylation levels. In a human bronchial epithelial
      cell line, overexpression of EGFR-T790M displayed a growth advantage over wild
      type (WT) EGFR. We also screened 237 lung cancer family probands, in addition to
      45 bronchoalveolar tumors, and found that none of them contained the EGFR-T790M
      mutation. Our observations show that EGFR-T790M provides a proliferative
      advantage with respect to WT EGFR and suggest that the enhanced kinase activity
      of this mutant is the basis for rare cases of inherited susceptibility to lung
      cancer.

PMID- 17510393
TI  - Repression of sestrin family genes contributes to oncogenic Ras-induced reactive
      oxygen species up-regulation and genetic instability.
AB  - Oncogenic mutations within RAS genes and inactivation of p53 are the most common
      events in cancer. Earlier, we reported that activated Ras contributes to
      chromosome instability, especially in p53-deficient cells. Here we show that an
      increase in intracellular reactive oxygen species (ROS) and oxidative DNA damage
      represents a major mechanism of Ras-induced mutagenesis. Introduction of
      oncogenic H- or N-Ras caused elevated intracellular ROS, accumulation of 8-oxo-2'
      deoxyguanosine, and increased number of chromosome breaks in mitotic cells, which
      were prevented by antioxidant N-acetyl-L-cysteine. By using Ras mutants that
      selectively activate either of the three major targets of Ras (Raf, RalGDS, and
      phosphatidylinositol-3-kinase) as well as dominant-negative Rac1 and RalA mutants
      and inhibitors of mitogen-activated protein kinase (MAPK)/extracellular signal
      regulated kinases kinase-1 and p38 MAPKs, we have shown that several Ras
      effectors independently mediate ROS up-regulation. Introduction of oncogenic RAS
      resulted in repression of transcription from sestrin family genes SESN1 and
      SESN3, which encode antioxidant modulators of peroxiredoxins. Inhibition of mRNAs
      from these genes in control cells by RNA interference substantially increased ROS
      levels and mutagenesis. Ectopic expression of SESN1 and SESN3 from lentiviral
      constructs interfered with Ras-induced ROS increase, suggesting their important
      contribution to the effect. The stability of Ras-induced increase in ROS was
      dependent on a p53 function: in the p53-positive cells displaying activation of
      p53 in response to Ras, only transient (4-7 days) elevation of ROS was observed,
      whereas in the p53-deficient cells the up-regulation was permanent. The reversion
      to normal ROS levels in the Ras-expressing p53-positive cells correlated with up
      regulation of p53-responsive genes, including reactivation of SESN1 gene. Thus,
      changes in expression of sestrins can represent an important determinant of
      genetic instability in neoplastic cells showing simultaneous dysfunctions of Ras
      and p53.

PMID- 17510394
TI  - HMGA1 controls transcription of insulin receptor to regulate cyclin D1
      translation in pancreatic cancer cells.
AB  - The HMGA1 proteins act as architectural transcription factors and are involved in
      the regulation of genes important in the process of carcinogenesis. Although
      HMGA1 proteins are overexpressed in most types of cancer, signaling circuits
      regulated by HMGA1 are not clarified in detail. In this study, we show that HMGA1
      proteins promote proliferation of pancreatic cancer cells by accelerating G(1)
      phase progression. Transfection of HMGA1-specific small interfering RNA (siRNA)
      activates the RB-dependent G(1)-phase checkpoint due to the impaired expression
      of cyclin D1. Down-regulation of cyclin D1 after the HMGA1 knockdown is due to
      translational control and involves the repressor of the eukaryotic translation
      initiation factor 4E (eIF4E) 4E-BP1. We show that 4E-BP1 and cyclin D1 act
      downstream of the insulin receptor (IR) in pancreatic cancer cells. At the
      molecular level transcription of the IR is controlled by a CAAT/enhancer binding
      protein beta (C/EBPbeta)/HMGA1 complex. Together, this work defines a novel
      pathway regulated by HMGA1, which contributes to the proliferation of pancreatic
      cancer cells.

PMID- 17510395
TI  - Mitochondrial genetic background modifies breast cancer risk.
AB  - Inefficient mitochondrial electron transport chain (ETC) function has been
      implicated in the vicious cycle of reactive oxygen species (ROS) production that
      may predispose an individual to late onset diseases, such as diabetes,
      hypertension, and cancer. Mitochondrial DNA (mtDNA) variations may affect the
      efficiency of ETC and ROS production, thus contributing to cancer risk. To test
      this hypothesis, we genotyped 69 mtDNA variations in 156 unrelated European
      American females with familial breast cancer and 260 age-matched European
      American female controls. Fisher's exact test was done for each single-nucleotide
      polymorphism (SNP)/haplogroup and the P values were adjusted for multiple testing
      using permutation. Odds ratio (OR) and its 95% confidence interval (95% CI) were
      calculated using the Sheehe correction. Among the 69 variations, 29 were detected
      in the study subjects. Three SNPs, G9055A (OR, 3.03; 95% CI, 1.63-5.63; P =
      0.0004, adjusted P = 0.0057), A10398G (OR, 1.79; 95% CI, 1.14-2.81; P = 0.01,
      adjusted P = 0.19), and T16519C (OR, 1.98; 95% CI, 1.25-3.12; P = 0.0030,
      adjusted P = 0.0366), were found to increase breast cancer risk; whereas T3197C
      (OR, 0.31; 95% CI, 0.13-0.75; P = 0.0043, adjusted P = 0.0526) and G13708A (OR,
      0.47; 95% CI, 0.24-0.92; P = 0.022, adjusted P = 0.267) were found to decrease
      breast cancer risk. Overall, individuals classified as haplogroup K show a
      significant increase in the risk of developing breast cancer (OR, 3.03; 95% CI,
      1.63-5.63; P = 0.0004, adjusted P = 0.0057), whereas individuals bearing
      haplogroup U have a significant decrease in breast cancer risk (OR, 0.37; 95% CI,
      0.19-0.73; P = 0.0023, adjusted P = 0.03). Our results suggest that mitochondrial
      genetic background plays a role in modifying an individual's risk to breast
      cancer.

PMID- 17510396
TI  - The combined effects of xeroderma pigmentosum C deficiency and mutagens on
      mutation rates in the mouse germ line.
AB  - Spontaneous and induced mutation rates at two expanded simple tandem repeat
      (ESTR) loci were studied in the germ line of xeroderma pigmentosum group C (Xpc)
      knockout mice defective in global genome nucleotide excision repair. Spontaneous
      and radiation-induced mutation rates in homozygous Xpc(-/-) males were
      significantly higher than those in isogenic wild-type (Xpc(+/+)) and heterozygous
      (Xpc(+/-)) mice. In contrast, exposure to the monofunctional alkylating agent
      ethylnitrosourea resulted in similar increases in ESTR mutation rates across all
      genotypes. ESTR mutation spectra in the germ line of Xpc(-/-), Xpc(+/-) and
      Xpc(+/+) did not differ. Considering these data and the results of other
      publications, we propose that the Xpc-deficient mice possess a mutator phenotype
      in their germ line and somatic tissues that may significantly enhance
      carcinogenesis across multiple tissues.

PMID- 17510397
TI  - Hint1 inhibits growth and activator protein-1 activity in human colon cancer
      cells.
AB  - There is accumulating evidence that histidine triad (HIT) nucleotide-binding
      protein 1 (HINT1), a member of the evolutionary highly conserved HIT protein
      super family, is a novel tumor suppressor. However, the mechanism of action of
      HINT1 with respect to tumor suppression is not known. In the present study, we
      found that a series of human colon cancer cell lines displayed various levels of
      expression of HINT1, with a very low level in SW480 cells. This cell line also
      displayed partial methylation of the promoter region of the Hint1 gene, and
      treatment of these cells with 5-azadeoxycitidine increased expression of Hint1
      mRNA and protein. Therefore, the decreased expression of HINT1 in SW480 cells
      seems to be due to epigenetic silencing. Increased expression of HINT1 in these
      cells, using a retrovirus vector (pLNCX2) that encodes either wild-type (WT)
      Hint1 or a point mutant (His(112)/Asn(112)) of Hint1, inhibited the proliferation
      of SW480 cells. Because of the important role of the activator protein-1 (AP-1)
      transcription factor in cancer cells, we examined possible effects of HINT1 on AP
      1 transcription factor activity in SW480 cells transfected with an AP-1
      luciferase reporter. We found that cotransfection with a pHA-Hint1 plasmid DNA
      significantly inhibited this activity. Studies with inhibitors indicated that AP
      1 activity in SW480 cells requires the activity of c-Jun NH(2)-terminal kinase
      (JNK) 2 and not JNK1. Cotransfection with the Hint1 plasmid DNA also inhibited AP
      1-luciferase reporter activity in WT mouse embryo fibroblast (MEF) studies, and
      studies with JNK1 deleted or JNK2 deleted MEFs confirmed the essential role for
      JNK2, but not JNK1, in mediating AP-1 activity. Recent studies indicate that the
      protein plenty of SH3 (POSH) provides a scaffold that enhances JNK activity. We
      found that cotransfection of a plasmid DNA encoding POSH stimulated the
      phosphorylation of c-Jun and also AP-1 reporter activity, and cotransfection with
      Hint1 inhibited both of these activities. Furthermore, coimmunoprecipitation
      studies provided evidence that HINT1 forms an in vivo complex with POSH and JNK.
      These results suggest that HINT1 inhibits AP-1 activity by binding to a POSH-JNK2
      complex, thus inhibiting the phosphorylation of c-Jun. This effect could
      contribute to the tumor suppressor activity of HINT1.

PMID- 17510398
TI  - Regulation of Helicobacter pylori cagA expression in response to salt.
AB  - Helicobacter pylori infection and a high dietary salt intake are risk factors for
      the development of gastric adenocarcinoma. In this study, we tested the
      hypothesis that high salt concentrations might alter gene expression in H.
      pylori. Transcriptional profiling experiments indicated that the expression of
      multiple H. pylori genes, including cagA, was regulated in response to the
      concentrations of sodium chloride present in the bacterial culture medium.
      Increased expression of cagA in response to high salt conditions was confirmed by
      the use of transcriptional reporter strains and by immunoblotting. H. pylori CagA
      is translocated into gastric epithelial cells via a type IV secretion pathway,
      and on entry into target cells, CagA undergoes tyrosine phosphorylation and
      causes multiple cellular alterations. Coculture of gastric epithelial cells with
      H. pylori grown under high salt conditions resulted in increased tyrosine
      phosphorylated CagA and increased secretion of interleukin-8 by the epithelial
      cells compared with coculture of the cells with H. pylori grown under low salt
      conditions. Up-regulation of H. pylori cagA expression in response to high salt
      concentrations may be a factor that contributes to the development of gastric
      adenocarcinoma.

PMID- 17510399
TI  - Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of
      F1F0 ATP synthase.
AB  - The antiangiogenic protein angiostatin inhibits ATP synthase on the endothelial
      cell surface, blocking cellular proliferation. To examine the specificity of this
      interaction, we generated monoclonal antibodies (mAb) directed against ATP
      synthase. mAb directed against the beta-catalytic subunit of ATP synthase
      (MAb3D5AB1) inhibits the activity of the F(1) domain of ATP synthase and
      recognizes the catalytic beta-subunit of ATP synthase. We located the antibody
      recognition site of MAb3D5AB1 in domains containing the active site of the beta
      subunit. MAb3D5AB1 also binds to purified Escherichia coli F(1) with an affinity
      25-fold higher than the affinity of angiostatin for this protein. MAb3D5AB1
      inhibits the hydrolytic activity of F(1) ATP synthase at lower concentrations
      than angiostatin. Like angiostatin, MAb3D5AB1 inhibits ATP generation by ATP
      synthase on the endothelial cell surface in acidic conditions, the typical tumor
      microenvironment where cell surface ATP synthase exhibits greater activity.
      MAb3D5AB1 disrupts tube formation and decreases intracellular pH in endothelial
      cells exposed to low extracellular pH. Neither angiostatin nor MAb3D5AB1 showed
      an antiangiogenic effect in the corneal neovascularization assay; however, both
      were effective in the low-pH environment of the chicken chorioallantoic membrane
      assay. Thus, MAb3D5AB1 shows angiostatin-like properties superior to angiostatin
      and may be exploited in cancer chemotherapy.

PMID- 17510400
TI  - High-level expression of chemokine CXCL16 by tumor cells correlates with a good
      prognosis and increased tumor-infiltrating lymphocytes in colorectal cancer.
AB  - CXCL16 is a new member of the chemokine superfamily, which exists in a
      transmembrane as well as a soluble form. Its receptor CXCR6 is detected on CD4(+)
      T cells, CD8(+) T cells, and natural killer T cells. Here, we report a
      significant correlation of CXCL16 expression by tumor cells with the infiltration
      of T cells and prognosis in colorectal cancer (CRC). We first found that CXCL16
      expression was consistently up-regulated more in tumor tissues than in normal
      mucosa derived from the same CRC patients. Four human CRC cell lines also
      expressed CXCL16 mRNA and secreted soluble CXCL16. We next examined the
      expression of CXCL16 and infiltration of lymphocytes in CRC specimens (n = 58) by
      immunohistochemistry. CRC patients with high levels of CXCL16 expression (n = 43)
      had higher levels of CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TIL; P <
      0.01) than those with low levels of CXCL16 expression (n = 15). Furthermore, the
      high CXCL16 expression group showed significantly better prognosis than the low
      CXCL16 expression group (P < 0.05). Collectively, our data suggest that the
      expression of CXCL16 by tumor cells enhances the recruitment of TILs, thereby
      bringing about a better prognosis in CRC. Thus, CXCL16 is a new prognostic
      biomarker and may be useful for the development of a more effective therapeutic
      strategy for CRC.

PMID- 17510402
TI  - The ability of versican to simultaneously cause apoptotic resistance and
      sensitivity.
AB  - Expression of the extracellular matrix proteoglycan versican is associated with
      more than 10 types of cancers, often being secreted by stromal cells in response
      to tumor signals. Previous work in our lab has shown that overexpression of the
      V1 versican isoform in cultured fibroblasts (V1 cells) increases both
      proliferation and apoptotic resistance. We show here that V1 cells induced tumor
      formation in nude mice and that, in keeping with previously shown apoptotic
      resistance, V1 cells have down-regulated Fas mRNA and protein levels.
      Unexpectedly, however, V1 cells were found to be sensitized to a wide range of
      cytotoxic agents. This combination of selective apoptotic resistance and
      sensitivity is often seen in cancer cells. V1 cells were also shown to have high
      resting levels of p53 and murine double minute-2 proteins, correlating with
      apoptotic sensitivity. Treatment with UV radiation induced p21 expression in
      vector-transfected cells but not in V1 cells. As p21 induces cell cycle arrest
      and inhibits apoptosis, its loss in V1 cells, coupled with high resting levels of
      proapoptotic p53, may be at least partially involved in their premature death
      following cytotoxic treatment. This study further supports the importance of
      versican in cancer cell biology and the complexity of apoptosis regulation.

PMID- 17510401
TI  - Expression of p16Ink4a compensates for p18Ink4c loss in cyclin-dependent kinase
      4/6-dependent tumors and tissues.
AB  - Cell cycle progression from G(1) to S phase depends on phosphorylation of pRb by
      complexes containing a cyclin (D type or E type) and cyclin-dependent kinase
      (e.g., cdk2, cdk4, or cdk6). Ink4 proteins function to oppose the action of
      cdk4/6-cyclin D complexes by inhibiting cdk4/6. We employed genetic and
      pharmacologic approaches to study the interplay among Ink4 proteins and cdk4/6
      activity in vivo. Mouse embryo fibroblasts (MEF) lacking p16(Ink4a) and
      p18(Ink4c) showed similar growth kinetics as wild-type MEFs despite increased
      cdk4 activity. In vivo, germline deficiency of p16(Ink4a) and p18(Ink4c) resulted
      in increased proliferation in the intermediate pituitary and pancreatic islets of
      adult mice, and survival of p16(Ink4a-/-);p18(Ink4c-/-) mice was significantly
      reduced due to aggressive pituitary tumors. Compensation among the Ink4 proteins
      was observed both in vivo in p18(Ink4c-/-) mice and in MEFs from p16(Ink4a-/-),
      p18(Ink4c-/-), or p16(Ink4a-/-);p18(Ink4c-/-) mice. Treatment with PD 0332991, a
      specific cdk4/6 kinase inhibitor, abrogated proliferation in those compartments
      where Ink4 deficiency was associated with enhanced proliferation (i.e., islets,
      pituitary, and B lymphocytes) but had no effect on proliferation in other tissues
      such as the small bowel. These data suggest that p16(Ink4a) and p18(Ink4c)
      coordinately regulate the in vivo catalytic activity of cdk4/6 in specific
      compartments of adult mice.

PMID- 17510403
TI  - Inactivation of glutathione peroxidase activity contributes to UV-induced
      squamous cell carcinoma formation.
AB  - Cutaneous squamous cell carcinomas (CSCC) are a common malignancy of
      keratinocytes that arise in sites of the skin exposed to excessive UV radiation.
      In the present study, we show that human SCC cell lines, preneoplastic solar
      keratoses (SK), and CSCC are associated with perturbations in glutathione
      peroxidase (GPX) activity and peroxide levels. Specifically, we found that two of
      three SKs and four of five CSCCs, in vivo, were associated with decreased GPX
      activity and all SKs and CSCCs were associated with an elevated peroxide burden.
      Given the association of decreased GPX activity with CSCC, we examined the basis
      for the GPX deficiency in the CSCCs. Our data indicated that GPX was inactivated
      by a post-translational mechanism and that GPX could be inactivated by increases
      in intracellular peroxide levels. We next tested whether the decreased peroxidase
      activity coupled with an elevated peroxidative burden might contribute to CSCC
      formation in vivo. This was tested in Gpx1(-/-) and Gpx2(-/-) mice exposed to
      solar-simulated UV radiation. These studies showed that Gpx2 deficiency
      predisposed mice to UV-induced CSCC formation. These results suggest that
      inactivation of GPX2 in human skin may be an early event in UV-induced SCC
      formation.

PMID- 17510404
TI  - Rap1 integrates tissue polarity, lumen formation, and tumorigenic potential in
      human breast epithelial cells.
AB  - Maintenance of apico-basal polarity in normal breast epithelial acini requires a
      balance between cell proliferation, cell death, and proper cell-cell and cell
      extracellular matrix signaling. Aberrations in any of these processes can disrupt
      tissue architecture and initiate tumor formation. Here, we show that the small
      GTPase Rap1 is a crucial element in organizing acinar structure and inducing
      lumen formation. Rap1 activity in malignant HMT-3522 T4-2 cells is appreciably
      higher than in S1 cells, their nonmalignant counterparts. Expression of dominant
      negative Rap1 resulted in phenotypic reversion of T4-2 cells, led to the
      formation of acinar structures with correct polarity, and dramatically reduced
      tumor incidence despite the persistence of genomic abnormalities and baseline
      growth. The resulting acini contained prominent central lumina not observed when
      other reverting agents were used. Conversely, expression of dominant-active Rap1
      in T4-2 cells inhibited phenotypic reversion and led to increased invasiveness
      and tumorigenicity. Thus, Rap1 acts as a central regulator of breast
      architecture, with normal levels of activation instructing polarity during acinar
      morphogenesis, and increased activation inducing tumor formation and progression
      to malignancy.

PMID- 17510405
TI  - Chemotherapy-induced thrombocytopenia derives from the selective death of
      megakaryocyte progenitors and can be rescued by stem cell factor.
AB  - Thrombocytopenia is a common side effect of chemotherapy, responsible for
      increased risk of bleeding and delay of treatment schedules in cancer patients.
      It is currently unknown how chemotherapeutic agents affect platelet production
      and whether the platelet precursors megakaryocytes represent a direct target of
      cytotoxic drugs. We investigated the effects of chemotherapeutic agents on
      primary megakaryocytes by using a culture system that recapitulates in vitro
      human megakaryopoiesis and found that cytotoxic drugs predominantly destroyed
      megakaryocytic progenitors at early stages of differentiation. Immature
      megakaryocytes could be protected from chemotherapeutic agents by the cytokine
      stem cell factor (SCF), which binds the c-kit receptor expressed on hematopoietic
      stem and progenitor cells. In chemotherapy-treated megakaryocytes, SCF activated
      Akt, neutralized the mitochondrial apoptotic machinery, and inhibited caspase
      activity. Interfering with Akt activation abrogated the antiapoptotic effects of
      SCF, whereas exogenous expression of constitutively active Akt inhibited drug
      induced apoptosis of primary megakaryocytes, indicating the Akt pathway as
      primarily responsible for SCF-mediated protection of megakaryocyte progenitors.
      These results indicate apoptosis of megakaryocyte progenitors as a major cause of
      chemotherapy-induced thrombocytopenia and suggest that SCF may be used to prevent
      platelet loss in cancer patients with c-kit-negative tumors.

PMID- 17510406
TI  - Carcinoembryonic antigen inhibits anoikis in colorectal carcinoma cells by
      interfering with TRAIL-R2 (DR5) signaling.
AB  - Carcinoembryonic antigen (CEA) is a tumor marker that is associated with
      metastasis, poor response to chemotherapy of colorectal cancer (CRC), and
      anoikis, a form of apoptosis caused by cell detachment from matrix that is
      dependent on TRAIL-R2 (DR5) and caspase-8 activation in CRC. Although CEA is a
      homophilic binding protein that may provide survival signals through homotypical
      cell aggregation, we now report that CEA binds TRAIL-R2 (DR5) directly in two
      hybrid assays to decrease anoikis through the extrinsic pathway. Deletion of the
      PELPK sequence (delPELPK) of CEA (delPELPK CEA) restores sensitivity to anoikis
      while it maintains its cell aggregation function. Wild-type (WT) CEA also
      increases experimental hepatic metastasis, whereas the delPELPK CEA does not.
      Thus, membrane CEA interacts with DR5 to inhibit anoikis and increase metastatic
      potential in CRC.

PMID- 17510407
TI  - Scavenger receptor-A-targeted leukocyte depletion inhibits peritoneal ovarian
      tumor progression.
AB  - Immunosuppressive leukocytes are emerging as a critical factor in facilitating
      tumor progression. These leukocytes are converted by the tumor microenvironment
      to become tolerogenic, facilitate metastasis, and to aid in neovascularization.
      The predominant variety of suppressive leukocytes found in human and murine
      ovarian cancer are called vascular leukocytes (VLC), due to sharing functions and
      cell surface markers of both dendritic cells and endothelial cells. Using the ID8
      murine model of ovarian cancer, the aim of this study was to test the efficacy of
      VLC elimination as an ovarian tumor therapy. We show that carrageenan-mediated
      depletion of peritoneal tumor-associated leukocytes inhibits ovarian tumor
      progression. We then identified scavenger receptor-A (SR-A) as a cell surface
      receptor that is robustly and specifically expressed within human and murine
      ovarian tumor ascites upon VLCs. Administration of anti-SR-A immunotoxin to mice
      challenged with peritoneal ID8 tumors eliminated tumor-associated VLCs and,
      importantly, substantially inhibited peritoneal tumor burden and ascites
      accumulation. Moreover, the toxin required targeting to SR-A because mice that
      received untargeted toxin did not exhibit inhibition of tumor progression. We
      conclude that SR-A constitutes a novel and specific target for efficacious
      immunotherapeutic treatment of peritoneal ovarian cancer.

PMID- 17510408
TI  - Nucleophosmin mediates mammalian target of rapamycin-dependent actin cytoskeleton
      dynamics and proliferation in neurofibromin-deficient astrocytes.
AB  - Neurofibromatosis type 1 (NF1) is a common autosomal dominant tumor
      predisposition syndrome in which affected individuals develop astrocytic brain
      tumors (gliomas). To determine how the NF1 gene product (neurofibromin) regulates
      astrocyte growth and motility relevant to glioma formation, we have used Nf1
      deficient primary murine astrocytes. Nf1(-/-) astrocytes exhibit increased
      protein translation and cell proliferation, which are mediated by Ras-dependent
      hyperactivation of the mammalian target of rapamycin (mTOR) protein, a
      serine/threonine protein kinase that regulates ribosomal biogenesis, protein
      translation, actin cytoskeleton dynamics, and cell proliferation. In this study,
      we show that Nf1-deficient astrocytes have fewer actin stress fibers and exhibit
      increased cell motility compared with wild-type astrocytes, which are rescued by
      pharmacologic and genetic mTOR inhibition. We further show that mTOR-dependent
      regulation of actin stress fiber formation, motility, and proliferation requires
      rapamycin-sensitive activation of the Rac1 GTPase but not elongation factor 4E
      binding protein 1/S6 kinase. Nf1(-/-) astrocytes also exhibit increased protein
      translation and ribosomal biogenesis through increased expression of the
      nucleophosmin (NPM) nuclear-cytoplasmic shuttling protein. We found that NPM
      expression in Nf1(-/-) astrocytes was blocked by rapamycin in vitro and in vivo
      and that expression of a dominant-negative NPM mutant protein in Nf1(-/-)
      astrocytes rescued actin stress fiber formation and restored cell motility and
      proliferation to wild-type levels. Together, these data show that neurofibromin
      regulates actin cytoskeleton dynamics and cell proliferation through a mTOR/Rac1
      dependent signaling pathway and identify NPM as a critical mTOR effector
      mediating these biological properties in Nf1-deficient astrocytes.

PMID- 17510409
TI  - Loss of functional Fas ligand enhances intestinal tumorigenesis in the Min mouse
      model.
AB  - Fas ligand (FasL/CD95L), a member of the tumor necrosis factor family, interacts
      with a specific receptor Fas, ultimately leading to cell death. Tumor expression
      of FasL has been proposed to aid in immune evasion through a "Fas counterattack"
      mechanism but has also been described as a proinflammatory factor. Here, we
      tested the role of FasL in a mouse model of spontaneous tumor development. We
      used the Min mouse in which multiple benign polyps develop in the intestine due
      to a mutation in the Apc tumor suppressor gene. Mutant mice deficient in
      functional FasL, termed gld/gld, were crossed to Min mice to generate tumor-prone
      animals lacking functional FasL. Comparison of FasL-deficient versus proficient
      Min mice revealed a significant increase in polyp number in the gld/gld mice. We
      next assessed immune cell infiltration into adenomas. There was no difference in
      the number of either lymphocytes or macrophages; however, the number of tumor
      infiltrating neutrophils was 3-fold lower in the gld/gld specimens compared with
      controls. Neutrophil migration in vitro was stimulated by wild-type but not
      mutant FasL. In a nontumor-bearing colitis model in vivo, neutrophil recruitment
      to the intestine was also reduced in gld/gld mice. Although the Fas counterattack
      hypothesis suggests that the absence of FasL would result in increased immune
      mediated tumor elimination, the opposite is true in the Min model with lack of
      functional FasL associated with reduced neutrophil influx and increased tumor
      development. Thus, the proinflammatory rather than counterattack role of tumor
      FasL is more relevant.

PMID- 17510410
TI  - Prostate cancer cells with stem cell characteristics reconstitute the original
      human tumor in vivo.
AB  - Cancer may arise from a cancer stem/progenitor cell that shares characteristics
      with its normal counterpart. We report the reconstitution of the original human
      prostate cancer specimen from epithelial cell lines (termed HPET for human
      prostate epithelial/hTERT) derived from this sample. These tumors can be
      described in terms of Gleason score, a classification not applied to any of the
      transgenic mouse models currently developed to mimic human disease.
      Immunohistochemical and Western blot analyses indicate that they do not express
      androgen receptor or p63, similar to that reported for prostate stem cells. These
      cell lines also express embryonic stem markers (Oct4, Nanog, and Sox2) as well as
      early progenitor cell markers (CD44 and Nestin) in vitro. Clonally derived HPET
      cells reconstitute the original human tumor in vivo and differentiate into the
      three prostate epithelial cell lineages, indicating that they arise from a common
      stem/progenitor cell. Serial transplantation experiments reconstitute the tumors,
      suggesting that a fraction of parental or clonally derived HPET cells have self
      renewal potential. Thus, this model may enhance our understanding of human tumor
      development and provide a mechanism for studying cancer stem/progenitor cells in
      differentiation, tumorigenesis, preclinical testing, and the development of drug
      resistance.

PMID- 17510411
TI  - Synergistic activation of the tumor suppressor, HLJ1, by the transcription
      factors YY1 and activator protein 1.
AB  - HLJ1 is a novel tumor and invasion suppressor that inhibits tumorigenesis and
      cancer metastasis. However, the mechanism of HLJ1 activation is currently
      unclear. Here, we identify an enhancer segment in the HLJ1 gene at -2,125 to 
      1,039 bp upstream of the transcription start site. A 50-bp element between -1,492
      and -1,443 bp is the minimal enhancer segment, which includes the activator
      protein 1 (AP-1) site (-1,457 to -1,451 bp), an essential regulatory domain that
      binds the transcriptional factors FosB, JunB, and JunD. Chromatin
      immunoprecipitation assays confirm that these AP-1 family members bind to a
      specific site in the HLJ1 enhancer segment in vivo. Overexpression of either YY1
      at promoter or AP-1 at enhancer results in a 3-fold increase in the
      transcriptional activity of HLJ1. We propose a novel mechanism whereby expression
      of the tumor suppressor, HLJ1, is up-regulated via enhancer AP-1 binding to
      promoter YY1 and the coactivator, p300, through DNA bending and multiprotein
      complex formation. The combined expression of AP-1 and YY1 enhances HLJ1
      expression by more than five times and inhibits in vitro cancer cell invasion.
      Elucidation of the regulatory mechanism of HLJ1 expression may facilitate the
      development of personalized therapy by inhibiting cancer cell proliferation,
      angiogenesis, and metastasis.

PMID- 17510412
TI  - Side population in human lung cancer cell lines and tumors is enriched with stem
      like cancer cells.
AB  - Stem cells have been isolated by their ability to efflux Hoechst 33342 dye and
      are referred to as the "side population" (SP). In this study, we used flow
      cytometry and Hoechst 33342 dye efflux assay to isolate and characterize SP cells
      from six human lung cancer cell lines (H460, H23, HTB-58, A549, H441, and H2170).
      Nonobese diabetic/severe combined immunodeficiency xenograft experiments showed
      that SP cells were enriched in tumor-initiating capability compared with non-SP
      cells. Matrigel invasion assay showed that SP cells also have higher potential
      for invasiveness. Further characterization of this SP phenotype revealed several
      stem cell properties. We found evidence for repopulating ability by SP to
      regenerate a population resembling the original population. SP displayed elevated
      expression of ABCG2 as well as other ATP-binding cassette transporters and showed
      resistance to multiple chemotherapeutic drugs. Human telomerase reverse
      transcriptase expression was higher in the SP, suggesting that this fraction may
      represent a reservoir with unlimited proliferative potential for generating
      cancer cells. mRNA levels of minichromosome maintenance (MCM) 7, a member of the
      MCM family of proteins critical to the DNA replication complex, were lower in SP
      cells, suggesting that a majority of the SP fraction was in the G(0) quiescent
      state. Sixteen clinical lung cancer samples also displayed a smaller but
      persistent SP population. These findings indicate that SP is an enriched source
      of lung tumor-initiating cells with stem cell properties and may be an important
      target for effective therapy and a useful tool to investigate the tumorigenic
      process.

PMID- 17510413
TI  - Ras transformation of RIE-1 cells activates cap-independent translation of
      ornithine decarboxylase: regulation by the Raf/MEK/ERK and phosphatidylinositol 3
      kinase pathways.
AB  - Ornithine decarboxylase (ODC) is the first and generally rate-limiting enzyme in
      polyamine biosynthesis. Deregulation of ODC is critical for oncogenic growth, and
      ODC is a target of Ras. These experiments examine translational regulation of ODC
      in RIE-1 cells, comparing untransformed cells with those transformed by an
      activated Ras12V mutant. Analysis of the ODC 5' untranslated region (5'UTR)
      revealed four splice variants with the presence or absence of two intronic
      sequences. All four 5'UTR species were found in both cell lines; however,
      variants containing intronic sequences were more abundant in Ras-transformed
      cells. All splice variants support internal ribosome entry site (IRES)-mediated
      translation, and IRES activity is markedly elevated in cells transformed by Ras.
      Inhibition of Ras effector targets indicated that the ODC IRES element is
      regulated by the phosphorylation status of the translation factor eIF4E.
      Dephosphorylation of eIF4E by inhibition of mitogen-activated
      protein/extracellular signal-regulated kinase (ERK) kinase (MEK) or the eIF4E
      kinase Mnk1/2 increases ODC IRES activity in both cell lines. When both the
      Raf/MEK/ERK and phosphatidylinositol 3-kinase/mammalian target of rapamycin
      pathways are inhibited in normal cells, ODC IRES activity is very low and cells
      arrest in G(1). When these pathways are inhibited in Ras-transformed cells, cell
      cycle arrest does not occur and ODC IRES activity increases, helping to maintain
      high ODC activity.

PMID- 17510414
TI  - Modulation of intracellular ceramide using polymeric nanoparticles to overcome
      multidrug resistance in cancer.
AB  - Although multidrug resistance (MDR) is known to develop through a variety of
      molecular mechanisms within the tumor cell, many tend to converge toward the
      alteration of apoptotic signaling. The enzyme glucosylceramide synthase (GCS),
      responsible for bioactivation of the proapoptotic mediator ceramide to a
      nonfunctional moiety glucosylceramide, is overexpressed in many MDR tumor types
      and has been implicated in cell survival in the presence of chemotherapy. The
      purpose of this study was to investigate the therapeutic strategy of
      coadministering ceramide with paclitaxel, a commonly used chemotherapeutic agent,
      in an attempt to restore apoptotic signaling and overcome MDR in the human
      ovarian cancer cell line SKOV3. Poly(ethylene oxide)-modified poly(epsilon
      caprolactone) (PEO-PCL) nanoparticles were used to encapsulate and deliver the
      therapeutic agents for enhanced efficacy. Results show that indeed the cotherapy
      eradicates the complete population of MDR cancer cells when they are treated at
      their IC(50) dose of paclitaxel. More interestingly, when the cotherapy was
      combined with the properties of nanoparticle drug delivery, the MDR cells can be
      resensitized to a dose of paclitaxel near the IC(50) of non-MDR (drug sensitive)
      cells, indicating a 100-fold increase in chemosensitization via this approach.
      Molecular analysis of activity verified the hypothesis that the efficacy of this
      therapeutic approach is indeed due to a restoration in apoptotic signaling,
      although the beneficial properties of PEO-PCL nanoparticle delivery seemed to
      enhance the therapeutic success even further, showing the promising potential for
      the clinical use of this therapeutic strategy to overcome MDR.

PMID- 17510415
TI  - Tumor angiogenesis promoted by ex vivo differentiated endothelial progenitor
      cells is effectively inhibited by an angiogenesis inhibitor, TK1-2.
AB  - Neovascularization plays a critical role in the growth and metastatic spread of
      tumors and involves recruitment of circulating endothelial progenitor cells (EPC)
      from bone marrow as well as sprouting of preexisting endothelial cells. In this
      study, we examined if EPCs could promote tumor angiogenesis and would be an
      effective cellular target for an angiogenesis inhibitor, the recombinant kringle
      domain of tissue-type plasminogen activator (TK1-2). When TK1-2 was applied in
      the ex vivo culture of EPCs isolated from human cord blood, TK1-2 inhibited
      adhesive differentiation of mononuclear EPCs into endothelial-like cells. In
      addition, it inhibited the migration of ex vivo cultivated EPCs and also
      inhibited their adhesion to fibronectin matrix or endothelial cell monolayer.
      When A549 cancer cells were coimplanted along with ex vivo cultivated EPCs s.c.
      in nude mice, the tumor growth was increased. However, the tumor growth and the
      vascular density of tumor tissues increased by coimplanted EPCs were decreased
      upon TK1-2 treatment. Accordingly, TK1-2 treatment reduced the remaining number
      of EPCs in tumor tissues and their incorporation into the host vascular channels.
      In addition, overall expression levels of vascular endothelial growth factor
      (VEGF) and von Willebrand factor in tumor tissues were decreased upon TK1-2
      treatment. Interestingly, strong VEGF expression by implanted EPCs was decreased
      by TK1-2. Finally, we confirmed in vitro that TK1-2 inhibited VEGF secretion of
      EPCs. TK1-2 also inhibited endothelial cell proliferation and migration induced
      by the conditioned medium of EPCs. Therefore, we concluded that EPCs, as well as
      mature endothelial cells, could be an important target of TK1-2.

PMID- 17510416
TI  - Copper-transporting P-type ATPase, ATP7A, confers multidrug resistance and its
      expression is related to resistance to SN-38 in clinical colon cancer.
AB  - We and others have shown that the copper transporters ATP7A and ATP7B play a role
      in cellular resistance to cis-diaminedichloroplatinum (II) (CDDP). In this study,
      we found that ATP7A transfection of Chinese hamster ovary cells (CHO-K1) and
      fibroblasts isolated from Menkes disease patients enhanced resistance not only to
      CDDP but also to various anticancer drugs, such as vincristine, paclitaxel, 7
      ethyl-10-hydroxy-camptothecin (SN-38), etoposide, doxorubicin, mitoxantron, and 7
      ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11). ATP7A
      preferentially localized doxorubicin fluorescence to the Golgi apparatus in
      contrast to the more intense nuclear staining of doxorubicin in the parental
      cells. Brefeldin A partially and monensin completely altered the distribution of
      doxorubicin to the nuclei in the ATP7A-expressing cells. ATP7A expression also
      enhanced the efflux rates of doxorubicin and SN-38 from cells and increased the
      uptake of SN-38 in membrane vesicles. These findings strongly suggested that
      ATP7A confers multidrug resistance to the cells by compartmentalizing drugs in
      the Golgi apparatus and by enhancing efflux of these drugs, and the trans-Golgi
      network has an important role of ATP7A-related drug resistance. ATP7A was
      expressed in 8 of 34 (23.5%) clinical colon cancer specimens but not in the
      adjacent normal epithelium. Using the histoculture drug response assay that is
      useful for the prediction of drug sensitivity of clinical cancers, ATP7A
      expressing colon cancer cells were significantly more resistant to SN-38 than
      ATP7A-negative cells. Thus, ATP7A confers resistance to various anticancer agents
      on cancer cells and might be a good index of drug resistance in clinical colon
      cancers.

PMID- 17510417
TI  - Molecular basis of the synergistic antiangiogenic activity of bevacizumab and
      mithramycin A.
AB  - The impact of antiangiogenic therapy on the Sp1/vascular endothelial growth
      factor (VEGF) pathway and that of alteration of Sp1 signaling on the efficacy of
      antiangiogenic therapy is unclear, yet understanding their interactions has
      significant clinical implications. Treatment with bevacizumab, a neutralizing
      antibody against VEGF, suppressed human pancreatic cancer growth in nude mice.
      Gene expression analyses revealed that this treatment substantially up-regulated
      the expression of Sp1 and its downstream target genes, including VEGF and
      epidermal growth factor receptor, in tumor tissues, whereas it did not have this
      effect on pancreatic cancer cells in culture. Treatment with mithramycin A, an
      Sp1 inhibitor, suppressed the expression of Sp1 and its downstream target genes
      in both cell culture and tumors growing in nude mice. Combined treatment with
      bevacizumab and mithramycin A produced synergistic tumor suppression, which was
      consistent with suppression of the expression of Sp1 and its downstream target
      genes. Thus, treatment with bevacizumab may block VEGF function but activate the
      pathway of its expression via positive feedback. Given the fact that Sp1 is an
      important regulator of the expression of multiple angiogenic factors, bevacizumab
      initiated up-regulation of Sp1 and subsequent overexpression of its downstream
      target genes may profoundly affect the potential angiogenic phenotype and
      effectiveness of antiangiogenic strategies for human pancreatic cancer.
      Therefore, this study is the first to show the significance and clinical
      implications of alteration of Sp1 signaling in antiangiogenic therapy for
      pancreatic cancer and other cancers.

PMID- 17510418
TI  - HIV protease inhibitors enhance the efficacy of irradiation.
AB  - Tumor vascular endothelium is rather resistant to the cytotoxic effects of
      radiation. The HIV protease inhibitors (HPI) amprenavir, nelfinavir, and
      saquinavir have previously been shown to sensitize tumor cells to the cytotoxic
      effects of radiation. Additionally, this class of drug has been shown to inhibit
      angiogenesis and tumor cell migration. Therefore, in the current study, we wanted
      to determine whether HPIs could enhance the effect of radiation on endothelial
      function. Our study shows that HPIs, particularly nelfinavir, significantly
      enhance radiations effect on human umbilical vein endothelial cells (HUVEC) and
      tumor vascular endothelium. We show that pretreatment of HUVEC with nelfinavir
      results in enhanced cytotoxicity, including increased apoptosis, when combined
      with radiation. Moreover, using several functional assays, we show that
      combination treatment effectively blocks endothelial cell migration and
      organization. These findings were accompanied by attenuation of Akt
      phosphorylation, a known pathway for radioresistance. Last, in vivo analysis of
      tumor microvasculature destruction showed a more than additive effect for
      nelfinavir and radiation. This study shows that HPIs can enhance the effect of
      ionizing radiation on vascular endothelium. Therefore, the Food and Drug
      Administration-approved drug, nelfinavir, may be an effective radiosensitizer in
      the clinic.

PMID- 17510419
TI  - Honokiol induces a necrotic cell death through the mitochondrial permeability
      transition pore.
AB  - Previous reports have shown that honokiol induces apoptosis in numerous cancer
      cell lines and showed preclinical efficacies against apoptosis-resistant B-cell
      chronic lymphocytic leukemia and multiple myeloma cells from relapse-refractory
      patients. Here, we show that honokiol can induce a cell death distinct from
      apoptosis in HL60, MCF-7, and HEK293 cell lines. The death was characterized by a
      rapid loss of integrity of plasma membrane without externalization of
      phosphatidyl serine. The broad caspase inhibitor z-VAD-fmk failed to prevent this
      cell death. Consistently, caspase activation and DNA laddering were not observed.
      The death was paralleled by a rapid loss of mitochondrial membrane potential,
      which was mechanistically associated with the mitochondrial permeability
      transition pore regulated by cyclophilin D (CypD) based on the following
      evidence: (a) cyclosporin A, an inhibitor of CypD (an essential component of the
      mitochondrial permeability transition pore), effectively prevented honokiol
      induced cell death and loss of mitochondrial membrane potential; (b) inhibition
      of CypD by RNA interference blocked honokiol-induced cell death; (c) CypD up
      regulated by honokiol was correlated with the death rates in HL60, but not in
      K562 cells, which underwent apoptosis after being exposed to honokiol. We further
      showed that honokiol induced a CypD-regulated death in primary human acute
      myelogenous leukemia cells, overcame Bcl-2 and Bcl-X(L)-mediated apoptotic
      resistance, and was effective against HL60 cells in a pilot in vivo study. To the
      best of our knowledge, this is the first report to document an induction of
      mitochondrial permeability transition pore-associated cell death by honokiol.

PMID- 17510420
TI  - ERRgamma suppresses cell proliferation and tumor growth of androgen-sensitive and
      androgen-insensitive prostate cancer cells and its implication as a therapeutic
      target for prostate cancer.
AB  - Estrogen receptor-related receptors (ERR) are orphan nuclear receptors, which are
      constitutively activated without estrogen binding. Recent evidence indicates that
      the ligand-independent ERRs may be involved in similar ER-mediated regulatory
      pathways and modulate estrogen responsiveness in certain target cells. We
      recently showed that an ERR subtype, ERRgamma, is coexpressed with ERbeta in
      normal human prostatic epithelial cells and exhibits reduced expression in many
      prostate cancer cell lines and clinical neoplastic prostate tissues. Based on
      this, we hypothesize that ERRgamma may have growth regulatory roles in prostate
      and prostate cancer. We showed in this study that ERRgamma was expressed in
      epithelial cell nuclei in fetal and pubertal human prostates, whereas its nuclear
      expression became reduced in advanced prostate cancer lesions. Stable ERRgamma
      expression by retroviral transduction suppressed significantly both in vitro cell
      growth and in vivo tumorigenicity of two prostate cancer cell lines, LNCaP and
      DU145, as evidenced by a cell-cycle arrest at G(1)-S transition and also
      induction of two cyclin-dependent kinase inhibitors p21(WAF1/CIP1) and p27(KIP1).
      We further showed by reporter assay that induction of p21 and p27 by ERRgamma was
      mediated through direct transactivation of their gene promoters. Moreover, we
      also showed that a selective ERRgamma-agonist, DY131, could potentiate the
      ERRgamma-induced growth inhibition in LNCaP-ERRgamma and DU145-ERRgamma cells in
      a dose-dependent manner compared with respective parental cells. Taken together,
      our results show that ERRgamma may perform an antiproliferative or tumor
      suppressing function in prostate cancer cells. More importantly, our results
      suggest that ERRgamma could be a novel therapeutic target for prostate cancer
      treatment.

PMID- 17510421
TI  - P-glycoprotein mediates celecoxib-induced apoptosis in multiple drug-resistant
      cell lines.
AB  - In several neoplastic diseases, including hepatocellular carcinoma, the
      expression of P-glycoprotein and cyclooxygenase-2 (COX-2) are often increased and
      involved in drug resistance and poor prognosis. P-glycoprotein, in addition to
      drug resistance, blocks cytochrome c release, preventing apoptosis in tumor
      cells. Because COX-2 induces P-glycoprotein expression, we evaluated the effect
      of celecoxib, a specific inhibitor of COX-2 activity, on P-glycoprotein-mediated
      resistance to apoptosis in cell lines expressing multidrug resistant (MDR)
      phenotype. Experiments were done using MDR-positive and parental cell lines at
      basal conditions and after exposure to 10 or 50 micromol/L celecoxib. We found
      that 10 micromol/L celecoxib reduced P-glycoprotein, Bcl-x(L), and Bcl-2
      expression, and induced translocation of Bax from cytosol to mitochondria and
      cytochrome c release into cytosol in MDR-positive hepatocellular carcinoma cells.
      This causes the activation of caspase-3 and increases the number of cells going
      into apoptosis. No effect was shown on parental drug-sensitive or on MDR-positive
      hepatocellular carcinoma cells after transfection with MDR1 small interfering
      RNA. Interestingly, although inhibiting COX-2 activity, 50 micromol/L celecoxib
      weakly increased the expression of COX-2 and P-glycoprotein and did not alter Bcl
      x(L) and Bcl-2 expression. In conclusion, these results show that relatively low
      concentrations of celecoxib induce cell apoptosis in MDR cell lines. This effect
      is mediated by P-glycoprotein and suggests that the efficacy of celecoxib in the
      treatment of different types of cancer may depend on celecoxib concentration and
      P-glycoprotein expression.

PMID- 17510422
TI  - Armed antibodies targeting the mucin repeats of the ovarian cancer antigen,
      MUC16, are highly efficacious in animal tumor models.
AB  - MUC16 is a well-validated cell surface marker for serous adenocarcinomas of the
      ovary and other gynecologic malignancies that is distinguished by highly
      repetitive sequences ("mucin repeats") in the extracellular domain (ECD). We
      produced and compared two monoclonal antibodies: one (11D10) recognizing a
      unique, nonrepeating epitope in the ECD and another (3A5) that recognizes the
      repeats and binds multiple sites on each MUC16 protein. 3A5 conjugated to
      cytotoxic drugs exhibited superior toxicity against tumor cells in vitro and in
      tumor xenograft models compared with antibody-drug conjugates of 11D10.
      Importantly, drug conjugates of 3A5 were well tolerated in primates at levels in
      excess of therapeutic doses. Additionally, the presence of circulating CA125 in a
      rat model did not exacerbate the toxicity of 3A5 drug conjugates. We conclude
      that targeting the repeat MUC16 domains, thereby increasing cell-associated
      levels of drug-conjugated antibody, provides superior efficacy in vitro and in
      vivo without compromising safety.

PMID- 17510424
TI  - The antibody-mediated targeted delivery of interleukin-15 and GM-CSF to the tumor
      neovasculature inhibits tumor growth and metastasis.
AB  - Tumor-targeting immunocytokines represent a new class of anticancer
      pharmaceutical agents, which often display a superior therapeutic index compared
      with the corresponding unconjugated cytokines. In this article, we have studied
      the anticancer properties of interleukin-15 (IL-15) and granulocyte macrophage
      colony-stimulating factor (GM-CSF), fused to the human antibody fragment
      scFv(L19), specific to the EDB domain of fibronectin, a marker of angiogenesis.
      The immunocytokines L19-IL-15 and L19-GM-CSF were expressed in mammalian cells
      and purified to homogeneity, revealing no loss of cytokine activity in in vitro
      assays. Furthermore, the ability of the two immunocytokines to selectively
      localize to tumors in vivo was confirmed by biodistribution analysis with
      radioiodinated protein preparations. L19-IL-15 and L19-GM-CSF displayed a potent
      antitumor activity both in s.c. and in metastatic F9 and C51 murine models of
      cancer in immunocompetent mice. This therapeutic action was superior compared
      with IL-15-based and GM-CSF-based fusion proteins, containing antibodies of
      irrelevant specificity in the mouse, which were used as non-tumor-targeting
      controls. For both L19-IL-15 and L19-GM-CSF immunocytokines, CD8(+) T cells
      seemed to mostly contribute to the therapeutic action as shown by in vivo cell
      depletion experiments. The results presented in this article are of clinical
      significance, considering the fact that the sequence of EDB is identical in mouse
      and man and that the tumor-targeting ability of the L19 antibody has been
      extensively shown in clinical trials in patients with cancer.

PMID- 17510423
TI  - Mutations in BRAF and KRAS converge on activation of the mitogen-activated
      protein kinase pathway in lung cancer mouse models.
AB  - Mutations in the BRAF and KRAS genes occur in approximately 1% to 2% and 20% to
      30% of non-small-cell lung cancer patients, respectively, suggesting that the
      mitogen-activated protein kinase (MAPK) pathway is preferentially activated in
      lung cancers. Here, we show that lung-specific expression of the BRAF V600E
      mutant induces the activation of extracellular signal-regulated kinase (ERK)-1/2
      (MAPK) pathway and the development of lung adenocarcinoma with bronchioloalveolar
      carcinoma features in vivo. Deinduction of transgene expression led to dramatic
      tumor regression, paralleled by dramatic dephosphorylation of ERK1/2, implying a
      dependency of BRAF-mutant lung tumors on the MAPK pathway. Accordingly, in vivo
      pharmacologic inhibition of MAPK/ERK kinase (MEK; MAPKK) using a specific MEK
      inhibitor, CI-1040, induced tumor regression associated with inhibition of cell
      proliferation and induction of apoptosis in these de novo lung tumors. CI-1040
      treatment also led to dramatic tumor shrinkage in murine lung tumors driven by a
      mutant KRas allele. Thus, somatic mutations in different signaling intermediates
      of the same pathway induce exquisite dependency on a shared downstream effector.
      These results unveil a potential common vulnerability of BRAF and KRas mutant
      lung tumors that potentially affects rational deployment of MEK targeted
      therapies to non-small-cell lung cancer patients.

PMID- 17510425
TI  - Suicide gene therapy of human colon carcinoma xenografts using an armed oncolytic
      adenovirus expressing carboxypeptidase G2.
AB  - We have designed a targeted systemic suicide gene therapy that combines the
      advantages of tumor-selective gene expression, using the human telomerase
      promoter (hTERT), with the beneficial effects of an oncolytic adenovirus to
      deliver the gene for the prodrug-activating enzyme carboxypeptidase G2 (CPG2) to
      tumors. Following delivery of the vector (AdV.hTERT-CPG2) and expression of CPG2
      in cancer cells, the prodrug ZD2767P was administered for conversion by CPG2 to a
      cytotoxic drug. This system is sometimes termed gene-directed enzyme prodrug
      therapy (GDEPT). Here, we have shown that it is applicable to 10 human colorectal
      carcinoma cell lines with a direct correlation between viral toxicity and CPG2
      production. SW620 xenografts were selected for analysis and were significantly
      reduced or eradicated after a single administration of AdV.hTERT-CPG2 followed by
      a prodrug course. The oncolytic effect of adenovirus alone did not result in DNA
      cross-links or apoptosis, whereas DNA cross-links and apoptosis occurred
      following prodrug administration, showing the combined beneficial effects of the
      GDEPT system. The apoptotic regions extended beyond the areas of CPG2 expression
      in the tumors, indicative of significant bystander effects in vivo. Higher
      concentrations of vector particles and CPG2 were found in the AdV.hTERT-CPG2 plus
      prodrug-treated tumors compared with the virus alone, showing an unexpected
      beneficial and cooperative effect between the vector and GDEPT. This is the first
      time that a tumor-selective GDEPT vector has been shown to be effective in
      colorectal carcinoma and that apoptosis and significant bystander effects have
      been identified as the mechanisms of cytotoxicity within the tumor.

PMID- 17510426
TI  - MMP-9 short interfering RNA induced senescence resulting in inhibition of
      medulloblastoma growth via p16(INK4a) and mitogen-activated protein kinase
      pathway.
AB  - The involvement of matrix metalloproteinases (MMP) has been suggested in cellular
      mechanisms leading to medulloblastoma, the most common malignant brain tumor in
      children. A significant association of the expression levels of MMP-9 with
      survival and M stage suggests that patients with medulloblastoma metastatic
      disease at diagnosis may benefit from the anti-MMP therapy. Here, we have
      evaluated the tumorigenicity of medulloblastoma cells after infection with an
      adenovirus containing a 21-bp short interfering RNA sequence of the human MMP-9
      gene (Ad-MMP-9). Infection of Daoy medulloblastoma cells with Ad-MMP-9 reduced
      MMP-9 activity and protein levels compared with parental and Ad-SV controls. Ad
      MMP-9 decreased the number of viable Daoy cells in a concentration-dependent
      manner. Fluorescence-activated cell sorting analysis indicated that Ad-MMP-9
      infection caused a dose-dependent cell cycle arrest in the G(0)-G(1) phase. Ad
      MMP-9-induced cell cycle arrest seems to be mediated by the extracellular signal
      regulated kinase/mitogen-activated protein kinase pathway and the cell cycle
      inhibitor p16(INK4a) and is phenotypically indistinguishable from senescence. Ad
      MMP-9 treatment inhibited medulloblastoma tumor growth in an intracranial model
      and was mediated by up-regulation of p16 expression. These studies validate the
      usefulness of targeting MMP-9 and provide a novel perspective in the treatment of
      medulloblastoma.

PMID- 17510427
TI  - Differential effects of targeted disruption of thiopurine methyltransferase on
      mercaptopurine and thioguanine pharmacodynamics.
AB  - The recessive deficiency in thiopurine methyltransferase (TPMT), caused by germ
      line polymorphisms in TPMT, can cause severe toxicity after mercaptopurine.
      However, the significance of heterozygosity and the effect of the polymorphism on
      thioguanine or in the absence of thiopurines is not known. To address these
      issues, we created a murine knockout of Tpmt. Pharmacokinetic and pharmacodynamic
      studies of mercaptopurine and thioguanine were done in Tpmt(-/-), Tpmt(+/-), and
      Tpmt(+/+) mice and variables were compared among genotypes. Methylated thiopurine
      and thioguanine nucleotide metabolites differed among genotypes after treatment
      with mercaptopurine (P < 0.0001 and P = 0.044, respectively) and thioguanine (P =
      0.011 and P = 0.002, respectively). Differences in toxicity among genotypes were
      more pronounced following treatment with 10 daily doses of mercaptopurine at 100
      mg/kg/d (0%, 68%, and 100% 50-day survival; P = 0.0003) than with thioguanine at
      5 mg/kg/d (0%, 33%, and 50% 15-day survival; P = 0.07) in the Tpmt(-/-), Tpmt(+/
      ), and Tpmt(+/+) genotypes, respectively. Myelosuppression and weight loss
      exhibited a haploinsufficient phenotype after mercaptopurine, whereas
      haploinsufficiency was less prominent with thioguanine. In the absence of drug
      challenge, there was no apparent phenotype. The murine model recapitulates many
      clinical features of the human polymorphism; indicates that mercaptopurine is
      more affected by the TPMT polymorphism than thioguanine; and provides a
      preclinical system for establishing safer regimens of genetically influenced
      antileukemic drug therapy.

PMID- 17510428
TI  - The farnesyltransferase inhibitor R115777 up-regulates the expression of death
      receptor 5 and enhances TRAIL-induced apoptosis in human lung cancer cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially
      induces apoptosis in transformed or malignant cells, thus exhibiting potential as
      a tumor-selective apoptosis-inducing cytokine for cancer treatment. Many studies
      have shown that the apoptosis-inducing activity of TRAIL can be enhanced by
      various cancer therapeutic agents. R115777 (tipifarnib) is the first
      farnesyltransferase inhibitor (FTI) that showed clinical activity in myeloid
      malignancies. In general, R115777, like other FTIs, exerts relatively weak
      effects on the induction of apoptosis in cancer cells with undefined
      mechanism(s). In the current study, we studied its effects on the growth of human
      lung cancer cells, including induction of apoptosis, and examined potential
      underlying mechanisms for these effects. We showed that R115777 induced apoptosis
      in human lung cancer cells, in addition to inducing G(1) or G(2)-M arrest.
      Moreover, we found that R115777 up-regulated the expression of death receptor 5
      (DR5), an important death receptor for TRAIL, and exhibited an augmented effect
      on the induction of apoptosis when combined with recombinant TRAIL. Blockage of
      DR5 induction by small interfering RNA (siRNA) abrogated the ability of R115777
      to enhance TRAIL-induced apoptosis, indicating that R115777 augments TRAIL
      induced apoptosis through up-regulation of DR5 expression. Thus, our findings
      show the efficacy of R115777 in human lung cancer cells and suggest that R115777
      may be used clinically in combination with TRAIL for treatment of human lung
      cancer.

PMID- 17510429
TI  - The proteasome inhibitor PS-341 (bortezomib) up-regulates DR5 expression leading
      to induction of apoptosis and enhancement of TRAIL-induced apoptosis despite up
      regulation of c-FLIP and survivin expression in human NSCLC cells.
AB  - The proteasome inhibitor PS-341 (bortezomib or Velcade), an approved drug for
      treatment of patients with multiple myeloma, is currently being tested in
      clinical trials against various malignancies, including lung cancer. Preclinical
      studies have shown that PS-341 induces apoptosis and enhances tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human
      cancer cells with undefined mechanisms. In the present study, we show that PS-341
      induced caspase-8-dependent apoptosis, cooperated with TRAIL to induce apoptosis,
      and up-regulated death receptor 5 (DR5) expression in human non-small cell lung
      cancer (NSCLC) cells. DR5 induction correlated with the ability of PS-341 to
      induce apoptosis. Blockage of PS-341-induced DR5 up-regulation using DR5 small
      interfering RNA (siRNA) rendered cells less sensitive to apoptosis induced by
      either PS-341 or its combination with TRAIL, indicating that DR5 up-regulation
      mediates PS-341-induced apoptosis and enhancement of TRAIL-induced apoptosis in
      human NSCLC cells. We exclude the involvement of c-FLIP and survivin in mediating
      these events because c-FLIP (i.e., FLIP(S)) and survivin protein levels were
      actually elevated on exposure to PS-341. Reduction of c-FLIP with c-FLIP siRNA
      sensitized cells to PS-341-induced apoptosis, suggesting that c-FLIP elevation
      protects cells from PS-341-induced apoptosis. Thus, the present study highlights
      the important role of DR5 up-regulation in PS-341-induced apoptosis and
      enhancement of TRAIL-induced apoptosis in human NSCLC cells.

PMID- 17510430
TI  - Survivin, a member of the inhibitor of apoptosis family, is induced by
      photodynamic therapy and is a target for improving treatment response.
AB  - We observed that photodynamic therapy (PDT) induces the expression and
      phosphorylation of the inhibitor of apoptosis (IAP) protein survivin in murine
      and human cancer cells and tumors. Survivin inhibits caspase-9, blocks apoptosis,
      and is associated with resistance to chemotherapy and radiation. Survivin is a
      client protein for the 90-kDa heat shock protein (Hsp-90), and the binding of
      survivin to Hsp-90 assists in the maturation, proper folding, assembly, and
      transport of this IAP protein. A derivative of the antibiotic geldanamycin, 17
      allylamino-17-demethoxygeldanamycin (17-AAG), interferes with proper binding of
      client proteins, such as survivin, to Hsp-90 and leads to misfolding of client
      proteins, ubiquination, and proteasome degradation. We hypothesized that PDT
      efficacy may be reduced by treatment-mediated expression and phosphorylation of
      survivin, and therefore, targeting the survivin pathway could increase PDT
      responsiveness. To address this hypothesis, we examined cellular and molecular
      responses following exposure to PDT, 17-AAG, and the combination of PDT plus 17
      AAG in human BT-474 breast cancer cells using Photofrin and NPe6 as
      photosensitizers. Cells treated with the combination of PDT and 17-AAG exhibited
      decreased expression of the Hsp-90 client proteins phosphorylated survivin,
      phosphorylated Akt, and Bcl-2. The decreased expression of these client proteins
      was accompanied by higher apoptotic indexes and increased cytotoxicity. To
      confirm a specific role for survivin in modulating PDT, we used a human melanoma
      cell line, YUSAC2/T34A-C4, stably transfected with an inducible dominant-negative
      survivin gene under the control of a tetracycline-regulated (tet-off) promoter.
      PDT treatment of melanoma cells expressing the dominant-negative survivin
      resulted in increased cleavage of the caspase substrate poly(ADP-ribose)
      polymerase, apoptosis, and cytotoxicity when compared with results following PDT
      of the same melanoma cell line expressing wild-type survivin. These results show
      for the first time that targeting survivin and possibly other Hsp-90 client
      proteins improves in vitro PDT responsiveness and suggest that manipulation of
      the antiapoptotic pathway maintained by survivin may enhance PDT-mediated cancer
      therapy.

PMID- 17510431
TI  - Scavenger receptor-A negatively regulates antitumor immunity.
AB  - The scavenger receptor-A (SR-A), originally recognized by its ability to
      internalize modified lipoproteins, has largely been studied in relation to
      atherosclerosis as well as innate immunity against pathogen infection. SR-A was
      recently shown to be a receptor on antigen-presenting cell for heat shock protein
      (HSP) and was implicated in the cross-presentation of HSP-chaperoned antigens.
      Here, we show that SR-A is not required for antitumor immunity generated by HSP
      based (e.g., grp170) vaccine approaches in vivo. The lack of SR-A significantly
      enhances HSP- or lipopolysaccharide-mediated vaccine activities against poorly
      immunogenic tumors, indicating that SR-A is able to attenuate immunostimulatory
      effects of adjuvants or "danger" molecules. The improved antitumor response in SR
      A knockout mice is correlated with an increased antigen-specific T-cell response.
      Moreover, SR-A-deficient dendritic cells are more responsive to inflammatory
      stimuli and display a more effective antigen-presenting capability compared with
      wild-type cells. This is the first report illustrating that SR-A negatively
      regulates antigen-specific antitumor immunity, which has important clinical
      implications in vaccine design for cancer immunotherapy.

PMID- 17510432
TI  - Chimeric NKG2D receptor-bearing T cells as immunotherapy for ovarian cancer.
AB  - Despite advancements in the treatment of ovarian cancer, this disease continues
      to be a leading cause of cancer death in women. Adoptive transfer of tumor
      reactive T cells is a promising antitumor therapy for many cancers. We designed a
      chimeric receptor linking NKG2D, a natural killer (NK) cell-activating receptor,
      to the CD3zeta chain of the T-cell receptor to target ovarian tumor cells.
      Engagement of chimeric NKG2D receptors (chNKG2D) with ligands for NKG2D, which
      are commonly expressed on tumor cells, leads to T-cell secretion of
      proinflammatory cytokines and tumor cytotoxicity. In this study, we show that
      >80% of primary human ovarian cancer samples expressed ligands for NKG2D on the
      cell surface. The tumor samples expressed MHC class I-related protein A, MICB,
      and UL-16 binding proteins 1 and 3. ChNKG2D-expressing T cells lysed ovarian
      cancer cell lines. We show that T cells from ovarian cancer patients that express
      chNKG2D secreted proinflammatory cytokines when cultured with autologous tumor
      cells. In addition, we show that chNKG2D T cells can be used therapeutically in a
      murine model of ovarian cancer. These data indicate that treatment with chNKG2D
      expressing T cells is a potential immunotherapy for ovarian cancer.

PMID- 17510433
TI  - Extralymphatic tumors prepare draining lymph nodes to invasion via a T-cell cross
      tolerance process.
AB  - Metastases often develop in lymphoid organs. However, the immunologic mechanism
      allowing such invasion is not known because these organs are considered to be
      hostile to tumor cells. Here, we analyzed the interactions between tumor cells
      and CD8(+) T cells in such lymphoid organs. Tumor cells implanted into lymph
      nodes were able to induce tumor-specific cytotoxic CD8(+) T-cell responses,
      conducting to tumor rejection, in contrast to primary extralymphatic tumors
      rapidly anergizing T cells in draining lymph nodes (DLN) via a cross-presentation
      process. This abortive CD8(+) T-cell response to extralymphatic tumor is
      independent of the subcellular localization of antigen in tumor cells and is
      consistent with a lack of CD4(+) T-cell help. Notably, this anergy was potent
      enough to allow successful DLN implantation of tumor cells. Such distant cross
      tolerization of tumor-specific CD8(+) T cells may be a determinant permissive
      event leading to invasion of DLN. In this situation, metastatic tumor cells do
      not need to down-regulate their immunogenicity to spread.

PMID- 17510434
TI  - Novel estrogen receptor-alpha binding sites and estradiol target genes identified
      by chromatin immunoprecipitation cloning in breast cancer.
AB  - Estrogen receptor-alpha (ERalpha) and its ligand estradiol play critical roles in
      breast cancer growth and are important therapeutic targets for this disease.
      Using chromatin immunoprecipitation (ChIP)-on-chip, ligand-bound ERalpha was
      recently found to function as a master transcriptional regulator via binding to
      many cis-acting sites genome-wide. Here, we used an alternative technology (ChIP
      cloning) and identified 94 ERalpha target loci in breast cancer cells. The
      ERalpha-binding sites contained both classic estrogen response elements and
      nonclassic binding sequences, showed specific transcriptional activity in
      reporter gene assay, and interacted with the key transcriptional regulators,
      including RNA polymerase II and nuclear receptor coactivator-3. The great
      majority of the binding sites were located in either introns or far distant to
      coding regions of genes. Forty-three percent of the genes that lie within 50 kb
      to an ERalpha-binding site were regulated by estradiol. Most of these genes are
      novel estradiol targets encoding receptors, signaling messengers, and ion
      binders/transporters. mRNA profiling in estradiol-treated breast cancer cell
      lines and tissues revealed that these genes are highly ERalpha responsive both in
      vitro and in vivo. Among estradiol-induced genes, Wnt11 was found to increase
      cell survival by significantly reducing apoptosis in breast cancer cells. Taken
      together, we showed novel genomic binding sites of ERalpha that regulate a novel
      set of genes in response to estradiol in breast cancer. Our findings suggest that
      at least a subset of these genes, including Wnt11, may play important in vivo and
      in vitro biological roles in breast cancer.

PMID- 17510435
TI  - SOCS1 silencing enhances antitumor activity of type I IFNs by regulating
      apoptosis in neuroendocrine tumor cells.
AB  - IFN-alpha is commonly used for biotherapy of neuroendocrine carcinomas. However,
      its antitumor efficacy is often limited due to IFN resistance. In this study, we
      evaluate the role of suppressor of cytokine signaling protein 1 (SOCS1) in
      modulating the effects of type I IFNs (IFN-alpha and IFN-beta) in human
      neuroendocrine BON1 and CM tumor cells. In both cell lines, type I IFNs activated
      signal transducers and activators of transcription (STAT) and significantly
      decreased cell viability. However, the effects of IFN-beta were significantly
      more pronounced than those of IFN-alpha and involved the induction of the
      intrinsic apoptotic pathway as shown by cleavage of caspase-8, Bid, and caspase
      9. Stable overexpression of SOCS1 completely abolished the apoptotic effects of
      both type I IFNs. In contrast, small interfering RNA (siRNA)-mediated silencing
      of SOCS1 resulted in strongly enhanced type I IFN signaling as shown by increased
      and prolonged STAT phosphorylation and stronger induction of apoptosis. Silencing
      of SOCS1 was associated with down-regulation of basal Bcl-2 and Bcl-xL and up
      regulation of basal Bak and Bax, suggesting that reduced SOCS1 expression might
      lower the threshold of susceptibility to type I IFN-mediated apoptosis by
      decreasing the ratio of antiapoptotic to proapoptotic molecules. In summary, our
      results indicate an important role of SOCS1 in IFN resistance of neuroendocrine
      tumor cells, mediated through negative regulation of type I IFN-induced Jak/STAT
      signaling. Knocking down SOCS1 by siRNA is a promising new approach to enhance
      the therapeutic potency of type I IFNs in neuroendocrine tumors.

PMID- 17510436
TI  - Intraprostatic androgens and androgen-regulated gene expression persist after
      testosterone suppression: therapeutic implications for castration-resistant
      prostate cancer.
AB  - Androgen deprivation therapy (ADT) remains the primary treatment for advanced
      prostate cancer. The efficacy of ADT has not been rigorously evaluated by
      demonstrating suppression of prostatic androgen activity at the target tissue and
      molecular level. We determined the efficacy and consistency of medical castration
      in suppressing prostatic androgen levels and androgen-regulated gene expression.
      Androgen levels and androgen-regulated gene expression (by microarray profiling,
      quantitative reverse transcription-PCR, and immunohistochemistry) were measured
      in prostate samples from a clinical trial of short-term castration (1 month)
      using the gonadotropin-releasing hormone antagonist, Acyline, versus placebo in
      healthy men. To assess the effects of long-term ADT, gene expression measurements
      were evaluated at baseline and after 3, 6, and 9 months of neoadjuvant ADT in
      prostatectomy samples from men with localized prostate cancer. Medical castration
      reduced tissue androgens by 75% and reduced the expression of several androgen
      regulated genes (NDRG1, FKBP5, and TMPRSS2). However, many androgen-responsive
      genes, including the androgen receptor (AR) and prostate-specific antigen (PSA),
      were not suppressed after short-term castration or after 9 months of neoadjuvant
      ADT. Significant heterogeneity in PSA and AR protein expression was observed in
      prostate cancer samples at each time point of ADT. Medical castration based on
      serum testosterone levels cannot be equated with androgen ablation in the
      prostate microenvironment. Standard androgen deprivation does not consistently
      suppress androgen-dependent gene expression. Suboptimal suppression of tumoral
      androgen activity may lead to adaptive cellular changes allowing prostate cancer
      cell survival in a low androgen environment. Optimal clinical efficacy will
      require testing of novel approaches targeting complete suppression of systemic
      and intracrine contributions to the prostatic androgen microenvironment.

PMID- 17510437
TI  - Immune mechanisms in non-Hodgkin lymphoma: joint effects of the TNF G308A and
      IL10 T3575A polymorphisms with non-Hodgkin lymphoma risk factors.
AB  - Two common single nucleotide polymorphisms in immunoregulatory genes (TNF G308A,
      rs1800629 and IL10 T3575A, rs1800890) have been recently reported as risk factors
      for non-Hodgkin lymphoma (NHL) in a large pooled analysis. We systematically
      investigated the effects of other established NHL risk factors in relation to the
      tumor necrosis factor (TNF) G308A or interleukin 10 (IL10) T3575A genotypes. We
      calculated odds ratios (OR) and 95% confidence intervals (95% CI) from 1,172
      cases and 982 population-based controls in a U.S. multicenter study. We
      investigated NHL overall and two common subtypes [diffuse large B-cell lymphoma
      (DLBCL) and follicular lymphoma]. NHL risks were increased among those with both
      an autoimmune condition and the TNF G308A GA/AA (OR(NHL), 2.1; 95% CI, 1.0-4.2)
      or the IL10 T3575A TA/AA genotype (OR(NHL), 1.6; 95% CI, 0.9-2.6) compared with
      individuals without an autoimmune condition and with the common TNF G308A GG or
      IL10 T3575A TT genotype, respectively; results were similar for DLBCL and
      follicular lymphoma. We found that elevated DLBCL risk associated with last-born
      status was more pronounced among those with TNF G308A GA/AA (OR(DLBCL), 2.7; 95%
      CI, 1.1-6.4) or IL10 T3575A TA/AA (OR(DLBCL), 2.9; 95% CI, 1.6-5.2). Similarly,
      elevated DLBCL risk associated with obesity (body mass index, > or = 35 versus
      <25 kg/m(2)) was observed only among those with TNF G308A GA/AA (OR(DLBCL), 2.5;
      95% CI, 1.1-5.7) or IL10 T3575A TA/AA genotypes (OR(DLBCL), 2.0; 95% CI, 1.1
      3.5). These exploratory results require replication but provide evidence that
      autoimmune conditions, late birth order, and obesity act partly through a common
      inflammatory pathway, posing a greater risk to individuals with variant TNF and
      IL10 genotypes than those with wild-type alleles.

PMID- 17510438
TI  - Anti-VEGFR-3 therapy and lymph node metastasis [corrected].

PMID- 17510441
TI  - How reliable are BRCA1/2 mutation estimates?

PMID- 17510442
TI  - Inhibition of antitumor immunity by B cells.

PMID- 17510444
TI  - Poststroke care: chronicles of a neglected battle.

PMID- 17510445
TI  - Brain microbleeds and cognitive function.

PMID- 17510446
TI  - Hypertension and cerebral blood flow: implications for the development of
      vascular cognitive impairment in the elderly.

PMID- 17510447
TI  - Toll-like receptor polymorphisms and carotid artery intima-media thickness.

PMID- 17510448
TI  - Ximelagatran versus warfarin in the prevention of atrial fibrillation-related
      stroke: both sides of the story.

PMID- 17510449
TI  - Carotid artery stenting: verdict still pending.

PMID- 17510450
TI  - rFVII for pediatric acute intracranial hemorrhage.

PMID- 17510451
TI  - Asymmetric dimethylarginine and hypertension in cerebral small vessel disease.

PMID- 17510452
TI  - Impact of anticoagulation on poststroke mortality in ischemic stroke patients
      with atrial fibrillation.

PMID- 17510453
TI  - Readmission and death after hospitalization for acute ischemic stroke: 5-year
      follow-up in the medicare population.
AB  - BACKGROUND AND PURPOSE: Stroke is a leading cause of hospital admission among the
      elderly. Although studies have examined subsequent vascular outcomes, limited
      data are available regarding the full burden of hospital readmission after
      stroke. We sought to determine the rates of hospital readmissions and mortality
      and the reasons for readmission over a 5-year period after stroke. METHODS: This
      retrospective observational cohort study included Medicare beneficiaries aged >65
      years who survived hospitalization for an acute ischemic stroke (International
      Classification of Diseases, Ninth Revision, Clinical Modification codes 434 and
      436) and who were discharged from Connecticut acute care hospitals in 1995. This
      population was followed from discharge in 1995 through 2000 using part A Medicare
      claims and Social Security Administration mortality data. The primary outcome was
      hospital readmission and mortality and readmission diagnosis. RESULTS: Among 2603
      patients discharged alive, more than half had died or been readmitted at least
      once during the first year after discharge (1388/2603, 53.3%), and <15% survived
      admission-free for 5 years (372/2603, 14.3%). The reasons for hospital
      readmission varied over time, with stroke remaining a leading cause for
      readmission (3.9 to 6.1% of patients annually). Acute myocardial infarction
      accounted for a comparable number of readmissions (4.2 to 6.0% of patients
      annually). The most common diagnostic category associated with readmission,
      however, was pneumonia or respiratory illnesses, with an annual readmission rate
      between 8.2% and 9.0% throughout the first 5 years after stroke. CONCLUSIONS: Few
      stroke patients survive for 5 years without a hospital readmission. Between the
      acute care setting and readmission to the hospital, a window of opportunity may
      exist for interventions, beyond prevention of recurrent vascular events alone, to
      reduce the huge public health burden of poststroke morbidity.

PMID- 17510454
TI  - Neurocognitive outcomes are not improved by 17beta-estradiol in postmenopausal
      women undergoing cardiac surgery.
AB  - BACKGROUND AND PURPOSE: Neurocognitive dysfunction is an important source of
      patient morbidity and mortality after cardiac surgery that may disproportionately
      affect postmenopausal women. 17beta-Estradiol limits the extent of ischemic
      neuronal injury in a variety of experimental models. The purpose of this study
      was to evaluate whether perioperative administration of 17beta-estradiol to
      postmenopausal women reduces the frequency of neurocognitive dysfunction after
      cardiac surgery. METHODS: One hundred seventy-four postmenopausal women not on
      estrogen replacement therapy who were undergoing primary coronary artery bypass
      graft surgery and/or valve surgery with cardiopulmonary bypass were prospectively
      randomized to receive in a double-blinded manner either 17beta-estradiol or
      placebo beginning the day before surgery and continuing for 5 days
      postoperatively. The patients were evaluated before and after surgery with the
      National Institutes of Health Stroke Scale and a psychometric test battery.
      RESULTS: There were no differences in the frequency of neurocognitive dysfunction
      (primary outcome) between patients randomized to perioperative 17beta-estradiol
      (n=86) and those randomized to placebo (n=88) 4 to 6 weeks after surgery (17beta
      estradiol, 22.4% versus placebo, 21.4%, P=0.45). The mean scores on tests of
      psychomotor speed were worse in women in the 17beta-estradiol group than in the
      placebo group at the 4- to 6-week (P=0.005) postoperative testing sessions.
      CONCLUSIONS: Perioperative treatment with 17beta-estradiol did not result in
      improved neurocognitive outcomes in postmenopausal women undergoing cardiac
      surgery.

PMID- 17510455
TI  - Questions on the first consensus document of the ICCS-SPREAD Joint Committee on
      Carotid Artery Stenting.

PMID- 17510457
TI  - Clinical significance of microbleeds in subcortical vascular dementia.
AB  - BACKGROUND AND PURPOSE: Despite many studies investigating the association
      between the ischemic changes and cognitive impairment in subcortical vascular
      dementia (SVaD), few studies correlated cognitive impairment with microbleeds
      (MBs) frequently seen in SVaD. METHODS: Participants consisted of 86 patients
      with SVaD who fulfilled the criteria proposed by Erkinjuntti et al. RESULTS: MBs
      occurred in 73 of 86 (84.9%) patients with SVaD. MBs were most commonly
      distributed in the cortex, and the cortical MBs were most pronounced in the
      temporoparietal area. A multiple regression showed that the number of cerebral MB
      was an independent predictor of cognitive impairment in multiple domains and the
      severity of dementia even after controlling confounding factors such as age,
      education, ischemic severity, and number of lacunes. CONCLUSIONS: These results
      indicate that cerebral MB is one of the important factors that cause cognitive
      impairments in SVaD.

PMID- 17510456
TI  - Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor
      recovery and stimulates neurogenesis.
AB  - BACKGROUND AND PURPOSE: The discovery of spontaneous neuronal replacement in the
      adult brain has shifted experimental stroke therapies toward a combined approach
      of preventing neuronal cell death and inducing neuronal plasticity. Brain-derived
      neurotrophic factor (BDNF) was shown to induce antiapoptotic mechanisms after
      stroke and to reduce infarct size and secondary neuronal cell death. Moreover, in
      intact animals, BDNF is a potent stimulator of adult neurogenesis. METHODS: The
      current study analyzed the effects of BDNF on induction of neuronal progenitor
      cell migration and sensorimotor recovery after cortical photothrombotic stroke.
      RESULTS: Daily intravenous bolus applications of BDNF during the first 5 days
      after stroke resulted in significantly improved sensorimotor scores up to 6
      weeks. At the structural level, BDNF significantly increased neurogenesis in the
      dentate gyrus and enhanced migration of subventricular zone progenitor cells to
      the nearby striatum of the ischemic hemisphere. BDNF treatment could not,
      however, further stimulate progenitor cell recruitment to the cortex.
      CONCLUSIONS: These findings consolidate the role of BDNF as a modulator of
      neurogenesis in the brain and as an enhancer of long-term functional neurological
      outcome after cerebral ischemia.

PMID- 17510458
TI  - Longitudinal changes in cerebral blood flow in the older hypertensive brain.
AB  - BACKGROUND AND PURPOSE: Changes in patterns of regional cerebral blood flow
      (rCBF) were assessed over a period of 6 years in 14 treated hypertensive
      participants (HTNs) and 14 age-matched healthy older participants (healthy
      controls [HCs]) in the Baltimore Longitudinal Study of Aging. METHODS: Resting
      state PET scans collected at years 1, 3, 5, and 7 were used to determine
      differences in longitudinal patterns of rCBF change in HTNs relative to HCs.
      Pulse pressure, arterial pressure, systolic/diastolic blood pressure, and
      hypertension duration were also correlated with patterns of rCBF change in the
      HTN group. RESULTS: Relative to HCs, the HTN group shows greater rCBF decreases
      in prefrontal, anterior cingulate, and occipital areas over time, suggesting that
      these regions are more susceptible to hypertension-related dysfunction with
      advancing age. The HTN group also fails to show preservation of function over
      time in motor regions and in the temporal cortex and hippocampus as observed in
      HC. Although pulse pressure, mean arterial pressure, and systolic and diastolic
      pressure all correlate similarly with longitudinal rCBF changes, increased
      duration of hypertension is associated with decreased rCBF in prefrontal and
      anterior cingulate areas of functional vulnerability observed in the HTN group.
      CONCLUSIONS: These results show that hypertension significantly affects resting
      brain function in older individuals and suggest that duration of hypertension
      contributes significantly to the patterns of change over time.

PMID- 17510459
TI  - Direct correlation between ischemic injury and extracellular glycine
      concentration in mice with genetically altered activities of the glycine cleavage
      multienzyme system.
AB  - BACKGROUND AND PURPOSE: Ischemia elicits the rapid release of various amino acid
      neurotransmitters. A glutamate surge activates N-methyl-d-aspartate (NMDA)
      glutamate receptors, triggering deleterious processes in neurons. Although
      glycine is a coagonist of the NMDA receptor, the effect of extracellular glycine
      concentration on ischemic injury remains controversial. To approach this issue,
      we examined ischemic injury in mice with genetically altered activities of the
      glycine cleavage multienzyme system (GCS), which plays a fundamental role in
      maintaining extracellular glycine concentration. METHODS: A mouse line with
      increased GCS activity (340% of C57BL/6 control mice) was generated by transgenic
      expression of glycine decarboxylase, a key GCS component (high-GCS mice). Another
      mouse line with reduced GCS activity (29% of controls) was established by
      transgenic expression of a dominant-negative mutant of glycine decarboxylase (low
      GCS mice). We examined neuronal injury after transient occlusion of the middle
      cerebral artery in these mice by measuring extracellular amino acid
      concentrations in microdialysates. RESULTS: High-GCS and low-GCS mice had
      significantly lower and higher basal concentrations of extracellular glycine than
      did controls, respectively. In low-GCS mice, the extracellular glycine
      concentration reached 2-fold of control levels during ischemia, and infarct
      volume was significantly increased by 69% with respect to controls. In contrast,
      high-GCS mice had a significantly smaller infarct volume (by 21%). No significant
      difference was observed in extracellular glutamate concentrations throughout the
      experiments. An antagonist for the NMDA glycine site, SM-31900, attenuated
      infarct size, suggesting that glycine operated via the NMDA receptor.
      CONCLUSIONS: There is a direct correlation between ischemic injury and
      extracellular glycine concentration maintained by the GCS.

PMID- 17510460
TI  - Combined carotid endarterectomy and coronary artery bypass: a still-feasible
      procedure?

PMID- 17510461
TI  - Improvements in speed-based gait classifications are meaningful.
AB  - BACKGROUND AND PURPOSE: Gait velocity is a powerful indicator of function and
      prognosis after stroke. Gait velocity can be stratified into clinically
      meaningful functional ambulation classes, such as household ambulation (<0.4
      m/s), limited community ambulation (0.4 to 0.8 m/s), and full community
      ambulation (>0.8 m/s). The purpose of the current study was to determine whether
      changes in velocity-based community ambulation classification were related to
      clinically meaningful changes in stroke-related function and quality of life.
      METHODS: In subacute stroke survivors with mild to moderate deficits who
      participated in a randomized clinical trial of stroke rehabilitation and had a
      baseline gait velocity of 0.8 m/s or less, we assessed the effect of success
      versus failure to achieve a transition to the next class on function and quality
      of life according to domains of the Stroke Impact Scale (SIS). RESULTS: Of 64
      eligible participants, 19 were initially household ambulators, and 12 of them
      (68%) transitioned to limited community ambulation, whereas of 45 initially
      limited community ambulators, 17 (38%) became full community ambulators. Function
      and quality-of-life SIS scores after treatment were significantly higher among
      survivors who achieved a favorable transition compared with those who did not.
      Among household ambulators, those who transitioned to limited or full community
      ambulation had significantly better SIS scores in mobility (P=0.0299) and
      participation (P=0.0277). Among limited community ambulators, those who achieved
      the transition to full community ambulatory status had significantly better
      scores in SIS participation (P=0.0085). CONCLUSIONS: A gait velocity gain that
      results in a transition to a higher class of ambulation results in better
      function and quality of life, especially for household ambulators. Household
      ambulators possibly had more severe stroke deficits, reducing the risk of
      "ceiling" effects in SIS-measured activities of daily living and instrumental
      activities of daily living. Outcome assessment based on transitions within a
      mobility classification scheme that is rooted in gait velocity yields potentially
      meaningful indicators of clinical benefit. Outcomes should be selected that are
      clinically meaningful for all levels of severity.

PMID- 17510462
TI  - Genetic deletion of pregnancy-associated plasma protein-A is associated with
      resistance to atherosclerotic lesion development in apolipoprotein E-deficient
      mice challenged with a high-fat diet.
AB  - Pregnancy-associated plasma protein-A (PAPP-A), a metalloproteinase in the
      insulin-like growth factor (IGF) system, is markedly upregulated in human
      atherosclerotic plaque. To determine whether PAPP-A plays an active role in the
      development of atherosclerosis, we crossed mice lacking apolipoprotein E (ApoE)
      with PAPP-A-deficient mice, generating ApoE knock-out (KO), PAPP-A KO, wild-type
      (WT/WT), and ApoE/PAPP-A double KO (KO/KO) mice. These mice were fed a high-fat
      diet starting at 7 weeks of age. Total serum cholesterol levels were elevated
      similarly in the ApoE KO and KO/KO mice and were 10-fold higher than in the WT/WT
      and PAPP-A KO mice. WT/WT and PAPP-A KO mice showed little or no lesion
      development even after 20 weeks of diet. ApoE KO mice had a progressive increase
      in aortic lesion area over 20 weeks of diet. In comparison, lesion area was
      reduced 60% to 80% in KO/KO mice. Lesions of ApoE KO aortas had 8- to 20-fold
      increases in PAPP-A, IGFBP-4, and IGF-I mRNA levels compared with nonlesional
      areas, whereas IGF-I receptor levels were equivalent--conditions for enhanced
      lesional IGF activity. Consistent with this, an in vivo marker of IGF-I receptor
      mediated action was increased 10-fold in lesions from ApoE KO compared with KO/KO
      aortas. These data indicate that PAPP-A plays a critical role in lesion
      development in a mouse model of atherosclerosis, at least in part, through
      amplification of local IGF-I bioavailability.

PMID- 17510463
TI  - Serum adipocyte fatty acid-binding protein levels were independently associated
      with carotid atherosclerosis.
AB  - OBJECTIVE: Adipocyte fatty acid-binding protein (A-FABP) has been shown to be an
      important player in atherosclerosis in animal models. However, the clinical
      relevance of these findings is still unknown. This study aims to examine the
      relationship between serum A-FABP level and carotid intima-media thickness (IMT),
      an indicator of atherosclerosis in humans. METHODS AND RESULTS: The study cohort
      included 479 Chinese subjects who underwent carotid IMT measurement. Serum A-FABP
      levels were determined by enzyme-linked immunosorbent assays. Serum A-FABP levels
      positively correlated with carotid IMT in both men (r=0.211, P=0.001) and women
      (r=0.435, P<0.001). In women, but not in men, the presence of plaques was
      associated with significantly higher serum A-FABP levels (P<0.001 versus women
      without plaques). Stepwise multiple regression analysis showed that serum A-FABP
      level was independently associated with carotid IMT in women (P=0.034), together
      with age and hypertension (both P<0.001). CONCLUSIONS: A-FABP is an independent
      determinant of carotid atherosclerosis in Chinese women, but not in men. This
      gender difference may be attributed to the lower serum A-FABP levels in men, and
      the effect of other risk factors, such as smoking, among our male participants.
      Our results have provided clinical evidence supporting the role of A-FABP in the
      development of atherosclerosis.

PMID- 17510464
TI  - Vascular responses to drug eluting stents: importance of delayed healing.
AB  - Polymer-based sirolimus- (Cypher) and paclitaxel-eluting (Taxus) drug eluting
      stents have become the treatment of choice for patients with symptomatic coronary
      artery disease undergoing percutaneous coronary intervention (PCI). Although
      these stents reduce rates of restenosis compared with bare metal stents (BMS),
      late thrombosis, a life threatening complication, has emerged as a major safety
      concern. Our understanding of the pathophysiology of late DES thrombosis is
      derived from animal and human pathologic samples taken after implantation of
      these devices. These data indicate that both DES cause substantial impairment in
      arterial healing characterized by lack of complete reendothelialization and
      persistence of fibrin when compared with BMS. This delayed healing is the primary
      substrate underlying all cases of late DES thrombosis at autopsy. Several
      additional risk factors for late stent thrombosis such as penetration of necrotic
      core, malapposition, overlapping stent placement, excessive stent length, and
      bifurcation lesions represent additional barriers to healing and should be
      avoided if DES are to be used to minimize the risk of late thrombosis. Because
      the time course of complete healing with DES in man is unknown, the optimal
      duration of antiplatelet treatment remains to be determined.

PMID- 17510465
TI  - Activation of human platelets by misfolded proteins.
AB  - OBJECTIVE: Protein misfolding diseases result from the deposition of insoluble
      protein aggregates that often contain fibrils called amyloid. Amyloids are found
      in Alzheimer disease, atherosclerosis, diabetes mellitus, and systemic
      amyloidosis, which are diseases where platelet activation might be implicated.
      METHODS AND RESULTS: We induced amyloid properties in 6 unrelated proteins and
      found that all induced platelet aggregation in contrast to fresh controls.
      Amyloid-induced platelet aggregation was independent of thromboxane A2 formation
      and ADP secretion but enhanced by feedback stimulation through these pathways.
      Treatments that raised cAMP (iloprost), sequestered Ca2+ (BAPTA-AM) or prevented
      amyloid-platelet interaction (sRAGE, tissue-type plasminogen activator [tPA])
      induced almost complete inhibition. Modulation of the function of CD36 (CD36-/-
      mice), p38(MAPK) (SB203580), COX-1 (indomethacin), and glycoprotein Ib alpha (Nk
      protease, 6D1 antibody) induced approximately 50% inhibition. Interference with
      fibrinogen binding (RGDS) revealed a major contribution of alphaIIb beta3
      independent aggregation (agglutination). CONCLUSIONS: Protein misfolding
      resulting in the appearance of amyloid induces platelet aggregation. Amyloid
      activates platelets through 2 pathways: one is through CD36, p38(MAPK),
      thromboxane A2-mediated induction of aggregation; the other is through
      glycoprotein Ib alpha-mediated aggregation and agglutination. The platelet
      stimulating properties of amyloid might explain the enhanced platelet activation
      observed in many diseases accompanied by the appearance of misfolded proteins
      with amyloid.

PMID- 17510466
TI  - Minimal lipidation of pre-beta HDL by ABCA1 results in reduced ability to
      interact with ABCA1.
AB  - OBJECTIVES: The aim of this study was to determine the role of ATP binding
      cassette transporter A1 (ABCA1) on generation of different-sized nascent HDLs.
      METHODS AND RESULTS: HEK293 cells stably-transfected with ABCA1 (HEK293-ABCA1) or
      non-transfected (control) cells were incubated with lipid free 125I-apoA-I for 24
      hours. Incubation of apoA-I with HEK293-ABCA1 cells, but not control cells, led
      to the formation of heterogeneous-sized, pre-beta migrating nascent HDL
      subpopulations (pre-beta1 to -4) that varied in size (7.1 to 15.7 nm), lipid, and
      apoA-I content. Kinetic studies suggested that all subpopulations were formed
      simultaneously, with no evidence for a precursor-product relationship between
      smaller and larger-sized particles. When isolated nascent pre-beta HDLs (pre
      beta1 to -4) were added back to HEK293-ABCA1 cells, their ability to bind to
      ABCA1 and efflux lipid was severely compromised. Heat-denaturation of pre-beta1
      HDL resulted in partial recovery of ABCA1 binding, suggesting that initial
      interaction of apoA-I with ABCA1 results in a constrained conformation of apoA-I
      that decreases subsequent binding. CONCLUSIONS: Interaction of apoA-I with ABCA1
      results in the simultaneous generation of pre-beta HDLs of discrete size and
      chemical composition. These nascent particles are poor substrates for subsequent
      lipidation by ABCA1 and presumably require additional non-ABCA1-mediated
      lipidation for further maturation.

PMID- 17510467
TI  - Weight-related increases in hypertension, hypercholesterolemia, and diabetes risk
      in normal weight male and female runners.
AB  - BACKGROUND: Although 36% of US men and 42% of US women are of normal weight, the
      health implications of greater weight in ostensibly normal-weight individuals are
      seldom acknowledged. METHODS AND RESULTS: Self-reported physician-diagnosed
      incident diabetes, high cholesterol, and hypertension were compared with adult
      body mass index (BMI), and body circumferences in 29,139 male and 11,985 female
      nonsmoking runners followed prospectively for 7.7 and 7.4 years, respectively.
      Included among these were 20,731 men and 11,197 women who were of normal weight
      at baseline (BMI < 25 kg/m2). During follow-up, 2342 men (8.53%) and 499 women
      (4.26%) became hypertensive, 3330 men (12.2%) and 599 women (5.14%) were
      diagnosed with high cholesterol, and 197 men (0.68%) and 28 women (0.23%) became
      diabetic. Increasing BMI and waist circumference at baseline significantly
      increased the log odds for normal-weight men becoming hypertensive (P<0.0001),
      hypercholesterolemic (P<0.0001), and diabetic (P<0.02), and for normal-weight
      women becoming hypertensive (P=0.05). The log odds for being diagnosed with high
      cholesterol also increased with baseline BMI in normal-weight women (P<0.05).
      Relative to men with BMI < 20 kg/m2, the odds for being diagnosed with
      hypertension or high cholesterol increased by 45% (P=0.05) and 64% (P=0.002),
      respectively, for those with 20 < or = BMI < 22.5 kg/m2, and by 121% (P<0.0001)
      and 135% (P<0.0001), respectively, for those with 22.5 < or = BMI < 25 kg/m2. The
      odds for women with 22.5 < or = BMI < 25 kg/m2 developing hypertension or high
      cholesterol were 33% (P=0.02) and 29% (P=0.03) higher, respectively, than for
      women with 20 < or = BMI < 22.5 kg/m2, and 64% (P=0.0007) and 41% (P=0.008)
      higher, respectively, than women with BMI < 20 kg/m2. Relative to men and women
      with BMI < 22.5 kg/m2, the odds for developing diabetes during follow-up
      increased by 119% (P=0.009) and 116% (P=0.17), respectively, for those with 22.5
      < or = BMI < 25 kg/m2. CONCLUSIONS: Greater BMI and larger waist circumference
      increase the risks for hypertension, high cholesterol, and diabetes even among
      normal-weight nonsmoking runners, although overall risks remain relatively low
      vis-a-vis those for the overweight or obese.

PMID- 17510468
TI  - CYP26 inhibitor R115866 increases retinoid signaling in intimal smooth muscle
      cells.
AB  - OBJECTIVE: Intimal smooth muscle cells (SMCs) are dedifferentiated SMCs that have
      a powerful ability to proliferate and migrate. This cell-type is responsible for
      the development of intimal hyperplasia after vascular angioplasty. Retinoids,
      especially all-trans retinoid acid, are known to regulate many processes
      activated at sites of vascular injury, including modulation of SMC phenotype and
      inhibition of SMC proliferation. Intracellular levels of active retinoids are
      under firm control. A key enzyme is the all-trans retinoic acid-degrading enzyme
      cytochrome p450 isoform 26 (CYP26). Thus, an alternative approach to exogenous
      retinoid administration could be to increase the intracellular level of all-trans
      retinoic acid by blocking CYP26-mediated degradation of retinoids. METHODS AND
      RESULTS: Vascular intimal and medial SMCs expressed CYP26A1 and B1 mRNA. Although
      medial cells remained unaffected, treatment with the CYP26-inhibitor R115866
      significantly increased cellular levels of all-trans retinoic acid in intimal
      SMCs. The increased levels of all-trans retinoic acid induced retinoid-regulated
      genes and decreased mitogenesis. CONCLUSIONS: Blocking of the CYP26-mediated
      catabolism mimics the effects of exogenously administrated active retinoids on
      intimal SMCs. Therefore, CYP26-inhibitors offer a potential new therapeutic
      approach to vascular proliferative disorders.

PMID- 17510469
TI  - Apolipoprotein E interrupts interleukin-1beta signaling in vascular smooth muscle
      cells.
AB  - OBJECTIVES: Apolipoprotein E (apoE) exerts antiatherogenic effects but precise
      mechanisms remain unclear. We here investigated the effect of apoE on
      intracellular signaling by interleukin-1beta (IL-1beta), a proinflammatory
      cytokine present in atherosclerotic lesions. METHODS AND RESULTS: IL-1beta
      induced expression and activation of inducible nitric oxide synthase and
      cyclooxygenase-2 were inhibited by apoE in vascular smooth muscle cells (VSMCs).
      These inhibitory effects were linked to the suppression of both NF-kappaB and
      activating protein-1 (AP-1) transactivation, suggesting that the interruption of
      IL-1beta signaling occurs upstream of transcription factors. Studies in VSMCs
      overexpressing IL-1beta signaling intermediates revealed that NF-kappaB
      transactivation was inhibited by apoE in MyD88- and IRAK1- but not in TRAF6
      transfected cells. Furthermore, apoE prevented IRAK1 phosphorylation and IRAK1
      TRAF6 but not MyD88-IRAK1 complex formation. Inhibitory effects of apoE on IL
      1beta signaling were abolished after silencing LDL receptor-related protein-1
      (LRP1) expression with siRNA. In addition, inhibitors of adenylyl cyclase and
      protein kinase A (PKA) restored IL-1beta signaling in apoE-treated VSMCs, whereas
      apoE stimulated PKA activity. ApoE inhibited VSMC activation in response to IL-18
      but not to tumor necrosis factor-alpha or polyinosinic:polycytidylic acid.
      CONCLUSION: ApoE targets IRAK-1 activation and thereby interrupts IL-1beta and IL
      18 signaling in VSMCs. This antiinflammatory effect represents a novel
      antiatherogenic activity of apoE.

PMID- 17510470
TI  - Grassroots advocacy campaign for HIV/AIDS prevention: lessons from the field.
AB  - There are many guides written for developing strategies and tactics related to
      advocacy, and many pages of text are devoted to developing advocacy plans. Less
      well described is the context within which grassroots advocacy campaigns can be
      successful. This article describes a successful campaign to establish a needle
      exchange program (NEP) in Guilford County, North Carolina. The authors briefly
      describe NEPs in general, the history of NEPs in North Carolina, the mission of
      the North Carolina Harm Reduction Coalition (NCHRC), and why this approach was
      considered particularly important for Guilford County. Then the context of the
      successful adoption of an NEP in Guilford County and the progress to make it
      legal will be examined, including describing the specific advocacy activities
      facilitated by members of NCHRC. The article concludes with a discussion of
      lessons learned that may be applicable to other grassroots advocacy initiatives.

PMID- 17510471
TI  - Strengthening community leadership: evaluation findings from the california
      healthy cities and communities program.
AB  - Collaborative approaches to community health improvement such as healthy cities
      and communities have the potential to strengthen community capacity through
      leadership development. The healthy cities and communities process orients
      existing local leadership to new community problem-solving strategies and draws
      out leadership abilities among residents not previously engaged in civic life. In
      an evaluation of the California Healthy Cities and Communities (CHCC) Program,
      leadership development was one of several outcomes assessed at the civic
      participation level of the social ecology. Data collection methods included focus
      groups and surveys, semistructured interviews with coordinators and community
      leaders, and review of program documents. Findings suggest that the CHCC program
      enhanced capacity by expanding new leadership opportunities through coalition
      participation, program implementation, and civic leadership roles related to spin
      off organizations and broader collaborative structures. Communities in rural
      regions were particularly successful in achieving significant leadership
      outcomes.

PMID- 17510472
TI  - Epidemiology of giant cell arteritis in an Arab population: a 22-year study.

PMID- 17510473
TI  - Results of high-density silicone oil as a tamponade agent in macular hole retinal
      detachment in patients with high myopia.

PMID- 17510474
TI  - Photodynamic therapy in the anti-VEGF era.

PMID- 17510475
TI  - Prevalence of glaucoma in rural Myanmar: the Meiktila Eye Study.
AB  - AIM: To determine the prevalence of glaucoma in the Meiktila district of central,
      rural Myanmar. METHODS: A cross-sectional, population-based survey of inhabitants
      > or =40 years of age from villages in Meiktila district, Myanmar, was performed;
      2481 eligible participants were identified and 2076 participated in the study.
      The ophthalmic examination included Snellen visual acuity, slit-lamp examination,
      tonometry, gonioscopy, dilated stereoscopic fundus examination and full-threshold
      perimetry. Glaucoma was classified into clinical subtypes and categorised into
      three levels according to diagnostic evidence. RESULTS: Glaucoma was diagnosed in
      1997 (80.5%) participants. The prevalence of glaucoma of any category in at least
      one eye was 4.9% (95% CI 4.1 to 5.7; n = 101). The overall prevalence of primary
      angle-closure glaucoma (PACG) was 2.5% (95% CI 1.5 to 3.5) and of primary open
      angle glaucoma (POAG) was 2.0% (95% CI 0.9 to 3.1). PACG accounted for 84% of all
      blindness due to glaucoma, with the majority due to acute angle-closure glaucoma
      (AACG). CONCLUSION: The prevalence of glaucoma in the population aged > or =40
      years in rural, central Myanmar was 4.9%. The ratio of PACG to POAG was
      approximately 1.25:1. PACG has a high visual morbidity and AACG is visually
      devastating in this community. Screening programmes should be directed at PACG,
      and further study of the underlying mechanisms of PACG is needed in this
      population.

PMID- 17510477
TI  - Postoperative endophthalmitis associated with sutured versus unsutured clear
      corneal cataract incisions.
AB  - AIM: To compare the incidence of postoperative endophthalmitis in clear corneal
      cataract surgeries performed with and without suture closure, antibiotics and
      povidone iodine. SETTING: Ambulatory surgery facility. METHODS: In a
      retrospective, consecutive case-series study, we reviewed the incidence of
      endophthalmitis in 815 consecutive eyes that underwent cataract surgery by a
      single surgeon over a 5-year period (379 unsutured and 436 sutured, 294 without
      and 521 with antibiotic drops in the immediate postoperative period, and 247
      without and 568 with povidone iodine before patching). RESULTS: There were five
      cases of culture-positive postoperative endophthalmitis in the unsutured group
      and none in the sutured group (p = 0.022). Although patients in these two groups
      received routine preoperative antibiotic and povidone-iodine drops, those in whom
      antibiotic eye drops were not initiated until the day after surgery (p = 0.006)
      and those who did not receive 5% povidone-iodine drops immediately after wound
      closure (p = 0.031), had a higher incidence of endophthalmitis. CONCLUSION:
      Results suggest that by suturing the corneal incisions, by initiating antibiotic
      eye drops within the first 24 h of surgery and by instilling povidone-iodine
      drops after closure, the incidence of endophthalmitis after cataract surgery
      could possibly be reduced.

PMID- 17510478
TI  - The Halifax disaster (1917): eye injuries and their care.
AB  - Explosions, man-made and accidental, continue to require improved emergency
      medical responses. In the 1917 Halifax Explosion, an inordinate number of
      penetrating eye injuries occurred. A review of their treatment provides insight
      into a traumatic event with unique ophthalmological importance. Archived personal
      and government documents relating to the Halifax Explosion were reviewed at the
      Public Archives of Nova Scotia, Canada, along with a review of current
      literature. Twelve ophthalmologists treated 592 people with eye injuries and
      performed 249 enucleations. Sixteen people had both eyes enucleated. Most of the
      eye injuries were caused by shards of shattered glass. A Blind Relief Fund was
      established to help treat and rehabilitate the visually impaired. The injured
      were given pensions through the Canadian National Institute for the Blind,
      Toronto, Ontario, Canada, which continue to this day. Sympathetic ophthalmia was
      the feared complication for penetrating eye injuries and a common indication for
      enucleation in 1917. Even so, the severity and the overwhelming number of eye
      injuries sustained during the Halifax Explosion made it impossible for lengthy
      eye-saving procedures to be performed. Enucleation was often the only option.

PMID- 17510480
TI  - Retinal seeding from anterior segment coccidioidomycosis after vitrectomy.

PMID- 17510479
TI  - High beta-trace protein concentration in the fluid of an orbital cyst associated
      with bilateral colobomatous microphthalmos.

PMID- 17510481
TI  - Optical coherence tomography can monitor reversible nerve-fibre layer changes in
      a patient with ethambutol-induced optic neuropathy.

PMID- 17510482
TI  - Frequency of retinal macroaneurysms in adult Chinese: the Beijing Eye Study.

PMID- 17510483
TI  - Amniotic membrane-covered bio-onlays for treatment of ocular surface disease.

PMID- 17510484
TI  - Ocular myasthenia: a rare presentation with MuSK antibody and bilateral
      extraocular muscle atrophy.

PMID- 17510485
TI  - Abducens palsy and Sjogren's syndrome induced by pegylated interferon therapy.

PMID- 17510486
TI  - Botulinum toxin injection causing lateral rectus palsy.

PMID- 17510487
TI  - Secondary paracentral retinal holes after removal of the internal limiting
      membrane.

PMID- 17510488
TI  - Overestimation of uncorrected refractive error in Singapore teenagers.

PMID- 17510489
TI  - King Ludd meets virtual reality.

PMID- 17510490
TI  - Segmental and complementary expression of L-serine biosynthetic enzyme 3
      phosphoglycerate dehydrogenase and neutral amino acid transporter ASCT1 in the
      mouse kidney.
AB  - 3-Phosphoglycerate dehydrogenase (Phgdh) is the initial step enzyme in the
      phosphorylated pathway of L-serine biosynthesis. We have previously revealed in
      the brain that Phgdh is preferentially expressed in glial cells, but not in
      neurons, and that glia-borne L-serine exerts strong neurotrophic actions to
      neuronal survive, differentiation, and development. To investigate whether such
      an L-serine-meditated intercellular relationship is constructed in peripheral
      organs and tissues, we examined the kidney, which is one of the organs with the
      highest expression of Phgdh mRNA in the body. We found that Phgdh was distributed
      highly in the renal papilla and inner layer of the outer zone and moderately in
      the cortex, whereas it was almost negative in the outer layer of the outer zone.
      This heterogeneous distribution was due to selective expression in distinct
      tubular segments, i.e., the Bowman's capsule, proximal tubule, and thin limbs of
      the Henle's loop. Interestingly, neutral amino acid transporter ASCT1, which
      preferentially transports alanine, serine, cysteine, and threonine, was
      selectively expressed in Phgdh-negative tubular segments, i.e., the distal tubule
      and collecting duct. Therefore, either Phgdh or ASCT1 is provided to each segment
      of renal tubules, suggesting that metabolic interplay mediated by L-serine
      biosynthesis and supply may exist in the kidney too.

PMID- 17510491
TI  - Potentiation of intestinal immunity by micellary mushroom extracts.
AB  - Mushroom (shiitake) extracts were dispersed with lecithin micelles to prepare
      superfine particles (0.05 to 0.2 microm in diameter) of beta-1,3-glucan
      (micellary mushroom extracts). When mice were fed with these micelles of beta
      glucan (0.75 mg/day/mouse, smaller amounts of beta-glucan), the number of
      lymphocytes yielded by the small intestine increased by up to 40%. More
      interestingly, the ratio of CD8alphabeta(+)TCRalphabeta(+)
      cells/CD8alphaalpha(+)TCRalphabeta(+) cells increased prominently. In parallel
      with this deviation in the distribution of lymphocyte subsets, tumor cytotoxicity
      against P815 cells and cytokine productions were also augmented. In other words,
      phylogenetically developed lymphocytes (CD8alphabeta(+), TCRalphabeta(+)) were
      much more effectively activated by the oral administration of micellary beta
      glucan. These results suggest that smaller amounts of micellary beta-glucan might
      be useful for the potentiation of intestinal immunity.

PMID- 17510492
TI  - Relationships between insulin release and taste.
AB  - Tasting sweet food elicits insulin release prior to increasing plasma glucose
      levels, known as cephalic phase insulin release (CPIR). The characteristic of
      CPIR is that plasma insulin secretion occurs before the rise of the plasma
      glucose level. In this experiment, we examined whether taste stimuli placed on
      the tongue could induce CPIR. We used female Wistar rats and five basic taste
      stimuli: sucrose (sweet), sodium chloride (salty), HCl (sour), quinine (bitter)
      or monosodium glutamate (umami). Rats reliably exhibited CPIR to sucrose. Sodium
      chloride, HCl, quinine, or monosodium glutamate did not elicit CPIR. The non
      nutritive sweetener saccharine elicited CPIR. However, starch, which is nutritive
      but non-sweet, did not elicit CPIR although rats showed a strong preference for
      starch which is a source of glucose. In addition, we studied whether CPIR was
      related to taste receptor cell activity. We carried out the experiment in rats
      with bilaterally cut chorda tympani nerves, one of the gustatory nerves. After
      sectioning, CPIR was not observed for sweet stimulation. From these results, we
      conclude that sweetness information conducted by thistaste nerve provides
      essential information for eliciting CPIR.

PMID- 17510493
TI  - Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol
      levels in healthy humans.
AB  - Dietary supplementation with an essential amino acid L-lysine has been shown to
      reduce chronic anxiety in humans with low dietary intake of L-lysine. A
      combination of L-lysine and L-arginine has been documented to normalize hormonal
      stress responses in humans with high trait anxiety. The present study was carried
      out in one hundred eight healthy Japanese adults. The aim of study was to find
      out whether a week-long oral treatment with L-lysine (2.64 g per day) and L
      arginine (2.64 g per day) reduces trait and stress-induced state anxiety and
      basal levels of stress hormones. We confirmed that, without regard to gender, the
      amino acid treatment significantly reduced both trait anxiety and state anxiety
      induced by cognitive stress battery. In addition, we found that the treatment
      with L-lysine and L-arginine decreased the basal levels of salivary cortisol and
      chromogranin-A (a salivary marker of the sympatho-adrenal system) in male
      subjects. These results of this double-blind, placebo controlled and randomized
      study confirm the previous findings in humans and animals and point to a
      combination of L-lysine and L-arginine as a potentially useful dietary
      intervention in otherwise healthy humans with high subjective levels of mental
      stress and anxiety.

PMID- 17510494
TI  - An inhaled inducible nitric oxide synthase inhibitor reduces damage of Candida
      induced acute lung injury.
AB  - Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS)
      aggravates acute lung injury (ALI) by producing peroxynitrite. We previously
      showed by immunostaining that the expression of iNOS was suppressed by inhalation
      of N(G)-nitro-L-arginine methyl ester in mice with Candida-induced ALI. This
      study tested the hypothesis that a novel iNOS inhibitor suppresses not only iNOS
      expression, but also iNOS messenger RNA (mRNA) production by interrupting a
      positive feedback loop at the time of NO production in Candida-induced ALI. Mice
      were pretreated by inhalation of saline or ONO-1714, a selective iNOS inhibitor,
      and were given an intravenous injection of Candida albicans to induce ALI. After
      inhalation of 1 mM aerosolized ONO-1714, the nitrite-nitrate concentration in
      bronchoalveolar lavage fluid (BALF) at 24 h was significantly lower than that
      after inhalation of saline. Tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) levels and neutrophils in BALF were decreased by
      inhalation of ONO-1714. Inhalation of ONO-1714 markedly suppressed nitrotyrosine
      production and inhibited the expression of iNOS mRNA as well as proteins in the
      lung. Survival was prolonged by inhalation of ONO-1714. We conclude that
      pretreatment with inhaled ONO-1714 suppresses the production of peroxinitrite and
      decreases oxidative stress associated with peroxinitrite in Candida-induced ALI.

PMID- 17510495
TI  - Effects of walking exercise on nocturia in the elderly.
AB  - We investigated whether nocturia in the elderly was improved by walking exercise,
      which involved walking rapidly for 30 min or more in the evening or night for 8
      weeks. A questionnaire related to micturition and exercise, blood pressure, body
      composition analysis, blood biochemistry tests, and urinalysis were performed
      before and after 8 weeks of exercise to investigate the effects of walking.
      Thirty men (71 years old on average) continued the walking exercise for long
      enough to undergo evaluation. The number of episodes of nocturia decreased
      significantly (p < 0.001) from 3.3 +/- 0.7 to 1.9 +/- 0.8 after 8 weeks of
      walking exercise. The daytime urinary frequency, blood pressure, body weight,
      body fat ratio, edema ratio, serum catecholamines, triglycerides, and total
      cholesterol were also decreased. After 8 weeks of exercise, 20 of the subjects
      (67%) stated that sleep was deeper than before exercise. Assessment of the
      overall improvement showed that excellent or good results were obtained in 18
      patients (60%). The main factor related to the influence of walking exercise on
      nocturia was that sleep became deeper, which increased the arousal threshold
      bladder volume. Walking exercise may also have a preventive effect on lifestyle
      related diseases.

PMID- 17510496
TI  - Effectiveness of proliferating tissues in combination with bovine-derived
      xenografts to intrabony defects of alveolar bone in dogs.
AB  - The aim of this study was to investigate the effect of proliferating tissue used
      in combination with bovine-derived xenograft (BDX) on the formation of new
      cementum and bone in dogs. Intrabony defects were treated with either BDX in
      conjunction with autogenous proliferating tissues (BDXplus-proliferating tissues:
      BDX-P group) or BDX alone (BDX-alone group). The control group received no BDX or
      proliferating tissues. The animals were sacrificed after 2, 4, and 8 weeks of the
      treatment, and tissues were histologically examined. Specimens from the control
      group were characterized by long junctional epithelium and little bone formation.
      The BDX-P group showed a statistically significant increase in new bone and
      cementum formation compared to the BDX-alone group (30.9% vs. 18.7, p < 0.01 and
      87.8% vs. 61.8, p < 0.01). The ratio of proliferating cell nuclear antigen (PCNA)
      positive cells in the newly formed connective tissue of the BDX-P group was
      significantly greater than that in the BDX-alone group. These findings suggest
      that the use of proliferating tissues in combination with BDX enhances new bone
      and cementum formation, offering potential as therapeutic material in periodontal
      regeneration.

PMID- 17510497
TI  - Effect of laughter on salivary endocrinological stress marker chromogranin A.
AB  - We investigated the effect of laughter on salivary endocrinological stress marker
      chromogranin A (CgA). In saliva samples collected from 11 healthy males before
      and after watching a comic film or a non-humorous control film, salivary CgA
      levels were determined by enzyme-linked immunosorbent assay (ELISA). Samples
      taken after watching the comic film showed increased levels of CgA. This tendency
      was more pronounced in individuals with lower initial levels of stress. The
      control samples showed no significant change in CgA levels. Stress score,
      subjectively evaluated using a visual analog scale, decreased significantly after
      watching the comic film. These findings suggest that, in addition to a stress
      relief effect, laughter can bring about feeling uplifted or fulfilled.

PMID- 17510498
TI  - Role of FoxO Proteins in Pancreatic beta Cells.
AB  - Forkhead transcription factors of the FoxO family have important roles in
      cellular proliferation, apoptosis, differentiation and stress resistance. FoxO
      proteins also play important roles in metabolism of complex organisms. FoxO1
      regulates glucose and lipid metabolism in liver, as well as preadipocyte,
      myoblast and vascular endothelial cell differentiation. In the hypothalamus, FoxO
      controls food intake. In this chapter, we review the role of FoxO in pancreatic
      beta cells. Pancreatic beta cells secrete insulin to maintain the plasma glucose
      levels in a strict physiological range. Defects of beta cell function cause
      diabetes. The expression pattern of FoxO1 during pancreatic organogenesis is
      similar to that of Pdx1, Nkx2.2 and Pax4, transcription factors known to be
      critical for beta cell development. FoxO1 is expressed in a subset of pancreatic
      duct cells, in which insulin and/or Pdx1 are occasionally expressed. FoxO1
      inhibits beta cell proliferation through suppression of Pdx1 by competing with
      FoxA2 and protects against beta cell failure induced by oxidative stress through
      NeuroD and MafA induction. Thus, a series of FoxO1 studies in pancreas suggested
      that FoxO1 plays important roles in pancreatic beta cell differentiation,
      neogenesis, proliferation and stress resistance. Genetic or pharmacological
      manipulation of FoxO can be used to prevent beta cell failure or aid in the
      differentiation of uncommitted endocrine progenitors into beta cells for
      transplantation.

PMID- 17510499
TI  - Avenues of communication between the brain and tissues/organs involved in energy
      homeostasis.
AB  - Obesity is a rapidly increasing public health concern worldwide as a major risk
      factor for numerous disorders, including diabetes, hypertension and heart
      disease. Despite remarkable advances in obesity research over the past 10 years,
      the molecular mechanisms underlying obesity are still not completely understood.
      To maintain systemic energy homeostasis, it is important that organs/tissues
      communicate metabolic information among each other. Obesity-related disorders can
      be thought of as resulting from dysregulation of this inter-tissue communication.
      This system has both afferent sensing components and efferent effecter limbs. The
      afferent signals consist of not only humoral factors, such as nutrients (glucose,
      fatty acids and amino acids) and adipocytokines (leptin, adiponectin and so on),
      but also autonomic afferent nerve systems. Both converge on brain centers, most
      importantly within the hypothalamus, where the signals are integrated, and the
      direction and magnitude of efferent responses are determined. The efferent
      elements of this physiological system include those regulating energy inputs and
      outputs, i.e. food intake and metabolic rates. In this review, we will summarize
      recent advances in research on metabolic information avenues to the brain, which
      are important for energy homeostasis.

PMID- 17510500
TI  - Increased Fructose 2,6-bisphosphate in peripheral blood mononuclear cells of
      patients with diabetes.
AB  - Fructose 2,6-bisphosphate (F2,6BP) is a powerful allosteric activator of 6
      phosphofructo-1-kinase, which is the rate-limiting enzyme for glycolysis.
      Mitogenic stimulation of lymphocytes is related to an enhanced rate of glucose
      utilization and F2,6BP mediated activation of glycolysis. To determine the effect
      of hyperglycemia on intracellular glycolysis of lymphocytes, we measured
      intracellular F2,6BP content in peripheral blood mononuclear cells obtained from
      patients with diabetes and normal subjects. A total of 62 subjects participated
      in the present study. Venous blood samples were collected and peripheral blood
      mononuclear cells were separated by Ficoll gradients. Intracellular F2,6BP levels
      in peripheral blood mononuclear cells from normal control subjects were
      significantly lower than age-matched diabetic subjects. We observed a significant
      positive correlation between intracellular F2,6BP levels and long term glycemic
      control, as assessed by HbA1c. These data suggest that hyperglycemia increases
      intracellular F2,6BP in immune cells. These findings may help to clarify the
      impaired function in immune cells in patients with diabetes.

PMID- 17510501
TI  - Association between estrogen receptor alpha (ESR1) gene polymorphisms and severe
      preeclampsia.
AB  - Associations have been reported between estrogen receptor alpha (ESR1) gene
      polymorphisms and various pathological conditions, including cardiovascular
      diseases. Our aim was to investigate whether two polymorphisms of the ESR1 gene
      (ESR1 c.454 -397T>C: PvuII restriction site and c.454 -351A>G: XbaI restriction
      site) are associated with preeclampsia. In a case-control study, we analyzed
      blood samples from 119 severely preeclamptic patients and 103 normotensive,
      healthy pregnant women using the polymerase chain reaction (PCR)-restriction
      fragment length polymorphism (RFLP) method. All of the women were Caucasian.
      There was no association between severe preeclampsia and the PvuII and XbaI ESR1
      gene polymorphisms separately. However, with the simultaneous carriage of both
      polymorphisms, the TT/AA genotype combination was significantly more frequent in
      severely preeclamptic patients than in healthy control subjects (24.4% vs. 9.7%,
      p=0.003), whereas the TT/AG combination was significantly less frequent in the
      severely preeclamptic group than in the control group (5.0% vs. 18.4%, p=0.002).
      According to the haplotype estimation, the homozygous T-A haplotype carriers had
      an increased risk of severe preeclampsia independent of maternal age,
      prepregnancy BMI, primiparity and smoking status (adjusted odds ratio [OR]: 4.36,
      95% confidence interval [CI]: 1.65-11.53). The GG genotype of the XbaI
      polymorphism was associated with a lower risk of fetal growth restriction in
      patients with severe preeclampsia (OR: 0.23, 95% CI: 0.07-0.73). In conclusion,
      the homozygous T-A haplotype carriers of ESR1 PvuII and XbaI polymorphisms showed
      an increased risk of severe preeclampsia. In addition, the GG genotype of the
      XbaI polymorphism decreased the risk of fetal growth restriction in severely
      preeclamptic patients.

PMID- 17510502
TI  - NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies the effects of
      alcohol consumption on risk for hypertension in middle-aged Japanese men.
AB  - NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met)
      polymorphism is associated with longevity in the Japanese population, and the ND2
      237Met genotype may exert antiatherogenic effects. To investigate whether ND2-237
      Leu/Met polymorphism is associated with risk of hypertension, we conducted a
      cross-sectional study of 398 Japanese male subjects. The frequency of
      hypertension was significantly higher in ND2-237Leu genotypic men than in ND2
      237Met genotypic men. On analysis of covariance, the interaction between ND2-237
      Leu/Met polymorphism and habitual drinking was significantly associated with both
      systolic blood pressure and diastolic blood pressure. Multiple logistic
      regression analysis revealed that the ND2-237Met genotype, particularly in
      younger subjects (age <60 years), had a lower odds ratio for hypertension than
      the ND2-237Leu genotype. Moreover, the association of ND2-237 Leu/Met
      polymorphism with hypertension may depend on the frequency of alcohol
      consumption. The odds ratio for hypertension was significantly higher in daily
      drinkers with ND2-237Leu when compared with non- or ex-drinkers with ND2-237Leu.
      However, the association between the ND2-237Met genotype and hypertension may not
      depend on the frequency of alcohol consumption. The present results suggest that
      ND2-237 Leu/Met polymorphism is associated with hypertension and that
      modification of hypertension risk is dependent on alcohol consumption in middle
      aged Japanese men.

PMID- 17510503
TI  - Relationship between radial and central arterial pulse wave and evaluation of
      central aortic pressure using the radial arterial pulse wave.
AB  - Since a decrease of central aortic pressure contributes to the prevention of
      cardiovascular events, simple measurement of not only brachial blood pressure but
      also central aortic pressure may be useful in the prevention and treatment of
      cardiovascular diseases. In this study, we simultaneously measured radial artery
      pulse waves non-invasively and ascending aortic pressure invasively, before and
      after the administration of nicorandil. We then compared changes in central
      aortic pressure and radial arterial blood pressure calibrated with brachial blood
      pressure in addition to calculating the augmentation index (AI) at the aorta and
      radial artery. After nicorandil administration, the reduction in maximal systolic
      blood pressure in the aorta (Deltaa-SBP) was -14+/-15 mmHg, significantly larger
      than that in early systolic pressure in the radial artery (Deltar-SBP) (-9+/-12
      mmHg). The reduction in late systolic blood pressure in the radial artery (Deltar
      SBP2) was -15+/-14 mmHg, significantly larger than Deltar-SBP, but not
      significantly different from Deltaa-SBP. There were significant relationships
      between Deltaa-SBP and Deltar-SBP (r=0.81, p<0.001), and between Deltaa-SBP and
      Deltar-SBP2 (r=0.91, p<0.001). The slope of the correlation regression line with
      Deltar-SBP2 (0.83) was larger and closer to 1 than that with Deltar-SBP (0.63),
      showing that the relationship was close to 1:1. Significant correlations were
      obtained between aortic AI (a-AI) and radial AI (r-AI) (before nicorandil
      administration: r=0.91, p<0.001; after administration: r=0.70, p<0.001). These
      data suggest that the measurement of radial artery pulse wave and observation of
      changes in the late systolic blood pressure in the radial artery (r-SBP2) in
      addition to the ordinary measurement of brachial blood pressure may enable a more
      accurate evaluation of changes in maximal systolic blood pressure in the aorta (a
      SBP).

PMID- 17510504
TI  - Relationship between visceral fat and cardiovascular disease risk factors: the
      Tanno and Sobetsu study.
AB  - We assessed the amount of visceral fat using ultrasonography (US) and studied its
      relationship to cardiovascular disease risk factors, particularly blood pressure.
      The subjects in the first study were 45 male and 61 female outpatients. We
      measured the visceral fat area (VFA) of each subject using abdominal CT and waist
      circumference (WC), and visceral fat distance (VFD) using US. The subjects in the
      second study were 353 male and 457 female inhabitants of a rural community, for
      whom VFD and WC were measured. We divided subjects into tertiles based on VFD and
      WC, and studied the relationship between each group and individual risk factors.
      In an analysis of outpatient subjects, the correlation coefficient between VFA
      and VFD was satisfactory: r=0.660 for men and r=0.643 for women. In the analysis
      of the rural subjects, the high VFD group had a significantly higher odds ratio
      than the low VFD group in high blood pressure (HBP) and hypertriglyceridemia
      (HTG) for men and in HBP, HTG and low high-density lipoprotein cholesterolemia
      (LHDL) for women. Moreover, adjusting VFD for body mass index revealed that, in
      comparison to WC, VFD was significantly related to risk factors. VFD was used as
      an independent variable in multiple regression analysis with blood pressure level
      as a dependent variable; no significant association between WC and blood pressure
      was obtained. Visceral fat assessment by US may be useful for epidemiological
      study and for clinics with no abdominal CT equipment for identifying high-risk
      individuals, such as those with metabolic syndrome.

PMID- 17510505
TI  - Pulse wave velocity as a marker of arteriosclerosis and its comorbidities in
      Chinese patients.
AB  - To obtain reliable data on the epidemiology of arteriosclerosis and the
      comorbidities in patients with hypertension (HP), coronary heart disease (CHD),
      type 2 diabetes mellitus (T2DM) and stroke, we evaluated the clinical
      significance of pulse wave velocity (PWV) as an indicator of arteriosclerosis and
      its comorbidities in Chinese patients. A total of 910 subjects, including 748
      Chinese patients with one or more cardiovascular risk factors (80.2% male, mean
      age 73.69+/-5.03 years) and 162 healthy volunteers (78.4% male, mean age 73.60+/
      5.32 years) were recruited into the study. PWV was measured in 910 subjects, and
      large artery arteriosclerosis was defined as PWV >or=12 m/s. Multivariable
      logistic regression analyses were performed to identify risk factors associated
      with arteriosclerosis. The prevalence of large artery arteriosclerosis in the
      patients overall was 67.4%, and the prevalence was higher in patients with than
      in those without HP (63.3% vs. 34.0%; odds ratio [OR]: 3.451), T2DM (24.8% vs.
      11.1%; OR: 2.854), CHD (56.1% vs. 45.1%; OR: 1.246) and stroke (26.6% vs. 19.2%;
      OR: 1.236), but the OR values of CHD and stroke did not differ significantly
      (p>0.05). After multiple logistic regression analysis, female sex, older age, HP
      and T2DM were risk factors for large artery arteriosclerosis. In conclusion, PWV
      can be used as a routine measurement to scan arteriosclerosis in patients with HP
      or T2DM.

PMID- 17510506
TI  - Relationship between arterial stiffness and the risk of coronary artery disease
      in subjects with and without metabolic syndrome.
AB  - We examined the influence of metabolic syndrome (MetS) on the relationship
      between arterial stiffness and the risk of coronary artery disease (CAD). In 396
      subjects (age, 63+/-11 years) who underwent coronary angiography, multiple linear
      regression analysis demonstrated that the brachial-ankle pulse wave velocity
      (PWV), but not the presence of MetS, was a significant determinant of the number
      of diseased coronary arteries (beta=0.10, p<0.05), even though both the brachial
      ankle PWV and the number of diseased coronary arteries were higher in subjects
      with MetS (n=100) than in those without MetS (n=296). However, in subjects with
      MetS, multiple linear regression analysis demonstrated that the brachial-ankle
      PWV was not a significant determinant of the number of diseased coronary
      arteries. The brachial-ankle PWV values were classified into tertile ranges in
      subjects with and without MetS. The number of diseased coronary arteries
      increased significantly with an increase in the tertile number of the brachial
      ankle PWV in the subjects without MetS (tertile 1=1.00+/-0.86, tertile 2=1.29+/
      1.01, and tertile 3=1.45+/-1.05), but not in those with MetS. In conclusion, the
      results of this study suggest that arterial stiffness is a marker of the risk of
      CAD in subjects without MetS, whereas in subjects with MetS, the syndrome may
      directly produce clinically significant atherosclerotic stenosis of the coronary
      arteries independent of its significant promotion of the development of coronary
      atherosclerosis via an increase of arterial stiffness.

PMID- 17510507
TI  - 1-Aminocyclopropanecarboxylic acid, an antagonist of N-methyl-D-aspartate
      receptors, causes hypotensive and antioxidant effects with upregulation of heme
      oxygenase-1 in stroke-prone spontaneously hypertensive rats.
AB  - 1-Aminocyclopropanecarboxylic acid (ACPC) has been shown to protect neurons
      against glutamate-induced neurotoxicity by reducing N-methyl-D-aspartate (NMDA)
      receptor activation. Recent studies have demonstrated that several antagonists of
      NMDA receptors have important cardiovascular effects. In this study, we examined
      whether the cardiovascular effects of ACPC involve the role of heme oxygenase-1
      (HO-1) and its antioxidant effect in stroke-prone spontaneously hypertensive rats
      (SHRSP). Male SHRSP were divided into two groups: a control group and an ACPC
      group administered ACPC at 50 mg/kg per day for 4 weeks by peritoneal injection.
      Systolic blood pressure (SBP) and mortality of stroke were significantly lower in
      the ACPC group than in the control group. Urinary Na(+) and Cl(-) excretion and
      plasma superoxide dismutase (SOD) activity were increased in the ACPC group.
      Western analysis detected proteins that were immunoreactive to anti-nitrotyrosine
      antibody and showed lower levels of expression in the cerebral cortex compared to
      that in the control group. Immunohistochemical analysis revealed that 8-hydroxy
      2'-deoxyguanosine (8-OHdG) formation in the hippocampus and cerebral cortex was
      reduced in the ACPC group. Quantitative reverse-transcription-polymerase chain
      reaction (RT-PCR) showed that administration of ACPC also significantly decreased
      the expression of neuronal nitric oxide synthase (nNOS) mRNA in the hippocampus
      and endotherial nitric oxide synthase (eNOS) mRNA in the cerebral cortex, and
      drastically increased HO-1 mRNA in the cerebral cortex. Enhanced HO-1 staining on
      sections from the hippocampus and cerebral cortex was observed in the ACPC group.
      These data suggest that the normalization by ACPC of blood pressure elevation and
      mortality of stroke involves induction of the expression of HO-1, which exerts
      antioxidant and vascular relaxation effects, in SHRSP.

PMID- 17510508
TI  - Postnatal blocking of interferon-gamma function prevented atherosclerotic plaque
      formation in apolipoprotein E-knockout mice.
AB  - It is unknown whether interferon-gamma has a positive or negative impact on
      atherosclerotic plaque formation. Thus, we examined the effects of postnatal
      interferon-gamma function blocking on plaque formation in apolipoprotein E
      knockout (apoEKO) mice by overexpressing a soluble mutant of interferon-gamma
      receptor (sIFNgammaR), an interferon-gamma inhibitory protein. Mice were fed a
      Western-type diet from 8 weeks of age. sIFNgammaR or mock plasmid (control) was
      injected into the thigh muscle at 8 and 10 weeks' age, because serum sIFNgammaR
      protein was transiently increased with a peak at 2 days after a single sIFNgammaR
      gene transfer and remained elevated for 2 weeks. At 12 weeks' age, control apoEKO
      mice showed marked atherosclerotic plaques from the ascending aorta to the aortic
      arch. The plaques in the aortic root had massive lipid cores and macrophage
      infiltration with thin fibrous cap and few smooth muscle cells, demonstrating low
      plaque stability. In contrast, the luminal plaque area was remarkably reduced in
      sIFNgammaR-treated apoEKO mice. sIFNgammaR treatment not only reduced lipid core
      areas and macrophage infiltration but also increased smooth muscle cell count and
      fibrotic area, suggesting improved plaque stability. In controls, interleukin
      1beta, monocyte chemoattractant protein-1, and vascular cell adhesion molecules-1
      were remarkably upregulated in the aortic wall. These changes were significantly
      reversed by sIFNgammaR. sIFNgammaR treatment had no effects on serum cholesterol
      levels. In conclusion, sIFNgammaR treatment prevented plaque formation in apoEKO
      mice by inhibiting inflammatory changes in the arterial wall. The present study
      provides insight into a new strategy for preventing atherosclerosis.

PMID- 17510509
TI  - Suppression of catechol-O-methyltransferase activity through blunting of alpha2
      adrenoceptor can explain hypertension in Dahl salt-sensitive rats.
AB  - Catecholamines have been reported to be involved in the development of salt
      sensitive hypertension. We investigated the relation between catechol-O
      methyltransferase (COMT) and salt-sensitivity. In the first experiment, Dahl salt
      sensitive (DS) rats were given a normal-salt (NS), high-salt (HS), or
      HS+hydralazine (80 mg/l water) diet for 4 or 13 weeks, and Dahl salt-resistant
      (DR) rats were given a NS or HS diet. COMT activities in both the kidneys and
      liver and urinary norepinephrine (NE) and dopamine (DA) excretion were measured.
      In the second experiment, HepG2 cells were used to investigate the role of NE in
      regulating COMT activity. In the third experiment, we investigated the reactivity
      of pre- and postsynaptic alpha(2)-adrenoceptor (AR) in DS rats. HS loading
      significantly suppressed the activities of membrane-bound COMT (MB-COMT) and,
      consistent with this finding, increased the urinary NE level in DS rats, but not
      in DR rats. Hydralazine did not restore the MB-COMT activities, which suggested
      that HS loading rather than elevated blood pressure suppressed the MB-COMT
      activities. The in vitro experiment using HepG2 cells revealed that NE increased
      the MB-COMT activity via the alpha(2)-AR. However, both the pre- and postsynaptic
      alpha(2)-AR reactivity was decreased by HS loading in DS rats. In conclusion, HS
      intake suppresses the MB-COMT activities in DS rats, presumably by blunting
      alpha(2)-AR signaling. The suppression of MB-COMT activities, consequent decrease
      in degradation of NE, and increase in NE release by blunting of alpha(2)-AR
      function may be involved in the development of salt-sensitive hypertension in DS
      rats, in whom DA-dependent natriuresis may be suppressed.

PMID- 17510511
TI  - [Radiological diagnosis of gastric cancer: double contrast method].

PMID- 17510510
TI  - Leiomyosarcoma of the abdominal aorta: a rare cause of renovascular hypertension.
AB  - We describe the case of a 44-year-old woman who presented with renovascular
      hypertension caused by primary leiomyosarcoma of the abdominal aorta that had
      metastasized into the renal arteries. Despite an extensive radiological
      evaluation, the diagnosis was mistaken first for Takayasu's arteritis and then
      for retroperitoneal hematoma or neoplasm. The patient developed renal failure due
      to bilateral renal infarction, and died 3 months after her initial presentation
      with ischemic colitis. Postmortem examination confirmed the diagnosis.

PMID- 17510513
TI  - [Framework of clinical economics].

PMID- 17510512
TI  - [Interpretation of upper gastrointestinal series: the barium-filled image].

PMID- 17510514
TI  - [The actual situation of operator radiation exposure in radioisotope
      examination].

PMID- 17510515
TI  - [The images of law: an example of duty of cofidentiality under the radiological
      technologist act].

PMID- 17510516
TI  - [Educational-industrial complex research on interactions of MR equipments with
      contact lenses].

PMID- 17510517
TI  - [The present status of regulation on radiation safety of veterinary nuclear
      medicine in Japan].

PMID- 17510518
TI  - [The international activity of JIRA International Division].

PMID- 17510519
TI  - [Examination of types of exposure and management methods for nurses in
      interventional radiology].
AB  - Although a large number of studies have been done on exposure to operators and
      doctors during interventional radiology(IVR), there have been very few reports on
      nurses. This study was carried out to clarify the situation regarding exposure
      for nurses, and provides examples of how to estimate and manage. We measured
      space dose-rate distributions with an ionization survey meter, and personal
      exposure dose by a small fluorescent grass dosimeter(Dose Ace). The experimental
      results disclosed that there tended to be two types of exposure depending on the
      task performed. Head and neck(collar level)were associated with the highest
      exposure dose, which was observed in nurses assisting operators. Alternatively,
      knees showed the highest exposure dose, which was observed in nurses observing
      and assisting the patient. When estimation of skin equivalent exposure at the
      knees is needed, it can be calculated by using the value measured at the collar
      level. Furthermore, in estimating exposure dose, the directional and energy
      characteristics of personal dosimeters should be considered adequate. For
      radiation management, a circular protective sheet can be placed around the
      patient's lower area and a protective screen near the patient's head, and basic
      and practical education can be given. We concluded that these are highly useful
      for the personal monitoring of nurses engaged in IVR.

PMID- 17510520
TI  - [Gravity sag view of lateral radiography of the knee].
AB  - The gravity sag view(GSV)is a lateral radiograph taken in the same position when
      the posterior sag sign is observed. The purpose of this study was to standardize
      the radiography technique for GSV by adjusting lateral rotation. To confirm the
      benchmark and correction angle(CA)for the GSV position, we assessed three
      dimensional(3D)CT of the GSV position of the knee using normal volunteers. The
      benchmark is established at the 3-point of the leg and adjusting the CA of the
      knee is established by estimating from Rosenberg technique radiography. This
      helped not only to correct external rotation in the initial radiography but also
      to correct rotation for repeat radiography. Our method is quantitative and highly
      reproducible, and it increases the success rate in adjusting lateral radiography
      of the knee.

PMID- 17510521
TI  - [Improved visualization of cardiac pacemaker lead on chest radiographs].
AB  - Chest radiographs provide significant information about the pacing lead for the
      management and follow-up of post-cardiac pacing patients. However, the pacing
      lead is not always clearly visible because of cardiac insertion via the
      mediastinum and low contrast on the chest radiograph. We developed an image
      processing technique that improves visualization of the cardiac pacing lead on
      chest radiographs to facilitate management after pacemaker implantation. In this
      study, 117 chest radiographs obtained during pacemaker follow-up were analyzed.
      These chest images were smoothed using a median filter, sharpened by unsharp
      masking, then binarized by thresholding using the moving average method. To
      evaluate the usefulness of these processed images, four cardiologists compared
      the original and processed images using the two-sample preference test. As a
      result, visualization of the pacing lead was significantly improved on all
      processed images compared with that on the original images. We conclude that this
      image processing technique can facilitate pacemaker management.

PMID- 17510522
TI  - [Evaluation of non-lead board as X-ray protective material].
AB  - For security, boards containing lead are commonly used to partition off rooms
      adjacent to radiation facilities. From the viewpoints of environmental safety and
      of material recycling during the process of remodeling or repair, however, the
      trend is toward avoiding the use of lead-containing radiation-protection board.
      Consequently, we developed a lead-free board(W 910xH 1820xD 12.5 mm)composed of a
      mixed material incorporating calcium sulfate and barium sulfate to be used as a
      partition at a diagnostic X-ray institution. The mass attenuation coefficients of
      the lead-free board were lower by about 12% and 60% for energy ranges of 25
      approximately 37 keV and 38 approximately 41 keV, respectively, as compared with
      those of lead. Lead equivalents for the newly developed board(12.5 mm
      thickness)were 0.87+/-0.01 mmPb at 100 kV tube voltage, 0.60+/-0.01 at 125 kV,
      and 0.47+/-0.01 at 150 kV. A double-layer lead-free board proved to have enough
      shielding ability even at usual photographic frequencies.

PMID- 17510523
TI  - [Assessment of physical frame-based abdominal thickness estimation by evaluating
      conditions with fuzzy control: automatic exposure control (AEC) in diagnostic X
      ray apparatus].
AB  - In digital X-ray photography of the abdomen and lumbar vertebrae, the automatic
      exposure control(AEC)system installed in the radiographic stand is essential for
      imaging at an appropriate dose. The AEC system has been used in many medical
      facilities. As patient size needs to be adapted, currently available AEC systems
      are equipped with a mechanism that enables an increase/decrease, by stages of 7
      9, in AEC for X-ray dose. Adjustment of this function, however, depends largely
      on the radiologist's experience, as such X-ray dose control is lacking in
      reproducibility and quantification. We performed fuzzy reasoning using a measure
      of obesity(body-mass index: BMI)that was determined from the patient's height and
      body weight and estimated his/her abdominal thickness. On the basis of this
      estimated value, we established a methodology to define the conditions for X-ray
      photography of abdominal thickness in the area of increased patient thickness. We
      speculated that this methodology might provide better reproducibility and
      quantification for X-ray dose control in the area of increased patient thickness
      than the conventional AEC system.

PMID- 17510524
TI  - 2-hydroxycinnamaldehyde inhibits SW620 colon cancer cell growth through AP-1
      inactivation.
AB  - Cinnamaldehyde derivatives isolated from Cinnamomum cassia have been widely used
      for treating dyspepsia, gastritis, and inflammatory disease as well as cancer. To
      investigate the anti-tumor activities of several cinnamaldehyde derivatives, we
      compared the inhibitory effect of cinnamaldehyde derivatives on cell growth and
      AP-1 transcriptional activity in SW620 human colon cancer cells since AP-1 is a
      transcriptional factor implicated to control cancer cell growth. Among the
      derivatives, 2'-hydroxycinnamaldehyde (HCA) most significantly inhibited cancer
      cell growth and AP-1 transcriptional activity in a dose-dependent manner with an
      IC50 value of 12.5 and 9 microg/ml, respectively. In further studies on the
      mechanism, we found that consistent with the inhibitory effect on cell growth,
      HCA dose-dependently (0-20 microg/ml) inhibited DNA binding activity of AP-1
      accompanied with down regulation of c-Jun and c-Fos expressions. HCA also induced
      apoptotic cell death as well as expression of the apoptosis-regulating gene
      caspase-3, but inhibited the anti-apoptosis regulating gene bcl-2 in a dose
      dependent manner. These results suggested that HCA has the most potent inhibitory
      effect against human colon cancer cell growth, and AP-1 may be an important
      target of HCA.

PMID- 17510525
TI  - Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced
      apoptosis in hippocampus-derived adult neural stem cells.
AB  - Desipramine (DP) is a tricyclic antidepressant used for treating depression and
      numerous other psychiatric disorders. Recent studies have shown that DP can
      promote neurogenesis and improve the survival rate of hippocampal neurons.
      However, whether DP induces neuroprotection or promotes the differentiation of
      neural stem cells (NSCs) needs to be elucidated. In this study, we cultured NSCs
      derived from the hippocampal tissues of adult rats as an in vitro model to
      evaluate the modulation effect of DP on NSCs. First, we demonstrated that the
      expression of Bcl-2 mRNA and nestin in 2 microM DP-treated NSCs were up-regulated
      and detected by real-time reverse transcriptase polymerase chain reaction (RT
      PCR). The results of Western blotting and immunofluorescent study confirmed that
      Bcl-2 protein expression was significantly increased in Day 3 DP-treated NSCs.
      Using the Bcl-2 small interfering RNA (siRNA) method, our results further showed
      that DP protects the lipopolysaccharide (LPS)-induced apoptosis in NSCs, in part
      by activating the expression of Bcl-2. Furthermore, DP treatment significantly
      inhibited the induction of proinflammatory factor interleukin (IL)-1beta, IL-6,
      and tumor necrosis factor-alpha in the culture medium of LPS-treated NSCs
      mediated by Bcl-2 modulation. The results of high performance liquid
      chromatography coupled to electrochemical detection further confirmed that DP
      significantly increased the functional production of serotonin (26+/-3.5 microM,
      DP-treated 96 h) and noradrenaline (50+/-8.9 microM, DP-treated 96 h) in NSCs
      through activation of the MAPK/ERK pathway and partially mediated by Bcl-2. In
      conclusion, the present results indicate that DP can increase neuroprotection
      ability by inhibiting the LPS-induced inflammatory process in NSCs via the
      modulation of Bcl-2 expression, as confirmed by the siRNA method.

PMID- 17510526
TI  - Nitric oxide-donating genistein prodrug: design, synthesis, and bioactivity on
      MC3T3-E1 cells.
AB  - To find a more potent alternative with less estrogen-related side effects for
      hormone replacement therapy, we designed and synthesized a nitric oxide (NO)
      releasing prodrug of genistein, named NO-donating genistein (NO-G). The
      characteristics of NO-G were determined by melting point, NMR spectroscopy, and
      mass spectrometric analysis. HPLC has been used to test the new prodrug's
      stability. The releasing capacity of NO-G was tested by Griess reagent in vitro.
      The bioactivities of NO-G on proliferation, differentiation, and mineralization
      of the osteoblastic cell line MC3T3-E1 were determined by MTT assay, flow
      cytometric analysis, measurement of the alkaline phosphatase (ALP) activity and
      the secreted osteocalcin (OCN), and Alizarin Red-S staining. The product showed
      1H NMR spectra and relative molecular mass in agreement with the designed
      structure, and it was stable in buffer solution. NO-G continually released low
      level NO within 5 h in MC3T3-E1 cells. NO-G caused a significant elevation of
      cell growth, ALP activity, and OCN secretion in both dose- and time-dependent
      manner. Furthermore, the Alizarin Red-S staining showed that NO-G promoted
      mineralization of MC3T3-E1 cells. These effects were all significantly greater
      than those of its parent drugs. The results suggested that NO-G might be a novel
      drug for the treatment of postmenopausal osteoporosis.

PMID- 17510527
TI  - In vitro development of equine oocytes from preserved ovaries after
      intracytoplasmic sperm injection.
AB  - In this study, we evaluated the meiotic competence of equine oocytes from ovaries
      preserved for one day. We also investigated fertilization, cleavage rate,
      developmental competence and freezability of equine embryos after
      intracytoplasmic sperm injection (ICSI). After collection from ovaries, the
      oocytes were classified into two groups comprised of those having compact cumulus
      layers (Cp) or those having expanded cumulus layers (Ex). Oocytes with a first
      polar body were subjected to fertilization by ICSI using frozen-thawed stallion
      spermatozoa and were then cultured in CR1aa medium. The rates of metaphase II
      stage oocytes, normal fertilization and cleavage were not significantly different
      between the two oocyte categories (38.5, 70.0 and 48.7% for CP and 43.5, 60.0 and
      58.8% for Ex, respectively). However, the blastocyst development rate of Ex was
      significantly (P<0.05) higher than that of Cp (25.5 vs. 7.7%). Three Cp-derived
      and 12 Ex-derived early blastocysts were cryopreserved using the slow cooling
      protocol, and all of them developed to hatching blastocysts after thawing. These
      results suggest that equine oocytes fertilized by ICSI can develop to the
      preimplantation stage in culture conditions similar to those used in the bovine.
      Furthermore, the Ex oocytes had higher developmental competence than the Cp
      oocytes, and the in vitro-produced blastocysts had high viability after freezing
      and thawing.

PMID- 17510528
TI  - Induction of ovulation with GnRH and PGF(2 alpha) at two different stages during
      the early postpartum period in dairy cows: ovarian response and changes in
      hormone concentrations.
AB  - The aims of this study were 1) to determine whether dairy cows can be induced to
      ovulate by the treatment with gonadotropin releasing hormone (GnRH) followed by
      prostaglandin F(2 alpha) (PGF(2 alpha)) during the early postpartum period and 2)
      to describe their ovarian and hormonal responses according to ovarian status.
      Cows were divided in two groups and received 10 microg of buserelin followed by
      500 microg of cloprostenol 7 days apart starting from 21 (GnRH21, n=7) or around
      37 days postpartum (GnRH37, n=7). The groups were further classified according to
      presence (-CL) or absence (-NCL) of functional corpora lutea (CL) on the day of
      GnRH treatment (d 0): GnRH21-NCL (n=4), GnRH21-CL (n=3) and GnRH37-CL (n=7).
      Ovarian morphology was monitored and the concentrations of P(4), E(2), FSH and
      insulin-like growth factor 1 (IGF-1) were measured. All cows ovulated after
      administration of GnRH. The P(4) levels of the GnRH21-NCL group from d 0 to d 5
      were lower than those of the GnRH21-CL (P<0.05) and GnRH37-CL groups (P<0.01). In
      contrast, the E(2) levels of the GnRH21-NCL group within d 2 to d 6 were higher
      (P<0.05) than those of the other groups. Compared with the GnRH37-CL group, the
      GnRH21-NCL group had more small follicles on d 2 (P<0.05), d 3 (P<0.01) and d 4
      (P<0.01) and more large follicles on d 5 (P<0.05). The induced CL and new
      ovulatory follicles were larger in the GnRH21-NCL group compared with the GnRH21
      CL (P<0.001 and P<0.01) and GnRH37-CL groups (P<0.001 and P<0.05). IGF-1 did not
      differ among the groups. The GnRH21-NCL group had higher FSH levels than the
      GnRH21-CL (P<0.01) and GnRH37-CL groups (P<0.001) on d 0. Low P(4) and high FSH
      levels may suggest higher gonadotropin support on the enhanced ovarian morphology
      of the GnRH21-NCL group. PGF(2 alpha) treatment induced CL regression and
      subsequent ovulation in 3/4 (75%), 3/3 (100%) and 7/7 (100%) cows in the GnRH21
      NCL, GnRH21-CL and GnRH37-CL groups, respectively. In conclusion, a 7-day GnRH
      PGF(2 alpha) synchronization protocol can effectively induce dairy cows to
      ovulate as early as 21 days postpartum, regardless of ovarian status.

PMID- 17510529
TI  - Attempt at intracytoplasmic sperm injection of in vitro matured oocytes in common
      minke whales (Balaenoptera acutorostrata) captured during the Kushiro Coast
      Survey.
AB  - The present study was conducted during the Kushiro Coast Survey in an attempt to
      produce common minke whale embryos. In Experiment 1, we attempted to determine
      the appropriate culture duration (30 or 40 h) for in vitro maturation (IVM) of
      immature oocytes using the Well of the Well method. In Experiment 2, and
      intracytoplasmic sperm injection (ICSI) was applied to matured oocytes from
      prepubertal and adult common minke whales after IVM culture (40 or 48 h), and
      then their embryonic development was assessed. In Experiment 1, the maturation
      rate of oocytes cultured for 40 h (30.4%) was significantly higher than that of
      oocytes cultured for 30 h (6.8%; P<0.01). In Experiment 2, a total of 35 and 46
      immature oocytes derived from adult (n=2) and prepubertal (n=6) minke whales,
      respectively, were cultured for 40 or 48 h. The maturation rate in the oocytes
      from the adult whales (34.2%) tended to be higher than that of the oocytes from
      the prepubertal whales (19.6%), but there was no significant difference.
      Following ICSI, 3 out of the 10 inseminated and cultured oocytes from the adult
      whales cleaved (2-, 8-, and 16-cell stages); all of these oocytes had been
      matured for 40 in culture. However, these oocytes did not develop to further
      stages. Only one of the 6 oocytes derived from the prepubertal whales, IVM
      cultured for 40 h and inseminated, developed to the 4-cell stage. The present
      results indicate that a 40 h IVM culture produces significantly higher rates of
      in vitro maturation than a 30 h IVM culture for common minke whale oocytes.
      Following ICSI, some oocytes cleaved to the 16-cell stage, but no further
      development was observed.

PMID- 17510530
TI  - The relationship between oocyte morphology and ovarian status in cattle.
AB  - We investigated the relationships between oocyte morphology, follicular size and
      follicular waves using bovine ovaries derived from local abattoirs. Ovaries at
      the recruitment and selection phases contained larger numbers of oocytes with
      good developmental ability, although ovaries at the recruitment phase contained
      the largest numbers of follicles compared with ovaries at the selection and
      dominant phases. Dominant phase ovaries contained a high percentage of oocytes
      with as good developmental ability as selection phase ovaries; however, they
      contained the lowest total number of oocytes with good developmental ability.
      Small follicles under 3.0 mm in diameter contained large numbers of small and
      degenerating oocytes. In contrast, follicles more than 3.0 mm in diameter
      contained a higher percentage of oocytes with good developmental ability.

PMID- 17510531
TI  - Characterization of NKT-cell hybridomas expressing invariant T-cell antigen
      receptors.
AB  - Two natural killer T (NKT)-cell hybridomas were established by fusing sorted NKT
      cells with BW1100 thymoma cells. The first hybridoma line, 1B6, was CD4(+)8(-),
      whereas the second one, 2E10, was CD4(low)8(-). Initial characterizations
      revealed that both cell lines expressed an invariant T cell antigen receptor,
      which could be readily detected with alpha-galactosylceramide-loaded CD1d : Ig
      fusion protein (alpha-GalCer/CD1d). Sequence analyses of the alpha and beta
      chains of the T cell receptor V genes revealed that 1B6 and 2E10 cells expressed
      V alpha 14J alpha 18/V beta 8.2D beta 2J beta 2.7 and V alpha 14J alpha 18/V beta
      8.1D beta 1J beta 1.1, respectively. When these hybridoma cells were stimulated
      with immobilized anti-CD3 monoclonal antibodies, alpha-GalCer/CD1d, or alpha
      GalCer in the presence of antigen-presenting cells, they produced IL-4 and IFN
      gamma. The expression levels of CD69, CD154, and CD178 were concomitantly up
      regulated on both hybridomas upon stimulation. Because it is difficult to isolate
      a sufficient number of NKT cells, these hybridomas should provide useful
      platforms to study a variety of functions of NKT cells.

PMID- 17510532
TI  - Demonstration of chimeric DNA of bcl-2 and immunoglobulin heavy chain in
      follicular lymphoma and subsequent Hodgkin lymphoma from the same patient.
AB  - We performed single cell polymerase chain reaction (PCR) amplification of the t
      (14 ; 18) translocation from paraffin embedded sections in a case of follicular
      lymphoma (FL) with subsequent development of Hodgkin lymphoma (HL). The lymphoma
      cells of FL were positive for CD20, CD10 and BCL-2, and negative for CD3, CD30
      and CD15. Hodgkin and Reed-Sternberg (HRS) cells of HL were positive for CD20,
      CD30 and CD15, and negative for CD3 and CD10. EBER-1 RNA in situ hybridization
      failed to stain with both lymphomas. HRS cells manipulated and FL cells micro
      shaved from individual neoplastic follicles were subjected to single-cell PCR.
      The t (14 ; 18) translocation, a chimeric DNA containing portions of the bcl-2
      and the immunoglobulin heavy chain (IgH) genes, was amplified from four of 27
      isolated HRS cells and two individual FL follicles. All t (14 ; 18) PCRs yielded
      products of the same size, and an identical nucleotide sequence including the t
      (14 ; 18) translocation was found in both FL and HRS samples. Thus, the data
      demonstrate the common clonal origin of FL cells and HRS cells in subsequent HL,
      and that both FL and HL were derived from germinal center B cells with the t (14
      ; 18) translocation.

PMID- 17510533
TI  - Frequent DNA methylation but not mutation of the ID4 gene in malignant lymphoma.
AB  - ID4 is a member of the inhibitor of DNA binding (ID) family, and inhibits the
      binding of basic helix-loop-helix transcription factors to DNA. In some malignant
      tumors, ID4 is inactivated by promoter hypermethylation, and is thought to be a
      candidate tumor suppressor gene (TSG). We have found that the promoter region of
      the ID4 gene is frequently methylated in lymphoid cell lines (100%, 9/9), primary
      diffuse large B-cell lymphoma (95%, 19/20), and follicular lymphoma (100%,
      10/10). Somatic mutation of the ID4 gene was also examined, and no mutations were
      found. These findings suggest that the ID4 gene might be inactivated by DNA
      hypermethylation, and may function as a TSG in malignant lymphoma.

PMID- 17510534
TI  - Secondary sea-blue histiocytosis derived from Niemann-Pick disease.
AB  - Sea-blue histiocytosis is a rare disorder seen in patients with lipid metabolic
      or ceroid storage diseases. Sea-blue histiocytes are ceroid-laden macrophages
      detectable by May-Giemsa staining. We report a case of a 28-year-old woman
      diagnosed with Niemann-Pick disease at 2 or 3 years of age. To confirm this
      diagnosis, we examined her bone marrow, which revealed scattered foci containing
      aggregates of foamy macrophages. May-Giemsa staining identified blue-staining
      foamy macrophages, referred to as sea-blue histiocytes. In summary, we report the
      detection of sea-blue histiocytosis in an adult with Niemann-Pick disease.

PMID- 17510535
TI  - Spontaneous regression of diffuse large B-cell lymphoma harbouring Epstein-Barr
      virus: a case report and review of the literature.
AB  - We report an elderly patient with diffuse large B cell lymphoma harbouring
      Epstein-Barr virus that showed spontaneous regressions with subsequent relapses
      three times. The patient died of aspiration pneumonia without any anti-neoplastic
      treatment 5 years 10 months after the initial onset of lymph node swelling. In
      the literature, there are several reports of aggressive non-Hodgkin's lymphoma
      cases that showed spontaneous regressions without relapse till the last
      observation. Over half of the cases were the extra-nodal type. The tendency
      toward regression of swollen lymph nodes detected by clinicians occurs within 2
      weeks after biopsy. If the remaining lymph nodes show a tendency to decrease in
      size after biopsy without any anti-tumor therapies, the patient may develop
      spontaneous regression.

PMID- 17510536
TI  - Neurography of the spinal nerve roots by diffusion tensor scanning applying
      motion-probing gradients in six directions.
AB  - PURPOSE: Diffusion-weighted (DW) magnetic resonance (MR) imaging of the nerve
      roots and peripheral nerves has been reported. We applied a sequence similar to
      brain diffusion tensor (DT) tractography to such a technique and assessed its
      feasibility. METHODS: On a 1.5-T MR system, we acquired DW images in the axial
      plane using a single-shot echo-planar short tau inversion-recovery (STIR)-based
      sequence. Motion-probing gradients (MPGs) were applied in 6 directions with a b
      value of 500 s/mm(2). For postprocessing, we performed maximum-intensity
      projection to reconstruct the images. We obtained cervical spine images from 3
      volunteers and 8 patients and thoracolumbar spine images from 3 volunteers and 6
      patients. On the source images of the cervical spine obtained from the
      volunteers, we compared the signal-to-noise ratios (SNRs) of the neural
      structures between images obtained applying MPG in 6 directions and in 3
      directions. We visually assessed the nerve roots and proximal portions of the
      contiguous peripheral nerves in the images from volunteers and patients. RESULTS:
      The SNRs were significantly superior in the images obtained with the application
      of MPGs in 6 directions to those obtained with the application of MPGs in 3
      directions (P<0.01). Visual assessment demonstrated the nerve roots as well as
      the nerve ganglia and the contiguous peripheral nerves up to 3 cm or more from
      the respective neural foramina in each subject. Image distortion was minimal.
      CONCLUSIONS: Our technique provides neurographic images of the nerve roots and
      proximal portions of the contiguous peripheral nerves, and images obtained using
      our sequence applying MPGs in 6 directions are superior to those obtained in 3
      directions.

PMID- 17510537
TI  - Magnetic resonance findings of primary uterine malignant lymphoma.
AB  - To clarify the magnetic resonance (MR) characteristics of primary uterine
      malignant lymphoma, we identified 4 patients with primary uterine lymphoma in the
      MR database of our institute from 1994 to 2005 and evaluated their clinical and
      MR findings for tumor extension, size, shape, and signal intensity, multinodular
      growth pattern, preservation of normal endometrium, and lymphadenopathy. In all 4
      patients, tumors extended to the uterus and vagina or parametrium, and uterine
      tumors showed relatively homogeneous intensity on both T(1)- and T(2)-weighted MR
      imaging. Two patients showed multinodular tumor growth; three revealed pelvic
      lymphadenopathy; and none had intact endometrium or normal uterine zonal
      structure. Thus, large tumors with relatively homogeneous signal intensity seemed
      to be a specific MR finding of uterine lymphoma, and findings of multinodular
      growth were considered a possible characteristic suggesting the uterine
      involvement of malignant lymphoma.

PMID- 17510538
TI  - Image quality using dynamic MR imaging of the temporomandibular joint with true
      FISP sequence.
AB  - We evaluated the quality of dynamic magnetic resonance (MR) imaging of the
      temporomandibular joint (TMJ) in 20 normal volunteers with 40 TMJs. To confirm
      TMJ, we obtained static proton density weighted images (PDWI) before performing
      dynamic MR imaging with true-fast imaging in a steady-state precession (true
      FISP) sequence. Four sequences of the first 10 volunteers were examined to
      determine the optimal sequence. The 4 sequences included the integrated parallel
      acquisition technique (iPAT) and/or fat saturation technique. The optimal
      sequence was then determined and performed in all 20 volunteers. The quality of
      imaging was evaluated, especially with respect to the conspicuity of the
      articular disk, mandibular condyle, articular eminence and lateral pterygoid
      muscle. One of 3 confidence levels was assigned for this evaluation. Neither iPAT
      nor fat saturation obtained the best quality imaging. Detection rates in the 20
      volunteers were 83% for the articular disk, 95% for the mandibular condyle, 96%
      for the articular eminence and 7.5% for the lateral pterygoid muscle. We
      recommend dynamic MR imaging of the TMJ with the true-FISP sequence using neither
      iPAT nor fat saturation. Nevertheless, dynamic MR imaging was inferior to static
      imaging in detecting the articular disk and still requires improvement.

PMID- 17510539
TI  - Detecting breast cancer with non-contrast MR imaging: combining diffusion
      weighted and STIR imaging.
AB  - We combined diffusion-weighted (DWI) and short TI inversion recovery (STIR)
      imaging to evaluate the diagnostic capability of non-contrast magnetic resonance
      (MR) imaging to detect breast cancer. Seventy women patients underwent
      mammography and MR imaging with combined DWI (b factor: 1000) and STIR that
      revealed malignancy, and postoperative pathological examination confirmed breast
      cancer. Interpreted images were evaluated for sensitivity, false negative rate
      (FN), sensitivity by pT, and sensitivity by background density of the mammary
      gland. Of the 70 cases, 68 were diagnosed as cancer by DWI and STIR (sensitivity,
      97% [68/70]; FN, 2.9% [2/70]). Sensitivities by pT were: pTis, 67% (4/6); pT1,
      100% (33/33); and pT2-4, 100% (31/31). No significant differences were observed
      in sensitivity between pT1 and pT2-4 (P<0.001). Sensitivities by background
      density of mammary gland were: fatty/scattered fibroglandular tissue, 95% (20/21)
      and heterogeneous fibroglandular tissue/mostly fibroglandular tissue, 98%
      (48/49). No significant differences were observed (P<0.001). Two cases, an
      intraductal and an apocrine carcinoma, were incorrectly diagnosed by MR imaging.
      Precise diagnosis of breast cancer is possible with combined DWI and STIR, even
      in non-contrast MR imaging, regardless of the diameter or background density of
      mammary gland. It is hoped that non-contrast MR imaging that combines DWI and
      STIR will become an established clinical screening method.

PMID- 17510540
TI  - New horizons in MR technology: RF coil designs and trends.
AB  - Parallel imaging techniques have developed very rapidly, and realization of their
      full potential has required the design of magnetic resonance (MR) scanners with
      ever-increasing numbers of receiver channels (32 to 128). In particular, 1.5- and
      3-Tesla fast MR imaging applications are now used in everyday clinical practice.
      Both strengths require maximum achievable signal-to-noise ratio (SNR) and multi
      detector array coil optimization within the framework of the parallel imaging
      scheme for more advanced and faster clinical MR scanning. Preamplifiers are key
      components in the detector array coils and serve many functions beyond mere
      signal amplification. One critical function is to aid in the decoupling of
      individual coils, which is essential for optimal SNR and the performance of
      parallel imaging. To support a large number of detector array coils for parallel
      imaging, preamplifiers must be physically very small so that they may be tightly
      packed together to form an optimized detector array. The author herein reviews
      the state-of-the-art work reported by those skilled in the art to consider the
      rationale for determining how many channels are enough and how fast we can go.
      The paper explores the important and fundamental principles of RF array coils for
      MR imaging and reviews cutting-edge array coils, including those for transmit
      SENSE or parallel transmission applications. The future of radiofrequency (RF)
      coil technology is also considered.

PMID- 17510541
TI  - MR imaging in patients with suspected liver metastases: value of liver-specific
      contrast agent Gd-EOB-DTPA.
AB  - The appropriate staging of malignant tumors is increasingly important as new
      therapeutic strategies develop. Because metastatic involvement of the liver in
      extrahepatic malignant disease may significantly change therapeutic approach, it
      is important to rule out such involvement with high confidence. Moreover, the
      differentiation between incidental benign lesions, such as hemangioma, focal
      nodular hyperplasia (FNH), or adenoma, is of high interest. Magnetic resonance
      (MR) imaging has proved reliable for diagnostic work-up of the liver. Liver
      specific contrast agents have been especially helpful in detecting and precisely
      characterizing focal liver lesions, but the use of these agents has been limited
      because it has not been possible to perform both proper vascular phase and liver
      specific phase within a reasonable time frame and in a single examination after a
      single injection of contrast agent. However, the hepatobiliary contrast agent
      gadolinium-ethoxybenzyl (Gd-EOB)-DTPA now allows combined dynamic imaging and
      hepatocyte-specific imaging in one examination. Gd-EOB-DTPA can be injected as a
      bolus and shows the enhancement characteristics and vascularity of liver lesions.
      In the delayed phase, which is acquired most appropriately 20 min after
      injection, Gd-EOB-DTPA is taken up selectively by functioning hepatocytes. Thus,
      malignant liver lesions, e.g. metastases, are spared from contrast uptake of the
      surrounding liver parenchyma. These lesions are hypointense in contrast to the
      surrounding bright liver. We review the current literature and present a
      practical approach to Gd-EOB-enhanced MR imaging using imaging examples of
      patients with liver metastases.

PMID- 17510542
TI  - A case of Gerstmann-Straussler-Scheinker syndrome.
AB  - Gerstmann-Straussler-Scheinker syndrome (GSS syndrome) is a rare hereditary
      disorder caused by prion protein gene mutation. We present the case of a 31-year
      old man, whose signs and symptoms gradually progressed from loss of attention
      while driving at onset to headache, dysarthria, night sweat, fatigue, and
      dysgraphia. Diffusion-weighted imaging (DWI) of the brain after admission showed
      high signal intensities in the bilateral caudate nuclei, bilateral thalami, and
      cerebral cortices that suggested transmissible spongiform encephalopathy. The
      patient was diagnosed with GSS syndrome on genetic study. Magnetic resonance (MR)
      imaging of the entire period of sickbed showed gradually changing signal
      intensities and cerebral atrophy. We present a series of images and discuss the
      reasons for the abnormal intensities in GSS syndrome that vary among reported
      cases.

PMID- 17510543
TI  - The "morning glory sign" should be evaluated using thinly sliced axial images.

PMID- 17510544
TI  - Stress distribution in maxillary alveolar ridge according to finite element
      analysis using micro-CT.
AB  - The purpose of the present study was to evaluate stress distribution by finite
      element analysis in an accurate model simulating trabecular bone using micro-CT.
      Dentulous and edentulous maxillary jaws of Japanese adult cadavers were used (5
      sides each; total, 10 sides). Imaging was performed using a micro-CT, followed by
      reconstruction with 3-D images. Finite element analysis models were developed
      using the maxilla with average bone morphometry. A load corresponding to occlusal
      force was applied in different loading conditions, followed by evaluation of
      stress distribution. In dentulous maxillas, a load was applied in the dental axis
      direction to the first molar crown (LD). In edentulous maxillas, a load was
      applied directly to a circular area 4mm in diameter (LER0) to a cylinder 4mm in
      diameter and 10mm in height (LER10) corresponding to the first molar area. Stress
      was concentrated in cortical bone around the first molar, trabecular bone and
      cortical bone at the maxillary sinus base in LD, cortical bone of the alveolar
      ridge in LER0, and trabecular bone around the cylinder and cortical bone at the
      maxillary sinus base in LER10. LER0 showed a stress distribution markedly
      different from that in LD. Compared with LER0, LER10 showed a stress distribution
      close to that in LD. A model simulating trabecular bone allows a more accurate
      evaluation of stress distribution.

PMID- 17510545
TI  - Longitudinal study of prolonged breast- or bottle-feeding on dental caries in
      Japanese children.
AB  - The aim of this investigation was to study the effects of prolonged breast- or
      bottle-feeding on dental caries in Japanese infants. This longitudinal study was
      conducted by means of a questionnaire and clinical examination of 592 children at
      18 months, 2 years and 3 years of age. The children were divided into three
      groups: 1) children still being breast-fed at 18 months of age (n=42); 2)
      children still being bottle-fed at 18 months of age (n=45); and 3) children
      weaned off of breast- or bottle-feeding and with no nonnutritive-sucking habits
      at 18 months of age (n=205). Results showed that breast-feeding at 18 months of
      age produced many significant differences to the control children, including a
      higher prevalence of caries and higher number of dft. However, no significant
      differences were observed between bottle-fed and control children. In conclusion,
      our results suggest that prolonged breast-feeding at an early age before primary
      dentition has fully erupted is a risk factor for dental caries. Therefore, breast
      fed children need to be monitored more closely, and aggressive methods of
      preventive care need to be instituted. It is also important to identify factors
      related to dental caries among breastfed children as soon as possible, and
      develop effective preventive programs.

PMID- 17510546
TI  - Characteristics of breast-fed children with nursing caries.
AB  - The aim of this study was to investigate the characteristics and risk factors of
      prolonged breast-feeding in children. A total of 105 children aged 18 months were
      screened for ongoing breast-feeding at a public health center. Of these, 105
      children were selected for a more comprehensive examination, involving
      investigation of dietary, tooth-brushing habits and oral hygiene. The children
      were examined again, and initial and manifest caries were recorded at 24 months
      of age. As a result, 20 (19.0%) of the 105 children had caries at 24 months of
      age. Logistic regression analysis revealed an association between caries and
      bedtime breast-feeding (p=0.003). Oral hygiene at 18 months of age was also
      correlated with caries (p=0.015). It was concluded that reducing the frequency of
      feeding, early establishment of good oral hygiene habits and also regular visits
      to the dentist are essential in preventing nursing caries in prolonged breast-fed
      children.

PMID- 17510547
TI  - Age-related differences in localization of beta-defensin-2 in human gingival
      epithelia.
AB  - Defensins are known to play an important role in defense against bacteria. It is
      also known that immunity against infection is compromised with age. The purpose
      of this study was to evaluate the localization of human beta-defensin (HBD)-2 in
      human gingival epithelia according to age. Gingival epithelia in maxillary
      premolar buccal normal regions was immunohistochemically stained for HBD-2.
      Specimens were divided into two groups: 6 cases in a young group (<20 years old)
      and 7 cases in an elderly group (>50 years old). Expression of HBD-2 in gingival
      epithelium in young subjects was mostly detected in the superficial layer of the
      parakeratinized layer, while some areas of the spinous cell layer in elderly
      subjects were positive for HBD-2, as was the superficial layer. Two cases in the
      young group and 5 cases in the elderly group immunoreacted with HBD-2 in the
      spinous cell layer. Furthermore, immunoreaction was stronger in the elderly
      group. The results revealed HBD-2 positive cells in spinous cells in the elderly
      group and in the parakeratinized layer in the young group.

PMID- 17510548
TI  - Cyto- and chemoarchitecture of the cerebellum of the short-beaked echidna
      (Tachyglossus aculeatus).
AB  - The monotremes (echidnas and platypus) have been claimed by some authors to show
      'avian' or 'reptilian' features in the gross morphology and microscopic anatomy
      of the cerebellum. We have used Nissl staining in conjunction with enzyme
      histochemistry to acetylcholinesterase and cytochrome oxidase and
      immunohistochemistry to non-phosphorylated neurofilament protein (SMI-32
      antibody), calcium binding proteins (parvalbumin, calbindin and calretinin) and
      tyrosine hydroxylase to examine the cyto- and chemoarchitecture of the cerebellar
      cortex and deep cerebellar nuclei in the short-beaked echidna. Immunoreactivity
      for non-phosphorylated neurofilament (SMI-32 antibody) was found in the deep
      cerebellar nuclei and in Purkinje cells of most regions except the nodule.
      Purkinje cells identified with SMI-32 immunoreactivity were clearly mammalian in
      morphology. Parvalbumin and calbindin immunoreactivity was found in Purkinje
      cells with some regional variation in staining intensity and in Purkinje cell
      axons traversing cerebellar white matter or terminating on Lugaro cells.
      Calbindin immunoreactivity was also present in inferior olivary complex neurons.
      Calretinin immunoreactivity was found in pontocerebellar fibers and small cells
      in the deep granule cell layer of the ansiform lobule. We found that, although
      the deep cerebellar nuclei were much less clearly demarcated than in the rodent
      cerebellum, it was possible to distinguish medial, interposed and lateral nuclear
      components in the echidna. As far as we can determine from our techniques, the
      cerebellum of the echidna shows all the gross and cytological features familiar
      from the cerebellum of therian mammals.

PMID- 17510549
TI  - Overall brain size, and not encephalization quotient, best predicts cognitive
      ability across non-human primates.
AB  - For over a century, various neuroanatomical measures have been employed as assays
      of cognitive ability in comparative studies. Nevertheless, it is still unclear
      whether these measures actually correspond to cognitive ability. A recent meta
      analysis of cognitive performance of a broad set of primate species has made it
      possible to provide a quantitative estimate of general cognitive ability across
      primates. We find that this estimate is not strongly correlated with
      neuroanatomical measures that statistically control for a possible effect of body
      size, such as encephalization quotient or brain size residuals. Instead, absolute
      brain size measures were the best predictors of primate cognitive ability.
      Moreover, there was no indication that neocortex-based measures were superior to
      measures based on the whole brain. The results of previous comparative studies on
      the evolution of intelligence must be reviewed with this conclusion in mind.

PMID- 17510550
TI  - Acute pancreatitis in the Guangdong Province, China.
AB  - BACKGROUND/AIMS: Many studies have recently been published on acute pancreatitis;
      however, few large-sample studies have been focused on the risk factors for
      deaths in severe acute pancreatitis. To address this issue, the present study was
      intended to assess etiology, severity, and mortality of acute pancreatitis in the
      Guangdong Province (Guangdong), China, and to analyze the risk factors
      responsible for deaths in severe acute pancreatitis in this large series of
      patients. METHODS: Four tertiary medical centers located in Guangdong were
      involved in this retrospective study. Data of 2,342 patients with acute
      pancreatitis admitted to these centers from December 1990 through December 2005
      were collected in a standardized form and analyzed. RESULTS: Of the 2,342
      patients (1,130 men and 1,212 women, mean age 51+/-18, range 4-98 years), 1,778
      (76.0%) had mild pancreatitis, and 564 (24.0%) had the severe form. Biliary tract
      disease (47.5%) was the predominant etiology, the overall mortality rate was
      5.0%, and the fatality rate in patients with severe acute pancreatitis was 20.0%.
      Among the deceased patients in the severe acute pancreatitis group, logistic
      regression analysis of variables showed that the independent risk factor for
      mortality was shock, while a biliary origin was a protective factor against a
      poor prognosis. CONCLUSIONS: In this case series, the results suggest that
      biliary tract disease was the main etiologic factor of acute pancreatitis in
      Guangdong. The majority of deaths in severe acute pancreatitis occurred within
      the first 14 days of admission; the only independent risk factor for mortality
      was systematic complication of shock.

PMID- 17510551
TI  - Gastric electrical stimulation for the treatment of gastroparesis: ready for
      prime time?

PMID- 17510552
TI  - Tegaserod inhibits the serotonin transporter SERT.
AB  - BACKGROUND: Tegaserod is a novel drug for the treatment of constipation
      predominant irritable bowel syndrome. Tegaserod is thought to exert its
      prokinetic effect as a selective partial agonist of serotonin receptor type 4 (5
      HT4) receptors located in the enteric nervous system. It is unknown, however,
      whether tegaserod interacts with the human serotonin reuptake transporter (hSERT)
      and the uptake transporters for dopamine (hDAT) and norepinephrine (hNET).
      Therefore, the aim of the present study was to investigate whether tegaserod
      inhibits SERT-, DAT-, and NET-mediated transport. METHODS: Tegaserod inhibition
      of SERT-mediated [3H]5-HT and NET- and DAT-mediated [3H]dopamine uptake was
      measured in human embryonic kidney (HEK) 293 cells stably expressing hSERT, hDAT,
      and hNET in comparison with untransfected control HEK293-FT cells. RESULTS:
      Tegaserod inhibited SERT-, DAT-, and NET-mediated transport with IC50-values of
      11.7, 20.7, and 3.2 micromol/l, respectively, while 100 micromol/l estrone-3
      sulfate or taurocholic acid, used as negative controls, failed to inhibit hSERT
      mediated transport. Using Dixon plot analysis, inhibition kinetics yielded a non
      competitive type of inhibition with an apparent inhibition constant (Ki) of 3.1
      micromol/l for SERT-mediated 5-HT transport. CONCLUSION: In the present study we
      propose an additional mechanism of action for tegaserod as a serotonin uptake
      inhibitor. By inhibiting SERT and increasing local 5-HT concentrations in the gut
      wall, tegaserod might exert its prokinetic action via a synergism between 5-HT4
      agonism and low-affinity SERT inhibition.

PMID- 17510553
TI  - Cronkhite-Canada syndrome hamartomatous polyps are infiltrated with IgG4 plasma
      cells.

PMID- 17510554
TI  - Protein-losing gastroenteropathy and gastric polyps: successful treatment by
      Helicobacter pylori eradication.

PMID- 17510555
TI  - Balloon-occluded retrograde transvenous obliteration for gastric varices with
      plural draining veins: effectiveness of coil embolization for collaterals.

PMID- 17510556
TI  - Protein-losing gastroenteropathy in a patient with pityriasis rubra pilaris.

PMID- 17510557
TI  - Activity budget and ranging patterns of Colobus vellerosus in forest fragments in
      central Ghana.
AB  - The forest fragments surrounding the 192-ha Boabeng-Fiema Monkey Sanctuary (BFMS)
      in central Ghana contain small populations of Colobus vellerosus. Data were
      collected on activity budget, ranging patterns and habitat use of 3 groups living
      in these small fragments in August-November 2003, and compared to 3 BFMS groups.
      Fragment groups spent less time moving and more time resting than BFMS groups.
      Home ranges of fragment groups tended to be smaller than those of BFMS groups.
      Fragment and BFMS groups used similarly sized trees. Comparisons of activity
      budget and ranging between fragments and the BFMS suggest that fragment habitat
      quality was sufficient to sustain current numbers. These behavioral trends are
      consistent with a concurrent study that we conducted investigating ecological
      quality in the same fragments.

PMID- 17510558
TI  - Postural sway during dual tasks in young and elderly adults.
AB  - BACKGROUND: Previous studies have shown that healthy young adults are able to
      decrease their standing postural sway when an additional postural visual task,
      such as reading, is performed. OBJECTIVE: In this study, we investigated postural
      sway during dual tasks in young and elderly adults. METHODS: Twelve healthy
      active elderly adults (aged 65-75 years) and 12 healthy young adults (aged 22-39
      years) participated in the study. The subjects performed different visual tasks
      while standing on a force plate. We varied the nature of the visual tasks
      (looking at a blank target versus a visual search task) and the distance of
      visual targets (near versus far). Center of pressure displacement obtained from
      the force plate data and kinematics of body segments obtained from a video
      analysis system were investigated. RESULTS: Both groups presented significantly
      larger postural sway in the mediolateral direction during the eyes-closed
      condition as compared with the eyes-open condition. In the anteroposterior
      direction, this effect was observed only for the elderly group. Both groups had
      the same percentage correct in counting letters, but the elderly adults were
      significantly slower as compared with the young adults. The amplitude of postural
      sway was greater for the elderly adults than for the young adults in all
      conditions. However, both the young and the elderly adults exhibited significant
      reductions in sway during performance of the search task relative to sway during
      viewing of a blank target. The sway was also reduced for both groups during
      viewing a near target when compared to a distant target. CONCLUSIONS: The results
      suggest that, despite the overall increase in postural sway with aging, subtle
      integration of visual information by the postural control system is not affected
      by aging. The present results support the idea that dual tasks do not necessarily
      lead to an increase in postural sway. This effect, found here in elderly adults,
      raises questions about widely held views in which age-related changes in postural
      sway are related to competition between postural control and other activities for
      central processing resources.

PMID- 17510559
TI  - 'In vitro' protective effect of a hydrophilic vitamin E analogue on the decrease
      in levels of elongation factor 2 in conditions of oxidative stress.
AB  - BACKGROUND: Protein synthesis is inhibited by oxidative stress. Among the
      possible causes of this inhibition are the modifications of elongation factor 2
      (eEF-2), the protein that catalyzes the translocation of the ribosome through
      mRNA. eEF-2 is extremely sensitive to oxidative stress caused mainly by lipid
      peroxidant compounds such as cumene hydroperoxide (CH). OBJECTIVE: The purpose of
      this study was to determine whether the antioxidant Trolox prevents the effect of
      CH on the levels of hepatic eEF-2. METHODS: The effect was determined in liver
      homogenates treated with both compounds. Lipid peroxides and carbonyl content
      were also measured. RESULTS: The results show that Trolox at certain doses
      prevents the decrease in the level of eEF-2 caused by CH. CONCLUSION: Under
      oxidative stress circumstances, vitamin E can prevent the effect of oxidations on
      relevant biological processes such as protein synthesis.

PMID- 17510560
TI  - Chronic anemia and thrombocytosis as the initial presentation of Still's disease
      in an elderly patient.
AB  - Still's disease is very rare in elderly patients. We report a case of Still's
      disease in an elderly patient that had an atypical initial presentation. A 76
      year-old woman developed unexplained chronic anemia and thrombocytosis. Three
      years later she had acute onset of high fever, arthritis, maculopapular rash,
      pleuritic chest pain, abdominal pain, lymphadenopathy and elevated erythrocyte
      sedimentation rate. Rheumatoid factor and antinuclear antibodies were negative.
      She responded favorably to prednisone and methotrexate treatment. Anemia and
      thrombocytosis as well as Still's disease manifestations resolved.

PMID- 17510561
TI  - Effect of high-salt diet on vascular relaxation and oxidative stress in
      mesenteric resistance arteries.
AB  - This study tested the hypothesis that superoxide levels are elevated in isolated
      mesenteric resistance arteries (100-300 microm) from rats fed a short-term high
      salt (HS) diet (4% NaCl for 3 days) compared to controls fed a low-salt (LS) diet
      (0.4% NaCl). Vascular relaxation induced by the superoxide dismutase mimetic
      tempol (4-hydroxytetramethylpiperidine-1-oxyl), the NADPH oxidase inhibitor
      apocynin and the xanthine/xanthine oxidase inhibitor oxypurinol was significantly
      larger in mesenteric arteries from animals fed HS diet compared to arteries from
      animals fed LS diet. Basal superoxide levels assessed via dihydroethidine (DHE)
      fluorescence were significantly elevated in arteries from rats fed HS diet, and
      were reduced by tempol, apocynin and oxypurinol, but not by L-NAME. Basal and
      methacholine-induced NO production (assessed by DAF-2T fluorescence) was
      significantly reduced in arteries from rats fed HS diet versus arteries from rats
      on LS diet. Impaired methacholine-induced NO release and vascular relaxation were
      restored by tempol and apocynin, but not by oxypurinol. These data suggest that
      the elevated production of superoxide by NADPH oxidase and xanthine/xanthine
      oxidase contribute to elevated basal superoxide levels, reduced NO release and
      impaired vascular relaxation in mesenteric resistance arteries of rats fed HS
      diet.

PMID- 17510562
TI  - Can modulation of mammary gland development by dietary factors support breast
      cancer prevention?
AB  - Breast cancer continues to be a major challenge for public health, since it is
      the most common cancer of women in the Western world, and its prevalence is still
      increasing. In order to achieve better results in the prevention and treatment of
      breast cancer it is crucial to identify the mechanisms behind its initiation,
      i.e. the changes and deviations that have occurred in the mammary gland growth.
      It has long been known that a woman's reproductive history is the strongest
      breast cancer risk factor if genetic background and age are excluded. The
      reproductive hormones, and the timing of events leading to changes in these
      hormones, and consequently, in the mammary gland, are the most important players.
      However, it has become obvious that dietary components may also contribute to
      breast cancer risk through their effects on the mammary gland. The past few years
      have added important information to our knowledge of the mechanisms behind breast
      cancer initiation at the level of target cells (mammary stem cells) and gene
      expression (genetic 'fingerprint' associated with persistent pregnancy-induced
      protection against breast cancer), as well as of the effects of certain dietary
      factors (steroid action modulators). These results and their links to breast
      cancer initiation and progression will be discussed.

PMID- 17510563
TI  - Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4
      (chemokine ligand-receptor) interaction in cancer cell migration.
AB  - Chemokines are small, secreted proteins and are now the largest known cytokine
      family. They mediate their effects through a family of G-protein-coupled
      receptors and were initially recognized for their ability to act as chemo
      attractants and activators of specific types of leucocytes in a variety of immune
      and inflammatory responses. However, during the past 5 years there has been a
      chemokine revolution in cancer and all scientists and clinicians in oncology
      related fields are now aware of their crucial role at all stages of neoplastic
      transformation and progression. The most important chemokine ligand-receptor
      interaction is that of the CXCL12 (stromal cell-derived factor-1, SDF-1) ligand
      with its exclusive receptor CXCR4; this interaction has a pivotal role in the
      directional migration of cancer cells during the metastatic process. This has
      been demonstrated by in vitro and in vivo experiments in addition to
      retrospective clinical studies. These findings have exciting implications in the
      field of cancer therapeutics, with several small molecule CXCR4 antagonists
      having been developed, which may provide clinical benefit in the therapy of
      cancer metastasis. Interestingly, it is likely that the effect of the anti-HER2
      antibody [trastuzumab (Herceptin] in breast cancer involves downregulation of the
      CXCR4 receptor. Unfortunately, a major problem is that chemokine receptors are
      expressed in other cells within the body, particularly those of the immune system
      and it is not clear what effects long-term CXCR4 antagonism could have on innate
      and adaptive immunity. However, there is little doubt that the great strides made
      in elucidating the complex relationship between chemokines and their role in
      cancer will soon translate into significant survival benefits for patients.

PMID- 17510564
TI  - Evaluation of CD31 (PECAM-1) expression using tissue microarray in patients with
      renal cell carcinoma.
AB  - Intratumoural microvessel density (MVD) has prognostic significance in selected
      neoplasms. To evaluate the prognostic information of MVD in renal cell carcinoma
      (RCC) we assessed the immunohistochemical expression of CD31 in 208 tumours using
      the tissue microarray technique. The expression was related to tumour cell type,
      TNM stage, nuclear grade and survival. CD31 expression was significantly (p <
      0.001) higher in 167 conventional RCCs (clear cell) compared to 28 papillary
      RCCs. In conventional RCC, CD31 expression was inversely correlated to TNM stage
      (p = 0.024) and nuclear grade (p = 0.010). To evaluate the impact of CD31
      expression on tumour-specific survival, the conventional RCC tumours were
      subdivided into quartiles according to the CD31 expression. In univariate
      analysis, patients with tumours in the quartile with the highest expression had a
      more favourable prognosis (p = 0.01) compared to those with lower CD31
      expression. A multivariate analysis of prognostic factors in conventional RCC
      showed that TNM stage and nuclear grade were independent predictors of prognosis,
      but CD31 expression did not add further prognostic information.

PMID- 17510566
TI  - Response to "A middle range theory for generative quality of life for the
      elderly".

PMID- 17510568
TI  - Women in young and mid-adulthood: theory advancement and retroduction.
AB  - This research explicated developmental constructs in women at the Age 30 and Age
      50 Transitions. Fifty-five women participated in field study conducted over 16
      years. Data collection strategies included interviews, focus groups, a life
      history technique, participant observation, and electronic participation.
      Individual and cohort effects were observed using interpretative analysis
      techniques. Concepts from Erikson's theory of psychosocial development were used
      for theoretical retroduction. The psychosocial tasks of the Age 30 Transition are
      identity confusion and intimacy as well as generativity. The challenge of the Age
      50 Transition is to continue the tasks of intimacy and generativity and add
      integrity.

PMID- 17510569
TI  - Handling the "people who are trying to get to you": incidents with troublesome
      visitors reported by older women living alone.
AB  - Older women have been viewed as vulnerable and fearful of crime, but little is
      known about how they try to reduce the risk of intrusion relative to encounters
      with troublesome visitors at home. During a phenomenological study of the home
      care experience, 6 women (aged 82-93 years) reported such an encounter with
      someone they knew. Our purpose was to describe intentions relative to encounters
      and the relevant personal-social context. Because the women were trying to keep a
      particular person at arm's length, the new concept of focused fear was proposed.
      Six contextual elements were discerned and understood as facets of vulnerability.

PMID- 17510570
TI  - A qualitative study of menopause among women with disabilities.
AB  - Few studies have examined the way women with disabilities understand and make
      decisions regarding menopause. This report is a qualitative descriptive study
      detailing how women with varying mobility impairments view the menopausal
      transition. Nineteen women aged 42 to 64 years were interviewed regarding their
      menopausal experiences. Results described their experiences as minority groups of
      women with disabilities using a women's ways of knowing framework. Overall, most
      women described menopause as a back burner issue, but maintained the need for
      accurate information from which to make informed decisions that might impact
      future health and functional outcomes.

PMID- 17510571
TI  - Mothers' understanding of their infants in the context of an internal working
      model of caregiving.
AB  - Exploration of mothers' understanding of their infants was guided by the concept
      of internal working model of caregiving, which includes relationship-relevant
      expectations and intentions. Twenty-nine mothers of healthy, term infants
      participated in semistructured interviews concerning actual and hypothetical
      caregiving episodes. Expectations and intentions were each rated with an ordinal
      rating (1-6) that qualified adaptiveness or attunement. On average, mothers
      viewed their infants as having their own agendas and intended to accommodate them
      within limits. Further specification of expectations and intentions and
      exploration of conditions that contribute to ordinal types could help researchers
      and clinicians tailor interventions supportive of maternal development.

PMID- 17510572
TI  - Relationship dynamics: understanding married women's mental health.
AB  - Because married women are at increased risk for depression, it is important to
      identify factors that explain women's experience of mental health. Bowen Theory
      was used to examine differentiation of self and relationship factors, such as
      need fulfillment, as predictors of married woman's psychologic well-being.
      Multiple regression demonstrated that a significant proportion of women's well
      being was attributable to interdependence in the marriage and the perception that
      interactional, emotional, and sexual needs were being met. Clinicians can support
      positive mental health outcomes through early identification of women who may be
      at risk for psychologic distress and referral for individual or marital
      counseling.

PMID- 17510573
TI  - Problems with preparing food reported by frail older women living alone at home.
AB  - Although nutritional risk is a critical health concern for older persons, there
      are few data about day-to-day problems with nutrition-related tasks. Such data
      were reported by 18 frail women during a longitudinal descriptive
      phenomenological study of the home care experience. Six problems were understood
      as elements of the life-world of older women, including having trouble figuring
      out what to fix, having trouble getting the food cooked right, and struggling
      with moving and standing while cooking. The results suggest topics for research
      and underscore the need for partnership between frail older women and helpers
      relative to food preparation.

PMID- 17510574
TI  - Women's self-care agency to manage urinary incontinence: the impact of nursing
      agency and body experience.
AB  - BACKGROUND: Women with urinary incontinence (UI) report that the disease
      negatively impacts their quality of life but, paradoxically, under-report
      symptoms. METHOD: A predictive model using Orem's self-care deficit theory was
      developed exploring the effect of body experience on self-care agency to manage
      UI. A sample of postmenopausal women was drawn from a larger trial. Structural
      equation modeling was used to test the proposed model. RESULTS: Minor
      modification of the model produced a well-fitting model (chi(9) = 3.20, P = .96,
      n = 235). Results supported the positive effect of nursing agency on self-care
      agency. CONCLUSION: Group education about UI may increase self-care agency in
      postmenopausal women.

PMID- 17510576
TI  - Assessing cultural appropriateness of three translated cancer-related fatigue
      instruments.
AB  - The purpose of this study was to evaluate the cultural appropriateness (ie,
      semantic equivalence, content equivalence, and conceptual equivalence) of 3
      translated fatigue instruments (the Cancer Fatigue Scale, the Fatigue Symptom
      Inventory, and the Schwartz Cancer Fatigue Scale-revised) by using 2 phases: (a)
      establishment of semantic and content equivalencies by the rigorous process of
      translation and back-translation, and (b) evaluation of content equivalence and
      conceptual equivalence by testing on monolingual subjects with the translated
      fatigue scales and a questionnaire with fatigue terms list and open-ended
      questions. Convenience sampling was used to recruit subjects at a chemotherapy
      treatment center for outpatients in Taiwan. The results indicated that the
      content in the 3 scales were relevant to the experience of fatigue among
      Taiwanese from the view of patients, but only the fatigue domains in the Cancer
      Fatigue Scale-Chinese version was similar to the original construct based on the
      exploratory factor analysis. However, the results for examining the content
      equivalencies by the fatigue terms list showed that only 4 items in the list were
      used to describe fatigue by more than 50% of the patients. Therefore, the
      contents of the chosen scales might not represent the whole concept of fatigue in
      Taiwan. Exploration of the content and construct of fatigue in Taiwan and further
      testing of the translated scales are recommended. In addition, the result in this
      study is helpful for clinical nurses to understand expressions of fatigue in
      cancer patients within the Chinese culture but the meaning of fatigue still needs
      to be further explored.

PMID- 17510577
TI  - Individual psychosocial support for breast cancer patients: a randomized study of
      nurse versus psychologist interventions and standard care.
AB  - In a prospective, randomized study, an individual psychosocial support
      intervention performed by specially trained oncology nurses, or psychologists,
      were compared with standard care. Consecutive primary breast cancer patients
      about to start adjuvant therapy (n = 179) were included. Data were supplied by
      the questionnaires European Organisation for Research and Treatment of Cancer
      Quality of Life Study Group Core Quality of life questionnaire with 30 questions
      (EORTC QLQ-C30) and Breast Cancer Module with 23 questions (BR23), the Hospital
      Anxiety and Depression Scale, Spielberger's State-Trait Anxiety Inventory, and
      the Impact of Event Scale before randomization and 1, 3, and 6 months later.
      Patient files provided data on utilization of psychosocial support offered in
      routine care. Global quality of life/health status, nausea and vomiting, and
      systemic therapy side effects were the subscales showing significant Group by
      Time interactions, favoring the interventions. Intervention groups improved
      statistically significantly more than the standard care group regarding insomnia,
      dyspnea, and financial difficulties. Nurse patients experienced less intrusion
      compared with the standard care group. All groups showed statistically and
      clinically significant improvements with time on several subscales. The
      intervention groups, however, improved to a greater extent. Fewer patients in the
      intervention groups used psychosocial hospital support compared with the standard
      care group. In conclusion, psychosocial support by specially trained nurses using
      techniques derived from cognitive behavioral therapy is beneficial for breast
      cancer patients and may be a realistic alternative in routine cancer care.

PMID- 17510578
TI  - Reliability and validity of the Champion's Health Belief Model Scale among
      Lithuanian women.
AB  - The rates of incidence and mortality of breast cancer in Lithuania are increasing
      and, although a mammography screening program is present, attendance rate is
      rather low. The aim of this study was to assess the reliability and validity of
      the revised Champion's Health Belief Model Scale in measuring Lithuanian women's
      beliefs about breast cancer and screening. The data were collected from 350
      female citizens 40 to 69 years old living in the urban district, and having no
      history of breast cancer and no mammogram in the past. The Champion's Health
      Belief Model Scale was translated to Lithuanian, validated by professional
      judges, back-translated to English, and pretested. Analysis included descriptive
      statistics of demographic data, content and construct validity, using factorial
      analysis, internal consistency, reliability estimates, and using the Cronbach
      alpha technique. Factor analysis yielded 11 factors related to breast self
      examination and 7 factors to mammography. All items on each factor were from the
      same construct. The motivation subscale split into the items related to general
      concern about health and preventive health practices. Alpha coefficients ranged
      from.61 to.92. Only the mammography barrier item "having a routine mammogram or x
      ray of the breast would make me worry about breast cancer" loaded as a separate
      factor in factor analysis and showed low correlation with other subscale items.
      Participants in the mammography group showed lower perceived susceptibility in 3
      items and perceived severity in 1 item. They reported having not enough privacy
      for breast self-examination, and were less confident in their skills to perform
      it. However, the women in the nonparticipating mammography group showed lower
      results in one benefit-mammogram item, and had more barriers for mammography in
      comparison with the participating group. We conclude that the Champion's Health
      Belief Model Scale is a reliable and valid tool for measuring the screening
      beliefs toward breast cancer among Lithuanian women. The model gave better
      results when the motivation items were subdivided into subscales related to
      general concern about health and related to preventive health practices and were
      considered separately. Mammography barrier item "having a routine mammogram or x
      ray of the breast would make me worry about breast cancer" was deleted from the
      Lithuanian Champion's Health Belief Model Scale.

PMID- 17510579
TI  - The Health Utilities Index 3 invalidated when completed by nurses for pediatric
      oncology patients.
AB  - When health-related quality of life instruments developed for and validated in 1
      respondent group are completed by a different respondent group, findings could be
      invalid. The purpose of this study was to summarize the instrument outcomes when
      a widely used health-related quality of life instrument (the Health Utilities
      Index 3 [HUI3]) created from a population-based strategy was completed by
      pediatric oncology nurses for their patients during cancer treatment. Fifty-four
      nurses completed the HUI3 a total of 261 times at 1 to 3 sequential data points
      (106, 94, and 61, respectively) for pediatric patients who were enrolled on a
      frontline therapeutic clinical trial for acute lymphoblastic leukemia. Data were
      collected at 2 children's hospitals. HUI3 scores could not be calculated for 52%
      to 61% of the nurse reports at each of the 3 data points because of nurses' use
      of the "do not know" response option. Missing data of this proportion indicate
      that the nurse serving as a proxy rater independent of directly soliciting
      responses from the patient will not be able to rate certain attributes of the
      HUI3 more than half of the time despite having ongoing familiarity with the
      patient. Because of this, use of the HUI3 by nurse proxies for patients with
      pediatric acute lymphoblastic leukemia is not recommended.

PMID- 17510580
TI  - Perceptions of colon cancer screening by stage of screening test adoption.
AB  - Colorectal cancer remains the second leading cause of cancer death in the United
      States. To fully realize the benefits of early detection of colorectal cancer,
      screening rates must improve. This study assessed differences in beliefs (from
      the Health Belief Model) by stage of screening behavior adoption (based on the
      Transtheoretical Model of Change) as a foundation for intervention development.
      More people were in the precontemplation stage (not thinking about having the
      screening test) for fecal occult blood test and sigmoidoscopy versus
      contemplation (thinking about having the test) or action (adherent with
      screening). Those in precontemplation stage for fecal occult blood test had lower
      perceived risk than those in contemplation, lower perceived benefits than those
      in action, and higher barriers than both those in contemplation and those in
      action. For sigmoidoscopy stage of readiness, again, precontemplators had lower
      perceived risk and self-efficacy than contemplators and higher barriers than both
      contemplators and actors. Given the popularity of the transtheoretical model and
      the success of stage-based interventions to increase other cancer screening,
      especially mammography, we should begin to translate such effective interventions
      to colorectal cancer screening. As such, this study is one of very few to
      quantify beliefs across stages of colorectal cancer and identify significant
      differences across stages, laying the foundation for the development and testing
      of stage-based interventions.

PMID- 17510581
TI  - Self-efficacy and quality of life among stoma patients in Hong Kong.
AB  - Stoma patients are vulnerable to poor psychosocial health outcomes owing to the
      loss of an important bodily function and the distortion of their self-image. We
      used a cross-sectional, descriptive, and correlational design to investigate the
      relationship between self-efficacy and quality of life of stoma patients in Hong
      Kong and to examine the association between self-efficacy and stoma patients'
      sociodemographic characteristics. Using a convenience sampling method, 96
      patients (mean age, 64 years) were recruited from 2 acute hospitals. Significant
      correlations were found between the Chinese Stoma Self-efficacy Scale and the
      Chinese Short-Form Health Survey 36 subscale scores (from r = 0.21, P = .039, to
      r = 0.59, P < .001). Significant positive correlations were also found between
      the 2 Chinese Stoma Self-efficacy subscales and all 8 of the Chinese Short-Form
      Health Survey 36 subscales. The results indicated that the self-efficacy and
      quality of life of stoma patients were correlated. Based on this study's results,
      self-efficacy is an important factor to consider in the provision of care to
      stoma patients. Specific interventions to enhance self-efficacy also need to be
      evaluated for their impact on the quality of life of stoma patients.

PMID- 17510582
TI  - Breast cancer diagnosis and its treatment affecting the self: a meta-synthesis.
AB  - There has been a great deal of qualitative research conducted that has examined
      the impact of breast cancer on the Self, however, there has been little effort to
      analyze these findings from a meta-perspective. This study sought to fill this
      gap by conducting a meta-synthesis of the qualitative research on breast cancer
      and its treatments affecting the Self. Meta-method and meta-synthesis techniques
      were used to integrate findings across 30 qualitative research reports conducted
      between 1990 and 2003 with a total of 795 women, from several different
      countries.The fusions identified from this meta-synthesis revealed 4 aspects of
      the Self affected by the diagnosis of breast cancer and its treatment: awareness
      of their own mortality, living with an uncertain certainty, attachment
      validation, and redefinition of Self. These findings were validated through use
      of a comparison study. The women adapt to being a breast cancer patient;
      redefining their lives and their self. This study highlights the existential
      process that women of many cultures move through as they incorporate the meaning
      of breast cancer into their lives. Nurses who are aware of these processes are
      better able to link women with resources to help them in their adaptation to
      living with breast cancer.

PMID- 17510584
TI  - Development of the Comprehensive Inventory of Functioning-Cancer.
AB  - The Comprehensive Inventory of Functioning-Cancer (CIF-CA) was developed to
      measure actual and desired functional status in women with cancer. CIF-CA items
      were taken from the Inventory of Functional Status-Cancer, which measures only
      actual performance of usual activities. Six CIF-CA subscales measure the extent
      to which women perform usual personal care, family care, household, social,
      community, and occupational activities following diagnosis of cancer (actual
      functional status) and the level at which they wish to perform those activities
      (desired functional status). Reliability and construct validity estimates were
      obtained using a sample of 190 women with breast, lung, or colon cancer. Internal
      consistency reliability using average correlations for subscale item to subscale
      total scores ranged from 0.68 to 0.93 for actual functional status and from 0.61
      to 0.85 for desired functional status. Internal consistency reliability
      coefficients for subscale to total CIF-CA scores ranged from 0.46 to 0.86 for
      actual functional status and from 0.62 to 0.83 for desired functional status.
      Initial construct validity coefficients, using subscale to subscale scores,
      ranged from 0.10 to 0.61 for actual functional status and from 0.33 to 0.62 for
      desired functional status. The data support continued development of the CIF-CA.

PMID- 17510585
TI  - Breast cancer screening for Korean women must consider traditional risks as well
      as two genetic risk factors: genetic polymorphisms and inheritable gene
      mutations.
AB  - Asian women worldwide have increasing rates of breast cancer due to acculturation
      which may be altering, gene to gene and/or, genetic and environmental
      interactions at the cellular level. The purpose of this integrative review is to
      alert nurses and physicians to rising rates of breast cancer among Korean women
      and to a need for breast health screening programs in the United States that are
      more culturally responsive and attentive to the effects of acculturation and
      genetic risk factors. A comprehensive review of the English and Korean literature
      pertaining to rising incidence of breast cancer among Korean women in their
      homeland and in the United States is retraced since 1983. Korean women in Korea
      and in the United States face similar barriers to cancer screening services.
      Korean women need knowledge about the effect of acculturation on breast cancer
      risk and patterns of familial inheritance of breast cancer. Screening is
      especially important among younger women (younger than age 35), those with a
      strong family history, and women in community settings where acculturation has
      its greatest impact. Nurse clinicians and researchers who aim to improve breast
      cancer screening among minority women must pay closer attention to these risk
      factors and design culturally competent services and evaluation research. In the
      United States and Korea, Korean nurses are needed to specialize in breast cancer
      screening as well as cancer genetic risk assessment and genetic counseling.

PMID- 17510586
TI  - Development and testing of a scale to measure caregiving load in caregivers of
      cancer patients in Taiwan, the care task scale-cancer.
AB  - The purpose of this study was to develop and test an instrument to measure care
      tasks for Taiwanese spouse caregivers of cancer patients. A 37-item Care Task
      Scale-Cancer (CTS-C) was developed using both quantitative and qualitative
      approaches. The reliability and validity of the CTS-C was tested on a convenience
      sample of 150 spouse caregivers caring for patients with breast cancer, head neck
      cancer, or esophageal cancer. Factor analysis showed that the CTS-C had 4
      underlying factors (subscales): (1) accompany patient and monitor care (12
      items), (2) substitutive care for social and general affairs (12 items), (3)
      communication and emotional care (9 items), and (4) mobility maintenance care (4
      items). These 4 factors explained 52.3% of the total variance. Cronbach alpha
      coefficients for these 4 subscales ranged from .83 to .88. Test-retest
      coefficients (r) ranged from 0.92 to 0.94. The construct validity of this scale
      was supported by demonstrating a negative correlation between CTS-C scores
      (demand, difficulty, and caregiving load) and functional performance status, and
      positive correlations with caregiver burden and symptom distress. These results
      showed satisfactory validity and reliability for the CTS-C.

PMID- 17510588
TI  - The ovarian cancer journey of families the first postdiagnostic year.
AB  - Ovarian cancer care has shifted from hospitals to families and has resulted in an
      unanticipated cancer journey as survivability for women so diagnosed has
      increased. This research investigated the impact of this responsibility on
      selected aspects of family functioning. Eighteen families participated in 5
      family research visitations over the first postdiagnostic year. Quantitative data
      were obtained on socioemotional responses, behaviors, and coping strategies.
      Accounts of family experiences were recorded in field notes and narrative
      descriptions. Descriptive and narrative analyses were used. Subject families were
      strong and experienced a mosaic of variations in socioemotional and behavioral
      responses. Coping responses relied primarily on reframing and spiritual support.
      Families had hope and optimism and received socioemotional support from kin and
      friends. Response patterns consisted of providing support and care to sick
      members; making transformative changes in family structures, roles, and
      functions; reorganizing daily living experiences to integrate new situations; and
      minimizing gaps between professional and familial perspectives and realities. On
      this journey, families could have used timely knowledge and professional
      expertise to plan care, balance illness and family needs, restructure roles and
      responsibilities, maintain family unity, and give meaning and wholeness to
      experiences. Family-based oncology nursing is essential for family well-being and
      growth.

PMID- 17510589
TI  - Quality of life of Chinese patients with ovarian malignancies during chemotherapy
      under condition of no recurrence.
AB  - The purpose of this study was to describe the quality of life of patients with
      ovarian malignancies during chemotherapy under condition of no recurrence and to
      explore changes in quality of life during chemotherapy and factors associated
      with quality of life. It was a cohort study during treatment. Quality of life of
      75 patients with ovarian malignancies at baseline, reduced to 63 and 61 patients
      at later points, was assessed by the Functional Assessment of Cancer Therapy
      Ovarian scale in the gynecologic wards of the Obstetrics and Gynecology Hospital
      affiliated to Fu Dan University within 1 to 2 days after the second, fourth, and
      sixth cycles of chemotherapy. During chemotherapy, under condition of no
      recurrence, the overall quality of life was at the middle or upper level and
      improved significantly over time (P = .044). There were significant improvements
      in physical well-being and additional concerns, whereas there was significant
      deterioration in social well-being. Emotional and functional well-being showed a
      trend toward improvement (not statistically significant). The relationship with
      doctors showed a significant difference between the first time point and each of
      the other two. Economic condition and intrafamily support were key factors for
      predicting the quality of life of these patients in all assessments. These
      findings give insights into the quality of life of women with ovarian cancer
      during chemotherapy and imply that nurses and other medical professionals should
      provide continuing support to them in accordance with their needs. Furthermore,
      nurses should help prevent them from social isolation as a consequence of their
      illness and treatment and acknowledge family members as a major support resource.

PMID- 17510590
TI  - Objective documentation of traumatic brain injury subsequent to mild head trauma:
      multimodal brain imaging with MEG, SPECT, and MRI.
AB  - OBJECTIVE: To determine to what extent magnetic resonance imaging (MRI), single
      photon emission computed tomography (SPECT), and magnetoencephalography (MEG) can
      provide objective evidence of brain injury in adult patients with persistent (>1
      year) postconcussive symptoms following mild blunt head trauma. DESIGN: A
      retrospective and blind review of imaging data with respect to the presence of
      specific somatic, psychiatric, and cognitive complaints. SETTING/PARTICIPANTS:
      Thirty complete data sets (with MRI, SPECT, MEG, and neuropsychological testing
      results) were collected between 1994 and 2000 from the MEG programs at the
      Albuquerque VAMC and the University of Utah. MAIN OUTCOME MEASURES: MRI data were
      evaluated for focal and diffuse structural abnormalities, SPECT data for regions
      of hypoperfusion, and resting MEG data for abnormal dipolar slow wave activity
      (DSWA) and epileptiform transients. RESULTS: Structural MRI was abnormal for 4
      patients. SPECT showed regions of hypoperfusion in 12 patients, while MEG showed
      abnormal activity in 19 patients. None of the imaging methods produced findings
      statistically associated with postconcussive psychiatric symptoms. A significant
      association was found between basal ganglia hypoperfusion and postconcussive
      headaches. For patients with cognitive complaints, abnormalities were more likely
      to be detected by MEG (86%) than either SPECT (40%) or MRI (18%) (P<.01). MEG
      also revealed significant (P<.01) associations between temporal lobe DSWA and
      memory problems, parietal DSWA and attention problems, and frontal DSWA and
      problems in executive function. CONCLUSIONS: Functional brain imaging data
      collected in a resting state can provide objective evidence of brain injury in
      mild blunt head trauma patients with persistent postconcussive somatic and/or
      cognitive symptoms. MEG proved to be particularly informative for patients with
      cognitive symptoms.

PMID- 17510591
TI  - Self-assessment of impairment, impaired self-awareness, and depression after
      traumatic brain injury.
AB  - OBJECTIVE: To identify patient features associated with early and late depression
      after traumatic brain injury (TBI). PARTICIPANTS: 3 clinical trauma groups (mild
      TBI, moderate-severe TBI, orthopedic injury) and their significant others.
      MEASURES: Preinjury: age, education, substance abuse, and psychiatric history;
      Injury severity: classification using Glasgow Coma Scale and cranial CT scan,
      posttraumatic amnesia; Early impairment: Neurobehavioral Functioning Inventory
      (NFI), Impaired Self-Awareness (ISA); Social and family support: Multidimensional
      Scale of Perceived Social Support, Family Assessment Device; Depression: NFI
      Depression Scale. METHOD: Regression analyses of predictor variables on early and
      late measures of depression. RESULTS: Depression rates did not differ among the 3
      trauma groups. Preinjury level of education, previous psychiatric history, and
      perceived level of social support explained a small portion of the variance in
      depressive symptoms. Patients' self-assessment of their impairment at discharge
      was most strongly correlated with both early and late depression. ISA was
      associated with reduced self-report of depressive symptoms. However, when those
      with ISA were excluded from the analysis, self-assessment of impairment remained
      strongly associated with depression. CONCLUSIONS: Patients' self-assessment of
      impairment is strongly associated with early and late depression. Presence and
      severity of TBI does not appear to play a direct role in depression but does
      appear related to ISA, which serves as a barrier to the development of
      depression. Focusing on impairment appears to be a cardinal feature of depression
      in both patients with TBI and an orthopedic trauma group.

PMID- 17510592
TI  - Feasibility of a skills-based substance abuse prevention program following
      traumatic brain injury.
AB  - OBJECTIVE: To demonstrate the feasibility of a skills-based substance abuse
      prevention counseling program in a community setting for adults who sustained
      traumatic brain injury. PARTICIPANTS: Convenience sample of 117 participants
      (mean age=35 years) with preinjury history of alcohol or other drug use.
      Intervention group participants (n=36) from 3 vocational rehabilitation programs;
      a no-intervention comparison group (n=81) from an outpatient rehabilitation
      service. INTERVENTION: 12 individual counseling sessions featuring skills-based
      intervention. MAIN OUTCOME MEASURES: Changes in self-reported alcohol and other
      drug use, coping skillfulness, affect, and employment status from baseline to 9
      months postintervention. RESULTS: Significant differences were noted at baseline
      for the intervention and comparison groups on ethnicity, time postinjury, marital
      status, and employment (P<.05). At the 9-month follow-up, the intervention group
      participants achieved a statistically significant decrease in alcohol and drug
      use (P<.05), increase in coping skillfulness (P<.01), and increased likelihood of
      maintaining employment (P<.01) relative to the comparison group. Controlling for
      baseline-adjusted means for the intervention and comparison groups, a
      statistically significant group difference in adjusted change was noted; the
      intervention group participants reported lower negative affect at the 9-month
      follow-up assessment (P<.05). CONCLUSIONS: A skills-based intervention provides a
      promising approach to promoting abstinence from all substances and increasing
      readiness for employment for adults with traumatic brain injuries in outpatient
      settings.

PMID- 17510593
TI  - Agitation in acquired brain injury: impact on acute rehabilitation therapies.
AB  - OBJECTIVE: To examine the nature of agitation in patients with brain injury and
      quantify the relation between agitation and patient progress in rehabilitation.
      DESIGN: Cross-sectional, correlational. SETTING: Urban, inpatient rehabilitation
      facility in the midwestern United States. PARTICIPANTS: Sixty-nine patients with
      acquired brain injury admitted to an acute rehabilitation hospital. MAIN OUTCOME
      MEASURES: Therapy Engagement using the Rehabilitation Therapy Engagement Scale;
      Functional Status using the Functional Independence Measure. RESULTS: Agitated
      behavior was inversely associated with engagement in rehabilitation therapy even
      after controlling for injury severity. Engagement in therapy mediated the
      relation between agitated behavior and progress in rehabilitation as assessed
      using a Functional Independence Measure efficiency ratio. CONCLUSIONS: Progress
      in acute brain injury rehabilitation appears to be meaningfully influenced by the
      complex interplay among injury severity, agitation, and engagement. The findings
      are consistent with a theoretical model, suggesting that agitated patients make
      less progress in rehabilitation not only because of greater injury severity but
      also because agitation disrupts engagement in rehabilitation therapies. Multiple
      clinical purposes may be better served by measuring behavioral excess on a
      continuum than in a dichotomous fashion.

PMID- 17510594
TI  - Patterns and predictors of swallowing resolution following adult traumatic brain
      injury.
AB  - OBJECTIVE: To examine the patterns of swallowing resolution and outcomes of
      traumatic brain injury (TBI) patients in an acute care setting and document the
      risk factors or predictors of resolution of swallowing function. PARTICIPANTS:
      117 consecutive TBI patients who had received speech pathology intervention for
      dysphagia during acute postinjury care. MAIN OUTCOME MEASURE: Temporal measures
      relating to pattern of resolution of dysphagia postinjury. RESULTS: 75% of
      patients were assessed by 2 weeks postinjury, commenced oral intake by 17 days,
      and ceased supplementation by 3 weeks. By an average of 22 days after admission,
      47% had progressed to normal-consistency diet and fluids. Duration to the first
      swallowing assessment was a predictor for achieving total oral intake and
      returning to normal intake. There was some preliminary support for severity of CT
      data and presence/absence of a tracheostomy as predictors for return to normal
      intake. CONCLUSION: The current data document the natural history of swallowing
      resolution and proposes prognostic factors for patients with impaired swallowing
      following TBI. Establishing clinical parameters that can help predict patterns of
      swallowing resolution over the course of acute care admission may greatly assist
      inpatient management and discharge/rehabilitation planning.

PMID- 17510595
TI  - Delineating communication impairments associated with mild traumatic brain
      injury: a case report.
AB  - BACKGROUND: Mild traumatic brain injury (mTBI) without frank neurological
      disturbance has been linked to persistent physical, cognitive, and affective
      disturbances in some cases. The cognitive sequelae of this syndrome represent the
      most frequently studied symptoms, yet the legacy of such injuries on
      communicative functions remains largely undetermined. METHODS: A detailed
      language profile of a 19-year-old woman, 1 year 10 months following mTBI is
      compared with a matched normative cohort of 10 participants with nonneurological
      impairment. RESULTS: Deficits in attention, lexical access, complex lexical
      semantic manipulation, response monitoring, and organization were revealed as a
      consequence of mTBI. CONCLUSIONS: This profile provides support for hypotheses
      pertaining to neuronal fallout mechanisms within the frontal lobes as a
      consequence of mild neurological insult.

PMID- 17510596
TI  - Using interactive multimedia to teach parent advocacy skills: an exploratory
      study.
AB  - OBJECTIVE: To examine the efficacy of Brain Injury Partners: Advocacy Skills for
      Parents, an interactive multimedia intervention that provides training in
      educational advocacy skills for parents of children with traumatic brain injury
      (TBI). DESIGN: Randomized trial, with participants assigned to treatment (Brain
      Injury Partners CD-ROM) or control (alternate CD-ROM) conditions. MAIN OUTCOME
      MEASURES: Knowledge; skill application; and attitude, behavioral intention, and
      self-efficacy to use key advocacy skills. PARTICIPANTS: Thirty-one parents of
      children with TBI. RESULTS: The Brain Injury Partners group reported higher
      postintervention adjusted means for application, knowledge, and attitudes scale
      scores than did the control group. CONCLUSIONS: The results demonstrate the
      utility of a computer-delivered intervention for training parents in key skills
      for communicating with school personnel.

PMID- 17510598
TI  - The critical role of vascular endothelial growth factor in pulmonary vascular
      remodeling after lung injury.
AB  - The pulmonary vascular endothelial cell plays a crucial role in the regulation of
      the pulmonary vascular tone and in the maintenance of the barrier function and
      integrity of the alveolar-capillary membrane. It also plays a major role in
      coagulation, fibrinolysis, and angiogenesis and participates in inflammatory
      reactions. Vascular endothelial growth factor (VEGF) is a central growth and
      survival factor for the endothelial cell. Particularly high levels of VEGF are
      expressed in the lungs, reflecting the critical role of VEGF for lung development
      and structural integrity of the adult lung. Vascular endothelial growth factor
      exerts a variety of physiological and pathophysiological actions in the lung.
      Recent evidence suggests its involvement in the pathogenesis of lung diseases
      such as bronchopulmonary dysplasia, acute lung injury, emphysema, and pulmonary
      hypertension. To summarize the critical effects of VEGF on the pulmonary
      endothelial cell in the pathogenesis of these diseases, the purposes of this
      review are to (1) discuss the biological activities and intracellular signaling
      pathways of VEGF in the lung; (2) summarize the regulatory mechanisms involved in
      VEGF expression; (3)address the effects of VEGF on endothelial cells in hyperoxia
      induced and other forms of lung injury; (4) highlight the endothelial effects of
      VEGF in the pathogenesis of emphysema; and (5) explore the role of VEGF in the
      pathogenesis of pulmonary arterial hypertension.

PMID- 17510599
TI  - Cardiovascular effects of levosimendan in the early stages of endotoxemia.
AB  - Sepsis-associated myocardial depression is associated with calcium
      desensitization and adrenergic uncoupling. We conducted a prospective randomized
      investigation on the effects of the calcium sensitizer, levosimendan, on
      hemodynamics, myocardial blood flow, and myocardial lactate metabolism during
      porcine endotoxemia. Twelve pigs were studied. Oxygen consumption was measured by
      indirect calorimetry, and myocardial blood flow was measured by retrograde
      thermodilution. Pulmonary, arterial, and venous indwelling catheters allowed
      measurements of cardiac output, vascular pressures, and blood sampling. Fluids
      were given at an average of 15 mL . kg . h. After baseline measurements (0 min),
      an infusion of Escherichia coli LPS (2 microg . kg . min) was started in all
      animals. Beginning at 100 min, six animals received levosimendan (50 microg . kg
      . h), whereas six control animals received placebo. The study lasted for 300 min.
      All animals responded to endotoxin with pulmonary hypertension, a transient
      decrease in cardiac output, tachycardia, and systemic hypotension. Levosimendan
      infusion decreased systemic vascular resistance (P = 0.001), coronary vascular
      resistance (P = 0.004), and mean arterial (P < 0.001) and coronary perfusion
      pressures (P < 0.001), whereas pulmonary hypertension was unaffected. Heart rate
      progressively increased in both groups and was significantly higher in the
      levosimendan group (P = 0.048). Myocardial blood flow remained unchanged in both
      groups; however, 80 min after the start of levosimendan infusion, left
      ventricular myocardial hypoxia ensued, as evidenced by a negative myocardial
      lactate gradient (P = 0.01). Two control and five levosimendan animals died
      before the end of the study. Early administration of levosimendan during porcine
      endotoxemia increased heart rate, caused arterial vasodilation, and decreased
      coronary perfusion pressure, resulting in myocardial hypoxia.

PMID- 17510601
TI  - Role of the alternative pathway in the early complement activation following
      major trauma.
AB  - Complement activation has been reported after major trauma. However, little is
      known about the clinical relevance and the mechanisms of complement activation
      early after trauma. Therefore, the aim of this study was to measure complement
      activation, to identify the roles of injury severity and hypoperfusion, to
      determine the predominant activated pathway, and to identify the clinical
      significance of early complement activation in trauma patients. A total of 208
      adult trauma patients were enrolled in this prospective single-center cohort
      study of major trauma patients. Blood samples were obtained within 30 min after
      injury before any significant fluid resuscitation. Complement (C5b-9) was
      activated early after trauma, correlated with injury severity and tissue
      hypoperfusion, and was associated with increased mortality rate and with the
      development of organ failure such as acute lung injury and acute renal failure.
      The alternative pathway seems to be the predominant activated complement pathway
      early after trauma. However, the classical and/or the lectin pathway initiated
      complement activation because of the correlation between plasma levels of C4d and
      C3a/C5b-9. Finally, in patients with low C3a levels, C5b-9 levels correlated with
      plasma levels of prothrombin fragments 1 + 2, a marker of thrombin generation,
      suggesting additional C3-independent complement activation by thrombin after
      severe trauma. In summary, complement activation via its amplification by the
      alternative pathway is observed early after trauma and correlates with injury
      severity, tissue hypoperfusion, and worse clinical outcomes. Besides complement
      activation by the classical and/or lectin pathways, there is an independent
      association between thrombin generation and complement activation.

PMID- 17510602
TI  - Role of bacterial endotoxin in chronic heart failure: the gut of the matter.
AB  - Proinflammatory cytokines are now thought to play a key role in the
      pathophysiology of chronic heart failure, driving both symptomatic presentation
      and disease progression. We propose that this proinflammatory state, in turn, may
      be sustained through a chronic release of enterically derived bacterial
      endotoxin. Human trials have indicated that bacterial decontamination of the gut
      with concomitant decrease in lipopolysaccharide (LPS) has a positive outcome on
      heart disease patients. Antiendotoxin antibodies may thus represent therapeutic
      agents in this setting. Previously, antiendotoxin antibodies were targeted to the
      inner hydrophobic lipid A moiety of endotoxin in an attempt to neutralize its
      toxicity. These antibodies failed because they lacked specificity and bound to
      LPS weakly. In contrast, our studies on antiendotoxin antibodies have revealed
      that antibodies targeted to the hydrophilic oligosaccharides of the endotoxin
      have the potential to bind specifically with high affinity. Development of
      immunotherapeutics that can reduce systemic LPS or other agents, such as
      bactericidal/permeability-increasing protein that can neutralize LPS and limit
      inflammation safely, will enable the role of LPS in chronic heart failure to be
      elucidated and may pave the way to develop a new generation of effective
      therapeutic agents that may be directed to the treatment of chronic heart
      failure.

PMID- 17510603
TI  - Mucosal mast cell proteases are involved in colonic permeability alterations and
      subsequent bacterial translocation in endotoxemic rats.
AB  - LPS-induced endotoxemia is associated with gut immune stimulation, mucosal
      inflammation, colonic paracellular permeability (CPP) alteration, and it promotes
      bacterial translocation (BT). Gut permeability increase linked to LPS promotes
      mucosal barrier dysfunction resulting to BT. However, the mechanisms involved in
      these alterations remain unknown. We aimed to evaluate the role of colonic
      mucosal mast cells and luminal serine protease activity (PA) in the alterations
      of CPP and BT induced by LPS. Rats receiving doxantrazole, a mast cell
      stabilizer, combined or not with LPS from Escherichia coli and CPP as well as BT
      were evaluated after each treatment. Mucosal mast cell activation was assessed by
      histological methods and by rat mast cell protease 2 level measurement in colonic
      content. Colonic luminal PA and mucosal inflammation (myeloperoxidase activity)
      were biochemically determined. In addition, the ability of luminal contents to
      act on CPP was evaluated in vitro in Ussing chambers. Peripheral administration
      of LPS promoted mast cell degranulation and increased CPP, BT, mucosal
      myeloperoxidase activity as well as rat mast cell protease 2 levels, and PA in
      colonic content. LPS-induced CPP increase and BT were prevented by doxantrazole.
      In vitro, exposure of the apical side of colonic tissues with supernatants from
      colonic contents of LPS-treated rats increased CPP. This effect was blocked by
      the serine protease inhibitor soybean trypsin inhibitor. Our data bring evidence
      of a key role of mucosal mast cells in LPS-induced increase of CPP and BT through
      the release of serine proteases into the colonic lumen.

PMID- 17510604
TI  - Dietary ganglioside inhibits acute inflammatory signals in intestinal mucosa and
      blood induced by systemic inflammation of Escherichia coli lipopolysaccharide.
AB  - Our previous study demonstrated that feeding ganglioside increased total
      ganglioside content while decreasing cholesterol and caveolin-1 content in
      developing rat intestinal lipid microdomains. Cholesterol or caveolin depletion
      in membranes inhibits inflammatory signaling by disrupting microdomain structure.
      We hypothesized that dietary ganglioside-induced reduction in cholesterol content
      will reduce proinflammatory mediators in the intestinal mucosa after acute
      exposure to bacterial endotoxin. Weanling rats were fed semipurified diets with
      0.1% (wt/wt of total fat) gangliosides (treatment) or without ganglioside
      (control). After 2 weeks of feeding, half of animals from each diet group were
      injected with saline or lipopolysaccharide (LPS) endotoxin (Escherichia coli
      serotype O111:B4, intraperitoneal, 3 mg/kg body weight) to induce acute gut
      inflammation. Intestinal mucosa and blood were collected after 6 h. The effect of
      dietary ganglioside on proinflammatory mediators including cholesterol, platelet
      activating factor, prostaglandin E2, leukotriene B4 (LTB4), interleukin-1beta (IL
      1beta), and tumor necrosis factor-alpha (TNF-alpha) was determined in inflamed
      mucosa and blood. Feeding animals the control diet increased cholesterol content
      in intestinal lipid microdomains by 92% after LPS injection compared with saline
      injection. Animals fed the ganglioside diet significantly decreased cholesterol
      content in lipid microdomains by 60% compared with animals fed the control diet.
      Feeding animals the ganglioside diet increased total ganglioside content by 90%
      while decreasing platelet-activating factor content by 45% in the inflamed mucosa
      by acute systemic exposure to LPS compared with animals fed the control diet.
      When animals were fed the ganglioside diet, the levels of prostaglandin E2, LTB4,
      IL-1beta, and TNF-alpha were lower in inflamed mucosa, and LTB4, IL-1beta, and
      TNF-alpha were decreased in plasma by 41%, 58%, and 55% compared with control
      animals, respectively. The present study demonstrates that dietary gangliosides
      inhibit proinflammatory signals in the intestine and blood induced by acute
      inflammation of LPS and suggests therapeutic potential in the treatment and
      management of acute local and systemic inflammatory diseases.

PMID- 17510605
TI  - Angiotensin-converting enzyme inhibitor captopril prevents oleic acid-induced
      severe acute lung injury in rats.
AB  - Lack of specific and efficient therapy leads to the high mortality rate of acute
      lung injury (ALI) and acute respiratory distress (ARDS). Recent evidence implies
      that angiotensin-converting enzyme (ACE) plays an important role in the
      pathogenesis of ALI. Pharmaceutical inhibitors of ACE have been used clinically
      for hypertension but not for ALI/ARDS yet. The objective was to study the effects
      of ACE inhibition with captopril on severe lung injury induced by oleic acid (OA)
      in rats. Oleic acid was intravenously injected into Sprague Dawley rats, followed
      by i.p. administration of captopril or saline control. Lung injury, endothelium
      damage and related molecules, and disturbance of coagulation were examined in
      comparison between the treated and the nontreated groups. An OA-induced ALI was
      featured with thickening of the alveolar septa, alveolar hemorrhage, and
      infiltration of inflammatory cells. Comparing with the nontreated OA group, the
      administration of captopril prevented the rats from OA-induced severe lungs
      injury, with a significantly lower lung injury score, less albumin content and
      infiltrated cells in the alveoli, decreased wet/dry weight ratio of the lung
      tissues, and improved lung function (PaO2 per fraction of inspired oxygen).
      Captopril also dramatically reduced the expression of intercellular adhesion
      molecule-1 in the lung tissue and in the circulating endothelial cells in the
      blood, indicating a protective effect on endothelial cells activation/damage.
      Moreover, captopril treatment led to a blockage of nuclear factor kappaB
      activation in lung tissues and to the recovery of the fibrinolytic disturbance.
      Thus, our data suggest that the inhibition of ACE with its clinically used
      inhibitor offers protective effects on ALI/ARDS, implying the potential for
      therapeutic option.

PMID- 17510606
TI  - Hyperlactemia can predict the prognosis of liver resection.
AB  - Although hyperlactemia is known to accompany hepatic failure and metabolic
      acidosis, few reports examined the relationships between lactate concentrations
      and outcome after liver resection. We examined the ability of arterial plasma
      lactate concentration to predict the patient outcome after hepatectomy. The
      relationships of arterial lactate and base excess (BE) measured on admission to
      the intensive care unit (ICU) after hepatectomy to postoperative outcome were
      investigated in 151 consecutive patients. Lactate level was significantly higher
      in nonsurvivors than in survivors (P < 0.001), and in patients with postoperative
      complications than in those without complications (P < 0.001). Base excess was
      significantly reduced in nonsurvivors (P < 0.001) and in patients with
      postoperative complications (P = 0.004). The area under the receiver-operator
      curve of lactate to mortality was 0.86, whereas that of BE to the mortality was
      0.82. Moderate correlation was observed between the lactate level at ICU
      admission and the highest total bilirubin concentration measured within 14 days
      after the surgery (r = 0.61), whereas the correlation between BE and bilirubin
      levels was lower (r = 0.35). Using multivariate analysis, the lactate level
      independently predicted mortality (P = 0.008) and morbidity (P = 0.013). Lactate
      (P < 0.001) and BE (P = 0.0068) levels both independently predicted the highest
      bilirubin concentration. The arterial plasma lactate concentration measured on
      admission to ICU seemed an excellent predictor of patient outcome after liver
      resection.

PMID- 17510607
TI  - THE PPARgamma ligand 15d-PGJ2 modulates macrophage activation after injury in a
      murine trauma model.
AB  - In macrophages, peroxisome proliferator-activated receptor gamma (PPARgamma) has
      been shown to be important for differentiation, and it serves as a negative
      regulator of activation. Major trauma/injury causes a dramatic host response that
      disrupts cellular immune homeostasis and initiates an inflammatory cascade that
      predisposes the injured host to subsequent infections. In prior studies using a
      murine trauma model consisting of femur fracture and hemorrhage, splenic
      macrophages from traumatized mice had significantly enhanced LPS-induced
      cyclooxygenase enzyme (subtype 2) and iNOS production as well as elevated levels
      of inflammatory cytokines at 1 week after injury compared with uninjured
      controls. These up-regulated cellular responses corresponded to increased
      mortality when animals were challenged with LPS or Candida. In the current study,
      we used the injury model to determine the effect of treatment of injured mice
      with the endogenous PPARgamma ligand 15-deoxy-Delta(12-, 14)-PGJ2 (15d-PGJ2). It
      was found that in vivo 15d-PGJ2 treatment significantly reduced the levels of
      inflammatory mediators produced by splenic macrophages 7 days after injury. The
      mechanism of inhibition is dependent on PPARgamma because concomitant treatment
      of animals with the PPARgamma antagonist GW9662 reversed the inhibitory effect of
      15d-PGJ2. Endogenous PPARgamma modulated activation of LPS-induced p38 mitogen
      activated protein kinase. Furthermore, treatment of injured mice with 15d-PGJ2
      conferred a significant survival advantage after infectious challenge induced by
      cecal ligation and puncture. Thus, this PPARgamma ligands significantly attenuate
      the postinjury inflammatory response and improve survival after infectious
      challenge.

PMID- 17510608
TI  - Experience with surgery for entrapment syndrome of the suprascapular nerve.
AB  - BACKGROUND: The suprascapular nerve entrapment syndrome accounts for about 1-2%
      of all causes of shoulder pain and dysfunction. Entrapment may occur at different
      levels and a frequent site of compression is the suprascapular notch, the upper
      border of which is the superior transverse scapular ligament. MATERIAL AND
      METHODS: We studied 5 patients with entrapment of the suprascapular nerve at the
      suprascapular notch, analyzing the pathomechanism of the compression syndrome.
      The outcome of the surgical treatment was evaluated by examining the improvement
      in strength of the supraspinatus and infraspinatus muscles based on the Narakas
      method. The degree of recovery of atrophy of the muscles and pain was also
      evaluated. RESULTS: Following surgical treatment, pain subsided in 4 patients
      (80%), muscle strength improved in three (60%) and in 1 patients (20%) there was
      recovery of muscle mass. CONCLUSIONS: The outcomes of surgery for suprascapular
      entrapment depend on appropriate differential diagnosis, early detection and
      prompt referral for operative treatment whenever such is necessary.

PMID- 17510610
TI  - Prevalence of stroke--United States, 2005.
AB  - Stroke is the third most common cause of death in the United States. Stroke also
      results in substantial health-care expenditures; the mean lifetime cost resulting
      from an ischemic stroke is estimated at $140,000 per patient. Nationwide, costs
      related to stroke are expected to reach an estimated $62.7 billion in 2007.
      Stroke death rates are higher in the southeastern United States, compared with
      other regions of the country; blacks, American Indians/Alaska Natives (AI/ANs),
      Asians/Pacific Islanders, and Hispanics die from stroke at younger ages than
      whites. Regional and national data on self-reported stroke prevalence have been
      published previously; however, state-specific prevalence data for persons with a
      history of stroke have not. To provide national-level stroke prevalence estimates
      by age group, sex, race/ethnicity, and education level and overall prevalence
      estimates for each of the 50 states, the U.S. Virgin Islands (USVI), the District
      of Columbia (DC), and Puerto Rico, CDC analyzed data from the 2005 Behavioral
      Risk Factor Surveillance System (BRFSS) survey. This report summarizes the
      results of that analysis and provides the first state-based prevalence estimates
      of stroke. The results indicated that, in 2005, substantial differences existed
      in the prevalence of stroke by state/territory, race/ethnicity, age group, and
      education level. To lower the incidence of stroke and meet the Healthy People
      2010 objective to reduce stroke deaths (objective no. 12-7) and the overall goal
      to eliminate health disparities, public health programs should augment stroke
      risk-factor prevention and educational measures in disproportionately affected
      regions and populations.

PMID- 17510609
TI  - Complications of dislocated calcaneal fractures.
AB  - BACKGROUND: Calcaneal fractures are the most common of all tarsal fractures, with
      the majority being the result of high energy injuries causing comminution of bone
      and lesions of the posterior articular surface. If the bone fragments are left
      dislocated or non-operative reduction is attempted, the outcome is poor, often
      with chronic disability. On the other hand, operative treatment does not always
      lead to a good result and there is an inherent risk of devastating complications.
      MATERIAL AND METHODS: During a 3-year period (2002-2005) the authors treated
      operatively (by open reduction and internal fixation) 23 dislocated calcaneal
      fractures involving the posterior calcaneotalar joint. A control group of 12
      patients was treated non-operatively or using minimally invasive techniques.
      Medium-term results were compared by evaluating the Bohler and Gissane angles and
      the shape of the posterior calcaneal articular surface on radiographs (lateral
      and Broden views), while functional outcomes were rated according to the
      Creighton-Nebraska scale. Complications not included into this scheme were noted.
      RESULTS: Both anatomic and functional results were markedly better in the group
      treated with open reduction and internal fixation. In this group, there were
      three cases of infectious complications that were attributed to the surgical
      procedure, while in the other group, two such cases were associated with open
      fractures. Both groups developed clawing of the toes. The quality of reduction
      was always unsatisfactory in the non-operative group. CONCLUSIONS: 1.
      Complications of calcaneal fractures significantly worsen the therapeutic
      outcome. 2. Proper care based on meticulous evaluation of the foot in the early
      period is crucial for reducing the incidence of complications.

PMID- 17510611
TI  - Prehospital and hospital delays after stroke onset--United States, 2005-2006.
AB  - Each year approximately 700,000 persons in the United States have a new or
      recurrent stroke; of these persons, 15%-30% become permanently disabled, and 20%
      require institutionalization during the first 3 months after the stroke. The
      severity of stroke-related disability can be reduced if timely and appropriate
      treatment is received. Patients with ischemic stroke may be eligible for
      treatment with intravenous thrombolytic (i.e., tissue plasminogen activator [t
      PA]) therapy within 3 hours of symptom onset. Receipt of this treatment usually
      requires patients to recognize stroke symptoms and receive prompt transport to a
      hospital emergency department (ED), where timely evaluation and brain imaging
      (i.e., computed tomography or magnetic resonance imaging) can take place. For
      patients eligible for t-PA, evidence suggests that the earlier patients are
      treated after the onset of symptoms the greater the likelihood of a more
      favorable outcome. In 2001, Congress established the Paul Coverdell National
      Acute Stroke Registry to measure and track the quality of care provided to acute
      stroke patients. To assess prehospital delays from onset of stroke symptoms to ED
      arrival and hospital delays from ED arrival to receipt of brain imaging, CDC
      analyzed data from the four states participating in the national stroke registry.
      The results of that analysis indicated that fewer than half (48.0%) of stroke
      patients for whom onset data were available arrived at the ED within 2 hours of
      symptom onset, and prehospital delays were shorter for persons transported to the
      ED by ambulance (i.e., emergency medical services) than for persons who did not
      receive ambulance transport. The interval between ED arrival and brain imaging
      also was significantly reduced for those arriving by ambulance. More extensive
      public education is needed regarding early recognition of stroke and the urgency
      of telephoning 9-1-1 to receive ambulance transport. Shortening prehospital and
      hospital delays will increase the proportion of ischemic stroke patients who are
      eligible to receive t-PA therapy and reduce their risk for severe disability from
      stroke.

PMID- 17510612
TI  - Household transmission of vaccinia virus from contact with a military smallpox
      vaccinee--Illinois and Indiana, 2007.
AB  - On March 7, 2007, the Chicago Department of Public Health and the University of
      Chicago Pediatric Infectious Disease Service and Infection Control Program
      notified CDC of a child with presumed eczema vaccinatum (EV), a life-threatening
      complication of vaccinia virus infection. This is the first reported EV case in
      the United States since 1988. This report summarizes the epidemiologic and
      environmental investigations conducted by local, state, and federal public health
      authorities in Illinois and Indiana to determine the source of exposure and to
      identify and monitor other persons at risk for vaccinia virus infection. This
      case highlights the need for clinicians to maintain a high index of suspicion
      when evaluating recently vaccinated patients and their family members with
      vesiculopustular rash.

PMID- 17510613
TI  - Fatal injuries among children by race and ethnicity--United States, 1999-2002.
AB  - PROBLEM/CONDITION: In the United States, unintentional injury, homicide, and
      suicide are the first, second, and fourth leading causes of death among persons
      aged 1-19 years, respectively; the highest rates have occurred among minority
      populations. The effects of age on the difference in rates between white and
      minority children and the mechanisms of injury that contribute most to that
      difference have not been previously reported. REPORTING PERIOD COVERED: Data are
      presented for fatal injuries among children in the United States by
      race/ethnicity and mechanism of injury during 1999-2002. Trends in injury
      mortality by race/ethnicity are provided for 1982-2002. DESCRIPTION OF SYSTEM:
      Fatal injury data were derived from death certificates reported through CDC's
      National Vital Statistics System. RESULTS: During 1999-2002, among infants aged
      <1 year, American Indian/Alaska Natives (AI/ANs) and blacks had consistently
      higher total injury death rates than other racial/ethnic populations. Both
      populations had more than twice the rate of injury death compared with white
      infants. Black infants had the highest rates of unintentional suffocation and
      homicide, whereas AI/AN infants had the highest rate of motor-vehicle (MV)
      traffic death. Among children aged 1-9 years, AI/ANs and blacks had the highest
      injury death rates. AI/ANs aged 1-9 years had the highest rates of MV-traffic
      death and drowning; in contrast, blacks aged 1-9 years had the highest rates of
      homicide and fire/burn death. Among children aged 10-19 years, AI/ANs and blacks
      consistently had higher total injury death rates than whites. AI/ANs aged 10-19
      years had the highest rates of suicide and MV-traffic death, and blacks aged 10
      19 years had the highest rates of homicide. The disparity in injury mortality
      rates by race/ethnicity during 1982-1985 had not declined by 1999-2002.
      INTERPRETATION: Significant disparities in injury rates still exist between white
      and minority children. Disparities varied by age and mechanism of injury.
      Hispanics and Asian/Pacific Islanders consistently had lower risk, whereas AI/ANs
      and blacks consistently had higher risk for fatal injuries than other
      racial/ethnic populations. PUBLIC HEALTH ACTIONS: Educational, regulatory, and
      environmental modification strategies (e.g., home visitation programs, safety
      belt laws, and swimming pool fencing) have been developed for each type of injury
      for use by health-care providers and government agencies.

PMID- 17510614
TI  - Trauma in context.

PMID- 17510615
TI  - The analytic encounter, a scene of clashing cultures.
AB  - Three wars (WWII, the Vietnam War and the Iraq War) as well as the experience of
      immigration impacted on the analytic situation as described in this paper. A
      first generation immigrant patient, who was also a Vietnam veteran, and the
      immigrant analyst came together in harmony and in discord, around the issues of
      their common experiences of war and being an immigrant. The onset of the Iraq war
      brought these issues into a sharp focus in the mid-phase of an on-going analysis.
      The paper explores how countertransferential experiences of war and immigration
      were used to further analytic work. It is often assumed that analogous external
      experiences can give rise to greater empathic understanding on the part of the
      analyst. In this paper,I hope to demonstrate that there are both advantages and
      serious pitfalls in experiential overlaps between the cultural experiences of the
      analyst and patient.

PMID- 17510616
TI  - Enactments and dissociations driven by cultural differences.
AB  - Cultural differences between the analytic dyad can foster powerful transference
      counter-transference feelings and potentially promote traumatic re-enactments.
      Those patients who are more directly affected by traumatic experiences may be
      able to verbalize what has happened to them only if they are convinced that their
      analysts are "taking in their horror, holding it for them, responding to it
      emotionally (reenacting) and giving it back in more modulated and containable"
      manner (Davies, 1997, p. 24). These mutual enactments that emerge in patients and
      their analysts can be understood as dissociated self-states. Clinical material is
      presented from the treatment of an African-American inner-city teenager and an
      Israeli teenage soldier to illustrate the emergence of enactments and
      dissociation in patient-analyst dyads.

PMID- 17510617
TI  - Found in translation: discussion of Galdi and Cohen.
AB  - Papers by Galdi and Cohen are appreciated and discussed. Trauma is seen as
      occurring in a culturally based matrix of meanings. Galdi and Cohen's case
      material is discussed in terms of the cultural symmetry and contrast between
      patient and therapist. The assault of trauma on meaning through mechanisms of
      dissociation, alienation and psychic numbing is explored. Therapy is examined as
      the restoration of meaning through the creation of a relationship through the
      shared language of empathy.

PMID- 17510618
TI  - Society's use of the hero following a national trauma.
AB  - The terrorist nature of the attacks on September 11th, the number of deaths on
      American soil and the direct involvement of society as virtual eyewitnesses of
      the events of that day had a traumatizing impact on the cultural consciousness.
      The interpersonal, socio-cultural manifestations of traumatic grief are explored
      through an analysis of the creation and transformation of its national heroes,
      the New York City firefighters, in the public mind over time. Mechanisms of
      identification, dissociation and splitting were manifested through the erection
      of physical and social boundaries around 9/11, which allowed for idealization at
      a safe distance followed by de-cathexis when the collective sought to abort the
      mourning process and overcome the pain and helplessness of traumatic grief by
      going to war.

PMID- 17510619
TI  - The question of survival: the death of desire and the weight of life.
AB  - This article aims to document the psychic injuries of torture. Psychic deadness,
      erasure of intersubjectivity, refusal of meaning-making, perversion of agency,
      and an inability to bear desire constitute the core features of the post
      traumatic landscape of torture. The existential challenges in traumatized lives
      is examined, and questions are also raised about the ethics and unconscious
      defensive functions of the term "survival." Clinical materials with various
      torture patients are reported to explore the process of working through the
      losses and paradoxes of trauma. The role of unmourned loss and the defense of
      fetishizing the trauma are highlighted as the motivating force and the problem in
      the current preoccupation with trauma in modern Western culture.

PMID- 17510620
TI  - Nonmentalizing states in early-childhood survivors of the Holocaust:
      developmental considerations regarding treatment of child survivors of genocidal
      atrocities.
AB  - This paper attempts to coalesce considerations of attachment processes, trauma,
      mentalization, and nonverbal behavior to underscore some of the developmental and
      therapeutic challenges demonstrated by older-adult child survivors of the
      Holocaust, and by implication, other child victims of similar genocidal and
      traumatic events. Young child survivors experienced not only their own traumatic
      exposure to violence, harm, and loss, but also the stress-transmission of the
      adult caregivers who raised them in the years that followed. For some, the
      horrendous losses, combined with impediments to organizing relationships, and to
      experiences of predictable and trusted continuities, negatively impact the
      development of the reflective function, and of interpretive skills basic to
      successful implicit relatedness and explicit exchanges. "Neutral flow" of bodily
      tension and shape often signals the freezing accompanying nonmentalizing states.
      Misalignments in individual personality structure and discordances in
      interpersonal exchange underscore the need to address fundamental building blocks
      of relatedness and mentalization in the therapeutic process.

PMID- 17510621
TI  - Contaminated generativity: Holocaust survivors and their children in Germany.
AB  - This paper addresses the trauma transfer from survivors of the Shoah to the
      Second Generation in Germany. What does it mean for both generations to beget
      children after Auschwitz? This necessarily entails perceiving non-Jewish Germans
      and their way of dealing with history. Survivors cannot live without their
      memory, nor is it possible for them to conceive of a life unencumbered by this
      constant "contaminant". It is not possible to integrate the persecution
      experiences. On the contrary, decades after liberation, dissociated elements of
      traumatic memories penetrate everyday experiences, thought, affect and
      imagination as contaminants. Occasionally, these fragments of persecution
      experiences, like "encapsulated memories" hidden in crypts suddenly break open
      and frighten the survivors themselves and even more so the people around them.

PMID- 17510622
TI  - Hope in a time of cholera.
AB  - What are the internal conditions or mental states that may facilitate the moving
      on with life? How does one explain that some, after undergoing severe trauma,
      fail to go on with productive and creative lives while others do? In this paper,
      I shall explore the effect of hope and its central position in mobilizing
      traumatized individuals so that they can move on with their lives. I shall be
      focusing on a specific aspect of trauma often neglected in the literature, namely
      the trauma elicited by the sudden, almost overnight loss of monetary funds
      accumulated over years of hard work. I will be referring to the psychological
      impact suffered by Argentineans after severe economic measures taken by the
      government in late 2001. I shall delve into these solutions and attempt to
      explore their influence on a contemporary exodus from Argentina. Hope nurtured by
      despair will be discussed. Is hope a mere palliative, a mental configuration
      coupling with a furtive affective state? Hope joins the ranks of religion in
      building a buffer against the silent awareness of inner despair-the most private
      of madness. I shall try to discuss how hope brings to the fore psyche's devices
      that are deployed in attempting to deal with our deepest fears.

PMID- 17510623
TI  - Scientific meeting of the American Institute for Psychoanalysis.

PMID- 17510628
TI  - YscU recognizes translocators as export substrates of the Yersinia injectisome.
AB  - YscU is an essential component of the export apparatus of the Yersinia
      injectisome. It consists of an N-terminal transmembrane domain and a long
      cytoplasmic C-terminal domain, which undergoes auto-cleavage at a NPTH site.
      Substitutions N263A and P264A prevented cleavage of YscU and abolished export of
      LcrV, YopB and YopD but not of Yop effectors. As a consequence, yscU(N263A)
      mutant bacteria made needles without the LcrV tip complex and they could not form
      translocation pores. The graft of the export signal of the effector YopE, at the
      N-terminus of LcrV, restored LcrV export and assembly of the tip complex. Thus,
      YscU cleavage is required to acquire the conformation allowing recognition of
      translocators, which represent an individual category of substrates in the
      hierarchy of export. In addition, yscU(N263A) mutant bacteria exported reduced
      amounts of the YscP ruler and made longer needles. Increasing YscP export
      resulted in needles with normal size, depending on the length of the ruler.
      Hence, the effect of the yscU(N263A) mutation on needle length was the
      consequence of a reduced YscP export.

PMID- 17510629
TI  - A genome-wide role for CHD remodelling factors and Nap1 in nucleosome
      disassembly.
AB  - Chromatin remodelling factors and histone chaperones were previously shown to
      cooperatively affect nucleosome assembly and disassembly processes in vitro.
      Here, we show that Schizosaccharomyces pombe CHD remodellers, the Hrp1 and Hrp3
      paralogs physically interact with the histone chaperone Nap1. Genome-wide
      analysis of Hrp1, Hrp3 and Nap1 occupancy, combined with nucleosome density
      measurements revealed that the CHD factors and Nap1 colocalized in particular to
      promoter regions where they remove nucleosomes near the transcriptional start
      site. Hrp1 and Hrp3 also regulate nucleosome density in coding regions, where
      they have redundant roles to stimulate transcription. Previously, DNA replication
      dependent and -independent nucleosome disassembly processes have been described.
      We found that nucleosome density increased in the hrp1 mutant in the absence of
      DNA replication. Finally, regions where nucleosome density increased in hrp1,
      hrp3 and nap1 mutants also showed nucleosome density and histone modification
      changes in HDAC and HAT mutants. Thus, this study revealed an important in vivo
      role for CHD remodellers and Nap1 in nucleosome disassembly at promoters and
      coding regions, which are linked to changes in histone acetylation.

PMID- 17510630
TI  - Prion protein with an octapeptide insertion has impaired neuroprotective activity
      in transgenic mice.
AB  - Familial prion diseases are due to dominantly inherited, germline mutations in
      the PRNP gene that encodes the prion protein (PrP). The cellular mechanism
      underlying the pathogenic effect of these mutations remains uncertain. To
      investigate whether pathogenic mutations impair a normal, physiological activity
      of PrP, we have crossed Tg(PG14) mice, which express PrP with an octapeptide
      insertion associated with an inherited prion dementia, with Tg(PrPDelta32-134)
      mice. Tg(PrPDelta32-134) mice, which express an N-terminally truncated form of
      PrP, spontaneously develop a neurodegenerative phenotype that is
      stoichiometrically reversed by coexpression of wild-type PrP. We find that, at
      equivalent expression levels, PG14 PrP is significantly less efficient than wild
      type PrP in suppressing the development of clinical symptoms and neuropathology
      in Tg(PrPDelta32-134) mice. Thus, our results suggest that some features of the
      neurological illness associated with inherited PrP mutations may be attributable
      to a loss of PrP neuroprotective function. This mechanism stands in contrast to
      the toxic gain-of-function mechanisms that are usually invoked to explain the
      pathogenesis of dominantly inherited neurodegenerative disorders.

PMID- 17510631
TI  - Neuronal apoptosis and reversible motor deficit in dominant-negative GSK-3
      conditional transgenic mice.
AB  - Increased glycogen synthase kinase-3 (GSK-3) activity is believed to contribute
      to the etiology of chronic disorders like Alzheimer's disease and diabetes, thus
      supporting therapeutic potential of GSK-3 inhibitors. However, sustained GSK-3
      inhibition might induce tumorigenesis through beta-catenin-APC dysregulation.
      Besides, sustained in vivo inhibition by genetic means (constitutive knock-out
      mice) revealed unexpected embryonic lethality due to massive hepatocyte
      apoptosis. Here, we have generated transgenic mice with conditional (tetracycline
      system) expression of dominant-negative-GSK-3 as an alternative genetic approach
      to predict the outcome of chronic GSK-3 inhibition, either per se, or in
      combination with mouse models of disease. By choosing a postnatal neuron-specific
      promoter, here we specifically address the neurological consequences. Tet/DN-GSK
      3 mice showed increased neuronal apoptosis and impaired motor coordination.
      Interestingly, DN-GSK-3 expression shut-down restored normal GSK-3 activity and
      re-established normal incidence of apoptosis and motor coordination. These
      results reveal the importance of intact GSK-3 activity for adult neuron viability
      and physiology and warn of potential neurological toxicity of GSK-3
      pharmacological inhibition beyond physiological levels. Interestingly, the
      reversibility data also suggest that unwanted side effects are likely to revert
      if excessive GSK-3 inhibition is halted.

PMID- 17510632
TI  - How myosin VI coordinates its heads during processive movement.
AB  - A processive molecular motor must coordinate the enzymatic state of its two
      catalytic domains in order to prevent premature detachment from its track. For
      myosin V, internal strain produced when both heads of are attached to an actin
      track prevents completion of the lever arm swing of the lead head and blocks ADP
      release. However, this mechanism cannot work for myosin VI, since its lever arm
      positions are reversed. Here, we demonstrate that myosin VI gating is achieved
      instead by blocking ATP binding to the lead head once it has released its ADP.
      The structural basis for this unique gating mechanism involves an insert near the
      nucleotide binding pocket that is found only in class VI myosin. Reverse strain
      greatly favors binding of ADP to the lead head, which makes it possible for
      myosin VI to function as a processive transporter as well as an actin-based
      anchor. While this mechanism is unlike that of any other myosin superfamily
      member, it bears remarkable similarities to that of another processive motor from
      a different superfamily--kinesin I.

PMID- 17510633
TI  - Distinct IFT mechanisms contribute to the generation of ciliary structural
      diversity in C. elegans.
AB  - Individual cell types can elaborate morphologically diverse cilia. Cilia are
      assembled via intraflagellar transport (IFT) of ciliary precursors; however, the
      mechanisms that generate ciliary diversity are unknown. Here, we examine IFT in
      the structurally distinct cilia of the ASH/ASI and the AWB chemosensory neurons
      in Caenorhabditis elegans, enabling us to compare IFT in specific cilia types. We
      show that unlike in the ASH/ASI cilia, the OSM-3 kinesin moves independently of
      the kinesin-II motor in the AWB cilia. Although OSM-3 is essential to extend the
      distal segments of the ASH/ASI cilia, it is not required to build the AWB distal
      segments. Mutations in the fkh-2 forkhead domain gene result in AWB-specific
      defects in ciliary morphology, and FKH-2 regulates kinesin-II subunit gene
      expression specifically in AWB. Our results suggest that cell-specific regulation
      of IFT contributes to the generation of ciliary diversity, and provide insights
      into the networks coupling the acquisition of ciliary specializations with other
      aspects of cell fate.

PMID- 17510638
TI  - The role of immunosuppression in gene- and cell-based treatments for duchenne
      muscular dystrophy.

PMID- 17510634
TI  - Staufen1 regulates diverse classes of mammalian transcripts.
AB  - It is currently unknown how extensively the double-stranded RNA-binding protein
      Staufen (Stau)1 is utilized by mammalian cells to regulate gene expression. To
      date, Stau1 binding to the 3'-untranslated region (3'-UTR) of ADP ribosylation
      factor (ARF)1 mRNA has been shown to target ARF1 mRNA for Stau1-mediated mRNA
      decay (SMD). ARF1 SMD depends on translation and recruitment of the nonsense
      mediated mRNA decay factor Upf1 to the ARF1 3'-UTR by Stau1. Here, we demonstrate
      that Stau1 binds to a complex structure within the ARF1 3'-UTR. We also use
      microarrays to show that 1.1 and 1.0% of the 11 569 HeLa-cell transcripts that
      were analyzed are upregulated and downregulated, respectively, at least two-fold
      upon Stau1 depletion in three independently performed experiments. We localize
      the Stau1 binding site to the 3'-UTR of four mRNAs that we define as natural SMD
      targets. Additionally, we provide evidence that the efficiency of SMD increases
      during the differentiation of C2C12 myoblasts to myotubes. We propose that Stau1
      influences the expression of a wide variety of physiologic transcripts and
      metabolic pathways.

PMID- 17510641
TI  - A new look for chemical information.

PMID- 17510642
TI  - Diversity in chemistry: catalyzing change.

PMID- 17510643
TI  - A QUICk look at O-GlcNAc dynamics.

PMID- 17510644
TI  - Stimulating the cell's appetite for itself.

PMID- 17510645
TI  - Smells like bread.

PMID- 17510646
TI  - A sugar-coated switch for cellular growth and arrest.

PMID- 17510647
TI  - Sugars synthesized in a snap.

PMID- 17510649
TI  - N-glycan structure dictates extension of protein folding or onset of disposal.
AB  - The endoplasmic reticulum (ER) is the site of folding for proteins that are
      resident in the ER or that are destined for the Golgi, endosomes, lysosomes, the
      plasma membrane, or secretion. Cotranslational addition of preassembled
      glucose(3)-mannose(9)-N-acetylglucosamine(2) core oligosaccharides (N
      glycosylation) is a common event for polypeptides synthesized in this
      compartment. Protein-bound oligosaccharides are exposed to several ER glycanases
      that sequentially remove terminal glucose or mannose residues. Their activity
      must be tightly regulated because the N-glycan composition determines whether the
      associated protein is subjected to folding attempts in the ER lumen or whether it
      is retrotranslocated into the cytosol and degraded.

PMID- 17510651
TI  - Crystalline retinopathy associated with chronic macular hole; a report of two
      cases.

PMID- 17510652
TI  - Anterior chemodenervation of levator palpebrae superioris with botulinum toxin
      type-A (Botox) to induce temporary ptosis for corneal protection.
AB  - AIM: To evaluate the effectiveness of anterior chemodenervation of levator
      palpebrae superioris with Botulinum toxin type A (Botox) to induce temporary
      ptosis for corneal protection, and assess the incidence of superior rectus
      underaction. METHODS: Prospective interventional case series. Patients with
      ocular surface pathology requiring temporary tarsorrhaphy underwent
      transcutaneous anterior chemodenervation of levator palpebrae superioris with
      Botox. The onset and duration of ptosis, corneal healing, and superior rectus
      underaction was evaluated. RESULTS: Ten eyes of 10 patients underwent
      transcutaneous anterior chemodenervation of levator muscle. Five patients had
      Bells palsy with exposure keratopathy, four patients had persistent epithelial
      defect, and one had neurotrophic ulcer. The median age at presentation was 30
      years. Median dose of Botulinum toxin injection was 12.5 U (range 10-15 U). The
      mean palpebral fissure height of 9 mm (SD+/-2.1 mm) before injection, reduced to
      2.8 mm (SD+/-1.9 mm) at 1-week post-injection. More than 50% reduction in
      palpebral fissure height was seen in nine out of 10 eyes (90%, 95% CI 71.4-100%)
      at 1 week, seven of nine eyes (77.8%, 95% CI 50.6-100%) at 2 weeks, and two of
      nine eyes (22.2%, 95% CI 0-49.4%) at 4 weeks, and returned to pretreatment level
      after mean duration of 9.2 weeks (range 5-16 weeks). Superior rectus underaction
      was not noted in any of the patient (95% CI 0-30%). Corneal pathology improved in
      all cases. CONCLUSION: Anterior chemodenervation of levator palpebrae superioris
      with Botulinum toxin type A (Botox) induces significant temporary ptosis and aids
      in corneal healing. Anterior placement of the toxin injection may avoid superior
      rectus underaction.

PMID- 17510653
TI  - Variables affecting refractive outcome following LASIK for myopia.
AB  - AIM: To investigate factors affecting refractive outcome following LASIK for
      myopia. METHOD: Six hundred and seventy-four consecutive uncomplicated myopic
      LASIK surgeries, performed by a single surgeon, either using the Technolas 217
      planoscan (n=372) or the NIDEK EC 5000 (n=302), were evaluated. Stratified random
      sampling was used to match the groups for refractive error, patient age, and
      gender. The final analysis included 302 patients from each treatment group.
      Conditions were identical for both surgeries, and pre-operative refractive errors
      were between -1.00 and -14.00 DS and <-1.50 DC. Refractive success was defined as
      -0.50 to +0.50 DS of the targeted refraction measured 3 months after surgery. A
      stepwise logistical regression analysis was used to determine variables
      associated with refractive failure. RESULTS: A successful refractive outcome was
      achieved in 78% (235/302) of surgeries using the Technolas laser and in 88%
      (266/302) using the NIDEK laser. Predictor variables for not achieving refractive
      success were pre-operative refractive error of above -5.00 DS, age more than 40
      years, and surgery performed with the Technolas laser. CONCLUSION: Both the
      Technolas 217 and the NIDEK EC-5000 excimer lasers achieve a successful
      refractive outcome in the majority of cases. However, patient and surgical
      factors can influence refractive outcome.

PMID- 17510654
TI  - Of wombats and whales: telomere tales in Madrid. Conference on telomeres and
      telomerase.

PMID- 17510655
TI  - Conserved roles of Sam50 and metaxins in VDAC biogenesis.
AB  - Voltage-dependent anion-selective channel (VDAC) is a beta-barrel protein in the
      outer mitochondrial membrane that is necessary for metabolite exchange with the
      cytosol and is proposed to be involved in certain forms of apoptosis. We studied
      the biogenesis of VDAC in human mitochondria by depleting the components of the
      mitochondrial import machinery by using RNA interference. Here, we show the
      importance of the translocase of the outer mitochondrial membrane (TOM) complex
      in the import of the VDAC precursor. The deletion of Sam50, the central component
      of the sorting and assembly machinery (SAM), led to both a strong defect in the
      assembly of VDAC and a reduction in the steady-state level of VDAC. Metaxin 2
      depleted mitochondria had reduced levels of metaxin 1 and were deficient in
      import and assembly of VDAC and Tom40, but not of three matrix-targeted
      precursors. We also observed a reduction in the levels of metaxin 1 and metaxin 2
      in Sam50-depleted mitochondria, implying a connection between these three
      proteins, although Sam50 and metaxins seemed to be in different complexes. We
      conclude that the pathway of VDAC biogenesis in human mitochondria involves the
      TOM complex, Sam50 and metaxins, and that it is evolutionarily conserved.

PMID- 17510656
TI  - Necessary and sufficient factors for the import of transfer RNA into the
      kinetoplast mitochondrion.
AB  - The mechanism of active transport of transfer RNA (tRNA) across membranes is
      largely unknown. Factors mediating the import of tRNA into the kinetoplast
      mitochondrion of the protozoon Leishmania tropica are organized into a
      multiprotein RNA import complex (RIC) at the inner membrane. Here, we present the
      complete characterization of the identities and functions of the subunits of this
      complex. The complex contains three mitochondrion- and eight nuclear-encoded
      subunits; six of the latter are necessary and sufficient for import. Antisense
      mediated knockdown of essential subunits resulted in the depletion of
      mitochondrial tRNAs and inhibition of organellar translation. Functional
      complexes were reconstituted with recombinant subunits expressed in Escherichia
      coli. Several essential RIC subunits are identical to specific subunits of
      respiratory complexes. These findings provide new information on the evolution of
      tRNA import and the foundation for detailed structural and mechanistic studies.

PMID- 17510657
TI  - 14th Euroconference on Apoptosis: 'death or survival? Fate in Sardinia'.

PMID- 17510658
TI  - Apoptosis-based dual molecular targeting by INNO-406, a second-generation Bcr-Abl
      inhibitor, and ABT-737, an inhibitor of antiapoptotic Bcl-2 proteins, against Bcr
      Abl-positive leukemia.
AB  - Bcr-Abl is the cause of Philadelphia-positive (Ph(+)) leukemias and also
      constitutes their principal therapeutic target, as exemplified by dramatic
      effects of imatinib mesylate. However, mono-targeting of Bcr-Abl does not always
      achieve complete leukemia eradication, and additional strategies those enable
      complete elimination of leukemic cells are desired to develop. Here we
      demonstrate that INNO-406, a much more active Bcr-Abl tyrosine kinase inhibitor
      than imatinib, augments the activities of several proapoptotic Bcl-2 homology
      (BH)3-only proteins (Bim, Bad, Bmf and Bik) and induces apoptosis in Ph(+)
      leukemia cells via Bcl-2 family-regulated intrinsic apoptosis pathway. ABT-737,
      an inhibitor of antiapoptotic Bcl-2 and Bcl-X(L), greatly enhanced the apoptosis
      by INNO-406, even in INNO-406-less sensitive cells with Bcr-Abl point mutations
      except T315I mutation. In contrast, co-treatment with INNO-406 and other
      pharmacologic inducers of those BH3-only proteins, such as 17
      allylaminogeldanamycin, an heat shock protein-90 inhibitor, or PS-341, a
      proteasome inhibitor, did not further increase the BH3-only protein levels or
      sensitize leukemic cells to INNO-406-induced apoptosis, suggesting a limit to how
      much expression levels of BH3-only proteins can be increased by anticancer
      agents. Thus, double-barrelled molecular targeting for Bcr-Abl-driven oncogenic
      signaling and the cell protection by antiapoptotic Bcl-2 family proteins may be
      the rational therapeutic approach for eradicating Ph(+) leukemic cells.

PMID- 17510659
TI  - The proapoptotic BCL-2 family member BIM mediates motoneuron loss in a model of
      amyotrophic lateral sclerosis.

PMID- 17510660
TI  - Bcl-2 induces pro-oxidant state by engaging mitochondrial respiration in tumor
      cells.
AB  - Mitochondrial respiration, the key process behind cellular energy production, is
      critical for cell proliferation, growth and survival. However, the regulation of
      mitochondrial respiratory function in tumor cells is not well understood. In this
      study, we propose a model whereby tumor cells possess the capacity to fine-tune
      the balance between energy demands and mitochondrial reactive oxygen species
      (ROS) status, to maintain a milieu optimal for survival. This is achieved through
      the moderation of mitochondrial respiration, depending on the ROS context within
      the organelle, with the main players being Bcl-2 and cytochrome c oxidase (COX).
      We report a higher level of COX activity, oxygen consumption and mitochondrial
      respiration in tumor cells overexpressing Bcl-2. Transient overexpression, gene
      silencing and pharmacological inhibition of Bcl-2 corroborate these findings.
      Interestingly, Bcl-2 is also able to regulate mitochondrial respiration and COX
      activity in the face of mounting ROS levels, triggered by mitochondrial complex
      inhibitors. In this respect, it is plausible to suggest that Bcl-2 may be able to
      create an environment, most suited for survival by adjusting mitochondrial
      respiration accordingly to meet energy requirements, without incurring an
      overwhelming, detrimental increase in intracellular ROS.

PMID- 17510661
TI  - The post-genomic era: workshop on chromatin immunoprecipitation-related
      techniques.

PMID- 17510662
TI  - Homeless in North and West Belfast: an oral health needs assessment.
AB  - AIM: The aim was to assess the oral health needs of a homeless population
      residing in North and West Belfast Health and Social Services Trust area, in
      order to determine levels of unmet need and allow recommendations for service
      delivery to be made. METHOD: A sample of single homeless people was gathered
      using a snowballing sampling technique. Fourteen hostels located in North and
      West Belfast were visited in tandem with the homeless health care coordinator.
      All consenting participants were asked to complete a detailed medical history
      questionnaire and a questionnaire to assess their health and psycho-social needs,
      dental anxiety and oral health related quality of life. All participants received
      an oral examination. RESULTS: Three hundred and seventeen homeless people
      consented to take part. Two hundred and sixty-seven (84%) were male. Thirty three
      percent of participants had mental health problems including psychotic illness,
      depression and anxiety. Forty-three percent of the sample stated they were
      addicted to alcohol and 3% were registered injecting drug users. Five percent
      (16) of the sample had soft tissue swellings of which two were found to be oral
      cancer. The participants had a mean D(3cv)MFT of 16.16 (95% CI: 15.71, 17.46).
      Seventy-fi ve percent of the sample had bleeding gums and calculus; however only
      4%had pocket depths of 6 mm or more. Dental anxiety status was related to dental
      disease experience which impacted negatively on quality of life. Forty-seven
      percent of the participants felt at least occasionally self-conscious and/or felt
      ashamed by the appearance of their teeth. CONCLUSIONS: Health and psychosocial
      factors associated with being homeless must be incorporated into the delivery of
      context-sensitive oral healthcare for this socially excluded population.

PMID- 17510663
TI  - Attitudes of general dental practitioners in the UK to the use of composite
      materials in posterior teeth.
AB  - OBJECTIVE: To determine the opinions and current methods used in placing
      posterior composite restorations by general dental practitioners. SETTING: The
      study was completed by general dental practitioners randomly selected from across
      the UK. METHOD: A questionnaire was devised to gain this information. It was sent
      to 500 UK dentists chosen at random from the general dental register, with an
      explanatory letter and reply-paid envelope. RESULTS: Two hundred and sixty-seven
      replies were received. Sixty-one percent of dentists felt amalgam use had
      decreased over the last five years, 75% felt posterior composite use had
      increased. Regarding choice of posterior material, almost all cited clinical
      indication as the most influential factor while patient's aesthetic demands
      (89%),wish for a certain material (78%) and the dentist's confidence using a
      certain restorative material (76%) were contributing factors. Regarding the
      techniques used, contemporary techniques were employed although there was
      confusion regarding the need for rubber dam and the most appropriate method of
      lining the cavity. A case scenario of a pregnant patient who required treatment
      found that 66% of respondents would place a restoration other than a temporary
      dressing, with 16% placing an amalgam restoration. CONCLUSIONS: The majority of
      dentists surveyed place load bearing posterior composite restorations regularly.
      Their choice of restorative material is influenced by clinical indications and
      the patient's aesthetic demands. The techniques used were appropriate, although
      there was confusion around the need for rubber dam and the most appropriate
      method to line the cavity. There was also confusion in relation to the most
      appropriate materials for use in pregnancy.

PMID- 17510664
TI  - Exploring genetic interactions and networks with yeast.
AB  - The development and application of genetic tools and resources has enabled a
      partial genetic-interaction network for the yeast Saccharomyces cerevisiae to be
      compiled. Analysis of the network, which is ongoing, has already provided a clear
      picture of the nature and scale of the genetic interactions that robustly sustain
      biological systems, and how cellular buffering is achieved at the molecular
      level. Recent studies in yeast have begun to define general principles of genetic
      networks, and also pave the way for similar studies in metazoan model systems. A
      comparative understanding of genetic-interaction networks promises insights into
      some long-standing genetic problems, such as the nature of quantitative traits
      and the basis of complex inherited disease.

PMID- 17510665
TI  - Network motifs: theory and experimental approaches.
AB  - Transcription regulation networks control the expression of genes. The
      transcription networks of well-studied microorganisms appear to be made up of a
      small set of recurring regulation patterns, called network motifs. The same
      network motifs have recently been found in diverse organisms from bacteria to
      humans, suggesting that they serve as basic building blocks of transcription
      networks. Here I review network motifs and their functions, with an emphasis on
      experimental studies. Network motifs in other biological networks are also
      mentioned, including signalling and neuronal networks.

PMID- 17510666
TI  - Spindle orientation, asymmetric division and tumour suppression in Drosophila
      stem cells.
AB  - Recent genetic studies in flies have added further support to an increasing body
      of evidence that suggests that stem cells might be the cell-of-origin of certain
      tumours. Malfunction of the mechanisms that control the division of stem cells
      and the developmental fate of the two resulting daughters could be one of the
      initial events that steers cells into malignant transformation. These studies
      suggest a role for controlled spindle orientation in suppressing stem-cell
      overgrowth. In parallel, the machinery that drives asymmetry in stem cells has
      been further characterized, identifying new components and uncovering the unique,
      highly sophisticated behaviour of centrosomes in these cells.

PMID- 17510667
TI  - Can we develop ethically universal embryonic stem-cell lines?
AB  - Human embryonic stem-cell (hESC) research faces opposition from those who object
      to the destruction of human embryos. Over the past few years, a series of new
      approaches have been proposed for deriving hESC lines without injuring a living
      embryo. Each of these presents scientific challenges and raises ethical and
      political questions. Do any of these methods have the potential to provide a
      source of hESCs that will be acceptable to those who oppose the current
      approaches?

PMID- 17510669
TI  - Genotype-specific weight loss treatment advice: how close are we?
AB  - Obesity, whose prevalence is continually rising, is one of the world's greatest
      health care burdens. This multifactorial condition is associated with many
      obesity-related conditions, such as type 2 diabetes, dyslipidemia, and
      cardiovascular disease. Weight loss is a significant challenge facing those
      wishing to reduce their disease risk. Of course, like obesity itself, weight loss
      is a complex phenomenon dependent on many environmental and genetic influences,
      and thus individual responses to weight loss interventions are incredibly
      variable. Currently, there are 3 major interventions used to reduce weight: diet,
      exercise, and pharmacotherapy. The findings from studies examining gene-diet
      (nutrigenetic), gene-exercise (actigenetic), and gene-pharmaceutical
      (pharmacogenetic) interactions, although not clinically applicable at this time,
      are gaining awareness. This review article summarizes the current evidence to
      support the contribution of DNA sequence variation in genes related to energy
      balance (expenditure and intake) in the response to weight loss intervention.
      There is no doubt that replication using more rigorous study designs that include
      the study of interactions between multiple genes and interventions is required to
      move towards the development of genotype-specific weight loss treatment
      strategies.

PMID- 17510668
TI  - Lipid mediators in membrane rafts are important determinants of human health and
      disease.
AB  - The new field of membrane rafts has provided fresh insight and a novel framework
      in which to understand the interaction, relation, and organization of lipids and
      proteins within cell membranes. This review will examine our current
      understanding of membrane rafts and their role in human health. In addition, the
      effect of various lipids, including dietary lipids, on membrane raft structure
      and function will be discussed. Membrane rafts are found in all cells and are
      characterized by their high concentration of cholesterol, sphingolipids, and
      saturated fatty acids. These lipids impart lateral segregation of membrane
      proteins, thus facilitating the spatial organization and regulation of membrane
      proteins involved in many cellular processes, such as cell proliferation,
      apoptosis, and cell signaling. Therefore, membrane rafts are shedding new light
      on the origins of metabolic disturbances and diseases such as cancer, insulin
      resistance, inflammation, cardiovascular disease, and Alzheimer's disease, which
      will be further discussed in this review.

PMID- 17510670
TI  - Cycling peak power in obese and lean 6- to 8-year-old girls and boys.
AB  - The purpose of this study was to investigate the possible effect of the
      difference in percentage body fat (%BF) and fat-free mass (FFM) on cycling peak
      power (CPP) in 6- to 8-year-old obese and lean untrained girls and boys. Obese
      (35 girls, 35 boys) and lean (35 girls, 35 boys) children were measured for
      obesity, %BF, calculated from skinfold measurements. FFM was calculated as body
      mass (BM) minus body fat. A force-velocity test on a cycle ergometer was used to
      measure CPP. CPP was related to anthropometric variables using standard and
      allometric models. CPP in absolute terms was higher in obese children than in
      lean children irrespective of gender. BM-related CPP was significantly lower in
      obese children than in lean ones, whereas no effect of obesity appeared on FFM
      related CPP. Velocity at CPP (Vopt) was significantly lower and force at CPP
      (Fopt) was significantly higher in girls than in boys. Muscle power production
      was unaffected by obesity in children. Low BM-related CPP could explain the
      difficulty of taking up physical activities that are body-mass related in obese
      children. Gender difference for Vopt and Fopt shows that girls and boys may have
      different maturation patterns affecting CPP.

PMID- 17510671
TI  - Conjugated linoleic acid increases skeletal muscle ceramide content and decreases
      insulin sensitivity in overweight, non-diabetic humans.
AB  - The effect of conjugated linoleic acid (CLA), a popular weight-loss supplement,
      on insulin sensitivity in humans is controversial and has not been extensively
      studied. To date no studies have examined the effects of CLA supplementation on
      human skeletal muscle metabolism or lipid content. It is also unknown whether CLA
      accumulates in human skeletal muscle with supplementation. In the present study,
      9 overweight, non-diabetic individuals received 4 g/d of mixed CLA isomers in the
      form of 1 g supplements, for 12 weeks. CLA isomers significantly increased in
      both plasma and skeletal muscle following supplementation. Skeletal muscle
      ceramide content was also significantly increased, although there was no
      consistent change in muscle diacylglycerol or triacylglycerol content. Insulin
      sensitivity was significantly decreased (p<or=0.05) following CLA
      supplementation, with a significant increase in glucose and insulin area under
      the curve during an oral glucose tolerance test (p<or=0.005). The protein content
      of PPARalpha, for which CLA is a potent ligand, was unchanged following
      supplementation. Accordingly, there was no change in markers of muscle oxidative
      capacity. In conclusion, mixed-isomer CLA supplementation in overweight non
      diabetic humans results in the accumulation of CLA and ceramide in skeletal
      muscle, and decreases insulin sensitivity.

PMID- 17510672
TI  - Pulmonary O2 uptake on-kinetics in sprint- and endurance-trained athletes.
AB  - Pulmonary O2 uptake kinetics during "step" exercise have not been characterized
      in young, sprint-trained (SPT), athletes. Therefore, the objective of this study
      was to test the hypotheses that SPT athletes would have (i) slower phase II
      kinetics and (ii) a greater oxygen uptake "slow component" when compared with
      endurance-trained (ENT) athletes. Eight sub-elite SPT athletes (mean (+/-SD)
      age=25 (+/-7) y; mass=80.3 (+/-7.3) kg) and 8 sub-elite ENT athletes (age=28 (+/
      4) y; mass=73.2 (+/-5.1) kg) completed a ramp incremental cycle ergometer test, a
      Wingate 30 s anaerobic sprint test, and repeat "step" transitions in work rate
      from 20 W to moderate- and severe-intensity cycle exercise, during which
      pulmonary oxygen uptake was measured breath by breath. The phase II oxygen uptake
      kinetics were significantly slower in the SPT athletes both for moderate (time
      constant, tau; SPT 32 (+/-4) s vs. ENT 17 (+/-3) s; p<0.01) and severe (SPT 32
      (+/-12) s vs. ENT 20 (+/-6) s; p<0.05) exercise. The amplitude of the slow
      component (derived by exponential modelling) was not significantly different
      between the groups (SPT 0.55 (+/-0.12) L.min(-1) vs. ENT 0.50 (+/-0.22) L.min(
      1)), but the increase in oxygen uptake between 3 and 6 min of severe exercise was
      greater in the SPT athletes (SPT 0.37 (+/-0.08) L.min(-1) vs. ENT 0.20 (+/-0.09)
      L.min(-1); p<0.01). The phase II tau was significantly correlated with indices of
      aerobic exercise performance (e.g., peak oxygen uptake (moderate-intensity r=
      0.88, p<0.01; severe intensity r=-0.62; p<0.05), whereas the relative amplitude
      of the oxygen uptake slow component was significantly correlated with indices of
      anaerobic exercise performance (e.g., Wingate peak power output; r=0.77; p<0.01).
      Thus, it could be concluded that sub-elite SPT athletes have slower phase II
      oxygen uptake kinetics and a larger oxygen uptake slow component compared with
      sub-elite ENT athletes. It appears that indices of aerobic and anaerobic exercise
      performance differentially influence the fundamental and slow components of the
      oxygen uptake kinetics.

PMID- 17510674
TI  - Trends in physical activity research in Canada.
AB  - The purpose of this study was to assess Canada's physical activity research
      productivity by (i) assessing Canada's contribution to global physical activity
      research, (ii) determining trends in Canadian physical activity research over
      time, and (iii) identifying research areas of greater or lesser representation. A
      Medline search was performed to identify physical activity research published
      between 1990 and 2005 from Canadian institutions or using Canadian data. Trends
      over time were plotted and compared with global physical activity research
      patterns. Original and review articles were sorted based on subject
      characteristics, nature of physical activity contribution, province and
      institution of origin, and research area or "pillar". A total of 5302 Canadian
      physical activity articles were identified for the period 1990-2005, representing
      4.9% of global physical activity research. After manual sorting of abstracts,
      3829 relevant articles were included for further analysis. A majority of Canada's
      physical activity research has come from Ontario (49%), followed by Quebec (21%),
      Alberta (10%), and British Columbia (10%). Where physical activity was the
      primary research focus, the biomedical and clinical pillars each accounted for
      39% of Canadian research, with lesser contributions from population health (14%)
      and health services (2%). Physical activity research productivity in Canada has
      paralleled global trends over the last 15 years. There is currently less physical
      activity research being conducted in population health and health services than
      in the biomedical and clinical areas; however, these areas play an important role
      in the development of public health policy and programs targeted at reducing the
      burden of physical inactivity and obesity in Canada.

PMID- 17510673
TI  - Relationship between metabolic function and skeletal muscle fatigue during a 90 s
      maximal isometric contraction.
AB  - Little is known concerning the contributions of oxidative phosphorylation
      (OxPhos), anaerobic glycolytic rate (AnGly), maximum creatine kinase (CK)
      activity, and metabolic economy (ME) on fatigue resistance. The purpose of this
      study was to model fatigue using muscle tissue metabolic measures during a
      maximal short-duration isometric contraction. Muscle metabolic function was
      measured with [31P]-magnetic resonance spectroscopy (MRS) in 54 premenopausal
      women (age: 33.8+/-6.3 y) while they performed 100% isometric plantar flexions.
      Multiple regression analysis revealed that all metabolic variables were
      independent predictors of fatigue resistance after adjusting for maximum
      isometric force generated (R2=0.56). ME accounted for the largest portion (36%)
      of overall shared variance. OxPhos accounted for the most shared variance of the
      three energy systems. These results support previous findings that OxPhos, AnGly,
      CK, and ME all contribute to fatigue resistance over a short duration.
      Additionally, the continued activity of CK at the end of 90 s of maximal exercise
      lends support to the concept of a CK shuttle facilitating energy transfer within
      the mitochondria.

PMID- 17510675
TI  - The effect of pedometer position and normal gait asymmetry on step count
      accuracy.
AB  - Manufacturers of pedometers recommend wearing a pedometer on the midline of the
      right thigh and this recommendation is used in research. However, there is
      conflicting evidence regarding the effect of pedometer position on accuracy. The
      purpose of this study was to systematically evaluate the effect of pedometer
      position on accuracy for 3 modes of gait. The Yamax SW200 pedometer was evaluated
      in 20 subjects in 5 different positions simultaneously: left mid-axillary, left
      mid-thigh, umbilical, right mid-thigh, and right mid-axillary. Each subject was
      asked to walk on a treadmill (54, 80, and 107 m.min(-1)), to walk overground
      (slow, preferred, and fast speeds), and to ascend and descend stairs. Pedometer
      steps were recorded and compared with actual steps observed. Using the same
      protocol, instantaneous triaxial accelerometry was used to explain position
      dependent differences in accuracy. At slow speeds, the left mid-axillary position
      demonstrated the lowest net mean (+/-SD) error across all modes of gait (7.7% (+/
      11.6%) overground;-0.6% (+/-2.2%) stairs). The right mid-thigh position had
      significantly (p<0.01) higher error for treadmill (18.1% (+/-17.3%)), overground
      (12.9% (+/-15.2%)), and stairs (2.9% (+/-3.9%)). Pedometer position dependent
      error was demonstrated, with the left mid-axillary position superior to the
      recommended position of right mid-thigh. The greater accuracy on the left side
      was wholly explained by gait asymmetry evident in step-induced accelerations
      recorded at right and left pedometer positions. A model of absolute error based
      on the ratio of steps at different gait speeds was generated to demonstrate the
      importance of this finding in pedometer-based lifestyle intervention studies.

PMID- 17510676
TI  - Influence of age and pubertal status on substrate utilization during exercise
      with and without carbohydrate intake in healthy boys.
AB  - Substrate utilization during exercise is known to differ between children and
      adults, but whether these differences are related to pubertal status is unclear.
      The objective of this study was to investigate the effects of pubertal status on
      endogenous (CHOendo) and orally ingested exogenous (CHOexo) carbohydrate and fat
      oxidation rates during exercise. Twenty boys at the same chronological age (12 y)
      were divided into three pubertal groups (pre-pubertal, PP: n=7; early-pubertal,
      EP: n=7; mid- to late-pubertal, M-LP: n=6) and consumed either a placebo or 13C
      enriched 6% CHO drink while cycling for 60 min at approximately 70% of their
      maximal aerobic power (VO2 max). Another group of 14-year-old boys (pubertal,
      n=9) completed all procedures. Substrate utilization was calculated for the final
      15 min of exercise using indirect calorimetry and stable isotope methodology.
      CHOexo decreased fat (p<0.001) and increased total CHO (p<0.001) oxidation,
      irrespective of group. Fat oxidation was higher (p=0.01) in younger boys than in
      older boys, but similar (p>or=0.33) among PP, EP, and M-LP boys. CHOexo
      contributed to approximately 30% of energy expenditure (EE) in PP and EP, but to
      only 24% in M-LP (p=0.02), which was identical to the older boys (24%). CHOexo
      oxidation rate as a percentage of EE was inversely related to testosterone levels
      (r=-0.51, p=0.005, n=29). It was concluded that reliance on CHOexo during
      exercise is particularly sensitive to pubertal status, with the highest oxidation
      rates observed in pre- and early-pubertal boys, independent of chronological age.

PMID- 17510677
TI  - No difference in insulin sensitivity between healthy postmenopausal women with or
      without sarcopenia: a pilot study.
AB  - Insulin plays a pivotal role in skeletal muscle protein metabolism and its action
      decreases with age. A loss of muscle mass, termed sarcopenia, also occurs with
      age. The age-associated decline in insulin sensitivity (IS) may negatively alter
      muscle protein metabolism and, therefore, be implicated in the aetiology of
      sarcopenia. However, no studies have yet compared the level of IS between older
      individuals with or without sarcopenia. Thus, in this study, we compared the IS
      of 20 class I sarcopenics (CIS), 8 class II sarcopeniscs (CIIS), and 16 non
      sarcopenics (NS), among a group of otherwise healthy, non-obese, postmenopausal
      women. IS was estimated with the quantitative IS check index (QUICKI). Muscle
      mass index (MMI), which was used to determine sarcopenia, was calculated as
      follows: (appendicular muscle massx1.19)-1.01/h2, where h=height. Fat-free mass
      (FFM), fat mass (FM), and trunk FM (TFM) were measured by dual-energy X-ray
      absorptiometry. Accelerometry and indirect calorimetry were used to estimate
      resting (REE), daily (DEE), and physical activity (PAEE) energy expenditure. A 3
      d food record was used to determine total energy, protein (animal and vegetal),
      and carbohydrate intakes. As expected, MMI and FFM differed significantly among
      groups. However, no significant differences were found among groups for IS, FM,
      TFM, REE, DEE, PAEE, or total energy, protein (both animal and vegetable), and
      carbohydrate intakes. Using QUICKI, a surrogate measure of IS, the present
      results suggest that the action of insulin does not play an important role in the
      development and maintenance of sarcopenia in healthy, non-obese, postmenopausal
      women.

PMID- 17510678
TI  - Manipulating training intensity and volume in already well-trained rats: effect
      on skeletal muscle oxidative and glycolytic enzymes and buffering capacity.
AB  - Well-trained endurance athletes undergo periods of high-intensity interval
      training (HIT) or high-volume training (HVT) to improve exercise performance, but
      little is known about the mechanistic changes that occur during this time. The
      purpose of this study was to examine the influence of HIT and HVT on the
      activities of citrate synthase (CS) and phosphofructokinase (PFK), and on
      intramuscular buffering capacity (betam) in already well-trained rats. At 4 weeks
      of age, Wistar rats were divided into sedentary (SED; n=18) and exercise training
      groups (n=38). Following a 10 week preliminary training program, trained rats
      were divided randomly into 3 further groups that completed 4 additional weeks of
      continued endurance (CON, n=14), high-intensity training (HIT, n=12), or high
      volume training (HVT, n=12). Soleus (SOL), red and white gastrocnemius (RG and
      WG), and red and white vastus (RV and WV) muscles were removed 24-48 h after a
      final run-to-fatigue performance test (30 m.min(-1) 25% grade) to determine the
      activities of CS, PFK, and betam. No differences in run time to exhaustion were
      found between the groups. However the HIT group possessed CS and PFK activities
      and betam in WV muscle that were 60%, 24%, and 10% higher, respectively (all
      p<0.05), compared with the HVT group; differences were not found between the HIT
      and CON groups. Although no differences in run performance were found, HIT
      compared with HVT in already well-trained rats resulted in significantly higher
      oxidative and glycolytic capacities of fast-contracting fibres. No differences
      were shown in fast-contracting muscle between HIT and CON.

PMID- 17510679
TI  - The influence of velocity of stretch-shortening contractions on muscle
      performance during chronic exposure: age effects.
AB  - Aging increases injury susceptibility and impairs the ability to adapt to
      repetitive exposures of mechanical loading. The objective of this research was to
      investigate if movement velocity affects muscle response to a chronic
      administration of stretch-shortening cycles (SSCs) differently in young vs. old
      rats. Dorsiflexor muscles of old (30 months, n=5) and young rats (12 weeks, n=6)
      were exposed 3 times/week for 4.5 weeks to a protocol of 80 maximal SSCs per
      exposure in vivo. Skeletal muscle response was characterized by high- (500
      degrees/s) and low- (60 degrees/s) velocity dynamic performance, which was
      evaluated using peak eccentric force, isometric pre-stretch force, eccentric
      force enhancement above the isometric pre-stretch force, negative work, and
      positive work. The performance of the young and old groups was not statistically
      different at the start of the exposure. By the end of the exposure, however, a
      statistical difference was noted-performance increased significantly in the young
      animals and decreased significantly in the old animals. The SSC velocity had a
      profound effect on muscle response. The young animals' high- and low-velocity
      performances increased during the chronic exposure period, whereas the old
      animals' performances declined. High-velocity performance increased more than low
      velocity performance in young animals. In contrast, old animals suffered the most
      loss in high-velocity performance over the chronic exposure period. A chronic
      exposure of SSCs results in a significant performance increase in young animals,
      and a significant performance decrease in old animals. These differences are more
      profound during high-velocity movements. These findings suggest that age may
      impair the ability of skeletal muscle to adapt to repetitive mechanical loading,
      particularly during high-velocity movements.

PMID- 17510680
TI  - Oxygen cost of the CF-DND fire fit test in males and females.
AB  - The Department of National Defence employs a work-related test circuit comprising
      10 various firefighting tasks (FF test) to assess the fitness of incumbent
      Canadian Forces firefighters. The main purpose of this study was to document the
      oxygen cost of the FF test over a wide range of performance times. These data
      were then used to predict the oxygen cost associated with the 8 min completion
      standard. Finally, we examined the influence of gender on selected physiological
      responses during the FF test. Thirty male and 23 female subjects practiced the
      test 3-5 times and then completed, in random order and on separate days, a
      maximal-effort trial while breathing with either a self-contained breathing
      apparatus (SCBA) or a portable metabolic measurement system (MMC). The breath-by
      breath gas exchange data from the MMC were collapsed into a single value that
      represented the average oxygen cost for each participant to complete the work
      simulation. To calculate the average VO2 associated with the 8 min completion
      time, separate regression lines for test duration and average VO2 were generated
      for males and females. Analyses of covariance (ANCOVA) revealed that the
      regression lines for the male and female groups coincided, therefore all data
      were collapsed. The resulting regression equation predicted that the average VO2
      associated with the 8 min standard was 34.1 (+/-4.0) mL.kg(-1).min(-1), and this
      value appears consistent with other research on the oxygen cost of firefighting.
      There was no evidence to suggest that the oxygen cost of meeting the 8 min
      standard was different for males or females.

PMID- 17510681
TI  - Muscle oxygenation during prolonged electrical stimulation-evoked cycling in
      paraplegics.
AB  - This study investigated cardiorespiratory responses and muscle oxygenation during
      prolonged electrical stimulation (ES)-evoked leg cycling in individuals with
      paraplegia (PARA). Four PARA and 6 able-bodied (AB) persons participated in this
      study. Subjects performed 10 min of passive cycling and 40 min of active cycling
      (PARA, ES cycling; AB, voluntary cycling) at workloads selected to elicit an
      equivalent oxygen uptake between groups. Cycling power output, cardiorespiratory
      responses, mechanical efficiency, and quadriceps muscle oxygenation (measured
      with near-infrared spectroscopy) were measured over the duration of the exercise.
      Oxygen uptake was similar in both groups during active cycling (PARA, 737+/-177
      mL.min(-1); AB, 840+/-90 mL.min(-1)). The cycling power output for PARA
      individuals commenced at 8.8 W, but varied considerably over 40 min. PARA
      individuals demonstrated markedly lower gross mechanical efficiency
      (approximately 1.3%) during ES cycling compared with AB individuals performing
      voluntary exercise (approximately 12.6%). During ES cycling, muscle oxygen
      saturation (SO2) decreased to approximately 72+/-19%, whereas SO2 during
      volitional cycling was unaltered from resting levels. Muscle oxygenated
      haemoglobin initially decreased (-23%) during ES cycling, but returned to resting
      levels after 10 min. Deoxygenated haemoglobin initially rose during the first 5
      min of ES cycling, and remained elevated by 28% thereafter. Upon cessation of ES
      cycling, lower-limb muscle oxygenation increased (+93%), suggesting reactive
      hyperaemia in PARA individuals after such exercise. During ES cycling, muscle
      oxygenation followed a different pattern to that observed in AB individuals
      performing voluntary cycling at an equivalent VO2. Equilibrium between oxygen
      demand and oxygen delivery was reached during prolonged ES cycling, despite the
      lack of neural adjustments of leg vasculature in the paralyzed lower limbs.

PMID- 17510682
TI  - Interaction of exercise training and n-3 fatty acid supplementation on
      postprandial lipemia.
AB  - The effect of combining omega-3 fatty acid (n-3 FA) supplementation and exercise
      training treatment on postprandial lipemia (PPL) has not been studied. The
      purpose of this study was to examine the interaction of n-3 FA and exercise
      training in attenuating PPL after a high-fat meal. Previously sedentary,
      overweight, subjects (n=22; 12 women, 10 men, BMI 26.6+/-0.7 kg/m2) were randomly
      assigned to one of two treatment groups: n-3 FA supplementation alone (FO, n=10)
      or n-3 FA supplementation plus exercise training (FO+ExTr, n=12). Both groups
      consumed 4 g/d n-3 FA, and one group also exercise trained for 45 min/d, 5d/week
      of brisk walking and (or) jogging at 60% VO2 max. Before and after 4 weeks of
      treatment, subjects performed a baseline PPL and a PPL following a single session
      of exercise (ExPPL). PPL was assessed by triglyceride (TG) area under the curve
      (AUC) and peak TG response (TGpeak). A two-way analysis of variance (ANOVA) with
      repeated measures was used to compare results from treatments for baseline and
      exercise trials. FO alone reduced PPL and Ex PPL, and FO+ExTr attenuated the
      ExPPL response measured as total AUC and TGpeak. There was no significant main
      effect for group or group by time interaction for baseline PPL or ExPPL. Fasting
      high-density lipoprotein cholesterol (HDL-C) and HDL2-C (i.e., subfraction 2)
      concentrations were significantly increased in the FO+ExTr group after the
      treatments. These results suggest that n-3 FA supplementation reduced PPL in
      sedentary subjects. Exercise training has no interference or additive effects
      with n-3 FA supplementation in attenuating PPL, but combined treatments may be
      additive in raising high-density lipoprotein cholesterol.

PMID- 17510683
TI  - Neither gender nor menstrual cycle phase influences exercise-induced lymphocyte
      apoptosis in untrained subjects.
AB  - Lymphocyte apoptosis increases following maximal exercise. Estrogen hormones (E2)
      have been shown to protect lymphocytes from apoptosis in vitro, but it is unknown
      whether they can attenuate the apoptotic response to maximal exercise. The
      purpose of this study was to examine the effect of menstrual cycle variation on
      exercise-induced lymphocyte apoptosis in humans following exercise. Untrained
      healthy young men and regularly menstruating women not using hormonal
      contraceptives volunteered for the study. Women performed a maximal effort
      treadmill test for VO2 max once in the follicular phase (FOL) and once in the mid
      luteal phase (ML) of their cycles. Men completed two VO2 max tests with periods
      of time between tests matched to those of the female subjects. Blood was
      collected before (PRE) and immediately after exercise (POST), and analyzed for
      apoptotic lymphocytes and estradiol. E2 concentrations in women were
      significantly greater during ML versus during FOL, both PRE and POST (p<0.0001).
      The percent of exercise-induced lymphocyte apoptosis was similar between women
      (23.2%+/-1.0%) and men (21.5%+/-0.4%). In women, the apoptotic response to
      maximal exercise was similar regardless of menstrual cycle phase (FOL=23.7%+/
      0.9%, ML=22.7%+/-1.1%). Although elevated female sex hormones in vitro may exert
      anti-apoptotic effects, these data suggest that in vivo concentrations confer no
      protection to lymphocytes during exhaustive exercise.

PMID- 17510688
TI  - Think tank on school-aged children: nutrition and physical activity to prevent
      the rise in obesity.
AB  - The rise in childhood obesity has generated concern across a range of sectors.
      Stakeholders and experts in the area of children's health met at a Think Tank in
      Toronto organized by the Canadian Council for Food and Nutrition and the Program
      in Food Safety, Nutrition, and Regulatory Affairs at the University of Toronto to
      discuss the current evidence in place to inform the development of school
      policies to reduce childhood obesity. Although there is some evidence to suggest
      that school interventions may reduce obesity in children, there are other
      examples of programs that have had very little impact. The role of parents in the
      development of healthy eating and physical activity patterns is critical from the
      earliest stages of life and warrants further attention. Delegates agreed that we
      need ongoing input of experts and leaders from all sectors and fields to help us
      to effectively promote healthy lifestyles at schools and within the home, while
      respecting each child's need for safety, security, and respect.

PMID- 17510689
TI  - Eat, run, and...shiver? From the exercise--diet and energy balance symposium at
      CSEP 2005.
AB  - This short introduction includes a brief description of papers that were prepared
      following the "Symposium on Exercise--Diet and Energy Balance", which was
      presented at the Canadian Society for Exercise Physiology annual meeting in the
      autumn of 2005. Briefly, these three papers discuss findings related to (i) the
      emerging role of exercise in the treatment of obesity and its co-morbidities,
      (ii) the role of novel proteins secreted by fat, and (iii) the control of
      appetite and food intake after successful weight loss.

PMID- 17510690
TI  - Environmental influences on adiponectin levels in humans.
AB  - In addition to its classic role in the storage and release of nonesterified fatty
      acids, the adipocyte is now recognized as a critical source of many endocrine
      signals. Of these signals, adiponectin has been found to promote lipid oxidation
      and glucose uptake in skeletal muscles and to reduce glucose output in the liver.
      Because of the effects of adiponectin on these organs, the search for factors or
      conditions that could positively influence the synthesis of this adipocyte
      derived protein has drawn a great deal of interest. This brief review explores
      the effects of environmental influences such as weight loss, acute food intake,
      exercise, and cold exposure on circulating adiponectin levels in humans.

PMID- 17510691
TI  - Physical activity in the treatment of obesity: beyond body weight reduction.
AB  - The prevalence of obesity is high and continues to increase. Obesity is a leading
      risk factor for premature mortality and numerous chronic health conditions. The
      role of physical activity as a treatment and (or) preventive strategy for
      combating obesity has been the subject of substantial research. Most of this
      research has focused solely on reductions in total body weight and (or) fat mass
      as the indicator of treatment success. Because the deposition of fat in the
      abdomen and nonadipose tissues of the liver and muscle plays a major role in the
      development of obesity-related health risk, these depots have emerged as
      alternative targets for obesity treatment. Absent from previous reviews is a
      detailed consideration of the influence of physical activity on these treatment
      outcomes. The purpose of this review is to evaluate the independent role of
      physical activity in the treatment of obesity in a broader context; that is,
      through its effects on abdominal obesity and liver and muscle fat, in addition to
      its established effects on body weight and (or) total fat mass. Consideration is
      also given to the utility of physical activity with minimal or no weight loss in
      the treatment of obesity.

PMID- 17510692
TI  - Appetite control after weight loss: what is the role of bloodborne peptides?
AB  - The literature presented in this paper argues that our limited ability to
      maintain energy balance in a weight-reduced state is the product of our
      difficulty in compensating for the weight loss-induced reduction in total energy
      expenditure. The end result, translated into the overwhelming complexity of
      preserving long-term weight loss, is presented as being a consequence of
      compromised appetite control. Given the present-day food landscape and the
      resultant susceptibility to passive overconsumption, the focus of this review
      will be on the peripheral ("bottom-up") signals (leptin, PYY, ghrelin, and GLP-1)
      and the evidence highlighting their influence on feeding behaviour. As we
      continue studying paradigms of body mass reduction, specifically the data
      emerging from patients of bariatric surgery, it is becoming clearer that counter
      regulatory adaptations, possibly through down-(leptin, PYY, and GLP-1) or
      upregulation (ghrelin) of peptides, have an impact on energy balance. In itself,
      food deprivation influences some of the peptides that ultimately provide the
      physiological input for the overt expression of feeding behaviour; these
      peripheral adaptations are expected to serve as feeding cues--cues that, in the
      end, can serve to compromise the maintenance of energy balance. In a potentially
      novel intervention to increase compliance to long-term reductions in energy
      intake, it is proposed that manipulating the pattern of food intake to favourably
      alter the profile of gastrointestinal peptides would lead to better dietary
      control.

PMID- 17510693
TI  - Physical activity and diabetes: current considerations.
AB  - The prevalence of diabetes is increasing rapidly. Overeating, leading to obesity
      and overweight, is often considered the main determinant of this increase.
      However, evidence is accumulating that physical inactivity may be as important a
      factor in the development of diabetes as being overweight. The reviews in this
      issue of Applied Physiology, Nutrition, and Metabolism discuss the current
      knowledge on the role of physical activity in the prevention and treatment of
      diabetes.

PMID- 17510694
TI  - Exercise, pregnancy, and insulin sensitivity--what is new?
AB  - Pregnancy is characterized by a marked physiological insulin resistance.
      Overweight and obesity or lack of physical activity can aggravate this reduced
      insulin sensitivity further. Increased insulin resistance has been associated
      with serious pregnancy complications, such as gestational diabetes mellitus (GDM)
      and pre-eclampsia. Recent studies clearly indicate that physical activity before
      and during pregnancy can reduce the risk of GDM and pre-eclampsia.

PMID- 17510695
TI  - The effect of exercise, training, and inactivity on insulin sensitivity in
      diabetics and their relatives: what is new?
AB  - Insulin resistance is a hallmark characteristic of type 2 diabetes. However, in
      healthy first-degree relatives of type 2 diabetics, insulin resistance is often
      present years before glucose intolerance or diabetes becomes clinically manifest.
      The mechanisms of insulin resistance involve conditions leading to an increased
      supply of fatty acids (e.g., high energy intake, obesity) and conditions in which
      the degradation/oxidation of muscular fatty acids is impaired. Several large
      scale studies have documented the fact that increased physical activity can
      reduce or at least postpone the development of type 2 diabetes, and low physical
      fitness is a clear independent risk factor for the development of type 2
      diabetes. The mechanisms responsible for the improvement in insulin sensitivity
      after exercise training have been studied extensively, but are not fully
      understood. This review focuses on insulin resistance in skeletal muscle and, in
      particular, its relation to changes in aerobic fitness in type 2 diabetics and
      their first-degree relatives.

PMID- 17510696
TI  - Strategies to enhance compliance to physical activity for patients with insulin
      resistance.
AB  - The evidence that physical activity is an effective therapeutic tool in the
      management of insulin resistance and type 2 diabetes is well documented. Limited
      research has addressed how best to promote and maintain physical activity in
      these individuals. This paper explores strategies to enhance compliance to
      physical activity for patients with insulin resistance. Several evidence-based
      guidelines and reviews recommend that physical activity interventions are based
      on a valid theoretical framework. However, there is no evidence-based consensus
      on the best theory or the combination of theories to use. Motivational tools such
      as pedometers, wearable sensors measuring energy expenditure, and point of choice
      prompts appear to be effective at stimulating short-term substantial increases in
      physical activity, but further strategies to maintain physical activity behaviour
      change are required. Physical activity consultation has demonstrated effective
      physical activity promotion over periods of up to 2 years in people with type 2
      diabetes. Future research should identify the longer term effects of this
      intervention and the effectiveness of different methods of delivery. Overall,
      there needs to be a lot more focus on this area of research. Without this, the
      abundance of research investigating the effects of physical activity on people
      with insulin resistance and type 2 diabetes is essentially redundant.

PMID- 17510697
TI  - Role of Akt substrate of 160 kDa in insulin-stimulated and contraction-stimulated
      glucose transport.
AB  - Insulin and exercise, the most important physiological stimuli to increase
      glucose transport in skeletal muscle, trigger a redistribution of GLUT4 glucose
      transporter proteins from the cell interior to the cell surface, thereby
      increasing glucose transport capacity. The most distal insulin signaling protein
      that has been linked to GLUT4 translocation, Akt substrate of 160 kDa (AS160),
      becomes phosphorylated in insulin-stimulated 3T3-L1 adipocytes; this is important
      for insulin-stimulated GLUT4 translocation and glucose transport. Insulin also
      induces a rapid and dose-dependent increase in AS160 phosphorylation in skeletal
      muscle. Available data from skeletal muscle support the concepts developed in
      adipocytes with regard to the role AS160 plays in the regulation of insulin
      stimulated glucose transport. In vivo exercise, in vitro contractions, or in situ
      contractions can also stimulate AS160 phosphorylation. AMP-activated protein
      kinase (AMPK) is likely important for phosphorylating AS160 in response to
      exercise/contractile activity, whereas Akt2 appears to be important for insulin
      stimulated AS160 phosphorylation in muscle. Evidence of a role for AS160 in
      exercise/contraction-stimulated glucose uptake is currently inconclusive. The
      distinct signaling pathways that are stimulated by insulin and
      exercise/contraction converge at AS160. Although AS160 phosphorylation is
      apparently important for insulin-stimulated GLUT4 translocation and glucose
      transport, it is uncertain whether elevated AS160 phosphorylation plays a similar
      role with exercise/contraction.

PMID- 17510698
TI  - Responses to acute exercise in type 2 diabetes, with an emphasis on metabolism
      and interaction with oral hypoglycemic agents and food intake.
AB  - In people with type 1 diabetes mellitis (DM), insulin administration, food
      intake, and exercise have to be carefully matched to avoid either hypo- or
      hyperglycemia. People with type 2 DM have some insulin secretion, which changes
      with needs. Accordingly, during exercise, these people do not run the same
      metabolic risks as people with type 1 DM. However, a contraction-mediated
      increase in glucose clearance in muscle is intact in type 2 DM. Therefore, in the
      postabsorptive state in diet-treated type 2 DM, a marked reduction in
      hyperglycemia can occur during prolonged moderate exercise. Sulfonylurea drugs
      augment the rate of decline in plasma glucose, because stimulation of insulin
      secretion reduces hepatic glucose production. After abstention from sulfonylurea
      for 5 days, the rate of decrease in plasma glucose with exercise is also
      enhanced, but from a higher glucose level. In the postabsorptive state, brief
      vigourous exercise elicits an increase in plasma glucose concentration,
      reflecting an exaggerated counterregulatory hormone response and glucose
      production. Moreover, insulin sensitivity is reduced in the early postexercise
      period. In the postprandial state, both prolonged moderate exercise and
      intermittent high-intensity exercise markedly decrease meal-induced increases in
      glucose, insulin, and C-peptide concentrations, whereas glucose appearance in
      plasma is unchanged. When exercise bouts are isocaloric, responses are identical,
      indicating that overall energy expenditure, and not peak exercise intensity, is
      the major determinant of exercise-induced changes in overall glucose homeostasis
      and insulin secretion in type 2 DM. Neither prolonged moderate nor intermittent
      high-intensity exercise performed in the postprandial state influences glucose or
      insulin responses to a subsequent meal. Finally, in people with type 2 DM, after
      a high-fat meal, prolonged moderate exercise reduces the exaggerated increases in
      plasma concentrations of triglycerides contained in chylomicrons and very low
      density lipoproteins.

PMID- 17510699
TI  - Type 1 diabetes: exercise and hypoglycemia.
AB  - The Diabetes Control and Complications Trial demonstrated that tight control of
      diabetes management greatly reduces the risk of microvascular complications of
      diabetes. Unfortunately, tight control of blood glucose can also result in
      hypoglycemia, especially in patients with type 1 diabetes mellitus (T1DM). It is
      now widely recognized that antecedent hypoglycemia can blunt neuroendocrine,
      autonomic nervous system (ANS), and metabolic counterregulatory responses to
      subsequent hypoglycemia. Thus, blunted counterregulatory defenses against falling
      plasma glucose levels are a major risk factor for hypoglycemia in people with
      diabetes. This risk is also complicated by a difference in responses between
      males and females. Because of the qualitative similarity of neuroendocrine, ANS,
      and metabolic responses to hypoglycemia and exercise, we developed studies to
      determine whether neuroendocrine and ANS counterregulatory dysfunction play a
      role in the pathogenesis of exercise-related hypoglycemia in T1DM. Results from
      these studies have shown that neuroendocrine (catecholamine and glucagon), ANS
      (muscle sympathetic nerve activity), and metabolic (lipolysis and glucose
      kinetics) responses are blunted during exercise after antecedent hypoglycemia,
      and that there is a sexual dimorphism in responses. Similarly, antecedent
      episodes of exercise can blunt counterregulatory responses during subsequent
      hypoglycemia, thereby creating reciprocal feed-forward vicious cycles that
      increase the risk of hypoglycemia during either stress.

PMID- 17510700
TI  - Epidemiological studies of exercise in diabetes prevention.
AB  - Type 2 diabetes is one of the fastest growing public health problems in both
      developed and developing countries. It is estimated that the number of people
      with diabetes in the world will double in coming years, from 171 million in 2000
      to 366 million in 2030. Cardiovascular disease accounts for more than 70% of
      total mortality among patients with type 2 diabetes. The associations of physical
      activity, physical fitness, and changes in the lifestyle with the risk of type 2
      diabetes have been assessed by a number of prospective studies and clinical
      trials in the past decade. Several studies have also evaluated the joint
      associations of physical activity, body mass index, and glucose levels with the
      risk of type 2 diabetes. Prospective studies and clinical trials have shown that
      moderate or high levels of physical activity or physical fitness and changes in
      the lifestyle (dietary modification and increase in physical activity) can
      prevent type 2 diabetes. Our review of the scientific evidence confirms that 30
      min/d of moderate- or high-level physical activity is an effective and safe way
      to prevent type 2 diabetes in all populations.

PMID- 17510701
TI  - A lifestyle intervention of weight-gain restriction: diet and exercise in obese
      women with gestational diabetes mellitus.
AB  - OBJECTIVE: This study assessed whether a weight-gain restriction regimen, with or
      without exercise, would impact glycemic control, pregnancy outcome, and total
      pregnancy weight gain in obese subjects with gestational diabetes mellitus (GDM).
      A total of 96 subjects with GDM met the inclusion criteria and were sequentially
      recruited, with 39 subjects self-enrolled in the exercise and diet (ED) group,
      and the remaining 57 subjects self-enrolled in the diet (D) group owing to
      contraindications or a lack of personal preference to exercise. All patients were
      provided a eucaloric or hypocaloric consistent carbohydrate meal plan and
      instructed in the self-monitoring of blood glucose. In addition, all ED subjects
      were prescribed an exercise routine equivalent to a 60% symptom-limited VO2 max.
      Subjects were followed at weekly or biweekly office visits. Results showed
      maternal weight and body mass index (35.2+/-7.2 (ED) vs. 33.5+/-9.2 (D)) at study
      entry as well as number of weeks into the study (7.7+/-5.7 (ED) vs. 9.4+/-4.7
      (D)) were similar in both the ED and D groups. Weight gain per week was
      significantly lower in the ED group than in the D group (0.1+/-0.4 kg vs. 0.3+/
      0.4 kg; p<0.05). Subjects (either ED or D) who gained weight had a higher
      percentage of macrosomic infants than those subjects who lost weight or had no
      weight change during pregnancy. Other pregnancy and fetal outcomes such as
      complications, gestational age at delivery, and rate of cesarean delivery were
      similar in both groups. Conclusions of this study were that caloric restriction
      and exercise result in limited weight gain in obese subjects with GDM, less
      macrosomic neonates, and no adverse pregnancy outcomes. Pregnancy is an ideal
      time for behaviour modification, and this intervention may also help promote long
      term healthy lifestyle changes.

PMID- 17510702
TI  - Other adaptations to training/inactivity in type 2 diabetics and other groups
      with insulin resistance: emphasis on prevention of CHD.
AB  - Physical training is recommended for the prevention and treatment of
      cardiovascular disease in the general population. In patients with type 2
      diabetes this is even more important, because the risk of clinical
      atherosclerotic disease is 2- to 3-fold that of nondiabetics and the survival
      rate is poorer. However, increased daily physical activity (e.g., walking for
      exercise) has been shown to reduce the risk of premature death from all causes
      and from cardiovascular disease in particular. The mechanism for the positive
      effect of physical training may be a reduction of known risk factors for
      atherosclerosis, but a direct effect on the atherosclerotic process per se cannot
      be excluded.

PMID- 17510704
TI  - Prostate cell differentiation status determines transient receptor potential
      melastatin member 8 channel subcellular localization and function.
AB  - In recent years, the transient receptor potential melastatin member 8 (TRPM8)
      channel has emerged as a promising prognostic marker and putative therapeutic
      target in prostate cancer (PCa). However, the mechanisms of prostate-specific
      regulation and functional evolution of TRPM8 during PCa progression remain
      unclear. Here we show, for the first time to our knowledge, that only secretory
      mature differentiated human prostate primary epithelial (PrPE) luminal cells
      expressed functional plasma membrane TRPM8 ((PM)TRPM8) channels. Moreover, PCa
      epithelial cells obtained from in situ PCa were characterized by a significantly
      stronger (PM)TRPM8-mediated current than that in normal cells. This (PM)TRPM8
      activity was abolished in dedifferentiated PrPE cells that had lost their luminal
      secretory phenotype. However, we found that in contrast to (PM)TRPM8, endoplasmic
      reticulum TRPM8 ((ER)TRPM8) retained its function as an ER Ca(2+) release
      channel, independent of cell differentiation. We hypothesize that the
      constitutive activity of (ER)TRPM8 may result from the expression of a truncated
      TRPM8 splice variant. Our study provides insight into the role of TRPM8 in PCa
      progression and suggests that TRPM8 is a potentially attractive target for
      therapeutic intervention: specific inhibition of either (ER)TRPM8 or (PM)TRPM8
      may be useful, depending on the stage and androgen sensitivity of the targeted
      PCa.

PMID- 17510705
TI  - PSGL-1-mediated activation of EphB4 increases the proangiogenic potential of
      endothelial progenitor cells.
AB  - Endothelial progenitor cell (EPC) transplantation has beneficial effects for
      therapeutic neovascularization; however, only a small proportion of injected
      cells home to the lesion and incorporate into the neocapillaries. Consequently,
      this type of cell therapy requires substantial improvement to be of clinical
      value. Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors
      and their ephrin ligands are key regulators of vascular development. We
      postulated that activation of the EphB4/ephrin-B2 system may enhance EPC
      proangiogenic potential. In this report, we demonstrate in a nude mouse model of
      hind limb ischemia that EphB4 activation with an ephrin-B2-Fc chimeric protein
      increases the angiogenic potential of human EPCs. This effect was abolished by
      EphB4 siRNA, confirming that it is mediated by EphB4. EphB4 activation enhanced P
      selectin glycoprotein ligand-1 (PSGL-1) expression and EPC adhesion. Inhibition
      of PSGL-1 by siRNA reversed the proangiogenic and adhesive effects of EphB4
      activation. Moreover, neutralizing antibodies to E selectin and P selectin
      blocked ephrin-B2-Fc-stimulated EPC adhesion properties. Thus, activation of
      EphB4 enhances EPC proangiogenic capacity through induction of PSGL-1 expression
      and adhesion to E selectin and P selectin. Therefore, activation of EphB4 is an
      innovative and potentially valuable therapeutic strategy for improving the
      recruitment of EPCs to sites of neovascularization and thereby the efficiency of
      cell-based proangiogenic therapy.

PMID- 17510706
TI  - Mature B cells class switched to IgD are autoreactive in healthy individuals.
AB  - Determination of the origin and fate of autoreactive B cells is critical to
      understanding and treating autoimmune diseases. We report that, despite being
      derived from healthy people, antibodies from B cells that have class switched to
      IgD via genetic recombination (and thus become class switched to C delta [C delta
      CS] cells) are highly reactive to self antigens. Over half of the antibodies from
      C delta-CS B cells bind autoantigens on human epithelioma cell line 2 (HEp-2)
      cells or antinuclear antigens, and a quarter bind double-stranded DNA; both
      groups of antibodies are frequently polyreactive. Intriguingly, some C delta-CS B
      cells have accumulated basic residues in the antibody variable regions that
      mediate anti-DNA reactivity via somatic hypermutation and selection, while other
      C delta-CS B cells are naturally autoreactive. Though the total percentage was
      appreciably less than for C delta-CS cells, a surprising 31% of IgG memory cell
      antibodies were somewhat autoreactive, and as expected, about 24% of naive cell
      antibodies were autoreactive. We interpret these findings to indicate either that
      autoreactive B cells can be induced to class switch to IgD or that autoreactive B
      cells that use IgD as the B cell receptor are not effectively deleted.
      Determination of the mechanism by which the majority of C delta-CS B cells are
      autoreactive may be important in understanding peripheral tolerance mechanisms
      and may provide insight into the enigmatic function of the IgD antibody.

PMID- 17510707
TI  - Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates
      cartilage erosion and promotes cartilage repair.
AB  - Aggrecan loss from cartilage in arthritis is mediated by aggrecanases.
      Aggrecanases cleave aggrecan preferentially in the chondroitin sulfate-2 (CS-2)
      domain and secondarily at the E(373) downward arrow(374)A bond in the
      interglobular domain (IGD). However, IGD cleavage may be more deleterious for
      cartilage biomechanics because it releases the entire CS-containing portion of
      aggrecan. Recent studies identifying aggrecanase-2 (ADAMTS-5) as the predominant
      aggrecanase in mouse cartilage have not distinguished aggrecanolysis in the IGD
      from aggrecanolysis in the CS-2 domain. We generated aggrecan knockin mice with a
      mutation that rendered only the IGD resistant to aggrecanases in order to assess
      the contribution of this specific cleavage to cartilage pathology. The knockin
      mice were viable and fertile. Aggrecanase cleavage in the aggrecan IGD was not
      detected in knockin mouse cartilage in situ nor following digestion with ADAMTS-5
      or treatment of cartilage explant cultures with IL-1 alpha. Blocking cleavage in
      the IGD not only diminished aggrecan loss and cartilage erosion in surgically
      induced osteoarthritis and a model of inflammatory arthritis, but appeared to
      stimulate cartilage repair following acute inflammation. We conclude that
      blocking aggrecanolysis in the aggrecan IGD alone protects against cartilage
      erosion and may potentiate cartilage repair.

PMID- 17510708
TI  - Disruption of erythroid K-Cl cotransporters alters erythrocyte volume and
      partially rescues erythrocyte dehydration in SAD mice.
AB  - K-Cl cotransport activity in rbc is a major determinant of rbc volume and
      density. Pathologic activation of erythroid K-Cl cotransport activity in sickle
      cell disease contributes to rbc dehydration and cell sickling. To address the
      roles of individual K-Cl cotransporter isoforms in rbc volume homeostasis, we
      disrupted the Kcc1 and Kcc3 genes in mice. As rbc K-Cl cotransport activity was
      undiminished in Kcc1(-/-) mice, decreased in Kcc3(-/-) mice, and almost
      completely abolished in mice lacking both isoforms, we conclude that K-Cl
      cotransport activity of mouse rbc is mediated largely by KCC3. Whereas rbc of
      either Kcc1(-/-) or Kcc3(-/-) mice were of normal density, rbc of Kcc1(-/-)Kcc3(
      /-) mice exhibited defective volume regulation, including increased mean
      corpuscular volume, decreased density, and increased susceptibility to osmotic
      lysis. K-Cl cotransport activity was increased in rbc of SAD mice, which are
      transgenic for a hypersickling human hemoglobin S variant. Kcc1(-/-)Kcc3(-/-) SAD
      rbc lacked nearly all K-Cl cotransport activity and exhibited normalized values
      of mean corpuscular volume, corpuscular hemoglobin concentration mean, and K(+)
      content. Although disruption of K-Cl cotransport rescued the dehydration
      phenotype of most SAD rbc, the proportion of the densest red blood cell
      population remained unaffected.

PMID- 17510711
TI  - The use of endodontically treated teeth as abutments for crowns, fixed partial
      dentures, or removable partial dentures: a literature review.
AB  - Endodontically treated teeth are commonly required to serve as abutments for
      crowns, fixed partial dentures, or removable partial dentures. Many clinicians
      are of the opinion that endodontically treated teeth do not serve as well as
      vital teeth. This article reviews the pertinent literature and seeks to reach a
      consensus for the use of endodontically treated teeth with each type of
      prosthesis. With appropriate preparation designs, endodontically treated teeth
      can serve well as abutments for crowns. As restorations become more complex and
      involve edentulous spans, some reservations apply. In some fixed partial denture
      designs, the use of endodontically treated teeth may be contraindicated.

PMID- 17510709
TI  - Acute exercise increases triglyceride synthesis in skeletal muscle and prevents
      fatty acid-induced insulin resistance.
AB  - Fatty acid oversupply is a key mediator of skeletal muscle insulin resistance in
      obesity, primarily via accumulation of fatty acid metabolites and activation of
      proinflammatory pathways. Herein, we demonstrate that fatty acid-induced insulin
      resistance in humans is completely prevented the day after 1 session of endurance
      exercise. Because skeletal muscle is the primary site for systemic glucose
      disposal and is highly susceptible to impaired insulin action by elevated fatty
      acid availability, we obtained skeletal muscle samples to investigate possible
      mechanisms mediating this protective effect of exercise. Prevention of fatty acid
      induced insulin resistance after exercise accompanied enhanced skeletal muscle
      protein expression of key lipogenic enzymes and an increase in muscle
      triglyceride synthesis. Partitioning more fatty acids toward triglyceride
      synthesis within muscle reduced the accumulation of fatty acid metabolites and
      suppressed the proinflammatory response in skeletal muscle, as evidenced by
      decreased phosphorylation and activation of JNK and increased abundance of
      inhibitor of NF-kappaB alpha (I kappa B-alpha) and I kappa B-beta. We believe
      this is the first study to demonstrate that 1 session of exercise completely
      reverses fatty acid-induced insulin resistance in humans. Reversal of insulin
      resistance accompanied enhanced lipogenic capacity within skeletal muscle,
      reduced accumulation of highly bioactive fatty acid metabolites, and suppressed
      activation of proinflammatory pathways known to impair insulin action.

PMID- 17510710
TI  - Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal
      muscle and protects against fat-induced insulin resistance.
AB  - Increased fat deposition in skeletal muscle is associated with insulin
      resistance. However, exercise increases both intramyocellular fat stores and
      insulin sensitivity, a phenomenon referred to as "the athlete's paradox". In this
      study, we provide evidence that augmenting triglyceride synthesis in skeletal
      muscle is intrinsically connected with increased insulin sensitivity. Exercise
      increased diacylglycerol (DAG) acyltransferase (DGAT) activity in skeletal
      muscle. Channeling fatty acid substrates into TG resulted in decreased DAG and
      ceramide levels. Transgenic overexpression of DGAT1 in mouse skeletal muscle
      replicated these findings and protected mice against high-fat diet-induced
      insulin resistance. Moreover, in isolated muscle, DGAT1 deficiency exacerbated
      insulin resistance caused by fatty acids, whereas DGAT1 overexpression mitigated
      the detrimental effect of fatty acids. The heightened insulin sensitivity in the
      transgenic mice was associated with attenuated fat-induced activation of DAG
      responsive PKCs and the stress mediator JNK1. Consistent with these changes,
      serine phosphorylation of insulin receptor substrate 1 was reduced, and Akt
      activation and glucose 4 membrane translocation were increased. In conclusion,
      upregulation of DGAT1 in skeletal muscle is sufficient to recreate the athlete's
      paradox and illustrates a mechanism of exercise-induced enhancement of muscle
      insulin sensitivity. Thus, increasing muscle DGAT activity may offer a new
      approach to prevent and treat insulin resistance and type 2 diabetes mellitus.

PMID- 17510712
TI  - Interfacial morphology of self-etching adhesive systems in dentin.
AB  - OBJECTIVE: To portray and assess the interfacial morphology achieved with self
      etching systems in dentin under observation by scanning electron microscopy.
      METHOD AND MATERIALS: Ten caries-free extracted erupted human third molars were
      used in this study. The occlusal enamel was removed, and 10 dentin disks with a
      thickness of 800 +/- 200 Microm were obtained by slow-speed sectioning with a
      diamond saw parallel to the occlusal surface. A standard smear layer was created
      on the occlusal surface by wet sanding with 600-grit sandpaper for 60 seconds.
      The dentin disks were randomly assigned to one of the systems: AdheSE (Ivoclar
      Vivadent), Optibond Solo Plus-Self-Etch (Kerr), Tyrian SPE (Bisco) as self
      etching primers, and Adper Prompt Self-Etch (3M Espe) and One-Up Bond F
      (Tokuyama) as self-etching adhesives. All systems were applied according to the
      manufacturers' instructions. After application of the adhesive systems, a 1.0-mm
      thick layer of a flowable composite resin (Filtek Flow; 3M Espe) was applied to
      the treated dentin surface and light cured for 40 seconds. The specimens were
      then processed for observation by scanning electron microscopy. RESULTS: All self
      etching systems achieved the formation of sealed interfaces and hybridized areas
      with variable extents except for the self-etching adhesive One-Up Bond F, which
      showed some gap formation and poor hybridization. Optibond Solo Plus-Self-Etch
      presented a more consistent adhesive interface with thicker hybrid layers,
      numerous resin tags, and lateral branches. CONCLUSION: Regarding the
      micromorphology aspect, Optibond Solo Plus-Self-Etch showed the finest result,
      while One-Up Bond F was not able to produce a satisfactory ultrastructural
      morphology.

PMID- 17510713
TI  - Resistance to fracture of crowned endodontically treated premolars restored with
      ceramic and metal post systems.
AB  - OBJECTIVES: The objective of this study was to assess the resistance to fracture
      of crowned endodontically treated premolars with varying ceramic and metal post
      systems under simulated occlusal load. METHOD AND MATERIALS: The study consisted
      of 60 extracted intact premolars with similar root diameter and length. Teeth
      were divided equally into 4 groups (n = 15) and prepared for posts and cast
      crowns as follows: group 1 = preformed metal post, composite core, and cast
      crown; group 2 = cast post and core and cast crown; group 3 = zirconia post,
      composite core, and cast crown; and group 4 = zirconia post and heat-pressed
      ceramic core and cast crown. All prepared teeth had 2 mm of sound dentin on which
      the cast crowns were cemented. A continuous load (kg) was applied by an Instron
      testing machine to the buccal cusp at a 30-degree angle to the long axis of each
      tooth at a crosshead speed of 2 mm/min until failure. One-way analysis of
      variance with Scheffe test was used to statistically compare the differences
      between groups. RESULTS: Mean failure loads (in newtons) for the 4 test groups
      were as follows: 1,103.3 (group 1), 1,234.5 (group 2), 826.6 (group 3), and 870.6
      (group 4). No significant difference in failure load values was found among all
      tested groups (F[3,59] = 2.05; P >.05). The primary mode of failure (85%) in all
      groups was an oblique radicular fracture, either apical to the post or at the
      post level. Horizontal fracture (15% to 20%) of the root and post was found in
      groups 3 and 4. CONCLUSION: Within the limitations of this study, varying ceramic
      and metal post systems did not affect the failure resistance of teeth restored
      with full-coverage cast metal crowns, under simulated occlusal load.

PMID- 17510714
TI  - Endodontic treatment of dens in dente associated with a chronic periapical lesion
      using an apical plug of mineral trioxide aggregate.
AB  - Dens in dente is a developmental anomaly that predisposes the tooth to develop
      caries and pulp periapical pathologies. A chronic lesion can develop without any
      clinical symptoms of the pathology. The purpose of this case report is to
      describe the endodontic treatment of dens in dente associated with a periapical
      lesion using a mineral trioxide aggregate apical plug.

PMID- 17510715
TI  - Effect of occlusal splints on the electromyographic activities of masseter and
      temporal muscles during maximum clenching.
AB  - OBJECTIVES: Despite the broad use of occlusal splints in the treatment of
      temporomandibular disorders, the efficacy of splints is a source of controversy.
      In this study, the effectiveness of occlusal splints on the electromyographic
      activity of the masseter and temporal muscles in healthy individuals was
      investigated. METHOD AND MATERIALS: An occlusal splint was made for 25 healthy
      individuals. Surface electromyographic recordings were done during maximum
      clenching without the splint and immediately after application of the splint. The
      relative level of activity in the masseter and temporal muscles was quantified by
      means of activity index. Paired t test and Wilcoxon signed-rank tests were used
      for data analysis. RESULTS: The mean electromyographic activities of masseter and
      temporal muscles (in mV/s) were 0.7712 and 1.0488 without the splint and 0.8396
      and 0.9276 immediately after application of the splint. There was no significant
      difference between the electromyographic activities of both muscles before and
      after insertion of the splints. The activity index increased after application of
      the occlusal splints. This increase was also insignificant. CONCLUSION: Immediate
      application of occlusal splints has no significant effect on the activity of
      masseter and temporal muscles. It could decrease the relative activity of the
      temporal to the masseter muscle (increasing the activity index).

PMID- 17510716
TI  - Pulp responses to the application of a self-etching adhesive in human pulps after
      controlling bleeding with sodium hypochlorite.
AB  - OBJECTIVE: To evaluate the pulp response to direct capping with self-etching
      adhesive systems using sodium hypochlorite as a hemostatic agent. METHOD AND
      MATERIALS: Twenty-six human third molars scheduled for extraction were selected
      from undergraduate students of dentistry. Class I cavities with pulp exposures
      were performed. To control bleeding, 2.5% sodium hypochlorite was used for 20
      seconds, followed by washing with saline solution. The pulp exposures were capped
      with calcium hydroxide (n = 10) or adhesive system (n = 16). All cavities were
      restored with adhesive system and composite resin. Half of the samples of each
      capping material were extracted after 30 days and the remaining after 90 days.
      The samples were prepared for histological analysis (hematoxylin-eosin) and
      bacterial detection (Brown & Hopps) and evaluated according to standard ranking.
      Data were submitted to statistical analysis (Mann-Whitney test). RESULTS: There
      was a significant difference (P <.05) only in relation to dentin barrier
      formation. Pulps dressed with calcium hydroxide showed dentin barrier formation
      in all specimens, obliterating the exposure site. No inflammatory response was
      associated with material. In the experimental group, after 30 days, there was an
      attempt for healing with reparative dentin deposition, presenting a mild to
      moderate inflammatory infiltrate. Similar findings were found after 90 days,
      decreasing the inflammatory response. Bacteria were not detected in any specimen
      evaluated. Sodium hypochlorite was effective for hemostatic control. CONCLUSION:
      Calcium hydroxide produced better biological performance than the self-etching
      adhesive, and sodium hypochlorite did not interfere with the pulp repair.

PMID- 17510717
TI  - Effect of sprue design on the castability and internal porosity in pure titanium
      castings.
AB  - OBJECTIVE: The aim of the study was to evaluate the pure titanium castability and
      internal porosity with 3 different sprue designs. METHOD AND MATERIALS: The sprue
      designs selected were the conventional cylindrical, funnel-shaped, and sheet-form
      sprue formers. To evaluate the castability, the mesh monitor was chosen. Eight
      mesh patterns (14 3 14 mm) of 49 squares were attached to each type of sprue
      design. They were invested in titanium investment material and cast in a
      semiautomatic titanium casting machine. The titanium castings were evaluated by 2
      methods. One was the visual observation of the castings for completeness, and the
      second was the radiographic qualitative analysis for the location of the internal
      porosities. RESULTS: Data were analyzed with analysis of variance and Student t
      test for paired comparison among different sprue designs. According to analysis
      of variance, all sprue designs revealed a statistically significant difference at
      the 5% level of confidence (P <.05, F = 3.50). Mesh patterns attached to funnel
      shaped sprue designs showed better percentage castability values. CONCLUSION: For
      titanium, casting using a funnel-shaped sprue design displayed better castability
      values and less internal porosities in the castings.

PMID- 17510718
TI  - The effect of 2 different bleaching regimens on the surface roughness and
      hardness of tooth-colored restorative materials.
AB  - OBJECTIVE: The purpose of this in vitro study was to evaluate the effects of 10%
      carbamide peroxide (Vivastyle/Vivadent) and 6.5% hydrogen peroxide strip bands
      (Crest Professional Whitestrips) on the surface roughness and hardness of the 3
      different tooth-colored restoratives: an ormocer (Definite), a packable composite
      (Filtek P60), and a flowable composite (Filtek Flow). METHOD AND MATERIALS: A
      total of 48 specimens (10 mm in diameter and 2 mm thick) of each material were
      fabricated against a mylar surface. After being polished with Sof-Lex discs, they
      were randomly divided into 3 groups of 16 and treated as follows: group I was
      stored in distilled water at 37 degrees C for 2 weeks (control), group II was
      treated with Vivastyle for 2 hours per day for 2 weeks, and group III was treated
      with Whitestrips for 30 minutes twice a day for 2 weeks. For groups II and III,
      the specimens were stored in distilled water at 37 degrees C during the hiatus
      period. At the end of the test period, the specimens were first subjected to
      surface roughness and then to microhardness tests. The data were analyzed by
      Kruskal-Wallis and Mann-Whitney U tests. RESULTS: Both bleaching regimens
      increased the surface roughness of the materials (P <.05), but Whitestrips
      significantly increased the roughness of materials more than did Vivastyle (P
      <.05). Both bleaching regimens decreased significantly the hardness of tested
      materials except Filtek P60 (P <.05). CONCLUSION: Bleaching agents may affect the
      surface of existing restorations; therefore, they should not be used
      indiscriminately when tooth-colored restorations are present.

PMID- 17510719
TI  - Intravascular papillary endothelial hyperplasia and osteoma: a case report of an
      individual with 2 different pathologies.
AB  - Intravascular papillary endothelial hyperplasia (IPEH) is an unusual, benign, non
      neoplastic, vascular lesion characterized histologically by papillary fronds
      lined by proliferating endothelium. Osteoma is a benign osteogenic lesion
      characterized by proliferation of compact or cancellous bone. Osteoma of the
      maxillary sinus is an uncommon lesion. The purpose of this report is to present a
      case with 2 different lesions (intravascular papillary endothelial hyperplasia
      and osteoma) occurring at the same time in 1 patient that may or may not be
      related to each other and to stress the value of diagnostic imaging.

PMID- 17510720
TI  - Clinical evaluation of different gingival retraction cords.
AB  - OBJECTIVES: Impression techniques in restorative dentistry require displacement
      of gingival tissues to expose subgingival finish lines on tooth preparations.
      Retraction cords are commonly used for this purpose. Some cord systems include
      various medicaments, which may remain in the sulcus after retraction procedures.
      The purpose of this study was to determine whether any of the commonly used
      gingival retraction medicaments could influence the surface characteristics of
      the impression material and to evaluate the clinical performance of retraction
      cords. METHOD AND MATERIALS: Sixteen cord systems in various shapes, sizes, and
      medications were used in this study. The clinical performances of cords were
      evaluated with a blind experimental study design, according to predetermined
      criteria. Results were analyzed by using chi-square test and ordinal logistic
      regression analysis (P <.05). RESULTS: Statistically significant differences were
      found in all criteria among groups (P <.05). None of the materials investigated
      appeared to have any influence on the surface characterization of the polyvinyl
      siloxane impression material used. Better impression qualities were observed in
      groups with easy insertion, proper dilatation, less recurrent bleeding, and no
      remnants or fraying. Logistic regression analysis revealed that both retraction
      cord medicaments (odds ratio = 0.63, P = .00 <.05) and cord thicknesses (odds
      ratio = 2.09, P = .00 <.05) were important risk factors on the gingival margin
      quality. CONCLUSIONS: The applied gingival retraction cord systems had no
      influence on the surface characterization of the polyvinyl siloxane material
      tested. Gingival margin quality of the impression and clinical application
      procedures were affected by the retraction systems. Untreated, medium-braided,
      and epinephrine-impregnated cord systems were clinically successful. However, the
      potential systemic effects of epinephrine must be considered.

PMID- 17510721
TI  - Therapeutic seal of approximal incipient noncavitated carious lesions: technique
      and case reports.
AB  - Sealing of incipient carious lesions in occlusal surfaces has been shown to
      arrest the progression of the lesions. In this report, we describe for approximal
      surfaces with noncavitated incipient lesions the clinical procedures for sealant
      application illustrating this minimally invasive method with 3 clinical cases and
      scanning electron microscopic images.

PMID- 17510722
TI  - The pregnant patient: considerations for dental management and drug use.
AB  - The pregnant woman who presents for dental care requires special consideration.
      This article reviews physiologic changes associated with pregnancy and current
      considerations for the dental treatment of pregnant dental patients, as well as
      for pregnant dental professionals. The limitations and safety of commonly used
      drugs and anesthetics are discussed. Recommendations for prenatal oral counseling
      are presented.

PMID- 17510723
TI  - Satisfaction with oral status among adult school-attending Saudi women with and
      without posterior fixed partial dentures.
AB  - To conduct a preliminary investigation of the relationship between patient
      satisfaction with oral status and the presence of posterior fixed partial
      dentures (FPD). METHOD AND MATERIALS: A total of 150 women with intact anterior
      dental segments, randomly drawn from women's schools for adult education,
      participated (mean age, 33.8 years; SD, 10.4; range, 20 to 63 years). Each woman
      was assisted in completing a questionnaire on aspects of her oral health beliefs
      and satisfaction with oral function, and underwent an on-site clinical
      examination. Subjects were categorized according to general prosthodontic status:
      those with missing posterior teeth and no FPDs (MN), those with FPDs (PR), and
      those who were fully dentate (FD). Their responses to the questionnaire were
      compared. RESULTS: Value placed on oral health did not differ among the groups.
      Satisfaction with overall oral status, chewing function, and appearance did not
      differ between MN and PR, although overall satisfaction and appearance were each
      significantly greater in FD than in MN (P <.001 and P <.05, respectively).
      Overall satisfaction was negatively correlated with the mean number of missing
      teeth (P <.01), although perception of chewing ability did not differ among the
      groups, nor did it differ in relation to the number of posterior occluding pairs
      of teeth. CONCLUSIONS: The hypothesis that individuals with fixed prosthodontic
      replacements of their missing posterior teeth are more satisfied with their oral
      status than those without such replacements was not confirmed, while the question
      of the importance of patient satisfaction as a positive outcome of oral health
      care is raised.

PMID- 17510724
TI  - Oral sugar clearance and other caries-related factors of stimulated whole saliva
      in patients with secondary Sjogren syndrome.
AB  - OBJECTIVE: To compare oral sugar clearance, salivary flow rate, buffer capacity,
      salivary counts of mutans streptococci and lactobacilli in whole saliva, and root
      caries in subjects with secondary Sjogren syndrome with those of healthy
      subjects. METHOD AND MATERIALS: Twenty subjects with secondary Sjogren syndrome
      and 20 healthy subjects (age 30 to 55 years; all women) rinsed their mouth with a
      20% sucrose solution. Before the rinse and 2, 5, 10, and 30 minutes after the
      rinse, 2 paper disks were soaked with saliva, 1 under the tongue and 1 in the
      mandibular vestibule. The salivary sucrose concentration was determined
      enzymatically. The clearance time and the area under the sugar clearance curve
      (AUC) were calculated. RESULTS: Patients with secondary Sjogren syndrome and with
      low salivary flow had longer sugar clearance times in the mandibular buccal
      vestibule and sublingual regions than did healthy individuals (P = .000 and P =
      .000, respectively). Significant differences of AUC values between the groups for
      the buccal and sublingual regions were also found (P = .000 and P = .003,
      respectively). CONCLUSION: Subjects with secondary Sjogren syndrome had longer
      sugar clearance time, related to low salivary flow, high counts of cariogenic
      microorganisms, and decayed and filled surfaces in the root.

PMID- 17510725
TI  - A unique treatment of finger-sucking habit in children with mental retardation:
      report of 2 cases.
AB  - Finger-sucking habit, or nonnutritive sucking, usually ceases spontaneously in
      childhood. If the habit is not broken, however, not only will dental occlusion be
      affected, but the shape of the finger may be altered as well. When the habit is
      broken, the threatening disturbances of digital growth and dental occlusion will
      resolve spontaneously. This article describes a unique type of habit-breaking
      appliance applied on the sucked fingers of 2 children with mental retardation.
      The advantages of this type of extraoral appliance are discussed.

PMID- 17510726
TI  - Effect of dowel length on the retention of 2 different prefabricated posts.
AB  - OBJECTIVE: To compare in vitro the retentive values of stainless steel, parallel
      sided posts to quartz-fiber, tapered posts for 2 different dowel lengths (5 and
      10 mm). METHOD AND MATERIALS: Both post systems were cemented with a dual-cure
      adhesive resin cement. Single-rooted extracted human teeth (n = 40) were
      decoronated and randomly divided into 4 groups of 10 samples each. Posts of 5 and
      10 mm in length were luted with the resin cement. Each sample was placed on a
      universal testing machine, and using a push-out method, a vertical load was
      applied at a crosshead speed of 2 mm/min. The amount of force required to
      dislodge the post was recorded. The effect of post type and length was evaluated
      using a 2-way analysis of variance. RESULTS: A statistically significant main
      effect was found for post length (P <.001), with the 10-mm posts of both post
      systems requiring greater force to dislodge than the 5-mm posts. There was no
      interaction between post length and post type (P >.05). CONCLUSION: It is
      concluded from this study that there is no statistical difference in retention
      between quartz-fiber, tapered posts and stainless steel, parallel-sided posts
      when they are cemented with the same resin cement (P >.05). The study also
      concludes that adequate retentive values are achieved with both post systems at
      the shorter, 5-mm post length.

PMID- 17510727
TI  - The marginal fit of porcelain veneers on titanium copings: an in vitro study.
AB  - OBJECTIVES: To compare the cervical microleakage of titanium copings veneered
      with 3 porcelain-based materials with that of titanium copings veneered with 2
      indirect polymeric materials. METHOD AND MATERIALS: Commercially pure, grade 2
      titanium was veneered with 3 porcelain systems specially designed for fusing on
      titanium: Ti22 (Noritake), Triceram (Esprident), and Vitatitankeramik (Vita).
      Additionally, 2 polymeric materials were used for veneering titanium: Chromasit
      and Targis (Ivoclar). Four veneer crowns for each titanium-veneer combination
      were obtained. After storing the specimens in basic fuchsin, the microleakage
      between titanium and veneer in the cervical area was assessed by measuring the
      extent of dye penetration within the interface. ANOVA and post hoc statistics
      were used to analyze the data. RESULTS: Chromasit exhibited the highest mean
      microleakage score (3 +/- 0.816). The least mean microleakage at the interface
      was recorded for Ti22 porcelain (0 +/- 0.0), followed by Triceram (0.25 +/-
      0.50), Vitatitankeramik (0.75 +/- 0.957), and Targis (1.5 +/- 1.732). Only the
      differences between each porcelain system and Chromasit were significant (P
      <.05). CONCLUSION: Within the limitations of this in vitro study, there was no
      significant microleakage between titanium copings and the porcelain veneers,
      regardless of the porcelain system. The microleakage between titanium and the
      polymeric materials depended on the veneering material. Leakage was significantly
      higher when Chromasit was used.

PMID- 17510728
TI  - Influence of cavity preparation and curing method on the marginal seal of resin
      composite restorations: an in vitro evaluation.
AB  - OBJECTIVE: To evaluate the influence of cavity design and photocuring method on
      the marginal seal of resin composite restorations. METHOD AND MATERIALS: Seventy
      two bovine teeth were divided into 2 groups: group 1 received box-type cavity
      preparations, and group 2 received plate-type preparations. Each group was
      divided into 3 subgroups. After etching and bonding, Z250 resin composite (3M
      Espe) was applied in 2 equal increments and cured with 1 of 3 techniques: (1)
      conventional curing for 30 seconds at 650 mW/cm2; (2) 2-step photocuring, in
      which the first step was performed 14 mm from the restoration for 10 seconds at
      180 mW/cm2 and the second step was performed in direct contact for 20 seconds at
      650 mW/cm2; or (3) progressive curing using Jetlite 4000 (J. Morita) for 8
      seconds at 125 mW/cm2 and then 22 seconds at 125 mW/cm2 up to 500 mW/cm2. The
      specimens were thermocycled for 500 cycles and then submitted to dye penetration
      with a 50% silver nitrate solution. Microleakage was assessed using a
      stereomicroscope. Data were analyzed using analysis of variance and Tukey test
      (5% level of significance). RESULTS: A statistically significant difference was
      found between groups when a double interaction between photocuring and cavity
      preparation was considered (P = .029). CONCLUSIONS: No one type of cavity
      preparation or photocuring method prevented micro-leakage. The plate-type
      preparation showed the worst dye penetration when conventional and progressive
      photocuring methods were used. The best results were found using the 2-step
      photocuring with the plate-type preparation.

PMID- 17510729
TI  - Enantioselective degradation and chiral stability of phenthoate in soil.

PMID- 17510730
TI  - Kainate receptor-mediated presynaptic inhibition converges with presynaptic
      inhibition mediated by Group II mGluRs and long-term depression at the
      hippocampal mossy fiber-CA3 synapse.
AB  - Kainate receptors (KARs) effect depression of glutamate release at hippocampal
      mossy fiber-CA3 (MF-CA3) synapses by a metabotropic action involving adenylyl
      cyclase (AC) inhibition, cAMP reduction, and diminished protein kinase A (PKA)
      activation. Using hippocampal slices, we show here that KAR activation interferes
      with the depression of glutamate release produced by Group II metabotropic
      glutamate receptor stimulation and low frequency stimulation (LFS)-induced long
      term depression (LTD), also expressed through presynaptic AC/cAMP/PKA at MF-CA3
      synapses. The mutual occlusion of depression mediated by presynaptic KARs, Group
      II mGluR and LFS-induced LTD suggests their mechanistic convergence at the MF-CA3
      synapse and thus invokes KARs in synaptic plasticity manifest in LTD.

PMID- 17510731
TI  - Intrathecal application of neuroectodermally converted stem cells into a mouse
      model of ALS: limited intraparenchymal migration and survival narrows therapeutic
      effects.
AB  - Stem and progenitor cells provide a promising therapeutic strategy for
      amyotrophic lateral sclerosis (ALS). To comparatively evaluate the therapeutic
      potentials of human bone marrow-derived mesodermal stromal cells (hMSCs) and
      umbilical cord blood cells (hUBCs) in ALS, we transplanted hMSCs and hUBCs and
      their neuroectodermal derivatives (hMSC-NSCs and hUBC-NSCs) into the ALS mouse
      model over-expressing the G93A mutant of the human SOD1 gene. We used a
      standardized protocol similar to clinical studies by performing a power
      calculation to estimate sample size prior to transplantation, matching the
      treatment groups for gender and hSOD-G93A gene content, and applying a novel
      method for directly injecting 100,000 cells into the CSF (the cisterna magna).
      Ten days after transplantation we found many cells within the subarachnoidal
      space ranging from frontal basal cisterns back to the cisterna magna, but only a
      few cells around the spinal cord. hMSCs and hMSC-NSCs were also located within
      the Purkinje cell layer. Intrathecal cell application did not affect survival
      times of mice compared to controls. Consistently, time of disease onset and first
      pareses, death weight, and motor neuron count in lumbar spinal cord did not vary
      between treatment groups. Interestingly, transplantation of hMSCs led to an
      increase of pre-symptomatic motor performance compared to controls in female
      animals. The negative outcome of the present study is most likely due to
      insufficient cell numbers within the affected brain regions (mainly the spinal
      cord). Further experiments defining the optimal cell dose, time point and route
      of application and particularly strategies to improve the homing of transplanted
      cells towards the CNS region of interest are warranted to define the therapeutic
      potential of mesodermal stem cells for the treatment of ALS.

PMID- 17510732
TI  - Features of probable multiple system atrophy patients identified among 4770
      patients with parkinsonism enrolled in the multicentre registry of the German
      Competence Network on Parkinson's disease.
AB  - We identified 221 patients with probable multiple system atrophy (MSA) among 4770
      patients enrolled in the multicentre registry of the German Competence Network on
      Parkinson's disease (PD) according to the established consensus criteria to
      characterize their clinical presentation. Analyses of more than 100 recorded
      clinical items revealed several specifics: I) 50% of patients with probable MSA
      had asymmetry of symptoms at disease onset and tremor at rest was present in 25%;
      II) a positive response to levodopa was recorded in 51% of patients identified
      initially with severe autonomic failure and cerebellar ataxia; III) a positive
      family history was recorded in 11% (n = 23), two of these patients were
      identified with spinocerebellar ataxia type 3 (SCA3). Thus asymmetry of symptoms,
      tremor at rest and a positive response to levodopa are not as specific for
      idiopathic PD as believed previously. Patients with SCA3 may present with the
      clinical features of MSA.

PMID- 17510733
TI  - Gait and dementia: moving beyond the notion of gait apraxia.
AB  - Highest level gait disorders are produced by pathology in one or more structures
      in the cortical-basal ganglia-thalamocortical loop, which plays an important role
      in producing movements and postural synergies that meet personal desires and
      environmental constraints. Virtually all patients with dementia have pathology in
      one or more components of this loop, so highest level gait disorders are common
      in patients with dementia. The terminology surrounding these gait disorders is
      unnecessarily complex and too heavily influenced by the controversial concept of
      gait apraxia. Straightforward descriptive diagnostic criteria are needed. To this
      end, four core clinical features of highest level gait disorders are proposed: 1)
      inappropriate (counterproductive) or bizarre limb movement, postural synergies,
      and interaction with the environment, 2) qualitatively variable performance,
      influenced greatly by the environment and emotion, 3) hesitation and freezing,
      and 4) absent or inappropriate (counterproductive) rescue reactions. These core
      features follow logically from the physiology of the cortical-basal ganglia
      thalamocortical loop and should be regarded as signs of pathology in this loop. A
      clinical rating scale based on these features should be developed to facilitate
      clinical diagnosis and clinicopathological correlation, while avoiding the
      ambiguities and controversies of gait apraxia.

PMID- 17510735
TI  - Organic solutes in Rubrobacter xylanophilus: the first example of di-myo-inositol
      phosphate in a thermophile.
AB  - The thermophilic and halotolerant nature of Rubrobacter xylanophilus led us to
      investigate the accumulation of compatible solutes in this member of the deepest
      lineage of the Phylum Actinobacteria. Trehalose and mannosylglycerate (MG) were
      the major compounds accumulated under all conditions examined, including those
      for optimal growth. The addition of NaCl to a complex medium and a defined medium
      had a slight or negligible effect on the accumulation of these compatible
      solutes. Glycine betaine, di-myo-inositol-phosphate (DIP), a new phosphodiester
      compound, identified as di-N-acetyl-glucosamine phosphate and glutamate were also
      detected but in low or trace levels. DIP was always present, except at the
      highest salinity examined (5% NaCl) and at the lowest temperature tested (43
      degrees C). Nevertheless, the levels of DIP increased with the growth
      temperature. This is the first report of MG and DIP in an actinobacterium and
      includes the identification of the new solute di-N-acetyl-glucosamine phosphate.

PMID- 17510736
TI  - Severe anal bleeding in Proteus syndrome: a case report.
AB  - Proteus syndrome was originally described by Cohen and Hayden in 1979. The
      disorder was named Proteus syndrome by Wiedmann and colleagues in 1983 after
      Proteus, the giant Greek god of the sea. Proteus syndrome is a rare, sporadic,
      congenital polymorphic condition. Approximately 200 cases have been reported in
      the literature, but none has been associated with anal bleeding from hemorrhoids.
      We describe the case of a 21-year-old man with Proteus syndrome with severe anal
      bleeding. A hemorrhoidectomy was assumed to be too risky because of the massive
      venous abnormalities seen on CT. The patient was successfully treated by Doppler
      guided haemorrhoidal artery ligation (DG-HAL). Six months after surgery, the
      patient has had no further episodes of anal bleeding.

PMID- 17510734
TI  - Adult neurogenesis in serotonin transporter deficient mice.
AB  - Serotonin (5-HT) is a regulator of morphogenetic activities during early brain
      development and neurogenesis, including cell proliferation, migration,
      differentiation, and synaptogenesis. The 5-HT transporter (5-HTT, SLC6A4)
      mediates high-affinity reuptake of 5-HT into presynaptic terminals and thereby
      fine-tunes serotonergic neurotransmission. Inactivation of the 5-HTT gene in mice
      reduces 5-HT clearance resulting in persistently increased concentrations of
      synaptic 5-HT. In the present study, we investigated the effects of elevated 5-HT
      levels on adult neurogenesis in the hippocampus of 5-HTT deficient mice,
      including stem cell proliferation, survival, and differentiation. Using an in
      vivo approach, we showed an increase in proliferative capacity of hippocampal
      adult neural stem cells in aged 5-HTT knockout mice (approximately 14.5 months)
      compared to wildtype controls. In contrast, in vivo and additional in vitro
      analyses of younger adult 5-HTT knockout mice (approximately 7 weeks and
      approximately 3.0 months) did not reveal significant changes in proliferation of
      neural stem cells or survival of newborn cells. We showed that the cellular fate
      of newly generated cells in 5-HTT knockout mice is not different with respect to
      the total number and percentage of neurons or glial cells from wildtype controls.
      Our findings indicate that elevated synaptic 5-HT concentration throughout early
      development and later life of 5-HTT deficient mice does not induce adult
      neurogenesis in adult mice, but that elevated 5-HT levels in aged mice influence
      stem cell proliferation.

PMID- 17510737
TI  - Mucinous adenocarcinoma derived from chronic perianal fistulas: report of a case
      and review of the literature.
AB  - Chronic perianal fistulas are a common clinical condition. However, their
      evolution into adenocarcinoma is rare. We report the case of a 68-year-old man
      with perineal and perianal chronic fistulas, who developed a perineal mass that
      extended proximally as a pararectal tumor. Diagnosis was confirmed by magnetic
      resonance imaging (MRI). Histopathological sections indicated extramucosal
      mucinous adenocarcinoma. No intestinal lesion was seen at endoscopic examination.
      The patient underwent abdominal perineal excision of the rectum without
      neoadjuvant or adjuvant therapy, and had a good postoperative outcome.

PMID- 17510738
TI  - The Noble plication: new indication for a historical procedure.
AB  - Complications following ileal pouch-anal anastomosis (IPAA) have been well
      described in the literature. While rare, small bowel volvulus following IPAA has
      been described. We describe the successful use of the modified Noble plication in
      such a patient with small bowel volvulus about an elongated mesentery. This
      largely 'historical' technique is well-suited to manage small bowel volvulus,
      especially when non-resectional management is preferred.

PMID- 17510739
TI  - A novel technique for rectocele repair in elderly women.
AB  - We have developed a transvaginal technique for rectocele repair which we believe
      to be particularly suitable for older woman. A transverse incision was made in
      the mucocutaneous border of the vaginal introitus. The rectal wall was separated
      from the rectovaginal septum. The vaginal wall was divided in the middle. The
      first flap was sewn to the second and this onto the first. This intervention
      permits the contemporary correction of other pathologies frequently found in
      older women, such as cystocele and prolapse of the uterus. Twenty-two elderly
      women underwent operations using this technique; the mean follow-up period was 48
      months (range, 24-84 months). The need to assist evacuation digitally disappeared
      in all patients.

PMID- 17510740
TI  - Laparoscopic surgery for colorectal cancer: clinical practice guidelines of the
      Italian Society of Colo-Rectal Surgery.

PMID- 17510741
TI  - Long-term results after stapled haemorrhoidopexy for fourth-degree haemorrhoids:
      a prospective study with median follow-up of 6 years.
AB  - BACKGROUND: The aim of our study was to assess our early and long-term results
      after stapled haemorrhoidopexy for fourth-degree haemorrhoids. METHODS: Our study
      covers the time period from 1998 to 2002 and consists of 56 consecutive patients
      (33 men) with fourthdegree haemorrhoids who underwent stapled haemorrhoidopexy.
      RESULTS: During the postoperative period, 6 patients (10.7%) experienced pain for
      7-14 days, which was treated with oral analgesia. Ten patients (17.8%)
      experienced gas incontinence and two of them also reported soiling. The
      incontinence subsided within 3-8 weeks. Median follow-up was 72.1 months (range,
      55-86 months). Recurrence of the haemorrhoidal disease occurred in 33 patients
      (58.9%). The overall reintervention rate was 42.8%, as 24 patients required
      excisional haemorrhoidectomy by the Milligan-Morgan technique at a later stage.
      CONCLUSIONS: Stapled haemorrhoidopexy seems to be a safe, low-pain but
      ineffective technique for the treatment of fourth-degree haemorrhoids, as it is
      accompanied by high recurrence and reintervention rates in the long term.

PMID- 17510742
TI  - Open compared with closed haemorrhoidectomy: meta-analysis of randomized
      controlled trials.
AB  - AIMS: This review compares the most popular techniques in managing the wounds
      after excisional haemorrhoidectomy, which are either to lay the wounds open or to
      close them. METHODS: Randomized controlled trials were identified from the major
      electronic databases using the search terms "hemorrhoid*" and "haemorrhoid*."
      Duration of operation, pain, length of hospital stay, time off work, time for
      wound healing, patient satisfaction, continence, manometry findings and
      complications were assessed. Quantitative meta-analysis was performed as
      appropriate or possible. RESULTS: Six trials including 686 patients met the
      inclusion criteria. The median follow-up time ranged from 1.5 to 19.5 months.
      Quantitative meta-analysis showed that there was no significant difference in
      cure rates between the two techniques (relative risk, 1.4; 95% CI, 0.86 to 2.2;
      p=0.191). Open haemor-rhoidectomy was more quickly performed (weighted mean
      difference, 1.03 min; 95% CI, 0.51 to 1.54; p<0.001). Closed haemorrhoidectomy
      wounds showed faster healing (weighted mean difference, 1.2 weeks; 95% CI, 0.88
      to 1.55; p<0.001). Hospital stay, maximum pain score, total and individual
      complication rates were not significantly different. CONCLUSIONS: Apart from
      faster wound healing after closed haemorrhoidectomy, open and closed techniques
      appeared equally effective and safe. However, there were only a few studies which
      presented information in different ways, and statistical heterogeneity was high.

PMID- 17510743
TI  - Benign rectovaginal fistulas: management and results of a personal series.
AB  - BACKGROUND: Treatment of benign rectovaginal fistula has a high failure rate and
      entails difficult decisions. The purpose of this retrospective study was to
      clarify the concepts which may improve its management. METHODS: Between 1983 and
      2004, 46 consecutive women of median age 41 years were treated by the same
      surgeon. Etiology of simple fistulas was iatrogenic (n=6), obstetric (n=4) and
      septic (n=3). Complex fistulas were due to inflammatory bowel diseases (IBD)
      (n=18, 11 pouchvaginal) or were iatrogenic (n=9), actinic (n=5) or septic (n=1).
      Surgical techniques included endorectal or vaginal advancement flaps,
      fistulectomy and sphincteroplasty, vaginal/rectal closure and epiploplasty,
      restorative proctectomy and restorative proctocolectomy. In 20 patients, a
      diverting stoma was performed as a single procedure or concomitant to the
      curative attempt. RESULTS: Overall, 33 of the 39 fistulas (85%) treated for cure
      healed, including all simple fistulas and 20 complex fistulas (8 iatrogenic, 3
      actinic, 2 ulcerative colitis without restorative proctocolectomy; 5 pouch
      vaginal; 1 septic; 1 Crohn's disease) (p=0.009). The first operation for the
      fistula was curative in 20 of 39 fistulas, including 10 of 13 simple and 10 of 26
      complex fistulas (p=0.023). There was no significant age difference between cured
      and not-cured patients. CONCLUSIONS: Simple versus complex fistulas is the most
      determinant factor for healing. In IBD fistulas, ulcerative colitis shows better
      prognosis than Crohn's disease. For complex fistulas, a temporary diverting stoma
      seems necessary.

PMID- 17510745
TI  - Posterior tibial nerve stimulation for faecal incontinence after partial spinal
      injury: preliminary report.
AB  - BACKGROUND: This study evaluated the possible effects of posterior tibial nerve
      stimulation in two patients with faecal incontinence due to partial spinal cord
      injury. METHODS: Posterior tibial nerve stimulation was performed for 30 min,
      every other day for 4 weeks, and was then repeated every 2 months for three
      months. Clinical examination, anorectal physiological work-up, faecal
      incontinence severity index, and quality of life assessments were performed
      before and after the treatment. RESULTS: After posterior tibial nerve
      stimulation, patients showed improvement in rectal sensory threshold, pudendal
      nerve terminal motor latency, Wexner faecal incontinence score, faecal
      incontinence severity index, faecal incontinence quality of life scales, resting
      pressure, and maximum squeeze pressure measurements. CONCLUSIONS: Posterior
      tibial nerve stimulation can be an effective method for the treatment of faecal
      incontinence caused by partial spinal cord injury.

PMID- 17510744
TI  - Rectal bleeding and previous anticoagulant treatment in patients with colorectal
      cancer do not predict outcome.
AB  - BACKGROUND: The aim of this study was to determine whether the outcome of
      patients with colorectal cancer who presented with bleeding and a history of
      anticoagulant treatment was different from those who did not have bleeding or
      previous anticoagulant treatment. METHODS: This was a single institution,
      retrospective study of patients with colorectal cancer with and without a history
      of rectal bleeding and treatment with anticoagulants, assessed for age, gender,
      tumor site, stage, recurrence rate, and survival. RESULTS: A total of 621
      consecutive patients (309 men) with a mean age of 70 years (range, 36-94 years)
      diagnosed with colorectal cancer between 1998 and 2004 were studied. Of these,
      149 patients (24%) were referred for symptoms of rectal bleeding and 161 patients
      (26%) had been previously treated with anticoagulants. A total of 592 patients
      (95%) underwent curative or palliative surgery; endoscopic polypectomy was
      performed in 3 cases only and in 26 patients (4%) surgery was not performed due
      to advanced disease or critical illness. Patients with bleeding and a history of
      anticoagulant treatment presented commonly with stage I cancer. In addition,
      tumor stage III was less common in patients with previous anticoagulant treatment
      irrespective of presenting signs. Disease-free and overall survival rates were
      similar in all groups, irrespective of bleeding at presentation or anticoagulant
      treatment. CONCLUSIONS: Rectal bleeding and anticoagulant treatment do not affect
      the outcome of newly diagnosed patients with colorectal cancer.

PMID- 17510746
TI  - Accuracy of digital rectal examination in the estimation of height of rectal
      lesions.
AB  - BACKGROUND: To assess the accuracy of the digital rectal examination as a method
      of estimating the distance of a rectal lesion from the anal verge. METHODS: One
      hundred doctors of variable levels of experience and from different specialities
      performed digital rectal examination (DRE) on a pelvic model with two fixed
      buttons at different levels simulating lesions in the rectum. They were asked to
      estimate the distance of the lesions in centimetres from the anal verge and
      classify the lesion as mid or low rectal. RESULTS: Nearly half the doctors
      studied (45%) estimated the distance of the upper lesion accurately (7.5 cm, or
      within 1 cm of the correct distance), whereas 64% of the doctors estimated the
      distance to the lower lesion accurately (3 cm, or within 1 cm of correct
      distance). 93% of doctors classified the mid-rectal lesion correctly and 99%
      classified the lower rectal lesion correctly. CONCLUSIONS: Though less accurate
      in precisely estimating the distance of a lesion from the anal verge, DRE has
      high accuracy in classifying rectal lesions into lower and mid-rectal lesions,
      irrespective of experience and background of the clinicians. It is more accurate
      for lower rectal lesions than mid-rectal lesions.

PMID- 17510747
TI  - Routine preoperative abdominal computed tomography in colon cancer: a utility
      study.
AB  - BACKGROUND: There is no proven utility for preoperative scanning of
      intraperitoneal colonic cancer with computed tomography (CT). A prospective study
      was conducted where CT was preoperatively incorporated into the management
      algorithm to ascertain its role in patient treatment. METHODS: Thoraco-abdominal
      CT was performed in both the elective and emergency settings in an unselected
      group of 73 patients referred to a coloproctology unit established over the last
      30 months at the Queen Elizabeth Hospital, Barbados. CT and operative findings
      were compared to determine the influence that the preoperative CT had on surgical
      decision making. RESULTS: Unexpected additional pathology was found in 6.8% of
      patients. Sensitivity for the detection of visceral metastatic disease was 84.6%.
      Preoperative CT was deemed to be of clinical value in 24.7% of cases and to
      definitively alter surgical management in 13.7% of patients. These alterations in
      management included several types of multivisceral resections, the need for
      ureteric stenting or reimplantation, the utilization of stomas alone and the
      avoidance of resection in known metastatic disease. CONCLUSIONS: Preoperative CT
      of intraperitoneal colonic cancer adds important technical information to the
      conduct of the surgery and alters therapy in a selected patient group.

PMID- 17510748
TI  - Indeterminate colitis.
AB  - The term indeterminate colitis has been used to describe cases of inflammatory
      bowel disease that cannot be classified as ulcerative colitis or Crohn's disease.
      However, this term has suffered varying definitions, which in addition to
      numerous difficulties in diagnosing inflammatory bowel disease has led to much
      confusion. The term indeterminate colitis should only be used in cases where a
      colectomy has been performed and the overlapping features of Crohn's disease and
      ulcerative colitis do not allow a definitive diagnosis. Over time the majority of
      patients remain with a diagnosis of indeterminate colitis, or show symptoms
      similar to ulcerative colitis. Ileal pouch-anal anastomosis surgery can be
      performed in such patients, with outcomes of pouch failure and functional outcome
      that are similar to those in patients with ulcerative colitis but with increased
      risk of postoperative pouch complications. This review addresses the definition
      of indeterminate colitis, its pathology, natural history, and outcomes of
      restorative proctocolectomy.

PMID- 17510749
TI  - Superheating in linear polymers studied by ultrafast nanocalorimetry.
AB  - To study phase transition kinetics on submillisecond time scale a sensitive
      ultrafast nanocalorimeter was constructed. Controlled ultrafast cooling, as well
      as heating, up to 10(6) K/s was attained. The method was applied for the
      measurements of the superheating phenomenon in a set of linear polymers: iPS,
      PBT, PET, and iPP. A power law relation between the superheating and the heating
      rate holds in the heating rate range 10(-2) - 10(4) K/s. A limiting superheating
      of about 10% of the melting temperature was observed at rates above 10(4) - 10(5)
      K/s. This limit depends on annealing conditions before sample melting. The
      observed superheating limit, as well as the power law, can be accounted for the
      internal stresses near the crystalline amorphous interface in semicrystalline
      polymers induced by heating, which are related to the thermal expansion gradients
      inherent in a semicrystalline material.

PMID- 17510750
TI  - Colloidal inclusions in smectic films with spontaneous bend.
AB  - Inclusions in free-standing smectic films are simple model systems for two
      dimensional anisotropic dispersions. From theory and experiment, different
      topologies of elastic distortions of the embedding liquid crystal are known.
      Quadrupolar and different dipolar defect configurations in the vicinity of the
      inclusion are possible, and these configurations determine the type of
      interactions between the inclusions. The quadrupolar configuration is often
      energetically preferred. We show, however, that dipolar director configurations
      around inclusions can be energetically favourable over quadrupolar arrangements
      in chiral smectics, as a consequence of a spontaneous-bend term in the elastic
      energy formulation. As the inclusion size influences the selection of the
      deformation types, the corresponding spontaneous-bend constant can be estimated
      for the strong anchoring limit if the c -director fields around inclusions of
      different diameters are taken into account.

PMID- 17510751
TI  - Routine coagulation tests in newborn and young infants.
AB  - BACKGROUND: The diagnostic approach to haemostatic defects in the newborn is
      challenging and requires appropriate interpretation of coagulation tests
      according to reference values dependent on the postnatal age. METHODS: This
      investigation was designed to study the postnatal development of the human
      coagulation system in newborn infants and to develop appropriate reference ranges
      for prothrombin time (PT), activated partial thromboplastin time (APTT) and
      fibrinogen (FBG) according at the day of birth and for the following postnatal
      period (days 1, 2, 3, 4, 5, 6, from 7 to 10 and from 11 to 44). RESULTS: The mean
      FBG value was already within the adult reference range in newborns at birth, the
      mean PT value fell within the adult reference range in infants aged 4 days or
      more, whereas the mean APTT value was still higher than the upper limit of the
      adult reference range in infants aged between 11 and 20 days. The prevalence of
      infants with pathological values according to the actual adult reference ranges
      was limited for FBG (from 24 to 7%), decreased from 92 to 8% in infants aged 0
      and 11-20 days for PT, but remained elevated throughout the observational period
      for APTT (from 94 to 71%). CONCLUSIONS: The results of the present investigation
      demonstrate that the actual adult reference ranges for coagulation screening
      tests, especially PT and APTT, cannot be applied to newborns and young infants.

PMID- 17510752
TI  - Association between nitric oxide levels on myocardial injury in non-ST elevation
      acute coronary syndromes.
AB  - BACKGROUND: Impairment of the release of endothelium and platelet derived-nitric
      oxide (NO) increases thrombus formation that is rich in platelets in non-ST
      elevation acute coronary syndromes (NSTE-ACS). Since intracoronary thrombus
      formation and distal embolization increases risk of myocardial injury, we studied
      the relationship between NO levels and Tn-I in patients with NSTE-ACS. METHODS:
      Nitric oxide and Tn-I levels of 234 consecutive patients with NSTE-ACS were
      measured from venous samples at admission. The 137 patients whose Tn-I levels
      were below 0.20 ng/ml grouped as Tn-I negative and 97 patients whose Tn-I levels
      were equal to and above 0.21 ng/ml were grouped as Tn-I positive. Presence of
      visible thrombus, degree of flow in Thrombolysis in Myocardial Infarction (TIMI),
      and morphology of the lesion were evaluated with coronary angiographies. RESULTS:
      Presence of coronary thrombus, impaired TIMI flow, frequency of complex lesions,
      angina and ST-T changes were more frequent and associated with Tn-I levels in Tn
      I positive patients. NO levels were lower in patients who were Tn-I positive, had
      angina and ST-T changes. NO levels were similar between patients with simple or
      complex lesions, but lower in patients who had coronary thrombus or TIMI flow
      grade <2. There was a negative correlation between levels of Tn-I and NO (r = 
      0.87, P < 0.001). Logistic regression analysis revealed that NO levels were
      independent predictors in the differentiation of Tn-I negatives and positives (r
      = 0.527, P < 0.001). CONCLUSION: This study revealed that NO levels are
      associated with myocardial injury in patients with NSTE-ACS.

PMID- 17510753
TI  - Focus on thrombosis : Applying management guidelines in clinical practice.

PMID- 17510754
TI  - Residence time dispersion as a general measure of drug distribution kinetics:
      estimation and physiological interpretation.
AB  - PURPOSE: To evaluate distribution kinetics of drugs by the relative dispersion of
      disposition residence time and demonstrate its uses, interpretation and
      limitations. MATERIALS AND METHODS: The relative dispersion was estimated from
      drug disposition data of inulin and digoxin fitted by three-exponential
      functions, and calculated from compartmental parameters published for fentanyl
      and alfentanil. An interpretation is given in terms of a lumped organs model and
      the distributional equilibration process in a noneliminating system. RESULTS: As
      a measure of the deviation from mono-exponential disposition (one-compartment
      behavior), the relative dispersion provides information on the distribution
      kinetics of drugs, i.e., diffusion-limited distribution or slow tissue binding,
      without assuming a specific structural model. It also defines the total
      distribution clearance which has a clear physical meaning. CONCLUSION: The
      residence time dispersion is a model-independent measure that can be used to
      characterize the distribution kinetics of drugs and to reveal the influence of
      disease states. It can be estimated with high precision from drug disposition
      data.

PMID- 17510755
TI  - Determination of the relative bioavailability of salbutamol to the lungs
      following inhalation from dry powder inhaler formulations containing drug
      substance manufactured by supercritical fluids and micronization.
AB  - PURPOSE: The relative lung bioavailability of salbutamol sulfate particles
      produced using supercritical fluids (SEDS) and delivered by dry powder inhaler
      (DPI) was compared with the performance of a conventional micronized drug DPI
      using the same device design (Clickhaler, Innovata Biomed). MATERIALS AND
      METHODS: Twelve healthy volunteers and 11 mild asthmatic patients completed
      separate four-way randomised cross-over studies, assessing the relative
      bioavailability of salbutamol sulfate (urinary excretion method), formulated as
      SEDS particles (three batches) and micronized particles (Asmasal inhaler, UCB
      Pharma Ltd). Post-treatment improvements in patient lung function were assessed
      by measuring FEV(1). Physicochemical evaluation of the three SEDS batches
      revealed inter-batch differences in particle size and shape. RESULTS: There was
      no significant difference in the relative lung bioavailability of salbutamol and
      its bronchodilator response between the best performing SEDS formulation and the
      Asmasal inhaler in volunteers and patients, respectively. SEDS salbutamol sulfate
      showing wafer like morphology gave greater fine particle dose, relative lung
      bioavailability and enhanced bronchodilation compared to other SEDS batches
      containing elongated particles. CONCLUSIONS: Active Pharmaceutical Ingredient
      (API) manufactured using supercritical fluids and delivered by DPI can provide
      similar lung bioavailability and clinical effect to the conventional micronized
      commercial product. Product performance is however notably influenced by inter
      batch differences in particle characteristics.

PMID- 17510756
TI  - Implementation of extended neonatal screening and a metabolic unit in the State
      of Qatar: developing and optimizing strategies in cooperation with the Neonatal
      Screening Center in Heidelberg.
AB  - Qatar is a country in the Gulf area and member of the Gulf Cooperation Council
      states. The country is populated by original Qatari tribes that amount to about
      200,000 people and about 600,000 expatriates mainly from Arabic and Asian
      countries. Inbreeding over centuries and high rates of consanguinity in the
      Qatari population and in some groups of expatriates, in addition to large family
      sizes and rapid population growth, have contributed to a high frequency of
      autosomal recessive disorders. In December 2003 Hamad Medical Corporation in Doha
      and the University Children's Hospital of Heidelberg, Germany, started an
      extended state-wide neonatal screening programme for metabolic and endocrine
      disorders, with the laboratory situated in Heidelberg, Germany. All aspects of
      the screening process had to be adapted to the unique situation of the laboratory
      being 6000 km from the birthplace of the neonates. Within 32 months, samples of
      25,214 neonates were screened. In 28 cases an endocrine or metabolic diagnosis
      was identified (incidence 1:901, in Germany 1:1728). In particular, a variety of
      monogenic metabolic diseases were prevalent, with 19 patients detected giving an
      incidence of metabolic diseases of 1:1327 (Germany 1:2517). Each euro spent on
      the screening programme saved more than 25 euros in health and social costs. The
      programme revealed a high incidence of treatable inborn metabolic diseases in the
      population of Qatar. A reliable screening for classical homocystinuria showing a
      unique incidence of >1:3000 and for sickle cell disease has now been added.

PMID- 17510757
TI  - A trial with N-carbamylglutamate may not detect all patients with NAGS deficiency
      and neonatal onset.
AB  - N-acetylglutamate synthase (NAGS) deficiency is a rare urea cycle disorder. An
      effective treatment, N-carbamoyl-L-glutamic acid (NCGA), is now available,
      increasing the importance of identifying and treating these patients early. We
      describe a case with genetically verified NAGS deficiency and neonatal onset of
      severe hyperammonaemia. The ammonia levels increased above 1400 micromol/L. The
      patient did not respond to NCGA treatment during the first 15 h, indicating that
      a delayed response or no response cannot be used as a safe indicator for
      excluding NAGS deficiency in the acute situation. Hence, conventional treatment
      should not be delayed by a diagnostic procedure, such as a loading test.
      Furthermore, at 3 years of age this patient has normal psychomotor development,
      underlining the possibility of a favourable outcome despite markedly elevated
      ammonia levels, coma, and seizures in the neonatal period. Including NCGA early
      in the treatment of patients with hyperammonaemia may be of clinical importance.
      In order to detect patients with NAGS deficiency and neonatal onset and to
      optimize care, it is important to use the available treatment strategies to
      reduce plasma ammonia concentrations without delay. We propose the use of
      combined symptomatic treatment, i.e. glucose infusion, sodium benzoate, arginine
      or citrulline, and when indicated haemodialysis, as well as NCGA treatment in all
      neonates presenting with severe hyperammonaemia. The treatment should be
      continued until laboratory investigations are complete or indicate another
      disorder.

PMID- 17510758
TI  - D-Cycloserine and performance under different states of anxiety in healthy
      volunteers.
AB  - RATIONALE: There is interest in the development of augmentation therapy in the
      treatment of anxiety disorders. Recent publications have shown that D-cycloserine
      can benefit exposure therapy in a group of acrophobic (height phobic) subjects
      and in patients with social anxiety disorder. These studies were based on the
      animal data suggesting that drugs acting to enhance glutamate function may be
      developed to accelerate the behavioural treatment of anxiety disorders. Perhaps
      by enhancing glutamate/N-methyl-D-aspartate receptor function, learning is thus
      enhanced. This study examines the effects of D-cycloserine 50 mg on a task that
      involves learning. We manipulated anxiety levels to model the effects of high
      anxiety. OBJECTIVES: To evaluate performance and learning, we used the Manikin
      task. Two groups of 24 healthy volunteers participated in a double-blind, placebo
      controlled study. One group received the inhalation of CO(2) 7.5% to model high
      anxiety, and the second group received air to represent lower anxiety. Subjects
      received D-cycloserine 50 mg or placebo, and the Manikin task was performed
      during the gas inhalation. RESULTS: There were significant differences in the
      group inhaling air, but not CO(2), with the D-cycloserine group showing an
      increase in correct responses. This difference was apparent at several time
      blocks during the 20-min task. These findings were supported by subjective
      measures in that participants who received D-cycloserine reported that the task
      was easier. CONCLUSIONS: We have shown that at lower anxiety levels, D
      cycloserine 50 mg improved the performance of this challenging visuospatial
      cognitive task. This increase in performance was not seen when anxiety was
      higher, and D-cycloserine did not appear to increase subjective anxiety. These
      data lend support to the use of D-cycloserine and related glutamate enhancers as
      cognitive modulators and suggest that the actions of D-cycloserine are not simply
      related to increased arousal or anxiety.

PMID- 17510759
TI  - Paradoxical constitutive behavioral sensitization to amphetamine in mice lacking
      5-HT2A receptors.
AB  - RATIONALE: Although locomotor response to d-amphetamine is considered as mediated
      by an increased release of dopamine in the ventral striatum, blockade of either
      alpha1b-adrenergic or 5-HT2A receptors almost completely inhibits d-amphetamine
      induced locomotor response in mice. In agreement with this finding, mice lacking
      alpha1b-adrenergic receptors hardly respond to d-amphetamine. However, we show
      here that, paradoxically, mice lacking 5-HT2A receptors (5-HT2A-R KO) exhibit a
      twofold higher locomotor response to d-amphetamine than wild-type (WT)
      littermates. OBJECTIVES: To explore why there is a discrepancy between
      pharmacological and genetic 5-HT2A receptor blockade. MATERIALS AND METHODS:
      Locomotor response and behavioral sensitization to d-amphetamine were measured in
      presence of prazosin and/or SR46349B, alpha1b-adrenergic, and 5-HT2A receptor
      antagonists, respectively. RESULTS: Repeating amphetamine injections still
      increases 5-HT2A-R KO mice locomotor response to d-amphetamine at a level similar
      to that of sensitized WT mice. SR46349B (1 mg/kg) has, as expected, no effect in
      5-HT2A-R KO mice. One milligrams per kilogram of prazosin completely blocks d
      amphetamine-induced locomotor response in 5-HT2A-R KO naive animals but 3 mg/kg
      is necessary in sensitized 5-HT2A-R KO mice. CONCLUSIONS: Because naive 5-HT2A-R
      KO mice exhibit an increased cortical noradrenergic response to d-amphetamine,
      our data suggest that repeated d-amphetamine modifies noradrenergic transmission
      in 5-HT2A-R KO mice. Stimulation of specific 5-HT2A receptors would inhibit
      noradrenergic neurons. Dramatic decrease in SR46349B efficiency in sensitized WT
      mice indicates that a disruption of the regulating role of 5-HT2A receptors on
      noradrenergic transmission occurs during sensitization and thus represents the
      physiological basis of behavioral sensitization to d-amphetamine.

PMID- 17510760
TI  - Modification of ethanol's reinforcing effectiveness in rhesus monkeys by cocaine,
      flunitrazepam, or gamma-hydroxybutyrate.
AB  - BACKGROUND: Although ethanol is frequently used in combination with other
      psychoactive drugs, the behavioral and pharmacological reasons for this form of
      polydrug abuse have not been well described. MATERIALS AND METHODS: Rhesus
      monkeys with indwelling intravenous catheters produced intravenous injections of
      ethanol (50, 100, or 200 mg/kg/inj), flunitrazepam (0.001-0.03 mg/kg/inj),
      cocaine (0.01 or 0.03 mg/kg/inj), or combinations of ethanol and these drugs or
      gammahydroxybutyrate (GHB) (1.0 or 3.2 mg/kg/inj) by lever pressing according to
      a fixed-ratio schedule. The response requirement for each drug or drug
      combination was increased across sessions (10, 32, 100, 320, or 1,000). The
      dependent variables were rates of responding maintained by the drug or drug
      combination and the elasticity of drug demand when consumption was expressed as a
      function of price. RESULTS: Elasticity (P (max)) values for each drug varied
      among the monkeys but retained the same rank order for the monkeys, suggesting a
      fundamental difference in the animals' apparent sensitivities to the reinforcing
      effects of the drugs. Combining ethanol with the other drugs did not increase
      their reinforcing effectiveness. GHB (ineffective in previous studies) did not
      modify ethanol's reinforcing effects; demand functions for the combination of
      ethanol and flunitrazepam were slightly less elastic than for ethanol alone, but
      no different from that for flunitrazepam alone; adding ethanol to cocaine
      detracted from the reinforcing effectiveness of cocaine. CONCLUSIONS: The
      hypothesis that use of ethanol in combination with sedative and stimulant drugs
      is due to an ability of ethanol to enhance the reinforcing effects of these drugs
      is not supported.

PMID- 17510761
TI  - Application of Taenia saginata metacestodes as an alternative antigen for the
      serological diagnosis of human neurocysticercosis.
AB  - Serological tests are an important tool for the diagnosis of neurocysticercosis
      (NCC), the disease caused by Taenia solium metacestodes. The aim of the present
      research was to test the application of Taenia saginata metacestodes as an
      alternative antigen for use in the immunofluorescence antibody test (IFAT),
      enzyme-linked immunosorbent assay (ELISA), and Western blotting (WB) tests
      compared with the metacestodes antigen of T. solium in serum samples. The samples
      were obtained from 130 individuals: 20 from patients with definitive NCC, Group
      1; 18 from individuals infected by Taenia sp., Group 2; 40 from individuals
      infected by various parasites, Group 3; and 40 from healthy individuals, Group 4.
      The sensitivity of IFAT, ELISA, and WB using antigen obtained from T. solium
      applied to the patients of Group 1 yielded results of 85, 95, and 95%,
      respectively, for the three tests. When the tests were conducted using T.
      saginata metacestodes, results were 75, 80, and 85%, respectively. The
      specificity of IFAT, ELISA, and WB using antigen obtained from T. solium yielded
      results of 94.9, 88.8, and 93.9%. When the tests were conducted using T. saginata
      metacestodes, results were 95.9, 88.8, and 93.6%, respectively. No statistical
      differences for sensitivity or specificity among the antigens were found. In
      conclusion, the results indicated that T. saginata metacestodes can be used as an
      alternative antigen for NCC diagnosis.

PMID- 17510762
TI  - Mechanism of lysophosphatidylcholine-induced lysosome destabilization.
AB  - Lysosomal destabilization is critical for the organelle and living cells.
      Phospholipase A(2 )(PLA(2)) was shown to be able to destabilize lysosomes under
      some conditions. By what mechanism the enzyme affects lysosomal stability is not
      fully studied. In this study, we investigated the effects of
      lysophosphatidylcholine (lysoPC), a PLA(2)-produced lipid metabolite, on
      lysosomal ion permeability, osmotic sensitivity and stability. By measuring
      lysosomal beta-hexosaminidase free activity, membrane potential, proton leakage
      and their enzyme latency loss in hypotonic sucrose medium, we established that
      lysoPC could increase the lysosomal permeability to both potassium ions and
      protons and enhance lysosomal osmotic sensitivity. These changes in lysosomal
      membrane properties promoted entry of potassium ions into lysosomes via K(+)/H(+)
      exchange. The resultant osmotic imbalance across the membranes led to losses of
      lysosomal integrity. The enhancement of lysosomal osmotic sensitivity caused the
      lysosomes to become more liable to destabilization in osmotic shock. These
      results suggest that lysoPC may play a key role in PLA(2)-induced lysosomal
      destabilization.

PMID- 17510763
TI  - Forest floor bacterial community composition and catabolic profiles in relation
      to landscape features in Quebec's southern boreal forest.
AB  - Bacterial communities mediate many of the processes in boreal forest floors that
      determine the functioning of these ecosystems, yet it remains uncertain whether
      the composition of these communities is distributed nonrandomly across the
      landscape. In a study performed in the southern boreal mixed wood forest of
      Quebec, Canada, we tested the hypothesis that stand type (spruce/fir, aspen,
      paper birch), stand age (57, 78-85, and 131 years old), and geologic parent
      material (clay and till) were correlated with forest floor bacterial community
      composition. Forest floors in 54 independent forest stands were sampled to
      comprise a full factorial array of the three predictor variables. Bacterial
      community structure was examined by terminal restriction fragment (T-RF) length
      polymorphism analysis of genes encoding for 16S rRNA. Distance-based redundancy
      analysis of T-RF assemblages revealed that each predictor variable, as well as
      their interaction terms, had a significant effect on bacterial community
      composition, geologic parent material being the most discriminating factor. A
      survey of the 15 T-RFs with the highest percentage fit on the first two
      ordination axes describing the main effects indicated that each landscape feature
      correlated to a distinct group of bacteria. A survey of the most discriminant T
      RFs describing the effect of stand type within each combination of stand age and
      geologic parent material indicated a strong dependency of several T-RFs on
      geologic parent material. Given the possible link between bacterial community
      composition and forest floor functioning, we also assessed the effects of the
      same three landscape features on community-level catabolic profiles (CLCP) of the
      extractable forest floor microbiota. Geologic parent material and stand type had
      significant effects on CLCPs. On clay plots, the effects of landscape features on
      T-RF patterns were highly consistent with their effects on CLCPs. In light of our
      results, we suggest that future research examine whether bacterial community
      composition or CLCPs can be used to detect latent environmental changes across
      landscape units.

PMID- 17510764
TI  - Constrictive pericarditis at abdominal CT: a commonly overlooked diagnosis.
AB  - BACKGROUND: The purpose of this study was to evaluate findings at abdominal
      computed tomography (CT) in patients with proven constrictive pericarditis.
      METHODS: The medical records of 25 patients with surgically proven constrictive
      pericarditis and abdominal CT examinations within 30 days of operation were
      reviewed. Clinical symptoms, laboratory findings and prospective CT findings were
      collated. The CT examinations were also retrospectively reviewed in an unblinded
      fashion. RESULTS: Direct CT findings of constrictive pericarditis with an
      abnormal pericardium were present in 23/25 patients. Only 9 of 25 (36%) patients
      were detected prospectively. Findings on retrospective review included
      pericardial calcification (10/25, 40%) or thickening (13/25, 52%), dilated IVC
      (20/25), dilated hepatic veins (14/25), ascites (14/25), mesenteric soft tissue
      stranding (12/25), mottled enhancement of the hepatic parenchyma (8/25), and
      cirrhosis (6/25). Anemia was present in (17/25), and an elevated AST levels
      occurred in 48% (12/25) of patients. The most common abdominal symptoms were pain
      (4/12), diarrhea (4/12), distention (3/12), and bloating (1/12). CONCLUSIONS:
      Constrictive pericarditis can present with vague abdominal symptoms. Anemia and
      elevated liver function tests are common laboratory abnormalities. Indirect CT
      findings of dilated IVC and/or hepatic veins, ascites, or cirrhosis should prompt
      inspection of the pericardium. In the majority of cases an abnormal pericardium
      could be identified (thickened, calcified or both).

PMID- 17510766
TI  - Pain after open preperitoneal repair versus Lichtenstein repair: a randomized
      trial.
AB  - BACKGROUND: The open preperitoneal approach in inguinal hernia repair might have
      the benefit of a mesh in the preferred space without the disadvantages of an
      endoscopic procedure. METHODS: A total of 172 patients with primary inguinal
      hernia were randomized to undergo the open preperitoneal Kugel or the standard
      open anterior Lichtenstein procedure in a teaching hospital. The main outcome
      measures were operating variables, visual analog scale (VAS) pain scores, and
      consumed analgesics during the first 2 weeks postoperatively and at 3 months,
      neurological examination, and complications. RESULTS: In the Lichtenstein group
      the operation took longer (54 min versus 41 min; p < .001). There were no
      clinically important differences in VAS pain score or number of analgesics during
      the first 2 weeks postoperatively. In the Kugel group the mean VAS pain score at
      3 months was less (0.3 versus 0.9; p = .002), as was the proportion of patients
      reporting pain (21 versus 40%; p = .007). Pain was merely described as
      neuropathic, especially in the Lichtenstein group. With the anterior repair
      significantly more nerves were encountered, numbness reported, and cutaneous
      sensory changes found with neurological examination (all p < .001). CONCLUSIONS:
      For those surgeons preferring an open approach, the Kugel procedure is a feasible
      alternative for the standard Lichtenstein procedure and is associated with less
      chronic pain at three months. Most likely the neuropathic pain and numbness with
      the Lichtenstein technique are results of more nerves at risk with the anterior
      approach.

PMID- 17510767
TI  - Prognostic factors affecting survival and recurrence of patients with pT1 and pT2
      colorectal cancer.
AB  - BACKGROUND: Data on the prognostic factors of survival and recurrence in patients
      with colorectal cancers confined to the bowel wall (T1 and T2) are limited. The
      aim of the present study was to determine factors that might predict the survival
      and recurrence of patients who had T1 and T2 colorectal cancers. PATIENTS AND
      METHODS: All patients with T1 or T2 colorectal cancers who underwent resection in
      the Department of Surgery, University of Hong Kong Medical Centre, from 1996 to
      2004 were included. Analysis was made from the prospectively collected database.
      Predictive factors for lymph node metastasis and prognostic factors were
      analyzed. RESULTS: A total of 265 patients (144 men) with the median age of 71
      years (range: 33-93 years) were included. Seventy-two patients had T1 cancers
      (rectal cancer n = 44; colon cancer n = 28; p = 0.89) and 193 patients suffered
      from T2 cancer (rectal n = 120; colon cancer n = 73). The overall incidence of
      lymph node metastasis was 12.7% (5.6% for T1 cancer and 14.5% for T2 cancer; p =
      0.021). The presence of lymphovascular permeation was the only independent factor
      associated with a higher incidence of lymph node metastasis on multivariate
      analysis (odds ratio: 1.48, 95% CI: 1.44-13.47, p = 0.009). There were no
      significant differences in disease-free 5-year survival (T1 = 84.6%; T2 = 81.1%)
      and 5-year cancer-specific survival in patients with T1 and T2 tumors (T1 =
      90.2%; T2 = 90.6%). Patients with lymph node metastasis had a significantly
      shorter disease-free 5-year survival (p < 0.001) and 5-year cancer-specific
      survival (p = 0.002) when compared with those having a negative lymph node
      status. Cox proportional hazards model analysis showed that lymph node status was
      the only significant independent factor predicting cancer-specific survival
      (hazard ratio: 3.52, 95% CI: 1.60-7.71, p = 0.002) and disease-free survival
      (hazard ratio: 3.42, 95% CI: 1.75-6.69, p < 0.001). CONCLUSIONS: Presence of
      lymphovascular permeation would have a significant higher chance of lymph node
      metastasis. Positive lymph node status was predictive of poorer survival in
      patients with T1 or T2 colorectal cancers. For those cancers with positive
      lymphovascular permeation, radical surgery is recommended.

PMID- 17510768
TI  - Clinical observations from a breast cancer registry in Asian women.
AB  - BACKGROUND: The incidence of breast cancer in Singapore, reflecting cancer trends
      of developed nations, is rising rapidly. It is the most common cancer in
      Singaporean women. Given the significant problem that breast cancer poses, this
      study reports the clinical-pathologic features of 1,165 women with invasive
      breast cancer managed at a university teaching hospital in Singapore. METHODS:
      All patients who were diagnosed, treated, and followed-up at this institution
      between 1990 and 2002 were analyzed. Data were obtained from the National
      University Hospital Breast Cancer Registry. RESULTS: Of our patients, 82% were
      ethnic Chinese. The median age of presentation was 49 years, and 24.5% of our
      patients presented with stage I disease. In addition, 51% of premenopausal and
      60% of postmenopausal patients stained positive for estrogen receptor. Mastectomy
      was the most common surgical therapy, and about 90% of patients received adjuvant
      therapy. At a median follow-up of 81 months, the median 5-year survival was as
      follows: stage I, 97%, stage II, 78%, stage III, 52%, and stage IV, 13%.
      CONCLUSIONS: This study supports what has been observed among breast cancer
      patients in this region and reflects a profile of breast cancer that differs from
      that seen in the West: patients present at a younger age, with more advanced
      stage and fewer estrogen-positive tumors. Most women in our series received
      systemic adjuvant therapy, and the 5-year overall survival rates are equivalent
      to published results from the West. The unique features of the disease in women
      in Singapore are important to recognize, as they may influence future prevention
      and management strategies for Asian women with breast cancer.

PMID- 17510769
TI  - The impact of lymph node metastases on survival in extremity soft tissue
      sarcomas.
AB  - BACKGROUND: The impact of lymph node metastases on survival in extremity soft
      tissue sarcomas has been studied for a long time with controversial results. The
      purpose of this study was to compare survival of patients with initial lymph node
      metastases with those having lymph node or distant metastases or both after
      initial curative surgery. METHODS: Patients treated between 1995 and 2000 for
      extremity soft tissue sarcoma were retrospectively studied in four groups: those
      with metastatic regional lymph nodes at the time of diagnosis, those with only
      regional lymph node recurrences, those with only distant metastatic relapses, and
      those with both regional lymph node recurrences and distant metastatic relapses,
      all of the last three groups after initial curative surgery. The impact of timing
      of lymph node metastases on disease-free and overall survival was evaluated.
      RESULTS: A total of 110 patients (73 men) with a median age of 45 years were
      eligible for the study. Three-year disease-free survival was significantly longer
      in patients with initial regional lymph node metastases than in patients with
      only lymph node recurrences after curative surgery (p = 0.04) and patients with
      initial (p = 0.0002) and recurrent (p = 0.0004) regional lymph node metastases
      had longer disease-free survival than patients with distant metastases. Overall
      survival difference between patients with initial regional lymph node metastases
      and patients with only lymph node recurrences after curative surgery was
      significant at 5 years (p = 0.01). CONCLUSIONS: It is logical to separate
      patients with initial lymph node metastases from those with distant metastases in
      staging and to treat patients with initial lymph node metastases with radical
      surgical interventions if complete tumor resection seems feasible.

PMID- 17510770
TI  - Fetal tracheal occlusion for the treatment of congenital diaphragmatic hernia.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) continues to be associated with
      significant mortality and morbidity rates despite advances in neonatal care.
      Fetal intervention for CDH has been studied for 25 years. After initial
      difficulties encountered with open fetal repair, attention has turned to tracheal
      occlusion (TO) as a method to correct pulmonary hypoplasia before birth. This
      article reviews our contribution to this field of research and outlines the
      current status of this treatment modality. MATERIALS AND METHODS: Using the fetal
      lamb model, we have studied the effects of fetal TO on tracheal fluid pressure,
      lung growth and type II pneumocyte maturation, and surfactant production. We
      developed a minimally invasive and reversible technique of TO, using a detachable
      balloon placed using single-port tracheoscopy. We examined differential lung
      growth, structural maturation, pulmonary artery remodeling, and lung function
      during an 8-h resuscitation period in lambs, comparing normal controls, lambs
      with a surgically created CDH, those with CDH+TO, and those with CDH+TO and
      release of TO 1 week before delivery. We also studied the potential benefits of
      maternal betamethasone administration and the administration of surfactant at
      birth. Using a neonatal piglet model, we examined the effect of postnatal
      pulmonary distension with perfluorocarbon on lung growth. More recently, we
      turned to the rat nitrofen-induced CDH model to study the effects of TO on
      bronchial branching and some molecular markers of lung growth (Shh and LGL1).
      CONCLUSIONS: Fetal TO is being used to treat human CDH, but its application
      remains limited by the absence of reliable and widely reproducible prenatal
      prognostic criteria. A better understanding of the molecular events guiding the
      lung growth seen with TO may help to refine its use in humans.

PMID- 17510771
TI  - Conflicts in decision-making for breast cancer surgery.
AB  - BACKGROUND: Little is known about the interaction among surgeons, patients, and
      other physicians in selecting breast cancer surgery. METHODS: We contacted
      attending surgeons (n = 456) of a population-based sample of 2645 breast cancer
      patients diagnosed in Detroit and Los Angeles from December 2001 to January 2003.
      Eighty percent completed a written survey with clinical scenarios. RESULTS: The
      mean surgeon age was 50 years, 50% practiced in a community hospital, and breast
      cancer averaged 31% of practice volume. The mean number of years in practice was
      17.2. Female surgeons made up 14.4% of the sample and 35% of the high-volume
      surgeons. Conflict with patients and other providers was reported by 58% and 32%
      of surgeons, respectively. When the patient preferred mastectomy and the surgeon
      favored BCS, conflict was reported by 49.9% of surgeons. Compared with low-volume
      surgeons, high-volume surgeons were significantly more likely to report conflict
      in this scenario (44% vs 62%; P = .047). When another provider preferred
      mastectomy and the respondent surgeon favored BCS, conflict was reported by 34%
      of surgeons and was more common for high-volume surgeons (P < .001). In a
      logistic regression model, surgeon volume and practice setting were strongly
      associated with conflict in this scenario. CONCLUSION: High-volume surgeons and
      those in cancer centers more frequently endorse current clinical guidelines that
      favor BCS over mastectomy, resulting in greater conflict with patients. These
      findings support patient reports that patient choice is a key factor in continued
      mastectomy use.

PMID- 17510772
TI  - Prognostic value of circulating tumor markers in patients with pseudomyxoma
      peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy.
AB  - BACKGROUND: Encouraging results have been recently reported in selected patients
      affected by pseudomyxoma peritonei (PMP) treated with cytoreductive surgery (CRS)
      and hyperthermic intraperitoneal chemotherapy (HIPEC). The selection factors
      predicting clinical outcome are still a matter of clinical investigation. We
      assessed the prognostic reliability of serum tumor markers in a large series of
      patients with PMP undergoing CRS and HIPEC. METHODS: Sixty-two patients with PMP
      were operated on at a single institution with the intent of performing adequate
      CRS (residual tumor nodules </=2.5mm) and HIPEC. Baseline and serial marker
      measurements were prospectively collected and tested by multivariate analysis
      with respect to adequate cytoreduction, overall (OS) and progression-free (PFS)
      survival, along with the following variables: age, sex, performance status, prior
      surgical score, histological subtype, prior systemic chemotherapy, disease
      extent, completeness of cytoreduction. RESULTS: Baseline diagnostic sensitivity
      was 72.6% for CEA, 58.1% for CA19.9, 58.7% for CA125, 36.1% for CA15.3. Fifty
      three patients underwent adequate CRS and HIPEC; gross residual tumor was left
      after surgery in nine. Adequate CRS was performed in 19/27 patients with elevated
      and in 19/19 with normal baseline CA125 (P = .0140). The other markers were
      unable to predict the completeness of CRS by univariate analysis. Baseline
      elevated CA19.9 was an independent predictor of reduced PFS; inadequate CRS and
      aggressive histology were independent prognostic factors for both reduced OS and
      PFS. CONCLUSION: Normal CA125 correlated to the likelihood to achieve adequate
      CRS, which is a significant prognostic factor for PMP. Increased baseline CA19.9
      was an independent predictor of worse PFS after CRS and HIPEC.

PMID- 17510773
TI  - Decreasing pancreatic leak after distal pancreatectomy: saline-coupled
      radiofrequency ablation in a porcine model.
AB  - Despite marked improvements in pancreatic surgery, the high incidence and
      morbidity of pancreatic leak after resection has remained unchanged. The
      objective of this study was to evaluate the role of saline-coupled radiofrequency
      ablation (TissueLink) as an alternative to traditional methods of stump closure
      in an animal model of distal pancreatectomy. Forty swine were randomized after
      pancreatic transection and remnant stump was either oversewn in a traditional
      fashion (control) or treated with the device alone (TissueLink). Animals were
      killed and necropsied at 3 or 5 weeks postoperatively. Primary endpoints were the
      development of a pancreatic fistula defined as dye extravasation from the remnant
      duct, presence of undrained amylase-rich fluid collections/abscess, and greater
      than threefold drain/serum amylase after the third postoperative day. The
      incidence of pancreatic leak in the TissueLink group was 5.5 vs 42% in the
      control group (p = 0.01). There were no differences in operative time or other
      clinical parameters measured. Histologic analysis of the remnant pancreatic
      stumps confirmed our results. These data support our hypothesis that saline
      coupled radiofrequency ablation leads to obliteration of ducts with a resultant
      decrease in pancreatic leak and subsequent complications. This technology may
      play a substantial role in preventing this dreaded complication in the clinical
      setting.

PMID- 17510774
TI  - Pancreatic VIPomas: subject review and one institutional experience.
AB  - VIPomas are rare pancreatic endocrine tumors associated with a well-defined
      clinical syndrome characterized by watery diarrhea, hypokalemia, and metabolic
      acidosis. The objective of this study was to review a single institution's
      experience with VIPomas, as well as to review the English literature. A
      retrospective review of the Johns Hopkins pancreatic database revealed four cases
      of VIPoma, with three patients being male. All patients presented with watery
      diarrhea, hypokalemia, hypercalcemia, and acidosis. All patients had no family
      history of multiple endocrine neoplasia. Computed tomography revealed the primary
      pancreatic tumor in all patients, with three tumors located in the tail of the
      pancreas. One tumor involved the entire pancreas. Computed tomography and/or
      octreotide radionuclide scans identified hepatic metastasis in three patients.
      Mean serum vasoactive intestinal polypeptide levels were 683 pg/ml (range 293 to
      1,500 pg/ml). All patients underwent resection of the pancreatic primary tumor.
      Two patients also had simultaneous liver resections. All patients had evidence of
      malignancy as defined by the presence of metastatic lymph nodes and/or hepatic
      metastases. Two patients had complete resolution of symptoms after surgical
      resection. One patient required radioablation of liver metastases and adjuvant
      octreotide therapy for control of symptoms. One patient died of progressive
      metastatic disease 96 months after surgery, whereas the other three remain alive.
      Extended, meaningful survival can be achieved for VIPoma patients, combining an
      aggressive surgical approach with additional strategies for treatment of
      unresected disease.

PMID- 17510775
TI  - Genetic variability of group A and B human respiratory syncytial viruses isolated
      from 3 provinces in China.
AB  - The genetic variability of HRSV in China was studied using nucleotide sequencing
      of the hypervariable C-terminal region of the G protein gene and phylogenetic
      analysis on 80 isolates obtained from three children's hospitals over a period of
      three epidemic seasons, 1990/1991, 2000/2001, and 2003/2004. The results showed
      that 76/80 of these isolates belonged to group A and 4/80 belonged to group B.
      Phylogenetic analysis revealed that most of the group A isolates were genotype
      GA2 (74/76 isolates), and the other two isolates were GA3 and GA5. All group B
      isolates clustered into genotype GB3. There was substantial variation among the
      GA2 isolates, with nucleotide sequence and amino acid homologies ranging from
      88.1-100% and 78.4-100%, respectively, in the hypervariable C-terminal region of
      the G protein gene. One group B virus, HRSV/Beijing/B/04/11, contained a 60
      nucleotide duplication in the C-terminal region of the G protein, which was
      similar to what has been reported previously for isolates in several countries.
      This is the first report on the genetic diversity of human respiratory syncytial
      virus isolated during epidemic periods from children in China. These data
      provided a preliminary evaluation of patterns of circulation and the genetic
      diversity of isolates associated with HRSV epidemics within China.

PMID- 17510776
TI  - Depression during pregnancy and the postpartum period in adolescent and adult
      Portuguese mothers.
AB  - OBJECTIVE: To study prevalence as well as risk factors for pregnancy and
      postpartum depression in a sample of adolescent and adult Portuguese mothers.
      METHODS: The Edinburgh Postnatal Depression Scale (EPDS) was administered to 108
      (54 adult and 54 adolescent) Portuguese women at 24-36 weeks of pregnancy and at
      2-3 months postpartum. RESULTS: Rates for EPDS > 12 are high during the 3(rd)
      trimester of pregnancy (18.5%) and at 2-3 months postpartum (17.6%), and not
      significantly different between these two periods; more than 1/4 of the sample
      (27.8%) had an EPDS > 12 before or after delivery. Adolescent mothers presented
      more depressive symptoms as well as more EPDS > 12 than adult mothers, both in
      pregnancy (25.9% versus 11.1%) and at 2-3 months postpartum (25.9% versus 9.3%);
      moreover, when considering other socio-demographics, adolescent mothers were
      still at risk for depressive symptoms during pregnancy as well as for postpartum
      depression. Women depressed in pregnancy, and ones who are under 18 years old and
      who live with the partner, were at risk for postpartum EPDS > 12. CONCLUSION:
      Adolescent mothers seem particularly at risk for depression during pregnancy and
      the postpartum period, therefore, just like the women who are depressed during
      pregnancy, they should be better targeted in preventive and intervention
      measures.

PMID- 17510777
TI  - Identification and biosynthetic studies of the hydrocarbon sex pheromone in
      Utetheisa ornatrix.
AB  - The type II class of sex pheromones found in moths is composed of polyene
      hydrocarbons and their epoxides. Analysis of Utetheisa ornatrix females by gas
      chromatography-mass spectrometry and measurement of responses of male moths by
      coupled gas chromatography-electroantennogram detection confirmed the presence of
      large amounts of (Z,Z,Z)-1,3,6,9-heneicosatetraene (1,3,6,9-21:Hy) and smaller
      amounts of (Z,Z, Z)-3,6,9-heneicosatriene (3,6,9-21:Hy). Both compounds were
      detected in pheromone glands of newly emerged adults, with low amounts found in
      the late pupal stage, indicating that sex pheromone biosynthesis started in the
      late pupal stage. In our population of females (several hundred sampled),
      approximately 90% produced the tetraene, 1,3,6,9-21:Hy, as the major component,
      while the other 10% produced only a large amount (1500-2000 ng) of 3,6,9-21:Hy,
      with no detectable amount of the tetraene. This result could indicate that two
      distinct populations are present in our original collection site in Florida.
      Decapitated female moths accumulated 3,6,9-21:Hy and 1,3,6,9-21:Hy compared to
      the same age normal females, indicating that female moths continuously produce
      pheromone. A pheromone biosynthesis activating neuropeptide (PBAN)-like
      neuropeptide did not affect sex pheromone production as indicated by injection of
      synthetic PBAN and decapitation of U. ornatrix female adults. When the labeled
      precursor, D4-9,12,15-18:acid, was injected into the early pupal stage, the most
      abundantly labeled hydrocarbons were 3,6,9-21:Hy and 1,3,6,9-21:Hy in the female
      adults. This result indicated that 3,6,9-21:Hy could be biosynthesized from
      linolenic acid through chain elongation and decarboxylation. To determine how
      1,3,6,9-21:Hy is produced, D4-3,6,9-21:Hy was injected into pupae and monitored
      for incorporation of label. No label was incorporated into 1,3,6,9-21:Hy,
      although a large amount of triene, 3,6,9-21 :Hy, was recovered in the pheromone
      gland. This indicates that U. ornatrix females do not use 3,6,9-21:Hy to produce
      1,3,6,9-21:Hy, and the terminal double bond is introduced earlier in the
      biosynthetic pathway.

PMID- 17510778
TI  - Metal-enhanced singlet oxygen generation: a consequence of plasmon enhanced
      triplet yields.
AB  - In this Rapid Communication, we report the first observation of Metal-Enhanced
      singlet oxygen generation (ME(1)O(2)). Rose Bengal in close proximity to Silver
      Island Films (SiFs) can generate more singlet oxygen, a three-fold increase
      observed, as compared to an identical glass control sample but containing no
      silver. The enhanced absorption of the photo-sensitizer, due to coupling to
      silver surface plasmons, facilitates enhanced singlet oxygen generation. The
      singlet oxygen yield can potentially be adjusted by modifying the choice of MEF
      (Metal-Enhanced Fluorescence) & MEP (Metal Enhance Phosphorescence) parameters,
      such as distance dependence for plasmon coupling and wavelength emission of the
      coupling fluorophore. This is a most helpful observation in understanding the
      interactions between plasmons and lumophores, and this approach may well be of
      significance for singlet oxygen based clinical therapy.

PMID- 17510779
TI  - Comparative investigation on nanocrystal structure and luminescence properties of
      gadolinium molybdates codoped with Er(3+)/Yb (3+).
AB  - This paper reports on the comparative investigation of nanocrystal structure and
      luminescence properties of Er(3+)/Yb(3+)-codoped gadolinium molybdate
      nanocrystals Gd(2)(MoO(4))(3) and Gd(2)MoO(6) synthesized by the Pechini method
      with citric acid and ethylene glycol. Their crystallization, structure
      transformation, and morphologies have been investigated by X-ray diffraction,
      thermogravimetric/differential scanning calorimetry, and transmission electron
      microscopy. It is noticed that Er(3+)/Yb(3+)-codoped monoclinic Gd(2)(MoO(4))(3)
      nanocrystals have shown an intense upconversion through a sintering of the
      organic complex precursor at 600 degrees C. Furthermore, it transforms to
      orthorhombic Gd(2)(MoO(4))(3) when the precursor is sintered at 900 degrees C. In
      counterpart of monoclinic Gd(2)MoO(6), however, the monoclinic structure remains
      unchanged when the precursor is sintered at a temperature ranging from 600
      degrees C to 900 degrees C. Intense visible emissions of Er(3+) attributed to the
      transitions of (2)H(11/2), (4)S(3/2)-(4)I(15/2) at 520 and 550 nm, and (4)F(9/2)
      (4)I(15/2) at 650 nm have been observed upon an excitation with a UV source and a
      980 nm laser diode, and the involved mechanisms have been explained. It is quite
      interesting to observe obvious differences both in the excitation and the
      upconversion emission spectra of Er(3+)/Yb(3+)-codoped Gd(2)(MoO(4))(3)
      respectively with monoclinic and orthorhombic structure. The quadratic dependence
      of fluorescence on excitation laser power has confirmed that two-photons
      contribute to upconversion of the green-red emissions.

PMID- 17510780
TI  - Purification and characterization of a bacterial phytase whose properties make it
      exceptionally useful as a feed supplement.
AB  - A periplasmatic phytase from a bacterium isolated from Malaysian waste water was
      purified about 173-fold to apparent homogeneity with a recovery of 10% referred
      to the phytase activity in the crude extract. It behaved as a monomeric protein
      with a molecular mass of about 42 kDa. The purified enzyme exhibited a single pH
      optimum at 4.5. Optimum temperature for the degradation of phytate was 65 degrees
      C. The kinetic parameters for the hydrolysis of sodium phytate were determined to
      be KM=0.15 mmol/l and kcat=1164 s(-1) at pH 4.5 and 37 degrees C. The purified
      enzyme was shown to be highly specific. Among the phosphorylated compounds
      tested, phytate was the only one which was significantly hydrolysed. Some
      properties such as considerable activity below pH 3.0, thermal stability and
      resistance to pepsin make the enzyme attractive for an application as a feed
      supplement.

PMID- 17510782
TI  - The neuronal dynamics underlying cognitive flexibility in set shifting tasks.
AB  - The ability to switch attention from one aspect of an object to another or in
      other words to switch the "attentional set" as investigated in tasks like the
      "Wisconsin Card Sorting Test" is commonly referred to as cognitive flexibility.
      In this work we present a biophysically detailed neurodynamical model which
      illustrates the neuronal base of the processes related to this cognitive
      flexibility. For this purpose we conducted behavioral experiments which allow the
      combined evaluation of different aspects of set shifting tasks: uninstructed set
      shifts as investigated in Wisconsin-like tasks, effects of stimulus congruency as
      investigated in Stroop-like tasks and the contribution of working memory as
      investigated in "Delayed-Match-to-Sample" tasks. The work describes how general
      experimental findings are usable to design the architecture of a biophysical
      detailed though minimalistic model with a high orientation on neurobiological
      findings and how, in turn, the simulations support experimental investigations.
      The resulting model is able to account for experimental and individual response
      times and error rates and enables the switch of attention as a system inherent
      model feature: The switching process suggested by the model is based on the
      memorization of the visual stimuli and does not require any synaptic learning.
      The operation of the model thus demonstrates with at least a high probability the
      neuronal dynamics underlying a key component of human behavior: the ability to
      adapt behavior according to context requirements--cognitive flexibility.

PMID- 17510781
TI  - Biochemical characterization of a S-glutathionylated carbonic anhydrase isolated
      from gills of the Antarctic icefish Chionodraco hamatus.
AB  - Gill cytoplasmic carbonic anhydrase of the haemoglobinless Antarctic icefish
      Chionodraco hamatus (Ice-CA) was directly sequenced and consists in 259 residues
      with an acetylated N-terminus. The molecular mass, deduced from the sequence, was
      28.45 kDa, while mass spectrometry analysis of the native protein gave higher
      values. Treatment with dithiothreitol abolished this difference, indicating
      possible post-translational modifications. Isoelectric focusing analysis of Ice
      CA suggested S-thiolation, which was identified as S-glutathionylation by
      immunostaining. Deglutathionylated Ice-CA maintained the anhydrase activity but
      showed higher susceptibility to hydrogen peroxide, suggesting that glutathione
      binding to Cys residues may have a role in the defence against oxidative damage.
      Ice-CA is characterized by lower thermal stability, higher activity and lower
      activation energy than its homologue gill CA of the temperate European eel,
      confirming the adaptation of the catalytic capacity to low temperatures.
      Alignment of Ice-CA with homologous enzymes from other fish shows high identity;
      the enzyme is grouped with a previously described fish CA monophyletic clade
      although Ice-CA shows several characteristics that can increase protein-solvent
      interaction and structural flexibility.

PMID- 17510783
TI  - High-resolution analysis of CpG methylation and in vivo protein-DNA interactions
      at the alternative Epstein-Barr virus latency promoters Qp and Cp in the
      nasopharyngeal carcinoma cell line C666-1.
AB  - Transcripts for the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNAs) are
      initiated at alternative promoters (Wp, Cp, for EBNA 1-6 transcripts and Qp, for
      EBNA 1 transcripts only) located in the BamHI W, C or Q fragment of the viral
      genome. To understand the host-cell dependent expression of EBNAs in EBV
      associated tumors (lymphomas and carcinomas) and in vitro transformed cell lines,
      it is necessary to analyse the regulatory mechanisms governing the activity of
      the alternative promoters of EBNA transcripts. Such studies focused mainly on
      lymphoid cell lines carrying latent EBV genomes, due to the lack of EBV
      associated carcinoma cell lines maintaining latent EBV genomes during cultivation
      in tissue culture. We took advantage of the unique nasopharyngeal carcinoma cell
      line, C666-1, harboring EBV genomes, and undertook a detailed analysis of CpG
      methylation patterns and in vivo protein-DNA interactions at the latency
      promoters Qp and Cp. We found that the active, unmethylated Qp was marked with
      strong footprints of cellular transcription factors and the viral protein EBNA 1.
      In contrast, we could not detect binding of relevant transcription factors to the
      methylated, silent Cp. We concluded that the epigenetic marks at Qp and Cp in
      C666-1 cells of epithelial origin resemble those of group I Burkitt's lymphoma
      cell lines.

PMID- 17510784
TI  - Hydrophilicity dependent budding and secretion of chimeric HIV Gag-V3 virus-like
      particles.
AB  - Virus-like particles (VLPs) of numerous viruses have been considered as possible
      candidates for vaccine development. We have constructed HIV chimeric genes by
      coupling the gag gene of HIV-2 with the V3 domain of the gp120 gene of either HIV
      1 or HIV-2 and expressed the chimeric genes in SF21 cells using the recombinant
      baculovirus expression system. Although the level of expression of the chimeric
      HIV-2 gag gene with the V3 domain of either HIV-1 gp120 (gagC-1V3) or HIV-2 gp120
      (gagC-2V3) was high, the VLP assembly and extracellular release of GagC-1V3 was
      very poor. In contrast, GagC-2V3 chimeric proteins formed VLPs and released
      efficiently. We have constructed substitution mutants to investigate the effects
      of the hydrophobic region of the V3 domain of HIV-1 Gp120 (1V3) in VLP assembly
      and release. The substitution mutant analyses revealed that in replacing the
      hydrophobic region of the 1V3 in GagC-1V3 with the hydrophilic sequence of the V3
      domain of HIV-2 Gp120 (2V3) enhanced the extracellular VLP. We demonstrate here
      that disruption of the hydrophobic character of the C-terminus of the chimeric
      protein improves assembly and release of the VLPs. Our results suggest that the
      poor GagC-1V3 VLP release was attributed to the hydrophobic region in the V3
      sequence of the chimeric protein, and that not only the N-terminal myristylation
      and positively charged domain of the Gag protein functioned as a targeting signal
      to direct membrane binding, but also that the C-terminal hydrophobic region
      affected release of chimeric VLPs.

PMID- 17510785
TI  - Of bugs and boojums: female orgasm as a facultative adaptation.

PMID- 17510787
TI  - HIV and housing assistance in four U.S. cities: variations in local experience.
AB  - This paper provides an account of how young, HIV-positive women manage their
      lives on limited budgets in four United States cities: New York City, New
      Orleans, Miami, and Chicago. The study findings elucidate city-to-city
      variability in housing assistance, and how this manifests in locality specific
      differences in the experience of HIV. Our research suggests that the receipt of
      housing assistance has ramifications for women's engagement in care, and for
      their health. Women not receiving aid often move frequently in and out of
      homelessness, or "double up" with others in complex household arrangements to
      share costs. Women with long-term housing assistance, while still struggling
      financially, possess a stable base from which to approach daily life and HIV
      care. This account suggests a need for empirical research assessing the impact of
      local variations in housing assistance on specific health outcomes for those with
      HIV. It also highlights the importance of understanding local contexts when
      designing housing interventions at both the individual and structural levels.

PMID- 17510788
TI  - Can a laboratory measure of emotional processing enhance the statistical
      prediction of aggression and delinquency in detained adolescents with callous
      unemotional traits?
AB  - In this cross-sectional study, we investigated whether the combination of the
      presence of callous-unemotional (CU) traits and emotional deficits to distressing
      stimuli, assessed by a computerized dot-probe task, enhanced the statistical
      prediction of aggression and delinquency in a sample of 88 detained and
      predominantly African-American (68%) adolescents (M age = 15.57; SD = 1.28).
      Overall, self-reported CU traits were associated with self-report measures of
      aggression and delinquency, but not with official records of arrests. However,
      there was an interaction between CU traits and emotional deficits for predicting
      self-reported aggression, self-reported violent delinquency, and a record of
      violent arrests. Youth high on CU traits and who showed a deficit in their
      responses to visual depictions of distress showed the highest levels of
      aggression and violent delinquency.

PMID- 17510789
TI  - Brain magnetic resonance in the diagnostic evaluation of mitochondrial
      encephalopathies.
AB  - Brain MR imaging techniques are important ancillary tests in the diagnosis of a
      suspected mitochondrial encephalopathy since they provide details on brain
      structural and metabolic abnormalities. This is particularly true in children
      where non-specific neurologic symptoms are common, biochemical findings can be
      marginal and genetic defects may be not discovered. MR imaging modalities include
      conventional, or structural, imaging (MRI) and functional, or ultrastructural,
      imaging (spectroscopy, MRS; diffusion, DWI-ADC; perfusion, DSCI--ASL). Among them
      MRI and MRS are the main tools for diagnosis and work up of MD, and this review
      will focus mainly on them. The MRI findings of MD are very heterogeneous, as they
      depend on the metabolic brain defects, age of the patient, stage and severity of
      the disease. No correlation has been found between genetic defects and
      neuroimaging picture; however, some relationships between MR findings and
      clinical phenotypes may be identified. Different combinations of MRI signal
      abnormalities are often encountered but the most common findings may be
      summarized into three main MR patterns: (i) non-specific; (ii) specific; (iii)
      leukodystrophic-like. Regarding the functional MR techniques, only proton MRS
      plays an important role in demonstrating an oxidative metabolism impairment in
      the brain since it can show the accumulation of lactate, present as a doublet
      peak at 1.33 ppm. Assessment of lactate should be always performed on brain
      tissue and on the ventricular cerebral spinal fluid. As for MRI, metabolic MRS
      abnormalities can be of different types, and two distinct patterns can be
      recognized: non-specific and specific. The specific metabolic profiles, although
      not frequent to find, are highly pathognomonic of MD. The un-specific metabolic
      profiles add value to structural images in allowing to define the lesion load and
      to monitor the response to therapy trials.

PMID- 17510790
TI  - Disorders of nuclear-mitochondrial intergenomic communication.
AB  - In the course of evolution, mitochondria lost their independence, and mtDNA
      became "slave" of nDNA, depending on numerous nucleus-encoded factors for its
      integrity, replication and expression. Mutations in any of these factors may
      alter the cross-talk between the two genomes and cause diseases that affect mtDNA
      integrity or expression, being inherited as mendelian traits.

PMID- 17510791
TI  - Putting the system back into systems change: a framework for understanding and
      changing organizational and community systems.
AB  - Systems change has emerged as a dominant frame through which local, state, and
      national funders and practitioners across a wide array of fields approach their
      work. In most of these efforts, change agents and scholars strive to shift human
      services and community systems to create better and more just outcomes and
      improve the status quo. Despite this, there is a dearth of frameworks that
      scholars, practitioners, and funders can draw upon to aid them in understanding,
      designing, and assessing this process from a systemic perspective. This paper
      provides one framework--grounded in systems thinking and change literatures--for
      understanding and identifying the fundamental system parts and interdependencies
      that can help to explain system functioning and leverage systems change. The
      proposed framework highlights the importance of attending to both the deep and
      apparent structures within a system as well as the interactions and
      interdependencies among these system parts. This includes attending to the
      dominant normative, resource, regulative, and operational characteristics that
      dictate the behavior and lived experiences of system members. The value of
      engaging critical stakeholders in problem definition, boundary construction, and
      systems analysis are also discussed. The implications of this framework for
      systems change researchers and practitioners are discussed.

PMID- 17510792
TI  - Lessons learned in systems change initiatives: benchmarks and indicators.
AB  - Measuring progress toward systems change, sustainable efforts that address root
      causes of an issue by changing policies and practices, is a difficult task for
      communities, evaluators, and foundations. Tracking and documenting changes in
      resources, power, policy, sustainable funding, structured relationships and
      roles, and underlying values require multi-level analyses. Systems change
      analysts must consider at least four "strata" at once: (1) events and trends, (2)
      patterns of interaction, (3) context and cultural or social models, and (4) the
      systems themselves. In this paper we provide a brief overview of systems change;
      a discussion of collaboratives as one "engine" of social change; a discussion of
      benchmarks and indicators of collaboratives focused on systems change; and
      suggestions for further research. The analysis draws upon several analytic
      frameworks described in the literature. We illustrate these concepts with
      examples from six systems change initiatives funded by The California Endowment.
      The need for further research is outlined.

PMID- 17510793
TI  - Systems change reborn: rethinking our theories, methods, and efforts in human
      services reform and community-based change.
AB  - This article introduces the reader to this special issue on Systems Change and
      highlights six lessons learned about theory, methods, and interventions for
      systems change that emerged across the included articles. The value of a systems
      approach to systems change is examined, including the need for frameworks,
      methods, and change activities that attend to the characteristics of systems.

PMID- 17510794
TI  - Polysaccharide structural variability in mycobacteria: identification and
      characterization of phosphorylated mannan and arabinomannan.
AB  - Arabinomannan (AMannan) and mannan (Mannan) are major polysaccharides antigens of
      the mycobacterial capsule. They are highly related to the lipoarabinomannan (LAM)
      and lipomannan (LM) lipoglycans of the cell wall, known to participate to the
      immunopathogenesis of mycobacterial infections. Here we present the
      identification of two related polysaccharides from Mycobacterium kansasii that co
      purified with AMannan and Mannan. Structural analysis using GC, MALDI-MS and NMR
      clearly established these molecules as non-acylated phosphorylated AMannan and
      Mannan designated P-AMannan and P-Mannan, respectively. These glycoconjugates
      represent a new source of polysaccharide structural variability in mycobacteria
      and constitute unique tools for structure-activity relationship studies in order
      to investigate the role of fatty acids in the biological functions of LAM and LM.
      The potential participation of these polysaccharides in influencing the outcome
      of the infection is also discussed.

PMID- 17510795
TI  - Chest compression force of trained and untrained CPR rescuers.
AB  - The objective of this study was to measure the force exerted by 83 trained CPR
      rescuers and 104 untrained adult laypersons (college students and staff). A
      bathroom scale was used to measure the force exerted by these subjects with their
      hands on the bathroom scale in the CPR position. The weight range for both groups
      was the same. Of the trained rescuers, 60% pressed with more than 125 lbs,
      whereas only 37% of the laypersons pressed with more than 125 lbs. In view of the
      American Heart Association (AHA) guidelines (2000) to depress the chest 1.5 to 2
      inches, which requires 100-125 lbs, it would appear that most laypersons do not
      exert enough force for effective CPR.

PMID- 17510796
TI  - HLA DRB1*13 as a risk factor for type 1 autoimmune hepatitis in North American
      patients.
AB  - Our goal was to determine if HLA DRB1*13 is associated with autoimmune hepatitis
      in North American patients. Two hundred and ten adults with definite type 1
      autoimmune hepatitis were typed by DNA-based techniques, and the frequency of HLA
      DRB1*13 in patients without DRB1*03 and DRB1*04 was compared to that in 396
      patients with eight other chronic liver diseases and 102 normal individuals. HLA
      DRB1*13 occurred more commonly in the autoimmune patients who lacked DRB1*03 and
      DRB1*04 than normal subjects who were similarly restricted (56% vs. 27%, P =
      0.007). The frequency of HLA DRB1*13 was higher in autoimmune patients without
      DRB1*03 and DRB1*04 than in patients with other chronic liver diseases who were
      similarly restricted (59% vs. 32%, P = 0.01). Only patients with primary
      sclerosing cholangitis had a comparable occurrence of HLA DRB1*13. In conclusion,
      HLA DRB1*13 may be a genetic risk factor for some white North American patients
      with type 1 autoimmune hepatitis.

PMID- 17510798
TI  - The benefit of the supplementation of perioperative branched-chain amino acids in
      patients with surgical management for hepatocellular carcinoma: a preliminary
      study.
AB  - The aim of this work was to study the benefit of supplementation with a branched
      chain amino acids enriched nutrient mixture on the physical and mental condition
      following hepatic surgery in patients with hepatocellular carcinoma (HCC). A
      total of 41 patients with HCC who underwent hepatic surgery (36 hepatic resection
      and five radiofrequency ablation therapy) were enrolled in this comparative
      study. These patients were divided into two groups: 13 patients received
      perioperative supplementation of a branched chain amino acids enriched nutrient
      mixture (AEN group) and 28 patients did not (control group). Between these two
      groups, laboratory data, postoperative complications and the length of hospital
      stay were analyzed comparatively. Restoration of peripheral lymphocyte count and
      serum total cholesterol level at 3 months after the operation was significantly
      faster in the AEN group than in the control group (P < 0.05). The length of
      hospitalization in the AEN group was significantly shorter than in the control
      group (P < 0.05). This preliminary case control study suggested that the
      perioperative supplementation of a branched chain amino acids enriched nutrient
      mixture is of clinical benefit for nutritional support of patients surgically
      managed for HCC in chronic liver disease.

PMID- 17510797
TI  - Chronic inflammation alters the contribution of neurokinin receptor subtypes to
      epithelial function in rat colon.
AB  - We have previously shown that neurokinin-1 (NK1) receptors predominantly mediate
      substance P-induced secretion of the non-inflamed rat colonic mucosa in vitro
      with a gradient in the magnitude of these responses. The aim of this study was to
      examine the effects of chronic inflammation on the contributions of different
      neurokinin receptor subtypes to colonic mucosal secretion. Colitis was induced by
      the intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid in rats,
      reactivated 6 weeks later. Segments of proximal, mid- and distal colon were
      stripped of muscularis propria and mounted in Ussing chambers for measurement of
      short-circuit current. Use of selective agonists suggests that in the chronically
      inflamed rat colon NK1 receptors play a greater role in neurokinin-mediated
      mucosal secretion than do either NK2 or NK3. Selective antagonism implies that
      this is region-specific, with the inflammatory process altering the relative
      contribution of the neurokinin receptor subtypes within each region of the rat
      colon.

PMID- 17510800
TI  - Prevalence of gastroesophageal reflux disease symptoms and uninvestigated
      dyspepsia in Korea: a population-based study.
AB  - Various reports on the prevalence of gastroesophageal reflux disease (GERD) and
      uninvestigated dyspepsia have been conducted in Western countries. We sought to
      determine the frequency of GERD symptoms and uninvestigated dyspepsia in Korea.
      Telephone interviews were conducted with 1,044 individuals. Of all subjects, 7.1%
      reported that GERD symptoms were present at least once a week, and 3.8% at least
      twice a week. The prevalence of heartburn according to educational level and acid
      regurgitation according to age was significantly different (P < 0.05). The
      prevalence of uninvestigated dyspepsia was reported as 12.2%. Dyspepsia was
      divided into subgroups of 34% ulcer-like, 56% dysmotility-like, and 10%
      nonspecific. The occurrence of dyspepsia did not vary according to age, gender,
      educational level and household income. As frequency of GERD symptoms increased,
      quality of life significantly decreased. We concluded that GERD symptoms and
      uninvestigated dyspepsia were prevalent in Korea. The prevalence was similar to
      that of other Asian countries.

PMID- 17510799
TI  - Dichotomizing axons in spinal and vagal afferents of the mouse stomach.
AB  - Visceral sensory input is typically poorly localized. We hypothesized that
      gastric sensory neurons frequently dichotomize, innervating more than one
      anatomically distinct region and contributing to the poor spatial discrimination.
      METHODS: The neurochemical phenotype and projections of gastro-duodenal sensory
      neurons were determined in adult mice. Choleratoxin B (CTB) coupled to different
      fluorophors was injected into fundus, corpus, antrum, and/or distal duodenum.
      Immunoreactivity for TRPV1, neurofilament (N52), calcitonin gene-related peptide
      (CGRP), presence of isolectin B4 (IB4) and labeling for retrograde labels was
      determined. RESULTS: Depending on the distance between injection sites, staining
      for two retrograde tracers was seen in 6-48% of neurons. Most dorsal root
      ganglion (DRG) neurons showed immunoreactivity for TRPV1 and CGRP. In contrast,
      about half of the gastric nodose ganglion (NG) neurons had TRPV1 immunoreactivity
      or showed IB4 labeling with only 10% CGRP-positive neurons. N52 immunoreactivity
      was present in one-fourth of gastroduodenal DRG and NG neurons. CONCLUSION:
      Visceral sensory neurons have neurochemical properties and may project to more
      than one anatomically distinct area. Neurons with such dichotomizing axons may
      contribute to the poor ability to localize or discriminate visceral stimuli.

PMID- 17510801
TI  - Effects of sibutramine on gastric emptying, intestinal motility and rectal tone
      in dogs.
AB  - The aim of this study was to evaluate the effects of sibutramine on gastric
      emptying, small-bowel contractions, rectal tone and compliance, and
      gastrointestinal myoelectrical activity. The study was performed in 14 dogs. It
      was composed of three separate experiments: gastric emptying of liquids and
      gastrointestinal slow waves; small-bowel contractions; and rectal tone and rectal
      compliance. Each experiment included two sessions: a control session and a
      treatment session with sibutramine (5 mg/kg orally) administrated 2 h before the
      study. Sibutramine significantly accelerated liquid gastric emptying at 75 and 90
      min after the meal but did not alter gastrointestinal slow waves. Gastric
      emptying at 75 and 90 min was 61.42 +/- 7.71 and 66.32 +/- 7.67% in the control
      session, and increased to 71.27 +/- 5.14 and 75.93 +/- 5.29% in the session with
      sibutramine (p < 0.05, vs. control). Sibutramine significantly inhibited
      postprandial small-bowel contractions. Sibutramine did not alter the rectal tone,
      but significantly increased rectal compliance. Sibutramine accelerates gastric
      emptying of liquids but inhibits small-bowel contractions. These findings suggest
      the peripheral mechanisms of sibutramine in reducing food intake and causing
      weight loss in obesity patients.

PMID- 17510802
TI  - Moderate alcohol consumption protects against colorectal adenomas in smokers.
AB  - BACKGROUND: Although some studies have shown an association between alcohol
      consumption and colorectal adenomas, the effect of moderate alcohol consumption
      is not well defined, nor is the interaction between alcohol and smoking. AIM: To
      investigate the relationship between different levels of alcohol consumption and
      colorectal adenomas and to determine whether smoking modifies this relationship.
      METHODS: Eligible patients who underwent a complete colonoscopy were included
      (179 cases and 466 controls). Alcohol consumption was obtained from a lifestyle
      questionnaire. Patients were divided into three groups: (1) Abstainers: 0
      drinks/week; (2) Moderate drinkers: > 0 to <7 drinks/week; (3) Heavy drinkers: >
      or = 7 drinks/week. Odds ratios (OR) were calculated using logistic regression,
      controlling for gender, age, body mass index, use of non-steroidal anti
      inflammatory medications. Results were stratified by the number of years smoked.
      RESULTS: The proportion of patients with adenomas was 29.6% in abstainers, 22.1%
      in moderate drinkers, and 36.7% in heavy drinkers. The relationship between
      alcohol consumption and colorectal adenomas varied significantly by smoking
      history. For individuals who had never smoked, heavy drinkers were at
      significantly increased odds of having an adenoma compared to moderate drinkers
      (OR 3.08; 95% CI: 1.50-6.32), while no difference was seen for abstainers (OR
      0.99; 95% CI: 0.52-1.89). Similarly, among individuals who had smoked 1-14 years,
      heavy drinkers were at increased odds of having an adenoma compared to moderate
      drinkers (OR 2.61; 95% CI: 1.04-6.51), and no difference was seen for abstainers
      (OR 1.02; 95% CI: 0.33-3.10). Somewhat unexpectedly, among individuals who had
      smoked for 15 or more years, abstainers were at increased odds of having an
      adenoma compared to moderate drinkers (OR 2.04; 95% CI: 0.91-4.59), while heavy
      drinkers were not at increased odds of having an adenoma (OR 0.73; 95% CI: 0.27
      1.97). CONCLUSIONS: Consumption of less than seven alcohol drinks per week does
      not increase the risk of having a colorectal adenoma. We found evidence in this
      study that moderate alcohol consumption among long-term smokers may potentially
      decrease the risk of an adenoma compared to abstainers.

PMID- 17510803
TI  - Hepatoid adenocarcinoma of the gallbladder.

PMID- 17510804
TI  - The Korean version of the Multicultural Quality of Life Index (MQLI-Kr):
      development and validation.
AB  - Our research team of multilingual and multicultural members designed
      comprehensive, yet efficient, culture-informed, and self-rated Multicultural
      Quality of Life Indexes for both English-speaking individuals and for growing
      immigrant groups in the United States. A Korean version of the Multicultural
      Quality of Life Index (MQLI-Kr) was developed as part of this multilingual
      project. The team tested the MQLI-Kr on 130 Koreans (100 psychiatric patients and
      30 professionals). MQLI-Kr was quite efficient and easy to use. The internal
      consistency attained a Cronbach's alpha of 0.97 for the combined sample. A factor
      analysis yielded one single factor, which accounted for 81.5% of the items'
      variance. The test-retest reliability correlation coefficient of the MQLI-Kr was
      0.85. Significant differences in the mean MQLI-Kr scores were observed between
      the patients' group and the professionals' group (p < 0.001). Thus the results of
      this study showed high feasibility, internal consistency, reliability, and
      discriminant validity for the MQLI-Kr.

PMID- 17510805
TI  - Effect of pH and metal ions on the decomposition rate of S-nitrosocysteine.
AB  - S-nitrosothiols (RSNOs) have many biological functions including platelet
      deactivation, immunosupression, neurotransmission, and host defense. Most of the
      functions are attributed to nitric oxide (NO) release during S-nitrosothiol
      decomposition. As the simplest biologically occurring S-nitrosothiol, S
      nitrosocysteine (CySNO) has been widely used as an NO donor and has also been
      incorporated into biomedical polymers. Knowledge of the CySNO decomposition rate
      is important for assessing the impact of CySNO on various bioengineering
      applications or biological systems. In this work, spectrophotometer measurements
      of CySNO decomposition in the presence of metal ions showed that the
      decomposition rate is highly susceptible to the pH. The maximum decomposition
      occurs near physiological pH (near 7.4) while in the acidic (pH < 6) and alkaline
      (pH > 9) condition CySNO is very stable. This demonstrates that blood provides an
      optimized environment for the decomposition of CySNO leading to the release of
      NO. The CySNO decomposition rate can also be affected by buffers with different
      purity levels in the presence and absence of metal ion chelators-although all
      buffers show the same pH phenomenon of maximizing near physiological pH. An
      equilibrium model of metal ions as a function of pH provides a plausible
      explanation for the pH dependence on the experimental decomposition rate.

PMID- 17510806
TI  - The PPARgamma agonist rosiglitazone impairs colonic inflammation in mice with
      experimental colitis.
AB  - Various animal models showed that peroxisome proliferator-activated receptor
      (PPAR)gamma agonists, when given as a gavage shortly preceding colitis induction,
      protect against inflammatory bowel disease (IBD). We have examined the effects of
      16 days rosiglitazone treatment via the diet prior to dextran sodium sulphate
      (DSS)-induced colitis in mice. After 7 days DSS in the drinking water,
      rosiglitazone-fed mice had lost significantly more weight than control mice.
      Rosiglitazone-treated mice had more diarrhea, weight of colon and spleen were
      increased, and length of colon was decreased. Histology showed that rosiglitazone
      treated mice had more severe colitis, mainly caused by more ulceration, crypt
      loss, and edema. Immunofluorescence showed a loss of tight junction structure
      Zonula Occludens protein 1 (ZO-1) in colons of rosiglitazone-treated mice as
      compared to control mice. Also, serum amyloid P component (SAP) concentrations in
      plasma were increased. However, concentrations of tumor necrosis factor (TNF)
      alpha and interferon (IFN)-gamma in colon homogenates, and TNF-alpha in spleen
      homogenates were significantly decreased, whereas interleukin (IL)-10 in spleen
      homogenates was increased. Other cytokines (IL-2, IL-4, IL-6, IL-12p70 and
      monocyte chemotactic protein (MCP)-1) and myeloperoxidase (MPO) concentrations
      showed no differences. In conclusion, 16 days pretreatment with rosiglitazone
      impaired DSS-induced colitis in mice.

PMID- 17510807
TI  - Long-term follow-up and outcome of a large cohort of patients with common
      variable immunodeficiency.
AB  - Common Variable Immunodeficiency belongs to the group of rare diseases
      encompassing antibody deficiency syndromes of highly variable clinical
      presentation and outcome. The multicenter prospective study on a cohort of 224
      patients with Common Variable Immunodeficiency provides an updated view of the
      spectrum of illnesses which occurred at the clinical onset and over a long period
      of follow-up (mean time: 11 years) and information on the effects of long-term
      immunoglobulin treatment. The mean age at the time of diagnosis was 26.6 years.
      Seventy-five patients were younger than 14 years of age. The mean age at the
      onset of symptoms was 16.9 years. This implicates with a mean diagnostic delay of
      8.9 years. Respiratory tract infections were the most prominent clinical problem
      observed at diagnosis and during the follow-up. Intravenous immunoglobulin
      administration induced a significant reduction in the incidence of acute
      infections, mainly acute pneumonia and acute otitis. However, a progressive
      increase in the prevalence of patients with chronic diseases, mainly sinusitis
      and lung disease, was observed in all age groups, including the pediatric
      population. The morbidity of Common Variable Immunodeficiency due to all
      associated clinical conditions increased over time despite an adequate
      replacement with intravenous immunoglobulins. Our data stressed the need to
      develop international guidelines for the prevention and therapy of chronic lung
      disease, chronic sinusitis, chronic diarrhoea, and chronic granulomatosis in
      patients with humoral immunodeficiencies.

PMID- 17510808
TI  - Standardization and standards for dyes and stains used in biology and medicine.
AB  - The reasons for standardization and the preparation of standards for dyes and
      stains are presented. The national, regional and international standardization
      agencies are described in detail prior to a consideration of why standards should
      be prepared for the field of biomedical staining. An outline is given of the
      standards for information supplied by the manufacturer for in vitro diagnostic
      reagents for biological staining, published by the European Committee for
      Standardization (CEN) in 1999, and in a practically unaltered form by the
      International Organization for Standards (ISO) in 2002. A more detailed
      description is given in Appendix A of the rules governing the work of the
      European Committee for Standardization (CEN) and of the technical co-operation
      between the International Organization for Standardization (ISO) and CEN (The
      Vienna Agreement). Finally, a short list of abbreviations used by CEN and ISO is
      included as Appendix B.

PMID- 17510809
TI  - Revised procedures for the certification of carmine (C.I. 75470, Natural red 4)
      as a biological stain.
AB  - Carmine is one of the original dyes certified by the Biological Stain Commission
      (BSC). Until now it has lacked both an assay procedure for dye content and a
      means to positively identify the dye. The methods for testing carmine in the
      laboratory of the BSC have been revised to include spectrophotometric examination
      at pH 12.5-12.6 to determine that the dye is carmine (lambda(max)=530-335 nm).
      The maximum absorbance of a solution containing 100 mg of dye per liter of water,
      adjusted to pH 12.5-12.6, which provides a relative measure of dye content,
      should lie in the range 1.2 to 1.8. If the dye is not carmine, spectrophotometry
      at pH 1.9-2.1 shows whether it is carminic acid (lambda(max)=490-500 nm) or 4
      aminocarminic acid (lambda(max)=525-530 nm). The latter two dyes, which are also
      called carmine when sold as food colorants, have physical properties different
      from those of true carmine. The functional tests for carmine as a biological
      stain are Orth's lithium-carmine method for nuclei, Southgate's mucicarmine
      method for mucus, and Best's carmine method for glycogen.

PMID- 17510810
TI  - Effects of hyperoxia on postnatal intestinal development.
AB  - Fetuses develop in a marked hypoxic environment in utero. Premature infants often
      require high concentrations of oxygen to survive and develop in an environment
      that would be considered an oxygen stress for the fetus. Postnatal hyperoxia
      alters organ development, but there is minimal research regarding the role of
      hyperoxia in intestinal development. We attempted to determine whether postnatal
      hyperoxia exposure alters intestinal growth and function by using a reliable,
      objective and sensitive set of methods to study region-specific postnatal
      intestinal maturation. Rat pups born naturally were placed in continual exposure
      to room air (normoxia) or 85% oxygen (hyperoxia) immediately after birth. Pups
      were sacrificed at 1 and 2 weeks of age. Intestines were removed and fixed in
      formalin. Average mucosal, submucosal, and muscularis thicknesses were measured
      on hematoxylin and eosin stained sections. Immunohistochemistry was performed
      using antibodies against NOS II. The staining intensity was determined and
      quantified for site-specific regions of intestinal sections. No differences in
      mucosal thickness, submucosal thickness, or muscularis thickness were measured in
      the duodenum, jejunum or colon at any age. At two weeks of age, the thickness of
      the ileal mucosa was significantly greater in the group reared in 85% oxygen, and
      the group exposed to room air demonstrated significantly greater NOS II protein
      concentration than the hyperoxia group within the distal villus, proximal
      villus/crypts, submucosa, and muscularis in the distal small intestine.

PMID- 17510811
TI  - A two-color acid-free cartilage and bone stain for zebrafish larvae.
AB  - Traditionally, cartilage is stained by alcian blue using acidic conditions to
      differentiate tissue staining. The acidic conditions are problematic when one
      wishes to stain the same specimen for mineralized bone with alizarin red, because
      acid demineralizes bone, which negatively affects bone staining. We have
      developed an acid-free method to stain cartilage and bone simultaneously in
      zebrafish larvae. This method has the additional advantage that PCR genotyping of
      stained specimens is possible.

PMID- 17510812
TI  - Chemically induced premature chromosome condensation in short-term cultured human
      peripheral lymphocytes: applications to biodosimetry.
AB  - We describe here the chemical induction of premature condensed chromosomes in
      human peripheral lymphocytes after culture for 6 h. Many have attempted this
      induction without culture or with short-term culture, because this technique
      permits prompt cytogenetic biodosimetry of radiation accidents. Lymphocytes were
      separated from blood, incubated in the presence of phytohemagglutinin, ATP, and
      p34(cdc2)/cyclin B kinase, then treated with calyculin A during the last hour.
      The culture medium was supplemented with a lower concentration of fetal calf
      serum than conventionally used to minimize its possible interference with the
      effects of these drugs. We obtained, rarely, a suitable morphology of premature
      chromosome condensation in short-term cultured lymphocytes for conventional
      chromosome aberration analysis.

PMID- 17510813
TI  - Certification procedures for nuclear fast red (Kernechtrot), CI 60760.
AB  - Nuclear fast red (CI 60760), also known as Kernechtrot, is commonly used in
      conjunction with an excess of aluminum ions as a red nuclear counterstain
      following histochemical procedures that yield blue products. The dye has also
      been used as a histochemical and colorimetric reagent for calcium. Unsatisfactory
      samples of nuclear fast red are encountered occasionally, and confusion has
      resulted from applying the name of the dye to neutral red (CI 50040), an
      unrelated compound with different properties. Tests for the identity and
      performance of nuclear fast red have been developed in the laboratory of the
      Biological Stain Commission. The Commission will now accept samples submitted by
      vendors for certification. We describe here the spectrophotometric,
      chromatographic and biological staining methods that are used to identify and
      test nuclear fast red.

PMID- 17510817
TI  - Influences of denucleation on contact force of facet joints under whole body
      vibration.
AB  - To investigate the influence of the injured disc, frequency, load and damping on
      the facet contact forces of the low lumbar spine on the condition of whole body
      vibration, a detailed 3-D nonlinear finite element model was created based on the
      actual geometrical data of embalmed vertebrae of lumbar spine. The denucleation
      and facetectomy, together with removal of the capsular ligaments was employed to
      mimic the injury conditions of lumbar spine after surgery. The compression cyclic
      force was assumed to mimic the dynamic loads of transport vehicles. The results
      show that the high frequency vibration might increase both of the value and the
      vibration amplitude of facet contact forces of the lumbar spine under whole body
      vibration. The nucleus removal may increase significantly the facet contact
      forces. Although damping can decrease the vibration amplitude of facet contact
      forces for intact models, it has less effect on the vibration amplitude of facet
      contact force for the denucleated models. The denucleation of intervertebral
      discs is more harmful to the facet articulation on the condition of whole body
      vibration.

PMID- 17510818
TI  - Learning new visuo-motor gains at early and late working age.
AB  - Modern workplaces often require adaptation to novel visuo-motor transformations.
      Findings on age-related variations of such adaptation are rather inconsistent,
      suggesting that whether or not age-related impairments do occur depends on
      boundary conditions. This paper examined the hypotheses that age-related
      variations affect primarily strategic adjustments to novel transformations and
      can be found for complex (non-linear) transformations, but not for simple
      (linear) ones. After a practice period with linear and non-linear visuo-motor
      transformations, open-loop performance, after-effects and explicit knowledge were
      examined. Consistent with previous findings, older participants had longer
      movement times and shorter open-loop amplitudes, more so for long than for short
      target amplitudes. However, the study did not find any age-related variation of
      adaptation to a novel visuo-motor gain. Regarding adaptation to a non-linear
      transformation, the findings suggest slightly superior explicit knowledge of
      younger adults and the development of slightly more efficient closed-loop
      processes in the course of practice.

PMID- 17510819
TI  - Predictors of perceived effort in the shoulder during load transfer tasks.
AB  - The mechanism of muscular effort perception in the shoulder was examined in this
      experiment. Two shoulder biomechanical models and experimental muscle activity
      data were used to assess physical exposure for a series of reaching tasks. Effort
      perception was quantitatively correlated to these measures of physical loading,
      both at the resultant torque (r(2) = 0.50) and muscle activity model-based muscle
      force predictions (MFPs): r(2) = 0.42, electromyography (EMG): r(2) = 0.26)
      levels. Muscle data did not explain variation in effort perception more fully
      than torque data. The inclusion of subject and task variables improved the
      ability of each model to explain variability in effort perception (torque: r(2) =
      0.74; MFP: r(2) = 0.67, EMG: r(2) = 0.64). These results suggest that effort
      perception may not be fully explained by only an image of the motor command, but
      is rather a complex integrative quantity that is affected by other factors, such
      as posture and task goals, which may be dependent on sensory feedback.

PMID- 17510820
TI  - Nursing staff's perception of changes in patient transfer habits after a course -
      a phenomenological-hermeneutic study.
AB  - The objective of the study was to illuminate nursing staff's perception of
      changes after a course in patient transfer. The learning process took the form of
      self-experience focusing on the manner of supporting the patient to move
      independently. A total of 20 participants, who had answered a previously
      administered questionnaire, were chosen for interviews. The themes concerned the
      meaning of changing transfer habits. A phenomenological-hermeneutic analysis
      method showed that changes focused on the patient's body, the staff member's own
      body or cooperation with the patient. Awareness of one's own body and confidence
      in one's own ability seem to indicate differences in the manner of supporting the
      patient to move. The changes in transfer habits varied in content and meaning
      from person to person, depending on the focus during the transfer. These findings
      can contribute to an understanding of how change takes place after an educational
      intervention.

PMID- 17510821
TI  - Peripheral arterial tone as an on-line measure of load in a simulated flight
      task.
AB  - Variations in continuous and discrete flight demands were investigated in a
      simulated flight mission measuring peripheral arterial tone (PAT) from the tip of
      the finger. A total of 12 participants performed a computer-simulated
      agricultural flight task. They were required to fly over a specific lane of a
      simulated corn field (continuous task) and change lanes in response to flags,
      which appeared at varying intervals (discrete task). The difficulty of the flight
      task was manipulated by varying the airplane control (single- vs. dual-axis
      control), while the difficulty of the discrete task was manipulated by varying
      the amount of lateral change signalled by the flag. PAT amplitude was lower in
      the difficult level of the continuous task and was further attenuated following
      the appearance of the flag only when a change in the flight position was
      required. These results suggest the potential utility of PAT as an on-line
      measure of the joint continuous and discrete demands of a flight mission.

PMID- 17510822
TI  - Text - background polarity affects performance irrespective of ambient
      illumination and colour contrast.
AB  - In a series of experiments, proofreading performance was consistently better with
      positive polarity (dark text on light background) than with negative polarity
      displays (light text on dark background). This positive polarity advantage was
      independent of ambient lighting (darkness vs. typical office illumination) and of
      chromaticity (black and white vs. blue and yellow). A final experiment showed
      that colour contrast (red text on green background) could not compensate for a
      lack of luminance contrast. Physiological measures of effort and strain
      (breathing rate, heart rate, heart rate variability and skin conductance level)
      and self-reported mood, fatigue, arousal, eyestrain, headache, muscle strain and
      back pain did not vary as a function of any of the independent variables,
      suggesting that participants worked equally hard in all experimental conditions,
      so that the interpretation of the primary performance measure was unlikely to be
      contaminated by a performance-effort trade-off.

PMID- 17510823
TI  - Situational awareness ability and cognitive skills training in a complex real
      world task.
AB  - Successful performance in complex dynamic environments depends on domain
      dependent factors, such as situational awareness (SA). Underlying SA in a domain
      are domain-independent cognitive abilities in perception, memory, attention and
      executive control. Individuals with lower underlying ability perform relatively
      poorly in complex dynamic real-world tasks. The first experiment examined whether
      cognitive skills training could overcome limitations in underlying SA ability
      that impact on complex dynamic task performance. Participants were taught a mix
      of cognitive management strategies (e.g. divided and focused attention and visual
      search) in a simulated air traffic control task. A second experiment investigated
      the link between underlying SA ability, TRACON and SAGAT, a widely used measure
      of domain-specific SA. In a third experiment, the focus was on encouraging
      participants to plan ahead and consider the interrelations of elements (aircraft)
      in the environment. Whilst both training methods ameliorated the negative impact
      that lower SA ability had on complex dynamic task performance, the results of the
      third study indicated that this may have been achieved through improved planning
      behaviour. Finally, participants with higher underlying SA ability performed well
      irrespective of training condition.

PMID- 17510824
TI  - Effectiveness of a participatory ergonomics intervention in improving
      communication and psychosocial exposures.
AB  - A participatory ergonomics programme was implemented in an automotive parts
      manufacturing factory in which an ergonomics change team was formed, composed of
      members from management, the organized labour union and the research team. It was
      hypothesized that the participatory nature of this change process would result in
      enhanced worker perceptions of workplace communication dynamics, decision
      latitude and influence, which in conjunction with anticipated mechanical exposure
      reductions would lead to reduced worker pain severity. Utilizing a sister plant
      in the corporation as a referent group, a quasi-experimental design was employed
      with a longitudinal, repeat questionnaire approach to document pre-post
      intervention changes. Nine participatory activities (psychosocial interventions)
      were implemented as part of the process. Communication dynamics regarding
      ergonomics were significantly enhanced at the intervention plant compared to the
      referent plant. However, there were no significantly different changes in worker
      perceptions of decision latitude or influence between the two plants, nor did
      pain severity change. Possible explanations for these results include limited
      intervention intensity, context and co-intervention differences between the two
      plants, high plant turnover reducing the statistical power of the study and lack
      of sensitivity and specificity in the psychosocial measures used. Further
      research should include the development of psychosocial tools more specific to
      participatory ergonomic interventions and the assessment of the extent of change
      in psychosocial factors that might be associated with improvements in pain.

PMID- 17510825
TI  - Muscle fatigue during intermittent isokinetic shoulder abduction: age effects and
      utility of electromyographic measures.
AB  - Most existing evidence regarding the effects of age on muscular fatigue has
      focused on prolonged isometric contractions, repeated maximum dynamic
      contractions and individuals beyond traditional retirement age (>65 years). In
      the present study, age-related differences in muscle fatigue during submaximal
      dynamic efforts were examined. There were 24 younger (18-25 years) and 24 older
      (55-65 years) participants, all of whom were healthy and active, with equal
      numbers of each gender within each age group. Participants performed repetitive,
      intermittent shoulder abductions until exhaustion, at peak moments of 30% and 40%
      of individual maximum voluntary isokinetic contraction (MVIC) and with cycle
      durations of 20 and 40 s. Fatigue development was determined based on changes in
      MVIC, electromyographic (EMG) signals and ratings of perceived discomfort (RPD).
      Following the exhaustive exercises, strength recovery was monitored using a
      series of MVICs over a 15-min period. Results indicated the existence of an age
      related fatigue resistance, with the older group demonstrating significantly
      slower rates of MVIC decline and RPD increase and smaller modifications in EMG
      based fatigue measures. These age effects were generally more pronounced at the
      higher effort level. Main effects of effort level and cycle duration were also
      significant, while gender effects appeared to be marginal. Rates of strength
      recovery were not significantly influenced by age. In addition, the utility of
      standard EMG-based fatigue measures was assessed. Findings indicated that time
      dependent changes in static and dynamic EMG-based measures were roughly
      comparable in terms of sensitivity and variability, supporting the use of
      standard EMG analyses for fatigue monitoring during intermittent dynamic
      contractions.

PMID- 17510826
TI  - Effects of varying the threshold of alarm systems and workload on human
      performance.
AB  - The purpose of this research was to investigate the effects of varying the
      threshold of alarm systems and workload on human response to alarm signals and
      performance on a complex task. A receiver operating characteristic (ROC) curve
      was selected to reflect the sensitivity of the alarm system. The threshold of the
      alarm system was manipulated by changing the value of beta along the ROC curve. A
      total of 84 students participated in experiment 1 and 48 students participated in
      experiment 2. Participants performed a compensatory-tracking, a resource
      management and a monitoring task. As expected, results showed that participants
      responded significantly faster to true alarm signals when they were using the
      system with the highest threshold under low-workload conditions. Results also
      indicated that changing the threshold of the alarm system had a significant
      effect on overall performance and this effect was greater under high-workload
      conditions. However, contrary to expectations, the highest level of performance
      was achieved by setting the threshold at a low level. Results from both
      experiments revealed that the advantage of faster alarm reaction time as a result
      of increasing the system's threshold was lost because of its increased
      probability of missed events.

PMID- 17510829
TI  - The sibling experience: growing up with a child who has pervasive developmental
      disorder or mental retardation.
AB  - Parents raising a child with significant developmental challenges are profoundly
      aware of the often sustained impact of that child's special needs upon their
      other children. Supported by recent research on siblings of developmentally
      challenged children, clinicians are advocating family-based interventions that
      take into account the needs of siblings. This article reviews the experience of
      siblings who live with brothers or sisters diagnosed with pervasive developmental
      disorder or mental retardation. Contributions from research on typical siblings
      are drawn upon when appropriate. Six domains of the sibling experience are
      identified. These domains explore relational shifts within sibling relationships
      and through the expectable differential parental treatment of each child. Shifts
      considered in this review include the interrelationships with the extended
      family, peers, and friendships, all of which contribute to shaping the meaning
      that siblings give to living with developmentally challenged brothers or sisters
      across time.

PMID- 17510830
TI  - Hallucinations from a cognitive perspective.
AB  - Although the phenomenological diversity of hallucinations has been well
      documented, experimental investigations into their cognitive underpinnings have
      not yet reflected this complexity. Our goal in this review is to contrast the
      restricted set of experimental conditions that have been utilized in source
      monitoring studies of hallucinations with their documented phenomenological
      diversity. In particular, we initially focus on the theoretical distinction
      between origin and source that has been recognized at the level of phenomenology,
      and then review the source-monitoring literature within this theoretical
      framework. In addition, we touch on several other aspects of the phenomenological
      diversity of hallucinations that have not yet been sufficiently investigated
      experimentally--namely, intentionality, affect, and motivational factors.
      Finally, we list other methodological problems that may have led to
      inconsistencies in the literature. We conclude with concrete recommendations for
      future source-monitoring investigations of hallucinations.

PMID- 17510831
TI  - Free fall: finding solid ground in the treatment of a patient with catastrophic
      injury.

PMID- 17510832
TI  - Improving treatment for depression in the nursing home population: integrating
      the model of the depression care manager.

PMID- 17510833
TI  - Development and evaluation of a photochemical chamber to examine the toxicity of
      coal-fired power plant emissions.
AB  - When investigating the toxicity of individual particle sources, it is important
      to consider the contribution of both primary and secondary particles. In this
      article, we present the design of a new photochemical chamber that can be used to
      form secondary sulfuric acid particles from diluted coal-fired power plant
      emissions. The chamber is a relatively small, well-mixed flow reactor that can
      fit in a mobile reaction laboratory. It produces high concentrations of hydroxyl
      radical (OH) from the photolysis of ozone (O3) in the presence of water vapor.
      Two chambers were built and tested. A pilot chamber was tested in the laboratory,
      using mixtures of NO and SO2 in air, at concentrations that are approximately 100
      times lower than those in power plant stack emissions. This chamber was able to
      oxidize about 20% of the SO2, thereby producing 1350 microg m(-3) of H2SO4
      particles. Further tests showed that increasing O3 concentrations and residence
      time increased the H2SO4 production. A field chamber was built subsequently and
      used in a toxicological study. Diluted coal-fired power plant emissions were
      introduced in the chamber. Over 19 days of exposure, the chamber, on average,
      converted 17% of the supplied SO2 emissions and produced an average of 350 microg
      m(-3) of H2SO4 particles. Particle losses were determined for the pilot chamber,
      using artificial particles whose size ranged from 50 to 1000 nm. The determined
      losses ranged from 21 to 42%, with no trend between the amount of particle loss
      and particle size. Losses for the field chamber, estimated using model
      calculations, were found to be similar to those of the pilot chamber.

PMID- 17510834
TI  - Development of an exposure system for the toxicological evaluation of particles
      derived from coal-fired power plants.
AB  - To investigate the toxicity of particles originating from coal-fired power plants
      it is necessary to consider the effects of both primary particles and secondary
      components formed in the air through atmospheric reactions. This report describes
      a new exposure system that can be used to expose animals to both directly emitted
      particles and to secondary particles. The system consists of three main
      components. The first is a sampling system to continuously collect and dilute
      power plant stack emissions. The second is a reaction laboratory that contains
      reaction chambers to simulate atmospheric reactions. The following atmospheric
      reactions were simulated: (1) the oxidation of sulfur dioxide to form sulfuric
      acid, (2) the neutralization of sulfuric acid by ammonia, and (3) the reaction of
      alpha-pinene with ozone to form secondary organic aerosol. Using these chambers
      with the diluted emissions, different typical atmospheric scenarios can be
      simulated. The final component is a mobile toxicology laboratory where animals
      are exposed to the resulting test aerosols. We report here the characteristics of
      the test aerosol exposures obtained at a coal-fired electric power plant.
      Particle exposures were characterized for concentrations of mass, elements,
      elemental carbon, organic species, inorganic ions, strong acidity, particle
      number, and size distributions. Mass concentrations ranged from a few micrograms
      per cubic meter for a scenario of primary emissions only, to about 250 microg m(
      3) for the most complex scenario. We show that the different scenarios produced a
      large variation in the composition of the test aerosol, thus potentially changing
      the toxicity of the emissions.

PMID- 17510835
TI  - Variation in heart rate regulation and the effects of particle exposure in inbred
      mice.
AB  - Altered autonomic control of heart rate (HR) rhythm during exposure to
      particulate matter (PM) has been suggested in human and animal studies. Our lab
      has shown strain variation in HR regulation between quiescent C3H/HeJ (C3) and
      C57BL/6J (B6) mice: that is, C3 mice show a consistently higher HR by
      approximately 80 bpm compared with B6 mice during a normal 24-h circadian cycle.
      In the current study, we hypothesize that the balance between sympathetic and
      parasympathetic control of HR during PM exposure varies between C3 and B6 mice.
      Radiotelemeters were implanted in C3 and B6 mice to measure HR responses and HR
      variability (HRV) parameters during successive 3-h exposures to filtered air (FA)
      or carbon black (CB, < 300 mug/m3). Exposures were repeated following
      administration of saline or parasympathetic (PS; atropine, 0.5 mg/kg i.p.) and
      sympathetic (S; propranolol, 1 mg/kg i.p.) blockade to study the autonomic
      regulation of HR during CB exposure. During FA exposure with saline, a
      significantly (p < .05) greater 3-h average HR response (bpm +/- SEM) occurred in
      C3 compared with B6 mice (496 +/- 22 vs. 427 +/- 3). With PS blockade, the strain
      difference between C3 and B6 mice was not evident (485 +/- 23 vs. 503 +/- 61).
      With S blockade, the 3-h average HR responses for C3 mice were significantly (p <
      .05) reduced compared with saline (413 +/- 18 vs. 392 +/- 15 for B6). During CB
      exposure with saline, HR responses were again significantly (p < 0.05) elevated
      in C3 compared with B6 mice, but these HR responses were not different relative
      to FA exposure. With S blockade, HR was significantly (p < .05) elevated in B6
      mice during CB relative to FA, but was unchanged in C3 mice. Collectively, these
      results suggest that strain variation in HR regulation is due to a robust PS tone
      evident in B6 mice and a predominant S tone in C3 mice. Furthermore, CB exposure
      alters HR regulation in B6 mice by modulating a withdrawal of PS tone. Finally,
      strain variation in HR between B6 and C3 mice in responding to acute PM exposure
      implies that robust genetic determinants modulate altered autonomic regulation in
      susceptible individuals.

PMID- 17510836
TI  - Testing strategies to establish the safety of nanomaterials: conclusions of an
      ECETOC workshop.
AB  - The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC)
      convened a workshop in Barcelona, Spain, in November 2005 to develop testing
      strategies to establish the safety of nanomaterials. It brought together about 70
      scientific and clinical experts from industry, academia, government agencies,
      research institutes, and nongovernmental organizations. The primary questions to
      be addressed were the following: What can we do today, and what do we need
      tomorrow? The three major themes of the workshop were: (1) the need for enhanced
      efforts in nanomaterial characterization; (2) methodologies for assessments of
      airborne and internal exposures to nanomaterials; and (3) evaluation of the
      hazard potential--primarily focusing on pulmonary or dermal routes of exposures.
      Some of the summary conclusions of the workshop included the following: For the
      development of nanoparticle characterization, the working definition of
      nanoparticles was defined as < 100 nm in one dimension or < 1000 nm to include
      aggregates and agglomerates. Moreover, it was concluded that although many
      physical factors can influence toxicity, including nanoparticle composition, it
      is dissolution, surface area and characteristics, size, size distribution, and
      shape that largely determine the functional, toxicological and environmental
      impact of nanomaterials. In addition, most of the information on potential
      systemic effects has thus far been derived from combustion-generated particles.
      With respect to the assessment of external exposures and metrics appropriate for
      nanoparticles, the general view of the meeting was that currently it is not
      possible or desirable to select one form of dose metric (i.e., mass, surface
      area, or particle number) as the most appropriate measure source. However, it was
      clear that the surface area metric was likely to be of interest and requires
      further development. In addition, there is a clear and immediate need to develop
      instruments which are smaller, more portable, and less expensive than the
      currently available state of the art instrumentation. With regard to a general
      testing approach for human health hazard evaluation of nanoparticles, a first
      step to determine potency may include a prioritization-related in vitro screening
      strategy to assess the possible reactivity, biomarkers of inflammation and
      cellular uptake of nanoparticles; however this process should be validated using
      in vivo techniques. A Tier 1 in vivo testing strategy could include a short-term
      inhalation or intratracheal instillation of nanoparticles as the route of
      exposure in the lungs of rats or mice. The endpoints that should be assessed
      include indices of lung inflammation, cytotoxicity, and cell proliferation, as
      well as histopathology of the respiratory tract and the major extrapulmonary
      organs. For Tier 2 in vivo testing for hazard identification, a longer term
      inhalation study is recommended, and this would include more substantive
      mechanistic endpoints such as determination of particle deposition,
      translocation, and disposition within the body. Additional studies could be
      designed with specific animal models to mimic sensitive populations. With regard
      to dermal exposures, currently there is little evidence that nanoparticles at a
      size exceeding 100 nm penetrate through the skin barrier into the living tissue
      (i.e., dermal compartment). The penetration of nanoparticles at a size less than
      100 nm should be a topic of further investigation. Moreover, considering the
      impacts of dermal exposures and corresponding hazard potential of nanoparticles,
      it must be taken into consideration that the dermal uptake of nanoparticles will
      be an order of magnitude smaller than the uptake via the inhalation or oral
      routes of exposure. For the evaluation of the health risk of nanoparticles, it
      has to be determined whether they are harmful to living cells and whether, under
      real conditions, they penetrate through the skin barrier into the living tissue.
      For the evaluation of the penetration processes, in principle, three methods are
      available. Using the method of differential stripping, the penetration kinetics
      of nanoparticles in the stratum corneum and the hair follicles can be evaluated.
      This analysis can be carried out in vivo. Diffusion cell experiments are an
      efficient method for in vitro penetration studies. Also, laser scanning
      microscopy is well suited to test penetration kinetics, although requiring
      fluorescent-labeled nanoparticles. Emerging topics such as (1) environmental
      safety testing, (2) applications of nanoparticles for medical purposes, and (3)
      pathways of inhaled nanoparticles to the central nervous system were also briefly
      addressed during this workshop. However, it has become clear that these topics
      should be the subjects of separate workshops and they are not further addressed
      in this report.

PMID- 17510837
TI  - Involvement of NADPH oxidase and iNOS in rodent pulmonary cytokine responses to
      urban air and mineral particles.
AB  - We have investigated the potential of two complex mineral particles (feldspar and
      mylonite), quartz (Min-U-Sil), and suspended particulate matter (SRM-1648) (SPM)
      from urban air to induce inflammatory cytokine responses in primary rat alveolar
      type 2 cells and alveolar macrophages, and the involvement of cellular formation
      of free radicals in these responses. All particle types induced an increased
      release of interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2 from
      type 2 cells. Diphenyleneiodonium chloride (DPI), a selective inhibitor of NADPH
      oxidase, reduced the IL-6 and MIP-2 responses to quartz, SPM and mylonite. N-(3
      [Aminomethyl] benzyl) acetamidine (1400W), a selective inhibitor of inducible
      nitric oxide synthase (iNOS), significantly reduced the Il-6 response to SPM and
      feldspar in the type 2 cells. The macrophages displayed significantly increased
      TNF-alpha and MIP-2 release upon exposure to quartz or SPM. Here, DPI
      significantly reduced the tumor necrosis factor (TNF)-alpha and MIP-2 responses
      to quartz, and the MIP-2 response to SPM. No significant effect of 1400 W was
      detected in the alveolar macrophages. The role of particle-induced cellular
      generation of free radicals in lung cytokine responses was further elucidated in
      mice that lacked either NADPH-oxidase or iNOS as well as in wild-type (wt) mice.
      All particles were able to elicit increased cytokine levels in the
      bronchoalveolar lavage (BAL) fluid of the mice, although the levels depended on
      particle type. The NADPH-oxidase knockout (KO) mice demonstrated a significantly
      lower IL-6 and MIP-2 responses to SPM compared to their respective wt mice. The
      iNOS KO mice displayed significantly reduced IL-6, TNF-alpha, and MIP-2 responses
      to SPM. The overall results indicate the involvement of cellular free-radical
      formation in the pulmonary cytokine responses to particles of varying
      composition.

PMID- 17510838
TI  - Assessment of alterations in barrier functionality and induction of
      proinflammatory and cytotoxic effects after sulfur mustard exposure of an in
      vitro coculture model of the human alveolo-capillary barrier.
AB  - Acute lung injury after sulfur mustard (SM) inhalation is characterized by
      massive, localized hemorrhage and alveolar edema, which implies severe disruption
      of the vascular and distal airway barrier. In this study, we tested a recently
      established in vitro coculture model of the alveolo-capillary barrier for its
      applicability to investigate acute toxic effects of SM at the human respiratory
      unit. The epithelial compartment of cocultures was exposed to varying
      concentrations of SM (0-1000 microM; t = 30 min). Following exposure, functional
      and structural barrier integrity of cocultures was monitored over a period of 24
      h. A 50% reduction of transbilayer electrical resistance (TER) within 12-24 h
      after exposure to 300 microM SM and within 8 h after 1000 microM SM revealed a
      time- and concentration-dependent impairment of barrier functionality, which was
      associated with structural loss of both cell layers. Subsequent quantification of
      interleukin (IL)-6 and IL-8 in cell culture supernatants of exposed cocultures
      showed enhanced liberation of proinflammatory markers. Highest mediator levels
      were detected after 300 microM SM, with pronounced stimulation in the endothelial
      compartment. SM-related cytotoxicity was determined by assessing adenylate kinase
      (AK) release and by quantifying the fraction of DNA-fragmented nuclei using
      terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) and
      nuclear Hoechst staining. Both methods exposed a concentration-dependent increase
      of SM-mediated cytotoxic effects with high effects on endothelial cells. We
      conclude that the described in vitro model reflects important characteristics of
      SM-mediated acute lung injury in vivo and thus can be used to explore involved
      pathophysiological pathways.

PMID- 17510839
TI  - Kinetics of sarin (GB) following a single sublethal inhalation exposure in the
      guinea pig.
AB  - To improve toxicity estimates from sublethal exposures to chemical warfare nerve
      agents (CWNA), it is necessary to generate mathematical models of the absorption,
      distribution, and elimination of nerve agents. However, current models are based
      on representative data sets generated with different routes of exposure and in
      different species and are designed to interpolate between limited laboratory data
      sets to predict a wide range of possible human exposure scenarios. This study was
      performed to integrate CWNA sublethal toxicity data in male Duncan Hartley guinea
      pigs. Specific goal was to compare uptake and clearance kinetics of different
      sublethal doses of sarin (either 0.1 x or 0.4 x LC50) in blood and tissues of
      guinea pigs exposed to agent by acute whole-body inhalation exposure after the 60
      min LC50 was determined. Arterial catheterization allowed repeated blood sampling
      from the same animal at various time periods. Blood and tissue levels of
      acetylcholinesterase, butyrylcholinesterase, and regenerated sarin (rGB) were
      determined at various time points during and following sarin exposure. The
      following pharmacokinetic parameters were calculated from the graph of plasma or
      RBC rGB concentration versus time: time to reach the maximal concentration;
      maximal concentration; mean residence time; clearance; volume of distribution at
      steady state; terminal elimination-phase rate constant; and area under plasma
      concentration time curve extrapolated to infinity using the WinNonlin analysis
      program 5.0. Plasma and RBC t(1/2) for rGB was also calculated. Data will be used
      to develop mathematical model of absorption and distribution of sublethal sarin
      doses into susceptible tissues.

PMID- 17510840
TI  - Toxicological comparisons of cigarettes containing different amounts of vanillin.
AB  - Vanillin is a flavoring agent used in cigarettes. Previous toxicological
      examinations of the effects on the addition of vanillin to tobacco used mixtures
      with several other flavoring agents. In the present work, toxicological
      comparisons were made of experimental cigarettes containing no added vanillin
      against otherwise similar cigarettes with three different amounts of vanillin
      added to the tobacco. The main toxicological comparison was a subchronic
      inhalation study with mainstream smoke in Sprague-Dawley rats (exposures of 150
      mg/m3 of total particulate matter, 6 h exposure per day, for 90 consecutive
      days). Vanillin concentrations in the tobacco of the 4 cigarette types at the end
      of the study were 0, 67, 1233, and 3109 ppm. Additional studies with mainstream
      smoke were Salmonella mutagenicity (5 bacterial strains, both with and without
      metabolic activation, particulate phase only), cytotoxicity of both particulate
      and gas/vapor phases (using the neutral red uptake assay), and analytical
      chemistry (49 analytes, including 5 metals). Similar responses were seen across
      the four cigarette types, and the responses were similar to those previously
      described in the scientific literature. At the same smoke concentration, the
      inhalation exposures produced effectively the same responses, in each of the four
      groups. Most of the changes produced in the 90 days of exposure were resolved in
      a 42-day postinhalation period. The addition of vanillin to tobacco at inclusion
      rates up to 3109 ppm did not influence a broad range of toxicological endpoints.

PMID- 17510841
TI  - Comparative 13-week inhalation study of cigarette smoke from cigarettes
      containing cast sheet tobacco.
AB  - A subchronic, nose-only inhalation study was conducted to compare the effects of
      mainstream smoke from a reference cigarette containing conventional reconstituted
      tobacco sheet at 30% of the finished blend to mainstream smoke from cigarettes
      containing 10% or 15% cast sheet (a specific type of reconstituted tobacco sheet)
      substituted for part of the conventional reconstituted tobacco. Male and female
      Sprague-Dawley rats were exposed for 1 h/day, 5 d/wk, for 13 wk to mainstream
      smoke at 0, 0.06, 0.20, or 0.80 mg wet total particulate matter per liter of air.
      Clinical signs, body and organ weights, clinical chemistry, hematology,
      carboxyhemoglobin (COHb), serum nicotine, plethysmography, gross pathology, and
      histopathology were determined. Exposure to cigarette smoke induced a number of
      changes in respiratory physiology, histopathology, and serum nicotine and COHb
      levels when compared to sham animals. When corresponding dose groups of reference
      and cast sheet mainstream smokes were compared, no biological differences were
      noted. At the end of the exposure period, subsets of rats from each group were
      maintained without smoke exposures for an additional 13 wk (recovery period). At
      the end of the recovery period, there were no statistically significant
      differences in histopathological findings observed between the reference and
      either cast sheet cigarette. Substitution of 10% or 15% cast sheet tobacco for
      conventional reconstituted tobacco sheet does not alter the inhalation toxicology
      of the mainstream smoke when compared to mainstream smoke from a reference
      cigarette containing conventional reconstituted tobacco sheet.

PMID- 17510842
TI  - Characteristics of non-fatal injuries in Leon, Nicaragua - 2004.
AB  - This article describes the epidemiology of injuries collected in the Injury
      Surveillance System in Leon Hospital in Nicaragua. A total of 6659 persons were
      treated for injuries in 2004. It was discovered that 88% of all injuries were
      unintentional, 9% involved interpersonal violence, 2% were self-inflicted and
      0.2% was undetermined. Men accounted for 64.7% of the cases, with the highest
      rate among 20 - 24 year olds (5625.8 per 100,000 inhabitants). Among women, the
      highest rate was in those aged 64 years and older (5324.2 per 100 000
      inhabitants). The most common mechanisms were falls (33.9%), blunt force (26.8%),
      cut/pierce/stab (15.1%) and transportation-related (12.8%). These results
      indicate the need to identify prevention strategies for those injuries that were
      most commonly treated in emergency, such as unintentional falls among older
      women, self-inflicted poisoning among young women and blunt force and
      transportation-related injuries among young men.

PMID- 17510843
TI  - The evaluation of a surveillance system for violent and non-intentional injury
      mortality in Colombian cities.
AB  - Since 2002, the Institute for Peace Promotion and Injury/Violence Prevention
      (CISALVA) at the Universidad del Valle, Cali, Colombia and the Colombia Program
      at Georgetown University have developed and implemented 21 epidemiologically
      based municipal crime observatories in intermediate-sized municipalities in
      Colombia. These crime observatories serve as monitoring centres that provide low
      cost, geo-referenced methods of data collection and analysis, which allow cities
      to develop more responsive policies and prevention programmes and enhance
      governance. This article focuses on the methodology employed and lessons learned
      that may be applicable to similar settings. Worth noting within the results was a
      significant decrease in homicides after the first year of the programme. Whether
      or not such results could be attributed to the method or to the nature of the
      interventions and policy initiatives stemming from it remains open to conjecture.

PMID- 17510844
TI  - Impact of injuries on work performance among the surgical blacksmiths of West
      Bengal.
AB  - The manufacture of surgical instruments is one of the leading small-scale
      industrial sectors in West Bengal, India. The present study was undertaken to
      assess the rate, type and cause of injury incidents among surgical blacksmiths
      and whether these incidents affected the work performance of the blacksmiths. A
      cluster of 216 skilled and 225 unskilled blacksmiths (male), engaged in the
      manufacture of surgical instruments, was selected from Baruipur subdivision as
      study subjects. The study included: 1) completion of a questionnaire; 2)
      measurement of physical parameters; 3) incident records; 4) statistical analysis
      of the data. The present study revealed that the blacksmiths suffered very
      frequently from work-related injuries. The number of injuries that occurred
      during 2004 - 2005 for skilled and unskilled blacksmiths was 1413 and 1610
      respectively. Unskilled blacksmiths were disproportionately affected. These
      injuries resulted in a high rate of lost workdays, i.e. 517 and 742 workdays for
      skilled and unskilled workers respectively. The study thus indicated that
      surgical blacksmiths are highly prone to injuries in their occupation, mostly
      affecting the fingers (23% and 23%) and back region (21.7% and 22%) in both
      groups, which consequently affected their health, productivity and work
      performance.

PMID- 17510845
TI  - Linking drinking to injury--causal attribution of injury to alcohol intake among
      patients in a Swedish emergency room.
AB  - This study analysed the drinking patterns and motivation to change drinking
      behaviours among injury patients who acknowledged alcohol as a factor in their
      injuries. A cross-sectional study was conducted over 18 months at a Swedish
      emergency department. A total of 1930 injury patients aged 18 - 70 years were
      enrolled in the study (76.8% completion rate). Of those who reported drinking,
      10% acknowledged alcohol as a factor in their injury. A patient was more likely
      to report a causal attribution of the injury to alcohol the higher the weekly
      intake and the higher the frequency of heavy episodic drinking. The motivation to
      change variables showed a similar pattern of increased likelihood of attributing
      a causal link of alcohol and injury with increasing discontent with drinking
      behaviours and increasing desire to change drinking behaviours. The findings
      suggest that the ability to measure causal attribution of alcohol to injuries
      could be a promising tool to help patients explore the association between their
      injuries and alcohol use and motivate patients to modify drinking behaviours in
      order to avoid future injuries.

PMID- 17510846
TI  - The effect of seatbelt legislation on hospital admissions with road traffic
      injuries in an oil-rich, fast-developing country.
AB  - The objective of the study was to examine the effect of seat-belt legislation on
      hospital admissions with road traffic injuries and was designed as a
      retrospective descriptive study. All motor vehicle crashes recorded during the
      period 2001 - 2004 were extracted from the Emergency Medical Service Department.
      Details of the crashes, injuries and safety devices used were studied. The
      present study revealed that safety belt usage rates have increased from 8% in
      2001 to 67% in 2004 among patients admitted to hospital with injury after road
      traffic crashes. The admission rate of patients with road traffic injuries per
      100 000 population reduced by 17.7%. The enforcement of the seat-belt legislation
      played a vital role in reduction of hospital admissions due to road traffic
      crashes.

PMID- 17510847
TI  - A randomized trial to assess the effectiveness of an infant home safety
      programme.
AB  - The aim of this study was to test an intervention aimed at addressing the risk of
      injury in infants 2 - 12 months of age. A non-blinded, randomized controlled
      trial was conducted, whereby parents were randomly assigned to either a control
      or one of two intervention groups. Parents completed questionnaires regarding
      safety behaviours and injuries at the 2 (baseline), 6 and 12 month immunization
      visit at the community health unit. During the 2 month visit to the health unit,
      the two intervention groups received a home safety kit containing nine items, an
      instructional brochure and a risk assessment checklist. Subjects randomized to
      the safety kit plus home visit group also received a standardized home visit from
      a community health nurse. Two of the 14 parental safety behaviours showed a
      significant increase in use among parents in the intervention groups. Neither of
      the interventions was associated with a reduction in parent-reported injuries
      among children. It was concluded that home visitation may provide a beneficial
      adjunct to the provision of safety devices and may increase use by parents.

PMID- 17510848
TI  - Road traffic accidents and safety programme in Turkey.

PMID- 17510849
TI  - Frequency of caregiver supervision of young children during play.

PMID- 17510850
TI  - Accidental injury in children: hospital trauma records in a Spanish population.

PMID- 17510851
TI  - Filling know-do gaps in road safety policy in developing countries: a case study
      of Thailand.

PMID- 17510852
TI  - Hospital admissions after paediatric trauma in a developing country: from falls
      to landmines.

PMID- 17510854
TI  - Update on the genus Malassezia.
AB  - Malassezia yeasts are commensals of normal human skin, but also cause pityriasis
      versicolor, seborrhoeic dermatitis and evidence is accumulating that they play a
      significant role in atopic eczema/dermatitis syndrome (AEDS; formerly atopic
      dermatitis). The taxonomy of the genus has changed considerably and is likely to
      change more in the future. Our understanding of the interaction between
      Malassezia and the host demonstrates that it has the paradoxical ability to both
      stimulate and suppress the immune response directed against it and there is a
      fine balance in its existence at the interface between commensalism and
      pathogenicity.

PMID- 17510855
TI  - Fungal infections in solid organ transplantation.
AB  - Fungal infections in solid organ transplant recipients continue to be a
      significant cause of morbidity and mortality. Candida spp. and Aspergillus spp.
      account for most invasive fungal infections. The incidence of fungal infection
      varies with type of solid organ transplant. Liver transplant recipients have
      highest reported incidence of candida infections while lung transplant recipients
      have highest rate of Aspergillus infections. Recent epidemiological studies
      suggest the emergence of resistant strains of candida as well as mycelial fungi
      other than Aspergillus in these patients. The current review incorporates the
      recent changes in the epidemiology of fungal infections in solid organ transplant
      recipients and highlights the newer data on the diagnosis, prophylaxis and
      treatment of fungal infections in these patients.

PMID- 17510856
TI  - Nosocomial fungal infections: epidemiology, diagnosis, and treatment.
AB  - Invasive fungal infections are increasingly common in the nosocomial setting.
      Furthermore, because risk factors for these infections continue to increase in
      frequency, it is likely that nosocomial fungal infections will continue to
      increase in frequency in the coming decades. The predominant nosocomial fungal
      pathogens include Candida spp., Aspergillus spp., Mucorales, Fusarium spp., and
      other molds, including Scedosporium spp. These infections are difficult to
      diagnose and cause high morbidity and mortality despite antifungal therapy. Early
      initiation of effective antifungal therapy and reversal of underlying host
      defects remain the cornerstones of treatment for nosocomial fungal infections. In
      recent years, new antifungal agents have become available, resulting in a change
      in standard of care for many of these infections. Nevertheless, the mortality of
      nosocomial fungal infections remains high, and new therapeutic and preventative
      strategies are needed.

PMID- 17510857
TI  - Evaluation of combined deactivators-supplemented agar medium (CDSAM) for recovery
      of dermatophytes from patients with tinea pedis.
AB  - Using a newly-developed medium, i.e., combined deactivators-supplemented agar
      medium (CDSAM), the viability of dermatophytes in skin scales was evaluated.
      Culture studies were conducted with skin scales collected from 44 patients with
      tinea pedis who had been treated for two weeks with topical antifungal drugs.
      Sixty-four percent of the specimens were mycologically positive on CDSAM, while
      only 23% of these same specimens were positive when cultured on conventional
      Sabouraud's dextrose agar medium (SDA). Alternatively, 36% of all cases were
      negative on both media. The experimental data from this clinical study indicate
      that CDSAM was more useful than SDA in accurately evaluating the efficacy of
      antifungal drugs since the former minimized the residual effects of drug residues
      remaining in the skin samples.

PMID- 17510858
TI  - A colorimetric and spectrophotometric method for in vitro susceptibility testing
      of Aspergillus species against caspofungin.
AB  - The in vitro susceptibility of 45 Aspergillus fumigatus, Aspergillus flavus and
      Aspergillus terreus isolates against caspofungin (CAS) was assessed by the CLSI
      reference method with spectrophotometric reading and by a colorimetric method
      that employed the dye MTT. Perfect agreement was found between the minimal
      effective concentrations (MECs) and the MIC-2 values (50% growth reduction)
      obtained by the MTT method. The agreement found between the MICs obtained by the
      CLSI and the MTT method was dependent on the MIC endpoint used, the antifungal
      agent tested, and the species investigated.

PMID- 17510859
TI  - Biofilm development by clinical isolates of Malassezia pachydermatis.
AB  - Malassezia pachydermatis fungemia has been reported in patients receiving
      parenteral nutrition. Biofilm formation on catheters may be related to the
      pathogenesis of this mycosis. We investigated the biofilm-forming ability of 12
      M. pachydermatis strains using a metabolic activity plate-based model and
      electronic microscopic evaluation of catheter surfaces. All M. pachydermatis
      strains developed biofilms but biofilm formation showed variability among the
      different strains unrelated to their clinical origin. This study demonstrates the
      ability of M. pachydermatis to adhere to and form biofilms on the surfaces of
      different materials, such as polystyrene and polyurethane.

PMID- 17510860
TI  - Candida albicans Als proteins mediate aggregation with bacteria and yeasts.
AB  - Candida albicans occupies a microniche on mucosal surfaces where diverse
      microbial populations interact within a biofilm. Because C. albicans is
      intimately involved with other microbes in this environment we studied the
      interactions of C. albicans with other fungi and bacteria that form mixed
      microbial aggregates. Once aggregation is initiated, aggregates form rapidly and
      incorporate fungal as well as bacterial cells. The fungus formed mixed microbial
      aggregates with homotypic cells (i.e., self to self, e.g., C. albicans or Als1p
      expressing yeast cells aggregating with cells bearing Als1p); with heterotypic
      cells (i.e., self to non-self, e.g., C. albicans or Alsp-expressing yeast cells
      aggregating with other Candida species); and with xenotypic cells (e.g., C.
      albicans or Alsp-expressing yeast cells forming aggregates with bacteria). When
      either of the C. albicans adhesins Als1p or Als5p was displayed on the surface of
      non-adherent Saccharomyces cerevisiae cells, the S. cerevisiae also mediated
      these mixed microbial interactions. Thus the Als adhesins are potentially
      important for the co-adhesion of mixed microbial communities in biofilms and on
      mucus surfaces.

PMID- 17510861
TI  - Deep fungal dermatitis in three inland bearded dragons (Pogona vitticeps) caused
      by the Chrysosporium anamorph of Nannizziopsis vriesii.
AB  - The Chrysosporium anamorph of Nannizziopsis vriesii (CANV), a keratinophilic
      fungus that naturally and experimentally causes severe and often fatal dermatitis
      in multiple reptile species, was isolated in pure culture from skin samples of
      three inland bearded dragons (Pogona vitticeps) with deep granulomatous
      dermatomycosis. The first animal presented with a focal maxillary swelling
      involving the skin and gingiva. This lizard died while undergoing itraconazole
      and topical miconazole therapy. The second presented with focally extensive
      discoloration and thickening of the skin of the ventrum and was euthanized after
      10 weeks of itraconazole therapy. A third lizard presented with hyperkeratotic
      exudative dermatitis on a markedly swollen forelimb. Amputation and itraconazole
      therapy resulted in a clinical cure. Histopathology of tissue biopsies in all
      cases demonstrated granulomatous dermatitis with intralesional hyphae
      morphologically consistent with those produced by the CANV. The second lizard
      also had granulomatous hepatitis with intralesional hyphae. Evidence in this
      report suggests that the CANV is the etiologic agent of an emerging condition in
      captive bearded dragons that has been called 'yellow fungus disease'.

PMID- 17510862
TI  - Clustering of invasive Aspergillus ustus eye infections in a tertiary care
      hospital: a molecular epidemiologic study of an uncommon species.
AB  - Aspergillus infections are being increasingly recognized as an important cause of
      morbidity and blindness. We report here the first cluster of Aspergillus ustus
      endophthalmitis cases which occurred in a large tertiary care hospital during the
      period October 2003 to June 2004. In three of the cases, the patients required
      enucleation following cataract surgery, while the fourth involved a fatal
      infection in a pediatric patient hospitalized for osteopetrosis. Patient charts
      from the four cases were reviewed retrospectively and indicated that
      postoperative signs of fungal endophthalmitis developed in the patients 1-11
      weeks after surgery. The molecular characterization of the isolates and their
      epidemiological relatedness were evaluated by Random Amplification of Polymorphic
      DNA (RAPD). A source investigation of this mini outbreak was performed by
      environmental sampling, but no isolates of A. ustus were recovered from these
      studies. All A. ustus strains isolated from three patients with fungal
      endophthalmitis had the same RAPD pattern suggesting a common source. The strain
      from the pediatric patient differed from the ophthalmic isolates in five
      electrophoretic loci. The latter was included solely as an outbreak, unrelated
      control to evaluate the discriminatory power of the molecular typing method
      employed in the analysis of the ophthalmic strains. These cases illustrate the
      potential for uncommon species like A. ustus to cause high morbidity and
      mortality in some clinical settings. Aspergillus ustus endophthalmitis is a
      serious and devastating complication of ocular surgery. It is unknown whether
      ongoing hospital construction may have contributed to this cluster of cases.
      Random amplification of polymorphic DNA may give valuable clues about the
      clonality of A. ustus strains.

PMID- 17510863
TI  - The results of late probing in congenital nasolacrimal duct obstruction.
AB  - PURPOSE: To evaluate the results of lacrimal probing in children at or older than
      1 year of age with congenital nasolacrimal duct obstruction. MATERIALS AND
      METHODS: Fifty eyes of 38 children (24 males, 14 females) with congenital
      epiphora who underwent nasolacrimal duct probing were evaluated in a prospective
      study. The age of the patients was between 12 and 101 months (mean: 33 months).
      Success of probing was defined as complete resolution of preoperative symptoms
      and signs. The mean follow-up was 8 months (3-28 months). RESULTS: The success
      rate of probing was 88% (44/50 eyes). Residual epiphora was observed in 6 eyes of
      4 patients (12%). Age of the patient, gender, the frequency of epiphora before
      probing and the unilaterality or bilaterality of epiphora did not correlate with
      the success of probing (p > 0.05). CONCLUSION: Nasolacrimal duct probing is
      advocated as a primary treatment in children younger than 9 years of age before
      proceeding to more complex treatment options. Unsuccessful probing may result
      from the selection of nonmembranous obstructions rather than the increased age of
      the patients.

PMID- 17510864
TI  - Comparison of three methods for the treatment of pterygium: amniotic membrane
      graft, conjunctival autograft and conjunctival autograft plus mitomycin C.
AB  - OBJECTIVE: To compare three techniques combined with excision in the treatment of
      primary and recurrent pterygium: amniotic membrane transplantation, conjunctival
      autograft, and conjunctival autograft plus mitomycin C. MATERIALS AND METHODS:
      Forty-nine eyes of 49 subjects (30 primary, 19 recurrent pterygium) were included
      in this study. Combined with excision, 25 eyes (18 primary, 7 recurrent
      pterygium) were treated with conjunctival autografts (Group 1), and 16 eyes (12
      primary, 4 recurrent pterygium) were treated with amniotic membrane
      transplantation for the closure of the defect (Group 2). In 8 eyes (all recurrent
      pterygium) low-dose mitomycin C (0.02%) was applied topically to the defect area
      and a conjunctival autograft was applied thereafter (Group 3). The three groups
      were compared with regard to the recurrence of pterygium and the defect area
      requiring treatment. RESULTS: The number and percentages of recurrence seen in
      groups 1, 2 and 3 were as follows: 4 (16%), 4 (25%), and 0(-), respectively. For
      the treatment of primary pterygium cases, amniotic membrane closure and
      conjunctival autograft closure were comparable in effectiveness (p > 0.05). In
      the treatment of recurrent pterygium, there was no significant difference between
      the three techniques (p > 0.05). Amniotic membrane closure and conjunctival
      autografts were equally effective for the treatment of both primary and recurrent
      pterygium (p > 0.05). The graft size was significantly larger in the cases with
      recurrent pterygium (p = 0.016). CONCLUSIONS: Amniotic membrane closure and
      conjunctival autografts seem to be equally effective in the prevention of
      recurrence of primary pterygium. Conjunctival autografts combined with mitomycin
      C are as effective as the above two techniques to prevent recurrence in the
      treatment of recurrent pterygium. Due to the larger area of subconjunctival
      fibrosis, a larger defect area is created after the excision of pterygium tissue
      and a larger graft is needed to close this defect in recurrent pterygium. This
      factor can guide the surgeon during the planning of the surgery to choose the
      most appropriate technique for closure of the defect.

PMID- 17510865
TI  - Snip punctoplasty offers little additive benefit to lower eyelid tightening in
      the treatment of pure lacrimal pump failure.
AB  - Lacrimal pump failure refers to epiphora due to reduced tear outflow in the
      presence of a patent lacrimal drainage system and well-positioned puncta. This
      condition has been managed with dacryocystorhinostomy and lower eyelid
      tightening, which carry success rates of 50-94% and 84-91%, respectively. In this
      retrospective study, 23 eyes with symptomatic epiphora attributed to lacrimal
      pump failure underwent the lateral tarsal strip procedure and lower eyelid snip
      punctoplasty, and 20 eyes (87%) experienced complete or nearly complete
      resolution of tearing. This success rate is quite similar to that of prior
      studies of eyelid tightening alone for lacrimal pump failure, suggesting that the
      addition of the snip punctoplasty may not offer any additional benefit in
      patients with little or no punctal stenosis. All patients displayed some degree
      of lower eyelid laxity on lid distraction testing preoperatively, and those with
      only mild lid laxity responded at least as well as those with more severe laxity.

PMID- 17510866
TI  - Evaluation of patient comfort with outpatient orbital surgery.
AB  - PURPOSE: To evaluate patient comfort with outpatient orbital surgery. DESIGN:
      Prospective, non-randomized study. METHODS: The experience of 34 consecutive
      outpatient orbital procedures in 30 patients was evaluated. The data obtained
      included subjective postoperative pain and discomfort at 3 time intervals
      (immediate, postoperative day 1 and 1 week) using a 100 mm visual analogue scale
      (VAS). Patients were also asked to rate the overall experience after one week of
      follow-up. RESULTS: The average pain and discomfort scores in the immediate
      postoperative period measured 13.95 and 12.61, respectively. Overnight scores of
      5.91 and 7.25 were determined for pain and discomfort, and at the one-week follow
      up these were 0.91 and 3.42, respectively. All 30 patients reported that they
      were "satisfied with their overall experience." The highest VAS score for pain at
      any time was 50. The highest VAS score for discomfort at any time was also 50.
      All 30 patients had recovered or improved their visual acuity at week one. There
      was no incidence of retrobulbar hemorrhage, significant loss of vision (greater
      than two lines), increased intraocular pressure or pupillary defects in any of
      the patients. None of the study patients required re-hospitalization.
      CONCLUSIONS: This study suggests that outpatient orbital surgery, in the hands of
      an experienced orbital surgeon, is safe and well tolerated by the patients
      regardless of the type of anesthesia or type of procedure.

PMID- 17510867
TI  - Treatment of the lower eyelid with the CO2 laser: transconjunctival or
      transcutaneous approach?
AB  - PURPOSE: To compare the effects of CO(2) laser transcutaneous blepharoplasty with
      CO(2) laser transconjunctival blepharoplasty with simultaneous resurfacing for
      the treatment of lower lid dermatochalasis. METHODS: Thirteen men and 23 women,
      between 42 and 67 years of age, participated in this study. Patients were divided
      into two groups: (1) CO(2) laser transconjunctival blepharoplasty with
      resurfacing or (2) CO(2) laser transcutaneous blepharoplasty by the skin-muscle
      approach without resurfacing. The two operative techniques were compared with
      regard to the patient's satisfaction, complications and effectiveness on lower
      lid bulging and wrinkles. RESULTS: Transconjunctival blepharoplasty with
      simultaneous laser resurfacing yielded satisfactory results with improvement of
      the lower lid bulging in 92% of the 20 subjects. Persistent erythema was seen in
      only 5% and hiperpigmentation in 10% of this group, but 80% of the patients
      complained of long postoperative care. On the other hand, with the transcutaneous
      approach, lower lid bulging was perfect in 98% of the 16 subjects; although the
      rate of complications such as lateral canthal rounding (3.2%) and ectropion
      (6.25%) was higher, the patients had no problems with the period of postoperative
      care. Fourteen of 16 subjects in this group also demonstrated a better appearance
      of the lower lid wrinkles. CONCLUSION: Although transconjunctival blepharoplasty
      with laser resurfacing is now the most common surgical procedure for lower eyelid
      dermatochalasis and orbital fat herniation, postoperative care after laser
      resurfacing can be a problem in a certain group of patients. Transcutaneous
      blepharoplasty via the skin-muscle approach may be preferable in certain cases
      because of the short recovery period.

PMID- 17510868
TI  - Epibulbar osseous choristoma: benign pathology simulating an intraorbital foreign
      body.
AB  - Epibulbar osseous choristomas typically present, in the young, as a supero
      temporal subconjunctival nodule and radiographic imaging often shows a densely
      radio-opaque fleck on the sclera--this often being misinterpreted as a parabulbar
      foreign body. Four illustrative cases are presented.

PMID- 17510869
TI  - Preseptal and orbital cellulitis in a developing country.
AB  - PURPOSE: To report the clinical features, etiology, management practices, and
      outcomes of preseptal (PC) and orbital cellulitis (OC) in a developing country.
      METHODS: The charts of all patients with PC and OC at the Philippine General
      Hospital from 1990 to 1995 were reviewed and the following data retrieved: age,
      gender, manner of presentation, causative agent, treatment, and outcomes.
      RESULTS: Of 91 patients, 56 (62%) were diagnosed with PC and 35 (38%) with OC.
      The mean age at presentation was 12.6 +/- 17.0 years and 17.1 +/- 18.6 years,
      respectively. No sex predilection was observed. Ophthalmoplegia, chemosis, pain,
      proptosis, and blurred vision were associated with OC. Eyelid infection was the
      most common antecedent factor and was present in 15 (27%) PC patients and 13
      (37%) OC patients. Staphylococcus was the most frequent causative organism.
      Intravenous antibiotics were administered to 35 (62%) PC patients and all
      patients with OC. Surgical intervention was performed in 15 (27%) PC patients and
      22 (63%) OC patients. None of the PC patients developed permanent sequelae.
      Seventeen (49%) OC patients developed serious complications such as: visual loss
      (29%), neurological deficits (17%), and mortality (3%). CONCLUSIONS: In
      developing countries, eyelid infection may be the most important predisposing
      factor for periocular infection. Staphylococcus is the predominant causative
      agent. OC can be associated with serious complications. Aggressive management of
      OC may improve patient outcomes.

PMID- 17510870
TI  - Periorbital tuberculosis.
AB  - An observational case series of seven cases of periorbital tuberculosis, a rare
      tubercular presentation occurring in patients with and without systemic disease,
      is presented. Non-healing sinus and osteomyelitis of periorbital flat bones was
      observed. All cases had a positive Monteaux test and PCR. AFB cultures of the
      sinus discharge were negative. The response to triple-drug therapy was dramatic.
      Follow-up at the end of one year showed clinical recovery. The authors stress the
      need for a high index of suspicion in cases of non-healing lesions and atypical
      inflammatory presentation in the periorbital region.

PMID- 17510871
TI  - A rare diagnosis of dedifferentiated liposarcoma of the orbit.
AB  - We report the case of a 56-year-old female who presented to the ophthalmic
      casualty department with proptosis and diplopia. Initially, non-specific orbital
      inflammation was suspected while investigations were ongoing. A trial of steroids
      failed to resolve the proptosis to a significant extent. A CT scan showed a well
      defined orbital mass, which on orbital biopsy was shown to be a primary orbital
      liposarcoma of the dedifferentiated variety. This was confirmed by expert
      histopathological analysis. An exenteration followed by removal of orbital bone
      was required to achieve total tumour removal. Radiotherapy was delivered to
      reduce the chance of micro-metastasis. Orbital liposarcoma is an extremely rare
      tumour. The dedifferentiated variety is even rarer, with only a few reported
      cases. Lack of information about this potentially aggressive tumour may create
      therapeutic dilemmas as to the best treatment approach. Similarly, prediction of
      an accurate prognosis for the patient may be difficult due to the rarity of this
      condition.

PMID- 17510872
TI  - Necrotizing pseudomonas blepharoconjunctivitis.

PMID- 17510873
TI  - An atypical case of Sjogren's syndrome causing unilateral severe lacrimal gland
      enlargement and hypoglobus.
AB  - We report the first case of Sjogren's syndrome causing gross lacrimal gland
      swelling and secondary hypoglobus and uncharacteristically absent sicca syndrome.
      Histopathological diagnosis of the excision biopsy of the orbital lobe of the
      gland confirmed a mixed T and B cell infiltrate of the gland with no lymphomatous
      transformation. The condition remains quiescent following complete excision.

PMID- 17510874
TI  - Bilateral actinomycotic blepharokeratoconjunctivitis.
AB  - Actinomycotic conjunctivitis is usually unilateral and secondary to
      canaliculitis. We report an unusual case of bilateral actinomycotic
      blepharokeratoconjunctivitis in the absence of canaliculitis. Keratitis occurred
      without any preceding ocular trauma. Both eyes had remissions and relapses in
      response to the antibiotic-steroid drops. Diagnosis of A. israelii infection was
      made on the basis of Gram staining, culture and biochemical characteristics.
      Complete excision of the conjunctival ulcer along with penicillin therapy
      resulted in cure. This case highlights that microorganisms of the order
      Actinomycetales should be considered in the differential diagnosis if
      conjunctivitis or keratitis shows a waxing and waning course.

PMID- 17510875
TI  - A non-invasive pigmented nodule arising within primary acquired melanosis--an
      unusual phenomenon.
AB  - We report a case of a raised pigmented nodule that arose within conjunctival
      primary acquired melanosis (PAM). This nodule showed no histological features of
      invasive disease.

PMID- 17510876
TI  - Retrobulbar cysticercosis masquerading as optic nerve glioma.
AB  - Extra ocular muscles are the most common site of involvement in orbital
      cysticercosis. We present a case of retrobulbar cysticercosis masquerading
      clinically as optic nerve glioma.

PMID- 17510877
TI  - Scleral MIRAgel causing bony orbital erosion.
AB  - The authors report a case of hydrogel scleral explant (MIRAgel) causing an
      incomitant strabismus, diplopia, enophthalmos and a dehiscence in the roof of the
      orbit secondary to pressure-related atrophy due to swelling of the explant
      occurring 10 years after its placement.

PMID- 17510878
TI  - Optochiasmal avulsion secondary to minor occipital trauma.
AB  - BACKGROUND: Optic nerve avulsion is an extremely rare occurrence and usually
      arises in the setting of severe fronto-orbital fractures or penetrating orbital
      injuries. However, a few cases have been associated with minor injury. OBJECTIVE:
      To overview the pathophysiology of delayed optochiasmal avulsion following minor
      ocipital trauma and discuss management options. METHODS: Report of a unique case
      of a 79-year-old woman who presented with delayed partial expulsion of the right
      globe and complete optic nerve avulsion following closed head injury to the
      occiput. CONCLUSION: Antero-posterior distortion of the skull following such a
      deceleration injury can cause laceration and thrombosis of the pre-chiasmal and
      pial arteries supplying the optic chiasm. The ensuing ischaemic changes
      subsequently caused delayed softening of the chiasm and its avulsion. The
      concomitant retrobulbar haemorrhage and mass effect within the orbit consequently
      led to the partial expulsion of the globe.

PMID- 17510879
TI  - Cystic orbital metastasis from endometrial carcinoma.
AB  - PURPOSE: To describe a rare orbital metastasis with atypical presentation. DESIGN
      AND METHODS: Retrospective case report. RESULTS: The patient presented with a
      rapid onset of a cystic orbital lesion after a presumptive diagnosis of
      endometrial carcinoma that had been completely excised eight months ago. This was
      the initial presentation of widespread metastasis. CONCLUSIONS: Endometrial
      carcinomas can metastasize to the orbit and may have a very atypical
      presentation.

PMID- 17510883
TI  - Solventless pharmaceutical coating processes: a review.
AB  - Coatings are an essential part in the formulation of pharmaceutical dosage form
      to achieve superior aesthetic quality (e.g., color, texture, mouth feel, and
      taste masking), physical and chemical protection for the drugs in the dosage
      forms, and modification of drug release characteristics. Most film coatings are
      applied as aqueous- or organic-based polymer solutions. Both organic and aqueous
      film coating bring their own disadvantages. Solventless coating technologies can
      overcome many of the disadvantages associated with the use of solvents (e.g.,
      solvent exposure, solvent disposal, and residual solvent in product) in
      pharmaceutical coating. Solventless processing reduces the overall cost by
      eliminating the tedious and expensive processes of solvent disposal/treatment. In
      addition, it can significantly reduce the processing time because there is no
      drying/evaporation step. These environment-friendly processes are performed
      without any heat in most cases (except hot-melt coating) and thus can provide an
      alternative technology to coat temperature-sensitive drugs. This review discusses
      and compares six solventless coating methods - compression coating, hot-melt
      coating, supercritical fluid spray coating, electrostatic coating, dry powder
      coating, and photocurable coating - that can be used to coat the pharmaceutical
      dosage forms.

PMID- 17510884
TI  - Influence of process parameters on pellets elaborated in a Mi-pro high-shear
      granulator.
AB  - The aim of the study was to prepare porous pellets several hundred micrometers in
      diameter into or onto which drug substances could be embedded. Wet granulation
      was carried out on a powder mix of alpha-lactose and polyvinylpyrrolidone in a Mi
      Pro high-shear granulator. The process parameters were investigated to point out
      their influence on pellet physical properties. The reference conditions of
      granulation that gave the most satisfactory pellets in size and shape were
      determined by adjusting the volume and the distribution rate of water. Increasing
      impeller speed resulted in an increase in granule size and granulation yield and
      in a decrease in proportion of fines. The granules showed easy flowing for all
      granulation conditions. Adjusting process parameters enabled control of size,
      shape, surface area, and porosity of the granules and thus the design of ready to
      use granules to which drug substances could be associated by deposition or
      inclusion.

PMID- 17510885
TI  - Effect of formulation and processing variables on the granulation kinetics of hot
      melt granulation (HMG) process.
AB  - The objective of the study was to evaluate the effect of formulation factors,
      such as type of drug and particulate properties of a drug, and processing
      variables, i.e. jacket temperature, impeller speed, and scale, on granulation
      kinetics the of hot-melt granulation (HMG) process. Two model active
      pharmaceutical ingredients (API) Ro-A and indomethacin were selected for this
      evaluation using poloxamer 188 as a meltable binder. The effect of solid-state
      properties of API was investigated for Ro-A, whereas the binder properties were
      maintained constant. General factorial design was used to investigate the effect
      of independent process variables, impeller speed and jacket temperature using
      impeller motor power consumption as response variable. Consistent granulation
      could be developed for Ro-A by optimizing the binder level and impeller speed,
      however, the addition of third excipient was necessary for indomethacin. The
      granulation rate was related to the bulk density and the surface area of the
      drug. The jacket temperature affected overall granulation time but had no
      significant effect on the granulation kinetics, suggesting that faster heating
      rate is desirable for optimal productivity. A significant increase in the
      granulation rate was observed with increase in impeller speed. The effect of
      impeller speed was further confirmed at 5 L and 25 L scale. From the formulation
      prospective, the critical factors were the level of binder, inherent binding
      properties of the API, the solid-state properties of API and binder. From
      processing perspectives, the impeller speed had a significant effect on the
      granulation kinetics.

PMID- 17510886
TI  - Influence of binder type on interacting variables acting on mechanical properties
      of a sulfadimidine tablet formulation.
AB  - A study of the quantitative effect of type of binder (N), applied pressure (P),
      and granular size (G) on two mechanical properties-tensile strength (TS) and
      brittle fracture index (BFI) - of a sulfadimidine tablet formulation has been
      carried out by using a 2(3) factorial experimental design. The results obtained
      from this work suggest that P exhibited the largest individual effect on TS and
      BFI. It is also seen from this work that the nature of binders in combination
      affects the influence that P and G had on the TS or BFI.

PMID- 17510887
TI  - Structural changes in xanthan gum solutions during steam sterilization for
      sterile preparations.
AB  - Steam sterilization of xanthan gum solutions at 121 degrees C caused a decrease
      in the helix conformation as well as the molecular weight distribution with a
      corresponding increase in the coil structure. The effect was directly related to
      the exposure time and inversely to the xanthan gum concentration, thus suggesting
      a two-step mechanism of disentanglement followed by degradation with the first
      step being predominant at higher concentrations. Mark-Houwink exponent of 0.9002
      for the intrinsic viscosity of xanthan gum compared favorably with reported
      values in the literature. The model for intrinsic viscosity of a free draining
      coil yielded an expansion coefficient of 1.2 (independent of molecular weight)
      and a root mean square radius of unperturbed chain in the range of 189.5-368 nm.
      The root mean square unperturbed chain length increased with molecular weight
      without reaching an asymptotic value, thus indicating that the xanthan molecule
      behaved as a stiff chain.

PMID- 17510888
TI  - Transdermal permeability of N-acetyl-D-glucosamine.
AB  - Transdermal permeation of N-acetyl-D-glucosamine (NAG), a metabolite of
      glucosamine was examined. Glucosamine salts are nutraceuticals used in the oral
      treatment of osteoarthritis. Sparse information is available regarding
      glucosamine and NAG transdermal or percutaneous transport and absorption.
      Permeability of NAG in various enhancer suspensions was evaluated by using shed
      snakeskin as a model membrane via Franz-type cell diffusion studies. Negligible
      permeability was observed for NAG in neat solutions of known membrane permeation
      enhancers ethanol, oleic acid, isopropyl myristate, and isopropyl palmitate, as
      well as from saturated solutions of NAG in water or phosphate buffer.
      Permeability measurements obtained from saturated solutions of NAG in DMSO and
      phosphate buffer solutions containing ethanol at 2%, 5%, 10%, 25%, and 50%
      demonstrated excellent permeation. Permeability coefficients of the phosphate
      buffer/ethanol solutions at 5%, 10%, and 25% were about threefold larger in value
      as those for saturated DMSO solution, whereas the 2% and 50% solution values were
      lower.

PMID- 17510889
TI  - Low-voltage electrohydrodynamic (EHD) spray drying of respirable particles.
AB  - Spray drying is a widely used process to produce pharmaceutical powders. In
      traditional spray drying, the particle size distribution is wide and not well
      controlled. Using EHD atomization for spray drying offers a possibility to tailor
      the particle size and morphology. In conventional EHD spray drying, the generated
      particles are charged and need to be discharged to avoid Rayleigh breakup.
      Discharging adds complexity to the process and eliminates the possibility to
      collect the powder using an electric field. The present work describes a novel
      EHD spray drying setup based on a low-voltage nozzle. The low-voltage nozzle
      imparts moderate charge to the droplets, which makes discharging unnecessary. The
      charged particles can be controlled and collected by using an auxiliary electric
      field. The EHD spray dryer has been characterized in terms of particle size,
      particle morphology, process output, and yield. The size distribution of the
      generated particles is very narrow. Both porous and completely spherical
      particles can be produced. The yield of small-scale bench-top equipment was 20%,
      which is similar to the yield of a small-scale conventional spray dryer. The
      effective output with five nozzles was 75 mg/hr of dry powder. Because of the
      repelling forces associated with the unipolarly charged droplets, the number of
      nozzles can be increased without risking coalescence.

PMID- 17510890
TI  - Novel potential drug against T. cruzi and its interaction with surfactant
      micelles.
AB  - The interaction of 5-nitro-2-furfurilylidene benzhydrazide (5NFB), potential anti
      trypanosomal compound, with micellar solutions was studied. The results indicated
      that 50 mug of 5NFB completely kills 20 million T. cruzi epimastigote cells
      within 3 days, whereas the same amount of benznidazole kills 30% of the cells
      after 4 days. 5NFB solubility in surfactants solutions (SDS, DTAB, C12EO8)
      increased linearly with surfactant concentration. According to small angle X-ray
      scattering (SAXS), 5NFB does not affect micellar structural features. A
      comparison between C12EO8 effects on T. cruzi epimastigote cells and on
      erythrocytes showed that surfactant lytic effect is stronger in parasite cells,
      enlightening the potential of 5NFB micellar formulations.

PMID- 17510891
TI  - Pharmacokinetic modeling and simulation of gastrointestinal transit effects on
      plasma concentrations of drugs from mixed immediate-release and enteric-coated
      pellet formulations.
AB  - Effects of gastrointestinal transit on plasma concentrations of drugs from mixed
      immediate-release and enteric-coated pellet formulation were simulated with
      models developed by including gastric emptying time and lag time of emptying.
      Models were evaluated by comparing simulated plasma concentrations of amphetamine
      from Monte Carlo simulations to available published data of a commercial mixed
      pellet formulation (Adderall XR). Results show that the plasma profile from the
      mixed pellet formulation does not mimic that from two immediate-release doses
      administered at different times. Instead, the plasma profile from the mixed
      pellets of amphetamine is similar to a typical sustained-release formulation. The
      pharmacokinetic models presented herein describe plasma concentrations of
      amphetamine from mixed pellet formulation quite well. The models and assumptions
      are general and can be applied to other drugs in similar mixed pellet dosage
      forms.

PMID- 17510892
TI  - Characterization of 5-fluorouracil release from hydroxypropylmethylcellulose
      compression-coated tablets.
AB  - Hydrogel compression-coated tablets are able to release the core drug after a
      period of lag time and have potential for colon-specific drug delivery based on
      gastrointestinal transit time concept. This study investigated the factors
      influencing in vitro release characteristics of a model drug 5-fluorouracil from
      hydroxypropylmethycellulose (HPMC) compression-coated tablets. The core tablet,
      prepared by a wet granulation compression method, was designed to disintegrate
      and dissolute quickly. To prepare the compression-coated tablets, 50% of the
      HPMC/lactose coat powder was precompressed first, followed by centering the core
      tablet and compressing with the other 50% of the coat powder. Release
      characteristics were evaluated in distilled water by using a Chinese
      Pharmacopoeia rotatable basket method. Effect of HPMC viscosity, lactose content
      in outer shell, and overall coating weight of outer shell on release lag time
      (T(lag)), and zero-order release rate (k) were studied. Release of drug from
      compression-coated tablets began after a time delay as a result of hydrogel
      swelling/retarding effect, followed by zero-order release for most of the
      formulations studied. HPMC of higher viscosity (K4M and K15M) provided better
      protection of the drug-containing core, showing increased release lag time and
      slower release rate. Incorporating lactose in outer shell led to decrease of
      T(lag) and increase of k. T(lag) and k are exponentially and linearly correlated
      to lactose content, expressed as weight percentage of the outer shell. Larger
      coating weight (W) of outer shell produced larger coating thickness (D) around
      core tablet, which resulted in increase in T(lag) and decrease in k. There was
      good fitting of a linear model for each of the four variables W, D, T(lag), and
      k. Hardness of the compression-coated tablets and pHs of the release media had
      little effect on drug release profile. It is concluded that the release lag time
      and release rate are able to be tailored through adjusting the formulation
      variables to achieve colon-specific drug delivery of 5-fluorouracil.

PMID- 17510893
TI  - Interaction of moisture with sodium starch glycolate.
AB  - The relationship between the apparent moisture content and moisture sorption of
      modified starches was investigated. Samples of sodium starch glycolate (SSG),
      pregelatinized starch (PGS) and potato starch (PS) were stored for various times
      at 44% or 75% relative humidity (RH) to produce samples with moisture contents of
      up to 14%, as determined by loss on drying (LOD). Evaluation of LOD and mass gain
      data suggested that measured mass gain equated to predicted LOD values for PGS
      and PS. However, in SSG there was a nonstoichiometric relationship between mass
      gain and predicted LOD. In addition, samples of SSG displayed hysteresis during
      dynamic vapor sorption (DVS) cycling in that an apparent mass loss of about 2-3%
      was observed for two of the SSGs, with PS and PGS exhibiting reversibility. In
      some cases, SSG exhibited an apparent mass loss during the DVS cycle at with 50%
      RH. These observations suggest that one or more of the components of SSG
      "interact" with moisture. Because X-ray diffraction suggested there was no
      dramatic change in the crystallinity of SSG, an exchange of residual SSG solvent,
      alcohol, with moisture may, in part, explain the moisture sorption behavior of
      SSG.

PMID- 17510894
TI  - Effect of moisture on the compressibility and compactibility of sodium starch
      glycolate.
AB  - The relationship between the apparent moisture content and compactibility of
      sodium starch glycolate was compared to similarly obtained data for
      pregelatinized starch. Samples of sodium starch glycolate (SSG) and
      pregelatinised starch (PGS) were stored at 44% or 75% relative humidity (RH),
      producing samples exhibiting moisture contents of up to 14% w/w, as determined by
      loss on drying (LOD). Increasing the moisture content of SSG and PGS resulted in
      an increase in compressibility and compactibility for both materials. However,
      the effect was more dramatic for SSG with unlubricated compactibilities of 2.0
      MPa and 0.9 MPa at approximately 11.5% LOD for SSG and PGS, respectively, which
      was further exemplified in the compactibility of lubricated materials and in
      blends with microcrystalline cellulose. These results suggested that moisture
      content had a greater effect on the compactibility of SSG compared with PGS and
      that the interactions of water with the components of the SSG starch granules may
      be different from those within the PGS starch granules at comparable LOD values.

PMID- 17510895
TI  - Generic health-related quality of life amongst patients employing different voice
      restoration methods following total laryngectomy.
AB  - Three methods of voice restoration--tracheosophageal speech (TEP), oesophageal
      speech, electrolarynx--are available following total laryngectomy. TEP produces
      better voice quality compared with other methods and is assumed to result in
      better quality of life. Little evidence exists to support the relationship
      between voice quality and quality of life, however. Advertising this study
      through several leading laryngectomy charities resulted in the completion of 226
      questionnaires (TEP = 147; oesophageal speech = 42; electrolarynx = 37)
      comprising the Short Form 36 (SF-36) quality of life measure and questions
      examining perceived voice intelligibility. Additionally, 89 questionnaires
      comprising only the SF-36 were completed by participants who reported having no
      serious medical problems, to form a healthy control group. Results indicate that
      improved voice quality does not result in widespread benefits to quality of life.
      On only a few dimensions were there differences between voice restoration method:
      electrolarynx and TEP better than oesophageal speech with respect to pain, TEP
      better than oesophageal speech with respect to role limitation: physical
      problems. Additionally whilst widespread differences between voice restoration
      methods did not occur, all three groups had a worse quality of life compared with
      the healthy control group. Implications of the results for the selection of voice
      restoration method to maximize quality of life are discussed.

PMID- 17510896
TI  - Application of a stress and coping model to antenatal depressive symptomatology.
AB  - This study examined the utility of a stress/coping model of antenatal depressive
      symptomatology. The direct and moderating effects of appraisal, coping resources
      and coping strategies on depression were explored. A total of 242 primiparous
      women completed questionnaires during the third trimester of pregnancy.
      Predictors included life events, coping resources (social support, quality of
      women's earlier relationships with parents), appraisal (threat, self-efficacy)
      and coping strategies (wishful thinking, positive reappraisal, problem solving,
      emotional approach). Results of regression analyses indicated that higher
      depression was related to higher stressful life events, threat appraisal and
      wishful thinking coping, and lower positive reappraisal coping. The expected
      stress exacerbation effects of wishful thinking on depression were supported.
      There was no support for the expected stress buffering effects of coping
      resources and coping strategies on depression. Findings provide preliminary
      support for the use of a stress/coping model to guide future research into
      psychosocial predictors of antenatal depression.

PMID- 17510897
TI  - How do women experience myocardial infarction? A qualitative exploration of
      illness perceptions, adjustment and coping.
AB  - While UK Department of Health policy recognizes the importance of secondary
      prevention and rehabilitation following a cardiac event, there still appears a
      dearth of research addressing women's needs. This study aimed to explore
      adjustment in terms of women's perception of their cardiac event, impact on
      relationships and coping strategies employed. Five women suffering first time MI
      were interviewed, using a semi-structured format and were telephoned 2 months
      later. Data were analysed using Interpretative Phenomenological Analysis.
      Perceptions included: Making Sense of the Event, Cognitive and Emotional
      Responses and Self-beliefs. Relationships issues were: Others' Reactions and
      Change in Relationships and Roles. Cognitive and Behavioural strategies and
      Support from others (including cardiac rehabilitation) formed coping strategies.
      For most participants, the event was unexpected evoking uncertainty and later,
      emotions extending beyond the more widely accepted depression and anxiety. Women
      tended to minimize severity of symptoms and impact of event (perhaps as a way of
      coping and protecting others), displaying a strong sense of optimism and hope
      that life would soon return to "normal". However, it appeared this was difficult
      to maintain and the experience seemed to challenge relationships and roles. The
      findings suggest recommendations for further research with possible implications
      for clinical practice.

PMID- 17510898
TI  - Efficacy of a program to encourage walking in VA elderly primary care patients:
      the role of pain.
AB  - Pain may be a barrier or a negative outcome of initiating and maintaining an
      exercise program in elderly patients. The purpose of this study was to examine
      the role of pain in a program designed to increase walking for exercise in 181
      veteran primary care patients (60 - 80 years). Self-reported physical activity
      (min-walked per week) and pain were assessed at baseline, 6, and 12 months.
      Walking for exercise increased over time without significant changes in pain.
      Analyses suggested that baseline pain was not a barrier to initiating or
      maintaining a walking exercise program, nor did increased walking influence
      reports of pain. These results suggest that patients can be encouraged to engage
      in physical activity, even if they are currently suffering from pain.

PMID- 17510899
TI  - A cross-cultural study of psychosocial aspects of sickle cell disease in the UK
      and Nigeria.
AB  - Pain experience, health service utilization and psychological coping in adult
      patients with sickle cell disease were compared cross-culturally between the UK
      and Nigeria. Patients in the UK experienced a significantly greater number of
      pain episodes and of longer duration, with more frequent visits to accident and
      emergency departments compared with those in Nigeria. The Nigerian patients, on
      the other hand, applied more psychologically active coping strategies such as
      distraction to deal with their sickle cell pain in the community. These
      significant differences are explained in relation to external health locus of
      control factors including beliefs, and the cost of healthcare in relation to the
      use of health services. Clinical implications of these findings are also
      considered.

PMID- 17510900
TI  - Fatigue, cognitive functioning and psychological distress in Marfan syndrome, a
      pilot study.
AB  - Marfan patients report fatigue as a major subjective complaint. We found no
      studies exploring the subject. The aim of this study was in a strictly defined
      Marfan population to assess self-reported fatigue, cognitive functions and
      psychological distress, correlations among them and correlations to visual
      acuity, joint hypermobility and use of beta-blockers. Sixteen subjects aged 18 -
      30 years, fulfilling the Gent criteria, were assessed with the Fatigue Severity
      Scale, Fatigue Questionnaire, a comprehensive battery of neuropsychological tests
      and the General Health Questionnaire (GHQ). Self-reported fatigue was comparable
      with fatigue reported in other severe chronic diseases and disabilities, and was
      primarily in the mental/psychological domain. Psychological distress was higher
      than expected compared with the population at large. All neuropsychological test
      results were within the normal range, except for tests of visuo-motor
      coordination and speed of information processing. There was a significant inverse
      correlation between Fatigue Questionnaire ratings and some neuropsychological
      tests. Fatigue seems to be a serious problem for persons with Marfan syndrome and
      seems related to some areas of cognitive functioning. We found no overall
      impairment in cognitive functioning, but slightly reduced speed of information
      processing. Reduced visuo-motor coordination could be explained by impaired
      visual acuity.

PMID- 17510901
TI  - Use of traditional medicine by HIV-infected individuals in South Africa in the
      era of antiretroviral therapy.
AB  - As antiretroviral therapy (ART) becomes more available in African countries, the
      potential for interaction with traditional medicines becomes more important. We
      carried out a cross-sectional survey among individuals with moderate or advanced
      HIV disease attending a workplace clinic providing ART in South Africa to
      determine prevalence of traditional medicine use, source, recommended products
      and costs. Among 44 clinic attendees (100% male, median age 42 years, 30 taking
      ART), 37 (84%) reported ever using traditional medicines, 25 obtained from a
      healer or herbalist, eight from their own fields and four from a pharmacy.
      Fourteen of the 44 (32%) were currently using traditional medicines, most
      frequently African potato (9/14) and Aloe vera (3/14). Seven out of 30 persons
      taking ART (23%) reported currently using traditional medicines. Participants
      spent 4 - 27 pounds per month on traditional medicines. Traditional medicine use
      is common among individuals with moderate and advanced HIV disease. Concomitant
      use with ART has the potential for drug interactions and should be discussed
      routinely in ART counselling. Further work is warranted to investigate whether
      commonly used traditional medicines interact with ART in vivo.

PMID- 17510902
TI  - Effects of diets and their role in weight control.
AB  - This study examines the secondary effects of hypocaloric diets. The results show
      that the positive short-term effects with regards health are not maintained in
      the long term, as most people eventually return to their original weight. A
      description is given of how psychological reasons are more important than
      biological mechanisms when explaining this failure and stress is put on how
      carrying out successive hypocaloric diets can result in a subgroup of people
      becoming overweight or obese. Furthermore, an analysis is made of the
      relationship between diets, eating disorders and the "yo-yo effect", which is in
      turn associated with a rise in morbimortality due to a wide range of causes. As
      an alternative to the indiscriminate use of hypocaloric diets, a strategy based
      on the modification of lifestyle is suggested in order to control weight and
      improve health.

PMID- 17510903
TI  - Personality: a vulnerability factor in rhinitis?
AB  - Personality traits were assessed in 63 patients with persistent allergic or non
      allergic rhinitis with the Karolinska Scales of Personality, developed with the
      aim of measuring psychobiological vulnerability factors, and were compared with a
      reference group comprising a random sample of 400 sex- and age-stratified
      subjects. The patients' personality profile differed slightly - within one
      standard deviation - but significantly from the reference group on a number of
      factors together suggestive of a disinhibitory disposition, an inclination to
      express anxiety through somatic rather than psychological channels, difficulties
      in maintaining emotional distance to others, and a limited awareness of
      aggressive affect, a pattern that suggests that they expose themselves to more
      stimulation than they can process in terms of thought and feelings, generating
      sustained physiological arousal that may contribute to the development of their
      intolerance reactions.

PMID- 17510904
TI  - Satisfaction with care among low-income female outpatients.
AB  - Patient satisfaction correlates with important health behaviors and outcomes.
      Little is known about satisfaction in disadvantaged populations of different
      racial/ethnic backgrounds. The current study evaluated demographic and
      psychological correlates of patient satisfaction among a low-income, multiethnic
      sample of female outpatients attending cervical cancer screening. Participants
      included 338 African American, Latina, and white women ages 18 - 49 years
      attending University of Texas Medical Branch Regional Maternal & Child Health
      Clinics. Data were obtained via self-report and chart review. Patient
      satisfaction was assessed using the Patient Satisfaction Questionnaire (PSQ).
      Total PSQ scores reflected two distinct underlying subscales (satisfaction and
      dissatisfaction), which differed from the original factor structure of the PSQ.
      Satisfaction was predicted by patient beliefs that their health is self
      determined, beliefs that doctors control their health, self-esteem, and
      education. Dissatisfaction was predicted by patient beliefs that good health is a
      matter of chance/luck, self-esteem, social desirability, and income. Higher self
      esteem, education, and beliefs that health is controlled by oneself or doctors
      correlated with higher satisfaction with care in the clinic setting.
      Understanding the influence of patient characteristics on perceptions of care is
      important for physicians to foster relationships with patients that increase
      feelings of satisfaction, decrease dissatisfaction, and ultimately, improve
      health outcomes.

PMID- 17510905
TI  - Further validation of the Maudsley Marital Questionnaire (MMQ).
AB  - This study examined the Factor structure and internal consistency of the Dutch
      version of the Maudsley Marital Questionnaire (MMQ) for a sample of 787
      respondents in Belgium. Principal components analysis, followed by varimax
      orthogonal rotation, identified the expected three factors (M - Marital, S -
      Sexual, GL - General Life), which jointly explained 53% of the variance. The
      Cronbach alpha for MMQ - M (.90) and MMQ - S (.80) were of high value while for
      MMQ - GL (.66) was lower. The MMQ scales were found significantly correlated with
      each other: M - S, .60; M - GL, .46 and S - GL, .33.

PMID- 17510906
TI  - Physical activity and psychological well-being in children with Type 1 diabetes.
AB  - Physical activity and psychological well-being contribute to positive lifestyle
      and well-being in youngsters who have Type 1 diabetes. The aims of this study
      were to objectively assess the physical activity levels of children with Type 1
      diabetes, and investigate associations between physical activity levels,
      psychological well-being and HbA(1c). Thirty-six children, mean age 12.8 years,
      participated in the investigation. Physical activity was assessed using heart
      rate monitoring over four days. Children further completed the Diabetes Quality
      of Life for Youths Questionnaire, the Physical Self-Perception Profile for
      Children and the Self-Efficacy for Diabetes Scale. Routine outpatient HbA(1c)
      measurements were recorded. There were no significant associations between
      psychological well-being and physical activity, or HbA(1c) and physical activity,
      thus suggesting physical activity does not directly relate to psychological well
      being in children with Type 1 diabetes. It may be that the effect of physical
      activity differs from that in children without Type 1 diabetes because of the
      place of physical activity within diabetes management and the need to balance
      this with insulin dosage and dietary intake to maintain blood glucose levels.

PMID- 17510907
TI  - A comparison of general and illness-related locus of control in Russians, ethnic
      German migrants and Germans.
AB  - General and illness-related locus of control play an immensely important role in
      the adherence and cooperation of patients in their therapy. Until now, culture
      specific aspects of these subjective theories have rarely been investigated.
      However, in view of the growing proportion of migrants in the German population,
      they are becoming increasingly significant. In a project supported by the
      Volkswagenstiftung (Volkswagen Foundation), a total of 607 healthy people were
      surveyed. The sample includes 307 ethnic German migrants from the successor
      states of the former Soviet Union (descendents of German origin who had emigrated
      to Russia during the 18th and 19th centuries) and 300 native Russians in Russia.
      They were compared with 100 Germans (matched from a previous study). The data
      were collected using questionnaires entitled "Multidimensional Health Locus of
      Control (MHLC)" and "Illness-related Locus of Control". The ethnic German
      migrants differed from the Russian sample in their health beliefs and attitudes
      towards medicine. However, in the first 18 months after migration, hardly any
      changes were observed. Fatalistic factors played only a minor role. Locus of
      health control was associated with beliefs about recovery from myocardial
      infarcts and tumours. Socio-demographic variables were of varying significance in
      the individual cultures. Gender influences on health beliefs were different in
      the subsamples. The level of education had only a minor influence on health
      attitudes. For those individuals who were acquainted with an ill person, internal
      factors in treatment of myocardial infarct and external psychosocial factors in
      cure of cancer played a larger role.

PMID- 17510908
TI  - Why don't health professionals check patient understanding? A questionnaire-based
      study.
AB  - Checking patient understanding, by asking questions about information presented
      in a medical consultation, is a core communication skill but its use is not
      frequently assessed. The newborn hearing screening commenced in England with a
      pilot of its implementation in January 2002. Because it is a new screening test,
      it provided an opportunity for studying the effective communication of novel
      information. A randomized controlled trial of training newborn hearing screeners
      to present information about the screening test and to ask questions to check
      understanding was commenced but had to be prematurely ended as the majority of
      the screeners did not ask the questions. The aim of this study was to understand
      why the screeners did not ask questions to check understanding of the information
      provided. Questionnaires were sent to screeners who participated in the study to
      elicit their responses to the use of the questions to check understanding. A
      response rate of 87% (26/30) was achieved. Screeners who reported not asking the
      questions were more likely to express a lack of confidence in their ability to
      ask questions, and to perceive asking questions as an ineffective way of
      increasing patient understanding. The study suggests that the ability and
      willingness of healthcare professionals to use simple communication skills may
      have been overestimated and training needs to target skills as well as beliefs
      about the effectiveness of using them.

PMID- 17510911
TI  - Clinical, biochemical and molecular aspects of cerebellar ataxia and Coenzyme Q10
      deficiency.
AB  - Coenzyme Q(10) (CoQ) deficiency is an autosomal recessive disorder presenting
      five phenotypes: a myopathic form, a severe infantile neurological syndrome
      associated with nephritic syndrome, an ataxic variant, Leigh syndrome and a pure
      myopathic form. The third is the most common phenotype related with CoQ
      deficiency and it will be the focus of this review. This new syndrome presents
      muscle CoQ deficiency associated with cerebellar ataxia and cerebellar atrophy as
      the main neurological signs. Biochemically, the hallmark of CoQ deficiency
      syndrome is a decreased CoQ concentration in muscle and/or fibroblasts. There is
      no molecular evidence of the enzyme or gene involved in primary CoQ deficiencies
      associated with cerebellar ataxia, although recently a family has been reported
      with mutations at COQ2 gene who present a distinct phenotype. Patients with
      primary CoQ deficiency may benefit from CoQ supplementation, although the
      clinical response to this therapy varies even among patients with similar
      phenotypes. Some present an excellent response to CoQ while others show only a
      partial improvement of some symptoms and signs. CoQ deficiency is the
      mitochondrial encephalomyopathy with the best clinical response to CoQ
      supplementation, highlighting the importance of an early identification of this
      disorder.

PMID- 17510910
TI  - Transcriptional malfunctioning of heat shock protein gene expression in
      spinocerebellar ataxias.
AB  - Among the various dominantly-inherited spinocerebellar ataxias (SCAs), at least
      seven of them belong to the polyglutamine disease group and are caused by
      glutamine-coding CAG triplet repeat expansion. The expanded coding CAG repeat
      translates into a polyglutamine stretch in the disease protein, which leads to
      late-onset and progressive neurodegeneration. Expanded polyglutamine adopts a
      misfolded protein conformation, and is itself a cellular stressor which induces
      robust heat shock response (HSR). Under polyglutamine stress, heat shock proteins
      (Hsps) are produced in neurons to assist refolding and/or promote the degradation
      of misfolded proteins. Along with the progressive nature of polyglutamine
      degeneration, a gradual decline of HSR in degenerating neurons was observed. Such
      kind of reduction can be observed in a large family of hsp gene expression,
      including hsp22, 26, 27, and 70. This underscores an intimate relationship
      between the inducibility of hsp gene expression and the disease progression. In
      this review, we describe the current understandings of hsp gene dysregulation in
      polyglutamine disease.

PMID- 17510912
TI  - Subcellular regulation of metabotropic GABA receptors in the developing
      cerebellum.
AB  - Our understanding of GABAergic and glutamatergic neurotransmission in the CNS has
      been greatly influenced with the discovery and subsequent investigations of the
      metabotropic gamma-aminobutyric acid (B) (GABA(B)) receptors. These G-protein
      coupled receptors mediate slow inhibitory neurotransmission and are widely
      expressed and distributed in the cerebellum, where they play critical roles in
      neuronal excitability and modulation of synaptic neurotransmission. Their
      function is modulated by interaction with effector ion channels, notably inwardly
      rectifying K(+) channels and voltage-gated Ca(2+) channels. The receptors are
      encoded by two distinct subunits, GABA(B1) and GABA(B2), both of which are
      required in order to function normally in vivo, as shown in recombinant
      expression systems and in GABA(B1) -/- mice. The GABA(B1) and GABA(B2) subunits
      exhibit overlapping distributions in the cerebellar cortex, both at pre- and
      postsynaptic sites, during development and adulthood. They are in particular
      abundant in Purkinje cells prior to synaptogenesis and throughout postnatal
      development. Using high-resolution immunohistochemical techniques at the electron
      microscopic level in combination with quantitative analysis and three-dimensional
      reconstructions, it has recently been demonstrated that GABA(B) receptors undergo
      changes in localization on the surface of Purkinje cell dendrites and spines
      during postnatal development in association with the establishment and maturation
      of excitatory synapses. Due to this dynamic regulation, the highest densities of
      GABA(B1) and GABA(B2) subunits occur around the glutamatergic synapses between
      Purkinje cell spines and parallel fibre varicosities. This review highlights
      recent studies that have shed further light on the subcellular localization
      during postnatal development and the cell surface dynamics of GABA(B) receptors.

PMID- 17510914
TI  - The Croonian Lectures On The Clinical Symptoms Of Cerebellar Disease And Their
      Interpretation. Lecture I. 1922.

PMID- 17510913
TI  - Fructose metabolism in the cerebellum.
AB  - Under normal physiological conditions, the brain utilizes only a small number of
      carbon sources for energy. Recently, there is growing molecular and biochemical
      evidence that other carbon sources, including fructose, may play a role in neuro
      energetics. Fructose is the number one commercial sweetener in Western
      civilization with large amounts of fructose being toxic, yet fructose metabolism
      remains relatively poorly characterized. Fructose is purportedly metabolized via
      either of two pathways, the fructose-1-phosphate pathway and/or the fructose-6
      phosphate pathway. Many early metabolic studies could not clearly discriminate
      which of these two pathways predominates, nor could they distinguish which cell
      types in various tissues are capable of fructose metabolism. In addition, the
      lack of good physiological models, the diet-induced changes in gene expression in
      many tissues, the involvement of multiple genes in multiple pathways involved in
      fructose metabolism, and the lack of characterization of some genes involved in
      fructose metabolism have complicated our understanding of the physiological role
      of fructose in neuro-energetics. A recent neuro-metabolism study of the
      cerebellum demonstrated fructose metabolism and co-expression of the genes
      specific for the fructose 1-phosphate pathway, GLUT5 (glut5) and ketohexokinase
      (khk), in Purkinje cells suggesting this as an active pathway in specific
      neurons? Meanwhile, concern over the rapid increase in dietary fructose,
      particularly among children, has increased awareness about how fructose is
      metabolized in vivo and what effects a high fructose diet might have. In this
      regard, establishment of cellular and molecular studies and physiological
      characterization of the important and/or deleterious roles fructose plays in the
      brain is critical. This review will discuss the status of fructose metabolism in
      the brain with special reference to the cerebellum and the physiological roles of
      the different pathways.

PMID- 17510915
TI  - Relationship of abdominal obesity measured by DXA and waist circumference with
      insulin sensitivity in Hispanic and non-Hispanic white individuals: the San Luis
      Valley Diabetes Study.
AB  - BACKGROUND: To determine if dual-energy X-ray absorptiometry (DXA) measures of
      trunk fat, a user-defined abdominal region of interest (ROI) and waist
      circumference (WC) differ in their association with insulin sensitivity among
      Hispanics and non-Hispanic whites (NHW) or explain any ethnic differences in
      insulin sensitivity. METHODS: A cross-sectional study of data collected (1997-98)
      as part of the longitudinal San Luis Valley Diabetes Study was utilized. There
      were 664 non-diabetic participants including 349 women (220 NHW, 139 Hispanic)
      and 305 men (197 NHW, 108 Hispanic), average age 63 years. Measurements included
      body mass index, WC and DXA measures of total and abdominal fat. Fasting glucose
      and insulin were used to estimate insulin sensitivity using the QUICKI index. A 2
      h oral glucose tolerance test was used to classify participants with normal
      glucose tolerance (NGT) or impaired glucose tolerance (IGT). RESULTS: Among women
      with NGT, Hispanics had lower insulin sensitivity, with DXA trunk fat explaining
      the most variance in QUICKI and 54% of the ethnic difference in QUICKI after
      adjusting for total body fat and lean mass. Among men with NGT, there were no
      differences between Hispanics and NHW in insulin sensitivity or any differences
      in the association of the abdominal fat measures with insulin sensitivity. Among
      men and women with IGT, the fat distribution variables explained little variance
      in QUICKI. CONCLUSIONS: DXA measures of trunk fat provide additional information
      over WC and the DXA abdominal ROI measure about ethnic differences in insulin
      sensitivity between older Hispanic and NHW women with NGT.

PMID- 17510916
TI  - Quantitative polymerase chain reaction as a reliable method to determine
      functional lentiviral titer after ex vivo gene transfer in human mesenchymal stem
      cells.
AB  - BACKGROUND: Human mesenchymal stem cells (hMSCs) are a promising target for ex
      vivo gene therapy and lentiviruses are excellent gene transfer vehicles in hMSCs
      since they achieve high transduction rates with long-term gene expression.
      Nevertheless, senescence of hMSCs may limit therapeutic applications due to time
      consuming cell selection and viral titration. Here, we describe a fast and
      reliable method to determine functional lentiviral titer by quantitative
      polymerase chain reaction (qPCR) after highly efficient ex vivo gene transfer in
      hMSCs. METHODS: Lentivirus production was tested with different types of
      packaging systems. Using p24 ELISA remaining viral particles were detected in the
      cell culture supernatant. The lentiviral gene transfer efficiency was quantified
      by FACS analysis. Lentiviral titers were determined by qPCR of expressed
      transgenes. RESULTS: Third-generation self-inactivating vectors showed highly
      efficient gene transfer in hMSCs. No viral antigen was detected in the cell
      culture supernatant after four media changes, suggesting the absence of
      infectious particles after 4 days. We observed a linear correlation between virus
      dilution and level of transgene expression by qPCR analysis, therefore allowing
      viral titering by quantification of transgene expression. Finally, we
      demonstrated that transduced hMSCs retained their stem cell character by
      differentiation towards adipogenic, osteogenic and chondrogenic lineages.
      CONCLUSIONS: Quantification of transgene copy numbers by qPCR is a fast and
      reliable method to determine functional lentiviral titer after ex vivo gene
      transfer in hMSCs.

PMID- 17510917
TI  - G-CSF-lentivirus administration in rats provided sustained elevated neutrophil
      counts and subsequent EPO-lentivirus administration increased hematocrits.
AB  - BACKGROUND: Towards gene therapy treatment of patients with neutropenia,
      characterized by neutrophil counts < 500 cells/microl, we investigated the
      ability of lentivirus vectors to provide sustained granulocyte colony-stimulating
      factor (G-CSF) delivery and to permit transgene expression from a second virus
      administration in a preclinical rat model. METHODS: Rats were injected
      intramuscularly (IM) with 24 x 10(6) and 9 x 10(6) infectious units (IU) of a VSV
      G-pseudotyped self-inactivating (SIN) lentivirus encoding rat G-CSF cDNA and
      containing cPPT and PRE elements. To determine the effectiveness of a second
      virus administration treated rats and a naive rat received erythropoietin (EPO)
      lentivirus IM. Rats were monitored for neutrophil and red blood cell production.
      Lentivirus antibodies were assayed by virus-neutralizing assay and ELISA.
      RESULTS: High and low dose virus administration increased neutrophil counts to
      5660 +/- 930 cells/microl (mean +/- SD) and 4010 +/- 850 cells/microl,
      respectively, that were sustained for > 17 months and were significantly higher
      than controls counts of 1890 +/- 570 cells/microl (p< or =0.0002). Rats treated
      with EPO-virus produced significantly increased hematocrits (HCT) (63.1 +/- 4.3%
      vs. 46.0 +/- 3.2%, p < 0.0001) without effect on G-CSF-virus-mediated neutrophil
      production. Antivirus antibodies were not detectable at serum dilutions > or
      =1:10 by virus neutralization or ELISA. Lymphocytes and platelets were not
      significantly different between control and treated animals (p > 0.1). Only
      genomic DNA from muscle at injection sites was positive for provirus suggesting
      lack of virus spread. CONCLUSIONS: G-CSF-lentivirus administered IM provided
      elevated, sustained neutrophil counts that were unchanged by subsequent EPO
      lentivirus administration. Significantly increased hematocrits were obtained
      following EPO-lentivirus delivery. These data support the treatment of patients
      with severe chronic neutropenia by dosed lentivirus delivery IM.

PMID- 17510918
TI  - Myxoid/round cell and pleomorphic liposarcomas: prognostic factors and survival
      in a series of patients treated at a single institution.
AB  - BACKGROUND: The objective of this study was to investigate prognostic factors and
      clinical outcome of myxoid/round cell and pleomorphic liposarcoma. METHODS: Three
      hundred twenty-nine patients with localized myxoid/round cell or pleomorphic
      liposarcoma who underwent surgery at the Istituto Nazionale per lo Studio e la
      Cura dei Tumori (Milan, Italy) over 25 years were reviewed. The rates of local
      recurrence, distant metastases, and survival were studied. RESULTS: Two hundred
      fourteen patients presented with primary disease, and 115 patients had locally
      recurrent tumors. The disease-specific survival rate was 75% at 10 years, and the
      local recurrence and distant metastases incidence were 25% and 15%, respectively.
      Presentation with recurrent disease, tumor size (>10 cm), tumor grade (French
      Federation of Cancer Centers grade II or III vs grade I), and positive surgical
      margins were independent predictors of death. Tumor site and radiation therapy
      also played a role, mostly related to their effect on local outcome. Pathologic
      grade and histologic subtype influenced distant metastases. Extrapulmonary
      metastases were associated with poorer postmetastatic disease-specific survival.
      CONCLUSIONS: Myxoid/round cell liposarcomas shared similar prognostic factors
      with other soft tissue sarcomas and had a relatively good clinical outcome. The
      presence of >5% of round cell component singled out a group of patients at
      greater risk of metastases and death but with a broad spectrum of disease
      aggressiveness. Extrapulmonary metastases were a peculiar pattern of myxoid/round
      cell liposarcoma that require special consideration for treatment and prognosis.

PMID- 17510919
TI  - Clinical evaluation of isolated nonvisualized fetal gallbladder.
AB  - OBJECTIVE: Isolated nonvisualized fetal gallbladder (INVFGB) is relatively rare.
      In most cases, the gallbladder will eventually be detected. In some cases
      however, INVFGB may be associated with serious abnormalities, cystic fibrosis
      (CF), aneuploidy, and agenesis of the gall bladder. We describe a clinical
      evaluation of prenatally diagnosed INVFGB. METHODS: Cases of nonvisualized
      gallbladder were first evaluated by serial scans. Cases with no additional
      malformations were designated as INVFGB, and were further evaluated by mutation
      analysis for CF, and amniocentesis for karyotype and microvillar membrane enzymes
      (MME). RESULTS: A total of 22 cases of nonvisualized gallbladder were detected.
      Of these, 2 had additional malformations, and 3 were excluded because of
      incomplete evaluation. Of the remaining 17 cases, 3 (17.6%) had adverse outcomes:
      1 case of CF, 1 case of 47,XXX, and 1 case of multiple congenital anomalies
      detected only postnatally. Abnormal levels of MMEs were detected in 3 cases, 1 of
      which was diagnosed with CF. In 2 cases, the gallbladder was not detected even
      after birth, but development is normal. CONCLUSION: Evaluation of INVFGB should
      include genetic counselling, amniocentesis for karyotype and MME analysis, CFTR
      mutation analysis and repeated ultrasound scans.

PMID- 17510920
TI  - The first prenatal diagnosis for veno-occlusive disease and immunodeficiency
      syndrome, an autosomal recessive condition associated with mutations in SP110.
AB  - OBJECTIVES: We present the first prenatal diagnosis of familial hepatic veno
      occlusive disease with immunodeficiency (VODI). Homozygous mutations in the gene
      SP110 are the genetic basis of VODI. The proband in this report presented at
      three months of age with hepatomegaly hepatic failure and was found to have
      hypogammaglobulinemia. He died one month after hepatic transplant at eight months
      of age due to hemophagocytic syndrome. DNA testing detected a homozygous
      truncating mutation in exon 5; SP110 c.642delC. Prenatal testing was offered to
      this family in a subsequent pregnancy. METHODS: Chorion villus was sampled at 12
      weeks' gestation. DNA was extracted using standard techniques, and sequencing of
      SP110 exon 5 was performed using flanking primers. Maternal contamination was
      excluded by examining STR markers in CVS and maternal DNA. RESULTS: A
      heterozygous SP110 c.642delC mutation was detected in exon 5. This mutation was
      present in heterozygous form in both parents. CONCLUSIONS: The prenatal test
      result is predictive of a child with a normal immune and hepatic phenotype. This
      report presents the first prenatal molecular diagnosis for VODI and shows the
      importance of molecular genetic research in not only defining the aetiology of
      syndromes but also in assisting reproductive choices through the collaboration of
      genetic and feto-maternal services.

PMID- 17510921
TI  - Association of congenital cardiac defects and the C677T methylenetetrahydrofolate
      reductase polymorphism.
AB  - OBJECTIVE: MTHFR C677T polymorphism and hyperhomocysteinemia have been associated
      with congenital malformations of the heart and neural tube defects. A common
      missense mutation in the MTHFR gene (C to T substitution at position 677)
      produces a variant with reduced enzymatic action. The aim of this retrospective
      case control study was to investigate whether the occurrence of the MTHFR
      polymorphism is increased in mothers and fathers of children with a congenital
      heart disease (CHD) in our population. METHODS: We genotyped 31 couples with CHD
      offspring and 31 control couples for this study by obtaining smears from buccal
      gingiva cells and analyzed these for the MTHFR polymorphism by hybridization on
      microarrays. RESULTS: Statistical significance was calculated using the chi
      square test and Pearson-exact test, respectively. The prevalence of homozygosity
      or heterozygosity for the MTHFR polymorphism was not significantly increased in
      parents of CHD affected children. Nevertheless significance was observed for the
      association between aortic arch anomalies and the mothers. CONCLUSIONS: The
      results of this study do not show any significant association between the MTHFR
      C677T polymorphism and CHD in our population. Although the numbers are small (n =
      3), the MTHFR (C677T) polymorphism may be linked to the development of aortic
      arch anomalies.

PMID- 17510922
TI  - Prenatal demonstration of afferent vessels and progressive thrombosis in a
      torcular malformation.
AB  - OBJECTIVES: To elucidate a part of the prenatal natural history of dural sinus
      malformation of the posterior fossa. METHODS: Ultrasound and magnetic resonance
      imaging were performed from 31 to 32 weeks' gestation. RESULTS: We observed the
      progressive development of a thrombus that was visible as an expanding
      hyperechoic round area within a cystic mass of the posterior fossa. It was
      characterized, as expected for a vascular malformation, by the presence of blood
      flow into the aneurismal cavity. Color doppler identified superior sagittal and
      straight sinuses, and distinguished that their flow continued into the dilated
      torcular. Prenatal magnetic resonance imaging confirmed an arteriovenous
      malformation involving the dural sinus. CONCLUSION: The vascular malformation had
      a fixed volume and preceded the thrombosis, which formed within several days. The
      present case is the first report with all the prenatal sonographic features of
      this condition.

PMID- 17510923
TI  - Array-CGH analysis of cell-free fetal DNA in 10 mL of amniotic fluid supernatant.
AB  - BACKGROUND: Previously, we showed that analysis of amniotic fluid (AF)
      supernatant cell-free fetal (cff) DNA using DNA microarrays (array-CGH) allows
      for detection of whole chromosome differences between test and reference DNA.
      Subsequent technical advances have increased both the yield and quality of
      extracted cffDNA. Here we determined whether array-CGH using smaller volumes of
      both fresh and frozen AF cffDNA could identify fetal aneuploidy. METHODS: CffDNA
      was extracted from 10 mL of residual AF supernatant. The test AF samples (n = 10)
      included one with a normal karyotype, and nine with the following fetal
      aneuploidies: trisomies 13 (n = 1), 18 (n = 3), 21 (n = 2), trisomy 9 mosaicism
      (47,XX,+ 9[18]/46,XX[2]), triploidy (69,XXY) and Turner syndrome (45,X). RESULTS:
      Array-CGH using AF cffDNA from aneuploid fetuses, compared to euploid reference
      AF cffDNA, detected whole chromosome aneuploidy in 8 of 9 cases tested, including
      the case of trisomy 9 mosaicism. The case of triploidy was not detected.
      CONCLUSIONS: CffDNA extracted from 10 mL AF supernatant can be analyzed using
      array-CGH to correctly identify human chromosome abnormalities. This technology
      allows for rapid screening of AF samples for whole chromosomal changes by using
      routinely discarded supernatant, and may augment standard prenatal karyotyping
      techniques by providing additional molecular information.

PMID- 17510924
TI  - Clinical implication of isolated right dominant heart in the fetus.
AB  - OBJECTIVE: To evaluate the clinical implication of isolated right dominant heart
      (RDH) in fetal echocardiography. STUDY DESIGN: We reviewed the medical records of
      pregnant women diagnosed with fetal RDH at Asan Medical Center from December 1999
      to December 2005. The criteria of RDH were the ratio of right-to-left atrial and
      ventricular width and the ratio of the diameter of pulmonary artery-to-aorta were
      greater than 1.5. Fetuses with congenital heart disease, including coarctation of
      the aorta (CoA), noncardiac anomalies or chromosomal abnormalities were excluded.
      RESULTS: RDH was identified in 44 fetuses. Twenty-nine (66%) were confirmed to
      have normal heart and 15 (34%) had cardiac anomalies by postnatal
      echocardiogrphy; 11 CoA, 1 interruption of aortic arch, 1 patent ductus
      arteriosus, and 2 ventricular septal defect. Mean gestational age at presentation
      with RDH was later in normal fetuses as compared to fetuses with CoA (p < 0.005).
      Only 26% (4/15) of fetuses presenting with RDH during the second-trimester were
      found to have normal heart postnatally, compared with 86% (25/29) of those
      diagnosed in the third-trimester. CONCLUSION: RDH in the fetus is a risk factor
      for postnatal CoA particularly when diagnosed in the second-trimester, and should
      be an indication for neonatal echocardiography.

PMID- 17510925
TI  - Self-oriented perfectionism in eating disorders.
AB  - OBJECTIVE: To assess perfectionism dimensions in eating disorders in comparison
      with other psychiatric disorders and subjects from the general population.
      METHOD: The Child and Adolescent Perfectionism Scale (CAPS), the Eating Disorders
      Inventory (EDI-2), and the Eating Attitudes Test (EAT) were administered to a
      group of 108 female eating-disordered patients (75 anorexia nervosa and 33
      bulimia nervosa), to a group of 86 female psychiatric patients with anxiety (N =
      32), depressive (N = 38), or adaptive disorders (N = 16), and to 213 healthy
      female participants. RESULTS: Both bulimic and anorexic patients scored higher on
      Self-Oriented Perfectionism (p < 0.001) than the other two groups but not on
      Socially-Prescribed Perfectionism (p = 0.054). Among patients with eating
      disorder, 17.6% obtained a score two standard deviations higher than the mean in
      the healthy comparison group on self-oriented perfectionism; this percentage was
      significantly higher than in the other two groups. The percentage of eating
      disorder patients with high socially-prescribed perfectionism was similar to that
      found in other psychiatric disorders. Moreover, self-oriented perfectionism was a
      predictor of an eating disorder. CONCLUSION: Self-oriented perfectionism is more
      specific to eating disorders than to depressive or anxiety disorders.

PMID- 17510926
TI  - Noncanonical spike-related BOLD responses in focal epilepsy.
AB  - Till now, most studies of the Blood Oxygen Level-Dependent (BOLD) response to
      interictal epileptic discharges (IED) have assumed that its time course matches
      closely to that of brief physiological stimuli, commonly called the canonical
      event-related haemodynamic response function (canonical HRF). Analyses based on
      that assumption have produced significant response patterns that are generally
      concordant with prior electroclinical data. In this work, we used a more flexible
      model of the event-related response, a Fourier basis set, to investigate the
      presence of other responses in relation to individual IED in 30 experiments in
      patients with focal epilepsy. We found significant responses that had a
      noncanonical time course in 37% of cases, compared with 40% for the conventional,
      canonical HRF-based approach. In two cases, the Fourier analysis suggested
      activations where the conventional model did not. The noncanonical activations
      were almost always remote from the presumed generator of epileptiform activity.
      In the majority of cases with noncanonical responses, the noncanonical responses
      in single-voxel clusters were suggestive of artifacts. We did not find evidence
      for IED-related noncanonical HRFs arising from areas of pathology, suggesting
      that the BOLD response to IED is primarily canonical. Noncanonical responses may
      represent a number of phenomena, including artefacts and propagated epileptiform
      activity.

PMID- 17510927
TI  - Outcomes in patients with primary breast cancer and a subsequent diagnosis of
      endometrial cancer : comparison of cohorts treated with and without tamoxifen.
AB  - BACKGROUND: The study compared tumor characteristics and survival in women with
      breast cancer who subsequently developed endometrial cancer with or without a
      history of tamoxifen use. METHODS: The British Columbia Cancer Agency registry
      identified 163 women diagnosed with breast cancer between 1989-1999 who received
      a subsequent diagnosis of endometrial cancer. Of these, 55% (n = 90) had a
      history of tamoxifen use. Outcomes analyzed were breast cancer-specific survival
      (BCSS), endometrial cancer-specific survival (ECSS), and overall survival (OS).
      RESULTS: Median follow-up was 9.4 years. Distributions of age, menopausal status,
      body mass index, and comorbidities were similar in the tamoxifen-treated and
      nontamoxifen cohorts. Proportions of aggressive endometrial cancer subtypes
      including papillary serous, clear cell, and mixed mullerian tumors were higher in
      the tamoxifen cohort (28% vs14%, P = .03). Distributions of endometrial cancer
      grade and stage were similar in the 2 groups (P > .05). Hysterectomy and/or
      oophorectomy were the primary treatments for endometrial cancer in 99% of
      patients, with comparable pelvic control rates in the tamoxifen and nontamoxifen
      groups. At 10 years, patients in the tamoxifen group experienced lower BCSS
      compared with the nontamoxifen group (89% vs 97%, P = .02). No significant
      differences in ECSS and OS were observed between the 2 groups (ECSS 82% and 82%,
      P = .85; and OS 69% v. 66%, P = .85). CONCLUSIONS: In patients with breast cancer
      who developed a subsequent endometrial cancer, tamoxifen-treated patients had
      higher proportions of aggressive endometrial cancer subtypes, but almost all
      cases were amenable to surgery, thus resulting in similar endometrial cancer
      control and survival when compared with nontamoxifen treated patients.

PMID- 17510928
TI  - Identification and quantitation of pyrethroid pesticide residues in vegetables by
      solid-phase extraction and liquid chromatography/electrospray ionization ion trap
      mass spectrometry.
AB  - A quantitative method consisting of solid-phase extraction (SPE) followed by
      liquid chromatography/electrospray ionization ion trap mass spectrometry (LC/ESI
      ITMS) analysis was developed for the identification and quantitation of ten
      pyrethroid pesticides commonly used in vegetables. The best HPLC separation was
      achieved using a gradient program of methanol/water mixture. For the vegetable
      samples, an SPE procedure to clean up the matrices was carried out prior to LC/MS
      analysis. Under the optimum conditions, the limits of quantification of the
      pyrethroid pesticides (tetramethrin, allethrin, fenpropathrin, lambda
      cyhalothrin, cypermethrin, deltamethrin, fenvalerate, bioresmethrin, permethrin
      and bifenthrin) ranged from 0.03 to 0.1 mg kg-1 with relative standard
      deviations<20%, and the mean recoveries ranged from 69.5 to 102.5%. The proposed
      method has been successfully applied to the determination of pyrethroids in six
      vegetables with satisfactory results.

PMID- 17510929
TI  - Determination of amprolium, carbadox, monensin, and tylosin in surface water by
      liquid chromatography/tandem mass spectrometry.
AB  - Antibiotics present in the environment are recently considered as emerging
      contaminants, and have raised increasing concerns about their potential risks to
      ecosystems and human health. In addition to the utilization for treatment,
      antibiotics are also routinely added as supplements in livestock feed to promote
      animal growth. A portion of the administered dose used for these purposes can be
      excreted into animal manure, and land application of the animal manure as plant
      fertilizers enhances the dissemination of antibiotics in the environment. It is a
      common practice to simultaneously administer multiple classes of antibiotics to
      livestock in an animal production farm. This study attempts to develop a protocol
      to determine four commonly used veterinary pharmaceuticals, amprolium, carbadox,
      monensin, and tylosin, in surface runoff from a livestock farm. A single
      cartridge solid-phase extraction procedure was developed to simultaneously
      extract these veterinary antibiotics from surface water which were subsequently
      analyzed by liquid chromatography/tandem mass spectrometry. The extraction
      recoveries of spiked samples ranged from 89 to 113%, and the limits of
      quantitation were 8, 25, 1, and 35 ng/L for amprolium, carbodox, monensin, and
      tylosin, respectively. In the surface runoff from a livestock farm, amprolium was
      most frequently detected with the concentration range of 10-288 ng/L. Monensin
      was frequently detected with concentrations up to 37 ng/L. Tylosin was detected
      in two out of eleven samples, and carbadox was not detected in the surface
      runoff. The results indicate that the developed analytical method can be utilized
      to determine multiple classes of veterinary antibiotics present in surface runoff
      originating from animal farms.

PMID- 17510930
TI  - Determination of epoxidized soybean oil by gas chromatography/single quadrupole
      and tandem mass spectrometry stable isotope dilution assay.
AB  - PVC lids of glass jars often contain epoxidized soybean oil (ESBO), able to
      migrate and contaminate food. To establish a stable isotope dilution assay
      (SIDA), the 13C18-labelled internal standard ethyl 9,10,12,13
      diepoxyoctadecanoate (13C(18:2E)Et) was synthesized, providing after sample
      preparation the same retention time as methyl 9,10,12,13-diepoxyoctadecanoate
      ((18:2E)Me), commonly used as a marker for ESBO in gas chromatographic (GC)
      analysis. For eleven different food matrices, the GC capillary columns VF-17ms,
      DB1701 and DB1 were tested with single quadrupole (GC/MS) as well as tandem mass
      spectrometric detection (GC/MS/MS). Overall, the VF-17ms column coupled with
      MS/MS detection showed the best results in terms of separation and sensitivity.
      The method validation for the matrix spiked olive oil resulted in a limit of
      detection (LOD) of 5 mg kg-1, a limit of quantification (LOQ) of 11 mg kg-1, a
      mean recovery (n=5, c=106.5 mg kg-1) of 99.7+/-5.5%, with a repeatability (within
      run precision) of 6.0%. By means of GC/MS an LOQ of 21 mg kg-1 and a mean
      recovery (n=5, c=106.5 mg kg-1) of 103.3+/-0.8% with a repeatability of 0.9% were
      determined.

PMID- 17510932
TI  - Metabolic fingerprinting using direct flow injection electrospray ionization
      tandem mass spectrometry for the characterization of proanthocyanidins from the
      barks of Hancornia speciosa.
AB  - Direct flow injection electrospray ionization ion trap tandem mass spectrometry
      (ESI-IT-MS/MS) was used to investigate the polyphenolic compounds present in an
      infusion from the barks of Hancornia speciosa Gom. (Apocynaceae), a native
      Brazilian plant popularly known as 'mangabeira', used as a source of nutrition
      and against gastric disorders. After a simple sample filtration pretreatment the
      characteristic fingerprint of the infusion was performed in negative ion ESI mode
      in a few minutes. At low capillary-voltage activation, the deprotonated molecules
      ([M--H]-) were observed and using collision-induced dissociation the product ion
      spectra showed the presence of a homologous series of B-type proanthocyanidins,
      as well as another series containing their respective C-glycosylated derivatives,
      with a degree of polymerization from 1 up to 6 units of interlinked catechins.
      Therefore, direct flow injection allowed us to identify the key compounds without
      preparative isolation of the components.

PMID- 17510933
TI  - Longitudinal differences in 15N between mothers and offspring during and after
      weaning in a small cooperative mammal, the meerkat (Suricata suricatta).
AB  - Gestation and subsequent lactation are energetically costly life history events
      for mammalian females. We used longitudinal delta15N data from hair samples from
      offspring and their mothers to explore lactation patterns in a small cooperative
      mammal, the meerkat (Suricata suricatta). Lactation enriched hair from meerkat
      offspring in 15N compared with that of their mothers, and this enrichment
      gradually declined after weaning. Although the observed peak enrichment of
      approximately 1 per thousand was substantially below the predicted levels of
      trophic enrichment in capital versus income breeders, we suggest that our results
      reflect an income breeding tactic in this species. Our study supports the notion
      that delta15N analyses can be a useful tool to investigate lactation schedules in
      mammals. However, reliable conclusions from 15N data regarding the nutritional
      tactics of mammalian females during reproduction may be limited by our scant
      understanding of the effects of various physiological variables on isotope
      assimilation.

PMID- 17510934
TI  - Factors influencing enantiomeric fractions of hexabromocyclododecane measured
      using liquid chromatography/tandem mass spectrometry.
AB  - Hexabromocyclododecane (HBCD), the most heavily produced of the cycloaliphatic
      brominated flame retardants (BFRs), is a mixture of three predominant
      diastereomers (alpha-, beta-, and gamma-HBCD), each with a corresponding pair of
      enantiomers. We have investigated the liquid chromatography/mass spectrometry
      (LC/MS) behaviour of the HBCD enantiomers, and demonstrated that enantiomeric
      fractions (EFs) calculated using data uncorrected for instrument and/or matrix
      effects can result in potentially inaccurate EF values. However, use of labelled
      surrogates effectively corrects for these effects. Experiments with racemic HBCD
      standards indicate that chromatographic factors, including mobile phase
      composition and column bleed from chiral stationary phases, may be contributors
      to variations in the mass spectrometric response of the HBCD enantiomers.

PMID- 17510935
TI  - A simple and selective method for the measurement of leucine and isoleucine from
      plasma using electrospray ionization tandem mass spectrometry.
AB  - An analytical method was developed for the rapid and accurate quantification of
      leucine (LEU) and isoleucine (ILE) from plasma using electrospray ionization
      tandem mass spectrometry (ESI-MS/MS). The two isomeric amino acids were
      selectively detected using fragment ions unique to each compound. As a result,
      the need for chromatographic separation was avoided allowing for faster analysis
      (3 min). The possibility of any considerable interference between the two
      transitions was closely monitored, with no significant interference being
      observed. The presence of interfering compounds in plasma was also evaluated and
      found to minimal. The method was evaluated based upon linearity, with r2>or=0.995
      for both compounds, and accuracy, with no more than 8% deviation from the
      theoretical value.

PMID- 17510936
TI  - Determination of twenty-five elements in lichens by sector field inductively
      coupled plasma mass spectrometry and microwave-assisted acid digestion.
AB  - A simple and efficient digestion method for rapid sample preparation and
      quantification of 25 chemical elements in lichens by sector field inductively
      coupled plasma mass spectrometry is described. A microwave (MW)-assisted acid
      digestion was carried out at atmospheric pressure simultaneously handling up to
      80 samples in screw-capped disposable polystyrene tubes. This digestion procedure
      was compared with the established MW digestion in closed vessels in order to
      examine its potential applicability in routine analysis for environmental
      monitoring. Three certified reference materials, i.e. BCR 482 (lichens), BCR 62
      (olive leaves) and BCR 100 (beech leaves), as well as a small set of real samples
      were analyzed. Limits of quantification, accuracy and precision of the method
      were assessed. The majority of the elements were totally recovered from the
      lichens and from the other vegetable matrices. Low contamination risk,
      simplicity, time-saving, and applicability in routine analyses make this method
      very suitable for use in extensive screening campaigns.

PMID- 17510937
TI  - Fast profiling of the integral metabolism of flavonols in the active fraction of
      Gossypium herbaceam L. using liquid chromatography/multi-stage tandem mass
      spectrometry.
AB  - A method of fast profiling the constituents in an active herbal extract and their
      metabolites in biological fluids based on the combination of fragmentation
      behavior and metabolic pathways is described. The complementary information from
      fragmentation behavior and metabolic pathways helped not only to identify the
      structure of parent constituents and metabolites, but also to correlate
      metabolites back to their parent forms. An active fraction obtained from
      Gossypium herbaceam L., named AB-8-2, and bile samples from rats administered it
      orally and intravenously were analyzed using high-performance liquid
      chromatography/multi-stage tandem mass spectrometry (HPLC-MSn) in a single
      chromatographic run. Fifty-eight flavonols comprising mixed sulfate, methyl,
      glucuronide and glycoside derivatives of quercetin or kaempferol were detected,
      including several groups of isomers. By contrasting the analytical results from
      AB-8-2 and from bile samples derived from different administration routes, a
      profile of the biotransformation of the flavonols in AB-8-2 was obtained. The
      results should be of benefit in targeting potential active ingredients in complex
      mixtures, such as herbs or their active extracts.

PMID- 17510939
TI  - Rapid structural characterization of isomeric benzo[c]phenanthridine alkaloids
      from the roots of Zanthoxylum nitidium by liquid chromatography combined with
      electrospray ionization tandem mass spectrometry.
AB  - The fragmentation mechanism of six alkaloids, namely: dihydronitidine,
      dihydrochelerythrine, 8-acetonyldihydronitidine, 8-acetonyldrochelerythrine,
      nitidine and 1,3-bis(8-dihydronitidinyl)acetone, was investigated by electrospray
      ionization multi-stage tandem mass spectrometry (ESI-MSn). Tandem mass
      spectrometry experiments indicated that different substitution sites of the
      methoxyl groups at C-9 and C-10 or at C-10 and C-11 determined the different
      abundances of the MS2 fragmentation ions using the same collision energy.
      According to the different abundances of MS2 product ions, positional isomeric
      benzo[c]phenanthridine alkaloids can be differentiated. Moreover, ten
      constituents in the crude alkaloidol extract from the roots of Zanthoxylum
      nitidium were rapidly identified by high-performance liquid chromatography
      coupled with tandem mass spectrometry (HPLC/MSn), through comparing the retention
      times and ESI-MSn spectra with the authentic standards. This work demonstrates
      that not only the characteristic fragments but also the characteristic abundances
      of the fragment ions can be used for detailed structural characterization.

PMID- 17510940
TI  - Carbon-isotopic composition of soil-respired carbon dioxide in static closed
      chambers at equilibrium.
AB  - The carbon-isotopic composition (delta13C) of soil-respired CO2 has been employed
      to evaluate soil carbon-cycling processes and the contribution of soil CO2
      emissions to canopy and tropospheric air. These evaluations can be successful
      only when accurate isotope values of soil-respired CO2 are available. Here, we
      tested the robustness of delta13C values of soil-respired CO2 obtained after long
      incubations in static closed chambers that were initially flushed with soil air.
      The rationale of this approach is that the equilibrium carbon-isotope values of
      chamber-headspace CO2 are theoretically equal to those of CO2 produced within the
      soil. Static closed chambers were installed in replicated grass monocultures, and
      measurements of headspace CO2 concentrations and delta13C values were performed
      at regular time intervals for 24 h in July 2005. The results revealed no
      significant effects of grass species on headspace CO2 concentrations or delta13C
      values (repeated measures analysis of variance (ANOVA), P>0.1). As predicted by
      theory, isotope values asymptotically approached equilibrium conditions, which in
      our experimental setting occurred after 10 h. This good match between model
      predictions and our results suggests that an accurate determination of delta13C
      values of CO2 produced within soils is obtained through the isotopic measurement
      of chamber-headspace CO2 once equilibrium conditions have been reached with the
      underlying soils. An additional advantage of this approach is that only one
      sample per chamber is required, which, combined with the low uncertainties of
      these measurements, facilitates the investigation of the spatial (landscape)
      variability of soil-respired CO2.

PMID- 17510941
TI  - Rapid separation and identification of phenolic and diterpenoid constituents from
      Radix Salvia miltiorrhizae by high-performance liquid chromatography diode-array
      detection, electrospray ionization time-of-flight mass spectrometry and
      electrospray ionization quadrupole ion trap mass spectrometry.
AB  - High-performance liquid chromatography-diode array detection (HPLC-DAD),
      electrospray ionization time-of-flight mass spectrometry (HPLC-ESI-TOF-MS) and
      electrospray ionization quadrupole ion trap mass spectrometry (HPLC-ESI-MSn) were
      used for the isolation, identification and structural analysis of water-soluble
      phenolic and nonpolar diterpenoid constituents in Dan-shen (Radix Salvia
      miltiorrhizae) which was prepared by sonication in 70% methanol. Mass spectra
      were obtained by ESI-TOF-MS and electrospray ionization quadrupole ion trap mass
      spectrometry (ESI-QIT-MS). A formula database of known constituents in Dan-shen
      was established and most constituents were rapidly identified by HPLC-DAD/ESI-TOF
      MS by matching their accurate molecular masses with the formulae of the compounds
      in the database. Compounds with the same molecular formula could not be
      differentiated by TOF-MS; however, QIT-MS could differentiate those compounds and
      elucidate their structures based on their characteristic fragmentation. HPLC-DAD,
      HPLC/ESI-TOF-MS and HPLC/ESI-MSn provided complementary information for the
      identification of the constituents in Dan-shen. Forty constituents were
      identified in 30 min based on their positive and negative ion ESI mass spectra
      and liquid chromatographic information. Thus the method described is useful for
      the rapid analysis of multiple constituents in Dan-shen.

PMID- 17510942
TI  - Rapid screening assay of trimethylaminuria in urine with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Trimethyamine (TMA) and trimethylamine N-oxide (TMAO) are the most important
      urine parameters for diagnosing and monitoring trimethylaminuria. A rapid,
      simple, and specific method based on matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOFMS) was developed to determine the
      presence of TMA and TMAO in urine samples from patients with trimethylaminuria.
      Formation of the quaternary tetramethylamino iodide by derivatization of TMA with
      methyl iodide allows measurement of TMA by MALDI-TOFMS. The method is repeatable
      and reproducible, with coefficients of variance (CVs)<3%. This new method was
      used for direct determination of TMA and TMAO in urine specimens obtained from
      normal children and patients. The proposed method allows for rapid and reliable
      measurements of TMA and TMAO in urine specimens from patients affected by
      trimethylaminuria.

PMID- 17510943
TI  - The association study between DHCR24 polymorphisms and Alzheimer's disease.
AB  - DHCR24 gene in chromosome 1 encodes seladin 1, a cholesterol synthesizing enzyme.
      Seladin 1 protects neurons from Abeta(42) mediated toxicity and participates in
      regulation of Abeta(42) formation by organizing the placement of APP cleaving
      beta-secretase in cholesterol-rich detergent-resistant membrane domains (DRMs).
      In Alzheimer's disease (AD) the level of seladin 1 in affected neurons is
      reduced, DRMs are disorganized and Abeta(42) formation is increased. To examine
      genetic association of the DHCR24 with AD, we genotyped four single nucleotide
      polymorphism (SNP) sites (rs638944, rs600491, rs718265, and rs7374) in 414
      Finnish AD cases and 459 controls and calculated the allelic and genotypic
      distribution of both cases and controls. The single locus association analysis
      indicated that men carrying the T allele of rs600491 had an increased risk of AD
      (OR 1.7 95% CI 1.2-2.4; P = 0.004, Bonferroni corrected P = 0.048 with 12 tests).
      We estimated haplotypes of SNPs rs638944 and rs600491 between cases and controls
      and found overall distribution of haplotypes highly significant (P < 0.001).
      There was a common protective haplotype TC with frequency of 0.22 in cases and
      0.30 in controls (P < 0.001) and a risk haplotype GC with frequency of 0.10 in
      cases and 0.05 in controls (P < 0.001). We also measured CSF Abeta(42), tau and
      phosphorylated tau (ptau) levels in a subgroup of AD cases (n = 44) and controls
      (n = 10) and found that AD cases that carry rs718265 GG had lower levels of
      Abeta(42) than other genotype carriers. Our findings indicate that DHCR24 gene
      may be associated with AD risk.

PMID- 17510944
TI  - Molecular genetic studies of DMT1 on 12q in French-Canadian restless legs
      syndrome patients and families.
AB  - Converging evidence from clinical observations, brain imaging and pathological
      findings strongly indicate impaired brain iron regulation in restless legs
      syndrome (RLS). Animal models with mutation in (DMT1) divalent metal transporter
      1 gene, an important brain iron transporter, demonstrate a similar iron
      deficiency profile as found in RLS brain. The human DMT1 gene, mapped to
      chromosome 12q near the RLS1 locus, qualifies as an excellent functional and
      possible positional candidate for RLS. DMT1 protein levels were assessed in
      lymphoblastoid cell lines from RLS patients and controls. Linkage analyses were
      carried out with markers flanking and within the DMT1 gene. Selected patient
      samples from RLS families with compatible linkage to the RLS1 locus on 12q were
      fully sequenced in both the coding regions and the long stretches of UTR
      sequences. Finally, selected sequence variants were further studied in
      case/control and family-based association tests. A clinical association of anemia
      and RLS was further confirmed in this study. There was no detectable difference
      in DMT1 protein levels between RLS patient lymphoblastoid cell lines and normal
      controls. Non-parametric linkage analyses failed to identify any significant
      linkage signals within the DMT1 gene region. Sequencing of selected patients did
      not detect any sequence variant(s) compatible with DMT1 harboring RLS causative
      mutation(s). Further studies did not find any association between ten SNPs,
      spanning the whole DMT1 gene region, and RLS affection status. Finally, two DMT1
      intronic SNPs showed positive association with RLS in patients with a history of
      anemia, when compared to RLS patients without anemia.

PMID- 17510945
TI  - Catechol-O-methyltransferase polymorphism (COMT) in suicide attempters: a
      possible gender effect on anger traits.
AB  - Anger-related personality traits are considered contributory risk factors for
      suicidal behavior. According to twin studies, they are partially under genetic
      control and their various clinical expressions have been associated with
      serotonergic and catecholaminergic activities. A functional polymorphism on the
      human catechol-O-methyltransferase (COMT) gene, which codes for the
      catecholamines inactivating enzyme COMT, has been shown to influence aggressive
      and anger-related traits in various clinical populations. The aim of the present
      study was to investigate the association between anger traits (as characterized
      by the State-Trait Anger Expression Inventory, STAXI) and COMT Val158Met
      polymorphism in suicide attempters (n = 427) and control subjects (n = 185).
      Results showed that the high activity genotype (Val/Val) was more frequent in
      suicide attempters than in normal controls. Moreover, the Val/Val genotype
      markedly affected the scores on two STAXI subscales--Trait Anger and Anger
      Control--in female suicide attempters, thus suggesting a possible gender effect
      of the COMT genotype on a stable personality trait. These results are discussed
      in the light of recently published data on the effect of COMT Val158Met
      polymorphism on different cognitive and behavioral traits.

PMID- 17510946
TI  - Association of genetic variants of ABCA1 with Alzheimer's disease risk.
AB  - ABCA1 plays key roles in cholesterol transport and apolipoprotein E (APOE)
      metabolism in the brain. To evaluate the relationship between ABCA1 genetic
      variants and Alzheimer's disease (AD), independently or in concert with the APOE
      epsilon4 allele, we examined three ABCA1 polymorphisms located in the coding
      region (R219K, I883M, and R1587K) and two ABCA1 polymorphisms in the promoter
      region (C-14T and C-477T) in a group of 372 Spanish AD patients and 440 controls.
      The ABCA1 219K, 883I, 1587R haplotype was significantly associated with AD,
      conferring a risk of 1.78 (P = 0.007). The ABCA1 C-14T polymorphism modified the
      risk of AD in an APOE epsilon4 allele-dependent fashion: in APOE epsilon4
      carriers, homozygous for the ABCA1 -14T allele had 3.7 times higher risk of
      developing AD (OR = 13.99) than carriers of the ABCA1 -14CC and CT genotypes (OR
      = 3.79). These data suggest that the development of AD might be influenced by
      either a qualitative change of the ABCA1 protein caused by coding region variants
      (219K, 883I, and 1587R), or by a quantitative change in ABCA1 expression caused
      by promoter region variant (-14T) in concert with the APOE epsilon4 allele.

PMID- 17510947
TI  - A review of association and linkage studies for genetical analyses of learning
      disorders.
AB  - Learning disorders (LD) commonly comprise of a heterogeneous group of disorders
      manifested by unexpected problems in some children's experiences in the academic
      performance arena. These problems especially comprise of a variety of disorders
      which may be subclassified to attention-deficit hyperactivity disorder (ADHD),
      reading disability (RD), specific language impairment (SLI), speech-sound
      disorder (SSD), and dyspraxia. The aim of this review is to summarize the current
      molecular studies and some of the most exciting recent developments in molecular
      genetic research on LD. The findings for the association and linkage of LD with
      candidate genes will help to set the research agendas for future studies to
      follow.

PMID- 17510948
TI  - The Val66Met polymorphism of the brain-derived neurotrophic factor gene is
      associated with psychotic feature and suicidal behavior in Japanese major
      depressive patients.
AB  - Recent researches have suggested that brain-derived neurotrophic factor (BDNF)
      may be implicated in the pathophysiology of mood disorder. This study examined
      the association between the BDNF Val66Met polymorphism and major depressive
      disorder (MDD) in a Japanese population. We genotyped the BDNF Val66Met
      polymorphism in 154 major depressive patients and 154 age- and sex-matched
      control subjects. The genotypic distributions and allele frequencies were similar
      among the patients and control subjects. When the relationships of the
      polymorphism with several clinical variables (i.e., age, sex, age of onset,
      number of episode, presence of psychotic features, suicidal behavior, and family
      history) were examined, the dose of Met allele had significant effects on
      psychotic feature and suicidal behavior and family history. These results suggest
      that the BDNF Val66Met polymorphism is not related to the development of MDD but
      related to clinical features of MDD in a Japanese population.

PMID- 17510949
TI  - A novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's
      disease in Chinese.
AB  - Recent genetic studies have shown that variants of the ATP-binding cassette
      transporter A1, ABCA1, may be implicated in the pathogenesis of Alzheimer's
      disease (AD). In this case-control study, a panel of 19 single nucleotide
      polymorphisms (SNP) (including three amino-acid-coding SNPs used for replication
      of previous work, and 16 newly selected intronic tag SNPs) was genotyped.
      Nominally significant single marker P-values were observed in four SNPs, with the
      highest score of 0.003 for rs2297404 (OR = 1.88, 95%CI 1.23-2.87). In addition,
      six distinct linkage disequilibrium (LD) blocks were detected. LD block1 harbored
      three nominally significant SNPs (rs2297404, rs2230808, and rs2020927), and
      showed a different haplotype structure in the affected and unaffected groups. Of
      the four haplotypes identified, haplotype2 (CAC) was more prevalent in the
      disease group (0.323 in AD vs. 0.202 in control); while haplotype1 (TGG) was over
      represented in the healthy controls (0.595 in control vs. 0.493 in AD),
      indicating disease risk conferring possibility of haplotype2. After doubling the
      sample size, the three nominally significant SNPs were still significantly
      associated with AD. Although coding SNP (rs2230808) was confirmed to have a
      significant association with AD, prediction of the effects of an amino acid
      substitution SNP rs2230808 (R1587K) on the three-dimensional structure and
      function of the ABCA1 protein using PolyPhen program revealed that it is unlikely
      to be functionally significant. However, the adjacent rs2297404 in the same LD
      block is potentially functionally significant because of its position in the
      immediate vicinity of a splicing branch site. Further functional analysis of this
      polymorphism should be a high priority.

PMID- 17510950
TI  - The effect of genetic variation of the serotonin 1B receptor gene on impulsive
      aggressive behavior and suicide.
AB  - Impulsive-aggressive behaviors (IABs) are regarded as possible suicide
      intermediate phenotypes, mediating the relationship between genes and suicide
      outcome. In this study, we aimed to investigate the putative relationship between
      genetic variation at the 5-HT1B receptor gene, which in animal models is involved
      in impulse-aggression control, IABs, and suicide risk. We investigated the
      relationship of variation at five 5-HT1B loci and IAB measures in a sample of 696
      subjects, including 338 individuals who died by suicide and 358 normal
      epidemiological controls. We found that variation at the 5-HT1B promoter A-161T
      locus had a significant effect on levels of IABs, as measured by the Buss-Durkee
      Hostility Inventory (BDHI). Suicides also differed from controls in distribution
      of variants at this locus. The A-161T locus, which seems to impact 5-HT1B
      transcription, could play a role in suicide predisposition by means of mediating
      impulsive-aggressive behaviors.

PMID- 17510951
TI  - Effect of interleukin-1beta gene functional polymorphism on dorsolateral
      prefrontal cortex activity in schizophrenic patients.
AB  - Hypoactivity of the dorsolateral prefrontal cortex (DLPFC) during cognitive tasks
      is among the most consistent findings in schizophrenia. The biological factors
      contributing to this hypofrontality are only partially known. Previous reports
      have shown the influence of genes mapped to IL-1 cluster (i) in the risk to
      develop schizophrenia and (ii) on brain morphological abnormalities in these
      patients. Moreover, Interleukin-1beta (IL-1beta), encoded by IL-1B gene (IL-1
      cluster, chromosome 2q13) has a key role in dopaminergic differentiation and
      dendrite growth in developing cortical neurons. The authors explored the role of
      a genetic functional polymorphism at IL-1B gene in relation to DLPFC activity.
      DLPFC (left and right) metabolic activity was measured in a sample of 19 DSM-IV
      diagnosed schizophrenic patients of Spanish origin using a procedure based on
      MRI/PET image fusion. During PET studies, subjects performed a contingent
      Continuous Performance Test aiming to activate DLPFC. Functional promoter
      polymorphism -511 C/T (rs16944) of IL-1B gene was genotyped in these patients.
      Those patients who were allele 2 (-511 T) carriers showed a lower metabolic
      activity in the left DLPFC with respect to patients homozygous for allele 1 (-511
      C) (U = 16, z = -2.32, P = 0.02). Our results suggest that hypofrontality
      reported in some schizophrenic patients might be explained, at least in part, by
      this functional polymorphism at IL-1B gene. Genetic variants with influence on
      brain functionality may account for the neurocognitive heterogeneity observed in
      schizophrenic patients.

PMID- 17510952
TI  - Investigating the role of p11 (S100A10) sequence variation in susceptibility to
      major depression.
AB  - Recent evidence suggests a potential role for the p11 gene in conferring risk to
      depressive disorders. p11 has been shown to influence serotonergic transmission,
      and its expression was found to be reduced in a mouse model of depression, as
      well as in post-mortem brain tissue from major depressive disorder (MDD) cases.
      In the present study, we tested for rare variants in p11 by resequencing
      promoter, exonic and flanking intronic regions in 176 MDD cases and 176 matched
      controls. We also assessed common variation by genotyping eight single nucleotide
      polymorphisms (SNPs), seven tag SNPs and one found through resequencing, in 641
      cases and 650 controls. Resequencing revealed nine novel rare variants, including
      a missense mutation (Asp60Glu) observed in one case and one control, and four
      variants that occurred only in cases and not controls. The number of rare
      variants in cases did not exceed that expected by chance for the length of
      sequence analyzed, and also was not significantly greater than that observed in
      controls. Resequencing also identified two known SNPs, one (rs4845720) of which
      was significantly more frequent in cases than controls in the resequenced sample
      (3.1% vs. 0.9%, P = 0.03), though not in the larger sample (3% vs. 2%, P = 0.15).
      None of the tag SNPs showed any evidence of association. Our results do not
      support a major role for either common or rare p11 SNPs with MDD. Several
      limitations of the study are discussed.

PMID- 17510953
TI  - The influence of urban/rural residency on depressive symptoms is moderated by the
      serotonin receptor 2A gene.
AB  - Gene-environment interactions are thought to be involved in the development of
      depression. Here we examined the interaction effect between urban/rural residency
      and the serotonin receptor 2A (HTR2A) gene on subclinical depressive symptoms.
      The participants were 1,224 Finnish men and women being followed in the on-going
      population-based study of "Cardiovascular Risk in Young Finns". Urban/rural
      residency was determined on the basis of a (1) subjective report and (2) the
      population density of the residential area. Depressive symptoms were measured in
      two test settings four years apart. There was a significant gene-environment
      interaction, such that the urban residency was associated with low depressive
      symptoms in individuals carrying the T/T or T/C genotype of the T102C
      polymorphism, but not in those carrying the C/C genotype. The T allele was
      associated with high depressive symptoms in remote rural areas, but with low
      depressive symptoms in urban or suburban areas. The gene-environment interaction
      was not accounted by level of education, social support, unemployment, or
      partnership status. The HTR2A gene may be involved in the development of
      depression by influencing how individuals respond to environmental conditions.

PMID- 17510954
TI  - Generation of blood group specificity: new insights from structural studies on
      the complexes of A- and B-reactive saccharides with basic winged bean agglutinin.
AB  - Basic winged bean agglutinin binds A-blood group substance with higher affinity
      and B-blood group substance with lesser affinity. It does not bind the O
      substance. The crystal structures of the lectin, complexed with A-reactive and B
      reactive di and tri saccharides, have been determined. In addition, the complexes
      of the lectin with fucosylated A-trisaccharides and B-trisaccharides and with a
      variant of the A-trisaccharide have been modeled. These structures and models
      provide valuable insights into the structural basis of blood group specificities.
      All the four carbohydrate binding loops of the lectin contribute to the primary
      combining site while the loop of variable length contributes to the secondary
      binding site. In a significant advance to the current understanding, the
      interactions at the secondary binding site also contribute substantially, albeit
      in a subtle manner, to determine the blood group specificity. Compared with the
      interactions of the B-trisaccharide with the lectin, the third sugar residue of
      the A-reactive trisacharide forms an additional hydrogen bond with a lysine
      residue in the variable loop. In the former, the formation of such a hydrogen
      bond is prevented by a shift in the orientation of third sugar resulting from an
      internal hydrogen bond in it. The formation of this bond is also facilitated by
      an interaction dependent change in the rotamer conformation of the lysyl residue
      of the variable loop. Thus, the difference in the interactions at the secondary
      site is generated by coordinated movements in the ligand as well as the protein.
      A comparison of the crystal structure and the model of the complex involving the
      variant of the A-trisaccharide results in the delineation of the relative
      contributions of the interactions at the primary and the secondary sites in
      determining blood group specificity.

PMID- 17510955
TI  - Conformational contagion in a protein: structural properties of a chameleon
      sequence.
AB  - Certain sequences, known as chameleon sequences, take both alpha- and beta
      conformations in natural proteins. We demonstrate that a wild chameleon sequence
      fused to the C-terminal alpha-helix or beta-sheet in foreign stable proteins from
      hyperthermophiles forms the same conformation as the host secondary structure.
      However, no secondary structural formation is observed when the sequence is
      attached to the outside of the secondary structure. These results indicate that
      this sequence inherently possesses an ability to make either alpha- or beta
      conformation, depending on the sequentially neighboring secondary structure if
      little other nonlocal interaction occurs. Thus, chameleon sequences take on a
      satellite state through contagion by the power of a secondary structure. We
      propose this "conformational contagion" as a new nonlocal determinant factor in
      protein structure and misfolding related to protein conformational diseases.

PMID- 17510956
TI  - Atomic contacts in protein structures. A detailed analysis of atomic radii,
      packing, and overlaps.
AB  - A rigorous quantitative assessment of atomic contacts and packing in native
      protein structures is presented. The analysis is based on optimized atomic radii
      derived from a set of high-resolution protein structures and reveals that the
      distribution of atomic contacts and overlaps is a structural constraint in
      proteins, irrespective of structural or functional classification and size.
      Furthermore, a newly developed method for calculating packing properties is
      introduced and applied to sets of protein structures at different levels of
      resolution. The results show that limited resolution yields decreasing packing
      quality, which underscores the relevance of packing considerations for structure
      prediction, design, dynamics, and docking.

PMID- 17510957
TI  - Beta-strand recombination in tricalbin evolution and the origin of synaptotagmin
      like C2 domains.
AB  - Two protein families involved in membrane traffic, tricalbins and synaptotagmins,
      contain several copies of C2 domains and are related based on their sequence and
      domain architecture. Paradoxically, tricalbin and synaptotagmin C2 domains belong
      to different structural types with apparent circular permutation of terminal beta
      strands. To understand whether a topological switch took place, we analyzed
      tricalbin and synaptotagmin-like C2 domains using two-dimensional structural
      analysis. We found that yeast tricalbins contain five to six C2 domains. One of
      these C2 domains possesses many features of synaptotagmin-like C2 domains and
      also carries a conserved C-terminal strand that is similar to its structural
      equivalent in synaptotagmin-like C2 domains, suggesting a structural permutation
      event. Indeed, among higher eukaryotes, animal tricalbins have evolved a C2
      domain with synaptotagmin-like topology indicating that the structural conversion
      has taken place. Investigation of plant synaptotagmins, however, proves that they
      are direct tricalbin orthologs. Our analysis shows that beta-strand recombination
      is a possible evolutionary mechanism to generate new structural topologies with
      altered functional properties.

PMID- 17510958
TI  - Structure-based virtual ligand screening with LigandFit: pose prediction and
      enrichment of compound collections.
AB  - Virtual ligand screening methods based on the structure of the receptor are
      extensively used to facilitate the discovery of lead compounds. In the present
      study, we investigated the LigandFit package on four different proteins
      (coagulation factor VIIa, estrogen receptor, thymidine kinase, and
      neuraminidase), a relatively large compound collection of 65,560 unique "drug
      like" molecules and four focused libraries (1950 molecules each). We performed
      virtual screening experiments with the large database and evaluated six scoring
      functions available in the package (DockScore, LigScore1, LigScore2, PLP1, PLP2,
      and PMF). The results showed that LigandFit is an efficient program, especially
      when used with LigScore1. Similar computations were carried out using focused
      libraries. In this situation the LigScore1 scoring function outperformed the
      other ones on three out of the four proteins tested. Even for the difficult
      neuraminidase case, the LigandFit/LigScore1 combination was still reasonably
      successful. Assessment of docking accuracy was also performed and again, we found
      that LigandFit (with DockScore and the CFF parameters) was performing well. On
      the basis of these results and observed increased enrichments after
      LigandFit/Ligscore1 screening on focused libraries, we suggest that using this
      program as a final step of a hierarchical protocol can be very beneficial to
      assist lead finding.

PMID- 17510959
TI  - A model-based proposal for the role of UreF as a GTPase-activating protein in the
      urease active site biosynthesis.
AB  - UreF is a protein that plays a role in the in vivo urease activation as a
      chaperone involved in the insertion of two Ni(2+) ions in the apo-urease active
      site. The molecular details of this process are unknown. In the absence of any
      molecular information on the UreF protein class, and as a step toward the
      comprehension of the relationships between UreF function and structure, we
      applied a structural modeling approach to infer useful biochemical knowledge on
      Bacillus pasteurii UreF (BpUreF). Similarity searches and multiple alignment of
      UreF protein sequences indicated that this class of proteins has a low homology
      with proteins of known structure. Fold recognition methods were therefore used to
      identify useful protein structural templates to model the structure of BpUreF. In
      particular, the templates belong to the class of GTPase-activating proteins.
      Modeling of BpUreF based on these templates was performed using the program
      MODELLER. The structure validation yielded good statistics, indicating that the
      model is plausible. This result suggests a role for UreF in urease active site
      biosynthesis as a regulator of the activity of UreG, a small G protein involved
      in the in vivo apo-urease activation process and established to catalyze GTP
      hydrolysis.

PMID- 17510960
TI  - Studies of the molten globule state of ferredoxin: structural characterization
      and implications on protein folding and iron-sulfur center assembly.
AB  - The biological insertion of iron-sulfur clusters (Fe-S) involves the interaction
      of (metallo) chaperons with a partly folded target polypeptide. In this respect,
      the study of nonnative protein conformations in iron-sulfur proteins is relevant
      for the understanding of the folding process and cofactor assembly. We have
      investigated the formation of a molten globule state in the [3Fe4S][4Fe4S]
      ferredoxin from the thermophilic archaeon Acidianus ambivalens (AaFd), which also
      contains a structural zinc site. Biophysical studies have shown that, at acidic
      pH, AaFd retains structural folding and metal centers. However, upon increasing
      the temperature, a series of successive modifications occur within the protein
      structure: Fe-S disassembly, loss of tertiary contacts and dissociation of the
      Zn(2+) site, which is simultaneous to alterations on the secondary structure.
      Upon cooling, an apo-ferredoxin state is obtained, with characteristics of a
      molten globule: compactness identical to the native form; similar secondary
      structure evidenced by far-UV CD; no near-UV CD detected tertiary contacts; and
      an exposure of the hydrophobic surface evidenced by 1-anilino naphthalene-8
      sulfonic acid (ANS) binding. In contrast to the native form, this apo ferredoxin
      state undergoes reversible thermal and chemical unfolding. Its conformational
      stability was investigated by guanidinium chloride denaturation and this state is
      approximately 1.5 kcal mol(-1) destabilised in respect to the holo ferredoxin.
      The single tryptophan located nearby the Fe-S pocket probed the conformational
      dynamics of the molten globule state: fluorescence quenching, red edge emission
      shift analysis and resonance energy transfer to bound ANS evidenced a restricted
      mobility and confinement within a hydrophobic environment. The possible
      physiological relevance of molten globule states in Fe-S proteins and the
      hypothesis that their structural flexibility may be important to the
      understanding of metal center insertion are discussed.

PMID- 17510961
TI  - Parallel tempering molecular dynamics folding simulation of a signal peptide in
      explicit water.
AB  - Parallel temperature molecular dynamics simulations are used to explore the
      folding of a signal peptide, a short but functionally independent domain at the N
      terminus of proteins. The peptide has been analyzed previously by NMR, and thus a
      solid reference state is provided with the experimental structure. Particular
      attention is paid to the role of water considered in full atomic detail.
      Different partial aspects in the folding process are quantified. The major group
      of obtained structures matches the NMR structure very closely. An important
      biological consequence is that in vivo folding of signal peptides seems to be
      possible within aqueous environments.

PMID- 17510962
TI  - Structural and biochemical characterization of inhibitor-1alpha.
AB  - Inhibitor-1alpha is one of the isoforms of human protein phosphatase inhibitor-1.
      It is a product of alternative splicing of inhibitor-1 gene and lacks 51 internal
      amino acids from residue 84 to 134 of inhibitor-1. Here we have characterized the
      structural and biochemical properties of inhibitor-1alpha. Structural analysis of
      recombinant inhibitor-1alpha by NMR spectroscopy revealed that inhibitor-1alpha
      adopts a predominantly random coil conformation. Excluding the region from
      residue 84 to 134 of inhibitor-1, the structural features of inhibitor-1 and
      inhibitor-1alpha are almost the same as each other. The IC(50) value of inhibitor
      1alpha in inhibition of Protein phosphatase-1 (PP1) is comparable to that of
      inhibitor-1, indicating that inhibitor-1alpha is a potent inhibitor of PP1 when
      Thr-35 is phosphorylated by PKA. For phosphorylation by PKA and dephosphorylation
      by protein phosphatase-1, -2A, and -2B, the measured kinetic parameters of
      inhibitor-1alpha are very close to those of inhibitor-1. Taken together, these
      results suggest that inhibitor-1alpha preserves the structure of inhibitor-1, the
      PP1 inhibitory activity and the functional specificities toward phosphorylation
      by PKA and dephosphorylation by protein phosphatase-1, -2A, and -2B.

PMID- 17510963
TI  - Constructing ensembles of flexible fragments in native proteins by iterative
      stochastic elimination is relevant to protein-protein interfaces.
AB  - We investigate the extent to which ensembles of flexible fragments (FF),
      generated by our loop conformational search method, include conformations that
      are near experimental and reflect conformational changes that these FFs undergo
      when binary protein-protein complexes are formed. Twenty-eight FFs, which are
      located in protein-protein interfaces and have different conformations in the
      bound structure (BS) and unbound structure (UbS) were extracted. The
      conformational space of these fragments in the BS and UbS was explored with our
      method which is based on the iterative stochastic elimination (ISE) algorithm.
      Conformational search of BSs generated bound ensembles and conformational search
      of UbSs produced unbound ensembles. ISE samples conformations near experimental
      (less than 1.05 A root mean square deviation, RMSD) for 51 out of the 56 examined
      fragments in the bound and unbound ensembles. In 14 out of the 28 unbound
      fragments, it also samples conformations within 1.05 A from the BS in the unbound
      ensemble. Sampling the bound conformation in the unbound ensemble demonstrates
      the potential biological relevance of the predicted ensemble. The 10 lowest
      energy conformations are the best choice for docking experiments, compared with
      any other 10 conformations of the ensembles. We conclude that generating
      conformational ensembles for FFs with ISE is relevant to FF conformations in the
      UbS and BS. Forming ensembles of the isolated proteins with our method prior to
      docking represents more comprehensively their inherent flexibility and is
      expected to improve docking experiments compared with results obtained by docking
      only UbSs.

PMID- 17510965
TI  - Using molecular dynamics to map interaction networks in an aminoacyl-tRNA
      synthetase.
AB  - Long-range functional communication is a hallmark of many enzymes that display
      allostery, or action-at-a-distance. Many aminoacyl-tRNA synthetases can be
      considered allosteric, in that their trinucleotide anticodons bind the enzyme at
      a site removed from their catalytic domains. Such is the case with E. coli
      methionyl-tRNA synthase (MetRS), which recognizes its cognate anticodon using a
      conserved tryptophan residue 50 A away from the site of tRNA aminoacylation. The
      lack of details regarding how MetRS and tRNA(Met) interact has limited efforts to
      deconvolute the long-range communication that occurs in this system. We have used
      molecular dynamics simulations to evaluate the mobility of wild-type MetRS and a
      Trp-461 variant shown previously by experiment to be deficient in tRNA
      aminoacylation. The simulations reveal that MetRS has significant mobility,
      particularly at structural motifs known to be involved in catalysis. Correlated
      motions are observed between residues in distant structural motifs, including the
      active site, zinc binding motif, and anticodon binding domain. Both mobility and
      correlated motions decrease significantly but not uniformly upon substitution at
      Trp-461. Mobility of some residues is essentially abolished upon removal of Trp
      461, despite being tens of Angstroms away from the site of mutation and solvent
      exposed. This conserved residue does not simply participate in anticodon binding,
      as demonstrated experimentally, but appears to mediate the protein's distribution
      of structural ensembles. Finally, simulations of MetRS indicate that the ligand
      free protein samples conformations similar to those observed in crystal
      structures with substrates and substrate analogs bound. Thus, there are low
      energetic barriers for MetRS to achieve the substrate-bound conformations
      previously determined by structural methods.

PMID- 17510964
TI  - The crystal structure of the secreted aspartic proteinase 3 from Candida albicans
      and its complex with pepstatin A.
AB  - The family of secreted aspartic proteinases (Sap) encoded by 10 SAP genes is an
      important virulence factor during Candida albicans (C. albicans) infections.
      Antagonists to Saps could be envisioned to help prevent or treat candidosis in
      immunocompromised patients. The knowledge of several Sap structures is crucial
      for inhibitor design; only the structure of Sap2 is known. We report the 1.9 and
      2.2 A resolution X-ray crystal structures of Sap3 in a stable complex with
      pepstatin A and in the absence of an inhibitor, shedding further light on the
      enzyme inhibitor binding. Inhibitor binding causes active site closure by the
      movement of a flap segment. Comparison of the structures of Sap3 and Sap2
      identifies elements responsible for the specificity of each isoenzyme.

PMID- 17510966
TI  - Modeling and analysis of molecularinteraction between Smurf1-WW2 domain and
      various isoforms of LIM mineralization protein.
AB  - LIM Mineralization Protein-1 (LMP-1) has been cloned and shown to be
      osteoinductive. Our efforts to understand the mode of action of LMP-1 led to the
      determination that LMP-1 interacts with Smad Ubiquitin Regulatory Factor-1
      (Smurf1). Smurf1 targets osteogenic Smads, Smad1/5, for ubiquitin-mediated
      proteasomal degradation. Smurf1 interaction with LMP-1 or Smads is based on the
      presence of unique WW-domain interacting motif in these target molecules. By
      performing site-directed mutagenesis and binding studies in vitro on purified
      recombinant proteins, we identified a specific motif within the osteogenic region
      of several LMP isoforms that is necessary for Smurf1 interaction. Similarly, we
      have identified that the WW2 domain of Smurf1 is necessary for target protein
      interaction. Here, we present a homology-based modeling of the Smurf1 WW2 domain
      and its interacting motif of LMP-1. We performed computational docking of the
      interacting domains in Smurf1 and LMPs to identify the key amino acid residues
      involved in their binding regions. In support of the computational predictions,
      we also present biochemical evidence supporting the hypothesis that the physical
      interaction of Smurf1 and osteoinductive forms of LMP may prevent Smurf1 from
      targeting osteogenic Smads by ubiquitin-mediated proteasomal degradation.

PMID- 17510967
TI  - Intrinsic disorder in yeast transcriptional regulatory network.
AB  - Intrinsic disorder has been shown to be important in mediating protein-protein
      and protein-DNA interactions. Proteins involved in regulatory functions are
      particularly enriched in intrinsic disorder. In this study we explored the role
      of intrinsic disorder in transcriptional regulatory network of yeast. Using
      disorder prediction programs we show that transcription factors (TFs) regulating
      large number of targets (transcriptional hubs) have significantly increased
      intrinsic disorder, though targets regulated by multiple TFs did not show
      increased intrinsic disorder. Intrinsic disorder may allow these transcriptional
      hubs to bind to diverse promoter regions of their targets in different contexts,
      and may also allow complex regulatory control of transcriptional hubs that are
      involved in coordinating different cellular processes.

PMID- 17510968
TI  - Crystal structure of a cyanobacterial sucrose-phosphatase in complex with glucose
      containing disaccharides.

PMID- 17510969
TI  - Fold recognition by concurrent use of solvent accessibility and residue depth.
AB  - Recognizing the structural similarity without significant sequence identity
      (called fold recognition) is the key for bridging the gap between the number of
      known protein sequences and the number of structures solved. Previously, we
      developed a fold-recognition method called SP(3) which combines sequence-derived
      sequence profiles, secondary-structure profiles and residue-depth dependent,
      structure-derived sequence profiles. The use of residue-depth-dependent profiles
      makes SP(3) one of the best automatic predictors in CASP 6. Because residue depth
      (RD) and solvent accessible surface area (solvent accessibility) are
      complementary in describing the exposure of a residue to solvent, we test whether
      or not incorporation of solvent-accessibility profiles into SP(3) could further
      increase the accuracy of fold recognition. The resulting method, called SP(4),
      was tested in SALIGN benchmark for alignment accuracy and Lindahl, LiveBench 8
      and CASP7 blind prediction for fold recognition sensitivity and model-structure
      accuracy. For remote homologs, SP(4) is found to consistently improve over SP(3)
      in the accuracy of sequence alignment and predicted structural models as well as
      in the sensitivity of fold recognition. Our result suggests that RD and solvent
      accessibility can be used concurrently for improving the accuracy and sensitivity
      of fold recognition. The SP(4) server and its local usage package are available
      on http://sparks.informatics.iupui.edu/SP4.

PMID- 17510970
TI  - Differential prognostic impact of comorbidity in head and neck cancer.
AB  - BACKGROUND: The aim was to investigate how the effect of comorbid illnesses on
      survival is modified by other prognostic factors in head and neck cancer.
      METHODS: A population-based retrospective cohort study involved 221 patients
      residing in 1 primary health care district (population about 700,000) in whom
      head and neck carcinoma was diagnosed between January 1, 1986, and December 31,
      1996. Data on clinical characteristics and survival were obtained from patient
      charts. Comorbidity was classified according to Charlson score. RESULTS: At 3
      years, the risk of death was significantly higher among the patients with high
      comorbidity status (score 3 or higher) (adjusted hazard ratio 2.1, 95% confidence
      interval 1.2-3.7). The excess risk associated with comorbidity, however, was
      confined to the subjects aged under 65 years and those with tongue or laryngeal
      tumors or stage I-II cancer. CONCLUSION: To assess the prognostic significance of
      comorbidity for an individual patient with head and neck cancer, age, tumor site,
      and cancer stage must be considered.

PMID- 17510971
TI  - Quality of life and voice in patients after laser cordectomy for Tis and T1
      glottic carcinomas.
AB  - BACKGROUND: Laser cordectomy is gaining popularity for treatment of early glottic
      carcinoma, but little is known about vocal and quality of life (QOL) outcomes as
      a function of extent of resection. We prospectively examined QOL and vocal
      function of patients with carcinoma in situ (Tis) or T1 glottic carcinomas after
      laser cordectomy. METHODS: Patients (n = 75) were grouped into those who
      underwent unilateral subepithelial or subligamental resection (group A, n = 45);
      those who underwent unilateral transmuscular or total cordectomy (group B, n =
      17); and those who underwent extended or bilateral cordectomy including the
      anterior commissure (group C, n = 19). The European Organization for Research and
      Treatment of Cancer head and neck cancer specific module (QLQ-H&N35), voice
      handicap index (VHI), and objective vocal function were examined before and 1
      year after cordectomy and compared among the groups. RESULTS: No major
      complications were encountered, but local recurrence occurred in 10 patients,
      with group C showing the highest rate (6/19, 31.6%). Patient-reported speech and
      social contact scores of QOL questionnaire and VHI scores after surgery were
      higher in groups B and C than in group A (p < .05). The scores and perceptual and
      acoustic data were generally improved in all groups after surgery, but were
      statistically significant only in group A (p < .03). CONCLUSION: Our data suggest
      that early glottic cancers with a limited extent and infiltration depth have
      improved outcomes, both oncologically and functionally, compared to those lesions
      requiring extensive laser resection.

PMID- 17510972
TI  - Effects of IFI16 overexpression on the growth and doxorubicin sensitivity of head
      and neck squamous cell carcinoma-derived cell lines.
AB  - BACKGROUND: In a previous analysis of head and neck squamous cell carcinomas
      (HNSCCs), we showed that the levels of the interferon-inducible protein IFI16
      inversely correlate with cancer grade. In this study, we further evaluate the
      molecular role of IFI16 in the development of HNSCCs. METHODS: The effect of
      IFI16 expression was evaluated by its retroviral restoration in an IFI16-negative
      HNSCC-derived cell line, HNO136. Growth rate and soft agar colony formation were
      evaluated. The effect of IFI16 restoration in cells exposed to doxorubicin was
      also analyzed. RESULTS: IFI16 restoration resulted in the inhibition of both cell
      growth and in vitro transforming activity and increased doxorubicin-induced cell
      death by accumulating the cells at the G2/M phase. CONCLUSION: In agreement with
      our previous in vivo data, IFI16 appears to be involved in maintaining the normal
      growth of epithelial cells, whereas its downregulation may contribute to
      uncontrolled cell proliferation and tumorigenesis.

PMID- 17510973
TI  - The impact of chronic illnesses on the use and effectiveness of adjuvant
      chemotherapy for colon cancer.
AB  - BACKGROUND: It is unclear how noncancer conditions affect the use or
      effectiveness of adjuvant therapy among older patients with colon cancer.
      METHODS: The authors conducted a cohort study of older patients with stage III
      colon cancer who were diagnosed from 1993 to 1999 in the Surveillance,
      Epidemiology, and End Results-Medicare database. The correlations between receipt
      of adjuvant chemotherapy and heart failure, diabetes, and chronic obstructive
      pulmonary disease (COPD) were assessed. Multivariable regression analysis was
      used to assess the risk of death and hospitalization as a function of treatment
      and comorbidity status. RESULTS: The study sample consisted of 5330 patients
      (median age, 76 years). The use of adjuvant therapy was related significantly to
      heart failure (36.2% vs 64.9% of patients with vs without heart failure,
      respectively; adjusted odds ratio [OR], 0.49; 95% confidence interval [95% CI],
      0.40-0.60). More moderate correlations were observed for COPD (OR, 0.83; 95% CI,
      0.70-0.99) and diabetes (OR, 0.81; 95% CI, 0.68-0.97). Among patients who had
      heart failure, the 5-year survival was significantly higher among those who
      received adjuvant chemotherapy (adjusted 5-year survival rate, 43%; 95% CI, 40
      47%) than among those who did not receive adjuvant chemotherapy (30%; 95% CI, 27
      34%). Among patients without heart failure, the 5-year survival estimates among
      treated and untreated patients were 54% (95% CI, 52-56%) and 41% (95% CI, 38
      44%), respectively. The probability of all-cause, condition-specific, or toxicity
      related hospitalization associated with adjuvant therapy was not altered by the
      presence of any of the 3 conditions. CONCLUSIONS: Although chronic conditions
      appeared to be a strong barrier to the receipt of adjuvant chemotherapy, adjuvant
      therapy appeared to provide a significant survival benefit to patients who had
      colon cancer with the conditions studied.

PMID- 17510974
TI  - Differential inductions of small heat shock protein 27 and 1-Cys peroxiredoxin in
      reactive astrocytes in sulfatide-deficient mouse spinal cord.
AB  - In myelinated fibers, various interactions among axons, oligodendrocytes, and
      astrocytes are present, particularly around the node of Ranvier. In the present
      study, we examined the protein composition of cerebroside sulfotransferase
      knockout (CST KO) mouse spinal cord by two-dimensional gel electrophoresis to
      examine the molecular changes resulting from the disruption of paranodal
      junctions in addition to the sulfatide-deficient condition. Interestingly, heat
      shock protein 27 (Hsp27) and 1-cys peroxiredoxin (1-Cys Prx) were both elevated
      in CST KO mice. Hsp27 was increased specifically in reactive astrocytes in the
      white matter, and the elevation was well correlated to the progression of
      neurologic symptoms. In contrast, 1-Cys Prx was elevated both in white and gray
      matter astrocytes in CST KO mice. These results suggest that astrocytes do not
      always respond stereotypically, as they display differences in their activation
      in these two regions. To determine whether these changes are specific to the
      sulfatide-deficient condition, spinal cords from CST KO mice and the
      hypomyelinating mutant shiverer mice were compared. The same distribution
      patterns of Hsp27 and 1-Cys Prx were found in reactive astrocytes in both CST KO
      and shiverer mice, suggesting that paranodal disruption with progressive nodal
      changes may underlie the similar reaction of white matter astrocytes. In
      contrast, CST KO and shiverer mice showed distinctly different localization
      patterns of connexin 43 and connexin 47, suggesting that intercellular
      communication between astrocytes and oligodendrocytes was different in these
      mutants. These results suggest that astrocytes may respond differentially to
      individual white matter abnormalities and may modulate specific axonal functions.

PMID- 17510975
TI  - Metabolomic investigation of CLN6 neuronal ceroid lipofuscinosis in affected
      South Hampshire sheep.
AB  - The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are a group of fatal
      inherited neurodegenerative diseases in humans and animals distinguished by a
      common clinical pathology, characteristic storage body accumulation in cells, and
      gross brain atrophy. An (1)H NMR spectroscopy- and GC-MS-based metabolomic
      investigation of changes in the cerebellum, frontal and occipital lobes, and
      cerebrospinal fluid (CSF) of CLN6 NCL affected South Hampshire sheep charted
      changes from the preclinical state to advanced disease. Glutamine and succinate
      concentrations increased in all brain regions in affected sheep relative to
      controls, whereas concentrations of aspartate, acetate, glutamate, N-acetyl
      aspartate (NAA), and gamma-aminobutyric acid (GABA) decreased. Changes in the
      concentrations of inositols, NAA, and GABA were consistent with glial cell
      activation and neurodegeneration beginning in the frontal and occipital lobes, in
      agreement with previous histopathological data. Further metabolic deficits were
      defined in all regions at earlier time points, including the cerebellum, where
      very little neurological degeneration has been reported. Biochemical
      abnormalities in the CSF of affected sheep at 18-31 months include relative
      increases in lactate, acetate, tyrosine, and creatine/creatinine concentrations
      and decreases in myo- and scyllo-inositol and citrate concentrations. The changes
      detected in the CSF and brain tissue mirrored those previously apparent in NCL
      mouse models, suggesting that they are common to all NCLs. However, the changes
      in glutamate and glutamine concentrations in CSF occurred after clinical disease,
      indicating that any changes in glutamate/glutamine cycling occur as a consequence
      of the primary deficits associated with the NCLs.

PMID- 17510976
TI  - Immunohistochemical distribution of glucose-dependent insulinotropic polypeptide
      in the adult rat brain.
AB  - We have previously demonstrated that glucose-dependent insulinotropic polypeptide
      (GIP; gastric inhibitory polypeptide) is present in the adult rat hippocampus.
      This finding leads to the conclusion that all members of the secretin-glucagon
      family of gastrointestinal regulatory polypeptides can be found in the brain. To
      investigate the localization of GIP-producing cells, we used immunohistochemistry
      on sections of the adult rat brain. High levels of GIP immunoreactivity were
      observed in the olfactory bulb, hippocampus, and Purkinje cells in the
      cerebellum. Moreover, a moderate but distinct GIP immunoreactivity was observed
      in the cerebral cortex, amygdala, substantia nigra, and lateral septal nucleus as
      well as in several nuclei in the thalamus, hypothalamus, and brainstem. GIP
      immunoreactivity was frequently found to colocalize with the neuronal marker NeuN
      but never with the glial marker glial fibrillary acidic protein. Thus, GIP
      appears to be mainly neuronal to its distribution. This widespread distribution
      of GIP-immunoreactive cells suggests the involvement of GIP in various neuronal
      functions and suggests that GIP may act as a neurotransmitter or neuromodulator.
      This is the first characterization of the anatomical distribution of GIP
      immunoreactive cells in the rat brain providing an anatomical framework for
      future investigations regarding the functions of GIP in the central nervous
      system.

PMID- 17510977
TI  - Amyloid beta protein-related death-inducing protein induces G2/M arrest:
      Implications for neurodegeneration in Alzheimer's disease.
AB  - Amyloid beta protein (Abeta)-related death-inducing protein (AB-DIP) is a novel
      Abeta binding protein expressed ubiquitously. Here we demonstrate that
      overexpression of AB-DIP in SH-SY5Y neuroblastoma cells causes G2/M arrest. By
      deletion mutant analysis, we have identified the minimal region within AB-DIP
      required for G2/M arrest. We have also shown that microtubule-interfering agents
      (MIAs) such as nocodazole, vinblastine, paclitaxel, and vincristine, known to
      arrest cells at G2/M, also phosphorylate AB-DIP. However, etoposide, which causes
      genotoxic stress; tunicamycin, an ER stress inducer; and rotenone, which causes
      mitochondrial damage, fail to phosphorylate AB-DIP, implying that phosphorylation
      of AB-DIP is specific to microtubule-disruption-induced G2/M arrest. By using
      different classes of kinase inhibitors, we also demonstrate that a putative
      tyrosine kinase phosphorylates AB-DIP. Mono- or multisite mutations of tyrosine
      or serine/threonine residues confirmed that mutation of tyrosine residues but not
      serine/threonine residues greatly reduces nocodazole-induced phosphorylation of
      AB-DIP. Furthermore, phosphorylation of AB-DIP can be induced in MCF-7 cells that
      lack functional p53, suggesting that AB-DIP phosphorylation is independent of
      p53. Mounting experimental evidence continues to support the role of cell cycle
      abnormalities in the pathogenesis of Alzheimer's disease, and our results suggest
      that AB-DIP might provide a mechanistic link between microtubule disruption,
      mitotic abnormalities, neuronal dysfunction, and death. Therefore, interfering
      with AB-DIP may have therapeutic applications in conditions such as Alzheimer's
      disease, in which microtubule disruption and mitotic abnormalities have been
      suggested to play a pathological role.

PMID- 17510978
TI  - Beta-amyloid (25-35) enhances lipid metabolism and protein ubiquitination in
      cultured neurons.
AB  - We investigated the effect of beta-amyloid (Abeta) (25-35), a cytotoxic fragment
      of Abeta peptide, on lipid metabolism and protein ubiquitination in cultured rat
      hippocampal neurons. After treatment with Abeta under conditions leading to
      apoptotis, as assessed by caspase activity assay, the total cell mass of lipids
      changed following a biphasic behavior, with an increase that reached a maximum
      after 16 hr of treatment, followed by a decrease. The increase at 16 hr was 15.3%
      in the case of phospholipids and 103.0% in the case of gangliosides and was due
      to enhanced biosynthesis as confirmed by increase of radioactivity incorporation
      (phospholipids +52.0%, gangliosides +193.1%) in cells fed with tritiated palmitic
      acid. No change with respect to cholesterol was observed. Strikingly, under these
      conditions, the ubiquitination state of cell proteins strongly increased. These
      effects were not observed with the (35-25) reverse sequence peptide. Similarly to
      Abeta, lactacystin treatment increased lipid synthesis and protein
      ubiquitination; only lactacystin, and not Abeta, induced a strong decrease of
      proteasome chimotrypsin activity. These results suggest that Abeta enhances
      protein ubiquitination, without inhibiting proteasomal activity, and lipid
      synthesis. These results may shed new light on the mechanisms of Abeta toxicity.

PMID- 17510979
TI  - Oxidative damage in mild cognitive impairment and early Alzheimer's disease.
AB  - Increasing evidence supports a role for oxidative damage in the pathogenesis of
      Alzheimer's disease (AD). Multiple studies show significantly increased levels of
      lipid peroxidation and protein, DNA, and RNA oxidation in vulnerable regions of
      the brain of patients with late-stage AD (LAD). More recent studies of patients
      with amnestic mild cognitive impairment (MCI), the earliest clinical
      manifestation of AD, show similar patterns of oxidative damage. These
      observations suggest that oxidative damage to critical biomolecules occurs early
      in the pathogenesis of AD and precedes pronounced neuropathologic alterations.
      Because oxidative damage begins early in the progress of the disease, it
      represents a potential therapeutic target for slowing the onset and progression
      of AD.

PMID- 17510981
TI  - Chemokine ligand 2 (CCL2) induces migration and differentiation of subventricular
      zone cells after stroke.
AB  - Ischemic stroke stimulates neurogenesis in the adult rodent brain. The molecules
      that mediate stroke-induced neurogenesis have not been fully investigated. Using
      a microarray containing 113 known genes associated with angiogenesis, we analyzed
      transcriptional profiles in subventricular zone (SVZ) tissue and in cultured
      neural progenitor cells isolated from the SVZ of adult mice subjected to middle
      cerebral artery occlusion (MCAo). Among the genes most robustly up-regulated by
      MCAo were chemokine ligand 2 (CCL2) and chemokine ligand 10 (CXCL10). Consistent
      with the mRNA data, immunofluorescent staining revealed that MCAo substantially
      increased the number of CCL2-positive cells in the ipsilateral SVZ and that CCL2
      positive cells were positive for both glial fibrillary acidic protein (GFAP) and
      nestin. In vitro studies showed that incubation of neural progenitor cells with
      recombinant human CCL2 substantially increased the number of Tuj1-positive cells
      dose dependently compared with the number in the control group, indicating that
      CCL2 promotes neuronal differentiation. Blockage of CCL2 with a neutralized
      antibody against CCL2 abolished the effects of CCL2 on neural progenitor cell
      migration and differentiation. Treatment of neural progenitor cells with CCL2 did
      not alter the number of BrdU cells and the number of apoptotic cells compared
      with those in the control group, suggesting that CCL2 does not affect neural
      progenitor cell proliferation and cell survival. These data demonstrate that in
      addition to its role in cell motility, CCL2 plays an important role in neuronal
      differentiation.

PMID- 17510980
TI  - Regulatory factor X4 variant 3: a transcription factor involved in brain
      development and disease.
AB  - Regulatory factor X4 variant 3 (RFX4_v3) is a recently identified transcription
      factor specifically expressed in the brain. Gene disruption in mice demonstrated
      that interruption of a single allele (heterozygous, +/-) prevented formation of
      the subcommissural organ (SCO), resulting in congenital hydrocephalus, whereas
      interruption of two alleles (homozygous, -/-) caused fatal failure of dorsal
      midline brain structure formation. These mutagenesis studies implicated RFX4_v3
      in early brain development as well as the genesis of the SCO. Rfx4_v3 deficiency
      presumably causes abnormalities in brain by altering the expression levels of
      many genes that are crucial for brain morphogenesis, such as the signaling
      components in the Wnt, bone morphogenetic protein, and retinoic acid pathways.
      RFX4_v3 might affect these critical signaling pathways in brain development.
      Cx3cl1, a chemokine gene highly expressed in brain, was identified as a direct
      target for RFX4_v3, indicating that RFX4_v3 possesses trans-acting activity to
      stimulate gene expression. Rfx4_v3 is highly expressed in the suprachiasmatic
      nucleus and might be involved in regulating the circadian clock. One haplotype in
      RFX4_v3 gene is linked to a higher risk of bipolar disorder, suggesting that this
      protein might contribute to the pathogenesis of the disease. This Mini-Review
      describes our current knowledge about RFX4_v3, an important protein that appears
      to be involved in many aspects of brain development and disease.

PMID- 17510982
TI  - Peroxynitrite-mediated oxidative damage to brain mitochondria: Protective effects
      of peroxynitrite scavengers.
AB  - Peroxynitrite-mediated oxidative damage has been implicated in brain
      mitochondrial respiratory dysfunction after traumatic brain injury (TBI), which
      precedes the onset of neuronal loss. The aim of this study was to investigate the
      detrimental effects of the peroxynitrite donor SIN-1 (3-morpholinosydnonimine) on
      isolated brain mitochondria and to screen penicillamine, a stoichiometric (1:1)
      peroxynitrite-scavenging agent, and tempol, a catalytic scavenger of
      peroxynitrite-derived radicals, as antioxidant mitochondrial protectants.
      Exposure of the isolated mitochondria to SIN-1 caused a significant dose
      dependent decrease in the respiratory control ratio and was accompanied by a
      significant increase in state II respiration, followed by significant decreases
      (P < 0.05) in states III and V. These functional alterations occurred together
      with significant increases in mitochondrial protein carbonyl (PC), lipid
      peroxidation-related 4-hydroxynonenal (4-HNE), and 3-nitrotyrosine (3-NT)
      content. Penicillamine hydrochloride (10 microM) partially but significantly (P <
      0.05) protected against SIN-1-induced decreases in states III and V. However, a
      2.5 microM concentration of tempol was able to significantly antagonize a 4-fold
      molar excess (10 microM) concentration of SIN-1 as effectively as were higher
      tempol concentrations, consistent with the likelihood that tempol works by a
      catalytic mechanism. The protection of mitochondrial respiration by penicillamine
      and tempol occurred in parallel with attenuation of PC, 4-HNE, and 3-NT. These
      results indicate that SIN-1 causes mitochondrial oxidative damage and complex I
      dysfunction and that antioxidant compounds that target either peroxynitrite or
      its radicals may be effective mitochondrial protectants in the treatment of
      neural injury.

PMID- 17510984
TI  - Rhizobialide: a new stearolactone produced by Mesorhizobium sp. CCNWGX022, a
      rhizobial endophyte from Glycyrrhiza uralensis.
AB  - The endophytic strain Mesorhizobium sp. CCNWGX022 was isolated from licorice
      (Glycyrrhiza uralensis Fisch.) grown in the arid and semi-arid regions of
      Northwest China. The new stearic acid derived gamma-lactone 1, named rhizobialide
      (= (5S)-4,5-dihydro-5-(8-oxotetradecyl)furan-2(3H)-one), was isolated from the
      petroleum-ether extract of the fermentation broth of this strain. The structure
      of 1 was elucidated on the basis of spectroscopic and mass-spectrometric
      analysis. This is the first report of this type of compound from rhizobia.

PMID- 17510985
TI  - Secondary metabolites from endophytic Streptomyces sp. Lz531.
AB  - From the branch tissue of Maytenus hookeri, the endophytic strain Lz531 was
      isolated, and determined to belong to Streptomyces, according to its 16S rRNA
      sequence. From the extracts of the fermentation broth of Streptomyces sp. Lz531,
      two new and four known compounds were isolated. The two new compounds were
      identified as cyclo(L-Pro-L-Val-L-Val) (1) and 13-methyl-N-(2
      phenylethyl)tetradecanamide (2).

PMID- 17510983
TI  - Evidence that nucleocytoplasmic Olig2 translocation mediates brain-injury-induced
      differentiation of glial precursors to astrocytes.
AB  - The mechanisms by which neural and glial progenitor cells in the adult brain
      respond to tissue injury are unknown. We studied the responses of these cells to
      stab wound injury in rats and in two transgenic mouse models in which Y/GFP is
      driven either by Sox2 (a neural stem cell marker) or by Talpha-1 (which marks
      newly born neurons). The response of neural progenitors was low in all
      nonneurogenic regions, and no neurogenesis occurred at the injury site. Glial
      progenitors expressing Olig2 and NG2 showed the greatest response. The appearance
      of these progenitors preceded the appearance of reactive astrocytes.
      Surprisingly, we found evidence of the translocation of the transcription factor
      Olig2 into cytoplasm in the first week after injury, a mechanism that is known to
      mediate the differentiation of astrocytes during brain development. Translocation
      of Olig2, down-regulation of NG2, and increased glial fibrillary acidic protein
      expression were recapitulated in vitro after exposure of glial progenitors to
      serum components or bone morphogentic protein by up-regulation of Notch-1. The
      glial differentiation and Olig2 translocation could be blocked by inhibition of
      Notch-1 with the gamma-secretase inhibitor DAPT. Together, these data indicate
      that the prompt maturation of numerous Olig2(+) glial progenitors to astrocytes
      underlies the repair process after a traumatic injury. In contrast, neural stem
      cells and neuronal progenitor cells appear to play only a minor role in the
      injured adult CNS.

PMID- 17510986
TI  - Variability of the needle essential oils of Pinus heldreichii from different
      populations in Montenegro and Serbia.
AB  - The essential-oil compositions of Pinus heldreichii Christ. from Montenegro and
      Serbia are reported at the population level. Whitebark pine is a sub-endemic high
      mountain Balkan pine relict of an anthropogenically reduced area, with large
      morphological diversity and insufficiently clear taxonomic position. In the pine
      needle terpene profile from three populations from Montenegro, and one from
      Serbia, 101 compounds were detected, 72 of which could be identified (Table 3).
      The dominant constituents are limonene (26.3%), alpha-pinene (17.5%), germacrene
      D (13.5%), and beta-caryophyllene (10.4%), comprising ca. 67.7% of the essential
      oil. Medium-to-high contents (0.5-10%) of the following 16 additional components
      were found: beta-pinene, beta-myrcene, alpha-humulene, delta-cadinene, alpha
      muurolene, (E)-hex-2-enal, beta-gurjunene, gamma-muurolene, isopimarol, camphene,
      gamma-cadinene, aromadendrene, beta-bisabolene, trans-beta-farnesene, alpha
      cadinene, and (Z)-hex-3-en-1-ol. The similarity of the populations and the within
      population variability was visualized by principle-component analysis (PCA) of
      eleven selected terpenes in 97 tree samples. Cluster and genetic analyses suggest
      closest connection between the two spatially most-distant populations I
      (Montenegro) and IV (Serbia). Based on the profile of the main sesquiterpene
      components, the studied populations from Montenegro and Serbia are more similar
      to the populations from Greece and the Central Balkan peninsula (Bosnia and
      Serbia-Kosovo) than to those on the furthest eastern margin of their natural
      range (Bulgaria).

PMID- 17510987
TI  - Two new protease-inhibiting glycosphingolipids from Buddleja crispa.
AB  - Crispins A (1) and B (2), two new glycosphingolipids, were isolated from the
      whole plant Buddleja crispa, along with three known compounds: alpha-amyrin,
      linoleic acid, and stigmasterol. Their structures were elucidated by chemical and
      spectroscopic techniques. Both 1 and 2 showed significant inhibitory activity
      against alpha-chymotrypsin in a concentration-dependent manner.

PMID- 17510988
TI  - Surface-plasmon-enhanced fluorescence spectroscopy for DNA detection using
      fluorescently labeled PNA as "DNA indicator".

PMID- 17510989
TI  - Helical arrangement of interstrand stacked pyrenes in a DNA framework.

PMID- 17510990
TI  - Determination of the geometry change of the phenol dimer upon electronic
      excitation.
AB  - The change of the phenol dimer (PH2) structure upon electronic excitation is
      determined by a Franck-Condon analysis of the intensities in the fluorescence
      emission spectra obtained via excitation of seven different vibronic bands. A
      total of 547 emission band intensities are fitted, together with the changes of
      rotational constants upon electronic excitation of fi ve isotopomers. These
      rotational constants are taken from previously published [Schmitt et al.
      ChemPhysChem 2006, 7, 1241-1249] high-resolution LIF measurements. The geometry
      change upon electronic excitation of the pipi* state of the donor moiety can be
      described by a strong shortening of the hydrogen bond, a shortening of the CO
      bond in the donor moiety, an overall symmetric expansion of the donor phenol
      ring, and a nearly unchanged acceptor moiety. The resulting geometry changes are
      interpreted on the basis of ab initio calculations.

PMID- 17510991
TI  - Robust, biomimetic polymer brush layers grown directly from a planar mica
      surface.

PMID- 17510992
TI  - Isolation, structure elucidation, and antioxidant evaluation of cydonioside A, an
      unusual terpenoid from the fruits of Cydonia vulgaris.
AB  - A novel terpenoid, cydonioside A (1), was isolated from the fruits of Cydonia
      vulgaris Pers. Its structure and relative configuration were elucidated on the
      basis of in-depth spectroscopic analyses, including 2D-NMR experiments as well as
      MM+ calculations. Compound 1 was assayed for its radical-scavenging activity
      towards the DPPH radical and the superoxide radical anion (O2*-), as well as for
      its overall antioxidant activity, as assessed by the formation of a
      phosphomolybdenum complex.

PMID- 17510993
TI  - Synthesis and antitumor evaluation of benzopsoralen analogues.
AB  - The synthesis of five new tetracyclic benzopsoralen analogues, compounds 2-6,
      with 9H-xanthen-9-one or 9H-carbazole frameworks, is described. Their inhibitory
      effects on the growth of three human tumor cell lines (MCF-7, SF-268, and NCI
      460) were evaluated, and discussed in terms of structure-activity relationship,
      taking into account both geometric and electronic features. Generally, the
      angular compounds showed significant biological activities, but the arrangement
      of functional groups also contributed to the overall activity.

PMID- 17510994
TI  - A functionalized 20-residue peptaibol derivative for nucleic acid delivery.
AB  - Based on the membrane-modifying peptaibol trichocellin-A-I (1) from Trichoderma
      viride, we designed a vehicle for the cellular delivery of antisense
      oligodeoxynucleotides by attaching a (Lys)10 stretch to the C-terminus of 1. The
      resulting transporter peptide 2, prepared by solid-phase synthesis using Fmoc
      protocol in combination with amino acid fluorides, was found to be mainly alpha
      helical in solution, in contrast to its precursors 1 and 3. The uptake of the
      complex formed between carrier 2 and a fluorescence-tagged oligonucleotide, i.e.,
      4, was studied at different charge ratios by confocal laser-scanning microscopy,
      using two different eukaryotic cell lines: mouse embryonal fibroblast (NIH3T3)
      and human lung carcinoma (A549) cells. Peptide 2 readily translocated 4 into the
      cytoplasms of NIH3T3 cells. However, the peptide/oligonucleotide complex was
      accumulated around the plasma membrane of the A549 cells.

PMID- 17510995
TI  - Cytotoxic cardenolides from Streptocaulon griffithii.
AB  - A new cardenolide, 3-O-(beta-glucopyranosyl)acovenosigenin A (1), was isolated
      from the roots of Streptocaulon griffithii, together with eight known
      cardenolides, compounds 2-9. All compounds showed significant in vitro inhibition
      of the proliferation of the human gastrointestinal cancer cell line HGC-27, with
      IC50 values in the range of ca. 20-564 nM, taxol being used as positive control.
      Compound 1 was also found to be strongly cytotoxic against other human tumor cell
      lines, including A549, MCF-7, and Hela cells.

PMID- 17510996
TI  - Oral administration of (11E)-13-oxo-15,16-dinorlabda-8(20),11-dien-19-oic acid
      strongly reduces photocarcinogenesis in mouse skin exposed to UV-B irradiation.
AB  - (11E)-13-Oxo-15,16-dinorlabda-8(20),11-dien-19-oic Acid (1), obtained either from
      the stem bark of Thuja standishii or readily prepared in larger quantities from
      the related constituent 2, was found to significantly reduce the formation of
      papilloma in an in vivo two-stage mouse-skin-carcinogenesis model. Carcinogenesis
      was initiated by skin exposure to UV-B irradiation and promoted by topical
      application of 12-O-tetradecanoylphorbol-13-acetate (TPA). Oral administration of
      1, starting one week before and ending one week after irradiation, exhibited
      remarkable effects. First, papilloma formation started two weeks later than in
      the control group (lacking 1). Second, the average number of skin papilloma after
      20 weeks was reduced by ca. 50% in the test group relative to the control.

PMID- 17510997
TI  - Seasonal variation of the chemical constituents of the essential oil of Santolina
      etrusca from Italy.
AB  - The seasonal variation of the essential oil, in terms of both yield and
      composition, of a population of Santolina etrusca (Asteraceae) is reported in
      detail for different aerial parts, including sterile branches, fertile branches,
      and capitula. The yields generally increased from November to June, and then
      decreased in August and September. The main constituents of the sterile branches
      were 1,8-cineole and viridiflorol. The oil from fertile branches was
      characterized by myrcene as principal compound, whereas the essential oil
      obtained from the capitula contained germacrene D as the main constituent.
      Several compounds, as identified by GC and GC/MS, were found to prevail during
      the cold season.

PMID- 17510998
TI  - Structures and biological properties of the chemical constituents from the genus
      Wedelia.

PMID- 17510999
TI  - Possible molecular evolution of biomembranes: from single-chain to double-chain
      lipids.
AB  - We have studied a possible evolution process permitting a 'primitive' membrane to
      evolve towards a membrane structure with an outer wall, similar to that of
      bacteria. We have investigated whether a polysaccharide bearing hydrophobic
      phytyl or cholesteryl chains coats giant vesicles made of single- or double-chain
      lipids. Phytyl-pullulan 5b was found to bind to the surface of vesicles made of
      either single- or double-chain lipids. In contrast, cholesteryl-pullulan 5a only
      coated the surface of vesicles made of double-chain lipids. These results
      indicate that there must be a close match between the size and shape of membrane
      constituents and the hydrophobic molecules to be inserted. This process could,
      thus, provide a selection mechanism of lipid-membrane constituents during the
      course of biomembrane evolution. The presence of the above 'hydrophobized'
      polysaccharides on the surface of different giant vesicles was identified by
      lectin binding. Both concanavalin A and annexin V were shown by fluorescence
      microscopy to bind spontaneously to vesicles made of double-chain lipids. Our
      experiments exemplify that self-organization of amphiphiles into closed vesicles
      in aqueous solution automatically leads to the coating of vesicles by
      'hydrophobized' polysaccharides, which then permit lectin binding. This is a
      possible mechanism for the evolution of primitive membranes towards 'proto
      cells'.

PMID- 17511000
TI  - Distribution of phenolic compounds in Middleeuropean taxa of the Achillea
      millefolium L. aggregate.
AB  - Achillea millefolium L. s.l. is a cytogenetically, morphologically, and
      chemically polymorphic aggregate. Besides the sesquiterpenes that possess
      chemotaxonomic relevance and mediate the antiphlogistic activity, the plant
      contains phenolic compounds such as dicaffeoylquinic acids and flavonoids causing
      choleretic and spasmolytic effects. To evaluate their contribution to the
      chemotaxonomy of European taxa of the A. millefolium group, we developed a SPE
      HPLC/UV method that allows quantification of the phenolic constituents in the
      different taxa. The investigated species displayed differences in the
      quantitative and qualitative composition of phenolic acids and flavonoids. Hence,
      they seem to be of chemotaxonomic significance, especially for the distinction of
      the diploid taxa. Combining the obtained results with the data of the
      sesquiterpene analyses gives a comprehensive insight into the distribution of
      those pharmacologically relevant plant constituents in the A. millefolium group.

PMID- 17511001
TI  - RNA interference tolerates 2'-fluoro modifications at the Argonaute2 cleavage
      site.
AB  - Short interfering RNA (siRNA) molecules with good gene-silencing properties are
      needed for drug development based on RNA interference (RNAi). An initial step in
      RNAi is the activation of the RNA-induced silencing complex RISC, which requires
      degradation of the sense strand of the siRNA duplex. Although various chemical
      modifications have been introduced to the antisense strand, modifications to the
      Argonaute2 (Ago2) cleavage site in the sense strand have, so far, not been
      described in detail. In this work, novel 2'-F-purine modifications were
      introduced to siRNAs, and their biological efficacies were tested in cells stably
      expressing human tartrate-resistant acid phosphatase (TRACP). A validated siRNA
      that contains both purine and pyrimidine nucleotides at the putative Ago2
      cleavage site was chemically modified to contain all possible combinations of 2'
      fluorinated 2'-deoxypurines and/or 2'-deoxypyrimidines in the antisense and/or
      sense strands. The capacity of 2'-F-modified siRNAs to knock down their target
      mRNA and protein was studied, together with monitoring siRNA toxicity. All 2'-F
      modified siRNAs resulted in target knockdown at nanomolar concentrations, despite
      their high thermal stability. These experiments provide the first evidence that
      RISC activation not only allows 2'-F modifications at the sense-strand cleavage
      site, but also increase the biological efficacy of modified siRNAs in vitro.

PMID- 17511002
TI  - Starch degradation by glucoamylase Glm from Saccharomycopsis fibuligera IFO 0111
      in the presence and absence of a commercial pullulanase.
AB  - This study describes the course of enzymatic hydrolysis of the native corn
      starches Maritena 100 and Maritena 300. Hydrolyses were carried out with
      glucoamylase Glm produced by Saccharomycopsis fibuligera IFO 0111, which degrades
      also native starch, with the purpose to substitute a two-step hydrolysis (amylase
      followed by glucoamylase) by a one-step process (glucoamylase only). Hydrolysis
      generally became more effective by adding the pullulanase Promozyme D, which
      cleaves alpha-1,6-glycosidic bonds more effectively than glucoamylase Glm does.
      The time course (kinetics) of hydrolysis was followed by determination of the
      glucose concentration and calculation of dextrose equivalents.

PMID- 17511003
TI  - Synthesis and cytotoxic evaluation of substituted urea derivatives as inhibitors
      of human-leukemia K562 cells.
AB  - A series of substituted urea derivatives, compounds 1-14, were synthesized and
      evaluated for their cytotoxic activities against the human-leukemia K562 cell
      line. Two structurally simple compounds, 7 and 12, both incorporating a
      morpholine ring, were found to be highly active, with IC50 values of ca. 0.25
      microM.

PMID- 17511004
TI  - Cytotoxic and apoptosis-inducing properties of auriculoside A in tumor cells.
AB  - The C21-steroidal glycoside auriculoside A (1), recently isolated from the roots
      of Cynanchum auriculatum, was found to inhibit the growth of several human tumor
      cell lines and to induce apoptosis in human breast cancer (MCF-7) cells. Compound
      1 was evaluated for its in vitro cytotoxicity against MCF-7, HO-8910, and Bel
      7402 cells, and for its in vivo antitumor effects on implanted sarcoma-180 (S180)
      tumors in mice. It showed significant, concentration-dependent inhibition of the
      cancer cells, both in vitro and in vivo. MCF-7 Cells exposed to 1 displayed
      typical morphological apoptosis characteristics such as cytoplasm contraction and
      nuclear-chromatin condensation. Flow-cytometric analysis showed that the MCF-7
      cell cycle was arrested at the G0/G1 phase. When treated with 40 microg/ml of 1
      for 24, 48, and 72 h, respectively, the apoptotic rates of the cells were ca. 5,
      8, and 18.5%, respectively.

PMID- 17511005
TI  - Three new sesquiterpenoids from the aerial parts of Homalomena occulta.
AB  - Three new eudesmane-type sesquiterpenoids, compounds 1-3, and eight known
      constituents, including mucrolidin (4), 1beta,4beta,7alpha-trihydroxyeudesmane
      (5), 1beta,4beta,6beta,11-tetrahydroxyeudesmane (6), oplodiol (7), bullatantriol
      (8), acetylbullatantriol (9), homalomenol (10), and maristeminol (11), were
      isolated from the aerial parts of Homalomena occulta. Their structures were
      determined by interpretation of spectroscopic and mass-spectrometric data, and
      their antimicrobial activities toward six different bacterial strains were
      tested. Most of the compounds showed weak antibacterial activities in an agar
      diffusion assay.

PMID- 17511006
TI  - Synthesis, cytotoxicity, and antitumor activity of lantadene-A congeners.
AB  - Five new derivatives of the pentacyclic triterpenoid lantadene A (= 22beta
      angeloyloxy-3-oxoolean-12-en-28-oic acid; 1) from the leaves of Lantana camara L.
      were synthesized, characterized, and screened for their cytotoxicities against
      four human cancer cell lines. The three most-potent compounds, i.e., 1, 4, and 6,
      with IC50 values in the range of ca. 20-29 microM, were further studied for their
      in vivo tumor-inhibitory potential upon oral administration in two-stage squamous
      cell carcinogenesis, using female Swiss albino mice, papilloma being induced by
      7,12-dimethylbenz[a]anthracene (DMBA), and promoted by 12-O-tetradecanoylphorbol
      13-acetate (TPA). The results are discussed in terms of structure-activity
      relationship.

PMID- 17511007
TI  - Cytotoxic prenylated phenolic compounds from the twig bark of Garcinia
      xanthochymus.
AB  - Three new hydroxylated xanthones with prenyl or geranyl substituents, compounds 1
      3, were isolated from the twig bark of Garcinia xanthochymus, along with the four
      known compounds 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone (4), 1,3,5,6
      tetrahydroxy-4,7,8-triprenylxanthone (5), garciniaxanthone E (6), and 6
      prenylapigenin (7). Their structures were elucidated by extensive spectroscopic
      analysis, including 1D- and 2D-NMR as well as HR-MS experiments. All compounds
      showed moderate cytotoxicities against breast cancer (MDA-MB-435S) and lung
      adenocarcinoma (A549) cell lines, but lacked antifungal activity against Candida
      albicans.

PMID- 17511008
TI  - Medicinal studies of dimeric phenols with multiple quaternary-ammonium pendant
      arms.
AB  - A series of biphenol-derived quaternary ammonium salts, originally developed as
      DNA-cross-linking agents, and carrying either two (i.e., 1) or four (i.e., 2) net
      positive charges, were investigated for their in vitro DNA-transcription- and
      acetylcholinesterase (AChE)-inhibitory activities. The effects of charge and type
      of linker between the two phenolic residues were systematically investigated.
      Several compounds showed good activities in both tests, which makes them
      potential lead candidates for drug design.

PMID- 17511009
TI  - A ferromagnetic mixed-valent Mn supertetrahedron: towards low-temperature
      magnetic refrigeration with molecular clusters.

PMID- 17511010
TI  - A major triterpenoid saponin from Gypsophila oldhamiana.
AB  - A new saponin, gypoldoside A (1), was isolated from the roots of Gypsophila
      oldhamiana. On the basis of in-depth NMR-spectroscopic and mass-spectrometric
      analysis, in combination with chemical evidence, its structure was established as
      3-O-{beta-D-galactopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-beta-D
      glucuronopyranosyl}quillaic acid 28-[alpha-L-arabinopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-
      >2)-beta-D-fucopyranosyl] ester. Compound 1 was found to be highly active against
      three different human cancer cell lines, with IC50 values in the low micromolar
      range.

PMID- 17511011
TI  - Benzoquinones from Ardisia japonica with inhibitory activity towards human
      protein tyrosine phosphatase 1B (PTP1B).
AB  - From the whole plant of Ardisia japonica, four [1,4]benzoquinones were isolated
      by means of bioassay-directed fractionation of the EtOH extract. Apart from the
      two known compounds maesanin (1) and its congener 2, two new benzoquinones, i.e.,
      5-ethoxy-2-hydroxy-3-[(10Z)-pentadec-10-en-1-yl][1,4]benzoquinone (3) and 5
      ethoxy-2-hydroxy-3-[(8Z)-tridec-8-en-1-yl][1,4]benzoquinone (4), were identified.
      All compounds showed significant in vitro bioactivities against the PTP1B enzyme,
      with IC50 values in the range of ca. 3-19 microM.

PMID- 17511012
TI  - Dibenzocyclooctane lignans from the stems of Kadsura induta and their antiviral
      effect on hepatitis B virus.
AB  - Two new dibenzocyclooctane lignans, kadsurindutins A (1) and B (2), were isolated
      from the stems of Kadsura induta, together with the known, structurally related
      lignans schisantherin L (3), schisantherin P (4), kadsulignan L (5), and
      neokadsuranin (6). Their structures and configurations were elucidated by
      spectroscopic methods (UV, ORD, CD, IR, 1D- and 2D-NMR) in combination with mass
      spectrometric (HR-MS) techniques. Compounds 1, 5, and 6 showed in vitro antiviral
      effects on hepatitis B virus.

PMID- 17511013
TI  - Specific UV photodissociation of tyrosyl-containing peptides in multistage mass
      spectrometry.
AB  - UV photodissociation (UVPD) at 262 nm has been carried out on protonated tyrosyl
      containing peptides formed by trypsin digestion of apo-transferrin. Under UVPD,
      the main event is the fragmentation of the C(alpha)-C(beta) bond of the tyrosyl
      residues leading to a radical ion 107 Da below the precursor ion. The
      dissociation rate of this specific cleavage appears to be strongly dependent on
      the peptide sequence and is more prominent on the singly protonated species than
      on the doubly protonated state. The fragmentation spectra resulting from
      collisional activation of the protonated even-electron native peptides and of the
      odd-electron radical species prepared by UVPD are dominated by y-type backbone
      cleavages. A comparison of their respective y-ion pattern shows complementarities
      since the combination of both increases the sequence coverage of the peptide
      sequence. The specific detection of the neutral loss of 107 Da from peptides
      witnesses the content of at least one tyrosyl residue and, though preliminary, is
      proposed as a potential new filtering strategy during protein database searching.

PMID- 17511014
TI  - Quantitation of phenylalanine and its trans-cinnamic, benzoic and hippuric acid
      metabolites in biological fluids in a single GC-MS analysis.
AB  - We describe a sensitive, simple and convenient stable isotope dilution assay
      developed to study endogenous metabolism of administered stable isotope-labeled
      phenylalanine (Phe) in phenylketonuric (PKU) mice treated experimentally with
      phenylalanine ammonia lyase (PAL). Mouse urine and plasma containing endogenous
      and administered labeled Phe together with internal standard Phe bearing a
      different pattern of labeling are converted by in situ diazotization to 2-chloro
      3-phenylpropionic acid (CPP). A single solvent extraction is then used to isolate
      the isotopomers of CPP along with the trans-cinnamic acid (TCA) produced from Phe
      by PAL, as well as the TCA metabolites benzoic and hippuric acids. This procedure
      eliminates the need for a separate ion-exchange isolation step for Phe on a
      second sample aliquot and separate GC-MS analysis. Extracted CPP and the Phe
      metabolites are then measured by conversion to the pentafluorobenzyl esters and a
      single analysis by electron capture negative ion GC-MS. The estimated lower limit
      of quantitation is 0.1 microM.

PMID- 17511015
TI  - Hollow-fiber liquid-phase microextraction prior to low-temperature electrothermal
      vaporization ICP-MS for trace element analysis in environmental and biological
      samples.
AB  - A new method of hollow-fiber liquid-phase microextraction (HF-LPME) prior to
      electrothermal vaporization (ETV) inductively coupled plasma mass spectrometry
      (ICP-MS) determination of trace Cu, Zn, Pd, Cd, Hg, Pb and Bi, based on gaseous
      compounds introduction into the plasma as their diethyldithiocarbmate (DDTC)
      chelates, was developed. The use of the reagent DDTC as chemical modifier could
      not only enhance the analytical signals, but also decrease the vaporization
      temperature. At a temperature of 1300 degrees C, trace Cu, Zn, Pd, Cd, Hg, Pb and
      Bi can be vaporized completely into the ICP. The factors affecting the formation
      of the chelates and their vaporization behaviors were investigated in detail, and
      the microextraction conditions were optimized. Under the optimized conditions,
      the detection limits of the proposed method were 12.4, 28.7, 7.9, 4.5, 3.3, 4.8
      and 1.6 pg ml(-1) for Cu, Zn, Pd, Cd, Hg, Pb and Bi, respectively. Enrichment
      factors of 305, 284, 24, 29, 20, 73 and 43 could be achieved within 15 min of
      extraction time, and the relative standard deviations (RSDs) for the seven
      determinations of 0.5 ng ml(-1) of target analytes were 8.8, 6.9, 7.1, 9.4, 10.2,
      6.1 and 10.8%, respectively. The newly developed method has been applied to the
      determination of trace Cu, Zn, Pd, Cd, Hg, Pb and Bi in environmental water and
      human serum samples, and the recoveries for the spiked samples were in the range
      of 88-116%. In order to validate this method, two certified reference materials,
      GBW08501 peach leaves and GBW(E)080040 seawater, were analyzed, and the
      determined values were in good agreement with the certified values.

PMID- 17511016
TI  - Improved protein identification efficiency by mass spectrometry using N-terminal
      chemical derivatization of peptides from Angiostrongylus costaricensis, a
      nematode with unknown genome.
AB  - Matrix-assisted laser desorption ionization (MALDI), Peptide Mass Fingerprinting
      (PMF) and MALDI-MS/MS ion search (using MASCOT) have become the preferred methods
      for high-throughput identification of proteins. Unfortunately, PMF can be
      ambiguous, mainly when the genome of the organism under investigation is unknown
      and the quality of spectra generated is poor and does not allow confident
      identification. The post-source decay (PSD) fragmentation of singly charged
      tryptic peptide ions generated by MALDI-TOF/TOF typically results in low
      fragmentation efficiency and/or complex spectra, including backbone fragmentation
      ions (series b and y), internal fragmentation etc. Interpreting these data either
      manually and/or using de novo sequencing software can frequently be a challenge.
      To overcome this limitation when studying the proteome of adult Angiostrongylus
      costaricensis, a nematode with unknown genome, we have used chemical N-terminal
      derivatization of the tryptic peptides with 4-sulfophenyl isothiocyanate (SPITC)
      prior to MALDI-TOF/TOF MS. This methodology has recently been reported to enhance
      the quality of MALDI-TOF/TOF-PSD data, allowing the obtainment of complete
      sequence of most of the peptides and thus facilitating de novo peptide
      sequencing. Our approach, consisting of SPITC derivatization along with manual
      spectra interpretation and Blast analysis, was able to positively identify 76% of
      analyzed samples, whereas MASCOT analysis of derivatized samples, MASCOT analysis
      of nonderivatized samples and PMF of nonderivatized samples yielded only 35, 41
      and 12% positive identifications, respectively. Moreover, de novo sequencing of
      SPITC modified peptides resulted in protein sequences not available in NCBInr
      database paving the way to the discovery of new protein molecules.

PMID- 17511017
TI  - Assessment and validation of the MS/MS fragmentation patterns of the macrolide
      immunosuppressant everolimus.
AB  - Everolimus (40-O-(2-hydroxyethyl)rapamycin, Certican) is a 31-membered macrolide
      lactone. In lymphocytes, it inhibits the mammalian target of rapamycin (mTOR) and
      is used as an immunosuppressant after organ transplantation. Due to its
      instability in pure organic solvents and insufficient HPLC separation, NMR
      spectroscopy analysis of its metabolite structures is nearly impossible.
      Therefore, structural identification based on tandem mass spectrometry (MS/MS)
      and MS(n) fragmentation patterns is critical. Here, we have systematically
      assessed the fragmentation pattern of everolimus during liquid chromatography
      (LC)-electrospray ionization (ESI)-MS/MS and validated the fragment structures by
      (1) comparison with structurally identified derivatives (sirolimus), (2) high
      resolution mass spectrometry, (3) elucidation of fragmentation pathways using ion
      trap mass spectrometry (up to MS(5)) and (4) H/D exchange. In comparison with the
      structurally related immunosuppressants tacrolimus and sirolimus, our study was
      complicated by the low ionization efficiency of everolimus. Detection of positive
      ions gave the best sensitivity, and everolimus and its fragments were mainly
      detected as sodium adducts. LC-ESI-MS/MS of everolimus in combination with
      collision-induced dissociation (CID) resulted in a complex fragmentation pattern
      and the structures of 53 fragments were identified. These detailed fragmentation
      pathways of everolimus provided the basis for structural elucidation of all
      everolimus metabolites generated in vivo und in vitro.

PMID- 17511018
TI  - Anomeric information obtained from a series of synthetic trisaccharides using
      energy resolved mass spectra.
AB  - The majority of structural investigations of oligosaccharides based on mass
      spectrometry use naturally occurring oligosaccharides, which do not allow
      extracting any common feature associated with anomeric structures and linkage
      positions. In order to address the issue to find such characteristics possibly
      contained in oligosaccharide structure, a synthetic combinatorial trisaccharide
      library was analyzed. The trisaccharides used in the analysis consisted of L
      fucose, D-galactose and D-glucose, in which individual glycosidic linkages
      existed in either alpha- or beta-anomers. The analysis of energy-resolved mass
      spectra (ERMS) and the scattered plot analysis of some parameters obtained from
      ERMS for a series of trisaccharides revealed that lower activation energy was
      required for the dissociation of alpha-glycosides of these sugars compared to
      those of the corresponding beta-anomers. It is suggested that this finding may be
      useful in structural analysis of natural oligosaccharides.

PMID- 17511019
TI  - Identification of dimeric anthocyanins and new oligomeric pigments in red wine by
      means of HPLC-DAD-ESI/MSn.
AB  - High-pressure liquid chromatography-diode array detector-electrospray
      ionisation/ion trap mass spectrometry (HPLC-DAD-ESI/MS(n)) analyses carried out
      in red wine fractions revealed the existence of dimeric anthocyanins (A-A(+)),
      previously detected in grape skin, and allowed the detection and identification,
      for the first time, of other derived oligomers. The structure of these compounds
      was characterised according to their MS(n)(n = 1-4) fragmentation patterns. The
      newly detected oligomers consisted of a flavanol, (epi)catechin or
      (epi)gallocatechin, linked through its C(4) position to the nucleophilic
      positions of the upper unit of a dimeric anthocyanin (F-A-A(+)). All the
      compounds contained malvidin as one of the anthocyanin subunits, whereas the
      other anthocyanin moiety could be either delphinidin, cyanidin, petunidin,
      peonidin or malvidin. With the fractionation method employed, the dimeric
      anthocyanins eluted in the same fractions as the monomeric anthocyanins. However,
      the new F-A-A(+) oligomers were found in the same fractions as F-A(+) dimers,
      which might indicate a structural similarity between both types of compounds.
      ESI/MS(n) analyses, coupled or not to HPLC, showed to be a useful and powerful
      tool for detecting and identifying these oligomers in wines, which usually elute
      from reversed-phase columns as humps and/or are overlapped by the peaks of other
      compounds. The detection of these oligomeric pigments in wine has provided more
      information about the complex pigments responsible for the elevation of the base
      line observed in the chromatograms of wines and has also revealed that oligomeric
      anthocyanins can take part in the reactions usually undergone by monomeric
      anthocyanins.

PMID- 17511020
TI  - A sensitive and selective liquid chromatography-tandem mass spectrometry method
      for the simultaneous quantification of actinomycin-D and vincristine in children
      with cancer.
AB  - We describe a selective and a highly sensitive assay for actinomycin-D (Act-D)
      and vincristine (VCR) in plasma employing high-performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) detection. The intraday precision (as
      defined by the coefficient of variation, CV) based on the standard deviation of
      replicates of quality control samples ranged from 4.9 to 7.5% and 6.5 to 11.3%
      with accuracy ranging from 90.7 to 98.1% and 91.2 to 103% for Act-D and VCR,
      respectively. The interday precision ranged from 7.2 to 10.0% and 11.3 to 13.0%
      and the accuracy ranged from 94.3 to 102% and 90.7 to 91.6% for Act-D and VCR,
      respectively. Stability studies showed that Act-D and VCR were stable both during
      the assay procedure and long-term storage. The lower limit of quantitation (LLOQ)
      for both Act-D and VCR was 0.05 ng/ml. The analytical method showed excellent
      sensitivity, precision, and accuracy. This method is robust and is being
      successfully employed in a pharmacokinetic study of these agents in children with
      cancer, and is expected to support several ongoing and future pediatric trials.

PMID- 17511021
TI  - Difference in practice effects depending on cerebral perfusion pattern in mild
      cognitive impairment.

PMID- 17511022
TI  - Comprehensive liquid chromatography-ion-spray tandem mass spectrometry method for
      the identification and quantification of eight hydroxylated brominated diphenyl
      ethers in environmental matrices.
AB  - We propose an instrumental method based on liquid chromatography coupled to
      negative ion-spray ionization (ISP(-)) tandem mass spectrometry (MS/MS), for the
      simultaneous analysis of eight hydroxylated brominated diphenyl ethers (OH-PBDEs)
      in four different environmental matrices (soil, fish, sludge and particulate
      matter). The reversed-phase chromatographic separation was performed on a 50 mm
      Xbridge C18 column, and the compounds were well resolved with a gradient
      consisting of a ternary mixture of 5 mMammonium acetate, methanol and
      acetonitrile. Detection was performed in the multiple reaction monitoring (MRM)
      mode using the [M - H](-) ion as base peak. The fragmentation pathways of the OH
      PBDEs varied according to the hydroxyl substitution in the benzene rings and
      produced characteristic MRM transitions needed for resolving isomeric compounds.
      The method is acceptable for quantification in the high picogram per gram dry
      weight (dw) level for all matrices analyzed. Repeatability and reproducibility
      tested at 75 pg microl(-1) were below 10% using internal standard quantification.
      The ISP (-) enhancement due to matrix effects was in the 76-132% range and the
      highest values corresponded to sludge samples. The use of the proposed method
      based on LC-ISP(-)-MS/MS opens a new way to directly determine OH-PBDEs without
      the need of derivatization.

PMID- 17511023
TI  - Mutations in the CYP51 gene correlated with changes in sensitivity to sterol 14
      alpha-demethylation inhibitors in field isolates of Mycosphaerella graminicola.
AB  - In France, as in many other European countries, Mycosphaerella graminicola
      (Fuckel) Schroter in Cohn (anamorph Septoria tritici), the causal agent of wheat
      leaf blotch, is controlled by foliar applications of fungicides. With the recent
      generalization of resistance to strobilurins (QoIs), reliable control is mainly
      dependent upon inhibitors of sterol 14 alpha-demethylation (DMIs). To date,
      strains with reduced sensitivity to DMIs are widespread, but disease control
      using members of this class of sterol biosynthesis inhibitors has not been
      compromised. In this study, sensitivity assays based on in vitro effects of
      fungicides towards germ-tube elongation allowed the characterization of seven DMI
      resistant phenotypes. In four of them, cross-resistance was not observed between
      all tested DMIs; this characteristic concerned prochloraz, triflumizole,
      fluquinconazole and tebuconazole. Moreover, the highest resistant factors to most
      DMIs were found only in recent isolates; according to their response towards
      prochloraz, they were classified into two categories. Molecular studies showed
      that DMI resistance was associated with mutations in the CYP51 gene encoding the
      sterol 14 alpha-demethylase. Alterations at codons 459, 460 and 461 were related
      to low resistance levels, whereas, at position 381, a valine instead of an
      isoleucine, in combination with the previous changes, determined the highest
      resistance levels to all DMIs except prochloraz. Mutations in codons 316 and 317
      were also found in some isolates exhibiting low resistance factors towards most
      DMIs.

PMID- 17511025
TI  - Cyclooxygenase-2 expression after preoperative chemoradiotherapy correlates with
      more frequent esophageal cancer recurrence.
AB  - AIM: To investigate the relationship between cycloo-xygenase-2 (COX-2), and
      vascular endothelial growth factor (VEGF), and to determine the clinical
      significance of this relationship in esophageal cancer patients undergoing
      chemoradiotherapy (CRT). METHODS: Immunohistochemical staining was used to
      evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed
      esophageal squamous carcinoma (ESCC) who were undergoing preoperative CRT.
      RESULTS: Fourteen out of 40 ESCC patients showed a pathological complete response
      (CR) after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm
      of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors,
      respectively. COX-2 expression was strongly correlated with VEGF expression
      (P<0.05). There were also significant associations between COX-2 expression,
      tumor recurrence, and lymph-node involvement (P=0.0277 and P=0.0095,
      respectively). COX-2 expression and VEGF expression had significant prognostic
      value for disease-free survival (log-rank test; P=0.0073 and P=0.0341,
      respectively), but not for overall survival, as assessed by univariate analysis.
      CONCLUSION: Our results suggest that COX-2 expression correlates with VEGF
      expression and might be a useful prognostic factor for more frequent tumor
      recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support
      the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.

PMID- 17511026
TI  - Effect of herbal medicine Juzentaihoto on hepatic and intestinal heat shock gene
      expression requires intestinal microflora in mouse.
AB  - AIM: To evaluate the role of intestinal microflora in the effects of multi-herbal
      medicine on gene expression in the gut and liver. METHODS: The multi-herbal
      medicine Juzentaihoto (JTX) was administered to five germ-free mice and regular
      mice for 2 wk. Among the results of the comprehensive gene chip analysis of the
      intestine and liver, we featured heat shock proteins (HSPs) 70 and 105 because
      their gene expression changed only in the presence of microflora. Real-time RT
      PCR was performed to confirm the expression levels of these HSP genes. To
      determine whether JTX acts directly on the HSP genes, sodium arsenite (SA) was
      used to induce the heat shock proteins directly. To examine the change of the
      intestinal microflora with administration of JTX, the terminal restriction
      fragment polymorphism (T-RFLP) method was used. To identify the changed bacteria,
      DNA sequencing was performed. RESULTS: Heat shock protein gene expression,
      documented by gene chip and real-time RT-PCR, changed with the administration of
      JTX in the regular mice but not in the germ-free mice. JTX did not suppress the
      direct induction of the HSPs by SA. T-RFLP suggested that JTX decreased
      unculturable bacteria and increased Lactobacillus johnsoni. These data suggested
      that JTX changed the intestinal microflora which, in turn, changed HSP gene
      expression. CONCLUSION: Intestinal microflora affects multi-herbal product JTX on
      the gene expression in the gut and liver.

PMID- 17511024
TI  - Genetics of hepatocellular carcinoma.
AB  - The completely assembled human genome has made it possible for modern medicine to
      step into an era rich in genetic information and high-throughput genomic
      analysis. These novel and readily available genetic resources and analytical
      tools may be the key to unravel the molecular basis of hepatocellular carcinoma
      (HCC). Moreover, since an efficient treatment for this disease is lacking,
      further understanding of the genetic background of HCC will be crucial in order
      to develop new therapies aimed at selected targets. We report on the current
      status and recent developments in HCC genetics. Special emphasis is given to the
      genetics and regulation of major signalling pathways involved in HCC such as p53,
      Wnt-signalling, TGFbeta, Ras, and Rb pathways. Furthermore, we describe the
      influence of chromosomal aberrations as well as of DNA methylation. Finally, we
      report on the rapidly developing field of genomic expression profiling in HCC,
      mainly by microarray analysis.

PMID- 17511027
TI  - Selective cyclooxygenase-2 inhibitor ameliorates cholecystokinin-octapeptide
      induced acute pancreatitis in rats.
AB  - AIM: To investigate the effect of selective Cycloo-xygenase-2 (COX-2) inhibitor 4
      [5-(4-Chloro-phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC
      236), on the cholecystokinin (CCK)-octapeptide-induced acute pancreatitis (AP) in
      rats. METHODS: Wistar rat weighing 240 g to 260 g were divided into three groups.
      (1) Normal DMSO treated group, (2) SC-236 at 4 mg/kg treated group; SC-236
      systemically administered via the intravenous (i.v.) catheter, followed by 75
      microg/kg CCK octapeptide subcutaneously three times, after 1, 3 and 5 h. This
      whole procedure was repeated for 5 d. (3) Dimethyl sulfoxide (DMSO) treated
      group: an identical protocol was used in this group as in the SC-236 cohort (see
      2. above). Repeated CCK octapeptide treatment resulted in a typical
      experimentally induced pancreatitis in the Wistar rats. RESULTS: SC-236 improved
      the severity of CCK-octapeptide-induced AP as measured by laboratory criteria
      [the pancreatic weight/body weight (p.w/b.w) ratio, the level of serum amylase
      and lipase]. The SC-236 treated group showed minimal histologic evidence of
      pancreatitis and a significant reduction in myeloperoxidase activity. SC-236 also
      increased heat shock protein (HSP)-60 and HSP72 compared with the DMSO-treated
      group in the CCK-octapeptide-induced AP and also reduced the pancreatic levels of
      COX-2. Furthermore, SC-236 reduced proinflammatory cytokine synthesis and
      inhibited NF-kappaB activation compared with the DMSO-treated group in the CCK
      octapeptide-induced AP. CONCLUSION: Our results suggested that COX-2 plays
      pivotal role in the development of AP and COX-2 inhibitors may play a beneficial
      role in preventing AP.

PMID- 17511028
TI  - Expression of SNC73, a transcript of the immunoglobulin alpha-1 gene, in human
      epithelial carcinomas.
AB  - AIM: To investigate the expression of SNC73, a trans-cript of the immunoglobulin
      alpha-1 gene (IgA1-H chain), in human epithelia-derived tumor cells. METHODS:
      Total RNAs and cell lysates were prepared from five different human epithelial
      cell lines derived from lung, stomach, liver, skin, and breast, respectively. RT
      PCR and immunoblot analysis of these five cell lines were done. Both RT-PCR and
      immunochemistry were used to detect the expression of SNC73 in these cell lines.
      We also examined the expression of SNC73 in normal epithelial cells of colon
      mucosa by in situ hybridization. RT-PCR and immunoblot analysis were used to
      determine whether the recombination activating gene1/2 (RAG1 and RAG2) is
      present. The expression of three immunoglobulin transcription factors, EBF, E2A
      and Pax5, and the heavy chain of IgA1 and two types of light chains of
      immunoglobulin (kappa and lambda) in the aforementioned cell lines were analyzed
      by RT-PCR and immunochemistry, respectively. All the RT-PCR products were
      analyzed by sequencing. RESULTS: The results of RT-PCR and immunochemistry showed
      that both mRNA and protein of SNC73 were expressed in five human epithelia
      derived cancer cell lines. These data were further confirmed in the normal
      epithelial cells of colon mucosa by in situ hybridization. Also, the heavy chain
      of IgA1 and kappa light chain were detected in these cells, but no lambda light
      chain was obse-rved. Both RAG1 and RAG2 were expressed in these human epithelia
      derived cancer cell lines and the sequence was identical to that expressed in pre
      B and pre-T cells. In addition to RAG1 and RAG2, the mRNA in one of the
      immunoglobulin transcription factors, EBF, was also detected in these cell lines,
      and Pax5 was only expressed in SW480 cells, but no expression of E2A was observed
      in all the five cell lines. CONCLUSION: Immunoglobulin A1 is originally expressed
      and V(D)J recombination machine is also present in non-lymphoid cells, suggesting
      that V(D)J recombination machine mediates the assembly of immunoglobulin A1 in
      non-lymphoid cells as in pre-lymphocytes.

PMID- 17511029
TI  - Update on Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti
      neutrophil antibodies and antibodies to exocrine pancreas detected by indirect
      immunofluorescence as biomarkers in chronic inflammatory bowel diseases: results
      of a multicenter study.
AB  - AIM: Anti-Saccharomyces cerevisiae antibodies (ASCA), anti-nuclear associated
      anti-neutrophil antibodies (NANA) and antibodies to exocrine pancreas (PAB), are
      serological tools for discriminating Crohn's disease (CrD) and ulcerative colitis
      (UC). Like CrD, coeliac disease (CoD) is an inflammatory bowel disease (IBD)
      associated with (auto) antibodies. Performing a multicenter study we primarily
      aimed to determine the performance of ASCA, NANA and PAB tests for IBD diagnosis
      in children and adults, and secondarily to evaluate the prevalence of these
      markers in CoD. METHODS: Sera of 109 patients with CrD, 78 with UC, 45 with CoD
      and 50 healthy blood donors were retrospectively included. ASCA, NANA and PAB
      were detected by indirect immunofluorescence (IIF). RESULTS: ASCA+/NANA- profile
      displayed a positive predictive value of 94.2% for CrD. Detection of ASCA was
      correlated with a more severe clinical profile of CrD and treatment of the
      disease did not influence their serum levels. ASCA positivity was found in 37.9%
      of active CoD. PAB were found in 36.7% CrD and 13.3% CoD patients and were not
      correlated with clinical features of CrD, except with an early onset of the
      disease. Fifteen CrD patients were ASCA negative and PAB positive. CONCLUSION:
      ASCA and PAB detected by IIF are specific markers for CrD although their presence
      does not rule out a possible active CoD. The combination of ASCA, NANA and PAB
      tests improves the sensitivity of immunological markers for CrD. Repeating ASCA,
      NANA, and PAB testing during the course of CrD has no clinical value.

PMID- 17511030
TI  - Characterization of hepatic progenitors from human fetal liver using CD34 as a
      hepatic progenitor marker.
AB  - AIM: To enrich putative hepatic progenitors from the developing human fetal liver
      using CD34 as a marker. METHODS: Aborted fetuses of 13-20 wk were used for the
      isolation of liver cells. The cells were labeled with anti CD34; a marker used
      for isolating progenitor population and the cells were sorted using magnetic cell
      sorting. The positive fractions of cells were assessed for specific hepatic
      markers. Further, these cells were cultured in vitro for long term investigation.
      RESULTS: Flow cytometric and immunocytochemical analysis for alphafetoprotein
      (AFP) showed that the majority of the enriched CD34 positive cells were positive
      for AFP. Furthermore, these enriched cells proliferated in the long term and
      maintained hepatic characteristics in in vitro culture. CONCLUSION: The study
      shows that aborted human fetal liver is a potential source for isolation of
      hepatic progenitors for clinical applications. The study also demonstrates that
      CD34 can be a good marker for the enrichment of progenitor populations.

PMID- 17511031
TI  - Combination of small interfering RNA and lamivudine on inhibition of human B
      virus replication in HepG2.2.15 cells.
AB  - AIM: To observe the inhibition of hepatitis B virus (HBV) replication and
      expression by combination of siRNA and lamivudine in HepG2.2.15 cells. METHODS:
      Recombinant plasmid psil-HBV was constructed and transfected into HepG2.2.15
      cells. The transfected cells were cultured in lamivudine-containing medium (0.05
      micromol/L) and harvested at 48, 72 and 96 h. The concentration of HBeAg and
      HBsAg was determined using ELISA. HBV DNA replication was examined by real-time
      PCR and the level of HBV mRNA was measured by RT-PCR. RESULTS: In HepG2.2.15
      cells treated with combination of siRNA and lamivudine, the secretion of HBeAg
      and HBsAg into the supernatant was found to be inhibited by 91.80% and 82.40%
      (2.89+/-0.48 vs 11.73+/-0.38, P<0.05; 4.59+/-0.57 vs 16.25+/-0.48, P<0.05) at 96
      h, respectively; the number of HBV DNA copies within culture medium was also
      significantly decreased at 96 h (1.04+/-0.26 vs 8.35+/-0.33, P<0.05). Moreover,
      mRNA concentration in HepG2.2.15 cells treated with combination of siRNA and
      lamivudine was obviously lower compared to those treated either with siRNA or
      lamivudine (19.44+/-0.17 vs 33.27+/-0.21 or 79.9+/-0.13, P<0.05). CONCLUSION:
      Combination of siRNA and lamivudine is more effective in inhibiting HBV
      replication as compared to the single use of siRNA or lamivudine in HepG2.2.15
      cells.

PMID- 17511032
TI  - Adalimumab induction therapy for ulcerative colitis with intolerance or lost
      response to infliximab: an open-label study.
AB  - AIM: To evaluate the efficacy of adalimumab induction therapy in patients with
      ulcerative colitis who previously responded to infliximab and then lost response
      or became intolerant. METHODS: Ten patients with ulcerative colitis were enrolled
      in a 4-wk open-label trial. The patients received a loading dose of 160 mg
      adalimumab at wk 0 followed by 80 mg at wk 2. The primary efficacy measure was
      clinical improvement at wk 4, as defined by a decrease in clinical activity index
      (CAI) of more than 4. RESULTS: Four of 10 patients (40%) benefited from
      subsequent adalimumab therapy; one patient achieved remission (CAI<4) and 3 had
      clinical improvement at wk 4. 6 patients had no response (60%); 2 of 6 (33.3%)
      subsequently underwent colectomy. This was accompanied by a decrease in median
      CRP concentration from 16.8 mg/mL at baseline to 3.85 mg/mL at wk 4, excluding
      two patients who underwent colectomy after two infusions of adalimumab. Among the
      6 patients with severe colitis (CAI>12) at baseline, none achieved remission and
      only one patient had clinical improvement at wk 4. CONCLUSION: The small
      advantage of adalimumab in patients with mild to moderate ulcerative colitis and
      lost response or intolerance to infliximab needs to be confirmed in randomised,
      double-blind, placebo-controlled trials.

PMID- 17511033
TI  - Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia.
AB  - AIM: To quantify the intraepithelial lymphocytes (IELs) and to document the
      membrane expression of CD4, CD8, TCRgamma delta and adhesion and/or activation
      associated molecules (CD103, CD28, CD44, CD69, HLA-DR, CD95/Fas) in the duodenal
      mucosa of patients with functional dyspepsia (FD) in order to provide arguments
      for an immunological process in FD. METHODS: Twenty-six FD patients according to
      Rome II criteria (20 were H pylori negative) were studied and compared to 12
      healthy adults. IELs were isolated from five duodenal biopsy samples, then
      quantified by microscopy and flow cytometry while the membrane phenotypes were
      determined by cytofluorometry. RESULTS: Duodenal histological examination was
      normal. In H pylori negative patients, the number of IELs was not different from
      that in healthy controls. Median percentage expression of CD4, CD8, or TCRgamma
      delta and CD103, CD44, CD28, CD69 on CD3+ IELs, among the adhesion/activation
      associated molecules tested, was not different from that in healthy controls. In
      contrast, the median percentage expression of CD95/Fas [22 (9-65) vs 45 (19-88),
      P=0.03] and HLA-DR expressing CD3+ IELs [4 (0-30) vs 13 (4-42), P=0.04] was
      significantly lower in the H pylori negative FD group than in healthy controls,
      respectively. The number of IELs was significantly greater in H pylori positive
      FD patients than in healthy controls [median ratio for 100 enterocytes 27.5 (6.7
      62.5) vs 10.8 (3-33.3), P=0.02] due to a higher number of CD8+ CD3+ IELs.
      CONCLUSION: In H pylori negative FD patients, the phenotypic characterization of
      IELs suggests that we cannot exclude a role of IELs in FD.

PMID- 17511034
TI  - Sphincter-preserving R0 total mesorectal excision with resection of internal
      genitalia combined with pre- or postoperative chemoradiation for T4 rectal cancer
      in females.
AB  - AIM: To evaluate the impact of chemoradiation admi-nistered pre- or
      postoperatively on prognosis in females following R0 extended resection with
      sphincter-preserving total mesorectal excision (TME) for locally advanced rectal
      cancer and to assess the association between chemoradiation and intra- and
      postoperative variables. METHODS: Twenty-one females were treated for locally
      advanced but preoperatively assessed as primarily resectable rectal cancer
      involving reproductive organs. Anterior resection with TME and excision of
      internal genitalia was combined with neo- or adjuvant chemoradiation. Two-year
      disease-free survival analysis was performed with the Kaplan-Meier method and log
      rank test. The association between chemoradiation and other variables was
      evaluated with the Fisher's exact test and Mann-Whitney test. RESULTS: Survival
      rate decreased in anaemic females (51.5% vs 57.4%), in patients older than 60
      years (41.8% vs 66.7%) with poorly differentiated cancers (50.0% vs 55.6%) and
      tumors located<or=7 cm from the anal verge (42.9% vs 68.1%) but with the lack of
      importance. Patients with negative lymph nodes and women chemoradiated
      preoperatively had significantly favourable prognosis (85.7% vs 35.7%; P=0.03 and
      80.0% vs 27.3%; P=0.01, respectively). Preoperative chemoradiation compared to
      adjuvant radiochemotherapy was not significantly associated with the duration of
      surgery, incidence of intraoperative bowel perforation and blood loss>or=1 L,
      rate of postoperative bladder and anorectal dysfunction, and minimal distal
      resection margin. It significantly influenced minimal radial margin (mean 4.2 mm
      vs 1.1 mm; P<0.01). CONCLUSION: Despite involving internal genitalia, long-term
      disease-free survival and sphincter preservation may be achieved with combined
      modality therapy for females with T4 locally advanced rectal carcinoma.
      Neoadjuvant chemoradiation does not compromise functional results and may
      significantly improve oncological outcomes probably due to enhanced radial
      clearance.

PMID- 17511035
TI  - Type I inositol 1, 4, 5-triphosphate receptors increase in kidney of mice with
      fulminant hepatic failure.
AB  - AIM: To delineate the mechanisms of renal vasocon-striction in hepatorenal
      syndrome (HRS), we investigated the expression of type I inositol 1, 4, 5
      triphosphate receptors (IP3RI) of kidney in mice with fulminant hepatic failure
      (FHF). METHODS: FHF was induced by lipopolysaccharide (LPS) in D-galactosamine
      (GalN) sensitized BALB/c mice. There were 20 mice in normal saline (NS)-treated
      group, 20 mice in LPS-treated group, 20 mice in GalN-treated group, and 60 mice
      in GalN/LPS-treated group (FHF group). Liver and kidney tissues were obtained at
      2, 6, and 9 h after administration. The liver and kidney specimens were stained
      with hematoxylin-eosin for studying morphological changes under light microscope.
      The expression of IP3RI in kidney tissue was tested by immunohistochemistry,
      Western blot and reverse transcription (RT)-PCR. RESULTS: Kidney tissues were
      morphologically normal at all time points in all groups. IP3RI proteins were
      found localized in the plasma region of glomerular mesangial cells (GMC) and
      vascular smooth muscle cells (VSMC) in kidney by immunohistochemical staining. In
      kidney of mice with FHF at 6 h and 9 h IP3RI staining was up-regulated. Results
      from Western blot demonstrated consistent and significant increment of IP3RI
      expression in mice with FHF at 6 h and 9 h (t=3.16, P<0.05; t=5.43, P<0.01).
      Furthermore, we evaluated IP3RI mRNA expression by RT-PCR and observed marked up
      regulation of IP3RI mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls
      (t=2.97, P<0.05; t=4.42, P<0.01; t=3.81, P<0.01). CONCLUSION: The expression of
      IP3RI protein increased in GMC and renal VSMC of mice with FHF, possibly caused
      by up-regulation of IP3RI mRNA.

PMID- 17511036
TI  - H pylori seroprevalence in patients with lung cancer.
AB  - AIM: To assess H pylori seroprevalence in lung cancer and determine whether there
      is a potential association between lung cancer and H pylori infection. METHODS:
      The study was conducted on forty consecutive patients with lung cancer, confirmed
      by pathology (32 men, 8 women; mean age 55.50+/-11.91 years, range 16-77 years).
      Forty healthy subjects (25 men, 15 women; mean age 43.08+/-12.60 years, range 20
      79 years) from the patients' family members were matched to each case subject on
      the basis of age and socioeconomic status. H pylori infection was detected with a
      commercially available immunoglobulin G (IgG) enzyme-linked immunosorbent assay
      (Trinity kit, Biotech co., USA), previously validated in adults (86% sensitivity,
      96% specificity) against a gold standard of culture and histology. RESULTS: H
      pylori seropositivity was present in 52.5% of patients with lung cancer in
      comparison to 45.0% of healthy control subjects. Although H pylori seropositivity
      was more frequent in lung cancer patients than in controls, the difference did
      not reach statistical significance (OR=1.35, 95% CI=0.56-3.25; P=0.65). In
      addition, there was no significant difference between cases and controls in terms
      of gastrointestinal symptoms. CONCLUSION: The earlier described association
      between H pylori infection and lung cancer was not supported in this study.
      Further studies with larger sample sizes should be undertaken to assess the
      frequency of H pylori infection in patients with lung cancer and their potential
      association.

PMID- 17511037
TI  - Ethanol induced mitochondria injury and permeability transition pore opening:
      role of mitochondria in alcoholic liver disease.
AB  - AIM: To observe changes of mitochondria and investigate the effect of ethanol on
      mitochondrial perme-ability transition pore (PTP), mitochondrial membrane
      potential (MMP, Delta psi m) and intracellular calcium concentration in
      hepatocytes by establishing an animal model of alcoholic liver disease (ALD).
      METHODS: Fourty adult male Wistar rats were randomly divided into two groups, the
      model group (20) was administered alcohol intragastrically plus an Oliver oil
      diet to establish an ALD model, and the control group (20) was given an equal
      amount of normal saline. The ultramicrostructural changes of mitochondria were
      observed under electron microscopy. Mitochondria of liver was extracted, and
      patency of PTP, mitochondrial membrane potential (Delta psi m), mitochondrial
      mass and intracellular calcium concentration of isolated hepacytes were detected
      by flow cytometry using rhodamine123 (Rh123), Nonyl-Acridine Orange and calcium
      fluorescent probe Fluo-3/AM, respectively. RESULTS: Membrane and cristae were
      broken or disappeared in mitochondria in different shapes under electron
      microscopy. Some mitochondria showed U shape or megamitochondrion. In the model
      group, liver mitochondria PTP was broken, and mitochondria swelled, the
      absorbance at 450 nm, A540 decreased (0.0136+/-0.0025 vs 0.0321+/-0.0013, model
      vs control, P<0.01); mitochondria transmembrane potential (239.4638+/-12.7263 vs
      377.5850+/-16.8119, P<0.01) was lowered; mitochondrial mass (17.4350+/-1.9880 vs
      31.6738+/-3.4930, P<0.01); and [Ca2+]i was increased in liver cells (7.0020+/
      0.5008 vs 10.2050+/-0.4701, P<0.01). CONCLUSION: Chronic alcohol intake might
      lead to broken mitochondria PTP, decreased mitochondria membrane potential and
      injury, and elevated intracellular Ca2+ production. Ethanol-induced chondriosome
      injury may be an important mechanism of alcoholic diseases.

PMID- 17511038
TI  - Study on the blood-borne virus co-infection and T lymphocyte subset among
      intravenous drug users.
AB  - AIM: To investigate the features of various blood-borne virus infections and co
      infection in intravenous drug users (IDUs), and to examine the correlation of T
      lymphocyte subsets with virus co-infection. METHODS: Four hundred and six IDUs
      without any clinical manifestation of hepatitis and 102 healthy persons were
      enrolled in this study. HBV-DNA and HCV-RNA were detected by fluorescence
      quantitative PCR. HBsAg, HBeAg, anti-HBc, anti-HCV, HDV-Ag, anti-HGV, anti-HIV,
      and HCMV-IgM were assayed by enzyme-linked immunosorbent assay (ELISA) and
      immunochromatographic tests. The levels of Th1 and Th2 cytokines were measured by
      ELISA and radioactive immune assay (RIA). The T lymphocyte subpopulation was
      detected by using fluorescence immunoassay. The similar indices taken from the
      healthy persons served as controls. RESULTS: The viral infection rate among IDUs
      was 36.45% for HBV, 69.7% for HCV, 47.3% for HIV, 2.22% for HDV, 1.97% for HGV,
      and 3.45% for HCMV. The co-infection rate of blood-borne virus was detected in
      255 of 406 (62.81%) IDUs. More than 80% (161/192) of subjects infected with HIV
      were co-infected with the other viruses, such as HBV, HCV. In contrast, among the
      controls, the infection rate was 17.65% for HBV and 0% for the other viruses. Our
      investigation showed that there was a profound decrease in the proportion of
      CD4/CD8 and the percentage of CD3 and CD4, but not in the percentage of CD8. The
      levels of PHA-induced cytokines (IFN-gamma and IL-4) and serum IL-2 were
      obviously decreased in IDUs. On the other hand, the level of serum IL-4 was
      increased. The level of IFN-gamma and the percentage of CD4 were continuously
      decreased when the IDUs were infected with HIV or HIV co-infection. IDUs with HIV
      and HBV co-infection was 15.1% (29/192). Of those 29 IDU with HIV and HBV co
      infection, 51.72% (15/29) and 37.93% (11/29) were HBV-DNA-positive and HBeAg
      positive, respectively. But, among IDUs without HIV infection, only 1.68% (2/119)
      of cases were HBV-DNA-positive. CONCLUSION: HCV, HBV and HIV infections are
      common in this population of IDU, leading to a high incidence of impaired Th1
      cytokine levels and CD4 lymphocyte. IDUs with HIV and HBV/HCV co-infection have
      lower expression of Th1 cytokine with enhancement of the Th2 response. HIV may be
      causing HBV replication by decreasing Th1 function.

PMID- 17511039
TI  - Selenoprotein P mRNA expression in human hepatic tissues.
AB  - AIM: To investigate the expression of selenoprotein P mRNA (SePmRNA) in tissues
      of normal liver, liver cirrhosis and hepatocellular carcinoma (HCC), and its
      relationship with HCC occurrence and development. METHODS: The expression of
      SePmRNA in tissues of normal liver, liver cirrhosis and HCC were detected by in
      situ hybridization using a cDNA probe. RESULTS: The enzyme digesting products of
      PBluescript-Human Selenoprotein P were evaluated by electrophoresis. The positive
      expression of SePmRNA was found in the tissues of normal liver, liver cirrhosis
      and HCC. The expression of SeP mRNA was found in hepatic interstitial substance,
      especially in endothelial cells and lymphocytes of vasculature. The positive rate
      of SePmRNA in normal liver tissue was 84.6% (11/13) and the positive signals
      appeared in the nucleus and cytoplasm, mostly in the nucleolus, and the staining
      granules were larger in the nucleolus and around the nucleus. The positive rate
      of SePmRNA in liver cirrhosis tissue was 45.0% (9/20) and the positive signals
      were mainly in the nucleolus and cytoplasm, being less around the nucleus and
      inner nucleus than that in normal liver tissue. The positive rate of SePmRNA in
      HCC tissue was 30.0% (9/30) and the positive signals were in the cytoplasm, but
      less in the nucleus. CONCLUSION: SePmRNA expression in the tissues of normal
      liver and HCC is significantly different (84.6% vs 30.0%, P=0.003), suggesting
      that SeP might play a role in the occurrence and development of HCC.

PMID- 17511040
TI  - Hypoxia inducible factor-1alpha mediates protective effects of ischemic
      preconditioning on ECV-304 endothelial cells.
AB  - AIM: To investigate whether hypoxia inducible factor-1alpha (HIF-1alpha) is
      linked to the protective effects of ischemic preconditioning (IP) on sinusoidal
      endothelial cells against ischemia/reperfusion injury. METHODS: Sinusoidal
      endothelial cell lines ECV-304 were cultured and divided into four groups:
      control group, cells were cultured in complete DMEM medium; cold anoxia/warm
      reoxygenation (A/R) group, cells were preserved in a 4 centigrade UW solution in
      a mixture of 95% N2 and 5% CO2 for 24 h; anoxia-preconditioning (APC) group,
      cells were treated with 4 cycles of short anoxia and reoxygenation before
      prolonged anoxia-preconditioning treatment; and anoxia-preconditioning and
      hypoxia inducible factor-1alpha (HIF-1alpha) inhibitor (I-HIF-1) group, cells
      were pretreated with 5 microm of HIF-1alpha inhibitor NS398 in DMEM medium before
      subjected to the same treatment as group APC. After the anoxia treatment, each
      group was reoxygenated in a mixture of 95% air and 5% CO2 incubator for 6 h.
      Cytoprotections were evaluated by cell viabilities from Trypan blue, lactate
      dehydrogenase (LDH) release rates, and intracellular cell adhesion molecule-1
      (ICAM-1) expressions. Expressions of HIF-1alpha mRNA and HIF-1alpha protein from
      each group were determined by the RT-PCR method and Western blotting,
      respectively. RESULTS: Ischemia preconditioning increased cell viability, and
      reduced LDH release and ICAM-1 expressions. Ischemia preconditioning also
      upregulated the HIF-1alpha mRNA level and HIF-1alpha protein expression. However,
      all of these changes were reversed by HIF-1alpha inhibitor NS398. CONCLUSION:
      Ischemia preconditioning effectively inhibited cold hypoxia/warm reoxygenation
      injury to endothelial cells, and the authors showed for the first time HIF-1alpha
      is causally linked to the protective effects of ischemic preconditioning on
      endothelial cells.

PMID- 17511041
TI  - Bile duct injuries associated with laparoscopic and open cholecystectomy: sixteen
      year experience.
AB  - AIM: To summarize the experience in diagnosis, management and prevention of
      iatrogenic bile duct injury (IBDI). METHODS: A total of 210 patients with bile
      duct injury occurred during cholecystectomy admitted to Hunan Provincial People's
      Hospital from March 1990 to March 2006 were included in this study for
      retrospective analysis. RESULTS: There were 59.5% (103/173) of patients with IBDI
      resulting from the wrong identification of the anatomy of the Calot's triangle
      during cholecystectomy. The diagnosis of IBDI was made on the basis of clinical
      features, diagnostic abdominocentesis and imaging findings. Abdominal B
      ultrasonography (BUS) was the most popular way for IBDI with a diagnostic rate of
      84.6% (126/149). Magnetic resonance cholangiography (MRC) could reveal the site
      of injury, the length of injured bile duct and variation of bile duct tree with a
      diagnostic rate 100% (45/45). According to the site of injury, IBDI could be
      divided into six types. The most common type (type 3) occurred in 76.7% (161/210)
      of the patients and was treated with partial resection of the common hepatic duct
      and common bile duct. One hundred and seventy-six patients were followed up. The
      mean follow-up time was 3.7 (range 0.25-10) years. Good results were achieved in
      87.5% (154/176) of the patients. CONCLUSION: The key to prevention of IBDI is to
      follow the "identifying-cutting-identifying" principle during cholecystectomy. Re
      operation time and surgical procedure are decided according to the type of IBDI.

PMID- 17511042
TI  - An extremely rare case of delusional parasitosis in a chronic hepatitis C patient
      during pegylated interferon alpha-2b and ribavirin treatment.
AB  - During treatment of chronic hepatitis C patients with interferon and ribavirin, a
      lot of side effects are described. Twenty-three percent to 44% of patients
      develop depression. A minority of patients evolve to psychosis. To the best of
      our knowledge, no cases of psychogenic parasitosis occurring during interferon
      therapy have been described in the literature. We present a 49-year-old woman who
      developed a delusional parasitosis during treatment with pegylated interferon
      alpha-2b weekly and ribavirin. She complained of seeing parasites and the larvae
      of fleas in her stools. This could not be confirmed by any technical examination.
      All the complaints disappeared after stopping pegylated interferon alpha-2b and
      reappeared after restarting it. She had a complete sustained viral response.

PMID- 17511043
TI  - Appendiceal mucocoeles and pseudomyxoma peritonei.
AB  - Mucocoele of the appendix occurs when obstruction of the appendiceal lumen
      results in mucus accumulation and consequent abnormal dilatation. The most
      important aetiology, from a surgical perspective, is either mucinous cystadenoma
      or cystadenocarcinoma. In the latter, a spontaneous or iatrogenic rupture of the
      mucocoele can lead to mucinous intraperitoneal ascites, a syndrome known as
      pseudomyxoma peritonei. Optimal management of mucoceles is achieved through
      accurate preoperative identification and subsequent careful resection. We report
      two cases and subsequently discuss the clinical presentation of mucocoeles, their
      association with pseudomyxoma peritonei and an optimal management of both
      conditions.

PMID- 17511044
TI  - Gastrointestinal stromal tumor of the stomach with a giant abscess penetrating
      the gastric lumen.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. In large GISTs, cystic degeneration, necrosis and
      focal hemorrhage that occur inside the tumor can result in gastrointestinal
      bleeding. We describe a case of a 74-year old male with GIST of the stomach
      accompanied with a giant abscess that penetrated the gastric lumen. The patient
      experienced undiagnosed fever for two months prior to hospitalization.
      Gastrointestinal endoscopy, X-ray series and computed tomography of the patient's
      abdomen revealed a gastric submucosal tumor in the fornix, with a fistula to the
      gastric lumen that was inundated with a great deal of pus. The mass was diagnosed
      as a GIST from biopsy specimens. The patient was treated by endoscopic drainage
      of the abscess and intravenous administration of antibiotics. Eventually, a
      partial gastrectomy was performed. He was also administered Imanitib mesylate as
      adjuvant therapy. He was followed up for 2 years and no metastasis or recurrence
      was recognized at the follow-up examinations. This is the first report of a
      patient with clearly diagnosed GIST with endoscopic evidence of an abscess
      penetrating into the gastric lumen.

PMID- 17511045
TI  - Giant hepatic hydatid cyst: a case report.
AB  - Large type 1 cysts are prone to perforation. Furthermore, insufficient drainage
      with subsequent abscess is a frequent problem of large cysts. We report here a
      case of a 19-year old man who was admitted to the hospital with pain in the right
      upper quadrant and epigastric region. An asymmetrical right upper quadrant
      enlargement was detected on physical examination. Ultrasonography and
      computerized tomography revealed a type 1 giant hydatid cyst in the right hepatic
      lobe, measuring 16 cm in diameter. During operation, partial cystectomy and
      drainage were done. The large dead space was obliterated by the 'sandwich'
      method. Omentum and gelatin sponges were used to fill the cavity. The
      postoperative period was uneventful and the patient was discharged on the 5th
      postoperative day.

PMID- 17511046
TI  - Inactivation of digestive proteases: another aspect of gut bacteria that should
      be taken into more consideration.

PMID- 17511047
TI  - Trichinellosis in human and animals--new challenge. Proceedings of a conference,
      Warsaw, Poland,2006.

PMID- 17511048
TI  - Proceedings of the International Symposium for the Evaluation of Butadiene and
      Chloroprene Health Risks, September 20-22, 2005, Charleston, South Carolina, USA.

PMID- 17511050
TI  - Potential impact of AUSFTA on Australia's blood supply. Comment.

PMID- 17511049
TI  - Atrial Fibrillation: State of the Art. Proceedings of a symposium, October 27-29,
      2006, Marina del Rey, California, USA.

PMID- 17511051
TI  - Proceedings and abstracts of the Annual Conference of the International Embryo
      Transfer Society, Kyoto, Japan, 6-10 January 2007.

PMID- 17511052
TI  - In memory of Ilse Hagedorn.

PMID- 17511053
TI  - Abstracts of the 66th Scientific Sessions of the American Diabetes Association,
      June 9-13, 2006, Washington, DC, USA.

PMID- 17511054
TI  - Endoscopic versus surgical treatment for chronic pancreatitis.

PMID- 17511055
TI  - Endoscopic versus surgical treatment for chronic pancreatitis.

PMID- 17511056
TI  - Endoscopic versus surgical treatment for chronic pancreatitis.

PMID- 17511057
TI  - Endoscopic versus surgical treatment for chronic pancreatitis.

PMID- 17511058
TI  - Endoscopic versus surgical treatment for chronic pancreatitis.

PMID- 17511059
TI  - Interaction of flavonoids and intestinal facilitated glucose transporters.
AB  - The intestinal facilitated glucose transporter, GLUT2, is a high-turnover
      transport system and is important to handle the large transepithelial substance
      flux. Since intestinal GLUT2 is normally located at the basolateral side, glucose
      uptake in the presence of flavonoids was measured using basolateral membrane
      vesicles (BLMV) isolated from the rat jejunum to investigate the interaction
      between flavonoids and intestinal facilitated glucose transporters. In addition,
      basolateral uptake of flavonoids was studied in Caco-2 cells. As a result, in the
      BLMV study most flavonoids (glycosides or aglycones) at 0.1 mM inhibited glucose
      uptake in BLMV; epicatechin gallate (ECG) showed the highest inhibitory activity
      (about 33%), followed by quercetin 3-O-glucoside (Q3G), fisetin and gossypin
      (about 25-28% inhibition). The dose-response study showed that the IC50 values
      for ECG and Q3G on glucose uptake in BLMV were 294+/-89 microM and 357+/-52
      microM, respectively. Kinetic analyses showed that ECG and Q3G competitively
      inhibited glucose uptake in BLMV with inhibition constants (Ki) of 332+/-42
      microM and 404+/-45 microM, respectively. In Caco-2 cells, basolateral uptake of
      Q3G was significantly inhibited by phloretin, a GLUT2 inhibitor (0.40+/-0.05 vs.
      0.24+/-0.03 nmole/mg protein without aand with phloretin, respectively). On the
      other hand, phloretin did not show inhibitory activity on basolateral uptake of
      ECG in Caco-2 cells (1.26+/-0.05 vs. 1.22+/-0.07 nmole/mg protein without and
      with phloretin, respectively). The data showed that the intestinal facilitated
      glucose transporter recognizes a variety of flavonoids with or without
      conjugation. In addition, GLUT2 can be responsible for the transport of Q3G
      across the intestinal basolateral membrane.

PMID- 17511060
TI  - The effect of the volatile oil from ginger rhizomes (Zingiber officinale), its
      fractions and isolated compounds on the 5-HT3 receptor complex and the
      serotoninergic system of the rat ileum.
AB  - A contribution of the volatile oil from ginger rhizomes (Zingiber officinale
      Roscoe) on inhabiting the 5-HT3 receptor complex had been shown. In the present
      study a possible interaction of some compounds of the volatile oil with the 5-HT3
      receptor system expressed in N1E-115 cells and with the serotoninergic system of
      the rat ileum was investigated. The volatile oil was obtained by steam
      distillation and fractionated using a silica gel column resulting in five
      fractions. Compounds of the fractions were identified by GC-MS. The influence of
      the volatile oil, its fractions and pure components on serotonin-induced
      [14C]guanidinium influx into N1E-115 cells was measured indicating the inhibitory
      interaction with the 5-HT3 receptor channel system. Most potent inhibitors of
      cation influx were the volatile oil, fraction 4, beta-pinene, terpinolene, alpha
      copaene and alpha-phellandrene. The volatile oil and fractions 1 and 4 were not
      able to significantly influence either serotonin (10 microM)-induced maximum
      contraction of the rat ileum or the second phase of the biphasic contraction 2.5
      min after serotonin addition. However, beta-pinene, terpinolene and alpha
      phellandrene reduced both contractions. In conclusion, the volatile oil and
      distinct compounds such as terpinolene, beta-pinene and alpha-phellandrene
      interact with 5-HT3 receptor channel system and possess an antispasmodic effect
      at the rat ileum.

PMID- 17511061
TI  - Use of exenatide for weight loss in patients with diabetes.

PMID- 17511062
TI  - [Cardiac failure: introduction].

PMID- 17511063
TI  - [Changes of the concept of heart failure].

PMID- 17511064
TI  - [Recent advances and future issues in basic research of heart failure].

PMID- 17511065
TI  - [Progress in clinical practice for heart failure and future problems].

PMID- 17511066
TI  - [Current view and prospects of gene therapy for heart failure].

PMID- 17511067
TI  - [The overview: the diagnosis and the treatment of heart failure in elderly].

PMID- 17511068
TI  - [The Japanese Cardiac Registry in CHF (JCARE) study].

PMID- 17511069
TI  - [Chronic Heart Failure Analysis and Registry in the Tohoku District: the CHART
      study].

PMID- 17511070
TI  - [Molecular mechanisms of chronic heart failure].

PMID- 17511071
TI  - [Phospholamban].

PMID- 17511072
TI  - [Apoptosis and autophagy in cardiomyocytes].

PMID- 17511073
TI  - [Angiotensin II and heart failure].

PMID- 17511074
TI  - [Nitric oxide].

PMID- 17511075
TI  - [Intracellular signaling pathways for cardiac hypertrophy: ERK, JAK-STAT, S6
      kinase].

PMID- 17511076
TI  - [Roles of TNFalpha in failing myocardium].

PMID- 17511077
TI  - [IL-1beta, IL-6, IL-10].

PMID- 17511079
TI  - [The mechanism of ROS production in cardiac muscle].

PMID- 17511078
TI  - [Toll-like receptor (TLR)].

PMID- 17511080
TI  - [Endothelial dysfunction and oxidative stress in chronic heart failure].

PMID- 17511082
TI  - [Genetic polymorphism in heart failure].

PMID- 17511081
TI  - [The cytoskeleton and related proteins mutation in the myocardium].

PMID- 17511083
TI  - [Cardiomyocyte hypertrophy].

PMID- 17511084
TI  - [Cardiovascular dynamics in heart failure].

PMID- 17511085
TI  - [Abnormal peripheral circulation in patients with heart failure].

PMID- 17511086
TI  - [Myocardial ischemia].

PMID- 17511087
TI  - [Renin-angiotensin-aldosterone system].

PMID- 17511088
TI  - [Left sided heart failure and right sided heart failure].

PMID- 17511090
TI  - [History and perspective of heart failure diagnosis: review article].

PMID- 17511089
TI  - [Classification of heart failure].

PMID- 17511091
TI  - [Clinical diagnosis of heart failure].

PMID- 17511092
TI  - [Chest X-ray].

PMID- 17511093
TI  - [Cardiac sympathetic nerve function assessed by 12I-labeled
      metaiodobenzylguanidine (MIBG) scintigraphic imaging].

PMID- 17511094
TI  - [NT-proBNP].

PMID- 17511095
TI  - [Cardiac troponin].

PMID- 17511096
TI  - [Exercise test for heart failure patients].

PMID- 17511097
TI  - [ESC guidelines].

PMID- 17511098
TI  - [The management of acute heart failure: an overview].

PMID- 17511099
TI  - [Management of chronic heart failure].

PMID- 17511100
TI  - [Val-HeFT trial--evidence for valsartan in heart failure].

PMID- 17511101
TI  - [J-ELAN study (effect of losartan and amlodipine on left ventricular diastolic
      function in patients with mild-to-moderate hypertension)].

PMID- 17511102
TI  - [X-SOLVD].

PMID- 17511103
TI  - [COMET: metoprolol].

PMID- 17511104
TI  - [The Carvedilol and ACE-Inhibitor Remodelling Mild Heart Failure Evaluation
      Trial].

PMID- 17511105
TI  - [Gastrojejunostomy versus endoscopic stent placement as palliative treatment of
      malignant stenosis of the duodenum: overview of advantages and disadvantages on
      the basis of a literature study].

PMID- 17511106
TI  - [Bias of results in clinical research due to method of informed consent].

PMID- 17511107
TI  - Are we born moral?
AB  - Reviews of: Hauser, Marc D. Moral minds: how nature designed our universal sense
      of right and wrong. (New York: Ecco, 2006); and Waal, F.B.M. de. Primates and
      philosophers: how morality evolved. (Princeton, N.J. : Princeton University
      Press, 2006).

PMID- 17511108
TI  - [The history of the agricultural economics department at the Agricultural
      University of Godollo, 1920-2001].

PMID- 17511109
TI  - Dream of scientific brotherhood.
AB  - Review of: Gribbin, John. The fellowship: Gilbert, Bacon, Harvey, Wren, Newton,
      and the story of a scientific revolution. (New York: Overlook, 2005). Focusing on
      the history of the Royal Society.

PMID- 17511110
TI  - Hydrogel-Based BioMEMS platforms for smart drug delivery.
AB  - Environmentally sensitive hydrogels offer unique opportunities for smart flow
      control in microfluidic systems. These tangled networks of cross-linked polymer
      chains, immersed in a solvent, manifest a reversible and abrupt swelling phase
      transition in response to changes in environmental factors such as glucose
      concentration, pH, electric field, temperature, and light. This transition often
      results in an abrupt volume change (swelling or shrinking) that can be as large
      as 1000 fold or more. Because of this property, hydrogels are attractive
      candidates as components microactuators operating in aqueous media such as body
      fluids. For example, the volume phase transition in these materials can be
      harnessed in smart microfluidic components used for implantable drug delivery
      systems. In this talk, we will discuss several hydrogel-actuated MEMS-based
      microdevices for smart microflow control developed in out laboratories at th
      University of Minnesota. These include: 1) a hydrogel-actuated microvalve with a
      porous back-plate, 2) a hydrogel-gated smart flow controller, 3) a microvalve
      with double side tethered structure for the entrapment of hydrogel, and 4) a
      wireless passive glucose transponder. Our emphasis is particularly on lightly
      crosslinked poly(methacrylamidophenylboronic acid-co-acylamide) hydrogel that
      swell monotonically at pH 7.4 with exposure to increasing concentration of
      glucose.

PMID- 17511111
TI  - Utilisation of pathology procedures.

PMID- 17511112
TI  - Enteropathy-type T-cell lymphoma.
AB  - Session 7 of the Society for Hematopathology/European Association for
      Haematopathology Workshop was devoted to case presentations and discussion of
      enteropathy-type T-cell lymphoma (ETL) and other T-cell lymphomas involving the
      gastrointestinal tract. ETL is a rare type of T-cell lymphoma, often associated
      with a history of celiac disease, that usually arises in the jejunum but can
      involve other gastrointestinal tract sites (eg, stomach and colon). As the cases
      submitted illustrate, there are 2 histologic groups of ETL that correlate with
      clinical and immunophenotypic features. Pleomorphic-anaplastic ETL is usually
      associated with a history of celiac disease and histologic evidence of
      enteropathy and is most often CD56-. Monomorphic ETL often occurs without a
      history of celiac disease, has variable histologic evidence of enteropathy, and
      is usually CD56+. Comparative genomic hybridization has shown recurrent
      chromosomal gains and losses that are characteristic of ETL and uncommon in other
      T-cell lymphomas, providing useful ancillary data for the diagnosis of ETL.

PMID- 17511113
TI  - Anaplastic Large Cell Lymphoma.
AB  - Session 8 of the 2005 Society of Hematopathology/European Association for
      Haematopathology Workshop was devoted to anaplastic large cell lymphoma (ALCL).
      Most cases submitted were anaplastic lymphoma kinase (ALK)+ ALCL highlighting
      unusual clinical settings, histologic variants, and variant translocation
      partners. Cases submitted as ALK- ALCL emphasized the immunohistochemical overlap
      with classical Hodgkin lymphoma (eg, CD15+/CD30+). It was also clear that
      consensus histologic and immunohistochemical criteria for the diagnosis of ALK
      ALCL are lacking. Many expressed the opinion that ALK-ALCL is not a distinct
      entity at the immunophenotypic or genetic level and is better designated as
      peripheral T-cell lymphoma (PTCL), unspecified. Others suggested that the
      histologic features of ALK-ALCL are distinctive nevertheless and that this
      diagnosis has meaning that is lost by designating these neoplasms as PTCL,
      unspecified. This session also included CD30+ anaplastic lymphomas involving skin
      in which the differential diagnosis included cutaneous ALCL and systemic ALK
      ALCL.

PMID- 17511114
TI  - The CSI effect: the truth about forensic science.

PMID- 17511115
TI  - The learning curve in pancreatic surgery.
AB  - BACKGROUND: Pancreatic surgery is technically complex. We hypothesized that a
      learning curve existed for pancreaticoduodenectomy even for surgeons who had
      completed their training. METHODS: During 1990 to 2004, we studied 650
      consecutive patients who underwent pancreaticoduodenectomy by 3 surgeons who
      began their attending careers at 1 center. Operative time, estimated blood loss
      (EBL), length of hospital stay (LOS), and the status of resection margins (for
      pancreatic adenocarcinoma) were analyzed. The chi2, independent t test and Mann
      Whitney U test were used to evaluate differences in categorical, normally
      distributed continuous, and non-normally distributed continuous variables,
      respectively. Using serial groups of 30 cases, median operative time, EBL, and
      LOS were calculated and the trend over time modeled using third-order polynomial
      equations. Trends in retroperitoneal margin positivity (R0/R1) were assessed.
      RESULTS: From the first 60 cases per surgeon to the second 60 cases per surgeon,
      the median EBL dropped (1100 vs 725 mL, P < .001), operative time decreased (589
      vs 513 minutes, P < .001), and LOS decreased (15 vs 13 days, P = .004). The
      proportion of microscopically positive or suspicious margins also decreased from
      the surgeons' first 60 cases each to the second 60 cases (30% vs 8%, P < .001).
      Extended analysis of a single surgeon's cases suggested that additional
      experience provided further incremental improvement (P < .001). CONCLUSIONS:
      Pancreaticoduodenectomy has an inherent learning curve. After 60 cases, surgeons
      achieved significantly decreased EBL, operative time, and LOS, and carried out
      more margin-negative resections. Improvement in measured outcomes continues
      during the operative career.

PMID- 17511116
TI  - A tribute to Aaron Lerner.

PMID- 17511117
TI  - Battling bacteria for enhanced oral healthcare.

PMID- 17511118
TI  - Simple guidelines for aesthetic success with composite resin--Part I: anterior
      restorations.
AB  - Composite restorations have the advantage of being created in the dental office,
      which can lead to beautiful, natural aesthetics. Laboratory technicians tend to
      spend minimal time with the patient and reconstruct the restoration based on
      information provided by the clinician. Dentists, however, are at a great
      advantage, as they can refer to the surrounding tooth structure when building the
      restoration. Part I of this article will discuss various guidelines for treating
      anterior teeth using direct resin restorations, while Part II will address
      posterior restorations.

PMID- 17511119
TI  - The evolving e-practice. Improving patient health via digital radiography.

PMID- 17511120
TI  - Preheating composite resin: a clinical perspective.

PMID- 17511121
TI  - Immediate loading of narrow-diameter implants with overdentures in severely
      atrophic mandibles.
AB  - Oral rehabilitation using two to four implants to support mandibular overdentures
      has been shown to have success rates of approximately 96% with implants placed in
      a one- or two-stage procedure. The purpose of this study is to evaluate 10
      consecutive cases of immediately loaded, narrow-diameter implants (NDIs) as
      support for overdentures in severely atrophic mandibles, and report on
      implant/prosthetic survival rates and patient satisfaction. Overall implant and
      prosthetic survival rates were 94.1% and 100%, respectively.

PMID- 17511122
TI  - Fabricating a fixed partial denture with CAD/CAM technology.

PMID- 17511123
TI  - A technique to improve the retention of resilient liner materials to dentures.

PMID- 17511124
TI  - Multidisciplinary management of anterior diastemata: clinical procedures.
AB  - Anterior diastemata may compromise the harmony of a patient's smile.
      Consideration of etiologic factors, previous gingival conditioning, and
      individual treatment planning are essential in the proper management of anterior
      diastemata. An integrated orthodontic-restorative approach may enhance the
      aesthetic results when orthodontic therapy itself is not feasible. This article
      presents integrated orthodonticrestorative solutions of anterior diastemata,
      associated with the conditioning of the gingival tissue with composite resin, and
      discusses the most relevant aspects related to their etiology and treatment
      planning.

PMID- 17511125
TI  - Majority rule.

PMID- 17511126
TI  - "The NTI appliance for TMD and headache therapy".

PMID- 17511127
TI  - "The NTI appliance for TMD and headache therapy".

PMID- 17511128
TI  - Unregulated herbal products: potential interactions and side effects in dental
      patients.

PMID- 17511129
TI  - Maxillary lateral incisor implants: planning with the aid of orthodontics.
AB  - This article has discussed six guidelines for managing adolescent orthodontic
      patients who are missing their maxillary lateral incisors and will require
      implants to replace these teeth. The space for the crown and implant, the space
      between the apices of the roots of the central incisor and canine, the
      possibility of implant site development, the effect of space opening on the
      integrity of the adjacent papillae, the impact of altered passive eruption, and
      the method for determining the age of implant placement have been discussed in
      detail. The intent of this article has been to emphasize the importance of
      interdisciplinary decision-making when planning implants in young adolescent
      patients who are congenitally missing their maxillary lateral incisors.

PMID- 17511130
TI  - Creating a usable computer-based clinical dental system for the operatory.

PMID- 17511131
TI  - Shape up your life--beyond ergonomics.

PMID- 17511132
TI  - Five product trends you can't ignore.

PMID- 17511133
TI  - Oral and maxillofacial pathology case of the month. Neurofibroma.

PMID- 17511134
TI  - [Discovery strategy for effective and active constituents of Chinese material
      medica based on processes of metabolism and disposition in intra-body].
AB  - Chinese material medica is the natural therapeutic agent used under the guidance
      of the theories of traditional Chinese medicine. Its sources are mainly derive
      from plants, some derive from animals and minerals, and a few derive from
      chemical drugs and biologic products. It was made up into a colossal complexed
      system because it's diversity of biological sources, ecological environments,
      chemical structures, processing methods, processes of metabolism and disposition
      in intra-body, biological activity and clinical use, and involved a lot of
      scientific problems. The elucidation of the effective and active constituents is
      a basic and scientific problem to clarify complexed system of Chinese material
      medica. Along with research progressing of processes of metabolism and
      disposition of Chinese material medica in intra-body and metabonomics, a new and
      rapid-developing technology, the discovery strategy for effective and active
      constituents of Chinese material medica based on the processes of metabolism and
      disposition would be made up, which will provide a new methodology and pathway to
      clarify of complexed system of Chinese material medica.

PMID- 17511135
TI  - [Research progress of microparticles as drug delivery system for traditional
      Chinese medicine].
AB  - Microparticle preparation, a new drug delivery system based on microencapsulation
      technique, includes micro-spheres and microcapsules. Recently, this new drug
      delivery system has been applied in developing new dosage forms for the
      traditional Chinese medicine (TCM). TCM microparticles can perform several sound
      characteristics and functions which are currently unavailable in TCM
      preparations, such as controlled release, effect of targeting, increasing
      bioavailability or low toxicity. This makes it possible that TCM may exert much
      higher therapeutic efficacy and show lower side-effects as well. Although the
      studies on TCM microparticles are still in the beginning stage, microparticle
      preparation of TCM has given rise to comprehensive attention and will have a
      wonderful prospect. The progress in this field is reviewed in this article.

PMID- 17511136
TI  - [Plant hydroponics and its application prospect in medicinal plants study].
AB  - This article introduced the theorem and method of hydroponics. Some examples of
      studies in agriculture and forestry were presented, the effects of elements,
      environmental stress and hormones on physiology of medicinal plants by using
      hydroponics were analyzed. It also introduced the feasibility and advantage of
      hydroponics in intermediate propagation and allelopathy of medicinal plant. And
      finally it made the conclusion that the way of hydroponics would be widely used
      in medicinal plant study.

PMID- 17511137
TI  - [Study on seed quality test and quality standard of Platycodon grandiflorum].
AB  - OBJECTIVE: To study quality test, and establish quality classification standard
      of Platycodon grandiflorum. METHOD: The seed quality and planting quality of P.
      grandiflorum from different producing areas and in different growing years were
      measured. RESULT AND CONCLUSION: The range of seed purity, weight per 1000 seeds,
      seed moisture content,seed viability were determined and the primary seed quality
      classification standard was established.

PMID- 17511138
TI  - [Studies on diversity of quality of Forsythia suspensa].
AB  - OBJECTIVE: To study on diversity of quality of Forsythia suspense collected from
      different regions. METHOD: The hundred-seed weight of shucks was analyzed by the
      method of hundred grain mass. The thousand-seed weight of seeds was analyzed by
      the method of thousand grain mass. The contents of the active components in
      shucks and seeds were determined by HPLC. RESULT: The hundred-seed weight of
      shucks, the thousand-seed weight of seeds and the contents of the active
      components in the shucks and seeds from different regions were significantly
      different. CONCLUSION: The quality of F. suspense from different regions is not
      consistant.

PMID- 17511139
TI  - [Circulated extraction of flavonoids from Glechoma longituba by ultrasonic wave].
AB  - OBJECTIVE: To investigate the optimum condition of extraction for the flavonoids
      in Glechoma longituba by ultrasonic wave. METHOD: Using orthogonal test, the
      effects of ultrasonic power, ultrasonic time, extraction temperature and solvent
      concentration were considered, the comprehensive evaluation was guided by the
      content of the flavonoids determined by ultraviolet spectrophotometer. RESULT:
      The optimum condition was as follow: ultrasonic power; 800 W, ultrasonic time 90
      min, extraction temperature 40 degrees C, solvent concentration 65%. The
      flavonoids concent is 5.228%. CONCLUSION: Using ethanol as solvent, circulated
      extraction of the flavonoids from G. longituba with ultrasonic wave is feasible
      with the optimum conditions in low temperature, short time and high production
      yield.

PMID- 17511140
TI  - [Preparation and evaluation of sustained-release microsphere of Sanguis Draconis
      in vitro].
AB  - OBJECTIVE: To prepare sustained-release microsphere containing extract of Sanguis
      Draconis and to measure its dissolution in vitro. METHOD: Sustained-release
      microsphere was prepared with polylactic acid (PLA) as carriers using the oil-in
      water (O/W) emulsion solvent evaporation method. The powder particle's
      characteristics of sustainded-release microsphere were evaluated comprehensively,
      and its dissolution characteristics in vitro were studied. RESULT: The
      microsphere was round and its surface was smooth, drug-loading rate was 21.97%
      and the entrapment rate was 55.76%, the accumulative release percentage was 76.
      71% in 16 hours. CONCLUSION: The sustained release effect of Sanguis Draconis
      microspheres was formed with potentially wide applications.

PMID- 17511142
TI  - [Influence of permeation enhancers on transdermal permeation of anemonin].
AB  - OBJECTIVE: To investigate the effect of different permeation enhancer on
      transdermal permeation of anemonin through human skin. METHOD: The permeation
      experiments were performed using human skin on modified Franz diffusion cells in
      vitro. The concentrations of anemonin in receptor compartment at specified time
      points were determined by HPLC. The steady flux and the cumulative quantity of
      anemonin through skin were calculated. RESULT: The flux of anemonin permeating
      through human skin from 30% ethanol, 50% ethanol solution and a combination of 3%
      laurocapm -5% polysorbate 20 and 30% ethanol -3 % laurocapm -5% polysorbate 20 of
      anemonin was (9.30 +/- 0.32), (18.56+/-0.58), (7.29+/-0.35), (13.77+/-0. 16)
      microg x cm(-2) x h(-1) and 7.9, 15.9, 6.2, 11.8 times higher than from saturated
      water solution respectively. CONCLUSION: Ethanol and laurocapm can remarkably
      improve the transdermal permeation of anemonin and the anemonin have the
      potential to be developed to new transdermal preparation.

PMID- 17511141
TI  - [Optimization of formulation matrix proportion and preparation technology of
      realgar floating tablets for gastric retention by uniform design and correlation
      analysis].
AB  - OBJECTIVE: To optimize the different components proportions of the Realgar
      floating tablets for gastric retention by uniform design and correlation
      analysis. METHOD: With the different dosage of hydroxypropyl methyl cellulose
      (HPMC) as the tablets frame matrix, uniform design and correlation analysis were
      used to optimize the best component proportions of formula, and to measure the
      dissolution of the tablets in vitro. RESULT: Dissolution of the tablets in vitro
      was conformed to the expectation of experiment. The drug-release mechanism was by
      diffusion and corrosion at the same time. CONCLUSION: The Realgar floating
      tablets for gastric retention achieved the goal of design, which demand sustained
      release and safety.

PMID- 17511143
TI  - [Study on separation and purification of total alkaloids and mesaconitine with X 
      5 macroporous resin].
AB  - OBJECTIVE: To study systematically the factors which affect separation and
      purification of the total alkaloids and mesaconitine with X -5 macroporous resin.
      METHOD: With the content of the total alkaloids and mesaconitine as parameters,
      the optimum condition of absorption and elution were studied in the process of
      the purification with X -5 macroporous resin. RESULT: The X - 5 macroporous resin
      yielded the best separating efficiency when the concentration of the extracted
      solution was 1 g raw material per 1 mL, pH 12.0, the absorptive time of 6 hour
      and the volume of 95% ethanol (7BV pH 8) as the eluant; X -5 macroporous resins
      was used five times in a reproducible way. The rate of extraction and content of
      the total alkaloid were 80% and 30% respectively after purification with X - 5
      macroprous resin. CONCLUSION: The method can increase the purity of mesaconitine
      and total alkaloids.

PMID- 17511144
TI  - [New cerebroside from leaves of pineapple].
AB  - OBJECTIVE: To study the chemical constituents of the leaves of pineapple. METHOD:
      Chromatographic methods were used to isolate compounds from the leaves of
      pineapple and spectral methods were used to identify the structures of the
      isolated compounds. RESULT: Compound 1 was isolated from the leaves of pineapple.
      It was identified as 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 11E)-2-[(2(R)
      hydroxydocosanoyl) amido]-4, 11-hexadecanediene-1, 3-diol. CONCLUSION: Compound 1
      was a new compound.

PMID- 17511145
TI  - [Study on chemical constituents of Myricaria paniculata I].
AB  - OBJECTIVE: To study the chemical constituents of Myricaria paniculata. METHOD:
      Silica gel column chromatography was used to separate and purify the chemical
      constituents, and the structures were elucidated by spectral analysis. RESULT:
      Four compounds were isolated from the petroleum ether soluble portion, identified
      as 28-aldehyde-taraxerenone (1), 28-hydroxy-taraxerenone (2), epi-friedelanol
      (3), 4-methyl stigmast-7-en-3-ol (4). Three compounds were isolated from the
      EtOAc soluble portion, identified as morelloflavone (5), methyl 3, 5-dihydroxy-4
      methoxybenzoate (6), 3-hydroxy-4-methoxy cinnamic acid (7). CONCLUSION: All of
      these compounds were isolated from the genus for the first time.

PMID- 17511146
TI  - [Studies on chemical constituents from roots of Cudrania cochinchinensis].
AB  - OBJECTIVE: To study the chemical constituents from the roots of Cudrania
      cochinchinensis. METHOD: The chemical constituents of C. cochinchinensis were
      isolated and purified by silica gel, polyamide column chromatography, Their
      structures were identified on the basis of spectroscopic data. RESULT: Six
      compounds were isolated and identified. Their structures were established as 3,
      5, 7, 4"-tetrahydroxyflavanone-7-O-(6"-acetyl)-glucoside (1), 3, 5, 7, 4'-tetra
      hydroxyflavanone-7-O-glucoside (2), 2', 4', 5, 7-tetrahydroxy-6
      prenyldihydroflavanone (3), 5, 7, 4'-trihysdroxy-6-prenylisoflavanone (4), 1, 3,
      5, 6-tetrahydroxyxanthone (5), stilbene-2, 4, 3', 5'-tetraol (6). CONCLUSION:
      Compound 1 was isolated from this genus, while compounds 4 and 5 were isolated
      from this plant for the first time.

PMID- 17511147
TI  - [Studies on chemical constituents of Salsola collina].
AB  - OBJECTIVE: To study the chemical constituents of Salsola collina. METHOD: The
      EtOH extract from the whole plant of S. collina were isolated and purified by
      column chromatography. These compounds were identified by their physical
      properties and spectroscopic data. RESULT: Eleven compounds were isolated and
      identified as ferulic acid (1), p-coumaric acid (2), salicylic acid (3), tricin
      (4), selagin (5), acanthoside D (6), tricin -7-O-beta-D-glucopyranoside (7),
      tricin-4'-O-beta-D-apioside (8), isorhamnetin-7-O-beta-D-glucopyranoside (9),
      isorhamnetin-3-O-beta-D-glucopyranoside (10), isorhamnetin-3-O-alpha-L
      arabinopyranosyl (1-->6) -beta-D-glucopyranoside (11). CONCLUSION: wherein
      compound 1, 2, 3, 5, 6 and 9 were isolated from the Salsola for the first time.

PMID- 17511148
TI  - [Effect of combination glycyrrhiizin and triptolide on TNF-alpha and IL-10 in
      serum of collagen induced arthritis rats].
AB  - OBJECTIVE: To observe the effects of combination therapy with glycyrrhizin (GL)
      and triptolide (TP) on collagen-induced arthritis (CIA) rats. METHOD: Sixty male
      SD rats were randomly divided into 6 groups: the model group, the TP group, the
      GL group, and combination 1, 2, 3 groups. The models were induced by collagen
      type II. The arthritis index (AI) and the edema rate were detected as curative
      effect, and the level of antibodies to collagen, TNF-alpha and IL-10 were
      measured by ELISA. RESULT: The combination therapy with GL and TP significantly
      reduced the paw edema and arthritis index of CIA rats (P <0. 01 ), and the
      combination therapy can increase the level of IL-10, while decrease the level of
      TNF-alpha, and the level of antibodies to collagen decreased too (P <0.05, P
      <0.01). CONCLUSION: Combine 26.78 mg x kg(-1) GL with 13.40 microg x kg(-1) TP
      can significantly inhibited the CIA, and the effect equal to the dosage of 17. 86
      microg x kg(-1) TP. It supports the possible of GL in combination with TP to
      reduce the dose and side effects related to TP.

PMID- 17511149
TI  - [Studies on pharmacokinetics of diosmin in rats].
AB  - OBJECTIVE: To establish a HPLC method for the determination of diosmin in Rats
      plasma and to study the pharmacokinetics of diosmin in Rats. METHOD: Rats were
      given diosmin with 3 doses as 225, 325, 425 mg x kg(-1). Blood samples were
      collected at different times after oral administration. The plasma concentration
      of diosmin was determined by HPLC, and the pharmacokinetics parameters were
      calculated by 3p97 program. RESULT: The typical equation of diosmin in rats
      plasma was Y = 3.05 x 10(-3) C + 1.55 x 10(-3), the calibration curves of diosmin
      was linear in the range from 0.5-100 microg x mL(-1) (R =0. 996 4). The lowest
      concentration of diosmin in plasma was 0. 2 g x mL(-1). Its recoveries was more
      than 85%, and the interday and intraday precision, which was expressed as RSD,
      were all less than 15%. After 3 doses oral administration of diosmin in rats, the
      mean plasma concentration-time curves were found to fit one compartment model,
      and the main pharmacokinetics parameters were obtained. CONCLUSION: It is first
      time to establish the HPLC method to determine the concentration of diosmin in
      rats plasma, and the method described in this report has high sensitivity and
      selectivity, and it was suitable for pharmacokinetics studies of diosmin. The
      internal process of diosmin in rats is fit to one compartment model.

PMID- 17511150
TI  - [Comparison of properties of Mahuang decoction and Maxing Shigan decoction based
      on biothermodynamics].
AB  - OBJECTIVE: To probe into the objectivity and authenticity of four properties
      beteen Mahuang decoction and Maxing Shigan decoction from biothermodynamics.
      METHOD: The power-time curves of growth of Staphylococcus aureus at different
      concentrations between Mahuang decoction and Maxing Shigan decoction were
      determined by TAM Air Isothermal Calorimeter. The growth rate constants of
      promotive and inhibitory actions were calculated. Moreover, the difference of
      properties beteen Mahuang decoction and Maxing Shigan decoction was analyzed from
      the point of view of TCM theory. RESULT: Both the Mahuang decoction and Maxing
      Shigan decoction could inhibit the growth and metabolism of Staphylococcus
      aureus. The k and Pm were decreased with the mass increase of the decoction.
      However, inhibitory activity of Mahuang decoction with warm property was weaker
      than that of Maxing Shigan decoction with cool property. Moreover, Mahuang
      decoction decreased heat output in growth metabolism more weakly than Maxing
      Shigan decoction. There was a stable difference between them. CONCLUSION:
      Studying on biothermodynamics can show the difference of four properties of
      Traditional Chinese Medicine. So, it provides a new and useful means for the
      study of the properties of traditional Chinese medicine.

PMID- 17511151
TI  - [Effect of emodin on proliferation and differentiation of rat preadipocytes].
AB  - OBJECTIVE: To study the effect of emodin (EMO) on the proliferation and
      differentiation of rat preadipocytes. METHOD: Separating and culturing rat
      preadipocytes, grouping the wells that preadipocytes were growing according to
      certain concentration such as 0, 5, 10, 20, 40, 80, 160 micromol x L(-1)
      randomly, MTT spectrophotometry and flow cytometry (FCM) were adopted to
      determine the effect of EMO on proliferation of rat preadipocytes. The
      accumulation of TG (triglyceride) in adipocytes was assayed by oil red O
      staining, and the morphological changes of the adipocytes were determined by
      morphology observation. RESULT: EMO in the range of 20-160 micromol x L(-1) could
      inhibit the proliferation and differentiation of preadipocytes in a dose and time
      dependent manner, and induce apoptosis of preadipocytes in a certain degree.
      CONCLUSION: EMO should have a potential to serve as a fat-reducing drug.

PMID- 17511152
TI  - [Pharmacodynamic and toxicologic comparative study of crude and processed radix
      aristolochice].
AB  - OBJECTIVE: To study the accumulated toxic action to bandicoot of aqueous extract
      of crude and processed Radix Aristolochice and the pharmacodynamic action of
      aqueous and alcoholic extract of crude and processed Radix Aristolochice. METHOD:
      The LD50 of acute toxicity to mice and chronic accumulated toxicity to bandicoots
      of crude and processed Radix Aristolochice were observated. Intestinal and
      myokinetic influence of normal and revulsive hyperactive gastrointestinal
      motility of mice induced by neostigmine were observated by giving aqueous extract
      and alcoholic extract of crude and processed Radix Aristolochice. Relieving pain
      and eliminating inflammation to mice also were observated. RESULT: The LD50 of
      aqueous extract of crude and processed Radix Aristolochice were 146. 45, 846.06 g
      X kg(-1) (equivalently to crude drug) respectively by intragastric
      administration. Bandicoot' general condition, peripheral blood, serum, organic
      coefficient, histopathologic examination weren't obvious changes after 1 month
      administrating aqueous extract of crude and processed drug in three dose. Serum
      indicators-urea nitrogen, cholesterol total, alkaline phosphatase manifestly were
      heightened and some animals'hepatic cells, nephric tubules and mucosa emerged
      differently damage at histomorphology by giving crude high dose after 2 months.
      Above organs emerged different damage in crude middle and high dose and processed
      high dose after 3 months and serum indicators- creatinine, urea nitrogen
      manifestly were increased, the coefficients of liver, kidney and gaster
      manifestly were heightened. However, the toxicity of identical dose processed
      product was lower than that of crude one. Aqueous extract and alcoholic extract
      of crude and processed Radix Aristolochice could obviously inhibite normal and
      revulsive hyperactive gastrointestinal motility by neostigmine of mice, relieve
      pain in mouse, stretching and heat stimulation models and inhibite dimethyl
      benzene-induc mouse, auricle inflammation. Pharmacodynamic action wasnt obvious
      difference in same dose of crude product and processed one. CONCLUSION: Acute
      toxicity and chronic accumulated toxicity are stepped down after giving processed
      Radix Aristolochice, but pharmacodynamic effect wasn t lower. In pharmacodynamic
      effect, aqueous extract can't compare with alcoholic extract in same dose.

PMID- 17511153
TI  - [Effects of Rhaponticum uniforum polysaccharide on immune response of mice after
      antigen stimulation and their possible mechanisms].
AB  - OBJECTIVE: To study the effects of Rhaponticum uniforum polysaccharide on immune
      function in normal mice and the underlying mechanism. METHOD: SRBC and ovalbumin
      were employed as antigens to be injected to mice, respectively. Three doses of R.
      uniforum polysaccharide (50, 100, 200 mg x kg(-1) x d(-1)) were given orally for
      seven days. After the secondary immunization, the level of corresponding antibody
      and the concentration of serum IL-2, IFN-gamma were determined. RESULT: The
      levels of antibodies (anti-SRBC and anti-ovalbumin) and cytokines (IL-2 and IFN
      gamma) in median dose group of R. uniforum polysaccharide were all significantly
      higher than those in control groups (P <0.05). CONCLUSION: R. uniforum
      polysaccharide could enhance the immune function in normal mice.

PMID- 17511154
TI  - [Evaluation on phytoestrogen effects of ten kinds of Chinese medicine including
      flos carthami].
AB  - OBJECTIVE: To explore the phytoestrogenic effects of ten kinds of Chinese
      medicine including flos carthami, radix cyathulae, radix salviae miltiorrhizae,
      fructus ligustri lucidi, fructus lycii, radix clycyrrhizae, herba cistanches,
      herba epimedii, fructus psoraleae and semen cuscutae. METHOD: 240 female Kunming
      mice weighting 9 - 12 g were randomly divided into two main groups A and B. A
      group was divided into 12 small groups: 1 solvent control group, 1
      diethylstilbestrol control group and 10 Chinese medicine groups. B group was also
      divided into 12 small groups: 1 solvent control group, 1 diethylstilbestrol
      control group and 10 Chinese medicine antagonistic groups. Mice in ten
      antagonistic groups were administered both Chinese medicine and
      diethylstilbestrol everyday. After administered(op) for 4 days, blood was
      collected and serum was separated. The effect of the pharmacological serum on
      proliferation rate of MCF-7 (ER+) was analyzed by MTT-assay. RESULT: In A group,
      proliferation rates of MCF-7 cells treated with serum from eight Chinese medicine
      groups including flos carthami, radix cyathulae, radix salviae miltiorrhizae,
      fructus lycii, herba cistanches, herba epimedii, fructus psoraleae and semen
      cuscutae were coued markedly increase respectively. While serum from fructus
      ligustri lucidi group could markedly decrease the proliferation rate of MCF-7
      cells. In B group, the increased proliferation rate of MCF-7 cells caused by
      diethylstilbestrol was significantly reduced in seven Chinese medicine
      antagonistic groups including flos carthami, radix cyathulae, radix salviae
      miltiorrhizae, radix clycyrrhizae, herba epimedii, fructus psoraleae and semen
      cuscutae. While the increased proliferation rate could be markedly enhanced in
      herba cistanches group. CONCLUSION: Six kinds of Chinese medicine such as flos
      carthami, radix cyathulae, radix salviae miltiorrhizae, herba epimedii, fructus
      psoraleae and semen cuscutae show both estrogenic effects (when administered
      indepently) and antiestrogenic effects (when administered together with
      diethylstilbestrol). Such bidirectional effects depends on the internal estrogen
      level.

PMID- 17511156
TI  - [Illumination of pharmacoeconomics on Chinese herbal medicine inject].
AB  - This text emphasizes the present condition of the production and usage to Chinese
      herbal medicine inject, from the research angle of view of the pharmacoeconomics.
      Inquiry into the Chinese herbal medicine injects of the funds throw and throw in
      a funds and resources, the output of clinical health result and output a
      circumstance with social welfare, explicit the Chinese herbal medicine injected
      to take up a great deal of medicine health resources, but output not optimistic.
      Put forward the important meaning of pharmacoeconomics evaluation to Chinese
      herbal medicine inject that appears on market behind and carry on the main
      contents of the pharmacoeconomics evaluation thus.

PMID- 17511155
TI  - [Effection of compositie salviae dropping pill on hyperlipemia patients with
      phlegm and blood stasis syndrome].
AB  - OBJECTIVE: To explore the effect of compositie salviae dropping pill (CSDP) on
      hyperlipemia patients with phlegm and blood stasis syndrome. METHOD: Hyperlipemia
      patients were divided randomly into two groups. One group of 40 patients were
      treated by CSDP, another group of 41 patients were treated by simvastatin. The
      TC, TG, HDL-C, LDL-C, ApoA and ApoB levels, ALT, r-GT, IL-6, MDA level and SOD
      activity were determined before and after being treated. RESULT: After 3 months
      treatment, the TC, TG and LDL-C levels were obviously decreased in two groups (P
      <0.01, P < 0.05), there is no significant difference between the effective rate
      of two groups. The ALT, r-GT, IL-8 and MDA levels of treatment group were
      obviously decreased (P < 0.01, P < 0.05), while the ApoA level and SOD activity
      increased obviously in those patients (P <0.05, P <0.01, respectively). However,
      the ALT, r-GT, IL-6, MDA, HDL-C, ApoA level and SOD activity had no significant
      difference after treatment in control group. CONCLUSION: Our study suggest that
      CSDP have the function of falling serum lipid level without damaging liver
      function, its function of protecting liver function might related to its function
      of improving of anti-oxidation and decreasing of inflammation, the mechanism of
      CSDP disparting and removing phlem and blood stasis in the processes lipid
      metabolism need to be studied further.

PMID- 17511157
TI  - [Application of midline partial glossectomy for OSAHS].
AB  - OBJECTIVE: To evaluate the prospective effect of applying midline partial
      glossectomy with Uvulopalatopharyngoplasty in the treatment of OSAHS. METHOD: The
      data of 40 patients with OSAHS operated with midline partial glossectomy with
      UPPP were analyzed. RESULT: The follow-up polysomnography (6-month follow-up)
      revealed that the mean apnea and hypopnea index decreased from 62.39+/-21.68 to
      18.60+/-5.01 (P<0.01), and the mean minimal oxygen saturation (SaO2) increased
      from 64.40%+/-14.96% to 88.39%+/-9.21% (P<0.01). In general, 29 patients were
      with excellent curative effect, 8 with good effect, and 3 with bad effect. Total
      effective rate was 92.5%. CONCLUSION: The study confirms that the same-stage
      midline partial glossectomy with UPPP for OSAHS is a safe and effective
      procedure.

PMID- 17511158
TI  - [Preventive study of vocal scar after fiber laryngoscope surgery].
AB  - OBJECTIVE: To explore the importance and preventive measure of vocal scar after
      fiber laryngoscope surgery. METHOD: The preventive measures such as treatment of
      the pathogeny, voice exercise, adjustment of operative skill, vocal rest after
      operation and drug treatment for vocal scars in 350 patients with polyps of vocal
      cord, vocal nodules and vocal cyst after fiber laryngoscope surgery were adopted
      in order to reduce the rate of vocal scar. The rate of vocal scar was calculated
      and analysed to evaluate the effect of preventive measures two month later.
      RESULT: The incidence rate of vocal scar after fiber laryngoscope surgery was
      12.3%. And vocal scar was the main difficulty in vocalizing after operation.
      There is yet no specific treatment for vocal scar. Prevention is more important.
      Preventive measures should be carried out through the perioperative period, i.
      e., before, in and after the surgery. CONCLUSION: The prevention of vocal scar
      complication is very important in the perioperative period of fiber laryngoscope
      surgery. And as the preventive measures are adopted, the incidence rate of vocal
      scar will be significantly reduced.

PMID- 17511159
TI  - [The diagnosis and management of laryngotracheal stenosis in children].
AB  - OBJECTIVE: To evaluate the clinical etiopathogenesis, the diagnose and the
      treatment of laryngotracheal stenosis in children. METHOD: Six patients with
      laryngotracheal stenosis who had been surgically were reviewed. RESULT: Three
      cases of congenital laryngeal cyst, among 2 cases were treated by undertaken
      endoscopic, one case was treated by laryngofissure. One case with congenital
      laryngeal web was treated by undertaken endoscopic with CO2 laser resection. One
      case with congenital tongue base cyst was treated by direct laryngoscope with
      puncture. One case with congenital cricoiddysplasty was treated by
      laryngotracheotomy with stent. One case of traumatic granuloma of trachea was
      treated by fence-form tracheotomy and inserting T-shape tube. Four patients were
      successfully decannulated, one patient was cured, one patient were followed-up.
      CONCLUSION: The early diagnosis of laryngotracheal stenosis in children was
      important. The different methods of surgical used here for the laryngotracheal
      stenosis proved to be effective. The functions of laryngotracheal would been
      recovered with good voices and satisfactory airway.

PMID- 17511160
TI  - [Different characters of children with foreign body in respiratory tract and the
      clinical research].
AB  - OBJECTIVE: To explore the different character of children from 0 to 3 years old,
      understand their psychological features, give guidances about nurturing and
      educating children, and supply theoretical base for preventing problems of
      children behaviors. METHOD: Two hundred and fifty-one children patients from 0 to
      3 years old were surveyed from clinic of maternal and child health care with
      children character software and questionnaire. RESULT: Among all characters,
      32.3% children were easy and medium nurturing type, 31.1% easy nurturing type,
      23.1% difficult nurturing type, 7.5% slow startup and 6.0% difficult and medium
      type. CONCLUSION: Main character of children from 0-3 years old are easy and
      medium nurturing type and easy nurturing type. Children with different ages and
      sexes have different characters, so pertinent education and guidance should be
      given according to characters of different ages and sexes so as to improve their
      health.

PMID- 17511161
TI  - [Clinical therapeutic effect of obstructive sleep apnea hypopnea syndrome treated
      by uvulopalatopharyngoplasty].
AB  - OBJECTIVE: To investigate the therapeutic effect of obstructive sleep apnea
      hypopnea syndrome (OSAHS) by modified uvulopalatopharyngoplasty (UPPP). METHOD:
      Forty-nine cases of OSAHS were treated by modified UPPP, and followed-up on 6
      months, 1 year and 2 years after operation and carried out polysomnography (PSG)
      every time. RESULT: Therapeutic effect was evaluated by standard of Hangzhou
      (2002) . In 6 months, symptoms of snore, breath holding, headache and lethargy
      disappeared or reduced obviously, the total effective rate was 100%. In 12 and 24
      months, the effective rate was 95.92% and 91.84% respectively. CONCLUSION: This
      operation can enlarge venting area of palatopharyngeal cavity effectively and
      keep density of soft palate as well as the normal function of pharyngeal mucous
      membrane, and can also elevate operative effect and decrease postoperative
      complications.

PMID- 17511162
TI  - [Impact of adenotonsillectomy on quality of life in children with sleep
      disordered breathing].
AB  - OBJECTIVE: To compare improvement in quality of life after adenotonsillectomy in
      children with similar demographics but with either obstructive sleep apnea
      hypopnea syndrome (OSAHS) or with milder forms of sleep-disordered breathing
      (SDB). To evaluate the relationship between polysomnogram (PSG) results and
      disease-specific quality of life for children with obstructive sleep apnea 18
      item survey (OSA-18). METHOD: Children with SDB who were suspected of having
      OSAHS were enrolled. All study participants underwent overnight PSG using
      standardized techniques. The effectiveness of adenotonsillectomy for the relief
      of SDB was evaluated by using the OSA-18. Follow-up was assessed at 6-9 months.
      Preoperative and postoperative OSA-18 scores for each group of children (OSAHS
      and mild SDB) were compared. RESULT: The study population included 51 children
      with SDB, and 28 of them met PSG criteria for OSAHS, the other 23 of them without
      OSAHS. The clinical data in the two groups were similar. OSA-18 scores were not
      significantly different between children with and without OSAHS. The total OSA-18
      scores and the scores for all domains showed significant improvement after
      surgery for both groups of children (P<0.01). A comparison of mean difference in
      total and domain scores for the two groups of children was not significant
      (P>0.05). The domains of sleep disturbance, physical suffering and caregiver
      concerns showed significant association with PSG parameters (P<0.01). But no
      strong association was identified for OSA-18 total scores and other two domains
      (P>0.05). CONCLUSION: Both groups of children showed a dramatic improvement in
      quality of life after adenotonsillectomy and the degree of improvement was
      similar. Fortunately, surgical therapy with adenotonsillectomy was associated
      with marked improvement in quality of life for children with either OSAHS or mild
      SDB. However, the association between PSG findings and OSA-18 scores was only
      moderate.

PMID- 17511163
TI  - [The rule of lymphatic formation and the relationship between lymphatic formation
      and clinical pathological factors in supraglottic carcinoma].
AB  - OBJECTIVE: To investigate the rule of lymphatic formation and the relationship
      between lymphatic formation and clinical pathological factors in supraglottic
      carcinoma. METHOD: Immunohistochemistry method and automatic image analysis
      technique were applied to observe the lymphatic quantity and state in central
      carcinoma tissue, join tissue and normal larynx mucosa of supraglottic carcinoma.
      Analyze the rule and the correlation between lymphatic formation and T stage,
      differentiation, lymph metastasis. RESULT: The lumen-lymphatic formation was not
      seen in central carcinoma tissue. There are little lymphatic in normal larynx
      mucosa whereas many lymphatic formation in join area. The lymphatic density in
      join tissue is correlated with T stage, differentiation and lymph metastasis: T(1
      2) lower than T(3-4) and the difference is significant (P<0.01); The difference
      between high and middle differentiation is insignificant (P=0.212); High-middle
      differentiation lower than low differentiation and the difference is significant;
      No lower than N+ and the difference is significant (P<0.01). CONCLUSION: In join
      area, there are lymphatic formation both in carcinoma area and para-tumor area.
      Tumor cell can go to lymph nodes via this pathway. This conclusion provides
      theoretical basis for clinical utility of the anti-tumor medicines which
      inhibitable lymphatic formation. It can help surgeons forecast prognosis and
      select more effective treatment method to observe join lymphatic vessel quantity.

PMID- 17511164
TI  - [Efficacy of postoperation and the change of red blood cell/hemoglobin in
      patients with obstructive sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: In order to investigate the effect of UPPP in patients with OSAHS, the
      range of the soft palate excision and impersonality standard for improving low
      oxygen after UPPP. METHOD: A prospective study was designed to evaluate 34 adult
      patients with OSAHS and 27 adult ear patients who were not OSAHS. Blood routine
      and palatopharyngeal data in two groups were measured before operation and 15-20
      days after operation. And follow up 6 months. The data before and after operation
      were analysed in statistical method (t test). RESULT: Length of soft palate,
      distance of pharynx, distance of palate pharynx, red blood cell (RBC), hemoglobin
      (HGB), and hematocrit (HCT) were significantly different in normal and OSAHS
      group (independent t test, P<0.01). Their indexes were significantly different in
      OSAHS group before and after operation (paired-sample t test, P<0.01). Only HGB
      and the lowest SaO2 were negative correlation before operation in OSAHS group.
      The value is bigger for HGB and smaller for SaO2 (t test, P<0.01). Result of
      follow up 6 months (31 cases): The effective ratio of subjective improving was
      74.2%, and the total effective ratio was 96.8%. One case had reflux of
      nasopharynx. CONCLUSION: Severe OSAHS patients should be underwent synthesized
      treatment. It is daytime sleepiness that was improved the most obviously. Soft
      palate excision scope can't exceed 1.5 cm. HGB can be an impersonality index to
      assess hypoxemia and improvement of SaO2 after operation for OSAHS.

PMID- 17511165
TI  - [Clinical analysis of 42 extranodal non-Hodgkin's lymphoma originated on head and
      neck].
AB  - OBJECTIVE: To analyze clinical features and pathologic classification of
      extranodal non-Hodgkin's lymphoma (NHL) originated on head and neck and to afford
      experience in early diagnosis. METHOD: Retrospective study of clinical material
      of 42 NHI originated on head and neck, which were proved by pathologic diagnosis.
      RESULT: To divide all the patients into 3 groups according to the position of the
      disease. There is significant difference of definite diagnosis time between
      pathological changes in tonsil and nasal cavity (P<0.05). The same result takes
      place between tonsil and nasal sinuses (P<0.05). There is no significant
      difference of definite diagnosis time between affection in nasal sinuses and
      nasal cavity (P>0.05); To divide all the patients into 2 groups according to with
      or without systematic syndromes, there is no significant difference between the 2
      groups (P>0.05). CONCLUSION: The symptoms of extranodal NHL originated in head
      and neck have no specificity, meanwhile their malignant degree is high. The
      diagnosis time of affection in tonsil is shorter than that in nasal cavities and
      nasal sinuses. But with or without systematic syndromes is not related to
      diagnosis time. Pay attention to unilateral disease in head and neck is important
      and biopsy is crucial.

PMID- 17511166
TI  - [The correlation between ultrastructure of lymphatic capillary and neck lymph
      node metastasis laryngeal carcinoma].
AB  - OBJECTIVE: To study the correlation between ultrastructure of lymphatic capillary
      in pericancerous tissue and neck lymph node metastasis in laryngeal carcinoma.
      METHOD: Transmission electronic microscope was applied to observe and compare
      ultrastructure of lymphatic capillary in 8 normal laryngeal epithelial tissue and
      12 pericancerous tissue of laryngeal cancer. RESULT: Lymphatic capillary of
      pericancerous tissue was significantly dilated compared with normal laryngeal
      tissue. A large amount of endothelial cell junction was open and devoid of
      basement membrane. Some endothelial cells of lymphatic capillary were destroyed
      or broken completely. CONCLUSION: Ultrastructure of lymphatic capillary in
      pericancerous tissue is an important factor of laryngeal cancer metastasis
      through lymphatic system. This research offers theoretic basis for laryngeal
      carcinoma metastasis mechanism and prevention.

PMID- 17511167
TI  - [Expression and distribution of aquaporin 1 in laryngeal carcinoma].
AB  - OBJECTIVE: To detect expression level and distribution of aquaporin 1 (AQP1) in
      laryngeal carcinoma tissues and try to find out the significance about the
      mechanism of AQP1 in the invasion of laryngeal carcinoma. METHOD: Twenty cases of
      laryngeal carcinoma tissues and 15 cases of normal tissues beside tumors were
      acquired immediately after surgery. The expression and distribution of aquaporin
      1 in laryngeal carcinoma were examined by RT-PCR, western blot analysis and
      immunohistochemical technique. RESULT: AQP1 expresses on the capillary endothelia
      of laryngeal mucous lamina propria and laryngeal mucous glands of normal tissues
      and mainly on the capillary endothelia cells, tumor cells and cancer nests of
      laryngeal carcinoma tissues. AQP1 mRNA and protein expression level in laryngeal
      tumor tissues is remarkably stronger than that in normal tissues beside tumors.
      CONCLUSION: The expression of AQP1 was increased in laryngeal carcinoma tissues
      over normal laryngeal tissues. It suggests that the mechanism of AQP1 in
      laryngeal carcinoma etiopathogenesis needs to be studied.

PMID- 17511168
TI  - [Round window catheter placement with dexamethasone perfusion for intractable
      sudden sensorineural hearing loss].
AB  - OBJECTIVE: To investigate the efficacy of round window catheter placement with
      dexamethasone perfusion for 13 patients with intractable sudden sensorineural
      hearing loss (SSNHL). METHOD: Dexamethasone (2.5 mg) was perfused
      transtympanically through round window catheter by Micro-infusion pump. The
      perfusion was taken twice a day and continued for an hour each time, for a total
      of 7 days. RESULT: Thirteen patients have been followed up for 1 month. Five of
      them (38.5%) were demonstrated a 17-54 dB improvement in pure-tone threshold
      average (PTA). The other 8 patients (61.5%) had no effect. CONCLUSION: Round
      window catheter placement with dexamethasone perfusion is a cost-effective and
      useful treatment for SSNHL patients who had no effect through conventional
      therapy, although hearing thresholds of these patients had hardly improved to
      normal levels.

PMID- 17511169
TI  - [Hearing evaluation in children with congenital malformations of the external
      ear].
AB  - OBJECTIVE: To explore the clinical and audiological characteristics of children
      with congenital malformations of the external ear. METHOD: One hundred and ten
      patients with congenital malformations of the external ear ranged from 2002 to
      2006 were involved in this study. The mean age was one year and four months. The
      children were divided into three groups according to the appearance of the
      external ear. The first group consisted of 94 patients with auricle malformation
      and atresia of the external auditory meatus. The second group consisted of 8
      patients with abnormal external auditory meatus (no atresia) and auricle
      malformation. The other 8 patients only with auricle malformation were included
      in the third group. All children underwent ABR tests, while some of these
      children accepted DPOAE and Acoustic-immittance measurements. RESULT: (1) Severe
      abnormal results of ABR were observed in 79 abnormal ears (78.22%) in children of
      first group, while moderate or severe abnormal results of ABR were observed only
      in 8 opposite side ears (normal ears). (2) Sixty-two and a half percent (5 ears)
      of ears of the second group (8 ears) had severely abnormal ABR results. (3)
      Severe abnormal ABR results occurred in 44.44 percent (4 ears) of ears of the
      third group (9 ears). Moderate or severe abnormal results of ABR were not
      observed in the opposite side ears (normal ears) in second and third groups.
      CONCLUSION: Congenital malformations of the external ear is an important factor
      affecting children's hearing. Auditory nerve impairment can be observed in
      children with congenital malformations of the external ear.

PMID- 17511170
TI  - [The effects of small dose of intratympanic gentamicin injection on intractable
      Meniere's disease].
AB  - OBJECTIVE: To explore the efficacy of small dose of intratympanic gentamicin
      injection on intractable Meniere's disease. METHOD: Retrospectively study the
      efficacy of gentamicin intratympanic injection on intractable Meniere's disease.
      The end-point of treatment was determined based on bedside tests (Spontaneous
      Nystagmus test, Head shaking test and Head Thrust test), hearing tests, or the
      improvement of patients symptoms. RESULT: Nineteen patients with Meniere's
      disease were treated with intratympanic gentamicin injection. Vertigo control was
      achieved in 17 patients (89%). Of them, vertigo of 5 patients was successfully
      controlled after single injection. Eight patients need double injections and 4
      patients need the third injections to control the vertigo. Endolymphatic sac
      shunt was performed to 1 patient because he could not tolerate the fullness of
      ear due to injection. The remainder 2 patients with double injections showed no
      improvement of vertigo and rejected further treatment. Hearing was improved in
      two patients after gentamicin injection. Three patients complained of hearing
      loss after intratympanic gentamicin injection. The hearing of the other patients
      did not change. CONCLUSION: Three weeks after using small dose of gentamicin
      intratympanic injection to treat intractable Meniere's disease, it was determined
      whether more injections is required. The results showed that by using this
      approach, the vertigo could be effectively controlled and the risk of hearing
      loss following intratympanic gentamicin injection could be reduced.

PMID- 17511171
TI  - [Diagnostic value of high-resolution computed tomography imaging in congenital
      inner ear malformations].
AB  - OBJECTIVE: To observe the inner ear structure with volume rendering (VR)
      reconstruction and to evaluate the role of high-resolution computed tomography
      (HRCT) in congenital inner ear malformations. METHOD: HRCT scanning was performed
      in 10 patients (20 ears) without ear disease (control group) and 7 patients (11
      ears) with inner ear malformations (IEM group) and the original data was
      processed with VR reconstruction. The inner ear osseous labyrinth structure in
      the images generated by these techniques was observed respectively in the normal
      ears and malformation ears. RESULT: The inner ear osseous labyrinth structure and
      the relationship was displayed clearly in VR imaging in the control
      group,meanwhile, characters and degree of malformed structure were also displayed
      clearly in the IEA group. Of seven patients (11 ears) with congenital inner ear
      malformations, the axial, MPR and VR images can display the site and degree in 9
      ears. VR images were superior to the axial images in displaying the malformations
      in 2 ears with the small lateral semicircular canal malformations. The
      malformations included Mondini deformity (7 ears), vestibular and semicircular
      canal malformations (3 ears), vestibular aqueduct dilate (7 ears, of which 6 ears
      accompanied by other malformations) , the internal auditory canal malformation (2
      ears, all accompanied by other malformations). CONCLUSION: HRCT can display the
      normal structure of bone inner ear through high quality VR reconstructions. VR
      images can also display the site and degree of the malformations three
      dimensionally and intuitively. HRCT is valuable in diagnosing the inner ear
      malformation.

PMID- 17511172
TI  - [The management of high jugular bulb and its active bleeding during middle ear
      surgery].
AB  - OBJECTIVE: To study the incidence of high jugular bulb (HJB) in the patients with
      chronic otitis media and to explore the management of its active bleeding during
      middle ear surgery. METHOD: From January 2005 to August 2006, consecutive 287
      patients undergoing surgical intervention for chronic otitis media were
      retrospectively studied. The high resolution CT (HRCT) scan and the surgical
      technique for diagnosis and management of bleeding of jugular bulb were also
      discussed. RESULT: Sixty-five patients (22.6%) were diagnosed as HJB by HRCT
      scan, including 21 men and 44 women (P<0.01), with their ages ranged from 7 to 68
      years (mean 41 years). Fourteen cases of them were on the left side, and 31 were
      on the right side (P<0.05). Twenty cases showed bilateral HJB. Five cases were
      found dehiscent high jugular bulb by CT scan and were confirmed in operation.
      Active bleeding was encountered in one case while elevating the pathological
      eardrum in hypotympanum. It was treated by pressure compression using collagen
      gelfoam cushion covered by muscle to protect the dehiscent bulb. The patients
      proceed through the planned surgery without complications. CONCLUSION: HJB might
      cause hemorrhage during middle ear surgery, but preliminary attention, correct
      treatment and awareness of the pitfalls may lessen the operation risk.

PMID- 17511173
TI  - [A temporal bone CT study of the infants with hearing loss referred from
      universal newborn hearing screening].
AB  - OBJECTIVE: To explore the high resolution CT image of temporal bone in infants
      with hearing loss, and its value in evaluating the cause of hearing loss. METHOD:
      In 2005, 0.12 million newborns have been included in the hearing screening system
      in Shanghai, and 1077 infants have failed to pass the hearing screening. One
      hundred and eight four infants were diagnosed as congenital hearing loss from
      mild to profound. A temporal bone HRCT scanning was performed to these infants.
      RESULT: Among the 184 patients with congenital hearing loss, HRCT showed that 26
      cases (14.1%) were associated with external ear malformation, and 21 cases
      (11.4%) were associated with middle ear malformation, 31 cases (16.8%) associated
      with inner ear malformation. The patients with inner ear malformation included 12
      cases with Mondini malformation, 1 case with common cavity malformation, 6 cases
      with large vestibule malformation, 5 cases with internal auditory canal
      abnormalities, and 10 cases with vestibule, semicircular canals abnormalities. In
      addition, there were 20 cases (10.8%) with fluid in middle ear. CONCLUSION: HRCT
      image play an important role in the differential diagnosis and treatment of
      infants with congenital hearing loss.

PMID- 17511174
TI  - [The sensory organization in the posture stability with interruption induced by
      standing foam in normal subjects].
AB  - OBJECTIVE: To investigate the sensory organization in the postural stability
      under sensory conflict induced by standing foam surface in normal individuals.
      METHOD: One hundred and six normal subjects were tested using the computerized
      posturography under the firm surface and foam surface with eye open and eye
      closed for 30 seconds respectively. The standing foam surface was to interrupt
      the somatosensory and closing eyes was to interrupt the visual input in the
      postural stability. The sway velocity (SV) of body under different sensory
      conflict condition was recorded as parameter of postural stability and the effect
      of organization between the vestibular, visions and somatosensory was analyzed
      quantitatively. RESULT: (1) The SV decreased when the visual cue or/and
      somatosensory cue be interrupted (P<0.01); (2) The decreased degrees of SV
      induced by the change of visual cue were (12.12+/-6.1)% and (30.58+/-9.69)% when
      the somatosensory cue be interrupted or not. The decreased degrees of SV induced
      by the change of somatosensory cue were (18.31+/-6.56)% and (36.25+/-8.90)% when
      the visual cue be interrupted or not. The decreased degrees of SV induced by the
      change of both somatosensory and visual cue were (46.21+/-8.67)%; (3) The most
      important sensory input for keeping balance is vestibular cue, followed by the
      somatosensory and visual cues and the relationship among these three sensory is
      nonlinear. CONCLUSION: Through recording the postural stability quantitatively
      under different conditions of sensory conflict induced by standing foam surface
      or closing eyes, it is possible to evaluate the sensory organization of the three
      kinds of sensory input including the visual, somatosensory, and vestibular input
      in postural control. It exist the various balance strategy for keeping postural
      stability under sensory conflict in normal subjects. When one or two sensory
      input was interrupted in the static balance, the center nervous system has a
      complicated mechanism of sensory organization to keep balance even in the normal
      subject.

PMID- 17511175
TI  - [The application of microscope in operation to the patients with preauricular
      fistula].
AB  - OBJECTIVE: To evaluate the efficacy of microsurgical treatment of preauricular
      fistula (IPF). METHOD: The clinical data of 102 ears with IPF underwent
      microsurgical treatment were reviewed retrospectively. RESULT: One hundred ears
      (98.04%) recovered from the microsurgical treatment without recurrence.
      CONCLUSION: Microsurgical technique is simple, safe and valuable in treating IPF,
      particularly when it comes to the patients with post operational recurrence,
      repeated infection or too much scar tissue.

PMID- 17511176
TI  - [The curative effect of corticosteroid on acute otitis media with middle ear
      effusion].
AB  - OBJECTIVE: To investigate the curative effect of corticosteroid on acute otitis
      media (AOM) with middle ear effusion. METHOD: Forty-three children (43 ears) with
      AOM and abnormal tympanogram were enrolled in a prospective, randomized trial.
      Twenty-three cases (23 ears) were treated with Dexamethasone and Cefuroxime
      Sodium, while the other 20 cases (20 ears) were only treated with Cefuroxime
      Sodium. RESULT: The period of normalization of tympanometric findings in
      Dexamethasone treatment group was (54.6+/-6.2) days, which was much longer than
      that in the group without Dexamethasone treatment (38.5+/-6.1). Three months
      after treatment, the curative rate of Dexamethasone treatment group was higher
      than that of the group without Dexamethasone treatment. CONCLUSION:
      Corticosteroid can obviously improve middle ear effusion and shorten the duration
      of middle ear effusion of AOM in the first 2 weeks. To some extent,
      corticosteroid can also improve middle ear effusion in long term. It indicates
      that corticosteroid be used as an effective adjunctive drug in treating AOM with
      middle ear effusion.

PMID- 17511177
TI  - [Comparative study of several methods for producing experimental animal model of
      viral facial palsy].
AB  - OBJECTIVE: To select the optimal method for developing experimental animal model
      of viral facial paralysis by comparing several inoculation methods. METHOD: One
      hundred and twenty Balb/c mice were divided into 4 groups, with each group having
      30 mice. Group A, the posterior auricular branch of right facial nerve were
      incised and inoculated with 25 microl HSV-1; group B, 25 microl HSV-1 were
      inoculated into the posterior aspect of the right auricle by cutaneous
      scarification; group C, 25 microl HSV-1 were injected into subcutaneous tissue of
      the posterior aspect of the right auricle; group D, 100 microl HSV-1 were
      inoculated in the way similar to that of group C. The symmetry of mouse face was
      observed, and the incidence of paralysis and death were analyzed. The temporal
      bones of paralyzed mice were serially sectioned and stained with hematoxylin and
      eosin. RESULT: Thirteen (43.33%) mice developed the right facial paralysis and
      recovered from it 3-7 days later in group A. Six (20%) mice developed the
      paralysis and recovered from it 2-9 days later in group B. Group C had no signs
      of facial paralysis and group D had 1 paralyzed animal. Except for 12 mice in
      group D, there was no death in the other groups. Nerve swelling was observed in
      right temporal facial nerve of paralyzed mice. Facial nerve to facial canal cross
      sectional area ratio (FN/FC) of the right side was much higher than that of the
      left side. CONCLUSION: Inoculating HSV-1 into the posterior auricular branch of
      facial nerve can produce an acute and transient facial paralysis in mice. With
      the advantage of higher morbidity of facial paralysis and lower mortality in
      comparison to the other methods, it is an optimal method.

PMID- 17511178
TI  - [Culture, identification and label of embryonic rat neural stem cells].
AB  - OBJECTIVE: To explore the methods of culture, identification and label of
      embryonic rat neural stem cells. METHOD: The cells isolated from fetal rat
      hippocampus were identified with nestin immunocytochemical fluorescent staining.
      The cellular multiplication was observed by immunocytochemical fluorescence co
      label after accession of BrDU. The neural stem cells (NSCs) were marked with
      fluorescent dye, bisbenzimide (Hoechest33342) and induced to differentiate. The
      differentiated cells were detected with Neuron Specific Enolase (NSE) and Glial
      Fibrillary Acidic Protein (GFAP) immunocytochemical fluorescent staining
      respectively. RESULT: Nest-like clusters of neural stem cells were obtained in
      suspension and the cells could be differentiated into neurons and astrocytes
      which maintaining the main characteristics of NSCs after 8 passages of culture.
      The label efficiency of cells with Hoechest33342 was 97% and no attenuation of
      fluorescent brightness was observed after 8 passages of culture. The cellular
      fluorescence was observed in the NSCs and the differentiated cells. CONCLUSION:
      The cells from embryonic rat hippocampus possessed the abilities of division,
      multiplication and self-renew, which were believed to be the main characteristics
      of NSCs of the central nervous system. The cells could be efficiently labeled
      with fluorescent dye and could be used as donor cells in experimental research on
      NSCs transplantation.

PMID- 17511179
TI  - Persistant dysphonia following endotracheal intubation.
AB  - Voice production is a complex process that involves more than one system, yet
      most causes of dysphonia are attributed to disturbances in the laryngeal
      structures and little attention is paid to extralaryngeal factors. Persistent
      dysphonia after general anesthesia is a challenge to both anesthesiologists and
      otolaryngologists. The etiology is often multivariable and necessitates a team
      approach for proper diagnosis. Laryngeal symptoms are subdivided into phonatory
      disturbances and airway related complaints. When they become persistent for more
      than 72 hours or are coupled with airway symptoms such as hemoptysis, stridor,
      dyspnea or aspiration, the anesthesiologist should suspect injury to the vocal
      folds or cricoarytenoid joints. Here-below, the laryngeal manifestations of
      endotracheal intubation and the pathophysiology of vocal fold scarring are
      discussed.

PMID- 17511180
TI  - Management of the patient at high risk for postoperative nausea and vomiting.
AB  - Postoperative nausea and vomiting continue to be problematic areas in anesthesia
      as evidenced by frequent reports of therapies in the literature. No single
      therapy has been proven curative for all cases, in part because of the several
      emetic centers, all of which may be blocked by different classes of drugs and the
      diverse risk factors which act alone or in combination to cause vomiting.
      Identification of the patient most at risk allows for cost effective prophylactic
      management. An appropriate anesthetic technique can be planned that, relying on
      evidence based medicine, will decrease if not prevent the incidence of this most
      troubling complication.

PMID- 17511181
TI  - The safety of percutaneous tracheostomy in patients with coagulopathy or
      thrombocytopenia.
AB  - The safety and complications of percutaneous tracheostomy (PT) without
      bronchoscopic guidance in a group of ICU patients with thrombocytopenia platelet
      count of < or = 60.000/mm3) or coagulopathy (INR > or = 1.5 or systemic
      heparinization), was studied. During the study period (May 2004-June 2005), 190
      percutaneous tracheostomies were performed. Of these there were 11 (6%) patients
      with prolonged INR, 7 (4%) patients with thrombocytopenia and 14 (7%) patients on
      systemic heparin. There was no evidence of bleeding in patients with prolonged
      INR. A minor bleeding developed in only one patient with thrombocytopenia, and in
      two patients receiving systemic heparin. The PT was aborted for one patient with
      thrombocytopenia and slight increase of INR (1.3) due to major bleeding in spite
      of transfusion of both platelets and FFP. Our data suggest the incidence of
      bleeding is low in patients with coagulopathy and or thrombocytopenia-undergoing
      PT without bronchoscopic guidance.

PMID- 17511182
TI  - Hemodynamic profile during laparoscopic cholecystectomy versus laparoscopic
      bariatric surgery: the impact of morbid obesity.
AB  - The present study investigated the hemodynamic profile using impedance
      cardiography (ICG) monitor during pneumoperitoneum for laparoscopic
      cholecystectomy versus bariatric surgery in order to determine the impact of body
      weight on hemodynamics. METHODS. 32 adult patients (two groups, each 16 patients)
      were studied. Group 1 (16 patients) scheduled to undergo laparoscopic
      cholecystectomy (lapchole) with body mass index (BMI) 28 +/- 5 kg/m2. Group 2 (16
      patients) scheduled to undergo laparoscopic adjustable band (LAGB) surgery for
      treatment of morbid obesity with BMI 45.3 +/- 8 kg/m2. under general anesthesia.
      Besides routine monitoring, impedance cardiography was used for hemodynamic
      monitoring. Three stages were identified for statistical analysis A, pre
      insufflation, B, during vere pneumoperitoneum and C, at gas deflation. RESULTS.
      The mean values of cardiac index in group 1 at stages A, B and C were, 3.0 +/-
      1.7, 2.5 +/- 0.5 and 2.7 +/- 0.5 L/min/m2 respectively with significant low
      values in stage B compared to stage A (p < 0.05). The same trend continue in
      group 2 where the mean values were, 2.4 +/- 0.6, 1.8 +/- 0.6 and 2.3 +/- 0.9
      L/min/m2 respectively with significant differences compared to group 1 mean
      values (p < 0.05). Other hemodynamic variables showed non-significant differences
      (p > 0.05). CONCLUSIONS. Cardiac index showed significant decreasing trend in
      morbid obese patients compared to nonobese, which may reflect the effect of body
      weight on hemodynamics. On the other hand other hemodynamic parameters was not
      altered by body weight. We believe that hemodynamics should be closely monitored
      during laparoscopic surgery with pneumoperitoneum.

PMID- 17511183
TI  - Effect of pneumoperitoneum on the level of plasma potassium.
AB  - The purpose of this study was to find out the impact of acute respiratory
      acidosis on serum potassium level during laparoscopy. The study was performed on
      ninety patients who underwent laparoscopic surgery. Ventilation parameters were
      kept constant throughout the study. Samples for assessment of blood gases were
      collected in the following sequence: before pneumoperitoneum, a the 20th minute
      of pneumoperitoneum, at the 60th minute of pneumoperitoneum, and after
      extubation. The systolic, diastolic pressures and heart rate were recorded
      simultaneously. Before pneumoperitoneum, heart rate, systolic and diastolic
      pressures were reduced according to baseline values. With the induction of
      pneumoperitoneum, both systolic and diastolic pressures returned to the baseline
      levels except the heart rate. There was a statistically significant increase in
      potassium level (Control: 3.49 mEq.L(-1), determined high level: 3.75 mEq.L(-1)).
      Electrolytes, especially potassium, should be monitored during laparoscopy
      utilizing CO2 pneumoperitoneum and when necessary, ventilatory parameters should
      be adjusted.

PMID- 17511184
TI  - Septic shock: review and anesthetic considerations.
AB  - Sepsis and shock are severe conditions that, when together, may cause multiple
      organ failure. The anesthesiologist must be able to take a careful history and
      physical, as well as be aware that additional tests are necessary to assess the
      patient status, as preoperative systemic blood pressure is not indicative of
      adequate volume status. In preparation for surgery, one must anticipate
      dysfunction and have adequate blood products and antibiotic at hand. Ketamine is
      notable for induction in these patients because it is less likely to decrease
      systemic vascular resistance too quickly. One must not take this lightly, as
      death may ensue if proper management is not taken.

PMID- 17511185
TI  - Combined spinal-epidural analgesia in labor--comparison of sufentanil vs
      tramadol.
AB  - BACKGROUND: Combined spinal-epidural (CSE) analgesia is becoming increasingly
      used to provide pain relief during labor. It combines both the rapid onset of the
      spinal analgesia and the flexibility of the epidural catheter. Intrathecal
      sufentanil provides rapid-onset and profound analgesia during the first stage of
      labor. The dose required to produce this effect can be associated with maternal
      respiratory depression, hypotension, nausea, or pruritus. The major concern of
      the anesthesiologist is to limit these side effects sources of discomfort to a
      parturient, by choosing the optimal dose of sufentanil or searching for an
      alternative. The purpose of this study is to compare tramadol and sufentanil used
      in CSE analgesia in terms of duration of analgesia and frequency of adverse
      maternal or fetal effects. METHODS: Forty parturients requesting labor analgesia
      were included in this prospective study. In a combined spinal- epidural
      technique, at 3 to 4 cm cervical dilation, patients were randomly assigned to
      receive either one of the following intrathecal solutions: 2.5 mg sufentanil (n =
      20) and 2.5 mg bupivacaine, or 25 mg tramadol (n = 20) and 2.5 mg bupivacaine.
      Visual analog scores for pain, blood pressure, heart rate, sensory levels,
      incidence of nausea and pruritus, motor blockade, and maternal satisfaction, were
      recorded. RESULTS: Patients receiving 25 mg intrathecal tramadol with 2.5 mg
      bupivacaine had significantly longer-lasting analgesia (114 +/- 7 min). than
      those receiving 2.5 mg intrathecal sufentanil and 2.5 mg bupivacaine (54 +/- 11
      min). No adverse maternal or fetal effects were noted in the group sufentanil.
      Five parturients of the tramadol group, presented vomiting 10 min after
      induction. There was no difference in the time from analgesia to delivery,
      incidence of operative or assisted delivery or cervical dilation. During labor,
      maternal satisfaction was good. CONCLUSIONS: 2.5 micrograms of intrathecal
      sufentanil combined with 2.5 mg bupivacaine provides rapid-onset and profound
      analgesia during the first stage of labor without adverse maternal or fetal
      effects. 25 mg intrathecal tramadol with 2.5 mg bupivacaine had longer-lasting
      analgesia. The major side effect was vomiting.

PMID- 17511186
TI  - Combined regional-general anesthesia: evaluation of remifentanil based general
      anesthesia and postoperative epidural analgesia.
AB  - OBJECTIVES: To evaluate whether remifentanil based general anesthesia combined
      with epidural analgesia for postoperative pain, has any advantages with respect
      to consumption of drugs, blood loss, quality of pain control, hemodynamic
      profile, in major abdominal surgery, as compared to other combined techniques.
      METHODS: A retrospective study based on chart reviews of patients who have
      undergone colectomy, radical cystectomy and radical prostatectomy over one year
      period in our Institution, operated under combined regional-general anesthesia.
      Twenty-six patients were analyzed and were divided into three groups according to
      the type of anesthesia received. Group A: combined general-epidural for per
      operative and postoperative pain (10 patients). Group B: combined spinal-general
      anesthesia (8 patients) post-operative analgesia consisted of parenteral
      mepiridine and paracetamol. Group C: remifentanil based general anesthesia
      followed by epidural for postoperative analgesia (8 patients). RESULTS: The
      demographic data, age and M/F distribution were comparable in the three groups.
      The remifentanil group showed less utilization of muscle relaxant (Cisatracurium)
      with respect to other groups (p < 0.001). The amount of intraoperative blood loss
      was not significantly different among the three groups. The efficacy of the
      postoperative epidural analgesia was demonstrated by the minimal utilization of
      analgesics (p < 0.05 and 0.01) in group A and C as compared to group B. In the
      group of remifentanil, the blood pressure was more stable and maintained at a
      systolic of 80-100 mmHg as compared to initial hypotension mainly in group C.
      CONCLUSION: The use of remifentanil based general anesthesia offers the advantage
      of non-accumulation of drugs and hemodynamic stability. Post-operative analgesia
      can be provided by epidural route which proved to be satisfactory in the
      remifentanil group. The effect on blood loss was not conclusive in this study.

PMID- 17511187
TI  - Post-thoracotomy analgesia--comparison epidural fentanyl to intravenous
      pethidine.
AB  - BACKGROUND AND METHODS: To evaluate the efficacy of postthoracotomy analgesia
      with intermittent epidural fentanyl. 50 patients were allocated randomly into 2
      groups. The first group received intermittent epidural fentanyl and the second
      group received intermittent intravenous analgesia using pethidine. The variables
      studied were: pain score; total amount of additional intravenous opioid
      analgesia, and ventilatory function parameters [forced vital capacity (FVC),
      forced expiratory volume in the first second (FEV1) and FEV1/FVC ratio]: RESULTS:
      In the first postoperative day, pain scores were higher in the epidural group (P
      = 0.034), but there was no significant difference between mean pain scores in the
      second and third days (P = 0.61, P = 0.15, respectively). On all three days,
      significantly more additional analgesics were required in the epidural group. A
      difference was found between both groups in the post- to pre-operative FEV1, FVC
      and FEV1/FVC ratios, with the better preservation of the ventilatory function in
      the epidural group (P = 0.001, 0.013, <0.0001, respectively). CONCLUSION: The
      analgesic effect of intermittent epidural fentanyl is not adequate and
      postoperative pain relief has not any significant advantage over the more easily
      applied intravenous analgesia. However, better preservation of ventilatory
      function makes epidural fentanyl a useful adjunct analgesia in reduction of post
      thoracotomy pulmonary complications.

PMID- 17511188
TI  - Esophageal temperature monitoring.

PMID- 17511189
TI  - Factors influencing the choice of anesthesia as a career in a developing country.
AB  - Career choice in medicine is influenced by several factors. Our aim was to look
      at reasons for choice of anesthesia as a career in a cohort of doctors applying
      for the residency training in a university hospital in a developing country. A
      semi-structured interview form is used in our department and includes a question
      related to career choice. Each applicant is interviewed by two faculty members
      independently. All interview forms between 1992 to 2004 were reviewed and the
      reason for choosing anesthesia was coded in different categories. The sample
      consisted of 167 applicants and 334 forms. There were 29 females and 138 males.
      The mean age of the applicants was 28 years. Sixty two percent chose anesthesia
      because of general interest and nature of the specialty, 24% of these mentioned
      had no specific reasons, 17% thought the specialty was intellectually
      challenging, 8% liked the technical aspect, 5% were interested in physiology and
      pharmacology, 2% liked the operating room environment, and 6% liked the immediate
      results. The second major group (36%) cited the reason as better economic
      opportunities. Sixteen percent were influenced by friends or relatives in their
      choice. Twenty six percent chose anesthesia primarily because of their interest
      in critical care, pain management or emergency management. Our data indicates
      that selection of career in anesthesia in our county is strongly related to the
      nature of specialty and future employment opportunities. A significant number
      were influenced by family and friends. This pattern is different from that
      reported from Australia and United States.

PMID- 17511190
TI  - Anesthetic deaths in a developing country.
AB  - It is important to ascertain the contribution of anesthesia to perioperative
      mortality in order to enable improvement in the safety and quality of care.
      Scanty literature regarding anesthetic mortality from developing countries is
      available. We present data regarding anesthesia related mortality in a university
      hospital in a developing country. We reviewed all patient deaths occurring
      between 1992-2003 occurring within 24 hours of anesthesia, as part of
      departmental quality assurance activity. The aim of study was to identify any
      contributing factors associated with mortality, and to compare our data with
      similar studies from developed and developing countries. 111,289 cases were
      handled in this period. Within 24 hours the crude mortality was 35 (3.14:
      10,000). 3 patients died at induction, 13 intraoperatively and one at emergence.
      In the postoperative period 18 (51%) cases of mortality occurred. In 4 (11%)
      cases anesthesia was found to be solely responsible (0.35 per 10,000), in 8 (23%)
      cases anesthesia was found to be partially responsible (0.7 per 10,000). In 23
      patient disease and surgical factors played a primary role. In 10 (28.5%) cases
      deaths were considered to be avoidable. Two time periods were also compared.
      Between 1992-1998 anesthesia mortality was 0.68: 10,000 anesthetics, and from
      1999-2003 it was 0.18: 10,000 Higher mortality was observed with advancing age,
      higher ASA status, emergency and complex surgical procedures. Human factor, human
      error, inadequate preoperative preparation, inappropriate postoperative care and
      lack of supervision were identified as preventable factors.

PMID- 17511191
TI  - Women emerge from general anesthesia faster than men.
AB  - Interest in the speed with which patients recover post operatively, the type of
      deficits that anesthesia may induce in them and the overall profile of their
      physiologic and psychological states, has grown rapidly over the last two
      decades. Recovery from general anesthesia is dependent on factors governing drug
      sensitivity and drug disposition. In our study of 60 males and 60 females we have
      tried to find out if there is any significant difference in males and females, in
      their emergence from the effects of general anesthesia. This was a double blind
      study carried out in hundred and twenty patients, aged 18-70 years scheduled to
      undergo elective general surgical procedures. Patient recovery was observed
      continuously after the termination of anesthesia. Timings of initial wake up
      events were recorded by the anesthesiologist who was blinded to this study. The
      time from discontinuation of anesthesia to eye opening was 6.87 +/- 2.54 min (P <
      0.001; t test) for women versus 8.78 +/- 2.66 min in men; time to respond to
      verbal command was 7.53 +/- 2.05 and 9.61 +/- 2.14 min in women and men,
      respectively (P < 0.001; t test). Considering the multitude of factors that may
      influence recovery, the gender effect appears to be a strong one. The difference
      could probably be explained by differences in physiology, enzyme activity etc.
      Investigators have noted that normal differences account for changes in function
      of the GABA receptor known to be important in the action of many anesthetics.

PMID- 17511192
TI  - Post-operative symptoms at home in children following day case surgery.
AB  - BACKGROUND: This prospective questionnaire-based study examined the post
      operative symptoms encountered by children who had day case surgery at a
      dedicated day case surgery unit. The study evaluated the postoperative symptoms
      at home. The parents also evaluated the instructions given in the hospital for
      care at home. METHODS: All children aged 1 day - 14 years operated over a one
      year period were prospectively followed up following elective day case surgery.
      The incidence and duration of symptoms were evaluated using a structured
      questionnaire completed by the parents. Also, the instructions given in hospital
      for care at home were evaluated by the parents using another questionnaire.
      RESULTS: A total of 100 children were operated during the period. Pain (72%),
      emetic symptoms (16%) and difficulty with walking (7%) were the commonest
      symptoms occurring on the way home. There were no unplanned admissions. Two
      thirds of the parents did not know enough of the treatment of the wound and of
      the overall recovery of the child. CONCLUSION: Post operative symptoms following
      elective day case surgery are amenable to treatment and prevention with a wider
      use of available drugs for peri-operative analgesia.

PMID- 17511193
TI  - The effect of betamethasone gel in reducing sore throat, cough, and hoarseness
      after laryngo-tracheal intubation.
AB  - BACKGROUND AND AIMS: Tracheal intubation for general anesthesia often leads to
      traumatization of the airway mucosa resulting in postoperative sore throat,
      hoarseness and cough. This study was undertaken to determine the effects of
      betamethasone gel in reducing these complications. MATERIALS AND METHODS: One
      hundred patients (ASA I-II) to undergo endotracheal intubation, were randomly
      divided equally into two groups; 50 Case (Group A). 50 Control (Group B). The
      tracheal tubes for Case Group A were lubricated with 0.05% betamethasone gel and
      for the Control Group B with KY gel. Patients were interviewed at end of
      procedures and 1 and 24 hour after extubation. RESULTS: The incidence and
      severity of sore throat, hoarseness and cough, 1 and 24 hours postoperatively was
      reduced significantly in Case Group A. CONCLUSION: Betamethasone gel, when was
      used for lubrication of endotracheal tubes pre-operatively, was shown to be
      effective in decreasing postoperative sore throat, hoarseness, and cough.

PMID- 17511194
TI  - Recovery profile for magnetic resonance imaging in pediatric daycase--sevoflurane
      vs. isoflurane.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is gaining ground over other
      investigations particular in study of brain and soft tissues. The MRI procedure
      is painless but requires an immobile patient for a successful study. Children are
      required to be sedated or anesthetized for this procedure. We compared two
      inhalational anesthetics, namely sevoflurane and isoflurane, for the recovery
      profile of each with aim to determine the ideal drug for early discharge of
      children. PATIENT AND METHODS: 100 patients aged 3 yrs to 10 yrs (ASA I and II)
      were divided into Group S (Sevoflurane), Group I (Isoflurane). The induction
      time, duration of the MRI study, recovery and discharge times were recorded. The
      data were subjected to Students t-test and Levene's test for equal variance.
      RESULTS: In Group S, 27 male and 23 female were enrolled in comparison to 30 male
      and 20 female in Group 1. The induction time in Group S resulted in a mean of
      133.7 seconds +/- 19.32), Group I yielded a mean of 157.44 seconds (+/- 24.20) p
      > 0.05). The mean recovery time with Group S was 124.4 seconds (+/- 31.57) when
      compared with Group I a mean of 376.46 seconds (+/- 58.20) p < 0.05. The mean
      discharge time in Group S was 25.20 minutes (+/- 5.71) in comparison to a mean of
      37.40 minutes (+/- 7.43) p < 0.05 in Group I. CONCLUSION: Sevoflurane can be an
      ideal inhalational anesthetic for Volatile Induction and Maintenance Anesthesia
      (VIMA) in children under going daycase MRI examinations.

PMID- 17511195
TI  - Myasthenia gravis and sevoflurane--a case report.
AB  - Myasthenia gravis is characterized by weakness and easy fatiguability of
      voluntary muscles. Myasthenic patients are sensitive to non-depolarizing
      relaxants. Sevoflurane, as an alternative, can be used to achieve good tracheal
      intubation. In this report, we present our experiences.

PMID- 17511196
TI  - Anesthesia for thoracoscopic thymectomy: modified non-muscle relaxant technique-
      case reports.
AB  - Anesthesia for thymectomy in myasthenia gravis is challenging. The anesthetic
      experience of that technique is quite large. In involves either muscle relaxant
      or non-muscle relaxant techniques. However, the literature is deficient of
      standard anesthetic technique for thoracoscopic thymectomy. Therefore we present
      in this report a modified non-muscle relaxant technique for thoracoscopic
      thymectomy (TT). We report two cases who underwent TT under general anesthesia
      using sufentanil and propofol for induction and local anesthesia spray to the
      vocal cords to facilitate endobronchial intubation using non-muscle relaxant
      technique. The intubating, operating and postoperative conditions were excellent.
      To the best of our knowledge, this is the first report on modified non-muscle
      relaxant technique for TT in myasthenia gravis. Further cases have to be done to
      verify our technique.

PMID- 17511197
TI  - Intraoperative bronchospasm under spinal analgesia--a case report.
AB  - The involvement of respiratory system occurs mainly as a result of a high spinal
      block. Our case describes the unusual effect of mid-spinal analgesia. We
      encountered bronchospasm in an otherwise healthy patient undergoing inguinal
      hernia repair under subarachnoid block. The highest level of block was T6. The
      anxiety of the patient further aggravated the symptoms. This is probably the
      first reported incident of bronchospasm as a result of spinal anesthesia. We
      speculate the role of unblocked parasympathetic system in the causation of this
      respiratory complication.

PMID- 17511198
TI  - Anesthetic management of iatrogenic esophageal perforation--case report and
      literature review.
AB  - The incidence of esophageal perforation may be increasing as endoscopic
      procedures are becoming a standard diagnostic technique. Other situations such as
      vomiting, infection, malignancies may also be associated with esophageal rupture.
      Presenting symptoms may be non specific but delay in accurate diagnosis carries a
      high morbidity and mortality. Anesthetic management is critical to survival. A
      case of esophageal rupture and its management is presented along with a
      literature review.

PMID- 17511199
TI  - Anesthetic management of dilated cardiomyopathy--a case report.
AB  - We report the anesthetic management of a patient with dilated cardiomyopathy,
      scheduled for surgery for fracture of femur. The risks involved and the potential
      benefit of the use of regional versus general anesthesia, are discussed.

PMID- 17511200
TI  - Creating positive practice environments.

PMID- 17511201
TI  - Nurses challenge editorial.

PMID- 17511202
TI  - NZNO berated for fee increase.

PMID- 17511203
TI  - How midwives can get client feedback.

PMID- 17511204
TI  - Turning a nursing vision into a working reality.

PMID- 17511205
TI  - Changing unhealthy work environments.

PMID- 17511206
TI  - Silence kills--challenging unsafe practice.

PMID- 17511207
TI  - Corporate bullying--a virulent organism.

PMID- 17511208
TI  - Creating new workplace culture.

PMID- 17511209
TI  - Self care is an important role for nurses.

PMID- 17511210
TI  - Strengthening health services.

PMID- 17511211
TI  - How do nurses care for prisoner patients?

PMID- 17511212
TI  - Do we have safe and healthy workplaces yet?

PMID- 17511213
TI  - [Endoscopic findings in GERD and NERD].

PMID- 17511214
TI  - [Definition and classification of GERD].
AB  - Gastro-esophageal reflux disease(GERD) is a condition which develops when the
      reflux of stomach contents causes troublesome symptoms and/or complications.
      Traditionally, it was defined as a condition in which either or both of reflux
      esophagitis and reflux symptoms can be identified. The Montreal definition
      expanded the category of GERD to complications of esophagitis and extra
      esophageal symptoms with or without established evidence on the correlation with
      GERD. Symptomatic patients those who lacks the evidence of mucosal breaks are
      called as NERD. Functional heartburn, defined in Rome III, is similar in symptoms
      but different in the responsiveness to PPIs. Increasing knowledge will clarify
      what the gastroesophageal reflux really causes health problems.

PMID- 17511215
TI  - [Epidemiology of GERD in Japan].
AB  - To determine the epidemiological characteristics of Japanese patients with
      gastroesophageal reflux disease(GERD), we investigated the prevalences of
      heartburn, reflux esophagitis(RE), hiatus hernia and Barrett's mucosa, and
      assessed the correlations among them. In total, 15.4 % (725/4,723) of patients
      had heartburn twice or more per week and 42.2% had symptoms of heartburn,
      including those who had heartburn once or less per week, and 16.7 % (602/3,608)
      of patients had RE. The prevalences of hiatus hernia and Barrett' s mucosa were
      49.3 % (1,263/2,560) and 20.8% (536/2,577), respectively. There was a weak
      correlation between RE and heartburn, but 75.5% of patients who had heartburn did
      not have any endoscopic abnormalities, and 40.1% of patients without endoscopic
      abnormalities had heartburn, suggesting the presence of endoscopy-negative GERD.
      Results also showed that 26.2 % of patients had RE associated with hiatus hernia,
      and there was a correlation between the two. There was a weak correlation between
      Barrett' s mucosa and RE and between Barrett' s mucosa and hiatus hernia.

PMID- 17511216
TI  - [Pathogenesis of gastro-esophageal reflux disease].
AB  - Gastro-esophageal reflux disease (GERD) refers a condition that develops when the
      reflux of stomach contents causes troublesome symptoms and/or complications. The
      disease was subclassified into esophageal and extraesophageal syndromes in the
      new Montreal Definition. Hiatal hernia, decreased lower esophageal sphincter,
      transient lower esophageal sphincter relaxation, esophageal acid clearance, and
      delayed gastric emptying might be implicated as the pathogenesis of esophageal
      syndrome. Although non-erosive reflux disease (NERD) is included in the
      esophageal syndrome, it might be different from reflux esophagitis because of the
      lower response rates to acid suppression with proton pump inhibitors. Esophageal
      visceral hypersensitivity, sustained esophageal contractions, and abnormal tissue
      resistance are thought to be the mechanisms of NERD. Further investigations for
      the pathogenesis of each classification are expected.

PMID- 17511217
TI  - [Immunohistochemical analysis of cell cycle-regulating protein (p21, p27 and
      Ki67) expression in endoscopic biopsy samples from patients with gastroesophageal
      reflux disease].
AB  - We performed an immunohistochemical analysis of cell cycle-regulating protein
      (p21, p27 and Ki67) expression in endoscopic biopsy samples from the patients
      with gastroesophageal reflux disease (GERD) using angled -biopsy forceps.
      Inflammatory cell accumulation into the lamina propria was detected even in
      patients with modified Los Angeles (LA) system grades N or M. In grade N or M
      patients with no changes in the epithelium, the area of p21, p27 and Ki67
      positive cells was expanded compared to normal mucosa. The area of p21, p27 and
      Ki67 positive cells tended to expand upward in the epithelium with GERD severity
      based on the LA classification grading. These indicate that inflammatory cell
      infiltration into the lamina propria is initial histological change of GERD.

PMID- 17511218
TI  - [Cytokine expression in GERD].
AB  - The mechanism of esophageal mucosal injury has gradually been understood at the
      microbiological level. It is particularly important that pro-inflammatory
      factors, such as inflammatory cytokines, leukocytes and oxidative stress, have
      been demonstrated to be involved in the development of gastroesophageal reflux
      disease (GERD) including nonerosive reflux disease (NERD). Our present study
      reveals that expression of IL-8 mRNA, a potent neutrophil chemotactic and
      activating peptide, is correlated with the endoscopic grade of esophagitis or
      with inflammatory cell infiltration. In addition, it has been shown that bile
      acids and trypsin can promote IL-8 production from human esophageal epithelial
      cells via NFkappaB-and AP-1-dependent mechanism. Nociceptors such as acid
      sensitive vanilloid receptors, protease-activated receptors and neuropeptides
      such as substance P have also been implicated in the pathogenesis of neurogenic
      inflammation in NERD patients with esophageal hypersensitivity. The development
      of new therapy with antiinflammatory and anti-oxidant effects is expected to
      assist in the treatment of intractable NERD/GERD and the prevention of
      carcinogenesis.

PMID- 17511219
TI  - [Pathogenesis of GERD--peculiarity of NERD].
AB  - Gastroesophageal reflux disease can be divided into two groups, reflux
      esophagitis and non-erosive reflux disease, according to the presence of
      esophageal mucosal breaks. Almost all the reflux esophagitis with mucosal breaks
      are caused by the pathological reflux of acidic gastric contents to esophagus.
      Therefore, drugs that suppress gastric acid secretion effectively control reflux
      symptoms. On the other hand, almost 40% of nonerosive reflux disease are not
      caused by the reflux of gastric acid but by acid-unrelated mechanisms. Therefore,
      administration of proton pump inhibitors cures reflux symptom of only 50% of
      cases with non-erosive reflux diseases. The multi-pathogenesis of nonerosive
      reflux disease should be considered for the treatment of patients with reflux
      symptoms.

PMID- 17511220
TI  - [Pathophysiology of gastroesophageal reflux disease: motility factors].
AB  - Reflux esophagitis (RE) is characterized by excessive esophageal acid exposure.
      The number of acid reflux episodes, the way acid comes up after reflux and the
      delay of acid bolus clearance cause excessive esophageal acid exposure. Transient
      lower esophageal sphincter relaxation(TLESR) is the major mechanism of acid
      reflux in both healthy subjects (HS) and in patients with acid reflux disease,
      but there is no difference in the rate of TLESRs or in the rate of acid reflux
      during TLESRs above the LES between HS and patients with severe RE. In patients
      with severe RE, refluxed acid above the LES rises more easily to the proximal
      esophagus but it does not clear easily from the esophagus when compared with HS.
      The pathophysiology of non-erosive reflux disease (NERD) is poorly understood,
      however with regard to esophageal motility in patients with NERD, the LES
      pressure, the pressure wave amplitude and the rates of successful primary
      peristalsis were similar to that of HS but the triggering of secondary
      peristalsis was defective. This may lead to prolonged contact time between
      refluxed gastric acid and esophageal mucosa thereby leading to symptoms.

PMID- 17511221
TI  - [Relationship between gastric motility and the pathophysiology of GERD].
AB  - Various factors contribute to the reflux symptoms such as heartburn and
      regurgitation in patients with GERD. There have been some reports on delayed
      gastric emptying or impaired gastric myoelectrical activity in those with GERD.
      The reason for the direct relationship between reflux symptoms and gastric
      hypomotility in GERD patients is still unclear. Gastric distension and impaired
      fundic relaxation as a result of disturbed gastric motility might play a partial
      role in acid reflux to the esophagus. Gastric hypomotility appears to be an
      important causative factor in the reflux symptoms in some GERD patients.

PMID- 17511222
TI  - [Helicobacter pylori infection and GERD].
AB  - Helicobacter pylori (H. pylori) is an important pathogen that is known to be
      associated with gastritis, peptic ulcer diseases, and gastric cancer. The
      association between H. pylori infection and gastro-esophageal reflux disease
      (GERD) is, however, uncertain. Recent studies indicate that the prevalence of H.
      pylori is significantly lower in patient with GERD from East Asia than in
      patients from Western Europe and North America, and that H. pylori might protect
      against GERD. The frequency of hypochlorhydria might due to atrophic gastritis
      induced by H. pylori infection is associated with the low prevalence of GERD in
      Japan.

PMID- 17511223
TI  - [Questionnaires for GERD, QUEST and F scale].
AB  - The initial diagnosis of GERD is based on the history or on questionnaires such
      as QUEST and FSSG(F scale): frequency scale for the symptoms of GERD. A higher
      QUEST score only signifies that an event is more typical of gastroesophageal
      reflux than of other conditions, so changes in the score for QUEST cannot be used
      to assess the severity of GERD or the response to treatment. We developed a
      simplified questionnaire, F scale, for evaluation of the symptoms of GERD. The
      results of F scale correlated strongly with the endoscopic findings, therefore,
      use of F scale would allow objective assessment of the therapeutic effect of
      various PPIs, including on demand therapy.

PMID- 17511224
TI  - [PPI-test].
AB  - GERD (gastro esophageal reflux disease) is defined as a condition that develops
      when the reflux of stomach contents causes troublesome symptoms and/or
      complications. Endoscopic-positive GERD can be easily diagnosed with endoscopy,
      while endoscopic-negative GERD cannot be. PPI test, which reveals the disorders
      by judging symptom-relief after PPI administration, is an effective tool for
      diagnosis of NERD, and extraesophageal GERD such as LPRD and bronchial asthma.
      Diagnostic power of PPI test is limited owing to the low PPI's cure rate against
      NERD, about 40%. PPI test-negative NERD is considered as non-acid associated
      NERD. Most of the NERD patients have the symptoms of functional dyspepsia(FD) for
      which the most effective medication is PPI administration, leading to the notion
      that subgroup of GERD and FD is considered as an acid associated disorder. This
      diagnostic entity is practical in a sense that anti-acid treatment is very
      effective for this disease. Besides, PPI test is a very useful tool to
      differentiate acid associated disorder from GERD and/or FD.

PMID- 17511225
TI  - [Endoscopic examination including magnifying endoscopy for diagnosis of GERD].
AB  - Symptoms of heartburn and regurgitation are the most important for diagnosis of
      gastroesophageal reflux disease (GERD) in the clinical field. Endoscopic
      examination is also widely used modality for Los Angeles classification of GERD
      according to endoscopic severity of esophageal mucosal breaks. However, about
      half of GERD patients reveal no abnormality under conventional endoscopy. These
      endoscopic negative GERD is called as non-erosive reflux disease (NERD). There is
      the possibility to underestimate a minute mucosal change of GERD by conventional
      endoscopy that has the limitation of visual ability. Magnifying endoscopic
      examination is able to get clear visualization of intrapapillary capillary
      loops(IPCL), which are usually shown as dot-like structures in esophageal mucosa
      by a conventional endoscopy. The changing of IPCLs is associated with
      inflammation and neoplasia of esophagus. Minute change of IPCLs such as a
      dilation and elongation with regular intervals were reported to be suggestive of
      inflammatory change in esophagus. Magnifying endoscopic observation of IPCLs is
      useful for diagnosis of NERD which cannot be visualized by conventional
      endoscopy.

PMID- 17511226
TI  - [Histopathological diagnosis in gastroesophageal reflux disease].
AB  - We reviewed the histopathological features for the diagnosis of gastroesophageal
      reflux disease (GERD). The presence of infiltration inflammatory cells, thickened
      basal cell layer, increased papillary height was histopathologically evaluated in
      GERD patients. It is often difficult to diagnose GERD symptoms when there were
      few endoscopic findings, such as lack of hiatal hernia and erosive esophagitis.
      At that time, we might be able to diagnose GERD by the histopathological
      examination except the pH monitor was performed. We showed that the
      histopathological esophagitis correlated with reflux symptoms and
      laryngopharyngeal symptoms. These indicated that the histopathological
      esophagitis may be diagnosed as not only typical GERD but also atypical GERD.

PMID- 17511227
TI  - [Esophageal pH monitoring].
AB  - According to westernization of dairy life-style and aging, gastroesophageal
      reflux disease (GERD) with its physical symptoms such as heartburn is increasing
      in Japan. Although typical GERD has reflux esophagitis, GERD patients without
      abnormal endoscopic findings called non-erosive GERD (NERD) have been paid great
      attention. And more, the association between GERD and chronic respiratory
      diseases or laryngeal disease has been reported. To catch the more information
      about clinical questionnaire of GERD cases, esophageal pH monitoring is a useful
      method because of evaluating the direct condition of acid exposure of esophagus.
      Recently the new wireless pH monitoring system have been developed, this system
      is less stress than conventional method and has performance of pH recording for
      continuous 48 hours time. The widespread usage of pH monitoring system is
      expected to give us the new knowledge of GERD, NERD and GERD associated diseases.

PMID- 17511228
TI  - [Bernstein test].
AB  - It is almost 50 years ago, when L.M. Bernstein and L.A. Baker wrote a paper on
      esophageal pain created by intra-luminal acid infusion. Their main purpose was to
      distinguish the chest pain due to esophagitis from cardiac pain. As former
      experiments had failed to show the direct roll of acid on chest pain, esophageal
      pain observed in esophagitis patients had been thought to be the result of
      esophageal wall extension. Bernstein showed that acid itself could cause chest
      pains in not only endoscopically positive esophagitis patients but also in
      pseudoesophagitis patients as Bernstein called. The simple and effective method
      he developed during his trial was called as Bernstein test with respect.
      Nowadays, more than half of the patients who suffer GERD symptoms are diagnosed
      as non-erosive reflux disease (NERD). Effective management of NERD is one of the
      most anticipated fields in the clinical upper GI treatment, and for that purpose,
      selecting the group of patients who are sensitive to acid is especially
      important. In this paper, I will describe about this Bernstein's "old but up-to
      date" original paper in detail and consider its present-day interpretation. It
      has become obvious recently that acid is not the only cause of the esophageal
      pain of NERD patients. But, the importance of acid in NERD is still not small.
      Both as the theoretical basis of acid induced esophageal pain and as clinical
      method of measuring acid sensitivity in esophagus, Bernstein test should be
      recalled frequently and improved further.

PMID- 17511229
TI  - [Acid-suppressive strategy against gastroesophageal reflux diseases and non
      erosive reflux diseases: the alternative of proton- pump inhibitors or H2
      receptor antagonists].
AB  - Gastroesophageal reflux disease (GERD) is categorized into three distinct
      entities: erosive reflux diseases(ERD), non -erosive reflux diseases(NERD) and
      Barrett's esophagus. In ERD, early symptomatic relief as well as healing of the
      esophageal mucosal injury to prevent complications is the goal of the treatment,
      whereas in NERD, alleviation of the symptoms leading to better quality of life is
      the main goal. According to the results of randomized controlled trials comparing
      proton-pump inhibitors (PPIs) with H2-receptor antagonists (H2RAs) head-to-head,
      PPIs are superior to H2RAs in the treatment for ERD. However, H2RA was equally
      effective with PPI to the Japanese ERD patients with low-grade esophageal mucosal
      breaks and positive Helicobacter pylori (H. pylori) infection. PPIs are also more
      beneficial than H2RAs in NERD in Western literatures but overall therapeutic
      gains of PPIs in NERD are lower than those reported in ERD, indicating
      heterogeneity of NERD pathophysiology. Again, H2RA was reported to show equal
      effectiveness with PPI in NERD patients with positive H. pylori status in Japan.
      Thus, on -demand treatment with H2RA in NERD patients with positive H. pylori
      status could be an alternative option. In conclusion, optimal management of the
      Japanese GERD patients with acid suppressive therapies should be tailored to
      individual conditions.

PMID- 17511230
TI  - [Endoscopic therapy for gastroesophageal reflux disease].
AB  - A variety of endoscopic techniques for the treatment of gastroesophageal reflux
      disease (GERD) have been developed as alternatives to PPI therapy or antireflux
      surgery. These techniques include the delivery of radiofrequency energy to the
      gastroesophageal junction, injection of agents into the lower esophageal
      sphincter zone, and suture plication of the proximal fundic folds. Each of these
      endoscopic techniques is designed to alter the anatomy or physiology of the
      gastroesophageal junction to decrease gastroesophageal reflux. However, only
      limited data are available on the mechanism of action of the various endoscopic
      techniques. Most studies of endoscopic therapy have only limited follow-up
      information, and safety issues remain unresolved. Further sham-controlled
      clinical trials will be required for endoscopic device and technique.

PMID- 17511231
TI  - [Surgical treatment for gastroesophageal reflux disease (GERD)].
AB  - Proton pump inhibitor (PPI) is major treatment for acid reflux. It reduces major
      symptom of GERD and effective. However, the cause of GERD is the insufficiency of
      anti-reflux mechanism of cardia. Only surgical treatment can care for hiatal
      hernia as the main cause of the disruption. Redundant reflux against conservative
      treatment or obvious hiatal hernia is indication for laparoscopic Nissen
      fundoplication. Late diagnosis might request radical operation, so we need to
      know the indication for laparoscopic treatment. For the safer laparoscopic
      procedure, we perform curtain retraction technique and Floppy Nissen -short cuff
      method. The former contribute to prevent hemorrhage or pneumothorax, and the
      latter can reduce the post-operative disphagia.

PMID- 17511232
TI  - [Lifestyle modification as a medical treatment for GERD].
AB  - Lifestyles such as obesity, smoking, alcohol or fatty meal are long-time
      considered to related with the deterioration of GERD. Basic studies indicate that
      smoking and alcohol decrease LES pressure. However, the clinical studies of the
      relationship between lifestyle and GERD sometimes show coflicting results.
      Lifestyle modification as a medical treatment of GERD were reviewed.

PMID- 17511233
TI  - [Management of gastroesophageal reflux disease (GERD) with refractory to standard
      dose of proton pump inhibitor].
AB  - Approximately 10% of Japanese patients with reflux esophagitis (RE) are
      refractory to a standard dose of proton pump inhibitor(PPI) and most refractory
      patients have severe RE. Lack of response may be due to inadequate gastric acid
      suppression in conjunction with CYP2C19 genotype status and nocturnal acid
      reflux. Twice-daily dosing of PPI for inadequate gastric acid suppression and the
      administration of H2-receptor antagonist before bedtime for nocturnal acid
      reflux, is effective in most cases. The response to a standard dose of PPI in
      patients with non-erosive reflux disease (NERD) is approximately 50%. The reasons
      for a lower response rate, compared with RE patients, are not clear but may
      relate to an acid-hypersensitive esophagus, inadequate gastric acid suppression,
      non -acid reflux and emotional or psychological abnormality. High dose PPI
      therapy, endoscopic or surgical anti-reflux therapy, or/and pain modulators may
      be effective in some patients.

PMID- 17511234
TI  - [Laryngopharyngeal reflux].
AB  - Laryngopharyngeal reflux (LPR) or reflux laryngitis refers to the backflow of
      stomach contents into the larynx and hypopharynx. LPR is increasingly cited as
      the cause of laryngeal signs and symptoms such as globus sensation, hoarseness,
      chronic cough, chronic throat clearing, and throat pain. The diagnosis of LPR is
      often based on the presenting symptoms and associated laryngeal signs. An empiric
      trial of double-dose proton pump inhibitors (PPIs) has been recommended as a
      first line therapy in patients with suspected LPR. However, recent systemic
      review has shown no benefit of PPIs over placebo in the treatment of LPR.
      Clearly, more well designed, prospective large scale trials are warranted in the
      future.

PMID- 17511235
TI  - [Sleep apnea syndrome].
AB  - The association between gastroesophageal reflux disease (GERD) and obstructive
      sleep apnea syndrome (OSAS) has recently been suggested. Patients with OSAS have
      a high frequency of nocturnal GER, and patients with GERD have various sleep
      related symptom such as snoring and apnea. However, the causal relation between
      OSAS and GERD has not been sufficiently elucidated. The treatment of OSAS with
      nasal continuous positive airway pressure significantly reduces GERD symptom and
      nocturnal GER in both patients with and without OSAS. On the other hand,
      treatment of GERD in patients with OSAS improves the number of arousal during
      sleep, but one study showed a significant decline of apnea index. It is necessary
      to make further studies evaluating the association and treatment of OSAS and
      GERD.

PMID- 17511236
TI  - [Osteoporosis in elderly patients].
AB  - Recent reports indicate an increased prevalence of reflux esophagitis (RE) in
      Japan. There are many factors causing RE, and many kinds of changes associating
      aging are important in the cause of RE in elderly patients. We reported that the
      osteoporosis and the orthopedics degenerative disease in elderly people had
      relation in development of symptoms of RE of our country. The elderly are
      complicated with posture change (kyphosis) due to osteoporosis caused by
      menopause; some pharmaceutical agents such as bisphosphonates (BPs) or NSAIDs.
      Furthermore, it is necessary to provide elderly RE treatment with the all
      inclusive treatment not only the conventional medical treatment which made the
      PPI maintenance therapy but a living environment, complications, an oral medicine
      including BPs and NSAIDs.

PMID- 17511237
TI  - [Gastroesophageal reflux disease in diabetic patients].
AB  - Esophageal dysfunctions occur frequently in patients with diabetic neuropathy,
      and the complication of gastroesophageal reflux disease(GERD) has also been
      reported. However, the characteristics of GERD complicated with diabetes mellitus
      are obscure because no detailed assessment was performed. We performed long-term
      ambulatory esophageal pH and motility monitoring in diabetic patients, and
      analyzed the data in detail. Esophageal dysfunctions including GERD were
      significantly related to diabetic neuropathy and duration. Although GERD was
      frequently complicated with diabetes mellitus, the symptoms were not apparent in
      diabetic patients. The average score of a questionnaire was extremely low, and no
      significant difference in score was observed between patients with and without
      gastroesophageal reflux. We should keep in mind that diabetic patients have the
      abnormal gastroesophageal reflux even when they do not complain of the related
      symptoms.

PMID- 17511238
TI  - [Prevalence, diagnosis and treatment of extraesophageal manifestations of GERD].
AB  - Gastroesophageal reflux disease (GERD) is associated with a variety of
      extraesophageal symptoms including asthma, chronic cough, laryngeal disorders,
      and various ENT symptoms. Recent studies suggest that GERD underlies or
      contributes to chronic sinusitis, chronic otitis media, dental erosion, and
      obstructive sleep apnea syndrome (OSAS). In this article, we review the
      prevalence, diagnosis, and treatment of extraesophageal symptoms and including
      Montreal definition, a new definition and classification of GERD by an
      International Consensus Group.

PMID- 17511239
TI  - [Cost-effectiveness analysis for the treatment of non-erosive reflux disease].
AB  - Non-erosive reflux disease(NERD) is a common condition and acid-suppressing
      agents are the mainstay of treatment. A cost-effectiveness analysis comparing a
      PPI, lansoprazole (LPZ) and a H2RA, ranitidine (RAN) for the treatment of NERD in
      Japan was performed using a decision analysis. The time period studied was one
      month and payer or patient' s perspective was considered. Efficacy data were
      estimated from a randomized clinical trial. Expected days without symptom
      (healthy days) were 20 for LPZ 15 mg/day and 16 for RAN 300 mg/day. Direct costs
      were 4,750 yen for LPZ and 4,358 yen for RAN. Cost-effectiveness ratio (direct
      costs/healthy days) was 238 yen for LPZ and 272 yen for RAN. Considering the
      results from a large-scale survey of GERD patients in Japan, the slightly higher
      price of LPZ was outweighed by its greater efficacy, also from the patient's
      willingness to pay perspective. Lansoprazole was superior to ranitidine with
      regard to both efficacy and cost-effectiveness and therefore is the preferred
      therapeutic agent for treatment of NERD.

PMID- 17511240
TI  - [Loop-mediated isothermal amplification].
AB  - We have developed the loop-mediated isothermal amplification (LAMP) method, an
      innovative gene amplification technique, which has the potential to become
      important in genetic testing. This method allows highly efficient amplification
      by a single enzyme at a constant temperature. It also has features such as high
      specificity, rapidity, and simplicity of detection. Therefore, application to
      various life sciences, such as clinical medicine, is expected.

PMID- 17511241
TI  - [Influence of attentional setting and priming on the inter-trial facilitation
      effect on pop-out].
AB  - In visual search situations, it is known that not only bottom-up factors relative
      to the presented stimulus display but also top-down factors, which include
      foreknowledge about the target or observers' strategies for the task, have an
      influence on search performance. The present study examines how top-down
      attentional control settings affect the visual search process by using the within
      dimension facilitation (WDF) and the inter-trial facilitation (ITF) effects. In
      Experiment 1 we showed the WDF effect using foreknowledge about the target
      defining dimension within one block. In Experiment 2 we found the ITF effect
      using foreknowledge about the target-defining dimension in every trial. These
      results suggest that search performance is improved both top-down attentional
      setting using foreknowledge and inter-trial priming by repetition of target
      defining dimensions, and they are interactive. Furthermore, the influence of the
      priming effect strongly appeared when observers had an attentional setting every
      trial. These results show that the magnitude of bottom-up inter-trial priming
      effects depends on the top-down attentional setting.

PMID- 17511242
TI  - [The interrelationship between an anthropophobic tendency and narcissistic
      personality in adolescence].
AB  - This study investigates the interrelationship between an anthropophobic tendency
      and narcissistic personality in adolescence. Previous research has proposed that
      anthropophobia and narcissistic personality disorders can be classified into
      subtypes. In recent studies, Okano (1998) suggested that the relationship between
      an anthropophobic tendency and narcissistic personality should be explained in
      terms of two dimensions (two-dimension model), instead of one dimension (one
      dimension model). Questionnaires were administered to 305 adolescents who were
      enrolled in a university. In analysis 1, the relationship between an
      anthropophobic tendency and narcissistic personality, which are both within
      normal limits of anthropophobia and narcissism in adolescence, was examined with
      a two-dimension model. In analysis 2, the characteristics of self-consciousness
      and adaptiveness in adolescence, which were classified using a two-dimension
      model, were examined. The results were as follows: (1) an anthropophobic tendency
      and narcissistic personality could be explained with a two-dimension model; and
      (2) the characteristics of five subtypes were revealed in detail.

PMID- 17511243
TI  - [In-group bias in trusting behavior: a choice of allocator experiment with
      minimal groups].
AB  - The purpose of this study is to show that expectations of generalized reciprocity
      within one's own group are responsible for in-group trust. To test this
      hypothesis, an allocator choice game in the minimal group situation was used. We
      assigned the role of a recipient in a dictator game to all 81 subjects, and
      measured whether they chose to be a recipient of either an in-group or an out
      group "allocator" who freely allocate a fixed reward between him/her and a
      recipient. The results indicate that in-group trust occurs only in the condition
      in which recipients know that allocators make a reward allocation knowing the
      group membership of their recipient; recipients show no preference for either an
      in-group or an out-group allocator when allocators make the decision without
      knowing the group membership of their recipient. It is thus shown that
      participants' in-group trust is derived from the general belief that people treat
      in-group members more favorably than out-group members-a belief about generalized
      reciprocity within groups.

PMID- 17511244
TI  - [The congruence between the emotional valences of recalled episodes and mood
      states influences the mood congruence effect].
AB  - Many investigators suggested that self referent tasks facilitate mood congruence
      effect. Self-referential tasks are distinguished from self-descriptive tasks and
      autobiographical tasks. When using an autobiographical task, there may be
      different emotional valences of stimulus words and of recalled episodes. This
      study used an autobiographical task to investigate whether the emotional valences
      of recalled episodes influenced the mood congruence effect. Fifty-one
      undergraduate students were randomly assigned to three types of induced-mood
      groups (positive, negative and neutral). Stimuli were 40 neutral-trait-adjective
      words, presented at a rate of one word every six seconds. Participants judged
      whether they could recall any of their autobiographical memory related to the
      word, and rated the emotional valence of their recalled memory. Results suggested
      that not only the emotional valence of the stimulus but also the emotional
      valence of the recalled is important for the mood congruence effect.

PMID- 17511245
TI  - [Spatial frequency characteristics in recognizing the age and sex of faces].
AB  - The present study investigated the role of spatial frequency components in
      recognizing age and sex in facial images. In Experiment 1, low (LSF) and high
      spatial frequencies (HSF) of facial images were morphed between different age
      groups (one-year-olds, teens, twenties, and sixties), and the participants were
      required to estimate the age. The results showed that the manipulation of spatial
      frequency affected age recognition more for the faces including aged than for the
      faces including infant, suggesting that people use different cues for them. In
      addition, the recognized age was affected more by HSF components throughout.
      Recognition of sex was investigated in Experiments 2a and 2b, using the same
      faces but morphing male and female. In the judgment of sex, unlike for age
      estimation, the recognition system clearly depended on the LSF. These results
      were discussed in terms of the different roles of age and sex information and the
      development of the visual system in early infancy.

PMID- 17511246
TI  - [The influence of cognitive appraisal on the duration of negative emotional
      experience and cardiovascular response].
AB  - The duration of a negative emotional experience is associated with delayed
      cardiovascular recovery. Cognitive appraisal is thought to play an important role
      in cutting off these responses, which are related to cardiovascular disease. This
      study examined the influence of cognitive appraisal on the duration of negative
      emotional experiences and cardiovascular responses. Before a speech task,
      participants were told that their performance would be evaluated by means of a
      video camera and that they would be given the score at the end of the experiment.
      To manipulate cognitive appraisal, participants were randomly assigned to a group
      that received one of three instructions following the speech task. The "non
      threat" group was informed that there was no evaluation or feedback about the
      score; the "threat" group received that there were some obscurities in their
      speech and some questions were given while comparing with the video; the control
      group was given no instructions. After receiving their respective instructions,
      all groups were monitored for a post-task period of five minutes. The results
      showed that the "non-threat" group experienced a decreased negative emotional
      experience and had a speedy recovery for blood pressure, through the intermediary
      of a greater decline in total peripheral resistance, than the other groups in the
      post-task period. These results were discussed in connection with the function of
      cognitive reappraisal.

PMID- 17511247
TI  - [Pictorial depth perception in central and peripheral visual fields].
AB  - The present study aims to examine whether depth perception based on pictorial
      cues in the peripheral visual field is improved by compensating for the
      peripheral reduction of visual sensitivity. Figures that partially overlapped or
      had apparent transparency over a background figure were presented on a CRT
      monitor at the central-peripheral retinal regions of 2.5-10 degrees eccentricity
      under the two conditions of same size or size adjusted for the Cortical
      Magnification Scale (Virsu & Rovamo, 1979). In Experiment 1 the subjects could
      discriminate the depth relationship of two cortically magnified figures when
      these were presented within the retinal eccentricity of 10 degrees, even when
      solutions for the tasks were not dependent on a single visual attribute
      (brightness, shape). But discrimination in the peripheral visual field became
      difficult when the number of visual attributes of the stimuli increased
      (Experiment 2). We conclude that even for peripheral vision, depth perception
      based on pictorial cues is possible when cortically magnified stimuli are used.
      However, it should be further study whether or not the visual acuity is an only
      determinant for the difference between central and peripheral depth perception.

PMID- 17511248
TI  - [Effect of directed forgetting on false recognition: an examination of the
      activation-monitoring hypothesis].
AB  - This study examined the influence of directed forgetting on false recognition.
      Participants studied one of two types of lists consisting of words related to a
      critical non-presented (CN) word: high or low semantic-associative-strength
      lists. Thirty-one participants were instructed to forget the Ist list before
      studying the 2nd list (forget group), another group of 30 participants were
      instructed to remember both lists (remember group). This was followed by a
      recognition test and Remember/Know judgments. For CN words, the forget group
      showed more false recognition than the remember group only for high semantic
      associative-strength lists. Moreover, higher proportions of Remember judgments
      were observed than Know judgments in false recognition responses. These findings
      are discussed in terms of the activation-monitoring hypothesis of false memories.

PMID- 17511249
TI  - [Effects of retrieving context information on accuracy-confidence relationships
      in recognition memory for faces].
AB  - We investigated how retrieval conditions affect accuracy-confidence (A-C)
      relationship sin recognition memory for faces. Seventy participants took a face
      recognition test and rated their confidence in their judgment. Twenty-three
      participants were assigned to a retrieval condition, where they were encouraged
      to remember background information (scenery) of each picture just before rating
      their confidence. Twenty-four participants were assigned to a verbalizing
      condition, in which they were encouraged to remember and verbally describe the
      background of each picture before rating. Twenty-three participants were assigned
      to a control condition. The results showed that for the control condition, an A-C
      relationship was found for old items but not for new items, replicating the
      results of Takahashi (1998) and Wagenaar (1988). In contrast, in the retrieval
      condition, an A-C relationship was found for both old and new items. In the
      verbalizing condition, an A-C relationship was not found for either old or new
      items. The results showed that retrieving background information affects A-C
      relationships, supporting the idea that confidence ratings rely not only on
      memory traces but also on various kinds of information such as retrieved
      background scenery. Implications for eyewitness testimony were discussed.

PMID- 17511250
TI  - [Different styles of influence tactics affect the likelihood of receiving support
      from peers].
AB  - This study examines how the use of influence tactics between peers affects the
      likelihood of eliciting social support. The participants (261 college students)
      were asked to imagine themselves in one of six scenarios, which described a
      hypothetical peer agent who usually uses specific influence tactics and the
      strength of the friendship. Then the participants rated the likelihood of
      supporting the agent, when the agent confronted a stressful situation. The result
      shows that the participants gave less spontaneous support to an agent who used
      hard influence tactics, such as restricting their freedom in choosing a course of
      action. Regarding emotional support, when they are in a close relationship with
      the agent, the participants gave the most spontaneous support to the agent using
      soft influence tactics, such as ingratiation. Participants gave steady socio
      emotional support to agents using rational influence tactics, regardless of their
      relationship. This study also examined how influence tactics affect the
      participants' impression of the agent.

PMID- 17511251
TI  - [Pathogenic gene in an inherited peroxisome disorder and its cellular
      dysfunction].

PMID- 17511252
TI  - [New-generation gene targeting technique: its problems and prospects].

PMID- 17511253
TI  - [Structure, function, and stability of cytolethal distending toxin].

PMID- 17511254
TI  - [Structures of multiple-domain chitinases].

PMID- 17511255
TI  - [Immunomodulation by modified glycolipid ligand-stimulated invariant natural
      killer T (iNKT) cells].

PMID- 17511256
TI  - [Histone methylation and transcriptional regulation].

PMID- 17511257
TI  - [Crystal structure of polypeptide-GalNAc transferases: lectin domain and
      catalytic domain].

PMID- 17511258
TI  - [Function of neuroglycan C (NGC), a brain-specific chondroitin sulfate
      proteoglycan].

PMID- 17511259
TI  - [Neuropeptide PACAP and neuropsychological function: unexpected insights from
      mouse mutants].

PMID- 17511260
TI  - [Improvement of a multi-target screening analysis for drugs using a QTRAP liquid
      chromatography/tandem mass spectrometry system].
AB  - We have investigated the usefulness of an improved multi-target screening method
      based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis on a
      hybrid triple-quadrupole linear ion trap mass spectrometer for detecting major
      drugs in toxicological analysis. Fifteen drugs, most frequently detected in
      intoxicated patients treated at the emergency medicine section in our institute,
      were mixed together in serum or urine at concentration of 100 ng/ml each, and
      then extracted by liquid-liquid extraction using 1-chlorobutane, followed by an
      analysis using LC/MS/MS. By setting the collision energy at the multiple reaction
      monitoring mode and declustering potential at the enhanced product ion scan mode
      individually for each drug, clinically satisfactory sensitivity was attained for
      the detection of drugs in extracted samples. The results of the present study on
      several serum/urine samples of intoxicated patients indicated that this method is
      superior to other screening methods in reliability. Taken together, our improved
      LC/MS/MS analysis is useful for detecting major drugs causing intoxication in the
      field of emergency medicine.

PMID- 17511261
TI  - [A simple separative method for measuring serum amyloid A in high-density
      lipoprotein and low-density-lipoprotein fractions using the phosphotungstic acid
      Mg2+ precipitation procedure].
AB  - We developed a simple separative method for measuring serum amyloid A (SAA) in
      both high-density-lipoprotein (HDL) and low-density-lipoprotein (LDL) fractions.
      It was devised using the SAA agglutination method and phosphotungstic acid-Mg2+
      precipitation procedure for evaluating HDL-cholesterol (HDL-C). The new method is
      also able to detect amyloid A (AA) in each fraction with precision. The results
      of both the present method and the method using SAA agglutination and the dextran
      sulfate-Mg2+ precipitation procedure showed a strong correlation when used to
      measure the level of SAA in the LDL fraction of patients (r = 0.997; p < 0.0001).
      Reference intervals in normal healthy subjects (n=75) ranged from 0.5 to 4.7
      microg/ml in the HDL fraction and from 0.1 to 1.9 microg/ml in the LDL fraction.
      SAA in the LDL fraction of subjects with hyperlipidemia was significantly higher
      than in normal subjects and subjects with normal lipidemia. SAA in the HDL
      fraction and total sera of subjects with hyperlipidemia was significantly higher
      than in normal subjects; however, it was not higher than in patients with normal
      lipidemia. The present methods for detecting SAA, especially in the LDL fraction,
      might benefit from analyzing patho-physiological events in various lipid
      disorders.

PMID- 17511262
TI  - [The mechanism of TRACP 5b maturation].
AB  - Serum tartrate resistant acid phosphatase 5b (TRACP 5b) is an isozyme of
      osteoclast origin. Indeed, measurement of TRACP 5b activity is used as an index
      of osteoclast activity. However, the precise mechanism of TRACP 5b maturation is
      unclear. This study aimed to clarify the mechanism of generation of TRACP 5b. We
      used a highly sensitive fiber-type DNA chip to investigate the mechanism of
      generation of TRACP 5b at the genetic level. Genes derived from three related
      cell types (monocytes, macrophages and osteoclasts) were compared. In addition,
      at the protein level, posttranscriptional modification was tested by Western
      blotting using an antiserum specific for the flexible loop region of TRACP 5. Our
      DNA chip study shows that genes implicated in oligosaccharide construction do not
      show significant differences in expression levels between the cell types under
      investigation. Strongly expressed Cathepsin K was observed in osteoclasts.
      Western blotting demonstrated that TRACP undergoes unique partial degradation
      during bone resorption, such that serum TRACP 5b lacks the flexible loop found in
      TRACP 5a. In conclusion, TRACP 5b generated by a specific posttranscriptional
      modification pathway undergoes partial digestion in resorption lacunae or inside
      osteoclasts. Serum TRACP 5b lacking the flexible loop differs from TRACP 5a in
      terms of optimum pH, isoelectric point, sugar chain and antigenicity. The
      measurement of TRACP 5b could therefore be of great use for monitoring of
      osteoporosis, rheumatoid arthritis and bone metastasis.

PMID- 17511263
TI  - [False positive serum des-gamma-carboxy prothrombin after resection of
      hepatocellular carcinoma].
AB  - Measurements of serum concentrations of des-gamma-carboxy-prothrombin (PIVKA-II)
      are widely used for diagnosing hepatocellular carcinoma (HCC). Recently, when we
      evaluated the correlation of PIVKA-II between two commercially available PIVKA-II
      immunoassay kits (Lumipulse f vs. Picolumi) to introduce it in our hospital,
      false high values of PIVKA-II were observed in Lumipulse assay. Four(4%) of 100
      serum samples showed false high values, and all of them were obtained from
      patients less than 2 month after curative resection of HCC. Examining additional
      7 patients with HCC resection, serum samples from the 5 patients had the same
      trend. To elucidate the non-specific reaction by Lumipulse assay which utilized
      alkaline phosphatase (ALP) enzymatic reaction, inhibition assays by various
      absorbents such as inactive ALP and IgM antibodies were performed. Excess of
      inactive ALP reduced the high values of PIVKA-II. Note that anti-bleeding sheets
      (fibrinogen combined drug), which included bovine thrombin, were directly
      attached on liver of all patients with HCC resection in this study. As the sheets
      also contaminate ALP and probably produce IgM antibodies to ALP, the IgM may
      cross-react with anti-PIVKA-II antibodies directly. Taken together, it was
      suggested that produced antibodies against ALP derived from anti-bleeding sheets
      led false high values of PIVKA-II in the patients with HCC resection.

PMID- 17511264
TI  - [Clinical significance of thiazide-sensitive Na-Cl cotransporter gene by
      mutational analysis].
AB  - Thiazide-sensitive Na-Cl cotransporter (TSC, SLC12A3) is located on chromosome
      16q13 and is expressed specifically in the renal distal convoluted tubule, where
      it mediates the reabsorption of Na+ and Cl-. Mutation of TSC is known to be
      responsible for Gitelman's syndrome, an autosomal recessive renal tubular
      disorder characterized by low blood pressure due to renal sodium wasting,
      hypokalemia, metabolic alkalosis, hypomagnesemia and normocalcemic hypocaliuria.
      We assessed mutational analysis of the TSC gene in 35 patients with Gitelman's
      syndrome. We found 16 missense mutaions, insertion of 18bp in the 6th exon,
      deletion of C in the 9th exon and deletion of C in the 16th exon. These results
      suggest that there is no mutational hot spot in the TSC gene. These 19 mutations
      include eight novel mutations: R261C, N406H, A523T, M672I, R1009Q, N1014K,
      deletion of C in the 9th exon and deletion of C in the 16th exon. The eight novel
      mutations might be responsible for impairment of NaCl reabsorption leading to the
      principal clinical features of Gitelman's syndrome in these patients. These
      mutations could bring new insights into genotype-phenotype correlations among the
      hypokalemic tubulopathies. Recently, genome-wide association studies, using SNPs
      to identify loci involved in susceptibility to common diseases, showed that the
      TSC gene may contribute to genetic susceptibility to diabetic nephropathy in
      Japanese. In addition, substitution of Arg904 to Gln in the TSC gene has been
      reported to predispose essential hypertension in Swedish and Japanese
      populations. Further studies are needed to clarify the possible associations of
      the TSC gene with common diseases.

PMID- 17511265
TI  - [Progression in diagnostic pathology; development of virtual microscopy and its
      applications].
AB  - Many systems have already been designed and successfully used for clinical
      laboratory and pathological examination. The evolution of image analysis was
      enabled when analog images of the original glass slides could be transferred to
      digital images with the rapid development of virtual microscopy and virtual
      slides depended upon computer technologies. Today, whole slide can be acquired by
      virtual microscopes. The applications of virtual microscopy and virtual slides
      for teaching, diagnosis, telepathology, and research are more widely used than
      those of real microscope and real glass slides. In traditional cancer diagnosis,
      pathologists examine biopsies to make diagnostic assessments largely based on two
      dimensional cell morphology and tissue distribution. These assessments are
      subjective and often show considerable variability. However, automated cancer
      diagnostic system based on three-dimensional image analysis based on nuclear
      bulging sign enables objective judgments using quantitative measurements. We
      expect that the shortage of pathologists will be improved when an automated
      cancer diagnosis system is developed.

PMID- 17511266
TI  - [Measurement of sphingosine 1-phosphate as a biomarker of atherosclerosis].
AB  - Sphingosine 1-phosphate (S1P) is concentrated in lipoprotein, especially high
      density lipoprotein (HDL), in plasma. We characterized the role of HDL-associated
      S1P in HDL-induced anti-atherogenic effects. HDL-associated S1P mediated HDL
      induced stimulation of proliferation, migration and inhibition of apoptosis
      through S1P specific receptors S1P1 and/or S1P3 in endothelial cells. On the
      other hand, HDL-induced nitric oxide production and inhibition of adhesion
      molecule expression were mediated by two pathways, i.e, HDL-associated apoprotein
      A-I, A-II/SR-BI and S1P/S1P receptors in endothelial cells. Thus, in endothelial
      cells, HDL-associated S1P is a key player of HDL-induced anti-atherogenic
      effects.

PMID- 17511267
TI  - [Ultrasonic measurement of arterial wall for quantitative diagnosis of
      atherosclerosis--elasticity imaging of arterial wall and atherosclerotic plaque].
AB  - To provide useful information for the diagnosis of atherosclerosis in addition to
      the imaging of morphology using B-mode ultrasonography, we have developed a
      method, namely, the phased-tracking method, to measure the small change in the
      thickness of the arterial wall due to the heartbeat. This change in thickness
      corresponds to strain due to the change in internal pressure, and the elasticity
      of the arterial wall is obtained by the simultaneous measurement of the change in
      thickness and pulse pressure. Furthermore, an elasticity image can be classified
      into tissue components using the reference data obtained by in vitro experiments
      because the elastic properties are different among the tissue components in the
      arterial wall. We have measured the elasticity distributions of lipids, blood
      clots, fibrous tissue, and calcified tissue in vitro. From these results, it was
      found that arterial tissues can be classified into soft tissues (lipids, blood
      clots) and hard tissues (fibrous tissue, calcified tissue) on the basis of their
      elasticity. However, it is difficult to differentiate lipids from blood clots and
      fibrous tissue from calcified tissue because the elasticity distributions of
      these components overlap each other. To overcome this problem, we proposed a
      tissue classification method in which, the elasticity distribution of each small
      region of interest (not a single pixel) in an elasticity image was used in the
      classification of lipids, blood clots, fibrous tissue, and calcified tissue,
      respectively. Tissue classification results obtained by this method showed good
      agreement with the pathological image of the corresponding section.

PMID- 17511268
TI  - [Clarification of the pathogenesis and development of clinical examination for
      allergic diseases].
AB  - The incidence of allergic diseases has dramatically increased in recent decades
      in Japan; therefore, it is important to establish ways to diagnose allergic
      patients based on their pathogenesis and to treat them. Allergic diseases are
      complicated and diverse disorders in which various cells and mediators are
      involved; however, it is widely accepted that they are Th2-type inflammations
      triggered by the invasion of allergens. It is known that either IL-4 or IL-13,
      particularly the latter, has an important role in the pathogenesis of bronchial
      asthma among Th-2 type cytokines; however, it is unclear how IL-4 or IL-13 causes
      asthmatic phenotypes. We have been trying to address this question by using
      microarray analysis. We have recently found that periostin, identified as an IL
      4/IL-13-inducible gene by microarray analysis, is a novel component of
      subepithelial fibrosis of bronchial asthma. This finding is important to
      demonstrate the significance of IL-4 and/or IL-13 as a therapeutic target to
      inhibit fibrosis in bronchial asthma. Furthermore, it is also important to
      establish a way to diagnose allergic patients in which IL-4 or IL-13 is
      dominantly involved, and to apply the developing IL-4/IL-13 inhibitors to these
      patients. In this article, we show how we are addressing this issue.

PMID- 17511269
TI  - [The utility of exhaled breath condensate analysis for asthma management].
AB  - Asthma is a chronic inflammatory disorder of the airways; therefore, establishing
      a simple monitoring system of airway inflammation would be useful for asthma
      management. Exhaled breath condensate (EBC), which is formed by breathing with a
      cooling system, is a non-invasive biomarker for airway inflammation. We have
      shown that nine kinds of molecules; namely, IL-4, IL-8, IL-17, TNF-alpha, RANTES,
      IP-10, TGF-beta, MIP-1alpha, and MIP-1beta, are over-expressed in asthmatic
      airways compared with those of healthy subjects using EBC analysis. In addition,
      the levels of some over-expressed molecules and lung physiologic indices are
      correlated. RANTES expression was significantly correlated with the degree of
      airflow limitation. Further, both TNF-alpha and TGF-beta values were
      significantly correlated with the degree of airway responsiveness and variability
      of peak expiratory flow. Additionally, the comparison of molecular properties
      between EBC and saliva indicated that saliva contamination is not a dominant
      contributor to the assessment of inflammatory molecules in EBC. Analysis of
      inflammatory molecules using EBC should be useful for monitoring the asthmatic
      airway condition, and might be a promising approach to assess the efficacy of
      pharmacologic interventions and to investigate the pathophysiology of asthma.

PMID- 17511270
TI  - [Immunity tests for respiratory diseases--SP-A, SP-D, KL-6].
AB  - We present the measurement methods, physiological means and clinical utilities of
      surfactant protein-A (SP-A), surfactant protein-D and KL-6 of current immunity
      tests for pulmonary diseases in Japan. The measurement methods of SP-A and SP-D
      are Enzyme Immunoassays(EIA), and SP-D cannot be measured automatically. KL-6 can
      be measured directly by the Sandwich method, developed in 1985 by our co
      researcher Professor Kohno. SP-A and SP-D, proteins in pulmonary surfactants
      (phosphoric lipids), can kill many causative bacteria of respiratory infectious
      diseases by the activation of natural immune defective functions of macrophages.
      KL-6 is MUC-1, which responded to sixth antibodies extracted from lung cancer
      cells by Professor Kohno's monoclonal antibody method. SP-A, SP D and KL-6 are
      very used in the clinical field as injury markers of the lungs, because they have
      been proved to increase abnormity in difficult pulmonary fibrotic diseases such
      as idiopathic interstitial pulmonitis (IIP), etc. In particular, we could prove
      that KL-6 increased the movement and volume of pulmonary fibroblastic cells and
      decreased the apoptosis of pulmonary fibroblastic cells. In the near future, we
      are planning to develop new therapeutic drugs for pulmonary fibrotic diseases, as
      the target the fibrotic mechanism of the lungs by KL-6.

PMID- 17511271
TI  - [New diagnostic and evaluative tests for rheumatoid arthritis].
AB  - To prevent joint destruction, it is important to diagnose RA early and to
      consider the prognosis. For this purpose, several new laboratory tests, such as
      IgG-RF, anti-agalactosyl IgG antibodies (CARF), and matrix metalloproteinase-3
      (MMP-3), have become available for diagnosing RA. RF has a tolerable sensitivity
      of 68.5% for RA, but low specificity of 77.1%, and also 76.0% for patients with
      other rheumatic diseases and chronic inflammatory disease, respectively. CARF
      showed slightly higher sensitivity but low specificity for other rheumatic
      diseases and chronic inflammatory patients. In contrast, anti-cyclic
      citrullinated peptide antibody (anti-CCP), a new diagnostic test for RA,
      demonstrated significantly high specificity for other rheumatic diseases, and
      also for chronic inflammatory disease patients. Anti-CCP was superior to other
      laboratory tests by ROC analysis. Moreover, both CARF and anti-CCP had higher
      sensitivity of 66.7%, 61.5%, respectively, for the diagnosis of early RA than RF.
      On the other hand, MMP-3 is thought to be not only an evaluative test for the
      activity of RA because of its significant correlation with CRP, but also has
      potential as a prognostic test to identify joint damage from RA. Anti-CCP was
      also reported to associate with the progression of joint damage and may be also
      used as a prognostic test. We next examined the efficiency of RA diagnosis made
      by combining these laboratory tests. The specificity of RF was not as high as
      anti-CCP but reached 92% when combined with MMP-3. Thus, it is concluded that
      anti-CCP is superior to other laboratory tests in sensitivity and specificity,
      and that these combination assays are useful in the early diagnosis of RA.

PMID- 17511272
TI  - [Case of consciousness disturbance following a fever with spreading lesion over
      the bilateral splenia of the corpus callosum on MRI].
AB  - We report a 66-year-old man with spreading lesion over the bilateral splenia of
      the corpus callosum shown on MRI. On admission, unknown fever and myoclonus-like
      involuntary movement in the left forefinger and middle finger were observed.
      There were no remarkably abnormal data in the serum, the cerebrospinal fluid and
      electroencephalogram. However, T2-weighted MRI revealed the high signal spreading
      over the bilateral splenia of the corpus callosum, while enhanced effects were
      not observed by Gd contrast on T1-weighted MRI. Diffusion and FLAIR MRI also
      showed the high signals limited to the same part of the splenia bilaterally as on
      T2-weighted MRI, discriminating it from other lacunar lesions and old cerebral
      infarctions. Neurological features, which were considered to be directly
      associated with the fresh lesion, were impairment of verbal and visual memories.
      Near the time the therapies including high-dose steroid were given, the
      consciousness of the patient worsened rapidly on a day-to-day basis and
      disseminated intravascular coagulation syndrome (DIC) also occurred. By
      administering low-molecule heparin, consciousness disturbance and involuntary
      movements recovered completely. Following the improved symptoms, FLAIR MRI showed
      a reduced level of the signal seven months after the onset. A demyelinating
      disease over the bilateral splenia of the corpus callosum should be considered as
      the final diagnosis. Follow-up of the changes in this case is expected to provide
      a more accurate diagnosis.

PMID- 17511273
TI  - [Case of methotrexate encephalopathy: findings on diffusion tensor image and
      correlation with clinical outcome].
AB  - Methotrexate (MTX) is a major cause of treatment-related acute neurotoxicity. We
      report on clinical and imaging findings of reversibly restricted diffusion in a
      patient with transient encephalopathy after high dose MTX therapy for
      osteosarcoma. During the chemotherapy, a 19-year-old man was introduced for the
      evaluation of consciousness disturbance. Neurological examination revealed
      confusion, inability of speak at the onset On next day, there were still
      difficulties in swallowing and phonation, and furthermore deep tendon reflexes
      were hyperactive in bilateral lower limbs with positive Babinski responses
      bilaterally. By the 6th day, findings at neurological examination were completely
      normal. Initial imaging on presentation was performed using MRI. Diffusion
      weighted MRI clearly indicated areas of restricted diffusion within both centrum
      semiovale. These abnormalities were confirmed by the diffusion tensor (DT)
      technique (ADC and FA map). The follow-up MRI examinations using same protocol
      showed resolution of the ADC and FA abnormalities but increasing T2-signal
      changes. Neither contrast enhancement nor atrophy was encountered. Early
      detection of MTX white matter injury by DT image has the potential to alert the
      oncologist and neurologist to this event and provide a technique by which
      treatment of neurotoxicity can be monitored.

PMID- 17511274
TI  - [Case report of Wegener's granulomatosis presenting with multiple cranial nerve
      palsy and hypertrophic cranial pachymeningitis].
AB  - We report a 41-year-old man whose initial neurological symptoms are atypical of
      Wegener's granulomatosis. The patient was admitted because he developed left
      ocular pain, headache, bilateral visual loss and left abducens nerve palsy. He
      was initially diagnosed with optic neuritis at ophthalmological department and
      steroid therapy was started. Although steroid therapy led to rapid recovery of
      visual acuity and eye movement, he was readmitted for seizure. Two weeks later, a
      second seizure attack occurred, followed by palsy of the left side of cranial
      nerves II, III, IV, V and VI. Brain MRI showed focal thickening and enhancement
      of the dura mater over left frontal lobe, leading to a new presumptive diagnosis
      of idiopathic hypertrophic cranial pachymeningitis. Steroid therapy was resumed
      and the symptoms improved rapidly. As right hemiparesis developed during the
      clinical course, another brain MRI was obtained. T2-weighted image showed a high
      intensity area in the left portion of the pons. 14 months later, recurrent
      epistaxis suggestive of Wegener's granulomatosis appeared. A subsequent
      nasopharyngeal mucosa biopsy revealed a necrotizing granulomatous inflammation. A
      significant elevation of PR-3 ANCA was also noted. A definitive diagnosis of
      Wegener's granulomatosis was established. The initial presentation of this case
      was of multiple cranial neuropathies with no superior respiratory tract symptoms,
      which are typical of early stage Wegener's granulomatosis. In patients with
      various central nervous system symptoms and MRI evidence of hypertrophic cranial
      pachymeningitis, a thorough clinical workup of vasculitis syndrome including
      Wegener's granulomatosis should be considered.

PMID- 17511275
TI  - [Syrinx formation secondary to cervical epidural abscess].
AB  - We report a patient with syrinx formation secondary to cervical epidural abscess,
      cervical spondylitis, cervical discitis and meningitis. A 53-year-old woman
      developed sudden fever, headache and neck pain. On admission, neurological
      evaluation showed limitation of cervical motion, meningeal irritation, and
      exaggerated muscle stretch reflexes in all four extremities. Cerebrospinal fluid
      cell count was 832/mm3 and protein was 771 mg/dl. Bacterial culture of the
      cerebrospinal fluid showed Staphylococcus aureus. A cervical MRI scan with Gd
      enhancement revealed focal high intensity signal in the T2-weighted and FLAIR
      images, at the anterior meninges of the C3-8 segments, the vertebral bodies of C5
      6 and the intervertebral disks of C5-6 segment. Her diagnosis was cervical
      epidural abscess, cervical spondylitis, cervical discitis and meningitis.
      Antibiotics and steroids improved her symptoms. Six weeks after the onset of
      symptoms, a cervical MRI scan showed narrowing and synarthrosis in the
      intervertebral space between C5 and C6. MRI and myelo CT scans demonstrated a
      newly-formed syrinx from C3-C 7. This was an interesting case of syrinx formation
      secondary to cervical epidural abscess.

PMID- 17511276
TI  - [Apperceptive form visual agnosia caused by anti-TNFalpha therapy to rheumatoid
      arthritis].
AB  - TNFalpha plays an important role as an inflammatory mediator in both several
      autoimmune diseases and multiple sclerosis. Anti-TNFalpha antibody has been
      widely used to treat rheumatoid arthritis and Crohn's disease. On the. other
      hand, anti-TNFalpha antibody treatment increased recurrence rate in clinical
      trials for multiple sclerosis. We report a patient with rheumatoid arthritis
      without past history of any neurological disorders, who developed diplopia,
      ataxia, and visual agnosia specific to line drawing in the course of anti
      TNFalpha antibody treatment. MRI studies detected multiple demyelinating lesions
      in the cerebral white matter and brainstem. The present case indicates that
      careful observation of neurological symptoms is important in the course of anti
      TNFalpha antibody treatment, even in patients without past history of
      demyelinating diseases.

PMID- 17511277
TI  - [Case of opticospinal multiple sclerosis showing phenotype change to conventional
      type induced by interferon beta-1b].
AB  - A 57-year-old woman who had severe opticospinal multiple sclerosis (OSMS) was
      admitted to our hospital. She had presented with visual loss and gait disturbance
      at the age of 48, and had since experienced more than 10 relapses and been
      hospitalized 9 times. Interferon beta-lb treatment (8,000,000 units on alternate
      days) had been started at her last admission. Prior to the present admission, she
      had developed left visual loss and gait difficulty after headache lasting a few
      days. Cerebrospinal fluid showed elevation of cell count (322/mm3), protein (130
      mg/dl), and myelin basic protein (462 pg/ml; normal, <102 pg/ml). On examination,
      she exhibited decreased left visual acuity, paraplegia, ataxia of the right upper
      extremity, and sensory disturbance, particularly in the lower extremities. Bowel
      and bladder disturbances were also evident Laboratory testing showed
      lymphocytopenia (420/microl), compared to a white cell count of 1700/microl just
      before initiation of interferon beta-lb1therapy. MRI revealed a new lesion in the
      cerebellum in addition to small T2-hyperintense lesions in the white matter of
      the brain;these had been noted previously. Interferon beta-1b therapy was ceased
      and she was treated using methylprednisolone pulse therapy. After the abnormal
      findings resolved, however, interferon beta-lb1therapy was restarted. Three
      months after, she exhibited right hemiparesis without facial palsy concurrent
      with lymphocytopenia. MRI showed T2-hyperintense lesions in the periventricular
      white matter, left cerebral peduncle, bilateral middle cerebellar peduncles, and
      right cerebellar hemisphere. We reduced the doses of interferon beta
      lb1immediately. Thereafter, she did not have relapse for 29 months, but her EDSS
      (expanded disability status scale) has not recovered. Although interferon beta
      lb1has been recognized as an effective drug for decreasing the relapse rate and
      severity of both secondary progressive MS and relapsing-remitting MS, the present
      case showed the possibility of interferon beta-1b being associated with phenotype
      change from OSMS to conventional MS (CMS).

PMID- 17511278
TI  - [Case of Horner's syndrome associated with ophthalmic herpes zoster].
AB  - We reported a 74-year-old man with right Horner's syndrome associated with
      ophthalmic herpes zoster. He presented acute onset of pain, swelling, vesicular
      cutaneous eruption around the right eyelid. A diagnosis of herpes zoster
      ophthalmicus was made and he was started on acyclovir 750 mg/day. Seven days
      later he manifested right abduction deficit On admission nine days later, the
      right eyelid became ptotic and the right pupil was smaller than the left There
      was gradual improvement over the next 10 days in ptosis and miosis, and over the
      next 3 weeks in the right abduction deficit. As the sympathetic nerve runs with
      the carotid artery, it partially joins the sixth nerve within the cavernous
      sinus. We have identified a patient in whom herpes zoster ophthalmicus has
      resulted in a syndrome involving the sympathetic nerves, the sixth nerve, and the
      first division of the fifth cranial nerve. As the Horner's syndrome was
      transient, we might miss the symptom in the early stage, so we should carefully
      examine the patients.

PMID- 17511279
TI  - [Case report of aseptic meningitis due to Japanese encephalitis virus].
AB  - Although Japanese encephalitis virus is mainly associated with encephalitis, it
      does cause other diseases. However, descriptions of symptomatic infections other
      than encephalitis are limited. In this study, cerebrospinal fluid (CSF) specimens
      from 21 patients with aseptic meningitis from July to October (in summer season)
      in each year from 1993 to 2005 were investigated for Japanese encephalitis virus.
      Total RNA was extracted from the specimens and amplified by nested polymerase
      chain reaction (PCR). Among the specimens, only one product had highest homology
      with Japanese encephalitis virus genotype III. The patient was a 34-year-old man
      who complained of headache and fever in July 1998. He was clinically diagnosed
      with aseptic meningitis, and the symptoms subsided spontaneously without specific
      treatment in several days. It is suggested that some cases of aseptic meningitis
      in summer could be caused by Japanese encephalitis virus.

PMID- 17511280
TI  - [Case of Hashimoto's encephalopathy with diffuse white matter lesions on
      diffusion-weighted MRI].
AB  - A 65-year-old woman was admitted to our hospital because of subacute
      deterioration of cognitive function. On admission, she presented with marked
      disorientation of time and place and inability to carry out commands. Mini-Mental
      State Examination score was 5/30. Although routine laboratory examinations
      including thyroid function, vitamin B1 and B12, serum syphilitic reaction, sIL-2
      receptor level, titers of herpes simplex and zoster viruses, and HIV antibody
      were normal, titers of anti-thyroglobulin (TG) antibodies and thyroid peroxidase
      (TPO) antibodies were elevated. Cerebrospinal fluid showed normal findings. Brain
      MRI revealed diffuse high intensity in the white matter on diffusion- and T2
      weighted images, mimicking leukoencephalopathy. We made a diagnosis of
      Hashimoto's encephalopathy, based on clinical features and high titers of anti
      thyroid antibodies. Following administration of steroid hormone, her cognitive
      impairment gradually improved, associated with decrease of the white matter
      abnormality on MRI. Hashimoto's encephalopathy should be kept in mind in the
      differential diagnosis of subacute leukoencephalopathy with cognitive decline.

PMID- 17511281
TI  - [Case of acute zonal occult outer retinopathy (AZOOR): a 15 years' mislabeling as
      retrobulbar optic neuritis].
AB  - A 30-year-old woman was admitted to Mie University Hospital for recurrence of
      sudden visual field defect with photopsia in the right eye. She had experienced
      the same episodes at the age of 15, 20, 25 and 28 years old. A diagnosis of
      retrobulbar optic neuritis had been made at each episode, but corticosteroid
      therapy failed to resolve the symptoms. Neurologic examination on admission was
      unremarkable except for the visual field defect of the right eye. Brain MRIs with
      and without gadolinium enhancement were normal. On ophthalmologic examination,
      visual acuity was normal, but the Mariotte blind spot of the right eye was
      expanded. Ophthalmoscopic examination, visual evoked potential, flicker electro
      oculogram and Hess test were normal. Multifocal electroretinogram (ERG) revealed
      reduction in the inferior temporal response of the right eye that corresponded to
      the expansion of the Mariotte blind spot These findings were consistent with
      conditions of acute zonal occult outer retinopathy (AZOOR). The visual symptoms
      of AZOOR thus resemble those of retrobulbar optic neuritis and findings of
      multifocal ERG were useful to differentiate them. AZOOR is a newly established
      condition, and it is necessary to pay more attention to AZOOR on the differential
      diagnoses of acute-onset mono ocular visual disturbances.

PMID- 17511282
TI  - [The review of 'Yakovlev' circuit].
AB  - The neuronal circuit, the so-called 'Yakovlev', is recognized as the neuronal
      connections between the orbitofrontal, temporal, amygdaloid, and thalamic
      regions, possibly relevant to emotional function. This name is well known in
      Japan, however, it is not clear how this neural circuit has become known and why
      it was named after Yakovlev. Yakovlev, himself, just emphasized the relationship
      between emotion and the limbic lobes. It might be Nauta who first clarified the
      circuitry connections between these structures. Then, it was named the
      'basolateral limbic circuit' by Livingston. The reason that the circuit had been
      called 'Yakovlev' might be related to this reference by Livingston who associated
      the circuit with the hypothesis of limbic system and emotion by Yakovlev. Recent
      sophistication in tracing methods has clarified the minimal contribution of the
      anterior cingulate gyrus to this circuit and that the projection from the
      amygdala to thalamus is unidirectional It will then be more appropriate to define
      this circuit as follows: orbital and cingulate gyri<=> temporal tip<=> amygdala=>
      mediodorsal thalamus<=> orbital and cingulate gyri. Yakovlev contributed greatly
      to identifying the possible relevance of these structures to emotion, which was
      substantiated by Nauta with his anatomical tracing between the structures. The
      name of this circuit, 'Yakovlev', would be better modified to 'Yakovlev-Nauta'.

PMID- 17511283
TI  - [A study of bulbar, upper extremity, and lower extremity motor function
      preservation at the time that respiratory symptoms appear in ALS].
AB  - OBJECTIVE: To determine which of the three motor functions (bulbar, upper
      extremities, lower extremities) was normally preserved at the time that
      respiratory symptoms occurred in amyotrophic lateral sclerosis (ALS). BACKGROUND:
      Respiratory failure is the major cause of death in ALS. The course of the disease
      progression to the onset of subjective respiratory symptom can vary from patient
      to patient and the diversity of this progression in ALS patients is not well
      understood. PATIENTS/METHODS: The subjects were 120 Japanese patients with
      sporadic ALS who were followed-up at our hospital or for whom precise information
      was available regarding death or the time that the patient required tracheotomy
      or ventilation assistance. Symptoms started: in the upper limbs in 47 patients;
      in the lower limbs in 44 patients; in the bulbar region in 22 patients; as the
      combined type (two regions involved simultaneously on initial presentation) in 6
      patients; and with respiratory symptoms in 1 patient. RESULTS: At the time of the
      appearance of respiratory symptoms, 43 patients (35.8%) had some normally
      preserved motor function. Significantly fewer patients with progressive bulbar
      palsy maintained one or more normal motor functions (14%) compared to patients
      whose disease started in the extremities (43%). Patients were divided into two
      groups depending on whether they had significant bulbar involvement at the time
      of the appearance of respiratory symptoms: 88 patients had significant bulbar
      involvement (B type), and 32 patients did not (R type). Based on the Kaplan-Meier
      survival curves, no significant difference in the median survival time was noted
      between the two groups (R type, 29.4 months vs. B type, 32.5 months; p = 0.06).
      We could not find any difference about clinical characteristics such as gender,
      onset age, initial site between R and B group. The motor functions that were
      preserved at the time of respiratory symptom onset included: bulbar function in
      32 patients (26.7%); lower extremity function in 12 patients (10%); and upper
      extremity function in only 3 patients (2.5%). The use of mechanical ventilation
      in ALS patients with one or more preserved motor functions was significantly
      higher than in those without any normally preserved motor function (p = 0.03).
      CONCLUSIONS: From a low rate of upper extremity motor function preservation,
      respiratory function deterioration appears to be related to upper-limb
      involvement, likely due to a possible link to diaphragmatic function. Advanced
      directives should carefully address the use of mechanical ventilation in patients
      without bulbar symptoms.

PMID- 17511284
TI  - [Frequent attacks of amaurosis fugax due to hemodynamic mechanism based on severe
      stenosis of the internal carotid artery].
AB  - A 74 year-old man with prostate hypertrophy developed frequent attacks of
      amaurosis fugax in the left eye. Attacks only occurred in a standing position,
      but not when sitting or lying. He had taken tamsulosin hydrochloride for prostate
      hypertrophy and had orthostatic hypotension. After stopping the administration of
      tamsulosin hydrochloride and starting anthithorombotic theraphy, his orthostatic
      hypotension disappeared and the frequency of attacks decreased. Cerebral
      angiography demonstrated 95% stenosis and distal collapse of the left internal
      carotid artery (ICA), with collateral flow to the left middle cerebral artery
      from the right ICA through the anterior communicating artery. We thus postulated
      that a hemodynamic mechanism played an important role in the development of the
      amaurosis fugax which disappeared after carotid endarterectomy.

PMID- 17511285
TI  - [A case of combined sensation disturbance and clumsiness of the left hand caused
      by an infarction localized to brodmann areas 1 and 2].
AB  - A 70-year-old woman was admitted to our hospital with a complaint of numbness and
      clumsiness of the left hand. On physical examination 23 days after the onset of
      cerebral infarction, she showed no apparent muscle weakness. Although her
      elementary somatosensory function was mostly intact with a minimal joint position
      sensation disturbance, she showed disturbances in tactile recognition, two-point
      discrimination, and weight perception. She also had difficulty in discrete finger
      movement of her left hand, especially when her eyes were closed. Brain MRI
      disclosed a small infarction localized to Brodmann areas 1 and 2 in the right
      postcentral gyrus. In the left median nerve short-latency somatosensory evoked
      potentials (s-SEPs), the N20 potential was normally evoked. This finding also
      indicated that the area 3b was preserved. The sensory symptoms observed in this
      patient were compatible with the hierarchical somatosensory processing model in
      the postcentral gyrus proposed by Iwamura et al, in which the elementary
      sensation recognized in area 3 is transferred to areas 1 and 2, and then
      processed to discriminative sensation. The disturbed discrete finger movement in
      this patient probably resulted from impaired tactile recognition which could be
      compensated for by visual information.

PMID- 17511286
TI  - [Effect of high dose pergolide mesilate on restless legs syndrome associated with
      Parkinson disease].
AB  - Restless legs syndrome (RLS) is one of the common nocturnal disturbance seen in
      Parkinson's disease (PD) patients. The prevalence of RLS with PD is greater than
      that of general populations; however, etiology of RLS in patients with PD is
      still controversial. We report a 63-year-old man with PD, who was admitted to our
      hospital with uncontrollable unpleasant feeling in both legs leading to sleep
      disturbance. At age 59, he experienced numbness and nocturnal myoclonus in his
      right foot. One year later, he developed resting tremor and bradykinesia in his
      right hand, and was diagnosed as PD. Levodopa was initiated with favorable
      response for his resting tremor and bradykinesia, however, his dysesthesia of the
      legs spread to both side and associated with an urge to move which occurs at rest
      and was ameliorated by walking. On admission, his parkinsonism was well
      controlled by 400 mg/ day of levodopa/benserazide. Polysomnography (PSG) revealed
      periodic limb movements in sleep (PLMS). Secondary RLS such as drug-induced, iron
      deficiency and uraemia, was excluded in this patient. Because levodopa did not
      improve his RLS, additional symptomatic RLS treatment was initiated. Oral dosage
      with 150 microg pergolide did not have any effect on his RLS symptoms. An
      increase up to 750 microg pergolide led to a marked reduction of symptoms.
      Repeated PSG showed significant reduction of PLMS and improved sleep efficacy.
      Usually, low dose of dopamine agonist is enough to treat RLS occurred in general
      populations. However, moderate to high dose of dopamine agonists were needed for
      our patient with RLS, indicating that pharmacological responses might be
      different between RLS in general and that associated with PD. It is important to
      consider that PD-related RLS can be treated with high dose dopamine agonist to
      obtain favorable management of nocturnal disturbances.

PMID- 17511287
TI  - [A case of a postmedian sternotomy C8 plexopathy localized with electrodiagnostic
      tests].
AB  - A postmedian sternotomy plexopathy is a C8 plexopathy following an operation that
      requires a median sternotomy, in which the C8 anterior primary ramus is injured.
      Since the clinical picture of a C8 plexopathy is quite similar to an ulnar
      neuropathy, electrodiagnostic tests are crucial for localizing the lesion and
      confirming the diagnosis. This is the first published report in Japan that shows
      the clinical picture of a postmedian sternotomy C8 plexopathy and the utility of
      electrophysiological tests to diagnose this disease. A 54 year-old man developed
      numbness in the right ring and little fingers just after an operation through a
      median sternotomy to treat an aortic dissection. His symptoms did not improve and
      he was reevaluated 11 months after the operation. Neurological examinations
      revealed a weakness of the right ulnar-innervated hand muscles, and tingling
      dysesthesia of the ring and little fingers. In electrodiagnostic tests, the ulnar
      SNAP was severely depressed on the affected side, and in addition the amplitude
      of the median SNAP over the ring finger (Med-D4) was also reduced by more than
      half of that observed in his healthy side (62% side-to-side difference). In our
      investigation of 26 control subjects, the side-to-side difference of the Med-D4
      SNAP amplitude did not exceed 50% for any subject. Needle electromyography
      revealed profuse denervation activities in the FCU, ADM and EPB, and moderately
      reduced recruitment and giant motor unit potentials in the EI. The postmedian
      sternotomy plexopathy had been long described, but its precise localization using
      modern electrodiagnostic techniques has been presented only recently in the
      literature. Our results are largely the same as those found in previous reports,
      which show the predominant involvement of the ulnar sensory and motor fibers and
      electromyographic changes in C8-radial muscles (EPB and EI). Furthermore, the
      antidromic SNAP of Med-D4 was significantly reduced in amplitude on the affected
      side, and supported the diagnosis of the C8 plexopathy. The Med-D4 method is the
      only method that can document a nonulnar C8 involvement solely by NCS. Whereas
      the potential role of the Med-D4 method has been suggested in this condition,
      this is the first report that actually showed its utility.

PMID- 17511288
TI  - [A case of apical hypertrophic cardiomyopathy complicated by cardiogenic cerebral
      embolism].
AB  - We report a patient with apical hypertrophic cardiomyopahty (AHCM) complicated by
      a cardiogenic cerebral embolism. A 56-year-old man was admitted to our hospital
      because of a transient ischemic attack. He had been diagnosed as having AHCM at
      the age of 39 years. The intravenous administration of heparin was immediately
      started; however, he developed a weakness in his right fingers on the second day.
      A brain MRI examination showed multiple small infarctions in the cortex of the
      left frontal and temporal lobes. Transthoracic echocardiography revealed the
      hypokinetic movement of the myocardium and a thrombus in the apex. We suspected
      that the hypertrophic apex had become dilated, causing the formation of the
      thrombus. He then developed a cardiogenic cerebral embolism. The thrombus in the
      apex disappeared after the continuous administration of heparin intravenously.
      Here, we emphasize that patients with AHCM in the dilatation phase must receive
      warfarin therapy to prevent cardiogenic cerebral embolism.

PMID- 17511289
TI  - [A case of acute disseminated encephalomyelitis (ADEM) associated with peripheral
      neuropathy].
AB  - A 17-year-old boy with high fever, headache, and neck stiffness was admitted to
      our hospital. Spinal fluid showed a protein level of 215 mg/dL with myelin basic
      protein (579 pg/mL), 347/ microl cells (330 mononuclear cells), and a glucose
      level of 53 mg/dL. One week later, urinary retention, flaccid paraplegia, and
      sensory disturbance below the 10th thoracic level developed. MRI of the spinal
      cord revealed swelling and T2-high intensity area in the cord at the 11th and
      12th thoracic level. Although high-dose of methylprednisolone was administered,
      consciousness disturbance and respiratory failure that required mechanical
      ventilation occurred. Bilateral abducens nerve palsy, nystagmus, and flaccid
      tetraparesis also occurred. Brain MRI revealed T2-high intensity area in the
      midbrain and pons. Nerve conduction study showed diminished amplitudes and
      prolonged latencies or absence of F waves. The patient was administered a
      combination of intravenous immunoglobulin and a high-dose of methylprednisolone.
      He showed improvement within one week after the treatment. Two weeks later, he
      recovered from respiratory failure and weakness of the upper limbs. He remained
      paraplegic, but gradually improved and was able to walk with support one and a
      half years later. We suggest the combination therapy of intravenous
      immunoglobulin and a high-dose of methylprednisolone is effective for patients
      with combined ADEM and peripheral neuropathy.

PMID- 17511290
TI  - [A case of alcoholic with vitamin B12 deficiency presenting central pontine and
      extrapontine myelinolysis on MRI].
AB  - A 55-year-old man with chronic alcoholism was first referred to us in 1992
      because of spastic quadriparesis. T2-weighted images of MRI showed pontine and
      extracapsule lesions as central pontine and extrapontine myelinolysis (CPM/EPM).
      He had macrocytic anemia with normal serum level of vitamin B12 (B12). Gait
      disturbance was progressively worsened from the end of 2004 and dysuria appeared
      from June, 2005. Neurological examination on admission in November, 2005, showed
      mild impairment of recent memory, spastic paraparesis with hyperreflexia in all
      limbs, loss of deep sensations in lower limbs and urinary disturbance. The low
      serum level of B12 with marked macrocytic anemia was noted. On MRI. the pontine
      lesion extended to the midbrain but no abnormality was found in the spinal cord.
      We intramuscularly administered B12, resulting in marked improvement of both
      anemia and neurological symptoms. The brainstem lesion on MRI, however, was
      unchanged. We assume that B12 deficiency was involved in the formation of CPM/EPM
      and the neurological symptoms in our patient.

PMID- 17511291
TI  - [Distigmine bromide improves chronic intestinal pseudo-obstruction in a case of
      MELAS].
AB  - A 34-year-old man with MELAS (mitochondrial myopathy, encephalopathy, lactic
      acidosis, and stroke-like episodes) showed chronic intestinal pseudo-obstruction
      (CIPO), which was improved by the administration of distigmine bromide. He
      exhibited generalized tonic clonic seizures at the age of 21, and mitochondrial
      DNA analysis showed the MELAS mutation. At the age of 34, he became akinetic
      mutism after nonconvulsive status epilepticus and needed enteral nutrition
      through a nasogasrtic tube. However, he developed abdominal distention and
      vomiting, and was diagnosed as CIPO, therefore tube feeding was stopped. Although
      the administration of domperidone, mosapride citrate, butyric acid bacteria,
      sodium picosulfate, prostaglandin F2 alpha, pantothenic acid, dioctyl sodium
      sulfosuccinate, and so on, was ineffective, the administration of distigmine
      bromide improved his bowel motion disturbance and abnormal distention. The
      present case is the first MELAS patient with CIPO to be ameliorated by distigmine
      bromide, which might work acetylcholine receptor on the interstitial cells of
      Cajal.

PMID- 17511292
TI  - Space medicine roots: a historical perspective for the current direction.

PMID- 17511293
TI  - Acute urinary retention among astronauts.
AB  - Although acute urinary retention (AUR) is not commonly thought of as a life
      threatening condition, its presentation in orbit can lead to a number of medical
      complications that could compromise a space mission. We report on a middle-aged
      astronaut who developed urinary retention during two spaceflights. On the first
      mission of note, the astronaut initially took standard doses of promethazine and
      scopolamine before launch, and developed AUR immediately after entering orbit.
      For the first 3 d, the astronaut underwent intermittent catheterizations with a
      single balloon-tipped catheter. Due to the lack of iodine solution on board and
      the need for the astronaut to complete certain duties without interruption, the
      catheter was left in place for a total of 4 d. Although the ability to void
      returned after day 7, a bout of AUR reemerged on day 10, 1 d before landing. On
      return to Earth, a cystometrogram was unremarkable. During the astronaut's next
      mission, AUR again recurred for the first 24 h of microgravity exposure, and the
      astronaut was subsequently able to void spontaneously while in space. This report
      details the presentation of this astronaut, the precautions that were taken for
      space travel subsequent to the initial episode of AUR, and the possible reasons
      why space travel can predispose astronauts to urinary retention while in orbit.
      The four major causes of AUR--obstructive, pharmacologic, psychogenic, and
      neurogenic-are discussed, with an emphasis on how these may have played a role in
      this case.

PMID- 17511294
TI  - Renal stone formation among astronauts.
AB  - INTRODUCTION: With the continued construction of the International Space Station,
      humans are living longer in the microgravity environment of space. However, many
      questions still exist as to the physiological effects of spaceflight on the human
      body. Bone loss, cardiovascular changes, and muscle atrophy are well-documented
      health risks to humans during spaceflight. Another potential serious health
      complication is the development of renal stones. The development of a renal stone
      may not only impact the health of the crewmember, but also the success of the
      mission. METHODS: A retrospective analysis of astronaut data from 24-h urine
      samples collected prior to launch and immediately after landing was performed.
      Urine characteristics associated with renal stone formation were analyzed and the
      relative injury supersaturations of stone-forming constituents calculated.
      RESULTS: In the current study, previously collected data to identify urinary
      factors associated with renal stone formation demonstrated an increased risk in
      astronauts who had actually formed a renal stone. Increased urinary
      supersaturation of the stone-forming salts was observed in those astronauts who
      formed renal stones. Similar changes in urinary supersaturation were noted among
      many astronauts after landing, indicating an increased postflight risk for stone
      formation. CONCLUSIONS: An assessment program should be undertaken to identify
      and evaluate astronauts with elevated risk factors prior to flight and
      immediately following landing. Individualized recommendations can be prescribed
      to astronauts and may include dietary changes, increased fluid intake, or
      medications to minimize the risk of stone formation.

PMID- 17511295
TI  - Physiologic effects of simulated + Gx orbital reentry in primate models of
      hemorrhagic shock.
AB  - INTRODUCTION: While the physiologic effects of space travel are documented in
      healthy individuals, little is known about its impact on medically ill or injured
      persons. In this study, hemorrhagic shock in primates was used to model a
      potentially common pathophysiologic condition during exposure to gravitational
      forces simulating return from Earth orbit. This experiment did not model the
      effects of cardiovascular deconditioning that normally occur during spaceflight.
      METHODS: Using invasive hemodynamic monitoring, serial cardiovascular and
      laboratory parameters in baboons (Papio papio) were studied. Subjects were
      centrifuged at either a low +Gx (3.3 G maximum) or high +Gx (7.8 G maximum)
      acceleration reentry profile before and after being subjected to either class II
      (20% volume loss) or class IV (40% volume loss) hemorrhagic shock. RESULTS:
      Significant alterations in cardiovascular and laboratory parameters occurred
      during shock and exposure to high and low +Gx acceleration. Shock classification
      was the primary determinant of change in cardiovascular function. During the
      experimental protocol, 31 of 32 animals survived (97% survival). After a 1-wk
      post-protocol observation period, 28 of 32 subjects survived (88% survival).
      CONCLUSIONS: This preliminary study presents data that suggest that the emergent
      return of a medically compromised individual without resuscitation may be
      potentially survivable. However, medical stabilization with volume resuscitation,
      supplemental oxygen, and noninvasive monitoring would likely optimize clinical
      outcomes in the event of significant hemorrhagic shock states necessitating
      emergent deorbit.

PMID- 17511296
TI  - Breast cancer and spaceflight: risk and management.
AB  - Spaceflight exposes astronauts to a host of environmental factors which could
      increase their risk for cancer. Epidemiological studies have shown an increased
      incidence of breast cancer in female commercial flight attendants, with
      occupational risk factors as one of the proposed mechanisms for the higher
      incidence in this cohort. Since female astronauts are exposed to similar
      occupational conditions as flight attendants, they too may be at an increased
      risk for breast cancer. With the planning of exploration class missions to the
      Moon and to Mars it is important to assess and minimize the risk for breast
      malignancy, and to have a well-defined protocol for the diagnosis and treatment
      of a breast mass discovered during a mission. Risk factors for development of
      breast cancer in the female astronaut include ionizing radiation, disrupted
      melatonin homeostasis secondary to circadian shifting, chemical exposure, and
      changes in immune function. Preflight, in-flight, and postflight screening and
      management modalities include imaging and fine needle aspiration (FNA). Employing
      such a strategy may provide a viable management approach in the case of a newly
      diagnosed breast mass inflight.

PMID- 17511297
TI  - Trauma sonography for use in microgravity.
AB  - Sonography is the only medical imaging modality aboard the ISS, and is likely to
      remain the leading imaging modality in future human spaceflight programs. While
      trauma sonography (TS) has been well recognized for terrestrial trauma settings,
      the technique had to be evaluated for suitability in spaceflight prior to
      adopting it as an operational capability. The authors found the following four
      phased evaluative approach applicable to this task: 1) identifying standard or
      novel terrestrial techniques for potential use in space medicine; 2) developing
      and testing these techniques with suggested modifications on the ground (1 G)
      either in clinical settings or in animal models, as appropriate; 3) evaluating
      and refining the techniques in parabolic flight (0 G); and 4) validating and
      implementing for clinical use in space. In Phase I of the TS project, expert
      opinion and literature review suggested TS to be a potential screening tool for
      trauma in space. In Phase II, animal models were developed and tested in ground
      studies, and clinical studies were carried out in collaborating trauma centers.
      In Phase III, animal models were flight-tested in the NASA KC-135 Reduced Gravity
      Laboratory. Preliminary results of the first three phases demonstrated the
      potential clinical utility of TS in microgravity. Phase IV studies have begun to
      address crew training issues, onboard imaging protocols, and data transfer
      procedures necessary to offer the modified TS technique for space use.

PMID- 17511298
TI  - 16S rRNA beacons for bacterial monitoring during human space missions.
AB  - Microorganisms are unavoidable in space environments and their presence has, at
      times, been a source of problems. Concerns about disease during human space
      missions are particularly important considering the significant changes the
      immune system incurs during spaceflight and the history of microbial
      contamination aboard the Mir space station. Additionally, these contaminants may
      have adverse effects on instrumentation and life-support systems. A sensitive,
      highly specific system to detect, characterize, and monitor these microbial
      populations is essential. Herein we describe a monitoring approach that uses 16S
      rRNA targeted molecular beacons to successfully detect several specific bacterial
      groupings. This methodology will greatly simplify in-flight monitoring by
      minimizing sample handling and processing. We also address and provide solutions
      to target accessibility problems encountered in hybridizations that target 16S
      rRNA.

PMID- 17511299
TI  - Thermoregulatory models of space shuttle and space station activities.
AB  - BACKGROUND: Thermoregulation is critical for survival in space, especially during
      contingencies demanding of human cognitive and physical performance. A review of
      the negative feedback human thermoregulatory system is provided. The Advanced
      Crew Escape Suit is worn by astronauts during ascent and descent on the Space
      Shuttle to provide active cooling for nominal and contingency operations and
      protection from loss of cabin pressure mishaps. Failure of a thermal system
      control element during a recent Shuttle flight resulted in a single point failure
      that could have elevated cabin temperature, possibly resulting in cognitive
      deficits of the pilot during the reentry and landing phases. METHODS: The
      efficacy of the existing cooling equipment and procedures for maintaining crew
      thermal comfort in the event of such a failure was assessed. The Wissler and 41
      node thermoregulatory models were used to conduct a parametric study of Shuttle
      cabin temperatures and resulting thermal effects on crew. RESULTS: Under high
      metabolic loads, crewmember core temperatures and heat storage are shown to
      increase beyond allowable limits using this analysis. Resulting levels of thermal
      stress may exceed standardized limits, after which cognitive performance and
      manual tracking ability are diminished. DISCUSSION: The operational procedure for
      entry and landing during this failure scenario may result in significant thermal
      compromise to crewmembers, including cognitive and manual performance deficits.
      Revision of the flight rule governing crew actions during compromise of cabin
      thermal control has been undertaken to minimize thermal stress on returning
      Shuttle crewmembers. Modifications to the crew thermal protection system for the
      Shuttle are suggested.

PMID- 17511300
TI  - Cataract formation mechanisms and risk in aviation and space crews.
AB  - Induction of cataracts by occupational exposure in flight crew has been an
      important topic of interest in aerospace medicine over the past 5 yr, in
      association with numerous reports of flight-associated disease incidences. Due to
      numerous confounding variables, it has been difficult to determine whether there
      is increased cataract risk directly caused by interaction with the flight
      environment, specifically associated with added radiation exposure during flight.
      Military aviator records from the U.S. Air Force (USAF) and U.S. Navy (USN) and
      U.S. astronauts at NASA's Lyndon B. Johnson Space Center were evaluated for the
      presence, location, and age of diagnosis of cataracts. Military aviators with
      cataracts were found to have a younger average age at onset of their cataracts
      compared with astronauts with cataracts, however the prevalence of cataracts was
      found to be higher in astronauts than in military aviators. U.S. Air Force and
      U.S. Navy aviators' cataracts were most commonly located in the posterior
      subcapsular region of the lens while astronauts' cataracts were most likely to
      originate in the cortical zone. A prospective clinical trial which controls for
      confounding variables in examination technique, cataract classification, diet,
      exposure, and pharmacological intervention is needed to determine what percentage
      of the risk for cataracts is due to radiation, and how to best develop
      countermeasures to protect flight crews from radiation bioeffects in the future.

PMID- 17511301
TI  - Ionizing radiation-induced bioeffects in space and strategies to reduce cellular
      injury and carcinogenesis.
AB  - BACKGROUND: The bioeffects of space radiation on organisms outside of the
      environment of Earth's magnetosphere are a concern for long-duration exploration
      spaceflights. Potential mutagenic effects from space radiation exposure result
      from direct DNA damage or indirectly from the production of reactive oxygen
      species (ROS). HYPOTHESES: 1) Transepithelial electrical resistance (TER)
      measurements in cell culture monolayers may be used as a model system for
      detecting cell damage produced by exposure to simulated space radiation and for
      testing potential chemoprotective agents; 2) biomarkers of exposure that
      quantitate indirect radiation effects may allow prediction of cellular DNA
      damage; and 3) a multiple agent, chemoprevention cocktail may reduce the
      bioeffects of simulated space radiation. METHODS: Normal human and canine lung,
      breast, and renal epithelial cells were assayed in vitro and exposed to
      escalating doses of gamma or heavy-ion carbon (290 MeV/u), ceon (400 MeV/u), or
      iron (600 MeV/u) irradiation. Post-exposure measurements of TER, lipid
      peroxidation (LP) via measurement of 4-hydroxy-nonenal (4-HNE), and malonaldehyde
      (MDA) and assessment of chromosome damage via fluorescence in situ hybridization
      with tandem labeling of chromosome 1 were performed. RESULTS: Cells exposed to
      intermediate or high doses of radiation (5, 10, and 25 Gy) showed characteristic
      diminution in TER, thought to be secondary to dysfunction of tight junctions, and
      associated with membrane LP and other mechanisms. The cells also showed increases
      in 4-HNE + MDA measurements and increased frequency of chromosomal aberrations.
      Preliminary studies of cells incubated with media containing a combination of
      chemoprotective agents at the time of radiation exposure showed a 15-50%
      reduction in the radiation-induced changes in membrane resistance, levels of LP,
      and chromosomal aberrations relative to their unprotected cellular counterparts.
      CONCLUSION: TER measurement, in conjunction with measures of LP, may provide a
      useful model for determination of physiological changes caused by radiation
      exposure and the efficacy of chemoprotective agents. A multi-agent mixture of
      chemoprotective agents may be more effective than previously evaluated single
      agents alone.

PMID- 17511302
TI  - Biohazard potential of putative Martian organisms during missions to Mars.
AB  - Exploration Class missions to Mars will require precautions against potential
      contamination by any native microorganisms that may be incidentally pathogenic to
      humans. While the results of NASA's Viking biology experiments of the 1970s have
      been generally interpreted as inconclusive for surface organisms, and attributed
      to active but nonbiological chemistries, the possibility of native surface life
      has never been ruled out completely. It is possible that, prior to the first
      human landing on Mars, robotic craft and sample return missions will provide
      enough data to know with certainty whether future human landing sites harbor
      extant life forms. If native life were found to exist, it would be problematic to
      determine whether any of its species might present a medical danger to
      astronauts. Therefore, it will become necessary to assess empirically the risk
      that the planet contains pathogens based on terrestrial examples of pathogenicity
      and to take a reasonably cautious approach to biohazard protection. A survey of
      terrestrial pathogens was conducted with special emphasis on those whose
      evolution has not depended on the presence of animal hosts. The history of the
      development and implementation of Apollo anti-contamination protocol and
      recommendations of the National Research Council's Space Studies Board regarding
      Mars were reviewed. Organisms can emerge in Nature in the absence of indigenous
      animal hosts and both infectious and non-infectious human pathogens are therefore
      theoretically possible on Mars. Although remote, the prospect of Martian surface
      life, together with the existence of a diversity of routes by which pathogenicity
      has emerged on Earth, suggests that the probability of human pathogens on Mars,
      while low, is not zero. Still, since the discovery and study of Martian life can
      have long-term benefits for humanity, the risk that Martian life might include
      pathogens should not be an obstacle to human exploration. As a precaution, it is
      recommended that EVA (extravehicular activity) suits be decontaminated when
      astronauts enter surface habitats upon returning from field activity and that
      biosafety protocols approximating laboratory BSL 2 be developed for astronauts
      working in laboratories on the Martian surface. Quarantine of astronauts and
      Martian materials arriving on Earth should also be part of a human mission to
      Mars, and this and the surface biosafety program should be integral to human
      expeditions from the earliest stages of the mission planning.

PMID- 17511303
TI  - After the latest report from Medicare trustees, providers issue more calls for
      reform as they fear even harsher cuts to come.
AB  - The Medicare trustees' latest report prompted calls for reform on Capitol Hill.
      With the "45% trigger" activated, more cuts could be proposed. "Reform is needed
      and time is of the essence," says Treasury Secretary Henry Paulson, left. "The
      longer we delay, the larger the required adjustments will be, and the burden of
      making those adjustments will fall more heavily on future generations".

PMID- 17511304
TI  - Growth company growing doubt? Analysts wonder if Community Health is
      overestimating its purchase of Triad.

PMID- 17511305
TI  - Coverage bills hit the hill. Hospitals worried about Medicare expansion, payment.

PMID- 17511306
TI  - CFO suspended, Scrushy settles.

PMID- 17511307
TI  - Boom, boom, boom. Systems in Calif, Ill. and Kan. look to drum up new business
      with expansion!

PMID- 17511308
TI  - Cardinal Health digs deep. Company uses cash reserves to settle class-action
      suit.

PMID- 17511309
TI  - Show and tell. Joint Commission revelations in Boston.

PMID- 17511310
TI  - IT might be, IT could be, IT isn't.

PMID- 17511311
TI  - One hundred percent nonsense. Rule limiting growth of Medicare is a threat to
      providers, seniors.

PMID- 17511312
TI  - The price is right here. We're giving patients the kind of data available in any
      other consumer market.

PMID- 17511313
TI  - Creative license. As AHRQ struggles with flat funding levels, the agency has been
      forced to use novel approaches with its research grants.

PMID- 17511314
TI  - A psyched-up sector. As treatment approaches have changed in behavioral
      healthcare, so has facility design, leading to recent expansions, construction.

PMID- 17511315
TI  - Safety risk? Members seek info on residents' hours.

PMID- 17511316
TI  - A deadly mystery. A savage outbreak of Ebola virus is killing gorillas and
      chimps. Epidemiologists have just figured out why.

PMID- 17511317
TI  - Success at last. Couples fighting infertility might have more control than they
      think.

PMID- 17511318
TI  - A path to mental health.

PMID- 17511319
TI  - DoH to get the measure of PCTs working with the private sector.

PMID- 17511320
TI  - DoH names struggling acute trusts.

PMID- 17511321
TI  - Open or shut case as service shake-ups hinge on SNP result.

PMID- 17511322
TI  - On why tenders need loving care.

PMID- 17511323
TI  - Skills for a rosy future.

PMID- 17511324
TI  - Data briefing. New thinking on health variations.

PMID- 17511325
TI  - Mental health. Tales of the city.
AB  - Evidence suggests London has a higher proportion of serious mental illness than
      the rest of the country. Inpatient and community services are both under strain,
      and services for people with mild to moderate problems are particularly lacking.
      No single route exists to advertise all the organizations offering help.

PMID- 17511326
TI  - Data mangement. Shedding light on hidden activity.

PMID- 17511327
TI  - Older staff. Grey but not forgotten.

PMID- 17511328
TI  - Nursing workforce. Over 50, over here.

PMID- 17511329
TI  - Preserving patient autonomy and privacy in the era of genetic discoveries.

PMID- 17511330
TI  - Examining older adults' perceptions of health care providers: identifying
      important aspects of older adults' relationships with physicians and nurses.
AB  - This article describes older adults' conversations about their relationships with
      health care providers. Focus group participants (N = 23) were from three ethnic
      groups (Black, White, and Hispanic) and ages 53 to 92. All but three of the
      participants were women. Content analysis revealed an overarching theme of
      genuine caring and three sub-themes: interest in patients' well-being, respectful
      dialogue, and sharing of information. Older adults' perceptions of genuine caring
      by physicians and nurses did not differ by ethnicity. Older adults want to engage
      in a caring, respectful, and educational relationship with their health care
      providers, which is consistent with fundamental professional values.

PMID- 17511331
TI  - Improving depressive symptoms in community-dwelling older adults: a psychosocial
      intervention using life review and writing.
AB  - The purpose of this randomized, controlled trial was to test the efficacy of a
      community-based intervention, the Life Story Workshop, on depressive symptoms,
      operationalized as depression subscale scores on the Brief Symptom Inventory 18,
      in adults age 60 and older. Thirty-three men and women were randomly assigned to
      one of two groups: an intervention group that attended 2-hour workshops once a
      week for 10 weeks or a wait-list control group. The intervention provided an
      opportunity for older participants to reflect on, write, and share stories about
      their lived and current lives. The depression subscale of the Brief Symptom
      Inventory 18 was administered before and after the workshops. Mean depression
      scores were compared using Welch's t test. A significant improvement was measured
      for the intervention group compared with the control group (p = .03). This
      research supports the Life Story Workshop as an effective intervention for
      improving depressive symptoms in older adults.

PMID- 17511332
TI  - The circle of life: end-of-life care and death rituals for Hmong-American elders.
AB  - The Hmong are an ethnic minority from Southeast Asia who constitute a growing
      U.S. population. Gerontological nurses need to understand the cultural meaning
      and rituals associated with dying, death, and the bereavement process of Hmong
      Americans. Critical to this is the structure and role of clan and family as a
      source of support and their involvement in the decision-making process. In this
      article, we provide an overview of the traditional spiritual beliefs related to
      life and death with implications for end-of-life and postmortem care. Information
      was acquired through invited field experiences. Published literature and
      consultation with Hmong elders were used to clarify, enhance, and validate this
      understanding.

PMID- 17511333
TI  - Computer and internet access for long-term care residents: perceived benefits and
      barriers.
AB  - In this study, the authors examined residents' computer and Internet access, as
      well as benefits and barriers to access in nursing homes. Administrators of 64
      nursing homes in a national chain completed surveys. Fourteen percent of the
      nursing homes provided computers for residents to use, and 11% had Internet
      access. Some residents owned personal computers in their rooms. Administrators
      perceived the benefits of computer and Internet use for residents as facilitating
      direct communication with family and providing mental exercise, education, and
      enjoyment. Perceived barriers included cost and space for computer equipment and
      residents' cognitive and physical impairments. Implications of residents'
      computer activities were discussed for nursing care. Further research is
      warranted to examine therapeutic effects of computerized activities and their
      cost effectiveness.

PMID- 17511334
TI  - Assessing job satisfaction of nurse aides in nursing homes: the Nursing Home
      Nurse Aide Job Satisfaction Questionnaire.
AB  - In this study, the author examined the job satisfaction of nurse aides working in
      nursing homes using the Nursing Home Nurse Aide Job Satisfaction Questionnaire.
      The questionnaire consists of seven subscales and uses a visual analogue rating
      scale ranging from 1 (low score) to 10 (high score). The questionnaire was mailed
      to 2,872 nurse aides who were employed at 72 nursing homes located in 6 states. A
      total of 1,579 questionnaires were completed for a response rate of 55%. Mean
      subscale scores were: 7.8 for the work content subscale, 7.5 for the quality
      subscale, 6.9 for the training subscale, 6.8 for the coworkers subscale, 5.7 for
      the work demands subscale, 5.5 for the workload subscale, and 5.3 for the rewards
      subscale. Mean score for the global ratings was 7.4. The findings indicate that
      in general, nurse aides enjoy working with residents and their coworkers but are
      less satisfied with pay.

PMID- 17511335
TI  - Hormone therapy in perimenopausal and postmenopausal women: examining the
      evidence on cardiovascular disease risks.
AB  - Women may live for 30 years or longer after menopause with cardiovascular disease
      as their highest mortality risk. Menopause may correspond to health alterations
      for women, yet the use of estrogen during and after this transition has been
      controversial for the past four decades. The evidence from recent scientific
      studies does not support the use of hormone therapy for the prevention or
      treatment of cardiovascular disease, which has resulted in its removal from
      national guideline recommendations. However, because of concerns related to
      specific aspects of the research, there are gaps in the evidence. Studies are
      under way to evaluate alternate methods for hormone delivery, low-dose hormone
      therapy, and selective estrogen receptor modulators (SERMs) in reducing
      cardiovascular risks in perimenopausal and postmenopausal women. Implications for
      clinical nursing practice include education as well as assessment and counseling
      related to individual risk factors.

PMID- 17511336
TI  - DoH compiles hit-list of trusts that cannot survive under PbR.

PMID- 17511337
TI  - Payment by results. How crude tariffs are getting under the skin of specialists.

PMID- 17511338
TI  - On boards and barricades.

PMID- 17511339
TI  - Nursing chief is good and bad cop all in one. Interview by Oliver Evans.

PMID- 17511340
TI  - Barometer. Public health April 2007.

PMID- 17511341
TI  - The fall guys.
AB  - Violence against NHS staff is rife--one manager has been assaulted 15 times in 13
      years. NHS staff often lack confidence that their employer will take action if
      they are physically assaulted. The NHS should adopt a zero-tolerance approach,
      ensuring all incidents are reported to the police.

PMID- 17511342
TI  - Word on the wards.

PMID- 17511343
TI  - Is patient care paying the price?

PMID- 17511344
TI  - Changing for the better.

PMID- 17511345
TI  - Finding more time to care.

PMID- 17511346
TI  - Productive ward: the way forward.

PMID- 17511347
TI  - Community services. Take the strain from DVT care.

PMID- 17511348
TI  - Purification of Euphorbia characias latex peroxidase by calmodulin-affinity
      chromatography.
AB  - A new procedure to purify to homogeneity an Euphorbia characias latex peroxidase
      is performed employing a calmodulin-Sepharose column as affinity chromatography.
      The advantage of this approach is the isolation of a peroxidase under fast and
      mild elution conditions with a high recovery in total activity.

PMID- 17511349
TI  - Rat liver xanthine oxidoreductase: effect of adenine on the oxidase and
      dehydrogenase activities.
AB  - Xanthine oxidase (XO) and total oxidase plus dehydrogenase (XO+XDH) activities
      from rat liver were measured in the presence or absence of adenine in extracts
      prepared with or without DTT/PMSF in homogenization buffer. Presence of adenine
      in extracts, prepared with or without DTT/PMSF, caused a 45-60% decrease in XO
      and XO+XDH activities. Removal of adenine by dialysis from extracts prepared with
      or without DTT/PMSF resulted in the recovery of XO and XO+XDH activities to
      almost their pre-dialysis control levels. Enzyme activity after 24hr storage at 
      20 degrees C depended on the presence or absence of DTT/PMSF and adenine, with
      both XO and XO+XDH activities being lower in extracts with the combined presence
      of DTT/PMSF and adenine. Incubation of extracts at 37 degrees C for 30 minutes
      resulted in increased XO and XO+XDH activities, however, adenine-treated samples
      did not differ from their pre-incubation activities. The molecular mass of the
      enzyme from control and adenine-treated extracts was unchanged (300 kDa). Adenine
      treated extracts prepared with or without DTT/PMSF showed higher D/O ratios in
      all post-dialysis samples when compared with their pre-dialysis ratios. The
      results suggest that adenine may play a role in preventing the dehydrogenase to
      oxidase conversion during extract preparation, storage, overnight dialysis and
      heat treatment.

PMID- 17511350
TI  - Plasma levels of adrenomedullin and atrial natriuretic peptide in patients with
      congestive heart failure of various etiologies.
AB  - OBJECTIVE: The aim of this study was to evaluate the plasma levels of the
      adrenomedullin (ADM) and atrial natriuretic peptide (ANP) in adult and pediatric
      patients with congestive heart failure (CHF) of various etiologies and to
      investigate their relations with haemodynamic variables e.g. echocardiographic
      left ventricular ejection fraction (LVEF) and fractional shortening (FS).
      SUBJECTS AND METHODS: The study was made in 38 adult and 21 pediatric patients
      with CHF of various etiologies and compared with 15 adult and 10 pediatric normal
      healthy controls. Patients with CHF were classified according to the New York
      Heart Association (NYHA) functional classification into grades II to IV in adult
      patients and into grade IV in all pediatric patients. ADM and ANP plasma levels
      were determined prior to the treatment with enzyme immunoassay. RESULTS: A
      statistically significant difference in the plasma levels of ADM and ANP were
      found between pediatrics and adult patients and corresponding healthy controls.
      Their levels were progressively increased with severity of NYHA class in adult
      patients. We found a significant positive correlation between plasma levels of
      each of ADM and ANP and pulse rate, systolic and diastolic blood pressure; and a
      significant negative correlation between their plasma levels and
      echocardiographic LVEF and FS. A significant positive correlation between plasma
      levels of ADM and ANP in both pediatrics and adult patients were also found.
      CONCLUSION: Plasma levels of ADM and ANP increased in adult and pediatric
      patients with CHF irrespective of the cause. They were positively correlated with
      each other and negatively correlated with LVEF and FS. These findings might have
      important clinical implications in that a noninvasive blood test may be used to
      identify high-risk subjects for HF for more invasive procedures.

PMID- 17511351
TI  - Fenugreek seeds modulate 1,2-dimethylhydrazine-induced hepatic oxidative stress
      during colon carcinogenesis.
AB  - 1,2-dimethylhydrazine (DMH) is a colon carcinogen which undergoes oxidative
      metabolism in the liver. We have investigated the modulatory effect of fenugreek
      seeds (a spice) on colon tumor incidence as well as hepatic lipid peroxidation
      (LPO) and antioxidant status during DMH-induced colon carcinogenesis in male
      Wistar rats. In DMH treated rats, 100% colon tumor incidence was accompanied by
      enhanced LPO and a decrease in reduced glutathione (GSH) content as well as a
      fall in glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide
      dismutase (SOD) and catalase (CAT) activities. Inclusion of fenugreek seed powder
      in the diet of DMH treated rats reduced the colon tumor incidence to 16.6%,
      decreased the LPO and increased the activities of GPx, GST, SOD and CAT in the
      liver. We report that fenugreek modulates DMH-induced hepatic oxidative
      stressduring colon cancer

PMID- 17511352
TI  - Comparison of pistachio hull essential oils from different Tunisian localities.
AB  - Pistachio (Pistacia vera L.) fruit is well known for its oleaginous and edible
      seed. Less information is available about the hull constituted by the epicarp and
      the mesocarp. This part of the fruit contains an essential oil that can be
      valorized. Tunisia is one of the countries cultivating pistachio trees. This work
      presents essential oil composition of pistachio hulls (Mateur variety) from
      different geographical localities: Grombalia (North-East), Kairouan (Middle) and
      Sfax (Middle-East). Yields were more important in Sfax samples (0.53% on a dry
      weight basis). Alpha-terpinolene was the major compound for Grombalia fruits
      (35.7%), whereas Kairouan and Sfax samples where characterized by alpha-pinene
      (42.5 and 43.8% respectively). For all samples, monoterpene hydrocarbons
      predominated (more than 79.8% of the essential oil).

PMID- 17511353
TI  - Essential oil composition of Hypericum triquetrifolium Turra. aerial parts.
AB  - The essential oil obtained by hydrodistillation from the aerial parts of Tunisian
      endemic Hypericum triquetrifolium Turra (Clusiaceae) was analyzed using GC and GC
      MS. One hundred and nine compounds consisting of 92.2% of total detected
      constituents were identified. Sesquiterpene hydrocarbons were the main
      constituents (59.37%), Alpha-humulene, cis-calamenene, delta-cadinene,
      bicyclogermacrene, eremophilene, betacaryophyllene and (E)-gamma-bisabolene were
      found as the main ones. Alpha-pinene (10.33%) was detected as the main
      monoterpene hydrocarbons (12.19%). The oxygenated sesquiterpenes constituted
      (9.33%); caryophyllene oxide (1.38%) was reported as the main constituent of this
      fraction. The oxygenated monoterpenes were weakly represented (4.62%) and
      consisted of constituents in low percentages (<1%).

PMID- 17511354
TI  - Variations in the essential oil composition from different parts of Coriandrum
      sativum L. cultivated in Tunisia.
AB  - Essential oils obtained by hydrodistillation from different organs (flowers,
      leaves, stems and roots) of Tunisian coriander (Coriandrum sativum L.) was
      analyzed. GC and GC-MS analysis enabled us to identify 64 compounds and revealed
      great qualitative and quantitative differences between the analyzed parts. In all
      organs, the main compound was (E)-2-dodecenal, followed by (E)-2-tridecenal,
      gamma-cadinene, (Z)-myroxide, neryl acetate and eugenol. Multivariate analysis
      (PCA) revealed a high similarity in the essential oils composition between upper
      leaves and flowers in one hand and basal leaves, roots and stems on the other
      hand. Further, it has been reported an organ-dependant distribution of essential
      oil compounds.

PMID- 17511355
TI  - Effects of L-carnitine on RBC membrane composition and function in
      hyperinsulinemic rats.
AB  - The purpose of the study was to investigate the effects of L-carnitine (CA) on
      the susceptibility of erythrocyte (RBC) to peroxide-induced lipid oxidation, RBC
      membrane composition, ATPases activity and oxidative stress in fructose-fed
      hyperinsulinemic rats. The rats were subjected to experimental hyperinsulinemia
      and hyperglycemia by feeding a high fructose diet (60 g/100 g) for 6 weeks. The
      rats showed significant alterations in the RBC membrane composition. The protein
      content was lower than control animals, while cholesterol, phospholipids and free
      fatty acids were higher in fructose-fed animals. Significant differences in the
      total carbohydrate and relative proportions of hexose, hexosamine, sialic acid
      and fucose of membranes were observed. In these rats, membrane-bound ATPases
      (total ATPase, Na+, K+ ATPase, Mg2+ and Ca2+ ATPases) were significantly lower
      while thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides
      (LHP) in RBC membrane were significantly higher than those of control rats. The
      red cells were more susceptible to peroxide-induced oxidative stress that
      correlated with reduced levels of vitamin E found RBC membrane. When fructose
      diet fed rats were treated simultaneously with CA (300 mg/kg b.w/day, i.p.), such
      alterations in membrane composition and enzyme activities did not occur. Effects
      of fructose loading on lipid peroxidation was also alleviated by CA. These
      findings suggest that high levels of dietary fructose is detrimental to RBC
      membrane integrity and that CA may have membrane stabilizing effects in this diet
      induced model of type 2-diabetes.

PMID- 17511356
TI  - Articaine 4% with 1:200,000 epinephrine: an acceptable option for patients with
      long QT syndrome.

PMID- 17511357
TI  - Cone beam computed tomography.
AB  - CBCT has made a sizable impact on dentistry in recent years. Dentists are still
      developing uses for the CBCT in orthodontics, endodontics, oral surgery,
      periodontics, and restorative dentistry. These systems offer the many benefits of
      access, although all of them are very expensive. Each dental practice must
      evaluate the potential usage of the unit to make the purchase or lease cost
      effective.

PMID- 17511358
TI  - Core materials: when do you use them? What type is best?

PMID- 17511359
TI  - HIV and AIDs: update for dentistry.
AB  - The start of the AIDS pandemic was first recognized in the United States in 1981;
      however, the epidemic began in sub-Saharan Africa, a region that now accounts for
      more than two-thirds of the world's total infections. Since that time, more than
      67 million people have been infected and more than 25 million have died
      worldwide. This article reviews the current status of the epidemic in the U.S.
      and details the disease's impact on dentistry in this country as well as
      appropriate patient management.

PMID- 17511360
TI  - Attitudes and expectations of treating deep caries: a PEARL Network survey.
AB  - A survey was conducted within a practice-based dental research network to
      determine dentists' treatment methods for deep caries lesions and whether the
      dentists' intended treatment approaches were influenced by their expectations for
      pulpal exposure. The survey further examined how general dentistry practices have
      adopted scientific evidence of caries classification, excavation, and capping
      techniques. Dentists were queried regarding liner use, hypersensitivity
      considerations, point of endodontic therapy, and anticipated vitality outcomes
      from Class I resin-based composite restorations over three to five years. Of the
      93 practitioner-investigators who were in the network at the time of the survey,
      85 (92%) completed it. Of those who responded, 62% said that they would remove
      all caries when presented with a case in which one would expect pulpal exposure,
      while 18% would partially remove caries and 21% would initiate endodontic
      treatment; 17% reported that they would utilize an antimicrobial agent before a
      liner or bonding agent during restoration. The outcomes projected for tooth
      vitality over the next three to five years were equivalent regardless of the
      caries removal approach or the use of a liner/bonding agent. When beginning the
      preparation, the method of treatment did not change if a pulpal exposure was
      anticipated, other than a threefold increase in immediate endodontic treatment.
      When dentists were given a direct pulp cap scenario, the projected use of a
      liner/bonding agent changed little while the vitality projections decreased.
      Overall survey findings indicate that approximately 20% of network dentists favor
      partial caries removal techniques and that deep caries treatment outcome studies
      are warranted, given the various treatments employed.

PMID- 17511362
TI  - Oral periopathogens and systemic effects.
AB  - Management of oral biofilms allows dentists to help control the pathogens
      responsible for periodontal disease and decay. Increasing evidence indicates that
      the oral system is a portal for pathogenic microorganisms. This is a cumulative
      situation with systemic effects that can overcome an individual's resistance
      threshold, culminating in systemic sequela. New evidence indicates that
      controlling these oral pathogens has systemic benefits, as oral pathology is
      related to cardiovascular and respiratory disease, diabetes, and systemic
      inflammatory responses, as well as low birth weight and pre-term deliveries. Some
      insurance companies now cover periodontal scaling for gingivitis and periodontal
      disease for pregnant women and patients at risk for pregnancy.

PMID- 17511361
TI  - Evaluation of metal bond strength to dentin and enamel using different adhesives
      and surface treatments.
AB  - Because adherence of base metal alloys is important for the long-term clinical
      success of adhesive fixed partial dentures, it has been necessary to improve
      adhesion to metal substrate by using different surface treatments. This study
      used different surface conditioning methods and two different luting resins to
      evaluate the shear bond strength of base metal alloys to dentin and enamel. Sixty
      noncarious freshly extracted human teeth were mounted in a plastic holder filled
      with autopolymerized acrylic resin. After the roots were removed and 30 flat
      enamel and 30 flat dentin surfaces were exposed, the specimens were divided
      randomly into two main luting cement groups. Sixty nickel chromium (NiCr) metal
      specimens were fabricated and subjected to three different surface conditioning
      procedures: sandblasting with 50 microm aluminum oxide, tribochemical silica
      coating, and a combination of the two. Scanning electron mircoscopy (SEM)
      evaluations revealed mainly cohesive failures. Self-cure adhesive resulted in
      higher bond strengths to dental substrates. Higher bond strengths were achieved
      through a combination of sandblasting and tribochemical silica coating; however,
      further clinical research is required. A surface treatment that combines
      sandblasting with tribochemical silica coating can achieve a more effective bond
      for adhesive restorations with metal substrates.

PMID- 17511363
TI  - Size doesn't matter: needle gauge and injection pain.
AB  - Many dentists prefer using smaller gauge (27- or 30-gauge) needles for anesthesia
      injection, believing that needles with a smaller diameter result in less
      injection pain than wider diameter needles. For this study, three dentists in a
      general practice administered 930 injections to 810 adult patients using 25- and
      27-gauge needles for mandibular inferior alveolar block injections and 25-, 27-,
      and 30-gauge needles for maxillary buccal infiltration or palatal injections.
      Patients, who were blinded as to the needle gauge, were asked afterward to rate
      the injection pain on an 11-point scale (0-10). There was no statistically
      significant difference in perceived injection pain based on needle gauge when
      analyzed for injection location (mandibular, maxillary posterior, maxillary
      anterior, and palatal), injection side, patient gender, treating dentist, or
      overall. These results indicate that when it comes to injection pain and needle
      gauge, size does not matter.

PMID- 17511364
TI  - A correlation study of occlusal and pulp chamber anatomy: the maxillary first
      molar.
AB  - The success of endodontic therapy is based on a number of criteria, particularly
      the conservation of tooth structure. This principle requires a systematic
      approach to pulp chamber access. By correlating the occlusal anatomy with the
      location of the root canal orifice, a dentist may find a number of guidelines for
      improving access design. In this in vitro study, the authors evaluated 29 human
      maxillary first molars. Digital radiographs and digital occlusal photographs were
      taken of each specimen before and after decoronation at the cementoenamel
      junction (CEJ). The three images were superimposed on one another and evaluated
      for occlusal and pulpal patterns. The thickness of the pulp chamber walls of the
      CEJ varied, based on the circumference of individual teeth. In addition, the
      canal orifices at the pulp chamber floor exhibited a consistent pattern relative
      to the cusp tips, which may assist in access design.

PMID- 17511365
TI  - A correlation study of occlusal and pulp chamber anatomy: the mandibular first
      molar.
AB  - Many parameters must be addressed for endodontic therapy to succeed. Because
      conservation of tooth structure is vital, the pulp chamber and root canal
      orifices should be located by using a method that is consistent yet accurate. The
      correlation of occlusal anatomy with the locations of the root canal orifice may
      aid dentists with access design. This study sought to determine if a correlation
      existed between occlusal surface anatomy, pulp chamber location, and root canal
      orifice location. This in vitro study utilized 21 human mandibular first molars.
      For each specimen, amalgam restorations were placed in the respective cusp tips,
      with gutta-percha placed in each canal at the level of the furcation. The authors
      made digital radiographs and occlusal photographs of each complete specimen. The
      samples were sectioned horizontally at the level of the cementoenamel junction
      (CEJ). Using a digital software program, the radiographs were superimposed with
      the digital photographs and correlations of pulp chamber to locate the canal
      orifice and occlusal surface anatomy. The authors found that the pulp chamber of
      the mandibular first molar lies more lingual at the level of the CEJ. In
      addition, the orifices were consistent in their location relative to cusp tip
      anatomy, a discovery that may assist dentists with the access design.

PMID- 17511366
TI  - Mandible metastasis as the first sign from primary adenocarcinoma of the lung.
AB  - Adenocarcinoma of the lung that metastasizes to the mandible is very uncommon;
      only a few cases have been described in the English-language literature. This
      article presents a metastasis from adenocarcinoma of the lung affecting the
      mandible of a 64-year-old woman, in which the first discovered metastatic lesion
      was detected before the primary tumor. The immunoreactivity for human thyroid
      transcription factor-1 (TTF-1) in the oral lesion was essential for determining
      the site and type of the primary tumor, as the patient showed no clinical or
      radiographic evidence of a tumor in the thyroid gland. After the primary tumor in
      the lung was diagnosed, radiotherapy and chemotherapy were initiated;
      unfortunately, the patient died two months after the start of treatment. This
      article emphasizes the importance of a well-conducted examination for diagnosing
      metastatic oral lesions.

PMID- 17511367
TI  - Variations in rest vertical dimension: effects of standing posture in edentulous
      patients.
AB  - The orientation of a patient's head changes, depending on whether he or she is
      sitting or standing in a relaxed upright position. An edentulous patient's
      vertical dimension at rest may show variations that can result in an inaccurate
      determination of his or her occlusal vertical dimension. This study recorded the
      rest vertical dimension (RVD) established among 60 totally edentulous subjects
      who were standing in the position of greatest comfort (self-balance position) and
      compared it with the patients' RVD when they were seated in a relaxed upright
      position, with the Frankfort Plane parallel to the horizontal. The RVD was
      measured (in mm) between two dots located on the midline of the face. Two
      measurements were made: one when the patient was seated upright and relaxed (with
      the Frankfort Plane parallel to the horizontal) with no head support, and the
      other when the patient was standing relaxed on both feet in a self-balance
      position. Five alternated measurements were made for each subject in each
      position. A mean RVD was calculated for each subject in each body posture and the
      mean values from both positions were compared. Statistical analysis was performed
      using Student's t-test (alpha = 0.05). No significant differences were noted
      between the RVD of the seated and standing positions (P = 0.67).

PMID- 17511368
TI  - Case report: an unusually large epulis on the maxillary gingiva of a 24-year-old
      woman.
AB  - A 24-year-old woman had a red mass (2.4 x 1.4 cm) on her left maxillary gingiva
      (between teeth No. 11 and 12) that interfered with normal occlusion and speech.
      Although pyogenic granuloma was the clinical diagnosis, histopathologic
      examination revealed that the lesion was actually focal fibrous hyperplasia with
      focal mucinosis degeneration. This article illustrates the role of the oral and
      maxillofacial pathologist in establishing an accurate diagnosis of oral lesions
      and discusses the differential diagnosis of gingival enlargements.

PMID- 17511369
TI  - A case of Rocky Mountain spotted fever.
AB  - Rocky Mountain spotted fever is a serious, generalized infection that is spread
      to humans through the bite of infected ticks. It can be lethal but it is curable.
      The disease gets its name from the Rocky Mountain region where it was first
      identified in 1896. The fever is caused by the bacterium Rickettsia rickettsii
      and is maintained in nature in a complex life cycle involving ticks and mammals.
      Humans are considered to be accidental hosts and are not involved in the natural
      transmission cycle of this pathogen. The author examined a 47-year-old woman
      during a periodic recall appointment. The patient had no dental problems other
      than the need for routine prophylaxis but mentioned a recent problem with
      swelling of her extremities with an accompanying rash and general malaise and
      soreness in her neck region. Tests were conducted and a diagnosis of Rocky
      Mountain spotted fever was made.

PMID- 17511370
TI  - Drugs and the elderly patient.
AB  - The rational use of drugs in older persons is a challenging area of clinical
      practice. The increased incidence of multiple chronic illnesses contributes to
      disproportionately high use of prescription and over-the-counter (OTC)
      medications, which in turn leads to more adverse drug events among the elderly.
      Inadequate nutrition and poor patient compliance also may contribute to the
      problem. Drug studies that use young adult subjects cannot be extrapolated
      accurately to apply to the elderly because physiologic changes that occur with
      age affect the pharmacokinetics and pharmacodynamics of drugs. In addition,
      therapeutic target concentrations of drugs are impossible to define due to marked
      interindividual variation in the elderly population. Drugs should be administered
      to elderly patients only when absolutely necessary. The dosages should be
      titrated to a clearly defined clinical response and dentists should avoid drugs
      that are known to be problematic for older adults.

PMID- 17511371
TI  - Rotational path removable partial denture: an esthetic alternative.
AB  - Missing teeth can be replaced using any of a number of methods. Patients may
      choose to replace missing teeth with a prosthesis that is either removable,
      fixed, or retained with implants. When it is necessary to replace anterior or
      posterior teeth, a properly designed and fabricated rotational path removable
      partial denture can be both successful and esthetically pleasing to the patient.
      However, while a patient's functional and esthetic needs can be met successfully,
      rotational path removable partial dentures can be more demanding for the
      laboratory technician to fabricate and for the dentist to seat in the mouth.
      Rotational path removable partial dentures frequently are overlooked as a viable
      means of treating missing teeth. This article reviews the principles of
      rotational path removable partial dentures, as well as their categories,
      advantages, and disadvantages, in the hope that more dentists will consider them
      when the need arises.

PMID- 17511372
TI  - The human papilloma virus, the vaccines, and oral and oropharyngeal squamous cell
      carcinoma: what every dentist should know.
AB  - High-risk human papilloma virus (HPV) strains 16 and 18 have been shown to cause
      cervical cancer as well as other benign and malignant disorders. Oral and
      oropharyngeal squamous cell carcinoma (OOSCC) has been linked to high-risk HPV
      strains. Recent developments in the field of immunology have resulted in a
      vaccine to treat patients with HPV against cervical cancer. The widespread use of
      the HPV vaccine should reduce the risk of cervical cancer and could decrease the
      risk of OOSCC as well. This article examines the virus as well as the vaccines
      and how they could be used. A possible reduction in oral and oropharyngeal
      cancers as a result of widespread vaccination is discussed.

PMID- 17511373
TI  - White patch in the mucobuccal fold. Smokeless tobacco keratosis.

PMID- 17511374
TI  - Persistent diffuse white lesions in a child. White sponge nevus.

PMID- 17511375
TI  - [Image of the month. Epilepsy crisis and digital hippocratism ... pointing to the
      lungs].

PMID- 17511376
TI  - [How I treat...the dry skin of the hands].
AB  - Suffering from dry skin on the hands is a common feature in the general
      population. This condition is influenced by daily habits and occupational duties.
      It commonly corresponds to the expression of irritation dermatitis modulated by
      climatic and other environmental conditions. Other diseases including allergic
      contact dermatitis, psoriasis and dermatomycosis can also be responsible for a
      similar clinical presentation. In the common discrete irritative type, a
      specifically designed cosmetic product may considerably improve the discomfort
      experienced by the patient. By contrast, the efficacy of most barrier creams
      remains unconfirmed. The chronic use of topical corticosteroids can lead to
      dependency and to progressive cutaneous atrophy.

PMID- 17511377
TI  - [Clinical case of the month. Pulsus alternans: a rare semiologic sign of severe
      left ventricular dysfunction].
AB  - A paradigmatic case of pulsus alternans observed during exploration of a severe
      aortic valve disease is reported. Pulsus alternans is a rare semiologic sign of
      severe left ventricular dysfunction and the mechanisms of its appearance are
      discussed.

PMID- 17511378
TI  - [Clinical case of the month. Hepatitis B reactivation in an Ag HBs negative
      patient].
AB  - A 66-year-old man, Ag HBs negative, suffering from glomerulonephritis was treated
      with prednisone. Hepatitis B reactivation was observed after increasing and
      regression of corticotherapy. Pathogenesis, efficient therapy and prevention of
      reactivation of hepatitis B will be reviewed.

PMID- 17511379
TI  - [Clinical case of the month. Miller-Dieker (lissencephaly) syndrome].
AB  - We present the case of a 10-year-old boy who presents with a severe epilepsy
      resistant to medical treatment in the context of a Miller-Dieker syndrome. This
      patient underwent the implantation of a pneumogastric nerve stimulator. We
      describe the patient's clinical history and the main characteristics of
      lissencephaly syndrome.

PMID- 17511381
TI  - [Strategies to shorten the time from urgent admission to coronary angioplasty: a
      recent publication in the New England Journal of Medicine].
AB  - A recent publication in New England Journal of Medicine stresses the fact that
      the mere presence of a coronarography equipment to dilate acute myocardial
      infarction is not sufficient to obtain the opening of the related myocardial
      infarction artery in due time.

PMID- 17511380
TI  - [Perforation of a hiatal hernia after a high altitude flight].
AB  - We report the case of a 84-year-old patient who came to the emergency department
      for vomiting and epigastralgia which had occurred during an air flight. These
      symptoms were related to the intraabdominal perforation of a massive hiatal
      hernia on barotrauma due to high altitude.

PMID- 17511382
TI  - [Anogenital condylomata in the children. Practice guidelines for a medical
      expertise].
AB  - Belgium has been confronted to cases of paedophilia for years. It seems adequate
      to suggest some guidelines in cases of a child or a teenager diagnosed with ano
      genital warts during a consultation. They are not always the consequence of
      sexual abuse. Three contaminations are possible: ante natal and peri natal (in
      utero or during delivery), by direct contact (auto or hetero inoculation),
      through sexual contact. This trusted practitioners to handle this unusual
      situation from the child protection, to multidisciplinary management and judicial
      prosecution against suspect. When using some different way to know what kind of
      HPV type; it's possible to give some information about transmission and it's
      possible to do confrontations with the results of the lesions' suspect. It is
      also interesting to identify very highs oncogenic potential HPV for the survey's
      patient. Finally the most important is to know that the most recurrences result
      into reactivations from infra-clinically infections and are not new
      contaminations. It is important do not drop a new suspicion through hypothetic
      contaminator.

PMID- 17511383
TI  - [Hutchinson-Gilford progeria syndrome: clinical and molecular analysis in an
      African patient].
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disease
      characterized by an early onset of several clinical features including premature
      ageing in children. Approximately 80% of HGPS cases are caused by a de novo
      single-base pair substitution c.1824 C>T (GGC > GGT, p.Gly608Gly) within the exon
      11 of the LMNA gene which codes for lamins A and C proteins. This mutation
      creates an abnormal splice donor site, leading to the formation of a truncated
      lamin A protein. Only a very few cases of African patients with HGPS have been
      reported, but none of them has been characterized at the molecular level. We
      report here a 12 year-old-girl African patient with HGPS, in whom the p.Gly608Gly
      heterozygous disease-causing mutation was found.

PMID- 17511384
TI  - [Evaluation of the bacteriologic quality of breast milk in a neonatology service
      in Belgium].
AB  - Many studies demonstrated that human milk is the recommended source of enteral
      nutrition in preterm infants providing several benefits with regards to feeding
      tolerance, immunity and cognitive development However, neurological immaturity
      and associated clinical conditions prevent them from suckling effectively.
      Therefore, mother's milk must be expressed, stored and transported to the
      neonatal unit and could be contaminated. The microbiological quality of human
      milk was evaluated on each donation to the neonatal intensive care unit of the
      University of Liege, Belgium from November 1, 2003 to January 31, 2005. In all,
      5842 samples from 176 mothers were included in the study. Samples were classified
      according to the exclusive presence of coagulase negative Staphylococcus and
      their number (less or more than 104 germs per ml) or to contamination with
      pathogens. More than 50% of analyzed milks had to be pasteurized (46%; >104
      coagulase negative Staphylococcus per ml) or to be discarded (7% pathogen
      contamination). The incidence of pasteurisation tends to increase during the
      summer, suggesting a seasonal influence. Maternal profiles were established
      longitudinally. Among the 60 mothers whose at least one sample had pathogen
      contamination, 27% had a contamination occurring only during a few days, but 73%
      had more than 50% of their samples discarded. This study suggest the need to
      promote the use and the financial support of intrahospital human milk bank units
      to support the safe use of raw and pasteurised human milk in preterm infants.

PMID- 17511385
TI  - [Cancer associated retinopathy (CAR). Two clinical cases and review of the
      literature].
AB  - The cancer associated retinopathy (CAR) is a paraneoplasic retinopathy in which
      an antigen-antibody reaction, due to retinal antigens, also expressed in tumours,
      leads to degeneration of retinal photoreceptor cells. We observed in CHL
      Luxembourg, 2 clinical cases of non-Hodgkin's lymphoma with severe prognosis in
      whom we described the presence of anti-recoverin antibodies. The CAR is most
      frequently associated with small cell lung and ovarian carcinomas. Clinical
      symptoms (phosphenes, progressive loss of eyesight) sometimes, occur before the
      diagnostics of primary cancer. Retinal degeneration may be assessed by
      electroretinogram, visual field, fundus oculi. A crossed reactivity between
      tumour and retinal antigens may initiate an antigen-antibody reaction, that
      implicates optic lesions. Different antigenic proteins have been evidenced, the
      most frequent being the recoverin. This protein plays a role in the adaptation to
      light and darkness. It is expressed in more than 50% of different types of
      neoplastic cells and would play a role in tumour proliferation. The antigen
      antibody reaction leads to death by apoptosis of photoreceptor and bipolar
      retinal cells. These antirecoverin antibodies are also observed in other retinal
      degenerative diseases. The diagnosis is confirmed by titration of antibodies in
      the serum by Western Blot, Elisa and immunohistochemical methods. However, this
      diagnosis is by exclusion (vs. brain metastasis, drug toxicity, demyelinating
      diseases, autoimmune non paraneoplastic retinopathies). Corticosteroids are the
      only therapy that can bring some benefit. There is no value in starting a therapy
      if the retinal degeneration has reached an advanced stage. Note that the CAR must
      be distinguished from the Melanoma Associated Retinopathy (MAR) which is a
      similar paraneoplastic syndrome, but with rapid evolution of its symptoms and
      different etio-pathogenesis.

PMID- 17511386
TI  - [How I explore...the revisited toxic path of scleroderma].
AB  - The name scleroderma is given to a spectrum of diseases which differ clinically
      and bear different prognostic risks. The origins of the various forms of the
      disease are unclear. A toxic influence has been suggested, particularly for the
      progressive systemic scleroderma. However, the imputability of the suspected
      chemicals often remains unsettled.

PMID- 17511387
TI  - [Medication of the month. Olmesartan medoxomil hydroclorothiazide (Olmetec Plus
      or Belsar Plus].
AB  - The therapeutic control of hypertension is still a global challenge and
      frequently requires combination therapy. Olmesartan medoxomil hydrochlorothiazide
      (Olmetec plus, Belsar plus) is a fixed-dose combination of olmesartan 20 mg and
      hydrochlorothiazide 12.5 or 25 mg. Olmesartan is a well known angiotensin II AT1
      receptor blocker characterized by a good efficacy, a fast and prolonged duration
      of action and a placebo-like tolerability. With the combination therapy, no
      significant change of pharmacokinetics of either component is observed. The fixed
      dose combination results in a greater blood pressure reduction compared to
      monotherapy with either component. This is at least effective as or even more
      effective than the combination of atenolol or losartan with hydrochlorothiazide,
      respectively. The responder rate is about 90%. The safety and tolerability remain
      excellent. Beyond the antihypertensive effect, olmesartan significantly reduces
      vascular inflammation and the wall-to-lumen ration in arteries. The starting dose
      is 20/12.5 mg.

PMID- 17511388
TI  - [On the way to enlightenment].

PMID- 17511389
TI  - [Using the video-telephone for direct connections].

PMID- 17511390
TI  - [Bringing back professional autonomy].

PMID- 17511391
TI  - [The translator is at the telephone].

PMID- 17511392
TI  - [A magnificent European building site].

PMID- 17511393
TI  - [Togetherness or concurrence?].

PMID- 17511394
TI  - [Health--an enormous development in China].

PMID- 17511395
TI  - [In the middle of confusion].

PMID- 17511396
TI  - [Fortunate nursing planning--in motion].

PMID- 17511397
TI  - [We want to give cancer patients a perspective].

PMID- 17511398
TI  - [Wait, wait a while].

PMID- 17511399
TI  - [Greetings, , I am your cyber-nurse].

PMID- 17511400
TI  - [When words are not enough].

PMID- 17511401
TI  - [The empty talk of competence, the guarantee of quality].

PMID- 17511402
TI  - [An answer to the emotional blessings of life].

PMID- 17511403
TI  - [Be aware of insidious messages from the brain].

PMID- 17511404
TI  - [A net...of support].

PMID- 17511405
TI  - The Bulgarian Health Care Reform and Health Act 2004.
AB  - Since 1997 post-communist Bulgaria has started structural and financial Health
      Care reform. The reform's framework is laid down by new health legislation. The
      main law regulating the broad framework of the health system is the Bulgarian
      Health Act (BHA) 2004 which came into force in January 2005. The aim of this
      paper is to introduce and analyze the main features of the Bulgarian Health Care
      Reform and Health Care Act 2004. Key issues in BHA include: organization and
      financing of health care; health protection; health promotion, patients' rights,
      accessibility and quality of health care, mental health, alternative medical
      services, medical education, medical profession and medical science, and
      administrative-punitive measures. BHA is a policy document justifying that
      Bulgaria is prepared and willing to meet the challenge to bring the health status
      of the Bulgarian population to the current average European health level, as well
      as that in the EU Member States.

PMID- 17511406
TI  - Personal reflections of a tribunal member--the interface between medical practice
      and legal decision making in guardianship.
AB  - Tribunals are often constituted by members of the legal profession. Sometimes
      members are appointed because of specific expertise in a certain area. The area
      of guardianship, being a protective jurisdiction, has aspects that make it
      different from other areas often dealt with by tribunals. Interpersonal skills
      for tribunal members are important, as well as an understanding of the health
      system. Being both a tribunal member and a medical practitioner brings a unique
      experience to practice as a doctor but also to practice as part of a tribunal. It
      raises some dilemmas as well. This paper gives a brief outline of the role of the
      Guardianship List of the Victorian Civil and Administrative Tribunal in
      Australia. It discusses the experience of a Tribunal member, from a decision
      making perspective and a professional expertise perspective, resulting in an
      ultimately unique picture that assists in achieving a necessary outcome for the
      benefit of the person in need of assistance.

PMID- 17511407
TI  - Practical aspects of the issue of patients refusing medical care.
AB  - The issue of patients refusing medical care is one of the most difficult and
      complicated in the medicolegal world, and involves moral and philosophical
      questions in addition to medical and legal ones. Article 13 (A) of the Israeli
      Patient Rights Law of 1996 (hereinafter: "the Patient Rights Law") emphasizes the
      autonomy of the patient over his body and explicitly states that "No medical care
      will be given to a patient unless informed consent is given by him..." Article 13
      (B) (4) of the Patient Rights Law states that obtaining informed consent requires
      the caregiver to give the patient the medical information required to a
      reasonable extent to allow the patient to decide whether to agree to the proposed
      care, including information on the odds and risks of alternate medical
      treatments. It is important to clarify, however, that the patient's right to give
      or withhold informed consent to medical care, does not grant him under any
      circumstances a right to dictate to the caregiver to use medical methods that are
      unconventional or that are not medically indicated, thus violating the known
      edict: primum non nocere (first, do no harm). This paper provides some case
      studies and discussion of illustrative situations.

PMID- 17511408
TI  - Judicial considerations with regard to civil liability.
AB  - This paper addresses the relationship between the doctrinaire position of a judge
      in terms of the civil liability objective and subjective theories and the results
      of their decisions in terms of "acquittal/against judgments". A system of
      classification of matter of fact results is proposed and the influence on the
      result of the decision of each category is also tested. The material consists of
      71 records of judicial procedures from Sao Paulo State Court of Justice.

PMID- 17511409
TI  - Communalization of health care: how to do it properly. Criteria for a just
      communalization of health care applied to the Dutch situation.
AB  - Communalization of health care refers to the increasing responsibility of
      citizens to look after their ill or handicapped fellow members of society and to
      provide care to them. Governments in Western Europe more and more develop health
      care policies directed at communalization of health care. The article discusses
      the care responsibilities of individuals based on the views of the philosophers
      Buber, Levinas, and Ricoeur and on the views of the family therapist Nagy. The
      care responsibilities of states are discussed in terms of the views of the
      political philosophers Rawls and Daniels and these are linked to right liberal,
      left liberal, and Christian-democrat views on care responsibilities of states.
      Thereupon, four criteria for a proper communalization of health care are proposed
      and different forms of health care policies with respect to communalization of
      care are assessed. In the last section, we look closely at several measures in
      the just reformed Dutch health care system and discuss how far these measures
      meet our criteria for a proper communalization. We focus in this section on the
      effects of these measures on family care because more and more family care plays
      an important role in good functioning of the health care system.

PMID- 17511410
TI  - Legal implications of public health guidelines.
AB  - Medical guidelines aim to provide stylised procedures to manage illnesses.
      Doctors might believe that conforming to guidelines provides protection within
      legal proceedings. Guidelines were deemed inadmissible evidence in Regina v Ross
      Gillett, raising some concerns. Gillett was a middle aged man who denied having
      epilepsy when applying for a driver's licence and was involved in a car crash
      which killed three people. He had confirmed epilepsy yet expert witnesses
      testified he was within AUSTROADS Guidelines for fitness to drive. The judge
      refused to admit these Guidelines into evidence, finding the defendant guilty of
      dangerous driving occasioning death. The Guidelines were endorsed by all
      Australian and New Zealand traffic authorities, seven medical colleges, two sub
      specialty faculties, seventeen illness-related organisations plus the Australian
      Medical Association. Their purpose was to achieve "...best practice for the safe
      and effective management and use of the road system...". The judge rejected them
      when considering his verdict. Precedence demands the judiciary consider all
      relevant data although the Guidelines were deemed irrelevant and could not be
      admitted into evidence. Guidelines cannot bind the court unless enforced by
      legislation. It is difficult for doctors to comprehend how Guidelines, designed
      to determine optimal road usage, can be excluded when analysing a road accident.
      Doctors need to be circumspect about applying Guidelines in the wake of Gillett.

PMID- 17511411
TI  - Patient rights protection in the Czech Republic: challenges of a transition from
      Communism to a modern legal system.
AB  - The post-Communist countries in Central Europe, including the Czech Republic,
      underwent a rapid transformation of their legal systems, within which the concept
      of patient rights passed through revolutionary changes. This process however
      often left significant gaps in patient rights protection. There are practical
      difficulties for patients in defending their rights before the courts, such as
      problems with obtaining evidence and independent expert opinions, long delays and
      high costs of court proceedings, strict burden of proof rules and low
      compensation levels. Modern patient rights often collide with the systems of
      health care provision that are still unprepared for patient autonomy and
      responsibility. The experience gained in the transition process might be
      applicable also to other countries that undergo changes from traditional to
      modern system of patient rights protection.

PMID- 17511412
TI  - Ethical problems related to information and pharmaceutical care in Spain.
AB  - This paper represents a reflection on the limits and objectives of the
      information pharmacists should offer in pharmacies. The obligation of a
      pharmacist to follow the patient's therapeutic progress makes it necessary to
      integrate this figure into an ethical-legal framework and to define the objective
      of the health-related information offered, taking into account the patient's
      welfare and constitutional rights.

PMID- 17511413
TI  - Treatment or crime? The status of stem cell therapies and research in South
      African law.
AB  - The author develops a thorough analysis of current and proposed South African law
      in relation to the harvesting and use of stem cells. He begins with the question
      of ownership of the umbilical cord at birth and afterwards. The problems of
      informed consent in these situations are discussed. Changes in the law in South
      Africa, now in progress, should ameliorate some of the difficulties.

PMID- 17511414
TI  - France and the United States: the legal and ethical differences in assisted
      reproductive technology (ART).
AB  - In this paper, we will look at the development and the current status of the laws
      in France (and to some extent other EU nations) and the United States. In doing
      so, many differences will emerge about the views and values of assisted
      reproductive technology in the two countries. We will try to articulate some of
      those underlying moral, political, and legal differences.

PMID- 17511415
TI  - Anonymity in connection with sperm donation.
AB  - Since Sweden abolished anonymity in connection with sperm donation in 1985, a
      number of other countries have followed suit. A legal provision still exists in
      Denmark to the effect that the donor must be anonymous. Arguments given in a
      Danish context against retaining the present scheme involving anonymous sperm
      donation will be discussed. The biggest problem with sperm donation seems to be
      non-disclosure. Current and important arguments in favour ofabolishing anonymity
      are that it sends out a clear signal that non-disclosure is unacceptable and
      that, in principle, all citizens should have access to the information available
      about themselves. However, the arguments can be criticised both from theoretical
      (legal) and several practical (medical) points of view. A substantive alternative
      to abolishing anonymity might be to inform parents about avoiding non-disclosure-
      and to design information material for the children, to support the parents.

PMID- 17511416
TI  - Ten years hence--has the South African choice on Termination of Pregnancy Act,
      Act 92 of 1996, realised its aims? A moral-critical evaluation.
AB  - The South African Choice on Termination of Pregnancy Act (Act 92 of 1996) (CTOP)
      passed by parliament ten years ago, aims to promote female reproductive autonomy
      through legitimising free access to abortion up to 20 weeks' of gestation. The
      article critically evaluates CTOP and highlights three societal concerns: the
      effect of CTOP on the self-esteem of nurses who perform abortion; the effect on
      general societal morality, and its desirability. CTOP has enjoyed mixed success.
      On the plus side, it has furthered female reproductive autonomy, has decreased
      early pregnancy maternal mortality and has advanced non-racialism through equal
      access to safe abortion. On the minus side, it remains controversial; the
      majority of the population opposes abortion on request, predominantly based on
      religiously-informed intuitions on the value of ante-natal life. Officials and
      managers of public health care facilities are often obstructive, and TOP
      personnel victimised and socially stigmatised. An unacceptably high rate of
      unsafe abortion prevails, particularly in rural areas and amongst adolescents,
      but also in certain urban areas. The prime causes are inadequate public
      education, attitudinal problems, and lack of psychological support for TOP
      personnel, the segregation of ante-natal care and abortion services, inadequate
      training, research, communication and contraceptive services, absence of
      incentives for TOP personnel and "traditional" gender roles and male power-based
      domination in reproductive choices. Corrective measures include a goal directed
      educational programme and initiatives like value clarification workshops which
      have been effective in changing negative attitudes of participants, and may thus
      address stigmatisation, improve working conditions of TOP personnel, promote
      societal tolerance and acceptance, and informed consent. Of particular concern
      are the questions of informed consent, minors, promotion of counselling and
      contraceptive services (particularly for adolescents), conscientious objection
      and the protection of compliant (and non-compliant) personnel.

PMID- 17511417
TI  - Presumed consent in the law of the Russian Federation on transplanting organs.
AB  - In this article, the author defines and discusses various concepts of consent in
      relation to organ transplantation. Beginning with the law of the Russian
      Federation, he highlights the benefits and shortcomings of basic provisions and
      parameters of consent in Russian law. The situation is some other countries is
      reviewed from a comparative aspect. With the object of making transplantation
      more widespread, liberal interpretations of the rules are to be encouraged.

PMID- 17511418
TI  - Involuntary psychiatric hospitalization.

PMID- 17511419
TI  - Scanning electroporation of selected areas of adherent cell cultures.
AB  - We present a computer-controlled scanning electroporation method. Adherent cells
      are electroporated using an electrolyte-filled capillary in contact with an
      electrode. The capillary can be scanned over a cell culture and locally deliver
      both an electric field and an electroporation agent to the target area without
      affecting surrounding cells. The instantaneous size of the targeted area is
      determined by the dimensions of the capillary. The size and shape of the total
      electroporated area are defined by these dimensions in combination with the
      scanning pattern. For example, striped and serpentine patterns of electroporated
      cells in confluent cultures can be formed. As it is easy to switch between
      different electroporation agents, the method is suitable for design of cell
      cultures with complex composition. Finite element method simulations were used to
      study the spatial distributions of the electric field and the concentration of an
      electroporation agent, as well as the fluid dynamics related to scanning and flow
      of electroporation agent from the capillary. The method was validated for
      transfection by introduction of a 9-base-pair-long randomized oligonucleotide
      into PC12 cells and a pmaxGFP plasmid coding for green fluorescent protein into
      CHO and WSS cells.

PMID- 17511420
TI  - Spectroscopic probing of dynamic changes during stimulation and cell remodeling
      in the single cardiac myocyte.
AB  - Optical microscopy, involving both fluorescence imaging and confocal Raman
      microspectroscopy, was used to visualize single, isolated, electrically active
      heart muscle cells. For example, short-term, dynamic changes in Raman bands
      during the contraction cycle, as well as persistent band changes during
      structural remodeling (microscopic rearrangements of cellular structures) in
      culture over longer periods of time, were obtained from the cellular content
      (sarcoplasm) of the heart cells. The results of the short-term studies, collected
      during electrical stimulation, showed dynamic changes in the Raman amide I band
      intensity, which occurred in phase with changes in cell length during
      cardiomyocyte contraction. The longer term studies of quiescent cardiomyocytes in
      culture over 3 days revealed a progressive and sustained increase in the
      intensity of the amide I band. Over the same period of culture, a decrease in the
      number of t-tubules (invaginations of the cell membrane, sarcolemma, which ensure
      the spreading of the action potential into the bulk of the sarcoplasm) was
      observed using confocal z-sections of the fluorescently labeled sarcolemma. The
      ability to measure both short-term dynamic changes associated with stimulated
      contraction and longer term persistent remodeling in the structure of
      intracellular macromolecules is valuable for assessing the physiological state of
      the cell, in real time.

PMID- 17511421
TI  - Dynamic range and mass accuracy of wide-scan direct infusion nanoelectrospray
      fourier transform ion cyclotron resonance mass spectrometry-based metabolomics
      increased by the spectral stitching method.
AB  - Direct infusion nanoelectrospray Fourier transform ion cyclotron resonance mass
      spectrometry (DI nESI FT-ICR MS) offers high mass accuracy and resolution for
      analyzing complex metabolite mixtures. High dynamic range across a wide mass
      range, however, can only be achieved at the expense of mass accuracy, since the
      large numbers of ions entering the ICR detector induce adverse space-charge
      effects. Here we report an optimized strategy for wide-scan DI nESI FT-ICR MS
      that increases dynamic range but maintains high mass accuracy. It comprises the
      collection of multiple adjacent selected ion monitoring (SIM) windows that are
      stitched together using novel algorithms. The final SIM-stitching method, derived
      from several optimization experiments, comprises 21 adjoining SIM windows each of
      width m/z 30 (from m/z 70 to 500; adjacent windows overlap by m/z 10) with an
      automated gain control (AGC) target of 1 x 10(5) charges. SIM-stitching and wide
      scan range (WSR; Thermo Electron) were compared using a defined standard to
      assess mass accuracy and a liver extract to assess peak count and dynamic range.
      SIM-stitching decreased the maximum mass error by 1.3- and 4.3-fold, and
      increased the peak count by 5.3- and 1.8-fold, versus WSR (AGC targets of 1 x
      10(5) and 5 x 10(5), respectively). SIM-stitching achieved an rms mass error of
      0.18 ppm and detected over 3000 peaks in liver extract. This novel approach
      increases metabolome coverage, has very high mass accuracy, and at 5.5 min/sample
      is conducive for high-throughput metabolomics.

PMID- 17511423
TI  - Aptamer-based enantioselective competitive binding assay for the trace enantiomer
      detection.
AB  - The development of highly enantioselective assays and sensors has received much
      attention for the determination of enantiomeric impurities at a low level. For
      chiral compounds, the efficient monitoring of the in selection procedure has
      allowed the isolation of nucleic acid aptamers which are able to strongly
      discriminate the target enantiomers. In this paper, we demonstrated for the first
      time that an aptamer can be successfully used to design a highly enantioselective
      tool for the trace enantiomer detection. The aptamer-based stereoselective assay
      was developed using an affinity capillary electrophoresis-based competitive,
      homogeneous format and an on-capillary mixing approach. Detection of as low as
      0.01% of the minor enantiomer in a nonracemic mixture can be achieved, in a short
      analysis time (<5 min).

PMID- 17511422
TI  - Development of a monoclonal antibody-based broad-specificity ELISA for
      fluoroquinolone antibiotics in foods and molecular modeling studies of cross
      reactive compounds.
AB  - A competitive indirect enzyme-linked immunosorbent assay (ciELISA) using
      monoclonal antibodies (Mabs) having broad specificity for fluoroquinolone (FQ)
      antibiotics is described. Four FQs, ciprofloxacin (CIP), enrofloxacin (ENR),
      norfloxacin (NOR), and ofloxacin (OFL), were conjugated to bovine serum albumin
      for immunogens and to ovalbumin for coating antigens. A Mab C4A9H1 raised against
      the CIP hapten exhibited high cross-reactivity (35-100%) with 12 of 14 FQs and
      detected these FQs in a ciELISA below their maximum residue levels (MRLs) with
      good sensitivity at 50% binding inhibition (IC50). The quantitative structure
      activity relationship (QSAR) between Mab C4A9H1 and various FQs by comparative
      molecular field analysis (CoMFA) showed a high predictive ability with a cross
      validation q2 value of 0.866. Using a simple purification process and the broad
      specificity ciELISA adapted for analysis of FQs in chicken muscle, chicken liver,
      honey, shrimp, and whole egg samples demonstrated recoveries of 60-93% for CIP,
      ENR, NOR, OFL, flumequine, and danofloxacin.

PMID- 17511424
TI  - Detection of malaria infection via latex agglutination assay.
AB  - A rapid test for malaria diagnosis based on specific agglutination of sensitive
      polystyrene particles containing carboxylic acid with antigen or antibody
      molecules in the presence of their corresponding antibody or antigen in human
      plasma has been achieved. The particle-malaria antigen conjugate (PAgC), particle
      monoclonal IgG antibody to Plasmodium falciparum heat shock protein 70 conjugate
      (PmAbC), and particle-polyclonal IgG antibody to P. falciparum malaria conjugate
      (PpAbC) were prepared via adsorption process. The higher affinity of the malaria
      antigen adsorption onto particles was observed compared to that of the
      antibodies. Immunoagglutination of sensitive latex particles was monitored by
      measuring the change in turbidity, and the aggregate's formation was clearly
      observed under optical microscope. The efficacy in malaria diagnosis of the
      conjugated particles evaluated at an outpatient malaria clinic (Mae Sod,
      Thailand) indicated a success detection of antibody or antigen. Sensitivity of
      PAgC, PmAbC, and PpAbC for P. falciparum was 84%, 90%, and 90%, respectively,
      while specificity for malaria disease was 70% for PAgC and 80% for PmAbC and
      PpAbC. The rapid agglutination-based latex particles assay developed herein
      showed a great potential for diagnosis of malaria infection.

PMID- 17511425
TI  - Pharmaceuticals and related drugs.

PMID- 17511426
TI  - The conformers of hydroxyacetaldehyde.
AB  - Both two and eighteen dimensional quantum diffusion Monte Carlo (DMC)
      calculations were used to study the isomers of hydroxyacetaldehyde. A total of
      four unique minima, and the transition states connecting them, were located. Both
      two and eighteen dimensional potential energy surfaces were generated and used in
      the DMC runs. The rotational constants for the global minimum were predicted for
      all experimentally identified isotopomers and an approximate equilibrium
      structure obtained by combining our theoretical results with the experimentally
      observed rotational constants. The results obtained for the remaining isomers
      indicate that not all of them can be isolated in the gas phase.

PMID- 17511427
TI  - New diagnostic of the most populated conformer of tetrahydrofuran in the gas
      phase.
AB  - The most populated conformer of tetrahydrofuran (C(4)H(8)O) has been diagnosed as
      the Cs conformer in the present study, jointly using experimental electron
      momentum spectroscopy (EMS) and quantum mechanics. Our B3LYP/6-311++G** model
      indicates that the C1 conformation, which is one of the three possible
      conformations of tetrahydrofuran produced by pseudorotation in the gas phase, is
      a transition state due to its imaginary frequencies, in agreement with the
      prediction from a recent ab initio MP2/aug-cc-pVTZ study (J. Chem. Phys. 2005,
      122, 204303). The study has identified the fingerprint of the highest occupied
      molecular orbital (HOMO) of the C(s) (12a') conformer as the most populated
      conformer. The identification of the C(s) structure, therefore, leads to the
      orbital-based assignment of the ionization binding energy spectra of
      tetrahydrofuran for the first time, on the basis of the outer valence Green
      function OVGF/6-31G* model and the density functional theory (DFT) SAOP/ET-PVQZ
      model. The present study explores an innovative approach to study molecular
      stabilities. It also indicates that energetic properties are not always the most
      appropriate means to study conformer-rich biological systems.

PMID- 17511428
TI  - Solvation dynamics of electron produced by two-photon ionization of liquid
      polyols. II. Propanediols.
AB  - Temporal evolution of transient absorption spectra of electrons produced by two
      photon ionization of two isomers, propane-1,2-diol (12PD) and propane-1,3-diol
      (13PD), with 263 nm femtosecond laser pulses has been studied on picosecond time
      scale. The two-photon absorption coefficients of 12PD and 13PD at 263 nm were
      determined to be beta = (2.0 +/- 0.3) x 10(-11) and (2.4 +/- 0.3) x 10(-11) m W(
      1), respectively. Time-resolved absorption spectra ranging from 440 to 720 nm
      have been measured, showing a blue shift for the first tens of picoseconds for
      both solvents. However, the observed solvation dynamics of electron appears
      faster in 13PD than in 12PD. The transient signals of electron solvation have
      then been reconstructed with different models (stepwise mechanism or continuous
      relaxation model) using a Bayesian data analysis method. Results are discussed,
      compared with those previously obtained in ethylene glycol (J. Phys. Chem. A
      2006, 110, 1705) and corroborate the interpretation, according to which the
      solvation of electrons is mainly governed by continuous solvent molecular
      motions.

PMID- 17511429
TI  - Optical properties of the phosphorescent trinuclear copper(I) complexes of
      pyrazolates: insights from theory.
AB  - Theoretical investigations have been performed to explore the optical properties
      of {[3,5-(CF3)(2)Pz]Cu}3 in monomeric and dimeric forms using TD-DFT approaches.
      The emission of all complexes originates from the lowest triplet excited-states
      (T1), and the corresponding emissive states are assigned as the mixture of the
      metal-centered charge transfer and ligand-to-metal charge transfer. The features
      of the emission spectrum are clarified in detail. The bulk emission spectrum of
      complex is mainly determined by the stacked dimers rather than the individual
      monomers. The predicted maximum emission wavelength (lambda(em)) are in good
      agreement with experimental values, indicating that the phosphorescence bands can
      be assigned to two different conformations for the neighboring stacked dimers
      sharing the same monomer in the complex. Energy transfer from T1 of one stacked
      dimer to the neighboring one is responsible for the disappearance of the
      shoulder, leaving only the main peak upon heating. With the aim to reveal the
      conformational dependence for the triplet excited-state emission spectrum, the
      optical properties of various stacked dimers with different conformations are
      investigated by varying the relative arrangements through changing inter-monomer
      distance or rotational angles for the dimer which is responsible for the main
      peak emission. Calculation results suggest that the shortest intermolecular
      Cu...Cu distance plays an important role in the emission spectra of the vertical-
      and tilting-movement dimers, which is ascribed to the variation of the energy gap
      for the frontier molecular orbitals involved in the main emitting transition. The
      blue shift of lambda(em) in parallel-movement and rotational dimers can be traced
      back to the variation of the mutual spatial orientation. Therefore, the
      modulation of the extent of movement or rotational angles for stacked dimers by
      external perturbations creates new possibilities for the design of molecular
      light-emitting devices.

PMID- 17511430
TI  - Theoretical investigation of hyperthermal reactions at the gas-liquid interface:
      O (3P) and squalane.
AB  - Hyperthermal collisions (5 eV) of ground-state atomic oxygen [O ((3)P)] with a
      liquid-saturated hydrocarbon, squalane (C(30)H(62)), have been studied using
      QM/MM hybrid "on-the-fly" direct dynamics. The surface structure of the liquid
      squalane is obtained from a classical molecular dynamics simulation using the
      OPLS-AA force field. The MSINDO semiempirical Hamiltonian is combined with OPLS
      AA for the QM/MM calculations. In order to achieve a more consistent and
      efficient simulation of the collisions, we implemented a dynamic partitioning of
      the QM and MM atoms in which atoms are assigned to QM or MM regions based on
      their proximity to "seed" (open-shell) atoms that determine where bond
      making/breaking can occur. In addition, the number of seed atoms is allowed to
      increase or decrease as time evolves so that multiple reactive events can be
      described. The results show that H abstraction is the most important process for
      all incident angles, with H elimination, double H abstraction, and C-C bond
      cleavage also being important. A number of properties of these reactive channels,
      as well as inelastic nonreactive scattering, are investigated, including angular
      and translational energy distributions, the effect of incident collision angle,
      variation with depth of the reactive event within the liquid, with the reaction
      site on the hydrocarbon, and the effect of dynamics before and after reaction
      (direct reaction versus trapping reaction-desorption).

PMID- 17511431
TI  - Thermochemical and kinetic analysis on the reactions of O2 with products from OH
      addition to isobutene, 2-hydroxy-1,1-dimethylethyl, and 2-hydroxy-2-methylpropyl
      radicals: HO2 formation from oxidation of neopentane, Part II.
AB  - Unimolecular dissociation of a neopentyl radical to isobutene and methyl radical
      is competitive with the neopentyl association with O2 ((3)Sigma(g)-) in thermal
      oxidative systems. Furthermore, both isobutene and the OH radical are important
      primary products from the reactions of neopentyl with O2. Consequently, the
      reactions of O2 with the 2-hydroxy-1,1-dimethylethyl and 2-hydroxy-2-methylpropyl
      radicals resulting from the OH addition to isobutene are important to
      understanding the oxidation of neopentane and other branched hydrocarbons.
      Reactions that correspond to the association of radical adducts with
      O2((3)Sigma(g)-) involve chemically activated peroxy intermediates, which can
      isomerize and react to form one of several products before stabilization. The
      above reaction systems were analyzed with ab initio and density functional
      calculations to evaluate the thermochemistry, reaction paths, and kinetics that
      are important in neopentyl radical oxidation. The stationary points of potential
      energy surfaces were analyzed based on the enthalpies calculated at the CBS-Q
      level. The entropies, S(degrees)298, and heat capacities, C(p)(T), (0 <or= T/K
      <or= 1500), from vibration, translation, and external rotation contributions were
      calculated using statistical mechanics based on the vibrational frequencies and
      structures obtained from the density functional study. The hindered internal
      rotor contributions to S(degrees)298 and C(p)(T) were calculated by solving the
      Schrodinger equation with free rotor wave functions, and the partition
      coefficients were treated by direct integration over energy levels of the
      internal rotation potentials. Enthalpies of formation (DeltaH(f)(degrees)298)
      were determined using isodesmic reaction analysis. The DeltaH(f)(degrees)298
      values of (CH3)2C*CH(2)OH, (CH3)2C(OO*)CH(2)OH, (CH3)2C(OH)C*H2, and
      (CH3)2C(OH)CH(2)OO* radicals were determined to be -23.3, -62.2, -24.2, and -61.8
      kcal mol(-1), respectively. Elementary rate constants were calculated from
      canonical transition state theory, and pressure-dependent rate constants for
      multichannel reaction systems were calculated as functions of pressure and
      temperature using multifrequency quantum Rice-Ramsperger-Kassel (QRRK) analysis
      for k(E) and a master equation for pressure falloff. Kinetic parameters for
      intermediate and product formation channels of the above reaction systems are
      presented as functions of temperature and pressure.

PMID- 17511432
TI  - Systematic effect of benzo-annelation on oxo-hydroxy tautomerism of heterocyclic
      compounds. Experimental matrix-isolation and theoretical study.
AB  - Oxo-hydroxy tautomerism and phototautomerism of 2-quinolinone, 1-isoquinolinone,
      3-hydroxyisoquinoline, 2-quinoxalinone, and 4-quinazolinone were studied using
      the matrix-isolation technique. These compounds contain a benzene ring fused with
      a heterocyclic ring of 2-pyridinone, 2-pyrazinone, or 4-pyrimidinone. It turned
      out that direct attachment of a benzene ring to a heterocycle leads to a very
      pronounced increase of the relative stability of oxo tautomers (in comparison
      with the tautomerism of the parent compounds 2-pyridinone, 2-pyrazinone, and 4
      pyrimidinone). The only exception concerns 3-hydroxyisoquinoline, where fusion
      with a benzene ring enforces rearrangement of the double- and single-bond system
      in the oxo tautomer. This destabilizes substantially the oxo form with respect to
      the hydroxy tautomer. The ratios of population of the oxo and hydroxy tautomers
      observed in Ar matrixes correspond to the tautomeric equilibria of the compounds
      in the gas phase. These equilibria were well reproduced by theoretical
      calculations carried out at the QCISD and QCISD(T) levels. The combined
      experimental and theoretical results reveal links between aromaticity and
      tautomerism. Moreover, a UV-induced phototautomeric reaction transforming the oxo
      forms into the hydroxy tautomers was observed for all (except 3
      hydroxyisoquinoline) studied compounds. This photoeffect allowed separation of
      the IR spectra of the tautomers in question.

PMID- 17511433
TI  - HeI photoelectron spectroscopy and theoretical study of trichloromethanesulfenyl
      acetate, CCl3SOC(O)CH3, and trichloromethanesulfenyl trifluoroacetate,
      CCl3SOC(O)CF3.
AB  - Two novel species, trichloromethanesulfenyl acetate, CCl(3)SOC(O)CH(3), and
      trichloromethanesulfenyl trifluoroacetate, CCl(3)SOC(O)CF(3), have been generated
      in situ by the heterogeneous reactions between trichloromethanesulfenyl chloride,
      CCl(3)SCl, and corresponding silver salts, silver acetate (AgOC(O)CH(3)) and
      silver trifluoroacetate (AgOC(O)CF(3)), respectively. Photoelectron spectroscopy
      and quantum chemical calculations are performed to investigate these two
      molecules, together with their precursor, CCl(3)SCl. Both of these two compounds
      may exist in the gas phase as a mixture of gauche and trans conformations. As for
      the dihedral angles delta(RSOR') of the gauche conformers, 107.0 degrees and
      108.5 degrees are derived by theoretical calculations (at the B3LYP/6-311+G(3df)
      level) for CCl(3)SOC(O)CH(3) and CCl(3)SOC(O)CF(3), respectively. The first
      vertical ionization energies of CCl(3)SOC(O)CH(3) and CCl(3)SOC(O)CF(3), which
      have been determined by photoelectron spectroscopy, are 9.67 and 10.34 eV,
      respectively. According to the experimental results and theoretical analysis, the
      first ionization energy of these two molecules both come from the ionization of
      the lone pair electron of S atom.

PMID- 17511434
TI  - Basis set limit CCSD(T) harmonic vibrational frequencies.
AB  - Benchmark, frozen-core CCSD(T) equilibrium harmonic vibrational frequencies of 12
      closed-shell and five open-shell molecules are computed to within 1 cm-1 of the
      basis set limit using the explicitly correlated CCSD(T)-R12 method. The
      convergence of the standard CCSD(T) method with the one-particle basis sets of
      Dunning and co-workers is examined and found to be slow, with mean and maximum
      absolute errors of 1.3 and 3.5 cm-1 remaining at the cc-pV6Z level. Finite basis
      set effects do not appear to introduce systematic errors in equilibrium harmonic
      frequencies, and mean absolute errors reduce by a factor of 2 for each basis set
      cardinal number increment. The convergence of individual equilibrium harmonic
      frequencies is not guaranteed to be monotonic due to the associated shift in the
      equilibrium structure. The inclusion of computed scalar relativistic effects and
      previously available corrections for core-valence correlation and higher-order
      excitations in the cluster operator results in an agreement with experimentally
      derived harmonic frequencies of 0.1, 0.3, and -0.4 cm-1 for HF, N2, and CO,
      respectively. F2 continues to present a challenge to computational chemistry with
      an error of 3.2 cm-1, primarily resulting from the high basis set dependence of
      the quadruples contribution.

PMID- 17511435
TI  - Model systems for probing metal cation hydration: the V+(H2O) and ArV+(H2O)
      complexes.
AB  - In support of mass-selected infrared photodissociation (IRPD) spectroscopy
      experiments, coupled-cluster methods including all single and double excitations
      (CCSD) and a perturbative contribution from connected triple excitations
      [CCSD(T)] have been used to study the V+(H2O) and ArV+(H2O) complexes.
      Equilibrium geometries, harmonic vibrational frequencies, and dissociation
      energies were computed for the four lowest-lying quintet states (5A1, 5A2, 5B1,
      and 5B2), all of which appear within a 6 kcal mol(-1) energy range. Moreover,
      anharmonic vibrational analyses with complete quartic force fields were executed
      for the 5A1 states of V+(H2O) and ArV+(H2O). Two different basis sets were used:
      a Wachters+f V[8s6p4d1f] basis with triple-zeta plus polarization (TZP) for O, H,
      and Ar; and an Ahlrichs QZVPP V[11s6p5d3f2g] and Ar[9s6p4d2f1g] basis with aug-cc
      pVQZ for O and H. The ground state is predicted to be 5A1 for V+(H2O), but argon
      tagging changes the lowest-lying state to 5B1 for ArV+(H2O). Our computations
      show an opening of 2 degrees -3 degrees in the equilibrium bond angle of H2O due
      to its interaction with the metal ion. Zero-point vibrational averaging increases
      the effective bond angle further by 2.0 degrees -2.5 degrees, mostly because of
      off-axis motion of the heavy vanadium atom rather than changes in the water
      bending potential. The total theoretical shift in the bond angle of about +4
      degrees is significantly less than the widening near 9 degrees deduced from IRPD
      experiments. The binding energies (D0) for the successive addition of H2O and Ar
      to the vanadium cation are 36.2 and 9.4 kcal mol(-1), respectively.

PMID- 17511436
TI  - Potential energy surface for asymmetrically substituted reactions of type CWXYZ +
      A. Kinetics study.
AB  - The CHClF(2) + Cl --> ClH + CClF(2) gas-phase abstraction reaction was chosen as
      a model of asymmetrically substituted polyatomic reactions of type CWXYZ + A -->
      products. The analytical potential energy surface for this reaction was
      constructed with suitable functional forms to represent vibrational modes, and
      calibrated with respect to experimental thermal rate constants which are
      available over the temperature range 296-410 K. On this surface, the thermal rate
      constants were calculated using variational transition-state theory with
      semiclassical transmission coefficients over a wider temperature range, 200-2500
      K, therefore obtaining kinetics information at lower and higher temperatures than
      are experimentally available. This surface was also used to analyze dynamical
      features, such as tunneling and reaction-path curvature. In the former, the
      influence of the tunneling factor was important since a light hydrogen atom
      passes through the barrier. In the latter, it was found that vibrational
      excitation of the C-F and C-Cl stretching modes can be expected in the exit
      channel.

PMID- 17511437
TI  - Extending the power of quantum chemistry to large systems with the fragment
      molecular orbital method.
AB  - Following the brief review of the modern fragment-based methods and other
      approaches to perform quantum-mechanical calculations of large systems, the
      theoretical development of the fragment molecular orbital method (FMO) is covered
      in detail, with the emphasis on the physical properties, which can be computed
      with FMO. The FMO-based polarizable continuum model (PCM) for treating the
      solvent effects in large systems and the pair interaction energy decomposition
      analysis (PIEDA) are described in some detail, and a range of applications of FMO
      to biological studies is introduced. The factors determining the relative
      stability of polypeptide conformers (alpha-helix, beta-turn, and extended form)
      are elucidated using FMO/PCM and PIEDA, and the interactions in the Trp-cage
      miniprotein construct (PDB: 1L2Y) are analyzed using PIEDA.

PMID- 17511438
TI  - First principles NMR calculations by fragmentation.
AB  - The nuclear magnetic shielding tensor is a molecular property that can be
      computed from first principles. In this work we show that by utilizing the
      fragmentation approach, one is able to accurately compute this property for a
      large class of molecules. This is of great significance because the computational
      expense required in the evaluation of the shielding tensor for all nuclei in a
      large molecule is now subject to near linear scaling. On the basis of previous
      studies and this work, it is also very likely that all molecular properties that
      can be expressed as derivatives of the total energy of the system are also
      amenable to accurate evaluation via fragmentation. If only the chemical shifts
      for nuclei in a small part of a large molecule are of interest, then only those
      molecular fragments containing those nuclei need to have their shielding tensors
      evaluated. Further, the fragmentation approach allows one to construct a database
      of molecular fragments that could, in principle, be used in the NMR
      characterization of molecules and at the same time provide possible three
      dimensional representations of these molecules.

PMID- 17511439
TI  - Synthesis and biological evaluation of (+/-)-abyssinone II and its analogues as
      aromatase inhibitors for chemoprevention of breast cancer.
AB  - An efficient and economical synthesis of the naturally occurring aromatase
      inhibitor abyssinone II was performed. The synthesis features an optimized
      aromatic prenylation reaction in which an arylcopper intermediate is reacted with
      prenyl bromide to afford a key intermediate that was converted to a prenylated
      aromatic aldehyde. Condensation of the aldehyde with an o-hydroxyacetophenone
      under Claisen-Schmidt conditions afforded a chalcone that was deprotected and
      cyclized in the presence of sodium acetate in refluxing ethanol to afford (+/-)
      abyssinone II. The synthesis proved to be versatile enough to provide an array of
      abyssinone II derivatives that were evaluated as aromatase inhibitors.
      Methylation of the 4'-hydroxyl group of (+/-)-abyssinone II resulted in a
      significant increase in aromatase inhibitory activity, and further smaller
      increases in activity resulted from the methylation of the 7-hydroxyl group and
      removal of the prenyl side chain. As a result of these structural changes, the
      most active flavanone of the series was 20 times more potent than (+/-)
      abyssinone II (IC50 40.95 microM).

PMID- 17511440
TI  - Linear TMC-95-based proteasome inhibitors.
AB  - We have designed and evaluated 45 linear analogues of the natural constrained
      cyclopeptide TMC-95A. These synthetically less demanding molecules are based on
      the tripeptide sequence Y-N-W of TMC-95A. Structural variations in the amino acid
      side chains and termini greatly influenced both the efficiency and selectivity of
      action on a given type of active site. Inhibition constants were submicromolar
      (Ki approximately 300 nM) despite the absence of the entropically favorable
      constrained conformation that is characteristic of TMC-95A and its cyclic
      analogues. These linear compounds were readily prepared and reasonably stable in
      culture medium and could be optimized to inhibit one, two, or all three
      proteasome catalytic sites. Cytotoxicity assays performed on a series of human
      tumor cell lines identified the most potent inhibitors in cells.

PMID- 17511441
TI  - Recent advances in chemoinformatics.
AB  - Chemoinformatics is a large scientific discipline that deals with the storage,
      organization, management, retrieval, analysis, dissemination, visualization, and
      use of chemical information. Chemoinformatics techniques are used extensively in
      drug discovery and development. Although many consider it a mature field, the
      advent of high-throughput experimental techniques and the need to analyze very
      large data sets have brought new life and challenges to it. Here, we review a
      selection of papers published in 2006 that caught our attention with regard to
      the novelty of the methodology that was presented. The field is seeing
      significant growth, which will be further catalyzed by the widespread
      availability of public databases to support the development and validation of new
      approaches.

PMID- 17511442
TI  - Mechanism of the Kolbe-Schmitt reaction. Structure of the intermediate potassium
      phenoxide-CO(2) complex.
AB  - Our investigation elucidates the structure of the intermediate in the first stage
      of the carboxylation reaction of potassium phenoxide. Under the reduced pressure
      of carbon dioxide the complex is not solvated with the CO(2) molecules. Under the
      conditions of the carboxylation reaction the potassium phenoxide-carbon dioxide
      complex is solvated with one or two CO(2) molecules. One of the added CO(2)
      moieties performs an electrophilic attack on the benzene ring, whereas the old
      CO(2) moiety becomes a molecule of solvent. Our findings are in good accord with
      the experimental results obtained by the NMR and IR measurements.

PMID- 17511443
TI  - Synthesis, structure, and luminescent and magnetic properties of novel lanthanide
      metal-organic frameworks with zeolite-like topology.
AB  - A series of microporous lanthanide metal-organic frameworks [Ln(BTC)(DMF)(2) x
      H(2)O, Ln = Tb (1), Dy (2), Ho (3), Er (4), Tm (5), Yb (6); DMF = N,N'
      dimethylformamide] with 4 x 4 x 4 x 6 x 6 x 8 topology, which is very common in
      the zeolite topologies, have been synthesized under mild conditions. The single
      crystal X-ray diffraction analysis reveals that they exhibit the same three
      dimensional (3D) architecture and crystallize in monoclinic symmetry space group
      C2/c. Organic and inorganic four-connected nodes link each other to form a 3D
      open framework. The framework contains approximate 13 Angstrom x 7 Angstrom
      rectangle channels along the [1,1,0] and [1,-1,0] directions, respectively. The
      luminescent properties of these complexes have been studied, and complex 1 shows
      a Tb(3+) characteristic emission in the range of 450-650 nm at room temperature.
      Complexes 1-5 exhibit antiferromagnetic interaction between Ln(3+) ions. The
      water sorption isotherm shows that about 15 water molecules per unit cell can be
      adsorbed into the micropores of dehydrated complex 4.

PMID- 17511444
TI  - Reversible, electrochemically controlled binding of phosphine to iron and cobalt
      bis(dithiolene) complexes.
AB  - The homoleptic bis(dithiolene) complexes [M(S(2)C(2)R(2))(2)](2) (M = Fe, Co; R =
      p-anisyl) undergo two successive reductions to form anions that display
      [M(S(2)C(2)R(2))(2)](2)(2-) <--> 2[M(S(2)C(2)R(2))(2)](1-) solution equilibria.
      The neutral dimers react with Ph3P to form square pyramidal
      [M(Ph(3)P)(S(2)C(2)R(2))(2)](0). Voltammetric measurements upon
      [M(Ph(3)P)(S(2)C(2)R(2))(2)](0) in CH(2)Cl(2) reveal only irreversible features
      at negative potentials, consistent with Ph(3)P dissociation upon reduction.
      Dissociation and reassociation of Ph(3)P from and to
      [Fe(Ph(3)P)(S(2)C(2)R(2))(2)](0) is demonstrated by spectroelectrochemical
      measurements. These collective observations form the basis for a cycle of
      reversible, electrochemically controlled binding of Ph(3)P to
      [M(S(2)C(2)R(2))(2)](2) (M = Fe, Co; R = p-anisyl). All members of the cycle
      ([M(S(2)C(2)R(2))(2)](2)(0), [M(S(2)C(2)R(2))(2)](2)(1-),
      [MM(S(2)C(2)R(2))(2)](2)(2-), [M(S(2)C(2)R(2))(2)](1-),
      [M(Ph(3)P)(S(2)C(2)R(2))(2)]) for M = Fe, Co have been characterized by
      crystallography. Square planar [Fe(S(2)C(2)R(2))(2)](1-) is the first such iron
      dithiolene species to be structurally identified and reveals Fe-S bond distances
      of 2.172(1) and 2.179(1) Angstrom, which are appreciably shorter than those in
      corresponding square planar dianions.

PMID- 17511445
TI  - Oxidation of tertiary silanes by osmium tetroxide.
AB  - In the presence of an excess of pyridine ligand L, osmium tetroxide oxidizes
      tertiary silanes (Et(3)SiH, (i)Pr(3)SiH, Ph(3)SiH, or PhMe(2)SiH) to the
      corresponding silanols. With L = 4-tert-butylpyridine ((t)Bupy), OsO(4)((t)Bupy)
      oxidizes Et(3)SiH and PhMe(2)SiH to yield 100 +/- 2% of silanol and the
      structurally characterized osmium(VI) mu-oxo dimer [OsO(2)((t)Bupy)(2)](2)(mu
      O)(2) (1a). With L = pyridine (py), only 40-60% yields of R(3)SiOH are obtained,
      apparently because of coprecipitation of osmium(VIII) with [Os(O)(2)py(2)](2)(mu
      O)(2) (1b). Excess silane in these reactions causes further reduction of the OsVI
      products, and similar osmium "over-reduction" is observed with PhSiH(3),
      Bu(3)SnH, and boranes. The pathway for OsO(4)(L) + R(3)SiH involves an
      intermediate, which forms rapidly at 200 K and decays more slowly to products.
      NMR and IR spectra indicate that the intermediate is a monomeric Os(VI)-hydroxo
      siloxo complex, trans-cis-cis-Os(O)(2)L(2)(OH)(OSiR(3)). Mechanistic studies and
      density functional theory calculations indicate that the intermediate is formed
      by the [3 + 2] addition of an Si-H bond across an O=Os=O fragment. This is the
      first direct observation of a [3 + 2] intermediate in a sigma-bond oxidation,
      though such species have previously been implicated in reactions of H-H and C-H
      bonds with OsO(4)(L) and RuO(4).

PMID- 17511446
TI  - Synthesis, structure, redox properties, and catalytic activity of new ruthenium
      complexes containing neutral or anionic and facial or meridional ligands: an
      evaluation of electronic and geometrical effects.
AB  - The synthesis of a family of new Ru complexes containing meridional or facial
      tridentate ligands with the general formula [Ru(II)(T)(D)(X)](n+) [T = 2,2':6',2'
      '-terpyridine or tripyrazolylmethane; D = 4,4'-dibenzyl-4,4',5,5'-tetrahydro-2,2'
      bioxazole (S,S-box-C) or 2-[((1'S)-1'-(hydroxymethyl)-2'-phenyl)ethylcarboxamide]
      (4S)-4-benzyl-4,5-dihydrooxazole (S,S-box-O); X = Cl, H(2)O, MeCN or pyridine]
      has been described. All complexes have been spectroscopically characterized in
      solution through (1)H NMR and UV-vis techniques. Furthermore, all of the chloro
      complexes presented here have also been characterized in the solid state through
      monocrystal X-ray diffraction analysis. The oxazolinic S,S-box-C ligands undergo
      a Ru-assisted hydrolysis reaction generating the corresponding amidate anionic
      oxazolinic ligands S,S-box-O, which are also strongly attached to the metal
      center and produce a strong sigma-donation effect over the Ru metal center. The
      redox properties of all complexes have also been studied by means of cyclic
      voltammetry, strongly reflecting the nature of the ligands; both effects,
      geometrical (facial vs meridional) and electronic (neutral vs anionic), can be
      unveiled and rationalized. Finally, the reactivity of the Ru-OH(2) complexes has
      been tested with regard to the epoxidation of trans-stilbene, and it has been
      shown that, in this particular case, the reactivity is practically not dependent
      on the redox potentials of the catalyst but, in sharp contrast, it is strongly
      dependent on the geometry of the tridentate ligands.

PMID- 17511447
TI  - Ferromagnetic vs antiferromagnetic coupling in bis(mu-phenoxo)dicopper(II)
      complexes. Tuning of the nature of exchange coupling by remote ligand
      substituents.
AB  - Two bis(mu-phenoxo)dicopper(II) complexes, [(L(CH3))(2)Cu(2)] (1) and [(L(t
      Bu))(2)Cu(2)] (2), where L(CH3) and L(t-Bu) represent the dianions of
      (methylamino)-N,N-bis(2-methylene-4,6-dimethylphenol) and of (methylamino)-N,N
      bis(2-methylene-4,6-di-tert-butylphenol), respectively, are reported to
      demonstrate the effect of remote substituents on the nature of exchange coupling
      interactions between the copper(II) centers. In contrast to 1, which is as usual
      antiferromagnetically coupled, complex 2 is a rare example of a ferromagnetically
      coupled diphenoxodicopper(II) complex.

PMID- 17511448
TI  - Characterization and electrochemical properties of molecular icosanuclear and
      bidimensional hexanuclear Cu(II) azido polyoxometalates.
AB  - Two new Cu(II) azido polyoxometalates compounds have been synthesized, and their
      structures were determined by X-ray crystallography. The compound
      Na(14)[SiW(9)O(34)Cu(3)(N(3))(2)(OH)(H(2)O)](2) x 24H(2)O (1) is built from two
      [SiW(9)O(34)Cu(3)(mu(1,1,3)-N(3))(2)(mu-OH)(H(2)O)](7-) subunits where the copper
      centers, connected by two azido ligands and one hydroxo group, form a nearly
      equilateral triangle. The two subunits are related by an inversion center and
      connected via the two mu(1,1,3)-N(3) ligands in an end-to-end fashion, affording
      a hexanuclear Cu(II) cluster. Linkage of these fragments via Cu-O=W bonds leads
      to a bidimensional arrangement of the polyoxometalate units. The complex
      LiK(14)Na(9)[P(8)W(48)O(184)Cu(20)(N(3))(6)(OH)(18)] x 60H(2)O (2) consists of
      two {Cu(5)(OH)(4)}(6+) and two {Cu(5)(OH)(2)(mu(1,1,3,3)-N(3))}(7+) subunits
      connected via four mu-OH and four mu(1,1)-N(3) additional ligands, the 20 copper
      centers being encapsulated in the [P(8)W(48)O(184)](40-) crown polyoxotungstate
      ligand. 1 represents the first multidimensional compound based on azido
      polyoxometalate (POM) units, and 2 represents by far the largest azido POM
      complex isolated to date. Magnetic measurements revealed an overall
      antiferromagnetic behavior for both compounds. Nevertheless, the study of the
      variation of the magnetization with the applied field indicates that 1 possesses
      a triplet ground state, which can be attributed to weak ferromagnetic interaction
      between the S = 1/2 triangular subunits. The stability of 1 and 2 evidenced by UV
      vis spectroscopy and gel filtration chromatography, in particular at pH 5, has
      allowed a detailed study of their redox and electrocatalytic properties. For both
      compounds, the stability of the Cu(II)/Cu(I) couple is remarkable compared with
      the observations made in other Cu(II)-substituted POMs. Electrochemical quartz
      crystal microbalance measurements clearly demonstrate that the formation of the
      Cu(I) species occurs neatly without the formation of Cu(0). The accumulation of
      such Cu(II) centers within the complexes is a favorable condition to envision
      applications involving several electrons. The electrocatalytic reduction of
      dioxygen and hydrogen peroxide was achieved efficiently and has shown that the
      reactivity increases with the nuclearity and/or the Cu/W ratio of the POM
      complex. The dioxygen reduction is an overall four-electron process with water as
      the final product. Finally, the reduction of the W centers triggers a strong
      electrocatalysis of solvent reduction.

PMID- 17511449
TI  - Wirelike dinuclear ruthenium complexes connected by bis(ethynyl)oligothiophene.
AB  - Preparation and characterization of a series of rodlike binuclear ruthenium
      polyynediyl complexes capped with redox-active organometallic fragments
      [(bph)(PPh3)2Ru]+ (bph=N-(benzoyl)-N'-(picolinylidene)-hydrazine) or
      [(Phtpy)(PPh3)2Ru]2+ (Phtpy=4'-phenyl-2,2':6',2' '-terpyridine) have been carried
      out. The length of the molecular rods is extended by successive insertion of 2,5
      thiophene or 1,4-phenylene spacers in the bridging ligands. Oxidation of
      thiophene-containing Ru2II,II complexes induces isolation of stable Ru2II,III or
      Ru2III,III species. Electrochemical and UV-vis-NIR spectral studies demonstrate
      that the polyynediyl bridges with 2,5-thiophene units are more favorable for
      metal-metal charge transfer compared with those containing the same number of 1,4
      phenylene units. Successive increase of thiophene spacers in mixed-valence
      complexes {RuII}-CC(C4H2S)mCC-{RuIII} (m=1, 2, 3) induced a smooth transition
      from almost electronic delocalization (m=1) to localization (m=3). For binuclear
      ruthenium complexes with intramolecular electron transfer transmitted across nine
      Ru-C and C-C bonds, electronic conveying capability follows {Ru}-CC(CC)2CC
      {Ru}>{Ru}-CC(C4H2S)CC-{Ru}>{Ru}-CC(C6H4)CC-{Ru}>{Ru}-CC(CH=CH)2CC-{Ru}. It is
      revealed that molecular wires capped with electron-rich (bph)(PPh3)2Ru endgroups
      are much more favorable for electronic communication than the corresponding
      electron-deficient (Phtpy)(PPh3)2Ru-containing counterparts. The intermetallic
      electronic communication is fine-tuned by modification of both the bridging
      spacers and the ancillary ligands.

PMID- 17511450
TI  - After 20 years, theoretical evidence that "AuF(7)" is actually AuF(5) x F(2).
AB  - Quantum-chemical calculations at the DFT (BP86, PBE, TPSS, B3LYP, PBE0), MP2,
      CCSD, and CCSD(T) levels have been carried out to characterize the putative
      AuF(7) reported in 1986 by Timakov et al. Our calculations indicate clearly that
      the species claimed to be AuF(7) had not been synthesized. Instead, a new gold
      fluoride complex AuF(7) x F2 was prepared. This complex is 205 kJ mol(-1) more
      stable than the proposed AuF(7) species, and the elimination of F(2) is
      calculated to be endothermic. This is consistent with the reported stability of
      the product. A reported experimental vibrational frequency at 734 cm(-1) was
      verified computationally to be the F-F stretching mode of the end-on coordinated
      F2 molecule. This result is in line with the recently published trends in the
      highest attainable oxidation states of the 5d transition metals where Au(V)
      remains the highest oxidation state of gold.

PMID- 17511451
TI  - Redox behavior of cyclo[6]pyrrole in the formation of a uranyl complex.
AB  - A uranyl complex, the first metal complex to be formed from the cyclo[n]pyrrole
      series of expanded porphyrins, is formed when cyclo[6]pyrrole is treated with the
      uranyl cation under aerobic conditions. Spectroscopic, spectroelectrochemical,
      and electron spin resonance data of this species are consistent with the ligand
      in the complex being oxidized to an antiaromatic form.

PMID- 17511452
TI  - Preparation of tungsten alkyl alkylidene alkylidyne complexes and kinetic studies
      of their formation.
AB  - An equilibrium mixture of alkyl alkylidyne W(CH2SiMe3)3(CSiMe3)(PMe3) (1a) and
      its bis(alkylidene) tautomer W(CH2SiMe3)2(=CHSiMe3)2(PMe3) (1b) has been found to
      undergo an alpha-hydrogen abstraction reaction in the presence of PMe3 to form
      alkyl alkylidene alkylidyne W(CH2SiMe3)(=CHSiMe3)(CSiMe3)(PMe3)2 (2). In the
      presence of PMe3, the formation of 2 follows first-order kinetics, and the
      observed rate constant was found to be independent of the concentration of PMe3.
      The activation parameters for the formation of 2 are Delta H = 28.3(1.7) kcal/mol
      and Delta S = 3(5) eu. In the presence of PMe2Ph, an equilibrium mixture of
      W(CH2SiMe3)3(CSiMe3)(PMe2Ph) (3a) and its bis(alkylidene) tautomer
      W(CH2SiMe3)2(=CHSiMe3)2(PMe2Ph) (3b) was similarly converted to
      W(CH2SiMe3)(=CHSiMe3)(CSiMe3)(PMe2Ph)2 (4). The observed rate of this reaction
      was also independent of the concentration of PMe2Ph. These observations suggest a
      pathway in which the tautomeric mixtures 1a,b and 3a,b undergo rate-determining,
      alpha-hydrogen abstraction, followed by phosphine coordination, resulting in the
      formation of the alkyl alkylidene alkylidyne complexes 2 and 4.

PMID- 17511453
TI  - Nanosize effect on high-rate Li-ion intercalation in LiCoO2 electrode.
AB  - Recently, battery technology has come to require a higher rate capability. The
      main difficulty in high-rate charge-discharge experiments is kinetic problems due
      to the slow diffusion of Li-ions in electrodes. Nanosizing is a popular way to
      achieve a higher surface area and shorter Li-ion diffusion length for fast
      diffusion. However, while various nanoelectrodes that provide excellent high-rate
      capability have been synthesized, a size-controlled synthesis and a systematic
      study of nanocrystalline LiCoO2 have not been carried out because of the
      difficulty in controlling the size. We have established the size-controlled
      synthesis of nanocrystalline LiCoO2 through a hydrothermal reaction and, for the
      first time, clarified the structural and electrochemical properties of this
      intercalation cathode material. Lattice expansion in nanocrystalline LiCoO2 was
      found from powder X-ray diffraction measurements and Raman spectroscopy.
      Electrochemical measurements and theoretical analyses on nanocrystalline LiCoO2
      revealed that extreme size reduction below 15 nm was not favorable for most
      applications. An excellent high-rate capability (65% of the 1 C rate capability
      at 100 C) was observed in nanocrystalline LiCoO2 with an appropriate particle
      size of 17 nm.

PMID- 17511454
TI  - Colloid chemical reaction route to the preparation of nearly monodispersed
      perylene nanoparticles: size-tunable synthesis and three-dimensional self
      organization.
AB  - By employing a colloid chemical reaction method we demonstrate the preparation of
      organic nanoparticles composed of perylene molecules (PeNPs) based on the
      reduction of perylene perchlorate by Br- anions in the presence of cetyl
      trimethyl ammonium bromide (CTA+Br-) in acetonitrile. A discrete nucleation
      event, followed by a slower controlled growth on the existing particles, is
      identified during formation of PeNPs. By changing the growth parameters, such as
      the monomer concentration and the method of injection, quasi-spherical PeNPs with
      controllable sizes from 25 to 90 nm could be obtained. The homogeneous solution
      phase of this method makes it capable of large-scale synthesis of PeNPs with a
      size distribution (<10%) that is improved by formation of a protective layer of
      CTA+ around the PeNPs. The three-dimensional, hierarchical self-organization of
      25-nm PeNPs building blocks is observed to form nanobelts and square nanorods,
      possibly templated by the CTA+ lamellar micelle structures in acetonitrile.
      Spectroscopic results reveal two kinds of trends in the development of the
      optical properties of perylene as they evolve from the molecular to the bulk
      phase in the nanometer range. The so-called size dependence is evidenced by a
      switch from Y-type to E-type excimers as the size of the PeNPs increased from 25
      to 90 nm. As the 25-nm PeNPs organize into nanobelts or square nanorods the
      oscillator strength of the Y-type excimers is relatively enhanced. That is,
      collective phenomena develop as the proximal particles interact in the glassy
      solids. Our very recent results indicate that this colloid chemical reaction
      method can also be applied to other organic compounds.

PMID- 17511455
TI  - Synthesis, characterization, and metal coordinating ability of multifunctional
      carbohydrate-containing compounds for Alzheimer's therapy.
AB  - Dysfunctional interactions of metal ions, especially Cu, Zn, and Fe, with the
      amyloid-beta (A beta) peptide are hypothesized to play an important role in the
      etiology of Alzheimer's disease (AD). In addition to direct effects on A beta
      aggregation, both Cu and Fe catalyze the generation of reactive oxygen species
      (ROS) in the brain further contributing to neurodegeneration. Disruption of these
      aberrant metal-peptide interactions via chelation therapy holds considerable
      promise as a therapeutic strategy to combat this presently incurable disease. To
      this end, we developed two multifunctional carbohydrate-containing compounds N,N'
      bis[(5-beta-D-glucopyranosyloxy-2-hydroxy)benzyl]-N,N'-dimethyl-ethane-1,2
      diamine (H2GL1) and N,N'-bis[(5-beta-D-glucopyranosyloxy-3-tert-butyl-2
      hydroxy)benzyl]-N,N'-dimethyl-ethane-1,2-diamine (H2GL2) for brain-directed metal
      chelation and redistribution. Acidity constants were determined by potentiometry
      aided by UV-vis and 1H NMR measurements to identify the protonation sites of
      H2GL1,2. Intramolecular H bonding between the amine nitrogen atoms and the H
      atoms of the hydroxyl groups was determined to have an important stabilizing
      effect in solution for the H2GL1 and H2GL2 species. Both H2GL1 and H2GL2 were
      found to have significant antioxidant capacity on the basis of an in vitro
      antioxidant assay. The neutral metal complexes CuGL1, NiGL1, CuGL2, and NiGL2
      were synthesized and fully characterized. A square-planar arrangement of the
      tetradentate ligand around CuGL2 and NiGL2 was determined by X-ray
      crystallography with the sugar moieties remaining pendant. The coordination
      properties of H2GL1,2 were also investigated by potentiometry, and as expected,
      both ligands displayed a higher affinity for Cu2+ over Zn2+ with H2GL1 displaying
      better coordinating ability at physiological pH. Both H2GL1 and H2GL2 were found
      to reduce Zn2+- and Cu2+- induced Abeta1-40 aggregation in vitro, further
      demonstrating the potential of these multifunctional agents as AD therapeutics.

PMID- 17511456
TI  - Stereochemical control mechanisms in propylene polymerization mediated by C1
      symmetric CGC titanium catalyst centers.
AB  - This work analyzes stereochemical aspects of olefin polymerization processes
      mediated by the C1-symmetric constrained geometry catalyst H2Si(ind)(tBuN)TiCH3+
      (ind = indenyl), including the role of the cocatalyst/counteranion. The
      energetics of catalyst activation are first analyzed and shown to compare
      favorably with experiment. The energetics of heterolytic ion pair separation are
      next scrutinized, and the effects of solvation environment are assessed. Computed
      thermodynamic profiles for ethylene insertion at H2Si(ind)(tBuN)TiCH3+ indicate
      that the kinetics of insertion processes at the H2Si(ind)(tBuN)TiR+ cation can be
      analyzed in terms of SCF potential energies. We next compare the energetic
      profile for ethylene insertion at the naked H2Si(ind)(tBuN)TiCH3+ cation with
      that at the related H2Si(ind)(tBuN)TiCH3+H3CB(C6F5)3- ion pair to understand
      counterion effects. It is seen that the counterion, although affecting overall
      catalytic activity, does not significantly influence enchainment stereochemistry
      or polymer microtacticity. Next, the second ethylene insertion at
      H2Si(ind)(tBuN)Ti(nC3H7)+H3CB(C6F5)3- is analyzed to evaluate counteranion
      influence on the propagation barrier. It is found that the ethylene uptake
      transition state is energetically comparable to the first insertion transition
      state and that solvation has negligible effects on the energetic profile. These
      findings justify analysis of the propylene insertion process within the less
      computationally demanding "naked cation" model. Thus, monomer enchainment at
      H2Si(ind)(tBuN)TiR+ is analyzed for H2Si(ind)(tBuN)TiCH3+ + propylene (first
      insertion) and for H2Si(ind)(tBuN)Ti(iC4H6)+ + propylene (second insertion). Data
      describing the first insertion highlight the sterically dominated regioselection
      properties of the system with activation energies indicating that olefin
      insertion regiochemistry is predominantly 1,2 (primary), while the second
      insertion similarly reflects the catalyst stereoinduction properties, with steric
      effects introduced by the growing chain (mimicked by an isobutyl group)
      preferentially favoring insertion pathways that afford isotactic enrichment, in
      agreement with experiment.

PMID- 17511457
TI  - Iron diazoalkane chemistry: N-N bond hydrogenation and intramolecular C-H
      activation.

PMID- 17511458
TI  - Trityl radicals as persistent dual function pH and oxygen probes for in vivo
      electron paramagnetic resonance spectroscopy and imaging: concept and experiment.

PMID- 17511459
TI  - Enantioselective reductive coupling of acetylene to N-arylsulfonyl imines via
      rhodium catalyzed C-C bond-forming hydrogenation: (Z)-dienyl allylic amines.

PMID- 17511460
TI  - New approach for size- and shape-controlled preparation of Pd nanoparticles with
      organic ligands. Synthesis and application in catalysis.

PMID- 17511461
TI  - Amine-catalyzed direct aldol addition.

PMID- 17511462
TI  - Ring-closing reaction of allenic/propargylic anions generated by base treatment
      of sulfonylallenes.
AB  - The intramolecular trapping of allenyl/propargyl anions generated by base
      treatment of sulfonylallenes was investigated. Treatment of 1-(omega-iodoalkyl)-1
      (phenylsulfonyl)allenes with TBAF or NaH in DMF efficiently produced three- to
      seven-membered 1-ethynyl-1-(phenylsulfonyl) substituted carbocycles. The
      allenyl/propargyl anions could also be intramolecularly trapped using a terminal
      aldehyde or alpha,beta-unsaturated ester. The phenylsulfonyl group was found to
      be replaced by other electron-withdrawing functionalities like ketone and ester
      groups but not by an alkyl group for this novel ring-closing reaction.

PMID- 17511463
TI  - Development of sensitive crop-specific polymerase chain reaction assays using 5S
      DNA: applications in food traceability.
AB  - The 5S intergenic spacers were amplified using a common pair of primers and
      sequenced from four species (Brassica napus, Zea mays, Helianthus annuus, and
      Glycine max). Crop-specific assays were developed from primers designed from the
      spacers and tested to amplify corresponding DNAs in both conventional end-point
      and real-time polymerase chain reactions (PCRs). The high copy numbers of the 5S
      DNA in plants make it possible to detect very small amounts of DNA using this
      marker. This sensitivity made it possible to compare different DNA extraction
      methods for highly processed food products using 5S spacers, even allowing
      dilution of templates to overcome PCR inhibition.

PMID- 17511464
TI  - Mass spectrometry analysis of volatile compounds in raw meat for the
      authentication of the feeding background of farm animals.
AB  - The authentication of the conditions of animal production, based on the analysis
      of meat commercial cuts, is a major challenge on both societal and analytical
      grounds. The aim of the present work was to propose a method for the extraction
      of the volatile compounds from ruminant raw muscles trimmed of fat and to assess
      by mass spectrometry-based techniques the relevance of these compounds for the
      authentication of the type of feeding offered to the animals. The first step of
      the study consisted of validating conditions of dynamic headspace (DH) extraction
      of volatile compounds that enabled us to minimize the appearance of heat-induced
      artifacts and to maximize the richness of the DH-gas chromatography-mass
      spectrometry profile (DH-GC-MS) of raw lamb muscle. An extraction temperature of
      35 degrees C (vs 60 and 90 degrees C) and a sample mass of 6.25 g (vs 12.5, 25,
      and 50 g) were shown to be suitable. The second step aimed at identifying
      volatile compounds enabling us to discriminate muscle samples from 16
      experimental lambs fed either concentrate (n = 8) or pasture (n = 8). Before, to
      carefully explore the information given by the DH-GC-MS signal, the MS spectra
      acquired along the chromatogram were summed and then converted in a virtual-DH-MS
      spectral fingerprint to have a quick overview of the discriminative potential of
      the volatile fraction. According to univariate (analysis of variance) and to
      multivariate (principal component analysis) data treatments performed on virtual
      DH-MS fingerprints, the meat volatile fraction was relevant to reveal the type of
      feeding of the living animal. The detailed examination of the information given
      by the GC dimension showed that 33 volatile compounds among the 204 detected in
      the muscle by DH-GC-MS enabled us to discriminate the type of feeding of the
      lambs. The relevance of these results is discussed in light of previous studies
      performed on adipose tissues.

PMID- 17511465
TI  - Chemical composition and antioxidant activity of an acidic polysaccharide
      extracted from Cucurbita moschata Duchesne ex Poiret.
AB  - A simple and sensitive high-performance capillary electrophoresis (HPCE) method
      was designed for quantitative analysis of the component monosaccharides of an
      acidic polysaccharide extracted from pumpkin. In this method, the polysaccharide
      was hydrolyzed into component monosaccharides with 2.0 M trifluoroacetic acid at
      100 degrees C for 6 h and then labeled with 1-phenyl-3-methyl-5-pyrazolone, and
      subsequently the labeled monosaccharide derivatives were separated by HPCE. As a
      result, glucose (21.7%) and glucuronic acid (18.9%) were identified to be the
      main component monosaccharides, followed by galactose (11.5%), arabinose (9.8%),
      xylose (4.4%), and rhamnose (2.8%). Furthermore, the pumpkin polysaccharide was
      also demonstrated to effectively inhibit the H2O2-caused decrease of cell
      viability, lactate dehydrogenase leakage, and malondialdehyde formation, and also
      reduced the H2O2-caused decline of superoxide dismutase activity and glutathione
      depletion in cultured mouse peritoneal macrophages, indicating that pumpkin
      polysaccharide possessed significant cytoprotective effect and antioxidative
      activity.

PMID- 17511466
TI  - Assessment of the multi-mycotoxin-binding efficacy of a carbon/aluminosilicate
      based product in an in vitro gastrointestinal model.
AB  - A laboratory model, set to simulate the in vivo conditions of the porcine
      gastrointestinal tract, was used to study the small intestinal absorption of
      several mycotoxins and the effectiveness of Standard Q/FIS (a
      carbon/aluminosilicate-based product) in reducing mycotoxin absorption when added
      to multitoxin-contaminated diets. Mycotoxins were quickly absorbed in the
      proximal part of the small intestine at levels of 105 and 89% for fumonisins B1
      and B2, respectively, 87% for ochratoxin A, 74% for deoxynivalenol, 44% for
      aflatoxin B1, and 25% for zearalenone. Addition of Standard Q/FIS to the diet (up
      to 2%, w/w) significantly reduced mycotoxin absorption, in a dose-dependent
      manner, up to 88% for aflatoxin B1, 44% for zearalenone, and 29% for the
      fumonisins and ochratoxin. Standard Q/FIS was ineffective in reducing
      deoxynivalenol uptake. These findings suggest that Standard Q/FIS can be used as
      a multitoxin adsorbent material to prevent the individual and combined adverse
      effects of mycotoxins in animals.

PMID- 17511467
TI  - Oxalate in grain amaranth.
AB  - Grain amaranth (Amaranthus spp.) is a widely adaptable C4 pseudo-cereal crop that
      has interesting nutritional characteristics including high protein and calcium
      concentrations and a lack of gluten. To date, no antinutrient has been found at
      problematic levels in grain amaranth; however, oxalate has not been thoroughly
      studied. Dietary oxalate is a potential risk factor for kidney stone development,
      and its presence in food lowers calcium and magnesium availability. Oxalate
      concentration and forms and calcium and magnesium concentrations were determined
      in 30 field-grown grain amaranth genotypes from the species A. cruentus, A.
      hybrid, and A. hypochondriacus. The effects of seeding date and fertilization
      with calcium ammonium nitrate were evaluated in field experiments conducted in
      multiple environments; the effects of cooking were also evaluated. Mean total
      oxalate concentration in the 30 genotypes analyzed was 229 mg/100 g, with values
      ranging between 178 and 278 mg/100 g, the greatest proportion being insoluble
      (average of 80%). Calcium concentration averaged 186 mg/100 g and ranged between
      134 and 370 mg/100 g, whereas magnesium averaged 280 mg/100 g and ranged between
      230 and 387 mg/100 g. Fertilization only marginally increased total oxalate
      concentration and had no effects on other variables. Seeding date had no effects
      on any of the variables studied. Boiling increased the proportion of soluble
      oxalate but did not affect total oxalate concentration. Grain amaranth can be
      considered a high oxalate source, however, as most is in insoluble form, and due
      to its high calcium and magnesium concentrations, oxalate absorbability could be
      low. This should be confirmed by bioavailability studies.

PMID- 17511468
TI  - Fate of diuron and terbuthylazine in soils amended with two-phase olive oil mill
      waste.
AB  - The addition of organic amendments to soil increases soil organic matter content
      and stimulates soil microbial activity. Thus, processes affecting herbicide fate
      in the soil should be affected. The objective of this work was to investigate the
      effect of olive oil production industry organic waste (alperujo) on soil sorption
      desorption, degradation, and leaching of diuron [3-(3,4-dichlorophenyl)-1,1
      dimethylurea] and terbuthylazine [N2-tert-butyl-6-chloro-N4-ethyl-1,3,5-triazine
      2,4-diamine], two herbicides widely used in olive crops. The soils used in this
      study were a sandy soil and a silty clay soil from two different olive groves.
      The sandy soil was amended in the laboratory with fresh (uncomposted) alperujo at
      the rate of 10% w/w, and the silty clay soil was amended in the field with fresh
      alperujo at the rate of 256 kg per tree during 4 years and in the laboratory with
      fresh or composted alperujo. Sorption of both herbicides increased in laboratory
      amended soils as compared to unamended or field-amended soils, and this process
      was less reversible in laboratory-amended soils, except for diuron in amended
      sandy soil. Addition of alperujo to soils increased half-lives of the herbicides
      in most of the soils. Diuron and terbuthylazine leached through unamended sandy
      soil, but no herbicide was detected in laboratory-amended soil. Diuron did not
      leach through amended or unamended silty clay soil, whereas small amounts of
      terbuthylazine were detected in leachates from unamended soil. Despite their
      higher sorption capacity, greater amounts of terbuthylazine were found in the
      leachates from amended silty clay soils. The amounts of dissolved organic matter
      from alperujo and the degree of humification can affect sorption, degradation,
      and leaching of these two classes of herbicides in soils. It appears that adding
      alperujo to soil would not have adverse impacts on the behavior of herbicides in
      olive production.

PMID- 17511469
TI  - Acid-induced equilibrium folding intermediate of human platelet profilin.
AB  - The acid-induced unfolding of human platelet profilin (HPP) can be minimally
      modeled as a three-state process. Equilibrium unfolding studies have been
      performed on human platelet profilin1 (HPP) and monitored by far-UV circular
      dichroism, tryptophan fluorescence, ANS binding, and NMR spectroscopy. Far-UV CD
      measurements obtained by acid titration demonstrate that HPP unfolds via a three
      state mechanism (N --> I --> U), with a highly populated intermediate between pH
      4 and 5. Approximately 80% of native helical secondary structural content remains
      at pH 4, as indicated by monitoring the CD signal at 222 nm. The stability
      (DeltaGH2O) of the native conformation at pH 7.0 (obtained by monitoring the
      change in tryptophan signal as a function of urea concentration) is 5.56 +/- 0.51
      kcal mol-1; however, the DeltaGH2O for the intermediate species at pH 4 is 2.01
      +/- 0.47 kcal mol-1. The calculated m-values for the pH 7.0 and pH 4.0 species
      were 1.64 +/- 0.15 and 1.34 +/- 0.17 kcal mol-1 M-1, respectively, which is an
      indication that the native and intermediate species are similarly compact.
      Additionally, translational diffusion measurements obtained by NMR spectroscopy
      and ANS binding studies are consistent with a globular and compact conformation
      at both pH 7.0 and 4.0. The pKa values for the two histidine (His) residues
      located on helix 4 of HPP were determined to be 5.6 and 5.7 pH units. These pKa
      values coincide with the midpoint of the far-UV CD acid titration curve and
      suggest that the protonation of one or both His residues may play a role in the
      formation of the unfolding intermediate. Stable intermediate species populate the
      2D 1H-15N HSQC NMR spectra between pH 4 and 5. A number of backbone and side
      chain resonances show significant perturbations relative to the native spectrum;
      however, considerable nativelike tertiary contacts remain. Interestingly, the
      residues on HPP that are significantly altered at low pH coincide with segments
      of the G-actin binding surface and poly-l-proline binding interface. The earlier
      reports that a decrease in pH below 6.0 induces structural alterations in
      profilin, favoring dissociation of the profilin-actin complex, corresponds with
      the structural alterations observed in the partially unfolded species. Our
      findings suggest that a novel mechanism for pH induced disruption of the profilin
      G-actin complex involve a nativelike unfolding intermediate of profilin.

PMID- 17511471
TI  - Site-directed mutagenesis of UDP-galactopyranose mutase reveals a critical role
      for the active-site, conserved arginine residues.
AB  - The flavoenzyme UDP-galactopyranose mutase (UGM) is a mediator of cell wall
      biosynthesis in many pathogenic microorganisms. UGM catalyzes a unique ring
      contraction reaction that results in the conversion of UDP-galactopyranose (UDP
      Galp) to UDP-galactofuranose (UDP-Galf). UDP-Galf is an essential precursor to
      the galactofuranose residues found in many different cell wall glycoconjugates.
      Due to the important consequences of UGM catalysis, structural and biochemical
      studies are needed to elucidate the mechanism and identify the key residues
      involved. Here, we report the results of site-directed mutagenesis studies on the
      absolutely conserved residues in the putative active site cleft. By generating
      variants of the UGM from Klebsiella pneumoniae, we have identified two arginine
      residues that play critical catalytic roles (alanine substitution abolishes
      detectable activity). These residues also have a profound effect on the binding
      of a fluorescent UDP derivative that inhibits UGM, suggesting that the Arg
      variants are defective in their ability to bind substrate. One of the residues,
      Arg280, is located in the putative active site, but, surprisingly, the structural
      studies conducted to date suggest that Arg174 is not. Molecular dynamics
      simulations indicate that closed UGM conformations can be accessed in which this
      residue contacts the pyrophosphoryl group of the UDP-Gal substrates. These
      results provide strong evidence that the mobile loop, noted in all the reported
      crystal structures, must move in order for UGM to bind its UDP-galactose
      substrate.

PMID- 17511470
TI  - Domain orientation in the inactive response regulator Mycobacterium tuberculosis
      MtrA provides a barrier to activation.
AB  - The structure of MtrA, an essential gene product for the human pathogen
      Mycobacterium tuberculosis, has been solved to a resolution of 2.1 A. MtrA is a
      member of the OmpR/PhoB family of response regulators and represents the fourth
      family member for which a structure of the protein in its inactive state has been
      determined. As is true for all OmpR/PhoB family members, MtrA possesses an N
      terminal regulatory domain and a C-terminal winged helix-turn-helix DNA-binding
      domain, with phosphorylation of the regulatory domain modulating the activity of
      the protein. In the inactive form of MtrA, these two domains form an extensive
      interface that is composed of the alpha4-beta5-alpha5 face of the regulatory
      domain and the C-terminal end of the positioning helix, the trans-activation
      loop, and the recognition helix of the DNA-binding domain. This domain
      orientation suggests a mechanism of mutual inhibition by the two domains.
      Activation of MtrA would require a disruption of this interface to allow the
      alpha4-beta5-alpha5 face of the regulatory domain to form the intermolecule
      interactions that are associated with the active state and to allow the
      recognition helix to interact with DNA. Furthermore, the interface appears to
      stabilize the inactive conformation of MtrA, potentially reducing the rate of
      phosphorylation of the N-terminal domain. This combination of effects may form a
      switch, regulating the activity of MtrA. The domain orientation exhibited by MtrA
      also provides a rationale for the variation in linker length that is observed
      within the OmpR/PhoB family of response regulators.

PMID- 17511472
TI  - Cloning and molecular characterization of three arylamine N-acetyltransferase
      genes from Bacillus anthracis: identification of unusual enzymatic properties and
      their contribution to sulfamethoxazole resistance.
AB  - The arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes
      that catalyze the N-acetylation of arylamines and their N-hydroxylated
      metabolites. These enzymes play a key role in detoxication of numerous drugs and
      xenobiotics. We report here the cloning, functional expression, and
      characterization of three new NAT genes (termed banatA, banatB, and banatC) from
      the pathogen Bacillus anthracis. The sequences of the corresponding proteins are
      approximately 30% identical with those of characterized eukaryotic and
      prokaryotic NAT enzymes, and the proteins were recognized by an anti-NAT
      antibody. The three genes were endogenously expressed in B. anthracis, and NAT
      activity was found in cell extracts. The three NAT homologues exhibited distinct
      structural and enzymatic properties, some of which have not previously been
      observed with other NAT enzymes. Recombinant BanatC displayed strong NAT activity
      toward several prototypic NAT substrates, including the sulfonamide antibiotic
      sulfamethoxazole (SMX). As opposed to BanatC, BanatB also had acetyl-CoA (AcCoA)
      and p-nitrophenyl acetate (PNPA) hydrolysis activity in the absence of arylamine
      substrates, indicating that it may act as an AcCoA hydrolase. BanatA was devoid
      of NAT or AcCoA/PNPA hydrolysis activities, suggesting that it may be a new
      bacterial NAT-like protein with unknown function. Expression of BanatC in
      Escherichia coli afforded higher-than-normal resistance to SMX in the recombinant
      bacteria, whereas an inactive mutant of the enzyme did not. These data indicate
      that BanatC could contribute to the resistance of B. anthracis to SMX.

PMID- 17511473
TI  - Structure of the Na,K-ATPase regulatory protein FXYD1 in micelles.
AB  - FXYD1 is a major regulatory subunit of the Na,K-ATPase and the principal
      substrate of hormone-regulated phosphorylation by c-AMP dependent protein kinases
      A and C in heart and skeletal muscle sarcolemma. It is a member of an
      evolutionarily conserved family of membrane proteins that regulate the function
      of the enzyme complex in a tissue-specific and physiological-state-specific
      manner. Here, we present the three-dimensional structure of FXYD1 determined in
      micelles by NMR spectroscopy. Structure determination was made possible by
      measuring residual dipolar couplings in weakly oriented micelle samples of the
      protein. This allowed us to obtain the relative orientations of the helical
      segments and information about the protein dynamics. The structural analysis was
      further facilitated by the inclusion of distance restraints, obtained from
      paramagnetic spin label relaxation enhancements, and by refinement with a micelle
      depth restraint, derived from paramagnetic Mn line broadening effects. The
      structure of FXYD1 provides the foundation for understanding its intra-membrane
      association with the Na,K-ATPase alpha subunit and suggests a mechanism whereby
      the phosphorylation of conserved Ser residues, by protein kinases A and C, could
      induce a conformational change in the cytoplasmic domain of the protein to
      modulate its interaction with the alpha subunit.

PMID- 17511474
TI  - Mechanistic analysis of a suicide inactivator of histone demethylase LSD1.
AB  - Lysine-specific demethylase 1 (LSD1) is a transcriptional repressor and a flavin
      dependent amine oxidase that is responsible for the removal of methyl from lysine
      4 of histone H3. In this study, we characterize the mechanism and scope of LSD1
      inhibition by a propargylamine-derivatized histone H3 substrate (1). Unlike
      aziridinyl and cyclopropylamine-derivatized histone H3 peptide substrate
      analogues, compound 1 appears to covalently modify and irreversibly inactivate
      LSD1 with high potency. Accompanying this inactivation is a spectroscopic change,
      which shifts the absorbance maximum to 392 nm. Spectral changes associated with
      the 1-LSD1 complex and reactivity to decreased pH and sodium borohydride
      treatment were suggestive of a structure involving a flavin-linked inhibitor
      conjugate between N5 of the flavin and the terminal carbon of the inhibitor.
      Using a 13C-labeled inhibitor, NMR analysis of the 1-flavin conjugate was
      consistent with this structural assignment. Kinetic analysis of the spectroscopic
      shift induced by 1 showed that the flavin adduct formed in a reaction with
      kinetic constants similar to those of the LSD1 inactivation process. Taken
      together, these data support a mechanism of LSD1 inactivation by 1 involving
      amine oxidation followed by Michael addition to the propargylic imine. We further
      examined the potential for a biotinylated analogue of 1 (1-Btn) to be used as a
      tool in affinity pulldown experiments. Using 1-Btn, it was feasible to
      selectively pull down spiked and endogenous LSD1 from HeLa cell nuclear extracts,
      setting the stage for activity-based demethylase proteomics.

PMID- 17511475
TI  - Redox-regulated conformational changes in an SH3 domain.
AB  - Oxidation-induced conformational changes in proteins provide a powerful mechanism
      to sense the redox state of a living cell. In contrast to the unspecific and
      often irreversible oxidation of intracellular proteins during severe oxidative
      stress, regulatory redox events need to have specific and transient effects on
      cellular targets. Here we present evidence for the reversible formation of a
      vicinal disulfide bond in a prototypic protein interaction domain. NMR
      spectroscopy was used to determine the structure of the N-terminal hSH3 domain
      (hSH3N) of the immune cell protein ADAP (adhesion and degranulation promoting
      adapter protein) in the reduced and oxidized states. An eight-membered ring
      formed upon oxidation of two neighboring cysteines leads to significant changes
      in the variable arginine-threonine (RT) loop of the hSH3N domain and alters the
      helix-sheet packing of the domain. The redox potential for this structural
      transition is -228 mV at pH 7.4. This is compatible with a role of the
      cysteinylcysteine moiety in redox signaling during T cell activation.

PMID- 17511476
TI  - Intramolecular interaction between the DEP domain of RGS7 and the Gbeta5 subunit.
AB  - The R7 family of RGS proteins (RGS6, -7, -9, -11) is characterized by the
      presence of three domains: DEP, GGL, and RGS. The RGS domain interacts with
      Galpha subunits and exhibits GAP activity. The GGL domain permanently associates
      with Gbeta5. The DEP domain interacts with the membrane anchoring protein, R7BP.
      Here we provide evidence for a novel interaction within this complex: between the
      DEP domain and Gbeta5. GST fusion of the RGS7 DEP domain (GST-R7DEP) binds to
      both native and recombinant Gbeta5-RGS7, recombinant Gbetagamma complexes, and
      monomeric Gbeta5 and Gbeta1 subunits. Co-immunoprecipitation and FRET assays
      supported the GST pull-down experiments. GST-R7DEP reduced FRET between CFP
      Gbeta5 and YFP-RGS7, indicating that the DEP-Gbeta5 interaction is dynamic. In
      transfected cells, R7BP had no effect on the Gbeta5/RGS7 pull down by GST-R7DEP.
      The DEP domain of RGS9 did not bind to Gbeta5. Substitution of RGS7 Glu-73 and
      Asp-74 for the corresponding Ser and Gly residues (ED/SG mutation) of RGS9
      diminished the DEP-Gbeta5 interaction. In the absence of R7BP both the wild-type
      RGS7 and the ED/SG mutant attenuated muscarinic M3 receptor-mediated Ca2+
      mobilization. In the presence of R7BP, wild-type RGS7 lost this inhibitory
      activity, whereas the ED/SG mutant remained active. Taken together, our results
      are consistent with the following model. The Gbeta5-RGS7 molecule can exist in
      two conformations: "closed" and "open", when the DEP domain and Gbeta5 subunit
      either do or do not interact. The closed conformation appears to be less active
      with respect to its effect on Gq-mediated signaling than the open conformation.

PMID- 17511477
TI  - Allosteric effect of ATP on Na(+),K(+)-ATPase conformational kinetics.
AB  - The kinetics of the E2 --> E1 conformational change of unphosphorylated Na+,K+
      ATPase was investigated via the stopped-flow technique using the fluorescent
      label RH421 (pH 7.4, 24 degrees C). The enzyme was pre-equilibrated in a solution
      containing 25 mM histidine and 0.1 mM EDTA to stabilize the E2 conformation. When
      rabbit enzyme was mixed with 130 mM NaCl alone or with 130 mM NaCl and varying
      concentrations of Na2ATP simultaneously, a fluorescence decrease was observed. In
      the absence of ATP, the fluorescence decrease followed a biexponential time
      course, but at ATP concentrations after mixing of >or=50 microM, the fluorescence
      transient could be adequately fitted by a single exponential. On the basis of the
      agreement between theoretical simulations and experimental traces, we propose
      that in the absence of bound ATP the conformational transition occurs as a two
      step reversible process within a protein dimer, E2:E2 --> E2:E1 --> E1:E1. In the
      presence of 130 mM NaCl, the sum of the forward and backward rate constants for
      the E2:E2 --> E2:E1 and E2:E1 --> E1:E1 transitions were found to be 10.4 (+/
      1.0) and 0.49 (+/-0.02) s-1, respectively. At saturating concentrations of ATP,
      however, the transition occurs in a single reversible step with the sum of its
      forward and backward rate constants equal to 35.2 (+/-0.3) s-1. It was found that
      ATP acting at a high affinity site (Kd approximately 0.25 microM), stimulated the
      reverse reaction, E1ATP --> E2ATP, in addition to its known allosteric low
      affinity (Kd approximately 71 microM) stimulation of the forward reaction, E2ATP 
      -> E1ATP.

PMID- 17511479
TI  - Metabolic epoxidation of an alpha,beta-unsaturated oxime generates sensitizers of
      extreme potency. Are nitroso intermediates responsible?
AB  - Metabolic activation of inherently nonprotein-reactive compounds (prohaptens) in
      the skin can lead to development of contact allergy, a chronic skin disease. The
      prohapten hypothesis has existed for more than 20 years; yet, detailed knowledge
      regarding the mechanisms of activation as well as what structural moieties can be
      transformed to protein-reactive sensitizers is still limited. Today, the
      consideration of cutaneous bioactivation is important when developing nonanimal
      based assays for prediction of contact allergenic activity, as only methods that
      include skin metabolism are able to detect prohaptens as sensitizers. We have
      studied the mechanism of activation of the prohapten carvoxime (1), a strongly
      sensitizing but in itself poorly protein-reactive alpha,beta-unsaturated oxime.
      alpha,beta-Unsaturated oximes represent a novel class of prohaptens, which
      previously have never been investigated for potential metabolic activation. To
      identify reactive metabolites formed from 1, liver microsomal incubations in the
      presence of glutathione were carried out. Putative reactive metabolites were
      synthesized, and their allergenic activity, chemical reactivity toward
      nucleophiles, and ability to elicit a contact allergenic response in animals
      induced with 1 were assessed. We found that 1 is metabolically activated by
      epoxidation of the allylic carbon-carbon double bond. The alpha,beta-epoxy oxime
      metabolites were found to be sensitizers of extreme potency in the local lymph
      node assay and highly reactive toward nucleophilic amino acids and a model
      peptide. One of the two diastereomeric epoxy metabolites also elicited an
      allergic reaction in mice sensitized to 1, in the mouse ear swelling test.
      Furthermore, this study presents strong indications that the basis of the high
      reactivity and sensitizing capacity observed for the alpha,beta-unsaturated
      oximes is related to their ability to form highly reactive nitroso intermediates
      by tautomerization. To our knowledge, the formation of nitrosoalkenes by
      oxidative metabolism of alpha,beta-unsaturated oximes has not been shown so far.

PMID- 17511480
TI  - Structure evolution in layers of polymer blend nanoparticles.
AB  - The early stages of phase evolution, not available for nanometer polymer blend
      films spin-cast from solutions of incompatible mixtures, have been examined for
      films prepared from nanoparticles of deuterated polystyrene/ poly(methyl
      methacrylate) blends (1:1 mass fraction of dPS/PMMA) with PS-PMMA diblock
      copolymer additives. The initial phase arrangement, confined to the size of
      nanoparticles, has provided the homogeneity of the initial film composition. The
      early stages of structure formation, promoted by annealing and traced with atomic
      and lateral force microscopy (AFM, LFM) as well as secondary ion mass
      spectroscopy (SIMS), resulted in bilayers, observed commonly for as-prepared
      solvent-cast blends. The initiated capillary instability of the upper dPS-rich
      layer depended on copolymer additives, which enhanced the lateral structures
      pinning the dewetting process.

PMID- 17511481
TI  - Adhesion enhancement through micropatterning at polydimethylsiloxane-acrylic
      adhesive interfaces.
AB  - Adhesion at polydimethylsiloxane (PDMS)-acrylic adhesive interfaces is shown to
      be enhanced through micropatterning of the PDMS substrate. By varying the
      geometry of the patterns (groves and hexagonal arrays of pillars of micrometer
      sizes, obtained through soft lithography techniques) and comparing rigid and
      deformable substrates, the respective roles of the geometry and the size and
      flexibility of the pattern features on the level of adhesion have been analyzed.
      For cylindrical pillars, two regimes are clearly identified: for a relatively low
      aspect ratio (h/r < 3, with h and r, respectively, the height and the radius of
      the pillars), soft patterned substrates are more efficient than rigid ones at
      increasing adhesion, pointing out the role of the elastic energy associated with
      the deformation of the pattern that is lost when the adhesive detaches from the
      substrate. Using scaling laws, the predominant contribution to that elastic
      energy can be further identified: deformation of the substrate underlying the
      pillars for h/r < 1.6 or bending of the pillars for h/r > 1.6.; for a high aspect
      ratio (h/r > 3), only rigid patterned substrates enhance adhesion, then the only
      possible contribution to energy dissipation comes from the enhanced viscoelastic
      losses associated with the pattern that induce modifications of the strain field
      within the adhesive layer. Soft, high aspect ratio patterns lose their efficiency
      even if still bent under the effect of the peel forces. This is because when
      bent, some of the pillars touch each other and remain stuck together, lying flat
      on the surface after the passage of the peel front. The bending elastic energy of
      the pillars (which is still lost) is then balanced by the corresponding gain in
      surface energy of the substrate in the peeled region. These systematic
      experiments demonstrate that the ability of the patterned surface to be deformed
      plays a crucial role in enhancing adhesion and allow us to propose a way to fine
      tune the level of adhesion at PDMS-acrylic adhesive interfaces, independently of
      the chemistry of the adhesive.

PMID- 17511482
TI  - A case for discotic liquid crystals in molten triglycerides.
AB  - To date, essentially only two structural models have been proposed and debated in
      detail for explaining the liquid state order of triglycerides, and both invoke a
      form of thermotropic liquid crystalline order in triglyceride melts. These are
      the paralamellar model of Larsson et al. (J. Am. Oil Chem. Soc. 1992, 69, 835)
      and the nematic model of Cebula et al. (J. Am. Oil Chem Soc. 1992, 69, 130). An
      alternative discotic model is proposed here that adequately accounts for the
      broad small-angle X-ray diffraction peak often observed in the liquid state of
      fats and oils. In this alternative model, triglyceride molecules exist in the
      liquid state with fully splayed chains, approximating "Y"-shapes (Y-conformers).
      These are loosely bound within discs that stack into flexible, relatively short
      cylindrical rods of colloidal dimension, which in turn assemble into rod-packings
      with short-range order akin to disordered versions of thermotropic discotic
      liquid crystalline phases in other lipidic systems.

PMID- 17511483
TI  - Salt effect on the nanostructure of strong polyelectrolyte brushes in amphiphilic
      diblock copolymer monolayers on the water surface.
AB  - The nanostructure of a spread monolayer of diblock copolymers of
      poly(hydrogenated isoprene) and poly(styrenesulfonate) at the air/water interface
      were studied by in situ X-ray reflectivity as a function of the brush density and
      salt concentration. When the monolayer was compressed beyond the "critical brush
      density", its nanostructure changed from a flat, adsorbed "carpet" layer to a
      "carpet + brush" structure. The critical brush density was found to be about 0.12
      nm-2, independent the brush length and salt concentration under a low-salt
      condition. The brush formation behavior was considered to be controlled by an
      electrostatic interaction between polyelectrolyte chains rather than by a steric
      hindrance. This might be because the distance between the chains at the critical
      point is rather long and also because of the effect of the salt on the critical
      brush density. The critical brush density increased at higher added salt
      concentration beyond 1 M. As a result, we found a new structure transition
      behavior of the polymer brushes between carpet-only and carpet + brush
      structures, which was induced by salt addition. Finally, we succeeded in the
      controlled release of salt ions from the salted brush layer by changing the brush
      density by compression of the monolayer.

PMID- 17511484
TI  - Templated assembly of biomembranes on silica microspheres using bacteriorhodopsin
      conjugates as structural anchors.
AB  - Membrane proteins are some of the most sophisticated molecules found in nature.
      These molecules have extraordinary recognition properties; hence, they represent
      a vast source of specialized materials with potential uses in sensing and
      screening applications. However, the strict requirement of the native lipid
      environment to preserve their structure and functionality presents an impediment
      in building biofunctional materials from these molecules. In general, the
      purification protocols remove the native lipid support structures found in the
      cellular environment that stabilize the membrane proteins. Furthermore, the
      membrane protein structure is often highly complex, typified by large,
      multisubunit complexes that not only span the lipid bilayer but also contain
      large (>2 nm) cytoplasmic and extracellular domains that protrude from the
      membrane. The present study is focused on using a biomimetic approach to build a
      stable, fluid microenvironment to be used to incorporate larger membrane proteins
      of interest into a tether-supported lipid bilayer membrane adequately spaced
      above a substrate passivated to liposome fusion and nonspecific adsorption. Our
      aim is to reintroduce the supporting structures of the native cell membrane using
      self-assembled supramolecular complexes constructed on microspheres in an
      artificial cytoskeleton motif. Central to our architecture is to utilize
      bacteriorhodopsin (bR), a transmembrane protein, as a biomembrane anchoring
      molecule to be tethered to surfaces of interest as a sparse structural element in
      the design. Compared to a typical lipid tether, which inserts into one leaflet of
      the lipid bilayer, bR anchoring provides an over 8-fold greater hydrophobic
      surface area in contact with the bilayer. In the work presented here, the silica
      microsphere surface was biofunctionalized with streptavidin to make it a suitable
      supporting interface. This was achieved by self-assembly of (p
      aminophenyl)trimethoxysilane on the silica surface followed by subsequent
      conjugation of biotin-PEG3400 (PEG = poly(ethylene glycol) and PEG2000 for
      further passivation and the binding of streptavidin. We have conjugated bR with
      biotin-PEG3400 through amine-based coupling to use it as a tether. The biotin-PEG
      bR conjugate was further labeled with Texas Red to facilitate localization via
      fluorescence imaging. Confocal microscopy was utilized to analyze the microsphere
      surface at different stages of surface modification by employing fluorescent
      staining techniques. Sparely tethered supported lipid bilayer membranes were
      constructed successfully on streptavidin-functionalized silica particles (5 mum)
      using a detergent-based method in which tethered bR nucleates self-assembly of
      the bilayer membrane. The fluidity of the supported membranes was analyzed using
      fluorescence recovery after photobleaching in confocal imaging detection mode.
      The phospholipid diffusion coefficients obtained from these studies indicated
      that nativelike fluidity was achieved in the tether-supported membranes, thus
      providing a prospective microenvironment for insertion of membrane proteins of
      interest.

PMID- 17511485
TI  - Microfluidic hydrogen fuel cell with a liquid electrolyte.
AB  - We report the design and characterization of a microfluidic hydrogen fuel cell
      with a flowing sulfuric acid solution instead of a Nafion membrane as the
      electrolyte. We studied the effect of cell resistance, hydrogen and oxygen flow
      rates, and electrolyte flow rate on fuel cell performance to obtain a maximum
      power density of 191 mW/cm2. This flowing electrolyte design avoids water
      management issues, including cathode flooding and anode dry out. Placing a
      reference electrode in the outlet stream allows for independent analysis of the
      polarization losses on the anode and the cathode, thereby creating an elegant
      catalyst characterization and optimization tool.

PMID- 17511486
TI  - Fabrication of biomolecular nanostructures by scanning near-field
      photolithography of oligo(ethylene glycol)-terminated self-assembled monolayers.
AB  - The UV photo-oxidation of oligo(ethylene glycol) (OEG)-terminated self-assembled
      monolayers (SAMs) has been studied using static secondary ion mass spectrometry,
      X-ray photoelectron spectroscopy, contact angle measurement, and friction force
      microscopy. OEG-terminated SAMs are oxidized to yield sulfonates, but
      photodegradation of the OEG chain also occurs on a more rapid time scale,
      yielding degradation products that remain bound to the surface via gold-sulfur
      bonds. The oxidation of these degradation products is the rate-limiting step in
      the process. Photopatterning of OEG-terminated SAMs may be accomplished by using
      a mask and suitable light source or by using scanning near-field photolithography
      (SNP) in which the mask is replaced by a scanning near-field optical microscope
      coupled to a UV laser. Using SNP, it is possible to fabricate patterns in SAMs
      with a full width at half-maximum height (fwhm) as small as 9 nm, which is
      approximately 15 times smaller than the conventional diffraction limit. SNP
      patterned OEG-terminated SAMs may be used to fabricate protein nanopatterns. By
      adsorbing carboxylic acid-terminated thiols into oxidized regions and converting
      these to active ester intermediates, it has been possible to fabricate lines of
      protein molecules with widths of only a few tens of nanometers.

PMID- 17511487
TI  - Finely controlled size-selective precipitation and separation of CdSe/ZnS
      semiconductor nanocrystals using CO2-gas-expanded liquids.
AB  - A technique was developed to size-selectively separate polydisperse dispersions
      of CdSe/ZnS nanocrystals into distinct color fractions using only the tunable
      solvent properties of CO2-expanded hexane. This size-selective precipitation of
      semiconductor nanoparticles is achieved by finely tuning the solvent strength of
      the CO2/hexane medium by simply adjusting the applied CO2 pressure. These subtle
      changes affect the balance between osmotic repulsive and van der Waals attractive
      forces, thereby allowing fractionation of the nanocrystals into multiple narrow
      size populations.

PMID- 17511488
TI  - Monoglycerides and beta-lactoglobulin adsorbed films at the air-water interface.
      structure, microscopic imaging, and shear characteristics.
AB  - In this work we have analyzed the structural, topographical, and shear
      characteristics of mixed monolayers formed by adsorbed beta-lactoglobulin (beta
      lg) and spread monoglyceride (monopalmitin or monoolein) on a previously adsorbed
      protein film. Measurements of the surface pressure (pi)-area (A) isotherm,
      Brewster angle microscopy (BAM), and surface shear characteristics were obtained
      at 20 degrees C and at pH 7 in a modified Wilhelmy-type film balance. The pi-A
      isotherm and BAM images deduced for adsorbed beta-lactoglobulin-monoglyceride
      mixed films at pi lower than the equilibrium surface pressure of beta
      lactoglobulin (pi(e)(beta-lg)) indicate that beta-lactoglobulin and monoglyceride
      coexist at the interface. However, the interactions between protein and
      monoglyceride are somewhat weak. At higher surface pressures (at pi > or =
      pi(e)(beta-lg)) a protein displacement by the monoglyceride from the interface
      takes place. The surface shear viscosity (eta(s)) of mixed films is very
      sensitive to protein-monoglyceride interactions and displacement as a function of
      monolayer composition (protein/monoglyceride fraction) and surface pressure.
      Shear can induce change in the morphology of monoglyceride and beta-lactoglobulin
      domains, on the one hand, and segregation between domains of the film-forming
      components on the other hand. In addition, the displacement of beta-lactoglobulin
      by the monoglycerides is facilitated under shear conditions.

PMID- 17511489
TI  - Formation of tethered polyacrylic acid loops in core-shell micelles.
AB  - Well-defined amphiphilic four-arm star P(AA-b-STY) block copolymers have been
      dispersed in water to form core-shell micelles in which the shell consists of
      tethered PAA loops. The entropic penalty for having such loops resulted in a less
      densely packed PSTY core when compared to linear diblock copolymers of the same
      arm length. The surface of the shell is irregular because of the tethering
      points, but when cleaved the PAA chains extend to form a regular and relatively
      uniform corona.

PMID- 17511490
TI  - Titration of ionizable monolayers by measurement of the electric double-layer
      force.
AB  - We have determined the pKa of surface-bound primary amine groups by determining
      the surface potential as a function of solution pH from the magnitude of the
      electric double-layer force. Using colloid-probe atomic force microscopy (AFM),
      we measured the force as a function of separation between a particle of radius R
      = 10 microm and a planar surface, each coated with a self-assembled monolayer of
      HS(CH2)2CONH((CH2)2O)8(CH2)2NH2. The force was measured from pH 3 to 7, and the
      surface potential was determined by fitting the results to solutions of the
      nonlinear Poisson-Boltzmann equation. The surface pKa of the primary amine group
      was found to be 5.0 +/- 0.2, in agreement with the results of contact-angle and
      chemical-force titrations on similar surfaces with primary amine groups. The
      surface charge density indicates that less than 1% of the NH2 groups are
      dissociated at pH 3, suggesting that ionization is very unfavorable in the local
      environment of the ethylene oxide chains. This noncontact method should be of
      general applicability to surfaces with ionizable groups and avoids the possible
      complications of large contact forces on the surfaces under study.

PMID- 17511491
TI  - Use of lanthanide-grafted inorganic nanoparticles as effective contrast agents
      for cellular uptake imaging.
AB  - The improvement of commonly used Gd3+ -based MRI agents requires the design of
      new systems with optimized in vivo efficacy, pharmacokinetic properties, and
      specificity. To design these contrast agents, two parameters are usually
      considered: increasing the number of coordinated water molecules or increasing
      the rotational correlation time by increasing molecular weight and size. This has
      been achieved by noncovalent or covalent binding of low-molecular weight Gd3+
      chelates to macromolecules or polymers. The grafting of these high-spin
      paramagnetic gadolinium chelates on metal oxide nanoparticles (SiO2, Al2O3) is
      proposed. This new synthetic strategy presents at least two main advantages: (1)
      a high T1-relaxivity for MRI with a 275% increase of the MRI signal and (2) the
      ability of nanoparticles to be internalized in cells. Results indicate that these
      new contrast agents lead to a huge reconcentration of Gd3+ paramagnetic species
      inside microglial cells. This reconcentration phenomenon gives rise to high
      signal-to-noise ratios on MR images of cells after particle internalization, from
      1.4 to 3.75, using Al2O3 or SiO2 particles, respectively. The properties of these
      new particles will be further used to get new insight into gene therapy against
      glioma, using microglial cells as vehicles to simultaneously transport a suicide
      gene and contrast agents. Since microglia are chemoattracted to brain tumors, the
      presence of these new contrast agents inside the cells will lead to a better MRI
      determination of the in vivo location, shape, and borders of the tumors. These
      Gd3+-loaded microglia can therefore provide effective localization of tumors by
      MRI before applying any therapeutic treatment. The rate of carcinoma remission
      following a suicide gene strategy is also possible.

PMID- 17511493
TI  - Molecular dynamics simulations of methane hydrate using polarizable force fields.
AB  - Molecular dynamics simulations of methane hydrate have been carried out using the
      polarizable AMOEBA and COS/G2 force fields. Properties calculated include the
      temperature dependence of the lattice constant, the OC and OO radial distribution
      functions, and the vibrational spectra. Both the AMOEBA and COS/G2 force fields
      are found to successfully account for the available experimental data, with
      overall somewhat better agreement with experiment being found for the AMOEBA
      model. Comparison is made with previous results obtained using TIP4P and SPC/E
      effective two-body force fields and the polarizable TIP4P-FQ force field, which
      allows for in-plane polarization only. Significant differences are found between
      the properties calculated using the TIP4P-FQ model and those obtained using the
      other models, indicating an inadequacy of restricting explicit polarization to in
      plane only.

PMID- 17511492
TI  - Comparison of several linear fluorophore- and quencher-conjugated oligomer
      duplexes for stability, fluorescence quenching, and kinetics in vitro and in vivo
      in mice.
AB  - A useful property of optical imaging is the potential to modulate the detectable
      signal to improve target/nontarget ratios. When administered as a dimer of a
      fluorophore- and a quencher-conjugated duplex arranged to inhibit fluorescence
      but designed to dissociate only in the presence of its target, the fluorescence
      signal should in principle appear only in the target. This laboratory has
      demonstrated the feasibility of this approach by using a duplex consisting of a
      linear oligomer conjugated with Cy5.5 (emitter) hybridized to another linear
      oligomer conjugated with Iowa Black (quencher) in a pretargeting optical study.
      Now eight duplexes consisting of combinations of 18 mer linear phosphodiester
      (PO) and phosphorothioate (PS) DNAs and phosphorodiamidate morpholinos (MORFs)
      conjugated with Cy5.5 (emitter) and Iowa Black (quencher) were variously screened
      for in vitro duplex stability. The MORF/PO duplex was selected for further study
      based on evidence of stability in 37 degrees C serum. Simultaneously, the
      kinetics of quenching were investigated in vitro and in vivo in mice. Thereafter,
      mice were implanted in one thigh with MORF/PO Cy 5.5 microspheres and the
      complementary PS Iowa Black administered iv to measure the extent and kinetics of
      duplex formation in the target. While all duplexes were stable in buffer, only
      the MORF/PO duplexes and possibly all PS containing duplexes were stable in 37
      degrees C serum for at least 4 h. The kinetics of quenching were found to be
      rapid in vitro, with a 80-90% decrease in Cy5.5 fluorescence immediately
      following formation of a PS/PS homoduplex, and in vivo, with a 27 to 38% decrease
      in target thigh/nontarget ratio within 1 h following administration of the
      complementary PS Iowa Black complementary DNA but not the random control DNA to
      mice implanted with MORF/PO Cy5.5 microspheres. This investigation has provided
      additional evidence that Cy5.5 may be efficiently and rapidly quenched by Iowa
      Black when both are conjugated to complementary oligomers and that the resulting
      inhibition of fluorescence is sufficiently persistent for imaging.

PMID- 17511494
TI  - Fabrication of organic thin-film transistors using layer-by-layer assembly.
AB  - Layer-by-layer assembly is presented as a deposition technique for the
      incorporation of ultrathin gate dielectric layers into thin-film transistors
      utilizing a highly doped organic active layer. This deposition technique enables
      the fabrication of device structures with a controllable gate dielectric
      thickness. In particular, devices with a dielectric layer comprised of
      poly(allylamine hydrochloride)/poly(acrylic acid) (PAH/PAA) bilayer films were
      fabricated to examine the properties of poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) as the transistor
      active layer. The transistor Ion/off ratio and switching speed are shown to be
      controlled by the gate bias, which is dependent upon the voltage applied and the
      number of bilayers deposited for the gate dielectric. The devices operate in the
      depletion mode as a result of dedoping of the active layer with the application
      of a positive gate bias. The depletion and recovery rate are highly dependent on
      the level of hydration in the film and the environment under which the device is
      operated. These observations are consistent with an electrochemical dedoping of
      the conducting polymer during operation.

PMID- 17511495
TI  - Theoretical investigation of the binding of small molecules and the
      intramolecular agostic interaction at tungsten centers with carbonyl and
      phosphine ligands.
AB  - The factors controlling both the binding of small molecules to several tungsten
      complexes and agostic bonding in the W(CO)3(PCy3)2 complex have been examined
      through B3LYP hybrid density functional theory and ab initio MP2 calculations
      with and without basis set superposition error (BSSE) corrections. This approach
      attempts to isolate insofar as possible the separate effects of intrinsic bonding
      interactions, electron induction by ligands, and steric hindrance and strain. An
      important conclusion from this study is that for bimolecular reactions, BSSE
      corrections must be included for quantitative predictions. There is a reasonably
      good correlation between the BSSE-corrected B3LYP and MP2 results for bond
      dissociation enthalpies (BDEs) of very small molecules (H2, N2, and CO), but
      generally B3LYP BDEs tend to be smaller than the corresponding MP2 values. In the
      few cases where a comparison with experimental data can be appropriately made, it
      appears that the BSSE-corrected MP2 BDEs are more reliable. Using N2 as a probe
      molecule, the strength of the agostic bond in W(CO)3(PCy3)2 has been examined by
      calculating the BDE of N2 in a series of tungsten complexes with increasing
      electron inducing effect without agostic bonding, then extrapolating the expected
      trend to the case of agostically bonded W(CO)3(PCy3)2. Comparison of the
      extrapolated value to the calculated BDE of W(CO)3(PCy3)2(N2) yields an estimated
      strength of the agostic bond of from 7 to 9 kcal mol-1. Approximately 5 kcal mol
      1 of the interaction is assigned to the net agostic interaction associated with
      moving from a nonagostic local minimum configuration of the PCy3 ligands to the
      agostically bonded global minimum.

PMID- 17511497
TI  - Use of spectra resolution methodology to investigate surfactant/beta-cyclodextrin
      mixed systems.
AB  - A study of the spectral behavior of crystal violet in mixed systems formed by
      hexadecyltrimethylammonium chloride (CTACl) and beta-cyclodextrin (beta-CD) has
      been carried out. The spectra resolution methodology was used to decompose the
      absorption spectra of crystal violet in the sum of constituent sub-bands centered
      at 17,953, 16,807, and 16,474 cm(-1). The sub-bands centered at upsilon = 17,953
      and 16,807 cm(-1) correspond to planar and pyramidal isomers of the dye in water
      and the same isomers associated with the cyclodextrin and micelle. The sub-band
      centered at upsilon = 16,474 cm(-1) is due to the formation of an inclusion
      complex between the dye and the cyclodextrin, where solvation of the carbocation
      takes place through the hydroxyl groups of the cyclodextrin and the association
      of the crystal violet to micelles of CTACl through the formation of ion pairs in
      the Stern layer. The results obtained in the mixed systems are compatible with
      the results obtained in the previously studied simple systems, thus supporting
      the situation where interactions do not exist between cyclodextrins and micelles
      once these have formed.

PMID- 17511496
TI  - Deduction of structural information of interfacial proteins by combined
      vibrational spectroscopic methods.
AB  - We demonstrate both theoretically and experimentally that the combination of
      vibrational spectroscopic techniques on samples can be used to deduce more
      detailed structural information of interfacial proteins and peptides. Such an
      approach can be used to elucidate structures of proteins or peptides at
      interfaces, such as at the solid/liquid interface or in cell membranes. We also
      discuss that the controlled perturbations may provide more measured parameters
      for structural studies on such proteins and peptides. In this paper, we will
      demonstrate that optical spectroscopic techniques such as polarized Fourier
      transform infrared spectroscopy (FTIR), sum frequency generation (SFG)
      vibrational spectroscopy, and higher order nonlinear vibrational spectroscopies
      can be used to deduce different and complementary structural information of
      molecules at interfaces (e.g., orientation information of certain functional
      groups and secondary structures of interfacial proteins). Also, we believe that
      controlled perturbations on samples, such as variation of sample temperature,
      application of electrical fields, and alternation of substrate roughness, can
      provide more detailed information regarding the interfacial structures of
      proteins and peptides. The development of nonlinear vibrational spectroscopies,
      such as SFG and four-wave mixing vibrational spectroscopy, to examine interfacial
      protein and peptide structures, and introduction of external perturbations on
      samples should be able to substantially advance our knowledge in understanding
      structures and thus functions of proteins and peptides at interfaces.

PMID- 17511498
TI  - A minimalist model for exploring conformational effects on the electrospray
      charge state distribution of proteins.
AB  - The electrospray ionization (ESI) charge state distribution of proteins is highly
      sensitive to the protein structure in solution. Unfolded conformations generally
      form higher charge states than tightly folded structures. The current study
      employs a minimalist molecular dynamics model for simulating the final stages of
      the ESI process in order to gain insights into the physical reasons underlying
      this empirical relationship. The protein is described as a string of 27 beads
      ("residues"), 9 of which are negatively charged and represent possible
      protonation sites. The unfolded state of this bead string is a random coil,
      whereas the native conformation adopts a compact fold. The ESI process is
      simulated by placing the protein inside a solvent droplet with a 2.5 nm radius
      consisting of 1600 Lennard-Jones particles. In addition, the droplet contains 14
      protons which are modeled as highly mobile point charges. Disintegration of the
      droplet rapidly releases the protein into the gas phase, resulting in average
      charge states of 4.8+ and 7.4+ for the folded and unfolded conformation,
      respectively. The protonation probabilities of individual residues in the folded
      state reveal a characteristic pattern, with values ranging from 0.2 to 0.8. In
      contrast, the protonation probabilities of the unfolded protein are more uniform
      and cover the range from 0.8 to 1.0. The origin of these differences can be
      traced back to a combination of steric and electrostatic effects. Residues
      exhibiting a small accessible surface area are less likely to capture a proton,
      an effect that is exacerbated by partial electrostatic shielding from nearby
      positive residues. Conversely, sites that are sterically exposed are associated
      with electrostatic funnels that greatly increase the likelihood of protonation.
      Unfolding enhances the steric and electrostatic exposure of protonation sites,
      thereby causing the protein to capture a greater number of protons during the
      droplet disintegration process.

PMID- 17511500
TI  - Formation of a novel heparin-based hydrogel in the presence of heparin-binding
      biomolecules.
AB  - An injectable, heparin-based hydrogel system with the potential to be gelled with
      cells was developed. First, heparin was modified to have thiol groups by the
      modification of carboxylic groups of heparin with cysteamine using carbodiimide
      chemistry. Thiol functionalization of heparin carboxylic groups was controlled
      from 10% to 60% of the available COOH groups, and the retained bioactivity of the
      modified heparin, characterized by its binding affinity to antithrombin III,
      decreased with increasing functionalization. Then, the thiol-functionalized
      heparin was reacted with poly(ethylene glycol) diacrylate to form a hydrogel. The
      gelation kinetics and mechanical properties of the final gel state could be tuned
      by controlling cross-link density. Fibroblast cell encapsulation using this
      hydrogel revealed the nontoxicity of the present system. Cell proliferation
      inside the hydrogel was observed, and it was significantly enhanced (more than 5
      fold) by the addition of fibrinogen into the hydrogel during gelation.

PMID- 17511499
TI  - Antibacterial activities of poly(amidoamine) dendrimers terminated with amino and
      poly(ethylene glycol) groups.
AB  - Poly(amidoamine) (PAMAM) dendrimer derivatives have been investigated for their
      biological applications, especially for delivery of drugs, including
      antimicrobial drugs to eukaryotic cells, but their effects on bacterial cells are
      largely unexplored. Herein we report that amino-terminated PAMAM dendrimers are
      highly toxic to the common Gram-negative pathogen Pseudomonas aeruginosa. The
      concentration that kills 50% of the bacteria (EC50) was in the range of
      approximately 0.9-1.5 microg/mL for the generation 5, amino-terminated dendrimers
      with or without partial (43%) coating of poly(ethylene glycol) (PEG). These EC50
      values were lower than that ( approximately 1.9-2.8 microg/mL) for LL-37, a
      potent antimicrobial peptide expressed in a variety of epithelia. On the
      contrary, the dendrimers were far less toxic (EC50 > 21 microg/mL) to the Gram
      positive pathogen Staphylococcus aureus than LL-37 (EC50 = approximately 1.9
      microg/mL). In agreement with the previous studies on other cell types, the
      dendrimers were not cytotoxic to human corneal epithelial cells at the
      concentrations that were toxic to P. aeruginosa. Our findings indicate that amino
      terminated PAMAM dendrimers and their partially PEG-coated derivatives possess
      attractive antimicrobial properties, particularly against Gram-negative bacteria,
      thus expanding the potential biological application of the dendrimers.

PMID- 17511501
TI  - Encapsulation of paclitaxel in macromolecular nanoshells.
AB  - An electrostatic layer-by-layer self-assembly technique was used to encapsulate
      solid core paclitaxel nanoparticles within a polymeric nanometer-scale shell.
      This approach provides a new strategy for the development of polymeric vehicles
      that control drug release and target diseased tissues and cells specific to the
      ailment, such as breast cancer. Core paclitaxel nanoparticles, 153 +/- 28 nm in
      diameter, were prepared using a modified nanoprecipitation technique. A nanoshell
      composed of multilayered polyelectrolytes, poly(allylamine hydrochloride) and
      poly(styrene-4-sulfonate) was assembled stepwise onto core charged drug
      nanoparticles. In vitro studies were performed to determine the anticancer
      activity of paclitaxel core-shell nanoparticles. Paclitaxel core-shell
      nanoparticles induced cell cycle arrest in the G2/M phase after 24 and 48 h of
      incubation with a human breast carcinoma cell line, MCF-7. Changes in MCF-7 cell
      morphology, fragmentation of the nucleus, and loss of cell-cell contacts
      indicated that the cells responded to paclitaxel core nanoparticles upon
      treatment for 24 and 48 h. Cells arrested in G2/M phase illustrated abnormal
      microtubule and actin cytoskeleton morphology. The core-shell drug nanoparticles
      fabricated using this procedure provide a new approach in the delivery of
      paclitaxel devoid of Cremophor EL, a solvent that causes adverse side effects in
      patients undergoing chemotherapy for treatment of metastasized mammary cancers.

PMID- 17511502
TI  - Chemical modification of wheat-protein-based natural polymers: formation of
      polymer networks with alkoxysilanes to modify molecular motions and enhance the
      material performance.
AB  - The mechanical performance of plasticized wheat gluten (WG) materials was
      significantly modified through the formation of different chemical and network
      structures with alkoxysilanes. The epoxy-functionalized alkoxysilanes were
      grafted to segments of WG, and then the condensation reactions between
      alkoxysilane segments occurred during thermal processing to form WG-siloxane
      networks. The mechanical properties and molecular motions of the networks were
      dependent on the amount and type of alkoxysilanes applied. A lower amount of
      alkoxysilanes caused the alkoxysilane molecules to predominately graft onto WG
      chains without forming linkages between WG segments, which produced an additional
      plasticizing effect on the WG systems with a longer elongation value and weaker
      tensile strength at relative humidity (RH) = 50% as compared to the WG system.
      However, such grafting improved the hydrostability of the materials and generated
      an improvement in tensile strength at RH = 85%. Increasing the amount of
      alkoxysilanes in the systems led to the formation of cross-linked WG-siloxane
      networks via linkages between alkoxysilane segments. Remarkable strength
      improvement was obtained for the networks with elongation values still higher
      than the original plasticized WG due to the flexible nature of the siloxane
      components. A more significant strength improvement was obtained for the WG-SiA
      systems at both RH = 50% and 85%, where SiA could form three-dimensional networks
      from siloxane condensation and generate highly cross-linked network structures
      with relatively low mobility. For WG-SiB systems, SiB could only form linear
      linkages, and the higher mobility of the SiB phase caused the systems to display
      a lower strength improvement with a longer elongation value.

PMID- 17511503
TI  - Cyathusals A, B, and C, antioxidants from the fermented mushroom Cyathus
      stercoreus.
AB  - Three new polyketide-type antioxidative compounds, cyathusals A (1), B (2), and C
      (3), and the known pulvinatal (4) were obtained from the fermented mushroom
      Cyathus stercoreus. The structures of the compounds were characterized on the
      basis of NMR and mass spectroscopic data. Cyathusals A, B, and C and pulvinatal
      showed free radical scavenging activities on the 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical with EC50 values of 41.6, 46.0, 26.6, and 28.6 microM,
      respectively, and on the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS)
      cation radical with EC50 values of 7.9, 11.1, 9.1, and 8.4 microM, respectively.

PMID- 17511504
TI  - Rhamnolipids from the rhizosphere bacterium Pseudomonas sp. GRP(3) that reduces
      damping-off disease in Chilli and tomato nurseries.
AB  - A detailed screening of bacterial isolates from the Central Himalayan region for
      plant growth promotion and antimycelial activity against Pythium and Phytophthora
      strains afforded seven isolates, of which three were particularly effective
      against the incidence of damping-off in field trials on chilli and tomato. In
      this investigation an initial spectroscopic survey of the methanolic extracts of
      the seven bacterial isolates showed complex mixtures except for Pseudomonas sp.
      GRP3, one of the most promising isolates on the basis of field studies. Strain
      GRP3 was selected for structural characterization of its secondary metabolites,
      particularly glycolipids. The extracellular secondary metabolites were enriched
      by Amberlite XAD-16 adsorber resin followed by separation and structural analysis
      using TLC, LC-MS, MS-MS, and NMR spectroscopy. Acquired data show the presence of
      a number of mono- and dirhamnolipids and include rhamnose (Rha)-C8-C10, Rha-C10
      C8, Rha-C10-C10, Rha-C10-C12:1, Rha-C10-C12, Rha-Rha-C8-C10, Rha-Rha-C10-C10, Rha
      Rha-C10-C10:1, Rha-Rha-C10-C12, Rha-Rha-C10-C12:1, Rha-Rha-C12-C12:1, and Rha-Rha
      C12-C12 in strain GRP3. Since rhamnolipids are involved in the lysis of the
      plasma membrane of zoospores of fungi, application of such rhamnolipid-producing
      rhizobacteria could facilitate control of damping-off plant pathogens.

PMID- 17511505
TI  - Resin glycosides from Ipomoea pes-caprae.
AB  - Ipomoea pes-caprae (beach morning-glory; "rinonina" for the herbal drug in
      Mexico) is prescribed by traditional healers to moderate "heat" in an infected
      kidney. The hexane-soluble extract from the aerial parts of this medicinal plant,
      through preparative-scale recycling HPLC, yielded six new lipophilic
      oligosaccharides of jalapinolic acid: pescaproside B (1) and pescapreins V-IX (2
      6). The previously known pescaproside A (7), pescapreins I-IV (8-11), and
      stoloniferin III (12) were also identified in the analyzed material by means of
      HPLC comparison with authentic samples. The glycosidic acid structure for all
      pentasaccharides was confirmed as simonic acid B. Pescaproside B (1), an acylated
      glycosidic acid methyl ester, is structurally related to pescaprein III (10).
      Pescapreins V (2) and VI (3) are diasteroisomeric tetraglycosidic lactones of
      operculinic acid C. Both of these compounds contain (2S)-methylbutyric and n
      dodecanoic acids as their esterifying residues. Pescapreins VII (4) and IX (6)
      are pentasaccharides that contain an n-decanoyl group as their esterifying fatty
      acid residue instead of the n-dodecanoyl found in pescapreins I (8) and IV (11).
      Pescaprein VIII (5) represents an isomer of pescaprein II (9) containing an n
      dodecanoyl unit as the esterifying residue at position C-4 of the third rhamnose
      moiety and a 2-methylpropanoyl at C-2 of the second rhamnose. High-field NMR
      spectroscopy and FAB mass spectrometry were used to characterize all new isolated
      compounds.

PMID- 17511506
TI  - Direct access to 1,4-dihydroxyanthraquinones: the Hauser annulation reexamined
      with p-quinones.
AB  - 3-Phenylsulfanylphthalides (e.g. 8a) readily react with p-benzoquinones in the
      presence of LiOtBu in THF to furnish 1,4-dihydroxyanthraquinones in good yields
      and one-pot operations.

PMID- 17511507
TI  - Indole diterpene synthetic studies. Total synthesis of (+)-nodulisporic acid F
      and construction of the heptacyclic cores of (+)-nodulisporic acids A and B and (
      )-nodulisporic acid D.
AB  - A first-generation strategy for construction of (+)-nodulisporic acids A (1) and
      B (2) is described. The strategy entails union of the eastern and western
      hemisphere subtargets via the indole synthesis protocol developed in our
      laboratory. Subsequent elaboration of rings E and F, however, revealed the
      considerable acid instability of the C(24) hydroxyl, thereby preventing further
      advancement. Nonetheless, preparation of the heptacyclic core of (+)-nodulisporic
      acids A and B, the total synthesis of (+)-nodulisporic acid F, the simplest
      member of the nodulisporic acid family, and elaboration of the heptacyclic core
      of (-)-nodulisporic acid D were achieved.

PMID- 17511508
TI  - Indole diterpene synthetic studies: development of a second-generation synthetic
      strategy for (+)-nodulisporic acids A and B.
AB  - A second-generation strategy for construction of (+)-nodulisporic acids A and B
      based on the development of a new, effective modular indole synthesis exploiting
      a sequential Stille cross-coupling/Buchwald-Hartwig union/cyclization tactic is
      disclosed. This strategy evolved due to the considerable acid instability of the
      C(24) hydroxyl group observed in several advanced intermediates during our first
      generation approach.

PMID- 17511509
TI  - Bis- and trisuracil nucleosides with nucleobases anchored to 11-, 12-, and 16
      membered macrocyclic scaffolds: synthesis and aggregation study.
AB  - Bis- and trisuracil nucleosides, in which the nucleobases are anchored to
      isoxazoline ring-fused 11-, 12-, and 16-membered macrooxacycles, were synthesized
      by nucleosidation of 1,2-isopropylidenefuranose ring-fused macrocycles. The
      nucleosides exhibited spherical and fiber-like morphologies in water. In one
      case, the morphology was significantly altered by complexation with an adenine
      nucleoside via complementary base pairing.

PMID- 17511510
TI  - Formation and rupture of Schottky nanocontacts on ZnO nanocolumns.
AB  - In this paper, the electrical transport and mechanical properties of Pt/ZnO
      Schottky nanocontacts have been studied simultaneously during the formation and
      rupture of the nanocontacts. By combining multidimensional conducting scanning
      force spectroscopy with appropriated data processing, the physical relevant
      parameters (the ideality factor, the Schottky barrier height, and the rupture
      voltage) are obtained. It has been found that the transport curves strongly
      depend on the loading force. For loading forces higher than a threshold value,
      the transport characteristics are similar to those of large-area Schottky
      contact, while below this threshold deviations from strictly thermionic emission
      are detected. Above the threshold, stable and reproducible Pt/ZnO nanocontacts
      with ideality factors of about 2 and Schottky barrier heights of around 0.45 eV
      have been obtained.

PMID- 17511511
TI  - A first look at ARFome: dual-coding genes in mammalian genomes.
AB  - Coding of multiple proteins by overlapping reading frames is not a feature one
      would associate with eukaryotic genes. Indeed, codependency between codons of
      overlapping protein-coding regions imposes a unique set of evolutionary
      constraints, making it a costly arrangement. Yet in cases of tightly coexpressed
      interacting proteins, dual coding may be advantageous. Here we show that although
      dual coding is nearly impossible by chance, a number of human transcripts contain
      overlapping coding regions. Using newly developed statistical techniques, we
      identified 40 candidate genes with evolutionarily conserved overlapping coding
      regions. Because our approach is conservative, we expect mammals to possess more
      dual-coding genes. Our results emphasize that the skepticism surrounding
      eukaryotic dual coding is unwarranted: rather than being artifacts, overlapping
      reading frames are often hallmarks of fascinating biology.

PMID- 17511512
TI  - Predictive modeling of signaling crosstalk during C. elegans vulval development.
AB  - Caenorhabditis elegans vulval development provides an important paradigm for
      studying the process of cell fate determination and pattern formation during
      animal development. Although many genes controlling vulval cell fate
      specification have been identified, how they orchestrate themselves to generate a
      robust and invariant pattern of cell fates is not yet completely understood.
      Here, we have developed a dynamic computational model incorporating the current
      mechanistic understanding of gene interactions during this patterning process. A
      key feature of our model is the inclusion of multiple modes of crosstalk between
      the epidermal growth factor receptor (EGFR) and LIN-12/Notch signaling pathways,
      which together determine the fates of the six vulval precursor cells (VPCs).
      Computational analysis, using the model-checking technique, provides new
      biological insights into the regulatory network governing VPC fate specification
      and predicts novel negative feedback loops. In addition, our analysis shows that
      most mutations affecting vulval development lead to stable fate patterns in spite
      of variations in synchronicity between VPCs. Computational searches for the basis
      of this robustness show that a sequential activation of the EGFR-mediated
      inductive signaling and LIN-12 / Notch-mediated lateral signaling pathways is key
      to achieve a stable cell fate pattern. We demonstrate experimentally a time-delay
      between the activation of the inductive and lateral signaling pathways in wild
      type animals and the loss of sequential signaling in mutants showing unstable
      fate patterns; thus, validating two key predictions provided by our modeling
      work. The insights gained by our modeling study further substantiate the
      usefulness of executing and analyzing mechanistic models to investigate complex
      biological behaviors.

PMID- 17511513
TI  - The human genomic melting map.
AB  - In a living cell, the antiparallel double-stranded helix of DNA is a dynamically
      changing structure. The structure relates to interactions between and within the
      DNA strands, and the array of other macromolecules that constitutes functional
      chromatin. It is only through its changing conformations that DNA can organize
      and structure a large number of cellular functions. In particular, DNA must
      locally uncoil, or melt, and become single-stranded for DNA replication, repair,
      recombination, and transcription to occur. It has previously been shown that this
      melting occurs cooperatively, whereby several base pairs act in concert to
      generate melting bubbles, and in this way constitute a domain that behaves as a
      unit with respect to local DNA single-strandedness. We have applied a melting map
      calculation to the complete human genome, which provides information about the
      propensities of forming local bubbles determined from the whole sequence, and
      present a first report on its basic features, the extent of cooperativity, and
      correlations to various physical and biological features of the human genome.
      Globally, the melting map covaries very strongly with GC content. Most
      importantly, however, cooperativity of DNA denaturation causes this correlation
      to be weaker at resolutions fewer than 500 bps. This is also the resolution level
      at which most structural and biological processes occur, signifying the
      importance of the informational content inherent in the genomic melting map. The
      human DNA melting map may be further explored at http://meltmap.uio.no.

PMID- 17511514
TI  - Comprehensive DNA signature discovery and validation.
AB  - DNA signatures are nucleotide sequences that can be used to detect the presence
      of an organism and to distinguish that organism from all other species. Here we
      describe Insignia, a new, comprehensive system for the rapid identification of
      signatures in the genomes of bacteria and viruses. With the availability of
      hundreds of complete bacterial and viral genome sequences, it is now possible to
      use computational methods to identify signature sequences in all of these
      species, and to use these signatures as the basis for diagnostic assays to detect
      and genotype microbes in both environmental and clinical samples. The success of
      such assays critically depends on the methods used to identify signatures that
      properly differentiate between the target genomes and the sample background. We
      have used Insignia to compute accurate signatures for most bacterial genomes and
      made them available through our Web site. A sample of these signatures has been
      successfully tested on a set of 46 Vibrio cholerae strains, and the results
      indicate that the signatures are highly sensitive for detection as well as
      specific for discrimination between these strains and their near relatives. Our
      approach, whereby the entire genomic complement of organisms are compared to
      identify probe targets, is a promising method for diagnostic assay development,
      and it provides assay designers with the flexibility to choose probes from the
      most relevant genes or genomic regions. The Insignia system is freely accessible
      via a Web interface and has been released as open source software at:
      http://insignia.cbcb.umd.edu.

PMID- 17511515
TI  - Structure of GrlR and the implication of its EDED motif in mediating the
      regulation of type III secretion system in EHEC.
AB  - Enterohemorrhagic Escherichia coli (EHEC) is a common cause of severe hemorrhagic
      colitis. EHEC's virulence is dependent upon a type III secretion system (TTSS)
      encoded by 41 genes. These genes are organized in several operons clustered in
      the locus of enterocyte effacement. Most of the locus of enterocyte effacement
      genes, including grlA and grlR, are positively regulated by Ler, and Ler
      expression is positively and negatively modulated by GrlA and GrlR, respectively.
      However, the molecular basis for the GrlA and GrlR activity is still elusive. We
      have determined the crystal structure of GrlR at 1.9 A resolution. It consists of
      a typical beta-barrel fold with eight beta-strands containing an internal
      hydrophobic cavity and a plug-like loop on one side of the barrel. Strong
      hydrophobic interactions between the two beta-barrels maintain the dimeric
      architecture of GrlR. Furthermore, a unique surface-exposed EDED (Glu-Asp-Glu
      Asp) motif is identified to be critical for GrlA-GrlR interaction and for the
      repressive activity of GrlR. This study contributes a novel molecular insight
      into the mechanism of GrlR function.

PMID- 17511516
TI  - The importance of human FcgammaRI in mediating protection to malaria.
AB  - The success of passive immunization suggests that antibody-based therapies will
      be effective at controlling malaria. We describe the development of fully human
      antibodies specific for Plasmodium falciparum by antibody repertoire cloning from
      phage display libraries generated from immune Gambian adults. Although these
      novel reagents bind with strong affinity to malaria parasites, it remains unclear
      if in vitro assays are predictive of functional immunity in humans, due to the
      lack of suitable animal models permissive for P. falciparum. A potentially useful
      solution described herein allows the antimalarial efficacy of human antibodies to
      be determined using rodent malaria parasites transgenic for P. falciparum
      antigens in mice also transgenic for human Fc-receptors. These human IgG1s cured
      animals of an otherwise lethal malaria infection, and protection was crucially
      dependent on human FcgammaRI. This important finding documents the capacity of
      FcgammaRI to mediate potent antimalaria immunity and supports the development of
      FcgammaRI-directed therapy for human malaria.

PMID- 17511518
TI  - Out of Africa: a molecular perspective on the introduction of yellow fever virus
      into the Americas.
AB  - Yellow fever virus (YFV) remains the cause of severe morbidity and mortality in
      South America and Africa. To determine the evolutionary history of this important
      reemerging pathogen, we performed a phylogenetic analysis of the largest YFV data
      set compiled to date, representing the prM/E gene region from 133 viral isolates
      sampled from 22 countries over a period of 76 years. We estimate that the
      currently circulating strains of YFV arose in Africa within the last 1,500 years
      and emerged in the Americas following the slave trade approximately 300-400 years
      ago. These viruses then spread westwards across the continent and persist there
      to this day in the jungles of South America. We therefore illustrate how gene
      sequence data can be used to test hypotheses of viral dispersal and demographics,
      and document the role of human migration in the spread of infectious disease.

PMID- 17511517
TI  - Crystal structure of the P pilus rod subunit PapA.
AB  - P pili are important adhesive fibres involved in kidney infection by
      uropathogenic Escherichia coli strains. P pili are assembled by the conserved
      chaperone-usher pathway, which involves the PapD chaperone and the PapC usher.
      During pilus assembly, subunits are incorporated into the growing fiber via the
      donor-strand exchange (DSE) mechanism, whereby the chaperone's G1 beta-strand
      that complements the incomplete immunoglobulin-fold of each subunit is displaced
      by the N-terminal extension (Nte) of an incoming subunit. P pili comprise a
      helical rod, a tip fibrillum, and an adhesin at the distal end. PapA is the rod
      subunit and is assembled into a superhelical right-handed structure. Here, we
      have solved the structure of a ternary complex of PapD bound to PapA through
      donor-strand complementation, itself bound to another PapA subunit through DSE.
      This structure provides insight into the structural basis of the DSE reaction
      involving this important pilus subunit. Using gel filtration chromatography and
      electron microscopy on a number of PapA Nte mutants, we establish that PapA
      differs in its mode of assembly compared with other Pap subunits, involving a
      much larger Nte that encompasses not only the DSE region of the Nte but also the
      region N-terminal to it.

PMID- 17511519
TI  - A method to address differential bias in genotyping in large-scale association
      studies.
AB  - In a previous paper we have shown that, when DNA samples for cases and controls
      are prepared in different laboratories prior to high-throughput genotyping,
      scoring inaccuracies can lead to differential misclassification and,
      consequently, to increased false-positive rates. Different DNA sourcing is often
      unavoidable in large-scale disease association studies of multiple case and
      control sets. Here, we describe methodological improvements to minimise such
      biases. These fall into two categories: improvements to the basic clustering
      methods for identifying genotypes from fluorescence intensities, and use of
      "fuzzy" calls in association tests in order to make appropriate allowance for
      call uncertainty. We find that the main improvement is a modification of the
      calling algorithm that links the clustering of cases and controls while allowing
      for different DNA sourcing. We also find that, in the presence of different DNA
      sourcing, biases associated with missing data can increase the false-positive
      rate. Therefore, we propose the use of "fuzzy" calls to deal with uncertain
      genotypes that would otherwise be labeled as missing.

PMID- 17511520
TI  - Being pathogenic, plastic, and sexual while living with a nearly minimal
      bacterial genome.
AB  - Mycoplasmas are commonly described as the simplest self-replicating organisms,
      whose evolution was mainly characterized by genome downsizing with a proposed
      evolutionary scenario similar to that of obligate intracellular bacteria such as
      insect endosymbionts. Thus far, analysis of mycoplasma genomes indicates a low
      level of horizontal gene transfer (HGT) implying that DNA acquisition is strongly
      limited in these minimal bacteria. In this study, the genome of the ruminant
      pathogen Mycoplasma agalactiae was sequenced. Comparative genomic data and
      phylogenetic tree reconstruction revealed that approximately 18% of its small
      genome (877,438 bp) has undergone HGT with the phylogenetically distinct mycoides
      cluster, which is composed of significant ruminant pathogens. HGT involves genes
      often found as clusters, several of which encode lipoproteins that usually play
      an important role in mycoplasma-host interaction. A decayed form of a conjugative
      element also described in a member of the mycoides cluster was found in the M.
      agalactiae genome, suggesting that HGT may have occurred by mobilizing a related
      genetic element. The possibility of HGT events among other mycoplasmas was
      evaluated with the available sequenced genomes. Our data indicate marginal levels
      of HGT among Mycoplasma species except for those described above and, to a lesser
      extent, for those observed in between the two bird pathogens, M. gallisepticum
      and M. synoviae. This first description of large-scale HGT among mycoplasmas
      sharing the same ecological niche challenges the generally accepted evolutionary
      scenario in which gene loss is the main driving force of mycoplasma evolution.
      The latter clearly differs from that of other bacteria with small genomes,
      particularly obligate intracellular bacteria that are isolated within host cells.
      Consequently, mycoplasmas are not only able to subvert complex hosts but
      presumably have retained sexual competence, a trait that may prevent them from
      genome stasis and contribute to adaptation to new hosts.

PMID- 17511521
TI  - Genetic and physical mapping of DNA replication origins in Haloferax volcanii.
AB  - The halophilic archaeon Haloferax volcanii has a multireplicon genome, consisting
      of a main chromosome, three secondary chromosomes, and a plasmid. Genes for the
      initiator protein Cdc6/Orc1, which are commonly located adjacent to archaeal
      origins of DNA replication, are found on all replicons except plasmid pHV2.
      However, prediction of DNA replication origins in H. volcanii is complicated by
      the fact that this species has no less than 14 cdc6/orc1 genes. We have used a
      combination of genetic, biochemical, and bioinformatic approaches to map DNA
      replication origins in H. volcanii. Five autonomously replicating sequences were
      found adjacent to cdc6/orc1 genes and replication initiation point mapping was
      used to confirm that these sequences function as bidirectional DNA replication
      origins in vivo. Pulsed field gel analyses revealed that cdc6/orc1-associated
      replication origins are distributed not only on the main chromosome (2.9 Mb) but
      also on pHV1 (86 kb), pHV3 (442 kb), and pHV4 (690 kb) replicons. Gene
      inactivation studies indicate that linkage of the initiator gene to the origin is
      not required for replication initiation, and genetic tests with autonomously
      replicating plasmids suggest that the origin located on pHV1 and pHV4 may be
      dominant to the principal chromosomal origin. The replication origins we have
      identified appear to show a functional hierarchy or differential usage, which
      might reflect the different replication requirements of their respective
      chromosomes. We propose that duplication of H. volcanii replication origins was a
      prerequisite for the multireplicon structure of this genome, and that this might
      provide a means for chromosome-specific replication control under certain growth
      conditions. Our observations also suggest that H. volcanii is an ideal organism
      for studying how replication of four replicons is regulated in the context of the
      archaeal cell cycle.

PMID- 17511522
TI  - Allele-specific chromatin immunoprecipitation studies show genetic influence on
      chromatin state in human genome.
AB  - Several recent studies have shown a genetic influence on gene expression
      variation, including variation between the two chromosomes within an individual
      and variation between individuals at the population level. We hypothesized that
      genetic inheritance may also affect variation in chromatin states. To test this
      hypothesis, we analyzed chromatin states in 12 lymphoblastoid cells derived from
      two Centre d'Etude du Polymorphisme Humain families using an allele-specific
      chromatin immunoprecipitation (ChIP-on-chip) assay with Affymetrix 10K SNP chip.
      We performed the allele-specific ChIP-on-chip assays for the 12 lymphoblastoid
      cells using antibodies targeting at RNA polymerase II and five post-translation
      modified forms of the histone H3 protein. The use of multiple cell lines from the
      Centre d'Etude du Polymorphisme Humain families allowed us to evaluate variation
      of chromatin states across pedigrees. These studies demonstrated that chromatin
      state clustered by family. Our results support the idea that genetic inheritance
      can determine the epigenetic state of the chromatin as shown previously in model
      organisms. To our knowledge, this is the first demonstration in humans that
      genetics may be an important factor that influences global chromatin state
      mediated by histone modification, the hallmark of the epigenetic phenomena.

PMID- 17511523
TI  - Male involvement in reproductive health among scheduled tribe: experience from
      Khairwars of central India.
AB  - INTRODUCTION: Indian tribal men's lack of participation in reproductive health
      not only damages their own health, but also contributes to the reproductive ill
      health of their female partners and children. In India the involvement of men in
      such matters is a new concept. There is a paucity of data particularly on
      Scheduled tribesmen's knowledge and the extent of their participation in
      reproductive health. This inhibits planning. The present study aims to understand
      the involvement of Scheduled tribesmen in reproductive health and the barriers to
      their involvement by generating a database from the Khairwar tribe of Central
      India. METHODS: A door-to-door survey on knowledge, attitude and practice
      relating to aspects of reproductive health was conducted by canvassing a pre
      designed interview schedule among 15-40 year old, currently married Khairwar
      males in the Sidhi district of Madhya Pradesh, India. RESULTS: As far as
      reproductive morbidity is concerned, only 17% of the respondents had heard of
      HIV/AIDS, and most had no proper knowledge of its transmission. Although 74% of
      the respondents had heard about reproductive tract infections, the majority of
      them were unaware of the mechanism of transmission and seriousness of the
      problem. The duel role of condoms, both as a method of family planning and a
      protective measure against sexually transmitted infections, was also unknown to
      them. Approximately 59% of the males were aware of family planning but only 13%
      were using any method (mostly female sterilization) at the time of survey. Their
      view on the ideal number of children (3.56) exceeded the actual number of
      children born and living. High infant and child mortality influenced their
      preference for higher fertility. Very few among them (29%) had knowledge of
      antenatal care. They expressed faulty knowledge, myths and unhelpful attitudes
      towards sexual health matters. CONCLUSION: The study revealed the male Scheduled
      tribe population's lack of knowledge and misinformation regarding male sexual
      health issues, the gender inequality in Indian society, and a lack of male
      oriented reproductive health services, all of which deter men from sharing the
      responsibility.

PMID- 17511524
TI  - Diagnostic delay among pulmonary tuberculosis patients in Sarawak, Malaysia: a
      cross-sectional study.
AB  - INTRODUCTION: Delayed diagnosis of tuberculosis (TB) can lead to an increased
      period of infectivity in the community, a delay in treatment and a severe form of
      the disease. The objective of this study was to determine the length of delay,
      and factors linking the delay from the onset of symptoms of pulmonary
      tuberculosis (PTB) until the commencement of treatment in Sarawak, Malaysia.
      METHODS: An institution based cross-sectional study was conducted in 10 TB
      clinics in randomly selected divisions in Sarawak from June 2003 to May 2004.
      Delay was analyzed from two perspectives: (1) period between the onset of TB
      symptoms to any first medical consultation (patients' delay); and (2) period
      between the first medical consultation to the diagnosis of TB (diagnosis delay).
      Patients were interviewed on diagnosis or within the admission period using a
      semi-structured questionnaire. RESULTS: A total of 316 new smear-positive PTB
      patients participated in the study. The median patient interval was 30 days.
      Gender was found to be significantly associated with patient delay. The median
      diagnosis interval was 22 days. Respondents' incomes, health-care professional
      first consulted and actions taken by the health-care providers during the first
      consultation were significantly associated with diagnosis delay. The medium
      treatment interval was 0 days. CONCLUSION: Both patients and health providers
      played a role in delaying TB diagnosis. Females appeared to have longer delay.
      Respondents living above the poverty line had diagnosis delay as they made more
      visits to GPs or different government clinics without proper investigations for
      TB. A mechanism is needed to increase all health-care providers' suspicion of TB
      so that proper investigations can be done during first consultation.

PMID- 17511529
TI  - Workstyle and overcommitment in relation to neck and upper limb symptoms.
AB  - Few studies have examined the concepts of workstyle and overcommitment in
      relation to the occurrence of neck and upper limb symptoms. The aim of this study
      was to examine whether a high-risk workstyle is a mediator in the relation of
      work-related exposure (job demands and computer work) and overcommitment to neck
      and upper limb symptoms. The study participants comprised 3,855 office workers of
      a European institute. The Sobel test was applied to test the intermediate effects
      of 4 workstyle dimensions and of the total workstyle score. The results show that
      most mediated effects were statistically significant, meaning that the workstyle
      dimensions acted as a mediator in the relation between work-related exposure and
      symptoms as well as in the relation between overcommitment and symptoms. Given
      the results with the total workstyle score, 34% of the effect of prolonged
      computer work, 64% of the effect of job demands, and 84% of the effect of
      overcommitment was mediated by workstyle. However, due to possible bias in the
      assessment of workstyle factor and the cross-sectional design of the study, the
      conclusions should be drawn with care.

PMID- 17511528
TI  - The impact of the financial costs of multiple sclerosis on quality of life.
AB  - This study examined the financial costs of multiple sclerosis (MS) and the impact
      of financial strain on the subjective quality of life of people with MS and their
      families. Due to the lack of research in this area, a qualitative research design
      was employed. Interviews were conducted with 16 health professionals, 26 people
      with MS, and 11 family members of people who had MS. Adjusting to actual or
      threatened loss of income caused financial stress. These financial struggles led
      to a lower quality of life among respondents. Problem solving, coping, and
      positive reappraisal helped people to adjust to financial changes. Professionals
      focused on increased funding for services, whereas people with MS focused on
      improved income support. These findings highlight the need for professionals to
      consider the financial strain associated with this disease and the impact of this
      strain on the quality of life of individuals with MS and their families.

PMID- 17511530
TI  - Psychosocial factors at home and at work and four-year progression in intima
      media thickness.
AB  - This study analyzed the relationship between psychosocial factors and progression
      in intima media thickness (IMT). In 1998 and 2002, 95 healthy participants
      underwent a clinical examination, including ultrasound of the arteria carotis
      communis (ACC). IMT progression in women was 0.033 mm/year (SD=0.033) and in men
      0.048 mm/year (SD=0.033). For cohabiting women as opposed to single women, the
      means for total IMT progression over the 4 years were, respectively, 0.137
      (SE=0.019) and 0.016 (SE=0.048) mm. For women with above average as opposed to
      below average mean scores of effort, IMT progression were 0.149 (SE=0.026) and
      0.098 (SE=0.024) mm, respectively. For men without children as opposed to men
      with children, mean scores for IMT progression were 0.231 (SE=0.029) and 0.137
      (SE=0.028) mm, respectively. For men above average as opposed to those below
      average, scores of effort-reward imbalance IMT progression were 0.216 (SE=0.030)
      and 0.155 (SE=0.027) mm, respectively. Adjustment for confounders did not change
      the results significantly. We found that psychosocial factors were independent
      significant predictors of IMT progression. The associations were different
      between the genders.

PMID- 17511532
TI  - Do stressors explain the association between income and declines in self-rated
      health? A longitudinal analysis of the National Population Health Survey.
AB  - Although there is considerable evidence documenting the relationship between
      lower socioeconomic status (SES) and poorer health, longitudinal research is
      needed to study mechanisms that may explain this relationship. This study
      investigated whether income was associated with decline in self-rated health over
      a 2-year period and whether stressors mediated part of this social gradient.
      Participants in the National Population Health Survey (NPHS) who rated their
      health as excellent, very good, or good in 1994 and 1995 were followed over 2
      years. Analyses demonstrated that individuals in the 2 lowest household income
      quintiles had significantly greater odds of experiencing a decline in health
      status as compared to the highest quintile. Seven of 8 reported stressors at
      baseline were each associated with a significantly increased odds of experiencing
      a decline in self-rated health. Furthermore, these stressors explained 16% and
      10% of the relationship between the lowest and 2nd lowest income quintiles and
      decline in self-rated health, respectively. These results suggest that stressors
      may be 1 mechanism underlying the social gradient in health.

PMID- 17511531
TI  - Planning and strategy use in health behavior change: a life span view.
AB  - Exercise-related strategy use and planning were investigated in younger (18-49
      years) and older individuals (50-80 years) in orthopedic rehabilitation who were
      supposed to adhere to a strict exercise regimen. As part of a longitudinal study,
      N=368 individuals completed questionnaires assessing the amount of physical
      activities performed pre-rehabilitation and 6 and 12 months after discharge. In
      addition, the extent of strategy use (selection, optimization, and compensation)
      and planning after discharge was assessed. Planning was subdivided into two
      constructs: action planning (planning when, where, and how to exercise) and
      coping planning (planning how to exercise in the face of barriers). Two-sample
      structural equation modeling was used. For both age groups, strategy use improved
      prediction of exercise goal attainment on top of planning, while strategy use
      mediated the relationship between coping planning and goal attainment.
      Interventions fostering strategy use as well as planning might enhance exercise
      adherence across age groups.

PMID- 17511533
TI  - A randomized controlled trial of two weight-reducing short-term group treatment
      programs for obesity with an 18-month follow-up.
AB  - We found in an earlier study that participants in a short-term treatment program
      for obesity showed a good weight reduction (10.4 kg) 18 months after treatment
      terminated. The program included elements from cognitive therapy (CT) and
      psychoeducation. In the present study the efficacy of a slight modification of
      the same treatment program (cognitive treatment group) was compared with a
      behavioral program that included moderate-intensity physical activity and
      behavioral techniques (the control treatment group) in a randomized controlled
      trial. The primary effect variable was weight change 18 months after the end of
      therapy. Both treatment programs lasted for 10 weeks (2 hr/week), and thereafter
      the participants were weighed periodically over an 18-month period. The
      participants were obese women employed outside the home. Twelve of the
      participants did not receive treatment after randomization. Eleven of these
      participants had been randomized to the cognitive program, whereas the remaining
      participant was randomized to the control program. The mean age for those that
      began the 2 programs was 48.5 years, and the mean body mass index (BMI) was 36.6.
      For those who completed the treatment programs and participated in the 18-month
      follow-up, the baseline BMI was 34.7. One participant in the cognitive treatment
      group (n=16) and 6 in the control program (n=26) dropped out during treatment.
      Both per-protocol and intention-to-treat analyses were performed on the data.
      Fifteen participants (94%) completed the cognitive program. Of these, 13 (87%)
      participated at the 18-month follow-up. Their mean weight loss at treatment
      completion was 8.6 kg(SD=2.9) and 18 months later 5.9 kg (SD=5.4). Twenty
      participants (77%) completed the control program. Of these, 16 (80%) participated
      in the 18-month follow-up. Their mean weight loss at the end of treatment was 0.7
      kg (SD=1.2), and 18 months later they showed an increase in weight of 0.3 kg
      (SD=4.3) as compared with baseline weight. The weight differences between the 2
      program groups were highly significant (p<.01-.001) at all posttreatment
      weighings. In the intention-to-treat analysis, all participants who started the
      cognitive treatment (n=16) or control program (n=26) were included. The last
      observation carried forward was used for those who dropped out from therapy or
      from follow-up. Eighteen months after the end of therapy, the mean weight loss
      was 5.5 kg (SD=5.5) in the cognitive group, whereas the control group evidenced a
      weight loss of 0.6 kg (SD=5.5). The weight change differences between the 2
      groups were highly significant at all follow-up weighings (p<.001). The low drop
      out rate during the treatment period demonstrates that the participants found the
      2 programs acceptable. The long-term efficacy of the cognitive treatment program
      seems to be satisfactory. With its group format and short treatment duration, the
      cognitive program is attractive from a cost-effective standpoint.

PMID- 17511534
TI  - Guidelines for the management of severe traumatic brain injury.

PMID- 17511535
TI  - Guidelines for the management of severe traumatic brain injury. Introduction.

PMID- 17511539
TI  - Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar
      therapy.

PMID- 17511540
TI  - Guidelines for the management of severe traumatic brain injury. III. Prophylactic
      hypothermia.

PMID- 17511541
TI  - Guidelines for the management of severe traumatic brain injury. IV. Infection
      prophylaxis.

PMID- 17511542
TI  - Guidelines for the management of severe traumatic brain injury. Methods.

PMID- 17511543
TI  - Guidelines for the management of severe traumatic brain injury. V. Deep vein
      thrombosis prophylaxis.

PMID- 17511544
TI  - Guidelines for the management of severe traumatic brain injury. VI. Indications
      for intracranial pressure monitoring.

PMID- 17511545
TI  - Guidelines for the management of severe traumatic brain injury. VII. Intracranial
      pressure monitoring technology.

PMID- 17511546
TI  - Guidelines for the management of severe traumatic brain injury. VIII.
      Intracranial pressure thresholds.

PMID- 17511547
TI  - Guidelines for the management of severe traumatic brain injury. IX. Cerebral
      perfusion thresholds.

PMID- 17511548
TI  - Guidelines for the management of severe traumatic brain injury. X. Brain oxygen
      monitoring and thresholds.

PMID- 17511549
TI  - Guidelines for the management of severe traumatic brain injury. I. Blood pressure
      and oxygenation.

PMID- 17511550
TI  - Guidelines for the management of severe traumatic brain injury. XI. Anesthetics,
      analgesics, and sedatives.

PMID- 17511551
TI  - Guidelines for the management of severe traumatic brain injury. XII. Nutrition.

PMID- 17511552
TI  - Guidelines for the management of severe traumatic brain injury. XIII. Antiseizure
      prophylaxis.

PMID- 17511553
TI  - Guidelines for the management of severe traumatic brain injury. XIV.
      Hyperventilation.

PMID- 17511554
TI  - Guidelines for the management of severe traumatic brain injury. XV. Steroids.

PMID- 17511557
TI  - Guidelines for the management of severe traumatic brain injury. Editor's
      Commentary.

PMID- 17511558
TI  - Translational regenerative medicine research: essential to discovery and outcome.

PMID- 17511561
TI  - Stem cells and plasticity of skeletal muscle cell differentiation: potential
      application to cell therapy for degenerative muscular diseases.
AB  - Degenerative muscular diseases, such as muscular dystrophies, have been the
      representative targets of regenerative cell therapy. Although satellite cells
      play central roles in skeletal muscle regeneration that intrinsically occurs
      after muscle injury, their application to cell therapy is confronted by
      difficulties. Other stem cells expected to be applicable to cell therapy include
      muscle-resident stem cells and nonmuscle-resident stem cells. Moreover,
      dedifferentiated cells of skeletal muscle might provide unique system for cell
      therapy. Terminally differentiated myotubes have plasticity of differentiation
      and dedifferentiate under certain experimental conditions, including the
      expression of SV40 large T antigen or the homeobox gene Msx1. The
      dedifferentiated cells exhibit multipotency to transdifferentiate into multiple
      mesenchymal origin cells. In addition, fibroblasts or undifferentiated myoblasts
      treated with a drug acquire multipotency. These cells may open new doors in cell
      therapy.

PMID- 17511562
TI  - Cellular therapy in Chagas' disease: potential applications in patients with
      chronic cardiomyopathy.
AB  - Nearly a century after its discovery, Chagas' disease, caused by the protozoan
      Trypanosoma cruzi, remains a major health problem in Latin America. Although
      efforts in transmission control have contributed to a decrease in the number of
      new cases, approximately a third of chronic Chagasic individuals have or will
      develop the symptomatic forms of the disease, mainly cardiomyopathy. Chagas'
      disease is a progressively debilitating disease, which, at the final stages,
      there are no currently available treatments other than heart transplantation. In
      this scenario, cellular therapy is being tested as an alternative for millions of
      patients with heart dysfunction due to Chagas' disease. In this article, we
      review the studies of cellular therapy in animal models and in patients with
      Chagasic cardiomyopathy and the possible mechanisms by which cellular therapy may
      act in this disease.

PMID- 17511563
TI  - Challenges and approaches to the culture of pluripotent human embryonic stem
      cells.
AB  - Since the establishment of the first human embryonic stem cell (hESC) lines,
      several groups have described the derivation and culture of hESC lines in various
      culture conditions. In this review, we describe how hESC lines have been derived
      from the inner cell mass of blastocysts or morula-stage embryos and the culture
      conditions used. In order to be used for therapeutic purposes, the pluripotent
      hESC lines must be established and propagated according to good manufacturing
      practice quality requirements. In addition, any use of animal-derived components
      should be avoided to gain safer hESC lines for clinical purposes. Here, we will
      describe the development in derivation and chemically defined culturing
      conditions of hESC towards good manufacturing practice and discuss the future
      challenges for hESCs in clinical use. Similarly, we discuss the challenges and
      future directions in optimization of standard culture conditions of hESCs for
      research purposes.

PMID- 17511564
TI  - Multipotential mesoangioblast stem cell therapy in the mdx/utrn-/- mouse model
      for Duchenne muscular dystrophy.
AB  - BACKGROUND: Duchenne muscular dystrophy is a progressive, lethal muscle-wasting
      disease for which there is no treatment. MATERIALS & METHODS: We have isolated
      wild-type mesoangioblasts from aorta and tested their effectiveness in
      alleviating severe muscle disease in the dystrophin/utrophin knockout (mdx/utrn-/
      ) mouse model for Duchenne muscular dystrophy. RESULTS: Mesoangioblast clones
      express Sca-1 and Flk-1 and differentiate into smooth and skeletal muscle, glial
      cells and adipocytes in vitro. Mesoangioblasts proliferate in vivo, incorporate
      into muscle fibers, form new fibers, and promote synthesis of dystrophin and
      utrophin. Muscle fibers that have incorporated mesoangioblasts, as well as
      surrounding fibers, are protected from damage, with approximately 50-fold less
      damage than fibers in muscle injected with saline. Some mesoangioblasts localize
      beneath the basal lamina and express c-met, whereas others differentiate into
      smooth muscle cells at the periphery of vessels and express alpha-smooth muscle
      actin. In mdx/utrn-/- muscle, some mesoangioblasts also form Schwann cells.
      DISCUSSION & CONCLUSION: Mesoangioblasts differentiate into multiple cell types
      damaged during the progression of severe muscle disease and protect fibers from
      damage. As such, they are good candidates for therapy of Duchenne muscular
      dystrophy and perhaps other neuromuscular diseases.

PMID- 17511565
TI  - Transplantation of 3D scaffolds seeded with human embryonic stem cells:
      biological features of surrogate tissue and teratoma-forming potential.
AB  - AIM: To generate complex surrogate tissue by transplanting 3D scaffolds seeded
      with human embryonic stem cells (hESCs) between the liver lobules of severe
      combined immunodeficient (SCID) mice and to assess the teratoma-forming
      potential. MATERIALS & METHODS: 3D poly-(lactic-co-glycolic acid) (PLGA)
      scaffolds coated with laminin were seeded with hESCs and then transplanted
      between the liver lobules of SCID mice. After a period of in vivo
      differentiation, the scaffolds were retrieved and analyzed using reverse
      transcription polymerase chain reaction, immunofluorescent staining and scanning
      electron microscopy. RESULTS: A proportion of the hESCs within the scaffolds
      differentiated into cells that produced proteins characteristic of specific
      tissues, including endoderm and pancreatic markers glucogon-like peptide-1
      receptor, islet amyloid polypeptide and Insulin. Markers of hepatic and neuronal
      lineages were also investigated. Major matrix proteins abundant in multiple
      tissue types, including collagen I, laminin and collagen IV, were found to be
      profuse within the scaffold pores. Transplantation of the seeded scaffolds
      between liver lobules also resulted in extensive vascularization both from host
      blood vessel incursion and the differentiation of hESCs into endothelial
      progenitor cells. An investigation of teratoma-forming potential demonstrated
      that transplantation of 3D scaffolds seeded with hESCs will, under certain
      conditions, lead to the growth of teratomas. DISCUSSION: Transplantation of 3D
      scaffolds seeded with hESCs between liver lobules resulted in the development of
      surrogate tissue containing cells that produced proteins representing the
      pancreatic, hepatic and neuronal lineages, the assembly of an extracellular
      matrix structure and the formation of a vasculature. hESCs seeded within 3D
      scaffolds and transplanted into SCID mice were capable of forming teratomas.
      However, the formation and progression of teratoma growth is shown to be
      dependant on both the site of transplantation and the treatment of cells prior to
      transplantation.

PMID- 17511566
TI  - Patenting, morality and human embryonic stem cell science: bioethics and cultural
      politics in Europe.
AB  - As the recent experience of the European Patent Office graphically demonstrates,
      there is an inherent political tension between the individual ownership rights
      necessary for the operation of an international market in human embryonic stem
      cell science and the communal values of the many cultures in which such markets
      operate. This report examines the basis of the conflict between patenting and
      morality at national and international levels, the manifestation of those
      tensions in European patenting policy, and the contribution of bioethics to the
      attempt by European institutions to develop a governance response.

PMID- 17511567
TI  - Stem cells: moving the biology towards the clinic.

PMID- 17511568
TI  - Cytori Therapeutics, Inc.
AB  - Cytori Therapeutics, Inc. develops stem and regenerative cell therapies that can
      be used in a 'real-time' treatment setting for cardiovascular disease,
      reconstructive surgery and many other serious, chronic and life-threatening
      conditions and disorders. Cytori uses adult stem cells from adipose tissue, which
      offers a rich, accessible and autologous source of adult stem cells, and
      maximizes these benefits to create a cost-effective and safe treatment option.

PMID- 17511569
TI  - Socio-demographic and economic correlates of overweight status in Chinese
      adolescents.
AB  - OBJECTIVE: To investigate over-weight prevalence and socio-demographic and
      economic correlates in Chinese adolescents. METHODS: Weight, height, waist
      circumference, and socio-demo-graphic and economic variables of 6863 middle and
      high school students were measured. RESULTS: 10% of girls and 17% of boys were
      overweight. Waist circumference and overweight risk were significantly associated
      with pubertal status (P<0.05). High levels of parental education and family
      income were significant risk factors for overweight (P<0.05). DISCUSSION: Our
      findings underscore the need for development of evidence-based and culturally
      appropriate public health programs to prevent and treat pediatric obesity in
      China.

PMID- 17511570
TI  - Social influences on cigarette initiation among college students.
AB  - OBJECTIVES: To examine the relationship of demographic and social influence with
      initiation of cigarette use among undergraduates. METHODS: Students were mailed
      anonymous surveys including 437 participants who indicated that they had not
      smoked cigarettes before age 18. Of those, 107 became late initiators (24%), and
      330 remained never smokers (76%). RESULTS: Those who drank alcohol in college and
      had at least 1 parent with a college education were more likely to initiate
      smoking than were those who did not drink and neither parent had attended
      college. CONCLUSIONS: Strategies that focus on reducing alcohol and tobacco use
      need to be tested.

PMID- 17511571
TI  - Disparities in overweight and obesity among US college students.
AB  - OBJECTIVES: To examine social disparities and behavioral correlates of overweight
      and obesity over time among college students. METHODS: Multilevel analyses of
      BMI, physical activity, and television viewing from 2 representative surveys of
      US college students (n=24,613). RESULTS: Overweight and obesity increased over
      time and were higher among males, African Americans, and students of lower
      socioeconomic position and lower among Asians. Television viewing and in activity
      were associated with obesity, and disparities in these behaviors partially
      accounted for excess weight among African Americans. CONCLUSIONS: Social
      disparities in overweight and obesity exist among college students. Promoting
      physical activity and reducing television viewing may counteract increasing
      trends.

PMID- 17511572
TI  - Built environment and psychosocial factors associated with trail proximity and
      use.
AB  - OBJECTIVES: To explore the relationships among neighborhood built environment
      characteristics, psychosocial factors, perceived and objective proximity
      assessments, and use of a community rail-trail. METHOD: Telephone survey data of
      adults (n=788) in Morgantown, WVa, were classified into one of 4 distance
      perception categories based on actual (using geographic information systems
      technology) and perceived proximity of a community rail-trail. RESULTS:
      Differences in psychosocial barriers to physical activity (P=.037) and perceived
      neighborhood walkability (P<.001) were associated with perceived proximity to and
      use of a community trail. CONCLUSION: Specific attention should be given to
      address neighborhood and psychosocial barriers when constructing and promoting
      community trails.

PMID- 17511573
TI  - Road rage and collision involvement.
AB  - OBJECTIVES: To assess the contribution of road rage victimization and
      perpetration to collision involvement. METHODS: The relationship between self
      reported collision involvement and road rage victimization and perpetration was
      examined, based on telephone interviews with a representative sample of 4897
      Ontario adult drivers interviewed between 2002 and 2004. RESULTS: Perpetrators
      and victims of both any road rage and serious road rage had a significantly
      higher risk of collision involvement than did those without road rage experience.
      CONCLUSIONS: This study provides epidemiological evidence that both victims and
      perpetrators of road rage experience increased collision risk. More detailed
      studies of the contribution of road rage to traffic crashes are needed.

PMID- 17511574
TI  - Utilization of mental health services and risk of 12-month problematic alcohol
      use.
AB  - OBJECTIVE: To examine whether mental health service utilization modifies the
      association between lifetime anxiety or depressive disorders (ADD) and risk of 12
      month problematic alcohol use. METHODS: Randomly selected members (n=6518) of a
      mutual health-insurance company were evaluated for lifetime ADD (DSM-IV), mental
      health service utilization for ADD, and risk of 12-month problematic alcohol use
      (DSM-IV and CAGE). RESULTS: Risk of 12-month problematic alcohol use was reduced
      when mental health services had been used for several ADD (OR=3.3 vs 5.8), but
      not for one ADD. CONCLUSIONS: These results show the importance of taking mental
      health service use into account as a potential effect-modifier of psychiatric
      comorbidity.

PMID- 17511575
TI  - College students' expectancies for light cigarettes and potential reduced
      exposure products.
AB  - OBJECTIVES: To determine positive and negative beliefs about light cigarettes and
      potential reduced exposure products (PREPs) among college student smokers and non
      smokers. METHODS: A web-based survey conducted in October-November 2004 among 424
      students rating 5 advertisements for cigarette brands (Marlboro Red, Light, and
      Ultralight; Quest; Eclipse) on 28 items tapping positive and negative product
      expectancies. RESULTS: Marlboro Light and Ultralight were rated more positively
      and less negatively than their Red counterpart. PREPs showed low positive and
      negative ratings relative to Marlboro Light. Positive expectancies were
      significantly related to willingness to try each brand. CONCLUSIONS: Advertising
      plays a role in influencing how college students view light and PREP cigarette
      brands.

PMID- 17511576
TI  - Factors predicting behavioral response to a physical activity intervention among
      adolescent females.
AB  - OBJECTIVE: To determine whether individual factors influenced rates of physical
      activity change in response to a school-based intervention. METHODS: Sedentary
      adolescent females (N = 63) participated in a 9-month physical activity program.
      Weekly levels of leisure-time physical activity were reported using an
      interactive website. RESULTS: Change in vigorous activity was more positive among
      participants who had higher fitness and lower friend support at baseline. Change
      in moderate activity was more positive among participants who had lower fitness
      and external barriers, and higher internal barriers at baseline. CONCLUSIONS:
      Adolescent females responded differentially to a physical activity intervention
      depending on individual characteristics.

PMID- 17511577
TI  - Relationships of protective factors to stress and symptoms of illness.
AB  - OBJECTIVE: To examine relationships of work and individual protective factors to
      health outcomes. METHODS: Participants from 2 corporate samples completed
      measures of supervisor support, hardiness, coping, global stress, and symptoms of
      illness. RESULTS: Regression analyses indicated that higher scores on hardiness
      and approach coping and being male predicted lower scores on stress and symptoms
      of illness. Additionally, supervisor support predicted fewer symptoms of illness
      but did not have a spillover effect onto stress. CONCLUSIONS: Interventions that
      enhance individual protective factors primarily and work protective factors
      secondarily may be most effective in reducing stress and illness among employees.

PMID- 17511578
TI  - Socioeconomic factors and persistent racial disparities in childhood vaccination.
AB  - OBJECTIVE: To better understand the effects of socioeconomic factors on racial
      disparities in childhood vaccination. METHODS: The National Immunization Survey
      data collected in 1999-2003 among children 19-35 months of age were analyzed
      using chisquare tests for trends and logistic regression modeling. Statistical
      significance was based on P<0.05. RESULTS: When adjusted by mother's education
      and household income, racial disparities in childhood vaccination were
      substantially reduced. The adjustment for mother's education reduced the
      disparity only slightly, but the adjustment for household income had the greater
      impact. CONCLUSIONS: Research should examine socioeconomic differences across
      populations to better understand racial disparities in health.

PMID- 17511580
TI  - Cardiac hypertrophy: mechanisms and therapeutic opportunities.
AB  - Cardiac hypertrophy and heart failure are major causes of morbidity and mortality
      in Western societies. Many factors have been implicated in cardiac remodeling,
      including alterations in gene expression in myocytes, cardiomyocytes apoptosis,
      cytokines and growth factors that influence cardiac dynamics, and deficits in
      energy metabolism as well as alterations in cardiac extracellular matrix
      composition. Many therapeutic means have been shown to prevent or reverse cardiac
      hypertrophy. New concepts for characterizing the pathophysiology of cardiac
      hypertrophy have been drawn from various aspects, including medical therapy and
      gene therapy, or use of stem cells for tissue regeneration. In this review, we
      focus on various types of cardiac hypertrophy, defining the causes of
      hypertrophy, describing available animal models of hypertrophy, discussing the
      mechanisms for development of hypertrophy and its transition to heart failure,
      and presenting the potential use of novel promising therapeutic strategies
      derived from new advances in basic scientific research.

PMID- 17511581
TI  - From oxygen sensing to heart failure.

PMID- 17511582
TI  - Microarray studies of genomic oxidative stress and cell cycle responses in
      obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA), the commonest form of sleep-disordered breathing,
      is characterized by recurrent episodes of intermittent hypoxia and sleep
      fragmentation. This study evaluated microarray measures of gene transcript levels
      in OSA subjects compared to age and BMI matched healthy controls. Measurements
      were obtained before and after: (a) a night of normal sleep in controls; and (b)
      a night of untreated apnea in OSA patients. All subjects underwent full
      polysomnography. mRNA from the whole blood samples was analyzed by HG-U133A and B
      Affymetrix GeneChip arrays using Spotfire 7.2 data analysis platform. After sleep
      in OSA patients, changes were noted in several genes involved in modulation of
      reactive oxygen species (ROS), including heme oxygenase 1, superoxide dismutase 1
      and 2, and catalase. Changes were also observed in genes involved in cell growth,
      proliferation, and the cell cycle such as cell division cycle 25B, signaling
      lymphocyte activating molecule (SLAM), calgizzarin S100A11, B-cell translocation
      gene, Src-like adapter protein (SLAP), and eukaryotic translation initiation
      factor 4E binding protein 2. These overnight changes in OSA patients are
      suggestive of activation of several mechanisms to modulate, and adapt to,
      increased ROS developing in response to the frequent episodes of intermittent
      hypoxia.

PMID- 17511583
TI  - Cytosolic NAD(P)H regulation of redox signaling and vascular oxygen sensing.
AB  - This article considers how regulation of signaling controlled by cytosolic NADPH
      and NADH redox systems contained within the vascular smooth muscle cell may
      contribute to coordinating alterations in force generation elicited by acute
      changes in oxygen tension. Additional important issues considered include
      defining when oxidases generating reactive oxygen species (ROS), such as Nox
      oxidases, or ROS metabolizing activities which utilize cytosolic NADH and/or
      NADPH are key participants in eliciting responses that are observed, and
      assessing how mitochondria can potentially contribute to the regulation that is
      seen. Many important signaling mechanisms potentially involved in vascular oxygen
      sensing such as potassium channels, systems regulating intracellular calcium, and
      the sensitivity of the contractile apparatus to calcium, and the control of cGMP
      mediated relaxation by soluble guanylate cyclase appear to be regulated by
      cytosolic NAD(P)H redox and or ROS. Differences in the processes controlling the
      maintenance of cytosolic NADPH redox by the pentose phosphate pathway of glucose
      metabolism are hypothesized to be a key factor in controlling the expression of a
      relaxation to hypoxia seen in systemic arteries compared to the hypoxic
      contractile response observed in pulmonary arterial smooth muscle.

PMID- 17511584
TI  - From oxygen sensing to heart failure: role of thioredoxin.
AB  - Oxidative stress has been widely recognized to be involved in the pathogenesis of
      cardiopulmonary disorders. In ischemic heart diseases, it is involved not only in
      the development of atherosclerosis but also in ongoing ischemic injury,
      especially in the reperfusion process. Cardiomyopathy is another cardiac disorder
      in which oxidative stress is involved. In diabetic cardiomyopathy, homocysteine,
      a well-known source of oxidative stress, is believed to play major roles in its
      development. Thioredoxin (TRX) is a redox-acting protein ubiquitously present in
      the human body. It also is inducible by a wide variety of oxidative stresses. TRX
      is a multifunctional protein and has anti-inflammatory and antiapoptotic effects,
      as well as antioxidative effects. It is therefore feasible to think that TRX is a
      potential therapy for cardiac disease. Moreover, serum TRX is a well-recognized
      biomarker of various diseases involving oxidative stress, and this is also the
      case for cardiac disorders. Here we discuss how TRX is useful as a biomarker of
      and therapeutic agent for cardiopulmonary disorders, especially focusing on
      ischemic heart disease, myocarditis and oxygen sensing, and acute respiratory
      distress syndrome.

PMID- 17511585
TI  - Clinical perspective of obstructive sleep apnea-induced cardiovascular
      complications.
AB  - Obstructive sleep apnea (OSA) syndrome is a highly prevalent disorder
      characterized by recurrent upper airway collapse during sleep, and associated
      with repetitive episodes of transient oxygen desaturation during sleep. It
      disrupts normal ventilation and sleep architecture, and is typically associated
      with excessive daytime sleepiness, snoring, and witnessed apneas. Besides being
      associated with neurocognitive impairment, mood and behavioral effects, and
      increased risk for work-related and traffic accidents, OSA has also been
      implicated in the pathogenesis of various cardiovascular diseases, including
      systemic hypertension, coronary artery disease, congestive heart failure,
      pulmonary hypertension, stroke, and cardiac arrhythmias. The mechanisms by which
      OSA affects the cardiovascular system may involve mechanical effects on
      intrathoracic pressure, increased sympathetic activation, intermittent hypoxia,
      and endothelial dysfunction. Therapy with continuous positive airway pressure
      (CPAP) has been demonstrated to improve cardiopulmonary hemodynamics in patients
      with OSA and may reverse the endothelial cell dysfunction.

PMID- 17511586
TI  - Clinical perspective of hypoxia-mediated pulmonary hypertension.
AB  - Pulmonary hypertension is a condition associated with a variety of pulmonary
      disorders whose common denominator is alveolar hypoxia. Such disorders include
      chronic obstructive pulmonary disease, pulmonary fibrosis, sleep-disordered
      breathing, and exposure to high altitude. Acute hypoxia is characterized by
      vasoconstriction of small pulmonary arteries, a phenomenon called hypoxic
      pulmonary vasoconstriction. With prolonged hypoxia, thickening of the smooth
      vascular layer of the small pulmonary arteries occurs, a phenomenon described as
      pulmonary vascular remodeling. Although the core mechanisms of both
      vasoconstriction and remodeling are thought to reside in the smooth muscle cell
      layer, the endothelium modulates these two processes. The purpose of this review
      is briefly to (a) discuss the mechanisms of hypoxic pulmonary hypertension as it
      pertains to certain disease states, and (b) examine the pathways that have
      potential therapeutic applications for this condition.

PMID- 17511587
TI  - Effects of intermittent hypoxia on the heart.
AB  - Obstructive sleep apnea (OSA) is associated with cardiovascular diseases such as
      hypertension through mechanisms involving intermittent hypoxia (IH). However, it
      is not yet clear whether IH directly affects the heart. In a mouse model of OSA,
      we found that IH causes time-dependent alterations of the susceptibility of the
      heart to oxidative stress. Acute IH can exert preconditioning-like
      cardioprotection, in part, through the transcriptional activation of genes such
      as bcl-x(L) and gata4. We cloned the mouse gata4 promoter and identified an IH
      responsive region. The exposure of mice to prolonged IH results in the increased
      susceptibility of the heart to ischemia-reperfusion injury by increasing the
      oxidative stress status. This might resemble conditions of OSA patients. In our
      mouse model, further exposure to prolonged IH allowed reversal of the enhancement
      of myocardial damage. Understanding the complex effects of IH on the heart should
      help ultimately to develop therapeutic strategies against OSA-induced
      complications.

PMID- 17511588
TI  - VEGF signaling through NADPH oxidase-derived ROS.
AB  - Angiogenesis is a key process involved in normal development and wound repair, as
      well as ischemic heart and limb diseases, and atherosclerosis. Vascular
      endothelial growth factor (VEGF), a potent angiogenesis factor, stimulates
      proliferation, migration, and tube formation of endothelial cells (ECs),
      primarily through the VEGF receptor type2 (VEGFR2). Reactive oxygen species (ROS)
      function as signaling molecules to mediate biological responses. In ECs, NADPH
      oxidase is one of the major sources of ROS and consists of catalytic subunits
      (Nox1, Nox2, and Nox4), p22phox, p47phox, p67phox, and the small GTPase Rac1.
      VEGF stimulates ROS production via activation of gp91phox (Nox2)-based NADPH
      oxidase, and ROS are involved in VEGFR2-mediated signaling linked to EC migration
      and proliferation. Moreover, ROS derived from NADPH oxidase are involved in
      postnatal angiogenesis. Localizing NADPH oxidase and its regulators at the
      specific subcellular compartment is an important mechanism for activating
      specific redox signaling events. This review focuses on a role of NADPH oxidase
      derived ROS in angiogenesis and critical regulators involved in generation of
      spatially and temporally restricted ROS-dependent VEGF signaling at leading edge,
      focal adhesions/complexes, caveolae/lipid rafts, and cell-cell junctions in ECs.
      Understanding these mechanisms should facilitate the development of new
      therapeutic strategies to modulate new blood vessel formation.

PMID- 17511589
TI  - Hypoxia and the lung: beyond hypoxic vasoconstriction.
AB  - This article extends the influence and effects of hypoxia on the lung beyond
      vasoconstriction and regional blood flow control. Clearly, hypoxia, via the
      transcription factor hypoxia-inducible factor (HIF)-1alpha, induces a large
      number of genes encoding proteins, which control cellular metabolism and growth
      and also participate in inflammation. Hypoxia, likely via vascular endothelial
      growth factor (VEGF), recruits bone marrow precursor cells to the lung and
      affects the behavior of immune cells. How hypoxia shapes immune responses through
      VEGF and its receptors on mast cells, eosinophils, and dendritic cells and
      through lung endothelial cell/lymphocyte interactions will be a productive area
      for future research.

PMID- 17511590
TI  - Oxygen sensing in the carotid body and its relation to heart failure.
AB  - This brief review first touches on the origins of the earth's oxygen. It then
      identifies and locates the principal oxygen sensor in vertebrates, the carotid
      body (CB). The CB is unique in that in human subjects, it is the only sensor of
      lower than normal levels in the partial pressure of oxygen (hypoxia, HH). Another
      oxygen sensor, the aortic bodies, are mostly vestigial in higher vertebrates. At
      least they play a much smaller role than the CB. In such an important role, the
      many reflexes in response to CB stimulation by HH are presented. After briefly
      reviewing what CB stimulation does, the next topic is to describe how the CB
      chemotransduces HH into neural signals to the brain. Several mechanisms are
      known, but critical steps in the mechanisms of chemosensation and
      chemotransduction are still under investigation. Finally, a brief glance at the
      operation of the CB in chronic heart failure patients is presented. Specifically,
      the role of nitric oxide, NO, is discussed.

PMID- 17511591
TI  - Could heme-oxygenase-1 have a role in modulating the recipient immune response to
      embryonic stem cells?
AB  - Pluripotent human embryonic stem cells (hESCs) may provide a potential source of
      cellular therapies, but as allogeneic cells may require evading the recipient's
      immune response. Using an NIH-registry hESC line, it was found that
      undifferentiated hESCs induce a reduced proliferative response compared to PBMC
      and demonstrate that this diminished response correlates with the activity of
      heme oxygenase-1 (HO-1). Inhibition of HO-1 significantly increases T cell
      proliferation against hESC, indicating the potential suppression of these cells
      during transplantation of allogeneic hESC. These data suggest the hypothesis that
      HO-1 provides a mechanism for protecting hESCs in vivo.

PMID- 17511592
TI  - Does nitric oxide contribute to progressive cardiac tissue damage and dysfunction
      after infarction?
AB  - Myocardial infarction induces contractile dysfunction and remodeling that can
      lead to heart failure. Nitric oxide has been proposed as one of the major actors
      of this pathophysiologic process. We note that N (G)-nitro-L-arginine methyl
      ester (L-NAME) administration from day 2 to day 7 after myocardial infarction in
      rats improves stroke volume, preserves cardiac compliance, and reduces infarct
      expansion. Our observations lead to the hypothesis that the mechanisms by which
      cytokines contribute to myocardial remodeling and dysfunction in the days after
      infarction might involve *NO signalling pathways.

PMID- 17511593
TI  - Relationship of flow rate, uric acid, peroxidase, and superoxide dismutase
      activity levels with complications in diabetic patients: can saliva be used to
      diagnose diabetes?
AB  - Can salivary free radicals and antioxidant parameters be useful in general
      diagnosis and evaluation of diabetes mellitus Type II (DM)? Serum and salivary
      redox state of 40 diabetes mellitus patients were examined and compared with 20
      controls. The involvement of salivary gland in diabetes mellitus has been
      suggested based on salivary flow rate and compositional alterations. In addition,
      the redox state of saliva of diabetes mellitus patients is different than that of
      normoglycemic control human subjects. This observation unveils the opportunity to
      use noninvasive saliva-based diagnostics for diabetes mellitus patients.

PMID- 17511594
TI  - Feasibility of a randomized controlled trial testing nifedipine vs. placebo for
      the treatment of preterm labor.
AB  - AIMS: Nifedipine is believed to be a superior tocolytic agent on the basis of
      efficacy and side-effect profile, but was never prospectively evaluated in a
      placebo-controlled randomized clinical trial (RCT). In our study, we sought to
      identify limitations in participation for a would-be RCT comparing nifedipine to
      placebo. METHODS: A prospective feasibility study was conducted at Ste-Justine
      Hospital, a tertiary care center, on women between 24 and 34 weeks' gestation,
      presenting to the labor and delivery room with obstetrical complaints. Patient
      information was collected and would-be participants were identified on the basis
      of pre-established clinical and ultrasound criteria as well as on willingness to
      participate, as determined by the study research nurse. RESULTS: During a 6-month
      period, 483 women presenting with signs and symptoms of preterm labor (PTL) were
      eligible for further evaluation. A total of 321 (66.5%) women were excluded for
      obstetrical and medical reasons whereas 125 (25.9%) did not meet strict inclusion
      criteria (cervical length <25 mm or positive fetal fibronectin). When using
      strict criteria, only 37 women (7.6%) were found to be eligible for study
      participation. Subject willingness to participate as assessed by the research
      nurse was 50%. CONCLUSIONS: If adhering to strict inclusion/exclusion criteria,
      the feasibility of an appropriately sampled RCT testing tocolytic therapy against
      a placebo would require a large concerted multicenter effort to meet sample size
      demands.

PMID- 17511595
TI  - Lessons learned from four advanced abdominal pregnancies at an East African
      Health Center.
AB  - AIMS: To analyze diagnosis and treatment of four advanced abdominal pregnancies
      in a low-resource setting of a developing country. METHODS: Extrauterine
      pregnancies occurring between 1997 and 2003 were identified from hospital records
      of the Mikumi Health Center in Tanzania/East Africa. RESULTS: A total of 45
      extrauterine pregnancies were diagnosed four of which were advanced and located
      in the abdominal cavity. At the time of diagnosis, pregnancies were at 33, 34, 36
      and 39 weeks of gestation, respectively. All four mothers survived but three of
      four fetuses died. One child is alive and well three years after delivery.
      CONCLUSION: Abdominal pregnancy is rather difficult to detect in a low-resource
      setting of a developing country. Persistent abdominal pain and tenderness, as
      well as fetal movements in the upper abdomen associated with abnormal fetal lie,
      may lead to its diagnosis. Localizing the fetal heart sounds in the maternal
      epigastrium especially in patients with abdominal pain may also be helpful in
      diagnosing an abdominal pregnancy. In addition, the lack of cervical changes or a
      displaced cervix should lead to the suspicion of an abdominal pregnancy.

PMID- 17511596
TI  - Umbilical cord blood collection: do patients really understand?
AB  - BACKGROUND: Pregnant patients have the option of storing their infant's cord
      blood with a private/commercial company for possible future use by the child or
      other family members. Some patients also have the option to donate the cord blood
      to a public bank for anyone to use. We evaluated patient understanding about cord
      blood banking in a cohort of patients with access to both options. METHODS:
      Anonymous questionnaires were collected from 325 pregnant patients seen in our
      Antepartum Testing Unit. RESULTS: Compared to those donating to a public bank,
      women planning on storing with a private/commercial company were less likely to
      believe that a suitable donor could be found from a public cord blood bank. Women
      had a strikingly poor understanding regarding the current uses for cord blood
      therapy. When asked whether cord blood has been used successfully to treat
      Alzheimer's disease, Parkinson's disease, and spinal cord injury only 28%, 24%,
      and 24%, respectively, correctly knew that it had not. CONCLUSIONS: Obstetricians
      should assume that pregnant women are poorly informed about cord blood banking.
      The decision making process should be conducted with the goal of ensuring every
      pregnant woman the opportunity to make a well informed decision about cord blood
      banking.

PMID- 17511597
TI  - Role of visfatin, insulin-like growth factor-I and insulin in fetal growth.
AB  - OBJECTIVE: IGF-I and insulin are the main regulators of intrauterine and
      postnatal growth. Adipose tissue secreted cytokines are implicated in
      intrauterine growth. The relevant function of the adipocytokine visfatin is
      unknown. MATERIALS AND METHODS: Serum visfatin, IGF-I and insulin levels were
      measured by enzyme immunoassays in 40 singleton full-term fetuses and neonates on
      postnatal days 1(N1) and 4 (N4). RESULTS: No significant correlations exist
      between visfatin and IGF-I or insulin. N1 and N4 visfatin positively correlated
      with customized (adjusted) birth weight centiles (r=0.511, P=0.021, and r=0.597,
      P=0.005, respectively). Fetal and N1 IGF-I positively correlated with customized
      centiles (r=0.608, P<0.001 and r=0.485, P=0.006, respectively). Fetal insulin
      positively correlated with customized centiles (r=0.654, P=0.021). CONCLUSIONS:
      Potential implication of visfatin in fetal growth is probably not mediated by IGF
      I or insulin. Although a more active role cannot be excluded, visfatin may simply
      represent a marker of fat accumulation.

PMID- 17511598
TI  - Sequela of preterm versus term infants born to mothers on a methadone maintenance
      program: differential course of neonatal abstinence syndrome.
AB  - OBJECTIVE: We determined the effect of preterm delivery on the course of neonatal
      abstinence syndrome (NAS) in infants born to mothers participating in a methadone
      maintenance program. STUDY DESIGN: A retrospective cohort study was conducted in
      which infant and maternal data were collected from the medical records of 53
      preterm and 66 term infants. Infants were selected from all infants admitted to
      Thomas Jefferson University hospital born between 1998 and 2002 whose mothers
      were enrolled in the methadone maintenance program. All infants were managed by a
      standard protocol utilizing the Neonatal Abstinence Scoring System (NASS) and
      neonatal opiate solution (NOS). Preterm and term infants were compared. RESULTS:
      Preterm infants had shorter lengths of stay, treatment courses and required less
      medication than did term infants during the same time period. CONCLUSION: These
      data indicate that following exposure to maternal methadone, preterm infants have
      a different neonatal course than do infants born at term.

PMID- 17511599
TI  - Genetic aspects of floral fragrance in plants.
AB  - It is generally assumed that compounds are emitted from flowers in order to
      attract and guide pollinators. Due to the invisibility and the highly variable
      nature of floral scent, no efficient and reliable methods to screen for genetic
      variation have been developed. Moreover, no convenient plant model systems are
      available for flower scent studies. In the past decade, several floral fragrance
      related genes have been cloned; the biosynthesis and metabolic engineering of
      floral volatiles have been studied with the development of biotechnology. This
      review summarizes the reported floral fragrance-related genes and the
      biosynthesis of floral scent compounds, introduces the origin of new modification
      enzymes for flower scent, compares different methods for floral fragrance-related
      gene cloning, and discusses the metabolic engineering of floral scent. Finally,
      the perspectives and prospects of research on floral fragrance are presented.

PMID- 17511600
TI  - Polyglutamine-mediated neurodegeneration: use of chaperones as prevention
      strategy.
AB  - Polyglutamine diseases are a class of inherited neurodegenerative disorders
      caused by the expansion of a polyglutamine tract within the respective proteins.
      Clinical studies have revealed that the forming of neuronal intranuclear
      inclusions by the disease protein is a common pathological feature of
      polyglutamine diseases. Although there has been considerable progress in
      understanding polyglutamine diseases, many questions regarding their mechanism
      are still unanswered. The finding that molecular chaperones are associated with
      ubiquitinated intranuclear inclusions clearly indicates a crucial role of
      molecular chaperones in the generation of these fatal diseases. Molecular and
      chemical chaperones have been found to be a good agent for suppressing many
      polyglutamine diseases in several animal models. In this review, I discuss the
      roles of the ubiquitin-proteasome pathway and molecular chaperones in the
      development of polyglutamine diseases and probable approach for the prevention of
      many of these fatal disorders using molecular chaperones as a therapeutic agent.
      Newly found chemical chaperones have been demonstrated to be potentially useful
      and could be used as a therapeutic strategy in preventing many versions of
      polyglutamine diseases.

PMID- 17511601
TI  - Enzymes phosphorylating lipids and polysaccharides.
AB  - Phosphorylation plays an important role in regulation of living functions of
      organisms; phosphorylation may significantly alter chemical properties of
      proteins, lipids, and carbohydrates. Canonical kinases catalyze transfer of
      terminal phosphate group from ATP (or other NTPs) to specific nucleophilic groups
      of proteins, lipids, and polysaccharides. Recently, unique kinases, catalytically
      active antibodies (abzymes) phosphorylating proteins, lipids, and polysaccharides
      have also been discovered. This review highlights biological functions and
      enzymatic characteristics of canonical kinases and abzymes phosphorylating lipids
      and polysaccharides.

PMID- 17511602
TI  - Corrected equations for calculation of constants in enzyme inhibition and
      activation.
AB  - Equations for calculation of the constants of biparametrical types of enzyme
      inhibition and activation were obtained that take into account a ratio of the
      lengths of L vector projections representing such reactions in the three
      dimensional K (m)V I coordinate system. This allows higher accuracy of
      calculation and is more correct for comparison of these constants. Examples of
      data analysis of enzyme inhibition and activation by using the traditional
      equations (they do not take into account the lengths of vector projections) and
      corrected ones (they take into account the lengths of vector projections) are
      given. The corrected and traditional equations are used for calculation of the
      constants of biparametrical types of enzyme inhibition and activation.

PMID- 17511603
TI  - Location and volume of the active site of chymotrypsin.
AB  - The active site of chymotrypsin molecule (approximated by a sphere with radius of
      20 A) was taken as the largest cavity on the enzyme surface. The volume inside
      the approximating sphere is sufficient for placement of 95% of non-hydrogen atoms
      of the enzyme. The active site cavity is localized in a spherical sector with
      solid angle of 80 degrees whose axis passes through the CB-atom of the Ser195
      residue. The volume of the active site cavity is about 2700 A(3) (8% of the
      volume of the approximating sphere) as computed by the Monte-Carlo method from
      known X-ray data. The size and shape of the active site cavity is sufficient for
      entrance of significantly large fragments (more than 60 non-hydrogen atoms) of
      the substrate molecule. At the active site cavity bottom, there is a narrow
      compartment adjacent to an oxy-anion hollow and accessible to water but not to
      substrate molecules. The water molecules inside this narrow compartment can take
      part in heat exchange with the external medium during different steps of the
      enzymatic process.

PMID- 17511604
TI  - Specific biochemical features of replication of clinical influenza viruses in
      human intestinal cell culture.
AB  - Influenza A viruses isolated from the respiratory tract of patients with
      influenza were cultured in human intestinal epithelium cells (CACO-2 line). The
      CACO-2 cells were found to be 100-fold more susceptible to the clinical viruses
      than MDCK cells and chicken embryos. On passaging in CACO-2 cells, clinical
      isolates of the subtype H3N2 retained the original "human" phenotype and
      agglutinated human but not chicken erythrocytes, whereas on passaging in MDCK
      cells the virus phenotype changed to the "avian" one. On comparison with
      laboratory strains (grown in chicken embryos or MDCK cells), the clinical viruses
      were characterized by higher stability of the anti-interferon protein NS1 but had
      a reduced synthesis of the matrix protein M1, and this could facilitate the virus
      adaptation and escape of the infected cells from immune attack in the human body.
      The increased tropism to the human CACO-2 cells correlated with higher adsorption
      of the clinical viruses on cellular receptors. However, in the CACO-2 and MDCK
      cells the ratio of sialyl-containing glycoreceptors of the 2-3 and 2-6 type was
      similar. These observations indicated that not only sialic acid residues were
      involved in the adsorption and penetration of the clinical viruses into human
      cells, but also the protein moiety of the cellular receptor itself and/or an
      additional cellular coreceptor. Thus, clinical influenza viruses are shown to
      possess a specific mechanism of sorption and entry into human epithelial cells,
      which is responsible for their higher tropism to human cells and is unlike such a
      mechanism in canine cells.

PMID- 17511605
TI  - Interaction of ceruloplasmin, lactoferrin, and myeloperoxidase.
AB  - When lactoferrin (LF) and myeloperoxidase (MPO) are added to ceruloplasmin (CP),
      a CP-LF-MPO triple complex forms. The complex is formed under physiological
      conditions, but also in the course of SDS-free PAGE. Polyclonal antibodies to
      both LF and MPO displace the respective proteins from the CP-LF-MPO complex.
      Similar replacement is performed by a PACAP38 fragment (amino acids 29-38) and
      protamine that bind to CP. Interaction of LF and MPO with CP-Sepharose is blocked
      at ionic strength above 0.3 M NaCl and at pH below 4.1 (LF) and 3.9 (MPO). Two
      peptides (amino acids 50-109 and 929-1012) were isolated by affinity
      chromatography from a preparation of CP after its spontaneous proteolytic
      cleavage. These peptides are able to displace CP from its complexes with LF and
      MPO. Both human and canine MPO could form a complex when mixed with CP from seven
      mammalian species. Upon intravenous injection of human MPO into rats, the rat CP
      human MPO complex could be detected in plasma. Patients with inflammation were
      examined and CP-LF, CP-MPO, and CP-LF-MPO complexes were revealed in 80 samples
      of blood serum and in nine exudates from purulent foci. These complexes were also
      found in 45 samples of serum and pleural fluid obtained from patients with
      pleurisies of various etiology.

PMID- 17511606
TI  - Structural principles of the wide substrate specificity of Thermoactinomyces
      vulgaris carboxypeptidase T. Reconstruction of the carboxypeptidase B primary
      specificity pocket.
AB  - Site-directed mutagenesis in the active site of Thermoactinomyces vulgaris
      carboxypeptidase T (CpT), which is capable of hydrolyzing both hydrophobic and
      positively charged substrates, resulted in five mutants: CpT1 (A243G), CpT2
      (D253G/T255D), CpT3 (A243G/D253G/T255D), CpT4 (G207S/A243G/D253G/T255D), and CpT5
      (G207S/A243G/T250A/D253G/T255D). These mutants step-by-step reconstruct the
      primary specificity pocket of carboxypeptidase B (CpB), which is capable of
      cleaving only positively charged C-terminal residues. All of the mutants retained
      the substrate specificity of the wild-type CpT. Based on comparison of three
      dimensional structures of CpB and the CpT5 model, it was suggested that the lower
      affinity of CpT5 for positively charged substrates than the affinity of CpB could
      be caused by differences in nature and spatial location of Leu247 and Ile247 and
      of His68 and Asp65 residues in CpT and CpB, respectively, and also in location of
      the water molecule bound with Ala250. An additional hydrophobic region was
      detected in the CpT active site formed by Tyr248, Leu247, Leu203, Ala243, CH3
      group of Thr250, and CO-groups of Tyr248 and Ala243, which could be responsible
      for binding hydrophobic substrates. Thus, notwithstanding the considerable
      structural similarity of CpT and pancreatic carboxypeptidases, the mechanisms
      underlying their substrate specificities are different.

PMID- 17511607
TI  - Preparation of functionally active recombinant human interleukin-6.
AB  - The gene of human interleukin-6 (hIL-6) with an additional 20 amino acids on the
      N-end, including six histidine residues, was cloned into the expression plasmid
      pET28b(+). The conditions were elaborated for preparing highly active protein
      both using denaturing agents and without them. Application of a dialysis cascade
      allowed us to prepare a functionally active hIL-6 of 90-95% purity with the yield
      of 3 mg from liter of the cell culture. The highest activity was detected by
      ELISA in the preparation obtained without denaturing agents. The functional
      activity of hIL-6 was studied by flow cytofluorimetry. Addition of hIL-6 to the
      cells of immortal lines of human multiple myeloma resulted in dimerization of the
      gp130 receptor molecule.

PMID- 17511608
TI  - Purification and primary structure of novel lipid transfer proteins from
      germinated lentil (Lens culinaris) seeds.
AB  - A subfamily of eight novel lipid transfer proteins designated as Lc-LTP1-8 was
      found in the lentil Lens culinaris. Lc-LTP2, Lc-LTP4, Lc-LTP7, and Lc-LTP8 were
      purified from germinated lentil seeds, and their molecular masses (9268.7,
      9282.7, 9121.5, 9135.5 daltons) and complete amino acid sequences were
      determined. The purified proteins consist of 92-93 amino acid residues, have four
      disulfide bonds, and inhibit growth of Agrobacterium tumefaciens. Total RNA was
      isolated from germinated lentil seeds, RT-PCR and cloning were performed, and the
      cDNAs of six LTPs were sequenced. Precursor 116-118-residue proteins with 24-25
      residue signal peptides were found, and two of them are purified proteins Lc-LTP2
      and Lc-LTP4.

PMID- 17511609
TI  - Overexpression of complexin in PC12 cells inhibits exocytosis by preventing SNARE
      complex recycling.
AB  - Complexin is an important protein that functions during Ca2+-dependent
      neurotransmitter release. Substantial evidence supports that complexin performs
      its role through rapid interaction with SNARE complex with high affinity.
      However, alpha-SNAP/NSF, which can disassemble the cis-SNARE complex in the
      presence of MgATP, competes with complexin to bind to SNARE complex. In addition,
      injection of alpha-SNAP into chromaffin cells enhances the size of the readily
      releasable pool, and mutation disrupting the ATPase activity of NSF results in
      the accumulation of SNARE complex. Thus, whether high concentrations of complexin
      could result in a reverse result is unclear. In this paper, we demonstrate that
      when stably overexpressed in PC12 cells, high levels of complexin result in the
      accumulation of SNARE complex. This in turn leads to a reduction in the size of
      the readily releasable pool of large dense core vesicles. These results suggest
      that high levels of complexin seem to prevent SNARE complex recycling, presumably
      by displacing NSF and alpha-SNAP from SNARE complex.

PMID- 17511610
TI  - Lactoferrin from canine neutrophils: isolation and physicochemical and
      antimicrobial properties.
AB  - Lactoferrin has been isolated from canine leukocytes for the first time.
      Lactoferrin was identified by N-terminal amino acid sequence and by capability to
      capture ferric cations resulting in a complex with absorbance maximum at 460-470
      nm. It is demonstrated that canine lactoferrin resembles the human homolog in
      some physicochemical properties, i.e. molecular weight, carbohydrate presence,
      and conditions of protein-iron complex dissociation. Bactericidal activity of dog
      lactoferrin was demonstrated on the gram-negative bacterium Escherichia coli and
      gram-positive bacterium Listeria monocytogenes. Bactericidal activity of canine
      lactoferrin is similar to that of human lactoferrin.

PMID- 17511611
TI  - Isolation and characterization of proteoglycans synthesized by rat myoblasts L6J1
      in culture.
AB  - Proteoglycans synthesized by rat myoblasts L6J1 in culture were isolated using
      sorbent Q-Sepharose from culture medium, extracellular matrix (ECM), and cells.
      Elution of the sorbed material in a NaCl gradient separated proteoglycans from
      the bulk of proteins eluted at low concentration of the salt. Four fractions
      (fractions I-IV) were obtained for each component of the cell culture, including
      two proteoglycan fractions for the ECM and culture medium and one fraction for
      the myoblasts. Proteoglycans of the culture medium were virtually completely
      represented by proteoglycans of fetal calf serum. With enzymes chondroitinase ABC
      and heparinase III chondroitin/dermatan sulfate proteoglycans were shown to
      prevail in all components of the myoblast culture. The core proteins of
      proteoglycans were characterized by electrophoresis.

PMID- 17511612
TI  - Purification and characterization of a subtilisin-like proteinases secreted in
      the stationary growth phase of Bacillus amyloliquefaciens H2.
AB  - Proteinases secreted during the early and late stationary phases have been
      isolated from the culture liquid of Bacillus amyloliquefaciens H2 using CM
      cellulose ion-exchange chromatography with subsequent FPLC on a Mono S column.
      Considering the character of hydrolysis of specific chromogenic substrates and
      the type of inhibition, these enzymes were identified as subtilisin-like
      proteinases. The molecular weight of both proteinases is 29 kD. The proteolytic
      activity of the proteinases secreted during the early and late stationary phases
      towards the synthetic substrate Z-Ala-Ala-Leu-pNA was maximal at pH 8.5 and 9.0,
      respectively. The maximal activity of both proteinases was observed at 37 degrees
      C, and the proteins were stable within the pH range of 7.2-9.5. The subtilisin
      like proteinases from B. amyloliquefaciens were shown to catalyze synthesis of
      peptide bonds.

PMID- 17511613
TI  - Depression.

PMID- 17511614
TI  - The CRF1 receptor, a novel target for the treatment of depression, anxiety, and
      stress-related disorders.
AB  - The present review focuses on the corticotropin releasing factor type 1 (CRF(1))
      receptor as a novel target for treating depression, anxiety and other stress
      related disorders. An organism's stress response system is a complex network of
      neuronal, endocrine and autonomic pathways which has evolved to provide adaptive
      reactions to severe environmental and physiological stressors. The peptide CRF
      plays a critical role in the proper functioning of the stress response system
      through its actions on CRF(1) receptors located at multiple anatomical sites.
      Clinical data indicate that dysfunctions of the stress response system, expressed
      as excessive CRF activity and possible hyperstimulation of CRF(1) receptors, are
      present in a range of stress-related disorders, including depression, anxiety,
      and irritable bowel syndrome. CRF(1) dysfunction may be particularly prominent in
      severe forms of these disorders (e.g. melancholic or psychotic depression,
      comorbid conditions, chronic posttraumatic stress disorder) and/or when these
      disorders are accompanied by a history of exposure to early life trauma.
      Available clinical data support the potential therapeutic efficacy of
      pharmacological agents which block the CRF(1) receptor. Preclinical studies
      demonstrate that CRF(1) receptor antagonists are efficacious in animal models in
      which CRF pathways and CRF(1) receptors are hyperactivated, whereas they tend to
      be quiescent in states of low basal CRF activity, indicative of potentially
      reduced side effects in humans. Symptom diversity in animal models of stress and
      in human stress disorders may result from dysfunctions in different CRF(1)
      receptor populations and/or different functional states of the CRF(1) receptor.
      Small molecule, orally-active CRF(1) receptor antagonists may be a broadly useful
      approach for treating a range of stress-related disorders that are associated
      with excessive CRF(1) receptor stimulation.

PMID- 17511615
TI  - The brain galanin receptors: targets for novel antidepressant drugs.
AB  - Our present view that the mood disorders involve dysfunction of monoaminergic
      system is a result of important clinical and preclinical observations over the
      past 40 years. The therapeutic efficacy of drugs such as the tricyclic
      antidepressants (TCAs), monoamine oxidase inhibitors, selective serotonin
      reuptake inhibitors (SSRIs) and lately of SNRIs (serotonin and norepinephrine
      reuptake inhibitors) helped to shape our view that mood regulation involves the
      monoaminergic systems in some way. It is thus little surprising when the
      neuropeptide, galanin, is discovered to coexist with norepinephrine (NE) in locus
      coeruleus (LC) neurons and with serotonin (5-HT) in the dorsal raphe nucleus
      (DRN) neurons, a link between galanin mediated signaling and mood regulation is
      sought. Galanin receptors are expressed in brain structures that are involved in
      the regulation of mood such as frontal cortex, amygdala, hypothalamus, LC, DRN
      and hippocampus. It is almost an accident of research fate that the potent
      effects of galanin on cognitive performance and seizure threshold have led
      galanin research to focus on the hippocampus where the neuropeptide is present in
      cholinergic and noradrenergic afferents and where the receptor density is much
      lower than in the monoaminergic nuclei. Hopefully it is not too late to report on
      the recent inroads into the roles of galanin and of galanin receptor subtypes 2
      and 3 (GalR2 and GalR3) in mood regulation in animal models as well as in human
      patients with major depression. A body of existing data suggests that GalR2
      signaling leads to antidepressant-like, anticonvulsant and neurogenesis-promoting
      effects, a spectrum of activities that are commonly associated with efficacious
      antidepressants. Similarly, GalR3 antagonists exhibit anxiolytic and
      antidepressant-like activity, another clinically useful combination for the
      treatment of mood disorders. Since both GalR2 and GalR3 are G-protein coupled
      receptors (GPCRs), a favorite target class for drug development, we believe that
      the pace of developing galaninergic antidepressants will increase significantly
      from now on.

PMID- 17511616
TI  - Targeting signal transduction pathways in the treatment of mood disorders: recent
      insights into the relevance of the Wnt pathway.
AB  - Regulation of complex signaling pathways plays a critical role in higher-order
      brain functions including the regulation of mood, cognition, appetite, sexual
      arousal, sleep patterns, and weight, all of which are altered in mood disorders,
      suggesting the involvement of signaling pathways in mood disorder pathogenesis
      and pathophysiology. Most existing medications used to treat mood disorders take
      many weeks to exert their full clinical effects, a fact which implicates changes
      in gene and protein expression, as well as neuroplasticity, in their mechanism of
      action. Modulation of signaling pathways has many downstream effects on gene
      expression and protein function, causing changes in synaptic function,
      plasticity, and response to various inputs such as neurohormones. The Wnt
      signaling pathway has recently been linked to the therapeutically relevant
      actions of available treatments of mood disorders. We provide a brief
      introduction to signaling cascades and their potential roles in mood disorder
      pathophysiology and treatment. Subsequently, we describe the Wnt signaling
      pathway, and glycogen synthase kinase-3 (GSK-3) and beta-catenin specifically,
      discussing studies that have implicated these proteins as relevant to the
      pathophysiology and treatment of mood disorders. Future directions, aimed at
      understanding mood disorders and developing more efficacious treatments, are also
      discussed.

PMID- 17511617
TI  - Adult hippocampal neurogenesis as target for the treatment of depression.
AB  - The dentate gyrus (DG) is one of only two brain structures known to retain the
      ability to produce new neurons in adulthood. The functional significance of adult
      neurogenesis in the DG is not yet well understood, but recent evidence has
      implicated adult neurogenesis in the etiology and treatment of depression.
      Elevated stress hormone levels, which are present in some depressed patients and
      can precipitate the onset of depression, reduce neurogenesis in animal models.
      Conversely, virtually all antidepressant treatments studied to date, including
      drugs of various classes, electroconvulsive therapy, and behavioral treatments,
      increase neurogenesis in the DG. We critically review this literature linking DG
      neurogenesis with depression, looking to both animal and human studies. We
      conclude that a reduction in neurogenesis by itself is not likely to produce
      depression. However, at least some therapeutic effects of antidepressant
      treatments appear to be neurogenesis-dependent. We review the cellular pathways
      through which antidepressant drugs boost neurogenesis and present several
      hypotheses about how DG neurogenesis may be instrumental in the therapeutic
      effects of these drugs.

PMID- 17511619
TI  - A novel murine protein with no effect on iron homoeostasis is homologous with
      transferrin and is the putative inhibitor of carbonic anhydrase.
AB  - In a search for genes that modify iron homoeostasis, a gene (1300017J02Rik) was
      located immediately upstream of the murine TF (transferrin) gene. However,
      expression of the 1300017J02Rik gene product was not responsive to a number of
      modulators of iron metabolism. Specifically, expression was not altered in mouse
      models of iron disorders including mice with deficiencies in the haemochromatosis
      protein Hfe, the recombination-activating protein, Rag, beta2-microglobulin, TF,
      ceruloplasmin or Hb, or in mice with microcytic anaemia. Additionally, neither
      lipopolysaccharide nor hypoxia treatment resulted in any significant changes in
      the 1300017J02Rik expression level. The genomic DNA sequence suggested that the
      1300017J02Rik gene product might be a protein equivalent to the pICA {porcine ICA
      [inhibitor of CA (carbonic anhydrase)]}. The coding region for the murine
      1300017J02Rik gene was placed into the pNUT expression vector. Transformed BHK
      cells (baby-hamster kidney cells) were transfected with this plasmid, resulting
      in secretion of recombinant mICA (murine ICA) into the tissue culture medium.
      Following purification to homogeneity, the yield of mICA from the BHK cells was
      found to be considerably greater (at least 4-fold) than the yield of pICA from a
      previously reported Pichia pastoris (yeast) expression system. MS showed that the
      recombinant mICA was a glycoprotein that associated with CA in a 1:1
      stoichiometry. Despite its high sequence similarity to TF, titration experiments
      showed that mICA was unable to bind iron specifically. Although enzymatic assays
      revealed that mICA was able to inhibit CA, it is unclear if this is its sole or
      even its major function since, to date, humans and other primates appear to lack
      functional ICA. Lastly, we note that this member of the TF superfamily is a
      relatively recent addition resulting from a tandem duplication event.

PMID- 17511621
TI  - Introduction to the Biochemical Society Focused Meeting on Diet and
      Cardiovascular Health: chylomicron remnants and their emerging roles in vascular
      dysfunction in atherosclerosis.
AB  - Although it has been known for many years that dietary lipids influence the
      development of atherosclerosis, in the past this has been attributed to their
      effects on blood cholesterol levels. Recent work, however, has shown that CMRs
      (chylomicron remnants), the lipoproteins which carry dietary lipids in the blood,
      potentially have a direct role in initiating atherogenesis by influencing
      vascular function. The Diet and Cardiovascular Health: Chylomicron Remnants and
      Their Emerging Roles in Vascular Dysfunction in Atherosclerosis Meeting focused
      attention on studies which have shown that CMRs influence vascular function via
      interactions with cells of the artery wall, including endothelial cells and
      macrophages, and also highlighted the part played by CMRs in the development of
      premature atherosclerosis in conditions such as the metabolic syndrome, which are
      an increasing cause of heart disease in developed countries.

PMID- 17511622
TI  - Comparison of the effects of dietary saturated, mono-unsaturated and
      polyunsaturated fatty acids on very-low-density lipoprotein secretion when
      delivered to hepatocytes in chylomicron remnant-like particles.
AB  - The effect of chylomicron remnant-like particles (CRLPs) enriched in saturated,
      mono-unsaturated or n-6 polyunsaturated fatty acids (derived from palm, olive or
      corn oil, respectively) on the secretion of VLDL (very-low-density lipoprotein)
      by rat hepatocytes in culture was investigated. CRLPs were incubated with
      cultured hepatocytes for 5 h. The medium was then removed and the secretion of
      cholesterol and triacylglycerol (TAG) into the whole medium during the following
      16 h was determined. After exposure of the cells to olive oil as compared with
      corn and palm oil CRLPs, secretion of TAG into the medium was decreased. The TAG
      content of the cells was also lower in experiments with olive oil as compared
      with corn oil CRLPs. The levels of apoB48 (apolipoprotein B48) found in the
      medium remained unchanged after the exposure of the cells to the different types
      of remnants. These findings indicate that the type of fat in the diet directly
      affects VLDL lipid secretion on delivery to the liver in chylomicron remnants.

PMID- 17511618
TI  - Gliogenesis and glial pathology in depression.
AB  - Recent research has changed the perception of glia from being no more than silent
      supportive cells of neurons to being dynamic partners participating in brain
      metabolism and communication between neurons. This discovery of new glial
      functions coincides with growing evidence of the involvement of glia in the
      neuropathology of mood disorders. Unanticipated reductions in the density and
      number of glial cells are reported in fronto-limbic brain regions in major
      depression and bipolar illness. Moreover, age-dependent decreases in the density
      of glial fibrillary acidic protein (GFAP) - immunoreactive astrocytes and levels
      of GFAP protein are observed in the prefrontal cortex of younger depressed
      subjects. Since astrocytes participate in the uptake, metabolism and recycling of
      glutamate, we hypothesize that an astrocytic deficit may account for the
      alterations in glutamate/GABA neurotransmission in depression. Reductions in the
      density and ultrastructure of oligodendrocytes are also detected in the
      prefrontal cortex and amygdala in depression. Pathological changes in
      oligodendrocytes may be relevant to the disruption of white matter tracts in mood
      disorders reported by diffusion tensor imaging. Factors such as stress, excess of
      glucocorticoids, altered gene expression of neurotrophic factors and glial
      transporters, and changes in extracellular levels of neurotransmitters released
      by neurons may modify glial cell number and affect the neurophysiology of
      depression. Therefore, we will explore the role of these events in the possible
      alteration of glial number and activity, and the capacity of glia as a promising
      new target for therapeutic medications. Finally, we will consider the temporal
      relationship between glial and neuronal cell pathology in depression.

PMID- 17511620
TI  - Co-planar 3,3',4,4',5-pentachlorinated biphenyl and non-co-planar 2,2',4,6,6'
      pentachlorinated biphenyl differentially induce recruitment of oestrogen receptor
      alpha to aryl hydrocarbon receptor target genes.
AB  - In the present study we examined the ability of 3,3',4,4',5-pentachlorinated
      biphenyl [PCB126 (polychlorinated biphenyl 126)], a prototypical AHR (aryl
      hydrocarbon receptor) agonist, and 2,2',4,6,6'-PCB (PCB104), which does not
      activate AHR, to induce the recruitment of ERalpha (oestrogen receptor alpha) to
      CYP1A1 (cytochrome P4501A1 gene) and CYP1B1 promoters in T-47D human breast
      cancer cells and other cell lines. PCB126 treatment strongly induced CYP1A1 and
      CYP1B1 mRNA expression that was unaffected by co-treatment with E2 (17beta
      oestradiol). PCB104 failed to induce changes in either CYP1A1 or CYP1B1
      expression levels. ChIP (chromatin immunoprecipitation) assays show that PCB126,
      but not PCB104, increased the promoter occupancy by ERalpha to CYP1A1 and CYP1B1
      promoters. Co-treatment with PCB126+E2 significantly enhanced the promoter
      occupancy of ERalpha at CYP1A1, whereas co-treatment with PCB126+4
      hydroxytamoxifen or ICI182,780 did not. Competitive binding studies revealed that
      neither PCB126 nor PCB104 bound to ERalpha. HEK-293 cells (human embryonic kidney
      293 cells) stably transfected with ERalpha showed significantly higher PCB126
      induced CYP1A1 expression compared with empty vector controls, whereas no
      increase was observed in cells stably transfected with ERalpha lacking its N
      terminal AF1 (activation function-1) domain (ERalphaDeltaAF1). Despite no
      increase in AHR-mediated gene expression, ChIP assays revealed that
      ERalphaDeltaAF1 was present at CYP1A1 and CYP1B1 promoters. HC11 mouse mammary
      cells stably expressing shRNA (small-hairpin RNA) against ERalpha showed an 8
      fold reduction in PCB126-dependent Cyp1a1 expression. Our results provide further
      evidence that AHR agonists induce ERalpha promoter occupancy at AHR target genes
      through indirect activation of ERalpha, and support a role for ERalpha in AHR
      transactivation.

PMID- 17511623
TI  - Chylomicron remnants: mediators of endothelial dysfunction?
AB  - Vascular disease is initiated by activation of the endothelium characterized by
      the predominance of pro-inflammatory and pro-coagulant changes in endothelial
      cells (ECs) referred to collectively as 'endothelial dysfunction'. There is
      increasing evidence that lipoproteins of dietary origin modulate EC function and
      the use of artificial chylomicron remnant-like particles (CRLPs) in vitro is now
      beginning to shed light on the molecular mechanisms through which these particles
      influence cell behaviour. CRLPs enriched in n-6 PUFAs (polyunsaturated fatty
      acids) influence the production of vasoactive mediators by ECs in a pro
      inflammatory manner. Thus CRLPs reduce the synthesis and release of nitric oxide
      and alter the balance of release of vasodilator versus vasoconstrictor
      eicosanoids. These changes are accompanied by induction of cyclo-oxygenase-2
      expression and activity as well as increased expression of adhesion molecules and
      the antioxidant defence enzyme haem oxygenase-1. CRLPs also activate a number of
      intracellular signalling pathways, including NF-kappaB (nuclear factor kappaB)
      and MAPKs (mitogen-activated protein kinases), which may be involved in mediating
      their effects on gene expression. The effects of CRLPs on EC behaviour can also
      be modulated by the type of fat/oxidation status of the particles. These findings
      support the hypothesis that lipoproteins of dietary origin directly regulate
      molecular events in the vascular wall.

PMID- 17511624
TI  - Modulation of the effects of chylomicron remnants on endothelial function by
      minor dietary lipid components.
AB  - There is emerging evidence that minor components from dietary oils can modulate
      or even improve events occurring in the development of atherosclerosis. One of
      the earliest events of the atherosclerotic process is endothelial dysfunction,
      which is an activation of the endothelium manifested by an increase in pro
      inflammatory molecules, such as cytokines and adhesion molecules. Chylomicron
      remnants, such as LDL (low-density lipoprotein), are considered to be pro
      atherogenic lipoproteins because they interact with endothelial cells and
      macrophages, increasing endothelial dysfunction mainly by the disturbance of the
      redox state in the cell. However, chylomicrons are, at the same time, the natural
      carriers of dietary lipids in plasma, which gives minor lipid components the
      opportunity to interact with the cells implicated in endothelial dysfunction and
      atherogenesis. Some of these components are known to exhibit antioxidant, anti
      inflammatory and anti-atherogenic effects in vitro, even forming part of
      triacylglycerol-rich lipoproteins, such as chylomicrons.

PMID- 17511625
TI  - Meal fatty acids and postprandial vascular reactivity.
AB  - With increasing recognition of the pivotal role of vascular dysfunction in the
      progression of atherosclerosis, the vasculature has emerged as an important
      target for dietary therapies. Recent studies have indicated that chronic fatty
      acid manipulation alters vascular reactivity, when measured after an overnight
      fast. However, individuals spend a large proportion of the day in the
      postprandial (non-fasted) state. Several studies have shown that high fat meals
      can impair endothelial function within 3-4 h, a time period often associated with
      peak postprandial lipaemia. Although the impact of meal fatty acids on the
      magnitude and duration of the postprandial lipaemic response has been extensively
      studied, very little is known about their impact on vascular reactivity after a
      meal.

PMID- 17511626
TI  - The induction of macrophage foam cell formation by chylomicron remnants.
AB  - The accumulation of foam cells in the artery wall causes fatty streaks, the first
      lesions in atherosclerosis. LDL (low-density lipoprotein) plays a major role in
      foam cell formation, although prior oxidation of the particles is required.
      Recent studies, however, have provided considerable evidence to indicate that
      CMRs (chylomicron remnants), which carry dietary lipids in the blood, induce foam
      cell formation without oxidation. We have shown that CMRs are taken up by
      macrophages and induce accumulation of both triacylglycerol and cholesterol, and
      that the rate of uptake and amount of lipid accumulated is influenced by the type
      of dietary fat in the particles. Furthermore, oxidation of CMRs, in striking
      contrast with LDL, inhibits, rather than enhances, their uptake and induction of
      lipid accumulation. In addition, the lipid accumulated after exposure of
      macrophages to CMRs is resistant to efflux, and this may be due to its
      sequestration in lysosomes. These findings demonstrate that CMRs induce pro
      atherogenic changes in macrophages, and that their effects may be modulated by
      dietary factors including oxidized fats, lipophilic antioxidants and the type of
      fat present.

PMID- 17511627
TI  - Mechanisms involved in chylomicron remnant lipid uptake by macrophages.
AB  - Although it is clear that chylomicron remnants are atherogenic, events leading to
      their internalization by macrophages are still debated. The lack of apoE
      (apolipoprotein E) in CRLPs (chylomicron remnant-like particles) reduces
      macrophage TAG (triacylglycerol) content by approx. 50%, suggesting that, as well
      as apoE-mediated endocytic uptake, apoE receptor-independent mechanisms are
      involved in the induction of foam cells by chylomicron remnants. Evaluation of
      the radioactivity associated with macrophages after incubation with CRLPs
      containing radiolabelled lipids suggests that the TAG and cholesterol carried by
      the particles have different kinetics of internalization. In addition, inhibition
      based experiments indicate that cholesteryl ester-selective uptake and the
      extracellular lipoprotein lipase hydrolysis of TAG contribute to cholesterol and
      TAG accumulation respectively. Thus plasma TAG and cholesterol carried by remnant
      particles have to be considered two independent and non-interchangeable risk
      factors for athero-related diseases. In addition, the interaction between CRLPs
      and macrophages is modulated by dietary oxidized lipids and other lipophilic
      components. The presence of oxidized lipids, such as 7beta-hydroxycholesterol and
      7-oxocholesterol, the major cholesterol oxidation products found in
      atherosclerotic lesions, in CRLPs interferes with the mechanisms of their
      internalization, but does not cause quantitative changes of accumulated lipids,
      while the presence of the plant carotenoid, lycopene, or the antioxidant drug,
      probucol, enhances lipid accumulation in macrophages by increasing the rate of
      uptake of the particles and raising the intracellular synthesis of TAG. In
      conclusion, several mechanisms contribute to the macrophage uptake of
      postprandial lipoproteins, however, little is known of the balance and modulation
      between the different pathways.

PMID- 17511628
TI  - Dietary fats induce human monocyte activation in vitro.
AB  - In early atherosclerosis the frequency of activated monocytes in the peripheral
      circulation is amplified, and migration of monocytes into the walls of the aorta
      and large arteries is increased, due partly to de novo expression or activation
      of monocyte adhesion molecules. Although there is increasing evidence that CMRs
      (chylomicron remnants) are strongly atherogenic, the outcomes of interactions
      between blood monocytes and circulating CMRs are not known. Here, we have studied
      the effects of CRLPs (CMR-like particles) on THP-1 human monocyte oxidative
      burst. The particles induced a significant increase in reactive oxygen species
      within 1 h, which persisted for 24 h. We suggest that monocyte-CMR interactions
      may be important in early atherosclerosis when many activated monocytes are found
      in susceptible areas of the artery wall.

PMID- 17511629
TI  - Postprandial inflammation and endothelial dysfuction.
AB  - Postprandial hyperlipidaemia is a common metabolic disturbance in
      atherosclerosis. During the postprandial phase, chylomicrons and their remnants
      can penetrate the intact endothelium and cause foam cell formation. These
      particles are highly atherogenic after modification. People in the Western world
      are non-fasting for most of the day, which consequently leads to a continuous
      challenge of the endothelium by atherogenic lipoproteins and their remnants.
      Furthermore, atherosclerosis is considered a low-grade chronic inflammatory
      disease. Many studies have shown that the process of atherogenesis in part starts
      with the interaction between the activated leucocytes and activated endothelium.
      Postprandial lipoproteins can activate leucocytes in the blood and up-regulate
      the expression of leucocyte adhesion molecules on the endothelium, facilitating
      adhesion and migration of inflammatory cells into the subendothelial space.
      Another inflammatory process associated with postprandial lipaemia is the
      activation of the complement system. Its central component C3 has been associated
      with obesity, coronary sclerosis, the metabolic syndrome and fasting and
      postprandial TAGs (triacylglycerols). Moreover, chylomicrons are the strongest
      stimulators of adipocyte C3 production via activation of the alternative
      complement cascade. A postprandial C3 increment has been shown in healthy
      subjects and in patients with CAD (coronary artery disease) and with FCHL
      (familial combined hyperlipidaemia). Postprandial lipaemia has been related to
      TAG and free fatty acid metabolism. All of these mechanisms provide an
      alternative explanation for the atherogenicity of the postprandial period.

PMID- 17511630
TI  - Influence of minor components of olive oils on the composition and size of TRLs
      and on macrophage receptors involved in foam cell formation.
AB  - Metabolic and epidemiologic studies support the idea that the type of dietary fat
      is more important than the total amount of fat with respect to the development of
      atherosclerosis and the risk of cardiovascular heart disease. Dietary fat is
      carried in CMs (chylomicrons), which can be taken up by macrophages without need
      of further oxidation, leading to the formation of foam cells and initiating or
      aggravating the atherogenic process. Evidence from different studies has shown
      that dietary fat can influence the composition and size of TRLs (triacylglycerol
      rich lipoproteins), which might modulate their atherogenicity to a certain
      extent. In particular, experiments in vitro have shown the anti-atherogenic
      effects of minor components from olive oil when forming part of TRL, as these
      particles give minor lipid components the opportunity to interact with the cells
      implicated in endothelial dysfunction and atherogenesis. However, the exact
      mechanisms mediating CM uptake by macrophages still remain unclear. Thus further
      studies are needed to understand how the modifications of TRL composition caused
      by dietary fats could modulate the expression of macrophage receptors and foam
      cell formation, or even improve the atherogenic risk of these particles.

PMID- 17511631
TI  - Removal of triacylglycerols from chylomicrons and VLDL by capillary beds: the
      basis of lipoprotein remnant formation.
AB  - The triacylglycerol content of chylomicrons and VLDL (very-low-density
      lipoprotein) compete for the same lipolytic pathway in the capillary beds.
      Although chylomicron triacylglycerols appear to be the favoured substrate for
      lipoprotein lipase, VLDL particles compete in numbers. Methods to quantify the
      specific triacylglycerol removal from VLDL and chylomicrons may involve
      endogenous labelling of the triacylglycerol substrate with stable isotopes in
      combination with arteriovenous blood sampling in humans. Arteriovenous
      quantification of remnant lipoproteins suggests that adipose tissue with its high
      lipoprotein lipase activity is a principal site for generation of remnant
      lipoproteins. Under circumstances of reduced efficiency in the removal of
      triacylglycerols from lipoproteins, there is accumulation of remnant
      lipoproteins, which are potentially atherogenic.

PMID- 17511632
TI  - Chylomicron and apoB48 metabolism in the JCR:LA corpulent rat, a model for the
      metabolic syndrome.
AB  - Postprandial (PP) lipaemia is a significant contributor to the development of
      dyslipidaemia and cardiovascular disease (CVD). It is also evident that PP
      lipaemia is prevalent during conditions of obesity and insulin resistance (IR)
      and may contribute to increased progression of CVD. Our group has assessed the
      potential of the obese JCR:LA-cp rat as a model of PP lipaemia in order to
      explore CM (chylomicron) metabolism during the onset and development of IR in the
      metabolic syndrome. Studies confirm that both fasting plasma and PP apoB48
      (apolipoprotein B48) area under the curve are significantly elevated in the obese
      JCR:LA-cp phenotype as compared with lean controls. Mechanistic studies have also
      shown that the concentration of lymphatic CM apoB48 and CM size are significantly
      increased in this model. Furthermore, PP dyslipidaemia in the obese rat can be
      improved acutely with supplementation of n-3 polyunsaturated fatty acids. Using a
      different approach, we have subsequently hypothesized that the vascular
      remodelling that accompanies IR may explain accelerated entrapment of apoB48
      containing particles. Small leucine-rich proteoglycans (including biglycan and
      decorin) have been observed to co-localize with apoB in human tissue. However,
      the potential impact of IR on vascular remodelling, particularly in the presence
      of obesity, remains unclear. Preliminary observations from the JCR:LA-cp model
      indicate that biglycan protein core content increases with age and is exacerbated
      by IR, suggestive of pro-atherogenic remodelling. The focus of this review is to
      contribute to the perspective of PP lipaemia in CVD risk associated with the
      metabolic syndrome through the use of animal models.

PMID- 17511633
TI  - Measurement of endogenous and exogenous triacylglycerol kinetics in the fed and
      fasted states.
AB  - Emerging evidence has shown that an abnormal postprandial accumulation of dietary
      fat is atherogenic. However, there is a lack of data describing the mechanisms
      for accumulation of triacylglycerol (TAG) in the postprandial period. There is
      therefore a need to establish a specific measure of the kinetics of endogenous
      and exogenous TAG in the postprandial period.

PMID- 17511635
TI  - Peptide alpha-helices for synthetic nanostructures.
AB  - Supramolecular structures arising from a broad range of chemical archetypes are
      of great technological promise. Defining such structures at the nanoscale is
      crucial to access principally new types of functional materials for applications
      in bionanotechnology. In this vein, biomolecular self-assembly has emerged as an
      efficient approach for building synthetic nanostructures from the bottom up. The
      approach predominantly employs the spontaneous folding of biopolymers to
      monodisperse three-dimensional shapes that assemble into hierarchically defined
      mesoscale composites. An immediate interest here is the extraction of reliable
      rules that link the chemistry of biopolymers to the mechanisms of their assembly.
      Once established these can be further harnessed in designing supramolecular
      objects de novo. Different biopolymer classes compile a rich repertoire of
      assembly motifs to facilitate the synthesis of otherwise inaccessible
      nanostructures. Among those are peptide alpha-helices, ubiquitous folding
      elements of natural protein assemblies. These are particularly appealing
      candidates for prescriptive supramolecular engineering, as their well-established
      and conservative design rules give unmatched predictability and rationale. Recent
      developments of self-assembling systems based on helical peptides, including
      fibrous systems, nanoscale linkers and reactors will be highlighted herein.

PMID- 17511634
TI  - Apolipoprotein B48: a novel marker of metabolic risk in overweight children?
AB  - Clinical studies in adults indicate there is a positive and significant
      association between insulin resistance, dyslipidaemia, fasting intestinally
      derived lipoproteins [via apoB48 (apolipoprotein B48)] and visceral fat. All of
      these factors contribute to increased risk of CVD (cardiovascular disease). Since
      little is known about postprandial dyslipidaemia in overweight children, we
      sought to compare fasting levels of apoB48 with the HOMA-IR (homoeostasis model
      assessment of insulin resistance) score, classic lipid profile and VAT (visceral
      adipose tissue). Pre-pubertal, overweight boys and girls were recruited from the
      wider-Edmonton area (Alberta). Body composition was determined using both dual
      energy X-ray absorptiometry and MRI (magnetic resonance imaging). Fasting apoB48
      was quantified in plasma using an adapted SDS/PAGE immunoblotting technique, and
      insulin, glucose, TC (total cholesterol), TAG (triacylglycerol), LDL (low-density
      lipoprotein) and HDL (high-density lipoprotein) were determined by calorimetric
      assay. In this overweight sample, we observed elevated fasting apoB48
      concentrations, greater than the normal adult range. In addition, apoB48 was
      significantly related to HOMA-IR and TAG levels. Although apoB48 was positively
      correlated with TC and LDL and negatively associated with HDL, these
      relationships did not achieve significance. Our ongoing MRI analysis reveals a
      positive relationship between apoB48 and VAT volume. To our knowledge, this is
      the first study to report apoB48 concentrations in overweight pre-pubertal
      children. Thus this article will provide a brief rationale for our study and its
      methodology.

PMID- 17511636
TI  - Attachment of proteins to molecular printboards through orthogonal multivalent
      linkers.
AB  - The attachment of proteins to a surface in such a way that the protein remains
      functional, is a key issue in many biotechnological processes. Here, we describe
      the controlled attachment with respect to kinetics, thermodynamics and
      orientation of SAv (streptavidin) through an orthogonal linker to beta
      cyclodextrin selfassembled monolayers. Both a univalent and a bivalent linker are
      used for this process. The immobilization strategy with the bivalent linker
      allows the stepwise adsorption of SAv on to the surface, allowing
      heterofunctionalization of SAv and thus the build-up of more complex
      bionanostructures at the surface.

PMID- 17511637
TI  - PDNA as building blocks for membrane-guided self-assemblies.
AB  - Different semi-synthetic PDNAs (protein-DNA complexes), which encompass a protein
      core engineered from the cytochrome b(5) scaffold, an embedded tuneable redox
      cofactor, a synthetic linker and a large oligonucleotide, were designed,
      synthesized and purified to homogeneity. These building blocks can be reversibly
      attached to Ni-DOGS [1,2-dioleoyl-sn-glycero-3-[N(5-amino-1
      carboxypentyl)iminodiacetic acid]succinyl]-doped supported membranes through a
      metal chelate bridge with the protein part and be polymerized in a fully
      controllable manner using a solid-phase synthesis strategy and a stepwise
      addition of suitable complementary oligonucleotides. The resulting structures
      could recreate a large range of regular distribution of patterned redox and
      absorbing centres separated by fully tuneable distances and geometry. Kinetic
      parameters for the self-assembly of building blocks were determined using SPRI
      (surface plasmon resonance imagery). Structures of resulting nano-objects were
      characterized using gel electrophoresis and single molecule approaches following
      decoration of assemblies with quantum dots.

PMID- 17511638
TI  - Using membrane stress to our advantage.
AB  - The nature of the bilayer motif coupled with the ability of lipids and proteins
      to diffuse freely through this structure is crucial to the viability of cells and
      their ability to compartmentalize domains contained therein. It seems surprising
      to find then that biological as well as model membranes exist in a dynamic state
      of mechanical stress. The stresses within such membranes are surprisingly large,
      typically reaching up to 50 atm (1 atm=101.325 kPa) at the core of the membrane
      and vary as a function of depth. The uneven distribution of lateral pressures
      within monolayer leaflets causes them to bend away from or towards the water
      interface. This can result in the formation of complex, self-assembled
      mesophases, many of which occur in vivo. Our knowledge of the principles
      underlying membrane mechanics has reached the point where we are now able to
      manipulate them and create nano-structures with reasonable predictability. In
      addition, they can be used both to explain and control the partitioning of
      amphipathic proteins on to membranes. The dependence of the dynamics of membrane
      bound proteins and the chemical reactivity of amphipathic drug molecules on
      membrane stresses suggests that Nature itself takes advantage of this.
      Understanding and manipulating these internal forces will be a key element in
      creating self-assembled, biocompatible, nanoscale cell-like systems.

PMID- 17511639
TI  - Design and chance in the self-assembly of macromolecules.
AB  - The principles of self-assembly are described for naturally occurring
      macromolecules and for complex assemblies formed from simple synthetic
      constituents. Many biological molecules owe their function and specificity to
      their three-dimensional folds, and, in many cases, these folds are specified
      entirely by the sequence of the constituent amino acids or nucleic acids, and
      without the requirement for additional machinery to guide the formation of the
      structure. Thus sequence may often be sufficient to guide the assembly process,
      starting from denatured components having little or no folds, to the completion
      state with the stable, equilibrium fold that encompasses functional activity.
      Self-assembly of homopolymeric structures does not necessarily preserve symmetry,
      and some polymeric assemblies are organized so that their chemically identical
      subunits pack stably in geometrically non-equivalent ways. Self-assembly can also
      involve scaffolds that lack structure, as seen in the multi-enzyme assembly, the
      degradosome. The stable self-assembly of lipids into dynamic membraneous sheets
      is also described, and an example is shown in which a synthetic detergent can
      assemble into membrane layers.

PMID- 17511640
TI  - Self-assembly in the carboxysome: a viral capsid-like protein shell in bacterial
      cells.
AB  - Many proteins self-assemble to form large supramolecular complexes. Numerous
      examples of these structures have been characterized, ranging from spherical
      viruses to tubular protein assemblies. Some new kinds of supramolecular
      structures are just coming to light, while it is likely there are others that
      have not yet been discovered. The carboxysome is a subcellular structure that has
      been known for more than 40 years, but whose structural and functional details
      are just now emerging. This giant polyhedral body is constructed as a closed
      shell assembled from several thousand protein subunits. Within this protein
      shell, the carboxysome encapsulates the CO(2)-fixing enzymes, Rubisco (ribulose
      1,5-bisphosphate carboxylase/oxygenase) and carbonic anhydrase; this arrangement
      enhances the efficiency of cellular CO(2) fixation. The carboxysome is present in
      many photosynthetic and chemoautotrophic bacteria, and so plays an important role
      in the global carbon cycle. It also serves as the prototypical member of what
      appears to be a large class of primitive protein-based organelles in bacteria. A
      series of crystal structures is beginning to reveal the secrets of how the
      carboxysome is assembled and how it enhances the efficiency of CO(2) fixation.
      Some of the assembly principles revealed in the carboxysome are reminiscent of
      those seen in icosahedral viral capsids. In addition, the shell appears to be
      perforated by pores for metabolite transport into and out of the carboxysome,
      suggesting comparisons to the pores through oligomeric transmembrane proteins,
      which serve to transport small molecules across the membrane bilayers of cells
      and eukaryotic organelles.

PMID- 17511641
TI  - Bio-based approaches to inorganic material synthesis.
AB  - Nature is an exquisite designer of inorganic materials using biomolecules as
      templates. Diatoms create intricate silica wall structures with fine features
      using the protein family of silaffins as templates. Marine sponges create silica
      spicules also using proteins, termed silicateins. In recent years, our group and
      others have used biomolecules as templates for the deposition of inorganic
      materials. In contrast with the traditional materials science approach, which
      requires high heat, extreme pH and non-aqueous solutions, the bio-based
      approaches allow the reactions to proceed usually at near ambient conditions.
      Additionally, the biological templates allow for the control of the inorganic
      nanoparticle morphology. The use of peptides and biomolecules for templating and
      assembling inorganics will be discussed here.

PMID- 17511642
TI  - Putting the fizz into chemistry: applications of supercritical carbon dioxide in
      tissue engineering, drug delivery and synthesis of novel block copolymers.
AB  - This paper describes the recent progress at Nottingham towards the exploitation
      of the unique properties of scCO(2) (supercritical carbon dioxide) for the
      preparation of polymeric scaffolds for tissue engineering applications and new
      devices for controlled drug delivery, as well as the synthesis of novel block
      copolymers by the combination of eROP (enzymatic ring opening polymerization) and
      controlled polymerization methods for the potential use as drug carriers.

PMID- 17511643
TI  - Self-assembling layers created by membrane proteins on gold.
AB  - Membrane systems are based on several types of organization. First, amphiphilic
      lipids are able to create monolayer and bilayer structures which may be flat,
      vesicular or micellar. Into these structures membrane proteins can be inserted
      which use the membrane to provide signals for lateral and orientational
      organization. Furthermore, the proteins are the product of highly specific self
      assembly otherwise known as folding, which mostly places individual atoms at
      precise places in three dimensions. These structures all have dimensions in the
      nanoscale, except for the size of membrane planes which may extend for
      millimetres in large liposomes or centimetres on planar surfaces such as
      monolayers at the air/water interface. Membrane systems can be assembled on to
      surfaces to create supported bilayers and these have uses in biosensors and in
      electrical measurements using modified ion channels. The supported systems also
      allow for measurements using spectroscopy, surface plasmon resonance and atomic
      force microscopy. By combining the roles of lipids and proteins, highly ordered
      and specific structures can be self-assembled in aqueous solution at the
      nanoscale.

PMID- 17511644
TI  - Health effects of nanomaterials.
AB  - With the rapid growth of nanotechnology and future bulk manufacture of
      nanomaterials comes the need to determine, understand and counteract any adverse
      health effects of these materials that may occur during manufacture, during use,
      or accidentally. Nanotechnology is expanding rapidly and will affect many aspects
      of everyday life; there are already hundreds of products that utilize
      nanoparticles. Paradoxically, the unique properties that are being exploited
      (e.g. high surface reactivity and ability to cross cell membranes) might have
      negative health impacts. The rapid progress in development and use of
      nanomaterials is not yet matched by toxicological investigations. Epidemiological
      studies implicate the ultrafine (nano-sized) fraction of particulate air
      pollution in the exacerbation of cardiorespiratory disease and increased
      morbidity. Experimental animal studies suggest that the increased concentration
      of nanoparticles and higher reactive surface area per unit mass, alongside unique
      chemistry and functionality, is important in the acute inflammatory and chronic
      response. Some animal models have shown that nanoparticles which are deposited in
      one organ (e.g. lung and gut) may access the vasculature and target other organs
      (e.g. brain and liver). The exact relationship between the physicochemistry of a
      nanoparticle, its cellular reactivity, and its biological and systemic
      consequences cannot be predicted. It is important to understand such
      relationships to enjoy the benefits of nanotechnology without being exposed to
      the hazards.

PMID- 17511645
TI  - Synthetic de novo designed polypeptides for control of nanoparticle assembly and
      biosensing.
AB  - This contribution describes how de novo designed synthetic helix-loop-helix
      polypeptides are utilized to control the assembly of gold nanoparticles and as
      scaffolds for biosensing. The synthetic polypeptides are designed to fold into a
      four-helix bundle upon dimerization. When immobilized on gold nanoparticles,
      dimerization and folding occur between peptides on neighbouring particles as an
      effect of particle aggregation and the folded polypeptides are rigid enough to
      keep the particles separated at a distance corresponding to the size of the four
      helix bundle. Moreover, peptide dimerization offers a convenient route to
      assemble nanoparticles into hybrid multilayers on planar substrates. The drastic
      change in the resonance conditions of the localized nanoparticle surface plasmon
      upon particle aggregation is shown to be useful for optical detection of
      biomolecular interactions.

PMID- 17511646
TI  - Three-dimensional cell culture of chondrocytes on modified di-phenylalanine
      scaffolds.
AB  - The design of self-assembled peptide-based structures for three-dimensional cell
      culture and tissue repair has been a key objective in biomaterials science for
      decades. In search of the simplest possible peptide system that can self
      assemble, we discovered that combinations of di-peptides that are modified with
      aromatic stacking ligands could form nanometre-sized fibres when exposed to
      physiological conditions. For example, we demonstrated that a number of Fmoc
      (fluoren-9-ylmethyloxycarbonyl) modified di- and tri-peptides form highly ordered
      hydrogels via hydrogen-bonding and pi-pi interactions from the fluorenyl rings.
      These highly hydrated gels allowed for cell proliferation of chondrocytes in
      three dimensions [Jayawarna, Ali, Jowitt, Miller, Saiani, Gough and Ulijn (2006)
      Adv. Mater. 18, 611-614]. We demonstrated that fibrous architecture and physical
      properties of the resulting materials were dictated by the nature of the amino
      acid building blocks. Here, we report the self-assembly process of three di
      phenylalanine analogues, Fmoc-Phe-Phe-OH, Nap (naphthalene)-Phe-Phe-OH and Cbz
      (benzyloxycarbonyl)-Phe-Phe-OH, to compare and contrast the self-assembly
      properties and cell culture conditions attributable to their protecting group
      difference. Fibre morphology analysis of the three structures using cryo-SEM
      (scanning electron microscopy) and TEM (transmission electron microscopy)
      suggested fibrous structures with dramatically varying fibril dimensions,
      depending on the aromatic ligand used. CD and FTIR (Fourier-transform IR) data
      confirmed beta-sheet arrangements in all three samples in the gel state. The
      ability of these three new hydrogels to support cell proliferation of
      chondrocytes was confirmed for all three materials.

PMID- 17511647
TI  - The delivery of PEBBLE nanosensors to measure the intracellular environment.
AB  - Cellular introduction of PEBBLEs (photonic explorers for bioanalysis with
      biologically localized embedding) has been investigated by a wide variety of
      methods in a range of cell types. These methods include surface functionalization
      with CPPs (cell-penetrating peptides), pinocytosis, commercial lipid transfection
      agents, cytochalasin D, picoinjection, and Gene gun bombardment. This paper will
      overview several of the most popular methods used for the introduction of PEBBLE
      nanosensors to the cellular environment and discuss the efficacy of the
      techniques.

PMID- 17511648
TI  - Raman microspectroscopy for non-invasive biochemical analysis of single cells.
AB  - Recent developments in biomedical vibrational spectroscopy now permit the non
      invasive imaging of cells and tissues within both the laboratory and clinical
      settings. The rapid nature and diagnostic potential of both Raman and FTIR
      (Fourier-transform IR) spectroscopy have resulted in their widespread application
      to a number of biological fields including fundamental cell biology, medical
      imaging, tissue engineering and pharmacology. In particular, Raman
      microspectroscopy shows tremendous promise for the analysis of biological
      processes within living cells, such as cell cycle dynamics, cell differentiation
      and cell death. Unlike conventional biological assays, laser-based Raman
      spectroscopy enables rapid and non-invasive biochemical analysis of cells in the
      absence of fixatives or labels. The low Raman signal of cell culture buffer/media
      permits the rapid monitoring of living cells growing under standard cell culture
      conditions. The Raman spectrum of a cell is a biochemical 'fingerprint',
      containing molecular-level information about all biopolymers contained within the
      cell. The high information content of Raman spectra can be used to characterize
      the distribution of multiple cellular components, and to study the dynamics of
      subcellular reactions, with excellent spatial resolution. This review highlights
      recent developments in Raman microspectroscopy, with a focus on non-invasive
      biochemical analysis of single living cells.

PMID- 17511649
TI  - An alternative strategy for inhibiting multidrug-resistant mutants of the dimeric
      HIV-1 protease by targeting the subunit interface.
AB  - Mutations that occur in response to the HIV-1 protease inhibitors are responsible
      for the development of multidrug cross-resistance to these antiproteases in AIDS
      treatment. One alternative to inhibiting the active site of HIV-1 protease is to
      target the dimer interface of the homodimeric enzyme at the antiparallel beta
      sheet formed by the interdigitation of the C- and N-ends of each monomer. This
      region is highly conserved and is responsible for approx. 75% of the dimer
      stabilization energy. The strategies that have been used to design small
      molecules to target the interface antiparallel beta-sheet have produced
      lipopeptides, guanidinium derivatives and peptides (or peptidomimetics) cross
      linked with spacers. The mechanism of inhibition was determined using a
      combination of kinetic and biophysical methods. These dimerization inhibitors
      proved equally active in vitro against both wild-type and mutated proteases. They
      are therefore promising alternatives to active-site-directed inhibitors in AIDS
      therapy. Disruption of protein-protein interactions by small molecules is a new
      way to obtain potentially therapeutic molecules.

PMID- 17511650
TI  - The quest for Factor VIIa exosite inhibitors.
AB  - Coagulation proteases are involved in a highly orchestrated proteolytic cascade
      which is essential for haemostasis and blood clotting. In particular, the
      initiator of the coagulation cascade, Factor VIIa, binds to its cofactor, tissue
      factor, and its substrate, Factor X, via exosite interactions to form a ternary
      catalytic complex named extrinsic Xase. These exosite interactions have also been
      shown to allosterically induce the active conformation of the catalytic site of
      Factor VIIa. We have developed a direct continuous fluorescence polarization
      based extrinsic Xase assay, which has been used to screen in excess of 1 million
      structurally diverse low-molecular-mass compounds as a potential starting point
      for the development of anticoagulants. The primary screen hits were categorized
      with deconvolution assays into either active-site or exosite inhibitors. The
      latter category of hits displayed both competitive and uncompetitive modalities
      of inhibition with respect to Factor X activation. An uncompetitive mechanism of
      action is of particular interest as it offers a hypothetical inhibitory advantage
      in the context of inhibiting a proteolytic cascade such as the blood coagulation
      pathway.

PMID- 17511651
TI  - The emerging role of serine proteases in apoptosis.
AB  - Unregulated apoptosis can be due to a disruption in the balance and control of
      both intra- and inter-cellular proteolytic activities leading to various disease
      states. Many proteases involved in apoptotic processes are yet to be identified;
      however, several are already well characterized. Caspases traditionally held the
      predominant role as prime mediators of execution. However, latterly, evidence has
      accumulated that non-caspases, including calpains, cathepsins, granzymes and the
      proteasome have roles in mediating and promoting cell death. Increasingly,
      research is implicating serine proteases within apoptotic processing,
      particularly in the generation of nuclear events such as condensation,
      fragmentation and DNA degradation observed in late-stage apoptosis. Serine
      proteases therefore are emerging as providing additional or alternative
      therapeutic targets.

PMID- 17511652
TI  - New opportunities for protease ligand-binding site comparisons using SitesBase.
AB  - The rapid expansion of structural information for protein ligand-binding sites is
      potentially an important source of information in structure-based drug design and
      in understanding ligand cross-reactivity and toxicity. We have developed
      SitesBase, a comprehensive database of ligand-binding sites extracted
      automatically from the Macromolecular Structure Database. SitesBase is an easily
      accessible database which is simple to use and holds pre-calculated information
      about structural similarities between known ligand-binding sites. These
      similarities are presented to the wider community enabling binding-site
      comparisons for therapeutically interesting protein families, such as the
      proteases and for new proteins to enable the discovery of interesting new
      structure-function relationships. The database is available from
      http://www.modelling.leeds.ac.uk/sb/.

PMID- 17511653
TI  - 13C- and 1H-NMR studies of oxyanion and tetrahedral intermediate stabilization by
      the serine proteinases: optimizing inhibitor warhead specificity and potency by
      studying the inhibition of the serine proteinases by peptide-derived
      chloromethane and glyoxal inhibitors.
AB  - Catalysis by the serine proteinases proceeds via a tetrahedral intermediate whose
      oxyanion is stabilized by hydrogen-bonding in the oxyanion hole. There have been
      extensive (13)C-NMR studies of oxyanion and tetrahedral intermediate
      stabilization in trypsin, subtilisin and chymotrypsin using substrate-derived
      chloromethane inhibitors. One of the limitations of these inhibitors is that they
      irreversibly alkylate the active-site histidine residue which results in the
      oxyanion not being in the optimal position in the oxyanion hole. Substrate
      derived glyoxal inhibitors are reversible inhibitors which, if they form
      tetrahedral adducts in the same way as substrates form tetrahedral intermediates,
      will overcome this limitation. Therefore we have synthesized (13)C-enriched
      substrate-derived glyoxal inhibitors which have allowed us to use (13)C-NMR and
      (1)H-NMR to determine how they interact with proteinases. It is hoped that these
      studies will help in the design of specific and highly potent warheads for serine
      proteinase inhibitors.

PMID- 17511654
TI  - A copper-binding site in the cytoplasmic domain of BACE1 identifies a possible
      link to metal homoeostasis and oxidative stress in Alzheimer's disease.
AB  - The amyloidogenic processing pathway of the APP (amyloid precursor protein)
      generates Abeta (amyloid beta-peptide), the major constituent in Alzheimer's
      disease senile plaques. This processing is catalysed by two unusual membrane
      localized aspartic proteinases, beta-secretase [BACE1 (beta-site APP-cleaving
      enzyme 1)] and the gamma-secretase complex. There is a clear link between APP
      processing and copper homoeostasis in the brain. APP binds copper and zinc in the
      extracellular domain and Abeta also binds copper, zinc and iron. We have found
      that a 24-residue peptide corresponding to the C-terminal domain of BACE1 binds a
      single copper(I) atom with high affinity through cysteine residues. We also
      observed that the cytoplasmic domain of BACE1 interacts with CCS, the dedicated
      copper chaperone for SOD1 (superoxide dismutase 1). Overproduction of BACE1
      reduces SOD1 activity in cells. Consequently, SOD1 activity, cytosolic copper and
      ectodomain cleavage of APP are linked through BACE1.

PMID- 17511655
TI  - The proteins BACE1 and BACE2 and beta-secretase activity in normal and
      Alzheimer's disease brain.
AB  - The insidious progression of AD (Alzheimer's disease) is believed to be linked
      closely to the production, accumulation and aggregation of the approximately 4.5
      kDa protein fragment called Abeta (amyloid beta-peptide). Abeta is produced by
      sequential cleavage of the amyloid precursor protein by two enzymes referred to
      as beta- and gamma-secretase. beta-Secretase is of central importance, as it
      catalyses the rate-limiting step in the production of Abeta and was identified 7
      years ago as BACE1 (beta-site APP-cleaving enzyme 1). Soon afterwards, its
      homologue BACE2 was discovered, and both proteins represent a new subclass of the
      aspartyl protease family. Studies examining the regulation and function of beta
      secretase in the normal and AD brain are central to the understanding of
      excessive production of Abeta in AD, and in targeting and normalizing this beta
      secretase process if it has gone awry in the disease. Several reports indicate
      this, showing increased beta-secretase activity in AD, with recent findings by
      our group showing changes in beta-secretase enzyme kinetics in AD brain caused by
      an increased V(max). This article gives a brief review of studies which have
      examined BACE1 protein levels and beta-secretase activity in control and AD
      brain, considering further the expression of BACE2 in the human brain.

PMID- 17511656
TI  - Regulation of the lipidation of beta-secretase by statins.
AB  - Statins inhibit the dimerization of beta-secretase [BACE (beta-site amyloid
      precursor protein-cleaving enzyme)] by inhibiting the lipidation of BACE and
      associated proteins. Our studies have demonstrated a clearly defined temporal
      sequence for these reactions in the assembly of the BACE complex, which may
      provide targets for the treatment of Alzheimer's disease.

PMID- 17511657
TI  - Roles and regulation of membrane-associated serine proteases.
AB  - Pericellular proteolytic activity affects many aspects of cellular behaviour, via
      mechanisms involving processing of the extracellular matrix, growth factors and
      receptors. The serine proteases have exquisitely sensitive regulatory mechanisms
      in this setting, involving both receptor-bound and transmembrane proteases.
      Receptor-bound proteases are exemplified by the uPA (urokinase plasminogen
      activator)/uPAR (uPAR receptor) plasminogen activation system. The mechanisms
      initiating the activity of this proteolytic system on the cell surface, a
      critical regulatory point, are poorly understood. We have found that the
      expression of the TTSP (type II transmembrane serine protease) matriptase is
      highly regulated in leucocytes, and correlates with the presence of active uPA on
      their surface. Using siRNA (small interfering RNA), we have demonstrated that
      matriptase specifically activates uPAR-associated pro-uPA. The uPA/uPAR system
      has been implicated in the activation of the plasminogen-related growth factor
      HGF (hepatocyte growth factor). However, we find no evidence for this, but
      instead that HGF can be activated by both matriptase and the related TTSP hepsin
      in purified systems. Hepsin is of particular interest, as the proteolytic
      cleavage sequence of HGF is an 'ideal substrate' for hepsin and membrane
      associated hepsin activates HGF with high efficiency. Both of these TTSPs can be
      activated autocatalytically at the cell surface, an unusual mechanism among the
      serine proteases. Therefore these TTSPs have the capacity to be true upstream
      initiators of proteolytic activity with subsequent downstream effects on cell
      behaviour.

PMID- 17511658
TI  - Neuropeptidomics: expanding proteomics downwards.
AB  - Biological function is mainly carried out by a dynamic population of proteins and
      peptides which may be used as markers for disease diagnosis, prognosis and as a
      guide for effective treatment. The study of proteins is called proteomics and it
      is generally performed by two-dimensional gel electrophoresis and mass
      spectrometric methods. However, gel-based proteomics is methodologically
      restricted from the low mass region, which includes important endogenous
      peptides. The study of endogenous peptides, peptidomics, is complicated by
      protein fragments produced post-mortem during conventional sample handling.
      Nanoflow liquid chromatography and MS, together with improved methods for sample
      preparation, have been used to semi-quantitatively monitor endogenous peptides in
      brain tissue. When rapidly heat-denatured brain tissue was analysed, these
      methods enabled simultaneous detection of hundreds of peptides and the
      identification of several endogenous peptides not previously described in the
      literature. In an application of the MPTP (1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine) model for Parkinson's disease, the expression of the small
      protein PEP-19 was compared with controls. The levels were found to be
      significantly decreased in the striatum of MPTP-treated animals.

PMID- 17511659
TI  - Structural analysis of foot-and-mouth disease virus 3C protease: a viable target
      for antiviral drugs?
AB  - Foot-and-mouth disease virus causes a major global agricultural problem that is
      difficult to control with existing vaccines. Structural analyses of the viral 3C
      protease not only have provided fresh insights into the catalytic mechanism of an
      unusual class of chymotrypsin-like cysteine proteases, but also are generating
      valuable information to drive the quest for effective antiviral therapies.

PMID- 17511660
TI  - Exploiting new genome data and Internet resources for the phylogenetic analysis
      of proteases, substrates and inhibitors.
AB  - Multiple alignments and phylogenetic tree constructions are established
      techniques for examining the evolutionary history of protease sequences in
      organisms such as humans, mice, fruitflies, nematode worms and yeast. They also
      facilitate the mapping of those conserved positions that are important for
      structure and catalytic function. However, the continued increase in completed or
      draft genomes offers new opportunities for examining protease evolution across a
      broader (e.g. more mammals) and deeper (e.g. more invertebrates) phylogenetic
      range. In addition, the improving annotation not only of proteases, but also of
      their substrates, interaction partners in proteolytic complexes and endogenous
      inhibitor proteins now means that aspects of co-evolution can be addressed. The
      increasing phylogenetic coverage is also important for resolving orthology issues
      that arise from protease gene duplication or loss in different lineages. Selected
      sequences will be used to exemplify the utility of Internet resources and present
      results for these types of analysis.

PMID- 17511661
TI  - The testis as a conduit for genomic plasticity: an advanced interdisciplinary
      workshop.
AB  - The premise for this unusual amalgamation of reproductive biologists, molecular
      geneticists and evolutionary biologists rested on the evidence-based assumption
      that reproductive tissues could be ideal environments for the expression and
      transmission of transposable elements that can move into new locations in the
      genome. These elements include DNA transposons and retrotransposons that,
      together, make up over 40% of the human genome. The testis may be a particularly
      good niche for their expression because of the unique dynamic of spermatogenesis,
      where the methylation-demethylation status of germ cell DNA is at its most
      plastic. Hence windows of opportunity can arise that may release transposable
      elements from the tight regulatory control of expression imposed on them by bulk
      DNA methylation. As the testis is where most mutations become embedded in the
      germline, the meeting included a number of keynote presentations that aimed to
      examine the potential for transposable elements to heritably alter the genome and
      effect variation independently of the usual Mendelian mechanisms. In essence,
      could the testis be one of the favoured sites where genomic plasticity makes its
      mark?

PMID- 17511662
TI  - Organization of chromosomes in spermatozoa: an additional layer of epigenetic
      information?
AB  - Elaborate non-random organization of human sperm chromosomes at different
      structural levels, starting from the DNA packing by protamines up to the higher
      order chromosome configuration and nuclear positioning of chromosome territories,
      has been discovered. Here, we put forward a hypothesis that the unique genome
      architecture in sperm provides a mechanism for orchestrated unpacking and ordered
      activation of the male genome during fertilization, thus offering an additional
      level of epigenetic information that will be deciphered in the descendant cells.

PMID- 17511663
TI  - Genomewide identification of nuclear matrix attachment regions: an analysis of
      methods.
AB  - High-throughput technologies now afford the opportunity to directly determine the
      distribution of MARs (matrix attachment regions) throughout a genome. The utility
      of cosmid and oligonucleotide platforms to identify human chromosome 16 MARs from
      preparations that employed LIS (lithium di-iodosalicylic acid) and NaCl
      extraction protocols was examined. The effectiveness of the platforms was then
      evaluated by Q-PCR (quantitative real-time PCR). Analysis revealed that caution
      must be exercised, since the representation of non-coding regions varies among
      platforms. Nevertheless, several interesting trends were revealed. We expect that
      these technologies will prove useful in systems approaches directed towards
      defining the role of MARs in various cell types and cellular processes.

PMID- 17511664
TI  - Genome plasticity in the mouse oocyte and early embryo.
AB  - In dissecting the molecules and molecular mechanisms that control mammalian
      oocyte-to-embryo transition, we found abundant transcripts representing
      developmentally regulated ERVs (endogenous retroviruses) in mouse oocyte and two
      cell stage embryo cDNA libraries. These retrotransposons can act as alternative
      promoters and first exons for diverse genes, synchronizing their expression.
      Heritable genetic change due to replication of these retrotransposons probably
      occurs specifically in oocytes and early embryos. ERVs are usually epigenetically
      silenced, through DNA methylation and chromatin-based mechanisms. Their
      activation and silencing indicates a change in the epigenetic state of the
      genome. The thousands of endogenous retro-elements in the mouse genome provides
      potential scope for large-scale co-ordinated epigenetic fluctuations and leads to
      the hypothesis that differential transposable element expression triggers
      sequential reprogramming of the embryonic genome during the oocyte-to-embryo
      transition.

PMID- 17511665
TI  - Inheritance of an epigenetic change in the mouse: a new role for RNA.
AB  - Hereditary epigenetic variation, initially recognized and studied extensively in
      plants, had not been reported in mammals until recently. We have now identified
      the Kit locus as the first example of a paramutable gene of the mouse. Kit(+/+)
      homozygotes born from Kit(tm1Alf)(/+) heterozygotes maintain and transmit to
      their progeny the white-spotted phenotype characteristic of the mutant
      heterozygote. Our observation of unusual amounts of RNA in the sperm of the
      paramutated (Kit*) males had led us to consider the possibility of RNA-mediated
      inheritance. A role for RNA was supported further by the efficient establishment
      of the epigenetic modification following microinjection in one-cell embryos of
      either sperm RNA of the paramutated males or of the Kit-specific microRNAs miR
      221 and -222. In this article, we describe the phenotypes associated with the
      wild-type genome in the Kit* paramutated animals. Paramutation may be considered
      to be one possibility of epigenetic modification in the case of familial disease
      predispositions that are not fully accounted for by Mendelian analysis.

PMID- 17511666
TI  - Sperm DNA fragmentation: awakening the sleeping genome.
AB  - We have recently demonstrated that mammalian spermatozoa have the ability to
      degrade their DNA by a mechanism that is similar to apoptosis in somatic cells.
      When this mechanism is activated, the DNA is first degraded into loop-sized
      fragments by TOP2B (topoisomerase IIB). This degradation, termed sperm chromatin
      fragmentation, can be reversed by EDTA, which causes TOP2B to religate the double
      stranded breaks it originally produced. Under certain conditions, a nuclease then
      degrades the sperm DNA further, digesting the entire sperm genome. When mouse
      spermatozoa which have been treated to induce TOP2B-mediated DNA breaks are
      injected into oocytes, the paternal DNA is specifically and completely degraded.
      This total digestion of paternal DNA occurs at the time of DNA synthesis
      initiation. In the present study, we explore the significance of an active TOP2B
      in the nucleus for mouse sperm function.

PMID- 17511667
TI  - Endogenous retrovirus expression in testis and epididymis.
AB  - ERVs (endogenous retroviruses), which comprise 8-10% of mouse and human genomes,
      are present in thousands of copies, ranging in size from complete 9 kb virus to
      truncated partial sequences. Despite well-documented differential expression of
      ERVs in normal and diseased tissues, their biological significance remains
      controversial. Work in this laboratory revealed remarkably high ERV expression in
      mouse epididymis, but not in testis. Similar early studies revealed expression of
      human ERV-E4.1 in both testis and epididymis, but expression of other HERVs
      (human ERVs) was not examined. Using degenerate primers to conserved regions of
      reverse transcriptase specific for each of nine HERV families, we have detected
      expression of six HERV families in epididymis and three in testis. Differential
      HERV expression may reflect the fully differentiated state of epididymal
      epithelium in contrast with the immature germ cell population in the testis.
      These two tissues may therefore lay the groundwork not only for understanding the
      influence of cellular differentiation on HERV expression, but also to reveal
      HERVs that are routinely exposed to sperm.

PMID- 17511668
TI  - RNA dynamics of fertile and infertile spermatozoa.
AB  - The presence of a complex population of mRNAs in human mature spermatozoa is well
      documented; among them, transcripts of aromatase and ERs (oestrogen receptors)
      have been described but their significance is not clear. Therefore, to clarify
      the role of this complex population of mRNAs in human ejaculated sperm, we have
      isolated on discontinuous density gradients two main fractions from the same
      sample: high- and low-motile spermatozoa. The levels of different transcripts
      coding for molecules involved in nuclear condensation [Prm-1 (protamine 1) and
      Prm-2], capacitation [eNOS (endothelial nitric oxide synthase), nNOS (neuronal
      nitric oxide synthase), c-myc], motility and sperm survival (aromatase) have been
      assessed using semi-quantitative RT (reverse transcriptase)-PCR. The viability of
      sperm as well as the percentage of apoptosis were identical in high- and low
      motile fractions. No significant change in the c-myc/Prm-2 ratio between the two
      populations of spermatozoa was observed. Conversely the amount of Prm-1 mRNA was
      significantly higher in low-motile than in high-motile fraction; in most of the
      high-motile sperm samples analysed, eNOS and nNOS transcripts were undetectable,
      whereas they were observed in low-motile sperm. Moreover, a partial or complete
      disappearance of c-myc transcripts was observed after capacitation. As to the
      aromatase expression, a significant decrease in the amount of transcripts in
      immotile sperm fraction was recorded in all samples studied. To conclude,
      analysing mRNA profiles in humans could be helpful either as a diagnostic tool to
      evaluate male fertility, since they reflect spermatogenesis gene expression,
      and/or a prognosis value for fertilization, since these RNAs are delivered to
      oocytes.

PMID- 17511669
TI  - APOBEC3 proteins: major players in intracellular defence against LINE-1-mediated
      retrotransposition.
AB  - Mammalian genomes are littered with enormous numbers of transposable elements
      interspersed within and between single-copy endogenous genes. The only presently
      spreading class of human transposable elements comprises non-LTR (long terminal
      repeat) retrotransposons, which cover approx. 34% of the human genome. Non-LTR
      retrotransposons include the widespread autonomous LINEs (long interspersed
      nuclear elements) and non-autonomous elements such as processed pseudogenes, SVAs
      [named after SINE (short interspersed nuclear element), VNTR (variable number of
      tandem repeats) and Alu] and SINEs. Mobilization of these elements affects the
      host genome, can be deleterious to the host cell, and cause genetic disorders and
      cancer. In order to limit negative effects of retrotransposition, host genomes
      have adopted several strategies to curb the proliferation of transposable
      elements. Recent studies have demonstrated that members of the human APOBEC3
      (apolipoprotein B mRNA editing enzyme catalytic polypeptide 3) protein family
      inhibit the mobilization of the non-LTR retrotransposons LINE-1 and Alu
      significantly and participate in the intracellular defence against
      retrotransposition by mechanisms unknown to date. The striking coincidence
      between the expansion of the APOBEC3 gene cluster and the abrupt decline in
      retrotransposon activity in primates raises the possibility that these genes may
      have been expanded to prevent genomic instability caused by endogenous
      retroelements.

PMID- 17511670
TI  - Glucose metabolic disorder after transplantation.

PMID- 17511671
TI  - Is it risky to use kidneys from CDC-increased risk donors?

PMID- 17511672
TI  - Countries' donation performance in perspective: time for more accurate
      comparative methodologies.

PMID- 17511673
TI  - Intercellular transfer of MHC and immunological molecules: molecular mechanisms
      and biological significance.
AB  - The intercellular transfer of many molecules, including the major
      histocompatibility complexes (MHC), both class I and II, costimulatory and
      adhesion molecules, extracellular matrix organization molecules as well as
      chemokine, viral and complement receptors, has been observed between cells of the
      immune system. In this review, we aim to summarize the findings of a large body
      of work, highlight the molecules transferred and how this is achieved, as well as
      the cells capable of acquiring molecules from other cells. Although a
      physiological role for this phenomenon has yet to be established we suggest that
      the exchange of molecules between cells may influence the immune system with
      respect to immune amplification as well as regulation and tolerance. We will
      discuss why this may be the case and highlight the influence intercellular
      transfer of MHC molecules may have on allorecognition and graft rejection.

PMID- 17511674
TI  - Options for immunologic support of renal transplantation through the HLA and
      immunology laboratories.
AB  - HLA and immunology laboratories are an integral part of clinical kidney
      transplant programs. They assist transplant clinicians with evaluating the
      immunological suitability of potential recipients for transplantation and
      selecting donor-recipient combinations with a low risk of immunological failure.
      With sophisticated new techniques becoming available for posttransplant
      immunological monitoring, laboratories play an increasing supporting role during
      posttransplant follow up. The level of precision at which immunological testing
      predicts clinical outcome, however, leaves room for improvement. In this article,
      we summarize the current state of diagnostics, discuss problems, and point out
      promising developments.

PMID- 17511675
TI  - CD4+CD25+ regulatory T cells in transplantation: progress, challenges and
      prospects.
AB  - The involvement of CD4(+)CD25(+) regulatory T cells (Treg) in general immune
      homeostasis and protection from autoimmune syndromes is now well established.
      Similarly, there has been increasing evidence for Treg involvement in allograft
      rejection and current immunotherapies. However, despite significant advances in
      understanding the development, function, and therapeutic efficacy of Treg in
      certain well-defined rodent models, the relevance of Treg to clinical
      transplantation remains unclear. In this review, we summarize our current
      understanding of the role of Treg in immunity and organ transplantation in
      experimental and clinical settings. In addition, we review advances in using Treg
      as a form of immune therapy. The goal is to highlight the complexities and
      opportunities in the field and to provide evidence to support the use of antigen
      specific Tregs in the context of transplantation to facilitate a robust and
      selective state of immune tolerance.

PMID- 17511676
TI  - American society of transplantation symposium on B cells in transplantation:
      harnessing humoral immunity from rodent models to clinical practice.
AB  - There is growing awareness that B cells and alloantibodies are important
      mediators of both acute and chronic allograft injury. Unfortunately, few
      therapies are clinically available to mitigate the function of B cells or the
      effects of established alloantibody. As a result, many sensitized people await
      transplantation without a suitable donor, and several rejection syndromes are
      emerging that appear to involve B cells either as antibody producers or as
      antigen-presenting cells. In recognition of this unmet need in transplantation,
      the American Society of Transplantation organized a Symposium on B cells in Organ
      Transplantation to foster interest in this topic amongst basic researchers
      attending the annual meeting of the American Association of Immunologists. This
      manuscript will give an overview of the presentations from this symposium
      including the current risks of allosensitization, adaptive accommodation,
      approaches toward B-cell tolerance for allo- and xenoantigens and clinical
      application of these concepts in ABO incompatible neonatal cardiac
      transplantation.

PMID- 17511677
TI  - Antigenic disparity impacts outcome of agonism but not blockade of costimulatory
      pathways in experimental transplant models.
AB  - Treatment regimens consisting of CTLA-4 Ig/anti-CD154 or agonistic anti
      CD28/rapamycin have both been shown to prevent GVHD in fully allogeneic murine
      model systems. Using a transgenic approach to track the fate of host-reactive T
      cells in a minor antigen disparity model of GVHD, we found that while treatment
      with CTLA-4 Ig/anti-CD154 retained efficacy, the costimulation agonist anti-CD28
      combined with rapamycin failed to prevent GVHD. Analysis of the host-reactive
      CD4(+) and CD8(+) T-cell responses revealed that in contrast to CTLA-4Ig/anti
      CD154-treated recipients, host-reactive T cells in recipients treated with
      agonistic anti-CD28/rapamycin displayed enhanced and accelerated T-cell
      proliferation and failed to undergo activation-induced cell death. An increase in
      systemic levels of inflammatory cytokines was observed in the anti-CD28/rapamycin
      treated recipients of the minor but not major antigen disparity bone marrow
      transplants. Our results demonstrate the intricacies of costimulatory receptor
      signaling pathways, and reveal how agonism of the CD28 pathway can have opposing
      outcomes depending on the degree of antigenic disparity.

PMID- 17511678
TI  - Mechanism of NKT cell-mediated transplant tolerance.
AB  - The mechanism by which CD1d-restricted Valpha14 natural killer T (NKT) cells
      participate in transplant tolerance has yet to be completely clarified. Recently,
      we showed that repeated activation of NKT cells by their specific glycolipid
      ligand, alpha-galactosylceramide, leads to a change in function to an immune
      regulatory role with IL-10 production. Moreover, these cells were shown to be
      able to induce regulatory dendritic cells (DCs). In this study, we showed that
      NKT cells from transplant tolerant recipients of cardiac allograft produced
      higher levels of IL-10, which is required for the maintenance of tolerance; this
      was proved by adoptive transfer experiments. In addition, DCs from wild-type (WT)
      tolerant recipients but not NKT cell-deficient recipients showed a higher IL-10
      producing profile, a more immature phenotype, and tolerogenic capability. CD4 T
      cells from WT tolerant recipients but not NKT cell-deficient recipients also
      produced higher levels of IL-10 upon alloantigen stimulation and showed lower
      proliferative activity that was reversed by blocking the IL-10 receptor. These
      data indicate the existence of IL-10-dependent immune regulatory interplay among
      NKT cells, DCs, and CD4 T cells, even in the absence of artificial stimulation of
      NKT cells with synthetic glicolipids, which is required for the maintenance of
      transplant tolerance.

PMID- 17511679
TI  - Induction of Anoikis following myoblast transplantation into SCID mouse muscles
      requires the Bit1 and FADD pathways.
AB  - Seventy-five percent of the myoblasts transplanted in the mouse muscle die during
      the first 4 days following transplantation. The purpose of this study was to
      determine if anoikis plays a role in this phenomenon. Survival and proliferation
      of myoblasts in vitro were determined by Hoescht-PI labeling and cell counts
      respectively. In vivo cell survival and proliferation were quantified by
      injecting human male myoblasts labeled with (14)C-thymidine in SCID mouse
      muscles. Survival and proliferation of the transplanted myoblasts were evaluated
      by scintigraphy and quantitative PCR of human Y chromosomal DNA. Inclusion of the
      extracellular matrix protein fibronectin enhanced transplanted myoblast survival
      by 1.7-fold while vitronectin improved their proliferation by 1.8-fold.
      Reductions in FADD and Bit1 expression reduced anoikis in vitro and improved the
      injected myoblast survival in vivo. Ectopic expression of the anti-apoptotic
      protein Bcl-2 completely abolished myoblast anoikis in vitro and enhanced cell
      survival by 3.1-fold in vivo. Cell death following transplantation appears to me
      mediated in part by anoikis. Inclusion of extracellular matrix proteins enhanced
      both survival and proliferation. Reduced expression of the proapoptotic proteins
      Bit1 and FADD or overexpression of Bcl-2 improved myoblast survival.

PMID- 17511680
TI  - Estimated benefits of transplantation of kidneys from donors at increased risk
      for HIV or hepatitis C infection.
AB  - Kidneys from organ donors who have behaviors that place them at increased risk
      for infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
      are often discarded, even if viral screening tests are negative. This study
      compared policies that would either 'Discard' or 'Transplant' kidneys from
      Centers for Disease Control classified increased-risk donors (CDC-IRDs) using a
      decision analytic Markov model of renal failure treatment modalities. Base-case
      CDC-IRDs were current injection drug users (IDUs) with negative antibody and
      nucleic acid testing (NAT) for HIV and HCV, comprising 5% of kidney donors.
      Compared to a CDC-IRD kidney 'Discard' policy, the 'Transplant' policy resulted
      in higher patient survival, a greater number of quality-adjusted life-years
      (QALYs) (5.6 vs. 5.1 years per patient), more kidney transplants (990 vs. 740
      transplants per 1000 patients) and lower cost of care ($60 000 vs. $71 000 per
      QALY). The total number of viral infections was lower with the 'Transplant'
      policy (13.1 vs. 14.8 infections per 1000 patients over 20 years), because the
      'Discard' policy led to more time on hemodialysis, with a higher HCV incidence.
      We recommend that kidneys from NAT-negative CDC-IRDs be considered for
      transplantation since the practice is estimated to be beneficial from both the
      societal and individual patient perspective.

PMID- 17511681
TI  - Patient and graft survival implications of simultaneous pancreas kidney
      transplantation from old donors.
AB  - We investigated graft and patient survival implications of simultaneous pancreas
      kidney (SPK) transplant from old donors. Data describing patients with type 1
      diabetes mellitus listed for an SPK transplant from 1994 to 2005 were drawn from
      Organ Procurement and Transplant Network registries. Allograft survival, patient
      survival and long-term survival expectations among SPK recipients from young (age
      <45 years) and old (age >/=45 years) donors were modeled by multivariate
      regression. We also examined predictors of reduced early access to young donor
      transplants. Of 16 496 eligible SPK candidates, 8850 patients (53.6%) received an
      SPK transplant and 776 (8.8%) of these transplants were from old donors.
      Reasonable 5-year, death-censored kidney (77.8 %) and pancreas (71.3%) survivals
      were achieved with old donors. SPK transplantation from both young and old donors
      predicted lower mortality compared to continued waiting. An additional expected
      wait of 1.5 years for a young donor equalized long-term survival expectations to
      that achieved with use of old donors. Early allocation of young donor transplants
      declined in the more recent era and varied by region, candidate age, blood type
      and sensitization. We conclude that old SPK donors should be considered for
      patients with decreased access to young donor transplants. Prospective evaluation
      of this practice is needed.

PMID- 17511682
TI  - Early withdrawal of calcineurin inhibitors and rescue immunosuppression with
      sirolimus-based therapy in renal transplant recipients with moderate to severe
      renal dysfunction.
AB  - Mammalian Target-of-Rapamycin inhibitors (mTOR inhibitors) can be used to replace
      the calcineurin inhibitors (CNIs) to prevent progression in chronic kidney
      disease (CKD) following organ transplantation. Discontinuation of tacrolimus in
      136 recipients of kidney transplants with progressive renal dysfunction
      significantly decreased the rate of loss of estimated glomerular filtration rate
      (eGFR, mL/min/1.73 m(2)) (pre-intervention vs. post-intervention slopes, -0.013
      vs. -0.002, p < 0.0001). Discontinuation of tacrolimus was associated with a
      sustained and significant improvement in graft function (pre-eGFR vs. post-eGFR;
      26.0 +/- 1.1 vs. 47.4 +/- 2.1, p < 0.0001) in 74% of patients. This intervention
      was ineffective if the mean and (median) values of creatinine (mg/dL) and eGFR
      were 3.8 +/- 0.2 (3.4) and 18.4 +/- 1.9 (22.4), respectively, at the time of
      conversion therapy. During the follow-up (range, 1.5-34.6, months), a total of 13
      patients had their first acute rejection following the conversion therapy, an
      annual incidence of less than 10% and none of these episodes resulted in graft
      loss. The salutary effects of sirolimus therapy following discontinuation of
      tacrolimus in patients with moderate to severe graft dysfunction due to allograft
      nephropathy even in high-risk patients improves kidney function and prevents
      acute rejection.

PMID- 17511683
TI  - Hepatocellular carcinoma recurrence and death following living and deceased donor
      liver transplantation.
AB  - We examined mortality and recurrence of hepatocellular carcinoma (HCC) among 106
      transplant candidates with cirrhosis and HCC who had a potential living donor
      evaluated between January 1998 and February 2003 at the nine centers
      participating in the Adult-to-Adult Living Donor Liver Transplantation Cohort
      Study (A2ALL). Cox regression models were fitted to compare time from donor
      evaluation and time from transplant to death or HCC recurrence between 58 living
      donor liver transplant (LDLT) and 34 deceased donor liver transplant (DDLT)
      recipients. Mean age and calculated Model for End-Stage Liver Disease (MELD)
      scores at transplant were similar between LDLT and DDLT recipients (age: 55 vs.
      52 years, p = 0.21; MELD: 13 vs. 15, p = 0.08). Relative to DDLT recipients, LDLT
      recipients had a shorter time from listing to transplant (mean 160 vs. 469 days,
      p < 0.0001) and a higher rate of HCC recurrence within 3 years than DDLT
      recipients (29% vs. 0%, p = 0.002), but there was no difference in mortality or
      the combined outcome of mortality or recurrence. LDLT recipients had lower
      relative mortality risk than patients who did not undergo LDLT after the center
      had more experience (p = 0.03). Enthusiasm for LDLT as HCC treatment is dampened
      by higher HCC recurrence compared to DDLT.

PMID- 17511684
TI  - Once-daily tacrolimus extended-release formulation: 1-year post-conversion in
      stable pediatric liver transplant recipients.
AB  - The pharmacokinetics, safety and tolerability of a once-daily formulation of
      tacrolimus (tacrolimus extended-release formulation; XL formerly referred to as
      MR or MR4) were assessed in 18 stable pediatric liver transplant recipients who
      were converted from the twice-a-day formulation of tacrolimus (TAC) to XL.
      Patients received their twice-a-day dose of TAC on study days 1 through 7.
      Beginning on the morning of study day 8, patients were converted to XL on a 1:1
      (mg:mg) basis for their total daily dose, and were maintained on a once-daily AM
      dosing regimen using the same therapeutic monitoring and patient care techniques
      employed with TAC. Based on pharmacokinetic profiles obtained on study days 7
      (TAC) and 14 (XL), steady state exposure (AUC(0-24)) was equivalent between XL
      and TAC; the mean XL/TAC ratio for lnAUC(0-24) was 100.9% (90% CI: 90.8%,
      112.1%). AUC(0-24) and C(min) were strongly correlated at steady state
      (correlation coefficient: XL 0.90, TAC 0.94). During the first year post
      conversion, there were no cases of acute rejection, discontinuation of XL, graft
      loss or death. The safety profile of XL was consistent with that known for TAC.
      These results support the safe and convenient conversion of pediatric liver
      transplant recipients from twice-a-day TAC to once-daily XL.

PMID- 17511685
TI  - Tacrolimus monotherapy without steroids after liver transplantation--a
      prospective randomized double-blinded placebo-controlled trial.
AB  - Early steroid withdrawal after liver transplantation (LT) is desirable in order
      to reduce steroid side effects. Between February 2000 and August 2004, 110
      patients after LT were included in this prospective, randomized, double-blind,
      placebo-controlled trial. Randomization was performed before LT. In all patients,
      tacrolimus was used without induction therapy. All patients received
      methylprednisolon for 14 days, thereafter a double-blinded medication containing
      either placebo (n = 56) or methylprednisolon (n = 54) for 6 months, which was
      completely stopped thereafter. End points were patient and graft survival, acute
      and chronic rejection, and incidence of steroid side effects during the first
      year after LT. One-year patient survival was 85.7% (placebo) and 88.8% (steroid)
      (p = 0.572). Twenty-seven (48.2%) and 19 (35.2%) patients experienced acute
      rejection (placebo versus steroid, respectively; p = 0.116). Two patients in the
      placebo group but none in the steroid group experienced chronic rejection (p =
      0.257). The rates of side effects were (placebo versus steroid, respectively):
      CMV infection 25% versus 33% (p = 0.336), post-transplant diabetes 30% versus 53%
      (p = 0.024), hypertension 39% versus 52% (p = 0.248), hypercholesterolemia 10%
      versus 41% (p = 0.002) and hypertriglyceridemia 32% versus 54% (p = 0.046). In
      conclusion, early steroid withdrawal after LT is feasible under tacrolimus
      monotherapy without increased rejection rates and with a lower rate of side
      effects.

PMID- 17511686
TI  - Changes in international normalized ratio (INR) and model for endstage liver
      disease (MELD) based on selection of clinical laboratory.
AB  - Priority for liver transplantation is based on the Model for Endstage Liver
      Disease (MELD) score, a mathematical function which includes international
      normalized ratio (INR). We present an analysis to determine the lab-to-lab
      variation in INR at 14 clinical laboratories across the United States. We
      performed a survey to identify representative clinical laboratories across the
      United States, where INR was measured in the determination of MELD score. Five
      'standard' samples for INR were formulated and were sent to the 14 clinical
      laboratories to determine variation in INR and MELD score. Among the 14 clinical
      laboratories, the range in INR for the five samples was: sample 1 (1.2-2.0),
      sample 2 (1.4-2.5), sample 3 (1.7-3.4), sample 4 (1.9-3.7) and sample 5 (2.4
      5.1). The range in calculated MELD score was: sample 1 (8-14), sample 2 (10-17),
      sample 3 (12-20), sample 4 (14-21) and sample 5 (16-25). The selection of the
      clinical laboratory used to determine INR may result in substantial changes in
      MELD score independent of severity-of-illness. These data suggest that further
      review of interlaboratory variation in MELD should be undertaken because of the
      potential impact on prioritization for liver transplantation.

PMID- 17511687
TI  - Whole-liver graft without the retrohepatic inferior vena cava for sequential
      (domino) living donor liver transplantation.
AB  - Grafts used in Domino liver transplantation (LT) obtained from living donor liver
      transplantation (LDLT) for familial amyloid polyneuropathy (FAP) patients have
      been mainly used as reduced grafts. Because of small-for-size problems seen in
      LDLT, using whole liver grafts could improve post-LT outcome. Eight consecutive
      Domino LDLT using whole livers without retrohepatic inferior vena cava (IVC) from
      FAP patients were retrospectively analyzed. The graft weight/recipient's body
      weight ratio (GWRW) in the domino recipients ranged from 1.28% to 2.4% (mean:
      1.52). Multiple vascular reconstructions in the whole-liver domino LT resulted in
      longer than usual warm ischemia time (mean: 64 min); however immediate post
      operative recovery of hepatic function was uneventful. At 8-40 months after the
      transplant, all the FAP patients are well and all of the domino recipients are
      alive. Domino LT using a whole FAP liver from a LDLT for a FAP patient presents
      satisfactory results, even though the transplant procedure is technically
      complicated.

PMID- 17511688
TI  - Usefulness of PCR strategies for early diagnosis of Chagas' disease reactivation
      and treatment follow-up in heart transplantation.
AB  - Heart transplantation (HTx) is a useful therapy for end-stage Chagas
      cardiomyopathy; however, Chagas reactivation remains a mayor complication.
      Parasitological methods offer poor diagnostic sensitivity, and use of more
      sensitive tools such as the Polymerase chain reaction (PCR) is usually necessary.
      In the present study, reactivation incidence and PCR usefulness for early
      reactivation diagnosis, as well as for treatment response evaluation during
      follow-up, were analyzed using Strout parasite detection test, in 10 of 222
      consecutive HTx patients suffering Chagas cardiomyopathy. PCR strategies targeted
      to minicircle sequences (kDNA, detection limit 1 parasite/ 10 mL blood) and
      miniexon genes (SL-DNA, 200 parasite/10 mL) were performed to compare parasite
      burdens between samples. No patients received prophylactic antiprotozoal therapy
      (benznidazole). Five patients (50%) exhibited clinical reactivation within a mean
      period of 71.6 days; positive Strout results were observed in most cases
      presenting clinical manifestations. kDNA-PCR was positive 38-85 days before
      reactivation, whereas SLDNA-PCR became positive only 7-21 days later, revealing
      post-HTx parasitic load enhancement present prior to clinical reactivation
      development. Reactivations were successfully treated with benznidazole and
      generated negative PCR results. Results observed in this study indicate the value
      of PCR testing for an early diagnosis of Chagas reactivation as well as for
      monitoring treatment efficacy.

PMID- 17511689
TI  - Human ehrlichiosis in transplant recipients.
AB  - To characterize the impact of immunosuppression on human ehrlichiosis, we
      reviewed cases of ehrlichiosis occurring in transplant recipients and
      immunocompetent patients at three hospitals in Nashville, Tennessee. Between 1998
      and 2006, 15 transplant patients were identified as having ehrlichiosis,
      diagnosed either by whole blood polymerase chain reaction (PCR) (n = 14) or
      serology (n = 1). They were compared with 43 immunocompetent patients diagnosed
      by whole blood PCR. We retrospectively collected demographic and clinical
      information. The species of Ehrlichia (E. ewingii or E. chaffeensis) was
      determined for patients diagnosed by PCR. The 15 transplant recipients with
      ehrlichiosis included 7 kidney recipients, 6 heart recipients, 1 liver recipient
      and 1 lung recipient. Transplant recipients had more infections with E. ewingii
      than immunocompetent patients (23% vs. 5%, p = 0.08). Transplant recipients
      experienced less rash (0% vs. 36%, p = 0.006) and presented with significantly
      lower hepatic enzymes, but more leukopenia and renal dysfunction than
      immunocompetent patients. Doxycycline therapy was started within 48 h of
      presentation in 73% of transplant recipients and 78% of immunocompetent patients
      (p = 0.7). No patient died in either group. Ehrlichia infections can occur in
      transplant recipients who live in an endemic area. With prompt treatment, the
      infected transplant recipients in our study had similar, favorable outcomes
      compared to immunocompetent patients.

PMID- 17511690
TI  - Preemptive therapy of EBV-related lymphoproliferative disease after pediatric
      haploidentical stem cell transplantation.
AB  - The treatment of Epstein-Barr virus (EBV)-related post-transplant
      lymphoproliferative disease (PTLD) after hematopoietic stem cell transplantation
      (HSCT) is still unsatisfactory. We conducted a prospective trial to evaluate the
      impact of routine EBV surveillance and preemptive treatment with the anti-CD20
      monoclonal antibody rituximab on the development of PTLD in pediatric recipients
      of extensively T-cell depleted HSCT from an HLA-haploidentical relative. Twenty
      seven patients were included in the surveillance program, 12 developed EBV DNA
      positivity, with 8 of 12 presenting with sustained viral DNA levels requiring
      treatment with rituximab. Treatment was well tolerated, and induced clearance of
      EBV DNA in all patients. However, 4/8 patients showed a new increase in EBV load,
      coincident with the emergence of CD20(-)/CD19(+) B cells in peripheral blood,
      accompanied by overt PTLD in 3 patients. The latter cleared PTLD after receiving
      donor EBV-specific cytotoxic T-lymphocytes (CTLs), and persist in remission at a
      median 30-month follow-up. EBV-specific T-cell frequency, undetectable at time of
      EBV DNA positivity, was restored by T-cell therapy to levels comparable with
      controls. We conclude that preemptive therapy with rituximab is safe, but only
      partly effective in haplo-HSCT recipients. Patients who progress to PTLD under
      rituximab treatment can be rescued permanently by infusion of EBV-specific CTLs.

PMID- 17511691
TI  - BK virus associated renal cell carcinoma: case presentation with optimized PCR
      and other diagnostic tests.
AB  - Polyomaviruses, including BK and JC viruses, have been associated with graft
      failure, but have not commonly been associated with malignancy. We present a case
      of renal cell carcinoma arising in an allograft kidney, in which the tumor and
      metastasis contain viral DNA. Tumor and biopsy specimens from this patient were
      examined with hematoxylin & eosin, immunohistochemistry (IHC) and in situ
      hybridization (ISH). The results were confirmed by real-time polymerase chain
      reaction (PCR) analysis with BKV primers. Other viruses including herpes simplex
      1-2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and varicella zoster were
      not detected. The presence of BKV DNA in a renal cell carcinoma, including a
      metastatic focus, adds to the evidence that this virus may play a role in cancers
      of the kidney and urinary tract.

PMID- 17511692
TI  - A mouse model of orthotopic vascularized aerated lung transplantation.
AB  - Outcomes after lung transplantation are markedly inferior to those after other
      solid organ transplants. A better understanding of cellular and molecular
      mechanisms contributing to lung graft injury will be critical to improve
      outcomes. Advances in this field have been hampered by the lack of a mouse model
      of lung transplantation. Here, we report a mouse model of vascularized aerated
      single lung transplantation utilizing cuff techniques. We show that syngeneic
      grafts have normal histological appearance with minimal infiltration of T
      lymphocytes. Allogeneic grafts show acute cellular rejection with infiltration of
      T lymphocytes and recipient-type antigen presenting cells. Our data show that we
      have developed a physiological model of lung transplantation in the mouse, which
      provides ample opportunity for the study of nonimmune and immune mechanisms that
      contribute to lung allograft injury.

PMID- 17511696
TI  - Comment on "Developing policy in the face of scientific uncertainty: interpreting
      0.3 microT or 0.4 microT cutpoints from EMF epidemiologic studies" by Kheifets et
      al. in Risk Analysis, 25(4), 927-935.

PMID- 17511698
TI  - Perceived risks from radiation and nuclear testing near Semipalatinsk,
      Kazakhstan: a comparison between physicians, scientists, and the public.
AB  - Determining the difference in perception of risk between experts, or more
      educated professionals, and laypeople is important so that a potential hazard can
      be effectively communicated to the public. Many surveys have been conducted to
      better understand the difference between expert and public opinions, and often
      laypeople exhibit higher perceptions of risk to hazards in comparison to experts.
      This is especially true when health risk is due to radiation, nuclear power, and
      nuclear waste. This article focuses on one section of a risk perception survey
      given to two groups of individuals with a more specialized education (scientists
      and physicians) and laypeople (villagers) in the Semipalatinsk region of
      Kazakhstan. All of these groups live near the former Soviet nuclear test site.
      Originally, it was expected that the scientists and physicians would have similar
      perceptions of radiation risk, while the public perceptions would be higher, but
      this was not always the case. For example, when perceptions of risk pertain to
      the health impacts of nuclear testing or the dose-response nature of radiation
      exposure, the physicians tend to agree with the laypeople, not the scientists.
      The villagers are always the most risk-averse group, followed by the physicians
      and then the scientists. These differences are likely due to different frames of
      reference for each of the populations.

PMID- 17511699
TI  - On the ethical justification for the use of risk acceptance criteria.
AB  - To protect people from hazards, the common safety regulation regime in many
      industries is based on the use of minimum standards formulated as risk acceptance
      or tolerability limits. The limits are seen as absolute, and in principle these
      should be met regardless of costs. The justification is ethical - people should
      not be exposed to a risk level exceeding certain limits. In this article, we
      discuss this approach to safety regulation and its justification. We argue that
      the use of such limits is based on some critical assumptions; that low accident
      risk has a value in itself, that risk can be accurately measured and the
      authorities specify the limits. However, these assumptions are not in general
      valid, and hence the justification of the approach can be questioned. In the
      article, we look closer into these issues, and we conclude that there is a need
      for rethinking this regulation approach - its ethical justification is not
      stronger than for alternative approaches. Essential for the analysis is the
      distinction between ethics of the mind and ethics of the consequences, which has
      several implications that are discussed.

PMID- 17511700
TI  - Socioeconomic vulnerability and adaptation to environmental risk: a case study of
      climate change and flooding in Bangladesh.
AB  - In this article we investigate the complex relationship between environmental
      risk, poverty, and vulnerability in a case study carried out in one of the
      poorest and most flood-prone countries in the world, focusing on household and
      community vulnerability and adaptive coping mechanisms. Based upon the steadily
      growing amount of literature in this field we develop and test our own analytical
      model. In a large-scale household survey carried out in southeast Bangladesh, we
      ask almost 700 floodplain residents living without any flood protection along the
      River Meghna about their flood risk exposure, flood problems, flood damage, and
      coping mechanisms. Novel in our study is the explicit testing of the
      effectiveness of adaptive coping strategies to reduce flood damage costs. We show
      that, households with lower income and less access to productive natural assets
      face higher exposure to risk of flooding. Disparity in income and asset
      distribution at community level furthermore tends to be higher at higher risk
      exposure levels, implying that individually vulnerable households are also
      collectively more vulnerable. Regarding the identification of coping mechanisms
      to deal with flood events, we look at both the ex ante household level
      preparedness for flood events and the ex post availability of community-level
      support and disaster relief. We find somewhat paradoxically that the people that
      face the highest risk of flooding are the least well prepared, both in terms of
      household-level ex ante preparedness and community-level ex post flood relief.

PMID- 17511701
TI  - Consumer selection of food-safety information sources.
AB  - The aim of this study is to examine the preferences of consumers for different
      information sources when they have a question about food safety. On the basis of
      a nationally representative survey conducted in the Netherlands, five distinct
      consumer groups are identified that not only differ on the reported use of
      information sources but also regarding several personality characteristics and
      sociodemographic variables. The empirical results show that two-thirds of the
      consumers are selective in their use of information sources and prefer either
      institutional or social sources. So, multiple information-acquisition patterns
      exist among the general public. The study illustrates how these findings can help
      to develop effective risk communication strategies.

PMID- 17511702
TI  - Cancer anxiety and the perception of risk in alarmed communities.
AB  - Cancer is a significant public health topic and is frequently a factor in public
      reactions to environmental hazards. It may be reasonable to suggest that a unique
      form of health anxiety exists - one specific to cancer. In this article, we
      explore a measure of cancer anxiety that has applicability to risk perception in
      the specific context of communities that are alarmed over suspect cancer rates
      thought to be associated with environmental hazards. A literature search was used
      to identify survey questions previously used to measure cancer worry, fear,
      anxiety, etc. A list of 24 items was employed in a mail survey sent to 30
      communities in which cancer rates were under investigation (part of a broader
      study). An analysis of the dataset of 1,111 responses yields two versions of a
      cancer anxiety scale: one an additive combination of 21 items (alpha= 0.77) and
      the other a two-factor model consisting of nine- and four-item subscales (alpha=
      0.74 and 0.69). The resulting scales are evaluated for their ability to predict
      perception of risk from the environmental hazards in these cases. Controlling for
      age, sex, and cancer status, the scales explain between 2% and 10% of risk
      perception (full R(2) values ranging from 0.17 to 0.24). Given the range of
      concepts required to model risk perception, we conclude that this measure of
      cancer anxiety is sufficiently reliable and robust to be recommended for use in
      circumstances involving hazards associated with cancer. Other uses and further
      development of the measure are discussed.

PMID- 17511703
TI  - Integration of probabilistic exposure assessment and probabilistic hazard
      characterization.
AB  - A method is proposed for integrated probabilistic risk assessment where exposure
      assessment and hazard characterization are both included in a probabilistic way.
      The aim is to specify the probability that a random individual from a defined
      (sub)population will have an exposure high enough to cause a particular health
      effect of a predefined magnitude, the critical effect size (CES). The exposure
      level that results in exactly that CES in a particular person is that person's
      individual critical effect dose (ICED). Individuals in a population typically
      show variation, both in their individual exposure (IEXP) and in their ICED. Both
      the variation in IEXP and the variation in ICED are quantified in the form of
      probability distributions. Assuming independence between both distributions, they
      are combined (by Monte Carlo) into a distribution of the individual margin of
      exposure (IMoE). The proportion of the IMoE distribution below unity is the
      probability of critical exposure (PoCE) in the particular (sub)population.
      Uncertainties involved in the overall risk assessment (i.e., both regarding
      exposure and effect assessment) are quantified using Monte Carlo and bootstrap
      methods. This results in an uncertainty distribution for any statistic of
      interest, such as the probability of critical exposure (PoCE). The method is
      illustrated based on data for the case of dietary exposure to the organophosphate
      acephate. We present plots that concisely summarize the probabilistic results,
      retaining the distinction between variability and uncertainty. We show how the
      relative contributions from the various sources of uncertainty involved may be
      quantified.

PMID- 17511704
TI  - Food safety objectives should integrate the variability of the concentration of
      pathogen.
AB  - The World Trade Organization introduced the concept of appropriate level of
      protection (ALOP) as a public health target. For this public health objective to
      be interpretable by the actors in the food chain, the concept of food safety
      objective (FSO) was proposed by the International Commission on Microbiological
      Specifications for Foods and adopted later by the Codex Alimentarius Food Hygiene
      Committee. The way to translate an ALOP into a FSO is still in debate. The
      purpose of this article is to develop a methodological tool to derive a FSO from
      an ALOP being expressed as a maximal annual marginal risk. We explore the
      different models relating the annual marginal risk to the parameters of the FSO
      depending on whether the variability in the survival probability and in the
      concentration of the pathogen are considered or not. If they are not,
      determination of the FSO is straightforward. If they are, we propose to use
      stochastic Monte Carlo simulation models and logistic discriminant analysis in
      order to determine which sets of parameters are compatible with the ALOP. The
      logistic discriminant function was chosen such that the kappa coefficient is
      maximized. We illustrate this method by the example of the risks of listeriosis
      and salmonellosis in one type of soft cheese. We conclude that the definition of
      the FSO should integrate three dimensions: the prevalence of contamination, the
      average concentration per contaminated typical serving, and the dispersion of the
      concentration among those servings.

PMID- 17511705
TI  - The use of human experience data in the EU risk assessment process.
AB  - The incorporation of human experience data (HD) into the risk assessment process
      is encouraged by various authorities with the aim of improving the robustness of
      the subsequent findings. HD, however, can present in many forms, ranging from
      epidemiological studies to the accumulated experiences from poison centers. This
      diversity of the human experience, combined with the manner in which it may (or
      may not) present, creates several challenges for risk assessors if they are to
      give available HD due weight in the RA process. An evaluation was made of how HD
      has been cited and used within the 64 human health RAs published by the EU to the
      end of 2005. In all RAs, HD had been cited to some degree. But there was no
      consistency between how cited data had subsequently been taken forward and used
      in the evaluation of different endpoints, either between the RAs authored by the
      same or different EU Member States. The lack of any accepted guidance for
      addressing the role that HD can play within the RA process appears to lead to
      this situation. Recommendations are provided on the scope and focus such guidance
      could usefully be expected to take.

PMID- 17511706
TI  - Cognitive and emotional representations of terror attacks: a cross-cultural
      exploration.
AB  - A questionnaire measuring cognitive and affective representations of terror risk
      was developed and tested in Turkey and Israel. Participants in the study were
      university students from the two countries (n= 351). Four equivalent factors
      explained terror risk cognitions in each sample: costs, vulnerability, trust, and
      control. A single negative emotionality factor explained the affective component
      of terror risk representations in both samples. All factors except control could
      be measured reliably. Results supported the validity of the questionnaire by
      showing expected associations between cognitions and emotions, as well as
      indicating gender differences and cultural variations. Current findings are
      discussed in relation to previous results, theoretical approaches, and practical
      implications.

PMID- 17511707
TI  - A meta-analysis of children's hand-to-mouth frequency data for estimating
      nondietary ingestion exposure.
AB  - Because of their mouthing behaviors, children have a higher potential for
      exposure to available chemicals through the nondietary ingestion route; thus,
      frequency of hand-to-mouth activity is an important variable for exposure
      assessments. Such data are limited and difficult to collect. Few published
      studies report such information, and the studies that have been conducted used
      different data collection approaches (e.g., videography versus real-time
      observation), data analysis and reporting methods, ages of children, locations,
      and even definitions of "mouthing." For this article, hand-to-mouth frequency
      data were gathered from 9 available studies representing 429 subjects and more
      than 2,000 hours of behavior observation. A meta-analysis was conducted to study
      differences in hand-to-mouth frequency based on study, age group, gender, and
      location (indoor vs. outdoor), to fit variability and uncertainty distributions
      that can be used in probabilistic exposure assessments, and to identify any data
      gaps. Results of this analysis indicate that age and location are important for
      hand-to-mouth frequency, but study and gender are not. As age increases, both
      indoor and outdoor hand-to-mouth frequencies decrease. Hand-to-mouth behavior is
      significantly greater indoors than outdoors. For both indoor and outdoor hand-to
      mouth frequencies, interpersonal, and intra-personal variability are
      approximately 60% and approximately 30%, respectively. The variance difference
      among different studies is much bigger than its mean, indicating that different
      studies with different methodologies have similar central values. Weibull
      distributions best fit the observed data for the different variables considered
      and are presented in this article by study, age group, and location. Average
      indoor hand-to-mouth behavior ranged from 6.7 to 28.0 contacts/hour, with the
      lowest value corresponding to the 6 to <11 year olds and the highest value
      corresponding to the 3 to <6 month olds. Average outdoor hand-to-mouth frequency
      ranged from 2.9 to 14.5 contacts/hour, with the lowest value corresponding to the
      6 to <11 year olds and the highest value corresponding to the 6 to <12 month
      olds. The analysis highlights the need for additional hand-to-mouth data for the
      <3 months, 3 to <6 months, and 3 to <6 year age groups using standardized
      collection and analysis because of lack of data or high uncertainty in available
      data. This is the first publication to report Weibull distributions as the best
      fitting distribution for hand-to-mouth frequency; using the best fitting exposure
      factor distribution will help improve estimates of exposure. The analyses also
      represent a first comprehensive effort to fit hand-to-mouth frequency variability
      and uncertainty distributions by indoor/outdoor location and by age groups, using
      the new standard set of age groups recommended by the U.S. Environmental
      Protection Agency for assessing childhood exposures. Thus, the data presented in
      this article can be used to update the U.S. EPA's Child-Specific Exposure Factors
      Handbook and to improve estimates of nondietary ingestion in probabilistic
      exposure modeling.

PMID- 17511708
TI  - Semiparametric modeling of the spatial distribution of occupational accident risk
      in the casual labor market, Piracicaba, southeast Brazil.
AB  - The objective of this study was to estimate the spatial distribution of work
      accident risk in the informal work market in the urban zone of an industrialized
      city in southeast Brazil and to examine concomitant effects of age, gender, and
      type of occupation after controlling for spatial risk variation. The basic
      methodology adopted was that of a population-based case-control study with
      particular interest focused on the spatial location of work. Cases were all
      casual workers in the city suffering work accidents during a one-year period;
      controls were selected from the source population of casual laborers by
      systematic random sampling of urban homes. The spatial distribution of work
      accidents was estimated via a semiparametric generalized additive model with a
      nonparametric bidimensional spline of the geographical coordinates of cases and
      controls as the nonlinear spatial component, and including age, gender, and
      occupation as linear predictive variables in the parametric component. We
      analyzed 1,918 cases and 2,245 controls between 1/11/2003 and 31/10/2004 in
      Piracicaba, Brazil. Areas of significantly high and low accident risk were
      identified in relation to mean risk in the study region (p < 0.01). Work accident
      risk for informal workers varied significantly in the study area. Significant
      age, gender, and occupational group effects on accident risk were identified
      after correcting for this spatial variation. A good understanding of high-risk
      groups and high-risk regions underpins the formulation of hypotheses concerning
      accident causality and the development of effective public accident prevention
      policies.

PMID- 17511709
TI  - On the use of hierarchical probabilistic models for characterizing and managing
      uncertainty in risk/safety assessment.
AB  - A general probabilistically-based approach is proposed for both cancer and
      noncancer risk/safety assessments. The familiar framework of the original ADI/RfD
      formulation is used, substituting in the numerator a benchmark dose derived from
      a hierarchical pharmacokinetic/pharmacodynamic model and in the denominator a
      unitary uncertainty factor derived from a hierarchical animal/average
      human/sensitive human model. The empirical probability distributions of the
      numerator and denominator can be combined to produce an empirical human
      equivalent distribution for an animal-derived benchmark dose in external-exposure
      units.

PMID- 17511710
TI  - Some limitations of aggregate exposure metrics.
AB  - Aggregate exposure metrics based on sums or weighted averages of component
      exposures are widely used in risk assessments of complex mixtures, such as
      asbestos-associated dusts and fibers. Allowed exposure levels based on total
      particle or fiber counts and estimated ambient concentrations of such mixtures
      may be used to make costly risk-management decisions intended to protect human
      health and to remediate hazardous environments. We show that, in general,
      aggregate exposure information alone may be inherently unable to guide rational
      risk-management decisions when the components of the mixture differ significantly
      in potency and when the percentage compositions of the mixture exposures differ
      significantly across locations. Under these conditions, which are not uncommon in
      practice, aggregate exposure metrics may be "worse than useless," in that risk
      management decisions based on them are less effective than decisions that ignore
      the aggregate exposure information and select risk-management actions at random.
      The potential practical significance of these results is illustrated by a case
      study of 27 exposure scenarios in El Dorado Hills, California, where applying an
      aggregate unit risk factor (from EPA's IRIS database) to aggregate exposure
      metrics produces average risk estimates about 25 times greater - and of uncertain
      predictive validity - compared to risk estimates based on specific components of
      the mixture that have been hypothesized to pose risks of human lung cancer and
      mesothelioma.

PMID- 17511711
TI  - Bootstrap estimation of benchmark doses and confidence limits with clustered
      quantal data.
AB  - The benchmark dose (BMD) is an exposure level that would induce a small risk
      increase (BMR level) above the background. The BMD approach to deriving a
      reference dose for risk assessment of noncancer effects is advantageous in that
      the estimate of BMD is not restricted to experimental doses and utilizes most
      available dose-response information. To quantify statistical uncertainty of a BMD
      estimate, we often calculate and report its lower confidence limit (i.e., BMDL),
      and may even consider it as a more conservative alternative to BMD itself.
      Computation of BMDL may involve normal confidence limits to BMD in conjunction
      with the delta method. Therefore, factors, such as small sample size and
      nonlinearity in model parameters, can affect the performance of the delta method
      BMDL, and alternative methods are useful. In this article, we propose a bootstrap
      method to estimate BMDL utilizing a scheme that consists of a resampling of
      residuals after model fitting and a one-step formula for parameter estimation. We
      illustrate the method with clustered binary data from developmental toxicity
      experiments. Our analysis shows that with moderately elevated dose-response data,
      the distribution of BMD estimator tends to be left-skewed and bootstrap BMDL s
      are smaller than the delta method BMDL s on average, hence quantifying risk more
      conservatively. Statistically, the bootstrap BMDL quantifies the uncertainty of
      the true BMD more honestly than the delta method BMDL as its coverage probability
      is closer to the nominal level than that of delta method BMDL. We find that BMD
      and BMDL estimates are generally insensitive to model choices provided that the
      models fit the data comparably well near the region of BMD. Our analysis also
      suggests that, in the presence of a significant and moderately strong dose
      response relationship, the developmental toxicity experiments under the standard
      protocol support dose-response assessment at 5% BMR for BMD and 95% confidence
      level for BMDL.

PMID- 17511712
TI  - Health-based population forecasting: effects of smoking on mortality and
      fertility.
AB  - A microsimulation model, allowing one to forecast short- and long-term population
      changes conditional on the prevalence of a risk factor in a population, is
      presented. In this model, population changes result from the aggregation of
      changes in individual event histories, which, in turn, result from mortality and
      infertility rates recalculated in accordance with their known relative risks in
      population groups exposed to a risk factor. Smoking, being the most widespread
      and influential preventable public health risk factor, is chosen to demonstrate
      the abilities of the model to forecast the population effects of different
      hypothetical smoking prevalences. The demographic and population health effects
      on 20-, 50-, and 100-year projections with the current, hypothetically doubled,
      and hypothetically halved the current smoking prevalence are analyzed in detail.
      The model predicts an increase in life expectancy (0.99 year for males and 0.64
      years for females), and an increase in population size (2.2-7.5% dependent on the
      age group) if smoking prevalence is reduced by half. Sensitivity analyses of all
      findings are performed. The generalization of the model to account for multiple
      risk factors (e.g., the simultaneous effects of alcohol consumption, obesity, and
      smoking) and effects on medical expenditures are discussed.

PMID- 17511713
TI  - Discount rates in risk versus money and money versus money tradeoffs.
AB  - We use data from a survey of residents of five Italian cities conducted in late
      spring 2004 to estimate the discount rates implicit in (1) money versus future
      risk reductions and (2) money versus money tradeoffs. We find that the mean
      personal discount rate is 0.3-1.7% in (1) and 8.7% in (2). The latter is lower
      than the discount rates estimated in comparable situations in many recent
      studies, greater than market interest rates in Italy at the time, and exhibits
      modest variation with age and gender. The discount rate implicit in money versus
      risk tradeoffs is within the range of estimates from studies in the United States
      and Europe, and does not depend on observable individual characteristics. We use
      split samples to investigate whether a completely abstract risk reduction - one
      where the risk reduction delivery has been stripped of all specifics, so that
      respondents should focus on the risks without being distracted by details -
      results in WTP and discount figures comparable to those from an identified
      delivery mechanism (a medical test). We find that while WTP for an immediate risk
      reduction is 42-73% higher with the abstract risk reduction, the discount rate in
      the money versus risk tradeoffs and the variance of the error term in the WTP
      equation are the same across the two variants of the questionnaire.

PMID- 17511716
TI  - Report from the 1st Japanese Urological Association-Japanese Society of Medical
      Oncology joint conference, 2006: 'A step towards better collaboration between
      urologists and medical oncologists'.
AB  - The 1st Japanese Urological Association-Japanese Society of Medical Oncology
      Joint Conference, titled 'A step towards better collaboration between urologists
      and medical oncologists', was held to coincide with the 44th Meeting of the Japan
      Society of Clinical Oncology, Tokyo, in October 2006. The main theme of the
      conference addressed the need for a subspecialty of medical oncologist within
      urology to keep abreast of advances in medical oncology. Urologists should become
      more involved in the postoperative management of urologic cancer. Consensus on
      the optimal way to move forward in the treatment of urological cancer is needed.
      The conference featured eight lectures surveying the present status of uro
      oncology in Europe, the USA, Korea, Singapore, and Japan; the relationship
      between surgical oncologists and medical oncologists; global trends and
      international clinical trials in uro-oncology; and the future of urologic
      oncology. These were followed by a general discussion titled 'Achieving better
      collaboration between the surgical oncologist and the medical oncologist.' This
      report presents a roundup of the 1st Japanese Urological Association-Japanese
      Society of Medical Oncology Joint Conference.

PMID- 17511717
TI  - Absence of prophylactic antibiotics in minimum incision endoscopic urological
      surgery (MEUS) of adrenal and renal tumors.
AB  - OBJECTIVE: Recently, some studies suggested that antimicrobial prophylactics
      (AMP) are not needed to prevent surgical site infection (SSI) for clean
      operations despite worldwide acceptance of AMP. However, appropriate use of AMP
      in urological surgery has not been fully studied. Herein, we report an attempt of
      gradual decrease of AMP to non-use of AMP in minimum incision endoscopic
      urological surgery (MEUS) of adrenal and renal tumors. MATERIALS AND METHODS: We
      investigated 95 consecutive patients who underwent 16 MEUS adrenalectomy and 79
      MEUS radical and partial nephrectomy in our hospital. Patients were classified
      into the following three groups by means of prevention of SSI: the first step
      group received ampicillin sodium/sulbactam sodium 1.5 g i.v. 30 min before the
      operation; the second step group received a single 300 mg of levofloxacin orally
      60 min before the operation; and the third step group received no AMP. Clinical
      backgrounds and incidences of SSI were compared among these three groups.
      RESULTS: The first, second and third step groups consisted of 31, 36 and 28
      patients, respectively. There was no statistically significant difference among
      these groups in terms of clinical backgrounds including age, sex, body mass
      index, American Society of Anesthesiologists classification, National Nosocomial
      Infections Surveillance risk index, and type and length of operation. The first
      step group had one superficial SSI that healed without any non-specific
      treatment. None of the second and third step groups had superficial SSI. There
      was no case of deep surgical site or distant infection. CONCLUSION: AMP could be
      discarded in clean MEUS of adrenal and renal tumors without increasing the
      incidence of SSI.

PMID- 17511718
TI  - Urological emergency in neonates with congenital hydronephrosis.
AB  - OBJECTIVE: It is well described that unilateral pelviureteric junction
      obstruction (PUJO) is a benign condition, because the dilatation resolves
      spontaneously and the function does not decrease in most of the kidneys. However,
      there is exceptional PUJO that requires emergent treatment in neonatal periods.
      The aim of this article is to report the urological emergency and management in
      neonates with PUJO. MATERIALS AND METHODS: Nine children (seven boys and two
      girls) with PUJO who underwent neonatal emergent treatment during the last 13
      years were reviewed. Renal function was evaluated according to decay curve of
      serum creatinine (SCr) levels corresponding to gestational age (GA) at delivery.
      Physical examination, ultrasonographic monitoring, and chest and abdominal plain
      radiographs were repeated in each neonate. RESULTS: Eight patients were detected
      prenatally. In five patients, multicystic dysplastic kidney (MCDK) was
      demonstrated on the contralateral side. Three patients underwent percutaneous
      puncture of fetal hydronephrosis. Decrease of amniotic fluid was evident in three
      fetuses. Indications for emergent treatment included mass effect from
      hydronephrosis in three patients, renal dysfunction in five, and severe urinary
      tract infection in one. During neonatal periods, a percutaneous nephrostomy tube
      was placed in seven, and open nephrostomy in one with anorectal malformation.
      Repeated punctures of the dilated renal pelvis were done in one patient. Renal
      function after pyeloplasty was stable in eight patients, while it was moderately
      decreased in one who was associated with oligohydramnios in utero. CONCLUSION:
      Indications for emergent treatment in neonates with PUJO included mass effect
      from giant hydronephrosis, renal dysfunction and severe urinary tract infection.
      At birth, respiratory and circulatory conditions must first be stabilized. In
      neonates with hydronephrosis of the solitary kidney or severe bilateral PUJO,
      serial SCr should be monitored to evaluate renal function. Decrease of amniotic
      fluid suggested renal functional compromise that would not recover after
      urological management.

PMID- 17511719
TI  - Diabetes mellitus and kidney cancer risk: the results of Japan Collaborative
      Cohort Study for Evaluation of Cancer Risk (JACC Study).
AB  - BACKGROUND: Diabetes mellitus (DM) is reported as being a risk factor associated
      with kidney cancer in Western countries. The incidence of both kidney cancer and
      DM is lower in Japan than the other developed countries, albeit on the rise.
      METHODS: We evaluated the risk factors for kidney cancer mortality using the
      database of the Japan Collaborative Cohort Study for Evaluation of Cancer Risk
      (JACC) study. The analytic cohort included 46 462 males and 64 326 females aged
      40-79 years old. The Cox proportional hazards model was used to determine age-
      and sex-adjusted relative risk and its 95% confidence intervals. RESULTS: DM
      showed an increased, age- and sex-adjusted hazard ratio for kidney cancer
      mortality, but it failed to achieve statistical significance after controlling
      for other factors. CONCLUSION: The present study showed that DM increased the
      risk of kidney cancer death among the Japanese population. However, further
      studies may be needed to confirm the findings in the present study because DM
      failed to remain as a significant risk factor after controlling for other factors
      because of the small number of kidney cancer deaths in the present study.

PMID- 17511720
TI  - Clinical outcome of orthotopic neobladder replacement in patients with a solitary
      functioning kidney.
AB  - OBJECTIVE: To evaluate the outcome of orthotopic neobladder creation in patients
      with a solitary functioning renal unit at the time of surgery. METHODS: This
      study included a total of 18 patients (15 men and three women) with a solitary
      functioning kidney who underwent radical cystectomy for invasive bladder cancer
      followed by orthotopic neobladder replacement. Of these, an ileal, ileocolic or
      sigmoid colon neobladder was constructed in 11, three or four patients,
      respectively. Clinical data from these patients were retrospectively reviewed to
      clarify the significance of neobladder creation in patients with a solitary
      functioning kidney. RESULTS: During the observation period of this series (mean,
      44.2 months; range, 15-95 months), there were nine early complications in six
      patients (wound infection, ileus, urine leakage and pulmonary embolism in four,
      three, one and one, respectively) and 10 late complications in nine patients
      (severe metabolic acidosis, vesicourethral anastomotic stricture,
      ureterointestinal anastomotic stricture and neobladder calculi in six, two, one
      and one, respectively). Severe metabolic acidosis occurred in six (five ileal
      neobladders and one ileocolic neobladder); however, there were no significant
      differences in preoperative renal function and serum electrolytes as well as
      postoperative voiding function between patients with and without severe metabolic
      acidosis. These six patients required administration of sodium bicarbonate, and
      their metabolic status was normalized thereafter. Furthermore, there were no
      significant differences in renal function and serum electrolytes between these
      two groups throughout the observation period, and none of the patients
      demonstrated renal deterioration. CONCLUSIONS: These findings suggest, despite
      the analysis including a small number of patients with a short follow-up period,
      orthotopic neobladder replacement could provide comparatively satisfactory
      results in patients with a solitary functioning kidney; hence, a solitary kidney
      should not be regarded as a contraindicated factor for neobladder creation after
      radical cystectomy.

PMID- 17511721
TI  - Head-to-head comparison of retropubic, perineal and laparoscopic radical
      prostatectomy.
AB  - OBJECTIVE: As more patients are diagnosed with prostate cancer at an early stage,
      it is becoming increasingly important to refine the technique of surgical
      excision. For this purpose we have generated objective data comparing three
      different surgical approaches used by three experienced surgeons. METHODS: We
      prospectively compared three contemporary personal series of 50 consecutive
      radical prostatectomy (RP) patients. The health-related quality of life was
      evaluated preoperatively and in months 1, 3, 6, 12 and 24. RESULTS: Considering
      in turn the patients undergoing retropubic, perineal and laparoscopic RP, the
      median procedure time was 2 h and 27 min, 1 h and 50 min and 4 h, with a
      transfusion rate of 2, 0 and 8%, respectively. In the perineal group there were
      more wound infections. Median catheter drainage was 7, 10 and 7 days and zero, 13
      and one patients needed reinsertion of a catheter. Early continence varied
      considerably, with 57.4, 11.4 and 6.3% of patients pad-free after 1 month, but
      there were no differences in social continence (zero or one pad) with 97.8, 97.8
      and 91.9% after 2 years. The Litwin score for incontinence (preoperative minus
      postoperative) was -24, -41 and -63% after 1 month and -13, +3 and -29% after 2
      years. Twenty-nine, five and 15 patients had a preoperative five-item version of
      International Index of Erectile Function (IIEF-5) score of > or = 17 points and a
      nerve-sparing procedure. After 2 years, 48.1, 0 and 0% had an IIEF-5 score of >
      or = 17 points without the use of phosphodiesterase type 5 (PDE-5) inhibitors,
      but when including patients using inhibitors there were no significant
      differences. CONCLUSIONS: A comparison of morbidity, short-term convalescence and
      long-term side-effects of different surgical techniques is strongly biased by
      both the preoperative status of patients and the skill of the surgeons. Overall,
      we found some differences in the short-term results (e.g. early continence) and
      comparable long-term results.

PMID- 17511722
TI  - Population-based screening for prostate cancer by measuring total serum prostate
      specific antigen in Iran.
AB  - OBJECTIVE: To report the results from an Iranian large population-based
      randomized study of screening using prostate-specific antigen (PSA) to detect
      prostate cancer. MATERIALS AND METHODS: A total of 3758 Iranian men older than 40
      years were mass checked by PSA-based screening. Men with an abnormal digital
      rectal examination (DRE) and serum total PSA level of greater than 4 ng/mL,
      underwent transrectal ultrasonography (TRUS)-guided extended prostate biopsy.
      RESULTS: The PSA value (mean +/- standard deviation, SD) in all men without
      prostate cancer was 1.6 +/- 1.1 ng/mL and in those with cancer 18 +/- 44.8 ng/mL
      (P = 0.001). PSA values increased with age. In those aged 40-49, 50-59, 60-69 and
      > or = 70 years, the mean +/- SD PSA values were 1.3 +/- 0.7, 1.4 +/- 0.8, 1.8 +/
      1 and 2.2 +/- 1.6 ng/mL, respectively. Among the screened men, 323 (8.6%) had a
      serum PSA concentration greater than 4 ng/mL. Of patients who underwent prostate
      biopsy (230, 71.2%), 129 (positive predictive value, 56.1%) had prostate cancer.
      Additionally, nine cancers were detected among 16 patients with PSA of less than
      4 ng/mL who had a doubtful DRE finding. The overall cancer detection rate was
      3.6%; 1.4% at 40-49, 1.6% at 50-59, 4.2% at 60-69 and 12.9% at >/=70 years.
      Conventional systematic sextant biopsies, which accounted for six of the 10 cores
      in our biopsy scheme, detected 98 (71%) of the cancers. CONCLUSIONS: The Iranian
      male population develops prostate cancer quite commonly if their serum PSA levels
      are greater than 4.0 ng/mL. In this study, 65.9% of the detected cancers were
      clinically significant. The conventional systematic sextant technique may be
      inappropriate for detection of all prostate cancers. The results need to be
      confirmed in other randomized trials.

PMID- 17511723
TI  - Practice patterns regarding prostate cancer and benign prostatic hyperplasia in
      Japanese primary care practitioners.
AB  - OBJECTIVE: Although primary care practitioners (PCP) take an active role in
      diagnosis of prostate disorders in Western countries, how PCP take part in
      management of prostate disease still differs worldwide by country. We
      investigated practice and referral patterns concerning prostate disease among
      Japanese PCP and compared these with reported patterns in the West. METHODS: A 26
      question multiple-choice questionnaire was mailed to 935 PCP in Tokyo for
      anonymous completion. Most items involved prostate cancer screening or management
      of benign prostatic hyperplasia (BPH). RESULTS: The survey was completed by 281
      non-urological practitioners, among whom digital rectal examination was performed
      by 43%. Prostate-specific antigen (PSA) was determined in serum by 89%. For
      asymptomatic men older than 50, serum PSA was determined routinely each year by
      only 17%. When PSA was 4.1-10.0 ng/mL, 70% of respondents immediately referred
      patients to urologists, while 18% did not make a referral unless PSA exceeded
      10.0 ng/mL. Seventy-four percent prescribed medication for benign prostate
      hypertrophy; among these respondents, 87% reported common use of alpha-blockers.
      Although 31% of respondents were aware of the International Prostate Symptom
      Score (IPSS), only 2% used it. CONCLUSIONS: Although Japanese PCP were involved
      increasingly in diagnosis and management of prostate disease, degree and
      proficiency of involvement were too limited and less than in Western countries.
      Continuing medical education appears desirable for PCP in Japan regarding
      prostate disease.

PMID- 17511724
TI  - Effect of androgen deprivation therapy on quality of life in Japanese men with
      prostate cancer.
AB  - OBJECTIVE: We evaluated health-related quality of life (HRQOL) in Japanese men
      receiving androgen deprivation therapy (ADT) for prostate cancer. METHODS: Fifty
      six men were enrolled in this study. HRQOL was prospectively measured before ADT,
      and at 3, 6 and 12 months after treatment began, using a general (36-item Short
      Form Health Survey) and disease-specific (the University of California, Los
      Angeles Prostate Cancer Index) HRQOL questionnaire. RESULTS: In the general HRQOL
      questionnaire, patients with stage B (n = 22) or C (n = 17) disease showed a
      decline in vitality at 6 and 12 months (P < 0.05 for both). Stage D patients (n =
      17) had improvements in bodily pain at 3 and 12 months (P < 0.05 for both),
      vitality at 12 months (P < 0.05), role-emotional at 6 months (P < 0.05), and
      mental health at 3 months (P < 0.05). When clinical stages were not considered,
      there were no significant changes in the 36-item Short-Form Health Survey. As for
      the disease-specific HRQOL, urinary function improved after ADT at 6 and 12
      months (P < 0.05 for both), and urinary bother decreased at 3 (P < 0.05), 6 (P <
      0.005) and 12 months (P < 0.05). Sexual function decreased at 3 (P < 0.05), 6 (P
      < 0.005) and 12 months (P < 0.005) but sexual bother improved at 6 and 12 months
      (P < 0.05 for both). If patients were stratified by clinical stages, similar
      findings were observed. CONCLUSIONS: General HRQOL was mostly unaffected by ADT
      in Japanese men. Disease-specific questions indicated an increase in urinary
      function. Although deterioration of sexual function was marked, most patients did
      not report sexual bother. Our results shed new light on the impact of ADT on
      HRQOL and could provide useful information about patient-centered outcome
      evaluations.

PMID- 17511725
TI  - Treatment of men with urethritis negative for Neisseria gonorrhoeae, Chlamydia
      trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum and
      Ureaplasma urealyticum.
AB  - OBJECTIVE: Some patients with symptomatic non-gonococcal urethritis (NGU) are
      negative for Chlamydia trachomatis, mycoplasmas and ureaplasmas. The optimal
      antimicrobial chemotherapy for such NGU has not fully been elucidated, though
      many studies of antimicrobial chemotherapies for C. trachomatis-positive NGU have
      been performed. We assessed the efficacy of antimicrobial agents that are active
      against C. trachomatis on non-mycoplasmal, non-ureaplasmal and non-chlamydial NGU
      (NMNUNCNGU). METHODS: One hundred men whose first-pass urine samples were
      negative for C. trachomatis, Mycoplasma genitalium, Mycoplasma hominis,
      Ureaplasma parvum, and Ureaplasma urealyticum were treated with levofloxacin,
      gatifloxacin, minocycline, or clarithromycin for 7 days. Urethritis symptoms and
      the presence of polymorphonuclear leukocytes (PMNL) in urethral smears were
      assessed before and after treatment. RESULTS: Eighty-eight (88.0%) of 100 men
      with NMNUNCNGU showed no signs of urethral inflammation after treatment, but two
      men complained of some symptoms of urethritis. Twelve (12.0%) of 100 men had
      significant numbers of PMNL in urethral smears, but five of these 12 men had no
      symptoms of urethritis. The efficacy for normalization of urethral smears was
      90.7% for clarithromycin, 89.7% for levofloxacin, 87.5% for gatifloxacin, and
      75.0% for minocycline. The 12 men who showed signs of urethral inflammation were
      retreated with levofloxacin, gatifloxacin, minocycline or clarithromycin for an
      additional 7 days. The 10 men who returned after the second treatment had
      negative urethral smears. CONCLUSION: Our present findings suggest that
      antimicrobial agents active against C. trachomatis are effective against
      NMNUNCNGU and that a 7-day treatment regimen with an appropriate antimicrobial
      agent may be sufficient to manage patients with NMNUNCNGU.

PMID- 17511727
TI  - Alu sequence variants of the BPY2 gene in proven fertile and infertile men with
      Sertoli cell-only phenotype.
AB  - OBJECTIVE: The basic protein on Y chromosome, 2 gene (BPY2) is implicated in the
      spermatogenic process. Three copies (paralogs) of the BPY2 sequence lie in the
      AZFc region, within huge palindromic repeats consisting of Alu sequences located
      in 5' flanking regions. Our objective was to screen the single nucleotide
      variation of BPY2 gene paralogously. METHODS: Mutation screening of the exons and
      5' flanking region of the BPY2 genes was carried out by polymerase chain reaction
      (PCR) and sequencing in 106 infertile patients with a Sertoli cell-only (SCO)
      phenotype and in 126 fertile men. RESULTS: No sequence variation was detected in
      any of the BPY2 exons. Paralogous A/A/A and mixed A/G genotypes are referred to
      the promoter of the gene. The G/G/G genotype (wild type) was observed at the
      rates of 89.6% (95/106) in the SCO subjects and 96.0% (121/126) in the proven
      fertile subjects. The G/G/G plus mixed A/G paralogous variants and the A/A/A
      paralogous variant were detected in 96.2% (102/106) and 3.8% (4/106) of infertile
      patients with SCO, respectively. The G/G/G plus mixed A/G paralogous variants
      were detected in 100% (126/126) of the fertile controls, with no instances of the
      A/A/A phenotype, and this difference was statistically significant (P = 0.038,
      Fisher's exact test). CONCLUSION: The A/A/A genotype may be associated with the
      SCO phenotype. The alteration of all three copies of BPY2 within the AZFc region
      on the Y chromosome may affect spermatogenic process.

PMID- 17511726
TI  - Self-sterilizing catheters with titanium dioxide photocatalyst thin films for
      clean intermittent catheterization: basis and study of clinical use.
AB  - OBJECTIVE: Clean intermittent catheterization (CIC) requires a large number of
      disposable catheters or a large amount of water and disinfectant. We made
      titanium dioxide (TiO(2))-coated catheters for CIC using technology we have
      developed previously, and examined the photocatalytic antibacterial effect of
      this catheter using only light energy and the safety of this type of catheter for
      practical clinical use. METHODS: TiO(2)-coated catheters were filled with
      bacterial cell suspensions and illuminated with a 15-W black-light lamp for
      testing antibacterial potency. Next, we soaked control toxic materials (zinc
      diethyldithiocarbamate) and the tips of TiO(2)-coated catheters in M05 medium,
      and evaluated cell toxicity from the numbers of V79 colonies in these dilutions.
      Then, bodyweight curves and histological tissue changes were observed over a
      period of time in mouse-transplanted TiO(2)-coated catheters and control
      catheters. Finally, we investigated the use of these TiO(2)-coated catheters in
      18 patients by questionnaire and bacterial culture of TiO(2)-coated catheters and
      control catheters. RESULTS: The survival rate of Escherichia coli in the liquid
      inside the TiO(2) catheter decreased to a negligible level within 60 min under
      ultraviolet (UV)-A illumination. The survival rate of Staphylococcus aureus,
      Pseudomonas aeruginosa and Serratia marcescens also decreased to a negligible
      level within 60 min. V79 cells showed no cytotoxicity of this catheter, and there
      was no difference in bodyweight or foreign body reaction between mouse
      transplanted TiO(2)-coated catheters and control catheters. In a preliminary
      clinical analysis of 18 patients who voluntarily used this catheter, the rate of
      positive bacterial culture of the tips of TiO(2)-coated catheters was 20% versus
      60% for conventional catheters after 4 weeks of use. CONCLUSION: TiO(2)-coated
      silicone catheters were easily sterilized under certain light sources and were
      shown to be safe in an experiment using cultured cells and in animal experiments.
      Sterilizing catheters with TiO(2) photocatalyst thin films are expected to be
      used clinically for clean intermittent catheterization after proper modification
      based on this study.

PMID- 17511728
TI  - Cushing syndrome associated with prostatic tumor adrenocorticotropic hormone
      (ACTH) expression after maximal androgen blockade therapy.
AB  - We report a patient with adenocarcinoma of the prostate, who eventually developed
      Cushing syndrome due to ectopic adrenocorticotropic hormone (ACTH) secretion from
      the tumor. At first, maximal androgen blockade (MAB) therapy was effective for
      the prostate carcinoma, which was positive for prostate-specific antigen (PSA)
      and negative for ACTH on the biopsy specimen. However, 3 years later, the patient
      complained of bilateral leg edema. A chest computed tomographic (CT) scan showed
      bilateral pleural effusion and inflammatory changes, focused on the right upper
      lobe. While his PSA was not elevated, and there were no obvious tumor metastases,
      his serum cortisol and ACTH levels were elevated, without any evidence of lesions
      that could release ectopic ACTH. Two weeks later, the patient complained of
      dyspnea and bilateral pleural effusion, and inflammatory changes were worse.
      Although the patient was administered inhibitors of adrenocorticoid synthesis
      metyrapone, they did not have enough clinical efficiency. Steroid pulse therapy
      was also administered but the patient's severe pneumonia and pleural effusion did
      not improve and he finally died of respiratory failure. In contrast to the
      initial biopsy specimen findings, on autopsy, the tumor was negative for PSA but
      positive for ACTH. Thus, it would appear that the tumor began to produce and
      release ectopic ACTH after therapy, which resulted in the development of Cushing
      syndrome in this patient with prostate carcinoma.

PMID- 17511729
TI  - Case of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome
      associated with nephrocalcinosis and distal renal tubular acidosis.
AB  - Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal
      dominant disorder characterized by hypoparathyroidism, sensorineural deafness and
      renal dysplasia. Herein, we report a case of HDR syndrome associated with
      nephrocalcinosis and distal renal tubular acidosis. A 34-year-old woman was
      admitted to investigate recurrent stone formation and bilateral nephrocalcinosis.
      As a 3-year-old child, she had been diagnosed with HDR syndrome without
      chromosome evaluation. She had spontaneous stone passages on several occasions.
      On laboratory examination, serum calcium and intact parathyroid hormone at lower
      levels. Urinary citrate excretion was extremely low at 51.6 mg/day. On an
      ammonium chloride loading test, complete distal renal tubular acidosis was
      proved. To prevent the nephrocalcinosis from deteriorating, she was given
      potassium-sodium citrate. Since administration, she has not experienced
      spontaneous stone passage or renal colic. Nephrocalcinosis and recurrent
      urolithiasis will strongly affect renal prognosis in this case and we consider
      that citrate medication is an effective therapy in avoiding progress of her
      nephrocalcinosis.

PMID- 17511730
TI  - Epidermoid cyst of the ureter: a case report.
AB  - Epidermal cysts of the upper urinary tract are extremely rare. Only three cases
      have been reported in the published work written in English, Italian or German.
      We encountered a case of an epidermoid cyst in the ureter of a 72-year-old male.
      Findings on urine analysis and radiological examination were useful for
      establishing a correct diagnosis of epidermoid cyst of the urinary tract.

PMID- 17511731
TI  - BRCA2 mutation screening is clinically relevant in breast and early prostate
      cancer families.
AB  - It is known that in some families an association exists between breast and
      prostate cancer. Several reports have suggested that BRCA2 mutations may be
      associated with an increased risk of these cancers. Herein, we report three cases
      of early onset of prostate cancer in families with female and male breast
      cancers. In each case, the familial phenotype is associated with a mutation of
      the BRCA2 gene. More generally, genetic counseling, including screening for BRCA2
      mutations, should become standard practice in kindred with prostate and breast
      cancers.

PMID- 17511732
TI  - Extramedullary relapse of acute lymphoblastic leukemia in childhood to the
      prostate.
AB  - A 6-year-old boy presented with the chief complaints of miction pain and
      pollakisuria. He had a past history of acute lymphoblastic leukemia (ALL), which
      subsided in response to chemotherapy at 3 years of age. Ultrasonography revealed
      urinary retention associated with bilateral hydronephrosis secondary to the
      prostate enlargement. Computed tomography and magnetic resonance imaging showed
      no other abnormal finding. Transrectal needle biopsy showed infiltration of
      leukemic cells in the prostate. Bone marrow puncture and cerebrospinal fluid
      aspiration revealed no leukemic cells, resulting in a diagnosis of extramedullary
      relapse of ALL in the prostate. Although he was successfully treated by
      chemotherapy, irradiation and his voiding function was improved, ALL relapsed in
      the left testis 1 year later. In spite of left orchiectomy, irradiation and
      additional chemotherapy, he died of bone marrow relapse and multiple organ
      failure. Extramedullary relapse of ALL in the prostate is very rare. To our
      knowledge, our case is the first well-documented report in the published work.

PMID- 17511733
TI  - Treatment of a recurrent inguinal lymphocele in a penis cancer patient by
      lymphography and selective ligation of lymphatic vessels.
AB  - We report a case of recurrent inguinal lymphocele formation after inguinal
      lymphadenectomy treated by lymphographic mapping and selective ligation of the
      lymphatic vessels. Lymphographic mapping was performed by puncturing a lymphatic
      vessel at the dorsum of the foot. After isolating the vessels that drained into
      the lymphocele, they were clipped and divided through a small skin incision. The
      described technique showed an instant and complete suspension of the lymph
      secretion with subsequent complete healing. Lymphatic mapping and selective
      ligation of afferent lymphatic vessels proved to be an effective treatment of a
      recurrent inguinal lymphocele.

PMID- 17511734
TI  - Xanthogranulomatous orchitis: review of the published work and report of one
      case.
AB  - Xanthogranulomatous orchitis is an extremely rare inflammatory non-neoplastic
      destructive lesion of the testis. We report a 44-year-old man who presented with
      right scrotal swelling and two discharging sinuses. Testicular tumor markers were
      normal. Scrotal ultrasound showed heterogeneous testicular areas and irregular
      margin of the tunica. Surgical exploration revealed infected, unhealthy
      testicular tissue with necrosis and tumor-like lesion. Orchidectomy was done and
      histopathology showed xanthogranulomatous orchitis.

PMID- 17511735
TI  - Incorporation of TIP (paclitaxel, ifosfamide, cisplatin) into first-line therapy
      for intermediate to poor risk testicular germ cell tumors with unfavorable marker
      decline after initial two cycles chemotherapy: a report of three cases.
AB  - Three patients of advanced-non-seminomatous germ cell tumors (International Germ
      Cell Cancer Collaborative Group classification: poor risk, 2; intermediate, 1)
      without evidence of a second primary germ cell tumor were treated. The patients
      received two cycles of standard BEP (bleomycin, etopside, cisplatin) or VIP/VB
      (etoposide, ifosphamide, cisplatin/vinblastine, bleomycin) therapy first. All
      patients in this trial showed unfavorable marker response to these therapies and
      received four cycles of TIP subsequently. A complete remission was observed in
      all patients. No patient experienced life-threatening toxicity. During the 34
      month observation period, all patients were alive without progression.

PMID- 17511736
TI  - Testicular cancer with tumor thrombus extending to the inferior vena cava
      successfully removed using veno-venous bypass: a case report.
AB  - A 33-year-old man with a left testicular tumor was referred to Shinshu University
      Hospital for advanced therapy. Radiographic imaging revealed multiple metastases
      in the retroperitoneal lymph nodes (RPLN) and bilateral lungs, as well as tumor
      thrombus that extended from the left renal vein to the inferior vena cava (IVC)
      adjacent to the right atrium. After orchidectomy, a diagnosis of embryonal
      carcinoma was made with a clinical stage of T1N2M1bS3, which has a poor
      prognosis, based on the International Germ Cell Cancer Collaborative Group
      consensus. After eight courses of chemotherapy, the patient's tumor markers
      normalized and the lung metastases disappeared, but the RPLN and tumor thrombus
      remained. Retroperitoneal lymph node dissection and thrombectomy were performed
      using a veno-venous bypass (VVB). The pathological examination of the thrombus
      revealed a mature teratoma. The patient has been disease-free since surgery.

PMID- 17511737
TI  - Granular cell tumor of the urethra.
AB  - A 38-year-old woman was referred for urethral tumor treatment. Needle biopsy of
      the tumor was performed. Histologically, the tumor was composed of large
      polygonal cells with eosinophilic and periodic acid-Schiff (PAS)-positive
      granular cytoplasm, indistinct cell margins and small round central nuclei.
      Immunohistochemical staining for S100 protein, vimentin, and neuron-specific
      enolase (NSE) was positive, indicating that it was a granular cell tumor.
      Excision of the tumor including the urethra and appendicovesicostomy using the
      Mitrofanoff principle were performed. There has been no tumor recurrence in the 8
      months after the operation.

PMID- 17511739
TI  - Usefulness of laparo- or retroperitoneoscopic biopsy for retroperitoneal lymph
      node swelling of unknown origin.
AB  - Laparo- or retroperitoneoscopic biopsy was performed for five male patients with
      retroperitoneal lymph node swelling of unknown origin. Previous core needle
      biopsies were useless or inapplicable in all patients. A laparoscopic approach
      was used for two patients, with a retroperitoneoscopic approach for the remaining
      three patients. Sufficient specimens for not only pathological diagnosis but also
      further examinations such as immunophenotyping or DNA analysis were safely
      obtained. Convalescence was satisfactory and all patients were treated
      appropriately according to the resulting diagnosis. This technique should be
      performed by urologists, who are more familiar with laparo- or
      retroperitoneoscopic approach targeting retroperitoneal organs.

PMID- 17511738
TI  - Parenteral ambroxol treatment causes xanthine and calcium oxalate stones in rats.
AB  - INTRODUCTION: Ambroxol (ABX) is known to promote bronchial secretion and is used
      as an expectorant. This study was undertaken to document the connection between
      ambroxol parenteral treatment and bladder stones in rats. MATERIAL AND METHODS:
      Forty-five wild rats (Rattus sp.) were divided into three equal groups. Rats from
      the first and second groups received ABX s.c. during 2 weeks in total doses of 30
      mg/kg per 24 h and 60 mg/kg per 24 h, respectively. Rats from the control group
      received 1 mL of injection solution s.c. One month after the treatment
      termination, animals were sacrificed and urinary tracts without urethra were
      dissected. Stones found in the bladders were measured, weighed and chemically
      analysed. Voiding cystography was performed to exclude pathology of the lower
      urinary tract. Photo documentation was produced. RESULTS: From the first and
      second groups, 33% and 47% of rats, respectively, had solitary stones in the
      bladder. In one case from the second group, there was a huge stone in the bladder
      and urethra. There were no stones in rats from the control group. The mean length
      of stones was 1.38 +/- 0.23 mm and 1.41 +/- 0.60 mm in the first and second
      groups, respectively. Mean stone weight was 1.2 +/- 0.2 x 10(-3) g and 1.44 +/-
      0.54 x 10(-3) g. Stones were composed of 67% of xanthine and 33% of calcium
      oxalate. CONCLUSIONS: Ambroxol parenteral treatment caused xanthine and oxalate
      stone formation. Attention should be paid to the possibility of urinary stone
      formation after long-term ABX treatment.

PMID- 17511740
TI  - Change of blood viscosity and urinary frequency by high water intake.
AB  - Physicians recommend a high water intake to prevent cerebral infarction by
      decreasing blood viscosity. However, there is no evidence that high water intake
      decreases viscosity, although it increases urinary frequency. Therefore, we
      investigated the change of blood viscosity and urinary frequency by high water
      intake. We examined the change of blood viscosity after acute water intake, the
      circadian rhythm of blood viscosity, and the change of early morning blood
      viscosity and urinary frequency after high water intake for 1 week in healthy
      volunteers aged 31-75 years. Blood viscosity decreased transiently by acute water
      intake, but remained within the range of its circadian rhythm. Morning blood
      viscosity did not alter by high water intake for 1 week, although urinary
      frequency increased. Because excessive water intake increases urinary frequency
      without decreasing blood viscosity, a high water intake should not be recommended
      in persons with urinary frequency.

PMID- 17511741
TI  - Usefulness of oral wash specimens for detecting Chlamydia trachomatis from high
      risk groups in Japan.
AB  - Orogenital sex is recognized as a route for the transmission of Chlamydia
      trachomatis (CT) which thus causes male chlamydial urethritis. Patients with a
      pharyngeal CT infection have no gross lesions, but CT was tested by pharyngeal
      swabs. In this study, the usefulness of oral wash specimens for detecting CT was
      compared to that of swab specimens. In addition, oral wash specimens were also
      used to screen for CT pharyngeal infection. Eighteen female commercial sex
      workers in whom CT was detected from pharyngeal swabs were re-examined using both
      methods. The positive rate for CT was 44% by swabs and 61% by oral wash
      specimens. Forty-eight male students with CT-positive urine were also screened
      for pharyngeal CT infection. The positive rates were 6% by swabs and 10% by oral
      wash specimens. Our findings therefore indicate that oral wash specimens more
      effectively detected pharyngeal CT infection than pharyngeal swabs.

PMID- 17511742
TI  - Significance of phentolamine redosing during prostaglandin E1 penile color
      Doppler ultrasonography in diagnosis of vascular erectile dysfunction.
AB  - Recently, it was reported that phentolamine redosing during penile duplex can
      abolish a false diagnosis of venous leakage in patients with impotence. The aim
      of this study is to identify any useful role of phentolamine redosing in
      diagnosis of venogenic impotence. Sixty-seven consecutive patients complaining of
      weak erection for at least 6 months were included in this study. Penile color
      Doppler ultrasound (CDU) was performed using a 7.5 MHz linear array transducer
      with a color flow mapping capability. Following intracavernous injection of 20
      microg prostaglandin E1 (PGE1), all patients with persistent end diastolic
      velocity (EDV) >5 cm/sec with an erectile response of E3 or lower, 20 min after
      intracavernosal injection of PGE1, were asked to revisit our clinic for a second
      CDU, 2 weeks later. During initial CDU examination, all 67 patients experienced
      poor response to 20 microg PGE1 with their average peak systolic velocity (PSV)
      and EDV being 42.8 and 6.6 cm/sec, respectively. The second CDU examination had
      similar results to the first one. Addition of 2 mg phentolamine did not
      significantly change the PSV and EDV of cavernosal arteries in any of the 67
      patients. In conclusion, addition of intracavernous phentolamine during PGE1 CDU
      examination carries no advantage over the use of PGE1 alone regarding cavernosal
      artery response in patients with suspected venogenic EDV.

PMID- 17511743
TI  - A microtubule-facilitated nuclear import pathway for cancer regulatory proteins.
AB  - Nuclear protein import is dependent on specific targeting signals within cargo
      proteins recognized by importins (IMPs) that mediate translocation through the
      nuclear pore. Recent evidence, however, implicates a role for the microtubule
      (MT) network in facilitating nuclear import of the cancer regulatory proteins
      parathyroid hormone-related protein (PTHrP) and p53 tumor suppressor. Here we
      assess the extent to which MT and actin integrity may be generally required for
      nuclear protein import for the first time. We examine 10 nuclear-localizing
      proteins with diverse IMP-dependent nuclear import pathways, our results
      indicating that the cytoskeleton does not have a general mechanistic role in
      nuclear localization sequence-dependent nuclear protein import. Of the proteins
      examined, only the p110(Rb) tumor suppressor protein Rb, together with p53 and
      PTHrP, was found to require MT integrity for optimal nuclear import. Fluorescence
      recovery after photobleaching experiments indicated that the MT-dependent nuclear
      transport pathway increases both the rate and extent of Rb nuclear import but
      does not affect Rb nuclear export. Dynamitin overexpression experiments implicate
      the MT motor dynein in the import process. The results indicate that, additional
      to IMP/diffusion-dependent processes, certain cancer regulatory proteins utilize
      an MT-enhanced pathway for accelerated nuclear import that is presumably required
      for their nuclear functions.

PMID- 17511745
TI  - All three trimester binge alcohol exposure causes fetal cerebellar purkinje cell
      loss in the presence of maternal hypercapnea, acidemia, and normoxemia: ovine
      model.
AB  - BACKGROUND: The third trimester equivalent has been identified, both in rat and
      sheep models, as a period of cerebellar vulnerability to alcohol-mediated injury.
      We wished to determine whether alcohol exposure throughout gestation results in
      greater injury compared with exposure limited to the third trimester equivalent.
      While this question has previously been addressed in the rat model, where the
      third trimester equivalent occurs postnatally, it has not yet been addressed in
      an animal model where all 3 trimester equivalents occur prenatally, as in the
      ovine. We also wished to correlate cerebellar Purkinje cell loss to alcohol
      mediated alterations in maternal arterial pH and blood gases as these responses
      might be important mechanistically in mediating the damage. METHODS: Three groups
      of pregnant sheep were used: an untreated normal control group, a saline control
      group, and an alcohol group (1.75 g/kg of the body weight). The alcohol exposure
      regimen was designed to mimic a human binge pattern; alcohol was administered
      intravenously on 3 consecutive days, followed by 4 days without alcohol,
      beginning day 4 of gestation, continuing to the end of the third trimester
      equivalent of human brain growth, day 132 of gestation. RESULTS: All 3 trimester
      alcohol-exposed fetal brains exhibited significant deficits in cerebellar volume
      and Purkinje cell number compared with those of control subjects. We did not
      detect a difference in the reduction of Purkinje cell number when comparing
      between all 3 trimester and third trimester alcohol exposure studies. The
      neuronal loss was accompanied by maternal hypercapnea, acidemia, and normoxemia.
      CONCLUSIONS: These findings demonstrate in an ovine model where all 3 trimester
      equivalent of brain growth occur in utero that the fetal cerebellar Purkinje
      cells are more sensitive to the timing of alcohol exposure and less so to the
      duration of exposure. Decreases in maternal P(a)O(2) were not detected,
      suggesting that maternal hypoxia does not play a role in fetal Purkinje cell
      loss. And finally, we conclude that alcohol-induced changes in maternal arterial
      pH may play a role in alcohol-mediated developmental brain injury.

PMID- 17511744
TI  - Acute ethanol administration rapidly increases phosphorylation of conventional
      protein kinase C in specific mammalian brain regions in vivo.
AB  - BACKGROUND: Protein kinase C (PKC) is a family of isoenzymes that regulate a
      variety of functions in the central nervous system including neurotransmitter
      release, ion channel activity, and cell differentiation. Growing evidence
      suggests that specific isoforms of PKC influence a variety of behavioral,
      biochemical, and physiological effects of ethanol in mammals. The purpose of this
      study was to determine whether acute ethanol exposure alters phosphorylation of
      conventional PKC isoforms at a threonine 674 (p-cPKC) site in the hydrophobic
      domain of the kinase, which is required for its catalytic activity. METHODS: Male
      rats were administered a dose range of ethanol (0, 0.5, 1, or 2 g/kg,
      intragastric) and brain tissue was removed 10 minutes later for evaluation of
      changes in p-cPKC expression using immunohistochemistry and Western blot methods.
      RESULTS: Immunohistochemical data show that the highest dose of ethanol (2 g/kg)
      rapidly increases p-cPKC immunoreactivity specifically in the nucleus accumbens
      (core and shell), lateral septum, and hippocampus (CA3 and dentate gyrus).
      Western blot analysis further showed that ethanol (2 g/kg) increased p-cPKC
      expression in the P2 membrane fraction of tissue from the nucleus accumbens and
      hippocampus. Although p-cPKC was expressed in numerous other brain regions,
      including the caudate nucleus, amygdala, and cortex, no changes were observed in
      response to acute ethanol. Total PKCgamma immunoreactivity was surveyed
      throughout the brain and showed no change following acute ethanol injection.
      CONCLUSIONS: These results suggest that ethanol rapidly promotes phosphorylation
      of cPKC in limbic brain regions, which may underlie effects of acute ethanol on
      the nervous system and behavior.

PMID- 17511746
TI  - Alcohol use disorders increase the risk for mechanical ventilation in medical
      patients.
AB  - BACKGROUND: Annually, more than 300,000 patients receive mechanical ventilation
      in an intensive care unit in the United States. The hospital mortality for
      ventilated patients may approach 50%, depending on the primary diagnosis. In
      trauma and surgical patients, a diagnosis of alcohol use disorder (AUD) is common
      and is associated with a prolonged duration of mechanical ventilation. The
      objective of this study is to determine whether the presence of AUD and the
      development of alcohol withdrawal are associated with an increased use and
      duration of mechanical ventilation in patients with medical disorders that
      commonly require intensive care unit admission. METHODS: We performed a
      retrospective cohort study using the Nationwide Inpatient Sample, a large all
      payer inpatient database representing approximately 1,000 hospitals. For the
      years 2002 to 2003, adult patients with 1 of the 6 most common diagnoses
      associated with medical intensive care unit admission were included in the study.
      Both univariate analysis and multivariable logistic regression were performed to
      determine whether AUD and alcohol withdrawal were independently associated with
      the use and duration of mechanical ventilation in these patients. RESULTS: There
      were a total 785,602 patients who fulfilled 1 of the 6 diagnoses, 26,577 (3.4%)
      had AUD, 3,967 (0.5%) had alcohol withdrawal, and 65,071 (8.3%) underwent
      mechanical ventilation (53% <96 hours, 47%> or =96 hours). Independent of the
      medical diagnosis, AUD was associated with an increased risk of requiring
      mechanical ventilation (13.7 vs 8.1%, odds ratio=1.49, 95% confidence interval
      [1.414; 1.574], p<0.0001) but was not associated with a prolonged duration of
      mechanical ventilation. However, the presence of alcohol withdrawal was
      associated with a longer duration of mechanical ventilation (57 vs 47%> or =96
      hours, odds ratio=1.48, 95% confidence interval [1.266; 1.724], p<0.0001).
      CONCLUSIONS: In patients with medical diagnoses associated with intensive care
      unit admission, AUD increases the risk for mechanical ventilation while the
      development of alcohol withdrawal is associated with a longer duration of
      mechanical ventilation.

PMID- 17511747
TI  - Propensity for obtaining alcohol through shoulder tapping.
AB  - BACKGROUND: Underage youth often obtain alcohol from adults who illegally provide
      the alcohol. One method for obtaining alcohol from adults is shoulder tapping,
      where youth approach an adult outside an alcohol establishment and ask the adult
      to purchase alcohol for them. The goal of this study was to assess what
      percentage of the general and youth-targeted adult population approached outside
      of a convenience/liquor store will agree to purchase and then provide alcohol to
      individuals who appear under age 21. METHODS: We conducted 2 waves of pseudo
      underage shoulder tap request attempts, using requesters who were age 21 or older
      but appeared 18 to 20 years old. In both waves, requests were conducted at
      randomly selected liquor and convenience stores, requesters explained that the
      reason they were asking the adult was because they did not have their
      identification with them, and requesters asked the adults to purchase a 6-pack of
      beer. During wave 1, we conducted 102 attempts, with the requester approaching
      the first adult entering the store alone. During wave 2, we conducted 102
      attempts where the requester approached the first casually dressed male entering
      the store alone who appeared to be 21 to 30 years old. RESULTS: During wave 1, 8%
      of the general sample of approached adults provided alcohol to the pseudo
      underage requesters. The odds of adults providing alcohol in urban areas were 9.4
      times greater than in suburban areas. During wave 2, 19% of the approached young
      men provided alcohol to the requesters. No requester, request attempt,
      establishment, or community characteristics were associated with request attempt
      outcomes during wave 2. CONCLUSIONS: A small percentage of the general population
      of adults will agree to provide alcohol to underage youth when approached outside
      an alcohol establishment. The likelihood of underage youth obtaining alcohol
      through shoulder tapping increases substantially if the youth approach young men.

PMID- 17511748
TI  - Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal:
      a double-blind, randomized, placebo-controlled multicenter pilot study.
AB  - OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol
      dependence and often requires intensive medical treatment. Antiepileptic drugs
      (AEDs) have been shown to be as efficacious in the treatment of AWS in several
      controlled trials as benzodiazepines and superior to placebo in relieving alcohol
      withdrawal symptoms. Oxcarbazepine (OXC), a newer anticonvulsive drug, has a
      favorable safety profile over carbamazepine (CBZ) and other older AEDs due to its
      excellent efficacy and better side-effect profile. METHODS: The efficacy and
      tolerability of OXC versus placebo were investigated in 50 inpatients during a 6
      day treatment of alcohol withdrawal in a 4-site, double-blind, randomized,
      placebo-controlled pilot study. The amount of rescue medication of clomethiazole
      (CLO) capsules needed was chosen as the primary variable. The data were collected
      between May 2003 and September 2004. RESULTS: No initial differences were found
      regarding sociodemographic data and alcohol-related parameters, indicating
      successful randomization. No differences were found in the need for rescue
      medication CLO, decrease of withdrawal symptoms, or craving for alcohol between
      the OXC and the placebo group. Subjectively experienced side effects,
      normalization of vegetative parameters, craving, or improvement of
      psychopathological parameters were not different between the groups. CONCLUSION:
      Despite the negative finding, which may be attributable to the design of the
      study, OXC still poses an interesting alternative to CBZ and other drugs because
      other studies have found it not only as efficient but also as having no addictive
      potential, while additionally possessing an anti-craving effect. Therefore, well
      designed investigations with larger cohorts are required to further elucidate
      this issue.

PMID- 17511749
TI  - Genuine episodic memory deficits and executive dysfunctions in alcoholic subjects
      early in abstinence.
AB  - BACKGROUND: Chronic alcoholism is known to impair episodic memory function, but
      the specific nature of this impairment is still unclear. Moreover, it has never
      been established whether episodic memory deficit in alcoholism is an intrinsic
      memory deficit or whether it has an executive origin. Thus, the objectives are to
      specify which episodic memory processes are impaired early in abstinence from
      alcohol and to determine whether they should be regarded as genuine memory
      deficits or rather as the indirect consequences of executive impairments.
      METHODS: Forty recently detoxified alcoholic inpatients at alcohol entry
      treatment and 55 group-matched controls underwent a neuropsychological assessment
      of episodic memory and executive functions. The episodic memory evaluation
      consisted of 3 tasks complementing each other designed to measure the different
      episodic memory components (learning, storage, encoding and retrieval, contextual
      memory, and autonoetic consciousness) and 5 executive tasks testing capacities of
      organization, inhibition, flexibility, updating, and integration. RESULTS:
      Compared with control subjects, alcoholic patients presented impaired learning
      abilities, encoding processes, retrieval processes, contextual memory and
      autonoetic consciousness. However, there was no difference between the 2 groups
      regarding the storage capacities assessed by the rate of forgetting. Concerning
      executive functions, alcoholic subjects displayed deficits in each executive task
      used. Nevertheless, stepwise regression analyses showed that only performances on
      fluency tasks were significantly predictive of some of the episodic memory
      disorders (learning abilities for 40%, encoding processes for 20%, temporal
      memory for 21%, and state of consciousness associated with memories for 26%) in
      the alcoholic group. DISCUSSION: At alcohol treatment entry, alcoholic patients
      present genuine episodic memory deficits that cannot be regarded solely as the
      consequences of executive dysfunctions. These results are in accordance with
      neuroimaging findings showing hippocampal atrophy. Moreover, given the
      involvement of episodic memory and executive functions in alcohol treatment,
      these data could have clinical implications.

PMID- 17511751
TI  - Enhancing the validity and utility of randomized clinical trials in addictions
      treatment research: III. Data processing and statistical analysis.
AB  - PURPOSE: This is the third paper in a series that reviews strategies for
      optimizing the validity and utility of randomized clinical trials (RCTs) in
      addictions treatment research. Whereas the two previous papers focused on design
      and implementation, here we address issues pertaining to data processing and
      statistical analysis. SCOPE: Recommendations for enhancing data quality and
      utility are offered in sections on data coding and entry; and data format,
      structure and management. We discuss the need for preliminary data analyses that
      examine statistical power; patterns of attrition; between-group equivalence; and
      treatment integrity and discriminability. We discuss tests of treatment efficacy,
      as well as ancillary analyses aimed at explicating treatment processes.
      CONCLUSIONS: Safeguards are necessary to protect data quality, and advance
      planning is needed to ensure that data formats are compatible with statistical
      objectives. In addition to treatment efficacy, statistical analyses should
      evaluate study internal and external validity, and investigate the change
      mechanisms that underlie treatment effects.

PMID- 17511750
TI  - Time course of elevated ethanol intake in adolescent relative to adult rats under
      continuous, voluntary-access conditions.
AB  - BACKGROUND: Adolescence is a period of elevated alcohol consumption in humans as
      well as in animal models. Previous studies in our laboratory have shown that
      adolescent Sprague-Dawley rats consume approximately 2 times more ethanol on a
      gram per kilogram basis than adult animals in a 2-bottle choice free-access
      situation. The purpose of the present study was to examine the time course and
      pattern of elevated ethanol intake during adolescence and the adolescent-to-adult
      transition, contrast this intake with ontogenetic patterns of food and water
      intake, and determine whether adolescent access to ethanol elevates voluntary
      consumption of ethanol in adulthood. METHODS: Adolescent [postnatal day (P)27-28]
      and adult (P69-70) male Sprague-Dawley rats were singly housed with continuous
      access to both water and 1 of 3 experimental solutions in ball-bearing-containing
      sipper tubes: unsweetened ethanol (10% v/v), sweetened ethanol (10% v/v+0.1% w/v
      saccharin), and saccharin alone (0.1% w/v). RESULTS: Ethanol consumption
      plateaued at approximately 7.5 g/kg/d during the first 2 weeks of measurement
      (i.e., P28-39) in early adolescence, before declining sharply at approximately
      P40 to levels that were only modestly elevated compared with adult-typical
      consumption patterns that were reached by approximately P70. In contrast, intake
      of food and total calories showed a more gradual decline into adulthood with no
      distinguishable plateaus in early adolescence. When adolescent-initiated and
      adult-initiated animals were tested at the same chronological age in adulthood,
      animals drank similar amounts regardless of the age at which they were first
      given voluntary access to ethanol. CONCLUSIONS: Taken together, these data
      suggest that the elevated ethanol intake characteristic of early-to-mid
      adolescence is not simply a function of adolescent-typical hyperphagia or
      hyperdipsia, but instead may reflect age-related differences in neural substrates
      contributing to the rewarding or aversive effects of ethanol, as well as possible
      modulatory influences of ontogenetic differences in sensitivity to novelty or in
      ethanol pharmacokinetics. Voluntary home cage consumption of ethanol during
      adolescence, however, was not found to subsequently elevate ethanol drinking in
      adulthood.

PMID- 17511752
TI  - Enhancing the validity and utility of randomized clinical trials in addictions
      treatment research: II. Participant samples and assessment.
AB  - PURPOSE: This paper is the second in a series that describes strategies for
      optimizing the validity and utility of randomized clinical trials (RCTs) in
      addictions treatment research. Whereas the first paper focused on treatment
      implementation and research design, here we address issues pertaining to
      participant samples and assessment methods. SCOPE: With respect to participant
      samples, sections focus on the definition of study populations; informed consent;
      sample size and statistical power; recruitment and enrollment; sample retention;
      and participant tracking systems. Assessment topics include eligibility screening
      and baseline assessment; treatment-related variables; outcome measures; the
      frequency of follow-up evaluation; and assessment process. A final section
      highlights the importance of pilot testing. CONCLUSIONS: Sample recruitment and
      retention strategies are needed that safeguard both internal and external
      validity. Daily estimation assessment procedures are recommended because of their
      versatility for creating a range of outcome measures. Assessment batteries should
      include measures that permit the investigation of treatment processes and
      mechanisms of action.

PMID- 17511753
TI  - A systematic review of patient inflammatory bowel disease information resources
      on the World Wide Web.
AB  - BACKGROUND AND AIMS: The Internet is a widely used information resource for
      patients with inflammatory bowel disease, but there is variation in the quality
      of Web sites that have patient information regarding Crohn's disease and
      ulcerative colitis. The purpose of the current study is to systematically
      evaluate the quality of these Web sites. METHODS: The top 50 Web sites appearing
      in Google using the terms "Crohn's disease" or "ulcerative colitis" were included
      in the study. Web sites were evaluated using a (a) Quality Evaluation Instrument
      (QEI) that awarded Web sites points (0-107) for specific information on various
      aspects of inflammatory bowel disease, (b) a five-point Global Quality Score
      (GQS), (c) two reading grade level scores, and (d) a six-point integrity score.
      RESULTS: Thirty-four Web sites met the inclusion criteria, 16 Web sites were
      excluded because they were portals or non-IBD oriented. The median QEI score was
      57 with five Web sites scoring higher than 75 points. The median Global Quality
      Score was 2.0 with five Web sites achieving scores of 4 or 5. The average reading
      grade level score was 11.2. The median integrity score was 3.0. CONCLUSIONS:
      There is marked variation in the quality of the Web sites containing information
      on Crohn's disease and ulcerative colitis. Many Web sites suffered from poor
      quality but there were five high-scoring Web sites.

PMID- 17511754
TI  - Usefulness of a combined evaluation of the serum adiponectin level, HOMA-IR, and
      serum type IV collagen 7S level to predict the early stage of nonalcoholic
      steatohepatitis.
AB  - OBJECTIVE: Since nonalcoholic steatohepatitis (NASH) may progress to cirrhosis,
      it is important to differentiate NASH from simple steatosis, especially in its
      early stages. However, a liver biopsy cannot be performed in all patients with
      nonalcoholic fatty liver disease (NAFLD). We herein investigated whether serum
      biochemical markers are useful for predicting early-stage NASH. METHOD: Nineteen
      patients with simple steatosis and 66 patients with early-stage NASH (stage 1-2
      in Brunt's criteria) were studied. The area under the receiver operating
      characteristic curve (AUC) was used to illustrate the diagnostic ability of serum
      biochemical parameters to distinguish between simple steatosis and early-stage
      NASH. RESULTS: The serum adiponectin level was found to be significantly lower
      with early-stage NASH group (3.6 mug/mL) than in the simple steatosis group (6.0
      mug/mL) (P < 0.001). The AUC was high (0.765) in the early-stage NASH group, and
      it was also the highest among all other markers. The sensitivity of the serum
      adiponectin level in the diagnosis of early-stage NASH was 68%, which was higher
      than for any other factors, while its specificity was 79%. The corresponding
      sensitivity and specificity of HOMA-IR were 51% and 95%, respectively. For type
      IV collagen 7S, sensitivity was 41% and specificity 95%. The sensitivity of the
      combination of three markers was 94%, with a specificity of 74%. CONCLUSION:
      Approximately 90% of the patients with early-stage NASH can be predicted by a
      combined evaluation of the serum adiponectin level, HOMA-IR, and serum type IV
      collagen 7S level.

PMID- 17511755
TI  - Gastrointestinal symptoms in patients with end-stage renal disease undergoing
      treatment by hemodialysis or peritoneal dialysis.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of
      gastrointestinal symptoms in patients with end-stage renal disease undergoing
      hemodialysis (HD) or peritoneal dialysis (PD) treatment. METHODS: Patients
      undergoing HD or chronic ambulatory PD in the Department of Renal Medicine of our
      hospital were asked to complete a locally validated Rome II questionnaire. The
      same questionnaire was also administered to age- and gender-matched medical
      outpatients without renal failure, and community subjects. Patients on HD and
      their outpatient controls also completed the Hospital Anxiety and Depression
      Scale. RESULTS: A total of 148 patients with end-stage renal disease (HD 100, PD
      48) completed the study. Their results were compared with those of 148 age- and
      gender-matched medical outpatients without renal failure and 148 randomly
      selected community controls. Patients on dialysis treatment were more likely to
      have abdominal pain, use laxatives, and report symptoms consistent with
      functional vomiting and irritable bowel syndrome (IBS) (70%, 55%, 16%, and 25%)
      than age- and gender-matched medical outpatients without renal failure (21%, 11%,
      1%, and 6%) and community controls (16%, 4%, 0%, and 8%). Among HD patients and
      their outpatient controls, the differences appeared to be unrelated to anxiety or
      depression. CONCLUSIONS: Abdominal pain, laxative use, functional vomiting, and
      IBS were more common in uremic individuals than in controls without renal
      failure. Our data have not shown whether these differences are due to the uremic
      state itself, or, alternatively, its treatment.

PMID- 17511756
TI  - Tricyclic antidepressants and the risk of reflux esophagitis.
AB  - OBJECTIVE: Incompetence of the lower esophageal sphincter (LES) is a key factor
      in the pathogenesis of gastroesophageal reflux disease (GERD). Drugs with
      anticholinergic properties, such as tricyclic antidepressants (TCAs), may
      facilitate GERD by a relaxing effect on the LES. AIM: To investigate whether the
      use of TCAs is associated with an increased risk of reflux esophagitis (RE).
      METHOD: A population-based case-control study was conducted within a large Dutch
      primary care database over the period 1996-2005. Cases with endoscopy-confirmed
      RE were identified and matched with up to 10 controls on gender, age, GP
      practice, and calendar time. Exposure to TCAs was assessed in the year prior to
      diagnosis and categorized as current (last prescription covered or ended within
      one month prior to the index date), past, and no use. The relative risk of RE was
      estimated by odds ratios (OR) with 95% confidence intervals (95% CI) using
      multivariate conditional logistic regression analysis. RESULTS: During the study
      period, 1,462 cases with endoscopy-confirmed RE were identified. The risk of RE
      was increased in current TCA users (OR(adj) 1.61, 95% CI 1.04-2.50). Drug
      specific analyses revealed that only clomipramine was associated with an
      increased risk of RE (OR(adj) 4.6, 95% CI 2.0-10.6) in a duration- and dose
      dependent manner (OR(adj) 7.1, 95% CI 2.7-19.2 for use >180 days and OR(adj) 9.2,
      95% CI 1.6-51.5 for >1 DDD equivalent/day). CONCLUSION: No association was
      observed between the risk of RE and the use of TCAs other than clomipramine. The
      association between RE and clomipramine might be drug-related or a result of the
      underlying indication.

PMID- 17511757
TI  - Treatment of choroidal neovascularization using intravitreal bevacizumab.
AB  - PURPOSE: This study aimed to assess the pharmacodynamic profile of intravitreal
      bevacizumab in relation to best corrected visual acuity (BCVA), foveal thickness,
      and other aspects of macular morphology after intravitreal injection of
      bevacizumab in eyes with subretinal choroidal neovascularization (CNV). METHODS:
      A retrospective observational, uncontrolled case series including 26 eyes in 25
      patients followed for up to 6 months after intravitreal injection of bevacizumab
      1 mg repeated as deemed necessary after monthly assessments by biomicroscopy,
      optical coherence tomography, colour fundus photography, fluorescein angiography
      and BCVA determination. At follow-up, cases were classified by morphological
      treatment response (reduction or elimination of pathological neovascular leakage,
      retinal thickening or serous retinal detachment) or absence of response
      (deterioration or lack of improvement). Primary disease entities included age
      related macular degeneration (22 eyes, four of which had evidence of retinal
      angiomatous proliferation), idiopathic peripapillary neovascularization (one
      eye), and angioid streaks (three eyes in two patients). RESULTS: One month after
      the first injection, apparent morphological improvement was observed in 24/26
      eyes and mean BCVA had improved by 3.1 +/- 7.8 letters (p = 0.05). Of these 24
      responders, which included all primary diagnoses, 11 (46%) demonstrated BCVA
      improvement of >or= 5 letters. The two non-responders (7.7%) had lost > 3 lines
      of vision at 2 months follow-up. Overall, 18 eyes completed 6 months follow-up,
      with a mean BCVA improvement of 0.5 +/- 12.7 letters, and 22 eyes completed 3
      months follow-up, with a mean BCVA improvement of 2.0 +/- 11.0 letters. Two
      months after the first injection, 11 (46%) of the 24 responders demonstrated
      signs of recurrent CNV activity, defined as decreased BCVA and/or increased
      retinal thickness and/or fluorescein angiographic CNV leakage. No serious drug
      related adverse events were observed during the course of the study. CONCLUSIONS:
      Overall mean BCVA remained stable throughout the study. Morphological signs of
      reduced CNV activity were seen in the majority of eyes at 2-4 weeks after
      intravitreal bevacizumab injection. Half the responders showed signs of renewed
      CNV activity at 2 months after their first injection. All first-injection
      responders were also second-injection responders.

PMID- 17511758
TI  - Checklist: passport, plane ticket, organ transplant.
AB  - Recently, active and proposed US medical insurance programs are taking steps to
      address the problems of organ availability, long waiting times, and high medical
      and surgical costs by promoting transplant tourism. Such programs are created
      explicitly to encourage policy holders to travel to a foreign country for the
      purpose of obtaining a transplant. Some medical insurance programs have gone as
      far as to bundle exotic travel and healthcare-transplantation not excluded-into
      one package. This article details some of the safety and ethics issues with these
      programs.

PMID- 17511759
TI  - Prophylactic bisphosphonate treatment prevents bone fractures after liver
      transplantation.
AB  - A randomized controlled prospective open-label single center trial was performed.
      At the time of transplantation patients were randomly assigned to one of two
      treatment arms: The study group of 47 patients received zoledronic acid (ZOL, 8
      infusions at 4 mg during the first 12 months after LT), calcium (1000 mg/d) and
      vitamin D (800 IE/d). The control group consisted of 49 patients who received
      calcium and vitamin D at same doses (CON). The incidence of bone fractures or
      death was predefined as the primary endpoint. Secondary endpoints included bone
      mineral density (BMD), serum biochemical markers of bone metabolism, parameters
      of trabecular bone histomorphometry and mineralization density distribution
      (BMDD). Patients were followed up for 24 months. Analysis was performed on an
      intention-to-treat basis. The primary endpoint fracture or death was reached in
      26% of patients in the ZOL group and 46% in the CON group (p = 0.047, log rank
      test). Densitometry results were different between the groups at the femoral neck
      at 6 months after LT (mean+/-SD BMD ZOL: 0.80 +/- 0.19 g/cm2 vs. CON: 0.73 +/-
      0.14 g/cm2, p = 0.036). Mixed linear models of biochemical bone markers showed
      less increase of osteocalcin in the ZOL group and histomorphometry and BMDD
      indicated a reduction in bone turnover. Prophylactic treatment with the
      bisphosphonate zoledronic acid reduces bone turnover and fractures after liver
      transplantation.

PMID- 17511760
TI  - Retroversus implantation of a liver graft: a novel approach to the deceased donor
      with situs inversus totalis.
AB  - Situs inversus totalis is a rare anatomical abnormality that results in
      dextrocardia, mirror image of normal abdominal organs and other congenital
      abnormalities. Deceased donors with this condition are often declined on anatomic
      concerns. While there have been numerous reports of successful liver
      transplantation in recipients with situs inversus, review of the world's
      literature provided only three case reports using deceased donors with situs
      inversus. In this report, a novel approach to implantation of a liver graft from
      a donor with situs inversus is presented. To avoid possible torsion and blockage
      of venous outflow, a modified retroversus piggyback technique with 180 degrees
      ventral caudal (backwards) rotation of the liver graft along the axis of the vena
      cava was performed. This orientation resulted in the retro hepatic vena cava
      facing anteriorly and the larger anatomic liver lobe in the right upper quadrant.
      Excellent outcome was achieved without technical difficulty. Retroversus
      implantation of a liver graft from a donor with situs inversus is safe and
      effective and associated with favorable outcome.

PMID- 17511761
TI  - Contrasting effects of cyclosporine and rapamycin in de novo generation of
      alloantigen-specific regulatory T cells.
AB  - The outcome of T-cell-mediated responses, immunity or tolerance, critically
      depends on the balance of cytopathic versus regulatory T (T(reg)) cells. In the
      creation of stable tolerance to MHC incompatible allografts, reducing the
      unusually large mass of donor-reactive cytopathic T effector (T(eff)) cells via
      apoptosis is often required. Cyclosporine (CsA) blocks activation-induced cell
      death (AICD) of T(eff) cells, and is detrimental to tolerance induction by
      costimulation blockade, whereas Rapamycin (RPM) preserves AICD, and augments the
      potential of costimulation blockade to create tolerance. While differences
      between CsA and RPM in influencing apoptosis of activated graft-destructive
      T(eff) cells are apparent, their effects on graft-protective T(reg) cells remain
      enigmatic. Moreover, it is unclear whether tolerizing regimens foster conversion
      of naive peripheral T cells into alloantigen-specific T(reg) cells for graft
      protection. Here we show, using reporter mice for T(reg) marker Foxp3, that RPM
      promotes de novo conversion of alloantigen-specific T(reg) cells, whereas CsA
      completely inhibits this process. Upon transfer, in vivo converted T(reg) cells
      potently suppress the rejection of donor but not third party skin grafts. Thus,
      the differential effects of RPM and CsA on T(eff) and T(reg) cells favor the use
      of RPM in shifting the balance of aggressive to protective type alloimmunity.

PMID- 17511762
TI  - In defense of transplantation: a reply to nancy Scheper-Hughes.

PMID- 17511763
TI  - The relationship of anti-MICA antibodies and MICA expression with heart allograft
      rejection.
AB  - The role of MICA antibodies in acute heart allograft rejection was examined
      utilizing 190 pre- and post-transplant serum samples from 44 patients collected
      during the first year after transplantation. MICA antibodies were detected by CDC
      test on recombinant cell lines and by the newly developed Luminex MICA antibody
      detection assay. Additionally, MICA expression was analyzed by 'real time' RT-PCR
      and by immunohistochemistry in 10 endomyocardial biopsies. Only two subjects had
      HLA antibodies post-transplant. Nevertheless, MICA antibodies were found in a
      significant number of subjects. The prevalence of MICA antibodies was
      significantly higher among those with severe acute rejection (AR) than in those
      without rejection (60.7% vs. 14.3%, p = 0.0038 by CDC; 55.5% vs. 5.7%, p = 0.0020
      by Luminex). In most cases, the appearance of MICA antibodies post-transplant
      precedes AR. Following transplantation, MICA up-regulation correlated with
      histological evidence of severe rejection. Monitoring for MICA antibodies post
      transplant may be useful to establish new risk factors for acute rejection.

PMID- 17511764
TI  - First forearm transplantation: outcome at 3 years.
AB  - We here report on the surgical procedure, postoperative course and functional
      results at 3 years following the first bilateral forearm transplantation. A 41
      year-old male underwent bilateral forearm transplantation on February 17, 2003.
      After ATG induction therapy, tacrolimus, prednisone and MMF were given for
      maintenance immunosuppression. At 16 months, MMF was switched to everolimus. Hand
      function, histology, immunohistochemistry, radiomorphology, motor and nerve
      conduction and somatosensory-evoked potentials were investigated at frequent
      intervals. A total of six rejection episodes required treatment with either
      steroids, basiliximab, ATG, alemtuzumab or tacrolimus dose augmentation. At 3
      years, the patient is free of clinical signs of rejection despite a persisting
      minimal perivascular lymphocytic dermal infiltrate. No signs of myointimal
      proliferation in graft vessels were seen. Motor function continuously improved,
      resulting in satisfactory hand function. Intrinsic hand muscle function was first
      observed at 16 months and continues to improve. Although discrimination of hot
      and cold recovered, overall sensitivity remains poor. The patient is satisfied
      with the outcome. Bilateral forearm transplantation represents a novel
      therapeutic option after loss of forearms.

PMID- 17511765
TI  - Long-term follow-up of submucosal tunnel and serosa-lined extramural tunnel
      ureter implantation in ileocaecal continent cutaneous urinary diversion (Mainz
      pouch I).
AB  - OBJECTIVE: To assess upper urinary tract complications and renal function in
      patients with a submucosal tunnel and serosa-lined extramural tunnel ureter
      implantation during the long-term follow-up of ileocaecal continent cutaneous
      urinary diversion (Mainz pouch I). PATIENTS AND METHODS: In all, 458 patients who
      had diversion with the ileocaecal pouch were analysed in a retrospective follow
      up study. Uretero-intestinal implantation was done using a submucosal tunnel (ST)
      in 809 reno-ureteric units (RUs) and by the serosa-lined extramural tunnel (ET)
      technique in 74 RUs. The median age of the patients at the time of surgery was
      47.1 years, and the median follow-up was 89.0 months. RESULTS: For the ST, there
      was anastomotic obstruction in 59 RUs (7.3%) at a median of 16.8 months after
      diversion; the obstruction-free intervals at 1, 5 and 10 years were 97%, 93% and
      91%, respectively. Obstruction rates were 13.9% for previously dilated upper
      tracts and 17.1% in patients with a neurogenic bladder. Serum creatinine levels
      were < or =1.6 mg/dL in 97% of the patients at the latest follow-up. For ET,
      there was anastomotic obstruction in three RUs (4.1%) at a median of 17.2 months
      after diversion. Obstruction-free intervals at 1, 5 and 10 years were 100%, 96%
      and 96%. Preoperative dilation of the upper tracts did not reduce the obstruction
      rate (3.1%), but it was 7.1% in patients with a neurogenic bladder. Serum
      creatinine levels were < or =1.6 mg/dL in 98% of the patients at the latest
      follow-up. CONCLUSIONS: The ET gives lower obstruction rates than the ST,
      especially when upper tracts are dilated and in patients with a neurogenic
      bladder. Renal function remained stable with both techniques in the long term.

PMID- 17511766
TI  - Cryotherapy for the prostate: an in vitro and clinical study of two new
      developments; advanced cryoneedles and a temperature monitoring system.
AB  - OBJECTIVES: To assess the characteristics of two new developments in cryotherapy
      for the prostate, IceRods (Oncura, Amersham, UK; 17 G cryoneedles with an
      advanced heat exchanger which produces a precise ice-ball comparable in size to
      those with larger diameter cryoneedles) and the Multitemp 1601 temperature
      monitoring system (TMS, InvivoSense, Trondheim, Norway) probes, in an in vitro
      model and in a clinical setting, to assess their usefulness, focusing in
      particular on the TMS probes. PATIENTS, MATERIALS AND METHODS: We assessed the
      temperature profile and performance of the IceRods in several different
      configurations, in conjunction with the TMS probes for temperature mapping, in a
      phantom prostate model. Subsequently 20 patients with prostate cancer were
      treated with cryosurgery either as a primary or secondary treatment for radiation
      failure; all had a standard treatment protocol. The temperatures throughout the
      procedure were recorded accurately and analysed. RESULTS The IceRods were better
      able to freeze tissue, reaching lower temperatures than conventional cryoneedles.
      The IceRods were also capable of forming ice-balls with a maximum diameter of >6
      cm after freezing at full power for 10 min. The TMS probes depicted real-time
      temperature gradients over either four or eight points in a linear array,
      enabling more thorough monitoring of the temperature changes during a treatment
      cycle. In the clinical setting, in all 20 patients, therapeutic freezing of <-40
      degrees C was achieved in both the cycles. Temperatures of approximately - 40
      degrees C were attained in the area just outside the prostate, as measured by the
      TMS probes, but with variation along the longitudinal axis. The rectal and
      external urinary sphincter temperatures did not fall below 0 degrees C at any of
      the points along the eight-point temperature probe, but there was variation in
      temperature along the prostate. CONCLUSION: IceRods and the TMS probes are
      clinically useful, requiring fewer cryoneedles and with more efficient
      temperature monitoring; this would be expected to reduce morbidity and increase
      safety without compromising an adequate oncological outcome. The IceRods were
      useful in larger prostates of >3.5 cm long, which obviated the need for a 'pull
      back' technique. The TMS probes showed convincingly the variation in temperatures
      along one line, suggesting that single-point temperature monitoring might not
      accurately depict the lowest temperatures reached during treatment, which is
      particularly important in the rectum. This is a significant development in
      cryosurgery and would make the procedure safer, reproducible and allow interested
      clinicians to learn the technique safely and more quickly.

PMID- 17511767
TI  - Duloxetine compared with placebo for treating women with symptoms of overactive
      bladder.
AB  - OBJECTIVE: To evaluate duloxetine (a serotonin-noradrenaline reuptake inhibitor)
      in women with symptoms of overactive bladder (OAB), as it has been shown to
      increase the bladder capacity in an animal model. PATIENTS AND METHODS: In all,
      306 women (aged 21-84 years) were recruited and randomly assigned to placebo
      (153) or duloxetine (80-mg/day for 4 weeks increased to 120-mg/day for 8 weeks;
      153). Symptoms of OAB were defined as bothersome urinary urgency and/or urge
      urinary incontinence (UI) for > or =3 months. Participants were also required to
      have a mean daytime voiding interval (VI) of < or=2 h and urodynamic observations
      of either detrusor overactivity (DOA) or urgency which limited bladder capacity
      to <400 mL, both with no stress UI (SUI). The primary efficacy analysis compared
      the treatment effects on mean change from baseline to endpoint in the mean number
      of voiding episodes (VE)/24 h. The secondary efficacy analyses compared the
      treatment effects on the number of UI episodes (IE)/24 h, in the Incontinence
      Quality of Life questionnaire (I-QOL) score, and on the mean daytime VI. Safety
      was assessed with vital signs, adverse event reporting, routine laboratory
      testing, electrocardiogram, and the measurement of postvoid residual urine
      volumes (PVR). RESULTS: Patients randomized to duloxetine had significant
      improvements over those randomized to placebo for decreases in VE and IE, for
      increases in the daytime VI, and for improvements in I-QOL scores at both doses
      of duloxetine. Urodynamic studies showed no significant increases in maximum
      cystometric capacity or in the volume threshold for DOA. The most common
      treatment-emergent adverse events with duloxetine (nausea, 31%; dry mouth, 16%;
      dizziness, 14%; constipation, 14%; insomnia, 13%; and fatigue, 11%) were the same
      as those reported by women with SUI and were significantly more common with
      duloxetine than placebo. Laboratory assessments, vital signs and
      electrocardiograms were stable relative to baseline, with no relevant differences
      detected between groups. There was a significant difference in the change in PVR
      with duloxetine (<5 mL mean increase) but no patient reported hesitancy or
      retention. CONCLUSION: In this trial, duloxetine was better than placebo for
      treating women with 'wet' and 'dry' symptoms of OAB associated with DOA or a
      bladder capacity of <400 mL.

PMID- 17511768
TI  - Nocturia, nocturia indices and variables from frequency-volume charts are
      significantly different in Asian and Caucasian men with lower urinary tract
      symptoms: a prospective comparison study.
AB  - OBJECTIVE: To describe and compare the patterns of nocturia in Asian and
      Caucasian men presenting with lower urinary tract symptoms (LUTS), and to
      identify associations or correlations between LUTS and variables from a frequency
      volume chart (FVC), as nocturia is common among men with LUTS, and analysis of
      FVCs shows nocturnal polyuria and reduced nocturnal bladder capacity (NBC) as the
      predominant causes in Western patients, but there are few comparisons with other
      ethnic groups. PATIENTS AND METHODS: Consecutive men aged > or = 40 years,
      presenting with LUTS and nocturia to an Asian and a Caucasian tertiary centre,
      were recruited prospectively. The men completed the International Prostate
      Symptom Score and a 3-day FVC. Men having had bladder outlet surgery and/or
      receiving anticholinergics were excluded. We computed the nocturia ratio, i.e.
      the nocturnal urine volume/ 24-h urine volume, nocturia index, predicted
      nocturnal voids and NBC index (NBCI), and analysed comparisons and correlations.
      RESULTS: In all, 93 Asian and 200 Caucasian men were recruited prospectively,
      with a similar age and overall severity of LUTS. The nocturia ratio was larger in
      the Caucasian men, whereas the NBCI was larger in the Asians (P < 0.001). The
      prevalence of nocturnal polyuria in men aged > or =60 years (nocturia ratio > or
      =0.3) was significantly higher in the Caucasian population. Conversely, the
      prevalence of reduced NBC appeared to be higher in the Asians (based on a NBCI of
      >2; P < 0.001). CONCLUSIONS: The patterns of nocturia and FVC variables differed
      significantly in age-matched Asian and Caucasian groups. There are also possible
      ethnic differences in the causes of nocturia, with nocturnal polyuria being more
      prevalent in Caucasians.

PMID- 17511769
TI  - Using prostate-specific antigen doubling time in clinical practice.

PMID- 17511770
TI  - Dysfunctional voiding confirmed by transdermal perineal electromyography, and its
      effective treatment with baclofen in women with lower urinary tract symptoms: a
      randomized double-blind placebo-controlled crossover trial.
AB  - OBJECTIVES: To assess the activity of baclofen, a potent gamma-aminobutyric acid
      ergic agonist, against dysfunctional voiding (DV) and lower urinary tract
      symptoms (LUTS) in a clinical trial, as DV is a leading cause of LUTS in women,
      but there is no effective treatment. PATIENTS AND METHODS: We conducted a
      randomized double-blind placebo-controlled crossover trial in 60 women with DV
      and LUTS between January 2003 and January 2006; patients were randomly assigned
      either baclofen 10 mg three times daily, then matching placebo for 4 weeks, or
      matching placebo then baclofen 10 mg three times daily for 4 weeks, separated by
      a 2-week washout period. Voiding diaries and multichannel urodynamics (at
      baseline, 4 and 10 weeks) were used to record the changes of voids/24 h and
      urodynamic variables. The primary efficacy endpoint was the change in voids/24 h,
      and the TL value (log[T/L]), a new electromyographic variables showing the extent
      of DV. Efficacy outcomes at 4 and 10 weeks were compared with the baseline data,
      using a crossover-designed analysis of variance model. RESULTS: The efficacy
      analysis of the treatment showed that baclofen was associated with significantly
      fewer voids/24 h than placebo (mean difference from baseline 5.53 vs 2.70; P =
      0.001) and a significant increase in TL (mean difference from baseline -1.78 vs
      0.01, P = 0.001). No significant adverse events were reported. CONCLUSIONS: A 4
      week course of baclofen significantly reduced the number of voids/24 h and
      increased the TL value in women with DV confirmed by transdermal perineal
      electromyography. These encouraging results suggest that baclofen could be used
      for treating DV in women.

PMID- 17511771
TI  - Photoselective vaporization of the prostate with the potassium-titanyl-phosphate
      laser in men with prostates of >100 mL.
AB  - OBJECTIVES: To assess the efficacy of photoselective vaporization of the prostate
      (PVP) in men with prostates of >100 mL and causing bladder outlet obstruction
      (BOO), using the high-power 80 W potassium-titanyl-phosphate laser (GreenLight
      PV, Laserscope, San Jose, CA, USA), which offers rapid tissue ablation with
      minimal bleeding. PATIENTS AND METHODS: We assessed 54 consecutive patients with
      prostates of >100 mL (mean 135, SD 42, range 100-300) who had PVP between May
      2003 and August 2005. Evaluations before PVP included urine flowmetry, the
      International Prostate Symptom Score (IPSS), a quality-of life (QoL) score,
      prostate-specific antigen (PSA) level, and prostate volume measured by
      transrectal ultrasonography (TRUS). RESULTS: The mean (SD, range) duration of PVP
      was 81.6 (22.9, 39-150) min, the mean energy used for PVP was 278 (60, 176-443)
      kJ and the mean duration of catheterization after PVP was 23.0 (17.1, 0-72) h.
      The mean (sd) maximum urinary flow rate improved from 8.0 (3.1) to 18.2 (8.1),
      18.5 (9.2), 17.9 (7.8) and 19.3 (9.8) mL/s at 3, 6, 12 and 24 months,
      respectively. The IPSS and QoL scores showed similar improvements, and there was
      a statistically significant reduction in PSA level and prostate volume after PVP.
      There was no major complication and no patient had transurethral resection
      syndrome or a blood transfusion. CONCLUSIONS: The 80 W KTP laser PVP offers rapid
      tissue ablation in patients with BOO caused by a large prostate. The short- and
      medium-term outcomes show that this technique can be a viable alternative to open
      prostatectomy.

PMID- 17511772
TI  - Persistent expression of Aurora-A after neoadjuvant hormonal therapy as a
      predictor of a poor clinical outcome in patients undergoing radical prostatectomy
      for prostate cancer.
AB  - OBJECTIVES: To characterize the changes in the expression of Aurora-A protein in
      prostate cancer before and after androgen-withdrawal therapy, and to assess the
      prognostic significance of the Aurora-A expression in patients undergoing radical
      prostatectomy (RP) after neoadjuvant hormonal therapy (NHT). PATIENTS AND
      METHODS: The study included 97 patients with clinically localized prostate cancer
      who received NHT followed by RP. Paired needle biopsy and corresponding RP
      specimens obtained from these patients were analysed for the expression of Aurora
      A protein by immunohistochemical staining. These findings were then evaluated in
      relation to several clinicopathological factors. RESULTS: There were various
      levels of Aurora-A protein expression in most prostate cancer tissues before NHT;
      however, the Aurora-A expression in RP specimens after NHT was significantly down
      regulated compared with that in corresponding needle-biopsy specimens. The
      expression level of Aurora-A in biopsy specimens was significantly associated
      with the biopsy Gleason score, but not with other factors available before RP.
      The Aurora-A expression in the RP specimens correlated significantly with the
      preoperative value of the serum prostate specific antigen and pathological stage,
      but not with any other clinicopathological factors examined. Furthermore, cell
      proliferative activity in the RP specimens, measured by Ki-67 immunostaining, was
      proportional to the expression of Aurora-A. The biochemical recurrence-free
      survival in patients with a persistent Aurora-A expression in RP specimens was
      significantly lower than that in those with a weak Aurora-A expression, but the
      expression level of Aurora-A was not an independent predictor of biochemical
      recurrence. CONCLUSIONS: Despite the lack of any independent significance, the
      expression level of Aurora-A in prostate cancer tissue after NHT, which might
      inversely reflect the therapeutic effect of NHT, could therefore be a useful
      variable for predicting biochemical recurrence in patients undergoing RP.

PMID- 17511773
TI  - Cytokine production of lung cancer cell lines: Correlation between their
      production and the inflammatory/immunological responses both in vivo and in
      vitro.
AB  - Cytokines produced by tumor cells may have various effects on antitumor immune
      responses and tumor growth. In the present study, the cytokine production of 31
      lung cancer cell lines was evaluated, while any correlation with the histological
      type, the induction of tumor-specific cytotoxic T lymphocytes (CTL) in vitro, and
      angiogenesis and the infiltration of inflammatory cells in tumor tissues were
      also examined. Production of interleukin (IL)-1alpha, IL-1beta, IL-4, IL-6, IL-8,
      IL-10, tumor necrosis factor (TNF)-alpha, granulocyte macrophage colony
      stimulating factor (GM-CSF), granulocyte colony stimulating factor, transforming
      growth factor (TGF)-beta and vascular endothelial growth factor (VEGF) in the
      culture supernatant was measured using enzyme-linked immunosorbent assay. Each
      cytokine was produced in a substantial number of the tumor cell lines. In
      particular, IL-6, IL-8, TGF-beta and VEGF were produced in 18 (55%), 29 (94%), 31
      (100%) and 28 (90%) of 31 cell lines, respectively. However, neither IL-4 nor TNF
      alpha was produced at all by any tumor cell line. TGF-beta production was
      significantly higher in adenocarcinoma than in squamous cell carcinoma (P =
      0.03). Immunohistochemical staining revealed the magnitude of macrophage
      infiltration, and angiogenesis in surgically resected tumor tissue specimens
      correlated well with GM-CSF and IL-8 production from the corresponding cell
      lines. Among six lung cancer cell lines, CTL were induced in the three lung
      cancer cell lines that produced a lower amount of TGF-beta (<100 pg/mL). These
      findings suggested that TGF-beta produced by tumor cells could inhibit the
      induction of CTL in vitro. The present results suggest that the production of
      various cytokines from tumor cells might exert various paracrine effects both in
      vivo and in vitro.

PMID- 17511774
TI  - The activation state of human intrahepatic lymphocytes.
AB  - The immune tolerance induced by the liver as an allograft is difficult to
      reconcile with the evidence that the liver selectively accumulates activated T
      cells from the circulation. However, much of this information is based on murine
      liver lymphocytes that were isolated using enzymatic digestion. In the present
      study we made use of a novel resource, the lymphocytes isolated during the
      perfusion of living donor liver lobe prior to transplantation. These healthy
      human liver lymphocytes displayed surface markers indicating a high degree of
      activation of natural killer cells, CD56(+) T cells, CD4(+) T cells and CD8(+) T
      cells. These properties were independent of enzymatic treatment or the details of
      cell isolation. We conclude that the healthy human liver is a site of intense
      immunological activity.

PMID- 17511775
TI  - Hydroxyurea exerts an anti-proliferative effect on T cells but has no direct
      impact on cellular activation.
AB  - Hydroxyurea (HU) is a cytostatic drug which has been used as an anti-HIV agent
      due mainly to its synergistic activity when combined with certain anti
      retrovirals. In addition, HU might have a beneficial effect on parameters
      involved in the pathogenesis of HIV infection, such as immune activation. To test
      this hypothesis, the effect of HU on T cell proliferation and T cell activation,
      as well as the potential association between these two phenomena, were examined
      in an in vitro model. HU exerted a dose-dependent anti-proliferative effect on T
      cells, and modulated the expression of different activation markers. In cells
      exposed to HU, expression of CD25 and CD38 diminished in a dose-dependent manner,
      whereas expression of CD69 increased. However, when the expression of these
      markers was examined separately on proliferating and non-proliferating
      lymphocytes, HU did not exert any significant effect. Thus, the effect of HU on T
      cell activation is not direct and seems to be mediated through its effect on T
      cell proliferation.

PMID- 17511776
TI  - Characterization of the main placental cytokine profiles from HIV-1-infected
      pregnant women treated with anti-retroviral drugs in France.
AB  - Cytokines are involved in regulating HIV-1 infection. They are also placental
      environment major components. We assessed the potential impact of HIV-1 infection
      and/or anti-retroviral drugs on the placental cytokine profiles that may be
      involved in controlling HIV-1 placental dissemination. Placental explants were
      obtained after elective caesarean section from anti-retroviral-treated HIV-1
      infected pregnant women and from HIV-1 non-infected pregnant women. The main
      placental cytokines were assessed for protein secretion in the supernatants of 24
      h placental culture explants and/or in uncultured placental explants for mRNA
      expression levels. The cytokine profiles were different between the HIV-1
      infected and the non-infected groups. Higher medians of leukaemia inhibiting
      factor (LIF), tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 secretion
      were found in the 24-h culture supernatant of term placenta from HIV-1-infected
      women. High median levels of IL-16 and regulated upon activation normal T cell
      expressed and secreted (RANTES) levels were found in both groups. The mRNA
      expression medians were lower for TNF-alpha and IL-8 and higher for stromal cell
      derived factor-1 (SDF-1) in uncultured placental explants from HIV-1-infected
      women. In the HIV-1-infected group, but not in the non-infected group, the
      secretion levels of TNF-alpha and IL-8, as well as their mRNA expression levels,
      were highly positively correlated; furthermore, their secretion levels were
      correlated positively with LIF and IL-10 secretion levels. We found no
      correlation between the cytokine levels and the immunovirological status of the
      HIV-1-infected mothers or the type or duration of treatment. These results
      highlight the potential impact of HIV-1 and of the anti-retroviral treatments on
      the placental cytokines pattern, independently of their anti-viral activity.

PMID- 17511777
TI  - Outcome of influenza vaccination in combat-related post-traumatic stress disorder
      (PTSD) patients.
AB  - Post-traumatic stress disorder (PTSD) is an anxiety disorder that can occur after
      exposure to extreme traumatic experience such as war trauma, and is accompanied
      by fear, helplessness or horror. Exposure to trauma can result in immune
      dysregulation and influence susceptibility to infectious disease as well as
      vaccine efficacy. The aim of the study was to determine the relation of
      psychological stress and the immune response to influenza vaccination in combat
      related PTSD patients (n = 28). Detection of anti-viral antibody titre was
      performed by inhibition of haemagglutination assay. Ex vivo tetramer staining of
      CD8(+) T lymphocytes was used to monitor T cells specific for human leucocyte
      antigen (HLA)-A*0201-restricted influenza A haemagglutinin antigens before and
      after vaccination. Twenty patients showed a fourfold antibody titre increase to
      one or both influenza A viral strains, and 18 of them showed the same response
      for both influenza B viral strains. Ten of 15 healthy controls showed a fourfold
      rise in antibody titre to both influenza A viral strains and eight of them showed
      the same response for both influenza B viral strains. HLA-A*0201(+) PTSD patients
      (n = 10) showed a significant increase of influenza-specific CD8 T cells after
      vaccination. Although those PTSD patients had a lower number of influenza
      specific CD8(+) T cells before vaccination compared to HLA-A*0201(+) healthy
      controls (n = 6), there was no difference in influenza A antibody titre between
      PTSD patients and control subjects before vaccination. The generated humoral and
      cellular immune response in PTSD patients argues against the hypothesis that
      combat-related PTSD in war veterans might affect protection following influenza
      vaccination.

PMID- 17511778
TI  - Optimal assessment of the ability of children with recurrent respiratory tract
      infections to produce anti-polysaccharide antibodies.
AB  - Specific anti-polysaccharide antibody deficiency (SPAD) is an immune disorder.
      Diagnostic criteria have not yet been defined clearly. One hundred and seventy
      six children evaluated for recurrent respiratory tract infections were analysed
      retrospectively. For each subject, specific anti-pneumococcal antibodies had been
      measured with two enzyme-linked immunosorbent assays (ELISAs), one overall assay
      (OA) using the 23-valent pneumococcal polysaccharide vaccine (23-PPSV) as
      detecting antigen and the other purified pneumococcal polysaccharide serotypes
      (serotype-specific assay, SSA) (serotypes 14, 19F and 23F). Antibody levels were
      measured before (n = 176) and after (n = 93) immunization with the 23-PPSV.
      Before immunization, low titres were found for 138 of 176 patients (78%) with OA,
      compared to 20 of 176 patients (11%) with the SSA. We found a significant
      correlation between OA and SSA results. After immunization, 88% (71 of 81) of the
      patients considered as responders in the OA test were also responders in the SSA;
      93% (71 of 76) of the patients classified as responders according to the SSA were
      also responders in the OA. SPAD was diagnosed in 8% (seven of 93) of patients on
      the basis of the absence of response in both tests. Thus, we propose to use OA as
      a screening test for SPAD before 23-PPSV immunization. After immunization, SSA
      should be used only in case of a low response in OA. Only the absence of or a
      very low antibody response detected by both tests should be used as a diagnostic
      criterion for SPAD.

PMID- 17511780
TI  - Fine needle aspiration cytology of an acral myxoinflammatory fibroblastic
      sarcoma: case report with cytological and cytogenetic findings.

PMID- 17511779
TI  - CD8+ T cell activation and differentiation in allergic asthma and the impact of
      cytomegalovirus serological status.
AB  - Allergic asthma is a chronic inflammatory T helper 2 (Th2)-associated disease.
      There is evidence that the atopic milieu affects the development of CD8(+) T
      cells in patients. We therefore analysed activation and differentiation states of
      CD8(+) T cells in asymptomatic patients regarding the cytomegalovirus serological
      status. Memory CD8(+) T cells (CCR5(high)CD3(+)CD8(+)), memory/effector cells
      (CD27(+)CD28(-)CD3(+)CD8(+)), effector cells (CD27(-)CD28(-)CD3(+)CD8(+)) and
      activated CD8(+) T cells (CD11b(+)CD3(+)CD8(+)) were identified by flow cytometry
      in peripheral blood of 19 (seven cytomegalovirus (CMV)(+)/12 CMV(-)) patients
      with allergic asthma (AA) and 21 (seven CMV(+)/14 CMV(-)) healthy controls (HC).
      Effector and activated CD8(+) T cells were significantly elevated in CMV(+) HC
      compared to CMV(-) HC. There was a non-significant trend for reduced percentages
      of effector CD8(+) T cells in CMV(+) AA (median: 10.4%, range: 4.4-33.8%)
      compared to CMV(+) HC (median: 23.1%, range: 10.7-54.1%; P = 0.128) and in CMV(-)
      AA (median: 4.1%, range: 0.6-13.4%) compared to CMV(-) HC (median: 5.7%, range:
      0.2-17.0%; P = 0.085). Activated CD8(+) T cells were reduced significantly in
      CMV(+) AA (median: 17.0%, range: 6.0-29.4%) compared to CMV(+) HC (median: 40.4%,
      range: 18.9-67.0%; P = 0.004) and showed a non-significant trend in CMV(-) AA
      (median: 15.0%, range: 2.9-24.0%) compared to CMV(-) HC (median: 20.2%, range:
      5.8-71.0%; P = 0.060). Activated CD8(+) T cells are significantly reduced in
      CMV(+) patients with allergic asthma. Furthermore, a trend for an impaired
      terminal CD8(+) T cell differentiation is observed in CMV(+) and CMV(-) patients
      with asthma.

PMID- 17511781
TI  - Fine needle aspiration cytology from a cystic breast lump.

PMID- 17511782
TI  - Quantitative imaging of apoptosis commitment in colorectal tumor cells.
AB  - We have studied caspase-3 activation by combined DNA damage induction and EGFR
      kinase inhibition in order to identify potential EGFR-mediated survival signals
      conferring resistance to apoptosis in human colorectal tumor cells. The onset of
      apoptosis was microscopically imaged with a newly developed caspase-3 substrate
      sensor based on EGFP and tHcred1, enabling us to monitor caspase-3 activation in
      cells by fluorescence lifetime imaging microscopy or fluorescence correlation
      spectroscopy. Both optical approaches provide parameters quantitatively reporting
      the ratio between cleaved and uncleaved sensor, thereby facilitating the
      comparison of caspase-3 activation between different cells. Using these methods,
      we show that EGFR kinase inhibitors sensitize colorectal SW-480 tumor cells for 5
      fluorouracil-induced apoptosis, indicating that EGFR-mediated survival signaling
      contributes to apoptosis resistance via its intrinsic kinase activity.

PMID- 17511783
TI  - Association of CD14, IL1B, IL6, IL10 and TNFA functional gene polymorphisms with
      symptomatic dental abscesses.
AB  - AIM: To investigate in individuals with symptomatic dental abscesses the
      occurrence of functional polymorphisms within five genes involved with the immune
      response. The functional gene polymorphisms analysed were CD14 (-260 C/T), IL1B
      (+3954 C/T), IL6 (-174 G/C,), IL10 (-1082 G/A) and TNFA (-308 G/A). METHODOLOGY:
      Genomic DNA obtained from oral swabs from individuals with symptomatic dental
      abscesses and asymptomatic inflammatory periapical lesions, without previous
      exacerbation, was submitted to restriction fragment length polymorphism (RFLP)
      analyses to determine each individual genotype. The chi-square and principal
      components analysis tests were used for statistical analysis. RESULTS: A
      significant association was observed between the occurrence of the GG genotype or
      the G allele expression of the polymorphic locus-174 (G/C) of the IL6 gene, and
      the presence of the symptomatic dental abscesses in women and in individuals < or
      =35 years old. The principal components analysis suggested predominance of the
      symptomatic dental abscesses in individuals displaying: high-producer IL6
      genotype; intermediate and high-producer IL1B genotypes and low-producer TNFA
      genotype. CONCLUSIONS: The present study suggests that genetic factors are
      associated with susceptibility to develop symptomatic dental abscesses.

PMID- 17511784
TI  - Comparison of root canal preparation with two rotary NiTi instruments: ProFile
      .04 and GT Rotary.
AB  - AIM: To compare root canal preparation using ProFile .04 and GT Rotary nickel
      titanium instruments (both Dentsply Maillefer, Ballaigues, Switzerland).
      METHODOLOGY: Fifty extracted mandibular molars with mesial root canal curvatures
      between 20 and 40 degrees were randomly divided into two groups and embedded in a
      muffle system. All root canals were prepared to size 45 using ProFile .04 or GT
      rotary instruments. The following parameters were evaluated: straightening of
      root canal curvature, postoperative root canal cross-section, cleaning ability,
      safety issues and working time. RESULTS: Both NiTi systems maintained curvature
      well; the mean degree of straightening was <1 degrees . The majority of the root
      canals prepared with ProFile .04 (80.8%) and GT (84.0%) postoperatively showed a
      round or oval cross-section. For debris, ProFile .04 and GT rotary achieved 67.1%
      and 71.6% scores of 1 and 2, respectively. Concerning the coronal region
      statistical analysis showed a better result for GT than for ProFile .04. For the
      middle and apical thirds of the root canals, results did not differ
      significantly. None of the two systems completely removed smear layer. Ten
      procedural incidents occurred with ProFile .04 compared with five with GT. Mean
      working time was shorter for ProFile .04 (131.8 s) than for GT (143.7 s); the
      difference was not significant. CONCLUSIONS: Both systems respected original root
      canal curvature well and were safe to use. Smear layer removal was not
      satisfactory with either systems.

PMID- 17511786
TI  - Fatigue testing of a NiTi rotary instrument. Part 2: Fractographic analysis.
AB  - AIM: To examine the topographic features of the fracture surface of a NiTi
      instrument after fatigue failure, and to correlate the measurements of some
      features with the cyclic load. METHODOLOGY: A total of 212 ProFile rotary
      instruments were subjected to a rotational-bending test at various curvatures
      until broken. The fracture surface of all fragments was examined by SEM to
      identify the crack origins. The crack radius, i.e. extent of the fatigue-crack
      growth towards the centroid of the cross-section, was also measured, and
      correlated with the strain amplitude for each instrument. RESULTS: All fracture
      surfaces revealed the presence of one or more crack origins, a region occupied by
      microscopic striations, and an area with microscopic dimples. The number of
      specimens showing multiple crack origins was significantly greater in the group
      fatigued under water than in air (P < 0.05). A linear relationship between the
      reciprocal of the square root of the crack radius and the strain amplitude was
      discernible (P < 0.001), the slopes of which were not significantly different for
      instruments fatigued in air and water. CONCLUSIONS: The fractographic appearance
      of NiTi engine-files that had failed because of fatigue is typical of that for
      other metals. The fatigue behaviour of NiTi instruments is adversely affected by
      water, not only for the low-cycle fatigue life, but also the number of crack
      origins. There appears to be a critical extent of crack propagation for various
      strain amplitudes leading to final rupture (akin to the Griffith's criterion for
      brittle materials).

PMID- 17511785
TI  - Differential signalling pathways involved in cholinoceptor-dependent stimulation
      of nitric oxide isoforms in dental pulp.
AB  - AIM: To investigate the role of muscarinic acetylcholine receptor (mAChR) subtype
      activity in the regulation of endothelial- (e) and neuronal- (n) nitric oxide
      synthase (NOS) expression and activity. METHODOLOGY: Rat dental pulp tissue was
      used throughout the study. The e-nos and n-nos mRNA levels were specifically
      measured using reverse transcriptase polymerase chain reaction procedures that
      involve simultaneous co-amplification of both target cDNA and a reference
      template with a single set of primers. NOS activity was measured by the
      production of [U-(14)C]-citrulline from [U-(14)C]-arginine. RESULTS: Stimulation
      of M(1)/M(2) and M(3)/M(4) mAChRs with pilocarpine caused an increase in e-nos
      and n-nos mRNA levels and NOS activity in the dental pulp. The specific mAChR
      subtype antagonists, L-NMMA, l-NIO and N(2)-propyl-L-arginine but not
      aminoguanidine attenuated all these effects. Inhibitors of phospholipase C (PLC),
      protein kinase C (PKC) and calcium/calmodulin (CaM) prevented the pilocarpine
      dependent increase in n-nos and e-nos mRNA levels and NOS activity. CONCLUSIONS:
      Activation of mAChR subtypes stimulated NOS activity by increasing the production
      of NO through e-nos and n-nos gene expression and NOS activity. The mechanism
      appears to occur secondarily to stimulation of CaM and PKC enzymatic activity.

PMID- 17511787
TI  - Effectiveness of two nickel-titanium rotary instruments and a hand file for
      removing gutta-percha in severely curved root canals during retreatment: an ex
      vivo study.
AB  - AIM: To evaluate ex vivo the effectiveness of hand files, ProTaper and R-Endo
      rotary instruments when removing gutta-percha from curved root canals.
      METHODOLOGY: Ninety severely curved teeth were divided into three groups. The
      root canals were accessed, prepared and filled with vertically condensed gutta
      percha and sealer. Removal of gutta-percha was performed with the following
      devices and techniques: Hedstrom files (Vereinigte Dentalwerke, Munich, Germany),
      ProTaper (Dentsply Maillefer, Ballaigues, Switzerland) and R-Endo (Micro-Mega,
      Besancon, France). All techniques were used with the solvent eucalyptol. The
      amount of filling material debris remaining on root canal walls was assessed
      radiographically from two directions: mesio-distal and bucco-lingual. The images
      were digitized and analysed with autocad 2000 software. Total canal area, area of
      the cervical, middle and apical thirds, and area of remaining filling material
      from both directions were outlined by two different operators and calculated.
      Statistical analysis of remaining filling material within each third of the
      canals was performed by the Kruskal-Wallis test. RESULTS: Comparisons of the
      percentages of remaining filling material in the entire canal did not reveal any
      significant differences between the methods of removal. However, the canal third
      was of relevance in all groups; the apical third had the most remaining filling
      material compared with the middle and cervical thirds (P = 0.0012). CONCLUSION:
      All instruments left filling material inside the root canal. ProTaper and R-Endo
      rotary instruments were inadequate for the complete removal of filling material
      from the root canal system.

PMID- 17511788
TI  - Ex vivo microscopic assessment of factors affecting the quality of apical seal
      created by root-end fillings.
AB  - AIM: (i) To evaluate the incidence of microcracks around root-end preparations
      completed with ultrasonic tips and their relationship with the root filling
      technique and thickness of surrounding dentine. (ii) To investigate the effect of
      rapid exposure to a water-soluble dye of Intermediate Restorative Material (IRM),
      Super Ethoxybenzoic Acid (sEBA) and Mineral Trioxide Aggregate (MTA), on the
      marginal adaptation and microleakage of root-end fillings. (iii) To describe the
      microstructure of the surface of root-end filling materials. METHODOLOGY: Ninety
      two single-rooted teeth were divided into two groups (n = 46) according to the
      root canal instrumentation/filling techniques. Group 1 consisted of specimens in
      which canal preparation was completed using a crown-down technique and then
      filled with the Thermafil system (TF group); Group 2 consisted of specimens in
      which canal preparation was completed using a step-back technique and lateral
      condensation (LC group). Following root-end resection and ultrasonic cavity
      preparation, the samples were further divided into three subgroups (n = 24) for
      root-end filling with IRM, sEBA or MTA. The ultrasonic preparation time was
      recorded. Eight teeth were kept as positive and 12 as negative controls.
      Following immersion in Indian ink for 7 days, all resected root surfaces were
      evaluated for the presence of microcracks and the cross-sectional area of root
      end surface and root-end filling were measured to evaluate the thickness of the
      dentinal walls. Thereafter, the samples were sectioned longitudinally so as to
      assess the depth of dye penetration and marginal adaptation of root-end fillings.
      Negative controls longitudinally sectioned were used to describe microstructural
      characteristics of the root-end filling materials using scanning electron
      microscopic (SEM) techniques. RESULTS: Although the thickness of dentinal walls
      between groups 1 and 2 was similar, the ultrasonic preparation time and number of
      microcracks were significantly higher (P < 0.001) in the TF group. Both groups
      had a significant correlation between microcracks and ultrasonic preparation time
      (P < 0.001). sEBA and IRM had better adaptation and less leakage compared with
      MTA. A SEM analysis displayed microstructural differences between the root-end
      filling materials. CONCLUSION: Microcracks can occur independently of the
      thickness of dentinal walls and may be associated with the prolonged ultrasonic
      preparation time required for the removal of the root filling during root-end
      cavity preparation. Although sEBA and IRM had better behaviour than MTA regarding
      microleakage and marginal adaptation, it is possible that exposure of MTA to a
      water-soluble dye before achieving full set and its porous microstructure
      contributed to the results.

PMID- 17511789
TI  - Vasoactive intestinal peptide receptor expression in chronic periapical lesions.
AB  - AIM: To use radioreceptor analysis for evaluating whether vasoactive intestinal
      peptide (VIP) receptors are present in chronic periapical lesions and to
      determine whether differences in its expression are found according to the size
      of the lesions. METHODOLOGY: Twelve periapical lesions were obtained from teeth
      diagnosed with chronic apical periodontitis and indicated for endodontic surgery;
      they were classified according to the size of the lesion in two groups of six
      samples (lesion size greater or smaller than 5 mm), and then processed and
      labelled with (125)I-VIP. Binding sites were identified by (125)I-VIP and
      standard VIP competition assays. Mann-Whitney's test was used to establish
      statistically significant differences in the VIP receptor expression between
      groups. RESULTS: Vasoactive intestinal peptide receptor expression was found in
      all periapical lesion samples. There was a statistically significantly higher
      expression in periapical lesions <5 mm (P < 0.001). CONCLUSION: Vasoactive
      intestinal peptide receptors were expressed in chronic periapical lesions with
      levels inversely proportional to lesion size.

PMID- 17511790
TI  - Radiopacity of root filling materials using digital radiography.
AB  - AIM: To evaluate radiopacity of root filling materials using digital radiography.
      METHODOLOGY: The sealers tested were AH Plus, Endofill, EndoREZ and Epiphany.
      Gutta-percha (Dentsply Maillefer) and Resilon cones were also tested. Acrylic
      plates, containing six wells, measuring 1 mm in depth and 5 mm in diameter, were
      prepared for the test, and filled with the materials. The test samples were
      radiographed together with an aluminium stepwedge calibrated in millimetres,
      according to ANSI/ADA Specification 57. For the radiographic exposures, digital
      imaging plates and an X-ray machine at 70 kVp and 8 mA were used. The object-to
      focus distance was 30 cm, and the exposure time, 0.2 s. After the laser optic
      reading process, the software determined the radiopacity of the standardized
      areas, using grey-scale values, calculating the average radiographic density for
      each material. RESULTS: The decreasing values of radiopacity of the studied
      materials, expressed in millimetres of aluminium equivalent, were: Resilon
      (13.0), AH Plus(TM) (11.2), gutta-percha (9.8), Epiphany (8.0), Endofill (6.9)
      and EndoREZ (6.6). CONCLUSION: All materials had radiopacity values above 3 mm of
      aluminium recommended by ANSI/ADA Specification 57.

PMID- 17511791
TI  - Effect of pioglitazone on the drivers of cardiovascular risk in type 2 diabetes.
AB  - The prevalence of type 2 diabetes and its associated mortality and morbidity are
      continuing to increase across the world. People with type 2 diabetes typically
      have a cluster of risk factors for cardiovascular disease, including
      hyperglycaemia, hypertension and lipid abnormalities, which contribute to the
      high cardiovascular morbidity and mortality in these patients. Targets for
      glycosylated haemoglobin, lipids and blood pressure are becoming more stringent,
      and most patients will require multiple therapies to maximally reduce
      cardiovascular risk. In a large randomised, controlled, long-term cardiovascular
      outcomes study pioglitazone showed durable glycaemic control, a powerful insulin
      sparing effect and changes in the lipid profile associated with reduced
      cardiovascular risk. This article reviews these metabolic findings in the context
      of previous randomised, controlled studies for pioglitazone and discusses whether
      the integration of this agent into the treatment regimen of appropriate patient
      groups has the potential to improve cardiovascular outcomes in type 2 diabetes.

PMID- 17511793
TI  - Higher risk of ischaemic stroke associated with factor XI levels in dyslipidaemic
      patients.
AB  - BACKGROUND: Ischaemic stroke (IS) is a complex disease that involves genetic and
      environmental factors. The role of factor XI (FXI) in arterial thrombosis is
      unclear. We have investigated the risk of IS related to FXI levels in a case
      control study. METHODS: We studied 445 individuals: 218 diagnosed with IS and 227
      age-gender-ethnic matched control subjects. We measured factor VIIIc, fibrinogen
      and factor XIc levels. FXI < 144% was taken as the reference group in the
      statistical analysis. RESULTS: There were 104 women and 114 men in the IS group
      and 108 women and 119 men in the control group. The crude odds ratio (OR) of IS
      in dyslipidaemic patients with high levels of FXI was 4.2 [95% confidence
      interval (CI): 1.2-14.8] compared with dyslipidaemic controls and low levels of
      FXI, but the OR in the non-dyslipidaemic with high levels of FXI subgroup was 1.2
      (95% CI: 0.4-3.2). The adjusted OR of IS in dyslipidaemic patients with high
      levels of FXI was 6.4 (95% CI: 1.6-26.1) compared with dyslipidaemic controls,
      but the OR in non-dyslipidaemic subgroup with high levels of FXI was 0.6 (95% CI:
      0.2-2.1). CONCLUSION: We found almost a sixfold higher risk of IS in patients
      with dyslipidaemia and high levels of FXI. Further studies should elucidate the
      role of FXI in IS and therapeutic approaches should become apparent for patients
      with dyslipidaemia and high-FXI plasma levels.

PMID- 17511792
TI  - Adult-onset Still's disease.
AB  - BACKGROUND: Adult-onset Still's disease (AOSD) is a febrile disorder of unknown
      aetiology characterised by typical spiking fever, evanescent rash, arthralgia and
      leucocytosis. METHODS: According to the diagnostic criteria of AOSD, we
      identified 84 patients between 1990 and 2003. The aim of this study was to
      analyse the characteristics of AOSD in Turkish patients who were followed-up in a
      tertiary referral centre. RESULTS: Of 84 patients of AOSD, 59 (70.2%) were
      female, 25 (29.8%) were male. Arthralgia (96.4%), fever (95.2%), arthritis (69%),
      sore throat (65.5%) and typical rheumatoid rash (59.5%) were the most common
      findings. The mean value of laboratory findings were as follows; C-reactive
      protein level of 11.59 +/- 6.81 mg/dl, erythrocyte sedimentation rate (ESR) of
      89.05 +/- 31 mm/h, leukocyte count of 16,234.51 +/- 7785.2/microl. Leucocytosis
      was present in 69 patients (84.15%). Forty-eight patients had a WBC count >or=
      15,000/microl. Hypoalbuminaemia was present in 35 patients. Abnormal levels of
      aspartate aminotransferase and alanine aminotransferase were observed in 30
      patients, whereas abnormal levels of alkaline phosphatase in 16 patients. Thirty
      seven patients had an ESR value of more than 100 mm/h. Thirty-two patients had a
      ferritin value of more than 1000 ng/dl. CONCLUSION: High fever, sore throat,
      rheumatoid rash, polyarthritis, hyperferritinaemia (>or= 1000 ng/ml),
      leucocytosis with a neutrophilic predominance, anaemia and hypoalbuminaemia were
      remarkable observations in the initial examination.

PMID- 17511794
TI  - Association of left ventricular diastolic function abnormalities with aortic
      elastic properties in asymptomatic patients with type 2 diabetes mellitus. A
      tissue doppler echocardiographic study.
AB  - BACKGROUND: The aim of this study was to investigate the association between the
      aortic elastic properties and the left ventricular diastolic function measured by
      tissue Doppler echocardiography (TDE) in asymptomatic type 2 diabetes mellitus.
      METHODS: Fifty-seven asymptomatic patients with type 2 diabetes (33 women, mean
      age: 49 +/- 6 years) and 25 healthy control subjects (19 women, mean age: 46 +/-
      7 years) were included in the present study. Diastolic filling indices were
      measured by conventional (CE) and tissue Doppler echocardiography. The aortic
      elastic properties [Aortic stiffness index (ASI), aortic distensibility and
      strain] were measured as previous definition. RESULTS: Compared with control
      subjects, the ratio of LV diastolic abnormalities measured by CE and TDE were
      found higher in patients with type 2 diabetes (36% and 73.6%, p = 0.001,
      respectively, and 52% and 89.4%, p < 0.001, for septal annulus; 48% and 89.4%, p
      < 0.001 for septal basal respectively). The ASI was significantly higher (p <
      0.001), aortic distensibility and aortic strain were also significantly lower in
      patients with type 2 diabetes than control subjects (p < 0.001 and p < 0.001
      respectively). In the regression analysis, Ao distensibility was correlated to
      age (beta = -0.299, p = 0.004), septal basal Em/Am ratio (beta =0.543, p < 0.001)
      and HDL-cholesterol (beta = 0.192, p = 0.039). ASI was also correlated only to
      age (beta = 0.255, p = 0.044), the presence of diabetes mellitus (beta = 0.304, p
      = 0.009), mitral A wave (beta = 0.322, p = 0.013) and mitral annulus Em wave
      (beta = -0.505, p < 0.001). CONCLUSION: The aortic elastic function is impaired
      in asymptomatic patients with type 2 diabetes. Increased ASI and decreased Ao
      distensibility are closely associated with diastolic filling indices measured by
      CE and TDE.

PMID- 17511795
TI  - Issues in the pharmacological treatment of obsessive-compulsive disorder.
AB  - AIMS: Obsessive-compulsive disorder (OCD) preferentially responds to a class of
      antidepressants called serotonin reuptake inhibitors (SRI). This review discusses
      certain issues unique to pharmacological treatment of OCD: choice of SRI, dose
      and duration of treatment, options after first failed SRI trial and treatment of
      SRI non-responders. METHODS: We performed a MEDLINE search for pharmacotherapy
      studies published until December 2006. In addition, the reference sections of
      major articles, and reviews were also screened. We also considered clinical
      guidelines and narrative reviews in writing this review. RESULTS: The SRIs are
      equally effective in treating OCD. Meta-analyses suggest that clomipramine may be
      superior to other SRIs. OCD tends to respond to higher doses of SRIs than that
      used to treat depression. Response to treatment is usually delayed and may take
      up to 8-12 weeks. Atypical antipsychotics are the only proven augmenting agents
      in SRI non-responders. Cognitive behaviour therapy (CBT) is an effective
      treatment strategy in treating OCD and possibly has a role in treating SRI non
      responders. DISCUSSION: Side effect profile and drug-drug interactions largely
      determine the choice of SRI. Those who fail to respond to one SRI trial may well
      respond to another SRI trial. Clomipramine is recommended if 2-3 trials of SRIs
      fail to produce response. Atypical antipsychotics are the first-line augmenting
      agents in SRI non-responders. CBT should be considered in all patients with OCD
      and is a potential option in SRI non-responders. CONCLUSION: OCD is a chronic and
      debilitating disorder. In responders, SRIs have to be continued in the same doses
      (if possible) for a minimum of 1-2 years and may be lifelong in those with
      persistent symptoms and in those with multiple relapses. CBT has to be offered in
      combination with SRIs wherever facilities for CBT exist.

PMID- 17511796
TI  - Peripheral primitive neuroectodermal tumour of the pleura: case report and
      literature review.

PMID- 17511797
TI  - Effectiveness of oral and intravenous iron therapy in haemodialysis patients.
AB  - Anaemia is a common and serious complication in patients with end-stage renal
      disease. Iron therapy is crucial in managing anaemia and maintenance of
      haemodialysis (HD) patients. This study investigated the efficacy of both oral
      and intravenous (i.v.) therapies, and the possible factors deleteriously
      affecting patient response to iron therapy. Forty patients on maintenance HD from
      a single institution were enrolled in this 6-month retrospective study. Group I
      (n = 20) received i.v. two ampoules of atofen (ferric chloride hexahydrate 193.6
      mg) per week for a total of 6 weeks (total dosage, 960 mg). Group II (n = 20)
      received oral ferrous sulphate S.C. Tab (ferrous sulphate 324 mg) one pill three
      times daily (total dosage, 63,000 mg). Patients whose haematocrit (Hct) level
      increased at minimum 3% within the period were classified as responders. Iron
      i.v. ferric chloride (960 mg) was more effective than oral ferrous sulphate
      (63,000 mg) in correcting anaemia in HD patients with iron deficiency. In group
      I, serum triglyceride (TG) levels were significantly lower in patients responding
      to i.v. iron therapy than in patients with no response. In group II, serum high
      sensitive C-reactive protein (hs-CRP) level was significantly lower in patients
      responding to oral iron therapy than patients with no response. The i.v. ferric
      chloride is more effective than oral ferrous sulphate in treating anaemia in HD
      patients with iron deficiency. Serum hs-CRP and TG levels may be parameters for
      predicting hyporesponsiveness to oral and i.v. iron therapies, respectively.

PMID- 17511798
TI  - Weekly cisplatin with oral etoposide: a well-tolerated and highly effective
      regimen in relapsed ovarian cancer.
AB  - The optimal treatment of progressive ovarian cancer after first-line platinum
      based therapy remains a challenge. We collected prospectively data on patients
      with relapsed or progressive ovarian cancer treated with weekly cisplatin and
      oral etoposide in our institution to evaluate the feasibility, efficacy, and
      toxicity of this regimen. Patients (n = 34) had stage IIIC/IV ovarian cancer,
      which was recurrent or progressive following previous treatment with carboplatin
      and a taxane. Cisplatin (50 mg/m(2)) was given days 1, 8, 15, 29, 36, and 43,
      with oral etoposide (50 mg daily) on days 1-15 and 29-43. Responders and those
      with stable disease then received oral etoposide (50 mg daily for 21 days of a 28
      day cycle) until disease progression. The overall CA125 response rate was 88%.
      The overall radiological response rate was 57%: 78% in the platinum-sensitive
      group, 50% in the intermediate-sensitive group, and 46% in the platinum-resistant
      group. Treatment was well tolerated. Median survival in the overall group was 14
      months: in the platinum-sensitive group 16.5 months, in the intermediate
      sensitive group 11 months, and 10.5 months in the platinum-resistant group. We
      conclude that weekly cisplatin/etoposide, followed by maintenance oral etoposide,
      is an active and well-tolerated regimen in relapsed or progressive ovarian
      cancer, even in platinum-resistant patients.

PMID- 17511799
TI  - Early identification of persistent trophoblastic disease with serum hCG
      concentration ratios.
AB  - The objective of the present study was to assess the diagnostic potential of
      serum human chorionic gonadotropin (hCG) ratios obtained at different intervals
      after evacuation of hydatidiform mole to diagnose persistent trophoblastic
      disease (PTD) and to compare its diagnostic accuracy with the current FIGO 2000
      criteria as a gold standard. We calculated hCG ratios from serum hCG
      concentrations of 204 patients (86 with and 118 without PTD) registered with the
      Dutch Central Registry for Hydatidiform Moles between 1977-2004. The hCG ratios
      obtained in week 1, 3, and 5 after evacuation identified, respectively, 20%, 52%,
      and 79% of patients with PTD (median: 3.0 weeks) at the 95% specificity level,
      while FIGO 2000 criteria identified, respectively, 0%, 16%, and 66% (median: 4.7
      weeks). It is concluded that a serum hCG ratio identifies patients with PTD
      approximately 2 weeks earlier than the internationally accepted FIGO 2000
      criteria and identifies more than 75% of patients who develop PTD by the fifth
      week after evacuation.

PMID- 17511800
TI  - Cardiac safety profile of pegylated liposomal doxorubicin reaching or exceeding
      lifetime cumulative doses of 550 mg/m2 in patients with recurrent ovarian and
      peritoneal cancer.
AB  - The objective of this study is to evaluate the cardiac safety of pegylated
      liposomal doxorubicin (PLD) reaching or exceeding a cumulative dose of 550
      mg/m(2) in patients with recurrent ovarian and peritoneal cancer. A total of 14
      patients (11 ovarian cancer, 3 primary peritoneal cancer) who received PLD in our
      center between February 2004 and October 2006 met inclusion criteria of the
      study. PLD was administered at doses of 30 mg/m(2) together with carboplatin or
      50 mg/m(2) as a single agent every 3-6 weeks. Left ventricular ejection fraction
      (LVEF) estimations performed by M Mode ultrasound (General Electric Vivid-3,
      Milwaukee, Wisconsin) and clinical cardiac status were used to detect PLD-related
      cardiotoxicity. The median cumulative dose of PLD was 685.5 mg/m(2) (range 552
      1015 mg/m(2)) and the median number of PLD courses was 9.5 (range 7-17). One
      patient had also been previously treated with conventional doxorubicin. LVEF
      scans were obtained on 10 of the 14 patients at the beginning of the therapy and
      on all patients at the end of therapy. No clinical evidence (symptoms or physical
      findings) of cardiac dysfunction had been observed in these patients either
      during active treatment or follow-up period. Despite small number of patients and
      lack of control group, our study suggests that the cumulative doses in excess of
      550 mg/m(2) of PLD seem to not carry a significant risk of cardiomyopathy as
      judged by LVEF and clinical follow-up.

PMID- 17511801
TI  - Influences on multidisciplinary team decision-making.
AB  - The objective is to explore how clinical decisions are made in a cancer
      multidisciplinary team meeting (MDM). The study design is qualitative based on
      participant observation, in depth interviews, and questionnaires. The research
      setting was weekly cancer MDM which provides a forum for clinical debate for
      practitioners in the field of women's health, working within one Cancer Network
      in England. The participants were 53 practitioners attending a weekly MDM over a
      4-month period. Analysis of nonparticipant observation data and practitioner
      interview narratives identified key influences on the work of the MDM, and in
      particular decision-making. The research identified three major influences on the
      conduct of the MDM. First, MDM discussions are dominated by those with surgical,
      medical, or diagnostic expertise with limited contributions from those with a
      nursing, palliative, or psychosocial background. Second, decision-making is
      shaped by an overriding need to comply with policy initiatives concerning the
      organization of diagnosis and treatment. The third influence is whether the
      patient is known or unknown to some degree by members of the MDM. Where there is
      preexisting knowledge of the patient, the discussion and decision is inclusive of
      a wider range of disciplines. Team working in these circumstances is an
      acknowledged source of satisfaction and motivation. Where the patient is not
      known, discussion concerns only the physical details necessary to make a
      diagnosis and contributions from the wider team (including those with knowledge
      of psychosocial care) are rare. Practitioners' sphere of expertise, Department of
      Health policy, and familiarity of the team with the patient are key factors in
      shaping decision-making in MDMs.

PMID- 17511802
TI  - Decreased dose density of standard chemotherapy does not compromise survival for
      ovarian cancer patients.
AB  - For women diagnosed with ovarian cancer, the standard practice of surgery
      followed by adjuvant platinum-taxane combination chemotherapy, with cycles
      administered every 3 weeks, is based on randomized control trials. However, a
      substantial number of patients require delays or reductions on this schedule. The
      Cancer Centre of Southeastern Ontario (CCSEO) has historically administered
      chemotherapy every 4 weeks. We analyzed survival outcomes of our cohort. All
      ovarian cancer patients treated with chemotherapy at the CCSEO from 1995 to end
      2002 were included in this study. Overall survival and progression-free survival
      were calculated from initiation of chemotherapy using the Kaplan-Meier technique
      and log-rank tests. Cox regression analysis was used to adjust for age and
      disease stage. A total of 171 patients were treated with chemotherapy (cisplatin
      paclitaxel or carboplatin-paclitaxel), of which 144 received chemotherapy every 4
      weeks and 27 every 3 weeks. Median progression-free survival was 19.2 months for
      the group treated every 4 weeks vs 13.2 months for the 3-weekly group. Median
      overall survival was 36.5 months compared to 27.1 months, respectively. Trends
      favored treatment every 4 weeks. In early-stage disease, 5-year overall survival
      was 74% and 5-year progression-free survival was 68%. Administration of platinum
      paclitaxel chemotherapy every 4 weeks did not reduce survival of ovarian cancer
      patients. Importantly, median survival is favorable compared to results from
      landmark trials where patients were treated every 3 weeks. These results suggest
      that decreasing the frequency of chemotherapy cycles does not decrease survival.
      Prospective trials would be required to compare quality of life and cost
      effectiveness.

PMID- 17511803
TI  - Epstein-Barr virus-associated smooth muscle tumor presenting as a vulvar mass in
      an acquired immunodeficiency syndrome patient: a case report.
AB  - Smooth muscle tumors in immunocompromised patients have a strong association with
      Epstein-Barr virus (EBV) infection. EBV-associated smooth muscle tumors (EBV-SMT)
      are considered as a distinct group of smooth muscle tumors with different
      clinicopathologic features from conventional smooth muscle tumors. A 31-year-old
      female patient presented with a 2-cm mass at the left labium majus, the clinical
      diagnosis of which was a Bartholin lesion. She had acquired immunodeficiency
      syndrome diagnosed 29 months before. Excisional biopsy revealed a cellular tumor
      composed of round- to spindle-shaped cells with mild to moderate nuclear atypia.
      The tumor cells were immunoreactive for smooth muscle actin and muscle actin (HHF
      35). Evidence of EBV infection was confirmed by in situ hybridization for EBV
      encoded small RNA-1. To our knowledge, this is the first case of EBV-SMT
      presenting as a vulvar mass. EBV-SMT should be included in the differential
      diagnoses of mesenchymal tumor in patients with immunosuppression and in the
      differential diagnoses of smooth muscle tumor in uncommon sites, including the
      vulva.

PMID- 17511805
TI  - Intraplacental choriocarcinoma as an unexpected cause of intrauterine death at
      term.
AB  - Intraplacental choriocarcinoma is rare. It can cause fetal death at term by
      fetomaternal hemorrhage. We present a case of intraplacental choriocarcinoma.
      After a hydatidiform mole with persistence of throphoblastic disease, the patient
      delivered a stillborn baby at term. Massive fetomaternal hemorrhage was the
      unexpected cause of death. Choriocarcinoma was only diagnosed after pathologic
      revision of the placenta because of persistent high levels of serum hCG (human
      chorionic gonadotropin). Massive fetomaternal hemorrhage should alert the
      obstetrician and the pathologist to the possibility of choriocarcinoma arising
      from the placenta.

PMID- 17511804
TI  - Mucinous ovarian tumors associated with pseudomyxoma peritonei of adenomucinosis
      type: immunohistochemical evidence that they are secondary tumors.
AB  - Pseudomyxoma peritonei (PMP) is a clinical condition initially thought to be
      related to ovarian mucinous tumors; however, immunohistochemistry and molecular
      biology techniques have convincingly made the link to appendiceal mucinous
      neoplasms, resulting in changes in histologic and clinical approaches. The
      objective of this study was to compare the immunohistochemical profile of ovarian
      tumors associated with PMP and intestinal mucinous ovarian neoplasms without PMP.
      The study was retrospective and included 28 intestinal ovarian mucinous tumors
      selected from the files of the Division of Surgical Pathology of the University
      of Sao Paulo Medical School, from 1996 to 2005. Seven cases were associated with
      PMP of disseminated peritoneal adenomucinosis-type and all presented borderline
      histology. Immunohistochemical staining for mucin genes products (MUC1, MUC2,
      MUC5AC, and MUC6), CK7, CK20, CA19.9, and CA125 were performed in tissue
      microarrays. Of note, we detected differences in the expression of MUC2 and CK20
      between cases with and without PMP. Comparisons of borderline histology with that
      of benign/malignant tumors also revealed differences in MUC2 and CK20. Our
      results confirm that there is a distinct profile of intestinal ovarian tumors
      associated with pseudomyxoma, particularly with respect to the expression of the
      gel-forming mucin MUC2. The profile of borderline tumors, even in cases without
      PMP, was distinct from that of other primary mucinous tumors of the intestinal
      type, suggesting that borderline histology may represent a secondary tumor or a
      less aggressive variant of PMP. An appendiceal origin seems the most probable for
      this group of neoplasias.

PMID- 17511806
TI  - Residents' perspectives on surgical training and the resident-fellow
      relationship: comparing residency programs with and without gynecological
      oncology fellowships.
AB  - The effect of a gynecological oncology fellow on obstetrics and gynecology
      resident education and training is uncertain. The objective is to assess the
      effect of gynecological oncology fellows on the surgical training of residents in
      obstetrics and gynecology. Fourth year residents in obstetrics and gynecology in
      the United States were identified and stratified as to the presence or absence of
      an oncology fellowship program. Demographics, surgical volume, procedures
      performed, and self-assessment of surgical proficiency were collected. Responses
      were compared between residency programs with and without fellowships. Responses
      were received from 40% of programs. Residents at programs without a fellowship
      more frequently operated with attendings than did residents at programs with
      fellows, 91% vs 77%, P= 0.016, and more frequently were responsible for
      complicated cases, 39% vs 22%, P < 0.0001. Over 90% of residents in both groups
      reported surgical training as positive and valuable; both groups reported a
      similar perceived lack of proficiency in radical hysterectomy and
      lymphadenectomy. Attitudes toward the fellows were generally positive; however,
      competition for cancer cases was reported by over 66% of residents from programs
      with fellows. While fellows are often thought of as a detracting factor to
      residency training, they do not appear to affect the perception of the quality of
      resident surgical training.

PMID- 17511807
TI  - Multimodal therapy for the initial management of genital embryonal
      rhabdomyosarcoma in childhood.
AB  - Rhabdomyosarcoma is the most common soft tissue sarcoma found in children. A
      polypoid form of the embryonal type of rhabdomyosarcoma, namely, sarcoma
      botryoides, is often found in girls younger than 5 years, and typically presents
      as a polypoid mass protruding from the vagina. Over the years, there has been a
      shift in the treatment of this condition from radical surgery to a multimodal
      approach involving conservative surgery with chemotherapy and radiotherapy. This
      approach has been associated with improved survival and preservation of normal
      anatomy and function. We discuss the initial management of a 4-year-old girl with
      pelvic embryonal rhabdomyosarcoma using a multimodal approach.

PMID- 17511808
TI  - Cytokine-mediated control of lipopolysaccharide-induced activation of small
      intestinal epithelial cells.
AB  - Cytokines with anti-inflammatory properties have been implicated in the
      prevention of inappropriate immune activation by commensal bacteria in the
      intestinal tract. Here, we analysed receptor expression, cellular signalling, and
      the inhibitory activity of interleukin (IL)-4, -10, -11, and -13 as well as of
      transforming growth factor-beta on lipopolysaccharide-mediated small intestinal
      epithelial cell activation. Only IL-4 and IL-13 had a significant inhibitory
      effect on chemokine secretion and nitric oxide (NO) production in differentiated
      and polarized cells. Reverse transcription-polymerase chain reaction of primary
      intestinal epithelial cells obtained by laser-microdissection confirmed
      expression of the type II IL-4 receptor consisting of the IL-4 receptor alpha and
      the IL-13 receptor alpha1. Also, IL-4 or IL-13 led to rapid signal transducer and
      activator of transcription 6 phosphorylation, diminished inducible NO synthase
      expression, and enhanced the antagonistic arginase 1 activity. In conclusion,
      cytokines such as IL-4 and IL-13 affect intestinal epithelial cells and exhibit a
      modulating activity on Toll-like receptor-4-mediated epithelial cell activation.

PMID- 17511809
TI  - FtsK, a literate chromosome segregation machine.
AB  - The study of chromosome segregation in bacteria has gained strong insights from
      the use of cytology techniques. A global view of chromosome choreography during
      the cell cycle is emerging, highlighting as a next challenge the description of
      the molecular mechanisms and factors involved. Here, we review one of such
      factor, the FtsK DNA translocase. FtsK couples segregation of the chromosome
      terminus, the ter region, with cell division. It is a powerful and fast
      translocase that reads chromosome polarity to find the end, thereby sorting
      sister ter regions on either side of the division septum, and activating the last
      steps of segregation. Recent data have revealed the structure of the FtsK motor,
      how translocation is oriented by specific DNA motifs, termed KOPS, and suggests
      novel mechanisms for translocation and sensing chromosome polarity.

PMID- 17511810
TI  - An acetylase with relaxed specificity catalyses protein N-terminal acetylation in
      Sulfolobus solfataricus.
AB  - N-terminal protein acetylation is common in eukaryotes and halophilic archaea,
      but very rare in bacteria. We demonstrate that some of the most abundant proteins
      present in the crenarchaeote Sulfolobus solfataricus, including subunits of the
      thermosome, proteosome and ribosome, are acetylated at the N-terminus.
      Modification was observed at the N-terminal residues serine, alanine, threonine
      and methionine-glutamate. A conserved archaeal protein, ssArd1, was cloned and
      expressed in Escherichia coli, and shown to acetylate the same N-terminal
      sequences in vitro. The specific activity of ssArd1 is sensitive to protein
      structure in addition to sequence context. The crenarchaeota and euryarchaeota
      apparently differ in respect of the frequency of acetylation of Met-Glu termini,
      which appears much more common in S. solfataricus. This sequence is acetylated by
      the related Nat3 acetylase in eukarya. ssArd1 thus has a relaxed sequence
      specificity compared with the eukaryotic N-acetyl transferases, and may represent
      an ancestral form of the enzyme. This represents another example where archaeal
      molecular biology resembles that in eukaryotes rather than bacteria.

PMID- 17511811
TI  - Structural asymmetry and discrete nucleic acid subdomains in the Trypanosoma
      brucei kinetoplast.
AB  - The mitochondrial genome of Trypanosoma brucei is contained in a specialized
      structure termed the kinetoplast. Kinetoplast DNA (kDNA) is organized into a
      concatenated network of mini and maxicircles, positioned at the base of the
      flagellum, to which it is physically attached. Here we have used electron
      microscope cytochemistry to determine structural and functional domains involved
      in replication and segregation of the kinetoplast. We identified two distinct
      subdomains within the kinetoflagellar zone (KFZ) and show that the unilateral
      filaments are composed of distinct inner and outer filaments. Ethanolic
      phosphotungstic acid (E-PTA) and EDTA regressive staining indicate that basic
      proteins and DNA are major constituents of the inner unilateral filaments
      adjoining the kDNA disc. This evidence for an intimate connection of the
      unilateral filaments in the KFZ with DNA provides support for models of
      minicircle replication involving vectorial export of free minicircles into the
      KFZ. Unexpectedly however, detection of DNA in the KFZ throughout the cell cycle
      suggests that other processes involving kDNA occur in this domain. We also
      describe a hitherto unrecognized, intramitochondrial, filamentous structure rich
      in basic proteins that links the kDNA discs during their segregation and is
      maintained between them for an extended period of the cell cycle.

PMID- 17511813
TI  - Ectopic expression of a recessive resistance gene generates dominant potyvirus
      resistance in plants.
AB  - Despite long-standing plant breeding investments and early successes in genetic
      engineering, plant viral pathogens still cause major losses in agriculture
      worldwide.Early transgenic approaches involved the expression of pathogen-derived
      sequences that provided limited protection against relatively narrow ranges of
      viral pathotypes. In contrast,this study demonstrates that the ectopic expression
      of pvr1, a recessive gene from Capsicum chinense, results in dominant broad
      spectrum potyvirus resistance in transgenic tomato plants (Solanum lycopersicum).
      The pvr1 locus in pepper encodes the eukaryotic translation initiation factor
      eIF4E. Naturally occurring point mutations at this locus result in monogenic
      recessive broad-spectrum potyvirus resistance that has been globally deployed via
      plant breeding programmes for more than 50 years. Transgenic tomato progenies
      that over-expressed the Capsicum pvr1 allele showed dominant resistance to
      several tobacco etch virus strains and other potyviruses, including pepper mottle
      virus, a range of protection similar to that observed in pepper homozygous for
      the pvr1 allele.

PMID- 17511812
TI  - Identification and characterization of the immunity repressor (ImmR) that
      controls the mobile genetic element ICEBs1 of Bacillus subtilis.
AB  - ICEBs1 is a mobile genetic element found in the chromosome of Bacillus subtilis.
      Excision and transfer of ICEBs1 is regulated by the global DNA damage response
      and intercellular peptide signalling. We identified and characterized a
      repressor, ImmR (formerly YdcN), encoded by ICEBs1. ImmR represses transcription
      of genes required for excision and transfer, and both activates and represses its
      own transcription. ImmR regulates transcription within ICEBs1 by binding to
      several sites in the region of DNA that contains promoters for both immR and xis
      (encoding excisionase). In addition, we found that ImmR confers immunity from
      acquisition of additional copies of ICEBs1. ImmR-mediated regulation serves to
      keep a single copy of ICEBs1 stably maintained in the absence of induction,
      allows a rapid response to inducing signals, and helps limit acquisition of
      additional copies of ICEBs1.

PMID- 17511814
TI  - Surveillance of cytomegalovirus (CMV) DNAemia in pediatric allogeneic stem cell
      transplantation: incidence and outcome of CMV infection and disease.
AB  - Cytomegalovirus (CMV) remains a serious problem after hematopoietic stem cell
      transplantation (HSCT). To investigate the incidence of CMV infection and outcome
      we retrospectively analyzed 70 consecutive pediatric allogeneic HSCTs monitored
      by CMV polymerase chain reaction (PCR), with at least 1-year follow-up or until
      death. All patients at risk for CMV infection (CMV-seropositive patients and CMV
      seronegative recipients transplanted from CMV-seropositive donors) received
      hyperimmune anti-CMV globulins whereas in the group of HSCT patients with both
      donor and recipient CMV negativity, polyvalent immunoglobulins were given, both
      at a dose of 400 mg/kg. All patients received acyclovir at prophylactic doses for
      at least 6 months. Patients were monitored twice a week by CMV PCR. Patients with
      2 positive results for CMV DNAemia received ganciclovir for 14 days and continued
      until 2 consecutive negative results were obtained. The incidence of CMV DNAemia
      was 12.8% (9/70) in the whole group, with significant higher risk for patients
      with CMV-seropositive recipient status, 8 out of 22 (36%), vs. patients with
      seronegative status, 1 out of 48 (2%) (P=0.0002). Three out of 9 patients with
      DNAemia developed CMV disease despite adequate preemptive treatment. The
      transplant-related mortality was higher in the CMV-seropositive recipient group
      (P=0.05). Age, use of hyperimmune anti-CMV globulins at a high dose, and the low
      incidence of graft-versus-host disease might be contributing factors to this low
      incidence.

PMID- 17511815
TI  - Clinical features and outcomes of cytomegalovirus retinitis after
      transplantation.
AB  - Cytomegalovirus (CMV) infection of the retina is a rarely encountered end-organ
      disease after transplantation. In order to describe the clinical characteristics
      and outcomes of CMV retinitis after hematopoietic stem cell and solid organ
      transplantation, we performed a retrospective review of all cases of CMV
      retinitis at the Mayo Clinic (Rochester, Minnesota) during 1990-2004. During this
      15-year period, CMV retinitis was diagnosed in 14 eyes of 9 patients who had
      received kidney (n=5), liver (n=2), heart (n=1), and autologous hematopoietic
      stem cell transplant (n=1). The mean age of the patients was 58 (standard
      deviation+/-11) years; 6 were male. The median time to diagnosis of CMV retinitis
      was 9 months (range, 4 months to 13 years) after transplantation. Four (44%)
      patients had concomitant pneumonitis or hepatitis. Five (55%) patients had
      bilateral retinitis. Retinal involvement was <or=10% in 8 eyes, >10% but <or=50%
      in 4 eyes, and >50% in 2 eyes. All patients received induction therapy with
      intravenous ganciclovir (n=8) or foscarnet (n=1) for a median of 43 days (range,
      14-100 days) followed by maintenance therapy with intravenous or oral ganciclovir
      for a median of 88 days (range, 36-943 days) in 6 (67%) patients. One patient
      developed bilateral immune recovery uveitis during treatment, and later on
      progressed to develop rhegmatogenous retinal detachment. During the mean follow
      up period of 20 months, visual acuity improved in 4 (28.5%), was stable in 4
      (28.5%), and worsened in 6 (43%) eyes. CMV retinitis recurred in 2 patients. In
      conclusion, CMV retinitis is a rare, progressive, and highly morbid infectious
      complication of transplantation. The severity of clinical disease at the time of
      diagnosis may predict poor outcome. Hence, early intervention may be crucial to
      prevent its progression to irreversible visual loss.

PMID- 17511816
TI  - Candida krusei--a serious complication in patients with hematological
      malignancies: successful treatment with caspofungin.
AB  - Candida krusei infections are serious complications in neutropenic patients with
      hematological malignancies. We report the successful treatment of C. krusei
      infection with caspofungin in 3 allogeneic hematopoietic stem cell transplant
      recipients and 1 patient with induction chemotherapy for acute myeloid leukemia.

PMID- 17511817
TI  - Etiologic agents of diarrhea in solid organ recipients.
AB  - After transplantation, diarrhea may be caused by infectious agents, drug-specific
      effects, metabolic conditions, or mechanical complications of surgery.
      Determining the cause helps to determine whether to initiate antimicrobial
      therapy and the duration of treatment. In this study we aimed to determine the
      causes of diarrhea in kidney or liver recipients. Fifty-two diarrhea episodes
      among 43 solid organ recipients were evaluated. The cause of diarrhea was
      detected in 43 patients (82.6%). Infectious etiologies accounted for 33 out of
      the 43 episodes (76.7%) in which a specific cause was determined: Giardia lamblia
      in 9, Cryptosporidium parvum in 7, cytomegalovirus (CMV) in 6, Clostridium
      difficile in 3, Campylobacter jejuni in 2, Shigella sonnei in 2, Salmonella
      enteritidis in 1, rotavirus in 1, Entamoeba histolytica in 1, and Blastocystis
      hominis in 1. Non-infectious etiologies were found for 10 episodes (23.3%):
      mycophenolate mofetil-associated diarrhea in 5, antibiotic-associated diarrhea in
      2, colchicine-associated diarrhea in 2, and laxative drug-associated in 1. Non
      infectious etiologies seem to be relatively common causes of diarrhea among
      transplant recipients. Therapy was adjusted in 5 patients because of
      mycophenolate mofetil-associated diarrhea. CMV and C. parvum, which are seldom
      seen in the normal population, were frequent causes of diarrhea in this group.
      Evaluating the transplant recipients for non-infectious causes of diarrhea is
      important in prompt diagnosis and treatment.

PMID- 17511818
TI  - Airway infection in stable lung transplant patients is associated with decreased
      intracellular T-helper type 1 pro-inflammatory cytokines in bronchoalveolar
      lavage T-cell subsets.
AB  - Current immunosuppression protocols to prevent lung transplant rejection reduce
      pro-inflammatory and T-helper type 1 (Th1) cytokines. However, Th1 T-cell pro
      inflammatory cytokine production is important in host defense against bacterial
      infection in the lungs. Excessive immunosuppression of Th1 T-cell pro
      inflammatory cytokines leaves patients susceptible to infection. To investigate
      whether pulmonary infection in lung transplant recipients is associated with
      reduced Th1 T-cell pro-inflammatory cytokines, whole blood and bronchoalveolar
      lavage (BAL) fluid from 13 stable lung transplant patients with 'culture
      negative' BAL and 13 patients with 'culture-positive' BAL was stimulated in
      vitro, and cytokine production by CD8+ and CD4+ T-cell subsets was determined
      using multiparameter flow cytometry. In BAL samples, there was a significant
      decrease in interleukin-2 (IL2) in CD3+ T cells and tumor necrosis factor-alpha
      (TNF-alpha) in CD8+ T cells (but not CD4+) in 'culture-positive' compared with
      'culture-negative' transplant patients. There was no difference in blood Th1 T
      cell cytokines between 'culture-positive' compared with 'culture-negative'
      transplant patients. A decrease in Th1 cytokines IL-2 and TNF-alpha in BAL T-cell
      subsets is associated with isolation of potentially pathogenic organisms in the
      lungs in stable lung transplant patients. Excessive immunosuppression of these
      Th1 T-cell pro-inflammatory cytokines in stable transplant patients may leave
      them susceptible to infection. Modifying immunosuppression by monitoring
      intracellular Th1 pro-inflammatory cytokines in BAL T cells may help to improve
      morbidity and infection rates in stable lung transplant patients.

PMID- 17511819
TI  - Predictors for persistent cytomegalovirus reactivation after T-cell-depleted
      allogeneic hematopoietic stem cell transplantation.
AB  - Cytomegalovirus (CMV) reactivation occurs in up to 60% of CMV-seropositive
      recipients after allogeneic hematopoietic stem cell transplantation (HSCT). The
      incidence of CMV disease among T-cell-depleted HSCT patients has been reported
      from 5-15%. The incidence of reactivation refractory to antivirals in this
      population is not well studied. METHODS: In this retrospective study we
      characterized the outcome of CMV reactivation in a cohort of 255 adult and
      pediatric patients who underwent T-cell-depleted HSCT at Memorial Sloan-Kettering
      Cancer Center from September 1999 through August 2004. CMV infection was
      monitored by the pp65 antigenemia assay (CMV Ag). Persistent reactivation was
      defined as antigenemia positivity >21 days on antiviral therapy. RESULTS: Of 118
      CMV-seropositive recipients, 69 (58.4%) had reactivated CMV. Twenty of 69 (29%)
      developed persistent reactivation at first episode of reactivation, and 7 (10%)
      in subsequent episode. All patients with persistent reactivation received >/=2
      antivirals and CMV hyperimmune globulin; 45% received combination antiviral
      therapy. The median duration of persistent reactivation was 98 days, range 31-256
      days. In multivariate analysis, maximum CMV Ag >25 cells/slide was associated
      with persistent reactivation (odds ratio 16.2%, 95% confidence interval 4-64,
      P<0.0001). CMV disease occurred in 6/27 (22%) patients with persistent
      reactivation. Patients with persistent reactivation had lower CD4(+) and CD8(+)
      lymphocyte counts compared with those with non-persistent reactivation at day +90
      post HSCT (P=0.01 and 0.02, respectively). CONCLUSIONS: Persistent reactivation
      occurred in 39% of T-cell-depleted HSCT despite treatment with currently
      available antivirals. Maximum CMV Ag >25 cells/slide was associated with
      persistent CMV reactivation. More effective treatment modalities are needed for
      this high-risk population to reduce CMV-associated morbidity and mortality.

PMID- 17511820
TI  - Pulmonary lymphomatoid granulomatosis in a renal allograft recipient.
AB  - Lymphomatoid granulomatosis (LYG) is a rare multisystemic angiocentric
      lymphoproliferative disease, which can masquerade as necrotic tissue. There is a
      paucity of reports of LYG in renal transplant recipients. Herein, we describe LYG
      in a 56-year-old renal allograft recipient 11 years after transplantation, on
      azathioprine and prednisolone maintenance immunosuppression, presenting to us
      with fever, weight loss, and nodular and patchy opacities in both lung fields.
      Initial percutaneous samples showed necrotic tissue while open biopsy revealed
      characteristic histopathology with evidence of Epstein-Barr virus. We have
      reviewed the radiological and pathological findings, and discussed clinical
      features, differential diagnosis, and treatment of LYG.

PMID- 17511821
TI  - Giant anal condylomatosis after allogeneic bone marrow transplantation: a rare
      complication of human papilloma virus infection.
AB  - Condyloma acuminata or genital warts are caused by human papilloma virus (HPV).
      Ongoing proliferation of HPV in patients with congenital or acquired
      immunodeficiency states leads to the development of rapidly progressive and
      sometimes locally invasive tumor with or without dysplasia. Aggressive treatment,
      diagnostic immuno-typing, and follow-up are necessary in patients with ongoing
      immunosuppression. We report a case of giant ano-genital condylomatosis due to
      HPV types 6 and 11 in a patient with chronic myeloid leukemia after allogeneic
      bone marrow transplantation. The tumor was successfully treated with surgical
      excision and local application of 5% imiquimod cream.

PMID- 17511822
TI  - Work-up for infectious diarrhea after allogeneic hematopoietic stem cell
      transplantation: single specimen testing results in cost savings without
      compromising diagnostic yield.
AB  - BACKGROUND: Diarrhea is a common complication of allogeneic bone marrow
      transplantation. Microbiologic stool studies are frequently ordered to rule out
      infectious etiology. The utility of examining multiple stool specimens per
      diarrheal episode has not been examined. METHODS: . We performed a retrospective
      review of 169 adult and pediatric patients who underwent hematopoietic stem cell
      transplantation at Memorial Sloan-Kettering Cancer Center from January 1, 2000
      though December 31, 2001, who had at least 1 microbiologic stool study. We report
      on the incidence of enteric pathogens in our population and diagnostic yield of
      stool studies. A diarrheal episode was defined as a 14-day period from the date
      of the first stool study. Cost savings analysis was based on projected savings
      from implementation of proposed guidelines to the study population. RESULTS: A
      total of 1649 stool tests were performed (mean 10.6 tests per patient). An
      infectious cause of diarrhea was found in 45 (28.8%) patients. Diagnostic yield
      was 6.2% for Clostridum difficile toxin assay, 12.9% for viral cultures, and 1.3%
      for rotavirus enzyme immunoassay. Bacterial cultures for enteric pathogens,
      examination for parasites, and rotavirus antigen assay combined had 0.5% positive
      yield. CONCLUSIONS: Testing of multiple specimens per diarrheal episode did not
      increase diagnostic yield. The estimated cost savings by implementing single
      testing for each type of stool study per diarrheal episode was $49,764 annually
      (in 2001 US dollars). Judicious use of stool tests to evaluate diarrhea results
      in significant cost savings without compromising diagnostic yield.

PMID- 17511823
TI  - Infectious complications after kidney transplantation: a single-center
      experience.
AB  - Infectious complications after renal transplantation are associated with
      significant morbidity and mortality. The prevalence of infections in transplant
      recipients varies from country to country. This study sought to assess the
      overall incidence of post-transplant infectious complications at our research
      center in Iran, compared with other centers in the world. Between 2002 and 2004,
      179 renal transplantations were performed in our center. Of these, 142 were
      studied and followed for 1 year. Immunosuppressive regimens were cyclosporine,
      mycophenolate mofetil, and prednisolone. The overall incidence of infections was
      54.2%. The most common sites of infections were the urinary tract (41.5%) and the
      respiratory tract (6.3%). The most frequent causes of infections were Klebsiella
      (24%) and cytomegalovirus (CMV) (17.6%). Wound infection occurred in 4.9% of the
      patients. Three (2.1%) patients developed hepatitis C and 2 (1.4%) had
      mycobacterial infections. There was no case of Pneumocystis pneumonia. Overall
      mortality was 7.7%. Infection-related mortality was 3.5%. In conclusion, this
      study identifies infections as the cause of morbidity and mortality in the post
      transplant period. There was a low incidence of tuberculosis (<2% yearly) and a
      high incidence of CMV disease in our recipients.

PMID- 17511824
TI  - Conversion to mycophenolate mofetil for modulating recurrent hepatitis C in liver
      transplant recipients.
AB  - BACKGROUND: The aim of this study was to analyze the influence of cyclosporine A
      (CsA) taper in conjunction with mycophenolate mofetil (MMF) therapy on recurrent
      hepatitis C virus (HCV) in liver transplant patients. PATIENTS AND METHODS:
      Nineteen liver recipients with serologically and morphologically confirmed
      recurrent HCV were included in this study. After MMF introduction up to a maximum
      dose of 2000 mg/day, CsA dose was significantly tapered. In the control group
      immunosuppression remained unchanged. Allograft function and morphology, viral
      loads, and renal function were analyzed continuously. RESULTS: MMF treatment was
      well tolerated without risk of rejection. Allograft fibrosis progressed in 6
      patients of the MMF group (66.6%) and none (0%) of the controls at 12-month
      biopsy (P=0.005). Moreover, aminotransferases and viral loads increased slightly
      in the MMF-treated patients. Renal function improved significantly (serum
      creatinine: 239.3+/-90.2 micromol/L vs. 175.8+/-46.0 micromol/L; P=0.008) in the
      treatment group, while deteriorating (serum creatinine: 156.8+/-44.6 micromol/L
      vs. 214.8+/-120.1 micromol/L; P=0.06) in the controls. CONCLUSION: MMF
      introduction allows a safe CsA taper in HCV-positive liver transplant patients
      and results in significant improvement of renal function. However, there seems to
      be a risk of marked progression of HCV-induced allograft injury.

PMID- 17511825
TI  - Occupational risk assessment of aspergillosis after renal transplantation.
AB  - Returning to work after transplantation is a much-discussed topic today,
      especially as a measure to avoid permanent work disability. Many transplant
      patients regain their ability to work 2-6 months after transplantation. However,
      returning to work should not endanger their health. This means that occupational
      risks such as occupational exposure to Aspergillus spores must be evaluated. We
      evaluated the community-acquired aspergillosis risk and in particularly the
      occupational aspergillosis risk, using the example of a 39-year-old construction
      worker immunosuppressed after renal transplantation. On one hand the risk is
      linked to the exposure to microorganisms that the individual is likely to be
      subjected to, and on the other hand to the factors that modify his state of
      susceptibility or resistance to these infectious agents. The necessity of
      immunosuppressive therapy after transplantation elevates the aspergillosis risk,
      especially 1-6 months after transplantation. There are many professions in which
      exposure to Aspergillus spores can occur. The risk of acquiring aspergillosis at
      work exists, but is not quantifiable today. Nevertheless, the risk should be
      minimized during the period of vulnerability by preventive measures such as
      restriction of certain activities, changing work methods and reorganizing the
      work day to adapt to the risk, and wearing personal protective equipment, as well
      as attention to information about aspergillosis risk and about the likelihood of
      exposure in the patient's professional and leisure activities.

PMID- 17511826
TI  - Successful treatment of recurrent cholangitis complicating liver transplantation
      by Roux-en-Y limb lengthening.
AB  - A 40-year-old male developed sepsis due to cholangitis. Five years earlier he
      underwent liver transplantation with hepaticojejunostomy. Over the past 18
      months, he had 6 episodes of cholangitis. Radiologic studies demonstrated no
      biliary obstruction. Surgical intervention to eliminate bile reflux and stasis by
      lengthening the Roux-en-Y limb from 30 to 90 cm was curative. He has had no
      further episodes of cholangitis or hospitalization in the past 2 years. This case
      is the first description to our knowledge of a simple technique to treat
      recurrent cholangitis in patients with normal biliary anatomy, but inadequate
      biliary drainage following liver transplantation.

PMID- 17511827
TI  - Immunohistochemically proven cytomegalovirus end-organ disease in solid organ
      transplant patients: clinical features and usefulness of conventional diagnostic
      tests.
AB  - We studied the main clinical features, outcome, and laboratory parameters in a
      group of solid organ transplant (SOT) patients with immunohistochemically proven
      cytomegalovirus (CMV) disease. Confirmed CMV cases were obtained through
      databases. Demographics, clinical data, transplantation type, immunosuppressive
      regimens, donor and recipient CMV serostatus, therapy, outcome and laboratory
      results, pp65 antigenemia, and qualitative polymerase chain reaction (PCR) for
      CMV were analyzed. From 1995 to 2004, 31 cases with complete medical records were
      identified. Disease appeared between 24 and 2538 days after transplantation but
      most cases presented in the first 100 days. Gastrointestinal CMV disease was the
      most frequent form (71%), while thrombocytopenia was present in 50% of cases, and
      leukopenia was less common (35.5%). CMV pp65 antigenemia was positive in 58% of
      patients, but its sensitivity increased to 71% if performed during the first 6
      months. A qualitative CMV PCR technique gave similar results during this period
      (71.4%). Most patients were treated with intravenous ganciclovir (n=25; 80.6%).
      In 4 cases (19.4%), use of foscarnet alone or a sequential regimen with
      ganciclovir-foscarnet was deemed necessary. Surgical procedures were necessary in
      5 patients (16%). The death rate reached 13%. CMV end-organ disease can be a life
      threatening infection in SOT patients. Gastrointestinal disease was the most
      frequent end-organ disease. CMV antigen detection is best suited for the early
      period after transplantation.

PMID- 17511828
TI  - Invasive fungal infections in allogeneic and autologous stem cell transplant
      recipients: a single-center study of 166 transplanted patients.
AB  - OBJECTIVES: Invasive fungal infections (IFIs) remain a major cause of infection
      related morbidity and mortality following hematopoietic stem cell transplantation
      (HSCT). PATIENTS AND METHODS: We retrospectively analyzed the incidence of IFIs
      in 166 patients undergoing either allogeneic or autologous HSCT at our
      institution between January 2000 and December 2003. RESULTS: Incidence of
      invasive aspergillosis (IA) and invasive candidiasis among allogeneic HSCT
      recipients was 23% (16-32%, 95% confidence interval [CI]) and 3% (1-9%, 95% CI),
      respectively. Duration of neutropenia and reduced-intensity conditioning were the
      only risk factors for IA in the multivariate model. Patients with IA had
      significantly reduced overall survival (8% versus 56%, P=0.01) due to higher
      transplant-related mortality (63% versus 31%, P=0.03). Following autologous HSCT,
      incidence of IA and invasive candidiasis was 8% (4-19%, 95% CI) and 2% (0.2-11%,
      95% CI), respectively. Duration of neutropenia was the only risk factor for the
      development of IA following autologous HSCT. Overall survival of autologous HSCT
      recipients with IA was similar to that of patients without IA. Seventeen percent
      of autologous HSCT recipients were colonized with Candida species. Compared with
      non-colonized patients these patients had significantly reduced overall survival
      (72% versus 23%, P=0.004), due to increased treatment-related mortality (23%
      versus 9%, P=0.02). CONCLUSION: Diagnosis of IA following allogeneic HSCT and
      Candida colonization in the setting of autologous HSCT defines patient
      populations with poor outcome but primarily not as a result of the fungal
      pathogen. Regarding the incidence of IA, duration of neutropenia is the main risk
      factor, and dose-reduced conditioning is an additional risk factor for the
      development of IA following allogeneic HSCT, probably owing to increased
      recipient age in this patient cohort, requiring further studies in this
      transplantation setting.

PMID- 17511829
TI  - Early and late urological complications corrected surgically following renal
      transplantation.
AB  - The purpose of this study was to assess outcomes of urological complications
      after kidney transplantation operation. Nine-hundred and sixty-five patients
      received a kidney transplant between 2000 and 2006. In total, 58 (6.01%)
      developed urological complications, including urinary leakage (n = 15, 1.55%),
      stenosis (n = 29, 3%), vesicoureteral reflux (VUR) (n = 12, 1.2%), calculi (n =
      1, 0.1%) and parenchymal fistulae (n = 1, 0.1%). Urinary leakage cases were
      treated by ureteroneocystostomy (UNS) via a double-J stent and stenosis cases by
      UNS. Fenestration was performed in patients developing lymphoceles and
      unresponsive to percutaneous drainage. VUR treatment was performed by
      ureteroneocystostomy revision or UNS. Stent usage during ureteric reimplantation
      was observed to reduce urinary leakage. Surgical complication rates in renal
      transplantation recipients according to donor type (living versus cadaveric) and
      the status of stent use (with stent versus without stent) were 5.53% vs. 7.27% (P
      = 0.064) and 5.24% vs. 20% (P < 0.01) respectively. No recurrence, graft loss or
      death was seen after these interventions. Comparison of recipients with and
      without urological complication showed that there was no difference between
      groups (P > 0.05) with respect to last creatinine level. No graft or patient loss
      was associated with urological complications. Urological complications that can
      be surgically corrected should be aggressively treated by experienced surgeons
      and graft loss avoided.

PMID- 17511830
TI  - Comparison between allogenic and autologous vascular conduits in the drainage of
      anterior sector in right living donor liver transplantation.
AB  - Congestion of the anterior sector may lead to graft failure in right lobe grafts.
      Selective drainage of the prominent segment 5 and/or 8 veins is proposed to
      overcome this problem. Different vascular conduits may be used during drainage of
      the anterior sector. In this study, we evaluated the efficiency of the vascular
      conduits. Between June 1999 and December 2005, 190 patients underwent living
      donor right lobe liver transplantation and reconstruction of segment 5 and/or 8
      veins was performed in 48 patients (25.2%). Two groups were formed according to
      the types of vascular conduits. Cryopreserved cadaveric iliac artery (n = 28) and
      cryopreserved cadaveric iliac vein (n = 8) were used in group A. In group B,
      recipient saphenous vein (n = 6), recipient umbilical vein (n = 5) and recipient
      collateral omental vein (n = 1) were used for reconstruction. The graft-recipient
      weight ratio, mean duration of anhepatic phase and MELD scores between two groups
      were not significantly different. All of the conduits were found to be patent
      just after reperfusion and in the early postoperative period by Doppler
      ultrasonography. In follow-up period of 1 year, four (11%) patients died in group
      A, two patients (16%) in group B. One of these patients died because of sepsis
      started from the saphenous vein incision site. None of the patients dying in the
      two groups were lost due to venous outflow problems. This study proves the
      efficacy of drainage of segment 5 and/or 8 veins using cryopreserved cadaveric
      vascular conduits. Every effort should be employed to store cadaveric iliac
      vessels, otherwise, whole other additive surgical intervention to ensure vascular
      conduit may lead uninvited serious complication.

PMID- 17511832
TI  - Tooth avulsion and replantation.

PMID- 17511831
TI  - Preoperative evaluation of microencapsulated human parathyroid tissue aids
      selection of the optimal bioartificial graft for human parathyroid
      allotransplantation.
AB  - Allotransplantation of microencapsulated parathyroid tissue is a promising
      approach to the treatment of permanent hypoparathyroidism. Preoperative
      assessment of the quality of microencapsulated parathyroid tissue could
      facilitate selection of the optimal bioartifical graft for human parathyroid
      allotransplantation. Parathyroid tissue from patients with secondary
      hyperparathyroidism (n = 15) was processed mechanically or enzymatically
      (collagenase type II). Tissue particles and single cells/cell clusters were
      routinely microencapsulated with amitogenic Ba(2+) alginate. Parathyroid
      secretion dynamics in response to stimulation of nonencapsulated and
      microencapsulated parathyroid tissue with Ca(2+) were evaluated in a perifusion
      system. The stability of the different types of microcapsule was assessed using
      an osmotic pressure test. Mechanical cutting of parathyroid tissue led to
      peripheral necrosis of tissue particles and impaired their vitality. Collagenase
      digestion, in contrast, resulted in single cells and cell clusters without
      peripheral necrosis. The quality of microencapsulation of single cells/cell
      clusters was significantly better than that of tissue particles (deformed and
      imperfect capsules). Microencapsulation itself did not decrease cell vitality.
      Nonencapsulated and microencapsulated tissue particles and single cells/cell
      clusters from different donors maintained their own levels of response to
      stimulation with low Ca(2+). Microcapsules containing tissue particles showed
      poor stability compared with those containing single cells/cell clusters.
      Preoperative evaluation of microencapsulated parathyroid tissue can disclose
      differences in vitality and function and thus facilitate selection of the optimal
      bioartifical graft for human parathyroid allotransplantation.

PMID- 17511833
TI  - Guidelines for the management of traumatic dental injuries. II. Avulsion of
      permanent teeth.
AB  - Avulsion of permanent teeth is the most serious of all dental injuries. The
      prognosis depends on the measures taken at the place of accident or the time
      immediately after the avulsion. Replantation is the treatment of choice, but
      cannot always be carried out immediately. An appropriate emergency management and
      treatment plan is important for a good prognosis. Guidelines are useful for
      delivering the best care possible in an efficient manner. The International
      Association of Dental Traumatology (IADT) has developed a consensus statement
      after a review of the dental literature and group discussions. Experienced
      researchers and clinicians from various specialties were included in the group.
      In cases in which the data did not appear conclusive, recommendations were based
      on the consensus opinion of the IADT board members. The guidelines represent the
      current best evidence based on literature research and professional opinion. In
      this second article of three, the IADT Guidelines for management of avulsed
      permanent teeth are presented.

PMID- 17511834
TI  - Traumatic dental injuries and attention-deficit/hyperactivity disorder: is there
      a link?
AB  - Traumatic dental injuries (TDIs) constitute a major cause of morbidity among
      children worldwide. Both TDIs and attention-deficit/hyperactivity disorder (ADHD)
      are prevalent conditions with similar male-to-female predominance and similar age
      of presentation. While the commonest causes of TDIs have been identified as
      playground or sports accidents, a well-known feature of ADHD is accident
      proneness. Violence, another significant risk factor for TDIs, is more likely to
      be observed in conduct disorder, a common comorbidity of ADHD. Also, both TDIs
      and ADHD have been found to be associated with left-handedness. The presence of
      multiple dental trauma episodes (MDTE), as well as increased risk for non-dental
      injuries in children with TDIs indicates an underlying persistent condition,
      which resembles ADHD. Higher point prevalence of mental distress at age 30, found
      to be associated with increased lifetime prevalence of TDIs, may also be taken as
      an evidence of a background developmental disorder persisting into adulthood with
      various comorbidities. In conclusion, this review combines the results of several
      studies and explains the significance of ADHD as an underlying and predisposing
      factor for TDIs. Increased awareness and close collaboration between different
      disciplines involved are essential.

PMID- 17511835
TI  - Dental injuries in inline skating - level of information and prevention.
AB  - Inline skating belongs like ice hockey, rugby, and boxing to sporting activities
      with high-risk of suffering tooth accidents. Because of high velocity and loss of
      balance, especially on uneven ground, the injury potential in inline skating is
      higher. The objective of this work was to conduct a comparative study between
      Switzerland and Germany. The questions focussed on the frequency of tooth
      accidents, their prevention by mouthguard and the level of information about
      emergency measures after dental trauma and the resulting consequences for
      athletes. Using a standardized questionnaire totally 612 individuals, 324 men and
      288 women, in two countries belonging to three different divisions (fun, fitness
      and speed) were surveyed. Fifty-six (9.2%) of these 612 interviewees have already
      experienced a tooth injury while inline skating. More than half of all
      interviewed players (68.3%) were aware of the possibility of replanting avulsed
      teeth. Only 32.4% were familiar with the tooth rescue kit. Just 65.4% knew
      mouthguard and only 1.9% of those athletes (n = 12) wore a mouthguard while
      inline skating. The results show that the area of inline skating requires more
      information about preventing dental trauma through sports associations and
      dentists.

PMID- 17511836
TI  - Fabricating a better mouthguard. Part I: factors influencing mouthguard thinning.
AB  - There is some concern regarding the amount of material thinning that occurs
      during the fabrication of custom-fabricated mouthguards. It is unclear if this
      thinning is merely a consequence of the fabrication process or related to other
      factors such as jaw size. Thus, the purpose of this study was to evaluate the
      contribution that various dimensional characteristics of the dental arch and the
      height of the stone model would have on mouthguard thinning. Fifteen subjects
      participated in this investigation. Alginate impressions from each subject were
      used to produce three replicas of the maxillary dentition with only the height of
      the base varying amongst them. The total height of the three models were 20, 25,
      and 30 mm. A single mouthguard was produced using each of the stone models. The
      material thickness of the mouthguard was assessed at the labial and occlusal
      surfaces. Additionally, the dimensions of the stone models were documented.
      Pearson product moment correlation coefficients were calculated to determine the
      linear relationship between material thickness and (i) the height of the stone
      models, (ii) the arch length and (iii) the area covered by the stone model.
      Statistical tests performed using the mean thickness values collected from the
      incisors and canines revealed a high negative correlation between the height of
      the stone model and material thickness (r = -0.82). In addition, a low to
      moderate positive linear correlation was noted between arch length and occlusal
      thickness at the molars (r = 0.57) and between the area of the stone model with
      the occlusal thickness (r = 0.49). The results of the present study indicate that
      the height of the model used to fabricate custom mouthguards should be kept as
      low as possible but still allow for the production of a properly fitting
      mouthguard.

PMID- 17511837
TI  - Self-replantation of an avulsed tooth in torsoversion: a 10-year follow-up.
AB  - A 15-year-old moderately built boy reported to the dental outpatient department
      with a complaint of pus discharge from the upper front teeth. There was a clear
      history of traumatic avulsion followed by self-replantation 6 years earlier. No
      dental treatment was taken by the child. On clinical examination the left upper
      central incisor was in torsoversion (anatomical labial surface on palatal side
      and vice versa). The child had probably self-replanted in torsoversion.
      Endodontic treatment was successfully completed, and final rehabilitation was
      done by a porcelain crown. The case highlights the excellent results of immediate
      replantation even when it is done by a child. It also highlights the value of
      school level dental education.

PMID- 17511838
TI  - Multidisciplinary approach for the treatment of an oblique root fracture: a case
      report.
AB  - This clinical case study describes a multidisciplinary modified technique for the
      treatment of an oblique root fracture. A-38-year old woman with a history of
      trauma and a broken tooth was referred to our clinic. There was an oblique crown
      fracture extending the coronal third of the root just underneath the cingulum of
      the crown. The patient was willing to keep her tooth in function by any means.
      Two weeks after root canal therapy the flap was raised. The coronal two third of
      the root canal was enlarged. An impression of the enlarged root canal and tooth
      surface with surrounding bone was taken. The flap was sutured and the impression
      was sent to the laboratory for the post-casting preparation. After 7 days, the
      flap was opened again and casting was cemented. The flap was sutured. Ten days
      after the second surgery, three anterior teeth were prepared and a final
      impression was taken for the preparation of porcelain crowns. Restoration was
      finished 15 days after the second operation. The patient is still under
      maintenance therapy and the 12 month results are presented in this report.
      Extraction may not be the only alternative for the root fractures. Even for
      fractures under the alveolar margin, alternative multidisciplinary approaches can
      be used to restore and allow the tooth to survive.

PMID- 17511839
TI  - Root fracture in immature tooth: report of a case.
AB  - Root fracture injuries affect 0.5-7% of permanent teeth. Although this type of
      injury is rarely seen in teeth with immature root formation, the prognosis is
      generally good depending on the site of the fracture. A case report of horizontal
      root fracture in maxillary central incisor of an 8-year and 3-month-old girl and
      its treatment was presented.

PMID- 17511840
TI  - Tooth fragment reattachment after retrieval from the lower lip - a case report.
AB  - The most common traumatic dental injury is the uncomplicated crown fracture of
      the maxillary central incisor. Various reports have been written about
      reattachment of the fragment, and literature reviews have cited this technique as
      the best way of treating these injuries if the fragment is available and properly
      stored. The case presented here is of a child who sustained an uncomplicated
      crown fracture with the lost portion of the tooth embedded in his lower lip. This
      was successfully reattached to the tooth using an acid-etch and enamel-bonding
      resin technique.

PMID- 17511841
TI  - Dislocation of an upper third molar into the maxillary sinus after a severe
      trauma: a case report.
AB  - Dental injuries are common following facial trauma. This article presents a rare
      injury: the dislocation of a third molar into the maxillary sinus after complex
      mandibular and maxillary tuberosity fractures. The possible mechanism and
      clinical treatment are discussed.

PMID- 17511842
TI  - Reattachment of subgingivally fractured central incisor with an open apex.
AB  - A case report of a 6-year-old girl with a fractured maxillary left central
      incisor with an open apex is presented. The procedure used to repair the fracture
      included flap surgery with an intrasulcular incision and endodontic treatment.
      The patient was called for 3 months regular follow-up to check the root
      formation. At the end of 32 months just before the root was obturated by
      guttaperka, she fractured the same tooth. Flap surgery was repeated and the tooth
      was restored. The root canal was obturated with a root filling paste and
      guttaperka as the apex was closed. Examination 10 months after treatment revealed
      good periodontal health, aesthetics and normal function.

PMID- 17511843
TI  - Intentional replantation of a hopeless tooth with the combination of platelet
      rich plasma, bioactive glass graft material and non-resorbable membrane: a case
      report.
AB  - Intentional replantation can be an alternative choice for periodontally involved
      hopeless tooth at least for a period of time. This technique may help to restore
      an original tooth to function in the mouth instead of replacing it with
      prosthesis. The combination of one or more techniques currently available for
      periodontal therapy may have the potential to enhance clinical results as
      compared to any of the techniques used alone. In this case report, intentional
      replantation was combined with regenerative techniques. A very popular agent,
      platelet rich plasma was used in combination with bioactive glass graft material
      and non-resorbable PTFE membrane. The technique and one year results of treatment
      were discussed radiographically and clinically.

PMID- 17511844
TI  - Nosology of idiopathic transverse myelitis syndromes.
AB  - Several terms are now commonly used to describe various presentations of
      idiopathic myelitis, including acute transverse myelitis, acute partial
      transverse myelitis, and secondary myelitis. Ideally, a classification system
      would be able to encompass various presentations in a manner that not only
      assists in prognosis, but also in treatment decisions. Unfortunately, we are
      limited in our ability to accurately identify those patients who will progress to
      develop multiple sclerosis, Devic's syndrome, relapsing myelitis, or will remain
      monophasic. However, general principles are emerging that assist in prognosis
      based on the particular presenting features of any patient. We review the most
      recent criteria proposed for various forms of transverse myelitis and highlight
      the limitations of these classification schemes.

PMID- 17511845
TI  - Non-invasive assessment of cardioregulatory autonomic functions in children with
      epilepsy.
AB  - OBJECTIVES: We aimed to evaluate the interictal cardiovascular autonomic
      functions in pediatric patients with idiopathic epilepsy, both partial and
      generalized. MATERIALS AND METHODS: The study included 25 patients with
      idiopathic epilepsy and 50 control subjects. Patients underwent five standardized
      clinical cardiovascular reflex autonomic tests [resting heart rate (HR), HR
      response to deep breathing and to Valsalva maneuver, the 30:15 ratio of HR
      response to standing, and blood pressure response to standing], as well as a 12
      lead surface electrocardiogram. Heart rate variability (HRV) was tested via 24-h
      Holter monitoring and the time domain parameters (SDNN, PNN50, rMSDD) were
      assessed. Excretion of vanillyl mandelic acid and metanephrine was measured in 24
      h urine collection. RESULTS: Clinical reflex autonomic tests showed mild
      dysfunction in 8%, moderate dysfunction in 44% and severe dysfunction in 4% of
      patients. The HRV parameter, SDNN, was reduced in all age groups, while rMSDD and
      PNN50 were reduced only in the older age group. Metanephrine levels were
      significantly reduced in the patients group. Patients with uncontrolled epilepsy
      had a significantly higher frequency of autonomic dysfunction as assessed by
      clinical scoring. CONCLUSION: Cardiac autonomic dysfunction is not uncommon in
      pediatric patients with epilepsy. Altered cardiovascular regulation seems to be
      related to the epilepsy itself rather than to the characteristics of the
      disorder.

PMID- 17511846
TI  - Irreversible motor impairment in young addicts--ephedrone, manganism or both?
AB  - BACKGROUND: Parkinsonian syndrome related to intravenous use of a "designer"
      psychostimulant, derived from pseudoephedrine using potassium permanganate as the
      oxidant, has been observed in drug addicts in Estonia. OBJECTIVE: To describe the
      symptomatology of four young patients, history of drug administration and
      chemical analysis of a drug batch. METHODS: Mental and motor function and quality
      of life were scored and ephedrone was analyzed using electrospray mass
      spectrometry. Manganese content of the final synthetic mixture was analyzed using
      Inductively Coupled Plasma-Atomic Emission Spectrometry. RESULTS: None of the
      four cases scored below the dementia threshold in MMSE, while other ratings
      (UPDRS, H&Y, PDQ-39) corresponded to disabilities seen in relatively advanced
      Parkinson's disease. The ephedrone yield of the reaction was approximately 44%
      and the mixture was found to contain 0.6 g/l of manganese. CONCLUSIONS: The cases
      were exposed to extreme manganese load. Their symptomatology is probably
      identical to manganism. The role of ephedrone is presently unknown. Physicians
      must be aware of early signs of manganism in patients within social risk groups.

PMID- 17511847
TI  - A handheld nerve conduction measuring device in carpal tunnel syndrome.
AB  - OBJECTIVES: The diagnostic utility and reliability of an easy-to-operate novel
      handheld nerve conduction tester in carpal tunnel syndrome (CTS) were evaluated.
      MATERIALS AND METHODS: Using the test device, the sensory nerve conductions (SNC)
      in the median and ulnar nerves were compared with each other in 194 patients with
      suspected CTS and 95 healthy controls. The test device results were compared with
      the results of nerve conduction studies (NCS) with traditional instrumentation.
      RESULTS: The new device correctly classified 145 of the 149 hands (97.3%) without
      median nerve lesion and 171 of the 200 hands (85.5%) with median nerve lesions in
      traditional NCS. The specificity of the new tester compared with traditional
      instrumentation was 98%. The correlation coefficient for different technicians in
      different studies was 0.87. CONCLUSIONS: The findings obtained with the new
      tester in CTS were reliable and reproducible. This tester may increase
      availability of NCS in CTS.

PMID- 17511848
TI  - Five-year outcome after mild head injury: a prospective controlled study.
AB  - OBJECTIVES: To study the prevalence of post-concussion symptoms (PCS) 5-7 years
      after mild head injury (MHI) and to investigate whether patients suffer from more
      symptoms than the normal population. METHODS: We conducted a 5- to 7-year follow
      up of patients (n = 89) with MHI. Post-concussion symptoms were quantified with
      the Rivermead Post Concussion Symptoms Questionnaire (RPQ) and health-related
      quality of life (HRQL) was measured with the EuroQol-5D (EQ-5D). We also
      quantified subjective general health state with the EuroQol Visual Analogue Scale
      (EQ-VAS). An age- and sex-matched, but otherwise randomly chosen control group of
      89 persons was recruited from the National Population Registry for a cross
      sectional comparison. Twenty-eight patients (30%) and 27 (30%) controls
      responded. RESULTS: Patients reported significantly (P = 0.017) more PCS (median
      RPQ score 10, 95% CI 2-20) than controls (median 2, 95% CI 0-4). They also
      reported significantly (P = 0.008) lower HRQL (median EQ-5D score 0.866, 95% CI
      0.796-1.000) than controls (1.000, 95% CI 1.000-1.000), but there was no
      difference between the groups in their subjective ratings of general health
      state. CONCLUSIONS: Patients reported significantly more PCS and lower HRQL 5 to
      7 years after MHI than age- and sex-matched controls from the normal population.

PMID- 17511849
TI  - The integrity of the blood-brain barrier in Alzheimer's disease.
AB  - OBJECTIVE: To evaluate the integrity of the blood-brain barrier (BBB) in incident
      Alzheimer's disease (AD). MATERIALS AND METHODS: The mean age of the 157 patients
      (45% men) was 69.7(9.4) years (range 51-88 years). The patients had undergone a
      thorough investigation including magnetic resonance imaging or computed
      tomography of the brain. The cerebrospinal(CSF)/plasma albumin ratio (albumin
      ratio) was used as a measure of BBB function. RESULTS: There were gender
      differences with respect to albumin ratio and plasma creatinine with higher
      values in men (P < 0.001). 42% of the men and 13% of the women (P < 0.001) had a
      mild to moderate BBB dysfunction when applying the reference limit of the
      laboratory (<9.2). Both male gender (P = 0.002) and plasma creatinine (P = 0.009)
      were independently associated with the albumin ratio when controlling for
      putative confounders. CONCLUSIONS: The BBB is dysfunctional in a portion of
      patients with AD, both women and, primarily, men. The dysfunction might influence
      the clearance of both harmful and beneficial substances across the barrier. Renal
      function might have an impact on the BBB.

PMID- 17511850
TI  - Lack of difference in the intimal medial thickness between the left and right
      carotid arteries in the young.
AB  - BACKGROUND: Carotid intimal medial thickening (c-IMT) is an established surrogate
      marker for atherosclerosis. There have been sporadic reports about an increase of
      c-IMT on the left carotid artery among populations with a mean age of +/-50
      years. OBJECTIVE: The purpose of this study was to evaluate whether there is a
      difference in c-IMT between the two carotid arteries in a group of young healthy
      adults. METHODS: Ninety-eight healthy adults with a mean age of 28 years
      underwent blood tests to evaluate various cardiovascular risk factors as well as
      automated ultrasonic measurements of their c-IMT on both carotid arteries.
      RESULTS: No significant difference was noted between c-IMT on both sides. In
      fact, the c-IMT on left carotid artery in men (n = 52) was 0.625 +/- 0.078 mm
      while on the right carotid it was 0.626 +/- 0.075 mm (P = 0.884). The values for
      women (n = 46) were 0.615 +/- 0.059 mm and for men 0.622 +/- 0.0618 mm (P =
      0.582), respectively. CONCLUSION: As opposed to a noted increase of c-IMT on the
      left carotid artery in older individuals, we did not find this difference in a
      group of young and relatively healthy adults. It is possible that if mechanical
      stress forces contribute to an enhanced left c-IMT, it takes a relatively long
      time to become evident.

PMID- 17511851
TI  - Chemokine receptor CCR5 in interferon-treated multiple sclerosis.
AB  - OBJECTIVE: To study the relationship between CC chemokine receptor CCR5
      expression and disease activity in multiple sclerosis (MS) patients treated with
      beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter
      polymorphism associated with cell surface expression of CCR5 were analyzed in 109
      patients with relapsing-remitting MS treated with IFN-beta who were followed
      clinically for 1 year. Cellular CCR5 expression was measured by flow cytometry.
      RESULTS: Patients with MS had a higher percentage of CCR5-positive monocytes than
      healthy controls. Increased monocyte expression of CCR5 correlated weakly with an
      increased short-term relapse risk but there was no relationship between CCR5
      Delta32 allele and CCR5 promoter polymorphism genotypes and relapse risk.
      CONCLUSIONS: The results do not support a major role of CCR5 in the pathogenesis
      of relapses in MS patients treated with IFN-beta, but it is possible that
      monocyte CCR5 expression may be used as a marker of disease activity.

PMID- 17511852
TI  - Vascular risk factors and white matter hyperintensities in patients with amnestic
      mild cognitive impairment.
AB  - BACKGROUND: Subjects affected by aMCI are considered at high risk for AD.
      Nevertheless, the role of both vascular risk factors and WMH is matter of debate.
      PATIENTS AND METHODS: We enrolled consecutively 21 aMCI subjects according to
      Petersen Criteria; the study included routine screening for dementia,
      neuropsychological evaluation and brain MRI. Six vascular risk factors were
      assessed and WMH was quantified by means of a semiautomatic lesion-detection
      program. RESULTS: Conversion to AD, according to NINCDS-ADRDA criteria, was
      47.6%. Converters tended to be more affected by the most of vascular risk factors
      while no difference was noted in WMH. The best predictors of conversion to AD
      were scores obtained at several neuropsychological examination. CONCLUSION: Our
      results show that criteria for aMCI identify subjects with a high risk to develop
      AD. WMH doesn't seem to have a role in progression from aMCI to AD, while some
      vascular risk factors seem to promote it.

PMID- 17511853
TI  - A case of hippocampal laminar necrosis following complex partial status
      epilepticus.
AB  - Cortical laminar necrosis (CLN) is a metabolic injury pattern usually observed
      after cerebral hypoxia, hypoglycemia, or ischemia. We report serial magnetic
      resonance imaging findings in a patient with complex partial status epilepticus
      (SE) developing a band-like, T1-hyperintense lesion consistent with CLN along the
      surface of the left hippocampus without concurrent other causes of CLN. This
      observation suggests a direct pathogenetic link between SE and CLN involving
      combined damage to neurons and glia.

PMID- 17511854
TI  - Effect of early interferon beta-1a therapy on conversion to multiple sclerosis in
      Iranian patients with a first demyelinating event.
AB  - BACKGROUND: A new treatment approach to multiple sclerosis (MS) is the initiation
      of interferon therapy in the early phase of the disease when a patient presents
      with clinically isolated syndrome. AIMS OF THE STUDY: The goal of this study was
      to assess the effect of early treatment on the risk of conversion to clinically
      definite MS in Iranian patients. METHODS: Eligible patients had presented with a
      first episode of neurological dysfunction suggesting MS within the previous 3
      months and had abnormal brain magnetic resonance imaging (MRI). Patients were
      randomly assigned to receive intramuscular interferon beta 1a 30 mug or placebo
      once a week for 3 years. RESULTS: Of the 217 patients randomized, 202 patients
      completed the study; 104 received Avonex and 98 received placebo. Fewer patients
      converted to clinically definite multiple sclerosis in the treated group than in
      the placebo group during the study (36.6% vs 58.2%, P < 0.003). The number of
      active T2-weighted MRI lesions was significantly lower in the treated group.
      CONCLUSIONS: The results of our study, which are consistent with those from
      western studies, show that treatment at an early stage of MS delays conversion to
      definite MS and has positive effects on MRI outcomes.

PMID- 17511855
TI  - Vasculitic neuropathy--electrodiagnostic findings and association with
      malignancies.
AB  - BACKGROUND: Vasculitic neuropathies occur in the context of systemic disorders or
      in isolation. Histopathologic evaluation remains the gold standard for diagnosis,
      but certain electrodiagnostic findings may heighten suspicion of vasculitic
      neuropathy and improve the yield of nerve and muscle biopsy. AIM OF THE STUDY:
      Description of electrodiagnostic patterns associated with vasculitic
      neuropathies, and a report of a possible association with malignancies. METHODS:
      Retrospective review of medical records of patients with histopathologically
      proven vasculitic and non-vasculitic axonal neuropathies evaluated at the
      University of Pittsburgh Medical Center from November 1995 to November 2003.
      RESULTS: The most distinctive electrodiagnostic patterns associated with
      vasculitic neuropathy were mononeuritis multiplex (27.5% vs 4% in controls; P =
      0.003) and axonal sensorimotor polyneuropathy with side-to-side amplitude
      asymmetry (50% vs 32%, P > 0.05). Additionally, six patients (15% vs 2%; P =
      0.034) developed various malignancies within 2 years of onset of vasculitic
      neuropathy. CONCLUSIONS: While generalized polyneuropathy was the most common
      presentation of nerve vasculitis, our study affirms side-to-side amplitude
      asymmetry and mononeuritis multiplex as the most distinctive electrodiagnostic
      features. The frequent occurrence of malignancies suggests a possible association
      with the vasculitic neuropathy and warrants additional investigation.

PMID- 17511856
TI  - A stochastic simulation model to determine the sample size of repeated national
      surveys to document freedom from bovine herpesvirus 1 (BoHV-1) infection.
AB  - BACKGROUND: International trade regulations require that countries document their
      livestock's sanitary status in general and freedom from specific infective agents
      in detail provided that import restrictions should be applied. The latter is
      generally achieved by large national serological surveys and risk assessments.
      The paper describes the basic structure and application of a generic stochastic
      model for risk-based sample size calculation of consecutive national surveys to
      document freedom from contagious disease agents in livestock. METHODS: In the
      model, disease spread during the time period between two consecutive surveys was
      considered, either from undetected infections within the domestic population or
      from imported infected animals. The @Risk model consists of the domestic spread
      in-between two national surveys; the infection of domestic herds from animals
      imported from countries with a sanitary status comparable to Switzerland or lower
      sanitary status and the summary sheet which summed up the numbers of resulting
      infected herds of all infection pathways to derive the pre-survey prevalence in
      the domestic population. Thereof the pre-survey probability of freedom from
      infection and required survey sample sizes were calculated. A scenario for
      detection of infected herds by general surveillance was included optionally.
      RESULTS: The model highlights the importance of residual domestic infection
      spread and characteristics of different import pathways. The sensitivity analysis
      revealed that number of infected, but undetected domestic herds and the
      multiplicative between-survey-spread factor were most correlated with the pre
      survey probability of freedom from infection and the resulting sample size,
      respectively. Compared to the deterministic pre-cursor model, the stochastic
      model was therefore more sensitive to the previous survey's results. Undetected
      spread of infection in the domestic population between two surveys gained more
      importance than infection through animals of either import pathway. CONCLUSION:
      The model estimated the pre-survey probability of freedom from infection
      accurately as was shown in the case of infectious bovine rhinotracheitis (IBR).
      With this model, a generic tool becomes available which can be adapted to
      changing conditions related to either importing or exporting countries.

PMID- 17511857
TI  - A new look at the ventral nerve centre of Sagitta: implications for the
      phylogenetic position of Chaetognatha (arrow worms) and the evolution of the
      bilaterian nervous system.
AB  - BACKGROUND: The Chaetognatha (arrow worms) are a group of marine carnivores whose
      phylogenetic relationships are still vigorously debated. Molecular studies have
      as yet failed to come up with a stable hypothesis on their phylogenetic position.
      In a wide range of metazoans, the nervous system has proven to provide a wealth
      of characters for analysing phylogenetic relationships (neurophylogeny).
      Therefore, in the present study we explored the structure of the ventral nerve
      centre ("ventral ganglion") in Sagitta setosa with a set of histochemical and
      immunohistochemical markers. RESULTS: In specimens that were immunolabeled for
      acetylated-alpha tubulin the ventral nerve centre appeared to be a condensed
      continuation of the peripheral intraepidermal nerve plexus. Yet, synapsin
      immunolocalization showed that the ventral nerve centre is organized into a
      highly ordered array of ca. 80 serially arranged microcompartments.
      Immunohistochemistry against RFamide revealed a set of serially arranged
      individually identifiable neurons in the ventral nerve centre that we charted in
      detail. CONCLUSION: The new information on the structure of the chaetognath
      nervous system is compared to previous descriptions of the ventral nerve centre
      which are critically evaluated. Our findings are discussed with regard to the
      debate on nervous system organisation in the last common bilaterian ancestor and
      with regard to the phylogenetic affinities of this Chaetognatha. We suggest to
      place the Chaetognatha within the Protostomia and argue against hypotheses which
      propose a deuterostome affinity of Chaetognatha or a sister-group relationship to
      all other Bilateria.

PMID- 17511858
TI  - Inhibition of indoleamine 2,3-dioxygenase-mediated tryptophan catabolism
      accelerates collagen-induced arthritis in mice.
AB  - Indoleamine 2,3-dioxygenase (IDO) is one of the initial and rate-limiting enzymes
      involved in the catabolism of the essential amino acid tryptophan. In cultured
      cells, the induction of IDO leads to depletion of tryptophan and tryptophan
      starvation. Recent studies suggest that modulation of tryptophan concentration
      via IDO plays a fundamental role in innate immune responses. Induction of IDO by
      interferon-gamma in macrophages and dendritic cells results in tryptophan
      depletion and suppresses the immune-mediated activation of fibroblasts and T, B,
      and natural killer cells. To assess the role of IDO in collagen-induced arthritis
      (CIA), a model of rheumatoid arthritis characterized by a primarily Th1-like
      immune response, activity of IDO was inhibited by 1-methyl-tryptophan (1-MT) in
      vivo. The results showed significantly increased incidence and severity of CIA in
      mice treated with 1-MT. Activity of IDO, as determined by measuring the levels of
      kynurenine/tryptophan ratio in the sera, was increased in the acute phase of
      arthritis and was higher in collagen-immunized mice that did not develop
      arthritis. Treatment with 1-MT resulted in an enhanced cellular and humoral
      immune response and a more dominant polarization to Th1 in mice with arthritis
      compared with vehicle-treated arthritic mice. The results demonstrated that
      development of CIA was associated with increased IDO activity and enhanced
      tryptophan catabolism in mice. Blocking IDO with 1-MT aggravated the severity of
      arthritis and enhanced the immune responses. These findings suggest that IDO may
      play an important and novel role in the negative feedback of CIA and possibly in
      the pathogenesis of rheumatoid arthritis.

PMID- 17511861
TI  - Rivoflavin may interfere with on-line monitoring of secreted green fluorescence
      protein fusion proteins in Pichia pastoris.
AB  - BACKGROUND: Together with the development of optical sensors, fluorometry is
      becoming an increasingly attractive tool for the monitoring of cultivation
      processes. In this context, the green fluorescence protein (GFP) has been
      proposed as a molecular reporter when fused to target proteins to study their
      subcellular localization or secretion behaviour. The present work evaluates the
      use of the GFP fusion partner for monitoring extracellular production of a
      Rhizopus oryzae lipase (ROL) in Pichia pastoris by means of 2D-fluorimetric
      techniques RESULTS: In this study, the GFP-ROL fusion protein was successfully
      produced as a secreted fusion form in P. pastoris batch cultivations.
      Furthermore, both the fusion enzyme and the fluorescent protein (GFP S65T mutant)
      retained their biological activity. However, when multiwavelength
      spectrofluorometry was used for extracellular fusion protein monitoring,
      riboflavin appeared as a major interfering component with GFP signal. Only when
      riboflavin was removed by ultrafiltration from cultivation supernatants, GFP
      fluorescence signal linearly correlated to lipase activity CONCLUSION: P.
      pastoris appears to secrete/excrete significant amounts of riboflavin to the
      culture medium. When attempting to monitor extracellular protein production in P.
      pastoris using GFP fusions combined with multiwavelength spectrofluorimetric
      techniques, riboflavin may interfere with GFP fluorescence signal, thus limiting
      the application of some GFP variants for on-line extracellular recombinant
      protein quantification and monitoring purposes.

PMID- 17511860
TI  - Preferential inhibition of xanthine oxidase by 2-amino-6-hydroxy-8-mercaptopurine
      and 2-amino-6-purine thiol.
AB  - BACKGROUND: The anticancer drug, 6-mercaptopurine (6MP) is subjected to metabolic
      clearance through xanthine oxidase (XOD) mediated hydroxylation, producing 6
      thiouric acid (6TUA), which is excreted in urine. This reduces the effective
      amount of drug available for therapeutic efficacy. Co-administration of
      allopurinol, a suicide inhibitor of XOD, which blocks the hydroxylation of 6MP
      inadvertently enhances the 6MP blood level, counters this reduction. However,
      allopurinol also blocks the hydroxylation of hypoxanthine, xanthine (released
      from dead cancer cells) leading to their accumulation in the body causing
      biochemical complications such as xanthine nephropathy. This necessitates the use
      of a preferential XOD inhibitor that selectively inhibits 6MP transformation, but
      leaves xanthine metabolism unaffected. RESULTS: Here, we have characterized two
      such unique inhibitors namely, 2-amino-6-hydroxy-8-mercaptopurine (AHMP) and 2
      amino-6-purinethiol (APT) on the basis of IC50 values, residual activity in bi
      substrate simulative reaction and the kinetic parameters like Km, Ki, kcat. The
      IC50 values of AHMP for xanthine and 6MP as substrate are 17.71 +/- 0.29 microM
      and 0.54 +/- 0.01 microM, respectively and the IC50 values of APT for xanthine
      and 6MP as substrates are 16.38 +/- 0.21 microM and 2.57 +/- 0.08 microM,
      respectively. The Ki values of XOD using AHMP as inhibitor with xanthine and 6MP
      as substrate are 5.78 +/- 0.48 microM and 0.96 +/- 0.01 microM, respectively. The
      Ki values of XOD using APT as inhibitor with xanthine and 6MP as substrate are
      6.61 +/- 0.28 microM and 1.30 +/- 0.09 microM. The corresponding Km values of XOD
      using xanthine and 6MP as substrate are 2.65 +/- 0.02 microM and 6.01 +/- 0.03
      microM, respectively. The results suggest that the efficiency of substrate
      binding to XOD and its subsequent catalytic hydroxylation is much superior for
      xanthine in comparison to 6MP. In addition, the efficiency of the inhibitor
      binding to XOD is much more superior when 6MP is the substrate instead of
      xanthine. We further undertook the toxicological evaluation of these inhibitors
      in a single dose acute toxicity study in mice and our preliminary experimental
      results suggested that the inhibitors were equally non-toxic in the tested doses.
      CONCLUSION: We conclude that administration of either APT or AHMP along with the
      major anti-leukemic drug 6MP might serve as a good combination cancer
      chemotherapy regimen.

PMID- 17511859
TI  - Detection of excretory Entamoeba histolytica DNA in the urine, and detection of
      E. histolytica DNA and lectin antigen in the liver abscess pus for the diagnosis
      of amoebic liver abscess.
AB  - BACKGROUND: Amoebic liver abscess (ALA) and pyogenic liver abscesses (PLA) appear
      identical by ultrasound and other imaging techniques. Collection of blood or
      liver abscess pus for diagnosis of liver abscesses is an invasive procedure, and
      the procedure requires technical expertise and disposable syringes. Collection of
      urine is a noninvasive procedure. Therefore, there has been much interest shown
      towards the use of urine as an alternative clinical specimen for the diagnosis of
      some parasitic infections. Here, we report for the first time the detection of E.
      histolytica DNA excreted in the urine for diagnosis of the cases of ALA. RESULTS:
      E. histolytica DNA was detected in liver abscess pus specimen of 80.4% of ALA
      patients by a nested multiplex polymerase chain reaction (PCR) targeting 16S-like
      r RNA gene. The nested PCR detected E. histolytica DNA in all 37 (100%) liver
      abscess pus specimens collected prior to metronidazole treatment, but were
      detected in only 53 of 75 (70.6%) pus specimens collected after therapy with
      metronidazole. Similarly, the PCR detected E. histolytica DNA in 21 of 53 (39.6%)
      urine specimens of ALA patients. The test detected E. histolytica DNA in only 4
      of 23 (17.4%) urine specimens collected prior to metronidazole treatment, but
      were detected in 17 of 30 (56.7%) urine specimens collected after treatment with
      metronidazole. The enzyme-linked immunosorbent assay (ELISA) for the detection of
      lectin E. histolytica antigen in the liver abscess pus showed a sensitivity of
      50% and the indirect haemagglutination (IHA) test for detection of amoebic
      antibodies in the serum showed a sensitivity of 76.8% for the diagnosis of the
      ALA. CONCLUSION: The present study for the first time shows that the kidney
      barrier in ALA patients is permeable to E. histolytica DNA molecule resulting in
      excretion of E. histolytica DNA in urine which can be detected by PCR. The study
      also shows that the PCR for detection of E. histolytica DNA in urine of patients
      with ALA can also be used as a prognostic marker to assess the course of the
      diseases following therapy by metronidazole. The detection of E. histolytica DNA
      in urine specimen of ALA patients provides a new approach for the diagnosis of
      ALA.

PMID- 17511862
TI  - Questionnaire discrimination: (re)-introducing coefficient delta.
AB  - BACKGROUND: Questionnaires are used routinely in clinical research to measure
      health status and quality of life. Questionnaire measurements are traditionally
      formally assessed by indices of reliability (the degree of measurement error) and
      validity (the extent to which the questionnaire measures what it is supposed to
      measure). Neither of these indices assesses the degree to which the questionnaire
      is able to discriminate between individuals, an important aspect of measurement.
      This paper introduces and extends an existing index of a questionnaire's ability
      to distinguish between individuals, that is, the questionnaire's discrimination.
      METHODS: Ferguson (1949) 1 derived an index of test discrimination, coefficient
      delta, for psychometric tests with dichotomous (correct/incorrect) items. In this
      paper a general form of the formula, deltaG, is derived for the more general
      class of questionnaires allowing for several response choices. The calculation
      and characteristics of deltaG are then demonstrated using questionnaire data (GHQ
      12) from 2003-2004 British Household Panel Survey (N = 14761). Coefficients for
      reliability (alpha) and discrimination (deltaG) are computed for two commonly
      used GHQ-12 coding methods: dichotomous coding and four-point Likert-type coding.
      RESULTS: Both scoring methods were reliable (alpha > 0.88). However, deltaG was
      substantially lower (0.73) for the dichotomous coding of the GHQ-12 than for the
      Likert-type method (deltaG = 0.96), indicating that the dichotomous coding,
      although reliable, failed to discriminate between individuals. CONCLUSION:
      Coefficient deltaG was shown to have decisive utility in distinguishing between
      the cross-sectional discrimination of two equally reliable scoring methods.
      Ferguson's delta has been neglected in discussions of questionnaire design and
      performance, perhaps because it has not been implemented in software and was
      restricted to questionnaires with dichotomous items, which are rare in health
      care research. It is suggested that the more general formula introduced here is
      reported as deltaG, to avoid the implication that items are dichotomously coded.

PMID- 17511863
TI  - Hand is a direct target of the forkhead transcription factor Biniou during
      Drosophila visceral mesoderm differentiation.
AB  - BACKGROUND: The visceral trunk mesoderm in Drosophila melanogaster develops under
      inductive signals from the ectoderm. This leads to the activation of the key
      regulators Tinman, Bagpipe and Biniou that are crucial for specification of the
      circular visceral muscles. How further differentiation is regulated is widely
      unknown, therefore it seems to be essential to identify downstream target genes
      of the early key regulators. In our report we focus on the analysis of the
      transcriptional control of the highly conserved transcription factor Hand in
      circular visceral muscle cells, providing evidence that the hand gene is a direct
      target of Biniou. RESULTS: Herein we describe the identification of a regulatory
      region in the hand gene essential and sufficient for the expression in the
      visceral mesoderm during embryogenesis. We found that hand expression in the
      circular visceral mesoderm is abolished in embryos mutant for the FoxF domain
      containing transcription factor Biniou. Furthermore we demonstrate that Biniou
      regulates hand expression by direct binding to a 300 bp sequence element, located
      within the 3rd intron of the hand gene. This regulatory element is highly
      conserved in different Drosophila species. In addition, we provide evidence that
      Hand is dispensable for the initial differentiation of the embryonic visceral
      mesoderm. CONCLUSION: In the present report we show that cross species sequence
      comparison of non-coding sequences between orthologous genes is a powerful tool
      to identify conserved regulatory elements. Combining functional dissection
      experiments in vivo and protein/DNA binding studies we identified hand as a
      direct target of Biniou in the circular visceral muscles.

PMID- 17511864
TI  - Costs of a successful public-private partnership for TB control in an urban
      setting in Nepal.
AB  - BACKGROUND: In South Asia a large number of patients seek treatment for TB from
      private practitioners (PPs), and there is increasing international interest in
      involving PPs in TB control. To evaluate the feasibility, effectiveness and costs
      of public-private partnerships (PPPs) for TB control, a PPP was developed in
      Lalitpur municipality, Nepal, where it is estimated that 50% of patients with TB
      are managed in the private sector. From the clinical perspective the PPP was
      shown to be effective. The aim of this paper is to assess and report on the costs
      involved in the PPP scheme. METHODS: The approach to costing took a comprehensive
      view, with inclusion of costs not only incurred by health facilities but also
      social costs borne by patients and their escorts. Semi-structured questionnaires
      and guided interviews were used to collect start-up and recurrent costs for the
      scheme. RESULTS: Overall costs for treating a TB patient under the PPP scheme
      averaged US$89.60. Start-up costs per patient represented 12% of the total
      budget. Half of recurrent costs were incurred by patients and their escorts, with
      institutional costs representing most of the rest. Female patients tended to
      spend more and patients referred from the private sector had the highest reported
      costs. CONCLUSION: Treating TB patients in the PPP scheme had a low additional
      cost, while doubling the case notification rate and maintaining a high success
      rate. Costs incurred by patients and their escorts were the largest contributors
      to the overall total. This suggests a focus for follow-up studies and for cost
      minimisation strategies.

PMID- 17511865
TI  - Minocycline-induced hypersensitivity syndrome presenting with meningitis and
      brain edema: a case report.
AB  - BACKGROUND: Hypersentivity Syndrome (HS) may be a life-threatening condition. It
      frequently presents with fever, rash, eosinophilia and systemic manifestations.
      Mortality can be as high as 10% and is primarily due to hepatic failure. We
      describe what we believe to be the first case of minocycline-induced HS with
      accompanying lymphocytic meningitis and cerebral edema reported in the
      literature. CASE PRESENTATION: A 31-year-old HIV-positive female of African
      origin presented with acute fever, lymphocytic meningitis, brain edema, rash,
      eosinophilia, and cytolytic hepatitis. She had been started on minocycline for
      inflammatory acne 21 days prior to the onset of symptoms. HS was diagnosed
      clinically and after exclusion of infectious causes. Minocycline was withdrawn
      and steroids were administered from the second day after presentation because of
      the severity of the symptoms. All signs resolved by the seventh day and steroids
      were tailed off over a period of 8 months. CONCLUSION: Clinicians should maintain
      a high index of suspicion for serious adverse reactions to minocycline including
      lymphocytic meningitis and cerebral edema among HIV-positive patients, especially
      if they are of African origin. Safer alternatives should be considered for
      treatment of acne vulgaris. Early recognition of the symptoms and prompt
      withdrawal of the drug are important to improve the outcome.

PMID- 17511866
TI  - Improvement of activity and stability of chloroperoxidase by chemical
      modification.
AB  - BACKGROUND: Enzymes show relative instability in solvents or at elevated
      temperature and lower activity in organic solvent than in water. These limit the
      industrial applications of enzymes. RESULTS: In order to improve the activity and
      stability of chloroperoxidase, chloroperoxidase was modified by citraconic
      anhydride, maleic anhydride or phthalic anhydride. The catalytic activities,
      thermostabilities and organic solvent tolerances of native and modified enzymes
      were compared. In aqueous buffer, modified chloroperoxidases showed similar Km
      values and greater catalytic efficiencies kcat/Km for both sulfoxidation and
      oxidation of phenol compared to native chloroperoxidase. Of these modified
      chloroperoxidases, citraconic anhydride-modified chloroperoxidase showed the
      greatest catalytic efficiency in aqueous buffer. These modifications of
      chloroperoxidase increased their catalytic efficiencies for sulfoxidation by
      12%~26% and catalytic efficiencies for phenol oxidation by 7%~53% in aqueous
      buffer. However, in organic solvent (DMF), modified chloroperoxidases had lower
      Km values and higher catalytic efficiencies kcat/Km than native chloroperoxidase.
      These modifications also improved their thermostabilities by 1~2-fold and solvent
      tolerances of DMF. CD studies show that these modifications did not change the
      secondary structure of chloroperoxidase. Fluorescence spectra proved that these
      modifications changed the environment of tryptophan. CONCLUSION: Chemical
      modification of epsilon-amino groups of lysine residues of chloroperoxidase using
      citraconic anhydride, maleic anhydride or phthalic anhydride is a simple and
      powerful method to enhance catalytic properties of enzyme. The improvements of
      the activity and stability of chloroperoxidase are related to side chain
      reorientations of aromatics upon both modifications.

PMID- 17511867
TI  - Characterizing structural features of cuticle-degrading proteases from fungi by
      molecular modeling.
AB  - BACKGROUND: Serine proteases secreted by nematode and insect pathogenic fungi are
      bio-control agents which have commercial potential for developing into effective
      bio-pesticides. A thorough understanding of the structural and functional
      features of these proteases would significantly assist with targeting the design
      of efficient bio-control agents. RESULTS: Structural models of serine proteases
      PR1 from entomophagous fungus, Ver112 and VCP1 from nematophagous fungi, have
      been modeled using the homology modeling technique based on the crystal
      coordinate of the proteinase K. In combination with multiple sequence alignment,
      these models suggest one similar calcium-binding site and two common disulfide
      bridges in the three cuticle-degrading enzymes. In addition, the predicted models
      of the three cuticle-degrading enzymes present an essentially identical backbone
      topology and similar geometric properties with the exception of a limited number
      of sites exhibiting relatively large local conformational differences only in
      some surface loops and the N-, C termini. However, they differ from each other in
      the electrostatic surface potential, in hydrophobicity and size of the S4
      substrate-binding pocket, and in the number and distribution of hydrogen bonds
      and salt bridges within regions that are part of or in close proximity to the S2
      loop. CONCLUSION: These differences likely lead to variations in substrate
      specificity and catalytic efficiency among the three enzymes. Amino acid
      polymorphisms in cuticle-degrading enzymes were discussed with respect to
      functional effects and host preference. It is hoped that these structural models
      would provide a further basis for exploitation of these serine proteases from
      pathogenic fungi as effective bio-control agents.

PMID- 17511868
TI  - The role of survivin in angiogenesis during zebrafish embryonic development.
AB  - BACKGROUND: Survivin is the smallest member of the inhibitor of apoptosis (IAP)
      gene family. Recently, the zebrafish survivin-1 gene has been cloned, showing
      remarkable sequence identity and similarity over the BIR domain compared with
      human and mouse survivin gene. Here we investigated the role of survivin in
      angiogenesis during zebrafish development. Morpholinos (MOs) targeting the 5'
      untranslated region (UTR) (SurUTR) and sequences flanking the initiation codon
      (SurATG) of zebrafish survivin-1 gene were injected into embryos at 1-4 cell
      stage. Vasculature was examined by microangiography and GFP expression in
      Tg(fli1:EGFP)y1 embryos. RESULTS: In embryos co-injected with SurUTR and SurATG
      MOs, vasculogenesis was intact but angiogenesis was markedly perturbed,
      especially in the inter-segmental vessels (ISV) and dorsal longitudinal
      anastomotic vessels (DLAV) of the trunk, the inner optic circle and optic veins
      of developing eyes and the sub-intestinal vessels. Apoptosis was increased, as
      shown by TUNEL staining and increase in caspase-3 activity. Efficacy of SurUTR
      and SurATG-MOs was demonstrated by translation inhibition of co-injected 5'UTR
      survivin:GFP plasmids. The phenotypes could be recapitulated by splice-site MO
      targeting the exon2-intron junction of survivin gene and rescued by survivin
      mRNA. Injection of human vascular endothelial growth factor (VEGF) protein
      induced ectopic angiogenesis and increased survivin expression, whereas treatment
      with a VEGF receptor inhibitor markedly reduced angiogenesis and suppressed
      survivin expression. CONCLUSION: Survivin is involved in angiogenesis during
      zebrafish development and may be under VEGF regulation.

PMID- 17511869
TI  - TBMap: a taxonomic perspective on the phylogenetic database TreeBASE.
AB  - BACKGROUND: TreeBASE is currently the only available large-scale database of
      published organismal phylogenies. Its utility is hampered by a lack of taxonomic
      consistency, both within the database, and with names of organisms in external
      genomic, specimen, and taxonomic databases. The extent to which the phylogenetic
      knowledge in TreeBASE becomes integrated with these other sources is limited by
      this lack of consistency. DESCRIPTION: Taxonomic names in TreeBASE were mapped
      onto names in the external taxonomic databases IPNI, ITIS, NCBI, and uBio, and
      graph G of these mappings was constructed. Additional edges representing
      taxonomic synonymies were added to G, then all components of G were extracted.
      These components correspond to "name clusters", and group together names in
      TreeBASE that are inferred to refer to the same taxon. The mapping to NCBI
      enables hierarchical queries to be performed, which can improve TreeBASE
      information retrieval by an order of magnitude. CONCLUSION: TBMap database
      provides a mapping of the bulk of the names in TreeBASE to names in external
      taxonomic databases, and a clustering of those mappings into sets of names that
      can be regarded as equivalent. This mapping enables queries and visualisations
      that cannot otherwise be constructed. A simple query interface to the mapping and
      names clusters is available at http://linnaeus.zoology.gla.ac.uk/~rpage/tbmap.

PMID- 17511871
TI  - The median non-prostate cancer survival is more than 10 years for men up to age
      80 years who are selected and receive curative radiation treatment for prostate
      cancer.
AB  - Treatment guidelines recommend that curative radiation treatment of prostate
      cancer be offered only to men whose life expectancy is greater than 10 years. The
      average life expectancy of North American males is less than 10 years after age
      75, yet many men older than 75 years receive curative radiation treatment for
      prostate cancer. This study used the provincial cancer registry in British
      Columbia, Canada, to determine median non-prostate cancer survival for men who
      were aged 75 to 82 years at start of radiation treatment. Median survival was
      found to be greater than 10 years in men aged up to 80 years at the start of
      their radiation treatment. This finding suggests that radiation oncologists are
      able to appropriately select elderly men with greater than average life
      expectancy to receive curative radiation treatment.

PMID- 17511870
TI  - Three novel mutations in KIF21A highlight the importance of the third coiled-coil
      stalk domain in the etiology of CFEOM1.
AB  - BACKGROUND: Congenital fibrosis of the extraocular muscles types 1 and 3
      (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result
      from maldevelopment of ocular nuclei and nerves. We previously reported that most
      individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous
      mutations in KIF21A. KIF21A encodes a kinesin motor involved in anterograde
      axonal transport, and the familial and de novo mutations reported to date
      predictably alter one of only a few KIF21A amino acids--three within the third
      coiled-coil region of the stalk and one in the distal motor domain, suggesting
      they result in altered KIF21A function. To further define the spectrum of KIF21A
      mutations in CFEOM we have now identified all CFEOM probands newly enrolled in
      our study and determined if they harbor mutations in KIF21A. RESULTS: Sixteen
      CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported de novo
      KIF21A mutations were identified in three CFEOM1 probands, all located in the
      same coiled-coil region of the stalk that contains all but one of the previously
      reported mutations. Eight additional CFEOM1 probands harbored three of the
      mutations previously reported in KIF21A; seven had one of the two most common
      mutations, while one harbored the mutation in the distal motor domain. No
      mutation was detected in 5 CFEOM1 or any CFEOM3 probands. CONCLUSION: Analysis of
      sixteen CFEOM1 probands revealed three novel KIF21A mutations and confirmed three
      reported mutations, bringing the total number of reported KIF21A mutations in
      CFEOM1 to 11 mutations among 70 mutation positive probands. All three new
      mutations alter amino acids in heptad repeats within the third coiled-coil region
      of the KIF21A stalk, further highlighting the importance of alterations in this
      domain in the etiology of CFEOM1.

PMID- 17511872
TI  - Non-surgical spinal decompression therapy: does the scientific literature support
      efficacy claims made in the advertising media?
AB  - BACKGROUND: Traction therapy has been utilized in the treatment of low back pain
      for decades. The most recent incarnation of traction therapy is non-surgical
      spinal decompression therapy which can cost over $100,000. This form of therapy
      has been heavily marketed to manual therapy professions and subsequently to the
      consumer. The purpose of this paper is to initiate a debate pertaining to the
      relationship between marketing claims and the scientific literature on non
      surgical spinal decompression. DISCUSSION: Only one small randomized controlled
      trial and several lower level efficacy studies have been performed on spinal
      decompression therapy. In general the quality of these studies is questionable.
      Many of the studies were performed using the VAX-D unit which places the patient
      in a prone position. Often companies utilize this research for their marketing
      although their units place the patient in the supine position. SUMMARY: Only
      limited evidence is available to warrant the routine use of non-surgical spinal
      decompression, particularly when many other well investigated, less expensive
      alternatives are available.

PMID- 17511873
TI  - The school food environment and adolescent obesity: qualitative insights from
      high school principals and food service personnel.
AB  - OBJECTIVES: To examine high school personnel's perceptions of the school
      environment, its impact on obesity, and the potential impact of legislation
      regulating schools' food/beverage offerings. METHODS: Semi-structured interviews
      were conducted with the principal (n = 8) and dietitian/food service manager (n =
      7) at 8 schools (4 rural, 4 suburban) participating in a larger study examining
      the relationship between the school environment and adolescent health behavior
      patterns. RESULTS: Principal themes included: 1) Obesity is a problem in general,
      but not at their school, 2) Schools have been unfairly targeted above more
      salient factors (e.g., community and home environment), 3) Attempts at change
      should start before high school, 4) Student health is one priority area among
      multiple competing demands; academic achievement is the top priority, 5)
      Legislation should be informed by educators and better incorporate the school's
      perspective. Food service themes included: 1) Obesity is not a problem at their
      school; school food service is not the cause, 2) Food offerings are based largely
      on the importance of preparing students for the real world by providing choice
      and the need to maintain high participation rates; both healthy and unhealthy
      options are available, 3) A la carte keeps lunch participation high and prices
      low but should be used as a supplement, not a replacement, to the main meal, 4)
      Vending provides school's additional revenue; vending is not part of food service
      and is appropriate if it does not interfere with the lunch program. CONCLUSION:
      Discrepancies exist between government/public health officials and school
      personnel that may inhibit collaborative efforts to address obesity through
      modifications to the school environment. Future policy initiatives may be
      enhanced by seeking the input of school personnel, providing recommendations
      firmly grounded in evidence-based practice, framing initiatives in terms of their
      potential impact on the issues of most concern to schools (e.g., academic
      achievement, finances/revenue), and minimizing barriers by providing schools
      adequate resources to carry out and evaluate the effectiveness of their efforts.

PMID- 17511874
TI  - Evolution of rhodopsin ion pumps in haloarchaea.
AB  - BACKGROUND: The type 1 (microbial) rhodopsins are a diverse group of
      photochemically reactive proteins that display a broad yet patchy distribution
      among the three domains of life. Recent work indicates that this pattern is
      likely the result of lateral gene transfer (LGT) of rhodopsin genes between major
      lineages, and even across domain boundaries. Within the lineage in which the
      microbial rhodopsins were initially discovered, the haloarchaea, a similar patchy
      distribution is observed. In this initial study, we assess the roles of LGT and
      gene loss in the evolution of haloarchaeal rhodopsin ion pump genes, using
      phylogenetics and comparative genomics approaches. RESULTS: Mapping
      presence/absence of rhodopsins onto the phylogeny of the RNA polymerase B'
      subunit (RpoB') of the haloarchaea supports previous notions that rhodopsins are
      patchily distributed. The phylogeny for the bacteriorhodopsin (BR) protein
      revealed two discrepancies in comparison to the RpoB' marker, while the
      halorhodopsin (HR) tree showed incongruence to both markers. Comparative analyses
      of bacteriorhodopsin-linked regions of five haloarchaeal genomes supported
      relationships observed in the BR tree, and also identified two open reading
      frames (ORFs) that were more frequently linked to the bacteriorhodopsin gene than
      those genes previously shown to be important to the function and expression of
      BR. CONCLUSION: The evidence presented here reveals a complex evolutionary
      history for the haloarchaeal rhodopsins, with both LGT and gene loss contributing
      to the patchy distribution of rhodopsins within this group. Similarities between
      the BR and RpoB' phylogenies provide supportive evidence for the presence of
      bacteriorhodopsin in the last common ancestor of haloarchaea. Furthermore, two
      loci that we have designated bacterio-opsin associated chaperone (bac) and
      bacterio-opsin associated protein (bap) are inferred to have important roles in
      BR biogenesis based on frequent linkage and co-transfer with bacteriorhodopsin
      genes.

PMID- 17511875
TI  - Comparison of target labeling methods for use with Affymetrix GeneChips.
AB  - BACKGROUND: Several different commercial one-cycle labeling kits are available
      for preparation of the target for use with the Affymetrix GeneChip platform.
      However, there have been no evaluations of these different kits to determine if
      comparable results were generated. We report on the cRNA target synthesis,
      labeling efficiency and hybridization results using the One-Cycle Target Labeling
      Assay (Affymetrix), the BioArray RNA Amplification and Labeling System (Enzo Life
      Sciences), and the Superscript RNA Amplification System (Invitrogen Life
      Technologies). RESULTS: The only notable difference between kits was in the yield
      of cRNA target synthesized during in vitro transcription, where the BioArray
      assay had to be repeated several times in order to have sufficient target.
      However, each kit resulted in comparable signal and detection calls when
      hybridized to the Affymetrix GeneChip. CONCLUSION: These 3 one-cycle labeling
      kits produce comparable hybridization results. This provides users with several
      kit options and flexibility when using the Affymetrix system.

PMID- 17511877
TI  - National smokefree law in New Zealand improves air quality inside bars, pubs and
      restaurants.
AB  - BACKGROUND: We aimed to: (i) assess compliance with a new smokefree law in a
      range of hospitality settings; and (ii) to assess the impact of the new law by
      measuring air quality and making comparisons with air quality in outdoor smoking
      areas and with international data from hospitality settings. METHODS: We included
      34 pubs, restaurants and bars, 10 transportation settings, nine other indoor
      settings, six outdoor smoking areas of bars and restaurants, and six other
      outdoor settings. These were selected using a mix of random, convenience and
      purposeful sampling. The number of lit cigarettes among occupants at defined time
      points in each venue was observed and a portable real-time aerosol monitor was
      used to measure fine particulate levels (PM2.5). RESULTS: No smoking was observed
      during the data collection periods among over 3785 people present in the indoor
      venues, nor in any of the transportation settings. The levels of fine
      particulates were relatively low inside the bars, pubs and restaurants in the
      urban and rural settings (mean 30-minute level = 16 microg/m3 for 34 venues;
      range of mean levels for each category: 13 microg/m3 to 22 microg/m3). The
      results for other smokefree indoor settings (shops, offices etc) and for
      smokefree transportation settings (eg, buses, trains, etc) were even lower.
      However, some "outdoor" smoking areas attached to bars/restaurants had high
      levels of fine particulates, especially those that were partly enclosed (eg, up
      to a 30-minute mean value of 182 microg/m3 and a peak of maximum value of 284
      microg/m3). The latter are far above WHO guideline levels for 24-hour exposure
      (ie, 25 microg/m3). CONCLUSION: There was very high compliance with the new
      national smokefree law and this was also reflected by the relatively good indoor
      air quality in hospitality settings (compared to the "outdoor" smoking areas and
      the comparable settings in countries that permit indoor smoking). Nevertheless,
      adopting enhanced regulations (as used in various US and Canadian jurisdictions)
      may be needed to address hazardous air quality in relatively enclosed "outdoor"
      smoking areas.

PMID- 17511878
TI  - Age and gender differences of psychogenic fever: a review of the Japanese
      literature.
AB  - BACKGROUND: Psychogenic fever is one of the most common psychosomatic diseases.
      Patients with psychogenic fever have acute or persistent body temperature above
      normal range in psychologically stressful situations. In spite of numerous case
      reports on psychogenic fever, there are few epidemiological studies. Therefore,
      our goal was to investigate the age distribution and gender differences of
      psychogenic fever in Japan. METHODS: To achieve this goal, we searched Medline
      and Ichushi WEB, a Japanese medical database, and added other publications that
      were not included in these databases. Thus, we reviewed 195 Japanese cases of
      psychogenic fever published in 62 papers. RESULTS: Psychogenic fever patients
      ranged from 3 to 56 years old, with the highest number of cases occurring in 13
      year-olds in both sexes. The male: female ratio of 1: 1.19 suggested a slight
      predominance of female cases. Psychogenic fever accounted for 18% of fever cases
      of unknown origin in children and 2-6% of the psychosomatic diseases of pediatric
      patients. Patients with psychogenic fever were not only found in pediatrics
      departments, but also in psychosomatic medicine, psychiatry, internal medicine,
      anesthesiology, dentistry, and obstetrics/gynecology departments. CONCLUSION: The
      age of psychogenic fever patients ranged from 3 to 56 years old and the male:
      female ratio was 1:1.19. Psychogenic fever is seen especially in adolescence in
      Japan.

PMID- 17511876
TI  - Indole is an inter-species biofilm signal mediated by SdiA.
AB  - BACKGROUND: As a stationary phase signal, indole is secreted in large quantities
      into rich medium by Escherichia coli and has been shown to control several genes
      (e.g., astD, tnaB, gabT), multi-drug exporters, and the pathogenicity island of
      E. coli; however, its impact on biofilm formation has not been well-studied.
      RESULTS: Through a series of global transcriptome analyses, confocal microscopy,
      isogenic mutants, and dual-species biofilms, we show here that indole is a non
      toxic signal that controls E. coli biofilms by repressing motility, inducing the
      sensor of the quorum sensing signal autoinducer-1 (SdiA), and influencing acid
      resistance (e.g., hdeABD, gadABCEX). Isogenic mutants showed these associated
      proteins are directly related to biofilm formation (e.g., the sdiA mutation
      increased biofilm formation 50-fold), and SdiA-mediated transcription was shown
      to be influenced by indole. The reduction in motility due to indole addition
      results in the biofilm architecture changing from scattered towers to flat
      colonies. Additionally, there are 12-fold more E. coli cells in dual-species
      biofilms grown in the presence of Pseudomonas cells engineered to express toluene
      o-monooxygenase (TOM, which converts indole to an insoluble indigoid) than in
      biofilms with pseudomonads that do not express TOM due to a 22-fold reduction in
      extracellular indole. Also, indole stimulates biofilm formation in pseudomonads.
      Further evidence that the indole effects are mediated by SdiA and homoserine
      lactone quorum sensing is that the addition of N-butyryl-, N-hexanoyl-, and N
      octanoyl-L-homoserine lactones repress E. coli biofilm formation in the wild-type
      strain but not with the sdiA mutant. CONCLUSION: Indole is an interspecies signal
      that decreases E. coli biofilms through SdiA and increases those of pseudomonads.
      Indole may be manipulated to control biofilm formation by oxygenases of bacteria
      that do not synthesize it in a dual-species biofilm. Furthermore, E. coli changes
      its biofilm in response to signals it cannot synthesize (homoserine lactones),
      and pseudomonads respond to signals they do not synthesize (indole).

PMID- 17511879
TI  - The interaction of PP1 with BRCA1 and analysis of their expression in breast
      tumors.
AB  - BACKGROUND: The breast cancer susceptibility gene, BRCA1, is implicated in
      multiple cellular processes including DNA repair, the transactivation of genes,
      and the ubiquitination of proteins; however its precise functions remain to be
      fully understood. Identification and characterization of BRCA1 protein
      interactions may help to further elucidate the function and regulation of BRCA1.
      Additionally, detection of changes in the expression levels of BRCA1 and its
      interacting proteins in primary human breast tumors may further illuminate their
      role in the development of breast cancer. METHODS: We performed a yeast two
      hybrid study to identify proteins that interact with exon11 of BRCA1 and
      identified Protein Phosphatase 1beta (PP1beta), an isoform of the serine
      threonine phosphatase, PP1. GST-pull down and co-immunoprecipitation assays were
      performed to further characterize this interaction. Additionally, Real-Time PCR
      was utilized to determine the expression of BRCA1, PP1alpha, beta and gamma in
      primary human breast tumors and normal breast tissue to identify alterations in
      the expression of these genes in breast cancer. RESULTS: PP1 and BRCA1 co
      immunoprecipitate and the region within BRCA1 as well as the specific PP1
      interacting domain mediating this interaction were identified. Following mRNA
      expression analysis, we identified low levels of BRCA1 and variable levels of
      PP1alpha and beta in primary sporadic human breast tumors. Furthermore, BRCA1,
      PP1beta and PP1gamma were significantly higher in normal tissue specimens (BRCA1
      p = 0.01, PP1beta: p = 0.03, PP1gamma, p = 1.9 x 10(-6)) compared to sporadic
      breast tumor samples. Interestingly, we also identified that ER negative tumors
      are associated with low levels of PP1alpha expression. CONCLUSION: The
      identification and characterization of the interaction of BRCA1 with PP1 and
      detection of changes in the expression of PP1 and genes encoding other BRCA1
      associated proteins identifies important genetic pathways that may be significant
      to breast tumorigenesis. Alterations in the expression of genes, particularly
      phosphatases that operate in association with BRCA1, could negatively affect the
      function of BRCA1 or BRCA1 associated proteins, contributing to the development
      of breast cancer.

PMID- 17511880
TI  - Diagnostic value of harmonic transthoracic echocardiography in native valve
      infective endocarditis: comparison with transesophageal echocardiography.
AB  - BACKGROUND: Although echocardiography has been incorporated into the diagnostic
      algorithm of patients with suspected infective endocarditis (IE), systematic
      usage in clinical practice remains ill defined. To determine the diagnostic
      accuracy of detecting vegetations using harmonic transthoracic echocardiography
      (hTTE) as compared to transesophageal echocardiography (TEE) in patients with an
      intermediate likelihood of native valve IE. METHODS: Between 2004 and 2005, 36
      consecutive inpatients with an intermediate likelihood of disease were
      prospectively evaluated by hTTE and TEE. RESULTS: Of 36 patients (21 males with a
      mean age of 57 +/- 15 years, range 32 to 86 years), 19 patients had definite IE
      by TEE. The sensitivity for the detection of vegetations by hTTE was 84%,
      specificity of 88%, positive predictive value (PPV) of 89% and negative
      predictive value (NPV) of 82%. The association between hTTE and TTE
      interpretation for the presence and absence of vegetations were high (kappa =
      0.90 and 0.85 respectively). CONCLUSION: In patients with an intermediate
      likelihood of native valve IE, TTE with harmonic imaging provides diagnostic
      quality images in the majority of cases, has excellent concordance with TEE and
      should be recommended as the first line test.

PMID- 17511881
TI  - HER2 gene status in primary breast cancers and matched distant metastases.
AB  - INTRODUCTION: The status of the gene encoding human EGF-like receptor 2 (HER2) is
      an important prognostic and predictive marker in breast cancer. Only breast
      cancers with HER2 amplification respond to the targeted therapy with trastuzumab.
      It is controversial to what degree the primary tumour is representative of
      distant metastases in terms of HER2 status. Discrepancies in HER2 status between
      primary tumours and distant metastases have been described, but their reasons
      remain unclear. Here, we compared HER2 status on cytological specimens of distant
      metastases with the result from the primary carcinomas, and explored the
      prevalence of and the reasons for discrepant results. METHODS: HER2 status was
      determined by fluorescence in situ hybridisation. HER2 gene amplification was
      defined as a HER2/chromosome 17 signal ratio of 2 or more. HER2 results from
      cytological specimens of matched distant metastases were compared with the
      results from the corresponding primary tumours (n = 105 patients). In addition,
      lymph node metastases were analysed in 31 of these patients. RESULTS: HER2
      amplification was found in 20% of distant metastases. HER2 status was discordant
      between the primary tumour and distant metastasis in 7.6% of the 105 patients. Re
      evaluation revealed that in five patients (4.7%), discrepancies were due to
      interpretational difficulties. In two of these patients, focal amplification had
      initially been overlooked as a result of heterogeneity in the primary tumours or
      in the metastases, respectively. A further three patients had borderline
      amplification with a ratio close to 2. Discrepancy remained unexplained in three
      patients (2.9%). CONCLUSION: HER2 gene status remains highly conserved as breast
      cancers metastasise. However, discrepant results do occur because of
      interpretational difficulties and heterogeneity of HER2 amplification.
      Cytological specimens from distant metastases are well suited for HER2
      fluorescence in situ hybridisation analysis.

PMID- 17511882
TI  - Influences of different developmental periods of taurine supplements on synaptic
      plasticity in hippocampal CA1 area of rats following prenatal and perinatal lead
      exposure.
AB  - BACKGROUND: Previous study has demonstrated that dietary taurine supplement
      protected rats from impairments of synaptic plasticity induced by postnatal lead
      exposure. However, little is known about the role of taurine in the presence of
      prenatal and perinatal lead exposure. We investigated the possible effect of
      taurine supplement on prenatal and perinatal lead-induced synaptic plasticity
      deficit and determined developmental periods critical for the effect of taurine.
      RESULTS: In the present study, taurine was administrated to prenatal and
      perinatal lead-exposed rats in different developmental periods: from prenatal to
      weaning (Lead+PW-Tau), from weaning to life (Lead+WL-Tau), and from prenatal to
      life (Lead+PL-Tau). We examined the input-output (I/O) function, paired-pulse
      facilitation (PPF) and the long-term potentiation (LTP) of field excitatory
      postsynaptic potential (fEPSP) in the hippocampal CA1 area of rats on postnatal
      days 18-25 (P18-25) or days 60-75 (P60-75). We found that (1) on P18-25, taurine
      had no evident effect on I/O functions and PPF ratios of lead-exposed rats but
      caused a 12.0% increase in the LTP amplitudes of these animals; (2) on P60-75,
      taurine significantly elevated lead depressed I/O functions and PPF ratios in
      Lead+PW-Tau and Lead+PL-Tau rats, but failed in Lead+WL-Tau rats. The amplitudes
      of LTP of lead-exposed rats were all significantly increased by additional
      taurine supplement in any developmental period compared with untreated rats.
      Thus, taurine appeared to have the most effect during the prenatal and lactation
      periods and its effects on younger rats would not be manifest until the adult
      life; and (3) the level of lead deposition in hippocampus was evidently reduced
      by additional treatment of taurine in lead-exposed rats, compared with untreated
      rats. CONCLUSION: Taurine supplement can protect the adult rats from synaptic
      plasticity deficits following prenatal and perinatal lead exposure, and the
      protective effects are critical for the prenatal and lactation periods of lead
      exposed rats.

PMID- 17511883
TI  - The non-dosage compensated Lsp1alpha gene of Drosophila melanogaster escapes
      acetylation by MOF in larval fat body nuclei, but is flanked by two dosage
      compensated genes.
AB  - BACKGROUND: In Drosophila melanogaster dosage compensation of most X-linked genes
      is mediated by the male-specific lethal (MSL) complex, which includes MOF. MOF
      acetylates histone H4 at lysine 16 (H4K16ac). The X-linked Larval serum protein
      one alpha (Lsp1alpha) gene has long been known to be not dosage compensated. Here
      we have examined possible explanations for why the Lsp1alpha gene is not dosage
      compensated. RESULTS: Quantitative RNase protection analysis showed that the
      genes flanking Lsp1alpha are expressed equally in males and females and confirmed
      that Lsp1alpha is not dosage compensated. Unlike control X-linked genes,
      Lsp1alpha was not enriched for H4K16ac in the third instar larval fat body, the
      tissue in which the gene is actively expressed. X-linked Lsp1alpha promoter-lacZ
      reporter transgenes are enriched for H4K16ac in third instar larval fat body. An
      X-linked reporter gene bracketed by Lsp1alpha flanking regions was dosage
      compensated. One of the genes flanking Lsp1alpha is expressed in the same tissue.
      This gene shows a modest enrichment for H4K16ac but only at the part of the gene
      most distant from Lsp1alpha. Phylogenetic analyses of the sequences of the
      genomes of 12 Drosophila species shows that Lsp1alpha is only present within the
      melanogaster subgroup of species. CONCLUSION: Lsp1alpha is not modified by the
      MSL complex but is in a region of the X chromosome that is regulated by the MSL
      complex. The high activity or tissue-specificity of the Lsp1alpha promoter does
      not prevent regulation by the MSL complex. The regions flanking Lsp1alpha do not
      appear to block access by the MSL complex. Lsp1alpha appears to have recently
      evolved within the melanogaster subgroup of Drosophila species. The most likely
      explanation for why Lsp1alpha is not dosage compensated is that the gene has not
      evolved a mechanism to independently recruit the MSL complex, possibly because of
      its recent evolutionary origin, and because there appears to be a low level of
      bound MSL complex in a nearby gene that is active in the same tissue.

PMID- 17511884
TI  - Distinguishing enzymes using metabolome data for the hybrid dynamic/static
      method.
AB  - BACKGROUND: In the process of constructing a dynamic model of a metabolic
      pathway, a large number of parameters such as kinetic constants and initial
      metabolite concentrations are required. However, in many cases, experimental
      determination of these parameters is time-consuming. Therefore, for large-scale
      modelling, it is essential to develop a method that requires few experimental
      parameters. The hybrid dynamic/static (HDS) method is a combination of the
      conventional kinetic representation and metabolic flux analysis (MFA). Since no
      kinetic information is required in the static module, which consists of MFA, the
      HDS method may dramatically reduce the number of required parameters. However, no
      adequate method for developing a hybrid model from experimental data has been
      proposed. RESULTS: In this study, we develop a method for constructing hybrid
      models based on metabolome data. The method discriminates enzymes into static
      modules and dynamic modules using metabolite concentration time series data.
      Enzyme reaction rate time series were estimated from the metabolite concentration
      time series data and used to distinguish enzymes optimally for the dynamic and
      static modules. The method was applied to build hybrid models of two microbial
      central-carbon metabolism systems using simulation results from their dynamic
      models. CONCLUSION: A protocol to build a hybrid model using metabolome data and
      a minimal number of kinetic parameters has been developed. The proposed method
      was successfully applied to the strictly regulated central-carbon metabolism
      system, demonstrating the practical use of the HDS method, which is designed for
      computer modelling of metabolic systems.

PMID- 17511885
TI  - Risk factors for mediastinitis after cardiac surgery - a retrospective analysis
      of 1700 patients.
AB  - BACKGROUND: Mediastinitis is a rare, but serious complication of cardiac surgery.
      It has a significant socioeconomic impact and high morbidity. The purpose of this
      study was to determine pre-, intra-, and postoperative predictors of
      mediastinitis. METHODS AND RESULTS: In 1700 consecutive patients, who underwent
      cardiac surgery in 2001, 49 variables were retrospectively assessed. Forty-five
      patients (2.65%, 95% CI [1.88; 3.41]) developed postoperative mediastinitis. None
      of these patients died during their hospitalization. Multivariate analysis
      identified three of the 49 variables as highly significant independent predictors
      for the development of mediastinitis: obesity (OR 1.03, 95% CI [1.01; 1.04] p =
      0.001), chronic obstructive pulmonary disease (OR 3.30, 95% CI [1.58; 6.88], p =
      0.001), and bilateral grafting of the internal mammary artery (OR 3.18, 95% CI
      [1.20; 8.43] p = 0.02). The model is reliable in terms of its goodness of fit, it
      also discriminates well. Additionally, univariate analysis identified diabetes
      mellitus, CCS class and the number of intraoperatively transfused units of fresh
      frozen plasma as variables with a significant impact. CONCLUSION: The present
      study suggests that bilateral IMA grafting, chronic obstructive pulmonary disease
      and obesity are important predictors of mediastinitis.

PMID- 17511887
TI  - Alendronate increases BMD at appendicular and axial skeletons in patients with
      established osteoporosis.
AB  - BACKGROUND: To identify high-risk patients and provide pharmacological treatment
      is one of the effective approaches in prevention of osteoporotic fractures. This
      study investigated the effect of 12-month Alendronate treatment on bone mineral
      density (BMD) and bone turnover biochemical markers in postmenopausal women with
      one or more non-traumatic fractures, i.e. patients with established osteoporosis.
      METHODS: A total of 118 Hong Kong postmenopausal Chinese women aged 50 to 75 with
      low-energy fracture at distal radius (Colles' fracture) were recruited for BMD
      measurement at lumbar spine and non-dominant hip using Dual-Energy X-ray
      Absorptiometry (DXA). 47 women with BMD T-score below -2 SD at either side were
      identified as patients with established osteoporosis and then randomized into
      Alendronate group (n = 22) and placebo control group (n = 25) for BMD measurement
      at spine and hip using DXA and distal radius of the non-fracture side by
      peripheral quantitative computed tomography (pQCT), and bone turnover markers,
      including bone forming alkaline phosphatase (BALP) and bone resorbing urinary
      Deoxypyridinoline (DPD). All measurements were repeated at 6 and 12 months.
      RESULTS: Alendronate treatment significantly increased BMD, more in weight
      bearing skeletons (5.1% at spine and 2.5% at hip) than in non-weight bearing
      skeleton (0.9% at distal radius) after 12 months treatment. Spine T-score was
      significant improved in Alendronate group (p < 0.01) (from -2.2 to -1.9) but not
      in control placebo group. The Alendronate treatment effect was explained by
      significant suppression of bone turnover. CONCLUSION: 12 months Alendronate
      treatment was effective to increase BMD at both axial and appendicular skeletons
      in postmenopausal women with established osteoporosis.

PMID- 17511886
TI  - Down-regulation of human topoisomerase IIalpha expression correlates with
      relative amounts of specificity factors Sp1 and Sp3 bound at proximal and distal
      promoter regions.
AB  - BACKGROUND: Topoisomerase IIalpha has been shown to be down-regulated in
      doxorubicin-resistant cell lines. The specificity proteins Sp1 and Sp3 have been
      implicated in regulation of topoisomerase IIalpha transcription, although the
      mechanism by which they regulate expression is not fully understood. Sp1 has been
      shown to bind specifically to both proximal and distal GC elements of the human
      topoisomerase IIalpha promoter in vitro, while Sp3 binds only to the distal GC
      element unless additional flanking sequences are included. While Sp1 is thought
      to be an activator of human topoisomerase IIalpha, the functional significance of
      Sp3 binding is not known. Therefore, we sought to determine the functional
      relationship between Sp1 and Sp3 binding to the topoisomerase IIalpha promoter in
      vivo. We investigated endogenous levels of Sp1, Sp3 and topoisomerase IIalpha as
      well as binding of both Sp1 and Sp3 to the GC boxes of the topoisomerase IIalpha
      promoter in breast cancer cell lines in vivo after short term doxorubicin
      exposure. RESULTS: Functional effects of Sp1 and Sp3 were studied using transient
      cotransfection assays using a topoisomerase IIalpha promoter reporter construct.
      The in vivo interactions of Sp1 and Sp3 with the GC elements of the topoisomerase
      IIalpha promoter were studied in doxorubicin-treated breast cancer cell lines
      using chromatin immunoprecipitation assays. Relative amounts of endogenous
      proteins were measured using immunoblotting. In vivo DNA looping mediated by
      proteins bound at the GC1 and GC2 elements was studied using the chromatin
      conformation capture assay. Both Sp1 and Sp3 bound to the GC1 and GC2 regions.
      Sp1 and Sp3 were transcriptional activators and repressors respectively, with Sp3
      repression being dominant over Sp1-mediated activation. The GC1 and GC2 elements
      are linked in vivo to form a loop, thus bringing distal regulatory elements and
      their cognate transcription factors into close proximity with the transcription
      start site. CONCLUSION: These observations provide a mechanistic explanation for
      the modulation of topoisomerase IIalpha and concomitant down-regulation that can
      be mediated by topoisomerase II poisons. Competition between Sp1 and Sp3 for the
      same cognate DNA would result in activation or repression depending on absolute
      amounts of each transcription factor in cells treated with doxorubicin.

PMID- 17511888
TI  - Femoral tunnel placement in anterior cruciate ligament reconstruction: rationale
      of the two incision technique.
AB  - Endoscopic anterior cruciate ligament (ACL) reconstruction can be performed
      through one-incision or two-incision technique. The current one-incision
      endoscopic ACL single bundle reconstruction techniques attempt to perform an
      isometric repair placing the graft along the roof of the intercondylar notch,
      anterior and superior to the native ACL insertion. However the ACL isometry is a
      theoretical condition, and has not stood up to detailed testing and
      investigation. Moreover this type of reconstruction results in a vertically
      oriented non-anatomic graft, which is able to control anterior tibial translation
      but not the rotational component of the instability. Femoral tunnel obliquity has
      a great effect on rotational stability. To improve the obliquity of graft, an
      anatomical ACL reconstruction should be attempt. Anatomical insertion of ACL on
      the femur lies very low in the notch, spreading between 11 and 9-8 o'clock
      position and the center lies lower than at 11 o'clock position. Femoral aiming
      devices through the tibial tunnel aim at an isometric placement, and they do not
      aim at an anatomic position of the graft. Also, a placement of tunnel in a
      position of 11 o'clock is unable to restore rotational stability. The two
      incision technique, with the possibility to position femoral tunnel independently
      by tibial tunnel, allows us to place femoral tunnel entrance in a position of 10
      'clock that can most accurately reproduce the anatomic behaviour of the ACL and
      can potentially improve the response of the graft to rotatory loads. This
      positioning results in a more oblique graft placement, avoiding problem related
      to PCL impingement during knee flexion. Further studies are required to
      understand if this kind of reconstruction can ameliorate proprioception as well
      as clinical outcome at a long-term follow-up.

PMID- 17511889
TI  - Serotonin transporter binding of [123I]ADAM in bulimic women, their healthy twin
      sisters, and healthy women: a SPET study.
AB  - BACKGROUND: Bulimia Nervosa (BN) is believed to be caused by an interaction of
      genetic and environmental factors. Previous studies support the existence of a
      bulimia-related endophenotype as well as disturbances in serotonin (5-HT)
      transmission. We studied serotonin transporter (SERT) binding in BN, and to
      investigate the possibility of a SERT-related endophenotype for BN, did this in a
      sample of female twins. We hypothesized clearly reduced SERT binding in BN women
      as opposed to healthy women, and intermediate SERT binding in unaffected co
      twins. METHODS: We studied 13 female twins with BN (9 with purging and 4 with non
      purging BN) and 25 healthy women, including 6 healthy twin sisters of BN patients
      and 19 women from 10 healthy twin pairs. [123I]ADAM, a selective SERT radioligand
      for single photon emission tomography (SPET) imaging, was used to assess SERT
      availability in the midbrain and the thalamus. RESULTS: No differences in SERT
      binding were evident when comparing the BN women, their unaffected co-twins and
      the healthy controls (p = 0.14). The healthy sisters of the BN patients and the
      healthy control women had similar SERT binding in both brain regions. In a post
      hoc subgroup analysis, the purging bulimics had higher SERT binding than the
      healthy women in the midbrain (p = 0.03), but not in the thalamus. CONCLUSION:
      Our finding of increased SERT binding in the midbrain in the purging BN women
      raises the possibility that this subgroup of bulimics might differ in
      serotonergic function from the non-purging ones. The similarity of the unaffected
      co-twins and the healthy controls doesn't support our initial assumption of a
      SERT-related endophenotype for BN. Due to the small sample size, our results need
      to be interpreted with caution and verified in a larger sample.

PMID- 17511890
TI  - Rad9 modulates the P21WAF1 pathway by direct association with p53.
AB  - BACKGROUND: Previous studies suggest that human RAD9 (hRad9), encoding a DNA
      damage checkpoint molecule, which is frequently amplified in epithelial tumor
      cells of breast, lung, head and neck cancer, participates in regulation of the
      tumor suppressor p53-dependent transactivation of pro-survival P21WAF1. This
      study examined the exact mechanism of the hRad9 function, especially through the
      phosphorylation of the C-terminus, in the transcription regulation of P21WAF1.
      RESULTS: The transfection of phosphorylation-defective hRAD9 mutants of C
      terminus resulted in reduction of the p53-dependent P21WAF1 transactivation; the
      knockdown of total hRad9 elicited an increased P21WAF1 mRNA expression.
      Immunoprecipitation and a ChIP assay showed that hRad9 and p53 formed a complex
      and both were associated with two p53-consensus DNA-binding sequences in the 5'
      region of P21WAF1 gene. The association was reduced in the experiment of
      phosphorylation-defective hRAD9 mutants. CONCLUSION: The present study indicates
      the direct involvement of hRad9 in the p53-dependent P21WAF1 transcriptional
      mechanism, presumably via the phosphorylation sites, and alterations of the hRad9
      pathway might therefore contribute to the perturbation of checkpoint activation
      in cancer cells.

PMID- 17511891
TI  - Parents' attitudes towards hepatitis B vaccination for their children. A survey
      comparing paper and web questionnaires, Sweden 2005.
AB  - BACKGROUND: The World Health Organisation, WHO, recommends that most countries
      should vaccinate all children against hepatitis B. Sweden has chosen not to do
      so, but the issue is reassessed regularly. The objective of this survey was to
      assess knowledge and attitudes towards hepatitis B vaccine for children among
      parents living in Sweden, and to compare distribution of responses and response
      rate between parents answering a postal questionnaire and those responding via
      the Internet. METHODS: A population-based cross-sectional survey, where the
      sampling frame consisted of all parents to a child born 2002 living in Sweden.
      Two independent samples of 1001 parents in each sample were drawn. All parents
      were contacted by postal mail. The parents in the first sample were invited to
      participate by answering a paper questionnaire. The parents in the second sample
      were given an individual user name along with a password, and asked to log on to
      the Internet to answer an identical electronic questionnaire. RESULTS: A total of
      1229 questionnaires were analysed. The overall response rate for paper
      questionnaires was 55%, and 15% for the web version. Knowledge of the disease
      hepatitis B was overall high (90%). A higher degree of knowledge was seen among
      parents with education beyond high school (p = 0.001). This group of parents also
      had a higher tendency to reply via the Internet (p = 0.001). The willingness to
      accept hepatitis B vaccine for their child was correlated to the acceptance of
      the present childhood vaccination programme (p = 0.001). CONCLUSION: The results
      reveal a high level of knowledge of the disease and a positive attitude to having
      their children vaccinated. This study also displays that the conventional postal
      method of surveying still delivers a higher response rate than a web-based
      survey.

PMID- 17511892
TI  - Powell's pearls: Richard Wesley TeLinde, MD (1894-1985).

PMID- 17511894
TI  - Puerperal Pyrexia: a review. Part II.
AB  - Puerperal pyrexia and sepsis are among the leading causes of preventable maternal
      morbidity and mortality not only in developing countries but in developed
      countries as well. Most postpartum infections take place after hospital
      discharge, which is usually 24 hours after delivery. In the absence of postnatal
      follow-up, as is the case in many developing countries, many cases of puerperal
      infections can go undiagnosed and unreported. Besides endometritis
      (endomyometritis or endomyoparametritis), wound infection, mastitis, urinary
      tract infection, and septic thrombophlebitis are the chief causes of puerperal
      infections. The predisposing factors leading to the development of sepsis include
      home birth in unhygienic conditions, low socioeconomic status, poor nutrition,
      primiparity, anemia, prolonged rupture of membranes, prolonged labor, multiple
      vaginal examinations in labor, cesarean section, obstetrical maneuvers, retained
      secundines within the uterus and postpartum hemorrhage. Maternal complications
      include septicemia, endotoxic shock, peritonitis or abscess formation leading to
      surgery and compromised future fertility. The transmissions of infecting
      organisms are typically categorized into nosocomial, exogenous, and endogenous.
      Nosocomial infections are acquired in hospitals or other health facilities and
      may come from the hospital environment or from the patient's own flora. Exogenous
      infections come from external contamination, especially when deliveries take
      place under unhygienic conditions. Endogenous organisms, consisting of mixed
      flora colonizing the woman's own genital tract, are also a source of infection in
      puerperal sepsis. Aseptic precautions, advances in investigative tools and the
      use of antibiotics have played a major role in reducing the incidence of
      puerperal infections. Part II of this review describes the best management of
      wound infection, pelvic abscess, episiotomy infection, thrombophlebitis,
      mastitis, urinary tract infection, and miscellaneous infections. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians Learning Objectives: After
      completion of this article, the reader should be able to recall that world wide
      puerperal sepsis is a leading cause of maternal mortality, state that many of the
      predisposing factors are preventable, explain that both nosocomial infections as
      well as exogenous infections are serious factors, and relate that septic
      techniques and antibiotics can play a major role in reducing the incidence of
      puerperal infections.

PMID- 17511893
TI  - Puerperal pyrexia: a review. Part I.
AB  - Puerperal pyrexia and sepsis are among the leading causes of preventable maternal
      morbidity and mortality not only in developing countries but in developed
      countries as well. Most postpartum infections take place after hospital
      discharge, which is usually 24 hours after delivery. In the absence of postnatal
      follow-up, as is the case in many developing countries, many cases of puerperal
      infections can go undiagnosed and unreported. Besides endometritis
      (endomyometritis or endomyoparametritis), wound infection, mastitis, urinary
      tract infection, and septic thrombophlebitis are the chief causes of puerperal
      infections. The predisposing factors leading to the development of sepsis include
      home birth in unhygienic conditions, low socioeconomic status, poor nutrition,
      primiparity, anemia, prolonged rupture of membranes, prolonged labor, multiple
      vaginal examinations in labor, cesarean section, obstetrical maneuvers, retained
      secundines within the uterus and postpartum hemorrhage. Maternal complications
      include septicemia, endotoxic shock, peritonitis or abscess formation leading to
      surgery and compromised future fertility. The transmissions of infecting
      organisms are typically categorized into nosocomial, exogenous, and endogenous.
      Nosocomial infections are acquired in hospitals or other health facilities and
      may come from the hospital environment or from the patient's own flora. Exogenous
      infections come from external contamination, especially when deliveries take
      place under unhygienic conditions. Endogenous organisms, consisting of mixed
      flora colonizing the woman's own genital tract, are also a source of infection in
      puerperal sepsis. Aseptic precautions, advances in investigative tools and the
      use of antibiotics have played a major role in reducing the incidence of
      puerperal infections. Part I of this review provides background information and
      definitions, discusses the incidence and risk factors, explains the microbiology
      and pathophysiology of various infections, and delineates the signs and symptoms
      of major puerperal infection. TARGET AUDIENCE: Obstetricians & Gynecologists,
      Family Physicians Learning Objectives: After completion of this article, the
      reader should be able to recall that world wide puerperal sepsis is a leading
      cause of maternal mortality, state that many of the predisposing factors are
      preventable, explain that both nosocomial infections as well as exogenous
      infections are serious factors, and relate that septic techniques and antibiotics
      can play a major role in reducing the incidence of puerperal infections.

PMID- 17511895
TI  - Update on the use of bisphosphonates in the management of postmenopausal
      osteoporosis by obstetricians-gynecologists.
AB  - Obstetricians-gynecologists often have a special and long-term relationship with
      their patients and are ideally placed to assess their fracture risk and to
      institute appropriate therapy for osteoporosis. Assessment of risk factors
      according to the World Health Organization and more recent guidelines (e.g., age,
      smoking history, previous fracture, parental fracture, corticosteroid use,
      weight) enables the clinician to target patients for testing of bone mineral
      density by techniques such as dual-energy x-ray absorptiometry at the proximal
      femur. The current therapy of choice is an oral bisphosphonate, which has proven
      efficacy in increasing bone mineral density, reducing bone-turnover markers, and
      reducing fracture rates. Their main drawback is inconvenient dosing requirements,
      which necessitates taking the drug in the morning at least 30 minutes before the
      first meal or drink of the day; this may contribute to poor adherence with
      therapy and suboptimal outcomes. The availability of daily or weekly (alendronate
      and risedronate) or monthly (ibandronate) bisphosphonates means that patients can
      have therapy at their preferred frequency, and along with education regarding
      lifestyle issues such as nutrition, exercise, smoking, and alcohol use, and
      measures to reduce tripping in the home, should reduce the prevalence of
      osteoporotic fractures. TARGET AUDIENCE: Obstetricians & Gynecologists, Family
      Physicians Learning Objectives: After completion of this article, the reader
      should be able to recall that there are high-risk fracture patients, explain that
      Ob/Gyn physicians should target their diagnostic and treatment options to these
      patients, and state that there are ways that increase compliance to recommended
      bisphosphonates in addition to the recommended lifestyle changes.

PMID- 17511896
TI  - The NIH MRI study of normal brain development: performance of a population based
      sample of healthy children aged 6 to 18 years on a neuropsychological battery.
AB  - The National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of
      Normal Brain Development is a landmark study in which structural and metabolic
      brain development and behavior are followed longitudinally from birth to young
      adulthood in a population-based sample of healthy children. The
      neuropsychological assessment protocol for children aged 6 to 18 years is
      described and normative data are presented for participants in that age range (N
      = 385). For many measures, raw score performance improved steeply from 6 to 10
      years, decelerating during adolescence. Sex differences were documented for Block
      Design (male advantage), CVLT, Pegboard and Coding (female advantage). Household
      income predicted IQ and achievement, as well as externalizing problems and social
      competence, but not the other cognitive or behavioral measures. Performance of
      this healthy sample was generally better than published norms. This linked
      imaging-clinical/behavioral database will be an invaluable public resource for
      researchers for many years to come.

PMID- 17511897
TI  - Distinct roles of CaM and Ca(2+)/CaM -dependent protein kinase II in Ca(2+) 
      dependent facilitation and inactivation of cardiac L-type Ca(2+) channels.
AB  - L-type Ca(2+) channels have two opposing forms of autoregulatory feedback, Ca(2+)
      -dependent facilitation (CDF) and Ca(2+) -dependent inactivation (CDI), in
      response to increases in intracellular Ca(2+) concentration. Calmodulin (CaM) has
      been reported to mediate the two feedbacks. Although both the direct binding of
      CaM and the phosphorylation mediated by Ca(2+)/CaM -dependent protein kinase II
      (CaMKII) have been suggested as underlying mechanisms, the detailed features
      remain to be clarified. In this study, we investigated the effects of CaM and
      CaMKII inhibitors on CDF and CDI with patch clamp cell-attached recordings in
      guinea-pig ventricular myocytes. We confirmed that a high-K(+) and high-Ca(2)(+)
      could induce an increase of the intracellular Ca(2+) concentration and subsequent
      CDF and CDI. We then found that CDF and CDI were both depressed and were finally
      abolished by treatment with a CaM inhibitor chlorpromazine (1-100 microM) in a
      concentration-dependent manner. Another CaM antagonist calmidazolium (1 microM)
      showed a similar effect. In contrast, CaMKII inhibitors, KN-62 (0.1-3 microM) and
      autocamtide 2 -related inhibitory peptide (1 microM), delayed the development of
      CDF and CDI significantly, but they did not depress either CDF or CDI. These
      results imply that CaM is necessary and possibly sufficient for the two
      mechanisms. We propose a hypothesis that CaM is a key molecule to bifurcate the
      Ca(2+) signal to CDF and CDI and that CaMKII plays a modulatory role in them
      both.

PMID- 17511898
TI  - [Pain or pains: a new paradigm].

PMID- 17511899
TI  - [Rate of traumatic retinal injuries requiring urgent care. Is ocular fundus
      evaluation essential in the emergency room?].
AB  - BACKGROUND: A high rate of traumatic retinal injuries does not require a directed
      ocular fundus evaluation but those that deserve urgent care need it. The rate of
      traumatic retinal injuries that require urgent care was identified in order to
      learn whether there is a need of evaluating the ocular fundus in an emergency
      room. METHODS: Patients with ocular trauma and ocular fundus evaluation who were
      referred to an Ophthalmology Service of a general hospital were included;
      patients with superficial foreign bodies were excluded. The rate of injuries that
      require urgent care (retinal detachment, intraocular foreign body) was identified
      and 95% confidence intervals (CI) were calculated. RESULTS: One hundred fifty
      three eyes of 148 patients (age 3-74 years, mean 26.4 years) were examined. Of 75
      retinal injuries, 7 required urgent care (4.6%, 95% CI 1.3-7.9); the rate was
      0.8% in closed globe trauma (95% CI 0-2.37) and 20.7 in open globe trauma (95% CI
      5.9-35.5). CONCLUSIONS: According to the rate of retinal injuries that would
      require urgent care in similar groups, in closed-globe trauma ocular fundus
      evaluation in the Emergency Room could be substituted by the evaluation of the
      fundus reflex; findings of any of these injuries in open-globe trauma does not
      modify the initial approach.

PMID- 17511900
TI  - [The extent of surgery for well-differentiated thyroid cancer related with
      surgical morbidity].
AB  - BACKGROUND: The extent of surgical treatment for well-differentiated thyroid
      cancer is based on non-oncological reasons related to morbidity and oncological
      reasons related to risk factors and cancer staging. We undertook this study to
      evaluate if the surgical extent for the treatment of well-differentiated thyroid
      cancer has a relationship with increased morbidity. METHODS: A cross-sectional,
      comparative, retrospective study was conducted in 823 thyroidectomies done over 5
      years with systematized surgical technique. Subjects were grouped in two groups:
      G1 with differentiated thyroid cancer; G2 with benign thyroid disease. Studied
      variables were definitive hypocalcemia (DH), recurrent laryngeal nerve lesion
      (RLN) and external branch of superior laryngeal nerve lesion (EBSLN). Variables
      were measured 6 months after surgery and evaluation was also done as to the
      training of the surgeon: expert vs. surgical resident. Statistical analysis was
      done by central tendency measures and chi(2), with p >0.05 as significant.
      RESULTS: We studied 766 women and 57 men with an average age of 42 years (range:
      16-89 years). In G1 there were 195 cases all with total thyroidectomies (TT), 4
      (2.05%) DH, 2 (1.02%) RLN, 3 (1.53%) EBSLN. In 45 cases, surgery was performed by
      the resident. G2 included 628 cases, 56 TT and 572 unilateral hemithyroidectomies
      with 7 (1.1%) DH, 9 (1.43%) RLN and 3 (0.47%) EBSLN. In 134 cases, surgery was
      performed by the resident. Comparing these results, no differences were
      documented in terms of cancer diagnosis and who performed the surgery, expert
      surgeon or surgical resident (p >0.05). CONCLUSIONS: There is no reason to limit
      the extent of surgery for treatment of well-differentiated thyroid cancer, based
      on morbidity.

PMID- 17511901
TI  - [Splenectomy in autoimmune hematological diseases. Comparative study between
      laparoscopic and open technique].
AB  - BACKGROUND: We undertook this study to compare the outcome of laparoscopic and
      open splenectomy in the treatment of hematological diseases. METHODS: This was a
      comparative study of two groups of patients. The study sample consisted of 37
      patients divided into two groups: group I, open splenectomy (OS) and group II,
      laparoscopic splenectomy (LS). Twenty one consecutive patients with LS were
      compared to 16 randomized patients selected from clinical records of OS patients.
      General and specific variables were collected in Microsoft Access database and
      analyzed in SPSS for Windows statistical program. Statistical analysis was done.
      RESULTS: Of 25 women and 12 men (37.2 +/- 16.9 years old), 6 had autoimmune
      hemolytic anemia, 29 idiopathic thrombocytopenic purpura (ITP), and two had Evans
      syndrome. Patients with ITP had preoperative platelet count of 74.6 +/-
      64.1/mm(3) and patients with autoimmune hemolytic anemia had a preoperative
      hemoglobin of 10.6 +/- 2.9 g/dl. Ten patients had co-morbidity. There were 16 OS
      and 21 LS. Size of spleen was 13.1 +/- 3.7 cm and weight was 178 +/- 115 g.
      Surgical time for OS was 69.3 +/- 21.7 min and for LS was 152.8 +/- 61.1 min (p
      <0.05). Operative bleeding for OS was 300 +/- 265 ml and for LS it was 265 +/-
      198 ml (p >0.05). One patient in LS group had red cell transfusion and two in the
      same group had to be converted to OS to reassure hemostasis. Reoperations had to
      be done in the OS group, two to control bleeding and one with a left lobe hepatic
      hematoma. There was no mortality. Postoperative platelet count in patients with
      ITP increased to 246 +/- 159 and hemoglobin in patients with hemolytic anemia
      increased to 12.1 +/- 3.6 g (p <0.05). Hospital stay in OS was 5.06 +/- 3.6 days
      vs. 2.06 +/- 0.26 in LS (p <0.05). Patients in OS had 30.6 +/- 10.5 lost work
      days vs. 15.5 +/- 4.6 in LS group (p <0.05). CONCLUSIONS: It is possible to treat
      patients with hematological diseases with LS. LS is time-consuming compared to
      OS. Morbidity in LS may be less than in OS. Mortality may be zero. Hospital stay
      and postoperative lost work days are less in LS than with OS. LS may be the gold
      standard in treatment of patients with hematological diseases.

PMID- 17511902
TI  - [Malignant germ cell ovarian tumors: clinical characteristics, treatment and
      outcome].
AB  - BACKGROUND: Ovarian malignant neoplasms in young girls and teenagers are unusual.
      The most frequent histological subtypes found are those derived from germ cells.
      The biological course of this heterogeneous group of neoplasm is unpredictable.
      The main clinical symptom is chronic abdominal pain and palpable abdominal tumor.
      Treatment has been improved with combined modality therapy. We present treatment
      results of the germ cell subtype of malignant ovarian tumors. METHODS: A
      retrospective review was performed from the medical records of 16 ovarian germ
      cell patients in order to analyze clinical characteristics, type of surgery
      performed and chemotherapy, as well as final treatment results. RESULTS: Mean age
      was 13.8 years, and the left ovary was affected in 75% of cases. The most
      frequent histological subtype was dysgerminoma (56%). Stage distribution was as
      follows: stage I, one patient diagnosed with choriocarcinoma; stage II, three
      cases (19%); stage III, 10 cases; and 2 cases in stage IV. Biopsy was performed
      in 70% of cases. Mean number of chemotherapy cycles (cisplatin, etoposide and
      bleomycin) was 4, and 85% of patients survived >2 years. CONCLUSIONS: Surgical
      procedure was conservative and a favorable outcome was observed for the
      chemotherapy cycles.

PMID- 17511903
TI  - [Lymphatic mapping and sentinel node biopsy in penis cancer. Feasibility study
      and preliminary report].
AB  - Most patients with invasive squamous cell carcinoma of the penis do not have
      inguinal node metastasis at the time of diagnosis and 50% of those having
      palpable nodes are inflammatory. Penis cancer (PC) treatment implies resection of
      the primary tumor and inguinal lymphadenectomy; nevertheless, morbidity related
      to this procedure is high and its usefulness may be questioned in patients
      without metastasis in dissected nodes. Lymphatic mapping with sentinel node
      biopsy (LMSNB) is a valid alternative, useful in other neoplasias. The objective
      of this study is to determine if it is possible to identify a sentinel node (SN)
      in patients with PC. Patients with T1-2 PC without palpable nodes (N0) were
      included. LMSNB was carried out with the combined technique (blue dye and
      radiocolloid). All patients underwent an elective bilateral inguinal
      lymphadenectomy. Sensitivity and false negative index were calculated. SNs were
      sent for transoperative study with imprint technique and, definitively, with
      serial cuts and hematoxylin/eosin staining. Nine patients showed results with 32
      lymph carrier zones and SN was identified in all of them, 4 regions had
      metastasis, in 3 the SN was metastatic and in one patient was metastasis-negative
      (false negative); sensitivity = 80%; false negatives index = 20%. Seven patients
      (77%) did not have node metastasis. LMSNB is an alternative for staging PC
      patients and could prevent unnecessary inguinal lymphadenectomies. A larger
      number of patients is required to validate the sturdy. The combined technique
      offers a high rate of success in SN identification.

PMID- 17511904
TI  - [Surgical treatment for scoliosis. Minimal evolution control at 5 years].
AB  - BACKGROUND: We undertook this study to determine the surgical treatments results
      performed often to correct scoliosis in the Spinal Surgery Service in the
      INR/Orthopedics (National Institute of Rehabilitation/Orthopedics), Mexico City.
      METHODS: We conducted a longitudinal, prospective, descriptive, and clinical
      study with a deliberated intervention controlled from a historical cohort. One
      hundred twenty patients with scoliosis were reviewed in whom surgery was
      performed during 1990-1999. For quantitative variables, pre- vs. postoperative
      measures were compared using non-parametric means with chi(2) or in this case
      with ANOVA by Kruskall-Wallis test. Differences are considered significant if p
      <0.05. RESULTS: Age average of patients was 12 years. There were 75 females and
      45 males. There were 59 idiopathic scoliosis cases and 54 congenital scoliosis
      cases. Anterior approach was accomplished in 61 cases with posterior fixation.
      Posterior approach was used in 54 cases. There were 76 cases of Luque segmental
      instrumentation. Pre-operatively, scoliosis was ranked (18 to 110 grades) and
      postoperatively (5 to 90 grades) (p = 0.00001). There were 21 complications, 9
      due to injuries or infection. In 76 patients, different fixation techniques were
      used, obtaining a correction average of 14.47 grades. Forty four patients were
      structured with bars, four distal screws, two compression screws, proximal hooks
      with sublaminar wire, and the angle was reduced on average 23.11 grades.
      CONCLUSIONS. Average reduction of scoliosis was higher with the modified Luque
      III instrumentation (p <0.045). There was no difference between etiology and
      preoperative angle.

PMID- 17511905
TI  - [Comparison of two types of anesthesia on plasma levels of inflammatory markers].
AB  - BACKGROUND: The aim of this work was to determine and compare plasma levels of
      proinflammatory cytokines (IL-1beta, IL-6 and TNF-alpha), C-reactive protein
      (CRP) and lipoperoxides in patients submitted to laparoscopic cholecystectomy
      under general anesthesia or regional anesthesia. METHODS: Two groups of 15
      patients of both sexes were submitted to laparoscopic cholecystectomy either with
      general or regional anesthesia. In all cases we obtained three samples of plasma.
      The first sample was collected immediately before surgery, whereas the other
      samples were collected 60 min and 24 h after the cholecystectomy. Using
      commercial kits, plasma levels of IL-1beta, IL-6 and TNF-alpha were quantified by
      ELISA, whereas lipoperoxides were determined by a colorimetric method. The
      ultrasensitive CRP was determined in the hospital by the Prestige 24I automated
      method. RESULTS: In all determinations, proinflammatory cytokines increased 24 h
      after surgery except plasma levels of IL-1beta in the regional anesthesia group.
      Comparison of the two different groups showed that the general anesthesia group
      had a similar or higher quantity of proinflammatory cytokines and oxidative
      stress when compared to the regional anesthesia group (p <0.05). In contrast,
      plasma levels of CRP were lower in the general anesthesia group (p <0.005).
      CONCLUSIONS: The type of anesthesia influences in a different manner the
      secretion of soluble mediators of inflammation. These observations may have
      important clinical repercussions.

PMID- 17511906
TI  - [Unipedal stance time and fall risk in the elderly].
AB  - BACKGROUND: We undertook this study to relate unipodal stance time (UST) as a
      falls indicator in the elderly and to corroborate with UST exercise increments.
      METHODS: One hundred sixty eight elderly subjects (age >70 years) with two or
      more falls during the previous 12 months were compared with 150 similar subjects
      without falls. UST chronometry and quadriceps and triceps brachialis strength
      dynamometry were used. Equilibrium and antigravity muscle-strengthening exercise
      program with 20 work sessions were carried out. Results were analyzed with
      chi(2), Student's t-test, and Fisher tests. RESULTS: UST of the control group
      showed 28.84 +/- 4.73 sec (mean +/- SD). The UST sample showed 19.18 +/- 4.24
      sec. The test was initially impossible to carry out in 42 cases (p = 0.05). The
      final evaluation showed 142 cases with 30 sec of UST (p = 0.00001), isometric
      force increased in 70% and 30%, respectively (p = 0.05). At 6-month follow-up, 53
      falls were reported, 29 were in patients who could not accomplish UST measurement
      on initial evaluation. CONCLUSIONS: UST <30 sec is an indicator of falls in
      elderly people, and exercise programs increase UST.

PMID- 17511907
TI  - [Penile calciphylaxis: case report and literature review].
AB  - BACKGROUND: Calciphylaxis is a serious condition characterized by ischemic
      ulceration of the skin and necrosis secondary to dystrophic calcification of the
      subcutaneous tissue and small arteries. It affects primarily patients with end
      stage renal disease with prevalence up to 4%. However, penile calciphylaxis has
      been reported in only 37 cases in the international literature. We report one
      case, to review the literature and to provide the basis for a rational treatment
      of calciphylaxis of the penis that reduces the associated mortality. CASE REPORT:
      We report the case of an 82-year-old male with a 15-year history of type 2
      diabetes mellitus and renal insufficiency during the past 2 years. He presented
      an increase of consistency of the distal portion in the penis' glans and scrotal
      swelling, evolving to complete penile glans necrosis. CONCLUSIONS: With the
      increase of the number of patients on dialysis treatment, the prevalence of
      calciphylaxis will increase. A high index of suspicion is warranted in all
      patients with end-stage renal disease and who present the characteristic genital
      lesions. Treatment of this complication must include avoidance of all exogenous
      calcium, administration of calcitriol analogues to offset the PTH, emergency
      parathyroidectomy in the case of overt hyperparathyroidism and aggressive
      surgical treatment with total or partial penectomy.

PMID- 17511908
TI  - [Type I spinal atrophy (Werdnig-Hoffman disease). Case report].
AB  - BACKGROUND: We report a case of type I spinal muscular atrophy (SMA), also known
      as Werdnig-Hoffmann disease. METHODS: This was a descriptive case report. The
      patient was in the pediatric intensive care unit of a medical center. CASE
      REPORT: The patient was a 5 1/2 month-old male admitted to the emergency room
      from another hospital with a diagnosis of pneumonia with right apical atelectasis
      and with poor clinical evolution. The patient showed symptoms of acute
      respiratory failure and also generalized muscular weakness. Auscultation showed
      disseminated crackles, ronchi and hypotonic limbs. In view of his respiratory
      condition he was admitted to the Pediatric Intensive Care Unit and intubated.
      Chest X-ray showed a narrow chest with an apical infiltration and a left
      parahilar atelectasis. During the first days in the ICU, successful extubation
      was not possible because the patient showed hypoxemia and bradycardia. SMA was
      suspected because of the general muscular weakness; therefore, biopsy and
      neurophysiology studies were performed, demonstrating an axonal motor
      polyneuropathy with tongue fasciculations and signs of chronic denervation. The
      Pathology Service reported neurogenic fascicular atrophy and genetic analysis
      supported the diagnosis by blood test sampling, revealing a homozygous state for
      a deletion on exon 7 of the gene SMN1. Fifteen days after his admission to the
      hospital, the patient showed severe respiratory and heart failure to the CPR
      maneuvers. CONCLUSIONS: Type 1 SMA is a rare entity with few cases reported in
      the literature, but it is important for the pediatrician to be familiar with this
      disease because of its severe implications.

PMID- 17511909
TI  - [Chronic thromboembolic pulmonary hypertension].
AB  - Chronic thromboembolic pulmonary hypertension occurs in very few patients who
      have had history of a previous acute thromboembolic episode. However, its
      incidence has increased in recent years, actually not being so rare at all.
      Advances have been made in the pathophysiology, diagnostic approach and
      therapeutic alternatives as well what can be offered to those patients who are
      not suitable candidates for pulmonary thromboendarterectomy, which is definitive,
      curative and the treatment of choice in this subtype of pulmonary arterial
      hypertension. This review focuses on the diagnostic approach and novel
      pharmacological therapies in patients who are not candidates for surgery.

PMID- 17511910
TI  - [Pulmonary thromboendarterectomy in patients with chronic thromboembolic
      pulmonary hypertension].
AB  - Pulmonary arterial hypertension (PAH) secondary to chronic thromboembolic
      obstruction is a severe and potentially fatal condition. At the same time, PAH
      represents a real diagnostic challenge. This is a lethal disease in which the
      natural progression in the majority of cases may not be modified by medical
      therapy. It may be the only etiology radically cured by a complex surgical
      procedure being performed successfully at ten medical centers worldwide: the
      pulmonary thromboendarterectomy. More than three decades after the first
      successful thromboendarterectomy, improvements in technique in medical centers
      such as the University of California San Diego, in addition to the achieved
      advances in cerebral and myocardial protection on the past decades, guarantees at
      present a low morbimortality rate, offering excellent long-term results,
      improving quality of life and survival of patients. This review is mainly focused
      on the historical perspective of pulmonary thromboendarterectomy, indications,
      patient selection, surgical approach and improvements and outcomes obtained at
      the most experienced centers worldwide.

PMID- 17511911
TI  - [Mexican surgery in gynecology and obstetrics during the 19th century].
AB  - We present a historical framework for the initiation and development of
      obstetrical-gynecological (OB-Gyn) surgery during the 19th century in Mexico. The
      importance of a new vision is underlined, and the founders of medical science,
      the Romanticist surgeons who initiated the teaching of modern medicine and
      surgery, supported the change. The French influenced the advent of anesthesia,
      asepsis, antisepsis and transfusion, which has a major significance for the
      accomplishment of OB-Gyn Surgery. Important persons in this field of medicine are
      mentioned and we conclude with techniques of contemporary surgery in the next
      century, integrated with medical care.

PMID- 17511912
TI  - [Re: To invest in the health of our children is to invest in the future of
      Mexico].

PMID- 17511913
TI  - Colitis-associated cancer and dysplasia surveillance: an opposing perspective.

PMID- 17511914
TI  - Treatment of eosinophilic esophagitis: drugs, diet, or dilation?
AB  - A number of recent studies have demonstrated that a variety of treatments
      effectively improve symptoms and histology in the majority of patients with
      eosinophilic esophagitis. Therapeutic options include pharmacologic treatments,
      such as oral and topical corticosteroids and leukotriene-receptor antagonists. In
      children, the high response rates to dietary modification and elimination suggest
      that certain foods may serve as environmental triggers for the eosinophilic
      infiltration. Because many adults present with strictures, endoscopic esophageal
      dilation is another management modality. Despite these treatment options, several
      controversies exist in the recommended treatment strategy. Whether the goal of
      therapy is resolution of symptoms, tissue eosinophilia, or both remains uncertain
      owing to the paucity of data on the natural history of the condition.
      Furthermore, important differences in the clinical presentations of eosinophilic
      esophagitis in children and adults point toward the possible need for different
      treatment approaches in the two patient populations.

PMID- 17511915
TI  - Risk for cancer in Barrett's esophagus: medical versus surgical therapy.
AB  - Esophageal adenocarcinoma associated with Barrett's esophagus has been increasing
      in incidence over the past three decades. Our understanding of the risks for the
      development of esophageal adenocarcinoma in Barrett's esophagus is evolving.
      Newer treatment options for Barrett's esophagus are being developed in all areas,
      including endoscopic therapy, surgery, and chemoprevention trials.

PMID- 17511916
TI  - Extra-esophageal GERD: clinical dilemma of epidemiology versus clinical practice.
AB  - Gastroesophageal reflux disease (GERD) is a common disorder. A significant
      percentage of patients with GERD may experience extra-esophageal manifestations,
      such as asthma, cough, and laryngitis. Epidemiologic studies consistently
      demonstrate strong associations between GERD and potential extra-esophageal
      manifestations. However, randomized controlled studies evaluating the use of
      proton-pump inhibitors for treatment of extra-esophageal GERD have inconsistent
      results. In asthma, few randomized controlled studies have shown improvement in
      objective measures, such as forced expiratory volume or peak flow. For chronic
      cough, studies are all small and have not demonstrated consistent improvement
      with acid suppression. Even a recent well-designed large randomized controlled
      study in laryngitis demonstrated no difference in resolution of symptoms with
      acid suppression. Given the examples from the literature, the current treatment
      of extra-esophageal symptoms with acid suppression is controversial. Although
      improvement in symptoms has been shown in case series, it has not been consistent
      in randomized controlled studies. We offer potential explanations for the
      discrepancy between the epidemiologic associations and the lack of response to
      therapy in clinical trials.

PMID- 17511917
TI  - Polymeric diet alone versus corticosteroids in the treatment of active pediatric
      Crohn's disease.

PMID- 17511918
TI  - Advances and new technologies in adult endoscopy: can they be adapted to
      pediatrics?
AB  - Gastrointestinal endoscopy has revolutionized the management of many
      gastrointestinal and pancreatobiliary diseases and is now an integral part of the
      evaluation and treatment of gastrointestinal diseases in children and
      adolescents. Over the past several years, many new technological and therapeutic
      advances have been made in the field. These new technologies and therapies are
      often initially applied to adult patients and gradually adapted to children. This
      review focuses on recent advances and new technologies in adult endoscopy and
      discusses their adaptability to pediatric patients and the limitations to their
      adaptation.

PMID- 17511919
TI  - Novel and alternative therapies for childhood constipation.
AB  - Constipation is a worldwide problem that affects many children. Treatment of
      constipation is largely based on clinical experience rather than on evidence
      based controlled clinical trials. Stool softeners and cathartic agents in
      combination with behavioral interventions constitute the programs most commonly
      used to facilitate painless and frequent defecation. Long-term treatment is
      needed for most patients, and approximately 30% of children beyond puberty
      continue to struggle with symptoms of constipation, such as infrequent, painful
      evacuation of stools and fecal incontinence. Not surprisingly, chronicity of
      these bowel complaints may cause significant interference with the child's
      emotional growth and development. Development of new therapeutic strategies is
      necessary in order to treat these challenging patients more effectively. This
      review provides an overview of novel and alternative therapies, such as new
      drugs, surgery, and probiotics, that are being proposed for the treatment of
      childhood chronic constipation.

PMID- 17511920
TI  - Infant apnea and gastroesophageal reflux: a critical review and framework for
      further investigation.
AB  - Gastroesophageal reflux and apnea of prematurity are both common occurrences in
      premature infants. However, a causal relationship between the two remains
      controversial. Strong physiologic evidence indicates that a variety of protective
      reflex responses may elicit laryngeal adduction and apnea. Although a potential
      link between gastroesophageal reflux and apnea may exist through this pathway,
      clinical studies can be cited to either support or refute such a link in
      premature infants. The majority of gastroesophageal reflux episodes do not appear
      to be related to apnea. In a specific subset of events, a causal relationship may
      exist. Whether this is related to the character of the reflux episode or to a
      predisposition in a subpopulation of infants is unclear. This review presents the
      evidence for and against an association between gastroesophageal reflux and
      apnea, discusses techniques used in their evaluation, and identifies approaches
      for future investigation.

PMID- 17511921
TI  - The use of magnetic resonance cholangiopancreatography in children.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive method to
      evaluate a wide variety of pancreatobiliary disorders. These disorders include
      choledochal cyst, cholelithiasis, choledocholithiasis, biliary atresia, Caroli's
      disease, primary sclerosing cholangitis, disorders of the pancreatobiliary
      junction, pancreas divisum, and pancreatic duct abnormalities related to chronic
      pancreatitis. The use of MRCP in children is increasing as experience with MRCP
      grows, and its technological accuracy rivals that of endoscopic evaluation. We
      review the current state of MRCP use in children.

PMID- 17511922
TI  - Beyond five years: long-term follow-up in pediatric liver transplantation.
AB  - Pediatric liver transplant patients are now routinely surviving 10 years or more.
      Beyond the first year after transplant, surgical biliary or vascular
      complications are rare, and the incidence of acute rejection episodes falls
      precipitously. Attention is turning to minimizing the toxicity of
      immunosuppressive regimens and their potential negative impact on growth, bone
      health, cognitive development, renal function, and quality of life. Innovative
      combinations of immunosuppressive medications are being used as initial
      management after transplantation to minimize acute rejection and allow rapid
      weaning of corticosteroids and reduction in maintenance levels of calcineurin
      inhibitors. The substitution of potentially less toxic immunosuppressive agents,
      such as mycophenolate mofetil and rapamycin, is being studied in patients who
      develop renal dysfunction. A major current emphasis is on defining the natural
      history of long-term graft injury and elucidating histopathologic changes that
      mimic autoimmune chronic active hepatitis but are likely a form of chronic
      rejection due to production by the recipient of antibodies to foreign graft
      antigens. As patients survive longer, we are seeing various forms of immune
      dysregulation engendered by the presence of the graft and chronic
      immunosuppression of the host. By defining the resulting patterns of graft injury
      and understanding their immunopathogenesis, we can devise rational adjustments in
      immunosuppression that will preserve graft function and maximize graft life.

PMID- 17511923
TI  - Pediatric adenomatous polyposis syndromes: an update.
AB  - Juvenile polyps are a common finding in the pediatric population. In contrast,
      colon adenomas, which are viewed as dysplastic precancerous lesions, are found
      sporadically in late adulthood. Adenomas in children and young adults are highly
      unusual and suggest one of several forms of inherited colorectal cancer. These
      disorders show a predilection to early adenoma formation and can present in
      childhood. Familial adenomatous polyposis and Lynch syndrome are autosomal
      dominant, often with involvement of multiple family members, or can be seen in an
      individual arising from a de novo mutation. The most recently described
      adenomatous polyposis syndrome, MutYH-associated polyposis, is autosomal
      recessive, requiring an inherited mutation from each parent. All three
      adenomatous polyposis disorders can display tremendous variation in expression,
      even within the same family, and can have a common overlapping phenotype. These
      disorders require regular medical care to minimize cancer risk in the digestive
      tract and in other organ systems.

PMID- 17511924
TI  - Symptomatology, pathophysiology, diagnostic work-up, and treatment of
      Hirschsprung disease in infancy and childhood.
AB  - In the majority of infants and children with constipation, no obvious cause can
      be identified. A rare cause of constipation is Hirschsprung disease (HD). HD is
      characterized by the absence of ganglion cells from the anorectum for a variable
      length up to the duodenum. The extent of the aganglionic segment varies, but in
      most patients the lesion does not extend beyond the rectum and sigmoid colon.
      This review focuses on the passage of meconium, the recognition of HD, and new
      insights in its pathophysiology and genetics. The authors also provide a summary
      of the diagnostic evaluation and treatment of HD in infancy and childhood.

PMID- 17511925
TI  - Open-label study of valacyclovir 1.5 g twice daily for the treatment of
      uncomplicated herpes zoster in immunocompetent patients 18 years of age or older.
AB  - BACKGROUND: Herpes zoster (shingles) is a common disease caused by a reactivation
      of the latent varicella-zoster virus (chickenpox), which resides in the dorsal
      root ganglia. Valacyclovir HCl, the L-valyl ester of acyclovir, is an antiviral
      drug that is used to accelerate the resolution of the herpes zoster rash and
      associated pain and reduce the duration of postherpetic neuralgia. OBJECTIVE: To
      demonstrate the safety and efficacy of oral valacyclovir 1.5 g twice daily (bid)
      for the treatment of uncomplicated herpes zoster in immunocompetent patients over
      18 years of age. The dosing schedule of bid versus three times daily is desirable
      for enhancing patient compliance and to subsequently reduce the incidence of
      viral resistance. METHODS: One treatment group of 125 patients was administered
      oral valacyclovir 1.5 g bid for 7 days. Administration of the first dose occurred
      within 72 hours after onset of rash. Patients were seen and assessed for
      cutaneous healing, zoster-associated pain (ZAP), and/or zoster-associated
      abnormal sensations (ZAAS). Patients under 50 years of age were followed for 4
      weeks and patients 50 years of age and older were followed for a total of 24
      weeks. Patients >or= 50 years were also asked to record a daily diary on pain and
      abnormal sensations throughout the 24-week study period. Responses to resource
      use and quality of life questions were also collected. Safety was monitored by
      means of routine hematologic and biochemical assessments and reporting of adverse
      experiences. RESULTS: Data from this study were compared with historical control
      groups both for three times daily antiviral therapy and for placebo. The results
      showed that twice-daily dosing was as safe and effective as three times daily
      dosing for the reduction of ZAP and ZAAS. Adverse-effect profiles were similar
      between the two different regimens, and both treatment groups showed better
      outcomes than the historical placebo group. Because it is standard of care to
      administer antivirals for the treatment of acute herpes zoster, a placebo
      controlled trial is not possible, necessitating the use of historical controls.
      CONCLUSION: Oral valacyclovir 1.5 g bid is safe and effective for the treatment
      of uncomplicated herpes zoster in immunocompetent patients over 18 years of age.
      Twice-daily dosing may help increase patient compliance and therefore increase
      the effectiveness of treatment of the acute herpes zoster rash and the prevention
      of ZAP.

PMID- 17511926
TI  - Biologic therapeutics in the treatment of psoriasis. Part 1: review.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disease principally mediated
      by activated T cells, which release proinflammatory cytokines with reactive
      epidermal changes in the skin, producing the characteristic lesions of psoriasis.
      New research into possible treatment options has been inspired by increased
      understanding of the pathophysiology of psoriasis and advances in immunology and
      molecular biology permitting the development of targeted, highly active biologic
      agents. OBJECTIVE: The aim of this article is to review the efficacy and safety
      of five biologic therapeutics in the treatment of moderate to severe psoriasis
      and to provide practical guidelines for integration of these agents in the
      management of psoriasis. METHODS: We searched MEDLINE (1966-2005) for articles
      containing the key words: alefacept, efalizumab, etanercept, infliximab, and
      adalimumab and searched recent conference abstracts. RESULTS: Emerging
      immunotherapeutic agents (fusion proteins, recombinant cytokines, fusion toxins,
      or antibodies) target T cells or cytokines responsible for plaque formation that
      is characteristic of psoriasis. Alefacept is the first biologic to be approved in
      both the United States and Canada. More recently, efalizumab and etanercept and
      infliximab have been approved in the United States and Canada for plaque-type
      psoriasis. Adalimumab is currently in phase III clinical trials. CONCLUSION:
      These novel biologics offer an intriguing and effective treatment option for
      patients with moderate to severe psoriasis.

PMID- 17511927
TI  - Position statement for isotretinoin.

PMID- 17511929
TI  - Justification for separate consideration of two broad categories of cancer
      patient use of complementary medicine.
AB  - A strong argument can be made in support of the concept that individual cancer
      patient use of complementary medicine can be divided into two broad categories.
      This article provides the rationale for this statement and the potential utility
      of this approach.

PMID- 17511928
TI  - In vivo antitumor activity of ZYD88, a Chinese herbal medicine, in animal models
      with S180 sarcoma and Ehrlich tumor.
AB  - Cancer is a leading cause of death in the world. The continuous development of
      effective and nontoxic therapeutic agents is a major task in the battle of
      cancer. We report the in vivo effects of a Chinese herbal medicine, ZYD88, on the
      inhibition of tumor growth in an S(180) xenograft animal model and the
      improvement of animal survival in the Ehrlich tumor model. Oral administration of
      ZYD88 in mice with the xenograft S(180) sarcoma significantly inhibited tumor
      growth in a dose-dependent manner. Moreover, ZYD88 given to the animals with
      Ehrlich ascitic tumors by gavage significantly prolonged the life span compared
      with that of animals treated with saline. In both animal models, the effects of
      ZYD88 were comparable to those of a standard chemotherapeutic agent,
      cyclophosphamide, although it had few side effects. These results clearly
      demonstrated the in vivo anticancer activity of ZYD88 in two different animal
      models and suggest that ZYD88 is a potential agent for the clinical management of
      cancer and warrants further preclinical and clinical investigations.

PMID- 17511930
TI  - Religious and spiritual practices and identification among individuals living
      with cancer and other chronic disease.
AB  - Religion and spirituality in the context of health care are poorly understood,
      particularly for individuals with chronic illness. Using data from the 2003
      Complementary and Alternative Medicine supplement to the 2001 California Health
      Interview Survey, we examined whether cancer survivors (n = 1,777) and
      individuals with other chronic illnesses (n = 4,784) were either more likely to
      identify themselves as religious and spiritual or more likely to use religious
      and spiritual practices for health purposes than individuals with no disease (n =
      2,342). We observed that cancer survivors and individuals with chronic illnesses
      were more likely than those with no disease to use religious and spiritual prayer
      and healing practices. Individuals with chronic diseases were not inherently more
      likely to identify themselves as religious than were healthy individuals and were
      only slightly more likely to identify themselves as spiritual. These findings
      indicate that individuals with cancer and other chronic illnesses may be using
      religious and spiritual practices as a way to cope with their illness. Future
      research should continue to examine whether and how religious and spiritual
      practices are used as complementary or alternative medicine, and health care
      professionals should ask their patients about such use.

PMID- 17511931
TI  - How to improve accrual to clinical trials of symptom control 2: design issues.
AB  - The major reason that clinical trials in integrative oncology fail is that
      inadequate numbers of patients are accrued. One important cause of inadequate
      accrual is eligibility criteria that are overly restrictive. Investigators should
      critically examine every single inclusion or exclusion criterion to determine
      whether possible benefits to the study clearly outweigh harms in terms of reduced
      accrual. Accrual will also be harmed if the burdens for participation--traveling
      to appointments, completing questionnaires--are excessive compared with the
      benefits for patients. In a traditional randomized trial, half of participants do
      not receive treatment, reducing the benefits expected by any patient. This can be
      offset by guaranteeing free treatment to patients in the control group after they
      have completed the study. Patient burden can be reduced by limiting the number of
      hospital visits and avoiding excessive numbers of questionnaires.

PMID- 17511933
TI  - Aloe vera (Aloe barbadensis, Aloe capensis).

PMID- 17511932
TI  - Integrative Oncology Practice Guidelines.

PMID- 17511934
TI  - Papulopustular drug eruption due to an epidermal growth factor receptor
      inhibitors, erlotinib and cetuximab.
AB  - Two patients receiving epidermal growth factor receptor inhibitors for cancer
      treatment developed papulopustular eruptions a few days after starting treatment.
      One patient is a 56-year-old man with metastatic lung cancer treated with
      erlotinib. Bacterial cultures of the nares and a pustule showed no growth. The
      eruption improved with a lowered dose of erlotinib and the application of topical
      clindamycin solution and triamcinolone cream. The other patient is a 53-year-old
      man with metastatic rectal cancer treated with cetuximab. Bacterial culture of a
      pustule grew Staphylococcus aureus, and a skin biopsy specimen showed a
      suppurative folliculitis. The eruption improved with a two-week course of oral
      antibiotics and the application of topical clindamycin solution and triamcinolone
      cream. A papulopustular eruption occurs in up to 90% of patients treated with
      epidermal growth factor receptor blocking agents and may correlate with a
      positive response to chemotherapy. Treatment options are based on anecdotal
      evidence and may include topical antibiotics, topical glucocorticoids, and oral
      antibiotics for secondary infection.

PMID- 17511935
TI  - Acroangiodermatitis.
AB  - A 26-year-old man with a history of chronic primary lymphedema of the left lower
      extremity presented with elephantiasis, confluent, violaceous, mascerated
      plaques, and ulcers on the dorsal aspects of the toes of the left foot.
      Histopathologic examination showed a proliferation of small blood vessels
      associated with extravasated erythrocytes and hemosiderin deposits consistent
      with the diagnosis of acroangiodermatitis. Treatment of the focal ulcers includes
      compression therapy, local wound care, and surgical elimination of the shunt if
      there is an associated arteriovenous malformation.

PMID- 17511937
TI  - Multiple cutaneous granular-cell tumors.
AB  - A 54-year-old woman presented with subcutaneous nodules and a prior diagnosis of
      multiple, cutaneous granular-cell tumors. The first case of granular cell tumor
      was reported in 1854. It remains a rare tumor, which is most commonly seen in
      women. One-half are usually located in the head and neck region, mostly on the
      tongue. Approximately one third are cutaneous and 25 percent of the cases occur
      as multiple lesions.

PMID- 17511936
TI  - Familial multiple angiolipomatosis.
AB  - An 80-year-old man presented with a 50-year history of asymptomatic, subcutaneous
      masses on the arms, trunk, and legs. His father and maternal grandmother had had
      similar lesions. Histopathologic examination showed a benign angiolipoma; the
      same diagnosis has been made on several previous biopsy specimens. This patient's
      history and physical examination support the diagnosis of familial
      angiolipomatosis, which is a benign, autosomal-dominant condition that may be
      regarded as a subtype of familial multiple lipomatosis (FML) or as a distinct
      entity. Management of this condition may include liposuction or surgery to reduce
      the tumor burden.

PMID- 17511938
TI  - Folliculotropic mycosis fungoides.
AB  - A 72-year-old man presented with a 4-year history of asymptomatic erythematous
      plaques on his face, neck, and scalp. He had no systemic symptoms or
      lymphadenopathy. Histopathologic examination of a skin biopsy specimen showed a
      dense, diffuse infiltrate of lymphocytes and plasma cells, with epidermotropism
      and folliculotropism. T-cell receptor (TCR) gene rearrangement analysis performed
      on skin biopsy specimen showed a monoclonal cell population. A diagnosis of
      folliculotropic mycosis fungoides (MF) was made. This clinicopathologic variant
      of MF is usually associated with ordinary patch-plaque lesions. The prognosis of
      folliculotropic MF is best estimated using the TNM staging criteria. Many
      clinicians feel that this variant of MF portends a worse prognosis; however,
      there are no studies to support this idea. Folliculotropic MF may be more
      resistant to superficial therapies because of the depth of the neoplastic T-cells
      in the follicle.

PMID- 17511939
TI  - Hepatitis C virus infection, type III cryoglobulinemia, and necrotizing
      vasculitis.
AB  - A 53-year-old man with chronic hepatitis-C virus infection presented with livedo
      reticularis, purpura, and leg ulcers. A skin biopsy specimen showed a necrotizing
      vasculitis. The skin biopsy specimen and serology confirmed the diagnosis of type
      III cryoglobulinemia. Bone marrow and peripheral blood showed proliferation of
      atypical CD5-positive B cells that included a monoclonal population. There is
      growing evidence that chronic hepatitis-C infection can result in immune
      dysregulation and expansion of autoimmune B cells that produce cryoglobulins.

PMID- 17511941
TI  - Primary cutaneous B-cell lymphoma (low-grade, non large cell).
AB  - A 43-year-old man presented with erythematous, indurated plaques on the scalp in
      the setting of a 16-year history of recurrent cutaneous tumors of the head and
      trunk. Clinical and histopathologic findings were consistent with a diagnosis of
      primary cutaneous B-cell lymphoma. Laboratory data and computed tomography
      imaging of the chest, abdomen, and pelvis failed to show an associated systemic
      lymphoma. Primary cutaneous B-cell lymphomas are a heterogenous group of
      lymphomas that primarily involve the skin but have variable clinical,
      histopathologic, and immunologic phenotypes. Successful treatment for most
      localized subtypes consists of surgical excision and radiation therapy.
      Rituximab, a chimeric monoclonal antibody that binds the B-cell-specific antigen
      CD20, has shown promise in treating a number of primary cutaneous B-cell
      lymphomas.

PMID- 17511940
TI  - Keratosis follicularis (Darier-White disease), with an unusual palmoplantar
      keratoderma.
AB  - A 38-year-old woman presented with widespread, hyperkeratotic papules and plaques
      that had been present since childhood. Her mother, brother, and son have similar
      lesions. A diagnosis of keratosis follicularis was made, which has been treated
      with isotretinoin. Palmoplantar lesions of keratosis follicularis have been
      described as discrete, punctate keratoses, hyperkeratotic papules, small pits, or
      keratin-filled depressions. This patient has an unusual palmoplantar keratoderma
      in association with keratosis follicularis. The lesions are elevated, discrete,
      filiform, hyperkeratotic spires, which coalesce into large, hyperkeratotic
      plaques on the palms and soles.

PMID- 17511942
TI  - Lepromatous leprosy.
AB  - A 51-year-old woman presented with a 2-month history of pruritic, erythematous
      papules and plaques on her arms that were treated as chronic urticaria.
      Histopathologic examination demonstrated acid-fast bacilli, and a diagnosis of
      lepromatous leprosy was made. Presentation and treatment of leprosy are reviewed.

PMID- 17511943
TI  - Brooke-Spiegler syndrome.
AB  - A 46-year-old woman with Brooke-Spiegler syndrome has multiple cutaneous adnexal
      neoplasms on her face and scalp. One of the lesions has concurrent features of
      cylindroma, trichoepithelioma, and spiradenoma in the same specimen. Etiology,
      clinical features, malignant transformation, and treatment modalities for Brooke
      Spiegler syndrome are reviewed.

PMID- 17511944
TI  - Familial linear scleroderma (en coup de sabre) responsive to antimalarials and
      narrowband ultraviolet B therapy.
AB  - A 32-year-old woman and her 35-year-old sister presented with plaques of
      scleroderma en coup de sabre. The younger sister's disease was more severe and
      preceded the older sister's by 10 years. This is the second reported case of
      familial en coup de sabre, and the first case of horizontal transmission.
      Treatment of the younger sister with antimalarials and narrow-band ultraviolet B
      (NB-UVB) phototherapy slowed disease progression and reversed hair loss. The
      observation that NB-UVB was effective in this case of linear scleroderma suggests
      that it may be indicated as a therapy for cutaneous scleroderma.

PMID- 17511945
TI  - Lassueur-Graham-Little-Piccardi syndrome.
AB  - A 52-year-old man presented for evaluation of patchy alopecia of the scalp,
      axilla, and groin and of follicular spiny papules. Histopathologic examination
      showed a dense, follicular, lymphocytic infiltrate and interfollicular interface
      changes. Lassueur-Graham-Little-Piccardi syndrome is characterized by the triad
      of scarring, patchy alopecia of the scalp, non-cicatricial alopecia of the
      axillae and pubis, and a keratotic, follicular eruption. There may be an
      etiologic relationship with lichen planus. Treatment is difficult, although
      isolated reports have demonstrated success with cyclosporin and thalidomide.

PMID- 17511946
TI  - Lichen planus actinicus.
AB  - A 53-year-old woman presented for evaluation and treatment of discrete,
      violaceous, annular plaques on the forehead and cheeks. The biopsy specimen and
      the clinical presentation were consistent with lichen planus actinicus. Lichen
      planus actinicus is a photosensitive variant of lichen planus that can present
      with annular, melasma-like, dyschromic, or violaceous plaques in sun-exposed
      areas. The clinical manifestations of lichen planus actinicus and treatments are
      discussed.

PMID- 17511947
TI  - Eruptive vellus hair cysts.
AB  - A 20-year-old man presented with multiple, asymptomatic, follicular papules that
      were distributed over his abdomen. Microscopic examination showed classic
      features of a vellus hair cyst. The term eruptive vellus hair cysts refers to a
      benign condition, which may be inherited or acquired. Apart from occasional
      pruritus, cosmetic disability is the chief concern of most patients. An estimated
      25 percent of lesions remit spontaneously; however, treatment of persistent
      lesions is often challenging with disappointing results.

PMID- 17511948
TI  - Epidermolysis bullosa acquisita.
AB  - A 29-year-old woman presented with 8 months of multiple vesicles, erosions, and
      milia on the dorsa of her hands and feet. Histopathologic examination
      demonstrated a subepidermal blister, with a paucity of eosinophils and a lack of
      blood vessel wall thickening or caterpillar bodies. A direct immunofluorescence
      test showed a linear deposit of IgG at the dermo-epidermal junction. These
      findings were consistent with a diagnosis of epidermolysis bullosa acquisita.
      This case is a classic example of this rare blistering disease, in which patients
      produce autoantibodies to collagen VII, which is the major component of the
      anchoring fibrils.

PMID- 17511949
TI  - Russell-Silver syndrome.
AB  - A 27-year-old woman presented with congenital growth retardation, facial
      dysmorphism, and limb asymmetry. Additional clinical findings lead to a diagnosis
      of Russell-Silver syndrome with sporadic occurrence. Treatment requires a
      multidisciplinary approach. Clinical features and treatment options are reviewed.

PMID- 17511950
TI  - Glomuvenous malformations.
AB  - A 9-year-old girl presented with a congenital, blue-purple, partially
      compressible plaque with a cobblestone surface on the left lateral foot and
      ankle. Similar, solitary, blue nodules later appeared elsewhere on the
      extremities. The lesions were tender to palpation and were associated with
      spontaneous paroxysms of pain and paresthesias. Histopathologic evaluation of a
      skin biopsy specimen showed rows of glomus cells that surrounded thin-walled
      vascular channels, which confirmed the diagnosis of glomuvenous malformations.
      This autosomal dominant condition, which is due to mutations in the GLMN gene,
      presents with clinical findings that are distinct from those of familial,
      multiple, cutaneous and mucosal venous malformations. Treatment options include
      excision, sclerotherapy, and laser therapy (ablative or pulsed dye).

PMID- 17511951
TI  - Mycosis fungoides with depigmentation secondary to treatment.
AB  - A 51-year-old man presented with itchy, erythematous patches and plaques on his
      trunk, arms, and legs. A skin biopsy specimen showed mycosis fungoides. Initially
      the patient did not respond to PUVA photochemotherapy but later improved on NB
      UVB phototherapy combined with bexarotene and interferon-alpha. The lesions
      progressed from erythematous patches and plaques to hyperpigmented patches with
      central depigmentation and localized areas of follicular repigmentation. The
      development of depigmentation after PUVA photochemotherapy for mycosis fungoides
      has been described in the literature and does not have associated prognostic
      implications. It is important to be cognizant of phototoxicity associated with
      PUVA photochemotherapy or NB-UVB phototherapy in patients with mycosis fungoides,
      who may be taking photosensitizing medications or have depigmented patches which
      renders them more sensitive to lower doses of ultraviolet light.

PMID- 17511952
TI  - Actinic granuloma.
AB  - A 45-year-old man presented with a 3-year history of asymptomatic, annular,
      erythematous plaques on the face and neck. Histopathologic examination showed
      sarcoidal granulomas with an associated mixed-cell infiltrate, loss of elastic
      fibers, and no increase in mucin. These findings were consistent with a diagnosis
      of actinic granuloma, which is an uncommon, idiopathic disease that is
      characterized by granuloma annulare-like plaques on sun-exposed areas.

PMID- 17511953
TI  - Psoriatic onycho-pachydermo periostitis.
AB  - A 46-year-old woman presented with onycholysis and swollen, painful digits. No
      other stigmata of psoriasis were present. Magnetic resonance imaging of the hands
      showed an extensive periosteal reaction of the phalangeal tuft. Psoriatic onycho
      pachydermo periostitis (POPP) is a rare subset of psoriatic arthritis that is
      characterized by psoriatic onychodystrophy, connective-tissue thickening above
      the distal phalanx, and a periosteal reaction. Treatment of POPP is difficult;
      however, low-dose methotrexate and anti-TNF-alpha agents may be beneficial. In
      patients who are unresponsive or intolerant of these medications, other biologic
      and non-biologic disease modifying anti-rheumatic drugs need to be considered.

PMID- 17511954
TI  - Pachyonychia congenita associated with median rhomboid glossitis.
AB  - A 3-year-old girl presented with subungual hyperkeratosis and nail plates with
      increased transverse curvature, distal elevation, yellow-brown discoloration, and
      mild thickening. The changes, which affected all 20 nails, had developed during
      the first year of life. Mucocutaneous examination showed the presence of median
      rhomboid glossitis. The patient's mother had similar nail changes, which had been
      present since infancy as well as a focal plantar keratoderma and hyperhidrosis.
      The patient's clinical presentation and history were compatible with a diagnosis
      of pachyonychia congenita, a rare heritable disease that affects the nails, skin,
      oral and laryngeal mucosae, teeth, and hair. Dominant-negative mutations in four
      keratin genes (K6a, K6b, K16, and K17) lead to keratinocyte fragility and the
      resultant pachyonychia congenita phenotype. Successful targeted therapies are
      currently lacking for this oftentimes disabling disorder. Although oral
      manifestations are a common feature of PC, to our knowledge, this represents the
      first report of median rhomboid glossitis in association with PC.

PMID- 17511955
TI  - Tuberous sclerosis.
AB  - A 46-year-old woman presented with multiple, skin-colored, hyperpigmented, dome
      shaped facial papules. Histopathologic examination was consistent with
      angiofibromas. Clinical history and examination were consistent with tuberous
      sclerosis. The clinical manifestations, pathogenesis, evaluation, and treatment
      of tuberous sclerosis are discussed.

PMID- 17511956
TI  - Lichen aureus.

PMID- 17511957
TI  - Antiplatelet therapy for atherothrombotic disease: an update for the primary care
      physician.
AB  - Atherothrombosis is a progressive and generalized pathologic process that affects
      the vascular system. Clinical manifestations of atherothrombosis depend on the
      affected vascular bed and include acute coronary syndromes, stroke, and
      peripheral arterial disease. Ischemia associated with atherothrombosis is highly
      prevalent, affecting millions of people each year. Many patients experience
      multiple ischemic events within the first year of an initial event. The mainstay
      for prevention includes risk factor management through lifestyle modification and
      treatment of underlying disease. Guidelines have been published for secondary
      prevention of atherothrombosis-related cardiovascular disease, including use of
      various long-term pharmacotherapies, such as antiplatelet agents, statins, and
      angiotensin-converting enzyme inhibitors. Implementation of effective treatment
      strategies requires an awareness of the guidelines by physicians to ensure that
      both acute therapy and long-term management are addressed. This review is based
      on treatment guidelines and selected peer-reviewed publications identified
      through a MEDLINE and PubMed literature search, primarily from January 1996 to
      December 2006, that relate to clinical trials of antiplatelet therapy in patients
      with atherothrombotic disease. Secondary prevention strategies for patients with
      atherothrombosis are discussed, highlighting current guideline recommendations
      and programs designed to encourage a continuum of care from the acute to the
      ambulatory setting.

PMID- 17511958
TI  - Spermine and spermidine inhibition of photosystem II: Disassembly of the oxygen
      evolving complex and consequent perturbation in electron donation from TyrZ to
      P680+ and the quinone acceptors QA- to QB.
AB  - Polyamines are implicated in plant growth and stress response. However, the
      polyamines spermine and spermidine were shown to elicit strong inhibitory effects
      in photosystem II (PSII) submembrane fractions. We have studied the mechanism of
      this inhibitory action in detail. The inhibition of electron transport in PSII
      submembrane fractions treated with millimolar concentrations of spermine or
      spermidine led to the decline of plastoquinone reduction, which was reversed by
      the artificial electron donor diphenylcarbazide. The above inhibition was due to
      the loss of the extrinsic polypeptides associated with the oxygen evolving
      complex. Thermoluminescence measurements revealed that charge recombination
      between the quinone acceptors of PSII, QA and QB, and the S2 state of the Mn
      cluster was abolished. Also, the dark decay of chlorophyll fluorescence after a
      single turn-over white flash was greatly retarded indicating a slower rate of QA-
      reoxidation.

PMID- 17511959
TI  - Temporal regulation of Stat5 activity in determination of cell differentiation
      program.
AB  - Although Stat5 is activated by various cytokines, only erythropoietin (Epo) and a
      small number of cytokines induce Stat5-dependent erythroid differentiation. Here,
      by using a reporter gene system to monitor transcriptional activity of Stat5, we
      showed that Epo but not interleukin (IL)-3 supports sustained activation of
      Stat5, which induces globin gene expression. IL-3 or IL-2 stimulation inhibits
      Epo-induced globin gene expression. The acidic region of the IL-2 receptor beta
      chain was essential for this inhibition. These results underscore the importance
      of temporal regulation of Stat activity for regulation of cytokine-specific cell
      differentiation.

PMID- 17511960
TI  - Profiling of adipokines secreted from human subcutaneous adipose tissue in
      response to PPAR agonists.
AB  - The role of PPARs in the regulation of human adipose tissue secretome has
      received little attention despite its potential importance in the therapeutic
      actions of PPAR agonists. Here, we have investigated the effect of selective
      PPARgamma, PPARalpha, and PPARbeta/delta agonists on the production of adipokines
      by human subcutaneous adipose tissue. Antibody arrays were used to measure
      secreted factors in media from cultured adipose tissue explants. Sixteen proteins
      were produced in significant amounts. Activation of PPARs regulated the
      production of five proteins. Treatments with the three PPAR agonists decreased
      the secretion of leptin and interleukin-6. PPARalpha and beta/delta agonists
      markedly enhanced hepatocyte growth factor secretion whereas PPARbeta/delta down
      regulated angiogenin and up-regulated TIMP-1 release. Hepatocyte growth factor,
      interleukin-6, and TIMP-1 are chiefly expressed in cells from the stromal
      vascular fraction whereas angiogenin is expressed in both adipocytes and cells
      from the stromal vascular fraction. Our data show that PPAR agonists modulate
      secretion of bioactive molecules from the different cell types composing human
      adipose tissue.

PMID- 17511961
TI  - Identifying and characterising the Plasmodium falciparum RhopH3 Plasmodium vivax
      homologue.
AB  - Four Plasmodium species cause malaria in humans, Plasmodium falciparum being the
      most widely studied to date. All Plasmodium species have paired club-shaped
      organelles towards their apical extreme named rhoptries that contain many lipids
      and proteins which are released during target cell invasion. P. falciparum RhopH3
      is a rhoptry protein triggering important immune responses in patients from
      endemic regions. It has also been shown that anti-RhopH3 antibodies inhibit in
      vitro invasion of erythrocytes. Recent immunisation studies in mice with the
      Plasmodium yoelii and Plasmodium berghei RhopH3 P. falciparum homologue proteins
      found that they are able to induce protection in murine models. This study
      described identifying and characterising RhopH3 protein in Plasmodium vivax; it
      is encoded by a seven exon gene and expressed during the parasite's asexual
      stage. PvRhopH3 has similar processing to its homologue in P. falciparum and
      presents a cellular immunolocalisation pattern characteristic of rhoptry
      proteins.

PMID- 17511962
TI  - Membrane microdomain formation is crucial in epiboly during gastrulation of
      medaka.
AB  - Membrane microdomain (microdomain) was isolated from early gastrula embryos. The
      isolated microdomain was characterized by enrichment of cholesterol and
      sphingomyelin, and by the presence of huge glycoproteins containing Lewis X
      structure. Importance of the microdomain in the progress of epiboly was assessed
      using methyl beta-cyclodextrin (MBCD) and C2-ceramide that disrupt microdomains
      through different mechanisms. Both reagents efficiently disrupted the microdomain
      structure and concomitantly impaired epiboly. Interestingly, when embryos
      pretreated with MBCD, a cholesterol-binding molecule, were exogenously
      supplemented with cholesterol, the embryos underwent not only reconstitution of
      the microdomain, but also complete restoration to the normal epiboly. Thus,
      normal or impaired development is reversibly controlled by the cholesterol
      dependent formation or disruption of microdomains. The most typical phenotype of
      the microdomain-disrupted embryos is detachment of cells from the blastoderm,
      suggesting that a major contribution of microdomains to epiboly is cell adhesion
      of blastodermal cells.

PMID- 17511963
TI  - CAPN10 mRNA splicing and decay is not affected by a SNP associated with
      susceptibility to type 2 diabetes.
AB  - The mRNA concentration of CAPN10, a T2D susceptibility gene was measured in white
      blood cells of T2D and healthy subjects, as well as the transcript half-life in
      two SNP-43 genotyped human cell lines, to evaluate a possible relationship
      between this SNP-43 and the transcript half-life. T2D patients with the SNP-43 G
      allele had 4.6-fold more CAPN10 transcripts compared to subjects with the A
      allele. The mRNA half-life of this transcript in 293T cells (SNP-43 G/G) and
      Jurkat cells (SNP-43 A/A) was of 8h. We provide evidence that in T2D subjects the
      G-allele increases the CAPN10 mRNA levels. We propose a defective CAPN10 pre-mRNA
      processing is responsible for the decreased levels of SNP-43 A-allele transcripts
      in peripheral white cells of healthy and T2D individuals.

PMID- 17511964
TI  - Identification of proteins expressed at extremely low level in Arabidopsis
      leaves.
AB  - 2-DE related techniques have been broadly used for protein separation and
      identification in recent years. However, many important cellular components often
      escape detection by 2-DE due to its inherent low resolution. Here we use a polyU
      affinity column to enrich proteins with nucleotide-binding motifs. As a result,
      26 enriched protein spots, including three new Arabidopsis RNA-binding proteins
      cp31A, cp31B, and CSP41, are identified by MALDI-TOF-MS. In the sum, 15 protein
      spots encoded by 12 individual genes are observed on the 2-DE only after binding
      to the polyU-affinity column. Two of these genes are expressed at lower than 0.1%
      the level of TUB4 that were considered mainly as non-expressed genes in several
      ATH1 microarray analysis of Arabidopsis leaf samples. Our results suggest that
      polyU or similar media may be combined with 2-DE techniques to identify cellular
      proteins with extremely low transcription levels to fulfill specific research
      needs.

PMID- 17511965
TI  - The C-terminal domain of the nuclear factor I-B2 isoform is glycosylated and
      transactivates the WAP gene in the JEG-3 cells.
AB  - The transcription factor nuclear factor I (NFI) has been shown previously both in
      vivo and in vitro to be involved in the cooperative regulation of whey acidic
      protein (WAP) gene transcription along with the glucocorticoid receptor and
      STAT5. In addition, one of the specific NFI isoforms, NFI-B2, was demonstrated in
      transient co-transfection experiments in JEG cells, which lack endogenous NFI, to
      be preferentially involved in the cooperative regulation of WAP gene expression.
      A comparison of the DNA-binding specificities of the different NFI isoforms only
      partially explained their differential ability to activate the WAP gene
      transcription. Here, we analyzed the transactivation regions of two NFI isoforms
      by making chimeric proteins between the NFI-A and B isoforms. Though, their DNA
      binding specificities were not altered as compared to the corresponding wild-type
      transcription factors, the C-terminal region of the NFI-B isoform was shown to
      preferentially activate WAP gene transcription in cooperation with GR and STAT5
      in transient co-transfection assays in JEG-3 cells. Furthermore, determination of
      serine and threonine-specific glycosylation (O-linked N-acetylglucosamine) of the
      C-terminus of the NFI-B isoform suggested that the secondary modification by O
      GlcNAc might play a role in the cooperative regulation of WAP gene transcription
      by NFI-B2 and STAT5.

PMID- 17511966
TI  - Structural role of the secondary active domain of HIV-2 NCp8 in multi
      functionality.
AB  - Nucleocapsid protein of HIV, containing two CCHC-type zinc fingers connected by a
      linker, is a multi-functional protein involved in many critical steps of the HIV
      life cycle. Several in vitro investigations demonstrated that the reactivities of
      the first zinc finger flanked by the linker of HIV-1 NCp7 and HIV-2 NCp8 were
      essential for binding to viral RNA, however, that of the second zinc finger
      flanked by the linker of NCp7 was very weak and non-specific, whereas the part of
      NCp8 called NCp8-f2, interacted strongly and specifically with viral RNA. In this
      study, the three-dimensional structure of NCp8-f2 was determined for the first
      time. Furthermore, we established that NCp8-f2 specifically binds to the stem
      loop SD in viral RNA, and that the hydrophobic cleft and the basic residues close
      to the cleft were essential for specific binding to SD. We discuss the functional
      significance of NCp8-f2 for NCp8 being a multi-functional protein.

PMID- 17511967
TI  - Event-related functional magnetic resonance imaging of response inhibition in
      obsessive-compulsive disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) has been hypothesized to involve
      inhibitory control dysfunction related to abnormal frontal-striatal-thalamic
      cortical (FSTC) circuitry. METHODS: We examined the neural substrates of response
      inhibition in adults with OCD using functional magnetic resonance imaging (fMRI)
      and a go/no-go task. Participants consisted of 12 adults with OCD and 14 healthy
      comparison subjects. RESULTS: During response inhibition, healthy adults showed
      predominantly right-hemisphere activation including the right inferior frontal
      gyrus, whereas the patient group showed a more diffuse, bilateral pattern of
      activation. Furthermore, the OCD group demonstrated less activation than the
      comparison group in several right-hemisphere regions during response inhibition,
      including inferior and medial frontal gyri. Symptom severity was inversely
      correlated with activation in right orbitofrontal and anterior cingulate gyri and
      positively correlated with thalamic and posterior cortical activations. Neither
      depressed mood nor medication status could account for the results. CONCLUSIONS:
      These findings indicate that adults with OCD demonstrate underactivation of FSTC
      circuitry during response inhibition. Results suggest that the thalamus and
      related circuitry may play a role in the expression or intensity of OCD symptoms,
      whereas right frontal subregions may be involved in the suppression of symptoms.

PMID- 17511968
TI  - Positive allosteric modulation of metabotropic glutamate 5 (mGlu5) receptors
      reverses N-Methyl-D-aspartate antagonist-induced alteration of neuronal firing in
      prefrontal cortex.
AB  - BACKGROUND: Several lines of evidence suggest that N-methyl-D-aspartate (NMDA)
      receptor hypofunction may be associated with schizophrenia. Activation of
      metabotropic glutamate 5 (mGlu5) receptors enhances NMDA receptor mediated
      currents in vitro, implying that allosteric modulation of mGlu5 receptors may
      have therapeutic efficacy for schizophrenia. The aim of this study was to
      determine if positive allosteric modulators of mGlu5 receptors are effective in
      reversing two cellular effects of NMDA receptor antagonists that are relevant to
      schizophrenia: increases in corticolimbic dopamine neurotransmission and
      disruption of neuronal activity in the prefrontal cortex (PFC). METHODS: In
      freely moving rats, we measured the effects of the positive modulator of mGlu5
      receptor 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) alone or in
      combination with the NMDA antagonist MK801 on 1) spontaneous firing and bursting
      of medial PFC (mPFC) neurons, and 2) dopamine release as measured by
      microdialysis in the mPFC and nucleus accumbens (NAc). RESULTS: The predominant
      effect of CDPPB on mPFC neurons was excitatory, leading to an overall excitatory
      population response. Pretreatment with CDPPB prevented MK801-induced excessive
      firing and reduced spontaneous bursting. In contrast, CDPPB had no significant
      effect on basal dopamine release as compared with control rats and did not alter
      MK801-induced activation of dopamine release in the mPFC and NAc. CONCLUSIONS:
      These results show that positive modulation of mGlu5 receptors reverses the
      effects of noncompetitive NMDA antagonists on cortical neuronal firing without
      affecting dopamine neurotransmission. Thus, these compounds may be effective in
      ameliorating PFC mediated behavioral abnormalities that results from NMDA
      receptor hypofunction.

PMID- 17511969
TI  - Electrophysiologic changes in ventral midbrain dopaminergic neurons resulting
      from (+/-) -3,4-methylenedioxymethamphetamine (MDMA-"Ecstasy").
AB  - BACKGROUND: Although dopamine (DA) has been implicated in the psychostimulant
      properties of 3,4-methylenedioxymethamphetamine (MDMA), there is no detailed
      information on its modalities of action on single ventral midbrain dopaminergic
      neurons. METHODS: We examined the actions of MDMA on intracellularly recorded
      dopaminergic neurons maintained in slices. RESULTS: At 1 micromol/L, MDMA
      depolarized and excited the cells; at 3 micromol/L, either excited or inhibited
      the neurons. Interestingly, higher concentrations (10-30 micromol/L) inhibited
      firing through membrane hyperpolarization or caused an outward current. Whereas
      MDMA's excitatory effects were antagonized by pindolol, indicating involvement of
      5-HT 1B receptors, the inhibitory effects were counteracted by sulpiride
      indicating involvement D2 receptors. Treatment of the cells with carbidopa
      eliminated MDMA-induced firing inhibition and membrane hyperpolarization. MDMA
      enhanced DA-induced cellular responses but reduced those of amphetamine. Cocaine
      induced outward currents were not affected by MDMA. These actions are consistent
      with inhibition of the DA transporter. Moreover, MDMA depressed the GABA(B) IPSP
      by activating 5-HT 1B receptors. CONCLUSIONS: Our data demonstrate that 3-30
      micromol/L MDMA preferentially inhibits the dopaminergic cells via indirect
      activation of D2 autoreceptors due to increased extracellular concentration of
      DA. In contrast, reduction of the GABA(B) IPSP could partially account for
      excitation caused by 1-3 micromol/L drug.

PMID- 17511970
TI  - Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597
      in a rat model of chronic mild stress.
AB  - BACKGROUND: The endocannabinoid anandamide may be involved in the regulation of
      emotional reactivity. In particular, it has been shown that pharmacological
      inhibition of the enzyme fatty acid amide hydrolase (FAAH), which catalyzes the
      intracellular hydrolysis of anandamide, elicits anxiolytic-like and
      antidepressant-like effects in rodents. METHODS: We investigated the impact of
      chronic treatment with the selective FAAH inhibitor, URB597 (also termed KDS
      4103), on the outcomes of the chronic mild stress (CMS) in rats, a behavioral
      model with high isomorphism to human depression. RESULTS: Daily administration of
      URB597 (.3 mg kg(-1), intraperitoneal [IP]) for 5 weeks corrected the reduction
      in body weight gain and sucrose intake induced by CMS. The antidepressant
      imipramine (20 mg kg(-1), once daily, IP) produced a similar response, whereas
      lower doses of URB597 were either marginally effective (.1 mg kg(-1)) or
      ineffective (.03 mg kg(-1)). Treatment with URB597 (.3 mg kg(-1)) resulted in a
      profound inhibition of brain FAAH activity in both CMS-exposed and control rats.
      Furthermore, the drug regimen increased anandamide levels in midbrain, striatum,
      and thalamus. CONCLUSIONS: URB597 exerts antidepressant-like effects in a highly
      specific and predictive animal model of depression. These effects may depend on
      the ability of URB597 to enhance anandamide signaling in select regions of the
      brain.

PMID- 17511971
TI  - Amygdala volume analysis in female twins with major depression.
AB  - BACKGROUND: Previous research examining the amygdala volumes in major depressive
      disorder (MDD) has found conflicting evidence for association. Furthermore, few
      of these studies have examined differences in individuals with an onset during
      childhood or adolescence. This study examined amygdala volume and its potential
      association with early onset major depression. METHODS: A community-based sample
      of 47 right-handed young adult female monozygotic and dizygotic twin pairs was
      examined. For 29 twin pairs, one twin per pair had a lifetime history of MDD,
      while 18 age-matched control twin pairs had no lifetime history of MDD or other
      Axis I disorder. Core, noncore, and total amygdala volumes were estimated based
      on a combination of manual tracing, automated segmentation, and expert rater
      regional boundary definitions. RESULTS: No significant differences were found in
      amygdala volumes between depressed, high-risk, or control subjects. However,
      analyses comparing control monozygotic twins to randomly created control subject
      pairs suggest that there are familial, perhaps genetic, influences on core and
      total amygdala volumes. CONCLUSIONS: Findings suggest that although there were no
      significant differences in amygdala volumes between groups, familial factors
      influence amygdala volumes. Discrepancies between studies measuring amygdala
      volume in MDD may be due to differences in amygdala boundary definitions.

PMID- 17511972
TI  - Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET
      imaging study using altropane.
AB  - BACKGROUND: The dopamine transporter (DAT) is known to be a key regulator of
      dopamine, and recent studies of genetics, treatment, and imaging have highlighted
      the role of DAT in attention-deficit/hyperactivity disorder (ADHD). The findings
      of in vivo neuroimaging of DAT in ADHD have been somewhat discrepant, however.
      METHOD: Dopamine transporter binding was measured using a highly selective ligand
      (C-11 altropane) and positron emission tomography (PET). The sample consisted of
      47 well-characterized, treatment-naive, nonsmoking, non-comorbid adults with and
      without ADHD. Additionally, control subjects had few symptoms of ADHD. RESULTS:
      Results showed significantly increased DAT binding in the right caudate in adults
      with ADHD compared with matched control subjects without this disorder.
      CONCLUSIONS: These results confirm abnormal DAT binding in the striatum of adults
      with ADHD and provide further support that dysregulation of DAT may be an
      important component of the pathophysiology of ADHD.

PMID- 17511974
TI  - Synthesis and NMR experiments of (4,5,6-13C)-deoxymannojirimycin. A new entry to
      13C-labeled glycosidase inhibitors.
AB  - The synthesis of (4,5,6-13C)-deoxymannojirimycin is described. The route employed
      is based on Sharpless asymmetric epoxidation of (1,2,3-13C)(E)-2,4-pentadien-1-ol
      and uses ring-closing metathesis as a key step. The labeled compound may be
      easily used for protein-binding experiments using NMR spectroscopic methods.

PMID- 17511973
TI  - Effects of immobilization stress on neurochemical markers in the motivational
      system of the male rat.
AB  - Mesolimbic regions involved in motivated behavior are altered in animals
      undergoing repeated exposure to social stress. Here we test the hypothesis that
      other forms of persistent stress would also influence these same endpoints. Adult
      male Sprague-Dawley rats were exposed to immobilization stress either once (2 h)
      or repeatedly (2 hx10 days) and brains were harvested immediately after the last
      immobilization. A trio of indirect markers associated with dopaminergic activity
      was measured including dopamine transporter (DAT) and dopamine D2 receptor
      subtype (D2r) ligand levels as well as mRNA levels of the endogenous opioid
      enkephalin (ENK-mRNA). A single 2-h session of immobilization stress produced an
      increase in striatal ENK-mRNA levels and DAT ligand binding compared with group
      housed controls. In animals undergoing repeated immobilization stress and singly
      housed post-stress, we found a significant reversal in the direction of ENK-mRNA
      levels and DAT binding in the striatum, in addition to an increase in D2r-binding
      density in the shell of the nucleus accumbens compared with single-stress-exposed
      rats. In another experiment using the same stress paradigm but allowing pair
      housing post-stress, we found no alteration of ENK-mRNA but significant increases
      in DAT and D2r binding in the dorsal striatum. A major difference between single
      and group housing is the habituation of the corticosterone (CORT) stress response
      over 10-day stress in group-housed rats. The present results parallel previous
      findings by our laboratory that repeated stress results in a relative reduction
      of ENK-mRNA levels and increased D2r-binding density in the striatum of rats.
      Furthermore, our data are consistent with the hypothesis that chronic stress
      induces an allostatic attenuation of the mesolimbic dopaminergic system in
      animals that do not habituate to the stressor, possibly due in part to persistent
      CORT elevations.

PMID- 17511975
TI  - The conformational behaviour of the C-glycosyl analogue of sulfatide studied by
      NMR in SDS micelles.
AB  - The conformational behaviour of sulfatide and its C-glycosyl analogue has been
      studied by using a combination of J and NOE data assisted by molecular mechanics
      calculations. There is a major exoanomeric conformation around the phi angle of
      both molecules with two or three conformers contributing to the equilibrium
      around psi. The MM3* calculations only provide a qualitative description of the
      actual population distribution. Despite this geometrical similarity, the
      quantitative analysis of the NOE intensities at a variety of mixing times
      indicates that the motion around the pseudoglycosidic linkages of the C-glycosyl
      analogue is faster than that for the natural compound.

PMID- 17511976
TI  - The glass transition temperatures of amorphous trehalose-water mixtures and the
      mobility of water: an experimental and in silico study.
AB  - Isothermal-isobaric molecular dynamics simulations are used to calculate the
      specific volume of models of trehalose and three amorphous trehalose-water
      mixtures (2.9%, 4.5% and 5.3% (w/w) water, respectively) as a function of
      temperature. Plots of specific volume versus temperature exhibit a characteristic
      change in slope when the amorphous systems change from the glassy to the rubbery
      state and the intersection of the two regression lines provides an estimate of
      the glass transition temperature T(g). A comparison of the calculated and
      experimental T(g) values, as obtained from differential scanning calorimetry,
      shows that despite the predicted values being systematically higher (about 21
      26K), the trend and the incremental differences between the T(g) values have been
      computed correctly:
      T(g)(5.3%(w/w))<T(g)(4.5%(w/w))<T(g)(2.9%(w/w))<T(g)(0.0%(w/w)). The mobility of
      water has been investigated over temperature ranges covering the rubbery and the
      glassy phases of the trehalose-water mixtures by calculating the diffusion
      coefficients of water. The temperature dependence of the diffusion coefficient
      changes in the region of the glass transition and can be used as well to estimate
      T(g) values. The activation energies for water diffusion were found to be
      independent of the amount of water in amorphous trehalose.

PMID- 17511977
TI  - C-reactive protein gene polymorphism 1009A>G is associated with serum CRP levels
      in Chinese men: a TCVGHAGE study.
AB  - BACKGROUND: Increased concentrations of high-sensitivity CRP (hs-CRP) are
      associated with increased risk of cardiovascular disease. This increase might be
      caused by low-grade inflammation, but a number of studies have suggested that
      serum CRP concentrations are under genetic control. Since the relation between
      CRP concentration and cardiovascular diseases occurs across ethnicities, we
      determined whether CRP gene variants affect fasting hs-CRP concentrations in a
      cohort of Chinese men. METHODS: High-sensitivity CRP concentrations were measured
      in 369 Chinese men. Six polymorphisms were identified by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) and direct
      sequencing within the CRP gene: 969T>C, 1009A>G, and a 3-allele polymorphism
      1440C>A>T in the 5' UTR (promoter region), 2667G>C in exon 2, and 3872A>G and
      5992T>A in the 3' UTR. RESULTS: In a group of participants (n=328) whose fasting
      serum hs-CRP concentrations were within the 5th to 95th percentile, we found that
      the genetic polymorphism 1009A>G was significantly associated with fasting serum
      hs-CRP concentrations (GG vs. AG or AA genotypes, CRP concentrations 0.072+/
      0.062 vs. 0.176+/-0.166 and 0.166+/-0.185 mg/dl, mean+/-S.D., both P=0.023).
      Furthermore, subjects carrying the 1009G bearing haplotype exhibited the lowest
      CRP concentrations (P=0.05). CONCLUSION: The CRP 1009A>G genotypes and associated
      haplotypes were associated with lower fasting serum hs-CRP concentrations in a
      group of elderly Chinese men.

PMID- 17511978
TI  - The robustness of the Roche 2nd generation homogenous HDL cholesterol (PEGME)
      method: assessment of the effect of serum sample storage for up to 8 years at -80
      degrees C.
AB  - BACKGROUND: Low HDL-cholesterol (HDL-C) is a strong and independent
      cardiovascular risk factor. Clinical trials often necessitate storage of samples
      before assay. Results are lacking for longer-term storage with quantification of
      HDL-C using different methods before and after storage. METHODS: Serum samples
      (n=2936) from the Collaborative Atorvastatin Diabetes Study in which HDL-C had
      been determined on 'fresh' samples using the MnCl(2)/heparin method before
      freezing and storage for up to 8 years at -80 degrees C were thawed and HDL-C was
      determined using the Roche direct method. We participated in the Riqas QC
      programme and results obtained for the control serum samples using a CDC-approved
      method were used to generate a regression equation and thus to adjust both
      original results, obtained after precipitation and also to align the direct HDL-C
      results. RESULTS: CDC-aligned HDL-C results for stored samples were lower than
      CDC-aligned HDL-C results before storage (mean [S.E.M.]: 1.41 [0.01] vs. 1.43
      [0.01] mmol/L; P<0.0001, n=2936). Although results after storage tended to be
      lower, there was no significant time-dependent change in the ratio of original to
      stored results for HDL-C. CONCLUSIONS: The study establishes that the Roche 2nd
      generation PEGME method is robust and eminently suitable for determinations of
      HDL-C in stored serum samples.

PMID- 17511979
TI  - Evaluation of an automated soluble transferrin receptor (sTfR) assay on the Roche
      Hitachi analyzer and its comparison to two ELISA assays.
AB  - BACKGROUND: Soluble transferrin receptor (sTfR) assays are currently not
      standardized. This hinders data comparison between studies and also affects the
      use of a recently proposed model to estimate body iron. METHODS: We evaluated the
      analytical performance of a fully automated sTfR immunoturbidimetric assay (Roche
      Diagnostics) and compared it with two ELISA assays (Ramco Laboratories and an in
      house ELISA assay used in the body iron model). RESULTS: The Roche assay showed
      excellent intra- and inter-assay precision (CV<5%). Prolonged exposure of serum
      samples to room temperature and multiple freeze-thaw cycles did not affect sTfR
      concentrations. Receiver-operator characteristic curve analysis demonstrated that
      the Roche assay (area-under-the-curve (AUC)=0.882) was superior to the Ramco
      assay (AUC=0.794) in predicting iron deficiency (defined as serum ferritin <10
      microg/L; P=0.013). Method comparison between the Roche and the two ELISA assays
      showed good correlations (r>0.8); however, sTfR values by the Roche assay were on
      average 30% lower than values obtained with the two ELISA assays. CONCLUSIONS:
      sTfR data measured with an immunoturbidimetric assay can be compared to a
      commonly used ELISA assay, and can be used in the body iron model through
      regression equations obtained in the present study.

PMID- 17511980
TI  - The Micro-Category account of analogy.
AB  - Here, we investigate how activation of mental representations of categories
      during analogical reasoning influences subsequent cognitive processing.
      Specifically, we present and test the central predictions of the "Micro-Category"
      account of analogy. This account emphasizes the role of categories in aligning
      terms for analogical mapping. In a semantic priming paradigm, a four-word analogy
      task was compared to two other four-word tasks. Stimuli were identical in all
      tasks; only the instructions given to participants differed. Participants were
      instructed to identify analogy relations, category relations, or conventionalized
      semantic relations in the four-word sets. After each four-word set, a single
      target word appeared and participants named this word aloud. Target words that
      referred to category relations in the preceding four-word sets were primed as
      strongly when participants identified analogies as when participants identified
      categories, suggesting that activation of category concepts plays an important
      role in analogical thinking. In addition, priming of category-referent words in
      the analogy and category tasks was significantly greater than priming of these
      words when participants identified conventionalized semantic relations. Since
      identical stimuli were used in all conditions, this finding indicates that it is
      the activation of category relations, distinct from any effect of basic semantic
      association, that causes analogical reasoning to prime category-referent words.
      We delineate how the "Micro-Category" account of analogy predicts these phenomena
      and unifies findings from diverse areas of research concerning analogical
      reasoning.

PMID- 17511981
TI  - The homeodomain factor Xanf represses expression of genes in the presumptive
      rostral forebrain that specify more caudal brain regions.
AB  - Early development of the rostral forebrain (RF) in vertebrates is accompanied by
      the inhibition of two homeobox regulators, Otx2 and Pax6 in the rostral sector of
      the anterior neural plate, further giving rise to the RF. However, the precise
      molecular mechanism and meaning of this inhibition is still obscure. We now
      demonstrate that the activity of the Anf homeodomain protein is necessary and
      sufficient for the anterior inhibition of Otx2 and Pax6. Specifically, we show
      that knockdown of the Xenopus laevis Anf, Xanf, by antisense morpholino
      oligonucleotides results in the anterior expansion of Otx2 and Pax6 expression
      into the presumptive RF territory. Furthermore, by overexpressing hormone
      inducible activator- and repressor-fused variants of Xanf in the absence of
      protein synthesis, we present evidence that Xanf can directly downregulate Otx2
      and Pax6 but not the more rostrally expressed Bf1, Bf2, Fgf8 and Nkx2.4. These
      results explain how the inhibitory activity of Xanf can discriminate RF
      regulators in favor of posterior forebrain ones. Assuming that the Anf type of
      homeobox is specific for vertebrates, our data suggest that the emergence of Anf
      in evolution could be a critical event for RF development in vertebrates through
      the elimination of homologues of modern posterior forebrain regulators from the
      rostral sector of the anterior neural plate.

PMID- 17511982
TI  - Association of tibia lead and blood lead with end-stage renal disease: a pilot
      study of African-Americans.
AB  - The association between body lead burden and kidney disease remains
      controversial. Fifty-five African-American end-stage renal disease (ESRD) cases
      and 53 age- and sex-matched African-American controls without known renal disease
      were recruited from Tulane University-affiliated dialysis clinics and out-patient
      clinics, respectively. Blood lead was measured via atomic absorption
      spectrophotometry and tibia lead (a measure of body lead) was measured via
      (109)Cd-based K shell X-ray fluorescence. Median blood lead levels were
      significantly higher among ESRD cases (6 microg/dL) compared to their control
      counterparts (3 microg/dL; P<0.001). Although no participants had overt lead
      poisoning (blood lead > or = 25 microg/dL), seven cases but no controls had blood
      lead levels above 10 microg/dL (P=0.006). The median tibia lead level was 17
      micrograms of lead per gram of bone mineral (microg/g) and 13 microg/g among ESRD
      cases and their control counterparts, respectively (P=0.134). Four ESRD cases
      (7%), but no controls, had a tibia lead level above 40 microg/g (P=0.115) while a
      similar proportion of cases and controls had tibia lead between 20 and 39
      microg/g (33% and 32%, respectively; P=0.726). After adjustment for potential
      confounders, the odds ratios of ESRD associated with a tibia lead > or = 20
      microg/g and each four-fold higher tibia lead (e.g., 5-20 microg/g) were 1.55
      (95% CI: 0.55, 4.41) and 1.88 (95% CI: 0.53, 6.68), respectively. These findings
      support the need for prospective cohort studies of body lead burden and renal
      disease progression.

PMID- 17511983
TI  - Chronic progesterone treatment augments while dehydroepiandrosterone sulphate
      prevents tolerance to ethanol anxiolysis and withdrawal anxiety in rats.
AB  - We have recently shown that the neurosteroid allopregnanolone modulates
      anxiolytic effect of ethanol. In the present report, we attempted to examine
      whether neurosteroids progesterone and dehydroepiandrosterone sulphate (DHEAS),
      which modulate gamma-aminobutyric acid (GABA(A)) receptor function, affects
      development of tolerance to ethanol anxiolysis and withdrawal anxiety. Rats on
      ethanol (6% v/v in nutritionally balanced liquid diet) for prolong period (10
      days) were injected twice daily either with vehicle, progesterone (a precursor of
      allopregnanolone, positive GABA(A) receptor modulator), finasteride (5alpha
      reductase inhibitor) or DHEAS (negative GABA(A) receptor modulator). During this
      period, rats were acutely challenged periodically with ethanol (2 g/kg, i.p., 8%
      w/v) and subjected to the elevated plus maze test. For withdrawal studies,
      similar treatment protocols (except ethanol challenge) were employed and on day
      11, rats were subjected to the elevated plus maze test at different time
      intervals post-ethanol withdrawal. While progesterone significantly advanced the
      development of tolerance to ethanol anxiolysis and enhanced withdrawal anxiety,
      DHEAS and finasteride prevented such behavioral alterations. These data highlight
      the important role played by GABAergic neurosteroids progesterone and DHEAS in
      the development of tolerance to ethanol anxiolysis and withdrawal anxiety in
      rats. Moreover, it points to the potential usefulness of specific neurosteroids
      as targets in the treatment of alcoholism.

PMID- 17511984
TI  - The Rho-kinase inhibitor, fasudil, attenuates diabetic nephropathy in
      streptozotocin-induced diabetic rats.
AB  - This study aimed to investigate the effect of the Rho-kinase inhibitor fasudil on
      the development of diabetic nephropathy and clarify a contribution of the Rho/Rho
      kinase pathway to the pathogenesis of diabetic nephropathy. Diabetes was induced
      in male Sprague-Dawley rats with an intraperitoneal injection of streptozotocin.
      Animals were then divided into the following 4 groups; normal control rats,
      diabetic rats, diabetic rats administered fasudil orally and diabetic rats
      administered fluvastatin (3-hydroxy-methylglutaryl coenzyme A reductase
      inhibitor, statin) orally. After 1 month of treatment, neither fasudil nor statin
      had any influence on blood glucose or blood pressure in diabetic rats. While
      urinary excretion of albumin and 8-hydroxydeoxyguanosine (8-OHdG) was increased
      in diabetic rats, both of these increases were abolished by fasudil and statin.
      Rho activity was enhanced in the renal cortex of diabetic rats compared to normal
      controls, and this enhancement was abolished by statin treatment. Expression of
      transforming growth factor-beta (TGF-beta) and connective tissue growth factor
      (CTGF) mRNA was up-regulated in the renal cortex of diabetic rats, and this was
      abolished by fasudil as well as statin. Expression of NOX4 mRNA (catalytic
      subunit of NAD(P)H oxidase) was up-regulated in the renal cortex of diabetic
      rats, an effect which was also abolished by fasudil as well as statin. The
      present study demonstrates that the Rho/Rho-kinase pathway is involved in up
      regulation of TGF-beta, CTGF and NAD(P)H oxidase in diabetic kidney. We conclude
      that suppression of the Rho/Rho-kinase pathway could be a new strategy for the
      treatment of diabetic nephropathy.

PMID- 17511985
TI  - 17beta-estradiol inhibits angiotensin II-induced collagen synthesis of cultured
      rat cardiac fibroblasts via modulating angiotensin II receptors.
AB  - Circulating endogenous estrogen is considered to be cardiovascular protective,
      but the underlying mechanisms remain obscure. The cardiac fibroblasts, the most
      abundant cell type present in the heart, are responsible for the deposition of
      extracellular matrix. Angiotensin II has been known to stimulate cardiac collagen
      gene expression. The present study was designed to investigate the effect of
      17beta-estradiol on the angiotensin II-induced proliferation and collagen
      synthesis in cultured cardiac fibroblasts by using real-time polymerase chain
      reaction (PCR), Western blot and 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl
      tetrazolium bromide proliferation assay. Angiotensin II increased the cell
      proliferation and synthesis of collagen types I and III. Angiotensin II up
      regulated the gene expression of the angiotensin AT(1) receptor and down
      regulated the gene expression of the angiotensin AT(2) receptor in cardiac
      fibroblasts. The effects of angiotensin II was abolished by the angiotensin AT(1)
      receptor antagonist, losartan, but not by the angiotensin AT(2) receptor
      antagonist, PD 123319. 17beta-estradiol prevented increases in proliferation and
      attenuated the collagen synthesis in response to angiotensin II. The increased
      AT(1) receptor mRNA levels and decreased AT(2) receptor mRNA levels were
      partially reversed by 17beta-estradiol treatment. In conclusion, the down
      regulation of angiotensin AT(1) receptor expression and function is likely to be
      an important mechanism accounting for the inhibitory effect of 17beta-estradiol
      on angiotensin II-stimulated proliferation and collagen synthesis in cardiac
      fibroblasts. This effect may confer at least in part the cardiac protective
      action of 17beta-estradiol under pathological conditions with increased activity
      of the rennin-angiotensin system.

PMID- 17511986
TI  - Commentary to "excessive synchronisation of basal ganglia neurons at 20 Hz slows
      movement in Parkinson's disease".

PMID- 17511987
TI  - Leishmania donovani: inhibition of phagosomal maturation is rescued by nitric
      oxide in macrophages.
AB  - Leishmania donovani promastigotes, the causative agent of visceral leishmaniasis,
      survive inside macrophages by inhibiting phagosomal maturation. The main surface
      glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for parasite
      survival. LPG has several detrimental effects on macrophage function, including
      inhibition of periphagosomal filamentous actin (F-actin) breakdown during
      phagosomal maturation. However, in RAW 264.7 macrophages pre-stimulated with
      lipopolysaccharide (LPS) and interferon gamma (IFNgamma), known to up-regulate
      inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production, L.
      donovani promastigotes are unable to inhibit periphagosomal F-actin breakdown and
      phagosomal maturation proceeds normally. Moreover, the iNOS inhibitor
      aminoguanidine, blocked the positive effects of LPS/IFNgamma suggesting that NO
      is a key player in F-actin remodeling. In conclusion, production of NO by
      stimulated macrophages seems to allow phagosomal maturation following uptake of
      L. donovani promastigotes, suggesting a novel mechanism whereby NO facilitates
      killing of an intracellular pathogen.

PMID- 17511988
TI  - Heme binding properties of heterologously expressed spinach cytochrome b(6):
      implications for transmembrane b-type cytochrome formation.
AB  - In vivo and in vitro requirements for the formation of cytochrome b(6) were
      examined to analyze the mechanisms of transmembrane b-type cytochrome formation.
      After heterologous expression of spinach cytochrome b(6), formation of the holo
      cytochrome was observed within the E. coli inner membrane. The transmembrane
      orientation of cytochrome b(6) appeared not to be critical for heme binding and
      holo-cytochrome formation. Furthermore, in vitro reconstitution of cytochrome
      b(6) was possible under oxidizing as well as under reducing conditions. Taken
      together these observations strongly indicate that transmembrane b-type
      cytochromes can spontaneously assemble in vitro as well as in a membrane.

PMID- 17511989
TI  - Cross-linked SecA dimers are not functional in protein translocation.
AB  - The ATPase SecA is involved in post-translational protein translocation through
      the SecY channel across the bacterial inner membrane. SecA is a dimer that can
      dissociate into monomers with translocation activity. Here, we have addressed
      whether dissociation of the SecA dimer is required for translocation. We show
      that a dimer in which the two subunits are cross-linked by disulfide bridges is
      inactive in protein translocation, translocation ATPase, and binding to a lipid
      bilayer. In contrast, upon reduction of the disulfide bridges, the resulting
      monomers regain these activities. These data support the notion that dissociation
      of SecA dimers into monomers occurs during protein translocation.

PMID- 17511990
TI  - Evidence for a role of glycosphingolipids in CXCR4-dependent cell migration.
AB  - Chemotaxis induction is a major effect evoked by stimulation of the chemokine
      receptor CXCR4 with its sole ligand CXCL12. We now report that treatment of CHP
      100 human neuroepithelioma cells with the glucosylceramide synthase (GCS)
      inhibitor DL-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol inhibits
      CXCR4-dependent chemotaxis. We provide evidence that the phenomenon is not due to
      unspecific effects of the inhibitor employed and that inhibition of GCS neither
      affects total or plasmamembrane CXCR4 expression, nor CXCL12-induced Ca(2+)
      mobilization. The effects of the GCS inhibitor on impairment of CXCL12-induced
      cell migration temporally correlated with a pronounced downregulation of neutral
      glycosphingolipids, particularly glucosylceramide, and with a delayed and more
      moderate downregulation of gangliosides; moreover, exogenously administered
      glycosphingolipids allowed resumption of CXCR4-dependent chemotaxis. Altogether
      our results provide evidence, for the first time, for a role glycosphingolipids
      in sustaining CXCL12-induced cell migration.

PMID- 17511991
TI  - Delayed blastocyst transfer: is the window shutting?
AB  - Data suggest that dyssynchrony between day 6 blastocysts and endometrium may
      impair pregnancy rates in fresh transfer cycles.

PMID- 17511992
TI  - Dienogest inhibits BrdU uptake with G0/G1 arrest in cultured endometriotic
      stromal cells.
AB  - OBJECTIVE: To investigate the effect of dienogest on the proliferation of
      endometriotic stromal cells. DESIGN: Comparative and laboratory study. SETTING:
      University of Tokyo Hospital. PATIENT(S): Endometriotic stromal cells were
      isolated and cultured from ovarian endometriomas of patients undergoing surgery.
      INTERVENTION(S): Dienogest was added to the cultured endometriotic stromal cells.
      MAIN OUTCOME MEASURE(S): 5-Bromo-2'-deoxyuridine (BrdU) incorporation into DNA of
      the endometriotic stromal cells was measured by ELISA. Cell cycle analysis of the
      cultured endometriotic stromal cells was performed by flow cytometry. RESULT(S):
      Dienogest at concentration of 10(-7) M and 10(-6) M significantly inhibited BrdU
      incorporation into DNA at 24 and 48 hours. Dienogest significantly increased the
      cells in G0/G1 phase and reduced the cells in S phase and G2/M phase in 24 and 48
      hours. CONCLUSION(S): The present study indicates that dienogest can inhibit the
      proliferation of the endometriotic stromal cells with G0/G1 arrest, suggesting a
      possible direct effect of dienogest in the treatment of endometriosis.

PMID- 17511993
TI  - Researching human oocyte cryopreservation: ethical issues.
AB  - OBJECTIVE: To evaluate some ethical concerns related to the selection of
      participants for oocyte cryopreservation research. DESIGN: Review of ethical
      issues related to human oocyte cryopreservation research. SETTING: Academic
      medical center. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      A discussion of some ethical concerns surrounding selection of participants for
      oocyte cryopreservation research. RESULT(S): Human oocyte cryopreservation has
      the potential to expand reproductive options for infertile couples. Care needs to
      be taken, however, to carefully select participants in ways that maximizes
      benefits to them and to society and minimizes risks. Infertility programs can do
      so by trying to recruit women who stand to benefit the most from participating in
      oocyte cryopreservation protocols. CONCLUSION(S): Biomedical research is
      necessary to improve current medical therapies. Oocyte cryopreservation can
      increase the flexibility of assisted reproductive programs and offer hope to a
      significant number of infertile couples. Nonetheless, scientific research cannot
      be attentive only to the creation of new knowledge and new technologies; it also
      is inextricably tied to ethical considerations about the well-being of
      participants.

PMID- 17511994
TI  - Experimental evaluation of a time-optimal plug&control strategy.
AB  - In this paper, the application of a time-optimal plug&control strategy is
      discussed. This strategy automatically makes the controller work properly after
      simply connecting it to the control architecture, without further intervention
      from the operator. In particular, a level control task and a temperature control
      task are considered. Implementation problems are addressed and the effectiveness
      of the methodology is shown.

PMID- 17511995
TI  - Delivery and release of nitinol stent in carotid artery and their interactions: a
      finite element analysis.
AB  - Carotid angioplasty and stenting (CAS) has emerged as an effective alternative to
      carotid endarterectomy, and nitinol stents are commonly used in CAS. To evaluate
      biomechanical properties of nitinol carotid stents and their interactions with
      carotid arteries, a finite element method (FEM) model was built which is composed
      of a stenotic carotid tissue, a segmented-design nitinol stent and a sheath. Two
      different stents were considered to show the influence of stent design on the
      stent-vessel interactions. Results show that the superelastic stents were
      delivered into the stenotic vessel lumen through the sheath and self-expanded in
      the internal and common carotid artery. The stent with shorter struts may have
      better clinical results and the different stent designs can cause different
      carotid vessel geometry changes. This FEM can provide a convenient way to test
      and improve biomechanical properties of existing carotid stents and give clues
      for new nitinol carotid stent designs.

PMID- 17511996
TI  - Thermodynamics of micelle formation of alkyltrimethylammonium chlorides from high
      performance electric conductivity measurements.
AB  - Understanding micelle formation requires its complete thermodynamic
      characterization. In this work micellization of the model ionic surfactants
      decyltrimethylammonium chloride (DETAC), dodecyltrimethylammonium chloride (DTAC)
      and tetradecyltrimethylammonium chloride (TTAC) was investigated by high
      performance conductivity measurements, using instrumentation developed in our
      laboratory. The temperature dependence of the critical micelle concentration
      exhibits a minimum characterized by Delta(mic)H(0)=0 (endothermic to exothermic
      process) and the degree of micelle ionization increases slightly with increasing
      temperature. The temperature change of Delta(mic)S(0) indicates that the process
      of micellization is entropically driven. Delta(mic)G(0) is always negative and
      slightly temperature dependent. The temperature dependence of the thermodynamic
      parameters is discussed in terms of the alkyl chain length and nature of the
      counterion. The micellization process is more favourable for surfactants with
      longer alkyl chain length and larger (less hydrated) counterions.

PMID- 17511998
TI  - Sorption of nonionic organic solutes from water to tetraalkylammonium bentonites:
      Mechanistic considerations and application of the Polanyi-Manes potential theory.
AB  - This work describes the role of quaternary alkylammonium amendment length on
      sorption mechanisms of modified bentonites for four nonionic organic compounds;
      benzene, carbon tetrachloride, TCE, and 1,2-DCB. Tetramethyl to tetrabutyl alkyl
      amendments were studied and an important mechanistic shift occurred at the propyl
      chain length for all four solutes studied. Three- and four-carbon-chain
      functional groups on the ammonium cation resulted in a linear, rather than a
      curvilinear isotherm. The uptake on tetrapropyl and tetrabutylammonium clays was
      noncompetitive in binary systems and showed negligible sensitivity to temperature
      variations, indicating the linear isotherms describe a partitioning uptake
      mechanism for these organoclays. The adsorptive organoclays (tetramethyl and
      tetraethylammonium clays) were fit with the Dubinin-Radushkevich equation to
      investigate the application of the Polanyi-Manes potential theory to organoclay
      adsorption. It was found that TCE and carbon tetrachloride, with similar physical
      and chemical characteristics, behaved according to the Polanyi-Manes theory.
      Benzene showed an anomalously high adsorption volume limit, possibly due to dense
      packing in the adsorption space or chemisorption to the short chain alkyl groups.

PMID- 17511997
TI  - Side-chain effect on Langmuir and Langmuir-Blodgett film properties of poly(N
      alkylmethacrylamide)-coated magnetic nanoparticle.
AB  - We report the fabrication of a Langmuir-Blodgett (LB) film of magnetic
      nanoparticles (iron oxide) coated by poly(N-alkylmethacrylamide)s with various
      alkyl chain lengths. The iron oxide nanoparticle (nP) was first modified with a
      reactive polymer, poly(N-hydroxysuccinimide methacrylate) (pSucMA) by applying
      surface initiated atom transfer radical polymerization (ATRP) technique. Then the
      succinimide group was replaced by various amine derivatives. The monolayer
      behaviors of the resultant nanoparticles, as modified by various poly(N
      alkylmethacrylamide)s, such as poly(octylmethacrylamide) (pOMA),
      poly(dodecylmethacrylamide) (pDDMA), polytetradecylmethacrylamide (pTDMA), and
      poly(hexadecylmethacrylamide) (pHDMA) were elucidated using surface pressure-area
      isotherm measurements. Results show that pTDMA-modified nanoparticles (nP-pTDMA)
      exhibit the highest collapse pressure with a steeply rising surface pressure. The
      monolayer of nP-pTDMA on the water surface was transferred onto a solid substrate
      using the LB technique. Atomic force microscopy (AFM) images of the transferred
      LB film show that nP-pTDMA particles form a uniform nanoparticle monolayer. The
      LB film of nP-pTDMA with multilayers was fabricated through sequential transfer
      of the particles monolayer onto the substrate surface. The resultant LB film of
      nanoparticles shows a superparamagnetic behavior at room temperature.

PMID- 17511999
TI  - Stable cluster formation in aqueous suspensions of iron oxyhydroxide
      nanoparticles.
AB  - Metal oxide and oxyhydroxide nanoparticles are important components of natural
      aqueous systems and have application in photocatalysis. Uncoated (oxyhydr)oxide
      nanoparticles can form charge-stabilized colloids in water, but the precise
      regimes of dispersion and aggregation have been determined for very few
      nanomaterials. We studied the colloidal behavior of approximately 6 nm
      nanoparticles of iron oxyhydroxide (FeOOH), a common natural nanoscale colloid,
      and found that these nanoparticles formed stable suspended clusters under a range
      of aqueous conditions. Light and X-ray scattering methods show that suspended
      fractal nanoclusters are formed between pH 5 and 6.6 with well-defined maximum
      diameters that can be varied from 25 nm to approximately 1000 nm. The
      nanoclusters retain a very high surface area, and persist in suspension for at
      least 10 weeks in solution. The process is partially reversible because optically
      transparent suspensions are regained when nanoparticles that aggregated and
      settled at pH >7 are adjusted to pH 4 without stirring. However, completely
      redispersed nanoparticles are not obtained even after one month. Because
      nanocluster formation is controlled predominantly by surface charge, we
      anticipate that many metal oxide and other inorganic nanoparticles will exhibit
      equivalent cluster-forming behavior. Our results indicate that natural
      nanoparticles could form stable nanoclusters in groundwater that are likely to be
      highly mobile, with implications for the long-range transport of surface sorbed
      contaminants.

PMID- 17512000
TI  - Effect of anionic surfactants on synthesis and self-assembly of silica colloidal
      nanoparticles.
AB  - Effects of the anionic surfactants, sodium dodecyl sulfate and sodium oleate, on
      the formation and properties of silica colloidal nanoparticles were investigated.
      At a concentration of approximately 1 x 10(-3) M, adsorption of anionic
      surfactants increased particle size, monodispersity, and negative surface charge
      density of synthesized silica particles. As uniformity of particle size and
      particle-particle interactions increase, colloidal photonic crystals readily self
      assemble without extensive washing of the synthesized silica nanoparticles. The
      photonic crystals diffract light in the visible region according to Bragg's law.
      The assembled colloidal particle arrays exhibit a face-centered cubic structure
      in dried thin films. This study offers a new approach for producing ordered
      colloidal silica thin films.

PMID- 17512001
TI  - Different defense strategies of Dendrolimus pini, Galleria mellonella, and
      Calliphora vicina against fungal infection.
AB  - The resistance of Galleria mellonella, Dendrolimus pini, and Calliphora vicina
      larvae against infection by the enthomopathogen Conidiobolus coronatus was shown
      to vary among the studied species. Exposure of both G. mellonella and D. pini
      larvae to the fungus resulted in rapid insect death, while all the C. vicina
      larvae remained unharmed. Microscopic studies revealed diverse responses of the
      three species to the fungal pathogen: (1) the body cavities of D. pini larvae
      were completely overgrown by fungal hyphae, with no signs of hemocyte response,
      (2) infected G. mellonella larvae formed melanotic capsules surrounding the
      fungal pathogen, and (3) the conidia of C. coronatus did not germinate on the
      cuticle of C. vicina larvae. The in vitro study on the degradation of the insect
      cuticle by proteases secreted by C. coronatus revealed that the G. mellonella
      cuticle degraded at the highest rate. The antiproteolytic capacities of insect
      hemolymph against fungal proteases correlated well with the insects'
      susceptibility to fungal infection. The antiproteolytic capacities of insect
      hemolymph against fungal proteases correlated well with the insects'
      susceptibility to fungal infection. Of all the tested species, only plasmatocytes
      exhibited phagocytic potential. Exposure to the fungal pathogen resulted in
      elevated phagocytic activity, found to be the highest in the infected G.
      mellonella. The incubation of insect hemolymph with fungal conidia and hyphae
      revealed diverse reactions of hemocytes of the studied insect species. The
      encapsulation potential of D. pini hemocytes was low. Hemocytes of G. mellonella
      showed a high ability to attach and encapsulate fungal structures. Incubation of
      C. vicina hemolymph with C. coronatus did not result in any hemocytic response.
      Phenoloxidase (PO) activity was found to be highest in D. pini hemolymph,
      moderate in G. mellonella, and lowest in the hemolymph of C. vicina. Fungal
      infection resulted in a significant decrease of PO activity in G. mellonela
      larvae, while that in the larvae of D. pini remained unchanged. PO activity in C.
      vicina exposed to fungus slightly increased. The lysozyme-like activity increased
      in the plasma of all three insect species after contact with the fungal pathogen.
      Anti E. coli activity was detected neither in control nor in infected D. pini
      larvae. No detectable anti E. coli activity was found in the control larvae of G.
      mellonella; however, its exposure to C. coronatus resulted in an increase in the
      activity to detectable level. In the case of C. vicina exposure to the fungus,
      the anti E. coli activity was significantly higher than in control larvae. The
      defense mechanisms of D. pini (species of economic importance in Europe) are
      presented for the first time.

PMID- 17512002
TI  - Cloning and characterization of two Campoletis chlorideae ichnovirus vankyrin
      genes expressed in parasitized host Helicoverpa armigera.
AB  - Polydnaviruses, symbionts of parasitic ichneumonid (ichnoviruses, IVs) and
      braconid (bracoviruses, BVs), are injected into hosts along with wasp eggs.
      Within the host, PDV genes are expressed and their products function to alter
      lepidopteran host physiology and enable endoparasitoid development. In the
      present study, we describe two Campoletis chlorideae ichnovirus (CcIV) viral
      ankyrin (vankyrin) genes and their transcription. The CcIV vankyrin genes possess
      ankyrin repeat domains that resemble the inhibitory domains of the Drosophila
      melanogaster NF-kappaB transcription factor inhibitor (IkappaB) cactus. The
      expression of CcIV vankyrin genes could be detected in Helicoverpa armigera
      during the whole course of parasitization with two expression peaks, 30 min post
      parasitization (p.p.) and 2 days p.p. Our data indicate that the CcIV vankyrin
      genes are differentially expressed in the tissues of parasitized hosts and both
      are mainly expressed in hemocytes. The temporal and spatial variation in
      expression of the two CcIV vankyrin genes suggests that CcIV vankyrin genes could
      be involved in early protection of parasitoid eggs from host cellular immune
      response by suppressing NF-kappaB signaling cascades, thereby altering
      development and immune responses of parasitized lepidopteran hosts.

PMID- 17512003
TI  - Molecular modeling of the binding of pheromone biosynthesis activating
      neuropeptide to its receptor.
AB  - Moth sex-pheromone biosynthesis follows a circadian cycle, which is cued by the
      release of the neurohormone pheromone biosynthesis activating neuropeptide (PBAN)
      to the hemolymph. PBAN binds to a G protein-coupled receptor (GPCR), in pheromone
      glands, (PG) initially identified by us in Helicoverpa zea moths (HezPBAN-R). In
      this study, the sequences of the seven transmembrane helices of HezPBAN-R were
      identified, built, packed and oriented correctly after multiple sequence
      alignment of the HezPBAN-R and several other GPCRs using the X-ray structure of
      rhodopsin as a template. Molecular dynamics simulations were run on three
      different beta-turn types of the C-terminal hexapeptide of PBAN and the results
      clustered into 12 structurally distinct groups. The lowest energy conformation
      from each group was used for computer-simulated docking with the model of the
      HezPBAN-R. Highest scoring complexes were examined and putative binding sites
      were identified. Experimental studies, using in vitro PG, revealed lower levels
      of pheromonotropic activity when challenged with pyrokinin-like peptides than
      with HezPBAN as ligand. Thus, the Drosophila melanogaster pyrokinin-1 receptor
      (CG9918) was chosen to create chimera receptors by exchanging between the three
      extracellular loops of the HezPBAN-R and the CG9918 for in silico mutagenesis
      experiments. The predicted docking model was validated with experimental data
      obtained from expressed chimera receptors in Sf9 cells.

PMID- 17512004
TI  - Vertical transmission of Nosema fumiferanae (Microsporidia: Nosematidae) and
      consequences for distribution, post-diapause emergence and dispersal of second
      instar larvae of the spruce budworm, Choristoneura fumiferana (Clem.)
      (Lepidoptera: Tortricidae).
AB  - We examined vertical transmission of Nosema fumiferanae in the eastern spruce
      budworm, Choristoneura fumiferana (Clem.) (Lepidoptera: Tortricidae), and how it
      affects overwintering distribution and survival and spring emergence and
      dispersal of second-instar larvae in outbreak populations. Females containing 5.0
      x 10(5) spores or more consistently produced 100% infected progeny. Transmission
      efficiency was still 50% at burdens as low as 0.2 x 10(5) spores per moth.
      Infection intensity in offspring increased with maternal spore load but became
      highly variable above 25 x 10(5) spores per female. Nosema multiplied in second
      instars for at least 1 month after they entered dormancy, regardless of
      temperature (2 degrees C versus 21 degrees C). Infection did not affect the
      distribution of overwintering larvae in a white spruce canopy. Dormancy survival
      between late-summer and the following spring was lower in families from infected
      females and was negatively correlated with larval infection intensity. Infection
      delayed larval emergence from hibernacula in the spring and resulted in delayed
      dispersal of emerged larvae, at least when parasite prevalence and infection
      intensities were high. Infected larvae were less successful in establishing
      feeding sites after dispersal. Our results underscore the potential of Nosema
      infection to negatively affect processes early in the budworm life cycle.

PMID- 17512005
TI  - The structure of human thioredoxin reductase 1 provides insights into C-terminal
      rearrangements during catalysis.
AB  - Human thioredoxin reductase (hTrxR) is a homodimeric flavoprotein crucially
      involved in the regulation of cellular redox reactions, growth and
      differentiation. The enzyme contains a selenocysteine residue at its C-terminal
      active site that is essential for catalysis. This redox center is located on a
      flexible arm, solvent-exposed and reactive towards electrophilic inhibitors, thus
      representing a target for antitumor drug development. During catalysis reducing
      equivalents are transferred from the cofactor NADPH to FAD, then to the N
      terminal active site cysteine residues and from there to the flexible C-terminal
      part of the other subunit to be finally delivered to a variety of second
      substrates at the molecule's surface. Here we report the first crystal structure
      of hTrxR1 (Sec-->Cys) in complex with FAD and NADP(+) at a resolution of 2.8 A.
      From the crystals three different conformations of the carboxy-terminal arm could
      be deduced. The predicted movement of the arm is facilitated by the concerted
      action of the three side-chain residues of N418, N419 and W407, which act as a
      guiding bar for the C-terminal sliding process. As supported by previous kinetic
      data, the three visualized conformations might reflect different stages in
      enzymatic catalysis. Comparison with other disulfide reductases including human
      glutathione reductase revealed specific inhibitor binding sites in the
      intersubunit cavity of hTrxR that can be exploited for structure-based inhibitor
      development.

PMID- 17512006
TI  - Structural insights into the second step of RNA-dependent cysteine biosynthesis
      in archaea: crystal structure of Sep-tRNA:Cys-tRNA synthase from Archaeoglobus
      fulgidus.
AB  - In the ancient organisms, methanogenic archaea, lacking the canonical cysteinyl
      tRNA synthetase, Cys-tRNA(Cys) is produced by an indirect pathway, in which O
      phosphoseryl-tRNA synthetase ligates O-phosphoserine (Sep) to tRNA(Cys) and Sep
      tRNA:Cys-tRNA synthase (SepCysS) converts Sep-tRNA(Cys) to Cys-tRNA(Cys). In this
      study, the crystal structure of SepCysS from Archaeoglobus fulgidus has been
      determined at 2.4 A resolution. SepCysS forms a dimer, composed of monomers
      bearing large and small domains. The large domain harbors the seven-stranded beta
      sheet, which is typical of the pyridoxal 5'-phosphate (PLP)-dependent enzymes. In
      the active site, which is located near the dimer interface, PLP is covalently
      bound to the side-chain of the conserved Lys209. In the proximity of PLP, a
      sulfate ion is bound by the side-chains of the conserved Arg79, His103, and
      Tyr104 residues. The active site is located deep within the large, basic cleft to
      accommodate Sep-tRNA(Cys). On the basis of the surface electrostatic potential,
      the amino acid residue conservation mapping, the position of the bound sulfate
      ion, and the substrate amino acid binding manner in other PLP-dependent enzymes,
      a binding model of Sep-tRNA(Cys) to SepCysS was constructed. One of the three
      strictly conserved Cys residues (Cys39, Cys42, or Cys247), of one subunit may
      play a crucial role in the catalysis in the active site of the other subunit.

PMID- 17512007
TI  - Mechanism for de novo RNA synthesis and initiating nucleotide specificity by t7
      RNA polymerase.
AB  - DNA-directed RNA polymerases are capable of initiating synthesis of RNA without
      primers, the first catalytic stage of initiation is referred to as de novo RNA
      synthesis. De novo synthesis is a unique phase in the transcription cycle where
      the RNA polymerase binds two nucleotides rather than a nascent RNA polymer and a
      single nucleotide. For bacteriophage T7 RNA polymerase, transcription begins with
      a marked preference for GTP at the +1 and +2 positions. We determined the crystal
      structures of T7 RNA polymerase complexes captured during the de novo RNA
      synthesis. The DNA substrates in the structures in the complexes contain a common
      Phi 10 duplex promoter followed by a unique five base single-stranded extension
      of template DNA whose sequences varied at positions +1 and +2, thereby allowing
      for different pairs of initiating nucleotides GTP, ATP, CTP or UTP to bind. The
      structures show that the initiating nucleotides bind RNA polymerase in locations
      distinct from those described previously for elongation complexes. Selection bias
      in favor of GTP as an initiating nucleotide is accomplished by shape
      complementarity, extensive protein side-chain and strong base-stacking
      interactions for the guanine moiety in the enzyme active site. Consequently, an
      initiating GTP provides the largest stabilization force for the open promoter
      conformation.

PMID- 17512008
TI  - Observation of intersubunit movement of the ribosome in solution using FRET.
AB  - Protein synthesis is believed to be a dynamic process, involving structural
      rearrangements of the ribosome. Cryo-EM reconstructions of certain elongation
      factor G (EF-G)-containing complexes have led to the proposal that translocation
      of tRNA and mRNA through the ribosome, from the A to P to E sites, is accompanied
      by a rotational movement between the two ribosomal subunits. Here, we have used
      Forster resonance energy transfer (FRET) to monitor changes in the relative
      orientation of the ribosomal subunits in different complexes trapped at
      intermediate stages of translocation in solution. Binding of EF-G to the ribosome
      in the presence of the non-hydrolyzable GTP analogue GDPNP or GTP plus fusidic
      acid causes an increase in the efficiency of energy transfer between fluorophores
      introduced into proteins S11 in the 30 S subunit and L9 in the 50 S subunit, and
      a decrease in energy transfer between S6 and L9. Similar anti-correlated changes
      in energy transfer occur upon binding the GTP-requiring release factor RF3. These
      changes are consistent with the counter-clockwise rotation of the 30 S subunit
      relative to the 50 S subunit observed in cryo-EM studies. Reaction of ribosomal
      complexes containing the peptidyl-tRNA analogues N-Ac-Phe-tRNAPhe, N-Ac-Met
      tRNAMet or f-Met-tRNAfMet with puromycin, conditions favoring movement of the
      resulting deacylated tRNAs into the P/E hybrid state, leads to similar changes in
      FRET. Conversely, treatment of a ribosomal complex containing deacylated and
      peptidyl-tRNAs bound in the A/P and P/E states, respectively, with EF-G.GTP
      causes reversal of the FRET changes. The use of FRET has enabled direct
      observation of intersubunit movement in solution, provides independent evidence
      that formation of the hybrid state is coupled to rotation of the 30 S subunit and
      shows that the intersubunit movement is reversed during the second step of
      translocation.

PMID- 17512009
TI  - Nylon-oligomer degrading enzyme/substrate complex: catalytic mechanism of 6
      aminohexanoate-dimer hydrolase.
AB  - We performed X-ray crystallographic analyses of 6-aminohexanoate-dimer hydrolase
      (Hyb-24DN), an enzyme responsible for the degradation of nylon-6, an industry by
      product, and of a complex between Hyb-24DN-A(112) (S112A-mutant of Hyb-24DN) and
      6-aminohexanoate-linear dimer (Ald) at 1.58 A and 1.4 A resolution, respectively.
      In Hyb-24DN, Asp181-O(delta) forms hydrogen bonds with Tyr170-O(eta), -two of the
      catalytic and binding amino acids, and a loop between Asn167 and Val177. This
      state is the so-called open form, allowing its substrate to bind in the space
      between the loop and catalytic residues. Upon substrate binding (in Hyb-24DN
      A(112)/Ald complex), the loop is shifted 4.3 A at Tyr170-C(alpha), and the side
      chain of Tyr170 is rotated. By the combined effect, Tyr170-O(eta) moves a total
      of 10.5 A, resulting in the formation of hydrogen bonds with the nitrogen of
      amide linkage in Ald (closed form). In addition, electrostatic interaction
      between Asp181-O(delta) and the amino group in Ald stabilizes the substrate
      binding. We propose here that the enzyme catalysis proceeds according to the
      following steps: (i) Ald-induced transition from open to closed form, (ii)
      nucleophilic attack of Ser112 to Ald and formation of a tetrahedral intermediate,
      (iii) formation of acyl enzyme and transition to open form, (iv) deacylation.
      Amino acid substitutions reducing the enzyme/Ald interaction at positions 181 or
      170 drastically decreased the Ald-hydrolytic activity, but had very little effect
      on esterolytic activity, suggesting that esterolytic reaction proceeds regardless
      of conversion. Present models illustrate why new activity against the nylon
      oligomer has evolved in an esterase with beta-lactamase folds, while retaining
      the original esterolytic functions.

PMID- 17512010
TI  - Rebleeding from ruptured intracranial aneurysms in North Eastern Province of
      Japan. A cooperative study.
AB  - OBJECT: Rebleeding from ruptured intracranial aneurysms is a major cause of death
      and disability. With regard to the factors that precipitate the rebleeding and
      influence the time course after initial bleeding, previous reports differ in
      their results, and the number of patients investigated was not sufficient for
      valid conclusions. This study was thus designed to clarify the factors related to
      rebleeding from ruptured intracranial aneurysms in a large group of patients of
      the North Eastern Province of Japan. METHODS: We found 181 patients with
      rebleeding after hospitalization among 5612 cases of ruptured intracranial
      aneurysms from January 1997 to December 2001 in 33 major hospitals in the North
      Eastern Province of Japan. We analyzed the data with respect to the time course
      after bleeding and rebleeding, the arterial blood pressure, the situation when
      rebleeding occurred, the methods of neuroimaging, the level of consciousness, the
      treatment and the outcome. RESULTS: Of 181 patients who were hospitalized,
      rebleeding occurred in 65 (35.9%) within 3 h and 88 (48.6%) within 6 h after the
      initial subarachnoid hemorrhage (SAH). The consciousness level before the
      rebleeding varied widely in distribution, but belonged to the drowsiness or less
      [Japan coma scale (JCS) single-digit] in 83 patients (45.8%), but after
      rebleeding, JCS triple-digits (semicoma to coma) included 152 patients (84.0%).
      Systolic arterial blood pressure prior to rebleeding was most commonly between
      120 and 140 mmHg. Rebleeding did occur more frequently during angiography
      (totally 29 patients, 20%) and much less frequently during 3D-CTA and MRA
      procedures (a single case). Treatment consisted of aneurysm neck clipping in 72
      patients (40.0%), endovascular therapy with coils in 4 patients (2.2%) and
      conservative ones in 103 patients (56.9%). As to outcome, 109 patients with
      rebleeding (60.2%) died in 3 months following initial SAH. CONCLUSION: Rebleeding
      occurs more frequently in the earlier period after the initial SAH than
      previously believed. Thus, more aggressive pharmacologically induced systemic
      arterial hypotension appears to be important for preventing rebleeding but
      ultimate outcome of more aggressive hypotension is yet to be determined. If
      feasible, in order to avoid catheter-angiography related rebleeding, evaluations
      solely with 3D-CTA and MRA should be in consideration and earlier surgical
      intervention seems essential as rebleeding does occur often within the first 3 h
      of onset.

PMID- 17512011
TI  - Treatment of spinocerebellar ataxia with buspirone.
AB  - Preliminary data suggest potential benefit of 5-HT receptor agonists in the
      treatment of ataxias. We studied the effects of buspirone in a cohort of twenty
      patients with spinocerebellar ataxia (SCA). Twenty patients were treated in this
      double-blind, placebo controlled, cross-over trial with either buspirone HCl 30
      mg twice daily or placebo for 3 months. Buspirone was not shown to be superior to
      placebo in the treatment of patients with SCA.

PMID- 17512012
TI  - Sudden bilateral blindness in Wernicke's encephalopathy: case report and review
      of the literature.
AB  - We report on a patient suffering from bilateral sudden blindness as initial
      symptom of Wernicke's encephalopathy (WE). A 37-year-old male alcoholic was
      admitted to a psychiatric clinic because of excessive alcohol consumption (3.4
      per thousand). 24 h later he developed acute bilateral blindness with no light
      perception, downbeat nystagmus, bilateral ocular abduction deficits, cerebellar
      ataxia as well as a slight psychomotor slowing and mild disorientation. MRI
      including diffusion-weighted imaging and MR-angiography 3 h after symptom onset
      did not reveal findings suggestive for ischemic stroke. Immediate iv-application
      of thiamine led to a nearly complete remission of the neuroophthalmologic
      symptoms within 12 h. Although we critically discuss other potential etiologies,
      we conclude that the complex clinical picture with initial sudden blindness is an
      unusual presentation of WE.

PMID- 17512013
TI  - Watermelon stripes. A case for the clonal mosaic model in plants.

PMID- 17512015
TI  - Anesthesia for laparoscopic donor nephrectomy: is nitrous oxide contraindicated?
AB  - PURPOSE: We performed this study to test the hypothesis that nitrous oxide
      produces clinically significant bowel distention during laparoscopic abdominal
      surgery. MATERIALS AND METHODS: Laparoscopic kidney donors were randomized into 2
      groups. Group 1 received N2O and oxygen inhalation through anesthesia, and group
      2 received a mixture of air and oxygen. All patients received the same
      preanesthetic and anesthetic medications. The surgeon was blinded to the use of
      N2O. The surgeon was given the option to discontinue N2O use (if it was used) if
      he/she thought that the bowel distention was increasing surgical risk.
      Postoperative data were collected on bowel symptoms, pain and recovery. RESULTS:
      A total of 28 patients were enrolled in the study, 12 of whom received N2O (group
      1) and 16 who did not receive N2O (group 2). Mild to moderate bowel distention
      was reported by the surgeons in 6 patients (50%) in group 1 and 1 patient only in
      group 2 (6%, p=0.007). Severe bowel distention was encountered in 4 patients, 3
      of whom received N2O (25% of group 1). Nausea and vomiting on postoperative day 1
      was reported by 50% of patients in group 1 and 25% of group 2. There was no
      difference in the pain scores between the 2 groups. No intraoperative or
      postoperative complications were encountered. CONCLUSIONS: The use of N2O
      anesthetic causes bowel distention in 50% of abdominal laparoscopic donor
      nephrectomy operations. The distention was severe enough to interfere with the
      progress of surgery in 25% of cases and the use of N2O had to be discontinued.

PMID- 17512017
TI  - Protective effect of ursodeoxycholic acid on liver mitochondrial function in rats
      with alloxan-induced diabetes: link with oxidative stress.
AB  - We investigated the effects of ursodeoxycholic acid (UDCA) on mitochondrial
      functions and oxidative stress and evaluated their relationships in the livers of
      rats with alloxan-induced diabetes. Diabetes was induced in male Wistar rats by a
      single alloxan injection (150 mg kg(-1) b.w., i.p.). UDCA (40 mg kg(-1) b.w.,
      i.g., 30 days) was administered from the 5th day after the alloxan treatment.
      Mitochondrial functions were evaluated by oxygen consumption with Clark oxygen
      electrode using succinate, pyruvate+malate or palmitoyl carnitine as substrates
      and by determination of succinate dehydrogenase and NADH dehydrogenase
      activities. Liver mitochondria were used to measure chemiluminiscence enhanced by
      luminol and lucigenin, reduced liver glutathione and the end-products of lipid
      peroxidation. The activities of both NADH dehydrogenase and succinate
      dehydrogenase as well as the respiratory control (RC) value with all the
      substrates and the ADP/O ratio with pyruvate+malate and succinate as substrates
      were significantly decreased in diabetic rats. UDCA developed the beneficial
      effect on the mitochondrial respiration and oxidative phosphorylation parameters
      in alloxan-treated rats, whereas the activities of mitochondrial enzymes were
      increased insignificantly after the administration of UDCA. The contents of polar
      carbonyls and MDA as well as the chemiluminescence with luminol were elevated in
      liver mitochondria of diabetic rats. The treatment with UDCA normalized all the
      above parameters measured except the MDA content. UDCA administration prevents
      mitochondrial dysfunction in rats treated with alloxan and this process is
      closely connected with inhibition of oxidative stress by this compound.

PMID- 17512016
TI  - hSMR3A as a marker for patients with erectile dysfunction.
AB  - PURPOSE: We recently reported that Vcsa1 is one of the most down-regulated genes
      in the corpora of rats in 3 distinct models of erectile dysfunction. Since gene
      transfer of plasmids expressing Vcsa1 or intracorporeal injection of its mature
      peptide product sialorphin into the corpora of aging rats was shown to restore
      erectile function, we proposed that the Vcsa1 gene has a direct role in erectile
      function. To determine if similar changes in gene expression occur in the corpora
      of human subjects with erectile dysfunction we identified a human homologue of
      Vcsa1 (hSMR3A) and determined the level of expression of hSMR3A in patients.
      MATERIALS AND METHODS: hSMR3A was identified as a homologue of Vcsa1 by searching
      protein databases for proteins with similarity. hSMR3A cDNA was generated and
      subcloned into the plasmid pVAX to generate pVAX-hSMR3A. pVAX-hSMR3A (25 or 100
      microg) was intracorporeally injected into aging rats. The effect on erectile
      physiology was compared histologically and by measuring intracorporeal
      pressure/blood pressure with controls treated with the empty plasmid pVAX. Total
      RNA was extracted from human corporeal tissue obtained from patients undergoing
      previously scheduled penile surgery. Patients were grouped according to normal
      erectile function (3), erectile dysfunction and diabetes (5) and patients without
      diabetes but with erectile dysfunction (5). Quantitative reverse-transcriptase
      polymerase chain reaction was used to determine the hSMR3A expression level.
      RESULTS: Intracorporeal injection of 25 microg pVAX-hSMR3A was able to
      significantly increase the intracorporeal pressure-to-blood pressure ratio in
      aging rats compared to age matched controls. Higher amounts (100 microg) of gene
      transfer of the plasmid caused less of an improvement in the intracorporeal
      pressure-to-blood pressure ratio compared to controls, although there was
      histological and visual evidence that the animals were post-priapitic. These
      physiological effects were similar to previously reported effects of
      intracorporeal injection of pVAX-Vcsa1 into the corpora of aging rats,
      establishing hSMR3A as a functional homologue of Vcsa1. More than 10-fold down
      regulation in hSMR3A transcript expression was observed in the corpora of
      patients with vs without erectile dysfunction. In patients with diabetes
      associated and nondiabetes associated erectile dysfunction hSMR3A expression was
      found to be down-regulated. CONCLUSIONS: These results suggest that hSMR3A can
      act as a marker for erectile dysfunction associated with diabetic and nondiabetic
      etiologies. Given that our previous studies demonstrated that gene transfer of
      the Vcsa1 gene and intracorporeal injection of its protein product in rats can
      restore erectile function, these results suggest that therapies that increase the
      hSMR3A gene and product expression could potentially have a positive impact on
      erectile function.

PMID- 17512018
TI  - Effects of leucine and phenylalanine supplementation during intermittent periods
      of food restriction and refeeding in adult rats.
AB  - Although many studies have shown that amino acid ingestion acutely stimulates
      protein anabolism, only few studies have investigated whether long-term
      supplementation promotes changes in body composition. We therefore tested the
      hypothesis that l-leucine (LEU) and l-phenylalanine (PHE) supplementation might
      have a positive impact on the body composition of rats submitted to intermittent
      periods of food restriction and refeeding (weight cycling or WC). The WC protocol
      comprised three cycles, each consisting of 1 week of 50% food restriction
      followed by 2 weeks of ad libitum ingestion. The groups submitted to WC ingested
      the control diet (WC-CON) or the diet supplemented with LEU+PHE (WC-AA). A pair
      fed group receiving the control diet (PF-CON) was used as a reference for the
      effects of WC. Although food intake was the same in all groups, higher body
      weight and energy efficiency were observed in the WC-AA group compared to the PF
      CON and WC-CON groups although not significantly in relation to the latter. These
      results were the consequence of a significant increase of lean body mass and body
      protein content in the WC-AA group compared to the PF-CON and WC-CON groups. The
      WC-CON and WC-AA groups presented 36.1% and 18.9% more body fat, respectively,
      than the PF-CON group but this difference was not significant. Neither fasting
      insulin nor glucose concentration nor postprandial insulin secretion was
      significantly affected by the supplemented diet. In conclusion, supplementation
      with LEU+PHE improved the body composition profile of rats submitted to WC,
      mainly by increasing lean body mass and body protein content.

PMID- 17512019
TI  - Involvement of prostaglandin E receptor EP3 subtype in duodenal bicarbonate
      secretion in rats.
AB  - We investigated the involvement of prostaglandin E (PGE) receptor subtype EP3 in
      the regulatory mechanism of duodenal HCO(3)(-) secretion in rats. A proximal
      duodenal loop or a chambered stomach was perfused with saline, and HCO(3)(-)
      secretion was measured using a pH-stat method and by adding 2 mM HCl. Mucosal
      acidification was achieved through 10 min of exposure to 10 mM HCl in the
      duodenum or 100 mM HCl in the stomach. Various EP agonists or the EP4 antagonist
      were given i.v., while the EP1 or EP3 antagonist was given s.c. or i.d.,
      respectively. Sulprostone (EP1/EP3 agonists) stimulated duodenal HCO(3)(-)
      secretion in a dose-dependent manner, and this response was inhibited by AE5-599
      (EP3 antagonist) but not AE3-208 (EP4 antagonist). AE1-329 (EP4 agonist) also
      increased duodenal HCO(3)(-) secretion, and this action was inhibited by AE3-208
      but not AE5-599. The response to PGE(2) or acidification in the duodenum was
      partially attenuated by AE5-599 or AE3-208 alone but completely abolished by the
      combined administration. Duodenal damage caused by mucosal perfusion with 150 mM
      HCl for 4 h was worsened by pretreatment with AE5-599 and AE3-208 as well as
      indomethacin and further aggravated by co-administration of these antagonists.
      Neither the EP3 nor EP4 antagonist had any effect on the gastric response induced
      by PGE(2) or acidification. These results clearly demonstrate the involvement of
      EP3 receptors, in addition to EP4 receptors, in the regulation of duodenal
      HCO(3)(-) secretion as well as the maintenance of the mucosal integrity of the
      duodenum against acid injury.

PMID- 17512020
TI  - Chlorpromazine exacerbates hepatic insulin sensitivity via attenuating insulin
      and leptin signaling pathway, while exercise partially reverses the adverse
      effects.
AB  - Investigated in this study are the effects and mechanisms of exercise and
      chlorpromazine (CPZ), a widely used conventional antipsychotic drug, on the
      hepatic insulin sensitivity of 90% pancreatectomized (Px) male Sprague-Dawley
      rats. The Px diabetic rats were provided with 0, 5, or 50 mg CPZ per kg of body
      weight (No-CPZ, LCPZ, or HCPZ) for 8 weeks, and half of each group had regular
      exercise. LCPZ did not exacerbate hepatic insulin sensitivity through insulin and
      leptin signaling in diabetic rats. However, HCPZ decreased whole-body glucose
      infusion rates in hyperinsulinemic clamped states, but not whole-body glucose
      uptake. This was due to the elevated hepatic glucose output in hyperinsulinemic
      states. The decreased hepatic insulin sensitivity was associated with insulin
      receptor substrate-2 (IRS2) protein levels in the liver. Decreased IRS2 levels
      attenuated hepatic insulin and leptin signaling pathways in hyperinsulinemic
      states, which elevated glucose production by inducing phosphoenolpyruvate
      carboxykinase expression. Long-term exercise recovered hepatic insulin
      sensitivity attenuated by HCPZ to reduce the hepatic glucose output in
      hyperinsulinemic clamped states. This recovery was related to enhanced insulin
      and leptin signaling via increased IRS2 gene and protein levels by activating the
      cAMP responding element-binding protein, but exercise improved only insulin
      signaling. In conclusion, HCPZ exacerbates hepatic insulin action by attenuating
      insulin and leptin signaling in type 2 diabetic rats, while regular exercise
      partially reverses the attenuation of hepatic insulin sensitivity by improving
      insulin signaling. Enhancement of insulin and leptin signaling through an
      induction of IRS2 may play an important role in improving hepatic glucose
      homeostasis.

PMID- 17512021
TI  - Emodin suppresses interleukin-1beta induced mesangial cells proliferation and
      extracellular matrix production via inhibiting P38 MAPK.
AB  - Previous findings indicate that emodin has anti-proliferation and anti-fibrosis
      effects on several cell lines. In this study, we investigated the effects of
      emodin on IL-1beta induced proliferation of mesangial cells (MCs) and on their
      production of extracellular matrix (ECM), and explored the possible mechanisms.
      To test the therapeutic effect of emodin on progressive renal disease, we
      administered emodin to rats in renal failure models induced by subtotal
      nephrectomy, the renal function was analyzed. Our results showed emodin
      significantly suppressed IL-1beta induced MC proliferation and arrested the cell
      cycle progress in vitro. Fibronectin and collagen IV production by MC were
      significantly reduced after emodin treatment. P38 mRNA, protein levels of P-P38,
      P-MKK3/6 and P-MKK4 were quantified. We observed no alterations of P38 expression
      and P-MKK4 protein content; however, protein levels of P-P38 and P-MKK3/6
      significantly decreased after emodin treatment. In the renal failure models,
      after administration of emodin for eight weeks, the rat renal lesions were
      significantly ameliorated, as evidenced by the decreased blood creatinine, urea,
      and the 24-hour urine protein. In conclusion, emodin suppresses IL-1beta induced
      MC proliferation and ECM production in vitro. We hypothesize that this is
      achieved by inactivating MKK3/6 and P38. Emodin ameliorates renal failure in
      subtotal nephrectomized rats, which suggests a potential role of emodin in the
      treatment of progressive renal diseases.

PMID- 17512022
TI  - Object-centred neglect: simulation with head-centred coding based on Gaussian
      gaze-dependent units.
AB  - Right brain damaged patients affected by contralesional object-centred neglect
      are able to process all objects around them but systematically omit the left part
      of these objects. We show that pure object-centred neglect can be simulated by a
      basis function neural network in which the activity of units allowing head
      centred coding of space is based on the activity of gaze-dependent units with no
      lateral gradient of preferred eye positions along the horizontal space. This type
      of network simulates complete dissociation between object-centred and egocentric
      neglect, as observed in patients' copies of multi-item drawings. Based on these
      results and available neurophysiological, clinical and brain imaging data, it is
      proposed that disruption of a cerebral network including dorsal occipital and
      parietal areas and the supplementary eye fields could be the main cause of object
      centred neglect.

PMID- 17512024
TI  - Neuroendocrine mechanisms of change in food intake during pregnancy: a potential
      role for brain oxytocin.
AB  - During pregnancy body weight, and particularly adiposity, increase, due to
      hyperphagia rather than decreased energy metabolism. These physiological
      adaptations provide the growing fetus(es) with nutrition and prepare the mother
      for the metabolically-demanding lactation period following birth. Mechanisms
      underlying the hyperphagia are still poorly understood. Although the peripheral
      signals that drive appetite and satiety centers of the brain are increased in
      pregnancy, the brain may become insensitive to their effects. For example, leptin
      secretion increases but hypothalamic resistance to leptin actions develops.
      However, several adaptations in hypothalamic neuroendocrine systems may converge
      to increase ingestive behavior. Oxytocin is one of the anorectic hypothalamic
      neuropeptides. Oxytocin neurons, both centrally-projecting parvocellular oxytocin
      neurons and central dendritic release of oxytocin from magnocellular neurons, may
      play a key role in regulating energy intake. During feeding in non-pregnant rats,
      magnocellular oxytocin neurons, especially those in the supraoptic nucleus,
      become strongly activated indicating their imminent role in meal termination.
      However, in mid-pregnancy the excitability of these neurons is reduced, central
      dendritic oxytocin release is inhibited and patterns of oxytocin receptor binding
      in the brain alter. Our recent data suggest that lack of central oxytocin action
      may partly contribute to maternal hyperphagia. However, although opioid
      inhibition is a major factor in oxytocin neuron restraint during pregnancy and
      opioids enhance food intake, an increase in opioid orexigenic actions were not
      observed. While changes in several central input pathways to oxytocin neurons are
      likely to be involved, the high level of progesterone secretion during pregnancy
      is probably the ultimate trigger for the adaptations.

PMID- 17512023
TI  - Dichotic listening after cerebral hemispherectomy: methodological and theoretical
      observations.
AB  - We examined two commonly used dichotic listening tests for measuring the degree
      of hemispheric specialization for language in individuals who had undergone
      cerebral hemispherectomy: the consonant-vowel (CV) nonsense syllables and the
      fused words (FW) tests, using the common laterality indices f and lambda.
      Hemispherectomy on either side resulted in a massive contralateral ear advantage,
      demonstrating nearly complete ipsilateral suppression of the left ear in the
      right hemispherectomy group but slightly less complete suppression of the right
      ear in the left hemispherectomy group. The results are consistent with the
      anatomical model of the ear advantage [Kimura, D. (1961). Most syllables or words
      are reported for the ear contralateral to the remaining hemisphere, while few or
      none are reported for the ear ipsilateral to the remaining hemisphere. In the
      presence of competing inputs to the two ears, the stronger contralateral ear
      hemisphere connection dominates/suppresses the weaker ipsilateral ear-hemisphere
      connection. The lambda index was similar in the two tests but the index f was
      higher in the CV than the FW test. Both indices of the CV test were sensitive to
      side of resection, higher in the right hemispherectomy than in the left
      hemispherectomy groups.

PMID- 17512026
TI  - Metabolic flux analysis in plants using dynamic labeling technique: application
      to tryptophan biosynthesis in cultured rice cells.
AB  - The concept and methodology of using dynamic labeling for the MFA of plant
      metabolic pathways are described, based on a case study to develop a method for
      the MFA of the tryptophan biosynthetic pathway in cultured rice cells. Dynamic
      labeling traces the change in the labeling level of a metabolite in a metabolic
      pathway after the application of a stable isotope-labeled compound. In this
      study, [1-(13)C] l-serine was fed as a labeling precursor and the labeling level
      of Trp was determined by using the LC-MS/MS. The value of metabolic flux is
      determined by fitting a model describing the labeling dynamics of the pathway to
      the observed labeling data. The biosynthetic flux of Trp in rice suspension
      cultured cell was determined to be 6.0+/-1.1 nmol (gFWh)(-1). It is also
      demonstrated that an approximately sixfold increase in the biosynthetic flux of
      Trp in transgenic rice cells expressing the feedback-insensitive version of
      anthranilate synthase alpha-subunit gene (OASA1D) resulted in a 45-fold increase
      in the level of Trp. In this article, the basic workflow for the experiment is
      introduced and the details of the actual experimental procedures are explained.
      Future perspectives are also discussed by referring recent advances in the
      dynamic labeling approach.

PMID- 17512025
TI  - Progesterone: its occurrence in plants and involvement in plant growth.
AB  - Progesterone is a mammalian gonadal hormone. In the current study, we identified
      and quantified progesterone in a range of higher plants by using GC-MS and
      examined its effects on the vegetative growth of plants. The growth of
      Arabidopsis (Arabidopsis thaliana) seedlings was promoted by progesterone at low
      concentrations but suppressed at higher concentrations under both light and dark
      growth conditions. The growth of the gibberellin-deficient mutant lh of pea
      (Pisum sativum) was also promoted by progesterone. An earlier study demonstrated
      that progesterone binds to MEMBRANE STEROID BINDING PROTEIN 1 (MSBP1) of
      Arabidopsis. In this work, we cloned the homologous genes of Arabidopsis, MSBP2
      and STEROID BINDING PROTEIN (SBP), as well as of rice (Oryza sativa), OsMSBP1,
      OsMSBP2 and OsSBP and examined their expression in plant tissues. All of these
      genes, except OsMSBP1, were expressed abundantly in plant tissues. The roles of
      progesterone in plant growth were also discussed.

PMID- 17512027
TI  - Oscillatory potentials of the slow-sequence multifocal ERG in primates extracted
      using the Matching Pursuit method.
AB  - This study used the Matching Pursuit (MP) method, a time-frequency analysis, to
      identify and characterize oscillatory potentials (OPs) in the primate
      electroretinogram (ERG). When the slow-sequence mfERG from the macular region of
      the retina was matched with Gabor functions, OPs were identified in two distinct
      bands: a high-frequency band peaking around 150 Hz that contributes to early OPs,
      and a low-frequency band peaking around 80 Hz that contributes to both early and
      late OPs. Pharmacological blockade and experimental glaucoma studies showed that
      the high-frequency OPs depend upon sodium-dependent spiking activity of retinal
      ganglion cells, whereas the low-frequency OPs depend primarily upon non-spiking
      activity of amacrine cells, and more distal retinal activity.

PMID- 17512029
TI  - One-dimensional modelling of the secondary clarifier-factors affecting simulation
      in the clarification zone and the assessment of the thickening flow dependence.
AB  - This paper presents a one-dimensional (1-D) model of the secondary settling tank
      (SST), and the drive for model development is discussed using steady-state
      simulation results generated with a 2-D computational fluid dynamics (CFD) model.
      Concentration profiles measured in a flat-bottom circular (fbSST) that is
      equipped with suction-lift sludge removal, served for CFD model validation. We
      investigate the factors that may deteriorate the 1-D simulation performance of
      clarifier models, which incorporate dispersion both in terms of the effluent
      sludge concentration and in terms of the sludge blanket height. Furthermore,
      dispersion-models can account for the effect of clarifier flow conditions on
      thickening performance. However, correlations, found in the literature, are shown
      to have limited efficiency under the wide flow boundary conditions examined in
      this study. Optimisation of the 1-D clarifier model structure is proposed by
      using an overflow dependent dispersion coefficient and including a feed flow
      dependent reduction factor in the downward convective velocity term. Results
      obtained show improved simulation performance in the clarification zone and allow
      for an efficient flow-dependency formulation of the thickening performance.

PMID- 17512028
TI  - Constant light rearing disrupts compensation to imposed- but not induced
      hyperopia and facilitates compensation to imposed myopia in chicks.
AB  - PURPOSE: While rearing chicks in constant light (CL) inhibits anterior segment
      growth, these conditions also induce excessive enlargement of the vitreous
      chamber. The mechanisms underlying these effects are poorly understood although
      it has been speculated that the enlarged vitreous chambers are a product of
      emmetropization, a compensatory response to the altered anterior segments. We
      examined the ability of eyes to compensate to defocusing lenses in CL as a direct
      test of their ability to emmetropize. We also studied recovery responses, i.e.
      from lens-induced changes in CL as well as CL-induced changes alone or combined
      with lens-induced changes in eyes returned to normal diurnal lighting (NL).
      METHODS: Hatchling White-Leghorn chicks were reared in either CL or NL (control)
      lighting conditions (n=36) for 2 weeks, with lenses of either +10 or -10D power
      fitted to one eye of all chicks at the beginning of the second week. The lenses
      were removed at the end of the same week, at which time some CL chicks (n=14)
      were shifted to NL, the rest of the chicks remaining in their respective original
      lighting conditions. Retinoscopy, IR photo-keratometry and high-frequency A-scan
      ultrasonography were used to track refractions, corneal radii of curvature and
      ocular axial dimensions, respectively; data were collected on experimental days
      0, 7, 9, 14 and 21. RESULTS: Under CL, eyes showed near normal, albeit slightly
      exaggerated responses to +10D lenses while the response to -10D lenses was
      disrupted. With +10D lenses, lens-wearing eyes became more hyperopic (RE), and
      had shorter vitreous chambers (VC) and optical axial lengths (OL) relative to
      their fellows by the end of the lens period [RE: +10.5+/-1.5D, CL, +8.25+/-2.5D,
      NL; VC: -0.363+/-0.129mm, CL; -0.306+/-0.110mm, NL; OL: -0.493+/-0.115mm, CL, 
      0.379+/-0.106mm, NL (mean interocular difference+/-SD)]. With -10D lenses, the NL
      group showed a myopic shift in RE and increased elongation of both VC depth and
      OL (RE: -10.75+/-2.0D; VC depth: 0.554+/-0.097mm; OL: 0.746+/-0.166mm), while the
      CL group showed a small hyperopic shift in RE (+4.0+/-6.0D). Nonetheless, CL eyes
      were able to recover from lens-induced hyperopia, whether they were left in CL or
      returned to NL. One week of exposure to NL was sufficient to reverse the effects
      of 2 weeks of CL on anterior and vitreous chamber dimensions. CONCLUSION: CL
      impairs emmetropization. Specifically, it disrupts compensation to lens-imposed
      hyperopia but not imposed myopia. However, CL eyes are able to recover from lens
      induced hyperopia, suggesting that the mechanisms underlying the compensatory
      responses to defocusing lenses are different from those involved in recovery
      responses. The ocular growth effects of CL on young eyes are reversible under NL.

PMID- 17512030
TI  - Application of quantum-chemical approximations to environmental problems:
      Prediction of physical and chemical properties of TNT and related species.
AB  - This paper presents accurate predictions of ecologically important properties of
      nitroaromatic compounds and their derivatives, including vapor pressure, Henry's
      law constants, water solubility, octanol/water partition coefficients, heats of
      formation and ionization potentials. The proposed technique of calculations was
      based on quantum-chemical methods. The relationship between the chemical
      structure and mentioned physico-chemical parameters of such widespread military
      produced contaminants as trinitrotoluene and its derivatives was considered. We
      revealed that the DFT level of theory combined with the COSMO-RS technique is
      able to predict the studied parameters with an accuracy that results in error
      bars of less then one logarithmic unit.

PMID- 17512031
TI  - Metal tolerating methylotrophic bacteria reduces nickel and cadmium toxicity and
      promotes plant growth of tomato (Lycopersicon esculentum L).
AB  - Inoculation of plants with microorganisms may reduce the toxicity of heavy metals
      to plants in contaminated soils. In this study, we have shown that the plant
      growth promoting bacteria Methylobacterium oryzae strain CBMB20 and Burkholderia
      sp. strain CBMB40 from rice reduce the toxicity of Ni and Cd in tomato and
      promote plant growth under gnotobiotic and pot culture experiments. The bacterial
      strains bound considerable amounts of Ni(II) and Cd(II) in their growing and
      resting cells and showed growth in the presence of NiCl2 and CdCl2. In
      gnotobiotic assay, inoculation with the bacterial strains reduced the ethylene
      emission and increased the tolerance index of the seedlings against different
      concentrations of NiCl2/CdCl2. In pot experiments carried out with non-polluted,
      Ni and Cd supplemented Wonjo-Mix bed soil, the results clearly demonstrated
      reduction in the accumulations of Ni(II) and Cd(II) in roots and shoots, with
      significant increase in the plant growth attributes with bacterial inoculations
      compared to untreated control. Strain CBMB20 performed better than CBMB40 in
      reducing the heavy metal accumulations in plants. Our results suggest
      conclusively, that protection against the heavy metals toxicity is rendered by
      these bacterial strains by reducing their uptake and further translocation to
      shoots in plants and promote the plant growth by other PGP characteristics.

PMID- 17512032
TI  - Probabilistic risk assessment for zinc in some commercial dishwashing detergents:
      the nitrification processes in US POTWs.
AB  - A US patent was issued to a commercial dishwashing detergent composition in which
      soluble zinc is used to protect glassware from corrosion. Some of the consumed
      detergents are discharged as wastewater and treated in publicly owned treatment
      works (POTWs). A probabilistic risk assessment was conducted to quantitatively
      determine the risk of zinc in the detergents to the nitrification processes in US
      POTWs. The procedure for POTW local limit development designed by the US
      Environmental Protection Agency (EPA) was used as a reference when conducting the
      risk assessment. The assessment took into account the background zinc
      concentrations in POTW influents and potential shock loading patterns, and was
      conducted at different market penetration rates (MPRs) for the US market of
      detergents based on the patented formula. The assessment involved several
      conservative factors including conservative determination of primary treatment
      efficiency, bioavailability, inhibition concentration, configuration of the
      nitrification process, as well as background zinc concentration in wastewater.
      With the conservative factors in the assessment, it was found that zinc in
      detergents does not present a significant risk to the nitrification processes in
      POTWs at a MPR up to 10%. It was noted that additional analyses would be required
      when the MPR is higher than 10% to adequately account for the effects of the
      conservative factors on the result of the assessment.

PMID- 17512033
TI  - Evaluation of p16INK4a, minichromosome maintenance protein 2, DNA topoisomerase
      IIalpha, ProEX C, and p16INK4a/ProEX C in cervical squamous intraepithelial
      lesions.
AB  - p16INK4a has been shown to be overexpressed in nearly all high-grade squamous
      intraepithelial lesions (HSILs). Other cell-cycle regulators, such as
      minichromosome maintenance protein 2 (MCM2), DNA topoisomerase IIalpha (TOP IIA),
      and ProE(X) C (a cocktail of MCM2 and TOP IIA), have also demonstrated some value
      in identifying squamous intraepithelial lesions. Data on direct comparison of
      those cell regulatory proteins in the detection of squamous intraepithelial
      lesions, with a focus on low-grade squamous intraepithelial lesions (LSILs), are
      limited. We immunohistochemically evaluated the diagnostic value of p16, MCM2,
      TOP IIA, ProE(X) C, and a cocktail of p16 and ProE(X) C in 62 cervical biopsy
      specimens, including 14 cases of benign squamous mucosa (group 1), 34 cases of
      LSILs (group 2), and 14 cases of HSILs (group 3). The staining intensity and
      distribution were recorded. The results demonstrated that positive staining for
      p16 and the p16/ProE(X) C was observed in 100% of cases in group 3, whereas 79%,
      86%, and 79% of cases were positive for CM2, TOP IIA, and ProE(X) C,
      respectively. ProE(X) C and the p16/ProE(X) C showed positive staining in 94% and
      100% of cases in group 2, respectively. In contrast, immunoreactivity for p16,
      MCM2, and TOP IIA was detected in only 76% of cases in group 2. Importantly, all
      8 p16-negative cases in group 2 were positive for p16/ProE(X) C (P = .003). Our
      data indicate that (1) p16 is a more sensitive and specific marker for
      identifying HSILs; (2) ProE(X) C is a better marker for the detection of LSILs;
      and (3) p16/ProE(X) C provides the highest diagnostic value for the detection of
      both HSILs and LSILs.

PMID- 17512034
TI  - Variation and diversity in Homo erectus: a 3D geometric morphometric analysis of
      the temporal bone.
AB  - Although the level of taxonomic diversity within the fossil hominin species Homo
      erectus (sensu lato) is continually debated, there have been relatively few
      studies aiming to quantify the morphology of this species. Instead, most
      researchers have relied on qualitative descriptions or the evaluation of
      nonmetric characters, which in many cases display continuous variation. Also,
      only a few studies have used quantitative data to formally test hypotheses
      regarding the taxonomic composition of the "erectus" hypodigm. Despite these
      previous analyses, however, and perhaps in part due to these varied approaches
      for assessing variation within specimens typically referred to H. erectus (sensu
      lato) and the general lack of rigorous statistical testing of how variation
      within this taxon is partitioned, there is currently little consensus regarding
      whether this group is a single species, or whether it should instead be split
      into separate temporal or geographically delimited taxa. In order to evaluate
      possible explanations for variation within H. erectus, we tested the general
      hypothesis that variation within the temporal bone morphology of H. erectus is
      consistent with that of a single species, using great apes and humans as
      comparative taxa. Eighteen three-dimensional (3D) landmarks of the temporal bone
      were digitized on a total of 520 extant and fossil hominid crania. Landmarks were
      registered by Generalized Procrustes Analysis, and Procrustes distances were
      calculated for comparisons of individuals within and between the extant taxa.
      Distances between fossil specimens and between a priori groupings of fossils were
      then compared to the distances calculated within the extant taxa to assess the
      variation within the H. erectus sample relative to that of known species,
      subspecies, and populations. Results of these analyses indicate that shape
      variation within the entire H. erectus sample is generally higher than extant
      hominid intraspecific variation, and putative H. ergaster specimens are
      significantly different from other specimens in H. erectus (sensu lato). However,
      shape distances within geographical groups of H. erectus are also high, and OH 9
      and Dmanisi 2280 are morphologically distinct from the Koobi Fora specimens that
      are sometimes classified as H. ergaster. These findings suggest that, although H.
      erectus may be composed of multiple species, the differentiation is complex, and
      specimens cannot easily be grouped geographically or chronologically.
      Consequently, more complicated scenarios seeking to explain the observed
      variation within H. erectus must be considered.

PMID- 17512035
TI  - Molar crown formation in the Late Miocene Asian hominoids, Sivapithecus parvada
      and Sivapithecus indicus.
AB  - During the past decade, studies of enamel development have provided a broad
      temporal and geographic perspective on evolutionary developmental biology in
      Miocene hominoids. Here we report some of the first data for molar crown
      development in one hominoid genus, Sivapithecus. The data are compared to a range
      of extant and extinct hominoids. Crown formation times (CFTs), daily rates of
      enamel secretion (DSR), Retzius line number and periodicity, and relative enamel
      thickness (RET) were calculated in a mandibular first molar of Sivapithecus
      parvada and a maxillary first molar of Sivapithecus indicus from the Siwalik
      sequence of Pakistan. A CFT of 2.40 years for the protoconid of S. parvada and
      2.25 years for the protocone of S. indicus lie within the range of first molar
      (M1) formation times for the majority of Miocene hominoids (1.96-2.40 years,
      excluding Proconsul heseloni), and are similar to an M(1) from Gorilla (2.31
      years) and M(1)s from Pan (2.22-2.39 years). This is unlike the longer CFTs in
      modern humans, which appear to be linked with their extended growth period. In
      contrast to extant great apes and humans, daily rates of enamel secretion are
      rapid in the Sivapithecus M1s during the early stages of growth, which seems to
      be a common pattern for most Miocene apes. The rapid accumulation of cuspal
      enamel in the Sivapithecus molars produced thicker enamel than either Pan or
      Gorilla in a comparable period of time. Future studies on larger samples of
      living and fossil hominoids are needed to clarify trends in crown development,
      which may be better understood in the context of life history strategies coupled
      with good data on body mass and brain size.

PMID- 17512036
TI  - Were neandertal and modern human cranial differences produced by natural
      selection or genetic drift?
AB  - Most evolutionary explanations for cranial differences between Neandertals and
      modern humans emphasize adaptation by natural selection. Features of the crania
      of Neandertals could be adaptations to the glacial climate of Pleistocene Europe
      or to the high mechanical strains produced by habitually using the front teeth as
      tools, while those of modern humans could be adaptations for articulate speech
      production. A few researchers have proposed non-adaptive explanations. These
      stress that isolation between Neandertal and modern human populations would have
      lead to cranial diversification by genetic drift (chance changes in the
      frequencies of alleles at genetic loci contributing to variation in cranial
      morphology). Here we use a variety of statistical tests founded on explicit
      predictions from quantitative- and population-genetic theory to show that genetic
      drift can explain cranial differences between Neandertals and modern humans.
      These tests are based on thirty-seven standard cranial measurements from a sample
      of 2524 modern humans from 30 populations and 20 Neandertal fossils. As a further
      test, we compare our results for modern human cranial measurements with those for
      a genetic dataset consisting of 377 microsatellites typed for a sample of 1056
      modern humans from 52 populations. We conclude that rather than requiring special
      adaptive accounts, Neandertal and modern human crania may simply represent two
      outcomes from a vast space of random evolutionary possibilities.

PMID- 17512037
TI  - Study of the impact of land use and hydrogeological settings on the shallow
      groundwater quality in a peri-urban area of Kampala, Uganda.
AB  - A study to assess the impacts of land use and hydrogeological characteristics on
      the shallow groundwater in one of Kampala's peri-urban areas (Bwaise III Parish)
      was undertaken for a period of 19 months. Water quality monitoring was carried
      out for 16 installed wells and one operational protected spring to ascertain the
      seasonal variation. The aspects of hydrogeological setting investigated in the
      study were the subsurface unconsolidated material characteristics (stratigraphy,
      lithology, hydraulic conductivity, porosity and chemical content), seasonal
      groundwater depths and spring discharge, topography and rainfall of the area.
      Both laboratory and field measurements were carried out to determine the soil and
      water characteristics. Field surveys were also undertaken to identify and locate
      the various land use activities that may potentially pollute. The results
      demonstrate that the water table in the area responds rapidly to short rains (48
      h) due to the pervious (10(-5)-10(-3) ms(-1)) and shallow (<1 mbgl) vadose zone,
      which consists of foreign material (due to reclamation). This anthropogenically
      influenced vadose zone has a limited contaminant attenuation capacity resulting
      in water quality deterioration following the rains. There is widespread
      contamination of the groundwater with high organic (up to 370 mgTKN/l and 779
      mgNO-3/l), thermotolerant coliforms (TTCs) and faecal streptococci (FS) (median
      values as high as 126E3 cfu/100 ml and 154E3 cfu/100 ml respectively) and total
      phosphorus (up to 13 mg/l) levels originating from multiple sources of
      contamination. These include animal rearing, solid waste dumping, pit latrine
      construction and greywater/stormwater disposal in unlined channels leading to
      increased localised microbial (faecal) and organic (TKN/NO-3) contamination
      during the rains. The spring discharge (range 1.22-1.48 m3/h) with high nitrate
      levels (median values of 117 and 129 mg/l in the wet and dry seasons) did not
      vary significantly with season (p=0.087) suggesting that this source is fed by
      regional base flow. However, the microbial quality deterioration observed in the
      spring discharge after a rain event (median values of 815TTCs cfu /100 ml and 433
      FS cfu/100 ml) was attributed to the poor maintenance of the protection
      structure. Identification and selection of appropriate management solutions for
      the protection of shallow groundwater in informal settlements should not only be
      based on water quality problems and the causal physical characteristics as
      demonstrated by this study, but also institutional and socio-economic factors.

PMID- 17512038
TI  - A single testing of serum amyloid a levels as a tool for diagnosis and treatment
      dilemmas in familial Mediterranean fever.
AB  - OBJECTIVES: In a significant proportion of patients with familial Mediterranean
      fever (FMF), serum amyloid A (SAA) remains elevated during attack-free periods,
      thereby increasing the risk of developing amyloidosis. The aim of the study was
      to determine various correlates of elevated SAA and evaluate the role of SAA
      measurement in the diagnosis and management of FMF. METHODS: We reviewed the
      medical files of all 204 patients from our FMF center in whom SAA measurements
      were performed. SAA levels and the resulting diagnostic and therapeutic decisions
      were analyzed in relation to the reasons of SAA testing and to several clinical
      and genetic parameters. RESULTS: SAA measurements were made for diagnostic
      purposes in 29% of the patients. In the remainder, SAA measurements were used for
      adjustment of colchicine dose. Elevated SAA levels are found in a third of FMF
      patients during an attack-free period. The highest rate of elevated SAA levels
      was found in patients with proteinuria (60% of this patient group), followed by
      noncompliant (40%) and genetically positive asymptomatic patients (38%). Elevated
      SAA levels during remission were associated with family history of FMF, M694V
      homozygosity, and elevated C-reactive protein (CRP) (P<0.05 for each). Patients
      homozygous for the M694V mutation had the highest level of SAA. SAA measurement
      led to a change in colchicine dose in 30% of the patients, predominantly in
      noncompliant patients and patients with proteinuria or with atypical
      manifestations. CONCLUSIONS: Measurement of SAA level may help in the diagnosis
      of FMF and in adjustment of the colchicine dose.

PMID- 17512039
TI  - All that glimmers is not gold.

PMID- 17512040
TI  - Erik von Willebrand.
AB  - In 1926, Erik von Willebrand, a Finnish physician, published the first manuscript
      describing a haemorrhagic disorder in people who were living on the Aland islands
      off the coast of Finland. This disorder is now known by the name of its
      discoverer. Since this early observation, von Willebrand disease has been
      extensively studied. Today, we know the structure and function of the von
      Willebrand factor and much of its molecular biology. With the availability of
      safe and effective products, the treatment of von Willebrand disease is
      continually improving.

PMID- 17512041
TI  - Expression of interleukin-18 in coronary plaque obtained by atherectomy from
      patients with stable and unstable angina.

PMID- 17512042
TI  - Skin test diagnosis of grass pollen allergy with a recombinant hybrid molecule.
AB  - BACKGROUND: A recombinant hybrid molecule (HM) consisting of 4 major allergens
      from timothy grass (Phl p 1, 2, 5, and 6) was expressed in Escherichia coli,
      purified, and characterized regarding its immunologic properties. OBJECTIVE: We
      sought to determine whether the recombinant HM can be used for the diagnosis of
      grass pollen allergy by means of skin testing. METHODS: Skin prick testing was
      performed in 32 patients with grass pollen allergy and in 9 control individuals
      by using increasing concentrations (4, 12, 36, and 108 mug/mL) of the HM and
      using commercial grass pollen extract. Specific IgE reactivities against the HM,
      grass pollen extract, and a panel of purified grass pollen allergens (recombinant
      Phl p 1, 2, 5, 6, 7, 12, and 13 and natural Phl p 4) were measured by means of
      ELISA, and timothy grass pollen-specific IgE levels were determined by using
      ImmunoCAP. RESULTS: Grass pollen allergy was diagnosed in all patients by means
      of skin testing with the HM. No false-positive skin test responses were obtained
      in the control individuals. There was an excellent correlation between IgE levels
      obtained with the HM and natural grass pollen extract measured by means of ELISA
      (r = 0.98, P < .0001) and by means of ImmunoCAP (r = 0.98, P < .0001).
      CONCLUSIONS: The recombinant HM permitted accurate and specific in vivo diagnosis
      of grass pollen allergy in all tested patients. It can be considered a well
      defined tool for the diagnosis and perhaps for immunotherapy of grass pollen
      allergy. CLINICAL IMPLICATIONS: A recombinant HM can replace traditional allergen
      extracts for skin test-based diagnosis of grass pollen allergy.

PMID- 17512045
TI  - Common causes of male dog infertility.
AB  - A complete breeding soundness evaluation is essential for assessment of the
      infertile male dog. Cryptorchidism, a sex-limited autosomal recessive trait, is
      more common as a unilateral condition. Azoospermia is an ejaculate consisting of
      seminal plasma but lacking sperm; repeated semen collections in the presence of
      an estrual bitch will rule out inadequate experience and lack of sexual
      stimulation. Both carnitine and alkaline phosphatase (AP) are produced in the
      epididymis; seminal plasma AP concentrations>5000 U/L indicate a normal
      ejaculate, whereas <5000 U/L is associated with incomplete ejaculation. Benign
      prostatic hypertrophy (BPH), the most common age-related condition in intact male
      dogs, is characterized by a sanguineous urethral discharge, hematuria, or
      hemospermia; diagnosis is based on prostatic enlargement and confirmed by a
      transabdominal biopsy. Although castration is recommended, valuable breeding dogs
      can be given finasteride. Prostatitis is more common in older dogs with BPH.
      Culture of the third fraction of the ejaculate or urine obtained by cystocentesis
      is indicated. Bacterial prostatitis is treated with antibiotics with high lipid
      solubility. Some dogs with bacterial prostatitis may develop prostatic abscesses
      (a medical and surgical emergency). Prostatic cysts are often asymptomatic.
      Approximately, 5-7% of dogs with prostatic disease have prostatic neoplasia, most
      commonly adenocarcinoma (it occurs in both intact and castrated dogs), which
      often metastasizes and has a very poor prognosis. Although a specific diagnosis
      can be made in many cases of male dog infertility, not all causes are amenable to
      treatment.

PMID- 17512043
TI  - Cytokine modulation of atopic dermatitis filaggrin skin expression.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is
      characterized by a defective skin barrier function. Recent studies have reported
      mutations of the skin barrier gene encoding filaggrin in a subset of patients
      with AD. OBJECTIVE: We investigated whether reduced filaggrin expression was
      found in patients with AD who were not carriers of known filaggrin mutations and
      whether filaggrin expression was modulated by the atopic inflammatory response.
      METHODS: Filaggrin expression was measured in skin biopsies and cultured
      keratinocytes using real-time RT-PCR and immunohistochemistry. Filaggrin loss-of
      function mutations were screened in a total of 69 subjects. RESULTS: Compared
      with normal skin, filaggrin expression was significantly reduced (P < .05) in
      acute AD skin, with further reduction seen in acute lesions from 3 European
      American subjects with AD who were heterozygous for the 2282del4 mutation. This
      was confirmed by using immunohistochemistry. AD skin is characterized by the
      overexpression of IL-4 and IL-13. Keratinocytes differentiated in the presence of
      IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression (0.04 +/
      0.01 ng filaggrin/ng glyceraldehyde 3-phosphate dehydrogenase; P < .05) compared
      with media alone (0.16 +/- 0.03). CONCLUSION: Patients with AD have an acquired
      defect in filaggrin expression that can be modulated by the atopic inflammatory
      response. CLINICAL IMPLICATIONS: The atopic immune response contributes to the
      skin barrier defect in AD; therefore, neutralization of IL-4 and IL-13 could
      improve skin barrier integrity.

PMID- 17512044
TI  - Global gene expression analysis during bovine oocyte in vitro maturation.
AB  - It is well known that factors such as nutrition, hormonal alterations and
      environmental compounds can have a profound effect on oocyte quality and
      subsequently embryo development. Global mRNA expression analysis of immature and
      mature bovine oocytes was carried out to identify key pathways associated with
      oocyte meiotic maturation and developmental potential. We have carried out a
      global mRNA gene expression analysis of bovine oocytes pre- and post-resumption
      of meiotic maturation using the Affymetrix GeneChip Bovine Genome Array.
      Approximately 54% of the probe sets representing 23,000 transcripts were detected
      in bovine oocytes. Of which, 821 transcripts were differentially expressed (>or=2
      fold) between the two groups (p<0.05), corresponding to 209 upregulated and 612
      down regulated transcripts in the in vitro matured oocytes compared to their
      immature counterparts. In addition, transcripts uniquely detected in germinal
      vesicle stage or metaphase II were identified. The gene expression data was
      classified according to gene ontology; in terms of biological processing, the
      majority of these genes were associated with regulation activities, including the
      regulation of: MAPK activity, translation initiation and transcription. Our
      findings are in agreement with similar data from both mouse and human oocytes.
      Taken together this data provides a molecular transcriptome blueprint of immature
      and mature mammalian oocytes. This resource will be invaluable to our long-term
      objective which is to target identified pathways to elucidate the sensitivity of
      key regulatory genes and checkpoints of oocyte maturation to internal and
      external environmental influences.

PMID- 17512046
TI  - Effect of short-term hypothyroidism on reproduction in the bitch.
AB  - Hypothyroidism in bitches has been reported to cause a variable interestrus
      interval, infertility, abortion, and stillbirth. The objective of this study was
      to evaluate the effect of experimentally induced hypothyroidism in bitches on
      fertility, pregnancy, parturition, and neonatal health. Eighteen healthy
      multiparous bitches were used; hypothyroidism was induced (by radioiodine
      administration) in nine bitches and the remaining nine served as untreated
      controls. After breeding, bitches were evaluated for pregnancy, fetal resorption,
      gestation length, litter size, duration and strength of uterine contractions
      (during parturition), interval between delivery of pups, viability of pups at
      birth, periparturient survival, and weight of pups at birth through 4 weeks of
      age. Bitches were bred a median of 19 weeks after induction of hypothyroidism.
      All bitches became pregnant and delivered term litters. There was no difference
      in the interestrus interval, litter size, or gestation length between hypothyroid
      and control bitches. Duration of uterine contractions was longer, but contraction
      strength was weaker in hypothyroid than control bitches; however, the interval
      between delivery of pups was not affected. Periparturient puppy mortality was
      significantly higher in litters from hypothyroid bitches. Viability scores and
      weight at birth were significantly lower in pups from hypothyroid bitches than
      controls. There was no difference between groups in pup weight gain during the
      first 4 weeks, in the interval from birth to the eyes opened, or to the onset of
      walking. Although hypothyroidism of relatively short duration did not affect
      fertility, it prolonged parturition and reduced pup survival in the
      periparturient period.

PMID- 17512047
TI  - Aspirin for pre-eclampsia: compelling data on benefit and risk.

PMID- 17512048
TI  - Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of
      individual patient data.
AB  - BACKGROUND: Pre-eclampsia is a major cause of mortality and morbidity during
      pregnancy and childbirth. Antiplatelet agents, especially low-dose aspirin, might
      prevent or delay pre-eclampsia, and thereby improve outcome. Our aim was to
      assess the use of antiplatelet agents for the primary prevention of pre
      eclampsia, and to explore which women are likely to benefit most. METHODS: We did
      a meta-analysis of individual patient data from 32,217 women, and their 32,819
      babies, recruited to 31 randomised trials of pre-eclampsia primary prevention.
      FINDINGS: For women assigned to receive antiplatelet agents rather than control,
      the relative risk of developing pre-eclampsia was 0.90 (95% CI 0.84-0.97), of
      delivering before 34 weeks was 0.90 (0.83-0.98), and of having a pregnancy with a
      serious adverse outcome was 0.90 (0.85-0.96). Antiplatelet agents had no
      significant effect on the risk of death of the fetus or baby, having a small for
      gestational age infant, or bleeding events for either the women or their babies.
      No particular subgroup of women was substantially more or less likely to benefit
      from antiplatelet agents than any other. INTERPRETATION: Antiplatelet agents
      during pregnancy are associated with moderate but consistent reductions in the
      relative risk of pre-eclampsia, of birth before 34 weeks' gestation, and of
      having a pregnancy with a serious adverse outcome.

PMID- 17512049
TI  - The mathematical formulation of a generalized Hooke's law for blood vessels.
AB  - It is well known that the stress-strain relationship of blood vessels is highly
      nonlinear. To linearize the relationship, the Hencky strain tensor is generalized
      to a logarithmic-exponential (log-exp) strain tensor to absorb the nonlinearity.
      A quadratic nominal strain potential is proposed to derive the second Piola
      Kirchhoff stresses by differentiating the potential with respect to the log-exp
      strains. The resulting constitutive equation is a generalized Hooke's law. Ten
      material constants are needed for the three-dimensional orthotropic model. The
      nondimensional constant used in the log-exp strain definition is interpreted as a
      nonlinearity parameter. The other nine constants are the elastic moduli with
      respect to the log-exp strains. In this paper, the proposed linear stress-strain
      relation is shown to represent the pseudoelastic Fung model very well.

PMID- 17512050
TI  - Development and characterisation of molecularly imprinted polymers based on
      methacrylic acid for selective recognition of drugs.
AB  - Specific molecularly imprinted polymers (MIPs) for the drug reserpine (RES) using
      methacrylic acid (MAA) as the functional monomer were developed and characterised
      for the first time in this study. Evaluation of the various polymers by binding
      assays indicated that the optimum ratio of functional monomer to template was
      4:1. Furthermore, the imprinting effect of the MIPs was assessed by the
      chromatographic method, which demonstrated that the MIPs had better
      chromatographic behavior and selectivity than those of the corresponding NIPs. A
      combination of BET, NMR, UV spectroscopy, and MISPE analyses for investigation of
      the imprinting and recognition properties revealed that strong specific
      interactions between the functional monomer and RES in the prepolymerization
      solutions and the aqueous solutions were probably responsible for RES
      recognition. The preparation of RES MIPs and elucidation of imprinting and
      recognition mechanisms may serve as useful references for other drug MIPs.

PMID- 17512051
TI  - Enhanced osseointegration by the chemotactic activity of plasma fibronectin for
      cellular fibronectin positive cells.
AB  - Plasma fibronectin (pFN) is known to regulate cell growth, differentiation or
      survival of osteoblasts in vitro. It is also speculated to be important for the
      early phase of osseointegration, however, its actual in vivo behavior is unknown.
      The objective of this study is to clarify the role of pFN during
      osseointegration. We developed a titanium ion-plated acrylic implant (Ti-acryl)
      for thin sectioning without removal of the implant. Either Ti-acryl or pFN-coated
      Ti-acryl (FN-Ti-acryl) was implanted in the mouse femur. Samples were taken on
      days 1-7 and on day 14 after the operation, and were decalcified and paraffin
      embedded. The bone healing process and immunofluorescence localization of pFN and
      cellular fibronectin (cFN), a marker for fibroblastic cells were examined.
      Simultaneously, the effect of pFN on chemotaxis, proliferation and
      differentiation of bone marrow stromal cells (BMSCs) was analyzed in vitro. The
      in vivo results showed that faster direct bone formation was seen for the FN-Ti
      acryl group compared to the Ti-acryl group. The in vitro results showed that pFN
      significantly promoted BMSCs chemotaxis, however, had no effect on proliferation
      or differentiation. The results indicate that pFN regulated chemotaxis of
      osteogenic cells and coating the implant with pFN enhanced earlier
      osseointegration.

PMID- 17512052
TI  - NOP receptor antagonist, JTC-801, blocks cannabinoid-evoked hypothermia in rats.
AB  - The present study used the endpoint of hypothermia to investigate cannabinoid and
      nociceptin/orphanin FQ (N/OFQ) interactions in conscious animals. Prior work has
      established that cannabinoids produce hypothermia by activating central
      cannabinoid CB(1) receptors. The administration of N/OFQ into the brain also
      causes significant hypothermia. Those data suggest a link between cannabinoid
      CB(1) receptors and N/OFQ peptide (NOP) receptors in the production of
      hypothermia. Therefore, we determined if NOP receptor activation is required for
      cannabinoid-evoked hypothermia and if cannabinoid CB(1) receptor activation is
      necessary for N/OFQ-induced hypothermia. In actual experiments, a cannabinoid
      agonist, WIN 55212-2 (2.5, 5, and 10 mg/kg, i.p.), caused significant hypothermia
      in male Sprague-Dawley rats (200-225 g). A NOP receptor antagonist, JTC-801 (1
      mg/kg, i.p.), did not affect body temperature. For combined administration, JTC
      801 (1 mg/kg, i.p.) blocked a significant proportion of the hypothermia caused by
      each dose of WIN 55212-2 (2.5, 5, and 10 mg/kg, i.p.). JTC-801 (1 mg/kg, i.p.)
      also blocked the hypothermia caused by another cannabinoid agonist, CP-55, 940 (1
      mg/kg, i.p.). In separate experiments, the direct administration of N/OFQ (9
      microg/rat, i.c.v.) into the brain produced significant hypothermia. The
      hypothermic effect of N/OFQ was blocked by JTC-801 (1 mg/kg, i.p.) but not by a
      selective cannabinoid CB(1) antagonist, SR 141716A (5 mg/kg, i.m.). The finding
      that a NOP receptor antagonist abolishes a significant percentage of cannabinoid
      induced hypothermia suggests that NOP receptor activation is required for
      cannabinoids to produce hypothermia. This interaction, quantitated in the present
      study, is the first evidence that NOP receptors mediate a cannabinoid-induced
      effect in conscious animals.

PMID- 17512053
TI  - Response to chemotherapy and tandem autologous transplantation of multiple
      myeloma patients and GSTP1 and TYMS polymorphisms.
AB  - This study examines the response to dexamethasone-doxorubicin-vincristine (DAV)
      therapy, followed by conditioning regimen and autologous stem cells
      transplantation (ASCT) in patients with multiple myeloma in relation with the
      presence of polymorphisms in genes involved in drug metabolism (GSTP1) and DNA
      synthesis (TYMS). GSTP1 G313G genotype (OR=5.49; 95% CI, 1.3-22.5, p=0.02) and
      TYMS A227A genotype (OR=3.41; 95% CI, 1.3-8.9, p=0.01) resulted significantly
      associated with a poor response following chemotherapy and the risk increased for
      the combined genotype (OR=13.54; 95% CI, 2.0-91.3, p=0.01). TYMS T157T genotype
      was significantly associated with a poor response after ASCT (OR=4.60; 95% CI,
      1.2-16.9, p=0.02). Pre-therapeutic individual determination of the GSTP1 and TYMS
      polymorphisms could help in choosing the most appropriate protocol.

PMID- 17512054
TI  - Non-target effects on aquatic decomposer organisms of imidacloprid as a systemic
      insecticide to control emerald ash borer in riparian trees.
AB  - Imidacloprid is effective against emerald ash borer when applied as a systemic
      insecticide. Following stem or soil injections to trees in riparian areas,
      imidacloprid residues could be indirectly introduced to aquatic systems via leaf
      fall or leaching. Either route of exposure may affect non-target, aquatic
      decomposer organisms. Leaves from ash trees treated with imidacloprid at two
      field rates and an intentionally-high concentration were added to aquatic
      microcosms. Leaves from trees treated at the two field rates contained
      imidacloprid concentrations of 0.8-1.3 ppm, and did not significantly affect leaf
      shredding insect survival, microbial respiration or microbial decomposition
      rates. Insect feeding rates were significantly inhibited at foliar concentrations
      of 1.3 ppm but not at 0.8 ppm. Leaves from intentionally high-dose trees
      contained concentrations of about 80 ppm, and resulted in 89-91% mortality of
      leaf-shredding insects, but no adverse effects on microbial respiration and
      decomposition rates. Imidacloprid applied directly to aquatic microcosms to
      simulate leaching from soils was at least 10 times more toxic to aquatic insects
      than the foliar concentrations, with high mortality at 0.13 ppm and significant
      feeding inhibition at 0.012 ppm.

PMID- 17512056
TI  - Comparative genomics and evolution of eukaryotic phospholipid biosynthesis.
AB  - Phospholipid biosynthetic enzymes produce diverse molecular structures and are
      often present in multiple forms encoded by different genes. This work utilizes
      comparative genomics and phylogenetics for exploring the distribution, structure
      and evolution of phospholipid biosynthetic genes and pathways in 26 eukaryotic
      genomes. Although the basic structure of the pathways was formed early in
      eukaryotic evolution, the emerging picture indicates that individual enzyme
      families followed unique evolutionary courses. For example, choline and
      ethanolamine kinases and cytidylyltransferases emerged in ancestral eukaryotes,
      whereas, multiple forms of the corresponding phosphatidyltransferases evolved
      mainly in a lineage specific manner. Furthermore, several unicellular eukaryotes
      maintain bacterial-type enzymes and reactions for the synthesis of
      phosphatidylglycerol and cardiolipin. Also, base-exchange phosphatidylserine
      synthases are widespread and ancestral enzymes. The multiplicity of phospholipid
      biosynthetic enzymes has been largely generated by gene expansion in a lineage
      specific manner. Thus, these observations suggest that phospholipid biosynthesis
      has been an actively evolving system. Finally, comparative genomic analysis
      indicates the existence of novel phosphatidyltransferases and provides a
      candidate for the uncharacterized eukaryotic phosphatidylglycerol phosphate
      phosphatase.

PMID- 17512055
TI  - Evaluation of genotoxic and non-genotoxic effects of organic air pollution using
      in vitro bioassays.
AB  - In this study, organic extracts of total suspended particles (TSP) and the
      particulate matter (PM) with the size below 2.5 microm (PM(2.5)) combined with
      organic extracts of the gas phase (GP) collected at two urban and two background
      localities were analyzed with a bacterial genotoxicity test, SOS chromotest, and
      an in vitro test for the dioxin toxicity determination, using a modified cell
      line of rat hepatoma H4IIE.luc. In addition, the samples of TSP and GP were
      analyzed for PAHs contents. The PAHs concentrations and both of the toxic
      activities at the urban localities were much higher than ones at the background
      localities. Predominantly, traffic was a source of the urban air pollution there
      which was also confirmed by the evaluation of portions of certain PAHs (BaP/BPE,
      PYR/BaP) at the localities. On the other hand, the background localities were
      apparently affected by a long-distance transport of the pollutants from urban and
      industrial centers. The results of the bioassays indicated potential health risks
      for the population exposed to the organic air pollutants, especially at the urban
      localities. Based on the collected samples, distribution of the organic
      pollutants with the toxic effects in the air was evaluated. The significant
      portion of the direct genotoxins was bound to the particles larger than 2.5
      microm. On the contrary, the indirect genotoxins were bound predominantly to the
      particles with the size below 2.5 microm. However, in the urban air they may be
      also bound to the larger particles, as well. While the direct genotoxicity may be
      related with the presence of PAH-derivatives as well as some polar organic
      pollutants, the indirect genotoxicity is related with the detected carcinogenic
      PAHs. But besides the above specified pollutants it is also necessary to consider
      the presence of other toxic components of the complex organic air pollution
      mixture that may also show potential health risks. This study demonstrates
      application of the combination of the screening bioassays for the evaluation of
      organic air pollution and identification of its health risks.

PMID- 17512057
TI  - Methodological considerations for gene expression profiling of human brain.
AB  - Gene expression profiles of postmortem brain tissue represent important resources
      for understanding neuropsychiatric illnesses. The impact(s) of quality
      covariables on the analysis and results of gene expression studies are important
      questions. This paper addressed critical variables which might affect gene
      expression in two brain regions. Four broad groups of quality indicators in gene
      expression profiling studies (clinical, tissue, RNA, and microarray quality) were
      identified. These quality control indicators were significantly correlated,
      however one quality variable did not account for the total variance in microarray
      gene expression. The data showed that agonal factors and low pH correlated with
      decreased integrity of extracted RNA in two brain regions. These three parameters
      also modulated the significance of alterations in mitochondrial-related genes.
      The average F-ratio summaries across all transcripts showed that RNA degradation
      from the AffyRNAdeg program accounted for higher variation than all other quality
      factors. Taken together, these findings confirmed prior studies, which indicated
      that quality parameters including RNA integrity, agonal factors, and pH are
      related to differences in gene expression profiles in postmortem brain.
      Individual candidate genes can be evaluated with these quality parameters in post
      hoc analysis to help strengthen the relevance to psychiatric disorders. We find
      that clinical, tissue, RNA, and microarray quality are all useful variables for
      collection and consideration in study design, analysis, and interpretation of
      gene expression results in human postmortem studies.

PMID- 17512058
TI  - Depression profile in patients with and without chronic heart failure.
AB  - OBJECTIVE: Depression often goes undetected and untreated in patients with
      chronic heart failure (CHF). To investigate whether patients with CHF show a
      specific profile of depression symptoms, we compared depression symptoms in
      depressed patients with and without CHF. METHODS: Of a total of 921 patients from
      a CHF and a psychosomatic outpatient clinic, 137 met DSM-IV diagnostic criteria
      for major depressive disorder and 113 for other depressive disorders. Depressed
      patients with CHF (n=113) and without CHF (n=137) were compared with respect to
      severity of individual DSM-IV depressive symptoms, as measured with the PHQ-9. To
      stratify for depression severity, ANCOVAs with sociodemographic characteristics
      as covariates were performed separately for patients with major depressive
      disorder and other depressive disorders. RESULTS: Among the patients meeting the
      criteria for major depressive disorder, patients with CHF reported significantly
      lower levels of depressed mood (p=.006) and worthlessness/guilt (p=.019) than
      patients without CHF. In contrast, no significant group differences were found
      for any of the other depression symptoms. Group comparisons among the patients
      with other depressive disorders completely replicated these results (p< or =.001,
      and p=.04, respectively). LIMITATIONS: Our study population of CHF patients may
      not be representative for CHF patients recruited in the general population.
      CONCLUSIONS: The diagnostic features discriminating between depressed patients
      with and without CHF are the cognitive-emotional symptoms of depression, not the
      somatic symptoms. This finding may partially explain the low recognition rate of
      depression in patients with CHF. The different profile of depression symptoms in
      patients with and without CHF should be considered in diagnosis, treatment and
      medical education.

PMID- 17512059
TI  - Quantitative analysis of ataxic gait in patients with schizophrenia: the
      influence of age and visual control.
AB  - Previous research has determined that patients with schizophrenia classically
      exhibit ataxic gait. Age and visual controls of balance are important factors,
      and may influence gait, but have not been controlled. A total of 100 patients
      with schizophrenia were included in this study, along with 50 age- and sex
      matched healthy controls. They were sampled with methods which stratified both
      groups according to age and sex. Tandem gait tests were conducted with eyes open
      and closed, and gait parameters were assessed by the footprint method. Ataxic
      gait was found to be significantly more frequent in the schizophrenic group. With
      eyes open, ataxic gait showed a significant increase with age in the
      schizophrenic group, but not in the healthy control group. Adjusting ataxic gait
      of the patients on the basis of the normal age effects measured in the healthy
      control group, the ataxic gait in the schizophrenic group increased according to
      age. Multiple logistic regression analysis revealed that old age and previous
      history of alcohol dependence/abuse were the risk factors for ataxic gait with
      eyes open. This implies that a dysfunction of the visuo-cerebellar circuit in
      patients with schizophrenia increases according to age.

PMID- 17512060
TI  - Transportation stress in young bulls alters expression of neutrophil genes
      important for the regulation of apoptosis, tissue remodeling, margination, and
      anti-bacterial function.
AB  - The transportation of beef cattle results in a stress response that is associated
      with increased susceptibility and severity of respiratory diseases, presumably
      due to an alteration in immune function. Neutrophils are phagocytic immune cells
      important in lung defense and are also targets of the stress response. The
      objective of this study was to determine if a 9h transportation of young bulls by
      road induced changes in the expression of candidate genes known to be important
      in neutrophil-mediated defense and inflammation in the lung. These neutrophil
      genes encompassed functions of apoptosis (A1 and Fas), tissue remodeling (MMP-9),
      vascular margination (L-selectin), bacterial killing (BPI), and wound healing
      (betaglycan), as well as responsiveness of the cells to stress-induced increases
      in glucocorticoid hormones (GRalpha). To explore gene expression changes, blood
      was collected, plasma harvested, and neutrophils isolated from six Belgian Blue x
      Friesian bulls (231+/-7.0 kg in weight; 282+/-4 days of age) at -24, 0, 4.5,
      9.75, 14.25, 24, and 48h relative to commencement of a 9h road transportation by
      truck. Plasma cortisol concentrations were elevated at 4.5 and 9.75h, peaking at
      50.64+/-4.46 ng/mL (P<0.0001) and confirming that the animals experienced stress.
      Blood neutrophil count was elevated between 4.5 and 14.25h (P<0.0001), reaching a
      peak that was over 3-fold higher than the -24h concentration. Neutrophil Fas gene
      expression was acutely down-regulated (P=0.02) by transportation stress, while
      expressions of MMP-9, l-selectin, and BPI were profoundly up-regulated (P=0.003,
      0.002, and <0.001 respectively). However, no changes in neutrophil expressions of
      betaglycan, GRalpha, and A1 were detected. It is concluded that a 9h
      transportation of young bulls induces a gene expression signature in blood
      neutrophils that increases their circulating numbers and may enhance their pro
      inflammatory and anti-bacterial potential.

PMID- 17512061
TI  - Rapid detection of human herpesvirus 8 DNA using loop-mediated isothermal
      amplification.
AB  - The reliability of a loop-mediated isothermal amplification (LAMP) method for the
      detection of human herpesvirus 8 (HHV-8) DNA was evaluated. Although LAMP
      products were produced with the DNA sample extracted from BCP-1 cells, LAMP
      products were not produced with the DNAs from seven other human herpesviruses.
      The detection limit of the HHV-8 LAMP method was 100 copies of target
      sequence/tube. To determine whether the HHV-8 LAMP method could be used to
      quantify viral DNA, threshold times, which are defined as the time (in s) it
      takes to reach the threshold turbidity level (0.1), were measured for the
      amplification of serial dilutions of a DNA plasmid containing the target
      sequence. The standard curve possessed a correlation coefficient of 0.9428 with a
      slope of -84.079 and y-intercept value of 1936.2. Additionally, an attempt was
      made to detect viral DNA in 17 specimens collected from Kaposi's sarcomas and two
      cell lines obtained from primary effusion lymphomas. HHV-8 DNA was detected in 14
      of the 17 Kaposi's sarcoma tissue samples and both of the primary effusion
      lymphoma cell lines. Viral DNA was not detected in HHV-8 LAMP-negative samples
      using the real-time PCR method.

PMID- 17512062
TI  - Development of a multiplex real-time PCR assay using SYBR Green 1 chemistry for
      simultaneous detection and subtyping of H9N2 influenza virus type A.
AB  - Avian influenza viruses are pathogens of economical and public health concerns.
      However, infections caused by low pathogenic avian influenza particularly H9N2
      subtype are not associated with clear clinical features. Hence, rapid detection
      and subtyping of the virus will enable immediate measures to be implemented for
      preventing widespread transmission. This study highlights the development of a
      multiplex real-time reverse-transcriptase polymerase chain reaction (RRT-PCR)
      assay using SYBR Green 1 chemistry for universal detection of avian influenza
      viruses and specific subtyping of H9N2 isolates based on melting temperatures
      (T(m)) discriminations. Three melting peaks generated simultaneously at
      temperatures 85.2+/-1.0, 81.9+/-0.9 and 78.7+/-0.9 degrees C represent NP, H9 and
      N2 gene products, respectively. The RRT-PCR assay was about 10-100-fold more
      sensitive when compared to the conventional RT-PCR method using reference H9N2
      isolate. In addition, the RRT-PCR assay was 100% sensitive as well as 92%
      specific according to the standard virus isolation method in detecting
      experimentally infected specific-pathogen-free (SPF) chickens.

PMID- 17512063
TI  - Effect of tributyltin on the development of ovary in female cuvier (Sebastiscus
      marmoratus).
AB  - Organotin compounds, such as tributyltin (TBT) used as an antifouling biocide,
      can induce masculinization in female mollusks. However, few studies addressing
      the effect of TBT in fish have been reported. This study was conducted to
      investigate effects of TBT at environmental levels (1, 10, 100ng/L) on the
      development of ovary in female cuvier. TBT exposure elevated testosterone levels,
      increased the ratio of testosterone to 17beta-estradiol and decreased 17beta
      estradiol levels in ovaries after 50 days compared to the control. Three stages
      of follicles (primary growth stage, yolk vesicle stage, vitellogenic stage) were
      observed in the ovaries of cuvier at the control and 1ng/L TBT group. The ovaries
      at the 10ng/L TBT group were characterized by the lack of vitellogenic stage
      follicles and instead had higher proportions of primary growth stage follicles.
      100ng/L TBT resulted in follicles that were entirely at the earliest (primary
      growth stage) stages of development. There was a significant increase in
      apoptotic ovarian follicular cells judged by TUNEL-positive cell at the 10ng/L
      TBT group. The TUNEL-positive follicles were observed at the 100ng/L TBT group.
      The result in the present study showed that TBT at environmentally realistic
      concentrations can inhibit the ovarian development in fish. Besides the changes
      of sex hormone induced by TBT, apoptosis appears to be one mechanism affecting
      ovarian development.

PMID- 17512064
TI  - Development and reproduction of the freshwater harpacticoid copepod Attheyella
      crassa for assessing sediment-associated toxicity.
AB  - Both freshwater and marine sediments are sinks for many anthropogenic substances.
      This may pose a risk to benthic and epibenthic organisms and it is crucial that
      toxicity tests that are available for environmental risk assessment can identify
      potentially adverse effects of sediment-associated substances on benthic
      organisms, such as harpacticoid copepods. While marine harpacticoids have been
      protected via a number of acute and chronic sediment tests, the freshwater
      harpacticoid copepod community has so far been neglected in such activities. The
      main aim of the present study was therefore to (a) find a suitable freshwater
      harpacticoid copepod, (b) establish robust laboratory mass cultures and (c)
      develop a chronic test for assessment of sediment-associated toxicity using
      spiked sediments. After several cultivation trials with a number of potential
      test species, the choice fell on the benthic freshwater harpacticoid copepod
      Attheyella crassa, a species that possesses many of the characteristic features
      identified as prerequisites for toxicity test organisms, e.g. it has a sexual
      reproduction, it is relatively easy to grow and keep in mass cultures in the
      laboratory, and it has a small body size. Owing to the relatively long generation
      time of freshwater harpacticoids (in relation to many marine harpacticoids), it
      was decided that the test should be separated into a development part (21 days)
      and a reproduction part (14 days) running in parallel. As a reference substance
      we used the fungicide tebuconazole, which is currently subject to risk assessment
      and which partitions to soil and sediment. Clear concentration-related responses
      were observed for all endpoints analyzed. Nauplia body length was the most
      sensitive endpoint with a measured time weighted LOEC(water) of 20microg/L. The
      corresponding LOEC(water) for larval mortality and offspring production was 65
      and 62microg/L, respectively. In conclusion, A. crassa is an ecologically
      relevant test species for freshwater ecosystems and particularly for the cold,
      oligotrophic and often acidic lakes of Northern Europe. Regardless of the
      relatively long generation time of this species, our results clearly show that
      sediment-associated toxicity related to development and sexual reproduction can
      be assessed within 2-3 weeks exposure with the developed bioassay.

PMID- 17512065
TI  - Quality of life (QoL) in relation to disease severity in Brazilian Parkinson's
      patients as measured using the WHOQOL-BREF.
AB  - This study aimed at evaluating and describing the QoL and its association with
      the severity of disease among Brazilian Parkinson's disease (PD) patients. In
      this cross-sectional study 68 PD patients were interviewed using the World Health
      Organization Quality of Life Instrument Short Form (WHOQOL-BREF) and the Hoehn
      Yahr (HY) scale. Analysis of variance, chi(2), Kruskal-Wallis and Mann-Whitney U
      tests, Spearman and Cronbach reliability coefficients were used to analyze the
      data. The results indicate: (1) physical capacity was the domain that showed the
      most deterioration; (2) severity of PD is associated with QoL measured by WHOQOL
      BREF; (3) overall QoL, working capacity, activities of daily living (ADL) and
      self-esteem are affected in both transitional periods in the progression of PD
      (mild to moderate and moderate to advanced). Satisfaction with general health,
      pain, energy, positive feelings, personal relationship and satisfaction with home
      are affected in the first period of transition while mobility, body image, sexual
      activity and access to information are affected in the second. This study mainly
      shows specific facets that are affected depending on the specific periods of PD
      progression, which can help to understand the impact of the disease, the
      effectiveness of care, and the demand for health care resources.

PMID- 17512066
TI  - Assessment of the health status of Greek centenarians.
AB  - The present study aims at describing the health status of a sample of relatively
      functional and healthy Greek centenarians and at exploring the potential gender
      differences in health in this sample. Its objectives are to add to the
      accumulation of knowledge about the health status of centenarians and therefore
      to contribute to the exploration of the mechanisms of healthy longevity. The
      study employs a non-representative community sample of Greek centenarians of both
      sexes (N=47). It uses descriptive statistics in order to outline the health
      status of the participants and non-parametric tests to assess the statistical
      significance of the observed sex-differences. The study shows that the
      centenarians of our sample are relatively healthy and functional (15% of the
      sample was free of any major chronic disease). It also suggests, that the sex
      difference in survival is statistical significant (p< or =0.013), and that the
      morbidity and co-morbidity rates of the Greek centenarians are relatively low
      (mean value of co-morbidity=1.4+/-0.97, S.D.). Moreover, it provides valuable
      information on the anthropometric characteristics of the sample, and on health
      services utilization. These results indicate that exceptional longevity is not
      necessarily accompanied by disability, disease and total dependence on others.

PMID- 17512067
TI  - Evaluation of fungal aerosols using Temporal Temperature Gradient Electrophoresis
      (TTGE) and comparison with culture.
AB  - Information obtained from fungal air samples can assist in the assessment of
      health hazards and can be useful in proactive indoor air quality monitoring. The
      objective of the present study was to evaluate the PCR-TTGE technique for the
      analysis of fungal diversity in the air. Eleven air samples were collected in
      five different sites using the bioimpactor CIP 10-M (Arelco). After a 2 hours
      sampling period, the collection liquid was recovered for subsequent cultivation
      and PCR-TTGE. A set of three fungi-specific primers (Fungcont 1, Fungcont 2+GC
      and Fungcont 3) was designed for the partial amplification of the 18S rRNA gene.
      The amplification was obtained in a single reaction tube by a semi-nested PCR.
      For identification, the TTGE bands were extracted and sequenced. PCR-TTGE allowed
      the clear separation of amplicons corresponding to distinct fungal species (both
      Ascomycota and Basidiomycota) that may be encountered in air. The number of
      fungal taxa detected after culture was systematically higher than the number of
      taxa found using PCR-TTGE. However, few fungal species were detected by PCR-TTGE
      and not by cultivation, suggesting that the combination of these approaches may
      provide a better analysis of fungal diversity in air samples than either method
      alone.

PMID- 17512068
TI  - Biomimetic engineering of cellulose-based materials.
AB  - Biomimetics is a field of science that investigates biological structures and
      processes for their use as models for the development of artificial systems.
      Biomimetic approaches have considerable potential in the development of new high
      performance materials with low environmental impact. The cell walls of different
      plant species represent complex and highly sophisticated composite materials that
      can provide inspiration on how to design and fabricate lightweight materials with
      unique properties. Such materials can provide environmentally compatible
      solutions in advanced packaging, electronic devices, vehicles and sports
      equipment. This review gives an overview of the structures and interactions in
      natural plant cell walls and describes the first attempts towards mimicking them
      to develop novel biomaterials.

PMID- 17512070
TI  - DNA damage-induced signalling in ataxia-telangiectasia and related syndromes.
AB  - ATM, the protein mutated in the human genetic disorder ataxia-telangiectasia,
      functions by responding to radiation damage to DNA, primarily DNA double strand
      breaks (dsb), to reduce the risk of genome instability, cancer and
      neurodegeneration. ATM is rapidly activated as an existing protein to
      phosphorylate a number of downstream proteins that are involved in DNA repair and
      cell cycle checkpoint activation. While the exact mechanism of activation of ATM
      has not been determined, it is now evident that it relies heavily on the Mre11
      complex (Mre11/Rad50/Nbs1) and a series of post-translational events for this
      activation. The Mre11 complex acts as a sensor for the break, recruits ATM to
      this site where it is autophosphorylated and then is capable of phosphorylating
      substrates that participate in DNA repair and cell cycle control. A greater
      understanding of how ATM is activated and functions through different signalling
      pathways is paramount to devising therapeutic strategies for the treatment of A-T
      patients. This knowledge can also be used to advantage in sensitizing cells to
      radiation and ultimately deriving novel therapeutic approaches for the treatment
      of cancer.

PMID- 17512071
TI  - Expression of EGFR variant vIII promotes both radiation resistance and hypoxia
      tolerance.
AB  - BACKGROUND AND PURPOSE: EGFRvIII has been described to function as an oncoprotein
      with constitutive activation promoting neoplastic transformation and
      tumorigenicity. The present study was undertaken to test whether EGFRvIII also
      contributes to hypoxia tolerance. MATERIAL AND METHODS: The human glioma cell
      line U373 was genetically modified to stably express EGFRvIII. Western blotting
      and immunohistochemistry verified the expression of EGFRvIII. Tumour xenografts
      were produced by injecting U373 control and EGFRvIII positive cells
      subcutaneously into the lateral flank of recipient mice. Colony formation assays
      were performed after ionizing radiation at 4Gy and after exposure to anoxia for 1
      4 days. RESULTS: EGFRvIII accelerated tumour growth leading to a 3.5-fold
      increase in tumour size compared to control tumours at 40 days after cell
      injection. EGFRvIII promoted clonogenic survival by almost 2-fold and 4-fold
      after 4Gy and 4 days of anoxia, respectively. EGFRvIII was also associated with a
      substantially bigger colony size after anoxic treatment. CONCLUSIONS: EGFRvIII
      expression stimulates the growth of tumour xenografts and strongly promotes
      survival after irradiation and under hypoxic stress.

PMID- 17512072
TI  - Differential gene expression before and after ionizing radiation of subcutaneous
      fibroblasts identifies breast cancer patients resistant to radiation-induced
      fibrosis.
AB  - BACKGROUND AND PURPOSE: Differentially gene expression between patients with
      either very low or very high risk of radiation-induced fibrosis (RIF) in patient
      derived fibroblasts after irradiation has previously been reported. In the
      present study, we are investigating the robustness of radiation-induced changes
      in gene expression in fibroblasts, whether differential expression is more
      pronounced when looking at the fold induction levels, taking into account the
      differences in background expression levels between patients, and whether there
      is a linear correlation between individual risk of RIF and changes in radiation
      induced gene expression in fibroblasts. MATERIAL AND METHODS: Gene expression was
      analysed by quantitative real-time PCR before and after a fractionated scheme
      with 3x3.5Gy/3 days in fibroblasts derived from 26 patients with breast cancer
      treated with post-mastectomy radiotherapy. RESULTS: Robust radiation-induced
      changes in gene expression were observed, with differential gene expression
      between low and high risk patients being most pronounced for the fold induction
      level ('after' value divided by 'before' value for each patient). When including
      patients with intermediate risk, there was no linear correlation between
      individual risk of RIF and differential expression of the genes investigated.
      Rather, differential gene expression could divide patients into two clearly
      separated groups, a larger, sensitive group and a smaller resistant group.
      CONCLUSIONS: Differential gene expression in irradiated fibroblasts might be an
      important tool in the identification of differences in the genetic background
      between patients with variable risk of RIF, and in the identification of new
      targets for prevention and intervention of the fibrotic process.

PMID- 17512073
TI  - Transcriptional response to ionizing radiation in human radiation sensitive cell
      lines.
AB  - BACKGROUND AND PURPOSE: Radiation is a common treatment of cancer, but some
      patients show severe side effects when exposed to small doses of radiation. The
      aim of this study was to explore the underlying cause of radiation sensitivity in
      a group of radiation sensitive patients. MATERIALS AND METHODS: Lymphoblastoid
      cell lines from 5 normal individuals, 4 Ataxia Telangiectasia (AT), and 12 non-AT
      radiation sensitive (RS) patients were irradiated. RNA was isolated before and
      after radiation and hybridized to 15k cDNA microarrays and gene expression was
      recorded. RESULTS AND CONCLUSION: The RS cell lines showed an expression
      phenotype different from both the AT and normal cell lines. Six of the RS cell
      lines had a distinct expression profile before radiation. This implies that the
      RS patients are a heterogeneous group, but that six of the patients may have a
      common cause of radiation sensitivity.

PMID- 17512074
TI  - A microarray for monitoring the production of mycotoxins in food.
AB  - A microarray, which covers most of the known relevant mycotoxin biosynthesis
      genes, has been developed. The microarray carries oligonucleotides of the
      fumonisin, the aflatoxin, the ochratoxin, the trichothecene (type A and B) and
      the patulin biosynthesis pathways. For trichothecene producing Fusaria the
      biosynthesis cluster of trichothecene producing Fusarium sporotrichioides (type
      A) and of Gibberrella zeae (type B, teleomorph of F. graminearum) have been
      spotted. The aflatoxin cluster carries oligonucleotides specific for Aspergillus
      flavus. The ochratoxin pattern is specific for ochratoxin A producing Penicillia,
      the fumonisin cluster is specific for G. moniliformis (teleomorph of F.
      verticillioides) and the patulin genes have been obtained from Penicillium
      expansum. The microarray is designed in a way that newly identified pathway genes
      can be added easily at any time. The microarray was used to detect the activation
      of all gene clusters under conditions conducive for mycotoxin biosynthesis.
      According to the results the obtained signals were specific under the
      hybridization conditions used and only insignificant cross-hybridizations
      occurred. The microarray was used to demonstrate differences in mycotoxin pathway
      gene expressions after growth on various media for trichothecene and ochratoxin A
      biosynthesis. It was used further to study and compare the expression kinetics of
      the trichothecene biosynthesis genes of Fusarium on different trichothecene
      supporting media. An expression pattern indicative for trichothecene biosynthesis
      could be identified.

PMID- 17512075
TI  - Arabidopsis thaliana is a host of the legume nanovirus Faba bean necrotic yellows
      virus.
AB  - We report infection of Arabidopsis thaliana with the legume nanovirus Faba bean
      necrotic yellows virus (FBNYV) by its insect vector Aphis craccivora. Symptoms of
      FBNYV infection on A. thaliana include stunting and reduced apical dominance, and
      are rather mild, compared to the severe necrosis and early plant death induced by
      the virus in the natural host Vicia faba. An inoculation access period of 6h is
      sufficient to transmit FBNYV to A. thaliana. FBNYV is readily transmitted back
      from A. thaliana to V. faba, where it induces the characteristic severe disease
      symptoms. Hence, passage through A. thaliana does not affect FBNYV pathogenicity.
      FBNYV accumulates to the highest levels in roots and stems, compared to cauline
      and rosette leaves. In cauline leaves, the kinetics of virus accumulation
      correlates with the amount of master Rep protein accumulation.

PMID- 17512076
TI  - Influence of fillers in powder formulations containing N-acetyl-L-cysteine on
      nasal peptide absorption.
AB  - We examined the influence of filler species on the nasal absorbability of peptide
      drugs via a newly developed powdery formulation system containing N-acetyl-l
      cysteine (NAC) as an absorption enhancer. Using salmon calcitonin (SCT) as the
      principal model drug, we tested the effects of various formulations with
      different powder materials as fillers on the nasal absorption of SCT in rats. An
      intranasal administration experiment revealed that the use of less wettable
      powders provided better nasal absorbability, and the highest absolute
      bioavailability (30.0% +/- 8.6%) was obtained when ethylcellulose was used as a
      filler. All these results were readily explicable in terms of our hypothetical
      enhancing mechanism. Furthermore, human parathyroid hormone and insulin were
      applied to this ethylcellulose formulation system, giving nasal bioavailabilities
      of 28.2% +/- 6.5% and 23.4% +/- 10.6%, respectively, thus suggesting that this
      formulation system is widely applicable to peptide drugs.

PMID- 17512077
TI  - Fabrication and characterization of PLGA/HAp composite scaffolds for delivery of
      BMP-2 plasmid DNA.
AB  - The objective of this study is to construct complex of DNA and PLGA/HAp composite
      scaffold for bone tissue engineering. Naked DNA has low transfection efficiency
      so DNA loaded chitosan particles are used nowadays in gene delivery due to their
      high transfection efficiency, but unfortunately this is accompanied by strong
      immunological reaction of cells. In order to preserve the advantage of polymeric
      particles and reduce immunological effect at the same time, a new DNA release
      system is developed which makes possible sustained DNA release with negligible
      immunological effects. Poly (lactide-co-glycolide) (PLGA)/Hydroxylapatite (HAp)
      composite scaffolds with different HAp contents (0%, 5% and 10%) are fabricated
      by an electrospinning method and DNA is incorporated into the scaffolds in 3 ways
      (i.e. naked DNA, encapsulation of DNA/chitosan nanoparticles into scaffolds after
      fiber fabrication by dripping, and encapsulation of DNA/chitosan nanoparticles
      into scaffold by mixing with PLGA/HAp solution before fiber fabrication). All the
      scaffolds are characterized by SEM, XRD, DSC and GC-MS and the results show that
      the scaffolds are non-woven, nano- to micro-fibered membrane structures composed
      predominantly of PLGA with amorphous dispersion of HAp nanoparticles inside
      polymeric matrix. In vitro release tests were carried out on 9 different
      scaffolds to check the effects of HAp contents and the encapsulation ways of DNA
      on the release properties. These effects are also tested by human marrow stem
      cells (hMSCs) by comparing their cell attachment ability, cell viability and DNA
      transfection efficiency. It is demonstrated that the addition of HAp
      nanoparticles increased the release rate of DNA for both naked and encapsulated
      DNA. Cell culture experiments show that the scaffolds with encapsulated
      DNA/chitosan nanoparticles have higher cell attachment, higher cell viablility
      and desirable transfection efficiency of DNA. The observations show that
      DNA/chitosan nanoparticles encapsulated PLGA/HAp composite scaffold is promising
      for use in bone regeneration.

PMID- 17512079
TI  - Functional restoration programs for low back pain: a systematic review.
AB  - BACKGROUND: In developed countries, chronic low back pain (LBP) is one the most
      common reasons for disability and work-time loss. Conventional treatments have
      not slowed the increasing prevalence of chronic LBP. Therefore, in a search for
      new solutions to the problem, functional restoration programs were developed.
      OBJECTIVE: To synthesize the literature on the efficacy of functional restoration
      programs for LBP. METHODS: We performed a systematic literature search of the
      MedLINE database using the keywords LBP, functional restoration, work-hardening
      program, exercise therapy, rehabilitation, aerobic, and cognitive behavioral
      therapy. SYNTHESIS: The term "functional restoration" has been associated with a
      full-day multidisciplinary program lasting from 3 to 6 weeks. Results of most
      published controlled studies on the efficacy of functional restoration programs
      are positive regarding the return-to-work rate. Maintaining job status with the
      pre-injury employer is often best accomplished by the provision of suitable
      modified duties. Finally, results of functional restoration programs in terms of
      return-to-work rate probably depend strongly on the social security system of the
      country where the program was developed.

PMID- 17512078
TI  - Blood-brain barrier delivery of protein and non-viral gene therapeutics with
      molecular Trojan horses.
AB  - The products of biotechnology, recombinant proteins, monoclonal antibodies,
      antisense, RNA interference, or non-viral gene transfer, cannot be developed as
      pharmaceuticals for the brain, unless these molecules are re-formulated to enable
      transport across the blood-brain barrier (BBB). Large molecule drugs, and plasmid
      DNA, can be delivered across the BBB with receptor-specific molecular Trojan
      horses. Trojan horse BBB delivery systems, coupled with one of 3 different
      technology platforms (fusion proteins, avidin-biotin, or Trojan horse liposomes),
      can enable the BBB transport of virtually any large molecule drug or plasmid DNA.

PMID- 17512081
TI  - [Pain in adults with cerebral palsy].
AB  - INTRODUCTION: Pain is the main problem in patients with cerebral palsy. To
      improve the quality of life of people with cerebral palsy, a good knowledge of
      the clinical syndrome is necessary. METHOD: We reviewed the published data of the
      APIB study. We analysed data about pain, especially its correlation with age,
      motor handicap, and depressive syndrome. We also reviewed the literature to
      survey the pain syndrome in such a situation. RESULTS: A total of 562 patients
      responded to the APIB survey (mean age 36+/-14 years). Of these, 75% complained
      about physical pain. Pain was significantly associated with age, motor handicap,
      depressive syndrome, and sleep disorders. DISCUSSION: A study of the literature
      confirms our results on pain in cerebral palsy from the APIB survey. The main
      localisations of pain are the spine, and scapular and pelvic girdles. Pain
      syndromes of the upper and lower limbs are also frequent, with much due to
      overuse. Some rare causes include heterotopic ossifications. CONCLUSION: A good
      knowledge of the characteristics of the pain syndromes in people with cerebral
      palsy is important because of the great prevalence of this problem in this
      population. Better knowledge will help prevent the pain and improve quality of
      life.

PMID- 17512082
TI  - Cross-sectional association between BMI, glycemic control and energy intake in
      Japanese patients with type 2 diabetes. Analysis from the Japan Diabetes
      Complications Study.
AB  - Although, weight loss is associated with improved glycemic control in diabetic
      patients, the relationships between patient weight, daily energy intake (EI), and
      glycemic or other control status have been poorly investigated. Baseline
      characteristics of the Japan Diabetes Complications Study, a representative
      cohort of Japanese diabetic patients, were used for quartile analysis stratified
      according to patient body mass index (BMI) and EI. Despite a 1.4-fold discrepancy
      in BMI between the highest and the lowest quartiles, no significant linear trend
      in HbA(1C) levels or EI between quartiles was seen, although, waist/hip ratio,
      blood pressure, total cholesterol and triglycerides increased and HDL cholesterol
      decreased with the increase in BMI. Quartile analysis, according to EI, revealed
      a 1.8-fold elevation in EI between the lowest and the highest quartile.
      Nevertheless, the differences in patient BMI between the lowest and the highest
      quartile were no more than 3% and there were no significant linear trends among
      the four quartiles in most parameters including HbA(1C), blood pressure, serum
      lipids. These results revealed only very limited cross-sectional correlations
      among BMI, EI and other parameters suggesting that it is necessary to consider
      much wider variations in ideal weight and optimal dietary prescription when
      making assessments of diabetic patients.

PMID- 17512083
TI  - Functional association of the morphogenic factors with the clusterin for the
      pancreatic beta-cell differentiation.
AB  - Several differentiation or morphogenic factors have known to be involved in the
      developmental process of endocrine pancreas. However, mechanism of action and
      functional relation of these molecules are not well elucidated particularly in
      beta-cell formation from adult pancreatic stem cells. We hypothesized that adult
      pancreatic stem cells could be activated by the functional resumption of the
      morphogenic factors that were involved in embryonic development of pancreas in
      the duct system under the specific conditions such as tissue injuries. Besides
      the well-established genes including Pdx-1 and Ngn-3, we propose the nestin and
      clusterin as the new morphogenic factors for beta-cell neogenesis and their
      functional associations. We found extensive in vivo formation of ductules showing
      a higher replicating ability following the experimental tissue injury. These
      neogenic ductules were lined with low epithelial cells positive for the nestin,
      which has been known as neuronal stem cell marker. In in vitro culture, the
      nestin-rich epithelial cells of the neogenic ductules also displayed extensive
      self-replication leading to monolayer of epithelial cell explants and transformed
      into the insulin secreting beta cells as well as duct cells. Thus, we depicted
      them as nestin-positive duct stem (NPDS) cells. We found a neogenesis specific
      protein 'clusterin' in the regenerating pancreatic tissues with concomitant
      increase of Pdx-1 and Ngn-3 expression. The protein is expressed predominantly in
      the neogenic pancreas undergoing differentiation. In vitro over-expression of the
      clusterin gene strongly induces beta-cell transformation from neogenic ductal
      cells. Insulin expression, both insulin mRNA and peptide levels, was increased
      and showed glucose dependent manner by ectopic expression of clusterin upon the
      culture of neogenic ductules when compared to the mock-transfected control,
      implying that the duct cells transformed functional beta cells. We observed that
      clusterin over-expression led to up-regulation of Pdx-1 and Ngn-3, and clusterin
      levels were increased upon the transfection of cDNAs of Pdx-1 or Ngn-3,
      suggesting a close functional association of these morphogenic factors. In
      conclusion, we suggest that adult pancreatic stem cells can be recapitulated for
      neogenesis of insulin secreting beta cells not only by reactivation Pdx-1 and Ngn
      3, the classical differentiation factors for pancreas development, but also by
      the intervention of new morphogenic factors including nestin and clusterin. In
      particular, by modulation of Pdx-1 and Ngn-3, clusterin induces remarkable
      differentiation of the functional beta cells secreting insulin in response to
      glucose stimulation.

PMID- 17512085
TI  - Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and
      consequences.
AB  - Hepatic insulin resistance is an important underlying cause of the metabolic
      syndrome that manifests itself in diseases such as diabetes type II,
      atherosclerosis or non-alcoholic fatty liver disease (NAFLD). In this paper, we
      summarize comprehensively the current state of knowledge pertaining to the
      molecular mechanisms that lead to insulin resistance in hepatocytes and
      sinusoidal liver cells. In hepatocytes, the insulin resistant state is brought
      about by at least one, but more likely by a combination, of the following
      pathological alterations: hyperglycaemia and hyperinsulinaemia, formation of
      advanced glycation end-products, increased free fatty acids and their
      metabolites, oxidative stress and altered profiles of adipocytokines. Insulin
      resistance in hepatocytes distorts directly glucose metabolism, especially the
      control over glucose output into the circulation and interferes with cell
      survival and proliferation, while hepatic fatty acid synthesis remains stimulated
      by compensatory hyperinsulinaemia, resulting in steatosis. Very few studies have
      addressed insulin resistance in sinusoidal liver cells. These cells are not
      simply bystanders and passive witnesses of the changes affecting the hepatocytes.
      They are target cells that will respond to the pathological alterations occurring
      in the insulin resistant state. They are also effector cells that may exacerbate
      insulin resistance in hepatocytes by increasing oxidative stress and by secreting
      cytokines such as TNF and IL-6. Moreover, activation of sinusoidal endothelial
      cells, Kupffer cells and stellate cells will lead to chemo-attraction of
      inflammatory cells. Finally, activation of stellate cells will set in motion a
      fibrogenic response that paves the way to cirrhosis.

PMID- 17512084
TI  - Modulation of MAPK pathways and cell cycle by replicating hepatitis B virus:
      factors contributing to hepatocarcinogenesis.
AB  - BACKGROUND/AIMS: Chronic infection with the hepatitis B virus (HBV) is strongly
      associated with the development of hepatocellular carcinoma but the mechanism by
      which this occurs is unknown. Numerous studies have focused on the HBV X protein
      showing that it activates signal transduction pathways while few have
      investigated these changes in HBV-replicating hepatocytes. METHODS: We utilized
      the recombinant adenovirus system to deliver a replication competent HBV genome
      into Huh7 and primary marmoset hepatocytes (PMH) to examine the effects of active
      viral replication on the regulation of Ras-ERK signal transduction and related
      pathways. RESULTS: Huh7 cells and PMHs replicating HBV demonstrated significant
      upregulation in phosphorylated ERK, Akt, c-myc together with increased p53,
      cyclin B1 and p21(cip1) expression and cell cycle progression to G2 phase in the
      absence of increased cell proliferation. Phosphorylation of the key cell survival
      kinase, Akt, was significantly increased, resulting in increased serine
      phosphorylation of the downstream target, GSK3-beta. CONCLUSIONS: These results
      demonstrated simultaneous activation of the MAP Kinase and Akt pathways in HBV
      replicating hepatocytes that resulted in dysregulation in the control of cell
      cycle progression and which help explain the early pathogenic mechanisms that
      underlie malignant transformation associated with chronic hepatitis B infection.

PMID- 17512086
TI  - Managing to manage healthcare resources in the English NHS? What can health
      economics teach? What can health economics learn?
AB  - OBJECTIVES: To provide a 'thick description' of how decision-makers understand
      and manage healthcare prioritisation decisions, and to explore the potential for
      using economic frameworks in the context of the NHS in England. METHODS:
      Interviews were conducted with 22 key decision-makers from six Primary Care
      Trusts (PCTs) in northern England. A constant comparative approach was used to
      identify broad themes and sub-themes. RESULTS: Six broad themes emerged from the
      analysis. In summary, decision-makers recognised the concepts of resources
      scarcity, competing claims, and the need for choices and trade-offs to be made.
      Decision-makers even went on to identify a common set of principles that ought to
      guide commissioning decisions. However, the process of commissioning was
      dominated by political, historical and clinical methods of commissioning which,
      failed to recognise these concepts in practice, and departed from the principles.
      As a result, the commissioning process was viewed as not being systematic or
      transparent and, therefore, seen as underperforming. CONCLUSIONS: Health
      economists need to acknowledge the importance of contextual factors and the
      realities of priority setting. Our research suggests that the emphasis should be
      on integrating principles of economics into a management process rather than
      expecting decision-makers to apply the output of ever more seemingly 'technically
      sound' health economic methods which cannot reflect the dominating and driving
      complexities of the commissioning process.

PMID- 17512087
TI  - Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied
      3 days per week in one or two courses of treatment for actinic keratoses on the
      head.
AB  - BACKGROUND: A shorter dosing regimen of imiquimod for the treatment of actinic
      keratosis may be effective, with long-term clinical benefits. OBJECTIVE:
      Imiquimod in one or two shorter courses of treatment was evaluated. METHODS:
      Patients with actinic keratosis lesions on the head applied imiquimod or vehicle
      cream 3x/wk for 4 weeks (course 1). Patients with remaining lesions received
      another course of treatment. Complete and partial clearance rates were evaluated
      after course 1, after course 2 (overall), and 1 year later. RESULTS: Complete
      clearance rates were 26.8% (course 1) and 53.7% (overall). Partial clearance
      rates were 36.6% (course 1) and 61.0% (overall). One-year follow-up recurrence
      rates were 39% (imiquimod) and 57% (vehicle). LIMITATIONS: Blinded investigators
      may have been biased toward patients treated with imiquimod identified by
      treatment site reactions. CONCLUSION: Imiquimod 3x/wk in one or two courses of
      treatment appears to be effective for the treatment of actinic keratoses on the
      head, providing long-term clinical benefits. Some recurrences do occur, so long
      term follow-up is recommended.

PMID- 17512088
TI  - Classifying foods in contexts: how adults categorize foods for different eating
      settings.
AB  - This project examined adults' food cognitions by applying schema theory to
      explain how adults categorized foods for different contexts. Qualitative
      interviews and repeated card sort activities for different eating contexts were
      conducted to elicit as many food categories as possible from 42 US adults.
      Participants labeled card sort piles with their own words, providing 991 card
      sort labels. Qualitative analysis of the labels resulted in the emergence of 12
      category types. Personal-experience-based types were specific to the individual
      (e.g., Preference). Context-based types were related to situational aspects of
      eating episodes (e.g., Location). Food-based types were related to intrinsic
      properties of the foods (e.g., Physical characteristics). Different combinations
      of the 12 category types were used for different eating contexts. Personal
      experience and context-based types were used most frequently overall. Some
      category types were used more frequently for specific contexts (e.g., Convenience
      for work contexts). Food-based taxonomic category types were used most frequently
      when no context was defined. Script-oriented categories were more often used in
      response to specific eating contexts. These findings provide a framework to
      consider how individuals classify foods in real-life eating contexts. Attention
      to personal-experience and context-based category types may help improve
      understanding of relationships between knowledge and food choice behaviors.

PMID- 17512089
TI  - Perceived parental control of food intake is related to external, restrained and
      emotional eating in 7-12-year-old boys and girls.
AB  - This study examined the prevalence of external, restrained and emotional eating
      and the relationship of these disturbed types of eating behaviours with perceived
      parental control of food intake (pressure to eat and restriction) in a group of 7
      to 12-year-old boys and girls (n = 596). External eating turned out to be the
      most prevalent disturbed eating behaviour for boys and girls, followed by
      restrained eating and emotional eating. Sex differences were found in external
      and restrained eating. For the boys, perceived pressure to eat was positively
      related to emotional and external eating. For both sexes, perceived restriction
      to eat was negatively related to emotional and external eating and positively
      related to restrained eating. This led to the conclusion that perceived pressure
      to eat has a disruptive effect on a child's self-regulating mechanism of food
      intake, particularly so for boys, whereas perceived restriction can also have a
      positive effect.

PMID- 17512090
TI  - Antiepileptic effects of ghrelin on pentylenetetrazole-induced seizures in rats.
AB  - It is well known that neuropeptide Y (NPY) and gamma-aminobutyric acid (GABA)
      exert antiepileptic effects in animal models. It has recently been shown that
      ghrelin neurons increase the activities of GABA and NPY in the brain. Therefore
      it can be said that ghrelin is an antiepileptic agent. In this study we aimed to
      investigate the antiepileptic effect of ghrelin in an acute experimental epilepsy
      model in pentylenetetrazole (PTZ) injected rats. Adult male Wistar albino rats
      were divided into a control group and four experimental groups with seven rats in
      each group. In order to generate epileptic seizures, PTZ (50mg/kg) was injected
      intraperitoneally. The experimental groups received intraperitoneal injections of
      ghrelin at doses of 20, 40, 60 and 80microg/kg 30min before PTZ injection. After
      PTZ injection, the latencies were separated into three components: first
      myoclonic jerk, generalized clonic seizures and tonic generalized extension. The
      injection of 50mg/kg PTZ-induced epileptic seizures in the control group. The
      onset times of the three characteristic behavioral changes were significantly
      delayed and the duration of tonic generalized extension was diminished by dose
      dependent ghrelin administration. Our results demonstrated that ghrelin
      suppresses the onset time of PTZ-induced seizures. In the light of our current
      knowledge, it seems that ghrelin may be considered as an antiepileptic drug.

PMID- 17512091
TI  - Downregulation of glutaredoxin but not glutathione loss leads to mitochondrial
      dysfunction in female mice CNS: implications in excitotoxicity.
AB  - Oxidative stress, excitotoxicity and mitochondrial dysfunction play synergistic
      roles in neurodegeneration. Maintenance of thiol homeostasis is important for
      normal mitochondrial function and dysregulation of protein thiol homeostasis by
      oxidative stress leads to mitochondrial dysfunction and neurodegeneration. We
      examined the critical roles played by the antioxidant, non-protein thiol,
      glutathione and related enzyme, glutaredoxin in maintaining mitochondrial
      function during excitotoxicity caused by beta-N-oxalyl amino-L-alanine (L-BOAA),
      the causative factor of neurolathyrism, a motor neuron disease involving the
      pyramidal system. L-BOAA causes loss of GSH and inhibition of mitochondrial
      complex I in lumbosacral cord of male mice through oxidation of thiol groups,
      while female mice are resistant. Reducing GSH levels in female mice CNS by
      pretreatment with diethyl maleate or L-propargyl glycine did not result in
      inhibition of complex I activity, unlike male mice. Further, treatment of female
      mice depleted of GSH with L-BOAA did not induce inhibition of complex I
      indicating that GSH levels were not critical for maintaining complex I activity
      in female mice unlike their male counterpart. Glutaredoxin, a thiol disulfide
      oxidoreductase helps maintain redox status of proteins and downregulation of
      glutaredoxin results in loss of mitochondrial complex I activity. Female mice
      express higher levels of glutaredoxin in certain CNS regions and downregulation
      of glutaredoxin using antisense oligonucleotides sensitizes them to L-BOAA
      toxicity seen as mitochondrial complex I loss. Ovariectomy downregulates
      glutaredoxin and renders female mice vulnerable to L-BOAA toxicity as evidenced
      by activation of AP1, loss of GSH and complex I activity indicating the important
      role of glutaredoxin in neuroprotection. Estrogen protects against mitochondrial
      dysfunction caused by excitotoxicity by maintaining cellular redox status through
      higher constitutive expression of glutaredoxin in the CNS. Therapeutic
      interventions designed to upregulate glutaredoxin may offer neuroprotection
      against excitotoxicity in motor neurons.

PMID- 17512093
TI  - Transthyretin: a key gene involved in the maintenance of memory capacities during
      aging.
AB  - Aging is often associated with decline of memory function. Aged animals, like
      humans, can naturally develop memory impairments and thus represent a useful
      model to investigate genes involved in long-term memory formation that are
      differentially expressed between aged memory-impaired (AI) and aged memory
      unimpaired (AU) animals following stimulation in a spatial memory task. We found
      that alterations in hippocampal gene expression of transthyretin (TTR),
      calcineurin, and NAD(P)H dehydrogenase quinone 2 (NQO2) were associated with
      memory deficits in aged animals. Decreased TTR gene expression could be
      attributed at least partially to diminish activity of C/EBP immediate-early gene
      cascade initiated by CREB since protein levels of C/EBP, a transcription factor
      regulating both TTR and NQO2 expression, was decreased in AI animals. Memory
      deficits were also found during aging in mice lacking TTR, a retinol transporter
      known to prevent amyloid-beta aggregation and plaque formation as seen in
      Alzheimer's disease. Treatment with retinoic acid reversed cognitive deficits in
      these knock-out mice as well as in aged rats. Our study provides genetic,
      behavioural and molecular evidence that TTR is involved in the maintenance of
      normal cognitive processes during aging by acting on the retinoid signalling
      pathway.

PMID- 17512092
TI  - Increasing CSF phospho-tau levels during cognitive decline and progression to
      dementia.
AB  - BACKGROUND: Little is known about longitudinal changes of cerebrospinal fluid
      (CSF) biomarkers during cognitive decline in neurodegenerative disease
      progression. OBJECTIVE: To investigate longitudinal changes in CSF biomarkers-
      total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during
      cognitive decline. METHODS: Forty memory clinic patients (47.5% females), aged
      61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and
      neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/
      1.8. Patients were divided into three groups based on baseline memory
      functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment
      (NIM). RESULTS: There was a significant increase in P-tau in the SIM-group during
      follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the
      SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients
      remained non-demented. T-tau- and Abeta42-levels did not change in any of the
      memory groups during follow-up. CONCLUSION: Increasing P-tau levels during
      cognitive decline and conversion to dementia suggest that P-tau may be useful as
      a longitudinal marker of the neurodegenerative process.

PMID- 17512094
TI  - Anti-tumor 12-deoxyphorbol esters from Euphorbia cornigera.
AB  - Nine (1-8 and 10) new and two (9 and 11) known compounds have been isolated from
      roots of Euphorbia cornigera Boiss. Their structure and relative stereochemistry
      were acquired through NMR ((1)H, (13)C, COSY-45, HOHAHA, HMQC, HMBC, NOE and
      HMBC) spectroscopic measurements. Compounds 1-10 were identified as diesters of
      13,20-O-diacyl and 11 as 13-O-acetyl of 12-deoxyphorbol. Cytotoxic activity of
      the compounds was investigated on human KB cells by reduction of MTT. Compounds 8
      10 displayed IC(50) of 0.8, 0.5, and 1.0 microg mL(-1), respectively, whereas the
      activity of rest of the compounds (1-7) was either very low or (11) zero even up
      to 1000 microg mL(-1). The inhibition of DNA synthesis through Trypan blue
      exclusion and Brd-U assay was investigation to figure out the role of compounds 8
      10 and concluded that these were responsible for the death of KB cells.
      Significant correlation has been found between the cytotoxicity and DNA cross
      link and DNA strand-break formation.

PMID- 17512095
TI  - [Prevention of delirium in an acute geriatric care unit].
AB  - PURPOSE: Delirium is the most common complication of hospitalization in frail
      elderly. The prognosis is poor with increased mortality and morbidity. Confusion
      results from one or several precipitating factors in patients at risk. In a
      randomized study, a preventive multicomponent intervention reduced the incidence
      of delirium by 40%. The aim of our study was to evaluate the efficacy of such a
      preventive strategy, in the setting of an acute geriatric care unit. METHODS: The
      study was conducted in a French 26-bed geriatric acute care ward. The primary
      outcome was the comparison of the incidence of delirium among patients aged 75
      years and older, before and after the implementation of a preventive strategy.
      The overall adherence of the ward staff to the prevention procedures was also
      determined. RESULTS: Before intervention, 367 patients were admitted (mean age:
      80.6 years). The incidence of delirium was of 8.99%. In the subgroup of 123
      demented patients, the incidence of delirium was of 15.4%. After intervention,
      372 patients were admitted (mean age 84.9). The incidence of delirium was of 2.4%
      (relative risk reduction of 73%, P=0.001). In the subgroup of 133 demented
      patients, the incidence of delirium was 5.3% (relative risk reduction of 66%,
      P=0.01). The ward staff applied the prevention procedures in 96% of the 10 230
      patients-day during the study period. CONCLUSION: This study shows that it is
      possible to apply the results of clinical research in clinical practice to
      prevent delirium in frail elderly hospitalized in an acute geriatric care unit.
      Such an easy preventive strategy could be applied in medical units admitting old
      patients at risk, in the context of a quality procedure.

PMID- 17512096
TI  - 'A Juggling Act': an analysis of the impact of providing clinical placements for
      pre-registration students on the organisation of community nursing and health
      visiting work.
AB  - Modernising policies for the NHS have aimed to strengthen the nursing workforce
      through enhancing professional roles and increasing the numbers of pre
      registration students. The current emphasis upon community based health care has
      led to an increase in the quantity and complexity of the workload for community
      nurses and health visitors, whilst at the same time educational developments have
      led to additional responsibilities supporting nursing students on community
      placements. These issues are explored in this paper which reports findings from a
      qualitative study in a large city based Primary Care Trust (PCT). The findings
      demonstrate that the provision of clinical placements for nursing students leads
      community nurses and health visitors to juggle the demands of their workload with
      meeting the needs of nursing students and clients. This requires a (re)
      organisation of their work, often impacting on the wider team. Additionally the
      nature of community nursing/health visiting work, shaped by time, space,
      resources and location, constrains opportunities for clinical learning. If
      government policies are to be implemented successfully, community nursing and
      health visiting staff require appropriate support to enable them to fulfil their
      educational and clinical roles.

PMID- 17512097
TI  - A qualitative study exploring the relationship between nursing and health
      promotion language, theory and practice.
AB  - The definitions and meaning qualified nurses employed in an acute NHS hospital
      setting in the UK gave to health education and health promotion practice and how
      these fitted established language and theory were investigated qualitatively.
      These concepts, and the concomitant frameworks and models of practice, have been
      the subject of considerable debate in the literature. While unresolved both in
      general and in nursing, a degree of theoretical convergence was established in
      the 1990s [Bunton, R., Macdonald, G., 1992. Health promotion: disciplines and
      diversity. Routledge, London; Maben, J.M., Macleod Clark, J. 1995. Health
      promotion: a concept analysis. Journal of Advanced Nursing 22, 1158-165] helped
      by The Ottawa Charter [WHO, 1986. Ottawa Charter for Health Promotion.
      http://www.who.int/hpr/archive/docs/ottawa.html]. For many of the participants in
      this study however, the meanings given to these concepts and the predominant use
      of health education were inconsistent with much of the language of the wider
      debate and this has potential implications for nurse education. For, if the
      findings are considered transferable then there is a need to develop education
      strategies and curricula that articulate the ideological foundations of policy
      and practice and to use mainstream terminology to assist nurses both to
      understand and contribute to the contemporary health promotion debate.

PMID- 17512098
TI  - Comparative reactogenicity and immunogenicity of 23 valent pneumococcal vaccine
      administered by intramuscular or subcutaneous injection in elderly adults.
AB  - 23 Valent pneumococcal vaccine is provided to the elderly through public health
      programs in many countries. However there is no clear recommendation regarding
      its route of administration (subcutaneous or intramuscular). In a randomised,
      observer blind study of 254 elderly subjects, the immunogenicity of a 23 valent
      pneumococcal vaccine was not influenced by its route of administration. A low
      rate of systemic adverse reactions was observed with the vaccine (subcutaneous
      and intramuscular both 6.3%). Local adverse reaction rates were; intramuscular
      7.1% and subcutaneous 18.9% and these were predicted by: * Pre-vaccination
      antibody titres>1 microg/ml, odds ratio 22.4 (8.06-74.84) compared with pre
      vaccination antibody titre<1 microg/ml. * Female gender, odds ratio 5.0 (1.85
      14.83) compared with male gender. * Subcutaneous injection route, odds ratio 3.20
      (1.13-9.13) compared with intramuscular injection route. * Female gender
      subcutaneous injection route, odds ratio 2.99 (1.10-8.70) compared with female
      gender intramuscular injection route. These data support the intramuscular
      injection of 23 valent pneumococcal vaccine, especially in elderly females.

PMID- 17512100
TI  - Place of birth and satisfaction with childbirth in Belgium and the Netherlands.
AB  - OBJECTIVE: to gain insight into the association between satisfaction with
      childbirth and place of birth, in the context of two maternity-care systems, in
      Belgium and the Netherlands. The Belgian and Dutch societies have many
      similarities but differ in the organisation of maternity care. The Dutch way of
      giving birth is well known for its high percentage of home births and its low
      medical intervention rate. In contrast, home births in Belgium are uncommon and
      the medical model is taken for granted. DESIGN: quantitative, comparative study
      using questionnaires to assess satisfaction with childbirth. SETTING: hospitals
      and independent midwifery practices in two comparable cities in Belgium and the
      Netherlands. PARTICIPANTS: two questionnaires were completed by 611 women, one at
      30 weeks of pregnancy and one within the first 2 weeks after childbirth, at home
      or in hospital. The women were invited to participate in the study by independent
      midwives and obstetricians during prenatal visits between 2004 and 2005.
      MEASUREMENTS AND FINDINGS: satisfaction with childbirth was measured by the
      Mackey Satisfaction with Childbirth Rating Scale, which takes into account the
      multi-dimensional nature of the concept. An analysis of variance with two fixed
      factors, planned place of birth and maternity-care system, shows that women who
      had planned for a home birth were more satisfied than women who had planned for a
      hospital birth. This was true in every subdimension of satisfaction. Belgian
      women were more satisfied with childbirth than their northern neighbours, in
      every subdimension. The higher satisfaction scores of the Belgian women accounted
      for both home and hospital births. KEY CONCLUSIONS: women who had planned a home
      birth were the most satisfied (in both countries), but Belgian women had higher
      satisfaction scores than Dutch women. This is paradoxical because a non-medical
      home context has a beneficial effect on satisfaction, whereas the Dutch non
      interventionist approach in maternity care does not yield the same effect.
      IMPLICATIONS FOR PRACTICE: medicalisation critics may be right about the
      iatrogenic effects of the medical approach on an individual level, but other
      social forces operate on the level of maternity-care systems.

PMID- 17512099
TI  - Enhanced delivery of immunoliposomes to human dendritic cells by targeting the
      multilectin receptor DEC-205.
AB  - Dendritic cells (DC) are specialized white blood cells that initiate and direct
      immune responses. Targeting DC surface proteins to deliver liposomes carrying
      antigens has demonstrated potential for eliciting antigen-specific immune
      responses. To evaluate this strategy in preclinical studies, we prepared anti
      human DEC-205 immunoliposomes (anti-hDEC-205 iLPSM) and compared their uptake by
      monocyte-derived DC (MoDC) and blood DC (BDC) with conventional liposomes
      (cLPSM). Antibody conjugation increased the number of immature MoDC taking up
      liposomes to 70-80%, regardless of the antibody coupled, whereas less than 20%
      endocytosed cLPSM. Anti-hDEC-205-IgG specifically increased cell uptake by 15%
      and the total iLPSM uptake six-fold. The non-specific iLPSM uptake was unlikely
      to be Fc receptor-mediated as excess immunoglobulins failed to block the uptake.
      Only a small population (7-24%) of mature MoDC took up cLPSM and control iLPSM.
      In contrast, approximately 70% of mature MoDC took up anti-hDEC-205 iLPSM,
      endocytosing 10-fold more iLPSM than the control iLPSM. Anti-hDEC-205 iLPSM
      uptake by CD1c+ BDC was similar to the immature MoDC, but was five-fold increased
      compared to the control iLPSM. Confocal microscopy confirmed that the anti-hDEC
      205 iLPSM were phagocytosed by DC and available for antigen processing. Thus, DEC
      205 is an effective target for delivering liposomes to human DC.

PMID- 17512101
TI  - The development and peer review of evidence-based guidelines to support midwifery
      led care in labour.
AB  - OBJECTIVE: to describe the development and peer review process for the third
      edition of evidence-based guidelines to support the provision of midwifery led
      care in labour. METHODS: the process of guideline development including
      identifying aspects of care for inclusion in the guidelines, the literature
      search strategy, bibliographic databases used, types of literature reviewed and
      rationale for inclusion are detailed. The process of formulating recommendations
      for practice is described. The peer review process, involving the principal
      stakeholders in the guidelines (midwives and representatives of maternity service
      users), the appraisal instrument used and issues identified during peer review
      are included. The third edition of the guidelines was commissioned in 2003 and
      completed during 2004. DISCUSSION: the development of the evidence-based
      guidelines is discussed in the context of contemporary debate related to
      guideline development and evidence-based practice including issues related to the
      nature and hierarchy of evidence, stakeholder involvement and sociological
      discourses of evidence-based medicine.

PMID- 17512102
TI  - Midwives' reflections on their educational programme: a traditional or problem
      based learning approach?
AB  - OBJECTIVE: to explore the longer-term effect of a problem-based learning (PBL)
      programme on midwives in practice. DESIGN: qualitative study. Graduates involved
      in an earlier study of the implementation of a PBL programme were interviewed
      between 5 and 6 years after graduating to explore the possible longer-term effect
      of a PBL programme on their practice as midwives. SETTING: Thames Valley
      University with graduates who had completed an 18-month programme on one of two
      campuses on a variety of clinical sites. PARTICIPANTS: interviews were held with
      four graduates who had completed their programme before the implementation of PBL
      and five who had completed a PBL programme. Key themes were identified and
      compared cross-sectionally. FINDINGS: midwives who had graduated from a PBL
      programme found that the approach was valuable in enabling them to access
      information and to develop a critical questioning approach. Some felt anxious at
      the beginning of their programme and said that they would have benefited from
      more direction and feedback from the facilitator early on in the programme. The
      focus on individual presentations sometimes inhibited the students learning from
      others in the group. The success of the PBL approach was felt to be dependent on
      the way in which the group worked together. The quality of the clinical
      placement, and the support of mentors and link teachers in the clinical setting,
      was a key factor in learning for students from both programmes. CONCLUSIONS: PBL
      has been incorporated into some programmes because it is thought to benefit
      practice disciplines, especially in a world of uncertain and changing evidence.
      However, no clear picture has emerged about the benefits of a PBL programme for
      midwifery education. IMPLICATIONS FOR PRACTICE: our findings have implications
      for curriculum development to ensure the potential benefits of PBL are realised
      in practice. This may include providing further guidance and feedback to
      students, particularly at the start of their programme. Further research using
      innovative methodologies is needed to critically assess the longer-term effect of
      this approach to education.

PMID- 17512104
TI  - Antioxidant responses of the earthworm Lampito mauritii exposed to Pb and Zn
      contaminated soil.
AB  - The aim of this study was to provide fundamental data on the biochemical analysis
      of antioxidant defences in the earthworm exposed to low levels (75, 150, 300 mg
      kg(-1) soil) of Pb and Zn. In order to attain this objective, adult Lampito
      mauritii were exposed to different doses of Pb and Zn separately for 28 days and
      the concentrations of oxidized and reduced glutathione, activities of glutathione
      S-transferase, glutathione peroxidase and glutathione reductase were assessed.
      Dose-dependent perturbations were observed in the glutathione-glutathione-S
      transferase system and other antioxidant enzymes during the early phase of the
      exposure to Pb. In the Zn exposed earthworm, the glutathione-glutathione-S
      transferase system remained stable and the stimulation of glutathione peroxidase
      and glutathione reductase activities occurred significantly only on day 14 at 300
      mg Zn kg(-1). It is concluded that the antioxidants are directly involved in the
      adaptive response of Lampito mauritii for survival in metal contaminated soil.

PMID- 17512105
TI  - Methodological and ethical issues in Internet-mediated research in the field of
      health: an integrated review of the literature.
AB  - The advantages and disadvantages of using the Internet in both qualitative and
      quantitative researches in the field of health are readily available in the
      literature, but little examination has been made of the factors to be considered
      in developing and running Internet-mediated research. A bibliographic search of
      English language publications indexed in eight computerized databases (EBSCO,
      EMBASE, MedLine, PsycInfo, CINAHL, PubMed, Cochrane, and TRIP) was undertaken
      with no limit set for the data of publication. The keywords Internet, research,
      quality, credibility, reliability, and validity were used in all possible
      combinations, and mappings to headings made wherever possible. The search
      revealed three key areas in setting up and undertaking Internet-mediated
      research: addressing sampling biases, ensuring ethical practice, and exploring
      the validity of data collected using an online interface. This paper contributes
      to the ongoing development of quality standards in the conduct and write-up of
      Internet-mediated research in the field of health.

PMID- 17512106
TI  - The effect of a naturalistic stressor on frontal EEG asymmetry, stress, and
      health.
AB  - The aim of the current study was to investigate the effect of a naturalistic
      stressor, examination stress, on frontal EEG asymmetry, psychological stress,
      hormonal stress, and negative health. Forty-nine subjects were tested during
      periods of low and high examination stress. During the high examination stress
      period, subjects reported higher levels of stress on the Spielberger State
      Anxiety Inventory and Cohen's Perceived Stress Scale. However, no change in
      cortisol was detected across the two sessions. Furthermore, a shift from
      relatively greater left frontal activity during the low examination session to
      relatively greater right frontal activity during the high examination session was
      also found. Moreover, the increasing right frontal activity asymmetry associated
      with the high exam session compared to the low exam session correlated with
      increasing reports of negative health. No evidence was found for the prediction
      that cortisol mediated either the relationship between examination stressor and
      right frontal asymmetry or between right frontal asymmetry and negative health.
      In conclusion, while the findings from this study are compelling, the mechanism
      mediating increases in psychological stress, relatively greater right frontal
      activity, and increases in negative health from naturally occurring stressors is
      in need of further investigation.

PMID- 17512107
TI  - Towards an ecologically meaningful classification of the flow biotope for river
      inventory, rehabilitation, design and appraisal purposes.
AB  - Recent research into the physical and ecological status of rivers has focused
      upon rapid field-based assessments of mesoscale habitat features in order to
      satisfy international regulatory requirements for habitat inventory and
      appraisal. Despite the low cost and time efficient nature of rapid field surveys,
      the robustness of such techniques remains uncertain. This paper uses data from
      over 4,000 surveyed UK river reaches in the UK River Habitat Survey (RHS)
      database in order to seek linkages between surface flow conditions (flow
      biotopes), local channel morphology (physical biotopes) and biologically distinct
      vegetative and minerogenic habitat units (functional habitats). Attempts to
      identify one-to-one connections between surface flow types, units of channel
      morphology and functional habitats oversimplify a complex and dynamic hydraulic
      environment. Instead, a nested hierarchy of reach-scale physical and ecological
      habitat structures exists, characterised by transferable assemblages of habitat
      units. Five flow biotopes show strong correlations with functional habitats, and
      differing combinations of three of these account for over 60% of the distribution
      for all functional habitats. On this basis, a classification of environments for
      ecological purposes is proposed. Principal components analysis and agglomerative
      hierarchical clustering analysis are employed to objectively validate the
      proposed classification. Flow biotope assemblages may also represent reach-scale
      channel morphologies (step-pool, riffle-pool and glide-pool), although functional
      habitats exhibit differing 'preferences' for rougher or more tranquil
      environments within these. While the data and analysis are specific to the UK
      RHS, the methods and findings have wider application in situations, where rapid
      field appraisal methods and associated databases are deployed in water resource
      inventory and river rehabilitation design.

PMID- 17512108
TI  - A proposal to clarify the relationship between the thermal index and the
      corresponding risk to the patient.
AB  - The thermal index (TI) displayed on the screens of most modern diagnostic
      ultrasound machines is linearly proportional to the absorbed power or,
      equivalently, to the in-situ intensity or temperature rise. Users are instructed
      to interpret the TI as a "relative indication of bioeffect risk." The thermal
      dose is a well-known empirical relationship between the temperature T of a
      biological system and the time t needed for that temperature to induce a
      deleterious effect. For any two temperatures, T1 and T2, and the corresponding
      times t1 and t2, required to produce the same level of effect, this general
      relation holds: t1/t2=RT2-T1, where R is the thermal normalization constant.
      Hence, it is experimentally determined that the rate of induction, or risk, of a
      thermal effect increases exponentially with temperature. Because exponential
      relationships are not intuitive to many users, there is a significant potential
      for underestimation of the thermal risk associated with exposure to diagnostic
      ultrasound. To better quantify this risk and thereby make the displayed
      information more useful, the current linear display of the calculated value of
      the thermal index, i.e., of TIcur, should be altered to an exponential form based
      on the thermal dose and representing the excess risk associated with the
      exposure: TInew=(RTIcur-1)/(R-1). This expression has the advantage that for the
      usual choice of R=4 for T<or=43 degrees C, TInew approximately TIcur in the range
      most often seen onscreen, i.e., TIcur<1.2, minimizing any confusion during a
      transition from TIcur to TInew. For the relatively rare but potentially much more
      serious circumstances when TIcur>3.5, the displayed TInew>>TIcur, consistent with
      empirical observations of the likelihood of harm. Additional advantages also
      obtain.

PMID- 17512109
TI  - Interview with Dr Guido Barbagli. Substitution urethroplasty: which tissues and
      techniques are optimal for urethral replacement? Interview by Christine McKillop.

PMID- 17512110
TI  - A mathematical model of P53 gene regulatory networks under radiotherapy.
AB  - P53, a vital anticancer gene, controls the transcription and translation of a
      series of genes, and implement the cell cycle arrest and cell apoptosis by
      regulating their complicated signal pathways. Under radiotherapy, cell can
      trigger internal self-defense mechanisms in fighting against genome stresses
      induced by acute ion radiation (IR). To simulate the investigating of cellular
      responding acute IR at single cell level further, we propose a model of P53 gene
      regulatory networks under radiotherapy. Our model can successfully implement the
      kinetics of double strand breaks (DSBs) generating and their repair, ataxia
      telangiectasia mutated (ATM) activation, as well as P53-MDM2 feedback regulating.
      By comparing simulations under different IR dose, we can try to find the optimal
      strategy in controlling of IR dose and therapy time, and provide some theoretical
      analysis to obtain much better outcome of radiotherapy further.

PMID- 17512111
TI  - Progesterone, glucocorticoid, but not estrogen receptor mRNA is altered in breast
      cancer stroma.
AB  - Our laboratory has previously found that anti-mitogenic nuclear receptor mRNA is
      elevated in late stage tumours and this study was performed to scrutinize the
      possibility of cancer-stroma crosstalk using hormone signaling in these tissues.
      RNA levels in stromal tissue were examined for the estrogen alpha, estrogen beta,
      androgen, progesterone and glucocorticoid nuclear receptors by a semi
      quantitative PCR. Significant differences in expression between the cancer stroma
      and control tissue were seen, analyzing for both cancer grade and estrogen
      receptor status. Stroma and control tissue were significantly different for the
      progesterone and glucocorticoid nuclear receptors (p=5.908 x 10(-7) and 2.761 x
      10(-5), respectively). Glucocorticoid receptor also showed a significant increase
      to mRNA levels in the stroma of estrogen receptor negative tumours (p=5.85 x 10(
      5)). By contrast, the estrogen receptors alpha and beta, those most closely
      associated with breast tissue growth, showed no significant change in mRNA
      (p=0.372 and 0.655, respectively). Androgen receptor mRNA also remained
      unaffected (p=0.174).

PMID- 17512112
TI  - Chemical or electrochemical techniques, followed by ion exchange, for recycle of
      textile dye wastewater.
AB  - This paper examines the use of chemical or electrocoagulation treatment process
      followed by ion-exchange process of the textile dye effluent. The dye effluent
      was treated using polymeric coagulant (cationic dye-fixing agent) or
      electrocoagulation (iron and aluminum electrode) process under various conditions
      such as various current densities and effect of pH. Efficiencies of COD
      reduction, colour removal and power consumption were studied for each process.
      The chemical or electrochemical treatment are indented primarily to remove colour
      and COD of wastewater while ion exchange is used to further improve the removal
      efficiency of the colour, COD, Fe concentration, conductivity, alkalinity and
      total dissolved solids (TDS). From the results chemical coagulation, maximum COD
      reduction of about 81.3% was obtained at 300 mg/l of coagulant whereas in
      electrocoagulation process, maximum COD removal of about 92.31% (0.25 A/dm2) was
      achieved with energy consumption of about 19.29 k Wh/kg of COD and 80% (1A/dm(2))
      COD removal was obtained with energy consumption of about 130.095 k Wh/kg of COD
      at iron and aluminum electrodes, respectively. All the experimental results,
      throughout the present study, have indicated that chemical or electrocoagulation
      treatment followed by ion-exchange methods were very effective and were capable
      of elevating quality of the treated wastewater effluent to the reuse standard of
      the textile industry.

PMID- 17512113
TI  - Study of the conditions affecting dye adsorption on titania films and of their
      effect on dye photodegradation rates.
AB  - Nanocrystalline titania films have been deposited on glass slides by the sol-gel
      technique in the presence of surfactant, which plays the role of template of the
      nanostructure. Several different dyes, both anionic and cationic, have been
      adsorbed on these films from aqueous solutions. Some of these dyes were adsorbed
      at large quantities some at lower quantities. Some of them were adsorbed in
      monomeric form and others formed aggregates. Aggregates are easily distinguished
      by absorption spectrophotometry, since absorption of light is observed at a
      different wavelength than monomer absorption in a dilute solution. In all cases,
      aggregation demonstrated a hypsochromic shift, indicating repulsive interactions,
      which are justified in view of the fact that titania surface is charged and that
      adsorbed molecules are aligned in parallel. The above titania films are
      hydroxylated. Therefore, cationic dyes were readily adsorbed. Anionic dyes could
      be adsorbed only from aqueous solutions brought at low pH. Photodegradation rates
      of adsorbed dyes were generally fast since these films are efficient
      photocatalysts. Nevertheless, photodegradation of an adsorbed dye was faster when
      the quantity of the dye was smaller. When the adsorbed dyes formed aggregates,
      aggregation had adverse effect on photodegradation rates.

PMID- 17512114
TI  - Organics removal of combined wastewater through shallow soil infiltration
      treatment: a field and laboratory study.
AB  - Soil infiltration treatment (SIT) was proved to be an effective and low-cost
      treatment technique for decentralized effluents in the areas without perfect
      sewage systems. Field-scale experiments were conducted under several conditions
      to assess organics removals through a shallow soil infiltration treatment (SSIT,
      with effective depth 0.3m) of combined wastewater (discharge from toilets,
      restaurants and a gas station), while bench-scale soil column experiments were
      performed in laboratory in parallel to investigate biological and abiological
      effects of this kind of system. From the start-up to the 10th month, the field
      SSIT trenches experienced the lowest and highest temperatures of the operation
      period in Shanghai and exhibited effective organics removals after maturation,
      with the highest removal rate 75.8% of chemical oxygen demand (COD), highest
      ultraviolet absorption at 254 nm (UV(254)) decrease by 67.2% and 35.2-100%
      removals of phenolic and phthalate pollutants. The laboratory results indicated
      that more organics could be removed in room-temperatured (25+/-2 degrees C) SSIT
      systems under different influent COD concentrations from 45 mg/l to 406 mg/l, and
      the highest total COD removal rate could reach 94.0%, in which biological effect
      accounted for 57.7-71.9%. The results showed that temperature and hydraulic
      loading rate were the most important factors influencing the removals of COD and
      organic pollutants in SSIT.

PMID- 17512115
TI  - Role of spinal metabotropic glutamate receptor subtype 5 in the development of
      tolerance to morphine-induced antinociception in rat.
AB  - Prolonged intrathecal (i.t.) administration of morphine results in tolerance to
      morphine-induced antinociception. We found that co-administration of selective
      metabotropic glutamate receptor subtype 5 antagonist MPEP with morphine could
      suppress the loss of morphine-induced antinociception and inhibit the development
      of tolerance to morphine-induced antinociceptive effect. Whereas, the specific
      metabotropic glutamate receptor subtype 5 agonist CHPG does the opposite. As the
      activation of NMDA receptor after chronic morphine administration has been
      verified, we suppose there is an enhanced activation of mGluR5 during the
      development of tolerance to morphine-induced antinociception. Activation of
      mGluR5 may mobilize the release of intracellular Ca(2+) and activate PKC, leading
      to morphine-induced antinociception suppression. We conclude that mGluR5
      contributes to the development of tolerance to morphine-induced antinociception
      after chronic morphine exposure.

PMID- 17512116
TI  - Postnatal developmental changes in the expression of ErbB receptors in murine
      Pacinian cospucles.
AB  - Neuregulins and their signaling ErbB receptors play a critical role during the
      development of the mammalian peripheral nervous system, including some kinds of
      mechanoreceptors such as the Pacinian corpuscles which become structurally and
      functionally mature postnatally. In this study, we investigated whether or not
      ErbBs in Pacinian corpuscles undergoes developmental changes, as well as if their
      expression depends on the innervation. Pacinian corpuscles from 7-day- and 3
      month-old mice were assessed for the immunohistochemical detection of EGFR or
      ErbB1, ErbB2, ErbB3 and ErbB4. The effect of denervation on the expression of
      ErbBs in mature Pacinian corpuscles was also analyzed. Developing 7-day-old
      Pacinian corpuscles express ErbB2 and ErbB3 immunoreactivity in the inner-core
      (regarded as modified Schwann cells), whereas the mature 3-month-old Pacinian
      corpuscles exclusively displayed ErbB4 immunoreactivity in the outer core and the
      capsule (regarded as endoneurial and perineurial cells). Denervation was without
      effect on the ErbB expression. Present results demonstrate maturational related
      changes and cell segregation in the expression of ErbB receptors by murine
      Pacinian corpuscles, and that this expression is independent of the innervation.

PMID- 17512117
TI  - Short-interval intracortical inhibition is modulated by high-frequency peripheral
      mixed nerve stimulation.
AB  - Cortical excitability can be modulated by manipulation of afferent input. We
      investigated the influence of peripheral mixed nerve stimulation on the
      excitability of the motor cortex. Motor evoked potentials (MEPs), short-interval
      intracortical inhibition (SICI) and intracortical facilitation (ICF) in the right
      abductor pollicis brevis (APB), extensor carpi radialis (ECR) and first dorsal
      interosseous (FDI) muscles were evaluated using paired-pulse transcranial
      magnetic stimulation (TMS) before and after high-frequency peripheral mixed nerve
      stimulation (150 Hz, 30 min) over the right median nerve at the wrist. The MEP
      amplitude and SICI of the APB muscle decreased transiently 0-10 min after the
      intervention, whereas the ICF did not change. High-frequency peripheral mixed
      nerve stimulation reduced the excitability of the motor cortex. The decrement in
      the SICI, which reflects the function of GABA(A)ergic inhibitory interneurons,
      might compensate for the reduced motor cortical excitability after high-frequency
      peripheral mixed nerve stimulation.

PMID- 17512118
TI  - Vitamin C antioxidant effects in hippocampus of adult Wistar rats after seizures
      and status epilepticus induced by pilocarpine.
AB  - Vitamin C (VIT C) is an exogenous antioxidant able to alter the brain oxidative
      stress. Antioxidant properties have been showed in seizures and status
      epilepticus (SE) induced by pilocarpine in adult rats. This present study was
      aimed at was investigating the VIT C effects on latency to first seizure, in
      percentage of seizures, mortality rate, as well as hippocampal lipid peroxidation
      levels and catalase activity after seizures and SE. The VIT C effects were
      investigated after the pretreatment with dose 250 mg/kg, i.p., 30 min before
      pilocarpine administration (400mg/kg, s.c., pilocarpine group (P400)). The VIT C
      increase the latency to first seizure and decrease the mortality rate and lipid
      peroxidation levels. In P400+VIT C and VIT C groups were observed an increase in
      hippocampal catalase activity. Our results suggests that the vitamin C can exert
      antioxidant and anticonvulsive effects in adult rats, suggesting that this
      vitamin can be able by reduction of lipid peroxidation content and increased of
      catalase enzymatic activity which cerebral compensatory mechanisms in free
      radical formation during SE.

PMID- 17512119
TI  - Brightness processing in the visual cortex.
AB  - Single cell recordings have shown that some cells in the primary visual cortex
      (V1) signal surface brightness. However, fMRI experiments have found brightness
      related activation only in the higher cortical areas. In a psychophysical setup,
      we were able to dissociate the reduction of brightness caused by Gabor flankers,
      similar to the receptive fields in V1, from the edge induced brightness change.
      The former resemble the single cell recording results and the latter the fMRI
      results.

PMID- 17512120
TI  - Plasma corticosterone, dexamethasone (DEX) suppression and DEX/CRH tests in a rat
      model of genetic vulnerability to depression.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis is hyperactive in major depressive
      disorder (MDD), and baseline cortisol levels are usually elevated in MDD
      patients, with alterations of the circadian hormone secretion pattern. The
      dexamethasone (DEX) suppression test (DST) has been extensively applied to
      diagnose a dysregulation of the HPA axis in MDD, but it has only a limited
      sensitivity to, and specificity for, depression. The DEX/CRH test, which combines
      the DST with a corticotropin-releasing hormone (CRH) challenge, has proved more
      reliable to show HPA axis dysfunction in MDD. We have applied these two tests to
      a putative model of vulnerability to depression in rodents, the Roman high-(RHA)
      and low-(RLA) Avoidance rat lines. As compared to RHA, RLA rats are behaviorally
      inhibited, they show an exaggerated response of the HPA axis to stress, and are
      more prone to develop depressive-like features when exposed to chronic stress.
      Our results show that (a) there were no significant differences in circadian
      plasma corticosterone (CORT) levels and/or secretion patterns between the two
      lines; (b) in the DST test, CORT was suppressed to the same extent in RHA and RLA
      rats; and c) in the DEX/CRH test, areas-under-the-curve (AUCs) and CORT delta
      (peak minus baseline) responses were significantly larger in RLA rats. One
      possible interpretation of these data is that an increased response to CRH could
      be a trait marker (or endophenotype) for depression, whereas alterations of
      circadian glucocorticoid secretion patterns and non-suppression of the daily
      glucocorticoid rise by dexamethasone could be state markers, i.e. features that
      are only present during depressive episodes.

PMID- 17512121
TI  - Early and adverse experiences with sex and alcohol are associated with adolescent
      drinking before and during pregnancy.
AB  - The goal of this study was to examine the effects of early and adverse
      experiences with sex and alcohol on adolescent drinking the year before and
      during pregnancy. Pregnant adolescents, recruited at an outpatient prenatal
      clinic, were interviewed about their substance use. A subsample was asked about
      their first sexual experiences. Associations among early experiences with alcohol
      and sex and drinking before and during pregnancy were examined. Early age at
      first alcoholic drink predicted problem alcohol use before pregnancy and drinking
      during pregnancy. Coercive first coitus was not associated with alcohol use, but
      drinking during first coitus predicted problem alcohol use before pregnancy as
      well as drinking during the first trimester of pregnancy. In sum, early use of
      alcohol and use of alcohol during first coitus may be risk factors for
      problematic alcohol use before pregnancy and during pregnancy among childbearing
      teenagers. Implications for the health of adolescent mothers and their offspring
      are discussed.

PMID- 17512122
TI  - A role for the antioxidant defense system in preventing the transmission of HIV.
AB  - Twenty-five years of experience with the human immunodeficiency virus (HIV) have
      established that it is relatively difficult to transmit. The chance of medical
      personnel acquiring this virus by needlestick injury is only 0.3%. Similarly, the
      odds of an HIV-positive male infecting a female partner during one unprotected
      sexual encounter is 9 in 10,000. Furthermore, the per-act risk of infection from
      penal-anal intercourse with an HIV-positive male partner is established at 82 in
      10,000. Since those who are not infected by such exposures do not develop
      antibodies against HIV, there must be an earlier line of defense. The global
      diffusion pattern of HIV/AIDS is strongly suggestive of a protective role for the
      trace element selenium. It is hypothesized here that the body's antioxidant
      defense system, especially the selenoenzyme glutathione peroxidase, acts as an
      initial defense against viral infection, preceding the formation of antibodies.
      For this reason, HIV is having its greatest difficulty in infecting those with
      diets elevated in amino acids and the trace element selenium which, when eaten
      together, stimulate the body's production of glutathione peroxidase.

PMID- 17512123
TI  - Epigenetic mechanisms may underlie the increased risk for psychosis among
      immigrants.

PMID- 17512125
TI  - Antiandrogenic effect of isotretinoin: is the retina involved in mechanism of
      action?
AB  - Isotretinoin (13-cis retinoic acid) has been the most effective available drug
      for severe acne vulgaris. Isotretinoin inhibits proliferation of sebocytes and
      can also reduce lipid synthesis, but its antiandrogenic effect remains uncertain.
      Decreased dark adaptation is one of the commonest ophthalmological adverse events
      of isotretinoin, which could be transient and permanent as well. Isotretinoin
      causes loss of night vision by slowing rhodopsin regeneration and chromophore
      recycling by the inhibition of 11-cis retinol dehydrogenase. The primary
      photoreceptors of the circadian pacemaker are the melanopsin containing
      intrinsically photosensitive retinal ganglion cells (ipRGC). Since the
      photochemistry of melanopsin is very similar to other opsin photopigments, and it
      is known that melanopsin uses the same retinaldehyde chromophore, it is
      hypothesized here that isotretinoin may exert inhibitory effect on chromophore
      regeneration in ipRGCs similar to what is seen in rod and cone cells, thus
      enabling to alter circadian and circannual rhythms. Mechanism of action of
      isotretinoin may involve neuroendocrine-reproductive axis in its antiandrogenic
      effect, and melatonin may mediate this action.

PMID- 17512124
TI  - Up-regulation of tumor suppressor genes might promote the malignant phenotype of
      cancer cells.

PMID- 17512126
TI  - Phase I/II trial of sequential chemoradiotherapy using a novel hypoxic cell
      radiosensitizer, doranidazole (PR-350), in patients with locally advanced non
      small-cell lung Cancer (WJTOG-0002).
AB  - PURPOSE: This Phase I/II trial was conducted to assess the efficacy and safety of
      PR-350, a novel hypoxic cell radiosensitizer, when administered with thoracic
      radiation therapy (RT) after induction chemotherapy (CT) for locally advanced non
      small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Two cycles of cisplatin
      (80 mg/m(2)) and paclitaxel (180 mg/m(2)), or carboplatin (AUC = 6) and
      paclitaxel (200 mg/m(2)) were given before RT of 60 Gy in 30 fractions. In the
      Phase I portion, the starting dosage of PR-350 was 10 daily administrations (2000
      mg/m(2)) in combination with RT, and this number was increased in increments of
      10 for successive groups to 30 doses. RESULTS: In total, 37 patients were
      enrolled. In Phase I (n = 20), PR-350 could be administered 30 times with
      concurrent thoracic RT. Thus, in Phase II (n = 17), PR-350 was administered 30
      times. The major toxicity was radiation pneumonitis, with Grade 3 or more
      pneumonitis noted in 6 patients (16%) including 2 with treatment-related deaths.
      However, no Grade 3 or more esophageal toxicity was noted, and only Grade 1
      peripheral neuropathy was noted in 9 patients (24%). For all 37 patients, the
      median survival time (MST) and the 2-year survival rate were 15.9 months and 24%,
      respectively. For 18 patients receiving 21 to 30 doses of PR-350, the MST and 2
      year survival rate were 20.9 months and 33%, respectively. CONCLUSIONS: Thoracic
      RT combined with 30 daily administrations of PR-350 after induction CT was well
      tolerated and promising for locally advanced NSCLC.

PMID- 17512127
TI  - Health-related quality of life in patients with locally advanced prostate cancer
      after 76 Gy intensity-modulated radiotherapy vs. 70 Gy conformal radiotherapy in
      a prospective and longitudinal study.
AB  - PURPOSE: To compare quality of life (QoL) after 70 Gy conformal radiotherapy with
      QoL after 76 Gy intensity-modulated radiotherapy (IMRT) in patients with locally
      advanced prostate carcinoma. METHODS AND MATERIALS: Seventy-eight patients with
      locally advanced prostate cancer were treated with 70 Gy three-field conformal
      radiotherapy, and 92 patients received 76 Gy IMRT with fiducial markers for
      position verification. Quality of life was measured by RAND-36, the European
      Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ
      C30(+3)), and the prostate-specific EORTC QLQ-PR25, before radiotherapy
      (baseline) and 1 month and 6 months after treatment. Quality of life changes in
      time (baseline vs. 1 month and baseline vs. 6 months) of > or =10 points were
      considered clinically relevant. RESULTS: Differences between the treatment groups
      for QoL changes over time occurred in several QoL domains. The 76-Gy group
      revealed no significant deterioration in QoL compared with the 70-Gy group. The
      IMRT 76-Gy group even demonstrated a significantly better change in QoL from
      baseline to 1 month in several domains. The conformal 70-Gy group revealed
      temporary deterioration in pain, role functioning, and urinary symptoms; for the
      IMRT 76-Gy group a better QoL in terms of change in health existed after 1 month,
      which persisted after 6 months. For both treatment groups temporary deterioration
      in physical role restriction occurred after 1 month, and an improvement in
      emotional role restriction occurred after 6 months. Sexual activity was reduced
      after treatment for both groups and remained decreased after 6 months.
      CONCLUSIONS: Intensity-modulated radiotherapy and accurate position verification
      seem to provide a possibility to increase the radiation dose for prostate cancer
      without deterioration in QoL.

PMID- 17512128
TI  - TRAIL death receptor-4 expression positively correlates with the tumor grade in
      breast cancer patients with invasive ductal carcinoma.
AB  - PURPOSE: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL)
      selectively induces apoptosis in cancer cells but not in normal cells, and a
      number of clinical trials have recently been initiated to test the safety and
      antitumoral potential of TRAIL in cancer patients. Four different receptors have
      been identified to interact with TRAIL: two are death-inducing receptors (TRAIL
      R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4
      [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL
      induced cytotoxicity. Because high levels of DcR2 expression have recently been
      correlated with carcinogenesis in the prostate and lung, this study investigated
      the importance of TRAIL and TRAIL receptor expression in breast cancer patients
      with invasive ductal carcinoma, taking various prognostic markers into
      consideration. METHODS AND MATERIALS: Immunohistochemical analyses were performed
      on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL
      receptor-specific antibodies. Age, menopausal status, tumor size, lymph node
      status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular
      tumor extension, presence of an extensive intraductal component, multicentricity,
      estrogen and progesterone receptor status, and CerbB2 expression levels were
      analyzed with respect to TRAIL/TRAIL receptor expression patterns. RESULTS: The
      highest TRAIL receptor expressed in patients with invasive ductal carcinoma was
      DR4. Although progesterone receptor-positive patients exhibited lower DR5
      expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL
      expressions. CONCLUSIONS: DR4 expression positively correlates with the tumor
      grade in breast cancer patients with invasive ductal carcinoma.

PMID- 17512129
TI  - A multiplan treatment-planning framework: a paradigm shift for intensity
      modulated radiotherapy.
AB  - PURPOSE: To describe a multiplan intensity-modulated radiotherapy (IMRT) planning
      framework, and to describe a decision support system (DSS) for ranking multiple
      plans and modeling the planning surface. METHODS AND MATERIALS: One hundred
      twenty-five plans were generated sequentially for a head-and-neck case and a
      pelvic case by varying the dose-volume constraints on each of the organs at risk
      (OARs). A DSS was used to rank plans according to dose-volume histogram (DVH)
      values, as well as equivalent uniform dose (EUD) values. Two methods for ranking
      treatment plans were evaluated: composite criteria and pre-emptive selection. The
      planning surface determined by the results was modeled using quadratic functions.
      RESULTS: The DSS provided an easy-to-use interface for the comparison of multiple
      plan features. Plan ranking resulted in the identification of one to three
      "optimal" plans. The planning surface models had good predictive capability with
      respect to both DVH values and EUD values and generally, errors of <6%. Models
      generated by minimizing the maximum relative error had significantly lower
      relative errors than models obtained by minimizing the sum of squared errors.
      Using the quadratic model, plan properties for one OAR were determined as a
      function of the other OAR constraint settings. The modeled plan surface can then
      be used to understand the interdependence of competing planning objectives.
      CONCLUSION: The DSS can be used to aid the planner in the selection of the most
      desirable plan. The collection of quadratic models constructed from the plan data
      to predict DVH and EUD values generally showed excellent agreement with the
      actual plan values.

PMID- 17512130
TI  - Primary vaginal cancer treated with concurrent chemoradiation using Cis-platinum.
AB  - PURPOSE: To evaluate the feasibility of concurrent weekly Cis-platinum
      chemoradiation (CRT) in the curative treatment of primary vaginal cancer.
      METHODS: A retrospective review was performed of all primary vaginal cancer
      patients treated with curative intent at the Ottawa Hospital Regional Cancer
      Centre between 1999 and 2004 using concurrent Cis-platinum CRT. RESULTS: Twelve
      patients were treated with concurrent weekly CRT. The median age at diagnosis was
      56 years (range, 34-69 years), and the median follow-up was 50 months (range, 11
      75 months). Ten patients (83%) were diagnosed with squamous cell carcinoma and 2
      patients (17%) with adenocarcinoma. The distribution according to stage was as
      follows: 6 (50%) Stage II, 4 (33%) Stage III, and 2 (17%) Stage IVA. All patients
      received pelvic external beam radiotherapy (EBRT) concurrently with weekly
      intravenous Cis-platinum chemotherapy (40 mg/m(2)) followed by brachytherapy
      (BT). The median dose of EBRT was 4500 cGy given in 25 fractions over 5 weeks.
      Ten patients received interstitial BT, and 2 patients received intracavitary BT,
      with the median dose being 3000 cGy. The 5-year overall survival, progression
      free survival, and locoregional progression-free survival rates were 66%, 75%,
      and 92%, respectively. Late toxicity requiring surgery occurred in 2 patients
      (17%). CONCLUSIONS: For the treatment of primary vaginal cancer, it is feasible
      to deliver concurrent weekly Cis-platinum chemotherapy with high-dose radiation,
      leading to excellent local control and an acceptable toxicity profile.

PMID- 17512131
TI  - Preclinical biologic assessment of proton beam relative biologic effectiveness at
      Proton Therapy Center Houston.
AB  - The clinical use of protons for the treatment of cancer is one of the most
      technologically advanced forms of therapy. The newly commissioned M.D. Anderson
      Cancer Center, Proton Therapy Center Houston is one of the newest facilities
      offering a complete range of advanced proton therapies designed specifically to
      minimize treatment-related normal tissue toxicity. As an integral part of the
      clinical commissioning of this proton beam, we performed an in vivo assessment of
      the relative biologic effectiveness of the 250-MeV protons relative to standard
      cobalt(60) using the jejunal crypt microcolony assay in mice. Our data are
      consistent with a generic relative biologic effectiveness of 1.1, and this
      relative biologic effectiveness is in agreement with that used to describe most
      other clinical proton therapy beams worldwide.

PMID- 17512132
TI  - Phase I trial of gross total resection, permanent iodine-125 brachytherapy, and
      hyperfractionated radiotherapy for newly diagnosed glioblastoma multiforme.
AB  - PURPOSE: To evaluate the feasibility of gross total resection and permanent I-125
      brachytherapy followed by hyperfractionated radiotherapy for patients with newly
      diagnosed glioblastoma. METHODS AND MATERIALS: From April 1999 to May 2002, 21
      patients with glioblastoma multiforme were enrolled on a Phase I protocol
      investigating planned gross total resection and immediate placement of permanent
      I-125 seeds, followed by postoperative hyperfractionated radiotherapy to a dose
      of 60 Gy at 100 cGy b.i.d., 5 days per week. Median age and Karnofsky performance
      status were 50 years (range, 32-65 years) and 90 (range, 70-100), respectively.
      Toxicity was assessed according to Radiation Therapy Oncology Group criteria.
      RESULTS: Eighteen patients completed treatment according to protocol. The median
      preoperative tumor volume on magnetic resonance imaging was 18.6 cm(3) (range,
      4.4-41.2 cm(3)). The median brachytherapy dose measured 5 mm radially outward
      from the resection cavity was 400 Gy (range, 200-600 Gy). Ten patients underwent
      12 reoperations, with 11 of 12 reoperations demonstrating necrosis without
      evidence of tumor. Because of high toxicity, the study was terminated early.
      Median progression-free survival and overall survival were 57 and 114 weeks,
      respectively, but not significantly improved compared with historical patients
      treated at University of California, San Francisco, with gross total resection
      and radiotherapy without brachytherapy. CONCLUSIONS: Treatment with gross total
      resection and permanent I-125 brachytherapy followed by hyperfractionated
      radiotherapy as performed in this study results in high toxicity and reoperation
      rates, without demonstrated improvement in survival.

PMID- 17512134
TI  - Optimized dose coverage of regional lymph nodes in breast cancer: the role of
      intensity-modulated radiotherapy.
AB  - PURPOSE: To determine whether the use of intensity-modulated radiotherapy (IMRT)
      would lead to improved dosimetry for the breast and regional nodes. METHODS AND
      MATERIALS: Ten patients with left-sided breast cancer were selected. The clinical
      target volume included left breast and internal mammillary (IM), supraclavicular
      (SC), and axillary (AX) nodes. The critical structures included heart, right and
      left lungs, contralateral breast, esophagus, thyroid, and humeral head.
      Conventional and a series of IMRT plans were generated for comparison. RESULTS:
      The average heart D(3) was reduced from 31.4 +/- 18.9 with three-dimensional
      conformal radiotherapy (3D-CRT) to 15 +/- 7.2 Gy with 9-field (9-FLD IMRT). The
      average left lung D(30) was also decreased from 27.9 +/- 11.5 Gy (3D-CRT) to 12.6
      +/- 8.2 Gy (9-FLD IMRT). The average contralateral breast D(2) was reduced from
      4.4 +/- 5.3 Gy (3D-CRT) to 1.8 +/- 1.2 Gy (4-FLD IMRT). Esophagus D(2) was
      increased from 9.3 +/- 8.1 Gy (3D-CRT) to 29.4 +/- 5.4 (9-FLD IMRT); thyroid
      D(50) was increased from 0.9 +/- 0.6 Gy (3D-CRT) to 11.9 +/- 6.6 (9-FLD IMRT);
      humeral head D(2) was increased from 36.1 +/- 13.1 Gy (3D-CRT) to 39.9 +/- 6.5 (9
      FLD IMRT). CONCLUSIONS: The use of IMRT improves breast and regional node
      coverage while decreasing doses to the lungs, heart, and contralateral breast
      when compared with 3D-CRT. Doses to esophagus, thyroid, and humeral head,
      however, were increased with IMRT.

PMID- 17512133
TI  - Ultrasound-guided transrectal implantation of gold markers for prostate
      localization during external beam radiotherapy: complication rate and risk
      factors.
AB  - PURPOSE: To report the complication rate and risk factors of transrectally
      implanted gold markers, used for prostate position verification and correction
      procedures. METHODS AND MATERIALS: In 209 consecutive men with localized prostate
      cancer, four gold markers (1 x 7 mm) were inserted under ultrasound guidance in
      an outpatient setting, and the toxicity was analyzed. All patients received a
      questionnaire regarding complications after marker implantation. The
      complications and risk factors were further evaluated by reviewing the medical
      charts. RESULTS: Of the 209 men, 13 (6.2%) had a moderate complication,
      consisting of pain and fever that resolved after treatment with oral medication.
      In 1.9% of the men, minor voiding complaints were observed. Other minor transient
      complications, defined as hematuria lasting >3 days, hematospermia, and rectal
      bleeding, occurred in 3.8%, 18.5%, and 9.1% of the patients, respectively. These
      complications were seen more often in patients with advanced tumor stage, younger
      age, and shorter duration of hormonal therapy. CONCLUSION: Transrectal gold
      marker implantation for high-precision prostate radiotherapy is a safe and well
      tolerated procedure.

PMID- 17512135
TI  - Antinociceptive effect and acute toxicity of the Hyptis suaveolens leaves aqueous
      extract on mice.
AB  - The aqueous extract of Hyptis suaveolens leaves was studied for their
      antinociceptive property in chemical and thermal models of nociception in mice.
      Oral administration of the aqueous extract (100, 200, and 400 mg/kg) dose
      dependently reduced the number of writhings induced by acetic acid, decreased the
      licking activity of the early phase in formalin test and increased the reaction
      time in hot-plate test. The antinociceptive effect was significantly antagonized
      by naloxone (3 mg/kg; i.p.). Preliminary acute toxicity study showed that no
      animal death with doses up to 5 g/kg (p.o.).

PMID- 17512136
TI  - Analgesic and antipyretic effects of Capparis zeylanica leaves.
AB  - The ethanol and water extracts of Capparis zeylanica leaves showed dose-dependent
      and significant (P<0.05) increases in pain threshold in tail-immersion test.
      Moreover, both the extracts (100-200 mg/kg) exhibited a dose-dependent inhibition
      of writhing and also showed a significant (P<0.001) inhibition of both phases of
      the formalin pain test. The water extract (200 mg/kg) significantly (P<0.01)
      reversed yeast-induced fever. Preliminary phytochemical screening of the extracts
      showed the presence of alkaloids, flavonoids, saponins glycosides, terpenoids,
      tannins, proteins and carbohydrates.

PMID- 17512137
TI  - [Management of pregnancies after adjustable gastric banding].
AB  - OBJECTIVES: To report our experience of the association adjustable gastric
      banding and pregnancy. To define a management for a such association. MATERIALS
      AND METHODS: Retrospective and descriptive study on two centers over a 3-year
      follow-up of pregnancies begun with a Lap-Band gastric banding placed by
      laparoscopic way. RESULTS: Twenty-one pregnancies, 22 newborns resulting from 18
      women were identified. Eleven patients were hospitalized. The motive of the
      hospitalization was severe epigastralgia for four patients requiring three
      deflations for mechanical complication. No case of preeclampsia was identified.
      Seven bands were deflated. In the group of the deflated bands, the mean maternal
      weight gain was 19 vs 10 kg (P=0.008), the mean birth weight was 3700 vs 3204 g
      (P=0.09) with a rate of fetal macrosomia increased, 50 vs 29% (P=0.038). The
      difference between the rates of cesarean delivery was not significant (NS)
      between the two groups. The childbirth term was appreciably the same, 39.4 vs
      38.6 weeks of gestation (NS). The only case of gestational diabetes was found in
      the deflated band group. Three intrauterine growth restrictions whose one fetal
      death occurred in the not deflated band group. CONCLUSION: Results obtained were
      comparable to those of the literature. This series confirms that adjustable
      gastric banding limits the usual complications of the morbid obesity during
      pregnancy. It is generally well tolerated and must not be thus deflated by
      principle, but only on symptoms. That will be a total dysphagia, severe
      epigastric pains, vomiting after the first trimester of pregnancy or an
      intrauterine growth restriction.

PMID- 17512138
TI  - Trends in non-medical use of anabolic steroids by U.S. college students: results
      from four national surveys.
AB  - This study assessed the prevalence, trends, and student- and college-level
      characteristics associated with the non-medical use of anabolic steroids (NMAS)
      among U.S. college students. Data were collected through self-administered mail
      surveys, from 15,282, 14,428, 13,953, and 10,904 randomly selected college
      students at the same 119 nationally representative colleges in 1993, 1997, 1999
      and 2001, respectively. The prevalence of lifetime, past-year and past-month NMAS
      was 1% or less and generally did not change significantly between 1993 and 2001,
      with one exception: past-year NMAS increased significantly among men from 1993
      (0.36%) to 2001 (0.90%). Multiple logistic regression analyses revealed that
      lifetime and past-year NMAS were associated with student-level characteristics
      such as being male and participation in intercollegiate athletics. Lifetime and
      past-year NMAS were also positively associated with several risky behaviors,
      including cigarette smoking, illicit drug use, drinking and driving, and DSM-IV
      alcohol use disorders. Nearly 7 out of every 10 lifetime non-medical users of
      anabolic steroids met past-year criteria for a DSM-IV alcohol use disorder.
      Although the overall prevalence of NMAS remained low between 1993 and 2001,
      findings suggest that continued monitoring is necessary because male student
      athletes are at heightened risk for NMAS and this behavior is associated with a
      wide range of risky health behaviors. The characteristics associated with NMAS
      have important implications for future practice and research.

PMID- 17512139
TI  - Development of a set of plasmid vectors for genetic manipulations of the
      pathogenic yeast Candida parapsilosis.
AB  - A system for genetic transformation of the yeast Candida parapsilosis, recently
      developed in our laboratory, opened a venue for investigation of this pathogenic
      species at the molecular level. In this study we extend the range of available
      experimental tools by construction of a genomic DNA library suitable for
      screening and isolation of genes by functional complementation of yeast mutants
      and a set of replicative plasmid vectors for genetic manipulation of C.
      parapsilosis cells. The plasmids are based on auxotrophic (CpGAL1, CpURA3,
      CpMET2, CpLYS4) and dominant (CaIMH3) selection markers. In addition, we
      constructed plasmid derivatives containing reporter genes yEGFP3 and KlLAC4
      coding for enhanced version of the green fluorescent protein and Kluyveromyces
      lactis beta-galactosidase, respectively. The vectors facilitate propagation and
      expression of cloned genes in C. parapsilosis cells and allow intracellular
      localization of gene products and/or monitoring the activity of promoter
      sequences.

PMID- 17512140
TI  - Hemocyanin from E. californicum encapsulated in silica gels: oxygen binding and
      conformational states.
AB  - Cooperativity depends on the existence of equilibria among functionally distinct
      conformational states that are affected by homo and heterotropic effectors. In
      order to isolate the quaternary conformations of hemocyanin from E. californicum,
      the 24-meric giant protein was encapsulated in wet, nanoporous silica gels,
      either in the absence or presence of oxygen. The deoxy- and oxy-hemocyanin gels
      exhibit a p50 for oxygen of 11 and 2.5 torr, respectively, values in close
      agreement with those for hemocyanin in solution. The observed Hill coefficients
      are lower than unity, indicating a conformational heterogeneity within each
      locked conformational state, a finding in agreement with the assumption that at
      least four conformational states are required to explain the oxygen binding
      properties of E. californicum hemocyanin in solution.

PMID- 17512141
TI  - Genomic characterization of Tv-ant-1, a Caenorhabditis elegans tag-61 homologue
      from the parasitic nematode Trichostrongylus vitrinus.
AB  - A full-length cDNA (Tv-ant-1) encoding an adenine nucleotide translocator (ANT or
      ADP/ATP translocase) (Tv-ANT-1) was isolated from Trichostrongylus vitrinus
      (order Strongylida), an economically important parasitic nematode of small
      ruminants. The uninterrupted open reading frame (ORF) of 894 nucleotides encoded
      a predicted protein of 297 amino acids, containing characteristic motifs [RRRMMM]
      and PX(D,E)XX(K,R). Comparison with selected sequences from the free-living
      nematode Caenorhabditis elegans, cattle and human showed that Tv-ANT-1 is
      relatively conserved. Sequence identity was the greatest in and near the
      consensus sequence RRRMMM, and in the six hydrophobic regions predicted to be
      associated with alpha-helices and to traverse the cell membrane. Phylogenetic
      analyses of selected amino acid sequence data, using the neighbor-joining and
      maximum parsimony methods, revealed Tv-ANT-1 to be most closely related to the
      molecule (Ce-ANT-3) inferred from the tag-61 gene of C. elegans. Comparison of
      the genomic organization of the full-length Tv-ant-1 gene was similar to that of
      tag-61. Analysis of the region (5'-UTR) upstream of Tv-ant-1 identified some
      promoter components, including GATA transcription factor, CAAT and E-box
      elements. Transcriptional analysis by reverse transcription polymerase chain
      reaction (RT-PCR) showed that Tv-ant-1 was transcribed in all developmental
      stages of T. vitrinus, including the first- to fourth- stage larvae (L(1)-L(4))
      as well as female and male adults. RNA interference, conducted by feeding C.
      elegans with double-stranded RNA (dsRNA) from Tv-ant-1 cDNA (using the homologous
      gene from C. elegans as a positive control), revealed no gene silencing. In spite
      of nucleotide identities of 100% in 23-30 bp stretches of sequence between the
      genes Tv-ant-1 and tag-61, these identities seem to be insufficient to achieve
      effective silencing in C. elegans using the parasite homologue/orthologue Tv-ant
      1. This first insight into an ANT of T. vitrinus provides a foundation for
      exploring its role in developmental and/or survival processes of trichostrongylid
      nematodes.

PMID- 17512142
TI  - Evolution of the interferon alpha gene family in eutherian mammals.
AB  - Interferon alpha (IFNA) genes code for proteins with important signaling roles
      during the innate immune response. Phylogenetically, IFNA family members in
      eutherians (placental mammals) cluster together in a species-specific manner
      except for closely related species (i.e. Homo sapiens and Pan troglodytes) where
      gene-specific clustering is evident. Previous research has been unable to clarify
      whether gene conversion or recent gene duplication accounts for gene-specific
      clustering, partly because the similarity of members of the IFNA family within
      species has made it historically difficult to identify the exact composition of
      IFNA gene families. IFNA gene families were fully characterized in recently
      available genomes from Canis familiaris, Macaca mulatta, P. troglodytes and
      Rattus norvegicus, and combined with previously characterized IFNA gene families
      from H. sapiens and Mus musculus, for the analysis of both whole and partial gene
      conversion events using a variety of statistical methods. Gene conversion was
      inferred in every eutherian species analyzed and comparison of the IFNA gene
      family locus between primate species revealed independent gene duplication in M.
      mulatta. Thus, both gene conversion and gene duplication have shaped the
      evolution of the IFNA gene family in eutherian species. Scenarios may be
      envisaged whereby the increased production of a specific IFN-alpha protein would
      be beneficial against a particular pathogenic infection. Gene conversion, similar
      to duplication, provides a mechanism by which the protein product of a specific
      IFNA gene can be increased.

PMID- 17512143
TI  - Characterization of an H5N1 avian influenza virus from Taiwan.
AB  - In 2003, an avian influenza (AI) virus of H5N1 subtype (A/Duck/China/E319-2/03;
      Dk/CHN/E319-2/03) was isolated from a smuggled duck in Kinmen Island of Taiwan.
      Phylogenetic analysis and pairwise comparison of nucleotide and amino acid
      sequences revealed that the virus displayed high similarity to the H5N1 viruses
      circulating in Asia during 2004 and 2005. The hemagglutinin (HA) protein of the
      virus contained multiple basic amino acid residues (-RERRRKR-) adjacent to the
      cleavage site between the HA1 and HA2 domains, showing the highly pathogenic (HP)
      characteristics. The HP phenotype was confirmed by experimental infection of
      chickens, which led up to 100% mortality within 24-72h postinfection. The virus
      replicated equally well in the majority of organs of the infected chickens with
      titers ranging from 10(7.5) to 10(4.7) 50% embryo lethal dose (ELD50) per gram of
      tissue. In a mouse model the virus exhibits low pathogenic characteristics with a
      lethal infection observed only after applying high inoculating dose (>or=10(7.6)
      ELD50) of the virus. The infectious virus particles were recovered only from the
      pulmonary system including trachea and lungs. Our study suggests that ducks
      infected with H5N1 AIV of HPAI pathotype showing no disease signs can carry the
      virus silently and that bird smuggling represent a serious risk for H5N1 HPAI
      transmission.

PMID- 17512144
TI  - Environmental mycobacteria in soil and water on beef ranches: association between
      presence of cultivable mycobacteria and soil and water physicochemical
      characteristics.
AB  - Exposure to environmental mycobacteria has been reported to be a factor
      contributing to false-positive results on bovine serological tests detecting
      antibodies to Mycobacterium avium subsp. paratuberculosis (Mptb). This study was
      conducted to investigate the association between recovery of mycobacteria from
      the environment of cattle and both (i) historically high or low seroprevalence to
      Mptb, and (ii) soil and water physicochemical characteristics. Eighty-two samples
      (soil and water) from nine beef cattle ranches in South-central and South Texas
      were assessed for the presence of mycobacteria. Twelve mycobacterial species were
      cultured from soil and water from four herds; no Mptb were detected in
      environmental samples. A positive culture of environmental mycobacteria from soil
      was significantly associated with lower pH and calcium as well as higher iron,
      zinc and manganese contents. Beef cattle are likely to be exposed to
      environmental mycobacteria that may contribute to false-positive results on
      ELISAs for Mptb infection. Exposure rates to these mycobacteria likely vary
      across small geographical areas and may be related to soil and/or water
      physicochemistry.

PMID- 17512145
TI  - Correlation of nitric oxide (NO) activity and gonadal function in Japanese quail,
      Coturnix coturnix japonica following temporal phase relation of serotonergic and
      dopaminergic oscillations.
AB  - Nitric oxide (NO), a highly reactive and short-lived radical, is considered to be
      an important trigger molecule for several physiological mechanisms including
      gonadotrophin releasing hormone (GnRH) secretion in mammals, although there is no
      such information in avian literature. On the other hand, specific temporal phase
      relation of circadian neural (serotonergic and dopaminergic) oscillations is
      reported to modulate reproductive activity in many avian species including
      Japanese quail. The present study was undertaken to investigate the correlation
      of NO activity and gonadal function of Japanese quail. In experiment I, the
      effect of serotonin and dopamine precursors, (5-hydroxytryptophan (5-HTP) and L
      dihydroxyphenyalanine (L-DOPA) respectively; 5 mg per 100g body weight)
      administered at intervals of 8 or 12h over a period of 13 days, was studied on
      reproductive responses and NO activity. Measurements of body weight, cloacal
      gland size, testosterone concentration, spermatogenesis, nitrite-nitrate
      concentration in plasma, hypothalamus and testes, and NADPH-diaphorase (NADPH-d)
      activity in testes were made on the 2nd, 3rd, 6th and 11th days of treatment and
      2nd and 30th day post-treatment. In experiment II, quail were divided into five
      groups including the control. One experimental group received 13 daily injections
      of 5-HTP and L-DOPA at intervals of 8h along with 0.1 ml of normal saline
      administered orally (8-hr+Veh), while another group of 8-hr quail received NO
      donor (sodium nitroprusside (SNP), 5 mg per 100 g body weight) orally (8-hr+SNP).
      The third experimental group received 5-HTP and L-DOPA at intervals of 12h along
      with normal saline (12-hr+Veh), while the fourth group of quail along with 5-HTP
      and L-DOPA at intervals of 12h also received the NOS inhibitor (N-nitro-L
      arginine methyl ester, L-NAME, 25 microg per 100 g body weight) intraperitoneally
      (12-hr+L-NAME) for 13 days. This experiment was terminated after 21 days of the
      treatment. Results indicate that 5-HTP and L-DOPA administered 8h apart (8-hr)
      suppressed but if given 12h apart (12-hr) stimulated the reproductive system and
      NO activity compared to the control. These effects were apparent on the 6th day
      of injections and were maintained 30 days following the termination of the
      treatment. A significant decrease in nitrite and nitrate concentration and NADPH
      d activity in reproductively inhibited 8-hr group and an increase in
      reproductively stimulated 12-hr quail was also evident. In contrast, these
      activities were stimulated in 8-hr+SNP quail and were suppressed in 12-hr+L-NAME
      group quail. It is concluded that activity of the reproductive system and NO
      activity waxes and wanes simultaneously in Japanese quail. Moreover, experimental
      modulation of gonadal activity (following changes in the phase relation of
      serotonergic and dopaminergic activity) or NO activity (following the
      administration of NO modulator or inhibitor) affects each other maintaining a
      parallel relation between the two systems. Further, it is interesting to note
      that the gonado-stimulatory effect of SNP overpowers the gonado-inhibitory
      effects of the 8-hr time interval and inhibitory effects of L-NAME mask the
      stimulatory effects of 12-hr temporal relation of 5-HTP and L-DOPA
      administration. These findings strongly suggest that reproductive effects may be
      induced via changes in NO activity, however the exact mechanism by which NO
      drives gonadal axis needs to be ascertained.

PMID- 17512146
TI  - Xenografting of adult mammalian testis tissue.
AB  - Xenografting of testis tissue from immature males from several mammalian species
      to immunodeficient mouse hosts results in production of fertilization-competent
      sperm. However, the efficiency of testis tissue xenografting from adult donors
      has not been critically evaluated. Testis tissue xenografting from sexually
      mature animals could provide an option to preserve the genetic material from
      valuable males when semen for cryopreservation cannot be collected. To assess the
      potential use of this technique for adult individuals, testes from adult animals
      of six species (pig, goat, cattle, donkey, horse and rhesus monkey) were
      ectopically grafted to host mice. Grafts were recovered and analyzed at three
      time points: less than 12 weeks, between 12 and 24 weeks and more than 24 weeks
      after grafting. Histological analysis of the grafts revealed effects of species
      and donor tissue maturity: all grafts from species with greater daily sperm
      production (pig and goat) were found to have degenerated tubules or grafts were
      completely degenerated. None of the xenografts from mature adult bull and monkeys
      contained differentiated spermatogenic cells when examined more than 12 weeks
      post-grafting but tubules with Sertoli cells only remained. In grafts from a
      young adult bull, Sertoli cells persisted much longer than with the mature adult
      grafts. In grafts from a young adult horse, spermatogenesis proceeded to meiosis.
      In grafts from a young adult donkey and monkey, however, complete spermatogenesis
      was found in the grafts. These results show that testis tissue grafts from mature
      adult donors did not support germ cell differentiation but seminiferous tubules
      with Sertoli cells only survived in some species. The timing and progression of
      tubular degeneration after grafting of adult testis tissue appear to be related
      to the intensity of spermatogenesis at the time of grafting. Testis tissue from
      sub-adult donors survives better as xenograft than tissue from mature adult
      donors, and complete spermatogenesis can occur albeit with species-specific
      differences.

PMID- 17512147
TI  - In vitro and in vivo sustained-release characteristics of theophylline matrix
      tablets and novel cluster tablets.
AB  - We compared the in vitro/in vivo properties of theophylline between two sustained
      release preparations, which are administered once a day. Tablet A is a
      swelling/disintegration-type matrix tablet consisting of hydrophobic wax granules
      and hydrophilic polymer granules (cluster tablets). Tablet B is a matrix tablet
      consisting of hydrophilic polymer granules. We conducted a dissolution test with
      JPXIV in vitro, and compared the results between the two preparations. Neither pH
      nor agitation intensity influenced these preparations. After they were immersed
      in oleic acid, there were no marked changes in the dissolution properties in the
      dissolution test. After administration of Tablets A and B containing theophylline
      at 200mg to fasted dogs, we compared plasma level profiles of theophylline. The
      mean plasma level of theophylline gradually increased to a maximum
      (7.17microg/mL) 4h after administration of Tablet A. After administration of
      Tablet B, a similar finding was noted, with a maximum of 6.09microg/mL. Tablet B
      showed a higher coefficient of variation (CV) for the plasma level at each point.
      Subsequently, we administered two tablets of preparations A and B containing
      theophylline at 200mg to healthy volunteers who had not been fasted, and compared
      plasma level concentration of theophylline. The mean plasma level of theophylline
      gradually increased to a maximum (6.09microg/mL) 12h after administration of
      Tablet A, but then decreased, with a half-life of 9.10h. After administration of
      Tablet B, a similar finding was noted, with a maximum of 7.87microg/mL and a half
      life of 7.76h. Tablet A showed a significantly higher plasma concentration 1 and
      2h after administration; however, there were no significant differences at other
      points. The C(max) of Tablet B was significantly higher than that of Tablet A.
      However, there were no significant differences in other pharmacokinetic
      parameters between the two preparations. The T(max) of Tablet A was 10-12h after
      administration, relatively constant. However, that of Tablet B was 10-18h after
      administration. The CV for T(max) was 9.8% for Tablet A and 22.0% for Tablet B.
      After administration of Tablet B, the plasma level of theophylline varied at each
      point. Based on these results, inter-subject variations after administration of
      Tablet A may be less marked than those after administration of Tablet B. It is
      concluded that, the cluster tablets A developed in this study showed
      significantly less inter-subject variation of theophylline plasma levels than the
      conventional matrix tablets B.

PMID- 17512148
TI  - [Role of biological assays in the diagnosis of Lyme borreliosis presentations.
      What are the techniques and which are currently available?].
AB  - The biological diagnosis of Borrelia burgdorferi sensu lato infection is usually
      made by antibody detection in patient sera. Thus, serological testing (Elisa,
      immunoblotting) is essential for a biological diagnosis. Specific antibody
      detection is usually done in serum and CSF of patients suspected of Lyme
      borreliosis. Laboratories must follow European recommendations to validate these
      assays in routine practice. Antibody detection lacks sensitivity in the early
      cutaneous phase of the infection. Therefore, serological testing is not
      recommended for the diagnosis of erythema migrans. The interpretation of serology
      must take into account the variability of Elisa sensitivity and specificity and
      the lack of standardization for Western-blotting in Europe. Besides these
      indirect diagnosis techniques, there is also direct detection of spirochetes by
      culture or by in vitro DNA amplification but these require adequate samples.
      These molecular tests must not be performed routinely, but only for specific
      clinical situations and in specialized laboratories only.

PMID- 17512149
TI  - [Management of accidental exposure to blood in the Treichville teaching hospital,
      Abidjan (Cote-d'Ivoire)].
AB  - OBJECTIVE: The aim of this study was to assess care and preventive measures for
      accidental exposure to blood (AEB) in Abidjan. METHODS: A retrospective study of
      all AEB reported in the Infectious and Tropical Diseases Center of the
      Treichville University Hospital was made between January 2000 and December 2005.
      Epidemiology, management, clinical and biological post-exposure follow-up were
      analyzed. RESULTS: One hundred eighty-two AEB were managed over 6 years (151
      needlesticks, 14 ocular projections of blood, 12 cuts, and 5 mucocutaneous
      exposure to blood). 94 men (51.6%) and 68 women (48.4%) were included [sex ratio
      1.4] mean age 33.8 years+/-7.4 years. Physicians (29.1%), nurses (19.8%),
      assistant nurse (12.1%), and medical students (11.4%) were the professional
      categories which declared most accidents. Among them, only 51.1% was correctly
      vaccinated against hepatitis B. The average delay of consultation was 26.5 hours
      (1-240 hours), and 82.9% of victims consulted before the 48th hour.
      Antiretroviral prophylaxis was prescribed to 151 patients among whom 45% with
      bitherapy (Zidovudine and Lamivudine), and 55% with HAART including an
      antiprotease. Only 60 patients had one actual month of treatment. Despite the
      weak follow-up, no case of HIV seroconversion was reported 6 month after
      exposure. CONCLUSION: This work underlines once again the high frequency of AEB
      in Abidjan despite a under reporting, and calls for the implementation of a
      policy to train health care workers on AEB preventive measures.

PMID- 17512150
TI  - [Mucocutaneous leishmaniasis in Brazilian Amazonia].
AB  - BACKGROUND: This study had for aim to describe the clinical aspects and favoring
      factors of mucosal Leishmaniasis in an Amazonian population of 30,000 habitants
      in Guajara-Mirim (Rondonia-Brazil). MATERIAL AND METHOD: A descriptive study was
      made of 16 patients with mucosal Leishmaniasis among 170 patients infected by
      Leishmania. Inclusion criteria were a mucosal lesion and positivity of direct
      microscopic examination. The patients were investigated retrospectively. RESULTS:
      Patients with mucosal Leishmaniasis were young and mostly male The absence of
      treatment and the number of cutaneous lesions were probably responsible for the
      mucosal form, as well as the host immune response and maybe, the parasite species
      or vector characteristics. CONCLUSION: The mucosal form of leishmaniasis affects
      more often young male patients and this form must be detected early to avoid
      destructing lesions.

PMID- 17512151
TI  - [Endothelial progenitor cells: new biomarkers and potential therapy in intensive
      care].
AB  - One of the most important breakthroughs in the field of vascular biology in the
      last decade was the discovery of endothelial progenitor cells (EPCs). These
      angiogenic cells dwell in bone marrow, and may be found in the general
      circulation spontaneously or in response to various stimuli such as ischemia,
      growth factor, pro-inflammatory cytokines, and drugs such as statins. There is
      growing evidence that EPCs can differentiate into mature endothelial cells and
      facilitate endothelial repair and angiogenesis in vivo. In recent years,
      consistent publications have shown that EPCs provide both diagnostic and
      prognostic information with respect to cardiovascular diseases, acute lung
      injury, and sepsis. Activation of EPCs from the bone marrow or injection of these
      cells may be used as a therapeutic option for the treatment of ischemic
      cardiovascular diseases.

PMID- 17512152
TI  - [Factors associated with mortality in Legionnaires' disease, France, 2002-2004].
AB  - Risk factors for Legionnaires' disease are well known (older age, smoking, or
      immunosuppression), however, the factors associated with mortality are less
      documented. A retrospective analysis based on cases notified between 2002 and
      2004 was conducted in France to identify these factors. METHOD: Cases were
      identified through mandatory notifications sent to the Institut de veille
      sanitaire, France. Factors associated with mortality were identified using a
      logistic regression analysis. RESULTS: Three thousand two hundred sixty-seven
      cases of Legionnaire's disease were notified during the study period and the
      evolution was documented for 85% of the cases (2.791). Three hundred seventy
      seven deaths (13.5%) were notified. 72.5% of the patients were men and the median
      age was 61. The multivariate analysis applied to patients under 60 years revealed
      that cancer or hemopathy (OR=6.4 CI95% 3.6-11.2), underlying renal disease
      (OR=3.2 CI95% 1.0-9.9), or alcohol abuse (OR=2.2 CI95% 1.1-4.4) were associated
      with mortality. For older patients (>60 years) factors linked to mortality were:
      cancer/hemopathy (OR=1.8 CI95% 1.2-2.6), underlying renal disease (OR=3 CI95% 1.4
      6.4), underlying cardiac disease (OR=2.4 CI95% 1.4-4), alcohol abuse (OR=2.4
      CI95% 1.2-5.2), immunosuppression (OR=1.7 CI95% 1.1-2.6), nosocomial acquisition
      of the disease (OR=2.0 CI95% 1.3-3), or infection acquired in nursing home
      residents (OR=2.4 IC 95% 1.6-3.6). CONCLUSION: These preliminary results further
      describe Legionnaires' disease and its mortality. However, they should be
      confirmed by carefully conducted prospective analysis. The description of LD
      patients at high risk of death will contribute to better prevention measures.

PMID- 17512153
TI  - Effect of a caloric restriction regimen on the angiogenic capacity of aorta and
      on the expression of endothelin-1 during ageing.
AB  - Ageing is accompanied by impaired angiogenesis, as well as by a deficient
      expression of several angiogenic growth factors and the alteration of endothelial
      functions. Caloric restriction (CR) is the only intervention that can extend
      lifespan and retard age-related-decline functions in mammals by reducing the rate
      of ageing and the progression of the associated diseases. Herein, we have
      investigated the effects of ageing and of a caloric restriction regimen (mild or
      severe) on the angiogenic response and on the expression of endothelin-1 (ET-1)
      in the aorta of male 3-, 12- or 24-month-old Sprague-Dawley rats fed ad libitum
      (AL), fed ad libitum and fasted 1 day a week (mild CR) or fasted every other in
      alternate days (severe CR). Our findings, using the rat aorta ring assay, show
      that the angiogenic capacity of aorta decreases with ageing in the oldest rats
      only. Furthermore, caloric restriction counteracts the age-related changes
      caloric restrictions actually give raise to a similar recovery. Interestingly,
      the mRNA ET-1 levels as well as ET-1 expression in aorta sprouting decreases both
      in middle and in aged animals. Mild and severe caloric restriction regimens
      prevents ET-1 changes.

PMID- 17512154
TI  - Comparison of the probability of target attainment between ceftriaxone and
      cefepime in the cerebrospinal fluid and serum against Streptococcus pneumoniae.
AB  - Although the disposition of ceftriaxone and cefepime in the cerebrospinal fluid
      (CSF) has been described, the ability of these agents to achieve critical
      pharmacodynamic targets against Streptococcus pneumoniae in CSF has not been
      reported. Plasma and CSF pharmacokinetic data were obtained from hospital
      patients with external ventricular drains and receiving ceftriaxone or cefepime.
      Concentration-time profiles in plasma and CSF were modeled using a 3-compartment
      model with 0-order infusion and 1st-order elimination and transfer. The model
      parameters were identified with population pharmacokinetic analysis (Big Non
      Parametric Adaptive Grid with adaptive gamma). A Monte Carlo Simulation (9999
      subjects) estimated the probability of target attainment (PTA) for total drug CSF
      concentrations at 50% and 100% T>MIC for ceftriaxone 2G IV Q12H and cefepime 2G
      IV Q8H. The S. pneumoniae bloodstream infection isolates from the SENTRY
      Antimicrobial Surveillance Program (USA) provided the distribution of
      contemporary (2003-2004) MICs. Post-Bayesian measures of bias and precision,
      observed-predicted plots, and R2 values were highly acceptable for both drugs.
      The probabilities of achieving 50% and 100% T>MIC in the CSF for ceftriaxone were
      76% and 65%, respectively. For cefepime, the PTA at 50% and 100% T>MIC in the CSF
      were 91.8% and 82%, respectively. The CSF pharmacodynamics against S. pneumoniae
      for cefepime were superior to that of ceftriaxone. The implications of these
      findings need to be reexamined in the clinical setting.

PMID- 17512155
TI  - Synthetic genes: a tool for identifying human papillomavirus genotypes by
      hybridization and polymerase chain reaction-based assays.
AB  - Obtaining positive polymerase chain reaction (PCR) controls for human
      papillomavirus (HPV) diagnostic tests has been difficult because of prevalence
      variation in different geographic regions of each high-risk viral type.
      Overlapping oligonucleotides were designed for HPV-18, HPV-31, HPV-45, and HPV-58
      type-specific (TS) sequences. Synthetic HPV viral genes were constructed by 2
      step assembly PCR for accurately diagnosing TS HPV infection.

PMID- 17512156
TI  - Toward cost-effective initial care for substance-abusing homeless.
AB  - In a randomized controlled trial, behavioral day treatment, including contingency
      management (CM+), was compared to contingency management components alone (CM).
      All 206 cocaine-dependent homeless participants received a furnished apartment
      with food and work training/employment contingent on drug-negative urine tests.
      CM+ also received cognitive-behavioral therapy, therapeutic goal management, and
      other intervention components. Results revealed that CM+ treatment attendance and
      abstinence were not significantly different from CM during 24 weeks of treatment.
      After treatment and contingencies ended, however, CM+ showed more abstinence than
      CM, indicating a delayed effect of treatment from 6 to 18 months. CM+ had more
      consecutive weeks abstinent across 52 weeks, but not during active treatment. We
      conclude that CM alone may be viable as initial care for cocaine-dependent
      homeless persons. That CM+ yields more durable abstinence indicates that it may
      be appropriate as stepped-up care for clients not responding to CM (Clinical
      Trials.gov, no. NCT00368524).

PMID- 17512157
TI  - Utility of sweat patch testing for drug use monitoring in outpatient treatment
      for opiate dependence.
AB  - We evaluated the utility of sweat testing for monitoring of drug use in
      outpatient clinical settings and compared sweat toxicology with urine toxicology
      and self-reported drug use during a randomized clinical trial of the efficacy of
      buprenorphine for treatment of opioid dependence in primary care settings. All
      study participants (N = 63) were opiate-dependent, treatment-seeking volunteers.
      The results based on toxicology tests obtained from 188 properly worn and
      unadulterated patches (out of 536 applied) show that the level of agreement
      between positive sweat test results and positive urine results was 33% for
      opiates and 92% for cocaine. The findings of this study, that there is a low
      acceptability of sweat patch testing by patients (only 54.3% were brought back
      attached to the skin) and that weekly sweat testing is less sensitive than weekly
      urine testing in detecting opiate use, suggest limited utility of sweat patch
      testing in outpatient clinical settings.

PMID- 17512158
TI  - Community reinforcement approach plus vouchers for cocaine dependence in a
      community setting in Spain: six-month outcomes.
AB  - The aim of this study was to assess the efficacy of the community reinforcement
      approach (CRA) plus vouchers treatment in achieving cocaine abstinence and
      treatment retention among patients enrolled in an outpatient program for cocaine
      dependence in Spain. Forty-three patients were randomly assigned to one of two
      treatment conditions in a community setting: CRA plus vouchers or standard care.
      Of the patients who received the CRA plus vouchers program, 73% completed 24
      weeks of treatment, as compared with 42% of the patients who received standard
      care who did. In the CRA plus vouchers group, 40% of the patients achieved 24
      weeks of continuous cocaine abstinence, as compared with 21% of the patients in
      the standard care group who did. These results support the effectiveness and
      generalizability of the CRA plus vouchers treatment in a community setting
      outside of the United States. Further follow-up is required to confirm the long
      term maintenance of the results.

PMID- 17512159
TI  - Individual and system influences on waiting time for substance abuse treatment.
AB  - Waiting time is a contemporary reality of many drug abuse treatment programs,
      resulting in substantial problems for substance users and society. Individual and
      system factors that influence waiting time are diverse and may vary at different
      points in the treatment continuum. This study assessed waiting time preceding
      clinical assessment at a centralized intake unit and during the period after the
      assessment but before treatment entry. The present study included 577 substance
      abusers who were enrolled in a large clinical trial of two brief treatment
      interventions in a midsize metropolitan area in Ohio. Bivariate analyses
      identified individual and system factors that influenced preassessment and
      postassessment waiting time, as well as total wait to treatment services.
      Multivariate analyses demonstrated that longer wait time for an assessment is
      influenced by being court referred, less belief in having a substance abuse
      problem, and less desire for change. A shorter wait to actually enter treatment
      is predicted by having a case manager, being more ready for treatment, and having
      less severe employment and alcohol problems. The different influences present
      during the two waiting periods suggest that assessment and treatment programs
      need to implement system changes and entry enhancement interventions that are
      specific to the needs of substance abusers at each waiting period.

PMID- 17512160
TI  - Perioperative sargramostim (recombinant human GM-CSF) induces an increase in the
      level of soluble VEGFR1 in colon cancer patients undergoing minimally invasive
      surgery.
AB  - INTRODUCTION: Experimentally, laparotomy is associated with increased tumor
      growth. In humans, abdominal surgery is associated with immunosuppression and
      elevated plasma VEGF levels that might stimulate tumor growth early after
      surgery. Avoidance of these surgery-related changes and their consequences may be
      advantageous. Granulocyte-macrophage colony stimulating factor (GMCSF) is a non
      specific immune system up-regulator that has also been associated,
      experimentally, with increased release of soluble VEGF Receptor 1 (sVEGFR1) which
      is an endogenous inhibitor of VEGF. This study's purpose was to determine the
      impact of perioperatively administered recombinant human GMCSF (rhu-GMCSF) on
      both immune function and plasma sVEGFR1 levels in colorectal cancer patients.
      METHODS: This randomized placebo-controlled study included 36 colorectal cancer
      patients who underwent minimally invasive resection (17 GMCSF, 19 Placebo).
      Patients received 7 subcutaneous injections of either rhu-GMCSF, 125 microg/m2,
      or saline on preoperative days 3, 2 and 1 and on postoperative days (POD) 1, 2, 3
      and 4. A number of immune parameters were followed and plasma levels of soluble
      VEGF Receptor 1 (sVEGFR1) and VEGF were determined. RESULTS: The total WBC,
      neutrophil, eosinophil, and monocyte counts were significantly higher after
      surgery in the GMCSF group; no differences were noted for the other immune
      parameters. In the GMCSF group, median plasma sVEGFR1 levels were significantly
      elevated on POD 1 (188.1 pg/ml), and on POD 5 (142.8 pg/ml) when compared to pre
      GMCSF levels (0 pg/ml) (p-value<0.05 for all comparisons). In the placebo group,
      the POD5 median sVEGFR1 level (116.3 pg/ml) was elevated and of borderline
      significance (p=0.05) vs the pre-treatment result (0 pg/ml). Of note, both groups
      had significantly elevated median plasma VEGF levels on POD 5 (Control 435.7
      pg/ml; GMCSF 385.3 pg/ml) when compared to their preoperative results (Control
      183.3 pg/ml, p=0.0013; GMCSF 171.5 pg/ml, p=0.0055). CONCLUSIONS: Perioperative
      GMCSF was not associated with an immune function benefit in this study, however,
      such treatment leads to increased plasma sVEGFR1 levels. Colorectal resection,
      with or without GMCSF, was also associated with increased VEGF levels
      postoperatively. Increased plasma levels of sVEGFR1 after surgery might limit the
      pro-angiogenic tumor stimulatory effects of VEGF. Further study of GMCSF's impact
      on angiogenesis appears warranted.

PMID- 17512161
TI  - Environmental stress factors affecting survival and virulence of Campylobacter
      jejuni.
AB  - Enteric pathogens are constantly exposed to stressful conditions in their natural
      habitat in the host and even more in the extra-host environment, including food
      processing. The aim of this study was to evaluate the effect of selected
      environmental stress factors: temperature shift, starvation and atmospheric
      oxygen concentration on culturability/viability of two Campylobacter jejuni
      isolates. Additionally, after stress exposure, in an in vitro cell culture model
      using Caco-2 cells, the adhesion, invasion and intracellular survival of C.
      jejuni were studied. Nutrient insufficiency was the most powerful stress factor
      which significantly affected C. jejuni culturability and viability, as well as,
      adhesion and invasion properties. Temperature elevation induced a transient
      growth arrest, and temporary loss of pathogenic potential as indicated by
      impaired adhesion and invasion efficiency of C. jejuni. However, bacteria
      recovered within 24-48h inside the Caco-2 cells. Oxidative stress neither
      affected C. jejuni growth nor reduced the binding and invasion into Caco-2 cells.
      Only 5h oxygen exposure increased the invasion capability and intraepithelial
      survival of the clinical isolate. Modulation of C. jejuni virulence in response
      to environmental stress factors may have further implications in the pathogenesis
      of campylobacteriosis.

PMID- 17512162
TI  - Effects of thoracic and hiatal clamping in repair of ruptured abdominal aortic
      aneurysms.
AB  - The purpose of this study was to determine the effects of hiatal and thoracic
      clamping on postoperative outcome and morbidity and factors affecting mortality
      and morbidity. The records of 102 patients who had undergone ruptured abdominal
      aortic aneurysm repair between 1993 and 2005 were evaluated retrospectively.
      Hiatal clamping and thoracic clamping were performed in 72 patients and 30
      patients, respectively. Postoperative complications and survival were evaluated
      comparatively between the two groups by univariate and multivariate statistical
      analyses. Overall mortality and hospital mortality rates were 63 (61.8%) and 24
      (23.5%) patients, respectively; and there was no difference between the two
      groups. Postoperative respiratory complications, gastrointestinal complications,
      and blood requirement were higher in the thoracic clamping group. Preoperative
      shock and renal ischemia time (>30 min) were found to be significant predictors
      of hospital mortality. Postoperative renal failure was the only independent
      postoperative predictor of mortality. In the follow-up period, cardiac event was
      an independent predictor of late mortality. If hospital mortalities were
      excluded, 5-year and 10-year cumulative survivals were 57.82 +/- 5.85% and 38.16
      +/- 6.97%, respectively. Cross-clamp level did not have a significant effect on
      long-term survival. Although both thoracic and hiatal clamping had no effect on
      mortality, postoperative respiratory complications, blood requirement, and
      intestinal ischemia were more pronounced in patients operated with thoracic
      clamping. Hiatal clamping is preferable for a safe postoperative period.

PMID- 17512163
TI  - Echo-sclerosis hemodynamic conservative: a new technique for varicose vein
      treatment.
AB  - Treatment of venous insufficiency has been revolutionized by introduction of
      various less invasive procedures. The echo-sclerosis hemodynamic conservative
      (ESEC) technique is a completely new treatment of varicose veins that combines
      ultrasound-monitored sclerosis, innovative sclerotherapy findings, and
      hemodynamic principles. The objective of venous stasis suppression is achieved by
      the ESEC technique through a conservative and functional approach that preserves
      venous drainage and saphenous vessel integrity. The technique is efficient,
      simple, safe, in-office manageable, and easily repeatable, although it obviously
      requires training and skill. It may be considered as the primary treatment for
      most varicose patients. Evaluation of long-term results, with regard to
      comparison with other techniques, should assess cost efficacy from a lifelong
      point of view.

PMID- 17512164
TI  - The management of Takayasu's arteritis: personal experience.
AB  - Takayasu's arteritis is a chronic vasculitis mainly involving the aorta and its
      main branches. Almost all patients have ischemic disorders of the involved
      vessels. Treatment is nowadays controversial. Relapses are frequent. In the
      present study, we elucidate the long-term outcomes of our patients with
      Takayasu's arteritis. Between November 1993 and October 2003, 10 patients with
      Takayasu's disease were treated. All patients underwent medical treatment
      (corticosteroid for 7 months, cyclophosphamide for 3 months, and methotrexate for
      12 months). Two patients stopped treatment with methotrexate when renal failure
      occurred. Four patients underwent a surgical procedure. During treatment,
      erythrocyte sedimentation rate and C-reactive protein concentrations were
      determined as indexes of inflammatory activity and treatment responsiveness. Four
      out of eight patients (50%) who underwent the full treatment with methotrexate
      had no relapse of the disease. The other four patients (50%) had relapse of the
      disease but had a better response to new corticosteroid treatment. The two
      patients who stopped methotrexate treatment died from complications of Takayasu's
      arteritis. In our personal experience, long-term treatment with methotrexate
      demonstrated a certain efficacy in avoiding relapse, maintaining stability of
      results, and amplifying the effects of steroid in patients with relapse.

PMID- 17512165
TI  - Epidemiology and long-term prognostic factors in acute type B aortic dissection.
AB  - The epidemiological data and reports on long-term predictors of mortality after
      medically or endovascularly and medically treated patients with acute type B
      aortic dissection (AD) are scarce. Patients with type B AD between 2000 and 2004
      were identified through the inpatient endovascular or autopsy registry at Malmo
      Lund University Hospital, Sweden. Seventy-two patients had acute type B AD, of
      whom eight were found at autopsy. Shock due to ruptured type B AD was associated
      with in-hospital mortality (P = 0.006) in the 64 eligible patients. Renal
      insufficiency (odds ratio [OR] = 4.7, 95% confidence interval [CI] 1.1-19.4) and
      coexistent aortic disease (OR = 4.1, 95% CI 1.0-16.9) remained as independent
      predictors for long-term mortality after multivariate logistic regression
      analysis. Endovascular intervention (n = 32) was associated with neither short-
      nor long-term mortality. The estimated overall incidence of acute type B AD was
      2.1/100,000 person-years, and the highest incidence rates were found in men aged
      65-74 years (14.6/100,000 person-years) and women aged 75-84 years (19.0/100,000
      person-years). Survival in patients with complicated acute type B AD managed with
      the endovascular technique was the same as in uncomplicated medically treated
      patients. Renal insufficiency and coexistent aortic disease were strong
      predictors for long-term mortality.

PMID- 17512166
TI  - Abdominal aortic aneurysm surgery in a district general hospital: a 15-years
      experience.
AB  - The incidence of patients presenting with both ruptured abdominal aortic aneurysm
      (RAAA) and elective abdominal aortic aneurysm (EAAA) increases with age. The aim
      of our study was to find out the incidence of RAAA, age and sex groups of
      patients at risk, and 30-day all-cause perioperative mortality associated with
      RAAA as well as EAAA repair in a busy district general hospital over a 15-year
      time period. All patients operated for AAA during 1989-2003, both elective and
      ruptured, were included in the study. Patients who died in the community from
      RAAA were also included. The data were collected from the hospital information
      system, theater logbooks, intensive therapy unit records, postmortem register,
      and patients' medical notes. We divided the data for RAAA into two groups of 7.5
      years each to see if there was any improvement over time in 30-day postoperative
      mortality. There were 816 cases of AAA, which included 468 RAAAs (57%) and 348
      EAAAs (43%). Out of 468 RAAAs, 243 patients had emergency repair, of whom 213
      were males. There were 201 patients who had RAAA postmortem (43%). Median age
      (range) was 73 (54-94) years in males and 77 (52-99) years in females, with a
      male-to-female ratio of 7:1. The peak incidence of RAAA was over 60 years of age
      in males and 70 years in females. Incidence of RAAA was 7.3/100,000/year in males
      and 5/100,000/year in females. For RAAA, 30-day perioperative mortality was 43%
      (105/243) while overall mortality was 70% (330/468), which includes deaths in the
      community. There was no improvement in 30-day mortality over time after comparing
      data for the first 7.5 years (50/115, 43.5%) with those for the second set of 7.5
      years (55/128, 43%). There were 348 patients who had EAAA repair over the same
      period, comprising 282 males, with a male:female ratio of 4.3:1. The 30-day
      mortality in the elective group was 7.75%. Incidence and mortality of RAAA remain
      high. A high proportion of patients with AAA remain undiagnosed and die in the
      community. More lives may be saved if a screening program is started for AAA.

PMID- 17512167
TI  - The effect of observing response procedures on the reduction of over-selectivity
      in a match to sample task: immediate but not long term benefits.
AB  - Stimulus over-selectivity occurs when only one of potentially many aspects of the
      environment comes to control behavior. In three experiments, adult participants
      with no developmental disabilities were trained and tested in a match to samples
      (MTS) paradigm. Participants in Experiment 1 were assigned to one of two
      conditions, which differed on whether an observing response procedure was in
      place. Findings indicated that an MTS procedure can induce over-selectivity in
      this population if a time delay is included between sample and comparison. Over
      selectivity emerged significantly more in the group who did not use an observing
      response procedure. In Experiments 2 and 3, participants were exposed to a re
      test phase, in which the initial stimuli were presented again, but without the
      use of an observing response in either group. The observing response procedure
      only reduced over-selectivity when in place, but performance did not remain high
      following its withdrawal. This effect was noted regardless of the type of
      observing response procedure used (pointing versus naming). These findings
      suggest that an observing response procedure may be effective in reducing over
      selectivity, however, these effects do not last post intervention, and that this
      may limit the clinical usefulness of the technique.

PMID- 17512168
TI  - Attitudes of children with dysphonia.
AB  - SUMMARY: Because voice disorders in childhood may have a negative impact on
      communicative effectiveness, social development, and self-esteem, the objective
      was to determine the impact of voice disorders on lives of children from the
      perspective of chronically dysphonic children and their parents. This study
      consisted of focused interviews with chronically dysphonic children and their
      caregivers. Focused interviews were conducted with 10 children in each of the
      following age groups: Toddler (2-4 years old), Young Child (5-7 years old),
      School-Aged Child (8-12 years old), and Adolescent (13-18 years old). Interview
      questions were formulated to elicit attitudes in the following conceptual
      domains: emotional, social/functional, and physical. Interviews were transcribed
      and subjected to systematic qualitative analyses that identified common themes
      within each age group for each conceptual domain. For Toddlers, interviews relied
      heavily on parents and the biggest concerns were found in the physical and
      functional domains. Young Children expressed that their biggest issues related to
      voice were physical ("run out of air," "sometimes voice does not work"). Ninety
      percent of Young Children were repeatedly asked to use a quieter voice. Emotional
      factors and physical factors were prominent in the interviews of School-Aged
      Children and Adolescents. Children and Adolescents often felt that their
      dysphonic voice received undue attention and also limited their participation in
      important events. Anger, sadness, and frustration were also expressed. Chronic
      dysphonia negatively affects the lives of children. This work will serve as the
      basis for development of a valid, reliable, and age-appropriate measure of voice
      related quality of life in children.

PMID- 17512169
TI  - Voice change in seasonal allergic rhinitis.
AB  - Voice problems are seldom reported in pollen allergy, although the allergic
      reaction involves the entire airways. The objective of this study was to
      investigate voice dysfunction during the pollen season in patients with allergic
      rhinitis. Thirty patients with verified birch pollen allergy and 30 controls were
      investigated twice, during the pollen season and outside the pollen season. Both
      times they scored respiratory and voice symptoms, the latter with the validated
      questionnaire Voice Handicap Index (VHI), and performed standardized voice
      recordings. These recordings were analyzed in a controlled manner by a
      professional voice therapist. During the allergy season, patients reported more
      respiratory and voice symptoms compared with controls. Those with blinded scored
      voice dysfunction scored their voice quality during springtime as 31 mm (95%
      confidence interval [CI] 20-42 mm), compared with 13 mm (95% CI 6-21 mm for
      participants without voice dysfunction (P<0.01). Furthermore, the group with
      experienced voice dysfunction scored significantly higher on the VHI in the
      functional and physical domains and in the total VHI score. Although voice
      problems during the pollen season are rarely discussed, in allergic rhinitis the
      larynx may also be involved. These findings support that some patients experience
      voice change, an experience which can be objectively confirmed.

PMID- 17512170
TI  - Acoustic changes in student actors' voices after 12 months of training.
AB  - This study was to evaluate acoustic changes in student actors' voices after 12
      months of actor training. The design used was a longitudinal study. Eighteen
      students enrolled in an Australian tertiary 3-year acting program (nine male and
      nine female) were assessed at the beginning of their acting course and again 12
      months later using a questionnaire, interview, maximum phonation time (MPT),
      reading, spontaneous speaking, sustained phonation tasks, and a pitch range task.
      Samples were analyzed for MPT, fundamental frequency across tasks, pitch range
      for speaking and reading, singing pitch range, noise-to-harmonic ratio, shimmer,
      and jitter. After training, measures of shimmer significantly increased for both
      male and female participants. Female participants' pitch range significantly
      increased after training, with a significantly lower mean frequency for their
      lowest pitch. The finding of limited or negative changes for some measures
      indicate that further investigation is required into the long-term effects of
      actor voice training and which parameters of voicing are most targeted and valued
      in training. Particular investigation into the relationship between training
      targets and outcomes could more reliably inform acting programs about changes in
      teaching methodologies. Further research into the relationship between specific
      training techniques, physiological changes, and vocal changes may also provide
      information on implementing more evidence-based training methods.

PMID- 17512171
TI  - Odor provocation test for laryngeal hypersensitivity.
AB  - This study was to present an odor provocation/challenge test for laryngeal
      hypersensitivity in a suspected odor induced dysphonic patient. The second aim
      was to rule out secondary gain from organic laryngeal hypersensitivity. Two steps
      were taken for this purpose. First, because the evaluation of hypersensitivity
      may be affected by the perception of odor, the study investigated laryngeal
      hypersensitivity during nasal and oral breathing separately to disentangle
      possible cognitive reactions to odors. Second, a healthy control (HC) participant
      was used with the identical testing protocol for nasal breathing to minimize
      unbiased results. The HC's response to nasal breathing of the odors showed no
      response to all the stimuli. The participant with possible secondary gain issues
      responded differently to the odors when presented nasally versus orally. Oral
      breathing showed less severe and less frequent laryngeal hypersensitive
      reactions. This suggests that laryngeal hypersensitivity was either due to the
      odor, cognitive information, sensory changes in olfaction leading to
      psychological conditioning, or for any possible secondary gain. Hence, it is
      difficult to indicate the precise reason (cause and effect) for the participant's
      laryngeal hypersensitivity; however, this study describes the first structured,
      controlled, repeatable, and randomized design to investigate odor induced
      laryngeal hypersensitivity and decipher possible secondary gain from true
      laryngeal hypersensitivity.

PMID- 17512172
TI  - Predictors of on-site vocational support for people with schizophrenia in
      supported employment.
AB  - This study examined predictors of intensity of vocational specialist support for
      clients with schizophrenia or schizoaffective disorder in supported employment.
      Sixty-nine outpatients with schizophrenia or schizoaffective disorder were
      recruited from a community mental health center for 12 months of vocational and
      cognitive rehabilitation. Neuropsychological test scores, symptom ratings,
      illness severity, and employment history were used to predict vocational support
      intensity, expressed as hours coached in ratio to total hours worked over 12
      months for each client. Weekly work hours were inversely correlated with
      intensity of vocational support. Half of the sample averaged 10 to 40 h of work
      per week and received significantly lower proportions of on-site job coaching
      than the lowest quartile, which averaged 2 to 5 h of work per week. Regressions
      predicting support intensity from neuropsychological composite scores,
      educational/vocational, and hospitalization history were not significant.
      Significant regressions included PANSS, SANS, and SAPS subscales, after which
      individual symptoms responsible for explained variance were isolated. SANS social
      inattention and PANSS active avoidance together predicted 23% of the variance in
      support intensity. A one-way ANOVA comparing work participation quartiles on
      these symptoms revealed significantly higher levels of active avoidance and
      social inattention for participants working less than 10 h per week. A profile
      emerged of the high intensity client as a socially inattentive or avoidant
      individual requiring a limited work schedule. Results suggest that these clients
      require more specialist contact because of failure to adequately engage natural
      supports at work.

PMID- 17512173
TI  - Neurological soft signs and minor physical anomalies in patients with
      schizophrenia and related disorders, their first-degree biological relatives, and
      non-psychiatric controls.
AB  - BACKGROUND: Subtle neurological impairments and inconsequential minor anomalies
      of the face and limbs are manifestations of neurodevelopmental and ontogenic
      abnormalities that are consistently found at higher rates in individuals with
      schizophrenia compared to healthy controls. Limited research has been conducted
      on these traits among biological relatives of patients with schizophrenia. This
      study hypothesized that the mean NSS score and the mean MPA score would be
      greater in patients than controls and that first-degree relatives would have
      intermediate scores. Furthermore, it was hypothesized that NSS scores and MPA
      scores would not be correlated. This study also explored correlations between
      patients' NSS and MPA scores and their relatives' respective scores and sought to
      replicate the finding that NSS are associated with negative and disorganized
      symptoms of schizophrenia, whereas MPAs are not. METHODS: Patients with
      schizophrenia and related psychotic disorders (n=73), first-degree relatives
      (n=44), and non-psychiatric controls (n=54) were assessed. Measures included the
      Neurological Evaluation Scale, a structured examination for MPAs, and the
      Positive and Negative Syndrome Scale in patients. Analyses accounted for
      clustering within families. RESULTS: Both NSS and MPAs were greater in patients
      than controls, and first-degree relatives had intermediate scores. Furthermore,
      NSS and MPA scores were independent in all three groups. Correlations were found
      between patients' and their relatives' scores on one NES subscale (sensory
      integration) and total MPA score and several MPA regions (eyes, ears, and hands).
      This study replicated previous findings that in patients with schizophrenia, NSS
      are associated with negative, disorganized, and other domains of symptoms.
      Associations between MPAs and symptoms were sparse and inconsistent. CONCLUSION:
      These findings suggest that NSS and MPAs represent two quite distinct markers of
      risk for schizophrenia that may stem from genetic factors, as well as from
      environmental/developmental influences. Future research on multivariable risk
      prediction models may benefit from the use of somewhat independent risk markers
      or endophenotypes.

PMID- 17512174
TI  - Stimulation of Langerhans cells with ketoprofen plus UVA in murine photocontact
      dermatitis to ketoprofen.
AB  - BACKGROUND: Ketoprofen (KP) clinically evokes the allergic type of photocontact
      dermatitis when applied to the skin and irradiated with ultraviolet A (UVA). We
      have established a murine model of photocontact dermatitis to KP, which is a T
      cell-mediated delayed type hypersensitivity. OBJECTIVE: To further explore the
      mechanism underlying this sensitivity, we investigated whether KP plus UVA
      activates the antigen-presenting ability of Langerhans cells (LCs). METHODS: We
      analyzed the expression of surface molecules on LCs in the murine epidermis
      treated with KP plus UVA by immunohistochemistry and flow cytometry. Changes in
      the cytokine expression of epidermal cells from KP-phototreated skin were also
      examined by real-time PCR. RESULTS: LCs became larger after treatment with KP
      plus UVA. The number of LCs was significantly decreased 2-3 days after KP
      phototreatment and recovered on day 5. A flow cytometric analysis revealed that
      KP plus UVA increased the percentage of LCs that highly expressed MHC class II,
      CD86, CD80, CD54 and CD40, whereas neither KP nor UVA alone enhanced the
      expression. KP phototreatment augmented the expression of I-A and CD86 on LCs in
      KP and UVA dose-dependent manners. A real-time PCR analysis of KP-phototreated
      skin showed that the expression of mRNA for IL-1alpha and GM-CSF was immediately
      increased after treatment. CONCLUSION: A photosensitizing regimen of KP plus UVA
      activates LCs at least partly by stimulating keratinocytes to produce cytokines.
      Two strains of mice (BALB/c and AKR) differ in responsiveness to KP and the
      difference is not related to the activation of keratinocytes.

PMID- 17512176
TI  - Theoretical assessment of a new experimental protocol for determining kinetic
      values describing mechanism (time)-based enzyme inhibition.
AB  - We have shown previously that the conventional experimental protocol (CEP) used
      to characterise mechanism-based enzyme inhibition (MBI) of drug metabolism in
      vitro may introduce substantial bias in estimates of the relevant kinetic
      parameters. The aim of this study was to develop and assess, by computer
      simulation, an alternative, mechanistically-based experimental protocol (MEP).
      This protocol comprises three parts viz. assessment of the metabolism of the
      mechanism-based enzyme inactivator (MBEI), of its ability to participate in
      competitive inhibition and its ability to cause time-dependent inhibition. Thus,
      values of the maximum inactivation rate constant (k(inact)), the inactivator
      concentration associated with half-maximal rate of inactivation (K(I)), the
      partition ration (r), and the reversible inhibition constant (K(i)) of the MBEI
      are determined by nonlinear optimization of the experimental data using a model
      that allows for metabolism of both probe substrate and MBEI, the time-course of
      inactivation of the enzyme, and reversible inhibition of the metabolism of both
      probe substrate and MBEI. Sensitivity analysis is used to estimate the degree of
      confidence in the final parameter values. Virtual experiments using the MEP and
      the CEP were simulated, applying starting kinetic parameters reported for 16
      known MBEIs. In the presence of simulated experimental error (5% CV), the MEP
      recovered accurate estimates of the kinetic values for all compounds, while
      estimates using the CEP were less accurate and less precise. The MEP promises to
      improve consistency in the determination of in vitro measures of MBI and,
      thereby, the quantitative assessment of its in vivo consequences.

PMID- 17512177
TI  - [Seasonal outbreak of enteroviral meningitis during summer 2005: experience of a
      French pediatric unit].
AB  - OBJECTIVE: To describe the clinical and biological characteristics of children
      presenting with enteroviral (EV) meningitis in a French paediatric unit during
      summer 2005. METHODS: Retrospective study of children with EV meningitis from May
      to September 2005, diagnosed by PCR and/or viral culture in cerebrospinal fluid
      (CSF), serum or throat. RESULTS: We reported 99 cases of EV meningitis (96
      confirmed and 3 probable). The sex ratio was 2/1, and the median age was 5 years.
      Peak incidence was reached during the second week of July. The predominant
      symptom was meningism. ENT (16%), digestive (10%), cutaneous (15%) or respiratory
      (4%) symptoms were rare. Blood leucocyte count found a predominance of
      neutrophils (73%), and lymphopenia in half of the children. The mean value of CRP
      was 25,5 mg/l. The median leukocyte count in CSF was 65 cells/mm(3), with a
      prevalence of neutrophils in 60% of cases. Pleiocytosis was absent in 20
      children. CSF protein level was increased in 20% of cases. The rate of
      hospitalization was 57,5%. Intravenous antibiotic treatment, initiated among 18
      patients, was stopped in 66,6% of the cases on reception of PCR result. The
      latter result was obtained in 2,3 days on average. CONCLUSION: The epidemic of
      2005 EV meningitis was as widespread as that of summer 2000. Characteristics of
      these meningitis are strong proportion of CSF without pleiocytose and high
      prevalence of neutrophils in blood and CSF.

PMID- 17512179
TI  - Phylogenetic relationships of Nemania plumbea sp. nov. and related taxa based on
      ribosomal ITS and RPB2 sequences.
AB  - During a survey fungal diversity of xylariaceous fungi in Thailand, a new Nemania
      species, N. plumbea, was identified. Nemania plumbea is characterized by soft
      textured grey stromata on a persistent mat of white hyphae, pale brown ascospores
      with a short germ-slit on the more convex side. It also produces a
      Geniculosporium-like anamorph in culture. In order to evaluate its phylogenetic
      relationships among related species and genera, ITS-5.8S rDNA and RPB2 were
      analysed separately and simultaneously. Results from the phylogenetic analyses
      indicate that there is close phylogenetic association between N. plumbea and N.
      aenea. A preliminary account into the natural grouping of Xylariaceae based on
      ITS-5.8S rDNA and RPB2 sequences is also discussed.

PMID- 17512178
TI  - [Performance of the Breastfeeding Assessment Score for the prediction of early
      weaning in France].
AB  - BACKGROUND: The Breastfeeding Assessment Score (BAS) was derived to help identify
      mothers at increased risk of early weaning in United States. Data are currently
      lacking on the accuracy of the BAS for French mother-infant pairs. OBJECTIVE: To
      assess the accuracy of the BAS in a French validation cohort. METHODS: We used
      the original data from a prospective cohort study of 488 mothers who were
      breastfeeding at discharge in 9 maternity wards in 2005. The outcome measures
      were assessed using structured follow-up telephone interviews at 4 and 26 weeks.
      RESULTS: The weaning rate was 3% at 14 days of infant age. The corresponding area
      under ROC curve was 0.73 [0.60-0.85] and was comparable to that observed in the
      derivation cohort (0.75). For a cut point of 8 recommended by the authors of the
      BAS, 43% of mother-infant pairs were categorized at high risk and the weaning
      rate in this subgroup was 5%. The mother-infant pairs with a score lower than 8
      had a shorter median breastfeeding duration (18 versus 20 weeks, P=0.02), were
      more likely to report breastfeeding difficulties after discharge (63% versus 53%,
      P=0.03), and were less likely to be "very satisfied" with breastfeeding
      experience (66% versus 77%, P=0.007). CONCLUSION: The intrinsic properties of the
      BAS are robust. However, its use would be of limited interest in France because
      of the relatively low rate of early weaning. Randomized trials are needed before
      recommending routine use of BAS-based breastfeeding support intervention.

PMID- 17512180
TI  - Anatomy and cytology of Taphrina entomospora during infection of Nothofagus.
AB  - Taphrina entomospora is one of the few species of the genus described on native
      plants of the Southern Hemisphere and also one of the few leaf pathogens known on
      Nothofagus species. The anatomical changes it produces on N. pumilio leaves, and
      its morphology, cytology, and sporogenesis were studied. The fungus is a
      perennial species that overwinters as mycelium in the foliar buds and infects the
      developing leaves, so the whole blade develops the disease symptoms. Interveinal
      areas of the leaves become chlorotic, thickened and rounded. Palisade parenchyma
      fails to develop, with spongy parenchyma developing as packed, rounded,
      isodiametric cells with little intercellular space. The mycelium is subcuticular,
      dikaryotic, and produces ascogenous hyphae, asci, and ascospores as described for
      other species in the genus. Before ascus discharge, ascospores bud in a regular,
      unique way. The life-cycle of T. entomospora is compared with other
      representative taxa in the genus and the distribution of this pathogen is
      discussed.

PMID- 17512181
TI  - Xerocomus silwoodensis sp. nov., a new species within the European X.
      subtomentosus complex.
AB  - A recent analysis of the Xerocomus subtomentosus complex in Europe using rDNA-ITS
      sequence data distinguished four taxa in Europe. Two of these corresponded to the
      established taxa X. subtomentosus and X. ferrugineus, and a new taxon, X.
      chrysonemus, was described. The fourth taxon was noted but left undescribed owing
      to lack of material. Here, we describe this taxon as X. silwoodensis sp. nov. X.
      silwoodensis is a rare but widespread taxon known from single sites in Italy and
      Spain, and three in the UK. The features of X. silwoodensis basidiomes are very
      similar to other members of the complex but the pileus colours tend to show
      richer red-brown tones and the stipe often radicates deeply into the substrate.
      The taxon also exhibits a strong preference for associating with Populus species,
      whereas the other taxa are associated with either Quercus (X. chrysonemus) or
      generalists on broadleaved hosts (X. subtomentosus) or conifers and broadleaved
      trees (X. ferrugineus). Microscopically, the spore characteristics of X.
      silwoodensis are similar to the recently described X. chrysonemus, but differ
      significantly from both X. subtomentosus and X. ferrugineus. X. silwoodensis is
      probably overlooked due to the resemblance to other taxa within the complex. The
      present study on the identification and description of X. silwoodensis should
      reduce the confusion associated with the identification of taxa within this
      species complex and lead to a more accurate assessment of the geographic
      distribution and conservation needs of the taxa.

PMID- 17512182
TI  - Mating systems in representatives of Parmeliaceae, Ramalinaceae and Physciaceae
      (Lecanoromycetes, lichen-forming ascomycetes).
AB  - The progeny of meiosis of eight Parmeliaceae, two Ramalinaceae and seven
      Physciaceae were subjected to fingerprint analysis using RAPD-PCR applied to
      single spore isolates. The sample set included common and widespread rarely
      fertile species (Parmelia sulcata, Pseudevernia furfuracea, Physcia tenella),
      local to common, infrequently fertile species (Melanelixia glabra, Parmelina
      tiliacea, Xanthoparmelia conspersa, X. stenophylla, Anaptychia runcinata,
      Diploicia canescen, Physconia distorta), local to rare, infrequently or regularly
      fertile species with declining distributions (Parmelina carporrhizans, P.
      quercina, Ramalina fastigiata, R. fraxinea, Anaptychia ciliaris), and local to
      common, regularly fertile species (Physcia aipolia, P. stellaris). All species
      turned out to be heterothallic, polymorphisms among RAPD markers ranging from 10
      87%. The significance of these findings for population genetics and conservation
      biology, and potential reasons for infrequent ascoma formation in some of the
      species are discussed.

PMID- 17512183
TI  - Effect of organic residues addition on the technological properties of clay
      bricks.
AB  - The objective of this study is to investigate the utilization potential of
      several organic residues in clay bricks. Sawdust, tobacco residues, and grass are
      widespread by-products of industrial and agricultural processes in Turkey. These
      residue materials have long cellulose fibres. Sawdust and tobacco residues
      generally are used as fuel, and the grass is utilized for agricultural purposes.
      The insulation capacity of brick increases with the increasing porosity of the
      clay body. Combustible, organic types of pore-forming additives are most
      frequently used for this purpose. For this reason, increasing amounts of organic
      residues (0%, 2.5%, 5% and 10% in wt.) were mixed with raw brick-clay. All
      samples were fired at 900 degrees C. Effects on shaping, plasticity, density, and
      mechanical properties were investigated. The organic residue additions were found
      to be effective for pore-forming in the clay body with the clay maintaining
      acceptable mechanical properties. It was observed that the fibrous nature of the
      residues did not create extrusion problems. However, higher residue addition
      required a higher water content to ensure the right plasticity. As a result,
      sawdust, tobacco residues, and grass can be utilized in an environmentally safe
      way as organic pore-forming agents in brick-clay.

PMID- 17512184
TI  - Generation, storage, collection and transportation of municipal solid waste--a
      case study in the city of Kathmandu, capital of Nepal.
AB  - Solid waste management (SWM) services have consistently failed to keep up with
      the vast amount of solid waste produced in urban areas. There is not currently an
      efficient system in place for the management, storage, collection, and
      transportation of solid waste. Kathmandu City, an important urban center of South
      Asia, is no exception. In Kathmandu Metropolitan City, solid waste generation is
      predicted to be 1091 m(3)/d (245 tons/day) and 1155 m(3)/d (260 tons/day) for the
      years 2005 and 2006, respectively. The majority (89%) of households in Kathmandu
      Metropolitan City are willing to segregate the organic and non-organic portions
      of their waste. Overall collection efficiency was 94% in 2003. An increase in
      waste collection occurred due to private sector involvement, the shutdown of the
      second transfer station near the airport due to local protest, a lack of funding
      to maintain trucks/equipment, a huge increase in plastic waste, and the
      willingness of people to separate their waste into separate bins. Despite a
      substantial increase in total expenditure, no additional investments were made to
      the existing development plan to introduce a modern disposal system due to
      insufficient funding. Due to the lack of a proper lining, raw solid waste from
      the existing dumping site comes in contact with river water directly, causing
      severe river contamination and deteriorating the quality of the water.

PMID- 17512185
TI  - Reagentless aptamer based impedance biosensor for monitoring a neuro-inflammatory
      cytokine PDGF.
AB  - Neural prostheses often suffer from undesired chronic inflammatory tissue
      response. This can lead to neuronal loss and formation of glial scar tissue,
      which would serve as a barrier to neural signal transduction. In situ monitoring
      of neuro-inflammatory cytokines may improve our understanding of device induced
      inflammatory responses. Furthermore, early detection of the onset and degree of
      inflammation and releasing drugs accordingly may lead to improved long term
      performance of such implanted devices. For this reason, biosensor applying
      aptamer as probe and non-faradic electrochemical impedance spectroscopy (NIS) as
      the detection method has been developed. Aptamers, certain kinds of DNA or RNA
      molecules which can bind variety of molecules at high specificity, have the
      overwhelming advantages over antibodies of low cost and ease of use. Platelet
      derived growth factor BB (PDGF-BB), one of the important cytokines involved in
      neural inflammation, has been selected as our detection target. Binding of PDGF
      to its aptamer immobilized on the silicon electrode surface lead to a decrease in
      capacitance measured by NIS. A good linear relationship between the decrease of
      capacitance and the logarithm of protein concentration was obtained, which proves
      the feasibility of quantitative measurements. By sweeping the applied electrode
      potential of potentiostatic EIS, -0.1 V to +0.1 V was determined to be the
      optimal range for achieving best discrimination between specific target binding
      and non-specific protein adsorption on aptamer-modified silicon surface. Under
      such conditions, the specificity of the detection measured by the ratio of the
      positive to negative control is around 10:1 and the detection limit is
      approximately 1 microg/ml (40 nM). The online measurement result exhibited
      negligible response for non-specific adsorption but significant signal changes
      for the specific target. Since the non-faradic strategy does not require any
      reagent to be loaded when performing the test, together with the ability of
      online measurements, this biosensor design is promising for in vivo monitoring.

PMID- 17512186
TI  - SPR biosensor for the detection of L. monocytogenes using phage-displayed
      antibody.
AB  - Whole cells of Listeria monocytogenes were detected with a compact, surface
      plasmon resonance (SPR) sensor using a phage-displayed scFv antibody to the
      virulence factor actin polymerization protein (ActA) for biorecognition. Phage Lm
      P4:A8, expressing the scFv antibody fused to the pIII surface protein was
      immobilized to the sensor surface through physical adsorption. A locally
      constructed fluidics system was used to deliver solutions to the compact, two
      channel SPREETA sensor. Specificity of the sensor was tested using common food
      borne bacteria and a control phage, M13K07 lacking the scFv fusion on its coat
      protein. The detection limit for L. monocytogenes whole cells was estimated to be
      2 x 10(6)cfu/ml. The sensor was also used to determine the dissociation constant
      (Kd) for the interaction of phage-displayed scFv and soluble ActA in solution as
      4.5 nM.

PMID- 17512187
TI  - Identification of high-stringency DNA hairpin probes by partial gene folding.
AB  - Hairpin DNA sequences are widely used as probes for oligonucleotides in a broad
      range of assays, often as "molecular beacons". A potential disadvantage of the
      standard methodology for molecular beacon design is the need to add several self
      complementary bases to each end of the probe, since these do not correspond to
      the target sequence. We describe a conceptually new method of hairpin DNA probe
      identification, in which a secondary structure prediction algorithm is employed
      to identify oligonucleotide sequences within an expressed gene having the
      requisite hairpin structure. Intuitively, such probes should have significantly
      improved performance over "traditional" hairpin probes, because they are fully
      complementary with the target. We present experimental evidence verifying this
      hypothesis for a series of hairpin probes targeting the pag gene of Bacillus
      anthracis.

PMID- 17512188
TI  - Stable enzyme biosensors based on chemically synthesized Au-polypyrrole
      nanocomposites.
AB  - This work describes development and optimization of a generic method for the
      immobilization of enzymes in chemically synthesized gold polypyrrole (Au-PPy)
      nanocomposite and their application in amperometric biosensors. Three enzyme
      systems have been used as model examples: cytochrome c, glucose oxidase and
      polyphenol oxidase. The synthesis and deposition of the nanocomposite was first
      optimized onto a glassy carbon electrode (GCE) and then, the optimum procedure
      was used for enzyme immobilization and subsequent fabrication of glucose and
      phenol biosensors. The resulting nanostructured polymer strongly adheres to the
      surface of the GCE electrode, has uniform distribution and is very stable. The
      method has proved to be an effective way for stable enzyme attachment while the
      presence of gold nanoparticles provides enhanced electrochemical activity; it
      needs very small amounts of pyrrole and enzyme and the Au-PPy matrix avoids
      enzyme leaking. The preparation conditions, Michaelis-Menten kinetics and
      analytical performance characteristics of the two biosensors are discussed.
      Optimization of the experimental parameters was performed with regard to pyrrole
      concentration, enzyme amount, pH and operating potential. These biosensors
      resulted in rapid, simple, and accurate measurement of glucose and phenol with
      high sensitivities (1.089 mA/M glucose and 497.1 mA/M phenol), low detection
      limits (2 x 10(-6)M glucose and 3 x 10(-8)M phenol) and fast response times (less
      than 10s). The biosensors showed an excellent operational stability (at least 100
      assays) and reproducibility (R.S.D. of 1.36%).

PMID- 17512189
TI  - Oesophageal cancer in The Netherlands: increasing incidence and mortality but
      improving survival.
AB  - AIM: Oesophageal cancer is highly lethal with a 5-year relative survival of 10
      15%. An increasing incidence has been reported for several parts of the Western
      world. We studied time trends in incidence, mortality and survival for
      oesophageal cancer in the Netherlands during 1989-2003. METHODS: Data on
      incidence and survival were obtained from the Netherlands Cancer Registry and
      mortality data from Statistics Netherlands. RESULTS: The age standardised
      incidence increased by 3.4% (p<0.001) and 1.9% (p=0.003) per year for males and
      females, respectively. This increase was almost exclusively caused by oesophageal
      adenocarcinomas. Age standardised mortality increased 2.5% (p<0.001) per year
      among males and 1.7% (p=0.002) per year among females. Relative survival improved
      significantly from 8.1% in 1989-1993 to 12.6% in 1999-2003 (p<0.001). Adjusted
      for age, stage, tumour location and surgery, the excess risk of death decreased
      by 22%. CONCLUSION: Oesophageal carcinoma incidence is rising in the Netherlands.
      Mortality increased at a slightly lower pace due to improving survival.

PMID- 17512190
TI  - The maximum uptake of (18)F-deoxyglucose on positron emission tomography scan
      correlates with survival, hypoxia inducible factor-1alpha and GLUT-1 in non-small
      cell lung cancer.
AB  - The purpose of this study was to investigate the relation between the
      standardised uptake value (SUV) on (18)F-fluoro-2-deoxy-glucose-positron emission
      tomography scan and hypoxia related markers (HIF-1alpha and CAIX), a
      proliferation-related marker (Ki-67) and glucose transporters (GLUT-1 and GLUT-3)
      in non-small cell lung cancer (NSCLC). One hundred and two patients, scheduled
      for complete resection, received a PET scan in Leuven or Maastricht/Aachen. The
      maximal SUV (SUV(max)) was correlated with survival and immunohistochemical
      staining patterns. The actuarial survival was worse for patients showing a high
      SUV(max), the best discriminative value being 8.0 (Leuven, p=0.032) and 11.0
      (Maastricht, p=0.007). Tumours with a high SUV(max) expressed in a higher
      proportion HIF-1alpha (63.1% versus 37.9%, p=0.024) and GLUT-1 (82.9% versus
      62.5%, p=0.025), than tumours with a low SUV(max). No significant difference was
      found in the expression of CAIX, Ki-67 and GLUT-3. This study supports
      preclinical data that hypoxia is associated with a higher uptake of FDG.

PMID- 17512191
TI  - Circulating adiponectin levels in relation to melanoma: a case-control study.
AB  - AIM: Melanoma, a malignancy with steadily increasing prevalence, has been
      associated not only with sun exposure but also with phenotypic characteristics
      including obesity. Adiponectin, an adipocyte secreted endogenous insulin
      sensitizer, has been found to play a protective role in several obesity related
      cancers but has not yet been studied in relation to melanoma. We investigated the
      association of circulating adiponectin levels with melanoma in Greece, a country
      with rather low incidence of the disease and high annual sunshine levels.
      METHODS: In the context of a case-control study, we studied over a 22-month
      period 55 patients with incident, histologically confirmed melanoma cases and 165
      healthy controls matched for gender and age. RESULTS: After controlling for the
      possible confounding effect of education, body mass index and waist-to-hip ratio
      in multiple logistic regression analyses, sun sensitive skin type was
      significantly and positively associated with melanoma risk (OR: 2.48, 95%
      Confidence Interval: 1.22-5.10, p: 0.01). On the contrary, there was a sizeable,
      though non-significant, inverse association of serum adiponectin levels with the
      disease (OR: 0.75, 95% Confidence Interval: 0.52-1.10, p: 0.14). CONCLUSION: A
      protective role of adiponectin in the development of melanoma cannot be excluded
      given the presented empirical evidence (25% reduction per one SD of adiponectin)
      and the direct anti-neoplastic features of the hormone. The results are
      intriguing enough to point to the need for further investigation.

PMID- 17512192
TI  - Value of complete metabolic response by (18)F-fluorodeoxyglucose-positron
      emission tomography in oesophageal cancer for prediction of pathologic response
      and survival after preoperative chemoradiotherapy.
AB  - We aimed to assess the ability of (18)F-fluorodeoxyglucose (FDG)-positron
      emission tomography (PET) scan to predict pathologic complete response (CR) and
      survival in patients with oesophageal cancer treated with preoperative
      chemoradiotherapy (CRT). The study cohort consisted of 62 consecutive patients
      with operable oesophageal cancer who were treated with preoperative CRT followed
      by oesophagectomy. Endoscopy, computed tomography (CT) and PET were performed
      before and after CRT. Of the 62 patients, 56 (90%) patients responded to
      preoperative CRT. FDG-PET-determined complete metabolic response (CMR) was
      achieved by 33 patients (54.1%), whereas pathologic CR was achieved by 28
      patients (45.2%). Compared with endoscopic biopsy or CT scan, CMR by FDG-PET
      showed the highest correlation with pathologic CR (concordance, 71%). At a median
      follow-up of 19.3 months (range, 3.9-57.1 months), median overall survival (OS)
      was not reached in patients with CMR compared to 22.4 months in patients who did
      not achieve CMR. Median disease free survival (DFS) was not reached in patients
      with CMR compared to 17.4 months in patients who did not achieve CMR. By
      multivariate analysis, CMR by FDG-PET was significantly associated with better
      DFS and OS (P=0.006, P=0.033, respectively). The variables associated with pre
      CRT PET scan were not predictive of survival. In conclusion, CMR by FDG-PET has a
      significant correlation with pathologic CR and can predict the long-term outcome
      in oesophageal cancer patients undergoing CRT. Although surgery is standard
      treatment for respectable oesophageal cancer, currently even in patients with
      CMR, the addition of (18)F-FDG-PET could be used to select the patient subgroup
      not requiring surgery.

PMID- 17512193
TI  - Neurosteroids alter glutamate-induced changes in neurite morphology of NG108-15
      cells.
AB  - Activation of the NMDA receptor leads to increased intracellular Ca2+ levels
      ([Ca2+]i) which induces outgrowth of and morphologic changes in the neurites of
      the NG108-15 cell line. This effect can be blocked by antagonists for this
      glutamate receptor subtype (e.g. ifenprodil or AP5). We have previously shown
      that nanomolar concentrations of various neurosteroids modulate ifenprodil
      binding to the NMDA receptor. To investigate whether this interaction affects the
      functioning of the receptor, we studied the effect of 24 and 48 h of pregnenolone
      sulphate (PS) or pregnanolone sulphate (3alpha5betaS) on glutamate-stimulated
      NG108-15 cells. Unexpectedly, the neurosteroids themselves had an inhibitory
      effect on glutamate-induced changes in neurite patterns. This effect was
      comparable to that of ifenprodil or AP5. Moreover, the effect of combined
      treatment with 3alpha5betaS and ifenprodil on neurite morphology indicated a
      functional interaction between the substances. Interestingly, PS induced cell
      detachment over time, an effect that was further enhanced by ifenprodil. Cell
      detachment was also seen after 48 h of treatment with 3alpha5betaS; however, the
      effect was blocked by ifenprodil and weaker than that of PS. The interaction with
      the NR2B-selective antagonist ifenprodil indicates that this NMDA receptor
      subunit may be involved in neurosteroid-induced NG108-15 cell detachment.

PMID- 17512194
TI  - Odour sampling. 2. Comparison of physical and aerodynamic characteristics of
      sampling devices: a review.
AB  - Sampling devices differing greatly in shape, size and operating condition have
      been used to collect air samples to determine rates of emission of volatile
      substances, including odour. However, physical chemistry principles, in
      particular the partitioning of volatile substances between two phases as
      explained by Henrys Law and the relationship between wind velocity and emission
      rate, suggests that different devices cannot be expected to provide equivalent
      emission rate estimates. Thus several problems are associated with the use of
      static and dynamic emission chambers, but the more turbulent devices such as wind
      tunnels do not appear to be subject to these problems. In general, the ability to
      relate emission rate estimates obtained from wind tunnel measurements to those
      derived from device-independent techniques supports the use of wind tunnels to
      determine emission rates that can be used as input data for dispersion models.

PMID- 17512195
TI  - Composting and vermicomposting experiences in the treatment and bioconversion of
      asphaltens from the Prestige oil spill.
AB  - This work illustrates the effectiveness of composting and vermicomposting in
      degrading fuel-in-water emulsions from oil spills (chapapote), and the isolation
      of potentially useful microorganisms for its biodegradation. Firstly, an
      alternative to the biodegradation of asphaltens from the Prestige oil spill
      (still present in some chapapote rafts in the Cantabrian coast) by means of the
      application of composting techniques to a microbial partnership acclimated to
      fuel-oil is offered. Our aim is that, after a relatively short period of time,
      the microorganisms can obtain its source of carbon and energy from asphaltens.
      The addition of metabolic co-substrates, like cow bed and potato peelings, allows
      the fragmentation of complex compounds into smaller structures, susceptible to
      further degradation. Afterwards, a maturation of the compost by means of a
      treatment with earthworms (Eisenia foetida) is necessary. Thus, through the
      vermicomposting it will be possible to obtain a valued product, useful in the
      processes of ground amendment, with little presence of asphaltens and occluded
      polycyclic aromatic hydrocarbons, rich in humus, and with an important bacterial
      flora of Bacillus genera, so that it can be typical of co-activators and
      accelerating products in composting processes. Along with this article, we show
      some parameters that control the evolution of the compost products (evolved
      gases, acidity, temperature and humidity); the chemical and microbiological
      analytical results; and the germination assays of vermicomposting. Results reveal
      that by using microorganisms living in either earthworm intestines
      (Stenotrophomonas maltophilia) or vermiculture substrates (Scedosporium
      apiospermium), it is possible to degrade and to eliminate the polycyclic
      asphaltens into CO(2) and H(2)O, helped by evaporation, dissolution and/or photo
      oxidation processes. The obtained end product has contents of interesting vegetal
      nutrients and, mainly, it displays very high germination indices.

PMID- 17512196
TI  - Evaluation of in vitro aldose redutase inhibitory activity of 5-arylidene-2,4
      thiazolidinediones.
AB  - A number of 5-arylidene-2,4-thiazolidinediones containing a hydroxy or a
      carboxymethoxy group in their 5-benzylidene moiety have been synthesised and
      evaluated as in vitro aldose reductase (ALR2) inhibitors. Most of them exhibited
      strong inhibitory activity, with IC(50) values in the range between 0.20 and 0.70
      microM. Molecular docking simulations into the ALR2 active site highlighted that
      the phenolic or carboxylic substituents of the 5-benzylidene moiety can
      favourably interact, in alternative poses, either with amino acid residues lining
      the lipophilic pocket of the enzyme, such as Leu300, or with the positively
      charged recognition region of the ALR2 active site.

PMID- 17512197
TI  - Synthesis and SAR of selective benzothiophene, benzofuran, and indole-based
      peroxisome proliferator-activated receptor delta agonists.
AB  - Recent literature has suggested the benefit of selective PPARdelta agonists for
      the treatment of atherosclerosis and other disease states associated with the
      metabolic syndrome. Herein we report the synthesis and structure-activity
      relationships of a series of novel and selective PPARdelta agonists. Our search
      began with identification of a novel benzothiophene template which was modified
      by the addition of various thiazolyl, isoxazolyl, and benzyloxy-benzyl moieties.
      Further elucidation of the SAR led to the identification of benzofuran and indole
      based templates. During the course of our research, we discovered three new
      chemical templates with varying degrees of affinity and potency for PPARdelta
      versus the PPARalpha and PPARgamma subtypes.

PMID- 17512198
TI  - Discovery of novel dialkyl substituted thiophene inhibitors of HCV by in silico
      screening of the NS5B RdRp.
AB  - A novel 5,4-dialkyl substituted thiophene was discovered by in silico screening
      of the 3D polymerase crystal structure (1GX6) that demonstrated single digit
      micromolar HCV inhibition activity in the replicon assay and dose-dependent
      inhibition in the replicase complex assay. Subsequently, SAR was explored with a
      small set of dialkyl and tetrahydro-benzo thiophenes. Since these thiophenes
      inhibit synthesis of both, single- and double-stranded RNAs, their mechanism of
      action is distinct from other known HCV inhibitors.

PMID- 17512199
TI  - SAR of the arylpiperazine moiety of obeline somatostatin sst1 receptor
      antagonists.
AB  - The SAR of over 50 derivatives of octahydrobenzo[g]quinoline (obeline)-type
      somatostatin sst(1) receptor antagonist 1 is presented, focusing on the
      modification of its arylpiperazine moiety. Sst(1) affinities in this series cover
      a range of five orders of magnitude with the best derivatives displaying
      subnanomolar sst(1) affinities and >10,000-fold selectivities over the sst(2)
      receptor subtype as well as promising pharmacokinetic properties.

PMID- 17512200
TI  - Part 2. Chemical and physical restraints in the management of mechanically
      ventilated patients in the ICU: a patient perspective.
AB  - An important goal of the care for the mechanically ventilated patient is to
      minimize patient discomfort and anxiety. This is partly achieved by frequent use
      of chemical and physical restraints. The majority of patients in intensive care
      will receive some form of sedation. The goal and use of sedation has changed
      considerably over the past few decades with literature evidencing trends toward
      overall lighter sedation levels and daily interruption of sedation. Conversely,
      the use of physical restraint for the ventilated patient in ICU differs
      considerably between nations and continents. A large portion of the literature on
      the use of physical restraint is from general hospital wards and residential
      homes, and not from the ICU environment. Recent literature suggests minimal use
      of physical restraint in the ICU, and that reduction programmes have been
      initiated. However, very few papers illuminate the patient's experience of
      physical and chemical restraints as a treatment strategy. In Part 1 of this two
      part review, the evidence on chemical and physical restraints was explored with
      specific focus on definitions of terms, unplanned extubation, agitation, delirium
      as well as the impact of nurse-patient ratios in the ICU on these issues. This
      paper, Part 2, examines the evidence related to chemical and physical restraints
      from the mechanically ventilated patient's perspective.

PMID- 17512201
TI  - Characteristics of personal space during obstacle circumvention in physical and
      virtual environments.
AB  - It is not known how the flexible protective zone maintained around oneself during
      locomotion (personal space or PS; see [Gerin-Lajoie M, Richards CL, McFadyen BJ.
      The negotiation of stationary and moving obstructions during walking:
      anticipatory locomotor adaptations and preservation of personal space. Motor
      Control 2005;9:242-69]) is modulated with walking speed, whether both sides of
      the PS are symmetrical, and whether the circumvention of physical and virtual
      obstructions elicit the same use of such PS. Personal space was measured in ten
      adults as they circumvented a cylindrical obstacle that was stationary within
      their path. Both left and right passes were performed at natural self-selected,
      slow and fast walking speeds. The same circumvention task was also performed at
      natural speeds in an immersive virtual environment (VE) replicating the same
      obstruction scenario. The shape and size of PS were maintained across walking
      speeds, and a smaller PS was generally observed on the dominant side. The general
      shape and lateral bias of the PS were preserved in the VE while its size was
      slightly increased. The systematic behavior across walking speeds and types of
      environment and the lateral bias suggest that PS is used to control navigation.
      This study deepens our understanding of normal adaptive walking behavior and has
      implications for the development of better tools for the assessment and
      retraining of locomotor capacity in different populations, from people with
      walking deficits to elite athletes. Since the PS behavior was shown to be robust
      in the VE used for this study, the virtual reality technology is proposed as a
      promising platform for the development of such assessment and retraining
      applications.

PMID- 17512202
TI  - Fluorescence-based detection of short DNA sequences under non-denaturing
      conditions.
AB  - The ability of peptide nucleic acid (PNA) to open up duplex DNA in a highly
      sequence-specific manner makes it possible to detect short DNA sequences on the
      background of or within genomic DNA under non-denaturing conditions. To do so,
      chosen marker sites in double-stranded DNA are locally opened by a pair of PNA
      openers, thus transforming one strand within the target region (20-30 bp) into
      the single-stranded form. Onto this accessible DNA sequence a circular
      oligonucleotide probe is assembled, which serves as a template for rolling circle
      amplification (RCA). Both homogeneous and heterogeneous assay formats are
      investigated, as are different formats for fluorescence-based amplicon detection.
      Our recent data with immobilized analytes suggest that marker sequences in
      plasmid and bacterial chromosomal DNA can be successfully detected.

PMID- 17512203
TI  - Effects of oxygen-sulfur substitution on glycosaminoglycan-priming
      naphthoxylosides.
AB  - Three series of sulfur-containing analogs to the selectively antiproliferative 2
      (6-hydroxynaphthyl) beta-D-xylopyranoside were synthesized and their biological
      properties investigated. A short, general route to hydroxynaphthyl disulfides
      from dihydroxynaphthalenes was developed to utilize the disulfide bond as a
      sulfur-selective protecting group to enable the orthogonal protection of
      hydroxyls and thiols. The results indicate that hydrophobic, uncharged oxygen
      sulfur substituted naphthoxylosides are taken up by cells and initiate priming of
      GAG chains to a greater extent compared to the oxygen analogs. No correlation
      between priming ability and antiproliferative activity was observed.

PMID- 17512204
TI  - Synthesis and structure-activity relationships of new antiproliferative and
      proapoptotic retinoid-related biphenyl-4-yl-acrylic acids.
AB  - Atypical retinoids, or retinoid-related molecules (RRMs), represent a class of
      proapoptotic agents with a promising potential in the treatment of neoplastic
      diseases. In the present work, the synthesis and structure-activity relationship
      of a series of 3'-adamantan-1-yl-biphenyl-4-yl-acrylic acids substituted in ring
      A were studied. The synthesized compounds were evaluated for their
      antiproliferative activity in a human promyelocitic leukemia cell line (NB4), and
      in an ovarian carcinoma cell system including IGROV-1, carrying a functional wild
      type p53, and a cisplatin-resistant subline, IGROV-1/Pt-1. The presence of at
      least one oxygenated substituent in positions 4' or 5' appears determinant for
      the antiproliferative activity. With two substituents of this kind the activity
      increases, particularly in the case of alkylenedioxy compounds. The activation of
      DNA damage response as indicated by phosphorylation of H2AX histone, RPA-2
      protein, and p53 at serine 15 by the most apoptotic compounds provides additional
      support to the hypothesis that the genotoxic stress is a critical event mediating
      apoptosis induction by compounds of this group.

PMID- 17512205
TI  - Distribution of radiocesium and natural gamma emitters in pine needles in
      coniferious forest sites of Izmir.
AB  - Using a high-resolution gamma-spectrometer system, the activity concentrations of
      7Be, 137Cs, 40K and 226Ra were determined in the pine needles. Activity
      concentrations of the concerned radionuclides in the needle samples were as
      follows: 7Be, 24.6+/-2.40 to 210+/-7.21 Bq kg(-1), 40K, 23.5+/-12.4 to 287+/-15.6
      Bq kg(-1), 226Ra, 0.44+/-0.12 to 12.3+/-2.18 Bq kg(-1), and 137Cs, 0.61+/-0.30 to
      2.29+/-0.38 Bq kg(-1). It is found that the frequency distributions obtained for
      7Be and 137Cs can be fitted to a normal distribution, and for 40K and 226Ra can
      be fitted to a log-normal distribution.

PMID- 17512207
TI  - Energy dispersive X-ray diffraction as a means to identify illicit materials: a
      preliminary optimisation study.
AB  - Energy dispersive X-ray diffraction is proposed as a suitable non-destructive
      method to rapidly identify illicit drugs in parcels. A preliminary data set of 7
      illicit drug samples and a possible cutting agent has been collected with a range
      of count times using a tungsten target X-ray source, a high resolution HpGe
      detector and a variable geometry diffraction cell. These results have been used
      to calibrate and train multivariate analysis software to predict the drug content
      in previously unseen spectra.

PMID- 17512209
TI  - The papillary muscles as shock absorbers of the mitral valve complex. An
      experimental study.
AB  - OBJECTIVE: Although it is known that the papillary muscles ensure the continuity
      between the left ventricle (LV) and the mitral apparatus, their precise mechanism
      needs further study. We hypothesize that the papillary muscles function as shock
      absorbers to maintain a constant distance between their tips and the mitral
      annulus during the entire cardiac cycle. MATERIALS AND METHODS: Sonomicrometry
      crystals were implanted in five sheep in the mitral annulus at the trigones (T1
      and T2), mid anterior annulus (AA) mid posterior annulus (PA), base of the
      posterior lateral scallops (P1 and P2), tips of papillary muscles (M1 and M2),
      and LV apex. LV and aortic pressures were simultaneously recorded and used to
      define the different phases of the cardiac cycle. RESULTS: No significant
      distance changes were found during the cardiac cycle between each papillary
      muscle tip and their corresponding mitral hemi-annulus: M1-T1, (3.5+/-2%); M1-P1
      (5+/-2%); M1-PA (5+/-3%); M2-T2 (2.7+/-2%); M2-P2 (6.1+/-3%); and M2-AA (4.2+/
      3%); (p>0.05, ANOVA). Significant changes were observed in distances between each
      papillary muscle tip and the contralateral hemi-mitral annulus: M1-T2 (1.7+/-3%);
      M1-P2 (23+/-6%); M1-AA (6+/-3%); M2-T1 (8+/-3%); M2-P1 (10.5+/-6%); and M2-PA
      (12.6+/-8%); (p<0.05 ANOVA). The distance changes between LV apex and each
      papillary muscle tip were significantly different: apex-M1 (12.9+/-1%) and apex
      M2 (10.5+/-1%) and different from the averaged distance change between the LV
      apex and each annulus crystal (8.3+/-1%) with p<0.05. CONCLUSION: The papillary
      muscles seem to be independent mechanisms designed to work as shock absorbers to
      maintain the basic mitral valve geometry constant during the cardiac cycle.

PMID- 17512210
TI  - Clinical results of staged repair with complete unifocalization for pulmonary
      atresia with ventricular septal defect and major aortopulmonary collateral
      arteries.
AB  - OBJECTIVE: Our treatment strategy for pulmonary atresia with ventricular septal
      defect (VSD) and major aortopulmonary collateral arteries is a staged repair that
      comprises the first complete unifocalization (UF) with 'unification' of
      intrapulmonary arteries and then the definitive repair. The purpose of this study
      is to evaluate the outcome of our staged repair strategy with complete UF and to
      determine the results of our current management strategy. METHODS: From 1982 to
      2004, 113 consecutive patients were treated with staged repair at our institute.
      We evaluated the risk of definitive repair failure or death in the 3 years after
      definitive repair using logistic regression. Furthermore, we compared the early
      group (patients who underwent UF before December 1995) and the late group
      (patients who underwent UF after January 1996). RESULTS: The mean follow-up
      interval was 8.8 years (0.8 months to 23.3 years), and Kaplan-Meier-estimated
      overall survival rates after first UF were 80.9, 73.8, and 69.9% at 5, 10, and 15
      years, respectively. Survival in patients with an absent central pulmonary artery
      (PA) was significantly lower than in those with a central PA (p<0.05), and the
      factor that was significantly associated with definitive repair failure or death
      in the 3 years after definitive repair was central PA morphology (p<0.05). Higher
      mean PA pressure after UF was detected in patients with hypoplastic central PA,
      compared with those without hypoplastic PA (30.9 mmHg vs 23.3 mmHg, p<0.05). In
      the late group, age (in years) at first UF (3.9 vs 8.4, p<0.01), second UF (4.3
      vs 9.2, p<0.01), and definitive repair (5.8 vs 9.1, p<0.01) was significantly
      younger than in early group, and the survival rate after first UF in the late
      group was 96.2 and 91.3% at 3 and 7 years, respectively. Systolic right
      ventricular pressure and the pressure ratio between the right and the left
      ventricles after definitive repair in the late group were significantly lower
      than in the early group (53.6 mmHg vs 75.0 mmHg, p<0.01; 61.7% vs 75.9%, p<0.05).
      CONCLUSIONS: Hypoplastic central PA was a significant risk factor in this
      disease. The overall survival was improved by our current management strategy.
      Improved RV pressure after definitive repair appears to affect the long-term
      outcome.

PMID- 17512211
TI  - Toxoplasma gondii triggers secretion of interleukin-12 but low level of
      interleukin-10 from the THP-1 human monocytic cell line.
AB  - Previous studies using both in vitro and in vivo mouse models have demonstrated
      that a subtle balance between pro- and anti-inflammatory cytokines, among which
      interleukin-12 (IL-12) and interleukin-10 (IL-10), respectively is crucial to
      control Toxoplasma infection. However, the few studies performed with human cell
      lines highlighted important host-related differences in the immune response to
      Toxoplasma gondii. The goal of our work was thus to study the production of both
      IL-12 and IL-10 by the THP-1 human monocytic cell line in response to Toxoplasma.
      We demonstrated that infection by live parasites (RH strain) triggers secretion
      of IL-12, but low level of IL-10. IL-12 secretion appeared within 8 h, up to 48
      h. We also showed that infection by live parasites is not mandatory since heat
      killed parasites, crude tachyzoite lysate as well as excreted/secreted antigens
      induced significant, yet reduced production of IL-12.

PMID- 17512212
TI  - Effect of hepatocyte growth factor on long term hematopoiesis of human progenitor
      cells in transgenic-severe combined immunodeficiency mice.
AB  - Hepatocyte growth factor (HGF), which was originally isolated as a liver
      generating factor, enhances hematopoiesis. To study the effect of HGF on
      hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs), we
      generated severe combined immunodeficiency (SCID) mice producing human (h) HGF
      and/or stem cell factor (SCF) by transferring the relevant genes to fertilized
      eggs, and then transplanted hematopoietic progenitors from human cord blood into
      the transgenic (Tg) SCID mice. Six months after transplantation, a significantly
      larger number of human cells were found in the Tg SCID mice than in non-Tg
      controls. Characteristically, the recipient SCID mice producing h HGF (HGF-SCID)
      had a significantly increased number of h CD41+ cells, whereas the SCF-SCID
      recipients had more CD11b+ cells. Significantly large numbers of CD34+
      progenitors were found in the SCID mice transferred with both h HGF and h SCF
      genes (HGF/SCF-SCID) when compared with HGF-SCID or SCF-SCID mice. These results
      imply that HGF supports the differentiation of progenitors in megakaryocyte
      lineage, whereas SCF supports that in myeloid lineage. The results also imply
      that HGF acts on HSCs/HPCs as a synergistic proliferative factor combined with
      SCF. We have demonstrated the advantage of the human cytokine-producing animal in
      the maintenance of human HSCs.

PMID- 17512213
TI  - Development of a high-performance MALDI-TOF mass spectrometer utilizing a spiral
      ion trajectory.
AB  - A novel MALDI-TOF mass spectrometer that utilizes a spiral ion trajectory was
      developed. In this mass spectrometer, the ions sequentially passed through four
      toroidal electrostatic sectors and revolved along a figure-eight-shaped orbit on
      a particular projection plane. Each toroidal electrostatic sector had eight
      stories, and during multiple revolutions, the ion trajectory shifted
      perpendicular to the projection plane in every cycle, thereby generating a spiral
      trajectory. The flight path length of one cycle was 2.1 m; therefore, when the
      ions completed eight cycles, the total flight path length was 17 m. By adopting
      an ion optical system that had a flight path length five times longer than that
      in the commonly used reflectron ion optical system, the mass dependence on the
      mass resolving power was reduced, while improving the mass accuracy of the mass
      measurements. The basic performance of the system was tested by using standard
      peptides or the tryptic digest of bovine serum albumin. A mass resolving power of
      80,000 (full width at half maximum) was achieved at m/z = 2564 (ACTH18-39). An
      improved mass accuracy less than 2 ppm was realized over a wide m/z range of 500
      to 3000 by correction using one or two internal standard substances.

PMID- 17512214
TI  - A study of noncovalent protein complexes by matrix-assisted laser
      desorption/ionization.
AB  - A sample preparation method has been developed for detection of noncovalent
      protein-protein complexes by MALDI in this work. An aqueous solution of the
      matrix at pH 7 allows the reproducible detection of a protein dimer, a protein
      tetramer, and a heterodimer. The signals are stable under long irradiation and
      can be detected at wide ranges of concentrations and with different laser
      intensities.

PMID- 17512215
TI  - Traditional and novel risk factors for clinically diagnosed abdominal aortic
      aneurysm: the Kaiser multiphasic health checkup cohort study.
AB  - BACKGROUND: Identification of risk factors for and early diagnosis of clinically
      significant abdominal aortic aneurysm (AAA) before rupture is vital to optimize
      outcomes in these patients. Our aim was to examine traditional and three novel
      potential risk factors (abdominal obesity, white blood cell count, and kidney
      function) for abdominal aortic aneurysm (AAA, comprising discharge diagnosis or
      surgical repair) in a large multiethnic population. METHODS: Cohort study (N
      =104,813) conducted at an integrated health care delivery system in northern
      California. RESULTS: After a median of 13 years, 605 AAA events (490 in men and
      115 in women; 91 [15%] fatal) were observed. In multivariable analysis, factors
      significantly associated with risk of clinically detected AAA included male
      gender, older age, black race (inversely), low educational attainment, cigarette
      smoking (with dose-response relation), height, treated and untreated
      hypertension, high total serum cholesterol, elevated white blood cell count,
      known coronary artery disease, history of intermittent claudication, and reduced
      kidney function. A significant Asian race by gender interaction was found such
      that Asian race had a (borderline significant) protective association with AAA in
      men but not in women. CONCLUSIONS: Our findings confirm that major
      atherosclerotic risk factors, except for diabetes and obesity, are also
      prospectively related to AAA and suggest that elevated white blood cell count and
      reduced kidney function may improve risk stratification for clinically relevant
      AAA.

PMID- 17512216
TI  - Interactions between working memory and visual perception: an ERP/EEG study.
AB  - How do working memory and perception interact with each other? Recent theories of
      working memory suggest that they are closely linked, and in fact share certain
      brain mechanisms. We used a sequential motion imitation task in combination with
      EEG and ERP techniques for a direct, online examination of memory load's
      influence on the processing of visual stimuli. Using a paradigm in which subjects
      tried to reproduce random motion sequences from memory, we found a systematic
      decrease in ERP amplitude with each additional motion segment that was viewed and
      memorized for later imitation. High-frequency (>20 Hz) oscillatory activity
      exhibited a similar position-dependent decrease. When trials were sorted
      according to the accuracy of subsequent imitation, the amplitude of the ERPs
      during stimulus presentation correlated with behavioral performance: the larger
      the amplitude, the more accurate the subsequent imitation. These findings imply
      that visual processing of sequential stimuli is not uniform. Rather, earlier
      information elicits stronger neural activity. We discuss possible explanations
      for this observation, among them competition for attention between memory and
      perception and encoding of serial order by means of differential activation
      strengths.

PMID- 17512217
TI  - A review of micro- and macrovascular analyses in the assessment of tumor
      associated vasculature as visualized by MR.
AB  - There is currently no noninvasive, reliable method of assessing brain tumor
      malignancy or of monitoring tumor treatment response. Monitoring changes to tumor
      vasculature might provide an effective means of assessing both tumor
      aggressiveness and treatment efficacy. To date, most such research has
      concentrated upon tumor "microvascular" imaging, with permeability and/or
      perfusion imaging used to assess vessel changes at the subvoxel level. An
      alternative approach assesses tumor vasculature at the "macroscopic" level,
      calculating the numbers and shapes of the larger vessels discriminable by
      magnetic resonance angiography. This paper provides an overview of magnetic
      resonance (MR) vascular imaging at both the microscopic (dynamic MR perfusion and
      permeability) and macroscopic (MR angiographic) levels. The two approaches
      provide different, complementary information and together could provide important
      insights into cancer growth as well as new methods of assessing malignancy and
      tumor treatment response.

PMID- 17512218
TI  - Multivariate examination of brain abnormality using both structural and
      functional MRI.
AB  - A multivariate classification approach has been presented to examine the brain
      abnormalities, i.e., due to prenatal cocaine exposure, using both structural and
      functional brain images. First, a regional statistical feature extraction scheme
      was adopted to capture discriminative features from voxel-wise morphometric and
      functional representations of brain images, in order to reduce the dimensionality
      of the features used for classification, as well as to achieve the robustness to
      registration error and inter-subject variations. Then, this feature extraction
      method was used in conjunction with a hybrid feature selection method and a
      nonlinear support vector machine for the classification of brain abnormalities.
      This brain classification approach has been applied to detecting the brain
      abnormality associated with prenatal cocaine exposure in adolescents. A promising
      classification performance was achieved on a data set of 49 subjects (24 normal
      and 25 prenatally cocaine-exposed teenagers), with a leave-one-out cross
      validation. Experimental results demonstrated the efficacy of our method, as well
      as the importance of incorporating both structural and functional images for
      brain classification. Moreover, spatial patterns of group difference derived from
      the constructed classifier were mostly consistent with the results of the
      conventional statistical analysis method. Therefore, the proposed approach
      provided not only a multivariate classification method for detecting brain
      abnormalities, but also an alternative way for group analysis of multimodality
      images.

PMID- 17512219
TI  - Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a
      comparison between clinical subtypes and correlations with clinical parameters.
AB  - Multiple system atrophy (MSA) is a neurodegenerative disease affecting basal
      ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal
      cord. Clinically, a cerebellar (MSA-C) and a parkinsonian variant of MSA (MSA-P)
      are distinguished. We used voxel-based morphometry (VBM) and voxel-based
      relaxometry (VBR) in 48 MSA patients (32 MSA-C, 16 MSA-P) and 46 controls. In MSA
      C, VBM revealed gray matter loss in cerebellum, right thalamus, both putamina and
      several cortical regions including insular cortex. Gray matter loss in the
      cerebellum and insular cortex was correlated with disease duration and severity.
      There was white matter loss in the brainstem, which was correlated with disease
      duration and severity. VBR analysis in MSA-C showed decreased relaxation rate R2
      in cerebellum, pontine brainstem and cortical regions including insular cortex.
      In MSA-P, gray matter was reduced in cerebellum, dorsal midbrain, both putamina,
      and several cortical regions including insular cortex. A correlation with disease
      duration and severity was detected only for some small cortical areas. Direct
      comparison of MSA-C and MSA-P showed differences only in infratentorial brain
      regions where structural abnormalities were more pronounced in MSA-C than in MSA
      P. In MSA-C, there was a stronger reduction of gray matter in the basal parts of
      the cerebellum, of white matter in the brainstem and of the relaxation rate R2 in
      the cerebellum and brainstem.

PMID- 17512220
TI  - Neuropathic shoulder in syringomyelia treated with resurfacing arthroplasty of
      humeral head and soft-tissue lining of glenoid: a case report.

PMID- 17512221
TI  - The anteromedial facet of the coronoid process of the ulna.
AB  - Fracture of the anteromedial facet of the coronoid process has been recognized as
      an important type of coronoid fracture. We performed a quantitative analysis of
      21 3-dimensional computed tomography scans to evaluate the degree to which the
      anteromedial facet protrudes as a distinct process separate from the proximal
      ulnar metaphysis. The distance between the center axis of the trochlear notch and
      the most medial edge of the anteromedial facet averaged 12.5 mm (range, 8.7-20.1
      mm). The part of the maximum anteromedial facet width that was supported by the
      proximal ulnar metaphysis and diaphysis averaged 5.4 mm (range, 1.7-11.5 mm). On
      average, 58% of the anteromedial facet (range, 26%-82%) was unsupported by the
      proximal ulnar metaphysis and diaphysis. It is not surprising that this
      relatively vulnerable protrusion from the anteromedial facet of the coronoid is
      frequently a separate fracture fragment in complex traumatic elbow instability.

PMID- 17512222
TI  - Cultural adaptation and validation of a German version of the Arthritis Impact
      Measurement Scales (AIMS2).
AB  - OBJECTIVE: To validate a translated and culturally adapted version of the
      Arthritis Impact Measurement Scale (AIMS) 2 in primary care patients with
      osteoarthritis (OA) of the hip and knee. METHOD: The AIMS2 was translated into
      German and culturally adapted. The questionnaire then was administered to 220
      primary care patients with OA of the knee or hip. Two hundred and nine
      questionnaires were returned and analysed. Test-retest reliability was tested in
      50 randomly selected patients, of those 42 completed the questionnaire after 2
      weeks for a second time. RESULTS: Item-scale correlations were reasonably good as
      well as the discriminative power of separate scales. The assessment of internal
      consistency reliability also revealed satisfactory values; Cronbach's alpha was
      0.77 or higher for all scales. The test-retest reliability, estimated in an
      intraclass correlation coefficient (ICC), exceeded 0.90, except the "social
      activities" scale (0.87). Since only patients with OA of the lower limb were
      enrolled, substantial floor effects occurred in the "arm function" (28.2%) and
      the "hand and finger function" scale (29.2%). The principal factor analysis
      confirmed the postulated three-factor structure with a physical, physiological
      and social dimension, explaining 48.5%, 13.9% and 6.8% of the variation,
      respectively. External validity was assessed by calculating correlations to the
      Western Ontario and MacMaster (WOMAC) osteoarthritis questionnaire a pain visual
      analogue scale (VAS) and the Kellgren score as well as to disease duration.
      Spearman's "R" achieved satisfactory values for the corresponding WOMAC scales
      and the pain-VAS. Correlations with disease duration as well as with the
      radiological grading were low. CONCLUSION: The GERMAN-AIMS2 is a reliable and
      valid instrument to assess the quality of life (QoL) in primary care patients
      suffering from OA.

PMID- 17512223
TI  - Changes in expression of cell wall turnover genes accompany inhibition of
      chromosome segregation by bovine protein kinase C alpha expression in
      Saccharomyces cerevisiae.
AB  - Expression of bovine PKCalpha in Saccharomyces cerevisiae results in growth
      inhibition, which is strongly augmented upon addition of phorbol esters. To
      investigate the nature of this PKC-induced inhibition of cell growth, wildtype
      and bovine PKCalpha-expressing yeast cells were examined by flow cytometry and by
      fluorescence microscopy after staining with propidium iodide. Upon expression and
      activation of the mammalian PKC isoform, cells accumulated in the G2/M phase of
      the cell cycle and exhibited impaired chromsome segregation. In some instances,
      PKC expression and activation was accompanied by a defect in septum formation
      between mother and daughter cells. cDNA microarray analysis revealed 4 genes
      (CTS1, DSE1, DSE2, and SVS1) that changed expression in both a PKCalpha- and
      phorbol ester-dependent manner. These findings were confirmed by quantitative
      real-time PCR. Three of these genes are involved in cell wall turnover and are
      regulated by a single transcription factor (Ace 2) that localizes to daughter
      cell nuclei after cytokinesis. Taken together, these observations suggest that
      expression and activation of bovine PKCalpha in yeast cells repress growth by
      inducing an accumulation of cells in G2/M, likely through an impairment of
      chromosome segregation, cytokinesis, and septum formation. Moreover, when these
      observations are taken in the context of previously published observations with
      various yeast null mutants, we propose that bovine PKCalpha may directly or
      indirectly activate a subunit of the PP2A phosphatase complex (cdc55), which is a
      component of the mitotic spindle checkpoint.

PMID- 17512224
TI  - Genetic homogeneity/heterogeneity of Propionibacterium acnes isolated from
      patients during cardiothoracic reoperation.
AB  - Following cardiothoracic surgery, deep sternal wound infection (SWI) remains one
      of the most severe complications. Recently, Propionibacterium acnes has been
      suspected as an etiological agent of deep SWI. However, this bacterium
      constitutes part of the resident micro-flora of the human skin. Consequently,
      findings of P. acnes in invasive samples are difficult to value. The aims of this
      study were to develop and optimize a pulsed-field gel electrophoresis (PFGE)
      protocol for P. acnes, in order to investigate the genetic
      homogeneity/heterogeneity of P. acnes isolates from multiple tissue samples
      (predominantly biopsies), collected at different locations, from 12 patients
      during cardiothoracic reoperation. There were 24 distinguishable PFGE
      fingerprints identified among the P. acnes isolates (n=54). Five (42%) of the
      patients carried only isolates that were interpreted as presumably clonally
      related. From the remaining seven patients, two or three different P. acnes
      clones were cultured, however, from six of them, the clones were identified in
      multiple samples. P. acnes may be a relatively frequent etiological agent of
      postoperative cardiothoracic infections. Existence of several clonally related P.
      acnes isolates derived from multiple samples from patients suffering from deep
      SWI after cardiothoracic surgery has not previously been shown.

PMID- 17512225
TI  - Clostridium symbiosum as a cause of bloodstream infection in an immunocompetent
      patient.
AB  - Bloodstream infection caused by Clostridium symbiosum was previously reported in
      only one case, from a highly immunocompromised patient with metastic colon
      cancer. We describe the second case of clinical bacteraemic sepsis caused by C.
      symbiosum from a previously healthy man, which underlines the pathogenicity of
      this species.

PMID- 17512226
TI  - Randomised trial of polytetrafluoroethylene patch insertion for recurrent great
      saphenous varicose veins.
AB  - OBJECTIVES: The aim of this study was to assess the possible value of a
      polytetrafluoroethylene (PTFE) patch in the treatment of recurrent varicose
      veins. METHODS: Thirty-one patients (40 legs) with recurrent saphenofemoral
      junction incompetence were randomised to redo saphenofemoral ligation and great
      saphenous vein stripping with, or without the insertion of a PTFE patch over the
      ligated junction. Patients underwent assessment preoperatively, and at 6 weeks, 1
      year and 2 years postoperatively with clinical examination, duplex imaging and
      completion of the Aberdeen Varicose Vein Symptom Severity Score (AVVSSS).
      RESULTS: A total of 27 patients (32 legs) attended for assessment at 6 weeks, 25
      patients (30 legs) at 1 year and 27 patients (32 legs) at 2 years. At 6 weeks,
      seven legs (22%) had an area of cutaneous numbness; all but one had resolved by 1
      year. Four legs (13%) developed a groin infection, which required antibiotics, 2
      had a groin haematoma and four had a seroma, all of which resolved spontaneously.
      The overall complication rate was 35% (11 legs), with no statistically
      significant difference between the groups. Four of 16 legs without a patch and
      five of 16 legs with a patch developed neovascularisation at the saphenofemoral
      junction on duplex imaging by two years postoperatively. Two cases of
      neovascularisation in the patch group and one in the no patch group directly
      resulted in clinical recurrence (p=1.0). There was an improvement in patients'
      AVVSSS two years postoperatively (p<0.03), that was similar in both groups.
      CONCLUSIONS: In this study, insertion of a PTFE patch did not affect the rate of
      perioperative complications and it did not appear to contain neovascularisation.

PMID- 17512227
TI  - Towards a molecular genetic system for the pathogenic fungus Paracoccidioides
      brasiliensis.
AB  - We herein report the development of a molecular toolbox for the dimorphic fungus
      Paracoccidioides brasiliensis, specifically a more efficient transformation and a
      gene expression system. We evaluated several parameters that influence
      Agrobacterium tumefaciens-mediated transformation (ATMT), such as co-cultivation
      conditions and host cell susceptibility. Our results show that cellular recovery
      and air drying of A. tumefaciens:P. brasiliensis mixtures are essential for ATMT.
      Overall, our data indicate a transformation efficiency of 78+/-9 transformants/co
      cultivation (5+/-1 transformants/10(6) target cells). P. brasiliensis GFP
      expressing isolates were also constructed by insertion of the GFP gene under the
      control of several fungal promoters. RT-PCR, epifluorescence microscopy and flow
      cytometry analysis revealed Gfp visualization for all studied promoters but
      without significant differences in fluorescence and gene expression levels.
      Moreover, we present evidence for the occurrence of random single gene copy
      integration per haploid nuclei and the generation of homokaryon progeny, relevant
      for the future use in targeted mutagenesis and linking mutations to phenotypes.

PMID- 17512228
TI  - Validity and reliability of the Children's Visual Function Questionnaire (CVFQ).
AB  - PURPOSE: The Children's Visual Function Questionnaire (CVFQ) is a vision-specific
      quality-of-life instrument designed for use with children up to 7 years of age.
      The goal of this study was to assess the construct validity of CVFQ subscales by
      examining their sensitivity to four research questions commonly posed in
      ophthalmic clinical trials. METHODS: CVFQ Competence, Personality, Family Impact,
      and Treatment Difficulty subscale scores were compared for groups of pediatric
      patients with unilateral versus bilateral disease (35 bilateral and 38 unilateral
      cataract), different severity of visual impairment (61 retinopathy of prematurity
      [ROP] grouped by acuity), difficulty of treatment regimen (22 optical, 44
      surgery, 38 surgery with optical, and 35 surgery with optical and occlusion), and
      alternative treatments for the same condition (24 intraocular lenses, 37 aphakic
      contact lenses). RESULTS: Patients treated for bilateral cataracts had
      significantly worse Competence subscale scores than patients treated for
      unilateral cataract, and patients with bilateral severe ROP (visual acuity 20/200
      or poorer in both eyes) had significantly worse Competence subscale scores than
      other patients with ROP. Treatment Difficulty subscale scores were worse for
      patients with unilateral cataracts than for those with bilateral cataracts, worse
      for patients treated with occlusion therapy than for those treated with surgery
      or optical correction, and worse for those treated with an aphakic contact lens
      than for those treated with an intraocular lens. Family Impact subscale scores
      were worse for patients with unilateral cataracts than for those with bilateral
      cataracts, worse for patients treated with surgery than for those treated with
      optical correction, and worse for those with severe bilateral ROP than for any
      other patients with ROP. CONCLUSIONS: The CVFQ subscales quantified meaningful
      differences among pediatric patient groups who were chosen to address key
      research questions commonly posed in ophthalmic clinical trials.

PMID- 17512229
TI  - A case of Sturge-Weber syndrome in association with phacomatosis
      pigmentovascularis and developmental glaucoma.
AB  - Sturge-Weber syndrome is a rare neurocutaneous disorder characterized by a facial
      nevus flammeus and extensive angiomatous changes involving the leptomeninges, the
      dura, and vessels of the gray and white matter. Oculodermal melanocytosis is
      characterized by hyperpigmentation of the facial skin in the distribution of the
      ophthalmic, maxillary, and occasionally mandibular division of the trigeminal
      nerve.

PMID- 17512230
TI  - Acute retinal necrosis as a late sequela of herpes simplex type 1 encephalitis in
      a child.
AB  - Herpes simplex virus (HSV) is a common infection that occasionally presents with
      destructive lesions. Two of the most feared presentations of HSV are encephalitis
      and acute retinal necrosis. Although there are numerous reports of acute retinal
      necrosis presenting after HSV-2 infection in children, it has been rarely
      reported in children after HSV-1 infection. Herein we report a child who
      developed acute retinal necrosis 17 months after HSV-1 encephalitis.

PMID- 17512231
TI  - Recovery from blood alkalosis in the Pacific hagfish (Eptatretus stoutii):
      involvement of gill V-H+-ATPase and Na+/K+-ATPase.
AB  - To investigate the base secretory mechanisms in the Pacific hagfish (Eptatretus
      stoutii), we injected animals with NaHCO3 into the subcutaneous sinus. In the
      first series of experiments, hagfish were injected with 6000 micromol kg(-1)
      NaHCO3 (base-infused hagfish, BIH) or NaCl (controls). Blood pH increased
      significantly 1 h after injection in BIH (8.05+/-0.05 vs. 7.82+/-0.03 pH units),
      but returned to control values by t=6 h. Plasma total CO2 (TCO2) followed the
      same pattern. Immunolabeled sections revealed that Na+/K+-ATPase and V-H+-ATPase
      were usually located in the same cells. Western blotting revealed that the
      abundance of both proteins remained unchanged in whole gill homogenates and in a
      fraction enriched in cell membranes 6 h after the injections. The second
      experimental series was to induce long-term alkalosis by serially injecting 6000
      micromol kg(-1) NaHCO3 every 6 h for 24 h. Blood pH completely recovered from the
      base loads within 6 h after each injection. Moreover, plasma TCO2 was not
      elevated 3 h after the second infusion, suggesting that HCO3(-) secreting
      mechanisms had been upregulated by that time. Na+/K+-ATPase and V-H+-ATPase
      cellular localizations did not change in the 24 h base infusion protocol. Na+/K+
      ATPase abundance was similar in gill homogenates from fish from both treatments.
      However, Na+/K+-ATPase abundance in the membrane fraction was significantly lower
      in BIH, while V-H+-ATPase was greater both in whole gill and membrane fractions.
      Our results suggest that differential insertion of V-H+-ATPase and Na+/K+-ATPase
      into the basolateral membrane is involved in recovering from alkalotic stress in
      hagfish.

PMID- 17512232
TI  - Short-term recombinant human growth hormone administration improves respiratory
      function in abstinent anabolic-androgenic steroid users.
AB  - OBJECTIVES: To determine whether 6 days recombinant human growth hormone (rhGH)
      administration, in an abstinent anabolic-androgenic steroid (AAS) using group had
      any respiratory, endurance exercise and biochemical effects compared with an
      abstinent AAS control group. METHODS: Male subjects (n=48) were randomly divided,
      using a single blind procedure into two groups: (1) control group (C) n=24,
      means+/-SD, age 32+/-11 years; height 1.8+/-0.06 m; (2) rhGH using group (0.019
      mg kg(-1) day(-1)) (GH) n=24, means+/-SD, age 32+/-9 years; height 1.8+/-0.07 m.
      Anthropometry, respiratory muscle function and endurance exercise were
      investigated. Respiratory measurements examined, were forced expiratory volume in
      one second, forced vital capacity, maximum inspiratory pressure and maximum
      expiratory pressure. Endurance exercise was assessed by measuring peak oxygen
      uptake (VO(2)peak). Biochemical analysis included; haemoglobin, packed cell
      volume, glucose, sodium, urea, creatinine, total protein, albumin, testosterone
      and insulin like growth factor-I (IGF-I). RESULTS: Forced expiratory volume in
      one second/forced vital capacity, maximum inspiratory pressure, maximum
      expiratory pressure, and IGF-I significantly increased compared with the control
      group (all P<0.05). Body mass index, fat free mass index, peak oxygen uptake,
      maximum inspiratory pressure, maximum expiratory pressure, IGF-I and serum sodium
      significantly increased, whilst body fat, total protein and albumin,
      significantly decreased within the GH group (all P<0.017). CONCLUSION: The
      findings of this study indicated that short-term high dose rhGH increased aerobic
      performance and respiratory muscle strength in former AAS users.

PMID- 17512233
TI  - Increase in congenital hypothyroidism in New York State and in the United States.
AB  - Mandated screening of newborns for congenital hypothyroidism (CH) in NYS was
      initiated in l978. Currently, every newborn screening program in the U.S.
      includes CH in its panel. Between 1978 and 2005, 7.4 million newborns were
      screened for CH in NYS. In NYS, between 1978 and 2005, the incidence of CH has
      increased by 138%. Nationwide (excluding NYS data), with nearly 58 million
      infants screened between 1987 and 2002, the incidence has increased 73% between
      1987 and 2002. These data and possible reasons for the increases are discussed,
      though no definitive causes are identified.

PMID- 17512234
TI  - Rate and predictors of optimal virologic response to antiretroviral therapy in
      Colombia.
AB  - OBJECTIVE: To estimate the rate of optimal response to antiretroviral therapy and
      its predictors in Colombia. METHODS: A retrospective cohort study was performed.
      The medical records of all patients at three major HIV clinics in different areas
      of Colombia, South America, were reviewed. Eligible patients met the following
      criteria: (1) viral load test available while on therapy; and (2) patients must
      have been on a stable first antiviral regimen for at least 1 year (48 weeks).
      Optimal virologic response was defined as a viral load <400 copies/ml. RESULTS:
      Two hundred and twenty patients were eligible for the study. The optimal
      virologic response rate was 40% (95% confidence interval 34-46%). Younger age
      (p=0.02) and western region of the country (p=0.026) were the only significant
      predictors of non-optimal response in bivariate analysis. Multivariate logistic
      regression analysis confirmed younger age (p=0.0054) and geographic area
      (p=0.0468) as independent predictors of non-optimal response. CONCLUSIONS: The
      optimal response rate in some areas of Colombia seems lower than that reported
      for other areas of the developing world. Poorer virologic responses were observed
      in younger patients and in those from the western region of the country.

PMID- 17512235
TI  - Large scale blood group genotyping.
AB  - Determination of predicted blood group phenotype by determination of genotype has
      been performed since the 1990s. This evolved due to the rapid accrual of
      information surrounding the molecular basis of blood group antigen expression,
      which started in 1990 with ABO and RH systems and has now resulted in the
      molecular description of 28 of the 29 blood groups. Blood group genotyping is
      currently performed mostly for fetal blood group incompatibility and for
      assessment of multi-transfused patients. Both of these clinical scenarios are
      either dangerous or technically difficult, respectively to define serologically.
      With the simultaneous development of mass scale genotyping platforms it has now
      permitted the application of them to blood group genotype determination. In this
      paper, I describe some recently published work that has demonstrated that mass
      scale genotyping approaches are feasible. These approaches may lead to more
      effective management of blood stocks and patient cross-matching by reducing the
      dependence on serology during the time critical pre-transfusion phase. It is most
      probable that large scale studies, perhaps involving many European Union and
      North American based blood suppliers, may drive the introduction of this
      technology and convince red cell serologists that this approach may allow their
      work to be more focussed.

PMID- 17512236
TI  - [TVT-O treatment of stress urinary incontinence: immediate and one-year results].
AB  - OBJECTIVE: To compare one-year results between the classic retropupubic (TVT) and
      the in-out transobturator approaches (TVT-O) of tension-free vaginal tape for the
      treatment of stress urinary incontinence (SUI). PATIENTS AND METHODS: The first
      82 patients operated for SUI by TVT-O in our institution were included in the
      analysis. Patients were evaluated at 1 and 12 months. The global satisfaction
      rate was assessed at 12 months by a self-reported questionnaire. Results were
      compared to those of the first 124 patients operated of SUI by TVT in the same
      institution and by the same surgeons between 1996 and 1999. RESULTS: Except a
      younger mean age in the TVT-O group (57 versus 60 years), no other preoperative
      parameter was significantly different between the TVT and the TVT-O groups. The
      mean operating time was shorter in the TVT-O group (15 versus 30 minutes,
      P<0.001). No intraoperative complication occurred. The rate of bladder
      perforation was significantly lower in the TVT-O group (0 versus 8.8%, P=0.004).
      The rate of post-voiding residual less than 100 ml was higher in the TVT-O group
      (88 versus 61%, P<0.001). In the TVT-O group, 40% of patients had postoperative
      inguinal pain (mean=9 days, range 2-15 days). After 12 months from TVT-O, 85% of
      patients were completely dry, 6% had de novo over bladder activity, and 93.5% of
      patients were satisfied with the treatment they received. The 12-month results
      were not significantly different between the TVT and the TVT-O groups. DISCUSSION
      AND CONCLUSION: With a follow-up of 12 months, TVT-O is as efficient as TVT and
      has a lower risk of bladder injury, a cut by half operating time, and less
      postoperative dysuria.

PMID- 17512237
TI  - [Management of an ovarian stimulation in case of a Kallmann-De Morsier syndrome.
      The role of LH].
AB  - We report a case of ovarian stimulation in a woman with a Kallmann-De Morsier
      syndrome, which resulted in a triple pregnancy and childbirth by caesarean
      section at 36 weeks of amenorrhea of three girls weighing from 1,950 to 2,300 g.
      Starting from a literature review of Kallmann-De Morsier syndrome, we discuss the
      role of LH during the follicular phase and the monitoring of ovarian stimulation.

PMID- 17512238
TI  - Management of neovascular age-related macular degeneration.
AB  - Neovascular age-related macular degeneration (AMD) is becoming an increasing
      socio-medical problem as the proportion of the aged population is continuously
      increasing. However, new insights in the pathogenesis of the disease offer the
      opportunity to develop targeted therapies that attack the disease process more
      successfully than ever. This review article will focus on summarizing the actual
      options in the management of neovascular AMD and provide a short overview about
      recent therapeutic options in clinical and preclinical evaluation. The recent
      development of anti-VEGF substances for use in clinical routine has markedly
      improved the prognosis of patients with neovascular AMD. Intravitreal treatment
      with substances targeting all isotypes of vascular endothelial growth factor
      (VEGF), for the first time in the history of AMD treatments, results in a
      significant increase in visual acuity in patients with neovascular AMD. Overall,
      anti-angiogenic approaches provide vision maintenance in over 90% and substantial
      improvement in 25-40% of patients. The combination with occlusive therapies like
      photodynamic therapy (PDT) potentially offers a reduction of re-treatment
      frequency and long-term maintenance of the treatment benefit. Further
      developments interacting with various steps in the angiogenic cascade are under
      clinical or preclinical evaluation and may soon become available. Nevertheless,
      the growing number of novel therapeutic options will have to provide proof of
      concept in randomized controlled clinical trials, a major challenge in view of
      the rapidly evolving field. For those therapies, which are already in clinical
      use, reasonable diagnostic tools for follow-up need to be developed, as the
      burden of continuous clinical monitoring of all patients and all indications is
      significant for patients and doctors. Ultimately, economic issues will be the
      limiting factor for the clinical availability of different treatment options.

PMID- 17512239
TI  - Chagas cardiomyopathy (Trypanosoma cruzi): does prolactin play a role?

PMID- 17512240
TI  - Role of fibroblast growth factor 8 in growth and progression of hormonal cancer.
AB  - Hormonal cancers such as breast and prostate cancer arise from steroid hormone
      regulated tissues. In addition to breast and prostate cancer hormonal regulation
      has also a role in endometrial, ovarian, testis and thyroid carcinomas. The
      effects of estrogens, androgens and progestagens on tumor growth are largely
      mediated by paracrine and autocrine target molecules which include growth factors
      and growth factor receptors. During cancer progression the hormonal growth
      regulation is often lost or overcome by an inappropriate activation of growth
      factor signaling cascades. One of the growth factors which have been associated
      with the regulation of growth and progression of hormonal cancer is fibroblast
      growth factor 8 (FGF8) which has also been recognized as an oncogene. FGF8 is
      widely expressed during embryonic development. It has been shown to mediate
      embryonic epithelial-mesenchymal transition and to have a crucial role in
      gastrulation and early organization and differentiation of midbrain/hindbrain,
      pharyngeal, cardiac, urogenital and limb structures. During adulthood FGF8
      expression is much more restricted but in hormonal cancers it becomes frequently
      activated. High level of FGF8 expression in tumors is associated with a poor
      prognosis at least in prostate cancer. In experimental models FGF8 induces and
      facilitates prostate tumorigenesis and increases growth and angiogenesis of
      tumors. Several lines of evidence for autocrine and paracrine loops in the growth
      regulation of breast, prostate and ovarian cancer by FGF8 have been suggested.

PMID- 17512241
TI  - In vivo photochemical skin micronucleus test using a sunlight simulator:
      detection of 8-methoxypsoralen and benzo[a]pyrene in hairless mice.
AB  - Evaluating in vivo photochemical genotoxicity (photogenotoxicity) or
      photochemical carcinogenicity (photocarcinogenicity) in the skin that is actually
      exposed to light is important for estimating the risk of human exposure to
      chemicals under sunlight. With regard to the skin micronucleus test, Nishikawa et
      al. developed a reliable technique that is simple and in which the negative
      control has a stable background. In the present study, we applied 8
      methoxypsoralen (8-MOP) and benzo[a]pyrene (B[a]P) to the backs of hairless mice
      and subjected the mice to irradiation by a sunlight simulator in order to
      investigate whether this test can detect photogenotoxicity of these chemicals. In
      the treatment with 8-MOP [0.00075% and 0.0015% (w/v)], a significant increase was
      observed in the frequency of micronucleated cells only under light irradiation
      using the sunlight simulator. At a high chemical dose, the frequency of
      micronucleated cells increased from 48h after the treatment, peaked at 96h, and
      then decreased at 168h. Furthermore, at 96h with the high dose under light
      irradiation, we frequently observed cells with nuclear buds. In the treatment
      with B[a]P [first experiment: 0.025% and 0.05% (w/v); second experiment: 0.005%,
      0.01%, and 0.02% (w/v)], a significant increase was observed in the frequency of
      micronucleated cells at skin-irritating doses [0.01%, 0.02%, 0.025%, and 0.05%
      (w/v)] at 72 or 96h after the treatment only under light irradiation using the
      sunlight simulator. In conclusion, photogenotoxicity of 8-MOP and B[a]P was
      detected in the in vivo photochemical skin micronucleus study.

PMID- 17512242
TI  - Vibrational spectra and assignments of 3-aminobenzyl alcohol by ab initio Hartree
      Fock and density functional method.
AB  - In this work, we will report a combined experimental and theoretical study on
      molecular and vibrational structure of 3-aminobenzyl alcohol. The FT-Raman and FT
      IR spectra of 3-aminobenzyl alcohol were recorded in the solid phase. The
      equilibrium geometry, harmonic vibrational frequencies, infrared intensities,
      Raman scattering activities, depolarization ratios and reduced masses were
      calculated by ab initio HF and density functional B3LYP method with 6-311+G(d,p)
      basis sets. 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 interpretation of the infrared and Raman spectra of 3-aminobenzyl
      alcohol is reported. The theoretical spectrograms for FT-IR spectra of the title
      molecule have been constructed.

PMID- 17512243
TI  - Spectroscopic investigation of conjugated polymers derived from nitroanilines.
AB  - For the first time, the resonance Raman spectroscopy was used to characterize
      polymers derived from meta- and para-nitroanilines. In order to improve the
      polymer structure analysis, other techniques were also used such as FTIR, UV-vis,
      XRD, XPS, EPR and N K-XANES. The insertion of strong electron-withdrawing groups
      (NO2) in polyaniline (PANI)-like backbone causes drastic changes in the lower
      energy charge transfer states, related to the polymer effective conjugation
      length. The resonance Raman data show that the NO2 moiety has a minor
      contribution on the CT state in poly(meta-nitroaniline), PMN, while in the
      poly(para-nitroaniline), PPN, the quinoid structure induced by para-substitution
      increases the charge density of NO2 groups, causing a more localized chromophore.
      The characterization of the imine nitrogen and of the protonated segments was
      done by XPS, N K-XANES and EPR spectroscopies and the lower polymerization degree
      of PPN, in comparison to PMN, is confirmed by XRD and TG data.

PMID- 17512244
TI  - Synthesis, characterization and thermal studies on metal complexes of new azo
      compounds derived from sulfa drugs.
AB  - Four new azo ligands, L1 and HL2-4, of sulfa drugs have been prepared and
      characterized. [MX(2)(L1)(H(2)O)(m)].nH(2)O; [(MX(2))(2)(HL2 or
      HL3)(H(2)O)(m)].nH(2)O and [M(2)X(3)(L4)(H(2)O)].nH(2)O; M=Co(II), Ni(II) and
      Cu(II) (X=Cl) and Zn(II) (X=AcO); m=0-4 and n=0-3, complexes were prepared.
      Elemental and thermal analyses (TGA and DTA), IR, solid reflectance spectra,
      magnetic moment and molar conductance measurements have accomplished
      characterization of the complexes. The IR data reveal that HL1 and HL2-3 ligands
      behave as a bidentate neutral ligands while HL4 ligand behaves as a bidentate
      monoionic ligand. They coordinated to the metal ions via the carbonyl O, enolic
      sulfonamide S(O)OH, pyrazole or thiazole N and azo N groups. The molar
      conductance data reveal that the chelates are non-electrolytes. From the solid
      reflectance spectra and magnetic moment data, the complexes were found to have
      octahedral, tetrahedral and square planar geometrical structures. The thermal
      behaviour of these chelates shows that the water molecules (hydrated and
      coordinated) and the anions are removed in a successive two steps followed
      immediately by decomposition of the ligand in the subsequent steps. The
      activation thermodynamic parameters, such as, E*, DeltaH*, DeltaS* and DeltaG*
      are calculated from the TG curves applying Coats-Redfern method.

PMID- 17512245
TI  - Diacylglycerol kinases: why so many of them?
AB  - Diacylglycerol (DAG) kinase (DGK) modulates the balance between the two signaling
      lipids, DAG and phosphatidic acid (PA), by phosphorylating DAG to yield PA. To
      date, ten mammalian DGK isozymes have been identified. In addition to the C1
      domains (protein kinase C-like zinc finger structures) conserved commonly in all
      DGKs, these isoforms possess a variety of regulatory domains of known and/or
      predicted functions, such as a pair of EF-hand motifs, a pleckstrin homology
      domain, a sterile alpha motif domain and ankyrin repeats. Beyond our
      expectations, recent studies have revealed that DGK isozymes play pivotal roles
      in a wide variety of signal transduction pathways conducting development, neural
      and immune responses, cytoskeleton reorganization and carcinogenesis. Moreover,
      there has been rapidly growing evidence indicating that individual DGK isoforms
      exert their specific roles through interactions with unique partner proteins such
      as protein kinase Cs, Ras guanyl nucleotide-releasing protein, chimaerins and
      phosphatidylinositol-4-phosphate 5-kinase. Therefore, an emerging paradigm for
      DGK is that the individual DGK isoforms assembled in their own signaling
      complexes should carry out spatio-temporally segregated tasks for a wide range of
      biological processes via regulating local, but not global, concentrations of DAG
      and/or PA.

PMID- 17512246
TI  - Comparison of sleep parameters at titration and subsequent compliance between
      CPAP-pretreated and non-CPAP-pretreated patients with obstructive sleep apnea.
AB  - BACKGROUND AND PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS)
      patients undergo continuous positive airway pressure (CPAP) treatment for the
      first time on titration night, and then the effect of overnight CPAP treatment is
      estimated immediately. The purpose of this study is to compare the effects of
      CPAP-pretreated and non-pretreated on patients with OSAHS. METHODS: Prospective
      randomized, controlled parallel study was performed. Seventy patients with OSAHS
      received autoadjusted CPAP treatment for 2 months and then received the standard
      manual titration (CPAP-pretreated group). The other 70 did not receive any CPAP
      treatment before receiving the standard manual titration (non-CPAP-pretreated
      group). RESULTS: The CPAP-pretreated group had significantly improved sleep
      efficiency and arousal index in non-rapid eye movement (NREM) sleep compared with
      the initial CPAP group at titration, whereas there were no significant
      differences between the two groups in other sleep parameters. Eight patients in
      the non-CPAP-pretreated group discontinued CPAP treatment 9 months after the
      titration, whereas one patient in the CPAP-pretreated group discontinued
      treatment. CONCLUSIONS: A preceding CPAP treatment showed minimal effects on
      sleep parameters on titration night and subsequent CPAP compliance rate, although
      it was speculated that this preceding treatment might be of benefit for better
      compliance in some patients.

PMID- 17512247
TI  - Management of obstructive sleep apnea in patients with congenital heart disease
      and Fontan procedures.

PMID- 17512248
TI  - Early and late results of combined mitral-aortic valve surgery.
AB  - OBJECTIVE: This retrospective study was designed to assess the early morbidity
      and mortality as well as long-term mortality of combined aortic-mitral valve
      procedures at a single centre. METHODS: Patients were identified by analysing the
      intensive care and perfusion databases, from 1989 to 2003, with 113 receiving
      aortic-mitral valve procedures. Eighty-four percent of patients received a
      mechanical bileaflet valve. Survival was assessed using a Kaplan-Meier method,
      and determinants of survival with the Cox proportional hazards model. RESULTS:
      There were 57 men and 56 women, median age 59 (18-84) years. The 30-day mortality
      was 9% (n=10). This cohort contained a number of high risk patients, 38% were
      classified as New York Heart Association class IV, 33.5% had at least moderate
      ventricular impairment, 20% were redo procedures and 17% urgent procedures.
      Survival estimates at 5 and 10 years were 85% (0.76-0.90) and 65% (0.49-0.77),
      respectively. Multivariate pre-operative predictors of death included renal
      dysfunction (creatinine >200 micromol/L) and hypertension. Rheumatic aetiology
      was associated with improved survival. CONCLUSION: This study shows acceptable
      short and long-term survival in patients undergoing combined aortic-mitral valve
      surgical procedures at a single centre. Renal impairment and hypertension were
      associated with a poorer long-term prognosis and rheumatic aetiology was
      associated with improved survival. Age, LVEF and NYHA class were not associated
      with a worse outcome. This may affect future decision making in light of an aging
      population.

PMID- 17512249
TI  - High resolution spiral CT scan in the diagnosis of pseudoaneurysm of ascending
      aorta.
AB  - Pseudoaneurysms of the ascending aorta are rare (<1%), and extremely rare from
      aortic vent site, but can be a lifethreatening complication. The basic methods of
      diagnosis are computed tomography scan and aortography. We report high resolution
      spiral CT may provide the best less invasive means in the diagnosis of the
      pseudoaneurysm of the ascending aorta originated from the aortic vent site.

PMID- 17512250
TI  - Intrapericardial haematoma: a rare cause of congestive cardiac failure after
      three years of coronary artery bypass grafting.
AB  - We present a rare case of organised intrapericardial haematoma after three years
      of coronary artery bypass grafting. Delayed cardiac tamponade after open heart
      surgery usually occurs within first few weeks of surgery. Intrapericardial
      organised haematoma causing localised compression of cardiac chambers after three
      years of open heart surgery is very rare. Under cardiopulmonary bypass and
      cardioplegic cardiac arrest, we removed the haematoma. It is difficult to make a
      clinical diagnosis. However once diagnosis is made and haematoma removed, it
      gives good symptomatic relief to the patient.

PMID- 17512251
TI  - Anticipating an altered appearance: women undergoing chemotherapy treatment for
      breast cancer.
AB  - Chemotherapy treatment for cancer can have a profound impact on appearance, and
      is often experienced as distressing. Few qualitative studies explore experiences
      of chemotherapy, and seldom focus on the process of anticipation and preparation
      for an altered appearance. We report findings from an interview study of 19 women
      which explored their expectations of chemotherapy-induced hair loss, their
      anticipated reactions to hair loss and how women intend to prepare for an altered
      appearance. The results demonstrate that women are active in anticipating hair
      loss and adopt a range of different strategies to manage their alopecia--even
      before it has occurred. Four key themes were identified: (a) anticipating hair
      loss, (b) coming to terms with the inevitability of hair loss, (c) becoming
      ready, and (d) taking control. We argue that this can be seen as a form of
      anticipatory coping, which involves affective and behavioural rehearsal so that
      women can feel more in control of their experience of the side effects of
      chemotherapy treatment for cancer. We suggest seeing these activities as a form
      of anticipatory coping, and understanding the psychological reasons why women
      engage in these activities, may help nursing professionals to better support
      women through this often traumatic time.

PMID- 17512252
TI  - The dog that did not bark: malaria vaccines without antibodies.
AB  - To date, the only pre-blood stage vaccine to confer protection against malaria in
      field trials elicits both antigen-specific antibody and T-cell responses. Recent
      clinical trials of new heterologous prime-boost malaria vaccine regimens using
      DNA, fowlpox or MVA, have chiefly elicited T-cell responses that have promisingly
      reduced hepatic merozoites in challenge trials, but failed to protect in field
      trials. These encouraging results suggest further augmentation of T-cell
      responses to pre-blood stage antigens might one day contribute to a highly
      protective vaccine. We envision that a highly protective pre-erythrocytic vaccine
      will likely be based upon a heterologous prime-boost regimen that induces both
      appropriate T-cell responses as well as robust and protracted antibody
      production.

PMID- 17512253
TI  - The opposite-direction modulation of CD4+CD25+ Tregs and T helper 1 cells in
      acute coronary syndromes.
AB  - Different subsets of T lymphocytes have different functions in atherosclerosis
      advancement. T helper 1 cells and T regulatory 1 cells have been demonstrated to
      play opposite roles in rupture of atherosclerotic lesion. However, the role of
      novel subset of T regulatory cells, known as CD4+CD25+Foxp3+ T cells, remains
      largely unknown in coronary artery disease (CAD). In this study, we investigated
      the peripheral CD4+CD25+Foxp3+ T cells of patients with CAD and controls. The
      patients submitted were divided into three groups: stable angina pectoris (SA)
      group, unstable angina pectoris (UA) group and acute myocardial infarction (AMI)
      group. We analyzed the frequencies of peripheral CD4+CD25+Foxp3+ T cells and T
      helper 1/T helper 2 cells, expression of Foxp3 in CD4+CD25+ T subsets and
      cytokines pattern in patients and controls. We found that the reduction of
      CD4+CD25+Foxp3+ T lymphocytes was consistent with the expansion of Th1 cells in
      patients with unstable CAD. The reversed development between CD4+CD25+ Tregs and
      Th1 cells might contribute to plaque destabilization.

PMID- 17512254
TI  - Asymptomatic trichomonas and candida colonization and pregnancy outcome.
AB  - Trichomonas vaginalis is a sexually transmitted surface pathogen of the lower
      urogenital tract, and may be associated with asymptomatic vaginal colonization or
      intensely symptomatic vaginitis. In pregnancy it is associated with an increased
      risk of preterm delivery. However, a randomized trial of treatment of
      asymptomatic trichomonas colonization in pregnancy showed an increase in the risk
      of preterm delivery in treated women. The reasons for this paradox are yet to be
      fully elucidated. Candida species, on the other hand, may be present--usually in
      the yeast form--in the vaginal flora of up to 40% of healthy pregnant women.
      Although candidiasis is not usually associated with chorioamnionitis or preterm
      delivery, there is some emerging evidence to suggest that screening for and
      eradication of candida during pregnancy may reduce the risk of preterm delivery.
      This chapter reviews the impact of these common vaginal infections on pregnancy
      outcome and appraises the recent evidence on the role of treatment during
      pregnancy.

PMID- 17512255
TI  - Role of antibiotic therapy for bacterial vaginosis and intermediate flora in
      pregnancy.
AB  - Bacterial vaginosis and intermediate flora are associated with late miscarriage
      and preterm delivery. The mechanisms involved are not yet fully understood.
      Clinical trials of antibiotic therapy to reduce these complications have yielded
      conflicting results. These trials, however, were conducted in mixed populations
      of pregnant women with variable risk profiles for preterm delivery. Furthermore,
      investigators used different criteria for diagnosis, treated with different
      antibiotics at different doses and via different routes, and initiated treatment
      at different gestational ages. Over 80% of pregnant women with abnormal vaginal
      flora have a good outcome, and in some populations the presence of bacterial
      vaginosis is not associated with preterm delivery, suggesting that other host
      factors may modify the risk. Recent studies have examined the roles of genetic
      regulation of host immune response, bacterial pathogenic factors, and enzymes in
      the vagina, and how these factors interact to drive a given outcome. These
      markers have the potential to better define the women at maximal risk and
      therefore guide future interventions. This chapter aims to appraise the current
      state of treatment of abnormal vaginal flora in pregnancy and suggest appropriate
      management based on the available evidence.

PMID- 17512257
TI  - Alpha1-adrenergic receptors augment P2X3 receptor-mediated nociceptive responses
      in the uninjured state.
AB  - In the present study, the adrenergic receptor (AR) subtype mediating adrenergic
      augmentation of P2X(3) receptor-mediated nociceptive responses on sensory nerve
      endings was examined by using selective AR receptor agonists and antagonists in
      Sprague Dawley rats in the uninjured state. Local administration of alphabeta
      methyleneATP (ligand for P2X3/P2X2/3 receptors) into the plantar hind paw
      produced few pain behaviors when given alone in this strain of rats; combination
      with adrenaline (alpha1- and alpha2-AR agonist) and phenylephrine (alpha1-AR
      agonist) but not clonidine or UK 14,304 (alpha2-AR agonists) increased flinching
      behaviors. Flinching produced by noradrenaline (NA)/alphabeta-methyleneATP was
      suppressed by low doses of prazosin (alpha1-AR antagonist), and this reduction
      was selective compared with yohimbine (alpha2-AR antagonist). Prazosin also
      reduced flinching produced by phenylephrine/alphabeta-methyleneATP. Using thermal
      threshold determinations, adrenaline and phenylephrine but not clonidine or UK
      14,304, mimicked the action of NA in augmenting reductions in thermal thresholds
      produced by alphabeta-methyleneATP. Terazosin (another alpha1-AR antagonist)
      inhibited hyperalgesia produced by NA/alphabeta-methyleneATP. These results
      provide evidence for alpha1-AR involvement in adrenergic augmentation of
      P2X3/P2X2/3 receptor-mediated responses on sensory nerve endings in the uninjured
      state in Sprague Dawley rats. PERSPECTIVE: This study indicates the alpha1
      adrenergic receptor subtype mediates adrenergic augmentation of the activation of
      sensory nerves by purinergic P2X3 receptors (respond to ATP) in the periphery.
      Observations are potentially relevant to chronic pain conditions in which
      sympathetic nerves influence sensory nerves.

PMID- 17512256
TI  - Phase 1A safety assessment of intravenous amitriptyline.
AB  - The antidepressant amitriptyline is used as an adjuvant in the treatment of
      chronic pain. Among its many actions, amitriptyline blocks Na+ channels and
      nerves in several animal and human models. As perioperative intravenous lidocaine
      has been suggested to decrease postoperative pain, amitriptyline, because of its
      longer half-life time, might be more useful than lidocaine. However, the use of
      intravenous amitriptyline is not approved by the US Food and Drug Administration.
      We therefore investigated the adverse effects of preoperative intravenous
      amitriptyline in a typical phase 1A trial. After obtaining written Food and Drug
      Administration and institutional review board approval, we obtained written
      consent for preoperative infusion of amitriptyline in an open-label, dose
      escalating design (25, 50, and 100 mg, n=5 per group). Plasma levels of
      amitriptyline/nortriptyline were determined, and adverse effects were recorded in
      a predetermined symptom list. Infusion of 25 and 50 mg amitriptyline appears to
      be well tolerated; however, the study was terminated when 1 subject in the 100-mg
      group developed severe bradycardia. Intravenous infusion of amitriptyline (25 to
      50 mg over 1 hour) did not create side effects beyond dry mouth and drowsiness,
      or dizziness, in 2 of our 10 otherwise healthy participants receiving the 25- to
      50-mg dose. An appropriately powered future trial is necessary to determine a
      potential role of amitriptyline in decreasing postoperative pain. PERSPECTIVE:
      Amitriptyline potently blocks the persistently open Na+ channels, which are known
      to be instrumental in various pain states. As this occurs at very low plasma
      concentrations, a single preoperative intravenous infusion of amitriptyline could
      provide long-lasting pain relief and decrease the incidence of chronic pain.

PMID- 17512258
TI  - Adipokinetic hormone-induced enhancement of antioxidant capacity of Pyrrhocoris
      apterus hemolymph in response to oxidative stress.
AB  - The in vivo effects of oxidative stress on adipokinetic hormone (AKH) titer in
      short-winged (brachypterous) males of the firebug Pyrrhocoris apterus were tested
      using paraquat (PQ), a bipyridilium herbicide. PQ undergoes a cyclic redox
      reaction with oxygen during microsomal and electron transfer reactions forming
      free radicals in the insect body. Oxidative insult (40 pmol PQ) resulted in
      enhanced protein carbonylation (a biomarker for oxidative stress) and a depletion
      of glutathione (GSH) pool in the hemolymph. Interestingly, AKH titer was
      significantly enhanced in hemolymph at 4 h post inoculation of PQ, while its
      content in CNS (brain with corpora cardiaca) showed non-specific changes in
      comparable period. Co-injection of AKH with PQ (40 pmol each) reversed these
      effects by decreasing protein carbonyl formation, increasing reduced GSH levels,
      and enhancing the total antioxidant capacity of cell free plasma. Our results
      indicate that there is a positive feedback regulation between an oxidative
      stressor action and the level of AKH in insect body, and that AKHs might be
      involved in the activation of antioxidant protection mechanism.

PMID- 17512259
TI  - caCORE version 3: Implementation of a model driven, service-oriented architecture
      for semantic interoperability.
AB  - One of the requirements for a federated information system is interoperability,
      the ability of one computer system to access and use the resources of another
      system. This feature is particularly important in biomedical research systems,
      which need to coordinate a variety of disparate types of data. In order to meet
      this need, the National Cancer Institute Center for Bioinformatics (NCICB) has
      created the cancer Common Ontologic Representation Environment (caCORE), an
      interoperability infrastructure based on Model Driven Architecture. The caCORE
      infrastructure provides a mechanism to create interoperable biomedical
      information systems. Systems built using the caCORE paradigm address both aspects
      of interoperability: the ability to access data (syntactic interoperability) and
      understand the data once retrieved (semantic interoperability). This
      infrastructure consists of an integrated set of three major components: a
      controlled terminology service (Enterprise Vocabulary Services), a standards
      based metadata repository (the cancer Data Standards Repository) and an
      information system with an Application Programming Interface (API) based on
      Domain Model Driven Architecture. This infrastructure is being leveraged to
      create a Semantic Service-Oriented Architecture (SSOA) for cancer research by the
      National Cancer Institute's cancer Biomedical Informatics Grid (caBIG).

PMID- 17512260
TI  - Medical diagnosis of atherosclerosis from Carotid Artery Doppler Signals using
      principal component analysis (PCA), k-NN based weighting pre-processing and
      Artificial Immune Recognition System (AIRS).
AB  - In this study, we proposed a new medical diagnosis system based on principal
      component analysis (PCA), k-NN based weighting pre-processing, and Artificial
      Immune Recognition System (AIRS) for diagnosis of atherosclerosis from Carotid
      Artery Doppler Signals. The suggested system consists of four stages. First, in
      the feature extraction stage, we have obtained the features related with
      atherosclerosis disease using Fast Fourier Transformation (FFT) modeling and by
      calculating of maximum frequency envelope of sonograms. Second, in the
      dimensionality reduction stage, the 61 features of atherosclerosis disease have
      been reduced to 4 features using PCA. Third, in the pre-processing stage, we have
      weighted these 4 features using different values of k in a new weighting scheme
      based on k-NN based weighting pre-processing. Finally, in the classification
      stage, AIRS classifier has been used to classify subjects as healthy or having
      atherosclerosis. Hundred percent of classification accuracy has been obtained by
      the proposed system using 10-fold cross validation. This success shows that the
      proposed system is a robust and effective system in diagnosis of atherosclerosis
      disease.

PMID- 17512261
TI  - Endothelium protectant and contractile effects of the antivaricose principle
      escin in rat aorta.
AB  - The triterpene saponin escin is the active component of the extract of seeds of
      Aesculus hippocastanum used in the treatment of chronic venous insufficiency.
      Escin is also used experimentally to increase membrane permeability in isolated
      cells. Since endothelial dysfunction is postulated to be involved in venous
      insufficiency, the possible endothelium-protectant effect of escin was explored
      in rat aortic rings, a model widely used to study such effects with
      cardiovascular agents. Escin enhanced endothelium-dependent relaxation induced by
      acetylcholine when such relaxation had been reduced by exposure to the superoxide
      ion generator pyrogallol. This effect was attributed to enhanced nitric oxide
      production by endothelial nitric oxide synthase, a calcium-dependent enzyme,
      activated by the increased endothelial cell permeability to calcium induced by
      escin. Another effect of escin thought to contribute to its therapeutic activity
      is its ability to produce venous contraction. The compound was found to induce
      concentration-related contraction also in rat aortic rings. This response was
      partially inhibited by removal of the endothelium or by preincubation with
      indomethacin, and was completely abolished by incubation in a calcium-free
      perfusion fluid. Contraction was considered to be due mainly to the
      aforementioned effect on calcium permeability, with some mediation by release of
      endothelial vasoconstrictor prostanoids. It was concluded that, in rat aorta,
      escin possesses an endothelium-protectant action and a direct contractile effect.
      The former could contribute to its beneficial effect in the treatment of venous
      insufficiency, while the latter could constitute a limiting side effect.

PMID- 17512262
TI  - Noradrenergic inhibitory modulation in the caudal commissural NTS of the pressor
      response to chemoreflex activation in awake rats.
AB  - In the present study we evaluated the possible modulatory role of noradrenaline
      on the neurotransmission of the peripheral chemoreflex afferents in the caudal
      commissural NTS of awake rats. To reach this goal we performed a dose-response
      curve to microinjection of increasing dose of noradrenaline into the caudal
      commissural NTS of awake rats and then the threshold dose, which produces minor
      changes in the baseline mean arterial pressure, was selected to be used in the
      chemoreflex experiment. The peripheral chemoreflex was activated with KCN before
      and after bilateral microinjections of noradrenaline (5 nMol/50 nL, threshold
      dose) into the NTS. The data show that microinjection of noradrenaline into the
      caudal NTS produced a significant reduction in the pressor response to the
      chemoreflex 30 s after the injection when compared to the control response (30+/
      6 vs. 49+/-3 mm Hg) but no significant changes in the bradycardic response. The
      data indicate that noradrenaline in the caudal commissural NTS of awake rats may
      play an important inhibitory neuromodulatory role on the processing of the
      pressor/sympathoexcitatory component of the chemoreflex.

PMID- 17512263
TI  - Body water balance and body temperature in vasopressin V1b receptor knockout
      mice.
AB  - In an attempt to determine whether there is a specific vasopressin receptor
      (V(1b)) subtype involved in the regulation of body water balance and temperature,
      vasopressin V(1b) receptor knockout mice were used. Daily drinking behavior and
      renal excretory function were examined in V(1b)-deficient (V(1b)(-/-)) and
      control (V(1b)(+/+)) mice under the basal and stress-induced condition. In
      addition, body temperature and locomotor activity were measured with a
      biotelemetry system. The baseline daily water intake and urine volume were larger
      in V(1b)(-/-) mice than in V(1b)(+/+) mice. V(1b)(-/-) mice (V(1b)(-/-)) had
      significantly higher locomotor activity than wild-type, whereas the body
      temperature and oxygen consumption were lower in V(1b)(-/-) than in the
      V(1b)(+/+) mice. Next, the V(1b)(-/-) and V(1b)(+/+) mice were subjected to water
      deprivation for 48 hr. Under this condition, their body temperature decreased
      with the time course, which was significantly larger for V(1b)(-/-) than for
      V(1b)(+/+) mice. Central vasopressin has been reported to elicit drinking
      behavior and antipyretic action, and the V(1b) receptor has been reported to be
      located in the kidney. Thus, the findings suggest that the V(1b) receptor may be,
      at least in part, involved in body water balance and body temperature regulation.

PMID- 17512264
TI  - Sir2 and calorie restriction in yeast: a skeptical perspective.
AB  - Activation of Sir2-family proteins in response to calorie restriction (CR) has
      been proposed as an evolutionarily conserved mechanism for life span extension.
      This idea has been called into question with the discovery that Sir2-family
      proteins are not required for life span extension from CR in yeast. We present
      here a historical perspective and critical evaluation of the model that CR acts
      through Sir2 in yeast, and interpret prior reports in light of more recent
      discoveries. Several specific cases where the Sir2 model of CR is inconsistent
      with experimental data are noted. These shortcomings must be considered along
      with evidence supporting a role for Sir2 in CR in order to fully evaluate the
      validity of this model.

PMID- 17512265
TI  - Formation and adhesion of biomimetic hydroxyapatite deposited on titanium
      substrates.
AB  - This study has been carried out to investigate the bioactivity of rutile and to
      deposit hydroxyapatite (HA) on heat-treated titanium through a biomimetic method.
      Biomimetic deposition of HA has gained large interest because of its low
      deposition temperature and good step coverage; however, it demands a substrate
      with bioactive properties. Commercially pure titanium is not bioactive but it can
      acquire bioactive properties through various surface treatments. In the present
      study, titanium plates were heat-treated at 800 degrees C to achieve rutile
      TiO(2) surfaces. These samples were immersed in a phosphate-buffered saline
      solution for seven days in order to deposit a HA layer on the surface. The rutile
      TiO(2) surfaces were found to be highly bioactive: after seven days of immersion,
      a layer of HA several micrometers thick covered the plates. The HA surfaces were
      confirmed by electron microscopy and X-ray diffraction. A scratch test was used
      to assess the adhesion of the HA coatings. This is a standard method to provide a
      measure of the coating-to-substrate adhesion and was found to be a useful method
      to test the thin HA coatings deposited on the bioactive surfaces. The critical
      pressure of the layer was estimated to be 2.4+/-0.1GPa.

PMID- 17512266
TI  - Retroaortic left renal vein fistula masquerading as pelvic congestion syndrome:
      case report.
AB  - This case study shows how aorto-left renal vein fistula in a female can present
      with left-sided pelvic pain secondary to ovarian vein reflux, a symptom of pelvic
      congestion syndrome, next to typical features such as epigastric and back pain.

PMID- 17512267
TI  - Mini replants: fingertip replant distal to the IP or DIP joint.
AB  - Amputations through the distal interphalangeal joint or distal to this joint are
      frequent and they represent probably one of the best indications for
      replantation. Details on the vascular anatomy of the fingertip have to be
      perfectly known by the surgeon who will have to deal with these replantations.
      Factors such as age, mechanism of amputation and type of anastomosis will
      influence the overall success rate of the procedure. Return of a true static two
      points discrimination can be observed in children even in the absence of any
      neural repair.

PMID- 17512268
TI  - Temporary ectopic implantation of digits prior to reconstruction of a hand
      without metacarpals.
AB  - Temporary ectopic implantation has been described for a variety of injuries, with
      several different implantation sites used. Although varied results have been
      achieved, many feel this technique has a role to play under special
      circumstances. We describe the ectopic implantation of digits to the
      contralateral forearm, with subsequent reconstruction of the injured hand when
      combined with microvascular toe transfer. The outcome was a functionally useful
      hand which could be incorporated into daily life, and a cosmetic appearance
      preferable to that of amputation. We feel ectopic implantation still has a
      valuable role to play in carefully selected cases.

PMID- 17512270
TI  - Giant cell tumour of the flexor tendon sheath of the foot.
AB  - Giant cell tumour of tendon sheath (GCTTS) is a benign, soft-tissue tumour
      arising from synovial cells of tendon sheaths. Because of the high incidence of
      recurrence, radical surgical excision is the treatment of choice. Presented here
      is a rare case of this lesion originating from flexor tendon sheaths of the foot.
      A 40-year-old Russian white female presented to the clinic with a slightly
      painful soft tissue mass in her right foot along the medial aspect of her ankle.
      She gave a one-year history of the mass and was concerned about increasing size,
      pain, and plantar numbness as well as limitation in her movements to some extent.
      Interpretation of the magnetic resonance imaging failed to include giant cell
      tumours in the preoperative differential diagnosis. Considering the proximity of
      the tumour to important anatomic structures, less radical but grossly complete
      excision was employed, followed by appropriate periodic re-evaluation. Pedal
      involvement of GCTTS is rare with a reported predilection for dorsal and lateral
      localisations around the ankle. Our case presents an unusual occurrence of this
      tumour with medial localisation of the lesion in the foot, extending through the
      tarsal tunnel.

PMID- 17512271
TI  - The quest for procedural safety: a suggested framework for the clinical study of
      operator-based technical errors during surgical procedures.

PMID- 17512272
TI  - Esophageal reconstruction after caustic injury: is there still a place for right
      coloplasty?
AB  - BACKGROUND: Through a systematic policy of using the right colon as an esophageal
      substitute, the authors analyze the reliability of this transplant for
      reconstruction after digestive caustic injury. METHODS: From 1995 to 2005, a
      right coloplasty was attempted in 81 patients after total esophagogastrectomy (n
      = 57) or for esophageal stricture (n = 24). RESULTS: The use of the right colon
      was not possible in 10 patients (12%) because of insufficient blood supply. In
      addition, postoperative right colic graft necrosis occurred in 5 patients.
      Cervical fistula occurred in 25 patients (31%). Opening of the thoracic inlet was
      associated with a lower rate of this complication (P = .04). At the end of the
      follow-up, 71 patients (88%) recovered oral feeding. CONCLUSION: Attempt to use
      the right colon as an esophageal substitute failed in 18% of the patients.
      Despite high rates of cervical complications, in part linked to the peculiar
      setting of caustic injury, functional results remains satisfactory.

PMID- 17512273
TI  - Use of preoperative parathyroid fine-needle aspiration and parathormone assay in
      the primary hyperparathyroidism with concomitant thyroid nodules.
AB  - BACKGROUND: Although the sensitivity of imaging studies is high in solitary
      parathyroid adenomas, negative results are inevitable. The aims of this
      prospective clinical study are to evaluate the impact of the presence of thyroid
      disease on the sensitivity and positive predictive value (PPV) of ultrasonography
      (US), sestamibi (MIBI), and parathyroid fine needle aspiration and parathormone
      assay (PTH-FNA). PATIENTS: The patients were divided into 4 groups according to
      preoperative imaging studies: group A (n = 62) with US, group B (n = 62) with
      MIBI, group C (n = 62) with US + MIBI, and group D (n = 62) with PTH-FNA. These 4
      groups were subdivided according to the presence (group 1) or absence (group 2)
      of thyroid nodule. RESULTS: In the overall patients, the sensitivity and PPV of
      PTH-FNA to localize parathyroid adenoma was higher compared with US, MIBI, and US
      + MIBI (100% and 100% versus 96% and 91% versus 92% and 87% versus 95% and 94%,
      respectively, P < .05). The sensitivity and PPV of US, MIBI, and US + MIBI in the
      patients without thyroid nodule was higher compared with the patients with
      thyroid nodule (100% and 100%, 100% and 96%, 100% and 100% versus 93% and 84%,
      85% and 80%, 96% and 86%, respectively, P < .05). The sensitivity and PPV of the
      PTH-FNA was 100% in the patients with and without a thyroid nodule. CONCLUSION:
      PTH-FNA can be performed safely for the confirmation of parathyroid adenoma
      localized by preoperative imaging studies. In patients with a concomitant thyroid
      nodule, PTH-FNA was more accurate to detect the parathyroid adenoma than the
      other imaging studies.

PMID- 17512274
TI  - Peritoneal cytology in colorectal cancer: incidence and prognostic value.
AB  - BACKGROUND: The value of peritoneal washing cytology on prognosis is not clear
      yet. The aims of our prospective study were to consider the incidence and
      prognostic value of peritoneal cytology. METHODS: From 1996 to 2003, washing
      cytology was performed in 88 patients who underwent surgery for colorectal
      cancer. Before exploration and manipulation of the tumor, each of the peritoneal
      cavities next to the tumor site, subhepatic and rectovesical recesses, were
      irrigated with 50 mL saline, and then the aspirates were taken for cytological
      evaluation. RESULTS: Thirteen (14.7%) of 88 patients had positive cytology.
      Although necrosis, depth of invasion, differentiation of the tumor, macroscopic
      peritoneal dissemination, and ascites were correlated with positive cytology;
      multivariate analyses revealed the depth of invasion, presence of necrosis, and
      differentiation of the tumor as the factors affecting the cytology. The disease
      free and overall-survival times in patients with positive and negative peritoneal
      washing cytology were 56.36, 61.40 and 52.08, 63.94 months, respectively (P >
      .05). CONCLUSION: The presence of free malignant cells in the peritoneal cavities
      of patients who underwent curative resection for colorectal cancer provides no
      further prognostic value over the current staging systems.

PMID- 17512275
TI  - Interleukin-18 restores immune suppression in patients with nonseptic surgery,
      but not with sepsis.
AB  - BACKGROUND: We investigated cellular immune responses, in particular interferon
      gamma (IFN-gamma) production, by peripheral blood mononuclear cells (PBMCs) in
      patients with septic and nonseptic surgical stress, focusing on interleukin (IL)
      18 and its receptor (IL-18R). METHODS: Thirty-two patients with alimentary tract
      carcinoma who underwent elective surgery (OP) and 26 septic patients (SP) with
      peritonitis were enrolled in this study. Blood was collected on the first
      postoperative day (POD1), POD5, POD10, and POD15 in the OP group and on the
      emergency admission in the SP group. Ten healthy volunteers served as controls.
      PBMCs were cultured in the presence of anti-CD3 antibody or IL-2 and IL-12, with
      or without additional IL-18 stimulation, to measure IFN-gamma production. IL-18R
      expression on CD56+ NK (natural killer) cells was evaluated by flow cytometry.
      RESULTS: IL-2- and IL-12-induced IFN-gamma production by PBMCs was suppressed
      significantly in both the OP (POD5) and SP groups compared with that in healthy
      controls. Interestingly, additional IL-18 stimulation up-regulated IFN-gamma
      production by PBMCs in the OP group as well as the control group, but not in the
      SP group. IL-18R expression on CD56+ NK cells was maintained consistently in the
      OP group as well as the control group, but decreased in the SP group.
      CONCLUSIONS: IFN-gamma production induced by cytokines (IL-2 and IL-12) was
      suppressed in PBMCs from both patients with sepsis and those who had undergone
      elective surgery. However, IL-18R expression on CD56+ NK cells was different
      between patients with sepsis and nonseptic surgical stress. Our results suggest
      that exogenous IL-18 administration may be effective in preventing immune
      suppression in patients with nonseptic elective surgery.

PMID- 17512276
TI  - Comorbidity is a major determinant of severity in acute diverticulitis.
AB  - BACKGROUND: Acute colonic diverticulitis may be simple or very complicated. Not
      much is understood about what factors determine severity. Answering this question
      may have therapeutic implications. METHODS: A retrospective review was performed
      consisting of teaching hospital admissions for simple or complicated acute
      diverticulitis. The intent was to identify characteristics of and differences
      between the 2 groups. The Charlson index was used to assess states of preexisting
      health (comorbidity). RESULTS: In multivariate analysis, the presence of a major
      degree of comorbidity (Charlson score 3 or greater) was strongly associated with
      complicated disease (P = 0.02) as was the use of nonsteroidal anti-inflammatory
      drugs (P = .01). Deaths were not seen below age 50, and high Charlson score also
      strongly predicted mortality (P < .0001). CONCLUSIONS: There are significant
      differences between patients presenting with simple and complicated
      diverticulitis, and the amount of associated comorbidity (as measured by Charlson
      score) appears to be a major one. Because of the high mortality seen in patients
      with Charlson scores 3 or greater and complicated diverticulitis, we believe that
      an early surgical approach should be considered for them, particularly if they
      are 50 or older.

PMID- 17512277
TI  - Comparison of two models for the prediction of nonsentinel node metastases in
      breast cancer.
AB  - BACKGROUND: It is debated whether all patients with a positive sentinel node
      dissection (SLND) should be submitted to axillary lymph node dissection (ALND).
      Models have been developed to estimate the likelihood of nonsentinel node (non
      SLN) metastases. METHODS: The accuracy of the Memorial Sloan-Kettering Cancer
      Center (MSKCC) nomogram and MD Anderson scoring system for the prediction of non
      SLN status was tested in a consecutive series of 186 SLN-positive breast cancer
      patients. A multivariate analysis was performed to assess which parameters
      independently predicted the presence of non-SLN metastases. RESULTS: The
      predictive accuracy of the MSKCC nomogram measured by the receiver operating
      characteristic curve was 0.71, and it was best in patients with <10% risk of non
      SLN metastases (sensitivity 100% and specificity 96%). The MD Anderson score
      predicted non-SLN involvement with low accuracy because it classified 85% of the
      patients in the intermediate-risk groups. Only SLN macrometastases and tumor
      multifocality independently predicted non-SLNs involvement. CONCLUSIONS: The
      MSKCC nomogram can help individualize the surgical treatment of SLN-positive
      breast cancer when the likelihood of further axillary involvement is low or
      surgical risks are higher.

PMID- 17512278
TI  - The use of a harmonic scalpel in thyroid surgery: report of a 3-year experience.
AB  - BACKGROUND: Hemostasis in thyroid surgery is of utmost importance for a
      successful surgery and an uneventful postoperative course. The present article
      reports a single surgeon's 3-year experience in the use of the harmonic scalpel.
      The device was developed in the early 1990s and offered adequate and safe
      hemostasis for vessels up to 3 mm in width. METHODS: This was a prospective
      observational study. Data sheets from all patients who had surgery by a single
      endocrine surgeon in the period from 1999 to 2004 were evaluated. Patients were
      divided into 3 groups based on the surgical technique used: group I comprised the
      conventional knot-and-tie technique, group II comprised the ligation of all but
      the superior thyroid vessels with a scalpel, and group III comprised patients in
      whom the device was used exclusively. The groups were compared in regard to
      surgical time, cost, and complication rate. RESULTS: A total of 272 patients were
      included in the study: 107 patients were included in group I, 77 in group II, and
      88 group III. The surgical time of group I differed significantly compared with
      groups II and III (P < .0001 in both cases). Surgical times between groups II and
      III did not differ significantly (P = .701). CONCLUSIONS: The use of the harmonic
      scalpel reduces surgical time, but it increases the cost of the surgery. It is
      our belief that by including in the absolute cost the time saved and the
      reduction in human resources needed, the use of the scalpel would prove to be
      economic.

PMID- 17512279
TI  - Improved outcomes with the Prolene Hernia System mesh compared with the time
      honored Lichtenstein onlay mesh repair for inguinal hernia repair.
AB  - BACKGROUND: Inguinal hernia repairs are commonly performed operations. Recently,
      Neumayer et al examined the gold standard Lichtenstein onlay mesh repair (LMR)
      against laparoscopic inguinal hernia repair and showed that the recurrence rates
      are higher for laparoscopic mesh repairs when compared with the open onlay mesh
      repair (laparoscopic = 10.1% versus open = 4.9%). In 1998, the Prolene Hernia
      System (PHS) mesh, consisting of an onlay and an underlay patch attached with a
      connector, was introduced as an option for tension-free open repair of inguinal
      hernias combining the benefits of a posterior and anterior repair from an open
      approach. Our objective was to evaluate the PHS mesh repair versus the LMR for
      inguinal hernias. We hypothesized that the recurrence rate of PHS mesh would be
      lower compared with the LMR with overall similar complication rates. METHODS: PHS
      mesh hernia repairs performed from January 2003 to July 2005 and LMR repairs from
      January 2000 to July 2002 were included. Demographic data such as age, race, and
      gender as well as comorbid conditions such as chronic obstructive pulmonary
      disease, congestive heart failure, previous myocardial infarction, diabetes,
      hypertension, prostatism, and chronic cough were collected. Complications such as
      cord injury, seroma, hematoma, urinary retention, urinary tract infection,
      orchitis, and wound infection were recorded. Recurrences in each group were also
      recorded. A student t test and chi-square analysis were used for statistical
      analysis. RESULTS: Six hundred twenty-two charts were reviewed during the 2 time
      periods (PHS mesh = 321, LMR = 302). The median follow-up for the study was 17
      months. There was no significant difference with regards to age, race, gender, or
      comorbidities between the 2 groups. Overall, there was a trend toward decreased
      complications in the PHS mesh group compared with the LMR group (PHS mesh = 17%,
      LMR = 23%, P = .07), with a significant difference in the hematoma/seroma rates
      (PHS mesh = 6.9%, LMR = 12.6%, P = .015). Finally, there was a significant
      decrease in the recurrence rate for the PHS mesh group when compared with the LMR
      group (PHS mesh = 0.6%, LMR = 2.7%, P = .04). CONCLUSION: Our study shows, during
      a median follow-up of 17 months, improved outcomes by using the PHS mesh compared
      with the gold standard Lichtenstein onlay mesh for inguinal hernias with
      significantly lower recurrence rates. Additionally, in the PHS mesh group, there
      was a trend toward decreased overall complication rates with significantly less
      seroma/hematoma rates. Therefore, the PHS mesh repair may represent a superior
      alternative for the repair of inguinal hernias.

PMID- 17512280
TI  - High-resolution computed tomography accurately predicts resectability in hilar
      cholangiocarcinoma.
AB  - INTRODUCTION: Despite the use of radiologic, endoscopic, and laparoscopic staging
      techniques, the rate of nontherapeutic laparotomies in patients with hilar
      cholangiocarcinoma remains high. This study evaluated the accuracy of
      preoperative high-resolution computed tomography (HRCT) to determine
      resectability in this setting. PATIENTS AND METHODS: Preoperative helical HRCT (2
      contrast phases, rapid intravenous contrast bolus, 2.5-mm section thickness) for
      32 consecutive patients who underwent laparotomy for the diagnosis of hilar
      cholangiocarcinoma from 2000 to 2005 were reviewed by a hepatobiliary
      radiologist. The accuracy of HRCT was determined by comparison of the imaging
      interpretation to intraoperative and pathologic findings. The chi-square test was
      used to identify imaging findings that best predicted unresectability. RESULTS:
      Fourteen of the 32 (44%) study patients were unresectable (extension along bile
      duct, 4; peritoneal metastases, 4; vascular encasement, 3; noncontiguous liver
      metastases, 2; N2 lymphadenopathy, 1). HRCT correctly predicted resectability in
      17 of 18 patients who underwent therapeutic laparotomy (sensitivity = 94%). HRCT
      correctly predicted the inability to resect in 11 of the remaining 14 cases
      (specificity = 79%). In the 3 cases in which HRCT predicted resectability and the
      patient was unresectable, subcentimeter peritoneal disease, a subcentimeter liver
      metastasis, and distal bile duct involvement were responsible factors. The
      negative and positive predictive values of HRCT were 92% and 85%, respectively.
      Individual radiographic findings that best predicted unresectability were
      peritoneal spread (P = .015) and hepatic artery (P = .006) or portal vein (P =
      .002) involvement. CONCLUSIONS: Preoperative HRCT accurately predicts
      resectability in patients with hilar cholangiocarcinoma. Identification of
      specific radiographic features, in particular major vascular involvement and
      peritoneal abnormalities, is now used by our group to avoid unnecessary
      laparotomy.

PMID- 17512281
TI  - Hyalinizing trabecular adenoma--an uncommon thyroid tumor frequently misdiagnosed
      as papillary or medullary thyroid carcinoma.
AB  - BACKGROUND: Hyalinizing trabecular adenoma (HTA) is an uncommon benign thyroid
      tumor that can present as a solitary thyroid nodule, a prominent nodule in a
      multinodular goiter, or as an incidental finding in a thyroidectomy specimen. The
      clinical significance of the lesion is that it is frequently misdiagnosed as
      papillary carcinoma on fine-needle aspiration cytology or as papillary or
      medullary carcinoma on histopathological section. We reviewed our recent
      experience with 7 patients diagnosed with HTA. METHODS: Fine-needle aspiration
      biopsy was performed in 7 patients presenting with a solitary thyroid nodule (n =
      4) or a multinodular goiter (n = 3). The patients underwent total thyroidectomy
      (n = 6) or hemithyroidectomy (n = 1). RESULTS: In 4 patients, the preoperative
      cytology was suggestive of papillary carcinoma, in 2 patients suspicious, and in
      1 patient positive for papillary carcinoma. On histopathological section, 2
      patients had a microscopic HTA, 2 patients had HTA in 1 or 2 nodules of a
      multinodular goiter, and 3 patients had HTA in a solitary nodule. Except in 1
      patient, who had a microscopic focus (3.2 mm) of papillary carcinoma, there was
      no evidence of malignancy in the surgical specimens on permanent
      histopathological section. CONCLUSIONS: Although HTA is a rare condition of the
      thyroid, the surgeon needs to be aware of this entity to be able to better
      discuss the pathological findings with the patient, particularly since some
      pathologists and endocrinologists believe that HTA may represent a malignant
      neoplasm of low metastatic potential.

PMID- 17512282
TI  - Concomitant intraoperative splenic artery embolization and laparoscopic
      splenectomy versus laparoscopic splenectomy: comparison of treatment outcome.
AB  - INTRODUCTION: Although laparoscopic splenectomy has become the preferred
      treatment of choice for hematologic-related splenic disorders, intraoperative
      blood loss remains a common occurrence. In an effort to reduce this risk, we
      evaluate the potential role and clinical outcome of concomitant intraoperative
      splenic artery embolization and laparoscopic splenectomy. METHODS: Between June
      2000 and July 2005, 18 patients with hematologically related splenic disorders
      underwent combined intraoperative splenic artery embolization and laparoscopic
      splenectomy (group 1). For comparison, we studied 18 age- and gender-matched case
      controls undergoing same operations during the same period (group 2).
      Intraoperative data and clinical outcome were compared between the 2 groups.
      RESULTS: Technical success was 100% in group 1. One patient in group 2 was
      converted to open splenectomy because of severe blood loss, resulting in a
      technical success rate of 95%. The mean splenic size in group 1 and group 2 was
      15.5 +/- 4.7 cm (range, 12-23 cm) and 15.7 +/- 6.8 (range, 11-24 cm),
      respectively (not significant [NS]). Mean operative time in group 1 and group 2
      was 175 minutes and 162 minutes, respectively (NS). Significantly less
      intraoperative blood loss was noted in group 1 (mean, 25 mL; range, 15-63 mL)
      compared with group 2 (mean, 240 mL; range, 150-420 mL; P < .003). There was an
      even greater difference in blood loss between the 2 groups when the splenic size
      was greater than 18 cm (mean 35 mL in group 1 versus 350 mL in group 2, P <
      .001). No differences were noted in postoperative recovery, return of bowel
      function, or length of hospital stay between the 2 groups. CONCLUSIONS:
      Concomitant splenic artery embolization and laparoscopic splenic reduced
      operative blood loss when compared with laparoscopic splenectomy procedure alone.
      Splenic artery embolization is a useful intraoperative adjunctive procedure that
      should be considered in patients undergoing laparoscopic splenectomy for
      hematologic disorders who are Jehovah's Witness or with significant hypersplenism
      because of benefit of reduced blood loss.

PMID- 17512283
TI  - A nationwide speed limit < or = 65 miles per hour will save thousands of lives.
AB  - BACKGROUND: The objective of this study was to measure the impact of higher speed
      limits on traffic deaths several years after the repeal of the 55 miles per hour
      (mph) National Maximum Speed Limit (NMSL). METHODS: Traffic fatality rates for
      2003 were calculated for all 50 states and the District of Columbia, and compared
      between states with speed limits < or = 65 mph versus greater than 65 mph,
      adjusted for state differences in vehicle miles traveled and other potential
      confounding factors using negative binomial regression. RESULTS: In 29 states
      with speed limits greater than 65 mph, there was a 13% increase in the risk of
      traffic fatalities (risk ratio 1.13, 95% confidence interval [CI] 1.03 to 1.24, P
      = .009). An estimated 2,985 lives may be saved per year with a nationwide speed
      limit of 65 mph or less. CONCLUSIONS: Nationwide restriction of speed limits to
      65 mph or less will save almost 3,000 lives every year.

PMID- 17512284
TI  - Effects of a membrane-permeable radical scavenger, Tempol, on healing of colonic
      anastomoses in the cecal ligation and puncture model of polymicrobial sepsis in
      rats.
AB  - BACKGROUND: Tempol (Sigma-Aldrich, Steinheim, Germany) is a stable piperidine
      nitroxide of low molecular weight that permeates biologic membranes and scavenges
      superoxide anions in vitro. In recent animal studies, the delaying effect of
      intraperitoneal sepsis on the healing of colonic anastomoses has been shown. In
      this study we aimed to investigate the effects of Tempol on the healing of
      colonic anastomoses in the presence of polymicrobial sepsis. METHODS: Anastomosis
      of the left colon was performed on the day after cecal ligation and puncture
      (CLP) in 30 rats that were divided into 3 groups: sham-operated control
      (laparotomy and cecal mobilization, group I, n = 10), CLP (group II, n = 10),
      Tempol-treated group (30 mg/kg intravenously before the construction of colonic
      anastomosis, group III, n = 10). On postoperative day 6, all animals were killed
      and anastomotic bursting pressures were measured in vivo. Tissue samples were
      obtained for further investigation of anastomotic hydroxyproline (HP) contents,
      perianastomotic myeloperoxidase (MPO) activity, malondialdehyde (MDA), and
      glutathione (GSH) levels. RESULTS: There was a statistically significant increase
      in MPO activity and MDA levels in the CLP group (group II), along with a decrease
      in GSH levels, anastomotic HP contents, and bursting pressure values when
      compared with controls (group I). However, Tempol treatment led to a
      statistically significant increase in anastomotic bursting pressure values,
      tissue HP contents, and GSH levels, along with a decrease in MPO activity and MDA
      levels in group III (P < .05). CONCLUSIONS: This study showed that Tempol
      treatment significantly prevented the delaying effect of CLP-induced
      polymicrobial sepsis on anastomotic healing in the left colon. Further clinical
      studies are needed to clarify whether Tempol may be a useful therapeutic agent to
      increase the safety of the anastomosis during particular surgeries in which
      sepsis-induced organ injury occurs.

PMID- 17512285
TI  - Lipopolysaccharide activation of pericyte's Toll-like receptor-4 regulates co
      culture permeability.
AB  - BACKGROUND: Pericytes (PCs) have a synergistic relationship with endothelial
      cells (MVEC) in regulating capillary permeability. PCs express Toll-like receptor
      4 (TLR-4). We hypothesize one mechanism of MVEC/PC co-culture permeability is
      regulated through lipopolysaccharide (LPS) activation of pericyte TLR-4. METHODS:
      Rat PCs were harvested and cultured. PCs were transfected with siRNA targeted to
      TLR-4. Western blotting was used to confirm gene silencing of TLR-4. A previously
      described co-culture permeability assay was performed after LPS treatment.
      RESULTS: Western blot confirmed successful silencing of TLR-4 in PCs, which was
      sustained for 7 days. A dose- and time-dependent effect of LPS on albumin
      clearance was seen in MVEC/PC co-cultures. Co-cultures with TLR-4 silenced in PCs
      eliminated the LPS dose-dependent increase in albumin clearance. CONCLUSIONS: TLR
      4 regulates pericyte mediated capillary leak seen with LPS exposure. Our TLR-4
      silencing model can be used to further investigate TLR-4's role in pericyte
      mediated capillary leak.

PMID- 17512286
TI  - Giant retroperitoneal teratoma in an adult.

PMID- 17512287
TI  - Restricted cystic duct carcinoma.

PMID- 17512288
TI  - Cavernous transverse mesocolonic lymphangioma in an adult.

PMID- 17512289
TI  - Riolan's arch: confusing, misnomer, and obsolete. A literature survey of the
      connection(s) between the superior and inferior mesenteric arteries.
AB  - BACKGROUND: There are 2 interpretations of Riolan's arch: (1) Riolan's arch is
      identical to a central part of the marginal artery (MA), connecting the superior
      (SMA) and the inferior mesenteric (IMA) arteries; and (2) Riolan's arch
      represents a rare artery, connecting the SMA and the IMA. The current review aims
      to emphasize the clinical importance of the colon's vasculature and to show the
      feasibility of abolishing the terms "Riolan's arch" and "meandering mesenteric
      artery." METHODS: A literature survey was performed. RESULTS: It appears that no
      distinct identity can be ascribed to Riolan's arch and that the "meandering
      mesenteric artery" represents an angiographically hypertrophied MA and/or the
      ascending branch of the left colic artery. However, a rare, centrally located,
      communicating artery has been described. Generally, the MA is sufficient for left
      colic circulation after ligation of the IMA, but at the splenic flexure, patency
      of the ascending branch of the left colic artery can be primordial. CONCLUSION:
      As connections between the SMA and the IMA can be adequately described using
      structures mentioned in Terminologica Anatomica, the terms "Riolan's arch" and
      "meandering mesenteric artery" should be abolished.

PMID- 17512290
TI  - Pancreatic cysts: a proposed management algorithm based on current evidence.
AB  - BACKGROUND: Currently, the management strategy of pancreatic cyst (PC) remains
      controversial because of the inability to diagnose this type of cyst accurately
      and the limited knowledge of its natural history. Previously, many clinicians
      have advocated an aggressive resectional policy. This approach is no longer
      appropriate, and the number of PCs detected incidentally has increased. This
      study reviews the present literature and attempts to provide a management
      algorithm of pancreatic cysts based on currently available evidence. METHODS: A
      Medline search was conducted to identify studies investigating PC, with
      particular emphasis placed on studies addressing its diagnosis and management.
      Additional articles were obtained from the reference lists of key articles and
      recent reviews. COMMENTS: Based on current evidence, the optimal management of PC
      remains an art and should be individualized based on the risk-benefit ratio of
      surgery, which is influenced by multiple factors, such as the patient's potential
      life expectancy, surgical risk; and malignant potential of the cyst. Our proposed
      management algorithm is based on an individual's predicted risk-benefit ratio of
      surgery. Prospective evaluation of the algorithm is needed to determine its
      integrity.

PMID- 17512291
TI  - Do medical students respond empathetically to a virtual patient?
AB  - BACKGROUND: Significant information exchange occurs between a doctor and patient
      through nonverbal communication such as gestures, body position, and eye gaze. In
      addition, empathy is an important trust-building element in a physician: patient
      relationship. Previous work validates the use of virtual patients (VP) to teach
      and assess content items related to history-taking and basic communication
      skills. The purpose of this study was to determine whether more complex
      communication skills, such as nonverbal behaviors and empathy, were similar when
      students interacted with a VP or standardized patient (SP). METHODS: Medical
      students (n = 84) at the University of Florida (UF) and the Medical College of
      Georgia (MCG) underwent a videotaped interview with either a SP or a highly
      interactive VP with abdominal pain. In the scenario, a life-sized VP was
      projected on the wall of an exam room in SP teaching and testing centers at both
      institutions. VP and SP scripted responses to student questions were identical.
      To prompt an empathetic response (ie, acknowledging the patients' feelings),
      during the interview the VP or SP stated "I am scared; can you help me?"
      Clinicians (n = 4) rated student videotapes with respect to nonverbal
      communication skills and empathetic behaviors using a Likert-type scale with
      anchored descriptors. RESULTS: Clinicians rated students interacting with SPs
      higher with respect to the nonverbal communication skills such as head nod (2.78
      +/- .79 vs 1.94 +/- .44, P < .05), and body lean (2.97 +/- .94 vs 1.93 +/- .58, P
      < .05), level of immersion in the scenario (3.31 +/- .49 vs 2.26 +/- .52, P <
      .05), anxiety (1.16 +/- .31 vs 1.45 +/- .33, P < .05), attitude toward the
      patient (3.24 +/- .43 vs 2.89 +/- .36, P < .05), and asking clearer questions
      (3.06 +/- .32 vs 2.51 +/- .32, P < .05) compared to the VP group. The students in
      the SP group also had a higher empathy rating (2.75 +/- .86 vs 2.16 +/- .83, P <
      .05) and better overall rating (4.29 +/- 1.32 vs 3.24 +/- 1.06, P < .05) than the
      VP group. Empathy was positively correlated with the observed nonverbal
      communication behaviors. Eye contact was the most strongly correlated with
      empathy (r = .57, P < .001), followed by head nod (r = .55, P < .001) and body
      lean (r = .49, P < .001). CONCLUSIONS: Medical students demonstrate nonverbal
      communication behaviors and respond empathetically to a VP, although the quantity
      and quality of these behaviors were less than those exhibited in a similar SP
      scenario. Student empathy in response to the VP was less genuine and not as
      sincere as compared to the SP scenario. While we will never duplicate a real
      physician/patient interaction, virtual clinical scenarios could augment existing
      SP programs by providing a controllable, secure, and safe learning environment
      with the opportunity for repetitive practice.

PMID- 17512292
TI  - Evaluating resident candidates: does closed file review impact faculty ratings?
AB  - BACKGROUND: The purpose of this study was to examine faculty ratings of resident
      candidates in closed and open file conditions. METHODS: Surgical faculty
      conducted interviews of 70 resident candidates. Interviewers completed an
      evaluation following a closed file interview then reviewed the candidate's
      Electronic Residency Application Service file and completed the evaluation again.
      RESULTS: A multivariate analysis of variance (MANOVA) yielded significant file x
      familiarity (P < .01), familiarity x attribute (P < .01), and file x familiarity
      x attribute (P < .05) interactions. Analyses for each attribute revealed
      consistent findings in ratings of candidates' intelligence, maturity,
      interpersonal skills, motivation for learning, ability to work with others,
      qualifications to succeed in surgery, and likelihood to succeed in surgery. Known
      candidates were rated higher until files were examined. After file review,
      unknown candidates were seen to be as strong as or stronger than known
      candidates. CONCLUSION: Interviewers rate known and unknown candidates
      differently in open and closed file conditions.

PMID- 17512293
TI  - Fear of missing a lesion: use of simulated breast models to decrease student
      anxiety when learning clinical breast examinations.
AB  - BACKGROUND: Medical students experience a considerable amount of discomfort
      during their training. The purpose of the current study was to identify sources
      of student anxiety when learning clinical breast examinations (CBEs) and to
      evaluate the effects of simulated breast models on student comfort. METHODS:
      Simulated breast models were introduced into the curriculum for 175 second-year
      medical students. Using surveys, students identified sources of anxiety and rated
      their comfort levels when learning CBE skills. RESULTS: "Fear of missing a
      lesion" and the "Intimate/personal nature of the exam" accounted for 73.8% of
      student anxiety when learning CBEs. In addition, there were significant
      improvements (P < .05) in student comfort levels when using simulated breast
      models to learn CBE skills. CONCLUSIONS: We have identified 2 of the top causes
      of anxiety for second-year medical students learning CBE. In addition, we found
      simulated breast models to be effective in increasing student comfort levels when
      learning CBEs.

PMID- 17512294
TI  - A CRASH course in procedural skills improves medical students' self-assessment of
      proficiency, confidence, and anxiety.
AB  - BACKGROUND: Medical students enter the clinical education years with minimal
      exposure to procedural skills. This study aims to determine the effect of a pre
      clinical skills course on students' ratings of proficiency, confidence, and
      anxiety levels. METHODS: An elective pre-clinical course in procedural skills was
      given to medical students prior to clinical rotations. Self-assessment of
      proficiency, confidence, and anxiety in performing these skills was made prior to
      and on completion of the course. RESULTS: Course participants reported low
      proficiency and confidence, and high anxiety regarding performing procedural
      skills. Following the course, there was significant improvement in self-assessed
      proficiency, confidence, and anxiety. There were no gender differences in
      responses. CONCLUSIONS: Medical students entering clinical rotations have poor
      self-assessment of proficiency, low confidence, and high anxiety regarding
      procedural skills. A concentrated course in procedural skills significantly
      improved students' assessment of their proficiency, confidence, and anxiety
      levels.

PMID- 17512295
TI  - Curriculum-based solo virtual reality training for laparoscopic intracorporeal
      knot tying: objective assessment of the transfer of skill from virtual reality to
      reality.
AB  - BACKGROUND: Very few studies have addressed the transferability of skills from
      virtual reality (VR) to real life. The aim of this study was to assess the
      feasibility and effectiveness of teaching intracorporeal knot tying (ICKT) by VR
      simulation only. METHODS: Twenty novices underwent structured training of basic
      skills training on the Minimally Invasive Surgical Trainer simulator (Mentice AB,
      Gothenburg, Sweden) followed by knot tying training on the LapSim simulator
      (Surgical Science, Gothenburg, Sweden). They were assessed pre- and post-training
      on a video trainer. Assessment of performance included motion tracking and video
      based checklist. Nonparametric statistical analysis was used, and P < .05 was
      deemed significant. RESULTS: All participants completed a correct knot as
      compared with only 25% before VR training. Time to completion was 66% faster and
      knot quality 45% better after VR training. Significant reduction in number of
      movements (P = .006) and distance traveled (P < .000) by both hands after VR
      training. CONCLUSIONS: Teaching ICKT by VR simulators only is feasible and
      effective. Furthermore, this study highlights the complementary use of different
      VR simulators within a structured curriculum.

PMID- 17512296
TI  - The resident-student teaching encounter: a structured method.

PMID- 17512297
TI  - En bloc stapled diaphragmatic resection for local invasion during hepatectomy: a
      simple technique without opening the pleural cavity.
AB  - Diaphragmatic invasion is not uncommon in patients undergoing hepatectomy for
      liver tumors. Where there are limited attachments of the diaphragm to the tumor,
      the authors describe a stapled technique for en bloc resection of the diaphragm
      without opening the chest cavity, thus performing an oncologic resection, while
      avoiding the need for pleural drainage.

PMID- 17512298
TI  - Immediate reconstruction using inframammary adipofascial flap of the anterior
      rectus sheath after partial mastectomy.
AB  - Treatment of early breast cancer using breast conservative therapy (BCT) usually
      ensures local control and acceptable cosmetic results. To repair defects caused
      by partial mastectomy in the lower region of the breast, some reconstruction
      should be used. We developed a procedure involving the cranial based adipofascial
      (anterior rectus sheath) flap from immediately below the inframammary area for
      the reconstruction of defect due to partial mastectomy for patients with early
      breast cancer. In this procedure, a skin incision is made at the inframammary
      line, and the inframammary skin area is undermined. A tongue shaped flap composed
      of the subcutaneous fat and the anterior sheath of rectus abdominis muscle is
      pulled up and a C-shaped flap is rotated, gathered, and inserted to reconstruct
      the breast defect.

PMID- 17512299
TI  - Esophageal bypass using a gastric tube and a cardiostomy for malignant
      esophagorespiratory fistula.
AB  - Esophageal bypass with a gastric tube and a cardiostomy is a method recently
      devised for malignant esophagorespiratory fistula. This method separates
      completely the alimentary and respiratory tracts. Four patients underwent these
      procedures. No operative deaths occurred, nor was there any anastomotic leakage
      or disruption of the excluded esophagus. The average survival time was 7 months.
      However, all patients were allowed to consume food orally up to the last moment
      of life. This bypass procedure is simple and safe to perform, and is thus a
      feasible treatment choice for patients with such fistulas.

PMID- 17512300
TI  - A novel material in seton treatment of fistula-in-ano.
AB  - Fistula-in-ano is a common surgical problem. Various materials have been used to
      perform the seton technique in the treatment of fistula-in-ano. In this study, a
      novel material, a self-locking cable tie, was used regardless of the fistula
      type. Seventeen consecutive patients with anal fistula underwent surgery with the
      cutting seton technique using the novel material. Nine patients had high
      fistulas. The average tightening was 3.18, the mean fall-out time was 17.41 days,
      and the mean follow-up period was 8.2 months. No recurrences or incontinence were
      recorded. There are statistically significant differences between superficial and
      high fistula cases regarding the number of setons tightening, seton fall-out
      time, and complete healing time. The novel material presented here has some
      advantages: it is cheap, easily available, and easily applied, moreover, a
      gradual tightening can be performed. We think this novel material is a good
      choice in the treatment of fistula-in-ano.

PMID- 17512301
TI  - Proficiency-based virtual reality training significantly reduces the error rate
      for residents during their first 10 laparoscopic cholecystectomies.
AB  - BACKGROUND: Virtual reality (VR) training has been shown previously to improve
      intraoperative performance during part of a laparoscopic cholecystectomy. The aim
      of this study was to assess the effect of proficiency-based VR training on the
      outcome of the first 10 entire cholecystectomies performed by novices. METHODS:
      Thirteen laparoscopically inexperienced residents were randomized to either (1)
      VR training until a predefined expert level of performance was reached, or (2)
      the control group. Videotapes of each resident's first 10 procedures were
      reviewed independently in a blinded fashion and scored for predefined errors.
      RESULTS: The VR-trained group consistently made significantly fewer errors (P =
      .0037). On the other hand, residents in the control group made, on average, 3
      times as many errors and used 58% longer surgical time. CONCLUSIONS: The results
      of this study show that training on the VR simulator to a level of proficiency
      significantly improves intraoperative performance during a resident's first 10
      laparoscopic cholecystectomies.

PMID- 17512303
TI  - The association of fatty acid-binding protein 2 A54T polymorphism with
      postprandial lipemia depends on promoter variability.
AB  - Studies on the association of fatty acid-binding protein 2 (FABP2) A54T and
      promoter polymorphism, and type 2 diabetes mellitus, insulin, and triglyceride
      levels are controversial. The aim of this study was to investigate the
      interfering effect of FABP2 A54T and promoter polymorphism on the postprandial
      response to a mixed meal and an oral glucose load. Seven hundred men from the
      Metabolic Intervention Cohort Kiel underwent a standard glucose tolerance test
      and a standardized mixed meal test and were genotyped by use of the Taqman
      method. When calculated independently from promoter variability, postprandial
      triglyceride levels were significantly higher and postprandial insulin
      sensitivity (homeostasis model assessment index) was lower in homozygous carriers
      of FABP2 T54T compared with carriers of the FABP2 exon wild-type allele (FABP2
      A54A and A54T). This confirms previous findings. The effect of the exon T54T
      genotype on triglyceride levels and insulin sensitivity, however, was dependent
      on promoter variability. We found a significant increase in postprandial
      triglyceride levels and a decrease in insulin sensitivity due to T54T only in the
      presence of the homozygous B genotype at the promoter polymorphism. Similar
      results were obtained after oral glucose tolerance test. Reporter gene assays
      indicated a higher responsiveness to peroxisome proliferator-activating receptor
      gamma (PPAR-gamma)/retinoid X receptor (RXR) of FABP2 promoter B vs promoter A.
      Synergism between a higher inducibility of FABP2 expression and a higher activity
      of T54 variant may explain higher postprandial triglycerides in case of combined
      genotype (promoter B + T54). This interference and different linkage
      disequilibrium between FABP2 exon and promoter polymorphisms may explain the
      different results obtained in different cohorts.

PMID- 17512304
TI  - Attenuation of type 2 diabetes mellitus in the male Zucker diabetic fatty rat:
      the effects of stress and non-volitional exercise.
AB  - To date, a limited number of studies have investigated the effects of exercise on
      the maintenance of endocrine pancreatic adaptations to worsening insulin
      resistance. In particular, the roles of stress hormones that are associated with
      commonly used forced-exercise paradigms are not fully explained. To examine the
      effects of exercise per se in ameliorating pancreatic decompensation over time,
      we investigated the role of forced swimming and sham exercise stress on the
      development of type 2 diabetes mellitus in the Zucker diabetic fatty (ZDF) rat.
      Thirty-two male ZDF rats were obtained at 5 weeks of age and all went through a 1
      week acclimatization period. They were then divided into 4 groups: basal
      (euthanized at 6 weeks of age), exercise (1 h/d; 5 d/wk), sham exercise (sham),
      and non-treated controls (n = 8 per group). After 6 weeks of treatment, an
      intraperitoneal glucose tolerance test was performed and animals were euthanized
      for tissue analysis. By 5 weeks of treatment, controls had elevated fed and
      fasted glycemia (>11.1 and 7.1 mmol/L, respectively; both P < .05), whereas
      exercise and sham rats remained euglycemic. At euthanasia, there were elevations
      in fed insulin levels in exercise and sham rats compared with basal animals (both
      P < .05). Despite improvements in fed and fasting glucose levels in sham rats,
      glucose tolerance in sham-treated rats (intraperitoneal glucose tolerance test)
      was similar to controls, whereas glucose levels were similar in exercised trained
      and basal rats. After 6 weeks, gastrocnemius glycogen content was higher in
      exercised rats and sham rats when compared with age-matched controls, whereas
      muscle glucose transporter 4 levels were similar between groups. Compared with
      controls, the exercise group had increased beta cell proliferation, beta cell
      mass, and partial maintenance of normal islet morphology. Sham rats also
      displayed beta cell compensation, as evidenced by increased fasting insulin
      levels and partial preservation of normal islet morphology. Finally, at the time
      of euthanasia, plasma corticosterone was increased in sham and control rats but
      was at basal levels in the exercise group. In summary, both exercise and sham
      treatment delay the progression of type 2 diabetes mellitus in the male ZDF rat
      by distinct mechanisms related to pancreatic function and improvements in
      peripheral glucose disposal.

PMID- 17512305
TI  - Cholesteryl ester transfer protein B1B1 genotype as a predictor of coronary
      artery disease in Taiwanese with type 2 diabetes mellitus.
AB  - Diabetes is known to be a high-risk factor for coronary artery disease (CAD), and
      lipid abnormalities have been found to possibly contribute to CAD in diabetic
      patients. Cholesteryl ester transfer protein (CETP) gene TaqIB polymorphism is
      associated with lipid profile variability, and this polymorphism may be a risk
      factor for CAD in diabetic patients. To clarify the relationship between CETP
      TaqIB gene polymorphism and CAD, we enrolled in our study 365 Taiwanese with type
      2 diabetes mellitus (101 with CAD and 264 without CAD). The genotype of the
      subjects for TaqIB polymorphism of CETP in intron 1 was analyzed by using
      polymerase chain reaction-restriction fragment length polymorphism. The CETP B1B1
      genotype (18.8% vs 8.5%, P = .002) and B1 allele (42.1% vs 29.7%, P = .002) were
      significantly more frequent in diabetic patients with CAD than those without CAD.
      Logistic regression analysis revealed that the CETP B1B1 genotype was associated
      with CAD in patients with type 2 diabetes mellitus (odds ratio, 3.18; 95%
      confidence interval, 1.54-6.54; P = .002). Interestingly, in diabetic patients,
      serum creatinine levels higher than 1.4 mg/dL were also associated with increased
      risk for CAD (odds ratio, 2.09; 95% confidence interval, 1.12-3.91; P = .02). Our
      results suggest that the CETP B1B1 genotype is a strong genetic predictor of CAD
      in Taiwanese with type 2 diabetes mellitus.

PMID- 17512306
TI  - Serum uric acid and leptin levels in metabolic syndrome: a quandary over the role
      of uric acid.
AB  - This study investigates the impact of uric acid (UA) on the risk factors
      associated with metabolic syndrome. In addition, this study explores the
      relationship between UA and insulin resistance and serum leptin levels in
      metabolic syndrome. A total of 470 subjects (252 women and 218 men) were
      recruited from the Department of Health Management at Chang Gung Medical Center
      (Linkou, Taiwan). Metabolic syndrome was defined using a modified Adult Treatment
      Panel III (ATP III) definition. The formula for the homeostasis model assessment
      of insulin resistance (HOMA-IR) is as follows: fasting serum insulin (microU/mL)
      x fasting plasma glucose (mmol/L)/22.5. Diabetes mellitus was diagnosed in 45
      subjects (9.6%); 82 subjects (17.4%) had hypertension. Hyperuricemia was
      diagnosed in 144 subjects (30.6%). Of these subjects, 115 (63 females and 52
      males) (24.5%) were diagnosed as having metabolic syndrome. Patients with
      hyperuricemia had increased body mass index, waist-to-hip ratio, and triglyceride
      (Tg) level. The subjects also had lower high-density lipoprotein and greater
      hypertension. Hormone assays showed an elevation of leptin, immunoreactive
      insulin (IRI), and HOMA-IR in the hyperuricemia group. Uric acid appeared to be
      better correlated with Tg, blood pressure (both systolic and diastolic), obesity,
      immunoreactive insulin, and HOMA-IR. Uric acid did not correlate with leptin or
      blood glucose levels. Metabolic syndrome and Tg/high-density lipoprotein ratio
      showed a statistically significant difference in HOMA-IR using 3.8 as a cutoff
      value. Otherwise, there was no difference in leptin value. In conclusion, serum
      UA is significantly related to risk factors of metabolic syndrome except for
      blood glucose. Waist-to-hip ratio and HOMA-IR were statistically different in
      subjects with and without metabolic syndrome.

PMID- 17512308
TI  - The adiponectin-to-leptin ratio in women with polycystic ovary syndrome: relation
      to insulin resistance and proinflammatory markers.
AB  - Central adiposity plays an important role in the insulin resistance of the
      polycystic ovary syndrome (PCOS) through the dysregulated production of various
      adipokines. Polycystic ovary syndrome has also been described as a low-grade
      inflammation state characterized by elevated levels of C-reactive protein (CRP).
      Furthermore, CRP is a strong independent predictor of the metabolic syndrome and
      cardiovascular disease. Recently, the adiponectin-to-leptin (A/L) ratio has been
      proposed as a potential atherogenic index in obese type 2 diabetic patients. The
      aim of this study was to evaluate the potential role of the A/L ratio in the
      metabolic and proinflammatory phenotype of PCOS. We studied 74 Greek women with
      PCOS (38 normal-weight and 36 overweight-obese women). The A/L ratio was
      negatively correlated with BMI (r = -0.79 P < .001), homeostasis model assessment
      (r = -0.642, P < .001), triglycerides (r = -0.67, P < .001), and total
      cholesterol (r = -0.38, P < .01), and positively correlated with high-density
      lipoprotein cholesterol (r = 0.38, P < .01) and sex hormone-binding globulin (r =
      0.39, P = .001). After controlling for BMI, the A/L ratio was independently
      associated with insulin resistance indexes and triglycerides. Furthermore, the
      A/L ratio was negatively correlated with CRP (r = -0.746, P < .0001). Multiple
      regression analysis revealed that BMI and the A/L ratio were the only independent
      significant determinants of CRP (beta = .436, P = .003 and beta = -.398, P =
      .007, respectively). Studying normal-weight and overweight-obese women
      separately, we found an independent association between the A/L ratio and CRP in
      both groups (beta = -.460, P = .009 in normal-weight women and beta = -.570, P =
      .001 in overweight-obese women). In conclusion, the A/L ratio may serve as a
      biomarker of both insulin resistance and low-grade inflammation, providing the
      link between these cardiovascular risk factors in women with PCOS.

PMID- 17512307
TI  - Association analyses of adrenergic receptor polymorphisms with obesity and
      metabolic alterations.
AB  - Genes involved in the regulation of catecholamine function may be important in
      obesity because of the role catecholamines play in energy expenditure and
      lipolysis. To determine if common single nucleotide polymorphisms (SNPs) in
      beta(1)-adrenergic receptor (ADRB1), beta(2)-adrenergic receptor (ADRB2), beta(3)
      adrenergic receptor (ADRB3), and alpha(2)-adrenergic receptor (ADRA2A) genes
      associate with obesity and metabolic alterations, we recruited 74 healthy African
      American and 161 white men and women (age, 18-49 years) to participate in this
      case-control genetic association study. Genotypes were determined by polymerase
      chain reaction and restriction fragment length polymorphism. Associations between
      genotype and body mass index (BMI), percentage of body fat (by measuring skinfold
      thickness in 7 different sites), fasting (12-hour) plasma glucose, insulin,
      potassium concentrations, glycated hemoglobin, and insulin resistance
      (homeostasis model assessment [HOMA(IR)] score) were performed. Among whites, the
      ADRB1 Arg389-->Gly variant associated with insulin concentrations and HOMA(IR):
      mean +/- SD values for insulin and HOMA(IR) in Arg389 homozygotes and carriers of
      the Gly were 10 +/- 7.0 and 12 +/- 9.4 micro IU/mL (P = .02) and 2.1 +/- 1.7 and
      2.6 +/- 2.2 (P = .057), respectively. Systolic blood pressure was higher in
      whites for carriers of the ADBR1 Ser49 compared to Gly49 homozygotes (124 +/-
      12.6 vs 119 +/- 11.3 mm Hg, respectively; P = .02). Subsequent analysis revealed
      that these associations were attributable to a higher BMI among obese
      participants. The ADRA2A G1780A SNP associated with BMI and percentage of body
      fat in African Americans (P = .05). Interactions were detected between ADRA2A C
      1291G and ADRB2 Gln27-->Glu variants for obesity in African Americans and between
      ADRA2A C-1291G SNP and ADBR1 haplotype for obesity in whites. We conclude that
      common SNPs in adrenergic receptor genes may be important susceptibility loci for
      obesity and related alterations. Because of the limited size of our populations,
      our results should be interpreted with caution and should be replicated in larger
      populations.

PMID- 17512309
TI  - Effects of genetic variation in the visfatin gene (PBEF1) on obesity, glucose
      metabolism, and blood pressure in children.
AB  - Visfatin is a peptide predominantly expressed in visceral adipose tissue and was
      hypothesized to be related to obesity and insulin resistance. In the present
      study, we investigated the effects of genetic variations in the visfatin gene
      (pre-B-cell colony-enhancing factor 1 [PBEF1]) on obesity, metabolic parameters,
      and blood pressure (BP) in 2 children cohorts. We genotyped 3 representative
      single nucleotide polymorphisms (rs9770242, -948G>T, rs4730153) in 731
      schoolchildren and in an independent cohort of 167 obese children. There was no
      association of any of the 3 polymorphisms or their haplotypes with body mass
      index (BMI), waist-to-hip ratio, or parameters of glucose, insulin, or lipid
      metabolism in either cohort. However, the -948G variant was associated with
      significantly higher diastolic BP in obese children (P < .05 after adjusting for
      age, sex, pubertal stage, and height). Haplotype analyses confirmed the [T-G-A]
      haplotype to be significantly related to increased diastolic BP in both
      schoolchildren and obese children. In conclusion, genetic variants in PBEF1 may
      be associated with increased BP in children but are not likely to contribute
      significantly to the variation in body mass index and glucose, insulin, or lipid
      metabolism.

PMID- 17512310
TI  - The effects of a glucose load and sympathetic challenge on autonomic function in
      obese women with and without type 2 diabetes mellitus.
AB  - This study examined the effect of glucose ingestion on cardiac autonomic function
      in nonobese women and obese women with and without type 2 diabetes mellitus.
      Heart rate variability was measured via continuous electrocardiogram, and beat-by
      beat blood pressure was recorded using finger photoplethysmography (Portapres,
      TNO Biomedical Instrumentation, Amsterdam, The Netherlands) in a fasted state and
      in response to a 75-g glucose load in 42 middle-aged women (40-60 years). Upright
      tilt was also used as an orthostatic stress to provide a clinically relevant
      challenge to the cardiovascular system. Significant main effects for log
      transformed (Ln) total power (TP, square milliseconds) were observed with upright
      tilt (P < .01) and glucose challenge (P < .05). LnTP decreased in all groups in
      both the fasted and fed state with upright tilt (P < .01), but glucose ingestion
      resulted in higher LnTP in the supine position only (P = .008). Tilt resulted in
      a significant main effect for low-frequency (LFnu, calculated in normalized
      units) and high-frequency (HFnu, calculated in normalized units) power (P <
      .000), whereas the glucose challenge had no effect on LFnu or HFnu power. LFnu
      approached significance for group differences (P = .07), such that the nonobese
      had lower LF power than either of the obese groups. Sympathovagal balance
      (LnLF/HF ratio) was affected by position (P < .000) and group (P < .05), with a
      lower LnLF/HF in the nonobese than in the obese women. Baroreceptor sensitivity
      decreased (P < .01) during upright tilt but was not changed by the glucose
      challenge. In conclusion, basal sympathovagal balance is higher in obese
      individuals with and without type 2 diabetes mellitus. Women with type 2 diabetes
      mellitus showed no differences in autonomic function with an orthostatic
      challenge or glucose load than nondiabetic, obese women. The glucose load did
      alter total spectral power in all of these middle-aged women but had no impact on
      baroreceptor sensitivity.

PMID- 17512311
TI  - 13-cis-Retinoic acid therapy induces insulin resistance, regulates inflammatory
      parameters, and paradoxically increases serum adiponectin concentration.
AB  - 13-cis-Retinoic acid treatment causes insulin resistance and disturbances in
      lipid and glucose metabolism. We studied how 13-cis-retinoic acid affects
      inflammatory factors and adiponectin. A total of 23 healthy patients (age, 24.9
      +/- 0.9 years; body mass index, 22.6 +/- 0.7 kg/m(2)) who received 13-cis
      retinoic acid treatment of acne participated in the study. The patients were
      studied before the treatment, after 3 months of therapy, and 1 month after the
      treatment. Inflammatory parameters were measured, and a 4-hour oral glucose
      tolerance test was performed at each visit. Treatment with 13-cis-retinoic acid
      resulted in a significantly elevated serum adiponectin concentration (from 24.9
      +/- 2.5 to 29.4 +/- 3.6 mg/L, P < .05), hemoglobin A(1c) (from 5.27% +/- 0.05% to
      5.42% +/- 0.06%, P < .01), C-peptide area under the curve (from 314.2 +/- 16.6 to
      350.0 +/- 21.0 (nmol . min)/L, P < .05), and triglycerides (from 0.97 +/- 0.06 to
      1.29 +/- 0.10 mmol/L, P < .05), whereas high-density lipoprotein cholesterol
      decreased (from 1.50 +/- 0.07 to 1.38 +/- 0.08 mmol/L, P < .05). The increase in
      adiponectin during 13-cis-retinoic acid therapy correlated with baseline
      triglycerides (r = 0.51, P < .02). Many inflammatory markers, which were
      nonsignificantly elevated during therapy, decreased significantly after cessation
      of treatment. These were C-reactive protein (median from 1.78 to 1.23 mg/L, P <
      .05), soluble intercellular adhesion molecule 1 (from 210 +/- 10 to 204 +/- 10
      microg/L, P < .02), ceruloplasmin (256 +/- 17 to 231 +/- 17 microg/L, P < .02),
      and erythrocyte sedimentation rate (from 6.4 +/- 1.3 to 4.7 +/- 0.9 mm/h, P <
      .02). Interleukin 6 concentration was unaffected by the therapy, but decreased
      significantly after the treatment (from 2.18 +/- 0.46 to 1.65 +/- 0.43 ng/L, P <
      .05). In conclusion, although treatment with 13-cis-retinoic acid results in
      disturbances in glucose and lipid metabolism, paradoxically serum adiponectin
      concentration increases. 13-cis-Retinoic acid has profound effects on the
      regulation of inflammatory markers.

PMID- 17512312
TI  - Persistent elevation of liver function enzymes within the reference range is
      associated with increased cardiovascular risk in young adults: the Bogalusa Heart
      Study.
AB  - Elevations in alanine aminotransferase (ALT) and gamma-glutamyl transferase
      (GGT), markers of liver dysfunction and nonalcoholic fatty liver, are considered
      as part of the metabolic syndrome and related diseases. However, information is
      limited regarding the persistence (tracking) in levels of these enzymes over time
      and their influence on cardiovascular (CV) risk in young adults. The study sample
      consisted of white and black subjects (N = 489, 40% male, 73% white; baseline
      age, 18-32 years) followed over a period of 12 years as part of the Bogalusa
      Heart Study, with repeat measurements of CV risk factor variables and liver
      enzymes. Both at baseline and follow-up, males vs females had higher ALT (P < .01
      to .0001) and GGT (P < .0001); blacks vs whites had higher GGT (P < .0001). With
      respect to persistence in enzyme levels over time, of those individuals who had
      ALT and GGT at the top quintile specific for age, race, and sex at baseline,
      about 50% of them continued to remain so with high values after 12 years.
      Individuals with levels persistently in the highest quintile vs those in the
      lowest quintile showed higher (P < .0001) body mass index, waist circumference,
      triglycerides, low-density lipoprotein cholesterol, glucose, insulin, insulin
      resistance index, and systolic and diastolic blood pressures; lower (P < .0001)
      high-density lipoprotein cholesterol; and higher (P < .05 to .001) prevalence of
      obesity, hypertension, dyslipidemia, metabolic syndrome as defined by the
      National Cholesterol Education Program Adult Treatment Panel III, positive
      parental history of type 2 diabetes, and coronary heart disease. In addition,
      based on a multivariate analysis using 2 separate models for ALT and GGT,
      baseline levels of both enzymes were independent predictors of follow-up; insulin
      resistance index and baseline GGT were also predictive of follow-up systolic
      blood pressure. Elevations in liver enzymes ALT and GGT, within "reference"
      range, persist over time and relate to clinically relevant adverse CV risk
      profile in young adults.

PMID- 17512313
TI  - Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1
      in obese children and adolescents.
AB  - Matrix metalloproteinases (MMPs) have been implicated in the atherosclerotic
      process and risk factors for the disease such as hypertension, hyperlipidemia, or
      diabetes mellitus in adults. So far, circulating levels of MMPs and their tissue
      inhibitors (TIMPs) have not been assessed in children and adolescents with
      obesity, a known risk factor for cardiovascular disease. Plasma levels of MMP-9
      and TIMP-1 were measured immunoenzymatically in 45 obese children and
      adolescents, aged 15 +/- 1.8 years. The control group consisted of 28 healthy
      children, aged 14.5 +/- 2.5 years. MMP-9 and TIMP-1 concentrations were higher in
      obese children than in the control group (MMP-9: 553.5 +/- 311 vs 400.4 +/- 204
      ng/mL, respectively; P = .02; TIMP-1: 161.2 +/- 32 vs 143.1 +/- 20.1 ng/mL,
      respectively; P = .03). We found significantly higher levels of MMP-9 in obese
      children with coexisting hypertension than in obese normotensive patients (635 +/
      308 vs 450 +/- 289 ng/mL, respectively; P = .04). MMP-9 correlated with body
      mass index (BMI) (r = 0.33, P = .005) and fasting insulin (r = 0.3, P = .013);
      TIMP-1 correlated with BMI (r = 0.35, P = .006). In the group of obese
      hypertensive children (n = 25), MMP-9 correlated with BMI (r = 0.41, P = .001),
      systolic blood pressure (r = 0.41, P = .002), fasting insulin (r = 0.37, P =
      .006), and homeostasis model assessment index of insulin resistance (r = 0.27, P
      = .03). TIMP-1 correlated with BMI (r = 0.33, P = .025) and systolic (r = 0.38, P
      = .008) and diastolic (r = 0.47, P = .001) blood pressure. In the regression
      models, MMP-9 was found to be dependent on fasting insulin (R(2) = 0.16, P =
      .04), and TIMP-1 on BMI (R(2) = 0.14, P = .04). In the obese hypertensive group,
      TIMP-1 was dependent on diastolic blood pressure (R(2) = 0.18, P = .04). Obese
      children and adolescents have elevated plasma concentrations of MMP-9 and TIMP-1.
      Coexistence of hypertension may exacerbate alterations of extracellular matrix
      turnover in these patients. It might be hypothesized that elevated MMP and TIMP
      concentrations may be related to increased cardiovascular risk in obese and
      particularly in obese hypertensive children and adolescents.

PMID- 17512314
TI  - Association of UCP2 and UCP3 gene polymorphisms with serum high-density
      lipoprotein cholesterol among Korean women.
AB  - Decreased serum high-density lipoprotein (HDL-C) cholesterol is a major risk
      factor for atherosclerosis and vascular disease. In this study, we assessed the
      association of 10 uncoupling protein (UCP) 2 and UCP3 polymorphisms with serum
      HDL cholesterol levels and atherogenic indexes among 658 Korean women. Among the
      10 single nucleotide polymorphisms (SNPs) in the UCP2 and UCP3 genes, 2 SNPs in
      UCP2, -866G>A and +4787C>T (A55V) that were tightly linked (r(2) = 0.97), were
      significantly associated with decreased HDL cholesterol levels after Bonferroni
      correction (P = .003 in the recessive model). +4589C>T (Y210Y) in UCP3, a silent
      variation of Tyr210Tyr in exon 5, was also significantly associated with HDL
      cholesterol after multiple comparison correction. These 3 SNPs also exhibited
      some association with increases in the atherogenic index. Source-of-variation
      analysis revealed that -866G>A SNP accounted for 8.09% of the variation in serum
      HDL cholesterol levels independent of body mass index. We believe that our
      results may provide clues to the association of UCP genes with the risk of
      atherosclerosis through their effects on HDL cholesterol.

PMID- 17512315
TI  - The effect of vagal cooling on canine hepatic glucose metabolism in the presence
      of hyperglycemia of peripheral origin.
AB  - We examined the role of vagus nerves in the transmission of the portal glucose
      signal in conscious dogs. At time 0, somatostatin infusion was started along with
      intraportal insulin and glucagon at 4-fold basal and basal rates, respectively.
      Glucose was infused via a peripheral vein to create hyperglycemia ( approximately
      2 fold basal). At t = 90, hollow coils around the vagus nerves were perfused with
      -10 degrees C or 37 degrees C solution in the vagally cooled (COOL) and sham
      cooled (SHAM) groups, respectively (n = 6 per group). Effectiveness of vagal
      blockade was demonstrated by increase in heart rate during perfusion in the COOL
      vs SHAM groups (183 +/- 3 vs 102 +/- 5 beats per minute, respectively) and by
      prolapse of the third eyelid in the COOL group. Arterial plasma insulin (22 +/- 2
      and 24 +/- 3 micro U/mL) and glucagon (37 +/- 5 and 40 +/- 4 pg/mL)
      concentrations did not change significantly between the first experimental period
      and the coil perfusion period in either the SHAM or COOL group, respectively. The
      hepatic glucose load throughout the entire experiment was 46 +/- 1 and 50 +/- 2
      mg . kg(-1) . min(-1) in the SHAM and COOL groups, respectively. Net hepatic
      glucose uptake (NHGU) did not differ in the SHAM and COOL groups before (2.2 +/-
      0.5 and 2.9 +/- 0.8 mg . kg(-1) . min(-1), respectively) or during the cooling
      period (3.0 +/- 0.5 and 3.4 +/- 0.6 mg . kg(-1) . min(-1), respectively).
      Likewise, net hepatic glucose fractional extraction and nonhepatic glucose uptake
      and clearance were not different between groups during coil perfusion.
      Interruption of vagal signaling in the presence of hyperinsulinemia and
      hyperglycemia resulting from peripheral glucose infusion did not affect NHGU,
      further supporting our previous suggestion that vagal input to the liver is not a
      primary determinant of NHGU.

PMID- 17512316
TI  - Insulin resistance and self-rated symptoms of depression in Swedish women with
      risk factors for diabetes: the Women's Health in the Lund Area study.
AB  - Previous studies have suggested that depression increases the risk for diabetes
      and that this may be mediated through insulin resistance. The study aimed to
      analyze if self-rated symptoms of depression are related to insulin resistance
      among middle-aged and older Swedish women with features of the metabolic syndrome
      and being at risk for type 2 diabetes mellitus. We analyzed data from 1047
      Swedish women aged 50 to 64 years without a history of diabetes and living in the
      southern part of Sweden. A variable self-rated symptoms of depression (SRSD) was
      defined by using the Gothenburg Quality of Life instrument. We estimated odds
      ratios (ORs) to determine whether or not SRSD was associated with the homeostasis
      model assessment of insulin resistance. The variable SRSD was not associated with
      insulin resistance. However, it was positively associated with waist-hip ratio
      (OR, 1.95; 95% confidence interval, 1.28-3.00) and negatively associated with
      physical exercise (OR, 1.29; 95% confidence interval, 0.99-1.68) after
      multivariate adjustment. In conclusion, lifestyle factors such as physical
      inactivity and abdominal obesity, but not insulin resistance, seem to be related
      to self-rated symptoms of depression in women with risk factors for diabetes
      mellitus. The relationship between insulin resistance and major depression needs
      to be further examined.

PMID- 17512317
TI  - Addition of medroxyprogesterone acetate to conjugated equine estrogens results in
      insulin resistance in adipose tissue.
AB  - The purpose of this study was to determine if the insulin resistance we have
      previously reported in surgically postmenopausal primates treated with combined
      hormone therapy (HT) is due in part to effects on adipose tissue. Eighty-seven
      ovariectomized monkeys were fed a moderately atherogenic diet (0.28 mg
      cholesterol per kilocalorie [0.07 mg/kJ]) and randomized to receive no hormones
      (control, n = 29), estrogen therapy (ET, conjugated equine estrogens, 0.625 mg/d
      human equivalent; n = 29), or HT (ET + medroxyprogesterone acetate, 2.5 mg/d
      human equivalent; n = 29) in the diet for 2 years. Fasting glycemic measures were
      made at baseline and at the end of treatment. Circulating adiponectin measures,
      insulin tolerance tests, glucose tolerance tests, and isolated adipocyte glucose
      uptake assays were performed at the end of the trial. Hormone therapy-treated
      animals were insulin resistant, as determined by greater fasting insulin
      concentrations (P = .008), greater homeostasis model assessment of insulin
      resistance (HOMA-R) value (P = .005) and slower glucose disposal after insulin
      administration (K(ITT); P = .02) when compared with controls. Subcutaneous
      adipocytes from HT-treated monkeys had a greater ED(50) for insulin (P = .04) and
      lower maximal glucose uptake per cell (P < .001) compared with controls,
      suggesting impaired adipocyte insulin sensitivity. Adipocytes were smaller (P =
      .001) and adiponectin concentrations were greatest in the ET group (P = .02),
      with no difference between controls and HT-treated monkeys. In conclusion,
      estrogen therapy resulted in smaller adipocyte size and greater adiponectin
      concentrations than control or HT. Hormone therapy resulted in impaired insulin
      sensitivity and adipocyte glucose uptake compared with controls, whereas there
      was no difference between ET and controls. Because no adverse effects were found
      with ET alone, it is likely that the progestin, medroxyprogesterone acetate,
      resulted in the negative effects of the combined HT regimen on whole-body insulin
      sensitivity, which were mediated, in part, by reductions in adipose tissue
      responses to insulin.

PMID- 17512318
TI  - Nuclear magnetic resonance-determined lipoprotein abnormalities in nonhuman
      primates with the metabolic syndrome and type 2 diabetes mellitus.
AB  - The lipid profile in patients with the metabolic syndrome (MetS) and type 2
      diabetes mellitus (T2DM) is commonly characterized by increased levels of
      triglycerides and decreased levels of high-density lipoprotein (HDL) cholesterol.
      However, within each lipoprotein class, the changes are more complex. The present
      study defined the characteristics of dyslipidemia among nonhuman primates, using
      nuclear magnetic resonance (NMR) spectroscopy as well as the classic beta
      quantification method, and examined the pattern of multiple lipoprotein fractions
      in relation to the main factors identified with the MetS. Seventy-three rhesus
      monkeys were classified into 3 groups: healthy monkeys, monkeys with MetS, and
      monkeys with T2DM. Characteristics of dyslipidemia in the MetS and T2DM groups
      included increased levels of triglyceride-rich very low-density lipoprotein,
      intermediate-density lipoprotein, and small, dense, low-density lipoprotein (LDL)
      particles. Reduced concentrations of large LDL and large HDL particles together
      with reduction of LDL and HDL particle sizes were also observed. Correlation
      analysis revealed that poor glycemic and lipid profiles, glucose intolerance, and
      insulin resistance were associated with an atherogenic NMR profile. Compared with
      the conventional lipid panel, the NMR lipoprotein profile presented in greater
      detail distinctive differences between the dyslipidemia of the MetS and that of
      diabetes and demonstrated significant and divergent shifts in both particle size
      and number within lipoprotein classes between those 2 groups. Detailed
      lipoprotein profiling may provide additional indicators for more timely
      intervention. Rhesus monkeys are likely to provide an excellent model for novel
      drug testing designed to address the specific differences in lipoprotein fraction
      profile across these 3 groups that reflect the progression of pathophysiology
      from normal to overt diabetes.

PMID- 17512319
TI  - Characteristics of lipolysis in white adipose tissues of SHR/NDmc-cp rats, a
      model of metabolic syndrome.
AB  - This study shows the characteristics of hormone-dependent lipolysis in white
      adipose tissues from corpulent spontaneously hypertensive rats (SHR/NDmc
      cp(cp/cp)). The glycerol-releasing activity on addition of norepinephrine (NE)
      and corticotropin (ACTH) was diminished in slices of epididymal, retroperitoneal,
      and mesenteric adipose tissues from cp/cp rats compared with those from Wistar
      Kyoto rats and lean spontaneous hypertensive rats (SHR/NDmc-cp(+/+)). 8-Bromo
      cyclic adenosine monophosphate had a slight effect on lipolysis in epididymal,
      retroperitoneal, and mesenteric adipose tissues from cp/cp rats, and addition of
      NE and ACTH resulted in a slight accumulation of cyclic adenosine monophosphate
      in epididymal adipose tissue from cp/cp rats. Therefore, the alteration of
      hormone-dependent lipolysis-related genes was analyzed using quantitative real
      time polymerase chain reaction. It was found that the expression of beta(3)
      adrenergic receptor, melanocortin 2 receptor, hormone-sensitive lipase, and
      perilipin messenger RNAs was limited in epididymal, retroperitoneal, mesenteric,
      and subcutaneous adipose tissues from cp/cp rats compared with +/+ rats. These
      results indicate that in white adipose tissue from cp/cp rats, the diminished
      lipolytic response to NE and ACTH may be caused by impaired expression of beta(3)
      adrenergic receptor, melanocortin 2 receptor, hormone-sensitive lipase, and
      perilipin.

PMID- 17512320
TI  - Early-phase insulin secretion is disturbed in obese subjects with glucose
      intolerance.
AB  - The loss of early-phase insulin secretion is a characteristic feature of type 2
      diabetes mellitus. The aim of this study is to examine when impairment of early
      phase insulin secretion occurs and whether it can be related to increase in
      insulin resistance caused by obesity. We developed an analytical method to
      qualify the early-phase insulin secretion; that is, we measured C-peptide
      immunoreactivity (CPR) response to a selective increase in blood glucose level in
      portal vein during oral glucose load under a euglycemic hyperinsulinemic clamp
      (clamp-OGL). Glucose infusion rate, hepatic glucose uptake, and CPR response
      during clamp-OGL were measured in 30 subjects with diabetes who were divided into
      3 groups based on body mass index, 13 obese subjects with normal glucose
      tolerance (O-NGT), 10 obese subjects with impaired glucose tolerance (O-IGT), and
      15 healthy subjects. Significant increase in CPR levels at 10 minutes in clamp
      OGL compared with those at steady state was observed in healthy subjects and in O
      NGT; however, those were small or absent in diabetic patients and in O-IGT. The
      incremental ratio of CPR was not correlated to the makers of insulin resistance.
      The early-phase insulin secretion is well maintained in O-NGT; however, early
      phase insulin secretion has already been disturbed in obese subjects with glucose
      intolerance.

PMID- 17512322
TI  - Research news and notes.

PMID- 17512323
TI  - Microneurosurgical management of distal middle cerebral artery aneurysms.
AB  - BACKGROUND: Distal middle cerebral artery aneurysms originate from branches of
      MCA distal to its main bifurcation or the peripheral branches. Distal middle
      cerebral artery aneurysms are the least frequently seen among the middle cerebral
      artery aneurysms. The purpose of this article is to review the practical anatomy,
      preoperative planning, and avoidance of complications in the microsurgical
      dissection and clipping of MdistAs. METHODS: This review, and the whole series on
      intracranial aneurysms, are 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 10000 aneurysm patients
      since 1951. In the Kuopio Cerebral Aneurysm Database of 3005 patients with 4253
      aneurysms, 69 patients carrying altogether 78 MdistAs formed 5% of all MCA
      aneurysms. Among the 18 patients with ruptured MdistAs (23%), an ICH occurred in
      9 (50%). CONCLUSIONS: Distal middle cerebral artery aneurysms are rare. The
      microneurosurgical treatment of MdistAs is challenging. They are often difficult
      to localize during the operation, and lack of collateral circulation makes their
      occlusion more demanding. High rate of ICH and high tendency of rebleeding urge
      acute or emergency surgery in most of ruptured cases. Microneurosurgical clipping
      is the most effective treatment of MdistAs.

PMID- 17512324
TI  - Is the image guidance of ultrasonography beneficial for neurosurgical routine?
AB  - BACKGROUND: Intraoperative US has been widely used in neurosurgical procedures.
      However, images are often difficult to read. In the present study, we evaluate
      whether the image guidance of ultrasonography is helpful for the interpretation
      of US scans. METHODS: Twenty-nine patients with tumor were operated on with the
      aid of intraoperative US from January to June 2005. Image-guided sonography was
      used in 13 cases and nonnavigated US technology in the remaining cases. We
      compared the 2 technologies retrospectively. RESULTS: Although image quality was
      good in most cases, orientation remained difficult in 8 of the 16 patients where
      conventional sonography was used. With the aid of image fusion for navigated
      sonography, the orientation was judged superior to nonnavigated US. CONCLUSION:
      In our experience, integration of the US into the navigation system facilitates
      anatomical understanding. Thus, we feel that this technology is beneficial for
      neurosurgical routine.

PMID- 17512326
TI  - Image fusion of fluid-attenuated inversion recovery magnetic resonance imaging
      sequences for surgical image guidance.
AB  - BACKGROUND: Nonenhancing brain lesions can be relatively poorly defined on
      volumetric data sets routinely used for surgical guidance. Fluid-attenuated
      inversion recovery MRI sequences can provide better margin visualization of
      nonenhancing or poorly enhancing lesions. METHODS: Using image fusion programs,
      we combined data sets of SPGR imaging pulse sequence or volumetric CT with
      volumetrically acquired FLAIR sequences and subsequently used the fused data set
      for image-guided surgery. This technique was used in 50 surgical cases. Of these,
      9 were nonenhancing intrinsic brain tumors, 13 were partially enhancing tumors,
      and 11 were enhancing tumors. In addition, FLAIR fusion was selectively used for
      6 nontumoral lesions and in 11 nonlesional epilepsy surgery cases. RESULTS: Image
      guidance using the fused data set was accurate in all 50 cases. Despite the lack
      of enhancement, 3 of the 9 nonenhancing tumors were found to be high grade. One
      of the low-grade tumors was associated with considerable areas of gliotic change
      not considered to represent tumor on permanent histology. In all other cases, the
      FLAIR-bright resected margins were consistent with tumor, not gliosis. Radical
      resection (>95% volume) was achieved in 21 of 23 tumor cases in which this had
      been the preoperative intent. CONCLUSIONS: Nonenhancing lesions are often poorly
      demarcated not only on imaging studies, but also during surgery. Fluid-attenuated
      inversion recovery fusion allows resection of such lesions using intraoperative
      computer image guidance. Complementary FLAIR information can also occasionally be
      useful during surgical approaches to enhancing lesions or in nontumor cases. It
      must be kept in mind that FLAIR has high sensitivity but low specificity. Fluid
      attenuated inversion recovery abnormalities do not obviate the need for mapping
      in potentially functional areas.

PMID- 17512328
TI  - Clinical manifestations and surgical results for paraclinoid cerebral aneurysms
      presenting with visual symptoms.
AB  - BACKGROUND: Clipping a paraclinoid aneurysm is difficult if the patient has a
      visual disturbance. Visual function sometimes deteriorates postoperatively for
      patients with a large aneurysm. In this study, we report the long-term follow-up
      of patients with visual impairments attributed to optic nerve compression when
      paraclinoid aneurysms are surgically treated. METHODS: Seventeen patients with
      optic nerve impairment induced by compression of paraclinoid ICA aneurysms were
      treated. All of the aneurysms were large, including 6 giant aneurysms. The
      aneurysms displayed partial thrombosis or calcification of the aneurysmal wall in
      6 cases. RESULTS: Direct surgery such as neck clipping or wrapping of the
      aneurysm was performed in 9 aneurysms and indirect procedures in 8 others (ICA
      occlusion, 1; ICA occlusion + bypass, 7). Of 17 patients, 11 (65%) showed
      improvement in several dysfunctions of visual acuity or visual field. Of 6
      patients, whose vision had not recovered well, 5 underwent direct surgery.
      Moreover, these 5 patients had an intra-aneurysmal thrombosis or calcification of
      the aneurysmal wall. Nevertheless, 1 patient whose aneurysm with partial
      thrombosis was treated via indirect procedure had good recovery of vision.
      CONCLUSIONS: Direct clipping is the treatment of choice for patients with a mass
      effect on the optic nerve due to paraclinoid aneurysm. However, it is difficult
      to achieve sufficient decompression of the optic nerve when the aneurysm is
      accompanied by partial thrombosis or calcification of the aneurysmal wall. In
      those cases, an indirect procedure seems to be a relatively safe, effective
      treatment.

PMID- 17512331
TI  - Photochemically induced cerebral ischemia in a mouse model.
AB  - BACKGROUND: MCAO has been widely used to produce ischemic brain lesions. The
      lesions induced by MCAO tend to be variable in size because of the variance in
      the collateral blood supply found in the mouse brain. METHODS: We modified the
      rat photothrombosis model for use in mice. Male C57BL/6 mice were subjected to
      focal cerebral ischemia by photothrombosis of cortical microvessels. Cerebral
      infarction was produced by intraperitoneal injection of rose bengal, a
      photosensitive dye, and by focal illumination through the skull. Motor impairment
      was assessed by the accelerating rotarod and staircase tests. The brain was
      perfusion fixed for histologic determination of infarct volume 4 weeks after
      stroke. RESULTS: The lesion was located in the frontal and parietal cortex and
      the underlying white matter was partly affected. A relatively constant infarct
      volume was achieved 1 month after photothrombosis. The presence of the
      photothrombotic lesion significantly impaired the motor performance as measured
      by the rotarod and staircase tests. Our findings show that photothrombotic
      infarction in mice is highly reproducible in size and location. CONCLUSION: This
      procedure can provide a simple model of cerebral infarction for a unilateral
      motor cortex lesion. In addition, it can provide a suitable model for the study
      of potential neuroprotective and therapeutic agents in human stroke.

PMID- 17512333
TI  - Neurosurgical training in Europe, problems and possible solutions.

PMID- 17512343
TI  - Mucocele of the paranasal sinuses as a cause of acquired orbital hypertelorism:
      the second case.
AB  - BACKGROUND: Orbital hypertelorism is defined as a lateralization of the total
      orbit. This condition is associated almost always with congenital abnormalities.
      An acquired total displacement of the orbit is almost impossible once the bony
      pillars of the craniofacial complex are established. The aim of this article was
      to discuss a case of a young man with paranasal sinus mucocele, who developed
      OHT. CASE DESCRIPTION: A 20-year-old man was admitted to us with orbital
      hypertelorism in 1993. The patient's examination revealed marked orbital
      hypertelorism, and no other abnormal finding was noted, and he had no congenital
      defect at birth. Hypertelorism was corrected by surgery, and we find that this
      condition was acquired secondary to paranasal sinus mucocele. CONCLUSION: This is
      the second case of an acquired OHT secondary to paranasal sinus mucocele and the
      first in which the condition was corrected by surgery in late years of life. We
      found excellent correction of orbital hypertelorism 13 years after surgery. The
      authors discuss the possible link between mucocele and possible mechanism for the
      development of orbital hypertelorism and emphasize the need for early surgery and
      long-term follow-up.

PMID- 17512345
TI  - Cranial nerve hemangioblastomas. Report of a rare case and review of literature.
AB  - BACKGROUND: Cranial nerve hemangioblastomas are exceedingly rare lesions. We
      review available literature and present the first surgical report on a solid
      hemangioblastoma arising from the trigeminal nerve and involving the Meckel cave
      that was successfully treated with selective embolization and successive surgical
      resection. CASE DESCRIPTION: A 54-year-old woman presented with an 8-month
      history of facial numbness associated with headache. An MRI revealed a highly
      vascularized supra- and infratentorial mass involving the right Meckel cave. A
      preoperative angiogram with selective embolization of tumoral feeders was
      performed, and the patient elected to undergo surgical treatment. A large solid
      lesion encasing the trigeminal nerve was resected without complications via a
      PLPA approach. Hystopathological examination revealed features consistent with
      the diagnosis of hemangioblastoma. Other stigmata or familiar history of VHL
      disease were absent. CONCLUSIONS: Review of the literature confirms that cranial
      nerve hemangioblastomas are very rare lesions that occur sporadically or in
      association with VHL disease. Surgical management of such lesions should be
      directed by clinical and radiological features as well as patient expectations.

PMID- 17512347
TI  - Intraventricular cryptococcal cysts masquerading as racemose neurocysticercosis.
AB  - BACKGROUND: Cryptococcal infections of the CNS are infrequent in immunocompetent
      hosts. When present, they usually present as meningitis and hydrocephalus or as
      fungal masses called cryptococcomas. We report a case in which intraventricular
      cryptococcal cysts clinically and radiologically simulated the racemose form of
      neurocysticercosis. CASE DESCRIPTION: A 23-year-old man presented to the
      emergency department with a 1-week history of severe headache, dizziness, nausea,
      vomiting, and some lethargy. A computed tomography scan revealed significant
      hydrocephalus. The patient was admitted to the hospital and immediately underwent
      a right ventriculostomy tube placement. CSF examination showed a meningitic
      pattern. Magnetic resonance imaging, including FLAIR images, showed multiple
      large cysts in the temporal horns of both lateral ventricles in addition to
      hydrocephalus. When an endoscopic left temporal cyst fenestration failed to
      decompress his trapped right temporal horn, he underwent placement of a left
      lateral ventricle to peritoneal shunt and a right temporal cyst to peritoneal
      shunt. ELISA test results for HIV-1 and -2 antibodies in the patient's serum were
      negative. His CD4 and CD8 counts were within normal limits. Multiple tests for
      CSF anticysticercal antibody using IgG ELISA gave unequivocally negative results.
      Latex agglutination tests detected Cryptococcus neoformans antigen in his CSF in
      titers of 1:1024, which progressively decreased in response to antifungal
      therapy. The patient underwent treatment with IV amphotericin B for 7 weeks, IV 5
      FC for 2 weeks, and oral fluconazole for 5 weeks. At discharge, 3 consecutive CSF
      cultures were negative for bacteria and fungi. His neurologic status returned to
      baseline. CONCLUSIONS: Cryptococcal CNS infections in immunocompetent hosts can
      mimic the intraventricular form of racemose neurocysticercosis. Distinguishing
      between the two is essential because the medical management of the 2 conditions
      is distinct from each other.

PMID- 17512348
TI  - If you don't know where you are going, you will never get there.

PMID- 17512349
TI  - Sudden cardiac arrest in a successfully embolized case of giant vertebral artery
      aneurysm with hydrocephalus.

PMID- 17512351
TI  - Re: Surgery for intramedullary tuberculoma of the spinal cord: report of 2 cases
      (Muthukumar et al. Surg Neurol 2006;66:69-74).

PMID- 17512352
TI  - The management of recurrent ovarian cancer.

PMID- 17512353
TI  - Plasma concentrations of myeloperoxidase predict mortality after myocardial
      infarction.
AB  - OBJECTIVES: This study investigated relationships between plasma myeloperoxidase
      (MPO), protein oxidation markers, and clinical outcome retrospectively in
      patients after acute myocardial infarction (MI). BACKGROUND: Reactive oxidants
      are implicated in cardiovascular disease, and elevated plasma MPO is reported to
      predict adverse outcome in acute coronary syndromes. METHODS: Detailed
      demographic information, radionuclide ventriculography, neurohormone
      measurements, and clinical history were obtained for 512 acute MI patients at
      hospital admission. Plasma levels of MPO and protein carbonyls were measured in
      patients and 156 heart-healthy control subjects. 3-chlorotyrosine was measured in
      selected patients. Patient mortality was followed for 5 years. RESULTS: Plasma
      MPO and protein carbonyl concentrations were higher in MI patients 24 h to 96 h
      after admission than in control subjects (medians: MPO 55 ng/ml vs. 39 ng/ml, and
      protein carbonyls 48 pmol/mg vs. 17 pmol/mg protein, p < 0.001 for each). Both
      markers were significantly correlated with each other and with cardiovascular
      hormone levels. Chlorotyrosine was not elevated in patients with high MPO or
      carbonyl levels. Above-median levels of MPO but not protein carbonyls were
      independently predictive of mortality (odds ratio 1.8, 95% confidence interval
      1.0 to 3.0, p = 0.034). Patients with above-median MPO levels in combination with
      above-median plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) or
      below-median left ventricular ejection fraction (LVEF) had significantly greater
      mortality compared with other patients. CONCLUSIONS: Myeloperoxidase and protein
      carbonyl levels are elevated in plasma after acute MI, apparently via independent
      mechanisms. High MPO is a risk factor for long-term mortality and adds prognostic
      value to LVEF and plasma NT-proBNP measurements.

PMID- 17512354
TI  - Appraisal of myeloperoxidase for evaluation of patients with suspected acute
      coronary syndromes.

PMID- 17512355
TI  - Low-density lipoprotein-dependent and -independent effects of cholesterol
      lowering therapies on C-reactive protein: a meta-analysis.
AB  - OBJECTIVES: This study sought to assess the contribution of low-density
      lipoprotein (LDL)-dependent and LDL-independent effects of LDL-lowering therapies
      to changes in C-reactive protein (CRP) in healthy or stable subjects. BACKGROUND:
      Correlations of change in LDL and CRP in individuals are lowered by their
      measurement variability. By using average changes in LDL and CRP in study groups,
      meta-analysis reduces this variability to better assess their correlation.
      METHODS: A systematic search for randomized placebo-controlled trials reporting
      change in LDL and CRP with LDL-lowering interventions retrieved 23 studies with
      57 groups treated with a variety of statins, nonstatin drugs, or other regimens.
      Meta-analysis techniques assessed the relationships between average mean
      differences (placebo - treatment) in change in CRP and LDL. RESULTS: The overall
      reduction in CRP was 28% (95% confidence interval 26% to 30%). Significantly
      greater CRP reduction occurred in statin and statin-ezetimibe interventions,
      interventions using 80 mg/day of statins, and with greater LDL lowering. Meta
      regression analysis showed a strong correlation between the change in LDL and CRP
      (r = 0.80, p < 0.001). Statin therapies had no significant effect on CRP after
      adjusting for the change in LDL. In a multivariate model applied to a range of
      LDL reduction typically seen with statins (20% to 60%), 89% to 98% of CRP change
      was related to LDL lowering and 2% to 11% was related to non-LDL effects of
      statins. CONCLUSIONS: In clinical practice, most of the anti-inflammatory effect
      of LDL-lowering therapies is related to the magnitude of change in LDL. The
      potential non-LDL effects of statins on inflammation are much smaller in
      magnitude.

PMID- 17512356
TI  - Statins targeting inflammation by lowering low-density lipoprotein?

PMID- 17512357
TI  - Early adult risk factor levels and subsequent coronary artery calcification: the
      CARDIA Study.
AB  - OBJECTIVES: We sought to determine whether early adult levels of cardiovascular
      risk factors predict subsequent coronary artery calcium (CAC) better than
      concurrent or average 15-year levels and independent of a 15-year change in
      levels. BACKGROUND: Few studies have used multiple measures over the course of
      time to predict subclinical atherosclerosis. METHODS: African American and white
      adults, ages 18 to 30 years, in 4 U.S. cities were enrolled in the prospective
      CARDIA (Coronary Artery Risk Development in Young Adults) study from 1985 to
      1986. Risk factors were measured at years 0, 2, 5, 7, 10, and 15, and CAC was
      assessed at year 15 (n = 3,043). RESULTS: Overall, 9.6% adults had any CAC, with
      a greater prevalence among men than women (15.0% vs. 5.1%), white than African
      American men (17.6% vs. 11.3%), and ages 40 to 45 years than 33 to 39 years
      (13.3% vs. 5.5%). Baseline levels predicted CAC presence (C = 0.79) equally as
      well as average 15-year levels (C = 0.79; p = 0.8262) and better than concurrent
      levels (C = 0.77; p = 0.019), despite a 15-year change in risk factor levels.
      Multivariate-adjusted odds ratios of having CAC by ages 33 to 45 years were 1.5
      (95% confidence interval [CI] 1.3 to 1.7) per 10 cigarettes, 1.5 (95% CI 1.3 to
      1.8) per 30 mg/dl low-density lipoprotein cholesterol, 1.3 (95% CI 1.1 to 1.5)
      per 10 mm Hg systolic blood pressure, and 1.2 (95% CI 1.1 to 1.4) per 15 mg/dl
      glucose at baseline. Young adults with above optimal risk factor levels at
      baseline were 2 to 3 times as likely to have CAC. CONCLUSIONS: Early adult levels
      of modifiable risk factors, albeit low, were equally or more informative about
      odds of CAC in middle age than subsequent levels. Earlier risk assessment and
      efforts to achieve and maintain optimal risk factor levels may be needed.

PMID- 17512358
TI  - Anxiety worsens prognosis in patients with coronary artery disease.
AB  - OBJECTIVES: This study examined the effect of anxiety on mortality and nonfatal
      myocardial infarction (MI) in patients with coronary artery disease (CAD).
      BACKGROUND: Inconsistent data exist regarding the impact of anxiety on the
      prognosis of patients with CAD. METHODS: The authors conducted a prospective
      cohort study at an outpatient cardiology clinic of 516 patients with CAD (mean
      age 68 years at entry, 82% male) by administering the Kellner Symptom
      Questionnaire annually. The primary outcome was the composite of nonfatal MI or
      all-cause mortality. RESULTS: During an average follow-up of 3.4 years, we
      documented 44 nonfatal MIs and 19 deaths. A high cumulative anxiety score was
      associated with an increased risk of nonfatal MI or death. Comparing the highest
      to lowest tertile of anxiety score, the age-adjusted hazard ratio was 1.97 (95%
      confidence interval 1.03 to 3.78, p = 0.04). In a multivariate Cox model after
      adjusting for age, gender, education, marital status, smoking, hypertension,
      diabetes mellitus, previous MI, body mass index, and total cholesterol, each unit
      increase in the cumulative mean anxiety score was associated with increased risk
      of nonfatal MI or total mortality; the hazard ratio was 1.06 (95% confidence
      interval 1.01 to 1.12, p = 0.02). CONCLUSIONS: A high level of anxiety maintained
      after CAD diagnosis constitutes a strong risk of MI or death among patients with
      CAD.

PMID- 17512359
TI  - Central sleep apnea, right ventricular dysfunction, and low diastolic blood
      pressure are predictors of mortality in systolic heart failure.
AB  - OBJECTIVES: The purpose of this study was to determine whether central sleep
      apnea (CSA) contributes to mortality in patients with heart failure (HF).
      BACKGROUND: Cheyne-Stokes breathing with CSA commonly occurs in patients with
      systolic HF. Consequences of CSA, including altered blood gases and neurohormonal
      activation, could result in further left ventricular dysfunction. Therefore, we
      hypothesized that CSA might contribute to mortality of patients with HF. METHODS:
      We followed 88 patients with systolic HF (left ventricular ejection fraction < or
      =45%) with (n = 56) or without (n = 32) CSA. The median follow-up was 51 months.
      RESULTS: The mean (+/-SD) of apnea-hypopnea index was significantly higher in
      patients with CSA (34 +/- 25/h) than those without CSA (2 +/- 1/h). Most of these
      events were central apneas. In Cox multiple regression analysis, 3 of 24
      confounding variables independently correlated with survival. The median survival
      of patients with CSA was 45 months compared with 90 months of those without CSA
      (hazard ratio = 2.14, p = 0.02). The other 2 variables that correlated with poor
      survival were severity of right ventricular systolic dysfunction and low
      diastolic blood pressure. CONCLUSIONS: In patients with systolic HF, CSA, severe
      right ventricular systolic dysfunction, and low diastolic blood pressure might
      have an adverse effect on survival.

PMID- 17512360
TI  - Clinical and electrophysiological spectrum of idiopathic ventricular outflow
      tract arrhythmias.
AB  - OBJECTIVES: This study sought to compare and contrast the clinical and
      electrophysiological characteristics of outflow tract arrhythmias. BACKGROUND:
      Idiopathic ventricular outflow tract arrhythmias manifest clinically in 3 forms:
      1) paroxysmal sustained monomorphic ventricular tachycardia (SMVT), 2) repetitive
      nonsustained ventricular tachycardia (NSVT), or 3) premature ventricular
      contractions (PVCs). Although these arrhythmias have a similar site of origin, it
      is unknown whether they share a common mechanism or similar clinical features.
      METHODS: A total of 127 patients (63 female [50%], mean age 51 +/- 15 years) were
      evaluated for outflow tract arrhythmias. RESULTS: A total of 36 (28%) presented
      with the index clinical arrhythmia of SMVT, 46 (36%) with NSVT, and 45 (35%) with
      PVCs. The sites of origin of the arrhythmias were similar among the 3 groups,
      occurring in the right ventricular outflow tract in 82%. Sustained ventricular
      tachycardia was more likely to be induced during exercise in the SMVT (10 of 15
      patients [67%]) than NSVT or PVCs groups (p < 0.01). Sustained outflow tract
      ventricular tachycardia was induced at electrophysiology study in 78% of SMVT
      patients, 48% of NSVT patients, and 4% of PVCs patients. Adenosine was similarly
      effective in all 3 groups (p = NS). CONCLUSIONS: Patients with outflow tract
      arrhythmias can be differentiated based on the subtype of arrhythmia. However,
      the observation that approximately 50% of patients with NSVT and approximately 5%
      of patients with PVCs have inducible sustained ventricular tachycardia that
      behaves in an identically unique manner to those who present with sustained
      ventricular tachycardia (e.g., adenosine-sensitive) suggests that rather than
      representing distinct entities, outflow arrhythmias may be considered a continuum
      of a single mechanism.

PMID- 17512361
TI  - Diagnostic accuracy of multidetector computed tomography coronary angiography in
      patients with dilated cardiomyopathy.
AB  - OBJECTIVES: The purpose of this work was to assess the safety, feasibility, and
      diagnostic accuracy of multidetector computed tomography (MDCT) in dilated
      cardiomyopathy (DCM) of unknown etiology. BACKGROUND: Multidetector computed
      tomography is an appropriate noninvasive tool for coronary artery disease (CAD)
      detection, particularly in patients with low probability of the disease, such as
      patients with DCM of unknown origin. METHODS: We studied 61 unknown origin DCM
      patients (ejection fraction: 33.9 +/- 8.6%, group 1) and 139 patients with normal
      cardiac function with indications for coronary angiography (group 2, control
      population). All underwent coronary MDCT and angiography. Multidetector computed
      tomography images were acquired by light speed 16-slice computed tomography. The
      degree of stenosis was estimated in 15 coronary artery segments according to the
      American Heart Association model. RESULTS: In group 1, no MDCT-related
      complications were found, while 10 complications were associated with
      conventional angiography (p = 0.001). Overall feasibility of coronary artery
      visualization was 97.2% (863 of 888 segments). The most frequent cause of
      artifacts was interference from a hypertrophic cardiac venous system (10
      artifacts, 40%). In group 2, overall feasibility was 96.1% (p = NS vs. group 1).
      In group 1, all cases with normal (44 cases) or pathological (17 cases) coronary
      arteries by conventional coronary angiography were correctly detected by MDCT,
      with, in 1 case, disparity of stenosis severity. In group 1, sensitivity,
      specificity, and positive and negative predictive values of MDCT for the
      identification of >50% stenosis were 99%, 96.2%, 81.2%, and 99.8%, respectively.
      In group 2, sensitivity and negative predictive values were lower than in group 1
      (86.1% vs. 99% and 96.4% vs. 99.8%, respectively); specificity (96.4%) and
      positive predictive value (86.1%) were not significantly different versus group
      1. CONCLUSIONS: Multidetector computed tomography is feasible, safe, and accurate
      for identification of idiopathic versus ischemic DCM, and may represent an
      alternative to coronary angiography.

PMID- 17512362
TI  - Visualizing the coronaries in patients presenting with heart failure of unknown
      etiology.

PMID- 17512363
TI  - Multiple less common genetic variants explain the association of the cholesteryl
      ester transfer protein gene with coronary artery disease.
AB  - OBJECTIVES: The objective of this study was to identify associations of the
      cholesteryl ester transfer protein (CETP) gene with coronary artery disease (CAD)
      with tagging (t) single nucleotide polymorphisms (SNPs) chosen to optimally
      account for intra-genic variation. BACKGROUND: The CETP gene plays a critical
      role in lipoprotein metabolism, but the common and well-studied TaqIB variant is
      inconsistently predictive of CAD. METHODS: From a deoxyribonucleic acid bank of
      10,020 individuals, nondiabetic nonsmoking patients (n = 4,811) with
      angiographically defined, clinically significant CAD (> or =70% stenosis) or
      normal coronaries were genotyped for 11 CETP tSNPs. Myocardial infarction (MI)
      and lipid levels were evaluated as secondary end points. RESULTS: Analysis of
      single tSNPs, corrected for multiple comparisons (p < 0.00485), identified allele
      +1086A to be associated with CAD (p = 0.0034). Suggestive allelic and significant
      genotypic associations were found for -631AA (odds ratio [OR] = 3.95, p = 0.004
      vs. CC) and +2389GA (OR = 1.21, p = 0.003 vs. GG). Haplotype analysis by linkage
      disequilibrium (LD) group revealed a CAD association for LD group B (p = 0.0025
      across T+1086A, C+878T, C+408T) and near significance for LD group A (p = 0.013
      across C-631A, MspI, G+2389A). A weak protective trend for TaqIB was eliminated
      by adjustment for other tSNPs, and haplotype analyses suggested that TaqIB was
      simply a marker for other tSNPs or haplotypes. No tSNP or haplotype associations
      with MI were found. CONCLUSIONS: Multiple, less common SNPs and haplotype
      variants underlie CETP-related CAD risk, for which the common TaqIB variant is
      simply a poor marker. The occurrence of risk-related variants on separate
      haplotypes suggests genetic-risk complexity and allelic heterogeneity. (Database
      Registry of the Intermountain Heart Collaborative Study;
      http://clinicaltrials.gov/ct/show/NCT00406185?order=1; NCT00406185).

PMID- 17512364
TI  - The year in clinical cardiac electrophysiology.

PMID- 17512365
TI  - Value of multislice computed tomography coronary angiography in suspected
      coronary artery disease.

PMID- 17512367
TI  - Taking on the opposition, male circumcision and other themes.

PMID- 17512368
TI  - Male circumcision for HIV prevention: the research evidence and some critical
      responses.
AB  - Three randomised clinical trials, in South Africa, Uganda and Kenya, have shown a
      substantial reduction in female-to-male transmission of HIV to men who had been
      circumcised as compared to men who had not, during a follow-up period of up to 24
      months. The question of what to do with this evidence is currently being debated
      around the world. WHO and UNAIDS took the lead by developing technical, policy
      and programmatic guidance following a series of consultations with a range of
      stakeholders in the field, using the research evidence as the basis. Consensus on
      many aspects of this matter is far from being achieved, however. Many questions
      and different points of view are emerging--clinical, public health, sociological,
      anthropological and cultural; in relation to priority setting in HIV prevention
      and delivery of health services; and in relation to sexuality, ethics, gender and
      rights. On 28 March 2007, WHO and UNAIDS published a set of conclusions and
      recommendations regarding the research implications for HIV policy and
      programming. The introduction and excerpts from these follow below. They are, in
      turn, followed by a roundtable of nine papers which contain a range of critical
      thinking and analysis of these issues. Male circumcision is generating debate
      across the globe. This can only be a good thing, as it is a complex matter and
      far more than a straightforward public health intervention. We hope these papers
      will help to inform that debate.

PMID- 17512369
TI  - Male circumcision for HIV prevention: research implications for policy and
      programming. WHO/UNAIDS technical consultation, 6-8 March 2007. Conclusions and
      recommendations (excerpts).

PMID- 17512370
TI  - "Just a snip"?: a social history of male circumcision.

PMID- 17512371
TI  - "You can also cut my finger!": social construction of male circumcision in West
      Africa, a case study of Senegal and Guinea-Bissau.

PMID- 17512372
TI  - Male circumcision and HIV prevention: is there really enough of the right kind of
      evidence?

PMID- 17512373
TI  - Male circumcision for HIV prevention: perspectives on gender and sexuality.

PMID- 17512374
TI  - Male circumcision, in so many words...

PMID- 17512375
TI  - The new evidence on male circumcision: an Indian perspective.

PMID- 17512376
TI  - Delivery of male circumcision services: "Festina lente".

PMID- 17512377
TI  - Male circumcision: implications for women as sexual partners and parents.

PMID- 17512378
TI  - Sexually transmitted infection management, safer sex promotion and voluntary HIV
      counselling and testing in the male circumcision trial, Rakai, Uganda.

PMID- 17512379
TI  - Abortion and Islam: policies and practice in the Middle East and North Africa.
AB  - This paper provides an overview of legal, religious, medical and social factors
      that serve to support or hinder women's access to safe abortion services in the
      21 predominantly Muslim countries of the Middle East and North Africa (MENA)
      region, where one in ten pregnancies ends in abortion. Reform efforts, including
      progressive interpretations of Islam, have resulted in laws allowing for early
      abortion on request in two countries; six others permit abortion on health
      grounds and three more also allow abortion in cases of rape or fetal impairment.
      However, medical and social factors limit access to safe abortion services in all
      but Turkey and Tunisia. To address this situation, efforts are increasing in a
      few countries to introduce post-abortion care, document the magnitude of unsafe
      abortion and understand women's experience of unplanned pregnancy. Religious
      fatawa have been issued allowing abortions in certain circumstances. An
      understanding of variations in Muslim beliefs and practices, and the interplay
      between politics, religion, history and reproductive rights is key to
      understanding abortion in different Muslim societies. More needs to be done to
      build on efforts to increase women's rights, engage community leaders, support
      progressive religious leaders and government officials and promote advocacy among
      health professionals.

PMID- 17512380
TI  - Abortion in democratic Spain: the parliamentary political agenda 1979-2004.
AB  - Since Spain's transition to democracy, abortion has been a public policy issue
      both inside and outside parliament. This paper describes the history of abortion
      law reform in Spain from 1979 to 2004 and analyses the discourse on abortion of
      members of the Spanish parliament by sex and political allegiance. The analysis
      is based on a retrospective study of the frequency of legislative initiatives and
      the prevalence of different arguments and positions in debates on abortion found
      through a systematic search of the parliamentary database. Little time was given
      to abortion in the parliamentary agenda compared to other women's issues such as
      violence against women. There were 229 bills and other parliamentary initiatives
      in that period, 60% initiated and led by pro-choice women. 143 female and 72 male
      parliamentarians took part in the debates. The inclusion of socio-economic
      grounds for legal abortion (64%), and making abortion on request legal in the
      first 12 weeks of pregnancy (60%) were the most frequent forms of law reform
      proposed, based most often on pro-women's rights arguments. Male and female
      members of anti-choice parties and most male members of other parties argued for
      fetal rights. Pro-choice parties tabled more bills than anti-choice parties but
      till now all reforms proposed since 1985 have been voted down.

PMID- 17512381
TI  - Knowledge and perception of abortion and the abortion law in Trinidad and Tobago.
AB  - As for most of its Caribbean neighbours, Trinidad and Tobago's leading cause of
      maternal morbidity is unsafe abortion. Yet activism to introduce public policy
      and legislation that effectively address this aspect of women's reproductive
      rights and health has been met with public outcry. With almost hysterical
      opposition coming from certain religious quarters, there is the unsubstantiated
      impression that Trinidadians are overwhelmingly opposed to abortion law reform. A
      national survey was therefore carried out of people's knowledge and views on the
      current abortion law in Trinidad and Tobago. The survey found that although
      almost half of respondents had an unfavourable perception of abortion, more than
      half of them were in favour of broadening the legal grounds for accessing
      terminations. Incest, rape and danger to a woman's life were cited as the most
      significant circumstances under which abortions should be permitted. The vast
      majority of respondents agreed that voting on abortion law reform by members of
      the legislature should not be based on personal beliefs. The findings demonstrate
      that there is not the degree of opposition to abortion law reform that is widely
      assumed. On the other hand, given the wide variance of views and perceptions, we
      argue that public health concerns and human rights should always trump public
      opinion.

PMID- 17512382
TI  - Sexual and reproductive health needs of sex workers: two feminist projects in
      Brazil.
AB  - The sexual and reproductive health needs of sex workers have been neglected both
      in research and public health interventions, which have almost exclusively
      focused on STI/HIV prevention. Among the reasons for this are the condemnation,
      stigma and ambiguous legal status of sex work. This paper describes work carried
      out by two feminist NGOs in Brazil, Mulher e Saude (MUSA) in Belo Horizonte and
      Coletivo Feminista Sexualidade e Saude in Sao Paulo, to promote sexual and
      reproductive health for sex workers. MUSA's project "In the Battle for Health",
      was begun in 1992; sex workers were trained as peer educators and workshops were
      offered on self-care for sex workers and their clients. In Sao Paulo, the
      Coletivo project "Get Friendly with Her", begun in 2002, offers clinic
      consultations and self-care workshops on sexuality, contraception, STI/HIV
      prevention and self-examination. Health care needs during menstruation and
      unhealthy vaginal practices led to promotion of the diaphragm as a contraceptive,
      for prevention of reproductive tract infection and to catch menstrual blood.
      Meeting the sexual and reproductive health needs of sex workers depends on the
      promotion of their human rights, access to health care without discrimination,
      and attention to psychosocial health issues, alcohol and drug abuse, and violence
      from clients, partners, pimps and police.

PMID- 17512383
TI  - Building coalitions to support women's health and rights in the United States:
      South Carolina and Florida.
AB  - There is a health care crisis in the United States and women, particularly low
      income women and women of colour, are paying the price. The politicisation of
      pregnancy, sexuality and women's reproductive rights has created a uniquely
      contradictory situation in many states. Policymakers are working to control
      women's reproductive choices and sexuality, and restricting sex education, but
      doing little to address the overall lack of access to quality reproductive health
      care. This article describes a new reproductive rights advocacy model that was
      implemented starting in 2003 in two US states, South Carolina and Florida. In
      depth research on the status of reproductive health and rights in each state,
      analysed by race, economic status, county and state policy initiatives relevant
      to women's health, showed that in both states access to contraception and
      abortion, cervical and breast cancer screening and treatment, HIV/AIDS-related
      care and pregnancy care were poor, with African American and Hispanic women
      faring even worse than white women. Implementing the advocacy model involved
      identifying and bringing together a diverse set of health care professionals,
      academics and activists who formed coalitions and are now working together and
      developing advocacy strategies in support of policies to improve access to
      reproductive health care and protect reproductive rights in both states.

PMID- 17512384
TI  - Emergency contraception under attack in Latin America: response of the medical
      establishment and civil society.
AB  - The concept that it is possible to prevent a pregnancy after coitus is not new,
      but has gained prominence over the last 10-15 years. It provides a second chance
      to women who do not want to get pregnant and who, voluntarily or not, have had
      unprotected intercourse. Emergency contraception has been under strong attack by
      the Catholic church and anti-choice organisations in Latin America, who claim
      that the interference with implantation of the fertilised ovum is equivalent to
      an early abortion. The accumulation of evidence, however, is that the mechanism
      of action of emergency contraception is to prevent ovulation and that it does not
      interfere with implantation. This has been ignored by the anti-choice movement.
      The pattern of opposition to emergency contraception has been the same all over
      the Latin America region. The medical establishment and civil society, including
      the International Consortium for Emergency Contraception, have played a key role
      in defending access to emergency contraception throughout the region. A positive
      consequence of the public opposition of the Catholic church is that the concept
      and the method have become better known, and emergency contraception has become
      widely used. The cases of Peru, Brazil and Chile are described as examples.

PMID- 17512385
TI  - Emergency contraception in Peru: shifting government and donor policies and
      influences.
AB  - Inclusion of emergency contraception in national family planning programmes is
      consistent with international agreements that countries should strive to ensure
      access to a wide range of contraceptive methods and promote voluntary, informed
      choice. Yet in 2005, USAID/Peru requested that its NGO grantees in Peru take a
      "neutral" position on emergency contraception in activities or materials that
      involve its funds. For many decades, donor countries have viewed conservative
      religious forces in low-income countries as an obstacle to expanding family
      planning programmes. Today, however, far-right organisations in the United States
      are having an unprecedented influence on US public policy, including in countries
      such as Peru. This article analyses shifts in USAID/Peru's policy on emergency
      contraception in Peru since 1992. In Peru today, there is widespread official and
      public support for making emergency contraception available. Given USAID's long
      support for family planning internationally and in Peru, the current policy
      appears to be the result of attacks by US far-right organisations carried out in
      synergy with sympathetic US public officials and anti-choice Peruvian allies.

PMID- 17512386
TI  - Legislating against sexual violence in Kenya: an Interview with the Hon. Njoki
      Ndungu.
AB  - Sexual violence is rampant in Kenya and the law was not adequately dealing with
      it. This is an interview by the Association for Women's Rights in Development
      (AWID) with the Hon. Njoki Ndungu, a Member of the Kenyan Parliament. It is about
      the history of the development and passage of the Sexual Offences Act, which came
      into law in Kenya in July 2006. The law contains 14 offences; it has created
      minimum sentences and criminalised sexual harassment. The media and radio
      stations had a big role in getting everyone talking about the issues, and support
      was widespread. Women's organisations and women's rights advocates played an
      important role, including lobbying members of Parliament, but there were some
      disagreements about tactics, such as whether demonstrations to support the bill
      were a good idea or not. The opposition claimed the bill would encourage women to
      make false rape allegations. As a way to discredit it, they also falsely claimed
      that it would legalise same-sex relations and abortion. Work is now in progress
      on a curriculum for training the police, public administration and judiciary on
      the new Act and its application, as well as a public awareness programme aimed at
      encouraging people to report incidents of sexual violence.

PMID- 17512387
TI  - The commodification of obstetric ultrasound scanning in Hanoi, Viet Nam.
AB  - Growing numbers of pregnant women across the world now routinely have ultrasound
      scans as part of antenatal care, including in low-income countries. This article
      presents the findings of anthropological research on the use of obstetric
      ultrasonography in routine antenatal care in Hanoi, Viet Nam. The findings come
      from observation, a survey and interviews with women seeking ultrasound scans at
      a main maternity hospital and interviews with doctors providing ultrasound there.
      We found a dramatic overuse of ultrasound scanning; the 400 women surveyed had
      had an average of 6.6 scans and 8.3 antenatal visits during pregnancy, while one
      fifth had had ten scans or more. Doctors considered obstetric ultrasound an
      indispensable part of modern antenatal care. For two-thirds of the women, the
      main reason for frequent scans was reassurance of normal fetal development.
      However, the women often also said their doctor had recommended the scans. This
      overuse must be seen in the context of growing commercialisation in the
      Vietnamese health care system, where ultrasound provides an important source of
      revenue for both private and public providers. There is an urgent need in Viet
      Nam for policy and practice guidelines on the appropriate use of ultrasonography
      in pregnancy and how best to combine it with essential antenatal care, and
      information dissemination to women.

PMID- 17512388
TI  - Situation analysis of quality of abortion care in the main maternity hospital in
      Hai Phong, Viet Nam.
AB  - Six months after a Comprehensive Abortion Care project was implemented in Phu-San
      Hospital, the main maternity hospital in Hai Phong, northern Viet Nam, a study of
      quality of abortion services was carried out. The study explored the interaction
      between providers and women seeking abortion and how cultural values influenced
      quality of care. A quantitative and qualitative approach was employed: a three
      part structured survey with 748 women before and after they had an abortion, 20
      in-depth interviews with women just after abortion, seven informal interviews
      with health care staff and 100 participant observations. Both the women and the
      staff equated quality of care mainly with improved technical performance of
      abortion. Insufficient knowledge and skills had a negative impact on provision of
      information and good quality counselling in relation to understanding and uptake
      of contraception, treating reproductive tract infection and preventing post
      abortion infection. To further improve abortion care in hospitals such as Phu
      San, training programmes are needed that integrate counselling and clinical
      skills and address the cultural factors that hinder health staff and women from
      interacting in an equitable manner. A supportive supervisory system that holds
      health staff accountable for conducting high quality information and counselling
      sessions should also be established.

PMID- 17512389
TI  - Are monthly menstrual periods optional?: A European perspective.
AB  - Throughout human history, women have experienced menstruation, whether as a
      positive or a negative experience. The timing of periods was impossible to
      predict or to change. For the first time in human history, hormonal contraception
      has changed women's options, and the use of oestrogen-progestogen contraception
      can control whether and when a woman has a period. This article argues, on the
      basis of recent studies in the Netherlands, Germany, France and Italy, that a
      growing number of Western European women want no periods or would like to have a
      longer interval between periods. And why not!

PMID- 17512390
TI  - Targeting access to reproductive health: giving contraception more prominence and
      using indicators to monitor progress.
AB  - Unmet need for contraception represents a major failure in the provision of
      reproductive health services and reflects the extent of access to services for
      spacing and limiting births, which are also affected by personal, partner,
      community and health system factors. In the context of the Millennium Development
      Goals, family planning has been given insufficient attention compared to maternal
      health and the control of sexually transmitted infections. As this omission is
      being redressed, efforts should be directed towards ensuring that an indicator of
      unmet need is used as a measure of access to services. The availability of data
      on unmet need must also be increased to enable national comparisons and
      facilitate resource mobilisation. Unmet need is a vital component in monitoring
      the proportion of women able to space and limit births. Unmet need for
      contraception is a measure conditioned by people's preferences and choices and
      therefore firmly introduces a rights perspective into development discourse and
      serves as an important instrument to improve the sensitivity of policy dialogue.
      The new reproductive health target and the opportunity it offers to give
      appropriate attention to unmet need for contraception will allow the entry of
      other considerations vital to ensuring universal access to reproductive health.

PMID- 17512391
TI  - Use of unsafe condoms and unsafe use of good condoms.

PMID- 17512392
TI  - Back to the future: The Madrid Declaration and the European Heart Health Charter.

PMID- 17512393
TI  - The challenge of changing practice and improving care.

PMID- 17512394
TI  - Returning home.
AB  - Returning to one's home country after many years abroad is a life-changing
      decision that brings with it many challenges, but at the same time, many rewards.

PMID- 17512395
TI  - Gap junctions provide new links in left-right patterning.
AB  - Gap junctions are increasingly recognized as key regulators of embryonic
      development, nervous system function, and neoplasia. Chuang et al. (2007) now
      show that developing neural circuits use communication through gap junctions to
      establish left-right asymmetry in the central nervous system of the worm
      Caenorhabditis elegans, revealing that nematodes share a mechanism for left-right
      asymmetry in common with vertebrates.

PMID- 17512396
TI  - Inositol pyrophosphates get the vip1 treatment.
AB  - Inositol pyrophosphates are unique signaling molecules implicated in the
      regulation of diverse cellular processes. Two new studies by Mulugu et al. (2007)
      and Lee et al. (2007) extend the biological and metabolic diversity of this class
      of molecules. They identify yeast Vip1 as a new inositol pyrophosphate synthase
      and show that the products of Vip1 activity regulate a cyclin/cyclin-dependent
      kinase complex.

PMID- 17512397
TI  - Guiding ligands to nuclear receptors.
AB  - Retinoic acid-the active metabolite of vitamin A-influences biological processes
      by activating the retinoic acid receptor (RAR). In this issue, Schug et al.
      (2007) demonstrate that retinoic acid also activates the peroxisome proliferator
      activated receptor beta/delta (PPARbeta/delta). Remarkably, retinoic acid
      signaling through RAR or PPARbeta/delta-which depends on cytoplasmic retinoic
      acid transporters-commits the cell to opposite fates, apoptosis or survival,
      respectively.

PMID- 17512398
TI  - DegrAAAded into silence.
AB  - In fission yeast, RNA interference (RNAi)-dependent heterochromatin formation
      silences transgenes inserted at centromeres. In this issue, Buhler et al. (2007)
      demonstrate that the RNAi machinery directly targets transgene transcripts.
      Furthermore, they link transgene silencing to a protein complex resembling the
      TRAMP complex of budding yeast, which promotes transcript degradation via the
      exosome. Thus, RNAi-independent transcript degradation may also contribute to
      heterochromatin gene silencing.

PMID- 17512399
TI  - Immunological synapses: breaking up may be good to do.
AB  - Activated T cells form stable immunological synapses with antigen-presenting
      cells whereas naive T cells initially engage in more transient interactions. Sims
      et al. (2007) demonstrate that these transient interactions are due to the kinase
      PKCtheta, which serves to destabilize the synapse thereby permitting T cells to
      migrate elsewhere. They also show that re-establishment of a synapse involves the
      actin regulator WASp.

PMID- 17512400
TI  - "Wunder" F-BAR domains: going from pits to vesicles.
AB  - Clathrin-mediated endocytosis is a key mechanism by which cells take up
      extracellular cargo. In this issue, Shimada et al. (2007) reveal the mode of
      action of the F-BAR domain, which deepens the initial membrane pit that forms
      during clathrin-mediated endocytosis.

PMID- 17512401
TI  - Proteasomes: machines for all reasons.
AB  - Emerging data reveal that besides degrading proteins tagged with ubiquitin, the
      proteasome plays a more varied and decisive role in cellular regulation than
      previously imagined. In this issue, Hanna et al. (2007) expand our view of the
      proteasome by showing that under certain conditions, proteasome composition can
      be altered to control ubiquitin homeostasis.

PMID- 17512402
TI  - PCNA, the maestro of the replication fork.
AB  - Inheritance requires genome duplication, reproduction of chromatin and its
      epigenetic information, mechanisms to ensure genome integrity, and faithful
      transmission of the information to progeny. Proliferating cell nuclear antigen
      (PCNA)-a cofactor of DNA polymerases that encircles DNA-orchestrates several of
      these functions by recruiting crucial players to the replication fork.
      Remarkably, many factors that are involved in replication-linked processes
      interact with a particular face of PCNA and through the same interaction domain,
      indicating that these interactions do not occur simultaneously during
      replication. Switching of PCNA partners may be triggered by affinity-driven
      competition, phosphorylation, proteolysis, and modification of PCNA by ubiquitin
      and SUMO.

PMID- 17512403
TI  - 5'-to-3' exoribonuclease activity in bacteria: role of RNase J1 in rRNA
      maturation and 5' stability of mRNA.
AB  - Although the primary mechanism of eukaryotic messenger RNA decay is
      exoribonucleolytic degradation in the 5'-to-3' orientation, it has been widely
      accepted that Bacteria can only degrade RNAs with the opposite polarity, i.e. 3'
      to 5'. Here we show that maturation of the 5' side of Bacillus subtilis 16S
      ribosomal RNA occurs via a 5'-to-3' exonucleolytic pathway, catalyzed by the
      widely distributed essential ribonuclease RNase J1. The presence of a 5'-to-3'
      exoribonuclease activity in B. subtilis suggested an explanation for the
      phenomenon whereby mRNAs in this organism are stabilized for great distances
      downstream of "roadblocks" such as stalled ribosomes or stable secondary
      structures, whereas upstream sequences are never detected. We show that a 30S
      ribosomal subunit bound to a Shine Dalgarno-like element (Stab-SD) in the cryIIIA
      mRNA blocks exonucleolytic progression of RNase J1, accounting for the
      stabilizing effect of this element in vivo.

PMID- 17512404
TI  - Perinucleolar targeting of the inactive X during S phase: evidence for a role in
      the maintenance of silencing.
AB  - In mammalian females, two X chromosomes are epigenetically distinguished as
      active and inactive chromosomes to balance X-linked gene dosages between males
      and females. How the Xs are maintained differently in the same nucleus remains
      unknown. Here, we demonstrate that the inactive X (Xi) is targeted to a distinct
      nuclear compartment following pairing with its homologous partner. During mid-to
      late S phase, 80%-90% of Xi contact the nucleolus and reside within a Snf2h
      enriched ring. Autosomes carrying ectopic X-inactivation center sequences are
      also targeted to the perinucleolar compartment. Deleting Xist results in a loss
      of nucleolar association and an inability to maintain Xi heterochromatin, leading
      to Xi reactivation at the single gene level. We propose that the Xi must
      continuously visit the perinucleolar compartment to maintain its epigenetic
      state. These data raise a mechanism by which chromatin states can be replicated
      by spatial and temporal separation in the nucleus.

PMID- 17512405
TI  - RNAi-dependent and -independent RNA turnover mechanisms contribute to
      heterochromatic gene silencing.
AB  - In fission yeast, the RNAi pathway is required for heterochromatin-dependent
      silencing of transgene insertions at centromeric repeats and acts together with
      other pathways to silence transgenes at the silent mating-type locus. Here, we
      show that transgene transcripts at centromeric repeats are processed into siRNAs
      and are therefore direct targets of RNAi. Furthermore, we show that Cid14, a
      member of the Trf4/5 family of poly(A) polymerases, has poly(A) polymerase
      activity that is required for heterochromatic gene silencing. Surprisingly, while
      siRNA levels in cid14Delta cells are dramatically reduced, the structural
      integrity of heterochromatin appears to be preserved. Cid14 resides in a complex
      similar to the TRAMP complex found in budding yeast, which is part of a nuclear
      surveillance mechanism that degrades aberrant transcripts. Our findings indicate
      that polyadenylation by a TRAMP-like complex contributes to robust silencing of
      heterochromatic genes in fission yeast via the recruitment of the exosome and/or
      the RNAi machinery.

PMID- 17512407
TI  - Structural basis for the inhibition of tyrosine kinase activity of ZAP-70.
AB  - ZAP-70, a cytoplasmic tyrosine kinase required for T cell antigen receptor
      signaling, is controlled by a regulatory segment that includes a tandem SH2 unit
      responsible for binding to immunoreceptor tyrosine-based activation motifs
      (ITAMs). The crystal structure of autoinhibited ZAP-70 reveals that the inactive
      kinase domain adopts a conformation similar to that of cyclin-dependent kinases
      and Src kinases. The autoinhibitory mechanism of ZAP-70 is, however, distinct and
      involves interactions between the regulatory segment and the hinge region of the
      kinase domain that reduce its flexibility. Two tyrosine residues in the SH2
      kinase linker that activate ZAP-70 when phosphorylated are involved in aromatic
      aromatic interactions that connect the linker to the kinase domain. These
      interactions are inconsistent with ITAM binding, suggesting that destabilization
      of this autoinhibited ZAP-70 conformation is the first step in kinase activation.

PMID- 17512406
TI  - Opposing effects of retinoic acid on cell growth result from alternate activation
      of two different nuclear receptors.
AB  - Transcriptional activation of the nuclear receptor RAR by retinoic acid (RA)
      often leads to inhibition of cell growth. However, in some tissues, RA promotes
      cell survival and hyperplasia, activities that are unlikely to be mediated by
      RAR. Here, we show that, in addition to functioning through RAR, RA activates the
      "orphan" nuclear receptor PPARbeta/delta, which, in turn, induces the expression
      of prosurvival genes. Partitioning of RA between the two receptors is regulated
      by the intracellular lipid binding proteins CRABP-II and FABP5. These proteins
      specifically deliver RA from the cytosol to nuclear RAR and PPARbeta/delta,
      respectively, thereby selectively enhancing the transcriptional activity of their
      cognate receptors. Consequently, RA functions through RAR and is a proapoptotic
      agent in cells with high CRABP-II/FABP5 ratio, but it signals through
      PPARbeta/delta and promotes survival in cells that highly express FABP5. Opposing
      effects of RA on cell growth thus emanate from alternate activation of two
      different nuclear receptors.

PMID- 17512408
TI  - A ubiquitin stress response induces altered proteasome composition.
AB  - Ubiquitin-dependent protein degradation is essential for cells to survive many
      environmental stresses. Thus, it may be necessary to buffer ubiquitin and
      proteasome pools against fluctuation. Proteasome levels are tightly regulated,
      and proteasome deficiency stimulates a stress response. Here we report a novel
      pathway of cellular response to ubiquitin depletion. Unlike proteasome stress,
      ubiquitin stress does not upregulate proteasome abundance. Instead, ubiquitin
      stress alters proteasome composition. The proteasome-associated deubiquitinating
      enzyme Ubp6, which spares ubiquitin from proteasomal degradation, is induced by
      ubiquitin deficiency. This enhances loading of proteasomes with Ubp6, thereby
      altering proteasome function. A catalytically inactive mutant of Ubp6 fails to
      recycle ubiquitin and also inhibits proteasome function directly, thus inducing
      both ubiquitin stress and proteasome stress. These results show that homeostatic
      control of the ubiquitin-proteasome pathway can be achieved through signal
      dependent, subunit-specific regulation of the proteasome, and indicate a dual
      role of Ubp6 in regulating ubiquitin levels and proteasome function.

PMID- 17512409
TI  - Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane
      invagination in endocytosis.
AB  - Pombe Cdc15 homology (PCH) proteins play an important role in a variety of actin
      based processes, including clathrin-mediated endocytosis (CME). The defining
      feature of the PCH proteins is an evolutionarily conserved EFC/F-BAR domain for
      membrane association and tubulation. In the present study, we solved the crystal
      structures of the EFC domains of human FBP17 and CIP4. The structures revealed a
      gently curved helical-bundle dimer of approximately 220 A in length, which forms
      filaments through end-to-end interactions in the crystals. The curved EFC dimer
      fits a tubular membrane with an approximately 600 A diameter. We subsequently
      proposed a model in which the curved EFC filament drives tubulation. In fact,
      striation of tubular membranes was observed by phase-contrast cryo-transmission
      electron microscopy, and mutations that impaired filament formation also impaired
      membrane tubulation and cell membrane invagination. Furthermore, FBP17 is
      recruited to clathrin-coated pits in the late stage of CME, indicating its
      physiological role.

PMID- 17512410
TI  - Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the
      immunological synapse.
AB  - The immunological synapse (IS) is a junction between the T cell and antigen
      presenting cell and is composed of supramolecular activation clusters (SMACs). No
      studies have been published on naive T cell IS dynamics. Here, we find that IS
      formation during antigen recognition comprises cycles of stable IS formation and
      autonomous naive T cell migration. The migration phase is driven by PKCtheta,
      which is localized to the F-actin-dependent peripheral (p)SMAC. PKCtheta(-/-) T
      cells formed hyperstable IS in vitro and in vivo and, like WT cells, displayed
      fast oscillations in the distal SMAC, but they showed reduced slow oscillations
      in pSMAC integrity. IS reformation is driven by the Wiscott Aldrich Syndrome
      protein (WASp). WASp(-/-) T cells displayed normal IS formation but were unable
      to reform IS after migration unless PKCtheta was inhibited. Thus, opposing
      effects of PKCtheta and WASp control IS stability through pSMAC symmetry breaking
      and reformation.

PMID- 17512411
TI  - An innexin-dependent cell network establishes left-right neuronal asymmetry in C.
      elegans.
AB  - Gap junctions are widespread in immature neuronal circuits, but their functional
      significance is poorly understood. We show here that a transient network formed
      by the innexin gap-junction protein NSY-5 coordinates left-right asymmetry in the
      developing nervous system of Caenorhabditis elegans. nsy-5 is required for the
      left and right AWC olfactory neurons to establish stochastic, asymmetric patterns
      of gene expression during embryogenesis. nsy-5-dependent gap junctions in the
      embryo transiently connect the AWC cell bodies with those of numerous other
      neurons. Both AWCs and several other classes of nsy-5-expressing neurons
      participate in signaling that coordinates left-right AWC asymmetry. The right AWC
      can respond to nsy-5 directly, but the left AWC requires nsy-5 function in
      multiple cells of the network. NSY-5 forms hemichannels and intercellular gap
      junction channels in Xenopus oocytes, consistent with a combination of cell
      intrinsic and network functions. These results provide insight into gap-junction
      activity in developing circuits.

PMID- 17512412
TI  - Nuclear translocation of CAM-associated protein activates transcription for long
      term facilitation in Aplysia.
AB  - Repeated pulses of serotonin (5-HT) induce long-term facilitation (LTF) of the
      synapses between sensory and motor neurons of the gill-withdrawal reflex in
      Aplysia. To explore how apCAM downregulation at the plasma membrane and CREB
      mediated transcription in the nucleus, both of which are required for the
      formation of LTF, might relate to each other, we cloned an apCAM-associated
      protein (CAMAP) by yeast two-hybrid screening. We found that 5-HT signaling at
      the synapse activates PKA which in turn phosphorylates CAMAP to induce the
      dissociation of CAMAP from apCAM and the subsequent translocation of CAMAP into
      the nucleus of sensory neurons. In the nucleus, CAMAP acts as a transcriptional
      coactivator for CREB1 and is essential for the activation of ApC/EBP required for
      the initiation of LTF. Combined, our data suggest that CAMAP is a retrograde
      signaling component that translocates from activated synapses to the nucleus
      during synapse-specific LTF.

PMID- 17512413
TI  - Theoretical analysis of epigenetic cell memory by nucleosome modification.
AB  - Chromosomal regions can adopt stable and heritable alternative states resulting
      in bistable gene expression without changes to the DNA sequence. Such epigenetic
      control is often associated with alternative covalent modifications of histones.
      The stability and heritability of the states are thought to involve positive
      feedback where modified nucleosomes recruit enzymes that similarly modify nearby
      nucleosomes. We developed a simplified stochastic model for dynamic nucleosome
      modification based on the silent mating-type region of the yeast
      Schizosaccharomyces pombe. We show that the mechanism can give strong bistability
      that is resistant both to high noise due to random gain or loss of nucleosome
      modifications and to random partitioning upon DNA replication. However, robust
      bistability required: (1) cooperativity, the activity of more than one modified
      nucleosome, in the modification reactions and (2) that nucleosomes occasionally
      stimulate modification beyond their neighbor nucleosomes, arguing against a
      simple continuous spreading of nucleosome modification.

PMID- 17512414
TI  - High-resolution profiling of histone methylations in the human genome.
AB  - Histone modifications are implicated in influencing gene expression. We have
      generated high-resolution maps for the genome-wide distribution of 20 histone
      lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase
      II, and the insulator binding protein CTCF across the human genome using the
      Solexa 1G sequencing technology. Typical patterns of histone methylations
      exhibited at promoters, insulators, enhancers, and transcribed regions are
      identified. The monomethylations of H3K27, H3K9, H4K20, H3K79, and H2BK5 are all
      linked to gene activation, whereas trimethylations of H3K27, H3K9, and H3K79 are
      linked to repression. H2A.Z associates with functional regulatory elements, and
      CTCF marks boundaries of histone methylation domains. Chromosome banding patterns
      are correlated with unique patterns of histone modifications. Chromosome
      breakpoints detected in T cell cancers frequently reside in chromatin regions
      associated with H3K4 methylations. Our data provide new insights into the
      function of histone methylation and chromatin organization in genome function.

PMID- 17512415
TI  - Snapshot: genetic mouse models of cancer.

PMID- 17512417
TI  - Use of device diagnostics in the outpatient management of heart failure.
AB  - Implantable cardiac devices now go far beyond the functionality of early
      pacemakers and defibrillators. They provide us with an unprecedented amount of
      information about the day-to-day status of our patients with heart failure,
      providing insight into the complex clinical picture of these patients. More
      advanced technology can be seen on the horizon, and the development of strategies
      to incorporate this information into our clinics is needed. Traditionally,
      information from devices has only been accessed by the physicians implanting the
      device. However, heart failure physicians and their patients can benefit from the
      information now available and from having ways to access and use the data. This
      article focuses on the successful integration of device-based data into patient
      care in the outpatient clinical setting.

PMID- 17512418
TI  - Integrating device-based monitoring into clinical practice: insights from a large
      heart failure clinic.
AB  - Heart failure is a difficult and costly disease to manage in part because the
      symptoms may be protean, the physical findings obscure, and the laboratory
      assessments unreliable. New implanted physiologic monitors may simplify the care
      of patients with heart failure, if they can be incorporated into routine clinical
      practice. Cardiac resynchronization therapy/defibrillators and implantable
      cardioverter defibrillators with continuous intrathoracic impedance monitoring
      capabilities (OptiVol fluid status monitoring; Medtronic, Inc., Minneapolis, MN)
      have recently been introduced and may provide an early warning of thoracic fluid
      retention. However, patients who have devices with this diagnostic capability
      must be identified, and the device-based information must be accessed
      systematically, if it is to be used in the disease management process. Ancillary
      information, such as the Heart Failure Management Report that is generated from
      data stored in Medtronic devices, may facilitate recognition of disease
      mechanisms associated with decompensation. The predictive value of continuous
      intrathoracic impedance monitoring with an implantable device is still unknown.
      Thus, therapeutic decisions should be made in conjunction with a clinical
      assessment. Physicians and other healthcare providers will need to become
      familiar with these devices so they can appreciate their advantages and
      limitations.

PMID- 17512419
TI  - Device monitoring of intrathoracic impedance: clinical observations from a
      patient registry.
AB  - A distinct advantage of implantable device diagnostics is that the data may be
      made available on a continuous basis, rather than at sporadic intervals
      associated with clinical testing. Recently, intrathoracic impedance monitoring
      has also become available in some implantable devices as an index of congestion
      and thoracic fluid accumulation secondary to decompensated heart failure. Despite
      the potential advantages, new advances in implantable device diagnostic
      technology also pose important questions regarding their clinical application. To
      examine these questions and to generate hypotheses, the relation between daily
      intrathoracic impedance measurements and other physical measurements or
      comorbidities was studied. A retrospective review was performed of 25 patients
      who previously underwent implantation of a cardiac resynchronization
      therapy/defibrillator device with the capability to continuously monitor
      intrathoracic impedance. This limited scope analysis demonstrated that daily
      measurement of intrathoracic impedances might reveal the intrinsic relations
      between heart failure decompensation and the onset of atrial and ventricular
      arrhythmias. Abnormal patterns of intrathoracic impedance that has increased and
      plateaued after implant may indicate worsening heart failure. The severity of
      congestive heart failure at the time of interrogation may correlate with device
      based impedance measurements. Weight, sex, and body index may have a limited
      impact on impedance, and the lowest impedances may be seen in older patients.
      Patients with severe pulmonary disease may present with unique daily impedance
      profiles. Finally, daily impedance may have unpredictable relations with other
      clinical markers of heart failure. In summary, intrathoracic impedance represents
      a clinically useful diagnostic tool that can increase our understanding of a
      dynamic disease state on an individual patient basis.

PMID- 17512420
TI  - Use of device diagnostics as an educational tool to improve patient adherence.
AB  - Implantable cardiac devices are increasingly being used to treat heart failure
      and may provide an opportunity to more effectively monitor a patient's clinical
      status and prevent hospitalization by detecting subclinical congestion before
      progression to acute decompensated heart failure. This article reviews the use of
      device diagnostics in clinical practice and discusses their utility as tools in
      heart failure disease management, with a focus on the use of a new intrathoracic
      impedance diagnostic as an educational tool to improve patient adherence.

PMID- 17512421
TI  - Fundamentals of intrathoracic impedance monitoring in heart failure.
AB  - The primary objective of the first-generation implantable cardiac pacemakers was
      to provide critical heart rate support, but these devices did not have any
      diagnostic capabilities. In the intervening decades, the number, type, and
      complexity of implantable devices has greatly expanded. Today, implantable
      devices not only provide heart rate support but they also provide protection from
      sudden cardiac death with implantable cardioverter defibrillators (ICDs) and
      reduce symptoms and increase survival with cardiac resynchronization therapy
      (CRT). Furthermore, information on physiologic variables has been collected in
      patients with implanted devices for the purpose of providing sophisticated closed
      loop optimization of their pacing and defibrillation algorithms. Thoracic fluid
      status monitoring via intrathoracic impedance is the newest device-based
      diagnostic capability. For those patients with heart failure who are already
      targeted to receive an ICD or CRT with defibrillator implant, the ability to
      monitor fluid status can provide additional insight into the difficult problem of
      evaluating and managing these patients. This article reviews the basics of
      measuring intrathoracic impedance via OptiVol fluid status monitoring (Medtronic,
      Inc., Minneapolis, MN), as well as clinical results regarding the utility of
      evaluating OptiVol intrathoracic impedance data trends.

PMID- 17512422
TI  - Key lessons from cases worldwide.
AB  - Since OptiVol fluid status monitoring (Medtronic, Inc., Minneapolis, MN) was
      released to the market in 2004, the manufacturer has been working together with
      clinicians to better understand the operation and utility of OptiVol in a
      clinical setting. This has been done through completed and ongoing clinical
      studies and through evaluation of case studies submitted by clinicians. In the
      process, much has been learned about some interesting aspects of OptiVol fluid
      status monitoring and its use with patients with heart failure.

PMID- 17512423
TI  - Collaboration among general cardiologists, heart failure specialists, and
      electrophysiologists: what are the barriers?
AB  - Although ongoing research has focused on the reliability and accuracy of data
      derived from implanted devices, important challenges remain, among which is the
      development of a framework for handling the data, including delineation of
      responsibility for interpretation and management of the data. The barriers to a
      successful device-monitoring program include difficulties in data access,
      unfamiliarity with a new treatment approach, lack of sufficient knowledge and
      experience in data interpretation, and difficulty incorporating the program into
      the existing workflow. The dynamics of collaboration between heart failure and
      electrophysiology (EP) specialists may differ locally and regionally, but a
      common set of barriers resulting from traditional models of care constrains
      incorporation of device-based data into clinical practice. Active dialogue
      between EP and heart failure specialists that involves the sharing of experiences
      and practice models is an important first step to overcoming these barriers. In
      the future, a "virtual clinic" model of patient care can only be realized with
      the successful incorporation of remotely accessed device data.

PMID- 17512430
TI  - Biological basis of breast cancer: an introduction.

PMID- 17512431
TI  - New generation of molecular prognostic and predictive tests for breast cancer.
AB  - Breast cancer is a clinically heterogeneous disease, and it is generally accepted
      that the different clinical courses of patients with histologically similar
      tumors are due to molecular differences among cancers. Therefore, detailed
      molecular analysis of the cancer could yield prognostic information. Recent
      advances in molecular analytical techniques have led to rapid expansion of novel
      diagnostics designed to personalize breast cancer care. Diagnostic companies are
      also increasingly adopting a clinical trial-based approach to develop their
      products. This article reviews some of the most important advances in this field
      in the past few years, including the emergence of several multigene and
      prognostic predictors, as well as methods allowing enumeration of circulating
      tumor cells that are currently offered as commercially available diagnostic
      assays.

PMID- 17512432
TI  - Biomarker studies and other difficult inferential problems: statistical caveats.
AB  - The inferential issues associated with biomarker studies are enormously complex.
      False-positive conclusions are rampant in the literature. It is wonderful to have
      many potential biomarkers in trying to explain the heterogeneity of cancer and
      outcomes of its treatment. But a large number of biomarkers give rise to
      statistical headaches. False-positives proliferate. A useful approach is to
      reduce many biomarkers into a single dimension, and to then attempt to confirm
      the prognostic or predictive value of the single-dimensional quantity. This is
      not a panacea for all statistical and scientific ailments, but it minimizes some
      of the problems. A related concern is subset analysis. I give a statistical
      argument that estrogen-receptor status is predictive of the benefits of
      chemotherapy in node-positive breast cancer.

PMID- 17512433
TI  - A pathologist's perspective on emerging genomic tests for breast cancer.
AB  - Emerging molecular tests for breast cancer indicate how future progress in
      diagnostic pathology might guide patient care. However, the challenge will be to
      bring the best results from this exciting research into clinical use as accurate
      and reliable standardized tests that integrate into the diagnostic work-up.

PMID- 17512435
TI  - The concept of symptom cluster.
AB  - OBJECTIVES: To define the concept of a symptom cluster, evaluate the evidence
      base in support of it, and address research and clinical implications. DATA
      SOURCES: Review of descriptive research that examined fatigue, insomnia, pain, or
      depression in relation to other symptoms. CONCLUSION: More investigation is
      needed. There is evidence of overlapping variance indicative of a relationship
      between or among symptoms. Few studies have addressed the outcomes of symptom
      clusters. There is limited evidence of symptom concurrence or a common biological
      pathway for clustered symptoms. IMPLICATIONS FOR NURSING PRACTICE: Consideration
      should be given to assessment and management of fatigue, insomnia, pain, and
      depression as potential "sentinel symptoms" that could affect patient outcomes.

PMID- 17512436
TI  - Is there a biological basis for the clustering of symptoms?
AB  - OBJECTIVES: To examine symptom clusters in oncology patients; to determine if
      these symptom clusters might share a common biologic mechanism; and to describe
      potential biologic mechanisms that warrant investigation. DATA SOURCES: Synthesis
      of the theoretical and research papers on symptom clusters. CONCLUSION:
      Definitive conclusions about whether there is a biologic basis for the clustering
      of symptoms cannot be determined at this time. The animal model of sickness
      behavior holds promise as a potential biologic mechanism for clustering symptoms.
      IMPLICATIONS FOR NURSING PRACTICE: Until more definitive studies of symptom
      clusters are performed, clinicians need to monitor patients for the co-occurrence
      of multiple symptoms and develop appropriate management plans.

PMID- 17512437
TI  - Clinical assessment of symptom clusters.
AB  - OBJECTIVES: To review the principles of symptom cluster assessment, choosing
      appropriate symptom measures, and methods to identify symptom clusters. DATA
      SOURCES: Review articles, research articles, and specialty texts. CONCLUSION:
      Identification of symptom clusters is clinically challenging and includes the use
      of reliable symptom assessment tools and clinical judgment. Evidence to guide
      assessment of symptom clusters is based on limited clinical research and expert
      practice. Additional research is needed to guide the accurate assessment of
      symptom clusters and the patient's symptom experience. IMPLICATIONS FOR NURSING
      PRACTICE: Comprehensive assessment of symptom clusters in individuals with cancer
      will lead to tailored, comprehensive symptom management strategies that may have
      a profound impact on cancer-related quality of life.

PMID- 17512438
TI  - Clinical management of symptom clusters.
AB  - OBJECTIVES: To discuss the current evidence for the management of symptoms in
      clusters and future directions in symptom cluster management research. DATA
      SOURCES: Research and review articles. CONCLUSION: Currently no research has been
      reported on management of formally identified symptom clusters in oncology.
      Several researchers have described psychoeducational and exercise interventions
      that have decreased multiple concurrent symptoms. Understanding common biological
      mechanisms that underlie symptom clusters, such as inflammatory pathways, may
      suggest more effective treatments for symptom clusters. IMPLICATIONS FOR NURSING
      PRACTICE: Clinicians and researchers need to collaborate to better understand
      symptom clusters and develop effective interventions.

PMID- 17512439
TI  - Symptom clusters and physical function for patients receiving chemotherapy.
AB  - OBJECTIVES: To examine the literature on symptom clusters and the impact of co
      occurring symptoms on the physical function of patients with cancer during
      treatment. DATA SOURCES: Research and review articles. CONCLUSION: Unmanaged
      symptoms occur in what are often called symptom clusters. A focus on known and
      frequently present co-occurring symptoms, such as pain, fatigue, and sleep
      disturbance, might be the most efficient and effective way to manage specific
      symptoms and improve patient functioning. IMPLICATIONS FOR NURSING PRACTICE:
      Nurses should select assessments that identify multiple symptoms and define their
      co-occurrence.

PMID- 17512440
TI  - Fatigue, depression, and insomnia: evidence for a symptom cluster in cancer.
AB  - OBJECTIVES: To review the evidence for considering fatigue, depression, and
      insomnia as a symptom cluster in cancer. DATA SOURCES: Empirical studies,
      clinical articles, and review articles. CONCLUSION: The single- and multi-symptom
      measurement approaches are of limited usefulness in distinguishing fatigue,
      depression, and insomnia. Studies in which these symptoms have been measured
      concurrently in patients with cancer yield consistent evidence of high positive
      correlations. Results do not appear to be solely a function of overlap in
      measurement approaches. IMPLICATIONS FOR NURSING PRACTICE: Successful management
      of fatigue, depression, and insomnia in cancer patients are likely to combine
      pharmacologic and nonpharmacologic therapies.

PMID- 17512441
TI  - Symptom clusters related to specific cancers.
AB  - OBJECTIVES: To examine the current research related to symptom clusters in
      specific cancer diagnoses. DATA SOURCES: Research studies, review articles.
      CONCLUSION: Factors that can impact symptoms and their relationship include the
      stage of disease, treatment used, modification of treatment for the individual
      patient, patient co-morbidities as well as psychological, sociological, and
      cultural factors. Understanding is needed regarding which of these factors
      individually or in combination contribute to symptoms clustering together. The
      mechanism underlying symptom perception and interpretation need further
      exploration. Research focus should be on one type of cancer. IMPLICATIONS FOR
      NURSING PRACTICE: Symptom cluster research offers little at this point to be
      helpful in patient diagnosis, assessment, monitoring, or management of disease.

PMID- 17512442
TI  - Treatment-related symptom clusters.
AB  - OBJECTIVES: To provide a clinical overview of treatment-related symptom clusters.
      DATA SOURCES: Journal articles, research reports, state of the science papers,
      and clinical practice experience. CONCLUSION: Although understanding the etiology
      and interaction of symptoms may lead to targeted interventions, the nurse must
      often manage symptoms in which the cause or causes cannot be changed or in which
      there are multiple overlapping etiologies that lead to complex and challenging
      clinical presentations. Systematic and ongoing evaluation of symptoms, their
      treatment-related trajectory, and their response to interventions is essential.
      IMPLICATIONS FOR NURSING PRACTICE: Systematic assessment of symptoms and symptom
      cluster presence, severity, and distress can guide the practitioner to intervene
      using evidence-based practice. Individualized care and evaluation of response is
      needed.

PMID- 17512443
TI  - Symptom clusters in children with cancer.
AB  - OBJECTIVES: To discuss the symptoms of fatigue, sleep disturbance, and pain in
      children undergoing cancer treatment, and a framework for the clustering of these
      symptoms. DATA SOURCES: Published articles, research studies, and clinical
      experience. CONCLUSION: Symptoms experienced by children undergoing cancer
      treatment are distressing, prevalent, and rarely occur in isolation. Multiple
      symptoms may share underlying mechanisms, influence the severity of the distress
      experienced, and interfere with a child's ongoing development. Developing
      knowledge of the relationships among symptoms may be important for improving
      quality of life during cancer treatment while supporting the child's development.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses must be aware of the symptom distress
      occuring in children with cancer to manage its symptoms and its treatments.

PMID- 17512445
TI  - Adjuvant chemotherapy for early-stage breast cancer.
AB  - Systemic chemotherapy is an integral component of the adjuvant treatment strategy
      for women who have early-stage breast cancer and accounts for significant
      improvements in breast cancer-specific mortality. Decisions regarding adjuvant
      therapy are increasingly complex with the advent of new therapeutic strategies, a
      growing body of literature on the molecular biology and natural history of breast
      cancer, and advances in therapeutic techniques and early detection. Ultimately,
      the risk-benefit calculus will continue to evolve in response to these advances
      and one hopes that clinicians will soon be able to tailor treatment
      recommendations to the biology of an individual cancer and the needs of the
      affected individual.

PMID- 17512446
TI  - Adjuvant endocrine treatment of early breast cancer.
AB  - Endocrine therapy plays a pivotal role in the early treatment of estrogen
      receptor (ER)-positive breast cancer. Although evidence suggests that
      chemotherapy may work partly through ovarian ablation in young women who have ER
      positive tumors, combined chemotherapy and endocrine therapy are generally
      advocated. In postmenopausal women, aromatase inhibition has become the new "gold
      standard" of treatment. More research is needed to define optimal regimens
      (aromatase inhibitor monotherapy versus tamoxifen sequential application),
      optimal duration of therapy and potential advantages of particular compounds. The
      optimal use of estrogen suppression (ovarian ablation with or without aromatase
      inhibition) and tamoxifen (administered sequentially or in concert with ovarian
      ablation) in premenopausal women has yet to be defined.

PMID- 17512447
TI  - Trastuzumab (herceptin) for early-stage breast cancer.
AB  - Breast cancer patients who have HER2 gene amplification and, consequently,
      protein overexpression, generally show an aggressive course with short disease
      free and overall survivals. Trastuzumab, a humanized monoclonal antibody against
      the extracellular domain of HER2 protein, has been shown to benefit patients who
      have HER2-positive metastatic breast cancer, and recently, the results of five
      adjuvant trials involving more than 13,000 women have been released. Here, the
      authors summarize the main results and outline the differences among these
      trials, which have demonstrated an important role of trastuzumab in the treatment
      of women who have HER2-overexpressing/amplified early breast cancer.

PMID- 17512448
TI  - Chemotherapy for metastatic breast cancer.
AB  - Cytotoxic chemotherapy is a mainstay of treatment for advanced breast cancer.
      Treatment of metastatic (also called stage IV, advanced, or recurrent) breast
      cancer is not considered curative. Rather, the goals of treatment with
      chemotherapy are to prolong survival, alleviate or prevent tumor-related symptoms
      or complications, and improve quality of life. While the purpose of chemotherapy
      is to prevent or alleviate symptoms, chemotherapy paradoxically carries
      considerable toxicities that cause substantial symptoms in patients, notoriously
      including fatigue, nausea, vomiting, diarrhea, hair loss, mucositis, neutropenia,
      and neuropathy. Balancing the benefits and the side effects of chemotherapy is
      further complicated by the natural history of advanced breast cancer, which can
      be quite prolonged and typically involves multiple lines of chemotherapy,
      especially in patients whose tumors respond to treatment.

PMID- 17512449
TI  - Hormonal therapy for advanced breast cancer.
AB  - Hormonal therapy for advanced breast cancer has evolved significantly in the more
      than 100 years since the first publications documenting the effect of ovarian
      ablation on advanced breast cancer in premenopausal women. Since that time, not
      only have we developed the methods to measure estrogen and progesterone receptors
      in cancer cells, but more recently we have understood that expression of these
      receptors determines response to hormone therapy. The availability of more
      selective antiestrogen therapies has changed and significantly improved the
      treatment options for women who have advanced hormone-responsive breast cancer.
      Current research is focusing on reversing resistance to hormone therapy with the
      addition of targeted biologic agents to standard hormonal treatment.

PMID- 17512450
TI  - HER2-positive advanced breast cancer.
AB  - It is important when treating a patient who has advanced breast cancer to
      establish the biologic characteristics of the tumor. In addition to knowing the
      hormone receptor status (estrogen and progesterone), human epidermal receptor 2
      (HER2) should be evaluated. The measurement of this parameter is essential to
      optimizing the systemic management. This article reviews the biology of HER2,
      testing for HER2, clinical studies evaluating HER2-based therapies, side effects
      (specifically cardiotoxicity), and strategies for HER2-based therapies.

PMID- 17512451
TI  - Bevacizumab for advanced breast cancer.
AB  - Tumor angiogenesis is essential for the growth and metastasis of solid tumors. In
      breast cancer, increased levels of vascular endothelial growth factor (VEGF) have
      been associated with poor prognosis in lymph node-positive and lymph node
      negative patients. In addition to its prognostic significance, VEGF is now a
      validated target in the treatment of breast cancer. Bevacizumab, an anti-VEGF
      antibody, has demonstrated significant clinical benefit in several solid tumors.
      In this article the authors discuss the data pertaining to bevacizumab and other
      antiangiogenic agents for the treatment of patients who have advanced breast
      cancer.

PMID- 17512452
TI  - Emerging targeted therapies for breast cancer.
AB  - Breast cancer is the most common neoplasia among women in the world. For the last
      few years there has been an increasing interest in the development of agents
      against molecular targets considered to be involved in the process of malignant
      transformation or tumor progression. Experimental data indicate that various
      intracellular signaling pathways may be activated or overexpressed in patients
      who have breast cancer. Targeted therapies against these pathways have recently
      become one of the most active and promising areas of development in oncology.

PMID- 17512453
TI  - Bisphosphonates for breast cancer: questions answered, questions remaining.
AB  - Bone is an important organ that is essential to adult hematopoiesis, electrolyte
      balance, and locomotion. Individuals who have metastatic breast cancer involving
      the bone are at increased risk for skeletal complications and those who have a
      history of early-stage breast cancer may be at increased risk for fragility
      fractures. Maintaining bone integrity is critical to control the morbidity and
      mortality associated with fractures and other skeletal complications. The
      bisphosphonates have been shown to be efficacious in decreasing the risk for
      skeletal complications in cancer and in osteoporosis. The article reviews the use
      of bisphosphonates in patients who have breast cancer.

PMID- 17512454
TI  - Brain metastases: old problem, new strategies.
AB  - Brain metastases from breast cancer are a common complication of the disease and
      alter the management of patients more than any other site of distant progression.
      Certain subgroups of patients are at high risk for developing CNS disease,
      warranting targeted research and perhaps screening for occult disease. Data from
      studies that include other solid tumor histologies provide the bulk of supporting
      evidence for the use of therapies, such as steroids, antiepileptic drugs,
      surgery, and radiation. However, there are several issues specific to brain
      metastases from breast cancer illustrating that this disease should be considered
      pathophysiologically distinct, and future research should be tailored
      accordingly.

PMID- 17512456
TI  - Targeting lipoic acid to mitochondria: synthesis and characterization of a
      triphenylphosphonium-conjugated alpha-lipoyl derivative.
AB  - Lipoic acid (LA) is a widely used antioxidant that protects mitochondria from
      oxidative damage in vivo. Much of this protection is thought to be due to the
      reduction of LA to dihydrolipoic acid (LAH(2)). This reduction is catalyzed in
      vivo by thioredoxin, thioredoxin reductase (TrxR), and lipoamide dehydrogenase.
      We hypothesized that specifically targeting LA to mitochondria, the site of most
      cellular reactive oxygen species production, would make it a more effective
      antioxidant. To do this, we made a novel molecule, MitoLipoic acid, by attaching
      lipoic acid to the lipophilic triphenylphosphonium cation. MitoL was accumulated
      rapidly within mitochondria several-hundred fold driven by the membrane
      potential. MitoL was reduced to the active antioxidant dihydroMitoLipoic acid by
      thioredoxin and by lipoamide dehydrogenase but not by TrxR. In isolated
      mitochondria or cells MitoL was only slightly reduced (5-10%), while, in
      contrast, LA was extensively reduced. This difference was largely due to the
      reaction of LA with TrxR, which did not occur for MitoL. Furthermore, in cells
      MitoL was quantitatively converted to an S-methylated product. As a consequence
      of its lack of reduction, MitoL was not protective for mitochondria or cells
      against a range of oxidative stresses. These results suggest that the protective
      action of LA in vivo may require its reduction to LAH(2) and that this reduction
      is largely mediated by TrxR.

PMID- 17512455
TI  - Safety of trivalent chromium complexes: no evidence for DNA damage in human HaCaT
      keratinocytes.
AB  - Several studies have demonstrated beneficial effects of supplemental trivalent Cr
      in subjects with reduced insulin sensitivity with no documented signs of
      toxicity. However, recent studies have questioned the safety of supplemental
      trivalent Cr complexes. The objective of this study was to evaluate the cytotoxic
      and genotoxic potential of the Cr(III) complexes (histidinate, picolinate, and
      chloride) used as nutrient supplements compared with Cr(VI) dichromate. The
      cytotoxic and genotoxic effects of the Cr complexes were assessed in human HaCaT
      keratinocytes. The concentrations of Cr required to decrease cell viability were
      assessed by determining the ability of a keratinocyte cell line (HaCaT) to reduce
      tetrazolium dye, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.
      DNA damage using the Comet assay and the production of 8-hydroxy-2'
      deoxyguanosine were also determined with and without hydrogen peroxide-induced
      stress. The LC50 for human cultured HaCaT keratinocytes was 50 microM for
      hexavalent sodium dichromate and more than 120-fold higher for Cr chloride (6 mM)
      and Cr histidinate (10 mM). For Cr picolinate at saturating concentration (120
      microM) the LC50 was not attained. High Cr(III) concentrations, 250 microM Cr as
      Cr chloride and Cr histidinate and 120 microM Cr picolinate (highest amount
      soluble in the system), not only did not result in oxidative DNA damage but
      exhibited protective antioxidant effects when cells were exposed to hydrogen
      peroxide-induced oxidative stress. These data further support the low toxicity of
      trivalent Cr complexes used in nutrient supplements.

PMID- 17512457
TI  - Preeclampsia inactivates glucose-6-phosphate dehydrogenase and impairs the redox
      status of erythrocytes and fetal endothelial cells.
AB  - Inactivation of glucose-6-phosphate dehydrogenase (G6PD) may contribute to
      vascular dysfunction in preeclampsia, and oxidative stress has been implicated in
      the pathogenesis of this disease. We have compared the susceptibility of
      erythrocytes and human umbilical vein endothelial cells (HUVEC) to oxidative
      stress in women with normotensive or preeclamptic pregnancies. The redox status
      of erythrocytes was also correlated with neutrophil-mediated superoxide (O(2)(.
      )) production in women recruited to the "Vitamins in Preeclampsia" (VIP) trial.
      Erythrocytes and HUVEC from women with preeclampsia demonstrated impaired redox
      regulation and diminished response to glucose, detectable at 14-20 weeks
      gestation prior to onset of the clinical disease. Hexokinase and G6PD activities
      were decreased in erythrocytes and G6PD activity was decreased in HUVEC from
      preeclamptic pregnancies. Phorbol-ester-stimulated O(2)(.-) was enhanced in
      preeclamptic neutrophils. Impaired redox regulation in erythrocytes and HUVEC in
      preeclampsia may be due to diminished hexokinase and G6PD activities resulting
      from increased release of reactive oxygen species from activated neutrophils. Our
      findings provide the first evidence that decreased G6PD activity in preeclampsia
      is associated with impaired redox regulation in erythrocytes and fetal
      endothelial cells. The deficiency in G6PD in preeclampsia potentially accounts
      for the lack of protection against oxidative stress afforded by antioxidant
      vitamin C/E supplementation in the VIP trial.

PMID- 17512458
TI  - Antiinflammatory effects of the cyclopentenone isoprostane 15-A(2)-IsoP in human
      gestational tissues.
AB  - Proinflammatory prostaglandins and cytokines are involved in the initiation of
      human labor and delivery. Although cyclopentenone prostaglandins regulate the
      formation of these prolabor mediators via nuclear factor-kappaB (NF-kappaB)
      and/or peroxisome proliferator-activated receptor-gamma, recent evidence suggests
      that they do not exist in vivo. Cyclopentenone isoprostanes (IsoPs), which are
      highly reactive structural isomers of bioactive cyclopentenone prostaglandins, do
      exist physiologically and have been shown to inhibit the inflammatory response in
      macrophages. Therefore the aim of this study was to determine the effect of the
      synthetic cyclopentenone IosP 15-A(2)-IsoP on the expression of prolabor
      mediators in human gestational tissues. Human placenta and gestational membranes
      (n=5) were incubated in the absence or presence of 12.5, 25, and 50 microM 15
      A(2)-IsoP with 10 microg/ml lipopolysaccharide (LPS). Treatment of placenta and
      fetal membranes with 15-A(2)-IsoP caused a dose-dependent decrease in LPS
      stimulated release of the cytokines IL-1beta, IL-6, IL-8, and TNF-alpha and the
      prostaglandins PGE(2) and PGF(2)alpha. NF-kappaB p65 DNA binding activity was
      significantly inhibited by treatment with 50 microM 15-A(2)-IsoP. Collectively,
      these data suggest that 15-A(2)-IsoP exhibits antiinflammatory properties via
      antagonism of NF-kappaB activity. Cyclopentenone IsoPs may serve as negative
      feedback regulators of the inflammatory response in human gestational tissues.

PMID- 17512459
TI  - Molecular mechanism of human Nrf2 activation and degradation: role of sequential
      phosphorylation by protein kinase CK2.
AB  - Nrf2 is a key transcription factor in the cellular response to oxidative stress.
      In this study we identify two phosphorylated forms of endogenous human Nrf2 after
      chemically induced oxidative stress and provide evidence that protein kinase CK2
      mediated sequential phosphorylation plays potential roles in Nrf2 activation and
      degradation. Human Nrf2 has a predicted molecular mass of 66 kDa. However,
      immunoblots showed that two bands at 98 and 118 kDa, which are identified as
      phosphorylated forms, are increased in response to Nrf2 inducers. In addition,
      human Nrf2 was found to be a substrate for CK2 which mediated two steps of
      phosphorylation, resulting in two forms of Nrf2 migrating with differing M(r) at
      98 kDa (Nrf2-98) and 118 kDa (Nrf2-118). Our results support a role in which
      calmodulin binding regulates CK2 activity, in that cold (25 degrees C) Ca(2+)
      free media (cold/Ca(2+)-free) decreased both cellular calcium levels and CK2
      calmodulin binding and induced Nrf2-118 formation, the latter of which was
      prevented by CK2-specific inhibitors. Gel shift assays showed that the Nrf2-118
      generated under cold/Ca(2+)-free conditions does not bind to the antioxidant
      response element, indicating that Nrf2-98 has transcriptional activity. In
      contrast, Nrf2-118 is more susceptible to degradation. These results provide
      evidence for phosphorylation by CK2 as a critical controlling factor in Nrf2
      mediated cellular antioxidant response.

PMID- 17512460
TI  - Complementation of the oxidatively damaged DNA repair defect in Cockayne syndrome
      A and B cells by Escherichia coli formamidopyrimidine DNA glycosylase.
AB  - Repair of the oxidized purine 8-oxo-7,8-dihydroguanine (8-oxoGua) is inefficient
      in cells belonging to the B complementation group of Cockayne syndrome (CS-B), a
      developmental and neurological disorder characterized by defective transcription
      coupled repair. We show here that cells belonging to the A complementation group
      (CS-A) are also defective in repair of 8-oxoGua and we demonstrate that
      expression of the Escherichia coli formamidopyrimidine DNA glycosylase (FPG)
      completely corrects the repair deficiency in both CS-A and CS-B cells.
      Phenotypically, CS-A cells are normally sensitive to toxicity and micronuclei
      induced by the oxidizing agent potassium bromate. CS-B cells display sensitivity
      to elevated concentrations of potassium bromate but this is not compensated by
      FPG expression, suggesting toxicity of lesions that are not FPG substrates. The
      data indicate that 8-oxoGua is not a major toxic and clastogenic lesion in CS
      cells.

PMID- 17512461
TI  - Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin
      induced cardiac injury.
AB  - Cardiac injury is a major complication for oxidative-stress-generating anticancer
      agents exemplified by Adriamycin (ADR). Recently, several histone deacetylase
      inhibitors (HDACIs) including phenylbutyrate (PBA) have shown promise in the
      treatment of cancer with little known toxicity to normal tissues. PBA has been
      shown to protect against oxidative stress in normal tissues. Here, we examined
      whether PBA might protect heart against ADR toxicity in a mouse model. The mice
      were i.p. injected with ADR (20 mg/kg). PBA (400 mg/kg/day) was i.p. injected 1
      day before and daily after the ADR injection for 2 days. We found that PBA
      significantly decreased the ADR-associated elevation of serum lactate
      dehydrogenase and creatine kinase activities and diminished ADR-induced
      ultrastructural damages of cardiac tissue by more than 70%. Importantly, PBA
      completely rescued ADR-caused reduction of cardiac functions exemplified by
      ejection fraction and fraction shortening, and increased cardiac manganese
      superoxide dismutase (MnSOD) protein and activity. Our results reveal a
      previously unrecognized role of HDACIs in protecting against ADR-induced cardiac
      injury and suggest that PBA may exert its cardioprotective effect, in part, by
      the increase of MnSOD. Thus, combining HDACIs with ADR could add a new mechanism
      to fight cancer while simultaneously decrease ADR-induced cardiotoxicity.

PMID- 17512462
TI  - Selenium deficiency alters epithelial cell morphology and responses to influenza.
AB  - It is unknown whether nutritional deficiencies affect the morphology and function
      of structural cells, such as epithelial cells, and modify the susceptibility to
      viral infections. We developed an in vitro system of differentiated human
      bronchial epithelial cells (BEC) grown either under selenium-adequate (Se+) or
      selenium-deficient (Se-) conditions, to determine whether selenium deficiency
      impairs host defense responses at the level of the epithelium. Se- BECs had
      normal SOD activity, but decreased activity of the selenium-dependent enzyme
      GPX1. Interestingly, catalase activity was also decreased in Se- BECs. Both Se-
      and Se+ BECs differentiated into a mucociliary epithelium; however, Se- BEC
      demonstrated increased mucus production and increased Muc5AC mRNA levels. This
      effect was also seen in Se+ BEC treated with 3-aminotriazole, an inhibitor of
      catalase activity, suggesting an association between catalase activity and mucus
      production. Both Se- and Se+ were infected with influenza A/Bangkok/1/79 and
      examined 24 h postinfection. Influenza-induced IL-6 production was greater while
      influenza-induced IP-10 production was lower in Se- BECs. In addition, influenza
      induced apoptosis was greater in Se- BEC as compared to the Se+ BECs. These data
      demonstrate that selenium deficiency has a significant impact on the morphology
      and influenza-induced host defense responses in human airway epithelial cells.

PMID- 17512463
TI  - Upregulation of thioredoxin system via Nrf2-antioxidant responsive element
      pathway in adaptive-retinal neuroprotection in vivo and in vitro.
AB  - We tested the hypothesis that stress responses mediated by the Nrf2-antioxidant
      responsive element (ARE) pathway are involved in the initiation of retinal
      neuroprotection provided by bright-cyclic-light rearing. Albino rats born and
      raised in dim (5 lux) or bright (400 lux) cyclic light were exposed to damaging
      light (3000 lux, 6 h). After exposure, the outer nuclear layer thickness and area
      and the electroretinogram a- and b-wave amplitudes were significantly reduced in
      the dim-light-reared rats compared to the bright-light-reared rats, demonstrating
      a light adaptation neuroprotection phenomenon. In bright-cyclic-light-reared
      rats, the retinal levels of thioredoxin (Trx) (2.4-fold), Trx reductase (TrxR)
      (2.9-fold), and proteins modified by 4-hydroxynonenal (4-HNE) (1.5-fold) were
      upregulated by Western blot analyses, and the nuclear translocation of Nrf2 (2.2
      fold) and the DNA binding activity of Nrf2, small Maf, and cJun to the ARE were
      increased as determined by electrophoretic mobility shift assays. In mouse
      photoreceptor-derived 661W cells, pretreatment with a sublethal dose of 4-HNE
      protected against H(2)O(2)-induced cell damage. Treatment with 4-HNE upregulated
      cellular Trx, TrxR, and heme oxygenase-1 (HO-1) levels in addition to DNA binding
      activity of Nrf2, small Maf, and cJun to the ARE. Downregulation of Nrf2 using
      RNA interference technology diminished 4-HNE-mediated upregulation of Trx and Trx
      reductase but did not affect the upregulation of HO-1 by 4-HNE. Cytoprotection by
      4-HNE pretreatment against H(2)O(2)-induced cell damage was not observed in 661W
      cells with a silenced Nrf2 gene. The results suggest that upregulation of the Trx
      system by 4-HNE via the Nrf2-ARE pathway may be involved in the molecular
      mechanism of the retinal neuroprotection phenomenon.

PMID- 17512464
TI  - Reactive oxidants regulate membrane repolarization and store-operated uptake of
      calcium by formyl peptide-activated human neutrophils.
AB  - Although the rapid and considerable membrane depolarization response which
      accompanies activation of the phagocyte NADPH oxidase is due to transmembrane
      electron fluxes, little is known about the involvement of reactive oxidant
      species (ROS) in the subsequent repolarization response. In the current study, we
      have investigated the effects of superoxide dismutase (SOD), catalase,
      methionine, and the myeloperoxidase (MPO) inhibitors, sodium azide and 4
      aminobenzoyl hydrazide (ABAH), as well as those of H(2)O(2) and HOCl (both at 100
      microM) on the alterations in membrane potential which accompany activation of
      human neutrophils with the chemoattractant, FMLP (1 microM), and on store
      operated uptake of Ca(2+). The generation of ROS by FMLP-activated neutrophils
      was monitored according to the magnitude of oxygen consumption and
      autoiodination, while spectrofluorimetric procedures were used to measure
      alterations in membrane potential and influx of Ca(2+). Treatment of the cells
      with H(2)O(2), and HOCl, significantly impeded membrane repolarization, while
      sodium azide, ABAH, methionine, and catalase exerted the opposite effects,
      potentiating both the rates and the magnitudes of membrane repolarization and
      store-operated uptake of Ca(2+). These observations demonstrate that NADPH
      oxidase regulates neutrophil membrane potential and Ca(2+) influx not only via
      its electrogenic activity, but also as a consequence of the generation of ROS.

PMID- 17512465
TI  - Busulfan-induced senescence is dependent on ROS production upstream of the MAPK
      pathway.
AB  - Induction of cellular senescence is a common response of a normal cell to a DNA
      damaging agent, which may contribute to cancer chemotherapy- and ionizing
      radiation-induced normal tissue injury. The induction has been largely attributed
      to the activation of p53. However, the results from the present study suggest
      that busulfan (BU), an alkylating agent that causes DNA damage by cross-linking
      DNAs and DNA and proteins, induces senescence in normal human diploid WI38
      fibroblasts through the extracellular signal-regulated kinase (Erk) and p38
      mitogen-activated protein kinase (p38 MAPK) cascade independent of the p53-DNA
      damage pathway. The induction of WI38 cell senescence is initiated by a transient
      depletion of intracellular glutathione (GSH) and followed by a continuous
      increase in reactive oxygen species (ROS) production via nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase, which leads to the activation of the Erk
      and p38 MAPK pathway. Incubation of WI38 cells with N-acetylcysteine (NAC)
      replenishes intracellular GSH, abrogates the increased production of ROS,
      ameliorates Erk and p38 MAPK activation, and attenuates senescence induction by
      BU. Thus, inhibition of senescence induction using a potent antioxidant or
      specific inhibitor of the Erk and p38 MAPK pathway has the potential to be
      developed as a mechanism-based strategy to ameliorate cancer therapy-induced
      normal tissue damage.

PMID- 17512466
TI  - Differential regulation of Mn-superoxide dismutase in neurons and astroglia by
      HIV-1 gp120: Implications for HIV-associated dementia.
AB  - HIV-associated dementia, like several other neurodegenerative diseases, is
      characterized by selective degeneration of neurons amidst survival of glial cells
      like astroglia. The molecular basis of such selective susceptibility within the
      same milieu remains largely unknown. Neurons are rarely infected by the virus.
      However, they are vulnerable to viral products, like HIV-1 coat protein gp120.
      Interestingly, gp120 induced oxidative stress in neurons, but not in astroglia.
      This led us to postulate that astroglia were armed with a more efficient
      antioxidant system than neurons. Here, we report that the constitutive level of
      MnSOD (SOD2), the major cellular antioxidant enzyme, is significantly higher in
      astroglia than in neurons. Furthermore, gp120 treatment enhanced MnSOD levels in
      astroglia but decreased the same in neurons. This increase in astroglial MnSOD
      was dependent on NF-kappaB, the crucial transcription factor required for sod2
      gene transcription. Blocking NF-kappaB with p65-antisense, p65-si-RNA, or a
      specific inhibitor, NBD peptide, led to reduced MnSOD levels and enhanced
      vulnerability of astroglia to gp120. Additionally, neurons were found to have a
      lower constitutive level of NF-kappaB p65 than astrocytes. Overexpression of p65
      increased the level of MnSOD in neurons. This, in turn, elicited greater neuronal
      resistance to gp120. Taken together, our study suggests that astroglia manifest a
      higher threshold for gp120-induced lethality than neurons due to greater MnSOD
      availability, which is demonstrated due to greater level of NF-kappaB p65.

PMID- 17512468
TI  - Workload and patient safety among critical care nurses.
AB  - Several dimensions of workload experienced by nurses working in ICUs are
      described in this article, including the physical workload related to patient
      handling. The effects of workload on various outcomes, such as the health,
      safety, and quality of working life of nurses, and the safety of care provided by
      ICU nurses are discussed. A systemic approach to the assessment of workload is
      proposed that is aimed at identifying the work system factors that contribute to
      the different facets of workload and the interdependencies among the various
      dimensions of workload.

PMID- 17512469
TI  - Patient handling tasks with high risk for musculoskeletal disorders in critical
      care.
AB  - Critical care nurses are at high risk for development of work-related
      musculoskeletal disorders (WMSDs). Many patient handling tasks in critical care
      require physical demands that may result in excessive internal forces, increasing
      the risk for WMSDs. There are solutions for performing these tasks safely, using
      technology. This article describes risk factors associated with high-risk patient
      handling tasks and presents solutions for reducing risk for WMSDs. Studies show
      that implementing a safe patient handling and movement program that incorporates
      new technology can pay for itself in a short period of time and provide long-term
      benefit for health care facilities and nursing staff.

PMID- 17512470
TI  - Psychosocial factors in musculoskeletal disorders.
AB  - Work-related musculoskeletal disorders (MSD) have a multifactorial etiology that
      includes not only physical stressors but also psychosocial risk factors, such as
      job strain, social support at work, and job dissatisfaction. Once an injury has
      occurred, psychosocial factors, such as depression and maladaptive pain
      responses, are pivotal in the transition from acute to chronic pain and the
      development of disability. Interventions to prevent MSD incidence and address
      psychosocial risk factors for delayed recovery are described.

PMID- 17512471
TI  - Ergonomic assessment of a critical care unit.
AB  - Although direct patient care providers in all settings suffer musculoskeletal
      injuries at unacceptable rates, high-risk tasks in nursing homes are the most
      frequently researched. Less is known about the high-risk tasks performed by
      critical care nurses. To identify the tasks in critical care that differ from
      those in nursing homes, this qualitative study used the Ergonomic Workplace
      Assessment Protocol for Patient Care Environments to assess a medical ICU.
      Results and recommendations for change are presented.

PMID- 17512472
TI  - Evaluation of critical care space requirements for three frequent and high-risk
      tasks.
AB  - Spatial requirements for clinical tasks have been recommended from many sources
      over the past 15 years, but little empiric evidence is offered to support
      recommendations. This article describes a series of functional space experiments
      using clinical scenarios to test the spatial requirements for a bed space in a
      critical care setting. The analysis found that an average of 23.26 m(2) was
      needed for a bed-to-bed transfer followed by 22.87 m(2) for a resuscitation task.
      The overall average space requirement for the three tasks for a patient and
      caregiver zone (ergonomic envelope) was 22.83 m(2), excluding family and hygiene
      zones and in-room storage.

PMID- 17512473
TI  - Technology solutions for high-risk tasks in critical care.
AB  - There are several high-risk nursing tasks in the critical care environment
      discussed in this article. These tasks include lateral transfers, repositioning
      patients up or side to side in bed, bed-to-chair or -wheelchair transfers,
      pericare of bariatric patients, toileting in bed, sustained limb holding for
      dressing wounds, and patient transport. Although many, if not all, of these tasks
      currently are performed manually, there are technological solutions available
      that undoubtedly can reduce the risks for caregiver and patient injuries. These
      solutions should be implemented in critical care to promote the safety of all
      involved in patient care.

PMID- 17512474
TI  - Justification for a minimal lift program in critical care.
AB  - This chapter reviews literature pertaining to patient-handling tasks spanning the
      areas of epidemiology, biomechanics, perceived stresses, education and training
      programs, and introduction of mechanical patient lifting devices. All findings
      agree that patient handling is inherently dangerous and has been attributed to
      the majority of injuries incurred by nursing personnel; however, most studies
      have been performed in hospitals or long term care settings, but have not been
      specific to the area of critical care. The critical care environment poses unique
      challenges for nursing personnel and therefore, to ergonomists.

PMID- 17512475
TI  - Sustaining staff nurse support for a patient care ergonomics program in critical
      care.
AB  - Applying management concepts from marketing and business sources can assist
      critical care units with establishing a planned change in the way nurses perform
      manual handling tasks, and thus, help insure that it is sustained.

PMID- 17512476
TI  - Safe patient handling program in critical care using peer leaders: lessons
      learned in the Netherlands.
AB  - Occupational back pain remains a serious problem for nurses. In Dutch health
      care, ergonomic changes are stimulated through convenants. For acute and critical
      care, a covenant was drawn up and guidelines for nursing practice developed and
      implemented. Because of the diverse and rapidly changing nature of ergonomic
      problems, the process has to be specific. A strong emphasis thus was placed on
      self-management and empowerment of nurses. One or two nurses were appointed per
      ward as peer leaders, called ergocoaches. They received additional training and
      were given responsibility for safe work practices. This article reports on
      progress made to date, viewed as work in progress.

PMID- 17512477
TI  - Creating a culture of change through implementation of a safe patient handling
      program.
AB  - Health care professionals have a high risk for being injured while moving
      patients manually. The University of Iowa Hospitals and Clinics (UIHC) realized a
      need to reduce injuries suffered during patient movement. A UIHC
      multidisciplinary task force consulted the latest research, trialed products, and
      involved employees in selecting equipment for and implementing a safe patient
      handling program. This program resulted in a 76% reduction in lost workdays and
      an 85% reduction in workers' compensation costs. The keys to this program were
      involving employees, partnering with a key vendor, engaging change agents at the
      unit level, and applying persistence and re-education to staff.

PMID- 17512478
TI  - Handling of the bariatric patient in critical care: a case study of lessons
      learned.
AB  - Bariatric admissions across the United States (US) are increasing at an alarming
      rate. The obesity epidemic costs the US health care system $70 billion per year.
      Many bariatric surgical and medical patients are admitted to critical care units.
      The mortality risks for these patients compared with non-bariatric patients is up
      to 2:1. Managing these patients is a challenge to health care nursing personnel.
      Patient size, care required, equipment technology, availability, and
      environmental space can increase risk for injury for nursing personnel and
      patients. The Health Sciences Center in Winnipeg shares a case study of an
      admission of a 697-lb patient, reviewing lessons learned, techniques, equipment,
      and difficulties.

PMID- 17512480
TI  - Neuropathic pain in soft tissue complaints.
AB  - Many soft tissue complaints are associated with the development of neuropathic
      pain. This pain is produced by pathophysiological processes that are different to
      the processes involved in the generation of the inflammatory or nociceptive pain
      more commonly encountered in soft tissue disorders. One of the consequences of
      this is that neuropathic pain can often be less responsive to standard analgesic
      therapies. The use of alternative analgesic strategies may be necessary if we are
      to treat neuropathic pain successfully. This chapter aims to outline some of the
      clinical features associated with neuropathic pain, the aetiological factors
      leading to its development and the evidence base (or lack) behind current
      treatment strategies. It will try to provide a rational approach to the
      management of neuropathic pain in patients with soft tissue disorders,
      particularly focusing on pharmacological management. Neuropathic pain is the
      focus of much current research activity, particularly pharmacological research,
      and this chapter will attempt to identify gaps in our clinical knowledge and
      highlight opportunities for further research.

PMID- 17512481
TI  - Imaging modalities in the evaluation of soft tissue complaints.
AB  - A number of imaging modalities are available for the assessment of soft tissue
      complaints. The strengths and advantages of each modality must be seen in the
      context of any corresponding weakness or disadvantage. The sensitivity and
      specificity of the imaging technique must also be understood. In this article,
      each main radiological technique will be considered in turn. Fundamental
      technical aspects and common variations of the basic imaging theme will be
      explained and their relative strengths and limitations will be explored. Typical
      common clinical uses in the context of soft-tissue complaints will be considered.

PMID- 17512482
TI  - The assessment and management of chronic hamstring/posterior thigh pain.
AB  - Hamstring injuries have a high incidence and recurrence rate. Much is understood
      with regards to the mechanism of hamstring injury, with eccentric loading at fast
      rates being important. Little is known about the aetiology of hamstring injury,
      with age and previous injury being the only causative factors with robust
      scientific support. Clinically, it can be difficult to differentiate between a
      lesion occurring in hamstring tissue and pain that is experienced in the
      hamstrings that is referred from elsewhere. The use of specific examination
      procedures such as the slump test and the straight leg raise, supplemented with
      other sensitive and specific tests can help in the differential diagnosis. This
      chapter will explore the aetiology of chronic hamstring injury/posterior thigh
      pain, will discuss the differential diagnosis of chronic hamstring/posterior
      thigh pain, and present a model for the management of these injuries.

PMID- 17512483
TI  - Management of rotator cuff disease: specific treatment for specific disorders.
AB  - Disease of the rotator cuff is common. It is responsible for a high proportion of
      patients with shoulder pain presenting to general practice, causing work
      absenteeism and claims for sickness benefits. Rotator cuff disease (RCD) can
      often be managed in primary health care services, although some cases may require
      secondary referral. Both extrinsic and intrinsic factors to the cuff tendon are
      thought to be involved in the pathogenesis leading on to a spectrum of conditions
      ranging from sub-acromial bursitis to mechanical failure of the cuff tendon
      itself. Careful history and examination followed by pertinent investigation are
      essential to establish the correct diagnosis. The main aim of treatment is to
      improve symptoms and restore function of the affected shoulder. The majority of
      patients suffering from RCD can be managed by conservative means, but a shift in
      attitude has led to a significant number benefiting from invasive procedures
      ranging from decompression of the sub-acromial space to large, open procedures
      reconstructing the tendon itself.

PMID- 17512484
TI  - Rehabilitation of Achilles and patellar tendinopathies.
AB  - Achilles and patellar tendinopathies affect a broad range of the population and
      are difficult conditions to manage clinically. The pathology is persistent in the
      chronic tendon and can be considered to be failed healing. The exact cause of
      tendinopathy pain is unclear but may be related to changes in neurovascular
      structures. Rehabilitation for Achilles and patellar tendinopathies is based on
      an exercise programme that aims to improve muscle-tendon function and normalise
      the pelvic/lower limb kinetic chain. This incorporates a programme for restoring
      and improving muscle strength, endurance and power and retraining sport-specific
      function. Rehabilitation may take a prolonged period of time, both the athlete
      and clinician must be patient and persistent to maximise results from an exercise
      based treatment.

PMID- 17512485
TI  - Muscle injuries: optimising recovery.
AB  - Muscle injuries are one of the most common traumas occurring in sports. Despite
      their clinical importance, there are only a few clinical studies on the treatment
      of muscle injuries. Lack of clinical studies is most probably attributable to the
      fact that there is not only a high heterogeneity in the severity of injuries, but
      also the injuries take place in different muscles, making it very demanding to
      carry out clinical trials. Accordingly, the current treatment principles of
      muscle injuries have either been derived from experimental studies or been tested
      empirically only. Clinically, first aid for muscle injuries follows the RICE
      (Rest, Ice, Compression and Elevation) principle. The objective of RICE is to
      stop the injury-induced bleeding into the muscle tissue and thereby minimise the
      extent of the injury. Clinical examination should be carried out immediately
      after the injury and 5-7 days after the initial trauma, at which point the
      severity of the injury can be assessed more reliably. At that time, a more
      detailed characterisation of the injury can be made using imaging diagnostic
      modalities (ultrasound or MRI) if desired. The treatment of injured skeletal
      muscle should be carried out by immediate immobilisation of the injured muscle
      (clinically, relative immobility/avoidance of muscle contractions). However, the
      duration of immobilisation should be limited to a period sufficient to produce a
      scar of sufficient strength to bear the forces induced by remobilisation without
      re-rupture and the return to activity (mobilisation) should then be started
      gradually within the limits of pain. Early return to activity is needed to
      optimise the regeneration of healing muscle and recovery of the flexibility and
      strength of the injured skeletal muscle to pre-injury levels. The rehabilitation
      programme should be built around progressive agility and trunk stabilisation
      exercises, as these exercises seem to yield better outcome for injured skeletal
      muscle than programmes based exclusively on stretching and strengthening of the
      injured muscle.

PMID- 17512486
TI  - Injection therapies for soft-tissue lesions.
AB  - Local injection therapies, used in the management of a variety of musculoskeletal
      pain syndromes, include the local infiltration of substances such as
      corticosteroid, anaesthetic, sclerosants and botulinum toxin, as well as dry
      needling alone and neural blockade. In this chapter, a number of injection
      therapies for soft-tissue-mediated pain are described. The reasoning for their
      use, potential mechanisms of action and unwanted effects are discussed. The
      literature relating to their effects is critically reviewed. Practical
      suggestions for their utilisation in the management of soft-tissue conditions are
      given and proposals are made for future research in this important area.

PMID- 17512487
TI  - Occupational disorders: non-specific forearm pain.
AB  - Work-related upper limb disorder is a non-specific diagnosis for pain in the
      hand, wrist or, in particular, forearm once more discrete clinical conditions
      such as epicondylitis, tenosynovitis and carpal tunnel syndrome have been
      excluded. The pathophysiology of the condition is uncertain, although it is
      normally held to be related to an ergonomic incident. Ergonomic factors either at
      work or at home remain important and are discussed. Initial management is based
      on modification of ergonomics with appropriate periods of rest and job rotation.
      Treatment, however, remains somewhat unfocused and unsatisfactory. Much can be
      learnt from the ergonomic study of musicians, where the condition is perhaps at
      its most refined. Medico-legal aspects and recent thoughts on pathogenesis are
      also discussed.

PMID- 17512488
TI  - Regional myofascial pain: diagnosis and management.
AB  - This chapter defines and describes the condition that is known by the term
      myofascial trigger point pain syndrome. An outline is given of the current state
      of knowledge of the pathophysiology of myofascial trigger points, including the
      latest details from needle microdialysis in near real-time. The clinical features
      of this pain syndrome are summarised in general terms and the reliability of the
      clinical diagnosis is discussed. The clinical evidence for and against the common
      therapeutic interventions used in the management of myofascial pain is reviewed
      in detail and some tentative conclusions are reached with respect to needling
      therapies.

PMID- 17512489
TI  - Metabolic alterations in cultured mouse fibroblasts induced by an inhibitor of
      the tyrosine kinase receptor Fibroblast Growth Factor Receptor 1.
AB  - Proton nuclear magnetic resonance (NMR) spectroscopy was used to identify and
      quantify the metabolites present in cultured mouse fibroblast cells 3T6 in their
      native state and after treatment with PD166866, an inhibitor of the fibroblast
      growth factor receptor. Cell extracts were prepared according to the Bligh-Dyer
      protocol which prevents artifacts deriving from the chemical demolition of
      macromolecules. Also the growth medium was subjected to the same extraction
      procedure. The NMR approach made possible the identification and quantification
      of about 40 different metabolites at nanomoles/mg of protein level: the
      biological relevance of the variation of some metabolite levels is discussed. Our
      experimental procedure offers a prospective method for the evaluation of
      variations of the metabolic profile deriving from different biochemical
      treatments of these cells.

PMID- 17512490
TI  - Flow cytometric detection of saxitoxins using fluorescent voltage-sensitive dyes.
AB  - By virtue of their ability to block depolarization of nerve cells, the saxitoxins
      exert the toxic effects associated with paralytic shellfish poisoning and allow
      for their detection through various methodologies. When veratridine-induced
      depolarization is followed using voltage-sensitive fluorescent dyes, the presence
      of these toxic blocking agents can be observed as a decrease in fluorescence of
      dye-treated nerve cells. Detection using flow cytometry provides for selection of
      the most responsive population of cultured mouse neuroblastoma (Neuro 2a) cells
      thereby enhancing assay sensitivity and this approach can be accomplished in real
      time. The method is demonstrated in preliminary studies using saxitoxin and crude
      shellfish extracts.

PMID- 17512491
TI  - Incorporating data link messaging into a multi-function display to support the
      Small Aircraft Transportation System (SATS) and the self-separation of general
      aviation aircraft.
AB  - One objective of the Small Aircraft Transportation System (SATS) Project is to
      increase the capacity and utilization of small non-towered, non-radar equipped
      airports by transferring traffic management activities to an automated system and
      separation responsibilities to general aviation (GA) pilots. This paper describes
      the development of a research multi-function display (MFD) to support the
      interaction between pilots and an automated Airport Management Module (AMM).
      Preliminary results of simulation and flight tests indicate that adding the
      responsibility of monitoring other traffic for self-separation does not increase
      pilots' subjective workload levels. Pilots preferred using the enhanced MFD to
      execute flight procedures, reporting improved situation awareness (SA) over
      conventional instrument flight rules (IFR) procedures.

PMID- 17512492
TI  - The development of the Quick Exposure Check (QEC) for assessing exposure to risk
      factors for work-related musculoskeletal disorders.
AB  - This paper describes the development and evaluation of the Quick Exposure Check
      (QEC), which is an observational tool developed for Occupational Safety and
      Health (OSH) practitioners to assess exposure to risks for work-related
      musculoskeletal disorders and provide a basis for ergonomic interventions. The
      tool is based on epidemiological evidence and investigations of OSH
      practitioners' aptitudes for undertaking assessments. It has been tested,
      modified and validated using simulated and workplace tasks, in two phases of
      development, with participation of 206 practitioners. The QEC allows the four
      main body areas to be assessed and involves practitioners and workers in the
      assessment. Trials have determined its usability, intra- and inter-observer
      reliability, and validity which show it is applicable to a wide range of working
      activities. The tool focuses primarily on physical workplace factors, but also
      includes the evaluation of psychosocial factors. Tasks can normally be assessed
      within 10min. It has a scoring system, and exposure levels have been proposed to
      guide priorities for intervention. Subsequently it should be used to evaluate the
      effectiveness of any interventions made. The QEC can contribute to a holistic
      assessment of all the elements of a work system.

PMID- 17512494
TI  - Perceived threat: exploring its association with worry and its hypothesized
      antecedents.
AB  - Two studies with college student participants (n's=262, 239) examined the
      relation between perceptions of threat (i.e., perceptions of the probabilities
      and costs of future undesirable outcomes) and: (a) worry; and (b) hypothesized
      antecedents of perceived threat. In both studies, higher levels of worrying were
      associated with higher perceived probability and cost. In Study 2, the
      association between perceived threat and worrying remained even when taking into
      account maladaptive worry beliefs and the desire for predictability; in fact, the
      relation between worrying and worry beliefs and desire for predictability were
      moderated by perceptions of threat. Higher levels of perceived probability were
      associated with perceiving oneself and others less favorably, whereas higher
      levels of perceived cost were associated with higher standards.

PMID- 17512495
TI  - Three-dimensional nanometry of vesicle transport in living cells using dual-focus
      imaging optics.
AB  - Dual-focus imaging optics for three-dimensional tracking of individual quantum
      dots has been developed to study the molecular mechanisms of motor proteins in
      cells. The new system has a high spatial and temporal precision, 2 nm in the x-y
      sample plane and 5 nm along the z-axis at a frame time of 2 ms. Three-dimensional
      positions of the vesicles labeled with quantum dots were detected in living
      cells. Vesicles were transported on the microtubules using 8-nm steps towards the
      nucleus. The steps had fluctuation of approximately 20 nm which were
      perpendicular to the axis of the microtubule but with the constant distance from
      the microtubule. The most of perpendicular movement was not synchronized with the
      8-nm steps, indicating that dynein moved on microtubules without changing the
      protofilaments. When the vesicles changed their direction of movement toward the
      cell membrane, they moved perpendicular with the constant distance from the
      microtubule. The present method is powerful tool to investigate three dimensional
      movement of molecules in cells with nanometer and millisecond accuracy.

PMID- 17512493
TI  - New liver cell mutants defective in the endocytic pathway.
AB  - To isolate mutant liver cells defective in the endocytic pathway, a selection
      strategy using toxic ligands for two distinct membrane receptors was utilized.
      Rare survivors termed trafficking mutants (Trf2-Trf7) were stable and more
      resistant than the parental HuH-7 cells to both toxin conjugates. They differed
      from the previously isolated Trf1 HuH-7 mutant as they expressed casein kinase 2
      alpha'' (CK2alpha'') which is missing from Trf1 cells and which corrects the Trf1
      trafficking phenotype. Binding of (125)I-asialoorosomucoid (ASOR) and cell
      surface expression of asialoglycoprotein receptor (ASGPR) were reduced
      approximately 20%-60% in Trf2-Trf7 cells compared to parental HuH-7, without a
      reduction in total cellular ASGPR. Based on (125)I-transferrin binding, cell
      surface transferrin receptor activity was reduced between 13% and 88% in the
      various mutant cell lines. Distinctive phenotypic traits were identified in the
      differential resistance of Trf2-Trf7 to a panel of lectins and toxins and to UV
      light-induced cell death. By following the endocytic uptake and trafficking of
      Alexa(488)-ASOR, significant differences in endosomal fusion between parental HuH
      7 and the Trf mutants became apparent. Unlike parental HuH-7 cells in which the
      fusion of endosomes into larger vesicles was evident as early as 20 min, ASOR
      endocytosed into the Trf mutants remained within small vesicles for up to 60 min.
      Identifying the biochemical and genetic mechanisms underlying these phenotypes
      should uncover novel and unpredicted protein-protein or protein-lipid
      interactions that orchestrate specific steps in membrane protein trafficking.

PMID- 17512497
TI  - Enhancement of Natural Killer cell cytotoxicity by a CD18 integrin-activating
      antibody.
AB  - Natural Killer (NK) cells kill certain tumor cells and virus infected cells in an
      antigen-independent manner. Members of CD18 integrins such as CD11a, CD11b, and
      CD11c are expressed in all NK cells. CD18-blocking mAbs inhibit the killing
      activity of NK cells implying an essential role of these integrins in NK cell
      cytotoxicity. In this report we show that the pan CD18-activating mAb, 240Q,
      augments cytotoxicity of resting NK cells. Since activation of either CD11a or
      CD11c alone fails to augment the NK cell activity, we postulate that a functional
      synergy of the individual CD18 integrins is responsible for the observed
      stimulatory effect of pan CD18 activation on NK cell cytotoxicity.

PMID- 17512498
TI  - STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7
      cells.
AB  - Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor
      protein as a c-Fms/M-CSF receptor-interacting protein and constitutively
      expressed in macrophages. Our previous studies also revealed that STAP-2 binds to
      MyD88 and IKK-alpha/beta, and modulates NF-kappaB signaling in macrophages. In
      the present study, we examined physiological roles of the interaction between
      STAP-2 and c-Fms in Raw 264.7 macrophage cells. Our immunoprecipitation has
      revealed that c-Fms directly interacts with the PH domain of STAP-2 independently
      on M-CSF-stimulation. Ectopic expression of STAP-2 markedly suppressed M-CSF
      induced tyrosine phosphorylation of c-Fms as well as activation of Akt and
      extracellular signal regulated kinase. In addition, Raw 264.7 cells over
      expressing STAP-2 showed impaired migration in response to M-CSF and wound
      healing process. Taken together, our findings demonstrate that STAP-2 directly
      binds to c-Fms and interferes with the PI3K signaling, which leads to macrophage
      motility, in Raw 264.7 cells.

PMID- 17512499
TI  - Caenorhabditis elegans p97/CDC-48 is crucial for progression of meiosis I.
AB  - p97/VCP/Cdc48p belongs to the AAA (ATPases associated with diverse cellular
      activities) family and has been indicated to be required for mitotic M-phase. We
      previously reported that simultaneous depletion of two p97 homologues, CDC-48.1
      and CDC-48.2, in Caenorhabditis elegans caused the complete embryonic lethality,
      and that a large number of vacuole-like structures were observed in the dead
      embryos. However, cellular functions of p97 in embryogenesis have not been
      revealed. In this study, we analyzed effects of p97 depletion on meiotic
      progression. Simultaneous depletion of both p97 resulted in the formation of
      aberrant multinucleate cells and sometimes ectopic furrows in embryos.
      Importantly, meiotic chromosomes were not divided at meiotic metaphase I in p97
      depleted embryos, although spindle formation and disassembly occurred.
      Furthermore, we found that chromosome condensation was significantly reduced in
      p97-depleted oocytes. Taken these results altogether, we propose that C. elegans
      p97 plays an important role in the progression of meiosis.

PMID- 17512500
TI  - Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitro.
AB  - The retinoic acid related orphan receptor RORalpha activates transcription of
      genes that play an important role in cerebellar development, the protection
      against age-related degenerative processes, the regulation of inflammatory
      responses, and is one of the pivotal participants that control the circadian
      rhythmicity in the core-clock of mammals. We identified the extracellular signal
      regulated kinase 2 (ERK-2) as RORalpha4 phosphorylating kinase in vitro. The
      primary sequence of RORalpha4 contains an ERK-2 recognition motif (P-L-T(128)-P)
      within the hinge domain, and mutation of Thr-128 to Ala prevents RORalpha4
      phosphorylation by ERK. The RORalpha4-T128A mutant exhibits an increased DNA
      binding affinity, an increased transcriptional activity and, in the interplay
      with the opponent RevErbalpha, acts as a stronger competitor at ROR response
      elements than RORalpha4-WT.

PMID- 17512501
TI  - Estrogen-related receptor alpha modulates the expression of adipogenesis-related
      genes during adipocyte differentiation.
AB  - Estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor that
      regulates cellular energy metabolism by modulating gene expression involved in
      fatty acid oxidation and mitochondrial biogenesis in brown adipose tissue.
      However, the physiological role of ERRalpha in adipogenesis and white adipose
      tissue development has not been well studied. Here, we show that ERRalpha and
      ERRalpha-related transcriptional coactivators, peroxisome proliferator-activated
      receptor gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) and PGC-1beta, can be
      up-regulated in 3T3-L1 preadipocytes at mRNA levels under the adipogenic
      differentiation condition including the inducer of cAMP, glucocorticoid, and
      insulin. Gene knockdown by ERRalpha-specific siRNA results in mRNA down
      regulation of fatty acid binding protein 4, PPARgamma, and PGC-1alpha in 3T3-L1
      cells in the adipogenesis medium. ERRalpha and PGC-1beta mRNA expression can be
      also up-regulated in another preadipocyte lineage DFAT-D1 cells and a pluripotent
      mesenchymal cell line C3H10T1/2 under the differentiation condition. Furthermore,
      stable expression of ERRalpha in 3T3-L1 cells up-regulates adipogenic marker
      genes and promotes triglyceride accumulation during 3T3-L1 differentiation. These
      results suggest that ERRalpha may play a critical role in adipocyte
      differentiation by modulating the expression of various adipogenesis-related
      genes.

PMID- 17512502
TI  - Localization of Parkinson's disease-associated LRRK2 in normal and pathological
      human brain.
AB  - Mutations in the LRRK2 gene cause autosomal dominant, late-onset parkinsonism,
      which presents with pleomorphic pathology including alpha-synucleopathy. To
      promote our understanding of the biological role of LRRK2 in the brain we
      examined the distribution of LRRK2 mRNA and protein in postmortem human brain
      tissue from normal and neuropathological subjects. In situ hybridization and
      immunohistochemical analysis demonstrate the expression and localization of LRRK2
      to various neuronal populations in brain regions implicated in Parkinson's
      disease (PD) including the cerebral cortex, caudate-putamen and substantia nigra
      pars compacta. Immunofluorescent double labeling studies additionally reveal the
      prominent localization of LRRK2 to cholinergic-, calretinin- and GABA(B) receptor
      1-positive, dopamine-innervated, neuronal subtypes in the caudate-putamen. The
      distribution of LRRK2 in brain tissue from sporadic PD and dementia with Lewy
      bodies (DLB) subjects was also examined. In PD brains, LRRK2 immunoreactivity
      localized to nigral neuronal processes is dramatically reduced which reflects the
      disease-associated loss of dopaminergic neurons in this region. However,
      surviving nigral neurons occasionally exhibit LRRK2 immunostaining of the halo
      structure of Lewy bodies. Moreover, LRRK2 immunoreactivity is not associated with
      Lewy neurites or with cortical Lewy bodies in sporadic PD and DLB brains. These
      observations indicate that LRRK2 is not a primary component of Lewy bodies and
      does not co-localize with mature fibrillar alpha-synuclein to a significant
      extent. The localization of LRRK2 to key neuronal populations throughout the
      nigrostriatal dopaminergic pathway is consistent with the involvement of LRRK2 in
      the molecular pathogenesis of familial and sporadic parkinsonism.

PMID- 17512503
TI  - Comparison of the effects of maternal protein malnutrition and intrauterine
      growth restriction on redox state of central nervous system in offspring rats.
AB  - Both maternal protein malnutrition and intrauterine growth restriction (IUGR)
      have deleterious effects on brain development, but a comparison of these effects
      has not been previously reported. The objectives of this study were to
      investigate and compare the effects of both factors on the oxidative status of
      the central nervous system (CNS), including the spinal cord, in offspring rats.
      We evaluated various parameters of oxidative status and antioxidant enzyme
      activities of superoxide dismutase and catalase (CAT) in different regions of the
      CNS from 60-day-old rats subjected to prenatal and postnatal protein restrictions
      [middle protein restriction 12%, severe protein restriction (SPR) 4%] or IUGR
      produced by uterine artery ligation. Furthermore, we compared these study groups
      to each other and to control rats fed an isocaloric 24% protein diet. Results
      were analyzed using one-way ANOVA followed by Tukey's post hoc test. Both protein
      restrictions and IUGR altered various parameters of oxidative status. In all
      evaluated structures, protein restrictions resulted in increases in
      thiobarbituric acid-reactive substances level and index of lipid peroxidation
      (P<0.001), and in decreases in antioxidant enzyme activities (P<0.005). IUGR also
      increased lipid peroxidation levels in the blood samples (P<0.04) and protein
      oxidative damage in the cerebellum and cerebral cortex (P<0.005); however, no
      effects were detected on the spinal cord. The greatest decrease in CAT activity
      was in the cerebellum of rats fed with SPR diet (P<0.001). This study suggests
      that not only severe but also middle protein malnutrition have deleterious
      effects on CNS structures, including the spinal cord. Protein restriction has a
      greater effect on the redox state of the CNS than IUGR.

PMID- 17512504
TI  - Dilated cardiomyopathy is associated with reduced expression of the cardiac
      sodium channel Scn5a.
AB  - OBJECTIVE: Dilated cardiomyopathy (DCM) leads to dilation of the cardiac chambers
      and congestive heart failure. Recent reports have associated mutations in the
      SCN5A gene, which codes for the major cardiac sodium channel Nav1.5, with DCM.
      Although DCM is the most common form of cardiomyopathy, no animal studies have
      established this functional connection. METHODS AND RESULTS: We have produced
      transgenic mice that ectopically express the transcriptional repressor Snail in
      heart. These animals display severe DCM, ECG abnormalities, conduction defects,
      revealed by voltage-sensitive dye imaging, and significantly reduced voltage
      gated sodium current as measured by patch clamping. There is a concomitant
      decrease in expression of the major cardiac sodium channel gene Scn5a, which we
      show by gene reporter assays and electrophoretic mobility shift assays is a
      direct target of Snail. CONCLUSIONS: Our findings indicate that a decrease in
      Scn5a expression and significant reduction in sodium current can result in DCM,
      and support the hypothesis that some mutations in the human SCN5A gene can lead
      to DCM.

PMID- 17512505
TI  - Role of rat alpha adducin in angiogenesis: null effect of the F316Y polymorphism.
AB  - OBJECTIVE: Rat alpha adducin point mutation (F316Y) has been associated with
      primary systemic arterial hypertension. As microcirculatory abnormalities are
      present in most forms of hypertension, the aim of the present study was to
      investigate whether rat alpha adducin may regulate endothelial cell (EC)
      functions in vitro and in vivo. METHODS AND RESULTS: The overexpression of rat
      wild type alpha adducin (WT-Add1) in ECs induced capillary-like structure
      development in Matrigel in vitro and enhanced capillary formation in Matrigel
      implants in vivo in CD1 mice. In contrast, the overexpression of the mutated form
      (MUT-Add1) of rat alpha adducin had a Null effect in vitro and lacked any
      significant activity in vivo. Further, adenovirus-mediated rat WT-Add1 but not
      MUT-Add1 gene transfer to murine ischemic hindlimb enhanced capillary formation
      in skeletal muscles. Gene profiling of human umbilical vein endothelial cells
      overexpressing alpha adducin was performed in order to identify putative effector
      molecules of alpha adducin-mediated activities on ECs. Interestingly, among a
      number of genes involved in angiogenesis regulation, retinoic acid-induced
      protein (RAI17) was found to be upregulated in WT-Add1 vs MUT-Add1 overexpressing
      cells, possibly representing a key molecule/axis for the functional Add1-induced
      effect. CONCLUSIONS: Rat WT alpha adducin enhanced EC functions both in vitro and
      in vivo. The expression of the F316Y variant, associated with the hypertensive
      phenotype, had a Null effect and might contribute to endothelial
      rarefaction/dysfunction in hypertension. RAI17 was found to be a putative
      effector molecule differentially regulated by the overexpression of the two forms
      of Add1 in endothelial cells.

PMID- 17512506
TI  - NO metabolite flux across the human coronary circulation.
AB  - OBJECTIVES: The theory of a red blood cell derived nitric oxide (NO) reserve
      conserving NO bioactivity and delivering NO as a function of oxygen demand has
      been the subject of much interest. We identified the human coronary circulation
      as an ideal model system in which to analyse NO metabolites because of its large
      physiological oxygen gradient. Our objective was to identify whether oxygen drove
      apportion between various NO metabolite species across a single vascular bed.
      METHODS: Plasma and red blood cell NO metabolites were assessed from the left
      main coronary artery, coronary sinus and pulmonary artery (providing cross heart
      and cross pulmonary analysis) of healthy subjects under resting conditions and
      following administration of an inhibitor of NO biosynthesis. Physiological
      parameters and angiographic data were monitored throughout the study. RESULTS:
      Under baseline conditions we observed significant metabolite flux upon the
      transit of blood across the coronary and pulmonary vascular beds. Whilst there
      was no net loss of NO through the coronary circulation (p=0.0759), plasma
      nitrite/protein NO (excluding nitrate) (p=0.0279) and red blood cell
      sulphanilamide labile signal (p=0.0143) decreased whereas haemoglobin-bound NO
      increased three-fold (p=0.005). These changes across the coronary circulation
      were reversed through the pulmonary circuit with red blood cell sulphanilamide
      labile signal (p=0.0143) and plasma nitrite/protein NO (p=0.0279) increasing and
      haemoglobin-bound NO decreasing. Blockade of NO synthesis increased mean arterial
      blood pressure (p<0.01) and reduced coronary artery diameter (p<0.05), however we
      observed similar apportion of NO metabolites across the heart and lung with no
      net loss or gain in total NO metabolites. CONCLUSIONS: For the first time in
      human subjects across the resting coronary circulation we reveal significant re
      apportionment of NO between metabolite species which correlate with haemoglobin
      oxygen saturation. These changes occur even within the transit time of blood
      across this single vascular bed. We demonstrate no net loss/gain of NO from the
      total metabolite pool across the coronary circulation even where NO biosynthesis
      is inhibited.

PMID- 17512507
TI  - Preconditioning and postconditioning: the essential role of the mitochondrial
      permeability transition pore.
AB  - OBJECTIVE: The opening of the mitochondrial permeability transition pore (mPTP)
      at the time of myocardial reperfusion is a critical determinant of cell death.
      Emerging studies suggest that suppression of mPTP opening may underlie the
      cardioprotection elicited by both ischemic preconditioning (IPC) and
      postconditioning (IPost). To further evaluate the role of the mPTP in
      cardioprotection, we hypothesized that hearts deficient in cyclophilin-D (CYP-D-/
      ), a key component of the mPTP, will be resistant to cardioprotection conferred
      by ischemic and pharmacological preconditioning and postconditioning. METHODS AND
      RESULTS: Male/female wild type or CYP-D-/- mice were subjected to 30 min of
      ischemia and 120 min of reperfusion. In wild type mice subjected to in vivo
      myocardial ischemia-reperfusion injury, a significant reduction in myocardial
      infarct size was observed with the following treatments (n>/=6/group; P<0.05):
      (1) IPC (28+/-4% vs. 46.2+/-4% in control); (2) Diazoxide (5 mg/kg) pre-treatment
      (26.4+/-3% vs. 54+/-10% in vehicle control); (3) IPost-1 or IPost-2, three or six
      10-s cycles of ischemia-reperfusion (27.2+/-3% and 32+/-4%, respectively vs.
      46.2+/-4% in control); (4) Bradykinin (40 mug/kg) (28.3+/-1% vs. 48+/-4% in
      vehicle control); (5) cyclosporin-A (10 mg/kg) (32.3+/-3% vs. 48+/-4% in vehicle
      control) (6) sanglifehrin-A (25 mg/kg) (29.3+/-3% vs. 48+/-4% in vehicle
      control). Interestingly, however, no infarct-limiting effects were demonstrated
      in CYP-D-/- mice with the same treatment protocols: (27.9+/-5% in control vs.
      31.2+/-7% with IPC, 30.2+/-5% with IPost-1, 24.7+/-8% with IPost-2; 30.1+/-4% in
      vehicle control vs. 26.4+/-7% with diazoxide; 24.6+/-4% in vehicle control vs.
      24.9+/-5% with bradykinin, 26.8+/-7% with cyclosporin-A, 32.5+/-6% with
      sanglifehrin-A: n>/=6/group: P>0.05). CONCLUSION: This study demonstrates that
      the mPTP plays a critical role in the cardioprotection elicited by ischemic and
      pharmacological preconditioning and postconditioning.

PMID- 17512508
TI  - An in vitro investigation of the induction of apoptosis and modulation of cell
      cycle events in human cancer cells by bisphenanthroline-coumarin-6,7
      dioxacetatocopper(II) complex.
AB  - The central objective of the current study was to investigate the potential in
      vitro anti-proliferative properties of the parent ligand, coumarin-dioxy-acetic
      acid (cdoaH(2)), and its copper complex, copper-coumarin-dioxyacetic acetate
      phenathroline ([Cu(cdoa)(phen)(2)]) using four human-derived model cell lines,
      two neoplastic and two non-neoplastic. In addition, selected mechanistic studies
      were carried out using one of the neoplastic-derived model cell lines, Hep-G2.
      Results obtained show that the complex, rather than the ligand, could alter the
      proliferation of both human neoplastic renal (A-498) and hepatic (Hep-G2) cells.
      Furthermore, hepatic non-neoplastic cells (Chang) appeared to be less sensitive.
      However, this effect was not mirrored in non-neoplastic renal (HK-2) cells, a
      profile shared with cisplatin. The observed anti-proliferative effect appeared to
      be concentration- and time-dependant, and could be attributed to the complex,
      rather than any of the component parts, i.e. 1,10-phenanthroline, the coumarin
      ligand, or the simple metal salt. Furthermore, the complex was shown to decrease
      DNA synthesis, but did not intercalate with it. Based on IC(50) values,
      [Cu(cdoa)(phen)(2)] was shown to be almost six times more potent than cisplatin.
      Moreover, there was no evidence to show that P-glycoprotein (P-gp)-mediated multi
      drug resistance (MDR) was likely to play a role in decreasing the anti
      proliferative activity of the complex. Cytological stains, analysis of genomic
      DNA, and biochemical assays [caspase-3 and -9 and cleaved poly(ADP-ribose)
      polymerase protein], suggested that cell death could switch between apoptosis and
      necrosis, and this effect appeared to be concentration-dependent. Additionally,
      flow cytometric analysis showed that the complex functioned through an alteration
      in cell cycle progression. Taken together, [Cu(cdoa)(phen)(2)] has been shown to
      be a more potent anti-proliferative agent than either the ligand or cisplatin,
      and is capable of altering key biochemical events leading to the execution of
      apoptotic and/or necrotic cell death, suggesting that it is worthy of further
      investigation.

PMID- 17512509
TI  - The -429 T>C polymorphism of the receptor for advanced glycation end products
      (RAGE) is associated with type 1 diabetes in a Brazilian population.

PMID- 17512510
TI  - Saliva specimen: a new laboratory tool for diagnostic and basic investigation.
AB  - The assay of saliva is an increasing area of research with implications for basic
      and clinical purposes. Although this biological fluid is easy to manipulate and
      collect, careful attention must be directed to limit variation in specimen
      integrity. Recently, the use of saliva has provided a substantial addition to the
      diagnostic armamentarium as an investigative tool for disease processes and
      disorders. In addition to its oral indications, the analysis of saliva provides
      important information about the functioning of various organs within the body. In
      this respect, endocrine research certainly occupies a central role. The present
      review considers the laboratory aspects of salivary assays with respect to the
      different analytes including ions, drugs and various non-protein/protein
      compounds such as hormones and immunoglobulins. This review also examines the
      consequences of preanalytical variation with respect to collection strategy and
      subsequent storage conditions. It is likely that the use of saliva in assays will
      continue to expand thus providing a new instrument of investigation for
      physiologic as well as pathophysiologic states.

PMID- 17512511
TI  - Investigation of release and degradation of cardiac troponin T in patients with
      acute myocardial infarction.
AB  - OBJECTIVES: Cardiac troponin T (cTnT) degradation after tissue release is still
      under debate. Because degradation of cTnT might have consequences on clearance of
      the molecule from the circulation, but also on the assay performance, the aim of
      this study was to investigate cTnT release and degradation in serum of AMI
      patients. DESIGN AND METHODS: Serum samples were collected from 20 patients with
      AMI diagnosis undergoing rapid revascularization. Intact cTnT and fragments were
      detected using a combination of immunoprecipitation, SDS-PAGE and Western
      blotting. RESULTS: The intact cTnT protein was detected only during the first 12
      h after the cTnT concentration started to increase above the AMI cut-off value of
      0.03 microg/L. Thereafter only fragments with molecular weights ranging from 10
      to 30 kDa were detected, with two fragments being most prominent (15 and 25 kDa).
      CONCLUSIONS: Intact cTnT rapidly disappears from the circulation during the early
      hours after AMI, but immunoreactive fragments remain present longer. The current
      cTnT immunoassay detects both intact cTnT and fragments.

PMID- 17512512
TI  - Comparative study of some physico-chemical characteristics of osteoporotic and
      normal human femur heads.
AB  - OBJECTIVE: To compare some of the physico-chemical properties of osteoporotic and
      normal femur heads -- a sample study. MATERIALS AND METHODS: The organic and
      inorganic parts of human normal (healthy) (N), osteoporotic (OP) femur heads and
      were separated using conventional methods and their physico-chemical
      characteristics were compared using infrared spectroscopy (IR), thermogravimetric
      analysis (TGA), X-ray diffraction (XRD) and scanning electron microscopy (SEM).
      RESULTS: The data revealed that the extra crosslinking had taken place between
      the intramolecular alpha chains of collagen of OP bone. This was confirmed by IR
      spectroscopy and TGA studies. XRD data of the inorganic part of N have shown well
      resolved peaks compared to OP revealing the decreased crystallinity in the
      osteoporotic bone. CONCLUSIONS: The extra intramolecular crosslinking of OP bone
      collagen molecules increases its fragility. The crystallinity of inorganic phase
      is less in OP and this may be the reason for its brittleness.

PMID- 17512513
TI  - The inflammation-sensitive protein alpha 1-anti-chymotrypsin neutralizes
      fibrillar aggregation and cytotoxicity of the beta-amyloid peptide more
      effectively than alpha 1-antitrypsin.
AB  - OBJECTIVES: A neuroinflammatory process, triggered by amyloid-beta (Abeta)
      peptide, is thought to play a central role in the neurodegenerative process
      leading to Alzheimer's disease (AD). Abeta(25-35) retains the functionality of
      Abeta(42) and was employed to investigate the effects of inflammation-sensitive
      proteins (ISPs) alpha1-antichymotrypsin (A1ACT) and alpha1-antitrypsin (A1AT) on
      fibrillar aggregation and cytotoxicity. DESIGN AND METHODS: Inhibitory
      concentrations of the ISPs were determined in an established human red blood cell
      lysis model of Abeta-cytotoxicity. For studies of Abeta-fibrillar aggregation CSF
      levels of A1ACT (0.041 microM)/A1AT (0.11 microM) were incubated with Congo Red
      dye 25 microM+Abeta(25-35) 10 microM noting the formation of visible aggregates
      and spectrophotometric changes over 24 h. RESULTS: A1ACT at CSF reported levels
      inhibited fibrillar aggregation and cytotoxicity while A1AT at CSF reported
      levels failed to cause a similar inhibition. CONCLUSIONS: A1ACT neutralizes
      fibrillar aggregation and cytotoxicity of Abeta-peptide more effectively than
      A1AT. Both proteins are known to be co-deposited with Abeta within senile plaques
      of AD brains.

PMID- 17512514
TI  - Use of an interferon-gamma based assay to assess bladder cancer patients treated
      with intravesical BCG and exposed to tuberculosis.
AB  - OBJECTIVE: Compare the QuantiFERON-TB Gold In-Tube (QFT) assay and the tuberculin
      skin test (TST) in bladder cancer patients receiving high dose BCG therapy (BCG
      patients). DESIGN AND METHODS: BCG patients and healthy visitors, both exposed to
      tuberculosis, were screened with a TST and QFT. RESULTS: QFT-TST correlation was
      excellent in visitors, but poor in BCG patients. BCG therapy predicted a positive
      TST (p<0.001) but not a positive QFT (p=0.35). DISCUSSION: The management of BCG
      patients was impacted, by measuring the QFT.

PMID- 17512515
TI  - Labels can override perceptual categories in early infancy.
AB  - An extensive body of research claims that labels facilitate categorisation,
      highlight the commonalities between objects and act as invitations to form
      categories for young infants before their first birthday. While this may indeed
      be a reasonable claim, we argue that it is not justified by the experiments
      described in the research. We report on a series of experiments that demonstrate
      that labels can play a causal role in category formation during infancy. Ten
      month-old infants were taught to group computer-displayed, novel cartoon drawings
      into two categories under tightly controlled experimental conditions. Infants
      were given the opportunity to learn the two categories under four conditions:
      Without any labels, with two labels that correlated with category membership,
      with two labels assigned randomly to objects, and with one label assigned to all
      objects. Category formation was assessed identically in all conditions using a
      novelty preference procedure conducted in the absence of any labels. The
      labelling condition had a decisive impact on the way infants formed categories:
      When two labels correlated with the visual category information, infants learned
      two categories, just as if there had been no labels presented. However,
      uncorrelated labels completely disrupted the formation of any categories.
      Finally, consistent use of a single label across objects led infants to learn one
      broad category that included all the objects. These findings demonstrate that
      even before infants start to produce their first words, the labels they hear can
      override the manner in which they categorise objects.

PMID- 17512516
TI  - Numeric comparison in a visually-guided manual reaching task.
AB  - Nearly all studies on perception and cognition have used discrete responses to
      infer internal cognitive processes. In the current study, we demonstrate that
      visually-guided manual reaching can provide new opportunities to access internal
      processes over time. In each trial, participants were required to compare a
      single digit Arabic number presented on the center square with the standard, 5.
      Participants were asked to reach and touch one of three squares on the screen
      with their index finger while their hand movement trajectories were recorded: the
      left square for 1-4, the center for 5, and the right for 6-9. Direct evidence for
      an analogue representation of numbers was found in early as well as in later
      portions of hand trajectories, showing systematic shifts in position for small
      differences in numerical magnitude.

PMID- 17512517
TI  - The EGFR ligands Spitz and Keren act cooperatively in the Drosophila eye.
AB  - The EGFR signalling cascade is responsible for coordinating a wide variety of
      events during Drosophila eye development. It remains something of a mystery how
      it is that cells are able to interpret the signal so as to choose the appropriate
      response from the battery of possibilities: division, differentiation, cell shape
      change and so on. Since the cascade is essentially linear below the receptor,
      different cellular responses cannot be regulated by alternative signal
      transduction pathways. The main diversity lies upstream, in the multiple
      activating ligands. Spitz, Gurken and Vein have been long studied, but little is
      known about the physiological functions of the fourth ligand, Keren, although
      various roles have been predicted based on the differences between mutants in the
      known ligands and those of the receptor. Here, we have isolated a mutant in the
      keren gene, and demonstrate that Keren does indeed participate in EGFR signalling
      in the eye, where it acts redundantly with Spitz to control R8 spacing, cell
      clustering and survival. Thus, specificity cannot be determined by ligand choice,
      and must instead be a consequence of cell-intrinsic factors, although we
      speculate that there may be some quantitative differences in signalling elicited
      by the two ligands.

PMID- 17512519
TI  - Lead contents in the surface enamel of deciduous teeth sampled in vivo from
      children in uncontaminated and in lead-contaminated areas.
AB  - This study aimed to: (1) measure lead contents in the surface enamel of two
      populations consisting of 4-6-year-old children, one from an apparently
      uncontaminated area (Ribeirao Preto, Sao Paulo State, SP, Brazil, n=247) and the
      other from an area notoriously contaminated with lead (Bauru, Sao Paulo State,
      Brazil, n=26); (2) compare biopsy depths between the two populations; (3)
      correlate biopsy depth with lead content; (4) stratify samples according to
      biopsy depth to compare lead contents in samples from similar biopsy depths. A
      surface enamel acid-etch microbiopsy was performed in vivo on a single upper
      deciduous incisor for each sample. Lead was measured by graphite furnace atomic
      absorption spectrometry (GFAAS) while phosphorus was measured colorimetrically to
      establish biopsy depth. Samples from both populations were classified into
      categories of similar biopsy depths based on biopsy depth quartiles. Median lead
      contents were statistically different between the Ribeirao Preto population (206
      microg/g, range: 5-1399 microg/g) and the Bauru population (786 microg/g, range:
      320-4711 microg/g) (p<0.001); however, biopsy depth did not differ between the
      Ribeirao Preto (3.9 microm, Standard Deviation, SD=0.9) and Bauru (3.8 microm,
      SD=0.9) populations (p=0.7940). Pearson's correlation coefficient for biopsy
      depths versus log10 lead values was -0.29 for Ribeirao Preto and -0.18 for Bauru.
      Lead contents were statistically different between the two populations for all
      quartiles of biopsy depth. These findings suggest that lead accumulated in the
      surface enamel of deciduous teeth is linked to the environment in which people
      reside, indicating that this tissue should be further explored as an accessible
      biomarker of lead exposure.

PMID- 17512518
TI  - 18 wheeler regulates apical constriction of salivary gland cells via the Rho
      GTPase-signaling pathway.
AB  - Rho GTPase and its upstream activator, guanine nucleotide exchange factor 2
      (RhoGEF2), have emerged as key regulators of actin rearrangements during
      epithelial folding and invagination (Nikolaidou, K.K., Barrett, K. (2004). A Rho
      GTPase-signaling pathway is used reiteratively in epithelial folding and
      potentially selects the outcome of Rho activation. Curr. Biol. 14, 1822-1826).
      Here, we show that Drosophila 18 wheeler (18W), a Toll-like receptor protein, is
      a novel component of the Rho-signaling pathway involved in epithelial
      morphogenesis. 18w Mutant embryos have salivary gland invagination defects
      similar to embryos that lack components of the Rho pathway, and ubiquitous
      expression of 18W results in an upregulation of Rho signaling. Transheterozygous
      genetic interactions and double mutant analysis suggest that 18W affects the Rho
      GTPase-signaling pathway not through Fog and RhoGEF2, but rather by inhibiting
      Rho GTPase activating proteins (RhoGAPs). We show that RhoGAP5A and
      RhoGAP88C/Crossveinless-c (CV-C) are required for proper salivary gland
      morphogenesis, implicating them as potential targets of 18W.

PMID- 17512520
TI  - Neuroprotective effect of catalpol against MPP(+)-induced oxidative stress in
      mesencephalic neurons.
AB  - The neuroprotective effects of catalpol, an iridoid glycoside present in the
      roots of Rehmannia glutinosa, on 1-methyl-4-phenylpyridinium (MPP(+))-induced
      oxidative stress in cultured mesencephalic neurons, especially dopaminergic
      neurons, were investigated. Exposure of mesencephalic neurons to 10microM MPP(+)
      induced a leakage of lactate dehydrogenase (LDH) and decreased cell viability,
      measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay. Catalpol increased neuron viability and markedly attenuated MPP(+)
      induced dopaminergic neuron death in a dose-dependent manner. In order to clarify
      the neuroprotective mechanism of catalpol, mitochondrial function, the activities
      of endogenous antioxidants and the lipid peroxide content were measured. The
      results indicated that catalpol prevented the MPP(+)-induced inhibition of
      complex I activity and the loss of mitochondrial membrane potential. In addition,
      catalpol reduced the content of lipid peroxide and increased the activity of
      glutathione peroxidase and superoxide dismutase. Taken together, the above
      results suggest that catalpol may be a candidate drug for the treatment of
      oxidative stress-induced neurodegenerative disease.

PMID- 17512521
TI  - Inhibition of matrix metalloproteinase-9 activity by lisinopril after myocardial
      infarction in hamsters.
AB  - We measured angiotensin-converting enzyme and matrix metalloproteinase-9
      activities after myocardial infarction in hamsters and compared the effects of an
      angiotensin-converting enzyme inhibitor lisinopril with those of an angiotensin
      receptor blocker candesartan cilexetil after myocardial infarction. Angiotensin
      converting enzyme activity was significantly increased 3 and 7 days, but not 1
      day after myocardial infarction. Matrix metalloproteinase-9 activity was
      significantly increased 1 day after myocardial infarction. Lisinopril
      significantly inhibited both angiotensin-converting enzyme and matrix
      metalloproteinase-9 activities, but candesartan cilexetil did not. Angiotensin
      converting enzyme inhibitors might directly inhibit matrix metalloproteinase-9
      activity.

PMID- 17512522
TI  - Inhibition of human equilibrative nucleoside transporters by dihydropyridine-type
      calcium channel antagonists.
AB  - Dihydropyridine-type calcium channel antagonists, in addition to having a
      vasodilatory effect, are known to inhibit cellular uptake of nucleosides such as
      adenosine. However, the nucleoside transporter subtypes involved and the
      mechanism by which this occurs are not known. Therefore, we have studied the
      inhibitory effects of dihydropyridines on both human equilibrative nucleoside
      transporters, hENT-1 and hENT-2, which are the major transporters mediating
      nucleoside transport in most tissues. Among the dihydropyridines tested,
      nimodipine proved to be the most potent inhibitor of hENT-1, with an IC(50) value
      of 60+/-31 muM, whereas nifedipine, nicardipine, nitrendipine, and felodipine
      exhibited 100-fold less effective inhibitory activity. Nifedipine, nitrendipine,
      and nimodipine inhibited hENT-2 with IC(50) values in the micromolar range;
      however, nicardipine and felodipine had no significant effect on hENT-2. Removal
      of the 4-aryl ring or changing the nitro group at the 4-aryl ring proved not to
      be detrimental to the inhibitory effects of dihydropyridines on hENT-1, but
      resulted in a drastic decrease in their inhibitory effects on hENT-2. Kinetic
      studies revealed that nimodipine and nifedipine reduced V(max) of [(3)H]uridine
      transport without affecting K(m). The inhibitory effects of nimodipine and
      nifedipine could be washed out. In addition, nimodipine and nifedipine inhibited
      the rate of NBTGR-induced dissociation of [(3)H]NBMPR from hENT-1 cell membrane.
      We conclude that dihydropyridines are non-competitive inhibitors of hENT-1 and
      hENT-2, probably working through reversible interactions with the allosteric
      sites. The inhibitory potencies of dihydropyridines may be associated with the
      structure of the 4-aryl ring, as well as the ester groups at the C-3 and C-5
      positions.

PMID- 17512523
TI  - Parkin interacts with LIM Kinase 1 and reduces its cofilin-phosphorylation
      activity via ubiquitination.
AB  - Mutations in the PARKIN (PARK2) gene have been found in the majority of early
      onset familial Parkinson's disease (PD) patients with autosomal recessive
      juvenile parkinsonism (ARJP). Parkin protein functions as an ubiquitin (E3)
      ligase that targets specific proteins for degradation in the 26S proteasome.
      Here, based on a mass spectrometry analysis of the human dopaminergic
      neuroblastoma-derived cell line SH-SY5Y that over-expresses parkin, we found that
      parkin may suppress cofilin phosphorylation. LIM Kinase 1 (LIMK1) is the upstream
      protein that phosphorylates cofilin, an actin depolymerizing protein. Thus, we
      postulated a possible connection between parkin and LIMK1. Our studies in other
      cell lines, using co-transfection assays, demonstrated that LIMK1 and parkin bind
      each other. LIMK1 also interacted with previously known parkin interactors Hsp70
      and CHIP. Parkin enhanced LIMK1-ubiquitination in the human neuroblastoma-derived
      BE(2)-M17 cell line, but not in the human embryonic kidney-derived HEK293 cell
      line. In fact, parkin-over-expression reduced the level of LIMK1-induced
      phosphocofilin in the BE(2)-M17 cells but not in the HEK293 cells. Additionally,
      in simian kidney-derived COS-7 cells, parkin-over-expression reduced LIMK1
      induced actin filament accumulation. LIMK1 in cultured cells regulates parkin
      reversibly: LIMK1 did not phosphorylate parkin but LIMK1 overexpression reduced
      parkin self-ubiquitination in vitro and in HEK293 cells. Furthermore, in the
      cells co-transfected with parkin and p38, LIMK1 significantly decreased p38
      ubiquitination by parkin. These findings demonstrate a cell-type dependent
      functional interaction between parkin and LIMK1 and provide new evidence that
      links parkin and LIMK1 in the pathogenesis of familial PD.

PMID- 17512524
TI  - P-Glycoprotein is not present in mitochondrial membranes.
AB  - Recent reports have indicated the presence of P-glycoprotein in crude
      mitochondrial membrane fractions, leading to the assumption that P-glycoprotein
      is present in mitochondrial membranes, and may be involved in transport across
      these membranes. To determine the validity of this claim, two cell lines
      overexpressing endogenous P-glycoprotein were investigated. Using various
      centrifugation steps, mitochondria were purified from these cells and analyzed by
      Western blot reaction with the anti-P-glycoprotein antibody C219 and organelle
      specific antibodies. While P-glycoprotein is present in crude mitochondrial
      fractions, these fractions are contaminated with plasma membranes. Further
      purification of the mitochondria to remove plasma membranes revealed that P
      glycoprotein is not expressed in mitochondria of the KB-V1 (vinblastine-resistant
      KB-3-1 cells) or MCF-7(ADR) (adriamycin-resistant MCF-7 cells) cell lines. To
      further substantiate these findings, we used confocal microscopy and the anti-P
      glycoprotein antibody 17F9. This demonstrated that in intact cells, P
      glycoprotein is not present in mitochondria and is primarily localized to the
      plasma membrane. These findings are consistent with the role of P-glycoprotein in
      conferring multidrug resistance by decreasing cellular drug accumulation.
      Therefore, contrary to previous speculation, P-glycoprotein does not confer
      cellular protection by residing in mitochondrial membranes.

PMID- 17512525
TI  - Phosphorylation of human microtubule-associated protein tau by protein kinases of
      the AGC subfamily.
AB  - Intraneuronal inclusions made of hyperphosphorylated microtubule-associated
      protein tau are a defining neuropathological characteristic of Alzheimer's
      disease, and of several other neurodegenerative disorders. Many phosphorylation
      sites in tau are S/TP sites that flank the microtubule-binding repeats. Others
      are KXGS motifs in the repeats. One site upstream of the repeats lies in a
      consensus sequence for AGC kinases. This site (S214) is believed to play an
      important role in the events leading from normal, soluble to filamentous,
      insoluble tau. Here, we show that all AGC kinases tested phosphorylated S214.
      RSK1 and p70 S6 kinase also phosphorylated the neighbouring T212, a TP site that
      conforms weakly to the AGC kinase consensus sequence. MSK1 phosphorylated S214,
      as well as S262, a KXGS site in the first repeat, and S305 in the second repeat.

PMID- 17512526
TI  - Elevated plasma testosterone concentrations during stallion-like sexual behavior
      in mares (Equus caballus).
AB  - Mounting interactions in mares isolated from stallions and the relationship to
      stage of the estrous cycle and level of circulating hormones were studied for 3
      years in a herd averaging 105 mares. Mares were assigned to mounting, standing,
      and control groups. A control mare was selected by being within 1 day of the
      number of days after ovulation in a mounting mare. A total of 15 mounting
      interactions were detected by chance observation during the 3 years. A blood
      sample was collected immediately after the mounting interaction from each mare in
      the three groups, and a transrectal ultrasonographic examination of the
      reproductive tract was done. Two mounting interactions occurred during the early
      luteal phase and 13 during the follicular phase. The interactions that occurred
      during the follicular phase were used for comparisons among groups. The interval
      between mounting and the next ovulation, diameter of the two largest follicles,
      and the number of follicles larger and smaller than 20 mm were not different
      significantly among the mounting, standing, and control groups. Testosterone
      concentrations were higher (P<0.01) in the mounting group (17.7+/-2.3 pg/ml) than
      in standing group (10.9+/-0.5 pg/ml), and the difference between the mounting
      group and the control group (12.8+/-0.6 pg/ml) approached significance (P<0.08).
      Concentrations of androstenedione, estradiol, estrone, and progesterone did not
      differ significantly among groups. Results indicated that mounting behavior
      between mares is rare, usually occurs during the follicular phase, and is related
      to high circulating concentrations of testosterone.

PMID- 17512527
TI  - Effects of a breastfeeding empowerment programme on Korean breastfeeding mothers:
      a quasi-experimental study.
AB  - OBJECTIVES: This quasi-experimental study examined the effects of a new
      breastfeeding empowerment programme provided to post-partum mothers within 3 days
      of entering post-partum care centres on their breastfeeding empowerment, problems
      and practice rate. METHOD: The study employed a non-equivalent control group non
      synchronized design. Participants who conformed with the selection criteria were
      selected from two post-partum care centres affiliated with hospitals in a city in
      South Korea. Each of the two study groups included 30 participants. The
      breastfeeding empowerment programme comprised four 60-minute sessions, and was
      applied for 4 weeks to mothers in the experimental group. RESULTS: The
      breastfeeding empowerment scores were higher in the experimental group than in
      the control group (p=0.007), and there were fewer breastfeeding problems in the
      former group (p=0.012) and the breastfeeding rates were higher in the former
      group (p=0.017, 0.002 and 0.002 at 4, 8 and 12 weeks post-partum, respectively).
      CONCLUSIONS: These results indicate that the provision of breastfeeding
      empowerment programmes to help mothers to identify and solve problems by
      themselves can improve breastfeeding empowerment, problem and practice rates, and
      hence should be considered useful as a post-partum nursing intervention in
      clinical settings. The effectiveness of the various components of the
      breastfeeding empowerment programme developed in this study should be verified in
      field trials.

PMID- 17512528
TI  - Immunisation with a major Trypanosoma cruzi antigen promotes pro-inflammatory
      cytokines, nitric oxide production and increases TLR2 expression.
AB  - Innate and adaptive immunity collaborate in the protection of intracellular
      pathogens including Trypanosoma cruzi infection. However, the parasite molecules
      that regulate the host immune response have not been fully identified. We
      previously demonstrated that the immunisation of C57BL/6 mice with cruzipain, an
      immunogenic T. cruzi glycoprotein, induced a strong specific T-cell response. In
      this study, we demonstrated that active immunisation with cruzipain was able to
      stimulate nitric oxide (NO) production by splenocytes. Immune cells also showed
      increased inducible nitric oxide synthase protein and mRNA expression. Spleen
      adherent cells secreted high levels of IFN-gamma and IL-12. Microbicidal activity
      in vitro was mainly mediated by reactive nitrogen intermediaries and IFN-gamma,
      as demonstrated by the inhibitory effects of NO synthase inhibitor or by IFN
      gamma neutralisation. Specific T-cells were essential for NO, IFN-gamma and TNF
      alpha production. Furthermore, we reported that cruzipain enhanced CD80 and major
      histocompatibility complex-II molecule surface expression on F4/80+ spleen cells.
      Interestingly, we also showed that cruzipain up-regulated toll like receptor-2
      expression, not only in F4/80+ but also in total spleen cells which may be
      involved in the effector immune response. Our findings suggest that a single
      parasite antigen such as cruzipain, through adaptive immune cells and cytokines,
      can modulate the macrophage response not only as antigen presenting cells, but
      also as effector cells displaying enhanced microbicidal activity with reactive
      nitrogen intermediary participation. This may represent a mechanism that
      contributes to the immunoregulatory process during Chagas disease.

PMID- 17512529
TI  - A model for passive elastic properties of rat vena cava.
AB  - A two-dimensional model for the elastic properties of vena cava abdominalis under
      orthotropic deformation is introduced and tested against the experimental data
      obtained from six specimen of rat venae cavae by pressurization experiments. The
      model is based on membrane approximation and suited for vessels where most of the
      elastic elements are oriented axially, while circumferential contraction is
      exerted by redirecting axial stress by some network of oblique fibers. For the
      experimental data considered in this paper, the ratio between axial and
      circumferential stress depends almost exclusively on the circumferential
      extension ratio. As a consequence, the mechanical system can be formally
      decomposed in a kinematic system reacting by axial contraction on circumferential
      extension without any loss or storage of energy, serially connected to a
      hyperelastic system acting only in axial direction. Both systems are modeled
      separately by equations obtained by a purely phenomenological approach with two
      parameters for each system. This leads to reasonable reproduction of the
      experimental data. Introducing a correction parameter, which takes into account
      that the model assumption on the decomposition does not hold exactly, we get
      better reproduction of data. However, this is paid for by loss of physical rigor
      and in particular by departing from the assumption of hyperelasticity.

PMID- 17512530
TI  - Extracellular NO signalling from a mechanically stimulated osteocyte.
AB  - Bone remodelling is a dynamic process that requires the coordinated interaction
      of osteocytes, osteoblasts, and osteoclasts, collaborating in basic multicellular
      units (BMUs). Communication between these cells can be by extracellular soluble
      molecules as well as directly propagating intercellular signalling molecules. Key
      to the understanding of bone remodelling is osteocyte mechanosensing and chemical
      signalling to the surrounding cells, since osteocytes are believed to be the
      mechanosensors of bone, responding to mechanical stresses. Nitric oxide (NO) is
      an important parameter to study osteocyte activation following mechanical
      loading. It is a small short-lived molecule, which makes its real-time,
      quantitative monitoring difficult. However, recently we demonstrated that DAR-4M
      AM chromophore can be used for real-time quantitative monitoring of intracellular
      NO production in individual cells following mechanical loading. Here we studied
      if a single mechanically stimulated osteocyte communicates with, and thus
      activates its surrounding cells via extracellular soluble factors. We monitored
      quantitatively intracellular NO production in the stimulated osteocyte and in its
      surrounding osteocytes, which were not interconnected. Mechanical stimulation by
      microneedle of a single-MLO-Y4 osteocyte-like cell upregulated the average
      intracellular NO production by 94% in the stimulated cell, and by 31-150% in the
      surrounding osteocytes. In conclusion, a single osteocyte can disseminate a
      mechanical stimulus to its surrounding osteocytes via extracellular soluble
      signalling factors. This reinforces the putative mechanosensory role of
      osteocytes, and demonstrates a possible mechanism by which a single mechanically
      stimulated osteocyte can communicate with other cells in a BMU, which might help
      to better understand the intricacies of intercellular interactions in BMUs and
      thus bone remodelling.

PMID- 17512531
TI  - Grafting of montmorillonite with different functional silanes via two different
      reaction systems.
AB  - Silane grafted montmorillonites were synthesized by using 3
      aminopropyltriethoxysilane and trimethylchlorosilane via two different grafting
      reaction systems: (a) ethanol-water mixture and (b) vapor of silane. The
      resulting products were investigated using Fourier transform infrared (FTIR), X
      ray diffraction (XRD), thermogravimetric analysis (TGA). XRD patterns demonstrate
      that silane was intercalated into the montmorillonite gallery, as indicated by
      the increase of the basal spacing. The product prepared by vapor deposition has a
      larger basal spacing than that obtained from solution, due to the different
      extent of silane hydrolysis in various grafting systems. TGA curves indicate that
      the methyl groups penetrate into the siloxane clay are the primary reason for the
      decrease of the dehydroxylation temperature of the grafted products. 3
      Aminopropyltriethoxysilane in the grafted montmorillonite adopts a bilayer
      arrangement while trimethylchlorosilane adopts a monolayer arrangement within the
      clay gallery.

PMID- 17512532
TI  - Shedding new light on an old problem: The estimation of shadow sizes in children
      and adults.
AB  - Two experiments using the 'projection of shadows' paradigm investigated
      multidimensional reasoning, implicit and explicit knowledge, and the nonlinearity
      concept in 5-, 9-, and 13-year-olds and adults. Participants estimated the
      resulting shadow lengths of differently sized objects, placed at varying
      distances from a light source. Experiment 1 (N=80) revealed that, on the group
      level, 5-year-olds took both object size and light-object distance into account
      when estimating shadow size. Moreover, half of the children in this age group
      even considered the subordinate distance dimension. In addition, we found a large
      discrepancy between implicit and explicit knowledge about shadows in 5-year-olds
      that decreased with age. Finally, only a minority of older participants and very
      few younger children recognized the nonlinear relationship between light-object
      distance and shadow size, suggesting domain dependence of the nonlinearity
      concept. Experiment 2 (N=20) predominately replicated the findings for 5-year
      olds using slightly different stimuli.

PMID- 17512533
TI  - Formulation of vaccines containing CpG oligonucleotides and alum.
AB  - CpG oligodeoxynucleotides are potent immunostimulants. For parenterally delivered
      alum-based vaccines, the immunostimulatory effect of CpG depends on the
      association of the CpG and antigen to the alum. We describe effects of buffer
      components on the binding of CPG 7909 to aluminum hydroxide (Alhydrogel), assays
      for measuring binding of CPG 7909 to alum and CPG 7909 induced dissociation of
      antigen from the alum. Free CPG 7909 is a potent inducer of IP-10 in mice.
      However the lack of IP-10 production from formulations containing bound CPG 7909
      suggested that CPG 7909 does not rapidly dissociate from the alum after
      injection. It also suggests that IP-10 assays are not a good basis for potency
      assays for alum-based vaccines containing CPG 7909.

PMID- 17512534
TI  - Fluorochrome-linked immunoassay for functional analysis of the mannose binding
      lectin complement pathway to the level of C3 cleavage.
AB  - The humoral response to invading pathogens is mediated by a repertoire of innate
      immune molecules and receptors able to recognize pathogen-associated molecular
      patterns. Mannose binding lectin (MBL) and ficolins are initiation molecules of
      the lectin complement pathway (LCP) that bridge innate and adaptive immunity.
      Activation of the MBL-dependent lectin pathway, to the level of C3 cleavage,
      requires functional MASP-2, C2, C4 and C3, all of which have been identified with
      genetic polymorphisms that can affect protein concentration and function. Current
      assays for MBL and MASP-2 lack the ability to assess activation of all components
      to the level of C3 cleavage in a single assay platform. We developed a novel, low
      volume, fluorochrome linked immunoassay (FLISA) that quantitatively assesses the
      functional status of MBL, MASP-2 and C3 convertase in a single well. The assay
      can be used with plasma or serum. Multiple freeze/thaw cycles of serum do not
      significantly alter the assay, making it ideal for high throughput of large
      sample databases with minimal volume use. The FLISA can be used potentially to
      identify specific human disease correlations between these components and
      clinical outcomes in already established databases.

PMID- 17512535
TI  - Proteinase, amylase, and proteinase-inhibitor activities in the gut of six
      cockroach species.
AB  - Representative species, two from each of the cockroach families Blattidae,
      Blattellidae, and Blaberidae, have similar morphology of the digestive tract but
      differ in the physiology of digestion. The pH of crop and along the midgut varies
      in different species from 5.9 to 9.0 and the redox parameter from 10.1 to 12.9.
      Activities of proteinases and amylases in comparable gut regions differ among the
      species up to 100 times. Proteolytic activity is high in the midgut and moderate
      in the crop of Blattidae; in the other species, it is very low in the crop and
      increases to a moderate level in the posterior half of midgut (PM). The level of
      amylolytic activity is similar in the examined gut compartments of Blattidae and
      Blattellidae but low in the PM of Blaberidae. Blaberidae are also characterized
      by a high potential of the salivary glands, crop, and midgut to inhibit
      subtilisin, trypsin, and chymotrypsin. Inhibition of these proteinases by the
      extracts of salivary glands and gut is several orders of magnitude lower and
      often undetectable in the representatives of Blattidae and Blattellidae.

PMID- 17512536
TI  - Expression and function of ATP-dependent potassium channels in late post
      infarction remodeling.
AB  - Myocardial remodeling late after infarction is associated with increased
      incidence of fatal arrhythmias. Heterogeneous prolongation of the action
      potential in the surviving myocardium is one of the predominant causes.
      Sarcolemmal ATP-dependent potassium (K(ATP)) channels are important metabolic
      sensors regulating electrical activity of cardiomyocytes and are capable of
      considerably shortening the action potential. We determined whether ATP-dependent
      potassium channels generate or, on the contrary prevent the heterogeneity in
      action potential prolongation. Cardiomyocytes were obtained from the infarct
      border zone, the septum and the right ventricle of rat hearts 20 weeks after
      coronary occlusion when rats developed signs of heart failure. Expression of the
      conductance subunit Kir6.1, but not Kir6.2, and of all SUR regulatory subunits
      was increased up to 3-fold in cardiomyocytes from the infarct border zone.
      Concomitantly, there was a prominent response of the K(ATP) current to diazoxide
      that was not detectable in control cardiomyocytes. The action potential was
      prolonged in cardiomyocytes from the infarct border zone (74 ms) relative to sham
      (41 ms). However, activation of the K(ATP) channels by diazoxide reduced action
      potential duration to 42 ms. In myocytes of the septum and right ventricle,
      expression of channel subunits, duration of action potential, and sensitivity to
      diazoxide were only slightly increased relative to shams. In conclusion, the
      myocardium remodeled after infarction displays alterations of K(ATP) expression
      and function with spatial heterogeneity matching that of the action potential
      prolongation. Drugs selectively activating diazoxide-sensitive sarcolemmal K(ATP)
      channels should be considered in the prevention of arrhythmias in post-infarction
      heart failure.

PMID- 17512537
TI  - Two-stage folding of HP-35 from ab initio simulations.
AB  - Accurate ab initio simulation of protein folding is a critical step toward
      elucidation of protein-folding mechanisms. Here, we demonstrate highly accurate
      folding of the 35 residue villin headpiece subdomain (HP35) by all-atom molecular
      dynamics simulations using AMBER FF03 and the generalized-Born solvation model.
      In a set of 20 micros long simulations, the protein folded to the native state in
      multiple trajectories, with the lowest C(alpha) RMSD being 0.39 A for residues 2
      34 (excluding residues 1 and 35). The native state had the highest population
      among all sampled conformations, and the center of most populated cluster had a
      C(alpha) RMSD of 1.63 A. Folding of this protein can be described as a two-stage
      process that followed a well-defined pathway. In the first stage, formation of
      helices II and III as a folding intermediate constituted the rate-limiting step
      and was initiated at a folding nucleus around residues Phe17 and Pro21. The
      folding intermediate further acted as a template that facilitated the folding and
      docking of helix I in the second stage. Detailed descriptions of the folding
      kinetics and the roles of key residues are presented.

PMID- 17512539
TI  - Stable intermediate states and high energy barriers in the unfolding of GFP.
AB  - We present a study of the denaturation of a truncated, cycle3 variant of green
      fluorescent protein (GFP). Chemical denaturation is used to unfold the protein,
      with changes in structure being monitored by the green fluorescence, tyrosine
      fluorescence and far-UV circular dichroism. The results show that the
      denaturation behaviour of GFP is complex compared to many small proteins:
      equilibrium is established only very slowly, over the time course of weeks,
      suggesting that there are high folding/unfolding energy barriers. Unfolding
      kinetics confirm that the rates of unfolding at low concentrations of denaturant
      are very low, consistent with the slow establishment of the equilibrium. In
      addition, we find that GFP significantly populates an intermediate state under
      equilibrium conditions, which is compact and stable with respect to the unfolded
      state (m(IU)=4.6 kcal mol(-1) M(-1) and Delta G(IU)=12.5 kcal mol(-1)). The
      global and local stability of GFP was probed further by measuring the
      hydrogen/deuterium (H/D) NMR exchange rates of more than 157 assigned amide
      protons. Analysis at two different values of pH showed that amide protons within
      the beta-barrel structure exchange at the EX2 limit, consequently, free energies
      of exchange could be calculated and compared to those obtained from the
      denaturation-curve studies providing further support for the three-state model
      and the existence of a stable intermediate state. Analysis reveals that amide
      protons in beta-strands 7, 8, 9 and 10 have, on average, higher exchange rates
      than others in the beta-barrel, suggesting that there is greater flexibility in
      this region of the protein. Forty or so amide protons were found which do not
      undergo significant exchange even after several months and these are clustered
      into a core region encompassing most of the beta-strands, at least at one end of
      the barrel structure. It is likely that these residues play an important role in
      stabilizing the structure of the intermediate state. The intermediate state
      observed in the chemical denaturation studies described here, is similar to that
      observed at pH 4 in other studies.

PMID- 17512538
TI  - Change in nutritional status modulates the abundance of critical pre-initiation
      intermediate complexes during translation initiation in vivo.
AB  - In eukaryotic translation initiation, eIF2GTP-Met-tRNA(i)(Met) ternary complex
      (TC) interacts with eIF3-eIF1-eIF5 complex to form the multifactor complex (MFC),
      while eIF2GDP associates with eIF2B for guanine nucleotide exchange. Gcn2p
      phosphorylates eIF2 to inhibit eIF2B. Here we evaluate the abundance of eIFs and
      their pre-initiation intermediate complexes in gcn2 deletion mutant grown under
      different conditions. We show that ribosomes are three times as abundant as eIF1,
      eIF2 and eIF5, while eIF3 is half as abundant as the latter three and hence, the
      limiting component in MFC formation. By quantitative immunoprecipitation, we
      estimate that approximately 15% of the cellular eIF2 is found in TC during rapid
      growth in a complex rich medium. Most of the TC is found in MFC, and important,
      approximately 40% of the total eIF2 is associated with eIF5 but lacks
      tRNA(i)(Met). When the gcn2Delta mutant grows less rapidly in a defined complete
      medium, TC abundance increases threefold without altering the abundance of each
      individual factor. Interestingly, the TC increase is suppressed by eIF5
      overexpression and Gcn2p expression. Thus, eIF2B-catalyzed TC formation appears
      to be fine-tuned by eIF2 phosphorylation and the novel eIF2/eIF5 complex lacking
      tRNA(i)(Met).

PMID- 17512540
TI  - Kinetic isotope effects reveal the presence of significant secondary structure in
      the transition state for the folding of the N-terminal domain of L9.
AB  - Our present understanding of the nature of the transition state for protein
      folding depends predominantly on studies where individual side-chain
      contributions are mapped out by mutational analysis (phi value analysis). This
      approach, although extremely powerful, does not in general provide direct
      information about the formation of backbone hydrogen bonds. Here, we report the
      results of amide H/D isotope effect studies that probe the development of
      hydrogen bonded interactions in the transition state for the folding of a small
      alpha-beta protein, the N-terminal domain of L9. Replacement of amide protons by
      deuterons in a solvent of constant isotopic composition destabilized the domain,
      decreasing both its T(m) and Delta G(0) of unfolding. The folding rate also
      decreased. The parameter Phi(H/D), defined as the ratio of the effect of isotopic
      substitution upon the activation free energy to the equilibrium free energy was
      determined to be 0.6 in a D(2)O background and 0.75 in a H(2)O background,
      indicating that significant intraprotein hydrogen bond interactions are developed
      in the transition state for the folding of NTL9. The value is in remarkably good
      agreement with more traditional measures of the position of the transition state,
      which report on the relative burial of surface area. The results provide a
      picture of a compact folding transition state containing significant secondary
      structure. Indirect analysis argues that the bulk of the kinetic isotope effect
      arises from the beta-sheet-rich region of the protein, and suggests that the
      development of intraprotein hydrogen bonds in this region plays a critical role
      in the folding of NTL9.

PMID- 17512541
TI  - The structurally disordered KRAB repression domain is incorporated into a
      protease resistant core upon binding to KAP-1-RBCC domain.
AB  - The KRAB domain is a 75 amino acid transcriptional repression module that is
      encoded by more than 400 zinc finger protein genes, making it the most abundant
      repression domain in the human proteome. KRAB-mediated gene silencing requires a
      direct high affinity interaction with the RBCC domain of KAP-1 co-repressor. The
      structures of the free KRAB domain or the KRAB-RBCC complex are unknown. To
      address this, we have performed a systematic biophysical analysis of all KRAB
      isoforms using purified recombinant proteins. All KRAB domains are predominantly
      monomeric either alone or in a complex with KAP-1-RBCC protein, while a KRAB-SCAN
      isoform exists as a stable dimer. The KRAB:KAP-1-RBCC interaction requires only
      the A box in the context of the KRAB(Ab) or KRAB(AC) but both A and B boxes in
      the context of KRAB(AB). All isoforms bind the KAP-1-RBCC in a stable, zinc
      dependent fashion with a stoichiometry of KRAB1:3 RBCC with a zinc content of
      four atoms per RBCC monomer. Limited proteolysis, mass spectrometry and N
      terminal sequence analyses suggest that a core complex comprises the entire RBCC
      domain of KAP-1 and the AB box of the KRAB domain rendering it resistant to
      proteolysis. NMR spectroscopy showed that unbound KRAB domain does not exist as a
      well-folded globular protein in solution but may fold into an ordered structure
      upon binding to the KAP-1-RBCC protein. This is the first example of a
      structurally disordered repressor domain that is the most widely conserved
      silencing domain in tetrapods.

PMID- 17512542
TI  - Dissecting the non-specific and specific components of the initial folding
      reaction of barstar by multi-site FRET measurements.
AB  - Initial polypeptide chain collapse plays a major role in the development of
      subsequent structure during protein folding, but it has been difficult to
      elucidate the coupling between its cooperativity and specificity. To better
      understand this important aspect of protein folding, nine different
      intramolecular distances in the protein have been measured by fluorescence
      resonance energy transfer (FRET) in the product(s) of the initial, sub
      millisecond collapse reaction during the folding of barstar, under different
      folding conditions. All nine distances contract in these initial folding
      products, when the denaturant concentration is reduced. Two of these distances
      were also measured in peptides corresponding to sequence segments 38-55 and 51-69
      of the protein. Surprisingly, both distances do not contract in the peptides
      which remain fully unfolded when the denaturant concentration is reduced. This
      suggests that the contraction of at least some segments of the polypeptide chain
      may be facilitated only by contraction of other segments. In the case of the
      initial product of folding of the protein, the dependence on denaturant
      concentration of the relative change in each distance suggests that there are two
      components to the initial folding reaction. One is a nonspecific component, which
      appears to be driven by the change in denaturant concentration that is used to
      initiate refolding. This component corresponds to the collapse of completely
      unfolded protein (U) to unfolded protein in refolding conditions (U(C)). The
      extent of nonspecific collapse can be predicted by the response of completely
      unfolded protein to a change in denaturant concentration. All distances undergo
      such solvent-induced contraction, but each distance contracts to a different
      extent. There is also a specific component to initial sub-millisecond folding, in
      which some distances (but not all) contract more than that predicted by solvent
      induced contraction. The observation that only some of the distances undergo
      contraction over and above solvent-induced contraction, suggest that this
      specific component is associated with the formation of a specific intermediate
      (I(E)). FRET efficiency and distance change differently for the different donor
      acceptor pairs, with a change in denaturant concentration, indicating that the
      formation or dissolution of structure in U(C) and I(E) does not happen in a
      synchronized manner across different regions of the protein molecule. Also, all
      nine FRET efficiencies and intramolecular distances in the product(s) of sub-ms
      folding, change continuously with a change in denaturant concentration. Hence, it
      appears that the transitions from U to U(C) and to I(E) are gradual
      transformations, and not all-or-none structural transitions. Nevertheless, the
      product of these gradual transitions, I(E), possesses specific structure.

PMID- 17512543
TI  - Solution structure of the Ubp-M BUZ domain, a highly specific protein module that
      recognizes the C-terminal tail of free ubiquitin.
AB  - The BUZ/Znf-UBP domain is a distinct ubiquitin-binding module found in the
      cytoplasmic deacetylase HDAC6, the E3 ubiquitin ligase BRAP2/IMP, and a subfamily
      of deubiquitinating enzymes. Here, we report the solution structure of the BUZ
      domain of Ubp-M, a ubiquitin-specific protease, and its interaction with
      ubiquitin. Unlike the BUZ domain from isopeptidase T (isoT) that contains a
      single zinc finger, the Ubp-M BUZ domain features three zinc-binding sites
      consisting of 12 residues. These zinc ligands form a pair of cross-braced ring
      fingers encapsulated within a third zinc finger in the primary structure. In
      contrast to isoT, which can form an N-terminal loop swapped dimer in the crystal
      state, the formation of additional zinc fingers in the Ubp-M BUZ domain restricts
      its N-terminal loop to intra-domain interactions. The ubiquitin-binding site of
      the Ubp-M BUZ domain is mapped to the highly conserved, concave surface formed by
      the alpha 3 helix and the central beta-sheet. We further show that this site
      binds to the C-terminal tail of free ubiquitin, and corresponding peptides
      display essentially the same binding affinities as full-length ubiquitin does for
      the Ubp-M BUZ domain. However, modification of the G76(Ub) carboxylate group
      either by a peptide or isopeptide bond abolishes BUZ-domain interaction. The
      unique ubiquitin-recognition mode of the BUZ domain family suggests that they may
      function as "sensors" of free ubiquitin in cells to achieve regulatory roles in
      many aspects of ubiquitin-dependent processes.

PMID- 17512544
TI  - An intra-aortic shunt prevents paralysis during aortic surgery in sheep.
AB  - INTRODUCTION: Sheep are recommended by the United States Food and Drug
      Administration as a model for testing cardiovascular tissue, but are particularly
      prone to spinal cord ischemia and subsequent paralysis during aortic cross
      clamping. METHODS: A shunt consisting of a 9 cm long phosphorylcholine coated 1/4
      in. (i.d.) polyvinylchloride tube was inserted through the aortotomy into the
      aorta to provide blood flow across the operative site. Blood pressure and flow in
      the distal aorta were measured continuously with an indwelling femoral artery
      catheter and an ultrasonic aortic flow probe. The hemodynamic effects were
      measured in seven 45 to 55 kg Suffolk sheep. This shunt was then used to implant
      decellularized pulmonary artery patches into 25 animals. RESULTS: Occlusion of
      the aorta reduced the distal mean aortic pressure from 86.4 +/- 4.6 mmHg to 1.79
      +/- 0.4 mmHg (P < 0.001) and opening the intra-aortic shunt restored the distal
      mean aortic pressure to 67.9 +/- 7.3 mmHg (P = 0.053). Blood flow in the distal
      aorta was 2.35 +/- 0.37 L/min at baseline and was reduced to -0.01 +/- 0.01 L/min
      (P < 0.001) with the aorta cross-clamped and returned to 2.49 +/- 0.36 L/min (P =
      0.945) when the shunt was opened. Use of this shunt prevented hind leg paralysis
      in all 24 animals surviving the procedure. CONCLUSIONS: A simple intra-aortic
      shunt was effective in restoring blood pressure and flow in the aorta distal to
      the operative site and prevented hind leg paralysis associated with aortic
      clamping.

PMID- 17512545
TI  - NMR assessment of Me(2)SO in decellularized cryopreserved aortic valve conduits.
AB  - INTRODUCTION: Decellularized cryopreserved allograft vascular tissue may provide
      a nonimmunogenic scaffold that is suitable for repopulation by cells from a
      variety of sources, conferring the potential for growth and repair. Although
      dimethyl sulfoxide (Me(2)SO) is generally regarded as a safe cryoprotectant, even
      low levels may alter function of repopulating cells. We investigated the residual
      concentration of Me(2)SO in the aqueous compartment of cryopreserved ovine aortic
      valve conduits following decellularization. MATERIALS AND METHODS: Aortic valve
      conduits from Suffolk sheep were cryopreserved in 1.1 M (7.5% vol/vol) Me(2)SO
      according to the protocol of our local tissue bank. Three aortic valve conduits
      were decellularized in a series of hypotonic and hypertonic Tris buffers. Tissue
      samples were taken at regular time intervals throughout the decellularization
      process and equilibrated in double distilled, deionized H(2)O for 28 days.
      Quantitative proton nuclear magnetic resonance spectroscopy was used to determine
      the residual Me(2)SO concentration in the equilibration solutions from which
      Me(2)SO tissue concentrations were calculated. RESULTS: After thawing, the mean
      Me(2)SO concentration in the valve conduit was 0.302 +/- 0.081 M. The
      decellularization process resulted in a stepwise reduction in the Me(2)SO
      concentration to less than 8.56 x 10(-5) +/- 9 x 10(-5) M (P = 0.02). The
      diffusion coefficient was 2.5 x 10(-6) cm(2)/s. CONCLUSIONS: Our study
      demonstrates that Me(2)SO is effectively washed out of the aortic valve conduit
      during decellularization, resulting in a final concentration that is several
      orders of magnitude less than Me(2)SO concentrations reported to alter cell
      function.

PMID- 17512546
TI  - Effective ablation of pancreatic cancer cells in SCID mice using systemic
      adenoviral RIP-TK/GCV gene therapy.
AB  - BACKGROUND: Studies have demonstrated that adenovirus subtype 5 mediated rat
      insulin promoter directed thymidine kinase (A-5-RIP-TK)/ganciclovir (GCV) gene
      therapy resulted in significant enhanced cytotoxicity to both PANC-1 and MIA
      PaCa2 pancreatic cancer cells in vitro. However, little is known about the effect
      in vivo. In this study we examine the in vivo safety and efficacy of intravenous
      A-5-RIP-TK/GCV gene therapy. MATERIALS AND METHODS: 1 x 10(6) Mia PaCa2 cells
      were injected intraperitoneally (i.p.) into SCID mice to create a mouse model of
      human pancreatic cancer. A-5-RIP-TK gene construct was administered intravenously
      (i.v.), followed by i.p. GCV administration. Intravenous injection of A-5-RIP
      lacZ reporter gene constructs was used for evaluation of Ad-RIP-gene expression
      in tumors and other tissues. Optimal adenoviral and GCV doses and treatment
      duration were determined. Tumor volume, serum insulin, and glucose levels were
      measured. Immunohistochemical staining of pancreata and tumors were performed to
      assess morphology and hormone expression and apoptotic rates were determined.
      RESULTS: All A-5-RIP-TK/GCV-treated mice had reduced tumor volume compared with
      controls, but maximal tumor volume reduction was observed with 10(8) vp followed
      by GCV treatment for 4 wk. A-5-RIP-TK/GCV gene therapy contributed to significant
      survival advantage in MIA PaCa2 bearing mice, and the greatest survival benefit
      was observed with 10(8) vp and was not affected by length of treatment of GCV. A
      5-RIP-TK/GCV therapy increased PDX-1 expression and tumor cells apoptosis, and
      altered islet morphology. However, A-5-RIP-TK/GCV gene therapy caused diabetes
      associated with islet cell apoptosis, increased delta-cells and reduced
      pancreatic polypeptide (PP)-cell numbers. CONCLUSIONS: Systemically administered
      A-5-RIP-TK/GCV is an effective treatment of pancreatic cancer. A-5-RIP-TK/GCV
      cytotoxicity to malignant cells varies with adenoviral dose and length of GCV
      treatment. However, A-5-RIP-TK/GCV is associated with islet cell toxicity and
      diabetogenesis. The type of diabetes observed is distinct from Types 1 and 2 and
      is associated with islet cell apoptosis and reduced delta- and PP-cells.

PMID- 17512547
TI  - Role of VIP and substance P in NANC innervation in the longitudinal smooth muscle
      of the rat jejunum - influence of extrinsic denervation.
AB  - BACKGROUND: This study was designed to determine changes in nonadrenergic,
      noncholinergic (NANC) neurotransmission mediated by Vasoactive Intestinal
      Polypeptide (VIP) and Substance P after small bowel transplantation (SBT).
      MATERIALS AND METHODS: Six groups of rats (n > or = 6 per group) were studied:
      naive controls (NC); 1 wk after anesthesia/sham celiotomy (SC-1); 1 or 8 wk after
      jejunal and ileal transection/reanastomosis (TA-1, TA-8), or syngeneic,
      orthotopic SBT (SBT-1, SBT-8). Jejunal longitudinal muscle strips were studied
      under NANC-conditions for spontaneous contractile activity, response to exogenous
      VIP and Substance P, and electrical field stimulation (EFS). RESULTS: Spontaneous
      activity did not differ between the six groups. VIP inhibited contractile
      activity in all groups 1 wk postoperatively (P < 0.05), which was prevented by
      the NO synthase inhibitor L-N(G)-nitro arginine (L-NNA). In contrast, VIP had no
      effect in the other groups. Precontraction with Substance P exposed an inhibitory
      effect of VIP in all groups (P < 0.05 each). Substance P increased contractile
      activity in all groups, but to a lesser extent in SBT-8 compared with NC, TA-8,
      and SBT-1 (P < 0.05). The inhibitory effect of EFS at 6 Hz was prevented by L-NNA
      in NC and TA-8; addition of the VIP antagonist ([D-p-Cl-Phe(6), Leu(17)]-VIP)
      increased contractile activity in NC, but not in TA-8 and SBT-8. The Substance P
      antagonist ([D-Pro(2), D-Trp(7,9)]-Substance P) decreased contractile activity
      during EFS at 50 Hz in NC and SBT-8. CONCLUSIONS: SBT decreased response to
      exogenous Substance P, although release of endogenous Substance P (EFS) is
      preserved. Changes in VIP signaling are acute and reversible and not caused by
      effects of SBT.

PMID- 17512548
TI  - Outcomes for soft-tissue sarcoma in 8249 cases from a large state cancer
      registry.
AB  - BACKGROUND AND OBJECTIVES: To date, outcome reports for soft-tissue sarcoma (STS)
      have largely been limited to single or paired institutional series. To more
      accurately elucidate population-based outcomes and prognostic factors associated
      with STS, a large cancer registry was examined. METHODS: STS arising in the
      Florida Cancer Data System were examined (1981-2004). RESULTS: A total of 8249
      patients were identified, the calculated annual incidence of sarcoma being
      approximately 38 cases per million in 2003. The tumor histologies among these
      patients were leiomyosarcoma and gastrointestinal stromal tumor (LMS/GIST)
      (43.5%), malignant fibrous histiocytoma (MFH) (31.5%), liposarcoma (19.0%), and
      fibrosarcoma (6.0%). Tumors were situated in the extremities (30.7%), truncal or
      visceral locations (50.4%), retroperitoneum (11.7%), and head or neck (7.2%).
      Thirty-three percent of lesions were over 10 cm in greatest dimension, while
      50.2% were classified as high grade. Median overall survival was 25 months.
      Superior survival was observed for liposarcomas and fibrosarcomas as compared to
      MFH and LMS/GIST (P < 0.001). Retroperitoneal and truncal sarcomas had a more
      ominous prognosis than did other sites (P < 0.001). Multivariate analysis of
      pretreatment variables demonstrated that increasing age, male gender, non
      Caucasian race, advanced stage, and a truncal or retroperitoneal location were
      each independently associated with lower survival. Histological subtype was also
      an independent predictor of outcome. Surgical resection and radiation therapy
      were the only treatment variables shown to improve survival. CONCLUSIONS:
      Histological subtype, tumor site, and stage are independent prognostic factors in
      STS. Surgical resection and radiotherapy are unique among treatment modalities in
      association with a significant survival benefit.

PMID- 17512549
TI  - A model of heterotopic aortic valve replacement for studying thromboembolism
      prophylaxis in mechanical valve prostheses.
AB  - OBJECTIVES: New anticoagulants, such as direct thrombin inhibitors, have been
      evaluated in prevention of thromboembolism associated with atrial fibrillation
      and may also be useful for thromboprophylaxis of mechanical heart valves.
      Preclinical studies are necessary prior to human trials, but the best animal
      model is unknown. We, therefore, compared thrombogenicity in two porcine models
      of mechanical valve replacement, a standard preparation for mitral valve
      implantation and a simplified heterotopic model of aortic valve replacement.
      METHODS: Thirteen swine underwent either mitral valve replacement (n = 6) or
      heterotopic aortic valve replacement (n = 7) with bileaflet mechanical valve
      substitutes. The heterotopic aortic valve replacement consisted of an extra
      anatomical, modified valved conduit bypassing the ligated native descending
      thoracic aorta. At 30 d, the animals were sacrificed and the amount of valve
      thrombus was measured. RESULTS: Infectious vegetations were present on two valve
      prostheses in animals with orthotopic mitral valves and were excluded. Mean
      thrombus weight for the remaining valves was 216 +/- 270 mg [95% CI -35, 466] for
      the animals with heterotopic aortic valve replacement and 74 +/- 67 mg [95% CI 
      33, 180] for animals with orthotopic mitral valve replacement (P = 0.5).
      CONCLUSION: A porcine, heterotopic aortic mechanical valve replacement model
      appears to incite more thrombus formation than does an orthotopic mitral valve
      replacement model. This appears to be a more stringent model for initial testing
      of novel anticoagulation strategies for mechanical heart valve
      thromboprophylaxis.

PMID- 17512550
TI  - The effect of hepatic vascular inflow occlusion on liver tissue pH, carbon
      dioxide, and oxygen partial pressures: defining the optimal clamp/release regime
      for intermittent portal clamping.
AB  - BACKGROUND: The optimal duration of hepatic vascular inflow occlusion (Pringle
      maneuver) and reperfusion during liver resection are not defined. The aim of this
      study was to describe the changes that occur in liver tissue pH, partial pressure
      of carbon dioxide (P(L)CO(2)), and partial pressure of oxygen (P(L)O(2)) and by
      using the P(L)CO(2) as a predictor of hepatocellular damage define the optimal
      clamp/release regime for intermittent portal clamping during liver resection.
      METHODS: Continuous pH, P(L)CO(2), and P(L)O(2) measurements were obtained using
      a Paratrend multi-parameter sensor (Diametrics Medical Inc., Roseville, MN) in 13
      patients undergoing elective partial liver resection. Patients were randomly
      allocated to undergo a 10-min clamp/5-min release regime (group 1) or a 20-min
      clamp/10-min release regime (group 2). RESULTS: In group 1 (n = 6) P(L)CO(2)
      increased and pH decreased significantly after 10 min of clamping and returned to
      baseline within 5 min of reperfusion. In group 2 (n = 7) the P(L)CO(2) increased
      and pH decreased significantly after 10 min of clamping, with a further
      significant change after 20 min. Following 10 min of reperfusion, pH and
      P(L)CO(2) had not returned to baseline. P(L)O(2) did not change significantly
      with either intermittent portal clamping regime. CONCLUSIONS: A reperfusion of 5
      min is sufficient to restore the P(L)CO(2) and liver tissue pH to normal after 10
      min of clamping, but more than 10 min of reperfusion is required after 20 min of
      clamping. To minimize hepatic ischemia during liver resection, a 10-min clamp/5
      min release regime should be used.

PMID- 17512551
TI  - Progress in shivering control.
AB  - Hypothermia is a potent neuroprotectant and induced hypothermia holds great
      promise as a therapy for acute neuronal injury. Thermoregulatory responses, most
      notably shivering, present major obstacles to therapeutic temperature management.
      A review of thermoregulatory physiology and strategies aimed at controlling
      physiologic responses to hypothermia is presented.

PMID- 17512552
TI  - Food-web complexity emerging from ecological dynamics on adaptive networks.
AB  - Food webs are complex networks describing trophic interactions in ecological
      communities. Since Robert May's seminal work on random structured food webs, the
      complexity-stability debate is a central issue in ecology: does network
      complexity increase or decrease food-web persistence? A multi-species predator
      prey model incorporating adaptive predation shows that the action of ecological
      dynamics on the topology of a food web (whose initial configuration is generated
      either by the cascade model or by the niche model) render, when a significant
      fraction of adaptive predators is present, similar hyperbolic complexity
      persistence relationships as those observed in empirical food webs. It is also
      shown that the apparent positive relation between complexity and persistence in
      food webs generated under the cascade model, which has been pointed out in
      previous papers, disappears when the final connection is used instead of the
      initial one to explain species persistence.

PMID- 17512553
TI  - Application of a changing field of growth rates to a description of root apex
      formation.
AB  - Based on the growth tensor method an unsteady field of growth rates for
      developing root apex is presented. Maps of growth rates distribution as well as
      simulations in which the field was applied to initially uniform grid of points
      are presented. In the simulations, the grid undergoes deformation that resembles
      new root formation in its axial plane. Four variants of field operation on the
      grid are shown.

PMID- 17512554
TI  - Nebivolol induces eNOS activation and NO-liberation in murine corpus cavernosum.
AB  - Erectile function is critically dependent upon the activation of the endothelial
      nitric oxide synthase (eNOS) in the smooth muscle cells of penile corpus
      cavernosum tissue. Nebivolol is a beta(1)-selective beta-adrenoceptor blocker
      (beta-ARB) with additional vasodilating properties, which have been attributed to
      eNOS-activation. Our study investigated whether nebivolol is able to increase
      eNOS activity in erectile tissue. Murine penile tissue was incubated in an organ
      bath under control conditions and in the presence of nebivolol or metoprolol.
      Immunofluorescence staining was performed using specific antibodies against eNOS
      activation or eNOS-serine 1177 phosphorylation. Corpus cavernosum smooth muscle
      tissue was identified using a smooth muscle actin antibody. In addition, slices
      of murine erectile tissue were incubated with diaminofluorescein (DAF), a
      specific fluorescence marker for NO-liberation. Under control conditions and
      after application of metoprolol, we observed a small eNOS-activation and serine
      1177-phosphorylation in murine corpus cavernosum tissue. A significant increase
      in eNOS-activation and serine 1177-phosphorylation of eNOS was observed only in
      the presence of nebivolol (10 muM). These alterations of the eNOS protein induced
      after application of nebivolol were associated with a time-dependent increase in
      DAF fluorescence in murine erectile tissue. We conclude that beta-adrenoceptor
      blockers differentially influence erectile tissue. Since cardiovascular diseases
      are often associated with the development of erectile dysfunction, the nebivolol
      induced eNOS-activation in corpus cavernosum may be beneficial when treating
      patients suffering from cardiovascular disease.

PMID- 17512555
TI  - Changes in extracellular activin A:follistatin ratio during differentiation of a
      mesenchymal progenitor cell line, ROB-C26 into osteoblasts and adipocytes.
AB  - We investigated the effects of BMP-2 and dexamethasone (Dex) on follistatin (FS)
      and activin A expressions in a mesenchymal progenitor cell line, ROB-C26 (C26).
      C26 cells stimulated to differentiate into osteoblastic cells by blocking
      myogenic differentiation after BMP-2 treatment and into adipocytes with Dex
      treatment. Alkaline phosphatase (ALP) mRNA expression and its activity in the
      confluent C26 cells were dose- and time-dependently stimulated by BMP-2, but
      inhibited by Dex. The stimulatory effect on FS and activin A mRNA expressions by
      BMP-2 and Dex were dose-dependent. Cycloheximide pre-treatment indicated that FS
      and activin A expressions appear to be the direct target of BMP-2 and Dex
      signaling. BMP-2 time-dependently increased FS and activin A levels. Dex also
      increased FS level, but induced a time-dependent biphasic effect on activin A
      level, a decrease (2-6 h) followed by an increase (12-72 h). The data of the
      ratio of activin A concentration in the culture media to that of FS (activin A:FS
      ratio) measured by ELISA showed that BMP-2-induced osteoblastic differentiation
      involved an activin-dominant microenvironment, whereas Dex-induced adipocyte
      differentiation involved a FS-dominant microenvironment. Excess FS suppressed the
      stimulatory ALP activity of BMP-2, whereas activin A prevented not only Dex
      induced inhibitory ALP activity, but also adipogenesis via suppression of the
      adipocyte transcriptional factor cascade. These results indicate that BMP-2
      induced activin-dominant microenvironment may be critical for osteoblastic
      differentiation by restricting the antagonistic effects of FS on BMP activity,
      while Dex-induced FS-dominant microenvironment may be critical for adipocyte
      differentiation by restricting the inhibitory action of activin A on adipocyte
      differentiation.

PMID- 17512556
TI  - Endocrine-disrupting phenols in selected rivers and bays in the Philippines.

PMID- 17512557
TI  - Influence of the Pearl River estuary and vertical mixing in Victoria Harbor on
      water quality in relation to eutrophication impacts in Hong Kong waters.
AB  - This study presents water quality parameters such as nutrients, phytoplankton
      biomass and dissolved oxygen based on 11 years of water quality data in Victoria
      Harbor and examined how the Pearl River estuary discharge in summer and year
      round sewage discharge influenced these parameters. Nutrients in Victoria Harbor
      were strongly influenced by both the Pearl River and sewage effluent, as
      indicated by the high NO(3) inputs from the Pearl River in summer and higher
      NH(4) and PO(4) in Victoria Harbor than both its sides. N:P ratios were low in
      the dry season, but increased to >16:1 in the wet season, suggesting that P is
      potentially the most limiting nutrient in this area during the critical period in
      the summer. Although there were generally high nutrients, the phytoplankton
      biomass was not as high as one would expect in Victoria Harbor. In fact, there
      were high concentrations of chl near the bottom well below the photic zone.
      Salinity near the bottom was lower in Victoria Harbor than at the two entrances
      to Victoria Harbor, suggesting strong vertical mixing within Victoria Harbor.
      Therefore, strong vertical mixing and horizontal advection appear to play an
      important role in significantly reducing eutrophication impacts in Victoria
      Harbor. Consequently, dissolved oxygen near the bottom was low in summer, but
      only occasionally dipped to 2 mgL(-1) despite the high organic loading from
      sewage effluent.

PMID- 17512558
TI  - On some optimization problems in molecular biology.
AB  - In the last two decades, the study of gene structure and function and molecular
      genetics have become some of the most prominent sub-fields of molecular biology.
      Computational molecular biology has emerged as one of the most exciting
      interdisciplinary fields, riding on the success of the ongoing Human Genome
      Project, which culminated in the 2001 announcement of the complete sequencing of
      the human genome. The field has currently benefited from concepts and theoretical
      results obtained by different scientific research communities, including
      genetics, biochemistry, and computer science. It is only in the past few years
      that it has been shown that a large number of molecular biology problems can be
      formulated as combinatorial optimization problems, including sequence alignment
      problems, genome rearrangement problems, string selection and comparison
      problems, and protein structure prediction and recognition. This paper provides a
      detailed description of some among the most interesting molecular biology
      problems that can be formulated as combinatorial optimization problems and
      proposes a new heuristic to find improved solutions for a particular class of
      them, known as the far from most string problem.

PMID- 17512559
TI  - Mutant spectra of irradiated CHO AL cells determined with multiple markers
      analyzed by flow cytometry.
AB  - We have previously developed a sensitive and rapid mammalian cell mutation assay
      which is based on a Chinese hamster ovary cell line that stably incorporates
      human chromosome 11 (CHO A(L)) and uses flow cytometry to measure mutations in
      CD59. We now show that multiparameter flow cytometry may be used to
      simultaneously analyze irradiated CHO A(L) cells for mutations in five CD genes
      along chromosome 11 (CD59, CD44, CD90, CD98, CD151) and also a GPI-anchor gene.
      Using this approach, 19 different mutant clones derived from individual sorted
      mutant cells were analyzed to determine the mutant spectrum induced by ionizing
      radiation. All clones analyzed were negative for CD59 expression and PCR
      confirmed that at least CD59 exon 4 was also absent. As expected, ionizing
      radiation frequently caused large deletions along chromosome 11. This technology
      can readily be used to rapidly analyze the mutant yield as well as the spectrum
      of mutations caused by a variety of genotoxic agents and provide greater insight
      into the mechanisms of mutagenesis.

PMID- 17512560
TI  - Sustained increase of alpha7 nicotinic receptors and choline-induced improvement
      of learning deficit in STOP knock-out mice.
AB  - Mice deficient in the microtubule stabilizing protein STOP (stable tubule only
      polypeptide) show synaptic plasticity anomalies in hippocampus, dopamine hyper
      reactivity in the limbic system and severe behavioral deficits. Some of these
      disturbances are alleviated by long-term antipsychotic treatment. Therefore, this
      mouse line represents a pertinent model for some aspects of schizophrenia
      symptomatology. Numerous data support dysfunction of nicotinic neurotransmission
      in schizophrenia and epidemiological studies show increased tobacco use in
      schizophrenic patients, in whom nicotine has been reported to improve cognitive
      deficits and impairment in sensory gating. In this study, we examined potential
      alterations in cholinergic (ACh) and nicotinic components and functions in STOP
      mutant mice. STOP KO mice displayed no variation of the density of ACh esterase
      and beta2* nicotinic receptors (nAChRs), large reductions in the density of
      vesicular ACh transporter and alpha6* nAChRs and marked increases in the density
      of alpha7 nAChRs, in some brain areas. STOP KO mice were hypersensitive to the
      stimulating locomotor effect of nicotine and, interestingly, their impaired
      performance in learning the cued version of the water maze were improved by
      administration of the preferential alpha7 nAChR agonist choline. Altogether, our
      data show that the deletion of the ubiquitous STOP protein elicited restricted
      alterations in ACh components. They also suggest that nicotinic neurotransmission
      can be deficient in STOP KO mice and that mutant mice can represent a meaningful
      model to study some nicotinic dysfunctions and therapeutic treatments.

PMID- 17512561
TI  - Bilateral damage to the mammillo-thalamic tract impairs recollection but not
      familiarity in the recognition process: a single case investigation.
AB  - Focal damage confined to the hippocampus may result in recognition deficits
      characterized by a dissociation between impaired recollection and preserved
      familiarity. Here, we report a single case of an amnesic patient with bilateral
      damage to the anterior part of the thalamus, who presented with a
      neuropsychological profile suggesting such a dissociation. We hypothesized that
      this focal damage involved the so-called Delay and Brion's circuit, which has
      been theorized to subserve episodic memory processes, but at a different
      anatomical level than in patients with hippocampal lesions. Using two independent
      experimental paradigms (remember/know and confidence receiver operating
      characteristics [ROC]) and recruiting a sex- and age-matched group of healthy
      controls, we demonstrated that this patient's recognition deficits were due to a
      selective impairment of recollection with a normal familiarity process. The
      patient underwent an ad hoc brain MRI study, and a quantitative analysis of his
      MR images was performed. Tissue damage extended bilaterally to the mammillo
      thalamic tract, with complete preservation of the medio-dorsal thalamic nuclei.
      Our findings support the idea that the same functional specialization
      hypothesized for the different sub-regions of the mesial temporal lobe might also
      extend to the thalamus. This case will be discussed in light of its implications
      in support of recent theories, which regard recollection and familiarity as
      independent processes associated with different neural circuits.

PMID- 17512563
TI  - Bufadienolides from the southern African Drimia depressa (Hyacinthaceae:
      Urgineoideae).
AB  - Two bufadienolides, 3beta,16beta-dihydroxy-5beta-bufa-20,22-dienolide and 16beta
      hydroxy-5beta-bufa-20,22-dienolide-3beta-O-beta-d-galactoside, have been isolated
      from bulbs of the poisonous South African geophyte Drimia depressa
      (Hyacinthaceae).

PMID- 17512564
TI  - Proteomic analysis of Chelidonium majus milky sap using two-dimensional gel
      electrophoresis and tandem mass spectrometry.
AB  - Milky sap, a milky-like orange fluid, isolated from the Greater Celandine
      (Chelidonium majus L.), family Papaveraceae, serves as a rich source of various
      biologically active substances such as alkaloids, several flavonoids, phenolic
      acids and proteins. The objective of this study was to separate Ch. majus milky
      sap extract proteins using two-dimensional gel electrophoresis (2-DE) to
      demonstrate for the first time the protein composition in the sap and to identify
      them using liquid chromatography-tandem mass spectrometry analysis (LC-ESI
      MS/MS). It was possible to identify 21 proteins, which comprise disease/defence
      related, signalling, Krebs cycle, nucleic acid binding and other proteins. The
      majority of the identified proteins can be linked to direct and indirect stress
      and defence reactions, e.g. against different pathogens. The specific protein
      composition of the milky sap suggests an important role of these proteins for the
      whole plant physiology and development.

PMID- 17512562
TI  - Dynamic body weight and body composition changes in response to subordination
      stress.
AB  - Social stress is prevalent in many facets of modern society. Epidemiological data
      suggest that stress is linked to the development of overweight, obesity and
      metabolic disease. Although there are strong associations between the incidence
      of obesity with stress and elevated levels of hormones such as cortisol, there
      are limited animal models to allow investigation of the etiology of increased
      adiposity resulting from exposure to stress. Perhaps more importantly, an animal
      model that mirrors the consequences of stress in humans will provide a vehicle to
      develop rational clinical therapy to treat or prevent adverse outcomes from
      exposure to chronic social stress. In the visible burrow system (VBS) model of
      chronic social stress mixed gender colonies are housed for 2 week periods during
      which male rats of the colony quickly develop a dominance hierarchy. We found
      that social stress has significant effects on body weight and body composition
      such that subordinate rats progressively develop characteristics of obesity that
      occurs, in part, through neuroendocrine alterations and changes in food intake
      amount. Although subordinate rats are hyperphagic following social stress they do
      not increase their intake of sucrose solution as control and dominants do
      suggesting that they are anhedonic. Consumption of a high fat diet does not
      appear to affect development of a social hierarchy and appears to enhance the
      effect that chronic stress has on body composition. The visible burrow system
      (VBS) model of social stress may be a potential laboratory model for studying
      stress-associated metabolic disease, including the metabolic syndrome.

PMID- 17512565
TI  - Shot noise perturbations and mean first passage times between stable states.
AB  - Predicting crossings between stable states is a central issue in population
      biology. Crossings from low-density to high-density equilibria are often
      associated with pest outbreaks, while the opposite crossings are often associated
      with population collapse of harvested species. Here I use a simple, bistable
      model to demonstrate a technique for estimating mean first passage times (MFPT)
      of thresholds, including boundaries between stable equilibria. The approach is
      based on stochastic "shot-noise" perturbations to the population and the MFPTs
      compare favorably with mean crossing times from Monte Carlo numerical solutions
      of the stochastically perturbed model. This agreement suggests that MFPT
      approximations can be used to quantify expected effects of species manipulations,
      whether the goal is pest control or sustainable harvest.

PMID- 17512566
TI  - Tributyltin induces apoptotic signaling in hepatocytes through pathways involving
      the endoplasmic reticulum and mitochondria.
AB  - Tri-n-butyltin is a widespread environmental toxicant, which accumulates in the
      liver. This study investigates whether tri-n-butyltin induces pro-apoptotic
      signaling in rat liver hepatocytes through pathways involving the endoplasmic
      reticulum and mitochondria. Tri-n-butyltin activated the endoplasmic reticulum
      pathway of apoptosis, which was demonstrated by the activation of the protease
      calpain, its translocation to the plasma membrane, followed by cleavage of the
      calpain substrates, cytoskeletal protein vinculin, and caspase-12. Caspase-12 is
      localized to the cytoplasmic side of the endoplasmic reticulum and is involved in
      apoptosis mediated by the endoplasmic reticulum. Tri-n-butyltin also caused
      translocation of the pro-apoptotic proteins Bax and Bad from the cytosol to
      mitochondria, as well as changes in mitochondrial membrane permeability, events
      which can activate the mitochondrial death pathway. Tri-n-butyltin induced
      downstream apoptotic events in rat hepatocytes at the nuclear level, detected by
      chromatin condensation and by confocal microscopy using acridine orange. We
      investigated whether the tri-n-butyltin-induced pro-apoptotic events in
      hepatocytes could be linked to perturbation of intracellular calcium homeostasis,
      using confocal microscopy. Tri-n-butyltin caused changes in intracellular calcium
      distribution, which were similar to those induced by thapsigargin. Calcium was
      released from a subcellular compartment, which is likely to be the endoplasmic
      reticulum, into the cytosol. Cytosolic acidification, which is known to trigger
      apoptosis, also occurred and involved the Cl(-)/HCO(3)(-) exchanger. Pro
      apoptotic events in hepatocytes were inhibited by the calcium chelator, Bapta-AM,
      and by a calpain inhibitor, which suggests that changes in intracellular calcium
      homeostasis are involved in tri-n-butyltin-induced apoptotic signaling in rat
      hepatocytes.

PMID- 17512568
TI  - Purification and characterization of antitoxic proteins from the serum of
      Agkistrodon halys Pallas.
AB  - In this study, the authors report the purification and characterization of
      antitoxic proteins from the serum of Agkistrodon halys Pallas. Two antitoxic
      proteins have been successfully isolated by the methods of (NH4)(2)SO(4)
      fractional precipitation, chromatography and preparative discontinuous
      polyacrylamide gel electrophoresis (PAGE). We have measured their molecular
      weights by Sephadex G-150 chromatography and 0.1% SDS-Tris-HCl discontinue PAGE
      respectively. Antitoxin I was about 138,000+/-40 Da and antitoxin II was about
      76,000+/-40 Da, they are all single-chain peptides. We have measured their
      capacity to neutralize the toxicity of agkistrodotoxin (ATX), and their capacity
      to inhibit the PLA(2) activity of ATX. The results showed that antitoxin I could
      increase LD(50) of ATX from 0.25+/-0.05 to 0.445+/-0.13 mg/kg, decrease its
      PLA(2) activity from 2.36 to 1.72 microm/mg min, and antitoxin II could increase
      LD(50) of ATX from 0.25+/-0.05 to 0.56+/-0.12 mg/kg, decrease Phospholipase A(2)
      (PLA(2)) activity from 2.36 to 1.2 microm/mg min. When the natural antitoxins
      were mixed with different amounts of ATX and inoculated intraperitonially into
      eight mice, it was found that 0.5 mg antitoxin I could neutralize the toxicity of
      0.4 mg ATX and 0.5 mg antitoxin II could neutralize the toxicity of 0.5 mg ATX
      completely. These antitoxic proteins could neutralize the toxicity of ATX
      completely and inhibit ATX's PLA(2) activity partially.

PMID- 17512567
TI  - Lead effects on development and function of bone marrow-derived dendritic cells
      promote Th2 immune responses.
AB  - Although lead (Pb) has significant effects on the development and function of
      macrophages, B cells, and T cells and has been suggested to promote allergic
      asthma in mice and humans, Pb modulation of bone marrow (BM)-derived dendritic
      cells (DCs) and the resultant DC effects on Th1 and Th2 development have not been
      examined. Accordingly, we cultured BM cells with murine granulocyte macrophage
      colony stimulating factor (mGM-CSF)+/-PbCl(2). At day 10, culture supernatant
      (SN) and non-adherent cells were harvested for analysis. Additionally, day 10 non
      adherent BM-DCs were harvested and recultured with mGM-CSF+LPS+/-Pb for 2 days.
      The day 10 Pb exposure significantly inhibited BM-DC generation, based on CD11c
      expression. Although fewer DCs were generated with Pb, the existing Pb-exposed
      DCs had significantly greater MHC-II expression than did the non-Pb-exposed DCs.
      However, these differences diminished upon LPS stimulation. After LPS
      stimulation, CD80, CD86, CD40, CD54, and MHC-II were all up-regulated on both Pb
      DCs and DCs, but Pb-DCs expressed significantly less CD80 than did DCs. The
      CD86:CD80 ratio suggests a Pb-DC potential for Th2 cell development. After LPS
      stimulation, IL-6, IL-10, IL-12 (p70), and TNF-alpha levels significantly
      increased with both Pb-DCs and DCs, but Pb-DCs produced significantly less
      cytokines than did DCs, except for IL-10, which further supports Pb-DC
      preferential skewing toward type-2 immunity. In vitro studies confirm that Pb-DCs
      have the ability to polarize antigen-specific T cells to Th2 cells. Pb-DCs also
      enhanced allogeneic and autologous T cell proliferation in vitro, and in vivo
      studies suggested that Pb-DCs inhibited Th1 effects on humoral and cell-mediated
      immunity. The Pb effect was mainly on DCs, rather than on T cells, and Pb's
      modification of DC function appears to be the main cause of Pb's promotion of
      type-2-related immunity, which may relate to Pb's enhanced activation of the
      Erk/MAP kinase pathway.

PMID- 17512569
TI  - Cellular homeoproteins, SATB1 and CDP, bind to the unique region between the
      human cytomegalovirus UL127 and major immediate-early genes.
AB  - An AT-rich region of the human cytomegalovirus (CMV) genome between the UL127
      open reading frame and the major immediate-early (MIE) enhancer is referred to as
      the unique region (UR). It has been shown that the UR represses activation of
      transcription from the UL127 promoter and functions as a boundary between the
      divergent UL127 and MIE genes during human CMV infection [Angulo, A., Kerry, D.,
      Huang, H., Borst, E.M., Razinsky, A., Wu, J., Hobom, U., Messerle, M., Ghazal,
      P., 2000. Identification of a boundary domain adjacent to the potent human
      cytomegalovirus enhancer that represses transcription of the divergent UL127
      promoter. J. Virol. 74 (6), 2826-2839; Lundquist, C.A., Meier, J.L., Stinski,
      M.F., 1999. A strong negative transcriptional regulatory region between the human
      cytomegalovirus UL127 gene and the major immediate-early enhancer. J. Virol. 73
      (11), 9039-9052]. A putative forkhead box-like (FOX-like) site, AAATCAATATT, was
      identified in the UR and found to play a key role in repression of the UL127
      promoter in recombinant virus-infected cells [Lashmit, P.E., Lundquist, C.A.,
      Meier, J.L., Stinski, M.F., 2004. Cellular repressor inhibits human
      cytomegalovirus transcription from the UL127 promoter. J. Virol. 78 (10), 5113
      5123]. However, the cellular factors which associate with the UR and FOX-like
      region remain to be determined. We reported previously that pancreatic-duodenal
      homeobox factor-1 (PDX1) bound to a 45-bp element located within the UR [Chao,
      S.H., Harada, J.N., Hyndman, F., Gao, X., Nelson, C.G., Chanda, S.K., Caldwell,
      J.S., 2004. PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of
      Human Cytomegalovirus Immediate Early Promoter. J. Biol. Chem. 279 (16), 16111
      16120]. Here we demonstrate that two additional cellular homeoproteins, special
      AT-rich sequence binding protein 1 (SATB1) and CCAAT displacement protein (CDP),
      bind to the human CMV UR in vitro and in vivo. Furthermore, CDP is identified as
      a FOX-like binding protein and a repressor of the UL127 promoter, while SATB1 has
      no effect on UL127 expression. Since CDP is known as a transcription repressor
      and a nuclear matrix-associated region binding protein, CDP may have a role in
      the regulation of human CMV transcription.

PMID- 17512570
TI  - Anisotropy for spatial summation of elongated patches of grating: a tale of two
      tails.
AB  - Studies of spatial summation often use sinusoidal gratings with blurred edges.
      When the envelope is elongated (i) along the grating stripes and (ii) at right
      angles to the grating stripes, we refer to the stimuli as skunk-tails and tiger
      tails respectively. Previous work [Polat & Tyler, 1999; Vision Research, 39, 887
      895.] has found that sensitivity to skunk-tails is greater than for tiger-tails,
      but there have been several failures to replicate this result within a subset of
      the conditions. To address this we measured detection thresholds for skunk-tails,
      tiger-tails and squares of grating with sides matched to the lengths of the
      tails. For foveal viewing, we found a contrast sensitivity advantage in the order
      of 2dB for skunk-tails over tiger-tails, but only for horizontal gratings. For
      vertical gratings, sensitivity was very similar for both tail-types. When the
      stimuli were presented parafoveally (upper right visual field), a small advantage
      was found for skunk-tails over tiger-tails at both orientations, and spatial
      summation slopes were close to that of the ideal observer. We did not replicate
      the findings of Polat & Tyler, but our results are consistent with (i) those of
      Foley et al. [Foley, J. M., Varadharajan, S., Koh, C. C., & Farias, C. Q. (2007)
      Vision Research, 47, 85-107.] who used only vertical gratings and (ii) those from
      modelfest, where only horizontal gratings were used. The small effect of tail
      type here suggests an anisotropy in the underlying physiology.

PMID- 17512571
TI  - Decolorisation of real textile waste using electrochemical techniques: effect of
      the chloride concentration.
AB  - The present paper presents the study of the decolorisation of real textile
      effluent by constant current electrolysis in a flow-cell using a
      Ti/Ru(0.3)Ti(0.7)O(2) DSA type electrode. The effect of increasing the chloride
      ion concentration on the efficiency of colour removal is discussed. Attempts to
      perform galvanostatic oxidation (40 and 60 mA cm(-2)) on the as-received effluent
      demonstrate that colour removal and total organic carbon (TOC) removal are
      limited. If the conductivity of the effluent is increased by adding 0.033 mol L(
      1) Na(2)SO(4), little increase in the extent of colour/TOC removal is observed.
      However, when Na(2)SO(4) is substituted, stepwise, with NaCl (while maintaining
      the ionic strength constant) appreciable colour/TOC removal is observed. The
      study of the effect of increasing the current density demonstrates that total
      colour removal is possible at high currents. The efficiencies of colour and TOC
      removal are discussed in terms of the Energy per order (E(EO)/kWh m(-3)order(-1))
      and Energy consumption (E(C)/kWh kg(-1)TOC), respectively. Finally, the extent of
      colour removal is compared to consent levels presented in the literature.

PMID- 17512572
TI  - The impact of psychological functioning upon systemic sclerosis patients' quality
      of life.
AB  - OBJECTIVE: To access health-related quality of life (HRQOL) in systemic sclerosis
      (SSc) patients using the World Health Organization Quality of Life Instrument,
      Short-Form (WHOQOL-BREF), and to identify the association between clinical,
      psychopathological, and personality parameters and SSc patients' HRQOL. METHODS:
      Fifty-six patients with SSc were compared with 72 patients with rheumatoid
      arthritis (RA), 43 with systemic lupus erythematosus (SLE), 34 with Sjogren
      syndrome (SS), and 74 healthy controls. A wide range of clinical information was
      collected and the following self-report instruments were used: the WHOQOL-BREF,
      the General Health Questionnaire, the Symptom Distress Check List, the Hostility
      and Direction of Hostility Questionnaire, the Defense Style Questionnaire, and
      the Sense of Coherence scale. RESULTS: HRQOL perceived by SSc patients was
      significantly impaired compared with healthy controls. Initial examination of
      HRQOL across groups of rheumatology patients revealed similar HRQOL, but when
      age, pain, psychopathology, and coping strategies were taken into account, SSc
      patients had impaired physical health QOL in comparison with RA, SLE, and SS
      patients. Arthritis-related pain was closely associated with SSc patients' HRQOL.
      Elevated psychological distress symptoms as well as certain personality traits,
      such as maladaptive defenses and lower sense of coherence, were also associated
      with diminished HRQOL. CONCLUSIONS: Impaired psychological functioning is
      associated with diminished HRQOL in SSc, and consequently, treatment of
      depressive symptoms should be considered a priority. Moreover, assessment of
      HRQOL should only be used in conjunction with specific psychological distress
      measurements, to detect the influence of psychopathology on HRQOL.

PMID- 17512573
TI  - PON1, a new biomarker of cardiovascular disease, is low in patients with systemic
      vasculitis.
AB  - OBJECTIVES: Because systemic vasculitis (SV) predisposes to atherosclerosis, and
      high-density lipoprotein (HDL) prevents atherosclerosis by "reverse cholesterol
      transport" and by inhibiting low-density lipoprotein (LDL) oxidation thanks to
      apolipoprotein A-I (Apo-AI) and paraoxonase 1 (PON1), we assessed whether LDL
      oxidation was increased in SV and associated with less PON1 activity. METHODS:
      The sera of 33 patients with active SV (ASV), 32 in full remission of SV (RSV)
      and 20 healthy subjects (HS) were analyzed for C-reactive protein (CRP), high
      sensitivity-CRP, lipids, lipoproteins, apolipoproteins, PON1 activity, LDL-immune
      complexes (LDL-IC), and auto-antibodies to oxidized-LDL (ox-LDL), and
      anticardiolipin antibodies. RESULTS: CRP was higher in ASV than RSV and HS, and
      negatively correlated with HDL-cholesterol and Apo-AI. Autoantibodies to ox-LDL
      and highly oxidized malondialdehyde-LDL were higher in RSV than ASV and HS
      (P<0.05). LDL-IC titers were higher in ASV than RSV and HS (P<0.05). PON1
      activity was lower in ASV and RSV than HS (P=0.02). A trend toward a negative
      correlation between basal PON1 activity and anti-MDA-LDL antibodies (P=0.06) was
      observed. CONCLUSION: Inflammatory markers in SV were associated with a modified
      lipoprotein profile, which could lower PON1 activity and contribute to increased
      ox-LDL titers and accelerated atherosclerosis development.

PMID- 17512575
TI  - Pegylated liposomal doxorubicin treatment in recurrent gynecologic cancer
      patients with renal dysfunction.
AB  - OBJECTIVES: A paucity of data exists regarding the efficacy and toxicity of
      pegylated liposomal doxorubicin (PLD) in cancer patients with chronic kidney
      disease (CKD). We sought to investigate the toxicity and efficacy of PLD in
      gynecologic cancer patients with CKD. METHODS: The clinical records of all
      patients with recurrent gynecological cancer and CKD at the University of Texas
      M.D. Anderson Cancer Center from 08/1999 to 08/2006 were reviewed retrospectively
      to identify patients who received PLD. RESULTS: Twenty-eight patients were
      identified, which included 14 with epithelial ovarian cancer, 4 with peritoneal
      cancer, and 10 with other gynecologic cancers. CKD was defined as a creatinine
      clearance (CrCl) of <90 ml/min/1.73 m(2) and classified as mild (5 patients),
      moderate (16 patients), or severe (7 patients) (CrCl 60-89, 30-59, and <30
      ml/min/1.73 m(2), respectively). The initial doses of PLD were classified into
      regular initial dose (40 mg/m(2)/4 weeks) and lower initial dose (30-35 mg/m(2)/4
      weeks). The median cycle was 4.5 (range 1-17). The incidence of grade 3-4 palmar
      plantar erythrodysesthesia, stomatitis, and hematologic toxicity was 11.1%
      (2/18), 5.6% (1/18), and 16.7% (3/18) among 18 patients with an initial dose of
      40 mg/m(2)/4 weeks, which included 5, 10, and 3 patients with mild, moderate, and
      severe CKD, respectively. Dose reduction due to toxicities occurred in 33.3%
      (6/18) patients. In 18 patients with ovarian and peritoneal cancer (all platinum
      resistant), the rates of complete response, partial response, stable disease, and
      progression were 0%, 11.1%, 44.4%, and 44.4%, respectively. CONCLUSIONS: Patients
      with CKD who received PLD therapy at an initial dose of 40 mg/m(2)/4 weeks may
      require greater subsequent dose reduction mainly secondary to mucocutaneous and
      hematologic toxicities. Treatment response in this population with ovarian and
      peritoneal cancer was similar to that of patients with normal renal function.

PMID- 17512574
TI  - Efficacy of antithrombin in the prevention of microvascular thrombosis during
      endotoxemia: an intravital microscopic study.
AB  - INTRODUCTION: The KyberSept trial in septic patients showed that antithrombin
      (AT) reduced 90-day mortality significantly in a subgroup of patients not
      receiving concomitant heparin for thrombosis prophylaxis. Microvascular
      thrombosis is a key pathophysiologic mechanism during sepsis,
      ischemia/reperfusion and disseminated intravascular coagulation (DIC). Therefore,
      this study investigated the antithrombotic property of AT as potential
      monotherapy in an experimental endotoxemia model in order to omit concomitant
      heparin. MATERIALS AND METHODS: Using a light/dye injury model in the ear and the
      cremaster muscle preparation of mice, we quantitatively assessed microvascular
      thrombus formation in a total of 30 endotoxemic mice by means of intravital
      fluorescence microscopy. Before thrombus induction animals received a single i.v.
      bolus of AT (100 or 250 IU/kg), heparin (100 IU/kg) or saline (NaCl). RESULTS: In
      NaCl-treated endotoxemic animals, light/dye exposure led to complete thrombotic
      occlusion in arterioles and venules within <450 s in the ear model. Heparin
      delayed thrombotic vessel occlusion by more than 50%. AT significantly prolonged
      times until thrombotic vessel occlusion in a dose-dependent manner and more
      effectively than heparin (p<0.05 vs. NaCl and heparin). This anti-coagulative
      effect of AT was especially pronounced in arterioles. Upon light/dye exposure to
      cremaster muscle preparations in endotoxemic mice AT also caused a 4-fold delay
      in microvascular thrombus growth with 827+/-77 s until complete thrombotic
      occlusion. CONCLUSIONS: We could characterize for the first time AT-mediated
      antithrombotic activity during endotoxemia in two models of phototoxicity-induced
      microvascular thrombosis. Our results clearly demonstrate an additional AT
      mechanism of action that may be responsible for beneficial effects observed
      during endotoxemia and DIC. This AT profile may allow future high-dose AT
      application without giving heparin for thrombosis prophylaxis, an intriguing
      strategy that is to be tested under clinical conditions.

PMID- 17512576
TI  - Arsenic trioxide (As2O3) reduces the invasive and metastatic properties of
      cervical cancer cells in vitro and in vivo.
AB  - OBJECTIVES: Arsenic trioxide (As(2)O(3)) was found to induce apoptosis in certain
      types of cancer cells including acute promyelocytic leukemia, and recently in
      solid tumors. We have previously demonstrated that As(2)O(3) has a therapeutic
      effect on cervical cancer by apoptosis promotion in vitro and in vivo. Here we
      further our study on the role of arsenic trioxide in regulating invasive activity
      of cervical cancer cells in vitro and in vivo. METHODS: The effects of As(2)O(3)
      on human cervical cancer cell lines (HeLa, SiHa, Caski) adhesion, migration and
      invasion were observed by means of cell adhesion test, cell migration test and
      cell invasion test. The effects of As(2)O(3) on p-IkappaB, MMP-2, E-cadherin,
      caveolin-1 and beta-catenin protein expressions of tumor cells were determined by
      Western blot. In addition, the effects of As(2)O(3) on NF-kappaB activity of
      tumor cells were analyzed by immunoblot in whole lysates, cytosol and nucleus,
      respectively. In animal experiments, cervical cancer cells TC-1 were injected
      into tail veins of C57BL/6 mice and then the mice were treated by intraperitoneal
      injection of different doses As(2)O(3). Lung weights and the foci on the surface
      of lungs were measured. RESULTS: As(2)O(3) inhibited attachment of tumor cells to
      Fibronectin and Matrigel, reduced cell motility and inhibited tumor invasion
      potential. As(2)O(3) treatment also resulted in a positive regulation of caveolin
      1, upregulation of E-cadherin and decreased activity of beta-catenin, NF-kappaB
      and NF-kappaB-regulated gene MMP-2. In animal experiments, lung weights in PBS
      group (0.31+/-0.07 g) were significantly elevated compared with those in
      As(2)O(3)-treated groups (0.21+/-0.03 g and 0.17+/-0.03 g) also As(2)O(3) reduced
      number of metastatic lesions of lungs (15.4+/-3.5 vs. 8.3+/-2.0 and 6.3+/-2.3) in
      a dose-dependent manner. CONCLUSIONS: This study is the first to report the
      effectiveness of As(2)O(3) as an inhibitor of cervical cancer invasion both in
      vitro and in vivo, suggesting a potential clinical application of As(2)O(3) in
      cervical cancer therapies combining apoptosis induction and metastasis
      inhibition.

PMID- 17512578
TI  - Disinfection procedures for controlling microorganisms in the semen and embryos
      of humans and farm animals.
AB  - Semen and embryos generated by assisted reproductive techniques (ARTs) may be
      contaminated with numerous microorganisms. Contamination may arise from systemic
      or local reproductive tract infections in donors or the inadvertent introduction
      of microorganisms during ARTs, and may lead to disease transmission. This review
      describes sanitary procedures which have been investigated to ascertain whether
      they are effective in rendering semen and embryos free of pathogenic
      microorganisms, including internationally adopted washing procedures, which can
      be supplemented by antibiotics and enzymatic treatments. Other methods include
      treatment with antibodies or ozone, photoinactivation, acidification, and the use
      of novel antiviral compounds. In conclusion, despite the wide range of
      antimicrobial procedures available, none can be recommended as a universal
      disinfection method for rendering semen and embryos free from all potentially
      pathogenic microorganisms. However, some procedures are unsuitable, as they can
      compromise the viability of semen or embryos. In humans, washing by the gradient
      centrifugation method appears to be effective for reducing the microbial
      population in semen and is harmless to the spermatozoa. A useful procedure for
      embryos involving multiple washes in sterile medium has much to commend it for
      the prevention of disease transmission; furthermore, it is recommended by the
      International Embryo Transfer Society (IETS).

PMID- 17512577
TI  - The IL-1 type 1 receptor is required for the development of LPS-induced airways
      disease.
AB  - BACKGROUND: The contribution of IL-1beta signaling through the IL-1 type 1
      receptor (IL-1R1) to the development of persistent LPS-induced airway disease has
      not been investigated. OBJECTIVE: To determine the importance of signaling
      through the IL-1 type 1 receptor in the development of LPS-induced airway
      disease. METHODS: We exposed IL-1R1-deficient (C57BL/6(IL-1RI-/-)) mice to an
      aerosol of LPS or filtered air for 1 day, 1 week, or 4 weeks. RESULTS: After 4
      weeks of LPS inhalation, C57BL/6(IL-1RI-/-) mice failed to develop significant
      submucosal thickening, whereas C57BL/6 mice had significantly thickened submucosa
      in small, medium, and large airways compared with those of unexposed control
      mice. Cell proliferation in the airways of both the 1-week and 4-week LPS-exposed
      C57BL/6(IL-1RI-/-) mice was significantly reduced compared with LPS-exposed
      C57BL/6 mice. mRNA for type III alpha-3 procollagen was significantly elevated
      over baseline in C57BL/6 yet remained unchanged compared with baseline in
      C57BL/6(IL-1RI-/-) mice after 1 week or 4 weeks of LPS inhalation. mRNA for
      tissue inhibitor of metalloprotease 1 in C57BL/6 mice in the 1-week and 4-week
      groups was significantly elevated over both control mice and C57BL/6(IL-1RI-/-)
      mice. CONCLUSION: These data support the hypothesis that signaling through the IL
      1 receptor modulates extracellular matrix homeostasis in response to inhaled LPS.
      CLINICAL IMPLICATIONS: Attenuating IL-1R1-mediated signaling might be an
      effective therapy against the development of airway remodeling in chronic
      inflammatory diseases.

PMID- 17512579
TI  - Mucus and the mare: how little we know.
AB  - Uterine infections are a major cause of infertility, but the role of mucus in
      equine uterine defense is not well understood. Mucociliary currents play an
      important role in protecting mucous membranes, including the upper and lower
      respiratory tracts of mammals, and are required for feeding and oxygenation of
      many aquatic invertebrates. Although phagocytosis has long been considered the
      first line of uterine defense in the mare, there are concerns about its efficacy
      in the uterine lumen. Additional local defenses, such as mucociliary currents,
      have therefore been proposed. The uterine epithelium exhibits alternating mucus
      secreting and ciliated cells supporting a mucopolysaccharide blanket, features
      shared with mucociliary membranes throughout the animal kingdom. Gross uterine
      anatomy, such as continuity of uterine and cervical folds, may indicate
      adaptations to mucociliary clearance. In addition, ciliated cells obtained in
      uterine lavages often display motility. Disruptions of mucociliary clearance play
      major roles in pathogenesis of mucosal infections in humans, including pneumonia,
      chronic sinusitis, and otitis media. Establishing drainage is a major goal of
      therapy in treatment of chronic sinusitis, hastening return of mucociliary
      function. Similar disruptions may occur in equine uterine infections, associated
      with accumulations of uterine fluid, loss of endometrial folds, and cervical
      trauma. Possible clinical implications of mucociliary clearance in the mare are
      discussed, however the role of mucociliary clearance in the mare remains
      speculative.

PMID- 17512581
TI  - Role of aldosterone availability in preeclampsia.
AB  - Preeclampsia is a hypertensive disorder unique to pregnancy and remains the
      leading cause of maternal and fetal morbidity and mortality. Despite active
      research, the etiology of this disease remains still an enigma. There is
      increasing evidence that a combination of several factors is responsible for the
      development of preeclampsia. In this review, we discuss the role of aldosterone
      in the regulation of body fluid in pregnancy and preeclampsia. Aldosterone is
      produced by the enzyme aldosterone synthase and competes with cortisol and
      progesterone for the mineralocorticoid receptor, thus affecting sodium
      reabsorption and maternal volume expansion. Aldosterone seems to play a pivotal
      role in controlling blood pressure during pregnancy and to contribute to the well
      being of the mother-to-be. Novel findings in understanding the underlying causes
      of preeclampsia provide a rationale for future novel prophylactic and therapeutic
      interventions in the treatment of this pregnancy-associated disease.

PMID- 17512582
TI  - Occurrence and seasonal variations of algal toxins in water, phytoplankton and
      shellfish from North Stradbroke Island, Queensland, Australia.
AB  - A number of marine microalgae are known to produce toxins that can accumulate in
      shellfish and when eaten, lead to toxic and potentially fatal reactions in
      humans. This paper reports on the occurrence and seasonal variations of algal
      toxins in the waters, phytoplankton and shellfish of Southeast Queensland,
      Australia. These algal toxins include okadaic acid (OA), domoic acid (DA),
      gymnodimine (GD), pectenotoxin-2 (PTX-2) and pectenotoxin-2-seco acid (PTX-2-SA),
      which were detected in the sampled shellfish and phytoplankton, via HPLC-MS/MS.
      Dissolved OA, PTX-2 and GD were also detected in the samples collected from the
      water column. This was the first occasion that DA and GD have been reported in
      shellfish, phytoplankton and the water column in Queensland waters. Phytoplankton
      tows contained both the toxic Dinophysis and Pseudo-nitzschia algae species, and
      are suspected of being the most likely producers of the OA, PTX-2s and DA found
      in shellfish of this area. The number of cells, however, did not correlate with
      the amount of toxins present in either shellfish or phytoplankton. This indicates
      that toxin production by algae varies with time and the species present and that
      number of cells alone cannot be used as an indicator for the presence of toxins.
      The presence of OA and PTX-2s were more frequently seen in the summer, while DA
      and GD were detected throughout the year and without any obvious seasonal
      patterns.

PMID- 17512583
TI  - Alkaline phosphatase-induced mineral deposition to anchor collagen fibrils to a
      solid surface.
AB  - Reconstruction of tendon and ligament tissues requires proper attachment of the
      tissue-engineered construct to surrounding tissues. A problem of reconstructing
      collagen-rich tissues is that an in vitro engineered collagenous network
      containing fibroblasts will contract and detach from a solid surface. In vivo
      anchorage of soft connective tissues to mineralized tissues like bones and teeth
      is accomplished by embedding collagen fibrils into mineralized layers.
      Mineralization is partially the result of local activity of the enzyme alkaline
      phosphatase (ALP). In this study, we tested whether ALP-induced mineral
      deposition at the interface between a collagen gel and a polystyrene or
      polyetheretherketone (PEEK) surface could prevent gel detachment from the
      surface. Coating of culture wells with intestinal ALP prevented detachment of
      gels harbored with human periodontal ligament (PDL) fibroblasts in the presence
      of its substrate beta-glycerophosphate. Mineral deposition was observed
      predominantly at the interface of collagen gel and well surface. The contractile
      properties of fibroblasts were not influenced by either ALP, beta
      glycerophosphate or both. The presence of ALP on a solid surface and providing
      its substrate to allow mineral deposition can prevent detachment of collagen
      matrices. Our findings provide a tool to induce attachment of fibrillar collagen
      to a solid surface; an approach that seems useful for reconstruction of load
      bearing tissues and attachment of ligaments to implants.

PMID- 17512584
TI  - Transient inter-cellular polymeric linker.
AB  - Three-dimensional (3D) tissue-engineered constructs with bio-mimicry cell-cell
      and cell-matrix interactions are useful in regenerative medicine. In cell-dense
      and matrix-poor tissues of the internal organs, cells support one another via
      cell-cell interactions, supplemented by small amount of the extra-cellular
      matrices (ECM) secreted by the cells. Here we connect HepG2 cells directly but
      transiently with inter-cellular polymeric linker to facilitate cell-cell
      interaction and aggregation. The linker consists of a non-toxic low molecular
      weight polyethyleneimine (PEI) backbone conjugated with multiple hydrazide groups
      that can aggregate cells within 30 min by reacting with the aldehyde handles on
      the chemically modified cell-surface glycoproteins. The cells in the cellular
      aggregates proliferated; and maintained the cortical actin distribution of the 3D
      cell morphology while non-aggregated cells died over 7 days of suspension
      culture. The aggregates lost distinguishable cell-cell boundaries within 3 days;
      and the ECM fibers became visible around cells from day 3 onwards while the inter
      cellular polymeric linker disappeared from the cell surfaces over time. The
      transient inter-cellular polymeric linker can be useful for forming 3D cellular
      and tissue constructs without bulk biomaterials or extensive network of
      engineered ECM for various applications.

PMID- 17512585
TI  - A rate-insensitive linear viscoelastic model for soft tissues.
AB  - It is well known that many biological soft tissues behave as viscoelastic
      materials with hysteresis curves being nearly independent of strain rate when
      loading frequency is varied over a large range. In this work, the rate
      insensitive feature of biological materials is taken into account by a
      generalized Maxwell model. To minimize the number of model parameters, it is
      assumed that the characteristic frequencies of Maxwell elements form a geometric
      series. As a result, the model is characterized by five material constants:
      micro(0), tau, m, rho and beta, where micro(0) is the relaxed elastic modulus,
      tau the characteristic relaxation time, m the number of Maxwell elements, rho the
      gap between characteristic frequencies, and beta=micro(1)/micro(0) with micro(1)
      being the elastic modulus of the Maxwell body that has relaxation time tau. The
      physical basis of the model is motivated by the microstructural architecture of
      typical soft tissues. The novel model shows excellent fit of relaxation data on
      the canine aorta and captures the salient features of vascular viscoelasticity
      with significantly fewer model parameters.

PMID- 17512587
TI  - MTHFR polymorphisms' influence on outcome and toxicity in acute lymphoblastic
      leukemia patients.
AB  - Recently the influence of polymorphisms of different genes involved in metabolism
      of chemoterapic agents have been studied especially in childhood acute
      lymphoblastic leukemia (ALL). We evaluated the influence of C677T and A1298C
      methylenetetrahydrofolate reductase (MTHFR) polymorphisms on time to relapse and
      survival and on methotrexate (MTX) toxicity in 82 ALL adult patients. Relapse
      free survival and event free survival between homozygous wild-type and variant
      patients in both polymorphisms were not significantly different. However, we
      observed an association between 677TT variant and survival in a subset of ALL
      patients homogenously treated with MTX-based maintenance (p=0.02). In the same
      subgroup we confirmed the role of 677TT variant on toxicity during MTX treatment
      (p=0.003).

PMID- 17512588
TI  - Nelarabine activity in acute biphenotypic leukemia.

PMID- 17512586
TI  - Neuronal calcium channels: splicing for optimal performance.
AB  - Calcium ion channels coordinate an astounding number of cellular functions.
      Surprisingly, only 10 Ca(V)alpha(1) subunit genes encode the structural cores of
      all voltage-gated calcium channels. What mechanisms exist to modify the structure
      of calcium channels and optimize their coupling to the rich spectrum of cellular
      functions? Growing evidence points to the contribution of post-translational
      alternative processing of calcium channel RNA as the main mechanism for expanding
      the functional potential of this important gene family. Alternative splicing of
      RNA is essential during neuronal development where fine adjustments in protein
      signaling promote and inhibit cell-cell interactions and underlie axonal
      guidance. However, attributing a specific functional role to an individual splice
      isoform or splice site has been difficult. In this regard, studies of ion
      channels are advantageous because their function can be monitored with precision,
      allowing even subtle changes in channel activity to be detected. Such studies are
      especially insightful when coupled with information about isoform expression
      patterns and cellular localization. In this paper, we focus on two sites of
      alternative splicing in the N-type calcium channel Ca(V)2.2 gene. We first
      describe cassette exon 18a that encodes a 21 amino acid segment in the II-III
      intracellular loop region of Ca(V)2.2. Here, we show that e18a is upregulated in
      the nervous system during development. We discuss these new data in light of our
      previous reports showing that e18a protects the N-type channel from cumulative
      inactivation. Second, we discuss our published data on exons e37a and e37b, which
      encode 32 amino acids in the intracellular C-terminus of Ca(V)2.2. These exons
      are expressed in a mutually exclusive manner. Exon e37a-containing Ca(V)2.2 mRNAs
      and their resultant channels express at higher density in dorsal root ganglia
      and, as we showed recently, e37a increases N-type channel sensitivity to G
      protein-mediated inhibition, as compared to generic e37b-containing N-type
      channels.

PMID- 17512589
TI  - International standardisation of quantitative real-time RT-PCR for BCR-ABL.

PMID- 17512590
TI  - Rapid detection of mutagens accumulated in plant tissues using a novel Vibrio
      harveyi mutagenicity assay.
AB  - Detection of mutagenic pollution in natural environment is difficult as there are
      thousands of known chemical mutagens, and they have mutagenic effects usually at
      very low concentrations. Plants are able to accumulate various substances,
      including mutagens, in their tissues. Here, we demonstrate that rapid detection
      of mutagenic activities of compounds accumulated in plant tissues is possible
      using a recently developed microbiological mutagenicity assay, based on induction
      of bioluminescence of a dim mutant of a marine bacterium Vibrio harveyi. Using
      this assay, it was possible to detect mutagenic activity in extracts from
      relatively small amounts of tissues (1.5 g) collected from plants, which were
      cultured in vitro for 30 days in the presence of nano-molar concentrations of
      various chemical mutagens. Moreover, contrary to control samples, cultured in
      vitro without any mutagens, significant mutagenicity was detected in several
      extracts of plant tissues collected from natural environment. The whole procedure
      was as short as 4 h or less.

PMID- 17512591
TI  - Tolerance of the lichen Xanthoria parietina (L.) Th. Fr. to metal stress.
AB  - Comparisons were made between the content of Al, Cd, Cu, Fe, Mn, Pb, Sb and Zn in
      thalli of the lichen Xanthoria parietina and selected physiological processes.
      Assimilation pigments, activity of photosystem II, parietin, reactive substances
      produced using thiobarbituric acid (TBA) and CO(2) gas exchange were measured in
      order to assess tolerance to atmospheric sources of pollution. As expected,
      lichen thalli accumulated high amounts of the measured elements in relation to
      distance from pollution sources in Kosice, Slovak Republic (US Steel factory and
      vehicular traffic in the city center). However, except for TBA reactive
      substances production and to some extent CO(2) gas exchange at the most polluted
      station, none of the tested physiological parameters showed a clear correlation
      between accumulation of elements and physiological damage. This reflected a high
      degree of pollution tolerance in this lichen and corresponded with its high
      abundance in Kosice.

PMID- 17512592
TI  - Binding of alkylphenols and alkylated non-phenolics to rainbow trout
      (Oncorhynchus mykiss) hepatic estrogen receptors.
AB  - Alkylphenols are well-known endocrine disrupters, mediating effects through the
      estrogen receptor (ER). In the present work, the interaction of alkylphenols and
      alkylated non-phenolics with hepatic rainbow trout (Oncorhynchus mykiss) estrogen
      receptors (rtERs) was determined. The role of alkyl chain length and branching,
      substituent position, number of alkylated groups, and the requirement of a
      phenolic ring structure was assessed. The results showed that the rtERs bound
      most alkylphenols, although with 20,000 to 2 million times lower affinity than
      the endogenous estrogen 17beta-estradiol. Mono-substituted alkylphenols with
      moderate (C4-C6) and long (C8 and C12) alkyl chain length in the para position
      exhibited the highest affinity for the rtERs. Substitution with multiple alkyl
      groups, presence of substituents in the ortho- and meta-position, and lack of a
      hydroxyl group on the benzene ring reduced the binding affinity. The rtERs
      resembled the reported binding specificity of the human ER for alkylphenols,
      although some exceptions were identified.

PMID- 17512593
TI  - Immune responses against measles virus in cynomolgus monkeys.
AB  - Measles virus (MV) induces profound suppression of the immune response during and
      for weeks after acute infection. On the other hand, virus-specific immune
      responses that mediate viral clearance and confer long-lasting immunity are
      efficiently generated. To investigate this paradox, we studied the immune
      responses to MV using a monkey model of acute measles. Cynomolgus monkeys were
      experimentally infected with wild-type MV (MV-HL) and showed marked leukopenia
      associated with a steady reduction in CD4+ T cell numbers for 18 days post
      inoculation. Transient expression of interferon and IL-6 were observed in the
      serum between 4 and 6 days post-inoculation, and IL-10 levels increased after 11
      days post-inoculation. Interestingly, IL-8 showed a three-peak increase that
      correlated with an increase in neutrophils. A non-human primate model of measles
      allows the early immune response against MV to be studied in more detail.

PMID- 17512594
TI  - Daily intake of 4-nonylphenol in Taiwanese.
AB  - Alkylphenol polyethoxylates (APEO), alkylphenols combined with ethylene oxide,
      are a class of nonionic surfactants. APEO have been widely used for industrial,
      agricultural and household applications, and are biodegraded to more persistent
      and estrogen-active products, namely, nonylphenol (NP), octylphenol (OP),
      butylphenol (BP), nonylphenol monoethoxylate (NP(1)EO) and nonylphenol
      diethoxylate (NP(2)EO). This study determined NP levels in commonly consumed
      foodstuffs to assess daily intake of NP in a Taiwanese population. This study
      analyzes 318 of samples from 25 types of commonly consumed foodstuffs in
      northern, central, southern and eastern regions of Taiwan and estimates daily
      intake of NP in 466 subjects. Moreover, daily NP intake for 3915 additional
      subjects was estimated by analyzing data from the Nutrition and health survey in
      Taiwan (NAHSIT). The foodstuff samples were analyzed for five alkylphenol
      compounds simultaneously by HPLC with fluorescence detection. Additionally, the
      average compositions of typical foods consumed in Taiwan were investigated. In
      combination with alkylphenol levels in these foodstuffs, daily intake of NP in
      Taiwanese was calculated. The average daily intake of NP for the 466 subjects was
      28.04+/-25.32 microg/day. Estimated daily intake of NP, based on NP levels in
      this study as well as the NAHSIT data, was 31.40 microg/day. Rice was the most
      commonly consumed source of NP, the proportion was 21.46% among daily intake of
      NP and the following were aquatic products and livestock, which percentage were
      17.97% and 17.38%, respectively. Additionally, oysters had the highest NP levels
      (235.8+/-90.7 ng/g) in four regions of Taiwan, followed by salmon (123.8+/-116.2
      ng/g). This study suggested that the average daily NP intake in Taiwan is 4-fold
      and 8.5-fold higher than daily intake in Germany and New Zealand, respectively
      and rice was the major source of NP intake.

PMID- 17512595
TI  - The C-terminal pentapeptide of LHRH is a dominant B cell epitope with antigenic
      and biological function.
AB  - Luteinizing hormone releasing hormone (LHRH) has been intensively studied as a
      target for the control of fertility and hormone dependent cancers. In most
      studies a decapeptide, EHWSYGLRPG, which is identical to the native LHRH
      sequence, has been used. In this study we investigated whether short sequences of
      LHRH could retain immunogenic and antigenic properties and be employed in a
      vaccine preparation. Our results show that the C-terminal five-residue peptide
      (LHRH(6-10)) of LHRH was able to inhibit the binding of anti-LHRH(1-10) antisera
      to LHRH(1-10) in an inhibition ELISA. A totally synthetic peptide vaccine
      incorporating LHRH(6-10) also elicited a strong anti-LHRH antibody response and
      prevented mice from becoming pregnant in fertility trials. The primary immune
      response elicited by a peptide vaccine based on LHRH(1-10) could be boosted with
      LHRH(6-10). Finally, an antigen system comprising of biotinylated LHRH(6-10)
      bound to streptavidin-coated plates was capable of discriminating between anti
      LHRH antibodies present in fertile and non-fertile mice. This study demonstrates
      that LHRH(6-10) retains immunogenic and antigenic properties and also discerns
      antibody specificities associated with reproductive competence.

PMID- 17512596
TI  - Sea bass (Dicentrarchus labrax) invariant chain and class II major
      histocompatibility complex: sequencing and structural analysis using 3D homology
      modelling.
AB  - The present manuscript reports for the first time the sequencing and
      characterisation of sea bass (sb) MHCII alpha and beta chains and Ii chain cDNAs
      as well as their expression analysis under resting state. 3D homology modelling,
      using crystal structures from mammalian orthologues, has been used to illustrate
      and support putative structural homologies of the sea bass counterparts. The sbIi
      cDNA consists of 96 bp of 5'-UTR, a 843 bp open reading frame (ORF) and 899 bp of
      3'-UTR including a canonical polyadenylation signal 16 nucleotides before the
      polyadenylation tail. The ORF was translated into a 280 amino acid sequence, in
      which all characteristic domains found in the Ii p41 human form could be
      identified, including the cytoplasmic N-terminus domain, the transmembrane (TM)
      region, the CLIP domain, the trimerization domain and the thyroglobulin (Tg) type
      I domain. The trimerization and Tg domains of sbIi were successfully modelled
      using the human counterparts as templates. Four different sequences of each class
      II alpha and beta MHCII were obtained from a single fish, apparently not derived
      from a single locus. All the characteristic features of the MHCII chain structure
      could be identified in the predicted ORF of sea bass alpha and beta sequences,
      consisting of leader peptide (LP), alpha1/beta1 and alpha2/beta2 domains,
      connecting peptide and TM and cytoplasmic regions. Furthermore, independently of
      the HLA-DR crystal structure used as template in homology modelling, a similar
      predicted 3D structure and trimeric quaternary architecture was obtained for
      sbMHC, with major deviations occurring only within the sea bass MHCII alpha1
      domain.

PMID- 17512597
TI  - Is it worth reoperating on macular holes?
AB  - OBJECTIVE: To evaluate the visual outcome after a second surgical attempt to
      close idiopathic full-thickness macular holes (FTMH) in patients who underwent
      unsuccessful primary surgery and in patients with reopened FTMHs. DESIGN:
      Retrospective single-center case series. PARTICIPANTS: Five hundred thirty-two
      patients underwent surgery for FTMH in St. Paul's Eye Unit, Liverpool, United
      Kingdom, between March, 1995, and March, 2005. Fifty-one patients had unclosed
      FTMHs (unclosed group) and 21 patients had reopened FTMHs after initially
      successful surgery (reopened group). METHODS: All patients underwent a second
      pars plana vitrectomy. Autologous platelet concentrate and perfluoropropane
      endotamponade were used. Internal limiting membrane peeling was carried out in
      selected cases. Patients were instructed to maintain a face-down position for 2
      weeks after the surgery. MAIN OUTCOME MEASURES: Anatomic and visual results.
      RESULTS: All patients in the reopened group and 76% of patients in the unclosed
      group achieved successfully closure of the FTMH after the second surgery. Mean
      decimal Snellen visual acuity (VA; +/-standard deviation [SD]) before the second
      surgery was 0.14+/-0.10 (range, 0.01-0.33) in the reopened group and 0.10+/-0.07
      (range, hand movements [HM]-0.33) in the unclosed group. The best VA was achieved
      after cataract surgery; the mean best VA (+/-SD) in the reopened group was 0.42+/
      0.31 (range, 0.05-1) and in the unclosed group was 0.19+/-0.14 (range, HM-0.66).
      CONCLUSIONS: Reoperating on reopened FTMH resulted in 100% anatomic closure and
      significant improvement in vision. In contrast, reoperating on patients with
      initially unsuccessful surgery resulted a lower anatomic closure rate and
      relatively poor final vision even if their macular holes were closed
      successfully. This information may help surgeons and patients decide whether to
      undertake a second operation.

PMID- 17512598
TI  - Short-term effect of antibiotic control policy on the usage patterns and cost of
      antimicrobials, mortality, nosocomial infection rates and antibacterial
      resistance.
AB  - OBJECTIVES: In 2003 Turkish government released a new budget application
      instruction for regulating the usage of parenteral antibiotics inside and outside
      of the hospitals. In this study it was aimed to evaluate the effect of this
      instruction on the overall usage of restricted antibiotics, their cost, overall
      mortality, bacterial resistance patterns and nosocomial infection rates in
      intensive care units (ICUs) of our setting for March-October 2002 and March
      October 2003 periods. METHODS AND RESULTS: Overall daily defined dose/1000
      patients/day of restricted drugs decreased, whereas unrestricted drugs increased
      significantly after the instruction. The cost of all analysed drugs in 2003
      period was 540,303USD (-19.6%) less than 2002 period. Nosocomial infection rates
      in ICUs decreased significantly (p<0.05). When all microbiologically confirmed
      nosocomial bacteremia cases during the study period were analysed,
      amoxycilline/clavulanate, ciprofloxacin, cefuroxime, cefotaxime,
      piperacilline/tazobactam resistance and ESBL rate in Klebsiella pneumoniae
      decreased significantly (p<0.05). Amikacin resistance in Escherichia coli and
      Acinetobacter baumannii increased significantly (p<0.05). CONCLUSION: Antibiotic
      control is one of the most important and significant ways to save money, and to
      prevent antibacterial resistance.

PMID- 17512599
TI  - Effects of exercise training on the cardiovascular system: pharmacological
      approaches.
AB  - Physical exercise promotes beneficial health effects by preventing or reducing
      the deleterious effects of pathological conditions, such as arterial
      hypertension, coronary artery disease, atherosclerosis, diabetes mellitus,
      osteoporosis, Parkinson's disease, and Alzheimer disease. Human movement studies
      are becoming an emerging science in the epidemiological area and public health. A
      great number of studies have shown that exercise training, in general, reduces
      sympathetic activity and/or increases parasympathetic tonus either in human or
      laboratory animals. Alterations in autonomic nervous system have been correlated
      with reduction in heart rate (resting bradycardia) and blood pressure, either in
      normotensive or hypertensive subjects. However, the underlying mechanisms by
      which physical exercise produce bradycardia and reduces blood pressure has not
      been fully understood. Pharmacological studies have particularly contributed to
      the comprehension of the role of receptor and transduction signaling pathways on
      the heart and blood vessels in response to exercise training. This review
      summarizes and examines the data from studies using animal models and human to
      determine the effect of exercise training on the cardiovascular system.

PMID- 17512600
TI  - Therapy of pulmonary hypertension in neonates and infants.
AB  - Pulmonary hypertension (PH) in newborns and infants can present in its idiopathic
      form or complicate a long list of other diseases. Most of these conditions are
      either pulmonary or cardiovascular in origin. In the present review our current
      knowledge regarding pathophysiology, structural changes, diagnosis, and available
      treatment options for PH in the age group below 1 year of age is summarized. New
      treatment options available in adults including endothelin receptor antagonists
      (ETRA) and phosphodiesterase (PDE) inhibitors are presented and the need for
      randomized controlled trials in newborns and infants is emphasized. Future
      candidates for pharmacotherapy of PH in infants include among others vasoactive
      intestinal polypeptide (VIP), PDE-3 and PDE-4 inhibitors, hydroxymethylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors, and adrenomedullin (ADM).

PMID- 17512601
TI  - Possible utilization of in vitro synthesized mRNAs specifically expressed in
      certain tissues as standards for quantitative evaluation of the results of
      microarray analysis.
AB  - To examine the possible usefulness of in vitro synthesized RNA as standards in
      microarray analysis, we prepared full-length mRNAs encoded by 3 rat metabolic
      genes for heart/muscle type carnitine palmitoyltransferase I (M-CPTI), uncoupling
      protein (UCP1), and heart/muscle type fatty acid-binding protein (H-FABP).
      Artificial RNA samples were prepared by adding known amounts of these synthetic
      mRNAs to total RNA from rat liver, and transcript levels of various genes were
      compared between the prepared artificial RNA samples and total RNA samples of rat
      liver by using an Agilent oligo microarray system. Upon the addition of these
      synthetic RNAs, signals from the DNA spots corresponding to these 3 genes were
      elevated, but those from the DNA spots representing other genes were not markedly
      influenced. Using the ratio of the increase in signal intensity of DNA spot to
      the amount of added RNA, we estimated the expression levels of several genes and
      compared them with the absolute expression levels determined by calibrated
      Northern analysis. As a result, the absolute transcript levels of 3 genes
      encoding acidic ribosomal phosphoprotein P0, type-1 voltage-dependent anion
      channel (VDAC1), and type-2 glucose transporter (GLUT2) were successfully
      estimated by this procedure. Furthermore, genes specifically expressed in certain
      tissues such as UCP1 were concluded to be good candidates as standards for use in
      microarray analysis.

PMID- 17512602
TI  - Electrophysiological and pharmacological validation of vagal afferent fiber type
      of neurons enzymatically isolated from rat nodose ganglia.
AB  - An unavoidable consequence of enzymatic dispersion of sensory neurons from intact
      ganglia is loss of the axon and thus the ability to classify afferent fiber type
      based upon conduction velocity (CV). An intact rat nodose ganglion preparation
      was used to randomly sample neurons (n=76) using the patch clamp technique.
      Reliable electrophysiological and chemophysiological correlates of afferent fiber
      type were established for use with isolated neuron preparations. Myelinated
      afferents (approximately 25%) formed two groups exhibiting strikingly different
      functional profiles. One group (n=10) exhibited CVs in excess of 10 m/s and
      narrow (<1 ms) action potentials (APs) while the other (n=9) had CVs as low as
      4m/s and broad (>2 ms) APs that closely approximated those identified as
      unmyelinated afferents (n=57) with CVs less than 1m/s. A cluster analysis of
      select measures from the AP waveforms strongly correlated with CV, producing
      three statistically unique populations (p<0.05). These groupings aligned with our
      earlier hypothesis (Jin et al., 2004) that a differential sensitivity to the
      selective purinergic and vanilloid receptor agonists can be used as reliable
      pharmacological indicators of vagal afferent fiber type. These metrics were
      further validated using an even larger population of isolated (n=240) nodose
      neurons. Collectively, these indicators of afferent fiber type can be used to
      provide valuable insight concerning the relavence of isolated cellular
      observations to integrated afferent function of visceral organ systems.

PMID- 17512603
TI  - Automated spike sorting using density grid contour clustering and subtractive
      waveform decomposition.
AB  - In multiple cell recordings identifying the number of neurons and assigning each
      action potential to a particular source, commonly referred to as 'spike sorting',
      is a highly non-trivial problem. Density grid contour clustering provides a
      computationally efficient way of locating high-density regions of arbitrary shape
      in low-dimensional space. When applied to waveforms projected onto their first
      two principal components, the algorithm allows the extraction of templates that
      provide high-dimensional reference points that can be used to perform accurate
      spike sorting. Template matching using subtractive waveform decomposition can
      locate these templates in waveform samples despite the influence of noise,
      spurious threshold crossing and waveform overlap. Tests with a large synthetic
      dataset incorporating realistic challenges faced during spike sorting (including
      overlapping and phase-shifted spikes) reveal that this strategy can consistently
      yield results with less than 6% false positives and false negatives (and less
      than 2% for high signal-to-noise ratios) at processing speeds exceeding those
      previously reported for similar algorithms by more than an order of magnitude.

PMID- 17512604
TI  - Determination of cerebrospinal fluid concentrations of arginine and
      dimethylarginines in patients with subarachnoid haemorrhage.
AB  - Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine
      (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), are assumed to be
      related to delayed vasospasm after subarachnoid haemorrhage (SAH). However, data
      on CSF concentrations of L-arginine, ADMA and its structural isomer symmetric
      dimethylarginine (SDMA) are very sparse in humans. We here present a new
      hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS-MS)
      method for the precise determination of these substances in CSF. The method
      requires only minimal sample preparation and features isotope labeled internal
      standards. First data of patients with SAH showed that on the day of admission
      CSF concentration values of L-arginine and ADMA were not significantly different
      from controls, but increased markedly during the course of the hospital stay. The
      decrease of the L-arginine to ADMA ratio points to a progressive impairment of
      the NO production rate in the brain after SAH which is confirmed by a
      simultaneous decrease in nitrate and nitrite concentrations in CSF.

PMID- 17512605
TI  - Spatial distribution of human neocortical neurons and glial cells according to
      sex and age measured by the saucer method.
AB  - A new stereological probe, the saucer, was used for estimating three-dimensional
      (3D) spatial distributions of particles around particles. The advantages of the
      saucer include that the measurements and the results are in 3D and the size and
      design of the probe enables the investigator to sample a proportion of a suitable
      size to have a reasonable relationship between workload and the information
      obtained. In this paper the method is used on vertical sections to investigate
      the spatial distribution of astrocytes, oligodendrocytes, microglial cells,
      endothelial cells and secondary neurons around primary neurons in the human
      neocortex (divided into frontal-, temporal-, parietal- and occipital cortex) of
      young and old subjects free of neurological or psychological disease to test if
      age and gender has any influence on the cell distribution in human neocortex.
      Plots of the spatial distribution of the densities of all cell types did not show
      any difference between women and men and no difference between brains of young
      and old subjects. Thus it is concluded that in this small study the spatial
      distribution of the densities of the different types of cells in brains from
      individuals free of neurological disorders was independent of age and gender.

PMID- 17512606
TI  - Preschool Bipolar Disorder: Brazilian children case reports.
AB  - OBJECTIVE: This study describes the clinical phenomenology and family history of
      preschool age onset Bipolar Disorder (BD). METHODS: Eight children and
      adolescents out of 118 cases (6.78%), both genders, meeting current DSM-IV
      criteria diagnosis of BD were described. The clinical assessment, CBCL, DICA-IV
      and CGAS were performed directly with each patient and their parents. RESULTS:
      Most (87.5%) presented classical symptoms of mania: euphoria, grandiosity,
      irritability, psychomotor agitation and agitated sleep or, in the same
      proportion, sleeplessness. Hyperactivity and increase of energy were found in all
      eight cases. The clinical course varied from a rapid, ultra-rapid, ultradian
      cycle to a continued pattern. Five out of eight children (62.5%) presented
      aggressiveness toward others and one deliberate self-harm. Most (87.5%) had
      psychiatric family history. The average number of medications used during their
      life was 4.5 drugs. LIMITATION: The small sample and retrospective reports of the
      first manic symptoms in three of the cases (cases V, VI and VII). CONCLUSION: An
      important incidence of classical manic features was found in very young children.
      The clinical course tended to be continuous, and preschool BD seems to have a
      strong association with affective disorder family history.

PMID- 17512607
TI  - Effect of comorbid anxiety on treatment response in bipolar depression.
AB  - BACKGROUND: This secondary analysis from a randomized double-blind study of acute
      bipolar depression compared olanzapine monotherapy, olanzapine-fluoxetine
      combination (OFC) and placebo in patients with or without comorbid anxiety.
      METHODS: Patients with bipolar disorder and a current depressive episode received
      olanzapine (5-20 mg/day), OFC (6/25, 6/50, or 12/50 mg/day), or placebo in an 8
      week trial. Two populations were defined: comorbid (Hamilton Anxiety Rating
      Scale, HAM-A > or =18) or non-comorbid (HAM-A <18) anxiety. Changes in Montgomery
      Asberg Depression Rating Scale (MADRS) and HAM-A total scores, and rates of
      response (> or =50% decrease from baseline to endpoint) and remission (MADRS < or
      =12 or HAM-A < or =7) were analyzed. RESULTS: Baseline MADRS and YMRS scores were
      significantly higher in patients with comorbid anxiety relative to those without.
      Patients without comorbid anxiety were more likely to achieve MADRS response and
      remission than those with comorbid anxiety (relative risk, RR: 1.21 and 1.29,
      respectively). Patients with comorbid anxiety had greater rates of response and
      remission with olanzapine and OFC relative to placebo (response RR:1.45 and 2.14;
      remission RR:1.96 and 2.32, respectively). Response and remission rates on the
      HAM-A scale were greater for OFC relative to placebo (RR: 2.00 and 3.20). Weight
      gain was greater for olanzapine (2.59+/-3.24 kg) and OFC (2.79+/-3.23 kg)
      relative to placebo, as were baseline to endpoint changes in cholesterol levels
      (6+/-31 and 10+/-67 mg/dL, respectively). CONCLUSIONS: Comorbid anxiety symptoms
      in patients with bipolar depression have a negative impact on treatment outcome.
      Olanzapine and, to a greater extent, olanzapine-fluoxetine combination were
      effective in reducing both depressive and anxiety symptoms in these patients. The
      significantly greater changes in weight, glucose and cholesterol parameters
      observed in the olanzapine and olanzapine-fluoxetine combination groups should be
      entered into the risk-benefit assessment in determining appropriate treatment
      options for these patients.

PMID- 17512608
TI  - The xMAP technique can be used for detection of the inflammatory cytokines IL
      1beta, IL-6 and TNF-alpha in bovine samples.
AB  - Infectious diseases can cause large health problems in cattle. The infections
      cause an acute inflammatory response, mediated by pro-inflammatory cytokines such
      as IL-1beta, IL-6 and TNF-alpha. By mapping the pattern of cytokines during
      inflammations, valuable information about the course of an infection is gained.
      The aim of the present study was to evaluate a particle-based flow cytometric
      method, the xMAP technique, using ovine/bovine reagents, for quantification of IL
      1beta, IL-6 and TNF-alpha, for application in studies on ruminant infectious
      diseases with emphasis on bovine milk and plasma samples. Singleplex, duplex and
      triplex xMAP assays were evaluated, and limits of detection (LODs) as well as
      intra- and inter-assay variabilities were determined for each assay. Cross
      reactivity between reagents in multiplex assays was also tested. In addition,
      presence of cytokines in milk and plasma samples from healthy and mastitic cows
      was studied. The LODs were significantly lower for singleplex xMAP assays than
      for duplex and triplex assays. In singleplex assays, the LODs were 0.08, 0.2 and
      0.5 ng/ml, for IL-1beta, IL-6 and TNF-alpha, respectively. Corresponding LODs in
      triplex assays were 2.0, 6.5 and 3.5 ng/ml. Data indicate that the linear ranges
      of the multiplex assays were narrower than in singleplex assays. The intra-assay
      coefficients of variation were < or =10.7% for singleplex assays, while they
      ranged from 6.2 to 23.2% in the triplex assay. The inter-assay variance ranged
      from 5.1 to 35.8% in singleplex assays, and from 8.8 to 78.4% in triplex assays.
      Cross-reactivity between reagents was not observed, and all three cytokines were
      detected in bovine milk and plasma samples collected from cows with clinical
      mastitis. In conclusion, our results show that the xMAP technique can be used for
      quantification of IL-1beta, IL-6 and TNF-alpha in bovine samples, and that
      further work is required to optimize the multiplex assays.

PMID- 17512609
TI  - TNFalpha-induced sickness behavior in mice with functional 55 kD TNF receptors is
      blocked by central IGF-I.
AB  - A variety of pathogenic insults cause synthesis of tumor necrosis factor
      (TNF)alpha in the brain, resulting in sickness behavior. Here we used TNF
      receptor (TNF-R)2-deficient and wild-type mice to demonstrate that the reduction
      in social exploration of a novel juvenile, the increase in immobility and the
      loss of body weight caused by central TNFalpha (i.c.v., 50 ng/mouse) are blocked
      by central pre-treatment with the multifunctional peptide, insulin-like growth
      factor (IGF-I; i.c.v., 300 ng/mouse). These results establish that sickness
      behavior induced by central TNFalpha via the TNF-R1 (p55) is directly opposed by
      IGF-I in the brain.

PMID- 17512610
TI  - Clinical and MRI correlates of autoreactive antibodies in multiple sclerosis
      patients.
AB  - BACKGROUND: Autoreactive antibodies (ARAB) occur more frequently in patients with
      multiple sclerosis (MS) than in general population and the presence of these
      antibodies often causes uncertainty regarding the disease course, response to
      therapy and the diagnosis of MS. METHODS: Retrospective analyses of the ARAB,
      clinical and MRI data of a consecutive patient cohort of MS and clinically
      isolated syndrome (CIS) patients were conducted. The patients were evaluated for
      an extensive panel that included various subtypes of antiphospholipid antibody
      (APLA) including anti-phosphatidylethanolamine (APE), anti-phosphatidylserine
      (APS), anti-beta-2-glycoprotein-1 (ABGP), anti-cardiolipin (ACA), and several
      other ARAB such as antinuclear antibody (ANA), anti-neutrophilic cytoplasmic
      antibodies (ANCA), anti-thyroid peroxidase antibodies (ATA), anti-SS-A, and anti
      SS-B antibodies. Quantitative MRI analysis was performed in a subgroup of MS
      patients measuring T2-lesion volume (LV), T1 black hole LV and brain parenchymal
      fraction (BPF). RESULTS: A total of 137 patients (mean age 44.7, 84% female) with
      either MS (n=111; age: mean 46.5+/-S.D. 10.3 years; disease duration: mean 13.0+/
      S.D. 10.4 years; EDSS: mean 3.2+/-S.D. 1.9) or CIS (n=26; age: mean 37.7+/-S.D.
      7.8 years; disease duration: mean 1.3+/-S.D. 1.1 years; EDSS: mean 1.0+/-S.D.
      0.7) were enrolled. Among MS patients, 82 were RRMS, 26 SPMS, and 3 had PPMS.
      Seventy-seven (69%) of MS patients showed presence of one or more ARAB. The
      proportion of MS patients with APLA was 55% (61 patients); IgM subtype was most
      frequent. Co-occurrence of ACA and APE was more frequent in SPMS as compared to
      RRMS (15.4% vs. 1.2%, p=0.012). The proportion of CIS patients with ARAB was 75%
      with IgM subtype being the most frequent. However, the ARAB in majority of CIS
      patients (9 out of 14, 64%) were transient on repeated testing. In a subgroup of
      62 MS patients, quantitative MRI analysis showed significantly higher T2-LV in
      patients with positive APLA (15.1 ml for APLA positive vs. 6.75 ml for APLA
      negative) after correcting for the disease duration (p=0.048). The patients with
      ATA also had significantly higher T2-LV after correction for disease duration
      (19.0 ml vs.8.5, p=0.044). CONCLUSIONS: ARAB were present in more than two thirds
      of MS and CIS patients although most of APLA in CIS were transient. The presence
      of APLA in MS patients was associated with higher T2-LV.

PMID- 17512612
TI  - Comparison of upper and lower lip muscle activity between stutterers and fluent
      speakers.
AB  - OBJECTIVE: There is a widespread clinical view that stuttering is associated with
      high levels of muscles activity. The proposal of this research was to compare
      stutterers and fluent speakers with respect to the electromyographic activity of
      the upper and lower lip muscles. METHODS: Ten individuals who stutter and 10
      fluent speakers (control group) paired by gender and age were studied (mean age:
      13.4 years). Groups were defined by the speech sample analysis of the ABFW
      Language Test. A K6-I EMG (Myo-tronics Co., Seattle, WA, USA) with double
      disposable silver electrodes (Duotrodes, Myo-tronics Co., Seattle, WA) being used
      in order to analyze lip muscle activity. The clinical conditions investigated
      were movements during speech, orofacial non-speech tasks, and rest.
      Electromyographic data were normalized by lip pursing activity. The non
      parametric Mann-Whitney test was used for the comparison of speech fluency
      profile, and the Student t-test for independent samples for group comparison
      regarding electromyographic data. RESULTS: There was a statistically significant
      difference between groups regarding speech fluency profile and upper lip activity
      in the following conditions: lip lateralization to the right and to the left and
      rest before exercises (P<0.05). There was no significant difference between
      groups regarding lower lip activity (P>0.05). CONCLUSION: The EMG activity of the
      upper lip muscle in the group with stuttering was significantly lower than in the
      control group in some of the clinical conditions analyzed. There was no
      significant difference between groups regarding the lower lip muscle. The
      subjects who stutter did not present higher levels of muscle activity in lip
      muscles than fluent speakers.

PMID- 17512611
TI  - Characterization of a severe parenchymal phenotype of experimental autoimmune
      encephalomyelitis in (C57BL6xB10.PL)F1 mice.
AB  - We here describe a novel CD4 T cell adoptive transfer model of severe
      experimental autoimmune encephalomyelitis in (C57BL6xB10.PL)F1 mice. This FI
      cross developed severe disease characterized by extensive parenchymal spinal cord
      and brain periventricular white matter infiltrates. In contrast, B10.PL mice
      developed mild disease characterized by meningeal predominant infiltrates. As
      determined by cDNA microarray and quantitative real time PCR expression analysis,
      histologic and flow cytometry analysis of inflammatory infiltrates, and
      attenuation of disease in class I-deficient and CD8-depleted F1 mice; this severe
      disease phenotype appears to be regulated by CNS infiltration of CD8 T
      lymphocytes early in the disease course.

PMID- 17512613
TI  - Speech and language development in a population of Swedish hearing-impaired pre
      school children, a cross-sectional study.
AB  - OBJECTIVE: There is little information on speech and language development in pre
      school children with mild, moderate or severe hearing impairment. The primary aim
      of the study is to establish a reference material for clinical use covering
      various aspects of speech and language functions and to relate test values to
      pure tone audiograms and parents' judgement of their children's hearing and
      language abilities. METHODS: Nine speech and language tests were applied or
      modified, both classical tests and newly developed tests. Ninety-seven children
      with normal hearing and 156 with hearing impairment were tested. Hearing was 80
      dB HL PTA or better in the best ear. Swedish was their strongest language. None
      had any additional diagnosed major handicaps. The children were 4-6 years of age.
      The material was divided into 10 categories of hearing impairment, 5 conductive
      and 5 sensorineural: unilateral; bilateral 0-20; 21-40; 41-60; 61-80 dB HL PTA.
      The tests, selected on the basis of a three component language model, are phoneme
      discrimination; rhyme matching; Peabody Picture Vocabulary Test (PPVT-III, word
      perception); Test for Reception of Grammar (TROG, grammar perception); prosodic
      phrase focus; rhyme construction; Word Finding Vocabulary Test (word production);
      Action Picture Test (grammar production); oral motor test. RESULTS: Only
      categories with sensorineural loss showed significant differences from normal.
      Word production showed the most marked delay for 21-40 dB HL: 5 and 6 years
      p<0.01; for 41-60 dB: 4 years p<0.01 and 6 years p<0.01 and 61-80 dB: 5 years
      p<0.05. Phoneme discrimination 21-40 dB HL: 6 years p<0.05; 41-60 dB: 4 years
      p<0.01; 61-80 dB: 4 years p<0.001, 5 years p<0.001. Rhyme matching: no
      significant difference as compared to normal data. Word perception: sensorineural
      41-60 dB HL: 6 years p<0.05; 61-80 dB: 4 years p<0.05; 5 years p<0.01. Grammar
      perception: sensorineural 41-60 dB HL: 6 years p<0.05; 61-80 dB: 5 years p<0.05.
      Prosodic phrase focus: 41-60 dB HL: 5 years p<0.01. Rhyme construction: 41-60 dB
      HL: 4 years p<0.05. Grammar production: 61-80 dB HL: 5 years p<0.01. Oral motor
      function: no differences. The Word production test showed a 1.5-2 years delay for
      sensorineural impairment 41-80 dB HL through 4-6 years of age. There were no
      differences between hearing-impaired boys and girls. Extended data for the
      screening test [E. Borg, A. Risberg, B. McAllister, B.M. Undemar, G. Edquist,
      A.C. Reinholdsson, et al., Language development in hearing-impaired children.
      Establishment of a reference material for a "Language test for hearing-impaired
      children", Int. J. Pediatr. Otorhinolaryngol. 65 (2002) 15-26] are presented.
      CONCLUSIONS: Reference values for expected speech and language development are
      presented that cover nearly 60% of the studied population. The effect of the
      peripheral hearing impairment is compensated for in many children with hearing
      impairment up to 60 dB HL. Above that degree of impairment, language delay is
      more pronounced, probably due to a loss of acuity. The importance of central
      cognitive functions, speech reading and signing for compensation of peripheral
      limitations is pointed out.

PMID- 17512614
TI  - Interactions of macrophages with probiotic bacteria lead to increased antiviral
      response against vesicular stomatitis virus.
AB  - Macrophages are an important cellular component of the innate immune system and
      are normally rapidly recruited and/or activated at the site of virus infection.
      They can participate in the antiviral response by killing infected cells, by
      producing antiviral cytokines such as nitric oxide and by producing chemokines
      and immunoregulatory cytokines that enable the adaptive immune response to
      recognize infected cells and perform antiviral effector functions. Probiotics, as
      a part of the normal gut intestinal flora, are important in supporting a
      functional yet balanced immune system. Improving our understanding of their role
      in the activation of macrophages and their stimulation of proinflammatory
      cytokine production in early viral infection was the main goal of this study. Our
      in vitro model study showed that probiotic bacteria, either from the species
      Lactobacillus or Bifidobacteria have the ability to decrease viral infection by
      establishing the antiviral state in macrophages, by production of NO and
      inflammatory cytokines such as interleukin 6 and interferon-gamma. These effects
      correlated with the mitochondrial activity of infected macrophages, therefore,
      the measurements of mitochondrial dehydrogenases activity could be implied as the
      first indicator of potential inhibitory effects of the probiotics on virus
      replication. The interactions between probiotic bacteria, macrophages and
      vesicular stomatitis virus (VSV), markedly depended on the bacterial strain
      studied.

PMID- 17512615
TI  - Neural substrates underlying evaluation of pain in actions depicted in words.
AB  - Previous research has shown that evaluation of pain shown in pictures is mediated
      by a cortical circuit consisting of the primary and secondary somatosensory
      cortex (SI and SII), the anterior cingulate cortex (ACC), and the insula. SI and
      SII subserve the sensory-discriminative component of pain processing whereas ACC
      and the insula mediate the affective-motivational aspect of pain processing. The
      current work investigated the neural correlates of evaluation of pain depicted in
      words. Subjects were scanned using functional magnetic resonance imaging (fMRI)
      while reading words or phrases depicting painful or neutral actions. Subjects
      were asked to rate pain intensity of the painful actions depicted in words or
      counting the number of Chinese characters in the words. Relative to the counting
      task, rating pain intensity induced activations in SII, the insula, the right
      middle frontal gyrus, the left superior temporal sulcus and the left middle
      occipital gyrus. Our results suggest that both the sensory-discriminative and
      affective-motivational components of the pain matrix are engaged in the
      processing of pain depicted in words.

PMID- 17512616
TI  - Prior morphine experience induces long-term increases in social interest and in
      appetitive behavior for natural reward.
AB  - Brain opioids regulate social emotional responsivity. One neuro-evolutionary
      theory of addiction suggests that exogenous opiates may induce addiction via
      opioid-controlled emotional changes; with the drug eventually fulfilling the need
      for social comfort that is normally provided by endogenous opioids. This view
      predicts that past opiate experience may enduringly alter social responsivity.
      Although the acute social effects of opiates are well known, little evidence is
      available concerning the enduring effects of past opiate experience on social
      motivation aside from copulatory behaviors. This study evaluated the long-term
      effects of 10 daily morphine (10mg/kg/day) or saline injections on social and non
      social motivated behaviors. Following 3 days or 2 weeks drug abstinence, social
      interest, food-seeking, and sexual pursuit were assessed. After 2-weeks opiate
      withdrawal, sexual pursuit and food-seeking behaviors were significantly
      increased. After a shorter 3-day withdrawal, these effects were not seen.
      Importantly, social interest was consistently magnified, even after short-term 3
      day opiate withdrawal, and it was magnified more than sexual or food pursuit.
      These findings indicate that the incentive for social and non-social natural
      rewards were increased following withdrawal from intermittent opiate treatment,
      but that different morphine-induced neuroadaptations may regulate their
      expression.

PMID- 17512617
TI  - Functional genomics in Trypanosoma brucei: a collection of vectors for the
      expression of tagged proteins from endogenous and ectopic gene loci.

PMID- 17512618
TI  - Cross-sectional observations of thyroid function in geriatric Mexican outpatients
      with and without dementia.
AB  - This work was aimed at determining and comparing the frequency of abnormal levels
      of thyroid stimulating hormone (TSH) in geriatric outpatients with and without
      dementia. This cross-sectional study enrolled patients, aged 60 years and older
      with or without dementia (established on the basis of DSM-IV-R), from geriatric
      outpatient unit with third level of medical care. Comparisons were between 33
      (34%) patients without dementia versus 26 (58%) with dementia; both among 142
      (24%) randomly selected sample (RSS) from unit's register; and the 101 (89%) in
      the memory-clinic case series (MCCS) of dementia were contrasted with the former.
      MEASUREMENTS: TSH, total/free thyroxine, mini-mental-state examination (MMSE),
      geriatric depression scale (GDS), Hachinski ischemic-score (HIS), and clinical
      data from the patients' charts. In the above order, high TSH was found in 9
      (27.3%, confidence interval (CI)=12.1-42.5%), 6 (23.1%, CI=6.9-46.5%), and 30
      (29.7%, CI=20.8-38.6%), respectively. Low-normal free thyroxine levels
      accompanied 76% of individuals with elevated TSH; in contrast of Gaussian
      distribution of free thyroxine in those with TSH in normal range. In conclusion,
      the high frequency found of hypothyroidism in patients with and without dementia
      warrants further studies. Treatment is only being recommended for patients with
      below range thyroxin levels; while treatment of subclinical hypothyroidism in the
      presence of cognitive decline will be addressed in the forthcoming studies.

PMID- 17512619
TI  - Effect of combined secretagogue/biguanide treatment on mortality in type 2
      diabetic patients with and without ischemic heart disease.
AB  - BACKGROUND: The aim of this investigation was the assessment of the association
      of combined secretagogue/biguanide treatment with mortality in type 2 diabetic
      patients with and without ischemic heart disease (IHD). METHODS: A retrospective
      observational cohort study was performed on a consecutive series of 1108 non
      insulin-treated diabetic outpatients, with a mean follow-up of 28.0+/-6.5 months.
      Information on all-cause mortality was obtained by the City of Florence Registry
      Office. RESULTS: Patients treated with combinations of insulin secretagogues and
      biguanides at enrolment showed a significantly higher yearly mortality rate when
      compared with the rest of the sample (3.6% vs. 6.2% yearly; p<0.05); this was
      confirmed at multivariate analysis (OR [95% CI] 1.618[1.044;2.512]). When
      patients with IHD were analyzed separately, combined therapy was associated with
      a significantly higher mortality (hazard ratio 2.262[1.005;5.102]). Conversely,
      among patients without a previous diagnosis of IHD, a non significant trend
      toward an increase of mortality was observed in those on combined therapy.
      CONCLUSIONS: The present study shows that the increase of mortality associated
      with combinations of biguanides and insulin secretagogues is evident only in
      patients with IHD. It can be speculated that biguanides could enhance the well
      known effects of sulphonylureas on ischemic preconditioning in patients with IHD,
      aggravating the damage determined by ischemia.

PMID- 17512620
TI  - Detecting vulnerable plaque of arteriosclerosis obliterans by multidetector-row
      computed tomography--comparing with VH (virtual histology)-intravascular
      ultrasound.

PMID- 17512621
TI  - Fluorescence activated cell sorting (FACS) using RNAlater to minimize RNA
      degradation and perturbation of mRNA expression from cells involved in initial
      host microbe interactions.
AB  - Host microbe interactions frequently involve specific cellular tropism. Accurate
      characterization of cells involved in these initial interactions is complicated
      by the response to the microbe. We describe a method utilizing RNAlater for
      Fluorescence Activated Cell Sorting of these critical cells that minimizes the
      downstream perturbation in the gene expression profile.

PMID- 17512622
TI  - Engineering antibodies for clinical applications.
AB  - Molecular engineering has contributed immensely to the clinical success of
      antibodies in recent years. The modular structure of antibodies has permitted
      their modification in numerous ways, to meet various clinical requirements. With
      the help of antibody engineering, it has been possible to modify the molecular
      size, pharmacokinetics, immunogenicity, binding affinity, specificity and
      effector function of antibodies. In addition, fusion proteins of antibodies with
      various proteins and peptides have yielded targeted biological modifiers, toxins
      and imaging agents. This review focuses on the recent trends in antibody
      engineering for improving their clinical utility.

PMID- 17512623
TI  - Hypoxia induced expression of endogenous markers in vitro is highly influenced by
      pH.
AB  - BACKGROUND: Genes such as carbonic anhydrase IX (Ca9), glucose transporter 1
      (Glut1), lactate dehydrogenase A (LDH-A), osteopontin (OPN) and lysyl oxidase
      (LOX) have been suggested as hypoxic markers, but inconsistent results suggest
      that factors other than oxygen influence their expression. The current study is a
      detailed investigation using a range of pH values from 6.3 to 7.5 in two human
      cell lines to establish the pH dependency of hypoxia induced gene expression.
      METHODS: Human tumour cell lines (uterine cervix squamous cell carcinoma (SiHa)
      and pharyngeal squamous cell carcinoma [FaDu(DD)]) were used. Hypoxia was induced
      by gassing cells in airtight chambers with various oxygen concentrations (21%,
      1%, 0.1%, 0.01% and 0%) for up to 24h. The media were titrated to a range of pH
      values (7.5, 7.0, 6.7, 6.5 and 6.3). Gene expression was determined by real-time
      PCR. RESULTS: In both SiHa and FaDu(DD) cells Ca9 and LOX reached the highest
      level of expression at 1% oxygen. In FaDu(DD) cells, a pH of 6.5 had a medium
      suppression effect on the hypoxia induced expression of Ca9. pH 6.3 resulted in
      severe suppression of expression for Ca9 and LOX in both SiHa and FaDu(DD). Glut1
      and LDH-A had a similar expression pattern to each other, with a maximum
      expression at 0.01% oxygen, in both cell lines. For these genes pH 6.5 and 6.3
      changed the expression pattern in SiHa cells. OPN was up regulated at low oxygen
      in SiHa cells, but was not induced by hypoxia in FaDu(DD) cells. CONCLUSION: As
      tumour hypoxia occurs in a deprived microenvironment, other environmental
      factors, for example low pH, might interact with the effect of low oxygen
      concentration on gene expression. This study shows that pH in two cell lines has
      a profound influence on the oxygen dependent induction of certain endogenous
      hypoxic markers.

PMID- 17512624
TI  - Multicenter validation study of two blockcycler- and one capillary-based real
      time PCR methods for the detection of Salmonella in milk powder.
AB  - A collaborative study including 13 German laboratories was conducted to evaluate
      the performance of two non-patented real-time PCR methods for the detection of
      Salmonella in milk powder targeting the ttrC/ttrA- or the invA gene. The
      enrichment procedure and sample DNA preparation method prior to the real-time PCR
      was the same for both systems and the identical DNA extraction samples were
      analysed. The traditional cultural method according to EN ISO 6579:2002 for the
      detection of Salmonella in food was performed in each laboratory as the
      reference. The participants received twelve coded milk powder samples each of 25
      g for the analysis. Four of them were Salmonella negative (level L0), four
      artificially contaminated with <3 MPN/g Salmonella Typhimurium (level L1) and
      four artificially contaminated with 3.6 MPN/g S. Typhimurium (level L2) to the
      beginning of the experiment. Of the 13 laboratories 12 used various models of
      real-time PCR blockcyclers conducting both real-time PCR assays and three
      laboratories the Light Cycler 2.0 system (Roche Bioscience) conducting the ttr
      based real-time PCR assay only. The relative accuracy for both real-time PCR
      assays performed on blockcyclers was for level L0 97.5%. For level L1 the
      relative accuracy was 94.1% and for level L2 it was 100% for both assays. The
      relative accuracy on the Light Cycler 2.0 system was 100% for all levels applied
      to the ttr-real-time PCR.

PMID- 17512625
TI  - Yeast dynamics during spontaneous wine fermentation of the Catalanesca grape.
AB  - Although the use of starter cultures in winemaking has improved the
      reproducibility and predictability of wine quality, the main drawback to this
      practice is the lack of the typical traits of wines produced by spontaneous
      fermentation. In this study, we identified for the first time the yeast
      population occurring during spontaneous fermentation of the Catalanesca white
      grape, a variety from Campania (Italy). Yeasts were identified using molecular
      tools: PCR-DGGE and partial sequence analysis of the 26S rRNA gene from isolates.
      Eighteen different species belonging to 11 different genera were identified.
      Hanseniaspora spp., Issatchenkia spp. and Candida spp. were the dominant yeasts
      during the early stages of fermentation, while the middle and end phases were
      dominated by Saccharomyces cerevisiae. Four species of Issatchenkia spp., rarely
      isolated from wine fermentation, were found in this study accounting for the
      33.5% of the total isolates. The RAPD-PCR screening of the isolates followed by
      partial rRNA gene sequencing proved to be a very effective approach to first
      differentiate the isolates and then identify yeast species involved in a wine
      making procedure. The results show very high yeast diversity in this natural wine
      fermentation and also highlight the possibility of considering interesting
      autochthonous strains for starter selection.

PMID- 17512626
TI  - Highly efficient cationic hydroxyethylated cholesterol-based nanoparticle
      mediated gene transfer in vivo and in vitro in prostate carcinoma PC-3 cells.
AB  - Optimal gene therapy for tumors must deliver DNA to tumor cells with high
      efficiency and minimal toxicity. It has been reported that in non-viral gene
      delivery, the hydroxyethyl group at the amino terminal in cationic lipid was
      important for high transfection efficiency. Therefore, in this study, we
      developed new cationic nanoparticles (NP-OH) composed of cholesteryl-3beta
      carboxyamidoethylene-N-hydroxyethylamine and Tween 80, and optimized in vitro and
      in vivo transfections for potential use as a non-viral DNA vector into human
      prostate tumor PC-3 cells and xenografts. In vitro transfection resulted in
      efficient DNA transfer when positive-charged nanoplex was prepared in the
      presence of sodium chloride (NaCl). In in vivo transfection, negative-charged
      nanoplex formed in water strongly induced the gene expression compared with
      positive-charged nanoplex when directly transfected into xenografts. These
      transfection efficiencies in vitro and in vivo were comparable to each commercial
      product. Furthermore, NP-OH nanoplexes displayed no induction of tumor necrosis
      factor (TNF)-alpha when administered by intravenous injection. The results of the
      experiments provided optimal conditions to form NP-OH nanoplex for gene delivery
      in vitro and in vivo. NP-OH is a potential non-viral DNA vector for the local
      treatment of tumor and in vitro.

PMID- 17512627
TI  - A Toll-like receptor 7 single nucleotide polymorphism protects from advanced
      inflammation and fibrosis in male patients with chronic HCV-infection.
AB  - BACKGROUND/AIMS: HCV-infection leads to development of liver fibrosis, causing
      morbidity and mortality. Multiple factors influence the progression of fibrosis,
      including genetic factors. Since HCV is an RNA virus, a role for TLR7 in the
      immune response against HCV is likely. No systematic analysis of TLR7 single
      nucleotide polymorphisms (SNPs) has been published. METHODS: We sequenced TLR7 in
      52 women and investigated SNPs with an allele frequency >5% in 807 patients with
      chronic HCV-infection by melting curve analysis. We analyzed the effect of TLR7
      SNPs on grade of inflammation and stage of fibrosis as determined by liver
      biopsy. RESULTS: We detected five TLR7 SNPs, three of which showed a frequency
      >5%. One variant, c.1-120T>G, was more common in patients with no or little
      inflammation than in patients with grades 2-4 (10.7% vs. 6.1%; P=0.034). The
      variant was also enriched in patients with no or little fibrosis compared to
      those with higher stages (12.6% vs. 6.6%; P=0.005). The difference was fully
      attributable to male patients. CONCLUSIONS: This is the first analysis of TLR7
      SNPs in patients with chronic HCV-infection. Our data suggest that the c.1-120G
      TLR7 allele offers protection from the development of inflammation and fibrosis
      in male patients with chronic HCV-infection.

PMID- 17512628
TI  - Outcome of hepatitis C infection: bleak or benign?

PMID- 17512629
TI  - Gene essentiality, gene duplicability and protein connectivity in human and
      mouse.
AB  - It has previously been found that, in yeast, gene essentiality is positively
      correlated with protein connectivity (number of interaction partners) but
      negatively correlated with the existence of gene duplicates and that highly
      connected proteins tend to have a low gene duplicability. Using data from human
      and mouse, we show here that, in mammals, the first of these relationships holds
      true, but unlike the second relationship in yeast, highly connected mammalian
      proteins tend to have a high gene duplicability, and there is no correlation
      between gene essentiality and gene duplication in mammals.

PMID- 17512631
TI  - Nonmelanoma skin cancer.

PMID- 17512632
TI  - MRSA control and the counter-culture.

PMID- 17512630
TI  - Matrices and scaffolds for DNA delivery in tissue engineering.
AB  - Regenerative medicine aims to create functional tissue replacements, typically
      through creating a controlled environment that promotes and directs the
      differentiation of stem or progenitor cells, either endogenous or transplanted.
      Scaffolds serve a central role in many strategies by providing the means to
      control the local environment. Gene delivery from the scaffold represents a
      versatile approach to manipulating the local environment for directing cell
      function. Research at the interface of biomaterials, gene therapy, and drug
      delivery has identified several design parameters for the vector and the
      biomaterial scaffold that must be satisfied. Progress has been made towards
      achieving gene delivery within a tissue engineering scaffold, though the design
      principles for the materials and vectors that produce efficient delivery require
      further development. Nevertheless, these advances in obtaining transgene
      expression with the scaffold have created opportunities to develop greater
      control of either delivery or expression and to identify the best practices for
      promoting tissue formation. Strategies to achieve controlled, localized
      expression within the tissue engineering scaffold will have broad application to
      the regeneration of many tissues, with great promise for clinical therapies.

PMID- 17512633
TI  - An increased incidence of Enterobacter cloacae in a cardiovascular ward.
AB  - Routine surveillance in a cardiovascular ward showed that the incidence of
      Enterobacter cloacae isolated from sputum and oropharyngeal cultures in June 2004
      increased to 27.6% (8/29) compared to 5.5% (12/219) from the rest of the hospital
      during the same period (OR=13.2; 95% CI 2.97-58.7; P<0.05). While an increase in
      E. cloacae pneumonia was not verified, an investigation was undertaken by the
      infection control team to prevent an outbreak. The estimate of relative risk for
      E. cloacae infection was based on a case-control study which measured exposure to
      intubation, history of a stay in the intensive care unit (ICU) and oral care
      between patients with E. cloacae and those negative for E. cloacae. An odds ratio
      of 13.2 suggested cross-contamination via the transoesophageal echocardiography
      (TOE) probe in the ICU prior to transfer to the cardiovascular ward. Pulsed-field
      gel electrophoresis and antibiogram patterns were also consistent with this
      hypothesis. Intervention was undertaken in the form of enforcing the disinfection
      of TOE probes using a 0.55% phtharal solution and the use of a single-use sheath
      to protect the probe from recontamination. Following intervention, the incidence
      rate returned to previous levels. This report illustrates the limitations in the
      effectiveness of current nosocomial surveillance strategies due to the
      retrospective nature of analysis. Improved surveillance methods such as data
      mining tools specifically applicable to the institution, patient population,
      region and country are needed to increase the sensitivity of detecting
      unrecognized outbreaks, including cross-contamination.

PMID- 17512634
TI  - Preparations and limitations for prevention of severe acute respiratory syndrome
      in a tertiary care centre of India.
AB  - This short-term observational study of infection control practice was performed
      in the medical emergency outpatient department (EMOPD) of a tertiary-care
      hospital in India when threatened by an outbreak of severe acute respiratory
      syndrome (SARS). An investigator attended the lobby daily to screen patients with
      symptoms for SARS. Patient/attendant load, patient flow, medical staff working
      practices and position in the EMOPD were observed. Infection control measures
      such as fumigation and cleaning were noted, as was the EMOPD laboratory function,
      use of personnel protection and display of information on infectious diseases. A
      total of 162 (7.4%) of the 2165 patients surveyed had respiratory symptoms but no
      cases of SARS were found. The flow of patients and their attendants was not
      systematic. No laboratory tests for SARS were available, and no educational
      material on SARS was displayed. The EMOPDs in key hospitals need be able to
      screen for infectious diseases, especially in view of the threats from SARS and
      Avian influenza.

PMID- 17512635
TI  - Comparison of the National Surgical Site Infection surveillance data between The
      Netherlands and Germany: PREZIES versus KISS.
AB  - As there has been increasing interest in comparing surgical site infection (SSI)
      rates between countries, we compared the SSI surveillance data for The
      Netherlands ('PREZIES') and Germany ('KISS'). Both surveillance systems have
      comparable protocols with many similar risk factors, including SSI definitions
      developed by the Centers for Disease Control and Prevention and optional
      postdischarge surveillance. Nine surgical procedure categories from several
      specialities were included, the reporting of which were similar, with respect to
      content and with enough data for proper comparison. Differences for the SSI data
      were found between PREZIES and KISS for duration of surgery, wound contamination
      class, American Society of Anesthesiologists physical status classification and
      the postoperative duration of hospitalization. A significantly higher superficial
      SSI rate was found for seven surgical procedures according to PREZIES and a
      higher deep SSI rate for five procedures. When considering only deep SSI during
      hospitalization, the differences in SSI rates were much smaller. Differences in
      intensity of postdischarge surveillance led to 34% of SSI being detected after
      discharge for PREZIES and 21% for KISS. In conclusion, even though similar
      infection surveillance protocols are used in The Netherlands and Germany,
      differences occurred in the implementation. Comparisons between countries are
      most reliable if only deep SSIs during hospitalization are taken into account,
      since these SSI are not affected by postdischarge surveillance and the diagnostic
      sensitivity for deep SSI is probably more alike between countries than for
      superficial SSI.

PMID- 17512636
TI  - Carriage of meticillin-resistant Staphylococcus aureus among patients admitted
      with fractured neck of femur.

PMID- 17512637
TI  - RAPD for the typing of Staphylococcus aureus implicated in nosocomial infection.

PMID- 17512638
TI  - Evidence-based emergency medicine review. Prevention of contrast-induced
      nephropathy in the emergency department.
AB  - STUDY OBJECTIVE: Contrast-induced nephropathy is the third leading cause of
      hospital-acquired acute renal failure. Expanded use of contrast-enhanced imaging
      exposes an ever-widening number of patients to this renal toxin. We perform an
      evidence-based emergency medicine review comparing different therapies to prevent
      contrast-induced nephropathy. We limit our review to prophylactic therapies that
      are practical for an emergency department setting. METHODS: We searched MEDLINE,
      EMBASE, and the Cochrane Library for randomized trials comparing a wide range of
      medications to prevent contrast-induced nephropathy. We defined contrast-induced
      nephropathy by a commonly used surrogate measure of renal failure: a 25% or 0.5
      mg/dL absolute increase in serum creatinine level from baseline 48 to 72 hours
      postcontrast. We limited our review to only trials for patients with baseline
      renal insufficiency, who are most at risk for contrast-induced nephropathy. We
      excluded prophylactic protocols requiring more than 2 hours precontrast to
      initiate and any trials of experimental medications or those that required
      invasive monitoring. We used standard criteria to appraise the quality of
      published trials. RESULTS: We found 7 randomized trials; 3 using N
      acetylcysteine, 2 using theophylline, and 1 each using bicarbonate and ascorbic
      acid. Although many of these trials showed statistically significant reductions
      in the risk for contrast-induced nephropathy, none were sufficiently powered to
      detect reductions in mortality rate or the need for dialytic therapy. CONCLUSION:
      Evidence from randomized trials shows that these interventions (theophylline,
      bicarbonate, and ascorbic acid) under review were appropriate to an ED setting
      and decreased the risk of contrast-induced nephropathy. The case for the
      effectiveness (N-acetylcysteine) was less certain.

PMID- 17512640
TI  - Understanding the persona of clinical instructors: the use of students' doodles
      in nursing research.
AB  - BACKGROUND: While it is true that understanding the attributes and unique
      distinction of the nursing faculty has been the subject of most of the studies,
      little is known about how the use of doodles can help surface the persona of the
      clinical instructors. OBJECTIVE: This study aims to capture the essence or the
      lebenswelt of the concept of "clinical instructor" from the lens of students'
      doodles which have been considered as a powerful qualitative tool in articulating
      individual experiences. METHOD: A total of 195 senior nursing students recruited
      from a comprehensive university in the Philippines were the subjects in this
      qualitative study. Data were gathered from self-generated illustrations and
      written explanations made by the subjects to identify their concept of effective
      and ineffective clinical instructors. Phenomenological reduction was observed
      through a repertory grid, where doodles drawn were listed, categorized and
      thematised to reveal the qualities of the clinical instructor. CONCLUSIONS: The
      subjective nature of the findings, though not generalizable, has surfaced how
      doodling can be a potent tool in identifying collective interpretation of the
      essence of health professions construct such as the one under study. The doodles
      revealed that an effective clinical instructor (enlightening, engaging and
      embracing) is one who is able to facilitate the learning of the students as well
      as being able to establish a harmonious learning atmosphere for and with the
      students. On the other hand, an ineffective clinical instructor (detrimental,
      dangling, and disturbing) impedes students' development in the clinical practice
      by causing conflict through their personal attitudes and their teaching
      strategies. This can have benefits for clinical instructors, to improve
      themselves and realize the impact of their attributes to the clinical learning of
      students.

PMID- 17512639
TI  - Microarray analyses of pituitary adenylate cyclase activating polypeptide (PACAP)
      regulated gene targets in sympathetic neurons.
AB  - The high and preferential expression of the PAC(1)(short)HOP1 receptor in
      postganglionic sympathetic neurons facilitates microarray studies for mechanisms
      underlying PACAP-mediate neurotrophic signaling in a physiological context.
      Replicate primary sympathetic neuronal cultures were treated with 100 nM PACAP27
      either acutely (9 h) or chronically (96 h) before RNA extraction and preparation
      for Affymetrix microarray analysis. Compared to untreated control cultures, acute
      PACAP treatment modulated significantly the expression of 147 transcripts of
      diverse functional groups, including peptides, growth factors/cytokines,
      transcriptional factors, receptors/signaling effectors and cell cycle regulators,
      that collectively appeared to facilitate neuronal plasticity, differentiation
      and/or regeneration processes. Some regulated transcripts, for example, were
      related to BDNF/TrkB, IL-6/Jak2/Socs2 and TGF/follistatin signaling; many
      transcripts affected bioactive peptide and polyamine biosynthesis. Although
      chronic PACAP treatments altered the expression of 109 sympathetic transcripts,
      only 43 transcripts were shared between the acute and chronic treatment data
      sets. The PACAP-mediated changes in transcript expression were corroborated
      independently by quantitative PCR measurement. The PACAP-regulated transcripts in
      sympathetic neurons did not bear strong resemblance to those in PACAP-treated
      pheochromocytoma cells. However, many PACAP-targeted sympathetic transcripts,
      especially those related to peptide plasticity and nerve regeneration processes,
      coincided significantly with genes altered after peripheral nerve injury. The
      ability for sympathetic PAC(1)(short)HOP1 receptors to engage multiple downstream
      signaling cascades appeared to be reflected in the number and diversity of genes
      targeted in a multifaceted strategy for comprehensive neurotrophic responses.

PMID- 17512641
TI  - Reliability of physical activity measures from accelerometry among preschoolers
      in free-living conditions.
AB  - BACKGROUND & AIMS: Physical activity (PA) is a major determinant of obesity.
      Accelerometers have been reported to provide valid measures among adults.
      However, studies among preschoolers rarely report positive findings. To assess
      the day-to-day variability of accelerometers in preschoolers. METHODS: Uni-axial
      accelerometer (Actigraph monitor AM 7164-2.2) counts including one weekend from
      the time of getting up in the morning until bedtime. RESULTS: On average, boys
      showed 899 counts per minute (cpm) compared to 764 for girls (p<0.01; overall
      mean 828 cpm). Intra-individual correlation for accelerometry data between single
      days of examination was low with Pearson correlation coefficients between r=0.31
      and 0.51. Furthermore, child's body mass index (BMI) and accelerometer measures
      were not related to each other (Pearson's correlation coefficient r=-0.06).
      Subsequent analyses showed higher measures (+50%cpm; p<0.01) for instruments
      placed in front of the umbilicus compared to instruments placed at the right hip.
      CONCLUSIONS: Measurements of uni-axial accelerometers showed a low reliability
      among preschoolers. Uni-axial accelerometers placed on elastic belts might
      measure PA with low precision among preschoolers under free-living conditions
      possibly due to slipping instruments. This might explain lacking findings of an
      association between PA and obesity in studies among preschoolers.

PMID- 17512642
TI  - Influenza vaccination in healthcare workers: a survey of coverage in French
      cystic fibrosis treatment centres.

PMID- 17512643
TI  - Changing patterns of radionuclide distribution in Irish Sea subtidal sediments.
AB  - This paper presents new data on the distribution of long-lived radionuclides in
      Irish Sea subtidal sediments, contaminated as a result of the BNFL Sellafield
      discharges. The results from different sampling campaigns in 1999 have been
      combined to assess the extent of radionuclide mobility relative to earlier
      surveys, in both the eastern and western Irish Sea areas, and to investigate
      changes in radionuclide distribution over time. The results appear to confirm the
      trend of continuing re-distribution and transfer of contamination away from the
      English coast. West of the Isle of Man, radionuclide concentrations and
      inventories have remained more or less constant. The inventory of radionuclides
      in sandy sediments in the eastern Irish Sea is still under-represented by current
      sampling, but could be improved by deeper and more extensive vibrocoring.

PMID- 17512644
TI  - Modification of retraction technique for better visibility during mandibular
      sagittal split ramus osteotomy.

PMID- 17512645
TI  - Women's lived experience of fear of childbirth.
AB  - OBJECTIVE: to describe women's lived experience of fear of childbirth. DESIGN: a
      qualitative study using a phenomenological approach and a lifeworld perspective.
      Data were collected via tape-recorded interviews. SETTING: Sahlgrenska University
      Hospital, Goteborg, Sweden in 2003. PARTICIPANTS: eight pregnant women (24-37
      gestational weeks) seeking help within an outpatient clinic for women with severe
      fear of childbirth. Two of the women were primiparous. FINDINGS: four
      constituents were identified: feeling of danger that threatens and appeals;
      feeling trapped; feeling like an inferior mother-to-be and on your own. The
      essential structure was described as 'to lose oneself as a woman into
      loneliness'. KEY CONCLUSIONS: fear of childbirth affects women in such a way that
      they start to doubt themselves and feel uncertain of their ability to bear and
      give birth to a child. Previous birth experience was central to the multiparous
      women. They described their experiences of suffering in relation to the care they
      received during childbirth. This mainly concerned pain and negative experiences
      with staff. IMPLICATIONS FOR PRACTICE: pregnant women who fear childbirth are an
      exposed group in need of much support during pregnancy and childbirth. The
      encounter between the woman and the midwife can be a way of breaking down the
      feeling of loneliness and restoring the woman's trust in herself as a
      childbearing woman.

PMID- 17512646
TI  - Changes in muscle group work associated with changes in gait speed of persons
      with stroke.
AB  - BACKGROUND: Knowledge of associations between changes in muscle work with changes
      in gait speed could assist gait training in persons with stroke. The purpose of
      the study was to determine changes in the work of major muscle groups during gait
      that were associated with increases in walking speed of persons with stroke
      following training. METHODS: The gait of 28 subjects (14 males, 14 females) with
      mean age of 64.2 (SD 11.7) years, at 4.8 (SD 6.9) years post stroke was studied
      using two-dimensional motion analysis before and after a strength training
      program. Outcome variables were changes in gait speed and changes in work
      associated with the hip flexors and extensors, knee flexors and extensors and
      ankle plantar flexors bilaterally. A stepwise linear regression analysis
      determined best positive work predictors of changes in gait speed. FINDINGS: Hip
      extension work in early stance and ankle plantarflexion work in late stance of
      the affected side accounted for 74.9% of the variance in change of gait speed; a
      second model showed that hip extension work in early stance of the affected and
      less-affected sides accounted for 74.3%, a similar amount of variance.
      INTERPRETATION: This work is the first to explore the changes in muscle work
      during gait that are associated with speed increases in persons with stroke.
      Augmenting hip extensor work in early stance on both sides, as well as ankle
      plantarflexion thrust on the affected side may be particularly beneficial in
      increasing the speed of walking of persons with stroke.

PMID- 17512647
TI  - Thigh-calf contact force measurements in deep knee flexion.
AB  - BACKGROUND: Knee models often do not contain thigh-calf contact which occurs in
      deep knee flexion. Thigh-calf contact is expected to reduce muscle forces and
      thereby affects internal stresses in the knee joint. The purpose of this study
      was to measure thigh-calf contact forces. Two deep knee flexion activities were
      selected: squatting and kneeling. METHODS: Ten healthy subjects participated in
      the experiment. Contact pressures between the thigh and calf were measured using
      the Tekscan Conformat pressure mapping sensor. Knee flexion angles were measured
      unilaterally using an infrared motion capture system. Contact forces were
      averaged in terms of means and standard deviations. The magnitude and location of
      the resultant contact force were calculated. Correlations between anthropometric
      subject parameters and experimental outcome were studied. FINDINGS: In general,
      thigh-calf contact did not take place below 130 degrees knee flexion. The average
      maximal contact forces for each leg were 34.2% bodyweight during squatting and
      30.9% bodyweight during kneeling. Corresponding average maximal knee flexion
      angles were 151.8 degrees during squatting and 156.4 degrees during kneeling.
      Thigh and calf circumferences were correlated with the contact force
      measurements. INTERPRETATION: The current study shows that thigh-calf contact is
      substantial (>30% bodyweight on one leg) and likely reduces the forces inside the
      knee during deep knee flexion. Subsequently, total knee replacements may be
      subjected to lower loads than assumed before, which reduces the risk of implant
      failure at large flexion angles. Results presented in this study can be utilized
      in knee models that focus on deep knee flexion.

PMID- 17512648
TI  - Side difference in the hip and knee joint moments during sit-to-stand and stand
      to-sit tasks in individuals with hemiparesis.
AB  - BACKGROUND: No study has reported the differences between sides in the net
      muscular moment of lower limbs of subjects with hemiparesis during sit-to-stand
      and stand-to-sit tasks in various foot positions. Moreover, the asymmetry of
      lower-joint moments has not yet been related to muscular weakness of the lower
      limbs in this population. METHODS: A convenience sample of 12 individuals (mean
      age (standard deviation): 49.7 (9.0) years) with chronic hemiparesis due to
      stroke were asked to stand up and sit down at their natural speed in four foot
      positions. The joint moments at the hip and knee on both sides during the tasks
      were estimated with an inverse dynamic approach while the dynamic concentric
      strength in extension at the hip and knee was assessed with a Biodex dynamometric
      system. Statistical analyses (paired t-tests and ANOVAs) were used to assess the
      effects of sides and foot position factor on the asymmetry in the hip and knee
      joint moments. The level of association between muscle weakness and the asymmetry
      in the joint moments was quantified with Pearson correlation coefficients (r).
      FINDINGS: At the knee, the extensor moments were significantly lower on the
      affected side (P<0.05) and were affected by the foot position. At the hip, the
      moments were not significantly different between sides and were slightly modified
      by the foot positions. There were also strong correlations (0.70<r<0.89; P<0.05,
      for symmetrical foot position) between the asymmetry in knee extensor moments and
      the asymmetry in strength. No relation was established at the hip.
      INTERPRETATION: The sit-to-stand and stand-to-sit tasks are characterized by a
      marked asymmetry in the knee extensor moments, which is associated with knee
      extensor weakness.

PMID- 17512649
TI  - Peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) are a biologically diverse and uncommon group
      of diseases. Compared to their B-cell counterparts, PTCLs remain largely
      unexplored and the optimal treatment ill-defined due to disease rarity and
      biological heterogeneity. With the notable exception of ALK-pos anaplastic large
      cell lymphoma (ALCL), the prognosis of most PTCL subtypes is extremely is poor
      with a 5 y overall survival of approximately 15-30% in most series. The
      international prognostic index has been useful in defining different risk groups
      within some PTCL subtypes, including PTCL unspecified (PTCLU). Attempts have been
      made to define disease subgroups within the biologically heterogeneous PTCLU
      based on T-helper chemokine receptor profile and/or gene expression profiling
      which may aid in tailoring new therapies. Future clinical trials are needed that
      focus specifically on PTCL to advance our understanding and define the optimal
      management in this disease.

PMID- 17512650
TI  - Strengths and limitations of using repeat-dose toxicity studies to predict
      effects on fertility.
AB  - The upcoming European chemicals legislation REACH (Registration, Evaluation, and
      Authorisation of Chemicals) will require the risk assessment of many thousands of
      chemicals. It is therefore necessary to develop intelligent testing strategies to
      ensure that chemicals of concern are identified whilst minimising the testing of
      chemicals using animals. Xenobiotics may perturb the reproductive cycle, and for
      this reason several reproductive studies are recommended under REACH. One of the
      endpoints assessed in this battery of tests is mating performance and fertility.
      Animal tests that address this endpoint use a relatively large number of animals
      and are also costly in terms of resource, time, and money. If it can be shown
      that data from non-reproductive studies such as in-vitro or repeat-dose toxicity
      tests are capable of generating reliable alerts for effects on fertility then
      some animal testing may be avoided. Available rat sub-chronic and fertility data
      for 44 chemicals that have been classified by the European Union as toxic to
      fertility were therefore analysed for concordance of effects. Because it was
      considered appropriate to read across data for some chemicals these data sets
      were considered relevant for 73 of the 102 chemicals currently classified as
      toxic to reproduction (fertility) under this system. For all but 5 of these
      chemicals it was considered that a well-performed sub-chronic toxicity study
      would have detected pathology in the male, and in some cases, the female
      reproductive tract. Three showed evidence of direct interaction with oestrogen or
      androgen receptors (linuron, nonylphenol, and fenarimol). The remaining chemicals
      (quinomethionate and azafenidin) act by modes of action that do not require
      direct interaction with steroid receptors. However, both these materials caused
      in-utero deaths in pre-natal developmental toxicity studies, and the relatively
      low NOAELs and the nature of the hazard identified in the sub-chronic tests
      provides an alert for possible effects on fertility (or early embryonic
      development), the biological significance of which can be ascertained in a
      littering (e.g. 2-generation) study. From the chemicals reviewed it would appear
      that where there are no alerts from a repeat-dose toxicity study, a pre-natal
      developmental toxicity study and sex steroid receptor binding assays, there
      exists a low priority for animal studies to address the fertility endpoint. The
      ability for these types of tests to provide alerts for effects on fertility is
      clearly dependent on the mode of action of the toxicant in question. Further work
      should therefore be performed to determine the 'failure rate' of this type of
      approach when applied to a larger group of chemicals with diverse modes of
      action.

PMID- 17512651
TI  - Garlic oil ameliorates ferric nitrilotriacetate (Fe-NTA)-induced damage and tumor
      promotion: implications for cancer prevention.
AB  - Intraperitoneal injection of ferric nitrilotriacetate (Fe-NTA) to rats and mice
      results in iron-induced free radical injury and cancer in kidneys. This study was
      designed to investigate the effects of garlic oil on Fe-NTA-induced damage and
      tumor promotion. Pretreatment of rats with garlic oil at a dose regimen of 50-100
      mg/kg body weight for a week significantly and dose dependently protected against
      Fe-NTA induced damage as well as tumor promotion. Garlic oil afforded protection
      against hepatic lipid peroxidation, generation of hydrogen peroxide, preserved
      glutathione levels and activities of antioxidant enzymes. A protection against Fe
      NTA induced hepatic tumor promotion was also apparent as inhibition in the
      modulation of hepatic tumor markers viz., ornithine decarboxylase activity and
      DNA synthesis. These results clearly demonstrate the role of oxidative stress and
      its relation to tumor promotion and suggest protective effects of garlic oil
      against Fe-NTA induced hepatic toxicity and it can serve as potent
      chemopreventive agent to suppress oxidant-induced tissue injury and
      carcinogenesis.

PMID- 17512652
TI  - Anthocyanins inhibit airway inflammation and hyperresponsiveness in a murine
      asthma model.
AB  - Asthma is a common chronic inflammatory disease regulated by coordination of T
      helper cell type 2 (Th2) cytokines and inflammatory signal molecules.
      Additionally, oxidative stress may play an important role in airway inflammation
      such as eosinophilia, mucus hypersecretion, and airway hyperresponsiveness (AHR).
      In the present report, we investigated whether anthocyanins would reduce airway
      inflammation in a mouse asthma model immunized and challenged with ovalbumin
      (OVA). OVA inhalation elicited inflammatory responses characterized by
      eosinophilia and increased lipid hydroperoxide (LPO) in bronchoalveolar lavage
      (BAL) fluid, enhanced pause (Penh), increased glycoprotein and proliferating cell
      nuclear antigen (PCNA) expressions in mucus hypersecretion, and an increased
      expression of various cytokines and cyclooxygenase (COX) 2 in lung tissues. All
      parameters were attenuated in a dose-dependant manner by the administration of
      anthocyanins. These results suggest that anthocyanins may attenuate the
      development of asthma by downregulating Th2 cytokines, proinflammatory cytokines,
      and COX-2. Our findings suggest that anthocyanins have positive contributions as
      a dietary supplement for the prevention of asthma.

PMID- 17512653
TI  - Relation between structural and release properties in a polysaccharide gel
      system.
AB  - The potential utility of kappa-carrageenan gels for preparing drug release
      devices is here shown. Structural properties of kappa-carrageenan gels prepared
      with different salt composition and containing Ketoprofen sodium salt, as model
      drug, have been evaluated with static light scattering and rheological
      measurements. These properties have been correlated with release profiles in
      vitro at pH 5.5. Release properties from gelled matrices have been compared with
      those obtained by two commercial products containing the same drug. Results show
      that: i) in this system it is possible to easily control the gel texture by using
      different cationic concentration; ii) the kinetics of drug release by kappa
      carrageenan gels are dependent on the structural properties of matrices; iii) in
      the typical interval time used in classical local applications, all gel samples
      release the loaded drug almost completely, at difference with the commercial
      products. All these findings can provide useful suggestions for the realization
      of classical topical release systems.

PMID- 17512654
TI  - Collision induced spatial organization of microtubules.
AB  - The dynamic behavior of microtubules in solution can be strongly modified by
      interactions with walls or other structures. We examine here a microtubule growth
      model where the increase in size of the plus-end is perturbed by collisions with
      other microtubules. We show that such a simple mechanism of constrained growth
      can induce ordered structures and patterns from an initially isotropic and
      homogeneous suspension. We find that microtubules self-organize locally in
      randomly oriented domains that grow and compete with each other. A weak
      orientation bias, similar to the one induced by gravity or cellular boundaries is
      enough to influence the domain growth direction, eventually leading to a
      macroscopic sample orientation.

PMID- 17512655
TI  - Freehand 3D ultrasound reconstruction algorithms--a review.
AB  - Three-dimensional (3D) ultrasound (US) is increasingly being introduced in the
      clinic, both for diagnostics and image guidance. Although dedicated 3D US probes
      exist, 3D US can also be acquired with the still frequently used two-dimensional
      (2D) US probes. Obtaining 3D volumes with 2D US probes is a two-step process.
      First, a positioning sensor must be attached to the probe; second, a
      reconstruction of a 3D volume can be performed into a regular voxel grid. Various
      algorithms have been used for performing 3D reconstruction based on 2D images. Up
      till now, a complete overview of the algorithms, the way they work and their
      benefits and drawbacks due to various applications has been missing. The lack of
      an overview is made clear by confusions about algorithm and group names in the
      existing literature. This article is a review aimed at explaining and
      categorizing the various algorithms into groups, according to algorithm
      implementation. The algorithms are compared based on published data and our own
      laboratory results. Positive and practical uses of the various algorithms for
      different applications are discussed, with a focus on image guidance.

PMID- 17512656
TI  - Complex adaptation and system structure.
AB  - The structural organization of biological systems is one of nature's most
      fascinating aspects, but its origin and functional role is not yet fully
      understood. For instance, basic adaptational mechanisms like genetic mutation and
      Hebbian adaptation seem to be generic and invariant across many species and are,
      on their own, fairly well investigated and understood. However, it is the
      organism's structure - the representations these mechanisms act upon - that bears
      the complex functional effects of these mechanisms. While typical technical
      approaches to system design require detailed problem models and suffer from the
      need to explicitly take care of all possible cases, the organization of
      biological systems seems to induce inherent adaptability, flexibility and
      robustness. In this discussion paper we address the concept of structured
      variability, particularly the role of system structure as implementing a certain
      representation on which basic variational mechanisms act on. The functional
      adaptability (or search distribution) depends crucially on this representation.

PMID- 17512657
TI  - Biodegradation of aged polycyclic aromatic hydrocarbons (PAHs) by microbial
      consortia in soil and slurry phases.
AB  - Microbial consortia isolated from aged oil-contaminated soil were used to degrade
      16 polycyclic aromatic hydrocarbons (15.72 mgkg(-1)) in soil and slurry phases.
      The three microbial consortia (bacteria, fungi and bacteria-fungi complex) could
      degrade polycyclic aromatic hydrocarbons (PAHs), and the highest PAH removals
      were found in soil and slurry inoculated with fungi (50.1% and 55.4%,
      respectively). PAHs biodegradation in slurry was lower than in soil for bacteria
      and bacteria-fungi complex inoculation treatments. Degradation of three- to five
      ring PAHs treated by consortia was observed in soil and slurry, and the highest
      degradation of individual PAHs (anthracene, fluoranthene, and benz(a)anthracene)
      appeared in soil (45.9-75.5%, 62-83.7% and 64.5-84.5%, respectively) and slurry
      (46.0-75.8%, 50.2-86.1% and 54.3-85.7%, respectively). Therefore, inoculation of
      microbial consortia (bacteria, fungi and bacteria-fungi complex) isolated from in
      situ contaminated soil to degrade PAHs could be considered as a successful
      method.

PMID- 17512658
TI  - Comments on "Biosorption of nickel from protonated rice bran".
AB  - This letter explains the appropriate way to calculate the parameters in pseudo
      first and second order kinetics, Langmuir and Freundlich isotherm.

PMID- 17512659
TI  - Study of the degradation behaviour of dimethoate under microwave irradiation.
AB  - In this work, the degradation of dimethoate under microwave irradiation assisted
      advanced oxidation processes (MW/oxidants) were studied. The efficiencies of the
      degradation of dimethoate in dilute aqueous solutions for a variety of oxidants
      with or without MW irradiation were compared. The results showed that the
      synergistic effects between MW and K(2)S(2)O(8) had high degradation efficiency
      for dimethoate. Simultaneously, UV/TiO(2)/K(2)S(2)O(8) photocatalytic oxidation
      degradation of dimethoate was investigated. The experimental results indicated
      that the method of microwave degradation of organic pollutants in the presence of
      oxidant could reduce reaction time and improve product yield. Microwave
      irradiation was an advisable choice for treating organic wastewaters and has a
      widely application perspective for non- or low-transparent and fuscous dye
      wastewaters.

PMID- 17512660
TI  - Does the medial thalamus play a role in the negative affective component of
      visceral pain in rats?
AB  - Pain consists of sensory and negative affective components. Using a conditioned
      place aversion (CPA) paradigm, we investigated whether the medial thalamus (MT)
      played a role in the affective component of visceral pain induced by
      intraperitoneal injection of acetic acid into male Long-Evan rats. Acetic acid
      produced writhing response as well as CPA. The bilateral MT-lesions resulted in
      slight reduction of writhing response, but CPA was not affected. The results
      suggest that while MT may play a role in visceral nociception, it does not
      participate in the negative affective component of visceral pain.

PMID- 17512661
TI  - Diffusion tensor imaging demonstrates focal lesions of the corticospinal tract in
      hemiparetic patients with cerebral palsy.
AB  - The purpose of this study was to use diffusion tensor imaging (DTI) with fiber
      tractography (FT) to demonstrate focal lesions of the corticospinal tract (CST)
      in hemiparetic patients with cerebral palsy (CP) who showed no specific focal
      lesions on conventional brain MRI. Four hemiparetic patients with CP (three left
      hemiparesis, mean age: 2.5 years, range: 0.9-7.0) and four age-matched controls
      were recruited. DTI was performed using a 1.5-T system with a synergy-L
      Sensitivity Encoding head coil. Fractional anisotropy (FA) and apparent diffusion
      coefficients (ADC) were measured using the region of interest (ROI) method. We
      estimated the asymmetric anisotropy index (AA) and asymmetric mean diffusivity
      index (AD) to evaluate the asymmetry between right and left CSTs. All four
      patients showed interrupted FT at the affected periventricular white matter
      (PVWM) level compared to that of the opposite side; this was not detected on
      conventional brain MRI and explained the hemiparesis of these patients. Compared
      to the data of controls, all patients showed significant AA and AD only at the
      PVWM level. DTI with FT demonstrated focal lesions at the PVWM level. We conclude
      that DTI with FT may be a useful modality for investigating focal lesions in
      hemiparetic patients with CP.

PMID- 17512662
TI  - Advisory regarding Faces Pain Scale.

PMID- 17512663
TI  - Negative affect, pain and sex: the role of endogenous opioids.
AB  - Opioid neurotransmission modulates pain and negative affect during psychological
      stress. To determine whether these effects differ between men and women, the
      opioid receptor antagonist naltrexone or placebo was administered double-blind to
      21 men and 22 women before they completed 30 min of difficult mental arithmetic.
      To heighten negative affect, participants received seven moderately noxious
      electric shocks during the math task, which were believed to be contingent upon
      performance. Before and after the math task, participants rated pain intensity
      and unpleasantness while their left hand was immersed in 2 degrees C water for up
      to 4 min. Anxiety, discouragement and anger were also rated before, during and
      after the math task. Tolerance of cold-induced pain was greater in men, whereas
      discouragement during the math task was greater in women. Opioid blockade did not
      influence ratings of negative affect, which increased in line with the intensity
      and unpleasantness of shock-induced pain. The intensity and unpleasantness of
      cold-induced pain increased after the math task only in women administered
      naltrexone. Within the naltrexone condition, pain ratings increased most in the
      most discouraged subjects. However, this relationship was absent in placebo
      recipients, implying that the hyperalgesic effect of psychological distress was
      tempered by opioid release. Greater stress-evoked discouragement in women than
      men may explain why cold-induced pain increased after the math task only in women
      administered naltrexone.

PMID- 17512665
TI  - Peripherally-triggered CRPS and dystonia.

PMID- 17512666
TI  - New advances in pathophysiology of PHN: are they clinically relevant?

PMID- 17512667
TI  - The importance of family environment for young adults burned during childhood.
AB  - This study examined the role of family environment for young adult burn survivors
      making the transition from adolescence to adulthood. Ninety-three young adults
      who sustained large burns as children were asked to describe their families using
      the Family Environment Scale (FES). When examining the difference between burn
      survivors and the normative sample of the FES, burn survivors did not perceive
      their current family environment different than the normative group. However,
      burn survivors endorsed more items in the areas of achievement orientation and
      moral-religious emphasis, and less involvement in intellectual-cultural
      activities. We also examined the relationship between family characteristics on
      the FES and psychological adjustment of burn survivors as measured by the Young
      Adult Self-Report (YASR). Increased conflict on the FES was positively associated
      with YASR total problem score, internalizing behaviors, and externalizing
      behaviors. In addition, participation in recreational and social activities and
      organization both inversely correlated with YASR total problem score. In
      conclusion, increased family conflict was associated with decreased psychological
      adjustment of burn survivors as measured by the YASR total problem score.

PMID- 17512668
TI  - The use of aquacel Ag in the treatment of partial thickness burns: a national
      study.

PMID- 17512669
TI  - Seeding following percutaneous diagnostic and therapeutic approaches for
      hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for
      percutaneous approach of HCC.
AB  - BACKGROUND: Tumour biopsy is usually considered mandatory for patient management
      by oncologists. Currently percutaneous ablation is used therapeutically for
      cirrhotic patients with small hepatocellular carcinoma (HCC), not suitable for
      resection or waiting for liver transplantation. However malignant seeding is a
      recognized complication of both diagnostic and therapeutic procedures in patients
      with HCC. Although percutaneous therapy whether with or without biopsy of a
      suspected HCC nodule may minimize the risk of seeding, this has not been
      confirmed. AIM: To evaluate the risk of seeding, defined as new neoplastic
      disease occurring outside the liver capsule, either in the subcutaneous tissue or
      peritoneal cavity following needle biopsy and/or local ablation therapy (LAT).
      METHODS: A literature search resulted in 179 events in 99 articles between
      January 1983 and February 2007: 66 seedings followed liver biopsy, 26
      percutaneous ethanol injection (PEI), 1 microwave, 22 radiofrequency ablation
      (RFA), and 64 after combined biopsy and percutaneous treatment (5 microwave; 33
      PEI; 26 RFA). RESULTS: In 41 papers specifying the total number of patients
      biopsied and/or treated, the median risk of seeding was 2.29% (range 0-11%) for
      biopsy group; 1.4% (1.15-1.85%) for PEI when used with biopsy and 0.61% (0-5.56%)
      for RFA without biopsy, 0.95% (0-12.5%) for RFA with biopsy and 0.72% (0-10%) for
      liver nodules (including non-HCC nodules) biopsied and ablated. CONCLUSION: Risk
      of seeding with HCC is substantial and appears greater with using diagnostic
      biopsy alone compared to therapeutic percutaneous procedures. This risk is
      particularly relevant for patients being considered for liver transplantation.

PMID- 17512670
TI  - Induction and selective accumulation of mutant ubiquitin in CA1 pyramidal neurons
      after transient global ischemia.
AB  - Accumulation of mutant ubiquitin-B (UBB(+1)) in neurons is considered the
      hallmark of proteasomal dysfunction in neurodegenerative disorders, however no
      such evidence in ischemic brain has been reported. We investigated the
      contribution of UBB(+1) in delayed neuronal death after transient global
      ischemia. Transient global ischemia was achieved by occlusion of bilateral common
      carotid arteries for 5 min and reperfusion in male Mongolian gerbils (n=6 per
      each time point). In the CA1 region, UBB(+1) immunoreactivity appeared in the
      cytoplasm of pyramidal cells at 30 min post-ischemia, and the density of these
      neurons increased at day 2 (P<0.001) and further increased at day 4 post
      ischemia. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick
      end labeling (TUNEL)-positive (apoptotic) cells appeared selectively in the CA1
      region at day 3 and their density increased further at day 4 post-ischemia
      (P<0.001). In contrast, UBB(+1) immunoreactivity was only transiently detected
      from 30 min to 1 day post-ischemia in CA3, dentate gyrus, and frontal cortex, but
      disappeared at day 2 post-ischemia. No TUNEL-positive cells were observed in
      these three regions. UBB(+1) mRNA was detected by reverse transcription
      polymerase chain reaction in every region of the hippocampus and frontal cortex
      of ischemic gerbils and even in the non-ischemic control animals, and its
      expression level was independent of brain region and time after ischemia. Our
      results indicate induction and selective accumulation of UBB(+1) protein in dying
      neurons of the CA1 region and suggest that UBB(+1) expression may be induced by
      proteasomal dysfunction after transient global ischemia.

PMID- 17512671
TI  - Phenotypic characterization of spatial cognition and social behavior in mice with
      'knockout' of the schizophrenia risk gene neuregulin 1.
AB  - Neuregulin-1 (NRG1) has been identified as a candidate susceptibility gene for
      schizophrenia. In the present study the functional role of the NRG1 gene, as it
      relates to cognitive and social processes known to be disrupted in schizophrenia,
      was assessed in mice with heterozygous deletion of transmembrane (TM)-domain NRG1
      in comparison with wildtypes (WT). Social affiliative behavior was assessed using
      the sociability and preference for social novelty paradigm, in terms of time
      spent in: (i) a chamber containing an unfamiliar conspecific vs. an empty chamber
      (sociability), or (ii) a chamber containing an unfamiliar conspecific vs. a
      chamber containing a familiar conspecific (preference for social novelty). Social
      dominance and aggressive behavior were examined in the resident-intruder
      paradigm. Spatial learning and memory were assessed using the Barnes maze
      paradigm, while spatial working memory was measured using the continuous variant
      of the spontaneous alternation task. Barnes maze data revealed intact spatial
      learning in NRG1 mutants, with elevated baseline latency to enter the escape hole
      in male NRG1 mutants reflecting an increase in activity level. Similarly,
      although a greater number of overall arm entries were found, spontaneous
      alternation was unaffected in NRG1 mice. Social affiliation data revealed NRG1
      mutants to evidence a specific loss of WT preference for spending time with an
      unfamiliar as opposed to a familiar conspecific. This suggests that NRG1 mutants
      show a selective impairment in response to social novelty. While spatial learning
      and working memory processes appear intact, heterozygous deletion of TM-domain
      NRG1 was associated with disruption to social novelty behavior. These data inform
      at a novel phenotypic level on the functional role of this gene in the context of
      its association with risk for schizophrenia.

PMID- 17512672
TI  - Effect of hypoxia on the morphology of mouse striatal neurons.
AB  - Symptoms of high altitude sickness including headache and neuropsychological
      dysfunction are thought to result from prolonged exposure to hypoxia. In order to
      explain how the brain adapts to lower oxygen pressure at high altitude, CD1 mice
      were exposed to 3 weeks of hypobaric hypoxic conditions. Analyses of the neuronal
      morphology of striatal medium spiny neurons (MSNs) revealed a significant
      decrease in dendritic length, yet no change in dendritic volume, in hypoxic mice
      relative to normoxic mice. Vascular data indicated an increase in blood vessel
      area in the striatum of mice exposed to prolonged hypoxia. A mouse model of high
      altitude exposure may assist in elucidating the mechanisms of cerebral adaptation
      to high altitudes in humans, and therefore aid in developing successful
      prevention techniques and treatment of problems associated with high altitude
      disease.

PMID- 17512674
TI  - Ganglioside 9-O-acetyl GD3 expression is upregulated in the regenerating
      peripheral nerve.
AB  - Evidence accumulates suggesting that 9-O-acetylated gangliosides, recognized by a
      specific monoclonal antibody (Jones monoclonal antibody), are involved in
      neuronal migration and axonal growth. These molecules are expressed in rodent
      embryos during the period of axon extension of peripheral nerves and are absent
      in adulthood. We therefore aimed at verifying if these molecules are re-expressed
      in adult rats during peripheral nerve regeneration. In this work we studied the
      time course of ganglioside 9-O-acetyl GD3 expression during regeneration of the
      crushed sciatic nerve and correlated this expression with the time course of
      axonal regeneration as visualized by immunohistochemistry for neurofilament 200
      in the nerve. We have found that the ganglioside 9-O-acetyl GD3 is re-expressed
      during the period of regeneration and this expression correlates spatio
      temporally with the arrival of axons to the lesion site. Confocal analysis of
      double and triple labeling experiments allowed the localization of this
      ganglioside to Schwann cells encircling growing axons in the sciatic nerve.
      Explant cultures of peripheral nerves also revealed ganglioside expressing
      reactive Schwann cells migrating from the normal and previously crushed nerve.
      Ganglioside 9-O-acetyl GD3 is also upregulated in DRG neurons and motoneurons of
      the ventral horn of spinal cord showing that the reexpression of this molecule is
      not restricted to Schwann cells. These results suggest that ganglioside 9-O
      acetyl GD3 may be involved in the regrowth of sciatic nerve axons after crush
      being upregulated in both neurons and glia.

PMID- 17512675
TI  - Dopamine D2 receptor stimulation inhibits cold-initiated thermogenesis in brown
      adipose tissue in conscious rats.
AB  - Dopamine D(2)-like receptor agonists cause hypothermia. We investigated whether
      inhibiting heat production by interscapular brown adipose tissue (iBAT), a major
      thermogenic organ in rats, contributes to hypothermia caused by dopamine D(2)
      like receptor agonists. Temperature of iBAT and tail artery blood flow were
      measured in conscious rats. Activity in postganglionic sympathetic nerves
      supplying iBAT was assessed in anesthetized rats. Conscious rats were housed in a
      warm cage maintained at 26-28 degrees C and then transferred to a cold cage at 5
      10 degrees C to induce iBAT thermogenesis. Cold exposure increased iBAT
      temperature (+0.7+/-0.1 degrees C, 30 min after transferring to the cold cage,
      P<0.01, n=54). The mixed dopamine D(2)/D(3) receptor agonist, 7-hydroxy-2-(di-n
      propylamino)tetralin (7-OH-DPAT, 0.5 mg/kg s.c.) reversed the cold-induced
      increase in iBAT temperature (-2.8+/-0.2 degrees C at 30 min after 7-OH-DPAT
      treatment during cold exposure vs. +0.3+/-0.1 degrees C at 30 min after vehicle
      treatment during cold exposure, n=8). These temperature changes were blocked by
      pre-treatment with the D(2) receptor antagonists spiperone (20 microg/kg i.p.)
      and L-741,626 (2.5 mg/kg i.p.), but not by the selective D(3) receptor antagonist
      SB-277011A (10 mg/kg i.p.). Another mixed dopamine D(2)/D(3) receptor agonist,
      quinpirole (0.5 mg/kg s.c.) also reversed cold-induced iBAT thermogenesis, and
      this effect was also prevented by pre-treatment with spiperone, but not with a
      peripherally acting dopamine receptor antagonist, domperidone (2 mg/kg s.c.).
      Neither 7-OH-DPAT nor quinpirole reversed cutaneous vasoconstriction elicited by
      cold exposure. In anesthetized rats, quinpirole (0.5 mg/kg i.v.) abolished iBAT
      sympathetic nerve discharge elicited by cooling the trunk, and this change was
      reversed by spiperone (20 microg/kg i.v.). These results demonstrate that
      activation of CNS dopamine D(2) receptors inhibits sympathetically-mediated iBAT
      thermogenesis in response to cold exposure. Furthermore, they suggest that in
      rats hypothermia induced by dopamine D(2) receptor agonists in cold environments
      is mainly due to decreased heat production rather than to increased heat loss.

PMID- 17512676
TI  - Temporal lobe epilepsy is a disease of faulty neuronal resonators rather than
      oscillators, and all seizures are provoked, usually by stress.
AB  - Temporal lobe epilepsy (TLE) is the most common cause of intractable adult
      epilepsy. It is proposed that different kinds of epilepsy be classified into one
      of two categories, which correspond to the two basic kinds of neurons in the
      brain, that is, as diseases of oscillators or as diseases of resonators.
      Oscillator (or pacemacker) neurons are endowed with intrinsic conductances that
      permit periodic spontaneous generation of action potentials; in contrast,
      resonators are neurons which process information coming from sensory stimuli or
      from other neurons. A literature review supports the idea that TLE is a disease
      of faulty resonators. This means that seizures do not arise de novo in the
      seizure focus. The seizure focus responds to normal input with an abnormally
      large discharge that causes seizures. The most frequent trigger for TLE is
      psychological stress. A previously published theory of stress is reviewed. The
      stress circuit runs from the hippocampus to the amygdala to the dorsal raphe
      nucleus to the entorhinal cortex and back to the hippocampus. Cell loss in the
      dentate is central to the pathophysiology of both chronic stress and TLE, which
      establish a "vicious circle" relationship with one another. Once it is grasped
      that TLE is a disease of resonators and that all seizures in TLE are triggered,
      then it makes sense to address the major recognized trigger, which is stress. New
      therapeutic ideas for decreasing seizure frequency in TLE include the use of anti
      depressants, ethosuximide (which blocks firing in the dorsal raphe nucleus), and
      mood-stabilizers (which block firing in the entorhinal cortex). The latter
      category includes several recognized anti-epileptic drugs. Drugs from all three
      categories should be used simultaneously and on an empirical basis in each
      patient.

PMID- 17512677
TI  - Did the first virus self-assemble from self-replicating prion proteins and RNA?
AB  - DNA is the molecule responsible for storing and processing genetic information
      today. In Earth's primeval environmental conditions, RNA was probably more suited
      for this function, due to its capability to act also as a catalytic enzyme. Some
      proteins are stable and reliable molecules even in extreme conditions, and under
      certain circumstances, proteins may play a role in transmitting certain
      phenotypes that are inherited in a non-Mendelian manner. When the dominant native
      state of a prion protein is replaced by a misfolded one, the resultant infective
      protein is associated with several neurological diseases in mammals. The
      misfolded proteins are remarkably resistant to even the most extreme
      environments. Prions are also associated with the transmission of certain fungal
      traits epigenetically, supporting the hypothesis that prions are a possible relic
      of an early stage of peptide evolution. The primitive world probably contained
      both self-replicating RNA molecules and prions, and prions attach easily to
      nucleic acids, and also fold and cause other proteins to fold in the same way.
      Consequently, a capsid could form from prion protein, enclosing the RNA, and
      perhaps creating the first RNA virus. A capsid originating from prion proteins
      would be a versatile and effective protection to RNA and could also explain some
      characteristics of virus self-assembly that are not well understood.

PMID- 17512678
TI  - A simple and effective treatment for stuttering: speech practice without
      audience.
AB  - On the assumption that stuttering is essentially acquired behavior, it has been
      concluded that speech-related anticipatory anxiety as a major cause of stuttering
      accounts for virtually all apparently-different aspects of stuttering on the
      behavioral level. Stutterers' linguistic competence is unimpaired, although their
      speech production is characterized as "disfluent". Yet, such disfluency is
      dramatically reduced when such people speak in anxiety-free no-audience
      conditions. Furthermore, our pilot study of oral reading in Japanese indicates
      that a stutterer can easily replace stuttering events with a common interjection,
      "eh", and make oral reading sound natural and fluent. Given these facts, we
      propose the Overlearning Fluency when Alone (OFA) treatment, consisting of two
      distinct but overlapping steps: (1) Overlearning of fluency in a no-audience
      condition, and (2) Use of an interjection, "eh", as a starter when a stuttering
      event is anticipated. It remains to be demonstrated that this is a truly simple
      and effective treatment for "one of mankind's most baffling afflictions".

PMID- 17512679
TI  - Induction of flavonoid production by UV-B radiation in Passiflora quadrangularis
      callus cultures.
AB  - Callus cultures from several species of Passiflora were initiated in vitro, and
      their capacity to produce four glycosyl flavonoids (orientin, isoorientin,
      vitexin, isovitexin) was analysed. The aim of the present work was to examine the
      possible role of UV-B irradiation and elicitation with methyl jasmonate (MJ) on
      the production of these compounds in callus cultures. All the species tested (P.
      incarnata, P. quadrangularis, P. edulis) formed friable callus from leaf explants
      after 4 weeks on medium supplemented with kinetin and 2,4-dichlorophenoxyacetic
      acid. Among them, P. quadrangularis turned out to have a faster growth rate and a
      more friable texture, and was therefore chosen for experiments with elicitors. In
      callus cultures only small amounts of isoorientin were found, while the
      concentration of the other flavonoids was below the detection limit. UV-B
      irradiation of calluses was able to increase the production of all four glycosyl
      flavonoids. After a 7-day exposure of cultures to UV-B light, the production of
      isoorientin reached concentrations similar to those found in fresh leaves from
      glasshouse-grown plants. Elicitation with methyl jasmonate also enhanced
      orientin, vitexin and isovitexin concentrations, even though the stimulation was
      about 6-fold weaker for orientin and vitexin and about 40-fold for isovitexin,
      than that exerted by UV-B treatment. Callus cultures treated with the UV-B dose
      which most enhanced flavonoid production showed a higher antioxidant activity
      compared to untreated calluses, with an increase ranging from 28% to 76%. Results
      show that the secondary metabolite biosynthetic capacity of Passiflora tissue
      cultures can be enhanced by appropriate forms of elicitation.

PMID- 17512680
TI  - Cytotoxic activity of lignans from Hibiscus cannabinus.
AB  - The antimicrobial and cytotoxic activities of six lignans isolated from the core
      and bark acetone extracts of Hibiscus cannabinus have been investigated. Two
      compounds (2 and 3) showed strong cytotoxic activity against HeLa, Hep-2 and A
      549 cell lines while compound 5 showed moderate activity on HeLa cells when they
      were in advanced stage of cellular division. The compounds did not exhibit
      antimicrobial activity.

PMID- 17512681
TI  - Repellent activity of selected essential oils against Aedes aegypti.
AB  - Essential oils extracted from ten plant species were screened for repellency
      against Aedes aegypti mosquitoes. Three oils; Zanthoxylum piperitum, Anethum
      graveolens and Kaempferia galanga, exerted protection against A. aegypti, with
      median complete-protection times of 1, 0.5 and 0.25 h, respectively. The
      protection times were increased significantly by incorporating 10% vanillin. The
      highest potential was established from Z. piperitum oil +10% vanillin (2.5 h,
      range=1-2.5 h). Mixtures from pairs of the effective oils possessed slight
      repellency that ranged from 0-0.5 h. None of the oil combinations repelled A.
      aegypti for longer than their constituent oil alone. With vanillin added,
      however, each oil mixture provided improved protection, which was approximately
      equal to oil on its own. GC/MS analysis revealed that the main component of Z.
      piperitum fruit oil was limonene (37.99%), with minor amounts of sabinene
      (13.30%) and beta-myrcene (7.17%). Repellent testing of stored samples of Z.
      piperitum fruit oil against A. aegypti demonstrated that repellent activity of
      those kept at -20 degrees C or 4 degrees C was present for a period of at least 3
      months. Therefore, the essential oil of Z. piperitum fruit may prove useful in
      the development of mosquito repellents as an effective personal protection
      measure against mosquito bites.

PMID- 17512682
TI  - The latent structure of marijuana and cocaine use disorders: results from the
      National Longitudinal Alcohol Epidemiologic Survey (NLAES).
AB  - To better understand the underlying concepts of substance dependence and abuse,
      the present study examines the factor structure of DSM-IV lifetime criteria for
      cannabis and cocaine use disorders. Data for this study were drawn from the
      National Longitudinal Alcohol Epidemiologic Survey (NLAES), a large nationally
      representative U.S. sample aged 18 years and older. Exploratory factor analysis
      (EFA) examined the factor structure for each substance and the factors were
      related to background covariates using latent variable modeling techniques.
      Separate analyses were conducted for lifetime marijuana and cocaine users. A two
      factor solution was identified for each substance and was similar to DSM-IV abuse
      and dependence. The factors were highly correlated for both cannabis (r=0.73) and
      cocaine (r=0.77). Background variables accounted only for a modest amount of
      factor variance. In conjunction with the findings in alcohol use disorders, these
      results support the use of consistent criteria across substances in DSM-IV and
      ICD-10, and suggest that the consistent finding of two correlated factors across
      substances needs to be better understood.

PMID- 17512683
TI  - Chronic hypoxia differentially increases glutathione content and gamma-glutamyl
      cysteine synthetase expression in fetal guinea pig organs.
AB  - OBJECTIVE: Glutathione is a natural antioxidant in the fetus and adult. We sought
      to determine whether maternal hypoxia alters glutathione levels in fetal organs
      as an adaptive response to the reduced oxygenation. STUDY DESIGN: Timed pregnant
      guinea pigs were housed in either a Plexiglas chamber containing 10.5% O(2) from
      46 to 60 days gestation (HPX, n=6) or in room air, as the normoxic control (NMX,
      n=5). Pregnant guinea pigs were anesthetized at near term ( approximately 60
      days, term=65 days) and liver, lungand kidney were excised from anesthetized
      fetuses and stored frozen (-80 degrees C) prior to sample processing. Using the
      hypoxia marker, pimonidazole, we measured a hypoxia-induced increase in stained
      cells of fetal liver compared to no change in either the lung or kidney. To
      measure the effect of hypoxia among different organs, total glutathione (GSH)
      content and protein levels of gamma-glutamyl cysteine synthetase (gamma-GCS) were
      measured from the same organs. RESULTS: Maternal hypoxia increased (P<0.05) total
      glutathione levels by 121% in the fetal liver but had no effect in either fetal
      lung or kidney. Chronic hypoxia increased (P<0.05) gamma-GCS protein levels in
      all three fetal organs studied. CONCLUSION: These results demonstrate that the
      fetal response to maternal hypoxia may be organ specific. The increase in fetal
      liver glutathione via upregulation of gamma-GCS may be an important adaptive
      response to prolonged hypoxic stress.

PMID- 17512684
TI  - The relationship between fetal inferior vena cava diameter pulse and flow
      velocity waveforms in normal and compromised pregnancies.
AB  - BACKGROUND: The circulation is characteristically assessed by pressure and flow.
      OBJECTIVE: To evaluate the hemodynamic significance of fetal inferior vena cava
      (IVC) flow velocity waveform (FVW) indices in relation to the diameter pulse
      waveform (DPW). STUDY DESIGN: Doppler ultrasound and a phase locked loop echo
      tracking system were used to measure the FVW and the DPW in the fetal IVC,
      respectively. SUBJECTS: We studied 98 normal fetuses (20 to 40 weeks) and 65
      compromised fetuses with increased umbilical placental resistance. RESULTS: The
      DPW consisted of four waves (A, X, V, and Y waves). Three components (systolic
      flow; S, diastolic flow; D, reverse flow; R during atrial contraction) were
      identified in the FVW. The FVW indices were examined in relation to the X descent
      {(A - X) / A%} of the DPW. The compromised group was divided into three subgroups
      by the X descent. In 15 fetuses the waveform was normal. In 32 there was a high
      pulsatile pattern with deep descent form the A crest to X trough. In 18 the X
      descent was shallow and the pulsatility appeared reduced. The high and low
      pulsatile patterns were associated with an increase in the S/D ratio and the R/S
      ratio, respectively. CONCLUSION: In fetal compromise the high pulsatility DPW may
      result from increased end-diastolic pressure in response to the increase in
      ventricular afterload caused by the placental vessel obliteration. The S/D ratio
      of the FVW may reflect the increasing cardiac afterload. The low pulsatility DPW
      may indicate depressed myocardial function and output. In the FVW, the R/S ratio
      may be associated with this.

PMID- 17512685
TI  - Preparation and in vitro evaluation of carrier erythrocytes for RES-targeted
      delivery of interferon-alpha 2b.
AB  - Carrier erythrocytes is one of the most promising systemic drug delivery systems
      investigated in recent decades. In this study, human erythrocytes have been
      loaded with interferon-alpha 2b (IFN) with the aim to benefit the
      reticuloendothelial system (RES) targeting potential of the carrier cells.
      Hypotonic preswelling method was used for drug loading in erythrocytes and the
      entire loading procedure was evaluated and validated. The loaded amount,
      entrapment efficiency and cell recovery of the loading procedure were 2906.33+/
      588.35IU/0.1ml, 14.53+/-2.94%, and 83.61+/-0.49%, respectively, all being
      practically feasible. The carrier erythrocytes were characterized in vitro in
      terms of their drug release kinetics, hematological indices, particle size
      distribution, SEM analysis, and osmotic and turbulence fragility. IFN release
      from carrier cells was a relatively rapid process in comparison to the cell lysis
      kinetics, which is unusual considering the whole body of data published on this
      delivery system and other protein drugs, so far. All the tested in vitro
      characteristics showed significant, sometimes notable changes upon drug loading
      procedure, both with and without the drug.

PMID- 17512686
TI  - Characterization of the cultivable microbiota of sprouts and their potential for
      application as protective cultures.
AB  - The microbiota of ten seeds and ready-to-eat sprouts produced thereof was
      characterized by bacteriological culture and denaturing gradient gel
      electrophoresis (DGGE) of amplified DNA fragments of the 16S rRNA gene. The
      predominant bacterial biota of hydroponically grown sprouts mainly consisted of
      enterobacteria, pseudomonades and lactic acid bacteria (LAB). For adzuki,
      alfalfa, mung bean, radish, sesame and wheat, the ratio of these bacterial groups
      changed strongly in the course of germination, whereas for broccoli, red cabbage,
      rye and green pea the ratio remained unchanged. Within the pseudomonades,
      Pseudomonas gesardii and Pseudomonas putida have been isolated and strains of the
      potentially pathogenic species Enterobacter cancerogenes and Pantoea agglomerans
      were found as part of the main microbiota on hydroponically grown sprouts. In
      addition to the microbiota of the whole seedlings, the microbiota of root,
      hypocotyl and seed leafs were examined for alfalfa, radish and mung bean sprouts.
      The highest and lowest total counts for aerobic bacteria were found on seed leafs
      and hypocotyls, respectively. On the other hand, the highest numbers for LAB on
      sprouts were found on the hypocotyl. When sprouting occurred under the
      agricultural conditions, e.g. in soil, the dominating microbiota changed from
      enterobacteria to pseudomonades for mung beans and alfalfa sprouts. No pathogenic
      enterobacteria have been isolated from these sprout types. Within the
      pseudomonades group, Pseudomonas jessenii and Pseudomonas brassicacearum were
      found as dominating species on all seedling parts from soil samples. In practical
      experiments, a strain of P. jessenii was found to exhibit a potential for use as
      protective culture, as it suppresses the growth of pathogenic enterobacteria on
      ready-to-eat sprouts.

PMID- 17512687
TI  - Reliable HPLC method for therapeutic drug monitoring of frequently prescribed
      tricyclic and nontricyclic antidepressants.
AB  - A new high-performance liquid chromatography method is presented for the
      determination of 10 frequently prescribed tricyclic and nontricyclic
      antidepressants: imipramine, amitriptyline, clomipramine, fluoxetine, sertraline,
      paroxetine, citalopram, mirtazapine, moclobemide and duloxetine. The simple and
      accurate sample preparation step, consisted of liquid:liquid extraction with
      recoveries ranging between 72% and 86%, except for moclobemide (59%). Separation
      was obtained using a reverse phase Select B column under isocratic conditions
      with UV detection (230 nm). The mobile phase consisted of 35% of a mixture of
      acetonitrile/methanol (92:8, v/v) and 65% of 0.25 mol L(-1) sodium acetate
      buffer, pH 4.5. The standard curves were linear over a working range of 2.5-1000
      ng mL(-1) for moclobemide, 5-2000 ng mL(-1) for citalopram, duloxetine,
      fluoxetine, 10-2000 ng mL(-1) for sertraline, imipramine, paroxetine, mirtazapine
      and clomipramine. The intra-assay and inter-assay precision and accuracy were
      studied at three concentrations (50, 200, and 500 ng mL(-1)). The intra-assay
      coefficients of variation (CVs) for all compounds were less than 8.8%, and all
      inter-CVs were less than 10%. Limits of quantification were 2.5 ng mL(-1) for
      moclobemide, 5 ng mL(-1) for citalopram, duloxetine and amitriptyline, and 10 ng
      mL(-1) for mirtazapine, paroxetine, imipramine, fluoxetine, sertraline, and
      clomipramine. No interference of the drugs normally associated with
      antidepressants was observed. The method has been successfully applied to the
      analysis of real samples, for the drug monitoring of ten frequently prescribed
      tricyclic and non-tricyclic antidepressant drugs.

PMID- 17512688
TI  - Development and validation of a rapid HPLC method for the determination of
      oseltamivir phosphate in Tamiflu and generic versions.
AB  - Oseltamivir phosphate (OP) is an antiviral drug that is used in the treatment and
      prophylaxis of both influenza A and influenza B. It is effective against all
      known influenza viruses than can infect humans, including pandemic influenza
      viruses and may be the most appropriate antiviral option against avian influenza
      caused by H5N1 virus. Tamiflu, the registered trademark used under exclusive
      license by Roche laboratories with OP as active pharmaceutical ingredient, is
      considered the best treatment for the bird flu disease. A simple, selective,
      linear, accurate and precise HPLC method was developed and validated for rapid
      assay of OP aimed to the quality control of Tamiflu capsules and generic
      versions. Isocratic elution at a flow rate of 1.2 mL/min was employed on a Zorbax
      CN column (150 mm x 4.6mm; 5 microm) at ambient temperature. The mobile phase
      consisted of methanol and 0.04 M formic acid pH 3.0 (50:50, v/v). The UV
      detection wavelength was 226 nm and 20 microL of sample was injected. Sotalol
      hydrochloride was used as the internal standard (IS). The retention times for OP
      and IS were 3.40 and 2.25 min, respectively. The method was successfully applied
      to commercial pharmaceuticals, Tamiflu and generic versions. The proposed method
      could be applicable for routine analysis of OP and monitoring of the quality of
      marketed drugs as possibly counterfeit Tamiflu.

PMID- 17512689
TI  - Separation and determination of flavonoids in Lamiophlomis rotata by capillary
      electrophoresis using borate as electrolyte.
AB  - A capillary electrophoresis method was developed for the simultaneous
      determination of five flavonoids such as luteolin-7-O-glucoside, isorhamnetin,
      apigenin, luteolin and quercetin in Lamiophlomis rotata (Benth.) Kudo. Optimal
      conditions were obtained at pH 9.0 with 30 mM borate as buffer containing 8%
      (v/v) acetonitrile, 20 kV as driving voltage and 210 nm as detection wavelength.
      The association constant K and the change in Gibbs free energy (DeltaG) of the
      interaction of flavonoids with borate anion ion (a typical ion-dipole or ion
      induced dipole interaction) were calculated for the quantitative evaluation and
      characterization of the interaction. The described method was successfully
      applied for the rapid and efficient quality control by quantifying flavonoids in
      L. rotata. Repeatability tests showed that the R.S.D.s of both intra- and inter
      day migration times and peak areas were less than 5%. The LOD of the five
      flavonoids was less than 3.75 mg/l. Recovery results ranged from 94.2% to 105.1%.

PMID- 17512690
TI  - Quantitative determination of 1-deoxynojirimycin in mulberry leaves using liquid
      chromatography-tandem mass spectrometry.
AB  - A novel HPLC-MS/MS method was developed for the quantitative determination of 1
      deoxynojirimycin (DNJ), a potent glucosidase inhibitor present in mulberry leaves
      (Morus alba L.). DNJ was isolated from the mulberry leave extract on a TSKgel
      Amide-80 column using a mixture of 0.1% formic acid and acetonitrile as a mobile
      phase at a flow rate of 0.6 ml/min. A triple quadrupole mass spectrometry using
      electrospray ionization source in a positive ion mode under multiple reaction
      monitoring with the [M+H]+ ions, m/z 164.4/109.9 was used. The detection limit
      (S/N=3) was 75 pg and quantitation limit (S/N=10) was 100 pg. The comparison of
      mulberry leaves of different ages showed that the DNJ level was higher in
      mulberry shoots than young and mature leaves.

PMID- 17512691
TI  - Continuous wavelet and derivative transforms for the simultaneous quantitative
      analysis and dissolution test of levodopa-benserazide tablets.
AB  - Simultaneous analyses and dissolution tests of levodopa-benserazide tablets were
      carried out by continuous wavelet transform (CWT) and classic derivative
      spectrophotometry (DS) without using any chemical separation step. The developed
      two spectrophotometric resolutions are based on the transformation of the
      original UV spectra. The original absorption spectra of levodopa and benserazide
      in the concentration range of 1-80 microg/mL and 5-240 microg/mL in USP simulated
      gastric juice were registered in the spectral range of 250-310 nm, respectively.
      Various wavelet families and different spectrophotometric derivative orders were
      tested to find the optimal signal processing for obtaining desirable calibration
      graphs and reliable determinations of the investigated drugs. Under the optimized
      conditions of the methods, symlets wavelet family using a=128 with sixth order
      (SYM6-CWT) and the first derivative transform with Deltalambda=10nm were
      identified as optimal signal processing methods for the determinations and
      dissolution tests. The calibration functions for each drug were obtained by
      measuring the values of the CWT and derivative amplitudes. The validation of the
      developed methods was confirmed by analyzing various synthetic mixtures of the
      investigated drugs. Mean recovery values were found between 99.1% and 104.7% for
      DS and 100% and 102.9% for CWT, respectively for determination of BEN and LEV in
      synthetic mixtures. Each developed approaches were successfully applied to the
      simultaneous determination and dissolution test of levodopa and benserazide in
      their commercial tablets and a good agreement was observed.

PMID- 17512692
TI  - Quality assessment of Rhizoma et Radix Notopterygii by HPTLC and HPLC
      fingerprinting and HPLC quantitative analysis.
AB  - This paper describes an improved quality assessment method for Rhizoma et Radix
      Notopterygii (the rhizome and root of Notopterygium incisum Ting ex H.T. Chang or
      Notopterygium forbesii Boiss). The method was established by using fingerprinting
      and quantitation of marker compounds (isoimperatorin, notopterol and bergapten)
      in this herbal medicine. The authentication of Rhizoma et Radix Notopterygii
      using high performance thin-layer chromatography (HPTLC) fingerprinting was
      achieved by comparing the colors and Rf values of the bands in TLC fingerprints
      with those of the marker compounds. The HPLC fingerprints of 16 batches of herbal
      samples from different regions of China showed similar chromatographic patterns.
      Five peaks were selected as characteristic peaks, and three of these were
      identified by using LC-MS-MS techniques. The relative retention times of these
      characteristic peaks in the HPLC fingerprint were established as an important
      parameter for identification of Rhizoma et Radix Notopterygii. Finally, the
      pharmacologically active marker compounds isoimperatorin, notopterol and
      bergapten in this herb were quantitatively determined using a validated reverse
      phase HPLC method.

PMID- 17512693
TI  - Fingerprint analysis of fruiting bodies of cultured Cordyceps militaris by high
      performance liquid chromatography-photodiode array detection.
AB  - We have developed and optimized a novel, efficient and accurate fingerprint
      method using high-performance liquid chromatography-photodiode array detection
      (HPLC-DAD) for the quality control of cultured Cordyceps militaris (L.) Link. The
      feasibility and advantages of the used chromatographic fingerprint were verified
      for the evaluation of cultured C. militaris by systematically comparing
      chromatograms with a professional analytical software recommended by State Food
      and Drug Administration (SFDA) of PR China. The results revealed that the
      chromatographic fingerprint combining similarity evaluation could efficiently
      identify and distinguish cultured C. militaris from different sources.

PMID- 17512694
TI  - Comparison of cytotoxicity and genotoxicity induced by the extracts of methanol
      and gasoline engine exhausts.
AB  - Gasoline engine exhaust has been considered a major source of air pollution in
      China, and methanol is considered as a potential substitute for gasoline fuel. In
      this study, the genotoxicity and cytotoxicity of organic extracts of condensate,
      particulate matters (PM) and semivolatile organic compounds (SVOC) of gasoline
      and absolute methanol engine exhaust were examined by using MTT assay,
      micronucleus assay, comet assay and Ames test. The results have showed that
      gasoline engine exhaust exhibited stronger cytotoxicity to human lung carcinoma
      cell lines (A549 cell) than methanol engine exhaust. Furthermore, gasoline engine
      exhaust increased micronucleus formation, induced DNA damage in A549 cells and
      increased TA98 revertants in the presence of metabolic activating enzymes in a
      concentration-dependent manner. In contrast, methanol engine exhaust failed to
      exhibit these adverse effects. The results suggest methanol may be used as a
      cleaner fuel for automobile.

PMID- 17512695
TI  - Protective effect of vitamin C 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 vitamin C
      towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis
      (SCGE)/HepG2 assay. None of the vitamin C concentrations tested (1-10 microM) in
      presence or absence of formamidopyrimidine-DNA glycosylase (Fpg enzyme) caused
      DNA damage per se. HepG2 cells simultaneously treated with vitamin C and N
      nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrosodibutylamine
      (NDBA) or N-nitrosopiperidine (NPIP) reduced the genotoxic effects of the N
      nitrosamines in a dose-dependent manner. At concentrations of 1-5 microM vitamin
      C, the protective effect was higher towards NPYR-induced oxidative DNA damage (78
      79%) than against NDMA (39-55%), NDBA (12-14%) and NPIP (3-55%), in presence of
      Fpg enzyme. However, a concentration of 10 microM vitamin C led to a maximum
      reduction in NDBA (94%), NPYR (81%), NPIP (80%) and NDMA (61%)-induced oxidative
      DNA damage, in presence of Fpg enzyme. The greatest protective effect of vitamin
      C (10 microM) was higher towards NDBA-induced oxidative DNA damage. One feasible
      mechanism by which vitamin C exerted its protective effect is that may interact
      with the enzyme systems catalyzing the metabolic activation of the N
      nitrosamines, blocking the production of genotoxic intermediates. Vitamin C (10
      microM) strongly reduced the coumarin hydroxylase (82%) activity. However, the p
      nitrophenol hydroxylase and the ethoxyresorufine O-deethylation activities were
      slightly and weakly reduced (32-19%), respectively.

PMID- 17512696
TI  - Polychlorinated biphenyl exposure and CYP19 gene regulation in testicular and
      adrenocortical cell lines.
AB  - Exposure to polychlorinated biphenyls (PCBs) disturbs many estrogen-mediated
      biochemical processes. PCBs may cause these abnormalities by altering expression
      of the aromatase gene CYP19. This study demonstrated that high concentrations of
      PCB126 increased basal CYP19 mRNA abundance in mouse testicular Leydig I-10 cells
      and human adrenocortical H295R cells. Stimulating the cells with chorionic
      gonadotropin or 8-Br-cAMP concealed the estrogenic effect of PCB126. PCB126 is a
      powerful ligand for nuclear receptor AhR. Antagonizing the AhR activity of H295R
      by an inhibitor abolished PCB126-elicited CYP19 induction. However, PCB126
      elevated basal CYP19 expression and aromatase activity in a slow progressive
      manner contrary to the sharp induction of the classic AhR target gene CYP1A1.
      Exposure of H295R to PCBs with different AhR activation abilities also varied
      CYP19 and CYP1A1 expression in dissimilar patterns, although the CYP19 mRNA
      levels were in line with the AhR activation abilities of the congeners. In
      contrast to PCB126, PCB39, which could not activate AhR and lacked effect on
      CYP1A1, significantly reduced CYP19 mRNA expression. AhR apparently played an
      important role in CYP19 gene regulation, but it might regulate CYP19 differently
      from CYP1A1 in the adrenocortical cells. Regardless of the action mechanism, PCB
      exposure increases risk for CYP19 dysregulation.

PMID- 17512697
TI  - Emotion regulation among individuals classified with and without generalized
      anxiety disorder.
AB  - Generalized anxiety disorder (GAD) has been conceptualized as being characterized
      by the experience of intense emotion, limited understanding of the emotional
      experience, poor ability to adaptively modulate emotions, and an aversive
      response to emotions [Mennin, D. S., Turk, C. L., Heimberg, R. G., & Carmin, C.
      N. (2004). Focusing on the regulation of emotion: a new direction for
      conceptualizing and treating generalized anxiety disorder. In: M. A. Reinecke, &
      D. A. Clark (Eds.), Cognitive therapy over the lifespan: theory, research and
      practice (pp. 60-89). New York: Wiley]. In order to test aspects of this model,
      participants completed daily diaries and a questionnaire measuring emotion
      regulation strategies. As hypothesized, relative to controls, individuals
      classified as having GAD reported more intense daily emotional experiences.
      Contrary to predictions and previous research, those with GAD did not show poor
      emotion differentiation and used several emotion regulation strategies more often
      than control participants. The implications for both the emotion dysregulation
      model and treatment of GAD are discussed.

PMID- 17512698
TI  - Microarray image segmentation using additional dye--an experimental study.
AB  - The DNA microarray technique allows monitoring the expression levels of thousands
      of genes simultaneously. A single DNA microarray experiment involves a number of
      error-prone manual and automated processes, which influence the results and have
      an impact on the subsequent stages of analysis. Typical problems of arrays are
      pinning errors while probe printing and the corruption of spots by noise patches.
      These errors should be detected at the time of image analysis in order to prevent
      the erroneous intensities from ending up in the analysis and inference stages.
      RESULTS: In this paper we introduce the concept (referred to as SybrSpot) of
      utilizing information provided by an additional dye, SYBR green RNA II, for
      segmentation of gene expression microarrays. Owing to the effective binding of
      the SYBR green RNA II to the array probes, an image with high signal-to-noise
      ratio is obtained. This image is used to learn about the spot quality and to flag
      spots which are not reliably hybridized and corrupted by noise. Further, we
      compare SybrSpot with GenePix and demonstrate that SybrSpot performs better than
      GenePix when flagging spots with no probes or weak probes. AVAILABILITY: The code
      is available upon request to authors.

PMID- 17512699
TI  - Nonlinear principal component analysis of noisy data.
AB  - With very noisy data, having plentiful samples eliminates overfitting in
      nonlinear regression, but not in nonlinear principal component analysis (NLPCA).
      To overcome this problem in NLPCA, a new information criterion (IC) is proposed
      for selecting the best model among multiple models with different complexity and
      regularization (i.e. weight penalty). This IC gauges the inconsistency I between
      the nonlinear principal components (u and u) for every data point x and its
      nearest neighbour x, with I=1 - correlation (u, u), where I tends to increase
      with overfitted solutions. Tests were performed using autoassociative neural
      networks for NLPCA on synthetic and real climate data (tropical Pacific sea
      surface temperatures and equatorial stratospheric winds), with the IC performing
      well in model selection and in deciding between an open curve or a closed curve
      solution.

PMID- 17512700
TI  - Regulation of innate immune response by MAP kinase phosphatase-1.
AB  - Mitogen-activated protein (MAP) kinase cascades are signal transduction pathways
      that play pivotal regulatory roles in the biosynthesis of pro-inflammatory
      cytokines. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP
      family, is essential for the dephosphorylation/deactivation of MAP kinases p38
      and JNK. Earlier studies conducted using cultured immortalized macrophages
      provided compelling evidence indicating that MKP-1 deactivates p38 and JNK,
      thereby limiting pro-inflammatory cytokine biosynthesis in innate immune cells
      exposed to microbial components. Recent studies employing MKP-1 knockout mice
      have confirmed the central function of MKP-1 in the feedback control of p38 and
      JNK activity as well as the crucial physiological function of MKP-1 as a negative
      regulator of the synthesis of pro-inflammatory cytokines in vivo. MKP-1 was shown
      to be a major feedback regulator of the innate immune response and to play a
      critical role in preventing septic shock and multi-organ dysfunction during
      pathogenic infection. In this review, we will update the studies on the
      biochemical properties and the regulation of MKP-1, and summarize our
      understanding on the physiological function of this key phosphatase in the innate
      immune response.

PMID- 17512702
TI  - ITGB4 missense mutation in a transmembrane domain causes non-lethal variant of
      junctional epidermolysis bullosa with pyloric atresia.

PMID- 17512701
TI  - Chromosomal abnormality at 6p25.1-25.3 identifies a susceptibility locus for
      hypothalamic hamartoma associated with epilepsy.
AB  - The pathogenesis of hypothalamic hamartoma (HH) associated with epilepsy is
      unknown. We have identified an individual with HH and refractory epilepsy
      exhibiting subtle dysmorphic features. High-resolution karyotype identified a
      duplication of the terminal end of 6p (6p25.1-25.3), confirmed by fluorescent in
      situ-hybridization (FISH). Copy number analysis with high-density (250K) single
      nucleotide polymorphism (SNP) genotyping microarrays characterized the
      abnormality as a series of amplified regions between 1.4 Mb and 10.2 Mb, with a
      small tandem deletion from 8.8 Mb to 9.7 Mb. There are 38 RefSeq genes within the
      duplicated regions, and no known coding sequences within the deletion. This
      unique patient helps identify 6p25.1-25.3 as a possible susceptibility locus for
      sporadic HH.

PMID- 17512703
TI  - In vitro activities of faropenem, ertapenem, imipenem and meropenem against
      Borrelia burgdorferi s.l.
AB  - Little is known about the in vitro activity of penems and carbapenems against the
      spirochete Borrelia burgdorferi. Here, faropenem, ertapenem, imipenem and
      meropenem as well as the third-generation cephalosporin ceftriaxone and
      tobramycin were tested in vitro against 11 isolates of the B. burgdorferi sensu
      lato complex. On a microg/mL basis, ertapenem was the most potent carbapenem
      (minimal inhibitory concentration (MIC) range: 0.015-0.125 microg/mL), with in
      vitro activity comparable with that of ceftriaxone against Borrelia. These
      findings are supported by the results of time-kill experiments in a Borrelia
      afzelii skin isolate, demonstrating a >3 log10 unit (99.9%) reduction of the
      inoculum after 96 h of exposure to either drug at a concentration of three log2
      unit dilutions above the respective MIC.

PMID- 17512704
TI  - Levofloxacin 500 mg once daily versus cefuroxime 250 mg twice daily in patients
      with acute exacerbations of chronic obstructive bronchitis: clinical efficacy and
      exacerbation-free interval.
AB  - The long-term outcome time to relapse determined as the exacerbation-free
      interval (EFI) has been proposed as a standard measure for comparing the efficacy
      of antimicrobial therapies in acute exacerbation of chronic obstructive
      bronchitis (AECOB). In this 6-month, randomised, open-label study, the efficacy
      of 10 days of oral levofloxacin 500 mg once daily or cefuroxime 250 mg twice
      daily was evaluated in 689 well-defined patients experiencing AECOB episodes. In
      the clinically evaluable per-protocol (PPc) population and the modified intent-to
      treat population, the clinical cure rates at test of cure were, respectively,
      94.6% for levofloxacin versus 93.8% for cefuroxime (0.8% difference, 95%
      confidence interval (CI) -3.2 to 4.8) and 94.5% for levofloxacin versus 92.2% for
      cefuroxime (2.3% difference, 95% CI -1.8 to 6.2), whilst the probability that 25%
      of patients would relapse during follow-up was reached within 93 days for
      levofloxacin compared with 81 days for cefuroxime in the PPc population
      (P=0.756). A multivariate analysis revealed that only congestive heart failure
      and number of AECOB episodes in the previous 12 months were predictive of
      relapse. Safety was comparable in the two treatment groups, with possibly related
      treatment-emergent adverse events occurring in 5.0% and 2.9% of subjects in the
      levofloxacin and cefuroxime groups, respectively. In addition to demonstrating
      the non-inferiority of levofloxacin compared with cefuroxime in AECOB, the data
      from this study raise the question of whether EFI is a useful discriminative
      endpoint for comparing antimicrobial therapies.

PMID- 17512705
TI  - How do genes exert their role? Period 3 gene variants and possible influences on
      mood disorder phenotypes.
AB  - The action of multiple liability genes is responsible for complex phenotypes at
      the same time, a single gene, could control several phenotypic features. This is
      the case of human period 3 gene (hper3), mainly involved in the setting of the
      biologic clock. Some variants of this gene, besides being associated with the
      Delayed Sleep Phase Syndrome, showed a key role in determining evening preference
      rather than morning one. According to this rationale, we hypothesized that this
      gene could influence circadian mood fluctuations, in mood disorders. Our study
      demonstrated that rare genetic variants of hper3 are significantly associated to
      a number of mood disorders features, such as age of onset, response to SSRIs
      treatment, circadian mood oscillations and characteristics of temperament. These
      preliminary results could shed further light on the involvement of circadian
      genes in various aspects of physiological and psychopathological mechanisms of
      the brain.

PMID- 17512706
TI  - Auto-orientation of G-wire DNA on mica.
AB  - Scanning probe microscopy was used to examine the orientation of Tet1.5
      quadruplex DNA polymers, a.k.a. "G-wires", after adsorption onto freshly cleaved
      Phyllosilicate micas. The G-wires appear to have a preferential orientation at 60
      degrees intervals after thorough rinsing and slow drying. The angles the G-wires
      made with the fast scan direction of the SPM probe were measured and the
      frequency-angle information was quantitatively characterized by an empirical
      correlation coefficient. Careful measurements indicate the Tet1.5 G-wires orient
      along the b lattice vector of mica, the next nearest neighbor potassium vacancy.
      A model is proposed to explain this auto-orientation affect due to alignment of
      the G-wires' phosphate backbone through magnesium tether cations. Pairs of
      adjacent, parallel phosphate groups of the G-wires (0.95 nm apart) appear to
      align with the next nearest neighbor potassium vacancy sites of mica (0.90 nm
      apart). This behavior is not observed in solution. The potential for using the
      auto-orientation phenomena in the development of high-density biomolecular nano
      electronic devices is explored.

PMID- 17512707
TI  - Three-dimensional fibre-type distribution in the paravertebral muscles of the
      domestic ferret (Mustela putorius f. furo) with relation to functional demands
      during locomotion.
AB  - We investigated the functional corollaries of a relatively long trunk with regard
      to trunk use during overground and underground locomotion and with regard to
      fibre-type distribution within the paravertebral musculature using the example of
      the domestic ferret. Fibre-type distribution was determined using enzyme
      histochemistry on serial cross-sections through the complete musculo-skeletal
      apparatus. Back posture and back movements were analysed using cineradiography.
      During overground locomotion, the back is bent into an arch, resulting in a back
      length comparable to normally proportioned small mammals. During underground
      locomotion, the back is held straight, resulting in greater rotational inertia
      and higher stabilisation requirements. This is reflected in the fibre-type
      distribution pattern, which differs clearly from that of all other mammals
      investigated so far. Instead of being separated into superficial, glycolytic and
      deep, oxidative parts, all the epaxial and the iliopsoas muscles consisted of 20
      30% oxidative, 20-30% oxidative-glycolytic and 40-60% glycolytic fibres, with no
      or only minor differences between superficial and profound muscles or muscle
      regions. Only the quadratus lumborum muscle showed a fibre-type distribution
      comparable to other mammals, reflecting its primary function as an accessory
      muscle of respiration. We suggest that the observed pattern reflects the
      adaptation of the back muscles to the functional demands of a long trunk and the
      increased need to stabilise it during overground and especially underground
      locomotion.

PMID- 17512708
TI  - Argininosuccinate synthetase and argininosuccinate lyase: two ornithine cycle
      enzymes from Agaricus bisporus.
AB  - Accumulation of high quantities of urea in fruiting bodies is a known feature of
      larger basidiomycetes. Argininosuccinate synthetase (ASS) and argininosuccinate
      lyase (ASL) are two ornithine cycle enzymes catalysing the last two steps in the
      arginine biosynthetic pathway. Arginine is the main precursor for urea formation.
      In this work the nucleotide sequences of the genes and corresponding cDNAs
      encoding argininosuccinate synthetase (ass) and argininosuccinate lyase (asl)
      from Agaricus bisporus were determined. Eight and six introns were present in the
      ass and asl gene, respectively. The location of four introns in the asl gene were
      conserved among vertebrate asl genes. Deduced amino acid sequences, representing
      the first homobasidiomycete ASS and ASL protein sequences, were analysed and
      compared with their counterparts in other organisms. The ass ORF encoded for a
      protein of 425 amino acids with a calculated molecular mass of 47266Da. An
      alignment with ASS proteins from other organisms revealed high similarity with
      fungal and mammalian ASS proteins, 61-63% and 51-55% identity, respectively. The
      asl open reading frame (ORF) encoded a protein of 464 amino acids with an
      calculated mass of 52337Da and similar to ASS shared the highest similarity with
      fungal ASL proteins, 59-60% identity. Northern analyses of ass and asl during
      fruiting body formation and post-harvest development revealed that expression was
      significantly up-regulated from developmental stage 3 on for all the tissues
      studied. The expression reached a maximum at the later stages of fruiting body
      growth, stages 6 and 7. Both ass and asl genes were up-regulated within 3h after
      harvest showing that the induction mechanism is very sensitive to the harvest
      event and emphasizes the importance of the arginine biosynthetic
      pathway/ornithine cycle in post-harvest physiology.

PMID- 17512709
TI  - Molecular phylogeny of the genus Lecania (Ramalinaceae, lichenized Ascomycota).
AB  - The molecular phylogeny of the lichen genus Lecania was investigated using
      nucleotide sequences from the mt-SSU rRNA, the ITS region of the nu-rDNA, and the
      RNA polymerase II second largest subunit. Forty-six species representing Lecania
      and other genera likely to influence the phylogeny were included in the study.
      Phylogenetic reconstructions were carried out using Bayesian inference, ML, and
      MP approaches. Lecania, as traditionally circumscribed, is not a monophyletic
      genus. However, a monophyletic group containing a large number of Lecania
      species, including the type species L. fuscella, was discovered in the analysis,
      and recognition of Lecania sensu stricto is suggested. L. baeomma, L. glauca, L.
      gerlachei, L. brialmontii, L. racovitzae, L. hyalina (alias Biatora globulosa),
      L. chlorotiza, L. naegelii, and L. furfuracea do not belong in Lecania s. str.,
      although the latter two are closely related to Lecania s. str. Representatives of
      the genus Bilimbia form a well-supported group, as does the 'Thamnolecania' group
      containing the Antarctic 'Lecania' species, L. gerlachei, L. brialmontii, and L.
      racovitzae. An alternative to recognizing these two genera would be a wider
      circumscription of Bilimbia to include the 'Thamnolecania' group as well as
      affiliated taxa.

PMID- 17512710
TI  - Isoforms of trehalase and invertase of Fusarium oxysporum.
AB  - Enzymatic assays and native PAGE were used to study trehalase and invertase
      activities, depending on culture age and different sugar conditions, in cell-free
      extracts, culture filtrates and ribosomal wash of Fusarium oxysporum. The
      activity of invertase preceded that of trehalase; in the exponential phase of
      growth, mainly invertase activity was produced, whereas trehalase activity was
      high in the stationary phase. In this last phase of growth, the activity of
      intracellular trehalase was repressed by monosaccharides, whereas disaccharides,
      especially lactose and starch, enhanced the activity of intracellular and
      extracellular trehalase. However, invertase activity was not repressed under
      these conditions and had the maximal activity in the presence of saccharose.
      Intracellular trehalase appeared in a single, high-molecular weight (120 kDa)
      form, whereas the extracellular enzyme appeared in a single, low-molecular weight
      (60 kDa) form. The activity pattern of invertase isoforms indicated the
      occurrence of three forms of intracellular enzyme with the main activity band at
      120 kDa and two isoforms of extracellular enzyme. In the ribosomal wash, high
      molecular weight isoforms of both trehalase and invertase were identified. A
      possible role of trehalase and invertase in carbohydrate metabolism of fungal
      pathogens is also discussed.

PMID- 17512711
TI  - Basidiomycete fungal communities in Australian sclerophyll forest soil are
      altered by repeated prescribed burning.
AB  - Soil basidiomycetes play key roles in forest nutrient and carbon cycling
      processes, yet the diversity and structure of below ground basidiomycete
      communities remain poorly understood. Prescribed burning is a commonly used
      forest management practice and there is evidence that single fire events can have
      an impact on soil fungal communities but little is known about the effects of
      repeated prescribed burning. We have used internal transcribed spacer (ITS)
      terminal restriction fragment length polymorphism (T-RFLP) analysis to
      investigate the impacts of repeated prescribed burning every two or four years
      over a period of 30 years on soil basidiomycete communities in an Australian wet
      sclerophyll forest. Detrended correspondence analysis of ITS T-RFLP profiles
      separated basidiomycete communities in unburned control plots from those in
      burned plots, with those burned every two years being the most different from
      controls. Burning had no effect on basidiomycete species richness, thus these
      differences appear to be due to changes in community structure. Basidiomycete
      communities in the unburned control plots were vertically stratified in the upper
      20 cm of soil, but no evidence was found for stratification in the burned plots,
      suggesting that repeated prescribed burning results in more uniform basidiomycete
      communities. Overall, the results demonstrate that repeated prescribed burning
      alters soil basidiomycete communities, with the effect being greater with more
      frequent burning.

PMID- 17512712
TI  - Evidence of mycoparasitism and hypermycoparasitism in Early Cretaceous amber.
AB  - Evidence of mycoparasitism and hypermycoparasitism is demonstrated in Early
      Cretaceous Burmese amber. The agaric, Palaeoagaracites antiquus gen. sp. nov., is
      parasitized by the mycoparasite, Mycetophagites atrebora gen. sp. nov., which in
      turn is parasitized by the hyperparasite, Entropezites patricii gen. sp. nov.
      This discovery shows that sophisticated patterns of fungal parasitism were well
      developed some 100 Myrago.

PMID- 17512713
TI  - Characterization of necrosis and ethylene-inducing proteins (NEP) in the
      basidiomycete Moniliophthora perniciosa, the causal agent of witches' broom in
      Theobroma cacao.
AB  - The hemibiotrophic basidiomycete Moniliophthora perniciosa causes witches' broom
      disease of Theobroma cacao. Analysis of the M. perniciosa draft genome led to the
      identification of three putative genes encoding necrosis and ethylene-inducing
      proteins (MpNEPs), which are apparently located on the same chromosome. MpNEP1
      and 2 have highly similar sequences and are able to induce necrosis and ethylene
      emission in tobacco and cacao leaves. MpNEP1 is expressed in both biotrophic and
      saprotrophic mycelia, the protein behaves as an oligomer in solution and is very
      sensitive to temperature. MpNEP2 is expressed mainly in biotrophic mycelia, is
      present as a monomer in solution at low concentrations (<40 microM) and is able
      to recover necrosis activity after boiling. These differences indicate that
      similar NEPs can have distinct physical characteristics and suggest possible
      complementary roles during the disease development for both proteins. This is the
      first report of NEP1-like proteins in a basidiomycete.

PMID- 17512714
TI  - Evaluation of the potential role of water in spread of conidia of the
      Neotyphodium endophyte of Poa ampla.
AB  - Neotyphodium endophytes are asexual, filamentous fungi, mutualistically
      associated with diverse cool season grasses. Infected seeds and vegetative organs
      of infected host plants are the only known modes of propagation of the asexual
      endophytes. In the last decade certain Epichloe and Neotyphodium-infected grass
      species have been shown to have epiphyllous structures of the endophytes, hyphae,
      conidiophores, and conidia, growing on leaf blades. The production of epiphyllous
      conidia suggests the possibility that some of these endophytes may have the
      ability for plant-to-plant spread. The objective of this study was to determine
      the possible mechanisms involved in liberation and dispersal of asexual spores of
      Neotyphodium growing in vitro and epiphyllously on leaves of Poa ampla. Our
      results indicate that water dispersal is the most likely means of dissemination
      of conidia of the Neotyphodium sp. Wind generated by dry compressed air does not
      dislodge the conidia from slide cultures or from P. ampla leaves.

PMID- 17512715
TI  - Interactions of sterile-cultured lichen-forming ascomycetes with asbestos fibres.
AB  - Sterile cultured isolates of lichen-forming ascomycetes have not yet been used to
      investigate mycobiont-mineral substrate interactions under controlled conditions.
      In this study Candelariella vitellina, Xanthoparmelia tinctina and Lecanora
      rupicola mycobionts were isolated and inoculated with chrysotile fibres in the
      laboratory, in order to verify whether physical and chemical weathering
      processes, which were already described in the field, may be reproduced in vitro.
      Tight adhesion of hyphae to chrysotile fibres was observed in all species. The
      adhering hyphae affected the chemical composition of asbestos fibres, with the
      selective depletion of magnesium being a prominent feature, as is the case in
      field conditions. Oxalic acid and pulvinic acid, mycobiont-derived metabolites of
      X. tinctina and C. vitellina, were involved in the weathering action. Time and
      environmental factors and the absence of biological synergisms strongly limited
      the chemical weathering in vitro compared with what was observed in the field.
      Nevertheless, the results show that in vitro incubation of sterile-cultured
      lichen-forming fungi with minerals is a practicable experimental system to
      investigate the weathering effects of different mycobionts and fungal compounds
      under controlled conditions.

PMID- 17512716
TI  - Thermodynamic analysis of the energy recovery from the aerobic bioconversion of
      solid urban waste organic fraction.
AB  - Waste management is of the utmost importance for many countries and especially
      for highly developed ones due to its implications on society. In particular,
      proper treatment before disposal of the solid urban waste organic fraction is one
      of the main issues that is addressed in waste management. In fact, the organic
      fraction is particularly reactive and if disposed in sanitary landfills without
      previous adequate treatment, a large amount of dangerous and polluting gaseous,
      liquid and solid substances can be produced. Some waste treatment processes can
      also present an opportunity to produce other by-products like energy, recycled
      materials and other products with both economic and environmental benefits. In
      this paper, the aerobic treatment of the organic fraction of solid urban waste,
      performed in a biocell plant with the possibility of recovering heat for civil or
      industrial needs, was examined from the thermodynamic point of view. A
      theoretical model was proposed both for the biological process of the organic
      fraction, as well as for the heat recovery system. The most significant results
      are represented and discussed.

PMID- 17512717
TI  - Improvements of nano-SiO2 on sludge/fly ash mortar.
AB  - Sewage sludge ash has been widely applied to cementitious materials. In this
      study, in order to determine effects of nano-SiO(2) additives on properties of
      sludge/fly ash mortar, different amounts of nano-SiO(2) were added to sludge/fly
      ash mortar specimens to investigate their physical properties and micro
      structures. A water-binding ratio of 0.7 was assigned to the mix. Substitution
      amounts of 0%, 10%, 20%, and 30% of sludge/fly ash (1:1 ratio) were proposed.
      Moreover, 0%, 1%, 2%, and 3% of nano-SiO(2) was added to the mix. Tests,
      including SEM and compressive strength, were carried out on mortar specimens
      cured at 3, 7, and 28 days. Results showed that sludge/fly ash can make the
      crystals of cement hydration product finer. Moreover, crystals increased after
      nano-SiO(2) was added. Hence, nano-SiO(2) can improve the effects of sludge/fly
      ash on the hydration of mortar. Further, due to the low pozzolanic reaction
      active index of sludge ash, early compressive strengths of sludge/fly ash mortar
      were decreased. Yet, nano-SiO(2) could help produce hydration crystals, which
      implies that the addition of nano-SiO(2) to mortar can improve the influence of
      sludge/fly ash on the development of the early strength of the mortar.

PMID- 17512718
TI  - Reusing fly ash in glass fibre reinforced cement: a new generation of high
      quality GRC composites.
AB  - New composite materials based on an alkali-resistant glass-fibre reinforced
      cement (AR-GRC) system are being developed by using fly ash (FA) produced at coal
      thermoelectric power plants, and fluid catalytic cracking catalyst residue (FC3R)
      from the petrol industry as cement replacement materials. These wastes are
      reactive from the pozzolanic viewpoint, and modify the nature and the
      microstructure of the cement matrix when a part of the Portland cement is
      replaced in the formulation of GRC. Several microstructural and mechanical
      aspects are being studied for AR-GRC systems. The behaviour of composites exposed
      to ageing shows that the pozzolanic activity of the ground FA added in high
      amounts and its mixture with the FC3R increase the flexural strength and no
      evidences of strength decay are observed. Additionally, the fibres due to the
      high alkalinity of the cementing matrix can be deteriorated. Fibres in the
      control (only Portland cement) and FC3R containing composites were attacked,
      whereas composites with FA and their mixture with FC3R show that the fibres have
      not been attacked, due to the pozzolanic activity of replacing materials that
      reduce the calcium hydroxide content in the cementing matrix.

PMID- 17512719
TI  - Pretreatment and utilization of waste incineration bottom ashes: Danish
      experiences.
AB  - Within recent years, researchers and authorities have had increasing focus on
      leaching properties from waste incineration bottom ashes. Researchers have
      investigated processes such as those related to carbonation, weathering, metal
      complexation, and leaching control. Most of these investigations, however, have
      had a strong emphasis on lab experiments with little focus on full-scale bottom
      ash upgrading methods. The introduction of regulatory limit values restricting
      leaching from utilized bottom ashes, has created a need for a better
      understanding of how lab-scale experiences can be utilized in full-scale bottom
      ash upgrading facilities, and the possibilities for complying with the regulatory
      limit values. A range of Danish research and development projects have, during
      1997-2005, investigated important techniques for bottom ash upgrading. The
      primary focus has been placed on curing/aging, washing with and without
      additives, organic matter, sampling techniques, utilization options, and
      assessment tools. This paper provides an overview of these projects. The main
      results and experiences are discussed and evaluated with respect to bottom ash
      upgrading and utilization. Based on this discussion, development needs and
      potential management strategies are identified.

PMID- 17512720
TI  - Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM)
      guidelines for clinical use.
AB  - The aim of this article is to present updated guidelines for the use of serum,
      tissue and faecal markers in colorectal cancer (CRC). Lack of specificity and
      sensitivity preclude the use of all existing serum markers for the early
      detection of CRC. For patients with stage II or stage III CRC who may be
      candidates for either liver resection or systemic treatment should recurrence
      develop, CEA should be measured every 2-3 months for at least 3 years after
      diagnosis. Insufficient evidence exists to recommend routine use of tissue
      factors such as thymidylate synthase, microsatellite instability (MSI), p53, K
      ras and deleted in colon cancer (DCC) for either determining prognosis or
      predicting response to therapy in patients with CRC. Microsatellite instability,
      however, may be used as a pre-screen for patients with suspected hereditary non
      polyposis colorectal cancer. Faecal occult blood testing but not faecal DNA
      markers may be used to screen asymptomatic subjects 50 years or older for early
      CRC.

PMID- 17512721
TI  - Age of menopause among women who remain premenopausal following treatment for
      early breast cancer: long-term results from International Breast Cancer Study
      Group Trials V and VI.
AB  - BACKGROUND: The likelihood of premature menopause has not been thoroughly
      explored in women who remain premenopausal after adjuvant chemotherapy for breast
      cancer. METHODS: We used data from the International Breast Cancer Study Group
      (IBCSG) Trials V and VI. Trial V enrolled 1407 eligible premenopausal women
      randomised to no systemic therapy (No CT) or 1 cycle of perioperative CMF-based
      chemotherapy (PeCT) if node negative, and 6 cycles of CMF-based chemotherapy
      postoperatively (CMFx6) or 1 cycle perioperative CMF-based chemotherapy plus
      CMFx6 postoperatively (CMFx7) if node positive. From Trial VI (a 2x2 factorial
      designed study of 3 versus 6 initial cycles of CMF and a reintroduction of three
      additional courses of CMF), we included 375 women randomised to receive only six
      initial cycles of CMF (CMFx6). FINDINGS: We excluded women who reported no menses
      during 12-24 months after randomisation (N=934), hysterectomy (N=16) or bilateral
      oophorectomy (N=8), or missing menses data (N=57), creating a cohort of 767
      women; 540 women had been randomised to PeCT or no CT, 227 randomised to CMFx6 or
      7. A Cox proportional hazards model revealed that CMFx6 or 7 (HR=2.03, p<0.0001)
      and temporary amenorrhea (HR=1.96, p<0.0001) were associated with premature
      menopause. INTERPRETATION: Women who remain premenopausal after 6 or 7 cycles of
      CMF-based chemotherapy have a higher likelihood of going through menopause at an
      earlier age than women who received little or no chemotherapy. Temporary
      cessation of menses appears to be a marker for earlier onset of menopause. These
      findings may assist women and clinicians when making treatment and reproductive
      decisions after a diagnosis of breast cancer.

PMID- 17512722
TI  - The risk of developing cervical cancer in Mexican women is associated to CYP1A1
      MspI polymorphism.
AB  - The aim of the study was to evaluate the association of two CYP1A1 polymorphisms
      (Msp1 and exon 7) with cervical cancer in Mexican women considering their smoking
      habit. The polymorphisms were determined in 310 individuals (155 with cervical
      cancer and 155 healthy controls). Women with MspI T/C or C/C showed increased
      risk of developing cervical cancer (3.7- and 8.3-fold increase, respectively)
      compared to women with T/T genotype. When smoking habit was considered, the risk
      for non-smokers with T/C and C/C genotypes was similar (5.2 and 4.1,
      respectively), whereas smoking women with C/C genotype showed a 19.4-fold
      increase of cervical cancer. Number of child births, number of sexual partners
      and marital status were strong risk factors for developing cervical cancer in
      women with T/T genotype; however, in women with T/C genotype, only the number of
      child births and sexual partners had a significant influence. These results
      suggest an important role of the CYP1A1 MspI polymorphism in the risk of
      developing cervical cancer.

PMID- 17512723
TI  - RDH12, a retinol dehydrogenase causing Leber's congenital amaurosis, is also
      involved in steroid metabolism.
AB  - Three retinol dehydrogenases (RDHs) were tested for steroid converting abilities:
      human and murine RDH 12 and human RDH13. RDH12 is involved in retinal
      degeneration in Leber's congenital amaurosis (LCA). We show that murine Rdh12 and
      human RDH13 do not reveal activity towards the checked steroids, but that human
      type 12 RDH reduces dihydrotestosterone to androstanediol, and is thus also
      involved in steroid metabolism. Furthermore, we analyzed both expression and
      subcellular localization of these enzymes.

PMID- 17512724
TI  - Bacterial reduction of selenate to elemental selenium utilizing molasses as a
      carbon source.
AB  - Selecting an inexpensive and effective organic carbon source is the key to
      reducing the cost in selenium (Se) remediation. Five bacteria were screened based
      on their ability in using molasses as an organic carbon source to reduce selenate
      [Se(VI)] in drainage water. Efficiency of Se removal differed in the molasses
      added drainage water containing different bacteria, with an order of Enterobacter
      taylorae>Pantoea sp. SSS2>Klebsiella sp. WRS2>Citerobacter freundii>Shigella sp.
      DW2. By using E. taylorae, 97% of the added Se(VI) (1000 microg/L) was reduced to
      elemental Se [Se(0)] in an artificial drainage water during an 11-day experiment,
      and 93% of Se(VI) in a natural agricultural drainage water was reduced to Se(0)
      and organic Se during a 7-day experiment. E. taylorae also rapidly removed Se(VI)
      in agar-coated sand columns. During 45 days of the experiment, more than 92% of
      influent Se was removed from the drainage water with a molasses range of 0.01
      0.1%. This study reveals that molasses may be a cost-effective organic carbon
      source used by Se(VI)-reducing bacteria to remove Se from agricultural drainage
      water in field.

PMID- 17512725
TI  - Effects of different green manures on soil biological properties and maize yield.
AB  - The utilization of green manures as alternatives to reduce the use of mineral
      fertilizers is considered a good agricultural practice. However, the effect of
      each green manure on soil properties and crop yield depends upon its chemical
      composition. The main objective of this work was to study the effect of
      incorporating three green manures originating from residues of Trifolium
      pratense, L. (TP), Brassica napus, L. (BN), and the mixture of TP+BN at rates of
      5384 and 8973 kg C ha(-1), on soil biological properties (soil microbial biomass
      C, soil respiration and soil enzymatic activities), nutrition (leaf N, P and K
      concentration, pigments and soluble carbohydrate concentrations) and yield
      parameters of maize (Zea mays cv. Tundra) crop for four years on an Typic
      Xerofluvent located near Sevilla (Guadalquivir Valley, Andalusia, Spain). All
      green manures had a positive effect on the soil biological properties, plant
      nutrition an crop yield parameters, although at the end of the experimental
      period and at the high organic matter rate, the soil microbial biomass and
      dehydrogenase, urease, beta-glucosidase, phosphatase and arylsulfatase activities
      increased more significantly in the TP amended soils (79.2%, 92.1%, 93.9%, 99.3%,
      87.9% and 96%, respectively) respect to the control soil, followed by TP+BN
      amended soils (77.3%, 90.9%, 92.8%, 99.1%, 84.4% and 95.7%, respectively) and BN
      amended soils (76%, 90.1%, 91.7%, 99%, 83.2% and 95.2%, respectively). Since
      these soil enzymatic activities measured are responsible for important cycles
      such as C, N, P and S, an increase of leaf N, P an K contents and pigments and
      soluble carbohydrate contents were highest in TP amended soils, followed by TP+BN
      and BN treatments. The application of TP in soils at high doses increased the
      grain protein concentration, number of grains corncob(-1) and crop yield 44.6%,
      6.3% and 22.1%, respectively, compared with the control soil, followed by TP+BN
      treatment (41.7%, 5.7% and 20.8%, respectively) and BN treatment (39%, 5.3% and
      20%, respectively). The explanation of these results can be a consequence to the
      different chemical composition of the green manures applied to the soils and its
      mineralization, aspect controlled by the soil C/N ratio.

PMID- 17512726
TI  - Free radical scavenging activity of a novel antioxidative peptide purified from
      hydrolysate of bullfrog skin, Rana catesbeiana Shaw.
AB  - In the present study, a peptide having antioxidant properties was isolated from
      bullfrog skin protein, Rana catesbeiana Shaw. Bullfrog skin protein was
      hydrolyzed using alcalase, neutrase, pepsin, papain, alpha-chymotrypsin and
      trypsin. Antioxidant activities of respective hydrolysates were evaluated using
      lipid peroxidation inhibition assay and direct free radical scavenging activity
      by using electron spin resonance (ESR) spectrometer. Among hydrolysates, alcalase
      derived hydrolysate exhibited the highest antioxidant activities than those of
      other enzyme hydrolysates. In order to purity a peptide having potent antioxidant
      properties, alcalase hydrolysate was separated using consecutive chromatographic
      methods on a Hiprep 16/10 DEAE FF anion exchange column, Superdex Peptide 10/300
      GL gel filtration column and highan octadecylsilane (ODS) C18 reversed phase
      column. Finally, a potent antioxidative peptide was isolated and its sequence was
      identified to be LEELEEELEGCE (1487 Da) by Q-TOF ESI mass spectroscopy. This
      antioxidant peptide from bullfrog skin protein (APBSP) inhibited lipid
      peroxidation higher than that of alpha-tocopherol as positive control and
      efficiently quenched different sources of free radicals: DPPH radical
      (IC(50)=16.1 microM), hydroxyl radical (IC(50)=12.8 microM), superoxide radical
      (IC(50)=34.0 microM) and peroxyl radical (IC(50)=32.6 microM). Moreover, MTT
      assay showed that this peptide does not exert any cytotoxicity on human embryonic
      lung fibroblasts cell line (MRC-5).

PMID- 17512727
TI  - Potential density and basal area prediction equations for unthinned Eucalyptus
      hybrid plantations in the Gujarat state of India.
AB  - The aim of this paper is to present equation for estimating potential stand
      density and basal area projection model for unthinned pure even-aged plantations
      of Eucalyptus hybrid in Gujarat State of India. Relationships between quadratic
      mean diameter and stems ha(-1) were developed, which was used to establish the
      limiting density line. Eight different stand level models, belonging to the path
      invariant algebraic difference form of a non-linear growth function, were
      compared for projecting basal area. They can be used to predict future basal area
      as a function of stand variables like dominant height and stem number per hectare
      and are crucial for evaluating different silvicultural treatment options. The
      performance of the models was evaluated using different statistical criteria. The
      model proposed by Pienaar and Shiver performed best and hence is recommended for
      projecting the basal area in E. hybrid stands.

PMID- 17512728
TI  - Removal of heavy metals from contaminated sewage sludge using Aspergillus niger
      fermented raw liquid from pineapple wastes.
AB  - The environmental benefits derived from using citric acid in the removal of heavy
      metals from contaminated sewage sludge have made it promising as an extracting
      agent in the chemical extraction process. At present, citric acid is produced
      commercially by fermentation of sucrose using mutant strains of Aspergillus niger
      (A. niger), and chemical synthesis. In recent years, various carbohydrates and
      wastes (such as pineapple wastes) have been considered experimentally, to produce
      citric acid by A. niger. This study investigated the potential of using A. niger
      fermented raw liquid from pineapple wastes as a source of citric acid, in
      extracting chromium (Cr), copper (Cu), lead (Pb), nickel (Ni) and zinc (Zn) from
      anaerobically digested sewage sludge. Results of the study revealed that metal
      removal efficiencies varied with pH, forms of metals in sludge and contact time.
      At pH approaching 4, and contact time of 11 days, A. niger fermented liquid
      seemed to remove all Cr and Zn while removing 94% of Ni. Moreover, chemical
      speciation studies revealed that metals which are predominantly in the
      exchangeable and oxidizable phases seemed to exhibit ease of leachability (e.g.,
      Zn). The by-products of the process such as pineapple pulp and mycelium which are
      rich in protein, can still be used as animal feed. It can be said therefore that
      this novel process provides a sustainable way of managing contaminated sewage
      sludge.

PMID- 17512729
TI  - Antiproliferative and apoptosis inducing properties of pyrano[3,2-c]pyridones
      accessible by a one-step multicomponent synthesis.
AB  - 4-Arylpyrano-[3,2-c]-pyridones have been prepared by a one-step cyclocondensation
      of 4-hydroxy-1,6-dimethylpyridin-2(1H)-one with various substituted benzaldehydes
      and malononitrile. These heterocycles exhibit micromolar and submicromolar
      antiproliferative activity in HeLa and induce apoptosis in Jurkat cell lines.
      Structure-activity studies performed on a small library of these compounds show a
      pronounced cytotoxicity enhancing effect of the bromo substituent at the meta
      position of the C4 aromatic moiety.

PMID- 17512730
TI  - 4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives as non-peptidic selective
      delta-opioid agonists with potential anxiolytic/antidepressant properties. Part
      2.
AB  - Novel 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives have been prepared and
      their synthesis described herein. In vitro affinities for delta-, micro-, and
      kappa-opioid receptors are reported. Evaluation of some representative compounds
      from this series in the mouse neonatal ultrasonic vocalization test and the mouse
      tail suspension test revealed anxiolytic- and antidepressant-like effects,
      respectively, upon subcutaneous administration.

PMID- 17512731
TI  - Synthesis, bioactivity, theoretical and molecular docking study of 1-cyano-N
      substituted-cyclopropanecarboxamide as ketol-acid reductoisomerase inhibitor.
AB  - Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes the second common step
      in branched-chain amino acid biosynthesis. The catalyzed process consists of two
      stages, the first of which is an alkyl migration from one carbon atom to its
      neighbouring atom. The likely transition state is a cyclopropane derivative, thus
      a series of new cyclopropane derivatives, such as 1-cyano-N-substituted
      cyclopropanecarboxamide, were designed and synthesized. Their structures were
      verified by (1)H NMR, FTIR spectrum, MS and elemental analysis. The K(i) values
      of active compounds 2, 4b against rice KARI were 95.30+/-13.71, 207.9+/-21.99
      microM, respectively. The X-ray crystal structure of compound 4a was also
      determined. Auto-Dock was used to predict the binding mode of 4a. This was done
      by analyzing the interaction of the compounds 4a with the active sites of spinach
      KARI. This result was in accord with the result analyzed by the frontier
      molecular orbital theory.

PMID- 17512732
TI  - Incorporating new technologies into clinical practice without evidence of
      effectiveness in prospective studies: computer-aided detection (CAD) in breast
      screening reinforces the need for better initial evaluation.

PMID- 17512733
TI  - Part 1. Chemical and physical restraints in the management of mechanically
      ventilated patients in the ICU: contributing factors.
AB  - Chemical and physical restraints are frequently used in the intensive care unit
      (ICU) to control agitated patients and to prevent self-harm and unplanned
      extubations. Published work relating to the numerous issues of the care and
      treatment strategies for these patients remains conflicting and unclear.
      Literature regarding sedation and chemical restraint reveals a trend towards
      management with lighter sedation, use of sedation assessment tools and sedation
      protocols. It remains unclear which treatment is best for agitated and delirious
      patients, and the evidence on the effect of sedation is conflicting. A large
      portion of the literature on the use of physical restraint is from general
      hospital wards and residential homes, and not from the ICU environment. The
      purpose of this paper is to provide a summary of the existing literature on the
      use of physical and chemical restraints in the ICU setting. In Part 1 of this two
      part paper, the evidence on chemical and physical restraints is explored with
      specific focus on definition of terms, unplanned extubation, agitation, delirium
      and the impact of nurse-patient ratios in the ICU on these issues. Part 2 of the
      paper examines the evidence related to chemical and physical restraints from the
      perspective of the mechanically ventilated patient.

PMID- 17512734
TI  - Altered sensation over the lower leg following hamstring graft anterior cruciate
      ligament reconstruction with transverse femoral fixation.
AB  - Reports in the literature have previously identified altered sensation following
      hamstring graft ACL reconstruction in the distribution of the infragenicular
      branch of the saphenous nerve. We propose to show that altered sensation is more
      extensive, and can affect function. We aimed to identify the occurrence rate,
      site and extent of altered sensation following hamstring graft ACL
      reconstruction, and the consequences on subjective functional recovery. A
      retrospective study was performed. One hundred and seventeen consecutive patients
      undergoing hamstring graft ACL reconstruction using transverse femoral fixation
      over a 78 month period were invited to complete a postal questionnaire. The
      minimum follow-up was 13 months. The response rate was 73%. Altered sensation
      post-operatively was described by 60%, with 37% experiencing persisting symptoms
      at follow-up. Symptoms were present in the distribution of the lateral sural
      cutaneous nerve (33%), the saphenous nerve (26%), and the infragenicular branch
      of the saphenous nerve (12%). Restriction of activity was described by 33% of
      patients, and 28% felt their rehabilitation programme was affected because of
      these symptoms. Our results showed that altered sensation was common and
      extensive in our population. We are unaware of any other published reports of
      altered sensation over the lateral lower leg. We conclude that occult nerve
      injury to the lateral sural cutaneous nerve during preparation of the transverse
      femoral fixation may be responsible.

PMID- 17512735
TI  - Anterior cruciate ligament reconstruction with quadrupled semitendinosus tendon -
      minimum 6 year clinical and radiological follow-up.
AB  - This clinical study evaluates the minimum 6 year follow-up clinical, functional,
      radiological and isometric results after arthroscopic reconstruction of the
      anterior cruciate ligament (ACL) with quadrupled semitendinosus tendon autograft
      (femoral endobutton and tibial suture disc fixation). Seventy out of 85 operated
      patients (lost to follow-up 17%) with an average age of 34.3 years could be
      clinically examined at a mean follow-up time of 6 years and 4 months after
      surgery. Results revealed a high subjective satisfaction rate of 93%. The
      preoperative activity level could be maintained in 71% of the patients. The
      Lysholm score showed very good and good results in 85% with a mean of 83.6%.
      Normal or nearly normal results on the IKDC score were reported in 85% of the
      patients. The KT-1000 arthrometer stability testing showed a difference of less
      than 3 mm compared to the contralateral knee in 75% of the patients. Five
      patients (7%) had a graft failure during follow-up time. There were no or only
      mild degenerative changes at the radiographic evaluation in 85% of the patients.
      In 15% of the patients a femoral and in 40% a tibial tunnel widening of more than
      50% was observed, however without a relevance for the clinical and functional
      status. Midterm results obtained in this study after arthroscopic ACL
      reconstruction with the quadrupled semitendinosus tendon confirm the outcomes in
      the literature after shorter follow-up periods that provide very good and good
      subjective, functional and stability results in about 80-85% of the patients.
      This surgical technique can be recommended for the active patient with ACL
      deficiency. However, patients must be informed that activity level cannot always
      be maintained and a failure rate of 5-10% must be taken into account in the
      longer term when decision for surgery is made.

PMID- 17512736
TI  - Structural basis for the activity of the RSK-specific inhibitor, SL0101.
AB  - Inappropriate activity of p90 ribosomal S6 kinase (RSK) has been implicated in
      various human cancers as well as other pathologies. We previously reported the
      isolation, characterization, and synthesis of the natural product kaempferol 3-O
      (3'',4''-di-O-acetyl-alpha-l-rhamnopyranoside), termed SL0101 [Smith, J. A.;
      Poteet-Smith, C. E.; Xu, Y.; Errington, T. M.; Hecht, S. M.; Lannigan, D. A.
      Cancer Res., 2005, 65, 1027-1034: Xu, Y.-M; Smith, J. A.; Lannigan, D. A.; Hecht,
      S. M. Bioorg. Med. Chem., 2006, 14, 3974-3977: Maloney, D. J.; Hecht, S. M. Org.
      Lett., 2005, 7, 1097-1099]. SL0101 is a potent and specific inhibitor of RSK;
      therefore, we performed an analysis of the structural basis for the inhibitory
      activity of this lead compound. In in vitro kinase assays we found that acylation
      of the rhamnose moiety and the 4', 5, and 7-hydroxyl groups are responsible for
      maintaining a high affinity interaction of RSK with SL0101. It is likely that the
      hydroxyl groups facilitate RSK binding through their ability to form hydrogen
      bonds. To determine whether the SL0101 derivatives were specific for inhibition
      of RSK we analyzed their ability to preferentially inhibit the growth of the
      human breast cancer line, MCF-7, compared to the normal human breast line, MCF
      10A. We have previously validated this differential growth assay as a convenient
      readout for analyzing the specificity of RSK inhibitors [Smith, J. A.; Maloney,
      D. J.; Clark, D. E.; Xu, Y.-M.; Hecht, S. M.; Lannigan, D. A. Bioorg. Med. Chem.,
      2006, 14, 6034-6042]. We found that acylation of the rhamnose moiety was
      essential for maintaining the selectivity for RSK inhibition in intact cells.
      Further, the efficacy of SL0101 in intact cells is limited by cellular uptake as
      well as possible hydrolysis of the acetyl groups on the rhamnose moiety by
      ubiquitous intracellular esterases. These studies should facilitate the
      development of a RSK inhibitor, based on the SL0101 pharmacophore, as an anti
      cancer chemotherapeutic agent.

PMID- 17512737
TI  - Spectroscopic properties of pyrene-containing DNA mimics.
AB  - DNA mimics containing non-nucleosidic pyrene building blocks are described. The
      modified oligomers form stable hybrids, although a slight reduction in hybrid
      stability is observed in comparison to the unmodified DNA duplex. The nature of
      the interaction between the pyrene residues in single and double stranded
      oligomers is analyzed spectroscopically. Intra- and interstrand stacking
      interactions of pyrenes are monitored by UV-absorbance as well as fluorescence
      spectroscopy. Excimer formation is observed in both single and double strands. In
      general, intrastrand excimers show fluorescence emission at shorter wavelengths
      (approx. 5-10 nm) than excimers formed by interstrand interactions. The existence
      of two different forms of excimers (intra- vs. interstrand) is also revealed in
      temperature dependent UV-absorbance spectra.

PMID- 17512738
TI  - Synthesis of a novel 'smart' bifunctional chelating agent 1-(2-[beta,D
      galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10
      bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and its
      Gd(III) complex.
AB  - A new synthetic pathway to 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3
      [4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane
      (Gal-PA-DO3A-NH2) and 1-(2-[beta,D-galactopyranosyloxy]ethyl)-4,7,10
      tris(carboxymethyl)-1, 4,7,10-tetraazacyclododecane (Gal-DO3A) chelating agents
      was developed involving full hydroxyl- and carboxyl-group protection in
      precursors to product. Two sequences of cyclen-N-functionalisation were
      subsequently investigated, one successfully, towards synthesis of the novel
      'smart' bifunctional Gal-PA-DO3A-NH2 chelate. The longitudinal proton
      relaxivities of the neutral [Gd-(Gal-PA-DO3A-NH2)] and [Gd-(Gal-DO3A)] complexes
      were increased by 28% and 37% in the presence of beta-galactosidase,
      respectively.

PMID- 17512739
TI  - RNA as scaffold for pyrene excited complexes.
AB  - Synthesis and spectral properties of 1-ethynylpyrene base modified RNA are
      reported. The fluorophore attached to the 2-position of adenosine is directed
      into the easily accessible minor groove in RNA. Through an intermolecular
      interaction of the pyrene residues in twofold labelled RNA, single and double
      strands can be distinguished by their fluorescence maxima around 450 and 480 nm,
      respectively. This behaviour allows the kinetic investigation of RNA
      hybridisation and folding by fluorescence spectroscopy.

PMID- 17512740
TI  - Toward the development of chemoprevention agents. Part 1: Design, synthesis, and
      anti-inflammatory activities of a new class of 2,5-disubstituted
      dioxacycloalkanes.
AB  - A new class of 2,5-disubstituted-dioxacycloalkanes were designed and synthesized
      via stereoselective synthetic method as cancer chemoprevention agents. The anti
      inflammatory activities of these compounds were tested using the xylene-induced
      mouse ear edema model. Some of these compounds exhibited comparable or better
      anti-inflammatory activities than that of aspirin suggesting that they can be
      further developed as potential anti-inflammatory drug lead compounds. In
      addition, treatment of these anti-inflammatory agents did not prolong tail
      bleeding time in mice. The structure/activity relationships were also analyzed
      among these compounds.

PMID- 17512741
TI  - Cytotoxic dibromotyrosine-derived metabolites from the sponge Aplysina
      gerardogreeni.
AB  - The chemical study of the sponge Aplysina gerardogreeni collected at the Gulf of
      California has led to the isolation of four new dibromotyrosine-derived
      metabolites, aplysinones A-D, whose structures were determined by spectroscopic
      analysis and chemical methods. The new compounds and four semisynthetic analogues
      prepared in this study have shown cytotoxic activity against human tumor cell
      lines.

PMID- 17512742
TI  - Simultaneous presence of unsaturation and long alkyl chain at P'1 of Ilomastat
      confers selectivity for gelatinase A (MMP-2) over gelatinase B (MMP-9) inhibition
      as shown by molecular modelling studies.
AB  - Structural analogues of Ilomastat (Galardin), containing unsaturation(s) and
      chain extension carrying bulky phenyl group or alkyl moieties at P'1 were
      synthesized and purified by centrifugal partition chromatography. They were
      analyzed for their inhibitory capacity towards MMP-1, MMP-2, MMP-3, MMP-9 and MMP
      14, main endopeptidases involved in tumour progression. Presence of
      unsaturation(s) decreased the inhibitory potency of compounds but, in turn
      increased their selectivity for gelatinases. 2b and 2d derivatives with a phenyl
      group inhibited preferentially MMP-9 with IC50 equal to 45 and 38 nM,
      respectively, but also display activity against MMP-2 (IC50 equal to 280 and 120
      nM, respectively). Molecular docking computations confirmed affinity of these
      substances for both gelatinases. With aims to obtain a specific gelatinase A (MMP
      2) inhibitor, P'1 of Ilomastat was modified to carry one unsaturation coupled to
      an alkyl chain with pentylidene group. Docking studies indicated that MMP-2, but
      not MMP-9, could accommodate such substitution; indeed 2a proved to inhibit MMP-2
      (IC50=123 nM), while displaying no inhibitory capacity towards MMP-9.

PMID- 17512743
TI  - Optimizing the enzymatic synthesis of beta-D-galactopyranosyl-D-xyloses for their
      use in the evaluation of lactase activity in vivo.
AB  - Disaccharides 2-O-, 3-O-, and 4-O-beta-D-galactopyranosyl-D-xyloses (2, 3, and 1,
      respectively) were obtained by beta-galactosidase-catalyzed reactions for their
      use in the evaluation of intestinal lactase activity in vivo. Their
      administration to suckling rats followed by determination of the derived D-xylose
      in the urine and measurement of lactase activity in intestinal homogenates showed
      1 to be the most suitable disaccharide for a potential test of the deficiency of
      intestinal lactase. The synthesis of 1 was further studied by evaluating the
      effect of different variables on the yield and regioselectivity of the enzymatic
      galactosylation, and the purification process was optimized.

PMID- 17512744
TI  - Inhibition of colon cancer cell growth and antioxidant activity of bioactive
      compounds from Poncirus trifoliata (L.) Raf.
AB  - Recently several plant derived natural compounds have been screened for their
      anticancer activity in order to identify putative compounds with novel structures
      or mechanism of action. In the present study, fruits of Poncirus trifoliata were
      extracted with acetone and loaded onto silica gel column chromatography. The
      column was eluted with different solvents to obtain two bioactive compounds. The
      purity of compounds was analyzed by HPLC and their structures were identified by
      1H and 13C NMR experiments as beta-sitosterol and 2-hydroxy-1,2,3
      propanetricarboxylic acid 2-methyl ester (HPCME). beta-Sitosterol, HPCME, and
      trolox were tested for their antioxidant capacity by oxygen radical absorbance
      capacity (ORAC) measurement. Further, these compounds were tested for their
      inhibition of cancer cell proliferation and apoptosis using human colon cancer
      cell line (HT-29). These results were compared with the corresponding activity on
      non-cancerous (COS-1 fibroblast) cells. Cell proliferation and induction of
      apoptosis were determined by MTT assay and nuclear staining. The MTT assay
      indicated that both the compounds exhibited differential inhibition at various
      concentrations. Significant arrest of cell growth was observed with beta
      sitosterol even at low concentration such as 0.63 microM in 48 h and none of the
      compounds exerted any apparent cytostatic effects on the non-cancerous COS-1
      fibroblast cells. Growth inhibition assay suggested the potential use of
      bioactive compounds as cancer chemopreventive and therapeutic agents. This is the
      first report on HPCME isolation and identification from Rutaceae family and beta
      sitosterol from P. trifoliata.

PMID- 17512745
TI  - Meiotic nucleolar cycle and chromatoid body formation during the rat (Rattus
      novergicus) and mouse (Mus musculus) spermiogenesis.
AB  - The aims of the present study were to follow the nucleolar cycle in
      spermiogenesis of the laboratory rodents Rattus novergicus and Mus musculus, to
      verify the relationship between the nucleolar component and chromatoid body (CB)
      formation and to investigate the function of this cytoplasmic supramolecular
      structure in spermatogenic haploid cells. Histological sections of adult
      seminiferous tubules were analyzed cytochemically by light microscopy and
      ultrastructural procedures by transmission electron microscopy. The results
      reveal that in early spermatids, the CB was visualized in association with the
      Golgi cisterns indicating that this structure may participate in the acrosome
      formation process. In late spermatids, the CB was observed near the axonema, a
      fact suggesting that this structure may support the formation of the spermatozoon
      tail. In conclusion, our data showed that there is disintegration of spermatid
      nucleoli at the beginning of spermatogenesis and a fraction of this nucleolar
      material migrates to the cytoplasm, where a specific structure is formed, known
      as the "chromatoid body", which, apparently, participates in some parts of the
      rodent spermiogenesis process.

PMID- 17512746
TI  - Automatic registration of serial sections of mouse lymph node by using Image-Reg.
AB  - The first step towards the three-dimensional (3D) reconstruction of histological
      structures from serial sectioned tissue blocks is the proper alignment of
      microscope image sequences. We have accomplished an automatic rigid registration
      program, named Image-Reg, to align serial sections from mouse lymph node and
      Peyer's patch. Our approach is based on the calculation of the pixel-correlation
      of objects in adjacent images. The registration process is mainly divided into
      two steps. Once the foreground images have been segmented from the original
      images, the first step (primary alignment) is performed on the binary images of
      segmented objects; this process includes rotation by using the moments and
      translation through the X, Y axes by using the centroid. In the second step, the
      matching error of two binary images is calculated and the registration results
      are refined through multi-scale iterations. In order to test the registration
      performance, Image-Reg has been applied to an image and its transformed (rotated)
      version and subsequently to an image sequence of three serial sections of mouse
      lymph node. In addition, to compare our algorithm with other registration
      methods, three other approaches, viz. manual registration with Reconstruct, semi
      automatic landmark registration with Image-Pro Plus and the automatic phase
      correlation method with Image-Pro Plus, have also been applied to these three
      sections. The performance of our program has been also tested on other two-image
      data sets. These include: (a) two light microscopic images acquired by the
      automatic microscope (stitched with other software); (b) two images fluorescent
      images acquired by confocal microscopy (tiled with other software). Our proposed
      approach provides a fast and accurate linear alignment of serial image sequences
      for the 3D reconstruction of tissues and organs.

PMID- 17512747
TI  - Standardisation of a 229Th solution.
AB  - The use of (229)Th as tracer has become generalised for determination of
      naturally occurring alpha-emitting thorium isotopes. This paper describes two
      procedures that allow standardising (229)Th solutions of the order of Bq/g
      without the need of radiochemical separation of its daughters.

PMID- 17512748
TI  - Differential effects on forelimb grasping behavior induced by fetal dopaminergic
      grafts in hemiparkinsonian rats.
AB  - Skilled forelimb movements depend on an intact dopaminergic (DA)
      neurotransmission and are substantially impaired in the unilateral rat model of
      Parkinson's disease. It has remained unclear, however, to what extent reaching
      and grasping movements can be influenced by intrastriatal transplantation of
      fetal DA neurons. Here an extensive behavioral assessment of skilled forelimb
      movement patterns in hemiparkinsonian and DA-grafted rats was carried out. Good
      DA graft survival was accompanied by a compensation of drug-induced rotational
      asymmetries. Interestingly, skilled forelimb use was significantly improved in
      transplanted animals as compared to lesion-only animals in the staircase test.
      Qualitative analysis of single forelimb reaching movement components revealed
      dissociable patterns of graft effects: while some movement components in grafted
      animals improved, others remained unchanged or even deteriorated. These findings
      provide novel insights into the complex interactions of graft-derived restoration
      of DA neurotransmission and skilled forelimb behavior.

PMID- 17512749
TI  - Biological abnormalities of peripheral A(2A) receptors in a large representation
      of polyglutamine disorders and Huntington's disease stages.
AB  - Huntington's disease is one of a group of hereditary neurodegenerative diseases
      characterized by a glutamine expansion (polyQ) in proteins which are expressed in
      various cell populations. In agreement with this widespread distribution, we have
      previously shown that A(2A) receptor signaling is affected in mouse brain as well
      as in peripheral blood cells from a small cohort of HD patients. Here we analyzed
      a total of 252 subjects, including 126 HD gene-positive individuals, from
      different clinical sites. Consistent with our previous data we show that A(2A)
      receptor B(max) values are robustly increased at all HD stages as well as in 32
      pre-symptomatic subjects. We report that the same abnormality is present also in
      other polyQ but not in non-polyQ inherited neurological disorders. Finally, we
      demonstrate that the same peripheral cells exhibit an altered membrane fluidity,
      a finding that may explain the observed change in receptor density. We argue that
      the observed alteration in lymphocytes reflects the presence of the mutant
      protein, and we suggest that the measure of the A(2A) receptor binding activity
      might be of potential interest for a peripheral assessment of chemicals capable
      of interfering with the immediate toxic effects of the mutation.

PMID- 17512750
TI  - NGF topical application in patients with corneal ulcer does not generate
      circulating NGF antibodies.
AB  - Nerve growth factor (NGF) is the prototype of the neurotrophin family and
      promotes the survival of specific populations of neurons, stimulates their
      morphological differentiation and regulates neuronal gene expression. Since its
      discovery, NGF attracted clinicians for its potential application in the
      treatment of neurological disorders. Recent studies demonstrated murine NGF eye
      drops may be successfully used to treat neurotrophic keratopathy. Neurotrophic
      keratopathy is a degenerative corneal disease caused by an impairment of the
      trigeminal nerve, which leads to corneal epithelial defect, ulcer, and
      perforation. NGF topical application induced complete ulcer healing and a
      recovery of the corneal sensitivity. The intent of this study is to address the
      question if murine NGF topical treatment stimulates the production of circulating
      anti-NGF antibodies. We evaluated patients with neurotrophic keratopathy who
      underwent topical therapy with NGF eye drops for possible ocular or systemic
      adverse effects in the course of 16-72 months follow up. None of the patients
      suffered any adverse reaction, except for mild and transient conjunctival
      hyperaemia and photophobia. Moreover, none of the treated patients developed
      circulating antibodies to NGF.

PMID- 17512751
TI  - A collision cross-section database of singly-charged peptide ions.
AB  - A database of ion-neutral collision cross-sections for singly-charged peptide
      ions is presented. The peptides included in the database were generated by
      enzymatic digestion of known proteins using three different enzymes, resulting in
      peptides that differ in terms of amino acid composition as well as N-terminal and
      C-terminal residues. The ion-neutral collision cross-sections were measured using
      ion mobility (IM) spectrometry that is directly coupled to a time-of-flight (TOF)
      mass spectrometer. The ions were formed by a matrix-assisted laser desorption
      ionization (MALDI) ion source operated at pressures (He bath gas) of 2 to 3 torr.
      The majority (63%) of the peptide ion collision cross-sections correlate well
      with structures that are best described as charge-solvated globules, but a
      significant number of the peptide ions exhibit collision cross-sections that are
      significantly larger or smaller than the average, globular mobility-mass
      correlation. Of the peptide ions having larger than average collision cross
      sections, approximately 71% are derived from trypsin digestion (C-terminal Arg or
      Lys residues) and most of the peptide ions that have smaller (than globular)
      collision cross-sections are derived from pepsin digestion (90%).

PMID- 17512753
TI  - Enhanced protease cleavage efficiency on the glucagon-fused interleukin-2 by the
      addition of synthetic oligopeptides.
AB  - Human interleukin-2 (hIL-2) was produced as a recombinant fusion protein (G3.IL
      2/HF) consisting of three tandem-arranged human glucagon molecules (G3) and hIL
      2. For the recovery of hIL-2, a factor Xa (FXa) cleavage sequence was introduced
      next to the N-terminus of hIL-2. Cleavage efficiency on this recombinant protein
      construct was very low because its recognition sequence was sterically hindered
      within the G3.IL-2/HF molecule and hence FXa access to the cleavage site was
      insufficient. We therefore introduced various synthetic oligopeptides upstream
      from the FXa cleavage site as a means to change substrate conformation and
      thereby increase cleavage efficiency. Among these oligopeptides, acidic or
      nucleophilic constructs were the most effective for the FXa-mediated cleavage of
      the fusion protein. In addition, insertion of various oligopeptides into the
      G3.IL-2/HF molecule varied the solubility of each construct depending on their
      physical properties. Consequently, the G3.IL-2/DF construct showed the highest
      final hIL-2 yields via FXa-mediated removal of the fusion partner. Lastly, we
      confirmed that cleavage efficiency was greatly increased but native hIL-2 was
      cleaved internally by non-specific cleavage when the acidic oligopeptide D4
      (DDDD) was introduced upstream of the EK cleavage site within G3.IL-2/HE
      molecule. The G3.IL-2/HE molecule was shown to be an inefficient substrate to EK
      in a previous report (Biotechnol. Bioprocess Eng. (2000) 5, 13-16).

PMID- 17512752
TI  - Ion mobility spectrometry-mass spectrometry performance using electrodynamic ion
      funnels and elevated drift gas pressures.
AB  - The ability of ion mobility spectrometry coupled with mass spectrometry (IMS-MS)
      to characterize biological mixtures has been illustrated over the past eight
      years. However, the challenges posed by the extreme complexity of many biological
      samples have demonstrated the need for higher resolution IMS-MS measurements. We
      have developed a higher resolution ESI-IMS-TOF MS by utilizing high-pressure
      electrodynamic ion funnels at both ends of the IMS drift cell and operating the
      drift cell at an elevated pressure compared with that conventionally used. The
      ESI-IMS-TOF MS instrument consists of an ESI source, an hourglass ion funnel used
      for ion accumulation/injection into an 88 cm drift cell, followed by a 10 cm ion
      funnel and a commercial orthogonal time-of-flight mass spectrometer providing
      high mass measurement accuracy. It was found that the rear ion funnel could be
      effectively operated as an extension of the drift cell when the DC fields were
      matched, providing an effective drift region of 98 cm. The resolution of the
      instrument was evaluated at pressures ranging from 4 to 12 torr and ion mobility
      drift voltages of 16 V/cm (4 torr) to 43 V/cm (12 torr). An increase in
      resolution from 55 to 80 was observed from 4 to 12 torr nitrogen drift gas with
      no significant loss in sensitivity. The choice of drift gas was also shown to
      influence the degree of ion heating and relative trapping efficiency within the
      ion funnel.

PMID- 17512754
TI  - Gender disparities in managed care: it's time for action.

PMID- 17512755
TI  - fMRI visualization of transient activations in the rat olfactory bulb using short
      odor stimulations.
AB  - Odor-evoked activity in the olfactory bulb displays both spatial and temporal
      organization. The difficulty when assessing spatio-temporal dynamics of olfactory
      representation is to find a method that reconciles the appropriate resolution for
      both dimensions. Imaging methods based on optical recordings can reach high
      temporal and spatial resolution but are limited to the observation of the
      accessible dorsal surface. Functional magnetic resonance imaging (fMRI) may be
      useful to overcome this limitation as it allows recording from the whole brain.
      In this study, we combined ultra fast imaging sequence and short stimulus
      duration to improve temporal resolution of odor-evoked BOLD responses. Short odor
      stimulations evoked high amplitude BOLD responses and patterns of activation were
      similar to those obtained in previous studies using longer stimulations.
      Moreover, short odor exposures prevented habituation processes. Analysis of the
      BOLD signal time course in the different areas of activation revealed that
      odorant response maps are not static entities but rather are temporally dynamic
      as reported by recent studies using optical imaging. These data demonstrated that
      fMRI is a non-invasive method which could represent a powerful tool to study not
      only the spatial dimension of odor representation but also the temporal dimension
      of information processing.

PMID- 17512756
TI  - 3D pattern of brain abnormalities in Williams syndrome visualized using tensor
      based morphometry.
AB  - Williams syndrome (WS) is a neurodevelopmental disorder associated with deletion
      of approximately 20 contiguous genes in chromosome band 7q11.23. Individuals with
      WS exhibit mild to moderate mental retardation, but are relatively more
      proficient in specific language and musical abilities. We used tensor-based
      morphometry (TBM) to visualize the complex pattern of gray/white matter
      reductions in WS, based on fluid registration of structural brain images.
      METHODS: 3D T1-weighted brain MRIs of 41 WS subjects (age [mean+/-SD]: 29.2+/-9.2
      years; 23F/18M) and 39 age-matched healthy controls (age: 27.5+/-7.4 years;
      23F/16M) were fluidly registered to a minimum deformation target. Fine-scale
      volumetric differences were mapped between diagnostic groups. Local regions were
      identified where regional structure volumes were associated with diagnosis, and
      with intelligence quotient (IQ) scores. Brain asymmetry was also mapped and
      compared between diagnostic groups. RESULTS: WS subjects exhibited widely
      distributed brain volume reductions (approximately 10-15% reduction; P<0.0002,
      permutation test). After adjusting for total brain volume, the frontal lobes,
      anterior cingulate, superior temporal gyrus, amygdala, fusiform gyrus and
      cerebellum were found to be relatively preserved in WS, but parietal and
      occipital lobes, thalamus and basal ganglia, and midbrain were disproportionally
      decreased in volume (P<0.0002). These regional volumes also correlated positively
      with performance IQ in adult WS subjects (age > or = 30 years, P = 0.038).
      CONCLUSION: TBM facilitates 3D visualization of brain volume reductions in WS.
      Reduced parietal/occipital volumes may be associated with visuospatial deficits
      in WS. By contrast, frontal lobes, amygdala, and cingulate gyrus are relatively
      preserved or even enlarged, consistent with unusual affect regulation and
      language production in WS.

PMID- 17512757
TI  - Brain imaging of neuropathic pain.
AB  - Many studies have focused on defining the network of brain structures involved in
      normal physiological pain. The different dimensions of pain perception (i.e.,
      sensory discriminative, affective/emotional, cognitive/evaluative) have been
      shown to depend on different areas of the brain. In contrast, much less is known
      about the neural basis of pathological chronic pain. In particular, it is unclear
      whether such pain results from changes to the physiological "pain matrix". We
      review here studies on changes in brain activity associated with neuropathic pain
      syndromes-a specific category of chronic pain associated with peripheral or
      central neurological lesions. Patients may report combinations of spontaneous
      pain and allodynia/hyperalgesia-abnormal pain evoked by stimuli that normally
      induce no/little sensation of pain. Modern neuroimaging methods (positron
      emission tomography (PET) and functional MRI (fMRI)) have been used to determine
      whether different neuropathic pain symptoms involve similar brain structures and
      whether these structures are related to the physiological "pain matrix". PET
      studies have suggested that spontaneous neuropathic pain is associated
      principally with changes in thalamic activity and the medial pain system, which
      is preferentially involved in the emotional dimension of pain. Both PET and fMRI
      have been used to investigate the basis of allodynia. The results obtained have
      been very variable, probably reflecting the heterogeneity of patients in terms of
      etiology, lesion topography, symptoms and stimulation procedures. Overall, these
      studies indicated that acute physiological pain and neuropathic pain have
      distinct although overlapping brain activation pattern, but that there is no
      unique "pain matrix" or "allodynia network".

PMID- 17512758
TI  - The relative performance of indel-coding methods in simulations.
AB  - We used simulations to compare the performance of 10 approaches that have been
      used for treating unambiguously aligned gaps in phylogenetic analyses. We
      examined how these approaches perform under the ideal conditions of correct
      alignments, as well as how robust they are to errors caused by use of inferred
      alignments. Our results indicate that 5th-state coding dramatically outperformed
      all other coding methods, which in turn all outperformed treating gaps as missing
      data or excluding gapped positions. Simple indel coding (SIC) and modified
      complex indel coding (MCIC) performed about the same, and generally outperformed
      the other indel-coding methods. The high performance of 5th-state coding was
      largely found to be a weighting artifact. We suggest that MCIC-coded gap
      characters be scored for all unambiguously aligned gaps in parsimony-based
      molecular phylogenetic analyses. When the number of terminals sampled precludes
      the use of MCIC, SIC may be used as an effective substitute.

PMID- 17512759
TI  - Calibration of a molecular clock in tits (Paridae)--do nucleotide substitution
      rates of mitochondrial genes deviate from the 2% rule?
AB  - The ongoing debate on the reliability of avian molecular clocks is actually based
      on only a small number of calibrations carried out under different assumptions
      with respect to the choice and constraints of calibration points or to the use of
      substitution models. In this study, we provide substitution rate estimates for
      two mitochondrial genes, cytochrome b and the control region, and age estimates
      for lineage splits within four subgenera of tits (Paridae: Parus, Cyanistes,
      Poecile and Periparus). Overall sequence divergence between cytochrome b lineages
      covers a range of 0.4-1.8% per million years and is thus consistent with the
      frequently adopted approximation for a sequence divergence between avian lineages
      of 1.6-2% per my. Overall rate variation is high and encompasses the 2% value in
      a 95% CI for model corrected data. Mean rate estimates for cytochrome b range
      between 1.9 and 8.9 x 10(-3) substitutions per site per lineage. Local rates
      differ significantly between taxonomic levels with lowest estimates for haplotype
      lineages. At the population/subspecies level mean sequence divergence between
      lineages matches the 2% rule best for most cytochrome b datasets (1.5-1.9% per
      my) with maximum estimates for small isolated populations like those of the
      Canarian P. teneriffae complex (up to 3.9% per my). Overall rate estimates for
      the control region range at similar values like those for cytochrome b (2.7-8.8 x
      10(-3), 0.5-1.8% per my), however, within some subgenera mean rates are higher
      than those for cytochrome b for uncorrected sequence data. The lowest rates for
      both genes were calculated for coal tits of subgenus Periparus (0.04-0.6% per
      my). Model-corrected sequence data tend to result in higher rate estimates than
      uncorrected data. Increase of the gamma shape parameter goes along with a
      significant decrease of rate and partly age estimates, too. Divergence times for
      earliest deep splits within tit subgenera Periparus and Parus were dated to the
      mid Miocene at 10-14my bp. Most recent splits between east and west Palearctic
      taxa of blue, willow and great tits were dated to the Pliocene/Pleistocene
      boundary with the earliest estimates based on model-corrected trees. Relaxation
      of the Messinian calibration point leads to more recent divergence times for
      North African coal and blue tit populations during the mid Pliocene. Despite a
      relatively broad age constraint for the split between Nearctic and Palearctic
      Poecile due to the Pliocene re-opening of the Bering Strait, the split between
      chickadees and willow tits is dated considerably earlier than in former studies
      to the upper bound of the age constraint at 7.4 my BP.

PMID- 17512760
TI  - A novel approach for the determination of contractile and calcium responses of
      the basilar artery employing real-time confocal laser microscopy.
AB  - INTRODUCTION: Intracellular calcium concentration ([Ca(2+)](i)) modifications in
      endothelial and smooth muscle cells represent a key element in the pathogenesis
      of cerebral artery vasospasm. Therefore, the present study documented potential
      application of confocal laser microscopy in the determination of contractile and
      [Ca(2+)](i) responses in basilar artery. METHODS: Experiments were performed on
      the rat isolated basilar artery. Changes in [Ca(2+)](i) were determined by
      ratiometry involving Fluo-4/AM and Fura Red/AM. Contractile function was
      calculated from the change in fluorescent area by Fluo-4/AM. RESULTS: KCl (50 mM)
      elicited an increase in [Ca(2+)](i) and contraction in basilar artery; moreover,
      nearly well maintained responses were evident for at least 120 min following the
      first application. 10 microM 5-hydroxytryptamine (5-HT), 10 microM alpha,beta
      methyleneadenosine 5'-triphosphate (alpha,beta-meATP) and 10 nM vasopressin (VP)
      also induced increases in [Ca(2+)](i) and contraction dose-dependently.
      Additionally, 10 microM acetylcholine elicited a transient [Ca(2+)](i) decrease
      and sustained relaxation. In individual cells, rhythmical changes in [Ca(2+)](i)
      were observed after 10 microM 5-HT. VP (10 nM) evoked modest Ca(2+) oscillation
      in individual cells; however, Ca(2+) oscillation was not detectable with 10
      microM alpha,beta-meATP. DISCUSSION: These results indicate that this method
      offers reproducibility and quantifiable effects. Imaging technology may therefore
      be applied to the estimation of [Ca(2+)](i) responses at the tissue level as well
      as at the level of the individual cell. Thus, confocal laser microscopy is a
      suitable tool for estimation of small artery function.

PMID- 17512761
TI  - Zinc-finger transcription factor snail accelerates survival, migration and
      expression of matrix metalloproteinase-2 in human bone mesenchymal stem cells.
AB  - Although bone mesenchymal stem cells (BMSC) hold promise in gene therapy and
      tissue engineering, the inefficient migration and the low capability of
      subsequent survival of BMSC have largely restrained progress in these studies.
      Characteristics shared between stem cells and tumorigenic cells prompted us to
      investigate whether mechanisms of tumor progression contribute to stem cell
      migration. The transcription factor Snail which functions in epithelial
      mesenchymal transitions (EMT) is responsible for the acquisition of motile and
      invasive properties of tumor cells. It is not yet known whether Snail acts in the
      mechanisms of stem cell migration. Here it is shown that ectopic Snail expression
      increased the migration of BMSC in vitro by a mechanism dependent on the
      phosphoinositide 3-kinase (PI-3K) signaling pathway. Snail expression may
      contribute to the constitutive activation of signaling pathways of PI-3K and MAPK
      and the related MMP-2 secretion in BMSC. Furthermore, the stem cells expressing
      Snail were protected from the apoptosis triggered by serum deprivation. These
      results suggested the possibility for us to optimize the migration of BMSC toward
      infarcted tissues and their subsequent survival in the local microenvironment, by
      investigating mechanisms associated with the acquisition of invasiveness by tumor
      cells.

PMID- 17512762
TI  - The effect of substrate and adsorbed proteins on adhesion, growth and shape of
      CaCo-2 cells.
AB  - Extracellular matrix (ECM) proteins play a critical role in many cellular
      functions, from spreading, migration and proliferation to apoptosis. This role
      can be altered when proteins of the native ECM are adsorbed to different
      substrates which cause structural modifications that can influence their
      biological function. The effects on CaCo-2 cells of laminin-1, fibronectin,
      collagen-1 and ECM gel adsorbed to glass and to tissue culture polystyrene (PS)
      were compared in terms of adhesion, proliferation, shapes and spreading of cells
      in culture. Significant differences between glass and PS surfaces were observed
      for proliferation and cell shape. Protein surfaces prepared on PS substrates had,
      in most cases, more pronounced effects on cells than uncoated PS, especially if
      coated by collagen-1. Adsorbed ECM gel was the most adhesive for cells, but its
      effect on cell proliferation was not notably different from the controls (glass
      or PS). These findings indicate that the choice of the substrate can have a
      significant effect on experimental results and should be taken into consideration
      when comparing results obtained on different surfaces.

PMID- 17512763
TI  - Major groin complications following the use of synthetic grafts.
AB  - BACKGROUND: The ideal results of vascular reconstructive surgery include an
      uncomplicated operation, symptomatic relief, prompt wound healing, rapid return
      to pre-operative functional status without long term functional consequences.
      Long term complications are often not emphasized. This study describes false
      femoral aneurysms (FFA) and infection following use of synthetic graft in the
      groin. METHODS: All patients under the care of one surgeon, undergoing synthetic
      graft insertion involving the groin between January 1988 and December 2005 were
      included. RESULTS: Some 489 patients were included (745 at risk groins). A total
      of 34 patients developed either FFA or infection, involving 39 groins (5.2%).
      There were 18 FFA, presenting a median of four years after the original
      operation. FFA was more common following aortofemoral bypass grafts than
      femorofemoral or femorodistal bypasses (P=0.0084). Repair with interposition
      grafting was carried out in 17 cases. There was one death postoperatively. The
      remainder remained satisfactory at a median follow up of 60 months. Median time
      from original operation to 21 groin infections presenting was 12 months.
      Infection was commonest after femorofemoral cross over grafts P=0.023. Four major
      amputations were carried out. Debridement and sartorius transposition was useful
      in about half of the cases treated. CONCLUSION: Serious groin complications occur
      in about 5% of cases following use of a synthetic graft. This can result in
      significant morbidity long after the original operation has been carried out.
      Patients need to be made aware of this when obtaining informed consent.

PMID- 17512764
TI  - Highly characteristic and individual specific telomere length patterns in cattle.
AB  - A combined primed in situ labelling (PRINS)/4',6-diamino-2-phenylindole
      (DAPI)/propidium iodide (PI)-fluorescence-banding method was used to characterise
      telomeres, identify their specific chromosomes and visualise neighbouring
      heterochromatin in 25 artificial insemination (AI) bulls. A highly heterogeneous
      telomere length pattern was found in cattle. Each bull possessed his own
      characteristic, specific telomere length pattern.

PMID- 17512765
TI  - Selected parameters in urine as indicators of milk production in lactating sows:
      a pilot study.
AB  - Although insufficient milk production in lactating sows may cause tremendous
      economic losses, reliable methods for estimating milk production in sows under
      field conditions are not available. This study aimed to investigate whether urine
      parameters could be used to predict milk production in sows. The milk production
      of 18 sows was determined during early and mid-lactation. Morning (a.m.) and
      afternoon (p.m.) urinary levels of potassium (K), sodium (Na), calcium (Ca),
      magnesium (Mg), lactose and creatinine were analysed. The absolute
      concentrations, the ratios relative to creatinine, and the fractional excretions
      of all elements in urine were not significantly associated with milk production.
      The p.m./a.m. ratios of K, Na and Ca concentrations in urine (K(R), Na(R), and
      Ca(R)) were significant predictors for milk production, but only during mid
      lactation. The total variation in milk production (r(2) value) explained by K(R),
      Na(R), Ca(R) amounted to 72%, 55%, 42%, respectively. Analysis of minerals and
      especially K in the a.m. and p.m. urine of sows during mid-lactation provided an
      acceptable indication of milk production. Further research is necessary to
      investigate whether the present results can be used to estimate milk production
      in hypogalactic sows under field conditions.

PMID- 17512766
TI  - Spirocerca lupi infection in the dog: a review.
AB  - Spirocercosis is a disease occurring predominantly in Canidae, caused by the
      nematode Spirocerca lupi. Typical clinical signs are regurgitation, vomiting and
      dyspnoea. The life-cycle involves an intermediate (coprophagous beetle) and a
      variety of paratenic hosts. Larvae follow a specific migratory route, penetrating
      the gastric mucosa of the host, migrating along arteries, maturing in the
      thoracic aorta before eventually moving to the caudal oesophagus. Here the worm
      lives in nodules and passes larvated eggs which can be detected using zinc
      sulphate faecal flotation. Histologically, the mature oesophageal nodule is
      composed mostly of actively dividing fibroblasts. Spirocerca lupi-associated
      oesophageal sarcomas may occur and damage to the aorta results in aneurysms. A
      pathognomonic lesion for spirocercosis is spondylitis of the thoracic vertebrae.
      Primary radiological lesions include an oesophageal mass, usually in the terminal
      oesophagus, spondylitis, and undulation of the aortic border. Contrast
      radiography and computed tomography are helpful additional emerging modalities.
      Oesophageal endoscopy has a greater diagnostic sensitivity than radiography.
      Endoscopic biopsies are not sensitive for detecting neoplastic transformation.
      Doramectin is the current drug of choice, effectively killing adult worms and
      decreasing egg shedding. Early diagnosis of infection is still a challenge and to
      date no ideal regimen for prophylaxis has been published.

PMID- 17512767
TI  - Healthy herpetology: the role of the veterinarian in reptile prophylaxis.

PMID- 17512768
TI  - The seminal vesicle synthesizes steroids in the round goby Neogobius
      melanostomus.
AB  - In this study, we examine the possible contribution of the seminal vesicles of
      the male round goby to the production of putative steroidal pheromones. A
      previous study showed that the testes of the round goby are rich in steroid
      producing Leydig-like cells; and when incubated in vitro, convert tritiated
      androstenedione to at least six other steroids, including one not previously
      identified in fish--namely 3alpha-hydroxy-5beta-androstane-11,17-dione (11-oxo
      etiocholanolone, 11-oxo-ETIO). The seminal vesicles of reproductively mature
      males were examined by conventional histology, transmission electron microscopy
      and immunocytochemistry (utilizing an antibody against 3beta-hydroxysteroid
      dehydrogenase--a key enzyme in vertebrate steroid synthesis). All three
      procedures identified Leydig cells in the proximal and medial regions of the
      seminal vesicles. In vitro incubation of seminal vesicles with tritiated
      androstenedione demonstrated biosynthesis of 11-oxo-androstenedione, 11-oxo
      testosterone (more commonly known as 11-ketotestosterone) and 11 oxo-ETIO. These
      data indicate that the seminal vesicles, as well as the testes are involved in
      the synthesis of steroidal compounds that may function as pheromones.

PMID- 17512769
TI  - Cloning, expression and investigation for polymorphisms of canine peroxisome
      proliferator-activated receptors.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors implicated in lipid metabolism. In this study, the full
      length cDNA of canine PPARbeta and gamma were sequenced, and expression of PPARs
      was evaluated in normal tissues and primary cultures of adipocytes in dogs,
      followed by investigations for polymorphisms of canine PPARgamma. Comparison of
      the deduced amino acid sequences of canine PPARbeta and gamma cDNA with that of
      human PPARbeta and gamma cDNA revealed 95.9% and 98.2% identity, respectively.
      PPARbeta expression was ubiquitous and high PPARgamma expression was detected in
      the subcutaneous and omental adipose tissues, spleen and large intestine. Canine
      PPARgamma mRNA expression in cultured adipocytes began to increase from 4 days
      after induction of differentiation, and increased nearly ninefold within 10 days
      after induction of differentiation. Although expression level of PPARalpha was
      low in the cultured adipocytes, it slightly increased within 10 days. In
      contrast, expression of PPARbeta showed only small variations during adipocyte
      differentiation, though expression levels were relatively high. These results
      suggest that PPARgamma may play an important role in adipocyte differentiation in
      dogs. Investigations for polymorphisms of PPARgamma revealed a silent
      polymorphism, C1362T, in 3 of 92 dogs.

PMID- 17512770
TI  - Growth hormone response to low-dose apomorphine in restless legs syndrome.
AB  - INTRODUCTION: Low-dose apomorphine challenge has been shown to cause a rise in
      growth hormone (GH) in patients with Parkinson's disease (PD). This was
      interpreted as an increased postsynaptic sensitivity of hypothalamic dopamine
      receptors in the course of a generalized degeneration of dopaminergic neurons.
      The dopaminergic system in the restless legs syndrome (RLS) has been assumed to
      play a role in its pathophysiology. It is therefore the aim of this study to
      determine whether the GH response to subcutaneously applied low-dose apomorphine
      is generally altered in patients with RLS as compared to healthy controls.
      PATIENTS AND METHODS: We examined 40 patients with idiopathic RLS as well as 20
      age- and sex-matched healthy control subjects by means of the low-dose
      apomorphine test. GH was analyzed at baseline, as well as 45 and 60 min after
      subcutaneous low-dose apomorphine injection in the morning. RESULTS: Forty RLS
      patients (58.3+/-11.9 years, 32 females) with a mean RLS severity scale score of
      23.9+/-6.6 (range 10-37) were examined. GH was not significantly increased 45 and
      60 min after injection (p=0.397) (2.44+/-2.35 ng/ml at baseline versus 2.71+/
      2.29 ng/ml after 45 min and 2.18+/-1.83 ng/ml after 60 min). The results were
      independent of pre-treatment with levodopa. Age, sex, duration, and severity of
      the disease did not show a covariate effect with GH levels. There was no
      difference compared with healthy controls. CONCLUSIONS: RLS patients did not show
      an increase in GH after stimulation with low-dose apomorphine. Lack of
      sensitivity alteration of extrastriatal hypothalamic dopamine receptors suggests
      that RLS is not a general dopaminergic degenerative disease or might only show
      circadian alterations.

PMID- 17512771
TI  - Antimicrobial resistance among urinary tract Escherichia coli isolates from
      inpatients and outpatients in a tertiary care center in Sao Paulo, Brazil.

PMID- 17512772
TI  - Food poisoning due to Jimson weed mimicking Bacillus cereus food intoxication in
      Austria, 2006.

PMID- 17512773
TI  - The medical management of central nervous system infections in Uganda and the
      potential impact of an algorithm-based approach to improve outcomes.
AB  - BACKGROUND: In sub-Saharan Africa, HIV has increased the spectrum of central
      nervous system (CNS) infections. The etiological diagnosis is often difficult.
      Mortality from CNS infections is higher in sub-Saharan Africa compared to Western
      countries. This study examines the medical management of CNS infections in
      Uganda. We also propose a clinical algorithm to manage CNS infections in an
      effective, systematic, and resource-efficient manner. METHODS: We prospectively
      followed 100 consecutive adult patients who were admitted to Mulago Hospital with
      a suspected diagnosis of a CNS infection without any active participation in
      their management. From the clinical and outcome data, we created an algorithm to
      manage CNS infections, which was appropriate for this resource-limited, high HIV
      prevalence setting. RESULTS: Only 32 patients had a laboratory confirmed
      diagnosis and 23 of these were diagnosed with cryptococcal meningitis. Overall
      mortality was 39%, and mortality trended upward when the diagnosis was delayed
      past 3 days. The initial diagnoses were made clinically without significant
      laboratory data in 92 of the 100 patients. Because HIV positive patients have a
      unique spectrum of CNS infections, we created an algorithm that identified HIV
      positive patients and diagnosed those with cryptococcal meningitis. After
      cryptococcal infection was ruled out, previously published algorithms were used
      to assist in the early diagnosis and treatment of bacterial meningitis,
      tuberculous meningitis, and other common central nervous system infections. In
      retrospective comparison with current management, the CNS algorithm reduced
      overall time to diagnosis and initiate treatment of cryptococcal meningitis from
      3.5 days to less than 1 day. CONCLUSIONS: CNS infections are complex and
      difficult to diagnose and treat in Uganda, and are associated with high in
      hospital mortality. A clinical algorithm may significantly decrease the time to
      diagnose and treat CNS infections in a resource-limited setting.

PMID- 17512774
TI  - GM-CSF regulation of embryo development and pregnancy.
AB  - The reproductive tissues undergo profound structural changes and major immune
      adaptation to accommodate pregnancy. Granulocyte-macrophage colony-stimulating
      factor (GM-CSF) is one of an array of cytokines with pivotal roles in embryo
      implantation and subsequent development. Several cell lineages in the
      reproductive tract and gestational tissues synthesise GM-CSF under direction by
      ovarian steroid hormones and signalling agents originating in male seminal fluid
      and the conceptus. The pre-implantation embryo, invading placental trophoblast
      cells and the abundant populations of leukocytes controlling maternal immune
      tolerance are all subject to GM-CSF regulation. GM-CSF deficiency in pregnancy
      adversely impacts fetal and placental development, as well as progeny viability
      and growth after birth, highlighting this cytokine as a central maternal
      determinant of pregnancy outcome with clinical relevance in human fertility.

PMID- 17512775
TI  - 99mTc-HMPAO labelling inhibits cell motility and cell proliferation and induces
      apoptosis of NC-NC cells.
AB  - (99m)Tc-hexamethyl-propylenamine-oxime ((99m)Tc-HMPAO)-labelled leukocytes have
      been used in standard diagnostic procedures for the detection of infection and
      inflammation. Although some investigators have already pointed out that labelling
      of leukocytes with (99m)Tc-HMPAO has detrimental effects on the cells, still very
      little is known regarding the effects of ionizing radiation on lymphocyte
      function. The effects of (99m)Tc-HMPAO-labelling on lymphocyte adhesion,
      proliferation, mitotic index, migration and apoptosis were evaluated. The
      lymphoblastoid cell line NC-NC was used as the lymphocyte population. (99m)Tc
      HMPAO-labelling decreased cell adhesion, proliferation, mitotic index and
      motility, whereas it induced apoptosis and cell-cycle arrest. The rate of
      decrease in cell proliferation was up to 70% (P<0.001) by day 4 after labelling.
      (99m)Tc-HMPAO-labelling led a 35% decrease (P<0.001) in adhesion ability of the
      cells on fibronectin at 16h. Using the Boyden chamber motility assay, it was
      shown that both spontaneous and monocyte chemotactic protein (MCP-1)-induced
      lymphocyte motility were strongly reduced by (99m)Tc-HMPAO-labelling. The
      decrease in motility was approximately five-fold (P<0.05). In addition, a 12-fold
      increase (P<0.05) was observed in apoptosis of the (99m)Tc-HMPAO-treated cells
      compared with control cells. Besides, it was shown that cell-cycle arrest was
      induced starting from the 3rd day after treatment with (99m)Tc-HMPAO. Our
      observations indicate that (99m)Tc-HMPAO-labelling has damaging effects on
      lymphocyte function including cell adhesion, proliferation, mitotic index,
      motility and cell cycle under in vitro conditions.

PMID- 17512776
TI  - Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and genetic polymorphisms in breast
      cancer patients.
AB  - Reactive oxygen species (ROS) causes damage to DNA, but the role of ROS in breast
      carcinoma is still not clear. The objective of this study was to measure the
      urinary 8-OHdG levels of breast cancer patients at each stage of carcinogenesis
      and assess its association with the development of breast cancer. Sixty patients
      with malignant breast tumors were matched with 60 control subjects of the same
      ages in this case control study. Urinary 8-OHdG levels were significantly higher
      among breast cancer patients than among the control subjects, after making
      adjustments for confounders such as smoking, coffee consumption and use of oral
      contraceptives. The breast cancer patients were divided into three groups based
      on the stages of their cancer; urinary 8-OHdG levels decreased with each stage of
      breast carcinoma. Using multiple regression and logistic models adjusted for
      other covariates, urinary 8-OHdG levels significantly correlated with the
      development of breast cancer. However, it was found that breast cancer was not
      significantly influenced by CYP1A1, CYP1M1 or NAT2 polymorphisms. In conclusion,
      it was found that oxygen radical generation occurred within carcinoma cells, but
      the role of polymorphism of specific genes in the development of breast cancer
      should be evaluated.

PMID- 17512777
TI  - Life-threatening human metapneumovirus infections in West of Scotland.

PMID- 17512779
TI  - Prostaglandin D synthase (beta trace) levels in sleep apnea patients with and
      without sleepiness.
AB  - BACKGROUND: Excessive daytime sleepiness (EDS) occurs often in patients with
      obstructive sleep apnea syndrome (OSAS). However, not all patients present EDS.
      We hypothesized that the prostaglandin D2 system (PGD2) may be involved in the
      pathogenesis of EDS associated with OSAS. METHODS: We measured the levels of
      lipocalin-type PGD synthase (L-PGDS), the enzyme that produces PGD2, in the serum
      of 47 patients with OSAS (26 with and 21 without EDS) and 18 healthy controls.
      RESULTS: Patients with EDS had higher levels of L-PGDS (0.73+/-0.06 mg/L) than
      patients without EDS (0.58+/-0.03 mg/L, p<0.05) and controls (0.62+/-0.02 mg/L,
      p<0.05). L-PGDS levels in patients without EDS and controls were similar.
      CONCLUSION: The increased levels of circulating L-PGDS detected in OSAS patients
      with EDS suggest a possible role of the prostaglandin D system in the
      pathophysiology of daytime sleepiness in these patients.

PMID- 17512778
TI  - The Sec14-superfamily and the regulatory interface between phospholipid
      metabolism and membrane trafficking.
AB  - A central principle of signal transduction is the appropriate control of the
      process so that relevant signals can be detected with fine spatial and temporal
      resolution. In the case of lipid-mediated signaling, organization and metabolism
      of specific lipid mediators is an important aspect of such control. Herein, we
      review the emerging evidence regarding the roles of Sec14-like
      phosphatidylinositol transfer proteins (PITPs) in the action of intracellular
      signaling networks; particularly as these relate to membrane trafficking.
      Finally, we explore developing ideas regarding how Sec14-like PITPs execute
      biological function. As Sec14-like proteins define a protein superfamily with
      diverse lipid (or lipophile) binding capabilities, it is likely these under
      investigated proteins will be ultimately demonstrated as a ubiquitously important
      set of biological regulators whose functions influence a large territory in the
      signaling landscape of eukaryotic cells.

PMID- 17512780
TI  - First night efficacy of pramipexole in restless legs syndrome and periodic leg
      movements.
AB  - OBJECTIVE: Restless legs syndrome (RLS) seems to improve immediately after a
      single dose of dopamine-agonists (DA). The aim of the present study was to
      investigate the acute effects of a low standard dose of pramipexole in RLS drug
      naive patients. METHODS: A single-blind placebo-controlled study in 32
      consecutive idiopathic RLS de-novo patients was carried out. Patients who met the
      standard criteria for RLS, with a PLMS index greater than 10 as well as an RLS
      rating scale score greater than 20 underwent clinical and neurophysiological
      evaluation, hematological screening and two consecutive full-night
      polysomnographies. On the second night, all patients received 0.25mg of
      pramipexole or placebo at 9:00 p.m. Acute symptom response was assessed by a
      visual analogical scale (VAS). RESULTS: Eighteen patients received pramipexole
      and 14 patients received placebo. Compared to placebo, the single low dose
      (0.25mg) of pramipexole significantly improved RLS symptoms (VAS: from 7.4+/-1.68
      to 1.3+/-1.62, p<0.00001) and strongly reduced PLMS index (from 45.8+/-33.56 to
      9.4+/-11.40, p<0.0002). A significant increase in the percentage of stage 2 non
      rapid eye movement (NREM) sleep was also observed in the pramipexole group (from
      38.7+/-10.50 to 50.6+/-12.13, p<0.02). CONCLUSIONS: A low dose of pramipexole was
      effective in treatment-naive patients with RLS from the first night of
      administration. These results support a direct involvement of the dopaminergic
      system in RLS pathogenesis and might have important implications for a possible
      future pramipexole administration on-demand, as well as for a pharmacological
      test to confirm diagnosis in clinically complex cases.

PMID- 17512781
TI  - Childhood and adult factors associated with restless legs syndrome (RLS)
      diagnosis.
AB  - BACKGROUND AND PURPOSE: RLS appears to be caused by a complex interaction of
      genetic and environmental factors. This study sought to identify some
      environmental risk factors significantly associated with the occurrence of RLS.
      PATIENTS AND METHODS: Three adult behaviors and 10 childhood factors potentially
      related to development of RLS were evaluated for significant association with the
      occurrence of RLS in a large case-controlled family history study. All available
      family members of the probands in this study were evaluated for RLS using a
      validated diagnostic telephone interview that included a background questionnaire
      covering factors potentially associated with the development of RLS. Where
      possible, the mothers of the subjects were also interviewed regarding
      developmental factors that might affect the child's health and perhaps occurrence
      of RLS. All family members with a definite diagnosis of RLS or Not-RLS were
      included in the study. Of a total of 973 participants, 262 (27%) had RLS and 711
      did not. RESULTS: An odds ratio (OR) with 95% confidence limits (CI) was
      calculated for the relationship of each factor to RLS diagnosis. Restless sleep
      in childhood was associated with an increased risk of developing RLS later in
      life for both men (OR=2.64; 95% CI: 1.31-5.29) and women (OR=2.54; 95% CI: 1.41
      4.59). Blood donation was also significantly associated with an increased risk of
      developing RLS among men only (OR=1.99; 95% CI: 1.10-3.58), which was more
      pronounced for those donating blood more than the median number of donations for
      this group of five (OR=2.3, 95% CI: 1.16-4.43). No other factor was significantly
      associated with the occurrence of RLS. CONCLUSIONS: This is the first case
      controlled study that demonstrates a significant association between blood
      donation and the occurrence of RLS in males. The association was most significant
      for those men donating five or more times. Smoking and alcohol use were not
      related to the occurrence of RLS. Neither childhood growing pains nor attention
      deficit hyperactivity disorder (ADHD) was related to RLS. The only consistent
      factor found related to prevalence of RLS for both men and women was the report
      of 'restless sleep' in childhood.

PMID- 17512782
TI  - Voxel-based morphometry in unmedicated patients with restless legs syndrome.
AB  - BACKGROUND: The pathophysiology of restless legs syndrome (RLS) is not yet
      understood. A prior voxel-based morphometry (VBM) study reported gray matter
      increase in the pulvinar of the thalamus in a group of patients, most of whom
      were on medical treatment. Since there is evidence that medication can change the
      volume of cerebral structures, the question arises as to whether the reported
      morphometric alterations are caused by the RLS itself or, alternatively, are a
      consequence of drug treatment. To address this issue, we performed VBM in
      unmedicated RLS patients. METHODS: Fourteen patients with idiopathic RLS with no
      (n=11) or only minimal (n=3) treatment exposure in the past and 14 age- and sex
      matched healthy subjects were investigated. All subjects were free of
      psychotropic drugs for at least 4 months. Morphological data were analyzed by
      using optimized VBM. RESULTS: We did not detect any structural changes except for
      slightly increased gray matter density in the ventral hippocampus (p=0.046 on the
      left and p=0.055 on the right side) and in the middle orbitofrontal gyrus
      (p=0.046 on the right and p=0.097 on the left side). CONCLUSION: Our study could
      not confirm the findings of a prior study. A possible explanation for the
      divergent findings is the difference between the populations examined. Since, in
      our study, essentially treatment-naive patients were investigated, it is possible
      that the prior findings reflect treatment-induced effects on cerebral morphology
      in RLS.

PMID- 17512783
TI  - Prevalence and time-course of sleep-disordered breathing in patients with acute
      coronary syndrome.

PMID- 17512786
TI  - Socioeconomic status and occupation as risk factors for obstructive sleep apnea
      in Sweden: a population-based study.
AB  - OBJECTIVES: The aim of this study was to investigate whether there is an
      association between socioeconomic status, occupation and obstructive sleep apnea.
      METHODS: A nationwide database was constructed by linking the Swedish Census to
      the Hospital Discharge Register and the Cause of Death Register to obtain data on
      all first adult hospitalizations for obstructive sleep apnea diagnosed in Sweden
      during the study period from 1997 to 2001. Standardized incidence ratios (SIRs)
      with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 10,336
      male and 2,602 female first hospitalizations during the study period for
      obstructive sleep apnea were retrieved for adults aged 35 and older. The overall
      SIRs for hospitalizations for obstructive sleep apnea were close to unity between
      different socioeconomic groups and regions. Among male occupations, increased
      risks were noted for several occupational groups such as sales agents, seamen,
      drivers, engine and motor operators, and cooks and stewards. For female
      occupations, an increased risk was observed only among drivers. Adjustment for
      obesity had no effect on the risk levels. CONCLUSIONS: Socioeconomic status and
      occupation have a minor effect on the population's likelihood of hospitalization
      for obstructive sleep apnea. Although the increased risks found for seamen,
      engine and motor operators, and cooks and stewards may be partly explained by
      their work-related exposure, residual confounding due to smoking and alcohol
      might be present.

PMID- 17512787
TI  - Effect of CPAP on QT interval dispersion in obstructive sleep apnea patients
      without hypertension.
AB  - OBJECTIVES: Delayed cardiac repolarization leading to prolongation of the QT
      interval is a well-characterised precursor of arrhythmias. Obstructive sleep
      apnea (OSA) might cause arrhythmias, since QT corrected interval dispersion
      (QTcd) is increased in these patients. We aimed to determine the effect of nasal
      continuous positive airway pressure (CPAP) therapy on QTcd in OSA patients
      without hypertension. METHODS: An overnight polysomnography (PSG) and a standard
      12-lead electrocardiogram (ECG) were performed on 49 subjects without
      hypertension, diabetes mellitus, cardiac or pulmonary disease or any hormonal,
      hepatic, renal or electrolyte disorders. In 29 moderate-severe OSA (apnea
      hypopnea index: AHI15) patients, QTd (defined as the difference between the
      maximum and minimum QT interval) and QTcd were calculated using the Bazzet
      formula at baseline and after six months of CPAP therapy. RESULTS: Eighteen
      patients were compliant with nasal CPAP, and mean age was 46.5+/-4.9 years.
      Patients had high body mass index (BMI: 30.6+/-4.0 kg/m(2)), but there was no
      change in either BMI or blood pressure after six months. A strong positive
      correlation was shown between QTcd and AHI (p<0.001, r=0.913). The QTcd at
      baseline (54.5+/-8.7 ms) significantly decreased after CPAP therapy (35.5+/-4.2
      ms, p<0.001), although it did not significantly change in 11 non-compliant
      patients. CONCLUSION: In OSA patients without hypertension, CPAP therapy improves
      the inhomogeneity of repolarization via a significant decrease in QTcd.

PMID- 17512788
TI  - Predicting effective continuous positive airway pressure in sleep apnea using an
      artificial neural network.
AB  - BACKGROUND: Mathematical formulas have been less than adequate in assessing the
      optimal continuous positive airway pressure (CPAP) level in patients with
      obstructive sleep apnea (OSA). The objectives of the study were (1) to develop an
      artificial neural network (ANN) using demographic and anthropometric information
      to predict optimal CPAP level based on an overnight titration study and (2) to
      compare the predicted pressures derived from the ANN to the pressures computed
      from a previously described regression equation. METHODS: A general regression
      neural network was used to develop the predictive model. The derivation cohort
      included 311 consecutive patients who underwent CPAP titration at a University
      affiliated Sleep Center. The model was validated subsequently on 98 participants
      from a private sleep laboratory. RESULTS: The correlation coefficients between
      the optimal pressure determined by the titration study and the predicted pressure
      by the ANN were 0.86 (95% confidence interval [CI] 0.83-0.88; p<0.001) for the
      derivation cohort and 0.85 (95% CI 0.78-0.9; p<0.001) for the validation cohort,
      respectively. Whereas there was no significant difference between the optimal
      pressure obtained during overnight polysomnography and the predicted pressure
      estimated by the ANN (p=0.4), the estimated pressure derived from the regression
      equation underestimated the optimal pressure in both the derivation and the
      validation group, respectively. CONCLUSION: The optimal CPAP level predicted by
      the ANN provides a more accurate assessment of the pressure derived from the
      historic regression equation.

PMID- 17512789
TI  - A 52-week open-label study of the long-term safety of ropinirole in patients with
      restless legs syndrome.
AB  - OBJECTIVE: To assess the long-term safety and efficacy of ropinirole in the
      treatment of patients with restless legs syndrome (RLS) over 52 weeks. METHODS: A
      52-week, multicentre, open-label continuation study involving 310 patients,
      conducted in 11 countries. Eligible patients from four parent studies were
      invited to participate. At parent study entry, all patients had a score of > or
      =15 on the International Restless Legs Scale (IRLS). In this continuation study,
      all participants received ropinirole, 0.25-4.0 mg once daily, for 52 weeks. The
      primary study objective was to evaluate the safety of ropinirole. Efficacy was
      assessed by change in IRLS score, as well as by global improvements (clinical
      global impression [CGI] scale) and improvements in measures of sleep, work
      productivity, and quality of life. RESULTS: Overall, 251 (81.0%) patients
      completed the study. The mean ropinirole dose at study end was 1.90 mg/day. A
      total of 282 patients (91.3%) reported > or = 1 adverse event. For the majority
      of patients, the reported adverse events were mild or moderate in intensity. The
      most common adverse event was nausea. Adverse events led to discontinuation in
      8.7% of patients. At week 52, IRLS scores improved by an average of 12.0 points
      from baseline, and 82.8% of patients were 'much improved' or 'very much improved'
      on the CGI-improvement scale. Ropinirole treatment was also associated with
      improvements in measures of sleep and quality of life. CONCLUSIONS: Ropinirole
      was well tolerated and therapeutic efficacy was maintained over 52 weeks in
      patients with RLS.

PMID- 17512790
TI  - Use of alcohol and hypnotic medication as aids to sleep among the Japanese
      general population.
AB  - OBJECTIVE: The present study was conducted to clarify the prevalence of the use
      of alcohol and hypnotic medication as sleep aids, and associated factors, in the
      general population in Japan. METHODS: The survey was conducted in June 2000,
      using self-administered questionnaires, targeting a population that was selected
      randomly from among 300 communities throughout Japan. A total of 18,205 responses
      indicating alcohol use and 16,804 responses indicating hypnotic medication use
      were analyzed. RESULTS: The prevalence of alcohol use as a sleep aid one or more
      times per week was 48.3% among men and 18.3% among women. The prevalence of the
      use of hypnotic medication one or more times per week was 4.3% among men and 5.9%
      among women. The prevalence of alcohol used as a sleep aid increased gradually
      for men and women up to age 55-59 years and 40-44 years, respectively, and then
      declined with increasing age thereafter. The prevalence of the use of hypnotic
      medication among both men and women showed a trend toward a gradual increase with
      age. The use of alcohol as a sleep aid was associated with "difficulty
      maintaining sleep," but no such problem was associated with the use of hypnotic
      medication. CONCLUSIONS: Alcohol is a more popular sleep aid than hypnotic
      medication. The factors associated with the use of alcohol and of hypnotic
      medication are different.

PMID- 17512792
TI  - A reliable change index (RCI) for the Epworth sleepiness scale (ESS).

PMID- 17512791
TI  - CPAP causing peripheral oedema: Uncommon but not unknown.

PMID- 17512793
TI  - REM sleep behavior disorder and other sleep disturbances in Disney animated
      films.
AB  - During a viewing of Disney's animated film Cinderella (1950), one author (AI)
      noticed a dog having nightmares with dream-enactment that strongly resembled RBD.
      This prompted a study in which all Disney classic full-length animated films and
      shorts were analyzed for other examples of RBD. Three additional dogs were found
      with presumed RBD in the classic films Lady and the Tramp (1955) and The Fox and
      the Hound (1981), and in the short Pluto's Judgment Day (1935). These dogs were
      elderly males who would pant, whine, snuffle, howl, laugh, paddle, kick, and
      propel themselves while dreaming that they were chasing someone or running away.
      In Lady and the Tramp the dog was also losing both his sense of smell and his
      memory, two associated features of human RBD. These four films were released
      before RBD was first formally described in humans and dogs. In addition,
      systematic viewing of the Disney films identified a broad range of sleep
      disorders, including nightmares, sleepwalking, sleep related seizures, disruptive
      snoring, excessive daytime sleepiness, insomnia and circadian rhythm sleep
      disorder. These sleep disorders were inserted as comic elements. The inclusion of
      a broad range of accurately depicted sleep disorders in these films indicates
      that the Disney screenwriters were astute observers of sleep and its disorders.

PMID- 17512794
TI  - Sleep improvement in an insomniac patient with global pituitary insufficiency
      after change from triple to quadruple cortisol replacement therapy.
AB  - Although cortisol has a distinct circadian rhythm, patients with adrenal
      insufficiency usually receive diurnal hydrocortisone replacement therapy (HRT),
      disregarding possible consequences for sleep quality. The case reported here
      concerns the resolution of severe insomnia in a patient with global hypopituitary
      insufficiency upon adjustment of triple HRT to quadruple HRT. The data show a
      strong influence of cortisol on total sleep time and slow wave sleep (SWS) as
      well as rapid eye movement (REM) sleep. Clinically, the data are suggestive of
      the need to assimilate HRT to the natural circadian cortisol rhythm and not
      restrict it to the active part of the day.

PMID- 17512795
TI  - Long-term oxygen administration reduces plasma adrenomedullin levels in patients
      with obstructive sleep apnea syndrome.
AB  - BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is recognized as
      one of the risk factors of hypertension and cardiovascular disorders. In the
      current study, we hypothesized that the hypoxic stress caused by obstructive
      sleep apnea would increase circulating adrenomedullin (ADM) levels in untreated
      OSAS patients compared to an age-matched control group. We further hypothesized
      that oxygen administration treatment may decrease OSAS-induced hypoxic stress and
      ADM levels. METHODS: We examined short-term and long-term oxygen administration
      effects on circulating ADM in 48 OSAS patients. RESULTS: The circulating levels
      of ADM in untreated OSAS patients were significantly greater than those in the
      controls. We did not observe a significant effect in 2 weeks of oxygen
      administration on the circulating ADM in the patients, but we observed a
      significant effect in long-term oxygen administration for more than 3 months on
      plasma ADM levels. Long-term oxygen therapy decreased both the magnitude of
      arterial oxygen desaturation and plasma ADM levels in patients but did not
      decrease blood pressure. CONCLUSIONS: These observations suggest that long-term
      oxygen therapy could reduce OSAS-induced nocturnal hypoxemia and plasma ADM
      levels in patients with OSAS.

PMID- 17512797
TI  - Health-related quality of life in patients with narcolepsy.
AB  - BACKGROUND: To evaluate the health-related quality of life (HRQoL) in patients
      suffering from narcolepsy. METHODS: Subjects included 75 narcoleptic patients
      diagnosed at the Hephata Klinik, Germany, who met the International
      Classification of Sleep Disorders (ICSD) criteria for narcolepsy. A standardized
      telephone interview was used to inquire about the disease and its burdens to the
      patients. HRQoL was recorded using the 36-item short-form Medical Outcomes Study
      (SF-36) as well as the Euroqol (EQ-5D). Frequency and factors of influence on
      decreased HRQoL were evaluated by using bivariate and multivariate analyses.
      RESULTS: Patients with narcolepsy had considerably lower scores on all eight
      domains of the SF-36 compared to the general German population. In particular,
      scores were poor for the dimensions "physical role", "vitality", and "general
      health perception". Forty-eight percent of the patients reported problems in at
      least one of the EQ-5D items; most frequent were problems in the dimension "usual
      activity" (63.8%), "pain/discomfort" (61.7%) and "anxiety/depression" (41.1%).
      Difficulty maintaining "self-care" was documented only by 6.8%. The mean VAS
      score was 60.7%. Interestingly, signs and symptoms of narcolepsy, except for
      irresistible sleep episodes (p<0.03), had only a minor impact on HRQoL.
      Multivariate analyses confirmed a strong influence of employment status, living
      with a partner, excessive daytime sleepiness (EDS) and professional advancement.
      CONCLUSIONS: HRQoL is considerably reduced in patients, with narcolepsy affecting
      the different dimensions to various degrees. Factors other than clinical signs
      and symptoms are associated also with poor HRQoL. Measures should be taken to
      integrate those factors into healthcare guidelines in order to improve the
      quality of life in patients with narcolepsy.

PMID- 17512798
TI  - Why do we continue to use Epworth sleepiness scale?

PMID- 17512799
TI  - A pilot study evaluating acute use of eszopiclone in patients with mild to
      moderate obstructive sleep apnea syndrome.
AB  - OBJECTIVE: To evaluate the effects of eszopiclone on measures of respiration and
      sleep using polysomnography in patients with mild to moderate obstructive sleep
      apnea syndrome (OSAS). METHODS: This double-blind, randomized crossover study
      included patients (35-64 years) with mild-to-moderate OSAS [apnea and hypopnea
      index (AHI) range 10 and 40]. Patients received either eszopiclone 3mg or placebo
      for two consecutive nights, with a 5-7 day washout between treatments. Continuous
      positive airway pressure (CPAP) was not allowed on nights in the sleep
      laboratory. RESULTS: The primary endpoint, mean total AHI, was not significantly
      different from placebo (16.5 with placebo and 16.7 with eszopiclone; 90%
      confidence interval (CI) -1.7, 1.9). No significant differences in total
      arousals, respiratory arousals, duration of apnea and hypopnea episodes, or
      oxygen saturation were noted. Significant differences in spontaneous arousals
      (13.6 versus 11.4 for placebo and eszopiclone, respectively; 90% CI -3.7, -0.7),
      sleep efficiency (85.1% and 88.4%; p=0.0075), wake time after sleep onset (61.8
      and 48.1 min; p=0.0125), and wake time during sleep (55.9 and 43.2 min; p=0.013)
      were noted after eszopiclone treatment. Eszopiclone was well tolerated.
      CONCLUSIONS: In this pilot study, eszopiclone did not worsen AHI, and it improved
      sleep maintenance and efficiency. Further study is warranted to determine whether
      eszopiclone could improve CPAP compliance or next-day function in patients with
      OSAS.

PMID- 17512800
TI  - Autonomic dysfunction characterizes also subjects with obstructive sleep apnea
      and normal glucose regulation.

PMID- 17512801
TI  - CLIP proteases and Plasmodium melanization in Anopheles gambiae.
AB  - Melanization is a potent immune response mediated by phenoloxidase (PO). Multiple
      Clip-domain serine proteases (CLIP) regulate PO activation as part of a complex
      cascade of proteases that are cleaved sequentially. The role of several CLIP as
      key activators or suppressors of the melanization responses of Anopheles gambiae
      to Plasmodium berghei (murine malaria) has been established recently using a
      genome-wide reverse genetics approach. Important differences in regulation of PO
      activation between An. gambiae strains were also identified. This review
      summarizes these findings and discusses our current understanding of the An.
      gambiae melanization responses to Plasmodium.

PMID- 17512802
TI  - Nurse educational activity on non-prescription therapies in patients with chronic
      heart failure.
AB  - BACKGROUND: Notwithstanding the polypharmacy required for heart failure therapy,
      many patients use non-prescription therapies, including alternative medicines,
      herbal remedies, integrators and over-the-counter (OTC) drugs. AIMS: Non
      prescription therapies could interfere with heart failure therapy, both promoting
      non-compliance and through pharmacological interferences. Heart failure nurses,
      in order to plan their educational activity, need to known about the use of
      therapies other than prescription. METHODS: The use of non-prescription therapies
      was assessed by a structured interview in 153 chronic patients with heart
      failure. RESULTS: Only 15.7% patients exclusively used medicines prescribed by
      their physicians. Alternative medicine use was not frequent (5.8%), herbal
      remedies (21.3%) and integrators (20.9%) were more used; OTC drugs were most
      common, with 75.8% use. Patients were often unaware of possible interaction with
      heart failure therapies, and seldom informed physician of use. CONCLUSIONS:
      Advice about drugs avoidance is emphasized by heart failure guidelines, and is
      part of the nurse educational activity. More attention should be paid to OTC drug
      assessment and education since their use is common.

PMID- 17512804
TI  - Lung gas transfer in children with sickle cell anaemia.
AB  - The impact of sickle cell anaemia (SCA) on respiratory function of children must
      be determined if their management is to be optimised. Pulmonary diffusing
      capacity (DL(CO)), corrected for haemoglobin (DL(COc)), therefore was assessed in
      24 children with SCA and 24 ethnic matched controls, mean age 11 (range 7-16)
      years. To determine if any differences found correlated with other measures of
      lung function, spirometry was undertaken and lung volumes assessed. The SCA
      children compared to the controls had lower weight (p=0.01), body mass index
      (p=0.002), DL(CO) (p<0.0001), K(CO) (p=0.003), V(CSB) (p=0.01), FEV(1) (p<0.0001)
      and FVC (p<0.0001), but greater K(COc) (p=0.001). K(COc) results correlated
      significantly with PEF (r=-0.58, p=0.02), but not TLC(pleth) (p=0.36), FEV(1)
      (0.39) or FVC (p=0.36). In conclusion, when corrected for haemoglobin levels, the
      SCA children compared to controls of similar age had elevated gas transfer per
      unit lung volume results. Our results suggest this abnormality is independent of
      other lung function abnormalities.

PMID- 17512805
TI  - HPLC quantification of perphenazine in sheep plasma: application to a
      pharmacokinetic study.
AB  - A high performance liquid chromatographic (HPLC) method for the determination of
      perphenazine (PPZ) in sheep plasma was developed and validated. The separation
      was achieved using a 5 microm C18 column (125 mm x 4 mm) with a mobile phase
      composed of acetonitrile and an aqueous solution of H(3)PO(4) and TBA (inverse
      gradient). The flow rate was 1.5 mL/min and the UV detection was performed at 258
      nm. The method was validated with respect to linearity, intra and inter-day
      precision and accuracy, limit of quantification, limit of detection and storage
      stability. This method was used to perform a pilot pharmacokinetic study of PPZ
      after subcutaneous administration to one ewe.

PMID- 17512803
TI  - Impaired in vitro regulatory T cell function associated with Wiskott-Aldrich
      syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency characterized by the
      contradictory coexistence of impaired T-cell function and exaggerated T-cell
      mediated pathology, including autoimmunity and eczema. WAS protein (WASp)
      deficient mice are also immunodeficient and can develop autoimmune disease. Since
      defects in regulatory T-cells (Treg) are associated with autoimmunity, we
      examined the presence and function of these cells in WAS patients and WASp
      deficient mice. We found that CD4(+)CD25(+)FOXP3(+) Treg cells can develop in the
      absence of WASp expression. However, Treg cells both from WASp-deficient mice and
      from four out of five WAS patients studied showed impaired in vitro suppressor
      function. In WASp-deficient mice, this defect could be partially rescued by pre
      activation with IL-2, suggesting that inadequate cell activation may play a role
      in WASp-deficient Treg dysfunction. These findings may provide insights into the
      complex pathophysiology and paradoxical phenotypes of WAS and suggest new
      therapeutic modalities for autoimmunity in these patients.

PMID- 17512806
TI  - Functional duplication of ligand-binding domains within low-density lipoprotein
      receptor-related protein for interaction with receptor associated protein, alpha2
      macroglobulin, factor IXa and factor VIII.
AB  - The low-density lipoprotein receptor-related protein (LRP) binds a range of
      proteins including receptor associated protein (RAP), activated alpha2
      macroglobulin (alpha2M*), factor IXa (FIXa), and factor VIII (FVIII) light chain.
      The binding is mediated by the complement-type repeats, which are clustered in
      four distinct regions within LRP. Cluster II of 8 repeats (CR3-10) and cluster IV
      of 11 repeats (CR21-31) have been implicated in ligand-binding. Previous studies
      have aimed to identify the cluster II repeats involved in binding alpha2M* and
      RAP. We now evaluated the binding to RAP, alpha2M*, FIXa and FVIII light chain of
      triplicate repeat-fragments of not only clusters II but also of cluster IV.
      Employing surface plasmon resonance analysis, we found that most efficient ligand
      binding was displayed by the repeats within region CR4-8 of cluster II and within
      region CR24-28 of cluster IV. Whereas the binding to RAP could be attributed to
      two consecutive repeats (CR5-6, CR26-27), combinations of three repeats showed
      most efficient binding to FIXa (CR6-8, CR26-28), FVIII light chain (CR5-7, CR6-8,
      CR24-26), and alpha2M* (CR4-6, CR24-26). The results imply that there is an
      internal functional duplication of complement-type repeats within LRP resulting
      in two clusters that bind the same ligands.

PMID- 17512807
TI  - Self-assembly of nano-hydroxyapatite on multi-walled carbon nanotubes.
AB  - Inspired by self-assembly of nano-hydroxyapatite (nHA) on collagen associated
      with the 67nm periodic microstructure of collagen, we used multi-walled carbon
      nanotubes (MWCNTs) with approximately 40nm bamboo periodic microstructure as a
      template for nHA deposition to form a nHA-MWCNT composite. The assembled apatite
      was analyzed by transmission electron microscopy and scanning electron
      microscopy. Defects that were analogous to edge dislocations along the carbon
      nanotubes' multi-walled surfaces were the nucleation sites for nHA after these
      defects had been functionalized principally into carboxylic groups. Spindle
      shaped units consisting of an assembly of near parallel, fibril-like nHA
      polycrystals were formed and oriented at a certain angle to the long axis of the
      carbon nanotubes, unlike nHA-collagen in which the nHA is oriented along the
      longitudinal axis of the collagen molecule. One possible explanation for this
      difference is that there are more bonds for calcium chelation (-COOH, >CO) on the
      collagen fibril surface than on the surface of MWCNTs. Spindle-shaped units that
      are detached from the MWCNT template are able to maintain the ordered parallel
      structure of the nHA polycrystal fibril. We have thus created a self-assembled
      hydroxyapatite on MWCNTs.

PMID- 17512808
TI  - Influence of strontia on various properties of surgical simplex P acrylic bone
      cement and experimental variants.
AB  - The fact that the composition of acrylic bone cement, as used in cemented primary
      arthroplasties, is not optimal has been highlighted in the literature. For
      example: (i) deleterious effects of the radiopacifier (BaSO(4) or ZrO(2)
      particles in the powder) have been reported; (ii) there is an indication that pre
      polymerized poly(methylmethacrylate) (PMMA) beads in the powder may be dispensed
      with; and (iii) there is a strong consensus that the accelerator commonly used,
      N,N-dimethyl-p-toluidine (DMPT), is toxic and has many other undesirable
      properties. At the same time, the effectiveness of drugs that contain a strontium
      compound in treating the effects of osteoporosis has been explained in terms of
      the role of strontium in bone formation and resorption. This indicates that
      strontium compounds may also have desirable effects on osseointegration of
      arthroplasties. The present study is a detailed evaluation of 24 acrylic bone
      cement formulations comprising different relative amounts of BaSO(4), strontia
      (as an alternative radiopacifier), pre-polymerized PMMA beads and DMPT. A large
      number of properties of the curing and cured cement were determined, including
      setting time, polymerization rate, fracture toughness and fatigue life. The focus
      was on the radiopacifier, with the finding being that many properties of
      formulations that contained strontia were about the same or better than those for
      cements that contained BaSO(4). Thus, further developmental work on strontia
      containing acrylic bone cements is justified, with a view to making them
      candidates for use in cemented primary arthroplasties.

PMID- 17512809
TI  - Conversion of sea urchin spines to Mg-substituted tricalcium phosphate for bone
      implants.
AB  - The skeleton of sea urchin spines is composed of large single crystals of Mg-rich
      calcite, which have smooth, continuously curved surfaces and form a three
      dimensional fenestrated mineral network. Spines of the echinoids Heterocentrotus
      trigonarius and Heterocentrotus mammillatus were converted by the hydrothermal
      reaction at 180 degrees C to bioresorbable Mg-substituted tricalcium phosphate
      (beta-TCMP). Due to the presence of Mg in the calcite lattice, conversion to beta
      TCMP occurs preferentially to hydroxyapatite formation. The converted beta-TCMP
      still maintains the three-dimensional interconnected porous structures of the
      original spine. The main conversion mechanism is the ion-exchange reaction,
      although there is also a dissolution-reprecipitation process that forms some
      calcium phosphate precipitates on the surfaces of the spine network. The average
      fracture strength of urchin spines and converted spines (beta-TCMP) in the
      compression tests are 42 and 23MPa, respectively. In vivo studies using a rat
      model demonstrated new bone growth up to and around the beta-TCMP implants after
      implantation in rat femoral defects for 6 weeks. Some new bone was found to
      migrate through the spine structural pores, starting from the outside of the
      implant through the pores at the edge of the implants. These results indicate
      good bioactivity and osteoconductivity of the porous beta-TCMP implants.

PMID- 17512810
TI  - The role of medial gastrocnemius free flap in coverage of ischial pressure sore
      in paraplegic patients.
AB  - Pressure sores, and especially ischial pressure sores, are a serious concern in
      the life of paraplegic patients. The treatment of this pathology is obviously
      surgery, and several local flaps can be used for coverage. However, recurrent
      pressure sores in an active patient can be frustrating if all local flaps have
      been used. Free flaps are therefore the next option. In our experience, the free
      medial gastrocnemius musculocutaneous flap is the best option. This paper reports
      the closure of ischial pressure sores with a free medial gastrocnemius flap, the
      patient selection criteria used, and the postoperative care provided.

PMID- 17512811
TI  - The evolution and refinements of the distally based dorsal metacarpal artery
      (DMCA) flaps.
AB  - Distally based DMCA flaps are well established in reconstructive hand surgery.
      They comprise the dorsal flap described by Quaba and the DMCA flaps described by
      Earley, Milner and others. The most frequent indications for these flaps are soft
      tissue defects of the dorsum of the proximal phalanx and the total length of the
      finger. Since its introduction several modifications have been developed to match
      specific defect requirements; these include: the development of pure fascial DMCA
      flaps, the use of DMCA flaps in dorsally grafted burned hands and modifications
      in design to avoid 'tunnelling' and to permit skin-skin defect closure. The
      purpose of this article is to provide an overview of the evolution and
      refinements of the DMCA flaps based on the experience of a single centre. The
      DMCA flaps provide one stage coverage of excellent quality with independent
      vascularisation and permit primary closure of the recipient site without
      sacrificing relevant arteries (e.g. proper digital artery). However, the DMCA
      flaps also possess drawbacks, for example, apart from the fact that this
      technique is quite demanding, possible hair growth and a visible scar on the
      exposed dorsal part of the hand present aesthetic problems for some patients.
      Despite these limitations, DMCA flaps are considered to be extremely useful.

PMID- 17512812
TI  - Is it justified to refuse breast reduction to smokers?
AB  - INTRODUCTION AND AIMS: There are several studies in the literature suggesting
      that smoking increases the complication rate in various plastic surgery
      operations. We did a study on 402 patients to see the effect of smoking on breast
      reduction. The objective was to raise the controversial issue of whether breast
      reduction could be refused to smokers who fail to stop smoking in the peri
      operative period. MATERIALS AND METHODS: The records of patients who had
      undergone breast reductions between April 1999 and May 2004 at the Leicester
      Royal Infirmary, Leicester were reviewed retrospectively for age, body mass
      index, smoking habits and wound-related complications. RESULTS: A total of 764
      breast reductions were performed in 402 patients during this period. Twenty-eight
      per cent (112) of these patients were smokers. The mean age was 33.9 (range 19
      68)+9.5 years in smokers and 34.4 (range 16-73)+10.6 years in non-smokers. About
      90% of patients had bilateral breast reductions. Wound-related complications were
      seen in 35% of smokers as against 13% of non-smokers, P value<0.001. Overall,
      smokers had a 2.3 x higher chance of developing a complication. The probability
      of a smoker developing wound infection was 3.3 x more in comparison to a non
      smoker. Smokers were also three times more likely to develop T-junction necrosis.
      CONCLUSION: Smoking increases the complication rate of breast reduction
      significantly. Hence, patients must be strongly encouraged to quit smoking before
      surgery and abstain until the wound has completely healed. Stoppage of smoking in
      the peri-operative period should be adopted as an essential eligibility criterion
      for breast reduction.

PMID- 17512813
TI  - A 2.6 Mb deletion of 6q24.3-25.1 in a patient with growth failure, cardiac septal
      defect, thin upperlip and asymmetric dysmorphic ears.
AB  - We report a female patient with neurodevelopmental delay and peculiar facial
      features. She has postnatal growth failure and an atrial septal defect. Patent
      duct arteriosis and tricuspidal insufficiency were also noted at birth.
      Characteristic facial features include medial flare eyebrows, dysmorphic helix of
      the right ear, cupshaped left ear, anteverted nares, long and smooth philtrum,
      thin upper lip, high vaulted palate. Array-CGH analysis demonstrated the presence
      of a 2.6 Mb deletion in 6q24.3-25.1. The phenotypic features of this case are
      very similar to those previously reported in a patient with a 7Mb overlapping
      deletion, pointing to a specific new syndrome. Twenty-two genes are present in
      the common critical deleted region. Among them, there is the PPP1R14C gene that
      encodes for KEPI, a PKC-potentiated inhibitory protein for type-1 Ser/Thr protein
      phosphatase. Its selective distribution in brain and heart well correlates with
      developmental delay and cardiac anomalies observed in the patient.

PMID- 17512814
TI  - Sialylation of cell surface glycoconjugates is essential for osteoclastogenesis.
AB  - Sialic acid, which is located at the end of the carbohydrate moiety of cell
      surface glycoconjugates, is involved in many biologic responses, such as
      intercellular reactions and virus-cell fusion, especially in hematopoietic cells.
      Here we provide experimental evidence that the sialic acid of cell surface
      glycoconjugates has a role in osteoclast differentiation. Lectin histochemical
      study demonstrated the existence of both alpha (2,3)-linked-sialic acid and alpha
      (2,6)-linked-sialic acid in mouse bone marrow-derived macrophages and in the
      RAW264.7 macrophage cell line, which are osteoclast precursors. Flow cytometric
      analysis of surface lectin staining revealed the kinetics of these sialic acids
      during osteoclastogenesis: alpha (2,3)-linked-sialic acid was abundantly
      expressed throughout osteoclastogenesis, whereas alpha (2,6)-linked-sialic acid
      levels declined at the terminal stage of osteoclast differentiation. To
      investigate the role of sialic acid in osteoclast differentiation, we performed
      an osteoclastogenesis assay with or without exogenous sialidase treatment.
      Desialylated cells formed TRAP-positive mononuclear cells, but did not become
      multinuclear cells despite the normal expression of osteoclast markers such as
      cathepsin K, integrin beta3, and nuclear factor-ATc1. Flow cytometric analysis
      also demonstrated that exogenous sialidase effectively removed alpha (2,6)-linked
      sialic acid, but only slightly changed the alpha (2,3)-linked-sialic acid
      content, suggesting that alpha (2,6)-linked-sialic acid might be involved in
      osteoclast differentiation. Findings from knockdown analysis using small
      interfering RNA oligonucleotides against alpha 2,6-sialyltransferase support this
      idea: alpha (2,6)-linked-sialic acid-deficient cells markedly inhibit the
      formation of multinuclear osteoclasts. Our findings suggest that alpha (2,6)
      linked-sialic acid of cell surface glycoconjugates has a role in osteoclast
      differentiation, possibly via its role in the cell-cell fusion process.

PMID- 17512815
TI  - Molecular imprinted polymer-based chemiluminescence imaging sensor for the
      detection of trans-resveratrol.
AB  - Sensitive, rapid and inexpensive chemiluminescence (CL) imaging has been
      developed based on molecular imprinted polymer (MIP) sensing elements. Imprinted
      uniform microspheres were synthesized by precipitation polymerization. Microtiter
      plates (96 wells) were coated with polymer microspheres imprinted with trans
      resveratrol, which were fixed in place using poly(vinyl alcohol) (PVA) as glue.
      The amount of polymer-bound trans-resveratrol was quantified using imidazole
      (IMZ)-catalyzed peroxyoxalate chemiluminescence (PO-CL) reaction. The light
      produced was then measured with a high-resolution CCD camera. Calibration curve
      corresponding to analyte concentration ranging from 0.3 to 25 microg mL(-1) was
      obtained with a limit of detection 0.1 microg mL(-1). These results showed that
      the MIP-based CL imaging sensor can become a useful analytical tool for quick
      simultaneous detection of trans-resveratrol in a large number of real samples.

PMID- 17512816
TI  - Analysis of berberine and total alkaloid content in cortex phellodendri by near
      infrared spectroscopy (NIRS) compared with high-performance liquid chromatography
      coupled with ultra-visible spectrometric detection.
AB  - This paper developed a rapid method using near infrared spectroscopy (NIRS) to
      differentiate two species of cortex phellodendri (CP), cortex phellodendri
      chinensis (PCS) and cortex phellodendri amurensis (PAR), and to predict
      quantitatively the content of berberine and total alkaloid content in all cortex
      phellodendri samples. Three alkaloids, berberine, jatrorrhizine and palmatine
      were analyzed simultaneously with a Thermo ODS Hypersil column by gradient
      elution with a new mobile phase under high-performance liquid chromatography
      diode array detection (HPLC-DAD). Berberine content determined by HPLC-DAD was
      exploited as a critical parameter for successful discrimination between them.
      Multiplicative scatter correction (MSC), second derivative and Savitsky-Golay
      (S.G.) were utilized together to correct the scattering effect and eliminate the
      baseline shift in all near infrared diffuse reflectance spectra as well as to
      enhance spectral features in order to give a better correlation with the results
      obtained by HPLC-DAD. With the use of principal component analysis (PCA), samples
      datasets were separated successfully into two different clusters corresponding to
      two species. Furthermore, a partial least squares (PLS) regression method was
      built on the correlation model. The results showed that the correlation
      coefficients of the prediction models were R=0.996 for the berberine and R=0.994
      for total alkaloid content. The influences of water absorption bands present in
      the NIR spectra on the models were also investigated in order to explore the
      practicability of NIRS in routine use. The outcome showed that NIRS possibly acts
      as routine screening in the quality control of Chinese herbal medicine.

PMID- 17512817
TI  - A comparative analysis of polyurethane hydrogel for immobilization of IgG on
      chips.
AB  - Hydrogels are considered an optimum material for protein chip surfaces, since
      they provide a quasi-liquid environment which allows protein activity to be
      maintained and shows good spot morphology as well as excellent immobilization
      capacity. In the following, we present a polyurethane (PU) chip that
      electrostatically binds IgG. The PU surface is optimized with regard to layer
      thickness (approximately 200 nm), hydrogel (2%) and immobilized antibody
      concentration (0.5 mg mL(-1); 0.3 ng spot(-1)), pH and ionic strength of the
      print buffer as well as to blocking solution. Evaluation is done in a direct IgG
      immunoassay using the Nexterion slide H as a reference. It is shown that higher
      IgG loading is achieved on the PU chip than on slide H, no matter whether 1x PBS
      (pH 7.2), Sorensen (pH 5.8) or Nexterion buffer was used as a spotting solution.
      Moreover, the crossreactivity with goat IgG, human IgG and monoclonal anti-CRP
      spotted in Nexterion buffer was as low as < or = 0.74% (slide H: < or = 3.34%).

PMID- 17512818
TI  - Quantification of very low enantiomeric impurity of efaroxan using a dual
      cyclodextrin system by capillary electrophoresis.
AB  - A rapid method for the enantiomeric purity determination of efaroxan has been
      developed by capillary electrophoresis (CE) using a dual cyclodextrin (CD)
      system. The influence of the nature and the concentration of CDs on separation
      parameters has been studied. High resolution (R(s)=7) and peak efficiency
      (104,000-121,000 theoretical plates) values were obtained for efaroxan
      enantiomers by adding two cyclodextrins, one neutral (7.5 mM DM-beta-CD) and the
      other negatively charged (3 mM CM-beta-CD) to the running buffer composed of 100
      mM phosphoric acid-triethanolamine (pH 3). These resolution and peak efficiencies
      values allowed the quantitation of the (S)-enantiomer of efaroxan at very low
      enantiomeric excess even if the minor component migrates after the major one.
      This method was fully validated for the enantiomeric impurity determination of
      the (S)-form of efaroxan at the 0.05% level. Calibration curve, expressed by the
      peak areas ratio versus the enantiomeric purity was linear over the 0.05-1%
      enantiomeric impurity range (r2=0.9996). Limits of detection (LOD) and
      quantification (LOQ), expressed in term of (S)-enantiomer impurity were 0.02% and
      0.05%, respectively. The accuracy of the method at 0.12%, 0.50% and 0.80%
      enantiomeric impurity levels for the (S)-form were determined. Recoveries were in
      94-102% range for each quality control sample and were determined with good
      precision (intra-day R.S.D.=3.54%, inter-day R.S.D.=5.33%).

PMID- 17512819
TI  - Glycosyl linkage characteristics and classifications of exo-polysaccharides of
      some regionally different strains of Lentinula edodes by amplified fragment
      length polymorphism assay and cluster analysis.
AB  - We report here the first combined amplified fragment length polymorphism (AFLP)
      analysis of genomic DNA fingerprinting data and cluster analysis of the exo
      polysaccharide glycosyl linkage data of 10 regionally different strains of
      Lentinula edodes to compare their genetic and structural similarities and
      differences. In addition, the monosaccharide compositions, molecular weights,
      glycosyl structural linkages were investigated for the exo-polysaccharides
      extracted from these different phylogenetic groups of regionally different L.
      edodes. All exo-polysaccharides had similar molecular weight distribution between
      1x10(4) and 3x10(6) Da and the monosaccharide composition analysis revealed the
      presence of heterogeneous materials containing glucose, mannose, xylose,
      galactose, fucose, rhamnose and arabinose in different ratios. Among these
      monosaccharides, the glucose contents are the highest for all but one strain,
      indicating that glucose probably is the building block of the backbones of these
      exo-polysaccharides. The AFLP assay data helped to classify the 10 L. edodes
      strains into three distinct genetic groups. Gas chromatographic and mass
      spectrometric (GC-MS) data revealed five different glycosyl linkage types for
      these exo-polysaccharides. Most of the exo-polysaccharide backbone structures
      contain (1-->4)-linked-D-glucopyranosyl and (1-->6)-linked-D-glucopyranosyl
      moieties. Arabinose 1-->4 linkages and mannose 1-->2 linkages also exist in all
      strains. The only differences among these linkages are their monosaccharide
      compositions leading to different degree of backbone and branch formations.
      Cluster analyses of the GC-MS data of the exo-polysaccharides of the 10 strains
      resulted in 10 dendrograms. However, four of the 10 dendrograms were identical
      and were obtained using the average, Ward and weighted linkage type method of
      Manhattan distance and using the Ward method of Euclidean distance. The results
      of cluster analyses were not very much different from that of the AFLP assay and
      allowed the comparison of genetic and structural similarities and differences.

PMID- 17512820
TI  - On-line purge and trap gas chromatography for monitoring of trihalomethanes in
      drinking water distribution systems.
AB  - A method using an automated on-line purge and trap gas chromatograph with a dry
      electrolytic conductivity detector (DELCD) has been developed for monitoring four
      regulated trihalomethanes in drinking water distribution systems. This analyzer
      samples trihalomethanes from drinking water by pervaporation through a silicone
      capillary membrane contained within a gas extraction cell (GEC) followed by
      preconcentration using an adsorbent trap. Trihalomethanes are subsequently
      desorbed from the trap onto a capillary column, separated and detected. The
      analyzer operates in real-time, samples directly from the drinking water
      distribution system and is fully automated. The optimization, operation, and
      evaluation of the analyzer and method are discussed. Method detection limits
      (MDL) are less than 1.0 microg L(-1) with acceptable estimates for accuracy, and
      precision. The results from two on-line monitoring studies in chlorinated and
      chloraminated distribution systems are presented. The performance of the method
      is compared directly to United Stated Environmental Protection Agency Method
      502.2 and shows a very slight, but acceptable bias.

PMID- 17512821
TI  - A rapid quantitative method for humic substances determination in natural waters.
AB  - A simple and rapid method was proposed for humic substances (HS) determination at
      microgram levels in natural waters. This assay method is based on the binding of
      a dye, Toluidine Blue (TB), to HS molecules to produce a dye-HS complex, which
      causes a decrease in absorbance at 630 nm. This method was calibrated with HS
      samples with up to a concentration of 40 mg L(-1), which covered the range of
      dissolved HS concentrations present in natural waters. The detection limit was
      0.8 mg L(-1) of HS, and the relative standard deviation of 10 replicate
      measurements for a 20-mg L(-1) standard sample was 3.5%. From the Langmuir
      adsorption isotherm theory, the binding equilibrium constant and total number of
      binding sites at neutral pH were calculated to be (8.17+/-0.42)x10(5) L mol(-1)
      and N of 1.45+/-0.04 mmol g(-1) HS, respectively. The determination results with
      five water samples from lake, river and pond were consistent with those measured
      with the reference methods, demonstrating that this quantification method for HS
      determination was rapid, sensitive and feasible.

PMID- 17512822
TI  - Determination of ketotifen by using calcein as chemiluminescence reagent.
AB  - Chemiluminescence (CL) was observed when potassium hexacyanoferrate(III) reacted
      with the mixture of calcein and ketotifen. Interestingly, the CL intensity would
      be enhanced by trace amounts of Mg2+ and the CL intensity was strongly dependent
      on ketotifen concentration. Based on this phenomenon, a flow injection CL method
      was established for the determination of ketotifen. The possible CL mechanism is
      proposed based on the kinetic characteristic of the CL reaction, CL spectrum,
      ultraviolet (UV) spectra and fluorescent spectra. The CL intensity was correlated
      linearly with concentration of ketotifen over the range of 6.0x10(-9) to 2.0x10(
      7) g mL(-1) and the detection limit was 3x10(-9) g mL(-1). The relative standard
      deviation was 1.8% for 2.0x10(-8) g mL(-1) ketotifen (n=11). This method was
      applied to the determination of ketotifen in the tablets successfully.

PMID- 17512823
TI  - Flow-injection determination of zidovudine in plasma samples using multivariate
      curve resolution.
AB  - This paper describes a spectrophotometric flow-injection method for the
      determination of an antiretroviral drug (zidovudine) in plasma samples. The main
      goal of this study is the development of feasible analytical method to monitor
      the plasmatic drug levels in a rapid and simple way as an alternative to
      chromatographic procedures. The flow-injection system proposed consists of a two
      channel manifold with the injection of the sample into an acid carrier and on
      line generation of a pH-gradient. The corresponding data are monitored over time
      using a diode array spectrophotometer. The discrimination of zidovudine species
      from plasma components is accomplished through chemometric data analysis based on
      the zidovudine features on both spectral and time domains. A pretreatment
      procedure consisting of liquid-liquid extraction is used for sample clean-up.
      However, despite the pretreatment, noticeable amounts of unknown substances
      acting as interferences are still present in the extracts. As relevant analytical
      parameters, the analyte recovery in the extraction process is 101% at 5.3 microg
      mL(-1) and the detection limit is 0.013 microg mL(-1). Multivariate curve
      resolution with alternating least squares is used to recover the analyte profiles
      for its further determination. As a result, the quantification of zidovudine in
      plasma can be accomplished even in the presence of plasma components with overall
      prediction error below 3%.

PMID- 17512824
TI  - Estimation of performance characteristics of a confirmation method for
      thyreostats in plasma by means of a weighted least-squares approach.
AB  - A weighted linear regression-based approach was applied to ascertain analytical
      performance characteristics of a method for the quantitative determination of
      thyreostats in plasma by LC-MS. The weights were set equal to the reciprocal of
      the variances. A straightforward and practical procedure is presented that was
      used to model the variance of the replicate measurements as a function of
      concentration. Different function types were tested for their suitability.

PMID- 17512825
TI  - Determination of beta-lactam antibiotics in milk using micro-flow
      chemiluminescence system with on-line solid phase extraction.
AB  - In this paper, a chemiluminescence (CL) micro-flow system combined with on-line
      solid phase extraction (SPE) is presented for determination of beta-lactam
      antibiotics (penicillin, cefradine, cefadroxil, cefalexin) in milk. It is based
      on the enhancement effect of beta-lactam antibiotics on the luminol-K3Fe(CN)6 CL
      system. The micro-flow system was fabricated from two polymethyl methacrylate
      (PMMA) plates (50 mm x 40 mm x 5 mm) with the microchannels of 200 microm wide
      and 150 microm deep. C18-modified silica gel was packed into the microchannel
      (length: 10 mm; width: 1 mm; depth: 500 microm) to serve as SPE device.
      Extraction and preconcentration of the analytes were carried out using on-line
      SPE micro-flow system and the selectivity of CL detection was improved. The
      detection limits were 0.5 microg mL(-1) of penicillin, 0.04 microg mL(-1) of
      cefradine, 0.08 microg mL(-1) of cefadroxil and 0.1 microg mL(-1) of cefalexin.
      The proposed method was also applied to analyze the beta-lactam antibiotics in
      milk. Experimental results were in good agreement with those obtained by high
      performance liquid chromatography (HPLC) method with UV detection.

PMID- 17512826
TI  - Automatic flow system for sequential determination of ABTS*+ scavenging capacity
      and Folin-Ciocalteu index: a comparative study in food products.
AB  - In the present work, an automatic flow procedure for the sequential
      spectrophotometric determination of Folin-Ciocalteu reducing capacity (FC assay)
      and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS*+)
      scavenging capacity expressed as the trolox equivalent (TEAC assay) is proposed
      for a comparative study of antioxidant properties in food products. Exploiting
      the flexibility of flow management associated to the computer control offered by
      multisyringe flow injection analysis, both methodologies were carried out in the
      same manifold using gallic acid and trolox as standard compounds. The proposed
      system configuration allowed the performance of each method separately or in
      tandem, providing 24 determinations per hour, which accounts for its application
      in routine analysis. The present methodology was applied to a large number of
      beverages (n=72), namely red and white wines, herbal and tea infusions, juices
      and beers. The results obtained showed that FC reducing capacity and TEAC values
      of red wines were significantly different from those obtained for the other
      beverages, while tea infusions provided significantly higher TEAC values when
      compared to white wines, herbal infusions, juices and beers. A good correlation
      was found between TEAC and FC reducing capacity (R>0.9) for red wines, herbal and
      tea infusions, and beers. For these beverages, similar slope values were found
      (106-140 mg L(-1) of gallic acid per mM of Trolox), except for beers that showed
      a higher response for FC assay. These results provided evidence that the
      correlation between these assays vary according to the type of sample,
      reinforcing the idea that more than one method should be used for evaluation of
      antioxidant capacity.

PMID- 17512827
TI  - Enantiomeric quality control of antihistamines in pharmaceuticals by affinity
      electrokinetic chromatography with human serum albumin as chiral selector.
AB  - The present paper deals with the enantiomeric separation of six antihistaminic
      enantiomers by affinity electrokinetic chromatography (AEKC)-partial filling
      technique using human serum albumin (HSA) as chiral selector. A multivariate
      optimization approach of the most critical experimental variables in
      enantioresolution, running pH, HSA concentration and HSA plug length (SPL) was
      carried out since there are interactions between variables that could not be
      considered in an univariate optimization. The estimated and experimental
      resolution values obtained for antihistaminic enantiomers varied from 1.13 (for
      orphenadrine) to 2.15 (for brompheniramine). The optimum experimental conditions
      for enantioresolution of each compound were: brompheniramine, pH 8.5, [HSA] 180
      microM, SPL 180 s; chlorcyclizine, pH 6.5, [HSA] 180 microM, SPL 150 s;
      chlorpheniramine, pH 8.25, [HSA] 160 microM, SPL 150 s; hydroxyzine, pH 7.0,
      [HSA] 180 microM, SPL 150 s; and orphenadrine, pH 7.8, [HSA] 160 microM, SPL 150
      s. pH and the quadratic term of pH seem to be the most critical factors that
      determine enantioresolution of antihistamines. The validity of the developed
      methodologies to enantiomeric quality control of antihistamines in pharmaceutical
      formulations is demonstrated analyzing the content of brompheniramine,
      chlorpheniramine and hyroxyzine enantiomers in commercially available
      pharmaceutical formulations containing racemic mixtures of compounds. Resolution,
      accuracy, reproducibility, cost and sample throughput of the proposed
      methodologies make them suitable for quality control of the enantiomeric
      composition of antihistamines in pharmaceutical preparations.

PMID- 17512828
TI  - Assessing the statistical validity of proteomics based biomarkers.
AB  - A strategy is presented for the statistical validation of discrimination models
      in proteomics studies. Several existing tools are combined to form a solid
      statistical basis for biomarker discovery that should precede a biochemical
      validation of any biomarker. These tools consist of permutation tests, single and
      double cross-validation. The cross-validation steps can simply be combined with a
      new variable selection method, called rank products. The strategy is especially
      suited for the low-samples-to-variables-ratio (undersampling) case, as is often
      encountered in proteomics and metabolomics studies. As a classification method,
      principal component discriminant analysis is used; however, the methodology can
      be used with any classifier. A dataset containing serum samples from Gaucher
      patients and healthy controls serves as a test case. Double cross-validation
      shows that the sensitivity of the model is 89% and the specificity 90%. Potential
      putative biomarkers are identified using the novel variable selection method.
      Results from permutation tests support the choice of double cross-validation as
      the tool for determining error rates when the modelling procedure involves a
      tuneable parameter. This shows that even cross-validation does not guarantee
      unbiased results. The validation of discrimination models with a combination of
      permutation tests and double cross-validation helps to avoid erroneous results
      which may result from the undersampling.

PMID- 17512829
TI  - Estimation of non-ionic, surface-active substances in aqueous solutions by means
      of the Controlled Growth Mercury Electrode.
AB  - In this paper, a quick and simple tensammetric method of estimation of non-ionic
      surfactants (NS) in aqueous solutions is proposed. The method makes use of the
      variation in the differential capacity of double layer in relation to the time of
      accumulation (C(d)-t(acc)) of non-ionic surfactants at the hanging mercury drop
      electrode, generated by a single, very quick opening of the valve. Under such
      conditions, the capacity current measured at the potential of maximum adsorption
      diminishes with accumulation time of non-ionic surfactants. The proposed method,
      which was verified for model surfactant (Triton X-100), may also be applied in
      the determination of other NS. Modifications in construction of the CGME
      electrode and its improved metrological parameters played an important role in
      the presented procedure. In addition, other measurements were performed using
      standard electrochemical techniques, whereby current-time and differential
      capacity-potential curves were recorded. Satisfactory results were obtained in
      the determination of Triton X-100 in the range from 0.05 to 20 mg L(-1)
      (R.S.D.=6%, recovery=94-103%, r=0.999, DL=0.15 mg L(-1)). Applicability of the
      method was presented using the water samples from Bialka and Dunajec rivers, from
      which NS were removed by addition of fumed silica.

PMID- 17512832
TI  - Preventable errors in the operating room: retained foreign bodies after surgery-
      Part I.

PMID- 17512833
TI  - Cancer treatment: not just a question of costs.

PMID- 17512834
TI  - Stepping up child survival efforts.

PMID- 17512835
TI  - WHO signals strong commitment to evidence.

PMID- 17512836
TI  - Ovarian cancer and HRT in the Million Women Study.

PMID- 17512837
TI  - Ovarian suppression for early breast cancer.

PMID- 17512838
TI  - The risk of transmitting cancer with transfusion.

PMID- 17512839
TI  - Procedural simulation's developing role in medicine.

PMID- 17512842
TI  - Clinical update: immunosuppression minimisation.

PMID- 17512840
TI  - Medical training in the UK: sleepwalking to disaster.

PMID- 17512843
TI  - Jack Cuzick: working to improve cancer prevention and detection.

PMID- 17512844
TI  - Comparison of MTAS with the system in the USA.

PMID- 17512845
TI  - Collaboration between developed and developing nations.

PMID- 17512846
TI  - Global health and foreign policy.

PMID- 17512847
TI  - Global health and foreign policy.

PMID- 17512848
TI  - Global health and foreign policy.

PMID- 17512849
TI  - Undeclared motives in withdrawing a publication.

PMID- 17512850
TI  - Low-dose aspirin and small bowel enteropathy.

PMID- 17512851
TI  - Patients' behaviour in somatic illness.

PMID- 17512853
TI  - Belgium: historical champion in asbestos consumption.

PMID- 17512854
TI  - Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16,
      and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal
      lesions: a combined analysis of three randomised clinical trials.
AB  - BACKGROUND: Vulval and vaginal cancers among younger women are often related to
      infection with human papillomavirus (HPV). These cancers are preceded by high
      grade vulval intraepithelial neoplasia (VIN2-3) and vaginal intraepithelial
      neoplasia (VaIN2-3). Our aim was to do a combined analysis of three randomised
      clinical trials to assess the effect of a prophylactic quadrivalent HPV vaccine
      on the incidence of these diseases. METHODS: 18 174 women (16-26 years) were
      enrolled and randomised to receive either quadrivalent HPV6/11/16/18 L1 virus
      like-particle vaccine or placebo at day 1, and months 2 and 6. Individuals
      underwent detailed anogenital examination at day 1, 1 month after dose three, and
      at 6-12-month intervals for up to 48 months. Suspect genital lesions were
      biopsied and read by a panel of pathologists and vaccine HPV type-specific DNA
      testing was done. The primary endpoint was the combined incidence of VIN2-3 or
      VaIN2-3 associated with HPV16 or HPV18. Primary efficacy analyses were done in a
      per-protocol population. FINDINGS: The mean follow-up time was 3 years. Among
      women naive to HPV16 or HPV18 through 1 month after dose three (per-protocol
      population; vaccine n=7811; placebo n=7785), the vaccine was 100% effective (95%
      CI 72-100) against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. In the
      intention-to-treat population (which included 18 174 women who, at day 1, could
      have been infected with HPV16 or HPV18), vaccine efficacy against VIN2-3 or VaIN2
      3 associated with HPV16 or HPV18 was 71% (37-88). The vaccine was 49% (18-69)
      effective against all VIN2-3 or VaIN2-3, irrespective of whether or not HPV DNA
      was detected in the lesion. The most common treatment-related adverse event was
      injection-site pain. INTERPRETATION: Prophylactic administration of quadrivalent
      HPV vaccine was effective in preventing high-grade vulval and vaginal lesions
      associated with HPV16 or HPV18 infection in women who were naive to these types
      before vaccination. With time, such vaccination could result in reduced rates of
      HPV-related vulval and vaginal cancers.

PMID- 17512855
TI  - Ovarian cancer and hormone replacement therapy in the Million Women Study.
AB  - BACKGROUND: Ovarian cancer is the fourth most common cancer in women in the UK,
      with about 6700 developing the malignancy and 4600 dying from it every year.
      However, there is limited information about the risk of ovarian cancer associated
      with the use of hormone replacement therapy (HRT). METHODS: 948,576
      postmenopausal women from the UK Million Women Study who did not have previous
      cancer or bilateral oophorectomy were followed-up for an average of 5.3 years for
      incident ovarian cancer and 6.9 years for death. Information on HRT use was
      obtained at recruitment and updated where possible. Relative risks for ovarian
      cancer were calculated, stratified by age and hysterectomy status, and adjusted
      by area of residence, socioeconomic group, time since menopause, parity, body
      mass index, alcohol consumption, and use of oral contraceptives. FINDINGS: When
      they last reported HRT use, 287,143 women (30%) were current users and 186 751
      (20%) were past users. During follow-up, 2273 incident ovarian cancers and 1591
      deaths from the malignancy were recorded. Current users were significantly more
      likely to develop and die from ovarian cancer than never users (relative risk
      1.20 [95% CI 1.09-1.32; p=0.0002] for incident disease and 1.23 [1.09-1.38;
      p=0.0006] for death). For current users of HRT, incidence of ovarian cancer
      increased with increasing duration of use, but did not differ significantly by
      type of preparation used, its constituents, or mode of administration. Risks
      associated with HRT varied significantly according to tumour histology
      (p<0.0001), and in women with epithelial tumours the relative risk for current
      versus never use of HRT was greater for serous than for mucinous, endometroid, or
      clear cell tumours (1.53 [1.31-1.79], 0.72 [0.52-1.00], 1.05 [0.77-1.43], or 0.77
      [0.48-1.23], respectively). Past users of HRT were not at an increased risk of
      ovarian cancer (0.98 [0.88-1.11] and 0.97 [0.84-1.11], respectively, for incident
      and fatal disease). Over 5 years, the standardised incidence rates for ovarian
      cancer in current and never users of HRT were 2.6 (2.4-2.9) and 2.2 (2.1-2.3) per
      1000, respectively-ie, one extra ovarian cancer in roughly 2500 users; death
      rates were 1.6 (1.4-1.8) and 1.3 (1.2-1.4) per 1000, respectively-ie, one extra
      ovarian cancer death in roughly 3300 users. INTERPRETATION: Women who use HRT are
      at an increased risk of both incident and fatal ovarian cancer. Since 1991, use
      of HRT has resulted in some 1300 additional ovarian cancers and 1000 additional
      deaths from the malignancy in the UK.

PMID- 17512856
TI  - Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in
      premenopausal patients with hormone-receptor-positive breast cancer: a meta
      analysis of individual patient data from randomised adjuvant trials.
AB  - BACKGROUND: Several trials have been done to assess treatment of premenopausal
      breast cancer with luteinising-hormone-releasing hormone (LHRH) agonists, but
      results have been inconclusive, especially for patients with hormone-receptor
      positive cancer. METHODS: We collected individual patients' data from published
      trials and did analyses focused on women with tumours positive for oestrogen
      receptor, progesterone receptor, or both. The main endpoints were recurrence and
      death after recurrence. FINDINGS: We obtained data for 11 906 premenopausal women
      with early breast cancer randomised in 16 trials. When used as the only systemic
      adjuvant treatment, LHRH agonists did not significantly reduce recurrence (28.4%
      relative reduction, 95% CI consistent with 50.5% reduction to 3.5% increase,
      p=0.08) or death after recurrence (17.8%, 52.8% reduction to 42.9% increase,
      p=0.49) in hormone-receptor-positive cancers. Addition of LHRH agonists to
      tamoxifen, chemotherapy, or both reduced recurrence by 12.7% (2.4-21.9, p=0.02);
      and death after recurrence by 15.1% (1.8-26.7, p=0.03). LHRH agonists showed
      similar efficacy to chemotherapy (recurrence 3.9% increase, 7.7% reduction to
      17.0% increase; death after recurrence 6.7% reduction, 20.7% reduction to 9.6%
      increase; both not significant). No trials had assessed an LHRH agonist versus
      chemotherapy with tamoxifen in both arms. LHRH agonists were ineffective in
      hormone-receptor-negative tumours. INTERPRETATION: LHRH agonists provide an
      additional class of agents for treatment of premenopausal women with hormone
      receptor-positive breast cancer. Optimum duration of use is unknown.

PMID- 17512857
TI  - Risk of cancer after blood transfusion from donors with subclinical cancer: a
      retrospective cohort study.
AB  - BACKGROUND: Although mechanisms for detection of short-term complications after
      blood transfusions are well developed, complications with delayed onset, notably
      transmission of chronic diseases such as cancer, have been difficult to assess.
      Our aim was to investigate the possible risk of cancer transmission from blood
      donors to recipients through blood transfusion. METHODS: We did a register-based
      retrospective cohort study of cancer incidence among patients who received blood
      from donors deemed to have a subclinical cancer at the time of donation. These
      precancerous donors were diagnosed with a cancer within 5 years of the donation.
      Data from all computerised blood bank registers in Sweden and Denmark gathered
      between 1968 and 2002 were merged into a common database. Demographic and medical
      data, including mortality and cancer incidence, were ascertained through linkages
      with nationwide, and essentially complete, population and health-care registers.
      The risk of cancer in exposed recipients relative to that in recipients who
      received blood from non-cancerous donors was estimated with multivariate Poisson
      regression, adjusting for potential confounding factors. FINDINGS: Of the 354 094
      transfusion recipients eligible for this analysis, 12,012 (3%) were exposed to
      blood products from precancerous donors. There was no excess risk of cancer
      overall (adjusted relative risk 1.00, 95% CI 0.94-1.07) or in crude anatomical
      subsites among recipients of blood from precancerous donors compared with
      recipients of blood from non-cancerous donors. INTERPRETATION: Our data provide
      no evidence that blood transfusions from precancerous blood donors are associated
      with increased risk of cancer among recipients compared with transfusions from
      non-cancerous donors.

PMID- 17512858
TI  - Gastrointestinal stromal tumour.
AB  - Gastrointestinal stromal tumours are the most common mesenchymal neoplasm of the
      gastrointestinal tract and are highly resistant to conventional chemotherapy and
      radiotherapy. Such tumours usually have activating mutations in either KIT (75
      80%) or PDGFRA (5-10%), two closely related receptor tyrosine kinases. These
      mutations lead to ligand-independent activation and signal transduction mediated
      by constitutively activated KIT or PDGFRA. Targeting these activated proteins
      with imatinib mesylate, a small-molecule kinase inhibitor, has proven useful in
      the treatment of recurrent or metastatic gastrointestinal stromal tumours and is
      now being tested as an adjuvant or neoadjuvant. However, resistance to imatinib
      is a growing problem and other targeted therapeutics such as sunitinib are
      available. The important interplay between the molecular genetics of
      gastrontestinal stromal tumour and responses to targeted therapeutics serves as a
      model for the study of targeted therapies in other solid tumours.

PMID- 17512860
TI  - How to prevent 100 million deaths from tobacco.

PMID- 17512861
TI  - Radiotherapy and the heart.

PMID- 17512863
TI  - Images in emergency medicine. Ellis III and I tooth fractures.

PMID- 17512859
TI  - Metastasis: recent discoveries and novel treatment strategies.
AB  - Most cancer deaths are due to the development of metastases, hence the most
      important improvements in morbidity and mortality will result from prevention (or
      elimination) of such disseminated disease. Some would argue that treatments
      directed against metastasis are too late because cells have already escaped from
      the primary tumour. Such an assertion runs contrary to the significant but (for
      many common adult cancers) fairly modest improvements in survival following the
      use of adjuvant radiation and chemotherapy designed to eliminate disseminated
      cells after surgical removal of the primary tumour. Nonetheless, the debate
      raises important issues concerning the accurate early identification of
      clonogenic, metastatic cells, the discovery of novel, tractable targets for
      therapy, and the monitoring of minimal residual disease. We focus on recent
      findings regarding intrinsic and extrinsic molecular mechanisms controlling
      metastasis that determine how, when, and where cancers metastasise, and their
      implications for patient management in the 21st century.

PMID- 17512862
TI  - Keys to successful management of patients with allergic rhinitis: focus on
      patient confidence, compliance, and satisfaction.
AB  - OBJECTIVE: The American Academy of Otolaryngic Allergy (AAOA) convened an expert,
      multidisciplinary Working Group on Allergic Rhinitis to discuss patients' self
      treatment behaviors and how health care providers approach and treat the
      condition. PROCEDURES AND DATA SOURCES: Co-moderators, who were chosen by the
      AAOA Board of Directors, were responsible for initial agenda development and
      selection of presenters and participants, based on their expertise in diagnosis
      and treatment of allergic rhinitis. Each presenter performed a literature search
      from which a presentation was developed, portions of which were utilized in
      developing this review article. SUMMARY OF FINDINGS: Allergic rhinitis is a
      common chronic condition that has a significant negative impact on general
      health, co-morbid illnesses, productivity, and quality of life. Treatment of
      allergic rhinitis includes avoidance of allergens, immunotherapy, and/or
      pharmacotherapy (ie, antihistamines, decongestants, corticosteroids, mast cell
      stabilizers, anti-leukotriene agents, anticholinergics). Despite abundant
      treatment options, 60% of all allergic rhinitis patients in an Asthma and Allergy
      Foundation of America survey responded that they are "very interested" in finding
      a new medication and 25% are "constantly" trying different medications to find
      one that "works." Those who were dissatisfied also said their health care
      provider does not understand their allergy treatment needs and does not take
      their allergy symptoms seriously. Dissatisfaction leads to decreased compliance
      and an increased reliance on multiple agents and over-the-counter products.
      Furthermore, a lack of effective communication between health care provider and
      patient leads to poor disease control, noncompliance, and unhappiness in a
      significant portion of patients. CONCLUSIONS: Health care providers must gain a
      greater understanding of patient expectations to increase medication compliance
      and patient satisfaction and confidence.

PMID- 17512864
TI  - Images in emergency medicine. Hemorrhagic pancreatitis.

PMID- 17512865
TI  - Images in emergency medicine. Boerhaave's syndrome (spontaneous esophageal
      rupture).

PMID- 17512866
TI  - Is hydroxocobalamin safe and effective for smoke inhalation? Searching for
      guidance in the haze.

PMID- 17512867
TI  - Commentary: What happens to crash victims after we resuscitate them?

PMID- 17512868
TI  - The pharmacist and me.

PMID- 17512869
TI  - Images in emergency medicine. Foreign body aspiration.

PMID- 17512870
TI  - Images in emergency medicine. Chlamydia conjunctivitis.

PMID- 17512871
TI  - Lack of pharmacokinetic information in children leads clinicians to use
      experience and trial-and-error to determine how best to administer ketamine.

PMID- 17512872
TI  - Hepatic rupture after Heimlich maneuver.

PMID- 17512874
TI  - Disclosing the errors of other physicians.

PMID- 17512876
TI  - Brugada electrocardiographic pattern induced by cocaine toxicity.

PMID- 17512878
TI  - Parents as teachers and evaluators of medical student professionalism.

PMID- 17512879
TI  - Parents who walk away.

PMID- 17512880
TI  - Use of unstructured parent narratives to evaluate medical student competencies in
      communication and professionalism.
AB  - OBJECTIVE: Medical education programs across the country are now required to
      conduct meaningful assessments of trainees' competencies, although uniform
      standards for conducting these evaluations have yet to be established. In 1999,
      the Indiana University School of Medicine introduced a comprehensive competency
      based undergraduate curriculum. The overall goal of the curriculum is to make
      medical students' day-to-day experiences of training a source of learning about
      professionalism, communication, and aspects of medicine beyond factual knowledge.
      We sought to examine free-text comments by parents of pediatric inpatients as
      substrate for competency evaluation and feedback for third-year students on their
      pediatrics rotation. METHODS: The study was conducted from June 2001 to February
      2004. Parents of hospitalized children completed a short medical student
      evaluation form that included 2 questions inviting free-text response. We used
      narrative analysis, a qualitative research technique, to describe both the
      content and meaning of the parents' responses. RESULTS: We collected 573
      evaluations with narrative comments about 412 students. The most common aspect of
      medical student performance commented on by parents related to communication
      (53.8%). The next most common narrative comment was some form of affirmation of
      the student as a health care professional (26.0%). Other themes included
      establishing context for the comment, perceptions of the health care system,
      criticizing medical student performance, perceptions of the role of medical
      students, physical approach to the patient, expression of humility by the
      student, holistic approach to the patient, physical appearance of the student,
      superlative description of student, and advocating for the patient. Multiple
      themes were identified in 232 narrative comments (40.4%). Examples of each theme
      are provided. CONCLUSIONS: Family members of pediatric inpatients are a valuable
      source of information about medical student performance in at least 2 of the
      Accreditation Council for Graduate Medical Education competency areas
      (Communication and Professionalism). Themes identified in this study could be
      used to inform the design of a comprehensive 360-degree student evaluation
      strategy.

PMID- 17512881
TI  - Learning about systems-based practice in the informal curriculum: a case study in
      an academic pediatric continuity clinic.
AB  - OBJECTIVE: Pediatric residents learn about systems-based practice (SBP)
      explicitly in the formal curriculum and implicitly in the informal curriculum as
      they engage in practice alongside physician faculty. Recent studies describe
      innovative ways to address SBP in the formal curriculum for SBP, but the informal
      curriculum has not been explored. We examined what, and how, third-year pediatric
      residents learn about SBP in the informal curriculum at one continuity clinic,
      and to consider how this learning aligns with the formal curriculum. METHODS: A
      case study involving 10 third-year pediatric residents and 10 continuity
      preceptors was conducted at one continuity clinic, housed in a community-based,
      pediatric primary care center. Data were derived from 5 months (100 hours) of
      direct observation in the precepting room at the case clinic, semistructured
      interviews with residents (before and after observation) and with preceptors
      (after observation). Interview transcripts and notes from observation were
      inductively coded and analyzed for major themes. RESULTS: Two themes emerged in
      the informal curriculum. Residents perceived "our system," the academic health
      system in which they trained and practiced as separate and distinct from the
      "real system," the larger, societal context of health care. Residents also
      understood SBP as a commitment to helping individual patients and families
      navigate the complexities of "our system," dealing with issues that concerned
      them. CONCLUSIONS: Residents learn important lessons about SBP in the informal
      curriculum in continuity clinic. These lessons may reinforce some elements of the
      competency-based formal curriculum for SBP, but challenge others.

PMID- 17512882
TI  - Student competence in fluid and electrolyte management: the impact of various
      teaching methods.
AB  - OBJECTIVE: The goal of this study was to evaluate 1) the competency of junior
      medical students (M3s) in fluid and electrolyte management upon completion of
      their pediatric clerkship; 2) the frequency and perceived helpfulness of fluid
      and electrolyte management-based interactions with the following sources of
      education: a lecture, first-year residents (PL1s), senior residents (PL3s), and
      faculty; and 3) the relationship between points 1 and 2. METHODS: Upon completion
      of the clerkship, M3 competency was evaluated by a quiz with multiple-choice
      questions and a clinical vignette concerning the intravenous fluid (IVF)
      management of a dehydrated child. Junior medical students completed a survey to
      identify the fluid and electrolyte management case-based practice frequency with
      PL1s, PL3s, and faculty, and the perceived helpfulness of the lecture, PL1s,
      PL3s, and faculty, rated on a 10-point Likert scale. RESULTS: One hundred eighty
      seven M3s took the quiz and 180 completed surveys. The mean clinical vignette
      score was 7.0 (range, 0-12). Eighty-one percent of M3s wrote inadequate IVF
      orders for a dehydrated infant. The median-perceived helpfulness for each source
      was lecture, 9 points; PL1, 5 points; PL3, 4 points; and faculty, 3 points. In
      multivariate regression, only a higher perceived helpfulness rating for the
      lecture was significantly associated with higher clinical vignette scores (r =
      0.43; P < .001). When asked for ideas to improve fluid and electrolyte management
      education, 47% of M3s recommended more practice problems. CONCLUSIONS: Most M3s
      lacked adequate fluid and electrolyte management competency. Junior medical
      students rated the lecture the most helpful source of fluid and electrolyte
      management education. Improvements in fluid and electrolyte management education
      of M3s may result from providing practice problems with immediate feedback and
      formal training to increase the fluid and electrolyte management educational
      skills of PL1s, PL3s, and faculty.

PMID- 17512883
TI  - Community perspectives of childhood behavioral problems and ADHD among African
      American parents.
AB  - OBJECTIVE: To explore parents' perceptions of childhood behavior problems and
      attention-deficit/hyperactivity disorder (ADHD) among a sample of African
      American (AA) parents. METHODS: Five focus groups were conducted in inner-city
      Baltimore and the Washington, DC, metropolitan region with 5 to 7 AA parents per
      group. Adults with children under the age of 17 years were recruited from
      pediatric practices. One investigator moderated each focus group, and a second
      took notes. Sessions averaged 1.5 hours long, were recorded on audiotape, and
      were transcribed verbatim. The narrative data were coded for recurring themes.
      RESULTS: Five major themes emerged from the analysis: causes of behavioral
      problems in children, the legitimacy of ADHD as a diagnosis, attitudes about
      doctors, opinions of medication, and perceptions of the school environment. Many
      participants felt that behavior issues, including those accompanying ADHD, were
      caused by inappropriate parenting and disciplinary practices. Some viewed the
      diagnosis as a label applied with racial inequality to exert social control over
      AAs. Several expressed distrust in physicians who were quick to make a diagnosis
      of ADHD and recommend medications. Others worried that medication would lead to
      drug addiction in adulthood. Some perceived that children were labeled with ADHD
      because of poor educational environments that were unresponsive to the needs of
      AA children. CONCLUSIONS: These focus groups identified important community
      perceptions about ADHD and its medical treatment. Understanding how these
      perceptions contribute to racial disparities in ADHD diagnosis and treatment can
      help inform culturally sensitive interventions to improve the management of ADHD
      among AA children.

PMID- 17512884
TI  - Media content and externalizing behaviors in Latino toddlers.
AB  - OBJECTIVE: There has been limited study of the association between media exposure
      and behavior in children younger than age 3 years. We sought to study this
      association in toddlers and determine whether the association varied depending on
      media content. METHODS: We carried out a secondary analysis of a cohort of Latino
      mother-infant dyads followed from birth to 33 months. We assessed media exposure
      at 21 and 33 months with a 24-hour recall diary that included information about
      the duration and content of each program watched. Behavior was assessed at 33
      months by the Child Behavior Checklist. RESULTS: This analysis included 99 dyads.
      Results from multiple logistic regression analyses indicated associations of
      child behavior outcomes with 21-month total media exposure and both 21-month and
      33-month exposure to noneducational young child media such as cartoons, after
      adjusting for maternal education, country of origin, and depressive symptoms,
      participation in a parenting program, and difficult child temperament. Media
      exposure has most consistent associations with aggressive behavior and
      externalizing problems. CONCLUSIONS: Media exposure was associated with
      externalizing behavior in Latino toddlers, with the strongest association for
      media oriented toward young children but without educational content. This
      finding has importance for both parents of young children and pediatricians as
      they provide anticipatory guidance.

PMID- 17512885
TI  - In the moment: attitudinal measure of pediatrician management of maternal
      depression.
AB  - OBJECTIVE: Pediatricians are in a good position to identify women who struggle
      with depression, but studies show low rates of pediatrician identification and
      management. It is likely that pediatricians' management of maternal depression
      may vary on the basis of their attitudes, but no instrument has been developed to
      measure these attitudes. We sought to develop a measure of pediatricians'
      attitudes about managing maternal depression and to identify characteristics
      associated with pediatricians' attitudes about managing maternal depression.
      METHODS: We conducted a cross-sectional analysis of data provided by 651
      practicing, nontrainee pediatricians (response rate 57.5%) surveyed through an
      American Academy of Pediatrics 2004 Periodic Survey. An exploratory principal
      components analysis was used to investigate the interrelationships among the
      attitudinal items. Multivariable linear regression was used to assess the
      adjusted associations between physician and practice characteristics and
      attitudes. RESULTS: The attitudinal measure consisted of 3 subscales:
      acknowledging maternal depression, perceptions of mothers' beliefs, and treating
      maternal depression. Clinical approaches (eg, interest in further education on
      identifying or treating maternal depression) and training and work
      characteristics were significantly related to pediatricians' attitudes; patient
      characteristics (eg, type of insurance and ethnicity/race) were not significantly
      associated with pediatricians' attitudes. CONCLUSIONS: We developed a measure to
      assess pediatricians' attitudes about managing maternal depression. The findings
      from this study can be used to develop and assess interventions that improve
      pediatricians' attitudes about acknowledging maternal depression, perceptions of
      mothers' beliefs, and treating maternal depression.

PMID- 17512886
TI  - Community engagement in epidemiological research.
AB  - OBJECTIVE: Engaging communities has become a critical aspect of planning and
      implementing health research. The role community engagement should play in
      epidemiological and observational research remains unclear since much of this
      research is not directly generated by community concerns and is not
      interventional in nature. The National Children's Study (NCS), an observational
      longitudinal study of 100,000 children and their families, provides a model to
      help guide the development of community engagement strategies in epidemiologic
      research. METHODOLOGY: This manuscript describes community engagement activities
      of the NCS during the planning phases of the study. RESULTS: There are many
      challenges of community engagement in epidemiologic research particularly before
      the actual research sites are determined. After communities of interest are
      designated many further issues must be resolved, including: defining the specific
      community, determining which residents or institutions represent the identified
      community, and developing trust and rapport through respectful engagement.
      CONCLUSIONS: Community engagement is critical to the long-term success of any
      longitudinal epidemiologic study. A partnership with the community should be
      formed to ensure mutual respect and the establishment of an enduring
      relationship. Genuine community engagement offers the hope of enhancing
      recruitment, retention, and participant satisfaction.

PMID- 17512887
TI  - Bullying among children with autism and the influence of comorbidity with ADHD: a
      population-based study.
AB  - OBJECTIVE: Bullying is a significant problem among school-age children. The
      prevalence and predictors of bullying among children with autism are not known.
      The objectives of this population-based study were to: (1) estimate the
      prevalence of bullying among children with autism in the United States, (2)
      determine whether the presence of attention-deficit/hyperactivity
      disorder/attention-deficit disorder (ADHD/ADD) increases prevalence of bullying
      among children with autism, and (3) determine risk factors of bullying behavior
      among children with autism. METHODS: The National Survey of Children's Health,
      2003 (NSCH), provided nationally representative data for children ages 4 to 17.
      We used multivariate logistic regression and Wald tests to determine whether
      children with autism were more likely to bully in the presence of ADHD/ADD.
      Taylor approximations were used to account for the complex sampling design.
      RESULTS: Children with autism had a high prevalence of bullying (44%, 95%
      confidence interval, 34-55). Parent report of ADHD/ADD appears to moderate the
      relationship between bullying and autism. Children with autism who did not have
      ADHD/ADD were not at greater risk for bullying compared with the general
      population. Children with autism and ADHD/ADD had increased odds of bullying
      (odds ratio 4.6, 95% confidence interval 2.4-8.6), even after controlling for
      household income, age, and gender. In addition to ADHD/ADD, living in a low
      income household and younger age were risk factors for bullying among children
      with autism. Being female, however, did not decrease the risk of bullying in the
      autistic subpopulation. CONCLUSIONS: Children with autism and ADHD/ADD appear to
      be at increased risk for bullying behaviors.

PMID- 17512888
TI  - Relationship between social inequalities and ambulatory care-sensitive
      hospitalizations persists for up to 9 years among children born in a major
      Canadian urban center.
AB  - OBJECTIVE: Hospitalizations for ambulatory care-sensitive (ACS) conditions have
      been considered a marker for access to timely and effective primary care, but
      there are few pediatric studies. Our purpose was to examine socioeconomic
      disparities in ACS and non-ACS admissions among birth cohorts in a universal
      health insurance setting. METHODS: We examined ACS and all hospitalizations of
      children born from 1993 to 2000 in Toronto, Canada, by birth year, calendar year,
      and socioeconomic status (SES). SES was evaluated by using quintiles of mean
      neighborhood income from the 1996 Canadian census. Cohort, age, and temporal
      effects were described for all admissions, ACS admissions, and specific ACS
      conditions. Attributable risk by SES was calculated by using rates for the
      highest and lowest SES quintiles. RESULTS: Among 255,284 children born in Toronto
      during 1993-2001, ACS conditions were responsible for 28% of hospitalizations
      during the first 2 years of life and close to half of admissions during the third
      year. Low income was associated with 50% higher rates of ACS hospitalizations
      (relative risk [RR] = 1.50, 95% confidence interval [95% CI] 1.43-1.58),
      including asthma (RR = 1.69, 95% CI 1.54-1.86) and bacterial pneumonia (RR =
      1.59, 95% CI 1.40-1.81), the leading causes of admission. Socioeconomic
      disparities in ACS and all admissions occurred in every cohort, every calendar
      year, and every age group. CONCLUSIONS: The relationship between socioeconomic
      disadvantage and both ACS and all-cause hospitalization in children was large,
      consistent across many conditions, remained stable over time, and persisted up to
      9 years of age. These effects occurred in a universal health insurance setting
      without direct financial barriers to physician or hospital care. The effect of
      SES on hospitalizations in children in our setting appears to be mediated by
      factors other than financial access to care.

PMID- 17512889
TI  - Hospitalizations for ambulatory care-sensitive conditions: where do we go from
      here?

PMID- 17512890
TI  - A homogeneous assay to measure live and dead cells in the same sample by
      detecting different protease markers.
AB  - A method to simultaneously determine the relative numbers of live and dead cells
      in culture by introducing a combination of two fluorogenic substrates or a
      fluorogenic and a luminogenic protease substrate into the sample is described.
      The method is based on detection of differential ubiquitous proteolytic
      activities associated with intact viable cells and cells that have lost membrane
      integrity. A cell-permeable peptide aminofluorocoumarin substrate detects
      protease activity restricted to intact viable cells. Upon cell death, the viable
      cell protease marker becomes inactive. An impermeable peptide rhodamine 110 (or
      aminoluciferin) conjugated substrate detects protease activity from nonviable
      cells that have lost membrane integrity. The multiplex assay can detect 200 dead
      cells in a population of 10,000 viable cells. The protease substrate reagents do
      not damage viable cells over the course of the assay, thus the method can be
      multiplexed further with other assays in a homogeneous format. Ratiometric
      measurement of viable and dead cells in the same sample provides an internal
      control that can be used to normalize data from other cell-based assays.

PMID- 17512891
TI  - Assessment of cellular actin dynamics by measurement of fluorescence anisotropy.
AB  - To study cellular actin dynamics, a cell-free assay based on fluorescence
      anisotropy was developed. Using G-actin-Alexa as a probe, we found that
      anisotropy enhancement reflects F-actin elongation. Anisotropy enhancement varies
      with the concentration of magnesium and calcium cations and with
      ethylenediaminetetraacetate or well-known effectors of the polymerization. This
      assay gives the overall status of actin dynamics in cell extracts which are the
      closest conditions to in vivo, implying most of the regulating proteins that are
      missing in purified actin measurements. It can be used in a large-scale screening
      for chemical compounds which modulate actin polymerization.

PMID- 17512893
TI  - Prolactinoma surgery.
AB  - Surgery is generally used as second-line treatment in prolactinomas. For
      microprolactinomas, it may be indicated in cases of resistance or intolerance to
      dopamine agonists or where patients prefer definitive cure to lifelong drug
      treatment. In highly trained hands, selective adenomectomy results in
      normalization of prolactin levels in 75-90% of cases with little morbidity and no
      mortality. However, subsequent relapse is possible in up to 20% of cases. In
      macroprolactinoma, a definitive cure is unlikely due to the frequency of invasive
      tumor extension. A transsphenoidal or, less frequently, a transfrontal surgical
      approach is necessary in patients resistant to or intolerant of medical
      treatment, and also in rare cases such as pituitary apoplexy or cerebrospinal
      fluid rhinorrhea.

PMID- 17512892
TI  - [Susceptibility markers in Tunisian first-degree relatives of patients with type
      1 diabetes].
AB  - To identify the profile of anti-pancreas autoantibodies and elucidate the HLA
      DRB1, DQB1 polymorphism in Tunisian first-degree relatives of patients with type
      1 diabetes, we recruited 96 relatives from 21 families with at least one diabetic
      child. Islet cell antibodies (ICA) were detected by immunofluorescence on monkey
      pancreas; glutamate decarboxylase (GADA), IA2 (IA2-A) and insulin (IAA)
      antibodies were measured by RIA. HLA class II DRB1 and DQB1 alleles were typed by
      PCR-SSP. ICA, GADA, IA2-A and IAA were found in respectively 11.5, 4.2, 5.2 and
      8.3% of relatives. Twenty-two out of 96 had at least one antibody and 20 out of
      these 22 had a susceptibility allele (DRB1*03, DRB1*04, DQB1*02 or DQB1*0302)
      with or without protective allele (DRB1*11, DRB1*13, DRB1*15 or DQB1*06). All of
      the 5 relatives having 2 autoantibodies or more carried the DRB1*04-DQB1*0302
      susceptible haplotype. In conclusion, this observational study confirms in a
      Tunisian population known epidemiological data and demonstrates the usefulness of
      follow-up to determine the predictive value of studied markers.

PMID- 17512894
TI  - [Recent advances in familial hypercholesterolemia].

PMID- 17512895
TI  - Radiotherapy of pituitary adenomas: state of the art.
AB  - Pituitary adenomas represent approximately 12% of intracranial tumors. They are
      defined as tumors that are functional or nonfunctional and invasive or
      noninvasive. Therapeutic strategies rely on surgery, medical treatment, and
      radiotherapy depending on histology. Neither the role of external radiotherapy
      nor the technique to be used are firmly established. Nonfunctioning adenomas must
      be operated on to relieve the compression. Prolactin-secreting adenomas are first
      treated with dopamine agonists, and GH-secreting adenomas are first treated by
      surgery if excising the complete tumor is possible; otherwise medical treatment
      is started. The first-line treatment of ACTH-secreting adenomas is surgery;
      however, in many cases, insufficient control of either secretion or tumoral
      volume leads to consideration of irradiation. Complications of conventional
      radiotherapy are well known and fractionated stereotactic radiotherapy appears to
      be as safe as radiosurgery. The volume to irradiate is still difficult to define,
      and this parameter can influence the technique chosen for treatment. Because the
      indications of radiotherapy are still debated, irradiation of pituitary adenomas
      must be decided by the complete team of endocrinologists, neurosurgeons,
      radiologists and radiotherapists.

PMID- 17512896
TI  - Smear layer and surface state affect dentin fluoride uptake.
AB  - OBJECTIVES: Polishing generates a smear layer (SL) on in vitro dentin samples
      that may influence fluoride uptake. We tested two hypotheses: SL increases
      fluoride uptake in superficial dentin (H1) and decreases fluoride uptake in
      deeper layers (H2) irrespectively of the amount of fluoride administered.
      METHODS: Polished bovine dentin with SL present and removed by four methods (5%
      tannic acid, 20s [TA]; 17% EDTA, 120 s; 38% phosphoric acid, 60s [PA]; and 10s
      air polishing) was fluoridated with 1200 or 12000 ppm F (NaF) solution (pH 4.0).
      RESULTS: Scanning electron microscopy (SEM) revealed that aggressiveness of SL
      removal varied by method from leaving SL patches behind (TA) to collagen exposure
      (PA). SL increased KOH-soluble and structurally bound fluoride uptake into
      superficial and deeper layers compared to SL free surfaces (except PA) following
      1200 ppm, but not 12000 ppm fluoridation. CONCLUSION: Presence of SL and surface
      conditions influence dentin fluoride uptake depending on fluoride concentration
      administered.

PMID- 17512897
TI  - Modeling P2Y receptor-Ca2+ response coupling in taste cells.
AB  - Here we elaborated an analytical approach for the simulation of dose-response
      curves mediated by cellular receptors coupled to PLC and Ca(2+) mobilization.
      Based on a mathematical model of purinergic Ca(2+) signaling in taste cells, the
      analysis of taste cells responsiveness to nucleotides was carried out.
      Consistently with the expression of P2Y(2) and P2Y(4) receptors in taste cells,
      saturating ATP and UTP equipotently mobilized intracellular Ca(2+). Cellular
      responses versus concentration of BzATP, a P2Y(2) agonist and a P2Y(4)
      antagonist, implicated high and low affinity BzATP receptors. Suramin modified
      the BzATP dose-response curve in a manner that suggested the low affinity
      receptor to be weakly sensitive to this P2Y antagonist. Given that solely P2Y(2)
      and P2Y(11) are BzATP receptors, their high sensitivity to suramin is poorly
      consistent with the suramin effects on BzATP responses. We simulated a variety of
      dose-response curves for different P2Y receptor sets and found that the
      appropriate fit of the overall pharmacological data was achievable only with
      dimeric receptors modeled as P2Y(2)/P2Y(4) homo- and heterodimers. Our
      computations and analytical analysis of experimental dose-response curves raise
      the possibility that ATP responsiveness of mouse taste cells is mediated by
      P2Y(2) and P2Y(4) receptors operative mostly in the dimeric form.

PMID- 17512898
TI  - Treatment outcome of female agoraphobics 3-9 years after exposure in vivo: a
      comparison with healthy controls.
AB  - It is well documented that most agoraphobics, with or without panic disorder,
      respond to exposure in vivo. But only little data compared their anxiety levels
      at follow-up (FU) with those of healthy controls. Forty-two female agoraphobics
      with or without panic disorder participated in FUs 3-9 years after exposure in
      vivo. Agoraphobic symptoms were compared to data of 42 healthy controls, who were
      matched according to gender, age, marital and occupational status. Remission
      criteria were defined from agoraphobia scores of the controls. A total of 17
      (40%) of the patients had no further agoraphobic symptoms at all. A total of 15
      (36%) patients still had mild-to-moderate agoraphobic symptoms at FU. A total of
      10 (24%) were non-responders and suffered from severe agoraphobia at FU. The
      percentage of treated patients with complete remission is much higher than
      previously reported. However, the majority still suffer from mild or severe
      agoraphobic symptoms and could possibly benefit from additional interventions.

PMID- 17512899
TI  - Fluid shear stress enhances the sphingosine 1-phosphate responses in cell-cell
      interactions between platelets and endothelial cells.
AB  - Fluid shear stress modulates the functional responses of platelets and vascular
      cells, and plays an important role in the pathogenesis of vascular disorders,
      including atherosclerosis and restenosis. Since shear stress induces activation
      of platelets, which abundantly store sphingosine 1-phosphate (Sph-1-P), and
      upregulates the mRNA expression of S1P(1), the most important Sph-1-P receptor
      expressed on the endothelial cells, we examined the effects of shear stress on
      the Sph-1-P-related responses involving these cells. Shear stress was found to
      induce Sph-1-P release from the platelets in a shear intensity- and time
      dependent manner. Inhibitors of protein kinase C suppressed this mechanical force
      induced Sph-1-P release, suggesting involvement of this kinase. On the other
      hand, in vascular endothelial cells, shear stress increased S1P(1) protein
      expression, as revealed by flow-cytometric analysis, and the responsiveness to
      Sph-1-P, which was assessed by monitoring the intracellular Ca(2+) concentration.
      These results indicate that shear stress enhances the Sph-1-P responses in cell
      cell interactions between platelets and endothelial cells.

PMID- 17512900
TI  - The mechanism of action of nitric oxide-donating aspirin.
AB  - NO-donating aspirin (NO-ASA) is a promising anticancer drug. We studied the
      contribution of NO-ASA's components (ASA, NO-releasing moiety, and spacer linking
      them) to its effect. The ASA and NO-releasing moieties play no biological role:
      ASA inhibits the growth of colon cancer cells >100-fold less potently that NO
      ASA; and denitrated NO-ASA plus the NO-donor SNAP releasing the same amount of NO
      as NO-ASA, inhibit the growth of cancer cells >50-fold less potently than NO-ASA.
      The biologically active moiety of NO-ASA is the spacer: it is chemically reactive
      (studies with NO-ASA radiolabeled at the spacer demonstrated that it binds to
      proteins); and compounds in which the ASA or the NO-releasing groups are replaced
      inhibit cell growth similar to NO-ASA. We propose a mechanism of action of NO-ASA
      involving formation of quinone methide from its para and ortho isomers and of a
      carbocation from the meta, with the NO-releasing group functioning as a leaving
      group.

PMID- 17512901
TI  - Cooperative binding of TIA-1 and U1 snRNP in K-SAM exon splicing activation.
AB  - In 293 cells, splicing of the human fibroblast growth factor receptor-2 K-SAM
      alternative exon is inefficient, but can be made efficient by provoking TIA-1
      binding to the U-rich IAS1 sequence downstream from the exon's 5' splice site. We
      show here that TIA-1 domains known to interact with U1 snRNP and to recruit it to
      5' splice sites in vitro are required for TIA-1 activation of K-SAM exon splicing
      in vivo. We further show that tethering downstream from the K-SAM exon a fusion
      between the U1 snRNP component U1C and the bacteriophage MS2 coat protein
      provokes IAS1-dependent exon splicing, and present evidence that the fusion
      functions after its incorporation into U1 snRNP. Our in vivo data, taken together
      with previous in vitro results, show that K-SAM splicing activation involves
      cooperative binding of TIA-1 and U1 snRNP to the exon's 5' splice site region.

PMID- 17512902
TI  - Chitosan oligosaccharide (COS) inhibits LPS-induced inflammatory effects in RAW
      264.7 macrophage cells.
AB  - The focus of this study was to clarify the relation between the nitric oxide (NO)
      production and cytokine expression including tumor necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6), and also investigated the effect of COS on LPS
      stimuli from RAW 264.7 cell. The lipopolysaccharide (LPS) of Gram-negative
      bacteria induces the expression of cytokines and potent inducers of inflammatory
      cytokines such as TNF-alpha and IL-6. In this experiment, upon stimulation with
      increasing concentrations of chitosan, the LPS-stimulated TNF-alpha and IL-6
      secretion was significantly recovered within the incubation media of RAW 264.7
      cells. Consistently, RT-PCR with mRNA and Western blot with anti-cytokine
      antiserum including TNF-alpha and IL-6 showed that the amount of TNF-alpha and IL
      6 secretion in the incubation media recovered with the concentration of chitosan.
      The LPS-stimulated NO secretion was significantly recovered within the 6h and 12h
      incubation media of RAW 264.7 cells, too. The recovery effect of chitosan on IL-6
      and NO secretion may be induced via the stimulus of TNF-alpha in RAW 264.7 cell.
      These results once again suggest that chitosan oligosaccharide may have the anti
      inflammatory effect via the stimulus of TNF-alpha in the LPS-stimulated
      inflammation in RAW 264.7 cells.

PMID- 17512903
TI  - Serine/Threonine kinase dependent transcription from the polyhedrin promoter of
      SpltNPV-I.
AB  - Polyhedrin (polh) and p10 are the two hyper-expressed very late genes of
      nucleopolyhedroviruses. Alpha amanitin resistant transcription from Spodoptera
      litura nucleopolyhedrovirus (SpltNPV-I) polyhedrin promoter was observed with
      virus infected nuclear extract of NIV-HA-197 cells but not with that from
      uninfected nuclear extract. Anti-protein kinase-1 (pk1) antibody inhibited the
      transcription and the inhibition reversed on addition of pk1, however, pk1 mutant
      protein, K50M having no phosphorylation activity did not overcome the
      transcription inhibition. Chromatin immuno-precipitation assays with viral anti
      pk1 antibody showed the interaction of pk1 with the polh while electrophoretic
      mobility shift assays indicated the strong binding affinity (K(d) approximately
      5.5x10(-11)) of purified pk1 with the polh promoter. These results suggested that
      the viral coded pk1 acts as a transcription factor in transcribing baculovirus
      very late genes.

PMID- 17512904
TI  - Up-regulation of gastric cancer cell invasion by Twist is accompanied by N
      cadherin and fibronectin expression.
AB  - Twist, a newly found EMT-inducer, has been reported to be up-regulated in those
      of diffuse-type gastric carcinomas with high N-cadherin level. We show here
      MKN45, a cell line derived from undifferentiated carcinomas cells, expresses high
      levels of Twist. Down-regulation of Twist, using an antisense Twist vector in
      MKN45 cells, inhibits cell migration and invasion, companied with a morphologic
      changes associated with MET. Suppression of Twist also decreases the expressions
      of N-cadherin and fibronectin, but not of E-cadherin in MKN45. In contrast,
      overexpression of Twist in MKN28, a cell line derived from moderate
      differentiated carcinomas, results in up-regulation of N-cadherin and
      fibronectin, companied with down-regulation of E-cadherin. Taken together, our
      results suggest that Twist regulates cell motility and invasion in gastric cancer
      cell lines, probably through the N-cadherin and fibronectin production.

PMID- 17512905
TI  - A rapid assay for drug sensitivity of glioblastoma stem cells.
AB  - Glioblastoma (GBM) is a highly infiltrating, aggressive brain cancer with no
      available curative treatment. We developed a rapid assay for assessing the effect
      of various drugs on GBM stem cells. The assay uses a small number of separated
      CD133+ cells (20,000 in 0.2 ml) in 96-well plate that form neurospheres within 1
      2 days. Various drugs disperse the neurospheres within 24-36 h, which can be
      quantified microscopically. We used the GBM cell line A-172 to develop the
      conditions for the assay, utilizing Gleevec, the gamma-secretase inhibitor DAPT,
      and the anti-bacterial peptide amph1D. The results show dispersion of the
      neurospheres leading to cell death, at relatively low drugs concentrations (<25
      microM). Drug combination showed a synergistic effect and disruption of
      neurospheres under lower concentrations. We applied this assay to the CD133+
      cells of surgical specimens from three patients that showed similar results. This
      assay facilitates a rapid test of drugs on small amounts of fractionated
      patient's GBM stem cells.

PMID- 17512906
TI  - Human NIMA-related kinase 6 is one of the Fe65 WW domain binding proteins.
AB  - The Aspergillus nidulans protein NIMA (never in mitosis, gene A) is a protein
      kinase required for initiation of mitosis, whereas its inactivation is necessary
      for mitotic exit. Here, we present evidence that human Nek6 is associated with
      Fe65. Based on the presence of Fe65 WW domain binding motifs ((267)PPLP(270)) in
      the Nek6 catalytic domain, we observed that Nek6 interacts physically with Fe65
      both in vivo and in vitro, using a pull-down approach. Additionally, we detected
      co-localization of Nek6 and Fe65 via confocal microscopy. Co-localization of Nek6
      and Fe65 was disrupted by mutation of the WW domain binding motifs
      ((267)PPLP(270)). Finally, when transient transfection assays were performed,
      interaction of Nek6 (wt) with Fe65 induced substantial cell apoptosis, whereas
      interaction using the Nek6 pplp mutant ((267)PPLP(270) changes (267)APVA(270))
      did not. Thus, our observations indicated that Nek6 binds to Fe65 through its
      (267)PPLP(270) motif and that the protein-protein interaction between Nek6 and
      Fe65 regulates their subcellular localization and cell apoptosis.

PMID- 17512907
TI  - Functional characterization of Hsp33 protein from Bacillus
      psychrosaccharolyticus; additional function of HSP33 on resistance to solvent
      stress.
AB  - Psychrophiles have been known as efficient organism to degrade organic solvent.
      To investigate the mechanism of solvent stress and identify the factors that
      affect the solvent stress in psychrophiles, we selected Bacillus
      psychrosaccharolyticus one of the psychrophiles and two-dimensional gel
      electrophoresis was performed. Among the protein spots analyzed by 2-DE, five
      spots induced in 3% IPA stress conditions were identified by MS/MS, and one of
      these spots was identified as a Hsp33 family. The Hsp33 protein sequence of B.
      psychrosaccharolyticus exhibited a high similarity with the corresponding
      proteins of other bacteria. The Hsp33 protein of B. psychrosaccharolyticus has a
      highly conserved zinc-binding domain (CXCX, CXXC) that includes four cysteine
      residues in the C-terminus. In addition, the transcriptional induction of the
      HSP33 of B. psychrosaccharolyticus was confirmed by Northern blot analysis, and
      formation of free thiol linkage was induced under stress conditions such as
      exposure to solvents, heat-shock, and oxidative stress. Furthermore, over
      expressed strains of HSP33 of B. psychrosaccharolyticus in Escherichia coli
      improved stress tolerance to the organic solvent when compared with the wild
      type. These data suggest that the solvent stress condition was similar to heat
      shock or oxidative stress, especially through the triggering of induction and
      activation of a redox-regulatory chaperone, Hsp33, and Hsp33 plays a critical
      role in the tolerance to stress.

PMID- 17512908
TI  - Parent-of-origin dependent gene-specific knock down in mouse embryos.
AB  - In mice hemizygous for the Oct4-GFP transgene, the F1 embryos show parent-of
      origin dependent expression of the marker gene. F1 embryos with a maternally
      derived OG2 allele (OG2(mat)/-) express GFP in the oocyte and during
      preimplantation development until the blastocyst stage indicating a maternal and
      embryonic expression pattern. F1-embryos with a paternally inherited OG2 allele
      (OG2(pat)/-) express GFP from the 4- to 8-cell stage onwards showing only
      embryonic expression. This allows to study allele specific knock down of GFP
      expression. RNA interference (RNAi) was highly efficient in embryos with the
      paternally inherited GFP allele, whereas embryos with the maternally inherited
      GFP allele showed a delayed and less stringent suppression, indicating that the
      initial levels of the target transcript and the half life of the protein affect
      RNAi efficacy. RT-PCR analysis revealed only minimum of GFP mRNA. These results
      have implications for studies of gene silencing in mammalian embryos.

PMID- 17512909
TI  - Establishment of three-dimensional cultures of human pancreatic duct epithelial
      cells.
AB  - Three-dimensional (3D) cultures of epithelial cells offer singular advantages for
      studies of morphogenesis or the role of cancer genes in oncogenesis. In this
      study, as part of establishing a 3D culture system of pancreatic duct epithelial
      cells, we compared human pancreatic duct epithelial cells (HPDE-E6E7) with
      pancreatic cancer cell lines. Our results show, that in contrast to cancer cells,
      HPDE-E6E7 organized into spheroids with what appeared to be apical and basal
      membranes and a luminal space. Immunostaining experiments indicated that protein
      kinase Akt was phosphorylated (Ser473) and CTMP, a negative Akt regulator, was
      expressed in both HPDE-E6E7 and cancer cells. However, a nuclear pool of CTMP was
      detectable in HPDE-E6E7 cells that showed a dynamic concentrated expression
      pattern, a feature that further distinguished HPDE-E637 cells from cancer cells.
      Collectively, these data suggest that 3D cultures of HPDE-E6E7 cells are useful
      for investigating signaling and morphological abnormalities in pancreatic cancer
      cells.

PMID- 17512910
TI  - Ultrastructure of blood-brain barrier and blood-spinal cord barrier in SOD1 mice
      modeling ALS.
AB  - The purpose of this study was to determine the ultrastructure of the blood-brain
      barrier (BBB) and blood-spinal cord barrier (BSCB) in G93A SOD1 mice modeling ALS
      at different stages of disease. Electron microscope examination of brainstem,
      cervical and lumbar spinal cords was performed in ALS mice at early and late
      stages of disease. Our results show disorganized mitochondrial cristae and
      degenerating mitochondria in endothelial cells and neuropil, swollen astrocyte
      foot processes, swollen and degenerating capillary endothelial cells, astrocytes
      and motor neurons and extensive extracellular edema. In spite of progressive
      extracellular edema in neural tissue, capillary endothelial cell tight junctions
      appeared to remain intact in early and late symptomatic animals. Results show
      that disruption of BBB and BSCB was evident in areas of motor neuron degeneration
      in G93A mice at both early and late stages of disease. Capillary rupture was
      observed in brainstem in early symptomatic G93A mice. Capillary ultrastructure
      revealed that endothelial cell membrane and/or basement membrane damage occurred,
      followed by vascular leakage.

PMID- 17512911
TI  - Presynaptic adenosine A1 receptors modulate excitatory synaptic transmission in
      the posterior piriform cortex in rats.
AB  - The effect of adenosine on the fEPSP was examined in the lateral olfactory tract
      (Ia input) and associative tract (Ib input) of the rat piriform cortex. The fEPSP
      evoked in the Ia input showed paired-pulse facilitation, while that in the Ib
      input showed paired-pulse depression, suggesting a lower resting release
      probability in the Ia input. This was supported by results showing that MK801
      blocked the NMDA receptor-induced fEPSP more rapidly in the Ib input than the Ia
      input. Adenosine caused dose-dependent inhibition of the fEPSP in both inputs,
      the sensitivity being higher in the Ib input. This effect was mimicked by the
      A(1) receptor agonist, CHA, and antagonized by co-application of the A(1)
      receptor antagonist, DPCPX, showing that adenosine was acting at A(1) receptors.
      Application of DPCPX alone caused an increase in the fEPSP, the increase being
      larger in the Ia input. DPCPX also caused paired-pulse depression in both inputs,
      and the paired-pulse ratio measured in its presence was very similar in both
      inputs. These results suggest there is a lower endogenous concentration of
      adenosine in the Ib sublayer than the Ia sublayer, which might account for the
      native difference in the resting release probability of the two inputs. The
      adenosine-induced inhibition of the fEPSP in both inputs was associated with a
      significant reduction in the rate at which MK801 blocked NMDA receptor-mediated
      fEPSP activity, suggesting a presynaptic location of the A(1) receptors. Blocking
      of N-, P/Q-type calcium channels occluded the inhibition by adenosine, indicating
      that they are downstream effectors of presynaptic A(1) receptor activation.

PMID- 17512912
TI  - Polyethylene glycol inhibits apoptotic cell death following traumatic spinal cord
      injury.
AB  - We have previously shown that local administration of polyethylene glycol (PEG,
      MW: 2000 Da, 50% by weight), a known membrane repair agent, immediately after
      trauma in guinea pig spinal cord repairs neuronal membrane disruptions and
      reduces oxidative injury. Here we report that a similar application of PEG
      resulted in marked decreases in apoptotic cell death and caspase-3 activity. We
      suggest that PEG may suppress apoptosis through interactions with mitochondria.
      This is based on our current findings that in isolated mitochondria, PEG improves
      mitochondrial function and reduces the release of cytochrome c, a pro-apoptotic
      cell death factor. This hypothesis is further supported by our previous
      observation that PEG enters injured cells after spinal cord injury, placing PEG
      in a position to directly interact with mitochondria. In summary, we conclude
      that PEG reduces both necrosis and apoptosis through two distinct yet synergistic
      pathways: repair of disrupted plasma membranes and protection of mitochondria
      through direct interaction.

PMID- 17512913
TI  - Brain-derived neurotrophic factor-immunoreactive neurons in the rat vagal and
      glossopharyngeal sensory ganglia; co-expression with other neurochemical
      substances.
AB  - Immunohistochemistry for brain-derived neurotrophic factor (BDNF) was performed
      on the rat vagal and glossopharyngeal sensory ganglia. In the jugular, petrosal
      and nodose ganglia, 56.1+/-5.5%, 52.4+/-9.4% and 80.0+/-3.0% of sensory neurons,
      respectively, were immunoreactive for BDNF. These neurons were small- to medium
      sized and observed throughout the ganglia. In the solitary tract nucleus, the
      neuropil showed BDNF immunoreactivity. A double immunofluorescence method
      demonstrated that BDNF-immunoreactive neurons were also immunoreactive for
      calcitonin gene-related peptide (CGRP), P2X3 receptor, the capsaicin receptor
      (VR1) or vanilloid receptor 1-like receptor (VRL-1) in the jugular (CGRP, 43.5%;
      P2X3 receptor, 51.1%; VR1, 71.7%; VRL-1, 0.5%), petrosal (CGRP, 33.2%; P2X3
      receptor, 58.4%; VR1, 54.2%; VRL-1, 23.3%) and nodose ganglia (CGRP, 1.8%; P2X3
      receptor, 49.1%; VR1, 70.7%; VRL-1, 11.5%). The co-expression with tyrosine
      hydroxylase was also detected in the petrosal (2.9%) and nodose ganglia (2.2%).
      However, BDNF-immunoreactive neurons were devoid of parvalbumin in these ganglia.
      The present findings suggest that BDNF-containing vagal and glossopharyngeal
      sensory neurons have nociceptive and chemoreceptive functions.

PMID- 17512914
TI  - Specific regional distribution of protein arginine methyltransferase 8 (PRMT8) in
      the mouse brain.
AB  - The regional distribution of PRMT8 transcript was examined in mouse brain using
      in situ hybridization (ISH) histochemistry. The PRMT8 cRNA probe was specifically
      hybridized with CNS and the signals were observed only in the neurons. The
      distribution of the neurons expressing PRMT8 mRNA was not even throughout the
      brain. All of the regions related to general somatosensory system expressed PRMT8
      mRNA strongly. Most of the relay nuclei intervening the special somatosensory
      system, such as the auditory, visual, and vestibular systems, were packed with
      PRMT8 mRNA expressing neurons. Forebrain limbic areas and thalamic nuclei
      relevant to limbic areas were also strongly labeled with the probe. Some areas
      related to the motor system, such as the caudate putamen, Purkinje cells,
      inferior olivary nucleus and cerebellar nuclei expressed PRMT8 mRNA strongly.
      These findings suggest that PRMT8 is chiefly involved in the somatosensory and
      limbic systems, and a part of motor system.

PMID- 17512915
TI  - [3H]-L-685,458 as a radiotracer that maps gamma-secretase complex in the rat
      brain: relevance to Abeta genesis and presence of active presenilin-1 components.
AB  - Gamma-secretase is a multimeric enzyme important for normal cell/neuronal
      proliferation, differentiation and plasticity. Determining in vivo gamma
      secretase expression and activity remains a challenge because its subunit
      proteins can exist in immature and preassembled forms, but may execute cellular
      roles irrelevant to gamma-site cleavage. In this study, we characterized [3H]-L
      685,458 as a radiotracer for the detection of active gamma-secretase in adult rat
      brain. In vitro autoradiography indicated that [3H]-L-685,458 binding was
      saturatable, displaceable by peptidomimetic and small molecule gamma-secretase
      inhibitors, and exhibited rapid association and dissociation kinetics. In
      cultured hippocampal slices, [3H]-L-685,458 binding density correlated with Abeta
      reduction following in-dish dosing of this radioligand or a non-radioactive gamma
      secretase inhibitor. [3H]-L-685,458 binding sites in the adult brain were
      differentially distributed across regions and laminas, with heavy binding
      localized to the olfactory glomeruli, hippocampal CA3 and cerebellar molecular
      layer, and moderate binding in the cerebral cortex, amygdala and selected
      subcortical regions. All of these regions showed labeling for presenilin-1 N
      terminal fragments (PS1-NTFs). A distinct correlation of dense binding sites with
      abundant presence of PS1-NTFs was verified in hippocampal mossy fiber terminals
      and olfactory bulb glomeruli, suggestive of a rich expression of gamma-secretase
      in the synapses at these locations that are characteristic of dynamic plasticity.
      Together, [3H]-L-685,458 is an excellent radiotracer for mapping active gamma
      secretase complex, and may serve as a useful tool for studying the enzyme in vivo
      and in vitro.

PMID- 17512916
TI  - Effect of treadmill exercise on cell damage in rat hippocampal slices submitted
      to oxygen and glucose deprivation.
AB  - We have recently demonstrated that high intensity training exercise exacerbates
      brain damage, while a moderate intensity (2 weeks of 20 min/day of treadmill
      training) reduces the injury caused by in vitro ischemia, oxygen and glucose
      deprivation (OGD), to hippocampal slices from Wistar rats. In the present paper,
      the effect of different running programs on severity of ischemic OGD lesion was
      examined, by the evaluation of three protocols designed to simulate exercise
      conditions common to humans: one or three 20-min sessions per week, during 12
      weeks (moderate intensity), and two 20-min daily sessions for 3 weeks. OGD caused
      an increase of lactate dehydrogenase (LDH) release into the incubation media, a
      marker of tissue necrosis, and a decline of cell viability, as assessed by the
      decrease of mitochondrial dehydrogenase activity (MTT method). Moderate exercise,
      three times a week during 12-week treadmill training, decreased LDH release after
      OGD, while one weekly session and 3 weeks of two daily sessions did not affect
      OGD-induced LDH released. No exercise protocol evaluated altered MTT reduction.
      Our data support the hypothesis that moderate intensity exercise reduces
      hippocampal susceptibility to in vitro ischemia.

PMID- 17512917
TI  - Physical activity fails to rescue hippocampal neurogenesis deficits in the R6/2
      mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      linked to a mutation in the huntingtin gene leading to protein aggregation in
      neurons. The generation of new neurons in neurogenic regions, such as the
      subventricular zone of the lateral ventricle and the dentate gyrus of the
      hippocampus, is affected by these aggregation processes. In particular,
      hippocampal neurogenesis is reduced in the R6/2 transgenic mouse model of HD.
      Since physical activity stimulates adult hippocampal neurogenesis, we examined
      whether running is capable to rescue the impaired hippocampal neurogenesis in
      R6/2 mice. Proliferation of hippocampal cells measured by proliferating cell
      nuclear antigen (PCNA) marker was reduced in R6/2 animals by 64% compared to wild
      type mice. Accordingly, newly generated neurons labeled with doublecortin (DCX)
      were diminished by 60% in the hippocampus of R6/2 mice. Furthermore, the number
      of newly generated mature neurons was decreased by 76%. Within the hippocampus of
      wild type animals, a four-week running period resulted in a doubling of PCNA-,
      DCX-, and bromo-deoxyuridine (BrdU)-labeled cells. However, physical exercise
      failed to stimulate proliferation and survival of newly generated neurons in R6/2
      transgenic mouse model of HD. These findings suggest that mutant huntingtin
      alters the hippocampal microenvironment thus resulting in an impaired
      neurogenesis. Importantly, this adverse microenvironment impeded neurogenesis
      upregulation such as induced by physical exercise. Future studies need to
      decipher the molecular pathways involved in repressing the generation of new
      neurons after physical activity in huntingtin transgenic rodents.

PMID- 17512918
TI  - A CRF(2) agonist administered into the central nucleus of the amygdala decreases
      ethanol self-administration in ethanol-dependent rats.
AB  - Alcohol dependence is characterized by excessive consumption, loss of control
      over intake and the presence of a withdrawal syndrome, including both
      motivational and physical symptoms. Previous studies have implicated the brain
      corticotropin-releasing factor (CRF) stress systems in mediating the negative
      emotional state associated with ethanol withdrawal. CRF(1) receptor-specific
      antagonists, administered systemically, and CRF receptor subtype nonspecific
      antagonists, administered into the central nucleus of the amygdala (CeA),
      selectively decrease the anxiety-like behaviors and increased ethanol self
      administration associated with ethanol withdrawal. In the present study, we
      investigated the role of CRF(2) receptors within the CeA in mediating ethanol
      self-administration in ethanol-dependent and nondependent animals. Male Wistar
      rats were made dependent on ethanol using an intermittent ethanol vapor exposure
      paradigm. Nondependent animals received similar conditions but were exposed to
      air only. Following 2 h of withdrawal from ethanol vapors, ethanol and water self
      administration were measured following administration of urocortin 3, a highly
      selective CRF(2) agonist, in the CeA. In dependent rats, urocortin 3 (0.1
      microg/microl and 0.5 microg/microl) decreased ethanol self-administration, with
      no effect on water self-administration. In nondependent rats, urocortin 3 (0.5
      microg/microl) increased ethanol self-administration, with no effect on water
      self-administration. These data demonstrate an opposing role of the CRF(2)
      receptor subtype within the CeA in mediating ethanol self-administration in
      withdrawn, dependent and nondependent rats.

PMID- 17512919
TI  - Effects of concurrent visual tasks on cortico-muscular synchronization in humans.
AB  - To study the effects of external visual stimulation on motor cortex-muscle
      synchronization, coherence between electroencephalography (EEG) and
      electromyography (EMG) was measured in normal subjects under Before, Task (visual
      task: Ignore or Count, or arithmetic task) and After conditions. The control
      (Before and After) conditions required the subject to maintain first dorsal
      interosseous muscle contraction without visual stimulation. In the visual task, a
      random series of visual stimuli were displayed on a screen while the subjects
      maintained the muscle contraction. The subjects were asked to ignore the stimuli
      in the Ignore condition and to count certain stimuli in the Count condition.
      Also, in the arithmetic task, the subjects were asked to perform a simple
      subtraction. The EEG-EMG coherence found at C(3) site at 13-30 Hz (beta) was
      increased and sustained in magnitude during the Ignore and Count conditions,
      respectively. To examine the cause of the change of coherence, changes of EEG and
      EMG spectral power were computed for each frequency band. There was little change
      in the EMG spectral power in any frequency bands. While the spectral power of EEG
      unchanged in the beta band, it significantly increased and decreased in the range
      of 8-12 Hz and of 31-50 Hz, respectively, for both Ignore and Count conditions,
      not only at the C(3) site but at various sites as well. These results were in
      contrast to those obtained for the arithmetic task: the beta band EEG-EMG
      coherence was attenuated and the EEG spectral power at 4-7 Hz and at 31-50 Hz
      were significantly increased and decreased, respectively. As a conclusion, the
      present results are consistent with the idea that the enhanced 8-12 Hz/decreased
      31-50 Hz oscillations affect strength of the beta band cortico-muscular
      synchronization by suppressing the visual processing.

PMID- 17512920
TI  - Functional tissue-engineered blood vessels from bone marrow progenitor cells.
AB  - OBJECTIVE: Stem cells have significant potential for development of cell-based
      therapeutics for cardiovascular tissue regeneration. METHODS: We developed a
      novel method for isolating smooth muscle cells (SMC) from ovine bone marrow using
      a tissue-specific promoter and fluorescence-activated cell sorting. RESULTS: As
      compared to vascular SMC, bone marrow-derived smooth muscle progenitor cells (BM
      SMPC) exhibited similar morphology, showed higher proliferation potential and
      expressed several SMC markers including alpha-actin, calponin, myosin heavy
      chain, smoothelin, caldesmon and SM22. When embedded in fibrin hydrogels, BM-SMPC
      contracted the matrix and displayed receptor- and non-receptor-mediated
      contractility, indicating that BM-SMPC can generate force in response to
      vasoreactive agonists. We also prepared tissue-engineered blood vessels from BM
      SMPC and BM-derived endothelial cells and implanted them into the jugular veins
      of lambs. As early as five weeks post-implantation, grafted tissues displayed a
      confluent endothelial layer overlaying the medial layer in which BM-SMPC were
      aligned circumferentially and synthesized significant amounts of collagen. In
      contrast to previous results with vascular SMC, BM-SMPC synthesized high amounts
      of elastin that was organized in a fibrillar network very similar to that of
      native vessels. CONCLUSIONS: Our results suggest that BM-SMPC may be useful in
      studying SMC differentiation and have high potential for development of cell
      therapies for the treatment of cardiovascular disease.

PMID- 17512921
TI  - Preferential binding of human XPA to the mitomycin C-DNA interstrand crosslink
      and modulation by arsenic and cadmium.
AB  - The Xeroderma Pigmentosum A (XPA) protein is involved in the DNA damage
      recognition and repair complex formation steps of nucleotide excision repair
      (NER), and has been shown to preferentially bind to various forms of DNA damage
      including bulky lesions. DNA interstrand crosslinks are of particular interest as
      a form of DNA damage, since these lesions involve both strands of duplex DNA and
      present special challenges to the repair machinery, and mitomycin C (MMC) is one
      of several useful cancer chemotherapy drugs that induce these lesions. Purified
      XPA and the minimal DNA-binding domain of XPA are both fully capable of
      preferentially binding to MMC-DNA interstrand crosslinks in the absence of other
      proteins from the NER complex. Circular dichroism (CD) and gel shift assays were
      used to investigate XPA-DNA binding and to assess changes in secondary structure
      induced as a consequence of the interaction of XPA with model MMC-crosslinked and
      unmodified DNAs. These studies revealed that while XPA demonstrates only a modest
      increase in affinity for adducted DNA, it adopts a different conformation when
      bound to MMC-damaged DNA than when bound to undamaged DNA. This change in
      conformation may be more important in recruiting other proteins into a competent
      NER complex at damaged sites than preferential binding per se. Arsenic had little
      effect on XPA binding even at toxic concentrations, whereas cadmium reduced XPA
      binding to DNA to 10-15% that of Zn-XPA, and zinc addition could only partially
      restore activity. In addition, there was little or no change in conformation when
      Cd-XPA bound MMC-crosslinked DNA even though it demonstrated preferential
      binding, which may contribute to the mechanism by which cadmium can act as a co
      mutagen and co-carcinogen.

PMID- 17512922
TI  - Transcriptional response of genes involved in cell defense system in human cells
      stressed by H2O2 and pre-treated with (Tunisian) Rhamnus alaternus extracts:
      combination with polyphenolic compounds and classic in vitro assays.
AB  - The ability of three Rhamnus alaternus leaves extracts on antigenotoxic and gene
      expression level effects was respectively investigated in a bacterial assay
      system, i.e. the SOS chromotest with Escherichia coli PQ37 and in human K562
      lymphoblast cell line. Total oligomers flavonoids (TOF) enriched, methanol and
      ethyl acetate extracts were prepared from powdered R. alaternus leaves and
      characterized quantitatively for the presence of polyphenolic compounds. We
      explored the response to oxidative stress using the transcriptional profile of
      genes in K562 cells stressed with H2O2 after incubation with plant extracts. For
      this purpose, we used a cDNA microarrays containing 82 genes related to cell
      defense, essentially represented by antioxidant and DNA repair genes. Analysis
      revealed that SOD1, AOE 372, TXN genes involved in the antioxidant defense system
      and XPC, LIG4, POLD2, PCNA genes implied in the DNA repair system were among the
      most expressed ones in the presence of the tested extracts. These results were in
      accordance with those obtained when we tested the antigenotoxic and antioxidant
      effects of the same extracts with, respectively the SOS chromotest and the
      xanthine/xanthine oxidase enzymatic assay system. The effect of the tested
      extracts on SOS response induced by both Aflatoxin B1 (AFB1: 10 microg/assay) and
      nifuroxazide (20 microg/assay) showed that the TOF extract exhibited the highest
      antimutagenic level towards the indirect mutagen AFB1. Whereas ethyl acetate
      extract showed the highest antimutagenic effect towards the direct mutagen,
      nifuroxazide. None of the tested extracts induced mutagenic activity. However all
      the tested extracts exhibited xanthine oxidase inhibiting and superoxide anions
      scavenging effects. R. alaternus extracts contain compounds with significant
      antioxidant and antigenotoxic activities. These compounds modulate gene
      expression as detected by using cDNA arrays.

PMID- 17512923
TI  - Remnant lipoproteins stimulate proliferation and activate MAPK and Akt signaling
      pathways via G protein-coupled receptor in PC-3 prostate cancer cells.
AB  - BACKGROUND: Hypertriglyceridemia was recently shown to be a risk factor for
      prostate cancer; however, there are only a few reports about the relationship
      between prostate cancer and TG (triglycerides) rich lipoproteins. Remnant
      lipoproteins (RLP) are TG-rich lipoproteins, which are produced by the hydrolysis
      of very low density lipoproteins and chylomicrons. We examined the direct effect
      of RLP on the proliferation and signal transduction of prostate cancer cells.
      METHODS: RLP were isolated from human serum with an immunoaffinity mixed gel
      containing anti-apoA-1 and anti-apoB-100. We evaluated RLP-induced cell
      proliferation by using MTS assay. Moreover we examined the direct effect of RLP
      on the MAPK and Akt signal transductions which are reported to be correlated with
      prostate cancer by using Western blotting. RESULTS: Incubation in the presence of
      RLP for 48 h induced the proliferation of prostate cancer PC-3 cells more
      significantly than prostate cancer LNCaP cells and human prostate stromal cells.
      In PC-3 cells, RLP also induced the phosphorylation of MEK/ERK via a G protein
      coupled receptor-protein kinase C dependent pathway. Moreover, activation of Akt
      pathway was observed after RLP treatment of PC-3. CONCLUSION: These findings
      suggested that hypertriglyceridemia, especially remnant hyperlipoproteinemia,
      might be one of the progressive factors for prostate cancer.

PMID- 17512924
TI  - Molecular assay of -alpha(3.7) and -alpha(4.2) deletions causing alpha
      thalassemia by denaturing high-performance liquid chromatography.
AB  - OBJECTIVES: alpha-Thalassemia, the most common single gene disorder in humans, is
      due to the absence of one (-alpha/alphaalpha) or both (--/alphaalpha) of the two
      functional alpha-globin genes (alpha1 and alpha2). The -alpha(3.7) and 
      alpha(4.2) single gene deletions are common in Southeast Asian populations.
      Southern blotting analysis and gap PCR assay are commonly used for the detection
      of such alpha-thalassemia genotypes. The two genes are located on chromosome 16,
      with high homology (>96%). DESIGN AND METHODS: Based on the sequence variation
      within the two Z boxes, a denaturing high-performance liquid chromatography
      (DHPLC)-based assay was developed for rapid genotyping of the -alpha(3.7) and 
      alpha(4.2) alleles. To demonstrate the utility of this approach, 40 DNA samples
      with known genotypes were analyzed, including -alpha(3.7)/alphaalpha (7 cases), 
      alpha(4.2)/alphaalpha (4 cases), -alpha(3.7)/--(SEA) (6 cases), -alpha(4.2)/-
      (SEA) (3 cases), and 20 unaffected subjects (alphaalpha/alphaalpha). RESULTS: We
      successfully distinguished all of the alpha-thalassemia genotypes through their
      characteristic chromatograms of alpha1 and alpha2 genes. The accuracy of this
      technique for our sample was 100% sensitivity and specificity. CONCLUSION: This
      novel and alternative DHPLC-based alpha-thalassemia genotype assay is easy,
      rapid, and highly accurate. This technique enables the diagnosis of silent alpha+
      thalassemia and hemoglobin H disease for large scale population screening.

PMID- 17512925
TI  - Dystroglycan regulates structure, proliferation and differentiation of
      neuroepithelial cells in the developing vertebrate CNS.
AB  - In the developing CNS alpha- and beta-dystroglycan are highly concentrated in the
      endfeet of radial neuroepithelial cells at the contact site to the basal lamina.
      We show that injection of anti-dystroglycan Fab fragments, knockdown of
      dystroglycan using RNAi, and overexpression of a dominant-negative dystroglycan
      protein by microelectroporation in neuroepithelial cells of the chick retina and
      optic tectum in vivo leads to the loss of their radial morphology, to
      hyperproliferation, to an increased number of postmitotic neurons, and to an
      altered distribution of several basally concentrated proteins. Moreover, these
      treatments also altered the oriented growth of axons from retinal ganglion cells
      and from tectal projection neurons. In contrast, expression of non-cleavable
      dystroglycan protein in neuroepithelial cells reduced their proliferation and
      their differentiation to postmitotic neurons. These results demonstrate that
      dystroglycan plays a key role in maintaining neuroepithelial cell morphology, and
      that interfering with dystroglycan function influences proliferation and
      differentiation of neuroepithelial cells. These data also suggest that an
      impaired dystroglycan function in neuroepithelial cells might be responsible for
      some of the severe brain abnormalities observed in certain forms of congenital
      muscular dystrophy.

PMID- 17512926
TI  - Andrographolide induces cell cycle arrest at G2/M phase and cell death in HepG2
      cells via alteration of reactive oxygen species.
AB  - The cytotoxicity of andrographolide to HepG2 human hepatoma cells was
      investigated in the present study. Growth of HepG2 cells was affected in the
      presence of andrographolide with an IC(50) of 40.2 microM after 48 h treatment.
      Flow cytometric analysis and DNA fragmentation assay revealed that
      andrographolide induced cell cycle arrest at G2/M phase and a late apoptosis of
      the cells. The occurrence of cell cycle arrest was accompanied by the collapse of
      mitochondrial membrane potential (MMP) and an intracellular increase of hydrogen
      peroxide (H(2)O(2)) but a decrease of superoxide radicals (O(2)(-)) and reduced
      glutathione. In the treated cells, expression of Bax as well as the
      transcriptional controller of this pro-apoptotic gene, p53, was upregulated but
      not other apoptotic proteins such as Bad, Bcl-2 and Bcl-X(L). Although the
      activity of caspase-3, which has direct effect on apoptosis, was also enhanced by
      the presence of andrographolide, cell death of HepG2 could neither be prevented
      by a specific inhibitor of capsase-3 nor the pan-caspase inhibitor-zVAD (Val-Ala
      Asp), indicating that it was a caspase-independent cell death. Since the overall
      percentage of apoptotic cells was relatively small throughout the experimental
      studies, we conclude that the cytotoxic effect of andrographolide on HepG2 cells
      is primary attributed to the induction of cell cycle arrest via the alteration of
      cellular redox status.

PMID- 17512927
TI  - Curative-like analgesia in a neuropathic pain model: parametric analysis of the
      dose and the duration of treatment with a high-efficacy 5-HT(1A) receptor
      agonist.
AB  - High-efficacy activation of central 5-HT(1A) receptors by means of the recently
      discovered, selective 5-HT(1A) receptor ligand, F 13640 [(3-chloro-4-fluoro
      phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]methyl}piperidin-1
      yl]methanone, fumaric acid salt] causes an unprecedented, broad-spectrum
      analgesia in rat models of acute and chronic pain of nociceptive and neuropathic
      origin; it also is effective in conditions where opioids either are ineffective,
      induce analgesic tolerance, or elicit persistent hyperalgesia/allodynia.
      Inversely mirroring morphine's actions, F 13640's ("curative-like") analgesic
      effects persist after the discontinuation of treatment. Here, we examined the
      relationships, if any, between the dose and the duration of F 13640 treatment on
      the one hand, and the duration of persistent analgesia on the other. Rats
      received unilateral infraorbital nerve injury and developed allodynia - as
      assessed by an increased response to von Frey filament stimulation - within 24
      days; thereafter, using osmotic pumps, rats were subcutaneously infused with F
      13640 in two experiments. In one, a one-week infusion was instituted at 0.04-10
      mg/day doses; in a second experiment, a 0.63-mg/day dose was implemented for a
      duration ranging from 1 to 56 days. These 250- and 56-fold variations of the dose
      and duration of treatment caused post-treatment, persistent analgesia for about
      10 and 40 days, respectively. At least as much as dose, the duration of F 13640
      treatment determines F 13640-induced persistent analgesia. Neuroadaptive
      modulations at pre- and postsynaptic, brain and spinal cord 5-HT(1A) receptors
      may be involved in the dynamical, dose- and time-dependent, pre-treatment rise
      and post-treatment decay of the analgesia induced by high-efficacy 5-HT(1A)
      receptor activation.

PMID- 17512929
TI  - Novel functions of vimentin in cell adhesion, migration, and signaling.
AB  - Vimentin is the major intermediate filament (IF) protein of mesenchymal cells. It
      shows dynamically altered expression patterns during different developmental
      stages and high sequence homology throughout all vertebrates, suggesting that the
      protein is physiologically important. Still, until recently, the real tasks of
      vimentin have been elusive, primarily because the vimentin-deficient mice were
      originally characterized as having a very mild phenotype. Recent studies have
      revealed several key functions for vimentin that were not obvious at first sight.
      Vimentin emerges as an organizer of a number of critical proteins involved in
      attachment, migration, and cell signaling. The highly dynamic and complex
      phosphorylation of vimentin seems to be a likely regulator mechanism for these
      functions. The implicated novel vimentin functions have broad ramifications into
      many different aspects of cell physiology, cellular interactions, and organ
      homeostasis.

PMID- 17512928
TI  - The WD repeat protein FAN regulates lysosome size independent from abnormal
      downregulation/membrane recruitment of protein kinase C.
AB  - FAN (factor associated with neutral sphingomyelinase [N-SMase] activation)
      exhibits striking structural homologies to Lyst (lysosomal trafficking
      regulator), a BEACH protein whose inactivation causes formation of giant
      lysosomes/Chediak-Higashi syndrome. Here, we show that cells lacking FAN show a
      statistically significant increase in lysosome size (although less pronounced as
      Lyst), pointing to previously unrecognized functions of FAN in regulation of the
      lysosomal compartment. Since FAN regulates activation of N-SMase in complex with
      receptor for activated C-kinase (RACK)1, a scaffolding protein that recruits and
      stabilizes activated protein kinase C (PKC) isotypes at cellular membranes, and
      since an abnormal (calpain-mediated) downregulation/membrane recruitment of PKC
      has been linked to the defects observed in Lyst-deficient cells, we assessed
      whether PKC is also of relevance in FAN signaling. Our results demonstrate that
      activation of PKC is not required for regulation of N-SMase by FAN/RACK1.
      Conversely, activation of PKC and recruitment/stabilization by RACK1 occurs
      uniformly in the presence or absence of FAN (and equally, Lyst). Furthermore,
      regulation of lysosome size by FAN is not coupled to an abnormal
      downregulation/membrane recruitment of PKC by calpain. Identical results were
      obtained for Lyst, questioning the previously reported relevance of PKC for
      formation of giant lysosomes and in Chediak-Higashi syndrome. In summary, FAN
      mediates activation of N-SMase as well as regulation of lysosome size by
      signaling pathways that operate independent from activation/membrane recruitment
      of PKC.

PMID- 17512930
TI  - Cellular responses to disruption of the permeability barrier in a three
      dimensional organotypic epidermal model.
AB  - Repeated injury to the stratum corneum of mammalian skin (caused by friction,
      soaps, or organic solvents) elicits hyperkeratosis and epidermal thickening.
      Functionally, these changes serve to restore the cutaneous barrier and protect
      the organism. To better understand the molecular and cellular basis of this
      response, we have engineered an in vitro model of acetone-induced injury using
      organotypic epidermal cultures. Rat epidermal keratinocytes (REKs), grown on a
      collagen raft in the absence of any feeder fibroblasts, developed all the
      hallmarks of a true epidermis including a well-formed cornified layer. To induce
      barrier injury, REK cultures were treated with intermittent 30-s exposures to
      acetone then were fixed and paraffin-sectioned. After two exposures, increased
      proliferation (Ki67 and BrdU staining) was observed in basal and suprabasal
      layers. After three exposures, proliferation became confined to localized buds in
      the basal layer and increased terminal differentiation was observed (compact
      hyperkeratosis of the stratum corneum, elevated levels of K10 and filaggrin, and
      heightened transglutaminase activity). Thus, barrier disruption causes epidermal
      hyperplasia and/or enhances differentiation, depending upon the extent and
      duration of injury. Given that no fibroblasts are present in the model, the
      ability to mount a hyperplastic response to barrier injury is an inherent
      property of keratinocytes.

PMID- 17512931
TI  - Involvement of RNA binding proteins AUF1 in mammary gland differentiation.
AB  - The expression of many genes, such as beta-casein, c-myc, and cyclin D1, is
      altered by lactogenic hormone stimulation during mammary epithelial cell
      differentiation. Here, we demonstrate that post-transcriptional regulation plays
      an important role to establish gene expression required to initiate milk
      production as well as transcriptional control. AUF1 protein, a member of the AU
      rich element (ARE)-binding protein family, plays a role in ARE-mRNA turnover by
      regulating mRNA stability and/or translational control. Cytoplasmic localization
      of AUF1 protein is critically linked to function. We show that as the mammary
      gland differentiates, AUF1 protein moves from the cytoplasm to the nucleus.
      Moreover, in mammary gland epithelial cells (HC11), stimulation by lactogenic
      hormone decreased cytoplasmic and increased nuclear AUF1 levels. Direct binding
      of AUF1 protein was observed on c-myc mRNA, but not beta-casein or cyclin D1
      mRNA. AUF1 downregulation in HC11 cells increased the expression of beta-casein
      mRNA and decreased the expression of c-myc mRNA by lactogenic hormone.
      Conversely, overexpression of AUF1 inhibited these effects of lactogenic hormone
      stimulation in HC11 cells. These results suggest that AUF1 participates in
      mammary gland differentiation processes under the control of lactogenic hormone
      signals.

PMID- 17512932
TI  - Reversal of ERK activation in the dorsal horn after decompression in chronic
      constriction injury.
AB  - Injury-induced neuropathic pain is related to changes in the central terminals of
      dorsal root ganglia neurons, i.e., dorsal horn plasticity. We investigated the
      influences of decompression by removing ligatures producing chronic constriction
      injury (CCI) in Sprague-Dawley rats at postoperative week (POW) 4, the
      decompression group; for comparison, all ligatures remained through the
      experimental period in the CCI group. The effect was evaluated with extracellular
      signal-regulated kinase (ERK) activation in the dorsal horn, i.e., number of
      phosphorylated ERK (+) cells in the dorsal horn. At POW 1, the dorsal horn
      indexes had increased to a similar degree in both groups (2.40+/-0.58 vs. 2.27+/
      0.36, p=0.73). At POW 8, thermal hyperalgesia and mechanical allodynia had
      completely disappeared with a normalization of dorsal horn index (1.17+/-0.11 vs.
      1.02+/-0.12 at POW 0, p=0.07) in the decompression group; in contrast, the dorsal
      horn index remained elevated in the CCI group (2.48+/-0.30, p<0.001) with
      persistent neuropathic pain behaviors at POW 8. This report suggests that ERK
      activation in the dorsal horn is correlated with neuropathic pain behaviors and
      its normalization reflects the reversal of neuropathic pain behaviors after
      decompression.

PMID- 17512933
TI  - A ratio control scheme decoupling disturbance response from set-point response.
AB  - In this paper a novel ratio control scheme is proposed for stable and unstable
      processes with time delay. The proposed ratio control system consists of two
      control loops with two-degrees-of-freedom control structure, which decouples the
      set-point response of each loop from its disturbance response. Two ratio
      controllers separately for the set-point and load disturbance changes are
      introduced between the two control loops, in order to achieve improved ratio
      control performance during the transients caused by the set-point and disturbance
      changes and to decouple the set-point response of the whole ratio control system
      from its disturbance response. For easy understanding and tuning, all the
      controllers in the ratio control system are designed analytically. As a result,
      the set-point and load disturbance responses of the ratio control system can be
      independently and conveniently tuned by a single control parameter. In addition,
      the proposed ratio control scheme can provide quantitative performance
      estimation. Simulation examples are included to illustrate the effectiveness of
      the proposed method.

PMID- 17512934
TI  - Cooperative-feedback control.
AB  - In this work a control structure capable of handling controllability problems,
      which emerge from the presence of constraints, and improve the performance of the
      system by coordinating the use of several manipulated variables is introduced. In
      this scheme, the primary manipulated variable is used to handle the transient
      response while the auxiliary manipulated variable is used to keep the primary
      manipulated variable away from saturation. These two manipulated variables are
      coordinated through a user-defined non-linear function, which decides when and
      how the control structure changes. Its parameters determine the interaction
      between both inputs and the steady state value of each manipulated variable. The
      effectiveness of the proposed scheme is illustrated in two simulation examples.

PMID- 17512935
TI  - Pregnancy-induced hypertension and infant mortality in triplets.
AB  - OBJECTIVE: To assess the effects of pregnancy-induced hypertension on infant
      mortality in triplets stratified by gestational age at birth. METHODS: A
      retrospective cohort study was conducted using the linked 1995-2000 US
      birth/infant death database. Generalized estimating equations were used to
      evaluate the observed association. RESULTS: Pregnancy-induced hypertension was
      associated with lesser neonatal mortality (odds ration [OR]: 0.34, 95% CI: 0.21,
      0.54), postneonatal mortality (OR: 0.54, 95% CI: 0.30, 0.99) and infant mortality
      (OR, 0.37, 95% CI: 0.25, 0.55) in triplets. It was also associated with a
      decreased risk of neonatal death (OR, 0.38; 95% CI, 0.21-0.67), postneonatal
      death (OR, 0.45; 95% CI, 0.21-0.97), and infant death (OR, 0.39; 95% CI, 0.24
      0.64) in early preterm triplets, whereas the association was not significant in
      late preterm or in full-term triplets. CONCLUSION: Pregnancy-induced hypertension
      is associated with a decreased risk of infant mortality in triplets. This effect
      varies with gestational age at birth.

PMID- 17512936
TI  - Determination of chlorophenols in water samples using simultaneous dispersive
      liquid-liquid microextraction and derivatization followed by gas chromatography
      electron-capture detection.
AB  - Simultaneous dispersive liquid-liquid microextraction (DLLME) and derivatization
      combined with gas chromatography-electron-capture detection (GC-ECD) was used to
      determine chlorophenols (CPs) in water sample. In this derivatization/extraction
      method, 500 microL acetone (disperser solvent) containing 10.0 microL
      chlorobenzene (extraction solvent) and 50 microL acetic anhydride (derivatization
      reagent) was rapidly injected by syringe in 5.00 mL aqueous sample containing CPs
      (analytes) and K(2)CO(3) (0.5%, w/v). Within a few seconds the analytes
      derivatized and extracted at the same time. After centrifugation, 0.50 microL of
      sedimented phase containing enriched analytes was determined by GC-ECD. Some
      effective parameters on derivatization and extraction, such as extraction and
      disperser solvent type and their volume, amount of derivatization reagent,
      derivatization and extraction time, salt addition and amount of K(2)CO(3) were
      studied and optimized. Under the optimum conditions, enrichment factors and
      recoveries are in the range of 287-906 and 28.7-90.6%, respectively. The
      calibration graphs are linear in the range of 0.02-400 microg L(-1) and limit of
      detections (LODs) are in the range of 0.010-2.0 microg L(-1). The relative
      standard deviations (RSDs, for 200 microg L(-1) of MCPs, 100 microg L(-1) of
      DCPs, 4.00 microg L(-1) of TCPs, 2.00 microg L(-1) of TeCPs and PCP in water)
      with and without using internal standard are in the range of 0.6-4.7% (n=7) and
      1.7-7.1% (n=7), respectively. The relative recoveries of well, tap and river
      water samples which have been spiked with different levels of CPs are 91.6-104.7,
      80.8-117.9 and 83.3-101.3%, respectively. The obtained results show that
      simultaneous DLLME and derivatization combined with GC-ECD is a fast simple
      method for the determination of CPs in water samples.

PMID- 17512937
TI  - Development and validation of a stability-indicating reversed-phase high
      performance liquid chromatography method for assay of betamethylepoxide and
      estimation of its related compounds.
AB  - Betamethylepoxide (16beta-methyl-Delta(1,4)-pregnadiene-9beta-11beta-oxide
      17alpha,21-diol-3,20-dione) is a key intermediate for the synthesis of various
      active pharmaceutical ingredients (APIs) of steroid compounds. A stability
      indicating reversed-phase HPLC method for assay of betamethylepoxide and
      estimation of its related compounds has been developed and validated. This method
      can accurately quantitate betamethylepoxide in the presence of numerous
      structurally related compounds (including the alpha-epimer, known as
      alphamethylepoxide). This method can also adequately separate most of the
      impurities from each other and estimate their quantities in betamethylepoxide
      samples. The stability-indicating capability of this method has been demonstrated
      by adequate separation of the degradation products from betamethylepoxide in
      stress degraded and aged stability samples. The HPLC column used in the method
      was a 5 cm YMC Hydrosphere C(18) column (4.6 mm I.D.) and the mobile phase
      consisted of (A) water and (B) acetonitrile:methanol (8:25, v/v).

PMID- 17512938
TI  - Recent studies of the electrospray ionisation behaviour of selected drugs and
      their application in capillary electrophoresis-mass spectrometry and liquid
      chromatography-mass spectrometry.
AB  - This review is concerned with recent studies of electrospray ionisation-mass
      spectrometry (ESI-MS) of selected small molecular mass drugs and their
      application in qualitative and quantitative analytical methods using the
      techniques liquid chromatography mass spectrometry (LC-ESI-MS) and capillary
      electrophoresis mass spectrometry (CE-ESI-MS). The publications reviewed are
      taken from the Web of Knowledge database for the year 2006. The drugs have
      molecular mass less than 1000 Da and are chosen according to selected drug
      classifications in which they give ESI signals primarily as [M+H]+ ions. The drug
      classifications are antibiotics/antibacterials, steroids, anti-tumour drugs,
      erectile dysfunction agents, anti-epileptic drugs, antiasthmatic drugs,
      psychoactive drugs and miscellaneous drugs. Details are given on the
      fragmentations, where available, that these ionic species exhibit in-source and
      in ion trap, triple quadrupole and time-of-flight mass spectrometers. Analytical
      methods for the detection and determination of these small molecular mass drug
      molecules are also discussed, where appropriate, under the particular drug
      classifications. Analytical information on, for example, sample concentration
      techniques, separation conditions, recoveries from biological media and limits of
      detection/quantitation (LODs and LOQs) are provided.

PMID- 17512939
TI  - Comparison of reversed-phase liquid chromatography-mass spectrometry with
      electrospray and atmospheric pressure chemical ionization for analysis of dietary
      tocopherols.
AB  - ESI and APCI ionization techniques in both negative and positive ion modes were
      evaluated for simultaneous LC-MS analysis of the four tocopherol homologues
      (alpha, beta, gamma and delta). The ESI and APCI ionization of tocopherols in
      positive ion mode was not efficient and proceeded via two competitive mechanisms,
      with the formation of protonated pseudo-molecular ions and molecular ions, which
      adversely influenced the repeatability of MS signal. Ionization in negative ion
      mode in both ESI and APCI was more efficient as it only produced target
      deprotonated pseudo-molecular ions. The APCI in negative ion mode showed larger
      linearity range, lower detection limits and was less sensitive to the differences
      in chemical structure of analytes and nature of applied solvents than negative
      ion ESI. Negative ion APCI was, therefore, chosen for the development of LC-MS
      method for simultaneous determination of the four tocopherols in foods. A
      baseline separation of the tocopherols was achieved on novel pentafluorophenyl
      silica-based column Fluophase PFP. The use of methanol-water (95:5, v/v) as a
      mobile phase was preferable to the use of acetonitrile-water due to considerable
      gain in MS signal. The limits of quantifications were 9 ng/mL for alpha
      tocopherol, 8 ng/mL for beta- and gamma- and 7.5 ng/mL for delta-tocopherol when
      2 microL was injected. This method was successfully applied to determination of
      tocopherols in sunflower oil and milk.

PMID- 17512940
TI  - Qualitative analysis of phenols and alcohols in complex samples after
      derivatization to esters of ferrocene carboxylic acid by gas chromatography with
      mass spectrometric detection.
AB  - Phenols and alcohols in complex petrochemical samples are derivatized to esters
      of ferrocene carboxylic acid in a rapid and simple reaction. These esters show
      several characteristic ions of high intensity in gas chromatography coupled with
      electron impact ionization mass spectrometry (GC-EI-MS) which can be used for the
      identification of the analyte. A differentiation between alcohols and phenols is
      possible due to the McLafferty rearrangement shown only by the alcohol esters.
      Selective ion monitoring of m/z 213 yields a phenol-selective chromatogram and
      m/z 230 an alcohol-selective chromatogram. For all iron containing fragments, the
      isotopic pattern of iron can be observed which enhances the reliability of the
      peak identification. The ferrocene esters of 11 alcohols, 20 alkylphenols
      (including octyl- and nonylphenol), phenylphenol, naphthol and
      hydroxyphenanthrene, several chloro- and all mononitrophenols were synthesized as
      well as the esters of pentadeutero- and two fluorinated phenols. Their
      fragmentation pattern under EI ionization is studied and a GC-ion trap-MS system
      was optimized for simultaneous use of the full scan mode and an MS/MS experiment
      in the same run. This provides for a very high selectivity in the detection of
      the esters and makes available the complete mass spectra without any additional
      measurements. The benefits of the simple and rapid derivatization procedure in
      combination with this powerful detection method are demonstrated for selected
      petrochemical samples. Several alkylphenols could be successfully identified in
      such samples and molecular information about unknown phenolic components could be
      easily obtained.

PMID- 17512941
TI  - Composite structure of temperature sensitive chitosan microgel and anomalous
      behavior in alcohol solutions.
AB  - Poly(N-isopropylacrylamide)/chitosan (PNIPAM/CS) core-shell microgel was
      synthesized by graft copolymerization. The microstructure of copolymers was
      characterized by FT-IR spectrum and (1)H-nuclear magnetic resonance ((1)H NMR).
      Transmission electron microscope (TEM) and dynamic light scattering (DLS)
      measurements display that the microgel has high monodispersity and with a core
      shell structure. For swelling the microgel in various alcohol solutions, the
      particles first shrink; then flocculation occurs resulted from weak aggregation
      of particles with the increase of alcohol concentration. The investigation of the
      size of microgels as a function of temperature shows that the thermo-sensitive
      property is markedly exhibited when the alcohol concentration is low, and
      vanishes when the alcohol concentration exceeds some value where the microgels
      have the lowest size.

PMID- 17512942
TI  - Children's metacognitive judgments in an eyewitness identification task.
AB  - Two experiments examined children's metacognitive monitoring of recognition
      judgments within an eyewitness identification paradigm. A confidence-accuracy
      (CA) calibration approach was used to examine patterns of calibration, over
      /underconfidence, and resolution. In Experiment 1, children (n=619, mean age=11
      years 10 months) and adults (n=600) viewed a simulated crime and attempted two
      separate identifications from 8-person target-present or target-absent lineups
      given lineup instructions that manipulated witnesses choosing patterns by varying
      the degree of social pressure. For choosers, but not nonchoosers, meaningful CA
      relations were observed for adults but not for children. Experiment 2 tested a
      guided hypothesis disconfirmation manipulation designed to improve the realism of
      children's metacognitive judgments. Children (N=796, mean age=11 years 11 months)
      in experimental and control conditions viewed a crime and attempted two separate
      identifications. The manipulation had minimal impact on the CA relation for
      choosers and nonchoosers. In contrast to adults, children's identification
      confidence provides no useful guide for investigators about the likely guilt or
      innocence of a suspect. These experiments revealed limitations in children's
      metacognitive monitoring processes that have not been apparent in previous
      research on recall and recognition with younger children.

PMID- 17512943
TI  - Adult cardiac fibroblasts null for sphingosine kinase-1 exhibit growth
      dysregulation and an enhanced proinflammatory response.
AB  - Cardiac fibroblasts are critical for the maintenance of extracellular matrix
      deposition and turnover in the normal heart and are key mediators of inflammatory
      and fibrotic myocardial remodeling in the injured and failing heart. Sphingosine
      kinase (SphK) activation is a well-recognized determinant of cell fate in cardiac
      myocytes and other cells, but SphK responses have not previously been studied in
      cardiac fibroblasts. Initially we found that total SphK activity is over 10-fold
      higher in cardiac fibroblasts than in adult mouse cardiac myocytes. SphK is
      composed of two major isoforms, SphK-1 and SphK-2. In fibroblasts isolated from
      SphK-1 knockout mice, SphK activity was greatly reduced indicating that SphK-1 is
      the major isoform expressed in these cells. To determine whether SphK regulates
      cell proliferation and the proinflammatory protein inducible nitric oxide
      synthase (iNOS), we exposed cultured cardiac fibroblasts to the cytokine
      interleukin-1beta (IL-1beta) and/or hypoxia. Both hypoxia and IL-1beta alone and
      in combination enhanced fibroblast SphK activity. In wild-type fibroblasts,
      hypoxia induced proliferation, but in SphK-1 null fibroblasts this response was
      blunted even in the presence of serum. In contrast, we found that iNOS expression
      and NO production were enhanced in SphK-1 null fibroblasts during hypoxia. In
      wild-type fibroblasts, IL-1beta was only a weak inducer of iNOS and of NO
      accumulation and hypoxia alone had no significant effect on iNOS activation.
      However, IL-1beta in combination with hypoxia extensively stimulated iNOS and NO
      production, and this stimulation was enhanced in SphK-1 null fibroblasts. We
      conclude that activation of endogenous SphK-1 serves a dual regulatory function:
      it is required for optimal cardiac fibroblast proliferation but is a negative
      modulator of proinflammatory responses during hypoxia.

PMID- 17512944
TI  - A mitotic kinase TOPK enhances Cdk1/cyclin B1-dependent phosphorylation of PRC1
      and promotes cytokinesis.
AB  - A MAPKK-like mitotic kinase, TOPK, implies the formation of mitotic spindles and
      spindle midzone and accomplishing cytokinesis, however, its underlying mechanism
      remains unclear. A microtubule bundling protein, PRC1, plays a pivotal role in
      the formation of mitotic spindles and spindle midzone. Because of their
      functional resemblance, we attempted to clarify the links between these two
      molecules. TOPK supported mitotic advance via the cdk1/cyclin B1-dependent
      phosphorylation of PRC1. TOPK induced the phosphorylation of PRC1 at T481 in
      vivo, however, TOPK did not phosphorylate PRC1 in vitro. TOPK induced the
      phosphorylation of PRC1 at T481 only when the cdk1/cyclin B1 existed
      simultaneously in vitro. Both the enzymatic activity of TOPK and association
      competence of TOPK with PRC1 were mandatory for this phosphorylation. TOPK binds
      to cdk1/cyclin B1, microtubules and PRC1 via its unique region near the C
      terminus. TOPK co-localized closely with cdk1 throughout the cell cycle in vivo.
      Collectively, these data indicate that TOPK, which makes a kinase-substrate
      complex with cdk1/cyclin B1 and PRC1 on microtubules during mitosis, enhances the
      cdk1/cyclin B1-dependent phosphorylation of PRC1 and thereby strongly promotes
      cytokinesis.

PMID- 17512945
TI  - Specific recognition of a DNA immunogen by its elicited antibody.
AB  - DNA recognition by antibodies is a key feature of autoimmune diseases, yet model
      systems with structural information are very limited. The monoclonal antibody ED
      10 recognizes one of the strands of the DNA duplex used in the immunogenic
      complex. Modifications of the 5' end decrease the binding affinity and short
      oligonucleotides retain high binding affinity. We determined crystal structures
      for the Fab bound to a 6-mer oligonucleotide containing the specific sequence
      that raised the antibody and compared it with the unliganded Fab. Only the first
      two bases from the 5' end (dTdC) display electron density and we observe four key
      hydrogen bonds at the interface. The thymine ring is stacked between TrpH50 and
      TrpH95, and the cytosine ring is packed against TyrL32. Upon DNA binding, TyrH97
      and TrpH95 rearrange to allow subnanomolar binding affinity, five orders of
      magnitude higher than other reported complexes, possibly because of having gone
      through affinity maturation. This structure represents the first bona fide
      antibody DNA immunogen complex described in atomic detail.

PMID- 17512946
TI  - Chicken breast muscle connectin: passive tension and I-band region primary
      structure.
AB  - We performed cDNA cloning of chicken breast muscle connectin. Together with
      previous results, our analysis elucidated a 24.2 kb sequence encoding the amino
      terminus of the protein. This corresponded to the I-band region of the skeletal
      muscle sarcomere, which is involved in extension and contraction between the Z
      line and the A-I junction. There were fewer middle immunoglobulin domains and
      amino acid residues in the PEVK segment of chicken breast muscle connectin than
      in human skeletal muscle connectin, but more than in human cardiac muscle
      connectin. We measured passive tension generation by stretching mechanically
      skinned myofibril bundles. This revealed that appreciable tension development in
      chicken breast muscle began at longer sarcomere spacings than in rabbit cardiac
      muscle, but at shorter spacings than in rabbit psoas and soleus muscles. We
      suggest that the chicken breast muscle sarcomere remains in a relatively extended
      state even in unstrained sarcomeres. This would explain why chicken breast muscle
      does not extend under force to the same degree as rabbit psoas and soleus
      muscles.

PMID- 17512947
TI  - Intestinal LI-cadherin acts as a Ca2+-dependent adhesion switch.
AB  - Cadherins are Ca(2+)-dependent transmembrane glycoproteins that mediate cell-cell
      adhesion and are important for the structural integrity of epithelia. LI-cadherin
      and the classical E-cadherin are the predominant two cadherins in the intestinal
      epithelium. LI-cadherin consists of seven extracellular cadherin repeats and a
      short cytoplasmic part that does not interact with catenins. In contrast, E
      cadherin is composed of five cadherin repeats and a large cytoplasmic domain that
      is linked via catenins to the actin cytoskeleton. Whereas E-cadherin is
      concentrated in adherens junctions, LI-cadherin is evenly distributed along the
      lateral contact area of intestinal epithelial cells. To investigate if the
      particular structural properties of LI-cadherin result in a divergent homotypic
      adhesion mechanism, we analyzed the binding parameters of LI-cadherin on the
      single molecule and the cellular level using atomic force microscopy, affinity
      chromatography and laser tweezer experiments. Homotypic trans-interaction of LI
      cadherin exhibits low affinity binding with a short lifetime of only 1.4 s.
      Interestingly, LI-cadherin binding responds to small changes in extracellular
      Ca(2+) below the physiological plasma concentration with a high degree of
      cooperativity. Thus, LI-cadherin might serve as a Ca(2+)-regulated switch for the
      adhesive system on basolateral membranes of the intestinal epithelium.

PMID- 17512948
TI  - Effects of lithium and valproate on serum and hippocampal neurotrophin-3 levels
      in an animal model of mania.
AB  - It has been demonstrated that lithium (Li) and valproate (VPT), first line mood
      stabilizers, increase BDNF content in rat hippocampus and frontal cortex, which
      suggests that the regulation of neurotrophic factors might be associated with
      their pharmacological effects. In sight of the scarcity of studies with other
      neurotrophins, and the possible relevance of multiple neurotrophic signaling
      systems in bipolar disorder we investigated the effects of Li and VPT on NT-3
      levels in rat serum and hippocampus, using an animal model of mania induced by
      amphetamine (AMPH). In the reversal model, adult male Wistar rats received AMPH
      or saline for 14 days, and between the 8th and 14th days, animals were treated
      with Li, VPT or saline. In the prevention model, rats were pretreated with Li,
      VPT or saline, and between the 8th and 14th days, the animals received AMPH or
      saline. Li increased serum and hippocampal NT-3 levels in all conditions, whereas
      VPT increased hippocampal NT-3 in the prevention model only. Li reversed AMPH
      changes in NT-3 in the reversal model, and VPT prevented AMPH changes in NT-3 in
      the prevention model. These results suggest that both Li and VPT modulate serum
      and central (hippocampal) NT-3 levels, and further support that the regulation of
      neurotrophic signaling systems may be related to the mechanisms of action of mood
      stabilizers.

PMID- 17512949
TI  - In silico functional and structural characterisation of ferlin proteins by
      mapping disease-causing mutations and evolutionary information onto three
      dimensional models of their C2 domains.
AB  - Ferlins are C2 domain proteins involved in membrane fusion events, including
      membrane repair and synaptic exocytosis, and their deficiency can result in
      muscular dystrophy and deafness. We have undertaken a structural study of their
      C2 domains by sequence comparison and homology modelling to understand the
      function of these poorly characterised proteins and to predict the molecular
      impact of disease-causing mutations. We observe that non-conservative mutations
      affecting buried residues tend to result in detrimental phenotypes, likely
      because of decreased protein stability, whereas most variants with replacements
      in surface residues do not. The few cases of exposed residues altered in variants
      known to cause diseases are found in conserved areas of functional importance,
      including essential calcium-binding regions, as deduced by analogy to other
      characterised C2 domains. Furthermore, we report distinct features of some C2
      domains in the two known ferlin subfamilies that correlates with the presence or
      absence of the DysF domains. Taken altogether, our results highlight potential
      targets for further experimental analyses to understand the function of ferlin
      proteins. We believe our modelling data will aid the diagnosis of diseases
      associated with ferlin mutations and the development of therapeutic strategies.

PMID- 17512950
TI  - Frontal-lobe syndrome and psychosis after damage to the brainstem dopaminergic
      nuclei.
AB  - A patient developed frontal-lobe syndrome and psychotic symptoms after infarction
      in the pontomesencephalic junction. Stereotaxic lesion localization on magnetic
      resonance imaging and statistical analyses of regional cerebral blood flow (rCBF)
      disclosed an involvement of the rostral brainstem dopaminergic nuclei and
      hypoperfusion in the frontal-subcortical circuit components. We suggest that the
      patient's cognitive and behavioral disturbances were associated with disruption
      of ascending dopaminergic projections to the frontal-subcortical circuits.

PMID- 17512951
TI  - Determinants of plasma levels of brain natriuretic peptide after acute ischemic
      stroke or TIA.
AB  - Plasma levels of brain natriuretic peptide (BNP) are frequently elevated after an
      acute stroke and have been shown to be an independent predictor of mortality.
      However, the relationships between stroke and BNP concentrations have not yet
      been systematically investigated. Plasma BNP assay and echocardiography were
      performed in 48 patients with ischemic stroke or TIA with a mean delay of 12.7 h
      after onset. Median BNP concentration was 88.6 pg/mL (range 5-1270). Older age,
      chronic heart failure, atrial fibrillation, stroke severity, lower hemoglobin
      levels, lower left ventricular ejection fraction, and abnormalities of left
      atrium or appendage (LA/LAA) were univariately associated with increased BNP
      levels. At multivariable analysis, the presence of at least one LA/LAA
      abnormality (atrial dilatation, low flow velocity, spontaneous echocontrast or
      thrombus) had the strongest association with BNP, explaining 38.9% of the
      variance in the whole sample and 28.5% in patients without atrial fibrillation.
      In acute ischemic stroke patients, elevated plasma BNP levels have multiple
      determinants, among which left atrial disease appears to be the stronger, even in
      patients without atrial fibrillation. These results encourage further
      investigation of plasma BNP concentration as a potential marker of the presence
      of left atrial sources of emboli.

PMID- 17512952
TI  - Evolution of cooperation in spatial public goods games with common resource
      dynamics.
AB  - Investment in a common resource shared by all players is difficult to evolve
      despite higher returns because a non-investor (free-rider) always receives more
      than an investor (altruist). This situation is referred to as the Tragedy of the
      Commons and is often observed in various biological systems including
      environmental problems of human society. Punishment and reputation are effective
      mechanisms but require cooperator's ability to identify free-riders. Volunteering
      can work in anonymous public goods games but this requires voluntary
      participation, which is not always the case. Here, we show that the evolution of
      altruism is possible in anonymous and obligate public goods games if we consider
      the spatiotemporal dynamics of the common resource that incorporate spatial
      diffusion and internal dynamics of the commons. The investors' strategy to
      counter free-riders is to increase population density and to outnumber them with
      the common resource level kept as low as that of the free-riders.

PMID- 17512953
TI  - Binding activities by propiverine and its N-oxide metabolites of L-type calcium
      channel antagonist receptors in the rat bladder and brain.
AB  - The present study was undertaken to characterize the binding activities of
      propiverine and its N-oxide metabolites (1-methyl-4-piperidyl
      diphenylpropoxyacetate N-oxide: P-4(N-->O), 1-methyl-4-piperidyl benzilate N
      oxide: DPr-P-4(N-->O)) toward L-type calcium channel antagonist receptors in the
      rat bladder and brain. Propiverine and P-4(N-->O) inhibited specific (+)-[(3)H]PN
      200-110 binding in the rat bladder in a concentration-dependent manner. Compared
      with that for propiverine, the K(i) value for P-4(N-->O) in the bladder was
      significantly greater. Scatchard analysis has revealed that propiverine increased
      significantly K(d) values for bladder (+)-[(3)H]PN 200-110 binding. DPr-P-4(N-
      >O) had little inhibitory effects on the bladder (+)-[(3)H]PN 200-110 binding.
      Oxybutynin and N-desethyl-oxybutynin (DEOB) also inhibited specific (+)-[(3)H]PN
      200-110 binding in the rat bladder. Propiverine, oxybutynin and their metabolites
      inhibited specific [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS) binding
      in the rat bladder. The ratios of K(i) values for (+)-[(3)H]PN 200-110 to
      [(3)H]NMS were markedly smaller for propiverine and P-4(N-->O) than oxybutynin
      and DEOB. Propiverine and P-4(N-->O) inhibited specific binding of (+)-[(3)H]PN
      200-110, [(3)H]diltiazem and [(3)H]verapamil in the rat cerebral cortex in a
      concentration-dependent manner. The K(i) values of propiverine and P-4(N-->O) for
      [(3)H]diltiazem were significantly smaller than those for (+)-[(3)H]PN 200-110
      and [(3)H]verapamil. Further, their K(i) values for [(3)H]verapamil were
      significantly smaller than those for (+)-[(3)H]PN 200-110. The K(i) values of
      propiverine for each radioligand in the cerebral cortex were significantly
      (P<0.05) smaller than those of P-4(N-->O). In conclusion, the present study has
      shown that propiverine and P-4(N-->O) exert a significant binding activity of L
      type calcium channel antagonist receptors in the bladder and these effects may be
      pharmacologically relevant in the treatment of overactive bladder after oral
      administration of propiverine.

PMID- 17512955
TI  - Concentration of polybrominated diphenyl ethers (PBDEs) in sediment cores of
      Sundarban mangrove wetland, northeastern part of Bay of Bengal (India).
AB  - The paper presents the first comprehensive survey of congener profiles (12
      congeners) of polybrominated diphenyl ethers (PBDEs) in core sediment samples
      (<63 microm) covering seven sites in Sundarban mangrove wetland (India). Gas
      chromatographic analyses were carried out in GC-Ms/Ms for tri- to hepta-
      brominated congeners. Results pointed out a non-homogenous contamination of the
      wetland with summation operator(12) PBDE values ranging from 0.08 to 29.03 ngg(
      1), reflecting moderate to low contamination closely in conformity to other Asian
      aquatic environments. The general order of decreasing congener contribution to
      the total load was: BDE 47>99>100>154, similar to the distribution pattern
      worldwide. Although tetrabromodiphenyl ether BDE 47 was found in all samples
      followed by hexabromodiphenyl ether BDE-154, they were not necessarily the
      dominant congeners. No uniform temporal trend on PBDE levels was recorded
      probably due to particular hydrological characteristics of the wetland and/on non
      homologous inputs from point sources (untreated municipal wastewater and local
      industries, electronic wastes from the dump sites, etc.) of these compounds.
      Because of the propensity of PBDEs to accumulate in various compartments of
      wildlife and human food webs, evaluation of biological tissues should be
      undertaken as a high priority.

PMID- 17512956
TI  - Environmental process descriptors for TNT, TNT-related compounds and picric acid
      in marine sediment slurries.
AB  - Process descriptors were determined for picric acid, TNT, and the TNT-related
      compounds 2,4DNT, 2,6DNT, 2ADNT, 4ADNT, 2,4DANT, 2,6DANT, TNB and DNB in marine
      sediment slurries. Three marine sediments of various physical characteristics
      (particle size ranging from 15 to >90% fines and total organic carbon ranging
      from <0.10 to 3.60%) were kept in suspension with 20ppt saline water.
      Concentrations of TNT and its related compounds decreased immediately upon
      contact with the marine sediment slurries, with aqueous concentrations slowly
      declining throughout the remaining test period. Sediment-water partition
      coefficients could not be determined for these compounds since solution phase
      concentrations were unstable. Kinetic rates and half-lives were influenced by the
      sediment properties, with the finer grained, higher organic carbon sediment being
      the most reactive. Aqueous concentrations of picric acid were very stable,
      demonstrating little partitioning to the sediments. Degradation to picramic acid
      was minimal, exhibiting concentrations at or just above the detection limit.

PMID- 17512954
TI  - The cholinergic system is involved in regulation of the development of the
      hematopoietic system.
AB  - Gene expression profiling demonstrated that components of the cholinergic system,
      including choline acetyltransferase, acetylcholinesterase and nicotinic
      acetylcholine receptors (nAChRs), are expressed in embryonic stem cells and
      differentiating embryoid bodies (EBs). Triggering of nAChRs expressed in EBs by
      nicotine resulted in activation of MAPK and shifts of spontaneous differentiation
      toward hemangioblast. In vivo, non-neural nAChRs are detected early during
      development in fetal sites of hematopoiesis. Similarly, in vivo exposure of the
      developing embryo to nicotine resulted in higher numbers of hematopoietic
      progenitors in fetal liver. However postpartum, the number of hematopoietic
      stem/progenitor cells (HSPC) was decreased, suggesting an impaired colonization
      of the fetal bone marrow with HSPCs. This correlated with increased number of
      circulating HSPC and decreased expression of CXCR4 that mediates migration of
      circulating cells into the bone marrow regulatory niche. In addition, protein
      microarrays demonstrated that nicotine changed the profile of cytokines produced
      in the niche. While the levels of IL1alpha, IL1beta, IL2, IL9 and IL10 were not
      changed, the production of hematopoiesis-supportive cytokines including G-CSF, GM
      CSF, IL3, IL6 and IGFBP-3 was decreased. This correlated with the decreased
      repopulating ability of HSPC in vivo and diminished hematopoietic activity in
      bone marrow cultures treated with nicotine. Interestingly, nicotine stimulated
      the production of IL4 and IL5, implying a possible role of the cholinergic system
      in pathogenesis of allergic diseases. Our data provide evidence that the nicotine
      induced imbalance of the cholinergic system during gestation interferes with
      normal development and provides the basis for negative health outcomes postpartum
      in active and passive smokers.

PMID- 17512957
TI  - Short-term effects of changes in water management on the limnological
      characteristics and zooplankton of a eutrophic Mediterranean coastal lagoon (NE
      Iberian Peninsula).
AB  - The Ter Vell (NE Iberian Peninsula) is a eutrophic coastal lagoon which has been
      flooded by the excess irrigation water and the agricultural runoff during the
      last decades. Between 1999 and 2003, restoration measures were applied to improve
      its water quality. At the same time, but independently, agricultural water
      management drastically reduced the freshwater inflow. The short-term effects of
      these management actions on the limnological characteristics of the lagoon were
      analysed by comparing two hydrological cycles, one before (1999/2000) and the
      other one after (2002/2003) the actions. The two cycles are illustrative of
      opposite situations in the hydrological functioning of coastal wetlands. In the
      first, the lagoon was exorheic, with prolonged flooding periods and a low
      residence time; in the second, it had a more endorheic character, with scarce
      water inputs and prolonged periods of confinement. Consequently, nitrogen inputs
      diminished and organic load and salinity increased as the internal loading and
      the accumulation effects became more relevant. These effects were actually caused
      by the drastic reduction in the freshwater inflow which prevented, in turn, the
      success of the restoration measures. The zooplankton community of the Ter Vell
      lagoon was not significantly altered by the hydrological change, at least in the
      short-term, and rotifers and cladocerans, mainly those species indicative of
      eutrophy, dominated the community.

PMID- 17512958
TI  - Site-specific success of three transplanting methods and the effect of planting
      time on the establishment of Zostera marina transplants.
AB  - Eelgrass, Zostera marina, is the most abundant seagrass species on the coast of
      Korea, but most large eelgrass meadows have disappeared since the 1970s due to
      human-induced disturbance. To restore disturbed seagrass habitats in die-off
      areas, seagrass transplanting has been attempted using various methods. Here, we
      assessed the feasibility and efficiency of seagrass transplanting methods
      depending on the sediment type at the planting site. Additionally, the effect of
      planting time on the establishment of transplant was examined to determine the
      optimal season for planting. We conducted an eelgrass transplanting experiment
      from fall 2003 to summer 2004 at three sites with different sediment types using
      three planting techniques. The staple method resulted in the highest transplant
      survival rate (77.1-93.8%) at all three sites, but was labor intensive.
      Transplanting Eelgrass Remotely with Frame Systems (TERFS) method also resulted
      in relatively a high survival rate (58.7-69.0%) at all sites. The shell method is
      a newer eelgrass transplanting method in which oyster shells are used as an
      anchoring device, and does not require SCUBA diving for subtidal transplanting.
      The shell method resulted in high survival rates in muddy (81.3%) and silty
      sediments (76.5%), but remarkably low survival rate in sandy sediments (5.0%).
      The TERFS, and shell methods reduced underwater labor; thus, these methods is
      suitable for large-scale seagrass restoration. Eelgrass transplants planted in
      summer had exhibited significant mortality due to high summer water temperatures.
      Although transplants planted in fall to spring had relatively high survival
      rates, transplanting and collection of vegetative shoots are difficult in winter
      and spring. Therefore, fall was suggested as the most effective transplanting
      season off the coast of Korea.

PMID- 17512960
TI  - A novel mouse model for assessment of male sexual function.
AB  - A novel model to evaluate erectile, ejaculatory, and sexual behavior patterns in
      conscious mouse is presented. Corpus spongiosum of the penis (CSP) pressure was
      recorded by using telemetry and was correlated with erectile activity (penile
      elongations, cups, flips) during reflex induction and spontaneous erections in
      freely moving mice. CSP pressure was also recorded during mating tests (mounts,
      intromissions with erections, ejaculations), as well as non-contact tests with
      estrous female mice. Erectile events were quantified in four sexual contexts
      (spontaneous erections, spinal reflexes, in mating and non-contact tests). The
      data demonstrate that CSP pressure monitoring is a valid technique for assessment
      of sexual function in freely moving mice.

PMID- 17512961
TI  - Vitamin B biosynthesis in plants.
AB  - The vitamin B complex comprises water-soluble enzyme cofactors and their
      derivatives that are essential contributors to diverse metabolic processes in
      plants as well as in animals and microorganisms. Seven vitamins form this
      complex: B1 (thiamin (1)), B2 (riboflavin (2)), B3 (niacin (3)), B5 (pantothenic
      acid (4)), B6 (pyridoxine, pyridoxal (5), and pyridoxamine), B8 (biotin (6)), and
      B9 (folate (7)). All seven B vitamins are required in the human diet for proper
      nutrition because humans lack enzymes to synthesize these compounds de novo. This
      review aims to summarize the present knowledge of vitamin B biosynthesis in
      plants.

PMID- 17512959
TI  - Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet.
AB  - Diets high in fat or protein and extremely low in carbohydrate are frequently
      reported to result in weight loss in humans. We previously reported that rats
      maintained on a low-carbohydrate-high fat diet (LC-HF) consumed similar kcals/day
      as chow (CH)-fed rats and did not differ in body weight after 7 weeks. LC-HF rats
      had a 45% decrease in POMC expression in the ARC, decreased plasma insulin, and
      increased plasma leptin and ghrelin. In the present study we assessed the effects
      of a low-carbohydrate-high-protein diet (HP: 30% fat, 65% protein, and 5% CHO) on
      body weight, caloric intake, plasma hormone levels and hypothalamic gene
      expression. Male rats (n=16) were maintained on CH or HP for 4 weeks. HP rats
      gained significantly less weight than CH rats (73.4+/-9.4 and 125.0+/-8.2 g) and
      consumed significantly less kcals/day (94.8+/-1.5 and 123.6+/-1.1). Insulin was
      significantly reduced in HP rats (HP: 1.8+/-0.6 vs. CH: 4.12+/-0.8 ng/ml), there
      were no differences between groups in plasma leptin and plasma ghrelin was
      significantly elevated in HP rats (HP: 127.5+/-45 vs. CH: 76.9+/-8 pg/ml).
      Maintenance on HP resulted in significantly increased ARC POMC (HP: 121+/-10.0
      vs. 100+/-5.9) and DMH NPY (HP: 297+/-82.1 vs. CH: 100+/-37.7) expression
      compared to CH controls. These data suggest that the macronutrient content of
      diets differentially influences hypothalamic gene expression in ways that can
      affect overall intake.

PMID- 17512963
TI  - Pharmacokinetics and nephrotoxicity of aristolochic acid in rabbits.
AB  - Aristolochic acids (AAs) which exist in plants of the genus Aristolochia are the
      toxins responsible for aristolochic acid nephropathy (AAN). To investigate the
      pharmacokinetics and nephrotoxicity of AAs, rabbits were used in this study. The
      plasma concentrations of the main components of AAs, aristolochic acid I (AA I)
      and aristolochic acid II (AA II), were determined by a validated high-performance
      liquid chromatographic method. After intravenous administration of different
      doses (0.25, 0.5, 1.0, and 2.0mg/kg) of aristolochic acid sodium (AANa) to 4
      respective groups of rabbits (n=6 for each dose), linear relationships between
      the doses of AA I and AA II and the area under the plasma concentration curve
      (AUC) were found to exist (p<0.001). AANa was also given in escalating doses
      (0.5, 1.0, and 2.0mg/kg) to the same rabbits at 7-day intervals. The clearance
      rates of both AA I and AA II significantly decreased with the escalating dose
      (p<0.001). A nonlinear relationship between the dose and AUC was obtained. Kidney
      specimens of rabbits were obtained to observe morphological changes on days 1 and
      7 after AANa administration. The renal lesions caused by AAs consisted of
      progressive and dose-dependent tubular damage. However, no remarkable changes in
      the morphology of glomeruli were observed.

PMID- 17512962
TI  - Gene expression profiling and differentiation assessment in primary human
      hepatocyte cultures, established hepatoma cell lines, and human liver tissues.
AB  - Frequently, primary hepatocytes are used as an in vitro model for the liver in
      vivo. However, the culture conditions reported vary considerably, with associated
      variability in performance. In this study, we characterized the differentiation
      character of primary human hepatocytes cultured using a highly defined, serum
      free two-dimensional sandwich system, one that configures hepatocytes with
      collagen I as the substratum together with a dilute extracellular matrix
      (Matrigeltrade mark) overlay combined with a defined serum-free medium containing
      nanomolar levels of dexamethasone. Gap junctional communication, indicated by
      immunochemical detection of connexin 32 protein, was markedly enhanced in
      hepatocytes cultured in the Matrigel sandwich configuration. Whole genome
      expression profiling enabled direct comparison of liver tissues to hepatocytes
      and to the hepatoma-derived cell lines, HepG2 and Huh7. PANTHER database analyses
      were used to identify biological processes that were comparatively over
      represented among probe sets expressed in the in vitro systems. The robustness of
      the primary hepatocyte cultures was reflected by the extent of unchanged
      expression character when compared directly to liver, with more than 77% of the
      probe sets unchanged in each of the over-represented categories, representing
      such genes as C/EBPalpha, HNF4alpha, CYP2D6, and ABCB1. In contrast, HepG2 and
      Huh7 cells were unchanged from the liver tissues for fewer than 48% and 55% of
      these probe sets, respectively. Further, hierarchical clustering of the
      hepatocytes, but not the cell lines, shifted from donor-specific to treatment
      specific when the probe sets were filtered to focus on phenobarbital-inducible
      genes, indicative of the highly differentiated nature of the hepatocytes when
      cultured in a highly defined two-dimensional sandwich system.

PMID- 17512964
TI  - Novel RDH12 mutations associated with Leber congenital amaurosis and cone-rod
      dystrophy: biochemical and clinical evaluations.
AB  - The purpose of this study was to determine the role of the retinol dehydrogenase
      12 (RDH12) gene in patients affected with Leber congenital amaurosis (LCA),
      autosomal recessive retinitis pigmentosa (arRP) and autosomal dominant/recessive
      cone-rod dystrophies (CORD). Changes in the promoter region, coding regions and
      exon/intron junctions of the RDH12 gene were evaluated using direct DNA
      sequencing of patients affected with LCA (n=36 cases), RP (n=62) and CORD (n=21).
      The allele frequency of changes observed was assessed in a multiethnic control
      population (n=159 individuals). Detailed biochemical and structural modeling
      analysis of the observed mutations were performed to assess their biological role
      in the inactivation of Rdh12. A comprehensive clinical assessment of retinal
      structure and function in LCA patients carrying mutations in the RDH12 gene was
      completed. Of the six changes identified, three were novel including a homozygous
      C201R change in a patient affected with LCA, a heterozygous A177V change in
      patients affected with CORD and a heterozygous G46G change in a patient affected
      with LCA. A novel compound heterozygote T49M/A269fsX270 mutation was also found
      in a patient with LCA, and both homozygous and heterozygous R161Q changes were
      seen in 26 patients affected with LCA, CORD or RP. These R161Q, G46G and the
      A177V sequence changes were shown to be polymorphic. We found that Rdh12 mutant
      proteins associated with LCA were inactive or displayed only residual activity
      when expressed in COS-7 and Sf9 cells, whereas those mutants that were considered
      polymorphisms were fully active. Thus, impairment of retinal structure and
      function for patients carrying these mutations correlated with the biochemical
      properties of the mutants.

PMID- 17512965
TI  - The different mechanisms of the motion direction illusion and aftereffect.
AB  - Direction repulsion is the illusory expansion of the angle between two directions
      of motion, and may occur when the two directions are presented simultaneously (an
      illusion) or successively (an aftereffect). Here we demonstrate that the motion
      direction illusion (DI) and aftereffect (DAE) have different mechanisms. Two
      experiments show that when the two interacting stimuli are presented to different
      eyes, the DI is greatly reduced but the DAE is obtained at near to full strength.
      These results suggest that different populations of cells within the visual
      pathway produce the DI and DAE.

PMID- 17512967
TI  - Coagulation characteristics of humic acid modified with glucosamine or taurine.
AB  - To suppress the coagulation of humic acid (HA) in aqueous solutions, HA was
      modified with hydrophilic amines, such as glucosamine or taurine. These amines
      were attached to carboxyl groups in HA via amide bond formation. The degree of
      modification (R(m)) was estimated to be 21-38%. Infrared spectra of the modified
      HAs were also consistent with the presence of amide bonds. Acid-base titration
      showed that the average acid-dissociation constant (pK(app)) of the HA samples
      was increased by the modification. The Ca(2+) binding capacity of HA decreased
      with an increase in R(m) value. Critical pH or Ca(2+) concentration, at which HA
      coagulation occurs, was increased as the result of the modification. These
      critical points for taurine-HA were higher than those for glucosamine-HA. This is
      mainly due to electrostatic repulsion by sulfonate groups in taurine. These
      results indicate that the coagulation of HA is suppressed by modifying the
      molecules with glucosamine or taurine.

PMID- 17512966
TI  - Structure-based discovery of a new class of Bcl-xL antagonists.
AB  - Apoptosis, or programmed cell death, plays a key role in normal tissue
      homeostasis ensuring a proper balance between cell production and cell loss. Anti
      apoptotic Bcl-2-family proteins are central regulators of the apoptotic pathway
      and due to their ability to confer tumor resistance to chemotherapy or radiation,
      have been recently validated as targets for cancer drug discovery. Since the
      crucial interaction between pro- and anti-apoptotic members occurs via a
      conserved region located on the surface of the protein, a viable way to inhibit
      the anti-death activity of Bcl-2 proteins is to design small molecule inhibitors
      that occupy this cavity. Here, we describe a structure-based approach that led to
      the identification of four small molecule inhibitors directed at the hydrophobic
      groove on the surface of the Bcl-2 family protein Bcl-xL. The compounds were
      characterized in a number of assays including in vitro binding using 15N-labeled
      protein, a displacement DELFIA assay, and a cell-based viability assay with human
      cancer cells.

PMID- 17512968
TI  - Modelling of PCDD/F release from MSW bio-drying.
AB  - In the present work, an experimentation was carried out to study the behaviour of
      PCDD/F during the process of municipal solid waste (MSW) bio-drying. This process
      belongs to the biological mechanical treatment (BMT) options and is aimed to the
      dewatering of MSW thanks to the biological exothermal reactions (thermal drying,
      on the contrary, needs an external heat source as methane). The result is a
      decrease of waste weight and an increase of lower heating value (as the energy
      content refers to a lower amount of waste). Of course, the overall energy
      availability does not increase, but the characteristics of bio-drying are
      interesting as a way for refuse derived fuel generation: glass, metals and inert
      removals are easier after bio-drying. The literature of the sector shows only few
      data on PCDD/F emission to air from BMT. Anyway, in the present work an original
      theory has been put forward in order to explain the enrichment of PCDD/F in the
      air exiting the biological processes. The role of the initial PCDD/F
      concentration in the ambient air entering the plant is obviously taken into
      account. The results of the developed experimentation and the following
      elaborations point out that PCDD/F could be freed from the volatile solids
      consumed during the process. The different amount of PCDD/F in the waste and the
      different consumption of volatile solids depending on the biological process can
      explain the different PCDD/F emission factors available in the literature.

PMID- 17512969
TI  - Comparison of in vitro and in vivo acute fish toxicity in relation to toxicant
      mode of action.
AB  - Acute toxicity to fish hepatoma cell line PLHC-1 and to juvenile rainbow trout
      was examined for 18 plant protection products. The main objective was to explore
      whether hepatoma cells could be used to predict acute toxicity in fish taking
      into account the mode of toxic action and compound properties. Acute fish
      toxicity was determined using the OECD guideline test 203 and compared to
      predicted baseline LC50 of acute fish toxicity calculated with a quantitative
      structure-activity relationship (QSAR) derived for guppy fish. Cytotoxicity was
      determined through the inhibition of neutral red uptake (NR(50)) into lysosomes
      and compared to predicted baseline cytotoxicity derived for goldfish GFS cells.
      In general, NR50 values were higher by a factor ranging from 3 to 3000 than the
      corresponding acute LC50. A weak correlation between NR50 and LC50 values was
      found (log/log: r2=0.62). Also the lipophilicity (log K(ow)) was not a good
      predictor for cytotoxicity (r2=0.43) and lethality (r2=0.57) of these pesticides.
      The neutral red assay is detecting general baseline toxicity only. Comparing LC50
      data to QSAR results, the compounds can be classified to act as narcotics or
      reactive compounds with a specific mode of toxic action in fish. The results
      indicate that limitation of the neutral red assay in predicting acute fish
      toxicity. A promising alternative might be the assessment of toxicity in a set of
      in vitro systems addressing also cell-specific functions which are related to the
      mode of toxic action of the compound.

PMID- 17512970
TI  - Body mass distribution and gait mechanics in fat-tailed dwarf lemurs
      (Cheirogaleus medius) and patas monkeys (Erythrocebus patas).
AB  - Most quadrupeds walk with lateral sequence (LS) gaits, where hind limb touchdowns
      are followed by ipsilateral forelimb touchdowns. Primates, however, typically
      walk with diagonal sequence (DS) gaits, where hind limb touchdowns are followed
      by contralateral forelimb touchdowns. Because the use of DS gaits is nearly
      ubiquitous among primates, understanding gait selection in primates is critical
      to understanding primate locomotor evolution. The Support Polygon Model [Tomita,
      M., 1967. A study on the movement pattern of four limbs in walking. J. Anthropol.
      Soc. Nippon 75, 120-146; Rollinson, J., Martin, R.D., 1981. Comparative aspects
      of primate locomotion, with special reference to arboreal cercopithecines. Symp.
      Zool. Soc. Lond. 48, 377-427] argues that primates' use of DS gaits stems from a
      more caudal position of the whole-body center of mass (COM) relative to other
      mammals. We tested the predictions of the Support Polygon Model by examining the
      effects of natural and experimental variations in COM position on gait mechanics
      in two distantly related primates: fat-tailed dwarf lemurs (Cheirogaleus medius)
      and patas monkeys (Erythrocebus patas). Dwarf lemur experiments compared
      individuals with and without a greatly enlarged tail (a feature associated with
      torpor that can be expected to shift the COM caudally). During patas monkey
      experiments, we experimentally shifted the COM cranially with the use of a
      weighted belt (7-12% of body mass) positioned above the scapulae. Examination of
      limb kinematics revealed changes consistent with systematic deviations in COM
      position. Nevertheless, footfall patterns changed in a direction contrary to the
      predictions of the Support Polygon Model in the dwarf lemurs and did not change
      at all in the patas monkey. These results suggest that body mass distribution is
      unlikely to be the sole determinant of footfall pattern in primates and other
      mammals.

PMID- 17512971
TI  - Long-term decline of 137Cs concentration in honey in the second decade after the
      Chernobyl accident.
AB  - In the years 2001-2004 the (137)Cs activity was investigated in a total of 336
      samples of different varieties of honey harvested in the Liguria Region of
      Northern Italy. Our purpose was to define (a) residual radioactive contamination
      following the Chernobyl accident and (137)Cs long-term decline, (b) correlation
      between (137)Cs activity and different honey varieties, and (c) correlation
      between (137)Cs activity and the prevailing geomorphological configuration in the
      collection areas. The mean (137)Cs specific activity was 4.33+/-5.04 S.D. Bq/kg.
      Chestnut honey showed higher levels of radioactive contamination, which were
      ascribed to the extensive, superficial and deep, root apparatus of the tree.
      Honey samples from acidic argillite soils, which withhold radionuclides after
      deposition and slowly release them to plants, also showed higher (137)Cs
      activity. Long-term decline was calculated at 456 days, a value lower than those
      published from different food sources in the years following the accident. The
      rate of long-term decline decreases with time.

PMID- 17512972
TI  - Defining the sources of low-flow phosphorus transfers in complex catchments.
AB  - Nutrient transfers from the land to rivers have the potential to cause persistent
      eutrophic impacts at low flows even though the transfers may constitute a minor
      percentage of total annual fluxes. In rural catchments, the contribution from
      agricultural soils during storm events can be particularly large and untangling
      the relative contributions from multiple sources that vary in time and space is
      especially problematic. In this study, the potential for domestic septic tank
      system pollution during low flows was investigated in 3 small catchments (3 to 5
      km(2)) using an integrated series of methods. These included septic system
      surveys, continuous (10 min) total phosphorus (TP) monitoring at the outlet of
      each catchment, repeated low-flow water quality surveys in sub-catchments
      upstream of the catchment outlets and single day river-walk water quality
      surveys. A series of faecal matter and grey-water fingerprinting techniques were
      also employed. These included determining sterol ratios in stream sediments,
      monitoring the presence of proteins, E. coli and enterococci bacterial signatures
      and boron. The total density and density of poorly maintained septic systems
      mirrored the magnitude of frequent TP concentrations in the catchments although
      this relationship was less apparent in the nested sub-catchments. The exception
      was possibly related to the simple hydraulics in one particular catchment and
      indicated temporary effluent attenuation in the other catchments. Repeated low
      flow and river-walk water quality surveys highlighted discrete areas and reaches
      where stepped changes in nutrient concentration occurred. Bio-chemical
      fingerprinting showed that between 7% and 27% of sediments were contaminated with
      human faecal material and correlation matrices indicated that, at least during
      low flows, P fractions were positively correlated with some markers of faecal and
      grey-water contamination.

PMID- 17512973
TI  - VEGF increases the fibrinolytic activity of endothelial cells within fibrin
      matrices: involvement of VEGFR-2, tissue type plasminogen activator and matrix
      metalloproteinases.
AB  - Proteolysis of fibrin matrices by endothelial cells plays essential roles in the
      migratory and morphogenic differentiation processes underlying angiogenesis.
      Using an in vitro fibrinolysis model consisting of human umbilical vein
      endothelial cells (HUVECs) embedded in a three dimensional fibrin matrix, we show
      that VEGF, an angiogenic cytokine that plays a crucial role in the onset of
      angiogenesis, is a potent activator of HUVEC-mediated fibrinolysis. This VEGF
      dependent fibrin degradation was completely abrogated by inhibitors of either the
      plasminogen activator/plasmin or matrix metalloproteinases (MMP) proteolytic
      systems, suggesting the involvement of both classes of proteases in fibrin
      degradation. Accordingly, VEGF-induced fibrinolysis correlated with an increase
      in the expression of tPA and of some MMPs, such as MT2-MMP and was completely
      blocked by a neutralizing antibody against tPA. Overall, these results indicate
      that efficient proteolysis of three dimensional fibrin matrices during VEGF
      mediated angiogenesis involves a complex interplay between the MMP and plasmin
      mediated proteolytic systems.

PMID- 17512974
TI  - Involvement of 5-HT1A and GABAA receptors in the anxiolytic-like effects of
      Cinnamomum cassia in mice.
AB  - An elevated plus maze (EPM) test was used to determine if the 5-HT1A, GABAA, and
      benzodiazepine receptors play a role in the anxiolytic-like effects of a 50% EtOH
      extract of Cinnamomum cassia (C. cassia) in mice. A single treatment with C.
      cassia (750 mg/kg, p.o.) significantly increased the number of entries into and
      the time spent in the open arms of the EPM compared with the controls. A repeated
      treatment with C. cassia (100 mg/kg, 5 days, p.o.) significantly increased the
      time spent in the open arms of the EPM. Moreover, WAY 100635, (+)-bicuculline,
      and flumazenil blocked the effect of C. cassia. However, there were no changes in
      the locomotor activity and horizontal wire test observed in any group compared
      with the controls. Taken together, these results show that C. cassia has no
      adverse effects, such as myorelaxant effects, and might be an effective
      anxiolytic agent by regulating the serotonergic and GABAergic system.

PMID- 17512975
TI  - Prevalence of smoking and associated factors among pregnant women in Japan.
AB  - OBJECTIVE: This study was conducted to estimate the prevalence of smoking among
      pregnant women living in Japan and to analyze the factors associated with their
      smoking behavior. METHOD: Five hundred institutions with maternity services were
      randomly sampled from a list of the Japan Association of Obstetricians and
      Gynecologists. Of these institutions, 260 participated in the survey which was
      conducted in February 2002. Using a self-reported anonymous questionnaire, a
      survey on smoking behavior, drinking behavior and sleep status was conducted on
      pregnant women. Chi-square tests and logistic regression analyses were used to
      examine the factors associated with their smoking behavior. RESULTS: Data were
      obtained from a total of 16,414 pregnant women. The prevalence of smoking during
      pregnancy was 9.9% [95% confidence interval (CI) 9.4%, 10.4%]. The quit rate of
      smoking among pregnant woman was 61.9% [95% CI 60.4%, 63.4%]. The odds ratios for
      smoking during pregnancy were significantly higher in women with relatively young
      age, less schooling, multiparous, exposure to passive smoking, short sleep
      duration and in women who drank. CONCLUSION: Smoking among pregnant women remains
      an important public health problem in Japan. It is necessary to promote
      antismoking measures based on the results of this study.

PMID- 17512976
TI  - Overview of sexing sperm.
AB  - Hundreds of thousands of off springs have been born as a result of AI with sexed
      sperm. Although this technology has been used for many species, the overwhelming
      majority of pregnancies have been in cattle, nearly all as a result of sperm that
      were sexed and subsequently frozen. The technology for sexing sperm has not
      changed greatly in the past 7 years, but refinements have speeded up the process
      and reduced damage to sperm. The process of commercialization of sexed sperm has
      accelerated recently. However, this technology is characterized by high costs,
      complexity of implementation and lower pregnancy rates than with control sperm.
      Nevertheless, sexed, frozen bovine sperm are being produced commercially in many
      countries, although from a limited number of bulls. The main application of sexed
      sperm to date has been to breed dairy heifers to produce female calves. Because
      of the slow speed of sexing sperm, fewer sperm are used per insemination dose of
      sexed than conventional sperm, and pregnancy rates with this product are often
      only slightly decreased. Successful use of sexed sperm requires excellent
      management of cattle, careful handling of sperm and use of skilled inseminators.
      As costs decline, sexed sperm will be used increasingly for cattle breeding,
      horse breeding and niche applications in other species.

PMID- 17512977
TI  - Proteomic study of the establishment of boar epididymal cell cultures.
AB  - A proteomic approach was used in this study to follow the protein expression of
      epididymal cells during the different phases of a cell culture protocol which was
      able to obtain an epididymal cell monolayer. The secretory activity of intact
      proximal and middle caput epididymal fragments and caput, corpus and cauda
      epithelial cell monolayers was examined on different days of culture.
      Transcriptomic activity was also followed by RT-PCR for the mRNA of several
      previously identified major proteins. During the establishment of epididymal cell
      cultures, a progressive shift was found in the pattern of protein secretion. The
      normal epididymal protein profile, specific for each epididymal region, was
      progressively replaced by a less specific profile with the secretion of new
      proteins. A correlation between protein secretion and the presence of the mRNA of
      the marker proteins was observed only in the first phase of culture. Most of the
      new proteins which appeared were characteristic of the secretion of cell
      monolayers cultivated over several weeks. Despite the significant modifications
      of the epididymal cell secretome, the presence of new proteins secreted only by
      cell cultures originating from a specific epididymal region shows the presence of
      remaining endogenous differentiation.

PMID- 17512978
TI  - Characteristics of seminal plasma proteins and their correlation with canine
      semen analysis.
AB  - The objectives were to separate canine seminal plasma proteins (with SDS-PAGE)
      and to determine the correlation between specific proteins and semen
      characteristics. Three ejaculates from 20 mixed-breed dogs, of unknown fertility,
      were collected by digital manipulation. Ejaculate volume and color, sperm
      motility, sperm vigor, percentage of morphologically normal spermatozoa, and
      membrane integrity (hypoosmotic swelling test and fluorescent staining) were
      assessed. For each dog, seminal plasma was pooled from all three ejaculates and
      proteins were separated with SDS-PAGE, using polyacrylamide concentrations of 13%
      and 22% in the separation gels. After staining, gel images were digitized to
      estimate molecular weights (MW) and integrated optical density (IOD) of each lane
      and of individual bands. Total seminal plasma protein concentration was 2.19+/
      1.56 g/dL (mean+/-SD; range 1.12-5.19 g/dL). A total of 37 protein bands were
      identified (although no dog had all 37 bands). In the 13% gel, molecular weights
      ranged from 100.6 to 17.1 kDa, with four bands (49.7, 33.2, 26.4, and 19.5 kDa)
      present in samples from all dogs. In the 22% gel, molecular weights ranged from
      15.6 to 3.6 kDa, with nine bands (15.6, 13.5, 12.7, 11.7, 10.5, 8.7, 7.8, 5.6,
      and 4.9 kDa) present in samples from all dogs. Combined for both gels, the
      majority of bands (85%) had molecular weights <17 kDa, with B20 (15.6 kDa) in
      high concentrations in samples from all dogs. There were positive correlations (P
      < or = 0.01) between two bands, B4 (67 kDa) and B5 (58.6 kDa), and sperm motility
      (r=0.66 and r=0.46), sperm vigor (r=0.56 and r=0.66), percentage of
      morphologically normal spermatozoa (r=0.55 and r=0.59), the hypoosmotic swelling
      test (r=0.76 and r=0.68), and fluorescent staining (r=0.56 and r=0.59),
      respectively. In conclusion, 37 proteins were identified in seminal plasma; two
      were significantly correlated with semen characteristics.

PMID- 17512979
TI  - Peritoneal adhesion prevention with an in situ cross-linkable hyaluronan gel
      containing tissue-type plasminogen activator in a rabbit repeated-injury model.
AB  - Postoperative peritoneal adhesions can have serious, potentially lethal
      consequences. Pharmacotherapy and barrier devices can reduce adhesion formation
      to varying degrees, but their efficacy is limited by rapid clearance from the
      peritoneum and lack of biological activity, respectively. To overcome these
      limitations, we have delivered tissue-type plasminogen activator (tPA), which is
      deficient in the first 2-3 postoperative days, using a highly cross-linked in
      situ forming hyaluronan gel (HAX(hx)). We demonstrated this formulation's anti
      adhesion activity in a rigorous animal model that involved recurrent adhesions.
      While non-treated or saline-treated animals developed widespread adhesions
      (frequency, both 100%; median adhesion area, 12.7 and 15.4 cm(2), respectively),
      tPA delivered by HAX(hx) (tPA-HAX(hx)) was highly effective in preventing
      recurrent adhesions (frequency, 44%; median adhesion area, 0.1cm(2)). HAX(hx)
      itself, tPA solution, and inactivated tPA in HAX(hx) did not provide comparable
      anti-adhesion activity. tPA-HAX(hx) is a system that is easy to use and
      potentially promising for adhesion prevention.

PMID- 17512980
TI  - Comparing methods of quantifying diplopia.
AB  - PURPOSE: Quantification of diplopia is important for describing severity of
      strabismus, measuring change over time, and reporting surgical outcomes. The
      cervical range of motion (CROM) method has been proposed as a simple, inexpensive
      alternative to the Goldmann perimeter for quantifying diplopia. The purpose of
      this study was to compare these 2 techniques and describe advantages and
      disadvantages. DESIGN: Cohort study. PARTICIPANTS: Seventy-six consecutive
      patients with binocular diplopia associated with any type of strabismus. METHODS:
      Patients underwent diplopia assessment with the CROM method and Goldmann
      perimeter; diplopia was scored between 0 and 100 based on previously published
      scoring systems. Where CROM and Goldmann results were disparate by >20 points,
      the medical record was reviewed independently by 2 clinicians to determine the
      most likely reason for the discrepancy. MAIN OUTCOME MEASURES: (1) Measure of
      agreement between diplopia scores using the CROM and Goldmann methods using the
      kappa test and (2) the reasons for any disagreement between tests of >20 points.
      RESULTS: Overall agreement between the 2 tests was good (intraclass correlation
      coefficient, 0.65; 95% confidence interval, 0.50-0.77). In 49 (64%) of 76 tests,
      the CROM and Goldmann results were within 20 points. Of the 27 (36%) showing a
      more than 20-point discrepancy, 17 were worse using the Goldmann technique and 10
      were worse using the CROM technique. The most frequent reason for worse diplopia
      using the Goldmann technique was poorer ability to fuse or suppress in the
      Goldmann apparatus compared with the real-world targets used in free space for
      the CROM method. Worse diplopia using the CROM method most often was the result
      of the deviation being present for distance only. In some cases, differences were
      the result of the greater weighting of primary position using the current scoring
      system for the CROM method. CONCLUSIONS: In most cases, the CROM and Goldmann
      methods provide equivalent measures of diplopia severity. However, the Goldmann
      method seems to overestimate diplopia in patients with fragile fusion or tenuous
      suppression and seems to underestimate diplopia in deviations present for
      distance only. The CROM method may be more representative of diplopia severity as
      experienced in everyday life.

PMID- 17512981
TI  - Anticonvulsant effects of damage to structures involved in seizure induction in
      rats exposed to soman.
AB  - In nerve agent research, it is assumed that the regions from which seizure
      activity is triggered may offer clues for the designing of effective
      anticonvulsive therapy. In the present study, selective brain lesions were made
      to identify critical cholinergic pathways and seizure controlling areas involved
      in the induction of epileptiform activity in rats challenged with soman. The
      results showed that rats with bilateral aspiration lesion of the seizure
      controlling substrate, area tempestas (AT) in the piriform cortex, displayed
      marked anticonvulsant effects, whereas such effects were not seen when substantia
      nigra was destroyed. Aspiration lesion of the medial septal area (MS) including
      the vertical limb of the diagonal band nucleus (DBN) caused increased latency to
      the onset of convulsions, whereas damage to the nucleus basalis magnocellularis
      (NBM), nucleus accumbens, or both MS and NBM did not cause anticonvulsant
      effects. Saporin lesion of MS, DBN (horizontal limb), or MS+DBN had no
      anticonvulsant effects, suggesting that aspiration lesion of MS disrupted
      pathways beyond cholinergic ones. Severe aphagia/adipsia and reduced body weight
      occurred in rats with lesions in the septal area. In separate sham operated rats,
      a strong positive correlation was found between body weight and latency to onset
      of convulsions in response to soman. Thus, weight loss and a relatively high dose
      of soman (1.6 x LD(50)) in this context may have masked potential anticonvulsant
      effects among some lesioned animals. It is inferred that MS and AT/piriform
      cortex occur as prime target areas for induction of seizures by soman.

PMID- 17512982
TI  - Developmental exposure to pesticides zineb and/or endosulfan renders the
      nigrostriatal dopamine system more susceptible to these environmental chemicals
      later in life.
AB  - Several epidemiological studies have suggested a role for environmental pesticide
      exposures in idiopathic Parkinson's disease. The purpose of this study was to
      test the hypothesis that exposure to pesticides such as endosulfan and/or zineb
      during critical periods of postnatal development could result in neuronal
      dysfunction and enhance the impact of these pesticides during exposure as adults.
      C57BL/6 mice, exposed daily to each of the pesticides or their mixtures from
      postnatal days 5 to 19, exhibited insignificant changes in striatal dopamine,
      acetylcholinesterase and alpha-synuclein levels. However, mice exposed to these
      pesticides as juveniles and re-exposed at 8 months of age had significantly
      altered striatum and brain cortex neurotransmitter levels. Thus, mice re-exposed
      during adulthood to zineb, endosulfan and their mixtures showed a significantly
      depleted striatal dopamine levels, to 22, 16 and 35% of control, respectively.
      Acetylcholinesterase activity in the cerebral cortex was significantly increased
      in all pesticide treated groups (rho< or =0.05) upon repeated exposure, and
      pesticide mixture treatment also significantly increased levels of normal and
      aggregated alpha-synuclein. Collectively, these findings support our hypothesis
      that exposure to pesticides such as endosulfan and zineb during critical periods
      of postnatal development contributes to neurotransmitter changes upon re
      challenge in adulthood.

PMID- 17512984
TI  - Mitochondrial mechanisms of estrogen neuroprotection.
AB  - Oxidative stress, bioenergetic failure and mitochondrial dysfunction are all
      implicated in the etiology of neurodegenerative diseases such as Alzheimer's
      disease (AD). The mitochondrial involvement in neurodegenerative diseases
      reflects the regulatory role mitochondrial failure plays in both necrotic cell
      death and apoptosis. The potent feminizing hormone, 17 beta-estradiol (E2), is
      neuroprotective in a host of cell and animal models of stroke and
      neurodegenerative diseases. The discovery that 17alpha-estradiol, an isomer of
      E2, is equally as neuroprotective as E2 yet is >200-fold less active as a
      hormone, has permitted development of novel, more potent analogs where
      neuroprotection is independent of hormonal potency. Studies of structure-activity
      relationships and mitochondrial function have led to a mechanistic model in which
      these steroidal phenols intercalate into cell membranes where they block lipid
      peroxidation reactions, and are in turn recycled. Indeed, the parental estrogens
      and novel analogs stabilize mitochondria under Ca(2+) loading otherwise
      sufficient to collapse membrane potential. The neuroprotective and mitoprotective
      potencies for a series of estrogen analogs are significantly correlated,
      suggesting that these compounds prevent cell death in large measure by
      maintaining functionally intact mitochondria. This therapeutic strategy is
      germane not only to sudden mitochondrial failure in acute circumstances, such as
      during a stroke or myocardial infarction, but also to gradual mitochondrial
      dysfunction associated with chronic degenerative disorders such as AD.

PMID- 17512985
TI  - Tama-kugel: hardware and software for measuring direction, distance, and velocity
      of locomotion by insects.
AB  - We have developed an accurate and inexpensive system for recording the path taken
      by a moving insect. The system consists of a low-mass ball on which the loosely
      tethered insect runs, an optical sensor to detect rotation of the ball, and
      software written in Visual Basic 6.0 that interprets and records the hardware's
      output. The ball floats on a cushion of air. The optical sensor's output is
      encoded as changes in x, y coordinates. The software monitors this output
      continually, and records each new x, y pair and the time at which it occurred.
      Since the system records only those data that have changed, the output files are
      compact. In its present form, the system is calibrated to detect changes in the
      animal's position roughly equivalent to one body length. It can accurately record
      the details of paths hundreds of meters long. We have applied the system to
      measure the paths taken by female crickets in response to male calls that differ
      in their temporal structure.

PMID- 17512983
TI  - Neurosteroid regulation of GABA(A) receptors: Focus on the alpha4 and delta
      subunits.
AB  - Neurosteroids, such as the progesterone metabolite 3alpha-OH-5alpha[beta]-pregnan
      20-one (THP or [allo]pregnanolone), function as potent positive modulators of the
      GABA(A) receptor (GABAR) when acutely administered. However, fluctuations in the
      circulating levels of this steroid at puberty, across endogenous ovarian cycles,
      during pregnancy or following chronic stress produce periods of prolonged
      exposure and withdrawal, where changes in GABAR subunit composition may occur as
      compensatory responses to sustained levels of inhibition. A number of
      laboratories have demonstrated that both chronic administration of THP as well as
      its withdrawal transiently increase expression of the alpha4 subunit of the GABAR
      in several areas of the central nervous system (CNS) as well as in in vitro
      neuronal systems. Receptors containing this subunit are insensitive to
      benzodiazepine (BDZ) modulation and display faster deactivation kinetics, which
      studies suggest underlie hyperexcitability states. Similar increases in alpha4
      expression are triggered by withdrawal from other GABA-modulatory compounds, such
      as ethanol and BDZ, suggesting a common mechanism. Other studies have reported
      puberty or estrous cycle-associated increases in delta-GABAR, the most sensitive
      target of these steroids which underlies a tonic inhibitory current. In the
      studies reported here, the effect of steroids on inhibition, which influence
      anxiety state and seizure susceptibility, depend not only on the subunit
      composition of the receptor but also on the direction of Cl(-) current generated
      by these target receptors. The effect of neurosteroids on GABAR function thus
      results in behavioral outcomes relevant for pubertal mood swings, premenstrual
      dysphoric disorder and catamenial epilepsy, which are due to fluctuations in
      endogenous steroids.

PMID- 17512986
TI  - Visuo-spatial processing in a dynamic and a static working memory paradigm in
      schizophrenia.
AB  - Recent findings suggest that the visuo-spatial sketchpad (VSSP) may be divided
      into two sub-components processing dynamic or static visual information. This
      model may be useful to elucidate the confusion of data concerning the functioning
      of the VSSP in schizophrenia. The present study examined patients with
      schizophrenia and matched controls in a new working memory paradigm involving
      dynamic (the Ball Flight Task - BFT) or static (the Static Pattern Task - SPT)
      visual stimuli. In the BFT, the responses of the patients were apparently based
      on the retention of the last set of segments of the perceived trajectory, whereas
      control subjects relied on a more global strategy. We assume that the patients'
      performances are the result of a reduced capacity in chunking visual information
      since they relied mainly on the retention of the last set of segments. This
      assumption is confirmed by the poor performance of the patients in the static
      task (SPT), which requires a combination of stimulus components into object
      representations. We assume that the static/dynamic distinction may help us to
      understand the VSSP deficits in schizophrenia. This distinction also raises
      questions about the hypothesis that visuo-spatial working memory can simply be
      dissociated into visual and spatial sub-components.

PMID- 17512987
TI  - Neuromyelitis optica: changing concepts.
AB  - Neuromyelitis optica (NMO; Devic's disease) and the NMO spectrum disorders are
      idiopathic inflammatory demyelinating disorders that affect the central nervous
      system and have a predilection for optic nerves and spinal cord. The
      identification of NMO-IgG as a disease-specific marker and aquaporin 4 as the
      target antigen has renewed interest in NMO. Based on current data, we suspect
      that autoantibodies arising from peripheral B cells bind to aquaporin 4 expressed
      on astrocyte foot processes on the abluminal surface of microvessels, activate
      complement and initiate inflammatory demyelination and necrosis. The development
      of animal models and further analysis of the association of NMO-IgG with disease
      severity and treatment response will elucidate the pathobiology of NMO.

PMID- 17512988
TI  - Quantitation of intrathecal antibodies in cerebrospinal fluid of subacute
      sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis:
      discrimination between microorganism-driven and polyspecific immune response.
AB  - The detection of intrathecal antibody synthesis by qualitative methods or the
      Antibody-Index (AI) is a relevant tool for diagnosis of inflammatory neurological
      diseases. An increased AI can be observed for a causative antigen as well as part
      of a polyspecific immune response. The quantitation of the intrathecal antibody
      fraction in cerebrospinal fluid (CSF), F(S), helps to discriminate both cases. In
      contrast to AI, F(S) needs an absolute antibody concentration detected in the
      ELISA in mg/L. The intrathecally synthesized, "local" antibody concentration in
      CSF (AB(Loc)) is expressed as the specific fraction of the intrathecally
      synthesized total IgG (IgG(Loc)) in CSF with F(S)=AB(Loc)/IgG(Loc) x 100 in %.
      F(S) for HSV or measles has about 20- to 60-fold higher values in virus-caused
      antibody synthesis in acute herpes simplex encephalitis (mean HSV-F(S)=8.9%) or
      subacute sclerosing panencephalitis (mean measles-F(S)=18.8%) compared to the
      polyspecific immune response against these antigens e.g., in multiple sclerosis
      (0.14% or 0.52%, correspondingly). F(S) helps also to avoid misinterpretations of
      an increasing AI in cases of therapy control, and allows direct comparison of
      relative antibody concentrations (R(S)) in blood and intrathecally synthesized
      fractions in CSF (F(S)): In multiple sclerosis patients F(S):R(S) has a mean
      ratio of about 3 for the measles, rubella and VZV antibodies. Together with the
      large variability we find by ranking that about two third of MS patients have no
      direct correlation of the relative concentrations in serum and intrathecal
      synthesis. So this concept gains increasingly relevance for analysis of the
      polyspecific immune response in brain.

PMID- 17512989
TI  - Truncated E2 of bovine viral diarrhea virus (BVDV) expressed in Drosophila
      melanogaster cells: a candidate antigen for a BVDV ELISA.
AB  - A simple and reliable indirect enzyme-linked immunosorbent assay for detection of
      antibodies directed against a major bovine viral diarrhea virus (BVDV) immunogen,
      the E2 glycoprotein (tE2-ELISA), has been developed using the recombinant C
      terminal truncated E2 glycoprotein (tE2) expressed in a Drosophila melanogaster
      system. This strategy demonstrated that tE2 is secreted efficiently in the
      supernatant, no purification steps are necessary, it is easy to produce and
      carries out the post translational modifications necessary to preserve its native
      conformation. Preliminary analysis of 183 cattle serum samples using tE2-ELISA
      showed a 98% specificity and a 100% sensitivity compared with the standard
      homologous BVDV virus neutralization test. The results also showed that the tE2
      is immunoreactive because the conformation and antigenicity of the original E2
      are maintained to a large extent. To our knowledge this is the first study report
      of the recombinant tE2 of BVDV expressed in D. melanogaster system as an antigen
      for ELISA.

PMID- 17512991
TI  - Modulation of 16S rRNA function by ribosomal protein S12.
AB  - Ribosomal protein S12 is a critical component of the decoding center of the 30S
      ribosomal subunit and is involved in both tRNA selection and the response to
      streptomycin. We have investigated the interplay between S12 and some of the
      surrounding 16S rRNA residues by examining the phenotypes of double-mutant
      ribosomes in strains of Escherichia coli carrying deletions in all chromosomal
      rrn operons and expressing total rRNA from a single plasmid-borne rrn operon. We
      show that the combination of S12 and otherwise benign mutations at positions
      C1409-G1491 in 16S rRNA severely compromises cell growth while the level and
      range of aminoglycoside resistances conferred by the G1491U/C substitutions is
      markedly increased by a mutant S12 protein. The G1491U/C mutations in addition
      confer resistance to the unrelated antibiotic, capreomycin. S12 also interacts
      with the 912 region of 16S rRNA. Genetic selection of suppressors of streptomycin
      dependence caused by mutations at proline 90 in S12 yielded a C912U substitution
      in 16S rRNA. The C912U mutation on its own confers resistance to streptomycin and
      restricts miscoding, properties that distinguish it from a majority of the
      previously described error-promoting ram mutants that also reverse streptomycin
      dependence.

PMID- 17512992
TI  - Lithium toxicity and expression of stress-related genes or proteins in A549
      cells.
AB  - To unveil some molecular mechanisms underlying lithium toxicity, expression
      changes of stress-related genes or proteins were analysed in A549 cells, cultured
      for 3 days in presence of lithium. A dose-dependent cell-growth inhibition was
      found for concentrations ranging from 2 (toxicity threshold) to 12 mM (lethality
      threshold). cDNA arrays technology was used to analyse effects of 5 and 10 mM
      lithium. Among genes involved in cell cycle regulation, proliferating cell
      nuclear antigen (PCNA) was down-regulated and cyclin kinase inhibitor p21
      (CDKN1A), up-regulated. Genes of paraoxonase 2, known to prevent LDL lipid
      peroxidation, and of catalase and SOD were found to be down-regulated whereas
      genes of cytochrome P450 (CYP2F1, CYP2E1) were up-regulated. This probably
      results in higher intracellular levels of reactive oxygen species and account for
      increased levels of lipid peroxidation commonly associated with lithium exposure.
      Moreover, lithium was found to down-regulate genes coding for anti-apoptotic gene
      BAG-1 and for most of the molecular chaperones (HSP, GRP). This might account for
      lithium toxicity since these proteins are critical for cell survival. At
      translational level, a 105 kDa protein was found to be over-expressed. This
      protein was recognized by the anti-GRP94, anti-KDEL and anti-phosphoserine
      monoclonal antibodies suggesting that, lithium could induce post-translational
      modifications of GRP94 phosphorylation. Using tunicamycin and thapsigargin, it
      was concluded that lithium effects are not related to defect in N-linked
      glycosylation and/or to changes in calcium homeostasis.

PMID- 17512990
TI  - Plant SET domain-containing proteins: structure, function and regulation.
AB  - Modification of the histone proteins that form the core around which chromosomal
      DNA is looped has profound epigenetic effects on the accessibility of the
      associated DNA for transcription, replication and repair. The SET domain is now
      recognized as generally having methyltransferase activity targeted to specific
      lysine residues of histone H3 or H4. There is considerable sequence conservation
      within the SET domain and within its flanking regions. Previous reviews have
      shown that SET proteins from Arabidopsis and maize fall into five classes
      according to their sequence and domain architectures. These classes generally
      reflect specificity for a particular substrate. SET proteins from rice were found
      to fall into similar groupings, strengthening the merit of the approach taken.
      Two additional classes, VI and VII, were established that include proteins with
      truncated/interrupted SET domains. Diverse mechanisms are involved in shaping the
      function and regulation of SET proteins. These include protein-protein
      interactions through both intra- and inter-molecular associations that are
      important in plant developmental processes, such as flowering time control and
      embryogenesis. Alternative splicing that can result in the generation of two to
      several different transcript isoforms is now known to be widespread. An exciting
      and tantalizing question is whether, or how, this alternative splicing affects
      gene function. For example, it is conceivable that one isoform may debilitate
      methyltransferase function whereas the other may enhance it, providing an
      opportunity for differential regulation. The review concludes with the
      speculation that modulation of SET protein function is mediated by antisense or
      sense-antisense RNA.

PMID- 17512993
TI  - Improved single-copy integration vectors for Staphylococcus aureus.
AB  - We have previously reported the construction of Staphylococcus aureus single-copy
      integration vectors based on the lysogenic bacteriophage L54a site-specific
      recombination system. These vectors can replicate autonomously in Escherichia
      coli, which allows DNA manipulations. In S. aureus, the vectors, which do not
      possess staphylococcal replication function, can only be maintained by
      integrating into the chromosome. However, the original vectors have limited
      cloning sites and do not have protection from potential transcription of external
      promoters. Here we report the improved version of these vectors that circumvent
      these shortcomings. In addition, a second integration site based on the
      bacteriophage phi11 site-specific recombination system has been added such that
      the vectors can integrate either at the L54a attachment site or at the phi11
      attachment site.

PMID- 17512994
TI  - An in vitro model to assess pneumococcal adherence to nasopharyngeal cells under
      competition conditions.
AB  - Pneumococcal conjugate vaccine (PCV7) reduces invasive disease and carriage
      caused by vaccine serotypes (VS). An increase in carriage and disease with non
      vaccine serotypes (NVS) has been observed. We have developed an in vitro model
      with human nasopharyngeal (NP) epithelial cells (Detroit 562) to assess the
      adherence capacity of Streptococcus pneumoniae to NP cells in the presence or
      absence of a competing Pnc strain. Two hundred and fifty pneumococcal (Pnc)
      strains (10 strains per serotype for 7 VS and 18 NVS) were tested for their
      opacity phenotype. Strains exhibiting (> or =50%) the transparent phenotype
      (n=72) were evaluated for their adherence capacity to Detroit 562 cells. Mean
      adherence capacity (> or =129 CFU/well) to NP cells was high for VS 18C, 4, and
      9V and for NVS 16F, 10A, and 6A. In the in vitro competition experiments, VS
      strains out-competed (42/108) or co-existed (43/108) with NVS strains for
      adherence to NP cells in most co-inoculations. By contrast, NVS (15C, 16F, 31,
      and 35B) out-competed with VS in only 9 of 108 co-inoculations. Serotype 16F out
      competed or co-existed with some VS and NVS strains. This model may be used to
      identify Pnc strains of a given serotype with competitive potentials for
      replacement of VS in the nasopharynx and to screen Pnc strains for animal
      colonization models.

PMID- 17512996
TI  - Interplay between familiarity and orientation in face processing: an ERP study.
AB  - In order to tap the electrophysiological correlates of the perceptual and
      structural encoding stages of face processing, we investigated how inversion and
      familiarity affect the face-specific event-related potentials (ERPs) components.
      ERPs were recorded while participants performed a familiarity judgment task with
      upright and inverted photographs of famous and unknown faces. The early P100
      component was found to be sensitive to facial configuration that is disrupted by
      face inversion. Noteworthy, in addition to the ongoing effect of orientation, an
      effect of familiarity, although limited to upright faces, emerged at the
      processing stage indexed by N170. Later on, as witnessed by the P250 component,
      the familiarity effect was generalized to both upright and inverted faces with a
      larger amplitude for inverted famous faces. All in all, the present results
      suggest that the face structural encoding stage is cognitively permeable by
      higher-order factors such as familiarity, especially when familiarity is crucial
      for mastering the task. From a more general viewpoint, these results indicate
      that face processing is subserved by multiple mechanisms in which structural
      (i.e. orientation) and semantic (i.e. familiarity) factors begin to interact at
      early processing stages with different time courses. The electrophysiological
      correlates of these mechanisms are documented by the differential involvement of
      the major ERP components in the "familiarity check". With upright faces
      familiarity affects the N170 component, while with inverted faces it affects
      later components, in keeping with a prolonged time course of the familiarity
      decision when orientation is not upright.

PMID- 17512995
TI  - A real-time PCR for the detection of Salmonella Enteritidis in poultry meat and
      consumption eggs.
AB  - A robust duplex 5' nuclease (TaqMan) real-time PCR was developed and in-house
      validated for the specific detection of Salmonella enterica subspecies enterica
      serovar Enteritidis in whole chicken carcass rinses and consumption eggs. The
      assay uses specifically designed primers and a TaqMan probe to target the Prot6e
      gene located on the S. Enteritidis specific 60-kb virulence plasmid. As an
      internal amplification control to monitor Salmonella DNA in the sample, a second
      primer/TaqMan probe set detects simultaneously the Salmonella specific invA gene.
      The assay identified correctly 95% of the 79 Salmonella Enteritidis strains
      tested comprising 19 different phage types. None of the 119 non-Enteritidis
      strains comprising 54 serovars was positive for the Prot6e gene. The assay
      detection probability was for 10(2) or more genome equivalents 100% and for 10
      equivalents 83%. A pre-PCR sample preparation protocol including a pre-enrichment
      step in buffered peptone water, followed by DNA extraction was applied on low
      levels of artificially contaminated whole chicken carcass rinses and eggs from
      hens as well as 25 potentially naturally contaminated chickens. The detection
      limit was less than three CFU per 50 ml carcass rinse or 10 ml egg. The
      sensitivity and specificity compared to the traditional culture-based detection
      method and serotyping were both 100%. Twenty-five potentially naturally
      contaminated chickens were compared by the real-time PCR and the traditional
      cultural isolation method resulting in four Salmonella positive samples of which
      two were positive for the Prot6e gene and serotyped as S. Enteritidis. We show
      also that Salmonella isolates which have a rough lipopolysaccharide structure
      could be assigned to the serovar Enteritidis by the real-time PCR. This
      methodology can contribute to meet the need of fast identification and detection
      methods for use in monitoring and control measures programmes.

PMID- 17512997
TI  - Influence of treatment time and pulse frequency on Salmonella Enteritidis,
      Escherichia coli and Listeria monocytogenes populations inoculated in melon and
      watermelon juices treated by pulsed electric fields.
AB  - Consumption of unpasteurized melon and watermelon juices has caused several
      disease outbreaks by pathogenic microorganisms worldwide. Pulsed electric field
      (PEF) has been recognized as a technology that may inactivate those bacteria
      present in fluid food products at low temperatures. Hence, PEF treatment at 35
      kV/cm, 4 mus pulse duration in bipolar mode and square shape were applied on
      Salmonella Enteritidis, E. coli and L. monocytogenes populations inoculated in
      melon and watermelon juices without exceeding 40 degrees C outlet temperatures.
      Different levels of treatment time and pulse frequency were applied to evaluate
      their effects on these microorganisms. Treatment time was more influential than
      pulse frequency (P</=0.05) on the PEF microbial reduction levels for both melon
      and watermelon juices. Populations of S. Enteritidis, E. coli and L.
      monocytogenes were experimentally reduced and validated in a single process up to
      3.71+/-0.17, 3.7+/-0.3 and 3.56+/-0.26 log(10) units, respectively, in melon
      juice when 1440 micros and 217 Hz were used; whereas reductions up to 3.56+/
      0.12, 3.6+/-0.4 and 3.41+/-0.13 log(10) units of those microorganisms,
      respectively, were reached in watermelon juice treated for 1727 micros at 188 Hz.
      Although PEF treatment reduced the populations of the three microorganisms, L.
      monocytogenes was more resistant to PEF than S. Enteritidis and E. coli in both
      juices when treated at the same processing conditions.

PMID- 17512999
TI  - Cytoskeletal-antigen specific immunoliposome-targeted in vivo preservation of
      myocardial viability.
AB  - Preservation of cell viability using Cytoskeletal-antigen Specific
      ImmunoLiposomes (antimyosin-CSIL) has been demonstrated in cell cultures. The
      current study utilized the same CSIL intervention for myocardial protection in an
      in vivo rabbit model of acute myocardial infarction. Rabbit hearts with
      experimental left ventricular myocardial infarction were treated with CSIL;
      control liposomes, [(CL), IgG-liposomes (IgG-L) or plain liposomes (PL)], or
      vehicle (placebo). Mean myocardial infarct size in rabbit hearts treated in vivo
      with CSIL was 5 times smaller than in those treated with non-specific CL or
      vehicle. Treatment of ischemic adult myocardium with CSIL results in significant
      preservation of myocardial viability by dramatically decreasing the infarct size
      relative to CL or placebo treatment. Immunohistochemical myocardial preservation
      of CSIL-treated hearts was confirmed by the lack of contraction band necrosis
      using histological H&E stains relative to controls. Electrocardiographic
      confirmation of reduction in myocardial injury after CSIL therapy relative to
      controls was also observed. Application of CSIL technology to non-cardiac tissues
      would confirm a broader applicability of this cell membrane lesion sealing
      technology.

PMID- 17512998
TI  - Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in
      vivo.
AB  - Virus-based nanoparticles (VNPs) from a variety of sources are being developed
      for biomedical and nanotechnology applications that include tissue targeting and
      drug delivery. However, the fate of most of those particles in vivo has not been
      investigated. Cowpea mosaic virus (CPMV), a plant comovirus, has been found to be
      amenable to the attachment of a variety of molecules to its coat protein, as well
      as to modification of the coat protein sequence by genetic means. We report here
      the results of studies of the bio-distribution, toxicology, and pathology of CPMV
      in mice. Plasma clearance and tissue biodistribution were measured using CPMV
      particles derivatized with lanthanide metal complexes. CPMV particles were
      cleared rapidly from plasma, falling to undetectable levels within 20 min. By 30
      min the majority of the injected VNPs were trapped in the liver and to a lesser
      extent the spleen with undetectable amounts in other tissues. At doses of 1 mg,
      10 mg and 100 mg per kg body weight, no toxicity was noted and the mice appeared
      to be normal. Hematology was essentially normal, although with the highest dose
      examined, the mice were somewhat leukopenic with relative decreases in both
      neutrophils and lymphocytes. Histological examination of the spleen showed
      cellular infiltration, which upon flow cytometry analyses revealed elevated B
      lymphocytes on the first day following virus administration that subsequently
      subsided. Microscopic evaluation of various other tissues revealed a lack of
      apparent tissue degeneration or necrosis. Overall, CPMV appears to be a safe and
      non-toxic platform for in vivo biomedical applications.

PMID- 17513002
TI  - Qualitative evaluation of the expectations of low back pain patients with regard
      to information gained through semi-directed navigation on the Internet.
AB  - OBJECTIVES: To make a qualitative analysis of the expectations of chronic low
      back pain (LBP) sufferers with regard to information gained using semi-directed
      Internet navigation on a sample of French LBP-related websites, and to compare
      the results with those of physical medicine and rehabilitation (PMR) medical
      doctors (MD). MATERIAL AND METHODS: Twenty-seven hospitalised chronic LBP
      sufferers assessed in ecological conditions a sample of seven LBP-related
      websites. The sites were assessed using a simplified version of a rating scale of
      patients' expectations. Analysis of the relative importance of the different
      kinds of information delivered was done using a point sharing method. RESULTS: In
      a comfortable environment, patients gave high scores for medical and extra
      medical information, but low scores for website design. Overall quality
      assessment was similar for patients and MDs. The relative importance of medical
      and extra-medical information, and design quality, was similar for Chronic LBP
      patients and MDs. CONCLUSION: PMR MD seemed able to correctly evaluate the
      overall expectations of chronic LBP patients with regard to information, but
      their opinions on the different qualities of websites were different. Doctors and
      patients should collaborate in order to create or validate high quality websites
      concerned with LBP.

PMID- 17513003
TI  - Matrices and scaffolds for drug delivery in vascular tissue engineering.
AB  - The purpose of this review is to give an overview of strategies using natural and
      artificial substrates to present active biomolecules in the development of
      vascular structures. Two primary topics are discussed. The first is the
      replacement and augmentation of arteries using vascular grafts or stents. Second
      is the recruitment of microvasculature secondary to an ischemic event or for the
      purpose of developing perfused, large-volume tissue-engineered constructs.
      Significant overlap exists among these topics. The focus is therefore on specific
      drug delivery strategies with discussion of a number of emerging themes. Where
      applicable, results from clinical trials have been included. Early work in the
      field includes covalent and nonspecific immobilization of growth factors, while
      more recent work emphasizes biologically inspired control over localization and
      temporal presentation. Novel strategies for matrix-mediated release can deliver
      multiple growth factors and/or cells in a manner that mimics tissue development
      and healing. Challenges that remain within this field center on controlling
      reciprocal interactions among the three fundamental tissue engineering components
      of scaffolds, cells and signals.

PMID- 17513004
TI  - Elevated circulating level of osteopontin is associated with advanced disease
      state of non-small cell lung cancer.
AB  - Osteopontin (OPN) plays important roles in tumor progression and metastasis
      through binding to OPN receptors such as alpha(v)beta(beta) integrin and CD44,
      and its overexpression in tumor is associated poor clinical outcome of NSCLC
      patients. Circulating OPN levels, measured by ELISA in 130 NSCLC cases that had
      not been treated for cancer at the time of sampling, were analyzed according to
      clinical, pathologic parameters and single nucleotide polymorphisms (SNPs) in the
      OPN gene promoter. Advanced disease states had higher circulating levels of OPN
      (T4 versus T1-3, N3 versus N0-2, and M1 versus M0, P=.029, .001, and .001,
      respectively, Kruskal-Wallis H-test), reflected by higher level of OPN in stage
      IV than stage I-III (P=.029, Kruskal-Wallis H-test). Among the clinical and
      pathological parameters including age, gender, smoking status, histologic
      subtypes and grade of differentiation, smoking status influences circulating OPN
      level showing higher level of OPN in ex-smokers than current and non-smokers
      (P=.038, Kruskal-Wallis H-test). Variation at nucleotide (nt) -443 of the OPN
      gene promoter had no influence on circulating OPN levels, however, patients with
      G/G at nt -156 showed higher concentrations of OPN than those with G/GG or GG/GG
      (P=.003, Kruskal-Wallis H-test). A patient with G/G at nt -156 was more
      frequently diagnosed with advanced stage (IIIB-IV) than with early stage (I-IIIA)
      NSCLC (P=.048, Mantel-Haenszel-test). In multivariate analysis, stage is the only
      independent factor influencing circulating level of OPN. Although circulating
      level of OPN in the patients with bone metastasis was higher than in those
      without bone metastasis (P=.028, Mann-Whitney U-test), there was no difference in
      the OPN levels between bone metastasis group and non-bone metastasis group. Given
      that the elevated levels of OPN is associated with advanced stages of NSCLC,
      elucidating OPN regulatory mechanisms may contribute to the development of a new
      therapeutic modality for NSCLC.

PMID- 17513005
TI  - Low prevalence of SV40 in Swiss mesothelioma patients after elimination of false
      positive PCR results.
AB  - The association of simian virus 40 (SV40) with malignant pleural mesothelioma is
      currently under debate. In some malignancies of viral aetiology, viral DNA can be
      detected in the patients' serum or plasma. To characterize the prevalence of SV40
      in Swiss mesothelioma patients, we optimized a real-time PCR for quantitative
      detection of SV40 DNA in plasma, and used a monoclonal antibody for
      immunohistochemical detection of SV40 in mesothelioma tissue microarrays. Real
      time PCR was linear over five orders of magnitude, and sensitive to a single gene
      copy. Repeat PCR determinations showed excellent reproducibility. However, SV40
      status varied for independent DNA isolates of single samples. We noted that SV40
      detection rates by PCR were drastically reduced by the implementation of strict
      room compartmentalization and decontamination procedures. Therefore, we
      systematically addressed common sources of contamination and found no cross
      reactivity with DNA of other polyomaviruses. Contamination during PCR was rare
      and plasmid contamination was infrequent. SV40 DNA was reproducibly detected in
      only 4 of 78 (5.1%) plasma samples. SV40 DNA levels were low and not consistently
      observed in paired plasma and tumour samples from the same patient.
      Immunohistochemical analysis revealed a weak but reproducible SV40 staining in 16
      of 341 (4.7%) mesotheliomas. Our data support the occurrence of non-reproducible
      SV40 PCR amplifications and underscore the importance of proper sample handling
      and analysis. SV40 DNA and protein were found at low prevalence (5%) in plasma
      and tumour tissue, respectively. This suggests that SV40 does not appear to play
      a major role in the development of mesothelioma.

PMID- 17513006
TI  - Newly qualified doctors' knowledge about MRSA: uncertainty regarding management
      in the community.

PMID- 17513007
TI  - Predictive factors of meticillin resistance among patients with Staphylococcus
      aureus bloodstream infections at hospital admission.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) is prevalent throughout the
      healthcare system in Spain, particularly in long-term care facilities (LTCF) and
      the incidence of MRSA bloodstream infection (MRSA-BSI) at hospital admission is
      increasing. This study aimed to determine factors that predict meticillin
      resistance among patients who require hospitalization for S. aureus BSI. We
      performed a case-control study comparing patients with S. aureus at hospital
      admission from January 1991 to December 2003. Case patients with MRSA-BSI at
      hospital admission (N=50) were compared with control patients with meticillin
      susceptible S. aureus bloodstream infection (MSSA-BSI) at hospital admission
      (N=98). The incidence of MRSA-BSI at hospital admission increased significantly
      from 0.08 cases/1000 hospital admissions in 1991 to 0.37 cases in 2003 (P<0.001).
      Univariate analysis comparing patients with MRSA- and MSSA-BSI found a
      significant association between meticillin resistance and age >60 years, female
      sex, prior MRSA isolation and healthcare-related BSI. No differences were found
      in underlying conditions such as diabetes, haemodialysis, immunosuppression,
      source of infection or mortality between the two groups. Multivariate analyses
      identified prior MRSA isolation [odds ratio (OR): 41; 95% confidence interval
      (CI): 4-350] and admission from long-term care facilities (OR: 37; 95% CI: 4.5
      316) as independent risk factors for MRSA-BSI.

PMID- 17513008
TI  - Changing prophylactic antibiotic use for Thompson's hemiarthroplasty may reduce
      infection rates.

PMID- 17513009
TI  - Improved endoscope drying standards are needed to prevent true and pseudo
      outbreaks of infection.

PMID- 17513010
TI  - Prevalence and predictors of surgical site infection in Tbilisi, Republic of
      Georgia.
AB  - Surgical site infections (SSIs) are a serious problem worldwide. Little is known
      about the epidemiology of SSI in the former Soviet Union. In order to determine
      the prevalence and predictors of SSI in the Republic of Georgia, we undertook a
      multicentre observational study of SSIs in three urban hospitals in the capital,
      Tbilisi. Point prevalence studies (PPS) were performed every 3-5 weeks from
      September 2000 to January 2002 using the National Nosocomial Infections
      Surveillance (NNIS) System definitions. All patients who had undergone surgery
      and were present in participating departments at study hospitals on the day of
      PPS were included. Of 872 surgical procedures, 146 (16.7%) were complicated by
      SSI. The prevalence of SSI varied by procedure and risk category. On multivariate
      regression analysis, age, wound class, one hospital (B) and urological surgery
      were predictive of SSI. In a separate model, NNIS risk index was highly
      predictive of SSI. Antibiotic prophylaxis was rare (29.5% of operations), while
      postoperative antibiotic use was common. SSI is an important problem in the
      Republic of Georgia. Potential areas for intervention include antibiotic
      prophylaxis and shaving practices for skin preparation.

PMID- 17513011
TI  - Comparison of the antibacterial efficacy and acceptability of an alcohol-based
      hand rinse with two alcohol-based hand gels during routine patient care.
AB  - The aims of this study were to compare the antibacterial efficacy of handrubbing
      with an alcoholic rinse (AHRR) and two different alcoholic gels (AHRG) in
      reducing hand contamination under practical use conditions. We wanted to assess
      the acceptability of the three products and to determine the effect of each
      product on overall hand hygiene compliance. A prospective alternating time-series
      clinical trial was performed in a medical intensive care unit. The study was
      divided into three six-week periods (P1, P2, P3). Handrubbing was achieved with
      Sterillium rinse (AHRR) during P1, sterillium gel(AHRG-1) during P2 and Manugel
      Plus (AHRG-2) during P3. Pre- and post-rubbing hand contaminations were assessed
      immediately after a direct contact with a patient, using the glove juice
      technique. Health care workers (HCWs) evaluated the acceptability of the products
      through a self-administered anonymous questionnaire. Compliance of HCWs with hand
      hygiene was assessed during the three periods. We studied 242 handrubbing
      opportunities. The mean reduction factor (expressed as the Log(10) CFU/mL) of the
      AHRR, AHRG-1 and AHRG-2 were 1.28+/-0.95, 1.29+/-0.84 and 0.51+/-0.73,
      respectively (p<0.001). Assessment of the three products by HCWs indicated that
      AHRR and AHRG-1 were significantly better accepted than AHRG-2. The overall
      compliance of HCWs to hand hygiene was better when gel was available. Under
      practical use conditions, AHRG-1 and AHRR were more effective than AHRG-2,
      although all were claimed to pass the European standard EN1500. In vivo trials
      are essential to compare the antimicrobial efficacy of products for handrubbing.

PMID- 17513012
TI  - Fetal functional capabilities in response to maternal hypertonicity associated
      with altered central and peripheral angiotensinogen mRNA in rats.
AB  - Although a number of studies have shown neural, hormonal, and behavioral
      capabilities in the control of body fluid regulation under conditions of
      dehydration in adults, limited information is available on the development of
      fetal functional abilities in response to osmotic challenge in rats. This study
      was performed to investigate the influence of maternal hypertonicity on fetal
      osmoregulatory capabilities at late gestational time in rats. Maternal and fetal
      plasma osmolality and blood sodium levels were determined and compared at
      continuous time points from 0.5 to 9h following maternal injection of hypertonic
      NaCl. Subcutaneous administration of hypertonic saline evoked a rise in plasma
      osmolality and sodium concentrations in maternal rats and fetuses associated with
      an up-regulation in angiotensinogen gene mRNA in the fetal liver and down
      regulation of the same gene in the fetal brain. The increased levels of fetal
      blood osmolality and sodium were less than that in their mothers, and the fetus
      took less time to balance the enhanced osmolality and sodium concentrations. The
      results suggest that there may exist additional mechanisms in utero at near-term
      in protecting fetuses from hypertonic challenge. In addition, molecular results
      in the present study provide new data on fetal angiotensinogen gene expressed
      differently in the liver and brain under the same condition of prenatal salt
      loading, indicating osmotic signals of intracellular dehydration related to an
      acute increase in angiotensinogen mRNA in the fetal liver, and subsequent
      decrease in angiotensinogen mRNA levels in the fetal brain.

PMID- 17513013
TI  - Oxytocin during pregnancy and early postpartum: individual patterns and maternal
      fetal attachment.
AB  - Oxytocin (OT), a nanopeptide hormone, plays a role in the emergence of maternal
      behavior, yet few studies examined OT in humans across pregnancy and the
      postpartum. We followed healthy women at three points: first trimester of
      pregnancy, third trimester, and first postpartum month. Plasma OT levels showed
      high individual stability. A third of the sample showed consistent OT levels,
      whereas others showed increasing or decreasing trends or peak in late pregnancy.
      The increase in OT from early to late pregnancy correlated with higher maternal
      fetal bonding. These data may help set standards for OT levels and underscore
      links with maternal-infant attachment.

PMID- 17513014
TI  - Neuroprotection: a comparative view of vasoactive intestinal peptide and
      pituitary adenylate cyclase-activating polypeptide.
AB  - The neuroprotective properties of vasoactive intestinal peptide (VIP) and
      pituitary adenylate cyclase-activating polypeptide (PACAP) place these peptides
      in a special category of ligands that have implications for our understanding of
      pathological conditions as well as a potential basis for therapeutic
      intervention. It is remarkable that these peptides have a protective impact
      against such a wide variety of clinical relevant toxic substances. This
      protective diversity is consistent with the multiple pathways that are activated
      or inhibited by the action of these peptides. Although knowledge is emerging on
      the neuroprotective mechanisms of VIP and PACAP, it is already evident that these
      two peptides are not identical in their action and each peptide has multiple
      mechanisms that allow for neuroprotective diversity. The multiple intracellular
      signaling pathways and differing extracellular mediators of neuroprotection
      contribute to this diversity of action. In this review, examples of
      neuroprotective actions will be presented that serve to demonstrate the
      remarkable breadth of neuroprotective processes produced by VIP and PACAP.

PMID- 17513015
TI  - Differential protein expression profiles in the hippocampus of human alcoholics.
AB  - Mild to severe cognitive impairments are frequently observed symptoms in chronic
      alcoholics. Decline of cognitive function significantly affects patients'
      recovery process and prognosis. The hippocampal region is sensitive to the
      effects of alcohol and it has been suggested that alcohol-induced hippocampal
      damage and/or changes in neuronal circuitry play an important role in generating
      these symptoms. Although various hypotheses have been proposed, molecular
      mechanisms underlying these alterations in the hippocampus are largely unknown.
      In the present study, we employed a 2DE-based proteomics approach to compare the
      protein expression profiles of the hippocampus in human alcoholic and healthy
      control brains. In the alcoholic hippocampus, 20 protein spots were found to be
      differentially regulated, 2 increased and 18 decreased. Seventeen proteins were
      identified using mass spectroscopy and were subcategorized into three energy
      metabolic proteins, six protein metabolic proteins, four signalling proteins, two
      oxidative stress-related proteins, one vesicle trafficking protein and one
      cytoskeletal protein. Some of these proteins have been previously implicated in
      alcohol-induced brain pathology. Based upon the results, several hypotheses were
      generated to explain the mechanisms underlying possible functional and/or
      structural alterations induced by chronic alcohol use in this brain region.

PMID- 17513016
TI  - Extrasynaptic transmission and the diffusion parameters of the extracellular
      space.
AB  - Extrasynaptic volume transmission, mediated by the diffusion of neuroactive
      substances in the extracellular space (ECS), plays an important role in short-
      and long-distance communication between nerve cells. The ability of a substance
      to reach extrasynaptic high-affinity receptors via diffusion depends on the ECS
      diffusion parameters, ECS volume fraction alpha (alpha=ECS volume/total tissue
      volume) and tortuosity lambda (lambda2=free/apparent diffusion coefficient),
      which reflects the presence of diffusion barriers represented by, e.g., fine
      astrocytic processes or extracellular matrix molecules. These barriers channel
      the migration of molecules in the ECS, so that diffusion may be facilitated in a
      certain direction, i.e. anisotropic. The diffusion parameters alpha and lambda
      differ in various brain regions, and diffusion in the CNS is therefore
      inhomogeneous. Changes in diffusion parameters have been found in many
      physiological and pathological states, such as development and aging, neuronal
      activity, lactation, ischemia, brain injury, degenerative diseases, tumor growth
      and others, in which cell swelling, glial remodeling and extracellular matrix
      changes are key factors influencing diffusion. Changes in ECS volume, tortuosity
      and anisotropy significantly affect the accumulation and diffusion of neuroactive
      substances and thus extrasynaptic transmission, neuron-glia communication,
      mediator "spillover" and synaptic crosstalk as well as, cell migration. The
      various changes occurring during pathological states can be important for
      diagnosis, drug delivery and treatment.

PMID- 17513017
TI  - Calpastatin levels affect calpain activation and calpain proteolytic activity in
      APP transgenic mouse model of Alzheimer's disease.
AB  - The intracellular Ca(2+)-dependent protease calpain and the specific calpain
      endogenous inhibitor calpastatin are widely distributed, with the
      calpastatin/calpain ratio varying among tissues and species. Increased Ca(2+) and
      calpain activation have been implicated in Alzheimer's disease (AD), with scant
      data available on calpastatin/calpain ratio in AD. Information is lacking on
      calpain activation and calpastatin levels in transgenic mice that exhibit AD-like
      pathology. We studied calpain and calpastatin in Tg2576 mice and in their wild
      type littermates (control mice). We found that in control mice calpastatin level
      varies among brain regions; it is significantly higher in the cerebellum than in
      the hippocampus, frontal and temporal cortex, whereas calpain levels are similar
      in all these regions. In the Tg2576 mice, calpain is activated, calpastatin is
      diminished, and calpain-dependent proteolysis is observed in brain regions
      affected in AD and in transgenic mice (especially hippocampus). In contrast, no
      differences are observed between the Tg2576 and the control mice in the
      cerebellum, which does not exhibit AD-like pathology. The results are consistent
      with the notion that a high level of calpastatin in the cerebellum renders the
      calpain in this brain region less liable to be activated; in the other brain
      parts, in which calpastatin is low, calpain is more easily activated in the
      presence of increased Ca(2+), and in turn the activated calpain leads to further
      diminution in calpastatin (a known calpain substrate). The results indicate that
      calpastatin is an important factor in the regulation of calpain-induced protein
      degradation in the brains of the affected mice, and imply a role for calpastatin
      in attenuating AD pathology. Promoting calpastatin expression may be used to
      ameliorate some manifestations of AD.

PMID- 17513018
TI  - Motor and cognitive deficits in the heterozygous leaner mouse, a Cav2.1 voltage
      gated Ca2+ channel mutant.
AB  - The leaner mutation in mice affects the Ca(v)2.1 voltage-gated calcium channel
      alpha(1A)-subunit gene (Cacna1a), causing a reduction in calcium currents
      predominantly in Purkinje cells. This reduction in calcium currents causes severe
      progressive cerebellar ataxia, beginning around postnatal day 10, in homozygous
      leaner mice (tg(la)/tg(la)), while their heterozygous littermates (tg(la)/+)
      present no obvious behavioral deficits. In humans, heterozygous mutations in the
      Cacna1a orthologous gene produce a broad range of neurological manifestations. To
      evaluate the phenotypic status of the tg(la)/+ animals, we assessed motor
      performance and cognition, at different ages, in these mutant mice. We were able
      to observe age-dependent impairment in motor and cognitive tasks; balance and
      motor learning deficits were found in demanding tasks on the rotarod and on the
      hanging wire test, while spatial learning and memory impairment was observed in
      the Morris water maze. Progressive dysfunction in escape reflexes, indicative of
      neurological impairment, was also present in tg(la)/+ animals. Although not
      presenting major motor alterations, tg(la)/+ mice show age-dependent motor and
      cognitive deficits.

PMID- 17513019
TI  - Quantitative structure activity relationship studies on thiourea analogues as
      influenza virus neuraminidase inhibitors.
AB  - Influenza virus is a major global threat that impacts the world in one form or
      another as flu infections. Neuraminidase, one of the targets for these viruses,
      has recently been exploited in the treatment of these infections. Quantitative
      structure activity relationship studies were performed on thiourea analogues
      using spatial, topological, electronic, thermodynamic and E-state indices.
      Genetic algorithm based genetic function approximation method of variable
      selection was used to generate the model. Highly statistically significant model
      was obtained when number of descriptors in the equation was set to 5. The atom
      type log P and shadow indices descriptors showed enormous contributions to
      neuraminidase inhibition. The validation of the model was done by cross
      validation, randomization and external test set prediction. The model gives
      insight on structural requirements for designing more potent analogues against
      influenza virus neuraminidase.

PMID- 17513020
TI  - Structural and biological studies of mononuclear palladium(II) complexes
      containing N-substituted thiosemicarbazones.
AB  - New complexes of Pd(II) with N-substituted thiosemicarbazone (1)-(3) have been
      synthesised and characterised by elemental analyses, IR, electronic, (1)H NMR
      spectroscopies. The electrochemical behaviour of the complexes has been tested by
      using cyclic voltammetry. The crystal structures of the complexes have been
      determined by single crystal X-ray diffraction technique. In all the complexes
      the thiosemicarbazone ligand is coordinated to palladium through ONS mode. The
      complex 1 crystallises in the monoclinic space group P2(1)/c with two molecules
      per unit cell, has the dimensions of a=9.4390(19)A, b=10.645(2)A, c=13.668(3)A,
      alpha=90 degrees , beta=91.43 degrees and gamma=90 degrees . The complex 3
      crystallises in the monoclinic space group P2(1)/c with four molecules per unit
      cell, has the dimensions of a=14.119(3)A, b=11.155(2)A, c=18.503(4)A, alpha=90
      degrees , beta=112.02 degrees and gamma=90 degrees . The new complexes have been
      tested for their antibacterial activity against various pathogenic bacteria. From
      this study, it was found out that the activity of the complex 2 almost reaches
      the effectiveness of the conventional bacteriocide Streptomycin.

PMID- 17513021
TI  - Novel Pd(II) complexes of 1-N-substituted 3-phenyl-2-pyrazoline derivatives and
      evaluation of antiamoebic activity.
AB  - Cyclization of Mannich base with N(4)-substituted thiosemicarbazides by different
      aliphatic, aromatic and cyclic amines afforded a series of new 1-N-substituted
      cyclised pyrazoline analogues of thiosemicarbazones (PYZ-TSC) 1-10. Reaction of
      [Pd(DMSO)(2)Cl(2)] with pyrazoline derivatives led to new palladium(II) complexes
      [Pd(PYZ-TSC)Cl(2)] 1a-10a. The structures of all the compounds were characterized
      by spectroscopic methods. It was concluded that the pyrazoline thiosemicarbazone
      derivatives have two chelating arms, one attached at the 2-position of the
      pyrazole ring (that is, N donor) and other (S donor) linked to the
      thiosemicarbazone branch. The determination of antiamoebic activity of all the
      compounds was done using HM1:IMSS strain of Entamoeba histolytica, among all the
      complexes, 8a showed the most promising IC(50)=0.37 microM vs. IC(50)=1.81 microM
      of metronidazole, the reference drug. MTT assay showed that the compounds are non
      toxic to human kidney epithelial cell line.

PMID- 17513022
TI  - Synthesis and antimicrobial activity of some novel derivatives of benzofuran:
      part 2. The synthesis and antimicrobial activity of some novel 1-(1-benzofuran-2
      yl)-2-mesitylethanone derivatives.
AB  - The reaction of salicylaldehyde with 1-chloro-3-mesitylacetone (2) and potassium
      carbonate was used to prepare 1-(1-benzofuran-2-yl)-2-mesitylethanone (4) for the
      starting reagent purposes. 1-(1-Benzofuran-2-yl)-2-mesitylethanoneoxime (5) was
      synthesized by the reaction of the compound (4) with hydroxylamine. New
      derivative of 1-(1-benzofuran-2-yl)-2-mesitylethanoneoxime (5) as 1-(1-benzofuran
      2-yl)-2-mesitylethanonesemicarbazone (7) was obtained in very high yields. Alkyl
      substituted N-oxime ethers (8a-d) were obtained by the reaction compound 5 and
      various halogen contained compounds. The compounds 9a-d were synthesized by the
      reaction of the compound (5) and four different acyl chlorides. Some of the
      synthesized compounds were tested for antimicrobial activity against
      Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 25922 and Candida albicans
      ATCC 10231. Among the synthesized compounds (E)-1-(1-benzofuran-2-yl)-2
      mesitylethanone-O-benzoyloxime (9b) was found the most active derivative against
      S. aureus ATCC 6538 and E. coli ATCC 25922. The other compounds exhibited
      moderate activity against the other test microorganisms.

PMID- 17513023
TI  - [MRSA bacteremia: recent epidemiological and therapeutical trends].
AB  - PURPOSE: Staphylococcus aureus is the first agent responsible for nosocomial
      bacteremia in France. About 40% of the strains are resistant to methicillin
      (MRSA). The epidemiology of these infections has changed in the last fifteen
      years whereas therapeutics options have slightly progressed. CURRENT KNOWLEDGE
      AND KEY POINTS: Hospital-acquired MRSA bacteremia are more and more frequent
      while community-acquired strains recently appeared. Factors influencing the
      emergence of these infections were identified thanks to numerous clinical
      studies, as well as patients risk factors for developing these infections and
      their complications. At the same time, intermediate sensitive and resistant MRSA
      strains to glycopeptides appeared. Conversely, the best antibiotic strategy is
      still unclear in absence of good clinical studies. The interest of antibiotics
      combinations and of glycopeptides serum-concentrations control is still a matter
      of debate. Finally, the number of new active molecules remains limited.
      PERSPECTIVES: The frequency and severity of MRSA bacteremia are quite worrying in
      our country. The epidemiology of these infections must be known by every
      clinicians in order to prevent them. The therapeutic strategy has to be better
      define and need for new anti-infectious agents is critic.

PMID- 17513024
TI  - Protein breakdown on whole-body and organ level in non-cachectic tumour-bearing
      mice undergoing surgery.
AB  - BACKGROUND & AIMS: Since both cancer and surgery are known to alter protein
      turnover, we investigated how the presence of tumour affects post-operative
      protein breakdown. METHODS: Controls and tumour-bearing non-cachectic mice were
      studied, both with and without laparotomy (n=8 per group). One day after
      laparotomy, stable isotopes of phenylalanine and 3-methylhistidine were used in a
      steady-state protocol to assess total protein breakdown on whole-body level and
      in muscle, intestines, liver and kidney, in addition to whole-body myofibrillar
      protein breakdown and body composition. Proteasomal chymotrypsin-like activity
      was measured to determine activity of the ATP-dependent ubiquitin pathway.
      RESULTS: On whole-body level, the presence of tumour increased total protein
      breakdown from 47+/-6 to 58+/-4 nmol/10 g/min (p<0.05) and myofibrillar protein
      breakdown from 0.70+/-0.04 to 1.22+/-0.14 nmol/10 g/min (p<0.05) without
      affecting protein breakdown in organs, body composition or proteasomal activity.
      Laparotomy increased myofibrillar protein breakdown in controls (from 0.70+/-0.04
      to 0.98+/-0.12 nmol/10 g/min, p<0.05) and tumour-bearing mice (from 1.22+/-0.14
      to 1.54+/-0.22 nmol/10 g/min, p=0.15) to a similar extent. CONCLUSIONS: Whole
      body total protein breakdown, total protein breakdown across organs, body
      composition or proteasomal activity were not affected by laparotomy. Tumour
      bearing mice had increased total and myofibrillar protein breakdown on whole-body
      level even before weight loss was obvious. However, this did not affect the post
      operative response in protein breakdown or body composition.

PMID- 17513025
TI  - Immunogenicity, safety and tolerability of meningococcal C CRM197 conjugate
      vaccine administered 3, 5 and 11 months post-natally to pre- and full-term
      infants.
AB  - A total of 79 pre-term infants with a gestational age > or =32 weeks and 74 full
      term infants were studied in order to evaluate the immunogenicity, safety and
      tolerability of meningococcal C (MenC)-CRM(197) conjugate vaccine administered 3,
      5 and 11 months post-natally. The evoked immune response seemed to be
      substantially similar in the pre- and full-term infants, and there were only
      clinically marginal differences in safety and tolerability between the groups.
      The results support the use of two doses of MenC-CRM(197) vaccine at 3 and 5
      months of age for primary immunisation, with a booster dose being given at about
      1 year. In addition to reducing costs, this scheme seems to assure global
      immunogenicity and potential efficacy that is better than that offered by the
      accelerated scheme of administration with only three doses of vaccine in the
      first months of life, and similar to that observed with a fourth dose used as
      booster after the first year.

PMID- 17513026
TI  - Does the "hybrid multidirectional test method" generate quality data or
      paradoxical data?

PMID- 17513027
TI  - Can mismatch negativity be linked to synaptic processes? A glutamatergic approach
      to deviance detection.
AB  - This article aims to provide a theoretical framework to elucidate the
      neurophysiological underpinnings of deviance detection as reflected by mismatch
      negativity. A six-step model of the information processing necessary for deviance
      detection is proposed. In this model, predictive coding of learned regularities
      is realized by means of long-term potentiation with a crucial role for NMDA
      receptors. Mismatch negativity occurs at the last stage of the model, reflecting
      the increase in free energy associated with the switching on of silent synapses
      and the formation of new neural circuits required for adaptation to the
      environmental deviance. The model is discussed with regard to the pathological
      states most studied in relation to mismatch negativity: alcohol intoxication,
      alcohol withdrawal, and schizophrenia.

PMID- 17513028
TI  - Possible anti-oxidant and neuroprotective mechanisms of zolpidem in attenuating
      typical anti-psychotic-induced orofacial dyskinesia: a biochemical and
      neurochemical study.
AB  - Tardive dyskinesia is a serious motor side effect of chronic anti-psychotic
      therapy. The pathophysiology of this disabling and commonly irreversible movement
      disorder continues obscure and may be caused due to GABAergic hypofunction or
      increased oxidative damage and free radical generation. Chronic treatment with
      typical antipsychotics leads to the development of abnormal hyperkinetic
      orofacial movements (vacuous chewing movements, tongue protrusions and facial
      jerking) in rats and is widely accepted as the animal model for tardive
      dyskinesia. Zolpidem, a GABA-mimetic drug is structurally related to melatonin
      and has been reported to possess anti-oxidant and neuroprotective effects both in
      vivo and in vitro. The study was carried out to investigate whether zolpidem can
      be used in the treatment of typical anti-psychotic-induced orofacial dyskinesia.
      Chronic haloperidol (1 mg/kg, i.p. for 21 days) and chlorpromazine (5 mg/kg, i.p.
      for 21 days) treatment significantly induced orofacial hyperkinetic movements and
      zolpidem [N, N, 6-trimethyl-2-p-tolyl-imidazo (1, 2-a) pyridine 3-acetamideL-(+)]
      dose dependently (1, 2, 5 mg/kg i.p. for 21 days) reduced these haloperidol and
      chlorpromazine-induced hyperkinetic orofacial movements. Biochemical analysis
      revealed that haloperidol and chlorpromazine treatment significantly induced
      increase in lipid peroxidation and decrease in the levels of total nitric oxide
      levels, non-protein thiols (NPSH) and of anti-oxidant defense enzymes, superoxide
      dismutase (SOD) and catalase in the striatum of rat brain. Co-administration of
      zolpidem (1, 2, 5 mg/kg i.p. for 21 days) significantly reduced the lipid
      peroxidation and restored the non-protein thiols and total nitric oxide levels
      induced by chronic haloperidol and chlorpromazine treatment. It also
      significantly reversed the haloperidol and chlorpromazine-induced decrease in
      brain SOD and catalase activity. Neurochemical analysis (Neurotransmitter and
      their metabolite level estimation) revealed that haloperidol and chlorpromazine
      significantly decreased the dopamine, norepinephrine and serotonin levels in
      brain homogenates where as it caused a significant increase in the metabolite
      (VMA and HVA) levels in urine, which were significantly reversed by zolpidem at
      higher doses. Result of the present study support the therapeutic use of zolpidem
      in the treatment of typical anti-psychotic-induced orofacial dyskinesia.

PMID- 17513029
TI  - Betaxolol, a selective beta(1)-adrenergic receptor antagonist, diminishes anxiety
      like behavior during early withdrawal from chronic cocaine administration in
      rats.
AB  - BACKGROUND: Anxiety has been indicated as one of the main symptoms of the cocaine
      withdrawal syndrome in human addicts and severe anxiety during withdrawal may
      potentially contribute to relapse. As alterations in noradrenergic transmission
      in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the
      present study sought to determine the effect of cocaine withdrawal on beta
      adrenergic receptor (beta(1) and beta(2)) expression in the amygdala. METHODS:
      Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of
      cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine
      injection, amygdala brain regions were micro-dissected and processed for Western
      blot analysis. Results showed that beta(1)-adrenergic receptor, but not beta(2)
      adrenergic receptor expression was significantly increased in amygdala extracts
      of cocaine-withdrawn animals as compared to controls. This finding motivated
      further studies aimed at determining whether treatment with betaxolol, a highly
      selective beta(1)-adrenergic receptor antagonist, could ameliorate cocaine
      withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p.
      injection) was administered at 24 and then 44 h following the final chronic
      cocaine administration. Anxiety-like behavior was evaluated using the elevated
      plus maze test approximately 2 h following the last betaxolol injection.
      Following behavioral testing, betaxolol effects on beta(1)-adrenergic receptor
      protein expression were examined by Western blotting in amygdala extracts from
      rats undergoing cocaine withdrawal. RESULTS: Animals treated with betaxolol
      during cocaine withdrawal exhibited a significant attenuation of anxiety-like
      behavior characterized by increased time spent in the open arms and increased
      entries into the open arms compared to animals treated with only saline during
      cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like
      effects in control animals treated chronically with saline. Furthermore,
      treatment with betaxolol during early cocaine withdrawal significantly decreased
      beta(1)-adrenergic receptor protein expression in the amygdala to levels
      comparable to those of control animals. CONCLUSIONS: The present findings suggest
      that the anxiolytic-like effect of betaxolol on cocaine-induced anxiety may be
      related to its effect on amygdalar beta(1)-adrenergic receptors that are up
      regulated during early phases of drug withdrawal. These data support the efficacy
      of betaxolol as a potential effective pharmacotherapy in treating cocaine
      withdrawal-induced anxiety during early phases of abstinence.

PMID- 17513030
TI  - Autoradiography reveals selective changes in serotonin binding in neocortex of
      patients with temporal lobe epilepsy.
AB  - The main goal of the present study was to evaluate binding to serotonin in the
      neocortex surrounding the epileptic focus of patients with mesial temporal lobe
      epilepsy (MTLE). Binding to 5-HT, 5-HT(1A), 5-HT(4), 5-HT(7) receptors and
      serotonin transporter (5-HTT) in T1-T2 gyri of 15 patients with MTLE and their
      correlations with clinical data, neuronal count and volume were determined.
      Autopsy material acquired from subjects without epilepsy (n=6) was used as
      control. The neocortex from MTLE patients demonstrated decreased cell count in
      layers III-IV (21%). No significant changes were detected on the neuronal volume.
      Autoradiography experiments showed the following results: reduced 5-HT and 5
      HT(1A) binding in layers I-II (24% and 92%, respectively); enhanced 5-HT(4)
      binding in layers V-VI (32%); no significant changes in 5-HT(7) binding; reduced
      5-HTT binding in all layers (I-II, 90.3%; III-IV, 90.3%, V-VI, 86.9%).
      Significant correlations were found between binding to 5-HT(4) and 5-HT(7)
      receptors and age of seizure onset, duration of epilepsy and duration of
      antiepileptic treatment. The present results support an impaired serotoninergic
      transmission in the neocortex surrounding the epileptic focus of patients with
      MTLE, a situation that could be involved in the initiation and propagation of
      seizure activity.

PMID- 17513031
TI  - Reduced evoked fos expression in activity-related brain regions in animal models
      of behavioral depression.
AB  - A previous study showed that two mouse models of behavioral depression, immune
      system activation and depletion of brain monoamines, are accompanied by marked
      reductions in stimulated neural activity in brain regions involved in motivated
      behavior. The present study tested whether this effect is common to other
      depression models by examining the effects of repeated forced swimming, chronic
      subordination stress or acute intraventricular galanin injection - three
      additional models - on baseline or stimulated c-fos expression in several brain
      regions known to be involved in motor or motivational processes (secondary motor,
      M2, anterior piriform cortex, APIR, posterior cingulate gyrus, CG, nucleus
      accumbens, NAC). Each of the depression models was found to reduce the fos
      response stimulated by exposure to a novel cage or a swim stress in all four of
      these brain areas but not to affect the response of a stress-sensitive region
      (paraventricular hypothalamus, PVH) that was included for control purposes.
      Baseline fos expression in these structures was either unaffected or affected in
      an opposite direction to the stimulated response. Pretreatment with either
      desmethylimipramine (DMI) or tranylcypromine (tranyl) attenuated these changes.
      It is concluded that the pattern of a reduced neural function of CNS
      motor/motivational regions with an increased function of stress areas is common
      to 5 models of behavioral depression in the mouse and is a potential experimental
      analog of the neural activity changes occurring in the clinical condition.

PMID- 17513032
TI  - Neuroleptic malignant syndrome caused by combination of risperidone and lithium
      in a patient with multiple medical comorbidities.

PMID- 17513033
TI  - Comparison of load-bearing capacity of direct resin-bonded fiber-reinforced
      composite FPDs with four framework designs.
AB  - OBJECTIVES: This in vitro study was aimed to compare the fracture resistance of
      directly fabricated inlay-retained fiber-reinforced composite (FRC) fixed partial
      dentures (FPDs) with four types of framework designs. METHODS: Forty-eight
      directly fabricated inlay retained FPDs were made of FRC and particulate resin
      composite (everStick/Tetric flow and Ceram). Extracted human mandibular first
      premolars and first molars were as abutments. The following framework designs
      were tested: in the Group A (control group), the framework was made of two
      prepregs of unidirectional glass FRC; the Group B, two prepregs in pontic portion
      were covered with one layer of multidirectional fiber veil FRC; the Group C, the
      FRC prepregs were covered in pontic portion with four short unidirectional FRC
      pieces along the main prepregs; in Group D, one short unidirectional FRC prepregs
      were placed on the main prepregs in 90 degrees angle to the main framework. After
      thermal cycling, FPDs of each group (n=12) were randomly divided into two
      subgroups (n=6). Fracture test was performed at the universal testing machine
      (1mm/min) where FPDs were loaded from the occlusal direction to the occlusal
      fossa or to the buccal cusp. Failure patterns were observed with
      stereomicroscope. Median and 25%/75% percentile values were calculated and
      nonparametric analysis was performed. RESULTS: Compared with three other
      framework designs, the FPDs in Group D showed the highest resistance when loading
      to the occlusal fossa, with maximum load of 2,353.8N (25%/75%: 2,155.5/2,500.0)
      (p=0.000, 0.000, and 0.005 for compared with Group A, B, and C). The same group
      showed also higher resistance when loaded to the buccal cusp (1,416.3N
      (1,409.2/1,480.8)) if compared to the FPDs of the Group A and Group C (p=0.044,
      0.010). In general the FPDs showed higher resistant to loading at the occlusal
      fossa (p<0.05). CONCLUSIONS: This in vitro study showed that inlay-retained FRC
      FPD constructed with direct technique provided high fracture resistance. The
      framework design that provided support for the veneering composite of the pontic
      contributed to the highest load-bearing capacity even when loaded to the buccal
      cusp.

PMID- 17513034
TI  - Emergence of morphological order in the network formation of Physarum
      polycephalum.
AB  - Emergence in a system appears through the interaction of its components, giving
      rise to higher order or complexity in the system. We tested for the presence of
      emergent properties in a biological system using the simplest biological entity
      of a unicellular organism; the plasmodium of Physarum polycephalum, a giant
      unicellular amoeboid organism that forms a network-like tubular structure
      connecting its food sources. We let two plasmodium networks within a single cell
      interact with each other, and observed how the intracellular interaction affected
      the morphologenesis of the plasmodium networks. We found that the two networks
      developed homologous morphology. We further discuss the presence of autonomous
      and emergent properties in homologous network formation.

PMID- 17513035
TI  - Automated tracking of the mitral valve annulus motion in apical echocardiographic
      images using multidimensional dynamic programming.
AB  - We developed a semiautomatic method for tracking the mitral valve annulus (MVA)
      in echocardiographic images, in particular, tracking the septal and the lateral
      mitral valve hinge points. The algorithm is based on multidimensional dynamic
      programming combined with apodized block matching. The method was tested on
      single-beat apical four chamber image sequences of 20 patients with acute
      myocardial infarction. The automated tracking results were evaluated by comparing
      them with the average manual tracking results of two experts. The mitral valve
      hinge point displacements and the total mitral excursions obtained by the
      automatic technique agreed well with those obtained manually and outperformed two
      commonly used tracking methods (forward tracking and minimum tracking). In
      conclusion, this novel semiautomatic tracking method is clinically valuable and
      capable of tracking the MVA motion within the limits of interobserver
      variability. The technique is robust, even in low frame rate, redigitized VCR
      images of clinical quality.

PMID- 17513037
TI  - Zinc-induced downregulation of Notch signaling is associated with cytoplasmic
      retention of Notch1-IC and RBP-Jk via PI3k-Akt signaling pathway.
AB  - The Notch signaling pathway appears to perform an important function in the
      determination of cell fate and in differentiation, in a wide variety of organisms
      and cell types. In this study, we provide evidence that the inactivation of Notch
      signaling by zinc is achieved via a PI3K-Akt-dependent, cytoplasmic retention of
      Notch1-IC and RBP-Jk. Extracellular zinc has been determined to inhibit
      constitutive active mutants of both Notch1 (DeltaEN1) and Notch1-IC-mediated
      transcription. However, in such cases, neither the cleavage pattern of Notch nor
      the protein stability of Notch1-IC and RBP-Jk was found to have significantly
      changed. With regard to the modulation of Notch signaling, zinc appears to exert
      a significant negative influence on the binding occurring between Notch1 and RBP
      Jk, both in vivo and in vitro. The zinc-induced inhibition of Notch signaling can
      be rescued via pretreatment with wortmannin or LY294002, both of which are
      specific PI3K signaling pathway inhibitors. Furthermore, we ascertained that zinc
      triggers the cytoplasmic retention of Notch1-IC and RBP-Jk, and that cytoplasmic
      retention could be rescued via treatment with wortmannin. Overall, we have
      determined that an important relationship exists between zinc and the Notch1
      signaling pathway, and that this relationship is intimately involved with the
      cytoplasmic retention of Notch and RBP-Jk.

PMID- 17513038
TI  - Influence of ethanol-diesel blended fuels on diesel exhaust emissions and
      mutagenic and genotoxic activities of particulate extracts.
AB  - This study was aimed at evaluating the influence of ethanol addition on diesel
      exhaust emissions and the toxicity of particulate extracts. The experiments were
      conducted on a heavy-duty diesel engine and five fuels were used, namely: E0
      (base diesel fuel), E5 (5%), E10 (10%), E15 (15%) and E20 (20%), respectively.
      The regulated emissions (THC, CO, NOx, PM) and polycyclic aromatic hydrocarbon
      (PAH) emissions were measured, and Ames test and Comet assay, respectively, were
      used to investigate the mutagenicity and genotoxicity of particulate extracts.
      From the point of exhaust emissions, the introduction of ethanol to diesel fuel
      could result in higher brake specific THC (BSTHC) and CO (BSCO) emissions and
      lower smoke emissions, while the effects on the brake specific NOx (BSNOx) and
      particulate matters (BSPM) were not obvious. The PAH emissions showed an
      increasing trend with a growth of ethanol content in the ethanol-diesel blends.
      As to the biotoxicity, E20 always had the highest brake specific revertants (BSR)
      in both TA98 and TA100 with or without metabolizing enzymes (S9), while the
      lowest BSR were found in E5 except that of TA98-S9. DNA damage data showed a
      lower genotoxic potency of E10 and E15 as a whole.

PMID- 17513039
TI  - Equilibrium studies of sorption of lead(II) ions by different pectin compounds.
AB  - The adsorption of Pb(II) ions from aqueous solution by different pectin compounds
      was studied in a batch sorption system. Water-soluble low- and high-esterified
      pectins and insoluble calcium pectate beads were investigated. The lead-binding
      capacity of all pectin compounds was highest within the pH range from 7 to 8. The
      binding capacities and rates of Pb(II) ions by pectin compounds were evaluated.
      The Langmuir, Freundlich and BET sorption models were applied to describe the
      isotherms and isotherm constants. Sorption isothermal data could be well
      interpreted by the Langmuir model. These results obtained through the study
      suggest that pectin compounds are favorable sorbers. The largest amount of Pb(II)
      ions were bound by pectin with the low degree of esterfication. Therefore, pectin
      substances may be considered as perspective for sorption and removal of Pb(II)
      ions from wastewaters.

PMID- 17513040
TI  - Detoxification and/or increase of the biodegradability of aqueous solutions of
      dimethoate by means of solar photocatalysis.
AB  - Different methods have been used to measure changes in biodegradability/toxicity
      of aqueous solutions of the pesticide Laition (a commercial formula of
      methidathion) when it is treated by means of TiO(2) photocatalysis: short time
      biological oxygen demand (BOD(st)) was used to determine the instantaneous
      biodegradability of the sample; BOD(5) was also chosen to determine
      biodegradability, employing in this case the manometric method; the BOD(5)/COD
      ratio was also calculated. Finally, the Zahn-Wellens test was employed to
      evaluate the long-term biodegradation of the effluents. The inhibition of the
      respiration of activated sludge in the presence of toxic pollutants was used to
      test the toxicity of the treated sample. An alternative method based on the
      decrease of BOD(5) of a very biodegradable mixture (glucose+glutamic acid) upon
      addition of the toxic solution was also employed. Similar trends were obtained
      with all methods and allowed us to distinguish between two periods: At the
      beginning of the reaction, there is a decrease in the concentration of dimethoate
      to reach complete abatement of this pesticide; this produces a nearly complete
      detoxification of the solution and a very significant increase of
      biodegradability (BOD(5)/COD ratio reached values close to 0.5 and important
      increase of BOD(5) and BOD(st) were observed). Beyond this point, slow
      mineralization is detected, but further improvement of the biodegradability
      cannot be achieved.

PMID- 17513041
TI  - Removal of Cr(VI) from industrial wastewaters by adsorption Part I: determination
      of optimum conditions.
AB  - Aim of this study is the determination of the Cr(VI) removal efficiency of
      treated pine sawdust and also to find out the thermodynamic and kinetic
      parameters of Cr(VI) removal process in batch systems. Sawdust has been treated
      with 1,5-disodium hydrogen phosphate before the adsorption experiments. The
      effects of initial concentration of Cr(VI) ion, temperature, amount of adsorbent
      and pH of the solution on adsorption have been investigated. Optimum conditions
      for adsorption were determined as T=40 degrees C, sawdust dose=4 g, pH 2, by
      using the results of these experiments and an additional set of experiments was
      performed under these optimum conditions in order to see the change in the
      adsorption efficiency. Removal of chromium ion was found as highly dependent on
      pH and initial Cr(VI) concentration of the solution. In order to find out
      thermodynamic and kinetic parameters equilibrium adsorption models were applied.
      Although experimental data confirm with both Langmuir and Freundlich isotherm
      models, they suit most on Langmuir isotherms. Adsorption rate constant was
      determined from Lagergren equation. Equilibrium constants, adsorption free
      energy, enthalpy and entropy change values were also determined. It was found
      that adsorption process follows first order kinetic and adsorption of Cr(VI) on
      sawdust has the spontaneous nature.

PMID- 17513042
TI  - Hydrazine degradation by ultrasonic irradiation.
AB  - The influence of pH on the degradation of hydrazine with a concentration of
      0.1mmol/L was investigated under the stirring (300rpm) and ultrasonic irradiation
      conditions (200kHz, 200W) in the pH range of 1-9. It was found that the hydrazine
      degradation depended greatly upon pH under the ultrasonic irradiation condition,
      while it did not take place over the whole pH range under the stirring condition.
      Although it has been known that OH radicals and hydrogen peroxide are
      sonochemically formed from water, it was considered that the OH radicals played
      an important role of the hydrazine degradation, but not hydrogen peroxide. The pH
      dependence of the hydrazine degradation was discussed in terms of the
      relationship between the chemical structure and the basic dissociation constants
      of hydrazine.

PMID- 17513043
TI  - Catalytic wet air oxidation of chlorophenols over supported ruthenium catalysts.
AB  - A series of noble metal (Pt, Pd, Ru) loaded zirconia catalysts were evaluated in
      the catalytic wet air oxidation (CWAO) of mono-chlorophenols (2-CP, 3-CP, 4-CP)
      under relatively mild reaction conditions. Among the investigated noble metals,
      Ru appeared to be the best to promote the CWAO of CPs as far as incipient-wetness
      impregnation was used to prepare all the catalysts. The position of the chlorine
      substitution on the aromatic ring was also shown to have a significant effect on
      the CP reactivity in the CWAO over 3wt.% Ru/ZrO(2). 2-CP was relatively easier to
      degradate compared to 3-CP and 4-CP. One reason could be the higher adsorption of
      2-CP on the catalyst surface. Further investigations suggested that 3wt.%
      Ru/ZrO(2) is a very efficient catalyst in the CWAO of 2-CP as far as high 2-CP
      conversion and TOC abatement could still be reached at even lower temperature
      (393K) and lower total pressure (3MPa). Additionally, the conversion of 2-CP was
      demonstrated to increase with the initial pH of the 2-CP solution. The
      dechlorination reaction is promoted at higher pH. In all cases, the adsorption of
      the reactants and the reaction intermediates was shown to play a major role. All
      parameters that would control the molecule speciation in solution or the catalyst
      surface properties would have a key effect.

PMID- 17513044
TI  - Degradation of polycyclic aromatic hydrocarbons (PAHs) in contaminated soils by
      Fenton's reagent: a multivariate evaluation of the importance of soil
      characteristics and PAH properties.
AB  - In this study, we investigated how the chemical degradability of polycyclic
      aromatic hydrocarbons (PAHs) in aged soil samples from various contaminated sites
      is influenced by soil characteristics and by PAH physico-chemical properties. The
      results were evaluated using the multivariate statistical tool, partial least
      squares projections to latent structures (PLS). The PAH-contaminated soil samples
      were characterised (by pH, conductivity, organic matter content, oxide content,
      particle size, specific surface area, and the time elapsed since the
      contamination events, i.e. age), and subjected to relatively mild, slurry-phase
      Fenton's reaction conditions. In general, low molecular weight PAHs were degraded
      to a greater extent than large, highly hydrophobic variants. Anthracene,
      benzo(a)pyrene, and pyrene were more susceptible to degradation than other,
      structurally similar, PAHs; an effect attributed to the known susceptibility of
      these compounds to reactions with hydroxyl radicals. The presence of organic
      matter and the specific surface area of the soil were clearly negatively
      correlated with the degradation of bi- and tri-cyclic PAHs, whereas the amount of
      degraded organic matter correlated positively with the degradation of PAHs with
      five or six fused rings. This was explained by enhanced availability of the
      larger PAHs, which were released from the organic matter as it degraded. Our
      study shows that sorption of PAHs is influenced by a combination of soil
      characteristics and physico-chemical properties of individual PAHs. Multivariate
      statistical tools have great potential for assessing the relative importance of
      these parameters.

PMID- 17513045
TI  - Influence of clinoptilolite rock on chemical speciation of selected heavy metals
      in sewage sludge.
AB  - The chemical speciation of Cd, Cu, Pb, Cr and Ni in Torun municipal sewage sludge
      is investigated with addition of a natural sorbent (clinoptilolite rock). The
      total contents of the heavy metals in the sludge are substantially lower than the
      corresponding limits established by European or Polish legislation excepting
      nickel only. But the metals concentrations excepting lead exceed significantly
      the natural background (average contents in soils and in the Earth's crust) in
      dozens. Application of the sequential chemical extraction indicated that the
      metals in the sewage sludge are bound mainly (over 50%) in the residual fraction.
      The metals form the following order by parts of the mobile form: Ni> Cd>> Cr>
      Cu>> Pb. Addition of the clinoptilolite to the sludge leads to the metals
      contents fall in all four fractions of the sequential procedure. Concentrations
      of mobile forms of cadmium, chromium, copper and nickel decrease by 87, 64, 35
      and 24%, respectively, as a result of addition of 9.09% of the clinoptilolite.
      The total decreases of the metals amount after 9.09% clinoptilolite addition to
      the sludge are around 11, 15, 25, 41 and 51% for copper, nickel, chromium,
      cadmium and lead, respectively.

PMID- 17513046
TI  - Singlet molecular oxygen application for 2-chlorophenol removal.
AB  - A special kind of photocatalysis-a photosensitized oxidation involving singlet
      molecular oxygen ((1)O(2)) was applied to decomposition of 2-chlorophenol (2-CP)
      in water solution. The photoprocess was carried out in a homo- and heterogeneous
      system using rose bengal (RB) as a sensitizer. In the homogeneous solution the
      influence of initial 2-CP concentration and pH on reaction rate was observed.
      Based on the kinetic model, the rate constants of (1)O(2) quenching and reaction
      with 2-CP and the rate constant of excited sensitizer quenching by 2-CP were
      determined. In the heterogeneous system, silane gel was a carrier for the
      immobilized sensitizer. In order to estimate kinetic parameters, an attempt was
      made to describe the process using Langmuir-Hinshelwood (L-H) type mechanism. The
      Langmuir equilibrium constants for oxygen and 2-CP adsorbed on the gel surface
      were also estimated.

PMID- 17513047
TI  - Oxidative decolorization of methylene blue using pelagite.
AB  - Pelagite generally has large surface area and high adsorbing and oxidizing
      reactivity due to highly amorphous nature, and high reducing potential of Mn
      (hydro)oxide phases present in it. In the present study, pelagite, collected from
      the East Pacific Ocean, was tested as a potential oxidant for decolorization of
      methylene blue (MB) in a batch system under air-bubbling and motor-stirring
      conditions. The effects of suspension pH (3.0-10.0), MB concentration (10-100
      mgL(-1)) and loading (0.2-3.0 gL(-1)), and particle size (100-200 mesh) of
      pelagite on kinetics of MB decolorization were assessed. Results show that in
      typical concentration range of dye wastewaters (10-50 mgL(-1)), pelagite can be
      used as a highly efficient material for oxidative degradation of MB. MB
      decolorization was through a surface mechanism, that is, formation of surface
      precursor complex between MB and surface bound Mn(III, IV) center, followed by
      electron transfer within the surface complex. Iron (hydro)oxide phases present in
      the pelagite did not play an important role in MB decolorization. Suspension pH
      exerted double-edged effects on MB decolorization by influencing the formation of
      surface precursor complex, and reducing potential of the system. Kinetic rate of
      MB decolorization is directly proportional to saturation degree of available
      reaction sites by MB adsorption. At the initial and later stages, the kinetics
      for MB decolorization with respect to MB concentration, pelagite loading, and
      particle size could be described separately using two pseudofirst rate equations,
      except at very high pelagite loading (3.0 mgL(-1)). Accumulation of Mn(2+) and
      probably some organic intermediates exerted marked inhibitory effect on MB
      decolorization. Vigorous dynamic condition was favorable for MB decolorization.
      The presence of oxygen could enhance MB decolorization to a limited extent.

PMID- 17513048
TI  - Phenol oxidation by a sequential CWPO-CWAO treatment with a Fe/AC catalyst.
AB  - Catalytic wet peroxide oxidation (CWPO) of phenol with a homemade Fe/activated
      carbon (Fe/AC) catalyst has been studied in a stainless steel fixed-bed reactor
      at different operating conditions (T=23-100 degrees C, P(T)=1-8atm, W=0-2.5g, and
      tau=20-320g(CAT)h/g(Phenol)). The results show that, thanks to the incorporation
      of Fe on the activated carbon, phenol conversion improved dramatically, reaching
      a 90% at 65 degrees C, 2atm, and 40g(CAT)h/g(Phenol). However, TOC conversion
      values remain fairly low, (around 5% at 40g(CAT)h/g(Phenol)), and no improvement
      was obtained with the inclusion of Fe. The presence of Fe seems to promote the
      nondesirable coupling reactions that take place in CWPO of phenol due to the
      condensation of the ring intermediates (the primary phenol oxidation products).
      These condensation products are quite refractory to CWPO at the conditions
      employed. Taking advantage of the high phenol conversions in CWPO and the high
      phenol mineralization in CWAO, along with the good stability of the Fe/AC
      catalyst, a CWPO-CWAO sequential treatment has been successfully performed by
      using a fixed-bed and trickle-bed reactor in series. A CWPO treatment at ambient
      conditions followed by a CWAO treatment at mild conditions (100 degrees C and
      8atm) is presented as high efficiency process for the decontamination of phenolic
      wastewaters.

PMID- 17513049
TI  - Characteristics of titania supported copper oxide catalysts for wet air oxidation
      of phenol.
AB  - Various techniques have been used to characterize the CuO(x)/TiO(2) catalysts
      with different copper loading. Surface area, pore volume and pore size
      distribution of the prepared catalysts were estimated from nitrogen adsorption
      isotherm. Temperature programmed reduction (TPR), X-ray diffraction (XRD),
      electron spin resonance (ESR), X-ray photoelectron spectroscopy (XPS) and X-ray
      absorption near edge structure (XANES) experiments were performed to investigate
      the chemical state of the copper species. The chemical state of copper in the
      CuO(x)/TiO(2) catalysts varied with copper loading (1-25wt.%): highly dispersed
      Cu(2+) cluster for 1 and 5wt.%, and bulk CuO for 7-25wt.%. The activity and
      mineralization selectivity of the CuO(x)/TiO(2) catalysts increased with copper
      loading up to 20wt.%, and remained almost constant for higher copper loading. The
      optimum copper loading was 20wt.% for the wet air oxidation of phenol over the
      CuO(x)/TiO(2) catalysts in this work. The stability of the CuO(x)/TiO(2)
      catalysts with different copper loading was also studied with respect to
      carbonaceous deposits and copper leaching.

PMID- 17513050
TI  - Contribution of glutamate transporter GLT-1 to removal of synaptically released
      glutamate at climbing fiber-Purkinje cell synapses.
AB  - Rapid removal of synaptically released glutamate from the extracellular space
      ensures a high signal-to-noise ratio in excitatory neurotransmission. In the
      cerebellum, glial glutamate transporters, GLAST and GLT-1, are co-localized in
      the processes of Bergmann glia wrapping excitatory synapses on Purkinje cells
      (PCs). Although GLAST is expressed six-fold more abundantly than GLT-1, the decay
      kinetics of climbing fiber-mediated excitatory postsynaptic currents (CF-EPSCs)
      in PCs in GLAST(-/-) mice are not different from those in wild-type (WT) mice.
      This raises a possibility that GLT-1 plays a significant role in clearing
      glutamate at CF-PC synapses despite its smaller amount of expression. Here, we
      studied the functions of GLT-1 and GLAST in the clearance of glutamate using
      GLAST(-/-) mice and GLT-1(-/-) mice. In the presence of cyclothiazide (CTZ) that
      attenuates the desensitization of AMPA receptors, the decay time constant of CF
      EPSCs (tau(w)) in GLT-1(-/-) mice was slower than that in WT mice. However, the
      degree of this prolongation of tau(w) was less prominent compared to that in
      GLAST(-/-) mice. The values of tau(w) in GLT-1(-/-) mice and GLAST(-/-) mice were
      comparable to those estimated in WT mice in the presence of a potent blocker of
      glial glutamate transporters (2S,3S)-3-[3-(4
      methoxybenzoylamino)benzyloxy]aspartate (PMB-TBOA) at 10 and 100 nM, which
      reduced the amplitudes of glutamate transporter currents elicited by CF
      stimulation in Bergmann glia to approximately 81 and approximately 28%,
      respectively. We conclude that GLT-1 plays a minor role compared to GLAST in
      clearing synaptically released glutamate at CF-PC synapses.

PMID- 17513052
TI  - Multidimensional Pain Inventory derived classifications of chronic pain: evidence
      for maladaptive pain-related coping within the dysfunctional group.
AB  - This study examines maladaptive pain-related fear-avoidance and endurance coping
      in subgroups of patients with chronic back pain. Hypotheses were derived from the
      avoidance-endurance model of pain [Hasenbring M. Attentional control of pain and
      the process of chronification. In: Sandkuhler J, Bromm B, Gebhart GF, editors.
      Progress in pain research, vol. 129. New York: Elsevier; 2000. p. 525-34.], which
      assumes that endurance coping (cognitive, behavioral tendency to endure severe
      pain to finish current activities irrespective of pain increases) leads to
      overuse of muscles, joints, and discs with an increase of pain as long-term
      consequence. Participants were 120 patients referred for treatment of chronic
      pain to General Practices. They were classified as 'dysfunctional-DYS' (15.8%),
      'interpersonally distressed-ID' (10.8%), and 'adaptive copers-AC' (61.7%) based
      on the Multidimensional Pain Inventory [Kerns RD, Turk DC, Rudy TE. The West
      Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain 1985;23:345-56.] and
      compared on measures of pain-related fear-avoidance coping (anxiety/depression;
      help-/hopelessness; catastrophizing; avoidance of social/physical activity) and
      endurance coping (positive mood; thought suppression; endurance behavior) using
      the Kiel Pain Inventory [Hasenbring M. The Kiel Pain Inventory-Manual. Three
      questionnaire scales for assessment of pain-related cognitions, emotions and
      copying strategies. Bern:Huber; 1994.]. Multivariate analysis of variance
      indicated that groups differed significantly for pain-related fear-avoidance and
      endurance coping, even after control for pain intensity and depression.
      Univariate effects revealed that patients classified as DYS reported more
      anxiety/depression, help-/hopelessness, and catastrophizing than did those
      classified as AC. Furthermore, the DYS group showed more thought suppression
      compared to AC; however, subgroups did not differ significantly with regard to
      avoidance of social and physical activity, and endurance behavior. Further, DYS
      as well as ID group showed more non-verbal pain behavior compared to AC, which
      refers to the special role of operant conditioning. Implications are considered
      for further investigation of endurance coping to provide a more comprehensive
      assessment and treatment for subgroups of chronic pain patients.

PMID- 17513051
TI  - When administered into the nucleus accumbens core or shell, the NMDA receptor
      antagonist AP-5 reinstates cocaine-seeking behavior in the rat.
AB  - Nucleus accumbens glutamate transmission plays a critical role in cocaine priming
      induced reinstatement of drug seeking. Previous studies have demonstrated that
      systemic or intra-accumbens shell administration of an NMDA receptor antagonist
      reinstates cocaine-seeking behavior. However, it is unclear if antagonizing NMDA
      receptors in the nucleus accumbens core or shell subregions will differentially
      affect cocaine reinstatement. To investigate this possibility, we microinjected
      the competitive NMDA receptor antagonist AP-5 (0, 3 or 30 microg) into either the
      nucleus accumbens core or shell and assessed the reinstatement of cocaine-seeking
      behavior. When microinjected into the shell, both doses of AP-5 produced
      reinstatement of cocaine seeking. In contrast, when administered into the core,
      only the highest dose of AP-5 reinstated cocaine-seeking behavior; moreover, the
      magnitude of this effect was substantially less than when AP-5 was administered
      into the shell. This study provides evidence that pharmacological antagonism of
      NMDA receptors in the nucleus accumbens core or shell promotes the reinstatement
      of cocaine seeking.

PMID- 17513053
TI  - Sequence polymorphism in the ribosomal DNA internal transcribed spacers differs
      among Theileria species.
AB  - The genomic region spanning the two ribosomal RNA internal transcribed spacers
      (ITS1 and ITS2) and the 5.8S rRNA gene was cloned and sequenced from sixteen
      Theileria isolates. Each Theileria species possessed ITS1 and ITS2 of unique
      size(s) and species specific nucleotide sequences. Varying degrees of ITS1 and
      ITS2 intra- and inter-species sequence polymorphism were found among ruminant
      Theileria species. The spacers were most polymorphic in the agent of tropical
      theileriosis, Theileria annulata, and were more conserved in two benign species,
      Theileria buffeli and Theileria sergenti Chitose. Phylogenetic analysis of the
      rDNA ITS1-5.8S rRNA gene-ITS2 region clearly separated each taxon, placing them
      in three clusters. One held T. annulata, Theileria parva, and Theileria mutans,
      with the latter two most closely related. The second held T. sergenti Ikeda, T.
      sergenti Chitose, and T. buffeli, with the latter two most closely related. The
      third cluster held the Theileria ovis isolates.

PMID- 17513054
TI  - Evaluation of Metarhizium anisopliae (Hyphomycetes) for the control of Boophilus
      microplus (Acari: Ixodidae) on naturally infested cattle in the Mexican tropics.
AB  - The efficacy of Metarhizium anisopliae on the control of Boophilus microplus in
      cattle infested naturally in the Mexican tropics was evaluated. The study was
      carried out on a ranch in Veracruz, Mexico. Twenty steers were randomly allocated
      into two groups of 10 cattle. Animals were naturally infested with B. microplus.
      Animals in the treated group were sprayed with M. anisopliae (strain Ma34) at a
      concentration of 1x10(8)conidia/ml every 15 days (four treatments). The other
      group remained as untreated control. Standard engorged female ticks were recorded
      on days 0, 1, 3, 5, 7 and 14 post-treatment. From the second application
      treatment (day 7) to the end of the experiment, animals in the treated group had
      lower tick infestation (P<0.05) with an efficacy of 40.0-91.2%. The results
      demonstrate the efficacy of repeated treatment with M. anisopiae (Ma34 strain) to
      control natural infestation of engorged female B. microplus on cattle in the
      Mexican tropics.

PMID- 17513055
TI  - Mass chemical burn casualty: emergency management of 118 patients with alkali
      burn during a Matsa typhoon attack in Shanghai, China in 2005.
AB  - BACKGROUND: This article reports a chemical burn incident that occurred on August
      7th, 2005, when a Matsa typhoon hit Shanghai, China. This is the largest chemical
      burn incident reported in the literature for 20 years in China, involving 118
      alkali burn patients who were rescued by the Burn Department of Shanghai Changhai
      Hospital independently. METHODS: The scene of the incident was investigated, and
      the clinical, emergency and hospitalized data of the patients were summarized.
      RESULTS: The main injurious chemical was a water solution of sodium hydroxide and
      ammonium chloride. The 118 victims were mostly young men with 5%TBSA deep
      thickness burn of both lower extremities, including 31 patients who had
      additional light coughing. Of 58 patients who were finally hospitalized, 42
      patients received surgical treatment. Most of these patients recovered within 1
      month. There were no deaths. DISCUSSION: Retrospective analysis of the
      therapeutic data of the incident demonstrates that pre-designed disaster planning
      for emergency management of mass burn patients, an effective command group,
      accurate assessment of pathological conditions, and correct allocation of
      different casualties are key elements in successful management in a mass casualty
      even involving burn patients. In addition, it is essential for specialized
      personnel to take part in emergency treatment of chemical burns.

PMID- 17513056
TI  - Mobile phone explosion burn.

PMID- 17513057
TI  - Timing of chest radiotherapy in patients with limited stage small cell lung
      cancer: a systematic review and meta-analysis of randomised controlled trials.
AB  - BACKGROUND: We undertook a systematic review and literature-based meta-analysis
      to determine whether the timing of chest radiotherapy may influence the survival
      of patients with limited stage small cell lung cancer (LS-SCLC). OBJECTIVES: To
      establish the most effective way of combining chest radiotherapy with
      chemotherapy for patients with limited-stage small cell lung cancer in order to
      improve long-term survival. MATERIALS: Eligible studies were identified according
      to the Cochrane Collaboration Guidelines and were randomised controlled clinical
      trials comparing different timing of chest radiotherapy in patients with LS-SCLC.
      Early chest irradiation was defined as beginning within 30 days after the start
      of chemotherapy. RESULTS: Seven randomised trials were eligible. The overall
      survival at 2 years or at 5 years was not significantly different between early
      or late chest radiotherapy. When only trials were considered that used platinum
      chemotherapy concurrent with chest radiotherapy, significantly higher 2 and 5
      year survival rates were observed when chest radiotherapy (RT) was started within
      30 days after the start of chemotherapy (2-year survival: HR: 0.73, 95% CI 0.57
      0.94, p=0.01; 5-year survival: HR: 0.65, 95% CI 0.45-0.93, p=0.02). This was even
      more pronounced when the overall treatment time of chest radiotherapy was less
      than 30 days. In studies that did not show a survival advantage by early chest
      radiation, a lower dose-intensity of chemotherapy in the early vs. late arm was
      observed. CONCLUSIONS: When platinum-based chemotherapy concurrently with chest
      RT is used, the 2- and 5-year survival rates of patients with LS-SCLC may be in
      favour of early chest radiotherapy, with a significant difference if the overall
      treatment time of chest radiation is less than 30 days.

PMID- 17513058
TI  - May genetic factors play a role in the risk of antidepressant-induced suicide?

PMID- 17513059
TI  - Intrafraction motion of the prostate during external-beam radiation therapy:
      analysis of 427 patients with implanted fiducial markers.
AB  - PURPOSE: To analyze the intrafraction motion of the prostate during external-beam
      radiation therapy of patients with prostate cancer. METHODS AND MATERIALS:
      Between August 2001-December 2005, 427 patients with Stage T3Nx/0Mx/0 prostate
      carcinoma received intensity-modulated radiation therapy treatment combined with
      position verification with fiducial gold markers. For a total of 11,426 treatment
      fractions (average, 27 per patient), portal images were taken of the first
      segment of all five beams. The irradiation time of the technique varied between 5
      7 min. From these data, the location of gold markers could be established within
      every treatment beam under the assumption of minimal marker movement. RESULTS: In
      66% of treatment fractions, a motion outside a range of 2 mm was observed, with
      28% outside a range of 3 mm. The intrafraction marker movements showed that
      motion directions were often reversed. However, the effect was small. Even with
      perfect online position-correction at the start of irradiation, intrafraction
      motion caused position uncertainty, but systematic errors (Sigma) were limited to
      <0.6 mm, and random errors (sigma) to <0.9 mm. This would result in a lower limit
      of 2 mm for margins, in the absence of any other uncertainties. CONCLUSIONS:
      Intrafraction motion of the prostate occurs frequently during external-beam
      irradiation on a time scale of 5-7 min. Margins of 2 mm account for these
      intrafraction motions. However, larger margins are required in practice to
      accommodate other uncertainties in the treatment.

PMID- 17513060
TI  - Positional stability of electromagnetic transponders used for prostate
      localization and continuous, real-time tracking.
AB  - PURPOSE: To determine the relative positional stability of implanted glass
      encapsulated circuits (transponders) used in continuous electromagnetic
      localization and tracking of target volumes during radiation therapy. Ideally,
      the distances between transponders remains constant over the course of treatment.
      In this work, we evaluate the accuracy of these conditions. METHODS AND
      MATERIALS: Three transponders were implanted in each of 20 patients. Images (CT
      scan or X-ray pair) were acquired at 13 time points. These images occurred from
      the day of implant (2 weeks before simulation) to 4 weeks posttreatment. The
      distance between transponders was determined from each dataset. The average and
      standard deviation of each distance were determined, and changes were evaluated
      over several time periods, including pretreatment and during therapy. RESULTS: Of
      60 transponders implanted, 58 showed no significant migration from their intended
      positions. Of the two transponders that did migrate, one appears to have been
      implanted in the venous plexus, and the other in the urethra, with no clinical
      consequences to the patients. An analysis that included the planning CT scan and
      all subsequent distance measurements showed that the standard deviation of
      intertransponder distances was < or =1.2 mm for up to 1 month after the
      completion of therapy. CONCLUSIONS: Implanted transponders demonstrate the same
      long-term stability characteristics as implanted gold markers, within statistical
      uncertainties. As with gold markers, and using the same implant procedure, basic
      guidelines for the placement of transponders within the prostate help ensure
      minimal migration.

PMID- 17513061
TI  - Patterns of recurrence analysis in newly diagnosed glioblastoma multiforme after
      three-dimensional conformal radiation therapy with respect to pre-radiation
      therapy magnetic resonance spectroscopic findings.
AB  - PURPOSE: To determine whether the combined magnetic resonance imaging (MRI) and
      magnetic resonance spectroscopy imaging (MRSI) before radiation therapy (RT) is
      valuable for RT target definition, and to evaluate the feasibility of replacing
      the current definition of uniform margins by custom-shaped margins based on the
      information from MRI and MRSI. METHODS AND MATERIALS: A total of 23 glioblastoma
      multiforme (GBM) patients underwent MRI and MRSI within 4 weeks after surgery but
      before the initiation of RT and at 2-month follow-up intervals thereafter. The
      MRSI data were quantified on the basis of a Choline-to-NAA Index (CNI) as a
      measure of spectroscopic abnormality. A combined anatomic and metabolic region of
      interest (MRI/S) consisting of T2-weighted hyperintensity, contrast enhancement
      (CE), resection cavity, and CNI2 (CNI >or= 2) based on the pre-RT imaging was
      compared to the extent of CNI2 and the RT dose distribution. The spatial
      relationship of the pre-RT MRI/S and the RT dose volume was compared with the
      extent of CE at each follow-up. RESULTS: Nine patients showed new or increased CE
      during follow-up, and 14 patients were either stable or had decreased CE. New or
      increased areas of CE occurred within CNI2 that was covered by 60 Gy in 6
      patients and within the CNI2 that was not entirely covered by 60 Gy in 3
      patients. New or increased CE resided within the pre-RT MRI/S lesion in 89% (8/9)
      of the patients with new or increased CE. CONCLUSION: These data indicate that
      the definition of RT target volumes according to the combined morphologic and
      metabolic abnormality may be sufficient for RT targeting.

PMID- 17513062
TI  - Prostate postbrachytherapy seed distribution: comparison of high-resolution,
      contrast-enhanced, T1- and T2-weighted endorectal magnetic resonance imaging
      versus computed tomography: initial experience.
AB  - PURPOSE: To compare contrast-enhanced, T1-weighted, three-dimensional magnetic
      resonance imaging (CEMR) and T2-weighted magnetic resonance imaging (T2MR) with
      computed tomography (CT) for prostate brachytherapy seed location for dosimetric
      calculations. METHODS AND MATERIALS: Postbrachytherapy prostate MRI was performed
      on a 1.5 Tesla unit with combined surface and endorectal coils in 13 patients.
      Both CEMR and T2MR used a section thickness of 3 mm. Spiral CT used a section
      thickness of 5 mm with a pitch factor of 1.5. All images were obtained in the
      transverse plane. Two readers using CT and MR imaging assessed brachytherapy seed
      distribution independently. The dependency of data read by both readers for a
      specific subject was assessed with a linear mixed effects model. RESULTS: The
      mean percentage (+/- standard deviation) values of the readers for seed detection
      and location are presented. Of 1205 implanted seeds, CEMR, T2MR, and CT detected
      91.5% +/- 4.8%, 78.5% +/- 8.5%, and 96.1% +/- 2.3%, respectively, with 11.8% +/-
      4.5%, 8.5% +/- 3.5%, 1.9% +/- 1.0% extracapsular, respectively. Assignment to
      periprostatic structures was not possible with CT. Periprostatic seed assignments
      for CEMR and T2MR, respectively, were as follows: neurovascular bundle, 3.5% +/-
      1.6% and 2.1% +/- 0.9%; seminal vesicles, 0.9% +/- 1.8% and 0.3% +/- 0.7%;
      periurethral, 7.1% +/- 3.3% and 5.8% +/- 2.9%; penile bulb, 0.6% +/- 0.8% and
      0.3% +/- 0.6%; Denonvillier's Fascia/rectal wall, 0.5% +/- 0.6% and 0%; and
      urinary bladder, 0.1% +/- 0.3% and 0%. Data dependency analysis showed
      statistical significance for the type of imaging but not for reader
      identification. CONCLUSION: Both enumeration and localization of implanted seeds
      are readily accomplished with CEMR. Calculations with MRI dosimetry do not
      require CT data. Dose determinations to specific extracapsular sites can be
      obtained with MRI but not with CT.

PMID- 17513063
TI  - Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a
      treatment planning comparison.
AB  - PURPOSE: To compare intensity-modulated photon radiotherapy (IMRT) with three
      dimensional conformal proton therapy (3D-CPT) for early-stage prostate cancer,
      and explore the potential utility of intensity-modulated proton therapy (IMPT).
      METHODS AND MATERIALS: Ten patients were planned with both 3D-CPT (two parallel
      opposed lateral fields) and IMRT (seven equally spaced coplanar fields).
      Prescribed dose was 79.2 Gy (or cobalt Gray-equivalent, [CGE] for protons) to the
      prostate gland. Dose-volume histograms, dose conformity, and equivalent uniform
      dose (EUD) were compared. Additionally, plans were optimized for 3D-CPT with
      nonstandard beam configuration, and for IMPT assuming delivery with beam
      scanning. RESULTS: At least 98% of the planning target volume received the
      prescription dose. IMRT plans yielded better dose conformity to the target,
      whereas proton plans achieved higher dose homogeneity and better sparing of
      rectum and bladder in the range below 30 Gy/CGE. Bladder volumes receiving more
      than 70 Gy/CGE (V70) were reduced, on average, by 34% with IMRT vs. 3D-CPT,
      whereas rectal V70 were equivalent. EUD from 3D-CPT and IMRT plans were
      indistinguishable within uncertainties for both bladder and rectum. With the use
      of small-angle lateral-oblique fields in 3D-CPT and IMPT, the rectal V70 was
      reduced by up to 35% compared with the standard lateral configuration, whereas
      the bladder V70 increased by less than 10%. CONCLUSIONS: In the range higher than
      60 Gy/CGE, IMRT achieved significantly better sparing of the bladder, whereas
      rectal sparing was similar with 3D-CPT and IMRT. Dose to healthy tissues in the
      range lower than 50% of the target prescription was substantially lower with
      proton therapy.

PMID- 17513064
TI  - Late rectal complications evaluated by computed tomography-based dose
      calculations in patients with cervical carcinoma undergoing high-dose-rate
      brachytherapy.
AB  - PURPOSE: To investigate the efficacy of dose calculations at the computed
      tomography (CT)-based rectal point (CTRP) as a predictive factor for late rectal
      complications in patients with cervical carcinoma who were treated with a
      combination of high-dose-rate intracavitary brachytherapy and external beam
      radiotherapy. METHODS AND MATERIALS: Ninety-two patients with uterine cervical
      carcinoma undergoing definitive radiotherapy alone were retrospectively analyzed.
      The median follow-up time for all patients was 32 months (range, 13-60 months).
      The cumulative biologically effective dose (BED) was calculated at the rectal
      reference point as defined by the International Commission on Radiation Units and
      Measurements Report 38 (BED(RP)) and at the CTRP (BED(CTRP)). Late rectal
      complications were recorded according to the Radiation Therapy Oncology Group
      grading system. RESULTS: The late rectal complications were distributed as
      follows: Grade 0, 68 patients (74%); Grade 1, 20 patients (22%); Grade 2, 4
      patients (4%). Univariate analysis showed that BED(RP), BED(CTRP), RP dose/point
      A dose ratio, and CTRP dose/point A dose ratio were significantly correlated with
      late rectal complications (p < 0.05). On multivariate analysis, patients with a
      rectal BED(CTRP) >/=140 Gy(3) presented with significantly greater frequency of
      rectal complications (p = 0.031). CONCLUSIONS: The present results suggest that
      BED(CTRP) is a useful predictive factor for late rectal complications.

PMID- 17513065
TI  - Nasopharyngeal cancers: which method should be used to measure these irregularly
      shaped tumors on cross-sectional imaging?
AB  - PURPOSE: To determine whether the standard techniques of measuring tumor size and
      change in size after treatment could be applied to the measurement of
      nasopharyngeal cancers, which are often irregular in shape. METHODS AND
      MATERIALS: The standard measurements of bidimensional (BDM) (World Health
      Organization criteria) and unidimensional (UDM) (Response Evaluation Criteria in
      Solid Tumors [RECIST] criteria), together with the maximum depth of the tumor
      perpendicular to the pharyngeal wall (DM), were acquired from axial magnetic
      resonance images of primary nasopharyngeal carcinoma in 44 patients at diagnosis
      and in 29 of these patients after treatment. Tumor volume measurements (VM),
      acquired from the summation of areas from the axial magnetic resonance images,
      were used as the reference standard. RESULTS: There was a significant association
      between VM and BDM with respect to tumor size at diagnosis (p = 0.002), absolute
      change in tumor size after treatment (p < 0.001), and percentage change in tumor
      size after treatment (p = 0.044), but not between VM and UDM. There was also a
      significant association between VM and DM with respect to percentage change in
      tumor size after treatment (p = <0.0001) but not absolute change (p = 0.222).
      CONCLUSION: When using simple measurements to assess irregularly shaped
      nasopharyngeal cancers, the BDM should be used to measure size at diagnosis and
      the BDM and percentage change in size with treatment. Unidimensional measurement
      does not reflect size or change in size, and therefore the RECIST criteria may
      not be applicable to all tumor shapes. The use of DM requires further evaluation.

PMID- 17513066
TI  - Dose as a function of lung volume and planned treatment volume in helical
      tomotherapy intensity-modulated radiation therapy-based stereotactic body
      radiation therapy for small lung tumors.
AB  - PURPOSE: To evaluate the limitations of Hi-Art Helical Tomotherapy (Middleton,
      WI) stereotactic body radiotherapy (SBRT) for lung lesions, and to provide an
      initial report on patients treated with this method. Stereotactic body
      radiotherapy was shown to be an effective, well-tolerated treatment for early
      stage, non-small-cell lung carcinoma (NSCLC). The Radiation Therapy Oncology
      Group (RTOG) 0236 protocol is currently evaluating three-dimensional conformal
      SBRT that delivers 60 Gy in three fractions. METHODS AND MATERIALS: Inverse
      treatment planning for hypothetical lung gross tumor volumes (GTV) and planned
      treatment volume (PTV) expansions were performed. We tested the hypothesis that
      the maximum acceptable dose (MAD) to be delivered to the lesion by SBRT could be
      predicted by PTV and lung volume. Dose constraints on normal tissue were as
      designated by the RTOG protocol. Inverse planning was performed to find the
      maximum tolerated SBRT dose up to 60 Gy. RESULTS: Regression analysis of the data
      obtained indicated a linear relationship between MAD, PTV, and lung volume. This
      generated two equations which may be useful predictive tools. Seven patients with
      Stage I and II NSCLC treated at the University of Virginia with this method
      tolerated the treatment extremely well, and suffered no greater than grade I
      toxicity, with no evidence of disease recurrence in follow-up from 2-20 months.
      CONCLUSIONS: Helical tomotherapy SBRT for lung lesions is well-tolerated. In
      addition, the likely MAD for patients considered for this type of treatment can
      be predicted by PTV and lung volume.

PMID- 17513067
TI  - Angiotensin-converting enzyme inhibition by Brazilian plants.
AB  - The potential antihypertensive activity of Brazilian plants was evaluated in
      vitro by its ability to inhibit the angiotensin-converting enzyme (ACE). Forty
      four plants belonging to 30 families were investigated. Plants were selected
      based on their popular use as antihypertensive and/or diuretics. The following
      plants presented significant ACE inhibition rates: Calophyllum brasiliense,
      Combretum fruticosum, Leea rubra, Phoenix roebelinii and Terminalia catappa.

PMID- 17513068
TI  - [Prosthetic repair of genito-urinary prolapses by the transobturateur
      infracoccygeal hammock technique: medium-term results].
AB  - OBJECTIVES: The aim of this study was to evaluate the anatomical and functional
      medium-term efficacy and possible complications of vaginal prosthetic surgery
      with transobturator and infracoccygeal support to treat genital urinary prolapse.
      MATERIAL AND METHOD: A prospective and monocentre study was conducted, from
      February 2002 till February 2005. All the patients with or without stress urinary
      incontinence (SUI), who presented either a recurrent prolapse, either a
      voluminous genital prolapse of stage 3 or 4 notably a dominant cystocele, either
      a post-hysterectomy vaginal vault prolapse or even a prolapse of lesser
      importance but in a context of obesity, were operated according to the
      transobturator infracoccygeal sling technique. RESULTS: One hundred and three
      patients with a mean age of 65+/-11 years (41-84) were enrolled, with once on two
      SUI. Thirty percent of the patients had recurrent prolapse and 44% post
      hysterectomy vaginal vault prolapse. With a mean follow-up of 32+/-13 months (12
      53), the success rate of the technique was estimated to be 97% anatomically
      (three failures) and 89% in terms of urinary symptoms (69% of patients were
      cured, 20% were improved and 11% failed). Quality of life of the patients was
      sharply improved and their degree of satisfaction was high. Sexuality of the
      population which was limited here (44% of active patients) did not seem very
      modified by surgery. Complications were represented by a case of urinary
      retention observed with a secondarily pelvic haematoma, a low rectal injury
      without consequence, three blood transfusions. Three patients developed de novo
      overactive bladder. The prostheses exposure rate was 16%, once requiring on two
      one re-intervention. Prostheses were perceived during the postoperative
      evaluation by the examiner for 43% of the patients. But examination was painful
      only in 9,7% of the cases. CONCLUSION: Combined treatment of vaginal prolapse and
      associated urinary incontinence is possible by the use of a single transvaginal
      prosthesis. The medium-term anatomical and functional results are very good. The
      results on continence are good and a subsequent specific procedure is always
      possible in the case of failure or insufficient improvement. The prostheses
      exposure rate is similar to that observed with synthetic transvaginal prostheses.
      The exact tolerance of vaginal prosthetic repair of the prolapse of young women
      being this day an unknown, we remain careful on the extension of the indications
      of this technique in this category of population.

PMID- 17513069
TI  - Changes in the prevalence of non-medical prescription drug use and drug use
      disorders in the United States: 1991-1992 and 2001-2002.
AB  - OBJECTIVE: To examine changes in the prevalence of non-medical prescription drug
      use and DSM-IV non-medical prescription abuse and dependence in the United States
      between 1991-1992 and 2001-2002. METHOD: Comparison of the prevalence of past
      year non-medical prescription drug use and drug use disorders in the total sample
      and among lifetime non-medical users in two large national surveys conducted 10
      years apart. RESULTS: From 1991-1992 to 2001-2002, the prevalence of DSM-IV non
      medical prescription drug use increased by 53%, from 1.5% to 2.3% (p<0.001), and
      the prevalence of drug use disorders increased by 67% from 0.3% to 0.5%
      (p<0.001). The conditional prevalence of a disorder among users increased
      numerically from 19.9% to 23.6%, but this increase was not statistically
      significant (p=0.15). CONCLUSIONS: There have been substantial increases in the
      prevalence of prescription drug non-medical use and prescription drug use
      disorders in the United States. Given the clinical utility of prescription drugs,
      urgent action is needed to find approaches that balance the need for access to
      these medications among those who need them, against their potential for abuse
      and dependence in subgroups of vulnerable individuals.

PMID- 17513070
TI  - Molecular subtype-specific clinical diagnosis of prion diseases.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare transmissible disease caused
      by accumulation of pathological prion protein (PrP(sc)) in the CNS. According to
      the codon 129 polymorphism (methionine or valine) and the prion protein type 1 or
      2, a classification into distinct subtypes was established. Further analysis of
      these subtypes detected atypical clinical forms with longer disease duration or
      younger age at onset. The CJD subtype influences sensitivity of the technical
      investigations such as 14-3-3 in CSF, periodic sharp wave complexes in the EEG or
      hyperintense basal ganglia in MRI. A further characterization of these subtypes
      is important for reliable diagnosis and identification of rare disease variants.
      The aim is to establish specific patterns of test results and clinical findings.
      These improvements in diagnostics may be the reason for the apparent increase in
      sCJD incidence in Germany from 0.9 in 1994 to 1.6 in a million in 2005. Despite
      careful surveillance, no patient with variant CJD has been detected to date in
      Germany. Here we present the data of the CJD surveillance of the last 13 years.
      Additionally, the improvements in diagnostics and differential diagnosis are
      discussed.

PMID- 17513071
TI  - Early assessment of visual function in full term newborns.
AB  - BACKGROUND: The assessment of visual function is part of all the neonatal
      neurological examination but it is often limited to the evaluation of ocular
      movements and the ability to fix and follow a target. AIM OF THE STUDY: To
      develop a simple battery of test items assessing different aspects of visual
      function that could be used as early as 48 h after birth. STUDY DESIGN AND
      SUBJECTS: : The final battery, which has been used in 50 full term low risk
      neonates, includes 9 items assessing ocular motility, both spontaneous and with
      focus on a visual target, fixation and tracking (horizontal, vertical and in an
      arc), the ability to discriminate stripes of different spatial frequency, and
      attention at distance. RESULTS: The battery proved easy to perform and did not
      require long training. The testing did not require a specific setting and was
      easy to use even for infants in incubators. The equipment is small and cleanable.
      CONCLUSION: Our paper suggests that a simple battery, which can be performed in
      5/10 min, can be easily applied and provides useful information on various
      aspects of early neonatal visual function.

PMID- 17513072
TI  - Early versus late cord clamping: effects on peripheral blood flow and cardiac
      function in term infants.
AB  - BACKGROUND: In the debate on the best cord clamping time in newborn infants, we
      hypothesized that late cord clamping enables an increased volemia due to blood
      transfer to the newborn from the placenta. AIM: To assess whether clamping time
      can affect limb perfusion and heart hemodynamics in a group of 22 healthy term
      newborn infants. STUDY DESIGN: A case-control study. SUBJECTS: Eleven early
      clamped (at 30 s) vaginally-delivered newborn infants were compared with eleven
      late-clamped (at 4 min) newborns. OUTCOME MEASURES: The two groups were studied
      using near-infrared spectroscopy and M-mode echocardiography. RESULTS: Late cord
      clamping coincided with a higher hematocrit (median 62% versus 54%) and
      hemoglobin concentration (median 17.2 versus 15 g/dL), whilst there were no
      changes in bilirubin level. Echocardiography showed a larger end-diastolic left
      ventricle diameter (1.7 cm median value versus 1.5) coupled with unvaried
      shortening and ejection fraction values. There were no changes in calf blood
      flow, oxygen delivery, oxygen consumption or fractional oxygen extraction
      calculated from the NIRS measurements, or in foot perfusion index. CONCLUSIONS:
      Our results demonstrated that late cord clamping coincides with an increased
      placental transfusion, expressed by higher hematocrit and hemoglobin values, and
      larger left ventricle diameter at the end of the diastole, with no changes in
      peripheral perfusion or oxygen metabolism.

PMID- 17513073
TI  - Effect of organic or inorganic trace mineral supplementation on follicular
      response, ovulation, and embryo production in superovulated Angus heifers.
AB  - We determined whether source of trace mineral supplementation prior to embryo
      collection affected embryo production and quality. Angus half-sibling heifers
      (n=20) originating from a common herd were assigned to three treatment groups
      using a 3 x 3 latin square design replicated in time (3 x) and space (6 x
      complete and 1x incomplete): (1) heifers received no added mineral to their diet
      (control; n=53); (2) heifers received a commercially available organic mineral
      supplement (organic; n=52); or (3) heifers received an all inorganic mineral
      supplement (inorganic; n=55). All heifers had ad libitum access to hay and were
      fed a supplement containing corn and soybean meal. Treatments were initiated 23
      days prior to embryo recovery. Heifers were given a 45-day adaptation period of
      no mineral supplementation before initiating a new treatment. Ovarian structures
      were evaluated using transrectal ultrasonography to determine the presence and
      number of follicles and CL on each ovary. The mean number of recovered
      ova/embryos was similar among treatments (4.1+/-0.7, 3.8+/-0.7, and 3.3+/-0.7 for
      control, inorganic, and organic treatments, respectively), the number of
      unfertilized oocytes was greater (P<0.05) for inorganic (2.3+/-0.5) and control
      (1.6+/-0.5) treated heifers than organic (0.4+/-0.4) treated heifers. No
      differences among treatments existed for the number of degenerate or transferable
      embryos, but individual heifer influenced the total number of embryos/ova,
      unfertilized ova, and transferable embryos recovered. We conclude that heifer
      accounted for the greatest differences in embryo production and quality. Source
      of trace mineral supplementation did not significantly alter embryo number or
      quality in superovulated purebred Angus heifers fed a well-balanced diet, meeting
      all trace mineral requirements.

PMID- 17513074
TI  - Impact of compression pressure on tablet appearance.
AB  - The color of model tablets deepened and tablet gloss increased with increase in
      compression pressure regardless of colorant type. The possible reasons for these
      phenomena were examined. These observations could not be explained either by
      polymorphic transition of the colorant or by condensation of the colorant during
      compression. Instead, a change in surface roughness was assumed to be the most
      likely reason. The increase in compression pressure made the tablet surface
      smoother. With the increase in the surface smoothness, diffuse reflection
      decreased while specular reflection increased, indicating the opposite relation
      between diffuse and specular reflection as a function of surface roughness. A
      decrease in diffuse reflection results in a deepening of color. In contrast, an
      increase in specular reflection causes an increase in glossiness. Thus, the
      surface roughness seemed to govern gloss and color. The compression pressure
      seems to be one of the most important factors to control tablet appearance.

PMID- 17513075
TI  - Thermosensitive polymers: synthesis, characterization, and delivery of proteins.
AB  - Three triblock copolymers based on the poly(lactide) or poly(lactide-co
      glycolide) and poly(ethylene glycol) or poly(ethylene oxide) blocks were
      synthesized and characterized. The weight average molecular weight and number
      average molecular weight were determined by gel permeation chromatography and
      proton nuclear magnetic resonance spectroscopy, respectively. Fourier transform
      infrared spectroscopy was used to determine the completion of synthesis of
      polymers. Thermoreversible sol-gel transition temperature and concentration were
      determined by an inverted tube method. Two formulations each of three synthesized
      polymers containing 5% (w/v) of lysozyme or bromelain but differing in polymer
      concentrations (20-30%, w/v) were prepared and studied for in vitro release of
      the incorporated protein. In vitro biocompatibility of the delivery systems was
      studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      cell viability assay. Biological activities of lysozyme and bromelain were
      determined by enzyme activity assays. Critical gelling concentrations were found
      in the range of 20-30% (w/v). In vitro biocompatibility study showed that all the
      formulations were biocompatible. Increasing the polymer concentration led to a
      decrease in burst release and extended the in vitro release of proteins.
      Furthermore, biological activities of lysozyme and bromelain in released samples
      were found to be significantly (p<0.05) greater in comparison to the control.
      Thus, the above thermosensitive polymers were able to deliver proteins in
      biologically active forms at a controlled rate for 2-8 weeks.

PMID- 17513076
TI  - Hypoglycemic and hypolipidemic effects of fresh leaf aqueous extract of
      Cymbopogon citratus Stapf. in rats.
AB  - The present study was designed to investigate the hypoglycemic and hypolipidemic
      effects of the single, daily oral dosing of 125-500 mg/kg of fresh leaf aqueous
      extract of Cymbopogon citratus Stapf. (CCi) in normal, male Wistar rats for 42
      days. The average weights of rats per group were taken at 2 weeks interval for 42
      days. On day 43, blood samples from the rats were collected for fasting plasma
      glucose (FPG), total cholesterol, triglycerides, low-density lipoproteins (LDL
      c), very low-density lipoprotein (VLDL-c) and high-density lipoprotein (HDL-c)
      assays through cardiac puncture under halothane anesthesia. Acute oral dose
      toxicity study of CCi was also conducted using limit dose test of the Up and Down
      Procedure statistical program (AOT425StatPgm, Version 1.0) at a dose of 5000
      mg/kg body weight/oral route. Our results showed CCi to lower FPG and lipid
      parameters dose dependently (p<0.05) while raising the plasma HDL-c level
      (p<0.05) in same dose-related fashion but with no effect on plasma triglycerides
      level (p>0.05). Results of acute oral toxicity showed CCi to be of low toxicity
      and as such could be considered relatively safe on acute exposure. Thus,
      confirming its folkloric use and safety in suspected Type 2 diabetic patients.

PMID- 17513077
TI  - Antibacterial activity of Quercus ilex bark's extracts.
AB  - The antibacterial activity of different extracts of Quercus ilex bark (Fagaceae)
      was studied in vitro against seven reference strains of bacteria by using a disc
      diffusion method and agar-dilution method. The ethyl acetate extract (QE), n
      butanol extract (QB) and final aqueous layer (QA) were effective against all
      bacterial strains tested at MICs ranging from 128 to 512 microg/ml. The n-hexane
      extract (QH) and dichloromethane extract (QD) showed no activity.

PMID- 17513078
TI  - Diffusion-weighted imaging evaluation of subtle cerebral microstructural changes
      in intrauterine fetal hydrocephalus.
AB  - OBJECTIVE: Hydrocephalus is an important etiological factor in neurological
      decline. With the advent of fetal ultrasound, fetal hydrocephalus is now more
      frequently detected than in the past. Ultrasonography (USG) provides information
      on general morphology, but microstructural changes that may play a prognostic
      role are beyond the resolution of that technique. These changes may theoretically
      be revealed by diffusion-weighted magnetic resonance imaging (DW-MRI). In this
      study, our preliminary findings of DW-MRI on the hydrocephalic fetuses are
      presented. MATERIALS AND METHODS: Twelve fetuses with fetal USG diagnosis of
      hydrocephalus were investigated using a 1.5-T MR scanner. In addition to
      conventional techniques, DWI was performed. It was obtained using a single-shot
      echo-planar imaging sequence (TR/TE: 4393/81 ms; slice thickness: 5 mm;
      interslice gap: 1 mm; FOV: 230 mm; matrix size: 128x256; b values: 0 and 1000
      s/mm2). Apparent diffusion coefficient (ADC) values were measured in the white
      matter of the periventricular frontal and occipital lobes, basal ganglia,
      thalamus, centrum semiovale and cerebrospinal fluid in the lateral ventricle.
      These values were compared with the normal prenatal ADC values from a
      radiological study published in the literature. RESULTS: All fetuses had moderate
      or severe bilateral supratentorial ventricular dilatation that was compatible
      with hydrocephalus. On conventional T1- and T2-weighted imaging, cerebral
      parenchyma had normal signal pattern and ADC values were significantly lower than
      those reported for fetuses with normal brain. These values were lower in
      hydrocephalic fetuses with statistical significance (P<.05-.01). CONCLUSION: DWI
      is a sensitive technique to investigate cerebral microstructure. The reduction in
      cerebral blood flow and alterations in cerebral energy metabolism in cases with
      hydrocephalus have been shown before. Changes in cerebral blood flow and energy
      metabolism, as a consequence of cerebral compression, may occur in hydrocephalus.
      Elevated ventricular pressure may cause cerebral ischemia. The anaerobic
      glycolysis seen in the hydrocephalic brain tissue by increasing the lactate
      concentration and intracellular fluid flux may be the reason for the reduced ADC
      values in hydrocephalic fetuses. However, long-term prospective trials on the
      correlation of ADC values and neurological outcome are necessary to exploit the
      full benefit of that novel technique.

PMID- 17513079
TI  - [Genetic aspects of obesity].
AB  - Genetic, specifically monogenic, obesity must be suspected: in cases of early
      severe obesity, developing in the first months of life; in cases of severely
      abnormal dietary behavior; in cases of associated endocrine abnormalities or
      pigmentation disorders; in cases of parental consanguinity. Mutations of the MC4R
      gene are the leading cause of oligogenic obesity. Discovery of a mutation of the
      MC4R gene furnishes a biologic source for some patients' susceptibility to
      obesity. Most human obesity nonetheless results from the interaction of multiple
      genetic factors and the environment. Molecules acting on the melanocortin pathway
      are currently under development by the pharmaceutical industry.

PMID- 17513081
TI  - [The challenges of preventing mother-to-child transmission of HIV in Africa].
AB  - HIV (human immunodeficiency virus) is the leading cause of infant mortality in
      Africa where 1700 children are infected each day, principally by mother-to-child
      transmission. Prevention of this risk is therefore a public health priority.
      Considerable progress has been made in the past 10 years in preventing the risk
      of mother-to-child transmission in the peripartum period in Africa: short
      antiretroviral regimens during the third trimester of pregnancy can reduce
      transmission rates to less than 5%. Breast-feeding, which is widespread and
      prolonged in Africa, causes many HIV infections and thus reduces the efficacy of
      peripartum interventions. Interventions that offer alternatives to prolonged
      breast-feeding and are both socially acceptable and safe for the infant can
      effectively reduce the risk of postnatal HIV transmission. But operational
      implementation of these postnatal interventions remains complex. Use of
      antiretroviral agents as prophylaxis for mother and child during the breast
      feeding period and clinical management of breast-feeding mothers with combined
      antiretroviral treatments offer hope that the risk of postnatal HIV transmission
      can be reduced, but the effectiveness and safety of these interventions still
      need to be assessed.

PMID- 17513080
TI  - [Predisposition to infection in patients with pemphigus. Retrospective study of
      141 cases].
AB  - INTRODUCTION: The relation between pemphigus and infection is complex. The aim of
      this work was to determine the frequency and impact of infection as well as the
      factors associated with it among our patients with pemphigus. METHODS: This
      retrospective case series examined records of patients with pemphigus admitted to
      the dermatology unit of Ibn Sina University Hospital of Rabat between 1989 and
      2004. We compared the patients with and without infections as well as the
      patients with and without severe bacterial infections according to patient
      profile and outcome. The principal outcome measure was death and the secondary
      measure, duration of hospitalization. RESULTS: Of the 141 patients with pemphigus
      included in our study, 68% developed an infection. Infections were bacterial in
      52% of cases, fungal in 50%, herpetic in 19% and parasitic in 1.5%. They were
      associated with diabetes mellitus and immunosuppressive drugs. Severe bacterial
      infection was frequent in patients with diabetes and rare in those treated with
      corticosteroids or with pemphigus foliaceous. Death occurred significantly more
      often among infected subjects (p=0.01), especially those with severe bacterial
      infections (p<0.001). Hospitalization was slightly longer among patients with
      infections (p=0.01) but shorter in cases of severe bacterial infections
      (p=0.004). DISCUSSION: Our study confirms the predisposition to all types of
      infection among patients with pemphigus, as well as the undeniable role its
      treatment plays in promoting infection. Severe bacterial infections were most
      often contracted before hospitalization. The literature reports a wide variety of
      infections, with pemphigus-herpes documented most often. Prevention and
      management require hygienic measures as well as early diagnosis and treatment of
      pemphigus and infections. Preventive treatment may be considered, but studies are
      needed to define the patients who might benefit from it.

PMID- 17513082
TI  - Patterns of self-reported symptoms in pancreatic cancer patients receiving
      chemoradiation.
AB  - Pancreatic cancer is a lethal disease characterized by multiple disease-related
      symptoms. Chemoradiation therapy is a standard of treatment for locally advanced
      pancreatic cancer. Although shown to prolong survival, there is little
      information about treatment-related symptoms or the palliative benefits of
      chemoradiation. We assessed symptoms of patients with locally advanced pancreatic
      cancer receiving chemoradiation to determine the prevalence, and co-occurrence,
      of symptoms and to identify the extent to which symptoms interfered with
      function. Forty-eight patients were treated with chemoradiation on a Phase I
      protocol. Patients received radiotherapy (50.4 Gy in 28 fractions), capecitabine
      (median dose 825 mg/m(2) twice daily), and bevacizumab (2.5-10 mg/kg). Symptom
      severity and its interference with function were prospectively assessed (at
      presentation, during, and after chemoradiation) in 43 consenting patients using
      the M.D. Anderson Symptom Inventory. Results showed that 95% of patients reported
      at least one of the 13 symptoms assessed at presentation. The most commonly
      reported symptoms of moderate to severe (>or=5 on a 0-10 scale) intensity at
      presentation were lack of appetite (24%), pain (19%), fatigue (19%), and sleep
      disturbance (10%). We observed an increase in patients reporting moderate to
      severe fatigue, nausea, and sleep disturbance during chemoradiation. McNemar
      tests for paired binary observations showed the proportion of patients reporting
      moderate to severe symptoms significantly (P<0.001) decreased after
      chemoradiation at 94 days follow-up (lack of appetite=7%, pain=7%, fatigue=13%,
      sleep disturbance=7%). This study demonstrates the feasibility and usefulness of
      symptom assessment in chemoradiation protocols. Future studies with larger
      cohorts are needed to further characterize multiple symptoms associated with
      chemoradiation.

PMID- 17513083
TI  - Utility and limitations of a peptide reactivity assay to predict fragrance
      allergens in vitro.
AB  - A key step in the skin sensitization process is the formation of a covalent
      adduct between the skin sensitizer and endogenous proteins and/or peptides in the
      skin. A published peptide depletion assay was used to relate the in vitro
      reactivity of fragrance molecules to LLNA data. Using the classical assay, 22 of
      28 tested moderate to strong sensitizers were positive. The prediction of weak
      sensitizers proved to be more difficult with only 50% of weak sensitizers giving
      a positive response, but for some compounds this could also be due to false
      positive results from the LLNA. LC-MS analysis yielded the expected mass of the
      peptide adducts in several cases, whereas in other cases putative oxidation
      reactions led to adducts of unexpected molecular weight. Several moderately
      sensitizing aldehydes were correctly predicted by the depletion assay, but no
      adducts were found and the depletion appears to be due to an oxidation of the
      parent peptide catalyzed by the test compound. Finally, alternative test peptides
      derived from a physiological reactive protein with enhanced sensitivity for weak
      Michael acceptors were found, further increasing the sensitivity of the assay.

PMID- 17513084
TI  - An in vitro study on 5-HT6 receptor antagonist induced hepatotoxicity based on
      biochemical assays and toxicogenomics.
AB  - We investigated the effects of two 5-HT(6) receptor antagonists on rat primary
      hepatocytes using a combined biochemical and toxicogenomics approach. Both
      compounds share the same pharmacological target, but displayed strikingly
      different toxicity profiles in pre-clinical animal studies: While R7199 caused
      hepatic steatosis in rats, no hepatotoxicity was observed with R0074. Here, we
      partially reproduced the steatosis findings seen in vivo using primary rat
      hepatocytes. Biochemical analyses and gene expression results generally supported
      the findings observed in the animal model and also allowed the differentiation of
      both compounds with regards to hepatotoxic potential. In particular, the
      induction of Cyp 2B and Cyp 3A1 directly correlates to the findings in the livers
      of treated animals. The effects on genes of the steroideogenic pathway relate to
      the deregulation of cholesterol homeostasis. We also observed the inhibition of
      beta-oxidation, indicating impaired lipid metabolism. Hence, gene expression
      analysis in combination with biochemical parameters can provide additional
      insight into the possible mechanisms underlying adverse events.

PMID- 17513085
TI  - Spring: a novel family of miniature inverted-repeat transposable elements is
      associated with genes in apple.
AB  - The apple, Malusxdomestica Borkh., belongs to the family Rosaceae and subfamily
      Maloideae and has a genome size of approximately 750 Mb. In this study, a novel
      family of transposable elements, designated Spring, has been identified in the
      apple genome. The four Spring elements, Spring-1 to Spring-4, share all the
      classic features of miniature inverted-repeat transposable elements (MITEs),
      including small size (approximately 148 bp), no coding potential, A/T richness,
      insertion bias toward noncoding regions, terminal inverted repeats (TIRs), target
      site duplications, and potential for forming secondary structures. Evidence of
      previous mobility of Spring-4 is demonstrated by sequence alignment of genes
      encoding 1-aminocyclopropane-1-carboxylic acid synthase from both apple and a
      related member of the Maloideae subfamily, pear. The Spring elements are flanked
      by either 8- or 9-bp direct repeats, and they differ significantly in size
      compared to other previously reported MITEs in plants. The TIRs of these Spring
      elements are not found in any other previously reported plant genes or
      transposons, except for apple. The possible role of Spring elements in the apple
      genome is discussed.

PMID- 17513086
TI  - Identification and characterization of a MBP isoform specific to hypothalamus in
      orange-spotted grouper (Epinephelus coioides).
AB  - Myelin basic protein (MBP), as a major component of the myelin sheath, has been
      revealed to play an important role in forming and maintaining myelin structure in
      vertebrate nervous system. In teleost, hypothalamus is an instinctive brain
      center and plays significant roles in many physiological functions, such as
      energy metabolism, growth, reproduction, and stress response. In comparison with
      other MBP identified in vertebrates, a smallest MBP is cloned and identified from
      the orange-spotted grouper hypothalamic cDNA plasmid library in this study. RT
      PCR analysis and Western blot detection indicate that the EcMBP is specific to
      hypothalamus, and expresses mainly in the tuberal hypothalamus in adult grouper.
      Immunofluorescence localization suggests that EcMBP should be expressed by
      oligodendrocytes, and the expressing cells should be concentrated in hypothalamus
      and the area surrounding hypothalamus, such as NPOpc, VC, DP, NLTm, and NDLI. The
      studies on EcMBP expression pattern and developmental behaviour in the brains of
      grouper embryos and larvae reveal that the EcMBP-expressing cells are only
      limited in a defined set of cells on the border of hypothalamus, and suggest that
      the EcMBP-expressing cells might be a subpopulation of oligodendrocyte progenitor
      cells. This study not only identifies a smallest MBP isoform specific to
      hypothalamus that can be used as a molecular marker of oligodendrocytes in fish,
      but also provides new insights for MBP evolution and cellular distribution.

PMID- 17513087
TI  - An associative memory readout for ESNs with applications to dynamical pattern
      recognition.
AB  - The use of echo state networks (ESN) to find patterns in time (dynamical pattern
      recognition) has been limited. This paper argues that ESNs are particularly well
      suited for dynamical pattern recognition and proposes a linear associative memory
      (LAM) as a novel readout for ESNs. From the class of LAMs, the minimum average
      correlation energy (MACE) filter is adopted because of its high rejection
      characteristics that allow its use as a detector in the automatic pattern
      recognition literature. In the ESN application, the MACE interprets the states of
      the ESN as a two-dimensional "image", one dimension being time and the other the
      processing element index (space). An optimal template image for each class, which
      associates ESN states with the class label, can be analytically computed using
      training data. During testing, ESN states are correlated with each template image
      and the class label of the template with the highest correlation is assigned to
      the input pattern. The ESN-MACE combination leads to a nonlinear template matcher
      with robust noise performance as needed in non-Gaussian, nonlinear digital
      communication channels. A real-world data experiment for chemical sensing with an
      electronic nose is included to demonstrate the validity of this approach.
      Moreover, the proposed readout can also be used with liquid state machines
      eliminating the need to convert spike trains into continuous signals by binning
      or low-pass filtering.

PMID- 17513088
TI  - Online design of an echo state network based wide area monitor for a multimachine
      power system.
AB  - With deregulation and growth of the power industry, many power system elements
      such as generators, transmission lines, are driven to operate near their maximum
      capacity, especially those serving heavy load centres. Wide Area Controllers
      (WACs) using wide area or global signals can provide remote auxiliary control
      signals to local controllers such as automatic voltage regulators, power system
      stabilizers, etc. to damp out system oscillations. However, since the power
      system is highly nonlinear with fast changing dynamics, it is a challenging
      problem to design an online system monitor/estimator, which can provide dynamic
      intra-area and inter-area information such speed deviations of generators to an
      adaptive WAC continuously. This paper presents a new kind of recurrent neural
      networks, called the Echo State Network (ESN), for the online design of a Wide
      Area Monitor (WAM) for a multimachine power system. A single ESN is used to
      predict the speed deviations of four generators in two different areas. The
      performance of this ESN WAM is evaluated for small and large disturbances on the
      power system. Results for an ESN based WAM and a Time-Delayed Neural Network
      (TDNN)-based WAM are presented and compared. The advantages of the ESN WAM are
      that it learns the dynamics of the power system in a shorter training time with a
      higher accuracy and with considerably fewer weights to be adapted compared to the
      design-based on a TDNN.

PMID- 17513090
TI  - Folate status in women of childbearing age with epilepsy.
AB  - Treatment with cytochrome P450 enzyme-inducing antiepileptic drugs (P450-inducing
      AEDs) is known to interfere with folate metabolism. Low folate status is of
      special concern in women with epilepsy who might become pregnant. Therefore,
      folate status was assessed in women age 16-42 treated for epilepsy. Staple food
      is not folic acid fortified in Norway. Only 1/94 women was folate-deficient by
      the laboratory reference value for serum folate of > 4 nM. Fourteen (15%)
      patients with serum folate values from 5 to 9 nM may be considered folate
      insufficient. Plasma homocysteine was elevated > 13 microM in 2/65 women. These
      findings compare favorably with previous reports. A questionnaire addressing
      factors interfering with folate metabolism was answered by 58 of the women. In
      women who did not use a supplement containing > or =0.2 mg of folic acid
      regularly (n=33), the median serum folate value was lower in those using P450
      inducing AEDs than in those using other AEDs (p=0.023). The interaction between
      P450-inducing AEDs and folate metabolism may be clinically relevant and can be
      balanced by supplementation of small doses of folic acid. The results of this
      survey support the recommendation that women of childbearing age treated with
      AEDs receive folic acid supplementation, particularly those taking P450-inducing
      AEDs.

PMID- 17513091
TI  - Psychotropic drugs use and risk of heat-related hospitalisation.
AB  - OBJECTIVE: To assess if use of psychotropic drugs is associated with an increased
      risk of admission for heat-related pathologies during a heat wave period. METHOD:
      We conducted a matched case-control study. Cases were defined as subjects
      admitted to an emergency department for heat-related pathology (hyperthermia or
      heat stroke) over the August 2003 heat wave. Controls were defined as subjects
      living in the same area but not hospitalised over the same period and who had at
      least one prescription form submitted for refunding by the social security
      insurance in July 2003. Multivariate analyses were used to identify psychotropic
      drugs independently associated with hospital referral during the heat wave
      period. RESULTS: Out of the 1405 patients admitted to the emergency department,
      56 (4%) presented with heat-related pathology. The mean age of cases was 83
      years. Multivariate analyses showed that cases were more likely than controls to
      be treated with anticholinergic drugs (OR 6.0, 95% CI 1.8-19.6), antipsychotics
      (OR 4.6, 95% CI 1.9-11.2) or anxiolytics (OR 2.4, 95% CI 1.3-4.4). CONCLUSION: In
      special risk situations such as heat waves, the risk/benefit ratio of
      psychotropic drugs which could interfere with body temperature regulation has to
      be carefully assessed, particularly in the elderly.

PMID- 17513092
TI  - Current issues in bipolar disorder: a critical review.
AB  - Although awareness on bipolar disorder has increased during the last decade, this
      condition remains characterized by a disabling burden, in terms of morbidity and
      functional impairment. This paper aims to review some critical issues in the
      current knowledge on Bipolar disorder. Although large European epidemiological
      studies are lacking, Bipolar disorder is characterized by a set of severe
      features, including an early age of onset, a chronic outcome and an important
      suicidal risk. A majority of bipolar patients also experience a comorbid Axis I
      condition, including substance abuse, anxiety disorder and attention-deficit
      hyperactivity disorder. This situation presents a therapeutic challenge, since
      antidepressants or methylphenidate may be associated with the risk of inducing
      mania. Recently, a large number of studies have provided evidence for the
      efficacy of new compounds in the treatment of both mania and bipolar depression,
      but also in long-term relapse prevention. Recent research has also allowed for
      the redefinition of the concept of mood stabilizer and for improving existing
      guidelines on the clinical management of Bipolar disorder.

PMID- 17513094
TI  - Controlled growth of calcium oxalate crystal in bicontinuous microemulsions
      containing amino acids.
AB  - The growth of calcium oxalate (CaC(2)O(4)) crystal in water channels of three
      kinds of bicontinuous microemulsions, consisted of P-octyl polyethylene glycol
      phenylether (OP)/n-amyl alcohol/cyclohexane/water and above microemulsions
      containing tryptophan (Trp) or aspartic acid (Asp) has been studied. The products
      were characterized by transmission electron microscopy (TEM), Fourier transform
      infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The results indicated
      that both surfactant and amino acids all could prompt the growth of calcium
      oxalate monohydrate (COM) crystal, but the crystal morphology varied with the
      different microemulsions, pH values of the aqueous solution in channels and
      concentrations of the reactants. Various crystal morphologies such as butterfly
      like, hollow and spiny spherical could be observed easily. A model of molecular
      identification--organized assembly--pervasion-combination balance was proposed to
      explain the formation mechanism of CaC(2)O(4) crystals in the microemulsions
      containing Asp.

PMID- 17513093
TI  - Towards a functional topography of sensory gating areas: invasive P50 recording
      and electrical stimulation mapping in epilepsy surgery candidates.
AB  - The filtering of sensory information, also referred to as "sensory gating", is
      impaired in various neuropsychiatric diseases. In the auditory domain, sensory
      gating is investigated mainly as a response decrease of the auditory evoked
      potential component P50 from one click to the second in a double-click paradigm.
      In order to relate deficient sensory gating to anatomy, it is essential to
      identify the cortical structures involved in the generation of P50. However, the
      exact cerebral topography of P50 gating remains largely unknown. In a group of 17
      patients with drug-resistant focal epilepsy, P50 was recorded invasively via
      subdural electrodes, and the topography of functionally indispensable
      ("eloquent") cortices was obtained by electrical stimulation mapping. These
      eloquent areas were involved in language, motor, and sensory functions. P50 could
      be identified in 13 patients in either temporal (n=8) or midfrontal sites (n=5).
      There were six occurrences (in five patients) of overlap of sites with maximal
      P50 responses and eloquent areas. Those were auditory (n=1), supplementary
      sensorimotor (n=3), primary motor (n=1), and supplementary negative motor (n=1).
      Results suggest that the early stage of sensory gating already involves a top
      down modulation of sensory input by frontal areas.

PMID- 17513095
TI  - Description of two new marine pleurostomatid ciliates, Loxophyllum choii nov.
      spec. and L. shini nov. spec. (Ciliophora, Pleurostomatida) from China.
AB  - The morphology and infraciliature of two pleurostomatid ciliates, Loxophyllum
      choii nov. spec. and L. shini nov. spec., collected from inshore waters and a
      shrimp-culturing pond near Qingdao (Tsingtao), China, were investigated using
      live observations and the protargol-impregnation method. L. choii is
      distinguished from its congeners by the presence of conspicuous warts and
      prominent spines along the dorsal margin. L. shini is identified by a combination
      of characters including the small body size, the presence of two macronuclear
      nodules and the evenly distributed extrusomes whose tips protrude from the
      surface along both margins.

PMID- 17513097
TI  - Energetics of growth in semi-precocial shorebird chicks in a warm environment:
      the African black oystercatcher, Haematopus moquini.
AB  - We studied prefledging growth, energy expenditure and time budgets of African
      Black Oystercatcher, Haematopus moquini, chicks on Robben Island, Western Cape,
      South Africa. The aim of the study was to investigate the effect of parental
      feeding on the growth and energetics of semi-precocial shorebird chicks. Chicks
      reached mean fledging mass, 463 g, in 40 days. The growth rate coefficient of
      African Black Oystercatcher chicks was 2% below the predicted value for a
      shorebird species of their body mass, but it was smaller than that of other
      precocial and semi-precocial shorebirds to date. Resting metabolic rate (RMR,
      measured through respirometry), daily metabolisable energy (DME), defined as
      daily energy expenditure (DEE, measured with doubly labelled water) plus energy
      deposited into tissue (E(tis)), and total metabolisable energy (TME) of African
      Black Oystercatcher chicks were similar to those expected for a species of their
      body size. DEE was not influenced by weather (ambient temperature, operative
      temperature and wind speed), therefore, variations in DEE may be explained by
      body mass alone. The relative RMR of the African Black Oystercatcher was greater,
      their TME was approximately the same, their average daily metabolisable energy
      (ADME) was less, and they spent less time foraging (short periods of parental
      feeding) and more time inactive than three precocial species in the Western Cape.
      Therefore, the semi-precocial mode of development of African Black Oystercatcher
      chicks reduced energy costs from thermoregulation and activity, and they were
      able to grow relatively faster than precocial, self-feeding shorebird species in
      similar climatic conditions. The growth rate coefficient of African Black
      Oystercatcher chicks was smaller than that of Eurasian Oystercatcher, Haematopus
      ostralegus, chicks, which may be a consequence of differences in body size and
      latitudinal effects.

PMID- 17513096
TI  - High plasma D-dimer level is associated with decreased survival in patients with
      lung cancer.
AB  - AIMS: An elevated plasma D-dimer level indicates the activation of coagulation
      and fibrinolysis. In the present study, we investigated the association of pre
      treatment haemostatic parameters (D-dimer, fibrinogen and prothrombin fragment
      1+2) with clinicopathological parameters and outcome in patients with lung
      cancer. MATERIALS AND METHODS: Plasma levels of D-dimer and other parameters were
      measured in 78 evaluable patients with lung cancer (60 non-small cell lung
      cancers, 18 small cell lung cancers). At diagnosis, 35 patients (44.9%) were
      locally advanced stage (IIIA/B) and 43 patients (55.1%) had metastatic disease
      (IV). Multivariate statistical analysis was carried out using Cox's proportional
      hazards model. The receiver operating characteristic curve was used to determine
      the cut-off values for D-dimer, fibrinogen and prothrombin fragment 1+2. RESULTS:
      The median survival for all patients was 264 days (95% confidence interval 200
      328 days). A significant association between the plasma levels of D-dimer and the
      response to chemotherapy was observed (P=0.03). With the univariate analysis,
      tumour stage, pre-treatment plasma levels of D-dimer, fibrinogen, platelet count,
      lactate dehydrogenase concentration and Karnofsky performance status were
      predictive for survival. With the multivariate analysis (P< or =0.1), the plasma
      level of D-dimer (P<0.001), tumour stage (P=0.01) and Karnofsky performance
      status (P=0.02) were identified as independent predictive factors. The median
      survival times were 405 days (95% confidence interval 165-644 days) and 207 days
      (95% confidence interval 146-267 days, P<0.001), respectively, for patients with
      a low D-dimer level (< or =0.65 microg/ml) and a high D-dimer level (>0.65
      microg/ml). CONCLUSIONS: Elevated plasma levels of D-dimer in patients with lung
      cancer are associated with decreased survival and a poor response to treatment.
      Pre-treatment for the D-dimer level may be useful in the prediction of survival
      and the response to treatment.

PMID- 17513098
TI  - Expression of matrilin-2 in oval cells during rat liver regeneration.
AB  - The matrilins represent a new family of oligomeric proteins that are assumed to
      act as adapter molecules connecting other proteins and proteoglycans in the
      extracellular matrix. Matrilin-2, the largest member of the family, displays a
      broad tissue distribution. It incorporates into loose and dense connective tissue
      and becomes associated with some basement membranes. The aim of our study was to
      analyse the expression of matrilin-2 in two liver regeneration models and to
      identify its cellular origin. Liver regeneration was induced in rats by partial
      hepatectomy (PH) and by the 2-acetylaminofluorene (AAF)/partial hepatectomy (PH)
      experimental models. Formalin fixed, paraffin embedded tissue sections were used
      for immunohistochemistry applying a rabbit matrilin-2 polyclonal antibody.
      Matrilin-2 was detected in normal rat liver and partially hepatectomized liver in
      the portal area, but could not be demonstrated in the acini. Matrilin-2 mRNA
      expression was analysed by RT-PCR and in situ hybridization. In the AAF/PH model
      the oval cells but not the hepatocytes produced matrilin-2 mRNA. Increase in
      protein level in the AAF/PH regenerating liver model was demonstrated by Western
      blotting. The protein was present in the basement membrane zone around the
      tubules formed by oval cells. Our data show that hepatic oval cells produce
      matrilin-2, a novel ECM protein, suggesting that matrilin-2 is an important
      component of ECM during stem cell-driven liver regeneration.

PMID- 17513099
TI  - Role of versican and hyaluronan in the differentiation of 3T3-L1 cells into
      preadipocytes and mature adipocytes.
AB  - We have previously shown that during the adipose conversion of these cells the
      culture medium changed its viscoelastic properties due to the presence of
      hyaluronan and a chondroitin sulfate proteoglycan [Calvo, J.C., Rodbard, D.,
      Katki, A., Chernick, S., and Yanagishita, M., 1991. Differentiation of 3T3-L1
      preadipocytes with 3-isobutyl-1-methylxanthine and dexamethasone stimulates cell
      associated and soluble chondroitin 4-sulfate proteoglycans. J. Biol. Chem. 266,
      11237-11244., Calvo, J.C., Gandjbakhche, A.H., Nossal, R., Hascall, V.C., and
      Yanagishita, M., 1993. Rheological effects of the presence of hyaluronic acid in
      the extracellular media of differentiated 3T3-L1 preadipocyte cultures. Arch.
      Biochem. Biophys. 302, 468-475]. Here, we analyze the time course for the
      appearance of these molecules during drug-induced cell differentiation. The
      synthesis of both hyaluronan and the proteoglycan, was maximal at 48 h in the
      presence of isobutylmethylxanthine and dexamethasone, but while hyaluronan
      remained high after changing the culture medium, the proteoglycan dropped to
      almost basal levels after a few days. Northern analysis revealed the presence of
      message for a "versican-like" molecule as well as the possibility of alternative
      splicing. Three major bands of 9.39, 8.48, and 7.69 kb appeared in the analysis.
      These bands showed a dramatic increase in intensity when RNA from non
      differentiated cells was compared to differentiating 3T3-L1 cells. In addition,
      when the time course of appearance for this message was analyzed, it perfectly
      correlated the metabolic labeling of the glycosaminoglycans during cell culture.
      The nucleotide sequencing of two exons revealed between a 100-94% homology with
      proteoglycan PG-M from murine endothelial cells. At least 13% of the proteoglycan
      was able to bind hyaluronan. Disruption of the synthesis of the proteoglycan
      molecule by exogenous addition of xyloside, did not prevent triglyceride
      accumulation but was inhibitory to preconfluent 3T3-L1 cell proliferation.
      Coating of plastic culture dishes with conditioned medium from differentiating
      3T3-L1 cells, resulted in decreased cell adhesion. Cell adhesion was partially
      recovered after degradation of hyaluronan and chondroitin sulfate by enzymatic
      treatment. All these results indicate a possible role of these molecules in the
      observed changes in the viscoelastic properties of the culture medium, as well as
      open the field for a more thorough study of their role in 3T3-L1 cell
      proliferation and/or differentiation.

PMID- 17513100
TI  - Expression and localization of the thromboxane A2 receptor in human nasal mucosa.
AB  - Thromboxane A2 (TXA2) has been thought a potent mediator involved in allergic
      rhinitis, because TXA2 was recovered from the nasal lavage fluid of allergic
      rhinitis patients after allergen provocation and TXA2 receptor antagonists relief
      nasal allergic symptoms. In order to clarify the expression of TXA2 receptor in
      human nasal mucosa, we investigated TXA2 receptor mRNA expression and its protein
      localization by polymerase chain reaction (PCR) and immunohistochemistry,
      respectively. Human turbinates were obtained after turbinectomy from 10 patients
      with nasal obstruction refractory to medical therapy. RT-PCR analysis of total
      RNA from nasal mucosa demonstrated the expression of TXA2 receptor alpha mRNA.
      The immunohistochemical studies revealed that anti-TXA2 receptor alpha antibody
      labeled vascular smooth muscle cells, vascular endothelial cells, epithelial
      cells and submucosal glands in the nasal mucosa. The results may have an
      important clinical implication for understanding the role of TXA2 receptor on
      upper airway diseases such as allergic rhinitis and non-allergic rhinitis.

PMID- 17513101
TI  - No evidence that early use of inhaled corticosteroids reduces current asthma at
      10 years of age.
AB  - BACKGROUND: It is debated whether early treatment with inhaled corticosteroids
      (ICS) can change the natural course of childhood asthma. AIM: To assess if ICS
      treatment before 2 years of age in children with obstructive airways disease
      reduces current asthma at 10 years of age. METHODS: Children with (n=233) and
      without (n=219) recurrent (r) bronchial obstruction (BO) attending clinical
      examination at 2 years of age in the birth cohort Environment and Childhood
      Asthma study in Oslo, were reinvestigated at 10 years of age. Current asthma (CA)
      at 10 years was defined as asthma with either symptoms and/or asthma treatment
      during the last year, and/or 10% fall in forced expired volume in 1s after
      standardized treadmill run. The risk of CA was assessed by logistic regression
      and propensity modelling (including gender, parental atopy and severity score at
      2 years) in children with rBO who received ICS or not by 2 years. RESULTS: CA was
      found in 97 children, more often among rBO children with (56.9%) and without ICS
      treatment (30.8%) compared to no-BO children (5.5%) (p<0.001). In rBO children
      logistic regression analyses (adjusted odds ratio aOR (95% confidence interval))
      identified male gender (aOR 1.82 (1.01-3.27), p=0.046) and severity score at 2
      years 1.14 (1.03-1.28), (p=0.01), as significant and ICS treatment as non
      significant 2.00 (0.98-4.12) risk factors for CA. With propensity modelling
      adjusting for disease severity, ICS treatment by 2 years caused a non-significant
      increased risk aOR of CA of 1.84 (0.89-3.82). CONCLUSION: No evidence was found
      that early use of ICS before age two in children with rBO reduces current asthma
      8 years later.

PMID- 17513102
TI  - Lessons learned from handling a large rural outbreak of Legionnaires' disease:
      Hereford, UK 2003.
AB  - The outbreak of Legionnaires' disease that occurred in Hereford, West Midlands UK
      in 2003 was the single largest outbreak of Legionnaires' in Hereford and one of
      the first to challenge the newly formed Health Protection Agency. This was, de
      facto a 'public health incident' requiring not only the investigation and
      management of a community outbreak of infectious disease, but also one that had
      to take into account other issues including: uncertainty regarding roles and
      responsibilities, political considerations and communication needs including
      sustained media attention. The incident also demonstrated the 'added value' of an
      integrated health protection response. The practical lessons learned from
      outbreaks are rarely described, particularly operational aspects. This paper
      summarises the outbreak, outlines specific elements of the response and
      identifies some of the key learning points for the new Agency and its partners. A
      number of these lessons have a generic applicability to the handling of public
      health incidents.

PMID- 17513103
TI  - Investigation of an outbreak of Legionnaires' disease: Hereford, UK 2003.
AB  - This report describes the investigation and control of a community outbreak of
      Legionnaires' disease in Hereford, UK, in November 2003. Outbreak investigation
      consisted of epidemiological survey, identification and environmental
      investigation of potential sources, microbiological analysis of clinical and
      environmental samples and mapping the location of potential sources and the
      movement and residence of cases. Each identified source was allocated a
      'composite score' based on different zones of exposure and wind direction.
      Altogether, 28 cases were identified, with an overall case fatality rate of 7%.
      All cases had epidemiological links to Hereford city centre. The 'composite
      score' identified a cluster of cooling towers as being the most likely source of
      the outbreak. Environmental samples from one of the cooling towers in the cluster
      and clinical samples from two patients were positive for Legionella pneumophilia
      serogroup 1 and were indistinguishable by molecular sub-typing. In this outbreak,
      the use of microbiological, environmental and epidemiological techniques
      facilitated the rapid identification of a cooling tower as the source of this
      outbreak. This study illustrates the continuing importance of cooling towers as a
      source of Legionnaires' disease and the utility of obtaining and comparing both
      clinical and environmental samples.

PMID- 17513104
TI  - Ion exchange during heavy metal bio-sorption from aqueous solution by dried
      biomass of macrophytes.
AB  - In this study, potentials of oven dried biomass of Eichhornia crassipes,
      Valisneria spiralis and Pistia stratiotes, were examined in terms of their heavy
      metal (Cd, Ni, Zn, Cu, Cr and Pb) sorption capacity, from individual-metal and
      multi-metal aqueous solutions at pH 6.0+/-0.1 (a popular pH of industrial
      effluent). V. spiralis was the most and E. crassipes was the least efficient for
      removal of all the metals. Cd, Pb and Zn were efficiently removed by all the
      three biomass. Cd was removed up to 98% by V. spiralis. Sorption data for Cr, Ni
      and Cd fitted better to Langmuir isotherm equation, while, the sorption data for
      Pb, Zn and Cu fitted better to Freundlich isotherm equation. In general, the
      presence of other metal ions did not influence significantly the targeted metal
      sorption capacity of the test plant biomasses. Ion exchange was proven the main
      mechanism involved in bio-sorption and there was a strong ionic balance between
      adsorbed (H(+) and M(2+)) to the released ions (Na(+) and K(+)) to and from the
      biomass. No significant difference was observed in the metal exchanged amount, by
      doubling of metal concentration (15-30 mg/l) in the solution and employing
      individual-metal and multi-metal solutions.

PMID- 17513105
TI  - Absorption of a mixture of volatile organic compounds (VOCs) in aqueous solutions
      of soluble cutting oil.
AB  - A semi-industrial bioscrubber was developed to treat a complex mixture of VOCs:
      oxygenated, aromatic and chlorinated compounds. In order to optimize the VOCs
      mass transfer, an original washing agent made up of water and cutting oil was
      tested, and the impact of this washing agent on bioscrubbing performances was
      investigated. The results obtained with a laboratory unit show that the addition
      of oil strongly increases the quantity of transferred aromatics. For these
      compounds, the apparent mass transfer coefficient k(L)a is lower than with water
      alone. In term of bioscrubbing performances, comparison of the results obtained
      with the water-oil mixture and water alone showed that the removal efficiency for
      aromatics is enhanced: from 12% to 36% (applied load of 852 g VOCs m(-3)h(-1));
      the elimination of chlorinated compounds is slightly improved. The addition of
      oil does not seem to lead to any dysfunction of the microbial communities that
      metabolize the transferred compounds.

PMID- 17513106
TI  - Bioaugmentation of cyanide-degrading microorganisms in a full-scale cokes
      wastewater treatment facility.
AB  - To enhance biological removal efficiency of total cyanides, bioaugmentation was
      applied to a full-scale cokes wastewaters treatment process. After a laboratorial
      scale cultivation (up to 1.2 m(3)) of a cyanide-degrading yeast (Cryptococcus
      humicolus) and unidentified cyanide-degrading microorganisms, the microbial
      consortium was inoculated into a fluidized-bed type process (1280 m(3)), and then
      enriched for two months with a huge supply of glucose, KCN and other nutrients.
      Target wastewater was effluent of a biological pre-denitrification process for
      treating cokes wastewater, and contained about 14 mg/L of total cyanides in the
      form of ferric cyanide. This may be a first or rare report on the full-scale
      bioaugmentation of specialized-microorganisms. However, continuous operation of
      the full-scale cyanides-degrading bioprocess showed poor removal efficiency than
      expected owing to poor settling performance of microbial flocs, slow
      biodegradation rate of ferric cyanide and lack of organic carbon sources within
      the wastewater. Therefore, there is a need for further studies on how to solve
      these operating problems in full-scale bioaugmentation approach.

PMID- 17513107
TI  - Design, synthesis, and binding studies of bidentate Zn-chelating peptidic
      inhibitors of glyoxalase-I.
AB  - The known affinity of ethyl acetoacetate (ACC) toward divalent zinc prompted us
      to attempt its employment as a chelating moiety in the design of glyoxalase-I
      inhibitors. A practical synthetic route was developed to incorporate this
      pharmacophore into the side chain of glutamic acid, with flexibility to allow
      incorporation of additional functionality at the end-stage of the synthesis.
      Herein, the details of this synthetic approach as well as the evaluation of the
      resultant beta-keto ester compounds are reported.

PMID- 17513108
TI  - 7-Oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamides: synthesis and biological
      activity of a new class of highly potent inhibitors of human cytomegalovirus DNA
      polymerase.
AB  - We report a new class of non-nucleoside antivirals, the 7-oxo-4,7
      dihydrothieno[3,2-b]pyridine-6-carboxamides, some of which possess remarkable
      potency versus a broad spectrum of herpesvirus DNA polymerases and excellent
      selectivity compared to human DNA polymerases. A critical factor in the level of
      activity is hypothesized to be conformational restriction of the key 2-aryl-2
      hydroxyethylamine sidechain by an adjacent methyl group.

PMID- 17513109
TI  - Discovery of pyrazine carboxamide CB1 antagonists: the introduction of a hydroxyl
      group improves the pharmaceutical properties and in vivo efficacy of the series.
AB  - Structure-activity relationships for a series of pyrazine carboxamide CB1
      antagonists are reported. Pharmaceutical properties of the series are improved
      via inclusion of hydroxyl-containing sidechains. This structural modification
      sufficiently improved ADME properties of an orally inactive series such that food
      intake reduction was achieved in rat feeding models. Compound 35 elicits a 46%
      reduction in food intake in ad libidum fed rats 4-h post-dose.

PMID- 17513110
TI  - Design and synthesis of a new, conformationally constrained, macrocyclic small
      molecule inhibitor of STAT3 via 'click chemistry'.
AB  - STAT3 is a promising molecular target for the design of new anticancer drugs. In
      this paper, we report the design and synthesis of a conformationally constrained
      macrocyclic peptidomimetic 2 via click chemistry. Compound 2 was determined to
      bind to STAT3 with a K(i) value of 7.3 microM in a competitive fluorescence
      polarization-based binding assay, representing a promising initial lead compound
      for further optimization.

PMID- 17513111
TI  - The reliability of using accelerometer and gyroscope for gait event
      identification on persons with dropped foot.
AB  - Identification of gait events using an optimal sensor set and a reliable
      algorithm would be useful in the clinical evaluation of patients with dropped
      foot. This article describes a threshold detection method for identifying gait
      events and evaluating the reliability of a system on ten subjects with dropped
      foot and three non-impaired controls. The system comprised three sensor units of
      accelerometers and gyroscopes attached at the thigh, shank and foot of the
      impaired leg in subjects with dropped foot, and the dominant leg in the controls.
      A performance index was devised to compare the values of different measuring
      directions of the sensor units and evaluate the system's reliability. The
      performance index, with the ideal value equal to 1, depended on the
      classification accuracy and timing variation of the turning points. These were
      obtained from the threshold detection method that distinguished the absolute
      maximum and minimum turning points from local maximum and minimum turning points.
      It was found that some specific turning points could effectively identify gait
      events with a high median value in the performance index. These turning points
      included: the minimum turning point in superior-inferior acceleration on the
      thigh at loading response (0.972); the minimum turning point in anterior
      posterior angular velocity on the shank at pre-swing (0.955) and the maximum
      turning point in superior-inferior acceleration on the foot at initial swing
      (0.954). Combining the results of sensor measurements in different orientations
      and attachment locations could be used for gait event identification. It was
      shown that the threshold detection method is reliable. Portable gait-monitoring
      devices can be used for monitoring of daily activities and functional control.

PMID- 17513112
TI  - Synthetic control of interchromophoric interaction in cationic bis-porphyrins
      toward efficient DNA photocleavage and singlet oxygen production in aqueous
      solution.
AB  - We have synthesized cationic bis-porphyrins and their zinc(II) complexes with two
      TMPyP-like chromophores bridged by p- or m-xylylenediamine to develop effective
      DNA photocleaving agents. The xylylene linkers and zinc ion were introduced to
      control interchromophoric interaction that should be involved in
      photosensitization of the cationic bis-porphyrins. The molar absorptivities of
      all the bis-porphyrins in aqueous solution remained unchanged over a wide range
      of concentrations, indicating the absence of self-aggregation property. In
      particular, the molar absorptivity of the zinc(II) complex of the p
      xylylenediamine-linked bis-porphyrin in aqueous solution was 2.0 times as large
      as that of unichromophoric ZnTMPyP, suggesting the absence of both intermolecular
      and intramolecular interchromophoric interaction. The metal-free p
      xylylenediamine-linked bis-porphyrin showed the more efficient conversion ability
      of supercoiled to nicked circular pUC18 plasmid DNA by photosensitization than
      the metal-free m-xylylenediamine-linked one. Furthermore, the zinc complexes of
      the bis-porphyrins exhibited the more potent DNA photocleavage than did the metal
      free bis-porphyrins. Singlet oxygen productivity of the four cationic bis
      porphyrins was determined by measuring the decomposition rate of 1,3
      diphenylisobenzofuran. The amount of singlet oxygen generated by
      photosensitization of the zinc(II) complex of the p-xylylenediamine-linked bis
      porphyrin in aqueous solution was 2.1 times as large as ZnTMPyP, indicating the
      full singlet oxygen productivity. A significant relationship between the DNA
      photocleaving abilities and the singlet oxygen productivities of the cationic
      porphyrins in aqueous solution was found. Hence, the degree of the intramolecular
      interchromophoric interaction, the DNA photocleaving ability, and the singlet
      oxygen productivity of the cationic bis-porphyrins in aqueous solution were
      successfully controlled by means of the introduction of the appropriate linker
      and metal ion.

PMID- 17513113
TI  - The influence of the long chain fatty acid on the antagonistic activities of
      Rhizobium sin-1 lipid A.
AB  - The lipid A from nitrogen-fixing bacterial species Rhizobium sin-1 is
      structurally unusual due to lack of phosphates and the presence of a 2
      aminogluconolactone and a very long chain fatty acid, 27-hydroxyoctacosanoic acid
      (27OHC28:0), moiety. This structurally unusual lipid A can antagonize TNF-alpha
      production by human monocytes induced by Escherichia coli LPS. To establish the
      relevance of the unusual long chain 27-hydroxyoctacosanoic acid for antagonistic
      properties, a highly convergent strategy for the synthesis of several derivatives
      of the lipid A of R. sin-1 has been developed. Compound 1 is a natural R. sin-1
      lipid A having a 27-hydroxyoctacosanoic acid at C-2', compound 2 contains an
      octacosanoic acid moiety at this position, and compound 3 is modified by a short
      chain tetradecanoic acid. Cellular activation studies with a human monocytic cell
      line have shown that the octacosanoic acid is important for optimal antagonistic
      properties. The hydroxyl of the natural 27-hydroxyoctacosanoic moiety does,
      however, not account for inhibitory activity. The resulting structure-activity
      relationships are important for the design of compounds for the treatment of
      septic shock.

PMID- 17513114
TI  - Inducing the replacement of PNA in DNA.PNA duplexes by DNA.
AB  - The uncharged DNA-analogue peptide nucleic acid (PNA) can invade into dsDNA by
      displacing the non-complementary DNA strand. The formed strand displacement
      complexes can create a sterical hindrance to block access of enzymes such as
      nucleases and polymerases. Due to the high stability of DNA.PNA duplexes it is
      usually not possible to displace the PNA strand by ssDNA or ssRNA. We herein
      report that the polycationic, comb-type copolymer alphaPLL-g-Dex can induce such
      a replacement of PNA in DNA.PNA duplexes by ssDNA. The influence of the copolymer
      on strand exchange highly depends on the nature of the oligonucleotides.
      Acceleration has only been observed when both the starting duplex and the single
      stranded exchanger strand were negatively charged. The presented approach should
      allow the withdrawal of PNA induced sterical hindrance of DNA by rehybridisation
      with ssDNA.

PMID- 17513115
TI  - Emission of characteristic fluorescence from the ligand-cytosine complex in
      U_A/ACU bulged RNA duplex.
AB  - Here we show that N,N-bis(3-aminopropyl)-2,7-diamino-1,8-naphthyridine (DANP)
      binds to the single cytosine bulge in RNA duplexes. When the base pairs flanking
      the C-bulge were A-U base pairs, a characteristic fluorescence was emitted from
      the DANP-C-bulge complex. The fluorescence would be useful for detecting the C
      bulge in RNA secondary structures.

PMID- 17513116
TI  - Impact of the PSA-NCAM system on pathophysiology in a chronic rodent model of
      temporal lobe epilepsy.
AB  - Polysialylation is a posttranslational modification of the neural cell adhesion
      molecule (NCAM). In the adult brain, polysialylated NCAM (PSA-NCAM) is restricted
      to regions of neurogenesis and neuroplasticity, where PSA promotes plastic
      changes. Because a variety of plastic changes including neurogenesis have been
      suggested to be functionally involved in the pathophysiology of epilepsies, it is
      of specific interest to define the impact of the PSA-NCAM system on development
      and progression of this disease and associated comorbidities. Here, we studied
      the impact of transient enzymatic depolysialylation of NCAM on the
      pathophysiology in the amygdala kindling model, a chronic rodent model of
      temporal lobe epilepsy. The investigations focused on seizure-induced
      neurogenesis, seizure progression, and on the development of kindling-associated
      changes in behavior and cognition. Loss of PSA decreased the number of
      hippocampal newborn cells that incorporated BrdU during the kindling process and
      the number of new neurons that were ectopically located in the hilus. The
      persistence of basal dendrites has been suggested to be a hallmark of newborn
      granule cells in the epileptic brain. Loss of PSA increased the number of cells
      with persistent basal dendrites. The modification of the hippocampal cell
      proliferation rate and the fate of newborn neurons which occurred as a
      consequence of PSA removal did not affect the generation of a hyperexcitable
      kindled network or associated behavioral changes. Kindling progression was
      comparable in rats with and without removal of PSA. In contrast, loss of PSA
      increased acute seizure susceptibility as indicated by reduced seizure thresholds
      before kindling. The data indicate that hippocampal proliferation rates and
      ectoptic hilar newborn neurons are less critical for epileptic network
      generation. The PSA-NCAM system was not substantiated as a target for
      antiepileptogenic strategies. However, its impact on ectopic newborn neurons
      gives evidence that modulation of PSA-NCAM function may be a strategy to promote
      neuroregeneration in different central nervous system insults.

PMID- 17513117
TI  - Minimally invasive direct coronary artery bypass versus percutaneous coronary
      stenting for stenosis of the left anterior descending artery.

PMID- 17513118
TI  - Sentinel node sampling limits lymphadenectomy in stage I non-small cell lung
      cancer.
AB  - OBJECTIVE: It is controversial whether a systematic mediastinal lymph node
      dissection (MLND) needs to be performed in all patients with stage I lung cancer.
      The present study was done to examine the new sentinel lymph nodes hypothesis
      based on the lobe of the primary tumor. METHODS: In our first study, the lymph
      node (LN) metastases were assessed in 291 stage I non-small cell lung cancer
      (NSCLC) patients who had a major lung resection with a systematic mediastinal
      lymph node dissection. We evaluated the validity of using our new sentinel lymph
      nodes method based on the lobe of the primary tumor as follows: the pretracheal
      (#3), tracheobronchial (#4), and hilar nodes (#10) for right upper lobe tumors;
      #4, subcarinal (#7), and #10 for middle lobe tumors; the subaortic (#5),
      paraaortic (#6), and #10 for left upper lobe tumors; and the #7, #10, and
      interlobar nodes (#11) for tumors in either lower lobes. In the second study, we
      performed a lobectomy with new sentinel node sampling in 64 patients with
      preoperative complications. If all of the sampling nodes showed no metastases on
      frozen section diagnosis, systematic node dissections were not performed.
      RESULTS: Six of 291 patients in the first study had skip metastases that did not
      involve the new sentinel nodes; 5 of the 6 patients had macroscopic pleural
      invasion. Thus, we defined pleural invasion as an exclusion criterion for the
      second study. In the second study, the median follow-up time was 39 months.
      Metastatic lymph nodes were detected in 11 of 64 patients. Fifty-three patients
      (83%) had no metastasis in the sampled nodes, and, therefore, a mediastinal lymph
      node dissection was not done. The morbidity rate in the sampling group was 36%,
      and there was no mortality. In the sampling group, local recurrences were
      observed in two patients, distant metastases in eight, and carcinomatous
      pleuritis in one; the overall 5-year survival rate was 82%. CONCLUSIONS: We found
      that it is possible to perform a less invasive lymphadenectomy for patients with
      stage I lung cancer using intra-operative sampling of new sentinel lymph nodes.

PMID- 17513119
TI  - Complex aortic anomaly with atretic thoracic aorta--extraanatomic conduit
      treatment.

PMID- 17513120
TI  - Preoperative small pulmonary artery did not affect the midterm results of Fontan
      operation.
AB  - OBJECTIVE: It was well discussed, in the primary Fontan era, that small pulmonary
      arterial size could affect the results immediately after the Fontan procedure.
      The objective of the present study is to determine whether this feature remains
      as a risk factor in the era of the staged Fontan completion and poses functional
      impediments in the longer terms. METHODS: Between June 1991 and November 2004,
      the staged Fontan completion was carried out subsequent to the bidirectional
      Glenn procedure in consecutive 57 patients with a preoperative pulmonary artery
      index less than 250 mm2/m2 (Group-S; minimum index 104 mm2/m2). Clinical data
      were reviewed retrospectively. As background and reference information, similar
      data were collected in another consecutive 64 patients with larger pulmonary
      arteries who underwent the staged Fontan completion during the same period (Group
      L; maximum index 697 mm2/m2). RESULTS: No patients died after the Fontan
      procedure in Group-S, while six early deaths in Group-L. No takedown of the
      Fontan circulation was carried out in either group. The latest catheterizations,
      at 2.8+/-2.7 years postoperatively, showed a pulmonary artery index significantly
      lower than the preoperative index (Group-S: 198+/-37-176+/-49 mm2/m2; P=0.0082,
      Group-L: 360+/-94-266+/-89 mm2/m2; P<0.0001). Hemodynamics in Group-S during the
      intermediate term were identical with those in Group-L in mean pulmonary arterial
      pressure (10+/-2 in Group-S and 10+/-3 mmHg in Group-L), mean atrial pressure for
      the systemic chambers (5+/-2 and 6+/-3 mmHg, respectively), mean transpulmonary
      gradient (5+/-2 and 4+/-2 mmHg, respectively), cardiac index (3.0+/-0.7 and 3.0+/
      0.6l/min/m2, respectively), and arterial oxygen saturation (93+/-3% and 94+/-2%,
      respectively). Similarly, brain natriuretic peptides concentration in the serum
      (19.4+/-15.6 in Group-S and 28.3+/-37.2 pg/ml in Group-L) and peak oxygen
      consumption on exercise testing (24.8+/-4.5 and 24.0+/-6.3 ml/kg/min,
      respectively) were not inferior in Group-S to those in Group-L. CONCLUSIONS: The
      outcome after the Fontan completion, including functional ones in the
      intermediate term, was acceptable in patients having a preoperative PA index
      smaller than 250 mm2/m2. Pulmonary artery index decreased still further
      postoperatively, but did not obviously militate against functional efficacy of
      the Fontan circulation.

PMID- 17513121
TI  - Two-photon photodynamic therapy of C6 cells by means of 5-aminolevulinic acid
      induced protoporphyrin IX.
AB  - Photodynamic therapy (PDT) has received increased attention as a treatment
      modality for malignant tumors as well as non-oncologic diseases such as age
      related macular degeneration (AMD). An alternative to excite the photosensitizer
      by the common one-photon absorption is the method of two-photon excitation (TPE).
      This two-photon photodynamic therapy has the potential of improving the
      therapeutic outcome due to a highly localized photodynamic effect. The present
      study investigated the two-photon excited PDT performing in vitro experiments
      where C6 rat glioma cells were irradiated with a pulsed and focused fs
      Ti:sapphire laser emitting light at 800 nm. The irradiance distribution of the
      laser beam was carefully analyzed before the experiment and the applied
      irradiance was known for each position within the irradiated cell layer. Cells
      were divided into four groups and one group was incubated with 5-ALA and
      irradiated 4-5h later. The survival of this group was tested after irradiation by
      means of ethidium bromide and acridine orange staining and compared to a control
      group, which was irradiated under the same conditions, but not incubated with 5
      ALA before. Both groups showed necrotic areas depending on the applied
      irradiance, the value of which at the margin of the necrotic area could be
      deduced from its size. 5-ALA incubated cells became necrotic after irradiation
      with a mean irradiance above 6.1 x 10(10) W/cm(2), while non-incubated cells
      remained viable. Cells of both groups became necrotic when treated with an
      irradiance above 10.9 x 10(10) W/cm(2). The observed affected area of the cell
      layers was between 0.13 mm(2) and 1.10 mm(2). Since the irradiation of non
      incubated cells below the mean power density of 10.9 x 10(10) W/cm(2) induced no
      necrosis, apparently no thermal damage was induced in the cells and necrosis of
      the 5-ALA incubated cells can be ascribed to the photodynamic effect induced by
      two-photon excitation. The successful photodynamic treatment of a large area of a
      monolayer cell culture induced by two-photon excitation offers new perspectives
      for photodynamic treatment modalities.

PMID- 17513122
TI  - Myelin-associated glycoprotein and galactosylcerebroside expression in Schwann
      cells during myelination.
AB  - The temporo-spatial expression profiles of the myelin-associated glycoprotein
      (MAG) and galactosylcerebrosides (Gal-CBs) were analysed during Schwann cell
      differentiation and myelination in Schwann cell cultures and in dorsal root
      ganglion/Schwann cell cocultures. The temporal expression profiles demonstrate
      that the mechanisms triggering and regulating MAG and Gal-CBs are different and
      independent. They also provide further support for a role of MAG, but not Gal
      CBs, in the establishment of the Schwann cell/axon interaction and in the
      formation of the primary mesaxon, while both MAG and Gal-CBs may participate in
      the further maturation of the mesaxon. The spatial expression profiles
      demonstrate that although Gal-CBs are concentrated in the same structures
      (mesaxonal spirals, paranodes and Schmidt-Lanterman incisures) as MAG in both
      developing and mature sheaths, where it is therefore possible that the two might
      have complementary functions, they are also present in regions from which MAG is
      excluded.

PMID- 17513123
TI  - Neurotransmitter phenotype-specific expression changes in developing sympathetic
      neurons.
AB  - During late developmental phases individual sympathetic neurons undergo a switch
      from noradrenergic to cholinergic neurotransmission. This phenomenon of
      plasticity depends on target-derived signals in vivo and is triggered by
      neurotrophic factors in neuronal cultures. To analyze genome-wide expression
      differences between the two transmitter phenotypes we employed DNA microarrays.
      RNA expression profiles were obtained from chick paravertebral sympathetic
      ganglia, treated with neurotrophin 3, glial cell line-derived neurotrophic factor
      or ciliary neurotrophic factor, all of which stimulate cholinergic
      differentiation. Results were compared with the effect of nerve growth factor,
      which functions as a pro-noradrenergic stimulus. The gene set common to all three
      comparisons defined the noradrenergic and cholinergic synexpression groups.
      Several functional categories, such as signal transduction, G-protein-coupled
      signaling, cation transport, neurogenesis and synaptic transmission, were
      enriched in these groups. Experiments based on the prediction that some of the
      identified genes play a role in the neurotransmitter switch identified bone
      morphogenetic protein signaling as an inhibitor of cholinergic differentiation.

PMID- 17513125
TI  - Freeze-drying of live attenuated Vibrio anguillarum mutant for vaccine
      preparation.
AB  - Vibrio anguillarum MVAV6203 is a mutant strain as a candidate of live attenuated
      vaccine. In vaccine preparation, the freeze-drying conditions of the strain were
      investigated to improve the survival after freeze-drying, including the
      protectant, rehydration medium, freezing temperature, and initial cell
      concentration. Vibrio anguillarum MVAV6203 is sensitive to freeze-drying and the
      viability was only 0.03% in the absence of protectant. Of the tested protectants,
      5% trehalose with 15% skimmed milk gave the highest viability of 34.2%. Higher
      cell survival was obtained by quick freezing at -80 degrees C than slow freezing
      at -20 degrees C. Initial cell concentration was another important factor,
      preferable for 1-3 x 10(10)CFU/ml. The supplementation of 10% skimmed milk in
      rehydration medium improved obviously freeze-drying viability. The combination of
      the optimal conditions achieved 51.4% cell viability after freeze-drying.

PMID- 17513124
TI  - Distinct effects of individual opioids on the morphology of spines depend upon
      the internalization of mu opioid receptors.
AB  - This study has examined the relationship between the effects of opioids on the
      internalization of mu opioid receptors (MORs) and the morphology of dendritic
      spines. Several opioids (morphine, etorphine, DAMGO or methadone) were applied to
      cultured hippocampal neurons. Live imaging and biochemical techniques were used
      to examine the dynamic changes in MOR internalization and spine morphology. This
      study reveals that MOR internalization can regulate opioid-induced morphological
      changes in dendritic spines: (1) Chronic treatment with morphine, which induced
      minimal receptor internalization, caused collapse of dendritic spines. In
      contrast, "internalizing" opioids such as DAMGO and etorphine induced the
      emergence of new spines. It reveals that opioid-induced changes in spines vary
      greatly depending on how the applied opioid agonist affects MOR internalization.
      (2) The blockade of receptor internalization by dominant negative mutant of
      dynamin, K44E, reversed the effects of DAMGO and etorphine. It indicates that
      receptor internalization is necessary for the distinct effects of DAMGO and
      etorphine on spines. (3) In neurons that were cultured from MOR knock-out mice
      and had been co-transfected with DsRed and MOR-GFP, morphine caused collapse of
      spines whereas DAMGO induced emergence of new spines, indicating that opioids can
      alter the structure of spines via postsynaptic MORs. (4) Methadone at a low
      concentration induced minimal internalization and had effects that were similar
      to morphine. At a high concentration, methadone induced robust internalization
      and had effects that are opposite to morphine. The concentration-dependent opioid
      induced changes in dendritic spines might also contribute to the variation in the
      effects of individual opioids.

PMID- 17513126
TI  - Expression and purification of bioactive high-purity mouse monokine induced by
      IFN-gamma in Escherichia coli.
AB  - MIG (monokine induced by IFN-gamma) is a CXC-chemokine (CXCL9). It plays
      important roles in regulation of immune activities, and knowledge of the protein
      in areas of allograft transplants, autoimmune diseases, and cancer therapy is
      evolving quickly. The non-tagged recombinant murine MIG (rMuMIG) is therefore
      required to facilitate the functional studies of this important chemokine. Here
      we present the use of a bacteria expression system to produce non-tagged rMuMIG.
      The coding sequence for MIG was cloned into the pET28a (+) vector that was
      transformed into Escherichia coli BL21 (DE3). Expression of rMuMIG was induced by
      IPTG. Bacteria inclusion bodies containing the protein were isolated and washed
      to remove contaminated bacteria proteins, and resolved in Urea buffer.
      Renaturation of the denatured protein was carried out in the defined protein
      refolding buffer, and the refolded protein was purified using S-Sepharose cation
      exchange chromatography. The final preparation of the rMuMIG was more than 99%
      pure as measured by capillary electrophoresis and SDS-PAGE analysis. The
      biological activity of rMuMIG was demonstrated in a murine spleen cell chemotaxis
      assay with ED50 30 ng/ml. Further experiments showed that rMuMIG could inhibit
      proliferation of mouse bone marrow cells in vivo.

PMID- 17513127
TI  - Extrahepatic synthesis of complement components in the rainbow trout
      (Oncorhynchus mykiss).
AB  - The components of activated complement display a wide range of functions in
      inflammatory reactions, including chemotaxis, opsonisation and the destruction of
      microorganisms. In fish, the complement system is believed to be more complex
      than in mammals. Teleost fish possess several complement components encoded by
      multiple genes giving rise to complement subtypes, such as C3-1, C3-3 and C3-4.
      Complement synthesis is mainly localised in the liver and little attention has
      been paid to studying production at extrahepatic sites in fish. In mammalian
      species, the monocyte-macrophage lineage is known to be an important contributor
      to extrahepatic C3 levels. In vitro studies of piscine macrophages have, however,
      revealed absence of basal transcription of C3. The objective of this study was to
      quantify and localise the C3 and C7 subtypes, C4, C5 and factor B in rainbow
      trout using real-time RT-PCR and in situ hybridisation. Widespread extrahepatic
      synthesis of all complement components studied was detected, though with high
      degrees of individual variation between fish. Compared to the levels of
      complement mRNA in the liver, extrahepatic synthesis was low, but indeed high
      enough to imply biological significance. This study represents the first
      comprehensive mapping of the distribution and levels of complement components in
      any vertebrate species.

PMID- 17513128
TI  - Automatic decomposition of multichannel intramuscular EMG signals.
AB  - We describe an automatic algorithm for decomposing multichannel EMG signals into
      their component motor unit action potential (MUAP) trains, including signals from
      widely separated recording sites in which MUAPs exhibit appreciable interchannel
      offset and jitter. The algorithm has two phases. In the clustering phase, the
      distinct, recurring MUAPs in each channel are identified, the ones that
      correspond to the same motor units are determined by their temporal
      relationships, and multichannel templates are computed. In the identification
      stage, the MUAP discharges in the signal are identified using matched filtering
      and superimposition resolution techniques. The algorithm looks for the MUAPs with
      the largest single channel components first, using matches in one channel to
      guide the search in other channels, and using information from the other channels
      to confirm or refute each identification. For validation, the algorithm was used
      to decompose 10 real 6-to-8-channel EMG signals containing activity from up to 25
      motor units. Comparison with expert manual decomposition showed that the
      algorithm identified more than 75% of the total 176 MUAP trains with an accuracy
      greater than 95%. The algorithm is fast, robust, and shows promise to be accurate
      enough to be a useful tool for decomposing multichannel signals. It is freely
      available at http://emglab.stanford.edu.

PMID- 17513129
TI  - Displacement of brain regions in preterm infants with non-synostotic
      dolichocephaly investigated by MRI.
AB  - Regional investigations of newborn MRI are important to understand the appearance
      and consequences of early brain injury. Previously, regionalization in neonates
      has been achieved with a Talairach parcellation, using internal landmarks of the
      brain. Non-synostotic dolichocephaly defines a bi-temporal narrowing of the
      preterm infant's head caused by pressure on the immature skull. The impact of
      dolichocephaly on brain shape and regional brain shift, which may compromise the
      validity of the parcellation scheme, has not yet been investigated. Twenty-four
      preterm and 20 fullterm infants were scanned at term equivalent. Skull shapes
      were investigated by cephalometric measurements and population registration.
      Brain tissue volumes were calculated to rule out brain injury underlying skull
      shape differences. The position of Talairach landmarks was evaluated. Cortical
      structures were segmented to determine a positional shift between both groups.
      The preterm group displayed dolichocephalic head shapes and had similar brain
      volumes compared to the mesocephalic fullterm group. In preterm infants,
      Talairach landmarks were consistently positioned relative to each other and to
      the skull base, but were displaced with regard to the calvarium. The frontal and
      superior region was enlarged; central and temporal gyri and sulci were shifted
      comparing preterm and fullterm infants. We found that, in healthy preterm
      infants, dolichocephaly led to a shift of cortical structures, but did not
      influence deep brain structures. We concluded that the validity of a Talairach
      parcellation scheme is compromised and may lead to a miscalculation of regional
      brain volumes and inconsistent parcel contents when comparing infant populations
      with divergent head shapes.

PMID- 17513130
TI  - Surface rendering-based virtual intraventricular endoscopy: retrospective
      feasibility study and comparison to volume rendering-based approach.
AB  - OBJECTIVE: Virtual endoscopic simulations using volume rendering (VR) have been
      proposed as a tool for training and understanding intraventricular anatomy. It is
      not known whether surface rendering (SR), an alternative to VR, can visualize
      intraventricular and subependymal structures better and thus making the virtual
      endoscope more useful for simulating the intraventricular endoscopy. We sought to
      develop SR-virtual endoscopy and compared the visibility of anatomical structures
      in SR and VR using retrospective cases. MATERIALS AND METHODS: Fourteen patients
      who underwent endoscopic intraventricular surgery of third ventricle enrolled the
      study. SR-virtual endoscopy module was developed in open-source software 3D
      Slicer and virtual endoscopic scenes from the retrospective cases were created.
      VR virtual endoscopy of the same cases was prepared in commercial software. Three
      neurosurgeons scored the visibility of substructures in lateral and third
      ventricle, arteries, cranial nerves, and other lesions Results: We found that VR
      and SR-virtual endoscopy performed similarly in visualization of substructures in
      lateral and third ventricle (not significant statistically). However, the SR was
      statistically significantly better in visualizing subependymal arteries, cranial
      nerves, and other lesions (p<0.05, respectively). CONCLUSIONS: We concluded that
      SR-virtual endoscopy is a promising tool to visualize critical anatomical
      structures in simulated endoscopic intraventricular surgery. The results lead us
      to propose a hybrid technique of volume and surface rendering to balance the
      strength of surface rendering alone in visualizing arteries, nerves and lesions,
      with fast volume rendering of third and lateral ventricles.

PMID- 17513132
TI  - Sexual dimorphism of brain developmental trajectories during childhood and
      adolescence.
AB  - Human total brain size is consistently reported to be approximately 8-10% larger
      in males, although consensus on regionally specific differences is weak. Here, in
      the largest longitudinal pediatric neuroimaging study reported to date (829 scans
      from 387 subjects, ages 3 to 27 years), we demonstrate the importance of
      examining size-by-age trajectories of brain development rather than group
      averages across broad age ranges when assessing sexual dimorphism. Using magnetic
      resonance imaging (MRI) we found robust male/female differences in the shapes of
      trajectories with total cerebral volume peaking at age 10.5 in females and 14.5
      in males. White matter increases throughout this 24-year period with males having
      a steeper rate of increase during adolescence. Both cortical and subcortical gray
      matter trajectories follow an inverted U shaped path with peak sizes 1 to 2 years
      earlier in females. These sexually dimorphic trajectories confirm the importance
      of longitudinal data in studies of brain development and underline the need to
      consider sex matching in studies of brain development.

PMID- 17513131
TI  - Volumetric cerebral characteristics of children exposed to opiates and other
      substances in utero.
AB  - Morphometric cerebral characteristics were studied in children with prenatal poly
      substance exposure (n=14) compared to controls (n=14) without such exposure. Ten
      of the substance-exposed children were born to mothers who used opiates (heroin)
      throughout the pregnancy. Groups were compared across 16 brain measures: cortical
      gray matter, cerebral white matter, hippocampus, amygdala, thalamus, accumbens
      area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white
      matter, lateral ventricles, inferior lateral ventricles, and the 3rd and 4th
      ventricles. In addition, continuous measurement of thickness across the entire
      cortical mantle was performed. Volumetric characteristics were correlated with
      ability and questionnaire assessments 2 years prior to scan. Compared to
      controls, the substance-exposed children had smaller intracranial and brain
      volumes, including smaller cerebral cortex, amygdala, accumbens area, putamen,
      pallidum, brainstem, cerebellar cortex, cerebellar white matter, and inferior
      lateral ventricles, and thinner cortex of the right anterior cingulate and
      lateral orbitofrontal cortex. Pallidum and putamen appeared especially reduced in
      the subgroup exposed to opiates. Only volumes of the right anterior cingulate,
      the right lateral orbitofrontal cortex and the accumbens area, showed some
      association with ability and questionnaire measures. The sample studied is rare
      and hence small, so conclusions cannot be drawn with certainty. Morphometric
      group differences were observed, but associations with previous behavioral
      assessment were generally weak. Some of the volumetric differences, particularly
      thinner cortex in part of the right lateral orbitofrontal cortex, may be
      moderately involved in cognitive and behavioral difficulties more frequently
      experienced by opiate and poly-substance-exposed children.

PMID- 17513133
TI  - Top-down task effects overrule automatic multisensory responses to letter-sound
      pairs in auditory association cortex.
AB  - In alphabetic scripts, letters and speech sounds are the basic elements of
      correspondence between spoken and written language. In two previous fMRI studies,
      we showed that the response to speech sounds in the auditory association cortex
      was enhanced by congruent letters and suppressed by incongruent letters.
      Interestingly, temporal synchrony was critical for this congruency effect to
      occur. We interpreted these results as a neural correlate of letter-sound
      integration, driven by the learned congruency of letter-sound pairs. The present
      event-related fMRI study was designed to address two questions that could not
      directly be addressed in the previous studies, due to their passive nature and
      blocked design. Specifically: (1) to examine whether the enhancement/suppression
      of auditory cortex are truly multisensory integration effects or can be explained
      by different attention levels during congruent/incongruent blocks, and (2) to
      examine the effect of top-down task demands on the neural integration of letter
      sound pairs. Firstly, we replicated the previous results with random stimulus
      presentation, which rules out an explanation of the congruency effect in auditory
      cortex solely in terms of attention. Secondly, we showed that the effects of
      congruency and temporal asynchrony in the auditory association cortex were absent
      during active matching. This indicates that multisensory responses in the
      auditory association cortex heavily depend on task demands. Without task
      instructions, the auditory cortex is modulated to favor the processing of
      congruent and synchronous information. This modulation is overruled during
      explicit matching when all audiovisual stimuli are equally relevant, independent
      of congruency and temporal relation.

PMID- 17513134
TI  - Structure of WM bundles constituting the working memory system in early multiple
      sclerosis: a quantitative DTI tractography study.
AB  - Working memory impairment is frequently observed in patients with early multiple
      sclerosis (MS). MRI and functional MRI studies have shown that working memory
      impairment is mostly due to diffuse white matter (WM) damage affecting the
      connectivity between distant cortical areas. However, working memory deficits in
      early MS patients can be either completely or partly masked by compensatory
      functional plasticity. It seems likely that concomitantly with the WM bundle
      injury resulting from pathological processes, the functional plasticity present
      in early MS patients may be accompanied by reactive structural WM plasticity.
      This structural plasticity may effectively compensate for connectivity
      disturbances and/or contribute to functional brain reorganization. The diffusion
      characteristics of WM bundles involved in working memory were assessed here by
      performing quantitative diffusion tensor imaging (DTI) tractography on 24
      patients with early relapsing-remitting MS and 15 healthy control subjects. The
      DTI tractography findings showed that WM connections constituting the executive
      system of working memory were structurally impaired (the fractional anisotropy
      was lower than normal and the mean diffusivity, higher than normal). A
      significantly larger number of connections between the left and right thalami was
      concurrently observed in the MS patients than in the control subjects, which
      suggests that the WM is endowed with reactive structural plasticity.

PMID- 17513135
TI  - Patterns of co-evolution between trypanosomes and their hosts deduced from
      ribosomal RNA and protein-coding gene phylogenies.
AB  - Trypanosomes (genus Trypanosoma) are widespread blood parasites of vertebrates,
      usually transmitted by arthropod or leech vectors. Most trypanosomes have
      lifecycles that alternate between a vertebrate host, where they exist in the
      bloodstream, and an invertebrate host, where they develop in the alimentary
      tract. This raises the question of whether one type of host has had greater
      influence on the evolution of the genus. Working from the generally accepted view
      that trypanosomes are monophyletic, here we examine relationships between
      trypanosomes using phylogenies based on the genes for the small subunit ribosomal
      RNA (SSU rRNA) and the glycosomal glyceraldehyde phosphate dehydrogenase
      (gGAPDH). New analysis of a combined dataset of both these genes provides strong
      support for many known clades of trypanosomes. It also resolves the deepest split
      within the genus between the Aquatic clade, which mainly contains trypanosomes of
      aquatic and amphibious vertebrates, and a clade of trypanosomes from terrestrial
      vertebrates. There is also strengthened support for two deep clades, one
      comprising a wide selection of mammalian trypanosomes and a tsetse fly
      transmitted reptilian trypanosome, and the other combining two bird trypanosome
      subclades. Considering the vertebrate and invertebrate hosts of each clade, it is
      apparent that co-speciation played little role in trypanosome evolution. However
      most clades are associated with a type of vertebrate or invertebrate host, or
      both, indicating that 'host fitting' has been the principal mechanism for
      evolution of trypanosomes.

PMID- 17513136
TI  - Repair of full-thickness rotator cuff tears is recommended regardless of tear
      size and age: a retrospective study of 218 patients.
AB  - Conservative therapy has been recommended for the treatment of a chronic cuff
      lesion with relatively good results. However, recent reports about operative
      treatment of cuff lesions have yielded more favorable results. Although the
      current literature seems to favor early treatment, there is an ongoing debate
      about the timing of the operation. During a 16-year period, 415 chronic full
      thickness rotator cuff tears were operated on at our institution. The indication
      for operative treatment was persistent, severe or moderate pain at rest and
      impairment of shoulder function after initial conservative treatment. At follow
      up, the symptoms were assessed by an interview, and all patients were clinically
      examined. Pain, function, range of active forward flexion, active abduction,
      strength (manual muscle testing), and patient satisfaction were recorded, and the
      results were evaluated by the University of California, Los Angeles shoulder
      rating scale. On the basis of our results, we recommend operative treatment of
      the rotator cuff for all cases in which the tear is full thickness, regardless of
      tear size, if patients have any symptoms, especially pain.

PMID- 17513137
TI  - Estimation of mechanical properties of articular cartilage with MRI - dGEMRIC, T2
      and T1 imaging in different species with variable stages of maturation.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is one of the most potential methods
      for non-invasive diagnosis of cartilage disorders. Several methods have been
      established for clinical use; T(1) relaxation time imaging with negatively
      charged contrast agent (delayed gadolinium enhanced MRI of cartilage, dGEMRIC)
      has been shown to be sensitive to proteoglycan (PG) content while T(2) relaxation
      time has been demonstrated to express properties of the collagen fibril network.
      The use of native T(1) relaxation time has received less attention. OBJECTIVE: In
      the present study, magnetic resonance (MR) parameters of different types of
      patellar cartilage were studied with respect to the mechanical properties of the
      tissue. The general usefulness of the parameters to predict mechanical properties
      was investigated using cartilage from different species and stages of maturation.
      METHODS: dGEMRIC, T(2) and native T(1) relaxation times of healthy mature human,
      juvenile porcine and juvenile bovine articular cartilage samples were measured at
      9.4T at 25 degrees C. Mechanical properties (Young's modulus and dynamic modulus)
      of the samples were measured in unconfined compression using a material testing
      device. The relationships between MRI and mechanical parameters and potential
      differences between different types of tissues were tested statistically.
      RESULTS: Significant, but varying relationships were established between T(1) or
      T(2) relaxation time and mechanical properties, depending on tissue type. The
      values of mechanical parameters were in line with the results previously reported
      in the literature. Unexpectedly, dGEMRIC showed no statistically significant
      association with the mechanical properties. Variation in the assumption of native
      T(1) value did not induce significant differences in the calculated contrast
      agent concentration, and consequently did not affect prediction of mechanical
      properties. CONCLUSION: For patellae, a complex variation in the relationships
      between T(2) and mechanical properties in different groups was revealed. The
      results support the conclusion that juvenile animal tissue, exhibiting a highly
      complex collagenous architecture, may not always serve as a realistic model for
      mature human tissue with a typical three-zone network organization, and other
      than bulk metrics are required for the analysis of cartilage T(2). As the
      multilayered collagen network can strongly control the mechanical characteristics
      of juvenile tissue, it may mask the mechanical role of PGs and explain why
      dGEMRIC could not predict mechanical parameters in patellar cartilage.

PMID- 17513138
TI  - Ketamine "unlocks" the reduced clock-speed effects of cocaine following extended
      training: evidence for dopamine--glutamate interactions in timing and time
      perception.
AB  - The present study examined the clock-speed modulating effects of acute cocaine
      administration in groups of male rats that received different amounts of baseline
      training on a 36-s peak-interval procedure prior to initial drug injection. After
      injection of cocaine (10, 15, or 20mg/kg, ip), rats that had received a minimal
      amount of training (e.g., <or=30 sessions) prior to drug administration displayed
      a horizontal leftward shift in their timing functions indicating that the speed
      of the internal clock was increased. In contrast, rats that had received an
      extended amount of training (e.g., >or=180 sessions) prior to cocaine (15 mg/kg,
      ip) administration did not produce this "classic" curve-shift effect, but instead
      displayed a general disruption of temporal control following drug administration.
      Importantly, when co-administered with a behaviorally ineffective dose of
      ketamine (10mg/kg, ip) the ability of cocaine to modulate clock speed in rats
      receiving extended training was restored. A glutamate "lock/unlock" hypothesis is
      used to explain the observed dopamine-glutamate interactions as a function of
      timing behaviors becoming learned habits.

PMID- 17513139
TI  - Prophage-like gene transfer agents-novel mechanisms of gene exchange for
      Methanococcus, Desulfovibrio, Brachyspira, and Rhodobacter species.
AB  - Gene transfer agents (GTAs) are novel mechanisms for bacterial gene transfer.
      They resemble small, tailed bacteriophages in ultrastructure and act like
      generalized transducing prophages. In contrast to functional prophages, GTAs
      package random fragments of bacterial genomes and incomplete copies of their own
      genomes. The packaged DNA content is characteristic of the GTA and ranges in size
      from 4.4 to 13.6kb. GTAs have been reported in species of Brachyspira,
      Methanococcus, Desulfovibrio, and Rhodobacter. The best studied GTAs are VSH-1 of
      the anaerobic, pathogenic spirochete Brachyspira hyodysenteriae and RcGTA of the
      nonsulfur, purple, photosynthetic bacterium Rhodobacter capsulatus. VSH-1 and
      RcGTA have likely contributed to the ecology and evolution of these bacteria. The
      existence of GTAs in phylogenetically diverse bacteria suggests GTAs may be more
      common in nature than is now appreciated.

PMID- 17513140
TI  - Delayed upstream migration of an iliac stent.
AB  - INTRODUCTION: Stent migrations are described after peripheral endovascular
      treatments. We report a case of an unusual iliac stent movement after a
      successful angioplasty. REPORT: An occlusive distal intimal flap after aorto
      iliac endoarterectomy was successfully fixed by stenting of the left external
      iliac artery. One month later, the patient was readmitted due to contralateral
      limb acute ischemia. Angiography revealed a right iliac artery thrombosis due to
      upstream stent migration from the left external iliac artery into the right
      common iliac artery. The patient underwent a combined surgical and endovascular
      rescue technique. CONCLUSION: Turbulent and pulsatile flow, associated with wall
      remodelling may explain this unexpected complication.

PMID- 17513141
TI  - Photodynamic therapy reduces intimal hyperplasia in prosthetic vascular bypass
      grafts in a pig model.
AB  - BACKGROUND: Bypass surgery has a failing frequency of 30% during the first year,
      mainly due to intimal hyperplasia (IH). This negative effect is most pronounced
      in artificial grafts. Photodynamic therapy (PDT) is a technique in which light
      activates photosensitizer dyes to produce free-radicals resulting in an
      eradication of cells in the vascular wall. The aim of this study was to determine
      the effectiveness of PDT to reduce IH in a preclinical porcine PTFE bypass model.
      MATERIAL AND METHODS: Ten pigs were used. After a pilot PDT dosimetry study (n=3)
      PTFE grafts were bilaterally placed into the circulation as bypasses from the
      common to the external iliac arteries (n=7). The right sides served as controls
      (C). Before implantation of the left grafts, the arterial connecting sites of the
      left distal anastomoses were PDT-treated. The arteries were pressurized at 180
      mmHg for 5 minutes with the photosensitizer Methylene Blue (330 microg/ml), and
      thereafter endoluminally irradiated with laser light (lambda = 660 nm, 100
      mW/cm(2), 150 J/cm(2)). After 4 weeks the specimens were retrieved and formalin
      fixed. Cross sections through the midportions of the distal anastomoses and the
      grafts were used for histology, immunohistochemistry to identify inflammatory
      cells and morphometric evaluation (n=7). RESULTS: No systemic side effects and no
      graft occlusions were noted. PDT-treated anastomoses showed reduced IH in the mid
      portions of the anastomoses (Area of IH: microm(2)/microm graft: C: 6970+/-1536,
      PDT: 2734+/-2560; P<0.005) as well as in the grafts (C: 5391+/-4031, PDT: 777+/
      1331; P<0.02). The number of inflammatory cells per microscopic field was
      increased after PDT (C: 24+/-16, PDT: 37+/-15; P<0.009). CONCLUSIONS: Adjuvant
      PDT, performed in an endovascular fashion, was a safe method to reduce prosthetic
      graftstenosis in a preclinical setting. This study underscores the clinical
      potential of PDT to inhibit the development of clinical bypass graftstenosis.

PMID- 17513142
TI  - Closure of the cribriform fascia: an efficient anatomical barrier against
      postoperative neovascularisation at the saphenofemoral junction? A prospective
      study.
AB  - BACKGROUND: Neovascularisation at the sapheno-femoral junction (SFJ) ligation
      site in the groin may occur within one year after great saphenous vein (GSV)
      surgery. Several anatomical and prosthetic barrier techniques have been proposed
      to prevent this evolution. OBJECTIVE: A prospective study examined whether
      closing the cribriform fascia could reduce the incidence of postoperative
      neovascularisation in the groin. PATIENTS AND METHODS: Patients with primary
      varicose veins and incompetence at the level of the SFJ were included. After SFJ
      ligation in 235 limbs of 193 patients an anatomical barrier was constructed by
      closing the cribriform fascia. Postoperative duplex scanning was performed after
      2 and 12 months. Results were compared with historical control groups in which
      either a silicone patch saphenoplasty or no barrier technique had been performed.
      RESULTS: After one year, 10 limbs had developed recurrent thigh varicose veins
      and duplex scan showed neovascularisation at the SFJ ligation site in 15 of 223
      re-examined limbs (6.7%). This was comparable to the group of 191 limbs with
      silicone patch saphenoplasty (5.2%) (P=0.526) and superior to the group of 189
      limbs without barrier (14.8%) (P<0.01). CONCLUSION: Interposition of an
      anatomical barrier by closing the cribriform fascia after SFJ ligation reduced
      ultrasound detected neovascularisation at the SFJ after one year. In primary
      varicose vein operations application of an anatomical barrier technique (without
      prosthetic patch) is an alternative option to prevent postoperative
      neovascularisation.

PMID- 17513143
TI  - Quercetin, a flavonoid antioxidant, modulates endothelium-derived nitric oxide
      bioavailability in diabetic rat aortas.
AB  - The present work examined the effect of chronic oral administration of quercetin,
      a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress
      in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into
      euglycemic, untreated diabetic, vehicle (1% w/v methylcellulose)-treated
      diabetic, which served as control, or quercetin (10mgkg(-1) body weight)-treated
      diabetic groups and treated orally for 6 weeks. Quercetin treatment reduced blood
      glucose level in diabetic rats. Impaired relaxations to endothelium-dependent
      vasodilator acetylcholine (ACh) and enhanced vasoconstriction responses to
      alpha(1)-adrenoceptor agonist phenylephrine (PE) in diabetic rat aortic rings
      were restored to euglycemic levels by quercetin treatment. Pretreatment with
      N(omega)-nitro-l-arginine methyl ester (l-NAME, 10microM) or methylene blue
      (10microM) completely blocked but indomethacin (10microM) did not affect
      relaxations to ACh in aortic rings from vehicle- or quercetin-treated diabetic
      rats. PE-induced vasoconstriction with an essentially similar magnitude in
      vehicle- or quercetin-treated diabetic rat aortic rings pretreated with l-NAME
      (10microM) plus indomethacin (10microM). Quercetin treatment reduced plasma
      malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HNE) content as well as increased
      superoxide dismutase activity and total antioxidant capacity in diabetic rats.
      From the present study, it can be concluded that quercetin administration to
      diabetic rats restores vascular function, probably through enhancement in the
      bioavailability of endothelium-derived nitric oxide coupled to reduced blood
      glucose level and oxidative stress.

PMID- 17513144
TI  - New approach to the treatment of blinding ocular diseases in animals.

PMID- 17513145
TI  - Canine coronavirus inactivation with physical and chemical agents.
AB  - Canine coronavirus (CCoV) is responsible for mild or moderate enteritis in
      puppies. The virus is highly contagious and avoiding contact with infected dogs
      and their excretions is the only way to ensure disease prevention. Since no
      studies have yet focused on the sensitivity of CCoV to chemical biocides the
      present investigation examined the efficiency of physical and chemical methods of
      viral inactivation. CCoV infectivity was stable at +56 degrees C for up to 30
      min, but tended to decrease rapidly at +65 degrees C and +75 degrees C.
      Germicidal ultra-violet (UV-C) light exposure demonstrated no significant effects
      on virus inactivation for up to 3 days. CCoV was observed to be more stable at pH
      6.0-6.5 while extreme acidic conditions inactivated the virus. Two tested
      aldehydes inactivated the virus but their action was temperature- and time
      dependent. The methods for CCoV inactivation could be applied as animal models to
      study human coronavirus infection, reducing the risk of accidental exposure of
      researchers to pathogens during routine laboratory procedures.

PMID- 17513146
TI  - Pain: a developing issue in veterinary medicine.

PMID- 17513147
TI  - Demonstration of the articular cartilage of the canine ulnar trochlear notch
      using high-field magnetic resonance imaging.
AB  - The articular cartilage covering the ulnar trochlear notch (UTN) of both elbow
      joints from 25 adult canine cadavers was demonstrated by the use of high-field
      magnetic resonance imaging (MRI) with a fat-suppressed, three-dimensional,
      spoiled gradient echo sequence. The dogs used for this study were divided into
      five groups: giant, large, mid-sized, small, and chondrodystrophic breeds. The
      distribution of articular cartilage of the UTN was assessed on MR images. The
      joints were then opened, and the distribution of the articular cartilage of the
      UTN was verified. In 29/50 joints, there was good agreement between gross
      findings of the distribution of the articular cartilage of the UTN and MRI
      interpretation. Reasons for the poor results in small and chondrodystrophic
      breeds were decreased thickness of the articular cartilage, small size of the
      articular surface and of its structural features, and the frequent inability to
      visualize the joint space.

PMID- 17513148
TI  - Homo- and heteronuclear 2D NMR approaches to analyse a mixture of deuterated
      unlike/like stereoisomers using weakly ordering chiral liquid crystals.
AB  - We describe several homo- and heteronuclear 2D NMR strategies dedicated to the
      analysis of anisotropic (2)H spectra of a mixture of dideuterated unlike/like
      stereoisomers with two remote stereogenic centers, using weakly orienting chiral
      liquid crystals. To this end, we propose various 2D correlation experiments,
      denoted "D(H)(n)D" or "D(H)(n)C" (with n=1, 2), that involve two heteronuclear
      polarization transfers of INEPT-type with one or two proton relays. The
      analytical expressions of correlation signals for four pulse sequences reported
      here were calculated using the product-operators formalism for spin I=1 and
      S=1/2. The features and advantages of each scheme are presented and discussed.
      The efficiency of these 2D sequences is illustrated using various deuterated
      model molecules, dissolved in organic solutions of polypeptides made of poly
      gamma-benzyl-L-glutamate (PBLG) or poly-epsilon-carbobenzyloxy-L-lysine (PCBLL)
      and NMR numerical simulations.

PMID- 17513149
TI  - Sensory processing in the fast electrosensory pathway of pulse gymnotids studied
      at multiple integrative levels.
AB  - Pulse gymnotids extract information about the environment using the pulsed
      discharge of an electric organ. Cutaneous electroreceptor organs transduce and
      encode the changes that objects imprint on the self-generated transcutaneous
      electric field. This review deals with the role of a neural circuit, the fast
      electrosensory path of pulse gymnotids, in the streaming of self generated
      electrosensory signals. The activation of this path triggers a low-responsiveness
      window slightly shorter than the interval between electric organ discharges. This
      phenomenon occurs at the electrosensory lateral line lobe where primary afferent
      terminals project on the somata of spherical neurons. The main subservient
      mechanism of the low-responsiveness window rely on the intrinsic properties of
      spherical neurons (dominated by a voltage dependent, low-threshold, non
      inactivating and slowly-deactivating K(+) conductance) determining the cell to
      respond with a single spike followed by a long refractory period. Externally
      generated signals that randomly occur within the interval between self-generated
      discharges are likely blocked by the low responsiveness window. Repetitive
      signals, as those emitted by conspecifics with a slightly lower rate, occur
      progressively at longer delays beyond the duration of the low responsiveness
      window. Transient increases of the discharge rate relocate the interference
      within the low-responsiveness window. We propose that this combination of sensory
      filtering and electromotor control favors the self-generated signals in detriment
      of other, securing the continuity of the electrolocation stream.

PMID- 17513150
TI  - Regulation of interleukin-8 expression in human prostate cancer cells by insulin
      like growth factor-I and inflammatory cytokines.
AB  - OBJECTIVE: Since serum IGF-I levels are related to risks of prostate cancer and
      cytokines like interleukin (IL)-6 and IL-8 have been implicated in prostate
      cancer progression, we investigated the effects of IGF-I on IL-6 and IL-8
      expression in the prostate cancer cell. DESIGN: In order to address the
      regulation by IGF-I of cytokine expression in prostate cancer cells we used cell
      cultures of established androgen dependent (LNCaP) and androgen-independent cell
      lines (DU-145 and PC-3). RESULTS: We found that IGF-I stimulates IL-8 mRNA
      expression and secretion in DU-145 cells, whereas the secretion of IL-6 was
      hardly affected. IGF-I enhances IL-8 expression in synergy with IL-1beta, but not
      with tumour necrosis factor (TNF)alpha. Similarly, on IL-8 promoter activity, IGF
      I exerted synergistic effects with IL-1beta, but not with TNFalpha. Although IGF
      I stimulated the phosphorylation of both Akt (protein kinase B) and extracellular
      regulated kinase (ERK), the effect of IGF-I at IL-8 expression was inhibited only
      by U0126, a pharmacological inhibitor of MAPK/ERK kinase (MEK) and not by
      inhibition of the upstream activator of Akt, phosphatidylinositol-3 kinase
      (PI3K). CONCLUSIONS: Our results indicate that IGF-I stimulates IL-8 expression
      through the MEK-ERK pathway in DU-145 cells, at least in part, by augmentation of
      transcriptional activity. This finding is in accordance with our observations
      that IGF-I did not influence cytokine secretion and phosphorylation of ERK in
      LNCaP or PC-3 cells. It remains to be established whether IL-8 mediates certain
      effects of IGF-I on prostate cancer cells and whether differential responsiveness
      of prostate cancer cells to IGF-I relates to certain stages of prostate cancer.

PMID- 17513151
TI  - The origin of halitosis in cystinotic patients due to cysteamine treatment.
AB  - INTRODUCTION: Cystinosis is a rare autosomal recessive disorder characterized by
      the intralysosomal accumulation of cystine. Cysteamine removes cystine from the
      lysosome and slows down the progression of the disease. One of its side effects
      is the induction of halitosis, which can interfere with patients' willingness to
      comply with cysteamine treatment. OBJECTIVE: To identify breath sulphur compounds
      causing halitosis induced by cysteamine therapy in patients with cystinosis.
      STUDY DESIGN: After the ingestion of 15mg/kg cysteamine whole blood (n=4), urine
      (n=4) and breath (n=8) volatile sulphur compounds levels were measured every
      60min over a 360min period by gas chromatography and the cysteamine plasma
      concentrations (n=4) were measured by high-performance liquid chromatography.
      RESULTS: The expired air of cystinotic patients contained elevated concentrations
      of methanethiol (MT, median maximum value 0.5 (range 0-11)nmol/L) and, in
      particular, dimethylsulphide (DMS, median maximum value 15 (range 2-83)nmol/L).
      DMS concentrations higher than 0.65nmol/L are known to cause halitosis. Maximal
      plasma values of cysteamine (median 46 (range 30-52)micromol/L) preceded those of
      MT and DMS, confirming that cysteamine is converted to MT and DMS. Less than 3%
      of the amount of cysteamine ingested was excreted as MT and DMS via expired air
      and 0.002% via urine. CONCLUSION: Halitosis induced by cysteamine intake is
      caused by DMS and to a lesser extent by MT, excreted via the expired air. Further
      studies should focus on the possibilities of reducing the formation of these
      volatile sulphur compounds or masking their odour, which would improve the rates
      of compliance with cysteamine treatment.

PMID- 17513152
TI  - Prevalence of cryptosporidian infection in cats in Turin and analysis of risk
      factors.
AB  - An epidemiological study was carried out to identify factors associated with the
      risk of cryptosporidian infection in cats. Faecal samples from 200 domestic cats
      were collected in the small animal clinic at the Faculty of Veterinary Medicine
      in Turin (north-west Italy). The faecal samples were analysed for the presence of
      Cryptosporidium species oocysts using a centrifugation concentration floatation
      method. For each cat, age, sex, breed, indoor/outdoor status, diet, diarrhoea and
      presence of other enteric parasites were analysed for association with
      Cryptosporidium species infection. Cryptosporidia oocysts were identified in 49
      cats (24.5%) aged from 2 months to 18 years. Statistical analysis revealed that
      four variables are significantly associated with an increased risk of infection:
      less than 1 year of age (chi(2)=6.5, P=0.01), feeding home-cooked diet
      (chi(2)=6.92, P<0.01), presence of diarrhoea (chi(2)=4.34, P<0.037), and presence
      of other enteric parasites (chi(2)=10.31, P<0.01). No statistical differences
      were found for sex (chi(2)=1.56, P=0.21), breed (chi(2)=0.78, P=0.38) and
      outdoor/indoor status (chi(2)=1.49, P=0.22). Cryptosporidium species was the
      parasite most frequently detected in the cats surveyed.

PMID- 17513153
TI  - Laparoscopic ovariectomy in cats: comparison of laser and bipolar
      electrocoagulation.
AB  - Fourteen mixed-breed domestic cats underwent laparoscopic ovariectomy (lapOVE)
      using paediatric equipment, an Nd:YAG laser and a bipolar electrocoagulation
      forceps. Cats were placed in 10 degrees Trendelenburg position (head down) and
      insufflation pressure was kept at 4mmHg, while surgery was performed through
      three midline portals. Randomly-assigned unilateral laser resection of one ovary
      (laserOVE) and bipolar electrocoagulation (BECOVE) of the contralateral ovary
      were performed. Duration of predetermined surgery intervals was recorded, as well
      as occurrence of intra- and postoperative complications. Both methods were
      successful and without complications. Duration of laserOVE was significantly
      increased compared to BECOVE. The right ovary was more difficult to access;
      however, both ovaries were easy to manipulate because of the relatively long
      suspensory ligament. The ovarian ligaments contained minimal amounts of fat and
      obesity did not influence surgery duration. Convalescence period was short (0.9+/
      0.4 days) and owner satisfaction high.

PMID- 17513154
TI  - Risk factors for nosocomial imipenem-resistant Acinetobacter baumannii
      infections.
AB  - OBJECTIVES: To identify the risk factors for nosocomial imipenem-resistant
      Acinetobacter baumannii (IRAB) infections. METHODS: A prospective case-control
      study, set in an 1100-bed referral and tertiary-care hospital, of all patients
      who had nosocomial A. baumannii infections between January 1 and December 31,
      2004. Only the first isolation of A. baumannii was considered. RESULTS: IRAB was
      isolated from 66 (53.7%) patients and imipenem-sensitive Acinetobacter baumannii
      (ISAB) was isolated from 57 (46.3%) patients during the study period. The mean
      duration of hospital stay until A. baumannii isolation was 20.8+/-13.6 days in
      IRAB infections, whereas it was 15.4+/-9.4 days in ISAB infections. Of the
      patients, 65.2% with IRAB infections and 40.4% with ISAB infections were followed
      at the intensive care unit (ICU). Previous carbapenem use was present in 43.9% of
      the patients with IRAB and 12.3% of the patients with ISAB infection. In
      univariate analysis female sex, longer duration of hospital stay until infection,
      ICU stay, emergent surgical operation, total parenteral nutrition, having a
      central venous catheter, endotracheal tube, urinary catheter or nasogastric tube,
      previous antibiotic use, and previous administration of carbapenems were
      significant risk factors for IRAB infections (p<0.05). In multivariate analysis,
      longer duration of hospital stay until A. baumannii isolation (odds ratio (OR)
      1.043; 95% confidence interval (CI) 1.003-1.084; p=0.032), previous antibiotic
      use (OR 5.051; 95% CI 1.004-25.396; p=0.049), and ICU stay (OR 3.100; 95% CI
      1.398-6.873; p=0.005) were independently associated with imipenem resistance.
      CONCLUSIONS: Our results suggest that the nosocomial occurrence of IRAB is
      strongly related to an ICU stay and duration of hospital stay, and that IRAB
      occurrence may be favored by the selection pressure of previously used
      antibiotics.

PMID- 17513155
TI  - [The hopes of the mesenchymal stem cells in regenerative medicine].
AB  - The mesenchymal stem cells are a cell population of bone marrow, which have the
      capacity to differentiate towards all the cells from the locomotor apparatus.
      They also have immunomodulatory properties and can contribute to tissue repair,
      thanks to the secretion of many growth factors. Such cells are also found in the
      cord blood. In the same way, very close stem cells exist in great quantity in fat
      tissue. These cells are very good candidates in regenerative medicine. Besides,
      several clinical trials were carried out in order to highlight their
      effectiveness mainly in osseous repair and also during hematopoietic stem cells
      graft or cardiac repair after infarction. However, these trials will be able to
      develop fully only with the condition that culture techniques meeting the
      conditions of good manufacturing practice are set-up. This presentation gives a
      progress report on the whole of these subjects.

PMID- 17513156
TI  - [The supply chain is everybody's business...].
AB  - The management of the supply chain is a matter of delicate balance. This is
      certainly due to its position at the crossroads between suppliers and users
      requirements, as well as logistic, financial and technical regulations. For a
      public organisation like EFS, whose annual budget amounts to 697 million euros,
      there is a lot at stake: supplies represent the second most important item of its
      budget accounting for 38% of annual expenses. Three quarters of the purchases
      concern basic activities such as blood collection, testing procedures,
      transformation and distribution of blood products. The last quarter is spent on
      more general activities (computer systems, telecommunications...).
      Professionalisation of the purchasing function has grown since the creation of
      the government-owned organisation as a single national unit (EFS) in the year
      2000. Its consequences can be felt especially in the field of the "core
      activities". The current stage consists in maintaining close links between all
      the skills necessary to a high-quality supply chain. The latter will undoubtedly
      be beneficial to the medical, technical and support departments of EFS, which are
      the in-house customers to satisfy.

PMID- 17513157
TI  - [Factors affecting posttransfusion platelet efficiency "close relationship
      between patient and product"].
AB  - A great variety of patient- and product-related factors influence the outcome of
      platelet transfusions. The patient-related factors are numerous, either physical
      factors as weight and height, or related to pathological being as splenomegaly,
      fever, infection, disseminated intravascular coagulation, previous HLA allo
      immunization, or related to the treatment, as amphotericin. Major platelet
      factors that are associated with impaired responses are giving a decreased dose
      of platelets, ABO incompatible products, and platelets stored for more than 48
      hours. When trying to prevent or to treat refractoriness and to finely tune
      platelet transfusions, all these factors have to be taken into account, and a
      good coordination between the blood bank and the clinician team is essential.

PMID- 17513158
TI  - [Haemovigilance donors: methods and results].
AB  - There is no official definition of haemovigilance donors. However, it concerns
      the observation and management of Serious Adverse Events observed in blood donors
      (SAEDs), Post Donation Informations (PDI), and donor epidemiologic survey. The
      French Decree of 1 February 2006 imposes the declaration of the SAEDs. In 2006,
      196 SAEDs were notified for 2599978 donations (7.5/100,000 donations). The
      incidence of the SAEDs was of 7/100,000 whole blood donations and 10.7/100,000
      aphaeresis donations. Donors that are more susceptible to present a SAED are:
      women, women under 30, repeat donor and aphaeresis donor. For 2/3 of donors
      having presented a SAED, a medical consultation was prescribed and 1/3 was
      hospitalized. Vasovagal reaction is the most frequent category. Seven thousand
      three hundred and sixty one PDI were notified in 2005. The risks of infection
      represented the principal cause (mainly ENT). Concerning donor epidemiologic
      survey, the viral residual risk clearly decreased since 1992 and for the period
      of 2003-2005 it 1/2600000 for HIV, 1/6500000 for HCV and 1/1000000 for HBV. The
      first national data already give useful information. This information will permit
      a better care of blood donors and of blood component recipients as well.

PMID- 17513159
TI  - [Transfusion safety and haemovigilance committees].
AB  - Transfusion safety and haemovigilance committees (TSHC) were initially created in
      the public health care sector. Nowadays, they are also a mandatory committee of
      private health care institutions. The members of the TSHC, as well as the way the
      committee is driven and organized, are defined by law. The aim of the committee
      is focused on the management of transfusion safety and haemovigilance. The TSHC
      takes part in the improvement of the safety of transfused patients, and monitors
      the applying of haemovigilance rules. It also handles the training of all staff
      members involved in the blood transfusion process.

PMID- 17513160
TI  - [What determines the sick leave of repair and rehabilitation of the hand flexor
      tendons injuries].
AB  - OBJECTIVES: The purpose of this study is to analyse the relationship between the
      social and economical consequences, after repair and rehabilitation of the hand
      flexor tendon injuries, and to prove that it is not related to local factors.
      METHOD: All the patients who underwent surgery for at least one flexor tendons
      injury of one or several long fingers, between the years 2003-2004 were included
      in this study. Information regarding the data was taken from the patient file.
      Statistical tests were used for analysing these data. RESULTS: Significant first
      rate factors related to the length of sick leave are the chaotic professional
      history (P=0.03), the type of occupation (P=0.01) and the age (P=0.0002). A
      significant second rate factor is represented by the type of
      mobilization/retraining (P=0.04). Sex, side of injury, finger injured, zone of
      injury, associated damages, did not significantly influence the results of this
      study. CONCLUSION: The environmental factors determine the length of sick leave
      more than the characteristic of injury in hand flexor tendons surgery.

PMID- 17513161
TI  - [Partial trapezectomy with suspension and interposition tendinoplasty for
      trapezometacarpal osteoarthritis: 5 years results].
AB  - OBJECTIVES: Partial trapezectomy with suspension and interposition tendinoplasty
      is an alternative to total trapezectomy or trapezometacarpal arthroplasty for the
      treatment of trapezometacarpal osteoarthritis. This technique preserves the thumb
      length allowing good motion and satisfactory pollicidigital strength. The purpose
      of the present study is to report our experience with this procedure reviewing a
      continuous monocentric series of 41 thumbs with an averaged follow-up of 5 years.
      Surgical technique, clinical and radiographic results, and indications are
      discussed. METHODS: Thirty-three patients (41 thumbs) of 57.4 years average age
      underwent this procedure. According to Dell classification there were 23 stage
      II, 15 stage III, and 3 stage IV. No sign of osteoarthritis of the scapho-trapezo
      trapezoidal joint were noted. Clinical and radiographic evaluations were
      available for all the patients. Pollicidigital strength was measured with a
      dynamometer. RESULTS: At 57 months average follow-up, 71% of the patients had no
      pain. Average opposition was 9.56 out of 10 according to Kapandji, the key pinch
      was equal to 6.51 kg, and M1M2 space was 34 degrees . Trapezometacarpal space was
      2.52 mm on average. There were only 3 complications related to a reflex
      sympathetic dystrophy. CONCLUSION: Partial trapezectomy with tendinoplasty gives
      satisfactory functional results which is maintained with follow-up. It allows
      recovery of a functional pollicidigital strength by limiting thumb shortening. It
      is a reliable procedure with a low rate of complication indicated for isolated
      thumb trapezometacarpal joint osteoarthritis without scapho-trapezo-trapezoidal
      joint involvement.

PMID- 17513162
TI  - [Five questions about the Kiwi OmniCup vacuum extractor].
AB  - The vacuum extractor Kiwi OmniCup (Clinical Innovations, Muray, Utah, USA) has
      been developed to provide several advantages. This is a complete system with an
      integral hand-held vacuum operated by the obstetrician. This is also a single use
      instrument, which may reduce the risk of potential transmission of infections and
      the logistic of sterilization process. Further potential benefits of this system
      include the smaller overall equipment size and the ability to measure traction
      force. However, the data about its efficiency remain conflicting. The first works
      demonstrated very high successful rate of vaginal delivery, whereas two recent
      randomized studies showed that the Kiwi Omnicup was less efficient than currently
      used vacuum extractor. It appears to be as safe as conventional a device for both
      mother and newborn. However, further additional data remain necessary needed to
      complete its evaluation.

PMID- 17513163
TI  - A modified elastic foundation contact model for application in 3D models of the
      prosthetic knee.
AB  - Different models have been used in the literature for the simulation of surface
      contact in biomechanical knee models. However, there is a lack of systematic
      comparisons of these models applied to the simulation of a common case, which
      will provide relevant information about their accuracy and suitability for
      application in models of the implanted knee. In this work a comparison of the
      Hertz model (HM), the elastic foundation model (EFM) and the finite element model
      (FEM) for the simulation of the elastic contact in a 3D model of the prosthetic
      knee is presented. From the results of this comparison it is found that although
      the nature of the EFM offers advantages when compared with that of the HM for its
      application to realistic prosthetic surfaces, and when compared with the FEM in
      CPU time, its predictions can differ from FEM in some circumstances. These
      differences are considerable if the comparison is performed for prescribed
      displacements, although they are less important for prescribed loads. To solve
      these problems a new modified elastic foundation model (mEFM) is proposed that
      maintains basically the simplicity of the original model while producing much
      more accurate results. In this paper it is shown that this new mEFM calculates
      pressure distribution and contact area with accuracy and short computation times
      for toroidal contacting surfaces. Although further work is needed to confirm its
      validity for more complex geometries the mEFM is envisaged as a good option for
      application in 3D knee models to predict prosthetic knee performance.

PMID- 17513165
TI  - A computational model of activities performance decrease in Alzheimer's disease.
AB  - This article presents a computational model and a simulation of the decrease of
      performance in daily living activities due to Alzheimer's disease. The framework
      offered by the cognitive architecture ACT-R is used to develop the model. Typical
      errors committed in performing tasks by Alzheimer patients are modelled thanks to
      different parametrisable memory mechanisms of ACT-R and the disease evolution is
      represented by the increase of errors in the execution of the task. The model is
      applied to a cooking activity. Simulation of 100 subjects shows results similar
      to those realised in a standardized assessment with human subjects. We conclude
      on the need to introduce executive mechanisms in the modelling of behaviours
      associated to people with cognitive deficits.

PMID- 17513164
TI  - A long and winding road: the Plasmodium sporozoite's journey in the mammalian
      host.
AB  - The Plasmodium sporozoite, the infectious stage of the malaria parasite, makes a
      remarkable journey in its mammalian host. Here we review our current knowledge of
      the molecular and cellular basis of this journey, which begins in the skin and
      ends in the hepatocyte.

PMID- 17513166
TI  - Towards automated classification of intensive care nursing narratives.
AB  - BACKGROUND: Nursing narratives are an important part of patient documentation,
      but the possibilities to utilize them in the direct care process are limited due
      to the lack of proper tools. One solution to facilitate the utilization of
      narrative data could be to classify them according to their content. OBJECTIVES:
      Our objective is to address two issues related to designing an automated
      classifier: domain experts' agreement on the content of classes Breathing, Blood
      Circulation and Pain, as well as the ability of a machine-learning-based
      classifier to learn the classification patterns of the nurses. METHODS: The data
      we used were a set of Finnish intensive care nursing narratives, and we used the
      regularized least-squares (RLS) algorithm for the automatic classification. The
      agreement of the nurses was assessed by using Cohen's kappa, and the performance
      of the algorithm was measured using area under ROC curve (AUC). RESULTS: On
      average, the values of kappa were around 0.8. The agreement was highest in the
      class Blood Circulation, and lowest in the class Breathing. The RLS algorithm was
      able to learn the classification patterns of the three nurses on an acceptable
      level; the values of AUC were generally around 0.85. CONCLUSIONS: Our results
      indicate that the free text in nursing documentation can be automatically
      classified and this can offer a way to develop electronic patient records.

PMID- 17513167
TI  - Effect of imiquimod in anogenital warts from HIV-positive men.
AB  - BACKGROUND: HIV-positive patients have unpredictable local immune responses even
      with severe systemic immunosuppression and data reported to date is insufficient
      to predict the effect of imiquimod in HIV-positive patients. OBJECTIVE: To
      evaluate the efficacy of 5% topical imiquimod in HIV-positive male patients with
      anogenital warts (AGW) and to elucidate its effect on recurrence. STUDY DESIGN:
      Open-label clinical trial. RESULTS: Of the 43 patients enrolled, 86% completed
      treatment. Patients' mean age was 34 years (range: 19-50). Thirty-one patients
      were receiving highly active antiretroviral therapy (HAART) therapy. At week 16,
      10 patients completely cleared lesions and 21 patients had a wart size reduction
      > or =50%. At 20 weeks of therapy, 17 patients achieved total clearance whereas
      14 patients had a >50% wart reduction. Clearance was not influenced by CD4
      counts, HIV-viral load, previous therapy, or wart localization. Of the patients
      who experienced a complete clearance, five (29%) had a recurrence. Mean time of
      recurrence was 14.4 weeks. Erythema, pruritus, and burning sensation were the
      most frequent local skin reactions. CONCLUSIONS: Topical 5% imiquimod is safe and
      may benefit HIV-positive patients with anogenital warts particularly when it is
      used for up to 20 weeks. It is also useful to decrease wart recurrence.

PMID- 17513168
TI  - A role for high density lipoproteins in hepatic phosphatidylcholine homeostasis.
AB  - Choline is (95%) found largely in the biosphere as a component of
      phosphatidylcholine (PC) which is made from choline via the CDP-choline pathway.
      Animals obtain choline from both the diet and via endogenous biosynthesis that
      involves the conversion of phosphatidylethanolamine into PC by
      phosphatidylethanolamine N-methyltransferase (PEMT), followed by PC catabolism.
      We have uncovered a striking gender-specific conservation of choline in female
      mice that does not occur in male mice. Female Pemt(-/-) mice maintained hepatic
      PC/total choline levels during the first day of choline deprivation and escaped
      liver damage whereas male Pemt(-/-) mice did not. Plasma PC levels in high
      density lipoproteins (HDLs) were higher in male Pemt(-/-) mice than those in
      females before choline deprivation. Interestingly, after choline deprivation for
      1 day, female, but not male, Pemt(-/-) mice increased HDL-PC levels.
      Glybenclamide, an inhibitor of PC efflux mediated by ABC transporters, eliminated
      this response to choline deprivation in females. These data suggest that (i)
      increased PC efflux from extra-hepatic tissues to HDLs in the circulation
      provided sufficient choline for the liver and compensated for loss of hepatic PC
      during the initial stages of choline deprivation in female, but not male, Pemt(-/
      ) mice, and (ii) plasma HDL in female mice has an important function in
      maintenance of hepatic PC as an acute response to severe choline deprivation.

PMID- 17513169
TI  - Smoking interacts with sleep apnea to increase cardiovascular risk.
AB  - BACKGROUND: Sleep apnea syndrome is an important risk factor for atherosclerosis
      and cardiovascular morbidity and so is cigarette smoking. In both atherosclerosis
      and cardiovascular disease, oxidative stress and inflammation have been
      implicated as underlying pathophysiologic mechanisms. We investigated oxidative
      stress and inflammatory markers in 70 non-smoking and smoking patients with sleep
      apnea. METHODS: Thirty-five sleep apnea patients aged 20-60 years who smoke 20 or
      more cigarettes/day and for at least 5 years were individually matched by gender,
      age (+/-5 years), body mass index (BMI; categorized as, 'normal weight',
      'overweight', and 'obese'), sleep apnea severity (categorized as 'mild',
      'moderate', and 'severe'), and presence of cardiovascular diseases, with 35
      patients who never smoked. Blood samples were drawn after an overnight fasting
      for determination of lipids profile, oxidative stress markers thiobarbituric acid
      reactive substances, peroxides and paraoxonase-1 and inflammatory markers C
      reactive protein, ceruloplasmin, and haptoglobin. RESULTS: Smokers showed
      significantly higher levels of C-reactive protein, ceruloplasmin, and haptoglobin
      and triglycerides and lower levels of high-density lipoprotein (HDL) cholesterol
      than non-smokers. There was a significant interaction effect between smoking and
      apnea severity on ceruloplasmin and HDL levels. Smokers with severe sleep apnea
      had the highest level of ceruloplasmin and the lowest level of HDL. CONCLUSION:
      There is a synergistic effect between cigarette smoking and sleep apnea on some
      of the biochemical cardiovascular risk markers. Patients with severe sleep apnea
      who smoke are at a greater cardiovascular risk than smokers with mild-moderate
      sleep apnea and patients who do not smoke.

PMID- 17513171
TI  - Effects of obstructive sleep apnea on cognitive function: a comparison between
      younger and older OSAS patients.
AB  - BACKGROUND AND PURPOSE: Patients with obstructive sleep apnea syndrome (OSAS)
      present cognitive deficits similar to those observed with aging. The aim of the
      study was to assess the effects of age on cognitive functions in OSAS patients.
      It was hypothesized that older OSAS patients will exhibit significant cognitive
      dysfunction relative to younger OSAS patients and controls. PATIENTS AND METHODS:
      Younger and older OSAS patients were compared to younger and older control
      subjects (age cut-off set at 50 yrs). Participants underwent a polysomnographic
      (PSG) and neuropsychological evaluation. Variables were analyzed by two-way
      analyses of variance (ANOVAs) with two factors: Group (control and OSAS) and Age
      (younger and older). Additionally, we evaluated the contribution of attentional
      deficits to cognitive dysfunction for each subgroup of patients by using Spearman
      correlation coefficients. RESULTS: No Group-by-Age interaction was found for any
      neuropsychological variables (p<0.05). However, main Group and Age effects were
      found. Correlations indicated that attentional deficits contributed importantly
      to a poorer cognitive performance in younger OSAS patients only (p<0.01).
      CONCLUSIONS: Our results are in agreement with those of the literature for both
      OSAS-related and aging-related cognitive deficits but did not demonstrate that
      age interacts with the effects of the OSAS condition to make those cognitive
      deficits worse.

PMID- 17513172
TI  - Microvessel density as a prognostic factor in non-small-cell lung carcinoma: a
      meta-analysis of individual patient data.
AB  - BACKGROUND: Angiogenesis is a potential prognostic factor that has been
      investigated in patients with non-small-cell lung carcinoma. However, published
      studies of the role of angiogenesis as a prognostic factor are inconclusive. We
      aimed to collect individual patient data to assess microvessel-density counts
      (ie, a measure of angiogenesis) as a prognostic factor in non-small-cell lung
      carcinoma. METHODS: We obtained published and unpublished datasets and extracted
      appropriate data, taking particular care to ensure data quality. Detailed
      information was obtained for the laboratory methods used by every research centre
      that generated the data. The outcome of interest was overall survival. We did a
      meta-analysis to estimate the prognostic role of microvessel density by combining
      separately estimated hazard ratios (HR) from every study, which were adjusted for
      tumour stage and age. Analyses were done separately for studies that used the
      Chalkley method or for those that counted all microvessels. FINDINGS: 17 centres
      provided data for 3200 patients, 2719 of which were included in the analysis. All
      but three centres (datasets 9, 10, and 13-367 cases) had already published their
      findings, and six had updated follow-up information (datasets 1, 2, 3, 6, 7, and
      8-1273 cases). For all but three centres (datasets 4, 11, and 13) some data
      corrections were necessary. For microvessel density counts obtained by the
      Chalkley method, the HR for death per extra microvessel was 1.05 (95% CI 1.01
      1.09, p=0.03) when analysed as a continuous variable. For microvessel density
      counts obtained by the all vessels method, the HR for death per ten extra
      microvessels was 1.03 (0.97-1.09, p=0.3) when analysed as a continuous variable.
      INTERPRETATION: Microvessel density does not seem to be a prognostic factor in
      patients with non-metastatic surgically treated non-small-cell lung carcinoma.
      This conclusion contradicts the results of a meta-analysis of published data
      only. Therefore, the methodology used to assess prognostic factors should be
      assessed carefully.

PMID- 17513174
TI  - Association of polymorphisms in the first exon of mannose binding lectin gene
      (MBL2) in Brazilian patients with HCV infection.
AB  - In our study we investigated the role of the polymorphisms in the first exon of
      MBL2 gene in the susceptibility to HCV infection and disease progression in a
      Northeastern Brazilian population. One hundred and eleven patients seen at the
      Gastroenterology Service of the Oswaldo Cruz Hospital of the University of
      Pernambuco were included in this study. A total of 165 unexposed, uninfected
      individuals matched for place of origin were employed as healthy controls. MBL2
      genotyping was performed by using a melting temperature assay. The 0 allele was
      significantly more frequent in the HCV positive group than the healthy controls
      (34% vs. 20%, p<0.01, respectively) and was associated to an increased risk of
      HCV-1 infection (O.R.=2.1; C.I. 1.41-3.19). Also genotypes frequencies were
      significantly different in HCV positive subjects when compared to healthy
      controls with the 00 and A0 genotypes being significantly overrepresented in HCV
      infected subject (15% and 37%, respectively) as compared to healthy subjects (6%
      and 27%, respectively, p<0.01 ) Allele and genotypes frequencies were also
      evaluated in HCV infected subjects according to their response to pegylated
      INFalpha/riboviron therapy. There was a trend for HCV positive responders vs. non
      responders to be 0 allele positive and a similar trend was observed for the MBL2
      A0 and 00 genotypes, but neither of these reached statistical significance. Our
      findings indicate that MBL might represent an important antiviral molecule having
      a protective role in the first stages of HCV infection, as shown by the increased
      frequency of wild-type alleles in control population as compared to the infected
      group.

PMID- 17513173
TI  - Factorial phase III randomised trial of rofecoxib and prolonged constant infusion
      of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in
      NSCLC (GECO) study.
AB  - BACKGROUND: The addition of cyclo-oxygenase-2 (COX-2) inhibitors and prolonged
      constant infusion (PCI) of gemcitabine to treatment for advanced non-small-cell
      lung cancer (NSCLC) might improve treatment efficacy. We aimed to assess whether
      the addition of rofecoxib or PCI gemcitabine could improve overall survival
      compared with first-line treatment with cisplatin plus gemcitabine given by
      standard infusion. METHODS: Patients with stage IV or IIIb (with supraclavicular
      nodes or pleural effusion) NSCLC who were under 70 years of age and who had
      performance status 0 or 1 were eligible for this multicentre, prospective, open
      label, randomised phase III trial with 2 x 2 factorial design. Patients were
      randomly assigned to one of four treatment groups: group A, gemcitabine 1200
      mg/m(2) in a 30-min intravenous infusion on days 1 and 8 and intravenous
      cisplatin 80 mg/m(2) on day 1, every 21 days for six cycles; group B, the same
      treatments as group A plus oral rofecoxib 50 mg/day until disease progression;
      group C, intravenous PCI gemcitabine 1200 mg/m(2) in a 120-min infusion on days 1
      and 8 and intravenous cisplatin 80 mg/m(2) on day 1, every 21 days for six
      cycles; group D, the same drugs as group C plus oral rofecoxib 50 mg/day until
      disease progression. The primary endpoint was overall survival; secondary
      endpoints were progression-free survival, response rate, quality of life, and
      toxicity. Analyses were intention-to-treat. This trial is registered on the
      clinical trials site of the US National Institutes of Health website
      http://clinicaltrials.gov/ct/show/NCT00385606. FINDINGS: Between Jan 30, 2003,
      and May 3, 2005, 400 patients were enrolled. Median age was 60 years (range 29
      71). PCI gemcitabine did not improve overall survival (median 47 weeks [95% CI 40
      55] vs 44 [36-52], with standard gemcitabine infusion, hazard ratio (HR) of death
      0.93 [0.74-1.17], p=0.41), progression-free survival, nor any other secondary
      endpoint. Vomiting and fatigue were significantly worse with PCI gemcitabine. The
      two rofecoxib groups were closed early (on Oct 1, 2004) due to withdrawal of the
      drug because of safety issues. With intention-to-treat statistical analyses
      limited to 240 patients (ie, those randomised before July 1, 2004) who had at
      least 3 months of treatment, rofecoxib did not prolong overall survival (median
      44 weeks [CI 36-55] vs 44 [40-54] without rofecoxib, and HR of death 1.00 [0.75
      1.34], p=0.85), or progression-free survival, but did improve response rate
      (41%vs 26%, p=0.02), global quality of life, physical, emotional and role
      functioning, fatigue, and sleeping. Rofecoxib significantly increased the
      incidence of diarrhoea and decreased constipation, fatigue, fever, weight loss,
      and pain, and analgesic consumption. Severe cardiac ischaemia was more frequent
      with rofecoxib than without; however, the difference was not statistically
      significant in the primary analysis (p=0.06) and became significant when patients
      who were randomised between July 1, 2004, and Sept 30, 2004, were included in the
      analysis (p=0.03). INTERPRETATION: Neither PCI gemcitabine nor rofecoxib
      prolonged survival in the patients in this study. Rofecoxib improved response
      rate and several quality-of-life items, including pain-related items and global
      quality of life. Further studies with less cardiotoxic COX-2 inhibitors are
      needed in NSCLC.

PMID- 17513175
TI  - Acute rejection of experimental lung allografts: characterization of
      intravascular mononuclear leukocytes.
AB  - Leukocytes interacting with endothelia of lung allografts probably play a seminal
      role in acute rejection, but have not been characterized before. Transplantation
      was performed in the Lewis to Lewis and in the Dark Agouti to Lewis rat strain
      combinations. DNA replication was detected in T-cells on day 2 after pulse
      labelling in vivo with 5-bromo-2'-deoxyuridine (BrdU). On day 5, leukocytes were
      isolated by intensive perfusion the graft, subject to flow cytometry and to
      quantitative RT-PCR. About 34 million leukocytes accumulated in allograft
      vessels, but only 10 and 6 million cells in isografts and control lungs,
      respectively. During rejection, IFN-gamma, IL-1beta and IL-10 mRNA expression
      increased, IL-12 mRNA decreased, whereas IL-2, IL-6, TNF-alpha, and TGF-beta mRNA
      did not change. The phenotype of graft monocytes was partially activated and
      intravascular T-cells proliferated. In conclusion, during rejection, monocytes
      with unusual properties accumulate and T-lymphocytes are activated in lung
      allograft blood vessels.

PMID- 17513176
TI  - C1q deficiency in an Inuit family: identification of a new class of C1q disease
      causing mutations.
AB  - C1q deficiency is a rare condition associated with a systemic lupus erythematosus
      (SLE)-like syndrome and recurrent infections. Here we present the molecular basis
      behind C1q deficiency in three sisters of Inuit origin. Initial examination for
      complement deficiency showed no function of the classical complement activation
      pathway in the patients; the lectin and alternative pathways were intact. No C1q
      or low molecular weight C1q was detected in sera and no anti-C1q autoantibodies
      were found. Sequencing of the C1q genes revealed a novel missense mutation (Gly
      Arg) in codon 217 of the B chain. All sisters were homozygous for the mutation:
      both parents were heterozygous. None of 100 healthy controls carried the
      mutation. Our findings define a third class of molecular mechanisms behind C1q
      deficiency, where missense mutations cause a lack of detectable C1q-antigen in
      serum.

PMID- 17513178
TI  - Vagus nerve stimulation in children with mitochondrial electron transport chain
      deficiencies.
AB  - We retrospectively investigated outcome data for vagus nerve stimulation (VNS) in
      children less than 12 years of age with intractable seizures and mitochondrial
      disease. Five children with a mitochondrial disease, due to electron transport
      chain deficiency, were studied. Information was collected from clinic visits
      prior to, and subsequent to, VNS implantation. Data were collected by type and
      frequency of seizures, encephalogram and neuroimaging findings, and medication
      history. Four of the children had predominantly myoclonic seizures, while the
      other child had focal seizures with secondary generalization and myoclonic
      seizures. All five children did not have significant reduction in seizure
      frequency with VNS. VNS may not be an effective method to control myoclonic
      seizures in children with electron transport chain disorders.

PMID- 17513177
TI  - Immunofluorescence microscopy is superior to fluorescent beads for detection of
      antinuclear antibody reactivity in systemic lupus erythematosus patients.
AB  - Antinuclear antibodies (ANA) are a hallmark of systemic lupus erythematosus (SLE)
      and one of its key diagnostic criteria. Recently, new technologies based on
      antibody binding to fluorescence beads (FB) have been widely employed for ANA
      screening. We conducted a formal study in 385 consecutive patients who underwent
      both traditional immunofluorescence (IF) and FB testing and evaluated each
      patient for the diagnosis of SLE. The distribution of ANA test results was
      significantly different (chi(2)=73.12; p<0.0001) due to a marked discordance of
      double-negative and double-positive results. The concordance of the FB-negative
      and IF-negative test results was 240/256 (95.6%), while the concordance of double
      positive results was 54/129 (41.9%). The sensitivity of IF was markedly higher
      (48/53; 90.6%) than that of the FB (26/53; 49.1%; p<0.0001) for the diagnosis of
      SLE. IF had a lower specificity (76%) than FB (87%; p=0.0002). The present data
      show that the IF assay has superior sensitivity for detection of ANA and should
      continue to be used as the primary screening test for the diagnosis of SLE.

PMID- 17513179
TI  - The Mass Distance Fingerprint: a statistical framework for de novo detection of
      predominant modifications using high-accuracy mass spectrometry.
AB  - We describe a statistical measure, Mass Distance Fingerprint, for automatic de
      novo detection of predominant peptide mass distances, i.e., putative protein
      modifications. The method's focus is to globally detect mass differences, not to
      assign peptide sequences or modifications to individual spectra. The Mass
      Distance Fingerprint is calculated from high accuracy measured peptide masses.
      For the data sets used in this study, known mass differences are detected at
      electron mass accuracy or better. The proposed method is novel because it works
      independently of protein sequence databases and without any prior knowledge about
      modifications. Both modified and unmodified peptides have to be present in the
      sample to be detected. The method can be used for automated detection of
      chemical/post-translational modifications, quality control of experiments and
      labeling approaches, and to control the modification settings of protein
      identification tools. The algorithm is implemented as a web application and is
      distributed as open source software.

PMID- 17513180
TI  - Pseudomonas aeruginosa contains multiple glyoxalase I-encoding genes from both
      metal activation classes.
AB  - The glyoxalase (Glx) system is a critical detoxification enzyme system that is
      widely distributed in prokaryotic and eukaryotic organisms. Glyoxalase I (GlxI),
      the first enzyme in the system, is a divalent metal-ion dependent lyase
      (isomerizing), and its homologs have recently been categorized into two metal
      activation classes which are either Zn2+-dependent or non-Zn2+ dependent (Ni2+
      /Co2+-activated). The latter class encompasses enzymes of predominantly bacterial
      origin. We have identified two genes in Pseudomonas aeruginosa PAO1 encoding
      glyoxalase I enzymes in addition to the gloA1 sequence recently reported and
      characterized. The gloA1 and gloA2 genes encode non-Zn2+ dependent glyoxalase I
      enzymes and the gloA3 gene remarkably encodes a Zn2+-dependent homolog. To our
      knowledge this is the first report of a eubacterial species with several GlxI
      encoding genes, and also of an organism possessing GlxI enzymes from both metal
      activation classes.

PMID- 17513182
TI  - Pedunculated giant GISTs of the stomach with exophytic growth: report of two
      cases.

PMID- 17513181
TI  - Incremental changes in anisotropy induce incremental changes in the material
      properties of electrospun scaffolds.
AB  - Electrospinning can be used to selectively process a variety of natural and
      synthetic polymers into highly porous scaffolds composed of nano-to-m diameter
      fibers. This process shows great potential as a gateway to the development of
      physiologically relevant tissue engineering scaffolds. In this study, we examine
      how incremental changes in fiber alignment modulate the material properties of a
      model scaffold. We prepared electrospun scaffolds of gelatin composed of varying
      fiber diameters and degrees of anisotropy. The scaffolds were cut into a series
      of "dog-bone" shaped samples in the longitudinal, perpendicular and transverse
      orientations and the relative degree of fiber alignment, as measured by the fast
      Fourier transform (FFT) method, was determined for each sample. We measured peak
      stress, peak strain and the modulus of elasticity as a function of fiber diameter
      and scaffold anisotropy. Fiber alignment was the variable most closely associated
      with the regulation of peak stress, peak strain and modulus of elasticity.
      Incremental changes, as judged by the FFT method, in the proportion of fibers
      that were aligned along a specific axis induced incremental changes in peak
      stress in the model scaffolds. These results underscore the critical role that
      scaffold anisotropy plays in establishing the material properties of an
      electrospun tissue engineering scaffold and the native extracellular matrix.

PMID- 17513183
TI  - Emergency department thoracotomy in Jamaica: a case controlled study.
AB  - Increasing numbers of severely injured patients have been presenting to Emergency
      Rooms worldwide due to advances in pre-hospital trauma care. Some of these
      patients may be candidates for Emergency Department Thoracotomy (EDT). Large
      advisory bodies have identified selection criteria for EDT in Developed
      Countries, but there are no regional statistics to guide the selection process in
      Developing Caribbean Nations. This study evaluates outcomes with EDT at the
      University Hospital of the West Indies in Jamaica in order to determine factors
      that could predict survival in this setting. A retrospective study was performed
      over 11 years from January 1995 to January 2006 examining patients who had EDT at
      the University Hospital of the West Indies. There were 13 procedures performed
      over 11 years, with two early survivors (15%) and one patient surviving to
      discharge. The factors that have been found to be significant predictors of
      mortality include gunshot injuries, extra-thoracic injury location, inadequate
      pre-hospital resuscitation, prolonged transportation time and the absence of
      signs of life on arrival to hospital. Several health care limitations have been
      uncovered in this setting that must be improved if we are to expect improved
      outcomes. Focused preparation of the Emergency Room is an initial step that can
      be easily achieved. We also need to define strict management protocols using
      selection criteria that are tailored to our local environment in order to exclude
      futile procedures in unsalvageable patients.

PMID- 17513184
TI  - Antenatal magnesium sulphate neuroprotection in the preterm infant.
AB  - Very preterm infants have high rates of neurological impairments and
      disabilities. These rates have not diminished as the survival rates have
      improved. Basic science research suggests that magnesium sulphate before birth
      can be neuroprotective for the preterm fetus. Some, but not all, observational
      studies in humans also suggest a protective effect of antenatal magnesium
      sulphate on cerebral palsy. Four randomised controlled trials of antenatal
      magnesium sulphate have reported long-term neurological effects in surviving
      infants, but only one of these was designed specifically to evaluate the long
      term effects of treatment. These studies found that, overall, antenatal magnesium
      sulphate therapy had no significant effect on paediatric mortality or
      neurological outcomes in the first few years of life, including cerebral palsy,
      but it was found to lower the rate of motor problems at 2 years of age in one
      study. The role for antenatal magnesium sulphate therapy as a neuroprotective
      agent for the preterm fetus is not yet established.

PMID- 17513185
TI  - Structural trends in the aging proximal femur in Japanese postmenopausal women.
AB  - Hip structure analysis (HSA) can be used to measure proximal femur geometry using
      conventional DXA scans of the hip. This study is the first analysis of HSA data
      in Japanese women to evaluate apparent age trends in the geometry of cross
      sectional regions in the proximal femur. 409 Japanese women aged from 50 to 93
      years of age were measured by DXA at three sites (narrow neck, intertrochanter,
      shaft). Using the mean value those between 50-59 years as a reference value, age
      trends were evaluated using groupings of 5-year intervals and those over 80 as a
      single group. BMD at three measured sites and section modulus (index of bending
      strength) at narrow neck declined in a similar age dependent manner, but section
      modulus at intertrochanter and shaft showed a different pattern. The decline in
      section modulus at narrow neck occurs after 50-59 years of age, whereas section
      modulus at intertrochanter remain 70-74 years, after that began to decrease.
      Section modulus at shaft, an uncommon fracture location, remains fairly static
      through life. In conclusion, HSA in Japanese women showed that reduction in
      geometric strength, as reflected by the section modulus, was not dependent on
      decline in BMD.

PMID- 17513186
TI  - Effects of continuous activation of vitamin D and Wnt response pathways on
      osteoblastic proliferation and differentiation.
AB  - The Wnt pathway regulates cell proliferation and differentiation in development
      and disease, with a number of recent reports linking Wnt to control of osteoblast
      differentiation and bone mass. There is also accumulating evidence for
      interaction between the Wnt and nuclear receptor (NR)-mediated control pathways
      in non-osseous tissues. Calcitriol (1,25D(3)), which is the active hormonal
      ligand for the vitamin D receptor (VDR), a member of the NR superfamily, induces
      osteoblastic cell cycle arrest and expression of genes involved in matrix
      mineralization in vitro, with over-expression of VDR in mature osteoblasts
      increasing bone mass in mice. To determine whether the vitamin D and Wnt control
      pathways interact in osteoblastic regulation, we investigated the treatment
      effects of 1,25D(3) and/or lithium chloride (LiCl), which mimics canonical Wnt
      pathway activation, on osteoblast proliferation and differentiation. Treatments
      were initiated at various stages in differentiating cultures of the MC3T3-E1
      osteoprogenitor cell line. Treatment of subconfluent cultures (day 1) with either
      agent transiently increased cell proliferation but decreased viable cell number,
      with additive inhibition after combined treatment. Interestingly, although early
      response patterns of alkaline phosphatase activity to 1,25D(3) and LiCl were
      opposite, mineralized nodule formation was virtually abolished by either
      treatment initiated at day 1 and remained very low after initiating treatments at
      matrix-formation stage (day 6). By contrast, mineralized nodule formation was
      substantial but reduced if 1,25D(3) and/or LiCl treatment was initiated at
      mineralization onset (day 13). Osteocalcin production was reduced by all
      treatments at all time points. Thus, vitamin D and/or canonical Wnt pathway
      activation markedly reduced mineralization, with additive inhibitory effects on
      viable cell number. The strength of the response was dependent on the stage of
      differentiation at treatment initiation. Importantly, the inhibitory effect of
      LiCl in this committed osteoblastic cell line contrasts with the stimulatory
      effects of genetic Wnt pathway activation in human and mouse bone tissue. This is
      consistent with the anabolic Wnt response occurring at a stage prior to the
      mature osteoprogenitor in the intact skeleton and suggests that prolonged or
      repeated activation of the canonical Wnt response in committed cells may have an
      inhibitory effect on osteoblast differentiation and function.

PMID- 17513187
TI  - Accuracy of contrast-enhanced breast ultrasound for pre-operative tumor size
      assessment in patients diagnosed with invasive ductal carcinoma of the breast.
AB  - Our aim was to assess the feasibility and accuracy of contrast-enhanced
      ultrasound (CEUS) of the breast with SonoVue microbubbles for pre-operative size
      measurement of invasive breast carcinomas. Seven patients diagnosed with nine
      invasive breast carcinomas prospectively underwent gray-scale ultrasound and CEUS
      of the breast according to a standardized protocol. CEUS of the breast was
      performed by a Philips iU22 scanner equipped with a 4-8 MHz linear array
      transducer. We used a single dose of 2.4 ml SonoVue as contrast agent. Breast
      lesion morphology was scored according to the sonographic BI-RADS lexicon
      criteria and classified accordingly. The greatest tumor dimensions on gray-scale
      ultrasound and CEUS of the breast were finally compared with the greatest
      histopathologic tumor sizes. Gray-scale ultrasound underestimated the
      histopathologic tumor size in 6/9 cases (67%), whereas CEUS of the breast
      underestimated tumor size in only 3/9 (33%) cases. CEUS of the breast was
      significantly more accurate for tumor size assessment. Greatest tumor dimension
      as measured with gray-scale ultrasound of the breast was within 2 mm of the
      pathologic tumor size in only 2/9 cases (22%), whereas CEUS of the breast
      accurately assessed tumor size within 2 mm of pathologic tumor size in 6/9 (67%)
      of the cases (P<0.05). CEUS of the breast proved to be a feasible and safe
      procedure. It is more accurate than gray-scale ultrasound of the breast for pre
      operative size assessment of invasive ductal breast carcinomas.

PMID- 17513188
TI  - MR characterization of cardiac abnormalities in HIV+ individuals with increased
      BNP levels.
AB  - OBJECTIVE: To characterize cardiac abnormalities in HIV+ patients with increased
      serum B-type natiuretic peptide (BNP) by contrast-enhanced cardiac magnetic
      resonance imaging (MRI). DESIGN: Non-blinded prospective consecutive cohort
      evaluation. METHODS: More than 400 HIV+ patients were screened for potential BNP
      alterations. 16 met the inclusion criteria of elevated BNP levels and 12 patients
      could finally be enrolled. MRI analysis comprised function, oedema and late
      enhancement sequences. RESULTS: Patients exhibited a median serum BNP level of
      249 pg/ml. Based on MRI, diagnosis of left ventricular hypertrophy (n = 3),
      myocarditis (n = 2), chronic myocardial infarction (n = 2), dilated
      cardiomyopathy (n=1) and right ventricular failure (n = 1) was made. CONCLUSIONS:
      Although no specific MR pattern was found, MR allowed characterization of the
      underlying cardiac pathologies in 82% of HIV+ patients with elevated BNP levels.

PMID- 17513189
TI  - Age dependency of intrarenal resistance index (RI) in healthy adults and patients
      with fatty liver disease.
AB  - BACKGROUND: Our aim was to investigate the influence of age and gender on
      intrarenal resistance index (RI) measurements in 78 healthy subjects (46 males,
      32 females; group 1) and 35 subjects (group 2) with fatty liver disease (28 males
      and 7 females). SUBJECTS AND METHODS: First, each subject underwent a
      conventional abdominal ultrasound examination. Then, intrarenal RI values were
      determined from three distinct interlobar and cortical arteries respectively on
      both kidneys. The correlation of intrarenal RI with age and gender as a variable
      was statistically evaluated by linear regression. RESULTS: In group 1, the
      variables gender, kidney region and comparison of right versus left kidney had no
      significant effect on intrarenal RI (p>0.05). The variable age, on the other
      hand, showed a significant positive correlation on all four defined measuring
      points (p<0.01) with linear correlation coefficients of r = 0.26 (left kidney,
      central) to r = 0.37 (right kidney, cortical). Therefore normal RI values at ages
      25, 45, 65 years could be defined as 0.59, 0.61 and 0.63, respectively. Age
      dependency can thus be expressed as a function with the formula y = 0.565 +
      0.001.x. Patients with fatty liver disease showed age dependency on renal RI
      (p<0.01) as well. CONCLUSION: In accordance with other studies, the influence of
      age on intrarenal RI measurement is significant in healthy subjects. Intrarenal
      RI values from subjects with a fatty liver disease showed age dependency as well.
      Therefore it is necessary to consider the age of the examined person to interpret
      RI values correctly.

PMID- 17513190
TI  - Effectiveness of a topical salve (Dynexan) on pain sensitivity and early wound
      healing following nonsurgical periodontal therapy.
AB  - The purpose of the present study was to evaluate clinically the effect of an
      anaesthetic gel (lidocaine 20 mg/g as active agent) on pain sensitivity and early
      wound healing following nonsurgical periodontal therapy. A total of 40 patients
      with chronic periodontitis were enrolled in this randomized, split-mouth, double
      blind, placebo-controlled clinical trial. Each subject had 3 sites in each of 2
      contra-lateral jaw quadrants with a probing pocket depth (PPD) of > or = 5 mm and
      bleeding on probing (BOP+). All experimental sites received scaling and root
      planing without local anesthesia followed by irrigation with sterile saline and
      assessment of pain sensitivity using a standardized Visual Analogue Scale (VAS).
      After treatment, the patients randomly received the active or placebo gel into
      the periodontal pockets and overall pain was again assessed immediately after
      debridement and after 10, 20 and 30 minutes. The VAS showed a statistically
      significant (p < or = 0.0001) reduction in reported pain, favoring the active gel
      over the placebo at all 3 different points in time. After 30 minutes the median
      VAS score was 0.3 in the Dynexan group as opposed to 1.7 in the placebo-treated
      group (p < or = 0.0001). In terms of wound healing no differences were found
      between the test and control sites after 1 week. The results of the study showed
      that the anaesthetic gel was statistically more effective than the placebo in
      reducing pain following nonsurgical periodontal therapy. However, in terms of
      early wound healing no significant differences were seen between the two
      treatment sites.

PMID- 17513191
TI  - Inflammatory peritoneal reaction after perforated appendicitis: continuous
      peritoneal lavage versus non lavage.
AB  - INTRODUCTION: Bacterial peritonitis is a severe medical condition associated with
      a natural mortality rate of 80-100%. Progress in surgical techniques, new
      developments in intensive care medicine and antibiotic therapy reduced this rate
      significantly. Aim of this study was to evaluate sepsis parameter in perforated
      appendicitis and different postoperative management. METHODS: In 50 consecutive
      patients with diffuse bacterial peritonitis and perforated appendicitis,
      laparotomy was performed. Subsequently, 25 patients were treated with adjuvant,
      continuous peritoneal lavage (CPL) using standard peritoneal dialysis (CAPD)
      solution. The remaining 25 patients were peritoneally drained without
      postoperative irrigation (Non-CPL). In all patients endotoxin, tumor necrosis
      factor-alpha (TNF-alpha), interleukin (IL-6), C-reactive protein (CRP) and
      myeloid-related protein (MRP-8, MRP-14 and Heterocomplex) were determined.
      RESULTS: No difference in clinical outcome between CPL and Non-CPL could be
      established. An uncomplicated clinical outcome was associated with lower levels
      of inflammation markers. Furthermore, clinical data revealed that mortality
      depended on co-morbidity, and patient's age. SUMMARY: In perforated appendicitis
      a faster decrease of mediator release could not be achieved with either method.
      In addition, no difference could be established for the clinical parameters like
      hospitalization, duration of intensive care and morbidity.

PMID- 17513192
TI  - Whole-comparative genomic hybridization and "cell code" estimation: an
      application for assessment of cellular chimerism.
AB  - Whole-comparative genomic hybridization (W-CGH) allows one to identify copy
      number differences in highly repeated DNAs between two genomes. It allowed the
      identification of nuclear markers that can be used to distinguish cell
      populations from different individuals in a chimeric situation. We discuss the
      reliability of W-CGH accomplished with fluorescent in situ hybridization (FISH)
      and digital image analysis (DIA) to analyze the degree of chimerism in patients
      after allogeneic hematopoietic stem cell transplantation (HSCT).

PMID- 17513193
TI  - Prostate cancer tissue is masked by bicalutamide: a case report.
AB  - Prostate cancer is the most common malignant tumor in men. Recently, a slightly
      decreased frequency of margin positivity following neoadjuvant bicalutamide
      treatment due to tumor shrinkage was reported. Trials investigating other anti
      androgens in the past also reported lower frequencies of surgical margin
      positivity, but patients outcome has not improved. In this case, local recurrence
      was confirmed by needle biopsy in a patient five years following radical
      prostatectomy for prostate adenocarcinoma. After therapy with 50 mg bicalutamide
      for a month, the tumour was resected. Despite of detailed histological work-up
      and immunohistochemistry cancer suspicious lesions were not found. We think that
      bicalutamide may be capable of masking prostate cancer cells.

PMID- 17513194
TI  - Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1
      secretion by peripheral blood mononuclear cells in patients with primary
      nephrotic syndrome.
AB  - BACKGROUND: Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1)
      activity and/or expression are upregulated in nephrotic syndrome. Despite
      extensive research on antithrombotic effect of statins, little is known about
      their effects on TF and PAI-1 expression in peripheral blood mononuclear cells in
      patients with primary nephrotic syndrome(PNS). METHODS: PBMCs were isolated by
      gradient centrifugation from 25 individuals with PNS and 25 healthy subjects. TF
      and PAI-1 mRNA were detected by RT-PCR. The activities of TF and PAI-1 were
      determined with ELISA and chromogenic substrate method, respectively. The
      patients with PNS were then treated with simvastatin 40 mg/day for 2 weeks. The
      activities of TF, PAI-1 and TF, PAI-1 mRNA of PBMCs were also measured. RESULTS:
      Compared with controls, patients with PNS had increased TF, PAI-1 secretion by
      PBMCs at baseline (70.4 +/- 15.6 ng/l vs. 32.7 +/- 8.2 ng/l; 15.9 +/- 2.4 (x10(3)
      AU/l) vs. 3.9 +/- 1.5(x10(3) AU/l), P<0.01) and after stimulated by LPS (10
      ng/mL) (89.2 +/- 13.4 ng/l vs. 49.5 +/- 10.3 ng/l; 23.8 +/- 3.3 (x10(3) AU/l) vs.
      8.1 +/- 2.1, P<0.01). The simvastatin treatment resulted in a significant effect
      in decreasing TF and PAI-1 (69.1 +/- 14.6 ng/l vs. 89.2 +/- 13.4 ng/l; 16.5 +/-
      4.8 (x10(3) AU/l) vs. 23.8 +/- 3.3 (x10(3) AU/l), P<0.05) secretion in PBMCs.
      Increased TF and PAI-1 mRNA expression in PBMCs from PNS (1.034 +/- 0.043 and
      0.982 +/- 0.056, respectively) as compared to the control (0.221 +/- 0.015 and
      0.221 +/- 0.015, respectively) (p<0.01). two-week simvastatin treatment resulted
      in significant decrease of TF (0.535 +/- 0.028, p<0.01) and PAI-1 mRNA (0.602 +/-
      0.037, p<0.01). CONCLUSION: TF and PAI-1 mRNA expression and activities in PBMCs
      were increased in PNS. Simvastatin reduced TF and PAI-1 expression and activity
      in PBMCs. These effects may partially be relevant to the clinical benefits of
      statins in the treatment of PNS.

PMID- 17513195
TI  - Natural history and surgical treatment of brown tumor lesions at various sites in
      refractory primary hyperparathyroidism.
AB  - OBJECTIVE: Nowadays, the occurrence of brown tumor lesions or osteitis fibrosa
      cystica caused by long-lasting primary hyperparathyroidism are very rare, since
      measuring serum calcium became available routinely in the mid-1970s. It is a
      tumor-like lesion that may affect the entire skeleton, often presenting with
      diffuse focal bone pain or by pathological fracture. METHODS: We describe our
      experience of brown tumor lesions at different skeletal sites that were treated
      at our trauma centre within the last two years. This included surgical therapy
      for the indications (i) pain at the pelvis, (ii) increased risk for pathological
      fracture at the tibia and (iii) acute radicular symptoms at the lumbar spine. The
      literature was reviewed for the current understanding of the pathophysiology as
      well as therapy of brown tumor lesions in primary hyperparathyroidism. RESULTS:
      Curettage of a left-sided iliac crest brown tumor terminated focal pain. A less
      invasive stabilisation system and bone cement decreased both patient pain and the
      fracture risk of brown tumor lesion sites of the shinbone; and internal fixator
      including laminectomy at the lumbar spine ended radicular symptoms. CONCLUSION:
      Patients with refractory primary hyperparathyroidism should be monitored closely
      by endocrinologists and the patient's serum calcium level should be adjusted as
      far as possible. Radiography is required only if focal bone pain or pathological
      fractures or radicular symptoms occur. Surgery should be considered if large bone
      defects with spontaneous fracture risk or increasing pain are present. Tumor
      curettage, Palacos plombage and less invasive stabilisation systems have proved
      to be acceptable surgical options.

PMID- 17513196
TI  - Comorbidity implications in brain disease: neuronal substrates of symptom
      profiles.
AB  - The neuronal substrates underlying aspects of comorbidity in brain disease states
      may be described over psychiatric and neurologic conditions that include
      affective disorders, cognitive disorders, schizophrenia, obsessive-compulsive
      disorder, substance abuse disorders as well as the neurodegenerative disorders.
      Regional and circuitry analyses of biogenic amine systems that are implicated in
      neural and behavioural pathologies are elucidated using neuroimaging,
      electrophysiological, neurochemical, neuropharmacological and neurobehavioural
      methods that present demonstrations of the neuropathological phenomena, such as
      behavioural sensitisation, cognitive impairments, maladaptive reactions to
      environmental stress and serious motor deficits. Considerations of neuronal
      alterations that may or may not be associated with behavioural abnormalities
      examine differentially the implications of discrete areas within brains that have
      been assigned functional significance; in the case of the frontal lobes,
      differential deficits of ventromedial and dorsolateral prefrontal cortex may be
      associated with different aspects of cognition, affect, remission or response to
      medication thereby imparting a varying aspect to any investigation of
      comorbidity.

PMID- 17513197
TI  - Comorbidity of substance abuse with other psychiatric disorders.
AB  - Substance abuse is a frequent comorbid condition with other psychiatric disorders
      including schizophrenia and depression. These disorders may share a common
      substrate at the neurotransmitter or neurocircuit level. One candidate is
      hypofunction of the glutamate system. Several lines of evidence suggest that N
      methyl-D-aspartate (NMDA) receptors may hypofunction in schizophrenia. Thus, NMDA
      receptor antagonists are schizophrenogenic; postmortem and imaging results point
      to reduced NMDA receptor function in schizophrenic brains; a number of genes that
      have been linked to schizophrenia code for proteins that influence NMDA function;
      and there is preliminary evidence that pro-NMDA drugs may be therapeutic in the
      treatment of schizophrenia. One of the most effective therapeutics for the
      treatment of substance abuse in schizophrenic people is clozapine, and clozapine
      may act at the glycine modulatory site to enhance NMDA receptor function. This
      preliminary line of evidence may link schizophrenia and drug abuse to a common
      neurochemical base, subnormal NMDA receptor function. People with schizophrenia
      and drug abusers similarly show deficits in tasks known to be sensitive to
      ventromedial prefrontal cortical damage, and both groups show decreased
      activation in the ventral striatum during reward anticipation in functional
      magnetic resonance imaging studies. These observations implicate common
      prefrontal cortical-striatal circuits and their modulation by hippocampal
      projections in schizophrenia and substance abuse. Withdrawal from substance abuse
      and depression both have been linked to changes in the function of several
      neurotransmitters including serotonin, dopamine and glutamate. These findings
      suggest possible common substrates and novel therapeutic approaches. Further
      studies are needed to fully characterize the neurocircuits and transmitters
      involved in various psychiatric disorders and their possible common elements in
      comorbid drug abuse.

PMID- 17513198
TI  - Genetic variation and shared biological susceptibility underlying comorbidity in
      neuropsychiatry.
AB  - Genetic factors underlying alcoholism, substance abuse, antisocial and violent
      behaviour, psychosis, schizophrenia and psychopathy are emerging to implicate
      dopaminergic and cannabinoid, but also monoaminergic and glutamatergic systems
      through the maze of promoter genes and polymorphisms. Candidate gene association
      studies suggest the involvement of a range of genes in different disorders of CNS
      structure and function. Indices of comorbidity both complicate the array of gene
      involvement and provide a substrate of hazardous interactivity. The putative role
      of the serotonin transporter gene in affective-dissociative spectrum disorders
      presents both plausible genetic variation and complication of comorbidity The
      position of genetic variation is further complicated through ethnic, contextual
      and social factors that provide geometric progressions in the comordity already
      underlying diagnostic obstacles. The concept of shared biological susceptibility
      to two or more disorder conditions of comorbidity seems a recurring observation,
      e.g., bipolar disorder with alcoholism or schizophrenia with alcohol/substance
      abuse or diabetes with schizopsychotic disorder. Several lines of evidence seem
      to suggest that the factors influencing variation in one set of symptoms and
      those affecting one or more disorders are observed to a marked extent which ought
      to facilitate the search for susceptibility genes in comorbid brain disorders.
      Identification of regional genetic factors is awaited for a more compelling
      outline that ought eventually to lead to greater efficacy of symptom-disorder
      arrangements and an augmentation of current pharmacological treatment therapies.

PMID- 17513200
TI  - Antiapoptotic effects of nicotine in its protection against salsolinol-induced
      cytotoxicity.
AB  - Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline), a metabolite
      of dopamine, may act as an endogenous neurotoxin and contribute to the etiology
      of Parkinson's disease (PD). The inverse relationship between smoking and PD
      prompted our previous investigation and the report of protective effects of
      nicotine against salsolinol-induced toxicity in cultured SH-SY5Y cells (Copeland
      et al., Neurotox. Res. 8:289, 2005). These cells, derived from human
      neuroblastoma cells, express dopaminergic activity and are used as a model of
      nigral dopaminergic cells, the major site of pathology in PD. The purpose of the
      current study was to investigate whether apoptotic or antiapoptotic mechanisms
      were responsible for the observed effects of salsolinol and nicotine,
      respectively. Moreover, it was of interest to determine whether the actions of
      nicotine are mediated through nicotinic receptors. SH-SY5Y cells were exposed to
      0.4 or 0.7 mM salsolinol with and without pretreatment in combination of 0.1 mM
      nicotine and 0.1 mM mecamylamine and were exposed for 24 and 48 h. Various
      parameters including cell cycle perturbations (reflected in propidium iodide DNA
      staining); cell cycle regulator retinoblastoma protein (reflected in the Western
      blot), apoptosis (reflected in annexin V/propidium iodide staining followed by
      flow cytometry) were analyzed. Salsolinol caused an arrest of the cells in G1
      phase of cell cycle and an increase in apoptotic indices, whereas pretreatment
      with nicotine attenuated or completely blocked the effects of salsolinol.
      Nicotine effects in turn, were totally blocked by mecamylamine (0.1 mM). The
      results suggest that apoptosis is a major mechanism for salsolinol-induced
      toxicity and that antiapoptotic effects of nicotine, mediated by nicotinic
      receptors, may play a primary role in its neuroprotective effects. Hence,
      nicotinic agonists in combination with other antiapoptotic agents may be of
      substantial benefit in at least a subpopulation of Parkinson patients.

PMID- 17513199
TI  - Treatment consideration and manifest complexity in comorbid neuropsychiatric
      disorders.
AB  - Psychiatric disorders may co-occur in the same individual. These include, for
      example, substance abuse or obsessive-compulsive disorder with schizophrenia, and
      movement disorders or epilepsy with affective dysfunctional states. Medications
      may produce iatrogenic effects, for example cognitive impairments that co-occur
      with the residual symptoms of the primary disorder being treated. The observation
      of comorbid disorders in some cases may reflect diagnostic overlap. Impulsivity,
      impulsiveness or impulsive behaviour is implicated in a range of diagnostic
      conditions including substance abuse, affective disorder and obsessive-compulsive
      disorder. These observations suggest a need to re-evaluate established diagnostic
      criteria and disorder definitions, focusing instead on symptoms and symptom
      profiles.

PMID- 17513203
TI  - [Today and tomorrow of the Anadolu Kardiyoloji Dergisi].

PMID- 17513201
TI  - Acute and subacute exposure to malathion impairs aversive but not non-associative
      memory in rats.
AB  - Malathion [S-(1,2-dicarbethoxy) ethyl-0,0-dimethyl-phosphorodithioate] is an
      organophosphorus compound that is widely used as pesticide especially in
      developing countries. This pesticide affects the central nervous system by
      inhibiting acetylcholinesterase, leading to an increase of acetylcholine in the
      synaptic cleft, and subsequent activation of cholinergic muscarinic and nicotinic
      receptors. In humans, intoxication with organophosphates causes a wide range of
      neurological symptoms, including memory deficits. The present study was aimed to
      investigate the effects of the acute (1 h prior the test) and subacute (once a
      day for 28 days) exposure to malathion at doses of 25, 50, 100 and 150 mg/kg in
      rats tested in the step-down inhibitory avoidance task, open-field habituation
      and elevated plus-maze tests. Interestingly, the acute and subacute treatment
      with malathion impaired aversive-memory in the step-down inhibitory avoidance
      task, but did not alter the animal performance in the elevated plus-maze and in
      the habituation to the open-field tests, and neither modified spontaneous
      locomotion. The activity of acetylcholinesterase enzyme was significantly reduced
      after subacute, but not acute, treatment with malathion (25, 100 and 150 mg/kg).
      Our results suggest that malathion impairs aversive-memory retention but not non
      associative memory, without affecting anxiety-related behaviors. These findings
      support the view that the inhibition of acetylcholinesterase enzyme is not
      correlated with cognitive deficits observed in acute and subacute malathion
      treated rats.

PMID- 17513202
TI  - Perinatal asphyxia induces neurogenesis in hippocampus: an organotypic culture
      study.
AB  - There is clinical and experimental evidence indicating that neurocircuitries of
      the hippocampus are vulnerable to hypoxia/ischemia occurring at birth, inducing,
      upon re-oxygenation/re-circulation, delayed neuronal death, but also compensatory
      mechanisms, including neurogenesis. In the present report, perinatal asphyxia was
      induced by immersing foetuses-containing uterine horns removed from ready-to
      deliver rats into a water bath at 37 degrees C for 20 min. Some pups were
      delivered immediately after the hysterectomy to be used as non-asphyxiated
      caesarean-delivered controls. The pups were sacrificed after seven days for
      preparing organotypic hippocampal cultures. The cultures were grown on a
      coverslip in a medium-containing culture tube inserted in a hole of a roller
      device standing on the internal area of a cell incubator at 35 degrees C, 10%
      CO2. At days in vitro (DIV) 25-27, cultures were fixed for assaying cell
      proliferation and neuronal phenotype with antibodies against 5-bromo
      2'deoxyuridine (BrdU) and microtubule associated protein-2 (MAP-2), respectively.
      Confocal microscopy revealed that there was a 2-fold increase of BrdU-positive,
      but a 40% decrease of MAP-2-positive cells/mm3 in cultures from asphyxia-exposed,
      compared to that from control animals. Approximately 30% of BrdU-positive cells
      were also positive for MAP-2 (approximately 4800 cells), mainly seen in the
      dentate gyrus of the hippocampus, demonstrating a 3-fold increase of postnatal
      neurogenesis, when the total amount of double-labelled cells seen in cultures
      from asphyxia-exposed animals is compared to that from control animals.

PMID- 17513204
TI  - [The efficacy and prognostic value of heart rate variability in 24-hour and short
      time recordings for determining cardiac autonomic dysfunction in congestive heart
      failure].
AB  - OBJECTIVE: The heart rate variability (HRV) has been used in patients with heart
      failure as a non-invasive method and provided neuro-cardiovascular evaluation.
      This study was planned to determine the efficacy and prognostic value of 24-hour
      and short time HRV in autonomic dysfunction in patients with congestive heart
      failure. METHODS: Forty-six patients with symptomatic or asymptomatic left
      ventricular dysfunction (ejection fraction <40%) were included to the study. In
      the study group, 16 patients were in NYHA class I (35%), 19 - were in NYHA class
      II (41%) and 11 - were in NYHA class III (24%). In the first day, HRV was
      evaluated from the 24-hour Holter recordings. Following day; we assessed the HRV
      during: (1) 10 min of supine resting, (2) 10 min of regular breathing at a
      frequency of 20 acts/min, and (3) 10 min of passive orthostatism after tilting 80
      degrees with tilt table. RESULTS: Twenty-four hour and short time recordings of
      HRV showed significant decrease in long-term LF/HF24 (LF- low frequency, HF- high
      frequency), and short-term LF/HFsupine, LF/HFbreathing and LF/HFtilt ratios in
      patients with NYHA class III when compared with the patients in NYHA class I-II
      (p=0.0001, p=0.01, p=0.03, p=0.0001, respectively). During 446+/-186 days of
      follow-up, cardiovascular end-points occurred in 20 patients. In Cox multivariate
      analysis, significant predictors of cardiac mortality and morbidity were, reduced
      LF/HF ratio (HR=0.4, 95% CI 0.31-0.73, p=0.001) in the 24-hour recordings and low
      left ventricular ejection fraction (HR=0.9, 95% CI 0.83-0.99, p=0.03).
      CONCLUSION: Our study demonstrated that both of the methods were useful for
      assessment of cardiac autonomic dysfunction and only 24-hour recordings of HRV
      had a prognostic value.

PMID- 17513205
TI  - Comparison of traditional risk factors, natural history and angiographic findings
      between coronary heart disease patients with age <40 and >or=40 years old.
AB  - OBJECTIVE: In this study we aimed to examine the angiographic findings,
      traditional risk factors and natural history of Turkish patients <40 and >or=40
      years old with coronary heart disease (CHD). METHODS: The records of 491 patients
      with stable angina pectoris or acute coronary syndrome (ACS), who had undergone
      coronary angiography (CAG) were reviewed. The patients <40 years (group 1) and
      >or=40 years (group 2) were compared. RESULTS: The study population was
      classified as group 1 with 240 patients (mean age 35.7+/-3.4 years) and group 2
      with 251 patients (mean age 61.0+/-9.7 years). Smoking, family history,
      hypercholesterolemia, hypertriglyceridemia and low levels of high-density
      lipoprotein cholesterol were more prevalent in group 1 while diabetes mellitus,
      hypertension was higher in group 2. The common presentation among <40 years
      patients was ACS whereas stable angina was the most common presentation in
      patients >or=40 years old. Patients in group 1 showed a preponderance of single
      vessel disease whereas patients of group 2 showed dominance of multivessel
      disease. Early clinical course of patients with ACS in group 1 was better than in
      group 2. CONCLUSION: Our study shows a significantly different clinical,
      angiographic and biochemical profile in <40 years patients with CHD compared with
      >or=40 years patients. Dominance of smoking and dyslipidemias that are the
      preventable risk factors in premature CHD patients is an important threat for our
      community health. Healthy life styles should be encouraged beginning from young
      ages and new precautions about smoking must be taken.

PMID- 17513207
TI  - Effect of female gender on the outcome of coronary artery bypass surgery for left
      main coronary artery disease.
AB  - OBJECTIVE: Early mortality after coronary artery bypass grafting is generally
      higher in women than in men. This study analyzes the effect of female gender on
      early mortality of coronary artery bypass grafting particularly for left main
      coronary artery disease. METHODS: Study population consisted of 144 consecutive
      patients (33 women, 111 men) undergoing coronary artery bypass grafting for left
      main coronary artery disease. Mean follow-up was 25.1 +/- 14.0 months. Data were
      collected retrospectively and presented as mean +/- standard deviation. Survival
      analysis was done using Kaplan-Meier actuarial curve method with the log rank
      univariate test, followed by Cox's proportional rate multivariate model. RESULTS:
      Overall mortality was 7% in the patient population. Cox regression analysis
      revealed that the independent predictors of increased total mortality were female
      gender (HR 8.34, 95% CI 1.79 - 38.76, p=0.007), advanced age (HR 1.12, 95% CI
      1.02-1.23, p=0.014), degree of left main coronary artery stenosis (HR 1.068,
      95%CI 1.005-1.135, p=0.03), and left ventricular ejection fraction (HR 0.93, 95%
      CI 0.87-0.99, p=0.03). Female gender was found to be the only independent
      predictor of increased early mortality (HR 13.18, 95%CI 1.444-120.343, p=0.02).
      After discharge from the hospital, female gender was no more a predictor of
      increased mortality. CONCLUSION: According to these data, we may assume that
      female gender is related with increased mortality in coronary artery surgery for
      left main disease in the pre-discharge period however after discharge from
      hospital, long-term benefit of female survivors of coronary artery bypass
      grafting operated on for left main coronary artery disease might be as good as in
      men.

PMID- 17513206
TI  - [Serum apolipoprotein B is superior to LDL-cholesterol level in predicting
      incident coronary disease among Turks].
AB  - OBJECTIVE: To investigate the relative roles of serum apolipoprotein (apo) B and
      low density lipoprotein (LDL)-cholesterol levels in predicting incident coronary
      heart disease (CHD). Whether apo B/apo A-I ratio has advantage over apo B in this
      prediction constitutes a secondary aim. METHODS: Prospective evaluation of 1138
      men and 1210 women, aged 28-74 years participating in the TEKHARF survey 1997/98
      with a mean 5.9-years' follow-up in whom serum apo B was determined. Tertiles of
      LDL-cholesterol were formed by cut points of 130 and 100 mg/dl, and of apo B by
      120 and 95 mg/dl. Metabolic syndrome was defined by modified ATPIII criteria.
      Nonfatal CHD diagnosis was based on history of angina and myocardial
      revascularization, physical examination of the cardiovascular system and
      Minnesota coding of resting electrocardiograms. RESULTS: Apolipoprotein B showed
      significant correlations with a greater number of parameters than did LDL
      cholesterol. Incident CHD was not significantly predicted in age-adjusted
      logistic regression by LDL-cholesterol but by apo B concentrations in men with a
      relative risk (RR) 1.005. Apolipoprotein B level >120 vs <95 mg/dl retained
      significance in both genders combined, even after adjustment for waist girth and
      log C-reactive protein. The top (>1.02) compared with the bottom bracket of apo
      B/A-I ratio, though not reaching significantly predictive values among women, did
      significantly predict in men incident CHD with a RR 1.89. CONCLUSIONS:
      Apolipoprotein B, which marks small, dense LDL particles in plasma, is a better
      predictor of incident CHD than LDL-cholesterol among Turkish adults. While in the
      prediction of CHD apo B level should be preferred in women, an apo B/A-I ratio
      >1.02 has advantages over the latter in men. It is time to create the environment
      (at least in our cities) for measuring in equipped laboratories apo B, which has
      advantages over measurements that permit calculation of LDL-cholesterol.

PMID- 17513208
TI  - Analysis of intervariable relationships between major risk factors in the
      development of coronary artery disease: a classification tree approach.
AB  - OBJECTIVE: The purpose of this study is to determine how the major risk factors
      are related to each other in the development of coronary artery disease (CAD)
      using Chi-squared Automatic Interaction Detection (CHAID). METHODS: All patients
      with suspected CAD seen in the cardiology clinic between January 1999 and
      February 2003 who underwent coronary angiography were included in the study. A
      retrospective analysis was performed in 1381 patients. In all patients' sex, age,
      type II diabetes mellitus, hypercholesterolemia, systemic hypertension, smoking
      status, family history of CAD, body mass index (BMI) were assessed. RESULTS:
      According to classification tree, first-level split produced the two initial
      branches: female (unadjusted presence percentage = 48.07%) versus male
      (unadjusted presence percentage = 78.02%). For the male aged between 49-81 years
      and the female aged between 15-48, 49-60 and 61-71 years, diabetes mellitus was
      the most prominent risk factor. However, hypercholesterolemia was the best
      predicting variable for the females aged between 72-81 years. For the females of
      15-48 years and 49-60 years age categories without diabetes mellitus, smoking
      status and family history of CAD had important contribution to the model.
      CONCLUSION: Sorting the major risk factors of CAD from the most to least
      according to the classification importance was resulted as sex, age, diabetes
      mellitus, hypercholesterolemia, family history of CAD and smoking status.

PMID- 17513209
TI  - Predictive value of cardiothoracic ratio as a marker of severity of aortic
      regurgitation and mitral regurgitation.
AB  - OBJECTIVE: In this study we compared cardiothoracic ratio on chest radiography
      and left ventricular dimensions from echocardiography in patients with left heart
      valvular regurgitation. METHODS: The studied population consisted of 107 patients
      (55 male, 52 female) aged 7 to 25 years (11.6+/-4.7 years) with isolated mitral
      or aortic regurgitation. Chest radiography and echocardiographic examination were
      performed on the same day in every patient. RESULTS: Among 26 patients with
      moderate mitral regurgitation, cardiac enlargement was found in 4 (15%) patients
      on chest radiography, and in 7 (27%) patients on echocardiography. Among 25
      patients with severe mitral regurgitation, cardiothoracic ratio was normal in 20
      (80%) patients whereas cardiac enlargement was documented in 17 (68%) patients on
      echocardiography. Although there was no patient with cardiac enlargement (CE) on
      chest radiography in the groups of mild and moderate aortic regurgitation, 50% of
      patients in the group of severe aortic regurgitation had CE on chest radiography;
      cardiac enlargement was detected in 62% patients with moderate and 100% patients
      with severe aortic regurgitation on echocardiography. We found a good relation
      between the severity of valvular regurgitation, especially for aortic
      regurgitation, and CE on echocardiography; however only a poor relation was
      detected between the severity of valvular regurgitation and CE on chest
      radiography. CONCLUSION: In conclusion, prediction of severity of valvular
      regurgitation using chest radiography may lead to false interpretations and so,
      plain chest radiography may not be an essential part of the routine evaluation of
      such patients.

PMID- 17513210
TI  - Cardiothoracic ratio and left heart valves regurgitation.

PMID- 17513211
TI  - [Early and late outcomes of carotid artery stenting].
AB  - OBJECTIVE: Carotid artery stenting is a new approach alternative to surgical
      carotid endarterectomy. Cerebral protection devices improved the applicability of
      this technique. In this study, we evaluated applicability, safety and late
      clinical outcomes of percutaneous interventions for carotid artery stenosis.
      METHODS: A prospective study included 26 patients (15 female, 11 male, mean age
      70+/-16 years) undergoing percutaneous transluminal angioplasty and stenting with
      different sizes of balloons and stents for 28 internal carotid artery stenoses at
      Kadir Has University Department of Interventional Radiology between March 2002
      and December 2004. Ten patients were asymptomatic, one had amaurosis fugax, four
      had transient ischemic attack within last four months, one had drop attacks, one
      had headache, seven had the findings of hemiparesis and three had hemiplegia.
      RESULTS: Stenosis rates were calculated according to North America Symptomatic
      Carotid Endarterectomy Trial. Median stenosis rate was 85% (range: 60%-95%). All
      of the 28 internal carotid artery stenoses were managed with balloon dilatation
      and stenting (technical success rate 100%). Median residual stenosis rate after
      procedure was 14% (range: 0%-30%). Asystole developed in five patients and
      bradycardia in eight patients. Ipsilateral middle cerebral artery infarction
      occurred in two patients. One patient had intracranial reperfusion bleeding four
      hours after the procedure. No procedural death was observed within one month of
      follow-up. One patient died of myocardial infarction four months after the
      procedure. Cranial computed tomography revealed multiple metastases in one
      patient complaining of intractable headache and primary source was found to be
      pulmonary carcinoma. No stent restenosis was defined at Doppler ultrasonographic
      examinations performed 6 and 12 months after procedures with normal flow patterns
      and velocities. Two patients underwent control angiography at 12th month and
      myointimal proliferations with insignificant obstruction (25% and 30%) were
      detected. CONCLUSION: Carotid artery stenting seems to be applicable and safe
      procedure but it is associated with infrequent major complications. Results of
      studies comparing surgery and angioplasty will be helpful in defining role of
      stenting in the treatment of carotid occlusive disease.

PMID- 17513212
TI  - Coronary atherosclerosis distribution and the effect of blood glucose level on
      operative mortality/morbidity in diabetic patients undergoing coronary artery
      bypass grafting surgery: a single center experience.
AB  - OBJECTIVE: The study aim was to investigate the effect of blood glucose level on
      atherosclerotic lesion distribution and the contribution to the operative
      mortality/morbidity in diabetic patients who underwent coronary artery bypass
      grafting (CABG). METHODS: Between 1986-2003, a total of 2095 patients with
      diabetes mellitus underwent CABG. The analysis was carried out retrospectively
      from the clinical records. The patients were divided into four groups according
      to the blood glucose levels that were obtained when they first applied to
      hospital; Group 1 (492 patients with blood glucose < 120 mg/dl), group 2 (1112
      patients with blood glucose - 120-200 mg/dl, group 3 (261 patients with blood
      glucose 201-250 mg/dl) and group 4 (230 patients with blood glucose > 250 mg/dl).
      One way ANOVA test was used for the statistical analysis of continuous variables
      and Chi-square test was used for analyzing the categorical variables. RESULTS:
      Emergent operation rate due to acute ischemia gradually increased from Group 1 to
      Group 4 and reached 6.6% in Group 4 (p=0.005). Operation time and the duration of
      cardiopulmonary bypass and cross clamp were significantly longer in patients with
      high blood glucose levels (p<0.05). Necessity for inotropic drug administration
      postoperatively (p<0.05) and mechanical support (p<0.05) were significantly
      higher also. The hospital mortality in group 3 was 9.6% and in group 4 was 11.3%
      (p=0.09). No statistically significant difference was found in terms of morbidity
      between the groups (p>0.05). The multi-vessel coronary artery disease was more
      common in groups with high blood glucose level (p<0.05). As the blood glucose
      level raised, patients were more frequently (p<0.05) confronted with distal left
      anterior descending artery, middle circumflex artery and right coronary artery
      lesions. CONCLUSION: Uncontrolled blood glucose level not only increased the
      perioperative complications but also the incidence of middle and distal coronary
      artery lesions. It is necessary to diagnose and aggressively treat the high blood
      glucose level especially before the CABG.

PMID- 17513213
TI  - Evaluation of nosocomial infections following cardiovascular surgery.
AB  - OBJECTIVE: To evaluate nosocomial infections (NI) following cardiovascular
      surgery (CVS), and to share the first seven-year experience of the infection
      control commission in a private medical center. METHODS: Active prospective and
      laboratory based surveillance program of the hospital from January 1999 to
      December 2005 was used and all patients who were found to have NIs after CVS
      during their stay or readmission were included. RESULTS: A total of 14,502
      cardiovascular operations were performed and 416 (2.9%) patients had 494 NIs. The
      most prevalent infections were surgical site infections (42%) and urinary tract
      infections (22%). The most frequently isolated microorganisms were coagulase
      negative staphylococci (19%), Escherichia coli (16%) and Staphylococcus aureus
      (16%). A total of 99 patients (24%) died. The mortality rates were high in
      patients with blood-stream infections (58%) and lower respiratory tract
      infections (37%). The 2003 was the year with the lowest NI rate when compared to
      2000, 2001, 2002, 2004, and 2005 (p< 0.005). CONCLUSION: This study allowed an
      evaluation of NIs, including incidence and distribution, following CVS. While
      carrying on the studies to prevent NIs that are responsible for serious morbidity
      and mortality, risk factors also need to be identified in order to take
      preventive measures, other than the ones present.

PMID- 17513214
TI  - Intravascular ultrasound: questions and answers.
AB  - Coronary angiography is the gold standard for the detection of coronary artery
      disease, but it only gives information about the lumen of the coronary arteries.
      Intravascular ultrasound (IVUS) has provided a new perspective for imaging the
      coronary arteries. It allows assessment of not only the lumen but also the vessel
      wall and atherosclerotic plaque. In this article, we review the technique,
      measurements and current applications of IVUS imaging of the coronaries in a
      question-answer format.

PMID- 17513215
TI  - [Anxiety disorder as a potential for sudden death].
AB  - A close association between anxiety disorder and sudden death is known. If any
      underlying heart disease exists, it is easy to discuss this association. If it
      does not, it is difficult to explain anxiety disorder as a cause of sudden death.
      In case of acute anxiety, many complicated physiologic events, which have
      capacity of contributing to sudden death, occur. On the other hand, accelerated
      atherosclerosis ensues in the case of chronic anxiety, and the latter increases
      vulnerability to sudden death through development of coronary events.

PMID- 17513216
TI  - [Alternative site of ventricular pacing: right ventricular outflow tract].
AB  - The main reasons for traditional right ventricle apical pacing were first, the
      ease of implantation and second, the stability of passive-fixation leads in the
      apical trabeculae. However, apart from some specific diseases like hypertrophic
      cardiomyopathy, apical pacing often results in substantial functional,
      hemodynamic, electrical, and structural changes as previously demonstrated in
      many studies. Only in recent years, interest in the use of alternate pacing sites
      has developed. Right ventricular outflow tract is the preferred site of pacing
      because of its potential advantages such as ease of application, better
      hemodynamics, synchronous activation, less myocardial perfusion defects than
      apical pacing. The present review article comprehensively discusses this novel
      technique in terms of its beneficial effects compared to apical pacing and as an
      alternative method for biventricular pacing.

PMID- 17513217
TI  - Transient left ventricular apical ballooning syndrome: first series in Turkish
      patients.

PMID- 17513218
TI  - Asymmetric septal hypertrophy with perimembranous septal defect and obstructive
      right ventricular outflow tract in a patient with hypertrophic cardiomyopathy.

PMID- 17513219
TI  - Spontaneous multivessel coronary artery dissection in a wrestler.

PMID- 17513220
TI  - Early double valve re-replacement after Ross operation.

PMID- 17513221
TI  - The question of preference for Ross operation in adolescents.

PMID- 17513222
TI  - Cor triatriatum sinistrum in adults: surgical treatment of two cases.

PMID- 17513223
TI  - Giant pulmonary artery aneurysm due to undiagnosed atrial septal defect
      associated with pulmonary hypertension.

PMID- 17513224
TI  - Left pericardial agenesis in a patient with sinus venosus type atrial septal
      defect.

PMID- 17513225
TI  - [The comparison of logistic regression model selection methods for the prediction
      of coronary artery disease].

PMID- 17513226
TI  - [Relationship between the blood pressure level and the skinfold thickness].

PMID- 17513227
TI  - [Importance of metabolic syndrome definitions in prediction of cardiometabolic
      risk/ prospective validation in identical Turkish cohort of two metabolic
      syndrome definitions for predicting cardiometabolic risk and selection of most
      appropriate definition].

PMID- 17513228
TI  - [On the criteria of metabolic syndrome in predicting incident coronary disease
      and diabetes in Turkish adults/abdominal obesity and cardiometabolic risk].

PMID- 17513229
TI  - [Antithrombotic therapy in atrial fibrillation with ximelagatran: can it be an
      alternative to warfarin?].

PMID- 17513230
TI  - [Antithrombotic therapy in atrial fibrillation with ximelagatran: can it be an
      alternative to warfarin?].

PMID- 17513231
TI  - [Ximelagatran cannot be an alternative to standard warfarin therapy in chronic
      atrial fibrillation/ antithrombotic therapy in atrial fibrillation with
      ximelagatran: can it be an alternative to warfarin?].

PMID- 17513232
TI  - Composite graft in cases of insufficient length of internal thoracic artery.

PMID- 17513233
TI  - [Internal occluder techniques in ruptured abdominal aortic aneurysm/ intraaortic
      balloon catheter use as an occluder in ruptured abdominal aortic aneurysm].

PMID- 17513234
TI  - Frequency of microalbuminuria and its relationship with other atherosclerotic
      risk factors in nondiabetic hypertensive patients.

PMID- 17513235
TI  - An infective endocarditis case presenting with sudden unilateral loss of vision -
      the first and single symptom.

PMID- 17513236
TI  - [Role of the drug interaction between carvedilol and dobutamine in inducing of
      severe hypotension in a case with acute coronary syndrome].

PMID- 17513237
TI  - Supplementation of magnesium to warm blood hyperkalemic cardioplegia for the
      prevention of atrial fibrillation after coronary artery bypass grafting.

PMID- 17513238
TI  - Coronary artery bypass with saphenous vein graft in a middle-aged patient with
      polyarteritis nodosa.

PMID- 17513239
TI  - [Stenting the arterial duct and atrial balloon septoplasty in one performance].

PMID- 17513240
TI  - Rectus sheath hematoma due to cough attacks in an elderly patient on oral
      anticoagulant therapy.

PMID- 17513241
TI  - A patient with Turner's syndrome associated with unexplained left ventricular
      hypertrophy, severe left ventricular systolic dysfunction, atrial septal defect
      and pericardial effusion.

PMID- 17513242
TI  - Silent right atrial rupture detected by live three-dimensional echocardiography.

PMID- 17513243
TI  - A rare complication of aortic valve replacement surgery- aorta-right ventricular
      fistula: an evaluation with real-time multiplane echocardiography.

PMID- 17513244
TI  - Catastrophic clinical course due to free-floating large right atrial thrombus.

PMID- 17513245
TI  - A case of a single coronary artery originating from left coronary sinus of
      Valsalva associated with serious coronary artery disease.

PMID- 17513246
TI  - [The use of a polytetrafluoroethylene-covered stent graft to treat an infarct
      related severe atherosclerotic lesion with coronary artery aneurysm].

PMID- 17513247
TI  - Mitral valve replacement on a beating heart through right thoracotomy in a
      patient with patent coronary grafts.

PMID- 17513248
TI  - Hunting to extinction: biology and regional economy influence extinction risk and
      the impact of hunting in artiodactyls.
AB  - Half of all artiodactyls (even-toed hoofed mammals) are threatened with
      extinction, around double the mammalian average. Here, using a complete species
      level phylogeny, we construct a multivariate model to assess for the first time
      which intrinsic (biological) and extrinsic (anthropogenic and environmental)
      factors influence variation in extinction risk in artiodactyls. Globally
      artiodactyls at greatest risk live in economically less developed areas, have
      older weaning ages and smaller geographical ranges. Our findings suggest that
      identifying predictors of threat is complicated by interactions between both
      biological and anthropogenic factors, resulting in differential responses to
      threatening processes. Artiodactyl species that experience unregulated hunting
      live in significantly less economically developed areas than those that are not
      hunted; however, hunted species are more susceptible to extinction if they have
      slower reproductive rates (older weaning ages). In contrast, risk in non-hunted
      artiodactyls is unrelated to reproductive rate and more closely associated with
      the economic development of the region in which they live.

PMID- 17513249
TI  - ["Fast track" colorectal surgery].
AB  - Many factors have effect on the enhanced recovery after colon surgery. Not only
      the technical skill but the perioperative events needed to be optimized by the
      pre- and postoperative issues. Articles were obtained with search for keywords in
      Medline electronic database and evidences have been ranked according to the
      recommendation of the Oxford Evidence-Based Medicine Centre. Multicentric,
      randomised studies have proved that preoperative bowel emptying could not
      decrease the number of anastomotic insufficiency and wound infection rate; the
      use of abdominal drains is not necessary in every case; the proper, early oral
      intake is safe and well tolerated in colo-rectal surgery, and with laparoscopic
      surgery the same results can be achieved as with open ones. The evidences found
      even are not used completely. The advantage of laparoscopic surgery can be
      improved with fast track methods. To use correctly the affecting factors it is
      essential to know the current literature.

PMID- 17513250
TI  - [Mitochondrial DNA and its mutations: new advances in a new field].
AB  - The past two decades are considered as the golden age of the clinical research of
      mitochondrial DNA. The number of disease-associated pathologic variants is still
      expanding; the available knowledge about the entities caused by the abnormalities
      of the mitochondrial DNA is gradually increasing. The inheritance of the
      mitochondrial DNA exhibits maternal transmission; the properties are different
      from the nuclear genome in many respects. Albeit the establishment of correct
      diagnosis of several mitochondrial diseases still means diagnostic challenge,
      more and more entities can be identified due to the available molecular biology
      methods. Nowadays, significant progress of mitochondrial medicine can be observed
      in relation to several medical subspecialties; thus, mitochondrial
      gastroenterology, endocrinology, otology, ophthalmology, nephrology, hematology,
      oncology, reproductive medicine and psychiatry have been partially separated as
      the more or less circumscribed territory of the specific subspecialty. Besides
      the short overview of the general aspects of the mitochondrial medicine the
      present review provides an outlook to these chapters.

PMID- 17513251
TI  - [Paraneoplastic pemphigus].
AB  - Paraneoplastic pemphigus is an autoimmune bullous skin disease induced by
      underlying malignant or benign neoplasias. The diagnostic and immunological
      criteria of the disease were characterized by Anhalt et al. in 1990. Clinical
      symptoms are variable, consisting of polymorphous blistering skin eruption and
      severe, painful mucocutaneous ulcerations. In a subset of patients, only papular
      lesions develop, resembling lichen planus, or graft-versus-host disease; in some
      cases blisters may develop later. Severe dyspnea, progressive respiratory failure
      with clinical features of bronchiolitis obliterans is a rather frequent and
      severe complication. The diagnosis can be established with direct and indirect
      immunofluorescent studies and immunoblot analysis. The autoantigens identified to
      date include cytoplasmic proteins of the plakin gene family: envoplakin (210 kD),
      periplakin (190 kD), plectin (approximately 500 kD), desmoplakin I (250 kD),
      desmoplakin II (210 kD) and bullous pemphigoid antigen 1 (230 kD). The desmosomal
      cadherins: desmogleins 1 and 3, and desmocollins 2 and 3, as well as bullous
      pemphigoid antigen 2 (180 kD) and an undetermined 170-kD transmembranous antigen
      are also target autoantigens in the disease. The mortality rate is more than 90
      percent. Beside treatment of the underlying tumor, a combination of systemic
      steroids with immunomodulators, cytostatic drugs, plasmapheresis, plasma
      exchange, intravenous gammaglobulin, or anti-CD20 monoclonal antibody (rituximab)
      may be the most appropriate treatment.

PMID- 17513252
TI  - [Critical appraisal of articles about clinical audit].
AB  - OBJECTIVE: To summarize the most important criteria used in critical appraisal of
      publications about clinical audit by the review of the relevant English language
      literature. METHODS: Electronic databases, including Medline, Science Direct, and
      Ingenta Select, and Internet search were used to find relevant English language
      publication between 1985 and 2005. Hand search and the reference lists search for
      publications were also applied. In addition, researchers were also contacted for
      publications. RESULTS: The literature is surprisingly scarce about the critical
      appraisal of clinical audit publications. As a result hand search was as
      important as electronic search. The following three screening criteria can be
      used in order to critically appraise the scientific literature: (a) whether or
      not valid and relevant criteria and standards were used to evaluate clinical
      practice, (b) the criteria were used systematically on a representative sample of
      patients, and (c) the results are important and applicable (generalizable) in our
      practice. The publication is useful if it helps to improve the quality of our own
      clinical practice. CONCLUSION: Critical appraisal criteria can be used to improve
      the quality of clinical audit, and disseminate the results of audit, as well as
      find high quality evidence for designing and implementing quality improvement
      initiatives.

PMID- 17513253
TI  - [Whole body hypothermia for the treatment of hypoxic-ischaemic encephalopathy in
      term infants--a safety study in Hungary].
AB  - Hypoxic-ischaemic encephalopathy is a major cause of long-term morbidity and
      mortality in term infants. Prolonged systemic hypothermia is a promising new
      approach for reducing brain damage in neonates. OBJECTIVE: The aim of the open
      cohort-series clinical study was to collect data about the safety and technical
      feasibility of the hypothermia treatment in Hungary before joining to a
      randomised efficacy trial. METHODS: The authors treated 28 asphyxiated term
      neonates with hypothermia between 2003 and 2005. Hypothermia (rectal temperature
      33-34 degrees C) was maintained for 72 hours during continuous morphine
      analgesia. For historical control group 23 asphyxiated neonates were selected
      treated with standard therapy between 1996 and 2002. Entry criteria were the
      following: a 5-minute Apgar score 5 or less, the evidence of serious metabolic
      acidosis in the first hour of life (a BE of 15 mmol/l) and clinical sign of
      encephalopathy at the same time. Routine laboratory measurements of liver
      enzymes, renal functions, blood cell count, head ultrasound were performed daily.
      RESULTS: The anthropometric and clinical parameters (Apgar, pH, BE, neurological
      signs of encephalopathy) of the hypothermia and control infants were similar.
      There were no significant differences between the mortality of the hypothermia
      (10/28 36%) and the control (10/21 48%) groups. The clinical parameters
      (laboratory values, abnormality on the head ultrasound, incidence of serious
      hypotension, hypoglycaemia, bleeding, need for cardiovascular support, oliguria)
      and the neurological outcome after 1.5-2 year follow-up were also similar.
      CONCLUSIONS: This study demonstrated that prolonged whole body hypothermia of the
      asphyxiated neonate is safe and not associated with increased mortality and
      morbidity up to 18 month of age.

PMID- 17513254
TI  - [Crohn disease].

PMID- 17513256
TI  - ["Nothing that is human is foreign to me ..." Interview with Dr. Janos Regoly
      Merei by Gyorgyi B. Kiraly].

PMID- 17513257
TI  - Anaerobic methanotrophy and the rise of atmospheric oxygen.
AB  - In modern marine sediments, the anoxic decomposition of organic matter generates
      a significant flux of methane that is oxidized microbially with sulphate under
      the seafloor and never reaches the atmosphere. In contrast, prior to ca 2.4Gyr
      ago, the ocean had little sulphate to support anaerobic oxidation of methane
      (AOM) and the ocean should have been an important methane source. As atmospheric
      O2 and seawater sulphate levels rose on the early Earth, AOM would have
      increasingly throttled the release of methane. We use a biogeochemical model to
      simulate the response of early atmospheric O2 and CH4 to changes in marine AOM as
      sulphate levels increased. Semi-empirical relationships are used to parameterize
      global AOM rates and the evolution of sulphate levels. Despite broad
      uncertainties in these relationships, atmospheric O2 concentrations generally
      rise more rapidly and to higher levels (of order approx. 10(-3) bar versus
      approx. 10(-4) bar) as a result of including AOM in the model. Methane levels
      collapse prior to any significant rise in O2, but counter-intuitively, methane re
      rises after O2 rises to higher levels when AOM is included. As O2 concentrations
      increase, shielding of the troposphere by stratospheric ozone slows the effective
      reaction rate between oxygen and methane. This effect dominates over the decrease
      in the methane source associated with AOM. Thus, even with the inclusion of AOM,
      the simulated Late Palaeoproterozoic atmosphere has a climatologically
      significant level of methane of approximately 50ppmv.

PMID- 17513258
TI  - The stability of the stratospheric ozone layer during the end-Permian eruption of
      the Siberian Traps.
AB  - The discovery of mutated palynomorphs in end-Permian rocks led to the hypothesis
      that the eruption of the Siberian Traps through older organic-rich sediments
      synthesized and released massive quantities of organohalogens, which caused
      widespread O3 depletion and allowed increased terrestrial incidence of harmful
      ultraviolet-B radiation (UV-B, 280-315nm; Visscher et al. 2004 Proc. Natl Acad.
      Sci. USA 101, 12952-12956). Here, we use an extended version of the Cambridge two
      dimensional chemistry-transport model to evaluate quantitatively this possibility
      along with two other potential causes of O3 loss at this time: (i) direct effects
      of HCl release by the Siberian Traps and (ii) the indirect release of
      organohalogens from dispersed organic matter. According to our simulations, CH3Cl
      released from the heating of coals alone caused comparatively minor O3 depletion
      (5-20% maximum) because this mechanism fails to deliver sufficiently large
      amounts of Cl into the stratosphere. The unusual explosive nature of the Siberian
      Traps, combined with the direct release of large quantities of HCl, depleted the
      model O3 layer in the high northern latitudes by 33-55%, given a main eruptive
      phase of less than or equal to 200kyr. Nevertheless, O3 depletion was most
      extensive when HCl release from the Siberian Traps was combined with massive
      CH3Cl release synthesized from a large reservoir of dispersed organic matter in
      Siberian rocks. This suite of model experiments produced column O3 depletion of
      70-85% and 55-80% in the high northern and southern latitudes, respectively,
      given eruption durations of 100-200kyr. On longer eruption time scales of 400
      600kyr, corresponding O3 depletion was 30-40% and 20-30%, respectively.
      Calculated year-round increases in total near-surface biologically effective (BE)
      UV-B radiation following these reductions in O3 layer range from 30-60 (kJm(-2)d(
      1))BE up to 50-100 (kJm(-2)d(-1))BE. These ranges of daily UV-B doses appear
      sufficient to exert mutagenic effects on plants, especially if sustained over
      tens of thousands of years, unlike either rising temperatures or SO2
      concentrations.

PMID- 17513259
TI  - The Palaeocene-Eocene carbon isotope excursion: constraints from individual shell
      planktonic foraminifer records.
AB  - The Palaeocene-Eocene thermal maximum (PETM) is characterized by a global
      negative carbon isotope excursion (CIE) and widespread dissolution of seafloor
      carbonate sediments. The latter feature supports the hypothesis that the PETM and
      CIE were caused by the rapid release of a large mass (greater than 2000Gt C) of
      12C-enriched carbon. The source of this carbon, however, remains a mystery.
      Possible sources include volcanically driven thermal combustion of organic-rich
      sediment, dissociation of seafloor methane hydrates and desiccation and oxidation
      of soil/sediment organics. A key constraint on the source(s) is the rate at which
      the carbon was released. Fast rates would be consistent with a catastrophic
      event, e.g. massive methane hydrate dissociation, whereas slower rates might
      implicate other processes. The PETM carbon flux is currently constrained by high
      resolution marine and terrestrial records of the CIE. In pelagic bulk carbonate
      records, the onset of the CIE is often expressed as a single- or multiple-step
      excursion extending over 10(4) years. Individual planktonic shell records, in
      contrast, always show a single-step CIE, with either pre-excursion or excursion
      isotope values, but no transition values. Benthic foraminifera records, which are
      less complete owing to extinction and diminutive assemblages, show a delayed
      excursion. Here, we compile and evaluate the individual planktonic shell isotope
      data from several localities. We find that the most expanded records consistently
      show a bimodal isotope distribution pattern regardless of location, water depth
      or depositional facies. This suggests one of several possibilities: (i) the
      isotopic composition of the surface ocean/atmosphere declined in a geologic
      instant (<500yr), (ii) that during the onset of the CIE, most shells of mixed
      layer planktonic foraminifera were dissolved, or (iii) the abundances or shell
      production of these species temporarily declined, possibly due to initial pH
      changes.

PMID- 17513260
TI  - Methane and nitrous oxide in the ice core record.
AB  - Polar ice cores contain, in trapped air bubbles, an archive of the concentrations
      of stable atmospheric gases. Of the major non-CO2 greenhouse gases, methane is
      measured quite routinely, while nitrous oxide is more challenging, with some
      artefacts occurring in the ice and so far limited interpretation. In the recent
      past, the ice cores provide the only direct measure of the changes that have
      occurred during the industrial period; they show that the current concentration
      of methane in the atmosphere is far outside the range experienced in the last
      650,000 years; nitrous oxide is also elevated above its natural levels. There is
      controversy about whether changes in the pre-industrial Holocene are natural or
      anthropogenic in origin. Changes in wetland emissions are generally cited as the
      main cause of the large glacial-interglacial change in methane. However, changing
      sinks must also be considered, and the impact of possible newly described sources
      evaluated. Recent isotopic data appear to finally rule out any major impact of
      clathrate releases on methane at these time-scales. Any explanation must take
      into account that, at the rapid Dansgaard-Oeschger warmings of the last glacial
      period, methane rose by around half its glacial-interglacial range in only a few
      decades. The recent EPICA Dome C (Antarctica) record shows that methane tracked
      climate over the last 650,000 years, with lower methane concentrations in
      glacials than interglacials, and lower concentrations in cooler interglacials
      than in warmer ones. Nitrous oxide also shows Dansgaard-Oeschger and glacial
      interglacial periodicity, but the pattern is less clear.

PMID- 17513261
TI  - Marine aerosol production: a review of the current knowledge.
AB  - The current knowledge in primary and secondary marine aerosol formation is
      reviewed. For primary marine aerosol source functions, recent source functions
      have demonstrated a significant flux of submicrometre particles down to radii of
      20 nm. Moreover, the source functions derived from different techniques up to 10
      microm have come within a factor of two of each other. For secondary marine
      aerosol formation, recent advances have identified iodine oxides and isoprene
      oxidation products, in addition to sulphuric acid, as contributing to formation
      and growth, although the exact roles remains to be determined. While a multistep
      process seems to be required, isoprene oxidation products are more likely to
      participate in growth and sulphuric acid is more likely to participate in
      nucleation. Iodine oxides are likely to participate in both nucleation and
      growth.

PMID- 17513262
TI  - Interpreting satellite column observations of formaldehyde over tropical South
      America.
AB  - Space-borne column measurements of formaldehyde (HCHO), a high-yield oxidation
      product of volatile organic compounds (VOCs), represent important constraints for
      quantifying net regional fluxes of VOCs. Here, we interpret observed
      distributions of HCHO columns from the Global Ozone Monitoring Experiment (GOME)
      over tropical South America during 1997-2001. We present the first comparison of
      year-long in situ isoprene concentrations and fire-free GOME HCHO columns over a
      tropical ecosystem. GOME HCHO columns and in situ isoprene concentrations are
      elevated in the wet and dry seasons, with the highest values in the dry season.
      Previous analysis of the in situ data highlighted the possible role of drought in
      determining the elevated concentrations during the dry season, inferring the
      potential of HCHO columns to provide regional-scale constraints for estimating
      the role of drought on isoprene emissions. The agreement between the observed
      annual cycles of GOME HCHO columns and Along-Track Scanning Radiometer firecount
      data over the Amazon basin (correlations typically greater than 0.75 for a
      particular year) illustrates the potential of HCHO column to provide quantitative
      information about biomass burning emissions.

PMID- 17513263
TI  - Climate/chemistry feedbacks and biogenic emissions.
AB  - The oxidizing capacity of the atmosphere is affected by anthropogenic emissions
      and is projected to change in the future. Model calculations indicate that the
      change in surface ozone at some locations could be large and have significant
      implications for human health. The calculations depend on the precise scenarios
      used for the anthropogenic emissions and on the details of the feedback processes
      included in the model. One important factor is how natural biogenic emissions
      will change in the future. We carry out a sensitivity calculation to address the
      possible increase in isoprene emissions consequent on increased surface
      temperature in a future climate. The changes in ozone are significant but depend
      crucially on the background chemical regime. In these calculations, we find that
      increased isoprene will increase ozone in the Northern Hemisphere but decrease
      ozone in the tropics. We also consider the role of bromine compounds in
      tropospheric chemistry and consider cases where, in a future climate, the impact
      of bromine could change.

PMID- 17513264
TI  - Lifetimes and time scales in atmospheric chemistry.
AB  - Atmospheric composition is controlled by the emission, photochemistry and
      transport of many trace gases. Understanding the time scale as well as the
      chemical and spatial patterns of perturbations to trace gases is needed to
      evaluate possible environmental damage (e.g. stratospheric ozone depletion or
      climate change) caused by anthropogenic emissions. This paper reviews lessons
      learned from treating global atmospheric chemistry as a linearized system and
      analysing it in terms of eigenvalues. The results give insight into how emissions
      of one trace species cause perturbations to another and how transport and
      chemistry can alter the time scale of the overall perturbation. Further, the
      eigenvectors describe the fundamental chemical modes, or patterns, of the
      atmosphere's chemical response to perturbations.

PMID- 17513265
TI  - Trace gas emissions from the marine biosphere.
AB  - A wide variety of trace gases (e.g. dimethyl sulphide, organohalogens, ammonia,
      non-methane and oxygenated hydrocarbons, volatile oxygenated organics and nitrous
      oxide) are formed in marine waters by biological and photochemical processes.
      This leads in many, but not all, cases to supersaturation of the water relative
      to marine air concentrations and a net flux of trace gas to the atmosphere. Since
      the gases are often in their reduced forms in the water, once in the atmosphere
      they are subject to oxidation by photolysis or radical attack to form chemically
      reactive species that can affect the oxidizing capacity of the air. They can also
      lead to the formation of new particles or the growth of existing ones that can
      then contribute to both direct and indirect (via the formation of cloud
      condensation nuclei) aerosol effects on climate. These cycles are discussed with
      respect to their impacts on the chemistry of the atmosphere, climate and human
      health. This whole topic was the subject of an extensive review (Nightingale &
      Liss 2003 In Treatise in geochemistry (eds H. D. Holland & K. K. Turekian), pp.
      49-81) and what will be attempted here is a brief update of the earlier paper.
      There is no attempt to be comprehensive either in terms of gases covered or to
      give a complete review of all the recent literature. It is a personal view of
      recent advances both from my own research group as well as significant work from
      others. Questions raised at the meeting 'Trace gas biogeochemistry and global
      change' are dealt with at appropriate places in the text (rather than at the end
      of the piece). Discussion of each of the gases or group of gases is given in the
      following separate sections.

PMID- 17513266
TI  - A catchment-scale carbon and greenhouse gas budget of a subarctic landscape.
AB  - This is the first attempt to budget average current annual carbon (C) and
      associated greenhouse gas (GHG) exchanges and transfers in a subarctic landscape,
      the Lake Tornetrask catchment in northern Sweden. This is a heterogeneous area
      consisting of almost 4000 km2 of mixed heath, birch and pine forest, and mires,
      lakes and alpine ecosystems. The magnitudes of atmospheric exchange of carbon in
      the form of the GHGs, CO2 and CH4 in these various ecosystems differ
      significantly, ranging from little or no flux in barren ecosystems over a small
      CO2 sink function and low rates of CH4 exchange in the heaths to significant CO2
      uptake in the forests and also large emissions of CH4 from the mires and small
      lakes. The overall catchment budget, given the size distribution of the
      individual ecosystem types and a first approximation of run-off as dissolved
      organic carbon, reveals a landscape currently with a significant sink capacity
      for atmospheric CO2. This sink capacity is, however, extremely sensitive to
      environmental changes, particularly those that affect the birch forest ecosystem.
      Climatic drying or wetting and episodic events such as insect outbreaks may cause
      significant changes in the sink function. Changes in the sources of CH4 through
      increased permafrost melting may also easily change the sign of the current
      radiative forcing, due to the stronger impact per gram of CH4 relative to CO2.
      Hence, to access impacts on climate, the atmospheric C balance alone has to be
      weighed in a radiative forcing perspective. When considering the emissions of CH4
      from the mires and lakes as CO2 equivalents, the Tornetrask catchment is
      currently a smaller sink of radiative forcing, but it can still be estimated as
      representing the equivalent of approximately 14000 average Swedish inhabitants'
      emissions of CO2. This can be compared with the carbon emissions of less than 200
      people who live permanently in the catchment, although this comparison disregards
      substantial emissions from the non-Swedish tourism and transportation activities.

PMID- 17513267
TI  - Critical issues in trace gas biogeochemistry and global change.
AB  - The atmospheric composition of trace gases and aerosols is determined by the
      emission of compounds from the marine and terrestrial biospheres, anthropogenic
      sources and their chemistry and deposition processes. Biogenic emissions depend
      upon physiological processes and climate, and the atmospheric chemistry is
      governed by climate and feedbacks involving greenhouse gases themselves.
      Understanding and predicting the biogeochemistry of trace gases in past, present
      and future climates therefore demands an interdisciplinary approach integrating
      across physiology, atmospheric chemistry, physics and meteorology. Here, we
      highlight critical issues raised by recent findings in all of these key areas to
      provide a framework for better understanding the past and possible future
      evolution of the atmosphere. Incorporating recent experimental and observational
      findings, especially the influence of CO2 on trace gas emissions from marine
      algae and terrestrial plants, into earth system models remains a major research
      priority. As we move towards this goal, archives of the concentration and
      isotopes of N2O and CH4 from polar ice cores extending back over 650,000 years
      will provide a valuable benchmark for evaluating such models. In the Pre
      Quaternary, synthesis of theoretical modelling with geochemical and
      palaeontological evidence is also uncovering the roles played by trace gases in
      episodes of abrupt climatic warming and ozone depletion. Finally, observations
      and palaeorecords across a range of timescales allow assessment of the Earth's
      climate sensitivity, a metric influencing our ability to decide what constitutes
      'dangerous' climate change.

PMID- 17513268
TI  - Methane bubbling from northern lakes: present and future contributions to the
      global methane budget.
AB  - Large uncertainties in the budget of atmospheric methane (CH4) limit the accuracy
      of climate change projections. Here we describe and quantify an important source
      of CH4 -- point-source ebullition (bubbling) from northern lakes -- that has not
      been incorporated in previous regional or global methane budgets. Employing a
      method recently introduced to measure ebullition more accurately by taking into
      account its spatial patchiness in lakes, we estimate point-source ebullition for
      16 lakes in Alaska and Siberia that represent several common northern lake types:
      glacial, alluvial floodplain, peatland and thermokarst (thaw) lakes.
      Extrapolation of measured fluxes from these 16 sites to all lakes north of 45
      degrees N using circumpolar databases of lake and permafrost distributions
      suggests that northern lakes are a globally significant source of atmospheric
      CH4, emitting approximately 24.2+/-10.5Tg CH4yr(-1). Thermokarst lakes have
      particularly high emissions because they release CH4 produced from organic matter
      previously sequestered in permafrost. A carbon mass balance calculation of CH4
      release from thermokarst lakes on the Siberian yedoma ice complex suggests that
      these lakes alone would emit as much as approximately 49000Tg CH4 if this ice
      complex was to thaw completely. Using a space-for-time substitution based on the
      current lake distributions in permafrost-dominated and permafrost-free terrains,
      we estimate that lake emissions would be reduced by approximately 12% in a more
      probable transitional permafrost scenario and by approximately 53% in a
      'permafrost-free' Northern Hemisphere. Long-term decline in CH4 ebullition from
      lakes due to lake area loss and permafrost thaw would occur only after the large
      release of CH4 associated thermokarst lake development in the zone of continuous
      permafrost.

PMID- 17513269
TI  - Isoprene emission from terrestrial ecosystems in response to global change:
      minding the gap between models and observations.
AB  - Coupled surface-atmosphere models are being used with increased frequency to make
      predictions of tropospheric chemistry on a 'future' earth characterized by a
      warmer climate and elevated atmospheric CO2 concentration. One of the key inputs
      to these models is the emission of isoprene from forest ecosystems. Most models
      in current use rely on a scheme by which global change is coupled to changes in
      terrestrial net primary productivity (NPP) which, in turn, is coupled to changes
      in the magnitude of isoprene emissions. In this study, we conducted measurements
      of isoprene emissions at three prominent global change experiments in the United
      States. Our results showed that growth in an atmosphere of elevated CO2 inhibited
      the emission of isoprene at levels that completely compensate for possible
      increases in emission due to increases in aboveground NPP. Exposure to a
      prolonged drought caused leaves to increase their isoprene emissions despite
      reductions in photosynthesis, and presumably NPP. Thus, the current generation of
      models intended to predict the response of isoprene emission to future global
      change probably contain large errors. A framework is offered as a foundation for
      constructing new isoprene emission models based on the responses of leaf
      biochemistry to future climate change and elevated atmospheric CO2
      concentrations.

PMID- 17513270
TI  - Climate change and trace gases.
AB  - Palaeoclimate data show that the Earth's climate is remarkably sensitive to
      global forcings. Positive feedbacks predominate. This allows the entire planet to
      be whipsawed between climate states. One feedback, the 'albedo flip' property of
      ice/water, provides a powerful trigger mechanism. A climate forcing that 'flips'
      the albedo of a sufficient portion of an ice sheet can spark a cataclysm. Inertia
      of ice sheet and ocean provides only moderate delay to ice sheet disintegration
      and a burst of added global warming. Recent greenhouse gas (GHG) emissions place
      the Earth perilously close to dramatic climate change that could run out of our
      control, with great dangers for humans and other creatures. Carbon dioxide (CO2)
      is the largest human-made climate forcing, but other trace constituents are also
      important. Only intense simultaneous efforts to slow CO2 emissions and reduce non
      CO2 forcings can keep climate within or near the range of the past million years.
      The most important of the non-CO2 forcings is methane (CH4), as it causes the
      second largest human-made GHG climate forcing and is the principal cause of
      increased tropospheric ozone (O3), which is the third largest GHG forcing.
      Nitrous oxide (N2O) should also be a focus of climate mitigation efforts. Black
      carbon ('black soot') has a high global warming potential (approx. 2000, 500 and
      200 for 20, 100 and 500 years, respectively) and deserves greater attention. Some
      forcings are especially effective at high latitudes, so concerted efforts to
      reduce their emissions could preserve Arctic ice, while also having major
      benefits for human health, agricultural productivity and the global environment.

PMID- 17513271
TI  - Atmospheric aerosols versus greenhouse gases in the twenty-first century.
AB  - Looked at in a simplistic way, aerosols have counteracted the warming effects of
      greenhouse gases (GHG) over the past century. This has not only provided some
      'climate protection', but also prevented the true magnitude of the problem from
      becoming evident. In particular, it may have resulted in an underestimation of
      the sensitivity of the climate system to the effect of GHG. Over the present
      century, the role of aerosols in opposing global warming will wane, as there are
      powerful policy reasons to reduce their emissions and their atmospheric lifetimes
      are short in contrast to those of the GHG. On the other hand, aerosols will
      continue to play a role in regional climate change, especially with regard to the
      water cycle. The end of significant climate protection by atmospheric aerosols,
      combined with the potentially very high sensitivity of the climate system, makes
      sharp and prompt reductions in greenhouse gas emissions, especially CO2, very
      urgent.

PMID- 17513272
TI  - Comparing the climate effect of emissions of short- and long-lived climate
      agents.
AB  - Multi-gas climate agreements require a metric by which emissions of gases with
      different lifetimes and radiative properties can be placed on a common scale. The
      Kyoto Protocol to the United Nations Framework Convention on Climate Change uses
      the global warming potential (GWP) as such a metric. The GWP has attracted
      particular criticism as being inappropriate in the context of climate policy
      which seeks to restrict warming below a given target, because it gives equal
      weight to emissions irrespective of the target and the proximity to the target.
      The use of an alternative metric, the time-dependent global temperature change
      potential (GTP), is examined for its suitability and the prospects for it
      including very short-lived species. It retains the transparency and relative ease
      of use, which are attractive features of the GWP, but explicitly includes a
      dependence on the target of climate policy. The weighting of emissions using the
      GTP is found to be significantly dependent on the scenarios of future emissions
      and the sensitivity of the climate system. This may indicate that the use of any
      GTP-based weighting in future policymaking would necessitate regular revisions,
      as the global-mean temperature moves towards a specified target.

PMID- 17513273
TI  - Ozone and life on the Archaean Earth.
AB  - The trace gas ozone, produced in the present-day stratosphere, acts as a screen
      for UV radiation between 195 and approximately 290 nm, depending on its column
      abundance. On the anoxic Archaean Earth, such an ozone screen would not have
      existed. Although the presence of other screens, such as an organic haze, might
      have ameliorated the UV radiation flux, even assuming the worst-case scenario (no
      UV screen), it can be shown that early land masses and the photic zone of the
      oceans could have been colonized, suggesting that: (i) high UV radiation would
      not have prevented the colonization of land and (ii) it is unlikely that the
      fossil record can be used to constrain estimates of the UV radiation environment
      of the early Earth (although geochemical approaches and the study of extrasolar
      planetary atmospheres are likely to provide empirical constraints on the early
      photobiological environment).

PMID- 17513274
TI  - Constraining past global tropospheric methane budgets with carbon and hydrogen
      isotope ratios in ice.
AB  - Upon closer inspection, the classical view of the synchronous relationship
      between tropospheric methane mixing ratio and Greenland temperature observed in
      ice samples reveals clearly discernable variations in the magnitude of this
      response during the Late Pleistocene (<50kyr BP). During the Holocene this
      relationship appears to decouple, indicating that other factors have modulated
      the methane budget in the past 10kyr BP. The delta13CH4 and deltaD-CH4 of
      tropospheric methane recorded in ice samples provide a useful constraint on the
      palaeomethane budget estimations. Anticipated changes in palaeoenvironmental
      conditions are recorded as changes in the isotope signals of the methane
      precursors, which are then translated into past global delta13CH4 and deltaD-CH4
      signatures. We present the first methane budgets for the late glacial period that
      are constrained by dual stable isotopes. The overall isotope variations indicate
      that the Younger Dryas (YD) and Preindustrial Holocene have methane that is 13C-
      and 2H-enriched, relative to Modern. The shift is small for delta13CH4 (approx. 1
      per thousand) but greater for deltaD-CH4 (approx. 9 per thousand). The YD
      delta13CH4-deltaD-CH4 record shows a remarkable relationship between them from
      12.15 to 11.52kyr BP. The corresponding C- and H-isotope mass balances possibly
      indicate fluctuating emissions of thermogenic gas. This delta13CH4-deltaD-CH4
      relationship breaks down during the YD-Preboreal transition. In both age cases,
      catastrophic releases of hydrates with Archaeal isotope signatures can be ruled
      out. Thermogenic clathrate releases are possible during the YD period, but so are
      conventional natural gas seepages.

PMID- 17513276
TI  - The role of social work in the ICU: reducing family distress and facilitating end
      of-life decision-making.
AB  - The costs associated with Intensive Care Units (ICUs) are high and at times
      invasive ICU care may not be beneficial, particularly for those patients admitted
      to ICUs who have little hope of recovery. The process of clarifying medical goals
      for these patients is often facilitated by addressing psychosocial factors.
      Social workers in the ICU are uniquely qualified to assess and address many of
      the complex psychosocial circumstances and can clarify potential misperceptions,
      enhancing communication among patients (if capacitated), their families, and the
      medical team members. This can not only help improve quality of life for very
      sick and dying patients in the ICU and their families, but may also reduce the
      likelihood of decision-making conflicts from arising. Further studies need to be
      done to investigate the effectiveness of social work interventions in reducing
      family distress, avoiding care that is unwanted by patients, and demonstrating
      cost-saving benefits.

PMID- 17513277
TI  - Conversations at the end of life:the challenge to support patients who consider
      death with dignity in Oregon.
AB  - Oregon's Death with Dignity Act (ODWDA) has been in effect for eight years. The
      United States Supreme Court recently decided that Oregon's law did not violate
      the Controlled Substances Act. Other states may consider a law similar to
      Oregon's through legislative process or ballot measures. Although social work is
      not mentioned in the law, our profession interfaces with the terminally ill,
      particularly in hospice. Eighty-seven percent of those who have used the law were
      enrolled in a hospice program. As a pilot project, this article explores
      conversations that the authors have had with patients, families, team members and
      health systems in hospices and oncology settings under Oregon's unique
      environment. The following four themes emerged from these conversations: (1)
      mental health, education, choice; (2) team concerns; (3) family issues; and (4)
      values, ethics, restricted conversations and professional struggles.

PMID- 17513278
TI  - Clinical social work education in palliative and end-of-life care: relational
      approaches for advanced practitioners.
AB  - This paper describes the first post-Master's program in the US in end-of-life
      care for social workers. Developed at the Smith College School for Social Work,
      this program used innovative relational methods in student recruitment,
      curricular design, supervision, and leadership development, based upon input from
      the faculty, students, and field supervisors. Collaborations emerged with
      funders, agencies, and programs nationally. The program was based on a
      pedagogical stance that clinical work with dying people requires the capacity to
      be fully present- in individual, group, and family work; in interdisciplinary
      meetings; and in advocating for quality and equity of care-while attending to
      diverse and at-risk populations. Students deepened their clinical skills and took
      leadership in the field of end-of-life care.

PMID- 17513279
TI  - The Social Work Assessment Tool (SWAT).
AB  - This paper reports on the last of three National Hospice and Palliative Care
      Organization initiatives to move hospice and palliative care social workers into
      the patient/family outcomes arena: the development of the Social Work Assessment
      Tool. The experience of a team of practitioners and researchers is described,
      including results of two pilot studies and subsequent SWAT revisions. The major
      focus is on the current model performance improvement project, in which 19 social
      workers from 14 hospice and palliative care programs used the SWAT with 101
      patients and 81 primary caregivers for a median of 44 days. Quantitative analysis
      indicated significant improvement in SWAT scores for patients from the first to
      the second social work visit (t = -2.60, df = 47, p .01). Qualitative
      interviewing of the social workers indicated some lack of readiness in the field
      to conduct quantitative outcomes measurement. Additional measures are needed in
      addition to the SWAT, including qualitative measures, and measures of mezzo and
      macro practice. Participants indicated that the SWAT was appropriate for use with
      economically and culturally diverse clients.

PMID- 17513281
TI  - Internet-based interactive health intervention for the promotion of sensible
      drinking: patterns of use and potential impact on members of the general public.
AB  - BACKGROUND: Heavy drinking is responsible for major health and social problems.
      Brief interventions have been shown to be effective, but there have been
      difficulties in reaching those who might benefit from them. Pilot studies have
      indicated that a Web-based intervention is likely to be acceptable to heavy
      drinkers and may produce some health benefits. However, there are few data on how
      many people might use such a program, the patterns of use, and potential
      benefits. OBJECTIVES: The aim was to examine the demographic characteristics of
      users of a free, Web-based, 6-week intervention for heavy drinkers and to
      describe the methods by which users identified the site, the pattern of site use
      and attrition, the characteristics associated with completing the program, and
      the self-reported impact on alcohol-related outcomes. METHODS: Cohort study.
      Visitors to the Web site were offered screening with the Fast Alcohol Screening
      Test, and those scoring above the cutoff for risky drinking were invited to
      register with the program. Demographic information was collected routinely at
      registration, and questionnaires were completed at the end of weeks 1 and 6. The
      outcome measures assessed dependency (Short Alcohol Dependency Data
      Questionnaire), harms (modified Alcohol Problems Questionnaire), and mental
      health (Clinical Outcomes in Routine Evaluation-Outcome Measure). RESULTS: The
      records of 10,000 users were analyzed. The mean age was 37.4 years, 51.1% were
      female, 37.5% were single, and 42.4% lived with children. The majority were White
      British, lived in the United Kingdom, and reported occupations from the higher
      socioeconomic strata. Over 70% connected to the Down Your Drink (Down Your Drink)
      site from another Internet-based resource, whereas only 5.8% heard about the site
      from a health or other professional. Much of the Web site use (40%) was outside
      normal working hours. Attrition from the program was high, with only 16.5% of
      registrants completing the whole 6 weeks. For those who completed the program,
      and the final outcome measures, measures of dependency, alcohol-related problems,
      and mental health symptoms were all reduced at week 6. CONCLUSIONS: The Web-based
      intervention was highly used, and those who stayed with the program showed
      significant reductions in self-reported indicators of dependency, alcohol-related
      problems, and mental health symptoms; however, this association cannot be assumed
      to be causal. Programs of this type may have the potential to reach large numbers
      of heavy drinkers who might not otherwise seek help. There are significant
      methodological challenges and further research is needed to fully evaluate such
      interventions.

PMID- 17513282
TI  - Reach, engagement, and retention in an Internet-based weight loss program in a
      multi-site randomized controlled trial.
AB  - BACKGROUND: Research increasingly supports the conclusion that well-designed
      programs delivered over the Internet can produce significant weight loss compared
      to randomized controlled conditions. Much less is known about four important
      issues addressed in this study: (1) which recruitment methods produce higher
      eHealth participation rates, (2) which patient characteristics are related to
      enrollment, (3) which characteristics are related to level of user engagement in
      the program, and (4) which characteristics are related to continued participation
      in project assessments. METHODS: We recruited overweight members of three health
      maintenance organizations (HMOs) to participate in an entirely Internet-mediated
      weight loss program developed by HealthMedia, Inc. Two different recruitment
      methods were used: personal letters from prevention directors in each HMO, and
      general notices in member newsletters. The personal letters were sent to members
      diagnosed with diabetes or heart disease and, in one HMO, to a general membership
      sample in a particular geographic location. Data were collected in the context of
      a 2x2 randomized controlled trial, with participants assigned to receive or not
      receive a goal setting intervention and a nutrition education intervention in
      addition to the basic program. RESULTS: A total of 2311 members enrolled.
      Bivariate analyses on aggregate data revealed that personalized mailings produced
      higher enrollment rates than member newsletters and that members with diabetes or
      heart disease were more likely to enroll than those without these diagnoses. In
      addition, males, those over age 60, smokers, and those estimated to have higher
      medical expenses were less likely to enroll (all P < .001). Males and those in
      the combined intervention were less likely to engage initially, or to continue to
      be engaged with their Web program, than other participants. In terms of
      retention, multiple logistic regressions revealed that enrollees under age 60 (P
      < .001) and those with higher baseline self-efficacy were less likely to
      participate in the 12-month follow-up (P = .03), but with these exceptions, those
      participating were very similar to those not participating in the follow-up.
      CONCLUSIONS: A single personalized mailing increases enrollment in Internet-based
      weight loss. eHealth programs offer great potential for recruiting large numbers
      of participants, but they may not reach those at highest risk. Patient
      characteristics related to each of these important factors may be different, and
      more comprehensive analyses of determinants of enrollment, engagement, and
      retention in eHealth programs are needed.

PMID- 17513283
TI  - How cancer survivors provide support on cancer-related Internet mailing lists.
AB  - BACKGROUND: Internet mailing lists are an important and increasingly common way
      for cancer survivors to find information and support. Most studies of these
      mailing lists have investigated lists dedicated to one type of cancer, most often
      breast cancer. Little is known about whether the lessons learned from experiences
      with breast cancer lists apply to other cancers. OBJECTIVES: The aim of the study
      was to compare the structural characteristics of 10 Internet cancer-related
      mailing lists and identify the processes by which cancer survivors provide
      support. METHODS: We studied a systematic 9% sample of email messages sent over
      five months to 10 cancer mailing lists hosted by the Association of Cancer Online
      Resources (ACOR). Content analyses were used to compare the structural
      characteristics of the lists, including participation rates and members'
      identities as survivors or caregivers. We used thematic analyses to examine the
      types of support that list members provided through their message texts. RESULTS:
      Content analyses showed that characteristics of list members and subscriber
      participation rates varied across the lists. Thematic analyses revealed very
      little "off topic" discussion. Feedback from listowners indicated that they
      actively modeled appropriate communication on their lists and worked to keep
      discussions civil and focused. In all lists, members offered support much more
      frequently than they requested it; survivors were somewhat more likely than
      caregivers to offer rather than to ask for support. The most common topics in
      survivors' messages were about treatment information and how to communicate with
      health care providers. Although expressions of emotional support were less common
      than informational support, they appeared in all lists. Many messages that
      contained narratives of illness or treatment did not specifically ask for help
      but provided emotional support by reassuring listmates that they were not alone
      in their struggles with cancer. Survivors' explicit expressions of emotional
      support tended to be messages that encouraged active coping. Such messages also
      provided senders with opportunities to assume personally empowering "helper"
      roles that supported self-esteem. CONCLUSIONS: Many cancer survivors use the
      Internet to seek informational and emotional support. Across 10 lists for
      different cancers, informational support was the main communication style. Our
      finding of an emphasis on informational support is in contrast to most prior
      literature, which has focused on emotional support. We found the most common
      expressions of support were offers of technical information and explicit advice
      about how to communicate with health care providers. Topics and proportions of
      informational and emotional support differed across the lists. Our previous
      surveys of ACOR subscribers showed that they join the lists primarily to seek
      information; this qualitative study shows that they can and do find what they
      seek. They also find opportunities to play rewarding roles as support givers.

PMID- 17513284
TI  - User-centered research on breast cancer patient needs and preferences of an
      Internet-based clinical trial matching system.
AB  - BACKGROUND: Internet-based clinical trial matching systems have the potential to
      streamline the search process for women with breast cancer seeking alternative
      treatments. A prototype system was developed to leverage the capabilities of a
      personal health record system for the purpose of identifying clinical trials.
      OBJECTIVE: This study examines how breast cancer patients perceive and interact
      with a preliminary version of an Internet-based clinical trial matching system,
      while taking into account the demands of diagnosis and treatment decision making.
      METHODS: Breast cancer patients participated in small group discussions and
      interacted with the prototype website in a two-phase qualitative research
      process. The first phase explored the experience of breast cancer patients (n =
      8) with treatment decision making, initial responses to the idea of Internet
      based clinical trial matching systems, and reactions to the prototype site. In
      the second phase, a different set of breast cancer patients (n = 7) reviewed
      revised website content and presentation and participated in a usability test in
      which they registered on the system and completed a personal health record to set
      up the matching process. RESULTS: Participants were initially skeptical of the
      prototype system because it emphasized registration, had a complicated
      registration process, and asked for complex medical information. Changing content
      and attending to usability guidelines improved the experience for women in the
      second phase of the research and enabled the identification of functionality and
      content issues, such as lack of clear information and directions on how to use
      the system. CONCLUSIONS: This study showed that women felt favorably about the
      idea of using the Internet to search for clinical trials but that such a system
      needed to meet their expectations for credibility and privacy and be sensitive to
      their situation. Developers can meet these expectations by conforming to
      established usability guidelines and testing improvements with breast cancer
      patients. Future research is needed to verify these findings and to continue to
      improve systems of this nature.

PMID- 17513285
TI  - Pilot randomized trial of the effect of wireless telemonitoring on compliance and
      treatment efficacy in obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent and serious medical
      condition characterized by repeated complete or partial obstructions of the upper
      airway during sleep and is prevalent in 2% to 4% of working middle-aged adults.
      Nasal continuous positive airway pressure (CPAP) is the gold-standard treatment
      for OSA. Because compliance rates with CPAP therapy are disappointingly low,
      effective interventions are needed to improve CPAP compliance among patients
      diagnosed with OSA. OBJECTIVE: The aim was to determine whether wireless
      telemonitoring of CPAP compliance and efficacy data, compared to usual clinical
      care, results in higher CPAP compliance and improved OSA outcomes. METHODS: 45
      patients newly diagnosed with OSA were randomized to either telemonitored
      clinical care or usual clinical care and were followed for their first 2 months
      of treatment with CPAP therapy. CPAP therapists were not blinded to the
      participants' treatment group. RESULTS: 20 participants in each group received
      the designated intervention. Patients randomized to telemonitored clinical care
      used CPAP an average of 4.1 +/- 1.8 hours per night, while the usual clinical
      care patients averaged 2.8 +/- 2.2 hours per night (P = .07). Telemonitored
      patients used CPAP on 78% +/- 22% of the possible nights, while usual care
      patients used CPAP on 60% +/- 32% of the nights (P = .07). No statistically
      significant differences between the groups were found on measures of CPAP
      efficacy, including measures of mask leak and the Apnea-Hypopnea Index. Patients
      in the telemonitored group rated their likelihood to continue using CPAP
      significantly higher than the patients in the usual care group. Patients in both
      groups were highly satisfied with the care they received and rated themselves as
      "not concerned" that their CPAP data were being wirelessly monitored.
      CONCLUSIONS: Telemonitoring of CPAP compliance and efficacy data and rapid use of
      those data by the clinical sleep team to guide the collaborative (ie, patient and
      provider) management of CPAP treatment is as effective as usual care in improving
      compliance rates and outcomes in new CPAP users. This study was designed as a
      pilot-larger, well-powered studies are necessary to fully evaluate the clinical
      and economic efficacy of telemonitoring for this population.

PMID- 17513286
TI  - A survey of quality assurance practices in biomedical open source software
      projects.
AB  - BACKGROUND: Open source (OS) software is continuously gaining recognition and use
      in the biomedical domain, for example, in health informatics and bioinformatics.
      OBJECTIVES: Given the mission critical nature of applications in this domain and
      their potential impact on patient safety, it is important to understand to what
      degree and how effectively biomedical OS developers perform standard quality
      assurance (QA) activities such as peer reviews and testing. This would allow the
      users of biomedical OS software to better understand the quality risks, if any,
      and the developers to identify process improvement opportunities to produce
      higher quality software. METHODS: A survey of developers working on biomedical OS
      projects was conducted to examine the QA activities that are performed. We took a
      descriptive approach to summarize the implementation of QA activities and then
      examined some of the factors that may be related to the implementation of such
      practices. RESULTS: Our descriptive results show that 63% (95% CI, 54-72) of
      projects did not include peer reviews in their development process, while 82%
      (95% CI, 75-89) did include testing. Approximately 74% (95% CI, 67-81) of
      developers did not have a background in computing, 80% (95% CI, 74-87) were paid
      for their contributions to the project, and 52% (95% CI, 43-60) had PhDs. A
      multivariate logistic regression model to predict the implementation of peer
      reviews was not significant (likelihood ratio test = 16.86, 9 df, P = .051) and
      neither was a model to predict the implementation of testing (likelihood ratio
      test = 3.34, 9 df, P = .95). CONCLUSIONS: Less attention is paid to peer review
      than testing. However, the former is a complementary, and necessary, QA practice
      rather than an alternative. Therefore, one can argue that there are quality
      risks, at least at this point in time, in transitioning biomedical OS software
      into any critical settings that may have operational, financial, or safety
      implications. Developers of biomedical OS applications should invest more effort
      in implementing systemic peer review practices throughout the development and
      maintenance processes.

PMID- 17513287
TI  - Improving information technology adoption and implementation through the
      identification of appropriate benefits: creating IMPROVE-IT.
AB  - This paper describes the objectives of a collaborative initiative that attempts
      to provide the evidence that increased information technology (IT) capabilities,
      availability, and use lead directly to improved clinical quality, safety, and
      effectiveness within the inpatient hospital setting. This collaborative network
      has defined specific measurement indicators in an attempt to examine the
      existence, timing, and level of improvements in health outcomes that can be
      derived from IT investment. These indicators are in three areas: (1) IT costs
      (which includes both initial and ongoing investment), (2) IT infusion (ie, system
      availability, adoption, and deployment), and (3) health performance (eg, clinical
      efficacy, efficiency, quality, and effectiveness). Herein, we outline the
      theoretical framework, the methodology employed to create the metrics, and the
      benefits that can be obtained.

PMID- 17513288
TI  - Feature construction can improve diagnostic criteria for high-dimensional
      metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase
      deficiency.
AB  - BACKGROUND: In newborn screening with tandem mass spectrometry, multiple
      intermediary metabolites are quantified in a single analytical run for the
      diagnosis of fatty-acid oxidation disorders, organic acidurias, and
      aminoacidurias. Published diagnostic criteria for these disorders normally
      incorporate a primary metabolic marker combined with secondary markers, often
      analyte ratios, for which the markers have been chosen to reflect metabolic
      pathway deviations. METHODS: We applied a procedure to extract new markers and
      diagnostic criteria for newborn screening to the data of newborns with confirmed
      medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and a control group from
      the newborn screening program, Heidelberg, Germany. We validated the results with
      external data of the screening center in Hamburg, Germany. We extracted new
      markers by performing a systematic search for analyte combinations (features)
      with high discriminatory performance for MCADD. To select feature thresholds, we
      applied automated procedures to separate controls and cases on the basis of the
      feature values. Finally, we built classifiers from these new markers to serve as
      diagnostic criteria in screening for MCADD. RESULTS: On the basis of chi(2)
      scores, we identified approximately 800 of >628,000 new analyte combinations with
      superior discriminatory performance compared with the best published
      combinations. Classifiers built with the new features achieved diagnostic
      sensitivities and specificities approaching 100%. CONCLUSION: Feature
      construction methods provide ways to disclose information hidden in the set of
      measured analytes. Other diagnostic tasks based on high-dimensional metabolic
      data might also profit from this approach.

PMID- 17513289
TI  - Differential cross sections of neutron-induced fragment-emission reactions for a
      microdosimetry study.
AB  - Experimental differential cross sections of fragment emission (p, d, t, alpha,
      Li, Be and B), which were obtained for tens of mega electron volt neutrons on
      carbon and aluminum, using a counter telescope array and a Bragg-curve counter
      specially developed for neutron-induced reactions, are presented and compared
      with theoretical calculations using various reaction models. A calculation with
      the ISOBAR and GEM models was found to reproduce the experimental data except for
      an underestimation in non-vaporation processes. Calculations of the energy
      deposition by neutrons in a thin silicon layer show significant differences among
      the model employed.

PMID- 17513290
TI  - Indoor radon levels in primary schools of Patras, Greece.
AB  - Radon activity concentrations have been measured in 53 from a total of 66 public
      primary schools throughout of Patras, Greece, during December 1999 to May 2000
      using solid-state nuclear track detectors (LR-115 II). The indoor radon levels in
      the classrooms were generally low, ranging from 10 to 89 Bqm(-3). The mean
      (arithmetic mean) indoor concentration was 35 +/- 17 Bq m(-3) and an estimated
      annual effective dose of 0.1 +/- 0.1 mSv y(-1) was calculated for students and
      0.2 +/- 0.1 mSv y(-1) for teachers, assuming an equilibrium factor of 0.4 and
      occupancy factor of 12 and 14%, respectively. The research was also focused on
      parameters affecting radon concentration levels such as floor number of the
      classrooms and the age of the buildings in relation to building materials.

PMID- 17513291
TI  - Type testing of a new TLD for the UK Health Protection Agency.
AB  - The UK Health Protection Agency is currently commissioning a new personal
      dosimetry system based on the use of Harshaw two-element thermoluminescent
      dosemeter cards using LiF:Mg,Cu,P. Results of extensive type testing carried out
      with reference to IEC 61066, "Thermoluminescence Dosimetry Systems for Personal
      and Environmental Monitoring", have been presented.

PMID- 17513292
TI  - Measurements of the neutron dose near a 15 Mv medical linear accelerator.
AB  - In this work, simplified recombination methods for routine estimation of dose
      equivalent in mixed (gamma and neutrons) radiation field outside the irradiation
      field of linear medical accelerators is considered. The author's earlier reported
      method of H(10) measurements, involving determination of the recombination index
      of radiation quality, Q(4) by tissue-equivalent recombination chamber was
      combined with the new method for determination of the photon to neutron dose
      ratio D(X)/D(n) from the ratio of ion collection efficiencies measured in the
      investigated radiation field and in two reference fields of gamma and neutron
      radiations. The method is suitable when the neutron contribution to the total
      absorbed dose, D(n)/D, is >3%.

PMID- 17513294
TI  - The Association of Biomolecular Resource Facilities Proteomics Research Group
      2006 study: relative protein quantitation.
AB  - The determination of differences in relative protein abundance is a critical
      aspect of proteomics research that is increasingly used to answer diverse
      biological questions. The Association of Biomolecular Resource Facilities
      Proteomics Research Group 2006 study was a quantitative proteomics project in
      which the aim was to determine the identity and the relative amounts of eight
      proteins in two mixtures. There are numerous methodologies available to study the
      relative abundance of proteins between samples, but to date, there are few
      examples of studies that have compared these different approaches. For the 2006
      Proteomics Research Group study, there were 52 participants who used a wide
      variety of gel electrophoresis-, HPLC-, and mass spectrometry-based methods for
      relative quantitation. The quantitative data arising from this study were
      evaluated along with several other experimental details relevant to the
      methodologies used.

PMID- 17513293
TI  - Experimental and statistical considerations to avoid false conclusions in
      proteomics studies using differential in-gel electrophoresis.
AB  - In quantitative proteomics, the false discovery rate (FDR) can be defined as the
      number of false positives within statistically significant changes in expression.
      False positives accumulate during the simultaneous testing of expression changes
      across hundreds or thousands of protein or peptide species when univariate tests
      such as the Student's t test are used. Currently most researchers rely solely on
      the estimation of p values and a significance threshold, but this approach may
      result in false positives because it does not account for the multiple testing
      effect. For each species, a measure of significance in terms of the FDR can be
      calculated, producing individual q values. The q value maintains power by
      allowing the investigator to achieve an acceptable level of true or false
      positives within the calls of significance. The q value approach relies on the
      use of the correct statistical test for the experimental design. In this
      situation, a uniform p value frequency distribution when there are no differences
      in expression between two samples should be obtained. Here we report a bias in p
      value distribution in the case of a three-dye DIGE experiment where no changes in
      expression are occurring. The bias was shown to arise from correlation in the
      data from the use of a common internal standard. With a two-dye schema, where
      each sample has its own internal standard, such bias was removed, enabling the
      application of the q value to two different proteomics studies. In the case of
      the first study, we demonstrate that 80% of calls of significance by the more
      traditional method are false positives. In the second, we show that calculating
      the q value gives the user control over the FDR. These studies demonstrate the
      power and ease of use of the q value in correcting for multiple testing. This
      work also highlights the need for robust experimental design that includes the
      appropriate application of statistical procedures.

PMID- 17513295
TI  - Splicing factor 3b subunit 4 binds BMPR-IA and inhibits osteochondral cell
      differentiation.
AB  - Bone morphogenetic protein (BMP)-2/4 play critical roles in early embryogenesis
      and skeletal development. BMP-2/4 signals conduct into cells via two types of
      serine/threonine kinase receptors, known as BMPR-I (IA and IB) and BMPR-II. Here
      we identified splicing factor 3b subunit 4 (SF3b4) as a molecule that interacts
      with BMPR-IA, using a yeast two-hybrid screening with a human fetal brain cDNA
      library. Co-immunoprecipitation/immunoblot analysis confirmed their interaction
      in mammalian cells. By separation of the cell components, SF3b4 was present in
      the cell membrane fraction with BMPR-IA as well as in the nucleus. Overexpression
      of SF3b4 inhibited BMP-2-mediated osteogenic and chondrocytic differentiation of
      C2C12 and ATDC5 cells, respectively, and the endogenous expression level of SF3b4
      decreased during differentiation in ATDC5 cells. By reporter gene assay, SF3b4
      suppressed Id reporter gene activity, specific to the Smad1/5/8 pathway, but not
      TGFbeta-mediated reporter gene activity. Biotin labeling of the cell surface
      proteins followed by their immunoblot revealed that SF3b4 decreased the cell
      surface BMPRI-A levels. Further analysis by molecular modeling of the
      intracellular domain of BMPR-IA, coupled with binding studies of its several
      mutants, indicated that the site(s) for SF3b4 binding is not directly associated
      with the C-terminal lobe and the activation segment. Taken together, these
      results suggest that SF3b4, known to be localized in the nucleus and involved in
      RNA splicing, binds BMPR-IA and specifically inhibits BMP-mediated osteochondral
      cell differentiation.

PMID- 17513296
TI  - Heat shock protein 75 (TRAP1) antagonizes reactive oxygen species generation and
      protects cells from granzyme M-mediated apoptosis.
AB  - Natural killer (NK) cells play an important role in innate immunity against
      virally infected or transformed cells as the first defense line. Granzyme M
      (GzmM) is an orphan granzyme that is constitutively highly expressed in NK cells
      and is consistent with NK cell-mediated cytolysis. We recently demonstrated that
      GzmM induces caspase-dependent apoptosis with DNA fragmentation through direct
      cleavage of inhibitor of caspase-activated DNase (ICAD). However, the molecular
      mechanisms for GzmM-induced apoptosis are unclear. We found GzmM causes
      mitochondrial swelling and loss of mitochondrial transmembrane potential.
      Moreover, GzmM initiates reactive oxygen species (ROS) generation and cytochrome
      c release. Heat shock protein 75 (HSP75, also known as TRAP1) acts as an
      antagonist of ROS and protects cells from GzmM-mediated apoptosis. GzmM cleaves
      TRAP1 and abolishes its antagonistic function to ROS, resulting in ROS
      accumulation. Silencing TRAP1 through RNA interference increases ROS
      accumulation, whereas TRAP1 overexpression attenuates ROS production. ROS
      accumulation is in accordance with the release of cytochrome c from mitochondria
      and enhances GzmM-mediated apoptosis.

PMID- 17513297
TI  - Inhibition of phosphatidylinositol-3-OH kinase/Akt signaling impairs DNA repair
      in glioblastoma cells following ionizing radiation.
AB  - Radiation therapy is a mainstay in the treatment of glioblastomas, but these
      tumors are often associated with radioresistance. Activation of the
      phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway, which occurs frequently in
      glioblastomas due to inactivation of the tumor suppressor phosphatase and tensin
      homologue (PTEN), correlates with radioresistance. To directly test the link
      between Akt activation and radioresistance, we utilized PTEN-deficient U251
      glioblastoma cells engineered to inducibly restore PTEN upon exposure to
      doxycycline. These cells showed high basal levels of Akt activation (i.e. high
      levels of phospho-Akt), but induction of PTEN led to substantially decreased
      phospho-Akt and was associated with radiosensitization. To investigate whether
      the PTEN-induced radiosensitization was attributable to impaired sensing versus
      repair of DNA damage, we assessed levels of gamma-H2AX after ionizing radiation
      in U251 cells induced for PTEN. Initial post-radiation levels of gamma-H2AX foci
      were not decreased in PTEN-induced cells; however, the resolution of these foci
      was significantly delayed. In contrast to these results, induction of phosphatase
      dead PTEN showed no appreciable effect. Finally, exposure of cells to the PI3K
      inhibitor LY294002 did not decrease the occurrence of gamma-H2AX foci after
      irradiation but did markedly delay their resolution. These results together
      support a direct link between Akt activation, repair of DNA damage, and
      radioresistance in glioblastoma. Targeting the PI3K/Akt pathway may modulate DNA
      repair to improve the efficacy of radiation therapy.

PMID- 17513298
TI  - Amyotrophic lateral sclerosis-associated copper/zinc superoxide dismutase
      mutations preferentially reduce the repulsive charge of the proteins.
AB  - We provide bioinformatical evidence that protein charge plays a key role in the
      disease mechanism of amyotrophic lateral sclerosis (ALS). Analysis of 100 ALS
      associated mutations in copper/zinc superoxide dismutase (SOD1) shows that these
      are site-selective with a preference to decrease the proteins' net repulsive
      charge. For each SOD1 monomer this charge is normally -6. Because biomolecules as
      a rule maintain net negative charge to assure solubility in the cellular
      interior, the result lends support to the hypothesis of protein aggregation as an
      initiating event in the ALS pathogenesis. The strength of the preferential
      reduction of repulsive charge is higher in SOD1-associated ALS than in other
      inherited protein disorders.

PMID- 17513299
TI  - The MIG-2/integrin interaction strengthens cell-matrix adhesion and modulates
      cell motility.
AB  - Integrin-mediated cell-matrix adhesion plays an important role in control of cell
      behavior. We report here that MIG-2, a widely expressed focal adhesion protein,
      interacts with beta1 and beta3 integrin cytoplasmic domains. Integrin binding is
      mediated by a single site within the MIG-2 FERM domain. Functionally, the MIG
      2/integrin interaction recruits MIG-2 to focal adhesions. Furthermore, using
      alphaIIbbeta3 integrin-expressing Chinese hamster ovary cells, a well described
      model system for integrin activation, we show that MIG-2 promotes integrin
      activation and enhances cell-extracellular matrix adhesion. Although MIG-2 is
      expressed in many cell types, it is deficient in certain colon cancer cells.
      Expression of MIG-2, but not of an integrin binding-defective MIG-2 mutant, in
      MIG-2-null colon cancer cells strengthened cell-matrix adhesion, promoted focal
      adhesion formation, and reduced cell motility. These results suggest that the MIG
      2/integrin interaction is an important element in the cellular control of
      integrin-mediated cell-matrix adhesion and that loss of this interaction likely
      contributes to high motility of colon cancer cells.

PMID- 17513300
TI  - The active conformation of beta-arrestin1: direct evidence for the phosphate
      sensor in the N-domain and conformational differences in the active states of
      beta-arrestins1 and -2.
AB  - beta-Arrestins are multifunctional adaptor proteins that regulate seven
      transmembrane-spanning receptor (7TMR) desensitization and internalization and
      also initiate alternative signaling pathways. Studies have shown that beta
      arrestins undergo a conformational change upon interaction with agonist-occupied,
      phosphorylated 7TMRs. Although conformational changes have been reported for
      visual arrestin and beta-arrestin2, these studies are not representative of
      conformational changes in beta-arrestin1. Accordingly, in this study, we
      determine conformational changes in beta-arrestin1 using limited tryptic
      proteolysis and matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry analysis in the presence of a phosphopeptide derived from the C
      terminus of the V(2) vasopressin receptor (V(2)Rpp) or the corresponding
      unphosphorylated peptide (V(2)Rnp). V(2)Rpp binds specifically to beta-arrestin1
      causing significant conformational changes, whereas V(2)Rnp does not alter the
      conformation of beta-arrestin1. Upon V(2)Rpp binding, we show that the previously
      shielded Arg(393) becomes accessible, which indicates release of the C terminus.
      Moreover, we show that Arg(285) becomes more accessible, and this residue is
      located in a region of beta-arrestin1 responsible for stabilization of its polar
      core. These two findings demonstrate "activation" of beta-arrestin1, and we also
      show a functional consequence of the release of the C terminus of beta-arrestin1
      by enhanced clathrin binding. In addition, we show marked protection of the N
      domain of beta-arrestin1 in the presence of V(2)Rpp, which is consistent with
      previous studies suggesting the N-domain is responsible for recognizing
      phosphates in 7TMRs. A striking difference in conformational changes is observed
      in beta-arrestin1 when compared with beta-arrestin2, namely the flexibility of
      the interdomain hinge region. This study represents the first direct evidence
      that the "receptor-bound" conformations of beta-arrestins1 and 2 are different.

PMID- 17513301
TI  - Identification and characterization of cannabinoids that induce cell death
      through mitochondrial permeability transition in Cannabis leaf cells.
AB  - Cannabinoids are secondary metabolites stored in capitate-sessile glands on
      leaves of Cannabis sativa. We discovered that cell death is induced in the leaf
      tissues exposed to cannabinoid resin secreted from the glands, and identified
      cannabichromenic acid (CBCA) and Delta(1)-tetrahydrocannabinolic acid (THCA) as
      unique cell death mediators from the resin. These cannabinoids effectively
      induced cell death in the leaf cells or suspension-cultured cells of C. sativa,
      whereas pretreatment with the mitochondrial permeability transition (MPT)
      inhibitor cyclosporin A suppressed this cell death response. Examinations using
      isolated mitochondria demonstrated that CBCA and THCA mediate opening of MPT
      pores without requiring Ca(2+) and other cytosolic factors, resulting in high
      amplitude mitochondrial swelling, release of mitochondrial proteins (cytochrome c
      and nuclease), and irreversible loss of mitochondrial membrane potential.
      Therefore, CBCA and THCA are considered to cause serious damage to mitochondria
      through MPT. The mitochondrial damage was also confirmed by a marked decrease of
      ATP level in cannabinoid-treated suspension cells. These features are in good
      accord with those of necrotic cell death, whereas DNA degradation was also
      observed in cannabinoid-mediated cell death. However, the DNA degradation was
      catalyzed by nuclease(s) released from mitochondria during MPT, indicating that
      this reaction was not induced via a caspase-dependent apoptotic pathway.
      Furthermore, the inhibition of the DNA degradation only slightly blocked the cell
      death induced by cannabinoids. Based on these results, we conclude that CBCA and
      THCA have the ability to induce necrotic cell death via mitochondrial dysfunction
      in the leaf cells of C. sativa.

PMID- 17513302
TI  - Crystal structures of Saccharomyces cerevisiae N-myristoyltransferase with bound
      myristoyl-CoA and inhibitors reveal the functional roles of the N-terminal
      region.
AB  - Protein N-myristoylation catalyzed by myristoyl-CoA:protein N
      myristoyltransferase (NMT) plays an important role in a variety of critical
      cellular processes and thus is an attractive target for development of antifungal
      drugs. We report here three crystal structures of Saccharomyces cerevisiae NMT:
      in binary complex with myristoyl-CoA (MYA) alone and in two ternary complexes
      involving MYA and two different non-peptidic inhibitors. In all three structures,
      the majority of the N-terminal region, absent in all previously reported
      structures, forms a well defined motif that is located in the vicinity of the
      peptide substrate-binding site and is involved in the binding of MYA. The Ab
      loop, which might be involved in substrate recognition, adopts an open
      conformation, whereas a loop of the N-terminal region (residues 22-24) that
      covers the top of the substrate-binding site is in the position occupied by the
      Ab loop when in the closed conformation. Structural comparisons with other NMTs,
      together with mutagenesis data, suggest that the N-terminal region of NMT plays
      an important role in the binding of both MYA and peptide substrate, but not in
      subsequent steps of the catalytic mechanism. The two inhibitors occupy the
      peptide substrate-binding site and interact with the protein through primarily
      hydrophobic contacts. Analyses of the inhibitorenzyme interactions provide
      valuable information for further improvement of antifungal inhibitors targeting
      NMT.

PMID- 17513303
TI  - The shuttling SR protein 9G8 plays a role in translation of unspliced mRNA
      containing a constitutive transport element.
AB  - The splicing regulatory SR protein, 9G8, has recently been proposed to function
      in mRNA export in conjunction with the export protein, Tap/NXF1. Tap interacts
      directly with the Mason-Pfizer monkey virus constitutive transport element (CTE),
      an element that enables export of unspliced, intron-containing mRNA. Based on our
      previous finding that Tap can promote polysome association and translation of CTE
      RNA, we investigated the effect of 9G8 on cytoplasmic RNA fate. 9G8 was shown to
      enhance expression of unspliced RNA containing either the Mason-Pfizer monkey
      virus-CTE or the recently discovered Tap-CTE. 9G8 also enhanced polyribosome
      association of unspliced RNA containing a CTE. Hyperphosphorylated 9G8 was
      present in monosomes and small polyribosomes, whereas soluble fractions contained
      only hypophosphorylated protein. Our results are consistent with a model in which
      hypophosphorylated SR proteins remain stably associated with messenger
      ribonucleoprotein (mRNP) complexes during export and are released during
      translation initiation concomitant with increased phosphorylation. These results
      provide further evidence for crucial links between RNA splicing, export and
      translation.

PMID- 17513304
TI  - Circulating concentrations of insulin markers and coronary heart disease: a
      quantitative review of 19 Western prospective studies.
AB  - AIMS: It is uncertain whether there are associations between circulating levels
      of insulin markers and coronary heart disease (CHD) risk. We report an updated
      meta-analysis of studies of circulating levels of three insulin markers (fasting
      insulin, non-fasting insulin, and pro-insulin) and CHD risk. METHODS AND RESULTS:
      Prospective studies based in Western populations that reported on associations
      between levels of fasting insulin, non-fasting insulin, and pro-insulin and
      incident CHD [defined as non-fatal myocardial infarction (MI) or coronary death]
      were identified by computer-based searches and by manual searches of the relevant
      literature. Nineteen relevant population-based studies were identified, of which
      14 reported on fasting insulin levels involving 2649 CHD cases, eight reported on
      non-fasting insulin levels involving 1980 CHD cases and three reported on pro
      insulin levels involving 413 CHD cases. In a comparison of individuals who had
      circulating levels of each of these markers in the top third with those in the
      bottom third of the population, the odds ratio for CHD was 1.12 [95% confidence
      interval (CI): 0.98-1.28] for raised fasting insulin, 1.35 (1.14-1.60) for raised
      non-fasting insulin, and 2.23 (1.65-3.00) for raised pro-insulin. There was no
      good evidence of heterogeneity in these estimates attributable to the several
      study characteristics recorded, including sex, assay methods used, or degree of
      adjustment of risk estimates, but the available data in many of these subgroups,
      particularly by sex, are sparse. CONCLUSION: Associations between CHD risk and
      fasting or non-fasting insulin levels are likely to be more modest than
      previously suspected. Preliminary data suggest that pro-insulin levels may be
      more strongly associated with CHD risk than are insulin levels, and this
      possibility should be evaluated in larger and more rigorous studies.

PMID- 17513305
TI  - Are petals sterile stamens or bracts? The origin and evolution of petals in the
      core eudicots.
AB  - BACKGROUND: The aim of this paper is to discuss the controversial origins of
      petals from tepals or stamens and the links between the morphological expression
      of petals and floral organ identity genes in the core eudicots. SCOPE: I
      challenge the widely held classical view that petals are morphologically derived
      from stamens in the core eudicots, and sepals from tepals or bracts.
      Morphological data suggest that tepal-derived petals have evolved independently
      in the major lineages of the core eudicots (i.e. asterids, Santalales and rosids)
      from Berberidopsis-like prototypes, and that staminodial petals have arisen only
      in few isolated cases where petals had been previously lost (Caryophyllales,
      Rosales). The clear correlation between continuous changes in petal morphology,
      and a scenario that indicates numerous duplications to have taken place in genes
      controlling floral organ development, can only be fully understood within a
      phylogenetic context. B-gene expression plays a fundamental role in the evolution
      of the petals by controlling petaloidy, but it does not clarify petal homology.
      CONCLUSIONS: An increased synorganization of the flower in the core eudicots
      linked with the establishment of floral whorls restricts the petaloid gene
      expression to the second whorl, reducing the similarities of petals with tepals
      from which they were originally derived. An increased flower size linked with
      secondary polyandry or polycarpelly may lead to a breakdown of the restricted
      gene expression and a reversal to ancestral characteristics of perianth
      development. An altered 'sliding boundary' hypothesis is proposed for the core
      eudicots to explain shifts in petaloidy of the perianth and the event of
      staminodial petals. The repetitive changes of function in the perianth of the
      core eudicots are linked with shifts in petaloidy to the outer perianth whorl, or
      losses of petal or sepal whorls that can be secondarily compensated for by the
      inclusion of bracts in the flower. The origin and evolution of petals appears to
      be as complex on a molecular basis as it is from a morphological point of view.

PMID- 17513306
TI  - From forgotten taxon to a missing link? The position of the genus Verhuellia
      (piperaceae) revealed by molecules.
AB  - BACKGROUND AND AIMS: The species-poor and little-studied genus Verhuellia has
      often been treated as a synonym of the genus Peperomia, downplaying its
      significance in the relationships and evolutionary aspects in Piperaceae and
      Piperales. The lack of knowledge concerning Verhuellia is largely due to its
      restricted distribution, poorly known collection localities, limited availability
      in herbaria and absence in botanical gardens and lack of material suitable for
      molecular phylogenetic studies until recently. Because Verhuellia has some of the
      most reduced flowers in Piperales, the reconstruction of floral evolution which
      shows strong trends towards reduction in all lineages needs to be revised.
      METHODS: Verhuellia is included in a molecular phylogenetic analysis of Piperales
      (trnT-trnL-trnF and trnK/matK), based on nearly 6000 aligned characters and more
      than 1400 potentially parsimony-informative sites which were partly generated for
      the present study. Character states for stamen and carpel number are mapped on
      the combined molecular tree to reconstruct the ancestral states. KEY RESULTS: The
      genus Peperomia is generally considered to have the most reduced flowers in
      Piperales but this study shows that this is only partially true. Verhuellia, with
      almost equally reduced flowers, is not part of or sister to Peperomia as
      expected, but is revealed as sister to all other Piperaceae in all analyses,
      putting character evolution in this family and in the perianthless Piperales in a
      different light. A robust phylogenetic analysis including all relevant taxa is
      presented as a framework for inferring patterns and processes of evolution in
      Piperales and Piperaceae. CONCLUSIONS: Verhuellia is a further example of how a
      molecular phylogenetic study can elucidate the relationships of an unplaced
      taxon. When more material becomes available, it will be possible to investigate
      character evolution in Piperales more thoroughly and to answer some evolutionary
      questions concerning Piperaceae.

PMID- 17513308
TI  - Psychosocial factors affecting the therapeutic decision-making and postoperative
      mood states in Japanese breast cancer patients who underwent various types of
      surgery: body image and sexuality.
AB  - OBJECTIVE: We conducted an empirical study to clarify how psychosocial factors
      (e.g. body image and sexuality) influence therapeutic decision-making and to
      identify the factors that affect post-operative mood states in Japanese women who
      underwent various types of surgery. METHODS: One hundred and two patients who had
      undergone surgical treatment for breast cancer participated in this study. Twenty
      five patients had undergone mastectomy, 67 breast conserving treatment and 11
      skin-sparing mastectomy and immediate breast reconstruction. The participants
      were evaluated based on a battery of questionnaires including value estimates of
      decision-making factors, a shortened version of the Profile of Mood States and
      self-efficacy. RESULTS: The patients regarded the possibility of cure and
      recurrence of cancer as well as the physician's support as important, regardless
      of the treatments they had chosen. The patients that had immediate breast
      reconstruction placed significantly more importance on their body image and
      sexuality (i.e. physical appearance, attractiveness to partner and self
      evaluation of femininity and sexuality) than the mastectomy patients. After
      surgery, the former group tended to have a more negative mood on the shortened
      version of the Profile of Mood States than the latter group. Degree of self
      efficacy had a marked influence on the patients' mood after surgery. CONCLUSIONS:
      This study suggests the importance of discussing body image and sexuality that
      has tended to be disregarded in therapeutic decision-making situations in breast
      cancer patients in Japan. Self-efficacy is a crucial variable for improving mood
      after treatment.

PMID- 17513309
TI  - Risk factors for intravesical recurrence following urothelial carcinoma of the
      upper urinary tract: no relationship to the mode of surgery.
AB  - OBJECTIVE: The aim of this study was to clarify whether intravesical recurrence
      of upper urinary tract cancer after treatment is related to the mode of surgery
      or other oncological factors. METHODS: We evaluated 106 patients (mean age 70.4
      years; mean follow-up 24.0 months) who underwent surgery for the upper urinary
      tract cancer at Hiroshima University and its affiliated hospitals between January
      1995 and August 2005. Seventy-nine of the patients underwent retroperitoneoscopy
      assisted radical nephroureterectomy (RN) and 27 underwent nephroureterectomy by
      open surgery (OS). Fifty-two patients had renal pelvic tumors, 48 had ureteral
      tumors, and six had both renal pelvic and ureteral tumors. Twenty-eight (26%) of
      the 106 patients had a pre-operative history of bladder cancer. We identified the
      risk factors predicting intravesical recurrence of upper urinary tract cancer
      according to the type of previous surgery using the Kaplan-Meier method, log-rank
      test, and univariate and multivariate analysis using the Cox proportional hazards
      model. RESULTS: Thirty-one (29%) of the 106 patients developed bladder tumors
      post-operatively. The 2-year intravesical recurrence-free rate was 55% in the RN
      group and 60% in the OS group. There was no significant difference (P = 0.51, log
      rank test) in the rate of intravesical recurrence between the two groups.
      Multivariate analysis identified only a history of pre-operative bladder tumor
      (HR = 3.25, P = 0.003) as a predictor of post-operative intravesical recurrence.
      CONCLUSIONS: Intravesical recurrence after surgery for upper urinary tract cancer
      is not related to the mode of surgery (i.e. laparoscopy-assisted or open surgery)
      employed. The only risk factor for intravesical recurrence is a history of
      bladder cancer.

PMID- 17513310
TI  - A preliminary experimental study of boron neutron capture therapy for malignant
      tumors spreading in thoracic cavity.
AB  - BACKGROUND: The purpose of the present study is to verify the treatment effects
      of boron neutron capture therapy (BNCT) in ectopic tumors implanted in the
      thoracic cavity mimicking malignant pleural mesothelioma (MPM). METHODS: The
      tumor model was created by implanting murine squamous cell carcinoma cells into
      the thoracic cavity. Mice were sorted into four groups: group I for non
      treatment; group II for neutron irradiation; group III for gamma-ray irradiation;
      and group IV for BNCT irradiation. The antitumor effect was evaluated on the
      basis of the change in survival time. To assess the effects of BNCT on normal
      lung, non-tumor bearing mice were treated using the same method as done to the
      tumor-burdened mice. RESULTS: The BNCT group had a longer survival time of 31
      days (range 5 - 60), which was significantly longer than that of the non-treated
      control group (P = 0.011), but not significantly different from that of the
      neutron and gamma-ray groups (P = 0.067 and 0.094, respectively). In the BNCT and
      neutron groups, incidence of minimal lung fibrosis was significantly higher
      compared with the non-treated control group (P = 0.003 and 0.04, respectively).
      CONCLUSIONS: BNCT is a potentially promising treatment for malignant tumors
      spreading in the thoracic cavity such as MPM.

PMID- 17513307
TI  - Jasmonates: an update on biosynthesis, signal transduction and action in plant
      stress response, growth and development.
AB  - BACKGROUND: Jasmonates are ubiquitously occurring lipid-derived compounds with
      signal functions in plant responses to abiotic and biotic stresses, as well as in
      plant growth and development. Jasmonic acid and its various metabolites are
      members of the oxylipin family. Many of them alter gene expression positively or
      negatively in a regulatory network with synergistic and antagonistic effects in
      relation to other plant hormones such as salicylate, auxin, ethylene and abscisic
      acid. SCOPE: This review summarizes biosynthesis and signal transduction of
      jasmonates with emphasis on new findings in relation to enzymes, their crystal
      structure, new compounds detected in the oxylipin and jasmonate families, and
      newly found functions. CONCLUSIONS: Crystal structure of enzymes in jasmonate
      biosynthesis, increasing number of jasmonate metabolites and newly identified
      components of the jasmonate signal-transduction pathway, including specifically
      acting transcription factors, have led to new insights into jasmonate action, but
      its receptor(s) is/are still missing, in contrast to all other plant hormones.

PMID- 17513311
TI  - Group additive regression models for genomic data analysis.
AB  - One important problem in genomic research is to identify genomic features such as
      gene expression data or DNA single nucleotide polymorphisms (SNPs) that are
      related to clinical phenotypes. Often these genomic data can be naturally divided
      into biologically meaningful groups such as genes belonging to the same pathways
      or SNPs within genes. In this paper, we propose group additive regression models
      and a group gradient descent boosting procedure for identifying groups of genomic
      features that are related to clinical phenotypes. Our simulation results show
      that by dividing the variables into appropriate groups, we can obtain better
      identification of the group features that are related to the phenotypes. In
      addition, the prediction mean square errors are also smaller than the component
      wise boosting procedure. We demonstrate the application of the methods to pathway
      based analysis of microarray gene expression data of breast cancer. Results from
      analysis of a breast cancer microarray gene expression data set indicate that the
      pathways of metalloendopeptidases (MMPs) and MMP inhibitors, as well as cell
      proliferation, cell growth, and maintenance are important to breast cancer
      specific survival.

PMID- 17513312
TI  - Spatial smoothing and hot spot detection for CGH data using the fused lasso.
AB  - We apply the "fused lasso" regression method of (TSRZ2004) to the problem of "hot
      spot detection", in particular, detection of regions of gain or loss in
      comparative genomic hybridization (CGH) data. The fused lasso criterion leads to
      a convex optimization problem, and we provide a fast algorithm for its solution.
      Estimates of false-discovery rate are also provided. Our studies show that the
      new method generally outperforms competing methods for calling gains and losses
      in CGH data.

PMID- 17513313
TI  - Preventing spinal cord injuries in rugby union.

PMID- 17513314
TI  - Effect of nationwide injury prevention programme on serious spinal injuries in
      New Zealand rugby union: ecological study.
AB  - OBJECTIVE: To investigate the effect of RugbySmart, a nationwide educational
      injury prevention programme, on the frequency of spinal cord injuries. DESIGN:
      Ecological study. SETTING: New Zealand rugby union. PARTICIPANTS: Population at
      risk of injury comprised all New Zealand rugby union players. INTERVENTION: From
      2001, all New Zealand rugby coaches and referees have been required to complete
      RugbySmart, which focuses on educating rugby participants about physical
      conditioning, injury management, and safe techniques in the contact phases of
      rugby. MAIN OUTCOME MEASURES: Numbers of all spinal injuries due to participation
      in rugby union resulting in permanent disablement in 1976-2005, grouped into five
      year periods; observed compared with predicted number of spinal injuries in 2001
      5. RESULTS: Eight spinal injuries occurred in 2001-5, whereas the predicted
      number was 18.9 (relative rate=0.46, 95% confidence interval 0.19 to 1.14). Only
      one spinal injury resulted from scrums over the period; the predicted number was
      9.0 (relative rate=0.11, 0.02 to 0.74). Corresponding observed and predicted
      rates for spinal injuries resulting from other phases of play (tackle, ruck, and
      maul) were 7 and 9.0 (relative rate=0.83, 0.29 to 2.36). CONCLUSIONS: The
      introduction of the RugbySmart programme coincided with a reduction in the rate
      of disabling spinal injuries arising from scrums in rugby union. This study
      exemplifies the benefit of educational initiatives in injury prevention and the
      need for comprehensive injury surveillance systems for evaluating injury
      prevention initiatives in sport.

PMID- 17513315
TI  - Misleading promotion of drugs in Bangladesh: evidence from drug promotional
      brochures distributed to general practitioners by the pharmaceutical companies.

PMID- 17513316
TI  - Embryo development after successful somatic cell nuclear transfer to in vitro
      matured human germinal vesicle oocytes.
AB  - BACKGROUND: Somatic cell nuclear transfer (SCNT) involves the transfer of somatic
      cell nuclei into enucleated oocytes. Because human in vivo matured oocytes are
      scarcely available, we investigated whether in vitro matured (IVM) germinal
      vesicle (GV) oocytes could also support preimplantation development of human
      cloned embryos. METHODS: Three groups were used for SCNT: in vitro matured GV
      oocytes (IVM oocytes), 'in vivo' matured oocytes (in vivo oocytes) and 'failed
      fertilized' oocytes after routine-ICSI (FF oocytes). After removal of the
      chromosome-spindle complex, cumulus cell nuclei were injected, and oocytes were
      artificially activated and cultured. RESULTS: In total 61, 54 and 45 metaphase II
      oocytes were used for SCNT in the three groups, respectively. Survival and
      pronuclear rates were 59, 78 and 58% and 61, 64 and 50%, respectively. Of the 22
      activated IVM oocytes, 13 cleaved to the 2-cell stage, whereby 2 morulae were
      formed. For the in vivo oocytes, 17 of 27 activated oocytes cleaved to the 2-cell
      stage and 1 morula was observed. Cleavage to the 2-cell stage in the group of FF
      oocytes was compromised. CONCLUSIONS: To our knowledge, this is the first report
      describing development of cloned human embryos using IVM oocytes and non
      autologous transfer using a conventional method of SCNT.

PMID- 17513317
TI  - Association between susceptibility to advanced stage endometriosis and the
      genetic polymorphisms of aryl hydrocarbon receptor repressor and glutathione-S
      transferase T1 genes.
AB  - BACKGROUND: This study was performed to determine whether genetic polymorphisms
      of aryl hydrocarbon receptor repressor (AhRR), glutathione-S-transferase M1
      (GSTM1) and glutathione-S-transferase T1 (GSTT1) are associated with
      susceptibility to advanced stage endometriosis in a Korean population. METHODS:
      This study comprised 316 women with advanced stage endometriosis and 256 control
      women without endometriosis. Genotyping of the AhRR codon 185 was performed by
      real-time polymerase chain reaction (PCR) analysis. GSTM1 and GSTT1 genotyping
      for gene deletions were carried out by multiplex PCR analysis. RESULTS: G allele
      frequency at codon 185 of AhRR was increased in patients with endometriosis
      (P=0.047), and there was a trend for an association of C/G+G/G genotypes with
      risk of endometriosis (P=0.06). The proportion of null mutation at GSTT1 also
      tended to increase (P=0.06) in patients with endometriosis, whereas there was no
      difference in the genotype distribution of GSTM1 genes. Analyzing AhRR and GSTT1
      together, we found that patients with high-risk genotypes at both loci have
      increased risk of endometriosis, compared with patients without high-risk
      genotypes (P=0.015). CONCLUSIONS: These findings suggest that the AhRR codon 185
      and GSTT1 polymorphisms are associated with the risk of advanced stage
      endometriosis.

PMID- 17513318
TI  - Post-partum acquired haemophilia after IVF without recurrence during a second
      pregnancy obtained by IVF.

PMID- 17513319
TI  - Optimal ICSI timing after the first polar body extrusion in in vitro matured
      human oocytes.
AB  - BACKGROUND: This study was conducted to investigate the fertilization and embryo
      development of human oocytes injected at different time intervals after extrusion
      of the first polar body (PB) following in vitro maturation (IVM) in IVM cycles.
      Also, we evaluated whether spindle imaging could serve as a tool to determine the
      optimal ICSI time. METHODS: Oocytes were collected from 43 women with polycystic
      ovary syndrome. Metaphase I (MI) oocytes after in vitro culture for 24 h from
      germinal vesicle stage were subjected to ICSI according to time after first PB
      extrusion. The intervals were: within 1 h (n=38); 1-2 h (n=30); 2-4 h (n=26);4-6
      (n=28) and 6-8 h (n=40). In some MI oocytes, viable spindle location was
      evaluated using Polscope microscopy at different time intervals after first PB
      extrusion. RESULTS: Fertilization rate of the MI oocytes injected within 1 h
      after first PB extrusion was low (15.8; 6/38) (P<0.01 versus all other times). In
      contrast, the fertilization rate was 80, 92.3, 82.1 and 85% for oocytes injected
      1-2, 2-4, 4-6 and 6-8 h after first PB extrusion, respectively. Development of
      good-quality embryos was not significantly different among all the groups.
      Interestingly, all the oocytes injected within 1 h after first PB extrusion were
      in Telophase I. CONCLUSIONS: Human oocytes matured in vitro needed at least 1 h
      after first PB extrusion to complete nuclear maturation. Use of a live spindle
      imaging system can help to decide the timing of ICSI for oocytes matured in
      vitro.

PMID- 17513320
TI  - Prolonged myotonia and dystonia after general anaesthesia in a patient taking
      gabapentin.
AB  - This is the report of a 55-yr-old female who developed severe myotonia and
      dystonia after general anaesthesia. Before starting on gabapentin therapy for a
      neuropathic pain condition, she had undergone numerous uneventful general
      anaesthetics. Since receiving treatment with gabapentin, she has experienced
      severe movement disorders on emergence from each subsequent general anaesthetic.
      The events were unrelated to the choice of anaesthetic or anti-emetic. The most
      recent event that required a protracted stay in hospital after a day-case surgery
      is presented in detail, and the possible mechanisms to explain the interaction
      are discussed.

PMID- 17513321
TI  - More on renal disease progression: is interstitial inflammation truly protective?

PMID- 17513322
TI  - Developmental hypertension, nephrogenesis, and mother's milk: programming the
      neonate.

PMID- 17513323
TI  - Opening Pandora's box in the tight junction.

PMID- 17513324
TI  - Nephronophthisis-associated ciliopathies.
AB  - Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, represents
      the most frequent genetic cause of end-stage kidney disease in the first three
      decades of life. Contrary to polycystic kidney disease, NPHP shows normal or
      diminished kidney size, cysts are concentrated at the corticomedullary junction,
      and tubulointerstitial fibrosis is dominant. NPHP can be associated with
      retinitis pigmentosa (Senior-Loken syndrome), liver fibrosis, and cerebellar
      vermis aplasia (Joubert syndrome) in approximately 10% of patients. Positional
      cloning of six novel genes (NPHP1 through 6) as mutated in NPHP and functional
      characterization of their encoded proteins have contributed to the concept of
      "ciliopathies." It has helped advance a new unifying theory of cystic kidney
      diseases. This theory states that the products of all genes that are mutated in
      cystic kidney diseases in humans, mice, or zebrafish are expressed in primary
      cilia or centrosomes of renal epithelial cells. Primary cilia are sensory
      organelles that connect mechanosensory, visual, osmotic, and other stimuli to
      mechanisms of cell-cycle control and epithelial cell polarity. The ciliary theory
      explains the multiple organ involvement in NPHP regarding retinitis pigmentosa,
      liver fibrosis, ataxia, situs inversus, and mental retardation. Mutations in NPHP
      genes cause defects in signaling mechanisms, including the noncanonical Wnt
      signaling pathway. The "ciliopathy" NPHP thereby is caused by defects in tissue
      differentiation and maintenance as a result of impaired processing of
      extracellular cues. Nephrocystins, the proteins that are encoded by NPHP genes,
      are highly conserved in evolution. Positional cloning of additional causative
      genes of NPHP will elucidate further signaling mechanisms that are involved,
      thereby establishing therapeutic approaches using animal models in mouse,
      zebrafish, and Caenorhabditis elegans.

PMID- 17513325
TI  - A common variant of the PAX2 gene is associated with reduced newborn kidney size.
AB  - Congenital nephron number ranges widely in the human population. Suboptimal
      nephron number may be associated with increased risk for essential hypertension
      and susceptibility to renal injury, but the factors that set nephron number
      during kidney development are unknown. In renal-coloboma syndrome, renal
      hypoplasia and reduced nephron number are due to heterozygous mutations of the
      PAX2 gene. This study tested for an association between a common haplotype of the
      PAX2 gene and subtle renal hypoplasia in normal newborns. A PAX2 haplotype was
      identified to occur in 18.5% of the newborn cohort, which was significantly
      associated with a 10% reduction in newborn kidney volume adjusted for body
      surface area. This haplotype was also associated with reduced allele-specific
      PAX2 mRNA level in a human renal cell carcinoma cell line. Subtle renal
      hypoplasia in normal newborns may be partially due to a common variant of the
      PAX2 gene that reduces mRNA expression during kidney development.

PMID- 17513326
TI  - Combination therapy with an angiotensin-converting enzyme inhibitor and a vitamin
      D analog suppresses the progression of renal insufficiency in uremic rats.
AB  - Monotherapy with angiotensin-converting enzyme inhibitors has been shown to be
      beneficial in suppressing the progression of experimentally induced kidney
      diseases. Whether such therapy provides additional benefits when combined with
      vitamin D or an analog of vitamin D has not been established. Rats were made
      uremic by 5/6 nephrectomy and treated as follows: Uremic + vehicle (UC), uremic +
      enalapril (30 mg/L in drinking water; E), uremic + paricalcitol (19-nor; 0.8
      microg/kg, three times a week), and uremic + enalapril + paricalcitol (E + 19
      nor). A group of normal rats served as control (NC). BP was significantly
      elevated in the UC and 19-nor groups compared with the NC group but was
      indistinguishable from normal in the E and E + 19-nor groups. The decrease in
      creatinine clearance and the increase in the excretion of urinary protein that
      were observed in the UC group were ameliorated by the use of E alone or by E + 19
      nor (P < 0.05 versus UC). The glomerulosclerotic index was significantly
      decreased in both the 19-nor (P < 0.01) and E + 19-nor groups (P < 0.01) compared
      with the UC group. Tubulointerstitial volume was significantly decreased in both
      the E (P < 0.05) and E + 19-nor groups (P < 0.01) compared with the UC group.
      Both macrophage infiltration (ED-1-positive cells) and production of the
      chemokine monocyte chemoattractant protein-1 were significantly blunted in E + 19
      nor compared with E group. TGF-beta1 mRNA and protein expression were increased
      in the UC group (mRNA: 23.7-fold; protein: 29.1-fold versus NC). These increases
      were significantly blunted in the 19-nor group (mRNA: 7.1-fold; protein: 8.0-fold
      versus NC) and virtually normalized in the E + 19-nor group (protein: 0.8-fold
      versus NC). Phosphorylation of Smad2 was also elevated in the UC group (7.6-fold
      versus NC) but less so in the 19-nor-treated rats (5.5-fold versus NC). When rats
      were treated with E + 19-nor, the phosphorylation of Smad2 was normal (1.1-fold
      versus NC). Thus, 19-nor can suppress the progression of renal insufficiency via
      mediation of the TGF-beta signaling pathway, and this effect is amplified when BP
      is controlled via renin-angiotensin system blockade.

PMID- 17513327
TI  - IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme
      inhibitors in children and young people with IgA nephropathy and moderate
      proteinuria.
AB  - This European Community Biomedicine and Health Research-supported, multicenter,
      randomized, placebo-controlled, double-blind trial investigated the effect of an
      angiotensin-converting enzyme inhibitor (ACE-I) in children and young people with
      IgA nephropathy (IgAN), moderate proteinuria (>1 and <3.5 g/d per 1.73 m(2)) and
      creatinine clearance (CrCl) >50 ml/min per 1.73 m(2). Sixty-six patients who were
      20.5 yr of age (range 9 to 35 yr), were randomly assigned to Benazepril 0.2 mg/kg
      per d (ACE-I) or placebo and were followed for a median of 38 mo. The primary
      outcome was the progression of kidney disease, defined as >30% decrease of CrCl;
      secondary outcomes were (1) a composite end point of >30% decrease of CrCl or
      worsening of proteinuria until > or =3.5 g/d per 1.73 m(2) and (2) proteinuria
      partial remission (<0.5 g/d per 1.73 m(2)) or total remission (<160 mg/d per 1.73
      m(2)) for >6 mo. Analysis was by intention to treat. A single patient (3.1%) in
      the ACE-I group and five (14.7%) in the placebo group showed a worsening of CrCl
      >30%. The composite end point of >30% decrease of CrCl or worsening of
      proteinuria until nephrotic range was reached by one (3.1%) of 32 patients in the
      ACE-I group, and nine (26.5%) of 34 in the placebo group; the difference was
      significant (log-rank P = 0.035). A stable, partial remission of proteinuria was
      observed in 13 (40.6%) of 32 patients in the ACE-I group versus three (8.8%) of
      34 in the placebo group (log-rank P = 0.033), with total remission in 12.5% of
      ACE-I-treated patients and in none in the placebo group (log-rank P = 0.029). The
      multivariate Cox analysis showed that treatment with ACE-I was the independent
      predictor of prognosis; no influence on the composite end point was found for
      gender, age, baseline CrCl, systolic or diastolic BP, mean arterial pressure, or
      proteinuria.

PMID- 17513331
TI  - Shoulder joint loading in the high performance flat and kick tennis serves.
AB  - OBJECTIVE: To quantify and compare the full body kinematics and shoulder joint
      kinetics during the high-performance tennis flat (FS) and kick serves (KS).
      METHODS: A 12-camera 250 Hz, Vicon motion analysis system recorded the three
      dimensional FS and KS of 12 high-performance male players. A total of 22 paired
      Student's t tests, with an accompanying partial Bonferroni correction (p<0.01),
      determined statistically significant differences between the variables of
      interest in both serves. RESULTS: Higher peak horizontal, vertical and absolute
      racquet velocities were developed during the FS, while higher lateral velocities
      characterised the KS. Similar shoulder joint kinematics and kinetics punctuated
      both serves, but with some variation in trunk and lower limb mechanics.
      CONCLUSIONS: Similar shoulder joint kinetics assisted the development of varying
      three-dimensional racquet velocities in the FS and KS. The comparable shoulder
      joint loading conditions point to the repetitive, long-term performance of either
      serve as relevant in shoulder joint injury pathologies.

PMID- 17513332
TI  - Contact events in rugby union and their propensity to cause injury.
AB  - OBJECTIVE: The objective of this study was to determine the incidence of contact
      events in professional rugby union matches and to assess their propensity to
      cause injury. DESIGN: The study was a two-season (2003/2004 and 2005/2006)
      prospective cohort design. It included 645 professional rugby union players from
      13 English Premiership rugby union clubs. The main outcome measures were:
      incidence of match contact events (events per game); incidence (injuries per 1000
      player-hours and per 1000 contact events), risk (days lost per 1000 player-hours
      and per 1000 contact events) and diagnosis of injury; referee's decision. Risk
      factors were player-player contact, position on pitch and period of play.
      RESULTS: Tackles (221.0 events/game) and rucks (142.5 events/game) were the most
      common events and mauls (13.6%) and scrums (12.6%) the most penalised. Tackles
      (701.6 days/1000 player-hours) were responsible for the greatest loss of time but
      scrums (213.2 days lost/1000 events) and collisions (199.8 days lost/1000 events)
      presented the highest risk per event. CONCLUSIONS: Tackles were the game event
      responsible for the highest number of injuries and the greatest loss of time in
      rugby union because they were by far the most common contact event. Collisions
      were 70% more likely to result in an injury than a tackle and scrums carried a
      60% greater risk of injury than a tackle. The relative propensities for contact
      events to cause injury were rated as: lineout--very low; ruck--low; maul and
      tackle--average; collision and scrum--high.

PMID- 17513333
TI  - An office-place stepping device to promote workplace physical activity.
AB  - OBJECTIVE: It was proposed that an office-place stepping device is associated
      with significant and substantial increases in energy expenditure compared to
      sitting energy expenditure. The objective was to assess the effect of using an
      office-place stepping device on the energy expenditure of lean and obese office
      workers. METHODS: The office-place stepping device is an inexpensive, near
      silent, low-impact device that can be housed under a standard desk and plugged
      into an office PC for self-monitoring. Energy expenditure was measured in lean
      and obese subjects using the stepping device and during rest, sitting and
      walking. 19 subjects (27+/-9 years, 85+/-23 kg): 9 lean (BMI<25 kg/m2) and 10
      obese (BMI>29 kg/m2) attended the experimental office facility. Energy
      expenditure was measured at rest, while seated in an office chair, standing,
      walking on a treadmill and while using the office-place stepping device. RESULTS:
      The office-place stepping device was associated with an increase in energy
      expenditure above sitting in an office chair by 289+/-102 kcal/hour (p<0.001).
      The increase in energy expenditure was greater for obese (335+/-99 kcal/hour)
      than for lean subjects (235+/-80 kcal/hour; p = 0.03). The increments in energy
      expenditure were similar to exercise-style walking. CONCLUSION: The office-place
      stepping device could be an approach for office workers to increase their energy
      expenditure. If the stepping device was used to replace sitting by 2 hours per
      day and if other components of energy balance were constant, weight loss of 20
      kg/year could occur.

PMID- 17513344
TI  - Central nitric oxide blocks vasopressin, oxytocin and atrial natriuretic peptide
      release and antidiuretic and natriuretic responses induced by central angiotensin
      II in conscious rats.
AB  - The presence of nitric oxide synthase (NOS), the enzyme that catalyses the
      formation of nitric oxide (NO), in the circumventricular organs and magnocellular
      neurones suggests an important role of NO in the modulation of vasopressin (AVP)
      and oxytocin (OT) release. Intracerebroventricular (I.C.V.) injection of
      angiotensin II (Ang II) stimulates the release of AVP, OT and atrial natriuretic
      peptide (ANP), with the resultant antidiuretic and natriuretic effects. This
      study investigated the interaction between nitrergic and angiotensinergic
      pathways on the release of AVP, OT and ANP and on urinary volume and sodium
      excretion in water-loaded rats. Unanaesthetized, freely moving, male Wistar rats
      received two water loads followed by an injection into the lateral ventricle of
      an inhibitor of NOS (L-NAME), a NO donor [3-morpholinylsydnoneimine chloride (SIN
      1) or S-nitroso-N-acetyl penicillamine (SNAP)] or vehicle (isotonic saline) and,
      20 min after, they received a second I.C.V. injection of Ang II or vehicle.
      Injections of L-NAME or Ang II produced an increase in plasma levels of AVP, OT
      and ANP, a reduction in urinary volume and an increase in sodium excretion.
      Pretreatment with L-NAME enhanced the Ang II-induced increase in AVP, OT and ANP
      release, as well as the antidiuresis and natriuresis. Injection of SIN-1 or SNAP
      did not modify hormonal plasma levels and urinary parameters. In contrast SNAP
      blocked the AVP, OT and ANP release, as well as antidiuretic and natriuretic
      responses induced by ANG-II. Thus, the central nitrergic system can act to
      inhibit AVP, OT and ANP secretion and the antidiuretic and natriuretic effects in
      response to Ang II.

PMID- 17513346
TI  - 'Ethnic cleansing' bleaches the atrocities of genocide.
AB  - Genocide has been the leading cause of preventable violent death in the 20th-21st
      century, taking even more lives than war. The term 'ethnic cleansing' is used as
      a euphemism for genocide despite it having no legal status. Like 'Judenrein' and
      'racial hygiene' in Nazi medicine, it expropriates pseudo-medical terminology to
      justify massacre. Use of the term reifies a dehumanized view of the victims as
      sources of filth and disease, and propagates the reversed social ethics of the
      perpetrators. Timelines for recent genocides (Bosnia, 1991-1996, 200,000; Kosovo
      1998-2000, 10,000-20,000; Rwanda, 1994, 800,000; Darfur 2002-2006, >400,000) show
      that its use bears no relationship to death tolls or the scale of atrocity.
      Bystanders' use of the term 'ethnic cleansing' signals the lack of will to stop
      genocide, resulting in huge increases in deaths, and undermines international
      legal obligations to acknowledge genocide. The term 'ethnic cleansing' corrupts
      observation, interpretation, ethical judgment and decision-making, thereby
      undermining the aim of public health. Public health should lead the way in
      expunging the term 'ethnic cleansing' from official use. 'Ethnic cleansing'
      bleaches the atrocities of genocide, leading to inaction in preventing current
      and future genocides.

PMID- 17513347
TI  - Tuning a potassium channel--the caress of the surroundings.

PMID- 17513348
TI  - Tuning ion coordination architectures to enable selective partitioning.
AB  - K+ ions seemingly permeate K-channels rapidly because channel binding sites mimic
      coordination of K+ ions in water. Highly selective ion discrimination should
      occur when binding sites form rigid cavities that match K+, but not the smaller
      Na+, ion size or when binding sites are composed of specific chemical groups.
      Although conceptually attractive, these views cannot account for critical
      observations: 1), K+ hydration structures differ markedly from channel binding
      sites; 2), channel thermal fluctuations can obscure sub-Angstrom differences in
      ion sizes; and 3), chemically identical binding sites can exhibit diverse ion
      selectivities. Our quantum mechanical studies lead to a novel paradigm that
      reconciles these observations. We find that K-channels utilize a "phase
      activated" mechanism where the local environment around the binding sites is
      tuned to sustain high coordination numbers (>6) around K+ ions, which otherwise
      are rarely observed in liquid water. When combined with the field strength of
      carbonyl ligands, such high coordinations create the electrical scenario
      necessary for rapid and selective K+ partitioning. Specific perturbations to the
      local binding site environment with respect to strongly selective K-channels
      result in altered K+/Na+ selectivities.

PMID- 17513349
TI  - Quartz crystal microbalance studies of multilayer glucagon fibrillation at the
      solid-liquid interface.
AB  - We have used a quartz crystal microbalance with dissipation (QCM-D) to monitor
      the changes in layer thickness and viscoelastic properties accompanying
      multilayer amyloid deposition in situ for the first time. By means of atomic
      force microscope imaging, an unequivocal correlation is established between the
      interfacial nucleation and growth of glucagon fibrils and the QCM-D response. The
      combination of the two techniques allows us to study the temporal evolution of
      the interfacial fibrillation process. We have modeled the QCM-D data using an
      extension to the Kelvin-Voigt viscoelastic model. Three phases were observed in
      the fibrillation process: 1), a rigid multilayer of glucagon monomers forms and
      slowly rearranges; 2), this multilayer subsequently evolves into a dramatically
      more viscoelastic layer, containing a polymorphic network of micrometer-long
      fibrils growing from multiple nucleation sites; and 3), the fibrillar formation
      effectively stops as a result of the depletion of bulk-phase monomers, although
      the process can be continued without a lag phase by subsequent addition of fresh
      monomers. The robustness of the QCM-D technique, consolidated by complementary
      atomic force microscope studies, should make it possible to combine different
      components thought to be involved in the plaque formation process and thus build
      up realistic models of amyloid plaque formation in vitro.

PMID- 17513350
TI  - Quantum mechanics/molecular mechanics calculation of the Raman spectra of the
      phycocyanobilin chromophore in alpha-C-phycocyanin.
AB  - We have established a quantum mechanics (QM)/molecular mechanics (MM) hybrid
      method for calculating the Raman spectra of protein-bound cofactors using the
      alpha-subunit of C-phycocyanin containing a phycocyanobilin (PCB) chromophore as
      a test case. The PCB cofactor was described with density functional theory,
      whereas the protein matrix was treated with the CHARMM force field. The Hessian
      matrix of the QM region was built by taking into account bonded and nonbonded
      interactions with the protein environment and projected onto the internal
      coordinate space. Force constants were scaled with a global set of scaling
      factors, and the Raman intensities were computed using a finite-field method
      combined with a fourth-order differentiation algorithm for the calculation of the
      polarizability derivatives. In general, the QM/MM results provided a
      substantially improved description of the experimental resonance Raman (RR)
      spectra of the protein-bound cofactor compared to QM calculations of isolated PCB
      models in vacuo. The results allow the assessment of the effect of the protein
      cofactor interactions on the RR spectra and reveal the potential and limitations
      of QM calculations on isolated tetrapyrroles for determining the chromophore
      structures in the various species and states of phytochromes for which three
      dimensional structures are not available.

PMID- 17513351
TI  - Role of intramolecular disulfides in stability and structure of a noncovalent
      homodimer.
AB  - The importance of intramolecular disulfides in a noncovalent dimeric protein
      interleukin-8 (IL-8) has been studied by replacing cysteines in each of the two
      disulfide pairs with alpha-aminobutyric acid (CH(2)-SH --> CH(2)-CH(3)). Both
      disulfide mutants are less stable and exist as molten globules in the monomeric
      state. Interestingly, both mutants dimerize, though with slightly lower
      affinities compared to the native protein. NMR studies suggest a molten globule
      like structure also in the dimeric state. Structures, sequence analysis, and
      mutagenesis studies have shown that the conserved hydrophobic residues are packed
      against each other in the protein core and that H bonding and van der Waals
      interactions stabilize the dimer interface. Deleting either disulfide in IL-8
      results in substantial loss in receptor activity, indicating that both disulfides
      are critical for function in the folded protein. These data together suggest that
      the packing interactions of the hydrophobic core determine IL-8 monomer fold,
      that disulfides play only a marginal role in dimer formation, and that the
      stability imparted by the disulfides is intimately coupled to fold and function.

PMID- 17513352
TI  - Nanometer-sized diamond particle as a probe for biolabeling.
AB  - A novel method is proposed using nanometer-sized diamond particles as detection
      probes for biolabeling. The advantages of nanodiamond's unique properties were
      demonstrated in its biocompatibility, nontoxicity, easily detected Raman signal,
      and intrinsic fluorescence from its natural defects without complicated
      pretreatments. Carboxylated nanodiamond's (cND's) penetration ability,
      noncytotoxicity, and visualization of cND-cell interactions are demonstrated on
      A549 human lung epithelial cells. Protein-targeted cell interaction visualization
      was demonstrated with cND-lysozyme complex interaction with bacteria Escherichia
      coli. It is shown that the developed biomolecule-cND complex preserves the
      original functions of the test protein. The easily detected natural fluorescent
      and Raman intrinsic signals, penetration ability, and low cytotoxicity of cNDs
      render them promising agents in multiple medical applications.

PMID- 17513353
TI  - Spontaneous conformational changes in the E. coli GroEL subunit from all-atom
      molecular dynamics simulations.
AB  - The Escherichia coli chaperonin GroEL is a complex of identical subunit proteins
      (57 kDa each) arranged in a back-to-back stacking of two heptameric rings. Its
      hallmarks include nested positive intra-ring and negative inter-ring
      cooperativity in adenosine trisphosphate (ATP) binding and the ability to mediate
      the folding of newly transcribed and/or denatured substrate proteins. We
      performed unbiased molecular dynamics simulations of the GroEL subunit protein in
      explicit water both with and without the nucleotide KMgATP to understand better
      the details of the structural transitions that enable these behaviors. Placing
      KMgATP in the equatorial domain binding pocket of a t state subunit, which
      corresponds to a low ATP-affinity state, produced a short-lived (6 ns) state that
      spontaneously transitioned to the high ATP-affinity r state. The important
      feature of this transition is a large-scale rotation of the intermediate domain's
      helix M to close the ATP binding pocket. Pivoting of helix M is accompanied by
      counterclockwise rotation and slight deformation of the apical domain, important
      for lowering the affinity for substrate protein. Aligning simulation
      conformations into model heptamer rings demonstrates that the t-->r transition in
      one subunit is not sterically hindered by t state neighbors, but requires
      breakage of Arg(197)-Glu(386) intersubunit salt bridges, which are important for
      inter-ring positive cooperativity. Lowest-frequency quasi-harmonic modes of
      vibration computed pre- and post-transition clearly show that natural vibrations
      facilitate the transition. Finally, we propose a novel mechanism for inter-ring
      cooperativity in ATP binding inspired by the observation of spontaneous insertion
      of the side chain of Ala(480) into the empty nucleotide pocket.

PMID- 17513354
TI  - Mathematical and computational analysis of adaptation via feedback inhibition in
      signal transduction pathways.
AB  - We perform a systematic analysis of mechanisms of feedback regulation that
      underlie short-term adaptation in intracellular signaling systems. Upon receiving
      an external cue, these systems generate a transient response that quickly returns
      to basal levels even if the stimulus persists. Signaling pathways capable of
      short-term adaptation are found in systems as diverse as the high osmolarity
      response of yeast, gradient sensing in Dictyostelium, and the cytokine response
      in vertebrates. Using mathematical analysis and computational experiments, we
      compare different feedback architectures in terms of response amplitude and
      duration, ability to adapt, and response to variable stimulus levels. Our
      analysis reveals three important features of these systems: 1), multiple step
      signaling cascades improve sensitivity to low doses by an effect distinct from
      signal amplification; 2), some feedback architectures act as signal transducers
      converting stimulus strength into response duration; and 3), feedback
      deactivation acts as a dose-dependent switch between transient and sustained
      responses. Finally, we present characteristic features for each form of feedback
      regulation that can aid in their identification.

PMID- 17513355
TI  - Effect of the ionic strength and pH on the equilibrium structure of a
      neurofilament brush.
AB  - Using the numerical model of Scheutjens and Fleer, we investigated, on a self
      consistent field level, the equilibrium structure of the neurofilament brush
      formed by projection domains of the constituent NF-H, NF-M, and NF-L proteins.
      The phosphorylation of such a brush is a major regulatory process that triggers
      the relocation of the H tails from the NF core to the brush periphery. We explore
      how the pH and the ionic strength affect the rearrangements in the NF brush
      structure upon phosphorylation. We demonstrate that the translocation of H tails
      in an individual NF occurs as a sharp cooperative transition below and up to the
      physiological salt concentration. Regularities of this process are reminiscent of
      the collapse-to-stretching transition in a cylindrical polyelectrolyte brush in a
      poor solvent. The effect of pH at physiological ionic strength is noticeable only
      in the acidic range and is more pronounced for a dephosphorylated NF.

PMID- 17513356
TI  - A self-consistent field analysis of the neurofilament brush with amino-acid
      resolution.
AB  - Using the numerical model of Scheutjens and Fleer we investigated, on a self
      consistent field level, the equilibrium structure of the neurofilament brush
      formed by the projection domains of NF-H, NF-M, and NF-L proteins. Although the
      actual amino-acid sequences in the projection domains are coarse-grained, the
      different (realistic) solubilities of amino-acid residues and the specific
      distribution of its intrinsic charges inside the arms of the NF proteins are
      taken explicitly into account. We collect strong evidence that the electrostatic
      interactions are a dominant force that controls the NF brush structure. There
      exists a remarkable spatial separation of the H, M, and L tails. In a
      dephosphorylated NF we found confined and flowerlike conformations for the H and
      M projection domains, respectively. We demonstrate that the ionization of KSP
      repeats in NF proteins triggers a conformational transition in the H tail that
      leads to the expulsion of its terminal (KEP) domain to the periphery of the NF
      brush. We argue that the phosphorylation of the NF proteins in axons can both
      increase the interfilament distance and stabilize cross bridges between
      neurofilaments.

PMID- 17513357
TI  - Microscopic diffusion and hydrodynamic interactions of hemoglobin in red blood
      cells.
AB  - The cytoplasm of red blood cells is congested with the oxygen storage protein
      hemoglobin occupying a quarter of the cell volume. The high protein concentration
      leads to a reduced mobility; the self-diffusion coefficient of hemoglobin in
      blood cells is six times lower than in dilute solution. This effect is generally
      assigned to excluded volume effects in crowded media. However, the collective or
      gradient diffusion coefficient of hemoglobin is only weakly dependent on
      concentration, suggesting the compensation of osmotic and friction forces. This
      would exclude hydrodynamic interactions, which are of dynamic origin and do not
      contribute to the osmotic pressure. Hydrodynamic coupling between protein
      molecules is dominant at short time- and length scales before direct interactions
      are fully established. Employing neutron spin-echo-spectroscopy, we study
      hemoglobin diffusion on a nanosecond timescale and protein displacements on the
      scale of a few nanometers. A time- and wave-vector dependent diffusion
      coefficient is found, suggesting the crossover of self- and collective diffusion.
      Moreover, a wave-vector dependent friction function is derived, which is a
      characteristic feature of hydrodynamic interactions. The wave-vector and
      concentration dependence of the long-time self-diffusion coefficient of
      hemoglobin agree qualitatively with theoretical results on hydrodynamics in hard
      spheres suspensions. Quantitative agreement requires us to adjust the volume
      fraction by including part of the hydration shell: Proteins exhibit a larger
      surface/volume ratio compared to standard colloids of much larger size. It is
      concluded that hydrodynamic and not direct interactions dominate long-range
      molecular transport at high concentration.

PMID- 17513358
TI  - The mechanism of water transport in Na+-coupled glucose transporters expressed in
      Xenopus oocytes.

PMID- 17513359
TI  - "Nanosized voltmeter" enables cellular-wide electric field mapping.
AB  - Previously, all biological measurements of intracellular electric fields (E
      fields), using voltage dyes or patch/voltage clamps, were confined to cellular
      membranes, which account for <0.1% of the total cellular volume. These membrane
      dependent techniques also frequently require lengthy calibration steps for each
      cell or cell type measured. A new 30-nm "photonic voltmeter", 1000-fold smaller
      than existing voltmeters, enables, to our knowledge, the first complete three
      dimensional E field profiling throughout the entire volume of living cells. These
      nanodevices are calibrated externally and then applied for E field determinations
      inside any live cell or cellular compartment, with no further calibration steps.
      The results indicate that the E fields from the mitochondrial membranes penetrate
      much deeper into the cytosol than previously estimated, indicating that,
      electrically, the cytoplasm cannot be described as a simple homogeneous solution,
      as often approximated, but should rather be thought of as a complex,
      heterogeneous hydrogel, with distinct microdomains.

PMID- 17513360
TI  - Temperature-dependent folding pathways of Pin1 WW domain: an all-atom molecular
      dynamics simulation of a Go model.
AB  - We study the folding thermodynamics and kinetics of the Pin1 WW domain, a three
      stranded beta-sheet protein, by using all-atom (except nonpolar hydrogens)
      discontinuous molecular dynamics simulations at various temperatures with a Go
      model. The protein exhibits a two-state folding kinetics near the folding
      transition temperature. A good agreement between our simulations and the
      experimental measurements by the Gruebele group has been found, and the
      simulation sheds new insights into the structure of transition state, which is
      hard to be straightforwardly captured in experiments. The simulation also reveals
      that the folding pathways at approximately the transition temperature and at low
      temperatures are much different, and an intermediate state at a low temperature
      is predicted. The transition state of this small beta-protein at its folding
      transition temperature has a well-established hairpin 1 made of beta1 and beta2
      strands while its low-temperature kinetic intermediate has a formed hairpin 2
      composed of beta2 and beta3 strands. Theoretical results are compared with other
      simulation results as well as available experimental data. This study confirms
      that specific side-chain packing in an all-atom Go model can yield a reasonable
      prediction of specific folding kinetics for a given protein. Different folding
      behaviors at different temperatures are interpreted in terms of the interplay of
      entropy and enthalpy in folding process.

PMID- 17513361
TI  - Charge immobilization of skeletal muscle Na+ channels: role of residues in the
      inactivation linker.
AB  - We investigated structural determinants of fast inactivation and deactivation in
      sodium channels by comparing ionic flux and charge movement in skeletal muscle
      channels, using mutations of DIII-DIV linker charges. Charge altering and
      substituting mutations at K-1317, K-1318 depolarized the g(V) curve but
      hyperpolarized the h(infinity) curve. Charge reversal and substitution at this
      locus reduced the apparent voltage sensitivity of open- and closed-state fast
      inactivation. These effects were not observed with charge reversal at E-1314, E
      1315. Mutations swapping or neutralizing the negative cluster at 1314, 1315 and
      the positive cluster at 1317, 1318 indicated that local interactions dictate the
      coupling of activation to fast inactivation. Gating charge was immobilized before
      channel entry into fast inactivation in hNa(V)1.4 but to a lesser extent in
      mutations at K-1317, K-1318. These results suggest that charge is preferentially
      immobilized in channels inactivating from the open state. Recovery of gating
      charge proceeded with a single, fast phase in the double mutation K-1317R, K
      1318R. This mutation also partially uncoupled recovery from deactivation. Our
      findings indicate that charged residues near the fast inactivation "particle"
      allosterically interact with voltage sensors to control aspects of gating in
      sodium channels.

PMID- 17513362
TI  - Electrostatic and steric interactions determine bacteriorhodopsin single-molecule
      biomechanics.
AB  - Bacteriorhodopsin (bR) is a haloarchaeal membrane protein that converts the
      energy of single photons into large structural changes to directionally pump
      protons across purple membrane. This is achieved by a complex combination of
      local dynamic interactions controlling bR biomechanics at the submolecular level,
      producing efficient amplification of the retinal photoisomerization. Using single
      molecule force spectroscopy at different salt concentrations, we show that
      tryptophan (Trp) residues use steric specific interactions to create a rigid
      scaffold in bR extracellular region and are responsible for the main unfolding
      barriers. This scaffold, which encloses the retinal, controls bR local mechanical
      properties and anchors the protein into the membrane. Furthermore, the stable Trp
      based network allows ion binding to two specific sites on the extracellular loops
      (BC and FG), which are involved in proton release and lateral transport. In
      contrast, the cytoplasmic side of bR is mainly governed by relatively weak
      nonspecific electrostatic interactions that provide the flexibility necessary for
      large cytoplasmic structural rearrangements during the photocycle. The presence
      of an extracellular Trp-based network tightly enclosing the retinal seems common
      to most haloarchaeal rhodopsins, and could be relevant to their exceptional
      efficiency.

PMID- 17513363
TI  - Kinetics of complexin binding to the SNARE complex: correcting single molecule
      FRET measurements for hidden events.
AB  - Virtually all measurements of biochemical kinetics have been derived from
      macroscopic measurements. Single-molecule methods can reveal the kinetic behavior
      of individual molecular complexes and thus have the potential to determine
      heterogeneous behaviors. Here we have used single-molecule fluorescence resonance
      energy transfer to determine the kinetics of binding of SNARE (soluble N-ethyl
      maleimide-sensitive fusion protein attachment protein receptor) complexes to
      complexin and to a peptide derived from the central SNARE binding region of
      complexin. A Markov model was developed to account for the presence of unlabeled
      competitor in such measurements. We find that complexin associates rapidly with
      SNARE complexes anchored in lipid bilayers with a rate constant of 7.0 x 10(6) M(
      1) s(-1) and dissociates slowly with a rate constant of 0.3 s(-1). The complexin
      peptide associates with SNARE complexes at a rate slower than that of full-length
      complexin (1.2 x 10(6) M(-1) s(-1)), and dissociates much more rapidly (rate
      constant >67 s(-1)). Comparison of single-molecule fluorescence resonance energy
      transfer measurements made using several dye attachment sites illustrates that
      dye labeling of complexin can modify its rate of unbinding from SNAREs. These
      rate constants provide a quantitative framework for modeling of the cascade of
      reactions underlying exocytosis. In addition, our theoretical correction
      establishes a general approach for improving single-molecule measurements of
      intermolecular binding kinetics.

PMID- 17513364
TI  - The chloroplast Tat pathway utilizes the transmembrane electric potential as an
      energy source.
AB  - The thylakoid membrane, located inside the chloroplast, requires proteins
      transported across it for plastid biogenesis and functional photosynthetic
      electron transport. The chloroplast Tat translocator found on thylakoids
      transports proteins from the plastid stroma to the thylakoid lumen. Previous
      studies have shown that the chloroplast Tat pathway is independent of NTP
      hydrolysis as an energy source and instead depends on the thylakoid transmembrane
      proton gradient to power protein translocation. Because of its localization on
      the same membrane as the proton motive force-dependent F(0)F(1) ATPase, we
      believed that the chloroplast Tat pathway also made use of the thylakoid electric
      potential for transporting substrates. By adjusting the rate of photosynthetic
      proton pumping and by utilizing ionophores, we show that the chloroplast Tat
      pathway can also utilize the transmembrane electric potential for protein
      transport. Our findings indicate that the chloroplast Tat pathway is likely
      dependent on the total protonmotive force (PMF) as an energy source. As a
      protonmotive-dependent device, certain predictions can be made about structural
      features expected to be found in the Tat translocon, specifically, the presence
      of a proton well, a device in the membrane that converts electrical potential
      into chemical potential.

PMID- 17513365
TI  - Extracellular proton-modulated pore-blocking effect of the anticonvulsant
      felbamate on NMDA channels.
AB  - Felbamate (FBM) is a potent nonsedative anticonvulsant whose clinical effect is
      chiefly related to gating modification (and thus use-dependent inhibition) rather
      than pore block of N-methyl-D-aspartate (NMDA) channels at pH 7.4. Using whole
      cell recording in rat hippocampal neurons, we examined the effect of
      extracellular pH on FBM action. In sharp contrast to the findings at pH 7.4, the
      inhibitory effect of FBM on NMDA currents shows much weakened use-dependence at
      pH 8.4. Moreover, FBM neither accelerates the activation kinetics of the NMDA
      channel, nor enhances the currents elicited by very low concentrations of NMDA at
      pH 8.4. These differential effects of FBM between pH 7.4 and 8.4 are abolished in
      the mutant NMDA channels which lack proton sensitivity. Most interestingly, the
      inhibitory effect of FBM becomes flow-dependent and is evidently stronger in
      inward than in outward NMDA currents at pH 8.4. These findings indicate that FBM
      has a significantly more manifest pore-blocking effect on the NMDA channel at pH
      8.4 than at pH 7.4. FBM therefore acts as an opportunistic pore blocker modulated
      by extracellular proton, suggesting that the FBM binding site is located at the
      junction of a widened and a narrow part of the ion conduction pathway. Also, we
      find that the inhibitory effect of FBM on NMDA currents is antagonized by
      external but not internal Na+, and that increase of external Na+ decreases the
      binding rate without altering the unbinding rate of FBM. These findings indicate
      that the FBM binding site faces the extracellular rather than the intracellular
      solution, and coincides with the outmost ionic (e.g., Na+) site in the NMDA
      channel pore. We conclude that the FBM binding site very likely is located in the
      external pore mouth, where extracellular proton, Na+, FBM, and NMDA channel
      gating have an orchestrating effect.

PMID- 17513366
TI  - Solvation effect of bacteriochlorophyll excitons in light-harvesting complex LH2.
AB  - We have characterized the influence of the protein environment on the spectral
      properties of the bacteriochlorophyll (Bchl) molecules of the peripheral light
      harvesting (or LH2) complex from Rhodobacter sphaeroides. The spectral density
      functions of the pigments responsible for the 800 and 850 nm electronic
      transitions were determined from the temperature dependence of the Bchl
      absorption spectra in different environments (detergent micelles and native
      membranes). The spectral density function is virtually independent of the
      hydrophobic support that the protein experiences. The reorganization energy for
      the B850 Bchls is 220 cm(-1), which is almost twice that of the B800 Bchls, and
      its Huang-Rhys factor reaches 8.4. Around the transition point temperature, and
      at higher temperatures, both the static spectral inhomogeneity and the resonance
      interactions become temperature-dependent. The inhomogeneous distribution
      function of the transitions exhibits less temperature dependence when LH2 is
      embedded in membranes, suggesting that the lipid phase protects the protein.
      However, the temperature dependence of the fluorescence spectra of LH2 cannot be
      fitted using the same parameters determined from the analysis of the absorption
      spectra. Correct fitting requires the lowest exciton states to be additionally
      shifted to the red, suggesting the reorganization of the exciton spectrum.

PMID- 17513367
TI  - Dynamics of firefly luciferase inhibition by general anesthetics: Gaussian and
      anisotropic network analyses.
AB  - The new crystal structures of the product-bound firefly luciferase combined with
      the previously determined substrate-free structures allow for a detailed analysis
      of the dynamics basis for the luciferase enzymatic activities. Using the Gaussian
      network model and the anisotropic network model, we show here that the
      superposition of the three slowest anisotropic network model modes, consisting of
      the bending, rotating, and rocking motions of the C-domain, accounts for large
      rearrangement of domains from the substrate-free (open) to product-bound (closed)
      conformation and thus constitutes a critical component of the enzyme's functions.
      The analysis also offers a unique platform to reexamine the molecular mechanism
      of the anesthetic inhibition of the firefly luciferase. Through perturbing the
      protein backbone network by introducing additional nodes to represent
      anesthetics, we found that the presence of two representative anesthetics,
      halothane and n-decanol, in different regions of luciferase had distinctively
      different effects on the protein's global motion. Only at the interface of the C-
      and N-domains did the anesthetics cause the most profound reduction in the
      overall flexibility of the C-domain and the concomitant increase in the
      flexibility of the loop, where the substitution of a conserved lysine residue was
      found experimentally to lead to >2-3 orders of magnitude reduction in activity.
      These anesthetic-induced dynamics changes can alter the normal function of the
      protein, appearing as an epiphenomenon of an "inhibition". The implication of the
      study is that a leading element for general anesthetic action on proteins is to
      disrupt the modes of motion essential to protein functions.

PMID- 17513368
TI  - A mechanical explanation for cytoskeletal rings and helices in bacteria.
AB  - Several bacterial proteins have been shown to polymerize into coils or rings on
      cell membranes. These include the cytoskeletal proteins MreB, FtsZ, and MinD,
      which together with other cell components make up what is being called the
      bacterial cytoskeleton. We believe that these shapes arise, at least in part,
      from the interaction of the inherent mechanical properties of the protein
      polymers and the constraints imposed by the curved cell membrane. This
      hypothesis, presented as a simple mechanical model, was tested with numerical
      energy-minimization methods from which we found that there are five low-energy
      polymer morphologies on a rod-shaped membrane: rings, lines, helices, loops, and
      polar-targeted circles. Analytic theory was used to understand the possible
      structures and to create phase diagrams that show which parameter combinations
      lead to which structures. Inverting the results, it is possible to infer the
      effective mechanical bending parameters of protein polymers from fluorescence
      images of their shapes. This theory also provides a plausible explanation for the
      morphological changes exhibited by the Z ring in a sporulating Bacillus subtilis;
      is used to calculate the mechanical force exerted on a cell membrane by a
      polymer; and allows predictions of polymer shapes in mutant cells.

PMID- 17513369
TI  - Structure and plasticity of the human immunodeficiency virus gp41 fusion domain
      in lipid micelles and bilayers.
AB  - A thorough understanding of the structure of fusion domains of enveloped viruses
      in changing lipid environments helps us to formulate mechanistic models on how
      they might function in mediating viral entry by membrane fusion. We have
      expressed the N-terminal fusion domain of HIV-1 gp41 as a construct that is water
      soluble in the absence of membranes, but that also binds with high affinity to
      lipid micelles and bilayers in their presence. We have solved the structure and
      studied the dynamics of this domain bound to dodecylphosphocholine micelles by
      homo- and heteronuclear NMR spectroscopy. The fusion peptide forms a stable
      hydrophobic helix from Ile(4) to Ala(14), but is increasingly more disordered and
      dynamic in a segment of intermediate polarity that stretches from Ala(15) to
      Ser(23). When bound to lipid bilayers at low concentration, the HIV fusion domain
      is also largely alpha-helical, as determined by CD and FTIR spectroscopy.
      However, at higher protein/lipid ratios, the domain is partially converted to
      form beta-structures in lipid bilayers. Controlled lipid mixing occurs at
      concentrations that support the alpha-helical, but not the beta-strand
      conformation.

PMID- 17513370
TI  - Chlorophyll ring deformation modulates Qy electronic energy in chlorophyll
      protein complexes and generates spectral forms.
AB  - The possibility that the chlorophyll (chl) ring distortions observed in the
      crystal structures of chl-protein complexes are involved in the transition energy
      modulation, giving rise to the spectral forms, is investigated. The out-of-plane
      chl-macrocycle distortions are described using an orthonormal set of
      deformations, defined by the displacements along the six lowest-frequency, out-of
      plane normal coordinates. The total chl-ring deformation is the linear
      combination of these six deformations. The two higher occupied and the two lower
      unoccupied chl molecular orbitals, which define the Q(y) electronic transition,
      have the same symmetry as four of the six out-of-plane lowest frequency modes. We
      assume that a deformation along the normal-coordinate having the same symmetry as
      a given molecular orbital will perturb that orbital and modify its energy. The
      changes in the chl Q(y) transition energies are evaluated in the Peridinin-Chl
      Protein complex and in light harvesting complex II (LHCII), using
      crystallographic data. The macrocycle deformations induce a distribution of the
      chl Q(y) electronic energy transitions which, for LHCII, is broader for chla than
      for chlb. This provides the physical mechanism to explain the long-held view that
      the chla spectral forms in LHCII are both more numerous and cover a wider energy
      range than those of chlb.

PMID- 17513371
TI  - Macromolecular crowding induces a molten globule state in the C-terminal domain
      of histone H1.
AB  - We studied the secondary structure of the C-terminal domains of the histone H1
      subtypes H1 degrees (C-H1 degrees ) and H1t (C-H1t) in the presence of
      macromolecular crowding agents (Ficoll 70 and PEG 6000) by IR spectroscopy. The
      carboxyl-terminal domain has little structure in aqueous solution but became
      extensively folded in the presence of crowding agents. In 30% PEG, C-H1 degrees
      contained 19% alpha-helix, 28% beta-sheet, 16% turns, and 31% open loops. Similar
      proportions were observed in 30% Ficoll 70 and for C-H1t in both crowding agents.
      The proportions of secondary structure motifs were comparable to those of the DNA
      bound domain. Kratky plots of the small-angle x-ray scattering showed that in
      crowding agents the C-terminus had the compaction of a globular state.
      Progressive dissipation of the secondary structure and a linear increase in
      partial heat capacity with temperature together with increased binding of ANS
      indicated that the C-terminus is not cooperatively folded in crowded conditions.
      Native-like secondary structure and compactness in absence of folding
      cooperativity indicate that the C-terminus in crowding agents is in a molten
      globule state. Folding of the C-terminus in crowded conditions may increase the
      rate of the transition toward the DNA-bound state and facilitate H1 diffusion
      inside cell nuclei.

PMID- 17513372
TI  - Biased random walk by stochastic fluctuations of chemoattractant-receptor
      interactions at the lower limit of detection.
AB  - Binding of ligand to its receptor is a stochastic process that exhibits
      fluctuations in time and space. In chemotaxis, this leads to a noisy input
      signal. Therefore, in a gradient of chemoattractant, the cell may occasionally
      experience a "wrong" gradient of occupied receptors. We obtained a simple
      equation for P(pos), the probability that half of the cell closest to the source
      of chemoattractant has higher receptor occupancy than the opposite half of the
      cell. P(pos) depends on four factors, the gradient property delC/sq. root of C,
      the receptor characteristic R(t)/K(D), a time-averaging constant I, and
      nonreceptor noise sigma(B). We measured chemotaxis of Dictyostelium cells to
      known shallow gradients of cAMP and obtained direct estimates for these
      constants. Furthermore, we observed that in shallow gradients, the measured
      chemotaxis index is correlated with P(pos), which suggests that chemotaxis in
      shallow gradients is a pure biased random walk. From the observed chemotaxis and
      derived time-averaging constant, we deduce that the gradient transducing second
      messenger has a lifetime of 2-8 s and a diffusion rate constant of approximately
      1 microm(2)/s. Potential candidates for such second messengers are discussed.

PMID- 17513373
TI  - A thermodynamic and structural study of myelin basic protein in lipid membrane
      models.
AB  - Myelin basic protein (MBP) is a major protein of the myelin membrane in the
      central nervous system. It is believed to play a relevant role in the structure
      and function of the myelin sheath and is a candidate autoantigen in demyelinating
      processes such as multiple sclerosis. MBP has many features typical of soluble
      proteins but is capable of strongly interacting with lipids, probably via a
      conformation change. Its structure in the lipid membrane as well as the details
      of its interaction with the lipid membrane are still to be resolved. In this
      article we study the interaction of MBP with Langmuir films of anionic and
      neutral phospholipids, used as experimental models of the lipid membrane. By
      analyzing the equilibrium surface pressure/area isotherms of these films, we
      measured the protein partition coefficient between the aqueous solution and the
      lipid membrane, the mixing ratio between protein and lipid, and the area of the
      protein molecules inserted in the lipid film. The penetration depth of MBP in the
      lipid monolayer was evaluated by x-ray reflectivity measurements. The mixing
      ratio and the MBP molecular area decrease as the surface pressure increases, and
      at high surface pressure the protein is preferentially located at the lipid/water
      interface for both anionic and neutral lipids. The morphology of MBP adsorbed on
      lipid films was studied by atomic force microscopy. MBP forms bean-like
      structures and induces a lateral compaction of the lipid surface. Scattered MBP
      particles have also been observed. These particles, which are 2.35-nm high, 4.7
      nm wide, and 13.3-nm long, could be formed by protein-lipid complexes. On the
      basis of their size, they could also be either single MBP molecules or pairs of c
      shaped interpenetrating molecules.

PMID- 17513374
TI  - Imaging and shape analysis of GUVs as model plasma membranes: effect of trans
      DOPC on membrane properties.
AB  - Unsaturated trans fatty acids have been linked to a higher incidence of coronary
      artery disease, but not enough is known about the effect of trans lipids on
      membrane properties. Liquid-ordered (l(o)) and liquid-disordered (l(d)) membrane
      domains are implicated in various biological processes, such as endocytosis,
      adhesion, signaling, protein transport, apoptosis, and disease pathogenesis. The
      physical forces that induce domain formation and thus orchestrate cell function
      need to be further addressed and quantified. Here, we test the effect of trans
      DOPC (dielaidoyl phosphatidylcholine or DEPC) on the morphology of giant
      unilamellar vesicles (GUVs, used as a biomembrane model) made by electroformation
      with varying compositions of egg sphingomyelin, trans DOPC, cis DOPC, and
      cholesterol. GUVs were imaged by confocal fluorescence microscopy and then
      analyzed for changes in membrane morphology and properties such as l(o)/l(d)
      phase coexistence and area fractions, distribution of meridional curvature, and
      fluorescent-probe intensity distribution. BODIPY-FL-C(12)-sphingomyelin,
      Lissamine rhodamine B dioleoylphosphatidylethanolamine and BODIPY-TR-C(12)
      sphingomyelin were used as fluorescent probes to differentially label the l(o)
      and l(d) phases. Trans DOPC induces some vesicles to form multidomain,
      invaginated morphologies that differ from the typical two-domain circular and
      truncated spherical shapes observed in its absence. Trans DOPC also alters the
      membrane curvature distribution; this is more pronounced in the l(o) phase near
      the phase boundary, where significantly negative curvatures (<-0.5 microm(-1))
      are observed. A narrower distribution of meridional curvatures in GUVs with trans
      DOPC is suggestive of higher membrane bending rigidity. The ratio of average
      fluorescent intensities in the l(d)/l(o) phases indicates a greater concentration
      or brightness of the probes BODIPY-FL-C(12)-sphingomyelin and BODIPY-TR-C(12)
      sphingomyelin in the l(o) phase in the presence of trans DOPC. Addition of trans
      DOPC does not alter the l(o)/l(d) area fractions, indicating that it does not act
      like egg sphingomyelin, a saturated lipid. These changes in membrane properties
      seen in the presence of trans lipids could significantly impact cell function.

PMID- 17513375
TI  - Kinetic refolding barrier of guanidinium chloride denatured goose delta
      crystallin leads to regular aggregate formation.
AB  - Delta-crystallin is the major soluble protein in avian eye lenses with a
      structural role in light scattering. Dissociation and unfolding of the tetrameric
      protein in guanidinium chloride (GdmCl) can be sensitively monitored by the
      intrinsic tryptophan fluorescence. In this study refolding of GdmCl-denatured
      delta-crystallin was investigated. A marked hysteresis was observed while
      refolding by dilution of the 5 M GdmCl-denatured delta-crystallin. The secondary
      structure of the refolded protein was largely restored. However, monitoring
      intrinsic fluorescence of single tryptophan mutants indicated that the
      microenvironment of domain 1 (W74) was not restored. The region containing W169,
      which is close to the dimer interface, remained exposed following refolding.
      During refolding of the wild-type protein, dimeric, tetrameric, and aggregate
      forms were identified. The ratio of tetramer to dimer increased with time, as
      judged by gel-filtration chromatography and nondenaturing gel electrophoresis.
      However the observed levels of tetramer did not return to the same levels as
      observed before GdmCl treatment. The proportion of tetramer was significantly
      decreased in the N-25 deletion mutant and it did not increase with time. These
      results suggest that there is a kinetic barrier for assembly of dimers into
      tetramers. The consequence of this is that dimers refold to form aggregates.
      Aggregation seems to follow a nucleation mechanism with an apparent reaction
      order of 4.7+/-0.2, suggesting four or five monomers constitute the core
      structure of nucleus, which propagate to form high molecular weight aggregates.
      Addition of alpha-crystallin during refolding prevents aggregation. Thioflavin T
      and Congo red assays indicated a regular structure for the protein aggregates,
      which appear as hollow tubules packed into helical bundles. Aggregate formation
      was protein concentration dependent that progressed via two stages with rate
      constants of 0.0039+/-0.0006 and 0.00043+/-0.00003 s(-1), respectively. We
      propose that the N-terminal segment of delta-crystallin plays a critical role in
      proper double dimer assembly and also in the assembly of nucleus to aggregate
      formation.

PMID- 17513376
TI  - GFP-tagged regulatory light chain monitors single myosin lever-arm orientation in
      a muscle fiber.
AB  - Myosin is the molecular motor in muscle-binding actin and executing a power
      stroke by rotating its lever arm through an angle of approximately 70 degrees to
      translate actin against resistive force. A green fluorescent protein (GFP)-tagged
      human cardiac myosin regulatory light chain (HCRLC) was constructed to study in
      situ lever arm orientation one molecule at a time by polarized fluorescence
      emitted from the GFP probe. The recombinant protein physically and functionally
      replaced the native RLC on myosin lever arms in the thick filaments of
      permeabilized skeletal muscle fibers. Detecting single molecules in fibers where
      myosin concentration reaches 300 microM is accomplished using total internal
      reflection fluorescence microscopy. With total internal reflection fluorescence,
      evanescent field excitation, supercritical angle fluorescence detection, and CCD
      detector pixel size limits detection volume to just a few attoliters. Data
      analysis manages both the perturbing effect of the TIR interface on probe
      emission and the effect of high numerical aperture collection of light. The
      natural myosin concentration gradient in a muscle fiber allows observation of
      fluorescence polarization from C-term GFP-tagged HCRLC exchanged myosin from
      regions in the thick filament containing low and high myosin concentrations. In
      rigor, cross-bridges at low concentration at the end of the thick filament
      maintain GFP dipole moments at two distinct polar angles relative to the fiber
      symmetry axis. The lower angle, where the dipole is nearly parallel to fiber
      axis, is more highly populated than the alternative, larger angle. Cross-bridges
      at higher concentration in the center of the thick filament are oriented in a
      homogeneous band at approximately 45 degrees to the fiber axis. The data suggests
      molecular crowding impacts myosin conformation, implying mutual interactions
      between cross-bridges alter how the muscle generates force. The GFP-tagged RLC is
      a novel probe to assess single-lever-arm orientation characteristics in situ.

PMID- 17513377
TI  - Polymer properties of polythymine as revealed by translational diffusion.
AB  - Biopolymers, such as single-stranded DNA (ssDNA), are often described as
      semiflexible polymers or wormlike chains. We investigated the length dependence
      of diffusional properties of homogeneous ssDNA (polythymine) with up to 100
      nucleotides using fluorescence correlation spectroscopy. We found that the
      hydrodynamic radius Rh scales according to a power law, with an exponent between
      0.5 and 0.7 depending on ionic strength I. With Rh being proportional to the
      square root of the persistence length Lp, we found that Lp approximately Im, with
      m=-0.22+/-0.01 for polythymine with 100 residues. For comparison, we performed
      molecular dynamics (MD) simulations with a force field that accounts for short
      range interactions in vacuum, and determined the characteristic polymer
      properties end-to-end distance R, radius of gyration S, and persistence length Lp
      of various labeled and nonlabeled polythymine derivatives. We found excellent
      agreement for the length dependence of simulated S and experimental Rh measured
      at 100 mM NaCl, revealing that electrostatic interactions are completely shielded
      in aqueous solution at such ionic strength. MD simulations further showed that
      polythymine with >approximately 30 residues can be described as a semiflexible
      polymer with negligible influence of the fluorescent label; and that static
      flexibility is limited by geometrical and steric constraints as expressed by an
      intrinsic persistence length of approximately 1.7 nm. These results provide a
      benchmark for theories and MD simulations describing the influence of
      electrostatic interactions on polyelectrolyte properties, and thus help to
      develop a complete and accurate description of ssDNA.

PMID- 17513378
TI  - Solubility versus electrostatics: what determines lipid/protein interaction in
      lung surfactant.
AB  - Mammalian lung surfactant is a complex lipid/protein mixture covering the
      alveolar interface and has the crucial function of reducing the surface tension
      at this boundary to minimal values. Surfactant protein SP-B plays an important
      role for this purpose and was the focus of many recent studies. However, the
      specificity of lipid/SP-B interactions is controversial. Since these
      investigations were accomplished at varying pH conditions (pH 5.5 and 7.0), we
      studied the specificity of these interactions in a dipalmitoylphosphatidylcholine
      (DPPC)/dipalmitoylphosphatidylglycerol (DPPG)/SP-B (4:1:0.2 mol %) model system
      at either pH. Mainly fluorescence microscopy and laterally resolved time-of
      flight secondary ion mass spectrometry were used to reveal information about the
      phase behavior of the lipids and the molecular distribution of SP-B in the lipid
      mixture. DPPG forms separated condensed domains due to a strong hydrogen-bond
      network, from which the protein is mainly excluded. Considering the protein as an
      impurity of the lipid mixture leads to the principle of the zone melting process:
      an impurity is highly more soluble in a liquid phase than in a solid phase. The
      phase behavior effect of the lipids mainly outperforms the electrostatic
      interactions between DPPG and SP-B, leading to a more passively achieved
      colocalization of DPPC and SP-B.

PMID- 17513379
TI  - Stochastic entry of enveloped viruses: fusion versus endocytosis.
AB  - Infection by membrane-enveloped viruses requires the binding of receptors on the
      target cell membrane to glycoproteins, or "spikes," on the viral membrane. The
      initial entry mechanism is usually classified as fusogenic or endocytotic.
      However, binding of viral spikes to cell surface receptors not only initiates the
      viral adhesion and the wrapping process necessary for internalization, but can
      simultaneously initiate direct fusion with the cell membrane. Both fusion and
      internalization have been observed to be viable pathways for many viruses. We
      develop a stochastic model for viral entry that incorporates a competition
      between receptor-mediated fusion and endocytosis. The relative probabilities of
      fusion and endocytosis of a virus particle initially nonspecifically adsorbed on
      the host cell membrane are computed as functions of receptor concentration,
      binding strength, and number of spikes. We find different parameter regimes where
      the entry pathway probabilities can be analytically expressed. Experimental tests
      of our mechanistic hypotheses are proposed and discussed.

PMID- 17513380
TI  - Two-color fluorescence analysis of individual virions determines the distribution
      of the copy number of proteins in herpes simplex virus particles.
AB  - We present a single virion method to determine absolute distributions of copy
      number in the protein composition of viruses and apply it to herpes simplex virus
      type 1. Using two-color coincidence fluorescence spectroscopy, we determine the
      virion-to-virion variability in copy numbers of fluorescently labeled tegument
      and envelope proteins relative to a capsid protein by analyzing fluorescence
      intensity ratios for ensembles of individual dual-labeled virions and fitting the
      resulting histogram of ratios. Using EYFP-tagged capsid protein VP26 as a
      reference for fluorescence intensity, we are able to calculate the mean and also,
      for the first time to our knowledge, the variation in numbers of gD, VP16, and
      VP22 tegument. The measurement of the number of glycoprotein D molecules was in
      good agreement with independent measurements of average numbers of these
      glycoproteins in bulk virus preparations, validating the method. The accuracy,
      straightforward data processing, and high throughput of this technique make it
      widely applicable to the analysis of the molecular composition of large complexes
      in general, and it is particularly suited to providing insights into virus
      structure, assembly, and infectivity.

PMID- 17513381
TI  - Interaction forces between F-actin and titin PEVK domain measured with optical
      tweezers.
AB  - Titin is a giant protein that determines the elasticity of striated muscle and is
      thought to play important roles in numerous regulatory processes. Previous
      studies have shown that titin's PEVK domain interacts with F-actin, thereby
      creating viscous forces of unknown magnitude that may modulate muscle
      contraction. Here we measured, with optical tweezers, the forces necessary to
      dissociate F-actin from individual molecules of recombinant PEVK fragments rich
      either in polyE or PPAK motifs. Rupture forces at a stretch rate of 250 nm/s
      displayed a wide, nonnormal distribution with a peak at approximately 8 pN in the
      case of both fragments. Dynamic force spectroscopy experiments revealed low
      spontaneous off-rates that were increased even by low forces. The loading-rate
      dependence of rupture force was biphasic for polyE in contrast with the
      monophasic response observed for PPAK. Analysis of the molecular lengths at which
      rupture occurred indicated that there are numerous actin-binding regions along
      the PEVK fragments' contour, suggesting that the PEVK domain is a promiscuous
      actin-binding partner. The complexity of PEVK-actin interaction points to an
      adaptable viscoelastic mechanism that safeguards sarcomeric structural integrity
      in the relaxed state and modulates thixotropic behavior during contraction.

PMID- 17513382
TI  - Conformational dynamics of the alphaM3 transmembrane helix during acetylcholine
      receptor channel gating.
AB  - Muscle acetylcholine receptors are synaptic ion channels that "gate" between
      closed- and open-channel conformations. We used Phi-value analysis to probe the
      transition state of the diliganded gating reaction with regard to residues in the
      M3, membrane-spanning helix of the muscle acetylcholine receptor alpha-subunit.
      Phi (a fraction between 1 and 0) parameterizes the extent to which a mutation
      changes the opening versus the closing rate constant and, for a linear reaction
      mechanism, the higher the Phi-value, the "earlier" the gating motion. In the
      upper half of alphaM3 the gating motions of all five tested residues were
      temporally correlated (Phi approximately 0.30) and serve to link structural
      changes occurring at the middle of the M2, pore-lining helix with those occurring
      at the interface of the extracellular and transmembrane domains. alphaM3 belongs
      to a complex and diverse set of synchronously moving parts that change structure
      relatively late in the channel-opening process. The propagation of the gating
      Brownian conformational cascade has a complex spatial distribution in the
      transmembrane domain.

PMID- 17513384
TI  - Effects of macromolecular crowding on biochemical reaction equilibria: a
      molecular thermodynamic perspective.
AB  - A molecular thermodynamic model is developed to investigate the effects of
      macromolecular crowding on biochemical reactions. Three types of reactions,
      representing protein folding/conformational isomerization,
      coagulation/coalescence, and polymerization/association, are considered. The
      reactants, products, and crowders are modeled as coarse-grained spherical
      particles or as polymer chains, interacting through hard-sphere interactions with
      or without nonbonded square-well interactions, and the effects of crowder size
      and chain length as well as product size are examined. The results predicted by
      this model are consistent with experimentally observed crowding effects based on
      preferential binding or preferential exclusion of the crowders. Although simple
      hard-core excluded-volume arguments do in general predict the qualitative aspects
      of the crowding effects, the results show that other intermolecular interactions
      can substantially alter the extent of enhancement or reduction of the equilibrium
      and can even change the direction of the shift. An advantage of the approach
      presented here is that competing reactions can be incorporated within the model.

PMID- 17513383
TI  - The permeability enhancing mechanism of DMSO in ceramide bilayers simulated by
      molecular dynamics.
AB  - The lipids of the topmost layer of the skin, the stratum corneum, represent the
      primary barrier to molecules penetrating the skin. One approach to overcoming
      this barrier for the purpose of delivery of active molecules into or via the skin
      is to employ chemical permeability enhancers, such as dimethylsulfoxide (DMSO).
      How these molecules exert their effect at the molecular level is not understood.
      We have investigated the interaction of DMSO with gel-phase bilayers of ceramide
      2, the predominant lipid in the stratum corneum, by means of molecular dynamics
      simulations. The simulations satisfactorily reproduce the phase behavior and the
      known structural parameters of ceramide 2 bilayers in water. The effect of DMSO
      on the gel-phase bilayers was investigated at various concentrations over the
      range 0.0-0.6 mol fraction DMSO. The DMSO molecules accumulate in the headgroup
      region and weaken the lateral forces between the ceramides. At high
      concentrations of DMSO (> or =0.4 mol fraction), the ceramide bilayers undergo a
      phase transition from the gel phase to the liquid crystalline phase. The liquid
      crystalline phase of ceramides is expected to be markedly more permeable to
      solutes than the gel phase. The results are consistent with the experimental
      evidence that high concentrations of DMSO fluidize the stratum corneum lipids and
      enhance permeability.

PMID- 17513385
TI  - Inhibition of hypoxia-induced increase of blood-brain barrier permeability by YC
      1 through the antagonism of HIF-1alpha accumulation and VEGF expression.
AB  - Cerebral microvascular endothelial cells form the anatomical basis of the blood
      brain barrier (BBB), and the tight junctions of the BBB are critical for
      maintaining brain homeostasis and low permeability. Ischemia/reperfusion is known
      to damage the tight junctions of BBB and lead to permeability changes. Here we
      investigated the protective role of 3-(5'-hydroxymethyl-2'-furyl)-1
      benzylindazole (YC-1), against chemical hypoxia and hypoxia/reoxygenation (H/R)
      induced BBB hyperpermeability using adult rat brain endothelial cell culture
      (ARBEC). YC-1 significantly decreased CoCl2- and H/R-induced hyperpermeability of
      fluorescein isothiocyanate (FITC)-dextran in cell culture inserts. It was found
      that the decrease and disorganization of tight junction protein zonular occludens
      1 (ZO-1) in response to CoCl2, and H/R was antagonized by YC-1. The protection of
      YC-1 may result from the inhibition of HIF-1alpha accumulation and production of
      its downstream target vascular endothelial growth factor (VEGF). VEGF alone
      significantly increased FITC-dextran permeability and down-regulated mRNA and
      protein levels of ZO-1 in ARBECs. We further used animal model to examine the
      effect of YC-1 on BBB permeability after cerebral ischemia/reperfusion. It was
      found that YC-1 significantly protected the BBB against ischemia/reperfusion
      induced injury. Taken together, these results indicate that YC-1 may inhibit HIF
      1alpha accumulation and VEGF production, which in turn protect BBB from injury
      caused by hypoxia.

PMID- 17513387
TI  - Defining occupational asthma and confirming the diagnosis: what do experts
      suggest?

PMID- 17513388
TI  - Urban pest control operators in Australia.

PMID- 17513389
TI  - Injustice at work and health: causation, correlation or cause for action?

PMID- 17513390
TI  - David Kritchevsky (1920-2006).

PMID- 17513391
TI  - Glutamine directly downregulates glutamine synthetase protein levels in mouse
      C2C12 skeletal muscle myotubes.
AB  - This study examined the regulation of glutamine synthetase protein levels, in
      response to changes in external glutamine concentration, in mouse C2C12 skeletal
      muscle cells. Glutamine, at concentrations as low as 0.25 mmol/L, downregulated
      endogenous and exogenous (plasmid encoded) glutamine synthetase with maximal
      effect at 2 mmol/L. Glutamine appears to act by changing the stability of the
      glutamine synthetase protein, and the effect was partially blocked by the
      proteasome inhibitor MG132. The addition of the glutamine structural analog and
      glutaminase inhibitor, 6-diazo-5-oxo-L-norleucine, in the presence or absence of
      glutamine, also resulted in low glutamine synthetase protein levels. Otherwise,
      the effect was specific for glutamine, and the only compounds able to mimic the
      effect of glutamine were amino acids, glutamate, alanine, and ornithine, which
      can be converted to glutamine. Other amino acids, analogs, and products of
      glutamine metabolism were without effect. Methionine sulfoximine, an inhibitor of
      glutamine synthetase, stabilized the protein and prevented the glutamine effect.
      Thus, in mouse C2C12 skeletal muscle cells, glutamine synthetase protein
      expression is regulated by glutamine through changes in the rate of degradation
      of the protein. The effect is specific to glutamine, which acts directly without
      requiring prior metabolism.

PMID- 17513392
TI  - Conjugated linoleic acid affects lipid composition, metabolism, and gene
      expression in gilthead sea bream (Sparus aurata L).
AB  - To maximize growth, farmed fish are fed high-fat diets, which can lead to high
      tissue lipid concentrations that have an impact on quality. The intake of
      conjugated linoleic acid (CLA) reduces body fat in mammals and this study was
      undertaken to determine the effects of dietary CLA on growth, composition, and
      postprandial metabolic variables in sea bream. Fish were fed 3 diets containing
      48 g/100 g protein and 24 g/100 g fat, including fish oil supplemented with 0
      (control), 2, or 4% CLA for 12 wk. Feed intake, specific growth rate, total body
      fat, and circulating somatolactin concentration were lower in fish fed CLA than
      in controls. Feed efficiency was greater in fish fed 2% CLA than in controls.
      Liver triglyceride concentrations were higher in fish fed 4% CLA and muscle
      triglyceride concentrations were lower in fish fed both CLA diets than in
      controls. Hepatic fatty acyl desaturase and elongase mRNA levels in fish fed CLA
      were lower than in controls. Metabolic differences between controls and CLA-fed
      fish were observed at 6 h but not at 24 h after the last meal, including lower
      postprandial circulating triglyceride concentrations, higher hepatic acyl-CoA
      oxidase, and lower L-3-hydroxyacyl-CoA dehydrogenase activities in CLA-fed fish
      than in controls. Dietary CLA did not affect enzymes involved in lipogenesis
      including hepatic fatty acid synthase and malic enzyme, but it decreased glucose
      6-phosphate dehydrogenase activity at 24 h, but not at 6 h after feeding. The
      data suggest that CLA intake in sea bream has little effect on hepatic
      lipogenesis, channels dietary lipid from adipose tissue to the liver, and
      switches hepatic mitochondrial to peroxisomal beta-oxidation.

PMID- 17513393
TI  - Copper deficiency decreases plasma homocysteine in rats.
AB  - The purpose of this study was to determine the effects of copper deficiency on
      key aspects of homocysteine metabolism that involve methionine recycling and
      transsulfuration. Male weanling Sprague-Dawley rats were fed AIN-93G-based diets
      containing <1 or approximately 6 mg Cu/kg. After 6 wk (Expt. 1) and 4 wk (Expt.
      2) we found that plasma homocysteine was significantly decreased, and plasma
      glutathione significantly increased, in rats fed the low-Cu diet. Real-time RT
      PCR was used to determine the expression of the subunits of glutamate-cysteine
      ligase (Gcl) in liver that catalyzes the rate-limiting step in glutathione
      biosynthesis. The expression of Gclc, the catalytic subunit of Gcl, was
      upregulated by Cu deficiency; Gclm, the modifier subunit, was not affected.
      Hepatic betaine-homocysteine methyltransferase (Bhmt), which catalyzes one of the
      two ways that homocysteine can be remethylated to methionine, was downregulated
      by Cu deficiency. Because Cu deficiency results in upregulation of Gclc and an
      increase in the biosynthesis of glutathione, it is plausible that the net flux of
      homocysteine through the transsulfuration pathway is increased. Furthermore, if
      Bhmt is downregulated, less homocysteine is available for remethylation
      (methionine recycling) and more is then available to irreversibly enter the
      transsulfuration pathway where it is lost. The net effect of increased Gclc and
      decreased Bhmt would be a decrease in homocysteine as a result of Cu deficiency.

PMID- 17513394
TI  - Avenanthramides are bioavailable and have antioxidant activity in humans after
      acute consumption of an enriched mixture from oats.
AB  - The consumption of polyphenols is associated with a decreased risk of
      cardiovascular disease. Avenanthramides (AV), alkaloids occurring only in oats,
      may have anti-atherosclerotic activity, but there is no information concerning
      their bioavailability and bioactivity in humans. We characterized the
      pharmacokinetics and antioxidant action of avenanthramide A, B, and C in healthy
      older adults in a randomized, placebo-controlled, 3-way crossover trial with 1-wk
      washout periods. Six free-living subjects (3 mol/L, 3 F; 60.8 +/- 3.6 y) consumed
      360 mL skim milk alone (placebo) or containing 0.5 or 1 g avenanthramide-enriched
      mixture (AEM) extracted from oats. Plasma samples were collected over a 10-h
      period. Concentrations of AV-A, AV-B, and AV-C in the AEM were 154, 109, and 111
      micromol/g, respectively. Maximum plasma concentrations of AV (free + conjugated)
      after consumption of 0.5 and 1 g AEM were 112.9 and 374.6 nmol/L for AV-A, 13.2
      and 96.0 nmol/L for AV-B, and 41.4 and 89.0 nmol/L for AV-C, respectively. Times
      to reach the C(max) for both doses were 2.30, 1.75, and 2.15 h for AV-A, AV-B,
      and AV-C and half times for elimination were 1.75, 3.75, and 3.00 h,
      respectively. The elimination kinetics of plasma AV appeared to follow first
      order kinetics. The bioavailability of AV-A was 4-fold larger than that of AV-B
      at the 0.5 g AEM dose. After consumption of 1 g AEM, plasma reduced glutathione
      was elevated by 21% at 15 min (P < or = 0.005) and by 14% at 10 h (P < or =
      0.05). Thus, oat AV are bioavailable and increase antioxidant capacity in healthy
      older adults.

PMID- 17513395
TI  - Meal amino acids with varied levels of arginine do not affect postprandial
      vascular endothelial function in healthy young men.
AB  - Postprandial endothelial dysfunction is a key event mediating the effects of diet
      on early atherogenesis. The potential effects of protein intake have been
      overlooked in the past, although amino acids are precursors for homocysteine and
      nitric oxide (NO). Our objective was to study the effect of amino acids on
      postprandial vascular function, in relation to the utilization of meal arginine
      for NO production. In a crossover design, 9 men ingested 50 g of a complete amino
      acid mixture, trace-labeled with (13)C-glycine and (15)N(2)-arginine, without
      (meal A) or with (meal B) 3 g extra arginine. The postprandial utilization of
      meal arginine for NO production was determined from urinary (15)NO(3). We
      monitored endothelial function of the brachial artery, the stiffness of the
      common carotid artery, aortic pulse wave velocity and soluble markers related to
      endothelial function for 8 h. Meal A did not significantly increase plasma
      homocysteine and did not alter endothelial function markers. The amount of NO
      synthesized from meal arginine doubled after meal B (107.1 +/- 16.5% increase vs.
      meal A, P < 0.01) but was very low (271 +/- 84 ppm vs. 332 +/- 73 ppm, P < 0.05,
      respectively). After meal B, flow-mediated and nitroglycerine-induced dilation
      decreased but common carotid artery compliance, pulse wave velocity, plasma
      soluble intercellular adhesion molecule-1, and von Willebrand factor, and urinary
      cGMP did not differ when compared with meal A. Together, the data indicate that,
      in healthy men, meal amino acids do not adversely affect endothelial function,
      and meal arginine only slightly enters the NO pathway. Unexpectedly, arginine in
      physiological amounts may acutely lessen smooth muscle cell reactivity to a high
      dynamic NO release.

PMID- 17513396
TI  - Dietary soy protein containing isoflavonoids does not adversely affect the
      reproductive tract of male cynomolgus macaques (Macaca fascicularis).
AB  - Short-term dietary studies of soy-protein-derived isoflavonoids, using rodent and
      nonhuman primate models, have documented variable effects on the reproductive
      tract. Long-term effects of dietary soy and/or isoflavonoids on the reproductive
      tract of nonhuman primates have not been determined. The objective of this study
      was to assess the effects of long-term consumption of dietary soy isoflavonoids
      on histomorphology of the mammary glands and prostate gland, testis, and sperm
      counts in adult male cynomolgus macaques. Ninety-one adult male cynomolgus
      macaques (Macaca fascicularis) were fed diets for 3 y differing only in protein
      source: 1) a soy-free, casein-lactalbumin-based diet or 2) a low-soy isoflavonoid
      diet ( approximately 6 mg . kg(-1) . d(-1)) or 3) a high-soy isoflavonoid diet (
      approximately 12 mg . kg(-1) . d(-1)). Serum isoflavonoids were measured by
      liquid chromatographic-photodiode array electrospray MS. Mammary gland, prostate
      gland, and testes were obtained at postmortem and evaluated histopathologically
      and histomorphometrically. Epididymal and testicular sperm counts were performed.
      Serum isoflavonoid concentrations at 4 h postfeeding differed among all groups (P
      < 0.001) and were (means +/- SEM) 67 +/- 23 (soy-free diet), 799 +/- 44 (low-soy
      isoflavonoid diet), and 1458 +/- 80 nmol . L(-1) (high-soy isoflavonoid diet).
      Diet did not alter serum estradiol and testosterone concentrations or epididymal
      and testicular sperm counts. Organ weights and histologic indices did not differ
      among treatment groups. Mammary gland histopathologic and histomorphometric
      analysis revealed no abnormalities and no indication of gynecomastia. We found no
      evidence of an adverse effect of soy isoflavonoids at physiologically relevant
      doses within the reproductive organs of adult male macaques.

PMID- 17513397
TI  - Beta-carotene from red carrot maintains vitamin A status, but lycopene
      bioavailability is lower relative to tomato paste in Mongolian gerbils.
AB  - Red carrots contain lycopene in addition to alpha- and beta-carotene. The utility
      of red carrot as a functional food depends in part on the bioavailability of its
      constituent carotenoids. Lycopene bioavailability was compared in Mongolian
      gerbils (Meriones unguiculatus) fed freeze-dried red carrot and tomato paste
      (Study 1, n = 47) and whole food extracts dissolved in cottonseed oil (Study 2, n
      = 39). Diets and supplements were equalized for lycopene and intakes did not
      differ. Both studies utilized negative (oil) and positive [purified lycopene
      (Lyc)] controls. In Study 1, vitamin A liver stores (0.68 +/- 0.13
      micromol/liver) of the red carrot group did not differ from baseline (0.63 +/-
      0.13 micromol/liver) and were greater than those of the tomato paste (0.43 +/-
      0.12 micromol/liver), Lyc (0.51 +/- 0.14 micromol/liver), and control (0.38 +/-
      0.17 micromol/liver) groups (P < 0.003). A similar pattern was observed in Study
      2. In both studies, hepatic lycopene was higher in the tomato paste (82.7 +/-
      26.7 and 80.7 +/- 20.2 nmol/liver) groups compared with red carrot groups (59.3
      +/- 21.9 and 39.5 +/- 14.1 nmol/liver, P < 0.0001). Hepatic lycopene from tomato
      paste was higher than Lyc in Study 1, but tomato paste extract and Lyc did not
      differ in Study 2, when both were dissolved in oil. Red carrot maintains vitamin
      A status, but constituent beta-carotene may interfere with lycopene
      bioavailability. These results confirm prior studies in humans on the relative
      bioavailability of lycopene from red carrots and tomato paste and expand them by
      suggesting the mechanism and determining vitamin A value.

PMID- 17513398
TI  - Whole-grain foods do not affect insulin sensitivity or markers of lipid
      peroxidation and inflammation in healthy, moderately overweight subjects.
AB  - High intakes of whole grain foods are inversely related to the incidence of
      coronary heart diseases and type 2 diabetes, but the mechanisms remain unclear.
      Our study aimed to evaluate the effects of a diet rich in whole grains compared
      with a diet containing the same amount of refined grains on insulin sensitivity
      and markers of lipid peroxidation and inflammation. In a randomized crossover
      study, 22 women and 8 men (BMI 28 +/- 2) were given either whole-grain or refined
      grain products (3 bread slices, 2 crisp bread slices, 1 portion muesli, and 1
      portion pasta) to include in their habitual daily diet for two 6-wk periods.
      Peripheral insulin sensitivity was determined by euglycemic hyperinsulinemic
      clamp tests. 8-Iso-prostaglandin F(2alpha) (8-iso PGF(2alpha)), an F(2)
      isoprostane, was measured in the urine as a marker of lipid peroxidation, and
      highly sensitive C-reactive protein and IL-6 were analyzed in plasma as markers
      of inflammation. Peripheral insulin sensitivity [mg glucose . kg body wt(-1) .
      min(-1) per unit plasma insulin (mU/L) x 100] did not improve when subjects
      consumed whole-grain products (6.8 +/- 3.0 at baseline and 6.5 +/- 2.7 after 6
      wk) or refined products (6.4 +/- 2.9 and 6.9 +/- 3.2, respectively) and there
      were no differences between the 2 periods. Whole-grain consumption also did not
      affect 8-iso-PGF(2alpha) in urine, IL-6 and C-reactive protein in plasma, blood
      pressure, or serum lipid concentrations. In conclusion, substitution of whole
      grains (mainly based on milled wheat) for refined-grain products in the habitual
      daily diet of healthy moderately overweight adults for 6-wk did not affect
      insulin sensitivity or markers of lipid peroxidation and inflammation.

PMID- 17513399
TI  - Dietary encapsulated glycine influences Clostridium perfringens and Lactobacilli
      growth in the gastrointestinal tract of broiler chickens.
AB  - Three experiments were conducted to determine whether there is a causative
      relation between dietary glycine concentration and intestinal Clostridium
      perfringens growth in broiler chickens. Expt. 1 showed that glycine
      concentrations were higher (P < 0.05) in jejunum and ileum of birds fed fat
      encapsulated glycine compared with crystalline glycine. In Expt. 2, 2 cages of 6
      birds were assigned to 1 of 6 experimental diets formulated to contain 7.6 and
      10.6, 17.8 and 40.6, 27.8 and 30.6, 37.8 and 20.6, 47.7 and 10.6, and 7.8 and
      50.6 g/kg total glycine and proline, respectively, provided primarily by
      supplementation with encapsulated glycine or proline as required. In Expt. 3, 12
      groups of 6 birds were fed 4 different diets supplemented with encapsulated
      glycine to achieve 7.6, 21.0, 34.3, or 47.7 g/kg total glycine. The birds were
      orally challenged with C. perfringens type A on d 1 and d 14-21 and killed on d
      28. In Expt. 2, C. perfringens populations were higher (P < 0.05) in ileum and
      cecum of birds, which received either 37.8 or 47.7 g/kg total glycine compared
      with those fed 7.6 g/kg glycine. In Expt. 3, C. perfringens numbers were higher
      (P < 0.05) in ileum of birds fed either 34.3 or 47.7 g/kg dietary glycine than
      those given either 7.6 or 21.0 g/kg glycine. Conversely, lactobacilli counts in
      ileum and cecum were significantly lower in birds fed the higher levels of
      glycine in both experiments. High C. perfringens colonization and high intestinal
      lesion scores were associated with reduced performance (P < 0.05). We conclude
      that glycine is an important determinant of C. perfringens growth in the
      intestinal tract of broiler chickens.

PMID- 17513400
TI  - Whole-food sources of vitamin A more effectively inhibit female rat sexual
      maturation, mammary gland development, and mammary carcinogenesis than retinyl
      palmitate.
AB  - Previous work using an adolescent rat model for breast cancer showed increased
      tumor occurrence in rats fed a chemopreventive dose of vitamin A. Preclinical
      models for nutrient-cancer interactions utilizing defined diets do not replicate
      the complexity of the human diet and may be inadequate to investigate food
      patterns associated with reduced cancer risk in humans. To evaluate this concept,
      the effects of vitamin A on sexual maturation, mammary gland development, and
      sensitivity to carcinogenesis were determined in the context of a human food
      based diet (whole food diet). At 20 d of age (p20), female rats received either a
      whole-food diet with adequate levels of vitamin A, a diet with a 5.5-fold
      increase in vitamin A from fruits and vegetables (S diet), or a diet with a 6.2
      fold increase in vitamin A provided as retinyl palmitate (RP diet). To determine
      the effect of dietary intervention on pubertal mammary gland development, the
      dietary intervention period was restricted to postnatal d 21-63. Rats were
      injected with 50 mg 1-methyl-1-nitrosourea/kg body weight at d 66. Compared with
      adolescent rats that consumed the Ad diet, consumption of S and RP diets reduced
      mammary cancer multiplicity (relative risk approximately 0.7, P < or = 0.002),
      which was associated with a reduction in alveolar gland development. The S diet
      suppressed the onset of sexual maturation (P < 0.001) and inhibited markers of
      mammary alveologenesis more than the RP diet. These data demonstrate that the
      amount and source of vitamin A consumed by adolescent female rats can influence
      the onset of puberty, mammary gland alveolar development, and breast cancer risk
      and highlight the relevance of utilizing whole-food diets to evaluate the role of
      dietary factors in cancer prevention.

PMID- 17513401
TI  - Conjugated linoleic acid alters matrix metalloproteinases of metastatic mouse
      mammary tumor cells.
AB  - Conjugated linoleic acid (CLA) is a group of linoleic acid derivatives that has
      been implicated in animal studies to reduce a number of components of mammary
      tumorigenesis. Previously, we showed that CLA could alter the latency and
      metastasis of the highly metastatic transplantable line 4526 mouse mammary tumor.
      Several possible mechanisms have been proposed for the actions of CLA, but here
      we assessed how CLA may act to alter the expression and activity of matrix
      modifying proteins within tumors from line 4526. In vitro, highly metastatic
      mouse mammary tumor cells had significantly decreased invasiveness after
      treatment with CLA, an indication that matrix-modifying proteins may have been
      altered. Using these same highly metastatic cells, primary tumors were grown in
      mice of separate groups fed 0, 0.1, 0.5, and 1% CLA (wt:wt) and evaluated for
      their levels and activities of matrix-modifying enzymes, enzyme inhibitors, and
      enzyme activators. The addition of CLA to the diet increased steady-state levels
      of messenger RNA (mRNA) of the matrix metalloproteinases (MMP) -2 and -9 in
      primary tumors removed from mice. However, western analysis revealed that
      although relative levels of the proform of MMP-9 were consistent with the mRNA
      observations, MMP-2 proform levels were actually decreased by dietary CLA. The
      activity of MMP-2 was barely detectable, but gelatin zymography and an in vitro
      activity assay showed that MMP-9 activity was significantly decreased by CLA. The
      steady-state mRNA and protein levels of tissue inhibitors of metalloproteinase-1
      (TIMP-1) and TIMP-2, natural inhibitors of MMP, were increased at higher dietary
      CLA levels relative to low or no CLA. Suppression of MMP activity, therefore, may
      be 1 pathway through which CLA reduces tumor invasion and spread.

PMID- 17513402
TI  - Gamma-linolenate reduces weight regain in formerly obese humans.
AB  - The purpose of this study was to determine whether gamma-linolenate (GLA)
      supplementation would suppress weight regain following major weight loss. Fifty
      formerly obese humans were randomized into a double-blind study and given either
      890 mg/d of GLA (5 g/d borage oil) or 5 g/d olive oil (controls) for 1 y. Body
      weight and composition and adipose fatty acids of fasting subjects were assessed
      at 0, 3, 12, and 33 mo. After 12 subjects in each group had completed 1 y of
      supplementation, weight regain differed between the GLA (2.17 +/- 1.78 kg) and
      control (8.78 +/- 2.78 kg) groups (P < 0.03). The initial study was terminated,
      and all remaining subjects were assessed over a 6-wk period. Unblinding revealed
      weight regains of 1.8 +/- 1.6 kg in the GLA group and 7.6 +/- 2.1 kg in controls
      for the 13 and 17 subjects, respectively, who completed a minimum of 50 wk in the
      study. Weight regain did not differ in the remaining 10 GLA and 5 control
      subjects who completed <50 wk in the study. In a follow-up study, a subgroup from
      both the original GLA (GLA-GLA, n = 9) and the original control (Control-GLA, n =
      14) populations either continued or crossed over to GLA supplementation for an
      additional 21 mo. Interim weight regains between 15 and 33 mo were 6.48 +/- 1.79
      kg and 6.04 +/- 2.52 kg for the GLA-GLA and Control-GLA groups, respectively.
      Adipose triglyceride GLA levels increased 152% (P < 0.0001) in the GLA group at
      12 mo, but did not increase further after 33 mo of GLA administration. In
      conclusion, GLA reduced weight regain in humans following major weight loss,
      suggesting a role for essential fatty acids in fuel partitioning in humans prone
      to obesity.

PMID- 17513403
TI  - Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in
      normo- and hypercholesterolemic humans after intake of different levels of cocoa
      powder.
AB  - Cocoa powder is rich in polyphenols, such as catechins and procyanidins, and has
      been shown in a variety of subject models to inhibit oxidized LDL and
      atherogenesis. Our study evaluated plasma LDL cholesterol and oxidized LDL
      concentrations following the intake of different levels of cocoa powder (13,
      19.5, and 26 g/d) in normocholesterolemic and mildly hypercholesterolemic humans.
      In this comparative, double-blind study, we examined 160 subjects who ingested
      either cocoa powder containing low-polyphenolic compounds (placebo-cocoa group)
      or 3 levels of cocoa powder containing high-polyphenolic compounds (13, 19.5, and
      26 g/d for low-, middle-, and high-cocoa groups, respectively) for 4 wk. The test
      powders were consumed as a beverage after the addition of hot water, twice each
      day. Blood samples were collected at baseline and 4 wk after intake of the test
      beverages for the measurement of plasma lipids. Plasma oxidized LDL
      concentrations decreased in the low-, middle-, and high-cocoa groups compared
      with baseline. A stratified analysis was performed on 131 subjects who had a LDL
      cholesterol concentrations of > or =3.23 mmol/L at baseline. In these subjects,
      plasma LDL cholesterol, oxidized LDL, and apo B concentrations decreased, and the
      plasma HDL cholesterol concentration increased, relative to baseline in the low-,
      middle-, and high-cocoa groups. The results suggest that polyphenolic substances
      derived from cocoa powder may contribute to a reduction in LDL cholesterol, an
      elevation in HDL cholesterol, and the suppression of oxidized LDL.

PMID- 17513404
TI  - A deficiency or excess of dietary threonine reduces protein synthesis in jejunum
      and skeletal muscle of young pigs.
AB  - Dietary threonine imbalance is known to reduce the growth of the small intestine,
      liver, and skeletal muscle in young animals, but the underlying mechanism is
      largely unknown. Using the pig model, this study was conducted to test the
      hypothesis that either a deficiency or an excess of dietary threonine impairs
      protein synthesis in these tissues. Young pigs (25 d of age) were fed diets
      containing 0.37, 0.74 (current NRC requirement) or 1.11% true ileal digestible
      threonine (TIDT) (n = 6/diet). Pigs receiving the 0.74 and 1.11% TIDT diets were
      pair-fed with the same amount of feed as pigs receiving the 0.37% TIDT diet.
      After a 14-d dietary treatment, the fractional synthesis rate (FSR) of protein in
      tissues was measured using a flooding dose of l-phenylalanine plus L-[ring
      (2)H(5)]phenylalanine. The results indicated that the FSR of protein in liver was
      reduced (P < 0.05) in pigs fed the 0.37% TIDT diet compared with pigs fed the
      0.74 or 1.11% TIDT diet, and did not differ between pigs fed the 0.74 and 1.11%
      TIDT diets. The FSR of protein in longissimus muscle, jejunal mucosa, and mucins
      was reduced (P < 0.05) in pigs fed the 0.37 or 1.11% TIDT diet compared with pigs
      fed the 0.74% TIDT diet. The absolute synthesis rate of protein in the jejunal
      mucosa and muscle was also reduced (P < 0.01) in pigs fed the 0.37 and 1.11% TIDT
      diets compared with the controls. The absolute synthesis rate of hepatic protein
      was lower (P < 0.01) in pigs fed the 0.37% TIDT diets when compared with pigs fed
      the 0.74% TIDT diet. Protein synthesis in skeletal muscle as well as jejunal
      mucosa and mucins was reduced to a greater extent than that in liver in response
      to an imbalance of dietary threonine. Collectively, these results indicate that
      either an excess or a deficiency of dietary threonine decreases protein synthesis
      in rapidly growing tissues of young pigs. The findings provide a mechanism for
      the low growth performance of animals fed a threonine-imbalanced diet.

PMID- 17513405
TI  - Consumption of sweetened beverages and intakes of fructose and glucose predict
      type 2 diabetes occurrence.
AB  - The role of intakes of different sugars in the development of type 2 diabetes was
      studied in a cohort of 4,304 men and women aged 40-60 y and initially free of
      diabetes at baseline in 1967-1972. Food consumption data were collected using a
      dietary history interview covering the habitual diet during the previous year.
      The intakes of different sugars were calculated and divided in quartiles. During
      a 12-y follow-up, 177 incidents of type 2 diabetes cases were identified from a
      nationwide register. Combined intake of fructose and glucose was associated with
      the risk of type 2 diabetes but no significant association was observed for
      intakes of sucrose, lactose, or maltose. The relative risk between the highest
      and lowest quartiles of combined fructose and glucose intake was 1.87 (95% [CI] =
      1.19, 2.93; P = 0.003). The corresponding relative risks between the extreme
      quartiles of consumption of food items contributing to sugar intakes were 1.69
      (95% [CI] = 1.17, 2.43; P < 0.001) for sweetened berry juice and 1.67 (95% [CI] =
      0.98, 2.87; P = 0.01) for soft drinks. Our findings support the view that higher
      intake of fructose and glucose and sweetened beverages may increase type 2
      diabetes risk.

PMID- 17513406
TI  - Benefit of vitamin A supplementation on ascaris reinfection is less evident in
      stunted children.
AB  - Despite the common coexistence of vitamin A deficiency and Ascaris infection in
      preschool children in developing countries, and despite the widespread use of
      vitamin A supplements, remarkably little is understood about the impact of
      vitamin A supplementation on this gastrointestinal nematode. The Ministry of
      Health of Panama recently initiated a vitamin A supplementation program in rural
      indigenous populations. We took advantage of this initiative to assess the
      benefit of 200,000 IU (60 mg retinol) vitamin A on reinfection with Ascaris
      following deworming. Baseline stool exams, anthropometry, and socio-economic data
      were collected for 328 preschool children from 12-60 mo of age (106 supplemented
      within previous 3 mo and 222 unsupplemented within previous 6 mo). All children
      were dewormed with albendazole, and reinfection levels were monitored 3 and 5 mo
      later. Baseline prevalence of Ascaris was 79.5%. Stepwise regression showed that
      Ascaris intensity was lower in Vit A-supplemented children at baseline and 3 mo
      after deworming, but not after 5 mo. As 61% of the children were stunted, the
      impact of supplementation on Ascaris reinfection was examined separately for
      stunted and children of normal height. Prevalence and intensity of Ascaris at
      baseline and 3 mo after deworming were lower in children of normal height, but in
      stunted children the benefit was restricted to those who were dewormed within 6
      wk of supplementation. Our study provides evidence that combined vitamin A
      supplementation and deworming reduces Ascaris reinfection in children living in
      areas of chronic parasitosis, but that the duration of the benefit is less in
      stunted children.

PMID- 17513407
TI  - Gender and marital status clarify associations between food insecurity and body
      weight.
AB  - Prior research shows that food insecurity is associated with being overweight in
      women, with few and ambiguous results in men. Little is known about the
      characteristics and roles of individuals who are most likely to be both food
      insecure and overweight or obese. This study analyzed associations between food
      insecurity and body weight, and whether gender and marital status are involved in
      that relationship. Using multiple regression models, we examined food insecurity,
      marriage, and body weight among 4338 men and 4172 women aged > or = 20 y in the
      1999-2002 NHANES. Married men were more likely to be overweight than men in all
      other marital-status categories except for those living with partners. Divorced
      men were more likely than never-married men to live in a household with very low
      food security. Compared with fully food-secure men, marginally food-secure men
      were heavier, whereas men with low food security were lighter. Compared with
      fully food-secure women, marginally food-secure women also showed a tendency to
      be overweight (P = 0.05), whereas women with low food security were more likely
      to be obese. When considering the interaction between food insecurity and marital
      status, food insecurity was related to a greater likelihood of obesity among
      married women, those living with partners, and widows, when compared with never
      married women. Sensitivity analyses suggest this effect was concentrated among
      marginally food-secure women. These findings indicate that food insecurity
      relates differently to body weight for men and women, and that partnering plays a
      strong part in this relationship for women.

PMID- 17513408
TI  - Decreased selenoprotein expression alters the immune response during influenza
      virus infection in mice.
AB  - Previous work from our laboratory demonstrated that host selenium (Se) deficiency
      results in greater lung pathology and altered immune function in mice infected
      with influenza virus. Because selenoproteins play a key role in determining the
      oxidant status of the host, we utilized a transgenic mouse line carrying a mutant
      selenocysteine (Sec) tRNA ([Ser]Sec) transgene (t-trspi(6)A(-)). The levels of
      selenoproteins are decreased in these mice in a protein- and tissue-specific
      manner. Male t-trspi(6)A(-) and wild-type (WT) mice were infected with influenza
      and killed at various time points postinfection (p.i.). Lung mRNA levels for
      innate and pro-inflammatory cytokines increased with infection but did not differ
      between groups. However, at d 2 p.i., chemokine levels were greater in the t
      trspi(6)A(-) mice compared with WT mice. Additionally, IFN-gamma was higher at d
      7 p.i. in the t-trspi(6)A(-) mice and viral clearance slower. Despite these
      immune system changes, lung pathology was similar in t-trspi(6)A(-) and WT mice.
      (75)Se labeling experiments demonstrated that glutathione peroxidase (GPX)-1 and
      thioredoxin reductase, although greatly diminished in the lungs of t-trspi(6)A(-)
      mice, were not altered as a result of infection. GPX-1 activity in the lungs of
      the t-trspi(6)A(-) mice was approximately 82% of the WT mice. In addition, the
      GPX-1 activity in the lungs of Se-deficient mice was 125% less than in the t
      trspi(6)A(-) mice. These results suggest that although selenoproteins are
      important for immune function, there is a threshold of GPX-1 activity that can
      prevent an increase in lung pathology during influenza infection.

PMID- 17513409
TI  - Dietary supplementation with white button mushroom enhances natural killer cell
      activity in C57BL/6 mice.
AB  - Mushrooms are reported to possess antitumor, antiviral, and antibacterial
      properties. These effects of mushrooms are suggested to be due to their ability
      to modulate immune cell functions. However, a majority of these studies evaluated
      the effect of administering extracts of exotic mushrooms through parental routes,
      whereas little is known about the immunological effect of a dietary intake of
      white button mushrooms, which represent 90% of mushrooms consumed in the U.S. In
      this study, we fed C57BL/6 mice a diet containing 0, 2, or 10% (wt/wt) white
      button mushroom powder for 10 wk and examined indices of innate and cell-mediated
      immunity. Mushroom supplementation enhanced natural killer (NK) cell activity,
      and IFNgamma and tumor necrosis factor-alpha (TNFalpha) production, but only
      tended to increase IL-2 (P = 0.09) and did not affect IL-10 production by
      splenocytes. There were significant correlations between NK activity and
      production of IFNgamma (r = 0.615, P < 0.001) and TNFalpha (r = 0.423, P = 0.032)
      in splenocytes. Mushroom supplementation did not affect macrophage production of
      IL-6, TNFalpha, prostaglandin E(2), nitric oxide, and H(2)O(2), nor did it alter
      the percentage of total T cells, helper T cells (CD4(+)), cytotoxic or
      suppressive T cells (CD8(+)), regulatory T cells (CD4(+)/CD25(+)), total B cells,
      macrophages, and NK cells in spleens. These results suggest that increased intake
      of white button mushrooms may promote innate immunity against tumors and viruses
      through the enhancement of a key component, NK activity. This effect might be
      mediated through increased IFNgamma and TNFalpha production.

PMID- 17513410
TI  - Inadequate dietary protein increases hunger and desire to eat in younger and
      older men.
AB  - Many older people experience changes in appetite and consume marginal or
      inadequate dietary protein. This study was designed to examine the appetitive
      responses to habitual protein intakes that span the range of adequacy in younger
      and older men. Twenty-two men (12 younger, aged 21-43 y and 10 older, aged 63-79
      y) completed, in random order, three 18-d trials that involved consumption of
      individualized, isoenergetic menus providing 1.00, 0.75, and 0.50 g protein . kg
      BW(-1). d(-1), which were 125% (trial P125), 94% (trial P94), and 63% (trial P63)
      of the Recommended Dietary Allowance for protein. Near the end of each trial, the
      subjects recorded appetitive sensations hourly throughout one day using a visual
      analogue scale. Independent of age, ratings of hunger were lower for P125 (1.3 +/
      0.5 cm) than P94 (1.8 +/- 0.8 cm) and P63 (1.8 +/- 0.6 cm) (P = 0.037), and
      desire to eat was lower during the P125 trial (1.4 +/- 0.5 cm), compared with the
      P63 trial (2.1 +/- 0.7 cm) (P = 0.003), and P94 (1.8 +/- 0.7 cm) was not
      different when compared with P63 and P125. Protein intake did not influence
      fullness. These results show that younger and older men who consume inadequate
      protein experience appetite changes that may promote increased food intake.

PMID- 17513411
TI  - Solid and liquid obesogenic diets induce obesity and counter-regulatory changes
      in hypothalamic gene expression in juvenile Sprague-Dawley rats.
AB  - Contemporary foods and beverages that constitute the diets of adults and children
      almost certainly contribute to the obesity problem. To develop a model of
      childhood obesity, we examined the effects of feeding juvenile rats 2 solid
      diets, either alone or in combination [nonpurified control diet (C), high-energy
      (HE), or C+HE] with or without the liquid supplement Ensure (EN). Rats were fed C
      until 4 wk of age and then were assigned to 1 of 6 weight-matched groups that
      were fed C, HE, C+HE, C+EN, HE+EN, or C+HE+EN for 5 wk. EN accelerated weight
      gain and increased energy intake and adiposity irrespective of the solid diet
      consumed. Serum leptin concentrations were increased after the consumption of all
      diets when compared with C rats, but there was dissociation between leptin levels
      and adiposity. The type of solid diet had no effect on the expression of a panel
      of hypothalamic genes except for glutamate-decarboxylase-67. EN decreased mRNA
      for agouti-related peptide and neuropeptide Y in the arcuate nucleus and DYN in
      the paraventricular nucleus. Dynorphin and CART mRNA were decreased in the
      supraoptic retrochiasmatic nucleus. The reduction in orexigenic signaling in the
      hypothalamus suggests that overconsumption of EN is sensed by the hypothalamus
      but that any initiated physiological responses fail to compensate effectively and
      may be negated or overwhelmed by other systems. Providing diets in solid and
      liquid form, with choice, mimics more closely the human environment.
      Understanding the interactions between these diets and peripheral and central
      energy balance systems could be crucial in unraveling the events underlying human
      obesity and its early development.

PMID- 17513412
TI  - Standardizing terminology for estimating the diet-dependent net acid load to the
      metabolic system.

PMID- 17513413
TI  - Total antioxidant capacity: appraisal of a concept.
AB  - In this contribution, I discuss the applicability of total antioxidant capacity
      (TAC) data obtained from plasma to human health issues and the use of TAC data
      for dietary items in epidemiological applications. Against the background of
      knowledge that major antioxidant defense is enzymatic, the use of the term
      "total" is not appropriate. Because dietary phytochemicals undergo uptake and
      metabolism, extrapolation to health effects requires direct molecular
      information, not a global parameter that uses an arbitrarily selected prooxidant
      source. Suitable alternatives are given in measuring functional biomarkers
      (surrogate endpoints). Although using TAC may be helpful in comparing different
      food items, the extrapolation to their contribution of antioxidant defense in
      vivo and, further, to health issues, should be discouraged, with the possible
      exception of the gastrointestinal tract. This is of particular importance because
      dietary phytochemicals and other small molecules have nonantioxidant activities.
      Direct assay of urate, ascorbate, and tocopherol, the major small-molecule
      contributors to TAC, is recommended.

PMID- 17513414
TI  - Value or usefulness of the food frequency questionnaire for the assessment of
      dietary total antioxidant capacity.

PMID- 17513416
TI  - Cation-pi interactions involving aromatic amino acids.
AB  - The cation-pi interaction is a general, strong, noncovalent binding force that is
      used throughout nature. The side chains of the aromatic amino acids
      [phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp)] provide a surface of
      negative electrostatic potential than can bind to a wide range of cations through
      a predominantly electrostatic interaction. In this brief overview, the
      fundamental nature of the cation-pi interaction will be described, relying on
      fundamental, gas phase studies of the effect. Then, several examples of cation-pi
      interactions involving aromatic amino acids will be described. These include
      contributions to protein secondary structure, in which Phe/Tyr/Trp...lysine
      (Lys)/arginine interactions are common. We will also describe several examples of
      protein-ligand interactions that make use of cation-pi interactions. We will
      place special emphasis on the binding of quaternary ammonium ions, such as
      trimethylated Lys and the neurotransmitter acetylcholine.

PMID- 17513417
TI  - Molecular mechanisms of conduction and selectivity in aquaporin water channels.
AB  - Aquaporins (AQP) are a family of membrane channels primarily responsible for
      conducting water across cellular membranes. The availability of a large body of
      high resolution structural data along with numerous atomic-scale simulation
      studies have resulted in an unprecedented level of understanding of the mechanism
      of function and selectivity in AQP. In this article, after summarizing major
      highlights of structure-functional studies of AQP, we will report on some of our
      recent large-scale molecular dynamics simulations investigating the mechanisms of
      permeation of various substances through pure lipid bilayers and through multiple
      pathways provided by tetrameric structures of different AQP. Comparison of the
      results obtained for structurally highly homologous, but functionally distinct,
      AQP allowed us to identify novel mechanisms of gating and selectivity of these
      channels and to design mutants with experimentally verified, altered properties.
      When applicable, special attention will be given to specific aromatic amino acids
      and their involvement in various functional aspects of AQP.

PMID- 17513418
TI  - c-Abl tyrosine kinase and inhibition by the cancer drug imatinib (Gleevec/STI
      571).
AB  - The search for specific protein kinase inhibitors is an intense area of research
      because of the potential for drug development. The small-molecule inhibitor
      imatinib (Gleevec/STI-571) can specifically inactivate the tyrosine kinase c-Abl,
      whose normal mechanism of autoinhibition is disrupted in chronic myelogenous
      leukemia. Crystallographic analysis of c-Abl reveals that imatinib recognizes a
      distinct inactive conformation of the Abl kinase domain that relies on the
      mechanism of autoinhibition achieved in the context of a larger fragment of the
      protein. This mechanism is distinct from that seen in the related Src family
      kinases, where autoinhibition is achieved through the internal engagement of a C
      terminal phosphotyrosine residue by the Src homology 2 domain (SH2) domain.
      Notably, this phosphotyrosine residue is lacking in c-Abl, where instead
      autoinhibition is mediated by an interaction between the kinase domain and the N
      terminal myristoyl modification. Within the framework of these 2 distinct modes
      of autoinhibition, the SH3-SH2 unit is structurally conserved between Abl and
      Src, leading to large conformational differences in their kinase domains. These
      differences help explain the ability of imatinib to preferentially inhibit Abl
      over Src.

PMID- 17513419
TI  - Aromatic L-amino acids activate the calcium-sensing receptor.
AB  - The calcium-sensing receptor (CaR) is recognized as a member of class 3 of the G
      protein coupled receptor superfamily. Members of this subgroup, which have large
      N-terminal extracellular domains, include receptors that respond specifically to
      the amino acid glutamate; receptors that respond to the glutamate analogue, gamma
      amino butyric acid; and several receptors that act as broad-spectrum amino acid
      sensors. The CaR is one of these broad-spectrum amino acid sensors that, along
      with several other members of the subgroup, also responds to extracellular Ca2+.
      In this mini-review, we consider evidence that the CaR is a sensor of aromatic
      amino acids, that it has broad-spectrum amino acid sensing properties, that it
      provides an amino acid binding site in its extracellular N-terminal Venus Fly
      Trap domain, and that amino acids have a physiological impact on systems in which
      the CaR is expressed.

PMID- 17513420
TI  - 3-Dimensional structures of G protein-coupled receptors and binding sites of
      agonists and antagonists.
AB  - We summarize here recent progress in predicting the 3-dimensional (3D) structure
      of G protein-coupled receptors (GPCR) and in predicting the binding sites for
      various agonists and antagonists. These receptors play a critical role in cell
      communications (dopamine, histamine, epinephrine, and serotonin) and in sensing
      the outside world (vision, smell, taste, and pain). There are no experimental 3D
      structures available for human GPCR despite their vital function and importance
      as therapeutic targets. Indeed, considering every form of life, there is an
      experimental structure for only 1 GPCR: bovine rhodopsin. Consequently, we
      developed the MembStruk method to predict the 3D structure without using
      homology. We then validated our predicted structures by using them to predict
      their binding sites and binding energies for strongly binding agonists and
      antagonists. The results were in excellent agreement with available binding and
      mutation experiments. We will summarize the results for adrenergic receptors,
      dopamine receptors, chemokine receptors, muscarinic acetylcholine receptors, and
      a tetrapeptide receptor (mas-related gene C11).

PMID- 17513421
TI  - Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain.
AB  - Aromatic amino acids in the brain function as precursors for the monoamine
      neurotransmitters serotonin (substrate tryptophan) and the catecholamines
      [dopamine, norepinephrine, epinephrine; substrate tyrosine (Tyr)]. Unlike almost
      all other neurotransmitter biosynthetic pathways, the rates of synthesis of
      serotonin and catecholamines in the brain are sensitive to local substrate
      concentrations, particularly in the ranges normally found in vivo. As a
      consequence, physiologic factors that influence brain pools of these amino acids,
      notably diet, influence their rates of conversion to neurotransmitter products,
      with functional consequences. This review focuses on Tyr and phenylalanine (Phe).
      Elevating brain Tyr concentrations stimulates catecholamine production, an effect
      exclusive to actively firing neurons. Increasing the amount of protein ingested,
      acutely (single meal) or chronically (intake over several days), raises brain Tyr
      concentrations and stimulates catecholamine synthesis. Phe, like Tyr, is a
      substrate for Tyr hydroxylase, the enzyme catalyzing the rate-limiting step in
      catecholamine synthesis. Tyr is the preferred substrate; consequently, unless Tyr
      concentrations are abnormally low, variations in Phe concentration do not affect
      catecholamine synthesis. Unlike Tyr, Phe does not demonstrate substrate
      inhibition. Hence, high concentrations of Phe do not inhibit catecholamine
      synthesis and probably are not responsible for the low production of
      catecholamines in subjects with phenylketonuria. Whereas neuronal catecholamine
      release varies directly with Tyr-induced changes in catecholamine synthesis, and
      brain functions linked pharmacologically to catecholamine neurons are predictably
      altered, the physiologic functions that utilize the link between Tyr supply and
      catecholamine synthesis/release are presently unknown. An attractive candidate is
      the passive monitoring of protein intake to influence protein-seeking behavior.

PMID- 17513423
TI  - An overview of phenylalanine and tyrosine kinetics in humans.
AB  - The initial use of a tracer of phenylalanine was by Moss and Schoenheimer in rats
      in 1940 to determine that phenylalanine was hydroxylated to tyrosine, defining
      for the first time the primacy of this pathway. Phenylalanine and tyrosine
      kinetics were not measured in humans until the 1970-80s. The first application
      was to determine the degree of blockage of phenylalanine hydroxylation in
      patients with hyperphenylalanemia and phenylketonuria, but this approach was
      expanded to determination of phenylalanine hydroxylation in normal subjects. Far
      more uses have been demonstrated for measuring rates of phenylalanine disposal
      and tyrosine production in relatively normal subjects than in patients with in
      born errors of metabolism. Key to use of tracers to determine phenylalanine and
      tyrosine metabolic rates has been the development of appropriate tracer models.
      Most applications have used relatively simple models ignoring the intracellular
      hydroxylation rate component. Because the liver is the primary site of
      hydroxylation in the body, the intracellular enrichment at the site of
      hydroxylation can be assessed from the tracer enrichments at isotopic steady
      state in rapid-turnover plasma proteins, such as Apo-B, made and secreted by the
      liver. Although there are potential problems with use of deuterated tracers of
      phenylalanine, suitable tracers are available and have been demonstrated for
      general measurement of phenylalanine and tyrosine kinetics in humans.

PMID- 17513424
TI  - Animal models of tyrosinemia.
AB  - Hereditary tyrosinemia I (HT I) is a genetic disorder of tyrosine metabolism
      characterized by progressive liver damage from infancy and by a high risk for
      hepatocellular carcinoma. HT I is due to mutations in the fumarylacetoacetate
      hydrolase (Fah) gene, which encodes the last enzyme in the tyrosine catabolic
      pathway. Disturbances in tyrosine metabolism lead to increased levels of
      succinylacetone and succinylacetoacetate. However, the mechanisms causing liver
      failure, cirrhosis, renal tubular dysfunction, and hepatocarcinoma are still
      unknown. Lethal albino deletion c14CoS mice and mice with target-disrupted Fah
      are models for HT I. They die in the perinatal period, although with a different
      phenotype from that seen in HT I in humans. In addition, 2 mouse strains that
      carry N-ethyl-N-nitrosourea-induced mutations in the Fah gene have been
      described. Mice with a splice mutation exhibit the milder features of the
      clinical phenotype. In mice that carry both Fah and 4-hydroxyphenylpyruvate
      dioxygenase gene mutations, administration of homogentisate results in rapid
      apoptosis of hepatocytes. Simultaneously, renal tubular epithelial cells are
      injured, resulting in Fanconi syndrome. These are central features of visceral
      injury in patients with HT I. Apoptosis of hepatocyte and renal tubular cells is
      prevented by the caspase inhibitors acetyl-Tyr-Val-Ala-Asp-CHO or acetyl-Asp-Glu
      Val-Asp-CHO. Apoptosis of hepatocytes and renal tubular epithelial cells are
      central features of this disease. Alterations in gene expression found in the
      liver of patients with HT I are responsible for the pathogenesis of this disease,
      for example, acute liver failure. Therefore, gene expression analysis allows a
      better understanding of the specific pathogenesis. Cell fusion of hematopoietic
      stem cells with hepatocytes leads to liver regeneration after liver injury. This
      finding was possible after using the liver injury model of HT I in Fah null mice.
      Thus, animal models of tyrosinemia are unique and useful tools to reveal
      mechanisms of interest to both clinical and basic science.

PMID- 17513425
TI  - Management of phenylketonuria and hyperphenylalaninemia.
AB  - Hyperphenylalaninemia (HPA) is the most frequently inherited disorder of amino
      acid metabolism (prevalence 1:10,000). In France, a nationwide neonatal screening
      was organized in 1978 to control its efficacy and patient follow-up.
      Phenylketonuria (PKU) was diagnosed in 81.6% of screened patients, the remaining
      affected with either non-PKU HPA (17.2%) or with cofactor deficiency (1.1%).
      French guidelines were established to specify the minimal diagnosis procedures
      and optimal treatment of patients. A low-phenylalanine diet must be started
      within the first days of life for all newborns whose blood phenylalanine levels
      are above 10 mg/dL (600 micromol/L). The dietary control must keep the
      phenylalanine levels between 2 and 5 mg/dL (120 and 300 micromol/L) until 10 y of
      age. Thereafter, a progressive and controlled relaxation of the diet is allowed,
      keeping levels below 15 mg/dL until the end of adolescence and below 20 mg/dL
      (1200 micromol/L) in adulthood. A lifelong follow-up is recommended for PKU women
      to prevent for maternal PKU.

PMID- 17513426
TI  - Response of phenylketonuria to tetrahydrobiopterin.
AB  - A favorable response, indicated by decline of blood phenylalanine (Phe) in
      patients with phenylketonuria (PKU), to orally administered 6-R-L-erythro-5, 6,
      7, 8-tetrahydrobiopterin (BH4) has been reported in many countries following the
      first publication in 1999. In this review, we describe the experience in the
      United States with PKU patients and their response to BH4. A significant response
      to BH4 is arbitrarily considered as a decrease of 30% or greater of blood Phe
      concentration 24 h after administration of BH4. In our studies, 18 of 37 patients
      with PKU (49%) responded to oral BH4 by >30% decrease in blood Phe concentration.
      Four PKU patients responded with a decrease of blood Phe concentration between
      17.3 and 26.3%. It is suggested that patients with sufficient response to BH4 are
      candidates who will benefit from BH4 as it becomes available for PKU management.
      In a separate trial, 20 patients with PKU were screened with ascending doses of
      BH4: 10, 20, and 40 mg/kg. A favorable response was found in 10 subjects (50%)
      after 10 mg/kg BH4 and 14 subjects (70%) after 20 mg/kg BH4. There was no
      additional advantage to 40 mg/kg BH4. A 1-wk trial with 10 and 20 mg/kg BH4 in
      the same 20 patients showed blood Phe concentrations lowest after 7 d of BH4. The
      BH4-responsive patients were genotyped and most were compound heterozygotes with
      1 mild mutation on 1 allele, responsible for the increase of the residual
      activity of Phe hydroxylase when BH4 was added. Individuals with the same
      genotype exhibit different responses upon administration of BH4, attributed to
      epigenetic factors, such as the metabolic makeup of the individual. Patients with
      PKU, regardless of their genotype or classification, need to be screened for
      response to BH4. The majority of patients are identified by 10 mg/kg BH4.

PMID- 17513427
TI  - Inherited disorders affecting dopamine and serotonin: critical neurotransmitters
      derived from aromatic amino acids.
AB  - Many inherited disorders affecting aromatic amino acid metabolism have been
      described. This review will concentrate on the defects that lead to deficiencies
      of dopamine and serotonin within the central nervous system. Phenylalanine
      hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase all require
      tetrahydrobiopterin (BH4) as a cofactor. Inherited defects that reduce the
      concentration of BH4, therefore, in general, lead to phenylketonuria and to
      deficiencies of dopamine and serotonin, as tyrosine hydroxylase and tryptophan
      hydroxylase are the rate-limiting enzymes required for the synthesis of these
      neurotransmitters. Primary inherited defects of tyrosine hydroxylase and aromatic
      l-amino acid decarboxylase have also been described. The clinical phenotypes are
      very similar to those observed in patients with defects of BH4 metabolism.
      Differential diagnosis is critical as treatment is different in each of the
      disorders. To date, a primary deficiency of tryptophan hydroxylase has not been
      described; when it finally is, the clinical phenotype might surprise us, as many
      groups around the world have been searching for such a defect for a long time.

PMID- 17513429
TI  - Aromatic amino acid requirements in healthy human subjects.
AB  - Dietary aromatic amino acids are needed to meet the requirements for
      phenylalanine and tyrosine for protein synthesis. The amounts needed for
      neurotransmitter synthesis and other biological processes are small and
      quantitatively negligible. The earlier nitrogen balance-based estimates were
      judged to be inadequate. Very recently, there have been 3 estimates published
      based on the indicator amino acid oxidation technique, which average 42 mg.kg(
      1).d(-1). This average value was obtained by feeding subjects a tyrosine-free
      diet and hence is an estimate of the mean maximum phenylalanine requirement. The
      mean minimum phenylalanine requirement estimate in the presence of an excess of
      tyrosine is 9.1 mg.kg(-1).d(-1). Hence, tyrosine can spare 78% of the dietary
      phenylalanine need. Finally the optimal proportions of dietary phenylalanine and
      tyrosine have been shown to be 60:40, respectively.

PMID- 17513430
TI  - Aromatic amino acid metabolism during liver failure.
AB  - Liver failure is associated with hepatic encephalopathy (HE). An imbalance in
      plasma levels of aromatic amino acids (AAA) phenylalanine, tyrosine, and
      tryptophan and branched chain amino acids (BCAA) and their BCAA/AAA ratio has
      been suggested to play a causal role in HE by enhanced brain AAA uptake and
      subsequently disturbed neurotransmission. Until recently, data on this subject
      and the role of the liver and splanchnic bed were scarce, particularly in humans,
      due to inaccessibility of portal and hepatic veins. Here, we discuss, against a
      background of relevant literature, data obtained in patients undergoing liver
      resection or with a transjugular intrahepatic portasystemic stent shunt (TIPSS),
      where these veins are accessible. The BCAA/AAA ratio remained unchanged after
      major liver resection, but plasma AAA levels were inversely correlated (P <
      0.001) with residual liver volume, in keeping with the observed hepatic AAA
      uptake. In patients with stable cirrhosis and a TIPSS, the plasma BCAA/AAA ratio
      was lower than in controls (1.19 +/- 0.09 vs. controls: 3.63 +/- 0.34).
      Gastrointestinal bleeding in cirrhotics with a TIPSS induced disturbances in BCAA
      levels and the BCAA/AAA ratio and induced catabolism, which could partly be
      corrected by isoleucine administration. AAA may be important in the pathogenesis
      of HE, but it is unlikely that they are the sole factors. HE most likely is a
      syndrome with multifactorial pathogenesis, where hyperammonemia, AAA/BCAA
      imbalances, inflammation, brain edema, and neurotransmitter changes interact.
      Novel therapies to normalize AAA levels in patients with liver failure (such as
      the molecular adsorbent recirculating system dialysis device) should probably be
      combined with supplementation of e.g. isoleucine and enhancing ammonia excretion
      by the kidneys.

PMID- 17513431
TI  - Phenylalanine and tyrosine metabolism in chronic kidney failure.
AB  - In chronic kidney failure, there is impairment in the conversion of phenylalanine
      to tyrosine. As a result, tyrosine and the tyrosine/phenylalanine ratio are
      reduced in plasma and many tissues, and phenylalanine concentrations tend to be
      normal or slightly increased. Although animal studies indicate that the kidney is
      not a major contributor to the conversion of phenylalanine to tyrosine, human
      studies conducted in the postabsorptive state suggest that the kidney plays a
      major role in the uptake of phenylalanine and its hydroxylation and release as
      tyrosine. The human splanchnic bed in the postabsorptive state also displays net
      uptake of both phenylalanine and tyrosine and hydroxylation of substantial
      amounts of phenylalanine to form tyrosine. In chronic renal failure (CRF)
      patients, splanchnic uptake of tyrosine appears to be reduced in the
      postabsorptive state. After an amino acid meal, there is net release of
      phenylalanine from the splanchnic bed in normal subjects and to an even greater
      degree in CRF patients; tyrosine is released postprandially in both normal
      subjects and CRF patients. In the postabsorptive state, tyrosine release from the
      kidney is largely derived from the hydroxylation of phenylalanine. In CRF, the
      release of tyrosine from the kidney is reduced and this reduction may be marked
      with advanced CRF. These observations, as well as isotope studies indicating
      normal phenylalanine flux, reduced tyrosine flux and impaired conversion of
      phenylalanine to tyrosine in CRF patients, raise the possibility that tyrosine
      may be an essential amino acid in this condition. Further research will be
      necessary to answer this question. Oxidative stress, which often increases in CRF
      patients, may lead to increased formation of chlorotyrosine and nitrotyrosine in
      plasma proteins and of nitrotyrosine in the brain. Increased nitrotyrosine is
      also found in kidneys of patients with diabetic nephropathy or allograft
      nephropathy. Increased serum concentrations of oxidation products of
      phenylalanine have also been observed in patients with CRF. Impaired urinary
      excretion also may lead to accumulation of metabolic products of both
      phenylalanine and tyrosine in CRF. It is not known whether the elevated protein
      chlorotyrosine or nitrotyrosine or increased oxidative products of phenylalanine
      cause adverse metabolic or toxic effects in patients with CRF.

PMID- 17513434
TI  - Lysine, arginine, and related amino acids: an introduction to the 6th amino acid
      assessment workshop.
AB  - The focus of the 6th workshop is on lysine, arginine, and related amino acids.
      Functions, metabolic pathways, clinical uses, and upper tolerance intakes are
      emphasized in the articles that follow. Lysine is arguably the most deficient
      amino acid in the food supply of countries where poverty exists, and since the
      discovery of the nitric oxide synthase pathway, arginine has come into prominence
      clinically because of the role of nitric oxide in cardiovascular physiology and
      pathophysiology.

PMID- 17513432
TI  - Specific amino acid dependency regulates the cellular behavior of melanoma.
AB  - Relative specific amino acid dependency is one of the metabolic abnormalities of
      melanoma cells and metabolic studies of this dependency are in their infancy.
      Herein, we review the current studies in this area and present new information
      that adds to the understanding of how tyrosine (Tyr) and phenylalanine (Phe)
      dependency as well as other amino acids regulate the cell behaviors of melanoma
      cells. Amino acid dependency of human melanoma cells is multifactorial and
      restricting Tyr and Phe to melanoma triggers a series of alterations in metabolic
      and signaling pathways in a time-ordered fashion to alter different cellular
      behaviors. For example, at early time points, the reduction of Tyr and Phe alters
      metabolic reactions quantitatively or qualitatively. The alterations include
      modulation of integrin/focal adhesion kinase (FAK)/G protein pathways and the
      plasminogen activator (PA)/PA inhibitor pathways to inhibit tumor cell invasion.
      At later time periods, a further drop in intracellular amino acids induces more
      metabolic alterations to impact the FAK/Ras/Raf and Bcl-2 pathways leading to
      apoptosis. The threshold effects and the targeting of multiple pathways by
      restriction of specific amino acids provide a connection between the metabolic
      alterations and signaling pathways that modulate the cellular behaviors of
      melanoma cells. Decoding the metabolic alterations that connect amino acid
      concentration to the crucial step(s) in signaling is important and an exciting
      area of cancer research.

PMID- 17513435
TI  - Arginine metabolism: boundaries of our knowledge.
AB  - Arginine has multiple metabolic fates and thus is one of the most versatile amino
      acids. Not only is it metabolically interconvertible with the amino acids proline
      and glutamate, but it also serves as a precursor for synthesis of protein, nitric
      oxide, creatine, polyamines, agmatine, and urea. These processes do not all occur
      within each cell but are differentially expressed according to cell type, age and
      developmental stage, diet, and state of health or disease. Arginine metabolism
      also is modulated by activities of various transporters that move arginine and
      its metabolites across the plasma and mitochondrial membranes. Moreover, several
      key enzymes in arginine metabolism are expressed as multiple isozymes whose
      expression can change rapidly and dramatically in response to a variety of
      different stimuli in health and disease. As illustrated by the questions raised
      in this article, we currently have an imperfect and incomplete picture of
      arginine metabolism for any mammalian species. It has become clear that a more
      complete understanding of arginine metabolism will require integration of
      information obtained from multiple approaches, including genomics, proteomics,
      and metabolomics.

PMID- 17513436
TI  - Unique aspects of lysine nutrition and metabolism.
AB  - Lysine nutrition is unique among indispensable amino acids in that it can be
      conserved and can be fed 12 h out of phase (delayed supplement) with the other
      dietary amino acids. In piglets, high levels (2-6%) of L-lysine added to a 10%
      protein diet can be tolerated without obvious detrimental effects. In both rat
      and piglet liver preparations, the first enzyme in the saccharopine-dependent
      pathway of lysine catabolism, lysine alpha-ketoglutarate reductase (LKR), is
      found only in the mitochondrial matrix. For Lys catabolism to occur, Lys must
      first enter the matrix of the mitochondrion. LKR, saccharopine dehydrogenase,
      mitochondrial lysine uptake, and lysine oxidation (LOX) all increased>3-fold in
      rats fed high levels of dietary protein (up to 60%). The activities of
      mitochondrial Lys uptake and LOX were similar when expressed as mmol/(d.100 g
      body weight). Thus, LOX can be a proxy for mitochondrial Lys uptake. Piglet liver
      LKR and LOX increase 5- to 10-fold when piglets are fed high-protein (50 or 75%)
      diets. In both the rat and piglet, after adapting to the high protein diet, the
      activity of LKR is 400-500 times that of LOX, suggesting that Lys uptake by a
      transporter(s) is rate limiting. Quantitative 24-h dietary infusion studies in
      piglets revealed that>80% of the Lys infused (4% of the diet) could not be
      recovered in the urine or body or accounted for by calculated Lys oxidation based
      on liver activity of LOX. Other pathways and tissues may account for the Lys
      oxidation in piglets.

PMID- 17513437
TI  - Regulation of nitric oxide synthesis and apoptosis by arginase and arginine
      recycling.
AB  - Nitric oxide (NO) is synthesized from arginine and O2 by NO synthase (NOS).
      Citrulline formed as a by-product of the NOS reaction can be recycled to arginine
      by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL). We found
      that AS and sometimes AL are coinduced with inducible NOS (iNOS) in various
      cells. In these cells, NO was synthesized from citrulline (via arginine) as well
      as from arginine, indicating operation of the citrulline-NO cycle. On the other
      hand, we found that arginase isoforms (types I and II) are coinduced with iNOS by
      LPS in rodent tissues and cultured macrophages. Km values for arginine of
      arginase I and II (approximately 10 mmol/L) are much higher than that of iNOS
      (approximately 5 micromol/L), whereas Vmax of arginase I and II were 10(3)-10(4)
      times higher than that of iNOS in activated macrophages. Thus, Vmax/Km values of
      arginases were close to that of iNOS, and these enzymes were expected to compete
      for arginine in the cells. In fact, NO production by iNOS in activated
      macrophages was decreased by coinduction of arginase I or arginase II. Low
      concentrations of NO protect cells from apoptosis, whereas excessive NO causes
      apoptosis. We found that NO causes endoplasmic reticulum (ER) stress, induces a
      transcription factor, CAAT/enhancer binding protein (C/EBP) homologous protein
      (CHOP), and leads to apoptosis. These results suggest that the arginine metabolic
      enzymes and the ER stress-CHOP pathway can be good targets to regulate NO
      production and NO-mediated apoptosis in diseases associated with overproduction
      or impaired production of NO.

PMID- 17513438
TI  - Citrulline: a new player in the control of nitrogen homeostasis.
AB  - Citrulline (CIT) is an amino acid that is not involved in protein synthesis but
      that is tightly linked to arginine (ARG) metabolism. CIT displays a very specific
      metabolism: In the 1980s, Windmuller demonstrated that the small intestine
      releases CIT, which is mainly taken up by the kidney and metabolized into ARG.
      Because CIT is not taken up by the liver, this ARG-CIT-ARG cycle can be seen as a
      means of protecting dietary ARG from liver degradation and of sustaining protein
      homeostasis. These observations have led to the concept that plasma CIT
      concentration would be a good marker of intestinal failure in short bowel
      syndrome. Hence, in massive intestinal resection, citrullinemia is greatly
      reduced, and this is proportional to the severity of the intestinal disease. This
      concept was then extended to other situations in which the intestinal function is
      compromised. The data strongly suggest that CIT may be a conditionally essential
      amino acid in situations where the intestinal function is compromised. Recent
      data support this idea. Thus, CIT supplementation is able to restore nitrogen
      balance, generate large amounts of ARG in rats with short bowel syndrome, and
      increase muscle protein content (+20%) as well as muscle protein synthesis (+90%)
      in elderly malnourished rats. Finally, recent data indicate that CIT per se could
      be able to stimulate muscle protein synthesis. Hence, CIT could play a pivotal
      role in maintaining protein homeostasis, and the determination of the underlying
      mechanisms involved in its action should be important for the development of new
      nutritional strategies in malnourished patients with compromised intestinal
      functions.

PMID- 17513439
TI  - Nutritional consequences of interspecies differences in arginine and lysine
      metabolism.
AB  - Differences in lysine and arginine requirements among various species such as
      omnivores (humans, pigs, rats, dogs), carnivores (cats), herbivores (rabbits,
      horses), ruminants (cattle), poultry, and fish, are covered in detail in this
      article. Although lysine is classified as an indispensable amino acid across
      species, the classification of arginine as either an indispensable or dispensable
      amino acid is more ambiguous because of differences among species in rates of de
      novo arginine synthesis. Because lysine is most often the limiting amino acid in
      the diet, its requirement has been extensively studied. By use of the ideal
      protein concept, the requirements of the other indispensable amino acids can be
      extrapolated from the lysine requirement. The successful use of this concept in
      pigs is compared with potential application of the ideal protein concept in
      humans. The current dietary arginine requirement varies widely among species,
      with ruminants, rabbits, and rats having relatively low requirements and
      carnivores, fish, and poultry having high requirements. Interspecies differences
      in metabolic arginine utilization and reasons for different rates of de novo
      arginine synthesis are reviewed in detail, as these are the primary determinants
      of the dietary arginine requirement. There is presently no dietary requirement
      for humans of any age, although this needs to be reassessed, particularly in
      neonates. A thorough understanding of the factors contributing to the lysine and
      arginine requirements in different species will be useful in our understanding of
      human amino acid requirements.

PMID- 17513440
TI  - Lysine requirement through the human life cycle.
AB  - Lysine cannot be synthesized by mammals and, as a consequence, is an
      indispensable amino acid. The main role of lysine is to participate in protein
      synthesis. The catabolism of lysine is principally located in the liver. Lysine
      released from digested protein undergoes a significant first-pass metabolism of
      approximately 30 to 42% in humans and piglets. An important question regarding
      the biological basis of the requirement of lysine is the possible participation
      of microbial de novo synthesized amino acids in the whole-body fluxes. Recent
      intake recommendations to meet the lysine requirement range from 64 to 30
      mg/(kg.d) for 0.5-y infants and adults (>18 y), respectively. Lysine intake in
      the Western human diet is in the range 40-180 mg/(kg.d). An upper limit of 300
      400 mg/(kg.d) can be considered in humans.

PMID- 17513441
TI  - Pharmacokinetics of arginine and related amino acids.
AB  - Arginine (ARG) and its related amino acids (AAs) ornithine (ORN) and citrulline
      (CIT) find a range of applications as dietary supplements in subgroups of healthy
      subjects (e.g., bodybuilders) and patients with acute or chronic malnutrition.
      These AAs appear to be well utilized in humans with, in general, a rapid return
      of blood concentrations to basal values (i.e., within 5-8 h) and low absolute and
      relative excretion in urine (<5% of administered dose). Based on published data
      for the maximum observed plasma concentrations (Cmax) after administration of
      doses in the range 5 to 10 g, CIT appeared to present relatively better
      absorption and systemic bioavailability than ARG and ORN. The few relevant dose
      ranging studies available include 1 limited to a single subject receiving 5- to
      20-g doses of ornithine alpha-ketoglutarate and another in which 8 subjects
      received from 5 to 15 g of CIT. Comparison of these 2 studies further indicates
      that CIT has higher bioavailability than ORN. The pharmacokinetics and metabolism
      of these AAs are modified by the coadministration of a salt such as alpha
      ketoglutarate that modifies AA metabolism, as has clearly been demonstrated for
      ornithine alpha-ketoglutarate. Concomitant administration of a meal leads to a 15
      to 30-min delay in Cmax. Finally, data from various pharmacokinetic studies
      together with basic physiology and biochemistry indicate that ARG is a net urea
      producer and ORN has a nitrogen-sparing effect, whereas CIT is neutral. However,
      most of the studies performed to date carry methodological weaknesses and are
      difficult to compare because of a number of confounding factors. To date, there
      have been no pharmacokinetic studies on the long-term administration of these AAs
      in healthy subjects despite the need to determine the safe upper limit of daily
      intake.

PMID- 17513442
TI  - The pharmacodynamics of L-arginine.
AB  - L-arginine is a precursor for nitric oxide (NO) synthesis. NO is a ubiquitous
      mediator that is formed by a family of enzymes named NO synthases. In the brain,
      NO acts as a neurotransmitter; in the immune system, NO acts as a mediator of
      host defense; and in the cardiovascular system, NO mediates the protective
      effects of the intact endothelium, acting as a vasodilator and endogenous
      antiatherogenic molecule. About 5 g of L-arginine is ingested each day in a
      normal Western diet. L-arginine plasma levels are not significantly reduced in
      most disease conditions, except end-stage renal failure during hemodialysis
      treatment. Nonetheless, intravenous or dietary (oral) administration of
      relatively large doses of L-arginine has been shown to result in enhanced NO
      formation in subjects with impaired endothelial function at baseline. In several
      controlled clinical trials, long-term administration of L-arginine has been shown
      to improve the symptoms of cardiovascular disease. However, in other trials L
      arginine was not beneficial, and in a recent study, the authors reported higher
      mortality of subjects receiving L-arginine than those receiving placebo. Recently
      it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a
      competitive inhibitor of L-arginine metabolism by NO synthase, may determine a
      subject's response to L-arginine supplementation. L-arginine appears to exert no
      effect in subjects with low ADMA levels, whereas in subjects with high ADMA
      levels, L-arginine restores the L-arginine/ADMA ratio to normal levels and
      thereby normalizes endothelial function. In conclusion, the effects of L-arginine
      supplementation on human physiology appear to be multicausal and dose-related.
      Doses of 3-8 g/d appear to be safe and not to cause acute pharmacologic effects
      in humans.

PMID- 17513443
TI  - Orotic acid excretion and arginine metabolism.
AB  - The urinary excretion of orotic acid, an intermediate in the pyrimidine
      biosynthetic pathway, is markedly increased in many inborn errors of the urea
      cycle and in a number of other disorders involving arginine metabolism. Carbamoyl
      phosphate, which accumulates within hepatic mitochondria in patients with
      ornithine transcarbamoylase deficiency, can diffuse to the cytosol and enter the
      pyrimidine pathway, resulting in greatly increased orotic acid production and
      excretion. This orotic aciduria also occurs in inborn errors of the mitochondrial
      ornithine/citrulline transporter, arginase, argininosuccinate synthetase, and
      argininosuccinate lyase. Increased orotic acid excretion is also found in a
      number of hypoargininemic states, such as lysinuric protein intolerance. However,
      orotic aciduria should not be used uncritically as an index of arginine
      deficiency because it is found in patients with arginase deficiency who exhibit
      hyperargininemia. Increased orotic acid excretion can also arise as a result of
      impairments of pyrimidine synthesis, whether brought about by a genetic defect
      (e.g., in UMP synthase) or by drugs that inhibit the terminal part of the pathway
      (e.g., allopurinol or 6-azauridine). When used appropriately, measurement of
      urinary orotic acid is a valuable tool for the study of many derangements of
      arginine metabolism, including arginine depletion, and to assess the efficacy of
      therapies used to replete this amino acid.

PMID- 17513444
TI  - Biomarkers of arginine and lysine excess.
AB  - Arginine supplementation is used in several disease states. In arginine-deficient
      states, supplementation is a logical choice of therapy. However, the definition
      of an arginine-deficient state is complex. For example, plasma arginine levels
      could be within normal range but intracellular arginine levels could be reduced
      because of membrane transport problems. Lysine competes with arginine for
      transport into the cell. In these situations, arginine supplementation of higher
      than required levels is proposed. Arginine has several important functions in
      metabolism as it is a precursor of metabolically active components such as nitric
      oxide (NO), ornithine, creatine, and polyamines. Supplementing arginine in excess
      could potentially overstimulate metabolism via enhanced production of NO. NO is a
      reactive component that, via production of radicals, will inactivate proteins. NO
      is also a powerful vasodilator, which could lead to severe hemodynamic
      instability. A good marker for excess supplementation of arginine or lysine could
      be an increased or reduced production rate of NO. However, NO production is
      difficult to measure because NO is a very labile component and is rapidly
      oxidized in blood. Stable isotope-labeled arginine and citrulline are used to
      trace the arginine-NO route. During supplementation of arginine in septic pigs or
      patients in septic shock, NO production, measured with stable isotope technology,
      is enhanced.

PMID- 17513445
TI  - Biomarkers identified in inborn errors for lysine, arginine, and ornithine.
AB  - Inborn errors of lysine, arginine, and ornithine metabolism are very rare: only a
      few patients affected with these disorders have been carefully investigated, and
      very few reports on long-term outcome are available. These rare data make it
      difficult to define safety limits of these amino acids and useful biomarkers from
      these disorders. Only 4 disorders give rise to an important increase of the
      plasma amino acid concentration proximal to the metabolic block: lysine in 2
      aminoadipic semialdehyde synthase deficiency, arginine in arginase deficiency,
      ornithine in ornithine amino transferase deficiency, and hyperammonemia
      hyperornithinemia homocitrullinuria syndrome. There is an obvious discrepancy
      between the important physiological role of these amino acids in cell metabolism
      and nutrition and the clinical consequences that are actually observed in these
      disorders.

PMID- 17513446
TI  - Pharmacokinetics and safety of arginine supplementation in animals.
AB  - Anticipating the future use of arginine to enhance fetal and neonatal growth as
      well as to treat diabetes and obesity, we performed studies in pigs, rats, and
      sheep to determine the pharmacokinetics of orally or i.v. administered arginine
      and the safety of its chronic supplementation. Our results indicate that all 3
      species rapidly catabolized the supplemental arginine. The elevated circulating
      concentrations of arginine generally returned to baseline levels within 4-5 h
      after administration, with the rates varying with the age and physiological
      status of the animals. The clearance of arginine was greater in pregnant than in
      nonpregnant animals, in young than in adult animals, in lean than in obese
      animals, and in type-1 diabetic than in nondiabetic animals. I.v. administration
      of arginine-HCl to pregnant ewes (at least 0.081 g arginine.kg body weight-1.d-1)
      did not result in any undesirable treatment-related effect. Neonatal pigs,
      growing-finishing pigs, pregnant pigs, and adult rats tolerated large amounts of
      chronic supplemental arginine (e.g. 0.62, 0.32, 0.21, and 2.14 g.kg body weight
      1.d-1, respectively) administered via enteral diets without the appearance of any
      adverse effect. On the basis of the comparative studies and a consideration of
      species differences in food intake per kilogram body weight, we estimate that a
      70-kg human subject should be able to tolerate long-term parenteral and enteral
      supplemental doses of 6 and 15 g/d arginine, respectively, in addition to a basal
      amount of arginine (4-6 g/d) from regular diets.

PMID- 17513447
TI  - Arginine and immunity.
AB  - For many years, dietary arginine supplementation, often combined with other
      substances, has been used as a mechanism to boost the immune system. Considerable
      controversy, however, exists as to the benefits and indications of dietary
      arginine due in part to a poor understanding of the role played by this amino
      acid in maintaining immune function. Emerging knowledge promises to clear this
      controversy and allow for arginine's safe use. In myeloid cells, arginine is
      mainly metabolized either by inducible nitric oxide (NO) synthases (iNOS) or by
      arginase 1, enzymes that are stimulated by T helper 1 or 2 cytokines,
      respectively. Thus, activation of iNOS or arginase (or both) reflects the type of
      inflammatory response in a specific disease process. Myeloid suppressor cells
      (MSC) expressing arginase have been described in trauma (in both mice and
      humans), intra-abdominal sepsis, certain infections, and prominently, cancer.
      Myeloid cells expressing arginase have been shown to accumulate in patients with
      cancer. Arginase 1 expression is also detected in mononuclear cells after trauma
      or surgery. MSC efficiently deplete arginine and generate ornithine. Through
      arginine depletion, MSC may control NO production and regulate other arginine
      dependent biological processes. Low circulating arginine has been documented in
      trauma and cancer, suggesting that MSC may exert a systemic effect and cause a
      state of arginine deficiency. Simultaneously, T lymphocytes depend on arginine
      for proliferation, zeta-chain peptide and T-cell receptor complex expression, and
      the development of memory. T-cells cocultured with MSC exhibit the molecular and
      functional effects associated with arginine deficiency. Not surprisingly, T-cell
      abnormalities, including decreased proliferation and loss of the zeta-chain, are
      observed in cancer and after trauma.

PMID- 17513448
TI  - Arginine in the critical care setting.
AB  - Arginine is a nonessential amino acid in the normal physiological state that
      becomes conditionally essential during periods of hypermetabolic stress. Recent
      literature supports the hypothesis that arginine plays an important role in the
      intermediary metabolism of the critically ill patient. Current critical care
      literature is conflicting on arginine use in the clinical setting, with some
      proposing it as a panacea, whereas others report it as poison. Multiple
      individual reports and at least 5 major meta-analyses using combinations of
      immune-modulating nutrients have reported mostly beneficial results, but few have
      evaluated the effects of arginine when given as a single supplemental nutrient.
      This review attempts to objectively analyze the literature and evaluate the
      potential role of arginine in the critical care setting.

PMID- 17513449
TI  - Adverse gastrointestinal effects of arginine and related amino acids.
AB  - Oral supplements of arginine and citrulline increase local nitric oxide (NO)
      production in the small intestine and this may be harmful under certain
      circumstances. Gastrointestinal toxicity was therefore reviewed with respect to
      the intestinal physiology of arginine, citrulline, ornithine, and cystine (which
      shares the same transporter) and the many clinical trials of supplements of the
      dibasic amino acids or N-acetylcysteine (NAC). The human intestinal dibasic amino
      acid transport system has high affinity and low capacity. L-arginine (but not
      lysine, ornithine, or D-arginine) induces water and electrolyte secretion that is
      mediated by NO, which acts as an absorbagogue at low levels and as a secretagogue
      at high levels. The action of many laxatives is NO mediated and there are reports
      of diarrhea following oral administration of arginine or ornithine. The clinical
      data cover a wide span of arginine intakes from 3 g/d to>100 g/d, but the
      standard of reporting adverse effects (e.g. nausea, vomiting, and diarrhea) was
      variable. Single doses of 3-6 g rarely provoked side effects and healthy athletes
      appeared to be more susceptible than diabetic patients to gastrointestinal
      symptoms at individual doses>9 g. This may relate to an effect of disease on
      gastrointestinal motility and pharmacokinetics. Most side effects of arginine and
      NAC occurred at single doses of >9 g in adults (>140 mg/kg) often when part of a
      daily regime of approximately>30 g/d (>174 mmol/d). In the case of arginine, this
      compares with the laxative threshold of the nonabsorbed disaccharide alcohol,
      lactitol (74 g or 194 mmol). Adverse effects seemed dependent on the dosage
      regime and disappeared if divided doses were ingested (unlike lactitol). Large
      single doses of poorly absorbed amino acids seem to provoke diarrhea. More
      research is needed to refine dosage strategies that reduce this phenomenon. It is
      suggested that dipeptide forms of arginine may meet this criterion.

PMID- 17513451
TI  - Glycosylation and annexin II cell surface translocation mediate airway epithelial
      wound repair.
AB  - Glycosylation of cell surface proteins can regulate multiple cellular functions.
      We hypothesized that glycosylation and expression of glycoproteins after
      epithelial injury is important in mediating repair. We report the use of an in
      vitro culture model of human airway epithelial cells (1HAEo(-)) to identify
      mediators of epithelial repair. We characterized carbohydrate moieties associated
      with repair by their interaction with the lectin from Cicer arietinum, chickpea
      agglutinin (CPA). Using CPA, we identified changes in cell surface glycosylation
      during wound repair. Following mechanical wounding of confluent monolayers of
      1HAEo(-) cells, CPA staining increases on the cell surface of groups of cells in
      proximity to the wound edge. Blocking the CPA carbohydrate ligand inhibited wound
      repair highlighting the role of the CPA carbohydrate ligand in epithelial repair.
      Annexin II (AII), a calcium-dependent, membrane-associated protein, was
      identified as a protein associated with the CPA ligand. By membrane protein
      biotinylation and immunodetection, we have shown that following mechanical
      wounding, the presentation of AII on the cell surface increases coordinate with
      repair. Cell surface AII accumulates in proximity to the wound. Furthermore,
      translocation of AII to the cell surface is N-glycosylation dependent. We are the
      first to demonstrate that following injury, N-glycosylation events and AII
      presentation on the cell surface of airway epithelial cells are important
      mediators in repair.

PMID- 17513452
TI  - Postpneumonectomy lung expansion elicits hypoxia-inducible factor-1alpha
      signaling.
AB  - We (42) previously reported differential regulation of hypoxia-inducible factors
      (HIF-1alpha, -2alpha, and -3alpha) mRNA in canine lungs during normal maturation
      and postpneumonectomy (PNX) compensatory growth in the absence of overt hypoxia.
      To test the hypothesis that lung expansion activates HIF signaling, we replaced
      the right lung of six adult foxhounds with inflated custom-shaped silicone
      prosthesis to keep the mediastinum in the midline and minimize lateral expansion
      of the remaining lung. After 3 wk of recovery and stabilization of perfusion, the
      prosthesis was acutely deflated in three animals, causing the remaining lung to
      expand by 114%. In three other animals, the prosthesis remained inflated. Three
      days following deflation, we observed significant elevation in the mRNA and
      nuclear protein levels of HIF-1alpha ( approximately 60%) as well as activation
      of its transcriptional regulator, the serine/threonine protein kinase B (phospho
      Akt-to-total Akt ratio, 124%), and the mRNA and protein levels of its downstream
      targets, erythropoietin receptor (71-183%) as well as VEGF (33-58%) compared with
      the pre-PNX control lung from the same animal. The mRNA of HIF-2alpha, HIF
      3alpha, and VEGF receptors did not change with acute deflation. We conclude that
      in vivo lung expansion by post-PNX deflation of space-occupying prosthesis
      elicits coordinated activation of HIF-1alpha signaling in adult lungs. This
      pathway could play an important role in mediating lung growth and remodeling
      during maturation and post-PNX compensation.

PMID- 17513453
TI  - The role of alpha-, beta-, and gamma-ENaC subunits in distal lung epithelial
      fluid absorption induced by pulmonary edema fluid.
AB  - Edema fluid (EF) increases epithelial Na(+) transport by rat fetal distal lung
      epithelia (FDLE) and induces net lung fluid absorption in fetal mouse lung
      explants [Rafii B, Gillie DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G,
      Barker PM, O'Brodovich H. J Physiol (Lond) 544: 537-548, 2002]. We now show that
      EF increases fluid absorption across monolayers of rat FDLE in a dose-dependent
      manner. To study the role of subunits of the epithelial Na(+) channel (ENaC) in
      the phenomena, we cultured explants from the distal lungs of 16-day gestational
      age wild-type (WT) or alpha-, beta-, or gamma-ENaC knockout or heterozygote (HT)
      mice. WT explants cultured in media continuously expanded over time as a result
      of net fluid secretion. In contrast, when explants were exposed to EF for 24 h,
      net fluid absorption occurred. EF-exposed explants had normal histology, but
      marked changes were seen after Triton X-100 or staurosporine exposure.
      Transmission electron microscopy showed EF promoted lamellar body formation and
      abundant surfactant in the explants' lumens. EF-induced changes in explant size
      were similar in alpha-ENaC knockout, WT, and HT littermate fetal lung explants (P
      > 0.05). In contrast, EF's effect was attenuated in beta- and gamma-ENaC
      knockouts (P < 0.05) vs. WT and HT littermate fetal lung explants. EF exposure
      slightly decreased or had no effect on mRNA levels for alpha-ENaC in various
      mouse genotypes but decreased expression of beta- and gamma-ENaC subunit mRNAs (P
      < 0.01) across all genotype groups. We conclude that beta- and gamma-, but not
      alpha-, ENaC subunits are essential for EF to exert its maximal effect on net
      fluid absorption by distal lung epithelia.

PMID- 17513454
TI  - A role for neural pathways in adenosine-induced bronchoconstriction.

PMID- 17513455
TI  - Anti-IL-8 autoantibody:IL-8 immune complexes suppress spontaneous apoptosis of
      neutrophils.
AB  - Our previous studies demonstrated that a significant fraction of interleukin-8
      (IL-8) in lung fluids from patients with acute lung injury (ALI) and the acute
      respiratory distress syndrome (ARDS) is associated with anti-IL-8 autoantibodies
      (anti-IL-8:IL-8 immune complexes). Neutrophils have been implicated in the
      pathogenesis of ALI/ARDS, and moreover, it is well-established that apoptosis of
      neutrophils is delayed in patients with ALI/ARDS. The aim of this study was,
      therefore, to examine the role of anti-IL-8:IL-8 immune complexes in modulating
      spontaneous apoptosis of normal human neutrophils. Apoptosis was assessed by
      evaluating morphological changes, measuring enzymatic activity of caspase-3, and
      determining the extent of DNA degradation. We found that samples containing anti
      IL-8:IL-8 immune complexes but not samples from which these complexes were
      removed inhibited neutrophil apoptosis. Furthermore, the former samples or
      effectively anti-IL-8:IL-8 complexes induced an increase in the level of
      antiapoptotic protein, Bcl-X(L). In contrast, levels of proapoptotic proteins Bax
      and Bak were decreased in the same conditions. Activity of both caspase-3 and
      caspase-9 was also suppressed by anti-IL-8:IL-8 complex-containing samples.
      Finally, we established that IgG receptor, FcgammaRIIa, mediates antiapoptotic
      activity of anti-IL-8:IL-8 complexes and that the key components of the
      FcgammaRIIa signaling pathway, Src, Syk, PI3 kinase, and ERK, may be involved in
      regulation of neutrophil apoptosis by the complexes. These studies demonstrate
      for the first time that anti-IL-8:IL-8 immune complexes have the ability to
      prolong neutrophil life.

PMID- 17513456
TI  - Constitutive and inducible thymic stromal lymphopoietin expression in human
      airway smooth muscle cells: role in chronic obstructive pulmonary disease.
AB  - Thymic stromal lymphopoietin (TSLP) is a novel cytokine that triggers dendritic
      cell-mediated T helper (Th)-2 inflammatory responses. Previous studies have
      demonstrated that human airway smooth muscle cells (HASMC) play a critical role
      in initiating or perpetuating airway inflammation by producing chemokines and
      cytokines. In this study, we first evaluated the expression of TSLP in primary
      HASMC and investigated how proinflammatory cytokines (TNF-alpha and IL-1beta) and
      Th-2 cytokines (IL-4, IL-9) regulate TSLP production from HASMC. TSLP mRNA and
      protein were assessed by real-time RT-PCR, ELISA, and immunofluorescence from
      primary HASMC cultures. Primary HASMC express constitutive level of TSLP.
      Incubation of HASMC with IL-1 or TNF-alpha resulted in a significant increase of
      TSLP mRNA and protein release from HASMC. Furthermore, combination of IL-1beta
      and TNF-alpha has an additive effect on TSLP release by HASMC. Primary HASMC
      pretreated with inhibitors of p38 or p42/p44 ERK MAPK, but not
      phosphatidylinositol 3-kinase, showed a significant decrease in TSLP release on
      IL-1beta and TNF-alpha treatment. Furthermore, TSLP immunoreactivity was present
      in ASM bundle from chronic obstructive pulmonary disease (COPD) and to lesser
      degree in normal subjects. Taken together, our data provide the first evidence of
      IL-1beta- and TNF-alpha-induced TSLP expression in HASMC via (p38, p42/p44) MAPK
      signaling pathways. Our results raise the possibility that HASMC may play a role
      in COPD airway inflammation via TSLP-dependent pathway.

PMID- 17513457
TI  - Paxillin-beta-catenin interactions are involved in Rac/Cdc42-mediated endothelial
      barrier-protective response to oxidized phospholipids.
AB  - Oxidized phospholipids may appear in the pulmonary circulation as a result of
      acute lung injury or inflammation. We have previously described barrier
      protective effects of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3
      phosphocholine (OxPAPC) on human pulmonary endothelial cells (EC) mediated by
      small GTPases Rac and Cdc42. This work examined OxPAPC-induced focal adhesion
      (FA) and adherens junction (AJ) remodeling and potential interactions between FA
      and AJ protein complexes involved in OxPAPC-induced EC barrier enhancement.
      Immunofluorescence analysis, subcellular fractionation, and coimmunoprecipitation
      assays have shown that OxPAPC induced translocation and peripheral accumulation
      of FA complexes containing paxillin, focal adhesion kinase, vinculin, GIT1, and
      GIT2, increased association of AJ proteins vascular endothelial-cadherin, p120
      catenin, alpha-, beta-, and gamma-catenins, and dramatically enhanced cell
      junction areas covered by AJ. Coimmunoprecipitation, pulldown assays, and
      confocal microscopy studies have demonstrated that OxPAPC promoted novel
      interactions between FA and AJ complexes via paxillin and beta-catenin
      association, which was critically dependent on Rac and Cdc42 activities and was
      abolished by pharmacological or small interfering RNA (siRNA)-mediated inhibition
      of Rac and Cdc42. Depletion of beta-catenin using the siRNA approach attenuated
      OxPAPC-induced paxillin translocation to the cell periphery, but also
      significantly decreased interaction of paxillin with AJ protein complex. In turn,
      paxillin knockdown by specific siRNA attenuated AJ enhancement in response to
      OxPAPC. These results show for the first time the novel interactions between FA
      and AJ protein complexes critical for EC barrier regulation by OxPAPC.

PMID- 17513458
TI  - Endotoxin-induced maturation of monocytes in preterm fetal sheep lung.
AB  - The fetal lung normally contains immature monocytes and very few mature
      macrophages. The chorioamnionitis frequently associated with preterm birth
      induces monocyte influx into the fetal lung. Previous studies demonstrated that
      monocytes in the developing lung can mediate lung injury responses that resemble
      BPD in humans. We hypothesized that chorioamnionitis would induce maturation of
      immature monocytes in the fetal lung. Groups of three to seven time-mated ewes
      received saline or 10 mg of endotoxin (Escherichia coli 055:B5) in saline by
      intra-amniotic injection for intervals from 1 to 14 days before operative
      delivery at 124 days of gestational age. Monocytic cells from lung tissue were
      recovered using Percoll gradients. Monocytic cells consistent with macrophages
      were identified morphologically and by myosin heavy chain class II expression. An
      increase in macrophages was preceded by induction of granulocyte-macrophage
      colony-stimulating factor in the lung and subsequent activation of the
      transcription factor PU.1. The production of IL-6 by monocytes/macrophages in
      response to endotoxin challenge in vitro increased 7 and 14 days after exposure
      to intra-amniotic endotoxin. Recombinant TNF-alpha induced IL-6 production by
      lung monocytic cells exposed to intra-amniotic endotoxin but not in control
      cells. Monocytic phagocytosis of apoptotic neutrophils also increased 7 and 14
      days after exposure to intra-amniotic endotoxin. Intra-amniotic endotoxin induced
      lung monocytes to develop into functionally mature cells consistent with
      macrophages. These findings have implications for lung immune responses after
      exposure to chorioamnionitis.

PMID- 17513459
TI  - Molecular mechanisms of light stress of photosynthesis.
AB  - Photosynthesis is the basic energy conversion process on Earth, which makes
      possible the utilization of the energy of sunlight for living organisms. However,
      light is not only the basic driving force of photosynthesis, but also an
      important stress factor at the same time. Light-induced decline of photosynthetic
      activity, generally denoted as photoinhibition, is a general phenomenon in all
      oxygenic photosynthetic organism under conditions when the metabolic processes
      cannot keep up with the electron flow produced by the primary photoreactions.
      Although light-induced damage occurs in all pigmented photosynthetic complexes
      the primary site of photoinhibition is the photosystem II (PSII) complex, which
      performs light-driven oxidation of water to protons and oxygen. The main factors,
      which are responsible for the light sensitivity of photosystem II, are excited
      pigment molecules, oxygen, manganese, as well as electron donors with high
      oxidizing potential. Photosystem II can be efficiently protected from photodamage
      by the combination of harmless dissipation of absorbed light energy, nonradiative
      charge recombination, and repair of damaged reaction center complexes, making
      possible the safe utilization of light, the highly energetic substrate of
      photosynthesis.

PMID- 17513460
TI  - New tricks for an old dog: the evolving world of Hsp70.
AB  - The Hsp70 chaperone is arguably the most studied member of the heat shock protein
      family, a legacy traced back to the early days of phage genetics. However, much
      still remains to be learned about this essential protein-folding machine. Its
      involvement in a number of human pathologies, ranging from cancer to protein
      aggregation diseases, underscores the need for a comprehensive understanding of
      the myriad cellular roles Hsp70 plays and the outstanding open questions. This
      article will explore several exciting avenues of research into the function and
      biology of the chaperone. Analysis of the many eukaryotic Hsp70 isoforms has
      demonstrated distinct functional roles for some Hsp70 members, to the point of
      transition from a protein "foldase" to a chaperone cofactor. New insights gained
      from structural studies have unveiled a likely model for interdomain
      communication and thus regulation of substrate binding and processing. Advances
      in small molecule modulation of Hsp70 activity are likely to have significant
      clinical impact. There is also a growing realization that Hsp70 participates in
      distinct functional networks in partnership with other protein chaperones. The
      field is thus at an exciting time when the substantial successes of the past have
      provided a solid framework that will be used to fuel both discovery and
      application--Hsp70, from molecule to man.

PMID- 17513461
TI  - Metabolic syndrome: psychosocial, neuroendocrine, and classical risk factors in
      type 2 diabetes.
AB  - This article summarizes some aspects of stress in the metabolic syndrome at the
      psychosocial, tissue, and cellular levels. The metabolic syndrome is a valuable
      research concept for studying population health and social-biological
      translation. The cluster of cardiovascular risk factors labeled the metabolic
      syndrome is linked with low socioeconomic status. Systematic differences in diet
      and physical activity contribute to social patterning of the syndrome. In
      addition, psychosocial factors including chronic work stress are linked with its
      development. Psychosocial factors could lead to metabolic perturbations and
      increase cardiovascular risk via activation of neuroendocrine responses, for
      example, in the autonomic nervous system and in several hormonal pathways. High
      glucocorticoid levels will promote lipid storage in visceral rather than
      subcutaneous adipose tissue. Adipocytes secrete several proinflammatory
      cytokines, which considered major contributors to increase in oxidants and cell
      injury. Upregulation of heme oxygenase 1 (HO-1) and peroxidase in the early
      development of diabetes produces a decrease in oxidative-mediated injury.
      Increased HO activity is associated with a significant decrease in superoxide,
      endothelial cell shedding and blood pressure. Finally, it is proposed that
      overexpression of glutathione peroxidase in beta cells may protect beta cell
      deterioration from oxidative stress during development of diabetes and
      hyperglycemia and this may result in attenuation of beta cell failure. If this
      proves to be the case, then the scene will be set to develop glutathione
      peroxidase mimetics for use in preclinical and clinical trials.

PMID- 17513462
TI  - Glucocorticoid hyper- and hypofunction: stress effects on cognition and
      aggression.
AB  - It is now well documented that both increased and decreased stress responses can
      profoundly affect cognition and behavior. This mini review presents possible
      neural mechanisms subserving stress effects on memory and aggression,
      particularly focusing on glucocorticoid (GC) hyper- and hypofunction. First,
      uncontrollable stress impedes hippocampal memory and long-term potentiation
      (LTP). Because the hippocampus is important for the stability of long-term memory
      and because LTP has qualities desirable of an information storage mechanism, it
      has been hypothesized that stress-induced alterations in LTP contribute to memory
      impairments. Recent evidence suggests a neural-endocrine network comprising
      amygdala, prefrontal cortex (PFC), and glucocorticoids may be involved in
      regulating stress effects on hippocampal mnemonic functioning. Second, antisocial
      aggressiveness correlates with chronically decreased glucocorticoid production,
      and this condition leads in rats to behavioral-autonomic deficits reminiscent of
      the human disorder. Glucocorticoid deficiency-induced antisocial aggressiveness
      results from functional changes in the PFC, medial and central amygdala, and
      altered serotonin and substance P neurotransmissions. Accordingly, a
      neurobiological understanding of how stress and glucocorticoid deficiency alter
      brain, cognition, and behavior is an important challenge facing modern
      neuroscience with broad implications for individual and social well-being.

PMID- 17513463
TI  - Amphotericin B and coccidioidomycosis.
AB  - Prior to the 1950s no effective therapy for coccidioidomycosis existed. The
      advent of amphotericin B ushered in the therapeutic era for coccidioidomycosis.
      Until this time amphotericin B and its lipid congeners have been regarded as the
      "gold standard" of therapy for severe pulmonary and disseminated
      coccidioidomycosis. The availability of azoles and later triazoles for the past
      three decades have relegated the amphotericins into a rescue mode, used mainly in
      widely disseminated cases, azole intolerance, or when there are contraindications
      to Azoles, such as pregnancy. In meningitis the intrathecal use of amphotericin B
      is still used frequently by some clinicians alone or with a triazole. The newer
      lipid preparations, while more expensive, have significantly reduced toxicity,
      particularly nephropathy.

PMID- 17513464
TI  - Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of
      oncogene addiction and tumor stress.
AB  - The molecular chaperone HSP90 has emerged as an exciting target for cancer
      treatment. We review the potential advantages of HSP90 inhibitors, particularly
      the simultaneous combinatorial depletion of multiple oncogenic "client" proteins,
      leading to blockade of many cancer-causing pathways and the antagonism of all of
      the hallmark pathological traits of malignancy. Cancer selectivity is achieved by
      exploiting cancer "dependencies," including oncogene addiction and the stressed
      state of malignant cells. The multiple downstream effects of HSP90 inhibitors
      should make the development of resistance more difficult than with agents having
      more restricted effects. We review the various classes of HSP90 inhibitor that
      have been developed, including the natural products geldanamycin and radicicol
      and also the purine scaffold and pyrazole/isoxazole class of synthetic small
      molecule inhibitors. A first-in-class HSP90 drug, the geldanamycin analog 17-AAG,
      has provided proof of concept for HSP90 inhibition in patients at well tolerated
      doses and therapeutic activity has been seen. Other inhibitors show promise in
      preclinical and clinical development. Opportunities and challenges for HSP90
      inhibitors are discussed, including use in combination with other agents. Most of
      the current HSP90 inhibitors act by blocking the essential nucleotide binding and
      ATPase activity required for chaperone function. Potential new approaches are
      discussed, for example, interference with cochaperone binding and function in the
      superchaperone complex. Biomarkers for use with HSP90 inhibitors are described.
      We stress how basic and translational research has been mutually beneficial and
      indicate future directions to enhance our understanding of molecular chaperones
      and their exploitation in cancer and other diseases.

PMID- 17513465
TI  - Public health surveillance for coccidioidomycosis in Arizona.
AB  - Coccidioidomycosis or Valley Fever is a fungal disease that occurs primarily in
      the southwestern United States. Of the estimated 150,000 U. S. coccidioidomycosis
      infections per year, approximately 60% occur in Arizona, making this state the
      focal point for investigation of the disease. In this manuscript, we describe the
      epidemiology of coccidioidomycosis reported in Arizona over the last decade,
      hypotheses for the findings, and Arizona's response to the rising epidemic.
      Coccidioidomycosis surveillance data in Arizona consist of basic demographics of
      all laboratory and physician-diagnosed cases, the reporting of which has been
      mandated by law since 1997. The rate of reported coccidioidomycosis has more than
      quadrupled over the last decade from 21 cases per 100,000 population in 1997 to
      91 cases per 100,000 in 2006 (P < 0.001). Case rates in older age groups (>/=65
      years old) have more than doubled since 2000 (P < 0.001). These data demonstrate
      the rising coccidioidomycosis epidemic in Arizona, especially among the elderly.
      The increase in the numbers of reported cases can be partially explained by the
      institution of mandatory laboratory reporting in 1997, but the cause of the
      persistent rise after 1999 is unknown. Further investigation of
      coccidioidomycosis will not only assist with the development of public health
      interventions to control this disease in Arizona and the southwestern United
      States, but will also provide important information to prepare for a bioterrorism
      event caused by this select agent.

PMID- 17513466
TI  - Virulence mechanisms of coccidioides.
AB  - Coccidioides is a fungal respiratory pathogen of humans that can cause disease in
      both immunosuppressed and immunocompetent individuals. We describe here three
      mechanisms by which the pathogen survives in the hostile host environment:
      production of a dominant spherule outer wall glycoprotein (SOWgp) that modulates
      host immune response and results in compromised cell-mediated immunity to
      coccidioidal infection, depletion of SOWgp presentation on the surface of
      endospores, which prevents host recognition of the pathogen when the fungal cells
      are most vulnerable to phagocytic defenses, and induction of elevated production
      of host arginase I and coccidioidal urease, which contribute to tissue damage at
      sites of infection. Arginase I competes with inducible nitric oxide synthase
      (iNOS) in macrophages for the common substrate, L-arginine, and thereby reduces
      nitric oxide (NO) production and increases the synthesis of host orinithine and
      urea. Host-derived L-ornithine may promote pathogen growth and proliferation by
      providing a pool of the monoamine, which could be taken up and used for synthesis
      of polyamines via metabolic pathways of the parasitic cells. We have shown that
      high concentrations of Coccidioides- and host-derived urea at infection sites in
      the presence of urease produced and released by the pathogen, results in
      secretion of ammonia and contributes to alkalinization of the microenvironment.
      We propose that ammonia and enzymatically active urease released from spherules
      during the parasitic cycle of Coccidioides exacerbate the severity of
      coccidioidal infection by contributing to a compromised immune response to
      infection and damage of host tissue at foci of infection.

PMID- 17513467
TI  - Compensability of, and legal issues related to, coccidioidomycosis.
AB  - Legal issues that may develop when treating patients with coccidioidomycosis
      include allegations of medical malpractice, claims for workers' compensation
      benefits, and civil actions against business owners. In states where the disease
      is most prevalent, California recognizes cocci diodomycosis as a compensable
      condition, although Arizona does not. In civil actions, the state courts have not
      imposed liability on any business or institution for those that claim to have
      developed cocci diodomycosis on or near the premises of the business.

PMID- 17513469
TI  - Multicellular development in Myxococcus xanthus is stimulated by predator-prey
      interactions.
AB  - Myxococcus xanthus is a predatory bacterium that exhibits complex social
      behavior. The most pronounced behavior is the aggregation of cells into raised
      fruiting body structures in which cells differentiate into stress-resistant
      spores. In the laboratory, monocultures of M. xanthus at a very high density will
      reproducibly induce hundreds of randomly localized fruiting bodies when exposed
      to low nutrient availability and a solid surface. In this report, we analyze how
      M. xanthus fruiting body development proceeds in a coculture with suitable prey.
      Our analysis indicates that when prey bacteria are provided as a nutrient source,
      fruiting body aggregation is more organized, such that fruiting bodies form
      specifically after a step-down or loss of prey availability, whereas a step-up in
      prey availability inhibits fruiting body formation. This localization of
      aggregates occurs independently of the basal nutrient levels tested, indicating
      that starvation is not required for this process. Analysis of early developmental
      signaling relA and asgD mutants indicates that they are capable of forming
      fruiting body aggregates in the presence of prey, demonstrating that the
      stringent response and A-signal production are surprisingly not required for the
      initiation of fruiting behavior. However, these strains are still defective in
      differentiating to spores. We conclude that fruiting body formation does not
      occur exclusively in response to starvation and propose an alternative model in
      which multicellular development is driven by the interactions between M. xanthus
      cells and their cognate prey.

PMID- 17513468
TI  - PdhR (pyruvate dehydrogenase complex regulator) controls the respiratory electron
      transport system in Escherichia coli.
AB  - The pyruvate dehydrogenase (PDH) multienzyme complex plays a key role in the
      metabolic interconnection between glycolysis and the citric acid cycle.
      Transcription of the Escherichia coli genes for all three components of the PDH
      complex in the pdhR-aceEF-lpdA operon is repressed by the pyruvate-sensing PdhR,
      a GntR family transcription regulator, and derepressed by pyruvate. After a
      systematic search for the regulation targets of PdhR using genomic systematic
      evolution of ligands by exponential enrichment (SELEX), we have identified two
      novel targets, ndh, encoding NADH dehydrogenase II, and cyoABCDE, encoding the
      cytochrome bo-type oxidase, both together forming the pathway of respiratory
      electron transport downstream from the PDH cycle. PDH generates NADH, while Ndh
      and CyoABCDE together transport electrons from NADH to oxygen. Using gel shift
      and DNase I footprinting assays, the PdhR-binding site (PdhR box) was defined,
      which includes a palindromic consensus sequence, ATTGGTNNNACCAAT. The binding in
      vitro of PdhR to the PdhR box decreased in the presence of pyruvate. Promoter
      assays in vivo using a two-fluorescent-protein vector also indicated that the
      newly identified operons are repressed by PdhR and derepressed by the addition of
      pyruvate. Taken together, we propose that PdhR is a master regulator for
      controlling the formation of not only the PDH complex but also the respiratory
      electron transport system.

PMID- 17513470
TI  - complex interplay between type 1 fimbrial expression and flagellum-mediated
      motility of uropathogenic Escherichia coli.
AB  - Type 1 fimbriae and flagella have been previously shown to contribute to the
      virulence of uropathogenic Escherichia coli (UPEC) within the urinary tract. In
      this study, the relationship between motility and type 1 fimbrial expression was
      tested for UPEC strain CFT073 by examining the phenotypic effect of fimbrial
      expression on motility and the effect that induction of motility has on type 1
      fimbrial expression. While constitutive expression of type 1 fimbriae resulted in
      a significant decrease in motility and flagellin expression (P < 0.0001), a loss
      of type 1 fimbrial expression did not result in increased motility. Additionally,
      hypermotility and flagellar gene over- and underexpression were not observed to
      affect the expression of type 1 fimbriae. Hence, it appeared that the
      relationship between type 1 fimbrial expression and motility is unidirectional,
      where the overexpression of type 1 fimbriae dramatically affects motility and
      flagellum expression but not vice versa. Moreover, the constitutive expression of
      type 1 fimbriae in UPEC cystitis isolate F11 and the laboratory strain E. coli K
      12 MG1655 also resulted in decreased motility, suggesting that this phenomenon is
      not specific to CFT073 or UPEC in general. Lastly, by analyzing the repression of
      motility caused by constitutive type 1 fimbrial expression, it was concluded that
      the synthesis and presence of type 1 fimbriae at the bacterial surface is only
      partially responsible for the repression of motility, as evidenced by the partial
      restoration of motility in the CFT073 fim L-ON DeltafimAICDFGH mutant.
      Altogether, these data provide further insight into the complex interplay between
      type 1 fimbrial expression and flagellum-mediated motility.

PMID- 17513471
TI  - FtsZ directs a second mode of peptidoglycan synthesis in Escherichia coli.
AB  - Certain penicillin binding protein mutants of Escherichia coli grow with
      spirillum-like morphologies when the FtsZ protein is inhibited, suggesting that
      FtsZ might govern aspects of cell wall growth other than those strictly
      associated with septation. While investigating the mechanism of spiral cell
      formation, we discovered conditions for visualizing this second function of FtsZ.
      Normally, inhibiting the cytoskeleton protein MreB forces E. coli cells to grow
      as smoothly enlarging spheres from which the poles disappear, yielding coccoid or
      lemon-shaped forms. However, when FtsZ and MreB were inhibited simultaneously in
      a strain lacking PBP 5 and PBP 7, the resulting cells ballooned outward but
      retained conspicuous rod-shaped extensions at sites representing the original
      poles. This visual phenotype was paralleled by the biochemistry of sacculus
      growth. Muropeptides are usually inserted homogeneously into the lateral cell
      walls, but when FtsZ polymerization was inhibited, the incorporation of new
      material occurred mainly in the central regions of cells and was significantly
      lower in those portions of side walls abutting a pole. Thus, reduced precursor
      incorporation into side walls near the poles explained why these regions retained
      their rod-like morphology while the rest of the cell grew spherically. Also,
      inhibiting FtsZ increased the amount of pentapeptides in sacculi by about one
      third. Finally, the MreB protein directed the helical or diagonal incorporation
      of new peptidoglycan into the wall, but the location of that incorporation
      depended on whether FtsZ was active. In sum, the results indicate that in
      addition to nucleating cell septation in E. coli, FtsZ can direct the insertion
      of new peptidoglycan into portions of the lateral wall.

PMID- 17513472
TI  - Type IV fimbrial biogenesis is required for protease secretion and natural
      transformation in Dichelobacter nodosus.
AB  - The objective of this study was to develop an understanding of the molecular
      mechanisms by which type IV fimbrial biogenesis, natural transformation, and
      protease secretion are linked in the ovine foot rot pathogen, Dichelobacter
      nodosus. We have shown that like the D. nodosus fimbrial subunit FimA, the pilin
      like protein PilE and the FimN, FimO, and FimP proteins, which are homologs of
      PilB, PilC, and PilD from Pseudomonas aeruginosa, are essential for fimbrial
      biogenesis and natural transformation, indicating that transformation requires an
      intact type IV fimbrial apparatus. The results also showed that extracellular
      protease secretion in the fimN, fimO, fimP, and pilE mutants was significantly
      reduced, which represents the first time that PilB, PilC, and PilE homologs have
      been shown to be required for the secretion of unrelated extracellular proteins
      in a type IV fimbriate bacterium. Quantitative real-time PCR analysis of the
      three extracellular protease genes aprV2, aprV5, and bprV showed that the effects
      on protease secretion were not mediated at the transcriptional level.
      Bioinformatic analysis did not identify a classical type II secretion system, and
      the putative fimbrial biogenesis gene pilQ was the only outer membrane secretin
      gene identified. Based on these results, it is postulated that in D. nodosus,
      protease secretion occurs by a type II secretion-related process that directly
      involves components of the type IV fimbrial biogenesis machinery, which
      represents the only type II secretion system encoded by the small genome of this
      highly evolved pathogen.

PMID- 17513473
TI  - Phosphorylated AbsA2 negatively regulates antibiotic production in Streptomyces
      coelicolor through interactions with pathway-specific regulatory gene promoters.
AB  - The AbsA two-component signal transduction system, comprised of the sensor kinase
      AbsA1 and the response regulator AbsA2, acts as a negative regulator of
      antibiotic production in Streptomyces coelicolor, for which the phosphorylated
      form of AbsA2 (AbsA2 approximately P) is the agent of repression. In this study,
      we used chromatin immunoprecipitation to show that AbsA2 binds the promoter
      regions of actII-ORF4, cdaR, and redZ, which encode pathway-specific activators
      for actinorhodin, calcium-dependent antibiotic, and undecylprodigiosin,
      respectively. We confirm that these interactions also occur in vitro and that the
      binding of AbsA2 to each gene is enhanced by phosphorylation. Induced expression
      of actII-ORF4 and redZ in the hyperrepressive absA1 mutant (C542) brought about
      pathway-specific restoration of actinorhodin and undecylprodigiosin production,
      respectively. Our results suggest that AbsA2 approximately P interacts with as
      many as four sites in the region that includes the actII-ORF4 promoter. These
      data suggest that AbsA2 approximately P inhibits antibiotic production by
      directly interfering with the expression of pathway-specific regulators of
      antibiotic biosynthetic gene clusters.

PMID- 17513474
TI  - Genetic interactions of DNA repair pathways in the pathogen Neisseria
      meningitidis.
AB  - The current increase in the incidence and severity of infectious diseases
      mandates improved understanding of the basic biology and DNA repair profiles of
      virulent microbes. In our studies of the major pathogen and model organism
      Neisseria meningitidis, we constructed a panel of mutants inactivating genes
      involved in base excision repair, mismatch repair, nucleotide excision repair
      (NER), translesion synthesis, and recombinational repair pathways. The highest
      spontaneous mutation frequency among the N. meningitidis single mutants was found
      in the MutY-deficient strain as opposed to mutS mutants in Escherichia coli,
      indicating a role for meningococcal MutY in antibiotic resistance development.
      Recombinational repair was recognized as a major pathway counteracting methyl
      methanesulfonate-induced alkylation damage in the N. meningitidis. In contrast to
      what has been shown in other species, meningococcal NER did not contribute
      significantly to repair of alkylation-induced DNA damage, and meningococcal
      recombinational repair may thus be one of the main pathways for removal of abasic
      (apurinic/apyrimidinic) sites and strand breaks in DNA. Conversely, NER was
      identified as the main meningococcal defense pathway against UV-induced DNA
      damage. N. meningitidis RecA single mutants exhibited only a moderate decrease in
      survival after UV exposure as opposed to E. coli recA strains, which are
      extremely UV sensitive, possibly reflecting the lack of a meningococcal SOS
      response. In conclusion, distinct differences between N. meningitidis and
      established DNA repair characteristics in E. coli and other species were
      identified.

PMID- 17513475
TI  - Identification of a novel streptococcal gene cassette mediating SOS mutagenesis
      in Streptococcus uberis.
AB  - Streptococci have been considered to lack the classical SOS response, defined by
      increased mutation after UV exposure and regulation by LexA. Here we report the
      identification of a potential self-regulated SOS mutagenesis gene cassette in the
      Streptococcaceae family. Exposure to UV light was found to increase mutations to
      antibiotic resistance in Streptococcus uberis cultures. The mutational spectra
      revealed mainly G:C-->A:T transitions, and Northern analyses demonstrated
      increased expression of a Y-family DNA polymerase resembling UmuC under DNA
      damaging conditions. In the absence of the Y-family polymerase, S. uberis cells
      were sensitive to UV light and to mitomycin C. Furthermore, the UV-induced
      mutagenesis was almost completely abolished in cells deficient in the Y-family
      polymerase. The gene encoding the Y-family polymerase was localized in a four
      gene operon including two hypothetical genes and a gene encoding a HdiR homolog.
      Electrophoretic mobility shift assays demonstrated that S. uberis HdiR binds
      specifically to an inverted repeat sequence in the promoter region of the four
      gene operon. Database searches revealed conservation of the gene cassette in
      several Streptococcus species, including at least one genome each of
      Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus mitis,
      Streptococcus sanguinis, and Streptococcus thermophilus strains. In addition, the
      umuC operon was localized in several mobile DNA elements of Streptococcus and
      Lactococcus species. We conclude that the hdiR-umuC-ORF3-ORF4 operon represents a
      novel gene cassette capable of mediating SOS mutagenesis among members of the
      Streptococcaceae.

PMID- 17513476
TI  - Transcription activation by the DNA-binding domain of the AraC family protein
      RhaS in the absence of its effector-binding domain.
AB  - The Escherichia coli L-rhamnose-responsive transcription activators RhaS and RhaR
      both consist of two domains, a C-terminal DNA-binding domain and an N-terminal
      dimerization domain. Both function as dimers and only activate transcription in
      the presence of L-rhamnose. Here, we examined the ability of the DNA-binding
      domains of RhaS (RhaS-CTD) and RhaR (RhaR-CTD) to bind to DNA and activate
      transcription. RhaS-CTD and RhaR-CTD were both shown by DNase I footprinting to
      be capable of binding specifically to the appropriate DNA sites. In vivo as well
      as in vitro transcription assays showed that RhaS-CTD could activate
      transcription to high levels, whereas RhaR-CTD was capable of only very low
      levels of transcription activation. As expected, RhaS-CTD did not require the
      presence of L-rhamnose to activate transcription. The upstream half-site at
      rhaBAD and the downstream half-site at rhaT were found to be the strongest of the
      known RhaS half-sites, and a new putative RhaS half-site with comparable strength
      to known sites was identified. Given that cyclic AMP receptor protein (CRP), the
      second activator required for full rhaBAD expression, cannot activate rhaBAD
      expression in a DeltarhaS strain, it was of interest to test whether CRP could
      activate transcription in combination with RhaS-CTD. We found that RhaS-CTD
      allowed significant activation by CRP, both in vivo and in vitro, although full
      length RhaS allowed somewhat greater CRP activation. We conclude that RhaS-CTD
      contains all of the determinants necessary for transcription activation by RhaS.

PMID- 17513477
TI  - What is the benefit to Escherichia coli of having multiple toxin-antitoxin
      systems in its genome?
AB  - The Escherichia coli K-12 chromosome encodes at least five proteic toxin
      antitoxin (TA) systems. The mazEF and relBE systems have been extensively
      characterized and were proposed to be general stress response modules. On one
      hand, mazEF was proposed to act as a programmed cell death system that is
      triggered by a variety of stresses. On the other hand, relBE and mazEF were
      proposed to serve as growth modulators that induce a dormancy state during amino
      acid starvation. These conflicting hypotheses led us to test a possible
      synergetic effect of the five characterized E. coli TA systems on stress
      response. We compared the behavior of a wild-type strain and its derivative
      devoid of the five TA systems under various stress conditions. We were unable to
      detect TA-dependent programmed cell death under any of these conditions, even
      under conditions previously reported to induce it. Thus, our results rule out the
      programmed-cell-death hypothesis. Moreover, the presence of the five TA systems
      advantaged neither recovery from the different stresses nor cell growth under
      nutrient-limited conditions in competition experiments. This casts a doubt on
      whether TA systems significantly influence bacterial fitness and competitiveness
      during non-steady-state growth conditions.

PMID- 17513478
TI  - Overproduction of penicillin-binding protein 2 and its inactive variants causes
      morphological changes and lysis in Escherichia coli.
AB  - Penicillin-binding protein 2 (PBP 2) has long been known to be essential for rod
      shaped morphology in gram-negative bacteria, including Escherichia coli and
      Pseudomonas aeruginosa. In the course of earlier studies with P. aeruginosa PBP
      2, we observed that E. coli was sensitive to the overexpression of its gene,
      pbpA. In this study, we examined E. coli overproducing both P. aeruginosa and E.
      coli PBP 2. Growth of cells entered a stationary phase soon after induction of
      gene expression, and cells began to lyse upon prolonged incubation. Concomitant
      with the growth retardation, cells were observed to have changed morphologically
      from typical rods into enlarged spheres. Inactive derivatives of the PBP 2s were
      engineered, involving site-specific replacement of their catalytic Ser residues
      with Ala in their transpeptidase module. Overproduction of these inactive PBPs
      resulted in identical effects. Likewise, overproduction of PBP 2 derivatives
      possessing only their N-terminal non-penicillin-binding module (i.e., lacking
      their C-terminal transpeptidase module) produced similar effects. However, E.
      coli overproducing engineered derivatives of PBP 2 lacking their noncleavable, N
      terminal signal sequence and membrane anchor were found to grow and divide at the
      same rate as control cells. The morphological effects and lysis were also
      eliminated entirely when overproduction of PBP 2 and variants was conducted with
      E. coli MHD79, a strain lacking six lytic transglycosylases. A possible
      interaction between the N-terminal domain of PBP 2 and lytic transglycosylases in
      vivo through the formation of multienzyme complexes is discussed.

PMID- 17513479
TI  - Requirement for YaeT in the outer membrane assembly of autotransporter proteins.
AB  - Autotransporters constitute the largest group of secreted proteins in gram
      negative bacteria. Autotransporter secretion involves the insertion of a carboxy
      terminal beta barrel into and the translocation of an amino-terminal domain
      across the outer membrane. Here, we demonstrate that secretion of
      autotransporters from several organisms requires the outer membrane assembly
      factor YaeT.

PMID- 17513480
TI  - Two genes encoding protein kinases of the HstK family are involved in synthesis
      of the minor heterocyst-specific glycolipid in the cyanobacterium Anabaena sp.
      strain PCC 7120.
AB  - The filamentous cyanobacterium Anabaena sp. strain PCC 7120 can fix N(2) under
      oxic conditions, and the activity of nitrogen fixation occurs exclusively in
      heterocysts, cells differentiated from vegetative cells in response to a
      limitation of a combined-nitrogen source in the growth medium. At the late stages
      of heterocyst differentiation, an envelope layer composed of two glycolipids is
      formed to limit the entry of oxygen so that the oxygen-sensitive nitrogenase can
      function. The genome of Anabaena sp. strain PCC 7120 possesses a family of 13
      genes (the hstK family), all encoding proteins with a putative Ser/Thr kinase
      domain at their N termini and a His-kinase domain at their C termini. In this
      study, we showed that the double mutant D4.3 strain, in which two members of this
      gene family, pkn44 (all1625) and pkn30 (all3691), were both inactivated, failed
      to fix N(2) in the presence of oxygen (Fox(-)). In an environment without oxygen,
      a low level of nitrogenase activity was detectable (Fix(+)). Heterocyst
      development in the mutant D4.3 was delayed by 24 h and arrested at a relatively
      early stage without the formation of the glycolipid layer (Hgl(-)). Only the
      minor species of the two heterocyst-specific glycolipids (HGLs) was missing in
      the mutant. We propose that DevH, a putative transcription factor, coordinates
      the synthesis of both HGLs, while Pkn44/Pkn30 and the previously characterized
      PrpJ may represent two distinct regulatory pathways involved in the synthesis of
      the minor HGL and the major HGL, respectively.

PMID- 17513481
TI  - Effects of iron deficiency on iron binding and internalization into acidic
      vacuoles in Dunaliella salina.
AB  - Uptake of iron in the halotolerant alga Dunaliella salina is mediated by a
      transferrin-like protein (TTf), which binds and internalizes Fe(3+) ions.
      Recently, we found that iron deficiency induces a large enhancement of iron
      binding, which is associated with accumulation of three other plasma membrane
      proteins that associate with TTf. In this study, we characterized the kinetic
      properties of iron binding and internalization and identified the site of iron
      internalization. Iron deficiency induces a 4-fold increase in Fe binding, but
      only 50% enhancement in the rate of iron uptake and also increases the affinity
      for iron and bicarbonate, a coligand for iron binding. These results indicate
      that iron deprivation leads to accumulation and modification of iron-binding
      sites. Iron uptake in iron-sufficient cells is preceded by an apparent time lag,
      resulting from prebound iron, which can be eliminated by unloading iron-binding
      sites. Iron is tightly bound to surface-exposed sites and hardly exchanges with
      medium iron. All bound iron is subsequently internalized. Accumulation of iron
      inhibits further iron binding and internalization. The vacuolar inhibitor
      bafilomycin inhibits iron uptake and internalization. Internalized iron was
      localized by electron microscopy within vacuolar structures that were identified
      as acidic vacuoles. Iron internalization is accompanied by endocytosis of surface
      proteins into these acidic vacuoles. A novel kinetic mechanism for iron uptake is
      proposed, which includes two pools of bound/compartmentalized iron separated by a
      rate-limiting internalization stage. The major parameter that is modulated by
      iron deficiency is the iron-binding capacity. We propose that excessive iron
      binding in iron-deficient cells serves as a temporary reservoir for iron that is
      subsequently internalized. This mechanism is particularly suitable for organisms
      that are exposed to large fluctuations in iron availability.

PMID- 17513482
TI  - Effects of the lack of phosphatidylglycerol on the donor side of photosystem II.
AB  - Our previous studies with the pgsA mutant of the cyanobacterium Synechocystis sp.
      PCC6803 (hereafter termed pgsA mutant), which is defective for the biosynthesis
      of phosphatidylglycerol (PG), revealed an important role for PG in the electron
      acceptor side of photosystem II (PSII), especially in the electron transport
      between plastoquinones Q(A) and Q(B). This study now shows that PG also plays an
      important role in the electron donor side of PSII, namely, the oxygen-evolving
      system. Analyses of purified PSII complexes indicated that PSII from PG-depleted
      pgsA mutant cells sustained only approximately 50% of the oxygen-evolving
      activity compared to wild-type cells. Dissociation of the extrinsic proteins
      PsbO, PsbV, and PsbU, which are required for stabilization of the manganese (Mn)
      cluster, followed by the release of a Mn atom, was observed in PSII of the PG
      depleted mutant cells. The released PsbO rebound to PSII when PG was added back
      to the PG-depleted mutant cells, even when de novo protein synthesis was
      inhibited. Changes in photosynthetic activity of the PG-depleted pgsA mutant
      cells induced by heat treatment or dark incubation resembled those of DeltapsbO,
      DeltapsbV, and DeltapsbU mutant cells. These results suggest that PG plays an
      important role in binding extrinsic proteins required for sustaining a functional
      Mn cluster on the donor side of PSII.

PMID- 17513483
TI  - Thioredoxin-linked proteins are reduced during germination of Medicago truncatula
      seeds.
AB  - Germination of cereals is accompanied by extensive change in the redox state of
      seed proteins. Proteins present in oxidized form in dry seeds are converted to
      the reduced state following imbibition. Thioredoxin (Trx) appears to play a role
      in this transition in cereals. It is not known, however, whether Trx-linked redox
      changes are restricted to cereals or whether they take place more broadly in
      germinating seeds. To gain information on this point, we have investigated a
      model legume, Medicago truncatula. Two complementary gel-based proteomic
      approaches were followed to identify Trx targets in seeds: Proteins were (1)
      labeled with a thiol-specific probe, monobromobimane (mBBr), following in vitro
      reduction by an NADP/Trx system, or (2) isolated on a mutant Trx affinity column.
      Altogether, 111 Trx-linked proteins were identified with few differences between
      axes and cotyledons. Fifty nine were new, 34 found previously in cereal or peanut
      seeds, and 18 in other plants or photosynthetic organisms. In parallel, the redox
      state of proteins assessed in germinating seeds using mBBr revealed that a
      substantial number of proteins that are oxidized or partly reduced in dry seeds
      became more reduced upon germination. The patterns were similar for proteins
      reduced in vivo during germination or in vitro by Trx. In contrast, glutathione
      and glutaredoxin were less effective as reductants in vitro. Overall, more than
      half of the potential targets identified with the mBBr labeling procedure were
      reduced during germination. The results provide evidence that Trx functions in
      the germination of seeds of dicotyledons as well as monocotyledons.

PMID- 17513484
TI  - Functional characterization of the Arabidopsis eukaryotic translation initiation
      factor 5A-2 that plays a crucial role in plant growth and development by
      regulating cell division, cell growth, and cell death.
AB  - The eukaryotic translation initiation factor 5A (eIF-5A) is a highly conserved
      protein found in all eukaryotic organisms. Although originally identified as a
      translation initiation factor, recent studies in mammalian and yeast
      (Saccharomyces cerevisiae) cells suggest that eIF-5A is mainly involved in RNA
      metabolism and trafficking, thereby regulating cell proliferation, cell growth,
      and programmed cell death. In higher plants, the physiological function of eIF-5A
      remains largely unknown. Here, we report the identification and characterization
      of an Arabidopsis (Arabidopsis thaliana) mutant fumonisin B(1)-resistant12
      (fbr12). The fbr12 mutant shows an antiapoptotic phenotype and has reduced dark
      induced leaf senescence. Moreover, fbr12 displays severe defects in plant growth
      and development. The fbr12 mutant plant is extreme dwarf with substantially
      reduced size and number of all adult organs. During reproductive development,
      fbr12 causes abnormal development of floral organs and defective sporogenesis,
      leading to the abortion of both female and male germline cells. Microscopic
      studies revealed that these developmental defects are associated with abnormal
      cell division and cell growth. Genetic and molecular analyses indicated that
      FBR12 encodes a putative eIF-5A-2 protein. When expressed in a yeast mutant
      strain carrying a mutation in the eIF-5A gene, FBR12 cDNA is able to rescue the
      lethal phenotype of the yeast mutant, indicating that FBR12 is a functional eIF
      5A. We propose that FBR12/eIF-5A-2 is fundamental for plant growth and
      development by regulating cell division, cell growth, and cell death.

PMID- 17513485
TI  - Expression of genomic AtCYCD2;1 in Arabidopsis induces cell division at smaller
      cell sizes: implications for the control of plant growth.
AB  - The Arabidopsis (Arabidopsis thaliana) CYCD2;1 gene introduced in genomic form
      increased cell formation in the Arabidopsis root apex and leaf, while generating
      full-length mRNA, raised CDK/CYCLIN enzyme activity, reduced G1-phase duration,
      and reduced size of cells at S phase and division. Other cell cycle genes,
      CDKA;1, CYCLIN B;1, and the cDNA form of CYCD2;1 that produced an aberrantly
      spliced mRNA, produced smaller or zero increases in CDK/CYCLIN activity and did
      not increase the number of cells formed. Plants with a homozygous single insert
      of genomic CYCD2;1 grew with normal morphology and without accelerated growth of
      root or shoot, not providing evidence that cell formation or CYCLIN D2 controls
      growth of postembryonic vegetative tissues. At the root apex, cells progressed
      normally from meristem to elongation, but their smaller size enclosed less growth
      and a 40% reduction in final size of epidermal and cortical cells was seen.
      Smaller elongated cell size inhibited endoreduplication, indicating a cell size
      requirement. Leaf cells were also smaller and more numerous during proliferation
      and epidermal pavement and palisade cells attained 59% and 69% of controls,
      whereas laminas reached normal size. Autonomous control of expansion was
      therefore not evident in abundant cell types that formed tissues of root or leaf.
      Cell size was reduced by a greater number formed in a tissue prior to cell and
      tissue expansion. Initiation and termination of expansion did not correlate with
      cell dimension or number and may be determined by tissue-wide signals acting
      across cellular boundaries.

PMID- 17513486
TI  - Are voltage-dependent ion channels involved in the endothelial cell control of
      vasomotor tone?
AB  - In the microcirculation, longitudinal conduction of vasomotor responses provides
      an essential means of coordinating flow distribution among vessels in a complex
      network. Spread of current along the vessel axis can display a regenerative
      component, which leads to propagation of vasomotor signals over many millimeters;
      the ionic basis for the regenerative response is unknown. We examined the
      responses to 10 s of focal electrical stimulation (30 Hz, 2 ms, 30 V) of mouse
      cremaster arterioles to test the hypothesis that voltage-dependent Na(+) (Na(v))
      and Ca(2+) channels might be activated in long-distance signaling in
      microvessels. Electrical stimulation evoked a vasoconstriction at the site of
      stimulation and a spreading, nondecremental conducted dilation. Endothelial
      damage (air bubble) blocked conduction of the vasodilation, indicating an
      involvement of the endothelium. The Na(v) channel blocker bupivacaine also
      blocked conduction, and TTX attenuated it. The Na(v) channel activator
      veratridine induced an endothelium-dependent dilation. The Na(v) channel isoforms
      Na(v)1.2, Na(v)1.6, and Na(v)1.9 were detected in the endothelial cells of
      cremaster arterioles by immunocytochemistry. These findings are consistent with
      the involvement of Na(v) channels in the conducted response. BAPTA buffering of
      endothelial cell Ca(2+) delayed and reduced the conducted dilation, which was
      almost eliminated by Ni(2+), amiloride, or deletion of alpha(1H) T-type Ca(2+)
      (Ca(v)3.2) channels. Blockade of endothelial nitric oxide synthase or Ca(2+)
      activated K(+) channels also inhibited the conducted vasodilation. Our findings
      indicate that an electrically induced signal can propagate along the vessel axis
      via the endothelium and can induce sequential activation of Na(v) and Ca(v)3.2
      channels. The resultant Ca(2+) influx activates endothelial nitric oxide synthase
      and Ca(2+)-activated K(+) channels, triggering vasodilation.

PMID- 17513487
TI  - In vitro and in vivo kinetic handling of nitrite in blood: effects of varying
      hemoglobin oxygen saturation.
AB  - Growing evidence suggests that nitrite, acting via reduction to nitric oxide by
      deoxyhemoglobin, may play an important role in local control of blood flow during
      hypoxia. To investigate the effect of hypoxia (65 Torr arterial Po(2)) on the
      kinetic properties of nitrite, a bolus injection of sodium nitrite (10 mg/kg iv)
      was given to normoxic or hypoxic newborn lambs, and the time course of plasma
      nitrite and methemoglobin (MetHb) concentrations was measured. The in vivo
      kinetics of nitrite disappearance from plasma were biphasic and were not affected
      by hypoxia. Changes in MetHb, a product of the nitrite-hemoglobin reaction, also
      did not differ with the level of oxygenation. Hypoxia potentiated the hypotensive
      effects of nitrite on pulmonary and systemic arterial pressures. The
      disappearance of nitrite from plasma was equivalent to the increase in MetHb on a
      molar basis. In contrast, nitrite metabolism in sheep blood in vitro resulted in
      more than one MetHb per nitrite equivalent under mid- and high-oxygenation
      conditions: oxyhemoglobin (HbO(2)) saturation = 50.3 +/- 1.7% and 97.0 +/- 1.3%,
      respectively. Under the low-oxygenation condition (HbO(2) saturation = 5.2 +/-
      0.9%), significantly less than 1 mol of MetHb was produced per nitrite
      equivalent, indicating that a significant portion of nitrite is metabolized
      through pathways that do not produce MetHb. These data support the idea that the
      vasodilating effects of nitrite are potentiated under hypoxic conditions due to
      the reduction of nitrite to nitric oxide by deoxyhemoglobin.

PMID- 17513488
TI  - Age-related changes in lamin A/C expression in cardiomyocytes.
AB  - Lamin A and C (A/C) are type V intermediate filaments that form the nuclear
      lamina. Lamin A/C mutations lead to reduced expression of lamin A/C and diverse
      phenotypes such as familial cardiomyopathies and accelerated aging syndromes.
      Normal aging is associated with reduced expression of lamin A/C in osteoblasts
      and dermal fibroblasts but has never been assessed in cardiomyocytes. Our
      objective was to compare the expression of lamin A/C in cardiomyocytes of old (24
      mo) versus young (4 mo) C57Bl/6J mice using a well-validated mouse model of
      aging. Lamin B1 was used as a control. Immunohistochemical and immunofluorescence
      analyses showed reduced expression of lamin A/C in cardiomyocyte nuclei of old
      mice (proportion of nuclei expressing lamin A/C, 9% vs. 62%, P < 0.001). Lamin
      A/C distribution was scattered peripherally and perinuclear in old mice, whereas
      it was homogeneous throughout the nuclei in young mice. Western blot analyses
      confirmed reduced expression of lamin A/C in nuclear extracts of old mice (ratio
      of lamin A/C to B1, 0.6 vs. 1.2, P < 0.01). Echocardiographic studies showed
      increased left ventricular wall thickness with preserved cavity size (concentric
      remodeling), increased left ventricular mass, and a slight reduction in
      fractional shortening in old mice. This is the first study to show that normal
      aging is associated with reduced expression and altered distribution of lamin A/C
      in nuclei of cardiomyocytes.

PMID- 17513489
TI  - High oxygen tension constricts epineurial arterioles of the rat sciatic nerve via
      reactive oxygen species.
AB  - Microcirculation of the sheath of the rat sciatic nerve fiber was investigated by
      using an intravital microscope, and changes in the diameter of the epineurial
      arterioles in response to highly oxygenated Krebs-bicarbonate solution were
      evaluated. Superfusion of low-oxygen (0%) Krebs-bicarbonate solution (LKS) onto
      rat sciatic nerves did not affect changes in the diameter of the arterioles.
      Nifedipine, a Ca(2+)-channel blocker, caused a dose-dependent dilation of the
      epineurial arterioles in LKS. In contrast, superfusion of high-oxygen (21%) Krebs
      bicarbonate solution (HKS) onto rat sciatic nerves significantly constricted the
      epineurial arterioles in a time-dependent manner. The HKS-induced constriction of
      the epineurial arterioles was significantly reduced by treatment with 120 U/ml
      superoxide dismutase (SOD) alone or 5,000 U/ml catalase alone. In the presence of
      120 U/ml SOD plus 5,000 U/ml catalase, 10(-4) M tempol, 10(-6) M
      diphenyleneiodium, 2 x 10(-4) M apocynin, or 10(-6) M allopurinol, the HKS
      induced constriction of the epineurial arterioles completely disappeared. These
      results suggest that superfusion of highly oxygenated solution onto rat sciatic
      nerves constricts the epineurial arterioles through reactive oxygen species
      (ROS), including superoxide and hydrogen peroxide, and that production of
      superoxide involves a NADPH oxidase- or xanthine oxidase-dependent pathway. In
      conclusion, ROS play significant roles in the regulation of microcirculation of
      rat sciatic nerves in vivo.

PMID- 17513490
TI  - Delta-opioid receptor activation before ischemia reduces gap junction
      permeability in ischemic myocardium by PKC-epsilon-mediated phosphorylation of
      connexin 43.
AB  - The aim of this study was to examine the hypothesis that delta-opioid receptor
      activation before ischemia suppresses gap junction (GJ) permeability by PKC
      mediated connexin 43 (Cx43) modulation, which contributes to infarct size
      limitation afforded by the delta-opioid receptor activation. A delta-opioid
      receptor agonist, [D-Ala(2),D-Leu(5)]-enkephalin acetate (DADLE, 300 nM), was
      used in place of preconditioning (PC) ischemia to trigger PC mechanisms in rat
      hearts. GJ permeability during ischemia, which was assessed by Lucifer yellow,
      was reduced by DADLE to 47% of the control level, and this effect of DADLE was
      almost abolished by a PKC-epsilon inhibitor [PKC-epsilon translocation inhibitory
      peptide (PKC-epsilon-TIP)] but was not affected by a PKC-delta inhibitor
      (rottlerin). After DADLE infusion, PKC-epsilon, but not PKC-delta, was
      coimmunoprecipitated with Cx43, and the level of phosphorylation of Cx43 at a PKC
      dependent site (Ser(368)) was significantly elevated during ischemia. DADLE
      reduced infarct size after 35 min of ischemia followed by 2 h of reperfusion by
      69%, and PKC-epsilon-TIP and rottlerin eliminated 48% and 63%, respectively, of
      the infarct size-limiting effect of DADLE. Infusion of a GJ blocker, heptanol,
      before reperfusion reduced infarct size by 36%, and this protection was not
      enhanced by preischemic infusion of rottlerin + DADLE, which allows PKC-epsilon
      activation by DADLE. These results suggest that phosphorylation of Cx43 by PKC
      epsilon plays a crucial role in delta-opioid-induced suppression of GJ
      permeability in ischemic myocardium and that this modulation of the GJ is
      possibly an adjunct mechanism of infarct size limitation afforded by preischemic
      delta-opioid receptor activation.

PMID- 17513492
TI  - The mitochondrial permeability transition pore as a target of cardioprotective
      signaling.

PMID- 17513491
TI  - Regulation of collagen synthesis by inhibitory Smad7 in cardiac myofibroblasts.
AB  - Transforming growth factor-beta(1) (TGF-beta(1)) signal and downstream Smads play
      an important role in tissue fibrosis and matrix remodeling in various etiologies
      of heart failure. Inhibitory Smad7 (I-Smad7) is an inducible regulatory Smad
      protein that antagonizes TGF-beta(1) signal mediated via direct abrogation of R
      Smad phosphorylation. The effect of ectopic I-Smad7 on net collagen production
      was investigated using hydroxyproline assay. Adenovirus-mediated I-Smad7 gene (at
      100 multiplicity of infection) transfer was associated with significant decrease
      of collagen synthesis in the presence and absence of TGF-beta(1) in primary rat
      cardiac myofibroblasts. In I-Smad7-infected cells, we also observed the ablation
      of TGF-beta(1)-induced R-Smad2 phosphorylation vs. LacZ controls. Overdriven I
      Smad7 was associated with significantly increased expression of immunoreactive 65
      kDa matrix metalloproteinase-2 (MMP-2) protein in culture medium of myofibroblast
      compared with LacZ-infected cells. Expression of the 72-kDa MMP-2 variant, e.g.,
      the inactive form, was not altered by exogenous I-Smad7
      transfection/overexpression. Furthermore, I-Smad7 overexpression was associated
      with a significant increase and decrease in expression of p27 and phospho-Rb
      protein, respectively, as well as reduced [(3)H]thymidine incorporation vs. Ad
      LacZ-infected controls. We suggest that negative modulation of R-Smad
      phosphorylation by ectopic I-Smad7 may contribute to the downregulation of
      collagen in cardiac myofibroblasts and may suppress the proliferation of these
      cells. Thus treatments targeting the collagen deposition by overexpression of I
      Smad7 may provide a new therapeutic strategy for cardiac fibrosis.

PMID- 17513493
TI  - A method to collect isolated myocytes and whole tissue from the same heart.
AB  - A technique for isolation of cardiac myocytes and collection of whole heart
      tissue from individual hearts of adult rats is described in this study. After
      excision of the apical half of the left ventricle (LV) and cauterization of the
      cut edge, aortas were cannulated and high-quality isolated cardiac myocytes were
      collected after collagenase perfusion of the basal portion. Myocyte dimensions
      from the basal portion of cauterized and noncauterized hearts from matching rats
      were identical. Additionally, myocyte dimensions from the basal and apical halves
      of the LV were compared with the use of whole heart-isolated myocyte preps. No
      regional differences between basal and apical LV myocyte size were found.
      Therefore, this cauterization method can be used to collect isolated myocytes
      from the basal half and whole heart tissue from the apical half, with each half
      being representative of the other with respect to myocyte dimensions.

PMID- 17513494
TI  - H2O2 activation of HSP25/27 protects desmin from calpain proteolysis in rat
      ventricular myocytes.
AB  - Ischemia-reperfusion-induced Ca(2+) overload results in activation of calpain-1
      in the heart. Calpain-dependent proteolysis contributes to myocardial dysfunction
      and cell death. Previously, preischemic treatment with low doses of H(2)O(2) was
      shown to improve postischemic function and reduce myocardial infarct size. Our
      aim was to determine the mechanism by which H(2)O(2) protects the heart. We
      hypothesized that H(2)O(2) causes the activation of p38 MAPK which initiates
      translocation of heat shock protein 25/27 (HSP25/27) to the myofilament Z disk.
      We further hypothesized that HSP25/27 shields structural proteins, particularly
      desmin, from calpain-induced proteolysis. To address this hypothesis, we first
      determined that an ischemia-reperfusion-induced decrease in desmin content could
      be blocked by H(2)O(2) pretreatment of hearts from rats. We next determined that
      ventricular myocytes that underwent Ca(2+) overload also demonstrated a calpain
      dependent disruption of desmin that could be reduced by H(2)O(2)/p38 MAPK
      activation. Furthermore, myocytes acutely treated with H(2)O(2) exhibited a
      decrease in cleavage of desmin upon exposure to exogenous calpain-1 compared with
      myocytes not pretreated with H(2)O(2). The H(2)O(2)-induced attenuation of desmin
      degradation by calpain-1 was blocked by inhibition of p38 MAPK. In a final series
      of experiments, we demonstrated that cardiac myofilaments exposed to recombinant
      phosphorylated HSP27, but not nonphosphorylated HSP27, had a significant
      reduction in the calpain-induced degradation of desmin compared with non-HSP27
      treated myofilaments. These findings are consistent with the hypothesis that
      H(2)O(2)-induced activation of p38 MAPK and subsequent HSP25/27 translocation
      attenuates desmin degradation brought about by calpain-1 activation in ischemia
      reperfused hearts.

PMID- 17513496
TI  - Imbalance between endothelium-derived relaxing and contracting factors in
      mesenteric arteries from aged OLETF rats, a model of Type 2 diabetes.
AB  - We investigated whether the balance between endothelium-derived relaxing factors
      (EDRFs) and endothelium-derived contracting factors (EDCFs) might be altered in
      mesenteric arteries from aged Otsuka Long-Evans Tokushima Fatty (OLETF) rats (a
      Type 2 diabetic model) [vs. age-matched control Long-Evans Tokushima Otsuka
      (LETO) rats]. ACh-induced relaxation was impaired in the OLETF group, and a
      tendency for the relaxation to reverse at high ACh concentrations was observed in
      both groups. This tendency was abolished by indomethacin. Nitric oxide- and/or
      endothelium-derived hypolarizing factor-mediated relaxation and the protein
      expressions of phospho-endothelial nitric oxide synthase (Ser1177) and
      extracellular superoxide dismutase were also reduced in OLETF. An ACh-induced
      contraction was observed at higher ACh concentrations in the presence of N(G)
      nitro-L-arginine (L-NNA) but was greater in OLETF rats. This contraction in OLETF
      rats was reduced by cyclooxygenase (COX) inhibitors and by prostanoid-receptor
      antagonists. The ACh-induced productions of thromboxane A(2) and PGE(2) were
      greater in OLETF than LETO rats, as were the mesenteric artery COX-1 and COX-2
      protein expressions. Moreover, tert-butyl hydroperoxide (t-BOOH) (membrane
      permeant oxidant) induced a concentration-dependent contraction that was greater
      in OLETF rats. The t-BOOH-mediated contraction was increased both by L-NNA and by
      endothelium removal in LETO but not OLETF rats, suggesting that a negative
      modulatory role of the endothelium was lost in OLETF rats. These results suggest
      that an imbalance between EDRFs and EDCFs may be implicated in the endothelial
      dysfunction seen in aged OLETF mesenteric arteries, and may be attributable to
      increased oxidative stress.

PMID- 17513495
TI  - Ischemic preconditioning prevents in vivo hyperoxygenation in postischemic
      myocardium with preservation of mitochondrial oxygen consumption.
AB  - Ischemic preconditioning (IPC) strongly protects against ischemia-reperfusion
      injury; however, its effect on subsequent myocardial oxygenation is unknown.
      Therefore, we determine in an in vivo mouse model of regional ischemia and
      reperfusion (I/R) if IPC attenuates postischemic myocardial hyperoxygenation and
      decreases formation of reactive oxygen/nitrogen species (ROS/RNS), with
      preservation of mitochondrial function. The following five groups of mice were
      studied: sham, control (I/R), ischemic preconditioning (IPC + I/R, 3 cycles of 5
      min coronary occlusion/5 min reperfusion) and IPC + I/R N(G)-nitro-L-arginine
      methyl ester treated, and IPC + I/R eNOS knockout mice. I/R and IPC + I/R mice
      were subjected to 30 min regional ischemia followed by 60 min reperfusion.
      Myocardial Po(2) and redox state were monitored by electron paramagnetic
      resonance spectroscopy. In the IPC + I/R, but not the I/R group, regional blood
      flow was increased after reperfusion. Po(2) upon reperfusion increased
      significantly above preischemic values in I/R but not in IPC + I/R mice. Tissue
      redox state was measured from the reduction rate of a spin probe, and this rate
      was 60% higher in IPC than in non-IPC hearts. Activities of NADH dehydrogenase
      (NADH-DH) and cytochrome c oxidase (CcO) were reduced in I/R mice after 60 min
      reperfusion but conserved in IPC + I/R mice compared with sham. There were no
      differences in NADH-DH and CcO expression in I/R and IPC + I/R groups compared
      with sham. After 60 min reperfusion, strong nitrotyrosine formation was observed
      in I/R mice, but only weak staining was observed in IPC + I/R mice. Thus IPC
      markedly attenuates postischemic myocardial hyperoxygenation with less ROS/RNS
      generation and preservation of mitochondrial O(2) metabolism because of conserved
      NADH-DH and CcO activities.

PMID- 17513497
TI  - Reverse electron flow-induced ROS production is attenuated by activation of
      mitochondrial Ca2+-sensitive K+ channels.
AB  - Mitochondria generate reactive oxygen species (ROS) dependent on substrate
      conditions, O(2) concentration, redox state, and activity of the mitochondrial
      complexes. It is well known that the FADH(2)-linked substrate succinate induces
      reverse electron flow to complex I of the electron transport chain and that this
      process generates superoxide (O(2)(*-)); these effects are blocked by the complex
      I blocker rotenone. We demonstrated recently that succinate + rotenone-dependent
      H(2)O(2) production in isolated mitochondria increased mildly on activation of
      the putative big mitochondrial Ca(2+)-sensitive K(+) channel (mtBK(Ca)) by low
      concentrations of 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5
      (trifluoromethyl)-2H-benzimidazol-2-one (NS-1619). In the present study we
      examined effects of NS-1619 on mitochondrial O(2) consumption, membrane potential
      (DeltaPsi(m)), H(2)O(2) release rates, and redox state in isolated guinea pig
      heart mitochondria respiring on succinate but without rotenone. NS-1619 (30
      microM) increased state 2 and state 4 respiration by 26 +/- 4% and 14 +/- 4%,
      respectively; this increase was abolished by the BK(Ca) channel blocker paxilline
      (5 microM). Paxilline alone had no effect on respiration. NS-1619 did not alter
      DeltaPsi(m) or redox state but decreased H(2)O(2) production by 73% vs. control;
      this effect was incompletely inhibited by paxilline. We conclude that under
      substrate conditions that allow reverse electron flow, matrix K(+) influx through
      mtBK(Ca) channels reduces mitochondrial H(2)O(2) production by accelerating
      forward electron flow. Our prior study showed that NS-1619 induced an increase in
      H(2)O(2) production with blocked reverse electron flow. The present results
      suggest that NS-1619-induced matrix K(+) influx increases forward electron flow
      despite the high reverse electron flow, and emphasize the importance of substrate
      conditions on interpretation of effects on mitochondrial bioenergetics.

PMID- 17513498
TI  - The role of nitric oxide synthase-derived reactive oxygen species in the altered
      relaxation of pulmonary arteries from lambs with increased pulmonary blood flow.
AB  - Congenital cardiac defects associated with increased pulmonary blood flow (Q(p))
      produce pulmonary hypertension. We have previously reported attenuated
      endothelium-dependent relaxations in pulmonary arteries (PA) isolated from lambs
      with increased Q(p) and pulmonary hypertension. To better characterize the
      vascular alterations in the nitric oxide-superoxide system, 12 fetal lambs
      underwent in utero placement of an aortopulmonary vascular graft (shunt). Twin
      lambs served as controls. PA were isolated from these lambs at 4-6 wk of age.
      Electron paramagnetic resonance spectroscopy on fourth-generation PA showed
      significantly increased superoxide anion generation in shunt PA that were
      decreased to control levels following inhibition of nitric oxide synthase (NOS)
      with 2-ethyl-2-thiopseudourea. Preconstricted fifth-generation PA rings were
      relaxed with a NOS agonist (A-23187), a nitric oxide donor [S-nitrosyl amino
      penicillamine (SNAP)], polyethylene glycol-conjugated superoxide dismutase (PEG
      SOD), or H(2)O(2). A-23187-, PEG-SOD-, and H(2)O(2)-mediated relaxations were
      impaired in shunt PA compared with controls. Pretreatment with PEG-SOD
      significantly enhanced the relaxation response to A-23187 and SNAP in shunt but
      not control PA. Inhibition of NOS with nitro-L-arginine or scavenging superoxide
      anions with tiron enhanced relaxation to SNAP and inhibited relaxation to PEG-SOD
      in shunt PA. Pretreatment with catalase inhibited relaxation of shunt PA to A
      23187, SOD, and H(2)O(2). We conclude that NOS catalyzes the production of
      superoxide anions in shunt PA. PEG-SOD relaxes shunt PA by converting these
      anions to H(2)O(2), a pulmonary vasodilator. The redox environment, influenced by
      the balance between production and scavenging of ROS, may have important
      consequences on pulmonary vascular reactivity in the setting of increased Q(p).

PMID- 17513499
TI  - NUCLEAR PORE ANCHOR, the Arabidopsis homolog of Tpr/Mlp1/Mlp2/megator, is
      involved in mRNA export and SUMO homeostasis and affects diverse aspects of plant
      development.
AB  - Vertebrate Tpr and its yeast homologs Mlp1/Mlp2, long coiled-coil proteins of
      nuclear pore inner basket filaments, are involved in mRNA export, telomere
      organization, spindle pole assembly, and unspliced RNA retention. We identified
      Arabidopsis thaliana NUCLEAR PORE ANCHOR (NUA) encoding a 237-kD protein with
      similarity to Tpr. NUA is located at the inner surface of the nuclear envelope in
      interphase and in the vicinity of the spindle in prometaphase. Four T-DNA
      insertion lines were characterized, which comprise an allelic series of
      increasing severity for several correlating phenotypes, such as early flowering
      under short days and long days, increased abundance of SUMO conjugates, altered
      expression of several flowering regulators, and nuclear accumulation of poly(A)+
      RNA. nua mutants phenocopy mutants of EARLY IN SHORT DAYS4 (ESD4), an Arabidopsis
      SUMO protease concentrated at the nuclear periphery. nua esd4 double mutants
      resemble nua and esd4 single mutants, suggesting that the two proteins act in the
      same pathway or complex, supported by yeast two-hybrid interaction. Our data
      indicate that NUA is a component of nuclear pore-associated steps of sumoylation
      and mRNA export in plants and that defects in these processes affect the
      signaling events of flowering time regulation and additional developmental
      processes.

PMID- 17513500
TI  - Canonical signal recognition particle components can be bypassed for
      posttranslational protein targeting in chloroplasts.
AB  - The chloroplast signal recognition particle (cpSRP) and its receptor (cpFtsY)
      target proteins both cotranslationally and posttranslationally to the thylakoids.
      This dual function enables cpSRP to utilize its posttranslational activities for
      targeting a family of nucleus-encoded light-harvesting chlorophyll binding
      proteins (LHCPs), the most abundant membrane proteins in plants. Previous in
      vitro experiments indicated an absolute requirement for all cpSRP pathway soluble
      components. In agreement, a cpFtsY mutant in Arabidopsis thaliana exhibits a
      severe chlorotic phenotype resulting from a massive loss of LHCPs. Surprisingly,
      a double mutant, cpftsy cpsrp54, recovers to a great extent from the chlorotic
      cpftsy phenotype. This establishes that in plants, a new alternative pathway
      exists that can bypass cpSRP posttranslational targeting activities. Using a
      mutant form of cpSRP43 that is unable to assemble with cpSRP54, we complemented
      the cpSRP43-deficient mutant and found that this subunit is required for the
      alternative pathway. Along with the ability of cpSRP43 alone to bind the ALBINO3
      translocase required for LHCP integration, our results indicate that cpSRP43 has
      developed features to function independently of cpSRP54/cpFtsY in targeting LHCPs
      to the thylakoid membranes.

PMID- 17513501
TI  - ABA is an essential signal for plant resistance to pathogens affecting JA
      biosynthesis and the activation of defenses in Arabidopsis.
AB  - Analyses of Arabidopsis thaliana defense response to the damping-off oomycete
      pathogen Pythium irregulare show that resistance to P. irregulare requires a
      multicomponent defense strategy. Penetration represents a first layer, as
      indicated by the susceptibility of pen2 mutants, followed by recognition, likely
      mediated by ERECTA receptor-like kinases. Subsequent signaling of inducible
      defenses is predominantly mediated by jasmonic acid (JA), with insensitive coi1
      mutants showing extreme susceptibility. In contrast with the generally accepted
      roles of ethylene and salicylic acid cooperating with or antagonizing,
      respectively, JA in the activation of defenses against necrotrophs, both are
      required to prevent disease progression, although much less so than JA. Meta
      analysis of transcriptome profiles confirmed the predominant role of JA in
      activation of P. irregulare-induced defenses and uncovered abscisic acid (ABA) as
      an important regulator of defense gene expression. Analysis of cis-regulatory
      sequences also revealed an unexpected overrepresentation of ABA response elements
      in promoters of P. irregulare-responsive genes. Subsequent infections of ABA
      related and callose-deficient mutants confirmed the importance of ABA in defense,
      acting partly through an undescribed mechanism. The results support a model for
      ABA affecting JA biosynthesis in the activation of defenses against this
      oomycete.

PMID- 17513502
TI  - Tomato BRASSINOSTEROID INSENSITIVE1 is required for systemin-induced root
      elongation in Solanum pimpinellifolium but is not essential for wound signaling.
AB  - The tomato Leu-rich repeat receptor kinase BRASSINOSTEROID INSENSITIVE1 (BRI1)
      has been implicated in both peptide (systemin) and steroid (brassinosteroid [BR])
      hormone perception. In an attempt to dissect these signaling pathways, we show
      that transgenic expression of BRI1 can restore the dwarf phenotype of the tomato
      curl3 (cu3) mutation. Confirmation that BRI1 is involved in BR signaling is
      highlighted by the lack of BR binding to microsomal fractions made from cu3
      mutants and the restoration of BR responsiveness following transformation with
      BRI1. In addition, wound and systemin responses in the cu3 mutants are
      functional, as assayed by proteinase inhibitor gene induction and rapid
      alkalinization of culture medium. However, we observed BRI1-dependent root
      elongation in response to systemin in Solanum pimpinellifolium. In addition,
      ethylene perception is required for normal systemin responses in roots. These
      data taken together suggest that cu3 is not defective in systemin-induced wound
      signaling and that systemin perception can occur via a non-BRI1 mechanism.

PMID- 17513503
TI  - Components of the Arabidopsis mRNA decapping complex are required for early
      seedling development.
AB  - To understand the mechanisms controlling vein patterning in Arabidopsis thaliana,
      we analyzed two phenotypically similar mutants, varicose (vcs) and trident (tdt).
      We had previously identified VCS, and recently, human VCS was shown to function
      in mRNA decapping. Here, we report that TDT encodes the mRNA-decapping enzyme.
      VCS and TDT function together in small cytoplasmic foci that appear to be
      processing bodies. To understand the developmental requirements for mRNA
      decapping, we characterized the vcs and tdt phenotypes. These mutants were small
      and chlorotic, with severe defects in shoot apical meristem formation and
      cotyledon vein patterning. Many capped mRNAs accumulated in tdt and vcs mutants,
      but surprisingly, some mRNAs were specifically depleted. In addition, loss of
      decapping arrested the decay of some mRNAs, while others showed either modest or
      no decay defects, suggesting that mRNAs may show specificity for particular decay
      pathways (3' to 5' and 5' to 3'). Furthermore, the severe block to postembryonic
      development in vcs and tdt and the accompanying accumulation of embryonic mRNAs
      indicate that decapping is important for the embryo-to-seedling developmental
      transition.

PMID- 17513505
TI  - Storiform collagenoma as a clue for Cowden disease or PTEN hamartoma tumour
      syndrome.

PMID- 17513504
TI  - The senescence-induced staygreen protein regulates chlorophyll degradation.
AB  - Loss of green color in leaves results from chlorophyll (Chl) degradation in
      chloroplasts, but little is known about how Chl catabolism is regulated
      throughout leaf development. Using the staygreen (sgr) mutant in rice (Oryza
      sativa), which maintains greenness during leaf senescence, we identified Sgr, a
      senescence-associated gene encoding a novel chloroplast protein. Transgenic rice
      overexpressing Sgr produces yellowish-brown leaves, and Arabidopsis thaliana
      pheophorbide a oxygenase-impaired mutants exhibiting a stay-green phenotype
      during dark-induced senescence have reduced expression of Sgr homologs,
      indicating that Sgr regulates Chl degradation at the transcriptional level. We
      show that the leaf stay-greenness of the sgr mutant is associated with a failure
      in the destabilization of the light-harvesting chlorophyll binding protein (LHCP)
      complexes of the thylakoid membranes, which is a prerequisite event for the
      degradation of Chls and LHCPs during senescence. Transient overexpression of Sgr
      in Nicotiana benthamiana and an in vivo pull-down assay show that Sgr interacts
      with LHCPII, indicating that the Sgr-LHCPII complexes are formed in the thylakoid
      membranes. Thus, we propose that in senescing leaves, Sgr regulates Chl
      degradation by inducing LHCPII disassembly through direct interaction, leading to
      the degradation of Chls and Chl-free LHCPII by catabolic enzymes and proteases,
      respectively.

PMID- 17513506
TI  - Fatal case of sepsis caused by a non-haemolytic strain of Streptococcus pyogenes.

PMID- 17513507
TI  - Molecular pathology of familial gastric cancer, with an emphasis on hereditary
      diffuse gastric cancer.
AB  - Gastric cancer is one of the major causes of cancer-related death worldwide.
      Familial clustering is observed in about 10% of cases; 1-3% of cases are
      hereditary. In the latter group, a syndrome which has been well characterised is
      hereditary diffuse gastric cancer; this is specifically associated with CDH1 (E
      cadherin) germline mutations in about 30% of families. In this article, the state
      of the art of familial gastric cancer regarding the clinical, molecular and
      pathology features is reviewed, as well as the practical aspects for a correct
      diagnosis and clinical management.

PMID- 17513508
TI  - Dysembryoplastic neuroepithelial tumours: clinical, proliferative and apoptotic
      features.
AB  - AIMS: Dysembryoplastic neuroepithelial tumours (DNTs) have been considered benign
      lesions characterised by a chronic, indolent clinical course. Previous studies
      have suggested that increased proliferation rates may be balanced by
      corresponding rates of apoptosis. The objective of this study was to determine
      whether a correlation exists between histological features and indices of
      proliferation/apoptosis. METHODS: Fourteen consecutive surgical specimens meeting
      the histological criteria for DNT were retrospectively reviewed for evidence of
      aggressive histological features, including anaplasia, mitotic activity, and Ki67
      labelling. Immunohistochemistry was performed semiquantitatively to evaluate and
      compare proliferation (Ki76) and apoptosis (TUNEL). The clinical course of the
      patients was also reviewed. RESULTS: Atypical histological features were
      demonstrated in the glial component of select complex DNTs. TUNEL indices,
      however, had negligible correlation with proliferative indices. A balance between
      cell proliferation and apoptosis was not evident particularly in those cases
      displaying aggressive histological features. CONCLUSIONS: While there is no
      clearly defined clinical or pathological pattern to indicate aggressive growth of
      DNTs, elevated proliferative indices coupled with atypical histological features
      in complex DNTs should be taken into consideration in determining the
      aggressiveness of surgical extirpation and follow-up until experience with these
      uncommon tumours is greater.

PMID- 17513509
TI  - Urinary bladder xanthoma: a report of 2 rare cases highlighted with anti-CD68
      antibody.

PMID- 17513510
TI  - Low-grade abdominopelvic sarcoma with myofibroblastic features (low-grade
      myofibroblastic sarcoma): clinicopathological, immunohistochemical, molecular
      genetic and ultrastructural study of two cases with literature review.
AB  - AIMS: Low-grade myofibroblastic sarcoma (LGMS) represents a rare soft tissue
      neoplasm with a predilection for the head and neck. Intra-abdominal LGMS are rare
      with only four unequivocal examples reported so far. Two further cases in females
      in their 60s and 70s are analysed here. METHODS: Immunohistochemical stains were
      applied on fresh-cut sections using the avidin-biotin complex method and the
      following antibodies: vimentin, alpha-SMA, desmin, h-caldesmon, S-100, CD117,
      CD34, fibronectin, HMB45, Pan-keratin, Ki-67, beta-catenin, MDM2, PDGFRalpha,
      PDGFRbeta and ALK-1. Genomic DNA was isolated from microdissected formalin-fixed
      paraffin-embedded tumour tissue and examined for KIT and PDGFRA mutations by PCR
      and direct sequencing of KIT and PDGFRA. Ultrastructural studies were also
      performed. RESULTS: The tumours arose in the mesentery and the pelvic peritoneum.
      Both revealed features intermediate between conventional fibrosarcoma and
      leiomyosarcoma with fascicles of spindled, stellated or plump cells possessing
      fusiform indented vesicular nuclei and pale eosinophilic cytoplasm. Mitotic
      activity ranged from 1 to 15 per 10 HPFs. The tumour cells strongly expressed
      vimentin, variably alpha-smooth muscle actin and fibronectin, but were negative
      for CD117, S-100, desmin, h-caldesmon, beta-catenin, ALK-1, MDM2, PDGFRalpha and
      PDGFRbeta. One tumour showed a weak expression of CD34. Molecular analysis
      revealed a wild-type KIT, exons 9, 11 and 13, and PDGFRA, exons 12 and 18. The
      patients developed multiple peritoneal recurrences at 5, 13 and 25 months, and
      10, 19, 25 and 32 months, and were alive at 25 and 32 months, respectively.
      Distant metastases were not detected. CONCLUSION: Abdominopelvic LGMS follows a
      more aggressive clinical course characterised by a higher propensity for local
      recurrence, contrasting their more superficially located counterparts. LGMS may
      mimic a variety of benign and low-grade malignant neoplasms and might be under
      recognised.

PMID- 17513511
TI  - BNIP3 expression in endometrial cancer relates to active hypoxia inducible factor
      1alpha pathway and prognosis.
AB  - AIMS: BNIP3 is a pro-apoptotic mitochondrial protein induced under hypoxic
      stress, with the BNIP3 gene being under direct regulation of the hypoxia
      inducible HIF-1alpha transcription factor. Induction of BNIP3 leads to caspase
      independent necrosis-like cell death and an aggressive tumour phenotype. The role
      of BNIP3 in endometrial cancer was examined. METHODS: The immunohistochemical
      patterns of BNIP3 expression in 72 early endometrial adenocarcinomas of the
      endometrioid cell type were studied. Correlation of BNIP3 with the hypoxia
      inducible factor HIF-1alpha pathway and with prognosis was also examined.
      RESULTS: BNIP3 was strongly and extensively expressed in the cytoplasm of cancer
      cells in 23/72 (31.9%) cases. This high BNIP3 reactivity was not related to
      histological grade, depth of myometrial invasion or steroid hormone receptor
      expression. There was, however, a significant association of BNIP3 reactivity
      with HIF-1alpha (p = 0.04), VEGF (p = 0.04) and, particularly, LDH-5 expression
      (p = 0.0001). Furthermore, high BNIP3 was associated with poor survival in both
      univariate (p = 0.05) and multivariate (p = 0.03) models. CONCLUSION: BNIP3 seems
      to be an important hypoxia-regulated molecule involved in endometrial cancer
      pathology. Given that high BNIP3 reactivity, being linked with poor post
      operative outcome, has been linked with a favourable response to cytotoxic
      therapy (as previously indicated in experimental studies), high BNIP3 expression
      may be an indicator for adjuvant chemoradiotherapy in stage I endometrial
      carcinomas.

PMID- 17513512
TI  - Bickerstaff's brainstem encephalitis related to Campylobacter jejuni
      gastroenteritis.

PMID- 17513513
TI  - Sebaceous hyperplasia of the vulva: a clinicopathological case report with a
      review of the literature.

PMID- 17513514
TI  - Pathology sans frontiers.

PMID- 17513515
TI  - Therapy-related, mixed-lineage leukaemia translocation-positive, monoblastic
      myeloid sarcoma of the uterus.
AB  - Myeloid sarcomas are tumour masses of myeloid leukaemic cells at extramedullary
      sites. These tumours can, on occasion, occur without concurrent or antecedent
      leukaemia. Myeloid sarcomas have been described at unusual locations including
      the female genital tract. An unusual case of therapy-related acute myeloid
      leukaemia (t-AML) presenting as isolated monoblastic myeloid sarcoma of the
      uterus in a patient who had received adjuvant chemotherapy for breast cancer is
      presented. Fluorescence in situ hybridisation analysis performed on paraffin-wax
      embedded tumour tissue revealed a mixed-lineage leukaemia (MLL) gene
      rearrangement, supporting the association of this malignancy with prior
      chemotherapy. This case illustrates that t-AML can rarely present as isolated
      extramedullary tumours, and the detection of specific chromosomal abnormalities
      in these myeloid sarcomas can be useful for risk assessment and guiding
      definitive therapy.

PMID- 17513516
TI  - Falsely normal C4 in a case of acquired C1 esterase inhibitor deficiency.
AB  - A 59-year-old lady presented with recurrent angioedema without urticaria. The
      clinical history and examination were consistent with an acquired C1 esterase
      deficiency secondary to lymphoproliferative disease. Despite a low C1 esterase
      level, the C4 level assayed by nephelometry on our automated analyser was normal.
      Analysis using different nephelometric analysers revealed consistently low C4,
      despite consistent normal readings in our analyser. Further investigation
      revealed an IgM-kappa paraprotein that seemed to interfere with both this and
      haematology coagulation assays. Splenic marginal zone lymphoma was confirmed on
      bone marrow biopsy. Monoclonal paraproteins may interfere with nephelometric,
      turbidimetric and immunological assays in a non-antibody-specific manner and
      should be considered when there are unusual or unexpected results, particularly
      in a patient with lymphoproliferative disease.

PMID- 17513517
TI  - A proliferating composite adnexal tumour of the penis: report of the first case.

PMID- 17513518
TI  - Comparison of the clinical utility of atrial and B type natriuretic peptide
      measurement for the diagnosis of systolic dysfunction in a low-risk population.
AB  - BACKGROUND: Measurement of B type natriuretic peptide and its N terminal
      prohormone (NTproBNP) can now be performed routinely by automated high-throughput
      immunoassays. The study compared measurement of NTproBNP with measurement of N
      terminal pro-atrial natriuretic peptide (NTproANP) for detection of ventricular
      systolic dysfunction in primary care. METHODS: 734 subjects aged >45 years (349
      men and 385 women, median age 58 years, range 45-89, interquartile range 51-67
      years) from seven representative general practices attended for echocardiography
      with determination of ejection fraction and completed a questionnaire. Blood
      samples were collected into gel serum separation tubes (Becton-Dickinson,
      Franklin Lakes, New Jersey, USA), the serum separated and aliquots stored frozen
      at -70 degrees C until analyses. Samples were analysed for NTproBNP (Roche
      Diagnostics, Lewes, UK; coefficient of variation (CV) 3.2-2.4%) and for NTproANP
      (Biomedica, Vienna, Austria; CV 5.6-10.1%). Echocardiography was used as the
      diagnostic "gold standard", with ventricular systolic dysfunction defined as
      abnormal when there was an ejection fraction of <or=40%. Patients were
      dichotomised by ejection fraction from 50% to 30%, and receiver operating
      characteristic curves constructed and the area under the curve (AUC) compared.
      RESULTS: At 40% ejection fraction, NTproANP and NTproBNP showed AUCs of,
      respectively, 0.738 (0.601-0.875) and 0.973 (0.958-0.989), p<0.004. CONCLUSION:
      NTproBNP is superior to NTproANP for detection of systolic dysfunction.

PMID- 17513519
TI  - CD5-positive diffuse large B cell lymphoma arising from a CD5-positive follicular
      lymphoma.
AB  - Follicular lymphoma (FL) is a neoplasm originating from germinal centre cells,
      corresponding to 25-40% of non-Hodgkin's lymphomas. Transformation into diffuse
      large B cell lymphoma (DLBCL) occurs in about one-third of cases. CD5 is
      expressed in B-chronic lymphoid leukaemia/small lymphocytic lymphoma and mantle
      cell lymphoma, but can rarely be expressed in conjunction with CD10 in well
      documented cases of FL. In this report one case of grade 1 FL is described, which
      transformed into a DLBCL 6 months after initial diagnosis, with both tumours
      expressing CD5. In both specimens, neoplastic cells were strongly positive for
      CD20, CD79a, bcl-2, bcl-6 and CD5 in virtually all cells. CD10 was strongly
      positive in initial specimens and weakly positive in the DLBCL. Investigation
      using the PCR confirmed the derivation of the DLBCL from the FL as they presented
      the same immunoglobulin heavy chain gene rearrangement and the same BCL2-J(H)
      break point.

PMID- 17513520
TI  - Another case of serrated adenoma of the stomach.

PMID- 17513521
TI  - Paraplegia due to a paravertebral extramedullary haemopoiesis in a patient with
      polycythaemia vera.

PMID- 17513522
TI  - Osseous metaplasia in ovarian tumours: a case with serous cystadenoma.

PMID- 17513523
TI  - Obesity-related glomerulopathy: another nail in the coffin of the epidemic of end
      stage renal disease.

PMID- 17513524
TI  - Catecholamine and metanephrine excess in intracerebral haemorrhage: revisiting an
      obscure yet common "pseudophaeochromocytoma".

PMID- 17513525
TI  - Limitations of transferability of absolute cut-points in non-standardised assays.

PMID- 17513526
TI  - Lengthy appendices.

PMID- 17513527
TI  - Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related
      hearing impairment.
AB  - BACKGROUND: Age-related hearing impairment (ARHI) is the most common sensory
      impairment in older people, affecting 50% of those aged 80 years. The proportion
      of older people is increasing in the general population, and as a consequence,
      the number of people affected with ARHI is growing. ARHI is a complex disorder,
      with both environmental and genetic factors contributing to the disease. The
      first studies to elucidate these genetic factors were recently performed,
      resulting in the identification of the first two susceptibility genes for ARHI,
      NAT2 and KCNQ4. METHODS: In the present study, the association between ARHI and
      polymorphisms in genes that contribute to the defence against reactive oxygen
      species, including GSTT1, GSTM1 and NAT2, was tested. Samples originated from
      seven different countries and were combined into two test population samples, the
      general European population and the Finnish population. Two distinct phenotypes
      for ARHI were studied, Z(low) and Z(high), representing hearing in the low and
      high frequencies, respectively. Statistical analysis was performed for single
      polymorphisms (GSTM1, GSTT1, NAT2*5A, NAT2*6A, and NAT2*7A), haplotypes, and gene
      environment and gene-gene interactions. RESULTS: We found an association between
      ARHI and GSTT1 and GSTM1 in the Finnish population sample, and with NAT2*6A in
      the general European population sample. The latter finding replicates previously
      published data. CONCLUSION: As replication is considered the ultimate proof of
      true associations in the study of complex disorders, this study provides further
      support for the involvement of NAT2*6A in ARHI.

PMID- 17513528
TI  - The novel IFNGR1 mutation 774del4 produces a truncated form of interferon-gamma
      receptor 1 and has a dominant-negative effect on interferon-gamma signal
      transduction.
AB  - BACKGROUND: Patients with interferon-gamma receptor 1 (IFNgammaR1) deficiency
      show selective susceptibility to intracellular pathogens such as mycobacteria.
      IFNgammaR1 deficiency is an inherited immunodeficiency disorder, which can be
      either recessive or dominant. Dominant forms of IFNgammaR1 deficiency are known
      to be associated with mutations that introduce a premature stop codon in the
      intracellular domain of IFNgammaR1. One such mutation, 818del4, is believed to be
      the most common type. Although these mutations are presumed to exert a dominant
      negative effect on IFNgamma signal transduction, the underlying molecular
      mechanism is unresolved. OBJECTIVE: We characterised the 774del4 mutant of
      IFNgammaR1 using a gene-expression system to examine the effects of this mutation
      on IFNgamma signal transduction. RESULTS: We identified a novel dominant mutation
      in IFNGR1, designated 774del4, which produced a truncated form of IFNgammaR1 in a
      patient with recurrent mycobacterial infections. IFNgammaR1 was overexpressed on
      the surfaces of CD14-positive cells from the peripheral blood of this patient,
      and STAT1 phosphorylation in response to high doses of IFNgamma was partially
      deficient. We expressed two truncated forms of IFNgammaR1, 774del4 and 818del4,
      in HEK 293 cells using transient transfection and found that these mutants
      overexpressed IFNgammaR1 on the cell surface because of impaired receptor
      stability, which resulted in a dominant-negative effect on IFNgamma signal
      transduction. CONCLUSION: Like the 818del4 mutation, 774del4 produces a truncated
      form of IFNgammaR1, which has a dominant-negative effect on IFNgamma signal
      transduction through altered receptor stability.

PMID- 17513530
TI  - Impact factors and consent to publish.

PMID- 17513529
TI  - A functional CD86 polymorphism associated with asthma and related allergic
      disorders.
AB  - BACKGROUND: Several studies have documented a substantial genetic component in
      the aetiology of allergic diseases and a number of atopy susceptibility loci have
      been suggested. One of these loci is 3q21, at which linkage to multiple atopy
      phenotypes has been reported. This region harbours the CD86 gene encoding the
      costimulatory B7.2 protein. The costimulatory system, consisting of receptor
      proteins, cytokines and associated factors, activates T cells and regulates the
      immune response upon allergen challenge. METHODS: We sequenced the CD86 gene in
      patients with atopy from 10 families that showed evidence of linkage to 3q21.
      Identified polymorphisms were analysed in a subsequent family-based association
      study of two independent Danish samples, respectively comprising 135 and 100
      trios of children with atopy and their parents. Functional analysis of the
      costimulatory effect on cytokine production was performed in an autologous cell
      based system based on cells expressing CD86 variants. RESULTS: Two polymorphisms
      were identified, encoding the amino acid changes Ile179Val and Ala304Thr,
      respectively. Significant associations were observed between the Ile179Val
      polymorphism and allergy phenotypes in both samples (eg, asthma, p = 4 x 10(-3)
      in the two samples combined). The undertransmitted (protective) Val179 allele was
      found to induce higher production of both Th1 and Th2 cytokines than the
      overtransmitted (risk) Ile179 allele, suggesting a functional impact of the
      polymorphism. CONCLUSION: The CD86 gene, and specifically the Ile179Val
      polymorphism, may be a novel aetiological factor in the development of asthma and
      related allergic disorders.

PMID- 17513531
TI  - Management of macroscopic haematuria in the emergency department.
AB  - Macroscopic haematuria is a commonly seen condition in the emergency department
      (ED), which has a variety of causes. However, most importantly, macroscopic
      haematuria has a high diagnostic yield for urological malignancy. 30% of patients
      presenting with painless haematuria are found to have a malignancy. The majority
      of these patients can be managed in the outpatient setting. This review of
      current literature suggests a management pathway that can be used in the ED. A
      literature search was done using Medline, PubMed and Google. In men aged >60
      years, the positive predictive value of macroscopic haematuria for urological
      malignancy is 22.1%, and in women of the same age it is 8.3%. In terms of the
      need for follow-up investigation, a single episode of haematuria is equally
      important as recurrent episodes. Baseline investigation in the ED includes full
      blood count, urea and electrolyte levels, midstream urine dipstick, beta human
      chorionic gonadotrophin, and formal microscopy, culture and sensitivities.
      Treatment of macroscopic haematuria aims at RESP--Resuscitation, Ensuring, Safe
      and Prompt. Indications for admission include clot retention, cardiovascular
      instability, uncontrolled pain, sepsis, acute renal failure, coagulopathy, severe
      comorbidity, heavy haematuria or social restrictions. Discharged patients should
      drink plenty of clear fluids and return for further medical attention if the
      following occur: clot retention, worsening haematuria despite adequate fluid
      intake, uncontrolled pain or fever, or inability to cope at home. Follow-up by a
      urological team should be promptly arranged, ideally within the 2-week cancer
      referral target.

PMID- 17513532
TI  - How much do emergency healthcare workers know about capacity and consent?
AB  - AIM: To assess knowledge of capacity and consent among emergency healthcare
      workers. DESIGN: A cross-sectional survey with a structured questionnaire.
      METHODS: 86 questionnaires were distributed and completed by 42 accident and
      emergency doctors, 21 accident and emergency nurses, and 23 emergency ambulance
      staff. Correct answers on assessing capacity to consent to or refuse treatment
      were given by 67% of the doctors and 10% of the nurses, but by none of the
      ambulance workers. 15% of all respondents wrongly believed that an adult who is
      found to have capacity can lawfully be treated against his or her will.
      CONCLUSIONS: The results of this study indicate that emergency healthcare workers
      do not have adequate knowledge about how to assess capacity and treat people who
      either refuse treatment or lack capacity. It shows a need for further training
      among doctors, nurses and ambulance staff working in the emergency setting.

PMID- 17513533
TI  - Tracheal intubation in the emergency department: the Scottish district hospital
      perspective.
AB  - BACKGROUND: Tracheal intubation is the accepted gold standard for emergency
      department (ED) airway management. It may be performed by both anaesthetists and
      emergency physicians (EPs), with or without drugs. OBJECTIVE: To characterise
      intubation practice in a busy district general hospital ED in Scotland over 40
      months between 2003 and 2006. SETTING: Crosshouse Hospital, a 450-bed district
      general hospital serving a mixed urban and rural population; annual ED census
      58,000 patients. METHODS: Prospective observational study using data collection
      sheets prepared by the Scottish Trauma Audit Group. Proformas were completed at
      the time of intubation and checked by investigators. Rapid-sequence induction
      (RSI) was defined as the co-administration of an induction agent and
      suxamethonium. RESULTS: 234 intubations over 40 months, with a mean of 6 per
      month. EPs attempted 108 intubations (46%). Six patients in cardiac arrest on
      arrival were intubated without drugs. 29 patients were intubated after a gas
      induction or non-RSI drug administration. RSI was performed on 199 patients.
      Patients with trauma constituted 75 (38%) of the RSI group. 29 RSIs (15%) were
      immediate (required on arrival at the ED) and 154 (77%) were urgent (required
      within 30 min of arrival at the ED). EPs attempted RSI in 88 (44%) patients and
      successfully intubated 85 (97%). Anaesthetists attempted RSI in 111 (56%)
      patients and successfully intubated 108 (97%). Anaesthetists had a higher
      proportion of good views at first laryngoscopy and there was a trend to a higher
      rate of successful intubation at the first attempt for anaesthetists.
      Complication rates were comparable for the two specialties. CONCLUSIONS: Tracheal
      intubations using RSI in the ED are performed by EPs almost as often as by
      anaesthetists in this district hospital. Overall success and complication rates
      are comparable for the two specialties. Laryngoscopy training and the need to
      achieve intubation at the first (optimum) attempt needs to be emphasised in EP
      airway training.

PMID- 17513534
TI  - Defining frequent use of an urban emergency department.
AB  - OBJECTIVE: This study aimed to develop a definition of frequent use of an
      emergency department (ED) by comparing differences in the observed frequency
      distribution with that of a theoretical frequency distribution. METHODS: A
      retrospective analysis of attendance of ED and minor injury unit attendances in
      one city over 1 year was conducted. From these data, the expected frequency
      distribution was determined based upon a Poisson distribution. RESULTS: During
      the period studied, 75,141 people attended on 98,908 occasions. The theoretical
      frequency distribution showed that there were 2764 (3.7%) "frequent users"
      presenting repeatedly due to non-random events. These patients made 12,316
      (12.4%) attendances. Frequent users were older than chance users (mean age 49.7
      vs 44.5 years). A greater proportion arrived by ambulance (55.3% vs 27.5%),
      presented with psychiatric problems (5.8% vs 1.1%) or alcohol intoxication (1.3%
      vs 0.5%), and were admitted to hospital (37.4% vs 19.6%). CONCLUSION: We have
      identified that there is a group of patients who present repeatedly due to non
      random events, confirming the existence of "frequent users". Their
      characteristics are clearly different to other patients in the ED. We propose
      that "frequent users" be defined as any patient who makes more than four
      attendances per year.

PMID- 17513535
TI  - The "4-hour target": emergency nurses' views.
AB  - OBJECTIVE: To explore nurses' views and to identify the perceived advantages and
      disadvantages of the "4-hour target." METHODS: The study was based in one
      emergency department (ED) in the UK and took a generic qualitative approach. A
      stratified sample of nine experienced ED nurses were recruited for semi
      structured interviews. Data was analysed using the framework analysis approach.
      RESULTS: The 4-hour target was considered an overall success in reducing waiting
      times and increasing patient satisfaction. However, staff expressed concerns over
      the imposed nature of the target, workload pressures, quality of care, and the
      level of support from secondary and primary care. CONCLUSION: Although deemed an
      overall success, there were reservations as to the target's sustainability.
      Recommendations are made for improved communication between primary and secondary
      care and establishing the target as a shared goal within the hospital
      environment.

PMID- 17513536
TI  - Effects of international football matches on ambulance call profiles and volumes
      during the 2006 World Cup.
AB  - BACKGROUND: Prompt ambulance attendance is aimed at improving patient care. With
      finite resources struggling to meet performance targets, unforeseen demand
      precludes the ability to tailor resources to cope with increased call volumes,
      and can have a marked detrimental effect on performance and hence patient care.
      The effects of the 2006 World Cup football matches on call volumes and profiles
      were analysed to understand how public events can influence demands on the
      ambulance service. METHODS: All emergency calls to the Hampshire Ambulance
      Service NHS Trust (currently the Hampshire Division of South Central Ambulance
      Service, Winchester, UK) during the first weekend of the 2006 World Cup football
      matches were analysed by call volume and classification of call (call type).
      RESULTS: On the day of the first football match, call volume was over 50% higher
      than that on a typical Saturday, with distinct peaks before and after the
      inaugural match. Call profile analysis showed increases in alcohol-related
      emergencies, including collapse, unconsciousness, assault and road traffic
      accidents. The increase in assaults was particularly marked at the end of each
      match and increased again into the late evening. CONCLUSION: A detailed mapping
      of call volumes and profiles during the World Cup football shows a significant
      increase in overall emergency calls, mostly alcohol related. Mapping of limited
      resources to these patterns will allow improved responses to emergency calls.

PMID- 17513537
TI  - A randomised controlled trial to test the analgesic efficacy of topical morphine
      on minor superficial and partial thickness burns in accident and emergency
      departments.
AB  - OBJECTIVES: To test the analgesic efficacy of topical morphine on superficial
      burns within the emergency department by comparing pain scores, comfort ratings
      and analgesia taken by participants. METHOD: A placebo-controlled three-treatment
      randomised controlled trial was undertaken. 59 participants were randomly
      allocated to receive a dressing containing Intrasite gel and morphine sulphate,
      Intrasite gel and water or the conventional Jelonet dressing. The study design
      enabled double-blinding between the two Intrasite gel treatments. RESULTS: 49
      participants were included in the final analysis as 10 were lost to follow-up. No
      significant differences were observed between the pain scores or comfort ratings
      of the three treatments. Participants receiving Jelonet and the placebo reduced
      their pain scores by the greatest amount overall. However, participants receiving
      morphine were the only group to reduce pain scores by >20 mm on two consecutive
      time intervals (2 and 6 h). At 12 h the morphine group reported the highest pain
      scores. Only 4/15 participants receiving topical morphine administered additional
      analgesia compared with 12/17 receiving the Jelonet dressing and 6/17 receiving
      Intrasite and water (p = 0.055). However, when all analgesia was taken into
      account, the morphine group was administered the greatest amount. Overall, the
      placebo group reported their dressings to be the most comfortable and took the
      least amount of analgesia. Minor adverse reactions included itching, burning and
      a rash. No serious adverse reactions were reported. CONCLUSIONS: Topical morphine
      sulphate does not seem to be as effective when used for the pain associated with
      superficial burns as when used for the pain associated with chronic inflammatory
      wounds. (The European Clinical Trials Database number for this study is 2005
      003285-42.).

PMID- 17513538
TI  - A model for teaching bedside detection of glass in wounds.
AB  - BACKGROUND: Emergency physicians often manage wounds contaminated with glass.
      Even when glass is visible on x rays, removal may require real-time bedside
      imaging. AIM: To assess whether novices can be easily trained to accurately
      detect tiny glass foreign bodies (GFBs) using low-power portable fluoroscopy.
      METHODS: 21 medical students with no prior experience using fluoroscopy were
      taught to detect 1 mm GFBs in chicken legs either by training over three separate
      days or by training on 1 day. Skills were reassessed at 3 months. The number of
      mean correct responses was compared between groups using analysis of variance
      (ANOVA) and by examination of 95% CIs. RESULTS: Examination of CI overlap and
      ANOVA suggested that asymptotic accuracy was achieved after 15-30 training
      specimens. The final accuracy was similar between protocols, was comparable to
      prior accuracy reports of plain film radiography and was maintained in both
      protocols at the 3 month follow-up: 10.9 (0.3) and 12.0 (0.8; out of 15).
      CONCLUSIONS: Novices can easily be taught to detect GFBs using fluoroscopy, with
      accuracy comparable to that achieved by radiologists using plain films. Further
      studies are needed to assess doctors' use of the technique in real patients.

PMID- 17513539
TI  - Audit of tetanus prevention knowledge and practices in accident and emergency
      departments in England.
AB  - OBJECTIVES: To assess the knowledge and current tetanus prevention practices of
      various staff members in accident and emergency (A&E) departments. DESIGN,
      SETTING AND PARTICIPANTS: A structured questionnaire containing 16 questions on
      tetanus guidance, anti-tetanus practice, vaccination preparations and information
      on the population served by the department was sent to medical and nursing staff
      in A&E departments across England. RESULTS: 366 completed questionnaires from 67
      hospitals were returned. 48.9% of the questionnaires were completed by the
      medical staff and 39.9% by the nursing staff at various grades. 75% of
      respondents said that their department had a local tetanus guideline, but only
      29% stated that the tetanus guidelines were always followed. 31.4% of respondents
      said that injecting drug users were managed as a high-risk group in their
      department. Many respondents did not follow the national policy; they tended to
      err on the side of caution when it came to defining and treating tetanus-prone
      wounds, with 22.1% stating that they would consider any wound tetanus prone.
      Contrary to current Department of Health guidelines, 46.2% of respondents said
      that they would give a booster dose if the fifth dose had been given >10 years
      ago. CONCLUSIONS: There are clear differences between the recommended guidelines
      for tetanus prevention and current practice in A&E departments. The changes
      announced in 2002 do not seem to have been widely implemented. As a result, the
      apparent success of the national tetanus vaccination programme may be the result
      of more cautious clinical practice than would be expected from the UK policy. If
      national recommendations for tetanus are implemented in clinical practice, then
      the impact on control of the disease should be monitored closely.

PMID- 17513540
TI  - Management of severe sepsis and septic shock in the emergency department: a
      survey of current practice in emergency departments in England.
AB  - AIM: To identify the extent to which emergency departments (EDs) in England are
      involved in the initiation of the pathway to early goal-directed therapy (EGDT)
      in patients with severe sepsis and septic shock. METHOD: A survey of 173 EDs in
      England was carried out over a 2-month period starting in March 2006. RESULTS:
      117 (67.6%) departments responded. 22 (18.8%) departments satisfied the following
      criteria: had a strategy to identify these patients, measured lactate, had a
      written protocol including EGDT and provided training for their staff. A further
      10 (8.5%) EDs were working on initiating the pathway to EGDT. CONCLUSION: 18.8%
      of EDs in England are able to initiate the pathway to EGDT in patients with
      severe sepsis and septic shock.

PMID- 17513541
TI  - Administering a glyceryl trinitrate infusion: big is not always best.
AB  - With the use of some simple calculations it can be demonstrated that the choice
      of cannula and initial glyceryl trinitrate (GTN) infusion rate for patients with
      acute left ventricular failure (LVF) requires some careful thought. If a GTN
      infusion is commenced at a rate of 1 ml/h, a critically unwell patient with a
      large cannula--for example, a grey cannula--will have to wait over 6 min for the
      drug to enter the body. This compares with 1.5 min for a pink cannula at the same
      infusion rate. If a large-diameter cannula is chosen for these patients, then a
      fast initial infusion rate should also be chosen to ensure that the GTN begins to
      act quickly. The rate can later be adjusted depending on clinical conditions.

PMID- 17513543
TI  - The use of an asynchronous learning network for senior house officers in
      emergency medicine.
AB  - Full-shift working by senior house officers (SHOs) is well recognised as a
      definite constraint to effective group learning, as it is practically impossible
      to gather all team members together for teaching sessions at any given time.
      Provision of a robust weekly teaching programme is further compromised in units
      where relatively few doctors participate in the rota in any case. Although
      practical skills tuition will always demand an intensive, hands-on learning
      environment, teaching in relation to case-based discussion, clinical problem
      solving and other group activities may well be suited to more innovative methods.

PMID- 17513542
TI  - Abstract-to-publication ratio for papers presented at scientific meetings: a
      quality marker for UK emergency medicine research.
AB  - OBJECTIVES: To determine the publication rate of abstracts presented by UK
      emergency physicians at major emergency medicine meetings, and to identify the
      site of publication of papers. METHOD: All abstracts presented to the annual
      scientific meetings of both the British Association of Emergency Medicine and the
      Faculty of Accident and Emergency Medicine between 2001 and 2002 were identified
      retrospectively from conference programmes. To identify whether the work relating
      to the abstract had been published in a peer-reviewed journal, the Medline
      database (Ovid interface) was searched using the first and last authors as well
      as key words from the abstract. RESULTS: Of the 404 abstracts identified, 124
      (30%) had been published as full articles. For abstracts presented in the oral
      sessions, 83 (57%) resulted in publication. A range of journals accepted papers
      for publication. CONCLUSION: The abstract-to-publication ratio for UK emergency
      medicine is lower than for other specialties, but broadly similar to emergency
      medicine in the US and Australia.

PMID- 17513544
TI  - Diagnosis and management of common maxillofacial injuries in the emergency
      department. Part 5: Dentoalveolar injuries.
AB  - Injuries to teeth can be very distressing for patients. Prompt treatment is
      essential. Injuries of the tooth bearing portion of the mandible are common and
      can even result after a relatively low impact trauma. The alveolus (tooth bearing
      portion of bone) and/or the tooth may be damaged. Segmental fractures involve
      multiple teeth and the supporting alveolar bone.

PMID- 17513545
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Serum lactate as a marker for mortality in patients presenting to the
      emergency department with infection.

PMID- 17513547
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Negative D-dimer may allow safe early cardioversion of atrial
      fibrillation.

PMID- 17513548
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Does clopidogrel increase morbidity and mortality after minor head
      injury.

PMID- 17513549
TI  - Prehospital anaesthesia in the UK: position statement.
AB  - Prehospital anaesthesia is carried out regularly by a small number of prehospital
      care practitioners in the UK. Although mostly predictable, prehospital disorders
      can be more difficult than those in hospital, and, in addition, peer and skilled
      anaesthetic assistance is usually not available. Hence, patient safety should be
      given paramount importance, and systems need to be in place to ensure that the
      highest standards are achieved.

PMID- 17513551
TI  - Cavernous sinus thrombophlebitis masquerading as ischaemic stroke: a catastrophic
      pitfall in any emergency department.
AB  - Cavernous sinus thrombophlebitis is a clinically rare but fatal disease that
      progresses rapidly. Its initial presentation is always neglected by emergency
      physicians, until typical symptoms and signs are noted or thin-slice brain CT
      results obtained, by which time it is already too late. A case of cavernous sinus
      thrombophlebitis caused by sinusitis, which initially masqueraded as ischaemic
      stroke, is reported. Blindness of the left eye was the outcome. High suspicion,
      accurate diagnosis and aggressive antibiotic treatment are emphasised.

PMID- 17513552
TI  - Paradoxical embolus illustrating speed of action of recombinant tissue
      plasminogen activator in massive pulmonary embolism.
AB  - A case of a patient who presented with massive pulmonary embolism (PE) requiring
      thrombolysis with alteplase is reported. The subsequent presence of a patent
      foramen ovale and paradoxical embolism clinically demonstrated the speed of
      action of the recombinant tissue plasminogen activator. The advantage of this
      class of medication when considering the treatment options for a PE in an acute
      setting is highlighted.

PMID- 17513553
TI  - An unusual case of infective endocarditis presenting as acute myocardial
      infarction.
AB  - A 39-year-old Zimbabwean man presented with a 1 week history of fever, general
      malaise and acute-onset chest pain. He had a urethral stricture, which had been
      managed with an indwelling supra-pubic catheter. The electrocardiography on
      admission showed inferior ST-T segments elevation. His chest pain and
      electrocardiography changes resolved subsequent to thrombolysis, and he remained
      haemodynamically stable. The 12-h troponin I was increased at 10.5 microg/l (NR
      <0.04 microg/l). Echocardiography confirmed severe mitral regurgitation and a
      flail anterior mitral valve leaflet with an independently oscillating mobile
      vegetation. Enterococci faecalis were grown on blood cultures. A diagnosis of
      enterococci infective endocarditis with concomitant acute myocardial infarction
      due to possible septic emboli was made. Despite the successful outcome from
      thrombolysis in the setting of acute myocardial infarction with infective
      endocarditis, the case highlights the current lack of definitive data on the
      optimal acute management of such an unusual clinical scenario. Although there is
      serious concern that thrombolytic treatment for myocardial infarction in the
      setting of infective endocarditis may be associated with higher risk of cerebral
      haemorrhage, there is little documented evidence supporting the safety of primary
      percutaneous coronary intervention with these patients.

PMID- 17513554
TI  - The diagnosis and management of transient global amnesia in the emergency
      department.
AB  - Transient Global Amnesia (TGA) is a benign and temporary loss of anterograde
      memory with the preservation of remote memories and immediate recall. TGA was
      first described in 1956 and since then epilepsy, transient ischaemic attacks
      (TIA), migraine and now intracranial venous stasis have been implicated in its
      aetiology. Precipitants of TGA include physical exertion and valsalva-like
      manoeuvres. In order to diagnose TGA the criteria created by Hodge and Warlow in
      1990 can be used. This requires the episode of memory loss to be witnessed and
      involve anterograde amnesia. The patient must not have any evidence of
      neurological signs or deficits, features of epilepsy, active epilepsy or recent
      head injury. Finally the episode must have resolved within 24 h. In this case
      study the patient's symptoms are mistakenly attributed to a TIA. There is no
      increased risk of TIA or CVA in patients who have had TGA and there are no
      increased levels of mortality amongst these patients. In this article we aim to
      help doctors working in the emergency department to diagnose and manage TGA.

PMID- 17513555
TI  - Gastric volvulus.
AB  - Gastric volvulus is a rare disease with an unknown incidence. Unless it stays in
      the back of the diagnostician's mind, diagnosis of gastric volvulus, which can
      have significant morbidity and mortality associated with it, can be easily
      missed. Unstable vital signs and distressed appearance are not always present, as
      in textbook cases. The presence of a hiatal hernia with persistent vomiting
      despite initial antiemetic treatment should trigger one to think of gastric
      volvulus, despite the patient appearing very stable. With the advent of CT and
      laparoscopic surgery, the gold standards for diagnosing and treating this disease
      are ever evolving.

PMID- 17513556
TI  - Lamotrigine rash--a potentially life-threatening complication.

PMID- 17513557
TI  - Persistent flank pain without active urinary sediments.

PMID- 17513558
TI  - An unusual symptom of cystic teratoma cases.

PMID- 17513559
TI  - Prehospital and retrieval medicine.

PMID- 17513560
TI  - Anti-tumor effect of endostatin mediated by retroviral gene transfer in mice
      bearing renal cell carcinoma.
AB  - We investigated whether transfer of the gene encoding the angiogenesis inhibitor
      endostatin into the NIH/3T3 fibroblast cell line could inhibit renal tumor growth
      in vivo. NIH/3T3 cells were transduced with retroviral vectors containing the
      murine endostatin (ES) gene. SCID mice bearing CaKi-1 derived tumors were given a
      subcutaneous injection of either ES-transduced cells or control cells and were
      monitored for tumor growth. At the end of the in vivo experiment, the mean tumor
      volume of treated mice was 51.6 +/- 2.4 mm3, while the tumor volume of control
      was 234.5 +/- 14.8 mm3. Microvascular density was significantly decreased on
      treatment (control 9.79 vs. ES 2.53%, <0.001) accompanied by a 23-fold increase
      in intratumoral necrotic area and a 2.94-fold increase in the apoptotic index,
      determined by immunohistochemistry with anti-activated caspase-3. Apoptotic cells
      were found in foci enriched in infiltrating leukocytes. In conclusion, retroviral
      endostatin gene transfer led to secretion of functional endostatin that was
      sufficiently active to inhibit tumor angiogenesis and tumor growth. A second
      mechanism may also be implied in endostatin-dependent tumor regression,
      associated with tumor infiltration of leukocytes. Besides its antiangiogenic
      properties, endostatin may be a promising adjuvant to immunotherapy.

PMID- 17513561
TI  - Treatment of hypoxia-induced retinopathy with targeted proapoptotic
      peptidomimetic in a mouse model of disease.
AB  - We have previously identified ligands from combinatorial peptide libraries that
      target tumor vasculature after in vivo selection. These ligands bind to
      differentially expressed receptors in angiogenic vasculature such as
      alpha(v)beta3/alpha(v)beta5 integrins, aminopeptidase N, and aminopeptidase A. We
      hypothesized that we can use these ligands to target angiogenic vasculature in
      retinopathies. Pathological retinal angiogenesis in conditions such as diabetic
      retinopathy, retinopathy of prematurity, and age-related macular degeneration is
      a major cause of blindness for which current treatments are inadequate. Here we
      tested whether known tumor vasculature targeting peptide ligands displayed on
      bacteriophage particles would home to the proliferating blood vessels of the
      retina in a standard mouse model of retinopathy of prematurity. We found that
      activated retinal blood vessels share many of the endothelial and periendothelial
      cell receptors expressed in tumor vasculature. Furthermore, these vascular
      receptors--alpha(v) integrins and aminopeptidases--are accessible through the
      circulation and mediate phage homing and internalization to endothelial and
      periendothelial cells. Treatment of mice with a peptide containing a
      alpha(v)beta3/alpha(v)beta5-integrin targeting domain fused to a proapoptotic
      domain significantly reduced oxygen-induced retinal angiogenesis by selectively
      inducing activated endothelial cell apoptosis. Targeted proapoptotic peptides may
      prove useful in the management of angiogenic retinal diseases.

PMID- 17513562
TI  - Split-ubiquitin two-hybrid assay to analyze protein-protein interactions at the
      endosome: application to Saccharomyces cerevisiae Bro1 interacting with ESCRT
      complexes, the Doa4 ubiquitin hydrolase, and the Rsp5 ubiquitin ligase.
AB  - Targeting of membrane proteins into the lysosomal/vacuolar lumen for degradation
      requires their prior sorting into multivesicular bodies (MVB). The MVB sorting
      pathway depends on ESCRT-0, -I, -II, and -III protein complexes functioning on
      the endosomal membrane and on additional factors, such as Bro1/Alix and the
      ubiquitin ligase Rsp5/Nedd4. We used the split-ubiquitin two-hybrid assay to
      analyze the interaction partners of yeast Bro1 at its natural cellular location.
      We show that Bro1 interacts with ESCRT-I and -III components, including Vps23,
      the Saccharomyces cerevisiae homologue of human Tsg101. These interactions do not
      require the C-terminal proline-rich domain (PRD) of Bro1. Rather, this PRD
      interacts with the Doa4 deubiquitinating enzyme to recruit it to the endosome.
      This interaction is disrupted by a single amino acid substitution in the
      conserved ELC box motif in Doa4. The PRD of Bro1 also mediates an association
      with Rsp5, and this interaction appears to be conserved, as Alix, the human
      homologue of Bro1, coimmunoprecipitates with Nedd4 in yeast lysates. We further
      show that the Bro1 PRD domain is essential to MVB sorting of only cargo proteins
      whose sorting to the vacuolar lumen is dependent on their own ubiquitination and
      Doa4. The Bro1 region preceding the PRD, however, is required for MVB sorting of
      proteins irrespective of whether their targeting to the vacuole is dependent on
      their ubiquitination and Doa4. Our data indicate that Bro1 interacts with several
      ESCRT components and contributes via its PRD to associating ubiquitinating and
      deubiquitinating enzymes with the MVB sorting machinery.

PMID- 17513563
TI  - Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a
      potent inhibitor of amebic invasion in a human colonic model.
AB  - Cysteine proteinases are key virulence factors of the protozoan parasite
      Entamoeba histolytica. We have shown that cysteine proteinases play a central
      role in tissue invasion and disruption of host defenses by digesting components
      of the extracellular matrix, immunoglobulins, complement, and cytokines. Analysis
      of the E. histolytica genome project has revealed more than 40 genes encoding
      cysteine proteinases. We have focused on E. histolytica cysteine proteinase 1
      (EhCP1) because it is one of two cysteine proteinases unique to invasive E.
      histolytica and is highly expressed and released. Recombinant EhCP1 was expressed
      in Escherichia coli and refolded to an active enzyme with a pH optimum of 6.0. We
      used positional-scanning synthetic tetrapeptide combinatorial libraries to map
      the specificity of the P1 to P4 subsites of the active site cleft. Arginine was
      strongly preferred at P2, an unusual specificity among clan CA proteinases. A new
      vinyl sulfone inhibitor, WRR483, was synthesized based on this specificity to
      target EhCP1. Recombinant EhCP1 cleaved key components of the host immune system,
      C3, immunoglobulin G, and pro-interleukin-18, in a time- and dose-dependent
      manner. EhCP1 localized to large cytoplasmic vesicles, distinct from the sites of
      other proteinases. To gain insight into the role of secreted cysteine proteinases
      in amebic invasion, we tested the effect of the vinyl sulfone cysteine proteinase
      inhibitors K11777 and WRR483 on invasion of human colonic xenografts. The
      resultant dramatic inhibition of invasion by both inhibitors in this human
      colonic model of amebiasis strongly suggests a significant role of secreted
      amebic proteinases, such as EhCP1, in the pathogenesis of amebiasis.

PMID- 17513564
TI  - Characterization of three classes of membrane proteins involved in fungal azole
      resistance by functional hyperexpression in Saccharomyces cerevisiae.
AB  - The study of eukaryotic membrane proteins has been hampered by a paucity of
      systems that achieve consistent high-level functional protein expression. We
      report the use of a modified membrane protein hyperexpression system to
      characterize three classes of fungal membrane proteins (ABC transporters Pdr5p,
      CaCdr1p, CaCdr2p, CgCdr1p, CgPdh1p, CkAbc1p, and CneMdr1p, the major facilitator
      superfamily transporter CaMdr1p, and the cytochrome P450 enzyme CaErg11p) that
      contribute to the drug resistance phenotypes of five pathogenic fungi and to
      express human P glycoprotein (HsAbcb1p). The hyperexpression system consists of a
      set of plasmids that direct the stable integration of a single copy of the
      expression cassette at the chromosomal PDR5 locus of a modified host
      Saccharomyces cerevisiae strain, ADDelta. Overexpression of heterologous proteins
      at levels of up to 29% of plasma membrane protein was achieved. Membrane proteins
      were expressed with or without green fluorescent protein (GFP), monomeric red
      fluorescent protein, His, FLAG/His, Cys, or His/Cys tags. Most GFP-tagged
      proteins tested were correctly trafficked within the cell, and His-tagged
      proteins could be affinity purified. Kinetic analysis of ABC transporters
      indicated that the apparent K(m) value and the V(max) value of ATPase activities
      were not significantly affected by the addition of His tags. The efflux
      properties of seven fungal drug pumps were characterized by their substrate
      specificities and their unique patterns of inhibition by eight xenobiotics that
      chemosensitized S. cerevisiae strains overexpressing ABC drug pumps to
      fluconazole. The modified hyperexpression system has wide application for the
      study of eukaryotic membrane proteins and could also be used in the
      pharmaceutical industry for drug screening.

PMID- 17513565
TI  - Protein trafficking to the apicoplast: deciphering the apicomplexan solution to
      secondary endosymbiosis.

PMID- 17513566
TI  - Genomic and population analyses of the mating type loci in Coccidioides species
      reveal evidence for sexual reproduction and gene acquisition.
AB  - Coccidioides species, the fungi responsible for the valley fever disease, are
      known to reproduce asexually through the production of arthroconidia that are the
      infectious propagules. The possible role of sexual reproduction in the survival
      and dispersal of these pathogens is unexplored. To determine the potential for
      mating of Coccidioides, we analyzed genome sequences and identified mating type
      loci characteristic of heterothallic ascomycetes. Coccidioides strains contain
      either a MAT1-1 or a MAT1-2 idiomorph, which is 8.1 or 9 kb in length,
      respectively, the longest reported for any ascomycete species. These idiomorphs
      contain four or five genes, respectively, more than are present in the MAT loci
      of most ascomycetes. Along with their cDNA structures, we determined that all
      genes in the MAT loci are transcribed. Two genes frequently found in common
      sequences flanking MAT idiomorphs, APN2 and COX13, are within the MAT loci in
      Coccidioides, but the MAT1-1 and MAT1-2 copies have diverged dramatically from
      each other. Data indicate that the acquisition of these genes in the MAT loci
      occurred prior to the separation of Coccidioides from Uncinocarpus reesii. An
      analysis of 436 Coccidioides isolates from patients and the environment indicates
      that in both Coccidioides immitis and C. posadasii, there is a 1:1 distribution
      of MAT loci, as would be expected for sexually reproducing species. In addition,
      an analysis of isolates obtained from 11 soil samples demonstrated that at three
      sampling sites, strains of both mating types were present, indicating that
      compatible strains were in close proximity in the environment.

PMID- 17513568
TI  - RNA interference mutant induction in vivo demonstrates the essential nature of
      trypanosome flagellar function during mammalian infection.
AB  - We demonstrate that trypanosomes compromised in flagellar function are rapidly
      cleared from infected mice. Analysis of the PFR2 bloodstream RNA interference
      mutant revealed that defective cell motility occurred prior to cytokinesis
      failure. This validation provides a paradigm for the flagellum as a target for
      future assays and interventions against this human pathogen.

PMID- 17513567
TI  - Development of a highly efficient gene targeting system induced by transient
      repression of YKU80 expression in Candida glabrata.
AB  - In the pathogenic yeast Candida glabrata, gene targeting to generate knockouts
      and "knockins" is a potentially powerful method for the analysis of gene
      function. Its importance increased after the C. glabrata genome sequence project,
      but progress in the field is hampered by inefficient mechanisms for gene
      targeting. With the use of 40-bp homologous flanking DNA, no gene targeting was
      identified. To address this issue, YKU80 was disrupted, leading to an increase in
      targeting efficiency of 5.1% using 40-bp flanking homologous DNA. To harness the
      beneficial effects of YKU80 inactivation on gene targeting frequency without
      incurring any negative effects, such as synthetic sickness or lethality, we
      developed a new system whereby the expression of YKU80 was restored following a
      transient knockdown of expression during transformation. Strains used for this
      new system carried a SAT1 flipper in the YKU80 promoter region, which was used to
      repress expression during transformation but was spontaneously excised from the
      locus after the transformation. By using this strain, DNA damage induced by
      methyl methane sulfonate, H(2)O(2), UV irradiation, and hydroxyurea before and
      during gene targeting was evaluated and the mutation rate of URA3 was determined.
      No significant effects of the SAT1 flipper on these processes have been
      identified. After the SAT1 flipper is excised, a 34-bp FLP recombination target
      sequence is left in the promoter region. However, the levels of mRNA
      transcription were restored and no difference in the survival ratio in vivo
      compared to that with the YKU80 wild-type strain was identified.

PMID- 17513569
TI  - Tumour necrosis factor blockers and structural remodelling in ankylosing
      spondylitis: what is reality and what is fiction?

PMID- 17513570
TI  - Rheumatoid arthritis in Dubai--delayed diagnosis and low usage of disease
      modifying antirheumatic drugs.

PMID- 17513571
TI  - Cardiotoxicity of imatinib mesylate: an extremely rare phenomenon or a major side
      effect?

PMID- 17513572
TI  - Audit on the uptake of influenza and pneumococcal vaccination in patients with
      rheumatoid arthritis.

PMID- 17513573
TI  - N-terminal prohormone brain natriuretic peptide: a biomarker for detecting
      cardiovascular risks in patients with rheumatoid arthritis or osteoarthritis?

PMID- 17513574
TI  - Anakinra treatment in patients with adult-onset Still's disease is fast,
      effective, safe and steroid sparing: experience from an uncontrolled trial.

PMID- 17513575
TI  - Cryopyrin-associated autoinflammatory syndrome: a new mutation.

PMID- 17513576
TI  - DNA microarray analysis of labial salivary glands of patients with Sjogren's
      syndrome.

PMID- 17513577
TI  - Intrathecal immunoglobulin production in patients with systemic lupus
      erythematosus with neuropsychiatric manifestations.

PMID- 17513578
TI  - Core components of cardiac rehabilitation/secondary prevention programs: 2007
      update: a scientific statement from the American Heart Association Exercise,
      Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical
      Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention,
      and Nutrition, Physical Activity, and Metabolism; and the American Association of
      Cardiovascular and Pulmonary Rehabilitation.
AB  - The American Heart Association and the American Association of Cardiovascular and
      Pulmonary Rehabilitation recognize that all cardiac rehabilitation/secondary
      prevention programs should contain specific core components that aim to optimize
      cardiovascular risk reduction, foster healthy behaviors and compliance to these
      behaviors, reduce disability, and promote an active lifestyle for patients with
      cardiovascular disease. This update to the previous statement presents current
      information on the evaluation, interventions, and expected outcomes in each of
      the core components of cardiac rehabilitation/secondary prevention programs, in
      agreement with the 2006 update of the American Heart Association/American College
      of Cardiology Secondary Prevention Guidelines, including baseline patient
      assessment, nutritional counseling, risk factor management (lipids, blood
      pressure, weight, diabetes mellitus, and smoking), psychosocial interventions,
      and physical activity counseling and exercise training.

PMID- 17513580
TI  - Highly efficient gluten degradation by lactobacilli and fungal proteases during
      food processing: new perspectives for celiac disease.
AB  - Presently, the only effective treatment for celiac disease is a life-long gluten
      free diet. In this work, we used a new mixture of selected sourdough lactobacilli
      and fungal proteases to eliminate the toxicity of wheat flour during long-time
      fermentation. Immunological (R5 antibody-based sandwich and competitive enzyme
      linked immunosorbent assay [ELISA] and R5 antibody-based Western blot), two
      dimensional electrophoresis, and mass spectrometry (matrix-assisted laser
      desorption ionization-time of flight, strong-cation-exchange-liquid
      chromatography/capillary liquid chromatography-electrospray ionization-quadrupole
      time of flight [SCX-LC/CapLC-ESI-Q-TOF], and high-pressure liquid chromatography
      electrospray ionization-ion trap mass spectrometry) analyses were used to
      determine the gluten concentration. Assays based on the proliferation of
      peripheral blood mononuclear cells (PBMCs) and gamma interferon production by
      PBMCs and intestinal T-cell lines (iTCLs) from 12 celiac disease patients were
      used to determine the protein toxicity of the pepsin-trypsin digests from
      fermented wheat dough (sourdough). As determined by R5-based sandwich and
      competitive ELISAs, the residual concentration of gluten in sourdough was 12 ppm.
      Albumins, globulins, and gliadins were completely hydrolyzed, while ca. 20% of
      glutenins persisted. Low-molecular-weight epitopes were not detectable by SCX
      LC/CapLC-ESI-Q-TOF mass spectrometry and R5-based Western blot analyses. The
      kinetics of the hydrolysis of the 33-mer by lactobacilli were highly efficient.
      All proteins extracted from sourdough activated PBMCs and induced gamma
      interferon production at levels comparable to the negative control. None of the
      iTCLs demonstrated immunoreactivity towards pepsin-trypsin digests. Bread making
      was standardized to show the suitability of the detoxified wheat flour. Food
      processing by selected sourdough lactobacilli and fungal proteases may be
      considered an efficient approach to eliminate gluten toxicity.

PMID- 17513579
TI  - Development of experimental genetic tools for Campylobacter fetus.
AB  - Molecular analysis of the virulence mechanisms of the emerging pathogen
      Campylobacter fetus has been hampered by the lack of genetic tools. We report the
      development and functional analysis of Escherichia coli-Campylobacter shuttle
      vectors that are appropriate for C. fetus. Some vectors were constructed based on
      the known Campylobacter coli plasmid pIP1455 replicon, which confers a wide host
      range in Campylobacter spp. Versatility in directing gene expression was achieved
      by introducing a strong C. fetus promoter. The constructions carry features
      necessary and sufficient to detect the expression of phenotypic markers,
      including molecular reporter genes in both subspecies of C. fetus, while
      retaining function in C. jejuni. The capacity to express several gene products
      from different vectors in a single host can be advantageous but requires distinct
      plasmid replicons. To this end, replication features derived from a cryptic
      plasmid of C. fetus subsp. venerealis strain 4111/108, designated pCFV108, were
      adapted for a compatible series of constructions. The substitution of the C. coli
      replication elements reduced vector size while apparently limiting the host range
      to C. fetus. The complementation of a ciprofloxacin-resistant mutant phenotype
      via vector-driven gyrA expression was verified. Cocultivation demonstrated that
      shuttle vectors based on the pCFV108 replicon were compatible with pIP1455
      replication functions, and the stable maintenance of two plasmids in a C. fetus
      subsp. venerealis host over several months was observed. The application of both
      vector types will facilitate the investigation of the genetics and cellular
      interactions of the emerging pathogen C. fetus.

PMID- 17513581
TI  - Novel redox potential-based screening strategy for rapid isolation of Klebsiella
      pneumoniae mutants with enhanced 1,3-propanediol-producing capability.
AB  - This report describes a novel redox potential (oxidoreduction potential [ORP])
      based screening strategy for the isolation of mutants of Klebsiella pneumoniae
      which have an increased ability to produce 1,3-propanediol (1,3-PD). This method
      can be described as follows: first, to determine an ORP range which is preferred
      for the wild-type strain to grow and to produce 1,3-PD; second, to subject a
      chemically mutagenized culture to a reduced ORP level which is deleterious for
      the wild-type strain. Colonies that showed high specific growth rates at
      deleterious ORP levels were selected, and their abilities to produce 1,3-PD were
      investigated. In an ORP-based screening experiment where the ORP was controlled
      at -280 mV, 4 out of 11 isolated strains were recognized as positive mutant
      strains. A mutant which is capable of producing higher concentrations of 1,3-PD
      was subjected to fed-batch fermentations for further characterization. Its
      preferred ORP level (-280 mV) was significantly lower than that of its parent (
      190 mV). The highest 1,3-PD concentration of the mutant was 915 mmol liter(-1),
      which was 63.1% higher than that of the parent. Metabolic-flux analysis suggested
      that the intracellular reductive branch of the mutant was strengthened, which
      improved 1,3-PD biosynthesis. The procedure and results presented here provide a
      novel method of screening for strains with improved product formation.

PMID- 17513582
TI  - Alpha-agarases define a new family of glycoside hydrolases, distinct from beta
      agarase families.
AB  - The gene encoding the alpha-agarase from "Alteromonas agarilytica" (proposed
      name) has been cloned and sequenced. The gene product (154 kDa) is unrelated to
      beta-agarases and instead belongs to a new family of glycoside hydrolases (GH96).
      The alpha-agarase also displays a complex modularity, with the presence of five
      thrombospondin type 3 repeats and three carbohydrate-binding modules.

PMID- 17513583
TI  - Mutations of the Corynebacterium glutamicum NCgl1221 gene, encoding a
      mechanosensitive channel homolog, induce L-glutamic acid production.
AB  - Corynebacterium glutamicum is a biotin auxotroph that secretes L-glutamic acid in
      response to biotin limitation; this process is employed in industrial L-glutamic
      acid production. Fatty acid ester surfactants and penicillin also induce L
      glutamic acid secretion, even in the presence of biotin. However, the mechanism
      of L-glutamic acid secretion remains unclear. It was recently reported that
      disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase
      complex, resulted in L-glutamic acid secretion without induction. In this study,
      we analyzed odhA disruptants and found that those which exhibited constitutive L
      glutamic acid secretion carried additional mutations in the NCgl1221 gene, which
      encodes a mechanosensitive channel homolog. These NCgl1221 gene mutations lead to
      constitutive L-glutamic acid secretion even in the absence of odhA disruption and
      also render cells resistant to an L-glutamic acid analog, 4-fluoroglutamic acid.
      Disruption of the NCgl1221 gene essentially abolishes L-glutamic acid secretion,
      causing an increase in the intracellular L-glutamic acid pool under biotin
      limiting conditions, while amplification of the wild-type NCgl1221 gene increased
      L-glutamate secretion, although only in response to induction. These results
      suggest that the NCgl1221 gene encodes an L-glutamic acid exporter. We propose
      that treatments that induce L-glutamic acid secretion alter membrane tension and
      trigger a structural transformation of the NCgl1221 protein, enabling it to
      export L-glutamic acid.

PMID- 17513584
TI  - Molecular characterization of hsp20, encoding a small heat shock protein of
      bifidobacterium breve UCC2003.
AB  - Small heat shock proteins (sHSPs) are members of a diverse family of stress
      proteins that are important in cells to protect proteins under stressful
      conditions. Genome analysis of Bifidobacterium breve UCC2003 revealed a single
      sHSP-encoding gene, which was classified as a hsp20 gene by comparative analyses.
      Genomic surveillance of available genome sequences indicated that hsp20 homologs
      are not widely distributed in bacteria. In members of the genus Bifidobacterium,
      this gene appears to be present in only 7 of the 30 currently described species.
      Moreover, phylogenetic analysis using all available bacterial and eukaryotic sHSP
      sequences revealed a close relationship between bifidobacterial HSP20 and the
      class B sHSPs found in members of the division Firmicutes. The results of this
      comparative analysis and variation in codon usage content suggest that hsp20 was
      acquired by certain bifidobacteria through horizontal gene transfer. Analysis by
      slot blot, Northern blot, and primer extension experiments showed that
      transcription of hsp20 is strongly induced in response to severe heat shock
      regimens and by osmotic shock.

PMID- 17513585
TI  - Physiological and molecular responses of Lactuca sativa to colonization by
      Salmonella enterica serovar Dublin.
AB  - This paper describes the physiological and molecular interactions between the
      human-pathogenic organism Salmonella enterica serovar Dublin and the commercially
      available mini Roman lettuce cv. Tamburo. The association of S. enterica serovar
      Dublin with lettuce plants was first determined, which indicated the presence of
      significant populations outside and inside the plants. The latter was evidenced
      from significant residual concentrations after highly efficient surface
      disinfection (99.81%) and fluorescence microscopy of S. enterica serovar Dublin
      in cross sections of lettuce at the root-shoot transition region. The plant
      biomass was reduced significantly compared to that of noncolonized plants upon
      colonization with S. enterica serovar Dublin. In addition to the physiological
      response, transcriptome analysis by cDNA amplified fragment length polymorphism
      analysis also provided clear differential gene expression profiles between
      noncolonized and colonized lettuce plants. From these, generally and
      differentially expressed genes were selected and identified by sequence analysis,
      followed by reverse transcription-PCR displaying the specific gene expression
      profiles in time. Functional grouping of the expressed genes indicated a
      correlation between colonization of the plants and an increase in expressed
      pathogenicity-related genes. This study indicates that lettuce plants respond to
      the presence of S. enterica serovar Dublin at physiological and molecular levels,
      as shown by the reduction in growth and the concurrent expression of
      pathogenicity-related genes. In addition, it was confirmed that Salmonella spp.
      can colonize the interior of lettuce plants, thus potentially imposing a human
      health risk when processed and consumed.

PMID- 17513586
TI  - Postinoculation protozoan establishment and association patterns of methanogenic
      archaea in the ovine rumen.
AB  - Association patterns between archaea and rumen protozoa were evaluated by
      analyzing archaeal 16S rRNA gene clone libraries from ovine rumen inoculated with
      different protozoa. Five protozoan inoculation treatments, fauna free (negative
      control), holotrich and cellulolytic protozoa, Isotricha and Dasytricha spp.,
      Entodinium spp., and total fauna (type A) were tested. We used denaturing
      gradient gel electrophoresis, quantitative PCR, and phylogenetic analysis to
      evaluate the impact of the protozoan inoculants on the respective archaeal
      communities. Protozoan 18S ribosomal DNA clone libraries were also evaluated to
      monitor the protozoal population that was established by the inoculation.
      Phylogenetic analysis suggested that archaeal clones associated with the fauna
      free, the Entodinium, and the type A inoculations clustered primarily with
      uncultured phylotypes. Polyplastron multivesiculatum was the predominant
      protozoan strain established by the holotrich and cellulolytic protozoan
      treatment, and this resulted predominantly in archaeal clones affiliated with
      uncultured and cultured methanogenic phylotypes (Methanosphaera stadtmanae,
      Methanobrevibacter ruminantium, and Methanobacterium bryantii). Furthermore, the
      Isotricha and Dasytricha inoculation treatment resulted primarily in archaeal
      clones affiliated with Methanobrevibacter smithii. This report provides the first
      assessment of the influence of protozoa on archaea within the rumen microbial
      community and provides evidence to suggest that different archaeal phylotypes
      associate with specific groups of protozoa. The observed patterns may be linked
      to the evolution of commensal and symbiotic relationships between archaea and
      protozoa in the ovine rumen environment. This report further underscores the
      prevalence and potential importance of a rather large group of uncultivated
      archaea in the ovine rumen, probably unrelated to known methanogens and
      undocumented in the bovine rumen.

PMID- 17513587
TI  - Mutational analysis of endoxylanases XylA and XylB from the phytopathogen
      Fusarium graminearum reveals comprehensive insights into their inhibitor
      insensitivity.
AB  - Endo-beta-1,4-xylanases (EC 3.2.1.8; endoxylanases), key enzymes in the
      degradation of xylan, are considered to play an important role in
      phytopathogenesis, as they occupy a prominent position in the arsenal of
      hydrolytic enzymes secreted by phytopathogens to breach the cell wall and invade
      the plant tissue. Plant endoxylanase inhibitors are increasingly being pinpointed
      as part of a counterattack mechanism. To understand the surprising XIP-type
      endoxylanase inhibitor insensitivity of endoxylanases XylA and XylB from the
      phytopathogen Fusarium graminearum, an extensive mutational study of these
      enzymes was performed. Using combinatorial and site-directed mutagenesis, the XIP
      insensitivity of XylA as well as XylB was proven to be solely due to amino acid
      sequence adaptations in the "thumb" structural region. While XylB residues
      Cys141, Asp148, and Cys149 were shown to prevent XIP interaction, the XIP
      insensitivity of XylA could be ascribed to the occurrence of only one aberrant
      residue, i.e., Val151. This study, in addition to providing a thorough
      explanation for the XIP insensitivity of both F. graminearum endoxylanases at the
      molecular level, generated XylA and XylB mutants with altered inhibition
      specificities and pH optima. As this is the first experimental elucidation of the
      molecular determinants dictating the specificity of the interaction between
      endoxylanases of phytopathogenic origin and a plant inhibitor, this work sheds
      more light on the ongoing evolutionary arms race between plants and
      phytopathogenic fungi involving recognition of endoxylanases.

PMID- 17513588
TI  - Metabolic characterization of Escherichia coli strains adapted to growth on
      lactate.
AB  - In comparison with intensive studies of genetic mechanisms related to biological
      evolutionary systems, much less analysis has been conducted on metabolic network
      responses to adaptive evolution that are directly associated with evolved
      metabolic phenotypes. Metabolic mechanisms involved in laboratory evolution of
      Escherichia coli on gluconeogenic carbon sources, such as lactate, were studied
      based on intracellular flux states determined from 13C tracer experiments and 13C
      constrained flux analysis. At the end point of laboratory evolution, strains
      exhibited a more than doubling of the average growth rate and a 50% increase in
      the average biomass yield. Despite different evolutionary trajectories among
      parallel evolved populations, most improvements were obtained within the first
      250 generations of evolution and were generally characterized by a significant
      increase in pathway capacity. Partitioning between gluconeogenic and pyruvate
      catabolic flux at the pyruvate node remained almost unchanged, while flux
      distributions around the key metabolites phosphoenolpyruvate, oxaloacetate, and
      acetyl-coenzyme A were relatively flexible over the course of evolution on
      lactate to meet energetic and anabolic demands during rapid growth on this
      gluconeogenic carbon substrate. There were no clear qualitative correlations
      between most transcriptional expression and metabolic flux changes, suggesting
      complex regulatory mechanisms at multiple levels of genetics and molecular
      biology. Moreover, higher fitness gains for cell growth on both evolutionary and
      alternative carbon sources were found for strains that adaptively evolved on
      gluconeogenic carbon sources compared to those that evolved on glucose. These
      results provide a novel systematic view of the mechanisms underlying microbial
      adaptation to growth on a gluconeogenic substrate.

PMID- 17513589
TI  - Expression of reductive dehalogenase genes in Dehalococcoides ethenogenes strain
      195 growing on tetrachloroethene, trichloroethene, or 2,3-dichlorophenol.
AB  - Reductive dehalogenase (RD) gene transcript levels in Dehalococcoides ethenogenes
      strain 195 were investigated using reverse transcriptase quantitative PCR during
      growth and reductive dechlorination of tetrachloroethene (PCE), trichloroethene
      (TCE), or 2,3-dichlorophenol (2,3-DCP). Cells grown with PCE or TCE had high
      transcript levels (greater than that for rpoB) for tceA, which encodes the TCE
      RD, pceA, which encodes the PCE RD, and DET0162, which contains a predicted stop
      codon and is considered nonfunctional. In cells grown with 2,3-DCP, tceA mRNA was
      less than 1% of that for rpoB, indicating that its transcription was regulated.
      pceA and DET0162 were the only RD genes with high transcript levels in cells
      grown with 2,3-DCP. Proteomic analysis of PCE-grown cells detected both PceA and
      TceA with high peptide coverage but not DET0162, and analysis of 2,3-DCP-grown
      cells detected PceA with high coverage but not TceA, DET0162, or any other
      potential RD. Cells grown with PCE or 2,3-DCP were tested for the ability to
      dechlorinate PCE, TCE, or 2,3-DCP with H2 as the electron donor. 2,3-DCP-grown
      cells were unable to dechlorinate TCE but dechlorinated PCE to TCE without a lag,
      and PCE-grown cells dechlorinated 2,3-DCP without a lag. These results show that
      2,3-DCP-grown cells do not produce TceA and that DET0162 is transcribed but its
      translation product is not detectable in cells and are consistent with PceA's
      being bifunctional, also serving as the 2,3-DCP RD. Chlorophenols naturally occur
      in soils and are good candidates for the original substrates for PceA.

PMID- 17513590
TI  - Luciferase detection during stationary phase in Lactococcus lactis.
AB  - The luminescence signal of luxAB-encoded bacterial luciferase strongly depends on
      the metabolic state of the host cell, which restricts the use of this reporter
      system to metabolically active bacteria. Here we show that in stationary-phase
      cells of Lactococcus lactis, detection of luciferase is significantly improved by
      the addition of riboflavin or flavin mononucleotide to whole-cell assay systems.

PMID- 17513592
TI  - Extended-spectrum beta-lactamase CTX-M-1 in Escherichia coli isolates from
      healthy poultry in France.
AB  - Genes encoding extended-spectrum beta-lactamase CTX-M-1 were detected in 12
      Escherichia coli isolates recovered over a 7-month period from the ceca of
      healthy poultry in seven districts in France in 2005. Eleven of those strains
      were not clonally related and had a bla(CTX-M-1) gene located on transferable
      plasmids of different sizes and structures.

PMID- 17513593
TI  - Engineering of the yeast Yarrowia lipolytica for the production of glycoproteins
      lacking the outer-chain mannose residues of N-glycans.
AB  - In an attempt to engineer a Yarrowia lipolytica strain to produce glycoproteins
      lacking the outer-chain mannose residues of N-linked oligosaccharides, we
      investigated the functions of the OCH1 gene encoding a putative alpha-1,6
      mannosyltransferase in Y. lipolytica. The complementation of the Saccharomyces
      cerevisiae och1 mutation by the expression of YlOCH1 and the lack of in vitro
      alpha-1,6-mannosyltransferase activity in the Yloch1 null mutant indicated that
      YlOCH1 is a functional ortholog of S. cerevisiae OCH1. The oligosaccharides
      assembled on two secretory glycoproteins, the Trichoderma reesei endoglucanase I
      and the endogenous Y. lipolytica lipase, from the Yloch1 null mutant contained a
      single predominant species, the core oligosaccharide Man8GlcNAc2, whereas those
      from the wild-type strain consisted of oligosaccharides with heterogeneous sizes,
      Man8GlcNAc2 to Man12GlcNAc2. Digestion with alpha-1,2- and alpha-1,6-mannosidase
      of the oligosaccharides from the wild-type and Yloch1 mutant strains strongly
      supported the possibility that the Yloch1 mutant strain has a defect in adding
      the first alpha-1,6-linked mannose to the core oligosaccharide. Taken together,
      these results indicate that YlOCH1 plays a key role in the outer-chain
      mannosylation of N-linked oligosaccharides in Y. lipolytica. Therefore, the
      Yloch1 mutant strain can be used as a host to produce glycoproteins lacking the
      outer-chain mannoses and further developed for the production of therapeutic
      glycoproteins containing human-compatible oligosaccharides.

PMID- 17513591
TI  - Source tracking aerosols released from land-applied class B biosolids during high
      wind events.
AB  - DNA-based microbial source tracking (MST) methods were developed and used to
      specifically and sensitively track the unintended aerosolization of land-applied,
      anaerobically digested sewage sludge (biosolids) during high-wind events. Culture
      and phylogenetic analyses of bulk biosolids provided a basis for the development
      of three different MST methods. They included (i) culture- and 16S rRNA gene
      based identification of Clostridium bifermentans, (ii) direct PCR amplification
      and sequencing of the 16S rRNA gene for an uncultured bacterium of the class
      Chloroflexi that is commonly present in anaerobically digested biosolids, and
      (iii) direct PCR amplification of a 16S rRNA gene of the phylum Euryarchaeota
      coupled with terminal restriction fragment length polymorphism to distinguish
      terminal fragments that are unique to biosolid-specific microorganisms. Each
      method was first validated with a broad group of bulk biosolids and soil samples
      to confirm the target's exclusive presence in biosolids and absence in soils.
      Positive responses were observed in 100% of bulk biosolid samples and in less
      than 11% of the bulk soils tested. Next, a sampling campaign was conducted in
      which all three methods were applied to aerosol samples taken upwind and downwind
      of fields that had recently been land applied with biosolids. When average wind
      speeds were greater than 5 m/s, source tracking results confirmed the presence of
      biosolids in 56% of the downwind samples versus 3% of the upwind samples. During
      these high-wind events, the biosolid concentration in downwind aerosols was
      between 0.1 and 2 microg/m3. The application of DNA-based source tracking to
      aerosol samples has confirmed that wind is a possible mechanism for the
      aerosolization and off-site transport of land-applied biosolids.

PMID- 17513594
TI  - Diversity of nitrite reductase genes in "Candidatus Accumulibacter phosphatis"
      dominated cultures enriched by flow-cytometric sorting.
AB  - "Candidatus Accumulibacter phosphatis" is considered a polyphosphate-accumulating
      organism (PAO) though it has not been isolated yet. To reveal the denitrification
      ability of this organism, we first concentrated this organism by flow cytometric
      sorting following fluorescence in situ hybridization (FISH) using specific probes
      for this organism. The purity of the target cells was about 97% of total cell
      count in the sorted sample. The PCR amplification of the nitrite reductase genes
      (nirK and nirS) from unsorted and sorted cells was performed. Although nirK and
      nirS were amplified from unsorted cells, only nirS was detected from sorted
      cells, indicating that "Ca. Accumulibacter phosphatis" has nirS. Furthermore,
      nirS fragments were cloned from unsorted (Ba clone library) and sorted (Bd clone
      library) cells and classified by restriction fragment length polymorphism
      analysis. The most dominant clone in clone library Ba, which represented 62% of
      the total number of clones, was not found in clone library Bd. In contrast, the
      most dominant clone in clone library Bd, which represented 59% of the total
      number of clones, represented only 2% of the total number of clones in clone
      library Ba, indicating that this clone could be that of "Ca. Accumulibacter
      phosphatis." The sequence of this nirS clone exhibited less than 90% similarity
      to the sequences of known denitrifying bacteria in the database. The recovery of
      the nirS genes makes it likely that "Ca. Accumulibacter phosphatis" behaves as a
      denitrifying PAO capable of utilizing nitrite instead of oxygen as an electron
      acceptor for phosphorus uptake.

PMID- 17513595
TI  - Suitability of flow cytometry for estimating bacterial biovolume in natural
      plankton samples: comparison with microscopy data.
AB  - The relationship between flow cytometry data and epifluorescence microscopy
      measurements was assessed in bacterioplankton samples from 80 lakes to estimate
      bacterial biovolume and cell size distribution. The total counts of 4',6'
      diamidino-2-phenylindole-stained cells estimated by both methods were
      significantly related, and the slope of their linear regression was not
      significantly different from 1, indicating that both methods produce very similar
      estimates of bacterial abundance. The relationships between side scatter (SSC)
      and 4',6'-diamidino-2-phenylindole fluorescence and cell volume (microscopy
      values) were improved by binning of the data in three frequency classes for each,
      but further increases in the number of classes did not improve these
      relationships. Side scatter was the best cell volume predictor, and significant
      relationships were observed between the SSC classes and the smallest (R2 = 0.545,
      P < 0.001, n = 80) and the largest (R2 = 0.544, P < 0.001, n = 80) microscopy
      bacterial-size classes. Based on these relationships, a reliable bacterial
      biomass estimation was obtained from the SSC frequency classes. Our study
      indicates that flow cytometry can be used to properly estimate bacterioplankton
      biovolume, with an accuracy similar to those of more time-consuming microscopy
      methods.

PMID- 17513596
TI  - Rapid engineering of bacterial reporter gene fusions by using Red recombination.
AB  - Reporter gene fusions are essential tools for the investigation of gene
      regulation. Such fusions are traditionally generated by transposon mutagenesis
      and identified by a suitable selection procedure. Alternatively, specific
      reporter fusions can be generated by cloning of DNA fragments containing
      promoters or other regulatory elements in reporter plasmids. Here, we describe a
      novel approach for the rapid generation of reporter gene fusions in single copies
      at defined positions in bacterial genomes. This technique utilizes the Red
      recombinase for the homologous recombination of PCR-generated cassettes
      containing various currently used reporter genes, such as those for beta
      galactosidase, luciferase, and green fluorescent protein. The approach allows the
      generation of transcriptional or translational reporter fusions in a single step
      without the requirement for recombinant DNA constructs and is applicable to
      various enterobacterial species. Generation of reporter fusions by Red
      recombination is rapid, overcomes the current limitations of transposon
      mutagenesis or reporter plasmids, and offers new options for the study of
      bacterial gene regulation.

PMID- 17513597
TI  - Cryptococcus neoformans biofilm formation depends on surface support and carbon
      source and reduces fungal cell susceptibility to heat, cold, and UV light.
AB  - The fungus Cryptococcus neoformans possesses a polysaccharide capsule and can
      form biofilms on medical devices. We describe the characteristics of C.
      neoformans biofilm development using a microtiter plate model, microscopic
      examinations, and a colorimetric 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5
      [(phenylamino) carbonyl]-2H-tetrazolium-hydroxide (XTT) reduction assay to
      observe the metabolic activity of cryptococci within a biofilm. A strong
      correlation between XTT and CFU assays was demonstrated. Chemical analysis of the
      exopolymeric material revealed sugar composition consisting predominantly of
      xylose, mannose, and glucose, indicating the presence of other polysaccharides in
      addition to glucurunoxylomannan. Biofilm formation was affected by surface
      support differences, conditioning films on the surface, characteristics of the
      medium, and properties of the microbial cell. A specific antibody to the capsular
      polysaccharide of this fungus was used to stain the extracellular polysaccharide
      matrix of the fungal biofilms using light and confocal microscopy. Additionally,
      the susceptibility of C. neoformans biofilms and planktonic cells to
      environmental stress was investigated using XTT reduction and CFU assays.
      Biofilms were less susceptible to heat, cold, and UV light exposition than their
      planktonic counterparts. Our findings demonstrate that fungal biofilm formation
      is dependent on support surface characteristics and that growth in the biofilm
      state makes fungal cells less susceptible to potential environmental stresses.

PMID- 17513599
TI  - Inhibition of topoisomerase IIalpha and G2 cell cycle arrest by NK314, a novel
      benzo[c]phenanthridine currently in clinical trials.
AB  - NK314 is a novel synthetic benzo[c]phenanthridine alkaloid that has recently
      entered clinical trials as an antitumor compound, based on impressive activities
      in preclinical models. The present investigations were directed at determining
      the mechanism of action of this agent. NK314 induced significant G(2) cell cycle
      arrest in several cell lines, independent of p53 status, suggesting the existence
      of a common mechanism of checkpoint activation. The Chk1-Cdc25C-Cdk1 G(2)
      checkpoint pathway was activated in response to 100 nmol/L NK314 in ML-1 human
      acute myeloid leukemia cells. This was associated with the phosphorylation of the
      histone variant H2AX, an action that was predominant in the G(2) population,
      suggesting that double-strand DNA breaks caused cells to activate the checkpoint
      pathway. Double-strand DNA breaks were visualized as chromosomal aberrations when
      the G(2) checkpoint was abrogated by 7-hydroxystaurosporine. In vitro assays
      showed that NK314 inhibited the ability of topoisomerase IIalpha to relax
      supercoiled DNA and trapped topoisomerase IIalpha in its cleavage complex
      intermediate. CEM/VM1 cells, which are resistant to etoposide due to mutations in
      topoisomerase IIalpha, were cross-resistant to NK314. However, CEM/C2 cells,
      which are resistant to camptothecin due to mutations in topoisomerase I, retained
      sensitivity. These findings support the conclusion that the major mechanism of
      NK314 is to inhibit topoisomerase IIalpha, an action that leads to the generation
      of double-strand DNA breaks, which activate the G(2) DNA damage checkpoint
      pathway.

PMID- 17513600
TI  - Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro
      and in vivo.
AB  - Vascular endothelial growth factor (VEGF)-induced endothelial cell migration is
      an important component of tumor angiogenesis. Rho and Rho-associated kinase
      (ROCK) are key regulators of focal adhesion, stress fiber formation, and thus
      cell motility. Inhibitors of this pathway have been shown to inhibit endothelial
      cell motility and angiogenesis. In this study, we investigated the antiangiogenic
      effect of fasudil, one of the ROCK inhibitors. Fasudil inhibited VEGF-induced
      endothelial cell migration, viability, and tube formation in vitro in human
      umbilical vein endothelial cells. VEGF-induced endothelial cell migration was
      reduced by fasudil associated with loss of stress fiber formation, focal adhesion
      assembly, and with the suppression of tyrosine phosphorylation of focal adhesion
      proteins. Furthermore, fasudil inhibited VEGF-induced phosphorylation of myosin
      light chain, which is one of the main substrates of ROCK. Therefore, the effect
      of fasudil was suggested to be ROCK dependent. Fasudil not only inhibited VEGF
      induced cell proliferation but also reversed the protective effect of VEGF on
      apoptosis, which resulted in the decrease of cell viability. Moreover, fasudil
      inhibited VEGF-induced angiogenesis in a directed in vivo angiogenesis assay.
      These data are the first demonstration that fasudil has antiangiogenic
      properties. Therefore, fasudil might be useful for the treatment of angiogenesis
      related diseases, especially cancer.

PMID- 17513601
TI  - Classification of anti-estrogens according to intramolecular FRET effects on
      phospho-mutants of estrogen receptor alpha.
AB  - Anti-estrogen resistance is a major clinical problem in the treatment of breast
      cancer. In this study, fluorescence resonance energy transfer (FRET) analysis, a
      rapid and direct way to monitor conformational changes of estrogen receptor alpha
      (ERalpha) upon anti-estrogen binding, was used to characterize resistance to anti
      estrogens. Nine different anti-estrogens all induced a rapid FRET response within
      minutes after the compounds have liganded to ERalpha in live cells, corresponding
      to an inactive conformation of the ERalpha. Phosphorylation of Ser(305) and/or
      Ser(236) of ERalpha by protein kinase A (PKA) and of Ser(118) by mitogen
      activated protein kinase (MAPK) influenced the FRET response differently for the
      various anti-estrogens. PKA and MAPK are both associated with resistance to anti
      estrogens in breast cancer patients. Their respective actions can result in seven
      different combinations of phospho-modifications in ERalpha where the FRET effects
      of particular anti-estrogen(s) are nullified. The FRET response provided
      information on the activity of ERalpha under the various anti-estrogen conditions
      as measured in a traditional reporter assay. Tamoxifen and EM-652 were the most
      sensitive to kinase activities, whereas ICI-182,780 (Fulvestrant) and ICI-164,384
      were the most stringent. The different responses of anti-estrogens to the various
      combinations of phospho-modifications in ERalpha elucidate why certain anti
      estrogens are more prone than others to develop resistance. These data provide
      new insights into the mechanism of action of anti-hormones and are critical for
      selection of the correct individual patient-based endocrine therapy in breast
      cancer.

PMID- 17513602
TI  - Increased expression of cyclin B1 sensitizes prostate cancer cells to apoptosis
      induced by chemotherapy.
AB  - Chemotherapeutic drugs ideally should take advantage of the differences between
      transformed and normal cells and induce apoptosis only in cancer cells. One such
      difference may be the overexpression of cyclin B1 protein in cancer cells, which
      is required for the proper progression through mitosis. Previously, we showed
      that treatment of human prostate cancer cells with 2-methoxyestradiol (2-ME) or
      docetaxel results in an accumulation of cyclin B1 protein and an increase in
      cyclin B1 kinase activity, followed by induction of apoptotic cell death.
      Inhibition of cyclin B1 kinase lowers apoptosis induced by 2-ME and docetaxel. In
      this study, we established a positive correlation between cyclin B1 protein and
      apoptosis induced by chemotherapy in prostate cancer cells. There is minimal
      cyclin B1 and induction of apoptosis by chemotherapy in nontransformed cells.
      LNCaP and PC-3 prostate cancer cells stably overexpressing cyclin B1 are more
      sensitive to apoptosis induced by chemotherapy. LNCaP cells expressing cyclin B1
      small interfering RNA to lower cyclin B1 protein or dominant negative cyclin
      dependent kinase 1 to inhibit cyclin B1 kinase show a decrease in apoptosis.
      Increased sensitivity to apoptosis by overexpression of cyclin B1 may be due to
      lower Bcl-2, higher p53, and decreased neuroendocrine differentiation. We suggest
      that a cancer-specific mechanism whereby 2-ME and docetaxel may exert anti
      prostate cancer activity is the deregulated activation of cyclin B1 kinase,
      leading to the induction of apoptotic cell death. Our results also suggest that
      higher levels of cyclin B1 in prostate cancer cells may be a good prognostic
      marker for chemotherapy.

PMID- 17513603
TI  - Cellular FLICE-inhibitory protein regulates chemotherapy-induced apoptosis in
      breast cancer cells.
AB  - Combination treatment regimens that include topoisomerase-II-targeted drugs, such
      as doxorubicin, are widely used in the treatment of breast cancer. Previously, we
      showed that IFN-gamma and doxorubicin cotreatment synergistically induced
      apoptosis in MDA435 breast cancer cells in a signal transducer and activator of
      transcription 1-dependent manner. In this study, we found that this synergy was
      caspase-8 dependent. In addition, we found that IFN-gamma down-regulated the
      expression of the caspase-8 inhibitor cellular FLICE-inhibitory protein (c-FLIP).
      Furthermore, IFN-gamma down-regulated c-FLIP in a manner that was dependent on
      the transcription factors signal transducer and activator of transcription 1 and
      IFN regulatory factor-1. However, IFN-gamma had no effect on c-FLIP mRNA levels,
      indicating that c-FLIP was down-regulated at a posttranscriptional level
      following IFN-gamma treatment. Characterization of the functional significance of
      c-FLIP modulation by small interfering RNA gene silencing and stable
      overexpression studies revealed it to be a key regulator of IFN-gamma- and
      doxorubicin-induced apoptosis in MDA435 cells. Analysis of a panel of breast
      cancer cell lines indicated that c-FLIP was an important general determinant of
      doxorubicin- and IFN-gamma-induced apoptosis in breast cancer cells. Furthermore,
      c-FLIP gene silencing sensitized MDA435 cells to other chemotherapies, including
      etoposide, mitoxantrone, and SN-38. These results suggest that c-FLIP plays a
      pivotal role in modulating drug-induced apoptosis in breast cancer cells.

PMID- 17513604
TI  - Enhanced tumor cell kill by combined treatment with a small-molecule antagonist
      of mouse double minute 2 and adenoviruses encoding p53.
AB  - Strategies to treat cancer by restoring p53 tumor suppressor functions are being
      actively investigated. These approaches range from expressing an exogenous p53
      gene in p53 mutant cancers to antagonizing a p53 inhibitor in p53 wild-type (WT)
      cancer cells. In addition, exogenous p53 is used to strengthen the anticancer
      efficacy of oncolytic adenoviruses. Many cancers express high levels of the major
      negative regulator of p53, mouse double minute 2 (MDM2) protein. Recently, a
      novel class of highly potent and specific MDM2 antagonists, the Nutlins, was
      identified. We envisioned that Nutlins could protect both endogenous and
      exogenous p53 from MDM2-mediated inactivation. We therefore investigated treating
      human cancer cells with a combination of adenovirus-mediated p53 gene therapy and
      Nutlin. Combination treatment resulted in broadly effective cell kill of p53 WT
      and p53-negative cancer cells. Cytotoxicity was associated with profound cell
      cycle checkpoint activation and apoptosis induction. We also tested Nutlin in
      combination with oncolytic adenoviruses. Nutlin treatment accelerated viral
      progeny burst from oncolytic adenovirus-infected cancer cells and caused an
      estimated 10- to 1,000-fold augmented eradication of p53 WT cancer cells. These
      findings suggest that Nutlins are promising compounds to be combined with p53
      gene therapy and oncolytic virotherapy for cancer.

PMID- 17513605
TI  - 5-Aminoimidazole-4-carboxamide riboside sensitizes TRAIL- and TNF{alpha}-induced
      cytotoxicity in colon cancer cells through AMP-activated protein kinase
      signaling.
AB  - Death receptor-mediated tumor cell death, either alone or in combination with
      other anticancer drugs, is considered as a new strategy for anticancer therapy.
      In this study, we have investigated the effects and molecular mechanisms of 5
      aminoimidazole-4-carboxamide riboside [AICAR; a pharmacologic activator of AMP
      activated protein kinase (AMPK)] in sensitizing tumor necrosis factor (TNF)
      related apoptosis-inducing ligand (TRAIL)- and TNFalpha-induced apoptosis of
      human colon cancer HCT116 cells. The cytotoxic action of AICAR requires AMPK
      activation and may occur at various stages of apoptotic pathways. AICAR
      cotreatment with either TRAIL or TNFalpha enhances activities of caspase-8,
      caspase-9, and caspase-3; down-regulates the antiapoptotic protein Bcl-2;
      increases the cleavage of Bid and results in the decrease of mitochondrial
      membrane potential; potentiates activation of p38 and c-Jun NH(2)-terminal
      kinase; and inhibits nuclear factor-kappaB activity. In addition, this sensitized
      cell apoptosis was neither observed in p53-null HCT116 cells nor affected by the
      cotreatment with mevalonate. In summary, we have developed a novel strategy of
      combining AICAR with TRAIL for the treatment of colon cancer cells. The
      sensitization effect of AICAR in cell apoptosis was mediated through AMPK
      pathway, requires p53 activity, and involves mitochondria-dependent apoptotic
      cascades, p38 and c-Jun NH(2)-terminal kinase.

PMID- 17513606
TI  - A bioactive withanolide Tubocapsanolide A inhibits proliferation of human lung
      cancer cells via repressing Skp2 expression.
AB  - Withanolides are generally defined as C(28) steroidal lactones built on an intact
      or rearranged ergostane skeleton and have been shown to exhibit antiproliferative
      activity on various types of cancer cells. In this study, we investigated the
      effect of a new withanolide Tubocapsanolide A isolated from Tubocapsicum anomalum
      and addressed its molecular action. Tubocapsanolide A inhibited proliferation of
      A549, H358, and H226 human lung cancer cells via induction of G(1) growth arrest.
      We found that Tubocapsanolide A treatment led to up-regulation of cyclin E, p21,
      and p27, whereas other cyclins and cyclin-dependent kinases were not affected in
      A549 cells. Conversely, Skp2, the F-box protein that is implicated in the
      mediation of degradation of p21 and p27, was significantly down-regulated.
      Chromatin immunoprecipitation assay suggested that Tubocapsanolide A suppressed
      Skp2 expression by inhibiting the binding of Rel A to the nuclear factor-kappaB
      site of Skp2 gene promoter. In addition, we showed that inhibition of Skp2 is a
      critical step for the suppression of cell proliferation by Tubocapsanolide A
      because ectoexpression of Skp2 effectively reversed Tubocapsanolide A-induced p27
      up-regulation and growth inhibition in human lung cancer cells. Collectively, we
      have identified Skp2 as a molecular target for Tubocapsanolide A and suggest that
      this withanolide may be useful for the prevention or treatment of cancer cells
      with Skp2 overexpression.

PMID- 17513607
TI  - ZD1839 induces p15INK4b and causes G1 arrest by inhibiting the mitogen-activated
      protein kinase/extracellular signal-regulated kinase pathway.
AB  - Inactivation of the retinoblastoma protein pathway is the most common abnormality
      in malignant tumors. We therefore tried to detect agents that induce the cyclin
      dependent kinase inhibitor p15(INK4b) and found that ZD1839 (gefitinib, Iressa)
      could up-regulate p15(INK4b) expression. ZD1839 has been shown to inhibit cell
      cycle progression through inhibition of signaling pathways such as
      phosphatidylinositol 3'-kinase-Akt and mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated kinase (ERK) cascades. However, the
      mechanism responsible for the differential sensitivity of the signaling pathways
      to ZD1839 remains unclear. We here showed that ZD1839 up-regulated p15(INK4b),
      resulting in retinoblastoma hypophosphorylation and G(1) arrest in human
      immortalized keratinocyte HaCaT cells. p15(INK4b) induction was caused by
      MAPK/ERK kinase inhibitor (PD98059), but not by Akt inhibitor (SH-6, Akt-III).
      Moreover, mouse embryo fibroblasts lacking p15(INK4b) were resistant to the
      growth inhibitory effects of ZD1839 compared with wild-type mouse embryo
      fibroblasts. Additionally, the status of ERK phosphorylation was related to the
      antiproliferative activity of ZD1839 in human colon cancer HT-29 and Colo320DM
      cell lines. Our results suggest that induction of p15(INK4b) by inhibition of the
      MAPK/ERK pathway is associated with the antiproliferative effects of ZD1839.

PMID- 17513608
TI  - Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome
      proliferator-activated receptor {gamma} agonists in colon cancer cells.
AB  - Glycyrrhizin, a pentacyclic triterpene glycoside, is the major phytochemical in
      licorice. This compound and its hydrolysis product glycyrrhetinic acid have been
      associated with the multiple therapeutic properties of licorice extracts. We have
      investigated the effects of 2-cyano substituted analogues of glycyrrhetinic acid
      on their cytotoxicities and activity as selective peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists. Methyl 2-cyano-3,11-dioxo-18beta
      olean-1,12-dien-30-oate (beta-CDODA-Me) and methyl 2-cyano-3,11-dioxo-18alpha
      olean-1,12-dien-30-oate (alpha-CDODA-Me) were more cytotoxic to colon cancer
      cells than their des-cyano analogues and introduction of the 2-cyano group into
      the pentacyclic ring system was necessary for the PPARgamma agonist activity of
      alpha-CDODA-Me and beta-CDODA-Me isomers. However, in mammalian two-hybrid
      assays, both compounds differentially induced interactions of PPARgamma with
      coactivators, suggesting that these isomers, which differ only in the
      stereochemistry at C18 which affects conformation of the E-ring, are selective
      receptor modulators. This selectivity in colon cancer cells was shown for the
      induction of two proapoptotic proteins, namely caveolin-1 and the tumor
      suppressor gene Kruppel-like factor-4 (KLF-4). beta-CDODA-Me but not alpha-CDODA
      Me induced caveolin-1 in SW480 colon cancer cells, whereas caveolin-1 was induced
      by both compounds in HT-29 and HCT-15 colon cancer cells. The CDODA-Me isomers
      induced KLF-4 mRNA levels in HT-29 and SW480 cells but had minimal effects on KLF
      4 expression in HCT-15 cells. These induced responses were inhibited by
      cotreatment with a PPARgamma antagonist. This shows for the first time that
      PPARgamma agonists derived from glycyrrhetinic acid induced cell-dependent
      caveolin-1 and KLF-4 expression through receptor-dependent pathways.

PMID- 17513609
TI  - Mitochondria-mediated apoptosis by diallyl trisulfide in human prostate cancer
      cells is associated with generation of reactive oxygen species and regulated by
      Bax/Bak.
AB  - Garlic constituent diallyl trisulfide (DATS) inhibits growth of cancer cells in
      vitro and in vivo by causing apoptosis, but the sequence of events leading to
      cell death is not fully understood. We now show that DATS treatment triggers
      mitochondria-mediated apoptosis program in human prostate cancer cells (LNCaP,
      LNCaP-C81, LNCaP-C4-2) irrespective of their androgen responsiveness.
      Interestingly, a normal prostate epithelial cell line (PrEC) is significantly
      more resistant to apoptosis induction by DATS compared with prostate cancer
      cells. The DATS-induced apoptosis in LNCaP cells correlated with the collapse of
      mitochondrial membrane potential, modest increase in protein level of Bak, and
      down-regulation of Bcl-2 and Bcl-xL protein levels. The DATS-induced apoptosis
      was significantly attenuated by knockdown of Bax and Bak proteins, but not by
      ectopic expression of either Bcl-2 or Bcl-xL. The DATS treatment caused
      generation of reactive oxygen species (ROS) in LNCaP cells, but not in PrEC,
      which was attenuated by pretreatment with antioxidant N-acetylcysteine. The N
      acetylcysteine pretreatment conferred significant protection against DATS
      mediated disruption of the mitochondrial membrane potential and apoptosis. In
      conclusion, the present study reveals that the mitochondria-mediated cell death
      by DATS is associated with ROS generation and regulated by Bax/Bak but
      independent of Bcl-2 or Bcl-xL.

PMID- 17513610
TI  - Expression of human glutathione S-transferase P1 mediates the chemosensitivity of
      osteosarcoma cells.
AB  - Chemoresistance is a major reason that patients with osteosarcoma fail to achieve
      a lasting chemotherapy response, and it contributes to disease relapse,
      progression, and death. Human glutathione S-transferase P1 (GSTP1), a phase II
      detoxification enzyme, contributes to chemoresistance in many cancers. However,
      the role of GSTP1 in osteosarcoma chemoresistance is ill defined. We hypothesized
      that GSTP1 has cytoprotective effects in human osteosarcoma. To assess this
      possibility, we used GSTP1 cDNA transfection or RNA interference to overexpress
      or suppress GSTP1 in osteosarcoma cells, and assessed the cytotoxic effect of
      chemotherapeutic agents on these cells. Our results showed that GSTP1 expression
      was up-regulated in osteosarcoma cells when they were treated with doxorubicin or
      cisplatin. GSTP1 overexpression in SAOS-2 osteosarcoma cells caused the cells to
      be more resistant to doxorubicin and cisplatin. In contrast, GSTP1 suppression in
      HOS cells caused more apoptosis and extensive DNA damage in response to
      doxorubicin and cisplatin. The cytotoxicity assay also showed that GSTP1
      suppression caused a 2.5-fold increase in cell growth inhibition resulting from
      doxorubicin and cisplatin treatments [the IC(50)s are approximately 0.16
      micromol/L (doxorubicin) and 1.8 micromol/L (cisplatin) for parental HOS versus
      0.06 micromol/L (doxorubicin) and 0.75 micromol/L (cisplatin) for GSTP1-silenced
      HOS]. Moreover, GSTP1 suppression decreased the activation of extracellular
      signal-regulated kinase 1/2, which is induced by cisplatin and doxorubicin. Taken
      together, these findings show that GSTP1 contributes to doxorubicin and cisplatin
      resistance in osteosarcoma, which may be mediated in part by the activation of
      extracellular signal-regulated kinase 1/2. Targeting of GSTP1 combined with
      chemotherapy may have synergistic therapeutic effects on osteosarcoma.

PMID- 17513611
TI  - Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer
      cell lines using global gene expression profiles.
AB  - Lapatinib (GW572016) is a small-molecule dual inhibitor of epidermal growth
      factor receptor (ErbB1) and ErbB2 receptor kinase activities currently in phase
      III clinical trials. We used phosphoprotein and microarray analyses to carry out
      targeted pathway studies of phosphorylation and gene expression changes in human
      breast cancer cell lines in the presence or absence of lapatinib. Studies were
      done in four breast cancer cell lines, two of which were responsive and two of
      which were nonresponsive to lapatinib. Responsive cell lines, BT474 and SKBr3,
      constitutively overexpress ErbB2 and show an IC(50) of 25 or 32 nmol/L for
      lapatinib, respectively. In contrast, nonresponsive MDA-MB-468 and T47D cells
      expressed a low basal level of ErbB2 and showed IC(50) values in the micromolar
      range. Cells responsive to lapatinib exhibited strong differential effects on
      multiple genes in the AKT pathway. After 12 h of exposure to 1.0 micromol/L of
      lapatinib, AKT1, MAPK9, HSPCA, IRAK1, and CCND1 transcripts were down-regulated 7
      to 25-fold in responsive BT474 and SKBr3 cells. In contrast, lapatinib weakly
      down-regulated the AKT pathway in nonresponsive breast cancer cell lines (<5-fold
      down-regulation of most genes in the pathway). Furthermore, the proapoptotic gene
      FOXO3A, which is negatively regulated by AKT, was up-regulated 7- and 25-fold in
      lapatinib-responsive SKBr3 and BT474 cells, respectively. Phosphorylated Akt and
      Akt-mediated phosphorylation of FOXO3A also decreased in responsive breast cancer
      cell lines exposed to lapatinib. Gene expression profiling also revealed that
      lapatinib stimulated the expression of estrogen and progesterone receptors and
      modulated the expression of genes involved in cell cycle control, glycolysis, and
      fatty acid metabolism. In BT474 and T47D cells, which expressed moderate basal
      levels of the estrogen and progesterone receptors, 1.0 micromol/L of lapatinib
      induced expression by 7- to 11-fold. These data provide insight into the
      mechanism of action of lapatinib in breast cancer cells.

PMID- 17513612
TI  - Shikonin circumvents cancer drug resistance by induction of a necroptotic death.
AB  - Defect in apoptotic signaling and up-regulation of drug transporters in cancer
      cells significantly limits the effectiveness of cancer chemotherapy. We propose
      that an agent inducing non-apoptotic cell death may overcome cancer drug
      resistance and showed that shikonin, a naturally occurring naphthoquinone,
      induced a cell death in MCF-7 and HEK293 distinct from apoptosis and
      characterized with (a) a morphology of necrotic cell death; (b) loss of plasma
      membrane integrity; (c) loss of mitochondrial membrane potentials; (d) activation
      of autophagy as a downstream consequence of cell death, but not a contributing
      factor; (e) elevation of reactive oxygen species with no critical roles
      contributing to cell death; and (f) that the cell death was prevented by a small
      molecule, necrostatin-1, that specifically prevents cells from necroptosis. The
      characteristics fully comply with those of necroptosis, a basic cell-death
      pathway recently identified by Degterev et al. with potential relevance to human
      pathology. Furthermore, we proved that shikonin showed a similar potency toward
      drug-sensitive cancer cell lines (MCF-7 and HEK293) and their drug-resistant
      lines overexpressing P-glycoprotein, Bcl-2, or Bcl-x(L), which account for most
      of the clinical cancer drug resistance. To our best knowledge, this is the first
      report to document the induction of necroptosis by a small molecular compound to
      circumvent cancer drug resistance.

PMID- 17513613
TI  - Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma
      cells: a role for p53/activator protein 2 transcriptional regulation.
AB  - We investigated whether Rad51 overexpression plays a role in soft tissue sarcoma
      (STS) chemoresistance as well as the regulatory mechanisms underlying its
      expression. The studies reported here show that Rad51 protein is overexpressed in
      a large panel of human STS specimens. Human STS cell lines showed increased Rad51
      protein expression, as was also observed in nude rat STS xenografts. STS cells
      treated with doxorubicin exhibited up-regulation of Rad51 protein while arrested
      in the S-G(2) phase of the cell cycle. Treatment with anti-Rad51 small
      interfering RNA decreased Rad51 protein expression and increased chemosensitivity
      to doxorubicin. Because we previously showed that reintroduction of wild-type p53
      (wtp53) into STS cells harboring a p53 mutation led to increased doxorubicin
      chemosensitivity, we hypothesized that p53 participates in regulating Rad51
      expression in STS. Reintroduction of wtp53 into STS cell lines resulted in
      decreased Rad51 protein and mRNA expression. Using luciferase reporter assays, we
      showed that reconstitution of wtp53 function decreased Rad51 promoter activity.
      Deletion constructs identified a specific Rad51 promoter region containing a p53
      responsive element but no p53 consensus binding site. Electrophoretic mobility
      shift assays verified activator protein 2 (AP2) binding to this region and
      increased AP2 binding to the promoter in the presence of wtp53. Mutating this AP2
      binding site eliminated the wtp53 repressive effect. Furthermore, AP2 knockdown
      resulted in increased Rad51 expression. In light of the importance of Rad51 in
      modulating STS chemoresistance, these findings point to a potential novel
      strategy for molecular-based treatments that may be of relevance to patients
      burdened by STS.

PMID- 17513614
TI  - Transactivator of transcription-tagged cell cycle and apoptosis regulatory
      protein-1 peptides suppress the growth of human breast cancer cells in vitro and
      in vivo.
AB  - Deregulated signaling by the epidermal growth factor receptor family of proteins
      is encountered in human malignancies including breast cancer. Cell cycle and
      apoptosis-regulatory protein-1 (CARP-1), a novel, perinuclear phosphoprotein, is
      a regulator of apoptosis signaling by epidermal growth factor receptors. CARP-1
      expression is diminished in human breast cancers, and correlates inversely with
      human breast cancer grades which could be attributed to increased methylation.
      The expression of CARP-1, on the other hand, interferes with the ability of human
      breast cancer cells to invade through the matrigel-coated membranes, to form
      colonies in the soft agar, and to grow as s.c. tumors in severe combined
      immunodeficiency (SCID) mice. To test whether CARP-1 is a suppressor of human
      breast cancer growth, we generated transactivator of transcription (TAT)-tagged
      CARP-1 peptides. Treatment of human breast cancer cells with affinity purified,
      TAT-CARP-1 1-198, 197-454, and 896-1150 peptides caused inhibition of human
      breast cancer cell proliferation and elevated apoptosis. In contrast, TAT-tagged
      enhanced green fluorescent protein or CARP-1 (1-198(Y192/F)) peptide failed to
      inhibit cell proliferation or induce apoptosis. Apoptosis by CARP-1 peptides,
      with the exception of CARP-1 (1-198(Y192/F)), involves the activation of p38
      stress-activated protein kinase and caspase-9. Moreover, administration of TAT
      CARP-1 (1-198), but not TAT-tagged enhanced green fluorescent protein or TAT-CARP
      1 (1-198(Y192/F)), inhibits growth of human breast cancer cell-derived tumor
      xenografts in SCID mice. We conclude that CARP-1 is a suppressor of human breast
      cancer growth, and its expression is diminished in tumors, in part, by
      methylation-dependent silencing.

PMID- 17513615
TI  - Induction of p21 protein protects against sulforaphane-induced mitotic arrest in
      LNCaP human prostate cancer cell line.
AB  - Previous studies have indicated that d,l-sulforaphane (SFN), a synthetic cancer
      chemopreventive analogue of cruciferous vegetable-derived isomer (-)-1
      isothiocyanato-(4R)-(methylsulfinyl)-butane, activates a checkpoint kinase 2
      (Chk2)-dependent G(2)-M phase cell cycle arrest in p53-deficient human prostate
      cancer cells. Because p53 is a downstream target of Chk2 kinase and known to
      regulate G(2)-M transition by transcriptional regulation of cyclin-dependent
      kinase (Cdk) inhibitor p21(Cip1/Waf1) (p21), the present study was undertaken to
      determine the role of p21 in SFN-induced cell cycle arrest using wild-type p53
      expressing cell line LNCaP. The SFN treatment caused a modest increase in S phase
      fraction and a marked increase in G(2)-M fraction in LNCaP cells in a
      concentration- and time-dependent manner. The SFN-induced S phase arrest
      correlated with a reduction in protein levels of cyclin D1, cyclin E, Cdk4, and
      Cdk6, whereas activation of the G(2)-M checkpoint was accompanied by induction of
      cyclin B1 and down-regulation of Cdk1 and Cdc25C protein levels. The SFN-treated
      LNCaP cells were also arrested in mitosis as revealed by immunofluorescence
      microscopy and increased Ser(10) phosphorylation of histone H3, a sensitive
      marker for mitotic cells. The SFN treatment increased activating phosphorylation
      of Chk2 (Thr(68)) that was accompanied by induction of p53 and p21. The SFN
      induced mitotic arrest was statistically significantly increased by small
      interfering RNA-based knockdown of p21. However, p21 protein knockdown did not
      have any appreciable effect on SFN-induced cytoplasmic histone-associated DNA
      fragmentation (apoptosis). In conclusion, the present study indicates that
      induction of p21 protects against SFN-induced mitotic arrest in LNCaP cells.

PMID- 17513618
TI  - In one ear and out the other: communication barriers as a risk factor for
      critical incidents.

PMID- 17513616
TI  - The Src family kinase Hck regulates mast cell activation by suppressing an
      inhibitory Src family kinase Lyn.
AB  - IgE/antigen-dependent mast cell activation plays a central role in immediate
      hypersensitivity and other allergic reactions. The Src family tyrosine kinase
      (SFK) Lyn is activated by the cross-linking of high-affinity IgE receptors
      (FcepsilonRI). Activated Lyn phosphorylates the FcepsilonRI subunits, beta and
      gamma, leading to subsequent activation of various signaling pathways. Lyn also
      plays a negative regulatory function by activating negative regulatory molecules.
      Another SFK, Fyn, also contributes to mast cell degranulation by inducing Gab2
      dependent microtubule formation. Here we show that a third SFK, Hck, plays a
      critical role in mast cell activation. Degranulation and cytokine production are
      reduced in FcepsilonRI-stimulated hck(-/-) mast cells. The reduced degranulation
      can be accounted for by defects in Gab2 phosphorylation and microtubule
      formation. Importantly, Lyn activity is elevated in hck(-/-) cells, leading to
      increased phosphorylation of several negative regulators. However, positive
      regulatory events, such as activation of Syk, Btk, JNK, p38, Akt, and NF-kappaB,
      are substantially reduced in hck(-/-) mast cells. Analysis of lyn(-/-)hck(-/-),
      lyn(-/-)FcepsilonRIbeta(-/-), and hck(-/-)FcepsilonRIbeta(-/-) cells shows that
      Hck exerts these functions via both Lyn-dependent and Lyn-independent mechanisms.
      Thus, this study has revealed a hierarchical regulation among SFK members to fine
      tune mast cell activation.

PMID- 17513617
TI  - HIV modulates the expression of ligands important in triggering natural killer
      cell cytotoxic responses on infected primary T-cell blasts.
AB  - The ability of natural killer (NK) cells to kill virus-infected cells depends on
      the presence of ligands for activation receptors on the target cells. We found
      the presence of few, if any, NKp30 and NK46 ligands on T cell blasts infected
      with HIV, although NKp44 ligands were found on infected cells. HIV does induce
      the NKG2D ligands ULBP-1, -2, and -3. These ligands are involved in triggering NK
      cells to kill autologous HIV-infected cells, because interfering with the
      interaction between NKG2D, but not NKp46, on NK cells and its ligands on HIV
      infected cells drastically reduced the lysis of infected cells. Interfering with
      the binding of the NK-cell coreceptors NTB-A and 2B4 to their ligands also
      decreased destruction by NK cells. The coreceptor ligands, NTB-A and CD48, were
      also found to be down-regulated during the course of HIV infection. Thus, ligands
      for NK-cell receptors are modulated during the course of HIV infection, which may
      greatly alter NK cells' ability to kill the infected cells.

PMID- 17513619
TI  - Perioperative statin therapy: are formal guidelines and physician education
      needed?

PMID- 17513620
TI  - The impact of postoperative discontinuation or continuation of chronic statin
      therapy on cardiac outcome after major vascular surgery.
AB  - BACKGROUND: Statins reduce cardiac morbidity in nonsurgical populations, and may
      benefit surgical patients. We sought to examine cardiac outcome in patients who
      continued, compared with those who discontinued, statin therapy after major
      vascular surgery. METHODS: Prospectively collected data were examined for an
      association between statin therapy and perioperative cardiac morbidity in
      patients undergoing infrarenal aortic surgery. Between January 2001 and December
      2003, there were no guidelines for perioperative continuation of statins
      (discontinuation group, n = 491). From January 2004, guidelines were instituted
      whereby statin therapy was continued starting as soon as possible after surgery
      (continuation group, n = 178). The occurrence of cardiac myonecrosis (defined as
      an increase of cardiac troponin I more than the 99th percentile or 0.2 ng/mL) was
      analyzed. Intra-cohort (propensity score) and extra-cohort (Lee score)
      adjustments of the risk were performed. RESULTS: The median delay between surgery
      and resumption of statin therapy was 4 days and 1 day in the discontinuation and
      continuation groups (P < 0.001), respectively. Using propensity score matching
      for likelihood of preoperative treatment, the odds ratio associated with chronic
      statin treatment to predict myonecrosis for patients with versus without early
      postoperative statin resumption (continuation versus discontinuation groups) was
      0.38 and 2.1 (relative risk reduction of 5.4; 95% confidence interval: 1.2-25.3,
      P < 0.001), respectively. The odds ratio after adjustment for the Lee score was
      0.38 in the continuation group and 2.1 in the discontinuation group (relative
      reduction of 5.5; 95% confidence interval: 1.2-26.0, P < 0.001). Postoperative
      statin withdrawal (>4 days) was an independent predictor of postoperative
      myonecrosis (OR 2.9, 95% confidence interval 1.6-5.5). CONCLUSIONS:
      Discontinuation of statin therapy after major vascular surgery is associated with
      an increased postoperative cardiac risk, suggesting that statin therapy should be
      resumed early after major vascular surgery.

PMID- 17513621
TI  - The effects of morphine and fentanyl on the inflammatory response to
      cardiopulmonary bypass in patients undergoing elective coronary artery bypass
      graft surgery.
AB  - BACKGROUND: Experimental data suggest that morphine has unique antiinflammatory
      properties. We hypothesized that morphine, when compared with fentanyl, would
      attenuate the perioperative inflammatory response to cardiopulmonary bypass (CPB)
      when administered as part of a balanced anesthetic technique. METHODS: Thirty
      patients undergoing elective coronary artery bypass graft surgery were randomized
      to receive, in a double-blind manner, either morphine (40 mg) or fentanyl (1000
      microg) as part of a standardized opioid-isoflurane anesthetic. Serum
      concentrations of interleukin (IL)-6 and IL-8 and expression of neutrophil
      surface adhesion molecules (CD 11a, CD 11b, CD 11c, and CD 18) were measured
      perioperatively as indicators of the inflammatory response to surgery. Core
      temperatures were monitored in the intensive care unit to determine the incidence
      of postoperative hyperthermia (temperature >38.0 degrees C). RESULTS: IL-6 and IL
      8 concentrations increased in all patients after CPB. The increase in serum IL-6
      levels was significantly attenuated in the morphine group compared to the
      fentanyl group at 3 and 24 h post-CPB (P < 0.05). Reductions in expression of
      neutrophil adhesion molecules were observed in both groups 15 min and 3 h post
      CPB; however, a significantly larger reduction in CD 11b and CD 18 expression was
      noted in patients receiving morphine (P < 0.05). The incidence of postoperative
      hyperthermia was more frequent in the fentanyl group (73%) compared to the
      morphine group (0%, P < 0.05). CONCLUSIONS: Compared with fentanyl, the
      administration of morphine as part of balanced anesthetic technique suppressed
      several components the inflammatory response (IL-6, CD 11b, CD 18, postoperative
      hyperthermia) to cardiac surgery and CPB.

PMID- 17513622
TI  - Coagulopathy after cardiac surgery may be influenced by a functional plasminogen
      activator inhibitor polymorphism.
AB  - BACKGROUND: Cytokine-mediated inflammation and coagulopathy may occur after
      cardiac surgery. In this study we investigated the temporal pattern of
      plasminogen activator inhibitor-1 (PAI-1) gene expression after cardiac surgery
      and its relation with PAI genotype, and obtained preliminary data regarding its
      relation to perioperative morbidity. METHODS: The relative change in PAI-1 mRNA
      1, 6, and 24 h after cardiopulmonary bypass (CPB) was measured from mononuclear
      cells in 82 patients undergoing elective cardiac surgery. DNA was analyzed for
      carriage of the 4G/5G PAI-1 polymorphism. RESULTS: PAI-1 gene expression
      decreased after CPB in all patients. A larger reduction in PAI-1 gene expression
      was observed in homozygous carriers of the 5G allele. Homozygous carriers of the
      5G allele were also more likely to receive transfusion of coagulation blood
      products. There was no relation between change in PAI-1 gene expression and
      duration of CPB. CONCLUSIONS: PAI-1 gene expression decreased over time after
      CPB. We found a link between PAI-1 genotype, PAI gene expression, and transfusion
      of coagulation products after cardiac surgery.

PMID- 17513623
TI  - Transesophageal echocardiography in adult-type Bland-White-Garland syndrome.

PMID- 17513624
TI  - The "sandblasting" effect of aortic cannula on arch atheroma during
      cardiopulmonary bypass.

PMID- 17513625
TI  - The effects of jaw thrust and the lateral position on heart rate variability in
      anesthetized children with obstructive sleep apnea syndrome.
AB  - BACKGROUND: Airway obstruction occurs in anesthetized children with obstructive
      sleep apnea syndrome (OSAS). The inspiratory attempts against the occluded airway
      lead to an increased sympathetic activity. Heart rate variability (HRV) analysis
      provides information about the autonomic nervous system. The low-frequency
      component/high-frequency component ratio of HRV is considered to be an index of
      sympatho-parasympathetic balance. METHODS: We investigated the effects of general
      anesthesia, the neutral neck position, and jaw thrust in the supine and lateral
      positions on HRV in 20 children (aged 3-9 yr), with OSAS. HRV was recorded before
      and after anesthesia induction, at the neutral neck position and with jaw thrust
      maneuver in the supine and lateral positions with the patients breathing 5%
      sevoflurane. RESULTS: General anesthesia with the patient in the neutral neck
      position increased airway obstruction. The patients' stridor scores improved with
      the airway maneuver of jaw thrust and lateral position. The low-frequency
      component/high-frequency component ratio and heart rate increased at the
      postinduction measurement and reached the highest value with the patient in the
      neutral neck position. The values significantly decreased with the jaw thrust
      maneuver and with the patient in the supine and lateral positions. Ultra-short
      term entropy of HRV decreased after anesthetic induction and reached the lowest
      value with the patient in the neutral neck position. The values increased during
      jaw thrust and with patients in the supine and lateral positions. CONCLUSIONS:
      Changes of HRV induced by inhaled anesthesia, jaw thrust, and lateral positioning
      procedures corresponded to changes in the stridor score of children with OSAS.

PMID- 17513626
TI  - A comparison of single-dose caudal clonidine, morphine, or hydromorphone combined
      with ropivacaine in pediatric patients undergoing ureteral reimplantation.
AB  - BACKGROUND: Caudal blockade is a common technique for pediatric postoperative
      analgesia. While safe and effective, caudal opioids are associated with
      troublesome side effects. Caudal clonidine may offer significant analgesic
      benefits. We prospectively compared the analgesic, side effect, and
      rehabilitation profiles of caudal clonidine, hydromorphone, or morphine in a
      group of 60 pediatric patients undergoing ureteral reimplantation. METHODS:
      Patients aged 6 mo to 6 yr were evenly and randomly enrolled in a double-blind
      manner. Patients received a single caudal dose of 2 mcg/kg of clonidine, 10
      mcg/kg of hydromorphone, or 50 mcg/kg of morphine, combined with 1.0 mL/kg of
      0.2% ropivacaine with epinephrine. After sevoflurane in oxygen/air anesthesia,
      all subjects received proxy nurse-controlled analgesia with morphine.
      Postoperative pain intensity, use of IV morphine, and side effects were assessed
      during the first 24 h. Oral intake and discharge home were recorded. RESULTS:
      Caudal clonidine resulted in less postoperative nausea and vomiting (P = 0.01)
      and pruritus (P = 0.007) than did caudal hydromorphone or caudal morphine. Caudal
      morphine produced more sustained initial analgesia than did caudal clonidine (P =
      0.02). No difference was observed in pain scores, total morphine use, time to
      first oral intake or discharge home. No postoperative respiratory depression,
      excessive sedation, hypotension, or bradycardia was identified. CONCLUSIONS:
      Although caudal morphine may result in more sustained initial analgesia, caudal
      clonidine combined with nurse-controlled analgesia appears to provide comparable
      analgesia with fewer side effects. Based on these results, the use of caudal
      clonidine may be superior to caudal opioids after pediatric ureteral
      reimplantation.

PMID- 17513627
TI  - The impact of positive end-expiratory pressure on functional residual capacity
      and ventilation homogeneity impairment in anesthetized children exposed to high
      levels of inspired oxygen.
AB  - BACKGROUND: High fractions of inspired oxygen (Fio2) result in resorption
      atelectasis shortly after their application. However, the impact of different
      levels of Fio2 and their interaction with positive end-expiratory pressure (PEEP)
      on functional residual capacity (FRC) and ventilation distribution is unknown in
      anesthetized children. We hypothesized that the use of a Fio2 of 1.0 results in a
      decrease of FRC and ventilation homogeneity compared with that of a Fio2 of 0.3,
      and that this decrease is prevented by PEEP of 6-cm H2O compared to a PEEP of 3
      cm H2O. METHODS: Forty-six children (3-6 yr) without cardiopulmonary disease were
      randomly allocated to receive PEEP of 6-cm H2O (PEEP 6 group) during the entire
      study period or PEEP of 3-cm H2O (PEEP 3 group). The order of the Fio2 (0.3 or
      1.0) was also randomized. A defined recruitment maneuver was performed after
      tracheal intubation and 5 min later the first measurement. This procedure was
      then repeated with the second Fio2 level. FRC and lung clearance index (LCI) were
      calculated by a blinded observer. RESULTS: While FRC (mean +/- sd) was similar at
      both levels of Fio2 (0.3: 25.6 +/- 2.9 mL/kg vs 1.0: 25.6 +/- 2.8 mL/kg, P =
      0.189) in the PEEP 6 group, FRC decreased in the PEEP 3 group (0.3: 24.9 +/- 3.8
      vs 1.0: 21.7 +/- 4.1, P < 0.0001). Furthermore, with continuous PEEP of 6-cm H2O
      a similar LCI was observed at both levels of Fio2 (0.3: 6.45 +/- 0.4 vs 6.43 +/-
      0.4, P = 0.668) while LCI increased at the higher Fio2 in the PEEP 3 group (0.3:
      6.5 +/- 0.5 vs 1.0: 7.7 +/- 1.2, P < 0.0001). CONCLUSIONS: During the application
      of a very low PEEP of 3-cm H2O, FRC and ventilation distribution decreased
      significantly at an Fio2 of 1.0 compared with that at an Fio2 of 0.3. This
      decrease could be counterbalanced by the administration of PEEP of 6-cm H2O,
      indicating that a low level of PEEP is sufficient to maintain FRC and ventilation
      distribution regardless of the oxygen concentration.

PMID- 17513628
TI  - Granisetron versus ondansetron treatment for breakthrough postoperative nausea
      and vomiting after prophylactic ondansetron failure: a pilot study.
AB  - INTRODUCTION: Patients with an increased risk of postoperative nausea and
      vomiting (PONV) are frequently given prophylactic doses of a selective 5
      hydroxytryptamine-3 antagonist (5HT3). In chemotherapy patients, it has been
      demonstrated that after unsuccessful treatment with one 5HT3 administering a
      different 5HT3 alleviated symptoms. We hypothesized that we could define a
      benefit of a 5HT3, cross-over in a pilot study of PONV. Two-hundred-fifty female
      patients received prophylactic ondansetron 4 mg at the end of a surgical
      procedure requiring general anesthesia and were then followed postoperatively for
      4 h. METHODS: Eighty-eight women developed PONV and were randomly assigned to
      receive a repeat dose of ondansetron 4 mg (n = 30), granisetron 1 mg (n = 30), or
      granisetron 0.1 mg (n = 28) and then followed for 24 h. RESULTS: Patients
      receiving the repeat dose of ondansetron showed a complete response of 57%. Those
      receiving 1 or 0.1 mg doses of granisetron had rates of 60% and 68%,
      respectively. This difference was not statistically significant (P = 0.773).
      CONCLUSION: Unlike patients with chemotherapy-induced nausea and vomiting,
      perioperative patients who failed ondansetron prophylaxis did not have a
      significant response to cross-over dosing with granisetron.

PMID- 17513629
TI  - An evaluation of a single dose of magnesium to supplement analgesia after
      ambulatory surgery: randomized controlled trial.
AB  - BACKGROUND: Previous studies have suggested that magnesium may be a useful
      adjuvant to postoperative analgesia. METHODS: We randomized adults undergoing
      ambulatory ilioinguinal hernia repair or varicose vein operation under general
      anesthesia (propofol, fentanyl, isoflurane-N2O) to receive magnesium sulfate 4 g
      IV or physiological saline after induction. All patients preoperatively received
      diclofenac 100 mg rectally and those undergoing hernia repair had a postoperative
      ilioinguinal-iliohypogastric nerve block done. Pain, analgesic consumption, and
      adverse effects were recorded in the recovery room and, using a questionnaire, up
      to 3 days postoperatively. RESULTS: We randomized 200 patients (101 magnesium, 99
      placebo). There were no differences in hemodynamic variables before and
      immediately after study drug injection. Pain intensity at rest and on movement
      after 1, 2, and 4 h, time to first rescue analgesic, and cumulative numbers of
      non-opioid and opioid analgesics were similar among groups. There was no
      difference in the incidence of postoperative nausea and vomiting, dizziness,
      headache, or fainting. The incidence of postoperative shivering was significantly
      lower in the magnesium group (4% vs 13.1%, P = 0.0232). Adequately completed
      questionnaires were returned by 84 placebo and 82 magnesium patients. There was
      no difference between groups for any of the analyzed outcomes during the first
      three postoperative days, neither for patients undergoing inguinal hernia repair
      nor for those undergoing varicose vein stripping. CONCLUSIONS: In patients
      undergoing ambulatory ilioinguinal hernia repair or varicose vein operations
      under general anesthesia supplemented with other analgesic adjuvants,
      pretreatment with IV magnesium sulfate 4 g has no impact on postoperative pain
      and analgesic consumption.

PMID- 17513630
TI  - The role of the anesthesiologist in fast-track surgery: from multimodal analgesia
      to perioperative medical care.
AB  - BACKGROUND: Improving perioperative efficiency and throughput has become
      increasingly important in the modern practice of anesthesiology. Fast-track
      surgery represents a multidisciplinary approach to improving perioperative
      efficiency by facilitating recovery after both minor (i.e., outpatient) and major
      (inpatient) surgery procedures. In this article we focus on the expanding role of
      the anesthesiologist in fast-track surgery. METHODS: A multidisciplinary group of
      clinical investigators met at McGill University in the Fall of 2005 to discuss
      current anesthetic and surgical practices directed at improving the postoperative
      recovery process. A subgroup of the attendees at this conference was assigned the
      task of reviewing the peer-reviewed literature on this topic as it related to the
      role of the anesthesiologist as a perioperative physician. RESULTS:
      Anesthesiologists as perioperative physicians play a key role in fast-track
      surgery through their choice of preoperative medication, anesthetics and
      techniques, use of prophylactic drugs to minimize side effects (e.g., pain,
      nausea and vomiting, dizziness), as well as the administration of adjunctive
      drugs to maintain major organ system function during and after surgery.
      CONCLUSION: The decisions of the anesthesiologist as a key perioperative
      physician are of critical importance to the surgical care team in developing a
      successful fast-track surgery program.

PMID- 17513631
TI  - Modulation of remifentanil-induced postinfusion hyperalgesia by propofol.
AB  - BACKGROUND: Experimental and clinical studies suggest that brief opioid exposure
      can enhance pain sensitivity. During anesthesia, however, opioids are commonly
      administered in combination with either IV or inhaled hypnotic drugs. In this
      investigation we sought to determine the analgesic and antihyperalgesic
      properties of propofol in subhypnotic concentrations on remifentanil-induced
      postinfusion hypersensitivity in an experimental human pain model. METHODS:
      Fifteen healthy volunteers were included in this randomized, double-blind, and
      placebo-controlled study in a cross-over design. Transcutaneous electrical
      stimulation at high current densities (41.7 +/- 14.3 mA) induced spontaneous
      acute pain (numerical rating scale = 6 of 10) and stable areas of hyperalgesia.
      Pain intensities and areas of hyperalgesia were assessed before, during and after
      a 30 min target-controlled infusion of propofol (1.5 microg/mL) and remifentanil
      (0.05 microg x kg(-1) x min(-1)), either alone or in combination (propofol 1.5
      microg/mL with remifentanil 0.025 or 0.05 microg x kg(-1) x min(-1)). RESULTS:
      During infusion, propofol significantly reduced the electrically evoked pain to
      72% +/- 21% of control. Subhypnotic concentrations of propofol did not lead to
      any hyperalgesic effects. Coadministration of remifentanil led to synergistic
      analgesic effects (to 62% +/- 26% and 58% +/- 25% of control, for 0.025 or 0.05
      microg x kg(-1) x min(-1), respectively), but upon withdrawal, pain and
      hyperalgesia increased above control level. CONCLUSIONS: The results suggest
      clinically relevant interactions of propofol and remifentanil in humans, since
      propofol led to a delay and a weakening of remifentanil-induced postinfusion anti
      analgesia in humans. Nevertheless, pronociceptive effects were not completely
      antagonized by propofol, which may account for the increased demand for
      analgesics after remifentanil-based anesthesia in clinical practice.

PMID- 17513632
TI  - The effect of isoflurane, halothane and pentobarbital on noise-induced hearing
      loss in mice.
AB  - BACKGROUND: Ear surgery using mastoid drills can lead to noise-induced hearing
      loss (NIHL). We investigated whether inhaled anesthetics or pentobarbital could
      have protective effects on NIHL in mice. METHODS: Mice were exposed to broad band
      white noise for 3 h per day for 3 consecutive days, with or without anesthesia,
      using halothane, isoflurane, or pentobarbital. The hearing level of each mouse
      was analyzed before exposure, and 1 day, 1, 2, and 3 Wk, and 1 mo after noise
      exposure by measuring auditory brainstem response thresholds. At 1 Wk after noise
      exposure, the organ of Corti was stained with a fluorescent isothiocyanate
      conjugated phalloidin probe and a TUNEL kit. RESULTS: In the unanesthetized
      control group, the hearing threshold increased to 77.5 +/- 8.0 dB hearing level
      (HL) after noise stimulation. In the pentobarbital, isoflurane, and halothane
      groups, hearing threshold increased to 62.5 +/- 6.3 dB HL, 45.5 +/- 9.8 dB HL,
      and 39.3 +/- 6.2 dB HL, respectively, with all anesthetized groups of mice
      showing significantly preserved hearing compared with the control group (P <
      0.05). But, in mice anesthetized with pentobarbital, hearing loss was more severe
      than in those treated with the inhaled anesthetics (P < 0.05). Hair cell survival
      was reduced in unanesthetized control mice and somewhat reduced in pentobarbital
      treated mice, but largely unaffected in mice treated with inhaled anesthetics.
      CONCLUSIONS: These findings indicate that, while halothane, isoflurane and
      pentobarbital could protect mice against NIHL and hair cell damage, inhaled
      anesthetics were more effective.

PMID- 17513633
TI  - Morphine metabolism after major liver surgery.
AB  - BACKGROUND: Impaired metabolism of morphine may lead to an increase in sedation
      and respiratory depression. METHODS: In the present study we investigated
      morphine pharmacokinetics in patients who had undergone liver resection (n = 15)
      compared to a control group undergoing colon resection (n = 15). Morphine was
      administered IV by patient-controlled analgesia. Plasma concentrations of
      morphine, morphine-6-glucuronide, and morphine-3-glucuronide were measured 2-3
      times daily for the first two postoperative days. Pain intensity scores were
      assessed three times daily and respiratory rate and sedation scores every third
      hour. RESULTS: There were no differences in morphine requirements 1.1 (0.8-2.5
      [median, interquartile range]) mg/h (liver resection) and 1.5 (1.1-1.7) mg/h
      (colon resection) [P = 0.84]) or in pain intensity scores (P > 0.3) between the
      groups. Plasma morphine concentrations were higher in patients undergoing liver
      resection than in the control group (P < 0.01) reflecting a lower rate of
      morphine metabolism. Plasma morphine concentrations were correlated with the
      volume of liver resection (P < 0.02). However, plasma concentrations of morphine
      6-glucuronide and morphine-3-glucuronide did not differ between the groups (P =
      0.62 and P = 0.48, respectively). There was a higher incidence of sedation (P =
      0.02), but not respiratory depression (P = 0.48), after liver resection.
      CONCLUSION: The study demonstrates that plasma concentrations of morphine are
      higher in patients undergoing liver resection compared with patients undergoing
      colon resection. Sedation scores were higher in patients undergoing liver
      resection. Caution is therefore recommended when administering morphine to this
      patient group.

PMID- 17513634
TI  - Riluzole, a glutamate release inhibitor, induces loss of righting reflex,
      antinociception, and immobility in response to noxious stimulation in mice.
AB  - BACKGROUND: The general anesthetic state comprises behavioral and perceptual
      components, including amnesia, unconsciousness, analgesia, and immobility. In
      vitro, glutamatergic excitatory neurons are important targets for anesthetic
      action at the cellular and microcircuits levels. Riluzole (2-amino-6
      [trifluoromethoxy]benzothiazole) is a neuroprotective drug that inhibits
      glutamate release from nerve terminals in the central nervous system. Here, we
      examined in vivo the ability of riluzole to produce components of the general
      anesthetic state through a selective blockade of glutamatergic neurotransmission.
      METHODS: Riluzole was administered intraperitoneally in adult male ddY mice. To
      assess the general anesthetic components, three end-points were used: 1) loss of
      righting reflex (LORR; as a measure of unconsciousness), 2) loss of movement in
      response to noxious stimulation (as a measure of immobility), and 3) loss of
      nociceptive response (as a measure of analgesia). RESULTS: The intraperitoneal
      administration of riluzole induced LORR in a dose-dependent fashion with a 50%
      effective dose value of 27.4 (23.3-32.2; 95% confidence limits) mg/kg. The
      behavioral and microdialysis studies revealed that time-course changes in
      impairment and LORR induced by riluzole corresponded with decreased glutamate
      levels in the mouse brain. This suggests that riluzole-induced LORR
      (unconsciousness) could result, at least in part, from its ability to decrease
      brain glutamate concentrations. Riluzole dose-dependently produced not only LORR,
      but also loss of movement in response to painful stimulation (immobility), and
      loss of nociceptive response (analgesia) with 50% effective dose values of 43.0
      (37.1-49.9), and 10.0 (7.4-13.5) mg/kg, respectively. These three dose-response
      curves were parallel, suggesting that the behavioral effects of riluzole may be
      mediated through a common site of action. CONCLUSIONS: These findings suggest
      that riluzole-induced LORR, immobility, and antinociception appear to be
      associated with its ability to inhibit glutamatergic neurotransmission in the
      central nervous system.

PMID- 17513635
TI  - Increased gamma-aminobutyric acid levels in mouse brain induce loss of righting
      reflex, but not immobility, in response to noxious stimulation.
AB  - BACKGROUND: The general anesthetic state comprises behavioral and perceptual
      components, including amnesia, unconsciousness, and immobility. gamma
      Aminobutyric acidergic (GABAergic) inhibitory neurotransmission is an important
      target for anesthetic action at the in vitro cellular level. In vivo, however,
      the functional relevance of enhancing GABAergic neurotransmission in mediating
      essential components of the general anesthetic state is unknown. Gabaculine is a
      GABA-transaminase inhibitor that inhibits degradation of released GABA, and
      consequently increases endogenous GABA in the central nervous system. Here, we
      examined, behaviorally, the ability of increased GABA levels to produce
      components of the general anesthetic state. METHODS: All drugs were administered
      systemically in adult male ddY mice. To assess the general anesthetic components,
      two end-points were used. One was loss of righting reflex (LORR; as a measure of
      unconsciousness); the other was loss of movement in response to tail-clamp
      stimulation (as a measure of immobility). RESULTS: Gabaculine induced LORR in a
      dose-dependent fashion with a 50% effective dose of 100 (75-134; 95% confidence
      limits) mg/kg. The behavioral and microdialysis studies revealed that the
      endogenous GABA-induced LORR occurred in a brain concentration-dependent manner.
      However, even larger doses of gabaculine (285-400 mg/kg) produced no loss of tail
      clamp response. In contrast, all the tested volatile anesthetics concentration
      dependently abolished both righting and tail-clamp response, supporting the
      evidence that volatile anesthetics act on a variety of molecular targets.
      CONCLUSIONS: These findings indicate that LORR is associated with enhanced
      GABAergic neurotransmission, but that immobility in response to noxious
      stimulation is not, suggesting that LORR and immobility are mediated through
      different neuronal pathways and/or regions in the central nervous system.

PMID- 17513636
TI  - Ammonia has anesthetic properties.
AB  - BACKGROUND: A recent theory of anesthesia predicts that some endogenous compounds
      should have anesthetic properties. This theory raises the possibility that
      metabolites that are profoundly elevated in disease may also exert anesthetic
      effects. Because in pathophysiologic concentrations, ammonia reversibly impairs
      memory, consciousness, and responsiveness to noxious stimuli in a manner similar
      to anesthetics, we investigated whether ammonia had anesthetic properties.
      METHODS: The effect of ammonia was studied on alpha1beta2 and alpha1beta2gamma2s
      gamma-amino butyric acid type A, alpha1 glycine, and NR1/NR2A N-methyl-D
      aspartate receptors, and the two-pore domain potassium channel TRESK. Channels
      were expressed in Xenopus laevis oocytes and studied using two-electrode voltage
      clamping. The immobilizing effect of ammonia in rats was evaluated by determining
      the reduction in isoflurane minimum alveolar concentration produced by IV
      infusion of ammonium chloride. The olive oil-water partition coefficient was
      measured to determine whether free ammonia (NH3) followed the Meyer-Overton
      relation. RESULTS: Ammonia positively modulated TRESK channels and glycine
      receptors. No effect was seen on alpha1beta2 and alpha1beta2gamma2s gamma-amino
      butyric acid type A receptors or NR1/NR2A N-methyl-d-aspartate receptors. Ammonia
      reversibly decreased the requirement for isoflurane, with a calculated
      immobilizing EC50 of 1.6 +/- 0.1 mM NH4Cl. The Ostwald olive oil-water partition
      coefficient for NH3 was 0.018. At a pH of 7.4, and at the anesthetic EC50, the
      NH3 concentration in bulk olive oil is 0.42 muM, approximately five orders of
      magnitude less than observed by anesthetics that follow the Meyer-Overton
      relation. CONCLUSIONS: These findings support the hypothesis that ammonia has
      anesthetic properties. Bulk oil concentration did not predict the potency of
      ammonia.

PMID- 17513637
TI  - The effects of the local anesthetics lidocaine and procaine on glycine and gamma
      aminobutyric acid receptors expressed in Xenopus oocytes.
AB  - BACKGROUND: The voltage-dependent sodium channel is the primary site of action
      for local anesthetics (LAs). Although systemically administered low-dose LAs have
      been shown to exert antihyperalgesic effects, the molecular targets responsible
      for these effects are not fully known and their functional effects on inhibitory
      neurotransmitter receptors associated with antinociception have not been
      sufficiently studied. METHODS: We examined the effects of lidocaine and procaine
      (0.1 microM to 3 or 10 mM) on recombinant human alpha1 glycine,
      alpha1beta2gamma2S gamma-aminobutyric acid type A (GABA(A)), and rho1 GABA(C)
      receptors expressed in Xenopus laevis oocytes, using a two-electrode voltage
      clamp system. We also evaluated the effects of LAs on two mutant glycine
      receptors, alpha1(S267C) and alpha1(S267Q), in an effort to clarify the
      interaction between LAs and glycine receptors. RESULTS: Low concentrations of
      both lidocaine and procaine enhanced glycine receptor function, whereas high
      concentrations of lidocaine and procaine inhibited glycine receptor function.
      Lidocaine (10 microM) produced a significant leftward shift in the glycine
      concentration-response curve, indicating an increase in the apparent affinity for
      glycine. This enhancement was not altered in the mutant receptors. Both lidocaine
      and procaine at high concentrations inhibited GABA(A) receptor currents, whereas
      neither lidocaine nor procaine affected GABA(C) receptor function. CONCLUSIONS:
      Lidocaine and procaine enhanced glycine receptor function at low concentrations
      and inhibited the functions of glycine and GABA(A) receptors at high
      concentrations. The mechanism of the LA-induced enhancement of glycine receptor
      function probably differs from that of general anesthetics. These findings may
      explain the pharmacological effects of LAs, such as antinociception and
      convulsion.

PMID- 17513638
TI  - A comparison of pharmacokinetic/pharmacodynamic versus mass-balance measurement
      of brain concentrations of intravenous anesthetics in sheep.
AB  - BACKGROUND: There are two recognized methods of estimating the brain
      concentrations of IV anesthetic drugs: (i) use of pharmacokinetic/pharmacodynamic
      (PK/PD) modeling of drug effect, from arterial concentrations and
      electroencephalogram changes, and (ii) direct measurement of the uptake of drug
      in the brain, by simultaneously measuring arterial and jugular concentrations and
      cerebral blood flow (mass-balance method). These two methods have not been
      directly compared. Because an accurate estimate of the time taken for transfer of
      anesthetic drug from arterial blood to its effect-compartment in the brain is
      critical for accurate effect-compartment dosing in IV anesthesia, we compared the
      PK/PD and mass-balance methods for propofol, methohexital, and ketamine in a
      sheep model. METHODS: After instrumentation with arterial and sagittal-sinus
      cannulae, electrocorticogram, and sagittal sinus Doppler flow measurement seven
      adult sheep were given a random sequence of short anesthetic infusions with
      methohexital, ketamine, and propofol. Multiple blood samples were taken for
      measurement of the time course of the drug concentrations, and the
      electrocorticogram processed (approximate entropy, for propofol and methohexital
      and percentage high frequency time, for ketamine) to numerically quantify drug
      effect. RESULTS: Using the PK/PD method the t(1/2)K(eo) was 2.0 +/- 0.4 min for
      ketamine, 2.7 +/- 1.1 min for propofol, and was significantly shorter (0.3 +/-
      0.1 min) for methohexital. PK/PD and the mass-balance methods did not differ in
      the times to peak effect. CONCLUSIONS: Both methods of calculating the delay in
      transfer of drug from arterial blood to brain give similar values. Methohexital
      crosses into the brain much faster than either propofol or ketamine.

PMID- 17513639
TI  - Sevoflurane: are there differences in products?
AB  - Sevoflurane is currently available in the United States from two manufacturers:
      Ultane (Abbott Laboratories, Inc.) and a generic product, Sevoflurane Inhalation
      Anesthetic (Baxter Healthcare Corp.). These products are rated therapeutically
      equivalent by the Food and Drug Administration, but there are some differences.
      Ultane is made in a single-step synthetic process and generic sevoflurane is
      manufactured using a three-step process. Ultane contains >300 ppm water and
      generic sevoflurane contains < or =130 ppm water. Ultane is supplied in a plastic
      polyethylene naphthalate polymer bottle, while generic sevoflurane is supplied in
      lacquer-lined aluminum bottles. The manufacturing processes and impurities,
      sevoflurane degradation resulting from Lewis acid reactions, and suitability of
      nonglass containers for sevoflurane are discussed.

PMID- 17513640
TI  - Desflurane hepatitis associated with hapten and autoantigen-specific IgG4
      antibodies.
AB  - BACKGROUND: Three cases of drug-induced liver injury (DILI) have been reported
      after desflurane anesthesia. However, no previous reports have detected serum
      autoantibodies such as that reported with DILI from halothane or isoflurane.
      METHODS AND RESULTS: We describe the first documentation of cytochrome P450 2E1
      IgG4 autoantibodies, as well as 58 kDa endoplasmic reticulum protein and
      trifluoroacetyl chloride hapten-specific IgG4 antibodies, in a patient who
      developed DILI after desflurane anesthesia. CONCLUSIONS: These findings suggest
      that allergic and autoimmune mechanisms have critical roles in the development of
      desflurane DILI.

PMID- 17513641
TI  - An observational study of anesthesia record completeness using an anesthesia
      information management system.
AB  - BACKGROUND: Studies of the accuracy and completeness of handwritten anesthesia
      records demonstrate deficiencies in documentation, suggesting that the quality of
      anesthesia records can be improved. METHODS: We reviewed all electronic
      anesthesia records generated during a 1-month period at our institution to
      ascertain completion rates for six clinical documentation elements: allergies, IV
      access, electrocardiogram rhythm, ease of mask ventilation, laryngoscopic grade
      of view, and insertion depth of the endotracheal tube. RESULTS: Of 2838 records,
      64% had the necessary free text remark in the allergy element. The free text
      required to complete endotracheal tube depth documentation appeared in 538 of 918
      cases in which the patient was tracheally intubated (59%). Free text
      documentation of the electrocardiogram rhythm diagnosis appeared at least once in
      86% of records. Documentation of mask ventilation characteristics was entered by
      touch screen from a pick list and was expected in 781 records but appeared in 664
      records (85%). Laryngoscopic grade of view documentation was also selected by
      touch screen and expected in 883 records but present in 811 cases (92%). Any
      notation of IV access appeared in 84% of records. CONCLUSIONS: We found that
      electronic clinical anesthesia documentation was often incomplete. Dependence on
      free text remarks and the record keeping system's inability to automatically
      present entries in logical sequences consistent with workflow were associated
      with incomplete data entry. Our results suggest that the user interface for data
      entry, and the logic that an electronic system uses for preventing omissions and
      inconsistencies, merit further study and development in order to facilitate
      clinically useful documentation.

PMID- 17513642
TI  - The effect of an interactive visual reminder in an anesthesia information
      management system on timeliness of prophylactic antibiotic administration.
AB  - BACKGROUND: To reduce the incidence of surgical site infection, preoperative
      antibiotics should be administered within 60 min before surgical incision. The
      purpose of this study was to determine whether adding a visual interactive
      electronic reminder with a message related to antibiotic administration to our
      anesthesia information management system would increase compliance with
      prophylactic antibiotic guidelines. METHODS: We retrospectively studied
      electronic anesthesia records of ambulatory and day-of-surgery admission surgical
      cases in which one of our usual prophylactic antibiotics was administered from
      June 2004 through December 2005, an interval that includes cases both before and
      after the February 2005 implementation of the new reminder. Compliance was
      defined as documented antibiotic administration within 60 min before the surgical
      procedure starting time. Noncompliant cases were divided into those in which
      dosing was too early or too late. RESULTS: Compliance for 4987 cases before and
      9478 cases after the reminder was implemented increased from 82.4% to 89.1% (P <
      0.01). This increase was found both for attending anesthesiologists assisted by a
      resident or nurse anesthetist (82.9% before vs 89.1% after, P < 0.01) and for
      attending anesthesiologists working alone (80.1% before vs 89.3% after, P <
      0.01). The improvement in compliance was associated with a decrease in the
      incidence of antibiotics administered too late (i.e., after surgical incision)
      (15.2% before vs 8.1% after, P < 0.01), but with no significant change in the
      incidence of antibiotics administered too early (i.e., more than 60 min before
      skin incision) (2.4% before vs 2.8% after, P = 0.07). CONCLUSIONS: The
      implementation of a visual interactive electronic reminder regarding
      administration of preoperative antibiotics in an anesthesia information
      management system was associated with a sustained increase in compliance with
      surgical prophylactic antibiotic administration timing guidelines.

PMID- 17513643
TI  - The relationship of learning environment, quality of life, and study strategies
      measures to anesthesiology resident academic performance.
AB  - BACKGROUND: We designed this study to determine the academic performance of
      anesthesia residents as related to their differential characteristics on some
      affective-motivational variables, represented by perceptions about their
      educational environment, subjective quality of life, and learning and study
      strategies. METHODS: The study sample consisted of 63 anesthesia residents who
      completed the World Health Organization Quality of Life Inventory, the Dundee
      Ready Educational Environment Measure, the Learning and Study Strategies
      Inventory, and a progress test on basic sciences on two to four measurement
      occasions during a 2-year period. A growth curve model was fit to the academic
      performance. Mantel-Haenszel tests identified independent predictors of academic
      performance on progress tests. RESULTS: Mean rating at the first measuring
      occasion was 41%. There was a statistically significant improvement over time
      (slope = 7% per 6-m period; P < 0.01). Analysis of the random effects showed
      significant individual differences in the intercept. The residents' scores
      improved at an equivalent rate over the course of the residency. The independent
      predictors of academic performance were anxiety, motivation, and ability in
      selecting main ideas. CONCLUSIONS: Knowledge growth on basic sciences during
      anesthesia residency is significantly associated to the level of anxiety related
      to study and achievement, to the motivation for learning and for personal
      improvement, and to the ability in selecting main ideas from subject matters to
      which residents are exposed during learning episodes.

PMID- 17513644
TI  - Significant hypoglycemia secondary to icodextrin peritoneal dialysate in a
      diabetic patient.
AB  - Icodextrin, a peritoneal dialysate commonly used in the renal failure patient
      with diabetes, may lead to an overestimation of blood glucose levels as
      determined by bedside glucometers. This spurious hyperglycemia can lead to
      significant morbidity if unrecognized. We describe a case of severe hypoglycemia
      caused by an unappreciated overestimation of blood glucose in a diabetic patient
      with concomitant chronic renal failure requiring peritoneal dialysis with
      icodextrin.

PMID- 17513645
TI  - The coagulation changes induced by rapid in vivo crystalloid infusion are
      attenuated when magnesium is kept at the upper limit of normal.
AB  - BACKGROUND: Rapid crystalloid infusion enhances coagulation, regardless of
      electrolytes, pH or osmolality, an effect thought to be related to deep vein
      thrombosis and other clot formations. Altered serum magnesium may play a role in
      the balance of coagulation. In this in vivo study we investigated the coagulation
      response to rapid hemodilution when serum magnesium is maintained or partially
      increased. METHODS: Twenty-five healthy volunteers were investigated on three
      occasions, randomly receiving normal saline, Balsol (magnesium 1.5 g/L), and
      Balsol plus additional magnesium (magnesium 3.0 g/L). Investigators were blinded
      to the solution's identity. Baseline blood samples were taken measuring
      hematocrit, serum magnesium, and thrombelastography (TEG), whereafter 14 mL/kg
      (20% blood volume) was infused over 30 min, followed by a second blood sample.
      All results were compared to their own baseline values using ANOVA with LSD post
      hoc significance testing. RESULTS: All groups had a similar postdilutional
      hematocrit decrease, with significant magnesium reduction in the saline group
      (0.81 +/- 0.07 to 0.74 +/- 0.07 (approximately -8.6%) (P < 0.003)), no change in
      the Balsol group and significant increase in the Balsol + magnesium group (0.84
      +/- 0.07 to 0.99 +/- 0.06 (approximately 17.9%) (P < 0.001)). Postdilutional TEG
      results reflected no significant change from control in the Balsol + magnesium
      group. Both of the other two groups had statistically significant increased clot
      formation (reaction time to onset of clotting and clotting time shortened; alpha
      angle increased). CONCLUSIONS: Rapid hemodilution-induced coagulation may be
      partially due to decreased magnesium, and the effect is attenuated by maintaining
      magnesium at the upper limit of normal. Crystalloid resuscitation fluids should
      possibly contain higher magnesium levels, around 3 mmol/L.

PMID- 17513646
TI  - Bispectral index monitoring does not improve anesthesia performance in patients
      with movement disorders undergoing deep brain stimulating electrode implantation.
AB  - BACKGROUND: Deep brain stimulation (DBS) has emerged as a promising therapy for
      movement disorders. During the implantation procedure for the electrodes, the
      patient emerges from anesthesia repeatedly to facilitate neurological testing. We
      investigated whether Bispectral Index (BIS) monitoring would be beneficial in
      patients receiving "sleep-awake-sleep" anesthesia with respect to time of
      arousal, consumption of propofol, and cardiopulmonary stability (i.e., heart
      rate, arterial blood pressure, and end-tidal carbon dioxide). METHODS: We
      investigated 21 patients scheduled for implantation of DBS electrodes. Depth of
      propofol anesthesia was controlled either with BIS guidance in 10 patients (BIS
      group) or without in 11 patients (non-BIS group). In the BIS group, a BIS score
      of 40-60 was targeted during sleep periods, whereas in the non-BIS group, a value
      of 1 (= no response to tactile stimulation [unconsciousness]) on the Observers'
      Assessment of Alertness/Sedation Scale was targeted. For analgesia, the sites for
      the burr holes and for the pins of the stereotactic ring were infiltrated with 2%
      lidocaine; no opioids were used. For periods during which an awake patient
      required neurological testing, propofol was discontinued. RESULTS: We found no
      difference between groups with respect to times of arousal, total amount of
      propofol consumption, and cardiopulmonary stability. However, significantly more
      propofol boluses had to be administered in the BIS group (30 +/- 11.6 vs 17 +/-
      4.6) to maintain the BIS score within the target range (P < 0.05). CONCLUSION:
      BIS monitoring does not improve anesthesia management for DBS electrode
      implantation in patients with movement disorders.

PMID- 17513647
TI  - The effects of dexmedetomidine on myogenic motor evoked potentials in rabbits.
AB  - BACKGROUND: Dexmedetomidine is used in the perioperative management of patients,
      including as an intraoperative adjuvant. The effects of dexmedetomidine on
      myogenic motor evoked potentials (MEPs) remain undetermined. We conducted the
      present study to investigate the effects of dexmedetomidine on myogenic MEPs in
      rabbits. METHODS: New Zealand white rabbits were used for the studies. First, to
      determine appropriate doses of dexmedetomidine as an adjunct for anesthesia in
      rabbits, the level of anesthesia was evaluated by testing the palpebral and limb
      withdrawal reflexes, and the reactions to ear pinching and tail clamp at 5, 25,
      50, 100 microg/kg/h. Second, in 10 rabbits under ketamine and fentanyl
      anesthesia, myogenic MEPs in response to single pulse and a train-of-five pulses
      were recorded from the soleus muscle before, during, and after the administration
      of dexmedetomidine at 5, 25, and 50 microg/kg/h. RESULTS: At 50 microg/kg/h of
      dexmedetomidine, palpebral reflex, limb reflex, and reaction to ear pinching were
      inhibited in >50% of animals, but the reaction to tail clamp was not reduced.
      Dexmedetomidine suppressed myogenic MEPs in a dose-dependent manner, but when
      multipulses were used for stimulation, myogenic MEPs could be recorded in all
      animals at 50 microg/kg/h. CONCLUSIONS: As long as multipulse is used for
      stimulation, the recording of myogenic MEPs is feasible in rabbits under ketamine
      and fentanyl anesthesia during the administration of dexmedetomidine at doses
      that are an adjunct to anesthesia.

PMID- 17513648
TI  - A retrospective analysis of the effect of general anesthetics on the successful
      detection of interictal epileptiform activity in magnetoencephalography.
AB  - BACKGROUND: A magnetoencephalography (MEG) study requires the patient to lie
      still for a prolonged period of time. In children and uncooperative adults with
      epilepsy, general anesthesia or sedation may be required to insure a good quality
      study. As general anesthetics have anticonvulsant and proconvulsant properties,
      we investigated whether the use of anesthesia reduced the successful detection of
      interictal epilepsy activity. METHODS: MEG testing was performed on 41 epilepsy
      patients (10 women, 31 men; 1-48 yr) while anesthetized. To determine the impact
      of anesthesia on the identification of epileptiform activity, the anesthesia
      group of patients was compared with all other patients with epilepsy who were
      recorded in our laboratory without anesthesia, as well as with a subgroup of
      children with epilepsy who were able to be recorded without the need for
      anesthesia. RESULTS: Propofol was used in 38 patients, etomidate in two, and one
      received sevoflurane. Twenty-nine (71%) were found to have interictal
      epileptiform activity in their MEG results. The percentage of MEG studies with a
      positive yield for interictal epileptiform activity is comparable with the
      percentage (63%) found in the patients with epilepsy undergoing MEG without
      anesthesia. In the 38 children younger than 18 yr, 28 (74%) had interictal
      epileptiform activity compared with 80% done without anesthesia. CONCLUSION: We
      conclude that levels of anesthesia needed to provide unconsciousness and
      immobility during MEG studies do not significantly alter the likelihood of
      recording interictal epileptiform spike activity with MEG.

PMID- 17513649
TI  - Electrocerebral silence after intracarotid propofol injection is a function of
      transit time.
AB  - BACKGROUND: We hypothesized that the duration of electrocerebral
      (electroencephalogram, EEG) silence after bolus injection of propofol, a highly
      lipid soluble anesthetic drug, during transient cerebral hypoperfusion, will be
      directly related to the time taken by the bolus of drug to transit the cerebral
      circulation. METHODS: We randomly divided 24 New Zealand White rabbits into two
      propofol volume groups: 0.5 and 0.8 mL groups. In each group, 12 animals received
      two intracarotid injections of 1% propofol: the first injection was made under
      normal physiological conditions and the second injection during cerebral
      hypoperfusion produced by bilateral carotid occlusion and IV bolus injection of
      adenosine and esmolol. We determined the duration of electrocerebral silence and
      the transit time of propofol emulsion under both cerebral circulation conditions.
      The transit time was measured by videomicroscopy through an implanted cranial
      window. RESULTS: Cerebral hypoperfusion increased transit time with both low (2.3
      +/- 0.7 to 55.7 +/- 21.4 s, n = 12, P < 0.0001) and high (2.2 +/- 0.6 to 62.5 +/-
      31 s, n = 12, P < 0.0001) bolus volumes. The duration of electrocerebral silence
      during cerebral hypoperfusion was a function of the transit time with low
      (electrocerebral silence s = 152 + 2.3 x transit time, n = 12, r = 0.73, P =
      0.007) and high (electrocerebral silence s = 186 + 3.2 x transit time, n = 12, r
      = 0.68, P = 0.02) bolus volumes. CONCLUSION: These results suggest that
      manipulation of the transit time of highly lipid-soluble drugs profoundly
      enhances the effect site delivery.

PMID- 17513650
TI  - An assessment of the antinociceptive efficacy of intrathecal and epidural
      contulakin-G in rats and dogs.
AB  - Contulakin-G is a novel conopeptide with an incompletely defined mechanism of
      action. To assess nociceptive activity we delivered Contulakin-G as a bolus
      intrathecally (0.03, 0.1, 0.3, 3 nmol) or epidurally (10, 30, 89 nmol) in rats.
      Intrathecal Contulakin G significantly decreased Phase II and, to a lesser
      degree, Phase I paw flinching produced by intradermal formalin. Intrathecal and
      epidural doses of ED50s were 0.07 nmol and 45 nmol, respectively, giving an
      epidural/intrathecal ED50 ratio = 647). In dogs, intrathecal Contulakin-G (50-500
      nmoL) produced a dose-dependent increase in the thermally evoked skin twitch
      latency by 30 min after administration, as did morphine (150 and 450 nmol).
      Epidural morphine (750 and 7500 nmol), but not epidural 1000 nmol Contulakin-G,
      also significantly decreased skin twitch in dogs. No changes in motor function
      were seen in any rats or dogs receiving these doses of Contulakin-G. In dogs, no
      physiologically significant dose-dependent changes in motor function, heart rate,
      arterial blood pressure, or body temperature were found. Contulakin-G is a potent
      antinociceptive drug when delivered intrathecally with no observable negative
      side effects in rats or dogs and may provide an alternative to opioid spinal
      analgesics.

PMID- 17513651
TI  - The pharmacokinetics of the conopeptide contulakin-G (CGX-1160) after intrathecal
      administration: an analysis of data from studies in beagles.
AB  - BACKGROUND: The synthetic peptide agent Contulakin-G (CGX-1160), isolated from
      the toxin of the snail Conus geographus, produces significant analgesia in
      animals. Its peptide structure requires intrathecal administration for
      effectiveness, therefore we determined the intrathecal pharmacokinetics of CGX
      1160 after bolus dose and multiple day infusions to beagles. METHODS: For the
      bolus dose study, eight animals received a dose ranging from 16.7 to 1000 nmol
      under isoflurane anesthesia. Cerebral spinal fluid sampling for drug assay
      occurred up to 24 h. For the multiple day infusion study, three animals received
      infusions of 10, 40, and 160 microg/h respectively for 24 h at each rate.
      Cerebral spinal fluid sampling occurred during the infusion rate and the washout
      period after the 72 h of cumulative drug delivery. Data from the two study
      designs were modeled separately using NONMEM. RESULTS: The results showed a
      biexponential disposition profile for both experiments with a rapid rate constant
      that was an order of magnitude greater than the slow rate constant. The bolus
      results showed a nonlinear dependence of the slow rate constant on administered
      dose due to the large bolus range used in the study. CONCLUSION: These data,
      coupled with clinical pharmacology results, provide a basis for determining
      appropriate dosing strategies to achieve therapeutic intrathecal concentrations
      of Contulakin-G.

PMID- 17513652
TI  - The influence of timing of administration on the analgesic efficacy of parecoxib
      in orthopedic surgery.
AB  - BACKGROUND: Parecoxib, a selective cyclooxygenase-2 inhibitor, may reduce
      postoperative pain without increasing bleeding when administered before surgery.
      METHODS: We randomly assigned 62 patients scheduled for total hip arthroplasty to
      the following IV dosing schedule: 1) placebo at induction, at wound closure, and
      12 h after induction (control); 2) parecoxib 40 mg at induction, placebo at wound
      closure, and parecoxib 40 mg 12 h after induction (pre); or, 3) placebo at
      induction, parecoxib 40 mg at wound closure, and parecoxib 40 mg 12 h after
      induction (post). Pain scores at rest and with movement were recorded every 4 h
      for 24 h using a visual analog scale. Treatment side effects were recorded every
      4 h. Red cell loss for 5 days after surgery was calculated. RESULTS:
      Postoperative pain scores were less in the pre and post groups than in the
      control group. Postoperative bleeding was similar in the three groups. There were
      no significant differences between the pre and post groups, nor was their any
      trend suggesting a preemptive analgesic efficacy from preincision administration
      of parecoxib. Morphine use in the Postanesthesia Care Unit was reduced in the pre
      and post groups compared with the control group (14.2 +/- 2.0, and 15.7 +/- 2.0,
      vs 20.4 +/- 2.3 mg), although the trend was only significant (P < 0.05) in the
      pre group. The first pain score was also reduced in the pre and post groups
      compared to the control group (56.1 +/- 7.5 and 64.2 +/- 7.0 vs 78.3 +/- 5), but
      this was also only significant for the pre group (P = 0.001). The delay for first
      analgesic demand was increased for both the pre and post group compared to the
      control group (38 +/- 9 and 28.2 +/- 6.6 vs 18 +/- 6 min) but, again, this was
      only significant for the pre group (P = 0.05). Twenty-four hour consumption of
      morphine was similar in the pre (26 +/- 12 mg) and post groups (25 +/- 13 mg);
      both were significantly less than in the control group (47 +/- 27 mg, P < 0.001).
      CONCLUSIONS: Administration of parecoxib before hip arthroplasty did not provide
      preemptive analgesia. There was a trend towards improved analgesia immediately
      after surgery with preincision administration, consistent with the expected time
      course of nonsteroidal antiinflammatory drug's effect. Perioperative parecoxib
      administration, consisting of two injections spaced 12 h apart, improved
      postoperative analgesia over the first 24 h without increasing bleeding.

PMID- 17513653
TI  - Liposome-encapsulated ropivacaine for topical anesthesia of human oral mucosa.
AB  - BACKGROUND: The elimination of pain caused by needle insertion for local
      anesthesia would be a significant advance in dentistry. METHODS: In this blinded
      cross-over study we evaluated the efficacy of liposome-encapsulated ropivacaine
      for topical anesthesia. Thirty healthy volunteers received 60 mg topical
      anesthetics: Liposome-encapsulated 1% ropivacaine, 1% plain ropivacaine, 2.5%
      lidocaine and 2.5% prilocaine mixture (EMLA), and 20% benzocaine gel, in the
      buccal fold of the upper-right canine for 2 min in different sessions. After
      insertion of 30-G needles, pain was rated on a visual analog scale (VAS). A
      pinprick test was used to measure the duration of topical anesthesia. The pulpar
      response was assessed by an electric pulp tester. RESULTS: VAS median and
      interquartile range (in cm) were 0.8 (0.4-1.5), 1.6 (0.8-2.6), 1.1 (0.3-2.7), 2.2
      (0.9-2.9) for liposome-encapsulated ropivacaine, ropivacaine, EMLA, and
      benzocaine groups, respectively. The liposome-encapsulated ropivacaine group
      showed lower VAS mean values when compared with the benzocaine group (P =
      0.0205). The median values and interquartile range for the duration of soft
      tissue anesthesia were 11 (7-14), 6.5 (4-11), 14 (11-16), and 7 (6-9) min for
      liposome-encapsulated ropivacaine, ropivacaine, EMLA, and benzocaine groups,
      respectively. EMLA and liposome-encapsulated ropivacaine were just as efficient
      for reducing pain, and showed longer soft tissue anesthesia when compared to the
      other local anesthetics (P = 0.0001). CONCLUSION: Liposomal-encapsulated 1%
      ropivacaine gel was equivalent to EMLA for reducing pain during needle insertion
      and for the duration of soft tissue anesthesia. None of the topical anesthetics
      was effective for inducing pulpal anesthesia.

PMID- 17513654
TI  - Magnesium as an adjuvant to postoperative analgesia: a systematic review of
      randomized trials.
AB  - BACKGROUND: Randomized trials have reached different conclusions as to whether
      magnesium is a useful adjuvant to postoperative analgesia. METHODS: We performed
      a comprehensive search (electronic databases, bibliographies, all languages, to
      4.2006) for randomized comparisons of magnesium and placebo in the surgical
      setting. Information on postoperative pain intensity and analgesic requirements
      was extracted from the trials and compared qualitatively. Dichotomous data on
      adverse effects were combined using classic methods of meta-analysis. RESULTS:
      Fourteen randomized trials (778 patients, 404 received magnesium) tested
      magnesium laevulinate, gluconate or sulfate. With magnesium, postoperative pain
      intensity was significantly decreased in four (29%) trials, was no different from
      placebo in seven (50%), and was increased in one (7%); two trials (14%) did not
      report on pain intensity. With magnesium, postoperative analgesic requirements
      were significantly reduced in eight (57%) trials, were no different from placebo
      in five (36%), and were increased in one (7%). Magnesium-treated patients had
      less postoperative shivering (relative risk 0.38, 95% confidence interval 0.17
      0.88, number-needed-to-treat 14). Seven trials reported on magnesium serum
      levels. In all, serum levels were increased in patients who received magnesium;
      in six, serum levels were decreased in those who received placebo. CONCLUSIONS:
      These trials do not provide convincing evidence that perioperative magnesium may
      have favorable effects on postoperative pain intensity and analgesic
      requirements. Perioperative magnesium supplementation prevents postoperative
      hypomagnesemia and decreases the incidence of postoperative shivering. It may be
      worthwhile to further study the role of magnesium as a supplement to
      postoperative analgesia, since this relatively harmless molecule is inexpensive,
      and the biological basis for its potential antinociceptive effect is promising.

PMID- 17513655
TI  - Multimodal analgesia to prevent propofol-induced pain: pretreatment with
      remifentanil and lidocaine versus remifentanil or lidocaine alone.
AB  - BACKGROUND: Propofol is well-known for its pain on injection. Premixture with
      lidocaine or pretreatment with remifentanil reduces injection pain. A multimodal
      approach might offer additional mitigation of propofol injection pain. METHODS:
      In a randomized, prospective, double-blind study of 156 patients, we compared the
      incidence and severity of propofol pain among three groups. Patients in the
      lidocaine group (n = 54) received 2% lidocaine premixed with propofol (40 mg
      lidocaine in 180 mg propofol). Patients in the remifentanil group (n = 50),
      received pretreatment with remifentanil 2 microg x kg(-1) IV over 30 s. Patients
      in the combination group (n = 52) received both lidocaine and remifentanil.
      RESULTS: A significant decrease in the overall incidence of propofol pain at
      induction was achieved in the combination group (9.6%) compared with that in the
      remifentanil group (36%) and the lidocaine group (35%) (P = 0.003). The incidence
      of severe and moderate pain was also significantly different in the combination
      group (0%), compared with that in the remifentanil (18%) and lidocaine groups
      (12.9%) (P < 0.02). Similar, statistically significant differences among the
      three groups were achieved concerning recalled pain in the postanesthesia care
      unit. CONCLUSIONS: The combination of two different analgesic modalities,
      remifentanil and lidocaine completely abolishes moderate and severe pain
      associated with propofol injection, and significantly reduces the incidence of
      mild pain when compared with each drug used alone.

PMID- 17513657
TI  - Ten consecutive cases of complex regional pain syndrome of less than 12 months
      duration in active duty United States military personnel treated with spinal cord
      stimulation.
AB  - Complex regional pain syndrome describes a constellation of symptoms that may
      involve the sympathetic nervous system. Emerging consensus recommends early
      intervention with spinal cord stimulation to facilitate physical therapy.
      Isolated case reports suggest this may be an effective treatment. Ten consecutive
      active duty United States military personnel with newly diagnosed complex
      regional pain syndrome underwent early intervention with spinal cord stimulation
      with favorable results, including decreased pain scores and decreased opioid
      intake. Six received injuries directly as a result of service in Iraq or
      Afghanistan. These patients also had posttraumatic stress disorder, but it did
      not interfere with successful pain control. Additionally, 6 of 10 patients
      continued on active duty.

PMID- 17513656
TI  - Do surgical patients benefit from perioperative gabapentin/pregabalin? A
      systematic review of efficacy and safety.
AB  - BACKGROUND: Gabapentin and pregabalin have antiallodynic and antihyperalgesic
      properties useful for treating neuropathic pain. These properties may also be
      beneficial in acute postoperative pain. In this study we evaluated randomized,
      controlled trials examining the analgesic efficacy, adverse effects, and clinical
      value of gabapentinoids in postoperative pain. METHODS: A systematic search of
      Medline, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL)
      databases yielded 22 randomized, controlled trials on perioperative
      administration of gabapentinoids for postoperative pain relief. RESULTS: Pain
      relief was better in the gabapentin groups compared with the control groups. The
      opioid-sparing effect during the first 24 h after a single dose of gabapentin 300
      1200 mg, administered 1-2 h preoperatively, ranged from 20% to 62%. The combined
      effect of a single dose of gabapentin was a reduction of opioid consumption
      equivalent to 30 +/- 4 mg of morphine (mean +/- 95% CI) during the first 24 h
      after surgery. Metaregression analysis suggested that the gabapentin-induced
      reduction in the 24-h opioid consumption was not significantly dependent on the
      gabapentin dose. Gabapentin reduced opioid-related adverse effects, such as
      nausea, vomiting, and urinary retention (number-needed-to-treat 25, 6, and 7,
      respectively). The most common adverse effects of the gabapentinoids were
      sedation and dizziness (number-needed-to-harm 35 and 12, respectively).
      CONCLUSIONS: Gabapentinoids effectively reduce postoperative pain, opioid
      consumption, and opioid-related adverse effects after surgery. Conclusions about
      the optimal dose and duration of the treatment cannot be made because of the
      heterogeneity of the trials. Studies are needed to determine the long-term
      benefits, if any, of perioperative gabapentinoids.

PMID- 17513658
TI  - Spinal anesthesia in a patient with congenital insensitivity to pain with
      anhidrosis.
AB  - Congenital insensitivity to pain with anhidrosis (CIPA) is a rare, hereditary,
      autonomic recessive disorder. The inability to perceive pain results from loss of
      nociceptive afferents, while anhidrosis is caused by loss of innervation to the
      sweat glands. Insensitivity to pain and mental retardation lead to self-inflicted
      injuries, corneal lacerations, painless bony fractures, joint deformities with
      consequent chronic osteomyelitis, and septic arthritis. There are only a few
      reports on the anesthetic management for patients with CIPA. We describe the
      anesthetic management of a young woman with CIPA receiving bilateral arthrodesis
      of the ankle.

PMID- 17513659
TI  - The antinociceptive effects of local injections of propofol in rats are mediated
      in part by cannabinoid CB1 and CB2 receptors.
AB  - BACKGROUND: Propofol can inhibit fatty acid amidohydrolase, the enzyme
      responsible for the metabolism of anandamide (an endocannabinoid). To study the
      potential antinociceptive effect of propofol, we administered different doses
      (0.005, 0.05, 0.5, 5, and 500 microg) of the anesthetic in the hind paw of
      animals to determine an ED50. To further investigate the mechanisms by which
      propofol produced its antinociceptive effect, we used specific antagonists for
      the cannabinoid CB1 (AM251) and CB2 (AM630) receptors and measured fatty-acid
      amide/endocannabinoid (anandamide, 2-arachidonylglycerol, and
      palmitoylethanolamide) concentrations in skin paw tissues. METHODS: Formalin
      tests were performed on 65 Wistar rats allocated to six different groups: 1)
      control (Intralipidtrade mark 10%); 2) propofol (ED50 dose); 3) AM251; 4) AM251 +
      propofol; 5) AM630; 6) AM630 + propofol. Drugs were injected subcutaneously in
      the dorsal surface of the hind paw (50 microL) 15 min before 2.5% formalin
      injection into the same paw. Fatty-acid amide/endocannabinoid levels were
      measured by high performance liquid chromatography/mass spectrometry analysis.
      RESULTS: Propofol produced a dose-dependent antinociceptive effect for the early
      and late phases of the formalin test with an ED50 of 0.08 +/- 0.061 microg for
      the latter phase. This effect was antagonized by AM251 and AM630. It was locally
      mediated, since a higher dose of propofol given in the contralateral paw was not
      antinociceptive. Finally, only paw concentrations of palmitoylethanolamide were
      significantly increased. CONCLUSION: In a test of inflammatory pain, locally
      injected propofol decreased pain behavior in a dose-dependent manner. This
      antinociceptive effect was mediated, in part, by CB1 and CB2 receptors.

PMID- 17513660
TI  - Experimental neuropathy in mice is associated with delayed behavioral changes
      related to anxiety and depression.
AB  - BACKGROUND: Patients with chronic pain frequently suffer affective disorders,
      particularly anxiety and depression. Although clinical research on the
      relationship between pain and depressive symptoms has been done, it is not clear
      whether pain causes depression or depression exaggerates pain. To investigate the
      relation between pain and affect, we measured anxiety and depression-related
      behaviors in mice after spinal nerve ligation using classical behavioral tests.
      METHODS: After unilateral ligation of the left fifth lumbar nerve, we measured
      pain behaviors using von Frey and radiant heat tests. Activity level, anxiety
      related behaviors, and depression-related behaviors were tested with open field,
      light-dark exploration, elevated plus-maze, and forced swim tests. RESULTS:
      Sensory hypersensitivity was observed within a few days after ligation. Anxiety
      and depression-related behaviors were not seen 2 and 7 days after ligation.
      However, 15 and 30 days after ligation we found clear evidence of anxiety and
      depression-related behaviors, without loss of mobility. CONCLUSIONS: Nerve injury
      can trigger affective disturbances in mice that appear much later than sensory
      hypersensitivity.

PMID- 17513661
TI  - Complications and adverse effects associated with continuous peripheral nerve
      blocks in orthopedic patients.
AB  - BACKGROUND: The increasing popularity of continuous peripheral nerve blocks
      (CPNBs) warrants further study of their adverse effects and complications.
      METHODS: Anterior sciatic, femoral, and interscalene brachial plexus CPNBs were
      performed preoperatively using standardized catheter techniques in orthopedic
      patients prior to general or spinal anesthesia. Complications and adverse effects
      related to CPNBs were prospectively evaluated. RESULTS: We analyzed 1398 CPNBs in
      849 consecutive patients (mean age 65 +/- 13 yr) between 2002 and 2004. Two
      hundred-twenty-one patients received interscalene, 628 patients femoral, and 549
      sciatic CPNBs, respectively. In all the latter patients, we performed both
      femoral and sciatic CPNBs. Overall, there were 9 cases of local inflammation at
      the insertion site (0.6%), and 3 local infections (pustule) (0.2%, all femoral
      CPNBs). In one patient undergoing a femoral technique, a retroperitoneal hematoma
      led to compression injury of the femoral nerve. Complete denervation of the
      quadriceps femoris muscle was confirmed by electroneuromyography. No other major
      neurological complications were noted. There was one case of methemoglobinemia
      associated with an interscalene CPNB. Vascular puncture occurred in approximately
      6% of patients undergoing femoral and sciatic CPNBs. Catheter rupture was noted
      in one patient. CONCLUSIONS: Our results add to the evidence that major
      complications from CPNBs are rare. However, minor adverse effects associated with
      CPNBs may be more common.

PMID- 17513662
TI  - The influence of neck flexion and extension on the distribution of contrast
      medium in the high thoracic epidural space.
AB  - BACKGROUND: For safe and effective thoracic epidural analgesia (TEA), it is
      important to control the level of TEA and to identify factors that influence its
      spread. In this study, we observed the distribution of contrast injected into the
      high thoracic epidural space during neck flexion and extension. METHODS: An
      epidural catheter was inserted into the epidural space until its tip was located
      at the T1-2 intervertebral level. Patients were randomly allocated to three
      groups (extension, flexion, and neutral groups), and were injected with 5 mL of
      contrast when the neck was extended, flexed, or in the neutral position. Extent
      of contrast spread was determined by counting the number of vertebral body units
      (VBUs) through lateral epidurography. RESULTS: Forty-two patients were equally
      allocated to the three groups. Radiographic spreads in the cephalad direction
      (median) was 1.0, 5.5, and 1.5 VBUs in the extension, flexion, and neutral
      groups, and spread was greater in the flexion than in the other two groups (P <
      0.001). Median radiographic caudal spread was 10.0, 10.0, and 7.0 VBUs in the
      extension, flexion, and neutral groups, respectively, which was not significantly
      different among groups (P = 0.145). CONCLUSIONS: Cranial spread of contrast in
      the high thoracic epidural space is limited. However, neck flexion increases
      cranial spread. These results suggest that when TEA is high, the tip of the
      epidural catheter should be located at the upper part of the level to be blocked
      and that neck flexion may cause an unwanted cervical block.

PMID- 17513663
TI  - Epidural anesthesia and analgesia decrease the postoperative incidence of insulin
      resistance in preoperative insulin-resistant subjects only.
AB  - BACKGROUND: Insulin resistance (IR) is a feature of the endocrine stress response
      to surgery. It is not known whether a preoperative state of IR would affect the
      postoperative endocrine response. We sought to characterize the preoperative
      state of IR in a group of patients undergoing elective hip and knee arthroplasty,
      and to determine to what extent perioperative epidural analgesia modifies the
      postoperative state of IR in those who are and are not insulin-resistant before
      surgery. METHODS: Sixty patients undergoing either hip or knee arthroplasty were
      screened by using the homeostatic model assessment (HOMA) in two populations:
      insulin-resistant patients and noninsulin-resistant patients, whereas HOMA is
      fasting insulin (microU/mL) x fasting glucose (mmol/L)/22.5. The patients
      belonging to each population were then randomly assigned to receive either
      intraoperative epidural blockade followed by postoperative epidural analgesia
      (epidural group) or general anesthesia followed by patient-controlled analgesia
      (control group). Analgesia was assessed with visual analog scale up to 48 h after
      surgery and HOMA was repeated at the end of surgery and 48 h after surgery to
      determine the postoperative state of IR. RESULTS: Epidural anesthesia and
      analgesia significantly influenced the postoperative HOMA score (smaller
      proportion of IR) in the postoperative period only in those patients who were
      insulin-resistant before surgery (P < 0.01). In contrast, noninsulin-resistant
      patients had a similar postoperative proportion of IR between the epidural and
      control groups (P > 0.05). At rest and during movement, visual analog scale
      scores were not different between groups at the end of surgery and in the first
      and second days after surgery. CONCLUSIONS: Epidural anesthesia and analgesia
      compared to general anesthesia followed by patient-controlled analgesia decreased
      the incidence of IR soon after surgery and 48 h after surgery only in patients
      who were insulin-resistant before surgery.

PMID- 17513664
TI  - Spinal perianal block: a prospective, randomized, double-blind comparison with
      spinal saddle block.
AB  - BACKGROUND: In this prospective, randomized, double-blind study, we evaluated
      whether a very low dose of spinal bupivacaine could be sufficient for safe
      performance of short perianal surgery. METHODS: Eighty patients were randomly
      assigned to receive hyperbaric bupivacaine doses of either 1.5 mg (n = 40) or 6.0
      mg (n = 40). RESULTS: The lower dose produced satisfactory anesthesia with a more
      limited block (median S4; P < 0.01), earlier time to ambulation (98 vs 147 min; P
      < 0.01), and hospital discharge (126 vs 249 min; P < 0.01), compared with the
      higher spinal dose. CONCLUSIONS: The use of 1.5 mg spinal bupivacaine can be
      successful for short perianal surgery.

PMID- 17513665
TI  - On the hazard ratios and corresponding confidence intervals that appear in Basran
      et al. (2006).

PMID- 17513666
TI  - Fluid responsiveness assessment using the pulse oxymeter waveform: not yet ready
      for prime time.

PMID- 17513667
TI  - Variations in photoplethysmographic waveform during mechanical ventilation.

PMID- 17513668
TI  - Not all intrathecal catheter tip MRI findings are inflammatory masses.

PMID- 17513669
TI  - Let us make MRI anesthesia safe!

PMID- 17513670
TI  - Defective double lumen tubes: Mallinckrodt the culprit!

PMID- 17513671
TI  - Dynamic variables of fluid responsiveness may be related to the type of volume
      challenge performed.

PMID- 17513672
TI  - Tribulations with filling Tec 7 vaporizers.

PMID- 17513673
TI  - More than polymorphism.

PMID- 17513674
TI  - Using pulse oximetry waveform analysis to guide fluid therapy: are we there yet?

PMID- 17513675
TI  - Penetrating injury of the soft palate during GlideScope intubation.

PMID- 17513676
TI  - Reflections on motor blocking minimum local anesthetic concentrations.

PMID- 17513677
TI  - Anterior tonsillar pillar perforation during GlideScope video laryngoscopy.

PMID- 17513678
TI  - Not every hypermetabolic state is due to malignant hyperthermia!

PMID- 17513679
TI  - The sedative effect of high dose lidocaine.

PMID- 17513680
TI  - Weakness following an overdose of lidocaine during general anesthesia.

PMID- 17513681
TI  - Can electrocardiogram-controlled central line placement decrease the need for
      routine chest radiographs after central venous cannulation?

PMID- 17513682
TI  - How to enter a medication vial without coring.

PMID- 17513683
TI  - Be aware of the patient with an eye patch.

PMID- 17513684
TI  - Use of remifentanil for labor analgesia: the good and the bad.

PMID- 17513685
TI  - Transient Pourfour du Petit syndrome.

PMID- 17513686
TI  - Bispectral index does not correlate with the stress response in critical care
      patients.

PMID- 17513687
TI  - A new device for regulation of lumbar cerebrospinal fluid drainage.

PMID- 17513688
TI  - Epidemiology of lower extremity injuries among U.S. high school athletes.
AB  - OBJECTIVES: Despite the health benefits of organized sports, high school athletes
      are at risk for lower extremity sports-related injuries (LESRIs). The authors
      documented the epidemiology of LESRIs among U.S. high school athletes. METHODS:
      Via two-stage sampling, 100 U.S. high schools were randomly selected. During the
      2005 school year, LESRIs in nine sports were reported: boys' baseball, football,
      and wrestling; girls' softball and volleyball; and boys' and girls' basketball
      and soccer. The authors calculated rates as the ratio of LESRIs to the number of
      athlete exposures. National estimates were generated by assigning injuries a
      sample weight based on the inverse probability of the school's selection into the
      study. RESULTS: Among high school athletes in 2005, 2,298 of 4,350 injuries
      (52.8%) were LESRIs. This represents an estimated 807,222 LESRIs in U.S. high
      school athletes in nine sports (1.33/1,000 athlete exposures). Football had the
      highest LESRI rate for boys (2.01/1,000) and soccer the highest for girls
      (1.59/1,000). Leading diagnoses were sprains (50%), strains (17%), contusions
      (12%), and fractures (5%). The ankle (40%), knee (25%), and thigh (14%) were most
      frequently injured. Fractures occurred most often in the ankle (42%), lower leg
      (29%), or foot (18%). Girls with ligamentous knee injuries required surgery twice
      as often as boys (67% vs. 35%; p < 0.01). Girls had 1.5 times the proportion of
      season-ending LESRIs of boys (12.5% vs. 8%; p < 0.01). CONCLUSIONS: While LESRIs
      occur commonly in high school athletes, team- and gender-specific patterns exist.
      Emergency department staff will likely encounter such injuries. To optimize
      prevention strategies, ongoing surveillance is needed.

PMID- 17513689
TI  - Determination of the effect of in vitro time, temperature, and tourniquet use on
      whole blood venous point-of-care lactate concentrations.
AB  - OBJECTIVES: The authors sought to determine the effect of in vitro time,
      temperature, and removable tourniquet use on changes in venous point-of-care
      lactate concentrations. METHODS: This was a prospective randomized trial on
      healthy volunteers. Subjects were randomized to one of three groups: group 1 had
      venous lactate concentrations measured on blood drawn without a tourniquet and
      the sample placed in ice (-1 degrees C), group 2 had lactate concentrations
      measured on blood drawn without a tourniquet and the sample left at 23 degrees C,
      and group 3 had lactate concentrations measured on blood drawn with a tourniquet
      placed 5 minutes before venipuncture and the sample placed in ice (-1 degrees C).
      Lactate concentrations were measured on a point-of-care device at time 0, 3, 6,
      9, 12, and 15 minutes in all three groups. Mean lactate concentrations were
      analyzed using a two-way repeated-measures analysis of variance. RESULTS: Eighty
      subjects were randomized, with complete data available in 63 (21 per group). Over
      the 15-minute period, lactate concentrations increased 10% (0.14 +/- 0.12 mmol/L)
      in group 1, 25% (0.33 +/- 0.003 mmol/L) in group 2, and 6% (0.08 +/- 0.22 mmol/L)
      in group 3. No significant differences in mean lactate concentrations were found
      between any group or time point by analysis of variance (p > 0.90). A 50%
      relative increase in lactate concentrations between time 0 and 15 minutes
      occurred in zero of 21 subjects in group 1, four of 21 in group 2, and one of 21
      in group 3 (p = 0.05 group 1 vs. group 2, Fisher's exact test). CONCLUSIONS:
      Whole blood point-of-care lactate concentrations in healthy subjects do not
      change significantly over 15 minutes at either -1 degrees C or 23 degrees C, and
      the use of a tourniquet has no appreciable effect on lactate concentrations.

PMID- 17513690
TI  - Seeing in 3-D: examining the reach of diabetes self-management support strategies
      in a public health care system.
AB  - The authors examined whether tailored self-management support (SMS) strategies
      reach patients in a safety net system and explored variation by language,
      literacy, and insurance. English-, Spanish-, and Cantonese-speaking diabetes
      patients were randomized to weekly automated telephone disease management (ATDM)
      or monthly group medical visits. The SMS programs employ distinct communication
      methods but share common objectives, including behavioral "action plans." Reach
      was measured using three complementary dimensions: (a) participation among
      clinics, clinicians, and patients; (b) patient representativeness; and (c)
      patient engagement with SMS. Participation rates were high across all levels and
      preferentially attracted Spanish-language speakers, uninsured, and Medicaid
      recipients. Although both programs engaged a significant proportion in action
      planning, ATDM yielded higher engagement, especially among those with limited
      English proficiency and limited literacy. These results provide important
      insights for health communication and translational research with respect to
      realizing the public health benefits of SMS and can inform system-level planning
      to reduce health disparities.

PMID- 17513691
TI  - The contextual effects of gender norms, communication, and social capital on
      family planning behaviors in Uganda: a multilevel approach.
AB  - This study hypothesized a multilevel model to examine the contextual effects of
      gender norms, exposure to health-related radio programs, interpersonal
      communication, and social capital on family planning behavior in Uganda. The
      results of hierarchical linear modeling showed that all of the four variables
      were significant predictors of family planning behavior. The authors found that
      gender norms as a contextual factor significantly interacted with the individual
      level perceived benefit. The significant cross-level interaction effect was also
      observed between individuals' interpersonal communication and contextual
      variation in listening to a health-related radio program. Practical implications
      for family planning communication campaigns are discussed.

PMID- 17513693
TI  - Receptor for advanced glycation end products (RAGE) in a dash to the rescue:
      inflammatory signals gone awry in the primal response to stress.
AB  - The multiligand receptor for advanced glycation end products (RAGE) of the Ig
      superfamily transduces the biological impact of discrete families of ligands,
      including advanced glycation end products, certain members of the
      S100/calgranulin family, high mobility group box-1, Mac-1 (alpha(M)beta(2),
      CD11b/CD18), and amyloid-beta peptide and beta-sheet fibrils. Although
      structurally dissimilar, at least at the monomeric level, recent evidence
      suggests that oligomeric forms of these RAGE ligands may be especially apt to
      activate the receptor and up-regulate a program of inflammatory and tissue injury
      provoking genes. The challenge in probing the biology of RAGE and its impact in
      acute responses to stress and the potential development of chronic disease is to
      draw the line between mechanisms that evoke repair versus those that sustain
      inflammation and tissue damage. In this review, we suggest the concept that the
      ligands of RAGE comprise a primal program in the acute response to stress. When
      up-regulated in environments laden with oxidative stress, inflammation, innate
      aging, or high glucose, as examples, the function of these ligand families may be
      transformed from ones linked to rapid repair to those that drive chronic disease.
      Identification of the threshold beyond which ligands of RAGE mediate repair
      versus injury is a central component in delineating optimal strategies to target
      RAGE in the clinic.

PMID- 17513694
TI  - IL-4-stimulated NF-kappaB activity is required for Stat6 DNA binding.
AB  - IL-4 is a critical cytokine in the regulation of immune responses. In B
      lymphocytes, IL-4 signaling promotes the Stat6-dependent cell surface expression
      of several proteins including MHC Class II and CD86. However, the requirement for
      other transcription factors in IL-4-induced B cell gene expression has not been
      studied extensively. Here, we show that IL-4 induces NF-kappaB p100 processing to
      NF-kappaB p52 in B cells but not in T cells or macrophages. IL-4 induced NF
      kappaB p52 production requires PI-3K activity and correlates with IkappaB kinase
      phosphorylation and TNF receptor-associated factor 3 degradation. Blocking NF
      kappaB activity eliminates IL-4-stimulated gene expression in B cells by reducing
      IL-4-induced DNA binding but not phosphorylation or nuclear localization of
      Stat6. These results describe a novel role for NF-kappaB in IL-4-induced
      signaling and gene expression.

PMID- 17513695
TI  - The decapping activator Lsm1p-7p-Pat1p complex has the intrinsic ability to
      distinguish between oligoadenylated and polyadenylated RNAs.
AB  - Decapping is a critical step in mRNA decay. In the 5'-to-3' mRNA decay pathway
      conserved in all eukaryotes, decay is initiated by poly(A) shortening, and
      oligoadenylated mRNAs (but not polyadenylated mRNAs) are selectively decapped
      allowing their subsequent degradation by 5' to 3' exonucleolysis. The highly
      conserved heptameric Lsm1p-7p complex (made up of the seven Sm-like proteins,
      Lsm1p-Lsm7p) and its interacting partner Pat1p activate decapping by an unknown
      mechanism and localize with other decapping factors to the P-bodies in the
      cytoplasm. The Lsm1p-7p-Pat1p complex also protects the 3'-ends of mRNAs in vivo
      from trimming, presumably by binding to the 3'-ends. In order to determine the
      intrinsic RNA-binding properties of this complex, we have purified it from yeast
      and carried out in vitro analyses. Our studies revealed that it directly binds
      RNA at/near the 3'-end. Importantly, it possesses the intrinsic ability to
      distinguish between oligoadenylated and polyadenylated RNAs such that the former
      are bound with much higher affinity than the latter. These results indicate that
      the intrinsic RNA-binding characteristics of this complex form a critical
      determinant of its in vivo interactions and functions.

PMID- 17513696
TI  - Evolution of the iron-responsive element.
AB  - An RNA hairpin structure referred to as the iron-responsive element (IRE) and
      iron regulatory proteins (IRPs) are key players in the control of iron metabolism
      in animal cells. They regulate translation initiation or mRNA stability, and the
      IRE is found in a variety of mRNAs, such as those encoding ferritin, transferrin
      receptor (Tfr), erythroid aminolevulinic acid synthase (eALAS), mitochondrial
      aconitase (mACO), ferroportin, and divalent metal transporter 1 (DMT1). We have
      studied the evolution of the IRE by considering all mRNAs previously known to be
      associated with this structure and by computationally examining its occurrence in
      a large variety of eukaryotic organisms. More than 100 novel sequences together
      with approximately 50 IREs that were previously reported resulted in a
      comprehensive view of the phylogenetic distribution of this element. A comparison
      of the different mRNAs shows that the IREs of eALAS and mACO are found in
      chordates, those of ferroportin and Tfr1 are found in vertebrates, and the IRE of
      DMT1 is confined to mammals. In contrast, the IRE of ferritin occurs in a
      majority of metazoa including lower metazoa such as sponges and Nematostella (sea
      anemone). These findings suggest that the ferritin IRE represents the ancestral
      version of this type of translational control and that during the evolution of
      higher animals the IRE structure was adopted by other genes. On the basis of
      primary sequence comparison between different organisms, we suggest that some of
      these IREs developed by "convergent evolution" through stepwise changes in
      sequence, rather than by recombination events.

PMID- 17513698
TI  - Multiple variants in vascular endothelial growth factor (VEGFA) are risk factors
      for time to severe retinopathy in type 1 diabetes: the DCCT/EDIC genetics study.
AB  - OBJECTIVE: We sought to determine if any common variants in the gene for vascular
      endothelial growth factor (VEGFA) are associated with long-term renal and retinal
      complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 1,369
      Caucasian subjects with type 1 diabetes from the Diabetes Control and
      Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and
      Complications (EDIC) Study had an average of 17 retinal photographs and 10 renal
      measures over 15 years. In the DCCT/EDIC, we studied 18 single nucleotide
      polymorphisms (SNPs) in VEGFA that represent all linkage disequilibrium bins
      (pairwise r(2) > or = 0.64) and tested them for association with time to
      development of severe retinopathy, three or more step progression of retinopathy,
      clinically significant macular edema, persistent microalbuminuria, and severe
      nephropathy. RESULTS: In a global multi-SNP test, there was a highly significant
      association of VEGFA SNPs with severe retinopathy (P = 6.8 x 10(-5))-the four
      other outcomes were all nonsignificant. In survival analyses controlling for
      covariate risk factors, eight SNPs showed significant association with severe
      retinopathy (P < 0.05). The most significant single SNP association was rs3025021
      (hazard ratio 1.37 [95% CI 1.13-1.66], P = 0.0017). Family-based analyses of
      severe retinopathy provide evidence of excess transmission of C at rs699947 (P =
      0.029), T at rs3025021 (P = 0.013), and the C-T haplotype from both SNPs (P =
      0.035). Multi-SNP regression analysis including 15 SNPs, and allowing for
      pairwise interactions, independently selected 6 significant SNPs (P < 0.05).
      CONCLUSIONS: These data demonstrate that multiple VEGFA variants are associated
      with the development of severe retinopathy in type 1 diabetes.

PMID- 17513697
TI  - The NS3 protein of Rice hoja blanca tenuivirus suppresses RNA silencing in plant
      and insect hosts by efficiently binding both siRNAs and miRNAs.
AB  - RNA silencing plays a key role in antiviral defense as well as in developmental
      processes in plants and insects. Negative strand RNA viruses such as the plant
      virus Rice hoja blanca tenuivirus (RHBV) replicate in plants and in their insect
      transmission vector. Like most plant-infecting viruses, RHBV encodes an RNA
      silencing suppressor, the NS3 protein, and here it is demonstrated that this
      protein is capable of suppressing RNA silencing in both plants and insect cells.
      Biochemical analyses showed that NS3 efficiently binds siRNA as well as miRNA
      molecules. Binding of NS3 is greatly influenced by the size of small RNA
      molecules, as 21 nucleotide (nt) siRNA molecules are bound > 100 times more
      efficiently than 26 nt species. Competition assays suggest that the activity of
      NS3 is based on binding to siRNAs prior to strand separation during the assembly
      of the RNA-induced silencing complex. In addition, NS3 has a high affinity for
      miRNA/miRNA* duplexes, indicating that its activity might also interfere with
      miRNA-regulated gene expression in both insects and plants.

PMID- 17513699
TI  - Skeletal muscle adaptation to exercise training: AMP-activated protein kinase
      mediates muscle fiber type shift.
AB  - Regular endurance exercise has profound benefits on overall health, including the
      prevention of obesity, cardiovascular disease, and diabetes. The objective of
      this study was to determine whether AMP-activated protein kinase (AMPK) mediates
      commonly observed adaptive responses to exercise training in skeletal muscle. Six
      weeks of voluntary wheel running induced a significant (P < 0.05) fiber type IIb
      to IIa/x shift in triceps muscle of wild-type mice. Despite similar wheel running
      capacities, this training-induced shift was reduced by approximately 40% in
      transgenic mice expressing a muscle-specific AMPKalpha2 inactive subunit.
      Sedentary mice carrying an AMPK-activating mutation (gamma1TG) showed a 2.6-fold
      increase in type IIa/x fibers but no further increase with training. To determine
      whether AMPK is involved in concomitant metabolic adaptations to training, we
      measured markers of mitochondria (citrate synthase and succinate dehydrogenase)
      and glucose uptake capacity (GLUT4 and hexokinase II). Mitochondrial markers
      increased similarly in wild-type and AMPKalpha2-inactive mice. Sedentary gamma1TG
      mice showed a approximately 25% increase in citrate synthase activity but no
      further increase with training. GLUT4 protein expression was not different in
      either line of transgenic mice compared with wild-type mice and tended to
      increase with training, although this increase was not statistically significant.
      Training induced a approximately 65% increase in hexokinase II protein in wild
      type mice but not in AMPKalpha2-inactive mice. Hexokinase II was significantly
      elevated in sedentary gamma1TG mice, without an additional increase with
      training. AMPK is not necessary for exercise training-induced increases in
      mitochondrial markers, but it is essential for fiber type IIb to IIa/x
      transformation and increases in hexokinase II protein.

PMID- 17513700
TI  - Selective downregulation of the high molecular weight form of adiponectin in
      hyperinsulinemia and in type 2 diabetes: differential regulation from nondiabetic
      subjects.
AB  - OBJECTIVE: Adiponectin is an adipocyte-specific secretory protein found in
      circulation in several different forms and is present at significantly lower
      levels in the plasma of diabetic patients compared with that of insulin-sensitive
      individuals. We wanted to test whether insulin per se is a contributing factor
      toward lower plasma adiponectin concentrations and, if so, whether the splanchnic
      bed contributes to this phenomenon. RESEARCH DESIGN AND METHODS: We sampled
      femoral artery and hepatic venous samples and measured the high-molecular weight
      (HMW) and low-molecular weight (LMW) fractions of adiponectin in 11 type 2
      diabetic and 7 nondiabetic subjects matched for age, sex, and BMI during basal
      conditions and during a hyperglycemic (approximately 9.5 mmol/l) hyperinsulinemic
      (approximately 700 pmol/l) clamp. RESULTS: Under these conditions, total arterial
      adiponectin, HMW, and the ratio of HMW to total adiponectin all were lower (P <
      0.01) in the diabetic versus nondiabetic subjects, whereas the LMW form did not
      significantly differ. Under hyperinsulinemic conditions, total adiponectin levels
      dropped, primarily due to a reduction of the HMW form, whereas LMW forms were not
      significantly affected. CONCLUSIONS: HMW adiponectin and the ratio of HMW to
      total adiponectin are lower in individuals with diabetes than in nondiabetic
      subjects. We conclude that HMW adiponectin is downregulated in hyperinsulinemia
      and type 2 diabetes.

PMID- 17513701
TI  - Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic
      state?
AB  - We aimed to investigate whether the reduced incretin effect observed in patients
      with type 2 diabetes is a primary event in the pathogenesis of type 2 diabetes or
      a consequence of the diabetic state. Eight patients with chronic pancreatitis and
      secondary diabetes (A1C mean [range] of 6.9% [6.2-8.0]), eight patients with
      chronic pancreatitis and normal glucose tolerance (NGT; 5.3 [4.9-5.7]), eight
      patients with type 2 diabetes (6.9 [6.2-8.0]); and eight healthy subjects (5.5
      [5.1-5.8]) were studied. Blood was sampled over 4 h on 2 separate days after a 50
      g oral glucose load and an isoglycemic intravenous glucose infusion,
      respectively. The incretin effect (100% x [beta-cell secretory response to oral
      glucose tolerance test - intravenous beta-cell secretory response]/beta-cell
      secretory response to oral glucose tolerance test) was significantly (P < 0.05)
      reduced (means +/- SE) in patients with chronic pancreatitis and secondary
      diabetes (31 +/- 4%) compared with patients with chronic pancreatitis and NGT (68
      +/- 3) and healthy subjects (60 +/- 4), respectively. In the type 2 diabetes
      group, the incretin effect amounted to 36 +/- 6%, significantly (P < 0.05) lower
      than in chronic pancreatitis patients with NGT and in healthy subjects,
      respectively. These results suggest that the reduced incretin effect is not a
      primary event in the development of type 2 diabetes, but rather a consequence of
      the diabetic state.

PMID- 17513702
TI  - Effects of endurance exercise training on insulin signaling in human skeletal
      muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and
      AS160.
AB  - The purpose of this study was to investigate the mechanisms explaining improved
      insulin-stimulated glucose uptake after exercise training in human skeletal
      muscle. Eight healthy men performed 3 weeks of one-legged knee extensor endurance
      exercise training. Fifteen hours after the last exercise bout, insulin-stimulated
      glucose uptake was approximately 60% higher (P < 0.01) in the trained compared
      with the untrained leg during a hyperinsulinemic-euglycemic clamp. Muscle
      biopsies were obtained before and after training as well as after 10 and 120 min
      of insulin stimulation in both legs. Protein content of Akt1/2 (55 +/- 17%, P <
      0.05), AS160 (25 +/- 8%, P = 0.08), GLUT4 (52 +/- 19%, P < 0.001), hexokinase 2
      (HK2) (197 +/- 40%, P < 0.001), and insulin-responsive aminopeptidase (65 +/-
      15%, P < 0.001) increased in muscle in response to training. During
      hyperinsulinemia, activities of insulin receptor substrate-1 (IRS-1)-associated
      phosphatidylinositol 3-kinase (PI3-K) (P < 0.005), Akt1 (P < 0.05), Akt2 (P <
      0.005), and glycogen synthase (GS) (percent I-form, P < 0.05) increased similarly
      in both trained and untrained muscle, consistent with increased phosphorylation
      of Akt Thr(308), Akt Ser(473), AS160, glycogen synthase kinase (GSK)-3alpha
      Ser(21), and GSK-3beta Ser(9) and decreased phosphorylation of GS site 3a+b (all
      P < 0.005). Interestingly, training improved insulin action on thigh blood flow,
      and, furthermore, in both basal and insulin-stimulated muscle tissue, activities
      of Akt1 and GS and phosphorylation of AS160 increased with training (all P <
      0.05). In contrast, training reduced IRS-1-associated PI3-K activity (P < 0.05)
      in both basal and insulin-stimulated muscle tissue. Our findings do not support
      generally improved insulin signaling after endurance training; rather it seems
      that improved insulin-stimulated glucose uptake may result from hemodynamic
      adaptations as well as increased cellular protein content of individual insulin
      signaling components and molecules involved in glucose transport and metabolism.

PMID- 17513703
TI  - Association of the estrogen receptor-alpha gene with the metabolic syndrome and
      its component traits in African-American families: the Insulin Resistance
      Atherosclerosis Family Study.
AB  - OBJECTIVE: We previously detected an association between a region of the estrogen
      receptor-alpha (ESR1) gene and type 2 diabetes in an African-American case
      control study; thus, we investigated this region for associations with the
      metabolic syndrome and its component traits in African-American families from the
      Insulin Resistance Atherosclerosis Family Study. RESEARCH DESIGN AND METHODS: A
      total of 17 single nucleotide polymorphisms (SNPs) from a contiguous 41-kb intron
      1-intron 2 region of the ESR1 gene were genotyped in 548 individuals from 42
      African-American pedigrees. Generalized estimating equations were computed using
      a sandwich estimator of the variance and exchangeable correlation to account for
      familial correlation. RESULTS: Significant associations were detected between
      ESR1 SNPs and the metabolic syndrome (P = 0.005 to P = 0.029), type 2 diabetes (P
      = 0.001), insulin sensitivity (P = 0.0005 to P = 0.023), fasting insulin (P =
      0.022 to P = 0.033), triglycerides (P = 0.021), LDL (P = 0.016 to P = 0.034),
      cholesterol (P = 0.046), BMI (P = 0.016 to P = 0.035), waist circumference (P =
      0.012 to P = 0.023), and subcutaneous adipose tissue area (P = 0.016).
      CONCLUSIONS: It appears likely that ESR1 contributes to type 2 diabetes and CVD
      risk via pleiotropic effects, leading to insulin resistance, a poor lipid
      profile, and obesity.

PMID- 17513704
TI  - Surrogate markers of small fiber damage in human diabetic neuropathy.
AB  - Surrogate markers of diabetic neuropathy are being actively sought to facilitate
      the diagnosis, measure the progression, and assess the benefits of therapeutic
      intervention in patients with diabetic neuropathy. We have quantified small nerve
      fiber pathological changes using the technique of intraepidermal nerve fiber
      (IENF) assessment and the novel in vivo technique of corneal confocal microscopy
      (CCM). Fifty-four diabetic patients stratified for neuropathy, using neurological
      evaluation, neurophysiology, and quantitative sensory testing, and 15 control
      subjects were studied. They underwent a punch skin biopsy to quantify IENFs and
      CCM to quantify corneal nerve fibers. IENF density (IENFD), branch density, and
      branch length showed a progressive reduction with increasing severity of
      neuropathy, which was significant in patients with mild, moderate, and severe
      neuropathy. CCM also showed a progressive reduction in corneal nerve fiber
      density (CNFD) and branch density, but the latter was significantly reduced even
      in diabetic patients without neuropathy. Both IENFD and CNFD correlated
      significantly with cold detection and heat as pain thresholds. Intraepidermal and
      corneal nerve fiber lengths were reduced in patients with painful compared with
      painless diabetic neuropathy. Both IENF and CCM assessment accurately quantify
      small nerve fiber damage in diabetic patients. However, CCM quantifies small
      fiber damage rapidly and noninvasively and detects earlier stages of nerve damage
      compared with IENF pathology. This may make it an ideal technique to accurately
      diagnose and assess progression of human diabetic neuropathy.

PMID- 17513705
TI  - HLA-DPB1*0402 protects against type 1A diabetes autoimmunity in the highest risk
      DR3-DQB1*0201/DR4-DQB1*0302 DAISY population.
AB  - OBJECTIVE: A major goal in genetic studies of type 1A diabetes is prediction of
      anti-islet autoimmunity and subsequent diabetes in the general population, as
      >85% of patients do not have a first-degree relative with type 1A diabetes. Given
      prior association studies, we hypothesized that the strongest candidates for
      enhancing diabetes risk among DR3-DQB1*0201/DR4-DQB1*0302 individuals would be
      alleles of DP and DRB1*04 subtypes and, in particular, the absence of reportedly
      protective alleles DPB1*0402 and/or DRB1*0403. RESEARCH DESIGN AND METHODS: We
      genotyped 457 DR3-DQB1*0201/DR4-DQB1*0302 Diabetes Autoimmunity Study of the
      Young (DAISY) children (358 general population and 99 siblings/offspring of type
      1 diabetic patients) at the DPB1, DQB1, and DRB1 loci using linear arrays of
      immobilized sequence-specific oligonucleotides, with direct sequencing to
      differentiate DRB1*04 subtypes. RESULTS: By survival curve analysis of DAISY
      children, the risk of persistently expressing anti-islet autoantibodies is
      approximately 55% for relatives (children with a parent or sibling with type 1
      diabetes) in the absence of these two protective alleles vs. 0% (P = 0.02) with
      either protective allele, and the risk is 20 vs. 2% (P = 0.004) for general
      population children. Even when the population analyzed is limited to DR3
      DQB1*0201/DR4-DQB1*0302 children with DRB1*0401 (the most common DRB1*04
      subtype), DPB1*0402 influences development of anti-islet autoantibodies.
      CONCLUSIONS: The ability to identify a major group of general population newborns
      with a 20% risk of anti-islet autoimmunity should enhance both studies of the
      environmental determinants of type 1A diabetes and the design of trials for the
      primary prevention of anti-islet autoimmunity.

PMID- 17513706
TI  - 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates
      skeletal muscle 2-deoxyglucose uptake in healthy men.
AB  - Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise,
      metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and
      adiponectin increases glucose uptake. The aim of this study was to determine
      whether AICAR stimulates muscle glucose uptake in humans. We studied 29 healthy
      men (aged 26 +/- 8 years, BMI 25 +/- 4 kg/m(2) [mean +/- SD]). Rates of muscle 2
      deoxyglucose (2DG) uptake were determined by measuring accumulation of total
      muscle 2DG (2DG and 2DG-6-phosphate) during a primed, continuous 2DG infusion.
      The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG
      uptake were determined. Whole-body glucose disposal was compared before and
      during AICAR with the euglycemic-hyperinsulinemic clamp. Muscle 2DG uptake was
      linear over 9 h (R(2) = 0.88 +/- 0.09). After 3 h, 2DG uptake increased 2.1 +/-
      0.8- and 4.7 +/- 1.7-fold in response to AICAR or bicycle exercise, respectively.
      AMPK alpha(1) and alpha(2) activity or AMPK phosphorylation was unchanged after
      20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased
      immediately and 3 h after bicycle exercise. AICAR significantly increased
      phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation
      of beta-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or
      insulin receptor substrate-1 level was unchanged. Mean whole-body glucose
      disposal increased by 7% with AICAR from 9.3 +/- 0.6 to 10 +/- 0.6 mg x kg(-1) x
      min(-1) (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake
      with a minor effect on whole-body glucose disposal.

PMID- 17513707
TI  - Challenges in design of multicenter trials: end points assessed longitudinally
      for change and monotonicity.
AB  - OBJECTIVE: Assessing clinimetric performance of diabetic sensorimotor
      polyneuropathy (DSPN) end points in single and multicenter trials. RESEARCH
      DESIGN AND METHODS: Assessed were placebo-treated patients with DSPN in the
      Viatris and Eli Lilly trials and an epidemiologic cohort. RESULTS: Test
      reproducibility in clinical trial cohorts (r(I) approximately 0.7-0.85)
      approached that in the epidemiologic cohort (r(I) approximately 0.85-0.95).
      Associations between pairs of end points explained <10% of the variability of
      data (sometimes 15-35%), being higher in the epidemiologic cohort and the Viatris
      trial than in the Lilly trial. Most end points did not show monotonic worsening
      over 4 years. However, sural nerve amplitude and peroneal motor conduction
      velocity did. A nerve conduction score (Sigma 5 NC nds [5 attributes of nerve
      conduction expressed as normal deviates]) did not show monotonic worsening in
      established DSPN. In the epidemiologic cohort followed for 9.5 years, monotonic
      worsening of small magnitude occurred for sural amplitude, vibration detection
      threshold, and especially for composite quantitative sensation. CONCLUSIONS: The
      main reason why it is difficult to demonstrate monotonic worsening of neuropathic
      end points appears to be a very slow worsening of DSPN, a placebo effect for
      symptoms and signs, and measurement noise. Demonstrating disease progression in
      controlled trials of DSPN is more likely when 1) patients with developing rather
      than established DSPN are selected, 2) type 1 diabetic patients are
      preferentially recruited, 3) patients are selected who cannot or will not achieve
      ideal glycemic control, 4) end points chosen are known to show monotonic
      worsening, and 5) a restricted number of centers and expert examiners (trained,
      certified, using standard approaches, and reference values and interactive
      surveillance of tests) are used.

PMID- 17513708
TI  - Randomized study of basal-bolus insulin therapy in the inpatient management of
      patients with type 2 diabetes (RABBIT 2 trial).
AB  - OBJECTIVE: We sought to study the optimal management of hyperglycemia in non
      intensive care unit patients with type 2 diabetes, as few studies thus far have
      focused on the subject. RESEARCH DESIGN AND METHODS: We conducted a prospective,
      multicenter, randomized trial to compare the efficacy and safety of a basal-bolus
      insulin regimen with that of sliding-scale regular insulin (SSI) in patients with
      type 2 diabetes. A total of 130 insulin-naive patients were randomized to receive
      glargine and glulisine (n = 65) or a standard SSI protocol (n = 65). Glargine was
      given once daily and glulisine before meals at a starting dose of 0.4 units x kg(
      1) x day(-1) for blood glucose 140-200 mg/dl or 0.5 units x kg(-1) x day(-1) for
      blood glucose 201-400 mg/dl. SSI was given four times per day for blood glucose
      >140 mg/dl. RESULTS: The mean admission blood glucose was 229 +/- 6 mg/dl and A1C
      8.8 +/- 2%. A blood glucose target of <140 mg/dl was achieved in 66% of patients
      in the glargine and glulisine group and in 38% of those in the SSI group. The
      mean daily blood glucose between groups ranged from 23 to 58 mg/dl, with an
      overall blood glucose difference of 27 mg/dl (P < 0.01). Despite increasing
      insulin doses, 14% of patients treated with SSI remained with blood glucose >240
      mg/dl. There were no differences in the rate of hypoglycemia or length of
      hospital stay. CONCLUSIONS: Treatment with insulin glargine and glulisine
      resulted in significant improvement in glycemic control compared with that
      achieved with the use of SSI alone. Our study indicates that a basal-bolus
      insulin regimen is preferred over SSI in the management of non-critically ill,
      hospitalized patients with type 2 diabetes.

PMID- 17513709
TI  - Controlling the Ir genes.

PMID- 17513710
TI  - Complementation cloning of an MHC class II transactivator mutated in hereditary
      MHC class II deficiency (or bare lymphocyte syndrome). 1993.

PMID- 17513711
TI  - Telomerase in T lymphocytes: use it and lose it?
AB  - The enzyme telomerase counteracts telomere loss in proliferating cells and
      extends their capacity for replication. The importance of telomerase is
      highlighted by the award of the 2006 Albert Lasker Prize for Basic Medical
      Research for its discovery. Malignant cells subvert telomerase induction to their
      advantage, and up-regulation of this enzyme confers these populations with
      unlimited proliferative potential with obvious detrimental consequences. However
      this enzyme is also essential for the lifelong maintenance of normal cell
      populations that have a high rate of turnover. Thymic involution in early
      adulthood dictates that memory T cell populations have to be maintained by
      continuous proliferation. This highlights the inherent paradox that telomerase
      down-regulation in T cells may protect against malignancy yet also lead to
      replicative exhaustion of repeatedly activated memory T cells. In this article,
      we review the data on telomerase regulation in T lymphocytes and the implications
      this has for the maintenance of T cell memory.

PMID- 17513712
TI  - Cutting edge: CNS CD11c+ cells from mice with encephalomyelitis polarize Th17
      cells and support CD25+CD4+ T cell-mediated immunosuppression, suggesting dual
      roles in the disease process.
AB  - CD11c(+) dendritic cells (DCs) are a prominent component of CNS infiltrates in
      mice with experimental autoimmune encephalomyelitis. However, their role in
      immunopathogenesis is controversial. In this study, we report that they originate
      from peripheral hemopoietic cells and exhibit diverse functions that change
      during the course of acute disease. CNS DCs stimulate naive T cells to
      proliferate and polarize Th(17) responses when harvested shortly following
      disease onset but are relatively inefficient APC by the time of peak disability.
      Conversely, they can support CD4(+)CD25(+) T cell-mediated immunosuppression
      early during experimental autoimmune encephalomyelitis. Such paradoxical
      functions might reflect dual roles of CNS DCs in promoting local inflammation
      while setting the stage for remission.

PMID- 17513713
TI  - Cutting edge: small molecule CD40 ligand mimetics promote control of parasitemia
      and enhance T cells producing IFN-gamma during experimental Trypanosoma cruzi
      infection.
AB  - Host resistance to Trypanosoma cruzi infection depends on a type 1 response
      characterized by a strong production of IL-12 and IFN-gamma. Amplifying this
      response through CD40 triggering results in control of parasitemia. Two newly
      synthesized molecules (<3 kDa) mimicking trimeric CD40L (mini CD40Ls(-1) and (
      2)) bind to CD40, activate murine dendritic cells, and elicit IL-12 production.
      Wild-type but not CD40 knockout mice exhibited a sharp decrease of parasitemia
      and mortality when inoculated with T. cruzi mixed with miniCD40Ls. Moreover, the
      immunosuppression induced by T. cruzi infection was impaired in mice treated with
      miniCD40Ls, as shown by proliferation of splenic lymphocytes, percentage of
      CD8(+) T cells, and IFN-gamma production. Mice surviving T. cruzi infection in
      the presence of miniCD40L(-1) were immunized against a challenge infection. Our
      results indicate that CD40L mimetics are effective in vivo and promote the
      control of T. cruzi infection by overcoming the immunosuppression usually induced
      by the parasites.

PMID- 17513714
TI  - Cutting edge: involvement of the type I IFN production and signaling pathway in
      lipopolysaccharide-induced IL-10 production.
AB  - Macrophages respond to LPS by the rapid activation of proinflammatory cytokines
      that serve to initiate host defense against microbial invasion. To prevent injury
      to the host from excess production of these cytokines, IL-10 is up-regulated to
      feedback inhibit the proinflammatory response. However, the molecular events
      responsible for LPS-induced up-regulation of IL-10 remain to be elucidated. In
      this study, we provide evidence that production of and signaling by type I IFN is
      required for LPS-induced IL-10 up-regulation. In addition, we demonstrate that
      defect in type I IFN production and signaling results in a trend toward LPS
      mediated superinduction of proinflammatory genes and cytokines in bone marrow
      derived macrophages. Our findings suggest a novel anti-inflammatory role for the
      type I IFN production and signaling pathway in regulating LPS response in bone
      marrow-derived macrophages.

PMID- 17513715
TI  - Cutting edge: cross-regulation by TLR4 and T cell Ig mucin-3 determines sex
      differences in inflammatory heart disease.
AB  - Recent clinical studies have reinforced the importance of sex-related differences
      in the pathogenesis of cardiovascular diseases, with an increased incidence and
      mortality in men. Similar to humans, male BALB/c mice infected with
      coxsackievirus B3 (CVB3) develop more severe inflammation in the heart even
      though viral replication is no greater than in females. We show that TLR4 and IFN
      gamma levels are significantly elevated and regulatory T cell (Treg) populations
      significantly reduced in the heart of males following CVB3 infection, whereas
      females have significantly increased T cell Ig mucin (Tim)-3, IL-4 and Treg.
      Blocking Tim-3 in males significantly increases inflammation and TLR4 expression
      while reducing Treg. In contrast, defective TLR4 signaling significantly reduces
      inflammation while increasing Tim-3 expression. Cross-regulation of TLR4 and Tim
      3 occurs during the innate and adaptive immune response. This novel mechanism may
      help explain why inflammatory heart disease is more severe in males.

PMID- 17513716
TI  - Cutting edge: TLR2 directly triggers Th1 effector functions.
AB  - Toll-like receptors recognize pathogen-associated molecular patterns, activate
      innate immunity, and consequently modulate adaptive immunity in response to
      infections. TLRs are also expressed on T cells, and it has been shown that T cell
      activation is modulated by TLR ligands. However, the functions of TLRs on Th1 and
      Th2 effector cells and the molecular mechanisms underlying TLR-mediated
      activation are not fully understood. We analyzed TLR functions and downstream
      signaling events in both effector T cells. In mouse Th1 cells the stimulation by
      TLR2 but not by other TLRs directly induced IFN-gamma production, cell
      proliferation, and cell survival without TCR stimulation, and these effects were
      greatly enhanced by IL-2 or IL-12 through the enhanced activation of MAPKs. In
      contrast, no TLR affected the function of effector Th2 cells. These results
      identify TLR2 as a new specific activator of Th1 cell function and imply the
      involvement in Th1-mediated responses.

PMID- 17513717
TI  - Cutting edge: direct action of thymic stromal lymphopoietin on activated human
      CD4+ T cells.
AB  - Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4(+) T cell
      homeostasis and contributes to allergic and inflammatory responses. TSLP can act
      directly on mouse CD4(+) T cells, but in humans, the available data have
      indicated that TSLP receptors are not expressed on CD4(+) T cells and that TSLP
      instead activates dendritic cells, which in turn promote the proliferation and
      differentiation of CD4(+) T cells. We now unexpectedly demonstrate the presence
      of TSLP receptors on activated human CD4(+) T cells. Strikingly, whereas freshly
      isolated peripheral blood human T cells show little if any response to TSLP, TCR
      stimulation allows a potent response to this cytokine. Moreover, TSLP increases
      the sensitivity of human CD4(+) T cells to low doses of IL-2, augmenting
      responsiveness of these cells to TCR engagement. Our results establish that human
      CD4(+) T cells are direct targets for TSLP.

PMID- 17513718
TI  - Cutting edge: regulatory T cells induce CD4+CD25-Foxp3- T cells or are self
      induced to become Th17 cells in the absence of exogenous TGF-beta.
AB  - Recent studies have shown that TGF-beta together with IL-6 induce the
      differentiation of IL-17-producing T cells (Th17) T cells. We therefore examined
      whether CD4(+)CD25(+)Foxp3(+) regulatory T cells, i.e., cells previously shown to
      produce TGF-beta, serve as Th17 inducers. We found that upon activation purified
      CD25(+) T cells (or sorted GFP(+) T cells obtained from Foxp3-GFP knockin mice)
      produce high amounts of soluble TGF-beta and when cultured with CD4(+)CD25(
      )Foxp3(-) T cells in the presence of IL-6 induce the latter to differentiate into
      Th17 cells. Perhaps more importantly, upon activation,
      CD4(+)CD25(+)Foxp3(+)(GFP(+)) T cells themselves differentiate into Th17 cells in
      the presence of IL-6 (and in the absence of exogenous TGF-beta). These results
      indicate that CD4(+)CD25(+)Foxp3(+) regulatory T cells can function as inducers
      of Th17 cells and can differentiate into Th17 cells. They thus have important
      implications to our understanding of regulatory T cell function and their
      possible therapeutic use.

PMID- 17513719
TI  - Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in
      the tumor microenvironment.
AB  - Th17 cells play an active role in inflammation and autoimmune diseases. However,
      the nature and regulation of Th17 in the context of tumor immunity remain
      unknown. In this study, we show that parallel to regulatory T (Treg) cells, IL
      17(+) CD4(+) and CD8(+) T cells are kinetically induced in multiple tumor
      microenvironments in mice and humans. Treg cells play a crucial role in tumor
      immune pathogenesis and temper immune therapeutic efficacy. IL-2 is crucial for
      the production and function of Treg cells. We now show that IL-2 reduces IL-17(+)
      T cell differentiation in the tumor microenvironment accompanied with an enhanced
      Treg cell compartment in vitro and in vivo. Altogether, our work demonstrates a
      dynamic differentiation of IL-17(+) T cells in the tumor microenvironment,
      reveals a novel role for IL-2 in controlling the balance between IL-17(+) and
      Treg cells, and provides new insight of IL-17(+) T cells in tumor immune
      pathology and therapy.

PMID- 17513720
TI  - An essential role for TNF in modulating thresholds for survival, activation, and
      tolerance of CD8+ T cells.
AB  - TNF and its receptors p55 and p75 are known to be important in the homeostasis of
      the peripheral immune system. Previous studies have presented apparently
      contradictory evidence for an in vivo role of TNF in T cells. In this study, we
      analyzed TNF-deficient mice crossed with the F5 TCR-transgenic animals. We show
      that endogenous TNF modulates several aspects of homeostasis of peripheral F5 CD8
      T cells. We found that F5/TNF(-/-)mice had reduced numbers of peripheral F5 T
      cells, F5/TNF(-/-) CD8 T cells exhibited reduced survival potential, and
      furthermore that T cell-derived TNF is required for optimum recovery of naive CD8
      T cells in lymphopenic hosts, suggesting its involvement in the survival of
      peripheral CD8 T cells. Both peptide activation and ensuing Ag-induced apoptosis
      are quantitatively reduced in TNF(-/-) CD8 T cells. The latter observations can
      be related to decreased binding activities of NF-kappaB and NF-ATp observed in Ag
      stimulated F5/TNF(-/-) T cells. Finally, in a CD8 T cell tolerance model,
      endogenous TNF was necessary for several parameters of CD8 T cell tolerance
      induction. Collectively, our results provide evidence that endogenous TNF
      modulates thresholds in several ligand-driven T cell responses.

PMID- 17513721
TI  - Normal hemopoiesis and lymphopoiesis in the combined absence of numb and
      numblike.
AB  - The mammalian ortholog of the conserved Drosophila adaptor protein Numb (Nb) and
      its homolog Numblike (Nbl) modulate neuronal cell fate determination at least in
      part by antagonizing Notch signaling. Because the Notch pathway has been
      implicated in regulating hemopoietic stem cell self-renewal and T cell fate
      specification in mammals, we investigated the role of Nb and Nbl in hemopoiesis
      using conditional gene targeting. Surprisingly simultaneous deletion of both Nb
      and Nbl in murine bone marrow precursors did not affect the ability of stem cells
      to self-renew or to give rise to differentiated myeloid or lymphoid progeny, even
      under competitive conditions in mixed chimeras. Furthermore, T cell fate
      specification and intrathymic T cell development were unaffected in the combined
      absence of Nb and Nbl. Collectively our data indicate that the Nb family of
      adaptor proteins is dispensable for hemopoiesis and lymphopoiesis in mice,
      despite their proposed role in neuronal stem cell development.

PMID- 17513722
TI  - Signal 3 availability limits the CD8 T cell response to a solid tumor.
AB  - CD8 T cells need a third signal, along with Ag and costimulation, for effective
      survival and development of effector functions, and this can be provided by IL-12
      or type I IFN. Adoptively transferred OT-I T cells, specific for H-2K(b) and OVA,
      encounter Ag in the draining lymph nodes of mice with the OVA-expressing E.G7
      tumor growing at a s.c. site. The OT-I cells respond by undergoing limited clonal
      expansion and development of effector functions (granzyme B expression and IFN
      gamma production), and they migrate to the tumor where they persist but fail to
      control tumor growth. In contrast, OT-I T cells deficient for both the IL-12 and
      type I IFN receptors expand only transiently and rapidly disappear. These results
      suggested that some signal 3 cytokine is available, but that it is insufficient
      to support a CTL response that can control tumor growth. Consistent with this,
      administration of IL-12 at day 10 of tumor growth resulted in a large and
      sustained expansion of wild-type OT-I cells with enhanced effector functions, and
      tumor growth was controlled. This did not occur when the OT-I cells lacked the IL
      12 and type I IFN receptors, demonstrating that the therapeutic effect of IL-12
      results from direct delivery of signal 3 to the CD8 T cells responding to tumor
      Ag in the signal 3-deficient environment of the tumor.

PMID- 17513723
TI  - Comparative prime-boost vaccinations using Semliki Forest virus, adenovirus, and
      ALVAC vectors demonstrate differences in the generation of a protective central
      memory CTL response against the P815 tumor.
AB  - Tumor-specific Ags are potential target molecules in the therapeutic treatment of
      cancer. One way to elicit potent immune responses against these Ags is to use
      recombinant viruses, which activate both the innate and the adaptive arms of the
      immune system. In this study, we have compared Semliki Forest virus (SFV),
      adenovirus, and ALVAC (poxvirus) vectors for their capacity to induce CD8(+) T
      cell responses against the P1A tumor Ag and to elicit protection against
      subsequent challenge injection of P1A-expressing P815 tumor cells in DBA/2 mice.
      Both homologous and heterologous prime-boost regimens were studied. In most
      cases, both higher CD8(+) T cell responses and better tumor protections were
      observed in mice immunized with heterologous prime-boost regimens, suggesting
      that the combination of different viral vectors is beneficial for the induction
      of an effective immune response. However, homologous immunization with SFV
      provided potent tumor protection despite a rather moderate primary CD8(+) T cell
      response as compared with mice immunized with recombinant adenovirus. SFV
      immunized mice showed a rapid and more extensive expansion of P1A-specific CD8(+)
      T cells in the tumor-draining lymph node after tumor challenge and had a higher
      frequency of CD62L(+) P1A-specific T cells in the blood, spleen, and lymph nodes
      as compared with adenoimmunized mice. Our results indicate that not only the
      magnitude but in particular the quality of the CD8(+) T cell response correlates
      with tumor protection.

PMID- 17513724
TI  - Lack of essential role of NF-kappa B p50, RelA, and cRel subunits in virus
      induced type 1 IFN expression.
AB  - Type 1 IFNs (IFN-alphabeta) play pivotal roles in the host antiviral response and
      in TLR-induced signaling. IFN regulatory factor (IRF) and NF-kappaB transcription
      factors are thought to be crucial for virus-induced mRNA expression of IFN-beta.
      Although recent studies have demonstrated essential roles for IRF3 and IRF7, the
      definitive role of NF-kappaB factors in IFN-beta (or IFN-alpha) expression
      remains unknown. Using mice deficient in distinct members of the NF-kappaB
      family, we investigated NF-kappaB function in regulating type 1 IFN expression in
      response to Sendai virus and Newcastle disease virus infection. Surprisingly, IFN
      beta and IFN-alpha expression was strongly induced following virus infection of
      mouse embryonic fibroblasts (MEFs) from p50(-/-), RelA/p65(-/-), cRel(-/-), p50(
      /-)cRel(-/-), and p50(-/-)RelA(-/-) mice. Compared with wild-type MEFs, only
      RelA(-/-) and p50(-/-)RelA(-/-) MEFs showed a modest reduction in IFN-beta
      expression. To overcome functional redundancy between different NF-kappaB
      subunits, we expressed a dominant-negative IkappaBalpha protein in p50(-/-)RelA(
      /-) MEFs to inhibit activation of remaining NF-kappaB subunits. Although viral
      infection of these cells failed to induce detectable NF-kappaB activity, both
      Sendai virus and Newcastle disease virus infection led to robust IFN-beta
      expression. Virus infection of dendritic cells or TLR9-ligand CpG-D19 treatment
      of plasmacytoid dendritic cells from RelA(-/-) or p50(-/-)cRel(-/-) mice also
      induced robust type 1 IFN expression. Our findings therefore indicate that NF
      kappaB subunits p50, RelA, and cRel play a relatively minor role in virus-induced
      type 1 IFN expression.

PMID- 17513725
TI  - Distinct roles of different NF-kappa B subunits in regulating inflammatory and T
      cell stimulatory gene expression in dendritic cells.
AB  - TLRs play a critical role in inducing inflammatory and immune responses against
      microbial agents. In this study, we have investigated the role of NF-kappaB
      transcription factors in regulating TLR-induced gene expression in dendritic
      cells, a key APC type. The p50 and cRel NF-kappaB subunits were found to be
      crucial for regulating genes important for dendritic cell-induced T cell
      responses (e.g., CD40, IL-12, and IL-18) but not for genes encoding inflammatory
      cytokines (e.g., TNF-alpha, IL-1alpha, and IL-6). In striking contrast, the RelA
      subunit was crucial for expression of inflammatory cytokine genes but not T cell
      stimulatory genes. These novel findings reveal a fundamentally important
      difference in biological function of genes regulated by different NF-kappaB
      subunits. Focusing on RelA target gene specificity mechanisms, we investigated
      whether the kappaB site and/or the unique composition of RelA played the most
      crucial role. Surprisingly, studies of IL-6 expression showed that the kappaB
      site is not a primary determinant of RelA target gene specificity. Instead, a
      major specificity mechanism is the unique ability of RelA to interact with the
      transcriptional coactivator CREB-binding protein, a function not shared with the
      closely related cRel subunit. Together, our findings indicate novel and
      critically important overall roles of NF-kappaB in TLR-induced gene expression
      that are mediated by unique functions of distinct subunits.

PMID- 17513726
TI  - Detection and long-term in vivo monitoring of individual tumor-specific T cell
      clones in patients with metastatic melanoma.
AB  - We investigated the presence of individual melanoma-specific T cell clones in
      patients with metastatic melanoma. Ten patients were examined for the presence of
      melanoma-reactive T cells using dendritic cells loaded with autologous tumor
      cells. Their specificity was tested using nonradioactive cytotoxicity test.
      Individual immunodominant T cell clones were identified by the clonotypic assay
      that combines in vitro cell culture, immunomagnetic sorting of activated IFN
      gamma(+) T cells, TCRbeta locus-anchored RT-PCR, and clonotypic quantitative PCR.
      All patients had detectable melanoma-reactive T cells in vitro. Expanded melanoma
      reactive T cells demonstrated specific cytotoxic effect against autologous tumor
      cells in vitro. Three patients experienced objective responses, and their
      clinical responses were closely associated with the in vivo expansion and long
      term persistence of individual CD8(+) T cell clones with frequencies of 10(-6) to
      10(-3) of all circulating CD8(+) T cells. Five patients with progressive disease
      experienced no or temporary presence of circulating melanoma-reactive T cell
      clones. Thus, circulating immunodominant CD8(+) T cell clones closely correlate
      with clinical outcome in patients with metastatic melanoma.

PMID- 17513727
TI  - Redundant role for early growth response transcriptional regulators in thymocyte
      differentiation and survival.
AB  - The early growth response (Egr) family of transcriptional regulators consists of
      four proteins that share highly conserved DNA-binding domains. In many cell
      types, they are coexpressed and appear to have cooperative roles in regulating
      gene expression during growth and differentiation. Three Egr proteins, Egr1,
      Egr2, and Egr3, are induced during thymocyte differentiation in response to pre
      TCR signaling, suggesting they may be critical for some aspects of pre-TCR
      mediated differentiation. Indeed, enforced expression of Egr proteins in
      developing thymocytes can recapitulate some aspects of pre-TCR signaling, but the
      mechanisms by which they contribute to beta-selection are still poorly
      understood. Egr3 stimulates proliferation of beta-selected thymocytes, and Egr3
      deficient mice have hypocellular thymuses, defects in proliferation, and impaired
      progression from double-negative 3 to double-negative 4. Surprisingly, Egr1
      deficient mice exhibit normal beta-selection, indicating that the functions of
      Egr1 during beta-selection are likely compensated by other Egr proteins. In this
      study, we show that mice lacking both Egr1 and Egr3 exhibit a more severe thymic
      atrophy and impairment of thymocyte differentiation than mice lacking either Egr1
      or Egr3. This is due to a proliferation defect and cell-autonomous increase in
      apoptosis, indicating that Egr1 and Egr3 cooperate to promote thymocyte survival.
      Microarray analysis of deregulated gene expression in immature thymocytes lacking
      both Egr1 and Egr3 revealed a previously unknown role for Egr proteins in the
      maintenance of cellular metabolism, providing new insight into the function of
      these molecules during T cell development.

PMID- 17513728
TI  - Th17 augmentation in OTII TCR plus T cell-selective type 1 sphingosine 1
      phosphate receptor double transgenic mice.
AB  - Sphingosine 1-phosphate (S1P) in blood and lymph controls lymphoid traffic and
      tissue migration of T cells through signals from the type 1 S1PR (S1P(1)), but
      less is known of effects of the S1P-S1P(1) axis on nonmigration functions of T
      cells. CD4 T cells from a double transgenic (DTG) mouse express OTII TCRs
      specific for OVA peptide 323-339 (OVA) and a high level of transgenic S1P(1),
      resistant to suppression by T cell activation. OVA-activated DTG CD4 T cells
      respond as expected to S1P by chemotactic migration and reduction in secretion of
      IFN-gamma. In addition, DTG CD4 T cells stimulated by OVA secrete a mean of 2.5
      fold more IL-17 than those from OTII single transgenic mice with concomitantly
      higher levels of mRNA encoding IL-17 by real-time PCR and of CD4 T cells with
      intracellular IL-17 detected by ELISPOT assays. OVA challenge of s.c. air pockets
      elicited influx of more OTII TCR-positive T cells producing a higher level of IL
      17 in DTG mice than OTII control mice. Augmentation of the number and activity of
      Th17 cells by the S1P-S1P(1) axis may thus enhance host defense against microbes
      and in other settings increase host susceptibility to autoimmune diseases.

PMID- 17513729
TI  - Vaccinia virus-specific CD4+ T cell responses target a set of antigens largely
      distinct from those targeted by CD8+ T cell responses.
AB  - Recent studies have defined vaccinia virus (VACV)-specific CD8(+) T cell epitopes
      in mice and humans. However, little is known about the epitope specificities of
      CD4(+) T cell responses. In this study, we identified 14 I-A(b)-restricted VACV
      specific CD4(+) T cell epitopes by screening a large set of 2146 different 15-mer
      peptides in C57BL/6 mice. These epitopes account for approximately 20% of the
      total anti-VACV CD4(+) T cell response and are derived from 13 different viral
      proteins. Surprisingly, none of the CD4(+) T cell epitopes identified was derived
      from VACV virulence factors. Although early Ags were recognized, late Ags
      predominated as CD4(+) T cell targets. These results are in contrast to what was
      previously found in CD8(+) T cells responses, where early Ags, including
      virulence factors, were prominently recognized. Taken together, these results
      highlight fundamental differences in immunodominance of CD4(+) and CD8(+) T cell
      responses to a complex pathogen.

PMID- 17513730
TI  - Human CD5 protects circulating tumor antigen-specific CTL from tumor-mediated
      activation-induced cell death.
AB  - We previously characterized several tumor-specific T cell clones from PBL and
      tumor-infiltrating lymphocytes of a lung cancer patient with identical TCR
      rearrangements and similar lytic potential, but with different antitumor
      response. A role of the TCR inhibitory molecule CD5 to impair reactivity of
      peripheral T cells against the tumor was found to be involved in this process. In
      this report, we demonstrate that CD5 also controls the susceptibility of specific
      T cells to activation-induced cell death (AICD) triggered by the tumor. Using a
      panel of tumor-infiltrating lymphocytes and PBL-derived clones expressing
      different levels of CD5, our results indicate that T lymphocyte AICD in response
      to the cognate tumor is inversely proportional to the surface expression level of
      CD5. They also suggest a direct involvement of CD5 in this process, as revealed
      by an increase in tumor-mediated T lymphocyte AICD following neutralization of
      the molecule with specific mAb. Mechanistically, our data indicate that down
      regulation of FasL expression and subsequent inhibition of caspase-8 activation
      are involved in CD5-induced T cell survival. These results provide evidence for a
      role of CD5 in the fate of peripheral tumor-specific T cells and further suggest
      its contribution to regulate the extension of CTL response against tumor.

PMID- 17513731
TI  - Regulation of cell adhesion by affinity and conformational unbending of
      alpha4beta1 integrin.
AB  - Rapid activation of integrins in response to chemokine-induced signaling serves
      as a basis for leukocyte arrest on inflamed endothelium. Current models of
      integrin activation include increased affinity for ligand, molecular extension,
      and others. In this study, using real-time fluorescence resonance energy transfer
      to assess alpha(4)beta(1) integrin conformational unbending and fluorescent
      ligand binding to assess affinity, we report at least four receptor states with
      independent regulation of affinity and unbending. Moreover, kinetic analysis of
      chemokine-induced integrin conformational unbending and ligand-binding affinity
      revealed conditions under which the affinity change was transient whereas the
      unbending was sustained. In a VLA-4/VCAM-1-specific myeloid cell adhesion model
      system, changes in the affinity of the VLA-4-binding pocket were reflected in
      rapid cell aggregation and disaggregation. However, the initial rate of cell
      aggregation increased 9-fold upon activation, of which only 2.5-fold was
      attributable to the increased affinity of the binding pocket. These data show
      that independent regulation of affinity and conformational unbending represents a
      novel and fundamental mechanism for regulation of integrin-dependent adhesion in
      which the increased affinity appears to account primarily for the increasing
      lifetime of the alpha(4)beta(1) integrin/VCAM-1 bond, whereas the unbending
      accounts for the increased capture efficiency.

PMID- 17513732
TI  - CD4+CD25+ T regulatory cells dominate multiple immune evasion mechanisms in early
      but not late phases of tumor development in a B cell lymphoma model.
AB  - Tumors use a complex set of direct and indirect mechanisms to evade the immune
      system. Naturally arising CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells have
      been implicated recently in tumor immune escape mechanism, but the relative
      contribution of these cells to overall tumor progression compared with other
      immune evasion mechanisms remains to be elucidated. Using the A20 B cell lymphoma
      as a transplantable tumor model, we demonstrate that this tumor employs multiple
      direct (expression of immunoinhibitory molecule PD-L1, IDO, and IL-10, and lack
      of expression of CD80 costimulatory molecule) and indirect (down-regulation of
      APC function and induction of Treg cells) immune evasion mechanisms. Importantly,
      Treg cells served as the dominant immune escape mechanism early in tumor
      progression because the physical elimination of these cells before tumor
      challenge resulted in tumor-free survival in 70% of mice, whereas their depletion
      in animals with established tumors had no therapeutic effect. Therefore, our data
      suggest that Treg cells may serve as an important therapeutic target for patients
      with early stages of cancer and that more vigorous combinatorial approaches
      simultaneously targeting multiple immune evasion as well as immunosurveillance
      mechanisms for the generation of a productive immune response against tumor may
      be required for effective immunotherapy in patients with advanced disease.

PMID- 17513733
TI  - Induction of tolerance in CD8+ T cells to a transgenic autoantigen expressed in
      the liver does not require cross-presentation.
AB  - Cross-presentation of normal self and candidate tumor Ags by bone marrow (BM)
      derived APCs that have not been activated has been demonstrated as a major
      mechanism contributing to acquisition of tolerance by mature T cells that first
      encounter an Ag in the periphery (cross-tolerance). Following adoptive transfer
      of naive TCR-transgenic CD8(+) T cells into a host expressing a transgenic Ag
      that is a potentially targetable tumor Ag in normal hepatocytes as a self-Ag, we
      found that the majority of Ag-specific CD8(+) T cells were deleted, with the
      remaining cells rendered anergic. Studies in BM chimeric mice and with purified
      cell populations demonstrated that these events were not dependent on cross
      presentation by BM-derived APCs including Kupffer cells or liver sinusoidal
      endothelial cells, and apparently can occur entirely as a consequence of direct
      recognition of Ag endogenously processed and presented by hepatocytes. Direct
      recognition of Ag-expressing hepatocytes in vivo induced a proliferative response
      and up-regulation of activation markers in responding CD8(+) T cells, but
      proliferating cells did not accumulate, with most cells rapidly eliminated, and
      the persisting T cells lost the capacity to proliferate in response to repeated
      Ag stimulation. The results suggest that parenchymal tissues may retain the
      capacity to directly regulate in vivo responses to self-Ags processed and
      presented in the context of class I MHC molecules.

PMID- 17513734
TI  - CD103- and CD103+ bronchial lymph node dendritic cells are specialized in
      presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells.
AB  - Dendritic cells (DC) are able to capture, process, and present exogenous Ag to
      CD8(+) T lymphocytes through MHC class I, a process referred to as cross
      presentation. In this study, we demonstrate that CD103(+) (CD11c(high)CD11b(low))
      and CD103(-) (CD11c(int)CD11b(high)) DC residing in the lung-draining bronchial
      lymph node (brLN) have evolved to acquire opposing functions in presenting
      innocuous inhaled Ag. Thus, under tolerogenic conditions, CD103(-) DC are
      specialized in presenting innocuous Ag to CD4(+) T cells, whereas CD103(+) DC,
      which do not express CD8alpha, are specialized in presenting Ag exclusively to
      CD8(+) T cells. In CCR7-deficient but not in plt/plt mice, Ag-carrying CD103(+)
      DC are largely absent in the brLN, although CD103(+) DC are present in the lung
      of CCR7-deficient mice. As a consequence, adoptively transferred CD8(+) T cells
      can be activated under tolerizing conditions in plt/plt but not in CCR7-deficient
      mice. These data reveal that CD103(+) brLN DC are specialized in cross-presenting
      innocuous inhaled Ag in vivo. Because these cells are largely absent in CCR7(-/-)
      mice, our findings strongly suggest that brLN CD103(+) DC are lung-derived and
      that expression of CCR7 is required for their migration from the lung into its
      draining lymph node.

PMID- 17513735
TI  - Tumor exosomes inhibit differentiation of bone marrow dendritic cells.
AB  - The production of exosomes by tumor cells has been implicated in tumor-associated
      immune suppression. In this study, we show that, in mice, exosomes produced by
      TS/A murine mammary tumor cells target CD11b(+) myeloid precursors in the bone
      marrow (BM) in vivo, and that this is associated with an accumulation of myeloid
      precursors in the spleen. Moreover, we demonstrate that TS/A exosomes block the
      differentiation of murine myeloid precursor cells into dendritic cells (DC) in
      vitro. Addition of tumor exosomes at day 0 led to a significant block of
      differentiation into DC, whereas addition at later time points was less
      effective. Similarly, exosomes produced by human breast tumor cells inhibited the
      differentiation of human monocytes in vitro. The levels of IL-6 and
      phosphorylated Stat3 were elevated 12 h after the tumor exosome stimulation of
      murine myeloid precursors, and tumor exosomes were less effective in inhibiting
      differentiation of BM cells isolated from IL-6 knockout mice. Addition of a rIL-6
      to the IL-6 knockout BM cell culture restored the tumor exosome-mediated
      inhibition of DC differentiation. These data suggest that tumor exosome-mediated
      induction of IL-6 plays a role in blocking BM DC differentiation.

PMID- 17513736
TI  - Murine dendritic cell type I IFN production induced by human IgG-RNA immune
      complexes is IFN regulatory factor (IRF)5 and IRF7 dependent and is required for
      IL-6 production.
AB  - Dendritic cell (DC) activation by nucleic acid-containing IgG complexes is
      implicated in systemic lupus erythematosus (SLE) pathogenesis. However, it has
      been difficult to definitively examine the receptors and signaling pathways by
      which this activation is mediated. Because mouse FcgammaRs recognize human IgG,
      we hypothesized that IgG from lupus patients might stimulate mouse DCs, thereby
      facilitating this analysis. In this study, we show that sera and purified IgG
      from lupus patients activate mouse DCs to produce IFN-alpha, IFN-beta, and IL-6
      and up-regulate costimulatory molecules in a FcgammaR-dependent manner. This
      activation is only seen in sera with reactivity against ribonucleoproteins and is
      completely dependent on TLR7 and the presence of RNA. As anticipated, IFN
      regulatory factor (IRF)7 is required for IFN-alpha and IFN-beta production.
      Unexpectedly, however, IRF5 plays a critical role in IFN-alpha and IFN-beta
      production induced not only by RNA-containing immune complexes but also by
      conventional TLR7 and TLR9 ligands. Moreover, DC production of IL-6 induced by
      these stimuli is dependent on a functional type I IFNR, indicating the need for a
      type I IFN-dependent feedback loop in the production of inflammatory cytokines.
      This system may also prove useful for the study of receptors and signaling
      pathways used by immune complexes in other human diseases.

PMID- 17513737
TI  - Type 2 diabetes impairs insulin receptor substrate-2-mediated
      phosphatidylinositol 3-kinase activity in primary macrophages to induce a state
      of cytokine resistance to IL-4 in association with overexpression of suppressor
      of cytokine signaling-3.
AB  - Chronic elevation of proinflammatory markers in type 2 diabetes (T2D) is well
      defined, but the role of anti-inflammatory cytokines in T2D is less clear. In
      this study, we report that normal IL-4-dependent elaboration of IL-1 receptor
      antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages.
      We also show that macrophages isolated from obese/diabetic db/db mice have
      impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor
      of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory
      function. Peritoneal proinflammatory cytokine levels were examined in diabese
      (db/db) mice, and IL-6 was found to be nearly 7-fold higher than in nondiabese
      (db/+) control mice. Resident peritoneal macrophages were isolated from db/db
      mice and were found to constitutively overexpress IL-6 and were unable to
      elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. Inhibition of
      PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell
      permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA
      production in db/+ macrophages. Examination of IL-4 signaling in db/db
      macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2
      tyrosine phosphorylation was reduced compared with db/+ macrophages. SOCS-3/IL-4
      receptor complexes, however, were increased in db/db mouse macrophages compared
      with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. These
      results indicate that in the db/db mouse model of T2D, macrophage expression of
      SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a
      state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA.

PMID- 17513738
TI  - The CD28/CTLA-4-B7 signaling pathway is involved in both allergic sensitization
      and tolerance induction to orally administered peanut proteins.
AB  - Dendritic cells are believed to play an essential role in regulating the balance
      between immunogenic and tolerogenic responses to mucosal Ags by controlling T
      cell differentiation and activation via costimulatory and coinhibitory signals.
      The CD28/CTLA-4-CD80/CD86 signaling pathway appears to be one of the most
      important regulators of T cell responses but its exact role in responses to
      orally administered proteins remains to be elucidated. In the present study, the
      involvement of the CD28/CTLA-4-CD80/CD86 costimulatory pathway in the induction
      of allergic sensitization and oral tolerance to peanut proteins was investigated.
      In both an established C3H/HeOuJ mouse model of peanut hypersensitivity and an
      oral tolerance model to peanut, CD28/CTLA-4-CD80/CD86 interactions were blocked
      using the fusion protein CTLA-4Ig. To examine the relative contribution of CD80-
      and CD86-mediated costimulation in these models, anti-CD80 and anti-CD86 blocking
      Abs were used. In the hypersensitivity model, CTLA-4Ig treatment prevented the
      development of peanut extract-induced cytokine responses, peanut extract-specific
      IgG1, IgG2a, and IgE production and peanut extract-induced challenge responses.
      Blocking of CD80 reduced, whereas anti-CD86 treatment completely inhibited, the
      induction of peanut extract-specific IgE. Normal tolerance induction to peanut
      extract was found following CTLA-4Ig, anti-CD86, or anti-CD80 plus anti-CD86
      treatment, whereas blockade of CD80 impaired the induction of oral tolerance. We
      show that CD28/CTLA-4-CD80/CD86 signaling is essential for the development of
      allergic responses to peanut and that CD86 interaction is most important in
      inducing peanut extract-specific IgE responses. Additionally, our data suggest
      that CD80 but not CD86 interaction with CTLA-4 is crucial for the induction of
      low dose tolerance to peanut.

PMID- 17513739
TI  - Distinct subsets of FoxP3+ regulatory T cells participate in the control of
      immune responses.
AB  - Expression of the transcription factor FoxP3 is the hallmark of regulatory T
      cells that play a crucial role in dampening immune responses. A comparison of the
      development and phenotype of FoxP3(+) T cells in relation to the expression of
      conventional MHC molecules facilitated the identification of several distinct
      lineages of naive and effector/memory populations of Foxp3(+) T cells. One
      subpopulation of effector/memory Foxp3(+) T cells develops in the thymic medulla,
      whereas the second is thymic independent. Both lineages display a distinct
      activated phenotype, undergo extensive steady-state proliferation, home to sites
      of acute inflammation, and are unique in their capacity to mediate Ag-nonspecific
      suppression of T cell activation directly ex vivo. Effector FoxP3(+) T cells may
      act as a sentinel of tolerance, providing a first line of defense against
      potentially harmful responses by rapidly suppressing immunity to peripheral self
      Ags.

PMID- 17513740
TI  - Altered innate immune functioning of dendritic cells in elderly humans: a role of
      phosphoinositide 3-kinase-signaling pathway.
AB  - Aging represents a state of paradox where chronic inflammation is associated with
      declining immune responses. Dendritic cells (DCs) are the major APCs responsible
      for initiating an immune response. However, DC functions in aging have not been
      studied in detail. In this study, we have compared the innate immune functions of
      monocyte-derived myeloid DCs from elderly subjects with DCs from young
      individuals. We show that although phenotypically comparable, DCs from the aging
      are functionally different from DCs from the young. In contrast to DCs from the
      young, DCs from elderly individuals display 1) significantly reduced capacity to
      phagocytose Ags via macropinocytosis and endocytosis as determined by flow
      cytometry; 2) impaired capacity to migrate in vitro in response to the chemokines
      MIP-3beta and stromal cell-derived factor-1; and 3) significantly increased LPS
      and ssRNA-induced secretion of TNF-alpha and IL-6, as determined by ELISA.
      Investigations of intracellular signaling revealed reduced phosphorylation of AKT
      in DCs from the aging, indirectly suggesting decreased activation of the PI3K
      pathway. Because the PI3K-signaling pathway plays a positive regulatory role in
      phagocytosis and migration, and also functions as a negative regulator of TLR
      signaling by inducing activation of p38 MAPK, this may explain the aberrant
      innate immune functioning of DCs from elderly subjects. Results from real-time
      PCR and protein expression by flow cytometry demonstrated an increased expression
      of phosphatase and tensin homolog, a negative regulator of the PI3K-signaling
      pathway, in DCs from the aging. Increased phosphatase and tensin homolog may thus
      be responsible for the defect in AKT phosphorylation and, therefore, the altered
      innate immune response of DCs from elderly humans.

PMID- 17513741
TI  - Analysis of the role of bleomycin hydrolase in antigen presentation and the
      generation of CD8 T cell responses.
AB  - Long oligopeptides (>10 residues) are generated during the catabolism of cellular
      proteins in the cytosol. To be presented to T cells, such peptides must be
      trimmed by aminopeptidases to the proper size (typically 8-10 residues) to stably
      bind to MHC class I molecules. Aminopeptidases also destroy epitopes by trimming
      them to even shorter lengths. Bleomycin hydrolase (BH) is a cytosolic
      aminopeptidase that has been suggested to play a key role in generating MHC class
      I-presented peptides. We show that BH-deficient cells from mice are unimpaired in
      their ability to present epitopes from N-extended precursors or whole Ags and
      express normal levels of MHC class I molecules. Similarly, BH-deficient mice
      develop normal CD8(+) T cell responses to eight epitopes from three different
      viruses in vivo. Therefore, BH by itself is not essential for the generation or
      destruction of MHC class I peptides. In contrast, when BH(-/-) mice are crossed
      to mice lacking another cytosolic aminopeptidase, leucine aminopeptidase, the
      resulting BH(-/-)leucine aminopeptidase(-/-) progeny show a selective increase in
      CD8(+) T cell responses to the gp276 epitope from lymphocytic choriomeningitis
      virus, whereas the ability to present and respond to several other epitopes is
      unchanged. Therefore, BH does influence presentation of some Ags, although its
      role is largely redundant with other aminopeptidases.

PMID- 17513742
TI  - Human resting CD4+ T cells are constitutively inhibited by TGF beta under steady
      state conditions.
AB  - Based on studies in knockout mice, several inhibitory factors such as TGFbeta, IL
      10, or CTLA-4 have been implicated as gate keepers of adaptive immune responses.
      Lack of these inhibitory molecules leads to massive inflammatory responses mainly
      mediated by activated T cells. In humans, the integration of these inhibitory
      signals for keeping T cells at a resting state is less well understood. To
      elucidate this regulatory network, we assessed early genome-wide transcriptional
      changes during serum deprivation in human mature CD4(+) T cells. The most
      striking observation was a "TGFbeta loss signature" defined by down-regulation of
      many known TGFbeta target genes. Moreover, numerous novel TGFbeta target genes
      were identified that are under the suppressive control of TGFbeta. Expression of
      these genes was up-regulated once TGFbeta signaling was lost during serum
      deprivation and again suppressed upon TGFbeta reconstitution. Constitutive
      TGFbeta signaling was corroborated by demonstrating phosphorylated SMAD2/3 in
      resting human CD4(+) T cells in situ, which were dephosphorylated during serum
      deprivation and rephosphorylated by minute amounts of TGFbeta. Loss of TGFbeta
      signaling was particularly important for T cell proliferation induced by low
      level TCR and costimulatory signals. We suggest TGFbeta to be the most prominent
      factor actively keeping human CD4(+) T cells at a resting state.

PMID- 17513743
TI  - p300 protein acetyltransferase activity suppresses systemic lupus erythematosus
      like autoimmune disease in mice.
AB  - Conditional knock-in mice expressing a histone acetyltransferase-deficient
      version of the transcriptional coregulator p300 exclusively in B lymphocytes die
      prematurely with full penetrance. The mice develop an autoimmune disease similar
      to systemic lupus erythematosus in its pathological manifestations, such as
      splenomegaly, glomerulonephritis, vasculitis, deposition of immune complexes, and
      production of autoantibodies against dsDNA. Aged mice show a severe reduction of
      transitional and marginal zone B cells and generate aberrant mature B cells.
      These B cells show diminished proliferation in response to stimulation of the
      BCR, but respond normally to other stimuli. Yet, the mice mount a normal primary
      immune response against a T-dependent Ag. In contrast, the memory response is
      impaired. In addition, serum Ig levels, in particular IgG2b, are increased. We
      conclude that p300 acetyltransferase activity is essential for maintaining self
      tolerance of B lymphocytes. These findings support the concept of treating lupus
      with inhibitors of protein deacetylases and point to B cells as a critical target
      of these drugs.

PMID- 17513744
TI  - Functional gap junctions facilitate melanoma antigen transfer and cross
      presentation between human dendritic cells.
AB  - Previously, we found that human dendritic cells (hDCs) pulsed with a melanoma
      cell lysate (MCL) and stimulated with TNF-alpha (MCL/TNF) acquire a mature
      phenotype in vitro and are able to trigger tumor-specific immune responses when
      they are used in melanoma immunotherapy in patients. In this study, we describe
      that MCL/TNF induces gap junction (GJ)-mediated intercellular communications and
      promotes melanoma Ag transfer between ex vivo produced hDCs from melanoma
      patients. hDCs also exhibit increased expression of the GJ-related protein
      connexin 43, which contributes to GJ plaque formation after MCL/TNF stimulation.
      The addition of GJ inhibitors suppresses intercellular tumor Ag transfer between
      hDCs, thus reducing melanoma-specific T cell activation. In summary, we
      demonstrate that MCL/TNF-stimulated hDCs can establish functional GJ channels
      that participate in melanoma Ag transfer, facilitating Ag cross-presentation and
      an effective dendritic cell-mediated melanoma-specific T cell response. These
      results suggest that GJs formed between hDCs used in cancer vaccination protocols
      could be essentials for the establishment of a more efficient antitumor response.

PMID- 17513745
TI  - Parallel loss of myeloid and plasmacytoid dendritic cells from blood and lymphoid
      tissue in simian AIDS.
AB  - The loss of myeloid (mDC) and plasmacytoid dendritic cells (pDC) from the blood
      of HIV-infected individuals is associated with progressive disease. It has been
      proposed that DC loss is due to increased recruitment to lymph nodes, although
      this has not been directly tested. Similarly as in HIV-infected humans, we found
      that lineage-negative (Lin(-)) HLA-DR(+)CD11c(+)CD123(-) mDC and Lin(-)HLA
      DR(+)CD11c(-)CD123(+) pDC were lost from the blood of SIV-infected rhesus
      macaques with AIDS. In the peripheral lymph nodes of SIV-naive monkeys the
      majority of mDC were mature cells derived from skin that expressed high levels of
      HLA-DR, CD83, costimulatory molecules, and the Langerhans cell marker CD1a,
      whereas pDC expressed low levels of HLA-DR and CD40 and lacked costimulatory
      molecules, similar to pDC in blood. Surprisingly, both DC subsets were depleted
      from peripheral and mesenteric lymph nodes and spleens in monkeys with AIDS,
      although the activation status of the remaining DC subsets was similar to that of
      DC in health. In peripheral and mesenteric lymph nodes from animals with AIDS
      there was an accumulation of Lin(-)HLA-DR(moderate)CD11c(-)CD123(-) cells that
      resembled monocytoid cells but failed to acquire a DC phenotype upon culture,
      suggesting they were not DC precursors. mDC and pDC from the lymphoid tissues of
      monkeys with AIDS were prone to spontaneous death in culture, indicating that
      apoptosis may be a mechanism for their loss in disease. These findings
      demonstrate that DC are lost from rather than recruited to lymphoid tissue in
      advanced SIV infection, suggesting that systemic DC depletion plays a direct role
      in the pathophysiology of AIDS.

PMID- 17513746
TI  - Role for CD21 in the establishment of an extracellular HIV reservoir in lymphoid
      tissues.
AB  - Follicular dendritic cells (FDC) represent a major extracellular reservoir for
      HIV. A better understanding of the mechanisms of virion attachment to FDC may
      offer new avenues for reducing viral burdens in infected individuals. We used a
      murine model to investigate the establishment of extracellular HIV reservoirs in
      lymph nodes (LN). Consistent with findings in human tissues, CD21 was required
      for trapping of HIV to LN cells, as evidenced by significantly reduced virion
      binding when mice were pretreated with a C3 ligand-blocking anti-CD21 mAb and
      absence of virion trapping in CD21 knockout mice. Also consistent with findings
      in human tissues, the majority of HIV virions were associated with the FDC
      enriched fraction of LN cell preparations. Somewhat surprisingly, HIV-specific
      Abs were not essential for HIV binding to LN cells, indicating that seeding of
      the FDC reservoir may begin shortly after infection and before the development of
      HIV-specific Abs. Finally, the virion-displacing potential for anti-CD21 mAbs was
      investigated. Treatment of mice with anti-CD21 mAbs several days after injection
      of HIV significantly reduced HIV bound to LN cells. Our findings demonstrate a
      critical role for CD21 in HIV trapping by LN cells and suggest a new therapeutic
      avenue for reducing HIV reservoirs.

PMID- 17513747
TI  - CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue.
AB  - The inability of HIV-1-specific CTL to fully suppress virus replication as well
      as the failure of administration of exogenous CTL to lower viral loads are not
      understood. To evaluate the hypothesis that these phenomena are due to a failure
      of CTL to localize at sites of HIV-1 replication, we assessed the distribution of
      HIV-1 RNA and HIV-1-specific CTL identified by HIV-1 peptide/HLA class I
      tetrameric complexes (tetramers) within lymph nodes of 14 HIV-1-infected
      individuals who were not receiving antiretroviral therapy. A median of 0.04% of
      follicular compared with 0.001% of extrafollicular CD4(+) cells were estimated to
      be producing HIV-1 RNA, a 40-fold difference (p = 0.0001). Tetramer-stained cells
      were detected by flow cytometry in disaggregated lymph node cells from 11
      subjects and constituted a significantly higher fraction of CD8(+) cells in lymph
      node (mean, 2.15%) than in PBMC (mean, 1.52%; p = 0.02). In situ tetramer
      staining in three subjects' lymph nodes, in which high frequencies of tetramer
      stained cells were detected, revealed that tetramer-stained cells were primarily
      concentrated in extrafollicular regions of lymph node and were largely absent
      within lymphoid follicles. These data confirm that HIV-1-specific CTL are
      abundant within lymphoid tissues, but fail to accumulate within lymphoid
      follicles where HIV-1 replication is concentrated, suggesting that lymphoid
      follicles may be immune-privileged sites. Mechanisms underlying the exclusion of
      CTL from lymphoid follicles as well as the role of lymphoid follicles in
      perpetuating other chronic pathogens merit further investigation.

PMID- 17513748
TI  - Cytopiloyne, a polyacetylenic glucoside, prevents type 1 diabetes in nonobese
      diabetic mice.
AB  - Some polyacetylenes from the plant Bidens pilosa have been reported to treat
      diabetes. In this study, we report that the cytopiloyne from B. pilosa, which is
      structurally different from the above-mentioned polyacetylenes and inhibits
      CD4(+) T cell proliferation, effectively prevents the development of diabetes in
      nonobese diabetic mice as evidenced by a normal level of blood glucose and
      insulin and normal pancreatic islet architecture. Cytopiloyne also suppresses the
      differentiation of type 1 Th cells but promotes that of type 2 Th cells, which is
      consistent with it enhancing GATA-3 transcription. Also, long-term application of
      cytopiloyne significantly decreases the level of CD4(+) T cells inside pancreatic
      lymph nodes and spleens but does not compromise total Ab responses mediated by T
      cells. Coculture assays imply that this decrease in CD4(+) T cells involves the
      Fas ligand/Fas pathway. Overall, our results suggest that cytopiloyne prevents
      type 1 diabetes mainly via T cell regulation.

PMID- 17513749
TI  - Role of thrombospondin-1 in T cell response to ocular pigment epithelial cells.
AB  - Ocular pigment epithelium (PE) cells promote the generation of T regulators (PE
      induced Treg cells). Moreover, T cells exposed to PE acquire the capacity to
      suppress the activation of bystander T cells via TGFbeta. Membrane-bound TGFbeta
      on iris PE cells interacts with TGFbeta receptors on T cells, leading to the
      conversion of T cells to CD8(+) Treg cells via a cell contact-dependent
      mechanism. Conversely, soluble forms of TGFbeta produced by retinal PE cells can
      convert CD4(+) T cells into Treg cells in a manner that is independent of cell
      contact. In this study, we looked at the expression of immunoregulatory factors
      (TGFbeta, thrombospondins, CD59, IL-1 receptor antagonist, etc.) in PE cells as
      identified via an oligonucleotide microarray. Several thrombospondin-binding
      molecules were detected, and thus we focused subsequent analyses on
      thrombospondins. Via the conversion of latent TGFbeta to an active form that
      appears to be mediated by thrombospondin 1 (TSP-1), cultured iris PE and retinal
      PE cells induce a PE-induced Treg cell fate. After conversion, both ocular PE and
      PE-induced Treg cells express TSP-1. Regulatory T cell generation was amplified
      when the T cells also expressed TSP-1. In addition, PE-induced Treg cells
      significantly suppressed activation of bystander T cells via TSP-1. These results
      strongly suggest that the ability of ocular PE and PE-induced Treg cells to
      suppress bystander T cells depends on their capacity to produce TSP-1. Thus,
      intraocular TSP-1 produced by both ocular parenchymal cells and regulatory T
      cells is essential for immune regulation in the eye.

PMID- 17513750
TI  - In vivo signaling through the neurokinin 1 receptor favors transgene expression
      by Langerhans cells and promotes the generation of Th1- and Tc1-biased immune
      responses.
AB  - The proinflammatory capacities of the skin and the presence of high numbers of
      resident dendritic cells (DCs) constitute an ideal microenvironment for
      successful immunizations. Regardless of the ability of DCs to respond to local
      inflammatory signals in an immunostimulatory fashion, the immune functions of
      skin-resident DCs remain controversial, and epidermal Langerhans cells (LCs) have
      been referred to recently as anti-inflammatory/protolerogenic APCs. Substance P
      (SP), released by skin nerve fibers, is a potent proinflammatory neuropeptide
      that favors development of skin-associated cellular immunity. SP exerts its
      proinflammatory functions by binding with high affinity to the neurokinin 1
      receptor (NK1R). In this study, we tested whether signaling skin cells via the
      NK1R promotes humoral and cellular immunity during skin genetic immunizations. We
      used the gene gun to deliver transgenic (tg) Ag to the skin of C57BL/6 mice and
      the selective NK1R agonist [Sar(9)Met (O(2)) (11)]-SP as a potential
      proinflammatory Th1-biasing adjuvant. Our strategy expressed tg Ag exclusively in
      the epidermis and induced a preferential migration of activated LCs to skin
      draining lymph nodes. Local administration of the NK1R agonist during skin
      genetic immunizations increased significantly the expression of tg Ag by a
      mechanism involving the translocation of NF-kappaB into the nuclei of cutaneous
      DCs homing to skin-draining lymph nodes. Importantly, our immunization approach
      resulted in Th1 and T cytotoxic (CTL)-1 bias of effector T cells that supported
      cellular and Ab-mediated immune responses. We demonstrate that signaling skin
      cells via the NK1R provides the adjuvant effect which favors the
      immunostimulatory functions of LCs.

PMID- 17513751
TI  - Rapamycin-conditioned dendritic cells are poor stimulators of allogeneic CD4+ T
      cells, but enrich for antigen-specific Foxp3+ T regulatory cells and promote
      organ transplant tolerance.
AB  - The ability of dendritic cells (DC) to regulate Ag-specific immune responses via
      their influence on T regulatory cells (Treg) may be key to their potential as
      therapeutic tools or targets for the promotion/restoration of tolerance. In this
      report, we describe the ability of maturation-resistant, rapamycin (RAPA)
      conditioned DC, which are markedly impaired in Foxp3(-) T cell allostimulatory
      capacity, to favor the stimulation of murine alloantigen-specific
      CD4(+)CD25(+)Foxp3(+) Treg. This was distinct from control DC, especially
      following CD40 ligation, which potently expanded non-Treg. RAPA-DC-stimulated
      Treg were superior alloantigen-specific suppressors of T effector responses
      compared with those stimulated by control DC. Supporting the ability of RAPA to
      target effector T and B cells, but permit the proliferation and suppressive
      function of Treg, an infusion of recipient-derived alloantigen-pulsed RAPA-DC
      followed by a short postoperative course of low-dose RAPA promoted indefinite
      (>100 day) heart graft survival. This was associated with graft infiltration by
      CD4(+)Foxp3(+) Treg and the absence of transplant vasculopathy. The adoptive
      transfer of CD4(+) T cells from animals with long-surviving grafts conferred
      resistance to rejection. These novel findings demonstrate that, whereas
      maturation resistance does not impair the capacity of RAPA-DC to modulate Treg,
      it profoundly impairs their ability to expand T effector cells. A demonstration
      of this mechanism endorses their potential as tolerance-promoting cellular
      vaccines.

PMID- 17513752
TI  - Adaptation of TCR repertoires to self-peptides in regulatory and nonregulatory
      CD4+ T cells.
AB  - Currently, it is not understood how the specificity of the TCR guides CD4(+) T
      cells into the conventional lineage (Tconv) vs directing them to become
      regulatory (Treg) cells defined by the Foxp3 transcription factor. To address
      this question, we made use of the "Limited" (LTD) mouse, which has a restricted
      TCR repertoire with a fixed TCRbeta chain and a TCRalpha chain minilocus. The TCR
      repertoires of Tconv and Treg cells were equally broad, were distinct, yet
      overlapped significantly, representing a less strict partition than previously
      seen between CD4 and CD8 T cells. As a group, the CDR3alpha motifs showed a
      significant trend to higher positive charge in Treg than in Tconv cells. The
      Tconv and Treg repertoires were both reshaped between thymus and periphery.
      Reducing the array of peptides presented by MHC class II molecules by introducing
      the H2-DM(o/o) mutation into the LTD mouse led to parallel shifts in the
      repertoires of Tconv and Treg cells. In both cases, the CDR3alpha elements were
      entirely different and strikingly shortened, relative to normal LTD mice. These
      peculiar sequences conferred reactivity to wild-type MHC class II complexes and
      were excluded from the normal repertoire, even among Treg cells, indicating that
      some forms of self-reactivity are incompatible with selection into the Treg
      lineage. In conclusion, the Treg repertoire is broad, with distinct composition
      and characteristics, yet significantly overlapping and sharing structural
      constraints with the repertoire of conventional CD4(+) T cells.

PMID- 17513753
TI  - Impaired mast cell maturation and degranulation and attenuated allergic responses
      in Ndrg1-deficient mice.
AB  - We have previously reported that N-myc downstream regulated gene-1 (NDRG1) is an
      early inducible protein during the maturation of mouse bone marrow-derived mast
      cells (BMMCs) toward a connective tissue mast cell-like phenotype. To clarify the
      function of NDRG1 in mast cells and allergic responses, we herein analyzed mast
      cell-associated phenotypes of mice lacking the Ndrg1 gene. Allergic responses
      including IgE-mediated passive systemic and cutaneous anaphylactic reactions were
      markedly attenuated in Ndrg1-deficient mice as compared with those in wild-type
      mice. In Ndrg1-deficient mice, dermal and peritoneal mast cells were decreased in
      number and morphologically abnormal with impaired degranulating ability. Ex vivo,
      Ndrg1-deficient BMMCs cocultured with Swiss 3T3 fibroblasts in the presence of
      stem cell factor, a condition that facilitates the maturation of BMMCs toward a
      CTMC-like phenotype, displayed less exocytosis than replicate wild-type cells
      after the cross-linking of FcepsilonRI or stimulation with compound 48/80, even
      though the exocytotic response of IL-3-maintained, immature BMMCs from both
      genotypes was comparable. Unlike degranulation, the production of leukotriene and
      cytokines by cocultured BMMCs was unaffected by NDRG1 deficiency. Taken together,
      the altered phenotypes of Ndrg1-deficient mast cells both in vivo and ex vivo
      suggest that NDRG1 has roles in the terminal maturation and effector function
      (degranulation) of mast cells.

PMID- 17513754
TI  - Plasmodium berghei-infected primary hepatocytes process and present the
      circumsporozoite protein to specific CD8+ T cells in vitro.
AB  - A substantial and protective response against malaria liver stages is directed
      against the circumsporozoite protein (CSP) and involves induction of CD8(+) T
      cells and production of IFN-gamma. CSP-derived peptides have been shown to be
      presented on the surface of infected hepatocytes in the context of MHC class I
      molecules. However, little is known about how the CSP and other sporozoite Ags
      are processed and presented to CD8(+) T cells. We investigated how primary
      hepatocytes from BALB/c mice process the CSP of Plasmodium berghei after live
      sporozoite infection and present CSP-derived peptides to specific H-2K(d)
      restricted CD8(+) T cells in vitro. Using both wild-type and spect(-/-) P.
      berghei sporozoites, we show that both infected and traversed primary hepatocytes
      process and present the CSP. The processing and presentation pathway was found to
      involve the proteasome, Ag transport through a postendoplasmic reticulum
      compartment, and aspartic proteases. Thus, it can be hypothesized that infected
      hepatocytes can contribute in vivo to the elicitation and expansion of a T cell
      response.

PMID- 17513755
TI  - The tick salivary protein, Salp15, inhibits the development of experimental
      asthma.
AB  - Activation of Th2 CD4(+) T cells is necessary and sufficient to elicit allergic
      airway disease, a mouse model with many features of human allergic asthma.
      Effectively controlling the activities of these cells could be a panacea for
      asthma therapy. Blood-feeding parasites have devised remarkable strategies to
      effectively evade the immune response. For example, ticks such as Ixodes
      scapularis, which must remain on the host for up to 7 days to feed to repletion,
      secrete immunosuppressive proteins. Included among these proteins is the 15-kDa
      salivary protein Salp15, which inhibits T cell activation and IL-2 production.
      Our objective for these studies was to evaluate the T cell inhibitory properties
      of Salp15 in a mouse model of allergic asthma. BALB/cJ mice were Ag sensitized by
      i.p. injection of OVA in aluminum hydroxide, with or without 50 mug of Salp15, on
      days 0 and 7. All mice were challenged with aerosolized OVA on days 14-16 and
      were studied on day 18. Compared with control mice sensitized with Ag, mice
      sensitized with Ag and Salp15 displayed significantly reduced airway
      hyperresponsiveness, eosinophilia, Ag-specific IgG1 and IgE, mucus cell
      metaplasia, and Th2 cytokine secretion in vivo and by CD4(+) T cells restimulated
      with Ag in vitro. Our results demonstrate that Salp15 can effectively prevent the
      generation of a Th2 immune response and the development of experimental asthma.
      These studies, and those of others, support the notion that a lack of
      ectoparasitism may contribute to the increasing prevalence of allergic asthma.

PMID- 17513756
TI  - C57BL/6 mice genetically deficient in IL-12/IL-23 and IFN-gamma are susceptible
      to experimental autoimmune myasthenia gravis, suggesting a pathogenic role of non
      Th1 cells.
AB  - Immunization with Torpedo acetylcholine receptor (TAChR) induces experimental
      autoimmune myasthenia gravis (EAMG) in C57BL/6 (B6) mice. EAMG development needs
      IL-12, which drives differentiation of Th1 cells. The role of IFN-gamma, an
      important Th1 effector, is not clear and that of IL-17, a proinflammatory
      cytokine produced by Th17 cells, is unknown. In this study, we examined the
      effect of simultaneous absence of IL-12 and IFN-gamma on EAMG susceptibility,
      using null mutant B6 mice for the genes of both the IL-12/IL-23 p40 subunit and
      IFN-gamma (dKO mice). Wild-type (WT) B6 mice served as control for EAMG
      induction. All mice were immunized with TAChR in Freund's adjuvant. dKO mice
      developed weaker anti-TAChR CD4(+)T cells and Ab responses than WT mice. Yet,
      they developed EAMG symptoms, anti-mouse acetylcholine receptor (AChR) Ab, and
      CD4(+) T cell responses against mouse AChR sequences similar to those of WT mice.
      dKO and WT mice had similarly reduced AChR content in their muscles, and IgG and
      complement at the neuromuscular junction. Naive dKO mice had significantly fewer
      NK, NKT, and CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells than naive WT mice.
      Treg cells from TAChR-immunized dKO mice had significantly less suppressive
      activity in vitro than Treg cells from TAChR-immunized WT mice. In contrast,
      TAChR-specific CD4(+) T cells from TAChR-immunized dKO and WT mice secreted
      comparable amounts of IL-17 after stimulation in vitro with TAChR. The
      susceptibility of dKO mice to EAMG may be due to reduced Treg function, in the
      presence of a normal function of pathogenic Th17 cells.

PMID- 17513757
TI  - Interaction of PRP4 with Kruppel-like factor 13 regulates CCL5 transcription.
AB  - Activation of resting T lymphocytes initiates differentiation into mature
      effector cells over 3-7 days. The chemokine CCL5 (RANTES) and its major
      transcriptional regulator, Kruppel-like factor 13 (KLF13), are expressed late (3
      5 days) after activation in T lymphocytes. Using yeast two-hybrid screening of a
      human thymus cDNA library, PRP4, a serine/threonine protein kinase, was
      identified as a KLF13-binding protein. Specific interaction of KLF13 and PRP4 was
      confirmed by reciprocal coimmunoprecipitation. PRP4 is expressed in PHA
      stimulated human T lymphocytes from days 1 and 7 with a peak at day 3. Using an
      in vitro kinase assay, it was found that PRP4 phosphorylates KLF13. Furthermore,
      although phosphorylation of KLF13 by PRP4 results in lower binding affinity to
      the A/B site of the CCL5 promoter, coexpression of PRP4 and KLF13 increases
      nuclear localization of KLF13 and CCL5 transcription. Finally, knock-down of PRP4
      by small interfering RNA markedly decreases CCL5 expression in T lymphocytes.
      Thus, PRP4-mediated phosphorylation of KLF13 plays a role in the regulation of
      CCL5 expression in T lymphocytes.

PMID- 17513758
TI  - Down-regulation of the SWI/SNF chromatin remodeling activity by TCR signaling is
      required for proper thymocyte maturation.
AB  - The process of thymocyte development requires an exquisite regulation of many
      genes via transcription factors and chromatin remodeling activities. Even though
      the SWI/SNF chromatin remodeling complex has been thought to play important roles
      during thymocyte development, its known function is very limited. In this study,
      we show that the SWI/SNF chromatin remodeling activity is finely regulated during
      thymocyte maturation process, especially during thymocyte selections. We found
      that TCR signaling directly down-regulates mBRG1 and SWI3-related gene, the core
      components of murine SWI/SNF complex, during thymocyte maturation. Constitutive
      expression of SWI3-related gene in developing thymocytes attenuated the down
      regulation of the SWI/SNF complex and resulted in a change in the expression of
      genes such as linker for activation of T cells and casitas B lineage lymphoma,
      which affected the TCR-mediated intracellular signaling pathway. The defects in
      TCR signaling resulted in the disruption of both positive and negative selections
      in specific TCR transgenic mice systems. Our results state, for the first time,
      that the chromatin remodeling activity needs to be finely controlled for proper
      thymocyte selection and maturation processes.

PMID- 17513759
TI  - Genome-wide analysis of gene expression in T cells to identify targets of the NF
      kappa B transcription factor c-Rel.
AB  - It is well established that the NF-kappaB family of transcription factors serves
      a major role in controlling gene expression in response to T cell activation, but
      the genome-wide roles of individual family members remain to be determined. c
      Rel, a member of the NF-kappaB family, appears to play a specific role in T cell
      function because T cells from c-Rel(-/-) animals are defective in their response
      to immune signals. We have used expression profiling to identify sets of genes
      that are affected by either deletion or overexpression of c-Rel in T cells. Very
      few of these genes exhibit a strong requirement for c-Rel; rather, c-Rel appears
      to modulate the expression of a large number of genes in these cells. The sets of
      c-Rel-affected genes are significantly enriched for genes containing consensus NF
      kappaB/Rel sites in their proximal promoter regions. In addition, their promoters
      contain a higher average density of NF-kappaB/Rel sites compared with all genes
      represented on the microarrays. A transcriptional module comprised of two closely
      spaced c-Rel consensus sites is found with higher frequency in the c-Rel-affected
      gene sets and may represent an important control module for genes regulated by c
      Rel or other NF-kappaB family members. We confirmed the importance of these
      findings on a subgroup of genes by using quantitative PCR to monitor gene
      expression as well as in vitro c-Rel/DNA binding assays and luciferase reporter
      assays. The c-Rel-regulated genes identified here support a role for c-Rel in
      inflammatory responses as well as in the promotion of cell growth and survival.

PMID- 17513760
TI  - The central leucine-rich repeat region of chicken TLR16 dictates unique ligand
      specificity and species-specific interaction with TLR2.
AB  - The ligand specificity of human TLR (hTLR) 2 is determined through the formation
      of functional heterodimers with either hTLR1 or hTLR6. The chicken carries two
      TLR (chTLR) 2 isoforms, type 1 and type 2 (chTLR2t1 and chTLR2t2), and one
      putative TLR1/6/10 homologue (chTLR16) of unknown function. In this study, we
      report that transfection of HeLa cells with the various chicken receptors yields
      potent NF-kappaB activation for the receptor combination of chTLR2t2 and chTLR16
      only. The sensitivity of this complex was strongly enhanced by human CD14. The
      functional chTLR16/chTLR2t2 complex responded toward both the hTLR2/6-specific
      diacylated peptide S-(2,3-bispalmitoyloxypropyl)-Cys-Gly-Asp-Pro-Lys-His-Pro-Lys
      Ser-Phe (FSL-1) and the hTLR2/1 specific triacylated peptide tripalmitoyl-S
      (bis(palmitoyloxy)propyl)-Cys-Ser-(Lys)(3)-Lys (Pam(3)CSK(4)), indicating that
      chTLR16 covers the functions of both mammalian TLR1 and TLR6. Dissection of the
      species specificity of TLR2 and its coreceptors showed functional chTLR16 complex
      formation with chTLR2t2 but not hTLR2. Conversely, chTLR2t2 did not function in
      combination with hTLR1 or hTLR6. The use of constructed chimeric receptors in
      which the defined domains of chTLR16 and hTLR1 or hTLR6 had been exchanged
      revealed that the transfer of leucine-rich repeats (LRR) 6-16 of chTLR16 into
      hTLR6 was sufficient to confer dual ligand specificity to the human receptor and
      to establish species-specific interaction with chTLR2t2. Collectively, our data
      indicate that diversification of the central LRR region of the TLR2 coreceptors
      during evolution has put constraints on both their ligand specificity and their
      ability to form functional complexes with TLR2.

PMID- 17513761
TI  - Novel engineered trastuzumab conformational epitopes demonstrate in vitro and in
      vivo antitumor properties against HER-2/neu.
AB  - Trastuzumab is a growth-inhibitory humanized Ab targeting the oncogenic protein
      HER-2/neu. Although trastuzumab is approved for treatment of advanced breast
      cancer, a number of concerns exist with passive immunotherapy. Treatment is
      expensive and has a limited duration of action, necessitating repeated
      administrations of the mAb. Active immunotherapy with conformational B cell
      epitopes affords the possibility of generating an enduring immune response,
      eliciting protein-reactive high-affinity anti-peptide Abs. The three-dimensional
      structure of human HER-2 in complex with trastuzumab reveals that the Ag-binding
      region of HER-2 spans residues 563-626 that comprises an extensive disulfide
      bonding pattern. To delineate the binding region of HER-2, we have designed four
      synthetic peptides with different levels of conformational flexibility. Chimeric
      peptides incorporating the measles virus fusion "promiscuous" T cell epitope via
      a four-residue linker sequence were synthesized, purified, and characterized. All
      conformational peptides were recognized by trastuzumab and prevented the function
      of trastuzumab inhibiting tumor cell proliferation, with 563-598 and 597-626
      showing greater reactivity. All epitopes were immunogenic in FVB/N mice with Abs
      against 597-626 and 613-626 recognizing HER-2. The 597-626 epitope was
      immunogenic in outbred rabbits eliciting Abs which recognized HER-2, competed
      with trastuzumab for the same epitope, inhibited proliferation of HER-2
      expressing breast cancer cells in vitro and caused their Ab-dependent cell
      mediated cytotoxicity. Moreover, immunization with the 597-626 epitope
      significantly reduced tumor burden in transgenic BALB-neuT mice. These results
      suggest the peptide B cell immunogen is appropriate as a vaccine for HER-2
      overexpressing cancers because the resulting Abs show analogous biological
      properties to trastuzumab.

PMID- 17513762
TI  - The neutralization properties of a HIV-specific antibody are markedly altered by
      glycosylation events outside the antigen-binding domain.
AB  - Neutralizing Abs constitute a pivotal mechanism of the adaptive immune response
      against HIV-1 infection. Yet, most of the Abs that appear in the circulation
      during HIV infection are nonneutralizing. In this study, we report a dramatic
      change of the neutralizing properties of a human Ab reactive with the
      nonneutralizing epitope termed cluster I on the HIV-1 transmembrane protein gp41
      when the Ab was produced in Chinese hamster ovary (CHO)-K1 cells. Our laboratory
      has previously reported that the Ab F240, when produced in a hybridoma, is
      nonneutralizing as assessed by standard neutralization assays. The F240 IgG1 Ab
      expressed in CHO cells acquired a strong neutralization activity against a broad
      range of HIV isolates without a change in immunoreactivity. Sequencing of the
      F240 mRNAs produced in the parental hybridoma and CHO cells revealed identical
      sequences, suggesting that acquired neutralization resulted from cell-specific
      posttranslational modifications. We found that the Ab produced by CHO cells is
      glycosylated to a greater extent than the parental Ab produced by the hybridoma.
      Moreover, treatment with peptide N-glycosidase F abrogated F240 neutralization,
      in an isolate-specific manner, but not Ab b12 neutralization. Interestingly, the
      F240 isotype-switched variants IgG3 and IgG4, also expressed in CHO cells,
      exhibited identical immunoreactivity to IgG1 isotypes but had clear differences
      in viral neutralization. These results suggest that structural features of the Ig
      molecule other than the primary sequence of the variable regions play a more
      prominent role in HIV neutralization than anticipated.

PMID- 17513763
TI  - Defining in vivo transcription factor complexes of the murine CD21 and CD23
      genes.
AB  - The expression of the CD21 and CD23 genes is coincident with differentiation from
      transition 1 B cells (T1) to transition 2 B cells (T2). To define constituents
      controlling CD21 and CD23 expression, we conducted chromatin immunoprecipitation
      analyses for candidate transcription factors. We found constitutive binding of
      Oct-1, NFAT species, YY1, NF-kappaB-p52, Pax5, E2A, and RBP-Jkappa to CD21
      sequences and NF-kappaB-p52, Pax5, NFAT species, E2A, and RBP-Jkappa to CD23
      promoter sequences. Splenic T and B cell subsets displayed constitutive binding
      of YY1, NF-kappaB-p52, Pax5, and Oct-1 proteins to CD21 sequences in B cells but
      no specific binding of NFATc3 or Pax5 in T cells. Similarly, CD23 sequences
      demonstrated constitutive binding of NF-kappaB-p52 in splenic T and B cells but
      only Pax5 in B cells. Of the various NFAT species, only a subset were found
      forming constitutive DNA/protein complexes with the CD21, CD23, and IL-2 gene
      sequences. Maturing B cells in the marrow possess stable Pax5 complexes on CD19,
      CD21, and CD23 gene promoters in the nuclei of such cells, even though only CD19
      is expressed. The similarity of genetic controlling elements between the CD21 and
      CD23 genes does not suggest a mechanism for alternative regulation of these
      genes; however, separation of splenic B cell subsets into T1, T2, marginal zone
      (MZ), and mature follicular B cells, followed by quantitative RT-PCR,
      demonstrated the lack of appreciable CD23 transcripts in CD21(+) MZ cells. We
      propose an alternative derivation of MZ cells as maturing directly from T1 cells,
      leaving CD23 transcriptionally inactive in that lineage of cells.

PMID- 17513764
TI  - Genomics and diversity of the common marmoset monkey NK complex.
AB  - The common marmoset monkey (Callithrix jacchus) is a New World primate that is
      increasingly used in biomedical research as a model organism. Due to the
      occurrence of natural bone marrow chimerism, it represents a particularly useful
      primate model in immunological research. In this study, we describe the genomic
      organization of the CD94, NKG2, and LY49L genes in the NK complex (NKC) of the
      common marmoset based on complete sequencing of a bacterial artificial chromosome
      clonal contig. This region of the marmoset NKC is 1.5 times smaller than its
      human counterpart, but the genes are colinear and orthologous. One exception is
      the activating NKG2CE gene, which is probably an ancestral form of the NKG2C- and
      NKG2E-activating receptor genes of humans and great apes. The two completely
      sequenced marmoset bacterial artificial chromosome clones are derived from
      distinct haplotypes, which differ by 200 sites in the overlapping sequence.
      Analyses of NKC genes in nine additional marmoset individuals revealed a moderate
      degree of polymorphism of the CD94, NKG2A, NKG2CE, and NKG2D genes. Furthermore,
      expression analyses identified several alternatively spliced transcripts,
      particularly of the CD94 gene. Several products of alternative splicing of NKC
      genes are highly conserved among primates. Alternative transcriptional start
      sites were found, but these probably do not lead to a change of the translational
      start site or result in longer or shorter cytoplasmic regions of these type II
      membrane receptors.

PMID- 17513765
TI  - Extended gene map reveals tripartite motif, C-type lectin, and Ig superfamily
      type genes within a subregion of the chicken MHC-B affecting infectious disease.
AB  - MHC haplotypes have a remarkable influence on whether tumors form following
      infection of chickens with oncogenic Marek's disease herpesvirus. Although
      resistance to tumor formation has been mapped to a subregion of the chicken MHC-B
      region, the gene or genes responsible have not been identified. A full gene map
      of the subregion has been lacking. We have expanded the MHC-B region gene map
      beyond the 92-kb core previously reported for another haplotype revealing the
      presence of 46 genes within 242 kb in the Red Jungle Fowl haplotype. Even though
      MHC-B is structured differently, many of the newly revealed genes are related to
      loci typical of the MHC in other species. Other MHC-B loci are homologs of genes
      found within MHC paralogous regions (regions thought to be derived from ancient
      duplications of a primordial immune defense complex where genes have undergone
      differential silencing over evolutionary time) on other chromosomes. Still others
      are similar to genes that define the NK complex in mammals. Many of the newly
      mapped genes display allelic variability and fall within the MHC-B subregion
      previously shown to affect the formation of Marek's disease tumors and hence are
      candidates for genes conferring resistance.

PMID- 17513766
TI  - The autoimmune regulator directly controls the expression of genes critical for
      thymic epithelial function.
AB  - The autoimmune regulator (Aire) gene plays an essential role in negative
      selection of T cells and deletion of autoreactive T cells in the thymus. The
      defect in thymic selection in Aire(-/-) mice was attributed to the repressed
      expression of tissue-specific Ags in the thymic epithelial cells and defective Ag
      presentation; however, the molecular mechanism underlying these functions has
      been elusive. Using the chromatin immunoprecipitation technique, we demonstrate
      here that Aire binds in vivo to specific DNA sequence motifs and directly
      regulates thymic expression of genes important for thymic functions including
      expression of autoantigens, cytokines, transcription factors, and
      posttranslational modifiers. These results unambiguously established Aire as a
      key transcriptional regulator of the immune system.

PMID- 17513767
TI  - Cooperativity of hydrophobic anchor interactions: evidence for epitope selection
      by MHC class II as a folding process.
AB  - Peptide binding to MHC class II (MHCII) molecules is stabilized by hydrophobic
      anchoring and hydrogen bond formation. We view peptide binding as a process in
      which the peptide folds into the binding groove and to some extent the groove
      folds around the peptide. Our previous observation of cooperativity when
      analyzing binding properties of peptides modified at side chains with medium to
      high solvent accessibility is compatible with such a view. However, a large
      component of peptide binding is mediated by residues with strong hydrophobic
      interactions that bind to their respective pockets. If these reflect initial
      nucleation events they may be upstream of the folding process and not show
      cooperativity. To test whether the folding hypothesis extends to these anchor
      interactions, we measured dissociation and affinity to HLA-DR1 of an influenza
      hemagglutinin-derived peptide with multiple substitutions at major anchor
      residues. Our results show both negative and positive cooperative effects between
      hydrophobic pocket interactions. Cooperativity was also observed between
      hydrophobic pockets and positions with intermediate solvent accessibility,
      indicating that hydrophobic interactions participate in the overall folding
      process. These findings point out that predicting the binding potential of
      epitopes cannot assume additive and independent contributions of the interactions
      between major MHCII pockets and corresponding peptide side chains.

PMID- 17513768
TI  - IFN-gamma- and TNF-independent vitamin D-inducible human suppression of
      mycobacteria: the role of cathelicidin LL-37.
AB  - Vitamin D deficiency is associated with susceptibility to tuberculosis, and its
      biologically active metabolite, 1alpha,25 dihydroxyvitamin D(3)
      (1alpha,25(OH)(2)D(3)), has pleiotropic immune effects. The mechanisms by which
      1alpha,25(OH)(2)D(3) protects against tuberculosis are incompletely understood.
      1alpha,25(OH)(2)D(3) reduced the growth of mycobacteria in infected human PBMC
      cultures in a dose-dependent fashion. Coculture with agonists or antagonists of
      the membrane or nuclear vitamin D receptors indicated that these effects were
      primarily mediated by the nuclear vitamin D receptors. 1alpha,25(OH)(2)D(3)
      reduced transcription and secretion of protective IFN-gamma, IL-12p40, and TNF in
      infected PBMC and macrophages, indicating that 1alpha,25(OH)(2)D(3) does not
      mediate protection via these cytokines. Although NOS2A was up-regulated by
      1alpha,25(OH)(2)D(3), inhibition of NO formation marginally affected the
      suppressive effect of 1alpha,25(OH)(2)D(3) on bacillus Calmette Guerin in
      infected cells. By contrast, 1alpha,25(OH)(2)D(3) strongly up-regulated the
      cathelicidin hCAP-18 gene, and some hCAP-18 polypeptide colocalized with CD14 in
      1alpha,25(OH)(2)D(3) stimulated PBMC, although no detectable LL-37 peptide was
      found in supernatants from similar 1alpha,25(OH)(2)D(3)-stimulated PBMC cultures.
      A total of 200 mug/ml of the active peptide LL-37, in turn, reduced the growth of
      Mycobacterium tuberculosis in culture by 75.7%. These findings suggest that
      vitamin D contributes to protection against TB by "nonclassical" mechanisms that
      include the induction of antimicrobial peptides.

PMID- 17513769
TI  - Tubulation of class II MHC compartments is microtubule dependent and involves
      multiple endolysosomal membrane proteins in primary dendritic cells.
AB  - Immature dendritic cells (DCs) capture exogenous Ags in the periphery for
      eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs
      deliver peptide-loaded class II MHC molecules from these compartments to the cell
      surface via long tubular structures (endolysosomal tubules). The nature and rules
      that govern the movement of these DC compartments are unknown. In this study, we
      demonstrate that the tubules contain multiple proteins including the class II MHC
      molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82,
      members of the tetraspanin family. Endolysosomal tubules can be stained with
      acidotropic dyes, indicating that they are extensions of lysosomes. However, the
      proper trafficking of class II MHC molecules themselves is not necessary for
      endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal
      tubules, demonstrating that MyD88-dependent TLR activation is not necessary for
      the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic
      and saltatory movement, including bidirectional travel. Measured velocities are
      consistent with motor-based movement along microtubules. Indeed, nocodazole
      causes the collapse of endolysosomal tubules. In addition to its association with
      microtubules, endolysosomal tubules follow the plus ends of microtubules as
      visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP.

PMID- 17513770
TI  - A novel functional CTL avidity/activity compartmentalization to the site of
      mucosal immunization contributes to protection of macaques against simian/human
      immunodeficiency viral depletion of mucosal CD4+ T cells.
AB  - The presence of high-avidity CTLs in the right compartment can greatly affect
      clearance of a virus infection (for example, AIDS viral infection of and
      dissemination from mucosa). Comparing mucosal vs systemic immunization, we
      observed a novel compartmentalization of CTL avidity and proportion of
      functionally active Ag-specific CD8(+) T cells to tissues proximal to sites of
      immunization. Whereas both s.c. and intrarectal routes of immunization induced
      tetramer(+) cells in the spleen and gut, the mucosal vaccine induced a higher
      percentage of functioning IFN-gamma(+) Ag-specific CD8(+) T cells in the gut
      mucosa in mice. Translating to the CD8(+) CTL avidity distribution in rhesus
      macaques, intrarectal vaccination induced more high-avidity mucosal CTL than s.c.
      vaccination and protection of mucosal CD4(+) T cells from AIDS viral depletion,
      whereas systemic immunization induced higher avidity IFN-gamma-secreting cells in
      the draining lymph nodes but no protection of mucosal CD4(+) T cells, after
      mucosal challenge with pathogenic simian/human immunodeficiency virus. Mucosal
      CD4(+) T cell loss is an early critical step in AIDS pathogenesis. The
      preservation of CD4(+) T cells in colonic lamina propria and the reduction of
      virus in the intestine correlated better with high-avidity mucosal CTL induced by
      the mucosal AIDS vaccine. This preferential localization of high-avidity CTL may
      explain previous differences in vaccination results and may guide future
      vaccination strategy.

PMID- 17513771
TI  - B cells moderate inflammatory progression and enhance bacterial containment upon
      pulmonary challenge with Mycobacterium tuberculosis.
AB  - Though much is known about the function of T lymphocytes in the adaptive immune
      response against Mycobacterium tuberculosis, comparably little is understood
      regarding the corresponding role of B lymphocytes. Indicating B cells as
      components of lymphoid neogenesis during pulmonary tuberculosis, we have
      identified ectopic germinal centers (GCs) in the lungs of infected mice. B cells
      in these pulmonary lymphoid aggregates express peanut agglutinin and GL7, two
      markers of GC B cells, as well as CXCR5, and migrate in response to the lymphoid
      associated chemokine CXCL13 ex vivo. CXCL13 is negatively regulated by the
      presence of B cells, as its production is elevated in lungs of B cell-deficient
      (B cell(-/-)) mice. Upon aerosol with 100 CFU of M. tuberculosis Erdman, B cell(
      /-) mice have exacerbated immunopathology corresponding with elevated pulmonary
      recruitment of neutrophils. Infected B cell(-/-) mice show increased production
      of IL-10 in the lungs, whereas IFN-gamma, TNF-alpha, and IL-10R remain unchanged
      from wild type. B cell(-/-) mice have enhanced susceptibility to infection when
      aerogenically challenged with 300 CFU of M. tuberculosis corresponding with
      elevated bacterial burden in the lungs but not in the spleen or liver. Adoptive
      transfer of B cells complements the phenotypes of B cell(-/-) mice, confirming a
      role for B cells in both modulation of the host response and optimal containment
      of the tubercle bacillus. As components of ectopic GCs, moderators of
      inflammatory progression, and enhancers of local immunity against bacterial
      challenge, B cells may have a greater role in the host defense against M.
      tuberculosis than previously thought.

PMID- 17513772
TI  - Viral interference with antigen presentation does not alter acute or chronic CD8
      T cell immunodominance in murine cytomegalovirus infection.
AB  - Both human CMV and murine CMV (MCMV) elicit large CD8 T cell responses, despite
      the potent effects of viral genes that interfere with the MHC class I (MHC I)
      pathway of Ag presentation. To investigate the impact of immune evasion on CD8 T
      cell priming, we infected mice with wild-type (wt) MCMV or a mutant lacking its
      MHC I immune evasion genes, Deltam4+m6+m152 MCMV. In acute infection, the two
      viruses elicited a CD8 T cell response to 26 peptide epitopes that was virtually
      identical in total size, kinetics, and immunodominance hierarchy. This occurred
      despite results demonstrating that primary DCs are susceptible to the effects of
      MCMV's MHC I immune evasion genes. Eight months later, responses to both wt and
      mutant MCMV displayed the same CD8 T cell "memory inflation" and altered
      immunodominance that characterize the transition to chronic MCMV infection in
      C57BL/6 mice. Taken together, these findings suggest either that cross-priming
      dominates over direct CD8 T cell priming in both acute and chronic MCMV
      infection, or else that the MHC I immune evasion genes of MCMV are unable to
      alter direct CD8 T cell priming in vivo. At 2 years postinfection, differences in
      CD8 T cell immunodominance emerged between individual mice, but on average there
      were only slight differences between wt and mutant virus infections. Overall, the
      data indicate that the presence or absence of MHC I immune evasion genes has
      remarkably little impact on the size or specificity of the MCMV-specific CD8 T
      cell response over an entire lifetime of infection.

PMID- 17513773
TI  - Biphasic effect of gingipains from Porphyromonas gingivalis on the human
      complement system.
AB  - Periodontitis is an inflammatory disease of the supporting structures of the
      teeth and is caused by, among other agents, Porphyromonas gingivalis. P.
      gingivalis is very resistant to killing by human complement, which is present in
      a gingival fluid at 70% of the serum concentration. We found that the incubation
      of human serum with purified cysteine proteases of P. gingivalis (gingipains) or
      P. gingivalis wild-type strains W83 and W50 resulted in a drastic decrease of the
      bactericidal activity of the serum. In contrast, serum treated with P. gingivalis
      mutants lacking gingipains (particularly strains without HRgpA) maintained
      significant bactericidal activity. To understand in detail the mechanism by which
      gingipains destroy the serum bactericidal activity, we investigated the effects
      of gingipains on the human complement system. We found that all three proteases
      degraded multiple complement components, with arginine-specific gingipains (HRgpA
      and RgpB) being more efficient than lysine-specific gingipain (Kgp).
      Interestingly, all three proteases at certain concentrations were able to
      activate the C1 complex in serum, which resulted in the deposition of C1q on
      inert surfaces and on bacteria themselves. It is therefore plausible that P.
      gingivalis activates complement when present at low numbers, resulting in a local
      inflammatory reaction and providing the bacteria with a colonization opportunity
      and nutrients. At later stages of infection the concentration of proteases is
      high enough to destroy complement factors and thus render the bacteria resistant
      to the bactericidal activity of complement.

PMID- 17513774
TI  - Dendritic cell-derived IL-12p40 homodimer contributes to susceptibility in
      cutaneous leishmaniasis in BALB/c mice.
AB  - Protection against Leishmania major in resistant C57BL/6 mice is mediated by Th1
      cells, whereas susceptibility in BALB/c mice is the result of Th2 development. IL
      12 release by L. major-infected dendritic cells (DC) is critically involved in
      differentiation of Th1 cells. Previously, we reported that strain differences in
      the production of DC-derived factors, e.g., IL-1alphabeta, are in part
      responsible for disparate disease outcome. In the present study, we analyzed the
      release of IL-12 from DC in more detail. Stimulated DC from C57BL/6 and BALB/c
      mice released comparable amounts of IL-12p40 and p70. In the absence of IL-4,
      BALB/c DC produced significantly more IL-12p40 than C57BL/6 DC. Detailed analyses
      by Western blot and ELISA revealed that one-tenth of IL-12p40 detected in DC
      supernatants was released as the IL-12 antagonist IL-12p40 homodimer (IL-12p80).
      BALB/c DC released approximately 2-fold more IL-12p80 than C57BL/6 DC both in
      vitro and in vivo. Local injection of IL-12p80 during the first 3 days after
      infection resulted in increased lesion volumes for several weeks in both L. major
      infected BALB/c or C57BL/6 mice, in higher lesional parasite burdens, and
      decreased Th1-cytokine production. Finally, IL-12p40-transgenic C57BL/6 mice
      characterized by overexpression of p40 showed increased levels of serum IL-12p80
      and enhanced disease susceptibility. Thus, in addition to IL-1alphabeta, strain
      dependent differences in the release of other DC-derived factors such as IL-12p80
      may influence genetically determined disease outcome.

PMID- 17513775
TI  - STAT1 expression in dendritic cells, but not T cells, is required for immunity to
      Leishmania major.
AB  - The generation of Th1 responses is important for resistance to intracellular
      pathogens, including the parasite, Leishmania major. Although IFN-gammaR/STAT1
      signaling promotes a Th1 response via the up-regulation of T-bet, the requirement
      for STAT1 in Th1 cell differentiation remains controversial. Although in some
      cases Th1 cells develop independently of STAT1, STAT1(-/-) mice fail to develop a
      Th1 response during L. major infection. However, the interpretation of this
      result is complicated by the role STAT1 plays in Ag presentation and, more
      importantly, in elimination of parasites by macrophages, because both defective
      Ag presentation and increased parasite burden can influence Th cell development.
      To resolve this issue, we assessed the ability of STAT1(-/-) T cells to become
      Th1 cells and protect mice against L. major following adoptive transfer into
      STAT1-sufficient mice. We found that whereas T-bet is critical for the
      differentiation of protective Th1 cells during L. major infection, IFN-gammaR and
      STAT1 are dispensable. Given that a STAT1-independent Th1 cell response was
      generated by STAT1-sufficient APCs, but not by STAT1(-/-) cells, we next
      addressed whether dendritic cells (DCs) require STAT1 signaling to effectively
      present Ag. We found that STAT1(-/-) DCs had impaired up-regulation of MHC and
      costimulatory molecules, and, as a consequence, the absence of STAT1 resulted in
      reduced Th1 cell priming. Taken together, these results demonstrate that T cell
      expression of STAT1 is not required for the development of Th1 cells protective
      against L. major and instead stress the importance of STAT1 signaling in DCs for
      the optimal induction of Th1 responses.

PMID- 17513776
TI  - Early virus-associated bystander events affect the fitness of the CD8 T cell
      response to persistent virus infection.
AB  - Chronic Ag exposure during persistent viral infection erodes virus-specific CD8 T
      cell numbers and effector function, with a concomitant loss of pathogen control.
      Less clear are the respective contributions of Ag-specific and Ag-nonspecific
      (bystander) events on the quantity, quality, and maintenance of antiviral CD8 T
      cells responding to persistent virus infection. In this study, we show that low
      dose inoculation with mouse polyomavirus (PyV) elicits a delayed, but numerically
      equivalent, antiviral CD8 T cell response compared with high-dose inoculation.
      Low-dose infection generated virus-specific CD8 T cells endowed with
      multicytokine functionality and a superior per cell capacity to produce IFN
      gamma. PyV-specific CD8 T cells primed by low-dose inoculation also expressed
      higher levels of IL-7Ralpha and bcl-2 and possessed enhanced Ag-independent
      survival. Importantly, the quantity and quality of the antiviral CD8 T cell
      response elicited by dendritic cell-mediated immunization were mitigated by
      infection with a mutant PyV lacking the dominant CD8 T cell viral epitope. These
      findings suggest that the fitness of the CD8 T cell response to persistent virus
      infection is programmed in large part by early virus-associated Ag-nonspecific
      factors, and imply that limiting bystander inflammation at the time of
      inoculation, independent of Ag load, may optimize adaptive immunity to persistent
      viral infection.

PMID- 17513777
TI  - Integrin engagement mediates the human polymorphonuclear leukocyte response to a
      fungal pathogen-associated molecular pattern.
AB  - Extravasation of leukocytes from peripheral blood is required for an effective
      inflammatory response at sites of tissue infection. Integrins help mediate
      extravasation and navigate the leukocyte to the infectious source. A novel role
      for integrins in regulating the effector response to a cell wall component of
      fungal pathogens is the subject of the current study. Although phagocytosis is
      useful for clearance of unicellular fungi, the immune response against large,
      noningestible hyphae is not well-understood. Fungal beta-glucan, a pathogen
      associated molecular pattern, activates production of superoxide anion in
      leukocytes without the need for phagocytosis. To model polymorphonuclear
      leukocyte (PMN) recognition of fungi under conditions in which phagocytosis
      cannot occur, beta-glucan was covalently immobilized onto tissue culture plastic.
      Plasma membrane-associated respiratory burst was measured by reduction of
      ferricytochrome C. Results show that the human PMN oxidative burst response to
      immobilized beta-glucan is suppressed by addition of beta(1) integrin ligands to
      the beta-glucan matrix. Suppression was dose dependent and steric hindrance was
      ruled out. beta(1) integrin ligands did not affect respiratory burst to
      ingestible beta-glucan-containing particles, phorbol esters or live yeast hyphae.
      Furthermore, in the absence of matrix, Ab activation of VLA3 or VLA5, but not
      other beta(1) integrins, also prevented beta-glucan-induced respiratory burst.
      beta(1)-induced suppression was blocked and burst response restored by treating
      neutrophils with either the cell-binding fragment of soluble human Fn, cyclic RGD
      peptide, or Ab specific to VLA3 or VLA5. Together these findings extend the
      functional role of beta(1) integrins to include modulating PMN respiratory burst
      to a pathogen-associated molecular pattern.

PMID- 17513778
TI  - C-reactive protein enhances immunity to Streptococcus pneumoniae by targeting
      uptake to Fc gamma R on dendritic cells.
AB  - C-reactive protein (CRP) is an acute phase reactant with roles in innate host
      defense, clearance of damaged cells, and regulation of the inflammatory response.
      These activities of CRP depend on ligand recognition, complement activation, and
      binding to FcgammaR. CRP binds to phosphocholine in the Streptococcus pneumoniae
      cell wall and provides innate defense against pneumococcal infection. These
      studies examine the effect of this early innate defense molecule on the
      development of Abs and protective immunity to S. pneumoniae. Dendritic cells (DC)
      initiate and direct the adaptive immune response by integrating innate stimuli
      with cytokine synthesis and Ag presentation. We hypothesized that CRP would
      direct uptake of S. pneumoniae to FcgammaR on DC and enhance Ag presentation. CRP
      opsonization of the R36a strain of S. pneumoniae increased the uptake of bacteria
      by DC. DC pulsed with untreated or CRP-opsonized R36a were transferred into
      recipient mice, and Ab responses were measured. In mice challenged with free
      R36a, CRP opsonization resulted in higher secondary and memory IgG responses to
      both phosphocholine and pneumococcal surface protein A. Furthermore, mice
      immunized with DC that had been pulsed with CRP-opsonized R36a showed increased
      resistance to intranasal infection with virulent S. pneumoniae. The effects of
      CRP on Ag uptake, Ab responses, and protection from infection all required FcR
      gamma-chain expression on DC. The results indicate that innate recognition by CRP
      enhances effective uptake and presentation of bacterial Ags through FcgammaR on
      DC and stimulates protective adaptive immunity.

PMID- 17513779
TI  - Dual binding specificity of a Borrelia hermsii-associated complement regulator
      acquiring surface protein for factor H and plasminogen discloses a putative
      virulence factor of relapsing fever spirochetes.
AB  - Tick-borne relapsing fever in North America is primarily caused by the spirochete
      Borrelia hermsii. The pathogen employs multiple strategies, including the
      acquisition of complement regulators and antigenic variation, to escape innate
      and humoral immunity. In this study we identified in B. hermsii a novel member of
      the complement regulator-acquiring surface protein (CRASP) family, designated
      BhCRASP-1, that binds the complement regulators factor H (FH) and FH-related
      protein 1 (FHR-1) but not FH-like protein 1 (FHL-1). BhCRASP-1 specifically
      interacts with the short consensus repeat 20 of FH, thereby maintaining FH
      associated cofactor activity for factor I-mediated C3b inactivation. Furthermore,
      ectopic expression of BhCRASP- 1 converted the serum-sensitive Borrelia
      burgdorferi B313 strain into an intermediate complement-resistant strain.
      Finally, we report for the first time that BhCRASP-1 binds plasminogen/plasmin in
      addition to FH via, however, distinct nonoverlapping domains. The fact that
      surface-bound plasmin retains its proteolytic activity suggest that the dual
      binding specificity of BhCRASP-1 for FH and plasminogen/plasmin contributes to
      both the dissemination/invasion of B. hermsii and its resistance to innate
      immunity.

PMID- 17513780
TI  - A novel RBP-J kappa-dependent switch from C/EBP beta to C/EBP zeta at the C/EBP
      binding site on the C-reactive protein promoter.
AB  - Regulation of basal and cytokine (IL-6 and IL-1beta)-induced expression of C
      reactive protein (CRP) in human hepatoma Hep3B cells occurs during transcription.
      A critical transcriptional regulatory element on the CRP promoter is a C/EBP
      binding site overlapping a NF-kappaB p50 binding site. In response to IL-6,
      C/EBPbeta and p50 occupy the C/EBP-p50 site on the CRP promoter. The aim of this
      study was to identify the transcription factors occupying the C/EBP-p50 site in
      the absence of C/EBPbeta. Accordingly, we treated Hep3B nuclear extract with a
      C/EBP-binding consensus oligonucleotide to generate an extract lacking active
      C/EBPbeta. Such treated nuclei contain only C/EBPzeta (also known as CHOP10 and
      GADD153) because the C/EBP-binding consensus oligonucleotide binds to all C/EBP
      family proteins except C/EBPzeta. EMSA using this extract revealed formation of a
      C/EBPzeta-containing complex at the C/EBP-p50 site on the CRP promoter. This
      complex also contained RBP-Jkappa, a transcription factor known to interact with
      kappaB sites. RBP-Jkappa was required for the formation of C/EBPzeta-containing
      complex. The RBP-Jkappa-dependent C/EBPzeta-containing complexes were formed at
      the C/EBP-p50 site on the CRP promoter in the nuclei of primary human hepatocytes
      also. In luciferase transactivation assays, overexpressed C/EBPzeta abolished
      both C/EBPbeta-induced and (IL-6 + IL-1beta)-induced CRP promoter-driven
      luciferase expression. These results indicate that under basal conditions,
      C/EBPzeta occupies the C/EBP site, an action that requires RBP-Jkappa. Under
      induced conditions, C/EBPzeta is replaced by C/EBPbeta and p50. We conclude that
      the switch between C/EBPbeta and C/EBPzeta participates in regulating CRP
      transcription. This process uses a novel phenomenon, that is, the incorporation
      of RBP-Jkappa into C/EBPzeta complexes solely to support the binding of C/EBPzeta
      to the C/EBP site.

PMID- 17513781
TI  - Inhibition of allergen-induced airway remodeling in Smad 3-deficient mice.
AB  - Intracellular signaling pathways that converge on Smad 3 are used by both TGF
      beta and activin A, key cytokines implicated in the process of fibrogenesis. To
      determine the role of Smad 3 in allergen-induced airway remodeling, Smad 3
      deficient and wild-type (WT) mice were sensitized to OVA and challenged by
      repetitive administration of OVA for 1 mo. Increased levels of activin A and
      increased numbers of peribronchial TGF-beta1(+) cells were detected in WT and
      Smad 3-deficient mice following repetitive OVA challenge. Smad 3-deficient mice
      challenged with OVA had significantly less peribronchial fibrosis (total lung
      collagen content and trichrome staining), reduced thickness of the peribronchial
      smooth muscle layer, and reduced epithelial mucus production compared with WT
      mice. As TGF-beta and Smad 3 signaling are hypothesized to mediate
      differentiation of fibroblasts to myofibroblasts in vivo, we determined the
      number of peribronchial myofibroblasts (Col-1(+) and alpha-smooth muscle
      actin(+)) as assessed by double-label immunofluorescence microscopy. Although the
      number of peribronchial myofibroblasts increased significantly in WT mice
      following OVA challenge, there was a significant reduction in the number of
      peribronchial myofibroblasts in OVA-challenged Smad 3-deficient mice. There was
      no difference in levels of eosinophilic airway inflammation or airway
      responsiveness in Smad 3-deficient compared with WT mice. These results suggest
      that Smad 3 signaling is required for allergen-induced airway remodeling, as well
      as allergen-induced accumulation of myofibroblasts in the airway. However, Smad 3
      signaling does not contribute significantly to airway responsiveness.

PMID- 17513782
TI  - Protection against myocardial ischemia/reperfusion injury in TLR4-deficient mice
      is mediated through a phosphoinositide 3-kinase-dependent mechanism.
AB  - TLRs play a critical role in the induction of innate and adaptive immunity.
      However, TLRs have also been reported to mediate the pathophysiology of organ
      damage following ischemia/reperfusion (I/R) injury. We have reported that TLR4(-/
      ) mice show decreased myocardial injury following I/R; however, the protective
      mechanisms have not been elucidated. We examined the role of the PI3K/Akt
      signaling pathway in TLR4(-/-) cardioprotection following I/R injury. TLR4(-/-)
      and age-matched wild-type (WT) mice were subjected to myocardial ischemia for 45
      min, followed by reperfusion for 4 h. Pharmacologic inhibitors of PI3K
      (wortmannin or LY294002) were administered 1 h before myocardial I/R. Myocardial
      infarct size/area at risk was reduced by 51.2% in TLR4(-/-) vs WT mice. Cardiac
      myocyte apoptosis was also increased in WT vs TLR4(-/-) mice following I/R.
      Pharmacologic blockade of PI3K abrogated myocardial protection in TLR4(-/-) mice
      following I/R. Specifically, heart infarct size/area at risk was increased by 98%
      in wortmannin and 101% in LY294002-treated TLR4(-/-) mice, when compared with
      control TLR4(-/-) mice. These data indicate that protection against myocardial
      I/R injury in TLR4(-/-) mice is mediated through a PI3K/Akt-dependent mechanism.
      The mechanisms by which PI3K/Akt are increased in the TLR4(-/-) myocardium may
      involve increased phosphorylation/inactivation of myocardial phosphatase and
      tensin homolog deleted on chromosome 10 as well as increased
      phosphorylation/inactivation of myocardial glycogen synthase kinase-3beta. These
      data implicate innate immune signaling pathways in the pathology of acute
      myocardial I/R injury. These data also suggest that modulation of TLR4/PI3K/Akt
      dependent signaling pathways may be a viable strategy for reducing myocardial I/R
      injury.

PMID- 17513783
TI  - Soluble TNF-like cytokine (TL1A) production by immune complexes stimulated
      monocytes in rheumatoid arthritis.
AB  - TNF-like cytokine (TL1A) is a newly identified member of the TNF superfamily of
      ligands that is important for T cell costimulation and Th1 polarization. However,
      despite increasing information about its functions, very little is known about
      expression of TL1A in normal or pathological states. In this study, we report
      that mononuclear phagocytes appear to be a major source of TL1A in rheumatoid
      arthritis (RA), as revealed by their strong TL1A expression in either synovial
      fluids or synovial tissue of rheumatoid factor (RF)-seropositive RA patients, but
      not RF-/RA patients. Accordingly, in vitro experiments revealed that human
      monocytes express and release significant amounts of soluble TL1A when stimulated
      with insoluble immune complexes (IC), polyethylene glycol precipitates from the
      serum of RF+/RA patients, or with insoluble ICs purified from RA synovial fluids.
      Monocyte-derived soluble TL1A was biologically active as determined by its
      capacity to induce apoptosis of the human erythroleukemic cell line TF-1, as well
      as to cooperate with IL-12 and IL-18 in inducing the production of IFN-gamma by
      CD4(+) T cells. Because RA is a chronic inflammatory disease with autoimmune
      etiology, in which ICs, autoantibodies (including RF), and various cytokines
      contribute to its pathology, our data suggest that TL1A could be involved in its
      pathogenesis and contribute to the severity of RA disease that is typical of
      RF+/RA patients.

PMID- 17513784
TI  - A peroxynitrite-dependent pathway is responsible for blood-brain barrier
      permeability changes during a central nervous system inflammatory response: TNF
      alpha is neither necessary nor sufficient.
AB  - Elevated blood-brain barrier (BBB) permeability is associated with both the
      protective and pathological invasion of immune and inflammatory cells into CNS
      tissues. Although a variety of processes have been implicated in the changes at
      the BBB that result in the loss of integrity, there has been no consensus as to
      their induction. TNF-alpha has often been proposed to be responsible for
      increased BBB permeability but there is accumulating evidence that peroxynitrite
      (ONOO(-))-dependent radicals may be the direct trigger. We demonstrate here that
      enhanced BBB permeability in mice, whether associated with rabies virus (RV)
      clearance or CNS autoimmunity, is unaltered in the absence of TNF-alpha.
      Moreover, the induction of TNF-alpha expression in CNS tissues by RV infection
      has no impact on BBB integrity in the absence of T cells. CD4 T cells are
      required to enhance BBB permeability in response to the CNS infection whereas CD8
      T cells and B cells are not. Like CNS autoimmunity, elevated BBB permeability in
      response to RV infection is evidently mediated by ONOO(-). However, as opposed to
      the invading cells producing ONOO(-) that have been implicated in the
      pathogenesis of CNS inflammation, during virus clearance ONOO(-) is produced
      without pathological sequelae by IFN-gamma-stimulated neurovascular endothelial
      cells.

PMID- 17513785
TI  - The MyD88-independent pathway is not mobilized in human neutrophils stimulated
      via TLR4.
AB  - LPS activates both MyD88-dependent and -independent signaling via TLR4, but the
      extent to which each cascade is operative in different cell types remains
      unclear. This prompted us to revisit the intriguing issue of CXCL10 production,
      which we previously showed to be inducible in neutrophils stimulated with LPS and
      IFN-gamma but not with either stimulus alone, contrary to other myeloid cells. We
      now report that in neutrophils the MyD88-independent pathway is not activated by
      LPS. Indeed, microarray and real-time PCR experiments showed that neither IFNbeta
      nor IFNbeta-dependent genes (including CXCL10) are inducible in LPS-treated
      neutrophils, in contrast to monocytes. Further investigation into the inability
      of LPS to promote IFNbeta expression in neutrophils revealed that the
      transcription factors regulating the IFNbeta enhanceosome, such as IFN-regulatory
      factor-3 and AP-1, are not activated in LPS-treated neutrophils as revealed by
      lack of dimerization, nuclear translocation, confocal microscopy, and inducible
      binding to DNA. Moreover, we show that the upstream TANK-binding kinase-1 is not
      activated by LPS in neutrophils. A lack of IFNbeta/CXCL10 mRNA expression and IFN
      regulatory factor 3 activation was also observed in myeloid leukemia HL60 cells
      differentiated to granulocytes and then stimulated with LPS, indicating that the
      inability of neutrophils to activate the MyD88-independent pathway represents a
      feature of their terminal maturation. These results identify a disconnected
      activation of the two signaling pathways downstream of TLR4 in key cellular
      components of the inflammatory and immune responses and help us to better
      understand the primordial role of neutrophils in host defense against nonviral
      infections.

PMID- 17513786
TI  - Inactivation of Cdc42 is necessary for depolymerization of phagosomal F-actin and
      subsequent phagosomal maturation.
AB  - Phagocytosis is a complex process involving the activation of various signaling
      pathways, such as the Rho GTPases, and the subsequent reorganization of the actin
      cytoskeleton. In neutrophils, Rac and Cdc42 are activated during phagocytosis but
      less is known about the involvement of these GTPases during the different stages
      of the phagocytic process. The aim of this study was to elucidate the role of
      Cdc42 in phagocytosis and the subsequent phagosomal maturation. Using a TAT-based
      protein transduction technique, we introduced dominant negative and
      constitutively active forms of Cdc42 into neutrophil-like HL60 (human leukemia)
      cells that were allowed to phagocytose IgG-opsonized yeast particles. Staining of
      cellular F-actin in cells transduced with constitutively active Cdc42 revealed
      that the activation of Cdc42 induced sustained accumulation of periphagosomal
      actin. Moreover, the fusion of azurophilic granules with the phagosomal membrane
      was prevented by the accumulated F-actin. In contrast, introducing dominant
      negative Cdc42 impaired the translocation per se of azurophilic granules to the
      periphagosomal area. These results show that efficient phagosomal maturation and
      the subsequent eradication of ingested microbes in human neutrophils is dependent
      on a strictly regulated Cdc42. To induce granule translocation, Cdc42 must be in
      its active state but has to be inactivated to allow depolymerization of the F
      actin cage around the phagosome, a process essential for phagolysosome formation.

PMID- 17513787
TI  - Corticosteroid inhibition of growth-related oncogene protein-alpha via mitogen
      activated kinase phosphatase-1 in airway smooth muscle cells.
AB  - Expression of the inflammatory chemokine, growth-related oncogene protein-alpha
      (GRO-alpha), from airway smooth muscle cells (ASMC) is regulated by pathways
      involving NF-kappaB and MAPK activation. We determined the effects of
      dexamethasone on GRO-alpha induced by IL-1beta or TNF-alpha with respect to the
      role of MAPK pathways and of MAPK phosphatase-1 (MKP-1). Human ASMC were studied
      in primary culture at confluence. Dexamethasone (10(-8)-10(-5) M) partially
      inhibited GRO-alpha expression and release induced by IL-1beta and TNF-alpha;
      this was associated with an inhibition of JNK, but not of p38 or ERK
      phosphorylation. Together with IL-1beta or TNF-alpha, dexamethasone rapidly
      induced mRNA and protein expression of MKP-1, which dephosphorylates MAPKs. Using
      MKP-1 small interfering RNA (siRNA) to block the expression of IL-1beta- and
      dexamethasone-induced MKP-1 by 50%, JNK phosphorylation was doubled. The
      inhibitory effect of dexamethasone on GRO-alpha release was partially reversed in
      ASMC treated with MKP-1 siRNA compared with those treated with scrambled siRNA.
      In contrast, overexpression of MKP-1 led to a reduction in IL-1beta-induced
      release of GRO-alpha, but the inhibitory effects of dexamethasone were preserved.
      Nuclear translocation of the glucocorticoid receptor was increased in ASMC
      exposed to dexamethasone and IL-1beta. Using chromatin immunoprecipitation assay,
      glucocorticoid receptor binding to the MKP-1 promoter was increased by IL-1beta
      and dexamethasone compared with either alone. Glucocorticoids and IL-1beta or TNF
      alpha modulate GRO-alpha release partly through the inhibition of JNK pathway,
      resulting from an up-regulation of MKP-1 expression.

PMID- 17513788
TI  - Nuclear heat shock protein 72 as a negative regulator of oxidative stress
      (hydrogen peroxide)-induced HMGB1 cytoplasmic translocation and release.
AB  - In response to inflammatory stimuli (e.g., endotoxin, proinflammatory cytokines)
      or oxidative stress, macrophages actively release a ubiquitous nuclear protein,
      high-mobility group box 1 (HMGB1), to sustain an inflammatory response to
      infection or injury. In this study, we demonstrated mild heat shock (e.g., 42.5
      degrees C, 1 h), or enhanced expression of heat shock protein (Hsp) 72 (by gene
      transfection) similarly rendered macrophages resistant to oxidative stress
      induced HMGB1 cytoplasmic translocation and release. In response to oxidative
      stress, cytoplasmic Hsp72 translocated to the nucleus, where it interacted with
      nuclear proteins including HMGB1. Genetic deletion of the nuclear localization
      sequence (NLS) or the peptide binding domain (PBD) from Hsp72 abolished oxidative
      stress-induced nuclear translocation of Hsp72-DeltaNLS (but not Hsp72-DeltaPBD),
      and prevented oxidative stress-induced Hsp72-DeltaPBD-HMGB1 interaction in the
      nucleus. Furthermore, impairment of Hsp72-DeltaNLS nuclear translocation, or
      Hsp72-DeltaPBD-HMGB1 interaction in the nucleus, abrogated Hsp72-mediated
      suppression of HMGB1 cytoplasmic translocation and release. Taken together, these
      experimental data support a novel role for nuclear Hsp72 as a negative regulator
      of oxidative stress-induced HMGB1 cytoplasmic translocation and release.

PMID- 17513789
TI  - IFN-gamma protects cerulein-induced acute pancreatitis by repressing NF-kappa B
      activation.
AB  - We explored the pathophysiological roles of IFN-gamma in cerulein-induced acute
      pancreatitis. In wild-type (WT) mice, cerulein injection caused acute
      pancreatitis as evidenced by increased serum amylase levels and pathological
      changes such as interstitial edema, vacuolization, acinar cell necrosis, and
      neutrophil infiltration in pancreas. Concomitantly, cerulein treatment augmented
      intrapancreatic gene expression of TNF-alpha, KC/CXCL1, MIP-2/CXCL2,
      cyclooxygenase-2 (COX-2), and IFN-gamma in WT mice. In situ hybridization
      combined with immunofluorescence analyses demonstrated that infiltrating
      neutrophils expressed IFN-gamma mRNA. Unexpectedly, IFN-gamma(-/-) mice exhibited
      exacerbated cerulein-induced pancreatic injury, with enhanced neutrophil
      recruitment. Moreover, intrapancreatic gene expression of TNF-alpha, KC/CXCL1,
      MIP-2/CXCL2, and COX-2 were significantly exaggerated in IFN-gamma(-/-) mice,
      compared with WT mice. Cerulein activated NF-kappaB, an indispensable
      transcription factor for gene transcription of TNF-alpha, KC/CXCL1, MIP-2/CXCL2,
      and COX-2, in pancreas of cerulein-treated WT mice as evidenced by the increases
      in nuclear amount and DNA-binding activity of NF-kappaB p65. In comparison with
      WT mice, IFN-gamma(-/-) mice exhibited exaggerated and prolonged NF-kappaB
      activation, probably due to reduced acetylation of Stat1, a main signal
      transducer of IFN-gamma, because acetylated Stat1 can inhibit NF-kappaB
      activation. Indeed, IFN-gamma acetylated Stat1 and reciprocally reduced NF-kappaB
      activation and COX-2 expression in neutrophils. Finally, even when administered 4
      h after the first cerulein injection, IFN-gamma remarkably attenuated acute
      pancreatitis in both WT and IFN-gamma(-/-) mice, with reduced NF-kappaB
      activation and COX-2 expression. Thus, IFN-gamma can have anti-inflammatory
      effects on acute pancreatitis by depressing the proinflammatory consequences of
      NF-kappaB activation.

PMID- 17513790
TI  - Proinflammatory proteases liberate a discrete high-affinity functional FPRL1
      (CCR12) ligand from CCL23.
AB  - Most chemokines have been found to bind to and signal through single or highly
      related chemokine receptors. However, a single chemokine protein, a processed
      form of the alternatively spliced CCL23 (CKbeta8/MPIF-1) gene product, potently
      engages both the "classical" chemokine receptor CCR1, as well as FPRL1, a type of
      pattern recognition receptor on innate immune cells. However, the mechanism by
      which the alternative form of CCL23 is processed is unknown. In this study, we
      show that proteases associated with inflammation cleave CCL23 immediately N
      terminal to the 18-residue domain encoded by the alternatively spliced
      nucleotides, resulting in potent CCR1 and FPRL1 activity. The proteases also
      cleave CCL23 immediately C-terminal to the inserted domain, producing a typical
      CC chemokine "body" containing even further-increased CCR1 potency and a released
      approximately 18-aa peptide with full FPRL1 activity but no activity for CCR1.
      This peptide, which we term SHAAGtide, is by itself an attractant of monocytes
      and neutrophils in vitro, recruits leukocytes in vivo, and is 50- to 100-fold
      more potent than all other natural agents posited to act on FPRL1. The appearance
      of SHAAGtide appears to be transient, however, as the proinflammatory proteases
      subsequently cleave within the peptide, abolishing its activity for FPRL1. The
      sequential activation of a transient FPRL1 ligand and a longer-lived CCR1 ligand
      within a single chemokine may have important consequences for the development of
      inflammation or the link between innate and adaptive immunity.

PMID- 17513791
TI  - Expression of Tie-2 by human monocytes and their responses to angiopoietin-2.
AB  - Angiopoietins 1 and 2 bind to Tie-2 expressed on endothelial cells and regulate
      vessel stabilization and angiogenesis. Tie-2(+) monocytes have been shown to be
      recruited to experimental tumors where they promote tumor angiogenesis. In this
      study, we show that 20% of CD14(+) human blood monocytes express Tie-2, and that
      these cells coexpress CD16 (FcgammaRIII) and are predominantly CD34 negative. Ang
      2 is up-regulated by endothelial cells in malignant tumors and inflamed tissues,
      so our finding that Ang-2 is a chemoattractant for human Tie-2(+) monocytes and
      macrophages, suggests that it may help to recruit and regulate their distribution
      in such tissues. Ang-2 was also found to markedly inhibit release of the
      important proinflammatory cytokine, TNF-alpha, by monocytes in vitro. Following
      extravasation of monocytes, and their differentiation into macrophages, many
      accumulate in the hypoxic areas of inflamed and malignant tissues. Ang-2 is known
      to be up-regulated by hypoxia and we show that monocytes and macrophages up
      regulate Tie-2 when exposed to hypoxia. Furthermore, hypoxia augmented the
      inhibitory effect of Ang-2 on the release of the anti-angiogenic cytokine, IL-12
      by monocytes. In sum, our data indicate that Ang-2 may recruit Tie-2(+) monocytes
      to tumors and sites of inflammation, modulate their release of important
      cytokines and stimulate them to express a proangiogenic phenotype.

PMID- 17513792
TI  - Tubulin is a neuronal target of autoantibodies in Sydenham's chorea.
AB  - Sydenham's chorea is a CNS disorder and sequela of group A streptococcal
      infection where deposition of Abs in brain may result in movement and
      neuropsychiatric abnormalities. We studied human mAbs 24.3.1, 31.1.1, and 37.2.1
      derived from chorea and selected for cross-reactivity with group A streptococci
      and brain Ags. Our novel findings reveal that Sydenham's chorea mAbs target a 55
      kDa brain protein with an N-terminal amino acid sequence of MREIVHLQ
      corresponding to beta-tubulin. Chorea mAb specificity for purified brain tubulin
      was confirmed in ELISA and Western immunoblot, and significant levels of anti
      tubulin IgG were found in acute chorea sera and cerebrospinal fluid.
      Lysoganglioside G(M1) inhibited binding of chorea mAbs to tubulin and mAb
      reactivity with human caudate and putamen brain sections was blocked by anti
      tubulin mAb. The chorea mAbs labeled both intra- and extracellular Ags of a
      neuronal cell line providing evidence suggesting mimicry between intracellular
      brain protein tubulin and extracellular lysoganglioside. In addition, chorea mAb
      24.3.1 and acute chorea sera induced calcium/calmodulin-dependent protein kinase
      II activity in human neuronal cells. Nucleotide sequence analysis of the chorea
      mAb V(H) genes revealed that mAb 24.3.1 V(H) gene was encoded by the V(H)1
      germline gene family which encodes other anti-ganglioside V(H) genes associated
      with motor neuropathies. mAb recognition of tubulin and the neuronal cell surface
      with initiation of cell signaling and dopamine release supports an emerging theme
      in autoimmunity whereby cross-reactive or polyreactive autoantibodies against
      intracellular Ags recognize cell surface epitopes potentially leading to disease.

PMID- 17513793
TI  - Abrogation of lupus nephritis in activation-induced deaminase-deficient MRL/lpr
      mice.
AB  - We generated MRL/lpr mice deficient in activation-induced deaminase (AID).
      Because AID is required for Ig hypermutation and class switch recombination,
      these mice lack hypermutated IgG Abs. Unlike their AID wild-type littermates, AID
      deficient MRL/lpr mice not only lacked autoreactive IgG Abs but also experienced
      a dramatic increase in the levels of autoreactive IgM. This phenotype in AID
      deficient mice translated into a significant reduction in glomerulonephritis,
      minimal mononuclear cell infiltration in the kidney, and a dramatic increase in
      survival to levels comparable to those previously reported for MRL/lpr mice
      completely lacking B cells and well below those of mice lacking secreted Abs.
      Therefore, this study wherein littermates with either high levels of autoreactive
      IgM or autoreactive IgG were directly examined proves that autoreactive IgM Abs
      alone are not sufficient to promote kidney disease in MRL/lpr mice. In addition,
      the substantial decrease in mortality combined with a dramatic increase in
      autoreactive IgM Abs in AID-deficient MRL/lpr mice suggest that autoreactive IgM
      Abs might not only fail to promote nephritis but may also provide a protective
      role in MRL/lpr mice. This novel mouse model containing high levels of
      autoreactive, unmutated IgM Abs will help delineate the contribution of
      autoreactive IgM to autoimmunity.

PMID- 17513794
TI  - Soluble Ig-like transcript 3 inhibits tumor allograft rejection in humanized SCID
      mice and T cell responses in cancer patients.
AB  - Attempts to enhance patients' immune responses to malignancies have been largely
      unsuccessful. We now describe an immune-escape mechanism mediated by the
      inhibitory receptor Ig-like transcript 3 (ILT3) that may be responsible for such
      failures. Using a humanized SCID mouse model, we demonstrate that soluble and
      membrane ILT3 induce CD8(+) T suppressor cells and prevent rejection of
      allogeneic tumor transplants. Furthermore, we found that patients with melanoma,
      and carcinomas of the colon, rectum, and pancreas produce the soluble ILT3
      protein, which induces the differentiation of CD8(+) T suppressor cells and
      impairs T cell responses in MLC. These responses are restored by anti-ILT3 mAb or
      by depletion of soluble ILT3 from the serum. Immunohistochemical staining of
      biopsies from the tumors and metastatic lymph nodes suggests that CD68(+) tumor
      associated macrophages represent the major source of soluble ILT3. Alternative
      splicing, resulting in the loss of the ILT3 transmembrane domain, may contribute
      to the release of ILT3 in the circulation. These data suggest that ILT3 depletion
      or blockade is crucial to the success of immunotherapy in cancer. In contrast,
      the inhibitory activity of soluble ILT3 on T cell alloreactivity in vitro and in
      vivo suggests the potential usefulness of rILT3 for immunosuppressive treatment
      of allograft recipients or patients with autoimmune diseases.

PMID- 17513795
TI  - Novel insight into the agonistic mechanism of alefacept in vivo: differentially
      expressed genes may serve as biomarkers of response in psoriasis patients.
AB  - Alefacept is an LFA3-Ig fusion protein that binds to CD2 and is thought to
      inhibit T cell activation by antagonism of CD2 signaling or by lysis of CD2(+)
      cells. Alefacept is potential future therapeutic for organ transplant recipients
      or graft-vs-host disease and is an approved therapeutic for psoriasis vulgaris,
      which is a T cell-mediated inflammatory disease. However, alefacept improves
      psoriasis in only approximately 50% of patients treated for 12 wk. We studied the
      immunologic effects of alefacept in a group of psoriasis patients during
      treatment. We found that T cells, especially CD8(+) T cells, were rapidly
      decreased in the peripheral circulation. Decreases in circulating T cells were
      not associated with induced apoptosis. Unexpectedly, in addition to suppression
      of inflammatory genes, we found a marked induction of mRNAs for STAT1, IL-8, and
      monokine induced by IFN-gamma during the first day of treatment in PBMC. We
      confirmed the agonistic effects of alefacept in PBMC in vitro, which were similar
      to CD3/CD28 ligation on T cells. These data establish that alefacept activates
      gene expression programs in leukocytes and suggest that its therapeutic action
      may be as a mixed agonist/antagonist. Furthermore, responding patients to
      alefacept treatment show unique patterns of gene modulation. Whereas alefacept
      down-regulated TCRs CD3D and CD2 in responders, nonresponders reveal a higher
      expression of T cell activation genes such as CD69 in pretreatment PBMC. These
      finding suggest a potential basis for categorizing responders vs nonresponders at
      an early time point in treatment or before treatment of a broad range of
      proinflammatory diseases. This study 1) establishes alefacept as a novel CD2
      agonist molecule for induction of leukocyte activation genes (prior work proposed
      its mechanism as a CD2 antagonist) and 2) that differential activation of genes
      may categorize clinical responders to this agent, critical for cost-effective use
      of this drug.

PMID- 17513796
TI  - A virus-like particle-based vaccine selectively targeting soluble TNF-alpha
      protects from arthritis without inducing reactivation of latent tuberculosis.
AB  - Neutralization of the proinflammatory cytokine TNF-alpha by mAbs or soluble
      receptors represents an effective treatment for chronic inflammatory disorders
      such as rheumatoid arthritis, psoriasis, or Crohn's disease. In this study, we
      describe a novel active immunization approach against TNF-alpha, which results in
      the induction of high titers of therapeutically active autoantibodies.
      Immunization of mice with virus-like particles of the bacteriophage Qbeta
      covalently linked to either the entire soluble TNF-alpha protein (Qbeta-C-TNF(1
      156)) or a 20-aa peptide derived from its N terminus (Qbeta-C-TNF(4-23)) yielded
      specific Abs, which protected from clinical signs of inflammation in a murine
      model of rheumatoid arthritis. Whereas mice immunized with Qbeta-C-TNF(1-156)
      showed increased susceptibility to Listeria monocytogenes infection and enhanced
      reactivation of latent Mycobacterium tuberculosis, mice immunized with Qbeta-C
      TNF(4-23) were not immunocompromised with respect to infection with these
      pathogens. This difference was attributed to recognition of both transmembrane
      and soluble TNF-alpha by Abs elicited by Qbeta-C-TNF(1-156), and a selective
      recognition of only soluble TNF-alpha by Abs raised by Qbeta-C-TNF(4-23). Thus,
      by specifically targeting soluble TNF-alpha, Qbeta-C-TNF(4-23) immunization has
      the potential to become an effective and safe therapy against inflammatory
      disorders, which might overcome the risk of opportunistic infections associated
      with the currently available TNF-alpha antagonists.

PMID- 17513797
TI  - Immunization of HLA class I transgenic mice identifies autoantigenic epitopes
      eliciting dominant responses in type 1 diabetes patients.
AB  - Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic beta
      cells. CD8(+) T cells have recently been assigned a major role in beta cell
      injury. Consequently, the identification of autoreactive CD8(+) T cells in humans
      remains essential for development of therapeutic strategies and of assays to
      identify aggressive cells. However, this identification is laborious and limited
      by quantities of human blood samples available. We propose a rapid and reliable
      method to identify autoantigen-derived epitopes recognized by human CD8(+) T
      lymphocytes in T1D patients. Human histocompatibility leukocyte Ags-A*0201 (HLA
      A*0201) transgenic mice were immunized with plasmids encoding the T1D-associated
      autoantigens: 65 kDa glutamic acid decarboxylase (GAD) or insulinoma-associated
      protein 2 (IA-2). Candidate epitopes for T1D were selected from peptide libraries
      by testing the CD8(+) reactivity of vaccinated mice. All of the nine-candidate
      epitopes (five for GAD and four for IA-2) identified by our experimental approach
      were specifically recognized by CD8(+) T cells from newly diagnosed T1D patients
      (n = 19) but not from CD8(+) T cells of healthy controls (n = 20). Among these,
      GAD(114-123), GAD(536-545) and IA-2(805-813) were recognized by 53%, 25%, and 42%
      of T1D patients, respectively.

PMID- 17513798
TI  - Comparing ELISA and surface plasmon resonance for assessing clinical
      immunogenicity of panitumumab.
AB  - Evaluation of the immunogenicity of panitumumab, a fully human anti-epidermal
      growth factor receptor mAb approved for use in colorectal cancer patients, led to
      the development of two separate immunoassays for the detection of anti
      panitumumab Abs. The first immunoassay used a bridging ELISA capable of detecting
      10 ng/ml positive control anti-panitumumab Ab. The ELISA incorporated an acid
      dissociation step to reduce drug interference and tolerated the presence of
      approximately 100-fold molar excess of drug. During eight clinical trials, the
      ELISA detected developing Ab responses in 2 of 612 (0.3%) subjects. In one of the
      ELISA positive subjects, neutralizing Abs were detected using an epidermal growth
      factor receptor phosphorylation bioassay. The second immunoassay used a Biacore
      biosensor immunoassay format capable of detecting 1 mug/ml positive control Ab
      while tolerating the presence of equal molar amounts of drug. Although less
      sensitive and less tolerant to competing drug in the assay, the Biacore assay
      detected developing Ab responses in 25 of the 604 (4.1%) subjects. Additionally,
      the Biacore assay identified eight subjects who developed neutralizing Abs. Mouse
      mAbs with affinities ranging from 1.1 x 10(-6) to 8.4 x 10(-10) M were used to
      characterize both assay types. The ELISA was more sensitive for the detection of
      higher affinity mAbs and detected high-affinity mAbs in the presence of higher
      molar ratio of drug to mAb. The Biacore assay was more sensitive for detection of
      lower affinity mAbs and detected low affinity Abs in the presence of higher molar
      ratios of drug to mAb.

PMID- 17513799
TI  - Enhanced immune reconstitution by sex steroid ablation following allogeneic
      hemopoietic stem cell transplantation.
AB  - Delayed immune reconstitution in adult recipients of allogeneic hemopoietic stem
      cell transplantations (HSCT) is related to age-induced thymic atrophy. Overcoming
      this paucity of T cell function is a major goal of clinical research but in the
      context of allogeneic transplants, any strategy must not exacerbate graft-vs-host
      disease (GVHD) yet ideally retain graft-vs-tumor (GVT) effects. We have shown sex
      steroid ablation reverses thymic atrophy and enhances T cell recovery in aged
      animals and in congenic bone marrow (BM) transplant but the latter does not have
      the complications of allogeneic T cell reactivity. We have examined whether sex
      steroid ablation promoted hemopoietic and T cell recovery following allogeneic
      HSCT and whether this benefit was negated by enhanced GVHD. BM and thymic cell
      numbers were significantly increased at 14 and 28 days after HSCT in castrated
      mice compared with sham-castrated controls. In the thymus, the numbers of donor
      derived thymocytes and dendritic cells were significantly increased after HSCT
      and castration; donor-derived BM precursors and developing B cells were also
      significantly increased. Importantly, despite restoring T cell function, sex
      steroid inhibition did not exacerbate the development of GVHD or ameliorate GVT
      activity. Finally, IL-7 treatment in combination with castration had an additive
      effect on thymic cellularity following HSCT. These results indicate that sex
      steroid ablation can profoundly enhance thymic and hemopoietic recovery following
      allogeneic HSCT without increasing GVHD and maintaining GVT.

PMID- 17513800
TI  - Skin squamous cell cancer: the time is right for greater involvement of the
      medical oncologist.

PMID- 17513801
TI  - Addition of histone deacetylase inhibitors in combination therapy.

PMID- 17513802
TI  - Chromogranin A: is it a useful marker of neuroendocrine tumors?
AB  - PURPOSE: We evaluated the pattern of chromogranin A (CgA) plasma levels in a
      large number of patients with neuroendocrine tumors (NETs), in a series of
      patients with chronic atrophic gastritis (CAG) with and without enterochromaffin
      like (ECL) cell hyperplasia, and in healthy participants (HPs). PATIENTS AND
      METHODS: Two hundred thirty-eight patients with NETs, 42 patients with CAG with
      or without ECL cell hyperplasia, and 48 HPs were studied. All patients underwent
      a baseline visit, biochemical routine check-up, imaging techniques, endoscopy,
      and histologic determination. RESULTS: CgA plasma levels were higher in patients
      with NETs compared with CAG patients or HPs (P < .001). In the NET group, we
      observed higher CgA levels in patients with diffuse disease compared with
      patients with local or hepatic disease (P < .001). CgA plasma levels were
      significantly higher in patients with Zollinger-Ellison syndrome compared with
      other types of endocrine tumors (P < .001). We found the best cutoff range
      between HPs and NET patients to be 18 to 19 U/L (sensitivity, 85.3%; specificity,
      95.8%). Comparing all participants without neoplasia (HPs, CAG patients, and
      disease-free patients) and patients with endocrine tumors, the best cutoff range
      was 31 to 32 U/L (sensitivity, 75.3%; specificity, 84.2%). Setting the
      specificity at 95%, the cutoff range was 84 to 87 U/L (sensitivity, 55%).
      CONCLUSION: Our study confirms the high specificity and sensitivity of CgA in
      diagnosing an endocrine tumor. It is necessary to use a cutoff range of 84 to 87
      U/L to obtain a high specificity in diagnosing NETs, with the aim of excluding
      patients in whom the CgA was elevated as a result of other non-neoplastic
      diseases.

PMID- 17513803
TI  - Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for
      patients with aggressive skin squamous cell carcinoma.
AB  - PURPOSE: To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA)
      plus interferon alfa (IFN-alpha) for preventing tumor recurrence and second
      primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with
      aggressive skin SCC. PATIENTS AND METHODS: Sixty-six patients with aggressive
      skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1
      mg/kg/d orally) and IFN-alpha (3 x 10(6) U subcutaneously three times per week)
      or no adjuvant therapy (control group) after SCC surgery and/or radiation.
      RESULTS: At 21.5 months median follow-up, treatment did not improve the time to
      tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to
      2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT
      (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN-alpha was moderately
      tolerable; 29% of patients in the treatment arm required dose reductions for
      grade 3 or 4 toxicities. CONCLUSION: Results of this phase III trial do not
      support 13cRA plus IFN-alpha for adjuvant therapy of aggressive skin SCC. With
      high rates of tumor recurrence and SPTs, patients with aggressive skin SCC
      continue to have an unmet medical need, with devastating mortality, morbidity,
      and financial consequences. Promising agents with preclinical and early clinical
      results relevant to aggressive skin SCC deserve a high priority for future
      clinical drug development.

PMID- 17513804
TI  - Phase I trial of histone deacetylase inhibition by valproic acid followed by the
      topoisomerase II inhibitor epirubicin in advanced solid tumors: a clinical and
      translational study.
AB  - PURPOSE: To determine the safety, toxicity, and maximum-tolerated dose of a
      sequence-specific combination of the histone deacetylase inhibitor (HDACi),
      valproic acid (VPA), and epirubicin in solid tumor malignancies and to define the
      clinical feasibility of VPA as an HDACi. PATIENTS AND METHODS: Patients were
      treated with increasing doses of VPA (days 1 through 3) followed by epirubicin
      (day 3) in 3-week cycles. The study evaluated pharmacokinetic and pharmacodynamic
      end points, toxicities, and tumor response. RESULTS: Forty-eight patients were
      enrolled, and 44 received at least one cycle of therapy. Patients (median age, 54
      years; range, 39 to 78 years) received the following doses of VPA: 15, 30, 45,
      60, 75, 90, 100, 120, 140, and 160 mg/kg/d. Dose-limiting toxicities were
      somnolence (n = 1), confusion (n = 3), and febrile neutropenia (n = 1). No
      exacerbation of epirubicin-related toxicities was observed. Partial responses
      were seen across different tumor types in nine patients (22%), and stable
      disease/minor responses were seen in 16 patients (39%), despite a median number
      of three prior regimens (range, zero to 10 prior regimens). Patients received a
      median number of four treatment cycles (range, one to 10 cycles), and treatment
      was stopped after reaching maximal epirubicin doses rather than progression in 13
      (32%) of 41 patients patients. Total and free VPA plasma concentrations increased
      linearly with dose and correlated with histone acetylation in peripheral-blood
      mononuclear cells. CONCLUSION: The maximum-tolerated dose and recommended phase
      II dose was VPA 140 mg/kg/d for 48 hours followed by epirubicin 100 mg/m2.
      Sustained plasma concentrations of VPA exceeding those required for in vitro
      synergy were achieved with acceptable toxicity. Noteworthy antitumor activity was
      observed in heavily pretreated patients and historically anthracycline-resistant
      tumors.

PMID- 17513805
TI  - Pathologic complete response with six compared with three cycles of neoadjuvant
      epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable
      breast cancer: results of ABCSG-14.
AB  - PURPOSE: Preoperative (neoadjuvant) chemotherapy for operable breast cancer
      downstages tumors initially not suitable for breast-conserving surgery. A
      pathologic complete response (pCR) to neoadjuvant chemotherapy may be a surrogate
      for longer overall survival, but this beneficial effect remains to be
      established. This phase III trial evaluated whether doubling the number of cycles
      of neoadjuvant treatment increased the pCR rate. PATIENTS AND METHODS: Patients
      with biopsy-proven breast cancer (T1-4a-c, N+/-, M0; stage I to III) were
      eligible and randomly assigned to either three or six cycles of epirubicin 75
      mg/m2 and docetaxel 75 mg/m2 on day 1 and granulocyte colony-stimulating factor
      on days 3 through 10 (ED+G), every 21 days. The primary end point was the pCR
      rate of the breast tumor. Secondary end points were pathologic nodal status after
      surgery and the rate of breast-conserving surgery. RESULTS: A total of 292
      patients were accrued, and 288 patients were assessable for efficacy and safety.
      Groups were well balanced for known prognostic factors. Six cycles of ED+G,
      compared with three cycles, resulted in a significantly higher pCR rate (18.6% v
      7.7%, respectively; P = .0045), a higher percentage of patients with negative
      axillary status (56.6% v 42.8%, respectively; P = .02), and a trend towards more
      breast-conserving surgery (75.9% v 66.9%, respectively; P = .10). Rates of
      adverse events were similar, and no patients died on treatment. CONCLUSION:
      Doubling the number of neoadjuvant ED+G cycles from three to six results in
      higher rates of pCR and negative axillary nodal status with no excess of adverse
      effects. Thus, six cycles of ED+G should be the standard neoadjuvant treatment
      for operable breast cancer if this combination is chosen.

PMID- 17513806
TI  - Screening for a BRCA2 rearrangement in high-risk breast/ovarian cancer families:
      evidence for a founder effect and analysis of the associated phenotypes.
AB  - PURPOSE: BRCA2 rearrangements are rare genetic events. A large BRCA2 genomic
      insertion was recurrently observed in our participants, and we sought to
      characterize it at the molecular and phenotypic level. PATIENTS AND METHODS: We
      studied 210 high-risk breast/ovarian cancer families. Fifty-three probands were
      fully screened for BRCA1/2 mutations, and three of 53 had a large insertion in
      exon 3 of BRCA2. This finding was analyzed by polymerase chain reaction (PCR),
      reverse transcriptase PCR (RT-PCR), and sequencing. An additional 157 consecutive
      families were screened for this mutation by a three-step PCR method. Phenotype
      and haplotype analysis was also performed. RESULTS: Sixteen BRCA mutations were
      observed in 19 of 53 patients (36% detection rate). A recurrent Alu motif
      insertion in position c.156_157 was observed after sequencing of an abnormal
      fragment obtained after the amplification of BRCA2 exon 3. RT-PCR revealed exon 3
      skipping. Screening of this rearrangement identified 14 additional families (out
      of 157). In total, 17 (8%) of 210 high-risk families ascertained in our clinic
      were positive for this mutation. Segregation of a common haplotype (from D13S260
      to D13S1695) confirmed a common origin, estimated to have occurred 2,400 to 2,600
      years ago. The following four cancer phenotypes were observed in the 17 positive
      families: female breast (n = 9), male breast (n = 4), breast/ovarian (n = 2), and
      heterogeneous (n = 2). Male breast cancer was more frequently observed in
      c.156_157insAlu-positive families compared with negative families (23% v 12%,
      respectively), and 33% of all male breast cancer families with an identified BRCA
      mutation were c.156_157insAlu positive. CONCLUSION: c.156_157insAlu is a founder
      mutation of Portuguese origin and is the most frequent BRCA2 rearrangement
      described to date.

PMID- 17513807
TI  - Predicting the outcome of salvage radiation therapy for recurrent prostate cancer
      after radical prostatectomy.
AB  - PURPOSE: An increasing serum prostate-specific antigen (PSA) level is the initial
      sign of recurrent prostate cancer among patients treated with radical
      prostatectomy. Salvage radiation therapy (SRT) may eradicate locally recurrent
      cancer, but studies to distinguish local from systemic recurrence lack adequate
      sensitivity and specificity. We developed a nomogram to predict the probability
      of cancer control at 6 years after SRT for PSA-defined recurrence. PATIENTS AND
      METHODS: Using multivariable Cox regression analysis, we constructed a model to
      predict the probability of disease progression after SRT in a multi-institutional
      cohort of 1,540 patients. RESULTS: The 6-year progression-free probability was
      32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of
      patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease
      free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling
      time of 10 months or less or poorly differentiated (Gleason grade 8 to 10)
      cancer. Significant variables in the model were PSA level before SRT (P < .001),
      prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical
      margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001),
      and lymph node metastasis (P = .019). The resultant nomogram was internally
      validated and had a concordance index of 0.69. CONCLUSION: Nearly half of
      patients with recurrent prostate cancer after radical prostatectomy have a long
      term PSA response to SRT when treatment is administered at the earliest sign of
      recurrence. The nomogram we developed predicts the outcome of SRT and should
      prove valuable for medical decision making for patients with a rising PSA level.

PMID- 17513808
TI  - Microsatellite instability and epigenetic inactivation of MLH1 and outcome of
      patients with endometrial carcinomas of the endometrioid type.
AB  - PURPOSE: Most studies of microsatellite instability (MSI) and outcomes in
      endometrial cancer patients have included varied histologic subtypes.
      Nonetheless, MSI occurs almost exclusively in endometrioid tumors. The impact of
      MSI on outcomes in patients with endometrial cancer is controversial. We sought
      to determine whether MSI and MLH1 methylation are associated with
      clinicopathologic variables and survival outcomes in a large series of patients
      with endometrial carcinomas of the endometrioid type. PATIENTS AND METHODS: Tumor
      samples, blood, and clinicopathologic data were prospectively collected and
      analyzed for 446 patients with endometrioid carcinomas. MSI was determined using
      five National Cancer Institute (NCI) consensus panel markers, and the methylation
      status of the MLH1 promoter was determined by combined bisulfite restriction
      analysis (COBRA). Associations with clinicopathologic variables and survival
      outcomes were evaluated. RESULTS: MSI was identified in 147 cases (33%). MSI was
      associated with higher International Federation of Gynecology and Obstetrics
      (FIGO) grade (P < .0001). MSI+ tumors without MLH1 methylation were associated
      with younger age (P < .001). MSI was not associated with overall survival (OS;
      hazard ratio [HR], 1.011; 95% CI, 0.688 to 1.484; P = .96) or disease-free
      survival (DFS; HR 0.951; 95% CI, 0.554 to 1.635; P = .86). The combined MSI/MLH1
      methylation status (treating MSI- as the reference) did not predict OS (MSI+/MLH1
      U: HR, 0.62; 95% CI, 0.27 to 1.44; P = .26; MSI+/MLH1-M: HR, 0.95; 95% CI, 0.62
      to 1.46; P = .82) or DFS (MSI+/MLH1-U: HR, 0.51; 95% CI, 0.22 to 1.19; P = .12;
      MSI+/MLH1-M: HR, 0.93; 95% CI, 0.62 to 1.40; P = .72). CONCLUSION: MSI is not
      associated with survival in patients with endometrioid endometrial cancer.

PMID- 17513809
TI  - Controlled study of fatigue, quality of life, and somatic and mental morbidity in
      epithelial ovarian cancer survivors: how lucky are the lucky ones?
AB  - PURPOSE: There are few studies of somatic and mental morbidity in epithelial
      ovarian cancer survivors (EOCSs). The aim of this controlled, cross-sectional
      study was to explore fatigue, quality of life (QOL), and somatic and mental
      morbidity in EOCSs. PATIENTS AND METHODS: Among 287 EOCSs treated according to
      protocols at The Norwegian Radium Hospital between 1977 and 2003, 189 patients
      (66%) participated. Information was collected by a questionnaire containing
      demographic and morbidity items and self-rating scales. Internal comparisons of
      various subgroups of EOCSs were performed, and EOCSs were compared with age
      adjusted controls from the general population. RESULTS: Minimal differences were
      observed relating to somatic and mental morbidity, fatigue, and QOL between EOCSs
      with and without relapse, long or short follow-up time, and prognostic index
      status. Chronic fatigue was found in 22% (95% CI, 16% to 28%), and only body
      image was significantly associated with chronic fatigue in multivariable
      analyses. EOCSs showed significantly more somatic and mental morbidity, somatic
      complaints, use of medications, and use of health care services than controls.
      The levels of anxiety and fatigue were also significantly higher in EOCSs than in
      controls, whereas the levels of depression and of several QOL dimensions were
      lower. The prevalence of chronic fatigue was 12% among controls. CONCLUSION:
      EOCSs had more somatic and mental morbidity, more fatigue, poorer QOL, and used
      more medication and health services than controls. Minimal differences were
      observed between various EOCS subgroups. Health care professionals should try to
      improve and be attentive to the health of EOCSs.

PMID- 17513810
TI  - Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children's
      Oncology Group.
AB  - PURPOSE: Multiple drug resistance due to P-glycoprotein (P-gp) expression has
      been reported to be a cause of disease recurrence in osteosarcoma. Tumor
      specimens derived from children and young adults with osteosarcoma enrolled onto
      a national Intergroup trial (INT0133) were analyzed prospectively to determine
      the role of multiple drug resistance in osteosarcoma. PATIENTS AND METHODS: From
      October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade
      osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor
      specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients)
      and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery
      (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as
      outcome measures for patients with P-gp-positive disease and were compared with
      patients with P-gp-negative disease. RESULTS: P-gp expression in the biopsy
      specimen did not significantly increase the risk for adverse outcomes as measured
      by EFS, OS, or NEC. EFS for those patients with C-494-positive tumors was 59% at
      4 years versus 61% at 4 years for patients with C-494-negative tumors (P = .79),
      or 58% at 4 years versus 61% at 4 years for patients with JSB-1-positive versus
      JSB-1-negative tumors (P = .65). OS for patients with C-494-positive tumors was
      82% at 4 years versus 82% at 4 years for patients with C-494-negative tumors (P =
      .61). CONCLUSION: Prospective analysis of the role of multiple drug resistance in
      localized osteosarcoma did not find that immunohistochemical analysis of P-gp
      expression predicted outcome for patients treated on INT0133.

PMID- 17513811
TI  - Obesity and outcome in pediatric acute lymphoblastic leukemia.
AB  - PURPOSE: To evaluate the effect of obesity (defined as a body mass index > 95th
      percentile for age and sex at diagnosis) on outcome of pediatric acute
      lymphoblastic leukemia (ALL). PATIENTS AND METHODS: We retrospectively analyzed
      data from 4,260 patients with newly diagnosed ALL enrolled from 1988 to 1995 onto
      five concurrent Children's Cancer Group studies. Results were verified in a
      second cohort of 1,733 patients enrolled onto a sixth study from 1996 to 2002.
      RESULTS: The 1988 to 1995 cohort included 343 obese and 3,971 nonobese patients.
      The 5-year event-free survival rate and risk of relapse in obese versus nonobese
      patients were 72% +/- 2.4% v 77% +/- 0.6% (P = .02) and 26 +/- 2.4 v 20 +/- 0.6
      (P = .02), respectively. After adjusting for other prognostic variables,
      obesity's hazard ratios (HRs) of events and relapses were 1.36 (95% CI, 1.04 to
      1.77; P = .021) and 1.29 (95% CI, 1.02 to 1.56; P = .04), respectively. The
      effect of obesity was prominent in the 1,003 patients > or = 10 years old at
      diagnosis; in this subset, obesity's adjusted HRs of events and relapses were 1.5
      (95% CI, 1.1 to 2.1; P = .009) and 1.5 (95% CI, 1.2 to 2.1; P = .013),
      respectively. In a second cohort of 1,160 patients 10 years old, obesity's
      adjusted HRs of events and relapses were 1.42 (95% CI, 1.03 to 1.96; P = .032)
      and 1.65 (95% CI, 1.13 to 2.41; P = .009), respectively. The effect of obesity on
      outcome was unrelated to changes in chemotherapy doses, length of intervals
      between chemotherapy cycles, or incidence and severity of therapy-related
      toxicity. CONCLUSION: Obesity at diagnosis independently predicts likelihood of
      relapse and cure in preteenagers and adolescents with ALL.

PMID- 17513812
TI  - Criteria for optimizing prognostic risk groups in pediatric cancer: analysis of
      data from the Children's Oncology Group.
AB  - PURPOSE: Physicians who treat cancer often attempt to identify patient subgroups
      that are homogeneous in their chance of recurrence or death as a way to target
      the more toxic and presumably more effective treatments to patients with the
      worst prognosis. However, to date, prognosis-based treatment assignment in
      pediatric cancer has not been based on a quantitative assessment of the risks and
      benefits of different treatment strategies or on morbidity and efficacy outcome
      measures that are relevant to children. METHODS: We performed a quantitative
      analysis of the risks and benefits of prognosis-based treatment assignment in two
      examples from the Children's Oncology Group using a mathematical model of cancer
      cure and permanent treatment morbidity and defined an optimality criterion for
      assigning treatments to specific risk groups. RESULTS: In stage 4 MYCN
      unamplified neuroblastoma, age-based risk grouping distinguishes clearly between
      patients with high and low risk of recurrence. However, our analysis suggests
      that the optimal age cut point depends profoundly on the morbidity of the
      treatments being considered and agrees with current published recommendations
      only for treatments that add significant morbidity. In Hodgkin's lymphoma, under
      our model, no clearly optimal risk groupings exist, and a compelling quantitative
      rationale for defining risks group at all may not exist. CONCLUSION: Our analysis
      illustrates the inadequacy of naive application of statistical criteria for
      defining prognostic risk groups in pediatric cancer and highlights the importance
      of quantifying treatment morbidity when defining risk groups or when deciding
      whether risk grouping is warranted.

PMID- 17513813
TI  - Randomized trial of an allogeneic melanoma lysate vaccine with low-dose
      interferon Alfa-2b compared with high-dose interferon Alfa-2b for Resected stage
      III cutaneous melanoma.
AB  - PURPOSE: To compare the overall survival (OS) of patients with resected stage III
      melanoma administered active specific immunotherapy and low-dose interferon alfa
      2b (IFN-alpha-2b) with the OS achieved using high-dose IFN-alpha-2b. PATIENTS AND
      METHODS: An Ad Hoc Melanoma Working Group of 25 investigators treated 604
      patients from April 1997 to January 2003. Patients were stratified by sex and
      number of nodes and were randomly assigned to receive either 2 years of treatment
      with active specific immunotherapy with allogeneic melanoma lysates and low-dose
      IFN-alpha-2b (arm 1) or high-dose IFN-alpha-2b alone for 1 year (arm 2). Active
      specific immunotherapy was injected subcutaneously (SC) weekly for 4 weeks, at
      week 8, and bimonthly thereafter. IFN-alpha-2b SC was begun on week 4 and
      continued thrice weekly at 5 MU/m2 for 2 years. IFN-alpha-2b in arm 2 was
      administered according to the Eastern Cooperative Oncology Group 1684 study
      regimen. RESULTS: Median follow-up time was 32 months for all patients and 42
      months for surviving patients. Median OS time exceeds 84 months in arm 1 and is
      83 months in arm 2 (P = .56). Five-year OS rate is 61% in arm 1 and 57% in arm 2.
      Estimated 5-year relapse-free survival (RFS) rate is 50% in arm 1 and 48% in arm
      2, with median RFS times of 58 and 50 months, respectively. The incidence of
      serious adverse events as a result of treatment was the same in both arms, but
      more severe neuropsychiatric toxicity was seen in arm 2. CONCLUSION: OS and RFS
      achieved by active specific immunotherapy and low-dose IFN-alpha-2b were
      indistinguishable from those achieved by high-dose IFN-alpha-2b. Long RFS and OS
      times were observed in both treatment arms.

PMID- 17513814
TI  - Phase III study of oral compared with intravenous topotecan as second-line
      therapy in small-cell lung cancer.
AB  - PURPOSE: Single-agent intravenous (IV) topotecan is an effective treatment for
      small-cell lung cancer (SCLC) after failure of first-line chemotherapy. This open
      label, randomized, phase III study compared oral and IV topotecan in patients
      with SCLC sensitive to initial chemotherapy. PATIENTS AND METHODS: Patients with
      limited- or extensive-disease SCLC, documented complete or partial response to
      first-line therapy, Eastern Cooperative Oncology Group performance status < or =
      2, and measurable recurrent disease (WHO criteria) with a treatment-free interval
      of > or = 90 days were assigned to treatment with either oral topotecan 2.3
      mg/m2/d on days 1 through 5 or IV topotecan 1.5 mg/m2/d on days 1 through 5 every
      21 days. Primary end point was response rate as confirmed by an external reviewer
      blinded to treatment. RESULTS: A total of 309 patients were randomly assigned. In
      intent-to-treat analysis, response rates were 18.3% with oral topotecan (n = 153)
      and 21.9% with IV topotecan (n = 151), with a difference (oral -IV) of -3.6% (95%
      CI, -12.6% to 5.5%). Median survival time was 33.0 weeks for oral and 35.0 weeks
      for IV topotecan; 1- and 2-year survival rates were 32.6% and 12.4% for oral
      topotecan, respectively, and 29.2% and 7.1% for IV topotecan, respectively. Third
      line chemotherapy was similar for both groups (33% for oral; 35% for IV).
      Incidence of grade 4 toxicity in patients who received oral and IV topotecan was
      as follows: neutropenia in 47% and 64%, thrombocytopenia in 29% and 18%, grade 3
      or 4 anemia in 23% and 31%, and sepsis in 3% and 3%, respectively. The most
      frequent nonhematologic adverse events (all grades) included nausea (43% oral;
      42% IV), alopecia (26% oral; 30% IV), fatigue (31% oral; 36% IV), and diarrhea
      (36% oral; 20% IV). CONCLUSION: Oral topotecan demonstrates activity and
      tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and
      offers patients a convenient alternative to IV therapy.

PMID- 17513816
TI  - Provider counseling about health behaviors among cancer survivors in the United
      States.
AB  - PURPOSE: To examine provider discussion or counseling of US cancer survivors
      about diet, exercise, and tobacco use. METHODS: We used 2000 National Health
      Interview Survey data to examine whether US cancer survivors reported that,
      within 1 year, a provider (1) discussed diet, (2) recommended they begin or
      continue exercise, or (3) asked about smoking. We included survivors more than 1
      year beyond diagnosis (n = 1,600) and adults without cancer (AWCs; n = 24,636)
      who saw/talked to a provider within 1 year. We used generalized linear contrasts
      in bivariable analyses and logistic regression to calculate predicted marginals
      adjusted for age, sex, comorbidity, usual source of care, and number of provider
      visits in the prior year. RESULTS: Few survivors reported discussions or
      recommendations for all three health behaviors (10% of survivors v 9% of AWCs; P
      = .57). Although report was more likely than among AWCs, few survivors reported
      diet discussions (30% of survivors v 23% of AWCs; P < .0001) or exercise
      recommendations (26% of survivors v 23% of AWCs; P < .005), and a minority were
      asked about smoking (42% of survivors v 41% of AWCs; P = .41). After adjustment,
      survivors were less likely to report exercise recommendations than were AWCs (22%
      v 24%, respectively; P = .02). Colorectal cancer survivors were less likely than
      were AWCs of similar age range to report exercise recommendations (16% v 27%,
      respectively; P < .003) or smoking discussions (31% v 41%, respectively; P <
      .05). Cervical cancer survivors were more likely than AWCs of similar age range
      to discuss smoking (58% v 43%, respectively; P < .001). CONCLUSION: Findings from
      this nationally representative sample suggest that many providers may miss
      opportunities to counsel survivors about healthy behaviors, perhaps particularly
      colorectal cancer survivors.

PMID- 17513817
TI  - Imaging in local staging of gastric cancer: a systematic review.
AB  - PURPOSE: Endoscopic ultrasound (EUS) has been established as the diagnostic
      modality of choice in local (T) staging of gastric cancer. Multidetector row
      computed tomography (MDCT) and magnetic resonance imaging (MRI) are promising
      alternatives. The aim of this study was to systematically review the literature
      regarding the performance of each of these imaging modalities. METHODS: A
      systematic search for relevant studies was performed in the PubMed/MEDLINE and
      EMBASE databases. Two reviewers independently assessed the methodological quality
      of each study. Local staging performance of included studies was calculated.
      RESULTS: Twenty-two EUS studies, five MDCT studies, one combined EUS and MDCT
      study, and three MRI studies met the inclusion criteria. The studies were of
      moderate methodological quality. Diagnostic accuracy of overall T staging for
      EUS, MDCT, and MRI varied between 65% to 92.1%, 77.1% to 88.9%, and 71.4% to
      82.6%, respectively. Sensitivity for assessing serosal involvement for EUS, MDCT,
      and MRI varied between 77.8% to 100%, 82.8% to 100%, and 89.5% to 93.1%,
      respectively. Specificity for assessing serosal involvement for EUS, MDCT, and
      MRI varied between 67.9% to 100%, 80% to 96.8%, and 91.4% to 100%, respectively.
      CONCLUSION: EUS, MDCT, and MRI achieve similar results in terms of diagnostic
      accuracy in T staging and in assessing serosal involvement. Most experience has
      been gained with EUS. Few MDCT studies and even fewer MRI studies are available.
      Thus, EUS remains the first-choice imaging modality in preoperative T staging of
      gastric cancer.

PMID- 17513815
TI  - Impact of a peer-delivered telephone intervention for women experiencing a breast
      cancer recurrence.
AB  - PURPOSE: A first breast cancer recurrence creates considerable distress, yet few
      psychosocial interventions directed at this population have been reported. The
      Southwest Oncology Group conducted a phase III randomized trial to evaluate the
      effectiveness of a brief telephone intervention. PATIENTS AND METHODS: Three
      hundred five women experiencing a first recurrence of breast cancer were randomly
      assigned to standard care or intervention. The intervention consisted of four to
      eight telephone calls delivered over a 1-month period. The calls were conducted
      by trained peer counselors at a breast cancer advocacy organization, the Y-ME
      National Breast Cancer Organization, and followed a standard curriculum.
      Psychosocial distress (Cancer Rehabilitation Evaluation System-Short Form [CARES
      SF]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale
      [CES-D]) outcomes were assessed at baseline and 3 and 6 months. The 3-month
      assessment was the primary end point and is the focus of this article. RESULTS:
      Analysis revealed no differences in distress or depressive symptoms at 3 months
      between the intervention and control groups; at 3 months, 70% of control patients
      and 66% of intervention patients reported psychosocial distress, and 40% of
      control patients and 47% of intervention patients exhibited depressive symptoms.
      CONCLUSION: Telephone peer counseling did not lead to better psychosocial
      outcomes. The persistent distress in these women supports the urgent need for the
      development and testing of more intensive or different supportive interventions
      for this group of patients.

PMID- 17513818
TI  - Aggregating and partitioning populations in health care disparities research:
      differences in perspective.
AB  - Health and health care are distributed unevenly across individuals and
      populations, and identifying these disparities is the first step toward remedying
      them. We reveal how conceptual and statistical challenges make even the
      identification of disparities difficult. These difficulties arise because the
      social, biologic, and environmental causes of disparities are intertwined,
      leading to statistical confounding. These difficulties arise also because the
      same data can be analyzed to examine care from the perspective of the patient, or
      from the perspective of organizations such as health systems or jurisdictions,
      and these alternative perspectives can yield contradictory results. The result is
      that health care disparities can be challenging to interpret unless the analytic
      and policy perspective is clear.

PMID- 17513819
TI  - Proposal for the use of progression-free survival in unblinded randomized trials.
AB  - Progression-free survival is an attractive end point for clinical trials when an
      overall survival end point may be confounded by additional treatments
      administered after progression. When a trial is performed in an unblinded manner,
      however, there is the potential for bias between the treatment arms because of
      the subjective aspects of the progression end point. We discuss the magnitude of
      this potential bias and suggest methods for lessening it. We propose the carrying
      forward of any progression information to two designated time points for the
      statistical analysis for trials that are not blinded. This proposal, possibly
      combined with central review of progression scans for these two time points,
      essentially eliminates any bias, with little risk of major efficiency loss
      compared with using the reported progression times.

PMID- 17513820
TI  - Proposal for standardized definitions for efficacy end points in adjuvant breast
      cancer trials: the STEEP system.
AB  - PURPOSE: Standardized definitions of breast cancer clinical trial end points must
      be adopted to permit the consistent interpretation and analysis of breast cancer
      clinical trials and to facilitate cross-trial comparisons and meta-analyses.
      Standardizing terms will allow for uniformity in data collection across studies,
      which will optimize clinical trial utility and efficiency. A given end point term
      (eg, overall survival) used in a breast cancer trial should always encompass the
      same set of events (eg, death attributable to breast cancer, death attributable
      to cause other than breast cancer, death from unknown cause), and, in turn, each
      event within that end point should be commonly defined across end points and
      studies. METHODS: A panel of experts in breast cancer clinical trials
      representing medical oncology, biostatistics, and correlative science convened to
      formulate standard definitions and address the confusion that nonstandard
      definitions of widely used end point terms for a breast cancer clinical trial can
      generate. We propose standard definitions for efficacy end points and events in
      early-stage adjuvant breast cancer clinical trials. In some cases, it is expected
      that the standard end points may not address a specific trial question, so that
      modified or customized end points would need to be prospectively defined and
      consistently used. CONCLUSION: The use of the proposed common end point
      definitions will facilitate interpretation of trial outcomes. This approach may
      be adopted to develop standard outcome definitions for use in trials involving
      other cancer sites.

PMID- 17513821
TI  - Pleural mesothelioma metastatic to tongue.

PMID- 17513822
TI  - Pancreatic glucagonoma presenting as necrolytic migratory erythema.

PMID- 17513823
TI  - Pulmonary intravascular large B-cell lymphoma as a cause of severe hypoxemia.

PMID- 17513824
TI  - Temporal dependence of the effect of radiation on erlotinib-induced skin rash.

PMID- 17513825
TI  - Communicating with patients about chemotherapy costs.

PMID- 17513826
TI  - PACS 01 trial: questions about patients' characteristics and reported results.

PMID- 17513827
TI  - EGFR expression and mutational analysis as a predictive test.

PMID- 17513828
TI  - Increased importance of intravenous iron in chemotherapy-induced anemia.

PMID- 17513829
TI  - Induction chemoradiotherapy for superior sulcus non-small-cell lung cancer: an
      answer for few.

PMID- 17513830
TI  - Letrozole compared with tamoxifen as initial adjuvant therapy for breast cancer.

PMID- 17513832
TI  - 'Oh pick me, pick me'--selecting participants for xenotransplant clinical trials.

PMID- 17513831
TI  - Transcription factor modularity in a gene-centered C. elegans core neuronal
      protein-DNA interaction network.
AB  - Transcription regulatory networks play a pivotal role in the development,
      function, and pathology of metazoan organisms. Such networks are comprised of
      protein-DNA interactions between transcription factors (TFs) and their target
      genes. An important question pertains to how the architecture of such networks
      relates to network functionality. Here, we show that a Caenorhabditis elegans
      core neuronal protein-DNA interaction network is organized into two TF modules.
      These modules contain TFs that bind to a relatively small number of target genes
      and are more systems specific than the TF hubs that connect the modules. Each
      module relates to different functional aspects of the network. One module
      contains TFs involved in reproduction and target genes that are expressed in
      neurons as well as in other tissues. The second module is enriched for paired
      homeodomain TFs and connects to target genes that are often exclusively neuronal.
      We find that paired homeodomain TFs are specifically expressed in C. elegans and
      mouse neurons, indicating that the neuronal function of paired homeodomains is
      evolutionarily conserved. Taken together, we show that a core neuronal C. elegans
      protein-DNA interaction network possesses TF modules that relate to different
      functional aspects of the complete network.

PMID- 17513833
TI  - Comparison of the effects of thiopentone and propofol on the electrocardiogram of
      dogs.
AB  - Sixty-four dogs were randomly assigned to receive either thiopentone or propofol
      and their electrocardiograms were recorded immediately before and shortly after
      they were anaesthetised. Thiopentone caused a marked increase in QT and JT
      intervals, a flattening of the T-wave and an increase in precordial QT
      dispersion. Propofol induced a less marked increase in QT and JT intervals,
      corrected for heart rate. Both agents induced an increase in heart rate and a
      decrease in heart rate variability, consistent with reduced vagal tone. Shortly
      after anaesthesia was induced, thiopentone affected ventricular repolarisation to
      a far greater extent than propofol, changes which suggest that it may be more
      likely to induce re-entrant ventricular arrhythmogenesis and could be associated
      with an increase in sympathetic tone. Propofol may therefore be more suitable
      than thiopentone for dogs with a susceptibility to ventricular arrhythmias or a
      long QT interval.

PMID- 17513834
TI  - Evidence of indirect transmission of classical swine fever virus through contacts
      with people.
AB  - A strict system for visiting experimentally inoculated and susceptible weaner
      pigs was used to examine the potential indirect transmission of classical swine
      fever (CSF) virus by people wearing contaminated boots, gloves and coveralls. The
      inoculated and susceptible pigs were housed in separate compartments, between
      which the airborne transmission of the virus was impossible. A worst-case
      scenario with an intensive visiting protocol and no form of disinfection or
      hygiene was established. Fifteen days after the pigs were inoculated, infection
      was detected in one contact pig, and it was concluded that under the conditions
      of the experiment CSF virus could be transmitted by contact with people.

PMID- 17513835
TI  - Some factors affecting the accuracy and variability of measurements of the height
      of ponies.
AB  - Height is the only factor used to differentiate horses and ponies for competitive
      purposes; any horse without shoes that is less than 148 cm at the highest point
      of the withers can be classified as a pony. However, variations in height
      associated with anatomical and other factors can occur. In this study the
      accuracy of the most commonly used measuring procedure and seven independent
      factors that might affect apparent height were evaluated in skeletally mature
      horses that were less than 155 cm in height. The results indicated that there was
      an improvement of 57 per cent in the accuracy of measurement when a second spirit
      level was added to the traditional measuring stick. The spread of values recorded
      for a series of repeated measurements by one person was +/-1.06 cm, but the
      spread increased to +/-1.89 cm when three different people made the measurements.
      Some variation in height occurred when the position of the pony's head was
      changed, but none occurred after a period of exercise. There was a reduction in
      height of 0.84 cm when the animals were allowed to adapt to their surroundings,
      and there was some reduction after they had been tranquillised.

PMID- 17513836
TI  - Molecular typing of a new foot-and-mouth disease virus in Egypt.

PMID- 17513837
TI  - Neurological signs associated with aflatoxicosis in Piedmontese calves.

PMID- 17513838
TI  - Intestinal helminths of dogs in northern Japan.

PMID- 17513839
TI  - Occurrence of vancomycin-resistant enterococci in chickens in Malaysia.

PMID- 17513840
TI  - BVD virus type 2 infection and severe clinical disease in a dairy herd.

PMID- 17513841
TI  - Voicing the profession's concerns.

PMID- 17513842
TI  - Arthrotomy and arthrodesis of the fetlock joint in cattle.

PMID- 17513843
TI  - Canine blood donors.

PMID- 17513844
TI  - Difficulties facing new graduates.

PMID- 17513845
TI  - Withdrawal of routine brucellosis testing in beef herds.

PMID- 17513847
TI  - An evaluation of a state hepatitis prevention and control program: focus group
      interviews with clients.
AB  - This article presents the results of the qualitative component of a comprehensive
      evaluation of a state hepatitis prevention and control program. The qualitative
      component of the evaluation was designed to assess the motivational factors
      behind clients seeking hepatitis-related services and explore their experiences
      with the services provided by local health departments. The transtheoretical
      model was employed as a means of identifying the stage of change the client was
      in and what processes of change were useful in moving the client through the
      various stages of change. Focus groups were conducted with 44 participants in six
      different counties in Florida. Results of the focus group interviews support the
      use of the transtheoretical model in program evaluation using focus group
      methods. The findings of the focus groups suggest the need for education of the
      public and health care providers regarding hepatitis and the importance of
      supportive relationships to clients seeking and receiving hepatitis screening and
      vaccination.

PMID- 17513850
TI  - Purification of antimicrobial factors from human cervical mucus.
AB  - BACKGROUND: The aim of this study was to separate bactericidal proteins from
      healthy female cervical mucus. METHODS: Cervical mucus was collected and
      dissolved in 1% acetic acid. The antimicrobial activity of acid-soluble extracts
      was detected by gel overlay assay against Escherichia coli ATCC 43827. The
      extracts showed considerable amount of antibacterial activity with a clearly
      visible band. The bactericidal band was purified by reverse-phase high
      performance liquid chromatography and the antibacterial activity of the eluate
      was examined using radial diffusion assay. RESULTS: Two antimicrobial proteins
      were purified and were further characterized by Tricine sodium dodecyl sulphate
      polyacrylamide gel electrophoresis, N-terminal sequencing and matrix-assisted
      laser desorption ionization time-of-flight mass spectrometry. The proteins were
      identified as high-mobility group nucleosomal-binding domain 2 (HMG N2) and
      secretory leukocyte peptidase inhibitor (SLPI). SLPI is an antimicrobial peptide
      already known in the cervical mucus while HMG N2 in the cervical mucus had not
      been previously reported. The expression of HMG N2 mRNA was detected in Hela
      cells and cervical epithelial cells by RT-PCR. Slit hybridization showed abundant
      amounts of the HMG N2 protein in the cervical mucus. CONCLUSIONS: These results
      suggest that the expression of HMG N2 and SLPI in the healthy female cervical
      mucus may be relevant to their immune surveillance and defense against potential
      pathogens in human reproductive system.

PMID- 17513849
TI  - Quantitative profile of the uropathogenic Escherichia coli outer membrane
      proteome during growth in human urine.
AB  - Outer membrane proteins (OMPs) of microbial pathogens are critical components
      that mediate direct interactions between microbes and their surrounding
      environment. Consequently, the study of OMPs is integral to furthering the
      understanding of host-pathogen interactions and to identifying key targets for
      development of improved antimicrobial agents and vaccines. In this study, we used
      two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and tandem mass
      spectrometry to characterize the uropathogenic Escherichia coli (UPEC) outer
      membrane subproteome; 30 individual OMPs present on the bacterial surface during
      growth in human urine were identified. Fluorescence difference gel
      electrophoresis was used to identify quantitative changes in levels of UPEC
      strain CFT073 OMPs during growth in urine; six known receptors for iron compounds
      were induced in this environment, i.e., ChuA, IutA, FhuA, IroN, IreA, and Iha. A
      seventh putative iron compound receptor, encoded by CFT073 open reading frame
      (ORF) c2482, was also identified and found to be induced in urine. Further, the
      induction of these seven iron receptors in human urine and during defined iron
      limitation was verified by using quantitative real-time PCR (qPCR). An eighth
      iron receptor, fepA, displayed similar induction levels under these conditions as
      measured by qPCR but was not identified by 2D-PAGE. Addition of 10 microM FeCl(2)
      to human urine repressed the transcription of all eight iron receptor genes. A
      number of fecal-commensal, intestinal pathogenic, and uropathogenic E. coli
      strains all displayed similar growth rates in human urine, showing that the
      ability to grow in urine per se is not a urovirulence trait. Thus, human urine is
      an iron-limiting environment and UPEC enriches its outer membrane with iron
      receptors to contend with this iron limitation.

PMID- 17513851
TI  - Monte-Carlo study of energy deposition by heavy charged particles in sub-cellular
      volumes.
AB  - Detailed-history Monte-Carlo code is used to study the energy deposition from
      proton and alpha particle tracks at the sub-cellular level. Inelastic cross
      sections for both the vapour and liquid phases of water have been implemented
      into the code in order to explore the influence of non-linear density effects
      associated with the condensed-phase cellular environment. Results of energy
      deposition and its straggling for 0.5 to 5 MeV amu(-1) protons and alpha
      particles traversing or passing near spherical volumes of 2-200 nm in diameter
      relevant to DNA- and chromosome-size targets are presented. It is shown that the
      explicit account of delta-ray transport reduces the dose by as much as 10-60%,
      whereas stochastic fluctuations lead to a relative uncertainty ranging from 20%
      to more than 100%. Protons and alpha particles of the same velocity exhibit a
      similar delta-ray effect, whereas the relative uncertainty of the alphas is
      almost half that of protons. The effect of the phase is noticeable (10-15%)
      mainly through differences on the transport of delta-rays, which in liquid water
      have higher penetration distances. It is expected that the implementation of such
      results into multi-scale biophysical models of radiation effects will lead to a
      more realistic predictions on the efficacy of new radiotherapeutic modalities
      that employ either external proton beam irradiation or internal alpha-emitting
      radionuclides.

PMID- 17513852
TI  - Monte Carlo calculations and validation of a gold foil-based Bonner sphere
      system.
AB  - The Grup de Fisica de les Radiacions (GFR) of the Universitat Autonoma de
      Barcelona (UAB), in collaboration with the Institute for Radiological Protection
      and Nuclear Safety (IRSN), has developed a passive Bonner sphere system (UAB
      BSS), with gold foils as thermal neutron detectors, for application in pulsed
      neutron fields or in mixed neutron-photon fields with high photon intensities. In
      such fields, active devices suffer from saturation and dead-time effects. The
      MCNPX Monte-Carlo code has been used to determine the response to neutrons of
      different energies of each polyethylene sphere belonging to the BSS. The passive
      UAB-BSS system was characterised with the ISO (252)Cf reference source at the
      IRSN facilities. The energy distribution of the reference source neutron fluence
      was folded with the response functions for comparison with the experimental data.
      A good agreement between the experimental and calculated count rates was found.

PMID- 17513853
TI  - Method for determination of gamma and neutron dose components in mixed radiation
      fields using a high-pressure recombination chamber.
AB  - A new method is proposed for the determination of dose components in mixed
      radiation fields (gamma + neutrons) using a recombination chamber. The method
      involves the determination of the ratio of ionisation currents measured at two
      different voltages applied to the chamber without the need of determining the
      saturation current, neither in the radiation field investigated nor during
      calibration. Therefore, the chamber can be filled with a gas under a pressure
      much higher than that used in presently available recombination chambers. This
      paper presents theoretically derived formulae supporting the method and the
      experimental results of dose component measurements using a high-pressure
      recombination chamber filled with methane. The method can be used for determining
      neutron and gamma dose components in the environment, especially in the vicinity
      of nuclear centres.

PMID- 17513854
TI  - Ionisation density effects following optical excitation in LiF:Mg, Ti (TLD-100).
AB  - The TL signal following 5 eV photon excitation of previously irradiated and
      readout material has been studied as a function of ionisation density and various
      experimental parameters: (i) maximum temperature of the first readout; (ii)
      photon fluence; (iii) photon energy and (iv) beta ray dose. Following alpha
      particle irradiation, the ratio of the second-readout to first-readout TL signal,
      epsilon(alpha,) has been found to be 10-20 times higher than that following beta
      irradiation, indicative of the possibility of using the double ratio
      epsilon(alpha)/epsilon(beta) as a mixed-field discriminator. The beginning of an
      attempt to explain this unusual effect is offered in the framework of the track
      structure theory and kinetic modelling of the beta ray dose-response of the first
      and second readouts.

PMID- 17513855
TI  - Radionuclide neutron sources in calibration laboratory--neutron and gamma doses
      and their changes in time.
AB  - The calibration laboratory, having standard neutron fields of radionuclide
      sources, should perform regular measurements of fields' parameters in order to
      check their stability and to get knowledge of any changes. Usually, accompanying
      gamma radiation is not of serious concern, but some personal dosemeters, old
      neutron dose equivalent meters with scintillation detectors and the dose meters
      of mixed radiation require the determination of this component. In the Laboratory
      of Radiation Protection Measurements in the Institute of Atomic Energy, Poland,
      the fields of radionuclide neutron sources (252)Cf, (241)Am-Be and (239)Pu-Be
      were examined for nearly 20 y. A number of detectors and methods have been
      applied for the determination of neutron ambient dose equivalent rate and for the
      determination of neutron and gamma dose components. This paper presents the
      recent results of measurements of gamma and neutron dose and dose equivalent,
      compared with the results accumulated in nearly 20 y.

PMID- 17513856
TI  - Neutron fluence rate measurement using prompt gamma rays.
AB  - A gamma ray spectrometer, with a 3('') O X 3('') NaI(Tl) detector, with a
      moderator sphere has been utilised to measure the neutron fluence rate, with this
      value the H(10) was estimated. When a neutron is captured by the hydrogen-based
      moderator, a 2.22 MeV prompt gamma ray is produced. In a multichannel analyser
      the net area under the 2.22 MeV photopeak is proportional to the total neutron
      fluence rate. The features of this system were determined by a Monte Carlo study
      that includes 3-, 5- and 10-inches diameter, water and polyethylene moderators
      and a (239)Pu-Be source. The prompt gamma response was extended to monoenergetic
      neutron sources. To verify the response, a (239)Pu-Be source in combination with
      a 10('') polyethylene sphere having a gamma-ray spectrometer with NaI(Tl) was
      utilised to estimate the neutron fluence rate and the H(10). These results were
      compared with neutron fluence rate and H(10) obtained using a Bonner sphere
      spectrometer and with the H(10) measured using a neutron remmeter.

PMID- 17513857
TI  - Characterisation of kilo electron volt neutron fluence standard with the
      45Sc(p,n)45Ti reaction at NMIJ.
AB  - We are developing a national standard of a monoenergetic kilo electron volt
      neutron field with the (45)Sc(p,n)(45)Ti resonance reaction. A wide resonance
      yields 27.4 keV neutrons at 0 degrees with respect to the proton beam. The proton
      energy was precisely determined in the measurement of the relative neutron yield
      as a function of the proton energy from the threshold energy to 2.942 MeV.
      Absolute measurement of the monoenergetic neutron fluence was performed using a
      (3)He proportional counter. Relative measurement was also carried out using a
      Bonner sphere calibrated at our 144 keV standard neutron field. Calibration
      factors were obtained between the count of a neutron monitor and the neutron
      fluence. A silicon-surface barrier detector with a (6)LiF foil converter was also
      being developed for the neutron fluence measurement. Successful results were
      obtained in the tests in the 144 keV standard neutron field.

PMID- 17513858
TI  - Modelling and calculations of the response of tissue equivalent proportional
      counter to charged particles.
AB  - Space activities in earth orbit or in deep space pose challenges to the
      estimation of risk factors for both astronauts and instrumentation. In space,
      risk from exposure to ionising radiation is one of the main factors limiting
      manned space exploration. Therefore, characterising the radiation environment in
      terms of the types of radiations and the quantity of radiation that the
      astronauts are exposed to is of critical importance in planning space missions.
      In this paper, calculations of the response of TEPC to protons and carbon ions
      were reported. The calculations have been carried out using Monte Carlo track
      structure simulation codes for the walled and the wall-less TEPC counters. The
      model simulates nonhomogenous tracks in the sensitive volume of the counter and
      accounts for direct and indirect events. Calculated frequency- and dose-averaged
      lineal energies 0.3 MeV-1 GeV protons are presented and compared with the
      experimental data. The calculation of quality factors (QF) were made using
      individual track histories. Additionally, calculations of absolute frequencies of
      energy depositions in cylindrical targets, 100 nm height by 100 nm diameter, when
      randomly positioned and oriented in water irradiated with 1 Gy of protons of
      energy 0.3-100 MeV, is presented. The distributions show the clustering
      properties of protons of different energies in a 100 nm by 100 nm cylinder.

PMID- 17513859
TI  - Optimisation of the readout parameters when evaluating thermal neutron doses by
      TL dosimetry with LiF:Mg,Ti.
AB  - The location of the glow peaks depends on the heating rate. It takes some time
      until the crystal reaches the heater temperature, and this time lag has a direct
      effect on the shift of peaks towards higher temperatures. Some information on the
      high-temperature peaks may be lost if the readout conditions (mainly length of
      time) are not properly chosen. Step heating profiles to a varying final
      temperature between 300 degrees C and 125 degrees C were used to study the time
      dependence of the collected information in the glow curves of (6)LiF:Mg,Ti
      crystals, and the minimal heating time for evaluation of thermal neutron doses
      was determined.

PMID- 17513860
TI  - Set-up of a passive Bonner sphere system for neutron spectrometry at mixed fields
      with predominant photon component based on activation detector.
AB  - A passive Bonner sphere system (BSS), based on thermal neutron activation
      detectors, was developed to perform neutron spectrometry in pulsed and very
      intense (n-gamma) fields with predominant photon component, as those produced by
      high energy (>10 MV) medical linear electron accelerators. In this paper, a
      description of the new system is presented together with an experimental
      characterisation of a portable Sodium Iodide (NaI) detector and a fixed high
      purity Germanium one, both used to measure the induced gamma-activity of the
      activated materials, respectively, in situ and in the laboratory. The choice of
      the activated materials is justified according to pre-established practical
      considerations and physical criteria. The response functions of the entire
      passive BSS were calculated using the MCNPX code. A preliminary experimental
      validation with a bare (252)Cf source is given as well.

PMID- 17513861
TI  - The determination of a neutron source position in an unknown homogeneous medium;
      the 3D case.
AB  - The possibility of localisation of an unknown neutron source in various bulky
      homogeneous media (box) was studied. Previous study showed that for the planar
      case, neutron source could be localised with accuracy better than 7%, by using
      the count rates ratio of two (3)He detectors, positioned on the opposite faces of
      the box. The influence of the deviation of the source from the virtual plane
      connecting the two (3)He detectors was studied. It was found that for detectors
      placed on the centres of the sample faces, larger distance of the source from the
      central line leads to larger error, up to 15%. It was found that while using the
      measurement of the ratio R(0) of external source placed on the box face coplanar
      with unknown source, accuracy does not depend on the distance from central line.
      Different ways to determine the plane of the unknown source were investigated. It
      was found that it is impossible to determine it by looking for maximum count rate
      of one detector or geometric mean of a pair of detectors. The experimental
      results were confirmed with Monte-Carlo N-particle (MCNP) simulations.

PMID- 17513862
TI  - Development of the fast neutron standard using a Be({alpha},n) reaction at the
      National Metrology Institute of Japan.
AB  - This paper describes the 8-MeV neutron field where the neutrons are generated in
      the (9)Be(alpha,n)(12)C reaction by bombardment of a beryllium target with a 2.4
      MeV (4)He(+) beam from a Van de Graaff accelerator. The neutron field is being
      prepared for a new national standard on neutron fluence in Japan. Absolute
      measurement of the neutron fluence was taken using a proton recoil neutron
      detector, consisting of a silicon surface barrier detector with a polyethylene
      radiator. Neutron spectra were measured using a newly developed recoil proton
      spectrometer and a liquid organic scintillation detector. The gamma rays existing
      in the field were also characterised using a liquid organic scintillation
      detector. The ambient dose equivalents of the gamma rays were estimated to be
      <100 microSv at the neutron fluence of 10(7) neutrons cm(-2).

PMID- 17513863
TI  - Gbetagamma-mediated prostacyclin production and cAMP-dependent protein kinase
      activation by endothelin-1 promotes vascular smooth muscle cell hypertrophy
      through inhibition of glycogen synthase kinase-3.
AB  - Endothelin-1 (ET1) is a vasoactive peptide that stimulates hypertrophy of
      vascular smooth muscle cells (VSMC) through diverse signaling pathways mediated
      by G(q)/G(i)/G(13) heterotrimeric G proteins. We have found that ET1 stimulates
      the activity of cAMP-dependent protein kinase (PKA) in VSMC as profoundly as the
      G(s)-linked beta-adrenergic agonist, isoproterenol (ISO), but in a transient
      manner. PKA activation by ET1 was mediated by type-A ET1 receptors (ETA) and
      recruited an autocrine signaling mechanism distinct from that of ISO, involving
      G(i)-coupled betagamma subunits of heterotrimeric G proteins, extracellular
      signal-regulated kinases ERK1/2, cyclooxygenase COX-1 (but not COX-2) and
      prostacyclin receptors. In the functional studies, inhibition of PKA or COX-1
      attenuated ET1-induced VSMC hypertrophy, suggesting the positive role of PKA in
      this response to ET1. Furthermore, we found that ET1 stimulates a Gbetagamma
      mediated, PKA-dependent phosphorylation and inactivation of glycogen synthase
      kinase-3 (GSK3), an enzyme that regulates cell growth. Together, this study
      describes that (i) PKA can be transiently activated by G(i)-coupled agonists such
      as ET1 by an autocrine mechanism involving Gbetagamma/calcium/ERK/COX
      1/prostacyclin signaling, and (ii) this PKA activation promotes VSMC hypertrophy,
      at least in part, through PKA-dependent phosphorylation and inhibition of GSK3.

PMID- 17513864
TI  - Identification of a minimal myosin Va binding site within an intrinsically
      unstructured domain of melanophilin.
AB  - Myosin V is a molecular motor that transports a variety of cellular cargo,
      including organelles, vesicles, and messenger RNA. The proper peripheral
      distribution of melanosomes, a dense pigment-containing organelle, is dependent
      on actin and the activity of myosin Va. The recruitment of myosin Va to the
      melanosome and proper transport of the melanosome requires melanophilin, which
      directly binds to myosin Va and is tethered to the melanosome membrane via
      Rab27a. Here we use highly purified proteins to demonstrate that the globular
      tail domain of myosin Va binds directly to an intrinsically unstructured domain
      of melanophilin. The myosin Va binding domain of melanophilin lacks stable
      secondary structure, and (1)H NMR measurements indicate that the protein is
      unfolded. This domain is extremely sensitive to mild proteolysis and has a
      hydrodynamic radius that is consistent with a random coil-like polypeptide. We
      show that myosin Va binding does not induce the global folding of melanophilin.
      Truncations of melanophilin were utilized to define a short peptide sequence (26
      residues) within melanophilin that is critical for myosin Va binding. We
      demonstrate that a peptide corresponding to these residues binds directly to the
      globular tail domain with the same affinity as melanophilin. We discuss the
      possible implications of protein intrinsic disorder in recruitment and
      maintenance of myosin Va on melanosome membranes.

PMID- 17513865
TI  - Transforming growth factor-beta1 induces an epithelial-to-mesenchymal transition
      state in mouse hepatocytes in vitro.
AB  - Liver fibrosis is a progressive pathologic process that involves deposition of
      excess extracellular matrix leading to distorted architecture and culminating in
      cirrhosis. The role of transforming growth factor-beta (TGF-beta) as a key
      molecule in the development and progression of hepatic fibrosis via the
      activation of hepatic stellate cells, among other fibroblast populations, is
      without controversy. We hereby show that TGF-beta1 induces an epithelial-to
      mesenchymal transition (EMT) state in mature hepatocytes in vitro. EMT state was
      marked by significant upregulation of alpha(1)(I) collagen mRNA expression and
      type I collagen deposition. Similar changes were found in a "normal" mouse
      hepatocyte cell line (AML12), thus confirming that hepatocytes are capable of EMT
      changes and type I collagen synthesis. We also show that in hepatocytes in the
      EMT state, TGF-beta1 induces the snail-1 transcription factor and activates the
      Smad2/3 pathway. Evidence for a central role of the TGF-beta1/Smad pathway is
      further supported by the inhibition of EMT by Smad4 silencing using small
      interference RNA technology. In conclusion, TGF-beta1, a known pro-apoptotic
      cytokine in mature hepatocytes, is capable of mediating phenotypic changes and
      plasticity in the form of EMT, resulting in collagen deposition. Our findings
      support a potentially crucial role for EMT in the development and progression of
      hepatic fibrogenesis.

PMID- 17513866
TI  - Identification of essential catalytic residues of the cyclase NisC involved in
      the biosynthesis of nisin.
AB  - Nisin is a post-translationally modified antimicrobial peptide that has been
      widely used in the food industry for several decades. It contains five cyclic
      thioether cross-links of varying sizes that are installed by a single enzyme,
      NisC, that catalyzes the addition of cysteines to dehydroamino acids. The recent
      x-ray crystal structure of NisC has provided the first insights into the
      catalytic residues responsible for the cyclization step during nisin
      biosynthesis. In this study, the conserved residues His(212), Arg(280), Asp(141),
      and Tyr(285) as well as the ligands to the zinc in the active site (Cys(284),
      Cys(330), and His(331)) were substituted by site-directed mutagenesis. Binding
      studies showed that all mutants had similar affinities for NisA. Activity assays
      showed that whereas His(212) and Asp(141) were essential for correct cyclization
      as judged by the antimicrobial activity of the final product, Arg(280) and
      Tyr(285) were not. Mutation of zinc ligands to alanine also abolished the
      enzymatic activity, and these mutant proteins were shown to contain decreased
      levels of zinc. These results show that the zinc is essential for activity and
      support a model in which the zinc is used to activate the cysteines in the
      substrate for nucleophilic attack. These findings also argue against an essential
      role of Arg(280) and Tyr(285) as an active site general acid/base in the
      mechanism of cyclization.

PMID- 17513867
TI  - Forkhead proteins are critical for bone morphogenetic protein-2 regulation and
      anti-tumor activity of resveratrol.
AB  - Osteoporosis is a major public health problem and the most obvious preventive
      strategy, hormone replacement therapy, has lost favor due to recent findings of
      the Women's Health Initiative regarding increased risks of breast cancer and
      cardiovascular disease. Resveratrol, a naturally occurring compound possessing
      estrogenic activity, is thought to have considerable potential for therapy of
      osteoporosis. In the present study, resveratrol was found to exhibit bone
      protective effects equivalent to those exerted by hormone replacement therapy and
      decrease the risk of breast cancer in the in vivo and in vitro models. Forkhead
      proteins were found to be essential for both effects of resveratrol. The bone
      protective effect was attributable to induction of bone morphogenetic protein-2
      through Src kinase-dependent estrogen receptor activation and FOXA1 is required
      for resveratrol-induced estrogen receptor-dependent bone morphogenetic protein-2
      expression. The tumor-suppressive effects of resveratrol were the consequence of
      Akt inactivation-mediated FOXO3a nuclear accumulation and activation. Resveratrol
      is therefore anticipated to be highly effective in management of postmenopausal
      osteoporosis without an increased risk of breast cancer.

PMID- 17513869
TI  - Morphology and anatomy of physical dormancy in Ipomoea lacunosa: identification
      of the water gap in seeds of Convolvulaceae (Solanales).
AB  - BACKGROUND AND AIMS: Convolvulaceae is the most advanced plant family (asterid
      clade) that produces seeds with physical dormancy (water-impermeable seed coat).
      There are several different opinions about the nature of the specialized
      structure ('water gap') in the seed coat through which water initially enters
      seeds of Convolvulaceae, but none of them has been documented clearly. The
      primary aim of the study was to identify the water gap in seeds of Ipomoea
      lacunosa (Convolvulaceae) and to describe its morphology, anatomy and function.
      METHODS: Light microscopy, scanning electron microscopy, tissue-sectioning, dye
      tracking and blocking experiments were used to describe the morphology, anatomy
      and function of the water gap in seeds of I. lacunosa. KEY RESULTS: Dormancy
      breaking treatments caused slits to form around the two bulges on the seed coat
      adjacent to the hilum, and dye entered the seed only via the disrupted bulges.
      Bulge anatomy differs from that of the rest of the seed coat. Sclereid cells of
      the bulges are more compacted and elongated than those in the hilum pad and in
      the rest of the seed coat away from the bulges. CONCLUSIONS: The transition area
      between elongated and square-shaped sclereid cells is the place where the water
      gap opens. Morphology/anatomy of the water gap in Convolvulaceae differs from
      that of taxa in the other 11 angiosperm plant families that produce seeds with
      physical dormancy for which it has been described.

PMID- 17513868
TI  - MMP25 (MT6-MMP) is highly expressed in human colon cancer, promotes tumor growth,
      and exhibits unique biochemical properties.
AB  - MMP25 (MT6-MMP) is one of the two glycosylphosphatidylinositol-anchored matrix
      metalloproteinases (MMPs) that have been suggested to play a role in pericellular
      proteolysis. However, its role in cancer is unknown, and its biochemical
      properties are not well established. Here we found a marked increase in MT6-MMP
      expression within in situ dysplasia and invasive cancer in 61 samples of human
      colon cancer. Expression of MT6-MMP in HCT-116 human colon cancer cells promoted
      tumori-genesis in nude mice. Histologically, the MT6-MMP-expressing tumors
      demonstrated an infiltrative leading edge in contrast to a rounded leading edge
      in vector control tumors. Biochemical and biosynthesis analyses revealed that MT6
      MMP displayed on the cell surface exists as a major form of 120 kDa that likely
      represents enzyme homodimers linked by disulfide bonds. Upon reduction, a single
      57-kDa active MT6-MMP was detected. Interestingly, neither membrane-anchored nor
      phosphatidylinositol-specific phospholipase C-released MT6-MMPs were found to be
      associated with tissue inhibitor of metalloproteinases (TIMPs) and did not
      activate pro-gelatinases (pro-MMP-2 and pro-MMP-9) even in the presence of
      exogenous TIMP-2 or TIMP-1. A catalytic domain of MT6-MMP was inhibited
      preferentially by TIMP-1 (K(i) = 0.2 nm) over TIMP-2 (K(i) = 2.0 nm), because of
      a slower association rate. These results show that MT6-MMP may play a role in
      colon cancer and exhibit unique biochemical and structural properties that may
      regulate proteolytic function at the cell surface.

PMID- 17513870
TI  - Genetic diversity in Nothofagus alessandrii (Fagaceae), an endangered endemic
      tree species of the coastal maulino forest of Central Chile.
AB  - BACKGROUND AND AIMS: The endemic tree Nothofagus alessandrii (Fagaceae) has been
      historically restricted to the coastal range of Region VII of central Chile, and
      its forests have been increasingly destroyed and fragmented since the end of the
      19th century. In this study, the patterns of within- and among-population genetic
      diversity in seven fragments of this endangered narrowly endemic tree were
      examined. METHODS: Allozyme electrophoresis of seven loci of N. alessandrii was
      used to estimate genetic diversity, genetic structure and gene flow. KEY RESULTS:
      High levels of genetic diversity were found as shown by mean expected
      heterozygosity (H(e) = 0.182 +/- 0.034), percentage of polymorphic loci (P(p) =
      61.2 %), mean number of alleles per locus (A = 1.8) and mean number of alleles
      per polymorphic locus (A(p) = 2.3). Genetic differentiation was also high (G(ST)
      = 0.257 and Nm = 0.7). These values are high compared with more widespread
      congeneric species. CONCLUSIONS: Despite its endemic status and restricted
      geographical range N. alessandrii showed high levels of genetic diversity. The
      observed patterns of diversity are explained in part by historical processes and
      more recent human fragmentation.

PMID- 17513871
TI  - Dealing with incomplete and inaccurate data in public health: case study of a
      health equity audit of health visiting services.

PMID- 17513872
TI  - The slippery slope to sperm smuggling: prisoners, artificial insemination and
      human rights.

PMID- 17513873
TI  - Influence of fibre and filler reinforcement of plastic brackets: an in vitro
      study.
AB  - In spite of their popularity in fulfilling aesthetic requirements, plastic
      brackets still present some disadvantages because of their low elastic modulus,
      decreased fracture toughness, and reduced wear resistance. Fibre-reinforced
      composites are well established in dentistry and consist of a polymer matrix in
      which reinforcing fibres are embedded. Stress is transferred from the polymer
      matrix to the fibres which present a high tensile strength. Hence, the mechanical
      properties of polymers could be improved. The purpose of this study was to
      compare fracture strength, fracture toughness and flexural strength of an
      experimental fibre-reinforced bracket material, an SiO(2) filler-reinforced
      bracket and an unfilled plastic bracket material (control group). Experimental
      brackets and specialized bars were manufactured. Tests were performed after
      thermal cycling (5 degrees C/55 degrees C) the samples in an artificial oral
      environment of a device to simulate mastication. Statistical evaluation was
      undertaken. The median, 25th and 75th percentiles were calculated and a Mann
      Whitney U-test was performed. In this study two findings were obvious. (1) Filler
      reinforcement of plastic brackets improved fracture strength and fracture
      toughness in comparison with the unfilled bracket material. (2) Glass fibre
      reinforcement of orthodontic bracket materials resulted in the greatest
      enhancement of the mechanical properties in comparison with the other test
      groups. Therefore, the application of glass fibres in plastic brackets is a
      successful method to enhance fracture strength.

PMID- 17513874
TI  - Differences between high- and low-angle subjects in arch form and anterior
      crowding from 23 to 33 years of age.
AB  - The aim of this study was to compare changes in arch width and length in high-
      and low-angle subjects. The material comprised the cephalograms and study models
      of 17 males and 15 females with a high-angle and 12 males and 16 low-angle
      females. The age of the subjects at the first examination (T1) was 22 years 10
      months and 22 years 8 months in the high-angle groups, 22 years 5 months and 22
      years 8 months in the low-angle subjects, respectively, for males and females.
      The second assessment (T2) was 10 years and 9 years 10 months later in the high
      angle and, 10 years 3 months and 9 years 10 months in the low-angle groups,
      respectively. Statistical analysis of changes for each group during the
      observation period T1-T2 was undertaken using a paired t-test, and the
      differences between the groups with two-sample t-tests. The findings showed a
      general reduction in upper and lower arch length, an increase of intermolar
      width, and a decrease of intercanine width in both genders. Anterior perimeter
      and anterior space in both angles decreased in both males and females. The mean
      changes were small, but with large individual differences. There were no
      significant differences between the genders or the high- and low-angle groups in
      the changes, except that the female high-angle group had a statistically
      significant (P = 0.05) greater decrease in mandibular arch length than the low
      angle female group.

PMID- 17513875
TI  - Quantitative evaluation of lip symmetry in skeletal asymmetry.
AB  - The objective of this study was to investigate whether skeletal mandibular
      asymmetry associated with unilateral and anterior crossbite will lead to lip
      asymmetry. The subjects were 26 females, 13 controls and 13 true skeletal
      asymmetric age-matched patients (24-50 years). The study group was diagnosed as
      asymmetric according to visual and panoramic radiographic examination and
      exhibited a unilateral anterior crossbite, an asymmetric mandible, and a
      deviation of the chin. The control group was visually symmetric and exhibited all
      forms of tooth malalignment without the presence of a crossbite. Digitized images
      of the frontal facial photographs of all the subjects, taken in an intercuspal
      contact position, were analysed for upper and lower lip symmetry pre- and post
      orthodontic treatment. The upper and lower lips were subdivided into two
      quadrants each and the surface area of each quadrant was measured and expressed
      as a percentage of the total surface area of the relevant lip. The degree of lip
      asymmetry was obtained by calculating the difference in percentage area between
      the two quadrants of each lip. In the study group, the lower lip quadrant on the
      crossbite side was increased pre-treatment (56.85 +/- 1.75 per cent), while the
      contralateral side was reduced (43.15 +/- 1.75 per cent, P < 0.005), resulting in
      13.7 per cent asymmetry. After treatment, the respective lip areas were 52.12 +/-
      0.64 and 47.88 +/- 0.64 (P < 0.01) and asymmetry was significantly reduced (4.25
      +/- 1.29 per cent). In the control group, the differences between the lower lip
      quadrant areas (range 48.5-51.5 per cent) were small (less than 3 per cent
      asymmetry) and did not change post-treatment. The findings demonstrate that in
      this study group, lower lip symmetry was mainly controlled by the support
      provided through the dental interarch relationships and less by skeletal factors.

PMID- 17513876
TI  - Analysis of tooth movement in extraction cases using three-dimensional reverse
      engineering technology.
AB  - Despite inherent errors, cephalometric superimpositions are currently the most
      widely used means for assessing sagittal and vertical tooth movements. The
      purpose of this study was to compare three-dimensional (3D) digital model
      superimposition with cephalometric superimposition. The material was collected
      from initial and final maxillary casts and lateral cephalometric radiographs of
      30 patients (6 males, 24 females, mean age 17.7 years) who underwent orthodontic
      treatment with extraction of permanent teeth. Each pair of cephalograms was
      traced and superimposed according to Ricketts' four-step method. 3D scanning of
      the maxillary dental casts was performed using INUS dental scanning solution(R),
      which consists of a 3D scanner, an autoscan system, and 3D reverse modelling
      software. The 3D superimposition was carried out using the surface-to-surface
      matching (best-fit method) function of the autoscan system. The antero-posterior
      movement of the maxillary first molar and central incisor was evaluated
      cephalometrically and on 3D digital models. To determine whether any difference
      existed between the two measuring techniques, paired t-tests and correlation
      analysis were undertaken. The results revealed no statistical differences between
      the mean incisor and molar movements as assessed cephalometrically or by 3D model
      superimposition. These findings suggest that the 3D digital orthodontic model
      superimposition technique used in this study is clinically as reliable as
      cephalometric superimposition for assessing orthodontic tooth movements.

PMID- 17513877
TI  - The effect of a light-emitting diode on shear bond strength of ceramic brackets
      bonded to feldspathic porcelain with different curing times.
AB  - The aim of this study was to evaluate different curing times of a light-emitting
      diode (LED) unit on shear bond strength (SBS) of ceramic brackets bonded to
      feldspathic porcelain. Ceramic brackets were bonded with a light-cured adhesive
      to 96 feldspathic porcelain facets. Air-borne particle abrasion was performed
      using 25 mum aluminium trioxide (Al(2)O(3)) with an air abrasion device from a
      distance of approximately 10 mm at a pressure of 2.5 bars for 4 seconds, then the
      porcelain surfaces were etched with 9.6 per cent hydrofluoric acid for 2 minutes.
      After surface preparation of the porcelain specimens, silane was applied. In
      groups 1 and 2, the adhesive was cured with a quartz-tungsten-halogen (QTH) unit
      for 10 and 20 seconds, respectively. The LED was used in the standard mode for 3,
      5, and 10 seconds for groups 3, 4, and 5, respectively. For the other three
      groups, the LED was used in the fast mode for 3, 5, and 10 seconds, respectively.
      The SBS of the brackets was measured on a universal testing machine. The adhesive
      remnant index (ARI) scores, damage to the porcelain, and fracture of the ceramic
      bracket bases were determined. No significant differences were observed for SBS
      between the eight groups (P=0.087). There was no significant difference between
      the groups' ARI scores, porcelain damage, and bracket base fracture (P=0.340,
      P=0.985, and P=0.340, respectively). There was a greater frequency of ARI scores
      of 0 for all groups. Fifty per cent of the porcelain facets displayed damage.
      Nineteen ceramic bracket base fractures were observed. No significant difference
      was found for the SBS of the groups with QTH and LED units and curing times. It
      is reliable to use LED with a 3-second curing time since it provided adequate
      bond strength for ceramic brackets bonded to porcelain surfaces.

PMID- 17513878
TI  - A longitudinal study of craniofacial growth in idiopathic short stature and
      growth hormone-deficient boys treated with growth hormone.
AB  - The aim of this prospective, longitudinal, controlled study is to describe the
      long-term safety and efficacy of growth hormone (GH) administration on
      craniofacial morphology in boys with short stature. Forty-six boys, who started
      GH treatment at the Department of Paediatrics Goteborg Paediatric Growth Research
      Centre, were consecutively included in the study. Twenty-five boys were
      classified as growth hormone-deficient (GHD) and 21 as idiopathic short stature
      (ISS). The patients were injected with 33 (n=31) or 67 (n=15) microg GH/kg body
      weight/day. The mean age at the start of treatment was 11.8 years [standard
      deviation (SD) 1.7]. To assess craniofacial growth, standard lateral
      cephalometric radiographs were obtained at the start of GH treatment, annually
      during 4 years, and at the end of GH treatment or when growth was less than 1
      cm/year. The mean follow-up period was 6.4 years (SD 1.4). Growth changes were
      compared with boys from a semi-longitudinal reference group of 130 healthy
      subjects, 7-21 years of age. t-tests for independent and paired samples and
      multiple regression analysis were applied. Age- and gender-specific standard
      deviation scores for the cephalometric variables were calculated. Repeated
      measures analysis of variance was used to identify significant covariates over
      time, such as low/high GH dose and GHD/ISS and orthodontic treatment. During the
      study period, eight (out of 40) boys were treated with fixed orthodontic
      appliances, three with functional appliances (activators), and three with other
      appliances (plates and lingual arches). During GH treatment period, an overall
      enhancement in growth of the facial skeleton was observed in boys with short
      stature. The changes induced by GH yielded a more prognathic growth pattern, a
      more anterior position of the jaws in relation to the cranial base, and increased
      anterior rotation of the mandible. The mandibular corpus length and anterior face
      height of the GH-treated boys were greater at the end of the study compared with
      the boys in the reference group. No differences in growth response were noted
      either between the GHD and ISS boys or between those treated with either 33 (low
      dose) or 67 (high dose) microg GH/kg body weight/day. The only change that
      remained significantly correlated with orthodontic treatment was the alteration
      in mandibular ramus height, showing a larger change in the boys who had not
      undergone orthodontic therapy. The findings of this study demonstrate that GH
      treatment has a favourable influence on the craniofacial growth pattern of boys
      with short stature without acromegalic features.

PMID- 17513879
TI  - Lack of lymphoid chemokines CCL19 and CCL21 enhances allergic airway inflammation
      in mice.
AB  - Lymphoid chemokines CCL19 and CCL21 are crucial for the recruitment of
      circulating naive T cells into lymph nodes. However, it is not completely known
      how they contribute to the development of allergic diseases. To determine whether
      the lack of CCL19 and CCL21 affects allergic airway inflammation, CCL19- and
      CCL21-deficient [paucity of lymph node T cells (plt/plt)] and wild-type (WT) mice
      were immunized intra-peritoneally and then challenged intra-nasally with chicken
      ovalbumin (OVA). Plt/plt mice developed more severe allergic airway inflammation
      characterized by increased eosinophils and lymphocytes in bronchoalveolar lavage
      (BAL) and profound inflammation in peribronchiolar and perivascular regions than
      did WT mice. CD4+ alpha4 integrin+ and CD4+ beta7 integrin+ T cells were
      significantly increased in the BAL of OVA-immunized and OVA-challenged (OVA/OVA)
      plt/plt mice compared with OVA/OVA WT mice. Moreover, there were higher levels of
      IL-4 and IL-13 mRNAs and lower levels of IL-2 and IFN-gamma mRNAs in inflamed
      lungs of OVA/OVA plt/plt mice compared with OVA/OVA WT mice. Plt/plt mice
      produced higher levels of total and OVA-specific IgE antibody. Thus, our results
      suggest that lack of lymphoid chemokines CCL19 and CCL21 enhances allergic airway
      inflammation by modulating the recruitment of CD4+ T cells into the lung, the
      balance between Th1 and Th2 cytokines and the IgE production.

PMID- 17513880
TI  - Evidence for carbohydrate recognition and homotypic and heterotypic binding by
      the TIM family.
AB  - The T cell Ig domain and mucin domain (TIM) proteins form a conserved family of
      transmembrane cell-surface glycoproteins expressed by a variety of tissues. Each
      TIM protein contains a single V-type Ig domain, a glycosylated mucin-like domain,
      a transmembrane domain and a cytoplasmic domain. TIM proteins recognize a diverse
      array of ligands, including H-ferritin, galectin-9 as well as other TIM family
      members. In this study, we demonstrate that the Ig domains of murine TIM-1, -3
      and -4 display calcium-dependent binding to ligands expressed by murine
      splenocytes and several non-murine cell lines, indicating non-species-specific
      ligand recognition. Further, the intrafamilial interaction of various TIM family
      Ig domains with surface-expressed TIM-1 and TIM-4 requires an intact TIM-1 and
      TIM-4 glycosylated mucin stalk. Importantly, we also uncovered the previously
      unrecognized potential for homotypic TIM interactions in forming ligand-receptor
      pairs. Using a glycan array screen, we identified the novel capacity of the TIM-3
      Ig domain to recognize specific carbohydrate moieties, suggesting a role for
      carbohydrate modification along with protein epitopes in TIM ligand recognition.
      Identification of the carbohydrate-binding capacity of TIM proteins helps explain
      the diversity of ligands recognized by this family and adds to our understanding
      of homotypic and heterotypic interactions between TIM family members.

PMID- 17513881
TI  - Genetic viability and population history of the giant panda, putting an end to
      the "evolutionary dead end"?
AB  - The giant panda (Ailuropoda melanoleuca) is currently threatened by habitat loss,
      fragmentation, and human persecution. Its dietary specialization, habitat
      isolation, and reproductive constraints have led to a perception that this is a
      species at an "evolutionary dead end," destined for deterministic extinction in
      the modern world. Here we examine this perception by a comprehensive
      investigation of its genetic diversity, population structure, and demographic
      history across its geographic range. We present analysis of 655 base pairs of
      mitochondrial (mt) control region (CR) DNA and 10 microsatellite loci for samples
      from its 5 extant mountain populations (Qinling, Minshan, Qionglai, Liangshan,
      and Lesser Xiangling). Surprisingly, extant populations display average to high
      levels of CR and microsatellite diversity compared with other bear species.
      Genetic differentiation among populations was significant in most cases but was
      markedly higher between Qinling and the other mountain ranges, suggesting,
      minimally, that the Qinling population should comprise a separate management unit
      for conservation purposes. Recent demographic inference using microsatellite
      markers demonstrated a clear genetic signature for population decline starting
      several thousands years ago or even further back in the past, and being
      accelerated and enhanced by the expansion of human populations. Importantly,
      these data suggest that the panda is not a species at an evolutionary "dead end,"
      but in common with other large carnivores, has suffered demographically at the
      hands of human pressure. Conservation strategies should therefore focus on the
      restoration and protection of wild habitat and the maintenance of the currently
      substantial regional genetic diversity, through active management of disconnected
      populations.

PMID- 17513882
TI  - Diversification of NRT2 and the origin of its fungal homolog.
AB  - We investigated the origin and diversification of the high-affinity nitrate
      transporter NRT2 in fungi and other eukaryotes using Bayesian and maximum
      parsimony methods. To assess the higher-level relationships and origins of NRT2
      in eukaryotes, we analyzed 200 amino acid sequences from the Nitrate/Nitrite
      Porter (NNP) Family (to which NRT2 belongs), including 55 fungal, 41
      viridiplantae (green plants), 11 heterokonts (stramenopiles), and 87 bacterial
      sequences. To assess evolution of NRT2 within fungi and other eukaryotes, we
      analyzed 116 amino acid sequences of NRT2 from 58 fungi, 40 viridiplantae (green
      plants), 1 rhodophyte, and 5 heterokonts, rooted with 12 bacterial sequences. Our
      results support a single origin of eukaryotic NRT2 from 1 of several clades of
      mostly proteobacterial NNP transporters. The phylogeny of bacterial NNP
      transporters does not directly correspond with bacterial taxonomy, apparently due
      to ancient duplications and/or horizontal gene transfer events. The distribution
      of NRT2 in the eukaryotes is patchy, but the NRT2 phylogeny nonetheless supports
      the monophyly of major groups such as viridiplantae, flowering plants, monocots,
      and eudicots, as well as fungi, ascomycetes, basidiomycetes, and agaric
      mushrooms. At least 1 secondary origin of eukaryotic NRT2 via horizontal transfer
      to the fungi is suggested, possibly from a heterokont donor. Our analyses also
      suggest that there has been a horizontal transfer of nrt2 from a basidiomycete
      fungus to an ascomycete fungus and reveal a duplication of nrt2 in the
      ectomycorrhizal mushroom genus, Hebeloma.

PMID- 17513883
TI  - Evidence for a gram-positive, eubacterial root of the tree of life.
AB  - Directed indels, insertions, and deletions within paralogous genes, have the
      potential to root the tree of life. Here we apply a newly developed rooting
      algorithm, top-down rooting, to indels found in informational and operational
      gene sets, introduce new computational tools for indel analyses, and present
      evidence (P < .01) that the root of the tree of life is not present in its
      traditional location, between the Eubacteria and the Archaebacteria. Using indels
      contained in the dihydroorotate dehydrogenase/uroporphyrinogen decarboxylase gene
      pair and in the ribosomal protein S12/beta prime subunit of the RNA polymerase
      gene pair, we exclude the root from within the clade consisting of the Firmicutes
      plus the Archaebacteria and their most recent common ancestor. These results,
      plus previous directed indel studies excluding the root from the eukaryotes,
      restrict the root to just four possible sites. One potential root is on the
      branch leading to the double-membrane prokaryotes, another is on the branch
      leading to the Actinobacteria, another is within the Actinobacteria, and the
      fourth is on the branch leading to the Firmicutes-Archaea clade. These results
      imply (1) that the cenancestral population was not hyperthermophilic, but
      moderate thermophily cannot be excluded for the root on the branch leading to the
      Firmicutes-Archaea clade, (2) that the cenancestral population was surrounded by
      ester lipids and a peptidoglycan layer, and (3) that parts of the mevalonate
      synthesis pathway were present in the population ancestral to the Bacilli and the
      Archaebacteria, including geranylgeranylglyceryl phosphate synthase, an enzyme
      thought to be partially responsible for the unique sn-1 stereochemistry of the
      archaeal glycerol phosphate backbone.

PMID- 17513884
TI  - The B12/CRP index as a simple prognostic indicator in patients with advanced
      cancer: a confirmatory study.
AB  - BACKGROUND: The vitamin B(12)/C-reactive protein Index (BCI) has been proposed as
      a prognostic indicator in patients with advanced cancer. The purpose of this
      study was to confirm the utility of the BCI in palliative care patients. PATIENTS
      AND METHODS: Patients with advanced cancer provided a blood specimen for
      analysis. Demographic and disease-related variables were recorded. Patients were
      followed up for at least 90 days or until death. RESULTS: Patients (n = 329) were
      divided into three groups according to their BCI score. Patients in group 3 (BCI
      >40,000; median survival 29 days) had a significantly (P < 0.01) worse survival
      than patients in group 2 (BCI 10,001-40,000; median survival 43 days) and
      patients in group 1 (BCI < or =10,000; median survival 71 days). However,
      patients in group 1 did not have a significantly better prognosis than those in
      group 2 (P = 0.091). The point estimates for 90-day mortality for each of the
      three risk groups were different from the figures previously reported during the
      development phase of the BCI (group 1, 58.9% versus 47.2%; group 2, 64.0 versus
      72.5%; group 3, 78.9% versus 90.6%). CONCLUSIONS: An elevated BCI (>40,000)
      predicts poor survival in patients with advanced cancer.

PMID- 17513885
TI  - Glycosaminoglycans in Hydra magnipapillata (Hydrozoa, Cnidaria): demonstration of
      chondroitin in the developing nematocyst, the sting organelle, and structural
      characterization of glycosaminoglycans.
AB  - The hydrozoan is the simplest organism whose movements are governed by the
      neuromuscular system, and its de novo morphogenesis can be easily induced by the
      removal of body parts. These features make the hydrozoan an excellent model for
      studying the regeneration of tissues in vivo, especially in the nervous system.
      Although glycosaminoglycans (GAGs) and proteoglycans (PGs) have been implicated
      in the signaling functions of various growth factors and play critical roles in
      the development of the central nervous system, the isolation and characterization
      of GAGs from hydrozoans have never been reported. Here, we characterized GAGs of
      Hydra magnipapillata. Immunostaining using anti-GAG antibodies showed chondroitin
      or chondroitin sulfate (CS) in the developing nematocyst, which is a sting
      organelle specific to cnidarians. The CS-PGs might furnish an environment for
      assembling nematocyst components, and might themselves be components of
      nematocysts. Therefore, GAGs were isolated from Hydra and their structural
      features were examined. A considerable amount of CS, three orders of magnitude
      less heparan sulfate (HS), but no hyaluronan were found, as in Caenorhabditis
      elegans. Analysis of the disaccharide composition of HS revealed glucosamine 2-N
      sulfation, glucosamine 6-O-sulfation, and uronate 2-O-sulfation. CS contains not
      only nonsulfated and 4-O-sulfated N-acetylgalactosamine (GalNAc) but also 6-O
      sulfated GalNAc. The average molecular size of CS and HS was 110 and 10 kDa,
      respectively. It has also been established here that CS chains are synthesized on
      the core protein through the ubiquitous linkage region tetrasaccharide,
      suggesting that indispensable functions of the linkage region in the synthesis of
      GAGs have been conserved during evolution.

PMID- 17513886
TI  - Pectin induces apoptosis in human prostate cancer cells: correlation of apoptotic
      function with pectin structure.
AB  - Treatment options for androgen-independent prostate cancer cells are limited.
      Therefore, it is critical to identify agents that induce death of both androgen
      responsive and androgen-insensitive cells. Here we demonstrate that a product of
      plant cell walls, pectin, is capable of inducing apoptosis in androgen-responsive
      (LNCaP) and androgen-independent (LNCaP C4-2) human prostate cancer cells.
      Commercially available fractionated pectin powder (FPP) induced apoptosis
      (approximately 40-fold above non-treated cells) in both cell lines as determined
      by the Apoptosense assay and activation of caspase-3 and its substrate, poly(ADP
      ribose) polymerase. Conversely, citrus pectin (CP) and the pH-modified CP,
      PectaSol, had little or no apoptotic activity. Glycosyl residue composition and
      linkage analyses revealed no significant differences among the pectins. Mild base
      treatment to remove ester linkages destroyed FPP's apoptotic activity and yielded
      homogalacturonan (HG) oligosaccharides. The treatment of FPP with
      pectinmethylesterase to remove galacturonosyl carboxymethylesters and/or with
      endopolygalacturonase to cleave nonmethylesterified HG caused no major reduction
      in apoptotic activity, implicating the requirement for a base-sensitive linkage
      other than the carboxymethylester. Heat treatment of CP (HTCP) led to the
      induction of significant levels of apoptosis comparable to FPP, suggesting a
      means for generating apoptotic pectic structures. These results indicate that
      specific structural elements within pectin are responsible for the apoptotic
      activity, and that this structure can be generated, or enriched for, by heat
      treatment of CP. These findings provide the foundation for mechanistic studies of
      pectin apoptotic activity and a basis for the development of pectin-based
      pharmaceuticals, nutraceuticals, or recommended diet changes aimed at combating
      prostate cancer occurrence and progression.

PMID- 17513888
TI  - Molecular clock: an anti-neo-Darwinian legacy.

PMID- 17513889
TI  - Modulation of Ubc4p/Ubc5p-mediated stress responses by the RING-finger-dependent
      ubiquitin-protein ligase Not4p in Saccharomyces cerevisiae.
AB  - The Ccr4-Not complex consists of nine subunits and acts as a regulator of mRNA
      biogenesis in Saccharomyces cerevisiae. The human ortholog of yeast NOT4, CNOT4,
      displays UbcH5B-dependent ubiquitin-protein ligase (E3 ligase) activity in a
      reconstituted in vitro system. However, an in vivo role for this enzymatic
      activity has not been identified. Site-directed mutagenesis of the RING finger of
      yeast Not4p identified residues required for interaction with Ubc4p and Ubc5p,
      the yeast orthologs of UbcH5B. Subsequent in vitro assays with purified Ccr4-Not
      complexes showed Not4p-mediated E3 ligase activity, which was dependent on the
      interaction with Ubc4p. To investigate the in vivo relevance of this activity, we
      performed synthetic genetic array (SGA) analyses using not4Delta and not4L35A
      alleles. This indicates involvement of the RING finger of Not4p in transcription,
      ubiquitylation, and DNA damage responses. In addition, we found a phenotypic
      overlap between deletions of UBC4 and mutants encoding single-amino-acid
      substitutions of the RING finger of Not4p. Together, our results show that Not4p
      functions as an E3 ligase by modulating Ubc4p/Ubc5p-mediated stress responses in
      vivo.

PMID- 17513890
TI  - Essential, overlapping and redundant roles of the Drosophila protein phosphatase
      1 alpha and 1 beta genes.
AB  - Protein serine/threonine phosphatase type 1 (PP1) has been found in all
      eukaryotes examined to date and is involved in the regulation of many cellular
      functions, including glycogen metabolism, muscle contraction, and mitosis. In
      Drosophila, four genes code for the catalytic subunit of PP1 (PP1c), three of
      which belong to the PP1 alpha subtype. PP1 beta 9C (flapwing) encodes the fourth
      PP1c gene and has a specific and nonredundant function as a nonmuscle myosin
      phosphatase. PP1 alpha 87B is the major form and contributes approximately 80% of
      the total PP1 activity. We describe the first mutant alleles of PP1 alpha 96A and
      show that PP1 alpha 96A is not an essential gene, but seems to have a function in
      the regulation of nonmuscle myosin. We show that overexpression of the PP1 alpha
      isozymes does not rescue semilethal PP1 beta 9C mutants, whereas overexpression
      of either PP1 alpha 96A or PP1 beta 9C does rescue a lethal PP1 alpha 87B mutant
      combination, showing that the lethality is due to a quantitative reduction in the
      level of PP1c. Overexpression of PP1 beta 9C does not rescue a PP1 alpha 87B, PP1
      alpha 96A double mutant, suggesting an essential PP1 alpha-specific function in
      Drosophila.

PMID- 17513891
TI  - Modeling inheritance of malignant melanoma with DNA markers in Sinclair swine.
AB  - Cutaneous malignant melanoma in Sinclair swine is a hereditary disease that
      develops in utero or during the first 6 weeks of life. In many cases, the tumors
      regress and piglets survive the disease. Two different sets of gene(s) might be
      involved in the disease: tumor initiator (suppressor) locus or loci and loci
      affecting the aggressiveness of the disease (number and stage of tumors). We
      develop maximum-likelihood methods for interval mapping for both types of loci.
      The experimental design consisted of a boar mated to tumor-bearing sows with
      recording of tumor status and number of tumors in the 6 weeks of life of the
      offspring. The model to search for the tumor initiator locus (with alleles T and
      t) was tested by computer simulation. Estimates of penetrances (Psi(TT) and
      Psi(Tt) for genotypes TT and Tt, respectively) were accurate even for small
      family sizes. Statistical power was >99% for a family size of 70 with Psi(TT) = 1
      and Psi(Tt) = 0. The models to test for number of tumors incorporated genotype
      information for the tumor initiator locus. All models were tested with data from
      a single boar family of 72 piglets over swine chromosomes 6 and 8 (SSC6 and
      SSC8). No tumor evidence for initiator loci was found associated with these
      chromosomes. However, association of a QTL affecting number of tumors at birth
      near microsatellite SW1953 on SSC8 was chromosomewise significant (P<0.0124).

PMID- 17513892
TI  - Transportation noise and cardiovascular risk: updated review and synthesis of
      epidemiological studies indicate that the evidence has increased.
AB  - The review provides an overview of epidemiological studies that were carried out
      in the field of community noise and cardiovascular risk. The studies and their
      characteristics are listed in the tables. Risk estimates derived from the
      individual studies are given for 5 dB(A) categories of the average A-weighted
      sound pressure level during the day. The noise sources considered in the studies
      are road and aircraft noise. The health endpoints are mean blood pressure,
      hypertension and ischaemic heart disease, including myocardial infarction. Study
      subjects are children and adults. The evidence of an association between
      transportation noise and cardiovascular risk has increased since the previous
      review published in Noise and Health in the year 2000.

PMID- 17513893
TI  - Waking levels of salivary biomarkers are altered following sleep in a lab with no
      further increase associated with simulated night-time noise exposure.
AB  - The goals of this study were twofold. First, we assessed if waking salivary
      hormone profiles are altered by nighttime noise exposure in a laboratory
      environment. Second, we evaluated the potential influence that sleeping in the
      lab in itself may have had on salivary biomarkers, by comparing results obtained
      following sleep at home. Twelve adults (7 males, 5 females) between 19-25 yrs
      slept at home and in a sleep laboratory. Subjects provided six saliva samples
      during waking hours on the day prior to sleep in the lab, on both days after
      sleeping in the lab and on the day following the resumption of sleep at home.
      Following one night of adaptation, subjects were exposed throughout the 2nd night
      to simulated backup alarms that consisted of trains of 5 consecutive 500 ms
      duration audible tones. The time between the onset of each tone was 1 s and the
      time between trains (offset to onset) was 15 to 20 s. When compared to home
      conditions, cortisol and melatonin levels were higher following sleep in the
      laboratory 30 minutes after awakening. However, no significant differences were
      noted for any salivary biomarker between the 1st and 2nd night in the sleep lab,
      suggesting that these endpoints were not influenced by exposure to noise on the
      2nd night. Waking profiles of alpha-amylase were not influenced by where the
      subjects slept. Subjective reports of sleep disturbance following sleep in the
      lab were also obtained. For most of the day there was no apparent influence of
      the laboratory noise exposure. However, subjects did report more sleepiness
      during the evening (8 pm) following the 2nd night in the laboratory. In general,
      overall sleep quality was rated slightly higher upon awakening from sleep at
      home. Factors that might have contributed to the observations in this study are
      discussed, including those related to the potentially non-representative sample.

PMID- 17513894
TI  - Hearing loss in young men: possible aetiological factors.
AB  - In the present retrospective register study a very large data base consisting of
      screening audiograms obtained at military conscription of 18-year-old Swedish men
      was used. The study group comprised 450,175 men, aged 18 years, tested at
      conscription to military service. There were nine age groups covering a 24-year
      period, from 1971 to 1995. This database was compared with a number of different
      pre- and postnatal factors with possible influence on the hearing function. This
      ecologic methodology gives tentative clues (but no proof) of possible
      ototraumatic influences. The hearing capacity was fairly similar during the
      entire span of the study and only small variations were observed. There was a
      slight tendency of better hearing capacity in the later age groups, compared with
      the earlier ones. The mean thresholds of the frequencies 4 and 6 kHz were
      slightly elevated in 1971, 1976 and, to some extent also in 1992. We tried to
      calculate the levels of leisure noise exposure during the study period. There was
      no apparent tendency of reduced noise levels, on the contrary the noise levels
      seemed to increase. The treatment programmes for acute otitis media (AOM)
      underwent considerable changes during the period from the early fifties to the
      early eighties, when the participants were pre-school children. One possible
      explanation for the slight improvement of the hearing capacity could be less
      ototraumatic influence of AOM. Data about the occurrence of four common epidemic
      diseases, covering the periods preceding and succeeding the years when the
      participants were born indicated that influenza and possibly pertussis (whooping
      cough), constitute putative prenatal risk factors for mild to moderate high
      frequency hearing loss.

PMID- 17513895
TI  - Audiological findings in workers exposed to styrene alone or in concert with
      noise.
AB  - Audiological testing, interviews and exposure measurements were used to collect
      data on the health effects of styrene exposures in 313 workers from fiberglass
      and metal-product manufacturing plants and a mail terminal. The audiological test
      battery included pure-tone audiometry, distortion product otoacoustic emissions
      (DPOAE), psychoacoustic modulation transfer function, interrupted speech, speech
      recognition in noise and cortical response audiometry (CRA). Workers exposed to
      noise and styrene had significantly poorer pure-tone thresholds in the high
      frequency range (3 to 8 kHz) than the controls, noise-exposed workers and those
      listed in a Swedish age-specific database. Even though abnormalities were noted
      on DPOAE and CRA testing, the interrupted speech and speech recognition in noise
      tests were the more sensitive tests for styrene effects. Further research is
      needed on the underlying mechanisms to understand the effects of styrene and on
      audiological test batteries to detect changes in populations exposed to solvents.

PMID- 17513896
TI  - Clinical Results of Carbon Ion Radiotherapy at NIRS.
AB  - In 1994 a Phase I/II clinical study on carbon ion radiotherapy was begun at NIRS
      using HIMAC, which was then the world's only heavy ion accelerator complex
      dedicated to medical use in a hospital environment. Among several types of ion
      species, we have chosen carbon ions for cancer therapy because they had the most
      optimal properties in terms of possessing, both physically and biologically, the
      most effective dose-localization in the body. The purpose of the clinical study
      was to investigate the efficacy of carbon ion radiotherapy against a variety of
      tumors as well as to develop effective techniques for delivering an efficient
      dose to the tumor. The RBE of carbon ions was estimated to be 2.0 to 3.0 along
      the SOBP for acute skin reactions. As of August 2006, a total of 2,867 patients
      had been entered into Phase I/II or Phase II studies and analyzed for toxicity
      and local tumor response. The results have shown that carbon ion radiotherapy has
      the potential ability to provide a sufficient dose to the tumor with acceptable
      morbidity in the surrounding normal tissues. Tumors that appear to respond
      favorably to carbon ions include locally advanced tumors and those with
      histologically non-squamous cell type of tumors such as adenocarcinoma, adenoid
      cystic carcinoma, malignant melanoma, hepatoma, and bone/soft tissue sarcoma. By
      taking advantage of the biological and physical properties of high-LET radiation,
      the efficacy of treatment regimens with small fractions in short treatment times
      has been confirmed for almost all types of tumors in carbon ion radiotherapy.

PMID- 17513897
TI  - Irradiation System for HIMAC.
AB  - Clinical trials of carbon radiotherapy started at HIMAC in 1994 using three
      treatment rooms and four beam ports, two horizontal and two vertical. The broad
      beam method was adopted to make a three-dimensionally uniform field at an
      isocenter. A spot beam extracted from an accelerator was laterally spread out by
      using a pair of wobbler magnets and a scatterer. A bar ridge filter modulated the
      beam energy to obtain the spread out Bragg peak (SOBP). The SOBP was designed to
      be flat in terms of the biological dose based on the consideration that the field
      consisted of various beams with different LET. Finally, the field of 20 cm in
      diameter with +/- 2.5% uniformity was formed at the isocenter. The width of the
      maximum SOBP was 15 cm. When treating the lung or liver, organs that move due to
      breathing, the beam was irradiated only during the expiration period in a
      respiration-gated irradiation method. This reduced the treatment margin of the
      moving target. In order to prevent normal tissues adjacent to the target volume
      from irradiation by an unwanted dose, a layer-stacking method was developed. In
      this method, thin SOBP layers which have different ranges were piled up step by
      step from the distal end to the entrance of the target volume. At the same time,
      a multi-leaf collimator was used to change the aperture shape to match the shape
      of each layer to the cross-sectional shape of the target. This method has been
      applied to rather large volume cancers including bone and soft-tissue cancers.
      Only a few serious problems in the irradiation systems have been encountered
      since the beginning of the clinical trials. Overall the systems have been working
      stably and reliably.

PMID- 17513898
TI  - European developments in radiotherapy with beams of large radiobiological
      effectiveness.
AB  - This paper reviews the European activities in the field of tumour therapy with
      beams which have a Radio Biological Effectiveness (RBE) larger than 1. Initially
      neutron beams have been used. Then charged pions promised better cure rates so
      that their use was pursued in the framework of the ;Piotron' project at the Paul
      Scherrer Institute (Switzerland). However both approaches did not meet the
      expectations and in the 80s the EULIMA project became the flagship of these
      attempts to improve the effects of the delivery of radiation doses of large RBE
      with respect to photons, electrons and even protons. The EULIMA ion accelerator
      was never built and it took more than ten years to see the approval, in
      Heidelberg and Pavia, of the construction of the HIT and CNAO ;dual' centres for
      carbon ions and protons. In 2008 they will start treating patients. The
      developments that brought to these construction projects are described together
      with the special features of these two facilities. The third European dual centre
      is being built by Siemens Medical Systems in Marburg, Germany, while other
      facilities have been approved but not yet fully financed in Wiener Neustadt
      (Austria), Lyon (France) and Uppsala (Sweden). Finally the collaboration
      activities of the European Network ENLIGHT are presented together with the recent
      involvements of European industries in the construction of turn-key dual centres
      and the development of a new accelerator concept for hadrontherapy, the
      ;cyclinac'.

PMID- 17513899
TI  - New accelerator facility for carbon-ion cancer-therapy.
AB  - The first clinical trial with carbon beams generated from HIMAC was conducted in
      June 1994. The total number of patients treated as of December 2006 was in excess
      of 3,000. In view of the significant growth in the number of protocols, the
      Japanese government gave its approval for carbon-ion therapy at NIRS as an
      advanced medical technology in 2003. The impressive advances of carbon-ion
      therapy using HIMAC have been supported by high-reliability operation and by
      advanced developments of beam-delivery and accelerator technologies. Based on our
      ten years of experience with HIMAC, we recently proposed a new accelerator
      facility for cancer therapy with carbon ions for widespread use in Japan. The key
      technologies of the accelerator and beam-delivery systems for this proposed
      facility have been under development since April 2004, with the main thrust being
      focused on downsizing the facility for cost reduction. Based on the design and
      R&D studies for the proposed facility, its construction was begun at Gunma
      University in April 2006. In addition, our future plans for HIMAC also include
      the design of a new treatment facility. The design work has already been
      initiated, and will lead to the further development of therapy using HIMAC. The
      following descriptions give a summary account of the new accelerator facility for
      cancer therapy with carbon ions and of the new treatment facility at HIMAC.

PMID- 17513900
TI  - Assessing residual motion for gated proton-beam radiotherapy.
AB  - Gated radiation therapy is a promising method for improving the dose conformality
      of treatments to moving targets and reducing the total volume of irradiated
      tissue. Target motion is of particular concern in proton beam radiotherapy, due
      to the finite range of proton dose deposition in tissue. Gating allows one to
      reduce the extent of variation, due to respiration, of the radiological depth to
      target during treatment delivery. However, respiratory surrogates typically used
      for gating do not always accurately reflect the position of the internal target.
      For instance, a phase delay often exists between the internal motion and the
      motion of the surrogate. Another phenomenon, baseline drifting refers to a
      gradual change in the exhale position over time, which generally affects the
      external and internal markers differently. This study examines the influence of
      these two physiological phenomena on gated radiotherapy using an external
      surrogate.

PMID- 17513901
TI  - Integration of Enhanced Optical Tracking Techniques and Imaging in IGRT.
AB  - In external beam radiotherapy, modern technologies for dynamic dose delivery and
      beam conformation provide high selectivity in radiation dose administration to
      the pathological volume. A comparable accuracy level is needed in the 3-D
      localization of tumor and organs at risk (OARs), in order to accomplish the
      planned dose distribution in the reality of each irradiation session. In-room
      imaging techniques for patient setup verification and tumor targeting may benefit
      of the combined daily use of optical tracking technologies, supported by
      techniques for the detection and compensation of organ motion events. Multiple
      solutions to enhance the use of optical tracking for the on-line correction of
      target localization uncertainties are described, with specific emphasis on the
      compensation of setup errors, breathing movements and non-rigid deformations. The
      final goal is the implementation of customized protocols where appropriate
      external landmarks, to be tracked in real-time by means of non-invasive optical
      devices, are selected as a function of inner target localization. The presented
      methodology features high accuracy in patient setup optimization, also providing
      a valuable tool for on-line patient surveillance, taking into account both
      breathing and deformation effects. The methodic application of optical tracking
      is put forward to represent a reliable and low cost procedure for the reduction
      of safety margins, once the patient-specific correlation between external
      landmarks and inner structures has been established. Therefore, the integration
      of optical tracking with in-room imaging devices is proposed as a way to gain
      higher confidence in the framework of Image Guided Radiation Therapy (IGRT)
      treatments.

PMID- 17513902
TI  - Biological intercomparison using gut crypt survivals for proton and carbon-ion
      beams.
AB  - Charged particle therapy depends on biological information for the dose
      prescription. Relative biological effectiveness or RBE for this requirement could
      basically be provided by experimental data. As RBE values of protons and carbon
      ions depend on several factors such as cell/tissue type, biological endpoint,
      dose and fractionation schedule, a single RBE value could not deal with all
      different radiosensitivities. However, any biological model with accurate
      reproducibility is useful for comparing biological effectiveness between
      different facilities. We used mouse gut crypt survivals as endpoint, and compared
      the cell killing efficiency of proton beams at three Japanese facilities. Three
      Linac X-ray machines with 4 and 6 MeV were used as reference beams, and there was
      only a small variation (coefficient of variance < 2%) in biological effectiveness
      among them. The RBE values of protons relative to Linac X-rays ranged from 1.0 to
      1.11 at the middle of a 6-cm SOBP (spread-out Bragg peak) and from 0.96 to 1.01
      at the entrance plateau. The coefficient of variance for protons ranged between
      4.0 and 5.1%. The biological comparison of carbon ions showed fairly good
      agreement in that the difference in biological effectiveness between NIRS/HIMAC
      and GSI/SIS was 1% for three positions within the 6-cm SOBP. The coefficient of
      variance was < 1.7, < 0.6 and < 1.6% for proximal, middle and distal SOBP,
      respectively. We conclude that the inter-institutional variation of biological
      effectiveness is smaller for carbon ions than protons, and that beam-spreading
      methods of carbon ions do not critically influence gut crypt survival.

PMID- 17513903
TI  - Specification of Carbon Ion Dose at the National Institute of Radiological
      Sciences (NIRS).
AB  - The clinical dose distributions of therapeutic carbon beams, currently used at
      NIRS HIMAC, are based on in-vitro Human Salivary Gland (HSG) cell survival
      response and clinical experience from fast neutron radiotherapy. Moderate
      radiosensitivity of HSG cells is expected to be a typical response of tumours to
      carbon beams. At first, the biological dose distribution is designed so as to
      cause a flat biological effect on HSG cells in the spread-out Bragg peak (SOBP)
      region. Then, the entire biological dose distribution is evenly raised in order
      to attain a RBE (relative biological effectiveness) = 3.0 at a depth where dose
      averaged LET (linear energy transfer) is 80 keV/mum. At that point, biological
      experiments have shown that carbon ions can be expected to have a biological
      effect identical to fast neutrons, which showed a clinical RBE of 3.0 for fast
      neutron radiotherapy at NIRS. The resulting clinical dose distribution in this
      approximation is not dependent on dose level, tumour type or fractionation scheme
      and thus reduces the unknown parameters in the analysis of the clinical results.
      The width SOBP and the clinical / physical dose at the center of SOBP specify the
      dose distribution. The clinical results analysed in terms of TCP were found to
      show good agreement with the expected RBE value at higher TCP levels. The TCP
      analysis method was applied for the prospective dose estimation of
      hypofractionation.

PMID- 17513904
TI  - Specifying carbon ion doses for radiotherapy: the heidelberg approach.
AB  - There are currently no guidelines for prescribing and reporting radiation therapy
      (RT) with ion beams. In this paper an overview over some technical aspects and
      their implication on ion RT are reported. This includes a discussion of the
      difference in the treatment planning systems currently used for active and
      passive beam shaping systems, aspects of patient positioning and target
      definition and dose prescription. Special emphasis is put on the questions
      arising from the use of the beam scanning methods in combination with biological
      treatment plan optimization, which is used in the German heavy ion therapy
      facility at GSI and will also be introduced at the hospital based facility in
      Heidelberg. Furthermore, the Heidelberg approach for the clinical dose
      prescription is compared with the methods developed at HIMAC in Chiba, Japan.

PMID- 17513905
TI  - Comparison of the Methods of Specifying Carbon Ion Doses at NIRS and GSI.
AB  - Due to the RBE variations, the carbon-ion doses (in Gy) are no longer sufficient
      to monitor adequately the biological effect of these radiations. Therefore, "RBE
      dose weighting factors" - W(RBE) - allowing for the RBE variations with energy,
      dose and biological system have to be introduced in the treatment plans in order
      to provide the physician with interpretable information. This paper compares the
      methods employed for this purpose at NIRS and GSI, which are specific of the beam
      delivery system of these institutions. NIRS has a "passive" beam delivery system
      where the dose distribution in the SOBP is determined by a Ridge filter. The dose
      distribution - and thus, the shaping of the filter - is chosen according to the
      clinical situation and determined with respect to W(RBE) factors in order to
      yield a biologically iso-effective SOBP. W(RBE )factors in the SOBP are at first
      derived from a RBE/LET function for HSG cells, then normalized to 3 at a LET of
      80 keV/mum. The latter value of 3 corresponds to the clinical RBE of NIRS
      neutrons, which were found to exhibit the same radiobiological properties as 80
      keV/mum carbon-ions. GSI has a "dynamic" beam delivery system ("spot" or "voxel"
      scanning) making it possible to irradiate irregular volumes and to modulate the
      radiation intensity according to the radiosensitivity of different tissues and/or
      different sub-volumes. Due to the "power" and the resulting complexity of the
      system, W(RBE )factors are determined through an integrated calculation code
      allowing iterative interaction of both physical and radiobiological parameters.
      The "Local Effect Model" (LEM) was developed in this view with the aim of
      deriving carbon-ion W(RBE )factors from the parameters determining the response
      to photons. Advantages and weaknesses of the respective methods will be
      discussed.

PMID- 17513906
TI  - From study design and analysis to conclusion: new horizons for epidemiological
      rigor in sport medicine.

PMID- 17513907
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 agree on appropriate definitions and
      methodologies to standardize 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 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 finalized. At this stage, all authors confirmed their agreement
      with the consensus statement. The agreed-on document was presented to and
      approved by the International Rugby Board Council. Agreement was reached on
      definitions for injury, recurrent injury, nonfatal 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- 17513908
TI  - Managing the risk of injury in sport.
AB  - Because the risk of injury in many sports is high, governing bodies and
      individuals involved with these sports have a responsibility to manage the risks
      at acceptable levels. Risk management provides a structured framework within
      which risks can be identified, evaluated, assessed, and controlled through
      appropriate mitigation strategies. Exploring inferences obtained from the
      relationship between risk and the incidence and severity of injury contributes to
      the understanding and control of risks in sport. Studies related to intrinsic and
      extrinsic risk factors should be focused on determining which factors cause an
      athlete's risk level to fall within the high-risk or low-risk regions of the
      population's risk distribution. Risk values can be used to derive risk contours,
      which illustrate the interdependence of incidence and severity on the development
      of effective risk mitigation strategies. The wide variation in the levels of risk
      across different sports is used to demonstrate the impact that athletes'
      perception and acceptance of risk have on their choice of sport. Finally, the use
      of incidence and severity data for predicting the prevalence of injury in a team
      and for the economic evaluation of intervention programmes is discussed.

PMID- 17513909
TI  - For debate: consensus injury definitions in team sports should focus on
      encompassing all injuries.
AB  - OBJECTIVE: The purpose of this paper is to highlight the most effective method of
      collecting injury data by using a definition that encompasses all injuries into
      the data collection system. The definition provides an accurate picture of injury
      incidence and also allows filtering of records so that data can be reported in a
      variety of comparable ways. DATA SOURCES/SYNTHESIS: A qualitative review of
      literature in team sports, plus expert opinion, served as the basis for data
      collection strategies. Articles were retrieved from SportsDiscus and PubMed using
      the terms "sports injury definition" and "injury definition." These terms were
      searched for the period 1966 to November 2006. RESULTS: One of the major results
      (from this paper) that supports the use of an all-encompassing injury definition
      is that 70% to 92% of all injuries sustained fall into the transient category-
      that is, by only recording injuries that result in missed matches, the majority
      of injuries are missed and therefore injury rates are underreported. CONCLUSION:
      An injury definition should be the most encompassing definition that enables a
      true, global picture of injury incidence to be seen in participation in any team
      sport.

PMID- 17513910
TI  - For debate: consensus injury definitions in team sports should focus on missed
      playing time.
AB  - OBJECTIVE: To compare the most commonly used and proposed injury definitions for
      surveillance systems in team sports and attempt to assess their suitability for
      consensus definitions in terms of reliability and functionality. DATA SOURCES:
      The PubMed and SportDiscus databases were searched for papers on team sports that
      discussed consensus definitions or compared various definitions of injury. DATA
      SYNTHESIS: A continuum between the most broad "tissue damage" definition and the
      most narrow "match time loss only" definition was developed. RESULTS: A "match
      time loss only" injury definition can be reliably and accurately applied but only
      captures a small percentage of the total pool of all "tissue damage" injuries.
      There are some inherent biases in using a match time loss only definition (late
      season matches, matches with unequal breaks between games), but these are clearly
      visible. All other definitions improve the volume of data captured but suffer
      serious theoretical and/or practical flaws with respect to accuracy and
      reliability. No study using a broad definition has demonstrated good reliability
      to date (eg, using 2 independent recorders at the same team). CONCLUSION: A
      "match time loss only" injury definition is the most accurate and reliable of
      those commonly used in team sports. Other injury definitions are broader and may
      be more appropriate for individual team and specific injury studies. However, a
      match time loss definition is the most accurate and reliable tool for comparing
      injury rates at different teams and between different seasons within teams.
      Hence, we recommend this as the basis for the injury definition in a consensus
      statement.

PMID- 17513911
TI  - A framework for recording recurrences, reinjuries, and exacerbations in injury
      surveillance.
AB  - A previous injury can increase the risk of sustaining a similar injury by up to
      an order of magnitude. To understand the role of previous injury as a risk
      factor, it is necessary to consider, among other issues, the clinical status of
      the first (index) injury at the time of the subsequent (recurrent) injury:
      currently, the inconsistent use of descriptive terms for recurrent injuries makes
      this extremely difficult. Although recent consensus statements on injury
      definitions based on return-to-play criteria have provided a consistent
      methodology for recording and reporting index and recurrent injuries, these
      statements do not differentiate between the types of recurrent injuries that can
      occur. This paper presents a recording and reporting framework that
      subcategorizes recurrent injuries into reinjuries and exacerbations on the basis
      of whether a player was fully recovered from the preceding index injury, with the
      state of fully recovered determined by medical opinion. A reinjury is a repeat
      episode of a fully recovered index injury and an exacerbation is a worsening in
      the state of a nonrecovered index injury. With this more detailed framework,
      researchers will be able to investigate risk factors for reinjuries and
      exacerbations separately, and they will be able to investigate how well players
      have been rehabilitated before returning to full training and match play.

PMID- 17513912
TI  - The Orchard Sports Injury Classification System (OSICS) version 10.
AB  - Injury classification systems are generally used in sports medicine (1) to
      accurately classify diagnoses for summary studies, permitting easy grouping into
      parent categories for tabulation and (2) to create a database from which cases
      can be extracted for research on specific injuries. Clarity is most important for
      the first purpose, whereas diagnostic detail is particularly important for the
      second. An ideal classification system is versatile and appropriate for all
      sports and all data collection scenarios. The Orchard Sports Injury
      Classification System (OSICS) was developed in 1992 primarily for the first
      purpose, a specific study examining the incidence of injury at the elite level of
      football in Australia. As usage of the OSICS expanded into different sports,
      limitations were noted and therefore many revisions have been made. A recent
      study found the OSICS-8, whilst superior to the International Classification of
      Diseases Australian Modification (ICD-10-AM) in both speed of use and 3-coder
      agreement, still achieved a lower level of agreement than expected. The study
      also revealed weaknesses in the OSICS-8 that needed to be addressed. A recent
      major revision resulted in the development of the new 4-character OSICS-10. This
      revision attempts to improve interuser agreement, partly by including more
      diagnoses encountered in a sports medicine setting. The OSICS-10 should provide
      far greater depth in classifications for the benefit of those looking to maintain
      diagnostic information. It is also structured to easily collapse down into parent
      classifications for those wanting to preserve basic information only. For those
      researchers wanting information collected under broader injury headings,
      particularly those not using fully computerized systems, the simplicity of the
      OSICS-8 system may still suffice.

PMID- 17513913
TI  - The Sport Medicine Diagnostic Coding System.
AB  - The Sport Medicine Diagnostic Coding System (SMDCS) was developed in 1991 in
      response to the need for a classification system that could capture detail
      relevant to sport-related injury. It employs a 6 character structure with 1 pair
      of digits for each of the body region, the structure, and the diagnosis. This
      format permits sorting of data on the basis of any pair of digits to allow
      analysis of the body region, the structure, and the diagnosis type. They can also
      be combined to search for unique diagnoses. These codes have been used in a
      clinical setting since inception and have also been used in studies on sport
      injury surveillance and injury prevention. A number of organizations currently
      use this system in their ongoing surveillance. With the publication of recent
      consensus statements on injury data collection in the sports of football (soccer)
      and rugby, the SMDCS has been updated with new data columns to "cross map" the
      SMDCS to the broader consensus categories. This manuscript is accompanied by a
      downloadable data file to enable other groups to use the SMDCS for their own
      purposes.

PMID- 17513914
TI  - Risk factors and risk statistics for sports injuries.
AB  - BACKGROUND: Risk factors for sports injuries include characteristics and
      behaviors of athletes and characteristics of sports and the environment that are
      associated with some measure of risk of injury. OBJECTIVE: To introduce risk
      statistics to clinicians evaluating studies of sports injuries. METHODS: Plain
      language review of risk statistics and their practical application to sports
      injuries. RESULTS: The various measures of injury incidence are injury risk
      (proportion of athletes injured in a given period of training, playing, or other
      exposure time), injury rate (number of injuries per unit of exposure time), odds
      of injury (probability injury will happen divided by probability injury will not
      happen), injury hazard (instantaneous proportion injured per unit of time or mean
      injury count per unit of time), and mean time or mean number of playing exposures
      to injury. Effects of risk factors are estimated as values of effect statistics
      representing differences or ratios of one or more of these measures between
      groups defined by the risk factor. Values of some ratios and their sampling
      uncertainty (confidence limits) are estimated with specialized procedures: odds
      ratios with logistic regression, rate ratios with Poisson regression, and hazard
      ratios with proportional hazards (Cox) regression. Injury risks and mean time to
      injury in each group can also be estimated and can give a better sense of the
      effect of a risk factor. Risk factors identified in nonexperimental cohort and
      case-control studies are not always causes of injury; data from randomized
      controlled trials provide stronger evidence of causality. CONCLUSION: Expressing
      risk statistics as meaningful numbers should help clinicians make better use of
      sports injury studies.

PMID- 17513915
TI  - Considering cluster analysis in sport medicine and injury prevention research.
AB  - OBJECTIVE: In the field of sport medicine and injury prevention in sport,
      prospective study designs implementing cluster randomization or grouping of
      subjects by cluster (ie, team, clinic, school, community) are becoming
      increasingly common. However, there are very few published studies in the field
      that adequately account for clustering effects in the design and analysis,
      leading to potentially spurious conclusions. This paper will review the
      implications of using a cluster RCT or other intervention or observational design
      grouping individuals by cluster and to highlight the practical implications of
      appropriate analysis considering the effects of clustering. DATA
      SOURCES/SYNTHESIS: Previously published papers have provided a foundation of
      expertise to discuss the often neglected impact of ignoring the effects of
      cluster in the design and analysis of cluster RCT and other study designs that
      group individuals by cluster in sport medicine. RESULTS: The loss of statistical
      efficiency inherent when a study design implements randomization or grouping by
      cluster is reviewed. Specifically, the effect of cluster design on sample size
      considerations and analysis are discussed in the context of data from a recently
      published cluster RCT examining the effectiveness of a balance training
      prevention strategy in youth basketball. CONCLUSIONS: Researchers in sport
      medicine are encouraged and challenged to consider appropriate research design
      and analytical techniques more consistently when study subjects function in the
      context of a cluster in order to avoid spurious results and misleading
      conclusions.

PMID- 17513916
TI  - A dynamic model of etiology in sport injury: the recursive nature of risk and
      causation.
AB  - The purpose of this manuscript is to outline a new model representing a dynamic
      approach that incorporates the consequences of repeated participation in sport,
      both with and without injury. This model builds on the previous work, while
      emphasizing the fact that adaptations occur within the context of sport (both in
      the presence and absence of injury) that alter risk and affect etiology in a
      dynamic, recursive fashion. Regardless of the type of injury, it is often
      preceded by a chain of shifting circumstances that, when they come together,
      constitute sufficient cause to result in an injury. If we are to truly understand
      the etiology of injury and target appropriate prevention strategies, we must look
      beyond the initial set of risk factors that are thought to precede an injury and
      take into consideration how those risk factors may have changed through preceding
      cycles of participation, whether associated with prior injury or not. This model
      considers the implications of repeated exposure, whether such exposure produces
      adaptation, maladaptation, injury or complete/incomplete recovery from injury.
      When feasible, future studies on sport injury prevention should adopt a
      methodology and analysis strategy that takes the cyclic nature of changing risk
      factors into account to create a dynamic, recursive picture of etiology.

PMID- 17513917
TI  - Understanding causal inference: the future direction in sports injury prevention.
AB  - Although physical activity reduces mortality and morbidity, injuries associated
      with activity may increase both short- and long-term musculoskeletal disability.
      On the basis of basic science and injury epidemiology studies, authors have made
      conclusions about cause and effect (causal inferences) and have suggested various
      interventions to decrease the rate of injuries. However, recent advances in
      epidemiology suggest that the regression/stratification approach to adjustment
      for confounding does not provide an appropriate foundation for causal inference;
      therefore, hypotheses based on traditional analyses may be misleading. The
      purpose of this article is to provide an overview of the basic concepts of injury
      epidemiology related to causes, risk factors, and confounding, and to
      conceptually explain the more recent advances that allow for appropriate
      interpretations of cause and effect.

PMID- 17513918
TI  - Injuries in young ice-hockey players.

PMID- 17513921
TI  - Cervical cancer screening in the 21st century: is it time to retire the PAP
      smear?
AB  - Although cytology-based cervical cancer prevention programs have reduced the
      incidence of cervical cancer in many industrialized countries, the limited
      sensitivity of cervical cytology makes these programs difficult and expensive to
      maintain. Therefore, over the next several years it is likely that we will begin
      to switch from cervical cytology-based screening programs to programs based on
      testing for high-risk types of human papillomavirus (HPV). Multiple large, well
      controlled screening trials have clearly demonstrated that HPV testing is
      considerably more sensitive than cytology (either conventional or liquid-based)
      and only slightly less specific when used in women 30 years of age and older.
      Initially, we will use a combination of cervical cytology and HPV testing to
      screen, but as more data from large screening studies become available, it is
      becoming clear that cytology provides little benefit over using HPV testing alone
      to screen. Therefore, in the future it is likely that we will use HPV testing
      alone to screen, and reserve cervical cytology as a way to determine which HPV
      positive women require additional follow-up or colposcopy.

PMID- 17513922
TI  - Management of heavy menstrual bleeding: is hysterectomy the radical mastectomy of
      gynecology?
AB  - Both hysterectomy for heavy menstrual bleeding and radical mastectomy for breast
      cancer are steeped in the history of surgery and have recently been challenged as
      being too radical for the disorder at hand. Radical mastectomy has largely been
      replaced with local removal of the tumor with subsequent radiation and/or
      chemotherapy. Alternatives to hysterectomy include a number of medical
      interventions, most notably intrauterine progestin-releasing systems, and
      endometrial ablation, a procedure that has a relatively high success rate and one
      that is now feasible for many women in an office or procedure room setting.
      However, although radical mastectomy rates have dropped precipitously,
      hysterectomy rates, at least in the United States remain relatively stable.
      Determining the proportion of hysterectomies that are done for heavy menstrual
      bleeding is difficult, largely because of coding issues, so it is difficult to
      measure the impact of new medical and minimally invasive surgical procedures.
      Nevertheless, it seems clear that many women are not exposed to the plethora of
      options to hysterectomy, a fact that may reflect a number of issues that may
      include training, skill, and financial incentives or disincentives. Clearly,
      options to hysterectomy are not a panacea, but if women are empowered to select
      from all of the options available, the rate of hysterectomy for bleeding should
      decrease while maintaining, or even enhancing the patient's satisfaction with
      care.

PMID- 17513923
TI  - Ovarian conservation at the time of hysterectomy for benign disease.
AB  - Approximately 78% of women between the ages of 45 and 64 years have prophylactic
      oophorectomy when hysterectomy is performed for benign disease to prevent the
      development of ovarian cancer. However, after menopause, the ovary continues to
      produce androstenedione and testosterone in significant amounts and these
      androgens are converted in fat, muscle, and skin into estrone. Evidence suggests
      that oophorectomy increases the subsequent risk of coronary heart disease (CHD)
      and osteoporosis and whereas 14,000 women die of ovarian cancer every year nearly
      490,000 women die of heart disease and 48,000 women die within 1 year after hip
      fracture. PubMed and the Cochrane database were used to identify studies that
      examined the incidence of disease and mortality from 5 conditions that seem to be
      related to ovarian hormones: CHD, ovarian cancer, breast cancer, stroke and hip
      fracture, and also data for death from all other causes. The data were applied to
      a Markov decision analytic computer model to calculate risk estimates for
      mortality from these conditions until the age of 80. The model shows for a
      hypothetical cohort of 10,000 women undergoing hysterectomy and who chose
      oophorectomy (vs. ovarian conservation) between the ages of 50 and 54 [without
      estrogen therapy(ET)], that by the time they reach age 80, 47 fewer women will
      have died from ovarian cancer, but 838 more women will have died from CHD and 158
      more will have died from hip fracture. Therefore, the decision to perform
      prophylactic oophorectomy should be approached with great caution for the
      majority of women who are at low risk of developing ovarian cancer.

PMID- 17513924
TI  - Treatment of stress urinary incontinence--midurethral slings: top-down, bottom
      up, "outside-in," or "inside-out".
AB  - Two randomized trials have reported no differences in efficacy between suprapubic
      arc and tension-free vaginal tape at 2 years. There are no long-term studies
      comparing the inside-out and outside-in transobturator (TOT) approach, although
      short-term data show no difference in cure rates or complications. The short-term
      efficacy of TOT midurethral slings is comparable with the retropubic slings;
      however, preliminary evidence suggests that TOT slings may have a lower success
      rate compared with retropubic slings for the treatment of intrinsic sphincter
      deficiency. The risk of bladder injury may be the least with the "inside-out"
      approach, whereas retropubic techniques have a higher risk of cystotomy as
      compared with the TOT approach. Four randomized controlled trials comparing the
      retropubic and TOT approaches show no differences in rate of de novo urgency,
      retention, frequency, nocturia, or incomplete voiding.

PMID- 17513925
TI  - Office management of stress incontinence: current and future role.
AB  - Approximately 11 million women in the United States may be regularly incontinent.
      More than 80% of women decline any treatment and less than 1% undergoes surgical
      management. It is clear that there is a clinically unmet need and a mandate for
      effective, lower cost, noninvasive treatment. These demands will be met by an
      array of new technologies.

PMID- 17513926
TI  - Biologic grafts and synthetic meshes in pelvic reconstructive surgery.
AB  - Despite the lack of evidence, augmenting pelvic organ prolapse surgery with
      biologic graft or synthetic mesh is increasing. The objective of this review is
      to examine the available grafts and meshes and discuss the current data
      addressing the use of these implants in correction of apical, anterior, and
      posterior prolapse. Most of the studies are retrospective with few randomized
      controlled trials. There is level I evidence suggesting that repair of apical
      prolapse with abdominal sacral colpopexy using synthetic mesh results in improved
      outcomes. However, most of the data concerning graft or mesh incorporation in
      anterior or posterior repairs do not support augmentation with prosthesis.

PMID- 17513927
TI  - Chronic pelvic pain: how many surgeries are enough?
AB  - The key to treatment of chronic pelvic pain is to treat it as the complex disease
      it is. Evidence is reviewed showing that identifying one aspect of the disease
      such as endometriosis or adhesions then treating only that component is not
      likely to be successful. Given our understanding of the neuropathology of chronic
      pelvic pain this failure of traditional therapy is to be expected. This evidence
      is reviewed and supports that an integrated treatment approach holds the most
      promise for a successful outcome. The goal of chronic pelvic pain management is
      for the clinician to identify every pain generator and treat each one.

PMID- 17513928
TI  - Innovations in contraception: a review.
AB  - New forms of contraception have been developed to improve the safety and
      tolerability of contraceptive methods without compromising efficacy. The newest
      developments in contraception including low and ultra-low doses of estrogen, less
      androgenic 19 nor-testosterone progestins, and the nonsteroidal progestin
      drospirenone, the Quick Start method to improve compliance of oral
      contraceptives, and the contraceptive transdermal patch, the vaginal estrogen
      progestin ring, the levonorgestrel intrauterine system, and the hysteroscopic
      transcervical sterilization techniques are discussed.

PMID- 17513930
TI  - Comparison of first and second trimester aneuploidy risk assessment.
AB  - Counseling regarding the options for aneuploidy risk assessment is complicated
      and requires thorough counseling with the patient. Second trimester serum risk
      assessment has been the gold standard because of widespread availability, low
      cost, and vast experience with counseling and performance. First trimester risk
      assessment is becoming more widely available and provides increased sensitivity
      for Down syndrome detection with a detection rate of approximately 87% (95%
      confidence interval: 84.0% to 89.4%), at a fixed false-positive rate of 5%. With
      the advent of first trimester techniques, controversy has arisen as there are
      advocates for the different recently available approaches. In this chapter, we
      outline the various options in a manner that will provide practical information
      for physicians offering such testing. Clearly, implementation of first trimester
      risk assessment requires special training and meticulous quality control
      standards for nuchal translucency and laboratory measurements, access to
      chorionic villus sampling, and also appropriate counseling regarding risk
      assessment options.

PMID- 17513931
TI  - Should we treat periodontal disease during gestation to improve pregnancy
      outcomes?
AB  - Until recently many physicians in the United States including obstetrician
      gynecologists have been relatively unconcerned with oral health. During most
      physical examinations, the oral cavity is given only a rudimentary examination.
      With the recognition of the oral-systemic health care link, physicians have been
      keenly interested in the findings from their dental colleagues in periodontal
      medicine which have convincingly linked periodontal disease with such diverse
      systemic health complications as aging, Alzheimer disease, cardiovascular
      disease, diabetes, and also pregnancy complications including low birth weight,
      preterm delivery, preeclampsia, and early pregnancy loss. Intervention trials
      designed to improve oral health during pregnancy have proven to be safe; however,
      the outcomes have been inconsistent. Further studies will be required to
      determine the nature of the association and the optimal timing and efficacy of
      intervention.

PMID- 17513932
TI  - Contemporary use of cervical cerclage.
AB  - Although it was devised over 50 years ago, only recently controlled randomized
      trials have evaluated the efficacy of cervical cerclage. Cerclage was originally
      devised for women with both prior preterm birth (PTB) and cervical changes in the
      current pregnancy. Evidence suggests that transvaginal cerclage probably prevents
      second trimester loss/PTB in women with >or=3 PTB/second trimester loss (history
      indicated cerclage best placed at 12 to 14 wk); and in women with a prior PTB 16
      to 36 weeks and transvaginal ultrasound cervical length<25 mm in the current
      pregnancy (ultrasound-indicated cerclage at 14 to 23 6/7 wk).

PMID- 17513933
TI  - The 20-week scan: beyond biometry and anatomy.
AB  - The "definition" of the 20-week scan should now be significantly expanded.
      Traditionally, the objectives of such an examination were the determination of
      gestational age, the detection of congenital morphologic defects, and the cursory
      evaluation of placental location and amniotic fluid volume. Remarkable progress
      has been made in intervening years. Great technical strides have been
      accomplished in sonographic resolution. Along with proper training of personnel
      improved diagnostic accuracy for anomaly detection can be anticipated. It is
      likely that the more recent applications of ultrasound such as uterine artery
      Doppler velocimetry and cervical status evaluation could equal or eclipse the
      significance and clinical benefits of anomaly detection.

PMID- 17513934
TI  - Is there a role for tocolytic therapy during conservative management of preterm
      premature rupture of the membranes?
AB  - Conservative management of preterm premature rupture of the membranes (pPROM)
      remote from term has been associated with significant pregnancy prolongation and
      has been shown to reduce infant complications when prophylactic antibiotics and
      antenatal corticosteroids are given concurrently. However, the majority of
      conservatively managed women with pPROM will deliver within 1 week and do not
      accrue the benefits of extended pregnancy prolongation. The utility of tocolytic
      therapy after pPROM remains controversial, but 2 recent surveys of clinician
      practice revealed frequent utilization of tocolysis after pPROM, with magnesium
      sulfate being the most commonly used agent. In this manuscript, we review the
      currently available literature regarding the efficacy, risks, and benefits of
      tocolytic therapy during conservative management of preterm PROM remote from
      term.

PMID- 17513935
TI  - Intrauterine growth restriction: how to manage and when to deliver.
AB  - Intrauterine growth restriction secondary to placental insufficiency is a major
      cause of perinatal morbidity and mortality in the United States. Once
      intrauterine growth restriction is identified, obstetrical management is focused
      on assuring safety while the fetus continues to mature within a potentially
      hostile intrauterine environment. In the United States, the approach to
      management and delivery of the premature growth-restricted fetus is often based
      on serial biophysical profile evaluations, whereas in Europe it is usually based
      on the results of cardiotocography. However, there is no single test that seems
      superior to the other available tests for timing the delivery of the growth
      restricted fetus. Therefore, the decision to deliver a fetus, especially at <32
      weeks, remains mostly on the basis of empirical management.

PMID- 17513936
TI  - Elective cesarean delivery: the pelvic perspective.
AB  - Elective cesarean delivery, or cesarean delivery on maternal request, was the
      focus of a recent State-of-the-Science Conference sponsored by the National
      Institutes of Health. On the basis of the information from comprehensive
      literature review and expert speakers, the panelists determined that weak-quality
      evidence supported elective cesarean delivery over planned vaginal delivery for
      urinary incontinence, although the duration of effect is not clear. For other
      maternal outcomes related to pelvic floor function, including pelvic organ
      prolapse, fecal incontinence and other anorectal symptoms, and sexual function,
      weak-quality evidence did not favor either route of delivery.

PMID- 17513937
TI  - Vaginal birth after cesarean delivery: evidence-based practice.
AB  - Given the high national rate of cesarean delivery in current obstetric practice,
      patients considering vaginal birth after cesarean (VBAC) in subsequent
      pregnancies are frequently encountered. A recently growing body of literature on
      VBAC has produced concrete evidence to define the VBAC-associated risks and
      identify factors influencing success. An evidence-based approach can guide
      practitioners and patients through the complex counseling, decision-making, and
      management issues when considering VBAC delivery.

PMID- 17513938
TI  - Trial of vaginal breech delivery: current role.
AB  - Breech presentation occurs at term in approximately 3% to 4% of singleton
      gestations. This presentation is associated with a variety of maternal and fetal
      conditions including preterm labor, abnormal amniotic fluid volume, hydrocephaly,
      anencephaly, mullerian anomalies, abnormal placentation, and multifetal
      gestation. Cesarean delivery has been associated with increased risk of
      subsequent accreta, placenta previa, hemorrhage, and hysterectomy. The Term
      Breech Trial initially suggested that planned vaginal breech delivery is
      associated with increased neonatal morbidity and mortality compared with planned
      cesarean delivery. Long-term follow-up of these vaginally delivered infants
      contradict the initial findings. Current debate surrounds the dilemma of whether
      the untoward complications of cesarean delivery are warranted given uncertain
      minimal increases in neonatal survival and improvement in neurologic outcome with
      planned cesarean.

PMID- 17513939
TI  - Elective induction: When? Ever?
AB  - The frequency of labor induction has increased significantly in recent years.
      Although medically indicated inductions comprise a portion of this increase,
      elective inductions have increased in frequency as well. Given that elective
      inductions, by definition, provide no benefit from a strictly medical standpoint,
      it is particularly important to evaluate whether women who undergo these
      inductions incur greater risks than those who labor spontaneously. This article
      will assess whether elective inductions are associated with changes in pregnancy
      outcomes, and evaluate how these associations are influenced by parity and
      cervical ripeness.

PMID- 17513940
TI  - Prolonged pregnancy: when should we intervene?
AB  - The timely onset of labor and birth is an important determinant of perinatal
      outcome. Prolonged (postterm) pregnancy--defined as delivery at or beyond 42
      weeks' gestation--complicates 10% of all gestations and is associated with
      increased risks to both fetus (stillbirth, macrosomia, birth injury, meconium
      aspiration syndrome) and mother (cesarean delivery, severe perineal injury,
      postpartum hemorrhage). The risk of routine induction of labor (failed induction
      leading to cesarean delivery) in the era of cervical ripening is lower than
      previously reported. For these reasons, the authors favor a policy of routine
      induction of labor for low-risk pregnancies at 41 weeks' gestation.

PMID- 17513942
TI  - Emodin induces growth arrest and death of human vascular smooth muscle cells
      through reactive oxygen species and p53.
AB  - Percutaneous coronary intervention is the main therapy for revascularization of
      occluded coronary arteries. However, a progressive artery restenosis caused by
      abnormal proliferation and migration of vascular smooth muscle cells (VSMC)
      hinders the effective treatment. In this study, we examined the effect of emodin,
      a natural anthraquinoid compound, on cultured VSMC. Lower doses of emodin
      suppressed cell proliferation and induced unscheduled DNA synthesis. Higher doses
      of emodin increased lumpy chromatin condensation and lysosomes in VSMC,
      suggesting the occurrence of apoptosis and autophagy. Emodin increased production
      of reactive oxygen species (ROS), which was abolished by an NADPH oxidase
      inhibitor diphenylene iodonium (DPI). DPI could also decrease the number of
      apoptosis induced by emodin, suggesting the involvement of ROS in emodin-induced
      apoptosis. Emodin upregulated the protein levels of p53 in a dose-dependent
      manner. Laser confocal microscope showed most of emodin scattering in the
      cytoplasms and a little within the nuclei. These findings collectively indicated
      that emodin induces both growth arrest and death of human VSMCs in 2 independent
      manners, implying it as a promising therapy for preventing restenosis.

PMID- 17513943
TI  - Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced
      hypertensive mouse: involvement of tenascin-C induced by aldosterone-mediated
      inflammation.
AB  - Tenascin-C is an extracellular matrix glycoprotein that is supposed to be a
      profibrotic molecule in various fibrogenic processes. To elucidate its
      significance for myocardial fibrosis in the hypertensive heart, we used a mouse
      model with infusion of angiotensin II and examined results by histology,
      immunohistochemistry, in situ hybridization, and quantitative real-time reverse
      transcriptase polymerase chain reaction (RT-PCR). Angiotensin II treatment
      elevated blood pressure and expression of tenascin-C by interstitial fibroblasts
      in perivascular fibrotic lesions, and angiotensin II infusion caused accumulation
      of macrophages. It also upregulated expression of collagen Ialpha2; IIIalpha1;
      and proinflammatory/profibrotic mediators including transforming growth factor
      beta (TGFbeta), platelet-derived growth factor alpha (PDGF-A), PDGF-B, and PDGF
      receptor alpha, but not IL-1beta and PDGF-receptor beta, in the myocardium.
      Treatment with an aldosterone receptor antagonist, eplerenone, significantly
      attenuated angiotensin II-induced fibrosis, expression of tenascin-C, and
      inflammatory changes without affecting the blood pressure level. In vitro,
      neither eplerenone nor aldosterone exerted any influence on tenascin-C expression
      of cardiac fibroblasts, whereas angiotensin II, TGF-beta1, and PDGF significantly
      upregulated expression of tenascin-C. These results suggest that, in the
      angiotensin II-induced hypertensive mouse heart: (1) tenascin-C may be involved
      in the progression of cardiac fibrosis and (2) aldosterone may elicit
      inflammatory reactions in myocardium, which might, in turn, induce tenascin-C
      synthesis of fibroblasts through at least 2 pathways mediated by TGF-beta and
      PDGF-A-B/PDGF-receptor alpha.

PMID- 17513944
TI  - Hydroxypropyl beta-cyclodextrins: a misleading vehicle for the in vitro hERG
      current assay.
AB  - Delayed cardiac repolarization and fatal proarrhythmia have been linked to block
      of the repolarizing current, Ikr or hERG (human ether-a-go-go related gene)
      current. Thus, determining the potency of hERG block is critical in evaluating
      cardiac safety during preclinical development. Hydroxypropyl beta-cyclodextrins
      (HbetaC) are cyclic oligosaccharides used to enhance drug solubility. To evaluate
      the utility of HbetaC to enhance drug solubility in hERG screening assays, we
      studied the effect of HbetaC on hERG current and the sensitivity of the hERG
      assay to 3 structurally different hERG blocking drugs using whole-cell voltage
      clamp technique and HEK-293 cells expressing the hERG channel. HbetaC inhibited
      hERG activation and tail current and accelerated current deactivation in a
      concentration-dependent manner. HbetaC (6%) reduced the apparent potency of block
      by terfenadine (IC50 12000 nM vs 45 nM), cisapride (IC50 281 nM vs 28 nM), and E
      4031 (163 nM vs 26 nM). Reduced potency of block was consistent with loss of
      activity as a result of complexation with HbetaC by terfenadine and cisapride
      (demonstrated in solubility studies) and interactions with HbetaC by E-4031
      (demonstrated in absorbance studies). These results demonstrate that HbetaC is an
      unsuitable agent for enhancing compound solubility in the in vitro hERG current
      assay and may mask drug effects, allowing potentially dangerous drugs to advance
      into clinical development.

PMID- 17513945
TI  - Effect of diuretic therapy on exercise capacity in patients with chronic angina
      and preserved left ventricular function.
AB  - AIM: This study was designed to determine whether therapy with a diuretic has
      antianginal effects in patients with stable angina who are already treated with a
      traditional antianginal regimen. METHODS AND RESULTS: Forty patients with chronic
      stable angina and normal left ventricular function were randomized in a double
      blind, placebo-controlled study. Background antianginal therapy included beta
      blockers (n = 27), calcium channel antagonists (n = 18), and long-acting nitrates
      (n = 24). Of the patients 30% had diabetes and 75% had a history of hypertension.
      Patients were treated with a diuretic (hydrochlorothiazide 25 mg plus amiloride 5
      mg) or placebo for 21 days. All patients underwent a treadmill exercise test
      before randomization and at day 21. The primary end point was the change in
      treadmill walking time until moderate angina. Diuretic therapy was associated
      with an increase in treadmill walking time of 63 +/- 17 seconds versus 19 +/- 9
      seconds in the placebo group (P = 0.026) and reduced ST-segment depression (0.6
      +/- 0.2 mm versus 0.1 +/- 0.2 mm (P = 0.03). There was a 25% increase in walking
      time in 8 patients (40%) treated with diuretic versus 1 patient (5%) in the
      placebo group (P = 0.02). The increases did not depend on changes in blood
      pressure or heart rate. CONCLUSION: Therapy with hydrochlorothiazide plus
      amiloride has potent antianginal effects in patients with stable angina and
      preserved left ventricular function under treatment with standard antianginal
      therapy. Because most of the study patients had a history of hypertension the
      extrapolation of these findings to patients who did not have hypertension
      requires further investigation.

PMID- 17513946
TI  - Effects of KTJ740, a novel antithrombotic agent, on platelet-derived growth
      factor-induced rat aortic smooth muscle cell proliferation and cell cycle
      progression.
AB  - Hyperproliferation of platelet-derived growth factor (PDGF)-BB-induced vascular
      smooth muscle cell (VSMC) is a hallmark of atherosclerosis and related vascular
      disorders. In the previous study, we reported that KTJ740 [2-chloro-3-(4
      (ethylcarboxy)-phenyl)-amino-1,4-naphthoquinone], a newly synthesized vitamin K
      derivative, has potent antithrombotic effects in mice and antiplatelet activity
      in vitro and ex vivo. In the present study, we have tested that KTJ740 could
      inhibit PDGF-BB-stimulated VSMC proliferation. We have examined the potential
      inhibitory effect of this compound on rat aortic smooth muscle cells (RASMCs).
      Our results show that this compound significantly inhibits PDGF-BB-stimulated
      RASMC number and DNA synthesis in a concentration-dependent manner. Furthermore,
      we have examined its effect on cell cycle progression by flow cytometry. KTJ740
      treatment resulted in a significant arrest in cell cycle progression of RASMCs
      induced by PDGF-BB, and this effect was achieved by suppressing activation of
      PDGF-beta receptor (PDGF-Rbeta) tyrosine kinase pathway. These results suggest
      that a possibility of KTJ740 can be a potential agent to control vascular
      disorders and its antiproliferative mechanism may be mediated through PDGF-Rbeta
      tyrosine kinase-dependent signaling pathway.

PMID- 17513947
TI  - Ischemic postconditioning reduces infarct size by activation of A1 receptors and
      K+(ATP) channels in both normal and hypercholesterolemic rabbits.
AB  - The effect of ischemic postconditioning (Postcon) in hypercholesterolemic animals
      is unknown. The objectives were to determine if ischemic preconditioning (IPC)
      and Postcon reduce infarct size in hypercholesterolemic animals and to assess if
      A1 receptors and K+(ATP) channels are involved in Postcon mechanisms. Isolated
      rabbit hearts were perfused according to the Langendorff technique and subjected
      to 30 minutes of ischemia and 30 minutes of reperfusion (G1). In Group 2, IPC was
      performed (1 cycle of 5 minutes ischemia/reperfusion) before 30 minutes of
      ischemia. In Group 3 (G3), Postcon was performed (2 cycles of 30-second
      reperfusion/ischemia) after 30 minutes of ischemia. The G3 protocol was repeated
      in G4 and G5, but during Postcon, an A1 receptor blocker (DPCPX, 200 nM) and
      glybenclamide (K+(ATP), blocker, 0.3 microM) were administered, respectively. The
      G1 to G5 protocols were repeated in animals fed with an enriched cholesterol diet
      (1%) for 4 weeks (G6 to G10). The infarct size was measured by
      triphenyltetrazolium. The infarct size was 16.6 +/- 4.6% in G1 and 25.8 +/- 7.3%
      in G6, and IPC and Postcon reduced the infarct area in both normal and
      hypercholesterolemic animals (G2: 5.1 +/- 1.7% [P < 0.05] and G3: 5.4 +/- 0.9% [P
      < 0.05] in normal animals; G7: 4.1 +/- 1.6% [P < 0.05] and G8 4.8 +/- 0.9% [P <
      0.05], in hypercholesterolemic animals). Both DPCPX and glybenclamide abolished
      the effect reached by Postcon. Thus, Postcon reduces infarct size in normal and
      hypercholesterolemic animals through the activation of A1 and K+(ATP) channels.

PMID- 17513948
TI  - Grape seed proanthocyanidin extracts inhibit vascular cell adhesion molecule
      expression induced by advanced glycation end products through activation of
      peroxisome proliferators-activated receptor gamma.
AB  - Although evidence has shown that grape seed proanthocyanidin extracts (GSPE) can
      selectively inhibit cell adhesion molecule expression induced by advanced
      glycation end products (AGEs), the underlying molecular mechanism has not been
      extensively characterized. To study the antiinflammation mechanism of GSPE, we
      investigated the effect of GSPE on Von Willebrand factor (vWF) content and the
      expression of vascular cell adhesion molecule-1 (VCAM-1) induced by AGEs and the
      effect of GSPE on peroxisome proliferators-activated receptor gamma (PPAR gamma)
      and receptor for AGEs (RAGE) expression in human umbilical vein endothelial cells
      (HUVEC). HUVEC were preincubated with or without GSPE of different concentrations
      (10 mg/L, 50 mg/L, and 100 mg/L) for 4 hours before being treated with 200 mg/L
      AGEs or unmodified bovine serum albumin (BSA) for 24 hours. The expression of
      RAGE and PPAR gamma was investigated by Western blot. VCAM-1 expression was
      measured by flow cytometry and vWF content by enzyme-linked immunosorbent assay
      (ELISA). Results showed that GSPE significantly inhibited the expression of VCAM
      1 in HUVEC and reduced the content of vWF in culture fluid induced by AGEs in a
      dose-dependent manner. AGEs activated the expression of RAGE and inhibited PPAR
      gamma expression in HUVEC, whereas GSPE inhibited the expression of RAGE through
      activation of PPAR gamma in HUVEC simultaneously. These findings indicated that
      GSPE inhibited the cell inflammatory factor expression and protected the function
      of endothelial cell through activation of PPAR gamma expression and inhibition of
      RAGE expression.

PMID- 17513949
TI  - Angiotensin II type 1 receptor expression in polymorphonuclear leukocytes from
      high-risk subjects: changes after treatment with simvastatin.
AB  - Statins may directly interfere with the effects of angiotensin (Ang) II, which is
      a key player in the pathogenesis of atherosclerosis (ATH). Ang II promotes a wide
      array of detrimental processes including a prominent proinflammatory effect,
      increasingly regarded as a target for therapeutic intervention. Because the
      proinflammatory effects of Ang II are exerted mainly through the activation of
      Ang II type 1 receptors (AT1Rs) the present study was devised to investigate by
      means of real-time polymerase chain reaction (PCR) and flow cytometry techniques
      the expression of such receptors on circulating polymorphonuclear leukocytes
      (PMNs) from subjects at high risk for vascular events before and during treatment
      with simvastatin and in sex- and age-matched healthy controls. In vitro
      experiments were also performed to assess the ability of simvastatin to interfere
      with Ang II signaling in human PMNs. In comparison to controls, high-risk
      subjects had similar AT1R expression on the cell membranes but significantly
      higher AT1R messenger ribonucleic acid (mRNA) levels. Treatment of high-risk
      subjects with simvastatin for 30 days resulted in a reduction of AT1R mRNA down
      to the levels of cells from healthy subjects. In vitro, Ang II-induced activation
      of the guanosine triphosphate (GTP)-binding protein Rac 1 in human PMNs was
      inhibited by simvastatin. In conclusion, simvastatin induces downregulation of
      AT1R expression, interferes with Ang II activity in PMNs, and contributes to the
      antiinflammatory profile of statins that can explain the therapeutic effects of
      these drugs.

PMID- 17513950
TI  - Effect of HMGCoA reductase inhibitors on cytochrome P450 expression in
      endothelial cell line.
AB  - Endothelial cells and smooth muscle cells are the major cells that constitute
      blood vessels, and endothelial cells line the lumen of blood vessels. These 2
      types of cells also play an integral role in the regional specialization of
      vascular structure. On the basis of these observations, we designed our study to
      investigate the effect of various statins on CYP expression in endothelial cells.
      3-hydroxymethyl coenzyme A reductase inhibitors play an important role in
      vascular function. The majority of the statins available on the market show
      extensive metabolism by cytochrome P450 (CYP) enzymes. Both cell types are
      involved in the bioconversion of arachidonic acid into vasoactive compounds. The
      aim of this study was to demonstrate the effect of statins on cytochrome P450
      expression in endothelial cells. Our results show that endothelial cells
      expressed both CYPs involved in epoxyeicosatrienoic acids (EETs) and
      hydroxyeicosatetraenoic acids (HETEs) production and the nuclear receptor
      implicated in cytochrome P450 regulation. Treatment of endothelial cells with
      lovastatin increased CYP2C9 expression. After 96 hours of treatment, fluvastatin
      and lovastatin clearly increased CYP2C9 protein level. CAR but not PXR was
      expressed in endothelial cells, indicating that the upregulating effect of
      statins on CYP2C9 in endothelial cells could be mediated through CAR only due to
      the lack of expression of PXR in these cells.

PMID- 17513951
TI  - Platelet aggregometry and receptor binding to predict the magnitude of
      antithrombotic and bleeding time effects of clopidogrel in rabbits.
AB  - Target levels of ex vivo inhibition of platelet aggregation (IPA) induced by
      adenosine diphosphate (ADP) that produce clinically relevant effects of
      clopidogrel, a P2Y12 antagonist, are unclear. We examined standard and modified
      IPA and P2Y12 receptor occupancy as predictors of antithrombotic (% thrombus
      weight reduction) and bleeding time (BT, fold-increase over control) effects of
      clopidogrel in rabbit models of carotid artery thrombosis and cuticle bleeding,
      respectively. Standard and modified IPA with 20 microM ADP were measured in the
      absence and presence of partial P2Y1 blockade, respectively. Clopidogrel
      maximally produced standard IPA of 57% +/- 5%, antithrombotic effect of 85% +/-
      1%, BT increase of 6.0 +/- 0.4-fold and P2Y12 receptor occupancy of 87% +/- 5%.
      Surprisingly, a clopidogrel dose that produced a low standard IPA of 17% +/- 4%
      and P2Y12 receptor occupancy of 39% +/- 5% achieved a significant antithrombotic
      activity of 55% +/- 2% with a moderate increase in BT of 2.0 +/- 0.1-fold. This
      underestimation of clopidogrel efficacy by standard IPA was improved by measuring
      either modified IPA or P2Y12 receptor occupancy. These results suggest that in
      clopidogrel-treated rabbits, low standard IPA is associated with significant
      antithrombotic effects. Moreover, modified IPA and P2Y12 receptor occupancy
      appear to better predict the magnitude of clopidogrel's efficacy compared with
      standard IPA, which may be a better predictor of BT.

PMID- 17513952
TI  - 2-APB induces instability in rat left atrial mechanical activity.
AB  - Atrial contractile abnormalities are common clinical disorders but few
      pharmacological models can reliably produce such abnormalities in isolated atrial
      muscle. Since sarcoplasmic reticulum (SR) calcium leak may underlie these
      contractile irregularities, we investigated whether 2-aminoethoxydiphenyl borate
      (2-APB), a calcium leak-inducer, affects mechanical function in isolated,
      superfused rat left atria. Exposing left atria paced at 3 Hz to >10 microM 2-APB
      produced sporadic mechanical events that occurred in the absence of pacing
      stimulus. Prolonging atrial diastole in the presence of 2-APB produced
      spontaneous mechanical activity (SMA) defined as numerous mechanical events
      occurring in the absence of pacing stimulus. SMA depends on atrial sodium and
      chloride gradients as decreasing superfusate concentration of either ion
      suppressed SMA. Increasing superfusate potassium to produce an EK of
      approximately -74mV reversed SMA, revealing possible membrane potential
      sensitivity. Mechanical function decreased with time in left atria treated with 2
      APB and low sodium or the anion transport inhibitor 4,4'-diisothiocyanatostilbene
      2,2'-disulfonic acid (DIDS) compared with atria exposed to low sodium or DIDS
      alone, suggesting 2-APB may decrease left atrial SR activator calcium. Thus, 2
      APB produces instability in regular left atrial mechanical activity that may
      require forward-mode sodium-calcium exchange and chloride channel activities.
      This data identify a new model for studying atrial contractile abnormalities.

PMID- 17513953
TI  - Orthotic management in adolescent idiopathic scoliosis: leveling the playing
      field.

PMID- 17513954
TI  - A comparison of the thoracolumbosacral orthoses and providence orthosis in the
      treatment of adolescent idiopathic scoliosis: results using the new SRS inclusion
      and assessment criteria for bracing studies.
AB  - This is a retrospective cohort study comparing the effectiveness of the
      thoracolumbosacral orthosis (TLSO) and the Providence orthosis in the treatment
      of adolescent idiopathic scoliosis (AIS) using the new Scoliosis Research Society
      (SRS) Committee on Bracing and Nonoperative Management inclusion and assessment
      criteria for bracing studies. These new criteria will make future studies
      comparable and more valid and accurate. METHODS: We have used a custom TLSO
      (duration, 22 hours/day) and the Providence orthosis (duration, 8-10 hours/night)
      to control progressive AIS curves. Only 83 of 160 patients met the new SRS
      inclusion criteria: age of 10 years and older at initiation of bracing; initial
      curve of 25 to 40 degrees; Risser sign 0 to 2; female; premenarcheal or less than
      1 year past menarche; and no previous treatment. There were 48 patients in the
      TLSO group and 35 in the Providence group. The new SRS assessment criteria of
      effectiveness included the percentage of patients who had 5 degrees or less and 6
      degrees or more of curve progression at maturity, the percentage of patients
      whose curve progressed beyond 45 degrees, the percentage of patients who had
      surgery recommended or undertaken, and a minimum of 2 years of follow-up beyond
      maturity in those patients who were thought to have been successfully treated.
      All patients are evaluated regardless of compliance (intent to treat). RESULTS:
      There were no significant differences in age at brace initiation, initial primary
      curve magnitude, sex, or initial Risser sign between the 2 groups. In the TLSO
      group, only 7 patients (15%) did not progress (<or=5 degrees), whereas 41
      patients (85%) progressed by 6 degrees or more, including the 30 patients whose
      curves exceeded 45 degrees. Thirty-eight patients (79%) required surgery. In the
      Providence group, 11 patients (31%) did not progress, whereas 24 patients (69%)
      progressed by 6 degrees or more, including 15 patients whose curves exceeded 45
      degrees. Twenty-one patients (60%) required surgery. However, when the initial
      curve at initiation of bracing was 25 to 35 degrees, the results improved. Five
      (15%) of 34 patients in the TLSO group and 10 (42%) of 24 patients in the
      Providence group did not progress, whereas 29 patients (85%) and 14 patients
      (58%), respectively, progressed by 6 degrees or more, and 26 patients (76%) and
      11 patients (46%), respectively, required surgery. CONCLUSIONS: Using the new SRS
      bracing criteria, the Providence orthosis was more effective for avoiding surgery
      and preventing curve progression when the primary initial curves at bracing was
      35 degrees or less. However, the overall success of orthotic management for AIS
      in both groups was inferior to previous studies. Our results raise the question
      of the effectiveness of orthotic management in AIS and support the need for a
      multicenter, randomized study using these new criteria.

PMID- 17513955
TI  - Effectiveness of the SpineCor brace based on the new standardized criteria
      proposed by the scoliosis research society for adolescent idiopathic scoliosis.
AB  - The purpose of this prospective observational study was to evaluate the
      effectiveness of the Dynamic SpineCor brace for adolescent idiopathic scoliosis
      in accordance with the standardized criteria proposed by the Scoliosis Research
      Society Committee on Bracing and Nonoperative Management. They proposed these
      guidelines to make the comparison among studies more valid and reliable. From
      1993 to 2006, 493 patients were treated using the SpineCor brace. Two hundred
      forty-nine patients met the criteria for inclusion, and 79 patients were still
      actively being treated. Overall, 170 patients have a definitive outcome. All
      girls were premenarchal or less than 1 year postmenarchal. Assessment of brace
      effectiveness included (1) percentage of patients who have 5 degrees or less
      curve progression, and percentage of patients who have 6 degrees or more
      progression; (2) percentage of patients who have been recommended/undergone
      surgery before skeletal maturity; (3) percentage of patients with curves
      exceeding 45 degrees at maturity (end of treatment); and (4) Two-year follow-up
      beyond maturity to determine the percentage of patients who subsequently
      underwent surgery. Successful treatment (correction, >5 degrees, or
      stabilization, +/-5 degrees) was achieved in 101 (59.4%) of the 170 patients from
      the time of the fitting of the SpineCor brace to the point in which it was
      discontinued. Thirty-nine immature patients (22.9%) required surgical fusion
      while receiving treatment. Two (1.2%) of 170 patients had curves exceeding 45
      degrees at maturity. One mature patient (2.1%) required surgery within 2 years of
      follow-up beyond skeletal maturity. The conclusion drawn from these findings is
      that the SpineCor brace is effective for the treatment of adolescent idiopathic
      scoliosis. Moreover, positive outcomes are maintained after 2 years because 45
      (95.7%) of 47 patients stabilized or corrected their end of bracing Cobb angle up
      to 2 years after bracing. Therapeutic study-investigating the results of
      treatment: level II.

PMID- 17513956
TI  - Safety and efficacy of posterior instrumentation for patients with congenital
      scoliosis and spinal dysraphism.
AB  - OBJECTIVE: Instrumentation and correction of severe congenital scoliosis,
      particularly in patients with spinal dysraphism, has been reported to cause a
      high potential rate of neurological compromise after instrumentation. The aim of
      this study was to evaluate the safety and efficacy of posterior instrumentation
      and correction of congenital scoliosis with accompanying spinal dysraphism. LEVEL
      OF EVIDENCE: Level IV therapeutic studies. METHODS: Retrospective x-ray
      measurements to analyze the efficacy and the evaluation of hospital charts to
      document the intraoperative and postoperative complications were performed for a
      consecutive patient series. Scoliosis Research Society-22 questionnaire was used
      to analyze the health-related quality of life. RESULTS: Twenty-two patients (18
      girls and 4 boys) formed the basis of the study. The average age was 12 years
      (range, 7-18 years) and the average follow-up period was 3.2 years (range, 2-10
      years). The types of spinal dysraphism were diastematomyelia in 20 patients and
      syringomyelia with tethered cord in 2 patients. Twelve patients had previous
      surgery and 3 patients had simultaneous surgeries for spinal dysraphism.
      Posterior instrumentation with/without anterior release and fusion was performed
      in all patients. Major curve was corrected from an average of 71 degrees to 40
      degrees (correction rate, 43.6%). The compensatory curve was corrected from an
      average of 47 degrees to 25 degrees (correction rate, 46.8%). The average loss of
      correction at final follow-up was 2.2 degrees for major curve and 3.5 degrees for
      the compensatory curve. The average scores for the 5 domains of Scoliosis
      Research Society-22 questionnaire were 3.5 for function, 3.9 for pain, 3.5 for
      self-image, 3.6 for mental health, 3.9 for satisfaction, and 3.6 for total.
      Neurological monitoring was conducted by using the wake-up test in all patients.
      The overall complication rate was 31%, including neurological compromise in 2
      patients (9%). CONCLUSIONS: Spinal instrumentation was effective for the control
      of deformity with a relatively higher rate of complications. However, with
      respect to high complication rate, the ideal solution for managing the congenital
      cases is still to prevent the progression of the curve with early intervention by
      using the optimal surgical approach for that particular patient.

PMID- 17513957
TI  - Transpedicular hemiepiphysiodesis and posterior instrumentation as a treatment
      for congenital scoliosis.
AB  - Anterior and posterior hemiepiphysiodesis using a transpedicular approach is an
      effective alternative treatment when compared with the traditional convex
      hemiepiphysiodesis or hemivertebrae excision. No study has reported the results
      of instrumentation with transpedicular hemiepiphysiodesis. Our study was a
      retrospective radiographic evaluation to assess the efficacy of transpedicular
      convex hemiepiphysiodesis with short segment instrumented posterior spinal fusion
      for congenital scoliosis. Ten hemivertebrae in 9 patients were evaluated. The
      average patient age was 10.5 years (range, 2.9-14.5 years). The average follow-up
      was 29.7 months. Cobb angles were recorded for the instrumented segment
      (segmental main curve) and the global or entire curve (total main curve). These
      values were compared preoperatively, postoperatively, and at 2-year follow-up.
      The average total main curve improved in 6 of 10 curves, from 35.0 to 29.6
      degrees (15.4%). The average segmental main curve improved in 8 of 10 curves,
      from 30.0 to 21.5 degrees (28.3%). Seven of 10 curves demonstrated either no
      progression or improvement at the average 2-year follow-up. Two curves in older
      patients (greater than 9 years, 10 months) progressed until a comprehensive
      posterior spinal fusion was required. Multiple surgical techniques have been
      developed to provide treatment for progressive congenital scoliosis.
      Transpedicular hemiepiphysiodesis with a short segment instrumented posterior
      spinal fusion is a safe and effective treatment method to halt the progression of
      congenital scoliosis due to a hemivertebra in patients who are skeletally
      immature.

PMID- 17513958
TI  - Perioperative complications after surgical correction in neuromuscular scoliosis.
AB  - PURPOSE: To evaluate the perioperative complications associated with surgical
      correction in neuromuscular scoliosis and to identify the risk factors associated
      with these complications. METHODS: A retrospective review of the hospital charts
      of patients with neuromuscular scoliosis who underwent surgical correction at a
      medical center was performed. RESULTS: Data was available on a total of 175
      patients. The overall perioperative complication rate was 33.1% (96 complications
      in 58 patients). Complications were subdivided into pulmonary issues (19.4%),
      wound and implant infections (9.7%), cardiovascular complications (4.0%),
      intraoperative neurological changes (4.6%), miscellaneous complications (5.7%),
      and problematic instrumentation (3.4%). No patient had an identifiable permanent
      postoperative change in neurological status. The complication rate in patients
      who underwent single-stage procedures (37.4%) was found lower than that in
      patients who underwent staged procedures (57.1%). There were no deaths during the
      perioperative period. CONCLUSIONS: Patients with neuromuscular scoliosis are at
      high risk of developing perioperative complications after surgical correction of
      their deformity (overall rate, 33.1%).

PMID- 17513959
TI  - Unilateral limb deformity due to fibrous tethers: a report of three cases.
AB  - Fibrous tethers are a rare cause of unilateral limb deformity. A review of the
      literature revealed 9 cases previously described, all located in the distal
      femur. We report 3 additional cases of fibrous tethers, 2 of which were located
      in anatomical areas not previously described. The fibrous tethers were excised in
      all cases, and an osteotomy was performed in 2 of the cases. The clinical,
      radiological, and histopathologic findings are discussed for each case.

PMID- 17513960
TI  - Joint distraction and reconstruction in complex knee contractures.
AB  - We retrospectively reviewed the results of joint distraction and reconstruction
      in complex knee contractures in 6 patients with 9 knees. The circular Ilizarov
      fixator was used in all cases. Extensor mechanism alignment with frame in situ
      was performed in 4 cases and alignment of mechanical axis of the lower limb was
      done in 2. All patients had a mean total arc of movement of 79 degrees before
      operation; however, this was nonfunctional because of the degree of flexion
      contracture. Three of the 6 patients were nonambulant before surgery. After joint
      distraction and reconstruction, mean total arc of movement remained unchanged,
      but this was more functional with improvement in the mobility status. At an
      average follow-up of 53 months, the mean flexion contracture was 100 degrees
      (range, 0-70 degrees), with further flexion possible up to 90 degrees (range, 60
      120 degrees). Four patients had no recurrence. All 6 patients were ambulant with
      or without orthosis. Rebound phenomenon with loss of achieved correction was
      observed in 2 patients. Four patients were quite satisfied with results of
      surgery. Realignment of the extensor mechanism and mechanical axis is an
      important part that needs to be addressed in flexion contractures of the knee.
      Proper preoperative planning and staged procedures reduce the risk of recurrence.
      A treatment protocol is proposed to help in planning and further management.

PMID- 17513961
TI  - The mechanical properties of the ligamentum teres: a pilot study to assess its
      potential for improving stability in children's hip surgery.
AB  - The anatomic and histological characteristics of the ligamentum teres and its
      vascular contributions to the femoral head have been well described. The function
      of the ligamentum teres remains poorly understood. Although excision is the
      current standard in treating complete developmental hip dysplasia, we developed
      an interest in maintaining, shortening, and reattaching the ligament to assure
      early postoperative stability in developmental hip dysplasia. To analyze its
      potential for providing hip joint stability, we investigated the biomechanical
      properties of the ligamentum teres in an in vitro porcine model. Six immature
      porcine hips were dissected, with the proximal femur and acetabular anatomy kept
      intact, isolating the ligamentum teres. Specimens were loaded in tension using
      custom fixation rigs at 0.5 mm/s in line with the fibers. Data for displacement
      and force were collected and sampled at 10 Hz for duration of each test. The
      ligamentum teres failed in a stepwise fashion. The mean ultimate load to failure
      was 882 +/- 168 N. Mean stiffness and failure stress were calculated as 86 +/- 25
      N/mm and 10 +/- 2 MPa, respectively. The biomechanical function of the ligamentum
      teres is not inconsequential. We found the ultimate load of the ligamentum teres
      in the porcine model to be similar to those reported for the human anterior
      cruciate ligament. The strength of the ligamentum teres may confirm its potential
      for providing early stability in childhood hip reconstructions. In the setting of
      dysplasia, the preservation and the transfer of the ligamentum teres to augment
      stability should be considered as an adjunct to open reduction.

PMID- 17513962
TI  - Bilateral slipped capital femoral epiphysis: predictive factors for contralateral
      slip.
AB  - The primary goal in treatment of slipped capital femoral epiphysis (SCFE) is to
      prevent further slip by stabilizing the physis. Debate exists concerning
      prophylactic fixation of the uninvolved hip at presentation. Our goal was to
      determine predictive factors for a contralateral slip after presentation with a
      unilateral SCFE. Ninety patients with SCFE and complete radiographs were followed
      up until the bilateral closure of the proximal femoral physis. Chronological age
      at presentation, sex, and race were recorded. Open or closed triradiate cartilage
      was recorded, and a modified Oxford bone age assessment was performed. Twenty
      patients (22%) had bilateral SCFE at presentation, and 70 patients (78%) were
      unilateral. Of these 70 patients, 16 (23%) later developed a contralateral SCFE.
      Analysis revealed that chronological age was the only significant (P = 0.010)
      predictor for developing a contralateral slip. All girls younger than 10 years
      and all boys younger than 12 years who presented with unilateral SCFE developed a
      contralateral slip. Twenty-five percent of girls younger than 12 years and 37% of
      boys younger than 14 years developed a contralateral slip. No girl older than 13
      years and no boy older than 14 years developed a contralateral slip in our
      series. Surgical complications were infrequent and isolated to the side of the
      initial SCFE. Chronological age is a predictor for a contralateral slip in
      patients presenting with a unilateral SCFE. The authors recommend that all girls
      younger than 10 years and all boys younger than 12 years presenting with
      unilateral SCFE should undergo strong consideration for prophylactic screw
      fixation on the contralateral side. In older age groups, prophylactic treatment
      may be considered on a case-by-case basis.

PMID- 17513963
TI  - Risk factors for school absence after acute orthopaedic injury in new york city.
AB  - The purpose of our study is to identify specific factors that affect a child's
      ability to attend school after an acute orthopaedic injury. One hundred and sixty
      four school-aged patients receiving treatment for an acute orthopaedic injury at
      the Division of Pediatric Orthopaedics were interviewed along with their parents.
      Most participants were Hispanic, which reflects the population of the Washington
      Heights section of Manhattan served by our hospital. Follow-up telephone
      interviews were conducted with those parents whose children were unable to return
      to school. The parents were asked of both the total number of school absences and
      whether the child received home instruction. A survey regarding official school
      attendance policy was mailed to the principals of all the schools attended by the
      children in our study. Forty-seven percent of the children were unable to return
      to school immediately after their injuries. Nearly 70% (n = 51) of the children
      who did not immediately return to school attributed their nonattendance to their
      school's attendance policy. Only half of the absentees received home instruction.
      A multivariate analysis showed that both the type of school (public vs private)
      and the use of crutches were statistically significant risk factors for school
      absence. The median household income also trended toward significance in
      predicting school attendance. The responses to our survey regarding official
      school attendance policy demonstrated considerable variability among the schools.
      This study indicates that pediatric orthopaedic injuries and their treatment
      impact the ability of school-aged patients to attend school. Our study shows that
      children's socioeconomic background influences their ability to attend school
      while injured.

PMID- 17513964
TI  - Orthopaedic injuries in children with nonaccidental trauma: demographics and
      incidence from the 2000 kids' inpatient database.
AB  - The purpose of this study was to examine the demographic and injury
      characteristics of children hospitalized with nonaccidental trauma as a causative
      factor using a large national database. Of the nearly 2.5 million cases in the
      database, 1794 (0.1%) were identified through diagnostic coding of abuse. Both
      sexes were equally represented, and two thirds had Medicaid as their primary
      payer. About one half of the children were younger than 1 year, but all ages were
      represented. The most common orthopaedic injuries were fractures of the femur or
      humerus, and most of those fractures occurred in children younger than 2 years.
      The most common nonorthopaedic injuries were contusions and brain injuries, with
      or without skull fracture, and 62 (3.5%) of the abused children died; almost all
      deaths were associated with brain trauma. Nearly one half of the abused
      hospitalized children between the ages of 3 and 20 years had a concomitant
      psychiatric or neurological condition. These data provide the orthopaedic surgeon
      with additional information to assist in identification of potential cases of
      nonaccidental trauma. In addition to presence of long bone fractures in infants
      and toddlers, older children with concomitant psychiatric or neurological
      conditions presenting with nonaccidental injuries should be assessed for possible
      abuse.

PMID- 17513965
TI  - Fractures of the fifth metatarsal in children and adolescents.
AB  - OBJECTIVE: Fractures of the fifth metatarsal are the most common metatarsal
      fractures in children. Their treatment is based on the adult literature. The
      purpose of our study was to identify the different types of fifth metatarsal
      fractures, to determine the mean time to healing, and to examine whether current
      adult recommendations can be extrapolated to children and adolescents. METHODS: A
      total of 103 patients met the inclusion criteria. The fractures were classified
      according to location. Type I represented an apophyseal injury. Type II
      represented tubercle fractures with intra-articular extension. Type III injuries
      represented Jones fracture. Metatarsal neck and shaft fractures were included
      separately. RESULTS: Apophyseal fractures did well with a short-leg walking cast
      for 3 to 6 weeks. Displaced intraarticular fractures had a significant delay in
      healing versus nondisplaced ones. Jones fractures had delays in healing if not
      treated surgically. Neck and shaft fractures did well with casting. CONCLUSIONS:
      Most fractures of the fifth metatarsal in the pediatric population do well
      clinically after a course of walking cast, unless the fracture is an intra
      articular displaced fracture type or the fracture occurs in the proximal
      diaphyseal area. Fixation of Jones fractures in active adolescents should be
      considered to allow faster return to regular activities and prevent refracture.
      We recommend non-weight bearing casts for all angulated or displaced intra
      articular injuries to avoid delays in healing and angulation. From our series, it
      is evident that most pediatric fifth metatarsal fractures behave as those found
      in adults and can be treated similarly.

PMID- 17513966
TI  - Stainless steel flexible intramedullary fixation of unstable femoral shaft
      fractures in children.
AB  - To assess the role of stainless steel flexible intramedullary fixation in
      unstable pediatric femur fractures, we compared a group of 41 stable (transverse
      or oblique) fractures with a group of 40 unstable (spiral and/or comminuted)
      fractures treated with stainless steel (Ender) nails placed through a single
      lateral insertion. The fractures were followed up until clinical and radiographic
      union was evident with an average follow-up period of 13 months. All fractures
      were healed at an average of 1.4 months. No infections or refractures occurred.
      Although minor radiographic angular deformities and shortening were present in
      both groups, no patient had a clinically detectable angular deformity. Two
      patients with stable fracture patterns had 10 to 20 degrees of asymmetry in foot
      progression angles, and 1 patient with an unstable fracture pattern (Winquist
      grade IV comminution) had a 3-cm limb length difference at final follow-up.
      Stainless steel flexible intramedullary fixation is effective for unstable
      pediatric femur fractures if cortical abutment is present.

PMID- 17513967
TI  - Complications after titanium elastic nailing of pediatric tibial fractures.
AB  - A retrospective review of 60 diaphyseal tibia fractures (31 closed and 29 open
      fractures) treated with flexible intramedullary fixation was conducted. All
      charts and radiographs were reviewed. Children ranged in age from 5.1 to 17
      years. Fifty patients with 51 fractures were followed up until union and
      comprised the study group. The mean follow-up period for these 50 patients was 79
      weeks. Forty-five fractures achieved bony union within 18 weeks (mean, 8 weeks).
      Five patients (11%) had delayed healing (3 had delayed unions that ultimately
      healed with casting or observation, and 2 had nonunions that required secondary
      procedures to achieve union [1 patient underwent a fibular osteotomy, and 1
      underwent exchange nailing with a reamed tibial nail]). These 5 fractures
      ultimately healed, with a mean time to union of 41 weeks. Patients with delayed
      healing tended to be older (mean age, 14.1 years) versus the study population as
      a whole (mean age, 11.7 years). In addition to delayed union, other complications
      were observed in the study population. One patient healed with malunion (13
      degree valgus), requiring corrective osteotomy. One patient with a grade II open
      fracture was diagnosed with osteomyelitis at the fracture site after attaining
      bony union. Two patients developed nail migration through the skin, requiring
      modification or nail removal. The fixation of pediatric diaphyseal tibia
      fractures with titanium elastic nails is effective but has a substantial rate of
      delayed healing, particularly in older patients.

PMID- 17513968
TI  - Pediatric fractures of the carpal scaphoid: a retrospective clinical and
      radiological study.
AB  - A retrospective study was undertaken of 22 carpal scaphoid fracture patients
      younger than 18 years. Of these, 17 patients received conservative treatment, and
      5 received treatment involving screw fixation with or without a bone graft from
      the iliac crest. Clinical outcomes were evaluated using the Cooney score.
      Radiographs were analyzed with respect to the site of the fracture, the course of
      the fracture gap, displacement, and time to union. According to the Cooney score,
      in 94% of patients, good or excellent results were obtained. A total of 94% of
      patients considered their result as good or excellent. All fractures healed.
      Malunion was evident in 1 case.

PMID- 17513969
TI  - Postoperative gait velocity and mean knee flexion in stance of ambulatory
      children with spastic diplegia four years or more after multilevel surgery.
AB  - Factors associated with longer-term outcomes of multilevel orthopaedic surgery in
      ambulatory children with cerebral palsy using a multivariate approach were
      evaluated using a retrospective pretest-posttest design. The population included
      20 ambulatory children with spastic diplegia who had undergone multilevel
      orthopaedic surgery with a minimum of 4-year interval between a preoperative and
      a postoperative gait assessment. Multiple regression analysis was used to
      identify factors associated with postoperative velocity and mean knee flexion in
      stance. Independent variables included in the regression models were velocity,
      mean knee flexion in stance, age at preoperative evaluation, Gross Motor Function
      Classification System level, use of ankle-foot orthoses, leg length, age-adjusted
      body mass index, number of surgical procedures, and range of motion of hip and
      knee. Children who demonstrated faster postoperative gait velocity 4 years or
      more after surgery were younger at the time of initial evaluation, had undergone
      fewer surgical procedures, had faster preoperative gait velocity, used ankle-foot
      orthoses postoperatively, and had increased hip extension range of motion
      postoperatively (R = 0.55). Children who demonstrated greater knee flexion in
      stance 4 years or more after surgery had undergone more surgical procedures,
      greater postoperative popliteal angle, and less knee extension range of motion (R
      = 0.73). This study demonstrates the usefulness of a multivariate approach toward
      understanding and predicting outcomes. The results of this study will provide
      clinicians and researchers more information about those factors associated with
      maintained improvements in the longer term and may be useful for treatment
      planning.

PMID- 17513970
TI  - Pectoralis major release to improve shoulder abduction in children with cerebral
      palsy.
AB  - The aim of our study was to evaluate the surgical results after pectoralis major
      muscle release in children with cerebral palsy and to assess a caregiver's
      satisfaction in patient's care after this procedure.Twenty-one shoulders in 13
      patients were analyzed at least 12 months after surgery. All but 1 patient
      involved in our study had quadriplegic type of cerebral palsy involvement. In 17
      limbs, only pectoralis release was performed; in 4 limbs, latissimus dorsi
      release was added. After clinical examination, a questionnaire was used to
      determine the caregiver's assessment. The passive range of abduction and flexion
      was maintained at an angle greater than 90 degrees in 10 patients. External
      rotation was restricted in 6 patients. All caregivers would recommend this
      surgery to another patient. All but one reported improvement in care of the
      patients after surgery. The indication for this surgical procedure is limited
      only to the selected cerebral palsy cases in which custodial care is impaired by
      shoulder adduction contracture. The 2 main indications for the procedure are the
      limitations in the ability to bathe the axilla and the difficulty in dressing.

PMID- 17513971
TI  - Soft tissue reconstruction for type IV-D duplicated thumb: a new surgical
      technique.
AB  - Type IV-D duplicated thumb has the most complex anomalies and difficulties for
      treatment among polydatyly. Double osteotomy is usually recommended to gain the
      best cosmetic and functional outcome. However, 4 cases of type IV-D duplicated
      thumb were treated only by soft tissue procedure in this study. At operation, a
      conjoined A2 pulley was routinely identified, and the flexor pollicis longus
      (FPL) was found bifurcated distal to the conjoined pulley in every of these
      cases. Instead of double osteotomy, a soft tissue procedure that included
      centralization of FPL and A2 pulley reconstruction was pursued to correct these
      special anomalies. The overall clinical results were evaluated by a modification
      of the Tada scoring system based on the range of motion, joint stability,
      alignment of the remaining thumb, and subjective opinion regarding the
      reconstructed thumb after an average follow-up of 3.3 years (range, 2.5-4.7
      years). According to the scoring system, the results were rated as good in 3
      cases and fair in 1 case. From the results, the A2 pulley reconstruction and FPL
      centralization could prove to be an effective method for the treatment of type IV
      D duplicated thumb and could efficiently avoid the residual angular deformities.
      Therefore, we recommend this soft tissue procedure as an alternative surgical
      technique to the double-osteotomy procedure for treating a type IV-D duplicated
      thumb in a very young child, whose bone is still not mature enough for holding
      the fixing pins.

PMID- 17513972
TI  - Bisphosphonate rescue in distraction osteogenesis: a case series.
AB  - Distraction osteogenesis is a powerful stimulus for new bone (and tissue)
      generation (anabolism). Biomechanical stimulation by distraction of the
      regenerate region results in a high rate of tissue and bone production. However,
      catabolism (bone resorption) can also occur, the process potentially accentuated
      in a stress-shielded environment of an external fixator. Regenerate insufficiency
      can result in regenerate bending or fracture after frame removal. Experimental
      evidence has demonstrated that bisphosphonates may mediate improved local limb
      bone mineral density (BMD) and regenerate strength in animal models. Seven
      patients who had undergone limb lengthening using an Ilizarov device were found
      to have regenerate insufficiency. Poor regenerate quality led to consideration
      for intervention. With informed consent, patients received a therapeutic regime
      of intravenous pamidronate (n = 3) or zoledronic acid (n = 4).The mean age was
      13.8 years (SD, +/-3.6 years), with a minimum follow-up period of 4 months after
      fixator removal. The sites of regenerate insufficiency were the proximal tibia (n
      = 6) and the distal femur (n = 1). The mean time interval in the fixator before
      bisphosphonate treatment was 170 days (range, 124-252 days), with an average
      length increase of 4.8 cm (SD, +/-1.1 cm). At time of intravenous bisphosphonate
      treatment, dual-energy x-ray absorptiometry measurements demonstrated a reduced
      BMD (mean, 62.1%; SD, +/-12.6%) in the bone adjacent to the lengthening site of
      the nonoperated side. Mean healing index was high at 79.6 days/cm (range, 64.4
      108.0 days/cm), reflecting the observed regenerate insufficiency. No significant
      systemic complications were encountered. Six of the patient's fixators were
      removed without requirement for other intervention, demonstrating a rapid and
      sustained improvement in local BMD, increasing to a mean of 85.6% (SD, +/-13.3%)
      of the healthy side. One patient did not respond and subsequently healed after
      percutaneous osteogenic protein 1 (bone morphogenetic protein 7) and bone marrow
      injection. Most failed regenerate cases maintain some underlying anabolic
      activity and can be treated successfully with bisphosphonate therapy, which
      reduces catabolism. Only 1 case required percutaneous administration of an
      anabolic therapy to achieve union. These minimally invasive approaches may lessen
      the need for surgery in a group where significant surgical reintervention could
      otherwise be required.

PMID- 17513973
TI  - Decreased bone mineral density in neurofibromatosis type 1: results from a
      pediatric cohort.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic disorder affecting 1 in 3000
      live births. It is well documented to be associated with bony deformities and
      other orthopaedic problems. Based on our observation that NF1 patients undergoing
      orthopaedic surgery often had osteopenic bone, we performed a study to assess the
      bone mineral density of a cohort of children with NF1 without orthopaedic
      defects.Twenty-three patients were recruited from the neurofibromatosis clinic.
      The bone mineral density of the total body, lumbar spine, and proximal femur was
      measured using dual-energy x-ray absorptiometry. Quantitative ultrasound was used
      to measure broadband ultrasonic attenuation at both heels. The group's mean dual
      energy x-ray absorptiometry sex- and age-matched Z scores were below normal (-0.8
      +/- 1.1, -0.8 +/- 1.2, -0.7 +/- 0.8, -0.6 +/- 1.1, -0.6 +/- 0.9, -0.6 +/- 1.1 for
      the total body, arms, legs, lumbar spine, and right and left femoral neck,
      respectively; all P < 0.01). Although some individuals had normal bone mass, 30%
      had total body Z scores below -1.5. The mean heel broadband ultrasonic
      attenuation Z score was also lower than normal (-0.8 +/- 0.6; P < 0.001).
      Children with NF1 have a general tendency toward osteopenia, suggesting an
      abnormal underlying bone phenotype. This may be relevant when considering
      operative intervention and, if better understood, may partially explain poor bone
      healing associated with NF1.

PMID- 17513974
TI  - The transition to adulthood for children with cerebral palsy: what do we know
      about their health care needs?

PMID- 17513975
TI  - Treatment of pediatric both-bone forearm fractures: a comparison of operative
      techniques.

PMID- 17513977
TI  - Treatment of pediatric both-bone forearm fractures: a comparison of operative
      techniques.

PMID- 17513979
TI  - Dystonia with combined antipsychotic and stimulant treatment.

PMID- 17513980
TI  - Texas Children's Medication Algorithm Project: update from Texas Consensus
      Conference Panel on Medication Treatment of Childhood Major Depressive Disorder.
AB  - OBJECTIVE: To revise and update consensus guidelines for medication treatment
      algorithms for childhood major depressive disorder based on new scientific
      evidence and expert clinical consensus when evidence is lacking. METHOD: A
      consensus conference was held January 13-14, 2005, that included academic
      clinicians and researchers, practicing clinicians, administrators, consumers, and
      families. The focus was to review, update, and incorporate the most current data
      to inform and recommend specific pharmacological approaches and clinical guidance
      for treatment of major depressive disorder in children and adolescents. RESULTS:
      Consensually agreed on medication algorithms for major depression (with and
      without psychosis) and comorbid attention-deficit disorders were updated. These
      revised algorithms also incorporated approaches to address issues of suicidality,
      aggression, and irritability. Stages 1, 2, and 3 of the algorithm consist of
      selective serotonin reuptake inhibitor and norepinephrine serotonin reuptake
      inhibitor medications whose use is supported by controlled, acute clinical trials
      and clinical experience. Recent studies provide support that selective serotonin
      reuptake inhibitors in addition to fluoxetine are still encouraged as first-line
      interventions. The need for additional assessments, precautions, and monitoring
      is emphasized, as well as continuation and maintenance treatment. CONCLUSIONS:
      Evidence and expert clinical consensus support the use of selected
      antidepressants in the treatment of depression in youths. The use of the
      recommended antidepressant medications requires appropriate monitoring of
      suicidality and potential adverse effects and consideration of other evidence
      based treatment alternatives such as cognitive behavioral therapies.

PMID- 17513981
TI  - Weight gain and metabolic effects of mood stabilizers and antipsychotics in
      pediatric bipolar disorder: a systematic review and pooled analysis of short-term
      trials.
AB  - OBJECTIVE: To review weight and metabolic effects of mood-stabilizing treatments
      in pediatric bipolar disorder. METHOD: Systematic PubMed/Medline search of
      studies reporting on change in weight and/or glucose/lipid values with mood
      stabilizing drugs in at least nine pediatric patients with bipolar disorder.
      RESULTS: Nineteen studies, including 24 medication trials in 684 patients (mean
      age, 12.3 +/- 2.9 years) were included. Youngsters received lithium,
      antiepileptics, or their combinations (n = 459), or second-generation
      antipsychotics, alone or combined with lithium or divalproex (n = 225), for 4 to
      48 (mean, 15.4 +/- 12.7) weeks. Weight increase was significant/clinically
      relevant in 18 (75.0%) trials. Weight loss was significant with topiramate (2
      studies, 38 subjects) and present with aripiprazole (1 study, 14 subjects). In
      trials lasting < or =12 weeks, weight gain was greater with second-generation
      antipsychotics plus mood stabilizers (5.5 +/- 1.8 kg) compared to mood-stabilizer
      monotherapy (1.2 +/- 1.9 kg, p <.05, Cohen's d = 2.33) or mood-stabilizer
      cotreatment (2.1 +/- 1.3 kg, p <.05, Cohen's d = 2.17), but not compared to
      antipsychotic monotherapy (3.4 +/- 1.3 kg, p >.05, Cohen's d = 1.34). Nonfasting
      glucose/lipid changes were nonsignificant in two second-generation antipsychotic
      trials (n = 61, 8.9%). CONCLUSIONS: Data are sparse regarding body composition
      effects and lacking for fasting metabolic effects of mood stabilizers in
      pediatric bipolar disorder. Combining antipsychotics with mood stabilizers seems
      to lead to greater weight gain than treatment with one or two mood stabilizers.

PMID- 17513982
TI  - Sex differences in the response of children with ADHD to once-daily formulations
      of methylphenidate.
AB  - OBJECTIVES: Studies of sex differences in methylphenidate response by children
      with attention-deficit/hyperactivity disorder have lacked methodological rigor
      and statistical power. This paper reports an examination of sex differences based
      on further analysis of data from a comparison of two once-daily methylphenidate
      formulations (the COMACS study), which addresses these shortcomings. METHOD:
      Children (184: 48 females; mean [SD] age, 9.58 [1.83] years) entered a double
      blind, crossover trial of Concerta, MetadateCD/Equasym XL, or placebo. Attention
      deficit/hyperactivity disorder symptoms were recorded at seven time points across
      the school day on the seventh day of treatment, using a laboratory classroom
      setting. RESULTS: More females had comorbid anxiety disorder. Males and females
      did not differ with regard to other characteristics. Observed sex differences in
      pharmacodynamic symptom profiles persisted after controlling for placebo and time
      0 hours attention-deficit/hyperactivity disorder scores and the presence of an
      anxiety disorder. Females had a statistically superior response at 1.5 hours post
      dosing and an inferior response at the 12-hour time point relative to their male
      counterparts, no matter which methylphenidate formulation was being assessed.
      CONCLUSIONS: Dose titration of once-daily formulations of methylphenidate should
      ideally be based on systematic evidence of response at different periods across
      the day. The responses of female patients may require additional assessments
      later in the day to determine the optimal dose.

PMID- 17513983
TI  - Behavioral management leads to reduction in aggression in a child and adolescent
      psychiatric inpatient unit.
AB  - OBJECTIVE: Aggression is common in children and adolescents admitted to
      psychiatric inpatient units. Few interventions for reducing aggressive behaviors
      have been identified. This study aimed to evaluate the impact of a milieu-based
      behavioral management program on the frequency of aggressive behaviors in a child
      and adolescent mental health inpatient unit. METHOD: The behavioral management
      program incorporated individualized patient management plans, early detection and
      prevention, staff training, reinforcement of appropriate behaviors, and
      intervention using the least restrictive option. Outcomes were assessed for 6
      months before and after program introduction, and included episodes of aggressive
      behavior, injuries, use of physical restraint, seclusion, p.r.n. sedation, use of
      security services, and staffing factors. RESULTS: Implementation of behavioral
      management led to a significant reduction in the episodes of aggressive behavior
      (p < .05) and other unwanted outcomes including injuries (p < .05), use of
      physical restraint (p < .001), and duration of seclusion (p < .001). These
      outcomes were achieved without reducing the number of admissions, changing the
      types of patients admitted, increasing staff costs, or increasing the use of
      p.r.n. medications. CONCLUSIONS: Aggressive behaviors in child and adolescent
      psychiatric inpatient units can be reduced by implementing a broad-based
      behavioral management program. These findings highlight the importance of
      organizational approaches to behavior and risk management.

PMID- 17513984
TI  - The autism epidemic: fact or artifact?
AB  - OBJECTIVE: We provide an illustration of how changes in methodological factors
      may produce variations in the frequency of autistic disorder (AD) over time and
      project how much of the observed increase in the frequency of AD may be explained
      by methodological factors. METHOD: Using a prediction analysis, we calculate how
      broadening diagnostic criteria, younger age at diagnosis, and improved efficiency
      of case ascertainment could produce temporal trends in the incidence and
      prevalence of AD, measured by calendar year and by year of birth, in a
      hypothetical population of children 0 to 18 across the years 1950 to 2020.
      RESULTS: Time trend studies report an increase as large as 11.0-fold over a 13
      year period for AD. Conservative changes in the three methodological factors
      produced increases in the frequency of AD ranging from 2.1- to 28.8-fold.
      Measures of frequency by year of birth show the largest magnitude of increase;
      predicted prevalence by calendar year and to age 4 by year of birth are
      influenced by changes in the distribution of age at diagnosis, but 1-year
      incidence and prevalence to age 12 are not. DISCUSSION: Methodological factors
      may explain the observed increases in AD over time. To increase confidence in
      reports of time trends, we recommend particular frequency measures and study
      circumstances.

PMID- 17513985
TI  - Interrater reliability of the Anxiety Disorders Interview Schedule for DSM-IV:
      child and parent version.
AB  - OBJECTIVE: The present study determined interrater agreement on diagnoses
      achieved using the parent and child versions of the Anxiety Disorders Interview
      Schedule for Children for DSM-IV (ADIS-C/P) and examined informant, age, and
      gender influences on reliability. METHOD: Diagnoses established for 153 seven- to
      16-year-old children during live administration of the ADIS-C/P were compared to
      diagnoses identified by a second rater after viewing a video recording of the
      interviews. RESULTS: When information from both parent and child interviews was
      used, the level of agreement between raters for principal diagnosis (kappa = .92)
      and the individual anxiety disorders (kappa = .80-1.0) was excellent. Agreement
      on common comorbid disorders was good (kappa = .65-.77). Agreement was also good
      to excellent when diagnoses were assigned based on separate child or parent
      interviews, aside from children's report of externalizing disorders. Age and
      gender did not consistently impact interrater agreement. CONCLUSIONS: The data
      indicate that the present version of the ADIS-C/P provides consistent diagnostic
      results across different clinicians and indicates improvements in the reliability
      of diagnoses following criterion changes in DSM-IV.

PMID- 17513986
TI  - Prenatal exposure to maternal depression and cortisol influences infant
      temperament.
AB  - BACKGROUND: Accumulating evidence indicates that prenatal maternal and fetal
      processes can have a lasting influence on infant and child development. Results
      from animal models indicate that prenatal exposure to maternal stress and stress
      hormones has lasting consequences for development of the offspring. Few
      prospective studies of human pregnancy have examined the consequences of prenatal
      exposure to stress and stress hormones. METHOD: In this study the effects of
      prenatal maternal psychosocial (anxiety, depression, and perceived stress) and
      endocrine (cortisol) indicators of stress on infant temperament were examined in
      a sample of 247 full-term infants. Maternal salivary cortisol and psychological
      state were evaluated at 18-20, 24-26, and 30-32 weeks of gestation and at 2
      months postpartum. Infant temperament was assessed with a measure of negative
      reactivity (the fear subscale of the Infant Temperament Questionnaire) at 2
      months of age. RESULTS: Elevated maternal cortisol at 30-32 weeks of gestation,
      but not earlier in pregnancy, was significantly associated with greater maternal
      report of infant negative reactivity. Prenatal maternal anxiety and depression
      additionally predicted infant temperament. The associations between maternal
      cortisol and maternal depression remained after controlling for postnatal
      maternal psychological state. CONCLUSIONS: These data suggest that prenatal
      exposure to maternal stress has consequences for the development of infant
      temperament.

PMID- 17513987
TI  - Correlates of depressed mothers' sensitivity toward their infants: the role of
      maternal, child, and contextual characteristics.
AB  - OBJECTIVE: To examine various maternal, child, and contextual characteristics, as
      well as the number of risk factors present, to distinguish which factors explain
      variance in the sensitivity of depressed mothers toward their infants. METHOD:
      Participants were depressed mothers (n = 84) with their infants ages 1 month up
      to 1 year. Mothers were videotaped while bathing their children. The recordings
      were rated using the sensitivity scale of the Emotional Availability Scales.
      RESULTS: Three characteristics independently contributed to the explained
      variance in maternal sensitivity: level of education, feelings of parental
      incompetence, and family income. In addition, two subgroups were found to be
      particularly at risk: young mothers with high levels of depressive symptoms and
      low-income mothers who felt insecure about their parental competence. Together,
      these factors explained 23% of the variation in sensitivity in our sample of
      depressed mothers. The number of risk factors explained 9.8% of the variation in
      sensitivity. CONCLUSIONS: The present results have implications for preventive
      interventions. Identifying specific groups at risk for low maternal sensitivity
      at an early stage may lead to favorable outcomes of targeted interventions that
      focus on enhancing depressed mothers' maternal sensitivity and feelings of
      parental competence.

PMID- 17513988
TI  - Social, emotional, and academic competence among children who have had contact
      with child protective services: prevalence and stability estimates.
AB  - OBJECTIVE: To estimate the prevalence and stability of social, emotional, and
      academic competence in a nationally representative sample of children involved
      with child protective services. METHOD: Children were assessed as part of the
      National Survey of Child and Adolescent Well-Being. Children (N = 2,065) ranged
      in age from 8 to 16 years and were assessed at baseline and at 18 and 36 months
      postbaseline. Caregivers, teachers, and youths provided information about
      children's problem behaviors, school achievement, and social competence. Children
      were considered resilient in a domain if they met or exceeded national norms.
      RESULTS: Thirty-seven percent to 49% of children demonstrated resilience in
      mental health, academic, or social domains at any time point. Eleven percent to
      14% of children were resilient across domains at any time point, and only 14% to
      22% of children were consistently resilient within a given domain across all
      three time points. CONCLUSIONS: Resilience, as defined by competence in mental
      health, academic, and social domains, was demonstrated by relatively few
      children. The conditions that promote stable resilience may be difficult to
      achieve among allegedly maltreated children who are likely to face residential
      and caretaker instability. Future research should identify processes that promote
      stability in resilience over time.

PMID- 17513989
TI  - Case series: transformation obsession in young people with obsessive-compulsive
      disorder (OCD).
AB  - This article presents a previously unreported symptom of obsessive-compulsive
      disorder. The young people reported describe a fear of turning into someone or
      something else or taking on unwanted characteristics. We have called this
      transformation obsession. The bizarre nature of this obsession had led to
      misdiagnosis and inappropriate treatments in a number of these patients.
      Recognition of this symptom as an ordinary obsession (unwanted, intrusive,
      repetitive, and associated with an anxiety-reducing compulsion or avoidance)
      facilitates treatment with cognitive-behavioral therapy for obsessive-compulsive
      disorder. Consideration is given to screening for this obsession and whether its
      presence indicates a subtype of obsessive-compulsive disorder.

PMID- 17513990
TI  - Implementing an evidence-based trauma treatment in a state system after September
      11: the CATS project.

PMID- 17513991
TI  - Abnormal sensorimotor integrative function of the larynx in congenital
      laryngomalacia: a new theory of etiology.
AB  - OBJECTIVES/HYPOTHESIS: Laryngomalacia is an enigmatic disease in which laryngeal
      tone is weak, resulting in dynamic prolapse of tissue into the larynx.
      Sensorimotor integrative function of the brainstem and peripheral reflexes are
      responsible for laryngeal tone and airway patency. The goal of this study was to
      elucidate the etiology of decreased laryngeal tone through evaluating the
      sensorimotor integrative function of the larynx. The secondary goal was to
      evaluate factors and medical comorbidities that contribute to the wide spectrum
      of symptoms and outcomes. STUDY DESIGN: Prospective and retrospective collection
      of evaluative data on infants with congenital laryngomalacia at two tertiary care
      pediatric referral centers. METHODS: Two hundred one infants with laryngomalacia
      were divided into three groups on the basis of disease severity (mild, moderate,
      severe). Patients were followed prospectively every 8 to 12 weeks until symptom
      resolution or loss to follow-up. Sensorimotor integrative function of the larynx
      was evaluated in 134 infants by laryngopharyngeal sensory testing (LPST) of the
      laryngeal adductor reflex (LAR) by delivering a duration- (50 ms) and intensity-
      (2.5-10 mm Hg) controlled air pulse to the aryepiglottic fold to induce the LAR.
      Medical records were retrospectively reviewed for medical comorbidities. RESULTS:
      The initial LPST was higher (P < .001) in infants with moderate (6.8 mm Hg) and
      severe disease (7.4 mm Hg) compared with those with mild disease (4.1 mm Hg). At
      1, 3, and 6 months, infants with moderate and severe disease continued to have a
      higher LPST compared with those with mild disease. At 9 months, the LPST
      decreased in all subjects (3.1-3.5 mm Hg, P = .14), which also correlated with
      symptom resolution. Neurologic, genetic, and cardiac diseases were more common in
      infants with severe disease (P < .001). Gastroesophageal reflux disease (GERD)
      and feeding problems more common in those with moderate and severe disease (P <
      .001). Apgar scores were lower in those with severe disease (P < .001). Most
      symptoms resolved within 12 months of presentation. Those with GERD benefited
      from treatment. Supraglottoplasty resulted in few complications. Multiple
      comorbidities (>3) influenced the need for tracheotomy. CONCLUSIONS: Laryngeal
      tone and sensorimotor integrative function of the larynx is altered. The degree
      of alteration correlated with disease severity, indicating that factors that
      alter the peripheral and central reflexes of the LAR have a role in the etiology
      of signs and symptoms of laryngomalacia. GERD, neurologic disease, and low Apgar
      scores influenced disease severity and clinical course, explaining the spectrum
      of disease symptoms and outcomes. Sensorimotor integrative function improved as
      symptoms resolved.

PMID- 17513992
TI  - The resume of your LIFE.

PMID- 17513993
TI  - Delivering quality case management in the home healthcare arena.

PMID- 17513994
TI  - Acuity and case management: a healthy dose of outcomes, part I.
AB  - PURPOSE OF STUDY: This article presents acuity and dosage as two concepts that
      describe how the business case for case management (CM) can be made. Dosage and
      acuity concepts are explained as client need-severity, CM intervention-intensity,
      and CM activity-dose by amount, duration, extent, and timing. Concepts are
      related to the practice of CM using evidence-based knowledge and methods to
      develop instruments that measure and score pivotal CM actions. The purpose of
      this series of three articles is to introduce the two concepts of dosage and
      acuity, discuss their importance for making the business case for CM and for
      translation into evidence-based practice, and present a powerful example of how
      they can be used in everyday CM. The articles feature a specific exemplar, the CM
      Acuity Tools project, and explain how the melding of the acuity and dosage
      innovations will improve the capture of CM outcomes. Part I focuses on the CM
      Acuity Tool(c) instrument. PRIMARY PRACTICE SETTING(S): The article's information
      applies to all CM practice settings, and contains ideas and recommendations
      useful to CM generalists, specialists, supervisors, and outcomes managers. The
      Acuity Tools Project was developed from frontline CM practice in one large,
      national telephonic CM company. METHODOLOGY AND SAMPLE: For dosage, the Huber
      Hall Dosage Model and its testing are described and explained. The intersection
      of dosage and acuity is analyzed. For the Acuity Tools Project, a structured
      literature search and needs assessment launched the development of the suite of
      acuity tools. The resulting gap analysis identified that an instrument to assign
      and measure case acuity specific to CM activities was needed. Clinical experts,
      quality specialists, and business analysts (n = 7) monitored the development and
      testing of the tools, acuity concepts, scores, differentials, and their operating
      principles, and evaluated the validity of the acuity tools' content related to CM
      activities. During the pilot phase of development, interrater reliability testing
      of draft and final tools for evaluator concordance, beta (beta) testing for
      content accuracy and appropriateness, and representative sample size testing were
      done. Expert panel reviews occurred at several junctures along the development
      pathway, including after initial tool draft and both before and after beta-tests
      (n = 5) and pilot tests (n = 28). The pilot testing body (n = 33) consisted of a
      team of case managers (n = 28) along with quality analysts (n = 2), supervisory
      personnel (n = 2), and the lead product analyst (the developer). Product
      evaluation included monitoring weekly reports of open cases for the 28 case
      managers for 3 months (June to August 2000). RESULTS: Positive results generated
      approval from the expert review panel to apply the suite of acuity tools beyond
      (1) the initial draft phase, (2) the test population phase, and then (3) at a
      national CM organization level. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: This
      article defines and discusses acuity and dosage as two practical conceptual tools
      that successfully unite clinical quality and business practices and measure and
      analyze CM activities. The CM Acuity Tool(c) is a master conceptual framework in
      three dimensions that synthesizes key components of CM practice, organized into
      indicators, drivers, and subdrivers. To show value, case managers need to access
      the evidence base for practice, use tools to capture quantities of intervention
      intensity, and specify the activities that produce better outcomes.

PMID- 17513996
TI  - An evidence-based approach to case management model selection for an acute care
      facility: is there really a preferred model?
AB  - PURPOSE OF STUDY: This research seeks to determine whether there is adequate
      evidence-based justification for selection of one acute care case management
      model over another. PRIMARY PRACTICE SETTING(S): Acute Inpatient Hospital.
      METHODOLOGY AND SAMPLE: This article presents a systematic review of published
      case management literature, resulting in classification specific to terms of
      level of evidence. CONCLUSION: This review examines the best available evidence
      in an effort to select an acute care case management model. Although no single
      case management model can be identified as preferred, it is clear that adequate
      evidence-based literature exists to acknowledge key factors driving the acute
      care model and to form a foundation for the efficacy of hospital case management
      practice. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Although no single case
      management model can be identified as preferred, this systematic review
      demonstrates that adequate evidence-based literature exists to acknowledge key
      factors driving the acute care model and forming a foundation for the efficacy of
      hospital case management practice. Distinctive aspects of case management
      frameworks can be used to guide the development of an acute care case management
      model. The study illustrates: * The effectiveness of case management when there
      is direct patient contact by the case manager regardless of disease condition:
      not only does the quality of care increase but also length of stay (LOS)
      decreases, care is defragmented, and both patient and physician satisfaction can
      increase. * The preferred case management models result in measurable outcomes
      that can directly relate to, and demonstrate alignment with, organizational
      strategy. * Acute care management programs reduce cost and LOS, and improve
      outcomes. * An integrated case management program that includes social workers,
      as well as nursing, is the most effective acute care management model. * The
      successful case management model will recognize physicians, as well as patients,
      as valued customers with whom partnership can positively affect financial
      outcomes in terms of reduction in LOS, improvement in quality, and delivery of
      care.

PMID- 17513998
TI  - Ethical dilemmas among nurses as they transition to hospital case management:
      implications for organizational ethics, part I.
AB  - PURPOSE OF THE STUDY: To describe the experiences of ethical concerns by clinical
      nurses as they transitioned into their new role in hospital case management.
      Through this study, an attempt was made to explore experiences of ethical
      concerns and identify the implications for organizational ethics. PRIMARY
      PRACTICE SETTING(S): In this study, nurse case managers practicing in the acute
      hospital setting, military, not-for-profit community, and teaching hospitals were
      interviewed. The majority of the nurse case manager participants were engaged in
      hospital discharge planning and utilization review activities. METHODOLOGY AND
      SAMPLE: An interpretive phenomenological approach was used to identify the themes
      inherent in ethical concerns and articulate them within the context of hospital
      nurse case management. Fifteen participants were interviewed to obtain a
      qualitative description of the nurse case managers' lived experiences of ethical
      dilemmas and how they were resolved. RESULTS: Nurse case managers' perceptions of
      solutions/options to resolve such ethical dilemmas were explored. As nurses
      transition into the expanded role of case management in the present healthcare
      delivery system, they frequently face situations demanding ethical choices and
      judgments to accommodate diverse patient interests and needs. These ethical
      decisions required in daily practice in case management represent ethical
      dilemmas to nurses. The insights derived from the analysis of the interviews have
      implications for nursing practice, education, policy, ethics, and research;
      recommendations for organizations employing nurse case managers in terms of
      recruitment, orientation, training, and continued need for educational support
      are identified. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: 1. The clinical
      decisions required in daily practice of case management represented challenges to
      the nurses. This highlights the critical role of adequate educational orientation
      to case management for beginning case managers. 2. Nurse case managers should be
      cognizant of the "disconnect" that could occur between their obligations to the
      organizations that employ them and the healthcare needs of the patients that they
      advocate for. 3. Aside from the importance of linking patient care outcomes with
      accountability, nurse case managers may need to advocate for policy change and
      system reform.

PMID- 17513999
TI  - Direct access--the best kept secret: a "seasoned" case manager learns from
      personal experience.

PMID- 17514000
TI  - Crucial conversations for healthcare: speak up and help others do the same, part
      III.

PMID- 17514001
TI  - Information systems and case management practice series: introduction to
      information systems and case management information system, part I (of III).

PMID- 17514002
TI  - Ethical realism revisited.

PMID- 17514004
TI  - Nonoccupational medical factors impacting workers' compensation.

PMID- 17514005
TI  - Case management--a bridge for the revenue cycle management team.

PMID- 17514007
TI  - Does local recurrence impact survival in low-grade chondrosarcoma of the long
      bones?
AB  - We hypothesized local recurrence of Grade 1 chondrosarcoma in the long bones of
      the extremity negatively influences survival. To explore that notion, we
      retrospectively reviewed 164 patients treated surgically for Grade 1
      chondrosarcoma of the long bones. Local recurrence occurred in 21 (13%) patients.
      Four patients had progression of tumor grade on recurrence, and six patients had
      more than one local recurrence. Seven of the 21 patients with local recurrences
      had metastasis. Six of the 21 patients with local recurrences died secondary to
      chondrosarcoma. Local recurrence, progression of grade at recurrence, and distant
      metastases all were associated with a decrease in overall survival. The
      difference in survival was not apparent until after 5 years and was more
      pronounced after 10 years. Recurrence may be regarded as a declaration of an
      aggressive phenotype and should be treated as such.

PMID- 17514008
TI  - PMMA is superior to hydroxyapatite for colony reduction in induced osteomyelitis.
AB  - Staphylococcus aureus infection is a serious complication in patients receiving
      orthopaedic implants. Treatment with antibiotic-loaded cements can deliver high
      local concentrations and reduce toxic side effects associated with systemic
      antibiotic administration, but polymethylmethacrylate cement is nondegradable and
      may necessitate additional surgery for removal. Previous studies provide support
      for hydroxyapatite as a biodegradable carrier, but consensus has not been
      achieved. We hypothesized vancomycin-loaded hydroxyapatite was superior to
      vancomycin-loaded polymethylmethacrylate in reducing the number of bacterial
      colony-forming units in the setting of osteomyelitis. Osteomyelitis was induced
      in rats using an established model. Animals then were randomly assigned to a
      control group (no antibiotics), a group treated with vancomycin-loaded
      polymethylmethacry-late, and two groups treated with hydroxyapatite loaded with
      either low-dose or high-dose vancomycin. After 6 weeks we compared the number of
      colony-forming units per gram of harvested bone between groups. Vancomycin-loaded
      hydroxyapatite was inferior to vancomycin-loaded polymethylmethacrylate in
      reducing the number of bacterial colony-forming units and vancomycin-loaded
      polymethylmethacry-late was superior to the control group. We observed no
      difference between low- and high-dose vancomycin-loaded hydroxyapatite groups.
      The poor handling properties of hydroxyapatite paste may explain these findings.
      Based on these results, a hydroxyapatite carrier cannot be recommended for the
      treatment of osteomyelitis.

PMID- 17514009
TI  - Knee disarticulation and hip release for severe lower extremity contractures.
AB  - Severe lower extremity contractures cause many problems for patients and their
      caregivers. Hygiene, skin and perineal care, positioning, and dressing are
      severely compromised. Surgical management of such deformities is challenging and
      results have not been published. We treated eight nonambulatory adults with
      severe and rigid lower extremity contractures with hip release and knee
      disarticulation of 14 extremities. The patients had neurologic disorders with
      spasticity. The indications for surgery were fixed contractures of at least 90
      degrees at the knee and hip that interfered with passive function and quality of
      life. All patients were bed-bound secondary to their contractures. The average
      age at surgery was 57 years; the minimum followup was 6 months (mean, 34 months;
      range, 6-102 months). The average preoperative flexion contractures were 106
      degrees at the hips and 139 degrees at the knees. The average postoperative hip
      flexion contracture was 6 degrees , and there were no serious complications or
      recurrent contractures. Positioning and hygiene problems were universally
      improved, enabling all of the patients to become wheel-chair users, and all
      patients or their caretakers reported resolution of pain.

PMID- 17514010
TI  - Genetic association study of growth hormone receptor and idiopathic scoliosis.
AB  - Although the etiology of scoliosis is multifactorial, genetic factors play an
      important role. Recent linkage studies on familial idiopathic scoliosis revealed
      multiple putative predisposition loci. A genetic association study is
      complementary to linkage studies in defining the genetic basis of complex traits
      of diseases like idiopathic scoliosis. The onset and progression of adolescent
      idiopathic scoliosis is a manifestation of aberrant growth in the spine.
      Meanwhile, a high proportion of patients with adolescent idiopathic scoliosis
      have additional phenotypes, which suggest systemic growth dys-regulation during
      puberty. The growth hormone-insulin-like growth factor axis plays the principle
      role in skeletal growth regulation. Because growth hormone receptor alleles were
      associated with body stature and response to growth hormone treatment, we
      hypothesized the growth hormone receptor is a candidate predisposing and disease
      modifier gene for adolescent idiopathic scoliosis. Five hundred ten girls with
      adolescent idiopathic scoliosis and 363 normal subjects were recruited. Curve
      severity, arm span, and bone mineral densities were recorded. Five polymorphisms
      were studied by polymerase chain reaction-restriction fragment length
      polymorphism. All the genotype and allele frequencies were comparable between
      groups. The Cobb angles among patients of different genotypes were similar. The
      growth hormone receptor did not appear to be a predisposing gene or disease
      modifier gene of adolescent idiopathic scoliosis.

PMID- 17514011
TI  - Linezolid in the treatment of implant-related chronic osteomyelitis.
AB  - New antibiotics have been developed targeting resistant microorganisms; however,
      limited information is available on their use in implant-related chronic
      osteomyelitis. We evaluated the infection control rate of linezolid in treating
      these challenging infections and delineate indications for its use. We
      retrospectively reviewed 22 consecutive adult patients with chronic implant
      related osteomyelitis, treated with linezolid in addition to surgical debridement
      and implant removal. Osteomyelitis was associated with fracture fixation implants
      (n = 18) or arthroplasty implants (n = 4). Methicillin-resistant Staphylococcus
      aureus (MRSA) was the most common pathogen (10 of 22 patients). Fourteen patients
      had one or more comorbidity, including intravenous drug abuse in four patients.
      Indications for linezolid use included preference for oral administration in 13
      patients, presence of vancomycin-resistant enterococcus (VRE) in five patients,
      and development of allergic reactions to vancomycin in four patients. Fourteen
      patients were followed for a minimum of 6 months (mean, 22 months; range, 6-34
      months) with no recurrence of infection. Linezolid is a reasonable alternative
      for treating chronic implant-related osteomyelitis. Our treatment protocol,
      including linezolid, achieved control of infection in all patients despite the
      challenging nature of these infections due to patient comorbidities and resistant
      organisms.

PMID- 17514012
TI  - Novel technique for medullary canal debridement in tibia and femur osteomyelitis.
AB  - Intramedullary infection is a challenging problem and treatment usually includes
      removal of infected hardware and reaming of the medullary canal. We describe a
      new technique for canal debridement and evaluate its infection control rate in
      treating osteomyelitis of the tibia and femur. We retrospectively reviewed 11
      patients with posttraumatic osteomyelitis of the tibia (n = 8) or femur (n = 3).
      Surgery included debridement, implant removal, and reaming of the medullary canal
      with a new device that allows reaming under simultaneous irrigation and
      aspiration. At a minimum followup time of 6 months (mean, 13 months; range, 6-23
      months), we observed no recurrence of infection. Complications included one
      partial loss of a flap, one refracture of a tibia after an automobile versus
      pedestrian accident, and external fixator pin tract infections in one patient.
      These preliminary data suggest the new reaming device may be a useful adjunct for
      debriding intramedullary infections of the tibia and femur.

PMID- 17514013
TI  - HIV and metabolic syndrome: a comparison with the general population.
AB  - OBJECTIVE: To compare the prevalence of metabolic syndrome (MS) in HIV-positive
      patients with that from a sample of a general Italian population. DESIGN: Cross
      sectional study. METHODS: A total of 1263 HIV-infected patients 18 years of age
      or older were recruited in 18 centers for infectious diseases in northern and
      central Italy. Controls were 2051 subjects aged 25 to 74 years representative of
      the residents of Monza, a town in Milan province, who were enrolled in the
      Pressioni Arteriose Monitorate E Loro Associazioni study. RESULTS: The prevalence
      of MS in the HIV group was 20.8%, whereas in the control group, it was only
      15.8%, with the difference being statistically significant. The age- and gender
      adjusted risk of having MS in HIV-infected patients was twice as great as that in
      controls. Compared with controls, HIV-infected patients had a greater prevalence
      of the impaired fasting glucose, increased plasma triglycerides, and reduced high
      density lipoprotein cholesterol components. MS prevalence was similar in treated
      and never-treated HIV-infected patients, and so were the various MS components.
      CONCLUSIONS: The risk of MS is greater in HIV-infected patients compared with the
      general population because of a greater prevalence of lipid and glucose
      abnormalities. The prevalence of MS and its components is similar in treated and
      untreated HIV-positive patients.

PMID- 17514014
TI  - The relation between symptoms, viral load, and viral load set point in primary
      HIV infection.
AB  - OBJECTIVES: To examine the relation between symptoms, initial viral load, and
      viral load set point in primary HIV infection (PHI). DESIGN: Prospective cohort
      of patients with preseroconversion or recent seroconversion HIV infection
      (typically <60 days) in San Francisco. METHODS: Subjects were questioned about 21
      potential PHI symptoms at enrollment and were subsequently followed with viral
      load measures. RESULTS: The analysis included 57 subjects with preseroconversion
      HIV infection and 120 with recent seroconversion. In univariate analysis, most
      symptoms and the total number of symptoms were each associated with a
      significantly higher initial viral load. In stepwise multiple linear regression,
      however, only the number of symptoms was independently associated with a higher
      initial viral load, with an increase in the initial viral load of 0.08 log10 per
      additional symptom (P < 0.001). In univariate analysis, more PHI symptoms were
      associated with a higher viral load set point, but in a multivariable mixed
      effects model, this association was accounted for by the initial viral load,
      which was strongly correlated with viral load set point (R = 0.44, P < 0.001).
      CONCLUSIONS: A high initial viral load was associated with more symptoms during
      PHI. The strong correlation between initial HIV-1 RNA viral load levels and viral
      load set point suggests that early interactions between the HIV-1 virus and a new
      host, even before fully developed adaptive immune responses, are important in
      establishing viral load set point.

PMID- 17514015
TI  - Flash-heat inactivation of HIV-1 in human milk: a potential method to reduce
      postnatal transmission in developing countries.
AB  - BACKGROUND: Up to 40% of all mother-to-child transmission of HIV occurs by means
      of breast-feeding; yet, in developing countries, infant formula may not be a safe
      option. The World Health Organization recommends heat-treated breast milk as an
      infant-feeding alternative. We investigated the ability of a simple method, flash
      heat, to inactivate HIV in breast milk from HIV-positive mothers. METHODS: Ninety
      eight breast milk samples, collected from 84 HIV-positive mothers in a periurban
      settlement in South Africa, were aliquoted to unheated control and flash-heating.
      Reverse transcriptase (RT) assays (lower detection limit of 400 HIV copies/mL)
      were performed to differentiate active versus inactivated cell-free HIV in
      unheated and flash-heated samples. RESULTS: We found detectable HIV in breast
      milk samples from 31% (26 of 84) of mothers. After adjusting for covariates,
      multivariate logistic regression showed a statistically significant negative
      association between detectable virus in breast milk and maternal CD4+ T
      lymphocyte count (P=0.045) and volume of breast milk expressed (P=0.01) and a
      positive association with use of multivitamins (P=0.03). All flash-heated samples
      showed undetectable levels of cell-free HIV-1 as detected by the RT assay
      (P<0.00001). CONCLUSIONS: Flash-heat can inactivate HIV in naturally infected
      breast milk from HIV-positive women. Field studies are urgently needed to
      determine the feasibility of in-home flash-heating breast milk to improve infant
      health while reducing postnatal transmission of HIV in developing countries.

PMID- 17514016
TI  - Prevalence of HIV-1 drug resistance in treated patients: a French nationwide
      study.
AB  - BACKGROUND: Surveillance of HIV-1 drug resistance in antiretroviral-treated
      patients is important from the public health perspective of the spread of
      resistance and to evaluate the proportion of patients for whom new drugs are
      needed. METHODS: Patients were consecutively included in 28 centers in France and
      1 center in Switzerland if they had a viral load measurement performed in June
      2004, with a result >or=1,000 copies/mL. Reverse transcriptase, protease, and
      gp41 genes were sequenced, and resistance mutations were reported as listed on
      the Web site ( www.iasusa.org). The genotypic resistance results were interpreted
      by the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS)
      and Stanford algorithms. RESULTS: The 498 patients included had been exposed to 9
      (interquartile ratio [IQR]: 6 to 12) antiretroviral drugs. Patients' viruses
      harbored 4 nucleoside reverse transcriptase inhibitor (IQR: 1 to 6) and 4
      protease inhibitor (PI; IQR: 2 to 8) resistance mutations, whereas 44% had at
      least 1 nonnucleoside reverse transcriptase inhibitor resistance mutation. The
      frequency of resistance to at least 1 drug was 88% with the ANRS algorithm and
      83% with the Stanford algorithm. The frequencies of complete resistance to 1, 2,
      and 3 classes of drugs were 37%, 15%, and 4%, respectively, with the ANRS
      algorithm and 27%, 23%, and 24%, respectively, with the Stanford algorithm. The
      most important differences between algorithms were for PIs. Using the ANRS
      algorithm and extrapolation on the whole French database, 19% of all treated
      patients could contribute to the spread of resistance and 4% had complete
      resistance to 2 classes of antiretroviral drugs. CONCLUSIONS: The observed
      patterns of resistance are linked to a long-lasting history of antiretroviral
      therapy. The frequency of multiresistance can vary according to the
      interpretation systems.

PMID- 17514017
TI  - Development of an HIV-1 reference panel of subtype B envelope clones isolated
      from the plasma of recently infected individuals.
AB  - We have developed an HIV-1 reference panel of 20 subtype B envelope clones
      isolated from the plasma of recently infected individuals. It is widely accepted
      that a prophylactic vaccine against HIV-1 requires the development of novel
      immunogens that are capable of eliciting broadly protective neutralizing antibody
      responses. Historically, patient serum has been screened for such antibodies by
      assaying against laboratory strains, but these viruses typically have increased
      neutralization sensitivity compared with primary isolates. To create a more
      standardized and relevant assay system for vaccine evaluation, we have developed
      a panel of primary envelopes derived from the plasma of individuals with
      documented acute/early subtype B HIV-1 infection occurring between 2000 and 2004.
      The HIV-1 envelopes from this panel vary in mode of transmission, coreceptor
      tropism, fusogenicity, and overall sensitivity to neutralization. These envelope
      sequences represent a broad spectrum of subtype B genetic diversity with an
      average pairwise genetic distance of 12% and a range from 10% to 19%. This well
      characterized HIV-1 envelope panel should be a valuable resource for optimizing
      and standardizing vaccine assessment and improving vaccine design.

PMID- 17514018
TI  - Genetic characterization of HIV-1 strains circulating in Kazakhstan.
AB  - To determine the HIV-1 genetic diversity in Kazakhstan, 85 blood samples from HIV
      seropositive donors were collected between 2001 and 2003. The study population
      consisted of 91.8% injecting drug users (IDUs); the remainder was infected
      sexually or iatrogenically. A genomic region that included part of the polymerase
      gene was sequenced for all 85 samples, and from these, 6 samples were randomly
      selected for nearly full genome sequencing. Subtype A was the most common genetic
      form (94.1%), followed by CRF02_AG (4.7%) and subtype C (1.2%). All subtype A
      sequences clustered closely with samples from countries of the former Soviet
      Union (FSU). From these sequences, 47 (58.8%) presented the secondary protease
      inhibitor mutation V77I that has been linked to a genetic lineage in the FSU
      epidemic. In addition, most had the other 2 mutations that characterize the "V77I
      haplotype." All 6 nearly full-length sequences were subtype A and clustered with
      other FSU strains. The CRF02_AG strains from this population clustered with
      strains from Uzbekistan, reflecting the spread of the CRF02_AG epidemic in
      Central Asia. The HIV epidemic in Kazakhstan is predominantly in IDUs and is
      indigenous to the geographic region, and most of the strains are genetically
      similar to those circulating in the FSU and other parts of Central Asia.

PMID- 17514019
TI  - Patients' perceptions of highly active antiretroviral therapy in relation to
      treatment uptake and adherence: the utility of the necessity-concerns framework.
AB  - OBJECTIVE: To test the utility of the necessity-concerns framework in predicting
      highly active antiretroviral therapy (HAART) uptake and adherence. METHODS: This
      was a prospective follow-up study. Consecutive patients who were not currently
      receiving HAART were referred by their HIV physician. Immediately after a
      recommendation of HAART, patients completed the Beliefs about Medicines
      Questionnaire assessing their perceptions of personal necessity for HAART and
      concerns about potential adverse effects. The influence of these beliefs on the
      decision to accept or decline HAART and adherence 12 months later were assessed.
      RESULTS: One hundred fifty-three participants were given a recommendation of
      HAART, and 136 (88.9%) returned completed questionnaires. Thirty-eight
      participants (28%) initially rejected the treatment offer. Uptake of HAART was
      associated with perceptions of personal necessity for treatment (odds ratio
      [OR]=7.41, 95% confidence interval [CI]: 2.84 to 19.37) and concerns about
      potential adverse effects (OR=0.19, 95% CI: 0.07 to 0.48). There was a
      significant decline in adherence over time. Perceived necessity (OR=2.19, 95% CI:
      1.02 to 4.71) and concerns about adverse effects (OR=0.45, 95% CI: 0.22 to 0.96),
      elicited before initiating HAART, predicted subsequent adherence. These
      associations were independent of clinical variables and depression. CONCLUSIONS:
      The necessity-concerns framework is a useful theoretic model for understanding
      patient perspectives of HAART and predicting uptake and adherence, with
      implications for the design of evidence-based interventions.

PMID- 17514021
TI  - Burn state of the science research conference concluding remarks.

PMID- 17514020
TI  - Is the glass really half empty? A closer look at the TBSA data in the National
      Burn Repository.

PMID- 17514023
TI  - Overview of day 2: burn rehabilitation.

PMID- 17514024
TI  - Burn research state of the science: introduction.

PMID- 17514025
TI  - Building the research teams of the future: changing the paradigm.

PMID- 17514026
TI  - Research funding opportunities.

PMID- 17514027
TI  - Journal editors forum.

PMID- 17514028
TI  - The burn survivor perspective.

PMID- 17514029
TI  - Restoration of function.

PMID- 17514030
TI  - Hand burns.

PMID- 17514031
TI  - Psychological health and function after burn injury: setting research priorities.

PMID- 17514032
TI  - Traumatic osteomyelitis of the femur treated with distraction osteogenesis
      without surgical bone resection: a case report.

PMID- 17514033
TI  - Repair of a torn thoracic aorta, associated with an aberrant left vertebral
      artery.

PMID- 17514034
TI  - Serial angiographic evolution and regression of traumatic aneurysm of the
      internal carotid artery associated with a carotid-cavernous fistula.

PMID- 17514035
TI  - Survival following combined intrapericardial inferior vena cava and thoracic
      aortic injury caused by blunt trauma.

PMID- 17514036
TI  - Hemorrhage in a pre-existing ureteropelvic junction obstructed kidney: an unusual
      cause of duodenal obstruction after blunt abdominal trauma.

PMID- 17514037
TI  - Quadriparesis after a fall: hypokalemia can mimic acute spinal cord injury.

PMID- 17514038
TI  - Unusual dislocation of the elbow in a child--review of literature.

PMID- 17514039
TI  - Sleeve fracture of the patella: an unusual mechanism of injury.

PMID- 17514040
TI  - Early detection of fractures with low-dose digital X-ray images in a pediatric
      trauma unit.

PMID- 17514041
TI  - Bilateral traumatic long thoracic nerve palsies.

PMID- 17514042
TI  - Tibial nails for femoral shaft fractures in large adolescents with open femoral
      physes.

PMID- 17514043
TI  - Traumatic cervical hematomyelia: report of a rare spinal cord injury without
      radiographic abnormality.

PMID- 17514044
TI  - Extensive subcutaneous emphysema and pneumomediastinum associated with blowout
      fracture of the medial orbital wall.

PMID- 17514045
TI  - Close proximity blast injury patterns from improvised explosive devices in Iraq:
      a report of 18 cases.

PMID- 17514046
TI  - Patent foramen ovale closure before orthopedic trauma surgery to reduce risk of
      recurrent systemic fat embolism.

PMID- 17514047
TI  - External fixation for temporary stabilization and wound management of an open
      pelvic ring injury with extensive soft tissue damage: case report and review of
      the literature.

PMID- 17514048
TI  - Successful endovascular repair of a ruptured aortic pseudoaneurysm after
      swallowing sulfuric acid.

PMID- 17514049
TI  - Central pulmonary artery embolism after perihepatic packing because of liver
      trauma.

PMID- 17514050
TI  - Early progression of an isolated ventricular septal defect after blunt trauma.

PMID- 17514051
TI  - Perimortem cesarean section after utilization of surgeon-performed trauma
      ultrasound.

PMID- 17514052
TI  - Transperineal thoracic impalement without diaphragmatic injury.

PMID- 17514053
TI  - Intrapelvic penetration of the dynamic hip screw during removal: lesson learnt-
      always use a coupling screw.

PMID- 17514054
TI  - Blunt abdominal trauma leading to traumatic transection of the liver without
      massive hemorrhage.

PMID- 17514055
TI  - Penetrating injury to the intra-abdominal esophagus from a stab wound to the left
      flank.

PMID- 17514056
TI  - Gunshot abdominal wall injury reconstructed with an innervated latissimus dorsi
      free flap.

PMID- 17514057
TI  - Dislocation of all metatarsophalangeal joints caused by horse injury.

PMID- 17514058
TI  - Laparoscopy and the management of blunt bladder trauma.

PMID- 17514059
TI  - A nonfatal impalement injury of the thoracic descending aorta: a case report.

PMID- 17514060
TI  - Fat embolism syndrome: yes or no?

PMID- 17514061
TI  - Surgical stabilization of a rib fracture using an angle stable plate.

PMID- 17514062
TI  - Posttraumatic locked-in syndrome from a pontomedullary contusion: case report.

PMID- 17514063
TI  - Lipochoristoma of the cerebellopontine angle.

PMID- 17514064
TI  - Standard cochlear implantation of adults with residual low-frequency hearing:
      implications for combined electro-acoustic stimulation.
AB  - OBJECTIVE: This study compared preoperative and postoperative cochlear implant
      benefit in subjects with steeply sloping high-frequency hearing losses (HLs) who
      were implanted with standard long cochlear implant electrodes to: 1) determine
      the effect of etiology, 2) compare outcomes in studies exploring the use of
      combined electrical and acoustic stimulation, and 3) compare outcomes in patients
      implanted using standard criteria. STUDY DESIGN: Retrospective case review.
      SETTING: Tertiary referral center. PATIENTS: Nine adults with steeply sloping
      high-frequency congenital (n=2) or acquired (n=7) bilateral sensorineural HL. All
      pure-tone audiograms fit the criteria for trials of a short electrode aimed at
      preserving low-frequency acoustic hearing. INTERVENTION: Subjects received full
      insertion of a standard cochlear implant long electrode in the poorer ear. MAIN
      OUTCOME MEASURES: Preoperative versus postoperative audiograms, word and sentence
      recognition in quiet and noise. RESULTS: Patients with progressive acquired HLs
      experienced significantly improved speech understanding in quiet and in noise
      with the cochlear implant, especially when combined with hearing aid use in the
      contralateral ear. Patients with congenital HLs experienced little or no
      improvement in the implanted ear when tested with the implant alone, but achieved
      some benefit when the implant was combined with a hearing aid in the nonimplanted
      ear. CONCLUSION: Based on this small sample, patients with acquired steeply
      sloping high-frequency HLs obtain significant benefit from cochlear implantation
      with standard long electrodes. In progressive losses, full insertion of a long
      electrode would be preferable to a short electrode because acoustic hearing may
      diminish over time. In contrast, patients with congenital losses may not benefit
      from long electrodes, and might be better served by implanting a short electrode,
      thereby allowing use of low-frequency acoustic stimulation.

PMID- 17514065
TI  - Autonomic nervous system function in chronic dizziness.
AB  - OBJECTIVE: The goals of this study were to validate the clinical diagnosis of
      autonomic dizziness as a cause of chronic nonvertiginous dizziness that may be
      exacerbated by physical exertion or orthostatic challenges, estimate its
      prevalence in a tertiary referral population, and investigate the usefulness of
      three autonomic challenges as objective tests for this condition. STUDY DESIGN:
      Laboratory investigation of autonomic activity. SETTING: Tertiary care balance
      center. PATIENTS: Fifteen men and women with symptoms indicative of autonomic
      dizziness. Subjects with other causes of dizziness, histories of syncope, or
      psychiatric disorders were excluded. INTERVENTIONS: Autonomic tests included 45
      minutes of head upright tilt (HUT), 20 minutes of 5% CO2 inhalation and then HUT,
      and 2 minutes of voluntary hyperventilation and then HUT. MAIN OUTCOME MEASURES:
      Patterns of cardiovascular and respiratory responses and subjective ratings of
      dizziness, autonomic symptoms, and anxiety during autonomic challenges. RESULTS:
      Twelve subjects had evidence of autonomic dysfunction, including 10 with abnormal
      heart rate, blood pressure, or respiratory responses to HUT. Two other subjects
      had prolonged hypocarbia after voluntary hyperventilation. Many of these
      abnormalities would have been missed by current autonomic testing paradigms. In
      one subject, CO2 inhalation revealed latent anxiety. In two subjects, the
      presence of high symptom ratings without objective autonomic dysfunction prompted
      a successful search for other diagnoses. CONCLUSION: Study results validated the
      clinical syndrome of autonomic dizziness. Autonomic testing protocols may have to
      be updated to detect clinically relevant abnormalities in patients with
      dizziness.

PMID- 17514068
TI  - Response: images and interventions.

PMID- 17514067
TI  - Imaging the addicted human brain.
AB  - Modern imaging techniques enable researchers to observe drug actions and
      consequences as they occur and persist in the brains of abusing and addicted
      individuals. This article presents the five most commonly used techniques,
      explains how each produces images, and describes how researchers interpret them.
      The authors give examples of key findings illustrating how each technique has
      extended and deepened our knowledge of the neurobiological bases of drug abuse
      and addiction, and they address potential clinical and therapeutic applications.

PMID- 17514069
TI  - Assessing organizational functioning as a step toward innovation.
AB  - Innovate and adapt are watchwords for substance abuse treatment programs in
      today's environment of legislative mandates, effective new interventions, and
      competition. Organizations are having to evolve - ready or not - and those that
      are ready have superior chances for success and survival. The Texas Christian
      University Organizational Readiness for Change (ORC) survey is a free instrument,
      with supporting materials, that substance abuse treatment programs use to assess
      organizational traits that can facilitate or hinder efforts at transition. This
      article presents organizational change as a three-stage process of adopting,
      implementing, and routinizing new procedures; describes the use of the ORC; and
      outlines a step-by-step procedure for clearing away potential obstacles before
      setting forth on the road to improved practices and outcomes.

PMID- 17514070
TI  - One program's transition to research-based strategies for treating
      methamphetamine abuse.
AB  - Prairie Ridge Addiction Treatment Services turned to SAMHSA's Treatment
      Improvement Protocol (TIP) 33, "Treatment for Stimulant Use Disorders," to try to
      establish more effective practices for their fast-growing population of
      methamphetamine-addicted clients. Six years later, Prairie Ridge's executive
      director says that adopting the TIP's client-based treatment philosophy has
      enhanced the program's accessibility and results, not only for stimulant-abusing
      clients, but others as well. In this article he recounts how the TIP contents
      meshed with Prairie Ridge's preexisting treatment philosophy and practices; what
      they adopted and what they adapted from the TIP and why; counselors' responses
      during the transition; and outstanding issues.

PMID- 17514071
TI  - Response: TIPsters weigh in: putting good science to work.

PMID- 17514072
TI  - Quality and performance improvement: what's a program to do?
AB  - A confluence of forces is challenging traditional approaches to issues of quality
      in substance abuse care. The availability of effective, research-based
      interventions, the Federal emphasis on performance measurement and outcomes, and
      national initiatives to improve quality and data infrastructure are driving a
      transition from a static, compliance-oriented approach to a more dynamic
      performance improvement model. This new way of achieving and documenting quality
      will produce better outcomes for consumers and greater confidence in the value of
      substance abuse services, but first it will require new behaviors from all
      parties involved in the delivery of substance abuse prevention and treatment
      services. This article describes some of the shifts already under way and offers
      advice on how organizations can get ready for the coming changes.

PMID- 17514073
TI  - Response: setting the stage for improvement and accountability.

PMID- 17514074
TI  - Attending to emotional cues for drug abuse: bridging the gap between clinic and
      home behaviors.
AB  - Classical conditioning models of addiction provide keys to understanding the
      vexing discrepancy between substance abuse patients' desire to abstain when they
      are in therapy sessions and their tendency to relapse. Experiments using these
      models demonstrate the power of environmental relapse cues and support clinical
      approaches, including active exposure, aimed at helping patients recognize and
      withstand them. Internal cues, including emotions and somatic states such as
      withdrawal, can trigger urges as powerfully as external cues such as people,
      places, and things associated with prior abuse. The authors describe a cognitive
      behavioral therapy approach that focuses on identifying and actively inducing
      each patient's high-risk emotions, then helping him or her develop and practice
      healthy responses. Clinical trials support the approach for patients with panic
      disorder who have trouble discontinuing benzodiazepines, and early trials suggest
      it may be useful for patients addicted to other drugs as well.

PMID- 17514075
TI  - Response: disconnects, triggers, and two-edged swords.

PMID- 17514076
TI  - Same behaviors, different HIV/STD risks for Whites, African-Americans.

PMID- 17514077
TI  - What is the self? A psychobiological perspective.
AB  - Philosophers have long struggled with questions about the nature of personal
      identity and of the self, with some viewing the self as a transcendent entity,
      and others arguing that the self is a constructed fiction. An approach based in
      cognitive-affective neuroscience emphasizes that self-related structures and
      processes are based in the brain-mind, and emerge within the social processes of
      human development. Alterations in such structures and processes are present in a
      wide range of neurological and psychiatric disorders, and neuropsychiatric lesion
      and functional brain imaging studies have led to more detailed awareness of the
      precise neuronal circuitry underlying self-representations. A cognitive-affective
      neuroscience approach provides a conceptual basis from which clinical research
      can further explore how best to assess and treat a wide range of disruptions to
      the self.

PMID- 17514078
TI  - Comprehensive treatment of three patients with comorbid OCPD and ADHD.
AB  - Three patients were seen in an outpatient setting with work difficulties
      involving disorganization and task completion. They were evaluated and found to
      have significant symptoms of both attention-deficit/hyperactivity disorder,
      inattentive subtype and obsessive-compulsive personality disorder and were then
      treated with a creative combined behavioral and medication treatment, which
      emphasized the use of external aides (eg, paraprofessionals). Significant symptom
      reduction was observed as a result of this combined intervention.

PMID- 17514079
TI  - Obsessive-compulsive behavior spectrum: refining the research agenda for the DSM
      V.

PMID- 17514080
TI  - The relationship of body dysmorphic disorder and eating disorders to obsessive
      compulsive disorder.
AB  - Body dysmorphic disorder (BDD) and eating disorders are body image disorders that
      have long been hypothesized to be related to obsessive-compulsive disorder (OCD).
      Available data suggest that BDD and eating disorders are often comorbid with OCD.
      Data from a variety of domains suggest that both BDD and eating disorders have
      many similarities with OCD and seem related to OCD. However, these disorders also
      differ from OCD in some ways. Additional research is needed on the relationship
      of BDD and eating disorders to OCD, including studies that directly compare them
      to OCD in a variety of domains, including phenomenology, family history,
      neurobiology, and etiology.

PMID- 17514081
TI  - Obsessive-compulsive disorder: boundary issues.
AB  - The boundaries between obsessive-compulsive disorder (OCD) and other
      neuropsychiatric disorders remain unresolved and may well differ from one
      disorder to another. Endophenotypes are heritable, quantitative traits
      hypothesized to more closely represent genetic risk for complex polygenic mental
      disorders than overt symptoms and behaviors. They may have a role in identifying
      how closely these disorders are associated with another and with other mental
      disorders with which they share major comorbidity. This review maps the
      nosological relationships of OCD to other neuropsychiatric disorders, using OCD
      as the prototype disorder and endophenotype markers, such as cognitive, imaging,
      and molecular data as well as results from demographic, comorbidity, family, and
      treatment studies. Despite high comorbidity rates, emerging evidence suggests
      substantial endophenotypic differences between OCD and anxiety disorders,
      depression, schizophrenia, and addictions, though comparative data is lacking and
      the picture is far from clear. On the other hand, strong relationships between
      OCD, Tourette syndrome, body dysmorphic disorder, hypochondriasis, grooming
      disorders, obsessive-compulsive personality disorder, and pediatric autoimmune
      neuropsychiatric disorders associated with streptococcus are likely. Studies
      designed to delineate the cause, consequences, and common factors are a
      challenging but essential goal for future research in this area.

PMID- 17514082
TI  - Symptom dimensions in obsessive-compulsive disorder: implications for the DSM-V.
AB  - In the absence of definitive etiological markers of vulnerability or a unitary
      profile of pathophysiology for obsessive-compulsive disorder (OCD), obsessive
      compulsive (OC) symptom dimensions seem to offer a fruitful point of orientation.
      The complex clinical presentation of OCD can be summarized using a few consistent
      and temporally stable symptom dimensions. These can be understood as a spectrum
      of potentially overlapping features that are likely to be continuous with
      "normal" worries and extend beyond the traditional nosological boundaries of OCD.
      Although the understanding of the dimensional structure of obsessive-compulsive
      symptoms (OCS) is still imperfect, this quantitative approach to phenotypic
      traits has the potential to advance our understanding of OCD and may aid in the
      identification of more robust endophenotypes. Preliminary data suggest that these
      dimensional phenotypes may be useful in studies of the natural history, genetics,
      neurobiology, and treatment outcome of OCD. A dimensional approach is not
      mutually exclusive of other methods to parse the larger spectrum of disorders
      related to OCD. Thus far, age-of-onset of OCS and the individual's "tic-related"
      status seem to be particularly useful categorical distinctions. Finally, existing
      assessment methods are inadequate and new dimensional scales are needed to take
      full advantage of a dimensional approach in clinical and population-based
      studies.

PMID- 17514083
TI  - Obsessive-compulsive spectrum disorders: cross-national and ethnic issues.
AB  - Epidemiological and clinical data from a variety of cultural and geographic
      settings on obsessive-compulsive disorder (OCD), and many of the obsessive
      compulsive spectrum disorders, suggest that this is a group of disorders with a
      good degree of transcultural homogeneity. However, the content and themes that
      predominate in patients with these disorders, and the course of illness, can be
      shaped by cultural, ethnic, and religious experiences. Across cultures, OCD is
      commonly comorbid with mood, anxiety, and impulse-control disorders. However,
      little is known about the mechanisms by which culture and ethnicity may affect
      the expression of OCD and related disorders. Cross-national comparative studies
      exploring culturally influenced differences in clinical course, treatment
      outcome, including ethnogenetic differences in drug response, and prognosis are
      needed.

PMID- 17514153
TI  - Current acute care of intracerebral hemorrhage.
AB  - Intracerebral hemorrhage is the stroke subtype with the highest mortality rate
      (40% to 50%). Until the hypotheses investigating the amelioration of disease
      severity factors are completely tested and found to be correct, intracerebral
      hemorrhage will remain the leading cause of stroke morbidity and mortality in the
      United States. The acute management of intracerebral hemorrhage with particular
      emphasis on the evolving areas of probable therapeutic benefit, which are early
      stabilization, management of mass effect by intraventricular clot removal, and
      intracranial pressure management, are reviewed.

PMID- 17514152
TI  - Functional neuroimaging and repetitive transcranial magnetic stimulation in
      Parkinson's disease.
AB  - Functional neuroimaging provides insights into the pathogenesis of motor symptoms
      in Parkinson's disease (PD) and improves our understanding of both established
      neuromodulatory therapies such as deep brain stimulation (DBS) and potential ones
      such as repetitive transcranial magnetic stimulation (rTMS). Functional imaging
      studies can reveal the consequences of the dopaminergic lesion in PD among a
      widespread network of subcortical-cortical regions. Characteristic patterns of
      normal cortical brain activation for motor tasks are systematically altered in
      PD. Recent work has emphasized the task dependence of these changes and their
      gradual evolution over the course of the disease. Clinically relevant PD
      treatment with medications or DBS tends to normalize these patterns. In this
      context, rTMS is discussed as a potential noninvasive alternative for
      neuromodulation of cortical function. Although rTMS is not a current treatment,
      we review recent rTMS studies in PD that suggest its promise, illustrate how
      functional imaging can guide application of rTMS, and suggest that subcortical
      dopamine release could be an rTMS mechanism of action. The combination of rTMS
      and functional neuroimaging broadens our knowledge of functional cortical
      networks in PD, which can eventually provide physicians with pathophysiologic
      information about different PD treatment options and rationales for
      neuromodulatory interventions.

PMID- 17514155
TI  - Clinical neurology of insomnia in neurodegenerative and other disorders of
      neurological function.
AB  - Complaints of insomnia are prevalent in neurodegenerative and neurological
      disorders. Neurologists therefore must be aware of the underlying causes,
      pathophysiologic mechanisms, and potential interventions when encountering a
      patient with underlying neurological disorders who is also complaining of poor
      sleep and insomnia. This article describes the underlying pathophysiology,
      diagnostic approaches, and potential interventions for insomnia in the
      neurological patient. Clinicians need to recognize that insomnia in older
      patients with underlying neurological disorders is not only unique, but also
      complex, demanding comprehensive and careful evaluation and management. Treatment
      of insomnia should start by addressing nonpharmacologic options, including
      improvements in sleep hygiene, improving sunlight exposure during the day, and
      searching for underlying reversible causes, such as sleep apnea, restless legs
      syndrome, periodic leg movements, and circadian rhythm disturbances, all of which
      can precipitate insomnia when left untreated. Some patients may benefit from
      targeted and carefully tailored pharmacologic treatment. Successful amelioration
      of insomnia can ultimately be a very rewarding experience for the patient, family
      members, and the practitioner.

PMID- 17514156
TI  - Studies in neuropathy and myasthenic disorders. Highlights of the American
      Association of Neuromuscular and Electrodiagnostic Medicine Annual Meeting,
      October 11-14, 2006, Washington, DC.

PMID- 17514157
TI  - Anterior cingulate epilepsy in an 18-year-old woman.
AB  - Anterior cingulate epilepsy is a diagnostic and therapeutic challenge, with a
      broad range of nonspecific symptoms. Seizures can arise from any region of the
      anterior cingulate cortex (ACC) and manifest distinctive features based on the
      area of onset and pattern of spread. These features may provide insight as to the
      origin of the seizures, but because the ACC integrates information from several
      networks involving emotional and executive functions and has a diverse
      cytoarchitecture, functional-structural correlates are complex. Further, the
      location of the ACC within the interhemispheric fissure limits the capacity of
      scalp electrodes to record seizure activity from this region. This case review
      illustrates one part of the spectrum of cingulate epilepsy and discusses clinical
      features of the disorder.

PMID- 17514158
TI  - Should electroconvulsive therapy be given to patients with intracranial vascular
      lesions?
AB  - The risk of rupture and hemorrhage of intracranial vascular lesions during
      electroconvulsive therapy (ECT) is currently unknown. We describe 2 cases in
      which ECT was discontinued because of perceptual disturbances, confusion, and the
      subsequent discovery of intracranial angiomas. ECT has been associated with
      nonconvulsive status epilepticus and prolonged altered mental status following
      treatment, but there has been scant documentation of side effects associated with
      intracranial vascular malformations. We review the literature on ECT in patients
      with such lesions and present 2 cases in which lesions were found in the context
      of perceptual disturbances and altered states of consciousness following ECT.

PMID- 17514161
TI  - Restrainer of pelvis and lower limbs in thoracic and lumbar range of motion
      measurement--preliminary report.
AB  - BACKGROUND: Range of motion (ROM) is a parameter of prime importance for clinical
      assessment of spinal function. Many spinal ROM assessment techniques of varying
      reliability are currently in use. Immobilization of the pelvis and lower
      extremities improves control of the neutral position and decreases the error
      resulting from compensatory hip motion during measurement. To present a
      prototypic station for active 3-dimensional spinal ROM assessment; to analyze
      repeatability of measurements and reproducibility of the neutral position.
      METHODS: A quintuple 3-dimensional measurement of the lumbar and thoracic active
      range of motion in 12 healthy volunteers. RESULTS: The series of results obtained
      for each subject fulfilled the criteria of a normal distribution. The mean values
      of thoracic ROM were as follows: sagittal 40.1 degrees (SD=5.56 degrees; mean
      coefficient of variation CV=13.88%); horizontal 75.2 degrees (SD=6.01 degrees;
      CV=7.99%); frontal 34.0 degrees (SD=3.01 degrees; CV=8.84%). The mean values of
      lumbar ROM were as follows: sagittal 112.0 degrees (SD=4.13; CV=3.68%);
      horizontal 14.8 degrees (SD=3.77 degrees; CV=25.45%); frontal 67.6 degrees
      (SD=2.72 degrees; CV=4.03%). Inter-class correlation coefficients for particular
      subjects ranged between 0.95 and 0.99 (p<0.0001). Mean reproducibility of the
      neutral position was 1.08 degrees-2.63 degrees in thoracic spine and 1.23 degrees
      2.31 degrees in lumbar spine. Comparison of the results with literature data
      revealed good neutral position reproducibility and high values of inter-class
      correlation coefficients in the present study. Potential reasons for assessment
      errors are discussed. Recommendations for the construction of an improved
      immobilizer for diagnostic purposes are presented. CONCLUSIONS: Validated spinal
      ROM measurements are useful in monitoring patients with musculoskeletal
      disorders. Immobilization of the pelvis and lower limbs improves repeatability of
      thoracic and lumbar ROM assessment and reproducibility of a neutral position. The
      prototype enables highly repeatable measurements, but requires technical
      improvements.

PMID- 17514162
TI  - Mobility of cervical spine and postural equilibrium in patients with spinal
      overload syndrome.
AB  - BACKGROUND: The spinal overload syndrome develops as a result of the gradual
      wearing away of the structural elements of the spine due to loads exceeding their
      endurance strength in the setting of reduced adaptability. The aim of the
      investigation was to study the limitation of mobility in the cervical spine and
      determine the effect of the spinal overload syndrome on postural equilibrium.
      MATERIAL AND METHODS: The study enrolled 27 patients with signs of overload of
      the cervical spine. Postural equilibrium was measured by stabilography. Range of
      motion in the cervical spine was also evaluated. CONCLUSIONS: The investigations
      of spinal mobility indicate a disturbance of muscular equilibrium. Most of the
      patients suffered from Lewit's upper crossed syndrome. The disturbance of
      postural equilibrium is of functional origin.

PMID- 17514163
TI  - Principles of neuro mobilization for treating musculoskeletal disease.
AB  - Neuro mobilization is a method of conservative treatment of disorders of neural
      tissue. The rationale for using neuro mobilization in the treatment of
      musculoskeletal conditions is based on in vivo and in vitro studies which point
      to a high efficacy of neuro mobilization procedures. Appropriate use of neuro
      mobilization procedures depends on excellent knowledge of normal and pathological
      anatomy, differences between individual etiological factors, development of
      disease and symptom variability. The present paper familiarizes the reader with
      evidence-based conservative treatment of musculoskeletal conditions by neuro
      mobilization.

PMID- 17514164
TI  - Computerized tomography evaluation of cortical bone properties in the tibia.
AB  - BACKGROUND: Tibia shaft fractures are among the most common fractures. However,
      the incidence of tibia fractures does not increase in the elderly. Osteoporotic
      bone resorption is possibly compensated for by periosteal apposition, which
      improves the mechanical properties of the bone. The purpose of this study was to
      identify a correlation between geometric indices of transverse bone scans and
      radiologic bone density based in CT studies. MATERIAL AND METHODS: 12 human
      cadaver tibiae were CT examined. Radiological density in Hounsfield units was
      evaluated in transverse bone scans taken at the junction of the distal and middle
      third of the tibial shaft. The average and maximum radiological density and area
      of cortical bone were evaluated. RESULTS: Average radiological bone density
      decreased with age. This was not accompanied by a corresponding increase in
      cortical bone area. CONCLUSION: The study did not provide direct confirmation
      that age-related osteoporotic bone resorption is compensated for by periosteal
      apposition.

PMID- 17514166
TI  - Orthopaedic problems in patients affected by alkaptonuria. A case report.
AB  - Alkaptonuria is a rare congenital metabolic disorder. A defect of the enzyme
      homogentisic oxidase results in a block of the metabolic pathway of the amino
      acids phenylalanine and tyrosine. Deposits of homogentisic acid polymers in
      connective tissue cause various organ manifestations, including musculoskeletal
      symptomatology. A 66 year-old woman was twice admitted to our Department because
      of progressive knee and low back pain. Physical examination and accessory
      investigations confirmed that her various complaints were caused by underlying
      alkaptonuria. We use this case and a review of literature to discuss orthopaedic
      problems in patients with alkaptonuria and describe the cardinal signs and
      symptoms of this disease, its diagnosis and treatment.

PMID- 17514167
TI  - Interbody fusion and transpedicular fixation in the treatment of
      spondylolisthesis.
AB  - BACKGROUND: This is a retrospective analysis of long-term results of treatment of
      dysplastic, isthmic and degenerative spondylolisthesis with interbody fusion and
      transpedicular screw fixation. MATERIAL AND METHODS: Twenty-one patients
      underwent interbody fusion with the "Bialstab" transpedicular system. Anterior
      lumbar interbody fusion (ALIF) was subsequently performed in 2 patients. In the
      remaining patients, posterior lumbar interbody fusion (PLIF) was performed
      following interbody fusion in the same session. Mean follow up was 22.4 months.
      Results were evaluated on the basis of a physical examination, the Oswestry
      questionnaire and the VAS back pain score. Radiologic assessment was based on
      targeted lateral radiographs to the stabilized segment. RESULTS: The post
      operative wound healed without complications in all patients. Clinical outcomes
      at follow-up were rated as good (10), quite good (9) and poor (2). The average
      Oswestry score was 14 (range 0-30). The mean VAS score at follow-up was 2.9
      (range 0-8). Anatomical slip reposition was performed in 2 patients, partial
      reposition in 11 patients, and 8 patients were treated with in situ fusion.
      Radiological evaluation revealed fusion in 17 patients. CONCLUSIONS: 1.
      Transpedicular fixation with interbody fusion is an effective technique for the
      treatment of spondylolisthesis. 2. Partial reposition of spondylolisthesis with
      neural decompression makes it possible to avoid neurological complications. 3.
      The "Bialstab" fixation system fulfills the criteria for good transpedicular
      stabilization.

PMID- 17514168
TI  - A protocol of rehabilitation after ACL reconstruction using a hamstring autograft
      in the first month after surgery--a preliminary report.
AB  - BACKGROUND: The purpose of this paper is to present a protocol of rehabilitation
      after ACL reconstruction using a hamstring autograft in the first month after
      surgery. The program enables the patient to return early to everyday activities
      (school, sedentary work) without crutches or a stabilizer. MATERIAL AND METHODS:
      The program has been developed in accordance with rehabilitation protocols
      employed at Karolinska Institute in Sweden and Prof. Shelbourne's Clinic in the
      USA. The study group included 31 patients (18 men and 13 women). RESULTS:
      Patients rehabilitated in the Department according to our program achieved stable
      gait patterns and were able to step up and down within four to seven weeks.
      CONCLUSIONS: Early patient mobilization after ACL reconstruction is possible and
      does not cause any negative effects provided that the patient, doctor and
      physiotherapist cooperate very closely.

PMID- 17514169
TI  - Current trends in total hip arthroplasty.
AB  - After 20 years of application, with excellent short-term and long-term results,
      uncemented total hip arthroplasty (THA) is now generally regarded as the standard
      procedure for younger patients undergoing THA. However, expectations regarding
      hip replacement are continuously rising, along with the increasing number of
      young and active patients undergoing hip arthroplasty: a complication rate,
      including postoperative dislocation, close to zero, faster postoperative
      rehabilitation, low wear even in active patients, high durability and long term
      survival, etc. Demographic changes in aging societies are also leading to an
      increased need for cost-effective THA for the low-demand trauma patient. For high
      demand patients, modern THA bearings, such as ceramic-ceramic articulations and
      other improved PE and metal materials, provide high durability and low wear, if
      the components are properly aligned. Navigation technology has been introduced in
      THA to ensure perfect component positioning without outliers and concomitant risk
      of increased wear and implant failure. Minimally and less invasive approaches are
      becoming increasingly popular in order to facilitate rehabilitation and fast
      track surgery in younger patients. Navigation provides assistance for implant
      positioning in procedures with limited surgical exposure and visibility. New bone
      preserving implants, such as surface replacement or short-stemmed femoral shaft
      prostheses, have been introduced especially for younger patients. Some of these
      new procedures are still under development,and the long-term results of new
      implant concepts have to be evaluated over the next decades. Not every modern
      concept will likely stand the test of time, but some will be beneficial for
      patients undergoing total hip arthroplasty in the future.

PMID- 17514170
TI  - Minimally invasive techniques in total hip replacement--our clinical experience.
AB  - The article presents the general concept of minimally invasive surgery, including
      theoretical benefits and risks. The indications, contraindications, technical
      requirements and necessary precautions are discussed. An overview of different
      surgical approaches is presented together with a detailed description of the
      surgical technique of minimally invasive cementless total hip replacement that is
      used at the Department of Orthopedics and Traumatology of Locomotor System,
      Medical University of Warsaw. Techniques for enhancing the precision of placement
      of prosthetic elements and leg length equalization used in clinical practice are
      also presented.

PMID- 17514171
TI  - Less invasive posterior surgical approach for hip joint replacement-
      complications and limitations.
AB  - BACKGROUND: We attempted to analyse the difficulties and risk of complications
      associated with total hip replacement using a limited posterior approach and
      standard instrumentation. MATERIAL AND METHODS: A series of 85 consecutive cases
      (47 females and 38 males; age range 22-87 years; mean age: 65.6 +/- 10.4) of
      total hip replacement using a modified Gibson approach were analyzed
      prospectively. Bilateral surgery was performed in 7 patients. There were 44 non
      cemented arthroplasties. Body mass index varied from 22 to 36 (body weight 78-104
      kg) and the length of the operative wound varied from 6.5 to 14 cm (mean 9.8 +/-
      1.3 cm). The wound was 14 centimeters long in six subjects with a BMI of 35-36.
      The procedure was performed in a lateral decubitus position using an
      appropriately limited posterior approach. After careful coagulation of blood
      vessels surrounding the base of the femoral head posteriorly, the obturator and
      gemelli tendons and the posterior part of the joint capsule were cut through as
      close to the femoral attachment (T) as possible. This made it possible to
      dislocate the joint posteriorly. Further stages of the procedure were performed
      in a typical manner, with special attention paid to the preservation of the
      tendon of the piriformis muscle. Continuity of the muscle was re-examined
      following the reposition of the artificial joint. RESULTS: Two injuries to the
      piriform tendon were observed. Persistent bleeding from vessels surrounding the
      femoral neck base occurred in 5 patients while in four others there was transient
      paresis of the peroneal muscles and dorsal extensors of the ipsilateral foot,
      probably caused by extension of the sciatic nerve. There was one oblique fracture
      of the proximal femoral shaft. We did not observe significant errors in
      postoperative joint geometry. Mean intraoperative blood loss was 400 ml. We did
      not note postoperative dislocations or infections. CONCLUSIONS: On the basis of
      our observations of a series of 85 patients, minimizing the extent of the
      posterior surgical approach for hip joint replacement seems an attractive
      alternative to the classical extensive technique. Our material reveals a
      relatively high incidence of transient paresis of the peroneal part of the
      sciatic nerve. The introduction of appropriate instrumentation and the
      accumulation of experience will certainly decrease the risk of extension of the
      sciatic nerve in the operative wound.

PMID- 17514172
TI  - Minimally invasive total hip arthroplasty--our clinical experience.
AB  - BACKGROUND: Minimally invasive prosthetic hip surgery (MIS) attempts to minimise
      the extent of the operation. The aim of the study was to describe minimally
      invasive hip surgery and to present early clinical experience of the authors.
      MATERIAL AND METHODS: 41 minimally invasive hip replacements through a posterior
      approach were carried out at the Orthopaedic Department of the Postgraduate
      Medical Education Centre in Otwock between 2004 and 2006. 29 of those patients
      were included into the study, of whom 23 presented for follow-up. A control group
      consisted of 29 randomly selected patients operated on using the classical
      method. Patients qualified for MIS had a BMI below 30 and a structurally normal
      hip joint with a good range of motion. RESULTS: Early results were subjected to a
      statistical analysis of 20 parameters. CONCLUSION: 1. The analysis showed that
      statistically significant baseline differences between MIS and traditionally
      treated patients included only BMI scores, structure of the hip joint and range
      of motion. 2. Implantation of a hip endoprosthesis in a MIS procedure does not
      differ from the traditional operation utilising a posterior access except for
      skin incision length.

PMID- 17514173
TI  - Total hip arthroplasty through a minimally invasive lateral approach--our
      experience and early results.
AB  - BACKGROUND:  AIMS: Evaluation of: 1. early clinical and radiographic results of
      total hip arthroplasty (THA) through a standard lateral direct approach, 2. early
      clinical and radiographic results of THA through a minimal lateral approach, 3.
      comparison of the results of THA in these two groups. MATERIAL AND METHODS: 120
      THAs (60 cementless and 60 cemented) done in 120 patients due to degenerative
      changes were evaluated prospectively. 60 THAs were done through a minimal lateral
      approach and constituted a study group. 60 THAs were done through a direct
      lateral approach and constituted a control group. The mean age of the 120
      patients (98 women and 22 men) was 45 y.o. (range: 32-67 y.o.). The duration of
      follow-up in the study group was from 6 to 12 months (mean: 8.5 months). The
      duration of follow-up in the control group was from 10 to 16 months (mean: 10.5
      months). Mean preoperative functional status of the study group was 44.5 points
      according to the Harris hip score. Radiographic evaluation of the results was
      done according to the criteria of the Joint Committee of the Hip Society, AAOS
      and SICOT. RESULTS: 6 months after THA, clinical results were 92 pts in the study
      group and 88 pts in the control group. Radiographic outcomes were very good in
      all 120 patients from both arms: there were no differences between the control
      and study group. The incidence of complications was similar in both groups.
      CONCLUSIONS: Minimally invasive THA demonstrated its value in the treatment of
      degenerative changes of the hip joint with regard to short-term outcomes. The
      clinical and radiographic outcomes were comparable between the standard and
      minimally invasive approaches. Success with THA using a minimally invasive
      approach depends on excellent operative technique and experience with standard
      hip approaches rather than on the use of special instruments.

PMID- 17514174
TI  - MicroHip: a minimally invasive procedure for total hip replacement surgery using
      a modified Smith-Peterson approach.
AB  - This article presents an anterior, minimally invasive surgical approach to the
      hip joint, aligned along an inter-nervous plane. Positioning in lateral decubitus
      position on a regular operation table obviates the need for a special orthopedic
      or fracture table. Traction is not applied. Most of the instruments used for this
      procedure are standard instruments for reaming of the acetabulum and positioning
      of the cup; specific, angulated instruments are recommended at least for obese
      patients. Using an incision of < 6-8 cm, this MI approach provides a perfect view
      of the acetabulum and proximal femur,including natural landmarks for proper
      implant positioning. The approach follows the gap between the tensor muscle and
      the gluteus medius muscle, using part of the anterior ilo-femoral Smith-Peterson
      approach. No tendons or muscles are cut or detached. The joint capsule is split
      and left in place. The hip joint is not dislocated; we perform the osteotomy of
      the femoral neck in situ. To date we have performed several hundred MicroHip
      operations, with no nerve lesions or trochanter fractures. Definitive results are
      not yet available, but our experience to date shows that this method can be used
      with virtually any patient, while such factors as hospitalization time, pain,
      blood loss and work incapacity can be cut almost in half. The MicroHip technique,
      used by an increasing number of clinics around the world, can be successfully
      applied by good surgeons after suitable training.

PMID- 17514175
TI  - Zone 1 extensor tendon lesions: current treatment methods and a review of
      literature.
AB  - The treatment options for the soft-tissue mallet finger, both acute and chronic,
      continue to generate a certain degree of controversy. Priority should always be
      given to conservative management of these injuries. This translates into a 6-to-8
      week period of uninterrupted immobilization of the DIP joint with an external
      splint. Splinting has been shown to be highly effective and safe for both acute
      and chronic lesions. Even in the presence of an open injury, the value of
      splinting should be appreciated by the practitioner. The conversion of an acute
      closed, soft-tissue injury to an open one is to be discouraged,due to
      unacceptable complication rates. When surgery is contemplated, in a selected
      group of patients, the first option advocated by most authors is the placement of
      a trans-articular Kirschner wire at the DIP joint and/or conjoint tendon
      advancement. If external splinting fails in an acute injury, an argument can
      certainly be made for a second trial of conservative management. It has been
      found that some patients will not tolerate a second period of immobilization, and
      in most such cases surgery is offered. In summary, mallet injuries are best
      treated using closed, nonoperative techniques. The period of time after injury
      for which this conservative treatment can be prolonged and still be effective is
      being extended, and the absolute outside time limit remains unknown. Surgical
      treatment should be reserved for mallet fractures, and in such cases Bunnel's
      pull-out suture is recommended. Finger rehabilitation is an indispensable part of
      any method of treatment.

PMID- 17514176
TI  - Senescence of osteogenic cells. Review.
AB  - In older individuals the regeneration of bone tissue is delayed due to the
      diminished activity of osteoblasts, while osteogenic potency of human bone marrow
      stromal cells, also capable of forming bone, does not change with age. The number
      of osteoprogenitor cells is not reduced in ageing subjects, but their
      proliferating rate and the activity of their derivatives--osteoblasts, is
      markedly diminished, since the self-renewing potential of these cells is
      hindered. The senescence of osteoblasts in ageing people is also accelerated.
      Changes within the bone marrow microenvironment reduce osteogenic potential of
      osteoprogenitor cells leading to impaired bone formation seen in senility, while
      the potency for ectopic osteogenesis does not change with age. This review
      summarizes documented mechanisms of changes in osteogenic activity of cells in
      elderly.

PMID- 17514177
TI  - Entrapment of the suprascapular nerve: anatomy, etiology, diagnosis, treatment.
AB  - Entrapment of the suprascapular nerve is a rare peripheral neuropathy, which can
      be easily overlooked in the differential diagnosis of shoulder pain and
      dysfunction. Entrapment of the suprascapular nerve can occur at different
      locations along the pathway of the nerve. The primary symptoms are pain,
      weakness, and atrophy of the supraspinate and infraspinate muscles. Differential
      diagnosis should include brachial plexopathy, disorders of the cervical spine,
      cervical discopathy, glenohumeral pathology, tendonitis, and rotator cuff tear.
      Accurate diagnosis facilitates appropriate and timely treatment.

PMID- 17514178
TI  - Results of operative treatment for ulnar neuropathy in patients with a history of
      fracture of the lateral part of the humeral condyle in childhood.
AB  - BACKGROUND: Fractures of the lateral part of the humeral condyle in childhood
      very often go undetected and are treated incorrectly, giving rise to numerous
      late complications. The study evaluated the outcomes of treatment of ulnar
      neuropathy secondary to a fracture of the lateral part of the humeral condyle in
      childhood. MATERIAL AND METHODS: The study enrolled 12 patients aged 28-58 who
      had suffered fractures of the elbow at between 2 and 14 years of age. Arthrosis
      and a valgus deformity of the joint, contractures in flexion and extension of the
      elbow as well as ulnar neuropathy were observed after an average of about 30
      years after the fracture. The patients accepted posttraumatic deformation of the
      axis and contractures of the elbow. The indication for operative treatment was
      the presence of signs of ulnar neuropathy. The treatment consisted in anterior
      transposition of the nerve. Postoperative follow-up lasted from 4 to 23 years.
      RESULTS AND CONCLUSIONS: The long-term sequelae of these fractures are a valgus
      deformity of the elbow, arthrosis of the joint and neuropathy of the ulnar nerve.
      Ulnar nerve transposition relieves the patients from nerve compression symptoms
      arising at this level.

PMID- 17514179
TI  - Outcome in corrective osteotomy for malunited distal radius fractures.
AB  - BACKGROUND: This article reports outcome in osteotomy for malunion of distal
      radius fractures. MATERIAL AND METHODS: We evaluated 12 patients with distal
      radius malunion (mean age 54), who were treated with corrective osteotomy. Wrist
      motion and grip strength were evaluated, along with examination of pre and post
      osteotomy radiographs. The indications for corrections were degree of deformity,
      limitation of function, pain, and the appearance of the wrist. RESULTS: The
      radiographic evaluation proved that the restoration of the normal anatomic
      relationship between the distal radius and ulna leads to significant improvement
      of the function of the hand, as measured by range of motion and grip strength.
      CONCLUSION: Osteotomy of the distal radius in cases of malunion gives favorable
      outcomes.

PMID- 17514180
TI  - Surgical treatment of articular calcaneal fractures.
AB  - BACKGROUND: Although Leriche (in 1921) and Judet (in 1954) introduced screw or
      plate fixation of the broken calcaneus, surgical treatment using open anatomical
      reduction and stable internal osteosynthesis only appeared in the early 1980s.
      This was made possible by the introduction of imaging methods such as CT, which
      allowed for better detection of the fracture pathology and provided the basis for
      new surgical strategies, e.g. anatomically-shaped calcaneal plates, available
      since the early 1990s. MATERIAL AND METHODS: During a 3-year period (2002-2005)
      the authors operated 23 dislocated calcaneal fractures (19 men, 4 women, 19-57
      years of age) involving the posterior calcaneo-talar joint (Sanders II and III
      according to CT-based classification). Treatment involved open reduction and
      internal fixation of the calcaneus through an extended lateral approach. Fixation
      was performed using lag screws and a reconstruction plate. We describe both the
      anatomic results (evaluation of the posterior articular surface of the calcaneus
      and the Bohler angle) and the functional outcome, using the Creighton-Nebraska
      system. RESULTS: In this prospectively evaluated group we achieved 12 good and 11
      very good anatomical results, and 2 fair, 16 good and 5 very good functional
      outcomes at follow-up (at least one year after surgery). Infections occurred in 3
      cases. CONCLUSIONS: The treatment option described here requires careful
      preoperative planning, with evaluation of the fracture pattern and patient
      condition, and good surgical expertise, but it provides good medium-term (1-3
      years) outcome. The presence ofa good or very good reduction does not always
      correlate with the functional outcome.

PMID- 17514181
TI  - Physical exercise in treatment of patients with lumbar discopathy.
AB  - BACKGROUND: The beneficial effect of physical exercise in the treatment of
      patients with intervertebral lumbar discopathy is generally known. Regular
      exercise has a beneficial effect on motor performance of the spine, increasing
      the degree of active stabilization. Exercise also improves posture control,
      coordination and precision of movement, preventing spinal fatigue and micro
      injuries. The purpose of our study was to evaluate the popularity of physical
      exercise in lumbar discopathy patients. MATERIAL AND METHODS: 665 patients, 16 76
      years of age, with L4-L5 or L5- with discopathy, were enrolled in the study.348
      patients received only conservative therapy, while 317 had undergone surgery.
      RESULTS: 55.6% of the conservatively managed patients and 57.4% of the surgically
      managed patients reported regular physical exercise. Patients receiving
      conservative therapy exercised for approx. 1 hour a week. Older patients
      exercised for a shorter period than young and middle-aged patients. In long-term
      follow-up, 2.2% more patients performed spinal exercises. Surgical patients
      devoted the most time to spinal exercise during the first 3 years after surgery.
      In long-term follow-up, the percentage of regularly exercising patients decreased
      by 3.9%. On average, 16.8% of conservatively managed patients and 21.5% of
      surgically managed patients exercised for more than 2 hours per week. Only
      approx. 20% of patients regularly engaged in spinal exercises for ca. 30 minutes
      daily. CONCLUSIONS: There is insufficient use of physical exercise of the spine
      for the prevention and treatment of lumbar discopathy.

PMID- 17514183
TI  - Prospective study to evaluate the efficacy of aripiprazole as a monotherapy in
      patients with severe chronic posttraumatic stress disorder: an open trial.
AB  - The objective of the study was to assess the efficacy and safety of aripiprazole
      in outpatients with posttraumatic stress disorder (PTSD) on a 12-week, open-label
      trial. Twenty-two subjects with DSM-IV diagnosis of PTSD participated; 16 were
      combat veterans. The primary outcome measure was PTSD symptom severity assessed
      with the Clinician Administered PTSD Scale (CAPS). Secondary outcome measures
      included the Positive and Negative Symptoms Scale and the Hamilton Depression and
      Anxiety Scales. All subjects had a CAPS score of > or = 60 at baseline. Lifetime
      history of psychotic disorders or bipolar illness was exclusionary. The overall
      analysis across time was Repeated Measures ANOVA, using Bonferroni corrections.
      Fourteen subjects completed 12 weeks of treatment. Eight subjects dropped-out due
      to side effects. For patients who discontinued, missing values were estimated
      using "the last observation carried forward" method. Significant improvements
      were seen on: CAPS total, all its subscales, positive symptoms, anxiety and
      depression scores. Fourteen participants were classified as responders, defined
      by 20% or greater improvement on CAPS total score. Of the 13 subjects who
      completed final ratings, CAPS total scores improved significantly (P = .011). Two
      subjects attained remission of PTSD (CAPS < 20), and three had a final CAPS < or
      = 26. The mean daily dose of aripiprazole was 12.95 mg. The most common side
      effects were somnolence (54.5%), restlessness (50%), insomnia (36.4%), and
      asthenia (31.8%). These results indicate that aripiprazole was effective in about
      two thirds of subjects that tolerated this medication. The initially high dropout
      rate may be related to intolerability due to a high starting dose (10 mg),
      suggesting beginning treatment at lower doses. These preliminary results are
      encouraging; a double blind study seems warranted.

PMID- 17514184
TI  - Awareness of metabolic concerns and perceived impact of pharmacotherapy in
      patients with bipolar disorder: a survey of 500 US psychiatrists.
AB  - OBJECTIVE: An online survey was conducted to assess psychiatrists' familiarity
      with the metabolic syndrome and its components in patients with bipolar disorder,
      and characterize their perspectives and practices regarding its impact on patient
      management. METHODS: Participants were US psychiatrists from a random sample of
      those in the AMA database. Qualified respondents practiced 4-30 years, spent > or
      = 50% of their time in direct patient care, and treated > or = 25 bipolar
      patients in the last month. Results were collected and tabulated by Harris
      Interactive from Nov-Dec 2005. RESULTS: Five hundred psychiatrists qualified and
      completed the survey, and 50 respondents also participated in follow-up
      interviews. Most respondents (94%) viewed metabolic syndrome as a significant
      health risk requiring monitoring and treatment. While 76% have diagnosed it, only
      28% correctly identified the five NCEP diagnostic criteria. Medication adverse
      effects of greatest concern were weight gain, glucose intolerance, and
      dyslipidemia. During treatment, 78% of respondents reported monitoring weight,
      69% glucose, 61% lipids, and 52% blood pressure. Most respondents (92%) reported
      referring patients to specialists or primary care for metabolic abnormalities.
      Changes in metabolic profile were reported to prompt many psychiatrists (85%) to
      stop or switch bipolar medications, especially those who treat a large number of
      bipolar patients (89%). The follow-up interviews supported a change in practice
      patterns over the last 5 years. CONCLUSIONS: Nearly all respondents have
      metabolic concerns with medical therapies used to treat bipolar disorder. Many
      now routinely monitor weight and other metabolic parameters. Most have referred
      patients for medical management and adjusted bipolar therapies due to metabolic
      abnormalities.

PMID- 17514185
TI  - Asenapine in the treatment of negative symptoms of schizophrenia: clinical trial
      design and rationale.
AB  - Although the positive symptoms of schizophrenia are more likely than the negative
      symptoms to result in a patient's hospitalization, positive symptoms tend to
      respond more completely to antipsychotic drugs.When positive symptoms are
      controlled, residual negative symptoms may remain. If these negative symptoms
      persist, they can have a considerable impact on a patient's ability to function
      in society. Current therapies have only a limited effect on negative symptoms.
      Consequently, broad-spectrum agents that effectively treat both positive and
      negative symptoms are needed. One obstacle to the regulatory approval of an agent
      for treating negative symptoms is the difficulty of designing a trial to
      demonstrate efficacy for these symptoms. Agreeing on a definition of negative
      symptoms, establishing patient inclusion criteria, and determining how to account
      for confounding factors represent only a few of the challenges to study design.
      How these challenges can be met is illustrated in the design of a series of
      clinical trials to assess the efficacy of asenapine, a psychopharmacologic agent
      being developed for the treatment of schizophrenia and, in particular, the
      treatment of negative symptoms associated with schizophrenia. These trials, the
      protocols for which are described in this paper, will not only determine the
      efficacy of asenapine but will add to our knowledge of patients with predominant,
      persistent negative symptoms, an understudied and inadequately treated patient
      population.

PMID- 17514186
TI  - Donepezil for cognitive decline following coronary artery bypass surgery: a pilot
      randomized controlled trial.
AB  - OBJECTIVE: To study the effect of donepezil in treating patients with cognitive
      decline following coronary artery bypass graft (CABG) surgery. METHODS: Forty
      four patients, with at least a 0.5 SD decline at 1 year post-CABG on at least one
      cognitive domain compared to their pre-CABG baseline score, were randomized to
      treatment with donepezil (titrated to 10 mg daily) or placebo in a 12-week double
      blind, single center, randomized study. A composite cognitive change score served
      as the primary outcome. Secondary outcome measures included tests of memory,
      attention, psychomotor speed, and executive function. RESULTS: The composite
      cognitive outcome did not show significant treatment effects. Secondary measures
      varied in their sensitivity to donepezil effects with the largest effects seen on
      the Wechsler Visual Memory Scale-Delayed and Immediate recall tests. More than
      twice (52% vs. 22%) as many donepezil-treated patients showed a significant
      improvement compared with placebo patients on Delayed recall. Tests with weak
      effect sizes and minimal trends favoring donepezil were the Boston Naming and
      Digit Symbol. However, most of the other instruments (e.g., Digit Span, Trails B,
      and Controlled Word Association) showed no treatment benefits. More donepezil
      treated than placebo-treated patients experienced diarrhea, but other adverse
      effects and safety measures did not differ between groups. CONCLUSION: In the
      post-CABG mild cognitive decline setting, donepezil did not improve composite
      cognitive performance but improved some aspects of memory. Donepezil was well
      tolerated and had no significant effects on EKG parameters. Because of
      limitations such as small sample size and multiplicity of tests, these findings
      are preliminary but add to our knowledge of cholinergic effects in vascular mild
      cognitive decline.

PMID- 17514187
TI  - The speed of onset of action of alprazolam-XR compared to alprazolam-CT in panic
      disorder.
AB  - This study compares the speed of onset of action of the extended release (XR)
      formulation of alprazolam with that of the compressed tablet (CT) formulation in
      a sample of outpatients with DSM-IV panic disorder. Diary records of hourly
      antianxiety benefit from a 9-week open label switch study of 30-patients
      stabilized on alprazolam- CT for 3 weeks and then switched to an equivalent dose
      of alprazolam-XR, were used to examine the timing and magnitude of clinical
      benefit on both formulations. The magnitude of benefit at the first hour after
      the first morning dose was similar for both formulations. The peak benefit, over
      the hours after the first morning dose, was also similar and 90% of peak benefit
      that was achieved in the first hour on both formulations. Mean time to peak
      benefit was similar (1.5 h for alprazolam-CT vs. 1.6 h for alprazolam-XR) and the
      percent of patients achieving peak benefit in the first hour was also similar.
      Compared to the CT formulation, alprazolam-XR had a much longer duration of
      therapeutic action (11.3 +/- 4.2 h vs. 5.1 +/- 1.7 h). The results, which may be
      related to the biotechnology (and resultant pharmacokinetic profile) of the XR
      preparation, suggest that alprazolam-XR has value as a "rescue" as well as a
      prophylactic or maintenance treatment in panic disorder. These results must be
      viewed in the context of the study limitations including its small size, the lack
      of independence of groups in a switch study, and the limitations of the diary
      records used.

PMID- 17514188
TI  - Long-acting injectable risperidone in the treatment of schizophrenia in special
      patient populations.
AB  - OBJECTIVE: Although atypical antipsychotic agents are effective in the treatment
      of schizophrenia, certain populations such as the elderly, young adults or those
      with a first episode of schizophrenia, and patients with schizoaffective disorder
      require special consideration when selecting pharmacotherapy. The introduction of
      a long-acting injectable atypical antipsychotic, long-acting risperidone, may be
      of benefit in these special groups. To determine the effectiveness of long-acting
      risperidone, the literature was reviewed to evaluate the efficacy and safety of
      long-acting risperidone in these populations. The impact of race was also
      considered. EXPERIMENTAL DESIGN: Studies published between January 2002 and
      November 2005 were reviewed as identified from literature searches using MEDLINE
      and Embase. The primary research parameter was "longacting risperidone" and
      literature pertaining to these particular patient groups selected. Abstracts and
      posters on long-acting risperidone presented at key psychiatry congresses were
      also reviewed during this time period. PRINCIPLE OBSERVATIONS: Results
      demonstrated that long-acting risperidone is effective and well tolerated in
      elderly patients, young patients or those with a first episode of schizophrenia,
      patients with schizoaffective disorder, and patients of different ethnicity. All
      patient groups demonstrated improvements in mean total Positive and Negative
      Syndrome Scale scores and Clinical Global Impressions of Severity Scale scores.
      Long-acting risperidone also reduced relapse rates and had a favourable
      tolerability profile. As such, long-acting risperidone has the potential to
      improve compliance in these vulnerable patient groups. CONCLUSIONS: Given the
      data presented here, further investigation of the effects of long-acting
      risperidone in these particular patient groups is warranted.

PMID- 17514189
TI  - Simple options for improving signal detection in antidepressant clinical trials.
AB  - OBJECTIVE: Previous experience with antidepressant studies highlight the
      difficulties in discriminating an effective drug from placebo. In hopes of
      improving signal detection, three easy-to-implement methodologies were employed
      during the development of a recently approved antidepressant. EXPERIMENTAL
      DESIGN: Results from alternative and traditional methods could be compared
      directly because most studies employed both methods. This database included 11
      double-blind, placebo-controlled trials (some with multiple dose arms and/or
      active comparators) yielding 22 treatment arms of antidepressants at or above the
      minimally effective dose noted in their U.S. labels. PRINCIPAL OBSERVATIONS:
      Results agreed with the previous evidence showing that the performance of a
      likelihood-based, mixed-effects model repeated measures (MMRM) analysis was
      superior to that of analysis of covariance with missing values imputed using the
      last observation carried forward (LOCF) approach; MMRM correctly identified drug
      as superior to placebo in 14/22 (63.6%) comparisons versus 11/22 (50.0%) for
      LOCF. In agreement with previous studies, use of subscales of the Hamilton
      Depression Rating scale (HAMD) improved signal detection compared to the HAMD
      total score. Using MMRM with HAMD subscales correctly identified drug as superior
      to placebo in up to 17/22 (77.3%) comparisons. Excluding double-blind, placebo
      lead-in responders did not increase the frequency of correctly identifying drug
      versus-placebo differences. CONCLUSIONS: The 22 drug-versus-placebo comparisons
      in this report offer a small amount of evidence and therefore may not be
      convincing on their own, although results do agree with previous research.
      Researchers may be able to take advantage of these easy-to-implement methods
      while we wait for further improvements in other areas.

PMID- 17514190
TI  - Searching for the puerperal trigger: molecular genetic studies of bipolar
      affective puerperal psychosis.
AB  - The available evidence suggests that the puerperium is a period of increased risk
      for acute episodes of illness in bipolar (BP) women and points to genetic factors
      as influencing vulnerability to postpartum triggering of such episodes. We have
      previously reported compelling evidence of familiarity of vulnerability to
      puerperal episodes in female sibs with BP disorder and find similar familial
      clustering for episodes of narrowly defined postpartum episodes in siblings with
      major depression. Molecular genetic approaches hold out the promise of uncovering
      the nature of the puerperal trigger leading to important improvements in the
      prevention and treatment of postpartum affective episodes. A research strategy
      focusing on positional and candidate gene approaches may prove fruitful in the
      search for susceptibility genes for both postpartum triggering in particular and
      for the affective disorder diathesis in general. We have identified the subset of
      families in the Wellcome Trust UK-Irish BP sib-pair molecular genetic linkage
      genome screen that include at least one female who has suffered an episode of
      puerperal psychosis. Analysis of this more homogeneous subgroup of families
      resulted in a genome-wide significant linkage signal (LOD = 4.07) on chromosome
      16p13 and genome wide suggestive linkage on chromosome 8q24. We are undertaking
      association studies in women with postpartum psychosis at a number of candidate
      genes of interest in BP disorder with an emphasis on those for which the
      expression is influenced by steroid hormones.

PMID- 17514191
TI  - Polypharmacy and EPS in a child; a case report.
AB  - Extrapyramidal symptoms (EPSs) (dystonic reaction, rigidity, and akathisia) occur
      as a result of D2 receptor blockade. Selective serotonin-reuptake inhibitors
      (SSRIs) have been reported to induce extrapyramidal signs and symptoms but
      tricyclic antidepressants have been rarely reported. Among the side effects
      attributed to valproic acid administration, the production of EPS is very rare,
      particularly in children. In this paper we present a case (10-year-old girl)
      under multiple pharmacologic treatment who developed EPSs (oculogyric crisis)
      shortly after the adjunct of imipramine to a combination of methylphenidate and
      valproic acid. Oculogyric crisis occurred on the third day of this combination
      treatment and these symptoms included ocular pain and sustained upward gaze.
      Benztropine 2 mg i.m. resulted in rapid relief of oculogyric crisis symptoms.

PMID- 17514192
TI  - Lithium-induced nephropathies.
AB  - Lithium, an alkali metal, remains the gold-standard of the pharmacological
      treatment of bipolar disorder. Over the past decades, the potential of lithium to
      cause renal damage has been an issue of debate. Polyuria, polydipsia, and, to a
      lesser degree, nephrogenic diabetes insipidus are frequently observed under
      treatment with lithium. The glomerular filtration rate (GFR) decreases
      progressively in a smaller proportion of subjects after several years of
      treatment with lithium. An even smaller number of patients continue to develop
      renal insufficiency, ultimately leading to hemodialysis in a small minority of
      subjects exposed to lithium. So far, no tests exist to identify subjects at risk
      of lithium-induced nephropathy at an early stage. Therefore, regular monitoring
      of creatinine and creatinine clearance are recommended in all subjects taking
      lithium.

PMID- 17514193
TI  - Antitumor effects of the MIG and IP-10 genes transferred with poly [D,L-2,4
      diaminobutyric acid] on murine neuroblastoma.
AB  - The number of tumor-infiltrating lymphocytes is known to be related to outcomes
      in patients with a variety of malignancies. Interferon (IFN) gamma-inducible
      protein-10 (IP-10) and monokine induced by IFNgamma (MIG) have chemotactic
      effects on activated T lymphocytes and natural killer (NK) cells. The aim of this
      study was to evaluate the antitumor effects of exogenous expression of the MIG
      and IP-10 genes delivered to solid tumors by poly [D,L-2,4-diaminobutyric acid]
      (PDBA). The murine MIG and IP-10 genes were transfected into mouse neuroblastoma
      cells with PDBA. MIG and IP-10 levels in supernatants of transfected cells were
      measured by enzyme-linked immunosorbent assay. The chemotactic activities of MIG
      and IP-10 in the supernatants of cell cultures were measured by chemotaxis assay.
      Tumors were injected in vivo with PDBA/pmMIGColon, two colonsIP-10 complexes to
      evaluate the effects of these genes on tumor volume and survival time of mice.
      Transfected PDBA/pmMIGColon, two colonsIP-10 complexes produced MIG and IP-10
      protein in vitro. MIG and IP-10 proteins secreted into the culture medium showed
      chemotactic activity. MIG and IP-10 gene therapy with the PDBA system in vivo
      significantly inhibited tumor growth and prolonged survival time of mice. In
      conclusion, PDBA-mediated MIG and IP-10 gene therapy may be useful for treatment
      of solid tumors.

PMID- 17514194
TI  - 10-year follow-up of gene-modified adenoviral-based therapy in 146 non-small-cell
      lung cancer patients.

PMID- 17514195
TI  - NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders.
AB  - The number and subunit composition of synaptic N-methyl-D-aspartate receptors
      (NMDARs) are not static, but change in a cell- and synapse-specific manner during
      development and in response to neuronal activity and sensory experience. Neuronal
      activity drives not only NMDAR synaptic targeting and incorporation, but also
      receptor retrieval, differential sorting into the endosomal-lysosomal pathway and
      lateral diffusion between synaptic and extrasynaptic sites. An emerging concept
      is that activity-dependent, bidirectional regulation of NMDAR trafficking
      provides a dynamic and potentially powerful mechanism for the regulation of
      synaptic efficacy and remodelling, which, if dysregulated, can contribute to
      neuropsychiatric disorders such as cocaine addiction, Alzheimer's disease and
      schizophrenia.

PMID- 17514196
TI  - Neuronal subtype specification in the cerebral cortex.
AB  - In recent years, tremendous progress has been made in understanding the
      mechanisms underlying the specification of projection neurons within the
      mammalian neocortex. New experimental approaches have made it possible to
      identify progenitors and study the lineage relationships of different neocortical
      projection neurons. An expanding set of genes with layer and neuronal subtype
      specificity have been identified within the neocortex, and their function during
      projection neuron development is starting to be elucidated. Here, we assess
      recent data regarding the nature of neocortical progenitors, review the roles of
      individual genes in projection neuron specification and discuss the implications
      for progenitor plasticity.

PMID- 17514197
TI  - Cell-cycle control and cortical development.
AB  - The spatio-temporal timing of the last round of mitosis, followed by the
      migration of neuroblasts to the cortical plate leads to the formation of the six
      layered cortex that is subdivided into functionally defined cortical areas.
      Whereas many of the cellular and molecular mechanisms have been established in
      rodents, there are a number of unique features that require further elucidation
      in primates. Recent findings both in rodents and in primates indicate that
      regulation of the cell cycle, specifically of the G1 phase has a crucial role in
      controlling area-specific rates of neuron production and the generation of
      cytoarchitectonic maps.

PMID- 17514198
TI  - The action potential in mammalian central neurons.
AB  - The action potential of the squid giant axon is formed by just two voltage
      dependent conductances in the cell membrane, yet mammalian central neurons
      typically express more than a dozen different types of voltage-dependent ion
      channels. This rich repertoire of channels allows neurons to encode information
      by generating action potentials with a wide range of shapes, frequencies and
      patterns. Recent work offers an increasingly detailed understanding of how the
      expression of particular channel types underlies the remarkably diverse firing
      behaviour of various types of neurons.

PMID- 17514199
TI  - Enteric nervous system development and Hirschsprung's disease: advances in
      genetic and stem cell studies.
AB  - The enteric nervous system (ENS) has been explored by developmental
      neurobiologists and medical researchers for decades. Whereas developmental
      biologists have been unravelling the molecular mechanisms underlying the
      migration, proliferation and differentiation of the neural crest derivatives that
      give rise to the ENS, human geneticists have been uncovering the genetic basis
      for diseases of the ENS, notably Hirschsprung's disease. Here we discuss the
      exciting recent advances, including novel transgenic and genetic tools, a
      broadening range of model organisms, and the pursuit of ENS stem cells as a
      therapeutic tool, that are bringing these fields closer together.

PMID- 17514200
TI  - How widespread is adult neurogenesis in mammals?
AB  - It is now widely accepted that neurogenesis occurs in two regions of the adult
      mammalian brain--the hippocampus and the olfactory bulb. There is evidence for
      adult neurogenesis in several additional areas, including the neocortex,
      striatum, amygdala and substantia nigra, but this has been difficult to replicate
      consistently other than in the damaged brain. The discrepancies may be due to
      variations in the sensitivity of the methods used to detect new neurons.

PMID- 17514201
TI  - Reviewing appeals.

PMID- 17514202
TI  - Antifungal defense in Drosophila.

PMID- 17514203
TI  - Why study the evolution of immunity?

PMID- 17514204
TI  - Antifungal defense turns 17.

PMID- 17514205
TI  - DNA deaminases converge on adaptive immunity.

PMID- 17514206
TI  - All roads lead to CARD9.

PMID- 17514207
TI  - DC-SIGN 'AIDS' HIV immune evasion and infection.

PMID- 17514208
TI  - The origin of dendritic cells.

PMID- 17514210
TI  - Patterns of nonclassical MHC antigen presentation.
AB  - The identification of pattern-recognition receptors that selectively respond to
      evolutionarily conserved chemical (often pathogen-derived) moieties has provided
      key insight into how innate immune cells facilitate rapid and relatively specific
      antimicrobial immune activity. In contrast, relatively slower adaptive immune
      responses rely on T cell clonal expansion that develops in response to variable
      peptides bound to the groove of classical major histocompatibility complex (MHC)
      proteins. For certain nonclassical 'MHC-like' class Ib proteins, such as H2-M3
      and CD1d, their respective binding grooves seem to have been adapted to present
      to T cells unique molecular patterns analogous to those involved in innate
      signaling. Here we propose that another MHC class Ib protein, MR1, which is
      required for the gut flora-dependent development of mucosa-associated invariant T
      cells, presents either a microbe-produced or a microbe-induced pattern.

PMID- 17514211
TI  - Issues in implementing a real competency-based training and assessment system.
AB  - "First, do no harm" is a medical admonition; but harm does occur. There is thus
      mounting pressure for Medicine to adopt more rigorous systems to ensure
      professional competency. Traditionally, medical education and professional
      development has focussed on developing clinical expertise and technical skills
      within each speciality. Recent studies into the causes of adverse events have
      highlighted that the failure of non-technical aspects of competency are more
      common than the failure of technical skills amongst health professionals.
      Traditional training has also focussed on the individual and yet error management
      strategies in organisations that require high reliability processes for
      maintaining safe practice puts the emphasis on the team. It is our contention
      that the delivery of safe patient care requires a redefinition of professional
      competency--in terms of the interface between members of the team, patients and
      the organisational and social requirements of the health system. A change to
      competency-based training and assessment will require a team-orientated
      definition of professional competency that may challenge individual professionals
      and the sovereignty of medical specialities.

PMID- 17514212
TI  - Get the learning environment right and the facts will look after themselves.

PMID- 17514213
TI  - Efficacy of steroids in preventing cutaneous heparin-related allergic reactions
      in patients requiring anticoagulation.

PMID- 17514214
TI  - Medical image. Advanced oesophageal cancer complicated with tracheoesophageal
      fistula and aspiration pneumonia.

PMID- 17514215
TI  - Profound hypokalaemia secondary to a large rectosigmoid villous tumour.

PMID- 17514216
TI  - Procedural and examination skills of first-year postgraduate doctors do not
      improve with clinical experience alone.
AB  - AIM: To look for factors mitigating for or against first-year postgraduate house
      surgeons (PGY1) gaining experience in examination and procedural skills. METHODS:
      Ten PGY1s at Hutt Hospital (Lower Hutt, New Zealand) filled in self-reporting
      questionnaires to assess the impact of 6 months of on-the-ward training on their
      baseline competence in clinical examination and procedural skills. Opportunities
      for skills acquisition, and barriers (if any) towards gaining experience were
      assessed. RESULTS: The small numbers of PGY1s limit generalisation of the
      findings, however certain trends are evident. Improvements were seen in commonly
      carried out procedures, though gaps in these areas could still be present after 6
      months. Commonly performed examinations such as auscultation of heart sounds and
      murmurs improved, though in the area of intimate exams and fundoscopy there was
      little confidence gained. Log diaries show that opportunities for practice of
      clinical procedures were limited and that regular weekly practice only occurred
      with arterial blood gases and intravenous (IV) cannulation. A discussion group
      analysis revealed that competition with other PGY1s for the limited number of
      opportunities and the random occurrence of practical procedures were barriers to
      gaining skills. CONCLUSIONS: Clinical on-the-ward experience is not always enough
      to gain clinical skills and perhaps alternate means such as simulation need to be
      explored.

PMID- 17514217
TI  - Procedural and examination skills of first-year house surgeons: a comparison of a
      simulation workshop versus 6 months of clinical ward experience alone.
AB  - AIM: To assess the impact of a simulation workshop prior to starting clinical
      work, on the practical and examination skills of first-year postgraduate house
      surgeons (PGY1s) starting at Hutt Hospital (Lower Hutt, New Zealand) and to
      compare this to 6 months of clinical ward experience alone. METHODS: Self
      reporting questionnaires on clinical examination, and procedural skills were used
      to compare a 'control' group of 10 PGY1s who had 6 months on-the-ward training
      only, to a second 'intervention' group of 10 PGY1s who underwent training in a
      simulation skills workshop prior to starting clinical work. RESULTS: The small
      numbers of PGY1s limit generalisation of the findings, however certain trends are
      evident. The skills workshop improved self-rated competence scores in clinical
      procedural skills, and was significant for lumbar punctures (LP) and spirometry.
      Scores were comparable to those of 6 months of clinical exposure alone. Self
      reported confidence scores in picking up abnormalities of clinical examination
      improved in all areas taught and were significant for fundal, prostate, and
      rectal abnormalities. Scores exceeded those achieved with 6 months of clinical
      exposure. CONCLUSIONS: The findings suggest that a skills workshop prior to
      starting clinical work may approximate 6 months of clinical experience and
      improve baseline procedural and examination skills.

PMID- 17514218
TI  - How many health professionals does a patient see during an average hospital stay?
AB  - AIM: To assess how many health professionals are directly involved in a patient's
      stay at Auckland City Hospital, Auckland, New Zealand. METHODS: A retrospective
      review of the records was carried out of all patients admitted through the
      Admission and Planning Unit and the Emergency Department on a chosen day. Every
      health professional who wrote in the medical notes was counted and tabulated for
      each patient. RESULTS: 81 patients were admitted--47 medical and 34 surgical. In
      medicine, the patients saw an average of 17.8 health professionals during their
      hospitalisation (95%CI 0.0-36.7) (median 17) (range 5 to 44); an average of 6.0
      doctors (0.0-12.6) (5) (2-21); 10.7 nurses (0.0-22.3) (11) (3-24); and 1.0 allied
      health workers (0.0-4.5) (0) (0-6). In surgery, the patients saw an average of
      26.6 health professionals during their hospitalisation (95%CI 0.0-66.7) (median
      21.5) (range 2 to 75); an average of 10.0 doctors (0.0-25.8) (8.5) (1-33); 15.9
      nurses (0.0-39.2) (13.5) (1-44); and 0.8 allied health workers (0-3.3) (0) (0-4).
      CONCLUSIONS: Modern hospital healthcare delivery involves many different
      healthcare professionals. Patients have more nurse contacts than doctors
      (p<0.0001). Surgical patients see more health professionals than medical patients
      overall (p=0.01) but the daily rate was not found to be statistically different
      (p=0.3). Involvement of different health professionals may necessitate good
      communication/handover processes as well as possible changes to traditional
      training methods.

PMID- 17514219
TI  - For better or worse: role models for New Zealand house officers.
AB  - Role modelling is considered an important influence on emerging professional
      identity. However as a process it goes largely uninspected. In an effort to
      develop greater awareness of this important process, this study examines the
      positive and negative role modelling experiences of New Zealand house officers.

PMID- 17514220
TI  - Doctors, practices, patients, and their problems during usual hours: a
      description of rural and non-rural primary care in New Zealand in 2001-2002.
AB  - AIM: To describe the characteristics of patients who attended rural general
      practice offices in New Zealand in 2001/2 during normal hours along with the
      problems they presented and the management that they received. Comparisons are
      made with patients who attended non-rural practices. METHODS: Data were collected
      from a stratified random survey of GPs in New Zealand as part of the National
      Primary Medical Care survey carried out in 2001/2. RESULTS: Response rates at
      rural and non-rural general practices were high (72%). Comparing practice
      characteristics by locale, there were fewer full-time equivalent doctors in rural
      settings, their practice fees were lower, their throughput was slightly higher,
      and more services were provided (such as evening surgery, group health promotion
      and doctors involved in maternity care). More rural practitioners had graduated
      overseas than their urban counterparts but their characteristics were otherwise
      similar. Patients who presented to rural practices were similar in age and
      gender, but a higher proportion were M?ori and more were from more deprived
      areas. Patients made a similar number of visits as people in non-rural areas,
      although visits were slightly shorter in rural practices and more were funded by
      Accident Compensation Corporation (ACC). Rural patients presented slightly fewer
      reasons or problems per visit. Injury and respiratory conditions were more
      frequent problems managed at rural practices. Patient management was generally
      similar regardless of location, although laboratory tests and other
      investigations were ordered less frequently at rural practices. Prescriptions and
      non-drug treatments were also provided slightly less often at rural practices and
      follow-up was arranged less frequently. CONCLUSIONS: Aside from a few key
      differences, the characteristics of patients, practitioners, and practice were
      generally similar between rural and non-rural locations during normal hours in
      2001/2. With some notable exceptions, patient problems and their management were
      also broadly consistent. Further work is needed to develop an ongoing database of
      patient morbidity encountered in primary care, ideally with more information
      about the complexity of each encounter and the nature of after-hours work.

PMID- 17514221
TI  - Taxation of New Zealand doctors.

PMID- 17514222
TI  - Burns treatment in New Zealand: another response to Patricia Holborow's letter on
      saline baths for burns patients.

PMID- 17514224
TI  - Scene-based method for spatial misregistration detection in hyperspectral
      imagery.
AB  - Hyperspectral imaging (HSI) sensors suffer from spatial misregistration, an
      artifact that prevents the accurate acquisition of the spectra. Physical
      considerations let us assume that the influence of the spatial misregistration on
      the acquired data depends both on the wavelength and on the across-track
      position. A scene-based method, based on edge detection, is therefore proposed.
      Such a procedure measures the variation on the spatial location of an edge
      between its various monochromatic projections, giving an estimation for spatial
      misregistration, and also allowing identification of misalignments. The method
      has been applied to several hyperspectral sensors, either prism, or grating-based
      designs. The results confirm the dependence assumptions on lambda and theta,
      spectral wavelength and across-track pixel, respectively. Suggestions are also
      given to correct for spatial misregistration.

PMID- 17514225
TI  - Segmented chirped grating for coarse wavelength division demultiplexing with
      multimode optical fibers.
AB  - A chirped grating segmented into partitions each having a constant blaze angle to
      use in a demultiplexer for coarse wavelength division multiplexing with multimode
      optical fibers is developed. Its designed configuration utilizes a resonance
      region to achieve high diffraction efficiency and large dispersion. The width,
      blaze angle, and diffraction order of each partition were optimized by vector
      diffraction analysis. The diffraction loss of the manufactured grating was less
      than 1.5 dB, and polarization-dependent loss was less than 0.6 dB within a
      wavelength width of at least 70 nm. It is confirmed that a demultiplexer with the
      developed chirped grating had a wide passband and low cross talk.

PMID- 17514226
TI  - Design and investigation of color separation diffraction gratings.
AB  - Color separation gratings (CSGs) are designed within the framework of the
      rigorous electromagnetic theory using a gradient method. The optimality of the
      scalar-theory-based solutions is estimated. The results of the experimental study
      of a CSG to separate three wavelengths are presented.

PMID- 17514227
TI  - Influence of surrounding media refractive index on the thermal and strain
      sensitivities of long-period gratings.
AB  - A detailed study of the thermal and strain sensitivities of a long-period grating
      when the device is immersed in different external media is presented. The range
      of refractive indices analyzed are within 1.000 to 1.447, corresponding to
      samples of air, water, ethanol, naphtha, thinner, turpentine, and kerosene.
      Within the same range of refractive indices, the strain sensitivity is between (
      0.24 +/- 0.03) and (-0.94 +/- 0.11) pm/microepsilon. For the grating immersed in
      these fluids, the refractive index sensitivity ranges from -3 to -1035.6 nm per
      refractive index units. The coupling thermo-optic coefficients and the strain
      optic coefficients are also measured, resulting in the range from (2.45 +/-
      0.04)x10(-5) to (15.89 +/- 0.82)x10(-5) deg C(-1) and (-1.15 +/- 0.04) to (-1.61
      +/- 0.04) microepsilon(-1), respectively. A noticeable nonlinear behavior of the
      thermal sensitivity is found for external media with refractive indices higher
      than 1.430.

PMID- 17514228
TI  - Non-laser-based scanner for three-dimensional digitization of historical
      artifacts.
AB  - A 3D scanner, based on incoherent illumination techniques, and associated data
      processing algorithms are presented that can be used to scan objects at lateral
      resolutions ranging from 5 to 100 microm (or more) and depth resolutions of
      approximately 2 microm. The scanner was designed with the specific intent to scan
      cuneiform tablets but can be utilized for other applications. Photometric stereo
      techniques are used to obtain both a surface normal map and a parameterized model
      of the object's bidirectional reflectance distribution function. The normal map
      is combined with height information, gathered by structured light techniques, to
      form a consistent 3D surface. Data from Lambertian and specularly diffuse
      spherical objects are presented and used to quantify the accuracy of the
      techniques. Scans of a cuneiform tablet are also presented. All presented data
      are at a lateral resolution of 26.8 microm as this is approximately the minimum
      resolution deemed necessary to accurately represent cuneiform.

PMID- 17514229
TI  - Uncertainty evaluation for the spectroradiometric measurement of the averaged
      light-emitting diode intensity.
AB  - An uncertainty evaluation is presented for the spectroradiometric measurement of
      the averaged LED intensity (ALI), which is a standardized photometric quantity of
      LEDs introduced by the Commission Internationale de l'Eclairage. Using a spectral
      irradiance standard lamp as a calibration source for the spectroradiometer, 12
      uncertainty components are sorted out and their propagation formulated with
      correlations between the components taken into account. The procedure of
      uncertainty evaluation is demonstrated for four LED samples of different colors;
      red, green, blue, and white. The relative uncertainties of the ALI of the test
      samples are determined to be in a range from 4.1% to 5.5% (k=2), but most of
      their dominant uncertainty components turn out to be systematic and correlated.
      In conclusion, correlations between the uncertainty components critically affect
      the overall uncertainty of the LED measurement using a spectroradiometer.

PMID- 17514230
TI  - Evaluation of two-dimensional displacement components of symmetrical deformation
      by phase-shifting electronic speckle pattern interferometry.
AB  - A method for the isolation of two-dimensional (2D) displacement components by
      using one phase map obtained by phase-shifting electronic speckle pattern
      interferometry (ESPI) is presented. When the typical ESPI is used for
      displacement measurement, a mixed phase distribution of deformation is measured.
      If the deformation of the object is symmetrical, two components of deformation
      can be separated from each other by using the mixed phase distribution. We turn
      over the mixed phase map first to obtain the second phase map, and then overlap
      them. Two displacement components can be separated from each other by boundary
      alignment and algebraic calculation between the two phase maps. This method has
      been proved feasible by a typical three-point bending experiment. Some
      experimental results are offered and compared with the results obtained by a dual
      beam symmetrical illuminations experiment. This technique presented provides an
      alternative approach to 2D deformation measurement.

PMID- 17514231
TI  - Measuring the thickness profiles of wafers to subnanometer resolution using Fabry
      Perot interferometry.
AB  - The resolution of an angle-scanning technique for measuring transparent optical
      wafers is analyzed, and it is shown both theoretically and experimentally that
      subnanometer resolution can be readily achieved. Data are acquired simultaneously
      over the whole area of the wafer, producing two-dimensional thickness variation
      maps in as little as 10 s. Repeatabilities of 0.07 nm have been demonstrated, and
      wafers of up to 100 mm diameter have been measured, with 1 mm or better spatial
      resolution. A technique for compensating wafer and system aberrations is
      incorporated and analyzed.

PMID- 17514232
TI  - Thermodynamic-temperature determinations of the Ag and Au freezing temperatures
      using a detector-based radiation thermometer.
AB  - The development of a radiation thermometer calibrated for spectral radiance
      responsivity using cryogenic, electrical-substitution radiometry to determine the
      thermodynamic temperatures of the Ag- and Au-freezing temperatures is described.
      The absolute spectral radiance responsivity of the radiation thermometer is
      measured in the NIST Spectral Irradiance and Radiance Responsivity Calibrations
      using Uniform Sources (SIRCUS) facility with a total uncertainty of 0.15% (k=2)
      and is traceable to the electrical watt, and thus the thermodynamic temperature
      of any blackbody can be determined by using Planck radiation law and the measured
      optical power. The thermodynamic temperatures of the Ag- and Au-freezing
      temperatures are determined to be 1234.956 K (+/-0.110 K) (k=2) and 1337.344 K(+/
      0.129 K) (k=2) differing from the International Temperature Scale of 1990 (ITS
      90) assignments by 26 mK and 14 mK, respectively, within the stated
      uncertainties. The temperatures were systematically corrected for the size- of
      source effect, the nonlinearity of the preamplifier and the emissivity of the
      blackbody. The ultimate goal of these thermodynamic temperature measurements is
      to disseminate temperature scales with lower uncertainties than those of the ITS
      90. These results indicate that direct disseminations of thermodynamic
      temperature scales are possible.

PMID- 17514233
TI  - Development of a multi-Fourier-transform interferometer: imaging experiments in
      millimeter and submillimeter wave bands.
AB  - We have developed a millimeter and submillimeter Michelson-type bolometric
      interferometer based on a Martin-Puplett-type Fourier-transform spectrometer
      named multi-Fourier-transform interferometer (MuFT). We have succeeded in proving
      that the MuFT is capable of performing broadband imaging observations as
      theoretically proposed by our previous paper (OHM) [Appl. Opt. 45, 2576 (2006)].
      We succeeded in acquiring the mutual coherence signal for an extended source in
      broadband. By analyzing the obtained mutual coherence signal following the
      formula proposed in OHM, 2D source images for each wavenumber from 5 cm(-1) (150
      GHz) to 35 cm(-1) (1.05 THz) with a wavenumber interval of 0.4 cm(-1) (12 GHz)
      were successfully extracted. The large dynamic range advantage of the MuFT
      proposed in OHM was confirmed experimentally.

PMID- 17514234
TI  - Interferometric optical vortex array generator.
AB  - Two new interferometric configurations for optical vortex array generation are
      presented. These interferometers are different from the conventional
      interferometers in that they are capable of producing a large number of isolated
      zeros of intensity, and all of them contain optical vortices. Simulation and
      theory for optical vortex array generation using three-plane-wave interference is
      presented. The vortex dipole array produced this way is noninteracting, as there
      are no attraction or repulsion forces between them, leading to annihilation or
      creation of vortex pairs.

PMID- 17514235
TI  - Design and fabrication of a novel reflection filter.
AB  - Reflection filters are useful in optical communication, display, and other
      systems. A novel reflection filter is designed and fabricated. Analytical design
      formulas have been put forward and show good agreement with the measured maximum
      reflectance as well as with the bandwidth at the central wavelength. The
      effective admittance and distribution of the electrical field intensity are also
      calculated to analyze the properties of the filter. This novel filter with high
      peak reflectance, narrow bandwidth, and deep cutoff, is simple to design, easy to
      fabricate and convenient to integrate, compared with the conventional dielectric
      multilayer reflection filters.

PMID- 17514236
TI  - Integral merit function for broadband omnidirectional mirrors.
AB  - By using the notion of wavelength- and angle-averaged reflectance, we assess in a
      systematic way the performance of finite omnidirectional reflectors. We put
      forward how this concept can be employed to optimize omnidirectional
      capabilities. We also apply it to give an alternative meaningful characterization
      of the bandwidth of these systems.

PMID- 17514237
TI  - Tangent least-squares fitting filtering method for electrical speckle pattern
      interferometry phase fringe patterns.
AB  - An efficient method is proposed to reduce the noise from electrical speckle
      pattern interferometry (ESPI) phase fringe patterns obtained by any technique. We
      establish the filtering windows along the tangent direction of phase fringe
      patterns. The x and y coordinates of each point in the established filtering
      windows are defined as the sine and cosine of the half-wrapped phase multiplied
      by a random quantity, then phase value is calculated using these points'
      coordinates based on a least-squares fitting algorithm. We tested the proposed
      methods on the computer-simulated speckle phase fringe patterns and the
      experimentally obtained phase fringe pattern, respectively, and compared them
      with the improved sine/cosine average filtering method [Opt. Commun. 162, 205
      (1999)] and the least-squares phase-fitting method [Opt. Lett. 20, 931 (1995)],
      which may be the most efficient methods. In all cases, our results are even
      better than the ones obtained with the two methods. Our method can overcome the
      main disadvantages encountered by the two methods.

PMID- 17514238
TI  - Invariants of polarization transformations.
AB  - The use of polarization-sensitive sensors is being explored in a variety of
      applications. Polarization diversity has been shown to improve the performance of
      the automatic target detection and recognition in a significant way. However, it
      also brings out the problems associated with processing and storing more data and
      the problem of polarization distortion during transmission. We present a
      technique for extracting attributes that are invariant under polarization
      transformations. The polarimetric signatures are represented in terms of the
      components of the Stokes vectors. Invariant algebra is then used to extract a set
      of signature-related attributes that are invariant under linear transformation of
      the Stokes vectors. Experimental results using polarimetric infrared signatures
      of a number of manmade and natural objects undergoing systematic linear
      transformations support the invariancy of these attributes.

PMID- 17514239
TI  - Atmospheric aerosol profiling with a bistatic imaging lidar system.
AB  - Atmospheric aerosols have been profiled using a simple, imaging, bistatic lidar
      system. A vertical laser beam is imaged onto a charge-coupled-device camera from
      the ground to the zenith with a wide-angle lens (CLidar). The altitudes are
      derived geometrically from the position of the camera and laser with submeter
      resolution near the ground. The system requires no overlap correction needed in
      monostatic lidar systems and needs a much smaller dynamic range. Nighttime
      measurements of both molecular and aerosol scattering were made at Mauna Loa
      Observatory. The CLidar aerosol total scatter compares very well with a
      nephelometer measuring at 10 m above the ground. The results build on earlier
      work that compared purely molecular scattered light to theory, and detail
      instrument improvements.

PMID- 17514240
TI  - Modeling the reflection of a laser beam by a deformed highly reflective volume
      bragg grating.
AB  - A model is presented for analyzing volume Bragg gratings having large diffractive
      strength that may become distorted upon the passage of high-power laser light.
      One result of this analysis is that very little distortion in a volume Bragg
      grating can greatly reduce the reflectivity. This is a critical issue in the
      design of systems in which these devices are used to combine high-power laser
      beams.

PMID- 17514241
TI  - Wavelength division multiplexing addressed four-element fiber optical laser
      hydrophone array.
AB  - A four-element hydrophone array system using a fiber Bragg grating laser system
      is described. The demodulation technique for the array combines a 3x3 coupler
      based interferometer and three wavelength division multiplexers (WDMs). It is
      believed to be a new passive approach to use a WDM and a unique arithmetic
      method. The operational frequency limit depends only on the frequency of its
      electronic portion. The designed system has achieved a minimum of approximately
      7.2x10(-7) pm/ radicalHz detectable wavelength perturbation for frequencies that
      are greater than 200 Hz.

PMID- 17514242
TI  - Tightly focused epimicroscope technique for submicrometer-resolved highly
      sensitive refractive index measurement of an optical waveguide.
AB  - We introduce a very sensitive new configuration, to the best of our knowledge, in
      an optical microscope system that utilizes two detectors: one is to measure the
      power of a low reflected signal from a sample, and the other is only to monitor
      the confocal geometry of the system. With this new configuration, we could
      effectively remove measurement noise associated with small perturbation in
      measurement conditions such as surface curvature, tilt, and vibration in a
      microscope system. We have obtained a high-resolution relative index precision of
      9x10(-5) by employing this novel technique with two detectors.

PMID- 17514243
TI  - Miniature rainbow schlieren deflectometry system for quantitative measurements in
      microjets and flames.
AB  - Recent interest in small-scale flow devices has created the need for miniature
      instruments capable of measuring scalar flow properties with high spatial
      resolution. We present a miniature rainbow schlieren deflectometry system to
      nonintrusively obtain quantitative species concentration and temperature data
      across the whole field. The optical layout of the miniature system is similar to
      that of a macroscale system, although the field of view is smaller by an order of
      magnitude. Employing achromatic lenses and a CCD array together with a camera
      lens and extension tubes, we achieved spatial resolution down to 4 mum.
      Quantitative measurements required a careful evaluation of the optical
      components. The capability of the system is demonstrated by obtaining
      concentration measurements in a helium microjet (diameter, d=650 microm) and
      temperature and concentration measurements in a hydrogen jet diffusion flame from
      a microinjector (d=50 microm). Further, the flow field of underexpanded nitrogen
      jets is visualized to reveal details of the shock structures existing downstream
      of the jet exit.

PMID- 17514244
TI  - Shack-Hartmann wavefront sensor measurement for dynamic temperature profiles in
      heat-capacity laser rods.
AB  - A Shack-Hartmann sensor nonintrusive measurement for the temperature profile in a
      heat-capacity neodymium-doped glass rod is proposed. This technique is possible
      because the optical path length of the rod changes with temperature linearly over
      a wide range. The temperature change of the solid-state laser rod is often
      recorded by using a thermocouple, thermal camera, or phase-shifting
      interferometer. Based on an analysis of temperature-induced changes in length and
      index of refraction, we can get the temperature profiles from the wavefront
      reconstructions in real time. The results suggest the Shack-Hartmann sensors
      could replace microbolometer-based thermal cameras and phase-shifting
      interferometers for dynamic temperature profiles in heat-capacity laser rods with
      particular advantages. A strange temperature chaos of the Nd:glass rod just after
      the pump cycle is discovered.

PMID- 17514245
TI  - Resonance spectrum of a three-dimensional photonic quantum ring laser with an
      equilateral triangle microcavity.
AB  - We have fabricated three-dimensional (3D) photonic quantum ring lasers with an
      equilateral triangle microcavity. Their spectra were well explained by combining
      the off-normal resonance and hexagonally bounced in-plane whispering-gallery-mode
      condition. The angular distribution of the emission modes and their discrete
      wavelengths were shown to be in excellent agreement with a 3D Rayleigh Fabry
      Perot model. We confirmed that the allowed modes in the equilateral triangle
      microcavity decrease by decreasing the length of equilateral triangle side, L,
      and the spectral mode spacing linearly increases with the mode index m and is
      inversely proportional to L2.

PMID- 17514246
TI  - High-power high-repetition-rate UV light at 355 nm generated by a diode-end
      pumped passively Q-switched Nd:YAG laser.
AB  - We describe experimental results with a diode-pumped, passively Q-switched
      extracavity second- and third-harmonic generation. Cr:YAG is used as a saturable
      absorber for pulse generation. Taking into account the thermal effects of Nd:YAG
      at high incident pump power, we use a short plane-to-plane cavity configuration
      to take advantage of the maximum pump power and obtain the compactness structure.
      At the same time, we use the type-I critical phase-matched lithium triborate
      crystal to generate light at 532 nm and mix the residual fundamental at 1064 nm
      and the second-harmonic wave at 532 nm in the type-II critical phase-matched
      lithium triborate crystal for UV light generation at 355 nm. A third-harmonic
      generation output power of 1.32 W is achieved at the incident pump power of 27.5
      W, corresponding to an optical-to-optical efficiency of 4.8%. The instability of
      the UV laser power is less than 5% for 4 h.

PMID- 17514247
TI  - Nonplanar ring resonator modes: generalized Gaussian beams.
AB  - Several findings on the modes of a nonplanar ring resonator have been carried out
      by utilizing the matrix method of generalized Gaussian beams. The widely used
      nonplanar ring resonator--a four-equal-sided nonplanar ring cavity with two
      curvature mirrors and two planar mirrors--has been chosen as an example. The
      overall stability maps of this typical nonplanar ring cavity with L/R ranging
      from 0 to infinity are calculated and described, while the total cavity length is
      L and the radius of the curvature mirrors is R. The stability map has also been
      found to have asymmetry with total image rotation rho ranging from 0 degrees to
      360 degrees and 0<L/R<2. It has also been found that there still exist several
      stable regions in the extended region with L/R>2. The Gaussian modes of the
      nonplanar ring cavity have been found to have different characteristics with
      different design parameters such as rho and L/R. The azimuth angles of the major
      and minor axes of the spot size have been found to be variable with different
      design parameters such as rho and L/R and variable under different location of
      the nonplanar cavity. These interesting findings are totally different from the
      behavior of conventional planar stable resonators and are important to the cavity
      designs of nonplanar ring resonators.

PMID- 17514248
TI  - Raman shifter optimized for lidar at a 1.5 microm wavelength.
AB  - A Raman shifter is optimized for generating high-energy laser pulses at a 1.54
      microm wavelength. A forward-scattering design is described, including details of
      the multiple pass and nonfocused optical design, Stokes injection seeding, and
      internal gas recirculation. First-Stokes conversion efficiencies up to 43%-
      equivalent to 62% photon conversion efficiency--were measured. Experimental
      results show output average power in excess of 17.5 W, pulse energies of 350 mJ
      at 50 Hz, with good beam quality (M2<6). Narrow bandwidth and tunable output is
      produced when pumping with a single longitudinal mode Nd:YAG laser and seeding
      the process with a Stokes wavelength narrowband laser diode.

PMID- 17514249
TI  - Improved amplified spontaneous emission by doping of green fluorescent dye C545T
      in red fluorescent dye DCJTB:PS polymer films.
AB  - Amplified spontaneous emission (ASE) characteristics of a red fluorescent dye, 4
      (dicy-anomethylene)-2-t-butyl-6(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran
      (DCJTB), and a green fluorescent dye, (10-(2-benzothiazolyl)-1,1,7,7-tetramethyl
      2,3,6,7-tetrahydro-1H,5H,11H-[1] benzopyrano [6,7,8-ij]quinolizin-11-one) (C545T)
      codoped polystyrene (PS) as the active medium were studied. It was found that the
      performance of ASE is greatly improved due to the introduction of C545T. By
      optimizing the concentrations of C545T and DCJTB in PS, an ASE threshold of 0.016
      mJ pulse(-1), net gain of 52.71 cm(-1), and loss of 11.7 cm(-1) were obtained.
      The efficient Forster energy transfer from C545T to DCJTB was used to explain the
      improvement of the ASE performance in the coguest system.

PMID- 17514250
TI  - Efficient generation of a three-primary-color laser from the second-harmonic
      emission of a Nd:YAG laser.
AB  - Laser emission, consisting of three primary colors, is generated by frequency
      conversions of the second-harmonic emission of a picosecond (120 ps) Nd:YAG laser
      by means of stimulated Raman scattering and subsequent four-wave Raman mixing in
      molecular deuterium. In the double-pass configuration, the fundamental beam (532
      nm, 14.16 mJ, 100%) is converted to blue (459 nm, 1.71 mJ, 12.1%), green (532 nm,
      7.04 mJ, 49.7%), and red (632 nm, 4.90 mJ, 34.6%), resulting in a total
      conversion efficiency of 96.4%.

PMID- 17514251
TI  - Range-resolved optical detection of honeybees by use of wing-beat modulation of
      scattered light for locating land mines.
AB  - An imaging lidar instrument with the capability of measuring the frequency
      response of a backscattered return signal up to 3.6 kHz is demonstrated. The
      instrument uses a commercial microchip frequency-doubled pulsed Nd:YAG laser with
      a 7.2 kHz pulse repetition rate, a pulse duration of less than 1 ns, and a pulse
      energy of greater than 10 microJ. A 15.2 cm commercial telescope is used to
      collect the backscattered signal, and a photomultiplier tube is used to monitor
      the scattered light. This instrument is designed for range- and angle-resolved
      optical detection of honeybees for explosives and land-mine detection. The
      instrument is capable of distinguishing between the scattered light from
      honeybees and other sources through the frequency content of the return signal
      caused by the wing-beat modulation of the backscattered light. Detection of
      honeybees near a bee hive and spatial mapping of honeybee densities near feeders
      are demonstrated.

PMID- 17514252
TI  - Light-pollution model for cloudy and cloudless night skies with ground-based
      light sources.
AB  - The scalable theoretical model of light pollution for ground sources is
      presented. The model is successfully employed for simulation of angular behavior
      of the spectral and integral sky radiance and/or luminance during nighttime.
      There is no restriction on the number of ground-based light sources or on the
      spatial distribution of these sources in the vicinity of the measuring point
      (i.e., both distances and azimuth angles of the light sources are configurable).
      The model is applicable for real finite-dimensional surface sources with defined
      spectral and angular radiating properties contrary to frequently used point
      source approximations. The influence of the atmosphere on the transmitted
      radiation is formulated in terms of aerosol and molecular optical properties.
      Altitude and spectral reflectance of a cloud layer are the main factors
      introduced for simulation of cloudy and/or overcast conditions. The derived
      equations are translated into numerically fast code, and it is possible to repeat
      the entire set of calculations in real time. The parametric character of the
      model enables its efficient usage by illuminating engineers and/or astronomers in
      the study of various light-pollution situations. Some examples of numerical runs
      in the form of graphical results are presented.

PMID- 17514253
TI  - Adaptively controlled supercontinuum pulse from a microstructure fiber for two
      photon excited fluorescence microscopy.
AB  - Selective fluorescence excitation of specific molecular species is demonstrated
      by using coherent control of two-photon excitation with supercontinuum pulses
      generated with a microstructure fiber. Pulse shaping prior to pulse propagation
      through the fiber is controlled by a self-learning optimization loop so that the
      highest fluorescence signal contrast between two fluorescent proteins is
      obtainable. The self-learning optimization loop successfully controls both the
      optical nonlinarity of the microstructure fiber and the two-photon excitation of
      the fluorescent proteins.

PMID- 17514254
TI  - Image transmission and radiation by truncated linearly polarized multimode fiber.
AB  - We study the use of individual multimode fibers for the purposes of
      microendoscopy. We discuss the question of image decomposition in the several
      modes propagating over the fiber and their scattering at the truncated fiber end.
      We derive analytically the scattering matrix of the "fiber-to-air" interface, we
      quantify the extent of intermodal coupling, and we evaluate the radiation diagram
      from the fiber end. Results show that intermodal coupling is weak, so that it
      appears possible to "capture" an external image and transmit the same through the
      fiber, after appropriate phase correction, without excessive distortion.

PMID- 17514255
TI  - Use of polar decomposition for the diagnosis of oral precancer.
AB  - The Mueller matrix describes all the polarizing properties of a sample and,
      therefore, the optical differences between noncancerous and precancerous tissue
      that may be present within the matrix elements. A high-speed polarimetry system
      that generates 16 (4x4) full Mueller matrices to characterize tissues is
      presented. Feature extraction is done on the Mueller matrix elements resulting in
      depolarization and retardance images by polar decomposition. These are used to
      detect and classify early oral cancers and precancerous changes in epithelium
      such as dysplasia. These images are compared with orthogonal polarization images
      and analyzed in an attempt to identity useful factors for the differentiation
      between cancerous lesions and their benign counterparts. Our results indicate
      that polarimetry has potential as a method for the in vivo early detection and
      diagnosis of oral premalignancy.

PMID- 17514256
TI  - Acoustic grating fringe projector for high-speed and high-precision three
      dimensional shape measurements.
AB  - A new acoustic grating fringe projector (AGFP) was developed for high-speed and
      high-precision 3D measurement. A new acoustic grating fringe projection theory is
      also proposed to describe the optical system. The AGFP instrument can adjust the
      spatial phase and period of fringes with unprecedented speed and accuracy. Using
      rf power proportional-integral-derivative (PID) control and CCD synchronous
      control, we obtain fringes with fine sinusoidal characteristics and realize high
      speed acquisition of image data. Using the device, we obtained a precise phase
      map for a 3D profile. In addition, the AGFP can work in running fringe mode,
      which could be applied in other measurement fields.

PMID- 17514257
TI  - Direct measurement of photon number statistics at telecom wavelengths using a
      charge integration photon detector.
AB  - In optical quantum information technology, a photon number resolving detector
      (PNRD) is the basic device for developing photonic quantum computers. The demands
      for the PNRD are high quantum efficiency and wide dynamic range. We have
      developed a charge integration photon detector (CIPD) with a quantum efficiency
      of 80% at telecom wavelengths. The repetition rate of the CIPD is as low as 40 Hz
      at present, but it can be applied for measurement of short pulses. We report the
      capability of the CIPD for multiphoton counting over 10 photons, its responsivity
      to the short pulses, and its high linearity using a binary intensity modulated
      short pulse (2 ns) train and simultaneous irradiation of two kinds of pulses.

PMID- 17514258
TI  - Resonant frequencies of Fabry-Perot interferometers with ultrathin mirror
      spacings.
AB  - Fabry-Perot interferometers (FPIs) with multilayer dielectric mirrors and mirror
      spacings as low as 0.7% of the operating wavelength are studied. It is shown how
      these low-order FPIs are affected by the phase dispersion characteristics of
      multilayer dielectric mirrors. Because experimental results in the optical regime
      are extremely difficult to obtain, radio frequency experiments are performed with
      coaxial cable FPI structures. Experimental results show excellent agreement with
      theory. These phase effects in FPIs with ultrathin mirror spacings are of great
      interest in the design of tunable microcavities with possible applications in
      optical communications.

PMID- 17514259
TI  - Asymmetric transverse-load characteristics and polarization dependence of long
      period fiber gratings written by a focused CO(2) laser.
AB  - Asymmetric transverse-load characteristics and the polarization dependence of
      long-period fiber gratings (LPFGs) written by high-frequency CO(2) laser pulses
      are investigated in detail. It is demonstrated that the resonant wavelength is
      dependent on the direction of the applied force and on the polarization state of
      the input light; however, the coupling strength is independent of these
      parameters. When a transverse load is applied along different orientations of the
      LPFG, the resonant wavelength may be shifted toward the longer wavelength, the
      shorter wavelength, or hardly shifted, whereas the absolute value of peak
      transmission attenuation is linearly decreased with an increase of the applied
      transverse load, with almost no sensitivity to the load direction. These unique
      transverse-load characteristics and the polarization dependence are due to the
      load-induced birefringence that leads to the rotation of optical principal axes
      in the LPFG.

PMID- 17514260
TI  - Analytical solutions for image orientation changes in prisms.
AB  - Optical prisms are most commonly employed because of their ability to output an
      image of different orientation relative to the input object. Previous papers have
      presented a systematic but numeric approximation for designing a single prism,
      which outputs an image with a specific image orientation. Instead of a numerical
      solution, an exact analytical solution for the same problem is offered. Further,
      how to design prism systems by using off-the-shelf right-angle prisms and roof
      prisms as building blocks to obtain an output image with a specific image
      orientation is addressed. Illustrative examples are given to verify the proposed
      approach and demonstrate its use.

PMID- 17514261
TI  - High-resolution, flat-field, plane-grating, f/10 spectrograph with off-axis
      parabolic mirrors.
AB  - A high-resolution, flat-field, plane-grating, f/10 spectrometer based on the
      novel design proposed by Gil and Simon [Appl. Opt. 22, 152 (1983)] is
      demonstrated. The spectrometer design employs off-axis parabolic collimation and
      camera mirrors in a configuration that eliminates spherical aberrations and
      minimizes astigmatism, coma, and field curvature in the image plane. In
      accordance with theoretical analysis, the performance of this spectrometer
      achieves a high spatial resolution over the large detection area, which is shown
      to be limited only by the quality of its optics and their proper alignment within
      the spatial resolution of a 13 microm x 13 microm pixelated CCD detector. With a
      1500 lines/mm grating in first order, the measured spectral resolving power of
      lambda/Dlambda = 2.5(+/-0.5) x 10(4) allows the clear resolution of the violet
      Ar(I) doublet at 419.07 and 419.10 nm.

PMID- 17514262
TI  - Simulation of the inhomogeneous medium with a self-adapting grid.
AB  - It is difficult to solve the problem of tracing rays through an inhomogeneous
      medium such as the atmosphere or a flowing liquid with the existing methods whose
      refractive distribution cannot be characterized by any combination of formulas. A
      new method is developed to efficiently describe such a medium. The method
      essentially consists of characterizing the inhomogeneous medium with a self
      adapting grid, the cell size of which can be automatically varied according to
      the gradient of the refractive index at each position within the medium. The
      advantage of this method is its capability to trace rays through a medium with
      random refractive distribution in an accurate way. To test its correctness, the
      ray trace through a regular gradient medium has also been made with this method,
      and the results are compared with those from other commercial lens design codes.
      It is shown that for appropriate parameter settings this method can obtain great
      accuracy.

PMID- 17514263
TI  - Circle of least confusion of a spherical reflector.
AB  - A simple, tractable equation is provided for determining the size and location of
      the circle of least confusion of a concave spherical reflector. This method is
      exact for the object at infinity and with wave effects neglected. Designers of
      large radius Arecibo-like telescopes, both radio and optical, with symmetrical,
      spherical primaries should find the method useful. The mathematical results are
      valid for apertures with an angle of incidence up to 45 degrees. Comparisons of
      the location of the disk of least confusion with longitudinal spherical
      aberration and the radius of the disk with transverse spherical aberration are
      presented.

PMID- 17514264
TI  - Determination of large-scale out-of-plane displacements in digital Fourier
      holography.
AB  - A novel approach for the determination of large-scale out-of-plane displacements
      from digital Fourier holograms is presented. The proposed method is invariant to
      lateral object shifts. It is based on the determination of the scaling of the
      reconstructed image that occurs when the recording distance is changed. For a
      precise determination of the scaling factor, we utilize the Mellin transform.
      After the discussion of mathematical and computational issues, experimental
      results are presented to verify the theoretical considerations. The results show
      that displacements of at least up to 8.4% from the initial recording distance can
      be detected with this approach. The displacements could be determined with a
      deviation of typically less than 1.0% from the set values.

PMID- 17514265
TI  - Multipoint laser vibrometer for modal analysis.
AB  - Experimental modal analysis of multifrequency vibration requires a measurement
      system with appropriate temporal and spatial resolution to recover the mode
      shapes. To fully understand the vibration it is necessary to be able to measure
      not only the vibration amplitude but also the vibration phase. We describe a
      multipoint laser vibrometer that is capable of high spatial and temporal
      resolution with simultaneous measurement of 256 points along a line at up to 80
      kHz. The multipoint vibrometer is demonstrated by recovering modal vibration data
      from a simple test object subject to transient excitation. A practical
      application is presented in which the vibrometer is used to measure vibration on
      a squealing rotating disk brake.

PMID- 17514266
TI  - Optical properties of an optically rough coating from inversion of diffuse
      reflectance measurements.
AB  - A method is developed for determining the optical properties of an optically
      rough coating on an opaque substrate from reflectance measurements. A modified
      Kubelka-Munk two- flux model is used to calculate the reflectance of the coating
      as a function of the refractive index, absorption coefficient, scattering
      coefficient, and thickness. The calculated reflectance is then fitted to
      measurements using a spectral projected gradient algorithm, allowing the optical
      properties to be obtained. The technique is applied to titanium dioxide coatings
      on a titanium substrate. Realistic values of refractive index and absorption
      coefficients are generally obtained. Quantities that are useful for solar water
      splitting applications are calculated, including the depth profile of absorption
      and the proportion of the incident photon flux absorbed in the coating under
      solar illumination.

PMID- 17514267
TI  - Electro-optic heterodyne interferometer.
AB  - We propose a new configuration for using a triangle-wave signal to drive the
      electro-optic modulator in an electro-optic heterodyne interferometer system. The
      new configuration is adapted to measure the phase retardation of a wave plate and
      the optical rotation angle of a chiral medium. By adding optic elements, the
      second-harmonic component amplitude of the interferometer photodetector output
      signal became proportional to the phase retardation or optical rotation angle of
      the samples being tested.

PMID- 17514268
TI  - Measurement of aerosol-particle trajectories using a structured laser beam.
AB  - What is believed to be a new concept for the measurement of micrometer-sized
      particle trajectories in an inlet air stream is introduced. The technique uses a
      light source and a mask to generate a spatial pattern of light within a volume in
      space. Particles traverse the illumination volume and elastically scatter light
      to a photodetector where the signal is recorded in time. The detected scattering
      waveform is decoded to find the particle trajectory. A design is presented for
      the structured laser beam, and the accuracy of the technique in determining
      particle position is demonstrated. It is also demonstrated that the structured
      laser beam can be used to measure and then correct for the spatially dependent
      instrument-response function of an optical-scattering-based particle-sizing
      system for aerosols.

PMID- 17514269
TI  - Atomic force microscopy characterization of Zerodur mirror substrates for the
      extreme ultraviolet telescopes aboard NASA's Solar Dynamics Observatory.
AB  - The high-spatial frequency roughness of a mirror operating at extreme ultraviolet
      (EUV) wavelengths is crucial for the reflective performance and is subject to
      very stringent specifications. To understand and predict mirror performance,
      precision metrology is required for measuring the surface roughness. Zerodur
      mirror substrates made by two different polishing vendors for a suite of EUV
      telescopes for solar physics were characterized by atomic force microscopy (AFM).
      The AFM measurements revealed features in the topography of each substrate that
      are associated with specific polishing techniques. Theoretical predictions of the
      mirror performance based on the AFM-measured high-spatial-frequency roughness are
      in good agreement with EUV reflectance measurements of the mirrors after
      multilayer coating.

PMID- 17514270
TI  - Two-dimensional performance of uniform irradiation with the use of an edge
      softened lens array and spectral dispersion.
AB  - A lens array composed of edge-softened elements is used to improve on-target
      irradiation uniformity in the Shenguang II Laser Facility, with which a Fresnel
      pattern of suppressed diffraction peaks is obtained. Additional uniformity can be
      reached by reducing short-wavelength interference speckles inside the pattern
      when the technique of smoothing by spectral dispersion is also used. Two
      dimensional performance of irradiation is simulated and the results indicate that
      a pattern of steeper edges and a flat top can be achieved with this joint
      technique.

PMID- 17514271
TI  - Laser linear encoder with both high fabrication and head-to-scale tolerances.
AB  - We introduce a new configuration for the optical head of a newly developed
      diffractive laser encoder system. This configuration has a high manufacturing
      tolerance and a high head-to-scale alignment tolerance, both of which can enhance
      the wider potential applicability of this newly designed laser encoder. The
      measurement principles of the encoder are discussed and detailed. We optimized
      the grating shape and analyzed the impact of the optical components and their
      arrangement on the measurement error. The head-to-scale alignment tolerance and
      the arrangement of components in the encoder were also determined. Finally, the
      measurement performance was evaluated and analyzed. Under nonenvironmentally
      controlled conditions, the measurement accuracy was found to be 37.3 nm with a
      standard deviation of 25.4 nm.

PMID- 17514272
TI  - All-optical combiner-splitter and gating devices based on straight waveguides.
AB  - A two-mode optical combiner-splitter device is designed based on all straight
      waveguides that maintains the integrity of the two modes during propagation and
      allows for an analytic analysis. The design analysis has the potential to improve
      the precision of the device fabrication. The design is used in an analytic
      optical gate based on a nonlinear Mach-Zehnder interferometer. The design reduces
      the size of a previously proposed device and simplifies its analysis.

PMID- 17514273
TI  - Design and analysis of all-dielectric broadband nonpolarizing parallel-plate beam
      splitters.
AB  - Past research on the all-dielectric nonpolarizing beam splitter is reviewed. With
      the aid of the needle thin-film synthesis method and the conjugate graduate
      refine method, three different split ratio nonpolarizing parallel-plate beam
      splitters over a 200 nm spectral range centered at 550 nm with incidence angles
      of 45 degrees are designed. The chosen materials component and the initial stack
      are based on the Costich and Thelen theories. The results of design and analysis
      show that the designs maintain a very low polarization ratio in the working range
      of the spectrum and has a reasonable angular field.

PMID- 17514274
TI  - Long-term stable device for tuning fiber Bragg gratings.
AB  - It is demonstrated that with a proper choice of embedding material, the composite
      beam bending method constitutes an effective and reliable approach for tuning
      fiber Bragg gratings. A long-term stable device is presented with a dynamic range
      of 80 nm, which exhibits insertion losses smaller than 0.28 dB and small
      variations of the full width at half-maximum.

PMID- 17514275
TI  - Analysis of a two-dimensional photonic bandgap structure fabricated by an
      interferometric lithographic system.
AB  - An interferometric lithographic technique and double exposure method are applied
      to theoretically and experimentally investigate several kinds of 2D periodic
      structures. The shape, lattice symmetries, and lattice constants of the 2D
      structures, for different substrate rotational angles, are obtained from the
      simulated predictions. The shape of the 2D structures can be varied by
      controlling the rotational angle of the substrate and the development process,
      and they are validated experimentally. The variation of the lattice symmetry of
      the 2D structure with the substrate rotational angle is discussed in detail in
      relation to the axial angle and lattice constant. It is found that square,
      circular, rectangular, and elliptical scatterers which are arranged in
      parallelogram, triangular, and square lattices (with different lattice constants)
      can be obtained. The photonic bandgaps for each condition are also investigated.
      When the substrate rotational angles are the same, the normalized frequency
      (omega a/2 pi c) of photonic bandgap structures with an equal filling factor are
      very similar regardless of the interference angle. The results are helpful in
      designing the forbidden frequency when the lattice constant and the scatterer
      shape can be controlled by the interferometric lithographic technique.

PMID- 17514276
TI  - Simulation analysis of the restraining effect of a spatial filter on a hot image.
AB  - Based on the restraining effect that spatial filtering has on the frequency
      spectrum of a beam, from the small-scale focusing theory of Bespalov and Talanov
      (B-T theory) we derive an expression for the pinhole diameter of the spatial
      filter corresponding to the fastest growing frequency. Then, compared with the
      theoretical pinhole diameter of the spatial filter, the restraining effect of the
      spatial filter on a hot image with different pinhole diameters is numerically
      investigated. The numerical results show that, if the pinhole diameter is larger
      than the theoretical one, the hot-image intensity will remain steady; once the
      pinhole diameter becomes smaller than the theoretical one, the hot-image
      intensity will begin to decrease. Moreover, as the pinhole diameter decreases, a
      more prominent restraining effect can be obtained. But reducing the diameter of
      the spatial filter would lead to greater beam energy loss. The parameters of the
      spatial filter must be chosen to guarantee that the scheme fulfills the demand
      for low beam energy loss and a satisfactory restraining effect simultaneously.

PMID- 17514277
TI  - Resolution enhancement by combination of subpixel and deconvolution in miniature
      spectrometers.
AB  - The resolution of a miniature spectrometer with a multichannel detector is
      limited by its throughput. A subpixel deconvolution method is proposed to enhance
      resolution without physically reducing the throughput. The method introduces
      subpixel reconstruction to overcome undersampling during deconvolution
      processing. The experimental result has shown a 36.6% reduction in FWHM of
      spectral lines, indicating the effectiveness of the method.

PMID- 17514278
TI  - Embedded spectroscopic fiber sensor for on-line arc-welding analysis.
AB  - A new fiber sensor system designed for spectroscopic analysis and on-line quality
      assurance of arc-welding processes is presented here. Although several different
      approaches have been considered for the optical capture of plasma emission in arc
      welding processes, they tend to be invasive and make use of optical devices such
      as collimators or photodiodes. The solution proposed here is based on the
      arrangement of an optical fiber, which is used at the same time as the optical
      capturing device and also to deliver the optical information to a spectrometer,
      embedded within an arc-welding torch. It will be demonstrated that, by using the
      shielding gas as a protection for the fiber end, the plasma light emission is
      efficiently collected, forming a sensor system completely transparent and
      noninvasive for the welding operator. The feasibility of the proposed sensor
      designed to be used as the input optics of a welding quality-assurance system
      based on plasma spectroscopy will be demonstrated by means of several welding
      tests.

PMID- 17514279
TI  - Nanoporous structure of a GdF(3) thin film evaluated by variable angle
      spectroscopic ellipsometry.
AB  - As excimer lasers extend to deep-ultraviolet and vacuum-ultraviolet wavelengths
      at 193 and 157 nm, optical coatings experience the challenge of eliminating
      possible environmental contamination, reducing scattering loss, and increasing
      laser irradiation durability. Wide bandgap metal fluorides become the materials
      of choice for the laser optics applications. To understand the optical properties
      of nanostructure fluoride films, thin GdF(3) films grown on CaF(2) (111)
      substrates were evaluated by variable angle spectroscopic ellipsometry. An
      effective medium approximation model was used to determine both the film porosity
      and the surface roughness. Structural evolution of the GdF(3) film was revealed
      with improved ellipsometric modeling, suggesting the existence of multilayer
      structure, a densified bottom layer, middle layers with increasing porosity, and
      a rough surface. The nanostructure of the film and the surface roughness were
      confirmed by atomic force microscopy. The attraction of the nanostructure to
      environmental contamination was experimentally demonstrated.

PMID- 17514280
TI  - Analysis of the interchannel response in a MEMS 1 x N(2) wavelength-selective
      switch.
AB  - A theoretical model based on Fourier optics and the power-coupling overlap
      integral is built to investigate the interchannel response in a micro-electro
      mechanical systems 1xN(2) wavelength-selective switch. The simulation results
      demonstrate that the interchannel response depends significantly on the output
      port location and the radius of curvature of the micromirrors. For the output
      originally aligned with the input along the dispersion direction, it is possible
      to achieve interchannel-response suppression by rotating the two-dimensional (2D)
      collimator array by a slight angle, e.g., 20 degrees. Experimental results under
      different conditions are also shown.

PMID- 17514281
TI  - Orthogonal polarization simultaneous readout for volume holograms with hybrid
      angle and polarization multiplexing in LiNbO(3).
AB  - The orthogonal polarization simultaneous readout technique in a hybrid
      multiplexed memory using angular multiplexing and polarization multiplexing is
      presented. Twenty holograms were hybrid multiplexed in a single LiNbO(3) crystal
      with ten angular positions for angular multiplexing. In each angular position of
      the holographic memory, two images with orthogonal polarization are multiplexed
      in the same spatial location inside the LiNbO(3) via polarization multiplexing.
      These two orthogonally polarized images can be reconstructed simultaneously with
      a linear polarization reading beam, but they can be separated with a polarization
      beam splitter, and accordingly each can be viewed independently. The exposure
      schedule for holographic storage using the proposed hybrid-multiplexing technique
      is derived.

PMID- 17514282
TI  - Infrared target tracking with kernel-based performance metric and eigenvalue
      based similarity measure.
AB  - An infrared target tracking framework is presented that consists of three main
      parts: mean shift tracking, its tracking performance evaluation, and position
      correction. The mean shift tracking algorithm, which is a widely used kernel
      based method, has been developed for the initial tracking for its efficiency and
      effectiveness. A performance evaluation module is applied for the online
      evaluation of its tracking performance with a kernel- based metric to unify the
      tracking and performance metric within a kernel-based tracking framework. Then
      the tracking performance evaluation result is input into a controller in which a
      decision is made whether to trigger a position correction process. The position
      correction module employs a matching method with a new eigenvalue-based
      similarity measure computed from a local complexity degree weighted covariance
      matrix. Experimental results on real-life infrared image sequences are presented
      to demonstrate the efficacy of the proposed method.

PMID- 17514283
TI  - Multiple-step triangular-pattern phase shifting and the influence of number of
      steps and pitch on measurement accuracy.
AB  - We present new extensions of the two-step, triangular-pattern phase-shifting
      method for different numbers of phase-shifting steps to increase measurement
      accuracy and to analyze the influence of the number of phase-shifting steps and
      pitch of the projected triangular intensity-profile pattern on the measurement
      accuracy. Phase-shifting algorithms to generate the intensity ratio, essential
      for surface reconstruction, were developed for each measurement method.
      Experiments determined that higher measurement accuracy can be obtained with a
      greater number of phase-shifting steps and a lower value of pitch, as long as the
      pitch is appropriately selected to be divisible by the number of phase-shifting
      steps and not below an optimal value, where intensity-ratio unwrapping failure
      would occur.

PMID- 17514284
TI  - Design of a broadband highly dispersive pure silica photonic crystal fiber.
AB  - A highly dispersive dual-concentric-core pure silica photonic crystal fiber is
      designed with a maximum chromatic dispersion value of about -9500 ps/(nm km)
      around the 1.56 microm wavelength region and a full width at half-maximum (FWHM)
      of 55 nm. The change in the dispersion-bandwidth product as a function of period
      is carefully studied by using the plane wave expansion method. The coupled mode
      theory matches well with the plane wave expansion method that was used to
      simulate the chromatic dispersion. This kind of a photonic crystal fiber
      structure is suitable for high-dispersion application in phased array antenna
      systems based on photonic crystal fiber arrays.

PMID- 17514285
TI  - Diode-pumped Nd:YAG laser with 38 W average power and user-selectable, flat-in
      time subnanosecond pulses.
AB  - A diode-pumped injection-seeded Nd:YAG laser system with an average output power
      of 38 W is described. The laser operates at 300 Hz with pulse energies up to 130
      mJ. The temporal pulse shape is nominally flat in time and the pulse width is
      user selectable from 350 to 600 ps. In addition, the spatial profile of the beam
      is near top hat with contrast <10%.

PMID- 17514286
TI  - National Ignition Facility laser performance status.
AB  - The National Ignition Facility (NIF) is the world's largest laser system. It
      contains a 192 beam neodymium glass laser that is designed to deliver 1.8 MJ at
      500 TW at 351 nm in order to achieve energy gain (ignition) in a deuterium
      tritium nuclear fusion target. To meet this goal, laser design criteria include
      the ability to generate pulses of up to 1.8 MJ total energy, with peak power of
      500 TW and temporal pulse shapes spanning 2 orders of magnitude at the third
      harmonic (351 nm or 3omega) of the laser wavelength. The focal-spot fluence
      distribution of these pulses is carefully controlled, through a combination of
      special optics in the 1omega (1053 nm) portion of the laser (continuous phase
      plates), smoothing by spectral dispersion, and the overlapping of multiple beams
      with orthogonal polarization (polarization smoothing). We report performance
      qualification tests of the first eight beams of the NIF laser. Measurements are
      reported at both 1omega and 3omega, both with and without focal-spot
      conditioning. When scaled to full 192 beam operation, these results demonstrate,
      to the best of our knowledge for the first time, that the NIF will meet its laser
      performance design criteria, and that the NIF can simultaneously meet the
      temporal pulse shaping, focal-spot conditioning, and peak power requirements for
      two candidate indirect drive ignition designs.

PMID- 17514287
TI  - Birefringence-induced bifocusing for selection of radially or azimuthally
      polarized laser modes.
AB  - We develop a round-trip matrix diagonalization method for quantitative
      description of selection of radially or azimuthally polarized beams by
      birefringence-induced bifocusing in a simple laser resonator. We employ different
      focusing between radially and tangentially polarized light in thermally stressed
      laser rods to obtain low-loss stable oscillation in a radially polarized Laguerre
      Gaussian, LG(0,1)*, mode. We derive a free-space propagator for the radially and
      azimuthally polarized LG(0,1)* modes and explain basic principles of mode
      selection by use of a round-trip matrix diagonalization method. Within this
      method we calculate round-trip diffraction losses and intensity distributions for
      the lowest-loss transverse modes. We show that, for the considered laser
      configuration, the round-trip loss obtained for the radially polarized LG(0,1)*
      mode is significantly smaller than that of the azimuthally polarized mode. Our
      experimental results, obtained with a diode side-pumped Nd:YAG rod in a flat
      convex resonator, confirm the theoretical predictions. We achieved a pure
      radially polarized LG(0,1)* beam with M(2)=2.5 and tens of watts of output power.

PMID- 17514288
TI  - Passively Q-switched Tm(3+)-doped silica fiber lasers.
AB  - By splicing on a length of Ho(3+)-doped silica fiber onto a diode-pumped double
      clad Tm(3+)-doped silica fiber, stable passive Q switching of the Tm(3+)-doped
      silica fiber laser is demonstrated. The formation of Q-switched pulses was found
      to depend on both the length and the position of the Ho(3+)-doped silica fiber
      that was inserted into the fiber laser cavity. For stable Q-switched pulse
      generation, Ho(3+)-doped silica fiber lengths shorter than twice the absorption
      depth must be used. For long Ho(3+)-doped silica fiber lengths, randomly
      generated pulses are observed at operating wavelengths longer than 2090 nm, which
      are attributed to intracavity pumping of the Ho(3+)-doped silica fiber.

PMID- 17514289
TI  - Enhanced second-harmonic generation in an electro-optic controlled periodically
      poled ferroelectric crystal.
AB  - We present a novel design of enhanced second-harmonic generation in a
      periodically poled ferroelectric crystal. It profits from enhanced light
      intensity and slowed group velocity, which occur near photonic band edges through
      electro-optic modulation. The designed structure, with 108 periods and a length
      of 322 microm, can generate a second-harmonic beam whose conversion efficiency is
      2 orders of magnitude larger than the one produced by an equivalent length of
      quasi-phase-matching bulk medium. This result might be beneficial to the
      development of optics integration and compact devices.

PMID- 17514290
TI  - Bulk electro-optic deflector-based switches.
AB  - We propose two novel electro-optic (EO) deflectors based on two new
      nonrectangular geometries: the parabolic and the half-horn configurations. These
      devices not only provide excellent deflection angles, but also have the potential
      to build nonblocking 2 x 2 optical switches. A deflector figure of merit is
      defined, and comparisons with existing EO deflectors are given. Devices
      fabricated in LiTaO(3) demonstrate 3 dB of average insertion loss and 3 degrees
      deflection angles. These results represent the best deflection performances to
      our knowledge reported to date for bulk EO deflectors.

PMID- 17514291
TI  - Retrieval of aerosol properties over land surfaces: capabilities of multiple
      viewing-angle intensity and polarization measurements.
AB  - We investigate the capabilities of different instrument concepts for the
      retrieval of aerosol properties over land. It was found that, if the surface
      reflection properties are unknown, only multiple-viewing-angle measurements of
      both intensity and polarization are able to provide the relevant aerosol
      parameters with sufficient accuracy for climate research. Furthermore, retrieval
      errors are only little affected when the number of viewing angles is increased at
      the cost of the number of spectral sampling points and vice versa. This indicates
      that there is a certain amount of freedom for the instrument design of dedicated
      aerosol instruments. The final choice on the trade-off between the spectral
      sampling and the number of viewing angles should be made taking other factors
      into account, such as instrument complexity and the ability to obtain global
      coverage.

PMID- 17514292
TI  - Fiber optic Raman sensor to monitor the concentration ratio of nitrogen and
      oxygen in a cryogenic mixture.
AB  - A spontaneous Raman scattering optical fiber sensor was developed for a specific
      need of the National Aeronautics and Space Administration (NASA) for long-term
      detection and monitoring of the purity of liquid oxygen (LO(2)) in the oxidizer
      feed line during ground testing of rocket engines. The Raman peak intensity
      ratios for liquid nitrogen (LN(2)) and LO(2) with varied weight ratios
      (LN(2)/LO(2)) were analyzed for their applicability to impurity sensing. The
      study of the sensor performance with different excitation light sources has
      helped to design a miniaturized, cost-effective system for this application. The
      optimal system response time of this miniaturized sensor for LN(2)/LO(2)
      measurement was found to be in the range of a few seconds. It will need to be
      further reduced to the millisecond range for real-time, quantitative monitoring
      of the quality of cryogenic fluids in a harsh environment.

PMID- 17514293
TI  - Photoacoustic tomography using a Mach-Zehnder interferometer as an acoustic line
      detector.
AB  - A three-dimensional photoacoustic imaging method is presented that uses a Mach
      Zehnder interferometer for measurement of acoustic waves generated in an object
      by irradiation with short laser pulses. The signals acquired with the
      interferometer correspond to line integrals over the acoustic wave field. An
      algorithm for reconstruction of a three-dimensional image from such signals
      measured at multiple positions around the object is shown that is a combination
      of a frequency-domain technique and the inverse Radon transform. From images of a
      small source scanning across the interferometer beam it is estimated that the
      spatial resolution of the imaging system is in the range of 100 to about 300 mum,
      depending on the interferometer beam width and the size of the aperture formed by
      the scan length divided by the source-detector distance. By taking an image of a
      phantom it could be shown that the imaging system in its present configuration is
      capable of producing three-dimensional images of objects with an overall size in
      the range of several millimeters to centimeters. Strategies are proposed how the
      technique can be scaled for imaging of smaller objects with higher resolution.

PMID- 17514294
TI  - Feasibility analysis of an epidermal glucose sensor based on time-resolved
      fluorescence.
AB  - The goal of this study is to test the feasibility of using an embedded time
      resolved fluorescence sensor for monitoring glucose concentration. Skin is
      modeled as a multilayer medium with each layer having its own optical properties
      and fluorophore absorption coefficients, lifetimes, and quantum yields obtained
      from the literature. It is assumed that the two main fluorophores contributing to
      the fluorescence at these excitation and emission wavelengths are nicotinamide
      adenine dinucleotide (NAD)H and collagen. The intensity distributions of
      excitation and fluorescent light in skin are determined by solving the transient
      radiative transfer equation by using the modified method of characteristics. The
      fluorophore lifetimes are then recovered from the simulated fluorescence decays
      and compared with the actual lifetimes used in the simulations. Furthermore, the
      effect of adding Poissonian noise to the simulated decays on recovering the
      lifetimes was studied. For all cases, it was found that the fluorescence lifetime
      of NADH could not be recovered because of its negligible contribution to the
      overall fluorescence signal. The other lifetimes could be recovered to within
      1.3% of input values. Finally, the glucose concentrations within the skin were
      recovered to within 13.5% of their actual values, indicating a possibility of
      measuring glucose concentrations by using a time-resolved fluorescence sensor.

PMID- 17514295
TI  - Bandgap-assisted surface-plasmon sensing.
AB  - Surface-plasmon resonance (SPR) is a sensing technique widely used for its label
      free feature. However, its sensitivity is contingent on the divergence angle of
      the excitation beam. The problem becomes pronounced for compact systems when a
      low-cost LED is used as the light source. When the Kretschmann configuration with
      a periodically modulated surface is used, a bandgap appears in the surface
      plasmon dispersion relation. We recognize that the high density of modes on the
      edge of the surface-plasmon bandgap permits the coupling of a wider range of
      incidence angles of excitation photons to surface-plasmon polaritons than what is
      possible in the traditional Kretschmann configuration. Here, the numerical
      simulation illustrates that the sensitivity, detection limit, and reflectivity
      minimum of an amplitude-based SPR bandgap-assisted surface-plasmon sensor are
      almost independent of the divergence angle. Two different bandgap structures are
      compared with the Kretschmann configuration using the rigorous coupled-wave
      analysis technique. The results indicate that the bandgap-assisted sensing
      outperforms traditional SPR sensing when the angular standard deviation of the
      excitation beam is above 1 degree.

PMID- 17514296
TI  - Technical limitations to homodyne detection at audio frequencies.
AB  - Homodyne detection relies on the beat between a relatively strong local
      oscillator (LO) field at the carrier frequency and a signal beam with sidebands
      centered around the carrier frequency. This type of signal detection, or signal
      readout, is widely used in quantum optics applications and is expected to be used
      in advanced interferometric gravitational wave detectors. We investigate
      experimentally the limitations to making such measurements in a laboratory
      environment at audio frequencies. We find that beam jitter noise, electronic
      noise of the photodetectors, and the LO intensity noise can limit the homodyne
      detection in this frequency band, and we discuss potential solutions.

PMID- 17514297
TI  - Diffraction characteristics of a submicrometer grating for a light guide plate.
AB  - The diffraction transmission characteristics of submicrometer gratings (SMGs)
      designed for coupling tricolor light out of a light guide plate (LGP) are
      discussed. Three discrete SMGs are designed for three special wavelengths: red
      (700 nm), green (546.1 nm), and blue (435.8 nm). The propagation direction of the
      output tricolor light is perpendicular to the surface of the LGP and can pass
      through the corresponding pixels of liquid crystal. Calculated by the rigorous
      coupled-wave theory, the first-order transmission efficiency as a function of
      grating depth is found to be approximate to a sinusoidlike curve and can be
      utilized to obtain uniform illumination. The theoretical maximum transmission is
      as much as 44%. The performance of the LGP composed of SMGs is also demonstrated
      by our experiments. Compared with other types of LGP, the present device has the
      advantage of flexible control of illumination angle and wavelengths.
      Additionally, lossy and costly color filters are unnecessary in the proposed
      configuration.

PMID- 17514298
TI  - Production and evaluation of silicon immersion gratings for infrared astronomy.
AB  - Immersion gratings, diffraction gratings where the incident radiation strikes the
      grooves while immersed in a dielectric medium, offer significant compactness and
      performance advantages over front-surface gratings. These advantages become
      particularly large for high-resolution spectroscopy in the near-IR. The
      production and evaluation of immersion gratings produced by fabricating grooves
      in silicon substrates using photolithographic patterning and anisotropic etching
      is described. The gratings produced under this program accommodate beams up to 25
      mm in diameter (grating areas to 55 mm x 75 mm). Several devices are complete
      with appropriate reflective and antireflection coatings. All gratings were tested
      as front-surface devices as well as immersed gratings. The results of the testing
      show that the echelles behave according to the predictions of the scalar
      efficiency model and that tests done on front surfaces are in good agreement with
      tests done in immersion. The relative efficiencies range from 59% to 75% at 632.8
      nm. Tests of fully completed devices in immersion show that the gratings have
      reached the level where they compete with and, in some cases, exceed the
      performance of commercially available conventional diffraction gratings (relative
      efficiencies up to 71%). Several diffraction gratings on silicon substrates up to
      75 mm in diameter having been produced, the current state of the silicon grating
      technology is evaluated.

PMID- 17514299
TI  - Single-pulse fiber Bragg gratings and specific coatings for use at elevated
      temperatures.
AB  - The technique of recording fiber Bragg gratings (FBGs) with single exposure
      pulses during the fiber drawing process allows production of such gratings in
      complex array structures, with high mechanical strength of the fiber and in a
      simple and cost-efficient way. This is of special interest for the growing field
      of fiber sensor applications with FBGs. A general advantage of fiber sensor
      systems is their ability to be used also at elevated temperatures compared with
      conventional electric or electronic sensors. For this purpose, the fiber itself
      as well as the grating structure and the fiber coating should be stable under
      such elevated temperature conditions. We have investigated different coating
      materials and possibilities of making temperature-stable FBGs of types I and II
      in the range of 100 degrees C-1000 degrees C with good reflection efficiency by
      single-pulse exposure during the fiber drawing process.

PMID- 17514300
TI  - Fiber-optical sensor with miniaturized probe head and nanometer accuracy based on
      spatially modulated low-coherence interferogram analysis.
AB  - Fiber-optical sensors have some crucial advantages compared with rigid optical
      systems. They allow miniaturization and flexibility of system setups.
      Nevertheless, optical principles such as low-coherence interferometry can be
      realized by use of fiber optics. We developed and realized an approach for a
      fiber-optical sensor, which is based on the analysis of spatially modulated low
      coherence interferograms. The system presented consists of three units, a
      miniaturized sensing probe, a broadband fiber-coupled light source, and an
      adapted Michelson interferometer, which is used as an optical receiver.
      Furthermore, the signal processing procedure, which was developed for the
      interferogram analysis in order to achieve nanometer measurement accuracy, is
      discussed. A system prototype has been validated thoroughly in different
      experiments. The results approve the accuracy of the sensor.

PMID- 17514301
TI  - Optical fiber array for the delivery of high peak-power laser pulses for fluid
      flow measurements.
AB  - Fiber delivery of 64.7 mJ laser pulses (approximately 6 ns duration) from a Q
      switched Nd:YAG laser operating at 532 nm is demonstrated. A custom diffractive
      optical element was used to shape the laser beam and facilitate coupling into a
      linear fiber array. This launch arrangement achieves an improvement in launch
      efficiency compared with a circular fiber bundle evaluated in previous work and
      the delivery of higher pulse energies is demonstrated. The bundle is capable of
      delivering light of sufficient pulse energy and, importantly, with suitable
      focusability, to generate a thin light sheet for the fluid flow measurement
      technique of particle image velocimetry (PIV). Fiber delivery offers an
      advantage, in terms of optical access, for the application of PIV to enclosed
      measurement volumes, such as the cylinder of a combustion engine.

PMID- 17514302
TI  - Geometric method to measure astigmatism aberration at astronomical telescopes.
AB  - A simple geometrical method to measure the aberration of astigmatism present in
      the wavefront that emerges from a telescope is presented. The method is based on
      the analysis of the external contour of the image of a slightly defocused star.
      An expression elliptical edge is obtained, which links the rms value of Z22 to
      the geometric parameters of the ellipse. This expression is tested as a function
      of introduced defocus and astigmatism aberration in telescopes of the San Pedro
      Martir Observatory. It is shown that the method gives comparable results to
      wavefront tests, being capable of measuring astigmatism values of approximately
      60 nm and larger without the need for auxiliary optics.

PMID- 17514303
TI  - Optical design of the atacama cosmology telescope and the millimeter bolometric
      array camera.
AB  - The Atacama Cosmology Telescope is a 6 m telescope designed to map the cosmic
      microwave background simultaneously at 145, 215, and 280 GHz with arcminute
      resolution. Each frequency will have a 32 by 32 element focal plane array of
      transition edge sensor bolometers. The telescope and the cold reimaging optics
      are optimized for millimeter-wave observations with these sensitive detectors.
      The design of each is described.

PMID- 17514304
TI  - Pattern composed of two-dimensional diffusion dots for showing dynamic images.
AB  - A new type of diffusion pattern is proposed. The proposed patterns are composed
      of 2D diffusion dots. The diffusion dots are created on a photoresist plate by
      recording the image of a local area of a piece of ground glass dot by dot. An
      imaging lens covered by a mask with a slit aperture is used to form the image. By
      changing the orientation of the slit aperture on the mask plane, the diffusion
      dots can have different microintensity distributions for the same incident light
      beam. Therefore the diffusion dots created by the same slit aperture orientation
      show the same brightness, and the diffusion dots created by different slit
      orientations show different brightness for the same illuminating and viewing
      conditions. Thus a proposed diffusion pattern can show dynamic images by changing
      its illuminating or viewing directions. By applying the double-exposure technique
      to the diffusion dots of a pattern, the pattern not only can show dynamic effects
      but also can possess several hidden features for identifying the pattern.
      Therefore the proposed patterns are dynamic and anticounterfeiting.

PMID- 17514305
TI  - Phase tracking with a spatial synchronous method.
AB  - A modified form of a phase tracking method to demodulate a single fringe pattern
      is presented. Phase values from local areas of the interferogram are recovered by
      means of a spatial synchronous technique instead of solving the set of nonlinear
      equations obtained from the implementation of the ordinary algorithm. This
      results in a significant speed improvement of the method. Additionally, the
      robustness against noise is maintained, and the sensitivity to contrast
      variations is decremented with respect to the phase tracking technique.

PMID- 17514307
TI  - Aberration evaluation of alignment optics in lithographic tools by use of a step
      height structure highly sensitive to the asymmetry of an optical image.
AB  - To satisfy the increasing demand for extremely tight overlay accuracy in
      semiconductor manufacturing processes, all the measurement error factors in
      alignment systems and overlay measurement tools need be identified and
      eliminated. The principle of most alignment systems is based on image processing
      of target marks on the wafer under bright-field illumination. Although the
      phenomenon that the sensitivity to the alignment error varies with the step
      height (SH) of the mark has been known and used for evaluating the performance of
      the alignment optics, no investigation has been made into the origin and the
      physical mechanism of the phenomenon. We propose a simplified optical model that
      can account for the origin of the asymmetric image and clarify its relation to
      the SHs. The model is validated with simulation and experimental results. The
      improved performance of an alignment system using marks with optimally designed
      SHs is demonstrated.

PMID- 17514308
TI  - Simple parameter determination for twisted nematic liquid-crystal display.
AB  - A simple and accurate measurement method for determining the cell parameters of a
      twisted nematic liquid-crystal display (TN-LCD) is proposed. Based on the
      measurement of the maximum reflectance and the maximum transmittance of a TN-LCD
      by rotating the polarizer at a particular angle, between the front director of
      the liquid crystals and the transmission axis of the polarizer, the cell gap and
      the twist angle can be determined according to the Jones matrix theory, and the
      twist sense can also be determined easily by applying an external small voltage
      to slightly change the effective refractive index of the liquid crystal.

PMID- 17514309
TI  - Decoupling refractive index and geometric thickness from interferometric
      measurements of a quartz sample using a fourth-order polynomial.
AB  - A Michelson interferometer setup was used to determine refractive index and
      thickness of a fused-quartz sample with no knowledge of either parameter. At
      small angles, < 10 degrees, the interferometer equation follows a fourth-order
      polynomial in the sample refractive index alone, effectively decoupling the
      sample thickness from the equation. The incident angle of the He-Ne laser beam
      versus fringe shift was fitted to the polynomial, and its coefficients obtained.
      These were used to determine refractive index to within 6 x 10(-4) of the known
      value with an accuracy of +/- 1.3%. Sample thickness was determined to an
      accuracy of +/-2.5%. Reproducibility of the rotating table was determined to be
      +/-2 x 10(-3) degrees.

PMID- 17514306
TI  - Measurement of the optical parameters of the Virgo interferometer.
AB  - The Virgo interferometer, aimed at detecting gravitational waves, is now in a
      commissioning phase. Measurements of its optical properties are needed for the
      understanding of the instrument. We present the techniques developed for the
      measurement of the optical parameters of Virgo. These parameters are compared
      with the Virgo specifications.

PMID- 17514310
TI  - Testing of large optical surfaces with subaperture stitching.
AB  - Based on our previously proposed subaperture stitching and localization (SASL)
      algorithm, we present strategies and a prototype for testing of large optical
      surfaces with subaperture stitching. First, several strategies are introduced to
      deal with new problems when applying the SASL algorithm to large surfaces. The
      uncertainty of the lateral scale of the interferometer is compensated in the same
      manner as that of the radii of best-fit spheres in the algorithm. Then the coarse
      fine stitching strategy is proposed to stitch tens of subapertures efficiently.
      Second, a prototype for testing of large surfaces with subaperture stitching is
      developed with a welded structural base. The model of kinematics is built to
      determine the initial configuration of each subaperture, according to the records
      of nulling motion. The uncertainty of linear motion is required to be no more
      than 1 mm, taking advantage of the large range of convergence of the SASL
      algorithm. Finally we present an experiment to verify the validity of the method
      and the prototype. A spherical surface is tested and successfully stitched with
      37 subapertures.

PMID- 17514311
TI  - Omnidirectional reflection in several frequency ranges of one-dimensional
      photonic crystals.
AB  - We investigate omnidirectional reflection from higher-order gaps in one
      dimensional photonic crystals. Moreover, we present a designing criterion for
      omnidirectional reflection from several distinct gaps simultaneously, using only
      a single photonic crystal with a constant period. We show that for practical
      values of photonic crystals parameters, several relatively large omnidirectional
      gaps may be obtained. As an example, we demonstrate an omnidirectional reflector
      that exhibits two distinct wide omnidirectional ranges at near-infrared
      wavelengths. This omnidirectional reflector that operates in several ranges of
      wavelengths may have various potential applications.

PMID- 17514312
TI  - Imaging diffractometer with holographic encoding enhancements for laser sensing
      and characterization.
AB  - What is believed to be a novel holographic optical encoding scheme has been
      developed to enhance the performance of laser sensors designed for the
      measurement of wavelength and angular trajectory. A prototype holographic imaging
      diffractometer has been created to reconstruct holographic cueing patterns
      superimposed in the focal plane of wide-angle scene imagery. Based on
      experimental pattern metric measurements at the focal plane, a theoretical model
      is used to compute the laser source wavelength and its apparent propagation
      direction within the sensor's field of view. The benefits of incorporating
      holographic enhancements within an imager-based sensor architecture are
      discussed.

PMID- 17514313
TI  - Absolute phase measurements using geometric constraints between multiple cameras
      and projectors.
AB  - The method of phase shift with the projection of multiple cyclic patterns enables
      3D measurement that is highly accurate, dense, and fast. However, this
      measurement is only possible for the wrapped phase value, which has ambiguities
      in its multiples of cycles. Two particular problems are that conventional methods
      require additional patterns to be projected to determine the absolute phase and
      that unwrapping the phase tends to fail where depth varies abruptly. Two methods
      are proposed: the first is to determine the absolute phase without additional
      patterns being projected by observing the projected pattern with multiple cameras
      and applying the geometric constraints between them, and the second is to prevent
      failure in unwrapping the phase by referring to continuities in the relative
      phases of multiple projected patterns. The proposed methods were achieved with a
      3D scanner that can measure approximately a 180 degrees field of view within 0.5
      s, with an accuracy of 0.14 mm in depth.

PMID- 17514314
TI  - Three-dimensional angle measurement based on propagation vector analysis of
      digital holography.
AB  - We propose what we believe to be a novel method for highly accurate three
      dimensional (3D) angle measurement based on propagation vector analysis of
      digital holography. Three-dimensional rotations in space can be achieved by use
      of a CCD camera and a multifacet object, which reflects an incident wave into
      different directions. The propagation vectors of the reflected waves from the
      object can be extracted by analyzing the object spectrum of the recorded
      hologram. Any small rotation of the object will induce a change in the
      propagation vectors in space, which can then be used for 3D angle measurement.
      Experimental results are presented to verify the idea.

PMID- 17514315
TI  - New approach for the design of an optical square pulse generator.
AB  - What is believed to be a new approach for the design and analysis of a
      reconfigurable optical square pulse generator using the concept of temporal
      optical integration and the digital signal processing method is presented. The
      reconfigurable square pulse generator is synthesized using compact active
      semiconductor-based waveguide technology, and it consists simply of the cascade
      of a tunable microring resonator (or a tunable all-pole filter) and a tunable
      asymmetrical Mach-Zehnder interferometer (or a tunable all-zero filter). The
      reconfigurable generator can convert an input picosecond pulse (i.e., soliton or
      Gaussian pulse) into an optical square pulse. The pulse width of the generated
      square pulse can be adjusted by controlling the time delay of a variable delay
      element in the tunable all-zero filter. The reconfigurable generator can convert
      an input picosecond pulse train into return-to-zero (RZ) and non-return-to-zero
      (NRZ) signals with square pulse shapes. The repetition rates of the generated RZ
      and NRZ signals can be varied by adjusting the bit period of the input picosecond
      pulse train, the input pulse width, and the time delay of the variable delay
      element. The effect of the deviation of the parameter values on the generator
      performance is also studied.

PMID- 17514316
TI  - Phase-to-amplitude data page conversion for holographic storage and optical
      encryption.
AB  - A new phase-to-amplitude data page conversion method is proposed for efficient
      recovery of the data encoded in phase-modulated data pages used in holographic
      storage and optical encryption. The method is based on the interference between
      the data page and its copy shifted by an integral number of pixels. Key
      properties such as Fourier plane homogeneity, bit error rate, and positioning
      tolerances are investigated by computer modeling, and a comparison is provided
      with amplitude-modulated data page holographic storage with and without static
      phase masks. The feasibility and the basic properties of the proposed method are
      experimentally demonstrated. The results show that phase-modulated data pages can
      be used efficiently with reduced system complexity.

PMID- 17514317
TI  - Specklegram in a multiple-mode fiber and its dependence on longitudinal modes of
      the laser source.
AB  - A specklegram in a multimode fiber (MMF) has successfully been used as a sensor
      for detecting external disturbance. Our experiments showed that the sensitivity
      in the sensor with a multiple longitudinal-mode laser as its source was much
      higher than that with a single longitudinal-mode laser. In addition, the near
      field pattern observations indicated that the coupling between different
      transverse modes in the MMF is quite weak. Based on the experimental results, a
      theoretical model for the speckle formation is proposed, taking a bend-caused
      phase factor into consideration. It is shown in the theoretical analysis that the
      interferences between different longitudinal modes make a larger contribution to
      the specklegram signals.

PMID- 17514318
TI  - Switchable multiwavelength ytterbium-doped double-clad fiber laser based on a
      multimode fiber grating.
AB  - A simple switchable multiwavelength double-clad fiber laser using a multimode
      fiber Bragg grating (MMFG) as a wavelength selective component is demonstrated.
      The MMFG is fabricated directly in the active double-clad fiber, resulting in low
      splicing loss and compact configuration. By properly adjusting the polarization
      controller in the cavity, the double-clad fiber laser can stably operate at
      different multiwavelength states at room temperature. At lower pump levels, the
      laser can be switched between single- and dual-wavelength operations, while at
      higher pump levels the laser can switch between dual- and triple-wavelength
      operations. The slope efficiency of the system is 41% with the maximum output
      power of 6.2 W.

PMID- 17514319
TI  - Littrow-type external-cavity blue laser for holographic data storage.
AB  - An external-cavity laser with a wavelength of 405 nm and an output of 80 mW has
      been developed for holographic data storage. The laser has three states: the
      first is a perfect single mode, whose coherent length is 14 m; the second is a
      three-mode state with a coherent length of 3 mm; and the third is a six-mode
      state with a coherent length of 0.3 mm. The first and second states are available
      for angular-multiplexing recording; all states are available for coaxial
      multiplexing recording. Due to its short wavelength, the recording density is
      higher than that of a 532 nm laser.

PMID- 17514320
TI  - High-efficiency generation of a continuous-wave single-frequency 780 nm laser by
      external-cavity frequency doubling.
AB  - We demonstrated a 670 mW continuous-wave single-frequency laser source at 780 nm
      by using external-cavity-enhanced second-harmonic generation of a seeded fiber
      amplifier in periodically poled lithium niobate. A maximum second-harmonic
      conversion efficiency of 58% was achieved. The source can work stably over 1 h by
      locking the frequency-doubling cavity, while the power stability is less than 2%.

PMID- 17514321
TI  - Compact efficient eye-safe intracavity optical parametric oscillator with a
      shared cavity configuration.
AB  - We present a compact efficient eye-safe intracavity optical parametric oscillator
      pumped by a passively Q-switched Nd:YAG laser in a shared cavity configuration. A
      signal pulse of 3.3 mJ energy at a 1573 nm wavelength with a peak power of 150 kW
      was achieved. The effective conversion efficiency with respective to the
      optimized 1064 nm Q-switched pulse energy was as high as 51%.

PMID- 17514322
TI  - Numerical study of particle-size distributions retrieved from angular light
      scattering data using an evolution strategy with the Fraunhofer approximation.
AB  - An algorithm is presented based on an evolution strategy to retrieve a particle
      size distribution from angular light-scattering data. The analyzed intensity
      patterns are generated using the Mie theory, and the algorithm retrieves a series
      of known normal, gamma, and lognormal distributions by using the Fraunhofer
      approximation. The distributions scan the interval of modal size parameters 100 <
      or = alpha < or = 150. The numerical results show that the evolution strategy can
      be successfully applied to solve this kind of inverse problem, obtaining a more
      accurate solution than, for example, the Chin-Shifrin inversion method, and
      avoiding the use of a priori information concerning the domain of the
      distribution, commonly necessary for reconstructing the particle size
      distribution when this analytical inversion method is used.

PMID- 17514323
TI  - Fourier-transform cavity-enhanced absorption spectroscopy using an incoherent
      broadband light source.
AB  - A cavity-enhanced absorption setup employing an incoherent broadband light source
      was used in combination with a Fourier-transform spectrometer to measure the spin
      forbidden B-band of gaseous oxygen at approximately 688 nm and several weak
      absorption transitions of water vapor in the same spectral region at room
      temperature in ambient air. The experiments demonstrate that the sensitivity of a
      Fourier-transform spectrometer can be significantly improved by increasing the
      effective path length, while retaining a rather small sample volume. In
      comparison with a single-pass absorption measurement, we report a path-length
      enhancement factor of 200 and an improvement of the signal-to-noise ratio of
      approximately 6 in the present cavity-enhanced absorption experiment. The
      practical advantages and limitations of this novel approach are outlined and
      potential applications are briefly discussed.

PMID- 17514324
TI  - Noncontact optical imaging in mice with full angular coverage and automatic
      surface extraction.
AB  - During the past decade, optical imaging combined with tomographic approaches has
      proved its potential in offering quantitative three-dimensional spatial maps of
      chromophore or fluorophore concentration in vivo. Due to its direct application
      in biology and biomedicine, diffuse optical tomography (DOT) and its fluorescence
      counterpart, fluorescence molecular tomography (FMT), have benefited from an
      increase in devoted research and new experimental and theoretical developments,
      giving rise to a new imaging modality. The most recent advances in FMT and DOT
      are based on the capability of collecting large data sets by using CCDs as
      detectors, and on the ability to include multiple projections through recently
      developed noncontact approaches. For these to be implemented, we have developed
      an imaging setup that enables three-dimensional imaging of arbitrary shapes in
      fluorescence or absorption mode that is appropriate for small animal imaging.
      This is achieved by implementing a noncontact approach both for sources and
      detectors and coregistering surface geometry measurements using the same CCD
      camera. A thresholded shadowgrammetry approach is applied to the geometry
      measurements to retrieve the surface mesh. We present the evaluation of the
      system and method in recovering three-dimensional surfaces from phantom data and
      live mice. The approach is used to map the measured in vivo fluorescence data
      onto the tissue surface by making use of the free-space propagation equations, as
      well as to reconstruct fluorescence concentrations inside highly scattering
      tissuelike phantom samples. Finally, the potential use of this setup for in vivo
      small animal imaging and its impact on biomedical research is discussed.

PMID- 17514325
TI  - Three-dimensional time-resolved optical mammography of the uncompressed breast.
AB  - Optical tomography is being developed as a means of detecting and specifying
      disease in the adult female breast. We present a series of clinical three
      dimensional optical images obtained with a 32-channel time-resolved system and a
      liquid-coupled interface. Patients place their breasts in a hemispherical cup to
      which sources and detectors are coupled, and the remaining space is filled with a
      highly scattering fluid. A cohort of 38 patients has been scanned, with a variety
      of benign and malignant lesions. Images show that hypervascularization associated
      with tumors provides very high contrast due to increased absorption by
      hemoglobin. Only half of the fibroadenomas scanned could be observed, but of
      those that could be detected, all but one revealed an apparent increase in blood
      volume and a decrease in scatter and oxygen saturation.

PMID- 17514326
TI  - Biophysical modeling of forward scattering from bacterial colonies using scalar
      diffraction theory.
AB  - A model for forward scattering from bacterial colonies is presented. The colonies
      of interest consist of approximately 10(12) - 10(13) individual bacteria densely
      packed in a configuration several millimeters in diameter and approximately 0.1
      0.2 mm in thickness. The model is based on scalar diffraction theory and accounts
      for amplitude and phase modulation created by three macroscopic properties of the
      colonies: phase modulation due to the surface topography, phase modulation due to
      the radial structure observed from some strains and species, and diffraction from
      the outline of the colony. Phase contrast and confocal microscopy were performed
      to provide quantitative information on the shape and internal structure of the
      colonies. The computed results showed excellent agreement with the experimental
      scattering data for three different Listeria species: Listeria innocua, Listeria
      ivanovii, and Listeria monocytogenes. The results provide a physical explanation
      for the unique and distinctive scattering signatures produced by colonies of
      closely related Listeria species and support the efficacy of forward scattering
      for rapid detection and classification of pathogens without tagging.

PMID- 17514327
TI  - Effect of surface roughness on determination of tissue optical properties
      obtained by diffusion approximation.
AB  - A nylon bar with different surface roughness is used as a simulation sample of
      biological tissue for the determination of optical properties by using the
      spatially resolved steady-state diffuse reflection technique. The results
      obtained indicate that surface roughness has some effects on the determination of
      the optical properties of the nylon bar. The determined reduced scattering
      coefficient decreases with the decrease of the surface roughness of the nylon bar
      and goes to a constant for the lower surface roughness, and the determined
      absorption coefficient increases with the decrease of the surface roughness of
      the nylon bar. Consequently, the optical properties of the tissues obtained by
      the spatially resolved steady-state diffuse reflection technique should be
      modified.

PMID- 17514328
TI  - Zintl phases for thermoelectric devices.
AB  - By converting waste heat into electricity and improving the efficiency of
      refrigeration systems, thermoelectric devices could play a significant role in
      solving today's energy problems. Increasing the thermoelectric efficiency (as
      measured by the thermoelectric material's figure-of-merit, zT) is critical to the
      development of this technology. Complex Zintl phases, in particular, make ideal
      candidates for thermoelectric materials because the necessary "electron-crystal,
      phonon-glass" properties can be engineered with an understanding of the Zintl
      chemistry. A recent example is the discovery that Yb(14)MnSb(11), a transition
      metal Zintl compound, has twice the zT as the material currently in use at NASA.
      This perspective outlines a strategy to discover new high zT materials in Zintl
      phases, and presents results pointing towards the success of this approach.

PMID- 17514329
TI  - Development of new transition metal catalysts for the oxidation of a hydroxamic
      acid with in situ Diels-Alder trapping of the acyl nitroso derivative.
AB  - New transition metal catalysts have been prepared and applied for in situ
      formation of acyl nitroso dienophiles.

PMID- 17514330
TI  - Unravelling the chemical nature of copper cuprizone.
AB  - During the last 50 years, formation of the highly chromogenic copper cuprizone
      complex has been exploited for spectrophotometric determinations of copper
      although the precise chemical nature of the resulting species has never been
      ascertained; we eventually show here, in contrast to current opinion, that copper
      cuprizone is a copper(III)complex.

PMID- 17514331
TI  - Hydrothermal syntheses and structural characterizations of organic-inorganic
      hybrid materials of the M(II)-ligand/vanadium oxide system (M(II) = Mn(II),
      Cu(II) and Zn(II); ligand = 2,2'-bipyridine and 1,10-phenanthroline).
AB  - Three organic-inorganic hybrid compounds [Mn(bpy)V(bpy)V(3)O(11)] (bpy = 2,2'
      bipyridine) (1), [Cu(bpy)V(2)O(6)] (2) and [Zn(phen)3][V(2)O(6)].10H(2)O (phen =
      1,10-phenanthroline) (3) have been synthesized hydrothermally. Single crystal X
      ray diffraction analyses revealed that compound 1 is the first example of bpy
      units coordinating to different transition metals in one molecule. Compound 2 is
      a new isomer of [Cu(bpy)V(2)O(6)] which was named the gamma-isomer by us. In
      compound 3, a 2-D water sheet with big holes filled by the "naked" [V(4)O(12)](4
      ) clusters is found.

PMID- 17514332
TI  - Synthesis and preliminary DNA-binding studies of diimineplatinum(II) complexes
      containing 3- or 4-pyridineboronic acid.
AB  - A series of platinum(II) complexes of the type [Pt(NN)(pyB)2](NO3)2 (NN = bipy,
      phen; pyB = 3- or 4-pyridineboronic acid) were successfully prepared and fully
      characterised by 1D- and 2D-multinuclear NMR spectroscopy and ESI-MS. Using VT 1H
      NMR spectroscopy, rotational isomers for [Pt(NN)(3-pyB)2](NO3)2 were identified
      and the free energies of activation for rotation of 3-pyB about the Pt-N bond
      were determined to be DeltaG++310) = 69.2 +/- 0.1 kJ mol(-1) and DeltaG++(305) =
      66.0 +/- 0.1 kJ mol(-1) for [Pt(bipy)(3-pyB)2](NO3)2 and [Pt(phen)(3
      pyB)2](NO3)2, respectively. The 3- and 4-pyB ligands readily deboronate in
      boiling H2O to afford [Pt(NN)(py)2](NO3)2; the structure of [Pt(phen)(py)2](2+)
      (as its PF6- salt) was confirmed by X-ray crystallography. Preliminary thermal
      denaturation studies revealed only minimal interactions between
      [Pt(NN)(pyB)2](NO3)2 and calf-thymus DNA and is attributed to hydroxylation of
      the boronic acid groups at pH 7.4 to afford the corresponding zwitterionic
      boronate species. This was confirmed by means of variable pH 1H and 11B{1H} NMR
      spectroscopy.

PMID- 17514333
TI  - Investigation into the reactivity of the coordinatively unsaturated
      phosphonodithioato [Ni(MeOpdt)2] towards 2,4,6-tris(2-pyridyl)-1,3,5-triazine:
      goals and achievements.
AB  - The reaction between the coordinatively unsaturated phosphonodithioato complex
      [Ni(MeOpdt)2] (1) [MeOpdt = (MeO)(4-MeOC(6)H(4))PS2-] and tptz [2,4,6-tris(2
      pyridyl)-1,3,5-triazine] has been investigated. Spectrophotometric and
      conductometric titrations showed the formation of a neutral and an ionic species,
      i.e. [Ni(MeOdtp)2(tptz)] (2) and [Ni(tptz)2](MeOdtp)2 (3), in correspondence to 1
      : 1 and 2 : 1 tptz : ratios, respectively. XRD studies confirmed the formation of
      both complexes isolated in the compounds 2.MeOH and 3.4H(2)O. In the neutral
      complex 2 the central Ni(II) ion features a distorted octahedral coordination,
      achieved through three N-atoms of tptz and three S-atoms belonging to two MeOpdt
      anions, one of which unexpectedly acts as a monodentate S-donor. In 3.4H(2)O, the
      two phosphonodithioato anions are non-coordinating and counterbalance the charge
      of the [Ni(tptz)2](2+) distorted octahedral complex. From the reaction 2 of with
      I2 and Br2, crystals of [Ni(tptz)2](I3)2 (5) and [Ni(tptz)Br(micro-Br)]2 (6) have
      been obtained. The dinuclear complex 6 features a structure showing tubular
      canals with openings of about 6 x 6 A.

PMID- 17514334
TI  - New anionic cobalt complexes using highly hindered bis-amides with varying donor
      abilities as ligands.
AB  - Four potential tetradentate ligands of formulae 1,2-bis-(3,5-di-tert-butyl-2
      hydroxybenzamido)ethane (H(4)L(1), 1), 1,2-bis-(3,5-di-tert-butyl-2
      hydroxybenzamido)propane (H(4)L(2), 2), 1,2-bis-(3,5-di-tert-butyl-2
      hydroxybenzamido)benzene (H(4)L(3), 3) and 1,8-bis-(3,5-di-tert-butyl-2
      hydroxybenzamido)naphthalene (H(4)L(4), 4) have been prepared and the crystal
      structures of three of them (1, 3 and 4) determined by single crystal X-ray
      diffraction. The investigation of their complexing ability toward Co(II) afforded
      the compounds of formulae [Co(III)(L(3))Na(I)(H(2)O)(2)] (5),
      [Co(III)(L(n))Li(I)(H(2)O)2] with n = 1 (6), 2 (7) and 3 (8) and
      [Co(II)(L(4))Li(I)(2)] (9). Complexes 5-8 are square planar Co(III) species, as
      corroborated by the crystal structure of 5. In this compound, two amide-nitrogen
      and two phenolate-oxygen atoms of a fully deprotonated (L(3))(4-) anion build a
      slightly distorted square planar surrounding around the cobalt atom, the Co-N
      distances [1.858(3) and 1.861(3) A] being somewhat longer than the Co-O ones
      [1.798(3) and 1.801(3) A]. Magnetic and 1H NMR data at room temperature for 6-8
      support the occurrence of an intermediate S = 1 low-lying state for the Co(III)
      center which is stabilized by the strong donating ability of the fully
      deprotonated bis-amidate ligands. In the case of the compound with the
      naphthalene derivative (9), the analytical and spectroscopic data suggest the
      occurrence of a low spin Co(II) complex. The weakening of the ligand field
      strength of the tetradentate bis-amidate ligand in the naphthalene derivative (5
      6-5 ring-membered fused chelate) when compared to the situation in complexes 5-8
      (5-5-5 ring-membered fused chelate) would account for this feature.

PMID- 17514335
TI  - A novel 3D cyano-bridged mixed-valence CoII/CoIII canted antiferromagnet
      constructed from defective cubanes. Synthesis, X-ray structure and magnetic
      properties.
AB  - The hydrothermal reaction of 2-pyrimidine-carboxamide, CoCl2.6H(2)O and
      K3[Co(CN)6] affords a novel mixed-valence Co(II)/Co(III) 3D complex
      K[Co3(CN)6(ox)(H(2)O)2].H2O, which contains cyano-bridged Co(7) defective cubanes
      connected by oxalate and cyanide bridging groups and behaves as a canted
      antiferromagnet with Tc = 17.5 K.

PMID- 17514336
TI  - The long and short of it: the influence of N-carboxyethyl versusN-carboxymethyl
      pendant arms on in vitro and in vivo behavior of copper complexes of cross
      bridged tetraamine macrocycles.
AB  - A cross-bridged cyclam ligand bearing two N-carboxymethyl pendant arms (1) has
      been found to form a copper(II) complex that exhibits significantly improved
      biological behavior in recent research towards (64)Cu-based radiopharmaceuticals.
      Both the kinetic inertness and resistance to reduction of Cu-1 are believed to be
      relevant to its enhanced performance. To explore the influence of pendant arm
      length on these properties, new cross-bridged cyclam and cyclen ligands with
      longer N-carboxyethyl pendant arms, 2 and 4, and their respective copper(II)
      complexes have been synthesized. Both mono- as well as di-O-protonated forms of
      Cu-2 have also been isolated and structurally characterized. The spectral and
      structural properties of Cu-2 and Cu-4, their kinetic inertness in 5 M HCl, and
      electrochemical behavior have been obtained and compared to those of their N
      carboxymethyl-armed homologs, Cu-1 and Cu-3. Only the cyclam-based Cu-1 and Cu-2
      showed unusually high kinetic inertness towards acid decomplexation. While both
      of these complexes also exhibited quasi-reversible Cu(II)/Cu(I) reductions, Cu-2
      is easier to reduce by a substantial margin of +400 mV, bringing it within the
      realm of physiological reductants. Similarly, of the cyclen-based complexes, Cu-4
      is also easier to reduce than Cu-3 though both reductions are irreversible.
      Biodistribution studies of (64)Cu-labeled 2 and 4 were performed in Sprague
      Dawley rats. Despite comparable acid inertness to their shorter-armed congeners,
      both longer-armed ligand complexes have poorer bio-clearance properties. This
      inferior in vivo behavior may be a consequence of their higher reduction
      potentials.

PMID- 17514337
TI  - Multiporphyrin coordination arrays based on complexation of magnesium(II)
      porphyrins with porphyrinylphosphine oxides.
AB  - Di- and triporphyrin arrays consisting of 5,15-diphenylporphyrinatomagnesium(II)
      (MgDPP) coordinated to free-base and Ni(II) porphyrinyl mono- and bis-phosphine
      oxides, as well as the self-coordinating diphenyl[10,20
      diphenylporphyrinatomagnesium(II)-5-yl]phosphine oxide [MgDPP(Ph(2)PO)], were
      synthesised in excellent yields and characterised by various spectroscopic
      techniques. Phosphine oxides stabilise Mg(II) coordination to porphyrins and the
      resulting complexes have convenient solubilities, while the Ni(II) complexes
      exhibit interesting intramolecular fluorescence quenching behaviour. The binding
      constant of MgDPP to triphenylphosphine oxide (5.3 +/- 0.1 x 10(5) M(-1)) and the
      very high self-association constant of [MgDPP(Ph(2)PO)] (5.5 +/- 0.5 x 10(8) M(
      1)) demonstrate the strong affinity of phosphine oxides towards Mg(II)
      porphyrins. These complexes are the first strongly bound synthetic Mg(II)
      multiporphyrin complexes and could potentially mimic the "special pair" in the
      photosynthetic reaction centre.

PMID- 17514338
TI  - Experimental electron density study of a complex between copper(II) and the
      antibacterial quinolone family member ciprofloxacin.
AB  - An experimental charge density study of a 1 : 1 complex of Cu-cfx (cfx =
      ciprofloxacin), 1 [Cu(cfx)(H(2)O)(3)]SO4.2H(2)O, has been performed using single
      crystal X-ray diffraction data collected at 100 K using conventional Mo Kalpha
      radiation. Metal-ligand (ML) bonds and hydrogen bonds (HBs) have been analysed
      using topological analysis of the electron density with the atoms in molecules
      (AIM) approach. The copper atom binds to two oxygen atoms in one end of the
      zwitterionic form of the cfx molecule, in addition to forming bonds with three
      water molecules, forming a square pyramidal coordination geometry. AIM
      decomposition of the experimental electron density establishes that the copper
      atom binds more strongly to the cfx molecule than to the water molecules,
      suggesting that the latter can be detached leaving behind a reactive, water-free
      Cu-cfx complex available for interaction with e.g. a macromolecular site. AIM
      analysis of the extensive hydrogen bond pattern reveals that the positively
      charged N-end of the zwitterionic cfx forms a relatively strong N-H-O hydrogen
      bond implying that this region of cfx may play an important role in the docking
      process in the active site. Visualisation and statistics of selected density
      derived properties on the molecular surface of the isolated cfx molecule vs its
      metal complexed counterpart points out regions of potential reactivity. The
      effect of the fluorine atom is to expand the negative region of the electrostatic
      potential, while the nitrogen end is heavily electropositive and willingly
      donates to--for molecular docking purposes--relatively strong hydrogen bonding.
      The Cu atom is highlighted as a potentially highly reactive site which is likely
      to interact strongly with any given negative ligand.

PMID- 17514339
TI  - cis-trans photoisomerization in [Ru(DIP)2(MeOH)2][OTf]2: synthesis, NMR, X-ray
      structure of the trans-isomer and photophysical properties.
AB  - The first trans-ruthenium complex trans-[Ru(DIP)2(MeOH)2][OTf]2 (1b, where DIP =
      4,7-diphenyl-1,10-phenanthroline) incorporating a pi-extended ligand was prepared
      via two methods: either photolysis of cis-[Ru(DIP)2(OTf)2] in MeOH-Et(2)O or via
      crystallization from MeOH-Et(2)O in direct sunlight. The X-ray molecular
      structure of is reported and confirmed the trans geometry of the title compound.
      The cis-trans isomerization process was monitored by 1H-NMR and showed that 1b
      reverts back to cis-[Ru(DIP)2(MeOH)2][OTf]2 (1a) in methanol-d4 after 15 h at 55
      degrees C or several days at room temperature. The absorption spectra recorded in
      MeOH showed a bathochromic shift of the MLCT band of the trans-isomer 1b relative
      to that of the cis complex 1a. Interestingly at 77 K the emission spectrum of 1b
      is red shifted compared to the cis analog 1a. A rational explanation in terms of
      the energy of the excited states in the cis- and trans-isomers is proposed to
      explain this behavior.

PMID- 17514340
TI  - Solid state structure and solution behaviour of organoselenium(II) compounds
      containing 2-{E(CH2CH2)2NCH2}C6H4 groups (E = O, NMe).
AB  - Cleavage of the Se-Se bond in [2-{O(CH(2)CH(2))(2)NCH(2)}C(6)H(4)](2)Se(2) (1)
      and [2-{MeN(CH(2)CH(2))(2)NCH(2)}C(6)H(4)](2)Se(2) (2) by treatment with
      SO(2)Cl(2), bromine or iodine (1 : 1 molar ratio) yielded [2
      {O(CH(2)CH(2))(2)NCH(2)}C(6)H(4)]SeX [X = Cl (3), Br (4), I (5)] and [2
      {MeN(CH(2)CH(2))(2)NCH(2)}C(6)H(4)]SeI (6). The compounds were characterized in
      solution by NMR spectroscopy (1H, 13C, 15N, 77Se, 2D experiments). The solid
      state molecular structures of 1-3, 4.HBr, 5 and 6 were established by single
      crystal X-ray diffraction. In all cases T-shaped coordination geometries, i.e.
      (C,N)SeSe (1, 2), (C,N)SeX (3, 5, 6; X = halogen) or CSeBr(2) (4.HBr), were
      found. Supramolecular associations in crystals based on hydrogen contacts are
      discussed.

PMID- 17514341
TI  - A new dinuclear heme-copper complex derived from functionalized protoporphyrin
      IX.
AB  - A new biomimetic model for the heterodinuclear heme/copper center of respiratory
      oxidases is described. It is derived from iron(III) protoporphyrin IX by covalent
      attachment of a Gly-L-His-OMe residue to one propionic acid substituent and an
      amino-bis(benzimidazole) residue to the other propionic acid substituent of the
      porphyrin ring, yielding the Fe(III) complex 1, and subsequent addition of a
      copper(II) or copper(I) ion, according to needs. The fully oxidized
      Fe(III)/Cu(II) complex, 2, binds azide more strongly than 1, and likely contains
      azide bound as a bridging ligand between Fe(III) and Cu(II). The two metal
      centers also cooperate in the reaction with hydrogen peroxide, as the peroxide
      adducts obtained at low temperature for 1 and 2 display different optical
      features. Support to this interpretation comes from the investigation of the
      peroxidase activity of the complexes, where the activation of hydrogen peroxide
      has been studied through the phenol coupling reaction of p-cresol. Here the
      presence of Cu(II) improves the catalytic performance of complex 2 with respect
      to 1 at acidic pH, where the positive charge of the Cu(II) ion is useful to
      promote O-O bond cleavage of the iron-bound hydroperoxide, but it depresses the
      activity at basic pH because it can stabilize an intramolecular hydroxo bridge
      between Fe(III) and Cu(II). The reactivity to dioxygen of the reduced complexes
      has been studied at low temperature starting from the carbonyl adducts of the
      Fe(II) complex, 3, and Fe(II)/Cu(I) complex, 4. Also in this case the adducts
      derived from the Fe(II) and Fe(II)/Cu(I) complexes, that we formulate as Fe(III)
      superoxo and Fe(III)/Cu(II)-peroxo exhibit slightly different spectral
      properties, showing that the copper center participates in a weak interaction
      with the dioxygen moiety.

PMID- 17514342
TI  - Structural diversity in gallium(III) complexes of the tripodal triarsine
      MeC(CH2AsMe2)3.
AB  - The preparation and crystal structures of the first examples of gallium halide
      complexes with the tripodal arsine, MeC(CH(2)AsMe(2))3, reveal three distinctly
      different coordination modes for the ligand; the neutral [{micro(3)
      MeC(CH(2)AsMe(2))3-kappaAs:kappaAs':kappaAs''}(GaI(3))3] with the triarsine
      coordinating to three GaI(3) units, [{Me(2)AsCH(2)C(Me)(CH(2)AsMe(2))2
      kappa(2)AsAs'}GaCl(2)][GaCl(4)] involving bidentate chelation to a GaCl2+
      cationic unit with the third As donor atom uncoordinated, and
      [{MeC(CH(2)AsMe(2))3-kappaAs:kappa(2)As'As''}(GaCl3)(GaCl2)][GaCl4] in which the
      triarsine forms a bidentate chelate to the GaCl2+ unit and the third As donor
      atom binds to a further GaCl3 unit.

PMID- 17514344
TI  - Naltrexone's suppressant effects on drinking are limited to the first 3 months of
      treatment.
AB  - RATIONALE: Twelve weeks of naltrexone significantly improves drinking outcomes in
      alcoholics; however, the clinical benefits of naltrexone decline shortly after
      treatment is discontinued. OBJECTIVE: The present study investigated whether
      extended treatment with naltrexone significantly improved drinking outcomes.
      METHODS: One hundred forty-six alcohol-dependent patients received broad spectrum
      treatment or motivational enhancement therapy and either 12 or 24 weeks of
      naltrexone. The primary dependent variables were percent days abstinent and
      percent heavy drinking days. RESULTS: Using an intention-to-treat analysis, there
      were no significant differences in percent days abstinence or percent heavy
      drinking days at the end of phase 2 between patients who received 24 weeks of
      treatment with naltrexone (chi = 63.23) or patients who received 12 weeks of
      treatment with naltrexone followed by 12 weeks of treatment with placebo (chi =
      65.82). Similarly, the average percent heavy drinking days was not significantly
      different at the end of phase 2 between the group that received 24 weeks of
      naltrexone (chi = 21.9) and the group that received 12 weeks of naltrexone
      followed by 12 weeks of placebo (chi = 22.14). Medication compliance was low in
      the second phase of the study. Drinking outcomes declined with declining
      compliance whether patients were taking naltrexone or placebo. CONCLUSIONS: The
      results of this study suggest that administering naltrexone beyond an initial 12
      weeks of treatment may not be beneficial to all patients and should be
      administered along with close medical monitoring to insure compliance.

PMID- 17514345
TI  - Acute severe pancreatitis: contrast-enhanced sonography.
AB  - Early assessment and differentiation of oedematous acute pancreatitis and
      necrotizing or severe acute pancreatitis allow distinct therapeutic algorithms.
      Spiral computed tomography is currently considered the gold standard for staging
      of acute severe pancreatitis. Conventional transabdominal ultrasound plays only a
      limited role in the staging of acute pancreatitis. The problem is that with this
      procedure a detection of pancreatic necrosis is difficult because it cannot
      assess organ perfusion. Through the use of contrast-enhancers, however, even
      ultrasound can nowadays examine the vascularization behaviour of the pancreas and
      liver parenchyma in sufficient detail. The aim of the present update article is
      to explain the usefulness of contrast-enhanced ultrasound in the detection of
      parenchymal necrosis in patients with acute severe pancreatitis.

PMID- 17514346
TI  - A targeted deletion upstream of Snrpn does not result in an imprinting defect.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) result from the
      disturbance of imprinted gene expression within human chromosome 15q11-q13. Some
      cases of PWS and AS are caused by microdeletions near the SNRPN gene that disrupt
      a regulatory element termed the imprinting center (IC). The IC has two functional
      components; an element at the promoter of SNRPN involved in PWS (PWS-IC) and an
      element 35 kilobases (kb) upstream of SNRPN involved in AS (AS-IC). To further
      understand the function of the IC, we sought to create a mouse model for AS-IC
      mutations. We have generated two deletions at a location analogous to that of the
      human AS-IC. Neither deletion produced an imprinting defect as indicated by DNA
      methylation and gene expression analyses. These results indicate that no elements
      critical for AS-IC function in mouse reside within the 12.8-kb deleted region and
      suggest that the specific location of the AS-IC is not conserved between human
      and mouse.

PMID- 17514347
TI  - Germline methylation patterns inferred from local nucleotide frequency of
      repetitive sequences in the human genome.
AB  - Given the genomic abundance and susceptibility to DNA methylation, interspersed
      repetitive sequences in the human genome can be exploited as valuable resources
      in genome-wide methylation studies. To learn about the relationships between DNA
      methylation and repeat sequences, we performed a global measurement of CpG
      dinucleotide frequencies for interspersed repetitive sequences and inferred
      germline methylation patterns in the human genome. Although extensive CpG
      depletion was observed for most repeat sequences, those in the proximity to CpG
      islands have been relatively removed from germline methylation being the
      potential source of germline activation. We also investigated the CpG depletion
      patterns of Alu pairs to see whether they might play an active role in germline
      methylation. Two kinds of Alu pairs, direct or inverted pairs classified
      according to the orientation, showed contrast CpG depletion patterns with respect
      to separating distance of Alus, i.e., as two Alu elements are more closely spaced
      in a pair, a higher extent of CpG depletion was observed in inverted orientation
      and vice versa for directly repetitive Alu pairs. This suggests that specific
      organization of repetitive sequences, such as inverted Alu pairs, might play a
      role in triggering DNA methylation consistent with a homology-dependent
      methylation hypothesis.

PMID- 17514348
TI  - A growth QTL (Pbwg1) region of mouse chromosome 2 contains closely linked loci
      affecting growth and body composition.
AB  - Previous QTL studies have identified 24 QTLs for body weight and growth from 3 to
      10 weeks after birth in an intersubspecific backcross mouse population between
      C57BL/6J and wild Mus musculus castaneus that has 60% of the body size of
      C57BL/6J. The castaneus allele at the most potent QTL (Pbwg1) on proximal
      chromosome 2 retards growth. In this study we have developed a congenic strain
      with a 44.1-Mb interval containing the castaneus allele at Pbwg1 by recurrent
      backcrossing to C57BL/6J. The congenic mouse developed was characterized by
      significantly higher body weight gain between 1 and 3 weeks of age and lower
      weight of white fat pads at 10 weeks of age than C57BL/6J. However, no clear
      difference in body weight at 1-10 weeks of age was observed between congenic and
      C57BL/6J strains. QTL analysis with 269 F(2) mice between the two strains did not
      identify any QTLs for body weight at 1, 3, 6, and 10 weeks of age, but it
      discovered eight closely linked QTLs affecting body weight gain from 1 to 3 weeks
      of age, lean body weight, weight of white fat pads, and body length within the
      Pbwg1 region. The castaneus alleles at all fat pad QTLs reduced the phenotypes,
      whereas at the remaining growth and body composition QTLs, they increased the
      trait values. These results illustrate that Pbwg1, which initially appeared to be
      a single locus, was resolved into several loci with opposite effects on the
      composition traits of overall body weight. This gives a reason for the loss of
      the Pbwg1 effect found in the original backcross population.

PMID- 17514349
TI  - Management of spontaneous haemorrhagic intracranial vertebrobasilar dissection:
      review of 21 consecutive cases.
AB  - INTRODUCTION: Haemorrhagic intracranial vertebrobasilar dissection is an uncommon
      cause of nontraumatic subarachnoid haemorrhage (SAH) and accounts for only 1-10%
      of non-traumatic SAH. Treatment in the acute phase is considered to be essential
      because of the high risk of rebleeding and the consequent unfavourable outcome.
      However, the location, the potential for involvement of eloquent vessels and the
      histopathological characteristics of the vessel wall make treatment demanding
      from both a technical and anatomical point of view. We report our experience in
      the management of this disease. PATIENTS AND TREATMENTS: From 1989 to June 2006,
      we managed 21 patients with spontaneous haemorrhagic dissection located in the
      intracranial vertebrobasilar system, 13 patients were treated using an
      endovascular approach, 1 by surgical clipping, and 7 were managed conservatively.
      RESULTS: Among the 13 patients treated endovascularly, 7 underwent proximal
      occlusion, 4 underwent parent artery embolization at the site of dissection, and
      2 underwent endovascular trapping. Severe, treatment-related complications due to
      dislodgement of the thrombus during the procedure occurred in 1 patient, who then
      died from brainstem ischaemia. One patient died from severe pneumonia and one
      patient was left disabled from vasospastic ischaemia resulting from severe
      initial SAH. The remaining 10 patients had satisfactory outcomes: none rebled
      after treatment and when discharged they had Karnovsky scores of 80-100. Of the 7
      conservatively treated patients, three died of rebleeding and four were
      discharged with Karnovsky scores of 50-100. One patient, who was treated
      surgically, was discharged with a Karnovsky of 90. CONCLUSION: The high rate of
      rebleeding and consequent mortality among the patients treated conservatively
      argues for treatment in the acute phase. Treatment should be guided by each
      patient's angiomorphology, clinical condition and the experience of the
      neurosurgical/neuroradiological team. Options include endovascular or surgical
      trapping of the dissection and proximal occlusion and embolisation of the parent
      artery at the site of the dissection.

PMID- 17514350
TI  - Standards of training in endovascular neurointerventional therapy : as approved
      by the ESNR, EBNR, UEMS Section of Neurosurgery and EANS (February 2007).
      Enclosed the standards of practice as endorsed by the WFITN.

PMID- 17514351
TI  - Sporadic malignant nerve sheath tumour of the oculomotor nerve.
AB  - Malignant peripheral nerve sheath tumours (MPNST) are exceedingly rare in an
      intracranial location. In this report clinical and pathological evidence for the
      diagnosis of a MPNST arising from of the oclumotor nerve is presented. To our
      knowledge this is the first such case reported in the medical literature.

PMID- 17514352
TI  - Segmental unfused basilar artery with kissing aneurysms: report of three cases
      and literature review.
AB  - Basilar artery "fenestration" is the result of a failed fusion of the bilateral
      longitudinal neural arteries and can be associated with a saccular aneurysm,
      which typically arises at the proximal juncture of the unfused segment. "Kissing"
      aneurysms at this site, i.e. two aneurysms arising from the proximal junction of
      the unfused segment of the basilar artery pointing anteriorly and posteriorly are
      reported to be exceedingly rare. We present three patients with this rare
      condition, all of them being treated by endovascular techniques.

PMID- 17514354
TI  - Useful 'junk': Alu RNAs in the human transcriptome.
AB  - Alu elements are the most abundant repetitive elements in the human genome; they
      have amplified by retrotransposition to reach the present number of more than one
      million copies. Alu elements can be transcribed in two different ways, by two
      independent polymerases. 'Free Alu RNAs' are transcribed by Pol III from their
      own promoter, while 'embedded Alu RNAs' are transcribed by Pol II as part of
      protein- and non-protein-coding RNAs. Recent studies have demonstrated that both
      free and embedded Alu RNAs play a major role in post transcriptional regulation
      of gene expression, for example by affecting protein translation, alternative
      splicing and mRNA stability. These discoveries illustrate how a part of the 'junk
      DNA' content of the human genome has been recruited to important functions in
      regulation of gene expression.

PMID- 17514353
TI  - Calcium-mediated activation of PI3K and p53 leads to apoptosis in thyroid
      carcinoma cells.
AB  - The molecular mechanism responsible for cadmium-induced cell death in thyroid
      cancer cells (FRO) is unknown. We demonstrated that apoptosis of FRO cells
      induced by cadmium was concentration and time dependent. Cadmium caused the rapid
      elevation of intracellular calcium and induced phosphorylation of Akt, p53, JNK,
      ERK and p38. Inhibition of PI3K/Akt attenuated the cadmium-induced apoptosis, but
      the inhibition of JNK inhibitor, ERK or p38 aggravated it, indicating that
      activation of PI3K/Akt was a pro-apoptosis signal in response to cadmium
      treatment, whereas the activation of stress-activated protein kinase JNK, ERK and
      p38 functioned as survival signals to counteract the cadmium-induced apoptosis.
      Buffering of the calcium response attenuated mitochondrial impairment, recovered
      the cadmium-activated Akt, p53, JNK, ERK and p38, and subsequently blocked the
      apoptosis. These results suggested that apoptosis induced by cadmium in FRO cells
      was initiated by the rapid elevation of intracellular calcium, followed by
      calcium-mediated activation of PI3K/Akt and mitochondrial impairment.

PMID- 17514355
TI  - The role of hypoxia-inducible factors in cancer.
AB  - Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor that
      mediates the adaptive responses to hypoxia by effecting the transcription of
      numerous hypoxia-inducible genes. HIF is frequently overexpressed in solid
      tumors, and the transactivation of HIF targets in transformed cells provides a
      distinct survival advantage. Accordingly, the upregulation of HIF correlates with
      increased progression or aggressiveness of the cancer and poor prognosis. In
      addition to the induction of HIF by hypoxia, its expression is induced by the
      loss of tumor suppressors VHL, PTEN, TSC1/2, PML, and SDH, as well as by the
      increased activity of PI3K and/or MAPK signaling pathways, underscoring the
      significance of HIF in oncogenesis.

PMID- 17514356
TI  - The mechanisms of action of valproate in neuropsychiatric disorders: can we see
      the forest for the trees?
AB  - After more than 40 years of clinical use, the mechanisms of action of valproate
      in epilepsy, bipolar disorder and migraine are still not fully understood.
      However, recent findings reviewed here shed new light on the cellular effects of
      valproate. Beyond the enhancement of gamma-aminobutyric acid-mediated
      neurotransmission, valproate has been found to affect signalling systems like the
      Wnt/beta-catenin and ERK pathways and to interfere with inositol and arachidonate
      metabolism. Nevertheless, the clinical relevance of these effects is not always
      clear. Valproate treatment also produces marked alterations in the expression of
      multiple genes, many of which are involved in transcription regulation, cell
      survival, ion homeostasis, cytoskeletal modifications and signal transduction.
      These alterations may well be relevant to the therapeutic effects of valproate,
      and result from its enhancement of activator protein-1 DNA binding and direct
      inhibition of histone deacetylases, and possibly additional, yet unknown,
      mechanism(s). Most likely, both immediate biochemical and longer-term genomic
      influences underlie the effects of valproate in all three indications.

PMID- 17514357
TI  - Alternative exon usage selectively determines both tissue distribution and
      subcellular localization of the acyl-CoA thioesterase 7 gene products.
AB  - Acyl-CoA thioesterases (ACOTs) catalyze the hydrolysis of acyl-CoAs to free fatty
      acids and coenzyme A. Recent studies have demonstrated that one gene named Acot7,
      reported to be mainly expressed in brain and testis, is transcribed in several
      different isoforms by alternative usage of first exons. Strongly decreased levels
      of ACOT7 activity and protein in both mitochondria and cytosol was reported in
      patients diagnosed with fatty acid oxidation defects, linking ACOT7 function to
      regulation of fatty acid oxidation in other tissues. In this study, we have
      identified five possible first exons in mouse Acot7 (Acot7a-e) and show that all
      five first exons are transcribed in a tissue-specific manner. Taken together,
      these data show that the Acot7 gene is expressed as multiple isoforms in a tissue
      specific manner, and that expression in tissues other than brain and testis is
      likely to play important roles in fatty acid metabolism.

PMID- 17514358
TI  - Caffeine analogs: biomedical impact.
AB  - Caffeine, widely consumed in beverages, and many xanthine analogs have had a
      major impact on biomedical research. Caffeine and various analogs, the latter
      designed to enhance potency and selectivity toward specific biological targets,
      have played key roles in defining the nature and role of adenosine receptors,
      phosphodiesterases, and calcium release channels in physiological processes. Such
      xanthines and other caffeine-inspired heterocycles now provide important research
      tools and potential therapeutic agents for intervention in Alzheimer's disease,
      asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have
      activity as analgesics, antiinflammatories, antitussives, behavioral stimulants,
      diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety,
      hypertension, certain drug interactions, and withdrawal symptoms.

PMID- 17514359
TI  - Glutamine stimulates translation of uncoupling protein 2mRNA.
AB  - Uncoupling protein 2 (UCP2) belongs to a family of transporters/exchangers of the
      mitochondrial inner membrane. Using cell lines representing natural sites of UCP2
      expression (macrophages, colonocytes, pancreatic beta cells), we show that UCP2
      expression is stimulated by glutamine at physiological concentrations. This
      control is exerted at the translational level. We demonstrate that the upstream
      open reading frame (ORF1) in the 5' untranslated region (5'UTR) of the UCP2 mRNA
      is required for this stimulation to take place. Cloning of the 5' UTR of the UCP2
      mRNA in front of a GFP cDNA resulted in a reporter gene with which GFP expression
      could be induced by glutamine. An effect of glutamine on translation of a given
      mRNA has not been identified before, and this is the first evidence for a link
      between UCP2 and glutamine, an amino acid oxidized by immune cells or intestinal
      epithelium and playing a role in the control of insulin secretion.

PMID- 17514360
TI  - Anticonvulsant, antiepileptogenic, and antiictogenic pharmacostrategies.
AB  - Pharmacological concepts tailored to status epilepticus, to epileptogenesis
      following acquired brain insults, and to ictogenesis in established epilepsy vary
      considerably and should ideally be directed at those pathophysiological
      mechanisms that presumably underly these conditions. Currently known important
      molecular targets include voltage-gated sodium and calcium channels, the gamma
      aminobutyric acid (GABA) system and ionotropic glutamate receptors. Metabotropic
      glutamate receptors, potassium channels, and neurotransmitters such as
      acetylcholine, glycine, and monoamines are beyond the scope of this review. In
      status epilepticus, immediate failure of GABAergic inhibition occurs, and
      administration of benzodiazepines and barbiturates displays the pharmacostrategic
      mainstay. In epileptogenesis within limbic structures, the most important
      underlying pathophysiological mechanisms currently discussed are transient loss
      of inhibition and aberrant mossy fiber sprouting. Both processes may be
      facilitated by N-methy-D: -aspartat (NMDA) receptor regulation. NMDA antagonists
      may exhibit antiepileptogenic properties in experimental animals, but reliable
      data in humans are lacking. In established epilepsy, voltage-gated ion channels
      and impairment of GABAergic functions contribute to mechanisms facilitating
      ictogenesis. Blockade of sodium and calcium channels and enhancement of GABAergic
      inhibition are currently the most important tools to prevent the occurrence of
      seizures.

PMID- 17514361
TI  - Arterial thrombosis and thalidomide.
AB  - Arterial emboli are largely a reflection of cardiac disease. Thalidomide is an
      antiangiogenic drug used in cancer therapy. Venous thrombosis incidence increased
      during treatment with thalidomide. We reported arterial thrombosis in two cases
      with multiple myeloma implemented in thalidomide treatment. Standard emergency
      intervention was applied. In the postoperative period, enoxiparine was given to
      all the patients. Warfarin treatment was started in the level of INR 2-2,5. ASA
      with a dose of 100 mg/day was added to the treatment. In conclusion, this side
      effect of the use of thalidomide should be taken into consideration while doing
      examinations with respect to the etiology in arterial thromboembolism and because
      of this vascular complication that threatens life; we suggest stopping the
      thalidomide treatment.

PMID- 17514362
TI  - Capitation and racial and ethnic differences in use and cost of public mental
      health services.
AB  - This study investigated racial and ethnic differences in the probability of
      mental health service use and costs of treatment before and after the
      implementation of capitated financing. Models were created to test effects on
      utilization and costs of African American, Latinos, and white mental health
      consumers. As service use and costs declined under capitation, Latino, and white
      levels of use and cost tended to converge. African American utilization patterns
      in the capitated areas tended to parallel their white counterparts. Differential
      rejection by, or exclusion of, African American and Latino consumers did not
      appear to occur in response to capitation.

PMID- 17514363
TI  - The PNPase, exosome and RNA helicases as the building components of
      evolutionarily-conserved RNA degradation machines.
AB  - The structure and function of polynucleotide phosphorylase (PNPase) and the
      exosome, as well as their associated RNA-helicases proteins, are described in the
      light of recent studies. The picture raised is of an evolutionarily conserved RNA
      degradation machine which exonucleolytically degrades RNA from 3' to 5'. In
      prokaryotes and in eukaryotic organelles, a trimeric complex of PNPase forms a
      circular doughnut-shaped structure, in which the phosphorolysis catalytic sites
      are buried inside the barrel-shaped complex, while the RNA binding domains create
      a pore where RNA enters, reminiscent of the protein degrading complex, the
      proteasome. In some archaea and in the eukaryotes, several different proteins
      form a similar circle-shaped complex, the exosome, that is responsible for 3' to
      5' exonucleolytic degradation of RNA as part of the processing, quality control,
      and general RNA degradation process. Both PNPase in prokaryotes and the exosome
      in eukaryotes are found in association with protein complexes that notably
      include RNA helicase.

PMID- 17514364
TI  - Extrapancreatic neural plexus invasion by carcinomas of the pancreatic head
      region: evaluation using thin-section helical CT.
AB  - PURPOSE: The aim of this study was to determine the computed tomographic (CT)
      criteria for diagnosing the second portion of the extrapancreatic neural plexus
      (PLX-II) invasion by carcinoma of the pancreatic head region on thin-section
      helical CT. MATERIALS AND METHODS: A total of 41 patients with carcinoma of the
      pancreatic head region (17 in the pancreas, 24 in the lower common bile duct)
      underwent three-phase helical CT (collimation 5 mm; reconstruction 2.5 mm) before
      surgery. Two criteria were established for the assessment of the PLX-II running
      between the superior mesenteric artery (SMA) and the medial margin of the
      uncinate process: criterion A: assessment of the area around the SMA and inferior
      pancreaticoduodenal artery; criterion B: assessment of the jejunal trunk.
      RESULTS: PLX-II invasion was pathologically confirmed in 19 patients with
      pancreatobiliary carcinoma. For criterion A, all 19 patients with positive PLX-II
      invasion and 20 of the 22 with negative PLX-II invasion were correctly diagnosed
      (sensitivity 100%; specificity 91%; accuracy 95%). For criterion B, 3 of the 17
      patients with positive PLX-II invasion and all 20 with negative PLX-II invasion
      were correctly diagnosed (sensitivity 18%; specificity 100%; accuracy 62%). The
      two false-positive cases using criterion A were correctly diagnosed using
      criterion B. CONCLUSION: Thin-section helical CT provides sufficient diagnostic
      ability regarding PLX-II invasion by carcinoma of the pancreatic head region.

PMID- 17514365
TI  - Comparisons of bone mass measurements on various skeletal sites including
      quantitative ultrasonography of the calcaneus for assessing age-related losses,
      their correlations, and diagnostic agreement using the Japanese and WHO criteria
      for osteoporosis.
AB  - PURPOSE: The aim of this study was to compare age-related bone losses and
      correlations among several bone mass measurements and to evaluate diagnostic
      agreement among them using the Japanese and WHO criteria for osteoporosis.
      MATERIALS AND METHODS: A total of 846 women (mean +/- SD: age 54 +/- 9 years)
      were evaluated. Bone mineral densities of the lumbar spine, femoral neck, and
      calcaneus were measured by dual X-ray absorptiometry and distal radius by
      peripheral computed tomography. Quantitative ultrasonography (QUS) parameters of
      the calcaneus were also measured. The age-related bone losses after 50 years of
      age and correlations among bone mass results were evaluated using linear
      regression analysis. Diagnostic agreement was evaluated by kappa statistics.
      RESULTS: The annual losses ranged from 1.0% to 1.6%. The correlation coefficients
      ranged from 0.54 to 0.78. The kappa scores ranged from 0.52 to 0.30 for all
      subjects using the Japanese criteria and from 0.38 to 0.15 using the WHO
      criteria. CONCLUSION: Bone mass measurements including QUS on various skeletal
      sites documented age-related changes similarly, and their bone masses correlated
      moderately. The diagnostic agreements among them were fair to poor. To screen out
      women with a risk of osteoporosis, it is important to choose which technique to
      use and which skeletal site to measure.

PMID- 17514366
TI  - Assessment of diaphragmatic motion after lung resection using magnetic resonance
      imaging.
AB  - PURPOSE: The aim of this study was to assess quantitatively the impairment of
      diaphragmatic motion after lung resection, with special reference to the location
      of the resected lobe, duration of the postoperative period, and patient posture.
      We used magnetic resonance imaging to make the assessments. MATERIALS AND
      METHODS: In 44 patients (29 men, 15 women; mean age 62.2 years) with lung cancer,
      diaphragmatic motion was measured during maximum deep, slow breathing using a
      spoiled gradient-recalled echo sequence before and after lung resection. The
      study group consisted of 34 patients who were examined using a 1.5-T unit in the
      supine position and 10 patients using a vertically open 0.5-T unit in both the
      sitting and supine positions. The influence of surgery site and patient posture
      on diaphragmatic motion after lung resection was investigated. RESULTS: In all
      cases after lung resection, diaphragmatic motion on the operated side was
      significantly decreased (P < 0.001), and that on the nonoperated side was
      significantly increased (P = 0.045). After left upper lobectomy and right
      bilobectomy, the diaphragmatic motion on the operated side was significantly
      decreased (P < 0.001), and that of the other side was significantly increased (P
      < 0.001). The diaphragmatic motion was not significantly changed after right
      middle lobectomy. The diaphragmatic motion on the operated side was impaired
      significantly more (P = 0.035) in the supine position than in the sitting
      position. CONCLUSION: After lobe resection, diaphragmatic motion was impaired
      more significantly in the supine than in the sitting position; and it differed
      according to the location of the resected lobe. The improvement in diaphragmatic
      function after lobectomy was observed over a period of 3-24 months.

PMID- 17514367
TI  - Percutaneous ipsilateral portal vein embolization using a modified four-lumen
      balloon catheter with fibrin glue: initial clinical experience.
AB  - PURPOSE: The purpose of the present study was to show the feasibility and safety
      of ipsilateral portal vein embolization (PVE) using an improved four-lumen
      balloon catheter with fibrin glue. MATERIALS AND METHODS: To improve the
      ipsilateral PVE with fibrin glue, we modified a commercially available four-lumen
      balloon catheter to create a catheter comprising one lumen with a catheter tip
      for a guidewire, one lumen for an occlusion balloon, and two lumens, each with a
      side-hole just proximal to the balloon. Eight patients had hepatobiliary disease
      (three with bile duct carcinoma, two with gallbladder carcinoma, one with
      hepatocellular carcinoma, one with Caroli disease, and one with metastatic
      carcinoma). RESULTS: All embolization procedures were technically successful.
      After embolization, the volume of the future remnant liver increased a mean of
      131%. There was no inadvertent embolization of portal vein branches and no major
      procedure-related complications. CONCLUSION: Our method is potentially easier and
      safer than the traditional ipsilateral method with fibrin glue using a three
      lumen balloon catheter because the fourth lumen makes possible the use of a
      guidewire to access the targeted portal vein and measurement of any portal vein
      pressure elevation following PVE via the fourth lumen.

PMID- 17514368
TI  - Angiomyofibroblastoma-like tumor (cellular angiofibroma) in the male inguinal
      region.
AB  - Angiomyofibroblastoma-like tumor is a rare mesenchymal tumor involving the male
      genital tract. We report a case of an angiomyofibroblastoma-like tumor that arose
      in the subcutaneous tissue of the left inguinal region in a 50-year-old man.
      Ultrasonography of the region demonstrated a well-circumscribed subcutaneous
      mass. Intralesional fat was revealed on magnetic resonance images. Although these
      imaging features are nonspecific, radiological findings enable considering the
      diagnosis of angiomyofibroblastoma-like tumor.

PMID- 17514369
TI  - Pelvic inflammatory disease with periappendicitis in a pediatric patient.
AB  - Pelvic inflammatory disease (PID) is generally a disease of young, sexually
      active patients. However, there have been few reports of computed tomography (CT)
      and the histopathologic findings of periappendicitis with PID in children. We
      present a case of PID with periappendicitis in a 12-year-old girl. Her CT
      findings are described, and the histopathologic findings of periappendicitis are
      discussed.

PMID- 17514370
TI  - Experience of high-dose-rate brachytherapy for head and neck cancer treated by a
      customized intraoral mold technique.
AB  - Radiotherapy of head and neck cancer has become more successful with the advances
      in treatment modalities and use of a multidisciplinary approach. Higher quality
      treatment and a team approach to radiotherapy have thus been required for head
      and neck cancer. This study presents the clinical experience of high-dose-rate
      (HDR) brachytherapy for head and neck cancer treated by a customized intraoral
      mold technique. Two patients are reported for whom we created dental prostheses
      as the radiation carriers for HDR brachytherapy of their head and neck cancers.
      HDR brachytherapy with the dental prostheses reported here was feasible and
      effective for eradicating the head and neck cancer. It has been demonstrated that
      HDR brachytherapy using a customized intraoral technique can be a treatment
      option for patients who are not candidates for surgery or external irradiation.
      It is strongly suggested that specialized dentists are needed who are familiar
      with not only the anatomy and function of the head and neck region but also
      radiotherapy. Dental radiologists should take responsibility for constructing
      irradiation prostheses. If they do, they have the potential to improve the
      quality of life of patients who undergo radiotherapy for head and neck cancer.

PMID- 17514371
TI  - Laser-guided computed tomography puncture system: simulation experiments using
      artificial phantom lesions and preliminary clinical experience.
AB  - PURPOSE: To conduct computed tomography (CT)-guided puncture exactly and safely,
      we newly developed a laser guiding puncture system that can be used in a
      commercially available CT scanner. MATERIALS AND METHODS: The laser-guided CT
      puncture system is built on the CT table with an aluminum frame. Preliminary
      simulation tests were conducted using two models representing the body and
      nodular lesions, and puncture procedures were carried out for 15 patients using
      this system. RESULTS: The mean distance and standard deviation from the center in
      simulation experiments conducted using this puncture system were 2.95 +/- 1.20 mm
      for operator A and 3.52 +/- 1.12 mm for operator B. There was no statistically
      significant difference between the operators (P = 0.40) or the angles (P = 0.32).
      For five lung biopsy patients, the distance from the target point planned before
      biopsy to the actual last puncture point was 0-8 mm. For 10 percutaneous
      vertebroplasty (PVP) patients (two performed in Th11, one in Th12, five in L1,
      two in L2), the plan before the puncture procedure was to pass the needle through
      the vertebral pedicle in all cases. The distance between the planned target point
      and the actual last puncture point was 0-5 mm. CONCLUSION: This system has the
      potential to accomplish the CT-guided puncture procedure safely and accurately.

PMID- 17514372
TI  - The three families of respiratory NADH dehydrogenases.
AB  - Most reducing equivalents extracted from foodstuffs during oxidative metabolism
      are fed into the respiratory chains of aerobic bacteria and mitochondria by
      NADH:quinone oxidoreductases. Three families of enzymes can perform this task and
      differ remarkably in their complexity and role in energy conversion. Alternative
      or NDH-2-type NADH dehydrogenases are simple one subunit flavoenzymes that
      completely dissipate the redox energy of the NADH/quinone couple. Sodium-pumping
      NADH dehydrogenases (Nqr) that are only found in procaryotes contain several
      flavins and are integral membrane protein complexes composed of six different
      subunits. Proton-pumping NADH dehydrogenases (NDH-1 or complex I) are highly
      complicated membrane protein complexes, composed of up to 45 different subunits,
      that are found in bacteria and mitochondria. This review gives an overview of the
      origin, structural and functional properties and physiological significance of
      these three types of NADH dehydrogenase.

PMID- 17514373
TI  - Influence of usage practices, ethnicity and climate on the skin compatibility of
      sanitary pads.
AB  - Modern disposable sanitary pads are becoming available worldwide. Regional
      differences in usage practices, ethnicity, and climate may influence their skin
      compatibility. Pad usage practices depend on culture, economics, and menstrual
      physiology. Daily usage is higher in Japan and but lower in Nigeria compared to
      North America or Western Europe. Evidence for ethnic differences in skin irritant
      susceptibility is not compelling. Dark skin may be less susceptible to certain
      irritants than fair skin; the Japanese may experience a higher degree of sensory
      irritation than Caucasians. Ambient conditions such as high temperature and
      humidity increase the skin temperature and skin surface moisture under sanitary
      pads by small but measurable amounts, causing no discernible skin irritation;
      vapor-permeable pad backings reduce these effects. Cold dry conditions, which can
      irritate exposed skin, may not affect vulvar skin to the same degree due to its
      elevated hydration and occlusion. To address the practical significance of these
      variables, results of prospective clinical trials of sanitary pads performed by
      industry and academic scientists in North America (Indiana), Mexico, Western
      Europe (Munich, Athens, Goteborg, Sweden), Eastern Europe (Kiev) and Africa
      (Abuja, Nigeria) were reviewed. Despite the diverse range of conditions, no
      significant adverse skin effects were observed with modern pads compared to
      traditional pad designs. Study participants generally preferred modern pads for
      performance and comfort.

PMID- 17514374
TI  - A dedicated ectopic pregnancy team leads to an improvement in patients'
      management.
AB  - INTRODUCTION: The aim of the study is to determine whether a dedicated ectopic
      pregnancy team improves the management of haemodynamically stable patients with
      suspected ectopic pregnancy who do not require immediate life-saving surgery.
      METHODS: A non-randomized population based study involving 210 patients admitted
      with a suspected ectopic pregnancy over a 2-year period in a university teaching
      hospital in the UK, was carried out to compare the management of those women
      before and after the introduction of the ectopic pregnancy team. RESULTS:
      Following the introduction of an ectopic pregnancy team, there were fewer
      laparotomies performed, fewer negative diagnostic laparoscopies, a reduced
      overall surgical intervention rate, and a reduced duration of hospital stay.
      Although, it was difficult to quantify the extent of improvement of training, yet
      there were fewer operations performed out-of-hours, more continuity of care, more
      learning opportunities and acquisition of laparoscopic skills of junior staff.
      CONCLUSIONS: The introduction of an ectopic pregnancy team led to an improvement
      in the management of patients with suspected ectopic pregnancies. Efforts aiming
      at setting up such a specialized team and its implementation in day-to-day
      clinical practice should be considered in hospitals where the mainstay of
      treatment remains laparotomy.

PMID- 17514375
TI  - Delay in treatment for psychosis : its relation to family history.
AB  - BACKGROUND: Recent evidence that treatment delay may compromise the potential for
      recovery from psychotic disorders has resulted in increased interest in factors
      that influence help seeking. In this paper, we test the hypotheses, derived from
      past research, that having a positive family history of a psychotic disorder in
      first or second degree relatives will be associated with a shorter duration of
      untreated psychosis (DUP), but a longer duration of untreated illness (DUI). Data
      were derived from 169 patients who presented for treatment to a first episode
      psychotic disorders program. Information was collected concerning family history,
      DUP, DUI and the timing of family recognition of the need for help. RESULTS: The
      findings failed to confirm a positive family history being associated with
      shorter DUP, but did support the prediction of such a history being related to
      longer DUI. Paradoxically, given the latter findings, families with a history of
      psychotic illness were more likely to recognize the need for help for the ill
      person prior to the onset of psychotic symptoms. The difference in DUI appears to
      reflect the presence of a longer period of early signs prior to the emergence of
      psychosis in those cases with a positive family history. CONCLUSIONS: These
      findings suggest the importance of examining family history as a possible
      confound of any relationship between DUI and long-term course of illness.

PMID- 17514376
TI  - Effect of pomegranate (Punica granatum) juice intake on hepatic oxidative stress.
AB  - Pomegranate juice (PJ) possesses a high antioxidant activity, which has been
      related to beneficial health properties. However, in vivo confirmation and
      characterization of these effects on biological systems are lacking and needed.
      This study was performed in order to investigate the effect of prolonged PJ
      ingestion on general oxidation status. For this purpose, mice ingested PJ (or
      water in control group) during four weeks, after which damage to lipids, proteins
      and DNA were evaluated as oxidative cell biomarkers. Levels of hepatic
      glutathione and the activities and expression of enzymes involved in its
      metabolism were determined. Catalase and SOD activities were quantified as these
      enzymes have a crucial role in antioxidant defence. Protection against protein
      and DNA oxidation was found in PJ group. There was also a significant decrease in
      GSH and GSSG, without change in the GSH/GSSG ratio. All studied enzymatic
      activities (GPx, GST, GR, SOD and catalase) were found to be decreased by PJ
      treatment. Additionally, RT-PCR results showed that GST and GS transcription were
      also decreased in this group. These results are compatible with a protective
      effect of PJ against systemic oxidative stress in mice.

PMID- 17514377
TI  - Development of a model for optimal food fortification: vitamin D among adults in
      Finland.
AB  - BACKGROUND: Average vitamin D intake is low in Finland. Even though almost all
      retail milk and margarine are fortified with vitamin D, the vitamin D intake is
      inadequate for a significant proportion of the population. Consequently, expanded
      food fortification with vitamin D would be motivated. However, there is a risk of
      unacceptably high intakes due to the rather narrow range of the adequate and safe
      intake. Therefore, a safe and efficient food fortification practice should be
      found for vitamin D. AIM OF THE STUDY: To develop a model for optimal food
      fortification and apply it to vitamin D. METHOD: The FINDIET 2002 Study (48-h
      recall and data on supplement use (n = 2007), and 3 + 3 days' food records, n =
      247) was used as the test data. The proportion of the population whose vitamin D
      intake is between the recommended intake (RI) and the upper tolerable intake
      level (UL) was plotted against the fortification level per energy for selected
      foods. The fortification level that maximized the proportion of the population
      falling between RI and UL was considered the optimal fortification level.
      RESULTS: If only milk, butter milk, yoghurt and margarine were fortified, it
      would be impossible to find a fortification level by which the intake of the
      whole population would lie within the RI-UL range. However, if all potentially
      fortifiable foods were fortified with vitamin D at level 1.2-1.5 microg/100 kcal,
      the intake of the whole adult population would be between the currently
      recommended intake of 7.5 microg/d and the current tolerable upper intake level
      of 50 microg/day (model 1). If the RI was set to 40 microg/day and UL to 250
      microg/day, the optimal fortification level would be 9.2 microg/100 kcal in the
      scenario where all potentially fortifiable foods were fortified (model 2). Also
      in this model the whole population would fall between the RI-UL range.
      CONCLUSIONS: Our model of adding a specific level of vitamin D/100 kcal to all
      potentially fortifiable foods (1.2-1.5 microg/100 kcal in model 1 and 9.2
      microg/100 kcal in model 2) seems to be an efficient and safe food fortification
      practise.

PMID- 17514378
TI  - Effects of pre- and postnatal protein deprivation on atrial natriuretic peptide-
      (ANP-) granules of the right auricular cardiocytes. An ultrastructural
      morphometric study.
AB  - BACKGROUND: The atrial natriuretic peptide (ANP) is a peptide hormone that is
      mainly produced in the cardiocytes of the atria and auricles, where it is stored
      within secretory granules. AIM OF THE STUDY: The aim of the present work was to
      analyze the effects of pre- and postnatal protein malnutrition on weight gain,
      the size of the heart and the number and sizes of the ANP-granules in the
      cardiocytes of the rat's right auricle. This study was conducted on 21-day-old
      rats from mothers exposed to 73% protein restriction during the gestation and
      lactation and on age-matched control animals. At this stage, both control and
      protein-deprived animals were killed by a lethal intraperitonial injection of
      sodic pentobarbital. The weight and the size of the heart were determined and ANP
      granules of auricular cardiocytes were examined by transmission electron
      microscopy and ultrastructural morphometry. RESULTS: Protein deprivation of the
      mother throughout pregnancy, and the mother and unweaned rat pups in the first 21
      postnatal days reduced the weights of pups to about 60% of the normally fed
      group. The weight and size of the heart were also reduced, by about 50%. Despite
      this, perinatal malnutrition did not significantly affect the numbers of ANP
      granules/field in the cardiocytes. However, there was a small but significant
      reduction in the sizes of granules. CONCLUSION: It is concluded that ANP-granules
      are protected from loss even when there is a substantial reduction in body weight
      and organ size caused by protein deprivation.

PMID- 17514379
TI  - Genetic characterization of avian malaria (Protozoa) in the endangered lesser
      kestrel, Falco naumanni.
AB  - We genetically analyzed avian malaria (Protozoa) isolated from lesser kestrels
      (Falco naumanni) breeding in La Mancha, Central Spain. A total of 586 adult
      individuals were screened for blood parasites using a very efficient polymerase
      chain reaction approach that amplifies a partial segment (498 bp) of the
      cytochrome b gene of avian malaria of the genera Haemoproteus and Plasmodium. The
      prevalence of Plasmodium was 8.2%, and the prevalence of Haemoproteus was 4.1%.
      Sequence analyses revealed six unique lineages of avian malaria, three Plasmodium
      (LK5, LK6, RTSR1) and three Haemoproteus (LK2, LK3, LK4). According to sequence
      divergence, these lineages seem to correspond to at least three different
      species, although all recovered lineages could be independent evolutionary units.
      The third most common lineage (RTSR1) has been previously retrieved from two
      other avian host species, including a resident African bird species and a trans
      Saharan migrant passerine, suggesting that lesser kestrels could acquire this
      Plasmodium lineage at their winter quarters in Africa.

PMID- 17514380
TI  - An evaluation of primers amplifying DNA targets for the detection of
      Cryptosporidium spp. using C. parvum HNJ-1 Japanese isolate in water samples.
AB  - The performance of polymerase chain reaction (PCR) procedures for the detection
      of Cryptosporidium parvum HNJ-1 strain (genotype II) oocysts purified from mice
      using published protocols was evaluated. Oocysts were concentrated from fecal
      samples of infected severe combined immunodeficiency (SCID) mice by sucrose
      flotation and were then purified by immunomagnetic separation method. The
      genotype of C. parvum was established as type II by restriction fragment length
      polymorphism (RFLP) analysis. Water samples were spiked with different numbers of
      oocysts, determined by limiting dilution. Genomic DNA was extracted and used for
      PCR assays targeting various Cryptosporidium species genes (Beta-Tubulin, COWP,
      70 kDa HSP, SSU rRNA, ITS1, TRAP-C1 and TRAP-C2 gene). DNA from oocyst numbers of
      more than 1 x 10(4) was detected using each of the primers. However, when using
      lower oocyst numbers, the tools based on 9 of the 16 different primer assays gave
      sufficient results. Assays using the remaining seven primers gave less than
      satisfactory results. A new primer set, named VKSS-F1/2 and VKSS-R1/2, that
      target the 18 SSU rRNA gene of C. parvum was constructed and applied. The VKSS
      F1/2 and VKSS-R1/2 assays amplified DNA isolated from spiked samples in 206 of
      211 trials (97.6%). This illustrates the difficulty of detecting low numbers of
      Cryptosporidium spp. oocysts by molecular methods when working with environmental
      samples.

PMID- 17514381
TI  - Revisited ITS2 phylogeny of Anopheles (Anopheles) Hyrcanus group mosquitoes:
      reexamination of unidentified and misidentified ITS2 sequences.
AB  - The Anopheles (Anopheles) Hyrcanus group of mosquitoes is very important for
      human health because some are malarial vector mosquitoes. Despite their
      pathological importance, some unidentified internal transcribed spacer 2 (ITS2)
      sequences have been reported from members of this group, and their phylogenetic
      relationships have been rarely understood. In the present study, 84 ITS2
      sequences for the Hyrcanus group members were retrieved from GenBank. The
      detailed sequence comparison unambiguously revealed that the unknown1 sequences
      of Li et al. (Zootaxa 939:1-8, 2005), YM-2004 (or sp.2) of Ma and Xu [J Med
      Entomol 42(4):610-619, 2005], Anopheles sp. of Ree et al. (2005), and Anopheles
      lesteri reported by Gao et al. [J Med Entomol 41(1):5-11, 2004] are identical to
      Anopheles belenrae [Rueda (Zootaxa 941:1-26, 2005)] and that YM-2003 (or sp.1) of
      Ma and Xu [J Med Entomol 42(4):610-619, 2005] is closely related to A. lesteri.
      In addition, some candidate species that may be synonymized are suggested in
      addition to the possibility that A. lesteri may be divided into at least three
      types: A, B, and C. The neighbor joining, maximum parsimony, and maximum
      likelihood trees show that the 23 examined Hyrcanus group members could be
      divided into four subgroups. The phylogenetic relationships among them are
      generally well resolved with high bootstrapping values (60-100%), and they are
      consistently supported by all three trees without any conflicts. These results
      may strongly suggest that the morphology-based groupings of the Hyrcanus group
      members should be seriously reconsidered. Further study must be conducted to
      address the following issues: the three or more multitypified A. lesteri; the
      unidentified YM-2003 closely related to A. lesteri; and the synonymies of
      Anopheles peditaeniatus/Anopheles nigerrimus, Anopheles kunmingensis/Anopheles
      liangshanensis, Anopheles pullus/Anopheles junlianensis, and Anopheles
      engarensis/Anopheles kleini.

PMID- 17514382
TI  - Is patients' preferred involvement in health decisions related to outcomes for
      patients with HIV?
AB  - BACKGROUND: Previous studies suggest that patients who are more involved in their
      medical care have better outcomes. OBJECTIVES: We sought to compare health care
      processes and outcomes for patients with HIV based on their preferred level of
      involvement in health decisions. DESIGN: Cross-sectional analysis of audio
      computer-assisted interviews with patients at an urban HIV clinic. PATIENTS: One
      thousand and twenty-seven patients awaiting an appointment with their primary
      care provider. MEASURES: Patients were asked how they preferred to be involved in
      decisions (doctor makes most or all decisions, doctor and patient share
      decisions, patient makes all decisions). We also asked patients to rate the
      quality of communication with their HIV provider, and their self-reported receipt
      of and adherence to HAART. RESULTS: Overall, 23% patients preferred that their
      doctor make all or most decisions, 63% preferred to share decisions with their
      doctor, and 13% preferred to make all final decisions alone. Compared to patients
      who prefer to share decisions with their HIV provider, patients who prefer that
      their provider make all/most decisions were significantly less likely to adhere
      to HAART (OR [odds ratio] 0.57, 95% CI 0.38-0.86) and patients who preferred to
      make decisions alone were significantly less likely to receive HAART or to have
      undetectable HIV RNA in unadjusted analyses (OR 0.52, 95% CI 0.31-0.87 for
      receipt of HAART; OR 0.64, 95% CI 0.44-0.95 for undetectable HIV RNA). After
      controlling for potentially confounding patient characteristics and differences
      in patient ratings of communication quality, patients who preferred that their
      provider make all/most decisions remained significantly less likely to adhere to
      HAART (OR 0.58, 95% CI 0.38-0.89); however, the associations with receipt of
      HAART and undetectable HIV RNA were no longer significant (OR 0.60, 95% CI 0.34
      1.05 for receipt of HAART; OR 0.80, 95% C.I 0.53-1.20 for undetectable HIV RNA).
      CONCLUSIONS: Although previous research suggests that more patient involvement in
      health care decisions is better, this benefit may be reduced when the patient
      wants to make decisions alone. Future research should explore the extent to which
      this preference is modifiable so as to improve outcomes.

PMID- 17514383
TI  - Hepatic resections by means of electrothermal bipolar vessel device (EBVS)
      LigaSure V: early experience.
AB  - BACKGROUND: Many techniques and devices are available for performing liver
      resection, such as clamp crushing, Cavitron Ultrasonic Surgical Aspirator (CUSA),
      Hydrojet and dissecting sealer, ultrasonic shears, and, more recently,
      electrothermal bipolar vessel sealing system (EBVS). In this prospective trial we
      sought to evaluate the impact of EBVS on hepatic resections. METHODS: From March
      2004 to December 2005, 24 patients from our consecutive liver resection series
      were enrolled in the present study. There were 17 males and 7 females with a mean
      age of 59.6 years (range = 41-80) who had colonic cancer metastases (18),
      hepatocarcinoma (3), angioma (2), and intrahepatic lithisasis (1). Patients were
      prospectively randomized to undergo liver resection via EBVS LigaSure V (12
      patients, group A) or ultrasonic shears harmonic scalpel (HS) (12 patients, group
      B). Hepatic procedures did not differ significantly between the two groups and
      were as follows: right hepatectomy (2), left hepatectomy (1), bisegmentectomy
      (14), and segmentectomy (7). RESULTS: There was no mortality in either group. The
      mean operative time was 136.7 min (range = 90-210) in group A and 187.9 min
      (range = 130-360) in group B. The Pringle maneuver was done in five patients in
      group A [mean time = 11.4 min (range = 6-12)] and in four patients in group B
      [mean time = 16 min (range = 9-26)]. The mean blood loss, total bile salts, and
      hemoglobin concentration from drained fluid on the second postoperative day were
      205.8 vs. 506.7 ml, 0.6 vs. 1.1 mmol/L, and 1.0 vs. 2.1 g/L (p < 0.05) for groups
      A and B, respectively. Mean postoperative hospital stay was 6.1 vs. 7.8 days. In
      group B a patient who underwent right hepatectomy for colon cancer metastases had
      transient hepatic failure. No patients received blood transfusions in group A,
      while two or more blood units were administered in two cases in group B.
      CONCLUSIONS: In the present study EBVS proved to be safe and effective for liver
      resection. By means of this device, statistically significant benefits concerning
      blood loss, total bile salts, and hemoglobin postoperative leakage were found.

PMID- 17514384
TI  - The least invasive name wins: reply to Paluch, T (2006) Maximally accurate
      nomenclature. Surg Endosc [Epub ahead of print].

PMID- 17514385
TI  - Combined thoracoscopic and endoscopic management of mid-esophageal benign
      lesions: use of the prone patient position : Thoracoscopic surgery for mid
      esophageal benign tumors and diverticula.
AB  - BACKGROUND: Both benign tumors and mid-esophageal diverticula are rare
      conditions; underlying disorders may be present in case of diverticula.
      Traditionally, thoracotomy was the preferred route to approach these lesions.
      Now, more surgeons are using minimally invasive techniques to treat these benign
      mid-esophageal lesions. PATIENTS AND METHODS: A total of 12 patients with
      symptomatic mid-esophageal lesions were studied, benign tumors were seven cases
      and five cases of diverticula. We present our experiences with thoracoscopic
      enucleation of benign tumors and diverticulectomy aided by peroperative
      endoscopy. All the patients were placed in the prone position and approached via
      a right thoracotomy. RESULTS: Two patients had minor complications of pneumonitis
      and dysphagia, which were treated conservatively. One patient had a leak from the
      staple line that needed a second-look thoracoscopy and evacuation of abscess.
      DISCUSSION: In this study, we highlight the use of the prone patient position,
      the advantages of a right thoracoscopic approach and the value of peroperative
      endoscopy. The prone position was first described in 1994, but has not been
      popular. Peroperative endoscopy accurately localizes diverticula and determines
      level of stapler application. CONCLUSION: Thoracoscopy has definite benefits
      regarding reduced morbidity. The combined modality of peroperative endoscopy is
      useful in diverticulectomy. Based on our experience, we believe the prone patient
      position is the ideal position for esophageal surgery.

PMID- 17514386
TI  - Wound infection after elective laparoscopic surgery for colorectal carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate various clinical parameters
      that would influence the occurrence of wound infection (WI) in elective
      laparoscopic surgery (LS) for colorectal carcinoma. METHODS: The study included
      290 patients who underwent LS between June 2001 and December 2005. WI was
      diagnosed within 30 days of the operation, and both superficial and deep incision
      surgical site infection were evaluated together. RESULTS: Eighteen (6.2%) were
      diagnosed with WI. Of the infected patients, nine (50%) had WI at the extraction
      site, six (33%) at the port site of the drainage tube, and three (17%) at the
      supraumbilical incision. Following bivariate analysis, the variables of stoma
      creation, intraoperative hypotension, and length of operation were selected for
      multivariate analysis as their P values were <0.2, the predominant cutoff, and
      stoma creation and intraoperative hypotension were independently predictive of
      developing WI. Regarding the duration of postoperative hospital stay, there was
      no significant difference between patients with or without WI. CONCLUSIONS: Stoma
      creation and intraoperative hypotension were independent risk factors for WI. The
      results obtained in this study should be considered in an effort to prevent WI in
      LS for colorectal carcinoma, although these risk factors need further evaluation.

PMID- 17514387
TI  - Laparoscopic repair of inguinal hernias using an intraperitoneal onlay mesh
      technique and a Parietex composite mesh fixed with fibrin glue (Tissucol).
      Personal technique and preliminary results.
AB  - INTRODUCTION: Laparoscopic repair of inguinal hernias is usually achieved by
      totally extraperitoneal (TEP) or transabdominal preperitoneal (TAPP) techniques.
      The intraperitoneal onlay mesh (IPOM) could be an interesting alternative as it
      is much easier to perform and faster to execute. This technique is subject to
      correct selection of indications and to demonstration of its safety. MATERIALS
      AND METHODS: From January 2003 to January 2006 we performed 61 laparoscopic
      hernia procedures on 60 selected patients (60 males with a mean age of 60 and
      mean weight of 76 kg) with an IPOM technique combining the Parietex composite
      mesh (12 cm circular model) and a fibrin glue (Tissucol) for its fixation. The
      glue was diluted to increase fixation time and applied to the mesh prior to
      positioning on the hernia defect. RESULTS: Mean operative time was 10 minutes.
      Mean hernia diameter was 2.5 cm (+/- 0.8 cm). 10 hernias were direct, 51 were
      indirect and 10 out of 61 were recurrent. We did not convert any of the
      laparoscopic procedures. Mean hospital stay was one day; mean recovery time for
      working and general physical activities was five days. Patients were checked
      after one week, 1-3-6 months and 1-2 years. Average follow up time was 23.7
      months. 1.6 % of patients showed short-term complications: one trocar site
      haematoma. No additional complications were reported; particularly, we had no
      recurrence, no seroma, no mesh migration, and no bowel obstruction or fistula.
      CONCLUSION: Results of this study show intraperitoneal (IP) tolerance to this
      kind of mesh and the safety of its fixation with Tissucol. The absence of
      recurrence and complications could be a good reason to extend the indication of
      IPOM hernia repair. However, these preliminary results should be confirmed by
      longer follow-up.

PMID- 17514388
TI  - Post-procedural (immediate and delayed) bleeding rate.

PMID- 17514389
TI  - Long-term follow-up of endoscopic stenting in patients with chronic pancreatitis
      secondary to pancreas divisum.
AB  - BACKGROUND: Pancreas divisum is the most common anatomic variant of pancreatic
      development and may lead to pancreatitis. This study evaluated the efficacy of
      endoscopic stenting in patients with chronic pancreatitis due to pancreas
      divisum. METHODS: Between 1993 and 2005, 32 patients with chronic pancreatitis
      due to pancreas divisum were treated with endoscopic stenting. Each patient
      underwent an endoscopic retrograde cholangiopancreatography to confirm the
      diagnosis of pancreas divisum prior to endoscopic stenting. A survey was
      conducted by telephone conversation to evaluate pain intensity, symptom relief,
      hospital admissions, quality of life and pain medication usage, which was
      verified by a statewide narcotic electronic database. Eight of the 32 patients
      were unavailable for the interview and were not included in the analysis of the
      study. Results are expressed as mean +/- standard error of the mean (SEM).
      RESULTS: Twenty-four patients were followed up for a period of 59.6 months. The
      overall pain level average in the 24 patients decreased significantly from 8.9 +/
      0.4 pre-stenting to 3.9 +/- 0.7 post-stenting (P < 0.05) on a scale of 1 to 10.
      The number of hospital admissions per year in these patients decreased
      significantly from 7.3 +/- 2.1 pre-stenting to 2.1 +/- 0.4 post-stenting (P <
      0.05). Pain medication usage reported by the patients found a decrease in 58% of
      patients, 21% remained the same, and 13% increased their usage. There was
      improvement in nausea (67%), vomiting (63%), and chronic pain (75%). Thirteen
      patients (55%) were treated endoscopically without requiring surgery and 11 (45%)
      patients required surgery after stenting. These 11 patients had surgery an
      average of 25 months post-stenting. The complication rate of post-procedural
      pancreatitis was 3.4%. No mortality was reported in this study. CONCLUSION:
      Endoscopic stenting of the pancreatic duct is a safe and effective first
      treatment for patients with pancreatitis secondary to pancreas divisum. Surgery,
      when performed for endoscopic stenting failure, is effective as an adjunctive
      treatment.

PMID- 17514390
TI  - Recent in vivo surgical robot and mechanism developments.
AB  - The surgical landscape is quickly changing because of the major driving force of
      robotics. Well-established technology that provides robotic assistance from
      outside the patient may soon give way to alternative approaches that place the
      robotic mechanisms inside the patient, whether through traditional laparoscopic
      ports or through other, natural orifices. While some of this technology is still
      being developed, other concepts are being evaluated through clinical trials. This
      article examines the state of the art in surgical robots and mechanisms by
      providing an overview of the ex vivo robotic systems that are commercially
      available to in vivo mechanisms, and robotic assistants that are being tested in
      animal models.

PMID- 17514391
TI  - Pediatric ERCP in a multidisciplinary community setting: experience with a
      fellowship-trained general surgeon.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) has been used to evaluate
      and treat pancreaticobiliary disorders and trauma in the pediatric population.
      Still representing a small percentage of total pediatric endoscopies, this
      procedure has been performed most commonly by a small subset of adult and
      pediatric gastroenterologists at quaternary referral centers. METHODS: In this
      study, we present a review of one fellowship-trained general surgeon's experience
      with pediatric ERCP in a teaching community pediatric hospital for the purpose of
      comparison with national series. RESULTS: All ERCPs performed by one general
      surgeon as part of a multidisciplinary team over a 5-year period in patients aged
      16 years or less were reviewed. Success and complication rates were compared
      between our series and published pediatric and adult series using Fisher's exact
      test. Comparisons were made of indications, type of anesthesia, final diagnosis,
      and therapeutic interventions to ensure similar study populations. A total of 26
      ERCPs were performed in 19 patients ranging from 7 to 16 years old. Therapeutic
      procedures included sphincterotomy (11), stent placement (7), stone removal (3),
      and dilation (2). In one case, stone removal and stent placement were performed
      in conjunction with pancreatic lithotripsy. In two cases the involved duct was
      not visualized. There were no instances of pancreatitis, bleeding, or perforation
      related to ERCP. CONCLUSIONS: When compared with published series, our data
      demonstrated no significant difference in success or complication rates. Our
      study demonstrates that pediatric ERCP can be performed by fellowship-trained
      general surgeons with success and complication rates comparable to accepted
      standards. Integration of the ERCP-trained general surgeon into the pediatric
      team is a potential asset in the care of pediatric patients with
      pancreaticobiliary disorders.

PMID- 17514392
TI  - Laparoscopic treatment of blunt splenic injuries: initial experience with 11
      patients.

PMID- 17514393
TI  - Exploring new technologies to facilitate laparoscopic surgery: creating
      intestinal anastomoses without sutures or staples, using a radio-frequency-energy
      driven bipolar fusion device.
AB  - INTRODUCTION: Intestinal anastomotic healing requires apposition of the collagen
      containing submucosal layers of the opposing intestinal walls, which is
      traditionally achieved by staples or sutures. Recently, a feedback-controlled
      bipolar sealing system (LigaSure) has been successfully introduced to seal and
      transect vessels. Since this technology depends on fusion of collagen fibres
      which are abundantly present in the intestinal wall, the possibility to create
      intestinal anastomoses using this technology was investigated in the present
      study. MATERIALS AND METHODS: For this purpose a new-generation radiofrequency
      (RF) generator and a prototype of the Ligasure Anastomotic Device (LAD) have been
      developed. The generator incorporates a closed loop control system which monitors
      tissue fusion, compares it with a mathematical model of ideal fusion based on the
      density and compliance of intestinal tissue and adjusts energy output
      accordingly. In total 8 anastomoses were created in a porcine model (4 pigs, 2
      anastomoses each) and healing was assessed by macroscopic and histological
      examination. RESULTS: All seals were macroscopic intact both immediate after
      creation and at sacrifice at the 7th postoperative day. Between operations, pigs
      appeared healthy and had normal intestinal passage. Histological examination of
      the anastomoses revealed undisturbed healing with granulation tissue, newly
      synthesised collagen in the submucosa and re-epithelialization at the borders of
      the seals. CONCLUSION: These results confirm the feasibility to create
      experimental intestinal anastomoses using LigaSure technology. This may be an
      important step towards the development of new laparoscopic equipment combining
      dissecting and reconstructive properties within one single instrument.

PMID- 17514394
TI  - Anterior fundoplication decreases esophageal clearance in patients undergoing
      Heller myotomy for achalasia.
AB  - BACKGROUND: Anterior fundoplication (AF) following laparoscopic Heller myotomy
      (LHM) for achalasia may prevent esophageal leaks and gastroesophageal reflux but
      cause dysphagia. Our study attempts to determine the effect of AF on esophageal
      leaks, nuclear medicine esophageal clearance (EC), symptom frequency (SF), and
      Van Trappen symptom scores (SS) for dysphagia, regurgitation, and heartburn.
      METHODS: Between 1995 and 2004, pre- and postoperative (2-12 months) EC, SF, and
      SS scores were compared in 95 patients undergoing LHM for achalasia with AF (n =
      71) and without (n = 24) AF. RESULTS: There were no leaks or deaths. Laparoscopic
      Heller myotomy decreased the frequency of postoperative dysphagia, regurgitation,
      and heartburn with AF (96% preoperation versus 6% postoperation, 94% versus 3%,
      58% versus 6%) (p = 0.001) and without AF (100% versus 0%, 83% versus 0%, 50%
      versus 4%) (p = 0.001). Laparoscopic Heller myotomy improved all SS in both
      groups. There was no difference between postoperative dysphagia (1.38 +/- 0.64
      versus 1.17 +/- 38) p = 0.06, regurgitation (1.17 +/- 51 versus 1.04 +/- 0.20) p
      = 0.08, and heartburn (1.29 +/- 62 versus 1.53 +/- 0.80) p = 0.185 scores between
      the AF and no-AF group, respectively. There is a trend toward improvement in
      dysphagia and regurgitation in the no-AF group. Laparoscopic Heller myotomy
      improved EC in the supine and upright positions in both groups of patients (p =
      0.001). There was an improved mean change in EC (10 min upright) in the no-AF
      group versus the AF group (50.7% +/- 30.8 versus 29.7% +/- 30.2) p = 0.004.
      CONCLUSIONS: Laparoscopic Heller myotomy improves esophageal transit and the
      frequency and severity of dysphagia, heartburn, and regurgitation in a safe
      manner. Patients without AF show a statistically better upright EC with a trend
      toward improved dysphagia and regurgitation.

PMID- 17514395
TI  - The importance of classification in sympathetic surgery and a proposed mechanism
      for compensatory hyperhidrosis: experience with 464 cases.

PMID- 17514396
TI  - Laparoscopic herniorrhaphy after manual reduction of incarcerated inguinal
      hernia.
AB  - BACKGROUND: After a manual reduction (MR) of an incarcerated inguinal hernia
      (IIH), it is recommended that an open herniotomy (OH) be performed after a one
      day delay because of the postincarceration tissue edema. We assumed that
      performing laparoscopic herniorrhaphy (LH) shortly after MR reduces the hospital
      stay for IIH. We compared LH with OH retrospectively. We expected equal results
      but a shorter hospital stay with LH. METHODS: From May 2002 to April 2006, 40
      successive patients with IIH were admitted. OH was scheduled two days after MR,
      whereas no delay for performing LH was required. Patients in whom MR failed and
      who required immediate surgery (n = 4) and patients whose medical condition
      prevented surgery within the schedule (n = 3) were excluded from the study.
      Follow-up consisted of an outpatient visit and telephone survey. RESULTS: Thirty
      three patients (31 male, 15 OH, 18 LH) were included. For the LH patients, the
      median age was 15 (0.7-81) months and that for OH patients was 8.6 (0.6-61)
      months. For LH patients, weight = 11.5 (3.6-22) kg and for OH patients, weight =
      9.8 (3.5-17) kg (p = NS). Median delay from MR to OH was 2 (2-4) days, and from
      MR to LH median delay was 1 (0-3) day (p < 0.05). Length of the operation was 29
      (10-80) min in OH and 39 (20-60) min in LH (p = NS). Total theatre time was 44
      (17-111) min in OH and 66 (44-86) min in LH (p < 0.05), and hospital time was 3
      (3-6) days in OH and 2 (1-4) days in LH (p < 0.05). Median cost (surgery +
      hospitalization) of OH was euro 2315 (1910-3530) and that of LH was euro 3215
      (2605-3650) (p < 0.05). Median follow-up was 26 (4-49) months, one patient (LH)
      had re-LH for recurrent hernia. CONCLUSION: After MR, LH can be performed with
      minimal delay and similar results as OH. Despite increased theatre time and total
      hospital costs, LH shortened hospital stay.

PMID- 17514397
TI  - Bile duct injuries during laparoscopic cholecystectomy: primary and long-term
      results from a single institution.
AB  - BACKGROUND: Iatrogenic bile duct injury carries high morbidity. After the
      introduction of laparoscopic cholecystectomy the incidence of these injuries has
      at least doubled, and even after the learning curve, the incidence has plateaued
      at the level of 0.5%. METHODS: A total of 32 patients sustained biliary tract
      injuries of the 3736 laparoscopic cholecystectomies performed in and around Turku
      University Central Hospital between January 1995 and April 2002. The data
      concerning primary treatment and long-term results were collected and analyzed
      retrospectively. RESULTS: The overall incidence for bile duct injuries, including
      all the minor injuries (cystic duct leaks and bile duct strictures), was 0.86%;
      for major injuries alone the incidence was 0.38%. Nineteen percent of the
      injuries were detected intraoperatively. All the cystic duct leaks were treated
      endoscopically with a 90% success rate. Of the bile duct strictures 88% were
      treated successfully with endoscopic techniques. Ninety-three percent of the
      major injuries, including tangential lesions of common bile duct and total
      transections, were treated operatively. The operation of choice was either
      hepaticojejunostomy or cholangiojejunostomy in 69% of the cases; the rest were
      treated with simple suturing over a T-tube or an endoscopically placed stent. The
      long-term results, with a median follow-up period of 7.5 years, are good in 79%
      of the operated patients and in 84% of the whole study population. Mortality rate
      was 3% and acute or chronic cholangitis was seen in 13% of the patients during
      follow-up. CONCLUSION: Most of the minor bile duct injuries, including cystic
      duct leaks and bile duct strictures, are well treatable with endoscopic
      techniques, whereas most of the major injuries require operative treatment, which
      at optimal circumstances gives good results.

PMID- 17514398
TI  - The utility of routine postoperative upper GI series following laparoscopic
      gastric bypass.
AB  - BACKGROUND: Routine upper gastrointestinal (UGI) studies following laparoscopic
      Roux-en-Y gastric bypass (LRYGBP) have the potential advantage of early
      identification of anastomotic complications. The aim of our study was to evaluate
      the efficacy of routine postoperative UGI and its relationship to clinical
      outcomes. METHODS: Over a three-year period, 516 patients underwent LRYGBP
      followed by routine postoperative UGI studies. Data were collected on the results
      of the UGI, clinical parameters, and patient outcomes. Study groups were composed
      of patients with a normal UGI (Group I, n = 455), abnormal UGI not requiring
      further intervention (Group II, n = 36), and abnormal UGI requiring further
      intervention (Group III, n =25). Statistical significance was set at alpha= 0.05
      level for all analyses. RESULTS: The three study groups were not statistically
      different in mean age (42 years) or body mass index (BMI) (45) and were
      predominantly female (90%). Most patients had an uneventful postoperative course.
      Anastomotic complications (gastrojejunostomy and jejunojejunostomy) were uncommon
      (1.3%). The sensitivity of the UGI for anastomotic leak in this study was low
      (33%). However, all patients with alimentary limb obstruction (n = 3) had UGI
      evidence of this complication. Of the 516 UGI reports, there were only 25 (4.8%,
      Group III) that were abnormal and required some form of intervention ranging from
      serial imaging (84%) to reoperation (16%). Of the various clinical parameters
      examined, the patients in Group III demonstrated a significantly higher
      prevalence of fever (p < 0.001), tachycardia (p < 0.01), vomiting (p < 0.001),
      and postoperative day 1 leukocytosis (p < 0.005). CONCLUSIONS: Our data suggest
      that routine UGI after LRYGBP has limited utility as it may result in unnecessary
      intervention based on false-positive results or a delay in treatment based on
      false-negative results. We advocate selective UGI imaging following LRYGBP based
      on the patient's clinical factors, particularly fever and tachycardia.

PMID- 17514399
TI  - Health economic evaluation of therapeutic strategies in patients with idiopathic
      achalasia: results of a randomized trial comparing pneumatic dilatation with
      laparoscopic cardiomyotomy.
AB  - BACKGROUND: We have prospectively collected information concerning the costs
      incurred during the management of patients allocated to either forceful
      dilatation or to an immediate laparoscopic operation because of newly diagnosed
      achalasia. METHODS: Fifty-one patients with newly diagnosed achalasia were
      randomized to either pneumatic dilatation to a diameter of 30-40 mm or to a
      laparoscopic myotomy to which was added a posterior partial fundoplication.
      Follow-ups were scheduled at 1, 3, 6, and 12 months after inclusion. At each
      follow-up visit a study nurse interviewed the patients regarding symptoms and
      their quality of life (QoL) and a health economic questionnaire was completed. In
      the latter questionnaire, patients were asked to report the presence and
      character of contacts with the healthcare system since the last visit. RESULTS:
      In the dilatation group six patients (23%), including the patient who was
      operated on because of perforation, were classified as failures during the first
      12 months of follow-up compared to one (4%) in the myotomy group (p = 0.047).
      Five of those classified as failures in the dilatation group subsequently had a
      surgical myotomy and the sixth patient was treated with repeated dilatations. The
      patient classified as failure in the myotomy group was treated with endoscopic
      dilatation. The initial treatment cost and the total costs were significantly
      higher for laparoscopic myotomy compared to a pneumatic dilatation-based strategy
      (p = 0.0002 and p = 0.0019, respectively). When the total costs were subdivided
      into the different resources used, we found that the single largest cost item for
      pneumatic dilatation was that for hospital stay and that for laparoscopic myotomy
      was the actual operative treatment (operating room time). The cost-effectiveness
      analysis, relating to the actual treatment failures, revealed that the cost to
      avoid one treatment failure (incremental cost-effectiveness ratio) amounted to
      9239 euros. CONCLUSION: The current prospective, controlled clinical trial shows
      that despite a higher level of clinical efficacy of laparoscopic myotomy to
      prevent treatment failure in newly diagnosed achalasia, the cost effectiveness of
      pneumatic dilatation is superior, at least when a reasonable time horizon is
      applied.

PMID- 17514400
TI  - Midterm outcome of radiofrequency thermal ablation for symptomatic uterine
      myomas.
AB  - BACKGROUND: Over the past decade an increasing demand for uterine-sparing
      treatment to manage symptomatic uterine myomas has become apparent in women's
      health care. A preliminary report showed that radiofrequency ablation (RFA) of
      uterine fibroids under laparoscopic guidance was a safe and effective minimally
      invasive approach with encouraging short-term results. The purpose of this study
      was to evaluate the midterm outcomes of radiofrequency ablation (RFA) of uterine
      myomas in terms of durability of symptom control and level of health-related
      quality of life. METHODS: Consecutive women with symptomatic uterine myomas, no
      plans for future pregnancy, and who declined hysterectomy were offered RFA
      ablation of uterine fibroids under laparoscopic guidance. Only 25 patients who
      completed at least the one-year follow-up assessment were included in the study
      group. Follow-up evaluations were scheduled at 1, 3, 6, 9, and 12 months and
      thereafter annually following the procedure. Improvement in myoma-related
      symptoms and impact on quality of life were assessed using a validated
      questionnaire (UFS-QOL). RESULTS: The median number of myomas treated per patient
      was 1 (range = 1-3). The median baseline volume of the dominant myoma was 76.8
      cm3 (range = 14.8-332.8). No intraoperative or postoperative complications
      occurred. The median follow-up time was 24 months, with nine women completing
      three years of follow-up. The median reduction in myoma volume was 68.8% and
      77.9% at six months and one year, respectively. No further change in fibroid size
      was observed at two years and three years. One year after the procedure, one
      woman (4%) underwent hysterectomy for recurrence of fibroid-related symptoms.
      Quality-of-life measures showed significant and durable improvement compared with
      baseline. CONCLUSIONS: RFA of symptomatic fibroids seems a valuable alternative
      to major surgery, with durable symptom relief for most patients and a low chance
      of recurrence at midterm.

PMID- 17514401
TI  - Laparoscopic primary choledochorrhaphy over endonasobiliary drainage tubes.
AB  - BACKGROUND: The T-tube is widely used in laparoscopic choledochotomy to
      decompress the biliary tree. However, there are high morbidity rates related to
      the T-tube. This study reviewed the results of laparoscopic primary
      choledochorrhaphy over endonasobiliary drainage (ENBD) tubes to find an effective
      alternative to the T-tube for the performance of laparoscopic choledochotomy.
      METHODS: From March 2003 to September 2005, 23 patients (9 men and 14 women) with
      choledocholithiasis underwent laparoscopic choledochotomy over ENBD tubes. The
      mean age of these patients was 47 years (range, 32-73 years). At admission, six
      patients had cholangitis. All the patients had ENBD tubes placed preoperatively
      after the failure of endoscopic sphincterotomy. RESULTS: There was no conversion
      to open surgery. The mean operative time was 90 min (range, 70-150 min). There
      were no biliary complications such as bile leaks, biliary peritonitis, or
      pancreatitis. No residual stones were found by postoperative cholangiograms. The
      ENBD tubes were removed between postoperative days 7 and 9. The hospital stay
      ranged from 8 to 14 days, with 16 patients (70%) discharged on postoperative day
      8. The complications were limited to one umbilical infection and one case of
      pneumonia. The median follow-up period was 24 months (range, 8-36 months), and
      none of the patients were readmitted with biliary symptoms. CONCLUSION:
      Laparoscopic choledochotomy over ENBD tubes proved to be technically feasible and
      safe. The ENBD tube decompresses the biliary tree and allows for cholangiography
      after surgery. Its removal does not need to wait for tract maturation, which
      allows an earlier removal of the tube and a shorter postoperative hospital stay.
      Laparoscopic choledochotomy over ENBD tubes is an effective alternative to the T
      tube in laparoscopic choledochotomy.

PMID- 17514402
TI  - Laparoscopic restaging of borderline ovarian tumors.
AB  - BACKGROUND: This study aimed to evaluate the feasibility and relevance of
      laparoscopic restaging surgery for women with borderline ovarian tumors. METHODS:
      From March 2001 to February 2006, 42 women referred for borderline ovarian tumors
      after laparoscopy or laparotomy underwent a laparoscopic restaging operation. Of
      these women, 37 (88%) had undergone conservative surgery including unilateral
      cystectomy (n = 16), bilateral cystectomy (n = 1), and unilateral salpingo
      oophorectomy (n = 20). The remaining five women (12%) had undergone radical
      surgery, including bilateral salpingo-oophorectomy (BSO) (n = 4) and hysterectomy
      with BSO (n = 1). Intraoperative rupture occurred in 13 cases. RESULTS: All 42
      restaging operations were performed via the laparoscopic approach. There were no
      intraoperative complications, no laparoconversions, and no postoperative
      complications. Laparoscopic restaging identified two persistent borderline
      ovarian tumors (12%) in women who had initially undergone cystectomy. Seven women
      were upstaged (16.6%) because of positive cytology (n = 2), peritoneal biopsy (n
      = 2), or omentum (n = 3). Among the 28 women with initial Federation
      International of Gynaecology and Obstetrics (FIGO) stage Ia disease, the final
      stage was Ia for 24 women, Ib for 2 women, IIIa for 1 woman, and IIIc for 1
      woman. Among the 12 women with initial stage Ic disease, 11 kept the same stage
      and 1 was upstaged to IIIc. The woman with initial stage IIa disease was upstaged
      to IIb, and the woman with initial stage IIc disease was upstaged to IIIc. The
      risk of upstaging was significantly higher among women with serous borderline
      tumors. Upstaging occurred in women with both initial stages I and II disease.
      CONCLUSIONS: The results confirm the feasibility and safety of laparoscopic
      restaging operations for women with borderline ovarian tumors. Cystectomy was
      associated with a risk of persistent lesions. The risk of upstaging was higher
      for women with serous borderline ovarian tumors and women with initial FIGO stage
      I or II disease.

PMID- 17514403
TI  - Marginal ulceration after laparoscopic gastric bypass: an analysis of
      predisposing factors in 260 patients.
AB  - BACKGROUND: Marginal ulceration after Roux-en-Y gastric bypass (RYGB) is
      diagnosed in 1% to 16% of patients. The factors predisposing patients to marginal
      ulceration are still unclear. METHODS: A total of 260 patients who underwent
      laparoscopic RYGB were retrospectively reviewed. Data regarding demographics,
      comorbidities, body mass index (BMI), Helicobacter pylori infection,
      gastrojejunal (GJ) anastomotic leaks, postoperative bleeding, operative time,
      type of suture material, and marginal ulcer formation were collected. Fisher's
      exact test was used for statistical analysis of discrete variables, and Student's
      t-test was used for continuous variables. Statistical significance was set at an
      alpha of 0.05. RESULTS: The overall marginal ulceration rate was 7%. Demographic
      data (age, gender distribution, BMI) did not differ significantly between
      patients who experienced marginal ulceration and those who did not (p > 0.05).
      Similarly, technical factors (choice of permanent or absorbable suture for the GJ
      anastomosis, attending as primary surgeon, robotic GJ, operative time,
      postoperative hematocrit drop) were not statistically different between the two
      groups (p > 0.05). Finally, the prevalence of comorbidities (diabetes,
      hypertension, obstructive sleep apnea, musculoskeletal complaints, dyslipidemia,
      gastroesophageal reflux disease [GERD] and peptic ulcer disease [PUD]) did not
      differ significantly between the two groups (p > 0.05). However, preoperative H.
      pylori infection, although adequately treated, was twice as common among the
      patients who had marginal ulceration (32%) as among those who did not (12%) (p =
      0.02). All the patients who experienced marginal ulcers had complete resolution
      of symptoms with proton pump inhibitors and sucralfate. No reoperations were
      required for marginal ulceration. CONCLUSION: Helicobacter pylori may potentiate
      marginal ulcer formation. The authors hypothesize that H. pylori damages the
      mucosal barrier in a way that persists postoperatively, which may precipitate
      marginal ulceration even when the organism has been medically eradicated.

PMID- 17514404
TI  - Diversity of the bacterial communities associated with the azooxanthellate deep
      water octocorals Leptogorgia minimata, Iciligorgia schrammi, and Swiftia exertia.
AB  - This study examined the microbiota associated with the marine azooxanthellate
      octocorals Leptogorgia minimata, Swiftia exertia, and Iciligorgia schrammi
      collected from moderate depths (45 m). Traditional aerobic plate culture,
      fluorescence in situ hybridization (FISH), and molecular identification of the
      16S rDNA region were used for this purpose. In general, cultures were found to be
      selective for Gammaproteobacteria, Alphaproteobacteria, and Firmicutes.
      Interestingly, FISH counts for Firmicutes in the whole coral (holobiont) were
      near the detection limit of this assay, representing less than 6% of the total
      detectable microbiota in all counts. Proteobacteria, especially Alpha- and
      Gammaproteobacteria, made up the majority of the total microbiota in the
      holobionts. In addition, the absence of zooxanthellae in these three corals was
      confirmed by the use of polymerase chain reaction (PCR) and dinoflagellate
      specific primers, and spectrophotometric chlorophyll pigment measurements. No
      evidence of zooxanthellae could be found in any of the corals by either of these
      techniques. This is the first study examining the microbiota marine octocorals,
      which grow at moderate depth (40 to 100 m) in the absence of direct sunlight.

PMID- 17514405
TI  - Superiority of sonographic hematoma guided resection of mammogram only visible
      breast cancer: wire localization should be an exception--not the rule.
AB  - BACKGROUND: The goal of breast conservation in cancer treatment is to obtain
      adequate margins with minimum tissue loss to achieve acceptable oncologic and
      cosmetic outcome. The standard for resection of breast cancers visible only on
      mammogram is wire localization (WL), which has a high rate of positive margins.
      We hypothesized that sonographic hematoma guided (SHG) resection achieves better
      margin clearance while minimizing volume of resection by more accurate lesion
      localization. METHODS: This retrospective study was conducted at the University
      Comprehensive Breast Center. Consecutive patients over the span of one year,
      undergoing breast conservation for stereotactic biopsy proven cancers that were
      not visualized on ultrasound were studied. SHG and WL technique were compared for
      age, mammographic abnormality, and tumor characteristics. Outcome variables
      included closest margin of resection, volume of resection, resection index
      (resection volume/tumor volume), and rate of margin revision. RESULTS: Forty-five
      patients had SHG, while 51 had WL lumpectomy. The SHG and WL groups were similar
      in age, mammographic abnormality, tumor type, and stage. Median (25th-75th
      centile) tumor size was larger in SHG group vs WL group [1.2 (1.1-1.3) vs 0.8
      (0.4-1.4) cm; P = .009]. Median (25th-75th centile) closest margin in SHG vs WL
      group was 5.0 (5.0-8.0) vs 4.0 (1.0-10) mm [P = .0041]. Median (25th-75th
      centile) resection volume in SHG vs WL group was 85.0 (60.0-128.0) vs 142.2 (54.4
      229.0) cm(3) [P = .0127]. Median (25th-75th centile) resection index in SHG vs WL
      group was 77.3 (59.3-285.7) vs 337.1 (88.9-3982.2) [P = .0004]. Margin was
      revised in 2 (4.4%) SHG vs 8 (15.7%) WL patients [P = .0978]. CONCLUSION:
      Sonographic hematoma guided lumpectomy is superior to wire localization in
      obtaining adequate margins with minimal volume of resection.

PMID- 17514406
TI  - Validation of a breast cancer nomogram for predicting nonsentinel lymph node
      metastases after a positive sentinel node biopsy.

PMID- 17514407
TI  - Sentinel lymph node biopsy performed after neoadjuvant chemotherapy is accurate
      in patients with documented node-positive breast cancer at presentation.
AB  - BACKGROUND: The optimal strategy for incorporating lymphatic mapping and sentinel
      lymph node biopsy into the management of breast cancer patients receiving
      neoadjuvant chemotherapy remains controversial. Previous studies of sentinel node
      biopsy performed following neoadjuvant chemotherapy have largely reported on
      patients whose prechemotherapy, pathologic axillary nodal status was unknown. We
      report findings using a novel comprehensive approach to axillary management of
      node-positive-patients receiving neoadjuvant chemotherapy. METHODS: We evaluated
      54 consecutive breast cancer patients with biopsy-proven axillary nodal
      metastases at the time of diagnosis that underwent lymphatic mapping with nodal
      biopsy as well as concomitant axillary lymph node dissection after receiving
      neoadjuvant chemotherapy. All cases were treated at a single comprehensive cancer
      center between 2001 and 2005. RESULTS: The sentinel node identification rate
      after delivery of neoadjuvant chemotherapy was 98%. Thirty-six patients (66%) had
      residual axillary metastases (including eight patients that had undergone
      resection of metastatic sentinel nodes at the time of diagnosis), and in 12 cases
      (31%) the residual metastatic disease was limited to the sentinel lymph node. The
      final, post-neoadjuvant chemotherapy sentinel node was falsely negative in three
      cases (8.6%). The negative final sentinel node accurately identified patients
      with no residual axillary disease in 17 cases (32%). CONCLUSIONS: Sentinel lymph
      node biopsy performed after the delivery of neoadjuvant chemotherapy in patients
      with documented nodal disease at presentation accurately identified cases that
      may have been downstaged to node-negative status and can spare this subset of
      patients (32%) from experiencing the morbidity of an axillary dissection.

PMID- 17514408
TI  - Lymphatic mapping and sentinel lymph node biopsy for locally recurrent breast
      cancer: new clues to understanding the biology of chest wall relapse.

PMID- 17514409
TI  - Impact of splenectomy in patients with gastric adenocarcinoma of the cardia.
AB  - Previous reports have suggested that splenectomy treatment of gastric carcinoma
      of the cardia results in poor patient outcome, but the reason for this is
      unclear. This study aimed to clarify the impact of splenectomy for gastric
      carcinoma patients. A total of 118 patients with gastric carcinoma of the cardia
      were enrolled in this study. The characteristics of patients with lymph node
      metastasis at the splenic hilum were determined, and the effects of lymph node
      dissection or splenectomy on postoperative morbidity, mortality, and pattern of
      recurrence were evaluated. Advanced tumors were common in patients with lymph
      node metastasis at the splenic hilum, Siewert type III, greater curvature sites,
      larger and deeper tumors, multiple metastatic lymph nodes, and high incidences of
      para-aortic lymph node metastasis frequently observed. The effectiveness of lymph
      node dissection of the splenic hilum was low and equal to that of dissection of
      the para-aortic lymph nodes. Postoperative morbidity, as represented by
      pancreatic fistula, was high following splenectomy or pancreaticosplenectomy, but
      patient mortality did not occur. Hematogenous metastasis was common, as well as
      peritoneal metastasis after curative gastrectomy. Splenectomy should be limited
      in those patients with gastric cardia tumors invading the spleen or with
      metastatic bulky lymph nodes extending to the spleen.

PMID- 17514410
TI  - Modified jejunoileal bypass surgery with biliary diversion for morbid obesity and
      changes in liver histology during follow-up.
AB  - BACKGROUND AND AIMS: Bariatric surgery is the most effective treatment for morbid
      obesity. The classic procedure, jejunoileal bypass, has many complications
      including rapid progress of liver disease. The senior author (I.F.) has developed
      a modification of jejunoileal bypass, which we believe overcomes many of the
      shortcomings of the classic procedure. METHODS: Consecutive patients referring
      for bariatric surgery were included. A modified jejunoileal bypass in which the
      defunctionalized limb is eliminated by anastomosing its ends to the gall bladder
      and cecum was performed. Liver biopsies were taken during operation and at a mean
      of 16 months later. The patients were followed for 5 years. RESULTS: Forty-three
      patients were enrolled. The mean value of weight and body mass index (BMI) fell
      from 128 kg and 46 kg/m(2) before operation to 85 kg and 31 kg/m(2) at 5 years,
      respectively (p < 0.001). There was no significant change in the degree of liver
      steatosis and necroinflammation. The mean liver fibrosis score increased from 0.1
      to 0.9 (p = 0.015). No sign of advanced liver disease was observed during the 5
      year follow-up. CONCLUSION: The modified jejunoileal bypass is very effective in
      inducing and maintaining weight loss for 5 years and does not lead to hepatic
      failure or rapid progression of liver disease.

PMID- 17514411
TI  - Do European corn borer females detect and avoid laying eggs in the presence of 20
      hydroxyecdysone?
AB  - European corn borer larvae detect and avoid feeding in the presence of
      phytoecdysteroids (PEs) such as 20-hydroxyecdysone (20E). Therefore, we
      hypothesized that females would have taste receptors similar to larvae and avoid
      laying eggs in the presence of 20E. We found female-specific taste sensilla on
      the tarsi that respond to 20E at concentrations as low as 10(-6) M, a threshold
      comparable to that of larvae. However, in choice tests, females laid a similar
      number of eggs on 20E-treated and on nontreated artificial substrates (filter
      paper, glass, and nylon), although they spent significantly more time in
      behavioral sequences related to substrate assessment when 20E was present. In
      contrast, when given a choice between maize plants (eight leaves) sprayed with
      20E or only the solvent, females laid 70% fewer eggs on the treated than on
      control plants. These observations suggest that other chemical cues of plant
      origin must be present at the same time as 20E for females to modify their
      oviposition behavior.

PMID- 17514412
TI  - Modification of axial fiber contact residues impact sickle hemoglobin
      polymerization by perturbing a network of coupled interactions.
AB  - The identity of intermolecular contact residues in sickle hemoglobin (HbS) fiber
      is largely known. However, our knowledge about combinatorial effects of two or
      more contact sites or the mechanistic basis of such effects is rather limited.
      Lys16, His20, and Glu23 of the alpha-chain occur in intra-double strand axial
      contacts in the sickle hemoglobin (HbS) fiber. Here we have constructed two novel
      double mutants, HbS (K16Q/E23Q) and (H20Q/E23Q), with a view to delineate
      cumulative impact of interactions emanating from the above contact sites. Far-UV
      and visible region CD spectra of the double mutants were similar to the native
      HbS indicating the presence of native-like secondary and tertiary structure in
      the mutants. The quaternary structures in both the mutants were also preserved as
      judged by the derivative UV spectra of liganded (oxy) and unliganded (deoxy)
      forms of the double mutants. However, the double mutants displayed interesting
      polymerization behavior. The polymerization behaviour of the double mutants was
      found to be non-additive of the individual single mutants. While HbS (H20Q/E23Q)
      showed inhibitory effect similar to that of HbS (E23Q), the intrinsic inhibitory
      propensity of the associated single mutants was totally quelled in HbS
      (K16Q/E23Q) double mutant. Molecular dynamics (MD) simulations studies of the
      isolated alpha-chains as well as a module of the fiber containing the double and
      associated single mutants suggested that these contact sites at the axial
      interface of the fiber impact HbS polymerization through a coupled interaction
      network. The overall results demonstrate a subtle role of dynamics and
      electrostatics in the polymer formation and provide insights about interaction
      linkage in HbS fiber assembly.

PMID- 17514413
TI  - Purification and characterization of a novel beta-D-galactosides-specific lectin
      from Clitoria ternatea.
AB  - A lectin present in seeds of Clitoria ternatea agglutinated trypsin-treated human
      B erythrocytes. The sugar specificity assay indicated that lectin belongs to
      Gal/Gal NAc-specific group. Hence the lectin, designated C. ternatea agglutinin
      (CTA), was purified by the combination of acetic acid precipitation, salt
      fractionation and affinity chromatography. HPLC gel filtration, SDS
      polyacrylamide gel electrophoresis and mass spectrometry indicated that the
      native lectin is composed of two identical subunits of molecular weight 34.7 kDa
      associated by non covalent bonds. The N-terminal sequence of CTA shared homology
      with Glycine max and Pisum sativum. Complete sequence was also found to be
      homologous to S-64 protein of Glycine max, suggesting that CTA probably exhibits
      both hemagglutination and probably sugar uptake activity. The carbohydrate
      binding specificity of the lectin was investigated by quantitative turbidity
      measurements, and percent inhibition assays. Based on these assays, we conclude
      that CTA binds beta-D: -galactosides, and also may has an extended specificity
      towards non-reducing terminal Neu5Acalpha2,6Gal.

PMID- 17514414
TI  - Effect of heat and pH denaturation on the structure and conformation of
      recombinant human hepatic stimulator substance.
AB  - Hepatic stimulator substance (HSS) is a novel liver-specific growth-promoting
      factor. Although HSS has been successfully crystallized, several properties of
      this protein have yet to be determined. This study shows that recombinant human
      HSS (rhHSS) is a dimer with a molecular mass of 31 kDa, the protein is weakly
      acidic and has an isoelectric point (pI) of 4.50. RhHSS was able to protect
      hepatoma cells from H2O2-induced apoptosis and to stimulate cell growth. The
      recombinant protein was thermostable up to 80 degrees C and resistant to changes
      in pH, as determined by synchronous fluorescence and far-UV circular dichroism
      (CD). Within the range of pH 4.0-10.0, rhHSS assumed a folded conformation
      identical to the secondary structure of the original, native protein and a native
      like far-UV CD spectrum. Denatured rhHSS could be partly reconstituted with
      respect to its structure, but not its activity. Thus, rhHSS is a structurally
      stable protein insensitive to thermal and acid-alkaline denaturation.

PMID- 17514415
TI  - Supplementation with vitamins E plus C or soy isoflavones in ovariectomized rats:
      effect on the activities of Na(+), K (+)-ATPase and cholinesterases.
AB  - Since a previous study demonstrated that ovariectomized rats present an
      activation of Na(+), K(+)-ATPase and acetylcholinesterase (AChE) activities, in
      the present study we investigated the influence of vitamins E plus C or soy
      isoflavones on the effects elicited by ovariectomy on the activities of these
      enzyme in hippocampus of ovariectomized rats. We also determined the effect of
      the same compounds on the reduction of serum butyrylcholinesterase (BuChE)
      activity caused by ovariectomy. Female adult Wistar rats were assigned to one of
      the following groups: sham (submitted to surgery without removal of the ovaries)
      and ovariectomized. Seven days after surgery, animals were treated for 30 days
      with a single daily intraperitoneous injection of vitamins E (40 mg/kg) plus C
      (100 mg/kg) or saline (control). In another set of experiments, the rats were fed
      for 30 days on a special diet with soy protein or a standard diet with casein
      (control). Rats were sacrificed after treatments and the hippocampus was
      dissected and serum was separated. Data demonstrate that vitamins E plus C
      reversed the activation of Na(+), K(+)-ATPase and AChE in hippocampus of
      ovariectomized rats. Conversely, soy protein supplementation reversed the
      increase of AChE activity, but not of Na(+), K(+)-ATPase activity, caused by
      ovariectomized group. Neither treatment was able to reverse the reduction of
      serum BuChE activity. Furthermore, treatments with vitamins E plus C or soy were
      unable to reverse the decrease in estradiol levels caused by ovariectomy. Our
      findings show that the treatment with vitamins E plus C significantly reversed
      the effect of ovariectomy on hippocampal Na(+), K(+)-ATPase and AChE activities.
      However, a soy diet that was rich in isoflavones was able to reverse just the
      increase of AChE. Neither treatment altered the reduction in serum BuChE
      activity. Taken together, these vitamins and soy may have a protective role
      against the possible brain dysfunction observed in some menopause women. Vitamins
      E plus C and soy isoflavones may be a good alternative as a novel therapeutic
      strategy.

PMID- 17514419
TI  - Differences in doublecortin immunoreactivity and protein levels in the
      hippocampal dentate gyrus between adult and aged dogs.
AB  - Doublecortin (DCX), a microtubule-associated protein, specifically expresses in
      neuronal precursors. This protein has been used as a marker for neuronal
      precursors and neurogenesis. In the present study, we observed differences in DCX
      immunoreactivity and its protein levels in the hippocampal dentate gyrus between
      adult and aged dogs. In the adult dog, DCX immunoreactive cells with well-stained
      processes were detected in the subgranular zone of the dentate gyrus. Numbers of
      DCX immunoreactive cells in the dentate gyrus of the aged dog were significantly
      decreased compared to those in the adult dog. DCX immunoreactive cells in both
      adult and aged dog did not show NeuN (a marker for mature neurons)
      immunoreactivity. NeuN immunoreactivity in the aged dog was poor compared to that
      in the adult dog. DCX protein level in the aged dentate gyrus was decreased by
      80% compared to that in the adult dog. These results suggest that the reduction
      of DCX in the aged hippocampal dentate gyrus may be involved in some neural
      deficits related to the hippocampus.

PMID- 17514418
TI  - Socioeconomic status and health behaviors in adolescence: a review of the
      literature.
AB  - OBJECTIVE: The goal of this review was to determine the direction of associations
      between SES and health behaviors during the period of adolescence. METHOD: We
      searched the PsychInfo and Pubmed databases for studies that measured the
      association between SES and cigarette smoking, alcohol consumption, marijuana
      use, diet, and physical activity in adolescents between 10- and 21-years old.
      RESULTS: Associations between SES and health behaviors conformed to two patterns.
      First, low SES was associated with poorer diets, less physical activity, and
      greater cigarette smoking. Second, there was no clear pattern of associations
      between SES and alcohol consumption or marijuana use. CONCLUSION: Results from
      this review indicate that, although some associations between SES and health
      behaviors exist during adolescence, the associations are not as robust as those
      in adulthood. Efforts to curb poor diet, inactivity, and smoking behaviors should
      target low SES adolescents, whereas efforts to curb teen drinking and marijuana
      use may be useful across the SES spectrum.

PMID- 17514420
TI  - Oxidative stress and S100B protein in cirrhotic children.
AB  - Cirrhosis represents the terminal stage of a number of chronic liver diseases.
      Consequences include accumulation of toxic metabolic wastes, reduced synthesis of
      key proteins, increased portal venous pressure, and portosystemic shunting. We
      conducted a case-control study to assess the serum levels of S100B protein and
      parameters of oxidative stress, superoxide dismutase (SOD), catalase (CAT) and
      oxidative stress measured by the thiobarbituric acid method (TBARS), in a group
      of 14 pediatric patients with cirrhosis. No differences were found between groups
      in S100B protein levels. SOD activity and TBARS levels were higher; and CAT
      activity was lower in the cirrhotic group. A negative correlation between S100B
      and TBARS in the case group was found (r = -0.815, p = 0.001). CONCLUSIONS: This
      study didn't indicate a possible role of S100B serum levels as marker of brain
      damage in cirrhotic children but suggest a possible relation between astrocyte
      function and oxidative damage in cirrhotic children.

PMID- 17514422
TI  - Amyloid-beta-peptide reduces the expression level of mitochondrial cytochrome
      oxidase subunits.
AB  - Mitochondrial dysfunction is an important cause of neurological disorder
      including Alzheimer's disease (AD). Mitochondria play a key role in the
      generation of reactive oxygen species (ROS), resulting in oxidative damage to
      neuronal cell and cellular compartments in the AD brain. Cytotoxicity induced by
      amyloid-beta (Abeta), a protein fragment of 25-35 amino acids in amyloid plaques
      has been shown to have neuro-toxic properties. They seem to involve mitochondrial
      dysfunction, but the underlying mechanisms are not clearly understood. The
      purpose of this study was to assess whether Abeta induced mitochondrial
      dysfunction involves changes in cytochrome c oxidase (COX) expression. We
      measured the activities of COX after expose of SK-N-SH cells (a human
      neuroblastoma cell line) to Abeta. We found that levels of mRNAs expressing
      mitochondrial COX subunits decreased significantly in Abeta-treated SK-N-SH cells
      in a dose-dependent manner. Human mitochondrial transcription factor-1 (TFAM)
      mRNA level also decreased after Abeta-treatment. These results suggest that Abeta
      modulates the mitochondrial gene expression through a decrease in TFAM.

PMID- 17514421
TI  - Synergetic effects of caspase 3 and mu-calpain in XIAP-breakdown upon focal
      cerebral ischemia.
AB  - Dysregulation of apoptosis is involved in a wide spectrum of disease ranging from
      proliferative to neurodegenerative disorders. The recently discovered X-linked
      inhibitor of apoptosis protein (XIAP) is among the most potent inhibitors of
      apoptosis. This protein binds to and inhibits both initiator caspases and
      effector caspases such as caspase-3. The aim of this study was to investigate the
      relationships between XIAP-breakdown, caspase activation in the development of
      delayed infarct upon ischemia. We demonstrated that endogenous XIAP is cleaved at
      least into two fragments during reperfusion following the ischemic insult. The
      two fragments produced seem to be related to caspase-3 and mu-calpain activities,
      which are massively enhanced in tissues challenged by ischemia. Therefore,
      degradation of XIAP by mu-calpain in our system may decrease the activation
      threshold of caspase-3 normally held in check by the IAPs and/or lead to auto
      activation of other caspases.

PMID- 17514423
TI  - Left ventricular volume measurement by the conductance catheter and variations in
      the hematocrit in small animals.
AB  - Cardiac performance is quantitatively and continuously assessed from pressure
      volume signals by using the conductance catheter technique even in small animals.
      Conductivity of blood, however, is dependent on hematocrit (Hct). Interdependence
      between hematocrit and volume measurement by the conductance catheter has been
      evaluated. In 12 male Wistar rats weighing 400-475 g, anesthetized and
      artificially ventilated, Hct was gradually lowered by isovolumic hemodilution
      ranging from 50% to 7%. Heparinized blood samples were drawn at decreasing Hct
      levels for centrifugation, for automated Hct measurement by a blood gas analyzer,
      and for conductance catheter volume measurements (CCV) in calibrated cuvettes.
      Substitution of about 2 ml colloid solution lowered the Hct initially from 47 +/-
      2% to 36 +/- 3%; at the same time, CCV output rose by 36 +/- 14% for definite
      blood volume. There is a strong inverse linear relationship (absolute value of r
      > 0.96; P < 0.0001) between relative volume units (RVU) displayed by the volume
      acquisition device and the hematocrit for any calibrated blood cuvette. Slopes of
      the regression lines increase proportionally to the calibration volumes (28.3
      microl: -0.25; 63.6 microl: -0.57; 113.1 microl: -0.92). These data document the
      direct interdependence between Hct and CCV. Consequently, careful Hct correction
      of the RVU recordings is necessary especially in small animals where even small
      amounts of substituted solutions result in a marked decrease in Hct and, thus, in
      pronounced blood volume misreadings.

PMID- 17514424
TI  - Oral proton pump inhibitors are as effective as endoscopic treatment for bleeding
      peptic ulcer: a prospective, randomized, controlled trial.
AB  - In managing patients with bleeding peptic ulcers, it has been reported that
      pharmacologic treatment can be an alternative to endoscopic treatment. We
      compared the hemostasis rates of the endoscopic treatment, hemoclipping, and the
      pharmacologic treatment, oral proton pump inhibitors (PPIs), in bleeding peptic
      ulcer. A randomized prospective study was performed on 129 bleeding peptic ulcer
      patients with hematemesis or melena. Sixty-two patients were treated by
      endoscopic hemoclipping and subsequently H(2) receptor antagonists were injected
      intravenously (hemoclipping group), and 67 patients were treated with an oral PPI
      without endoscopic treatment (PPI group). The 24-hr gastric pH test was performed
      sequentially following the treatment. The initial hemostasis rate of the
      hemoclipping group was 93.5% (58/62) and the rebleeding rate was 6.9% (4/58), and
      the hemostasis rate of the PPI group was 92.5% (62/67) and the rebleeding rate
      was 7.5% (5/67), which were not different. The 24-hr gastric pH was 4.54+/-2.56
      in the hemoclipping group and 5.97+/-1.30 in the PPI group (P<0.037). In the
      bleeding peptic ulcer patients, the hemostasis rate with the oral administration
      of PPIs was not different from that with the endoscopic hemoclipping treatment.

PMID- 17514425
TI  - Deaths of Mexican and Central American children along the US border: the Pima
      County Arizona experience.
AB  - Using data obtained through the Arizona Child Fatality Review Program, we
      reviewed deaths of all children (birth-17 years) who were Mexican or Central
      American residents and who died in Pima County, Arizona during the years 1995
      2004. They accounted for 5% of all pediatric deaths in the county. Causes of
      death were motor vehicle collision (32%), environmental exposure (17%),
      prematurity (11%), other trauma (11%) and other medical conditions (28%). Fifty
      three percent of these children were in the US seeking medical care; 36% were
      undocumented migrants. Significant trends over the 10 years were toward fewer
      children seeking medical care and more children dying while border crossing.
      Border health and economic disparities affected overall child mortality in this
      US county, but current prevention efforts are unlikely to affect this population
      group.

PMID- 17514426
TI  - Demography of exercise among Californians of Korean descent: a cross-sectional
      telephone survey.
AB  - This study describes aerobic exercise and walking for exercise behaviors among
      the Korean American population, a rapidly growing minority. Data for this study
      were drawn from a representative survey of Californians of Korean descent (N =
      2,830) conducted by telephone; 86% of eligible participants completed interviews
      in either Korean or English. Sample characteristics closely approximated those
      for Koreans in the 2000 United States Census for California. The data show that
      32.8% of Koreans vigorously exercise or walk for exercise, but walking regimens
      and more vigorous modes of exercise are employed by different subgroups. Women,
      less acculturated, married persons, and less well educated are particularly low
      in vigorous exercise. Korean Americans walk for exercise much less than majority
      groups, although they engage in vigorous physical activity on a roughly
      equivalent basis. Interventions to promote physical activity should be adapted
      not only for the Korean culture but also for specific subgroups defined
      demographically.

PMID- 17514427
TI  - Bacterial diversity of East Calcutta Wet land area: possible identification of
      potential bacterial population for different biotechnological uses.
AB  - The extent of microbial diversity in nature is still largely unknown, suggesting
      that there might be many more useful products yet to be identified from soil
      microorganisms. This insight provides the scientific foundation for a renewed
      interest in examining soil microorganisms for novel commercially important
      products. This has led us to access the metabolic potential of soil
      microorganisms via cultivation strategy. Keeping this in mind, we have performed
      a culture-dependent survey of important soil bacterial community diversity in
      East Calcutta Wetland area (Dhapa Landfill Area). We describe isolation of 38
      strains, their phenotypic and biochemical characterization, and finally molecular
      identification by direct sequencing of polymerase chain reaction (PCR)-amplified
      16S rRNA gene products. We have isolated and identified strains able to fix
      nitrogen, produce extracellular enzymes like protease, cellulase, xylanase, and
      amylase, and solubilize inorganic phosphates. Some isolates can synthesize
      extracellular insecticidal toxins. We find a good correlation between biochemical
      and phenotypic behavior and the molecular study using 16S rRNA gene of the
      isolates. Furthermore, our findings clearly indicate the composition of
      cultivable soil bacteria in East Calcutta Wetland Area.

PMID- 17514429
TI  - Incidence and predictors of severe bleeding during warfarin treatment.
AB  - BACKGROUND: Optimal warfarin prescription requires correct, individualized
      assessment of the warfarin-related bleeding risk, which randomised controlled
      trials may underestimate . Observational studies have reported a range of
      bleeding risks that differ 40-fold. This variation may be caused by time trends,
      variation in bleeding definition and study subject selection. We investigated the
      incidence of, and risk factors for severe bleeding in un-selected warfarin
      treated patients from Sweden. METHODS: Between 2001 and 2005, 40 centres
      recruited warfarin-naive patients commencing warfarin therapy and followed them
      prospectively with continuous registration of clinical data. The primary outcome
      was severe bleeding, according to the WHO universal definition of severe adverse
      drug reactions. The influence of potential risk factors was investigated by means
      of a Cox proportional-hazards model. RESULT: A total of 1523 patients contributed
      1276 warfarin-exposed patient-years. The incidence of first-time severe bleeding
      was 2.3 per 100 patient-years (95% confidence interval 1.4 to 3.1). Male sex and
      use of drugs potentially interacting with warfarin were the only independent risk
      factors of severe bleeding, with hazard ratios of 2.8 and 2.3, respectively. Age,
      target International Normalized Ratio (INR), time spent outside target INR range,
      and warfarin dose requirement were not significantly associated with bleeding
      risk. CONCLUSIONS: The risk of severe bleeding in a large naturalistic,
      prospective cohort of first-time warfarin users was lower than reported in some
      previous reports. Male gender was an independent predictor of severe bleeding as
      was the receipt of warfarin-interacting medications at the onset of
      anticoagulation therapy. Further studies are required to evaluate the effect
      these findings may have on the quality of current risk-benefit analysis involved
      in warfarin prescription.

PMID- 17514430
TI  - Microbubble potentiated transcranial duplex ultrasound enhances IV thrombolysis
      in acute stroke.
AB  - BACKGROUND: We studied whether 2 MHz transcranial color-coded duplex ultrasound
      (TCCD), combined with a second generation ECA, accelerate IV rtPA-thrombolysis in
      the acute phase of MCA stroke more than TCCD monitoring alone. METHODS: Non
      randomized acute MCA stroke patients undergoing IV rtPA-thrombolysis and 2 MHZ
      TCCD monitoring over 60 min, with (N = 11) or without (N = 15) additional
      continuous ECA (5 ml, SonoVue perfusion, were compared. Recanalization of the MCA
      was measured pre- and post-thrombolysis with the thrombolysis in brain ischemia
      (TIBI) grading system, clinical outcome was assessed at admission and 24 h after
      treatment using the NIH stroke scale (NIHSS). RESULTS: Patients who received ECA
      improved their NIHSS significantly more than those who were only TCCD monitored
      (Mann-Whitney U = 48.0; P = 0.050), and their flow signal improved more (Mann
      Whitney U = 40.0; P < 0.03). CONCLUSIONS: The results of this pilot study show
      that in IV-thrombolysis the use of ECA in addition to TCCD monitoring lead to a
      greater immediate clinical improvement and to a better flow signal.

PMID- 17514428
TI  - Which perspectives can endophenotypes and biological markers offer in the early
      recognition of schizophrenia?
AB  - The early recognition of schizophrenia seems crucial; various studies relate a
      longer duration-of-untreated-psychosis to a worse prognosis. We give an overview
      over common psychopathological early recognition instruments (BSABS, CAARMS,
      SIPS, IRAOS, ERIraos). However, many clinical symptoms of prodromal schizophrenia
      stages are not sufficiently specific. Thus we review recent contributions of
      neuroimaging and electrophysiological as well as genetic studies: which new
      diagnostic perspectives offer endophenotypes (such as P300, P50 sensory gating,
      MMN, smooth pursuit eye movements; indicating a specific genetic vulnerability)
      together with a better understanding of schizophrenic pathophysiology (state
      dependent biological markers, e.g. aggravated motor neurological soft signs
      during psychosis) in prodromal schizophrenia when still ambiguous clinical
      symptoms are present. Several examples (e.g. from COMT polymorphisms to working
      memory deficits) illustrate more specific underlying neuronal mechanisms behind
      behavioural symptoms. This way, a characteristic pattern of disturbed cerebral
      maturation might be distinguished in order to complement clinical instruments of
      early schizophrenia detection.

PMID- 17514431
TI  - Increased calcium bioavailability in mice fed genetically engineered plants
      lacking calcium oxalate.
AB  - Bioavailable calcium affects bone formation and calcification. Here we
      investigate how a single gene mutation altering calcium partitioning in the model
      forage crop Medicago truncatula affects calcium bioavailability. Previously, the
      cod5 M. truncatula mutant was identified which contains identical calcium
      concentrations to wild-type, but contains no oxalate crystals. In this study,
      equal number of male and female mice were randomly grouped and then fed one of
      four 45Ca-containing diets: M. truncatula extrinsically or intrinsically labeled,
      and cod5 extrinsically or intrinsically labeled. Absorption of the tracer was
      determined in the legs one day after consumption. The absorption was similar in
      the M. truncatula and cod5 extrinsically labeled diets; however, in the
      intrinsically labeled diets, calcium absorption was 22.87% (P < 0.001) higher in
      mice fed cod5. Our study presents the first genetic evidence demonstrating the
      nutritional impact of removing oxalate crystals from foods.

PMID- 17514432
TI  - A novel starch for the treatment of glycogen storage diseases.
AB  - OBJECTIVE: To determine whether a new starch offers better short-term metabolic
      control than uncooked cornstarch in patients with glycogen storage diseases
      (GSDs). STUDY DESIGN: A short-term double-blind cross-over pilot study comparing
      uncooked physically modified cornstarch (WMHM20) with uncooked cornstarch in
      patients with GSD types Ia, Ib and III. Twenty-one patients (ages 3-47, 9 female)
      were given 2 g/kg cornstarch or WMHM20 mixed in water. Blood glucose, lactate and
      insulin, and breath hydrogen and (13)CO2 enrichment were measured, at baseline
      and after each load. The hourly biochemical evaluations terminated when blood
      glucose was < or = 3.0 mmol/L, when the study period had lasted 10 h or when the
      patient wished to end the test. The alternative starch was administered under
      similar trial conditions a median of 10 days later. RESULTS: The median starch
      load duration was 9 h for WMHM20 versus 7 h for cornstarch. Glucose decreased
      more slowly (p = 0.05) and lactate was suppressed faster (p = 0.17) for WMHM20
      compared with cornstarch. Peak hydrogen excretion was increased (p = 0.05) when
      cornstarch was taken. CONCLUSION: These data indicate longer duration of
      euglycaemia and better short-term metabolic control in the majority of GSD
      patients with WMHM20 compared to cornstarch.

PMID- 17514433
TI  - Queuine mediated inhibition in phosphorylation of tyrosine phosphoproteins in
      cancer.
AB  - Protein phosphorylation or dephosphorylation is the most important regulatory
      switch of signal transduction contributing to control of cell proliferation. The
      reversibility of phosphorylation and dephosphorylation is due to the activities
      of kinases and phosphatase, which determine protein phosphorylation level of cell
      under different physiological and pathological conditions. Receptor tyrosine
      kinase (RTK) mediated cellular signaling is precisely coordinated and tightly
      controlled in normal cells which ensures regulated mitosis. Deregulation of RTK
      signaling resulting in aberrant activation in RTKs leads to malignant
      transformation. Queuine is one of the modified base of tRNA which participates in
      down regulation of tyrosine kinase activity. The guanine analogue queuine is a
      nutrient factor to eukaryotes and occurs as free base or modified nucleoside
      queuosine into the first anticodon position of specific tRNAs. The tRNAs are
      often queuine deficient in cancer and fast proliferating tissues. The present
      study is aimed to investigate queuine mediated inhibition in phosphorylation of
      tyrosine phosphorylated proteins in lymphoma bearing mouse. The result shows high
      level of cytosolic and membrane associated tyrosine phosphoprotein in DLAT
      cancerous mouse liver compared to normal. Queuine treatments down regulate the
      level of tyrosine phosphoproteins, which suggests that queuine is involved in
      regulation of mitotic signaling pathways.

PMID- 17514434
TI  - Isolation and characterization of a male sterility gene homolog BcMS2 from
      Chinese cabbage-pak-choi that expressing in an anther-specific manner.
AB  - A male sterility gene homolog, designated BcMS2, was isolated from flower buds
      using gene-specific primer pairs and was submitted to GenBank under accession
      number EF093533. Comparison of BcMS2 gene with MS2 from Arabidopsis thaliana and
      MS2Bnap from Brassica napus revealed some differences in gene structure and
      evolution. The full genomic DNA sequence of BcMS2 was 2,576 bp in length
      containing 8 exons and 7 introns, more than those of MS2Bnap but less than MS2.
      RT-PCR showed that BcMS2 gene expressed only in stage III flower buds of male
      fertile Chinese cabbage-pak-choi 'ZUBajh97-01B' and there were no detection in
      all organs of Polima cytoplasmic male sterility (CMS) line 'Bpol97-05A' and Ogura
      CMS line 'Bogu97-06A'. Furthermore, RT-PCR revealed that BcMS2 expressed only in
      anthers of male fertile material and there were no expression in sepals, petals,
      filaments and pistils. These results suggested that BcMS2 was an anther-specific
      gene and might be essential for the fertility of Chinese cabbage-pak-choi.

PMID- 17514435
TI  - [The German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS) 2003-2006 - a milestone in paediatrics].

PMID- 17514436
TI  - [The results of the German Health Interview and Examination Survey for Children
      and Adolescents (KiGGS) - a unique data collection concerning the health of the
      rising generation].

PMID- 17514437
TI  - [The German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS): an overview of its planning, implementation and results taking into
      account aspects of quality management].
AB  - The aim of the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS) was to improve the information available on the health of the
      up-and- coming generation in Germany and to fill gaps in knowledge. This was to
      be done using a nationwide representative investigation and survey of children
      and adolescents aged 0 to 17. From May 2003 to May 2006, 17,641 girls and boys
      took part in the study at 167 locations in Germany; along with their parents'
      input they provided a unique pool of information. From the point of view of
      quality management, there is a description of the planning, structures, efficient
      use of funding, implementation and planned evaluation of the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS). In this
      description, the quality achieved is evaluated by comparing what was actually
      achieved with the targets set. In this manner, a comprehensive overview can be
      provided of the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS): what it concerns, its modular structure, the co-operation
      partners involved, institutions financing it, regulatory processes accompanying
      it and strategies for evaluation. At the same time, it is shown how the
      individual publications in the journal for public health, health research and
      health protection (Bundesgesundheitsblatt) special issue no. 5/6 2007 connect to
      one another and to the issue as a whole.

PMID- 17514438
TI  - [The German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS): sample design, response and nonresponse analysis].
AB  - From May 2003 to May 2006, the Robert Koch Institute conducted the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS). Aim of
      this nationwide interview and examination survey was to collect, for the first
      time, comprehensive and nationwide data on the health status of children and
      adolescents aged 0 to 17 years. Subject recruitment was carried out in two steps:
      first, 167 study locations (sample points) were chosen; second, subjects were
      selected from the official registers of residents of the local residents'
      registration offices. The percentage of quality-neutral drop-outs was
      comparatively low (5.3%). The participation rate was 66.6% and showed only little
      variation between age groups and sexes, but marked variation between resident
      aliens and Germans, between inhabitants of cities with a population of 100,000 or
      more and sample points with fewer inhabitants, as well as between the old West
      German states and the newly-formed German states (incl. Berlin). A total of
      17,641 children and adolescents were surveyed, of whom 8,985 were boys and 8,656
      were girls. The completeness of the data sets in relation to the modules was
      good. The main reasons for non-participation were failure to appear at an agreed
      appointment time (or cancellation of the appointment at short notice), the
      refusal of the child/adolescent himself, or lack of interest of the parents.

PMID- 17514439
TI  - [The German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS): study management and conduct of fieldwork].
AB  - From May 2003 to May 2006, the Robert Koch Institute conducted the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS). Nationwide
      data collection in 167 cities and municipalities was carried out by 4 survey
      teams, each consisting of a physician, centre interviewer, examiner, medical
      laboratory technician, environmental interviewer. Regional and seasonal factors
      were excluded by systematised route planning. Invitation of the participants and
      appointments for examinations were handled by a survey office with subsidised
      service telephone. Data processing in the survey office was performed using an
      SQL data base system programmed in the RKI. One central and several regional
      members of staff performing preparatory field visits were responsible for finding
      suitable examination rooms and for subject recruitment respectively. To further
      increase the response rate, continuous public relation actions were established.
      The survey involved questionnaires filled in by parents and parallel
      questionnaires for children from the age of 11 years onwards, physical
      examinations and tests and a computer assisted personal interview performed by
      the physician. The wide range of blood and urine testing carried out at central
      laboratories required standardised transport logistics. To achieve a high degree
      of standardisation of the survey, the examination teams were initially trained
      and then underwent continuous further training. The concept of quality management
      covered action of internal and independent external quality control monitoring
      each data collecting and data processing step as well as the training courses.
      CONCLUSION: Dedicated public relations activities and the deployment of staff
      performing preparatory field visits increased the willingness of the subjects to
      participate. Intensive personnel care and continuous quality checks contribute to
      increased job satisfaction and data quality. By bindingly defining all laboratory
      diagnostic processes as well as transport logistics, high-quality laboratory test
      results are ensured. The conduct of the study from design via conduct to data
      processing and analysis by one institution guarantees complete control of all
      steps of the survey.

PMID- 17514440
TI  - [The German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS): data management].
AB  - In the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS), comprehensive, nationwide representative data on the state
      of health of children and adolescents were collected for the first time. During
      the 3-year data collection phase of the survey, 17,641 subjects were examined and
      interviewed and approx. 1,500 items were recorded. Data management was not
      limited to survey data collection, administration and quality assurance alone,
      but also comprised the provision of tools for the management and control of
      process data, as well as for managing survey-specific business processes. In the
      context of the KiGGS study, numerous components for supporting the extensive and
      complex processes were developed for the study staff. Here the primary focus was
      on subject and sample point administration, scheduling, sampling, reporting,
      field logistics and laboratory data management. Thanks to the computer-based
      processing of routine tasks involved in the organisation of the field work, ease
      of work and project progress control were enhanced significantly. To some extent,
      KiGGS-specific components have already been used in other studies and only minor
      adaptations were needed for the transfer. The main emphasis with regards to
      survey data management was on the standardisation of methods for data processing,
      data control and data cleaning. Here, a wealth of previous experiences was
      available as a starting point. The established quality assurance methods were
      standardised to a large extent and partly automated and complemented by data base
      tools for the management and documentation of survey instruments and quality
      assurance measures. All these measures combined made it possible to provide data
      users with a controlled and cleaned final data set, including a detailed
      documentation.

PMID- 17514441
TI  - [External quality assurance in the German Health Interview and Examination Survey
      for Children and Adolescents (KiGGS). Procedure and results].
AB  - The results of the German Health Interview and Examination Survey for Children
      and Adolescents (KiGGS) of the Robert Koch Institute (RKI) will be of great
      importance for health policy and research. Therefore, in this study internal
      quality assurance was supplemented by an external quality assurance which was
      carried out by the institute of epidemiology at the GSF National Research Center
      for Environment and Health. The subjects were the interviewer training, sampling
      and response, field work and data management. External quality assurance was
      defined as 'an audit of internal quality assurance measures and systematic
      observation and spot checks to ensure quality requirements were fulfilled'. The
      requirements followed the manual of operation and the recognized epidemiologic
      standards and guidelines. For the different subjects, tests and detailed check
      lists were developed and used. The quality requirements were fulfilled: The field
      work was performed with high quality and remarkable engagement over the whole
      time from May 2003 to May 2006, which resulted in high response and data quality.
      An extensive, efficient quality management system was in place for the data
      management.

PMID- 17514442
TI  - [Sociodemographic characteristics in the German Health Interview and Examination
      Survey for Children and Adolescents (KiGGS) - operationalisation and public
      health significance, taking as an example the assessment of general state of
      health].
AB  - The German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS) was conducted from May 2003 to May 2006 by the Robert Koch Institute in
      167 communities representative of Germany. By collecting comprehensive and
      nationally representative data on the health status of children and adolescents
      aged 0 to 17 years, the study aimed to fill a longstanding evidence gap. Data
      from 17,641 study participants will be analysed in a timely and systematic manner
      by the Robert Koch Institute. Initially mainly descriptive analyses as presented
      in the current special issue on the KiGGS study, provide information on the
      distribution of main health characteristics according to sociodemographic key
      variables, including age, sex, region of residence (former East/West Germany),
      social status, and migrant background. We report here the rationale for a
      standard set of stratifying variables and the operationalisation of composite
      variables. Furthermore, we illustrate the public health relevance of the observed
      group differences using the example of an important health indicator: parents'
      evaluation of their children's general state of health.

PMID- 17514443
TI  - [Children and adolescents in Germany with a migration background. Methodical
      aspects in the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS)].
AB  - A migration-specific approach was used in the German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS) and thus it was possible
      for the first time to include children with a migration background in a
      nationwide health survey in Germany in a number corresponding to their percentage
      of the population. This article presents the migration-specific approach used in
      KiGGS as well as a definition of the term "migrant" and its operationalisation.
      In addition, we analyse the representativity of the migrant subsample and present
      data on its composition. Altogether 2,590 children and adolescents with a
      migration background (both parents) took part in the study; in the weighted
      sample they account for 17.1% of all children and adolescents. Another 8.3% of
      the children and adolescents have one parent with a migration background. The two
      largest groups among the migrant children are Germans from Russia (29.9%) and
      children and adolescents of Turkish origin (28.2%). There are differences between
      migrants and non-migrants related to socio-economic status and place of living
      (rural/urban and East/West). Analyses of the representativity of the migrant
      sample show that children and adolescents with a lower level of education are
      under-represented, whereas there were no differences with regard to sex, the
      fathers' occupation or the mothers' smoking status. Non-respondents rate their
      children's health better than respondents. Since the successful integration of
      children and adolescents with a migration background into the KiGGS study brings
      with it a sufficiently large number of cases and since KiGGS covers a wide range
      of health-related topics, comprehensive migration-specific analyses can be
      performed. Thus, KiGGS will contribute to filling some of the current gaps in our
      knowledge of migrant children's health.

PMID- 17514444
TI  - [Consumption of tobacco, alcohol and drugs among adolescents in Germany. Results
      of the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS)].
AB  - Due to its long-lasting effects, the consumption of tobacco, alcohol and drugs is
      one of the central topics of prevention and health promotion in childhood and
      adolescence. The data from the German Health Interview and Examination Survey for
      Children and Adolescents (KiGGS) show that in Germany today 20.5 % of 11-17-year
      old boys and 20.3 % of girls the same age smoke. More than one quarter of
      adolescents who do not smoke themselves are exposed to cigarette smoke several
      times a week; around one fifth are even exposed to it almost every day. In the
      case of alcohol, 64.8 % of boys and 63.8 % of girls have drunk it before. Around
      one third of boys and one quarter of girls indicated that they currently consumed
      alcohol at least once a week. In the last 12 months before the survey 9.2 % of
      the boys and 6.2 % of the girls had taken hashish or marijuana. Other drugs such
      as Ecstasy, amphetamines or speed had been consumed by less than 1 % of the
      adolescents. The use of psychoactive substances rises markedly as children get
      older and is thus the most widespread among 16-17-year-olds. Adolescents of low
      social status smoke more frequently; in the case of alcohol and drug consumption,
      however, no significant status-specific differences are observed. There is also a
      raised prevalence of smoking among boys and girls who attend a secondary school
      and live in the states of the former GDR. The results emphasise the need for an
      addiction prevention programme which should include intervention to prevent
      children taking up substance use, as well as withdrawal treatment.

PMID- 17514445
TI  - [Food consumption of children and adolescents in Germany. Results of the German
      Health Interview and Examination Survey for Children and Adolescents (KiGGS)].
AB  - Since dietary behaviour has an essential impact on health, information on food
      consumption was obtained in the German Health Interview and Examination Survey
      for Children and Adolescents (KiGGS). The average food frequency and portion size
      "in recent weeks" was assessed with a food frequency questionnaire. Two versions
      of the questionnaire, identical in content, exist: one aimed at parents of 1-10
      year-olds and the other directly at 11-17-year-olds. The results include data on
      7,186 boys and 6,919 girls, aged 3-17. About half of the participants each
      consume bread, milk and fresh fruits every day. The majority (about three
      quarter) eat fast food only once a month or less. However, 16 % of the
      participants eat chocolate, and almost 20 % other sweets every day. More boys
      than girls individually consume soft drinks, milk, dairy products, meat, sausage,
      cereals and white bread every day. More girls consume fresh fruits and raw
      vegetables each day. With increasing age the proportion of daily consumers of
      soft drinks, cheese (and among boys also meat and sausage) increases, but the
      proportion of daily consumers of juices, tap water, milk, dairy products, fresh
      fruits, raw vegetables, cookies, chocolate, sweets (and among girls also
      breakfast cereals) falls. As expected the consumption of sweets and soft drinks
      is relatively high. Whereas more than half of the children each consume fruits
      and vegetables on a daily base, this consumption declines with increasing age.

PMID- 17514446
TI  - [Distribution, duration and temporal trend of breastfeeding in Germany. Results
      of the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS)].
AB  - Breast milk is the most natural and best type of nutrition for almost all
      infants. Moreover, breastfeeding is associated with health benefits for mother
      and child: breast milk supports the development of the infant and protects it
      against diseases; the health benefits for the mothers also extend beyond the
      period after birth. Therefore, the WHO recommends exclusive breastfeeding for at
      least six months. Until now, no representative data on the breastfeeding rate
      have been available in Germany. The KiGGS results show an increase in the
      breastfeeding rate from 1986 to 2005. Across all age groups studied, 76.7 % (95 %
      CI: 75.2 %-78.1 %) of the children were ever breastfed. The rate of ever
      breastfed children was significantly lower in mothers from socially disadvantaged
      population groups, children of mothers who had smoked during pregnancy or in
      situations with problems after birth. Children with migration background were
      more frequently ever-breastfed than children without migration background. The
      average duration of breastfeeding was - across all age-groups - 6.9 months (95 %
      CI: 6.8-7.0); the duration of full breastfeeding was 4.6 months (95 % CI: 4.5
      4.7) on average. 22.4 % (95 % CI: 21.4 %-23.5 %) of all children from the KiGGS
      study population were exclusively breastfed for a period of six months. The
      results emphasises the necessity to further promote breastfeeding, especially to
      support the socially disadvantaged, and most of all to encourage a positive
      attitude towards breastfeeding in the society.

PMID- 17514447
TI  - [Physical activity among children and adolescents in Germany. Results of the
      German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS)].
AB  - Regular physical activity has a positive effect on health and wellbeing at any
      age. For this reason, sports and exercise enhancing measures are inherent parts
      of public health in Germany. The German Health Interview and Examination Survey
      for Children and Adolescents (KiGGS) provides a nationally representative
      database which allows a comprehensive analysis of physical activity behaviour
      among young people. This may support the planning and implementation of health
      intervention measures. Primary results of KiGGS indicate that most children aged
      3 to 10 years regularly go in for sports: around three quarters of girls and boys
      go in for sports at least once a week, and even more than one third three times a
      week or more. Children without sport engagement come disproportionately often
      from families with low socioeconomic status, with a migration background or from
      former East Germany. Also among adolescents sports and exercise activity is very
      common. Among 11-17 year olds, how ever, the current recommendation to conduct
      physical and or sports activities on most days of the week is only achieved by
      every fourth boy and every sixth girl. Especially girls with low socioeconomic
      status and with a migration background show a lack of physical activity. These
      results underline the importance of sports- and exercise-promoting measures in
      childhood and adolescence, designed for specific target groups.

PMID- 17514448
TI  - [Use of electronic media in adolescence. Results of the German Health Interview
      and Examination Survey for Children and Adolescents (KiGGS)].
AB  - The use of electronic media is playing an ever greater role in adolescents'
      recreational behaviour. From the point of view of the health sciences, one
      question which arises is the extent to which intensive media use is detrimental
      to physical activity and adolescents' health development. The data from the
      German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS), which were evaluated with a focus on 11-17-year-olds, confirm this heavy
      use of electronic media. However, there are distinct group-specific differences.
      For example, boys spend more time than girls on computers, the internet and games
      consoles, whereas girls more often listen to music and use their mobile phones.
      Watching television and videos is equally popular among girls and boys.
      Adolescents of low social status or a low level of school education use
      electronic media far more frequently and for longer times, especially television
      and video, games consoles and mobile phones. The same is true of boys and girls
      from the former states of the GDR and for boys (but not girls) with a background
      of migration. A connection to physical activity has been established for
      adolescents who spend more than five hours a day using electronic media.
      Moreover, this group of heavy users is more often affected by adiposity. The
      results of the KiGGS study, which are in line with earlier research findings,
      thus demonstrate that the use of electronic media is also of relevance from the
      point of view of public health and should be included in investigations into the
      health of children and adolescents.

PMID- 17514449
TI  - [Oral health behaviour of children and adolescents in Germany. First results of
      the German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS)].
AB  - Despite successful prevention and the possibility to directly control oral health
      by individual behaviour, children are still affected by caries. Aim of this
      article is to determine the prevalence and the social factors influencing
      selected aspects of oral health behaviour based on data of the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS). Over a
      period of three years, 17,641 children and adolescents aged 0 to 17 years - a
      representative sample for Germany - were examined in the nationwide KiGGS study.
      Based on a written survey and a medical interview, data on oral health behaviour
      were also collected. 29 % of the surveyed children and adolescents brushed their
      teeth only once daily or less frequently. This type of teeth brushing behaviour
      shows a social status gradient (low: 39 %, middle: 28 %, high: 22 %) and is more
      frequently found in children with a migration background (45 %) than in those
      without a migration background (26 %). Differences were also found between girls
      and boys (girls: 25 %; boys: 33 %). In only 8 % of cases, parents stated that
      their children have a dental check-up less than once a year. However, this
      information substantially differs from the actual visits to dentists. Here again,
      differences regarding social status (low: 12 %; high: 6 %) and migration status
      (migrants: 16 %; non-migrants: 6 %) were found. According to the parents, 43 % of
      the 0-to-2-year-olds and 7 % of the 3-to-6-year-olds use pharmaceutical
      preparations for caries prevention. Relevant differences were found between
      migrants (5 %) and non-migrants (8 %). These results show that there is primarily
      a need for social status-specific and culture-specific prevention. To identify
      starting points for effectively offering preventative measures, a systematic
      study into the factors causing these behavioural differences is needed.

PMID- 17514450
TI  - [Body measurements of children and adolescents in Germany. Results of the German
      Health Interview and Examination Survey for Children and Adolescents (KiGGS)].
AB  - In the nationwide German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS), a number of anthropometric parameters were assessed in a
      standardised way in 17,641 boys and girls. To this end, body weight and height,
      head circumference and upper arm length, as well as two skinfold thicknesses
      (triceps, subscapular) were measured for the entire age range (0-12 years);
      starting from 6 years of age, elbow breadth and from 11 years of age waist and
      hip circumference were measured in addition. For all parameters, means with
      confidence intervals are reported per age (in years) and gender. Median graphs
      depict the changes with increasing age according to gender for each body
      measurement. The complex age-related anthropometric developments along with
      significant gender specificity show the full range of the dynamic physical
      development in boys and girls. Based on skinfold measurement data, the body fat
      percentage was estimated. Thickness and location of the skinfolds, as well as the
      calculated waist-to-hip ratio is used as an indicator for gender-specific fat
      distribution. Using the frame index, it is attempted to estimate skeletal
      robustness. For the anthropometric parameters studied, hardly any regional
      differences were found. However, head circumference, frame index and all
      parameters strongly associated with body fat show a significant social status
      gradient. Children and adolescents with migration background have on average a
      lower height, larger waist circumference and higher percentage of body fat.

PMID- 17514451
TI  - [Perinatal risk factors for long-term health. Results of the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS)].
AB  - KIGGS is a health survey on 17,641 children and adolescents in 167 communities
      representative for Germany, conducted between May 2003 and May 2006. Of the
      perinatal indicators, only a small proportion of data important for long-term
      outcomes was available for statistical analysis, and is presented here. In the
      past 20 years the mean weight gain during pregnancy has increased significantly
      by 2 kg, the mean birth weight has increased significantly by an average of 50 g,
      there has been no significant time trend for smoking and alcohol consumption in
      pregnancy. Birth weight and pregnancy weight gain of the mother correlate
      significantly. Pregnancy weight gain explains 5% of the birth weight in first
      born infants. 17-18% of the mothers smoked during pregnancy, 4 times as many in
      the lower than the upper social class. 14% of the mothers consumed alcohol in
      pregnancy, but only 1% regularly. Only 5% of the migrants, but 3 times as many of
      the non-migrants consumed alcohol in pregnancy, and 2 1/2 times as many of the
      upper class compared to the lower class. With respect to smoking and alcohol
      consumption during pregnancy there seems to be an urgent need for political
      action.

PMID- 17514452
TI  - [Sexual maturation of children and adolescents in Germany. Results of the German
      Health Interview and Examination Survey for Children and Adolescents (KiGGS)].
AB  - Following the standstill in maturity acceleration in the eighties of the
      twentieth century, now a further shift in maturity development towards younger
      ages is the issue of an international and also German discussion. The collection
      of sexual maturity data in boys and girls as part of the nationwide German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS) is intended
      to pro vide population-representative information on sexual maturation and to
      evaluate associations between maturity status and selected health and social
      data. Girls were interviewed regarding their first menstrual period (menarche)
      and boys regarding voice change (status-quo method). Pubic hair was self-assessed
      by children and adolescents from 10 to 17 years of age, based on drawings of
      Tanner's defined developmental stages. The median age for menarche, for voice
      change and pubic hair stages were calculated using a logit model. At an age of 10
      years, 42.4 % of girls and 35.7 % of boys report the development of pubic hair.
      At 17 years of age, the majority of girls and boys have reached the stages PH5
      (girls 57.5 %, boys 47.8 %) and PH6 (girls 23.6 %, boys 46.5 %) according to
      Tanner. The average age for each pubic hair stage is lower in girls (PH2 10.8;
      PH3 11.7; PH4 12.3; PH5 13.4 years) than in boys (PH2 10.9; PH3 12.6; PH4 13.4;
      PH5 14.1). The median age at menarche is 12.8 years, the median for voice change
      (voice low) 15.1 years. Significant differences in age at menarche are found in
      girls depending on socioeconomic status (12.7/12.9/13.0 years for low/middle/high
      status) and between girls with and without migration background (12.5/12.9
      years). No differences in age at menarche can be seen between East and West
      Germany or cities and rural areas. The association between maturity status and
      BMI is more pronounced in girls than in boys. Overall, the onset of maturity
      development in German children and adolescents is not significantly earlier than
      in other European studies.

PMID- 17514453
TI  - [Prevalence of somatic diseases in German children and adolescents. Results of
      the German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS)].
AB  - In the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS), which was conducted from 2003 to 2006, data on
      acute/infectious and chronic diseases were collected from a population-based
      sample of 17,641 subjects aged 0 to 17 years. The annual prevalence rates among
      acute diseases vary widely. Children and adolescents are most frequently affected
      by acute (infectious) respiratory conditions. 88.5 % of the surveyed children and
      adolescents experienced at least one episode of common cold within the last 12
      months. Among the other acute respiratory infections, bronchitis and tonsillitis
      were the most frequently encountered conditions with 19.9 % and 18.5 %,
      respectively. The 12-month prevalence of otitis media and pseudocroup was 11 %
      and 6.6 %, respectively. 1.5 % of the children and adolescents experienced an
      episode of pneumonia. Apart from respiratory infections, gastrointestinal
      infections were very frequently stated as reasons for acute illness. Furthermore,
      12.8 % of the children and adolescents experienced a herpetic infection, 7.8 % a
      conjunctivitis and 4.8 % a urinary tract infection. Lifetime prevalence rates of
      infectious diseases were as follows: pertussis 8.7 %, measles 7.4 %, mumps 4.0 %,
      rubella 8.5 %, varicella 70.6 %, scarlet fever 23.5 %. The various chronic
      somatic diseases in children and adolescents had different lifetime prevalence
      rates. Most frequently, children and adolescents were affected by obstructive
      bronchitis (13.3 %), neurodermatitis/atopic eczema (13.2 %) and hay fever (10.7
      %). Scoliosis and asthma had been diagnosed by a doctor in 5.2 % and 4.7 % of
      subjects aged 0-17 years, respectively. The lifetime prevalence rates of the
      remaining diseases varied between 0.14 % for diabetes mellitus and 3.6 % for
      convulsions/epileptic fits. For the first time ever, these survey results provide
      nationwide representative information on the prevalence rates of acute/infectious
      and chronic diseases in children and adolescents which is based on a population
      representative sample.

PMID- 17514454
TI  - [Allergic diseases. Results from the German Health Interview and Examination
      Survey for Children and Adolescents (KiGGS)].
AB  - In the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS) from 2003-2006 information was collected on allergic diseases
      (asthma, atopic dermatitis, hay fever, allergic contact eczema) from a population
      based sample of 17,641 0-to 17-year-olds, and blood samples were studied for
      specific IgE antibodies to 20 common allergens. The lifetime prevalence (LTP) of
      at least one atopic disease was 22.9 % (95 % CI: 22.0-23.7 %), the 12-month
      prevalence (12MP) was 16.1 % (15.4-16.8 %); boys (17.3; 16.3-18.2 %) were more
      frequently affected than girls (14.9; 14.0-15.8 %). Children with a background of
      migration were less often currently affected by an atopic disease, as were
      children from families of low social status. According to parents' accounts, the
      LTP of allergic contact eczema was 9.9 % (9.4-10.5 %); girls (13.8;12.9-14.8)
      were more frequently affected than boys (6.2; 5.6-6.9 %). Of the 3- to 17-year
      olds, 40.8 % (39.6-42.0 %) were sensitised to at least one of the allergens
      tested; boys (45.0; 43.5-46.5 %) more frequently so than girls (36.4; 35.0-37.9
      %). In the states of the former FRG, the LTP of allergic contact eczema was
      higher (10.2; 9.6-10.9 %) than those in the former GDR (8.4 % 7.4-9.6 %);
      otherwise there were no East-West differences. The KiGGS data provide the first
      nationally representative data on allergic diseases and sensitisation. The
      differences in prevalence observed correspond to a great extent with previous
      studies and may support the hygiene hypothesis. The prevalences in East and West
      Germany now seem to have equalised.

PMID- 17514455
TI  - [Pain in children and adolescents in Germany: the prevalence and usage of medical
      services. Results of the German Health Interview and Examination Survey for
      Children and Adolescents (KiGGS)].
AB  - As part of the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS), representative data were collected on pain in 14,959
      children and adolescents aged 3 to 17 years in Germany. The results are reported
      separately for 11-17-year olds, who were asked themselves, and 3-10 year olds,
      whose parents reported on their pain. Among the 3-10 year olds, the prevalence of
      pain over three months was 64.5% and among the 11-17 year olds it was 77.6%
      (71.1% altogether for the 3-17 year old children). Pain prevalence increased
      significantly with age; in all age groups girls reported pain significantly more
      often than boys of the same age. In the 3-10 year olds the most common pain
      localisation was stomach pains, followed by pain in the head and throat. Children
      and adolescents aged 11 to 17 most often reported headaches, followed by pains in
      the stomach and back. Pain occurring at least once a week in the last three
      months was reported by 24.3% of the 11-17 year old children and adolescents and
      by 9.9% of the 3-10 year old children suffering from pain. More than half (54.1%)
      of the 3-10 year olds and more than one third of the 11-17 year olds (35.9%) who
      reported recurrent principal pain consulted a doctor for this reason; 36.7% and
      46.7% respectively took medicine. These results show that pain is a relevant
      problem in children and adolescents in Germany.

PMID- 17514456
TI  - [Injuries among children and adolescents (1-17 years) and implementation of
      safety measures. Results of the nationwide German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS)].
AB  - Parent interviews with regard to their children's accidents and to accident
      protective measures in the Health Interview and Examination Survey for Children
      and Adolescents (KiGGS) aimed at extending our knowledge of age- and gender
      specific injuries and to identify risk groups and risk factors for injury
      prevention. The parents of 16,706 children (aged 1-17 years) were asked about
      their children's injuries within the last 12 months which were medically treated,
      and about accident mechanisms, consequences of injuries, and ambulatory and
      hospital treatment. In addition, parents and children aged 11 to 17 years (n =
      6813) were asked to give information on protective measures. According to the
      parents 15.9 % of the children had at least one injury within the last 12 months,
      15.2 % because of an accident and 0.8 % because of assault. In the age group 1-17
      boys have been injured significantly more often than girls (17.9 % vs. 14,0 %).
      Overall, 13.3 % of 2,410 injured children and adolescents were hospitalized. Two
      thirds of the accidents among toddlers were domestic accidents (60 %) whereas
      leisure and sport accidents were most prevalent in children and adolescents aged
      5-14 years and 15-17 years (32.1 % and 38.9 %). The proportion of accidents in
      child care facilities and educational institutions tripled from infancy to school
      age (age 5-14 years) (10.9-28.7 %), as did traffic accidents (5.6-16.7 %). The
      three most frequent injury mechanisms in the age range 1-17 years were falls on
      level ground (35.2 %), falls from heights (25.2 %) and collisions with objects or
      persons (20.6 %). Falls from heights showed the highest risk in toddlers (35.8
      %). Contusions, sprains and strains increased to a highest level of 50.9 % in
      adolescents; likewise, bone fractures increased from 10.7 % in toddlers to 21.8 %
      in adolescents aged 15-17 years. An influence of socioeconomic status on injuries
      overall and on consequences of injuries was not seen. For traffic accidents in
      children aged 1-17 years boys (p = 0.019) and girls (p = 0.047) from families
      with lower socioeconomic status showed higher rates of accidents than children
      from families with higher socioeconomic status. The application of protective
      measures was lowest in the age group 14-17 years. While according to the parents
      about 90 % of children aged 3-4 years wear a helmet when riding a bicycle or when
      skating, this quote was lower in the age group 5-14 (60 %) and dropped to about
      15 % in the age group 14-17 (about 15 %). Also the rate for using protective
      clothes was lowest in age group 14-17 (boys 41.8 %; girls 52.2 %). In children
      and adolescents the rate of self-reported helmet use is lower than estimated by
      their parents. In all age groups migration background and low socioeconomic
      status were associated with lower use of protective measures (helmets and
      protective clothes). The age related data analysis should be the starting point
      in prevention measures for specific risk groups considering migration and
      socioeconomic status. Prevention activities in traffic should focus on families
      with low social status. Adolescents should be specifically and adequately
      addressed regarding the benefits of certain safety measures when riding a bicycle
      and when skating.

PMID- 17514457
TI  - [Blood pressure measurement in the German Health Interview and Examination Survey
      for Children and Adolescents (KiGGS). Methodology and initial results].
AB  - Hypertension is one of the main risk factors for cardiovascular disease and ranks
      among the leading causes of morbidity and mortality worldwide. Hypertension in
      children is rare, but the blood pressure rank in relation to peers is often
      maintained from childhood into adulthood and is therefore of great public health
      relevance. For this reason, one of the aims of the German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS) was to collect
      representative data on blood pressure in children aged 3 to 17 years, in order to
      create an epidemiological basis for a comprehensive analysis of blood pressure in
      children and adolescents in Germany. Two oscillometric blood pressure
      measurements were obtained using an automated device (Datascope Accutorr Plus)
      and two readings of systolic, diastolic and mean arterial pressure and of heart
      rate were obtained in a standardised fashion in 14.730 children (7203 girls and
      7527 boys). The main aim of this article is a detailed description of the blood
      pressure measurement in KiGGS, which is important for the interpretation of our
      findings compared to other studies. Our initial results on the distribution of
      systolic and diastolic blood pressure confirm previous findings of increasing
      blood pressure with age and height and of higher systolic blood pressure levels
      among boys compared with girls from the age of 14 years.

PMID- 17514458
TI  - [The prevalence of overweight and obese children and adolescents living in
      Germany. Results of the German Health Interview and Examination Survey for
      Children and Adolescents (KiGGS)].
AB  - Overweight and obesity are an increasing problem: worldwide, for Germany and for
      children and adolescents. Until now there have been no representative and age
      specific assessments of the prevalence of obesity among children and adolescents
      in Germany. Thus, the standardised height and weight measurements gathered in the
      German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS) have, for the first time, provided national, representative data about
      overweight and obesity in young people. The terms 'overweight' and 'obese' are
      defined based on percentiles of the body mass index (BMI) of the Kromeyer
      Hauschild reference system. Of children and adolescents between the ages of 3 and
      17, 15% exceed the 90th BMI percentile of the reference data and are thus
      overweight, 6.3% exceed the 97th BMI percentile and thus suffer from obesity by
      this definition. The proportion of overweight rises from 9% of 3-6-year-olds to
      15% of 7-10-year-olds and 17% of 14-17-year-olds. The prevalence of obesity is
      2.9%, 6.4% and 8.5% for the same age groups respectively. No clear differences
      between boys and girls or between East and West Germany are detected. Children
      are at a higher risk of being overweight or obese if they have a lower
      socioeconomic status, have a migration background, or have mothers who are also
      overweight.

PMID- 17514459
TI  - [Iodine intake in Germany. Results of iodine monitoring in the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS)].
AB  - Iodine is an essential trace element which is found in too low quantities in the
      soil in Germany. The resulting iodine deficiency in human beings is countered by
      iodine prophylaxis, essentially consisting of iodised table salt and the
      iodisation of agricultural animal feed. In iodine monitoring during the German
      Health Interview and Examination Survey for Children and Adolescents (KiGGS), the
      thyroid volumes of all children and adolescents from six years of age were
      determined using sonography. To assess iodine intake among the population, iodine
      excretion in the urine was also measured. The median ioduria value was 117
      microg/l, putting it at the lower end of the scale of 100-200 microg/l
      recommended by the World Health Organisation. It can be concluded from these
      results that the iodine prophylaxis has been successful and that iodine intake
      has improved compared with the past. In accordance with the WHO recommendations
      there is no iodine deficiency in Germany any more; however, at the same time the
      population's iodine intake is at a relatively low level. The aim is at least to
      keep up what has been achieved, meaning that measures to improve iodine intake
      must not be allowed to slacken.

PMID- 17514460
TI  - [Prevalence and characteristics of children and youth with special health care
      needs (CSHCN) in the German Health Interview and Examination Survey for Children
      and Adolescents (KiGGS)].
AB  - In order to arrive at population-based estimates on the prevalence and
      characteristics of children and adolescents with specific health care needs
      (CSHCN), screening instruments focussing on the consequences of physical, mental
      and behavioral problems rather than on medical diagnoses have been developed. One
      of the most feasible and widely tested instruments, the CSHCN screener was added
      to the self-administered questionnaire for parents of children participating in
      the German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS). The overall weighted prevalence of CSHCN was 16.0% among boys and 11.4%
      among girls. Children at kindergarten or school age were more than 2-3 times more
      likely to screen positive compared to toddlers. Up to 14 years, the sex
      difference persisted through all age groups and was most pronounced between the
      ages of 3 and 10 years. Children with a migrant background had significantly
      lower rates of CSHCN compared to non-migrants. This was particularly true for
      boys (8.0% vs. 17.1%). CSHCN status was not related to social status,
      urbanization or residence in former West vs. former East Germany. Except for the
      lack of association with social status, these results are in good accordance with
      observations from the US National Survey of CSHCN.

PMID- 17514461
TI  - [Biochemical measures in the German Health Interview and Examination Survey for
      Children and Adolescents (KiGGS)].
AB  - In the framework of the German Health Interview and Examination Survey for
      Children and Adolescents (KiGGS) a variety of biochemical parameters was
      determined in order to provide objective information on health status and
      particular health risks, in addition to parent interview data and anthropometric
      measurements. Overall 43 parameters covered three areas of particular public
      health interest: micronutrient deficiency, seroepidemiology of infectious
      diseases and immunization status, and risk indicators or risk factors for chronic
      non-communicable diseases. A review of available evidence regarding valid
      reference or cutoff values as well as the standardization of laboratory methods
      led to the categorization of these parameters into five classification
      categories. Here, we discuss the present first descriptive results on selected
      parameters representing the various categories. In order to determine the public
      health impact of measurement results, and perhaps even derive normative reference
      data relevant to health care, more detailed analyses will be required. In the
      first step, these will focus on cross-sectional analyses of the association
      between biochemical parameters and other health-related anthropometric and
      sociodemographic variables. Intermediate and long-term objectives will include
      the construction of multidimensional reference values taking into account several
      laborato ry data and other clinical information at the same time, and the
      prognostic validation of reference or cut-off values based on a follow- up of the
      study participants for clinical outcomes.

PMID- 17514462
TI  - [The German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS): state of immunity against poliomyelitis in German children].
AB  - One of the goals of the WHO is the worldwide eradication of poliomyelitis in the
      coming years. Europe was declared poliofree in 2002, but increasing migration may
      lead to a come-back of circulating polioviruses. A high level of population
      immunity protects against imported wild viruses from endemic areas. The first
      seroprevalence data since the switch from live to inactivated vaccine in Germany
      (OPV to IPV) are provided. A serum panel was tested (n=2,046) in order to study
      the serological status against poliomyelitis. The microneutralization test on RD
      cells was used. Overall, neutralizing antibodies against poliovirus types 1, 2
      and 3 were detected in 97.4%, 97.6%, and 93.6% of samples, respectively. Of the
      test persons, 91.7% had antibodies against all three virus types. Only 26
      children simultaneously lacked neutralizing antibodies for all three serotypes
      (1.3%). No significant correlation between gender, region (East/West)), migration
      status (with/without migration background) and antibody prevalence to
      polioviruses was found. The seroprevalence of antibodies against all three types
      of polioviruses indicates a very high level of population immunity in German
      children. It must be maintained through consequently performed vaccination
      programmes.

PMID- 17514463
TI  - [Motor Fitness. Results of the German Health Interview and Examination Survey for
      Children and Adolescents (KiGGS)].
AB  - Motor fitness was investigated in children and adolescents aged 4-17 using
      specific short tests. These tested the motor abilities: co-ordination, strength,
      cardiorespiratory fitness and flexibility. Among the 4-10 year olds, the focus of
      the investigation was on recording coordination, strength and flexibility; in the
      age group of the 11-17 year olds it was on recording cardiorespiratory fitness.
      The current investigation describes motor fitness based on the tested abilities
      according to age, sex and sociodemographic aspects. In all the test tasks, as
      expected, there are better results from older children and adolescents than from
      younger ones. Among the 4-10 year olds, girls display a slightly higher motor
      fitness in five out of the six tasks. In cardiorespiratory fitness, the cycle
      ergometer test for the 11-17 year olds shows better results for boys. The results
      indicate that there is a correlation between migrant status, social status and
      motor fitness. The shown differences point out that possible intervention
      programmes should be specifically attuned to age and sex as well as to the
      concerns of children and families with a migrant background and those of low
      social status. These collected data on motor fitness produced a database,
      representative of Germany. This will enable statements on state and development
      of motor fitness in children and adolescents in the future.

PMID- 17514464
TI  - [Behavioural problems in children and adolescents. First results from the German
      Health Interview and Examination Survey for Children and Adolescents (KiGGS)].
AB  - Mental health problems in children and adolescents constitute health impairments
      with major implications regarding individual wellbeing as well as daily and
      social functioning. In addition, these problems often burden the social partners
      of the individual. Within the German Health Interview and Examination Survey for
      Children and Adolescents (KiGGS), the parents of 14478 children and adolescents
      aged 3-17 answered the Strengths and Difficulties Questionnaire (SDQ) which
      assesses behavioral problems and strengths in the areas emotional problems,
      hyperactivity, behavioral problems, peer problems and prosocial behavior.
      According to the results of the Total Difficulties Score (SDQ) 11,5 % girls (G)
      and 17,8 % boys (B) are classified borderline or abnormal, respectively. 92,5 %
      (G) and 86,3 % (B) display an adequate pro social behavior. Most prevalent
      problem areas are behavioral problems (G = 11,9 %, B = 17,9 %), emotional
      problems (G = 9,7 %, B = 8,6 %) and hyperactivity problems (G = 4,8 %, B = 10,8
      %). The test-data of approximately 8,1 % of the respondents with high socio
      economic status (SES), 13,4 % of those with middle SES and 23,2 % of those with
      low SES hinted at mental health problems. Migrants are more frequently affected
      than non-migrants. Results point at the need for early detection and prevention
      of commencing mental health problems. Especially the noneasily accessible groups
      like those with low socioeconomic status or migrants have to be considered.

PMID- 17514465
TI  - [Eating disorders in children and adolescents. First results of the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS)].
AB  - Eating disorders are included in the category of mental and behavioural disorders
      (ICD 10). They are among the most common chronic health problems encountered in
      children and adolescents. A total of 7,498 children and adolescents (weighted)
      aged 11 to 17 years answered the SCOFF questionnaire, a screening instrument to
      identify cases of suspected eating disorder. Parallel to the SCOFF questionnaire,
      further factors for possible eating disorders, such as the Body Mass Index (BMI),
      information on abnormal behaviour (using the Strengths and Difficulties
      Questionnaire, SDQ) smoking, sexual and body self-image assessment, were gathered
      to substantiate the results. In total, 21.9 % of the children and adolescents in
      Germany aged 11 to 17 years showed symptoms of eating disorders. With 28.9%,
      girls are more frequently affected than boys (15.2 %); this difference is highly
      significant. In the presence of almost identical initial values, the rate of
      subjects with abnormal SCOFF scores increases, starting from age 11 years, in
      girls as they age, while it drops in boys. Children and adolescents with low
      socioeconomic status (SES) are, with 27.6 %, almost twice as often affected than
      those with high SES (15.6 %). Migrants have an approx. 50 % higher rate compared
      to non-migrants. A 2.5-fold increase in the percentage of individuals with normal
      weight who perceive themselves as too fat is found among those with abnormal
      SCOFF scores. Individuals with abnormal SCOFF scores smoke more and report more
      frequently about sexual harassment. Because of the severity, the tendency to
      chronification and the protracted therapy of the clinically apparent disorders,
      effective concepts for prevention should be developed.

PMID- 17514466
TI  - [The German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS): risks and resources for the mental development of children and
      adolescents].
AB  - Along with the salutogenetic approach in health sciences, the quest for factors
      exerting a protective effect on mental development and health has increasingly
      gained importance, complementing the study of risk factors. A total of 6,691
      children and adolescents aged 11 to 17 years answered questionnaires on personal,
      social and family resources as part of the German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS). Children with low
      socioeconomic status (SES) more frequently show deficits in their personal,
      social and family resources. Similarly, in children with migration background a
      higher percentage with poorly developed personal and social protective factors is
      found. Older children report less family resources but more social resources than
      younger children; in comparison to boys, girls have more social but less personal
      resources at their disposal. Clear connections are observed between protective
      factors and health-related risk-taking behaviour. Deficits in personal and family
      resources are associated with an increased risk for smoking. Although an
      increased percentage of smoking and alcohol consuming children and adolescents is
      found to be associated with well-developed social resources, the risk for drug
      experiences is not increased. The results prove the necessity to build up
      protective factors as a preventative measure. Especially in children and
      adolescents with weak protective factors, an increased risk of mental health
      problems can be expected in the presence of stressful events.

PMID- 17514467
TI  - [Health-related quality of life of children and adolescents in Germany. Norm data
      from the German Health Interview and Examination Survey (KiGGS)].
AB  - This study investigates the health-related quality of life of children and
      adolescents in Germany, using the internationally employed KINDL-R questionnaire
      for measuring the health-related quality of life of children and adolescents. In
      the National Health Interview and Examination Survey for Children and Adolescents
      (KiGGS) the parents of 14,836 children and adolescents aged 3-17 years completed
      the KINDL-R, as well as 6,813 children and adolescents (11-17 years old). The
      reliability (Cronbach's alpha = 0.85) and validity of the measurements using the
      KINDL-R were confirmed. The differences in health-related quality of life of
      children and adolescents from different social backgrounds and with different
      health statuses, which were to be expected on theoretical grounds, were
      demonstrated by the KINDL-R scores (size of effect "d" up to 1.52). The means and
      percentiles were calculated for the total sample as well as stratified by age
      group, sex, geographical region (East/West), migratory status and socio-economic
      status. The results of this study can be used as representative, normative data
      for the population of children and adolescents in Germany in general, as well as
      stratified for sociodemographic and socio-economic subpopulations, in order to
      interpret test scores on health-related quality of life (KINDL-R).

PMID- 17514468
TI  - [Children's and adolescents' experiences of violence based on subjective self
      reporting. First results of the German Health Interview and Examination Survey
      for Children and Adolescents (KiGGS)].
AB  - Experiences of violence in childhood and adolescence are connected with
      potentially serious consequences for physical and psychological health. Children
      and adolescents can experience violence as the perpetrator, the victim or the
      perpetrator/victim. As part of the German Health Interview and Examination Survey
      for Children and Adolescents (KiGGS) 3382 boys and 3237 girls answered questions
      on the prevalence of experiences of violence over 12 months, divided into
      experiences as a perpetrator and as a victim. There were also questions on
      people's views on the propensity to instrumental and expressive violence.
      Altogether, 82.5% of girls (G) and 67.2% of boys (B) had not been involved in an
      act of violence in the last 12 months. 19.6% (B) and 9.9% (G) had been
      perpetrators; 5.2% (B) and 3.9% (G) had been victims and 7.6% (B) and 3.6% (G)
      had been perpetrators/victims of an act of violence. The amount of violence
      suffered by respondents with a high socioeconomic status (SES) was the lowest,
      with 81.0% never having been involved in acts of violence, compared with those
      with a lower SES (68.3%) and a medium SES (76.4%). Pupils at Hauptschule (school
      at lower secondary level providing a basic general education) and Gesamtschule
      (comprehensive school) as well as adolescents with a migrant background are more
      often affected by experiences of violence and have more permissive attitudes
      towards violence than those at Gymnasium (high school) or Realschule (school at
      lower secondary level providing more extensive general education) and children of
      non-migrants. Social disadvantage and a migrant background are associated with
      adolescents having more exposure to and a higher propensity for violence.
      Intervention programmes and improvements to basic social conditions may have a
      preventative effect. As no distinction can be made between familial violence and
      other forms of violence using the KiGGS data, care should be taken in
      interpreting it. Its significance lies in identifying risk groups.

PMID- 17514469
TI  - [The prevalence of attention-deficit/hyperactivity disorder (ADHD) among children
      and adolescents in Germany. Initial results from the German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS)].
AB  - The cardinal symptoms of attention-deficit/hyperactivity disorder (ADHD) are
      inattention, hyperactivity and impulsivity. Etiologically, ADHD is mainly put
      down to genetic causes; it entails a considerable range of psychosocial problems
      for those affected and their social environment. The parents of a total of 7,569
      boys (B) and 7,267 girls (G) aged 3-17 who took part in the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS) answered a
      self-administered questionnaire including an ADHD diagnosis question and the
      Strengths and Difficulties Questionnaire (SDQ). In addition behavioural
      observations of 7,919 children (aged 3-11) were carried out during the medical
      and physical tests. Participants whose parents reported that they had ever been
      given an ADHD diagnosis by a doctor or psychologist were classified as ADHD
      cases. Participants were classified as suspected cases of ADHD if they had a
      value of > or =7 on the SDQ inattention/hyperactivity scale. ADHD had ever been
      diagnosed in 4.8 % of the children and adolescents altogether (B: 7.7 %, G: 1.8
      %). Another 4.9 % of the participants can be considered as suspected cases.
      Already 1.8 % of the preschoolers had been given an ADHD diagnosis. At primary
      school age (7-10 years old) the frequency of diagnosis rises sharply. At age 11
      17, ADHD had ever been diagnosed in 1 in 10 boys and 1 in 43 girls. ADHD had been
      diagnosed significantly more frequently among participants of low socio-economic
      status (SES) than among participants of high SES. A diagnosis of ADHD is reported
      less often for migrants, they rank more frequently among the suspected cases. The
      discrepancy between confirmed and suspected cases of ADHD among migrants may
      point to lower diagnosis rates or lower utilization of medical services. The
      short- and long-term medical, social and health-economic effects of ADHD
      illustrate the major public health relevance of the disorder. As for prevention,
      the high share of genetic factors in ADHD etiology primarily suggests secondary
      prevention (early support and early diagnosis) and tertiary prevention measures.
      Further analysis of the KiGGS data could prospectively identify risk groups more
      precisely and refine preventional approaches.

PMID- 17514470
TI  - [Use of medical services. Results of the German Health Interview and Examination
      Survey for Children and Adolescents (KiGGS)].
AB  - The use of operations, visits to doctors and early diagnostic tests for children
      are examples of different services selected from the whole spectrum of
      preventative and therapeutic health service provisions in childhood and
      adolescence. In the German Health Interview and Examination Survey for Children
      and Adolescents (KiGGS), which is representative for Germany, 17,641 children and
      adolescents aged 0-17 or their parents were questioned on subjects such as their
      use of medical services. The use made of individual early diagnostic tests for
      children remains above the 90 % limit until the U7 test and drops to 89.0 % at
      U8, falling to 86.4 % at U9. 81 % of children took part in all the early
      diagnostic tests provided until age 6 (U3 to U9). Another 16 % only took
      advantage of some parts of this service and 3 % of the children never went to one
      of these check-ups. As was to be expected, the annual rate of visits to
      paediatricians drops as children get older from 95.1 % for 0-2-year-olds to 25.4
      % of the 14-17-year-olds, while the rate of visits to general practitioners rises
      from 11.8 % to 53.1 %. If one tracks the rate of visits to specialist doctors all
      the way across childhood and adolescence, different paths emerge: while children
      aged 3-6 most often visit the ear, nose and throat doctor, at primary school age
      they mainly see opticians, and 14-17-year-olds most often visit doctors of
      internal medicine, dermatologists and surgeons. 37.1 % of the 0-17-year-old
      children and adolescents had undergone an operation. In order of declining
      frequency, the operations named were adenoidectomy (15.2 %), tonsillectomy (5.9
      %), herniotomy (3.6 %) and appendectomy (2.4 %). Circumcisions had been carried
      out on 10.9 % of the boys. The different way medical services are used in
      different subgroups may not only depend on medical factors but also on social
      factors, medical attitudes and the availability of services provided.

PMID- 17514471
TI  - [Vaccination coverage and predictors for vaccination level. Results of the German
      Health Interview and Examination Survey for Children and Adolescents (KiGGS)].
AB  - The level of childhood immunisation is an acknowledged indicator for health
      prevention. In Germany, vaccination is not compulsive. Continuous representative
      data derive only from school health examinations. From May 2003 until May 2006
      the German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS) was conducted and vaccination information on 16,460 participants was
      obtained. Using data on the vaccination cards, it was possible to make detailed
      analyses of vaccination coverage in children up to the age of 17. Different
      vaccine types were taken into consideration in defining the term 'immunisation
      coverage'. The average prevalence of full immunisation for tetanus, diphtheria
      und polio as well as the coverage for the first dose of measles, mumps and
      rubella (MMR) vaccination was above 90% in children aged 2-17 years. Vaccination
      coverage for pertussis, Hib and hepatitis B is higher in younger than in older
      age groups. Compliance with the recommendation to have a second MMR dose and to
      make up of hepatitis B and pertussis immunisation is still low, especially in
      adolescents. In 7- to 17-year-old children the additional booster (recommended
      for 5- to 6-year-old children) is frequently missing.

PMID- 17514472
TI  - [Medicine use in children and adolescents. Data collection and first results of
      the German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS)].
AB  - In the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS), data on the current use of medicines during the last 7 days
      prior to the examination were collected from 17,450 subjects aged 0 to 17 years
      by means of a standardised interview conducted by a physician. 50.8 % of all
      children and adolescents reported to have used at least 1 medication. Prevalence
      was found to be highest (74.9 %) in the age group 0 to 2 years. Girls showed with
      53.1% a significantly higher prevalence rate than boys (48.7 %). Children from
      families with low socioeconomic status and children from migrant families stated
      a less frequent use of medication compared to children from families with higher
      socio economic status and no migration background. Most frequently, the boys and
      girls used medicines for the treatment of respiratory tract conditions (ATC code
      R00: 16.8%). This was followed by Alimentary System and Metabolism (ATC code A00:
      16.0%) and Dermatological Preparations (ATC code D00: 9.7%). The most frequent
      indications included with 12.4% of all medicines reported Other Specified
      Prophylactic Measures (ICD code Z29.8), with 11% Acute Rhinopharyngitis (ICD code
      J00), and with 10. 9 % Cough (ICD code R05). Most of the drugs named were
      prescribed by a doctor (58%), one quarter (25%) was independently bought without
      prescription, 14% came from other sources, including the medicine chest, and 2%
      were prescribed by a non-medical practitioner. Regarding the duration of use,
      short-term use (less than 1 week: 55%) was encountered most frequently, while a
      duration of use of at least one year was reported for 13% of all medicines named.
      The results presented here describe the key points of medicine use among children
      and adolescents in Germany and are representative for this population segment.
      Based on the extensive data collected, further aspects, such as co- and multi
      medication, are addressed. In addition, special drug segments of public health
      interest shall be represented in the future.

PMID- 17514473
TI  - [Mental health of children and adolescents in Germany. Results from the BELLA
      study within the German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS)].
AB  - The Mental Health Module (BELLA study) examines emotional well-being and
      behaviour in a representative sub-sample of 2,863 families with children aged 7
      to 17 from the National Health Interview and Examination Survey for Children and
      Adolescents (KiGGS). The prevalence of mental health problems was determined
      using the Strengths and Difficulties Questionnaire (SDQ) and additional
      standardised screening measures. Of children and adolescents, 21.9 % (95 %CI:
      19.9-24.0) showed signs of mental health problems. The psychiatric disorders
      observed included anxiety (10.0 %; 95 % CI: 8.7-11.6), conduct disorder (7.6 %;
      95 % CI: 6.5-8.7) and depression (5.4 %; 95 % CI: 4.3-6.6). Of the risk factors
      examined, adverse family climate and low socioeconomic status stand out
      particularly as negative contributors. When several risk factors occur
      simultaneously, the prevalence of mental health problems increases markedly.
      Conversely, positive individual, family and social resources coincide with an
      absence of mental health problems. Children and adolescents with mental health
      problems display distinctly impaired health-related quality of life, and far from
      all of them are receiving treatment. Identifying high risk groups therefore
      requires the assessment of available resources in addition to the usual risk
      factors for mental and subjective health. Strengthening these resources should be
      a key objective, both in prevention and in interventions.

PMID- 17514474
TI  - [The module "Motorik" in the German Health Interview and Examination Survey for
      Children and Adolescents (KiGGS). Motor fitness and physical activity of children
      and young people].
AB  - Motor fitness and physical activity are important aspects of a healthy
      development in childhood and adolescence. However, the assessment of motor
      fitness and physical activity is not subject to standardized criteria;
      furthermore, the samples investigated do not provide a representative image of
      the whole population. Therefore, the existing data only allow very limited
      statements on the state and development of motor fitness and physical activity.
      The "Motorik" module, as part of the German Health Interview and Examination
      Survey for Children and Adolescents (KiGGS), offers nationwide representative
      data on the motor fitness and physical activity of children and adolescents for
      the first time. Besides the baseline-analysis, another aim is to analyse the
      complex relationship between motor fitness, physical activity and health. Motor
      fitness, based on the systematisation of motor abilities, was assessed using a
      test profile. The test profile consists of 11 items measuring cardiorespiratory
      fitness, strength, coordination and mobility. Physical activity was assessed
      using a questionnaire containing 51 items on the duration, intensity and
      frequency of physical activity in everyday life, during leisure time, at school
      and in sports clubs. The above-mentioned questionnaire subtopics were
      supplemented by questions on the weekly prevalence of at least 60 minutes of
      daily physical activity, on material and local conditions, as well as on
      cognition and motivation for physical activity. In the years 2004 to 2006, the
      motor fitness and physical activity of 4,529 children and young people between
      the ages of 4 and 17 years was investigated on 168 sample points in the context
      of the "Motorik" module. Half of the children and adolescents investigated belong
      to the middle class, approximately 15% have a background of migration. The
      majority of the subjects come from small towns, about a quarter live in the city,
      less than 20% are settled in rural areas.

PMID- 17514475
TI  - [German Environmental Survey for Children (GerES IV) in the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS). First
      results].
AB  - The German Environmental Survey for Children (GerES IV) is the environment
      related module of the German Health Interview and Examination Survey for Children
      and Adolescents (KiGGS) of the Robert Koch Institute and the fourth GerES of the
      Federal Environment Agency. The main objective of GerESs is to analyse and
      document the extent, distribution and determinants of exposure to environmental
      pollutants of the German general population. GerES IV was performed from 2003 to
      2006. A total of 1.790 children aged 3-14 years from 150 sampling locations
      participated in GerES IV. Samples of blood, urine, tap water, house dust and
      indoor air were analysed. Hearing tests, measurements of traffic noise and
      interviews to get exposure-related information were conducted. First results
      indicate a clear decrease of the exposure to arsenic, lead and mercury. Cotinine
      concentrations in urine can be used to classify the exposure of children to
      environmental tobacco smoke. The examination of the tap water used in the
      subjects' households indicates that in some households the guideline values of
      the German Drinking Water Ordinance were not always met. This is the case for
      nickel, copper and lead which are used as pipe material for domestic plumbing.

PMID- 17514476
TI  - [The federal state module Schleswig-Holstein in the German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS)].
AB  - From August 2004 to June 2005, the Robert Koch Institute conducted the fieldwork
      for the Schleswig-Holstein module of the German Health Interview and Examination
      Survey for Children and Adolescents (KiGGS). The KiGGS study is a nationwide
      representative survey of the health of children and adolescents aged 0 to 17
      years. By increasing the sample size in the age group 11 to 17 years in Schleswig
      Holstein, the module study generated information which is representative for this
      federal state. For this end, further 18 locations in this federal state were
      included in the module study in addition to the existing 5 study locations in
      Schleswig-Holstein and a study programme which was slightly reduced compared to
      the core survey was realised. A total of 1,931 subjects were examined in
      Schleswig-Holstein: 1,730 in the federal state module and 201 in the core survey.
      The participation rate was 69.5% in the module study. The percentage of quality
      neutral drop-outs was 4.0%. The federal state module was funded by the Ministry
      of Social Welfare, Health, Family, Youth and Seniors of the Federal State of
      Schleswig-Holstein. The data collected were used for health reporting on a
      federal state level.

PMID- 17514477
TI  - [EsKiMo - the nutrition module in the German Health Interview and Examination
      Survey for Children and Adolescents (KiGGS)].
AB  - In a module of the German Health Interview and Examination Survey for Children
      and Adolescents (KiGGS), the dietary behaviour of 6-17-year-olds was assessed
      from January to December 2006. The study, named EsKiMo (Eating Study as a KiGGS
      Module), was performed by the Robert Koch Institute together with the division of
      nutrition and consumer education at the University of Paderborn. It was funded by
      the Federal Ministry of Food, Agriculture and Consumer Protection. Parents of
      participants younger than 12 years were asked to conduct a 3-day dietary record.
      Participants of 12 years and older were personally interviewed about their eating
      behaviour during the last four weeks using DISHES (Dietary Interview Software for
      Health Examination Studies). In addition, they were asked to fill in the KiGGS
      food frequency questionnaire a second time. Furthermore, all participants were
      asked about their socio-demographic background, leisure time activities,
      supplement use, meals at school, body weight and height. The study will provide
      up-to-date, representative data on the nutrition of children and adolescents in
      Germany. The analyses will include the amounts of foods and food groups consumed
      as well as the nutrient intake. By connecting these nutrition data with other
      health data from KiGGS, comprehensive analyses of relationships between nutrition
      and health are possible.

PMID- 17514479
TI  - Repeated methamphetamine treatment impairs spatial working memory in rats:
      reversal by clozapine but not haloperidol.
AB  - RATIONALE: Although chronic use of methamphetamine (METH) leads to long-lasting
      cognitive dysfunction in humans, there are few reports about an animal model that
      reflects METH-induced impairment of working memory. OBJECTIVES: In this study, we
      investigated the effect of repeated METH treatment on spatial working memory in
      rats. MATERIALS AND METHODS: Rats were repeatedly administered METH (2 mg/kg)
      once a day for 7 days, and their memory function was assessed with a delayed
      spatial win-shift task in a radial arm maze. The task consisted of two phases, a
      training phase and a test phase, separated by a delay. RESULTS: METH-treated
      animals showed an impairment of performance in the test phase when the delay time
      was increased from 5 to 30 min or longer. The effect of METH persisted for at
      least 14 days after the drug withdrawal. METH-induced impairment of working
      memory was reversed by clozapine (3 and 10 mg/kg, for 7 days), but not
      haloperidol (1 and 2 mg/kg, for 7 days). The improving effect of clozapine
      diminished 7 days after the withdrawal. Phosphorylated extracellular signal
      regulated kinase1/2 (ERK1/2) levels were significantly increased in the
      hippocampus of saline-treated control rats from 5 to 60 min after the training
      phase. In contrast, hyperphosphorylation of ERK1/2 was abolished in the
      hippocampus of rats treated with METH. CONCLUSIONS: These findings suggest that
      repeated METH treatment induces impairment of working memory, which is associated
      with a dysfunctional ERK1/2 pathway in the hippocampus. Furthermore, clozapine
      may be effective for the treatment of METH-induced cognitive dysfunction.

PMID- 17514481
TI  - The life cycle of Mesostephanus indicum Mehra, 1947 (Digenea: Cyathocotylidae).
AB  - The life cycle of the cyathocotylid fluke, Mesostephanus indicum Mehra, 1947
      infecting the pariah kite, Milvus migrans govinda (Accipitridae), is elucidated.
      The species, reported by Mehra (Proc Nat Acad Sci India 17:1-52, 1947) from Buteo
      rufinus rufinus (Accipitridae), was transferred to the genus Prohemistomum by
      Dubois (Rev Suiss de Zool 58:639-691, 1951). However, it is retained in the genus
      Mesostephanus because of the presence of vaginal sphincter and caudal appendage,
      which are the characters of the genus. Its first intermediate host is the
      gastropod snail, Bellamya bengalensis (Viviparidae), which released the
      furcocercous cercariae. The prohemistomulum-type metacercariae encysted in the
      muscle tissues of the freshwater fish Rasbora daniconius and Puntius sophore
      (Cyprinidae), Mystus malabaricus (Bagridae), Heteropneustes fossilis
      (Heteropneustidae), Aplocheilus lineatus (Cyprinodontidae), Etroplus maculatus
      and E. suratensis (Cichlidae), and Pseudosphromenus cupanus (Belontidae).
      Recovery of M. indicum from M. m. govinda forms a new host record, and this is
      the first report of the life cycle of the genus from India.

PMID- 17514480
TI  - Compulsive drug seeking by rats under punishment: effects of drug taking history.
AB  - RATIONALE: Abstinence from drug occurs in human addicts for several reasons,
      including the avoidance of adverse consequences. OBJECTIVES: To explore a model
      of drug use in the face of adverse consequences in rats through intermittent
      punishment of drug seeking and to investigate whether the ability to withhold
      seeking responses depends upon the duration of drug history. MATERIALS AND
      METHODS: Rats were trained under a seeking-taking chained schedule with sucrose
      or cocaine as reinforcer. Pressing the seeking lever gave access to the taking
      lever, and a single press on this lever delivered the reinforcer after which the
      seeking-taking chain recycled. During punishment, half of the seeking links
      terminated with a mild foot shock without access to the taking link. RESULTS:
      After a moderate history of reinforcement, punishment of the terminal response in
      the seeking link suppressed both sucrose- and cocaine-seeking responses. By
      contrast, rats with an extended cocaine history were more resistant to punishment
      than those with a moderate cocaine history. This enhanced resistance to
      punishment was due to a sub-group of rats that showed minimal or no suppression
      of drug seeking. No differences in suppression of sucrose seeking were observed
      in animals with moderate versus extended sucrose histories. CONCLUSIONS: These
      results suggest that an extended drug self-administration history decreases the
      ability of vulnerable rats to suppress their drug seeking.

PMID- 17514482
TI  - Efficacy of contact lens storage solutions against trophozoite and cyst of
      Acanthamoeba castellanii strain 1BU and their cytotoxic potential on corneal
      cells.
AB  - Acanthamoeba is a free-living amoeba causing a potentially blinding infection of
      the cornea. Contact lens wearers are most at risk and account for about 95% of
      cases. We investigated the in vitro effectiveness of 10 contact lens solutions
      against Acanthamoeba castellanii and their cytotoxicity on corneal cells in
      vitro. Contact lens solutions were evaluated for their amoebicidal activities
      using an inverted light microscope. To determine of their cytotoxicity on corneal
      cells, agar diffusion tests were performed. According to the results obtained
      from the tests, AVIZOR Aqua Soft Comfort and Elegance(R) showed the best
      amoebicidal effect on A. castellanii trophozoites. Cysts were still viable after
      overnight (8 h) exposure. In the case of the cyctotoxic acitivities, All In One
      Light, Astek, SOLO-Care Aqua, Maxima, and Horien showed no cytotoxicity on the
      corneal cells. ReNu MultiPlus, AVIZOR Aqua Soft Comfort, Carrera, and Elegance
      showed mild cytotoxicity on the corneal cells. Plurisol.M presented moderate
      cytotoxicity on the corneal cells. All commercial solutions examined in this
      study are the lack of efficacy against A. castellanii. Improvement or development
      of new contact lens disinfecting systems by the manufacturers is needed to
      prevent Acanthamoeba keratitis.

PMID- 17514486
TI  - Estimating the efficiency of fish cross-species cDNA microarray hybridization.
AB  - Using an available cross-species cDNA microarray is advantageous for examining
      multigene expression patterns in non-model organisms, saving the need for
      construction of species-specific arrays. The aim of the present study was to
      estimate relative efficiency of cross-species hybridizations across bony fishes,
      using bioinformatics tools. The methodology may serve also as a model for similar
      evaluations in other taxa. The theoretical evaluation was done by substituting
      comparative whole-transcriptome sequence similarity information into the
      thermodynamic hybridization equation. Complementary DNA sequence assemblages of
      nine fish species belonging to common families or suborders and distributed
      across the bony fish taxonomic branch were selected for transcriptome-wise
      comparisons. Actual cross-species hybridizations among fish of different
      taxonomic distances were used to validate and eventually to calibrate the
      theoretically computed relative efficiencies.

PMID- 17514488
TI  - Inhibition of influenza viral neuraminidase activity by collectins.
AB  - The collectins, lung surfactant proteins A and D (SP-A and SP-D), contribute to
      innate host defense against influenza A virus (IAV) in vivo. Although collectins
      bind to the viral hemagglutinin (HA) and inhibit early stages of viral infection
      in vitro, they also bind to the neuraminidase (NA) and inhibit NA activity. We
      used a variety of NA functional assays, viral strains and recombinant (mutant or
      wild type) collectins to characterize the mechanism of NA inhibition. NA
      inhibition by SP-D correlates with binding of its carbohydrate recognition domain
      (CRD) to oligomannose oligosaccharides on the viral hemagglutinin (HA). The
      effects of SP-D are additive with oseltamivir, consistent with differences in
      mechanism of action. NA inhibition was observed using fetuin or MDCK cells as a
      substrate, but not in assays using a soluble sialic acid analogue. Collectin
      multimerization and CRD binding properties are key determinants for NA
      inhibition. SP-D had greater NA inhibitory activity than mannose-binding lectin,
      which in turn had greater activity than SP-A. The markedly greater NA inhibitory
      activity of SP-D compared to SP-A may partly account for the finding that
      deletion of the SP-D gene in mice has a greater effect on viral replication in
      vivo.

PMID- 17514489
TI  - Partial characterisation of five cloned viruses differing in pathogenicity,
      obtained from a single isolate of pigeon paramyxovirus type 1 (PPMV-1) following
      passage in fowls' eggs.
AB  - Viruses with intracerebral pathogenicity indices (ICPIs) of 0.025, 0.55, 1.013
      and 1.3. were cloned from a PPMV-1 isolate with an ICPI of 0.32 by passage in
      embryonated fowls' eggs. Deduced amino acid sequences of the haemagglutinin
      neuraminidase (HN) and precursor fusion proteins (F0) showed them to have only a
      single amino acid difference: those with an ICPI value <0.7 had proline at amino
      acid position 453 of the F0 protein, and those with an ICPI value >0.7 contained
      a serine. The virus with an ICPI of 0.025 was further passaged, and the ICPI of
      non-cloned virus increased to 0.76/0.79, which was then reduced to 0.49 on
      cloning. The proline at residue 453 was retained, but there were two nucleotide
      changes in the virus of ICPI 0.49, T --> C at position 1769 in the untranslated
      region of the fusion gene and G --> A at position 437 of the HN gene, resulting
      in the amino acid change G --> R at position 116 in the HN protein.

PMID- 17514490
TI  - Rapid, simple and effective technical procedure for the regeneration of IgG and
      HSA affinity columns for proteomic analysis.
AB  - In plasma and serum, the presence of high-abundance proteins can overwhelm the
      signals of low-abundance proteins, which then become undetectable either by two
      dimensional gels or chromatographic techniques. Therefore, depletion of abundant
      proteins is a prerequisite to detect low-abundance components. Furthermore, the
      regeneration of pre-purification tools could be money-saving. We applied an
      affinity chromatography kit to remove albumin and the immunoglobulin chains from
      plasma and propose a simple and effective technical procedure for the
      regeneration of these affinity columns.

PMID- 17514491
TI  - Arabino-galactan proteins from Pistacia lentiscus var. chia: isolation,
      characterization and biological function.
AB  - Arabino-Galactan Proteins (AGPs) were isolated from Chios mastic gum (CMG) by
      using a buffer containing 0.1 M NaCl, 20 mM Tris-HCl, pH 7.5. Protein analytical
      methods, combined with specific procedures for carbohydrate characterization,
      indicated the presence of highly glycosylated protein backbone. In particular,
      staining by Yariv reagent of the electrophoretically separated molecules revealed
      the existence of arabinose and galactose and such a modification is
      characteristic for AGPs. After experiments involving extensive dialysis of the
      isolated extracts against water and atomic absorption, there was evidence of the
      existence of zinc ions that are probably covalently bound to the AGPs. By using
      anion-exchange chromatography, capillary electrophoresis, colorimetric methods
      and GC-MS, it was found that the extracts were separated into three major
      populations (A, B, and C), which were consistent with their respective negative
      charge content namely, uronic acid. The characterization of neutral sugars that
      was investigated with GC-MS showed the existence of arabinose and galactose in
      different amounts for each group. Experiments concerning the inhibition of growth
      of Helicobacter pylori in the presence of AGPs, as is shown for other CMG
      constituents, showed that the extracts of at least 1.4 g CMG affected the
      viability of the bacterium. There is no evidence as to whether the AGPs provoke
      abnormal morphologies of H. pylori, as is reported for the total CMG, or for O
      glycans that possess terminal alpha1, 4-linked N-acetylglucosamine and are
      expressed in the human gastric mucosa; this has to be further investigated.

PMID- 17514492
TI  - Sequence elements essential for the rapid turnover of Crithidia fasciculata
      ornithine decarboxylase.
AB  - Ornithine decarboxylase (ODC) has a very fast turnover in mammalian cells, but is
      a stable enzyme in T. brucei and other trypanosmatid parasites like Leishmania
      donovani. However, Crithidia fasciculata, which is a phylogenetically closely
      related trypanosomatid to L. donovani, has an ODC with a rapid turnover.
      Interestingly, C. fasciculata ODC, but not L. donovani ODC, is rapidly degraded
      also in mammalian systems. In order to obtain information on what sequences are
      important for the rapid degradation of C. fasciculata ODC, we produced a variety
      of C. fasciculata/L. donovani ODC hybrid proteins and characterized their
      turnover using two different mammalian expression systems. The results obtained
      indicate that C. fasciculata ODC contains several sequence elements essential for
      the rapid turnover of the protein and that these regions are mainly located in
      the central part of the enzyme.

PMID- 17514493
TI  - Using pseudo amino acid composition to predict protein subnuclear location with
      improved hybrid approach.
AB  - The subnuclear localization of nuclear protein is very important for in-depth
      understanding of the construction and function of the nucleus. Based on the amino
      acid and pseudo amino acid composition (PseAA) as originally introduced by K. C.
      Chou can incorporate much more information of a protein sequence than the
      classical amino acid composition so as to significantly enhance the power of
      using a discrete model to predict various attributes of a protein, an algorithm
      of increment of diversity combined with the improved quadratic discriminant
      analysis is proposed to predict the protein subnuclear location. The overall
      predictive success rates and correlation coefficient are 75.4% and 0.629 for 504
      single localization proteins in jackknife test, and 80.4% for an independent set
      of 92 multi-localization proteins, respectively. For 406 single localization
      nuclear proteins with < or =25% sequence identity, the results of jackknife test
      show that the overall accuracy of prediction is 77.1%.

PMID- 17514494
TI  - Production of gamma-aminobutyric acid by Streptococcus salivarius subsp.
      thermophilus Y2 under submerged fermentation.
AB  - Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the
      central nervous system, has several well-known physiological functions and has
      been applied to the production of many drugs and functional foods. The technology
      of GABA production via submerged fermentation by Streptococcus salivarius subsp.
      thermophilus Y2 was investigated in this paper. It indicated that the GABA
      production was related to the biochemical characteristics of glutamate
      decarboxylase (GAD) of S. salivarius subsp. thermophilus Y2. After 24 h of
      fermentation at 37 degrees C, which is the suitable culture conditions for GAD
      production, then the culture condition were adjusted to the optimal temperature
      (40 degrees C) and pH (4.5) for the GAD reaction activity in biotransformation of
      cells and pyridoxal 5'-phosphate (0.02 mmol/l) were added to the broth at the 48
      h, the GABA production was increased up to 1.76-fold, reaching 7984.75 +/- 293.33
      mg/l. The strain shows great potential use as a starter for GABA-containing
      yoghurt, cheese and other functional fermented food productions.

PMID- 17514495
TI  - Strategies for comprehensive analysis of amino acid biomarkers of oxidative
      stress.
AB  - Despite the wide interest in using modified amino acids as putative biomarkers of
      oxidative stress, many issues remain as to their overall reliability for early
      detection and diagnosis of diseases. In contrast to conventional single biomarker
      studies, comprehensive analysis of biomarkers offers an unbiased strategy for
      global assessment of modified amino acid metabolism due to reactive oxygen and
      nitrogen species. This review examines recent analytical techniques amenable for
      analysis of modified amino acids in biological samples reported during 2003-2007.
      Particular attention is devoted to the need for validated methods applicable to
      high-throughput analysis of multiple amino acid biomarkers, as well as
      consideration of sample pretreatment protocols on artifact formation for improved
      clinical relevance.

PMID- 17514496
TI  - Polyamines: metabolism to systems biology and beyond.
AB  - Polyamines and the metabolic and physiopathological processes in which they are
      involved represent an active field of research that has been continuously growing
      since the seventies. In the last years, the trends in the focused areas of
      interest within this field since the 1970s have been confirmed. The impact of "
      omics" in polyamine research remains too low in comparison with its deep impact
      on other biological research areas. These high-throughput approaches, along with
      systems biology and, in general, more systemic and holistic approaches should
      contribute to a renewal of this research area in the near future.

PMID- 17514497
TI  - Absorption, tissue distribution, metabolism and elimination of taurine given
      orally to rats.
AB  - Three biodisposition studies with taurine were performed in male and female adult
      rats at dosages of 30 and 300 mg/kg. A single oral dose of (14)C-taurine was
      rapidly absorbed, distributed to tissues and excreted unchanged in urine.
      Elimination of radioactivity from intracellular pools was slow. Pre-treatment of
      animals for 14 days with unlabelled taurine did not significantly affect the fate
      of (14)C-taurine. At the higher dose there was more extensive excretion combined
      with a lower percentage of the dose in the carcass, indicating the possibility of
      saturation of the tubular reabsorption mechanism for taurine. Daily
      administration of unlabelled taurine for 14 days did not result in an increase in
      total taurine in the brain. The data indicate that exogenous taurine rapidly
      equilibrates with endogenous body pools and that any excess is rapidly eliminated
      by the kidneys.

PMID- 17514498
TI  - Parametric analysis of metabolic fluxes of alpha-amylase and protease-producing
      Bacillus subtilis.
AB  - Parametric analysis was applied for a metabolic flux model for the fed-batch
      culture of Bacillus subtilis producing recombinant alpha-amylase and protease.
      The metabolic flux model was formulated as a linear programming problem
      consisting of 49 reactions (decision variables) and 50 metabolites (equality
      constraints). This study was aimed to determine the response of the metabolic
      fluxes and objective function value of minimizing the difference between ATP
      consumption and ATP production (ATP balance). With regard to intracellular
      metabolite accumulation, the objective function value was least sensitive to
      variation in succinate and most sensitive to variation in malate. Amongst the
      variations in the accumulation rates of extracellular metabolites, the objective
      function value was least sensitive to variation in glutamate and most sensitive
      to variation in starch hydrolysis and triglyceride synthesis. A 10% variation in
      metabolite accumulation rates caused a maximum of 13.8% variation (standard error
      = 3.8%) in the objective function value.

PMID- 17514499
TI  - Response of influenza vaccines against heterovariant influenza virus strains in
      adults with chronic diseases.
AB  - The ability of influenza vaccination to provide cross-protection against
      heterovariant influenza strains was evaluated in a double-blind, randomized,
      trial in north-east Italy during the winter of 2005-2006. Of 238 adult subjects
      with underlying chronic diseases, 120 received MF59-adjuvanted subunit vaccine
      (Sub/MF59) and 118 received a conventional subunit vaccine (Subunit).
      Immunogenicity was measured for A/H3N2 and B influenza strains against both the
      homologous vaccine strains (A/New York/55/2004 and B/Jiangsu/10/2003), and the
      heterovariant strains recommended for the 2006-2007 season (A/Wisconsin/67/2005
      and B/Malaysia/2506/2004). Although both vaccines conferred serological
      protection against the homologous vaccine strains and the 2006-2007 heterovariant
      A/H3N2 strain for a majority of subjects, the antibody response was highest in
      the Sub/MF59 vaccine group. For example, MF59-adjuvanted vaccination conferred
      significantly greater (P = 0.002) protection against the heterovariant A/H3N2
      strain than the conventional subunit vaccine (79.2% vs. 61.0% of subjects,
      respectively). In conclusion, these results demonstrate that protection provided
      by influenza vaccination in adults affected by chronic diseases is lower against
      heterovariant strains than for homologous strains. However, addition of MF59
      adjuvant to a subunit vaccine enhances immunogenicity against the A/H3N2
      heterovariant strain, conferring broader protection than a conventional subunit
      vaccine in this population, who are at higher risk of influenza-related
      complications.

PMID- 17514500
TI  - Two patients with complete defects in interferon gamma receptor-dependent
      signaling.
AB  - Unusual susceptibility to mycobacterial infections can be caused by deleterious
      mutations in genes that encode the interferon-gamma receptor 1 chain. Such
      mutations hamper the activation of macrophages by a type 1 immune response and
      result in enhanced survival of intracellular pathogens. We here report two
      patients with unusual mycobacterial infections, both diagnosed with homozygous
      deleterious interferon-gamma receptor 1 gene mutations. Patient 1 became ill
      after Bacillus Calmette-Guerin vaccination at the age of 9 months and died at the
      age of 18 months. She carried a homozygous C71Y mutation in the extracellular
      part of the mature interferon-gamma receptor 1 protein, resulting in the lack of
      detectable protein expression and absence of interferon-gamma dependent
      signaling. Patient 2 became ill at the age of 3 years, is still alive at 19 years
      of age, and has suffered from five successive infection episodes with atypical
      mycobacteria. A homozygous splice-site mutation in intron 3 was identified,
      resulting in the deletion of exon 3 at the mRNA level and consequently a
      truncated interferon-gamma receptor 1 protein with absence of the transmembrane
      domain. Protein expression and interferon-gamma dependent signaling were not
      detectable.

PMID- 17514501
TI  - Diagnostic relevance and clinical significance of the new enhanced performance M2
      (MIT3) ELISA for the detection of IgA and IgG antimitochondrial antibodies in
      primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Antimitochondrial antibodies (AMAs) are the serological hallmark
      of primary biliary cirrhosis (PBC). We evaluated the sensitivity and specificity
      of a new M2 enhanced performance enzyme-linked immunosorbent assay (ELISA) (MIT3)
      for the detection of IgG- and IgA-specific isotypes of AMA in PBC patients
      including a number of PBC patients negative for AMA by indirect
      immunofluorescence (IIF) as well as in patients with diverse, non-PBC disorders.
      We also investigated the clinical significance of IgG and IgA AMA in PBC.
      METHODS: One hundred and three Greek PBC patients including 27 with AMA IIF
      negative at the time of the investigation, 29 with autoimmune hepatitis-1 (AIH
      1), 12 with primary sclerosing cholangitis (PSC), 26 with hepatitis C virus
      (HCV), 15 with hepatitis B virus (HBV), and 29 healthy were investigated for AMA
      (IgG and IgA) using the MIT3-based ELISAs (INOVA Diagnostics, San Diego, CA). The
      samples were also tested by conventional anti-M2 ELISA (INOVA Diagnostics, Inc.).
      RESULTS: The IgG MIT3-based ELISA significantly increased AMA detection in the
      cohort of PBC patients, over 26% of whom were AMA IIF-negative, from 63.1% by the
      conventional anti-M2, and 73.7% by IIF to 79.6% by MIT3-based ELISA (p<0.001).
      IgA AMAs were detected in 47.6% patients. Overall, IgG/IgA AMAs were detected in
      84/103 (81.6%). IgG MIT3-based ELISA detected 12/27 IIF AMA-negative samples
      (44.4%), while IgG/IgA MIT3-based ELISAs detected 13/27 IIF AMA-negative patients
      (48.1%). The specificities of MIT3-based ELISAs (IgG and IgA) were 82.8% and
      89.7%, respectively, in AIH-1, 100% and 93.3%, respectively, in HBV, 100% in PSC,
      and 96% and 93.3%, respectively, in HCV. Patients positive for IgG AMA had
      significantly more severe disease as shown by worse histology and elevated
      biochemical markers; IgG and IgA AMA titers were associated positively with the
      Mayo risk score but none of the isotypes were able to predict disease outcome.
      CONCLUSIONS: The new IgG and IgA MIT3-based ELISAs seem to have higher
      specificity and sensitivity for AMA detection than IIF and the conventional anti
      M2. Interestingly, these assays were able to unmask AMA presence in almost half
      of the AMA-negative samples by IIF. These findings may suggest the use of MIT3
      based ELISAs as first-line investigation for AMA detection, particularly, when
      the laboratories are unfamiliar with the use and interpretation of the IIF
      patterns of AMA. The presence of IgG AMA seems to characterize PBC patients with
      more severe disease, but both IgG and IgA isotypes of AMAs were not predictive
      markers of disease outcome.

PMID- 17514502
TI  - FACT: a Dutch version of ACT.
AB  - Assertive Community Treatment (ACT) is a well-defined service delivery model for
      the care and treatment of the most severely mentally ill in the community. We
      have opted for a Dutch version named 'Function' ACT or FACT. In a FACT team, ACT
      is one of the functions that the team can perform. For more stable long-term
      patients FACT provides coordinated multidisciplinary treatment and care by
      individual case management. Unstable patients at risk of relapse are followed
      with assertive outreach care by the same team, working with a shared caseload for
      this subgroup. This article describes the service model and everyday practice in
      FACT.

PMID- 17514503
TI  - ACT and recovery: integrating evidence-based practice and recovery orientation on
      assertive community treatment teams.
AB  - We examine whether Assertive Community Treatment (ACT), a widely implemented and
      rigorously studied practice, can successfully incorporate a recovery-oriented
      approach while continuing to retain program fidelity. We briefly review the
      effectiveness of ACT as an evidence-based practice, with a focus on adaptations
      to changing populations and contexts. We explore philosophical similarities and
      differences between ACT and recovery and examine how fidelity standards, a widely
      used indicator of how ACT teams operate, support or interfere with the adoption
      of a recovery-oriented practice. Finally, we provide recommendations on how best
      to incorporate a recovery orientation into existing ACT teams.

PMID- 17514504
TI  - Measuring illness management outcomes: a psychometric study of clinician and
      consumer rating scales for illness self management and recovery.
AB  - Psychometric properties of the Illness Management and Recovery (IMR) Scales
      (consumer and clinician versions), new 15-item instruments measuring illness self
      management and pursuit of recovery goals, were evaluated in consumers with severe
      mental illness. Both versions had moderate internal consistency and high 2-week
      test-retest reliability. In addition, the consumer version was correlated with
      self-ratings of recovery and symptoms, and the clinician version was correlated
      with clinician ratings of community functioning, indicating convergent validity.
      The results suggest the IMR Scales have adequate psychometric properties and may
      be useful in treatment planning and assessing recovery in individuals with severe
      mental illness.

PMID- 17514505
TI  - What contribution can ordinary people make to national mental health policies?
AB  - Recent development practice has begun to demonstrate the possibilities of local
      communities engaging in local mental health policy and has been the subject of
      much research. The challenge now is to apply this grassroots learning to the
      development of national mental health policy and thus address the gap between the
      top-down and bottom-up styles of policy-making. This report describes the
      progress and achievements of grassroots organisations and people with mental
      health problems in Romania in developing policies to promote community-based
      mental health services at a national level.

PMID- 17514506
TI  - Characteristics of calls to the Israeli hotline during the Intifada.
AB  - The present study examined the help-seeking characteristics of callers to the ten
      Israeli hotline centers during the Intifada - the Palestinian uprising in the
      Israeli administered territories. The research method combined quantitative and
      qualitative analyses of the volunteers' written reports. The quantitative
      analysis was conducted on a sample of 21,315 structured forms, and the
      qualitative content analysis was carried out on a sample of 498 verbal
      descriptions of calls. The quantitative analysis revealed a U-shaped curve
      illustrating the frequency of Intifada-related calls in relation to the time of
      the study. The qualitative analysis showed that the main complaints of the
      callers were focused on direct and masked manifestations of anxiety and feelings
      of helplessness. The implications of the findings are discussed in terms of
      understanding the unique psychological response to a new kind of stress, as seen
      from the perspective of calls to a hotline.

PMID- 17514507
TI  - Very long chain acyl-CoA dehydrogenase deficiency in a pair of mildly affected
      monozygotic twin sister in their late fifties.
AB  - Very long-chain acyl-CoA dehydrogenase (VLCAD) catalyses the initial step of
      mitochondrial beta-oxidation of long-chain fatty acids with a chain length of 14
      to 20 carbons. Deficiency of VLCAD activity has been associated with a range of
      phenotypes, including a severe lethal form presenting in the infantile period and
      a milder variant with onset in childhood. Varying rates of residual enzyme
      activity partly explain the heterogeneity in presentations. Here we report the
      course of disease in a pair of monozygotic twin sisters who were diagnosed in
      their late forties during an evaluation for rhabdomyolysis and fatigue.
      Interestingly, the patients' complaints were most severe during puberty and
      declined significantly after the menopause. The basis for this observation is
      uncertain, but may be related to hormonally-mediated changes in lipid metabolism
      that may occur at these times. As metabolic decompensation can be associated with
      significant morbidity, timely diagnosis of VLCAD deficiency is important. The
      introduction of appropriate dietary measures (i.e. avoidance of fasting, long
      chain fat restriction and supplementation with medium-chain triglycerides)
      greatly reduces the likelihood of complications.

PMID- 17514508
TI  - Outcome of pectoralis major myomammary flap for post-mastectomy breast
      reconstruction: extended experience.
AB  - BACKGROUND: In the past decade there has been an enormously expanding interest
      among rural Egyptian patients, relatives, and treating oncologists in post
      mastectomy reconstruction as an integral part of patient care. We introduced our
      technique of pectoralis major myomammary cutaneous flap for single-stage
      reconstruction of large breasts, nipple, and areola. METHODS: The new technique
      is based on performing modified radical mastectomy in the classic manner, and
      then using a pectoralis major myocutaneous pedicled flap from the other side in
      breast reconstruction. The flap is based on the pectoral branch of the
      thoracoacromial artery, and a sector from the medial part of the healthy breast
      with its overlying skin and a part of the nipple-areola complex is included with
      the flap. This technique was used in our center in one 118 patients, with very
      promising results. RESULTS: Major flap necrosis was not observed in patients
      treated with this technique, and there were no local recurrences observed during
      the follow-up period. Excellent cosmetic results were achieved in 49 of the 118
      (41.5%) cases. CONCLUSION: We recommend this new technique as a single-stage,
      simple solution for reconstruction of large breasts after mastectomy.

PMID- 17514510
TI  - A kinetic core model of the glucose-stimulated insulin secretion network of
      pancreatic beta cells.
AB  - The construction and characterization of a core kinetic model of the glucose
      stimulated insulin secretion system (GSIS) in pancreatic beta cells is described.
      The model consists of 44 enzymatic reactions, 59 metabolic state variables, and
      272 parameters. It integrates five subsystems: glycolysis, the TCA cycle, the
      respiratory chain, NADH shuttles, and the pyruvate cycle. It also takes into
      account compartmentalization of the reactions in the cytoplasm and mitochondrial
      matrix. The model shows expected behavior in its outputs, including the response
      of ATP production to starting glucose concentration and the induction of
      oscillations of metabolite concentrations in the glycolytic pathway and in ATP
      and ADP concentrations. Identification of choke points and parameter sensitivity
      analysis indicate that the glycolytic pathway, and to a lesser extent the TCA
      cycle, are critical to the proper behavior of the system, while parameters in
      other components such as the respiratory chain are less critical. Notably,
      however, sensitivity analysis identifies the first reactions of nonglycolytic
      pathways as being important for the behavior of the system. The model is robust
      to deletion of malic enzyme activity, which is absent in mouse pancreatic beta
      cells. The model represents a step toward the construction of a model with
      species-specific parameters that can be used to understand mouse models of
      diabetes and the relationship of these mouse models to the human disease state.

PMID- 17514509
TI  - Comparative genetic analysis: the utility of mouse genetic systems for studying
      human monogenic disease.
AB  - One of the long-term goals of mutagenesis programs in the mouse has been to
      generate mutant lines to facilitate the functional study of every mammalian gene.
      With a combination of complementary genetic approaches and advances in
      technology, this aim is slowly becoming a reality. One of the most important
      features of this strategy is the ability to identify and compare a number of
      mutations in the same gene, an allelic series. With the advent of gene-driven
      screening of mutant archives, the search for a specific series of interest is now
      a practical option. This review focuses on the analysis of multiple mutations
      from chemical mutagenesis projects in a wide variety of genes and the valuable
      functional information that has been obtained from these studies. Although gene
      knockouts and transgenics will continue to be an important resource to ascertain
      gene function, with a significant proportion of human diseases caused by point
      mutations, identifying an allelic series is becoming an equally efficient route
      to generating clinically relevant and functionally important mouse models.

PMID- 17514511
TI  - Chromosomal instability in human mesenchymal stem cells immortalized with human
      papilloma virus E6, E7, and hTERT genes.
AB  - Human mesenchymal stem cells (hMSCs) are expected to be an enormous potential
      source for future cell therapy, because of their self-renewing divisions and also
      because of their multiple-lineage differentiation. The finite lifespan of these
      cells, however, is a hurdle for clinical application. Recently, several hMSC
      lines have been established by immortalized human telomerase reverse
      transcriptase gene (hTERT) alone or with hTERT in combination with human
      papillomavirus type 16 E6/E7 genes (E6/E7) and human proto-oncogene, Bmi-1, but
      have not so much been characterized their karyotypic stability in detail during
      extended lifespan under in vitro conditions. In this report, the cells
      immortalized with the hTERT gene alone exhibited little change in karyotype,
      whereas the cells immortalized with E6/E7 plus hTERT genes or Bmi-1, E6 plus
      hTERT genes were unstable regarding chromosome numbers, which altered markedly
      during prolonged culture. Interestingly, one unique chromosomal alteration was
      the preferential loss of chromosome 13 in three cell lines, observed by
      fluorescence in situ hybridization (FISH) and comparative-genomic hybridization
      (CGH) analysis. The four cell lines all maintained the ability to differentiate
      into both osteogenic and adipogenic lineages, and two cell lines underwent
      neuroblastic differentiation. Thus, our results were able to provide a step
      forward toward fulfilling the need for a sufficient number of cells for new
      therapeutic applications, and substantiate that these cell lines are a useful
      model for understanding the mechanisms of chromosomal instability and
      differentiation of hMSCs.

PMID- 17514512
TI  - A novel tissue array technique for high-throughput tissue microarray analysis --
      microarray groups.
AB  - Tissue microarrays are ordered arrays of hundreds to thousands of tissue cores in
      a single paraffin block. We invented a novel method to make a high-throughput
      microarray group. Conventional smaller tissue microarrays were made first and
      then sectioned. Separate paraffin films were arrayed orderly onto a regular-sized
      glass slide to form a larger microarray group. Sections were not floated in a
      water bath but, rather, were cut singly using conventional microtome, arrayed
      orderly onto the glass slide with forceps instead of using a tape-based tissue
      transfer system, and then unfolded with warm water (46 degrees C) using a
      micropipette. This not only lowers the difficulty in sectioning but the overall
      tissue disks can be included in the same section. A microarray group of 2,534
      small disks (theoretically, 2,560 disks can be made; 26 fell off during the
      procedure), the most up to now, was successfully made and may be used in
      immunohistochemistry, mRNA in situ hybridization, and flourescent in situ
      hybridization.

PMID- 17514513
TI  - Use of local anesthesia in restorative treatment for adults in Finland.
AB  - OBJECTIVE: In this survey we investigated the frequency of use of local
      anesthesia (LA) in restorative treatment for vital teeth in adults in Finland.
      MATERIAL AND METHODS: A postal questionnaire was mailed to 592 dentists selected
      by systematic sampling from the membership list of the Finnish Dental
      Association; 57% responded. The questionnaire inquired "How often do you use
      local anesthesia when restoring vital teeth in adults?" for three types of
      primary restorations: class III for incisors, class II for premolars or molars,
      and class V on gingival margin for premolars or molars. Statistical evaluation
      included chi-square and logistic regression modeling. RESULTS: For restorative
      treatment of class III primary restoration for incisors, 21% of the dentists used
      LA always or almost always, 47% fairly often, 30% occasionally, and 2% rarely or
      never. For class II restoration for premolars or molars, 25% of dentists used LA
      always or almost always, 58% used LA fairly often, 16% occasionally, and 1%
      rarely or never. Controlling for gender and time elapsed since graduation, public
      dentists were more likely to use LA always or almost always for Class II (OR=2.0)
      and Class III (OR=1.8) restorations. No such difference appeared for Class V
      restorations. CONCLUSION: The majority of dentists have accepted LA as part of
      their everyday practice, with more widespread use among public dentists. Still,
      to prevent future dental fear among patients, dentists should emphasize pain-free
      treatment.

PMID- 17514514
TI  - Familial occurrence of signs of temporomandibular disorders in headache children
      and their mothers.
AB  - OBJECTIVE: Earlier studies have provided evidence of genetic inheritance of
      headache, especially migraine, but no familial occurrence has been found
      regarding temporomandibular disorders (TMD). In adults, headache and TMD have
      been found to be associated with each other, but studies on children are few. The
      aim of the present study was to test the hypothesis that there is no association
      between signs of TMD in 13-year-old headache children and their mothers. MATERIAL
      AND METHODS: The study population was a nested case-control study of the
      population-based Finnish Family Competence Study originally consisting of over
      1000 families. A structured questionnaire was sent to the families of 6-year-old
      children. A clinical examination was performed in 96 children with headache and
      96 pairwise controls. At the age of 13 years, 75 of these same 96 children with
      headache and 79 of 96 headache-free controls participated in pediatric and
      stomatognathic examinations. Moreover, the mothers (n=154) filled in a structured
      headache questionnaire and participated in the stomatognathic examination.
      RESULTS: No association between mother's and child's TMD signs was found. There
      was a significant association between signs of TMD and both migraine and tension
      type headache in children. In mothers, the association was significant only
      between migraine and TMD signs. CONCLUSIONS: Familial occurrence of signs of TMD
      cannot be found in headache children and their mothers.

PMID- 17514515
TI  - Reinforcing effect of glass-fiber-reinforced composite on flexural strength at
      the proportional limit of denture base resin.
AB  - OBJECTIVE: To evaluate the reinforcing effect of fiber-reinforced composite (FRC)
      on flexural strengths at the proportional limit (FS-PL) of a denture base resin.
      MATERIAL AND METHODS: Bar-shaped acrylic resin specimens and maxillary acrylic
      resin complete denture specimens were fabricated. The FS-PL of the reinforced bar
      shaped specimens was tested. Novel FRC, FibreKor, Remanium, Palatal Bar Wire, and
      Clasp-Wire were used as reinforcing materials. Likewise, the compressive strength
      at the proportional limit (CS-PL) of the reinforced maxillary denture specimens
      was tested. RESULTS: The FS-PL of the bar-shaped specimens reinforced with the
      FRCs was significantly higher than that of the unreinforced specimens. The FS-PL
      of the bar-shaped specimens reinforced with the 1.0-mm-thick FRC was similar to
      the FS-PL of specimens reinforced with Remanium or Palatal Bar Wire. The FS-PL of
      specimens reinforced with the 1.5-mm-thick FRC was significantly higher than with
      the metal-reinforcing materials. The reinforcing efficiency of the 1.0-mm-thick
      FRC was 1.78-1.79 and of the 1.5-mm-thick FRC 3.14-3.27. The reinforcing effect
      of the FRC on the CS-PL of the maxillary denture specimen was similar to the
      effect on the FS-PL of the bar-shaped specimens. The reinforcing efficiency was
      1.40 for the 1.0-mm-thick FRC and 1.67 for the 1.5-mm-thick FRC. CONCLUSION: The
      unidirectional glass-fiber-reinforced composite had a reinforcing effect on the
      flexural strength at the proportional limit of the denture base resin.

PMID- 17514516
TI  - Photographic assessment of fluorosis in children from naturally fluoridated
      Kungsbacka and non-fluoridated Halmstad, Sweden.
AB  - OBJECTIVES: To assess levels of fluorosis and fluorosis of esthetic concern in
      children from a naturally fluoridated and a non-fluoridated area of Sweden, and
      to determine the relative contributions of fluoridated water, parental
      educational level, and infant oral health-related behaviors. METHODS: A parental
      questionnaire collected information concerning child F-supplement and F
      dentifrice usage histories, and socio-economic status. Photographic examination
      of 1336 subjects (F=791; N-F=545) was undertaken. Fluorosis was assessed (blind
      to F-exposure) in a random sample (n=250) of 35 mm slides by four dental and two
      lay "jurors" (with 10% random repeat-viewing for inter-observer and intra
      observer agreement). Four outcomes were assessed on each slide: fluorosis at any
      level, fluorosis of esthetic concern, acceptability of appearance, and treatment
      needs. Ordinal logistic regression models were used to determine significant
      determinants. RESULTS: For presence of fluorosis of esthetic concern, majority
      jury agreements (>3 of 6) were seen in only 2.3% (N-F) and 13.4% (F) pupils
      (p<0.001), albeit jurors unanimously scored only 13 F and 2 N-F exposed children
      as having esthetically unacceptable fluorosed teeth (p<0.001). The over-riding
      significant factor in terms of fluorosis of esthetic concern was exposure to
      water fluoridation in infancy in both unadjusted and adjusted models.
      CONCLUSIONS: The important factor in relation to fluorosis of esthetic concern
      was explained by exposure to fluoridated water in infancy, and was not explained
      by age, sex, level of parental education or early childhood oral health
      behaviors. However, prevalence of this condition was relatively low. These
      findings should inform policies on appropriate total fluoride exposure levels
      during infancy.

PMID- 17514517
TI  - Langerin-expressing and CD83-expressing cells in oral lichen planus lesions.
AB  - OBJECTIVE: Dendritic Langerhans cells (LCs) have been attributed a role in the
      pathogenesis of lichen planus as autoantigen-presenting cells initiating
      expansion of autoreactive T cells. Langerin and CD83, which are cell molecules
      expressed on LCs, are associated with antigen presentation. The present study
      examined expression of Langerin and CD83 molecules on LCs in patients with oral
      lichen planus (OLP). MATERIAL AND METHODS: Biopsies were obtained from seven
      patients with OLP. Oral mucosa from seven healthy subjects served as controls.
      Monoclonal antibodies (mAbs) were used in standard immunohistochemical procedures
      to visualize CD1a-, Langerin-, and CD83-molecule-expressing cells. RESULTS: CD1a+
      and Langerin+ cells were found in significantly higher frequencies in OLP
      epithelium compared with healthy oral epithelium (p<0.01 and p<0.05,
      respectively); however, the frequency of CD83+ cells did not differ (p>0.05). The
      connective tissue in OLP lesions showed significantly higher frequencies of
      CD1a+, Langerin+, and CD83+ cells compared with healthy connective tissue
      (p<0.01, p<0.01, and p<0.05). CD1a+ and Langerin+ cells in OLP and healthy
      epithelium had a dendritic morphology. CONCLUSIONS: The study shows increased
      numbers of CD1a- and Langerin-expressing LCs in OLP compared with healthy
      controls. In the connective tissue, CD83+ cells with dendritic morphology were
      localized to regions of lymphocyte clusters. The presence of CD83+ dendritic
      cells in areas of lymphocyte clusters in the connective tissue of OLP lesions
      indicates the possibility of ongoing autoantigen presentation.

PMID- 17514518
TI  - Stimulated salivary flow rate and buffer effect in schoolchildren from Greenland
      and Sweden: a comparative study.
AB  - OBJECTIVE: To compare food habits and stimulated salivary flow rate and buffer
      effect between schoolchildren from Greenland and Sweden and to evaluate whether
      the change in lifestyle concerning eating habits in Sweden during recent decades
      has resulted in any obvious alteration in these salivary properties. MATERIAL AND
      METHODS: Fifty healthy schoolchildren from Greenland were included and compared
      with 50 age-matched and gender-matched Swedish children. Whole saliva stimulated
      by chewing was collected, and prior to sampling each participant filled in a
      simple questionnaire regarding their food habits. RESULTS: Salivary flow rate and
      buffer effect were significantly (p<0.001) higher for the Greenlandic children.
      The difference in flow rate was on average 0.71 ml/min. Milk, fish/meat and
      fruit/vegetables were more frequently consumed by the Swedish children, while
      snacks, soft drinks and sweets had a higher consumption frequency on Greenland.
      No obvious correlation could be found between consumption frequency of the tested
      food products and flow rate or buffer effect of saliva. Twenty-nine Swedish
      children were within the age range+/-6 months of an age with earlier documented
      values of stimulated salivary flow rate. Twenty-six of these 29 Swedish children
      were within the 25-75 percentile range of the old values, while 22 of their
      Greenlandic "twins" were in or above percentile 75. CONCLUSIONS: Obvious
      differences in salivary flow rate and buffer effect between schoolchildren from
      Greenland and Sweden illustrated the importance of being cautious when exchanging
      reference data between different cultures/ethnic groups.

PMID- 17514519
TI  - Bacterial reduction by extensive versus conservative root canal instrumentation
      in vitro.
AB  - OBJECTIVE: This study aimed to test the hypothesis that aggressive dentin removal
      through greater-tapered instrumentation reduces the intracanal bacteria more
      effectively than conservative dimension instrumentation. MATERIAL AND METHODS:
      Twenty extracted human lower premolar teeth were used. After extirpation of the
      pulps, the teeth were autoclaved and immersed in a broth inoculated with
      Enterococcus faecalis and incubated for 7 days to allow infection of the dentinal
      tubules. The teeth were divided into 2 experimental groups, each comprising 10
      teeth. The teeth were instrumented either with ProTaper or with Hero Shaper
      nickel-titanium rotary instrumentation techniques. It was calculated that
      ProTaper theoretically has the potential to remove at least twice the dentin
      volume compared with Hero Shaper. The apical preparation was standardized to file
      size 30. Saline solution was used for irrigation. Bacteriological samples were
      taken before and after instrumentation and plated onto tryptic soy agar, and the
      reduction in numbers was calculated. RESULTS: Both instrumentation techniques
      significantly reduced the number of bacteria in the root canal (p<0.05).
      Reduction in absolute bacterial numbers was up to 98%. There was no statistically
      significant difference between the two techniques. CONCLUSIONS: Preparation with
      an instrumentation technique removing substantial amounts of dentin did not
      reduce the intracanal bacteria more effectively than a more conservative
      instrumentation technique.

PMID- 17514520
TI  - Electron-beam irradiation of experimental denture base polymers.
AB  - OBJECTIVE: Since the properties of polymers can be influenced using electron-beam
      irradiation, the aim of this study was to investigate whether electron-beam post
      curing can improve the mechanical properties of experimental denture base
      polymers. MATERIAL AND METHODS: Rectangular specimens of different experimental
      polymeric blends were electron-beam irradiated (post-cured) with 25 kGy and 200
      kGy using an electron accelerator of 4.5 MeV. Fracture toughness, work of
      fracture, Vickers hardness and colour changes were measured and compared in non
      irradiated specimens. RESULTS: The mechanical properties of all the investigated
      polymers seemed to benefit from low-energy electron-beam irradiation (25 kGy).
      Using an energy dose of 200 kGy, all blends showed deteriorated mechanical
      properties resulting from chain breakage. Nevertheless, all investigated polymers
      had undesirable colour changes after electron-beam irradiation. CONCLUSIONS:
      Mechanical properties of experimental polymethyl-methacrylate could be changed
      using electron-beam irradiation. Because of discolorations caused by the
      irradiation levels investigated, these levels cannot be recommended for practical
      applications.

PMID- 17514521
TI  - The district nurse's perceptions of elderly patients' oral health: a qualitative
      interview study.
AB  - OBJECTIVE: The aim of this qualitative study based on interviews was to explore
      the perceptions that district nurses have of the oral health of elderly patients.
      MATERIAL AND METHODS: The criterion for inclusion was being a district nurse
      working in a primary health-care centre in the County of Stockholm. The
      respondents were asked open-ended questions about their perceptions of oral
      health and about the impact of oral problems on the general health and well-being
      of elderly patients. The analyses started at the first interview and proceeded in
      parallel until no further relevant information could be obtained. Analysis of the
      open-ended questions was inspired by grounded theory methodology and comprised
      four stages: native reading, open coding, axial coding, and selective coding.
      RESULTS: The one core category identified, namely indistinct professional duties
      of the district nurse, formed the central meaning of the district nurse's
      perceptions of oral health in elderly patients. This related to two other
      categories labelled 'insights into the district nurse's professional role' and
      'obstacles for the district nurse', with sub-categories. CONCLUSION: Although the
      district nurses in this study were aware of the impact of oral health in old age,
      their attitude was that this was a matter for dentistry.

PMID- 17514522
TI  - In vivo detection of non-cavitated caries lesions on occlusal surfaces by visual
      inspection and quantitative light-induced fluorescence.
AB  - OBJECTIVE: The aim of this clinical caries detection study was to compare the
      outcome of quantitative light-induced fluorescence (QLF) and meticulous visual
      inspection (VI) in detecting non-cavitated caries lesions on occlusal surfaces in
      young adolescents. It was hypothesized that the respective diagnostic
      performances of meticulous VI and QLF are similar. MATERIAL AND METHODS: The
      subjects were 34 fifteen-year-old students. Five-hundred-and-seventeen cleaned
      occlusal surfaces were air-dried and examined using VI. Fluorescence images were
      captured with QLF equipment and custom software was used to display, store and
      analyze the images. The area of the lesion (area; mm2), fluorescence loss
      (DeltaF;%) and DeltaQ (Area*DeltaF; mm2*%) were determined at a QLF threshold of 
      5%. The presence/absence of non-cavitated lesions was independently recorded with
      both methods. RESULTS: 78.8% of all untreated surfaces were classified as sound
      or as having a non-cavitated lesion with both methods uniformly (VI+QLF). On 7.1%
      of all surfaces a lesion was detected by VI only and on 14.1% by QLF only. All
      parameters (Area, DeltaF, DeltaQ) differed significantly between lesions
      registered with both methods (VI+QLF) and lesions recorded with QLF only.
      CONCLUSIONS: It was concluded that our hypothesis cannot be confirmed. The study
      shows that QLF detects (1) more non-cavitated occlusal lesions and (2) smaller
      lesions compared to VI. However, taking into consideration time-consuming image
      capturing and analysis, QLF is not really practical for use in the dental office.

PMID- 17514523
TI  - Androgen influence on cholesterogenic enzyme mRNA levels in the mouse meibomian
      gland.
AB  - PURPOSE: We tested our hypothesis that testosterone increases the meibomian gland
      gene expression of numerous enzymes in the cholesterol biosynthetic pathway.
      METHODS: Meibomian glands were obtained from castrated mice treated with vehicle
      or testosterone for 2 weeks. Tissues were processed for the analysis of selected
      mRNAs by real-time PCR. RESULTS: Our research demonstrates that testosterone
      stimulates a significant increase in the mRNA levels of mevalonate kinase,
      phosphomevalonate kinase, mevalonate pyrophosphate decarboxylase, isopentenyl
      pyrophosphate isomerase, geranylgeranyl pyrophosphate synthase, squalene
      epoxidase, lanosterol synthase, lanosterol demethylase, and Delta 7-sterol
      reductase. CONCLUSIONS: Our findings indicate that androgens may promote
      cholesterol biosynthesis in the meibomian gland.

PMID- 17514524
TI  - Fibrin glue versus vicryl sutures for primary conjunctival closure in pterygium
      surgery: long-term results.
AB  - PURPOSE: To compare the long-term results of conjunctival closure with fibrin
      adhesive or Vicryl sutures in pterygium surgery. METHODS: The study was performed
      in 81 patients (81 eyes) with primary nasal pterygium. Surgery in all patients
      consisted of the bare sclera technique combined with intraoperative
      administration of mitomycin C 0.02%. Patients were randomized to undergo
      conjunctival closure with a fibrin adhesive (Quixil) (n = 42) or Vicryl sutures
      (n = 39). Clinical assessment was performed on postoperative days 1, 3, 10, and
      21 and thereafter at 3, 6, and 12 months. All patients completed a questionnaire
      at each follow-up visit grading pain, discomfort, and satisfaction with the
      procedure. The groups were compared for operative time, ocular signs and
      symptoms, overall satisfaction, and recurrence rate. RESULTS: Average operative
      time was 16 min in the fibrin-glue group and 28 minutes in the Vicryl-suture
      group (p < 0.05). Significantly less pain and discomfort were noted in the
      subjects treated with glue than in controls (p < 0.05). Satisfaction was
      significantly higher in the study group (p < 0.04). There were no complications
      during follow-up period in the glue-treated patients; one patient in the suture
      group had a medically treatable corneal dellen. At the end of follow-up,
      recurrent pterygium developed in five (11.9%) eyes of the fibrin-glue group and
      in three (7.7%) eyes of the Vicryl-suture group (p < 0.05). CONCLUSIONS: The use
      of fibrin glue in pterygium surgery significantly reduces operative time and
      patient pain compared with suturing. However, it may be associated with a higher
      recurrence rate.

PMID- 17514525
TI  - Preoperative evaluation of cultured human corneal limbal epithelium on amniotic
      membrane by confocal microscopy.
AB  - PURPOSE: Although sheet transplantation with cultured corneal limbal epithelium
      has been widely performed as a strategy for ocular surface reconstruction, there
      has been no optimal method for evaluating the morphology of these sheets prior to
      transplantation. We propose the use of in vivo confocal microscopy as a novel
      method for the evaluation of limbal corneal epithelium cultured on amniotic
      membrane. METHODS: Human limbal epithelial sheets were grown on amniotic
      membranes by following a standard protocol and were stained with hematoxylin and
      eosin. Morphology was studied using in vivo confocal microscopy for cultured
      corneal epithelium on amniotic membrane, human intact amniotic membranes, and
      epithelium-denuded human amniotic membranes. RESULTS: Histologic examination
      showed a stratified corneal epithelium sheet by the fourth week of culture. The
      surface and basal layers of the cultured limbal epithelium and amniotic membrane
      were clearly distinguished by in vivo confocal microscopy. A monolayer of
      amniotic epithelial cells was observed on the intact amniotic membrane, but not
      on the epithelium-denuded human amniotic membrane. CONCLUSIONS: Our findings
      support the use of in vivo confocal microscopy as a valid technique for the
      preoperative evaluation of cultured corneal limbal epithelial cell sheets on
      amniotic membrane.

PMID- 17514526
TI  - Factors influencing central corneal thickness in a Turkish population.
AB  - PURPOSE: The aim of this study is to find out the central corneal thickness (CCT)
      values for a Turkish patient group and to investigate the possible influences of
      age, sex, IOP, refractive status, keratometry readings, systemic disorders
      (hypertension, diabetes mellitus, hyperlipidemia, heart disease and asthma) on
      CCT values. MATERIALS AND METHODS: Six hundred twenty five subjects (276 male
      (44%), 349 female (56%)) of ages 6 to 88 years were recruited. Subjects who had
      corneal diseases, purulent conjunctivitis or blepharitis were excluded.
      Refraction and keratometry readings were made by MRK-3100 premium auto
      ref/keratometer, IOP was measured by Reichert AT-555 auto noncontact
      pneumotonometer. RESULTS: Mean age was 44.1 +/- 16.6 years +/- SD for male
      subjects, 41.0 +/- 16.9 for females. Mean CCT +/- SD values for male was 552.2 +/
      35.9 microm, for female was 552.3 +/- 35.4 microm, respectively. There was no
      significant difference between right and left eye CCT values for both genders.
      Age and CCT was not correlated for the whole study group but there was a slight
      negative correlation in male subjects. IOP and CCT had moderately significant
      correlation for males and females. There was a slight significant correlation
      between Kh-Kv and CCT values for the whole group. In a multivariate regression
      model only Kv values seemed to affect CCT values. DISCUSSION: There are studies
      showing the variation of CCT values among different nations and ethnicities.
      There is no agreement about the relationship between age, IOP, Kh-Kv, spherical
      equivalence of refractive error, systemic disorders, menopause and CCT. In our
      study CCT was correlated with Kh-Kv and IOP in correlation analysis but in
      multivariate regression analysis only Kv appeared to influence corneal thickness.

PMID- 17514527
TI  - Calculations of corneal power after corneo-refractive surgery from keratometry
      and change of spectacle refraction: some considerations on the "clinical history
      method".
AB  - PURPOSE: To derive corneal power after kerato-refractive laser surgery (KRS) to
      be used for a subsequent intraocular lens (IOL) power calculation. MODEL: Based
      on the proportion of curvatures of the corneal front and back surface, the
      central thickness, and the ablation characteristics, we demonstrate a vergence
      based formalism to derive the equivalent and back vertex corneal power before and
      after KRS from the preoperative measured keratometry. As a second option, we
      demonstrate in the paper how to derive the respective values from the
      postoperative (instead of the preoperative) measured keratometry. EXAMPLE:
      Initial refraction before/after KRS, -12.0/-2.0 D; corneal thickness, 550/440
      microm; front/back surface power 48.20-5.81 D, measured Zeiss keratometry before
      KRS, 42.5 D. After KRS, we calculate a corneal front surface power of 39.82 D and
      an equivalent/back vertex power and keratometry of 34.08/34.48/35.11 D (result of
      the "Clinical History Method" at spectacle/corneal plane 32.50/33.96 D).
      Calculated corneal power values are around 2-3 D lower than measured Zeiss
      keratometry (37.0 D), which will lead to an IOL power overestimation of about 3-4
      D and subsequent hyperopia. CONCLUSIONS: This formalism may help to prevent
      hyperopia after cataract surgery subsequent to refractive surgery for myopia.

PMID- 17514528
TI  - Corneal higher-order aberrations after customized aspheric ablation and
      conventional ablation for myopic correction.
AB  - PURPOSE: To investigate and compare the corneal wavefront aberrations and corneal
      asphericity after customized aspheric and conventional myopic ablation. METHODS:
      Fifty-eight myopic patients from two laser centers were enrolled in this study.
      The patients were treated with laser in situ keratomileusis (LASIK) randomly with
      customized aspheric algorithm (32 patients, group A) and conventional algorithm
      (26 patients, group B). There was no significant difference in preoperative mean
      equivalent sphere (p = 0.954). The manifest refraction, corneal asphericity, and
      corneal wavefront data were taken into account to generate the customized
      aspheric ablation profile. Corneal wavefront aberrations, and corneal asphericity
      were analyzed and compared before and 6 months after the treatment. RESULTS:
      Preoperatively, no significant difference was found in corneal asphericity and
      higher-order aberrations (HOAs) between two groups (p = 0.833 and p = 0.459,
      respectively). Root mean square (RMS) value of corneal HOAs, spherical
      aberration, and corneal asphericity increased postoperatively in both groups (p <
      0.05), but the smaller increase was shown in group A (p < 0.05). The Zernike
      third-order aberration increased by 10% (p = 0.088) but without significance in
      group A compared with significant increase by 27% (p < 0.01) in group B.
      CONCLUSIONS: The customized aspheric ablation induced smaller increase in corneal
      higher-order aberrations and corneal asphericity. It provides a good option for
      the customized myopic correction.

PMID- 17514529
TI  - Delay of cataract development in the Shumiya cataract rat by water containing
      enhanced concentrations of magnesium and calcium.
AB  - We demonstrate a delaying effect of deep-sea drinking water (DDW) containing
      enhanced magnesium ion (Mg(2 +)) and calcium ion (Ca(2 +)) concentrations on
      cataract development in Shumiya cataract rats (SCRs). The lenses of SCRs
      administered DDW-200 (Mg(2 +), 200 mg/L, Ca(2 +); 71 mg/L) were less opaque than
      those in SCRs administered purified water (PW). In SCRs administered DDW-200, a
      decrease in Mg(2 +) content and an increase in Ca(2 +) content in the lenses was
      prevented in comparison with SCRs administered PW. Nitric oxide (NO) levels in
      the lenses of SCRs administered DDW-200 were lower than those in SCRs
      administered PW. In conclusion, the administration of DDW-200 to SCRs has a
      potent delaying effect on cataract development, possibly due to preventing an
      increase in NO levels in the lens.

PMID- 17514530
TI  - Glutathione-S-transferase M1 and T1 genetic polymorphisms and the risk of
      cataract development: a study in the Turkish population.
AB  - In this study, we aimed to determine the effects of genetic polymorphisms of
      glutathione-S-transferase M1 (GSTM1) and glutathione-S-transferase T1 (GSTT1) on
      risk of developing different subtypes of age-related cataract in the Turkish
      population. Using a multiplex polymerase chain reaction (PCR), GSTM1 and GSTT1
      gene polymorphisms were analyzed in 195 patients with age-related cataract (75
      patients with cortical, 53 with nuclear, 37 with posterior subcapsular, and 30
      with mixed type) and in 136 patients of an otherwise healthy control group of
      similar age. GSTM1 null genotype had a significant association with the
      development of cataract in female subjects (p < 0.0029; OR, 2.98; 95% CI, 1.41
      6.34). This relationship in female subjects was only in nuclear and mixed types
      cataract cases (p < 0.002; OR, 4.58; 95% CI, 1.67-12.78 and p < 0.03,
      respectively). There was also a statistically significant association between the
      combination of GSTM1-null and GSTT1-positive genotypes and the risk of cataract
      development in female subjects (p = 0.01; OR = 2.87; 95% CI = 1.25-6.69).
      Stratification by the subtypes revealed that this association was only in nuclear
      type cataract (p = 0.001; OR, 3.92; 95% CI, 1.34-11.71). GSTM1-null genotype or
      combination of the GSTM1-null and GSTT1-positive genotypes in females may be
      associated with increased risk of cataract development in the Turkish population.

PMID- 17514531
TI  - Revival of glutathione reductase in human cataractous and clear lens extracts by
      thioredoxin and thioredoxin reductase, in conjunction with alpha-crystallin or
      thioltransferase.
AB  - Glutathione reductase (GR) plays a key role in maintaining thiol groups in the
      lens, and its activity decreases with aging and cataract formation. Mammalian
      thioredoxin (Trx) and thioredoxin reductase (TrxR), or the Trx/TrxR system,
      participates in the repair of oxidatively damaged lens proteins and enzymes.
      Alpha-crystallin, a molecular chaperone, prevents the aggregation of partially
      denatured proteins under various stress conditions. Thioltransferase (TTase, or
      glutaredoxin) can maintain the homeostasis of lens protein thiols thus protecting
      against oxidative stress. We investigated whether the Trx/TrxR system can revive
      GR activity in both the cortex and nucleus of human cataract and clear aged
      lenses and whether alpha-crystallin and TTase can help this effect. The GR
      activity in the cortex and nucleus of the cataractous lenses was significantly
      lower than that of the aged clear lenses. The highest activity in the cortex was
      observed in the clear aged lenses. The combination of Trx and TrxR revived the
      activity of GR from both the cortex and nucleus of aged clear lenses. However, in
      cataract lenses (grade II and grade IV), there was a statistically significant
      recovery of GR activity in the cortex, but not in the nucleus. No recovery was
      observed when Trx or TrxR were used separately. Alpha-crystallin successfully
      revived GR activity in the cortex of cataract grade II lenses, but not in the
      nucleus. The combination of alpha-crystallin and Trx/TrxR gave a further increase
      of activity. TTase alone revived some of the GR activity but together with the
      Trx/TrxR system gave no statistically significant enhancement of GR activity.
      These results indicate that both disulfide bond formation and protein unfolding
      are responsible for GR inactivation.

PMID- 17514532
TI  - Effects of storage time on the mechanical properties of rabbit peripapillary
      sclera after enucleation.
AB  - In the field of biomechanics, little research has been performed to evaluate the
      effect of storage time on the material properties of ocular tissues. Twenty-four
      rabbit eyes were divided into six groups with storage times from 3 to 72 hr. A
      tensile specimen was prepared from the inferior quadrant of each sclera and was
      subjected to a stress relaxation test. The data were analyzed using linear
      viscoelastic theory yielding four material parameters (E(0), instantaneous
      elastic modulus; E(infinity), equilibrium elastic modulus; beta, half-width of
      the Gaussian distribution; tau(m); mean relaxation time). No statistically
      significant differences were found in the material properties of each group,
      which suggests that sclera can be stored up to 3 days without risking mechanical
      deterioration.

PMID- 17514533
TI  - Intraperitoneal injection of Ginkgo biloba extract enhances antioxidation ability
      of retina and protects photoreceptors after light-induced retinal damage in rats.
AB  - PURPOSE: To investigate the effect of Ginkgo biloba extract EGb 761, a free
      radical scavenger, on the antioxidation capability of retina after light-induced
      retinal damage in rats in an attempt to understand the mechanism by which EGb 761
      protects the photoreceptors after light-induced retinal damage. METHODS: Seventy
      two female Sprague-Dawley (SD) rats were evenly randomized into normal control
      group (NC group), light-induced retinal damage model group (M group), model +
      normal saline group (MN group), and model + EGb 761 group (ME group). Light
      induced retinal damage model was induced via exposure to white light at 2740 +/-
      120 lux for 6 hr. Rats in MN group and ME group were intraperitoneally injected
      daily with normal saline and 0.35% EGb 761 (100 mg/kg), respectively, 1 week
      before and 2 weeks after light exposure. The levels of malondialdehyde (MDA),
      total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase
      (CAT) in the retinal tissues were determined 24 hrs after light exposure;
      photoreceptor apoptosis was detected 4 days after light exposure. One and 2 weeks
      after light exposure, histopathologic examination was carried out, and the outer
      nuclear layer (ONL) thickness (number of nuclei) in the superior and inferior
      retina was counted. RESULTS: Twenty-four hours after exposure, the MDA levels in
      the other three groups were significantly higher than that in the NC group (p <
      0.05); those in the M and MN groups were similar to each other (p > 0.05); and
      that of the ME group was significantly lower than those in the M and MN group (p
      < 0.05). The activities of T-SOD, GSH-Px, and CAT were similar in the M and MN
      groups (p > 0.05); the activities in the M and MN groups were significantly lower
      than those in the NC and ME groups (p < 0.05); and the activities in the ME group
      were significantly higher than those in the M and MN groups (p < 0.05). Four days
      after exposure, the apoptotic photoreceptors within the ONL in the ME group were
      obviously fewer than those in the M and MN groups. One week and 2 weeks after
      exposure, the ONL thickness (number of nuclei) in the ME group was more than that
      in the M and MN groups but less than that in the NC group. CONCLUSIONS:
      Intraperitoneal injection of EGb 761 can enhance the antioxidation ability of
      retina and partially inhibit the apoptosis of photoreceptors, thus exert a
      protective effect on photoreceptors.

PMID- 17514535
TI  - Fate of deoxynivalenol in contaminated wheat grain during preparation of Egyptian
      'balila'.
AB  - Soaking and boiling whole wheat kernels in water are the key steps in the
      preparation of an Egyptian dish called 'balila'. The effects of washing, soaking
      and boiling wheat kernels in tap water or in 0.1 M Na2CO3 solution on the
      deoxynivalenol (DON) content of the wheat kernels were studied. Boiling
      contaminated wheat kernels in water reduced the DON content of the grain by 70%.
      The mechanism of decontamination due to boiling is probably a leaching of DON out
      of the grain into the boiling medium. A combined treatment of soaking in 0.1 M
      Na2CO3 solution (pH 11) with subsequent boiling reduced the DON content of the
      grain by 93%. Data suggest that apart from leaching DON out of the kernels into
      the boiling medium, a degradation of DON occurred in alkaline medium. Modifying
      the traditional process of 'balila' preparation by using Na2CO3 solution may be
      useful to reduce the risk of mycotoxin exposure via 'balila'.

PMID- 17514536
TI  - Antioxidant and antimicrobial activities of native Rosa sp. from British
      Columbia, Canada.
AB  - Indigenous traditional knowledge and western science have revealed the potential
      for significant nutritional and therapeutic benefits among natural antioxidants.
      We investigated antioxidant and antimicrobial activity of rose hip extracts (Rosa
      nutkana, Rosa pisocarpa and Rosa woodsii) from wild British Columbia populations
      using liposome oxidation and disc diffusion assays. All extracts exhibited strong
      antioxidant activity. R. nutkana pericarp extracts contained high phenolic
      concentrations and showed greater antioxidant and antimicrobial activity than
      seed extracts. R. woodsii seed extracts had a higher phenolic concentration and
      greater antioxidant activity than pericarp extracts. Antioxidant activity was
      correlated with antimicrobial activity, and both extracts showed antimicrobial
      activity against yeast and Gram-positive bacteria. Our study is the first to
      demonstrate the antioxidant and antimicrobial properties of wild British Columbia
      roses. The effectiveness of selected species compared with standards demonstrates
      the significance of this natural resource to the continued health of human
      populations, and the need for conservation practices.

PMID- 17514537
TI  - Regular peanut consumption improves plasma lipid levels in healthy Ghanaians.
AB  - OBJECTIVE: To determine whether the daily intake of 2,092 kJ (500 kcal) from
      peanuts will improve the lipid profiles and diet quality of healthy Ghanaians.
      DESIGN: A 30-week, randomized, cross-over trial study was conducted with healthy
      adults. METHOD: There were three treatment arms: Treatment 1 (T1), subjects were
      provided 2,092 kJ/day (500 kcal/day) peanuts to incorporate into their daily diet
      for 8 weeks at any time and in any form they chose; Treatment 2 (T2), subjects
      were provided 2,092 kJ/day (500 kcal/day) peanuts and were instructed to consume
      them in addition to their customary daily diet for 3 weeks; Treatment 3 (T3),
      substitution of 2,092 kJ/day fat, with energy from peanuts. Total cholesterol,
      high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and
      triglyceride were measured at baseline, week 4 and week 8 (T1 and T3) or at
      baseline and week 3 (T2). Three-day dietary intake records were kept during each
      treatment. RESULTS: There was significant decrease in total cholesterol (7.2%)
      and triacylglycerol (20.0%) after T1. However, individually, high-density
      lipoprotein-cholesterol and low-density lipoprotein-cholesterol levels did not
      change significantly. Total fat intake increased by 9%, due to elevations of
      monounsaturated fatty acid of 60% and polyunsaturated fatty acid of 50%. Similar
      non-significant trends were observed during T2 and T3. CONCLUSION: The results
      suggest that regular consumption of peanuts lowers the total cholesterol and
      triacylglycerol concentrations among healthy Ghanaians. Regular consumption of
      peanuts should therefore be encouraged.

PMID- 17514538
TI  - Breakfast and the diets of Australian children and adolescents: an analysis of
      data from the 1995 National Nutrition Survey.
AB  - The aim of this study was to describe the nutrients provided to Australian
      children and adolescents by the breakfast meal and compare the food and nutrient
      intakes and health of regular breakfast eaters (those who ate breakfast 5 days or
      more a week) and skippers (who are breakfast rarely or never). The Australian
      Bureau of Statistics was commissioned to undertake additional analysis of data
      collected in the 1995 Australian National Nutrition Survey. The survey included
      24-h recalls, physical measurements and a food-habits questionnaire collected
      during the period February 1995-March 1996, with a nationally representative
      sample of 3,007 Australians aged between 2 and 18 years. The median nutrient
      intakes at breakfast and the proportion of the daily total contributed by
      breakfast were calculated. Differences between regular breakfast eaters and
      breakfast skippers in terms of nutrient intake, body mass index and health status
      were compared using student t-tests. The findings show the typical breakfast
      consumed by young Australians was low in fat, high in carbohydrate and a good
      source of thiamin, riboflavin, niacin, calcium and magnesium. Those who did not
      eat breakfast cereal were much more likely to have inadequate nutrient intakes,
      especially of thiamin, riboflavin, calcium, magnesium and iron. There was no
      difference between the fat intake and the body mass index of regular breakfast
      eaters compared with breakfast skippers. Regular breakfast consumption is
      associated with better diets for children and adolescents.

PMID- 17514539
TI  - Weight control among obese adolescents: a pilot study.
AB  - OBJECTIVE: The present study evaluated weight loss and compliance outcomes for
      overweight adolescents assigned to one of two dietary interventions differing in
      the type of snacks allowed. METHODS: The study was a 12-week, controlled clinical
      trial, among otherwise healthy but overweight (body mass index >or=95th
      percentile) 11-year-old to 15-year-old girls who were randomly assigned to either
      a 1,500 kcal/day free-snack program or a 1,500 kcal/day restricted-snack program.
      All subjects were counseled to consume three servings of dairy products per day,
      and were provided with a 500 mg calcium supplement as well. Subjects in the free
      snack group could choose any 150-calorie item as one of their two daily snacks,
      including regular soda if desired; however, subjects in the restricted-snack
      group were limited to diet soda. RESULTS: Thirty-two adolescent girls completed
      the 12-week intervention. Both diets were equally effective in achieving a modest
      amount of weight loss, and were equally acceptable to the subjects. Significant
      decreases in weight, body mass index, anthropometric measures, total cholesterol
      and triglycerides were observed. CONCLUSIONS: A 1,500 kcal/day diet allowing for
      a free snack of 150 calories was equally as effective as a more restricted snack
      policy in achieving a modest amount of weight loss among overweight 11-year-old
      to 15-year-old girls. In addition, results suggest that some soda may be included
      in a teen weight control diet, as long as caloric intake is maintained at
      recommended levels, and care is taken to achieve adequate intake of essential
      nutrients. Calcium intake among subjects was low at baseline, and, although it
      increased during the study (due to supplementation), further efforts to increase
      consumption of naturally calcium-rich and calcium-fortified foods and beverages
      are needed.

PMID- 17514540
TI  - Iodine content in bread and salt in Denmark after iodization and the influence on
      iodine intake.
AB  - OBJECTIVE: To measure the iodine content in bread and household salt in Denmark
      after mandatory iodine fortification was introduced and to estimate the increase
      in iodine intake due to the fortification. DESIGN: The iodine content in rye
      breads, wheat breads and salt samples was assessed. The increase in iodine intake
      from fortification of bread and the increase in total iodine intake after
      fortification were estimated. SUBJECTS: Iodine intake before and after
      fortification was estimated based on dietary intake data from 4,124 randomly
      selected Danish subjects. MAIN RESULTS: Approximately 98% of the rye breads and
      90% of the wheat breads were iodized. The median iodine intake from bread
      increased by 25 (13-43) microg/day and the total median iodine intake increased
      by 63 (36-104) microg/day. CONCLUSIONS: The fortification of bread and salt has
      resulted in a desirable increase in iodine intake, and the current fortification
      level of salt (13 ppm) seems reasonable.

PMID- 17514541
TI  - Teaching phoneme awareness to pre-literate children with speech disorder: a
      randomized controlled trial.
AB  - BACKGROUND: Awareness of individual phonemes in words is a late-acquired level of
      phonological awareness that usually develops in the early school years. It is
      generally agreed to have a close relationship with early literacy development,
      but its role in speech change is less well understood. Speech and language
      therapy for children with speech disorder involves tasks that appear, either
      implicitly or explicitly, to require a phonemic level of awareness. However,
      children typically attend for intervention at a pre-school, pre-literate stage,
      i.e. before they would be expected to have developed the relevant phoneme
      segmentation and manipulation skills. AIMS: To investigate whether it is possible
      to teach phoneme awareness skills to pre-literate children with speech disorder.
      METHODS & PROCEDURES: In a randomized controlled trial design 42 children with
      speech disorder, aged 4;0-4;6, were allocated to either a phonological awareness
      or a language stimulation programme. Children were assessed on four measures of
      phoneme awareness (alliteration awareness, phoneme isolation, word segmentation
      and phoneme addition/deletion) immediately before and after the programme and
      categorized as 'improved' or 'not improved' according to predetermined criteria.
      Fisher's Exact test was used to compare outcome in the two groups. OUTCOMES &
      RESULTS: Significantly more children improved in the phonological awareness group
      than in the language stimulation group for three out of the four measures (all
      except alliteration awareness). However, for the two most advanced tasks
      (segmentation and addition/deletion) only a small minority of children showed
      improvement. A marked improvement in Phoneme Isolation was made by the majority
      of children in the phonological awareness group. CONCLUSIONS: It is possible to
      teach some advanced phoneme awareness skills to some pre-literate children.
      Phoneme Isolation was the most easily learned and is a skill that appears very
      relevant to speech and language therapy. However, phoneme addition, deletion and
      word segmentation showed relatively limited improvement and only in a small
      number of cognitively able and older children. Whereas isolation of word initial
      consonants appears to be a skill that can be triggered at 4;0-4;6 by relevant
      activities, most children in the study were not cognitively ready for more
      advanced, abstract phoneme manipulation tasks. This raises questions about how
      speech and language therapists should tackle many common errors and the age at
      which we should aim to develop or draw on phoneme awareness to stimulate speech
      change.

PMID- 17514542
TI  - Aetiological relationship between language performance and autistic-like traits
      in childhood: a twin study.
AB  - BACKGROUND: Impairments in language and communication are core features of autism
      spectrum disorders (ASDs). The basis for this association is poorly understood.
      How early language is related to each of the triad of impairments characteristic
      of ASDs is also in need of clarification. AIMS: This is the first study that aims
      to determine the extent to which shared genetic and environmental factors
      underlie the association between early language performance and autistic-like
      traits (ALTs) in middle childhood. METHODS & PROCEDURES: Data came from a
      population-based twin sample (n = 6087 pairs) assessed prospectively at 2, 3, 4
      and 8 years. ALTs measured by the Childhood Asperger Syndrome Test (CAST) at 8
      years were investigated in relation to language assessed by the MacArthur
      Communicative Development Inventory (CDI) at 2, 3 and 4 years. Multivariate model
      fitting techniques were used to analyse the origins of this association. OUTCOMES
      & RESULTS: Total CAST scores, as well as Social and Communication subscales, at 8
      years were weakly but significantly negatively correlated with language ability
      at 2, 3 and 4 years. Correlations between language and restrictive and repetitive
      behaviours and interests (RRBI) were not significant. The phenotypic correlations
      between language and Social and Communication ALTs were almost entirely mediated
      by shared genetic influences. There were specific genetic influences on early
      language that were not shared with ALTs, and specific genetic influences on ALTs
      not shared with earlier language performance. CONCLUSIONS: This is the first
      study to demonstrate shared genetic influences in relation to language
      performance as an early antecedent of later ALTs. These results support the idea
      that the triad of core features in ALTs are aetiologically heterogeneous, with
      early language relating to social and communication impairments but not RRBIs.

PMID- 17514543
TI  - Subject-verb agreement and phonological processing in developmental dyslexia and
      specific language impairment (SLI): a closer look.
AB  - BACKGROUND: Problems with subject-verb agreement and phonological (processing)
      skills have been reported to occur in children with specific language impairment
      (SLI) and in those with developmental dyslexia, but only a few studies have
      compared such problems in these two groups. Previous studies have claimed a
      causal relationship between phonological processing deficits and morphosyntactic
      problems. AIMS: The following questions were addressed in this study: (1) Are
      children with developmental dyslexia and SLI comparable in the level of
      sensitivity to subject-verb agreement, phonological awareness, and non-word
      repetition? (2) Are children with developmental dyslexia and SLI comparable in
      their performance profiles on tasks tapping subject-verb agreement, phonological
      awareness, and non-word repetition? (3) Are deficits in phonological processing
      skills related to morphosyntactic deficits? METHODS & PROCEDURES: Forty-five
      children (mean age = 8;6 years) with developmental dyslexia, SLI and typically
      developing children participated. The sensitivity to subject-verb agreement,
      phonological awareness, and non-word repetition was measured. OUTCOMES & RESULTS:
      Both the children with dyslexia and with SLI made more errors than the control
      children on the subject-verb agreement task, with the children with dyslexia
      scoring significantly better than the children with SLI. Similarly, the children
      with SLI and dyslexia both performed more poorly on the phoneme-deletion task
      than the control group. Both clinical groups performed more poorly on the non
      word repetition task than the control children, with the children with dyslexia
      outperforming the children with SLI. In all three tasks differences in
      performance profiles were found between the children with developmental dyslexia
      and SLI. Across all three groups non-word repetition was correlated with
      morphosyntactic sensitivity. CONCLUSIONS: The results show similarities between
      the performances of children with SLI and dyslexia on tasks tapping subject-verb
      agreement, phonological awareness, and non-word repetition: they scored more
      poorly than typically developing children. Qualitative analyses revealed,
      however, differences in the error patterns on all three tasks. Associations
      between non-word repetition and sensitivity to subject-verb agreement were found,
      suggesting that problems with phonological processing impact on morphosyntactic
      skills.

PMID- 17514544
TI  - Can a 'single hit' cause limitations in language development? A comparative study
      of Swedish children with hearing impairment and children with specific language
      impairment.
AB  - BACKGROUND: Studies of language in children with mild-to-moderate hearing
      impairment (HI) indicate that they often have problems in phonological short-term
      memory (PSTM) and that they have linguistic weaknesses both in vocabulary and
      morphosyntax similar to children with specific language impairment (SLI).
      However, children with HI may be more likely than children with SLI to acquire
      typical language skills as they get older. It has been suggested that the more
      persisting problems in children with SLI are due to a combination of factors:
      perceptual, cognitive and/or linguistic. AIMS: The main aim of this study was to
      explore language skills in children with HI in comparison with children with SLI,
      and how children with both HI and language impairment differ from those with non
      impaired spoken language skills. METHODS & PROCEDURES: PSTM, output phonology,
      lexical ability, receptive grammar and verb morphology were assessed in a group
      of children with mild-to-moderate HI (n = 11) and a group of children with SLI (n
      = 12) aged 5 years 6 months to 9 years 0 months. OUTCOMES & RESULTS: The HI group
      tended to score higher than the SLI group on the language measures, although few
      of the differences were significant. The children with HI had their most obvious
      weaknesses in PSTM, vocabulary, receptive grammar and inflection of novel verbs.
      The subgroup of children with HI (five out of 10) who also showed evidence of
      grammatical output problems was significantly younger than the remaining children
      with HI. Correlation analysis showed that the language variables were not
      associated with age, whereas hearing level was associated with PSTM. CONCLUSIONS:
      Children with HI are at risk for at least a delay in lexical ability, receptive
      grammar and grammatical production. The problems seen in the HI group might be
      explained by their low-level perceptual deficit and weak PSTM. For the SLI group
      the impairment is more severe. From a clinical perspective an important
      conclusion is that the language development in children with even mild-to
      moderate HI deserves attention and support.

PMID- 17514545
TI  - Influence of phonology on morpho-syntax in Romance languages in children with
      Specific Language Impairment (SLI).
AB  - BACKGROUND: The profiles of children with Specific Language Impairment (SLI)
      differ greatly according to the language they speak. The Surface Hypothesis
      attempts to explain these differences through the theory that children with SLI
      will incorrectly produce elements in their language with low phonological weights
      or that are produced in a non-canonical prosodic structure. AIMS: Previous
      studies have shown that the most characteristics errors produced by Catalan and
      Spanish-speaking children with SLI include function word omission (morpho-syntax)
      and weak syllable omission (phonology). The omission of function words points to
      a morpho-syntactic explanation of SLI, while weak syllable omission supports a
      phonological explanation of SLI. Yet, function words are weak syllables; thus, it
      is possible that the same mechanism underlies both problems. METHODS &
      PROCEDURES: Data were extracted from spontaneous language produced by five
      children with SLI and five comparison children matched for age and MLU-w. They
      were assessed on two occasions: at 3;10 and 4;9 years of age. These interviews
      were then transcribed and the morphological and phonological errors coded. A non
      parametric mean analysis and various regression analyses were conducted. OUTCOMES
      & RESULTS: The results show that function word omission and weak syllable
      omission were the most characteristic errors made by Spanish and Catalan-speaking
      children with SLI and established that omissions increase as prosodic weight
      decreases. They also indicated that weak syllabic omission may explain most
      function word omissions. CONCLUSIONS & IMPLICATIONS: The data support the Surface
      Hypothesis and suggest that the same impaired mechanism may underlie the
      morphological and phonological problems SLI children display.

PMID- 17514546
TI  - Counting span and the identification of primary language impairment.
AB  - BACKGROUND: In recent research, verbal working memory has been proposed as a
      primary area of deficit for children with language impairment (LI), and therefore
      a source of more sensitive assessment measures. In addition, research on non
      linguistic tasks has suggested that children with LI may have deficits that
      extend beyond the linguistic domain. These dual lines of research can be
      connected to the drive for non-biased assessment tasks for children with diverse
      language learning experiences (such as bilingual children), because linguistic
      tasks may be intrinsically biased against such children. AIMS: To investigate the
      usefulness of a working-memory task with a minimal linguistic load as a potential
      screening tool for children with primary LI. METHODS & PROCEDURES: Three groups
      of children aged 7;10-13;11 participated in the study: monolingual English
      speaking children with LI, typical monolingual English-speaking children, and
      typical Spanish-English bilingual children with several years of English
      experience. Performance of the three groups on the Counting Span task was
      explored through group comparisons and likelihood ratios. OUTCOMES & RESULTS:
      Children with LI had significantly lower Counting Span Set score accuracy than
      either typical group, with the monolingual and bilingual groups showing
      equivalent task performance. However, results from likelihood ratios showed that
      Counting Span accuracy did not have compelling diagnostic power when the entire
      age group was considered. Children with less than 67% accuracy were only three
      times more likely to be from the LI group than from either of the two typical
      groups. In addition to language status (typical or LI), chronological age was a
      key contributor to Counting Span performance in this age group. Likelihood ratios
      for children aged 10;0 and above showed that children with less than 67% accuracy
      were nine times more likely to come from the LI group than the typical groups.
      CONCLUSIONS: This intermediate diagnostic ability suggests that performance on
      the Counting Span alone is insufficient to identify LI among linguistically
      diverse learners. However, Counting Span may be a very useful component of a
      larger LI assessment battery, particularly for children over the age of 10;0.

PMID- 17514547
TI  - Long- and short-term results of children's and adolescents' therapy courses for
      stuttering.
AB  - BACKGROUND: It is widely known that most young children recover from stuttering.
      Evaluations of this spontaneous recovery vary from 40 to 80% of stuttering
      children. However, if the child is already older than 6 years of age, the
      spontaneous recovery will be less likely. The effectiveness of stuttering
      treatment, and especially fluency shaping methods, has been frequently studied.
      Good results in the treatment of stuttering for school-aged children have been
      accomplished by several treatment methods. However, stuttering modification
      treatments have not been studied so intensively. AIMS: This study addresses the
      effects of intensive therapy courses on the stuttering behaviour of children and
      adolescents. The courses included speech therapy, where stuttering modification
      treatment was used, and also parental guidance. METHODS & PROCEDURES: Taking part
      in the study were 21 children/adolescents who stutter, and 29 of their
      mothers/fathers took part in the study. The children were between the ages of 6.8
      and 14.0 years. The effectiveness of therapy was evaluated in three ways. First,
      the speech of the children who stutter was videotaped at both the beginning and
      the end of the course and the samples were transcribed and analysed. Second, the
      parents and adolescents completed a feedback questionnaire at the end of the
      course. And third, the parents and adolescents completed a follow-up
      questionnaire 9 months after the course. The aim was to evaluate the changes in
      stuttering behaviour after the therapy course. OUTCOMES & RESULTS: The results
      indicate that stuttering severity became milder or did not change during the
      course. The percentage of syllables stuttered dropped with two-thirds of the
      participants. This result was replicated with avoidance behaviour and struggle
      behaviour. The quality of stuttering became milder, and by the end many children
      had shorter moments of stuttering and more repetitions and prolongation instead
      of blocks. Two participants did not complete the questionnaire. Of those who did,
      all but one adolescent, and all except one parent, reported that the positive
      changes in stuttering behaviour had continued during the follow-up period.
      CONCLUSIONS: The implication is that intensive therapy courses can be helpful to
      some participants who stutter.

PMID- 17514552
TI  - Cybermedicine tools for communication and learning.
AB  - The medical domain provides excellent opportunities for communication and
      teaching of healthcare issues using computer graphics, visualization techniques,
      and virtual environments. Possible applications include anatomical educational
      tools; patient education; diagnostic aids; virtual autopsies; planning and
      guidance aids; skills training; and computer augmented reality. Both clinicians
      and patients can benefit from the appropriate use of tools that make use of these
      technologies. This paper provides an overview of the state-of-the-art
      technologies in this exciting field, including detailed examples from our
      research. The term cybermedicine is discussed and issues for effective
      cybermedicine are highlighted.

PMID- 17514553
TI  - Digital imaging in the forensic post-mortem room.
AB  - This paper describes the development of a specialist forensic post-mortem room,
      complete with digital imaging facilities, by the Institute of Forensic Medicine
      at the University Hospital of Wales, Cardiff. It gives the background to the
      development of the facility, and briefly details the specifications before
      discussing the use of digital imaging in evidence and the need for a full-time
      specialist forensic medical photographer.

PMID- 17514554
TI  - 'In camera': photographing forensic medicine and science c. 1920-1940.
AB  - This article outlines the photographic sources held in the historical case file
      generated by the University of Glasgow's Department of Forensic Medicine and
      Science and by two of its former Regius Professors, John Glaister Senior (1856
      1932) and John Glaister Juniour (1892-1971). The contexts in which photographs
      were taken circulated and used, from scenes of crime, to the laboratory and the
      courtroom will be explored in relation to some of the Glaisters' individual cases
      to some of Scotland's most notorious crimes.

PMID- 17514557
TI  - Supporting patients.

PMID- 17514559
TI  - Clinical photography in wound management.
AB  - The IMI National Guidelines have been prepared as baseline guides on specific
      aspects of medical illustration practice, and provide auditable standards for the
      future. They can be implemented in full, or may be amended according to
      individual requirements. The following is an abridged version of guidelines
      prepared by Carol Fleming. The full version, including references and appendices,
      can be downloaded at www.imi.org.uk.

PMID- 17514564
TI  - Endocrine disruption profile analysis of 11,416 chemicals from chemometrical
      tools.
AB  - A number of chemicals released into the environment have the potential to disturb
      the normal functioning of the endocrine system. These chemicals termed endocrine
      disruptors (EDs) act by mimicking or antagonizing the normal functions of natural
      hormones and may pose serious threats to the reproductive capability and
      development of living species. Batteries of laboratory bioassays exist for
      detecting these chemicals. However, due to time and cost limitations, they cannot
      be used for all the chemicals which can be found in the ecosystems. SAR and QSAR
      models are particularly suited to overcome this problem but they only deal with
      specific targets/endpoints. The interest to account for profiles of endocrine
      activities instead of unique endpoints to better gauge the complexity of
      endocrine disruption is discussed through a SAR study performed on 11,416
      chemicals retrieved from the US-NCI database and for which 13 different PASS
      (Prediction of Activity Spectra for Substances) endocrine activities were
      available. Various multivariate analyses and graphical displays were used for
      deriving structure-activity relationships based on specific structural features.

PMID- 17514565
TI  - How can structural similarity analysis help in category formation?
AB  - Chemical category is a regulatory concept facilitating filling safety data gaps.
      Practically, all chemical management programs like the OECD HPV Program, EU
      REACH, or the Canadian DSL Categorization are planning to use or are already
      using categorization approaches to reduce resources including animal testing. The
      aim of the study was to discuss the feasibility to apply computational structural
      similarity methods to augment formation of a category. The article discusses also
      how this understanding can be translated into computer readable format, an
      ultimate need for practical, broad scope applications. We conclude that for the
      skin sensitization endpoint, used as a working example, mechanistic understanding
      expressed as chemical reactivity can be exploited by computational structural
      similarity methods to augment category formation process. We propose a novel
      method, atom environments ranking (AER), to assess similarity to a reference
      training set representing a common mechanism of action, as a potential method for
      grouping chemicals into reactivity domains.

PMID- 17514566
TI  - The specificity of the QSAR models for regulatory purposes: the example of the
      DEMETRA project.
AB  - QSAR models have special characteristics depending on the field they are
      addressing. In the case of QSAR models for regulatory purposes particular
      requirements should be introduced, to warrant the proper use within a regulatory
      context. Here the criteria introduced within the European project DEMETRA are
      presented and discussed. The case discussed here refers to models addressing
      (eco)toxicological endpoints. Major issues are related to the identification of
      regulation guidelines, data quality and reproducibility. Further points to be
      addressed in the model description should be uncertainty and availability of the
      model, and false negatives, even in the case of regression models.

PMID- 17514567
TI  - Evaluation of SARs for the prediction of eye irritation/corrosion potential:
      structural inclusion rules in the BfR decision support system.
AB  - The proposed REACH regulation within the European Union (EU) aims to minimise the
      number of laboratory animals used for human hazard and risk assessment while
      ensuring adequate protection of human health and the environment. One way to
      achieve this goal is to develop non-testing methods, such as (quantitative)
      structure-activity relationships ([Q]SARs), suitable for identifying
      toxicological hazard from chemical structure and physicochemical properties
      alone. A database containing data submitted within the EU New Chemicals
      Notification procedure was compiled by the German Bundesinstitut fur
      Risikobewertung (BfR). On the basis of these data, the BfR built a decision
      support system (DSS) for the prediction of several toxicological endpoints. For
      the prediction of eye irritation and corrosion potential, the DSS contains 31
      physicochemical exclusion rules evaluated previously by the European Chemicals
      Bureau (ECB), and 27 inclusion rules that define structural alerts potentially
      responsible for eye irritation and/or corrosion. This work summarises the results
      of a study carried out by the ECB to assess the performance of the BfR structural
      rulebase. The assessment included: (a) evaluation of the structural alerts by
      using the training set of 1341 substances with experimental data for eye
      irritation and corrosion; and (b) external validation by using an independent
      test set of 199 chemicals. Recommendations are made for the further development
      of the structural rules in order to increase the overall predictivity of the DSS.

PMID- 17514568
TI  - Three dimensional structure-activity relationships (3D-QSAR) for insect
      repellency of diastereoisomeric compounds: a hierarchical molecular overlay
      approach.
AB  - 2-(2-Hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester (Picaridin),
      and 1-(cyclohex-3-ene-1-ylcarbonyl)-2-methylpiperidine (AI3-37220; 220) are
      alternatives to DEET (N,N-diethyl-3-methylbenzamide), the most popular mosquito
      repellent. Picaridin and AI3-37220 exhibit polychiral diastereoisomerism and each
      has four diastereoisomers due to the presence of two asymmetric centers in their
      molecules. The diastereoisomers of these compounds have differing degrees of
      mosquito-repellent activity according to quantitative behavioral assays conducted
      at the United States Department of Agriculture. An insight into the
      stereochemical requirements for repellency is of great importance in the
      development of better repellents. Molecular overlay of the optimized geometries
      of the diastereoisomers was considered as a novel tool for Stereochemical
      Structure-Activity Relationship (SSAR) modeling. An earlier study using molecular
      mechanics (MM2) optimized geometries showed good promise. In continuation of this
      effort and to overcome certain defects in using MM2 geometries, a hierarchical
      overlay approach was developed. In this method geometry of the low energy
      conformer of each diastereoisomer was optimized using: the following quantum
      chemical methods in a graduated manner: (a) semiempirical AM1, (b) Hartree Fock
      (STO3G, 3-21G, 6-31G, and 6-311G), and (c) Density Functional Theory (B3LYP/6
      31G, B3LYP/6-311G). The optimized geometries of different diastereoisomers were
      overlaid in various user defined combinations to calculate the root mean square
      distances (RMSD) of the overlaid structures. The RMSD with respect to the most
      active diastereoisomer (220SS) were found to have a strong relationship with
      biological potency. Common motifs in shapes and molecular surfaces that are
      probably critical for effective repellent activity were identified. The
      hierarchical approach gave valuable information on the quantum chemical level
      (basis set) at which optimization must be carried out to get the correct order of
      repellency of the diastereoisomers of Picaridin and 220.

PMID- 17514569
TI  - QSAR of genotoxic active benzazoles.
AB  - Previously synthesized 2,5-disubstituted benzoxazole and benzimidazole
      derivatives, were tested for their genotoxic activity in the Bacillus subtilis
      rec- assay. The results revealed that 5-methyl-2-(p-aminobenzyl)benzoxazole
      exhibited the highest genotoxic response, which was comparable to 4
      nitroquinoline 1-oxide (4-NQO), the reference agent of classical positive
      mutagen. Among the other tested compounds, four showed a genotoxic activity. A
      QSAR study revealed that structural parameters IY(C(2)H(4)) and IY(CH(2)O),
      indicating the bridge elements between the phenyl moiety and the fused ring
      system at position 2 and the quantum chemical parameter (DeltaE ), showing the
      difference between HOMO and LUMO energies, were found significant for enhancing
      the genotoxic activity in these compounds. In addition, the substituent effects
      on positions R and R(1) were found important for the activity as well as holding
      a substituent possessing a maximum length with a minimum width property on
      position R(1) like alkyl groups. On the other hand, substituting position R with
      an electron donating group instead of electron withdrawing group increased the
      genotoxic activity.

PMID- 17514570
TI  - About the prediction of molecular properties using the fundamental Quantum QSPR
      (QQSPR) equation.
AB  - The present theoretical study analyses the Quantum QSPR fundamental linear
      equation predictive power. Two main alternative algorithms, among several
      possible choices, are fully described in an add one and add many basis, while the
      other possibilities are only sketched out. It is shown that one can also apply
      the described Quantum QSPR prediction algorithms to parent problems in the
      framework of empirical QSPR, based on the molecular space framework.

PMID- 17514571
TI  - A new approach to QSAR modelling of acute toxicity.
AB  - A new QSAR approach based on a Quantitative Neighbourhoods of Atoms description
      of molecular structures and self-consistent regression was developed. Its
      prediction accuracy, advantages and limitations were analysed from three sets of
      published experimental data on acute toxicity: 56 phenylsulfonyl carboxylates for
      Vibrio fischeri; 65 aromatic compounds for the alga Chlorella vulgaris and 200
      phenols for the ciliated protozoan Tetrahymena pyriformis. According to our
      findings, the proposed approach provides a good correlation and prediction
      accuracy (r(2) = 0.908 and Q(2) = 0.866) for the set of 56 phenylsulfonyl
      carboxylates and the 65 aromatic compounds tested on C. vulgaris (r(2) = 0.885,
      Q(2) = 0.849). For the 200 phenols tested on T. pyriformis, the prediction
      accuracy was r(2) = 0.685 and Q(2) = 0.651. This is at least as good as the best
      results obtained with the other QSAR methods originally used on the same data
      sets.

PMID- 17514572
TI  - Application and comparison of different chemometric approaches in QSPR modelling
      of supercooled liquid vapour pressures for chloronaphthalenes.
AB  - Molecular descriptors from calculations at the level of Density Functional Theory
      (B3LYP/6-311++G**) were effectively applied in QSPR estimation of supercooled
      liquid vapour pressures (P(L)) for individual chloronaphthalene congeners. The
      estimated values of log P(L) varied from 1.05 Pa to 5.6 x 10(-5) Pa, depending on
      the number of chlorine substituents present in the molecule and the substitution
      pattern. Comparison of the five chemometrical methods of modelling (approaches)
      led to the final conclusion, that the use of relatively simple PLS combined with
      one of the variable pre-selection algorithms (UVE or GA) seems to be the optimal
      choice in such computational studies for persistent organic pollutants. The best
      GA-PLS model was characterized by the value of root mean square error of
      prediction RMSEP = 0.108 logarithmic Pascal units.

PMID- 17514573
TI  - Scaling relationships based on partition coefficients and body sizes have
      similarities and interactions.
AB  - The LC(50) of compounds with a similar biological effect, at a given exposure
      period, is frequently plotted log-log against the octanol-water partition
      coefficient and a straight line is fitted for interpolation purposes. This is
      also frequently done for physiological properties, such as the weight-specific
      respiration rate, as function of the body weight of individuals. This paper
      focuses on the remarkable observation that theoretical explanations for these
      relationships also have strong similarities. Both can be understood as result of
      the covariation of the values of parameters of models of a particular type for
      the underlying processes, while this covariation follows logically from the model
      structure. The one-compartment model for the uptake and elimination of compounds
      by organisms is basic to the BioConcentration Factor (BCF), or the partition
      coefficient; the standard Dynamic Energy Budget model is basic to the (ultimate)
      body size. The BCF is the ratio of the uptake and the elimination rates; the
      maximum body length is the ratio of the assimilation (i.e. uptake of resources)
      and the maintenance (i.e. use of resources) rates. This paper discusses some
      shortcomings of descriptive approaches and conceptual aspects of theoretical
      explanations. The strength of the theory is in the combination of why metabolic
      transformation depends both on the BCF and the body size. We illustrate the
      application of the theory with several data sets from the literature.

PMID- 17514574
TI  - Evaluation of SARs for the prediction of skin irritation/corrosion potential:
      structural inclusion rules in the BfR decision support system.
AB  - The German Federal Institute for Risk Assessment (BfR) has developed a Decision
      Support System (DSS) to assess certain hazardous properties of pure chemicals,
      including skin and eye irritation/corrosion. The BfR-DSS is a rule-based system
      that could be used for the regulatory classification of chemicals in the European
      Union. The system is based on the combined use of two predictive approaches:
      exclusion rules based on physicochemical cut-off values to identify chemicals
      that do not exhibit a certain hazard (e.g., skin irritation/corrosion), and
      inclusion rules based on structural alerts to identify chemicals that do show a
      particular toxic potential. The aim of the present study was to evaluate the
      structural inclusion rules implemented in the BfR-DSS for the prediction of skin
      irritation and corrosion. The following assessments were performed: (a) a
      confirmation of the structural rules by rederiving them from the original
      training set (1358 substances), and (b) an external validation by using a test
      set of 200 chemicals not used in the derivation of the rules. It was found as a
      result that the test data set did not match the training set relative to the
      inclusion of structural alerts associated with skin irritation/corrosion, albeit
      some skin irritants were in the test set.

PMID- 17514575
TI  - Global (Q)SARs for skin sensitisation: assessment against OECD principles.
AB  - As part of a European Chemicals Bureau contract relating to the evaluation of
      (Q)SARs for toxicological endpoints of regulatory importance, we have reviewed
      and analysed (Q)SARs for skin sensitisation. Here we consider some recently
      published global (Q)SAR approaches against the OECD principles and present re
      analysis of the data. Our analyses indicate that "statistical" (Q)SARs which aim
      to be global in their applicability tend to be insufficiently robust
      mechanistically, leading to an unacceptably high failure rate. Our conclusions
      are that, for skin sensitisation, the mechanistic chemistry is very important and
      consequently the best non-animal approach currently applicable to predict skin
      sensitisation potential is with the help of an expert system. This would assign
      compounds into mechanistic applicability domains and apply mechanism-based
      (Q)SARs specific for those domains and, very importantly, recognise when a
      compound is outside its range of competence. In such situations, it would call
      for human expert input supported by experimental chemistry studies as necessary.

PMID- 17514576
TI  - Fruit Tree model for uptake of organic compounds from soil and air.
AB  - The current European risk assessment for chemicals considers only tap water,
      while in reality other beverages play an important role. A good part of beverages
      are made from fruits, for example apple juice and vine. A mathematical model was
      developed to predict uptake of neutral organic chemicals from soil and air into
      fruits. The new fruit tree model considers eight compartments, i.e. two soil
      compartments, fine roots, thick roots, stem, leaves, fruits, and air. Chemical
      equilibrium, advective transport in xylem and phloem, diffusive exchange to soil
      and air and growth dilution are the main processes. The parameterization is for a
      square-meter of an apple orchard. The model predicts that polar, non-volatile
      compounds will effectively be transported from soil to fruits, while lipophilic
      compounds will preferably accumulate from air into fruits. Results from various
      experiments show no disagreement with the model predictions.

PMID- 17514577
TI  - QSAR and mechanistic interpretation of estrogen receptor binding.
AB  - A multi-dimensional formulation of the COmmon REactivity PAttern (COREPA)
      modeling approach has been used to investigate chemical binding to the human
      estrogen receptor (hER). A training set of 645 chemicals included 497 steroid and
      environmental chemicals (database of the Chemical Evaluation and Research
      Institute, Japan - CERI) and 148 chemicals to further explore hER-structure
      interactions (selected J. Katzenellenbogen references). Upgrades of modeling
      approaches were introduced for multivariate COREPA analysis, optimal
      conformational generation and description of the local hydrophobicity of
      chemicals. Analysis of reactivity patterns based on the distance between
      nucleophilic sites resulted in identification of distinct interaction types: a
      steroid-like A-B type described by frontier orbital energies and distance between
      nucleophilic sites with specific charge requirements; an A-C type where local
      hydrophobic effects are combined with electronic interactions to modulate
      binding; and mixed A-B-C (AD) type. Chemicals were grouped by type, then COREPA
      models were developed for within specific relative binding affinity ranges of
      >10%, 10 > RBA > or = 0.1%, and 0.1 > RBA > 0.0%. The derived models for each
      interaction type and affinity range combined specific prefiltering requirements
      (interatomic distances) and a COREPA classification node using no more than 2
      discriminating parameters. The interaction types are becoming less distinct in
      the lowest activity range for each chemicals of each type; here, the modeling was
      performed within chemical classes (phenols, phthalates, etc.). The ultimate model
      was organized as a battery of local models associated to interaction type and
      mechanism.

PMID- 17514578
TI  - Festschrift for Dr. Richard Kvetnansky in celebration of his 70th birthday.

PMID- 17514579
TI  - Evolution of concepts of stress.
AB  - This essay describes the evolution of stress as a medical scientific idea. Claude
      Bernard, Walter B. Cannon and Hans Selye provided key founding concepts for the
      current view. Bernard introduced the idea of the internal environment bathing
      cells - the milieu interieur - maintained by continual compensatory changes of
      bodily functions. Cannon coined the word, "homeostasis," referring to a set of
      acceptable ranges of values for internal variables. Cannon taught that threats to
      homeostasis evoke activation of the sympathoadrenal system as a functional unit.
      Selye defined stress as a state characterized by a uniform response pattern,
      regardless of the particular stressor, that could lead to long-term pathologic
      changes. "Allostasis" was introduced as a concept in recognition that there is no
      single ideal set of steady-state conditions in life; instead, setpoints and other
      response criteria change continuously. Stress is now viewed neither as a
      perturbation nor a stereotyped response pattern but as a condition characterized
      by a perceived discrepancy between information about a monitored variable and
      criteria for eliciting patterned effector responses. Different stressors elicit
      different patterns of activation of the sympathetic nervous, adrenomedullary
      hormonal, hypothalamic-pituitary-adrenocortical and other effectors, closing
      negative feedback loops. This systems concept of stress yields predictions that
      observation or experimentation can test and that are applicable to normal
      physiology and to a variety of acute and chronic disorders.

PMID- 17514580
TI  - Stress-induced catecholaminergic function: transcriptional and post
      transcriptional control.
AB  - This review summarizes knowledge on the effects of stress on two catecholamine
      biosynthetic enzymes, tyrosine hydroxylase (TH) and phenylethanolamine N
      methyltransferase (PNMT). Information is presented on differential responses of
      the enzymes to a variety of stressors as well as differential responses of the
      enzymes localized to the central nervous system vs. peripheral nervous system and
      tissues. Changes in mRNA and protein or activity are described, including species
      and stressor-specific effects. While temporal changes in these parameters may
      differ for the particular stressor or enzyme, in general, maximal changes in mRNA
      and protein content occur at 6-8 and 24 h after stressor exposure, respectively.
      Elevation of TH and PNMT transcriptional activators prior to mRNA induction and
      nuclear run-on assays show that stress activates the genes encoding these
      enzymes. Yet, extents of induction of mRNA, protein and enzyme activity are often
      discordant depending on the stress, its duration and repetition of exposure. The
      extremes are concordant changes in mRNA and protein/activity vs. highly elevated
      mRNA with no change in protein/activity. Post-transcriptional and/or post
      translational regulatory influences that may contribute to the complex effects of
      stress on TH, PNMT and the stress hormone epinephrine are explored.

PMID- 17514581
TI  - Effect of peripherally administered lipopolysaccharide (LPS) on GTP
      cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus
      in mice.
AB  - Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram
      negative bacteria, triggers cells to synthesize and release inflammatory
      cytokines that may progress to septic shock in vivo. We found that LPS enhances
      tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP
      cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115.
      Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC)
      in mice was enhanced by peripheral administration of LPS, resulting in increased
      concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3
      methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH)
      activity is increased by increased content of BH4 due to enhanced mRNA expression
      of GCH in the LC resulting in the increase in norepinephrine in the LC during
      endotoxemia. LPS in blood may act as a stressor to increase norepinephrine
      biosynthesis in the mouse LC.

PMID- 17514582
TI  - Influence of prior experience with homotypic or heterotypic stressor on stress
      reactivity in catecholaminergic systems.
AB  - Here we review how prior experience with stress alters the response to a
      subsequent homotypic or heterotypic stressor, focusing on the catecholaminergic
      systems in the adrenal medulla and the locus coeruleus (LC). The changes in
      response to homotypic stress differ depending on the stressor applied. With
      immobilization stress (IMO), transcriptional responses in the adrenal medulla to
      a single exposure are pronounced and several of the transcription factors and
      signaling kinases induced or activated are reviewed and compared to the longer
      term alterations with repeated stress, consistent with persistent activation of
      gene expression of catecholamine (CA) biosynthetic enzymes. In the LC,
      transcriptional and post-transcriptional activation of gene expression are shown
      to be important. Repeated IMO stress triggers further activation of a number of
      signalling pathways. Neither adrenal medulla nor LC display habituation to long
      term repeated stress. In contrast, gene expression for CA biosynthetic enzymes
      habituates to prolonged cold stress in the adrenal medulla and LC, but displays
      an exaggerated response with exposure to a novel or heterotypic stressor such as
      IMO. Some of the transcriptional pathways displaying sensitization are described.

PMID- 17514583
TI  - Cross over of forebrain and brainstem neuronal projections to spinal cord
      sympathetic preganglionic neurons in the rat.
AB  - Neuronal inputs from the forebrain and the brainstem to sympathetic preganglionic
      neurons in the spinal cord were investigated by the transneuronal retrograde
      tracing technique using pseudorabies virus in intact and brainstem-lesioned rats.
      After unilateral subcutaneous viral inoculations into the hind limb of intact
      rats, infected neurons were then visualized by immunostaining. At 3.5 days after
      inoculation, infected neurons appeared in the thoracic (T10) intermediolateral
      (IML) cell column. On the 4th day, infected neurons were present in the C1, A5,
      A6, A7 catecholamine cell groups and the rostral ventromedial medulla (RVMM). On
      the 5th day, viral labeling was seen in the hypothalamic paraventricular and
      arcuate nuclei and the lateral hypothalamic area. In all of these nuclei, the
      infected cells appeared bilaterally. However, the appearance of virus-labeled
      cells in these nuclei was unilateral following unilateral coronal sections
      between the medulla and the spinal cord (depending on the side of hemisection,
      but not on the site of virus inoculation). Midsagittal sections throughout the
      entire medulla oblongata did not alter the topographical pattern of virus
      infected neurons in the forebrain or the brainstem. These findings indicate that
      descending fibers to the spinal neurons may not cross over in the lower brainstem
      but that they decussate within the spinal cord.

PMID- 17514584
TI  - Negative regulation of corticotropin releasing factor expression and limitation
      of stress response.
AB  - Corticotropin releasing factor (CRF) coordinates behavioral, autonomic and
      hormonal responses to stress. Activation of the hypothalamic pituitary adrenal
      (HPA) axis with stimulation of CRF and vasopressin (VP) release from hypothalamic
      parvocellular neurons, and consequent secretion of ACTH from the anterior
      pituitary and glucocorticoid from the adrenal cortex, is the major endocrine
      response to stress. Current evidence indicates that the main regulator of ACTH
      secretion in acute and chronic conditions is CRF, in spite of the fact that the
      selective increases in expression of parvocellular VP and pituitary VP V1b
      receptors observed during prolonged activation of the HPA axis have suggested
      that VP becomes the predominant regulator. Following CRF release, activation of
      CRF transcription is required to restore mRNA and peptide levels, but termination
      of the response is essential to prevent pathology associated with chronic
      elevation of CRF and glucocorticoid production. While glucocorticoid feedback
      plays an important role in regulating CRF expression, the relative importance of
      direct transcriptional repression of the CRF gene by glucocorticoids in the
      overall feedback mechanism is not clear. In addition to glucocorticoids,
      intracellular feedback mechanisms in the CRF neuron, involving induction of
      repressor forms of cAMP response element modulator (CREM) limit CRF
      transcriptional responses by competing with the positive regulator, phospho-CREB.
      Rapid repression of CRF transcription following stress-induced activation is
      likely to contribute to limiting the stress response and to preventing disorders
      associated with excessive CRF production.

PMID- 17514586
TI  - Adrenergic and calcium modulation of the heart in stress: from molecular biology
      to function.
AB  - There is strong evidence about the importance of catecholamines and calcium
      signaling in heart function. Also, interaction of these two systems is well
      documented. Catecholamines signal through adrenergic receptors, and further
      activate calcium transport either from the extracellular space, or from the
      intracellular calcium stores. This review summarizes current knowledge on
      catecholamine production in the heart, with special focus on the final enzyme in
      the catecholamine synthesizing pathway, phenylethanolamine N-methyltransferase
      (PNMT), in different cell types in the heart. Further, signaling through
      different types of adrenergic receptors in physiological conditions and after
      exposure to different stressors is discussed. Also, part of this review considers
      activation of an intracellular calcium transport system via inositol 1,4,5
      trisphosphate receptor and to possible functional consequences in control and
      stress conditions.

PMID- 17514585
TI  - Differing effects of acute and chronic stressors on plasma osteocalcin and leptin
      in rats.
AB  - Stressor activation of the sympathetic nervous system and the hypothalamic
      pituitary-adrenal axis can have profound effects on bone and also appetite and
      metabolism. We tested in rats the response of plasma osteocalcin (pOC, a bone
      biomarker that is acutely stress responsive), corticosterone, and leptin to (1)
      ethanol consumption (5% w/v) in a liquid diet (compared with ad libitum and pair
      fed rats), (2) acute restraint, and (3) acute (once, 1 h) and (4) chronic (1
      h/day for 7 weeks) social aggression. Basal pOC concentration did not differ with
      ethanol diet or social interaction, but was elevated by both foot restraint
      immobilization (Imo) and restraint in wire mesh cylinders (WMR). As previously
      reported for chronic Imo, ingestion of ethanol blunted the pOC response to Imo.
      Plasma corticosterone concentration was increased by acute WMR and acute social
      interaction but was unaltered by chronic social interaction. Plasma leptin
      concentration was markedly increased by Imo in ad libitum fed, but only slightly
      in ethanol or pair-fed rats. In contrast, the data reflect significant
      differences between acute and chronic stressor effects since chronic social
      stress had little effect on pOC or plasma corticosterone, but tended to decrease
      leptin level in relation to dominance. Lack of significant impact of prolonged
      ethanol intake or social aggression suggests physiological adaptation.

PMID- 17514587
TI  - Brain and peripheral angiotensin II play a major role in stress.
AB  - Angiotensin II (Ang II), the active principle of the renin-angiotensin system
      (RAS), was discovered as a vasoconstrictive, fluid retentive circulating hormone.
      It was revealed later that there are local RAS in many organs, including the
      brain. The physiological receptor for Ang II, the AT(1) receptor type, was found
      to be highly expressed in many tissues and brain areas involved in the
      hypothalamic-pituitary-adrenal axis response to stress and in the sympathoadrenal
      system. The production of circulating and local Ang II, and the expression of
      AT(1) receptors increase during stress. Blockade of peripheral and brain AT(1)
      receptors with receptor antagonists administered peripherally prevented the
      hormonal and sympathoadrenal response to isolation stress, the stress-related
      alterations in cortical CRF(1) and benzodiazepine receptors, part of the GABA(A)
      complex, and reduced anxiety in rodents. AT(1) receptor blockade prevented the
      ulcerations of the gastric mucosa produced by cold-restraint stress, by
      preservation of the gastric blood flow, prevention of the stress-induced
      inflammatory response of the gastric mucosa, and partial blockade of the
      sympathoadrenal response to the stress. Our observations demonstrate that Ang II
      is an important stress hormone, and that blockade of AT(1) receptors could be
      proposed as a potentially useful therapy for stress-induced disorders.

PMID- 17514588
TI  - Pheochromocytoma as a catecholamine producing tumor: implications for clinical
      practice.
AB  - Pheochromocytomas are catecholamine-producing tumors presenting with various
      clinical symptoms, but mostly with headache, sweating, palpitations and
      hypertension. If not properly diagnosed, secretion of catecholamines may lead to
      fatal cardiovascular consequences. Biochemical testing for pheochromocytoma
      should be performed not only in symptomatic subjects or in subjects with adrenal
      incidentaloma but also in subjects with a genetic predisposition for
      pheochromocytoma (multiple endocrine neoplasia type 2, Von Hippel-Lindau (VHL)
      syndrome, neurofibromatosis type 1 (NF 1)and mutations of succinate dehydrogenase
      (SDH) genes). Once a pheochromocytoma is proven, computed tomography (CT),
      magnetic resonance imaging (MRI) and functional imaging with [(123)I]-MIBG may be
      used for tumor localization. Adequate medical pre-treatment is essential for
      successful operation which is performed in most cases by laparoscopy. After tumor
      removal, further follow-up is necessary due to possible recurrence. Although
      prognosis after tumor resection is excellent, a significant proportion of
      pheochromocytomas recur, some as metastases. Thus, appropriate follow-up is
      mandatory.

PMID- 17514589
TI  - Growth hormone response to different consecutive stress stimuli in healthy men:
      is there any difference?
AB  - The contribution of growth hormone (GH), released during acute and repeated
      stressful situations, to the development of stress-related disorders is often
      neglected. We have hypothesized that the modulation of the GH response to
      sequential stress exposure in humans depends mainly on the nature of the
      stressor. To test this hypothesis, we compared GH responses to different
      stressful situations, namely aerobic exercise, hypoglycemia and hyperthermia,
      which were applied in two sequential sessions separated by 80-150 min. In
      addition, administration of the dopaminergic drug apomorphine was used as a
      pharmacological stimulus. GH responses to submaximal exercise (bicycle ergometer,
      increasing work loads of 1.5, 2.0 and 2.5 W/kg, total duration 20 min) and
      hyperthermia in a sauna (80 degrees C, 30 min) were prevented when preceded by
      the same stress stimulus. Hypoglycemia induced by insulin (0.1 IU/kg
      intravenously) resulted in a significant GH response also during the second of
      the two consecutive insulin tests, though the response was reduced.
      Administration of apomorphine (0.75 mg subcutaneously) or insulin prevented the
      increase in GH release in response to a sequential bolus of apomorphine, while
      hypoglycemia induced a significant elevation in GH levels even if applied after a
      previous treatment with apomorphine. In conclusion, the feedback inhibition of
      the GH response to a sequential stress stimulus depends on the stimulus used.
      Unlike in the case of exercise and hyperthermia, mechanisms involved in the
      stress response to hypoglycemia appear to overcome the usual feedback mechanisms
      and to re-induce the GH response when applied after another stimulus.

PMID- 17514590
TI  - Glucocorticoid action networks and complex psychiatric and/or somatic disorders.
AB  - Glucocorticoids contribute fundamentally to the maintenance of basal and stress
      related homeostasis in all higher organisms. These hormones influence a large
      percentage of the expressed human genome and their effects spare almost no organs
      or tissues. Glucocorticoids influence many functions of the central nervous
      system, such as arousal, cognition, mood and sleep, the activity and direction of
      intermediary metabolism, the maintenance of a normal cardiovascular tone, the
      activity and quality of the immune and inflammatory reaction, including the
      manifestations of the sickness syndrome, as well as growth and reproduction. The
      numerous actions of glucocorticoids are mediated by a set of at least 16
      glucocorticoid receptor (GR) isoforms forming homo- or hetero-dimers. The GRs
      consist of multifunctional domain proteins operating as ligand-dependent
      transcription factors that interact with many other cell signaling systems. The
      presence of multiple GR monomers and dimers expressed in a cell-specific fashion
      at different quantities with quantitatively and qualitatively different
      transcriptional activities suggests that the glucocorticoid signaling system is
      highly stochastic. Based on ample evidence, we present our conception that
      glucocorticoids are heavily involved in human pathophysiology and influence life
      expectancy. Common psychiatric and/or somatic complex disorders, such as anxiety,
      depression, insomnia, chronic pain and fatigue syndromes, obesity, the metabolic
      syndrome, essential hypertension, diabetes type 2, atherosclerosis with its
      cardiovascular sequelae, and osteoporosis, as well as autoimmune inflammatory and
      allergic disorders, all appear to have a glucocorticoid component.

PMID- 17514591
TI  - Contingency judgements on the fly.
AB  - The present research was conducted to establish the validity of a novel procedure
      for measuring human contingency judgements aimed at shortening the length of
      conventional procedures. Cues and outcomes were simple geometric shapes that were
      presented in a rapid streaming fashion, reducing the length of a block of trials
      from several minutes to a few seconds. We establish the reliability of the
      procedure by replicating two central findings in the contingency judgement
      literature, and we elaborate on the importance of this method for future
      research.

PMID- 17514592
TI  - Cue-task associations in task switching.
AB  - Cognitive flexibility can be studied using the task-switching paradigm. This
      paradigm requires subjects to adapt behaviour to changing contexts as indicated
      by a cue. In our study, we addressed the question of how cue-based implementation
      of mental "task sets" occurs. We assumed that cues build up associations to the
      tasks that they indicate. These associations lead to retrieval of the associated
      task set once the cue shows up again. In three experiments, we tested this
      assumption using a negative transfer paradigm. First participants were exposed to
      one cue-task mapping. After a training phase, the cue-task mapping changed in
      either of two ways. Whereas one group of participants got new cues, the other
      experienced a reversal of the learnt cue-task mapping. Our results show that
      participants build up cue-task associations and that these formerly learnt
      associations can hamper the implementation of new cue-task mappings (particular
      with mapping reversal). Prolonged preparation time decreased the cost of changing
      the cue-task mapping but did not change the overall pattern of results.

PMID- 17514593
TI  - The transfer of movement sequences: effects of decreased and increased load.
AB  - A number of recent experiments have demonstrated that a movement structure
      develops during the course of learning a movement sequence that provides the
      basis for transfer. After learning a movement sequence participants have been
      shown to be able to effectively produce the sequence when movement demands
      require that the sequence be rescaled in amplitude or produced with an
      unpractised set of effectors. The purpose of the present experiment was to
      determine whether participants, after learning a complex 16-element movement
      sequence with a 0.567-kg load, could also effectively produce the sequence when
      the load was decreased (0.0 kg) or increased (1.134 kg). The results indicated
      that participants were able to effectively compensate for decreased and increased
      load with virtually no changes in performance characteristics (displacement,
      velocity, acceleration, and pattern of element durations) while electromyographic
      (EMG) signals demonstrated that smaller (reduced load) or larger forces
      (increased load) were spontaneously generated to compensate for the change in
      load. The muscle activation patterns of the biceps and triceps as well as the
      level of coactivation appeared to be generally upscaled to generate and dissipate
      the changes in force requirement needed to compensate for the increased load.

PMID- 17514594
TI  - Questions versus statements: challenging an assumption about semantic illusions.
AB  - In previous semantic-illusion research the tacit assumption has been that
      questions and statements-to-be-verified of similar semantic content lead to a
      similar proportion of semantic illusions. This assumption was made despite the
      fact that questions are thought to have different processing demands from those
      of statements. This paper presents empirical evidence that questions tend to lead
      to more semantic illusions than do statements-to-be-verified. Two experiments
      were carried out to provide a direct comparison between the semantic-illusion
      rates for statements and for questions. In Experiment 1, open-ended questions led
      to significantly more semantic illusions than did true/false statements.
      Experiment 2 replicated this effect using multiple-choice response options in the
      question condition. It is concluded that the syntactic form of a sentence affects
      the way in which semantic information is processed, and the implications of the
      findings are discussed.

PMID- 17514595
TI  - Two meanings of "if"? Individual differences in the interpretation of
      conditionals.
AB  - This work investigates the nature of two distinct response patterns in a
      probabilistic truth table evaluation task, in which people estimate the
      probability of a conditional on the basis of frequencies of the truth table
      cases. The conditional-probability pattern reflects an interpretation of
      conditionals as expressing a conditional probability. The conjunctive pattern
      suggests that some people treat conditionals as conjunctions, in line with a
      prediction of the mental-model theory. Experiments 1 and 2 rule out two
      alternative explanations of the conjunctive pattern. It does not arise from
      people believing that at least one case matching the conjunction of antecedent
      and consequent must exist for a conditional to be true, and it does not arise
      from people adding the converse to the given conditional. Experiment 3
      establishes that people's response patterns in the probabilistic truth table task
      are very consistent across different conditionals, and that the two response
      patterns generalize to conditionals with negated antecedents and consequents.
      Individual differences in rating the probability of a conditional were loosely
      correlated with corresponding response patterns in a classical truth table
      evaluation task, but there was little association with people's evaluation of
      deductive inferences from conditionals as premises. A theoretical framework is
      proposed that integrates elements from the conditional-probability view with the
      theory of mental models.

PMID- 17514596
TI  - Testing the representation of time in reference memory in the bisection and the
      generalization task: the utility of a developmental approach.
AB  - This study examined the effect of the variability of representation of durations
      in reference memory on temporal discrimination performance in children aged 5 and
      8 years as well as in adults using a bisection (Experiment 1) and a
      generalization task (Experiment 2). In each task, the participants were
      familiarized before the blocks of tested trials with either the same referent
      duration values (fixed condition) or a distribution of referent duration values,
      with a mean equal to the referent durations used in the fixed condition and a .20
      coefficient of variation (variable condition). The results showed that the
      sensitivity to duration was lower in the variable than in the fixed condition in
      the children and, to a lesser extent, in the adults. The modelling of the data
      indicated that this effect was due to the increase in the variability of the
      representation of durations in reference memory, but also to changes in the
      decisional processes.

PMID- 17514597
TI  - Mechanisms of the associated nontargets effect: processes influenced by
      statistical learning in a simple visual environment.
AB  - In three visual search experiments participants were asked to make a target
      response if either of two targets was present and to make a nontarget response if
      neither target was present. Some target-absent displays included only nontarget
      features that never occurred in the same displays as target features, whereas
      other target-absent displays included nontarget features that did sometimes occur
      with target features. Nontarget responses were reliably faster in the former case
      than in the latter. This "associated nontargets effect" appears to arise from
      participants' ability to learn and to use contingencies between the presence of
      certain nontargets and the absence of any target.

PMID- 17514598
TI  - Localizing practice effects in dual-task performance.
AB  - Practice effects on dual-task processing are of interest in current research
      because they may reveal the scope and limits of parallel task processing. Here we
      used onsets of the lateralized readiness potential (LRP), a time marker for the
      termination of response selection, to assess processing changes after five
      consecutive dual-task sessions with three stimulus onset asynchronies (SOAs) and
      priority on Task 1. Practice reduced reaction times in both tasks and the
      interference between tasks. As indicated by the LRP, the reduction of dual-task
      costs can be explained most parsimoniously by a shortening of the temporal
      demands of central bottleneck stages, without assuming parallel processing.
      However, the LRP also revealed a hitherto unreported early activation over the
      parietal scalp after practice in the short SOA condition, possibly indicating the
      isolation of stimulus-response translation from other central processing stages.
      In addition, further evidence was obtained from the LRP for a late motoric
      bottleneck, which is robust against practice.

PMID- 17514599
TI  - Transfer of learning in avoiding false memory: the roles of warning, immediate
      feedback, and incentive.
AB  - Participants learned semantic associates and were tested in the Deese-Roediger
      McDermott (DRM) paradigm. A multiple-trial learning procedure with warning,
      feedback, and monetary incentive was employed to reduce false memory. Results
      showed that there was a progressive reduction of false memory over the trials as
      well as a generalization of learning to new lists of words in avoiding the
      critical nonpresented words attributable to explicit warning, feedback, and
      incentive, respectively. Both the feedback and the monetary incentive had an
      effect beyond what an explicit warning could obtain. In addition, participants
      were found to achieve false-memory reduction by enhancing the activation of the
      critical words and the monitoring process, rather than by strengthening the
      verbatim processing of the list words. It was concluded that false memory may not
      be as impervious to correction as was believed insofar as an effective training
      method is applied.

PMID- 17514600
TI  - Predicting placental abruption and previa in women with a previous cesarean
      delivery.
AB  - The purpose of this study was to determine if placental abruption or previa in
      women with a history of a prior cesarean delivery (CD) can be predicted. A
      retrospective cohort study of pregnant women with previous CD was conducted in 17
      centers between 1996 and 2000. Women developing placenta previa or abruption in
      the subsequent pregnancy were compared with those without these complications.
      Bivariate and multivariable techniques were used to develop predictive models for
      placenta previa or abruption. The area under the receiver-operator characteristic
      curves, sensitivity, specificity, and accuracy of the models were compared. Among
      25,076 women with prior CD, there were 361 (15 per 1000 births) with placenta
      previa and 309 (13 per 1000 births) with abruption. The significant risk factors
      for these complications include advanced maternal age, Asian race, increased
      parity, illicit drug use, history of spontaneous abortion, and three or more
      prior cesarean deliveries. Prediction models for abruption and previa had poor
      sensitivity (12% and 13% for abruption and previa, respectively). In women with
      at least one prior cesarean delivery, the risk factors for placental previa and
      abruption can be identified. However, prediction models combining these risk
      factors were too inefficient to be useful.

PMID- 17514601
TI  - Maternal obesity: can pregnancy weight gain modify risk of selected adverse
      pregnancy outcomes?
AB  - Reports by the Institute of Medicine (IOM) recommend that gestational weight gain
      goals should be modified according to prepregnancy body mass index (BMI), which
      could result in better maternal and infant outcomes. The authors assessed whether
      the risk of the pregnancy outcomes such as rate of cesarean section to
      primiparous and multiparous women, macrosomia, and breastfeeding at 10 weeks
      postpartum can be modified by following the IOM guidelines for gestational weight
      gain irrespective of prepregnancy BMI. Staff from the New Jersey Pregnancy Risk
      Assessment Monitoring System interviewed a sample of women who delivered live
      births in New Jersey during 2002 through 2005 (n = 7661). In New Jersey, 18% of
      mothers were obese, 13% were overweight, and 16% were underweight. In logistic
      regression analyses, after controlling for maternal characteristics, the effect
      of prepregnancy obesity and weight gain more than 34 lb independently and
      significantly increased the risk of all four adverse outcomes. For no outcomes
      was the 25- to 34-pound weight gain category significantly distinguishable from
      the 16- to 24-pound reference category. These results strongly support the idea
      that the IOM weight gain recommendation (education during preconception regarding
      the importance of optimal BMI at the start of pregnancy) will help to achieve
      better pregnancy outcomes in obese and overweight women.

PMID- 17514602
TI  - Serum lipid peroxidation and antioxidant potential levels in hyperemesis
      gravidarum.
AB  - Hyperemesis gravidarum (HEG) is a severe form of nausea and vomiting with unknown
      etiology. Recent studies have suggested that there might be an etiologic role for
      HELICOBACTER PYLORI (HP) in HEG. HP is a Gram-negative bacterium that colonizes
      the gastric mucosa, increases the generation of reactive oxygen species (ROS),
      and decreases plasma antioxidants such as ascorbic acid. The aim of this study
      was to investigate plasma ROS activities and antioxidant status, and their
      relationship with HP infection, in HEG womens. Twenty-five HEG women, 20
      gestational age- and gravida-matched healthy pregnant controls, and 15
      nonpregnant women were examined for specific immunoglobulin G (IgG) against HP,
      serum malondialdehyde (MDA) as a measure of lipid peroxidation, and activity of
      antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px),
      and catalase (CT). Compared with controls, the seropositivity of HP for IgG was
      significantly higher ( P < 0.01) in pregnancies with HEG. When three study groups
      (including both HP + and HP- patients) were compared with each other with respect
      to the study parameters, MDA concentration increased significantly in pregnant
      women when compared with control group (nonpregnant women; P < 0.01), as well as
      in HEG compared with healthy pregnant women ( P < 0.01). The SOD, GSH-Px, and CT
      activity were increased in the group of normal pregnant women versus the
      nonpregnant group ( P < 0.01), but decreased significantly in the group of HEG
      pregnant women ( P < 0.01). Serum MDA levels and SOD, GSH-Px, and CT activity
      were not affected by the seropositivity of HP for IgG in either group ( P >
      0.05). The results of the present study suggest that HEG is an oxidative stress
      condition, as reflected by the increased ROS activity and decreased antioxidant
      status, regardless of HP infection.

PMID- 17514603
TI  - Chimerism: a new look.
AB  - INTRODUCTION: Microchimerism has become a familiar term in the past few years.
      Many groups all over the globe, specializing in a diverse array of basic and
      medical sciences, have turned their attention to microchimerism, its possible
      role in disease or repair, and its mechanism of action in the host body. We
      reviewed the current knowledge about this novel term. MATERIALS AND METHODS: We
      search the PubMed, using all the derivatives of chimera. All papers and their
      bibliographic information published by December 2005 were reviewed and 61 were
      selected. RESULTS: Microchimerism is the presence of foreign or nonhost cells in
      a body. These are cells that live, differentiate, and persist in the host body by
      definition. These cells can enter the host body in a variety of manners. The most
      familiar aspect is microchimerism resulting from organ transplant. For many years
      now scientists have been debating over the interpretation of this phenomenon. We
      know that donor cell engraftment in the recipient body is a sign of
      transplantation success. What this means is that the body has developed tolerance
      toward the foreign organ and created a chimer. CONCLUSION: How long this chimeric
      state will last, whether these cells will induce or be induced to create a
      chronic complication in the long run, or will these genetically distinct cell
      types live peacefully in one body to the end of the host's life are the essence
      of the ongoing discussion and what probes researchers to continue their search.

PMID- 17514604
TI  - Correlation between size of renal cell carcinoma and its grade, stage, and
      histological subtype.
AB  - INTRODUCTION: The aim of this study was to determine the correlation between
      histological subtype, size, grade, and stage of the kidney tumors and to
      investigate whether a correlation exists between the size of the kidney tumor and
      its behavior. MATERIALS AND METHODS: Between 1996 and 2004, we had 212 patients
      with radical or partial nephrectomy due to a kidney tumor at Shaheed Labbafinejad
      Medical Center. Their pathologic blocks were re-evaluated with consideration of
      their tumor size and pathologic features. RESULTS: Of 212 pathologic blocks, 17
      (8%) were benign and 195 (92%) were malignant masses including 179 renal cell
      carcinoma (RCC) tumors. Malignant tumors were slightly greater compared with the
      benign ones (P=.10). There was no significant relation between the size of tumor
      and the histological subtype. Significant relations between the size of the
      kidney tumor and the nuclear grade (P=.007), clinical symptoms (P=.02), and
      extracapsular extension (P<.001) were observed. In smaller RCC tumors (< 4 cm),
      extracapsular extension (stages T3 and T4) was rare (1 in 29). However, smaller
      RCC tumors were not significantly different from those larger than 4 cm regarding
      the nuclear grade, symptoms, and histological subtypes. CONCLUSION: Tumor size is
      not an independent predictor for the histological subtype of the tumors; however,
      larger malignant tumors may have higher grades, higher stages, and clinical
      symptoms.

PMID- 17514605
TI  - Pregnancy outcome in kidney transplant patients.
AB  - INTRODUCTION: Advances in surgical techniques and immunosuppressive therapy have
      improved the survival and quality of life in organ transplant patients. Thus, the
      number of organ transplant women at their reproductive age has also increased. We
      sought to investigate the allograft and obstetric outcomes in pregnant kidney
      recipients. MATERIALS AND METHODS: Seventy-four kidney recipient women with 95
      conceptions during their posttransplant period were evaluated. Pregnancy outcome,
      kidney allograft function, and maternal, fetal, and neonatal complications were
      evaluated in these patients. RESULTS: The mean interval between kidney
      transplantation and pregnancy was 41.0 +/- 9.5 months. Twenty-three pregnancies
      (24.2%) were unsuccessful due to abortion and stillbirth. The mean birth weight
      was 2385.0 +/- 161.7 g and 45 newborns (62.5%) had a birth weight less than 2500
      g (low birth weight). The mean Apgar score of the live babies was 7.9 +/- 0.7.
      Forty-four (61.1%) babies were admitted to neonatal intensive care unit and early
      neonatal death happened in 4 (5.5%). Fifteen mothers (15.78%) had an uneventful
      perinatal period. The most common maternal complications in the 95 pregnancies
      were anemia in 62 (65.3%) and preeclampsia in 45 (47.4%). Three patients 3 (3.2%)
      lost their graft and 6 (6.3%) had impaired kidney allograft function 2 years
      after pregnancy. CONCLUSION: Pregnant kidney allograft recipients should be
      considered as high-risk patients needing special care under the supervision of a
      team of obstetricians and nephrologists.

PMID- 17514606
TI  - Intravesical Bacillus Calmette-Guerin for treatment of refractory interstitial
      cystitis.
AB  - INTRODUCTION: The aim of this study was to examine the efficacy and safety of
      intravesical Bacillus Calmette-Guerin (BCG) in the treatment of refractory
      interstitial cystitis (IC). MATERIALS AND METHODS: Thirteen patients with
      refractory IC were enrolled in the study. They were scheduled to receive 6 weekly
      courses of treatment with intravesical BCG. Variables including the frequency,
      nocturia, urgency, pelvic pain, dyspareunia, dysuria, IC symptom index, IC
      problem index, and average voided volume were assessed every 6 months after the
      BCG therapy. RESULTS: Thirteen patients received the complete course of
      intravesical BCG therapy. Twenty-four months after the treatment a mean
      improvement of 51.9% was seen in frequency (P=.001), 43.2% in nocturia (P=.002),
      28.7% in urgency (P=.004), 43.1% in pelvic pain (P=.001), 58.3% in dyspareunia
      (P=.003), 6.5% in dysuria (P=.16), 57.7% in the O'Leary-Sant IC symptom index
      (P=.001), and 61.8% in the O'Leary-Sant IC problem index (P=.001) scores. A
      significant improvement was seen in the mean average voided volume at the 24th
      follow-up month (89.5%; P=.001). CONCLUSION: Intravesical BCG is a relatively
      effective treatment in patients with refractory IC. Its efficacy seems to be
      modest and lasts for at least 24 months in majority of the patients. It is also
      safe and well tolerated.

PMID- 17514607
TI  - Asymptomatic bacteriuria in pregnant women.
AB  - INTRODUCTION: The aim of this study was to evaluate the frequency of bacteriuria
      in pregnant women referred to the medical centers of Tabriz, Iran, for prenatal
      care. MATERIALS AND METHODS: A total of 1100 healthy pregnant women who were
      referred to 50 medical centers in Tabriz for a regular prenatal care were
      evaluated for bacteriuria. RESULTS: The frequency of asymptomatic bacteriuria was
      6.1%. Maternal age was lower in the women with a positive urine culture (P=.02).
      Asymptomatic bacteriuria had no relationship with gestational age, parity, level
      of education, and body mass index. CONCLUSION: We found a relatively high rate of
      bacteriuria in our cohort of asymptomatic pregnant subjects, especially the
      younger ones. For prevention from the complications of the asymptomatic
      bacteriuria in pregnant women, such as pyelonephritis, hypertension,
      preeclampsia, low birth weight, prematurity, septicemia, and even maternal and
      neonatal death, it is recommended to perform urine culture as a routine
      evaluation during the pregnancy.

PMID- 17514608
TI  - Erectile dysfunction in men with angiographically documented coronary artery
      disease.
AB  - INTRODUCTION: We evaluated erectile function of men with coronary artery disease
      (CAD) and the relation between the degree of erectile dysfunction (ED) and the
      extent of coronary artery stenosis on cardiac angiography. MATERIALS AND METHODS:
      Nondiabetic men with CAD documented by angiography were evaluated for ED.
      Erectile function was assessed by a 5-item version of the International Index of
      Erectile Dysfunction, the Sexual Health Inventory for Men (SHIM). RESULTS: Of 401
      men, 186 (46.4%) had ED (SHIM score, 21 or less). Men with ED were more likely to
      have more than 1 stenotic cardiac vessel (P<.001). The mean SHIM score was 20.9
      +/- 7.6, 12.9 +/- 9.2, and 14.3 +/- 9.1 for men with 1-, 2-, and 3-vessel
      disease, respectively (P<.001). Multivariate analysis showed that only the SHIM
      score had a relationship with the number of involved vessels (P<.001); the SHIM
      score was lower and ED was more frequent in men with more than 1 vessel
      involvement. Forty-one patients (19.1%) without ED and 45 (24.2%) with ED had a
      positive history of myocardial infarction (P=.21). Symptoms of ED had appeared
      prior to CAD detection in 78 out of 189 patients (41.9%) with a mean time
      interval of about 23 months (range, 10 to 36 months). CONCLUSION: Our finding
      showed that the prevalence of ED is relatively high in patients with CAD, and has
      a relationship with the extent of CAD. Furthermore, ED may occur before CAD with
      an average interval of 2 years.

PMID- 17514609
TI  - Varicocele in brothers of patients with varicocele.
AB  - INTRODUCTION: The aim of this study was to evaluate varicocele patients' brothers
      to determine whether they are at a higher risk of varicocele than the general
      population of men. MATERIALS AND METHODS: A total of 56 patients with varicocele
      and their 131 brothers (> 16 years old) were evaluated. The brothers had no
      complaints of infertility, pain, or cosmetic problems. They were all examined for
      varicocele. One hundred and fifty men who referred for employment medical
      examinations were considered as the control group. RESULTS: Of the subjects, 39
      (69.6%) had grade III varicocele. Sixty (45.8%) of the brothers had varicocele.
      The grade of varicocele was III in 16 (26.7%) brothers. In the control group,
      varicocele was present in 15 (10%) which was grade III in 5 (33.3%). The
      frequency of varicocele was 4.5-fold greater in the brothers of the patients than
      the controls (P<.001). Also, the frequency of grade III varicocele was
      significantly more than grades I and II in the patients in comparison with their
      brothers and controls with varicocele (P<.001). There was no significant
      difference in the grades between the controls and the patients' brothers (P=.31).
      The frequency of bilateral varicocele was not statistically different between the
      three groups (P=.14). CONCLUSION: Our findings showed that a significant increase
      is seen in the prevalence of varicocele in the patients' brothers compared to men
      in the general population, warranting evaluation of the first-degree relatives of
      men who present with varicocele.

PMID- 17514610
TI  - Diuresis renography for differentiation of upper urinary tract dilatation from
      obstruction: F+20 and F-15 methods.
AB  - INTRODUCTION: The aim of this study was to evaluate diuresis renography with an
      intravenous injection of furosemide 20 minutes after administering the
      radiopharmaceutical (F+20 protocol) or 15 minutes before (F-15 protocol) in
      patients with upper urinary tract dilatation. MATERIALS AND METHODS: Twenty-one
      patients with pyelocaliceal system dilatation, but not ureteral dilatation, on
      ultrasonography were evaluated. The patients underwent diuresis renography using
      the F+20 and F-15 protocols. Renal scan findings and kidney split function were
      recorded. Then, the patients underwent surgical or conservative treatment
      according to their clinical conditions and imaging results. Follow-up was done 3
      and 6 months postoperatively by physical examination, intravenous urography, and
      diuresis renography. RESULTS: Eleven patients (52.4%) had complete obstruction in
      both protocols of renography, and 5 (23.8%) had an equivocal result in the F+20
      and an obstructive pattern in the F-15. These patients underwent surgical
      operation. In 3 patients (14.3%), both protocols demonstrated a normal urinary
      tract. In 2 patients (9.5%), a nonobstructive response in the F+20 and an
      equivocal result in the F-15 were seen. One of them underwent surgical operation
      because of impaired kidney function during the follow-up and 1 was treated
      conservatively. Overall, obstruction was found in 16 out of 21 patients (76.2%)
      by the F-15 protocol, while it was found in 11 (52.4%) by the F+20 protocol
      (P=.01). The mean kidney split function was 55.15% +/- 7.82% and 54.81% +/- 6.87%
      in F+20 and F-15 protocols, respectively (P=.45). CONCLUSION: Using the F-15
      protocol may reduce the equivocal results of the F+20 for diuresis renography.

PMID- 17514611
TI  - Hydatid cyst of urinary tract: 11 cases at a single center.
AB  - INTRODUCTION: We retrospectively reviewed clinical records of 11 patients with
      hydatid cyst of the urinary tract admitted to our institution from 1998 to 2005.
      MATERIALS AND METHODS: Hospital and follow-up records of 11 patients with hydatid
      cyst of the urinary tract were reviewed and data on the patients' symptoms and
      signs at presentation, radiological findings, diagnostic tests, pathologic
      findings, and surgical outcomes were reviewed. RESULTS: The chief complaint was
      flank pain in 7 patients (63.6%). Hydaturia was not seen in any of our patients.
      Ten patients had renal involvement and 1 had a retrovesical hydatid cyst.
      Eosinophilia was detected in 2 of 11 patients who were tested. A positive
      indirect hemagglutination test was seen in 4 of 7 patients and a positive Casoni
      test in 1 of 2. Intravenous urography revealed caliceal distortion in 6 patients
      (54.5%), caliectasis in 3 (27.3%), and nonfunctioning kidney in 2 (18.2%).
      Ultrasonography showed a complex cyst in all of the patients. Computed tomography
      demonstrated multivesicular cystic structure in 4 patients (36.4%), complex cyst
      in 4 (36.4%), and a simple cyst in 3 (27.3%). Definite diagnosis was made only
      after surgical operation. We performed nephrectomy in 2 patients (18.2%), partial
      nephrectomy in 2 (18.2%), cystectomy plus marsupialization in 5 (45.4%), and
      retrovesical surgery in 1 (9.1%). One patient refused surgical treatment. There
      was no perioperative major complication. CONCLUSION: Renal hydatidosis is a rare
      entity and the main challenge is preoperative diagnosis. Radiological and
      serologic studies, although indicative, cannot confirm the diagnosis, and only
      pathologic examination after surgical removal can confirm echinococcal infection.

PMID- 17514612
TI  - Malignant tumor in a horseshoe kidney.

PMID- 17514613
TI  - Unusual migration of intrauterine device into bladder and calculus formation.

PMID- 17514614
TI  - Plexiform neurofibroma of penis.

PMID- 17514615
TI  - Surrogate end points in clinical trials: the case of anti-neutrophil cytoplasm
      antibody-associated vasculitis.

PMID- 17514616
TI  - Novel insights into the regulation of systemic phosphate homeostasis and renal
      phosphate excretion.

PMID- 17514617
TI  - Focus on hypertension.

PMID- 17514618
TI  - Clinical epidemiology of arteriovenous fistula in 2007.
AB  - The native arteriovenous fistula (AVF) is considered the best access for
      hemodialysis due to its longer survival and lower complication rates as compared
      with other forms of vascular access. However, broad practice variation exists in
      the use of AVF among different countries and even within the same country among
      different regions and centers. Several barriers to AVF placement have been
      identified in the last decade that might explain its suboptimal use among both
      prevalent and incident patients. The present review summarizes and discusses
      recent findings from epidemiological studies on practice patterns and risk
      factors for AVF failure. Special emphasis is devoted to drawbacks and payoffs
      consequent upon the choice of the AVF as access for dialysis. In fact the AVF
      requires major investments in the short run but far less assistance and rework
      thereafter. Primary AVF failure, due to early failure or lack of maturation, is
      currently considered a key area of investigation to improve vascular access
      outcomes. The main challenge for the nephrologist today is to minimize the risk
      of primary failure while attempting to provide most patients with a native AVF.
      Improving vascular access outcomes is clearly a complex and difficult task.
      Recent experience from the United States suggests that multidisciplinary
      management is the most appropriate approach to deal with all the multifaceted
      aspects of end-stage renal disease care and to increase the likelihood of
      success.

PMID- 17514619
TI  - Biology of arteriovenous fistula failure.
AB  - Although arteriovenous (AV) fistulae are the preferred form of dialysis access,
      they continue to have significant problems with both early and late failures.
      Despite the magnitude of the clinical problem, however, there are unfortunately
      no effective therapies for AV fistula failure. We believe that this inability to
      intervene is partly due to a lack of understanding about the pathology and
      pathogenesis of AV fistula failure. Therefore, in the current review we will
      initially explore novel concepts about the pathology and pathogenesis of AV
      fistula failure. This information will then be used to suggest potential
      therapeutic interventions for this important, yet unmet clinical need. Finally,
      we will end with a brief description of some state-of-the-art clinical trials
      that are attempting to apply some of these novel therapeutic concepts to the
      recalcitrant clinical problem of AV fistula failure.

PMID- 17514620
TI  - Phosphatemia is related to chromosomal aberrations of parathyroid glands in
      patients with hyperparathyroidism.
AB  - BACKGROUND AND AIMS: It has been well documented that gene and DNA alterations
      occur frequently in benign primary parathyroid adenomas as well as in parathyroid
      glands with secondary hyperplasia. However, it has not been shown whether a
      correlation exists between somatic DNA aberrations and clinical data. METHODS: We
      analyzed the frequency of chromosomal aberrations in adenomas obtained from 25
      patients with primary hyperparathyroidism (pHPT) and 60 parathyroid nodules from
      20 uremic patients with secondary hyperparathyroidism (sHPT). The relation of
      chromosomal aberrations to parathyroid hormone, as well as calcium and phosphate
      serum concentrations, was assessed. Allelic changes were evaluated by
      microsatellite allelotyping using 105 polymorphic markers. RESULTS: Somatic
      chromosomal aberrations were found in 23 out of 25 adenomas, in hyperplastic
      lesions from 16 out of 20 patients. In pHPT as well as in sHPT a positive
      correlation was found between the number of chromosomal alterations and serum
      phosphate concentration (tau=0.270, p=0.05; and tau=0.362, p=0.03, respectively).
      Only in pHPT was a negative correlation of borderline significance between serum
      parathormone (PTH) and number of aberrated chromosomes noticed (tau=-0.258,
      p=0.07). There was no correlation between the number of DNA changes and serum
      concentration of calcium or tumor volume. CONCLUSION: Hyperphosphatemia may
      increase the risk of specific and random chromosomal aberrations due to
      increasing proliferation rate of parathyroid cells in patients with sHPT.

PMID- 17514621
TI  - Simultaneous pancreas-kidney transplant: a single-center long-term outcome.
AB  - BACKGROUND: In patients with type 1 diabetes mellitus and end-stage renal
      disease, simultaneous pancreas-kidney transplantation is associated with
      increased survival when compared with solitary deceased kidney transplant or
      dialysis. We consider that the analysis of our long-term program (based in a
      single center) of simultaneous pancreas-kidney transplantation would provide
      valuable information for this therapeutic approach regarding patient and organ
      survival. METHODS: The outcome of 57 consecutive pancreas-kidney transplants
      patients was analyzed. The analysis included characteristics of the donor and
      recipient and survival rates of patients and both grafts. We also analyzed age
      and modality of renal replacement treatment as possible mortality risk factors.
      RESULTS: Ten-year patient, kidney and pancreas graft survival rates were 75.8%,
      57.2% and 42.7%, respectively. Censoring for patient death, the results for 10
      year kidney and pancreas survival were 78.5% and 58%, respectively. CONCLUSION:
      Our results add evidence to support the notion that the double and simultaneous
      pancreas-kidney transplantation is in fact the treatment of choice in selected
      patients with end-stage renal failure due to type 1 diabetes mellitus.

PMID- 17514622
TI  - TGF-beta1 in chronic allograft nephropathy following renal transplantation.
AB  - BACKGROUND: Evidence from experimental models and clinical studies supports a
      major role for transforming growth factor-beta1 (TGF-beta1) in renal fibrosis.
      The aim of this study was to use repeated measurement of plasma TGF-beta1 as an
      indicator of persistent expression in a cohort of patients during the first 2
      years post-renal transplantation and to correlate the findings with the
      development of chronic allograft nephropathy (CAN). METHODS: Active plasma TGF
      beta1 was quantified in 100 consecutive renal allograft recipients
      (samples/patient = 35.6 +/- 12.9) under standard clinical management for a mean
      of 23 months (range 3.4-45 months). All patients were followed up for a minimum
      of 5 years. RESULTS: By 5 years, 23 patients had developed biopsy-proven CAN
      (CAN+), all of whom had been positive for plasma TGF-beta1. Demographic data were
      compared between patients who were CAN+ and CAN-negative (CAN-) and were not
      significantly different. TGF-beta1 exposure expressed as area under the curve /
      day (AUC/day) was correlated with the incidence of CAN. A Cox regression model
      was used to investigate the interrelationship of CAN, acute cellular rejection
      (ACR) and TGF-beta1 levels. ACR episodes were predictive of the development of
      CAN (log-rank test, p=0.003). After allowing for the effect of ACR (hazard ratio
      [HR]=3.6; 95% confidence ratio [95% CI], 1.5-8.7) between patients with and
      without ACR episodes, p=0.003), the independent effect of TGF-beta1 was confirmed
      (HR=1.7; 95% CI, 1.1-2.6; per quartile; p=0.008). CONCLUSION: The results
      demonstrate that episodes of ACR are highly predictive of chronic damage in the
      graft. Cumulative exposure to TGF-beta1 is identified as an independent predictor
      of CAN in the first 2 years posttransplantation.

PMID- 17514623
TI  - Nerve growth factor (NGF) and NGF-receptor expression in diseased human kidneys.
AB  - BACKGROUND: Nerve growth factor (NGF) has been indicated to be critical to normal
      renal development in rodents. However, little is known about the expression of
      NGF and the high-affinity NGF receptors in human kidneys which is essential for
      promoting the biological and functional activities of NGF. The present study
      examined the presence of NGF, low-affinity (p75) and high-affinity tyrosine
      kinase A (TrkA) NGF receptor (NGFR) immunoreactivity in diseased human kidneys.
      METHODS: Renal biopsies were performed in 24 patients (11 females and 13 males,
      ranging from 12 to 78 years of age), with various renal diseases. Kidney biopsy
      samples were fixed in Bouin fluid for 24 hours, washed, dehydrated, embedded in
      paraplast sections (3-micron thick) and immunostained for NGF, TrkA and p75
      localization. Immunostained sections were evaluated under a Nikon Eclipse E600
      microscope equipped with a x20 objective and a Nikon DMX 1200 digital camera
      connected to a PC computer, with the aid of a computerized image analysis system.
      RESULTS: The results demonstrate the existence of NGF and TrkA in tubular and
      glomerular cells and of p75-positivity in the interstitial and mesangial cells.
      It also shows colocalization of TrkA and NGF, but not TrkA and p75 in tubular and
      glomerular cells, implying that the synthesis and utilization of NGF might be
      autocrinally regulated. CONCLUSIONS: These findings suggest that NGF signaling
      may be important in human kidney and glomerular response to injury, though to
      understand the precise functional significance of these NGF elements in the human
      kidney, further studies need to be done.

PMID- 17514624
TI  - The effect of serum albumin level on iron-induced oxidative stress in chronic
      renal failure patients.
AB  - BACKGROUND: Intravenous iron (IVIR) administration is widely used to treat anemia
      in chronic renal failure (CRF) patients and causes oxidative stress. Despite the
      fact that proteins are extremely susceptible to oxidative stress, there have been
      no studies investigating the relationship between the severity of iron-induced
      acute oxidative stress and serum albumin. Therefore, we wanted to investigate the
      relation between the severity of iron-induced acute oxidative stress and serum
      albumin level in CRF patients. METHODS: A total of 68 patients (22 on
      hemodialysis, 24 on continuous ambulatory peritoneal dialysis and 22 predialytic
      CRF) with absolute iron deficiency were included to the study. Patients with
      acute inflammatory status, serum ferritin level > or = 100 ng/mL, transferrin
      saturation > or = 20%, hemoglobin level > or = 12 g/dL or serum C-reactive
      protein (CRP) level > or = 10 mg/dL were excluded. Serum direct 8
      isoprostoglandin F2 alpha (IsoPG-F2 alpha) level was used as an oxidative stress
      marker. After baseline sampling, 100 mg ferric sucrose was infused within 30
      minutes. Blood samples were drawn to assess changes in oxidative stress marker at
      the end of the IVIR infusion and at 240 minutes. Patients with serum albumin
      level <4 g/dL were defined as hypoalbuminemic and > or = 4 g/dL as
      normoalbuminemic. RESULTS: There were 34 hypoalbuminemic and 34 normoalbuminemic
      patients. Serum IsoPG-F2 alpha level increased in all patients after the
      administration of IVIR. The severity of iron-induced acute oxidative stress was
      more prominent in patients with a low serum albumin level. Serum albumin level,
      presence of diabetes mellitus (DM) and hemoglobin level were found as significant
      predictors of time-dependent changes in serum IsoPG-F2 alpha level. When the
      analyses were repeated in nondiabetic patients, serum albumin level was similarly
      found to be a significant predictor of time-dependent changes in serum IsoPG-F2
      alpha level. CONCLUSION: This study demonstrated a negative interaction between
      iron-induced acute oxidative stress and serum albumin level in CRF patients.
      Because CRF patients with low serum albumin level are at greater risk for iron
      induced acute oxidative stress, new strategies are necessary in this population.

PMID- 17514625
TI  - Urinary albumin excretion associated with arterial wall stiffness rather than
      thickness in type 2 diabetic patients.
AB  - BACKGROUND: A close relationship has been reported between microalbuminuria and
      atherosclerosis in patients with diabetes mellitus. The aim of this study was to
      determine which of the 2 aspects of atherosclerosis, arterial thickening or
      stiffness, has more effect on levels of microalbuminuria in type 2 diabetic
      patients. METHODS: Twenty-four-hour urine samples of 167 Japanese type 2 diabetic
      patients (aged 58 +/- 12 years) without overt proteinuria were collected for
      quantitative analysis of urinary albumin excretion (UAE). Arterial stiffness was
      evaluated by measuring aortic pulse-wave velocity (PWV), and arterial thickness
      was measured by the intima-media thickness (IMT) of the carotid artery. RESULTS:
      The aortic PWV and carotid IMT were both significantly positively correlated with
      logarithmically transformed UAE (r=0.269, p<0.001; and r=0.188, p<0.05,
      respectively). Although there was a significant positive correlation between
      aortic PWV and carotid IMT (r=0.263, p<0.001), multiple regression analyses
      demonstrated that aortic PWV, but not carotid IMT, was a significant factor
      associated with log UAE, independent of other confounding factors (R2=0.246,
      p<0.0001). CONCLUSIONS: These results suggest that increased arterial stiffness,
      but not arterial thickness, is significantly associated with the increase in
      albuminuria, and that decreased arterial distensibility due to increased
      stiffness caused by atherosclerosis may be related to the progression of diabetic
      nephropathy in type 2 diabetic patients.

PMID- 17514626
TI  - Comparison of lipid measures and risk stratification among end-stage renal
      disease patients.
AB  - BACKGROUND: Abnormal lipid profiles are associated with end-stage renal disease
      (ESRD) which significantly contributes to an accelerated progression of coronary
      artery disease. The purpose of this study was to examine the relationships
      between cholesterol measures and differences in risk stratification when using
      National Cholesterol Education Program, Adult Treatment Panel, Third Report (ATP
      III) guidelines, compared with cholesterol particle number and size in ESRD
      patients. METHODS: Lipid profiles were conducted on 541 ESRD patients who were
      chronic hemodialysis patients. Lipid profiles were measured using gel
      electrophoresis and their particle size and concentration measured using nuclear
      magnetic resonance (NMR) spectroscopy. Correlations and risk stratification were
      compared between each lipid measure. RESULTS: The findings suggest that low
      density lipoprotein (LDL) size does not correlate well with LDL cholesterol and
      LDL particle number. The findings also suggest a "disconnect" between traditional
      lipid measures and cholesterol concentration and size when using ATP-III
      guidelines for risk stratification. CONCLUSIONS: The cholesterol risk designation
      variances between risk stratification guidelines and the relationships
      established through Pearson correlations, as illustrated within this patient
      pool, reveal the complex differences between measures of coronary artery disease
      risk. These additional patients considered at-risk using NMR technology may help
      to identify more patients at need for intervention and treatment.

PMID- 17514627
TI  - Cystatin C in heart failure is nothing more than a bystander of glomerular
      filtration.
AB  - BACKGROUND: Cystatin is an ubiquitous protease inhibitor involved in degradation
      of cellular proteins and has recently been associated with increased risk of
      cardiovascular disease and heart failure independent of renal function. We tested
      whether cystatin in heart failure is only associated with renal function or also
      with echocardio-Doppler parameters and factors of myocardial remodeling (C
      reactive protein, endothelin, and natriuretic peptides). METHODS: This was an
      observational study conducted in 100 adult Caucasian outpatients with NYHA class
      I-II heart function without diabetes and ischemic heart, 50 with idiopathic
      dilated cardiomyopathy (DCM) and 50 with uremic cardiomyopathy undergoing
      hemodialysis (HD). Multiple linear regression analysis was performed on cystatin
      concentration using clinical, laboratory (creatinine, high sensitivity C-reactive
      protein, endothelin, B-type natriuretic peptide [BNP]) and echocardio-Doppler
      data as explanatory variables. RESULTS: The heart was more severely involved in
      DCM patients (worse ejection fraction, diastolic volume index, index of
      myocardial performance, left ventricular mass index). Mean values of cystatin,
      creatinine, BNP and C-reactive protein in HD compared with DCM patients were 6,
      9, 5 and 3 times higher, respectively. Mean values of endothelin were comparable
      in both groups. Cystatin significantly correlated with creatinine in both groups
      (r=0.50 in DCM and r=0.37 in HD, and r=0.95 in pooled groups). In the multiple
      regression analysis, only disease group and creatinine within groups were
      significant independent factors that accounted for 94% of the variability of
      cystatin. CONCLUSION: Renal function was the determinant of cystatin in a
      concentration range of 6 times regardless of severity of heart involvement.

PMID- 17514628
TI  - A role for enhanced integrin and FAK expression in uremia-induced parathyroid
      hyperplasia.
AB  - Parathyroid (PT) hyperplasia is a major feature of secondary hyperparathyroidism
      (SH) in uremia. The transforming growth factor-alpha (TGFalpha) / epidermal
      growth factor receptor (EGFR)Ethgrowth loop is the main contributor to uremia
      induced PT hyperplasia. Since integrin beta1 and focal adhesion kinase (FAK) are
      known to directly activate cell growth and enhance EGFR-driven growth, these
      studies examined their contribution to PT hyperplasia in uremia. Western blot
      analysis was used to measure the expression of EGFR, integrin beta1, and the non
      receptor integrin-sensitive FAK, in PT glands from 8 hemodialysis patients with
      various degrees of SH at the time of the surgery, and in a normal human PT gland.
      In all patients, PT EGFR expression was higher than in the normal control.
      Integrin beta1, a direct activator of EGFR-driven growth, was increased in 5 of
      the 8 hyperplastic glands, whereas 7 out of 8 PT glands showed a marked
      enhancement in FAK expression, an elevation unrelated to increases in integrin
      beta1, but directly associated to time in hemodialysis. Similar increases in PT
      FAK content were observed after 1 month after the onset of uremia by 5/6
      nephrectomy in rats. These findings suggest that in kidney disease, the increased
      PT cell growth driven by enhanced EGFR could be further aggravated through
      elevations in integrin beta1 and FAK expression.

PMID- 17514629
TI  - Comparison of pulse and oral steroid in childhood membranoproliferative
      glomerulonephritis.
AB  - BACKGROUND: There has been no controlled study comparing efficacy of pulse versus
      oral steroid therapy in childhood membranoproliferative glomerulonephritis
      (MPGN). This study aimed to compare these therapies and renal outcome over a long
      term period for MPGN. METHODS: Outcome measures in 11 patients with MPGN treated
      with pulse methylprednisolone (MP) were compared with 8 patients with MPGN
      treated with oral prednisolone (P). RESULTS: Nineteen children with idiopathic
      MPGN (mean age 9.75 years, range 3.7-14 years) were followed for a mean period of
      68.21 months (range 4-124 months). Both treatment groups were similar in
      demographic, clinical, laboratory and histopathological characteristics on
      presentation. In the pulse MP group, only 1 patient out of 11 progressed to end
      stage renal failure (ESRF), compared with 4 patients out of 8 in the oral P group
      (p=0.041). For long-term renal survival, those patients with more than 8 years of
      follow-up were further evaluated. Twelve patients had completed 8 years of follow
      up; in the pulse MP group, 1 of 7 patients, compared with 4 of 5 patients in the
      oral P group progressed to ESRF (p=0.039). Chronic damage in the presentation
      biopsy and lack of remission in patients with nephrotic syndrome (NS) were
      positively associated with adverse renal outcome (p=0.02, p=0.006, respectively).
      CONCLUSIONS: Pulse MP therapy may be superior to oral P therapy in children with
      MPGN in preserving renal function without any increase in steroid-related side
      effects. Chronic damage in the presentation biopsy and lack of remission of NS
      are adverse features.

PMID- 17514630
TI  - Recurrent hemolytic uremic syndrome associated with intestinal lymphangiectasia.
AB  - A 17-year-old boy was admitted to the hospital twice in a year for 2 episodes of
      hemolytic uremic syndrome (HUS). During these 2 HUS episodes he had diarrhea,
      decreased serum complement, decreased total protein and decreased serum albumin
      concentrations. We suggest that protein-losing enteropathy and hypocomplementemia
      due to intestinal lymphangiectasia is may be a rare cause of atypical HUS.

PMID- 17514631
TI  - Evaluation of antioxidative properties of Allium species growing wild in Italy.
AB  - The genus Allium (Alliaceae) is an important dietary source of antioxidant
      phytochemical products. The antioxidant activity of some Allium species is well
      known but no information is available on the in vitro antioxidant activities of
      Italian Allium species growing wild. The aim of this study was to examine the in
      vitro antioxidant activity of aqueous extracts of different parts belonging to
      three Allium species growing wild, endemic to Italian flora: Allium neapolitanum
      Cyr., Allium subhirsutum L. and Allium roseum L., compared with the in vitro
      antioxidant activity of aqueous extracts of bulbs and leaves of the greatly
      studied garlic (Allium sativum L.). The antioxidant potential of extracts was
      evaluated using two different spectrophotometric assays: the DPPH test and FRAP
      assay. Furthermore the polyphenolic content was determined in all Allium species.
      The flowers of species growing wild showed the higher antioxidant power.
      Interesting results were shown even by the leaves, while the antioxidant capacity
      of the bulbs was lower. A correlation between the phenolic contents and the
      antioxidant activity was discovered. The differences in antioxidant capacity
      reflect the variability in the Allium species and the parts of the plant used and
      that the bulb of Allium sativum did not show higher antioxidant power.

PMID- 17514632
TI  - Acanthopanax senticosus inhibits nitric oxide production in murine macrophages in
      vitro and in vivo.
AB  - Excess nitric oxide (NO) production has been implicated in inflammatory diseases.
      The present study investigated the inhibitory effect of the stem bark extract of
      Acanthopanax senticosus (A. senticosus) on NO production in murine macrophages in
      vitro and in vivo. In vitro exposure of RAW264.7 cells to 1, 10, 50, 100, 250,
      500 and 1000 microg/mL of A. senticosus extract significantly suppressed NO
      production induced by lipopolysaccharide (LPS) and interferon gamma (IFN-gamma)
      in a dose-dependent manner. In vitro exposure of mouse resident peritoneal
      macrophages to 1, 10, 100 and 1000 microg/mL of A. senticosus extract
      significantly suppressed NO production induced by LPS and IFN-gamma in a dose
      dependent manner. In vivo administration of A. senticosus extract (50, 100 and
      200 mg/kg) to KM mice dose-dependently inhibited LPS and IFN-gamma induced
      production of NO in isolated mouse peritoneal macrophages ex vivo. Exposure to A.
      senticosus extract had no effect on cell viability and systemic toxicity. The
      results demonstrated that the stem bark extract of A. senticosus extract inhibits
      NO production in murine macrophages in vitro and in vivo.

PMID- 17514633
TI  - Analysis of effects of the herbal preparation Circulat on gene expression levels
      in cultured human fibroblasts.
AB  - Circulat is a systemic standardized plant extract formulation that was developed
      for the prevention of severe manifestations of type 2 diabetes such as necrotic
      damage of the plantar foot. With the aim of revealing the molecular mechanisms
      underlying Circulat's biological activity, the effects of Circulat treatment on
      gene expression levels were examined in the cultured human fibroblast cell line
      MRC-5 using Affymetrix oligonucleotide microarrays. The analysis identified 187
      genes, the expression levels of which underwent significant changes upon Circulat
      treatment. These include four genes (IL6, HMGA1, SLC19A2 and C4A) that have been
      implicated previously in the development of diabetes. A large proportion of the
      identified genes are involved in energy metabolism, protein synthesis, glucose
      metabolism and signaling pathways. Synergistic action of the Circulat components
      has also been revealed. Prospective applications of microarray analysis in
      phytopharmacology are discussed.

PMID- 17514634
TI  - Hypochlorous acid scavenging capacity of garlic.
AB  - The ability of the following aqueous garlic extracts to scavenge hypochlorous
      acid (HOCl) was studied: (a) unheated extract of raw garlic (RG), (b) heated
      extract of raw garlic (HRG), (c) extract of boiled garlic cloves (BG) and (d)
      extract of microwave-treated garlic cloves (MG). The HOCl scavenging activity was
      evaluated following changes in the absorption spectrum of catalase (370-450 nm).
      RG, HRG and BG scavenged HOCl in a concentration-dependent way: the IC(50)
      (mg/mL) values for RG, HRG and BG were 0.339 +/- 0.028, 0.632 +/- 0.030 and 0.690
      +/- 0.031, respectively. The HOCl scavenging ability of garlic was significantly
      decreased when garlic cloves or the extract of raw garlic were heated (BG and
      HRG, respectively); this scavenging ability was eliminated when garlic was
      subjected to microwave heating (MG). The IC(50) value for the reference compound,
      ascorbic acid, was 0.500 +/- 0.049 mg/mL. In summary, raw garlic concentration
      dependently scavenged HOCl; this ability was eliminated in extracts of microwave
      treated garlic cloves but not in heated extracts of raw garlic or extracts of
      boiled garlic cloves.

PMID- 17514635
TI  - Differences between women and men in surgical treatment and case fatality rates
      for ruptured aortic abdominal aneurysm in England.
AB  - BACKGROUND: Differences between women and men in treatment and outcome after
      admission with a ruptured abdominal aortic aneurysm (AAA) in England were
      studied. METHODS: Routinely collected data in Hospital Episode Statistics, linked
      to death records, for emergency admissions for ruptured AAA in England were
      analysed. The percentage of patients who underwent surgical repair was
      calculated, together with 30-day case fatality rates and age-adjusted odds ratios
      (ORs), comparing women with men. RESULTS: A total of 2463 women and 7615 men were
      admitted with a primary diagnosis of ruptured AAA (mean age 79.8 and 74.9 years
      respectively); 39.6 per cent of women and 66.4 per cent of men underwent surgical
      repair (OR 0.47 (95 per cent confidence interval 0.42 to 0.52)). Overall, 75.6
      per cent of women and 61.7 per cent of men died within 30 days of admission (OR
      1.36 (1.22 to 1.52)). The death rate for women and men who had surgery was
      similar (OR 1.01 (0.88 to 1.17)); when no operation was performed the mortality
      rate was higher in women, but not significantly so (OR 1.14 (0.91 to 1.42)).
      CONCLUSION: Women with a ruptured AAA were less likely to be treated surgically
      than men, and their overall mortality rate was higher. Lower rates of surgery in
      women than in men may contribute to the higher mortality in women, but other
      explanations are possible.

PMID- 17514636
TI  - Excision biopsy of breast lesions changes the pattern of lymphatic drainage.
AB  - BACKGROUND: The aim was to validate the sentinel node biopsy procedure in women
      who had previous breast excision biopsy by means of determining the
      reproducibility of lymphoscintigraphy after surgery. METHODS: Twenty-five women
      scheduled for excision biopsy of a breast lesion were investigated. The day
      before surgery, (99m)Tc-labelled nanocolloid was injected into the tumour.
      Lymphoscintigraphy was repeated a minimum of 2 weeks after surgery. RESULTS:
      Preoperative lymphoscintigraphy visualized at least one sentinel node in all 25
      women. Discrepancy in the drainage patterns after surgery was noted in 17 of 25
      patients. A change in the drainage pattern in the axilla after excision biopsy
      was seen in 11 women. Drainage to the internal mammary chain was noted before
      surgery in 13 women, but only three had the same drainage pathways after excision
      biopsy. CONCLUSION: After breast excision biopsy lymphoscintigraphy usually
      showed a different drainage pattern. This implies that sentinel node biopsy
      should be performed before excision biopsy to ensure optimal sensitivity.

PMID- 17514637
TI  - Size of surgical margin does not influence recurrence rates after curative liver
      resection for colorectal cancer liver metastases.
AB  - BACKGROUND: The aim of this study was to examine the relationship between
      surgical margin status and site of recurrence after potentially curative liver
      resection for colorectal metastases using an ultrasonic dissection technique.
      METHODS: Between January 2000 and December 2003, 176 patients underwent liver
      resection with curative intent for colorectal metastases at a single institution.
      Demographics, operative data, pathological margin status, site of recurrence and
      long-term survival data were collected prospectively and analysed. RESULTS: On
      pathological analysis, resection margins were positive in 43 patients, negative
      by 1-9 mm in 110, and clear by more than 9 mm in 23 patients. At a median follow
      up of 33 months, 133 of 176 patients had developed a recurrence, only five of
      whom had recurrence at the surgical margin. Recurrence at the surgical margin was
      not significantly related to the size of the margin. Overall, the median time to
      recurrence was 12.6 months, which was independent of surgical margin size,
      although there was a significantly higher proportion of patients with multiple
      metastases in the group with a positive margin (P = 0.008). Margin status did not
      correlate significantly with either recurrence-free or overall survival.
      CONCLUSION: The rate of recurrence at the surgical margin was low and a positive
      margin was not associated with an increased risk of recurrence either at the
      surgical margin or elsewhere.

PMID- 17514638
TI  - Piperonyl butoxide induces the expression of cytochrome P450 and glutathione S
      transferase genes in Drosophila melanogaster.
AB  - Piperonyl butoxide (PBO) is an insecticide synergist known to inhibit the
      activity of cytochrome P450 enzymes. PBO is currently used in some insecticide
      formulations, and has also been suggested as a pretreatment for some pesticide
      applications. Little is known about how insects respond to PBO exposure at the
      gene transcription level. The authors have characterised the transcriptional
      response of the Drosophila melanogaster genome after PBO treatment, using both a
      custom-designed 'detox' microarray, containing cytochrome P450 (P450),
      glutathione S-transferase (GST) and esterase genes, and a full genome microarray.
      A subset of P450 and GST genes is identified, along with additional metabolic
      genes, that are induced by PBO. The gene set is an extremely similar gene set to
      that induced by phenobarbital, a compound for which pretreatment is known to
      confer tolerance to a range of insecticide compounds. The implications of the
      induction of gene families known to metabolise insecticides and the use of PBO in
      pest management programs are discussed.

PMID- 17514639
TI  - Cardiotoxin III induces c-jun N-terminal kinase-dependent apoptosis in HL-60
      human leukaemia cells.
AB  - Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues
      isolated from Naja naja atra venom, has been reported to have anticancer
      activity. The molecular effects of CTX III on HL-60 cells were dissected in the
      present study. We found that the antiproliferative action of CTX III on HL-60
      cells was mediated through apoptosis, as characterized by an increase of sub G1
      population, DNA fragmentation and poly(ADP-ribose) polymerase (PARP) cleavage.
      Upregulation of Bax, downregulation of Bcl-2, the release of mitochondrial
      cytochrome c to cytosol and the activations of capase-9 and -3 were noted, while
      CTX III had no appreciable effect on the levels of Bcl-X(L) and Bad proteins.
      Moreover, c-Jun N-terminal kinase (JNK) was activated shortly after CTX III
      treatment in HL-60 cells. Consistently, the SP600125 compound, an
      anthrapyrazolone inhibitor of JNK, suppressed apoptosis induced by CTX III. As
      expected, this JNK inhibitor also attenuated the modulation of Bax and Bcl-2, as
      well as the cytosolic appearance of cytochrome c and the activation of caspase-3
      and caspase-9 that induced by CTX III. These findings suggest that CTX III can
      induce apoptosis in HL-60 cells via the mitochondrial caspase cascade and the
      activation of JNK is critical for the initiation of the apoptotic death of HL-60
      cells.

PMID- 17514640
TI  - Effects of repeated doses of caffeine on performance and alertness: new data and
      secondary analyses.
AB  - RATIONALE: The effects of caffeine on mood and performance are well established.
      Some authors suggest that caffeine merely reverses effects of caffeine withdrawal
      rather than having direct behavioural effects. It has also been suggested that
      withdrawal may be removed by a first dose of caffeine and further doses have
      little subsequent effect. These issues are examined here. OBJECTIVES: The present
      study aimed to determine whether caffeine withdrawal influenced mood and
      performance by comparing regular consumers who had been withdrawn from caffeine
      overnight with non-consumers. Following this repeated caffeine doses were
      administered to test the claim that repeated dosing has no extra effect on mood
      or performance. Secondary analyses of data collected after a day of normal
      caffeine consumption were also carried out to examine some alternative
      explanations of their results which showed effects of caffeine after a day of
      normal caffeine consumption. METHODS: One hundred and twenty volunteers
      participated in the study. Regular caffeine consumption was assessed by
      questionnaire and this showed that 36 of the volunteers did not regularly consume
      caffeinated beverages. Volunteers were instructed to abstain from caffeine
      overnight and then completed a baseline session measuring mood and a range of
      cognitive functions at 08.00 the next day. Following this volunteers were given
      0, or 1 mg/kg caffeine in a milkshake, glucose solution or water (at 09:00),
      followed by a second 0 or 1 mg/kg caffeine dose (at 09:40) and the test battery
      repeated at 10:00. RESULTS: The baseline data showed no effect of overnight
      caffeine withdrawal on mood or performance. In contrast, caffeine challenge
      improved vigilance performance and prevented decreases in alertness induced by
      completion of the task battery. The magnitude of these effects increased as a
      function of the number of doses of caffeine given. Secondary analyses of data
      from Christopher et al. (2003) also confirmed that effects of caffeine did not
      depend on length of withdrawal. CONCLUSIONS: The present findings show no effect
      of overnight caffeine withdrawal on mood and performance. Caffeine challenge did
      have the predicted effect on alertness and vigilance, with the size of the
      effects increasing with caffeine dose. These findings suggest that the effects of
      caffeine are not due to reversal of effects of withdrawal, a view confirmed by
      secondary analyses of data collected after a day of normal caffeine consumption.

PMID- 17514641
TI  - Faecal incontinence (Br J Surg 2007; 94: 134-144).

PMID- 17514643
TI  - Letter 1: non-patient factors related to rates of ruptured appendicitis (Br J
      Surg 2007; 94: 214-221).

PMID- 17514646
TI  - Global gene expression in Ha-ras and B-raf mutated mouse liver tumors.
AB  - Chemically-induced mouse liver tumors harbor mutations in different oncogenes.
      About 50% of tumors contain activating mutations in the Ha-ras gene contain and
      about 20% of tumors show point mutations in the B-raf oncogene. We have
      investigated the gene expression profiles in tumors of the 2 genotypes by
      microarray analysis. In total, approximately 500 genes or expressed sequences
      were aberrantly expressed in tumors relative to normal liver tissue. Around
      two/thirds of them were significantly altered in both Ha-ras and B-raf mutated
      liver tumors, and most of the remaining genes showed at least qualitatively
      comparable changes in both tumor types. Several functional clusters were
      hypothesized in tumors of the 2 genotypes which involve alterations in a battery
      of genes encoding enzymes of lipid metabolism. The similarity in the patterns of
      global gene expression of Ha-ras and B-raf mutated liver tumors suggests that
      mutational activation of the 2 oncogenes results in activation of a common set of
      transcriptional regulators.

PMID- 17514647
TI  - Gs alpha overexpression and loss of Gs alpha imprinting in human somatotroph
      adenomas: association with tumor size and response to pharmacologic treatment.
AB  - Gs alpha, the alpha-subunit of the heterotrimeric GTP-binding protein, is coded
      from the GNAS gene, which is imprinted in a tissue-specific manner. Gs alpha is
      paternally silenced in normal pituitary, but Gs alpha imprinting relaxation is
      found in some tumoral tissue. In addition, Gs alpha mRNA levels are high in some
      somatotroph adenomas not bearing the active Gs alpha mutant, the gsp oncogene. In
      this study, the impact of loss of imprinting on Gs alpha expression level and on
      tumoral phenotype has been investigated. We compared the expression and
      imprinting of 4 transcripts of GNAS locus (NESP55, XL alpha s, exon 1A, Gs alpha)
      of 60 somatotroph adenomas with those of 23 lactotroph adenomas. The paternal and
      maternal transcripts were quantified using allele-specific real-time PCR and FokI
      polymorphism. Moreover, the methylation of exon 1A DMR was analyzed. As is the
      case for the gsp oncogene, high Gs alpha expression in gsp- tumors was associated
      with smaller tumor size and better octreotide sensitivity. A strong imprinting
      relaxation (percentage of paternal Gs alpha expression >or=7.5%) was found only
      in gsp- tumors. The loss of Gs alpha imprinting was associated with a decrease in
      exon 1A mRNA expression. Unexpectedly, the methylation status of exon 1A DMR was
      not modified in relaxed tumors. Maternal Gs alpha mRNA level decreased with exon
      1A level, and consequently the loss of Gs alpha imprinting did not induce the
      expected Gs alpha overexpression. Finally, XL alpha s mRNA level correlated with
      that of paternal Gs alpha and of NESP55 showing the complexity of gene regulation
      in the GNAS locus.

PMID- 17514648
TI  - Inhibition of 13-cis retinoic acid-induced gene expression of homeobox B7 by
      thalidomide.
AB  - Thalidomide and 13-cis retinoic acid (RA) show anticancer effects as sole agents
      or in combination with other drugs. However, induction of homeobox (HOX) gene
      expression by 13-cis RA may contribute to tumor progression thereby potentially
      limiting its efficacy. The purpose was to test if thalidomide can inhibit 13-cis
      RA-induced HOXB7 expression and whether thalidomide may enhance the
      antiproliferative effect of 13-cis RA in U343MG glioblastoma cells. Quantitative
      real-time PCR showed significant inhibition of 13-cis RA-induced HOXB7 expression
      by thalidomide with IC(50) approximately 0.1-0.2 microg/ml when given
      simultaneously with 13-cis RA but not when administered 18 h later (p < 0.0001).
      13-cis RA alone inhibited proliferation and colony formation in a concentration
      dependent manner whereas growth inhibition by thalidomide alone at 5-100
      microg/ml was constant at 80-90% of controls. At 10% serum concentration, growth
      inhibition by a combination of the 2 drugs was additive but at 1% serum, growth
      inhibition was synergistic. It is concluded that thalidomide inhibits the RA
      induced HOXB7 expression in glioblastoma cells and that 13-cis RA/thalidomide
      combinations can in principle enhance cytotoxicity. The improved cell kill
      induced by thalidomide is attributed to downregulation of growth stimulatory
      factors induced by 13-cis RA. Implications for the modus operandi of thalidomide
      in embryogenesis are noted.

PMID- 17514649
TI  - Serum androgens and prostate cancer among 643 cases and 643 controls in the
      European Prospective Investigation into Cancer and Nutrition.
AB  - We examined the hypothesis that serum concentrations of circulating androgens and
      sex hormone binding globulin (SHBG) are associated with risk for prostate cancer
      in a case-control study nested in the European Prospective Investigation into
      Cancer and Nutrition (EPIC). Concentrations of androstenedione, testosterone,
      androstanediol glucuronide and SHBG were measured in serum samples for 643
      prostate cancer cases and 643 matched control participants, and concentrations of
      free testosterone were calculated. Conditional logistic regression models were
      used to calculate odds ratios for risk of prostate cancer in relation to the
      serum concentration of each hormone. After adjustment for potential confounders,
      there was no significant association with overall risk for prostate cancer for
      serum total or free testosterone concentrations (highest versus the lowest
      thirds: OR, 1.02; 95% CI, 0.73-1.41 and OR, 1.07, 95% CI, 0.74-1.55,
      respectively) or for other androgens or SHBG. Subgroup analyses showed
      significant heterogeneity for androstenedione by cancer stage, with a significant
      inverse association of androstenedione concentration and risk for advanced
      prostate cancer. There were also weak positive associations between free
      testosterone concentration and risk for total prostate cancer among younger men
      and risk for high-grade disease. In summary, in this large nested case-control
      study, concentrations of circulating androgens or SHBG were not strongly
      associated with risk for total prostate cancer. However, our findings are
      compatible with a positive association of free testosterone with risk in younger
      men and possible heterogeneity in the association with androstenedione
      concentration by stage of disease; these findings warrant further investigation.

PMID- 17514650
TI  - Bladder cancers respond to intravesical instillation of HAMLET (human alpha
      lactalbumin made lethal to tumor cells).
AB  - We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made
      lethal to tumor cells) to establish if intravesical HAMLET application might be
      used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive
      transitional cell carcinomas were included. Nine patients received 5 daily
      intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled
      surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into
      the urine, daily, during the 5 days of instillation. The effect was specific for
      HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did
      not increase cell shedding. Most of the shed cells were dead and an apoptotic
      response was detected in 6 of 9 patients, using the TUNEL assay. At surgery,
      morphological changes in the exophytic tumors were documented by endoscopic
      photography and a reduction in tumor size or change in tumor character was
      detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the
      remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of
      apoptosis and no toxic response. The results suggest that HAMLET exerts a direct
      and selective effect on bladder cancer tissue in vivo and that local HAMLET
      administration might be of value in the future treatment of bladder cancers.

PMID- 17514651
TI  - Functional inactivation of the KLF6 tumor suppressor gene by loss of
      heterozygosity and increased alternative splicing in glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive primary brain
      tumor and possesses a high incidence of 10p loss. The KLF6 (Kruppel-like
      transcription factor) tumor suppressor gene on 10p15 is inactivated by loss of
      heterozygosity (LOH) and/or somatic mutation in a number of human cancers and
      forced expression of KLF6 in GBM lines inhibits their growth and transformation.
      In addition, increased expression of its alternatively spliced, cytoplasmic
      isoform KLF6-SV1 has now been shown to play a role in cancer pathogenesis. On the
      basis of these findings we examined the role of KLF6 and KLF6-SV1 in the
      development and progression of GBM. LOH analysis of 17 primary GBM patient
      samples using KLF6-specific microsatellite markers revealed that 88.2% (15/17)
      had LOH of the KLF6 locus. Interestingly, no KLF6 somatic mutations were
      identified. RNA analysis revealed concomitant decreases in all primary GBM tumors
      (n = 11) by approximately 80% in KLF6 expression (p < 0.001) coupled with
      increased KLF6-SV1 expression (p < 0.001) when compared to normal astrocytes. To
      determine the biological relevance of these findings, we examined the effect of
      KLF6 expression and KLF6-SV1 knockdown in A235 and CRL2020 cell lines.
      Reconstitution of KLF6 decreased cell proliferation by almost 50%, whereas
      targeted KLF6 reduction increased cell proliferation 2.5-4.5 fold. Conversely,
      targeted KLF6-SV1 reduction decreased cell proliferation by 50%. Taken together,
      our findings demonstrate that KLF6 allelic imbalance and decreased KLF6 and
      increased KLF6-SV1 expression are common findings in primary GBM tumors, and
      these changes have antagonistic effects on the regulation of cellular
      proliferation in GBM cell lines.

PMID- 17514652
TI  - Somatic mutations of mitochondrial genome in early stage breast cancer.
AB  - The complete mitochondrial genomes of the primary cancerous, matched
      paracancerous normal and distant normal tissues from 10 early-stage breast cancer
      patients were analyzed in this study, with special attempt (i) to investigate
      whether the reported high frequency of mitochondrial DNA (mtDNA) somatic
      mutations in breast cancer could be repeated under a stringent data quality
      control, and (ii) to characterize the spectrum of mtDNA somatic mutations in
      Chinese breast cancer patients and evaluate their potential significance in early
      cancer diagnosis. Two heteroplasmic somatic transitions (T2275C and A8601G) were
      identified in our samples. The transition A8601G was present in the primary
      cancerous and paracancerous normal tissues from patient no. 3. Transition T2275C
      was found in the primary cancerous tissue but not in other normal tissues from
      patient no. 6; this transition has been reported in the colonic crypts and is
      located at a highly conserved site in the 16S rRNA gene. Subsequent cloning
      sequencing confirmed the absence of both mutations in the distant normal tissues
      from the 2 patients. The overall rate of somatic mutations in our patients was
      much lower than those of previous studies of breast cancer. Our results gave
      support to the recent claim that the high frequency of mtDNA somatic mutations in
      cancer studies is overestimated. Based on the mtDNA mutation pattern in early
      stage breast cancer observed in this study, we cautioned the enthusiasm and
      efforts to look for somatic mutations that were of diagnostic value in cancer
      early detection.

PMID- 17514653
TI  - Human papillomavirus infection among 100 oesophageal cancer cases in the People's
      Republic of China.

PMID- 17514654
TI  - Immunotherapy with dendritic cells for prostate cancer.
AB  - Radical prostatectomy for prostate cancer is followed by PSA recurrence in up to
      40% of patients. One third of patients with biochemical relapse progress to
      uncurable metastatic disease. Therefore, alternative treatment modalities are
      needed both in the situation of PSA recurrence and in hormone-refractory disease.
      Dendritic cells (DC) are the most powerful antigen-presenting cells, able to
      prime naive T-cells and to break peripheral tolerance and thus induce tumor
      immune responses. More than 400 prostate cancer patients have been treated with
      DC-based immunotherapy to date, and immune responses have been reported in two
      thirds of these, resulting in clinical responses in almost half of the patients
      treated. Most responses, however, were modest and transient. Therefore,
      mechanisms of treatment failure and possibilities to improve vaccination efficacy
      are being discussed.

PMID- 17514655
TI  - Fate and clinical significance of saphenofemoral junction tributaries following
      endovenous laser ablation of great saphenous vein.
AB  - BACKGROUND: Unlike surgery, endovenous laser ablation (EVLA) abolishes great
      saphenous vein (GSV) reflux but does not specifically interrupt the GSV
      tributaries at the groin. The fate and clinical significance of these tributaries
      were assessed in a prospective study. METHODS: Eight-one legs (70 patients)
      underwent colour flow duplex ultrasonography 12 months after GSV ablation for
      primary varicose veins. Saphenofemoral junction (SFJ) reflux, tributary patency,
      and recurrent or residual varicosities were recorded, and Aberdeen Varicose Vein
      Severity Scores (AVVSS) were compared with pretreatment values. RESULTS: The GSV
      had recanalized without evidence of reflux in two patients. None of the 81 legs
      showed SFJ reflux although one or more patent tributaries were visible in 48 (59
      per cent); all were competent. In 32 legs (40 per cent) there was flush GSV
      occlusion with the SFJ and no tributaries were detectable. One leg showed
      evidence of neovascularization in the groin. AVVSS values were similar in groups
      with or without visible tributaries, both before and after EVLA: median
      (interquartile range) 13.9 (7.6-19.2) before EVLA and 2.9 (0.6-4.8) at follow-up
      in patients with visible tributaries, and 14.9 (9.2-20.2) and 3.1 (0.8-5.1)
      respectively in those without. Recurrent varicosities were present in one leg
      only, due to an incompetent mid-thigh perforating vein. CONCLUSION: Persistent
      non-refluxing GSV tributaries at the SFJ did not appear to have an adverse impact
      on clinical outcome 1 year after successful EVLA of the GSV.

PMID- 17514656
TI  - Effect of chitosan molecular weight and deacetylation degree on hemostasis.
AB  - Comparative studies have been carried out among solid-state chitosan soliquoid,
      chitosan acetic acid physiological saline solution, and carboxymethyl chitosan
      physiological saline solution to discover the hemostatic effect of molecular
      weight (M(w)) and deacetylation degree (DA) of chitosan. It was found that solid
      state chitosan and chitosan acetic acid physiological saline solution performed
      different hemostatic mechanisms. When blood mixed with chitosan acetic acid
      physiological saline solution, the erythrocytes aggregated and were deformed. The
      DA, especially a low DA, in the chitosan acetic acid physiological saline
      solution, had a significant effect on the unusual aggregation and deformation of
      erythrocytes, compared with the effect of M(w) within a range between 10(5) and
      10(6). However, this phenomenon could not be observed in solid-state chitosan
      soliquoid. Solid-state chitosan with a low DA absorbed more platelets and was
      more hemostatic. Carboxymethyl chitosan physiological saline solution had nothing
      to do with the aggregation and deformation of erythrocytes but caused local
      rouleau. The values of thrombin time (TT), prothrombin time (PT), activated
      partial thromboplastin time (APTT), and fibrinogen concentration (FIB) were
      measured after the blood was mixed with solid-state chitosan soliquoid, chitosan
      acetic acid physiological saline solution, and carboxymethyl chitosan
      physiological saline solution, separately. The results demonstrated that
      coagulation factors might not be activated by them.

PMID- 17514658
TI  - Outcome following bypass, and proximal and distal ligation of popliteal aneurysms
      (Br J Surg 2007; 94: 179-182).

PMID- 17514660
TI  - Letter 2: non-patient factors related to rates of ruptured appendicitis (Br J
      Surg 2007; 94: 214-221).

PMID- 17514661
TI  - Joining characteristics of orthodontic wires with laser welding.
AB  - Laser welding 0.016 x 0.022 in. beta-Ti, Ni-Ti, and Co-Cr-Ni orthodontic wires
      was investigated by measuring joint tensile strength, measuring laser penetration
      depth, determining metallurgical phases using micro X-ray diffraction (micro
      XRD), and examining microstructures with an scanning electron microscope (SEM).
      Welding was performed from 150 to 230 V. Mean tensile strength for Ni-Ti groups
      was significantly lower (p < 0.05) than for most other groups of laser-welded
      specimens. Although mean tensile strength for beta-Ti and Co-Cr-Ni was
      significantly lower than for control specimens joined by silver soldering, it was
      sufficient for clinical use. The beta-Ti orthodontic wire showed deeper
      penetration depth from laser welding than the Ni-Ti and Co-Cr-Ni orthodontic
      wires. Micro-XRD patterns of laser-welded beta-Ti and Ni-Ti obtained 2 mm from
      the boundary were similar to as-received specimens, indicating that original
      microstructures were maintained. When output voltages of 190 V and higher were
      used, most peaks from joint areas disappeared or were much weaker, perhaps
      because of a directional solidification effect, evidenced by SEM observation of
      fine striations in welded beta-Ti. Laser welding beta-Ti and Co-Cr-Ni wires may
      be acceptable clinically, since joints had sufficient strength and metallurgical
      phases in the original wires were not greatly altered.

PMID- 17514662
TI  - Platelet function and antiplatelet therapy.
AB  - BACKGROUND: Platelets have roles other than haemostasis and many are relevant to
      surgical practice. This review examines both the pathophysiology of platelets in
      haemostasis and thrombosis, and other roles of clinical importance. METHODS: A
      literature review of the various functional roles of platelets was performed
      (Medline search, English language) including their action in inflammation (in
      particular in atherothrombosis), antimicrobial defence and tumour growth. Current
      clinical evidence for antiplatelet therapy is also reviewed. RESULTS AND
      CONCLUSION: Platelet functions are multiple, complex and not limited to
      haemostasis. Understanding of platelet pathophysiology continues to grow and this
      is relevant to many aspects of surgical practice, particularly the clinical use
      of antiplatelet therapy.

PMID- 17514663
TI  - Preparation and characterization of novel hybrid of chitosan-g-PDMS and sodium
      montmorrilonite.
AB  - Preparation and properties of Chitosan (CS)-clay nanocomposites grafted with
      polydimethyl siloxane (PDMS) with different clay ratios are herein discussed. CS
      is intercalated into sodium montmorrilonite and PDMS is grafted onto CS under UV
      irradiation. Sample films of CS intercalated into clay and grafted with PDMS were
      prepared by solvent casting method with varying amount of nanoclay and PDMS. They
      were characterized by conventional techniques such as X-ray diffractometry,
      fourier transform infrared spectroscopy, (13)C NMR, thermo gravimetric analysis,
      and differential thermal analysis. Sorption behavior of samples has been followed
      by measuring swelling degree and issues on the interactions of biopolymers with
      clay are also discussed. The water absorption of composites films reduces with an
      increase in the amount of incorporated clay. This is due to the barrier formation
      in the form of cross-linking points, which prevents water permeation into CS. The
      amount of adsorbed water is more, when the amount of CS exceeds the amount of
      PDMS. This shows high water retention capacity of CS.

PMID- 17514665
TI  - Long-term follow-up of a randomized clinical trial of non-mesh versus mesh repair
      of primary inguinal hernia (Br J Surg 2007; 94: 506-510).

PMID- 17514666
TI  - Fifteen-year follow-up of a randomized clinical trial of ultrasonographic
      screening for abdominal aortic aneurysms.
AB  - BACKGROUND: Long-term benefits of screening for abdominal aortic aneurysm (AAA)
      are uncertain. These are the final results of a randomized controlled screening
      trial for AAA in men, updating those reported previously. Benefit and compliance
      over a median 15-year interval were examined. METHODS: One group of men were
      invited for ultrasonographic AAA screening, and another group, who received
      standard care, acted as controls. A total of 6040 men aged 65-80 years were
      randomized to one of the two groups. Outcome was monitored in terms of AAA
      related events (surgery or death). RESULTS: In the group invited for screening,
      AAA-related mortality was reduced by 11 per cent (from 1.8 to 1.6 per cent,
      hazard ratio 0.89) over the follow-up interval. Screening detected an AAA in 170
      patients; 17 of these died from an AAA-related cause, seven of which might have
      been preventable. The incidence of AAA rupture after an initially normal scan
      increased after 10 years of follow-up, but was still low overall (0.56 per 1000
      person-years). CONCLUSION: Screening with a single ultrasonography scan still
      conferred a benefit at 15 years, although the results were not significant for
      this population size. Fewer than half of the AAA-related deaths in those screened
      positive could be prevented. REGISTRATION NUMBER: ISRCTN 00079388
      (http://www.controlled-trials.com).

PMID- 17514667
TI  - No effect of bone morphogenetic protein-7 (OP-1) on the incorporation of impacted
      bone grafts in a realistic acetabular model.
AB  - Bone morphogenetic proteins (BMPs) accelerate bone repair in experimental and
      clinical conditions. Impacted Morsellized Cancellous Bone grafts (MCB) are
      successfully used to reconstruct bone defects after failed hip implants. The main
      question in this study was if BMP-7 (OP-1) mixed with MCB could accelerate the
      incorporation of MCB and prevents the formation of a soft tissue interface after
      remodeling of the MCB. A large loaded defect in the acetabulum of goats was
      reconstructed with a wire mesh and with MCB or MCB mixed with OP-1. After 6
      weeks, no differences were found in the revascularization process, in the number
      of osteoclasts resorbing the MCB, and in the thickness and appearance of the
      fibrous interface between MCB with or without OP-1. After 6 weeks, enchondral
      bone had formed in the bone graft layer and on the periosteal anterior and
      superior rim in the OP-1 group only. More periosteal bone and more bone in the
      holes of the mesh had been formed in most OP-1 goats. Most MCB was replaced by
      new lamellar bone after 15 weeks in both groups. We speculate that during or
      directly after impaction most of the OP-1 is released from the carrier inducing
      an early effect outside the reconstructive layer at the periosteal side of the
      acetabulum. Probably most OP-1 has left the reconstruction by the time new
      vessels and progenitors reached the bone graft. These results do not support the
      use of OP-1 in impaction bone grafting in patients.

PMID- 17514668
TI  - Multicentre randomized clinical trial of mechanical bowel preparation in elective
      colonic resection.
AB  - BACKGROUND: Recent studies have suggested that MBP does not lower the risk of
      postoperative septic complications after elective colorectal surgery. This
      randomized clinical trial assessed whether preoperative MBP is beneficial in
      elective colonic surgery. METHODS: A total of 1505 patients, aged 18-85 years
      with American Society of Anesthesiologists grades I-III, were randomized to MBP
      or no MBP before open elective surgery for cancer, adenoma or diverticular
      disease of the colon. Primary endpoints were cardiovascular, general infectious
      and surgical-site complications within 30 days, and secondary endpoints were
      death and reoperations within 30 days. RESULTS: A total of 1343 patients were
      evaluated, 686 randomized to MBP and 657 to no MBP. There were no significant
      differences in overall complications between the two groups: cardiovascular
      complications occurred in 5.1 and 4.6 per cent respectively, general infectious
      complications in 7.9 and 6.8 per cent, and surgical-site complications in 15.1
      and 16.1 per cent. At least one complication was recorded in 24.5 per cent of
      patients who had MBP and 23.7 per cent who did not. CONCLUSION: MBP does not
      lower the complication rate and can be omitted before elective colonic resection.
      REGISTRATION NUMBER: ISRCTN28535118 (http://www.controlled-trials.com).

PMID- 17514669
TI  - Oxidation of proteins adsorbed on hemodialysis membranes and model materials.
AB  - The cleaning of cellulosic hemodialysis membrane Cuprophan and model materials
      (glass; polystyrene and polypropylene, as such and surface-oxidized), conditioned
      by adsorption of blood plasma proteins (HSA, fibrinogen, IgG) was investigated in
      vitro. Sodium hypochlorite (NaClO) and Renalin, a product containing hydrogen
      peroxide and peroxyacetic acid, were used as cleaning reagents. X-ray
      photoelectron spectroscopy and the use of radiolabeled fibrinogen demonstrated
      the presence of varying amounts of a polypeptidic residue, with sulfur brought to
      a high oxidation stage (sulfonate-like). The trends were the same for the three
      proteins regarding the effectiveness of the oxidizer and the influence of the
      surface properties. NaClO was much more effective than Renalin to remove the
      adsorbed proteins. The proteins adsorbed on Cuprophan were more sensitive to the
      oxidizers, when compared with proteins adsorbed on other materials. This may be
      due to both the lower protein-surface affinity, as indicated by radiochemical
      measurements, and the sensitivity of the material itself to the oxidizer, as
      revealed by weight loss measurements. These results support the attribution of
      hemocompatibility improvement after regeneration of Cuprophan with Renalin to the
      masking of the activating surface by a residue from previously adsorbed proteins.

PMID- 17514670
TI  - Effect of serum metabolites of Pueraria lobata in rats on peripheral nerve
      regeneration: in vitro and in vivo studies.
AB  - This study provides in vitro and in vivo evaluation of rat serum metabolites of
      the Pueraria lobata (SMP) on peripheral nerve regeneration. In the in vitro
      study, we found that the SMP caused a marked enhancement of the nerve growth
      factor (NGF)-mediated neurite outgrowth and the expression of synapsin I from
      PC12 cells. In the in vivo study, silicone rubber chambers filled with the SMP
      were used to bridge a 10-mm sciatic nerve defect in rats. At the conclusion of 8
      weeks, animals from the groups treated with the SMP had a relatively more mature
      structure with larger mean values of myelinated axon number, endoneurial area,
      and total nerve area when compared with those in the controls receiving the
      saline only. These results suggest that the serum metabolites of Pueraria lobata
      can be a potential nerve growth-promoting factor.

PMID- 17514671
TI  - Randomized clinical trial of single- versus multiple-dose antimicrobial
      prophylaxis in gastric cancer surgery.
AB  - BACKGROUND: The optimum duration of antimicrobial prophylaxis in elective gastric
      cancer surgery is still open to question. This multicentre randomized clinical
      trial compared a single-dose with a multiple-dose regimen of antimicrobial
      prophylaxis for prevention of surgical-site infection. METHODS: Between May 2001
      and December 2004, 501 patients undergoing elective surgery for gastric cancer in
      ten centres were allocated randomly to single- or multiple-dose antimicrobial
      prophylaxis. The primary outcome measure was the incidence of surgical-site
      infection, analysed by intention to treat. RESULTS: Some 243 patients who
      received a single dose and 243 who received multiple doses of antibiotics were
      included in the final analysis. The surgical-site infection rate was 9.5 per cent
      (23 of 243) and 8.6 per cent (21 of 243) respectively (difference 0.9 (95 per
      cent confidence interval - 4.3 to 5.9) per cent). Antimicrobial prophylaxis had
      no major adverse effects. CONCLUSION: The incidence of surgical-site infection in
      elective gastric cancer surgery was similar with both antibiotic prophylaxis
      regimens.

PMID- 17514672
TI  - Human osteoblast-like cells response to nanofunctionalized surfaces for tissue
      engineering.
AB  - Cells are sensitive both to the micro/nanotopographic and chemical features of
      their surrounding environment. The engineering of the surface properties of
      biomaterials is then critical to develop bioactive devices with which to elicit
      appropriate cellular responses. To this regard, the layer by layer (LBL) self
      assembly technique represents a simple and versatile method to modify surface
      properties by the deposition of ultrathin films with specific and predetermined
      properties. In this work biomimetic coatings containing fibronectin, an adhesive
      glycoprotein of the extracellular matrix, were assembled by means of the LBL
      technique, and tested for the growth of MG63 human osteoblast-like cells, in
      order to evaluate their potential for the treatment of materials employed in bone
      tissue engineering. As a first step the assembly process was optimized by quartz
      crystal microbalance measurements and subsequently was repeated on
      nickel/titanium, silicon and glass samples. The results obtained from the
      investigation of cell response to the modified surfaces, put in evidence that the
      deposited nanostructured ultrathin films are effective in promoting cell
      proliferation. Our results show the high potential of the developed bioactive
      coatings for the engineering of biomimetic implants and for the optimization of
      their integration with the surrounding tissues.

PMID- 17514673
TI  - Evolution in perioperative management of patients undergoing oesophagectomy.

PMID- 17514674
TI  - Priorities in the management of abdominal aortic aneurysm.

PMID- 17514675
TI  - Proteomic analysis of day-night variations in protein levels in the rat pineal
      gland.
AB  - The pineal gland secretes the hormone melatonin. This secretion exhibits a
      circadian rhythm with a zenith during night and a nadir during day. We have
      performed proteome analysis of the superficial pineal gland in rats during
      daytime and nighttime. The proteins were extracted and subjected to 2-DE. Of 1747
      protein spots revealed by electrophoresis, densitometric analysis showed the up
      regulation of 25 proteins during nighttime and of 35 proteins during daytime.
      Thirty-seven of the proteins were identified by MALDI-TOF MS. The proteins up
      regulated during the night are involved in the Krebs cycle, energy transduction,
      calcium binding, and intracellular transport. During the daytime, enzymes
      involved in glycolysis, electron transport, and also the Krebs cycle were up
      regulated as well as proteins taking part in RNA binding and RNA processing. Our
      data show a prominent day-night variation of the protein levels in the rat pineal
      gland. Some proteins are up-regulated during the night concomitant with the
      melatonin secretion of the gland. Other proteins are up-regulated during the day
      indicating a pineal metabolism not related to the melatonin synthesis.

PMID- 17514676
TI  - Hypervalent iodine-mediated aziridination of alkenes: mechanistic insights and
      requirements for catalysis.
AB  - By detailed study of the possible side reactions in the previously reported
      aziridination of alkenes with N-aminoheterocycles mediated by hypervalent iodine
      reagents, the requirements to make this reaction catalytic in iodoarene have been
      determined. The reaction requires an oxidant that will oxidise iodoarenes but
      that does not oxidise alkenes, but it is possible that no such oxidant actually
      exists! A method in which the hypervalent iodine reagent can be recycled without
      the need for reisolation is possible. Further study into the mechanism of this
      reaction gives tentative evidence that the reaction proceeds through formation of
      an aminoiodane that reacts directly with the alkene, contrary to previous
      literature reports in which an acetoxyamine intermediate is suggested. The
      temperature effect of this reaction is remarkable.

PMID- 17514677
TI  - Fluoranthene metabolism and associated proteins in Mycobacterium sp. JS14.
AB  - Fluoranthene is a polycyclic aromatic hydrocarbon (PAH) commonly present in PAH
      contaminated soils. We studied fluoranthene catabolism and associated proteins in
      Mycobacterium sp. JS14, a bacterium isolated from a PAH-contaminated soil in Hilo
      (HI, USA). Fluoranthene degrades in at least three separated pathways via 1
      indanone, 2',3'-dihydroxybiphenyl-2,3,-dicarboxylic acid, and naphthalene-1,8
      dicarboxylic acid. Part of the diverse catabolism is converged into phthalate
      catabolism. An increased expression of 25 proteins related to fluoranthene
      catabolism is found with 1-D PAGE or 2-DE and nano-LC-MS/MS. Detection of
      fluoranthene catabolism associated proteins coincides well with its multiple
      degradation pathways that are mapped via metabolites identified. Among the up
      regulated proteins, PAH ring-hydroxylating dioxygenase alpha-subunit and beta
      subunit and 2,3-dihydroxybiphenyl 1,2-dioxygenase are notably induced. The up
      regulation of trans-2-carboxybenzalpyruvate hydratase suggests that some of
      fluoranthene metabolites may be further degraded through aromatic dicarboxylic
      acid pathways. Catalase and superoxide dismutase were up-regulated to control
      unexpected oxidative stress during the fluoranthene catabolism. The up-regulation
      of chorismate synthase and nicotine-nucleotide phosphorylase may be necessary for
      sustaining shikimate pathway and pyrimidine biosynthesis, respectively. A
      fluoranthene degradation pathway for Mycobacterium sp. JS14 was proposed and
      confirmed by proteomic study by identifying almost all the enzymes required
      during the initial steps of fluoranthene degradation.

PMID- 17514678
TI  - Proteome phenotyping of acid stress-resistant mutants of Lactococcus lactis
      MG1363.
AB  - To cope with medium acidity, Lactococcus lactis has evolved a number of inducible
      mechanisms commonly referred as acid stress response. To better understand the
      molecular basis of this response, several mutants constitutively tolerant to
      acidity were previously obtained by insertional random mutagenesis of L. lactis
      MG1363. Mutants in which the GMP synthase gene (i.e. guaA), the (p)ppGpp synthase
      gene (i.e. relA*) or the high affinity phosphate transport system (i.e. pstS) are
      inactivated are further characterized in this study. 2-DE was performed and
      showed that 42, 26, and 35 protein spots are positively deregulated in the guaA,
      relA*, and pstS mutants, respectively, as compared to the wild-type strain. Most
      of these proteins were identified by MS. Proteomes comparison of the mutants
      guaA, relA*, and pstS as well as the acid adaptation proteome of the wild-type
      strain revealed (i) the presence of numerous overlaps and (ii) that only five
      proteins were overexpressed in the four conditions, suggesting that these
      proteins play a crucial role in the constitutive acid stress tolerance of the
      mutants and in the acid tolerance response of the wild-type strain.

PMID- 17514679
TI  - A further proteomic study on the effect of iron in the human pathogen Trichomonas
      vaginalis.
AB  - Iron is an essential element to support the growth and survival of Trichomonas
      vaginalis. It plays a critical role in the host-parasite interaction, and
      modulates the expression of virulence factors in this protozoan. In this work,
      parasites grown in iron-rich and iron-depleted media were analyzed by (i) light
      and scanning electron microscopy and (ii) 2-DE and MS. Withdrawal of iron from
      the culture medium resulted in dramatic changes in both the morphology and in the
      proteome pattern of T. vaginalis. Trophozoites underwent transformation from
      ellipsoid or amoeboid forms to rounded cells, whose flagella and axostyle were
      internalized. Forty-five proteins differentially expressed in parasites
      cultivated in the absence of iron were identified. In iron-depleted parasites,
      enzymes involved in energetic metabolism, proteolysis and hydrogenosomal iron
      sulfur (Fe-S) proteins were down-regulated or even suppressed. Among up-regulated
      proteins, six isoforms of actin were detected. In addition, phosphoenolpyruvate
      carboxykinase, putative lactate dehydrogenase, and putative adenosine
      triphosphatase were also up-regulated or were exclusively observed in gels
      related to iron-depleted parasites. Our data demonstrate that iron has a pivotal
      role in the regulation of the morphological transformation of T. vaginalis and
      modulates the expression of both Fe-S and non-Fe-S proteins in the parasite.

PMID- 17514680
TI  - Proteome analysis of proliferative response of bystander cells adjacent to cells
      exposed to ionizing radiation.
AB  - Recently (Cytometry 2003, 56A, 71-80), we reported that direct cell-to-cell
      contact is required for stimulating proliferation of bystander rat liver cells
      (WB-F344) cocultured with irradiated cells, and neither functional gap junction
      intercellular communication nor long-range extracellular factors appear to be
      involved in this proliferative bystander response (PBR). The molecular basis for
      this response is unknown. Confluent monolayers of WB-F344 cells were exposed to 5
      Gray (Gy) of gamma-rays. Irradiated cells were mixed with unirradiated cells and
      co-cultured for 24 h. Cells were harvested and protein expression was examined
      using 2-DE. Protein expression was also determined in cultures of unirradiated
      and 5-Gy irradiated cells. Proteins were identified by MS. Nucleophosmin (NPM)-1,
      a multifunctional nucleolar protein, was more highly expressed in bystander cells
      than in either unirradiated or 5-Gy irradiated cells. Enolase-alpha, a glycolytic
      enzyme, was present in acidic and basic variants in unirradiated cells. In
      bystander and 5-Gy irradiated cells, the basic variant was weakly expressed,
      whereas the acidic variant was overwhelmingly present. These data indicate that
      the presence of irradiated cells can affect NPM-1 and enolase-alpha in adjacent
      bystander cells. These proteins appear to participate in molecular events related
      to the PBR and suggest that this response may involve cellular defense,
      proliferation, and metabolism.

PMID- 17514681
TI  - Proteomics of ionically bound and soluble extracellular proteins in Medicago
      truncatula leaves.
AB  - A large proportion of the apoplast proteome resides in the intercellular fluid
      (IF) or is ionically bound (IB) to the wall matrix. A combined analysis of IF and
      IB proteins of the Medicago truncatula leaf apoplast was performed. 2-DE analyses
      demonstrated the reproducible presence of 220 IF and 84 IB proteins in the
      apoplast. These two protein populations were largely distinct; 22 proteins could
      be spatially matched, but MALDI-TOF/TOF analyses suggested a considerably smaller
      number had common identities. MALDI-TOF/TOF characterisation identified 81
      distinct proteins. Analyses of selected IF proteins (45) indicated 17 distinct
      proteins with mainly defence-related functions, whereas analyses of IB proteins
      (70) identified 63 distinct proteins of diverse natures, including proteins of
      non-canonical natures. The presence of non-canonical proteins in IB extracts is
      discussed in the light of evidence supporting a low level of contamination of
      purified walls from symplastic proteins. This work indicates that IB and IF
      proteins are functionally distinct fractions of the apoplast. The data obtained
      complements earlier studies of the Medicago proteome and therefore will be useful
      in future studies investigating the role of apoplastic proteins in plant
      processes.

PMID- 17514682
TI  - Evolution of 2-DE protein patterns in a mussel hybrid zone.
AB  - Protein expression patterns were compared in mussels from a hybrid zone between
      the two species Mytilus edulis and M. galloprovincialis using 2-DE. Significant
      differences in expression pattern were observed between species and between
      mussels within species. Hybrid mussels had more variable protein expression
      patterns than mussels of each species. This could be due to segregation at
      expression modifier loci in the hybrids. It is proposed that unusual hybrid
      expression patterns might contribute to postzygotic isolation, if such patterns
      reduce fitness. The use of proteomic data for testing evolutionary models, as in
      many transcriptomics studies, is explored with results consistent with the
      expectations of neutral theory.

PMID- 17514683
TI  - Comparison of the nuclear proteomes of mammary epithelial cells at different
      stages of functional differentiation.
AB  - The progression of stem cells to proliferating progenitor cells and finally to a
      quiescent differentiated state is a hallmark of organ development. This process
      proceeds through distinct steps and is regulated through cell-cell interactions
      and by systemically and locally acting factors. We have established a cell
      culture system which recapitulates features of mammary gland development in vitro
      and allows the comparison of three characteristic differentiation stages. Cell
      fate decisions relating to proliferation and differentiation are dependent on the
      function of proteins in the nucleus. Therefore, we have applied proteomic
      approaches, including 1- and 2-DE coupled with MS and a gel-free system, called
      protein sequence tag technology (PST), to assess the changes in the nuclear
      protein composition during differentiation of mammary epithelial cells. We
      identified about 250 individual proteins which are present in the nucleus of
      proliferating and functionally differentiated mammary epithelial cells. We
      functionally categorised the differentially expressed proteins and identified a
      multitude of proteins that regulate gene expression at the transcriptional or
      post-transcriptional level. This analysis greatly enriches our global view of the
      dynamic changes of nuclear proteins during the development of mammary epithelial
      cells and suggests models for the control of differentiation-specific protein
      expression.

PMID- 17514684
TI  - Identification of biomarkers associated with the development of hepatocellular
      carcinoma in CuZn superoxide dismutase deficient mice.
AB  - To identify biomarkers associated with the development of hepatocellular
      carcinoma (HCC) in CuZn superoxide dismutase (CuZnSOD, Sod1) deficient mice, 2-DE
      followed by MS analysis was carried out with liver samples obtained from 18-month
      old Sod1-/- and +/+ mice. The intracellular Ca binding protein, regucalcin (RGN),
      showed a divergent alteration in Sod1-/- samples. Whereas elevated RGN levels
      were observed in -/- samples with no obvious neoplastic changes, marked reduction
      in RGN was observed in -/- samples with fully developed HCC. GST mu1 (GSTM1), on
      the other hand, showed a significant increase only in the neoplastic regions
      obtained from Sod1-/- livers. No change in GSTM1 was observed in the surrounding
      normal tissues. Marked reduction was observed in two intracellular lipid
      transporters, fatty acid binding protein 1 (FABP1) and major urinary protein 11
      and 8 (MUP 11&8), in Sod1-/- samples. Analysis of additional samples at 18-22
      months of age showed a three-fold increase in enolase activities in Sod1-/-
      livers. Consistent with previous findings, carbonic anhydrase 3 (CAIII) levels
      were significantly reduced in Sod1-/- samples, and immunohistochemical analysis
      revealed that the reduction was not homogenous throughout the lobular structure
      in the liver.

PMID- 17514685
TI  - Valsartan reverses post-translational modifications of the delta-subunit of ATP
      synthase during in vivo canine reperfused myocardial infarction.
AB  - To determine whether reperfused myocardial infarction (RMI) induces PTM of the
      delta-subunit of the mitochondrial metabolic enzyme ATP synthase (ATP/delta) in
      the ischemic zone (IZ) and whether this can be reversed by the angiotensin II
      type 1 receptor (AT(1)R) blocker valsartan, we applied a pharmaco-proteomics
      approach in canine RMI hearts with or without valsartan pretreatment. Using the 2
      DE technique, we identified differential regional expression of ATP/delta in the
      IZ compared to the non-ischemic zone (NIZ), with an approximately 2-fold increase
      in the IZ that was normalized by valsartan. Furthermore in the IZ, RMI triggered
      S-nitrosylation of cysteine-100, nitration of the two tyrosines 88 and 225, and
      hydroxylation of lysine-182 in ATP/delta followed by its myristoylation.
      Importantly, valsartan abolished these modifications of ATP/delta in the IZ,
      triggered phosphorylation of serine-76 in both the IZ and NIZ, and decreased
      necrosis, apoptosis, left ventricular dysfunction and remodeling. Thus, AT(1)R
      blocker-induced cardioprotection during RMI is associated with phosphorylation of
      ATP/delta and inhibition of nitric oxide-related chemical modifications such as S
      nitrosylation, nitration and hydroxylation. Targeting specific PTMs during RMI,
      such as those of ATP/delta with AT(1)R blockade, might be a potentially powerful
      novel therapeutic approach. However, the identification of S-nitrosylation was
      putative and requires MS/MS verification.

PMID- 17514686
TI  - Protein prenylation in an insect cell-free protein synthesis system and
      identification of products by mass spectrometry.
AB  - To evaluate the ability of an insect cell-free protein synthesis system to carry
      out proper protein prenylation, several CAIX (X indicates any C-terminal amino
      acid) sequences were introduced into the C-terminus of truncated human gelsolin
      (tGelsolin). Tryptic digests of these mutant proteins were analyzed by MALDI-TOF
      MS and MALDI-quadrupole-IT-TOF MS. The results indicated that the insect cell
      free protein synthesis system possesses both farnesyltransferase (FTase) and
      geranylgeranyltransferase (GGTase) I, as is the case of the rabbit reticulocyte
      lysate system. The C-terminal amino acid sequence requirements for protein
      prenylation in this system showed high similarity to those observed in rat
      prenyltransferases. In the case of rhoC, which is a natural geranylgeranylated
      protein, it was found that it could serve as a substrate for both
      prenyltransferases in the presence of either farnesyl or geranylgeranyl
      pyrophosphate, whereas geranylgeranylation was only observed when both prenyl
      pyrophosphates were added to the in vitro translation reaction mixture. Thus, a
      combination of the cell-free protein synthesis system with MS is an effective
      strategy to analyze protein prenylation.

PMID- 17514687
TI  - PtCl2-catalyzed hydrative cyclization of trialkyne functionalities to form
      bicyclic spiro ketones.

PMID- 17514688
TI  - Superoxide does react with peroxides: direct observation of the Haber-Weiss
      reaction in the gas phase.

PMID- 17514689
TI  - Topotactic linear radical polymerization of divinylbenzenes in porous
      coordination polymers.

PMID- 17514690
TI  - Thermal activation of methane by group 10 metal hydrides MH+: the same and not
      the same.

PMID- 17514691
TI  - Stabilization of tetrafluorobutatriene by complex formation.

PMID- 17514692
TI  - Synthesis and structure-activity relationship of cytotoxic marine
      cyclodepsipeptide IB-01212 analogues.
AB  - Several recently discovered marine products have remarkable in vitro and in vivo
      anticancer profiles against a wide range of tumor cell lines. Some of these
      compounds are currently in clinical trials. These compounds show complex
      structures and mechanisms of action of interest. Herein, we describe the
      preparation of a series of totally synthetic molecules that are structurally
      related to the natural marine product IB-01212 and evaluated them as antitumor
      agents. For this, total solid-phase syntheses of the products were performed in
      parallel by two distinct routes: linear synthesis and convergent synthesis.
      Structural modifications were introduced in several residue positions to afford
      21 IB-01212 analogues for structure-relationship studies. An increase in the
      number of methyl groups in the macrocycle enhanced cytotoxic activity. Also, the
      replacement of an ester bond by an amide bond favored antitumor activity against
      several human cell lines. In addition, the L configuration analogues were more
      active against all the tumor cell lines than those containing the D
      configuration. A significant increase in the size and asymmetry of the macrocycle
      diminished biological activity with respect to that of IB-01212. These results
      are of great value for the discovery of new and more effective anticancer agents.

PMID- 17514693
TI  - Final 12-year follow-up of surgery versus surveillance in the UK Small Aneurysm
      Trial.
AB  - BACKGROUND: The aim was to determine whether early open surgical repair would
      benefit patients with small abdominal aortic aneurysm compared with surveillance
      on long-term follow-up. METHODS: The 1090 patients who were enrolled into the UK
      Small Aneurysm Trial between 1991 and 1995 were followed up for aneurysm repair
      and mortality until November 2005. RESULTS: By November 2005, 714 patients (65.5
      per cent) had died, 929 (85.2 per cent) had undergone aneurysm repair, 150 (13.8
      per cent) had died without aneurysm repair and 11 (1.0 per cent) remained alive
      without aneurysm repair. After 12 years, mortality in the surgery and
      surveillance groups was 63.9 and 67.3 per cent respectively, unadjusted hazard
      ratio 0.90 (P = 0.139). Three-quarters of the surveillance group eventually had
      aneurysm repair, with a 30-day elective mortality of 6.3 per cent (versus 5.0 per
      cent in the early surgery group, P = 0.366). Estimates suggested that the cost of
      treatment was 17 per cent higher in the early surgery group, with a mean
      difference of 1326 pounds. The death rate in these patients was about twice that
      in the population matched for age and sex. CONCLUSION: There was no long-term
      survival benefit of early elective open repair of small abdominal aortic
      aneurysms. Even after successful aneurysm repair, the mortality among these
      patients was higher than in the general population.

PMID- 17514694
TI  - VBHOM, a data economic model for predicting the outcome after open abdominal
      aortic aneurysm surgery.
AB  - BACKGROUND: Vascular Biochemistry and Haematology Outcome Models (VBHOM) adopted
      the approach of using a minimum data set to model outcome. This study aimed to
      test such a model on a cohort of patients undergoing open elective and non
      elective abdominal aortic aneurysm (AAA) repair. METHODS: A binary logistic
      regression model of risk of in-hospital mortality was built from the 2002-2004
      submission to the UK National Vascular Database (NVD) (2718 patients). The subset
      of NVD data items used comprised serum levels of urea, sodium and potassium,
      haemoglobin, white cell count, sex, age and mode of admission. The model was
      applied prospectively using Hosmer-Lemeshow methodology to a test data set from
      the Cambridge Vascular Unit. RESULTS: The validation set contained 327 patients,
      of whom 208 had elective AAA repair and 119 had emergency repair of a ruptured
      AAA. Outcome following elective and non-elective AAA repair could be described
      accurately using the same model. The overall mean predicted risk of death was
      14.13 per cent, and 48 deaths were predicted. The actual number of deaths was 53
      (chi(2) = 8.40, 10 d.f., P = 0.590; no evidence of lack of fit). The model also
      demonstrated good discrimination (c-index = 0.852). CONCLUSION: The VBHOM
      approach has the advantage of using simple, objective clinical data that are easy
      to collect routinely. The VBHOM data items potentially allow prediction of risk
      in an individual patient before aneurysm surgery.

PMID- 17514695
TI  - Patient fitness and survival after abdominal aortic aneurysm repair in patients
      from the UK EVAR trials.
AB  - BACKGROUND: The aim was to use a validated fitness score to determine whether
      fitter patients with a large abdominal aortic aneurysm (AAA) benefited from
      having open rather than endovascular repair. METHODS: The Customized Probability
      Index (CPI) was applied to patients in the Endovascular Aneurysm Repair (EVAR) I
      and II trials. Interaction tests between CPI and randomized group assessed the
      effect of fitness and type of AAA repair on elective 30-day mortality and 4-year
      survival. RESULTS: The mean(s.d.) CPI scores were 3.6(9.3) for 1252 EVAR I
      patients and 10.0(11.3) for 404 EVAR II patients (range - 25 to + 43) (P <
      0.001). The fitness of EVAR I patients was classified as good (579 patients, mean
      CPI - 4.2), moderate (331 patients, mean CPI 5.7) or poor (338 patients, mean CPI
      15.1). Only in the good fitness group did 30-day mortality convincingly favour
      endovascular repair (odds ratio 0.24, P = 0.030), but overall the test of
      interaction was not significant (P = 0.363). For 4-year all-cause and aneurysm
      related mortality, there was no benefit for either treatment across all fitness
      scores (P = 0.281 and P = 0.371 respectively). CONCLUSION: The benefit of
      endovascular repair was most convincing in the fittest patients. There was no
      evidence that the fittest patients benefited more from open surgery.

PMID- 17514698
TI  - Meta-analysis of individual- and aggregate-level data.
AB  - The methodology described here was developed for a systematic review and
      individual participant-level meta-analysis of home safety education and the
      provision of safety equipment for the prevention of childhood accidents. This
      review had a particular emphasis on exploring whether effectiveness was related
      to socio-demographic characteristics previously shown to be associated with
      injury risk. Individual participant data were only made available to us for a
      proportion of the included studies. This resulted in the need for developing a
      new methodology to combine the available data most efficiently. Our objective was
      to develop a (random effects) meta-analysis model that could synthesize both
      individual-level and aggregate-level binary outcome data while exploring the
      effects of binary covariates also available in a combination of individual
      participant and aggregate level data. To add further complication, the studies to
      be combined were a mixture of cluster and individual participant-allocated
      designs.A Bayesian model using Markov chain Monte Carlo methods to estimate
      parameters is described which efficiently synthesizes the data by allowing
      different models to be fitted to the different study design and data format
      combinations available. Initially we describe a model to estimate mean effects
      ignoring the influence of the covariates, and then extend it to include a binary
      covariate. The application of the method is illustrated by application to one
      outcome from the motivating home safety meta-analysis for illustration. Using the
      same general approach, it would be possible to develop further 'tailor made'
      evidence synthesis models to synthesize all available evidence most effectively.

PMID- 17514699
TI  - Paired exchange programmes can expand the live kidney donor pool.
AB  - BACKGROUND: Kidney paired donation (KPD) is an exchange of organs between two
      live donors, who are otherwise ABO incompatible or cross-match positive, and
      their intended recipients. The outcome is the generation of compatible
      transplants conferring an improvement in quality of life and longevity. METHODS:
      Medline was searched for articles on KPD using a combination of keywords.
      Publications focusing on protocols and policy, mathematical modelling, ethical
      controversies, and legal and logistical barriers were identified. RESULTS: Many
      are precluded from transplantation because of incompatibilities with their
      intended donors. KPD has the potential to increase the rate of transplantation by
      facilitating exchange transplants between otherwise incompatible donor-recipient
      couples. Ethical controversies surrounding paired donation include
      confidentiality, conditionality of donation, synchronicity of operations and the
      possibility of disadvantaging blood group O recipients. Logistical barriers
      hampering KPD programmes involve the location of donor surgery and organ
      transport. CONCLUSION: Paired donation may expand the living donor pool by
      providing an alternative successful strategy for incompatible donor-recipient
      couples. Its widespread implementation will depend on resolving ethical and
      logistical constraints.

PMID- 17514701
TI  - Meta-analysis of epidural analgesia versus parenteral opioid analgesia after
      colorectal surgery.
AB  - BACKGROUND: Epidural analgesia (EA) with local anaesthetic is considered to play
      a key role after colorectal surgery. However, its effect on postoperative
      recovery is still a matter of debate. METHODS: A systematic review of randomized
      controlled trials comparing postoperative EA and parenteral opioid analgesia
      after colorectal surgery was performed. The effect on postoperative recovery was
      evaluated in terms of length of hospital stay, pain intensity, duration of
      postoperative ileus, incidence of postoperative complications and side-effects.
      RESULTS: Sixteen trials published between 1987 and 2005 were included. EA
      significantly reduced pain scores and duration of ileus (weighted mean difference
      - 1.55 (95 per cent confidence interval (c.i.) - 2.27 to - 0.84) days). On the
      other hand, it was associated with a significant increase in the incidence of
      pruritus (odds ratio (OR) 4.8 (95 per cent c.i. 1.3 to 17.0)), urinary retention
      (OR 4.3 (1.2 to 15.9)) and arterial hypotension (OR 13.5 (4.0 to 57.7)). EA did
      not influence duration of hospital stay. CONCLUSION: Despite improved analgesia
      and a decrease in ileus, EA has some adverse effects and does not shorten the
      duration of hospital stay after colorectal surgery.

PMID- 17514702
TI  - Protein conduction and negative differential resistance in large-scale
      nanojunction arrays.

PMID- 17514703
TI  - Synthesis and electrical transport of novel channel-structured beta-AgVO3.

PMID- 17514704
TI  - Taking the long view: the prenatal environment and early adolescent overweight.
AB  - The purpose of this study was to assess the independent effects of the prenatal
      environment and cumulated social risks on the likelihood of being overweight at
      age 12/13 years. Maternal prepregnancy weight and smoking during pregnancy were
      the measures of prenatal exposures. Average lifetime per capita income and
      mother's lifetime marital status were the measures of cumulative social risks.
      Analysis of data from the National Longitudinal Survey of Youth's Child-Mother
      file indicated that exposures to tobacco smoke in utero, maternal prepregnancy
      overweight/obesity, and maternal unmarried status were significant risks for
      adolescent overweight. The risk for overweight was reduced by breastfeeding if
      the mother was overweight/obese prepregnancy. Prenatal and early life factors
      were related to adolescent overweight, providing an important window for
      intervention.

PMID- 17514705
TI  - The association of personality type in childhood with violence in adolescence.
AB  - The relationship of personality type at age 6 years to interpersonal violence at
      age 12 years was investigated. Participants from the Child Sample of the National
      Longitudinal Survey of Youth with complete data measures for the three time
      periods were categorized into one of the three personality types at age 6: under
      controlled, resilient, and over-controlled. At age 12, participants assigned to
      the under-controlled personality type 6 years earlier were more likely than those
      assigned to the resilient or over-controlled personality types to report that
      they had hurt someone seriously at least once in the past year. The association
      of childhood personality to interpersonal violence 6 years later was not mediated
      by peer rejection or associations with deviant peers.

PMID- 17514706
TI  - Effects of preoperative therapeutic play on outcomes of school-age children
      undergoing day surgery.
AB  - The purpose of this study was to examine the effects of therapeutic play on
      outcomes of children undergoing day surgery. Two hundred and three children
      admitted for day surgery were invited to participate in a randomized controlled
      trial. The experimental group received therapeutic play; the control group
      received routine information preparation. Children in the experimental group
      reported significantly lower state anxiety scores in pre- and postoperative
      periods and exhibited fewer negative emotions at induction of anesthesia than
      children in the control group. No significant differences were found between the
      two groups in postoperative pain. The study provides some evidence that
      therapeutic play is effective in pre- as opposed to postsurgical management of
      children.

PMID- 17514707
TI  - Correlates of mother-premature infant interactions.
AB  - This study's purpose was to examine whether child characteristics, child illness
      severity, maternal characteristics, maternal psychological well-being, and
      paternal support influenced interactions between 108 premature infants and their
      mothers. Mothers with singletons or more infant illness stress showed more
      positive involvement. Mothers with less infant illness stress, less education, or
      less participation in caregiving by fathers showed more negative control. First
      time mothers and mothers of singletons provided more developmental stimulation.
      Children of younger and White mothers showed more social behaviors. Less maternal
      education and shorter period of mechanical ventilation were associated with
      greater developmental maturity. Greater maternal worry was related to more child
      irritability. These findings are consistent with the developmental science view
      that the mother-premature relationship is a complex, reciprocal process.

PMID- 17514708
TI  - Assessment of caregivers' willingness to participate in an intervention research
      study.
AB  - The purpose of the study was to identify factors that influenced family
      caregivers' decisions to participate in an intervention research study. In
      interviews conducted before and after the intervention, caregivers (n=21)
      described reasons for participation. A focused content analysis was used to
      examine responses. Themes that emerged included: (a) caregivers recognized a need
      for help; (b) expectations and motivations toward change; (c) recognition of self
      worth as caregivers; (d) timeliness of recruitment strategies; (e) support of
      research staff affected recruitment; and (f) caregivers recognized the benefits
      of participation. These findings support the importance of many different
      strategies for effective recruitment of caregivers in future studies.

PMID- 17514709
TI  - Top 10 tips for beginning a program of research.

PMID- 17514710
TI  - Endosomal transport of neurotrophins: roles in signaling and neurodegenerative
      diseases.
AB  - The internalization and retrograde axonal transport of neurotrophin receptors is
      important for their retrograde signal transduction supporting neuronal
      differentiation, plasticity, and survival. To influence transcription,
      neurotrophin signals initiated at synapses have to be conveyed retrogradely to
      the cell body. Signaling endosomes containing neurotrophin receptor signaling
      complexes mediate retrograde neurotrophin signaling from synapses to the nucleus.
      Interestingly, many neurodegenerative diseases, including Alzheimer's disease,
      Niemann Pick disease Type C, and Charcot-Marie-Tooth neuropathies, show
      alterations of vesicular transport, suggesting that traffic jams within neuronal
      processes may cause neurodegeneration. Although most of these diseases are
      complex and may be modulated by diverse pathways contributing to neuronal death,
      altered neurotrophin transport is emerging as a strong candidate influence on
      neurodegeneration. In this article, we review the mechanisms of internalization
      and endocytic trafficking of neurotrophin receptors, and discuss the potential
      roles of perturbations in neurotrophin trafficking in a number of
      neurodegenerative diseases.

PMID- 17514711
TI  - Curiosity and cure: translational research strategies for neural repair-mediated
      rehabilitation.
AB  - Clinicians who seek interventions for neural repair in patients with paralysis
      and other impairments may extrapolate the results of cell culture and rodent
      experiments into the framework of a preclinical study. These experiments,
      however, must be interpreted within the context of the model and the highly
      constrained hypothesis and manipulation being tested. Rodent models of repair for
      stroke and spinal cord injury offer examples of potential pitfalls in the
      interpretation of results from developmental gene activation, transgenic mice,
      endogeneous neurogenesis, cellular transplantation, axon regeneration and
      remyelination, dendritic proliferation, activity-dependent adaptations, skills
      learning, and behavioral testing. Preclinical experiments that inform the design
      of human trials ideally include a lesion of etiology, volume and location that
      reflects the human disease; examine changes induced by injury and by repair
      procedures both near and remote from the lesion; distinguish between reactive
      molecular and histologic changes versus changes critical to repair cascades;
      employ explicit training paradigms for the reacquisition of testable skills;
      correlate morphologic and physiologic measures of repair with behavioral measures
      of task reacquisition; reproduce key results in more than one laboratory, in
      different strains or species of rodent, and in a larger mammal; and generalize
      the results across several disease models, such as axonal regeneration in a
      stroke and spinal cord injury platform. Collaborations between basic and clinical
      scientists in the development of translational animal models of injury and repair
      can propel experiments for ethical bench-to-bedside therapies to augment the
      rehabilitation of disabled patients.

PMID- 17514712
TI  - Nerve growth factor gene delivery: animal models to clinical trials.
AB  - Cell death is the final common pathway of cognitive decline in Alzheimer's
      disease (AD). Nervous system growth factors, or neurotrophic factors, are
      substances naturally produced in the nervous system that support neuronal
      survival during development and influence neuronal function throughout adulthood.
      Notably, in animal models, including primates, neurotrophic factors prevent
      neuronal death after injury and can reverse spontaneous neuronal atrophy in
      aging. Thus, neurotrophic factor therapy has the potential to prevent or reduce
      ongoing cell loss in disorders such as AD. The main challenge in clinical testing
      of neurotrophic factors has been their delivery to the brain in sufficient doses
      to impact cell function, while restricting their delivery to specific sites to
      prevent adverse effects from broad distribution. This article reviews progress in
      evaluating the therapeutic potential of growth factors, from early animal models
      to human clinical trials currently underway in AD.

PMID- 17514713
TI  - Combinatorial treatments for promoting axon regeneration in the CNS: strategies
      for overcoming inhibitory signals and activating neurons' intrinsic growth state.
AB  - In general, neurons in the mature mammalian central nervous system (CNS) are
      unable to regenerate injured axons, and neurons that remain uninjured are unable
      to form novel connections that might compensate for ones that have been lost. As
      a result of this, victims of CNS injury, stroke, or certain neurodegenerative
      diseases are unable to fully recover sensory, motor, cognitive, or autonomic
      functions. Regenerative failure is related to a host of inhibitory signals
      associated with the extracellular environment and with the generally low
      intrinsic potential of mature CNS neurons to regenerate. Most research to date
      has focused on extrinsic factors, particularly the identification of inhibitory
      proteins associated with myelin, the perineuronal net, glial cells, and the scar
      that forms at an injury site. However, attempts to overcome these inhibitors have
      resulted in relatively limited amounts of CNS regeneration. Using the optic nerve
      as a model system, we show that with appropriate stimulation, mature neurons can
      revert to an active growth state and that when this occurs, the effects of
      overcoming inhibitory signals are enhanced dramatically. Similar conclusions are
      emerging from studies in other systems, pointing to a need to consider
      combinatorial treatments in the clinical setting.

PMID- 17514714
TI  - RNA transport and localized protein synthesis in neurological disorders and
      neural repair.
AB  - Neural cells are able to finely tune gene expression through post-transcriptional
      mechanisms. Localization of mRNAs to subcellular regions has been detected in
      neurons, oligodendrocytes, and astrocytes providing these domains with a locally
      renewable source of proteins. Protein synthesis in dendrites has most frequently
      been associated with synaptic plasticity, while axonally synthesized proteins
      appear to facilitate pathfinding and injury responses. For oligodendrocytes,
      mRNAs encoding several proteins for myelin formation are locally generated
      suggesting that this mechanism assists in myelination. Astrocytic processes have
      not been well studied but localization of GFAP mRNA has been demonstrated. Both
      RNA transport and localized translation are regulated processes. RNA transport
      appears to be highly selective and, at least in part, the destiny of individual
      mRNAs is determined in the nucleus. RNA-protein and protein-protein interactions
      determine which mRNAs are targeted to subcellular regions. Several RNA binding
      proteins that drive mRNA localization have also been shown to repress translation
      during transport. Activity of the translational machinery is also regulated in
      distal neural cell processes. Clinically, disruption of mRNA localization and/or
      localized mRNA translation may contribute to pathophysiology of fragile X mental
      retardation and spinal muscular atrophy. Axonal injury has been shown to activate
      localized protein synthesis, providing both a means to initiate regeneration and
      retrogradely signal injury to the cell body. Decreased capacity to transport
      mRNAs and translational machinery into distal processes could jeopardize the
      ability to respond to injury or local stimuli within axons and dendrites.

PMID- 17514715
TI  - Navigating their way to the clinic: emerging roles for axon guidance molecules in
      neurological disorders and injury.
AB  - The mechanisms underlying formation of the basic network of the nervous system
      are of fundamental interest in developmental neurobiology. During the wiring of
      the nervous system, newborn neurons send axons that travel long distances to
      their targets. These axons are directed by environmental cues, known as guidance
      cues, to their correct destinations. Through extensive studies in vertebrates and
      invertebrates many of the guidance cues and their receptors have been identified.
      Recently, guidance molecules have been suggested to have important roles in
      pathological conditions of the nervous system. Mutations in guidance receptors
      have been associated with hereditary neurological disorders, and deregulation of
      guidance cues might be associated with predisposition to epilepsy. In addition,
      it was suggested that guidance molecules play roles in the ability of the adult
      nervous system to recover and repair after injury. Thus, molecules that were
      first discovered as "developmental cues" are now emerging as important factors in
      neurological disease and injury in the adult.

PMID- 17514716
TI  - Polyphosphoinositol lipids: under-PPInning synaptic function in health and
      disease.
AB  - Phosphoinositides (PPIn) form a unique family of lipids derived by
      phosphorylation of the parent compound, phosphatidylinositol. Despite being minor
      constituents of synaptic membranes, these lipids have exceptionally high rates of
      metabolic turnover and are involved with myriad aspects of pre- and post-synaptic
      function, from the control of the synaptic vesicle cycle to postsynaptic
      excitability. In this review, we outline the main synaptic processes known to be
      regulated by these molecules, focusing mainly but not exclusively on the major
      species phosphatidylinositol 4-phosphate and phosphatidylinositol (4,5)
      bisphosphate. Furthermore, we discuss the enzymes responsible for their synthesis
      and degradation, with a view to exploring how the activity-dependent control of
      their enzymatic action can lead to the precise regulation of PPIn levels at the
      nerve terminal. Also, the modulation of synaptic PPIn turnover by drugs used for
      the treatment of bipolar disorder is discussed. We propose that the modulation of
      PPIn levels may act as a central mechanism to coordinate the cascade of synaptic
      events leading to neurotransmission.

PMID- 17514717
TI  - Introduction: translating development - from bench to bedside with molecular
      neurobiology.

PMID- 17514718
TI  - Current concepts of the cellular and molecular pathophysiology of multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is the most common demyelinating disease. It poses many
      challenges both clinically and scientifically. Progress made in understanding the
      genetics, immunology, and neurobiology of MS to date has positioned the field for
      further breakthroughs both in understanding the etiology and pathogenesis as well
      as the development of rationally based therapeutics. This review will cover
      fundamental aspects of the clinical and pathologic features of MS. Identified
      genetic markers will be considered as well as the evolving understanding of
      immunologic and neurobiological aspects of the disease. The development of immune
      therapy based on this knowledge is already apparent and it is likely that
      neuroprotective therapies will evolve to complement immune modulation in treating
      the disease.

PMID- 17514719
TI  - Ovarian steroids and premenstrual symptoms: a comparison of group differences and
      intra-individual patterns.
AB  - To examine the relationship of gonadal hormone and symptom patterns across the
      menstrual cycle, women screened for 2-3 cycles completed an intensive study
      cycle; 26 had a low-severity symptoms (LS), 20, a premenstrual syndrome (PMS),
      and 26, a premenstrual magnification pattern (PMM). All completed daily symptom
      diaries and collected late afternoon urine samples which were assayed for
      pregnanediol and estradiol for that cycle. The PMS and PMM groups had
      significantly more positive cross-correlations of pregnanediol and symptoms than
      the LS group. Women in all groups had similar levels of estradiol and
      pregnanediol. Women with PMS and PMM patterns responded to progesterone
      differently than women with LS patterns: thus the former groups may not benefit
      from hormone therapies.

PMID- 17514720
TI  - High-density lipoprotein prevents organ damage in endotoxemia.
AB  - High-density lipoprotein (HDL) may decrease organ injury in sepsis. This study
      was designed using an animal model to mimic people who had a high HDL level and
      to test HDL effects on preventing organ damage in endotoxemia. Endotoxemia was
      induced by an infusion of lipopolysac-charide (LPS) after HDL or LDL
      administration. Levels of blood biochemical substances, nitrate/nitrite, and TNF
      alpha in sera were measured. Pathological examinations were performed 72 hours
      after LPS infusion. HDL decreased the endotoxin-induced elevation of AST, ALT,
      BUN, creatinine, LDH, CPK, nitrate/nitrite, and TNF-alpha. On histological
      examination, neutrophil infiltration was lower in the HDL group. HDL had a
      significant effect in preventing endotoxin-induced organ damage.

PMID- 17514721
TI  - Health-related quality of life of Chinese people with schizophrenia in Hong Kong
      and Taipei: a cross-sectional analysis.
AB  - Health-related quality of life is an important outcome indicator of mental
      health. We assessed the perception of health-related quality of life of persons
      with schizophrenia in Hong Kong and Taipei. In-person survey interviews were
      conducted using the Chinese World Health Organization Quality of Life Scale-
      Brief Version. A convenience sample was recruited from psychiatric outpatient
      departments: 176 from Hong Kong and 80 from Taipei. We found that both groups
      were significantly less satisfied with their psychological and social
      relationship domains compared to other domains. Poor mental health predicted poor
      perception of health-related quality of life. Schizophrenia has an impact on many
      aspects of a person's functioning. A rehabilitation model that takes into account
      symptoms, financial situation, family support, and social functioning is
      required.

PMID- 17514722
TI  - Flexibility along the neck of the ostrich (Struthio camelus) and consequences for
      the reconstruction of dinosaurs with extreme neck length.
AB  - The gross morphology and the flexibility along the neck of the ostrich (Struthio
      camelus) were examined using fresh tissue as well as neck skeletons. The results
      of the morphologic studies were compared with results from observations of living
      ostriches. The investigation was focused on differences in the morphology and the
      function between different sections of the neck. Additionally, the function of
      major dorsal neck ligaments was examined, including measurements of force-strain
      relations. Comparative studies of giraffes (Giraffa camelopardalis) and camels
      (Camelus bactrianus) were conducted to find relations between the flexibility
      along the neck and the general feeding strategy. The examinations revealed that
      the neck of the ostrich can be divided into four sections with different
      functions. The first is the atlas-axis-complex which is responsible for torsion.
      The adjacent cranial section of the neck is flexible in dorsoventral and lateral
      directions but this part of the neck is usually kept straight at rest and during
      feeding. Dorsoventral flexibility is highest in the middle section of the neck,
      whereas the base of the neck is primarily used for lateral excursions of the
      neck. For giraffes and camels, the posture and utilization of the neck are also
      reflected in the flexibility of the neck. For all three species, it is possible
      to reconstruct the pattern of flexibility of the neck by using the neck skeletons
      alone. Therefore, it appears reasonable to reconstruct the neck utilization and
      the feeding strategies of dinosaurs with long necks by deriving the flexibility
      of the neck from preserved vertebrae. For Diplodocus carnegii the neck posture
      and the feeding strategy were reconstructed. Two neck regions, one around the 9th
      neck vertebra and the second at the base of the neck, indicate that Diplodocus,
      like the ostrich, adopted different neck postures. The neck was probably kept
      very low during feeding. During interruptions of the feeding, e.g., in an alert,
      the head could have been lifted in an economic way by raising the cranial section
      of the neck. During standing and locomotion the head was probably located well
      above the shoulders.

PMID- 17514723
TI  - Three-dimensional fine structural reconstruction of the nose sensory structures
      of Acrobeles complexus compared to Caenorhabditis elegans (Nematoda: Rhabditida).
AB  - Nematode sensory structures can be divided into two classes; cuticular sensillae,
      with dendrites ending outside the epidermis, and internal receptors, that
      typically are single dendrites terminating within the body cavity. Fine structure
      of the former has been described completely in more than a dozen nematode taxa,
      while the latter were previously only well understood in the microbial feeder
      Caenorhabditis elegans. The distantly related nematode Acrobeles complexus has a
      similar ecology and together the two span a clade representing a large proportion
      of nematode biodiversity. The cuticular sensillae and internal receptors of A.
      complexus are here shown to be remarkably similar in number, arrangement, and
      morphology to those of C. elegans. Several key differences are reported that
      likely relate to function, and suggest that this nematode has a cuticular
      sensillum morphology that is closer to that of the common ancestor of the two
      taxa. Internal sensory receptors have more elaborate termini than those of C.
      elegans. The existence of a novel form of mechanoreceptor in A. complexus and
      spatial relationships between sensillum dendrites suggest differences between two
      classes of sensillae in how a touch-response behavior may be mediated.

PMID- 17514724
TI  - The influence of end-of-life cancer care on caregivers.
AB  - The purpose of this secondary analysis was to glean from prospective data whether
      those caring for elderly family members recently diagnosed with cancer who
      ultimately died reported different caregiver depressive symptomatology and burden
      than caregivers of those who survived. Findings from interviews with 618
      caregivers revealed that caregiver depressive symptomatology differed based on
      family members' survival status, and spousal caregivers experienced greater
      burden when a family member was near death than did non-spousal caregivers.
      Family member symptoms and limitations in daily living, as well as caregiver
      health status, age, and employment, were associated with caregiver depressive
      symptomatology and burden; however, these associations had no interaction with
      family member survival status.

PMID- 17514725
TI  - A comparison of research utilization among nurses working in Canadian civilian
      and United States Army healthcare settings.
AB  - Researchers and theorists working in the field of knowledge translation point to
      the importance of organizational context in influencing research utilization. The
      study purpose was to compare research utilization in two different healthcare
      contexts--Canadian civilian and United States (US) Army settings. Contrary to the
      investigators' expectations, research utilization scores were lower in US Army
      settings, after controlling for potential predictors. In-service attendance,
      library access, belief suspension, gender, and years of experience interacted
      significantly with the setting (military or civilian) for research utilization.
      Predictors of research utilization common to both settings were attitude and
      belief suspension. Predictors in the US Army setting were trust and years of
      experience, and in the Canadian civilian setting were in-service attendance, time
      (organizational), research champion, and library access. While context is of
      central importance, individual and organizational predictors interact with
      context in important although not well-understood ways, and should not be
      ignored.

PMID- 17514726
TI  - Supplementary breaks and stretching exercises for data entry operators: a follow
      up field study.
AB  - BACKGROUND: This study expanded previous NIOSH-IRS research examining the effects
      of rest breaks and stretching exercises on symptoms and performance in data-entry
      workers. METHODS: All workers spent 4 weeks with conventional breaks (two 15 min
      breaks per day) and 4 weeks with supplementary breaks (two 15 min breaks plus
      four 5 min breaks per day). One-half were assigned at random to a group
      instructed to perform brief stretching exercises during breaks. The remainder
      comprised the "no stretching" (control) group. RESULTS: 51 workers (stretch group
      n = 21; no stretch group n = 30) completed the study symptom questionnaires.
      Discomfort and eyestrain were significantly lower with supplementary breaks, and
      supplementary breaks attenuated accumulation of discomfort and eyestrain during
      work sessions. Data-entry speed was significantly faster with supplementary
      breaks so that work output was maintained, despite replacing 20 min of work time
      with break time. In the stretch group, workers reported stretching during only
      25% of conventional breaks and 39% of supplementary breaks, and no significant
      effects of stretching on discomfort or performance were observed. CONCLUSIONS:
      These results provide further converging evidence that supplementary breaks
      reliably minimize discomfort and eyestrain without impairing productivity. Low
      compliance in performing stretches prevented valid assessment of stretching
      effects. Further research on stretching exercises and exercise compliance is
      warranted.

PMID- 17514727
TI  - Solid state characterization of progesterone in a freeze dried 1:2
      progesterone/HPBCD mixture.
AB  - Progesterone rapidly dissolves in an aqueous solution containing hydroxypropyl
      beta-cyclodextrin (HPBCD) at 1:2 molar ratio, forming a soluble inclusion
      complex. After filtration and freeze-drying of the final solution, the final
      powder was examined by SEM, DSC, TGA, XRD, Raman, and FTIR spectroscopy.
      Experimental results confirm that an inclusion complex exists in the solid state
      and possible structure of the complex is briefly discussed.

PMID- 17514728
TI  - Enhanced osteolytic potential of monocytes/macrophages derived from bone marrow
      after particle stimulation.
AB  - BACKGROUND: Total hip replacement can be complicated by periprosthetic
      osteolysis. Monocytes/macrophages play a major role in the formation of the
      foreign body granulomas induced by wear debris. We hypothesized that
      periprosthetic monocytes/macrophages do not only accelerate inflammatory and
      osteoclast-mediated osteolytic processes, but also resorb periprosthetic bone
      directly by themselves. This study was designed to evaluate the osteolytic
      potential in vitro of monocytes/macrophages derived from bone marrow. METHODS:
      Monocytes/macrophages were produced by filtration of rat bone marrow cells,
      followed by culture in the presence of macrophage-colony stimulating factor (M
      CSF). Monocyte/macrophage properties were ascertained using immunocytochemistry
      and phagocytic activity. Osteolytic cytokines and extracellular matrix degrading
      proteinases were quantified at the mRNA level. RESULTS: Adherent cell fraction
      was immunoreactive for the monocyte/macrophage specific marker CD68 and active in
      the phagocytosis of carbon particles up to 72 h. They also showed
      immunoreactivity to cathepsin K, IL-1beta, IL-6, and M-CSF, but mostly did not
      react to TRAP. mRNA levels of osteolytic cytokines and extracellular matrix
      degrading proteinases were enhanced, but that of RANKL were not.
      Monocytes/macrophages resorbed dentine discs and carbonated calcium phosphate was
      very actively resorbed after stimulation with titanium particles. DISCUSSION:
      Harvested bone marrow cells expressed monocyte/macrophage phenotype, but not
      osteoclastic markers. The capacity of these cathepsin-K-positive phagocytic cells
      to resorb dentine discs and carbonated calcium phosphate in vitro suggests a
      direct role of monocytes/macrophages in bone resorption and periprosthetic
      osteolysis. The finding supports our hypothesis and previous histomorphometric
      observations on the presence of such osteolytic macrophages in vivo around
      loosening prosthesis.

PMID- 17514729
TI  - Current approaches for risk stratification of infectious complications in
      pediatric oncology.
AB  - Infections are serious complications of cytoreductive therapy in pediatric cancer
      patients presenting with febrile neutropenia. It is standard of care to initiate
      empirical intravenous broad-spectrum antibiotics until the fever and neutropenia
      resolve. However, it might be effective and safe to allow for early hospital
      discharge in certain subgroups of patients. Two strategies for risk
      stratification of pediatric cancer patients with regard to infectious
      complications are discussed in this review: (1) clinical risk parameters and
      laboratory measures to assist therapeutic management at presentation with fever
      in neutropenia, and (2) investigations of individual genetic susceptibility
      factors to tailor potential prophylactic approaches. Given the data available
      from a significant number of small studies, a large prospective non-inferiority
      trial is essential to assess low-risk clinical factors and additional laboratory
      or genetic markers for their predictive value.

PMID- 17514730
TI  - Are we finally ready for outpatient management of febrile neutropenia?

PMID- 17514731
TI  - A novel mutation in the NF1 gene in two siblings with neurofibromatosis type 1
      and bilateral optic pathway glioma.
AB  - We present the clinical and ophthalmological findings, genetic analysis, and
      therapy of two siblings with NF1 and bilateral OPG. In genetic analysis, a
      heteroduplex profile was detected in exon 4b of the NF1 gene for the affected
      patients and mother. Sequencing of the DNA samples identified a C > T nucleotide
      change in exon 4b (c484CAG > TAG). This nonsense mutation resulted in a change of
      glutamine to a stop codon (Q162X) and is a novel NF1 gene alteration.

PMID- 17514732
TI  - Liposomal amphotericin B prophylaxis of invasive mold infections in children post
      allogeneic stem cell transplantation.
AB  - BACKGROUND: Invasive mold infections (IMI) are a leading cause of infectious
      mortality in allogeneic stem cell transplant (AlloSCT) recipients. Fluconazole,
      the current standard for fungal prophylaxis, is ineffective against molds. We
      initiated a pilot study to determine the safety and activity of prophylactic
      liposomal amphotericin B (AMB) in preventing IMI in pediatric and adolescent
      AlloSCT recipients during the first 100 days. PROCEDURE: Fifty-one patients (57
      AlloSCT) were given AMB (3 mg/kg/day) intravenously, day 0-100. Median age 6
      years, 32 males, 19 females. Donors: 33 unrelated and 2 related cord blood, 13
      related and 1 unrelated peripheral blood stem cell and 8 related bone marrow
      (BM); 30 received myeloablative and 27 reduced intensity conditioning. Graft
      versus-host disease (GVHD) prophylaxis comprised tacrolimus and mycophenolate
      mofetil. RESULTS: Median follow-up is 557 days. AMB was generally well tolerated.
      The probability of developing >/=grade II acute GVHD and extensive chronic GVHD
      was 45% and 7%, respectively. Estimated 1-year OS is 62.4% for all patients with
      78.8% and 26.7% for average-risk and poor-risk, respectively. The incidence of
      IMI was 0%. CONCLUSIONS: These results suggest prophylactic AMB is tolerable and
      may prevent IMI, especially Aspergillus, during the first 100 days post AlloSCT
      in pediatric and adolescent patients. A randomized study is needed to determine
      the efficacy of this approach.

PMID- 17514733
TI  - Sperm banking for adolescent and young adult cancer patients: sperm quality,
      patient, and parent perspectives.
AB  - BACKGROUND: Infertility is often a complication for adolescent and young adult
      males who receive cancer therapy, a problem that might be averted through using
      cryopreserved sperm. We aim to evaluate feasibility of offering newly diagnosed
      patients the opportunity to bank sperm and, to determine the beliefs and decision
      making processes of patients and their parents who considered sperm banking.
      PROCEDURE: Eligible patients and parents were approached and offered sperm
      cryopreservation. Semen samples from patients who sequentially attempted sperm
      banking were analyzed. Questionnaires were then administered to patients and
      parents who had been approached about sperm banking. RESULTS: Semen samples from
      68 patients were analyzed. Nine patients were azoospermic; all had been pre
      treated with chemotherapy. Fifty patients completed the questionnaire. Parent and
      patient made the decision together to bank 80% of the time. All sons who
      attempted to bank and their parents felt they had made the right decision,
      including those who attempted but failed. CONCLUSIONS: Viable sperm can be
      collected successfully from adolescent and young adults who are newly diagnosed
      with cancer. Semen quality was dramatically reduced by one course of gonadotoxic
      therapy. Parents and patients want information regarding sperm cryopreservation
      early. Parents appear to play an important role in the decision to sperm bank. We
      recommend sperm banking be offered to all eligible patients.

PMID- 17514734
TI  - Correlation between asparaginase sensitivity and asparagine synthetase protein
      content, but not mRNA, in acute lymphoblastic leukemia cell lines.
AB  - BACKGROUND: Asparaginase (ASNase) is an essential component of most treatment
      protocols for childhood acute lymphoblastic leukemia (ALL). Although increased
      asparagine synthetase (ASNS) expression may contribute to ASNase resistance,
      there is conflicting data from patient samples with regard to correlation between
      ASNS mRNA content and ASNase sensitivity. PROCEDURE: Both T-cell and B-cell
      derived ALL cell lines were treated with ASNase and then monitored for cell
      proliferation, cell death, and ASNS mRNA and protein expression. RESULTS: Despite
      elevated ASNS mRNA following ASNase treatment, different ALL cell lines varied
      widely in translation to ASNS protein. Although ASNS mRNA levels did not
      consistently reflect ASNase sensitivity, there was an inverse correlation between
      ASNS protein and ASNase-induced cell death. Expression of ASNS in an ASNase
      sensitive cell line resulted in enhanced ASNase resistance, and conversely, siRNA
      mediated inhibition of ASNS expression promoted increased drug sensitivity.
      CONCLUSIONS: These observations provide an explanation for the ASNase sensitivity
      of ALL cells and demonstrate the importance of measuring ASNS protein rather than
      mRNA in predicting ASNase responsiveness.

PMID- 17514735
TI  - Is postal follow-up of childhood cancer survivors worthwhile?
AB  - BACKGROUND: Childhood cancer survival has increased over the last 30 years, but
      long-term effects necessitate continued monitoring of survivors. Since not all of
      them attend follow-up clinics, this study assesses the efficacy of obtaining
      information from general practitioners (GPs) through a 5-year rolling postal
      program. PROCEDURE: Survivors were included who had been diagnosed with a
      malignancy in the West Midlands since 1957 and were not attending central long
      term follow-up clinics. RESULTS: One thousand twenty-seven patients were followed
      up between 1993 and 2004. Replies were received on 903 (88% response). There were
      44 subsequent malignancies and 42 deaths. No medical problems were reported in
      341/935 patients (36.5%); in the other 594 endocrine effects were the most
      common, with visual effects the biggest single problem. Brain tumor survivors had
      the largest proportion of problems. CONCLUSIONS: The response rate and
      information quality achieved show that this method of follow-up is feasible, in
      cases of discharged or defaulting patients. These data will complement those
      derived from hospital-based follow-up studies, to give a broader understanding of
      the spectrum of late effects experienced by survivors and may inform the
      development of specific long-term follow-up protocols.

PMID- 17514736
TI  - Prognostic influence of minimal residual disease detected by flow cytometry and
      peripheral blood stem cell transplantation by CD34+ selection in childhood
      advanced neuroblastoma.
AB  - OBJECTIVE: To determine whether neuroblastoma (NB) minimal residual disease (MRD)
      in bone marrow (BM) detected by flow cytometry could predict prognosis and
      whether tumor cell purging by CD34(+) cell selection prior to transplantation
      will impact on disease-free survival. METHODS: NB MRD in BM was evaluated by flow
      cytometry with CD45-FITC-/CD81-PE+/CD56-PECy5+ monoclonal antibodies cocktail.
      Peripheral blood stem cell (PBSC) was enriched via positive CD34(+) cell
      selection by magnetic-activated cell separation system (MACS). RESULTS: Eleven of
      31 patients with CD45(-)/CD81+/CD56+ cells by flow cytometry at diagnosis became
      negative after an average of four courses of chemotherapy. All 11 patients
      remained alive without evidence of disease. Thirteen of the 20 patients with
      positive MRD relapsed and 1 patient died from disease (mean 25.8 months). There
      was a significant difference between these two groups. MRD in BM was tested
      before PBSC transplantation (PBSCT) for 19 NB patients. Fourteen was negative, 4
      of them relapsed and 10 patients remained alive without evidence of disease.
      Another 5 patients with positive MRD, all of them relapsed (mean 17 months after
      PBSCT) with a significant difference between these two groups. Fourteen of 19
      PBSC were purged with CD34(+) selection procedure. Six of 14 relapsed (mean 18.43
      months after PBSCT). Five patients did not purge for CD34(+) selection, and 3 of
      them relapsed with no significant difference between these two groups.
      CONCLUSIONS: Positive MRD in BM after an average of four courses of chemotherapy
      and before PBSCT is an unfavorable factor for stage IV NB. CD34(+) selection
      purging for PBSCT may not improve the prognosis for children with neuroblastoma
      in advanced stage.

PMID- 17514737
TI  - Uneventful administration of vincristine in Charcot-Marie-Tooth disease type 1X.
AB  - Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral
      neuropathy. Administration of vinca alkaloids is considered contraindicated in
      CMT because of the risk of life threatening acute neuropathy. We describe a 5
      year-old patient with a family history of X-linked CMT1 who presented with Wilms
      tumour. Despite confirmation of a connexin 32 point mutation, the patient was
      treated with 40.5 mg/m(2) of vincristine with no clinical evidence of drug
      related neuropathy. This case describes vincristine being safely administered to
      a patient with molecularly proven type CMT 1X, but in type 1A CMT vincristine is
      still contraindicated. An extensive literature review revealed no other series of
      cases in which vincristine administration in molecularly proven CMT 1X had been
      described. CMT should be excluded in any patient who develops a profound, acute
      neuropathy following vincristine, as many patients in the cases reviewed were
      asymptomatic prior to treatment.

PMID- 17514738
TI  - Pediatric thyroid cancer arising after treatment for pleuropulmonary blastoma.
AB  - A 3-year-old female presented with a large tumor occupying the right thoracic
      space. Open biopsy revealed the pathological diagnosis of pleuropulmonary
      blastoma. After the first-line chemotherapy, the patient underwent surgical
      resection, then two courses of high-dose chemotherapy. Three years later,
      follicular carcinoma of the right thyroid lobe was found, so a right
      hemithyroidectomy was performed. Five months later, the thyroid tumor recurred.
      The remaining thyroid lobe was completely excised and radioiodine therapy was
      administered. The patient has remained tumor-free for 3 years. The etiology and
      treatment of the uncommon combination of pleuropulmonary blastoma and thyroid
      carcinoma is discussed.

PMID- 17514739
TI  - Who will care for tomorrow's children with benign hematological conditions?

PMID- 17514740
TI  - Risk of thrombosis with anomalies of the inferior vena cava and factor V Leiden.

PMID- 17514741
TI  - Concerns about infertility risks among pediatric oncology patients and their
      parents.
AB  - BACKGROUND: Given pediatric cancer patients are living into adulthood, parents
      and patients need to be informed about fertility-related side effects of their
      particular treatment. PROCEDURE: We surveyed 97 parents of pediatric patients of
      all ages as well as 37 adolescent patients of 14 years or older who were
      presented for care at the Lucile Packard Children's Hospital (LPCH) at the
      Stanford University Medical Center. We estimated the potential infertility risk
      (low, intermediate, and high) based on the child's treatment regimen. RESULTS: In
      contrast to our hypothesis, the majority of parents in all three risk categories
      were concerned about fertility-related side effects of cancer treatment. Many
      parents with children at low risk were concerned (58.3%) whereas not all parents
      with children at intermediate or high risk were concerned, 61.5% and 73.3%
      respectively, P = 0.43. Indeed, over 50% of all parents were erroneously
      concerned that cancer therapies cause DNA damage to their child's eggs (or
      sperm). Only 29.9% of parents were satisfied with the amount of information
      received. Similar patterns were seen among the adolescent patient sample.
      CONCLUSIONS: Parents of pediatric cancer patients and teenage patients have
      concerns about fertility-related side effects regardless of treatment received.
      Targeted education about infertility risk before and after treatment can address
      these gaps.

PMID- 17514742
TI  - Acute stress in parents of children newly diagnosed with cancer.
AB  - OBJECTIVE: Acute Stress Disorder (ASD) and subclinical symptoms of acute stress
      (SAS) may be a useful framework for understanding the psychological reactions of
      mothers and fathers of children newly diagnosed with a pediatric malignancy.
      PATIENTS AND METHODS: Mothers (N = 129) and fathers (N = 72) of 138 children
      newly diagnosed with cancer completed questionnaires assessing acute distress,
      anxiety, and family functioning. Demographic data were also gathered. Inclusion
      criteria were: a confirmed diagnosis of a pediatric malignancy in a child under
      the age of 18 years without prior chronic or life threatening illness and fluency
      in English or Spanish. RESULTS: Descriptive statistics and multiple linear
      regressions were used to examine predictors of SAS. Fifty-one percent (N = 66) of
      mothers and 40% (N = 29) of fathers met DSM-IV diagnostic criteria for ASD. The
      majority of the sample reported experiencing at least one SAS. General anxiety,
      but not family functioning, was a strong predictor of SAS in both mothers and
      fathers even after controlling for demographic characteristics. CONCLUSIONS:
      Immediately following their child's diagnosis of cancer, most mothers and fathers
      experience SAS, with a subsample meeting criteria for ASD. More anxious parents
      are at heightened risk of more intense reactions. The findings support the need
      for evidence-based psychosocial support at diagnosis and throughout treatment for
      families who are at risk for acute distress reactions.

PMID- 17514743
TI  - Pentostatin, cyclophosphamide, and rituximab regimen in older patients with
      chronic lymphocytic leukemia.
AB  - BACKGROUND: The prevalence of chronic lymphocytic leukemia (CLL) increases with
      age. Although chemoimmunotherapy (CIT) has dramatically improved response rates
      in patients with CLL, some CIT regimens are not well tolerated by many patients
      >or=70 years of age. METHODS: Sixty-four previously untreated patients with CLL
      and serum creatinine <1.5 times the upper limit of normal who met National Cancer
      Institute (NCI) 96-WG criteria for treatment received pentostatin (2 mg/m(2)),
      cyclophosphamide (600 mg/m(2)), and rituximab (375 mg/m(2)). The authors measured
      performance status at study entry and used age, weight, and baseline creatinine
      to calculate creatinine clearance (CrCl). RESULTS: Eighteen of 64 (28%) patients
      were ages >or=70 years. Although individuals ages >or=70 years were more likely
      to have delayed treatment cycles (28% vs 7%; P=.03), there were no significant
      differences in the number of cycles administered, need for dose reductions, or
      grade 3-4 hematologic, infectious, or other toxicities. No significant
      differences in overall response rate, complete response rate, or progression-free
      survival were observed by age. Twenty-five (39%) patients had a CrCl < 70 mL/min
      (range, 34-67). Although individuals with CrCl < 70 were more likely to require
      dose reduction (24% vs 5%; P=.05), there were no significant differences in the
      number of cycles administered or grade 3-4 hematologic, infectious, or other
      toxicities. No significant difference in overall response rate, complete response
      rate, or progression-free survival were observed between patients with CrCl >or=
      70 mL/min and those with CrCl < 70 mL/min. CONCLUSIONS: In this clinical trial,
      the PCR regimen was well tolerated by older patients and individuals with CrCl
      <or= 70. The efficacy of PCR was not significantly affected by age or renal
      function. These findings suggest PCR may be a good therapeutic option for older
      patients and those with modestly decreased renal function.

PMID- 17514744
TI  - Role of GTPases in ribosome assembly.
AB  - GTPases are a universally conserved class of regulatory proteins involved in such
      diverse cellular functions as signal transduction, translation, cytoskeleton
      formation, and intracellular transport. GTPases are also required for ribosome
      assembly in eukaryotes and bacteria, where they present themselves as possible
      regulatory molecules. Strikingly, in bacteria they represent the largest class of
      essential assembly factors. A review of their common structural, biochemical and
      genetic interactions is presented and integrated with models for their function
      in ribosome assembly.

PMID- 17514745
TI  - Injectable, in situ forming poly(propylene fumarate)-based ocular drug delivery
      systems.
AB  - This study sought to develop an injectable formulation for long-term ocular
      delivery of fluocinolone acetonide (FA) by dissolving the anti-inflammatory drug
      and the biodegradable polymer poly(propylene fumarate) (PPF) in the
      biocompatible, water-miscible, organic solvent N-methyl-2-pyrrolidone (NMP). Upon
      injection of the solution into an aqueous environment, a FA-loaded PPF matrix is
      precipitated in situ through the diffusion/extraction of NMP into surrounding
      aqueous fluids. Fabrication of the matrices and in vitro release studies were
      performed in phosphate buffered saline at 37 degrees C. Drug loadings up to 5%
      were achieved. High performance liquid chromatography was employed to determine
      the released amount of FA. The effects of drug loading, PPF content of the
      injectable formulation, and additional photo-crosslinking of the matrix surface
      were investigated. Overall, FA release was sustained in vitro over up to 400
      days. After an initial burst release of 22 to 68% of initial FA loading,
      controlled drug release driven by diffusion and bulk erosion was observed. Drug
      release rates in a therapeutic range were demonstrated. Release kinetics were
      found to be dependent on drug loading, formulation PPF content, and extent of
      surface crosslinking. The results suggest that injectable, in situ formed PPF
      matrices are promising candidates for the formulation of long-term, controlled
      delivery devices for intraocular drug delivery.

PMID- 17514746
TI  - Another "Awakenings".

PMID- 17514747
TI  - Re: safety of endobronchial biopsy in children with cystic fibrosis.

PMID- 17514748
TI  - Pulse oximetry coupled with spirometry in the emergency department helps
      differentiate an asthma exacerbation from possible vocal cord dysfunction.
AB  - PURPOSE: Spirometry performed by adolescents with refractory wheeze or stridor
      and respiratory distress, with normal room air oxygen saturation, may
      differentiate subjects not having an acute asthma exacerbation (AE-) from those
      who are (AE+). A subpopulation may also be identified that has flow volume loop
      (FVL) patterns consistent with vocal cord dysfunction (VCD). METHODS: Spirometry
      was performed by adolescents who presented to a pediatric emergency department
      (ED) with respiratory distress attributed to an acute AE who, after therapy, were
      still symptomatic and had room air oxygen saturation > or = 97%. Spirometry
      findings were classified as: (a) consistent with an acute AE, (b) variable
      extrathoracic airway obstruction pattern consistent with VCD, (c) a combination
      of the two, or (d) normal airflow. RESULTS: Of 2,073 adolescent visits for asthma
      seen in the ED in 2005, 20 encounters among 17 adolescents were examined during
      the period of 0700-2200 on weekdays when an investigator was available, of which,
      15 encounters were classified as AE-. In the AE- group, nine had FVL evidence of
      variable extrathoracic airway obstruction consistent with VCD, and six had normal
      spirometry. Three of the five encounters that were AE+ had FVL evidence
      consistent with VCD. CONCLUSIONS: Spirometry, performed on therapy-resistant
      wheezing or stridorous adolescent patients in respiratory distress with oxygen
      saturation > or =97%, may help differentiate patients who are not having an acute
      AE from those who are. In those subjects not having an acute AE, respiratory
      distress may prove to be due to VCD.

PMID- 17514749
TI  - Association analysis of MAPT H1 haplotype and subhaplotypes in Parkinson's
      disease.
AB  - OBJECTIVE: An inversion polymorphism of approximately 900 kb on chromosome 17q21,
      which includes the microtubule-associated protein tau (MAPT) gene defines two
      haplotype clades, H1 and H2. Several small case-control studies have observed a
      marginally significant excess of the H1/H1 diplotype among patients with
      Parkinson's disease (PD), and one reported refining the association to a region
      spanning exons 1 to 4 of MAPT. We sought to replicate these findings. METHODS: We
      genotyped 1,762 PD patients and 2,010 control subjects for a single nucleotide
      polymorphism (SNP) that differentiates the H1 and H2 clades. We also analyzed
      four SNPs that define subhaplotypes within H1 previously reported to associate
      with PD or other neurodegenerative disorders. RESULTS: After adjusting for age,
      sex, and site, we observed a robust association between the H1/H1 diplotype and
      PD risk (odds ratio for H1/H1 vs H1/H2 and H2/H2, 1.46; 95% confidence interval,
      1.25-1.69; p = 8 x 10(-7)). The effect was evident in both familial and sporadic
      subgroups, men and women, and early- and late-onset disease. Within H1/H1
      individuals, there was no significant difference between cases and control
      subjects in the overall frequency distribution of H1 subhaplotypes.
      INTERPRETATION: Our data provide strong evidence that the H1 clade, which
      contains MAPT and several other genes, is a risk factor for PD. However,
      attributing this finding to variants within a specific region of MAPT is
      premature. Thorough fine-mapping of the H1 clade in large numbers of individuals
      is now needed to identify the underlying functional variant(s) that alter
      susceptibility for PD.

PMID- 17514750
TI  - Anti-apoptotic genes Aven and E1B-19K enhance performance of BHK cells engineered
      to express recombinant factor VIII in batch and low perfusion cell culture.
AB  - The engineering of production cell lines to express anti-apoptotic genes has been
      pursued in recent years due to potential process benefits, including enhanced
      cell survival, increased protein expression, and improved product quality. In
      this study, a baby hamster kidney cell line secreting recombinant factor VIII
      (BHK-FVIII) was engineered to express the anti-apoptotic genes Aven and E1B-19K.
      In high cell density shake flask culture evaluation, 11 clonal cell lines
      expressing either E1B-19K or a combination of Aven and E1B-19K showed improved
      survival compared to both parental and blank vector cell line controls. These
      cell lines exhibited lower caspase-3 activation and reduced Annexin-V binding
      compared to the controls. Parental and blank vector cell lines were less than 50%
      viable after 48 h of exposure to thapsigargin while cell lines expressing E1B-19K
      with or without Aven maintained viabilities approaching 90%. Subsequently, the
      best Aven-E1B-19K candidate cell line was compared to the parental cell line in
      12-L perfusion bioreactor studies. Choosing the appropriate perfusion rates in
      bioreactors is a bioprocess optimization issue, so the bioreactors were operated
      at sequentially lower specific perfusion rates, while maintaining a cell density
      of 2 x 10(7) viable cells/mL. The viability of the parental cell line declined
      from nearly 100% at a perfusion rate of 0.5 nL/cell/day to below 80% viability,
      with caspase-3 activity exceeding 15%, at its lower perfusion limit of 0.15
      nL/cell/day. In contrast, the Aven-E1B-19K cell line maintained an average
      viability of 94% and a maximum caspase-3 activity of 2.5% even when subjected to
      a lower perfusion minimum of 0.1 nL/cell/day. Factor VIII productivity, specific
      growth rate, and cell size decreased for both cell lines at lower perfusion
      rates, but the drop in all cases was larger for the parental cell line. Specific
      consumption of glucose and glutamine and production of lactate were consistently
      lower for the Aven-E1B-19K culture. Furthermore, the yield of ammonia from
      glutamine increased for the Aven-E1B-19K cell line relative to the parent to
      suggest altered metabolic pathways following anti-apoptosis engineering. These
      results demonstrate that expression of anti-apoptotic genes Aven and E1B-19K can
      increase the stability and robustness of an industrially relevant BHK-FVIII
      mammalian cell line over a wide range of perfusion rates.

PMID- 17514751
TI  - Carbon metabolism and product inhibition determine the epoxidation efficiency of
      solvent-tolerant Pseudomonas sp. strain VLB120DeltaC.
AB  - Utilization of solvent tolerant bacteria as biocatalysts has been suggested to
      enable or improve bioprocesses for the production of toxic compounds. Here, we
      studied the relevance of solvent (product) tolerance and inhibition, carbon
      metabolism, and the stability of biocatalytic activity in such a bioprocess.
      Styrene degrading Pseudomonas sp. strain VLB120 is shown to be solvent tolerant
      and was engineered to produce enantiopure (S)-styrene oxide from styrene. Whereas
      glucose as sole source for carbon and energy allowed efficient styrene
      epoxidation at rates up to 97 micromol/min/(g cell dry weight), citrate was found
      to repress epoxidation by the engineered Pseudomonas sp. strain VLB120DeltaC
      emphasizing that carbon source selection and control is critical. In comparison
      to recombinant Escherichia coli, the VLB120DeltaC-strain tolerated higher toxic
      product levels but showed less stable activities during fed-batch cultivation in
      a two-liquid phase system. Epoxidation activities of the VLB120DeltaC-strain
      decreased at product concentrations above 130 mM in the organic phase. During
      continuous two-liquid phase cultivations at organic-phase product concentrations
      of up to 85 mM, the VLB120DeltaC-strain showed stable activities and, as compared
      to recombinant E. coli, a more efficient glucose metabolism resulting in a 22%
      higher volumetric productivity. Kinetic analyses indicated that activities were
      limited by the styrene concentration and not by other factors such as NADH
      availability or catabolite repression. In conclusion, the stability of activity
      of the solvent tolerant VLB120DeltaC-strain can be considered critical at
      elevated toxic product levels, whereas the efficient carbon and energy metabolism
      of this Pseudomonas strain augurs well for productive continuous processing.

PMID- 17514752
TI  - A method for lipase co-precipitation in a biodegradable protein matrix.
AB  - This article presents a novel method for immobilization of active ingredients.
      The method is based on CO(2) aided active ingredient co-precipitation with
      glycinin, a biodegradable protein matrix from edible soybean protein. Glycinin
      precipitates abundantly under isoelectric conditions and serves as the matrix
      within which the active substance is trapped during the precipitation process.
      The enzyme lipase from Candida rugosa was successfully co-precipitated into the
      protein pellet to prove the principle. It was shown that the lipase within the co
      precipitate retained lipase and esterase activity under different pH conditions.
      In some cases the activity was even higher than the activity of crude lipase,
      possibly due to the protective role of the matrix protein. Due to the retained
      lipase activity and food-grade quality of the binary precipitate, it has
      potential of being used in the food or pharmaceutical industry. Additional
      quality of the binary precipitate is the potentially significantly reduced
      downstream processing due to the fact that no organic solvents or precipitants
      were used in the precipitation process.

PMID- 17514753
TI  - Ultrasound enhanced glucose release from corn in ethanol plants.
AB  - This work evaluated the use of high power ultrasonic energy to treat corn slurry
      in dry corn milling ethanol plants to enhance liquefaction and saccharification
      for ethanol production. Corn slurry samples obtained before and after jet cooking
      were subjected to ultrasonic pretreatment for 20 and 40 s at amplitudes of
      vibration ranging from 180 to 299 microm(pp) (peak to peak amplitude in microm).
      The resulting samples were then exposed to enzymes (alpha-amylase and
      glucoamylase) to convert cornstarch into glucose. A comparison of scanning
      electron micrographs of raw and sonicated samples showed the development of
      micropores and the disruption of cell walls in corn mash. The corn particle size
      declined nearly 20-fold following ultrasonic treatment at high power settings.
      The glucose release rate from sonicated samples increased as much as threefold
      compared to the control group. The efficiency of ultrasound exceeded 100% in
      terms of energy gain from the sugar released over the ultrasonic energy supplied.
      Enzymatic activity was enhanced when the corn slurry was sonicated with
      simultaneous addition of enzymes. This finding suggests that the ultrasonic
      energy did not degrade or denature the enzymes during the pretreatment.

PMID- 17514754
TI  - Effect of sparger design on hydrodynamics of a gas recirculation anaerobic
      bioreactor.
AB  - The effects of sparger design and gas flow rate on, gas holdup distribution and
      liquid (slurry) recirculation velocity have been studied in a surrogate anaerobic
      bioreactor used for treating bovine waste with a conical bottom mixed by gas
      recirculation. A single orifice sparger (SOS) and a multi-orifice ring sparger
      (MORS) with the same orifice open area and gas flow rates (hence the same process
      power input) are compared in this study. The advanced non-invasive techniques of
      computer automated tomography (CT) and computer automated radioactive particle
      tracking (CARPT) were employed to determine gas holdup, liquid recirculation
      velocity, and the poorly mixed zones. Gas flows (Q(g)) ranging of 0.017 x 10(-3)
      m(3)/s to 0.083 x 10(-3) m(3)/s were used which correspond to draft tube
      superficial gas velocities ranging from 1.46 x 10(-2) m/s to 7.35 x 10(-2) m/s
      (based on draft tube diameter). Air was used for the gas, as the molecular
      weights of air and biogas (consisting mainly of CH(4) and CO(2)) are in the same
      range (biogas: 28.32-26.08 kg/kmol and air: 28.58 kg/kmol). When compared to the
      SOS for a given gas flow rate, the MORS gave better gas holdup distribution in
      the draft tube, enhanced the liquid (slurry) recirculation, and reduced the
      fraction of the poorly mixed zones. The improved gas holdup distribution in the
      draft tube was found to have increased the overall liquid velocity. Hence, for
      the same process power input the MORS system performed better by enhancing the
      liquid recirculation and reducing the poorly mixed zones.

PMID- 17514755
TI  - Characterizing the biochemical activity of full-scale enhanced biological
      phosphorus removal systems: A comparison with metabolic models.
AB  - The metabolism of polyphosphate accumulating organisms (PAOs) has been widely
      studied through the use of lab-scale enrichments. Various metabolic models have
      been formulated, based on the results from lab-scale experiments using enriched
      PAO cultures. A comparison between the anaerobic stoichiometry predicted by
      metabolic models with that exhibited by full-scale sludge in enhanced biological
      phosphorus removal (EBPR) wastewater treatment plants (WWTPs) was performed in
      this study. Batch experiments were carried out with either acetate or propionate
      as the sole carbon source, using sludges from two different EBPR-WWTPs in
      Australia that achieved different phosphorus removal performances. The results
      support the hypothesis that the anaerobic degradation of glycogen is the primary
      source of reducing equivalents generated by PAOs, however, they also suggested a
      partial contribution of the tricarboxylic acid (TCA) cycle in some cases. The
      experimental results obtained when acetate was the carbon source suggest the
      involvement of the modified succinate-propionate pathway for the generation of
      poly-beta-hydroxyvalerate (PHV). Overall, the batch test results obtained from
      full-scale EBPR sludge with both substrates were generally well described by
      metabolic model predictions for PAOs.

PMID- 17514756
TI  - Investigation of spacer length effect on immobilized Escherichia coli pili
      antibody molecular recognition by AFM.
AB  - The immobilization of antibodies to sensor surfaces is critical in biochemical
      sensor development. In this study, Poly(ethylene glycol) (PEG) and Jeffamine
      spacers were employed to tether Escherichia coli K99 pilus antibody to silicon
      wafer surfaces for the purpose of improving the orientation of antibody as well
      as reducing the steric hindrance. To illustrate the effect of spacer length, a
      variety of linear polymers were used to covalently attach the antibodies to
      silicon surfaces. Atomic Force Microscopy (AFM) and X-ray photoelectron
      spectroscopy (XPS) were used to characterize the surface morphology and chemical
      composition at each reaction step. The effect of spacer length in improving the
      specificity of immobilized antibody was investigated by attaching E. coli on the
      end of an AFM tip. The distribution of unbinding force and rupture distance from
      the force-distance curves obtained by AFM showed that the introduction of PEG
      spacer facilitates bacterial recognition which can improve the incidence of
      interactions by up to 90%. J600 proved to be the most effective spacer overcoming
      the steric hindrance seen with direct immobilization of antibody. In addition,
      the force spectroscopy reveals the elementary force quantum of E. coli-antibody
      to be 0.3 nN.

PMID- 17514757
TI  - In vitro study of using calcium phosphate cement as immunoisolative device to
      enclose insulinoma/agarose microspheres as bioartificial pancreas.
AB  - In this study, the feasibility of using calcium phosphate cement (CPC) as
      immunoisolative device to enclose insulinoma/agarose microspheres as
      bioartificial pancreas was evaluated. We fabricated a chamber by CPC and utilized
      X-ray diffraction, Scanning electron microscope and Mercury intrusion porosimetry
      to identify the characters of the CPC chamber. The nominal molecular weight cut
      off and cytotoxicity of CPC chamber were also evaluated. An insulinoma cell line
      (RIN-m5F) was chosen as insulin source and encapsulated in agarose microspheres
      and then enclosed in preformed CPC chamber. Insulin secretion was analyzed by
      Enzyme-linked immunosorbant assay to evaluate the function of insulinoma enclosed
      in CPC chamber. Results showed that the CPC chamber was non-cytotoxicity to
      insulinoma and can block the penetration of molecules which molecular weight
      larger than 12.4 kDa. Insulinoma inside the CPC chamber can secrete insulin in
      stable level for 30 days. This study indicated that we may use CPC as
      immunoisolative material to enclose insulinoma/agarose microspheres as
      bioartificial pancreas.

PMID- 17514758
TI  - A general kinetic model for biological nutrient removal activated sludge systems:
      model evaluation.
AB  - Hu et al. (2007) presented a general kinetic model for biological nutrient
      removal (BNR) activated sludge (AS) systems in general, but for external
      nitrification (EN) BNRAS (ENBNRAS) systems in particular. In this article, this
      model is evaluated against a large number of experimental data sets. In this
      evaluation, the model is first used to simulate a wide variety of conventional
      internal nitrification (IN) BNRAS systems to evaluate its predictions and also
      evaluate the model parameters suggested by Hu et al. (2007), and to calibrate
      those constants for which values are not available in the literature. Simulation
      results indicate that the model, with appropriately calibrated parameters, is
      capable of predicting COD removal, nitrification and denitrification and two
      types of biological excess phosphorus removal (BEPR), namely aerobic and
      anoxic/aerobic P uptake BEPR. The model is then used to simulate the ENBNRAS
      systems to evaluate its capacity of simulating the behaviour of this system.
      Simulation results show that the model is capable of simulating the behaviour of
      the ENBNRAS systems, including COD, nitrification, denitrification and BEPR,
      particularly anoxic P uptake BEPR, with the values of kinetic and stoichiometric
      parameters obtained in modelling conventional BNRAS systems, except for
      micro(NIT), K(MP), eta(PAO) and eta(H) which required calibration.

PMID- 17514759
TI  - An automated front-end monitor for anthrax surveillance systems based on the
      rapid detection of airborne endospores.
AB  - A fully automated anthrax smoke detector (ASD) has been developed and tested. The
      ASD is intended to serve as a cost effective front-end monitor for anthrax
      surveillance systems. The principle of operation is based on measuring airborne
      endospore concentrations, where a sharp concentration increase signals an anthrax
      attack. The ASD features an air sampler, a thermal lysis unit, a syringe pump, a
      time-gated spectrometer, and endospore detection chemistry comprised of
      dipicolinic acid (DPA)-triggered terbium ion (Tb(3+)) luminescence. Anthrax
      attacks were simulated using aerosolized Bacillus atrophaeus spores in fumed
      silica, and corresponding Tb-DPA intensities were monitored as a function of time
      and correlated to the number of airborne endospores collected. A concentration
      dependence of 10(2)-10(6) spores/mg of fumed silica yielded a dynamic range of 4
      orders of magnitude and a limit of detection of 16 spores/L when 250 L of air
      were sampled. Simulated attacks were detected in less than 15 min.

PMID- 17514760
TI  - A general kinetic model for biological nutrient removal activated sludge systems:
      model development.
AB  - In this article, a kinetic model is developed and presented for biological
      nutrient removal (BNR) activated sludge (BNRAS) systems in general, but for
      external nitrification (EN) BNRAS (ENBNRAS) systems in particular. The model is
      based on the UCTPHO model, but includes some significant modifications, such as
      anoxic P uptake and associated denitrification by phosphorus accumulating
      organisms (PAOs). Some key features of the model are described and discussed
      before the model is presented. Model evaluation will be addressed in another
      article (Hu et al., 2007).

PMID- 17514761
TI  - Total biosynthesis of deoxynucleoside triphosphates using deoxynucleoside
      monophosphate kinases for PCR application.
AB  - Polymerase chain reaction (PCR) and other PCR applications for DNA synthesis
      require deoxynucleoside triphosphates (dNTP) as the essential precursors and
      substrates. Currently, the dNTP is commercially produced by a chemical method
      which is environmentally hazardous and costly due to its low yields in both the
      synthetic reaction and purification processes. In this study, a enzyme technology
      for the total integrated biosynthesis of all dNTP components is presented. The
      bioprocess technology developed and reported here involves two sequential
      enzymatic phosphorylation reactions coupled with the cofactor regeneration
      starting from deoxynucleoside monophosphates (dNMP) to deoxynucleoside
      diphosphates (dNDP) in the first reaction step and to dNTP in the second reaction
      step in the same bioreactor. The four genes encoding these deoxynucleoside
      monophosphate kinases were cloned into the recombinant E. coli and expressed
      using the recombinant E. coli strains. The reaction mechanisms and kinetics of
      the four kinase enzymes are studied and reported. The total enzymatic syntheses
      of the four dNTP products were carried out in four separate operations under the
      high substrate concentrations which emulate the practical application. The
      optimal process conditions were carefully investigated and complete conversion of
      dNMP to dNTP at high substrate concentration have been achieved. The purity and
      quality of dNTP products obtained from this work were analyzed and found to be at
      least equivalent or better than the commercially available dNTP products. The PCR
      application of dNTP products obtained from this work were also evaluated for
      isolating and amplifying genes of different sizes from different organisms. The
      PCR performance test also showed an equivalent quality as compared to the
      commercially available dNTP. The bioprocess technology developed and reported
      here for production of dNTP will provide economically competitive and
      environmentally friendly viable technology for the industry and research
      community as compared to the chemical technology currently in use.

PMID- 17514762
TI  - Age- and site-specific decline in insulin-like growth factor-I receptor
      expression is correlated with differential growth plate activity in the mouse
      hindlimb.
AB  - The proximal and distal growth plates of the principal long bones do not
      contribute equally to longitudinal growth. Most forelimb elongation occurs at the
      shoulder and wrist, while most hindlimb growth occurs at the knee. This study
      examined whether insulin-like growth factor-I (IGF-I), a potent growth regulator,
      could underlie this variation via differential receptor expression. The
      spatiotemporal distribution of the IGF-I receptor (IGF-IR) was mapped in hindlimb
      growth plates (overall and within regional zones) from immature mice using
      immunohistochemistry. Growth activity was assessed by size/morphology of the
      growth plate and proliferating cell nuclear antigen (PCNA) expression. Both IGF
      IR and PCNA staining declined considerably with age in the proximal femur and
      distal tibia (hip and ankle), but expression remained high in the more active
      distal femur and proximal tibia (knee) throughout growth. Growth plate size
      decreased with age in all sites, but the absolute and relative decline in IGF-IR
      in the hips and ankles of older mice indicated a site-specific loss of IGF-I
      sensitivity in these less active regions. These results suggest that regulation
      of the IGF-IR may at least partially mediate differential long bone growth,
      thereby providing a local mechanism for altering skeletal proportions absent
      modification of systemic hormone levels.

PMID- 17514763
TI  - Study of the vasculature of the caprine reproductive organs using the tissue
      clearing technique, with special reference to the angioarchitecture of the utero
      ovarian vessels and the adaptation of the ovarian and/or vaginal arteries to
      multiple pregnancies.
AB  - Arteries of the reproductive tracts of nonpregnant does and does at 4, 7, 10, 13,
      16, and 18 weeks of gestation were injected in situ with Microfil. The tracts
      were fixed, dehydrated, and rendered transparent to reveal the paths of arteries.
      The tortuous ovarian artery lay in close apposition to the uterine tributary of
      the ovarian vein, an arrangement that may serve as a local utero-ovarian pathway
      for the corpus luteum (CL) luteolysis at the end of nonfertile estrous cycle.
      During pregnancy, this arteriovenous arrangement might transfer luteotropic
      substances from uterus to ovary, which might serve in maternal recognition of
      pregnancy and fit the fact that the goat is CL-dependent throughout gestation. In
      some cases of triplets, the size of the uterine branch of the ovarian artery was
      equal to or even larger than that of its parent artery and/or the ipsilateral
      uterine artery, and the vaginal artery contributed a connecting branch to the
      uterine artery. These physiological adaptations of the ovarian and/or vaginal
      arteries, which have not previously been described, correlate well with the
      increasing nutrient demands of the growing multiple fetuses.

PMID- 17514764
TI  - c-fos gene expression is increased in the paraventricular hypothalamic nucleus of
      Sprague-Dawley rats with visceral pain induced by acetic acid without detectable
      changes of corticotrophin-releasing factor mRNA: a quantitative approach with an
      image analysis system.
AB  - This study is the first of its kind to demonstrate that c-Fos immunoreactivity
      (ir) together with c-fos mRNA in their immediately adjacent tissue sections of a
      discrete brain region can be reliably measured. The c-fos gene expression in the
      paraventricular hypothalamic nucleus (PVN) of Sprague-Dawley rats for an animal
      model for visceral or somatovisceral pain induced by 2% acetic acid (AA) was used
      in this study. Specifically, c-fos mRNA signals were measured by quantitative
      autoradiography after in situ hybridization using c-fos oligodeoxynucleotide
      probe, and c-Fos-ir signals were represented by c-Fos immunostaining, as detected
      using c-Fos antibody in a regular immunohistochemistry. Signals from both c-Fos
      ir and c-fos mRNA in the PVN were measured from their immediately adjacent
      cryostat sections. For the measurement of c-Fos-ir, it was carried out by reading
      10 rectangles (1,000 microm(2)/rectangle) on each PVN section with c-Fos
      immunostaining. Specific signals were obtained from subtracting the nonspecific
      background signal from the total signals using a computer-assisted image analysis
      system. Results indicated that the AA treatment induced a significant increase of
      both c-Fos-ir and c-fos mRNA in the PVN. Interestingly, there was no increase of
      corticotrophin-releasing factor (CRF) mRNA expression in the PVN and central
      nucleus of the amygdala of Sprague-Dawley rats subjected to the AA treatment. In
      summary, this study has demonstrated that c-Fos-ir in the PVN with an anatomical
      resolution can be semiquantitatively measured after immunohistochemistry using an
      image analysis system, and that increased c-fos mRNA in the PVN 1 hr after the AA
      treatment is associated with no changes of the CRF mRNA expression.

PMID- 17514765
TI  - Microstructure of trabecular bone in a mouse model for Down syndrome.
AB  - Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21) and
      results in a suite of dysmorphic phenotypes, including effects on the postcranial
      skeleton and the skull. We have previously demonstrated parallels in the patterns
      of craniofacial dysmorphology in DS and in the Ts65Dn mouse model for DS. The
      specific mechanisms underlying the production of these changes in craniofacial
      shape remain unknown. High-resolution computed tomography scan data were
      collected for the presphenoid bone of euploid and aneuploid mice. Three
      dimensional morphometric parameters of trabecular bone were quantified and
      compared between euploid and aneuploid mice using nonparametric statistical
      tests. Aneuploid presphenoid bones were smaller than those of their euploid
      littermates and had lower bone volume fraction and fewer, more rod-like
      trabeculae. The differences in cancellous bone structure suggest that bone
      development, perhaps including bone modeling and remodeling, is affected by
      aneuploidy. These differences may contribute to the observed dysmorphology of
      skull and postcranial skeletal phenotypes in DS.

PMID- 17514766
TI  - Nonhuman anthropoid primate femoral neck trabecular architecture and its
      relationship to locomotor mode.
AB  - Functional analyses of human and nonhuman anthropoid primate femoral neck
      structure have largely ignored the trabecular bone. We tested hypotheses
      regarding differences in the relative distribution and structural anisotropy of
      trabecular bone in the femoral neck of quadrupedal and climbing/suspensory
      anthropoids. We used high-resolution X-ray computed tomography to analyze
      quantitatively the femoral neck trabecular structure of Ateles geoffroyi,
      Symphalangus syndactylus, Alouatta seniculus, Colobus guereza, Macaca
      fascicularis, and Papio cynocephalus (n = 46). We analyzed a size-scaled superior
      and inferior volume of interest (VOI) in the femoral neck. The ratio of the
      superior to inferior VOI bone volume fraction indicated that the distribution of
      trabecular bone was inferiorly skewed in most (but not all) quadrupeds and evenly
      distributed the climbing/suspensory species, but interspecific comparisons
      indicated that all taxa overlapped in these measurements. Degree of anisotropy
      values were generally higher in the inferior VOI of all species and the results
      for the two climbing/suspensory taxa, A. geoffroyi (1.71 +/- 0.30) and S.
      syndactylus (1.55 +/- 0.04), were similar to the results for the quadrupedal
      anthropoids, C. guereza (male = 1.64 +/- 0.13; female = 1.68 +/- 0.07) and P.
      cynocephalus (1.47 +/- 0.13). These results suggest strong trabecular
      architecture similarity across body sizes, anthropoid phylogenetic backgrounds,
      and locomotor mode. This structural similarity might be explained by greater
      similarity in anthropoid hip joint loading mechanics than previously considered.
      It is likely that our current models of anthropoid hip joint mechanics are overly
      simplistic.

PMID- 17514767
TI  - Characterization of nanostructured surfaces generated by reconstitution of the
      porin MspA from Mycobacterium smegmatis.
AB  - Nanostructures with long-term stability at the surface of gold electrodes are
      generated by reconstituting the porin MspA from Mycobacterium smegmatis into a
      specially designed monolayer of long-chain lipid surfactant on gold. Tailored
      surface coverage of gold electrodes with long-chain surfactants is achieved by
      electrochemically assisted deposition of organic thiosulfates (Bunte salts). The
      subsequent reconstitution of the octameric-pore MspA is guided by its
      extraordinary self-assembling properties. Importantly, electrochemical reduction
      of copper(II) yields copper nanoparticles within the MspA nanopores.
      Electrochemical impedance spectroscopy, reflection electron microscopy, and
      atomic force microscopy (AFM) show that: 1) the MspA pores within the self
      assembled monolayer (SAM) are monodisperse and electrochemically active, 2) MspA
      reconstitutes in SAMs and with a 10-nm thickness, 3) AFM is a suitable method to
      detect pores within SAMs, and 4) the electrochemical reduction of Cu2+ to Cu0
      under overpotential conditions starts within the MspA pores.

PMID- 17514768
TI  - Nonaligned carbon nanotubes anchored on porous alumina: formation, process
      modeling, gas-phase analysis, and field-emission properties.
AB  - We have developed a chemical vapor deposition (CVD) process for the catalytic
      growth of carbon nanotubes (CNTs), anchored in a comose-type structure on top of
      porous alumina substrates. The mass-flow conditions of precursor and carrier
      gases and temperature distributions in the CVD reactor were studied by transient
      computational fluid dynamic simulation. Molecular-beam quadrupole mass
      spectroscopy (MB-QMS) has been used to analyze the gas phase during ferrocene CVD
      under reaction conditions (1073 K) in the boundary layer near the substrate.
      Field-emission (FE) properties of the nonaligned CNTs were measured for various
      coverages and pore diameters of the alumina. Samples with more dense CNT
      populations provided emitter-number densities up to 48,000 cm(-2) at an electric
      field of 6 V microm(-1). Samples with fewer but well-anchored CNTs in 22-nm pores
      yielded the highest current densities. Up to 83 mA cm(-2) at 7 V microm(-1) in dc
      mode and more than 200 mA cm(-2) at 11 V microm(-1) in pulsed diode operation
      have been achieved from a cathode size of 24 mm2.

PMID- 17514769
TI  - Allogeneic retrovirally transduced, IL-2- and IFN-gamma-secreting cancer cell
      vaccine in patients with hormone refractory prostate cancer--a phase I clinical
      trial.
AB  - BACKGROUND: The purpose of this vaccine study was to determine the safety and
      feasibility of vaccination with an allogeneic prostate carcinoma cell line,
      LNCaP, expressing recombinant interleukin-2 (IL-2) and interferon-gamma (IFN
      gamma) and to evaluate the efficacy of inducing tumor-specific immune responses
      in HLA-A2-matched patients with hormone refractory prostate cancer (HRPC).
      METHODS: In a dose-escalating phase I study, HLA-A2-matched HRPC patients
      received four vaccinations of irradiated allogeneic LNCaP cells retrovirally
      transduced to secrete IL-2 and IFN-gamma at study day 1, 15, 29 and 92 and
      subsequently every 91 days unless tumor progression was evident. RESULTS: Three
      patients receiving the first dose level (7.5 million cells) showed no evidence of
      dose-limiting toxicity or vaccine-related adverse events including autoimmunity.
      One of three patients receiving the second dose level (15 million cells)
      developed a transient self-limiting grade 3 local injection site reaction
      (ulceration) after the eighth vaccination. Vaccine-induced immune responses
      against a broad array of prostate tumor associated antigens were detected in all
      six patients. Two of the three patients receiving the higher dose showed a
      decline in serum prostate-specific antigen (PSA) values of more than 50%, with
      one patient remaining on protocol for 3 years. CONCLUSIONS: Immunisation with the
      allogeneic LNCaP/IL-2/IFN-gamma vaccine is safe and feasible without any dose
      limiting toxicity or autoimmunity. A 50% PSA decline was achieved in two of the
      six patients. This encouraging data provides the scientific rationale for further
      investigation of the vaccine in a phase II trial.

PMID- 17514770
TI  - Inflammation-inducible anti-TNF gene expression mediated by intra-articular
      injection of serotype 5 adeno-associated virus reduces arthritis.
AB  - BACKGROUND: The tumor necrosis factor (TNF)-alpha plays a central role in
      rheumatoid arthritis (RA) and current biotherapies targeting TNF-alpha have a
      major impact on RA treatment. The long-term safety concerns associated with the
      repetitive TNF blockade prompt optimization of therapeutic anti-TNF approaches.
      Since we recently demonstrated that intra-articular gene transfer using a
      recombinant adeno-associated virus serotype 5 (rAAV5) efficiently transduces
      arthritic joints, we evaluate its effect on collagen-induced arthritis (CIA) when
      encoding TNF antagonists. METHODS: Recombinant AAV5 vectors encoding the human
      TNFRp55 extracellular domain fused to the Fc region of mice IgG1 (TR1) or a small
      molecular weight dimeric human TNFRp75 extracellular domain (TR2), under two
      different promoters, the CMV or a chimeric NF-kappaB-based promoter inducible by
      inflammation, were injected into mouse CIA joints. RESULTS: Best protection
      against arthritis was obtained with the rAAV5 encoding the TR1, as reflected by
      delayed disease onset, decreased incidence and severity of joint damage. This
      effect was associated with a transient expression of the anti-TNF agent when
      expressed under a NF-kappaB-responsive promoter, only detectable during disease
      flare, while the antagonist expression was rapidly increased and stable when
      expressed from a CMV promoter. Importantly, using the intra-articular
      administration of the rAAV5-NF-kappaB-TR1 vector, we observed a striking
      correlation between local TR1 expression and inflammation. CONCLUSIONS: These
      findings strongly support the feasibility of improving the safety of anti-TNF
      approaches for the treatment of arthritis by local rAAV5-mediated gene expression
      under an inflammation-responsive promoter, able to provide a limited, transient
      and therapeutically relevant expression of anti-TNF compounds.

PMID- 17514771
TI  - Rituximab monotherapy is highly effective in splenic marginal zone lymphoma.
AB  - Splenectomy has traditionally been considered as a standard first line treatment
      for splenic marginal zone lymphoma (SMZL) conferring a survival advantage over
      chemotherapy. However it carries significant complications, especially in elderly
      patients. The purpose of this retrospective study was to report our experience on
      the efficacy of Rituximab as first line treatment in 16 consecutive SMZL
      patients, diagnosed in our department. The diagnosis was established using
      standard criteria. Patients' median age was 57 years (range, 48-78). Prior to
      treatment initiation all patients had splenomegaly, nine had anemia, five
      lymphocytosis, five neutropenia and six thrombocytopenia. Rituximab was
      administered at a dose of 375 mg/m2/week for 6 consecutive weeks. The overall
      response rate was 100%. After treatment, all patients had a complete resolution
      of splenomegaly along with restoration of their blood counts. Eleven patients
      (69%) achieved a CR, three (19%) unconfirmed CR and two (12%) a PR. Among the
      complete responders seven patients had also a molecular remission. The median
      time to clinical response was 3 weeks (range, 2-6). Rituximab maintenance was
      given to 12 patients. Eleven of them had no evidence of disease progression after
      a median follow-up time of 28.5 months (range, 14-36), while two out of four
      patients who did not receive maintenance, relapsed 7 and 24 months after the
      completion of induction treatment. Median follow-up time for the entire series
      was 29.5 months (range, 15-81). No deaths were recorded during the follow-up
      period. Therapy was well tolerated. The present study demonstrates that rituximab
      is an effective treatment for SMZL and could be considered as a substitute or
      alternative to splenectomy.

PMID- 17514772
TI  - Phase II study of CLAD (cyclophosphamide, liposomal doxorubicin and
      dexamethasone) in patients with advanced multiple myeloma and historical
      comparison to CAD (cyclophosphamide, doxorubicin and dexamethasone).
AB  - The purpose of this study was to assess the efficacy and safety of pegylated
      liposomal doxorubicin in combination with cyclophosphamide and dexamethasone
      (CLAD). In this prospective open-label phase II study, 60 patients with advanced
      multiple myeloma (MM) received three weekly cycles of CLAD, consisting of
      cyclophosphamide 200 mg/m2 i.v. d1-4, pegylated liposomal doxorubicin 20 mg/m2
      i.v. d1 and dexamethasone 40 mg p.o. d1-4 for a maximum of six cycles in absence
      of disease progression. Efficacy and toxicity was compared to our immediate
      historical cohort of 46 patients treated with cyclophosphamide, dexamethasone and
      conventional doxorubicin (CAD). A total of 239 cycles of CLAD and 209 cycles of
      CAD, respectively, were given. The objective response rate was 71% (CLAD) and 74%
      (CAD). Non-cumulative hematological toxicity was predominant in both regimens. It
      was found that CLAD is an active and well-tolerated treatment regimen for MM.
      Response rate is comparable to other anthracycline containing regimens like CAD
      with an advantage in hematological toxicity and lower infectious complications,
      and a presumed advantage of lower cardiotoxicity.

PMID- 17514773
TI  - Synthesis and characterization of tantalum(V) boronate clusters: multifunctional
      Lewis acid cages for binding guests.

PMID- 17514774
TI  - Sodium-mediated manganation: direct mono- and dimanganation of benzene and
      synthesis of a transition-metal inverse-crown complex.

PMID- 17514775
TI  - Adamantaplatensimycin: a bioactive analogue of platensimycin.

PMID- 17514776
TI  - Air pollution and cardiovascular events.

PMID- 17514777
TI  - Inhaled insulin for diabetes mellitus.

PMID- 17514778
TI  - Inhaled insulin for diabetes mellitus.

PMID- 17514779
TI  - Inhaled insulin for diabetes mellitus.

PMID- 17514780
TI  - Assessment in medical education.

PMID- 17514781
TI  - Assessment in medical education.

PMID- 17514782
TI  - Assessment in medical education.

PMID- 17514783
TI  - An optimal method of DNA silver staining in   polyacrylamide gels.
AB  - A silver staining technique has widely been used to detect DNA fragments with
      high sensitivity on polyacrylamide gels. The conventional procedure of the silver
      staining is tedious, which takes about 40-60 min and needs five or six kinds of
      chemicals and four kinds of solutions. Although our previous improved method
      reduced several steps, it still needed six kinds of chemicals. The objective of
      this study was to improve further the existing procedures and develop an optimal
      method for DNA silver staining on polyacrylamide gels. The novel procedure could
      be completed with only four chemicals and two solutions within 20 min. The steps
      of ethanol, acetic acid, and nitric acid precession before silver impregnation
      have been eliminated and the minimal AgNO3 dose has been used in this up-to-date
      method. The polyacrylamide gel of the DNA silver staining displayed a golden
      yellow and transparent background with high sensitivity. The minimum 0.44 and 3.5
      ng of DNA amount could be detected in denaturing and nondenaturing polyacrylamide
      gel, respectively. This result indicated that our optimal method can save time
      and cost, and still keep a high sensitivity for DNA staining in polyacrylamide
      gels.

PMID- 17514784
TI  - Multilocus mutation scanning for the analysis of genetic variation within
      Malassezia (Basidiomycota: Malasseziales).
AB  - Members of the genus Malassezia are budding yeasts, characterized by a thick cell
      wall. Recently, these yeasts have received attention as emerging pathogens. They
      are common commensals on the skin of animals and can become pathogenic under the
      influence of various predisposing factors. Central to studying their taxonomy,
      systematics, and ecology and to diagnosis is the accurate identification of
      species or operational taxonomic units. To overcome the limitations of current
      phenotypic and biochemical methods of identification, a PCR-coupled SSCP
      approach, utilizing sequence variation (0.4-33.5%) in short regions
      (approximately 250-270 bp) of the first internal transcribed spacer (ITS-1) of
      nuclear ribosomal DNA and the chitin synthase-2 gene (chs-2), was assessed for
      the identification and differentiation of different species/genotypes of
      Malassezia, characterized previously by DNA sequencing. Genomic DNA samples (n =
      30) from Malassezia isolates cultured from canine skin scrapings were assessed by
      SSCP analysis of the two different genetic loci, and unequivocal delineation
      between genotypes and species was achieved. This SSCP approach is considered to
      provide a practical tool for the rapid and reliable genetic characterization of
      Malassezia genotypes/species from dogs and for investigating their population
      genetics and ecology. It will also provide a powerful tool for studies of
      Malassezia isolates from other animal species.

PMID- 17514785
TI  - [Notched-noise-BERA: methods and diagnostic use].
AB  - BACKGROUND: As Picton demonstrated with case reports in 1978, thresholds of click
      evoked potentials do not match to pure tone thresholds if hearing loss differs
      across the test frequencies. Thus, he developed a stimulation with brief tone
      pips masked by a notched noise that over the years became the standard method for
      frequency specific threshold estimation. Currently, new technologies like
      auditory steady-state responses and Chirp-evoked potentials promise to overcome
      some disadvantages of the NN-BERA. METHODS: Thus, a systematic review about the
      NN-BERA was needed to further compare the competitive technologies. Literature
      research was performed according to the present guidelines for evidence based
      medicine. It was found that a meta-analysis with data pooling was impossible
      because of massive discrepancies of methods and subjects across the retrieved
      publications. RESULTS: The differences of means between pure tone thresholds and
      NN-BERA-thresholds were up to 12 dB. Standard deviations were 2 to 16 dB and
      generally higher at 0.5 und 1 kHz compared to 2 and 4 kHz. Correlations were r =
      0.84 to r = 0.97. CONCLUSIONS: The NN-BERA faces a growing competition by
      auditory steady state potentials, chirp-evoked potentials, and distortion product
      otoacoustic emissions but serves still as the standard for an objective threshold
      estimation since it's accuracy is well evaluated and the interpretation is
      independent from statistical tests which accuracy is not sufficiently evaluated
      at present.

PMID- 17514786
TI  - Conscious sedation versus monitored anaesthesia care.

PMID- 17514787
TI  - Searching high and low for interactions.

PMID- 17514788
TI  - Multiplexing to the max.
AB  - Researchers demonstrate how microfluidics can be used to both synthesize millions
      of differentially encoded particles for multiplexed in vitro biological detection
      assays, as well as to decode their identities.

PMID- 17514789
TI  - Kinase clamping.
AB  - By introducing two point mutations in the ATP-binding pockets of kinases,
      researchers can specifically and irreversibly inhibit these enzymes and determine
      how much kinase activity is needed for downstream signaling.

PMID- 17514790
TI  - Designer receptors for every body.
AB  - Using a directed evolution approach, researchers demonstrate a way of creating
      'designer' receptors that are specifically activated by a ligand with no other
      biological activity in the cell.

PMID- 17514791
TI  - Optical excitation yin and yang.
AB  - A halorhodopsin can function as the yin to channelrhodopsin-2's yang for
      photoinducible control of neuronal activity.

PMID- 17514792
TI  - Too much of a good thing.
AB  - Culture of primary lymphocytes at physiological oxygen levels better maintains
      intracellular redox state.

PMID- 17514793
TI  - Unprotected synthesis.
AB  - Chemists at The Scripps Research Institute demonstrate that it is possible to
      synthesize complex natural products without the use of protecting groups.

PMID- 17514794
TI  - Protein-protein interactions: better by the dozen.
AB  - A combined reanalysis of the two largest yeast protein-protein interaction
      studies to date provides a large consolidated data set, with a level of accuracy
      matching the reliability of small-scale experiments.

PMID- 17514795
TI  - Challenges ahead for cervical cancer screening.

PMID- 17514796
TI  - Drug costs: how much is too much?

PMID- 17514797
TI  - Testosterone and male fertility in red deer.

PMID- 17514799
TI  - Coordination, not harmonisation.

PMID- 17514798
TI  - Pilot study of human-papilloma-virus vaccine in Uganda.

PMID- 17514800
TI  - Low breast reconstruction rate owed to few referrals?

PMID- 17514802
TI  - Allograft versus autograft for myeloma.

PMID- 17514801
TI  - Zoledronic acid prevents bone loss.

PMID- 17514803
TI  - Adjuvant radiotherapy improves survival in MCC of skin.

PMID- 17514804
TI  - Adenoviral treatment enhances tumour radiosensitivity.

PMID- 17514805
TI  - Using MRI to detect contralateral breast cancer.

PMID- 17514806
TI  - Long-term Mitomycin C is better for bladder cancer.

PMID- 17514807
TI  - Usefulness of CT in patients with early-stage CLL.

PMID- 17514808
TI  - Age-specific PSA screening better.

PMID- 17514809
TI  - Simultaneous surgery can reduce hospital stays.

PMID- 17514810
TI  - Circulating VEGF predicts efficacy of cetuximab.

PMID- 17514811
TI  - Trans-vaginal sonography could improve screening.

PMID- 17514812
TI  - New markers to detect prostate cancer.

PMID- 17514813
TI  - European Parliament increases number of chemicals earmarked for priority action
      by European Commission.

PMID- 17514815
TI  - How times have changed.

PMID- 17514814
TI  - Working with aids orphans.

PMID- 17514816
TI  - Play tells nursing stories thoughtfully.

PMID- 17514817
TI  - Bringing healthy back. Genesis, Symbion bidding heats up equity market.

PMID- 17514818
TI  - Why regular check-ups are still a good idea. An annual "well woman" visit has
      important health benefits--especially the doctor-patient relationship it fosters.

PMID- 17514819
TI  - Pelvic organ prolapse can run in the family.

PMID- 17514820
TI  - Exercise after age 70. There are no official fitness guidelines for older women,
      but the basics are the same at every age.

PMID- 17514821
TI  - Caution in treating temporomandibular disorders. You may be ready to try anything
      for relief. But unproven fixes can cause greater injury and disability.

PMID- 17514822
TI  - By the way, doctor. I have white skin patches on both hands. My doctor says it's
      vitiligo. What causes this, and how can I treat it?

PMID- 17514823
TI  - Moderate exercise: no pain, big gains.

PMID- 17514824
TI  - Lowering cholesterol: is there a limit?

PMID- 17514825
TI  - Autoantibody signatures: a promising new test for prostate cancer.

PMID- 17514826
TI  - On call. Your January issue convinced me that obesity increases the risk of
      prostate cancer. It depresses me a bit, since I'm overweight, so my question is
      both personal and practical: if I lose weight, will I undo the harm?

PMID- 17514827
TI  - [Development of liquid phase immunoassay system using magnetic nanoparticles].
AB  - Biological immunoassay is a major detection system of biological materials from
      patient samples. Our group has been developing a highly sensitive immunoassay
      system using magnetic nanoparticles made from Fe3O4. Since unbound magnetic
      markers randomly move in solvent due to Brownian motion, there is no magnetic
      signal from unbound magnetic markers; therefore, the separation of bound from
      unbound markers (B/F separation) is not required. This advantage means that the
      detection time is greatly decreased in comparison with a normal method using
      fluorescent/enzyme reagent. In this paper, we describe the configuration of the
      developed system and demonstrate the performance of the detection of magnetic
      nanoparticles.

PMID- 17514828
TI  - Clinical management. Formula for inspiration.

PMID- 17514829
TI  - Claim back hospital travel expenses.

PMID- 17514830
TI  - RNAs everywhere: genome-wide annotation of structured RNAs.

PMID- 17514832
TI  - Abstracts of the 20th Annual Symposium on Advanced Wound Care and the Wound
      Healing Society Meeting, April 28-May 1, 2007, Tampa, Florida, USA.

PMID- 17514831
TI  - Increasing confidence of protein-protein interactomes.
AB  - High-throughput experimental methods, such as yeast-two-hybrid and phage display,
      have fairly high levels of false positives (and false negatives). Thus the list
      of protein-protein interactions detected by such experiments would need
      additional wet laboratory validation. It would be useful if the list could be
      prioritized in some way. Advances in computational techniques for assessing the
      reliability of protein-protein interactions detected by such high-throughput
      methods are reviewed in this paper, with a focus on techniques that rely only on
      topological information of the protein interaction network derived from such high
      throughput experiments. In particular, we discuss indices that are abstract
      mathematical characterizations of networks of reliable protein-protein
      interactions--e.g., "interaction generality" (IG), "interaction reliability by
      alternative pathways" (IRAP), and "functional similarity weighting" (FSWeight).
      We also present indices that are based on explicit motifs associated with true
      positive protein interactions--e.g., "new interaction generality" (IG2) and "meso
      scale motifs" (NeMoFinder).

PMID- 17514833
TI  - There's no place like home.

PMID- 17514834
TI  - The use of technology for improved pressure ulcer prevention.

PMID- 17514835
TI  - Taking wound care on the road: the WWCA. Interview by Barbara Zeiger.

PMID- 17514836
TI  - Has anyone seen my data?

PMID- 17514837
TI  - Controlling health care costs: some practical advice. Being proactive can make a
      difference in health and health care costs.

PMID- 17514838
TI  - Believes diet drug use ignores cause of pet obesity.

PMID- 17514839
TI  - The evolution of Gondar's public health college and training center: Che-Che-La
      from an Italian consular office to a medical college.

PMID- 17514840
TI  - Notice of retraction.

PMID- 17514841
TI  - Homosexuality and the Israel defense forces: did lifting the gay ban undermine
      military performance?

PMID- 17514842
TI  - Exploring theories of patriarchy: a perspective from contemporary Bangladesh.

PMID- 17514843
TI  - JCAHO and hospital oversight--the experience of hospitals in Maine.

PMID- 17514844
TI  - Chaos and complexity: applications for healthcare quality and patient safety.
AB  - The new sciences of chaos and complexity are generating considerable interest
      within the social sciences, particularly with regard to organizational
      development, management, and Leadership. This article explores potential
      applications of the concepts of chaos and complexity within the domains of
      healthcare quality and patient safety.

PMID- 17514845
TI  - Learning from unexpected events: a root cause analysis training program.
AB  - Staff members need appropriate training before the investigation and causal
      analysis of accidents in any complex system. Otherwise results will be incomplete
      and will be focused on the Least manageable contributors, such as the unsafe acts
      of frontline operators, regardless of the degree of organizational commitment.
      This is particularly true in healthcare, a field in which errors have
      traditionally been understood in terms of breaches of personal and professional
      accountability. This article outlines an incident investigation and root cause
      analysis workshop developed to address this training need for healthcare
      professionals representing the full spectrum of healthcare settings in Utah and
      Nevada and reviews feedback from participants.

PMID- 17514846
TI  - Challenges to performance-based assessment for community physicians.
AB  - The Joint Commission on Accreditation of Healthcare Organizations requires
      accredited organizations to assess individual competency of physicians granted
      membership on the medical staff. Verification of the competency of physicians
      caring for children in the acute-care setting presents a particular challenge for
      the clinical privileging of community physicians. At Cincinnati Children's
      Hospital, a knowledge-based reappointment method was developed and implemented.
      Using a case-based self-test, the initial phase measured physicians' knowledge of
      evidence-based guidelines for three common pediatric inpatient diagnoses. Future
      methods for tracking individual performance of community-based generalists at the
      time of reappointment were explored through a physician survey. Response was
      positive. This process may help keep community physicians engaged as vital
      members of the hospital staff.

PMID- 17514847
TI  - A computerized surveillance system for the quality of care in childhood asthma.
AB  - This article describes the development of a novel model for quality assurance of
      pediatric asthma using administrative data and clinical guidelines. Children for
      whom drugs for asthma were dispensed during 1998 were recruited from the drug
      dispensing registry of the largest health maintenance organization in the
      southern region of Israel. The Israeli clinical guidelines were translated into a
      list of six markers for inadequate treatment. This list was used for a
      computerized search in the drug registry, and cases with markers were noted as
      cases in which inappropriate treatment was provided. The model was validated by
      proving that there was an association between inappropriate treatment (markers)
      and bad outcomes (emergency room visits, hospitalizations, and healthcare
      utilization). This model creates an interface between administrative and clinical
      information and provides an easy-to-use tool for quality assurance.

PMID- 17514848
TI  - Overcoming challenges to integrating behavioral health into primary care.
AB  - Integrating behavioral healthcare into the primary care setting is associated
      with many benefits; however, plans to integrate care must address several
      challenges. This article identifies the challenges of integrating behavioral
      health specialists into primary care and describes strategies used to overcome
      these challenges.

PMID- 17514849
TI  - Conference brief report: National Patient Safety Foundation's 7th Annual Patient
      Safety Congress "Let's Get On With it-Round 2".

PMID- 17514850
TI  - Five years later--what have we accomplished?

PMID- 17514851
TI  - The launch of Q solutions.

PMID- 17514852
TI  - Organizational change and quality improvement in nursing homes: approaching
      success.
AB  - Nursing home residents' quality of life (QoL) is directly related to the quality
      improvement (QI) processes mandated by federal law. This article describes a 3
      year longitudinal study of QI process innovations in two nursing homes and
      highlights details of a successful 6-month initiative. The initial QI initiatives
      were based on the principles of staff empowerment, enhanced ability through
      training, and financial incentives. After 18 months without measurable success,
      the QI process was modified to include real-time feedback. Two not-for-profit
      nursing homes participated in this study to explore the effect of organizational
      change in nursing homes on residents' quality of care and QoL and staff members'
      job satisfaction. At 6-month intervals, residents and staff participated in
      structured assessments of residents' QoL and quality of care and staff members'
      job satisfaction. When the QI process was modified to include real-time feedback,
      there was a significant reduction in the rate of new pressure ulcers, stage 2 or
      greater (p < .05), in one of the facilities that had struggled with this problem
      for more than 18 months. By examining QI processes in nursing homes, the
      researchers were able to identify some of the obstacles to improving quality of
      care and QoL. Only when the element of real-time feedback was introduced, in
      combination with enhanced staff abilities and financial incentives, were
      substantial improvements seen in key clinical outcomes.

PMID- 17514853
TI  - Beyond interviewing: a 21st-century recruitment process for healthcare quality
      professionals.
AB  - Interview techniques have evolved to include objective testing and situational
      assessment methods, and an applicant for a quality leadership role in today's
      market may encounter these new techniques. For an organization, the use of an
      updated interview process provides greater insight into an applicant's knowledge,
      skills, and abilities. This article offers an overview of these processes,
      insights for organizations and leaders to consider in developing assessment
      strategies, and tips for quality leaders who encounter testing and situational
      assessment methods during a career search. A case study is provided on the use of
      job simulations for recruitment of both a senior director for quality and
      performance improvement and a data management administrator in a regional medical
      center.

PMID- 17514854
TI  - Robert McArtor on MaineHealth and the Maine Quality Forum Initiative. Interview
      by Susan B. Boisvert.

PMID- 17514855
TI  - The quality of preventive medical care for homeless veterans with mental illness.
AB  - The 2003 National Healthcare Disparities Report underscored the need for
      performance measurement of evidence-based preventive services for at-risk
      populations. This study compares receipt of primary care prevention services
      among homeless and nonhomeless veteran patients who received Veterans Affairs
      (VA) medical care services. The study used chart review data on a national sample
      of 94,932 veterans with chronic medical conditions whose care was reviewed
      through the VA External Peer Review Program during 1998 and 1999. Receipt of
      eight preventive services was examined: two measures of immunization, four of
      cancer screening, and two of tobacco use and counseling. In risk-adjusted models,
      recently homeless veterans received 9% fewer prevention services for which they
      were eligible. Modest differences in receiving prevention services between
      domiciled and recently homeless veterans suggest that targeted efforts are needed
      to facilitate access to needed medical services in this population.

PMID- 17514856
TI  - Hospital-level correlation between clinical and service quality performance for
      heart failure treatment.
AB  - A national cross-sectional study correlates the satisfaction ratings of heart
      failure patients (diagnosis related group 127) and the Centers for Medicare &
      Medicaid Services' process-based quality measures for heart failure treatment for
      32 hospitals during the first and second quarters of 2004. Two of the four
      measures of clinical quality showed statistically significant, moderately strong,
      positive correlations with a global measure of satisfaction and with,
      respectively, 5 and 7 subscales of the 10 subscales of satisfaction under
      examination (Pearson's r ranged between .40 and .67, 2-tailed; p < .05). Findings
      demonstrate that quality need not be a zero-sum issue, with clinical quality and
      service quality competing for resources and attention.

PMID- 17514857
TI  - Designing healthy work environments with intention.

PMID- 17514858
TI  - On "smart" patients as consumers.

PMID- 17514859
TI  - Do educational interventions improve management of patients with community
      acquired pneumonia?
AB  - Community-acquired pneumonia (CAP) is the Leading cause of death from infection.
      In order to evaluate physicians' adherence to hospital guidelines for CAP, an
      observational prospective study during two consecutive winter periods at an Irish
      teaching hospital was performed. A series of educational sessions on management
      of CAP was provided for medical staff at the end of the first year. Comparison of
      results showed significant improvement in the rate of blood culture sampling (p <
      .01), sputum sampling (p < .05), and combined blood culture and sputum sampling
      (p < .01). Length of antibiotic treatment was more appropriate in the second
      study year. Results indicate that antibiotic audit and educational interventions
      improve physicians' adherence to hospital guidelines.

PMID- 17514860
TI  - Using evidence-based performance improvement in the community hospital setting.
AB  - Lack of research expertise and participation in the nonacademic setting hinders
      evidence-based performance improvement in community hospitals. Research
      opportunities are limited in small hospitals, and staff nurses often are
      unfamiliar with research terminology and practice. This article explores one
      community hospitals success in bringing a research focus into its performance
      improvement initiatives.

PMID- 17514861
TI  - Integrating patient safety indicators into patient safety programs.
AB  - Patient safety indicators (PSIs) can be a valuable reporting tool to incorporate
      into patient safety plans to monitor performance and identify areas that warrant
      further investigation. The Agency for Healthcare Research and Quality (AHRQ)
      developed PSIs as a low-cost tool to enable hospitals to monitor safety patterns
      within specific patient populations. Screening performance and evaluating it
      against empirical rates provided by AHRQ are the cornerstones of the PSI system.

PMID- 17514862
TI  - Joan M. Marren on home healthcare quality. Interview by Deborah Flores and
      Margaret V McDonald.

PMID- 17514863
TI  - Assessment of chiropractic outcomes for low back pain and neck pain: a health
      plan quality incentive model.
AB  - Blue Cross and Blue Shield of Minnesota conducted a quality improvement project
      to quantify and improve the clinical and functional outcomes of low back pain and
      neck pain patients in a chiropractic network. Improved outcomes were encouraged
      through a financial incentive for implementation of standard clinical outcome
      measurement tools, quarterly feedback to individual practices, and a face-to-face
      meeting to share best practices. Although a large database on baseline neck pain
      and low back pain and functional disability was generated, and clinically and
      statistically significant improvements in outcomes were documented, progressive
      improvement in outcomes over the 4-year project period was not found.

PMID- 17514865
TI  - Are conflicts and disruptive behavior putting patients at risk at your hospital?

PMID- 17514864
TI  - Evaluating quality of primary care using the electronic medical record.
AB  - Healthcare organizations are under increasing pressure to evaluate and report the
      level of quality in their health services. The electronic medical record (EMR)
      has been used in acute care settings to provide clinical data for quality
      evaluations. The implementation of the EMR in primary care settings is a more
      recent development, and as a result, the EMR has not been widely used to evaluate
      quality in primary care. Little research exists that uses the primary care
      medical record as a source of data. What remains to be seen is the extent to
      which EMRs contain the variables needed to address quality of primary care. This
      article describes a study that investigated the viability of the EMR as a
      database for evaluating quality in a women's primary health clinic.

PMID- 17514866
TI  - Database compares safety culture survey results.

PMID- 17514867
TI  - Tips to make your hospital patient-friendly environment.

PMID- 17514868
TI  - Surveyors: handoff process is "best they've ever seen".

PMID- 17514869
TI  - Exploring effects of different nonsteroidal antiinflammatory drugs on
      malondialdehyde profile.
AB  - As a part of our ongoing effort to explore drug induced lipid peroxidation in
      relation to drug-induced toxicity, this study was undertaken to determine whether
      nonsteroidal anti-inflammatory drugs (NSAIDs), namely, diclofenac sodium,
      ibuprofen, flurbiprofen, paracetamol, nimesulide, celecoxib and indomethacin are
      involved in oxidative/antioxidative processes by determining malondialdehyde
      (MDA) concentration as an index of lipid peroxidation. Considering lipid
      peroxidation, a possible mediator of toxicity, an attempt was made to see the
      suppressive action of ascorbic acid, a conventional antioxidant compound, on
      NSAID-induced lipid peroxidation. It was found that diclofenac sodium, ibuprofen,
      flurbiprofen and paracetamol exerted statistically significant decrease of MDA
      content, suggesting a potential of the molecules to suppress the lipid
      peroxidation. At earlier stage of incubation nimesulide shows statistically
      significant decrease of MDA content followed by lipid peroxidation induction at
      the later stage of incubation period, suggesting involvement of nimesulide in
      antioxidative/oxidative processes. Celecoxib and indomethacin both exerted
      statistically significant increase of MDA content, representing significant
      peroxidation activity. Ascorbic acid, a promising antioxidant, could
      significantly reduce celecoxib and indomethacin induced lipid peroxidation.

PMID- 17514870
TI  - The alkoxyacetic acids as calcium and magnesium chelating agents in vitro.
AB  - Alkoxyacetic acids (AAAs) are known urinary metabolites of the corresponding
      ethylene glycol monoalkyl ethers with a wide range of industrial and domestic
      applications. Hemolysis is the principal toxic effect of AAAs in humans and
      animals. The mechanism of red-cell damage is not known. It is suggested that some
      disturbances in ion balance, mainly related to calcium are one of the reasons of
      hemolysis. No comparative studies in the available literature on the chelating
      properties of numerous AAAs in respect to calcium were found. Therefore, a
      comparison was made between chelating effects of five AAAs on calcium and
      magnesium in vitro. It was demonstrated that calcium was bound at lower AAAs
      concentrations than magnesium. The chelating effect of AAAs expressed by EC50
      values was positively correlated with both pKa values and Log P values of the
      examined acids. The obtained data indicate that the acidity and hydrophilic
      properties are responsible for the chelating effect of AAAs on calcium and
      magnesium in vitro. These data do not provide an explanation for differences in
      the hemolytic activity of the examined compounds.

PMID- 17514871
TI  - Synthesis, characterization, antibacterial and cytotoxicity studies on some mixed
      ligand Th(IV) complexes.
AB  - Mixed ligand Th(IV) complexes of the type [M(Q)2LNO3.H2O] have been synthesized
      using 8-hydroxyquinoline (HQ) as a primary ligand and N- and/or O- donor amino
      acids (HL) such as L-alanine, L-phenylalanine, L-serine and L-tyrosine as
      secondary ligands. The metal complexes have been characterized on the basis of
      elemental analysis, electrical conductance, room temperature magnetic
      susceptibility measurements, spectral and thermal studies. The electrical
      conductance studies of the complexes in DMF at 10(-3) M concentration indicate
      their non-electrolytic nature. Room temperature magnetic susceptibility
      measurements revealed diamagnetic nature of the complexes. Electronic absorption
      spectra of the complexes show intra-ligand and charge transfer transitions,
      respectively. The thermal analysis data of the complexes indicate the presence of
      a coordinated water molecule. The tube dilution method has been used to study the
      antibacterial activity of the complexes against the pathogenic bacteria S. aureus
      and E. coli. The results have been compared against those of control
      tetracycline, which was screened simultaneously and indicate mild antibacterial
      activity of the complexes. The representative complex has been screened for
      cytotoxicity (IC50) studies against Ehrlich ascites cells and Daltons lymphoma
      ascites cells and shows low cytotoxic activity.

PMID- 17514872
TI  - Synthesis and anticonvulsant properties of new N-phenylamino derivatives of 2
      azaspiro[4.4]nonane, 2-azaspiro[4.5]decane-1,3-dione and 3-cyclohexylpyrrolidine
      2,5-dione. Part IV.
AB  - To continue our systematic SAR studies a series of N-phenylamino derivatives of 2
      azaspiro[4.4]nonane-, 2-azaspiro[4.5]decane-, 6-methyl-2-azaspiro[4.5]decane-1,3
      dione and 3-cyclohexylpyrrolidine-2,5-dione were synthesized and tested for their
      anticonvulsant activity in the maximum electroshock seizure (MES) and
      subcutaneous metrazole seizure threshold (sc. Met) tests. Among those molecules
      the most potent were N-(4-methylphenyl)-amino-2-azaspiro[4.4]nonane-1,3-dione
      [V], N-(2-trifluoromethylphenyl)-amino-2-azaspiro[4.4]nonane-1,3-dione [VI], N-(3
      methylphenyl)-amino-2-azaspiro[4.5]decane-1,3-dione [VIII] and N-(4-methylphenyl)
      amino-6-methyl-2-azaspiro[4.5]decane-1,3-dione [XIV], which inhibited the
      seizures mainly in the sc. Met test. The obtained results revealed that
      anticonvulsant activity depended on the presence and the position of the methyl
      or trifluoromethyl groups at the aryl moiety, as well as the size and the manner
      of attachment of the cycloalkyl system at the position-3 of the pyrrolidine-2,5
      dione ring.

PMID- 17514873
TI  - Cardiac glycosides in cancer research and cancer therapy.
AB  - The well known and accepted mode of action of cardiac glycosides is inhibition of
      the ubiquitous plasma membrane Na+, K+-ATPase that leads to increased
      intracellular Ca2+ ion concentrations. Ca2+ ions play pivotal role in many
      signaling pathways including those regulating apoptosis. It has been suggested
      that some forms of cardiac glycosides inhibit proliferation and induce apoptosis
      in prostate cancer cells in clinically relevant concentrations. It was also found
      out that the degree to which cardiac glycosides inhibited cancer cell growth was
      correlated to topoisomerase II-inhibiting activity. Digitoxin at concentrations
      found in cardiac patients induced levels of DNA-topoisomerase II cleavable
      complexes similar to etoposide, a topoisomerase II poison widely used in cancer
      chemotherapy. Cardiac glycosides can also regulate one of the most potent
      angiogenesis promoting substances, fibroblast growth factor-2 (FGF-2), and may
      inhibit activation of the transcription factor NF-kappaB. FGF-2 and NF-kappaB are
      relevant targets for anticancer drugs. There is growing interest in evaluating
      the oleander products and possibly other cardiac glycosides as antineoplastic
      agents. The first of these therapies to be developed in the United States is a
      patented, water-soluble oleander extract called Anvirzel.

PMID- 17514874
TI  - Aqueous ginger extract ameliorates paraben induced cytotoxicity.
AB  - The present investigation is an attempt to examine the ameliorative effect of
      aqueous ginger extract on cytotoxicity induced by paraben (p-hydroxybenzoic acid)
      on red blood cells (RBC) in vitro. Blood samples collected in EDTA vials from
      healthy adult human beings (25-30 years) were used for preparation of RBC
      suspension in saline. The saline suspension of RBC was treated with paraben with
      and without ginger extracts. The results revealed that addition of paraben to RBC
      suspension caused significant increase in the rate of hemolysis. However,
      concurrent addition of paraben (150 microg/mL) and ginger extract caused
      significant concentration-dependent retardation in paraben-induced hemolysis. The
      decrease in hemolysis was almost dose-

PMID- 17514875
TI  - The presence of microorganisms in some common excipients used in tablet
      formulation.
AB  - Strict measure on the need to control microbial contamination in the formulation
      of solid dosage forms such as tablets and capsules are not usually in place as is
      done in other pharmaceutical preparations. The presence of microorganisms in some
      common excipients such as starch and lactose powders, and distilled water used in
      tablet formulation was investigated in this study. Organisms isolated were
      Geotrichuim and Aspergillus spp as well as two strains of Staphylococcus aureus.
      Lactose tablets were further formulated using 5% starch as binder. Some of the
      isolated organisms were, in turn, inoculated into these tablets and stored over a
      period of several weeks. The physical properties of these tablets were determined
      at various time intervals. Marked increases in the disintegration times of these
      tablets were observed, while there was a decrease in the hardness property for
      both the fungi and bacteria. These observed effects have serious implications in
      the overall bioavailability of drugs such as tablets formulated from contaminated
      excipients.

PMID- 17514876
TI  - The effect of saccharic alcohols on rheological parameters of dental anti
      inflammatory gels and on pharmaceutical availability of sodium ibuprofen.
AB  - A prescription of model dental anti-inflammatory gels has been worked out on the
      base of cellulose derivatives with the content of saccharic alcohols: xylitol and
      sorbitol. The effect of saccharic alcohol on rheological parameters
      (extensibility and viscosity) of the produced gels was tested. Taking into
      account application, the most beneficial results of rheological tests were
      obtained for gels containing in their prescription both xylitol and sorbitol in
      the quantity ratio 1:1. These gels are characterised by high extensibility, low
      viscosity and low value of yield stress. Theoretical diffusion coefficient of
      sodium ibuprofen calculated on the basis of viscosity measurements points to the
      highest pharmaceutical availability of therapeutic agent from model gels with
      xylitol and sorbitol. The above has been confirmed by in vitro studies of the
      sodium ibuprofen kinetics of release from gel to the dialysis fluid.

PMID- 17514877
TI  - Solubility of selected derivatives of 1,4-benzodiazepin-2-one in solid
      dispersions in PEG 6000.
AB  - Pharmaceutical availability of diazepam, oxazepam and nitrazepam from solid
      dispersions of PEG 6000 have been studied in comparison with corresponding
      physical mixtures and pure benzodiazepines. Selected derivatives of 1,4
      benzodiazepin-2-one are poorly water soluble drugs. The aim of this work was to
      report the properties of diazepam- and nitrazepam-PEG 6000 solid dispersions.
      Differential scanning calorimetry (DSC) and X-ray diffraction were used to
      characterize the solid dispersions. The effect of PEG 6000 on the dissolution of
      selected derivatives of 1,4-benzodiazepin-2-one was investigated. The dissolution
      of diazepam, oxazepam and nitrazepam from its solid dispersions increased in the
      presence of PEG 6000.

PMID- 17514878
TI  - Evaluation of zidovudine encapsulated ethylcellulose microspheres prepared by
      water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion technique.
AB  - The preparation of zidovudine-loaded ethylcellulose microspheres by w/o/o double
      emulsion solvent diffusion method with high entrapment capacity and sustained
      release is described. A mixed solvent system (MSS) consisting of acetonitrile and
      dichloromethane in a 1:1 ratio and light liquid paraffin was selected as primary
      and secondary oil phases, respectively. Span 80 was used as the secondary
      surfactant for stabilizing the external oil phase. Spherical free flowing
      microspheres were obtained. The prepared microspheres were characterized by
      entrapment efficiency, in vitro release behavior, differential scanning
      calorimetry (DSC) and scanning electron microscopy (SEM). The drug-loaded
      microspheres showed 32 - 55% entrapment capacity. The in vitro release profile
      could be altered significantly by changing various processing and formulation
      parameters to give sustained release of drug from the microspheres. The DSC
      thermograms confirmed the absence of any drug-polymer interaction. SEM studies
      showed that the microspheres were spherical and porous in nature. The in vitro
      release profiles from microspheres of different polymer-drug ratios were best
      fitted to Higuchi model with high correlation coefficient and the n value
      obtained from Korsmeyer-Peppas model was ranged between 0.23 - 0.54. The drug
      release was found to be diffusion controlled mechanism.

PMID- 17514879
TI  - Effect of epsilon-aminocaproylamino acids on fibrin formation.
AB  - Effect of three epsilon-aminocaproylamino acids with significant antifibrinolytic
      activity on polymerization of fibrin monomer, clot retraction, fibrin structure,
      prothrombin consumption and thrombin activity was examined. epsilon-Aminocaproyl
      L-norleucine and epsilon-aminocaproyl-L-leucine were weak inhibitors of thrombin
      activity and epsilon-aminocaproyl-L-norleucine slightly inhibited polymerization
      of fibrin monomers.

PMID- 17514880
TI  - The urothelium cell culture on the starch scaffold.
AB  - The etiology of the interstitial cystitis (IC) is believed to be a dysfunction of
      the bladder glycosaminoglycan (GAG) protective layer of the urothelial cells.
      Management of interstitial cystitis (IC) is pure empirical. The aim of this study
      was to establish primary rabbit urothelial cells (PRUCC) affinity to complex
      sugar scaffold in vitro. The primary rabbit urothelial cells culture (PRUCC) was
      set up. The cells were cultured in Jouan IG 150 incubator in temperature of 370C
      and humidified atmosphere containing 5% of CO2. The multi-well culture plates
      were covered with potato starch. PRUCC was seeded on the starch scaffold. On the
      7th day the starch was removed. Culture analysis and photo documentation was done
      under inverted microscope. There was no disruption of the monolayer under the
      starch and the cells morphology was comparable to the rabbit urothelial cells in
      culture. No inhibitory effect on the PRUCC was observed. The colonies of the
      urothelial cells were formed over the starch grains. The athor postulate that
      urothelial cells have affinity to the complex sugar compounds. There is strong
      evidence that sugar complex compounds could be used in the treatment of the IC.

PMID- 17514881
TI  - Annual Award for Clinical Research in Periodontology.

PMID- 17514882
TI  - Three-dimensional ridge augmentation with xenograft and recombinant human
      platelet-derived growth factor-BB in humans: report of two cases.
AB  - The present paper reports on two patients who underwent three-dimensional ridge
      augmentation using a xenograft in combination with recombinant human platelet
      derived growth factor-BB (rhPDGF-BB). Patient 1 received a deproteinized bovine
      block infused with PDGF and secured to the alveolar crest by two fixation screws
      to augment the crest horizontally. After 5 months, implants were successfully
      placed. Patient 2 underwent a vertical ridge augmentation procedure that combined
      deproteinized bovine bone particles embedded in a collagen matrix soaked in PDGF
      Three titanium dental implants were placed in each patient 5 months later.
      Clinical and histologic results showed excellent soft and hard tissue healing.
      Bone had regenerated throughout the whole area and the xenograft particles were
      embedded in bone, which presented resorption lacunae close to areas with ongoing
      bone formation. This indicated that, in augmented areas, intense physiologic
      remodeling was ongoing. No data exist concerning three-dimensional bone
      augmentation using PDGF and a xenograft in humans. This report suggests that the
      use of rhPDGF-BB in combination with a deproteinized bovine graft may have the
      potential to regenerate large three-dimensional alveolar defects in humans.

PMID- 17514883
TI  - Achieving natural-looking morphology and surface textures in anterior ceramic
      fixed rehabilitations.
AB  - This article describes a procedure to achieve natural-looking morphology and
      surface textures in anterior ceramic restorations. The natural dentition serves
      as an atlas to interpret and mimic the orientation and location of dental
      anatomic structures. Transition angles and ridges; proximal slopes; labial
      grooves; the cervical, middle, and incisal thirds of the buccal surface; the
      lingual central concavity; and the lingual transition ridges should all be
      mimicked by the prosthetic work to achieve esthetic integration. The position of
      buccal transition ridges directly influences the buccal mesiodistal dimension-the
      so-called "visual width." Once the desired morphology is obtained, a gold powder
      is used to outline its surface texture. This uniform golden appearance allows for
      precise identification of specific surface features such as ridges, grooves, and
      sulci for their consequent mimicking onto the ceramic surface. Specific surface
      texture characteristics reflect light and thus enhance visual dimensions of the
      rehabilitation and its final esthetic integration.

PMID- 17514884
TI  - Piezoelectric osteotomy for intraoral harvesting of bone blocks.
AB  - Grafting with intraoral bone blocks is a good way to reconstruct severe
      horizontal and vertical bone resorption in future implant sites. The Piezosurgery
      System (Mectron) creates an effective osteotomy with minimal or no trauma to soft
      tissue, in contrast to conventional surgical burs or saws. In addition,
      piezoelectric surgery produces less vibration and noise because it uses
      microvibration, in contrast to the macrovibration and extreme noise that occur
      with a surgical saw or bur. Microvibration and reduced noise minimize a patient's
      psychologic stress and fear during osteotomy under local anesthesia. The purpose
      of this article is to describe the harvesting of intraoral bone blocks using the
      piezoelectric surgery device.

PMID- 17514885
TI  - An alternative technique to the harvesting of a connective tissue graft from a
      thin palate: enhanced wound healing.
AB  - This article describes an alternative surgical approach to the harvesting of
      subepithelial connective tissue grafts from thin palates. A partial-thickness
      flap is raised, and a graft composed of epithelium and connective tissue is
      removed from the palate. The superficial layer (epithelium and a thin zone of
      connective tissue) is then dissected from the graft and replaced at the donor
      site to facilitate faster healing. The subjacent layer of connective tissue is
      placed as needed to obtain root coverage. The clinical application of this
      technique is described in two patients with multiple gingival recessions.

PMID- 17514886
TI  - Computer-assisted implant placement: scan template, simplant, surgiguide, and
      SAFE system.
AB  - Computer-driven implant dentistry uses the latest technology to coordinate every
      aspect of implant treatment. It provides a means with which to control the
      placement of implants with a high degree of accuracy. This is important, since
      accuracy has a direct bearing on the safety, esthetics, invasiveness, and cost of
      implant treatment. Computer-driven implant dentistry must be conceived as a chain
      in which every link is related to the others. Within this chain, there are
      elements that can be employed to maximize the benefits realized by computer
      guided implant dentistry. A scan template is a radiologic template that permits
      visualization of the prosthetic plan prior to treatment and determines the course
      of implant treatment from the perspective of esthetics. The SimPlant software
      program (Materialise) allows implants to be planned in two and three dimensions
      using data received from a computerized tomographic scan. The resulting implant
      plan can be transferred to the mouth and implemented by means of a
      stereolithographic surgical guide (SurgiGuide, Materialise). Finally, the SAFE
      System (Materialise) is used for guided implant placement. It is associated with
      dedicated drilling devices and can be used in combination with SurgiGuides or
      with traditional acrylic resin guides manufactured by the dental lab on a
      synthetic plaster cast.

PMID- 17514887
TI  - Regeneration of standardized mandibular bone defects using expanded
      polytetrafluoroethylene membrane and various bone fillers.
AB  - The purpose of this study was to evaluate the new bone formation and
      biodegradability of various bone fillers placed underneath a nonresorbable
      membrane (expanded polytetrafluoroethylene [e-PTFE]) in standardized defects in a
      beagle dog model. Mandibular premolars and first molars were extracted
      bilaterally in six adult female beagle dogs. Three months after the extractions,
      six rectangular defects (4 mm apicocoronally, 7 mm mesiodistally, and the entire
      width of the ridge buccolingually) were surgically created in the alveolar
      processes. All defects were covered with an e-PTFE membrane and stabilized
      buccally with stainless steel fixation screws. Five different bone fillers were
      placed under the membranes in a random configuration in each dog: autogenous
      bone, demineralized freeze-dried bone, anorganic bovine bone, tricalcium
      phosphate granules, and collagen sponge. One site in each animal was treated with
      the e-PTFE membrane alone. Following an 8-month healing period, a bone core was
      harvested from each grafted site using a trephine drill. Samples from each of the
      grafted sites were evaluated histologically and histometrically for their bone
      regenerative potential. The result of this study demonstrated a positive effect
      of bone fillers on bone regeneration when combined with a nonresorbable membrane;
      however, no significant differences were found between the various bone fillers
      in terms of their regenerative potential.

PMID- 17514888
TI  - Prosthetic success with a maxillary immediate-loading protocol in the multiple
      risk patient.
AB  - The application of immediate loading of implants in the edentulous maxilla in
      multiple-risk patients is presented. Five partially edentulous patients attended
      with failing prostheses supported by hopeless teeth. An immediate-loading
      protocol was proposed because the patients rejected provisionalization with a
      removable prosthesis. Multiple teeth were extracted, and 44 immediately loaded
      implants were placed, most of them (55.5% to 88.9%) in fresh extraction sites, to
      support a cross-arch prosthesis that was loaded 3 to 4 days after surgery. The
      overall implant failure rate was 13.4%; in healed sites it was 20% (2/10) and in
      fresh extraction sites it was 8.82% (3/34). Prosthetic success was 100%. The
      overall failure rate was higher than is usually seen with the standard delayed
      loading approach. Nevertheless, this immediate-loading protocol was satisfactory
      for the patients and the practitioner because prosthetic success was maintained
      during the provisionalization phase.

PMID- 17514889
TI  - Clinical evaluation of a combined regenerative technique with enamel matrix
      derivative, bone grafts, and guided tissue regeneration.
AB  - The goal of this study was to evaluate the clinical changes obtained when intra
      bony defects were treated with an enamel matrix derivative (EMD), a bone graft,
      and guided tissue regeneration. Fifty patients with a periodontal defect not
      associated with a furcation and with an attachment loss of at least 7.0 mm were
      included in this study. Full-thickness flaps were reflected, the roots were
      planed, EMD was applied, a demineralized freeze-dried bone allograft combined
      with EMD was placed, a bioabsorbable membrane was placed, and more EMD was
      applied. The defect areas were then sutured. At a mean of 5.3 months after
      treatment, there was a mean increase in recession of 0.7 mm, a mean reduction in
      probing depth of 5.7 mm, and a mean gain in attachment level of 5.0 mm. In this
      study there was more recession in smokers than in nonsmokers and in defects
      associated with anterior teeth. Additionally, the deeper defects (those with
      greater probing depths and attachment level loss) had the greatest reductions in
      probing depth and gains in attachment level. Based on this study, this technique
      proved itself to be an effective method to improve the clinical situation when
      treating periodontal defects not involving furcations.

PMID- 17514890
TI  - Checking the occlusal relationships of complete dentures via a remount procedure.
AB  - Correct occlusal relationships are part of the successful prosthetic treatment of
      edentulous patients. Occlusal checking should be performed via a remount
      procedure because denture base materials and fabrication procedures cannot
      provide dimensionally accurate complete dentures. Occlusal errors caused by the
      adjustment of denture bases to the denture foundation after a certain period of
      wearing can also be corrected by means of remounting. The following remount
      procedures for complete dentures are described: fabrication of transfer casts,
      transfer of a maxillary denture with a facebow, centric relation record, and
      mounting of dentures with transfer casts in an articulator with a dental stone.
      Deflective occlusal contacts of denture teeth in centric occlusion can be
      eliminated by selective grinding and by tooth-guided excursive movements. In
      complete denture treatment, priority is given to anterior/canine-guided
      occlusion.

PMID- 17514891
TI  - [Neural induction: new achievements and perspectives].
AB  - Neural differentiation is specified for the first time during vertebrate's
      development in a part of cells of the embryonic ectoderm under the influence of
      signals emanating from neighboring tissues: the phenomenon of neural induction.
      As it was established more then 10 years ago by experiments with the Xenopus
      embryos, the inhibition of BMP signaling cascade in precocious of neural cells
      plays the main role in this phenomenon. As a result, the epidermal
      differentiation program is blocked in these cells, and instead the neural program
      appears to be activated in them on default. This so-called the default model of
      neural induction was also confirmed by experiments in other organisms. At the
      same time, an important role of FGF and Wnt signaling cascades in modulation of
      BMP cascade during neural induction was recently established. Identification and
      investigation of many novel proteins involved in the process of neural induction
      allows one to come back at the novel level, namely at the level of mathematical
      modeling, to one of the basic challenge of developmental biology: the problem of
      spatial patterning of cell differentiation during embryogenesis.

PMID- 17514892
TI  - [Directed import of macromolecules into mitochondria].
AB  - Mitochondria are multifunctional organelles of eukaryotic cells that provide the
      energy for the cells by oxidative phosphorylation, play an important role in the
      apoptosis and take part in Fe-S clusters formation, fatty acids oxidation and
      synthesis of some aminoacids. They contain their own genome and are able to
      transcribe and to translate it. However, the vast majority of the macromolecules
      which function inside the mitochondria are imported into these organelles from
      the cytoplasm. The imported macromolecules include proteins and several types of
      small RNAs. Protein import is a universal process and its mechanism is conserved
      among all species. This mechanism is now known in detail. RNA import was shown to
      occur in several groups of eukaryotes, while the pool of imported RNA molecules
      varies in different organisms. Although the knowledge about the mechanisms of RNA
      import is less extensive than for the proteins, it becomes clear that these
      mechanisms are not universal among all the species possessing this pathway. In
      this review, we summarize the data about the import of macromolecules mentioned
      above into mitochondria.

PMID- 17514893
TI  - [Mobile elements and evolution].
AB  - Mobile elements (ME) represent an important component of the genome of all
      organisms studied so far. ME belong to two major classes differing by the
      mechanism of transposition. Class I ME transpose using RNA intermediate and
      reverse transcriptase, while class II elements encode their own transposase and
      may transpose by cut and paste mechanism. Intra and intergenomic distribution of
      various classes of ME is discussed in the review. An important role of various
      groups of ME in regulation of cellular genes is also documented. The data
      accumulated enable to suggest that multiple invasions of ME with subsequent
      amplification in the host genome may significantly contribute to the adaptation
      of population to drastic changes in environment. Various roles of ME in the
      evolution of higher organisms including speciation process are discussed.

PMID- 17514894
TI  - [Small nucleolar RNAs].
AB  - Small nucleolar RNAs (snoRNAs) are an abundant class of non-protein-coding RNAs.
      In association with proteins they perform two most frequent nucleotide
      modifications in rRNAs and some other cellular RNAs: 2'-O-ribose methylation and
      pseudouridylation. SnoRNAs also participate in pre-rRNA cleavage and telomerase
      functions. Most snoRNAs fall into two families, box C/D and H/ACA, distinguished
      by the presence of conserved sequence boxes. Although C/D and H/ACA snoRNP
      proteins contain homologous regions, the assembly of these RNPs significantly
      differ. In addition, snoRNAs include the RNA component of RNAses P and MRP. The
      structure and function of small RNPs from Cajal bodies (small organelles
      associated with nucleoli) similar to snoRNP are also discussed.

PMID- 17514895
TI  - [RNA editing].
AB  - RNA editing is a collective term referring to a plethora of reactions that
      ultimately lead to changes in RNA nucleotide sequence apart from splicing, 5'
      capping or 3' end processing. Spread throughout the Eukarya, RNA editing creates
      genetic information de novo, alters decoding capacity, or influences structure
      and stability of RNA by inserting, deleting or modifying nucleotides.
      Evolutionarily unrelated, co-transcriptional or post-transcriptional mechanisms
      include RNA polymerase stuttering, guide RNA-directed cascades of nucleolytic and
      phosphoryl transfer reactions, site-specific deamination and others. Here, I
      discuss recent advances in the enzymology of various RNA editing systems,
      focusing on the diversity of mechanisms that change the RNA sequence in order to
      fulfill a specific biological function, even if the latter is not always
      apparent.

PMID- 17514896
TI  - [Messenger RNA movement on the ribosome].
AB  - Recent X-ray and cryo-EM studies of 70S ribosome complexes containing different
      types of messenger RNAs (mRNA) and transfer RNA (tRNA) have been reviewed.
      Changes of the mRNA path on the ribosome at initiation and elongation states have
      been described. Authors suggested, that the specific region of ribosomal 30S
      subunit ("platform") is a ribosome binding site of regulatory domains of mRNA
      which locates on the non-translated 5'-end of the mRNA.

PMID- 17514897
TI  - [Scientific and practical applications of molecular colonies].
AB  - Reviewed are the history of invention of the molecular colony technique, also
      known under name "polony technology", applications of this method to studies of
      reactions between single RNA molecules, ultrasensitive diagnostics, gene cloning
      and screening in vitro, and also concepts on the origin of life that consider
      molecular colonies as a prototype of living organisms.

PMID- 17514898
TI  - [Structured proteins and proteins with internal disorder].
AB  - The point of view that a uniquely folded protein tertiary structure is required
      for the protein functioning has been prevailing in the literature quite recently.
      However of lately it has been found that many proteins in a cell have no such
      structure in an isolated state, though they have a well-defined function in
      physiological conditions. These proteins were named as proteins with natural or
      internal disorder. The portion of disordered regions in such proteins may vary
      from a sequence of several amino acids to a completely disordered sequence
      containing from tens to hundreds of amino acids. The main difference of these
      proteins from the structured (globular) ones is that they have no unique tertiary
      structure in an isolated state and acquire it after interaction with their
      partners. Their conformation in such a complex depends on the interacting partner
      and not only on their own amino acid sequence, which is specific for structured
      (globular) proteins. The problem of structural and functional relations in the
      structured proteins and proteins with internal disorder is discussed in this
      review. The complexity of the problem and its potential solutions are illustrated
      by the example of elongation factors EFlA.

PMID- 17514899
TI  - [Protein splicing].
AB  - Protein splicing is a post-translational autocatalytic excision of internal
      protein sequence (intein) with the subsequent ligation of the flanking
      polypeptides (exteins). This process doesn't require any cofactors or enzymes,
      which distinguish it from other variants of protein processing. Protein splicing
      is catalyzed by Hint-domain - internal intein's domain. In review the main
      molecular mechanisms of this process are described. Function of analogous Hint
      domains of other proteins families (Hh-proteins, BIL-domains etc) are considered.
      The analysis of inteins characteristic to different branches of life illustrates
      the role of horizontal transfer in intein's distribution and evolution. A
      possible role of inteins in regulation of different cell processes is discussed.

PMID- 17514900
TI  - [Molecular basics of Alzheimer's disease].
AB  - Studies of molecular mechanisms for Alzheimer's Disease have led to the two major
      achievements. First, genes with mutations causing Alzheimer's Disease (presenilin
      genes PSI, PS2 and APP) or bearing a risk factor polymorphism (ApoE) for
      Alzheimer's Disease were described. Second, the new type of proteases and
      mechanisms of regulation of cellular differentiation and development by processes
      of intramembrane proteolysis were identified. These mechanisms, apparently, are
      universal for various cell types and organisms. Presenilin is a catalytic
      component of tetra-protein complex (epsilon-/gamma-secretase) cleaving type I
      transmembrane proteins. Other recently discovered aspartate proteases, IMPAS/SPP,
      cleave type II transmembrane proteins. Processing of transmembrane proteins by
      cellular intramembrane proteases results in production of signal peptides,
      transcriptional factors and short hydrophobic proteins (fragments of
      transmembrane domains), which may have a physiological function or play a key
      role in patogenic events associated with ageing (e.g., beta-amyloid formation in
      Alzheimer's Disease). To date approximately 160 mutations in PSI gene, more than
      10 mutations in PS2 gene and 21 mutations in APP gene were described. Early
      preclinical diagnostics of some early forms of Alzheimer's Disease became
      possible. Since patogeneses of early and late onset forms of Alzheimer's Disease
      are similar, identification of molecular or epigenetic factors affecting primary
      molecular mechanisms (intramembrane or membrane associated proteolysis)
      underlying the disease may ultimately contribute to development of rational
      therapy for Alzheimer's Disease.

PMID- 17514901
TI  - [Neurodegenerative amyloidoses: the yeast model].
AB  - More than 20 human diseases are related to protein misfolding which causes
      formation of amyloids, fibrillar aggregates of normally soluble proteins. Such
      diseases are called amyloid diseases or amyloidoses. Of them only prion diseases
      are transmissible. Amyloids of the prion type are described in lower eukaryotes.
      However, in contrast to mammalian prions, which cause incurable neurodegenerative
      diseases, prions of lower eukaryotes are related to some non-chromosomally
      inherited phenotypic traits. Here we summarize the results of studies of prions
      of the yeast Saccharomyces cerevisiae and of the use of yeast model for
      investigation of some human amyloidoses, such as prion diseases, Alzheimer's,
      Parkinson's, and Huntington's diseases.

PMID- 17514902
TI  - [Oncoimmunology: some fundamental problems of cancer immunotherapy].
AB  - In this review we briefly discuss several central problems of modem
      oncoimmunology. We review the controversies surrounding the concept of
      immunological surveillance, as well as the problem of immunological tolerance to
      tumors. The discovery of tumor antigens has a great advance towards
      identification of possible therapeutic targets. However, antigen-specific
      vaccinations against cancer so far have a very limited use, mainly for prevention
      of virus-associated cancers, which is essentially based on anti-viral immune
      response. On the other hand, antibodies to cancer antigens are being widely used
      in cancer diagnostics, and there are remarkable examples of their therapeutic
      applications. The future opportunities in both theoretical and practical
      oncoimmunology will directly depend on further advances in basic science.

PMID- 17514903
TI  - [Genome instability and oncogenesis].
AB  - Molecular alterations leading to genetic instability play a key role in tumor
      development. The basic reasons of genetic instability of tumor cells, i.e. up
      regulation of intracellular level of endogenous mutagens, in particular reactive
      oxygen spesies (ROS); decreased fidelity of DNA replication and chromosome
      segregation in mitosis; defects in DNA repair systems; and inactivation of cell
      cycle checkpoints preventing proliferation of abnormal cells are reviewed. In
      addition, tissue-specificity of tumorigenesis connected with genetic instability
      and development of new therapeutic approaches based on diminishing genetic
      instability or selective killing of neoplastic cells showing such defects are
      discussed.

PMID- 17514904
TI  - Tommy G. Thompson: advocating price transparency.

PMID- 17514906
TI  - Paving the way for medical banking.

PMID- 17514905
TI  - What's the latest word on [candidate's name here]-care?

PMID- 17514907
TI  - Independent dispute resolution process: no cure for the rate issue.
AB  - California's pilot independent dispute resolution process to resolve
      underpayments of noncontracted emergency services went into effect on Feb. 1.
      Unfortunately, it is a nonstarter for hospitals because it cannot establish the
      legal precedent that will settle how such services should be valued.

PMID- 17514908
TI  - When every penny counts.
AB  - The Medicare wage index factor has a significant impact on hospital revenue. Four
      strategies hospitals can incorporate to ensure the accuracy of their wage index
      schedules upon submission are: Work on the components of the wage index schedule
      throughout the year. Develop a wage index checklist/compliance work plan. Form an
      internal wage index committee. Establish processes for completing each
      component/line item on the wage index schedule.

PMID- 17514909
TI  - Financing the future III, Report 1. Healthcare payment: what would an ideal
      system look like?

PMID- 17514910
TI  - Growing the top line: 5 strategies to expand your business.
AB  - Five strategies healthcare executives can consider to enhance organic revenue
      growth are: Strategic communications. Physician referral development. Ambulatory
      and emergency care centers. Acquisitions and mergers. New hospital development.

PMID- 17514911
TI  - Acquiring physician-owned ambulatory businesses: traversing the minefield.
AB  - A hospital can acquire a physician-owned facility's assets or buy equity in the
      facility. The purchase price must fall within the bounds of fair market value. A
      professional services agreement also must reflect FMV. The purchasing hospital
      should determine whether the freestanding center should become a hospital
      outpatient department.

PMID- 17514912
TI  - Real option logic for healthcare entrepreneurial growth and survival.
AB  - Given the increasing market and technological uncertainty of capital investments,
      healthcare financial executives need to incorporate flexibility into their
      decision making. Traditional capital budgeting techniques do not take into
      consideration the need for flexibility, changes in the environment, or actions by
      management. In response, practitioners from various industries have adopted a new
      way of looking at capital investments: real options.

PMID- 17514913
TI  - A critical cause: 10 steps to improve CAH financial performance.
AB  - The 10 steps: 1. Develop a strategic planning process. 2. Develop a bed
      management strategy. 3. Design a revenue cycle management program. 4. Enhance
      Medicare payment. 5. Avoid the Medicare cash flow trap. 6. Develop effective
      pricing strategies. 7. Improve performance of clinics. 8. Manage labor and
      nonlabor resources. 9. Evaluate capital expenditures and needs. 10. Evaluate new
      products and services.

PMID- 17514914
TI  - How Medicare changes will affect your cardiovascular service line.
AB  - Evaluating the impact of Medicare changes on your organization's CV service line
      and formulating effective strategies are vital to the long-term stability of the
      program. Suggested methodologies include: Evaluating the impact of changes to DRG
      weights and payment. Evaluating the impact of cost-based payment. Evaluating
      product offerings using a portfolio model.

PMID- 17514915
TI  - Cardiac care: driving change--and stability.
AB  - Whether your facility's cardiac program is new or existing, maintaining a stable
      program requires that you: Challenge all assumptions. Monitor the competition. Be
      aware of threats posed by--and opportunities inimaging. Consider integrating
      cardiac and vascular services. Plan for succession. Accept the challenge of
      change.

PMID- 17514916
TI  - Key revenue cycle metrics.

PMID- 17514917
TI  - The other silos in healthcare organizations.

PMID- 17514918
TI  - Are you ready for HIPAA now?

PMID- 17514919
TI  - 5 steps to patient acquisition and retention.

PMID- 17514920
TI  - Outsourcing: the right move for your portfolio?

PMID- 17514921
TI  - Using technology adoption for growth projections.

PMID- 17514922
TI  - [Switzerland takes on obesity].

PMID- 17514923
TI  - [Psychological profile of obese patients].
AB  - The psychological profile of obese patients with binge-eating disorders is often
      characterized by decreased self-esteem, general dissatisfaction with life,
      impulsivity, phobias and hostility. So, it is not surprising that the association
      of obesity with binge-eating disorders is aggravated by the presence of psychic
      disorders, like depression, anxiety, bipolar disorders. A study conducted at our
      department on 150 obese patients with non-specific binge-eating disorders,
      clearly showed that about 75% of them presented a positive score in the self
      evaluation test for depression, nearly 60% suffered mild to very high anxiety,
      and about 50% had problems with self-affirmation.

PMID- 17514924
TI  - [Impulsivity--is one of the factors responsible for obesity?].
AB  - Obesity is a complex, multi-factorial condition involving biological,
      psychological and environmental (social and cultural) components. Among these,
      impulsivity seems to be of particular importance. Recently, Whiteside and Lynam
      have proposed to parse impulsivity into four separate dimensions: urgency, lack
      of premeditation, lack of perseverance and sensation seeking. Psychological tasks
      and questionnaires have been used to explore the cognitive and motivational
      mechanisms underlying the four facets of impulsivity in obese patients.

PMID- 17514925
TI  - [Weight changes in hyperthyroid patients: a challenge for clinicians?].
AB  - After the diagnosis of hyperthyroidism in patients, there is a search for a
      precise diagnosis as well as the prescription of a treatment according to its
      etiology. However a listing of symptoms and signs, present at the time of
      diagnosis, is seldom established. The weight history of the patient is almost
      always lacking in the medical records of hyperthyroid patient. By the time the
      patient has been treated after a few weeks or months, he often complains of
      weight gain. Thereafter the knowledge of the variations of the weight at the time
      of diagnosis will allow not only to get some insight in the psycho-social setting
      and the patient's habits, but also to deal with the critical time of the
      disappearance of hypermetabolism, linked to the hyperthyroid state, which could
      promote a weight gain.

PMID- 17514926
TI  - [Obesity and hypothyroidism: myth or reality?].
AB  - While obesity has been historically considered a criteria to establish the
      diagnosis of hypothyroidism, the association between them is seldom encountered
      in patients. Nowadays the main metabolic criteria is the gain of weight in the
      presence of other symptoms of hypothyroidism. The large differences between the
      thermogenesis of hypothyroid and hyperthyroid patients underline the complex
      relationship of thyroid hormones and metabolic pathways. The treatment of a
      subclinical hypothyroidism has almost no influence on the body weight, whereas in
      more severe dysfunctions a weight loss is expected, usually less than 10% of body
      weight. Thereafter severe obesity may not be secondary to a thyroid failure.

PMID- 17514927
TI  - [Micronutrition: a global approach for obese patients].
AB  - Micronutrition is proposed as a global approach for the obese person and aims at
      satisfying needs in micronutrients through a Mediterranean diet. This diet is
      associated with a personalized complementation if needed. First of all, a
      consultation in micronutrition consists of detecting possible deficits (iron,
      chromium, iodine, vitamins and mineral) with the means of patients history,
      questionnaires and, if needed, biological measurements. Micronutritional deficits
      are frequent in obese patients on restrictive diets. The balance in essential
      fatty acids (omega 3/6) and the content of essential amino acids (tryptophan) are
      crucial for the obese patients follow-up. Finally, intestinal flora seems to play
      an important role in the physiopathology in obesity.

PMID- 17514928
TI  - [A concept mapping study of nutritional knowledge in diabetic children and their
      parents].
AB  - This study describes, using concept mapping, the nature, organization of
      knowledge on nutrition and its evolution following therapeutic patient education
      program in 5 diabetic children (8 to 9 years old) and their mothers. Before the
      education session, mothers and children are highly knowledgeable about food. The
      organization of knowledge in children is conceptual and differs from that found
      in mothers which is based on problems solving. After education, new knowledge and
      new links between old and recent knowledge testify of learning. A comparison
      between the maps of children and their mother reveals similarities but also
      differences in their preoccupations. This research shows that using the
      preexisting knowledge networks of parents and children could contribute to
      improve their education on nutrition.

PMID- 17514929
TI  - [Current recommendations for the treatment of iron deficiency anemia].
AB  - Iron deficiency is a frequent complication in chronically ill patients and in
      pregnant women. Iron status can now be characterised precisely and relatively
      easily by determining serum ferritin, transferritin saturation and if necessary
      hypochromic erythrocytes and the haemoglobin content of erythrocytes (CHr). Oral
      iron replacement is usually restricted by limited absorption and low
      tolerability. Intravenous iron therapy is possible in such cases and can be
      combined with rHuEPO (e.g. EPREX/ epoetin alfa) in severe cases. Iron saccharate
      (VENOFER) is commercially available in Switzerland and this permits high dose
      iron replacement without any danger of anaphylaxis or acute iron toxicity.

PMID- 17514931
TI  - [Femoro-acetabular impingement].
AB  - Femur-acetabular impingement is a recently discovered etiology of early hip
      osteoarthritis. Patient history and clinical examination allow to make the
      diagnosis, whereas the radiological exams allow to find the etiology of
      impingement. Impingement is related to morphological alterations of the
      acetabular rim and/or proximal femur, leading to an abnormal contact between the
      articular components. The localisation of the abnormal morphology determines the
      type of impingement and the resulting articular damages. Because of the
      increasing risk of chondral lesions, only an early treatment may eventually
      improve the prognosis of the hip joint. If primary conservative treatment is
      unsuccessful in confirmed impingement cases, open or arthroscopic surgical
      treatment is indicated.

PMID- 17514932
TI  - [Somatic disorders, factitious disorders and simulation: the subtle art of
      differential diagnosis].
AB  - In every day practice, it is difficult, sometimes impossible, and always
      ethically delicate to determine the differential diagnosis between: disorders of
      a somatic nature, simulation and factitious disorders, as much for the
      psychiatrist as for the general practitioner in the front line. Our aim is to
      lead a reflection on this controversial theme on the basis of a clinical
      illustration.

PMID- 17514933
TI  - [Tamiflu, suicides and seasonal influenza].

PMID- 17514934
TI  - [Lessons of 70,000 death of the European canicula, 2003].

PMID- 17514935
TI  - [Euthanasia and French confusions].

PMID- 17514936
TI  - [Physicians, rich and poor ...].

PMID- 17514937
TI  - [The microscopic ordering and macroscopic disorder spectra analysis of X-band
      electronic paramagnetic resonance].
AB  - The correlation time and S order parameter are two important parameters to
      characterize the moving and distribution of the spin labeled macromolecule. It is
      significant to determine them simultaneously by lineshape analysis with an
      appropriate physics model for EPR spectrum analysis. In the present paper, the
      microscopic ordering and macroscopic disorder model (MOMD) was adopted to
      simulate the X-band EPR spectra of spin label with axial symmetric magnetic
      tensors. The experimental parameters were measured, and the divergence between
      the real values and the empirical values was analyzed. For MOMD spectra the
      authors proposed a criteria to select the experimental parameters. With the
      selected parameters, the correlation time and the internal S order parameter
      could be obtained simultaneously. And the valid range determined by the
      recognition function is presented.

PMID- 17514938
TI  - [Multi-spectral thermometry based on GA-BP algorithm].
AB  - Considering some defects of back-propagation neural network (BP), a new algorithm
      combining genetic algorithm (GA) with BP was described. The application of GA-BP
      to the data processing of multi-spectral thermometry was proposed. The simulation
      experiments, based on GA-BP algorithm and BP neural network respectively, show
      that the recognition precision of trained emissivity samples is +/-5 K and +/-10
      K respectively, and that of untrained emissivity samples is +/-10 K and +/-20 K
      respectively. No matter GA-BP algorithm or BP neural network is used, in general,
      the recognition precision of trained emissivity samples is higher than that of
      untrained emissivity samples. The recognition precision of true temperature is
      lower near the edge of sample sets. The GA-BP algorithm was more efficient than
      the BP neural network in the true temperature measurement.

PMID- 17514939
TI  - [A new measurement method of time-resolved spectrum].
AB  - A new method for measuring time-resolved spectrum (TRS) is brought forward.
      Programming with assemble language controlled the micro-control-processor
      (AT89C51), and a kind of peripheral circuit constituted the drive circuit, which
      drived the stepping motor to run the monochromator. So the light of different
      kinds of expected wavelength could be obtained. The optical signal was
      transformed to electrical signal by optical-to-electrical transform with the help
      of photomultiplier tube (Hamamatsu 1P28). The electrical signal of spectrum data
      was transmitted to the oscillograph. Connecting the two serial interfaces of
      RS232 between the oscillograph and computer, the electrical signal of spectrum
      data could be transmitted to computer for programming to draw the attenuation
      curve and time-resolved spectrum (TRS) of the swatch. The method for measuring
      time-resolved spectrum (TRS) features parallel measurement in time scale but
      serial measurement in wavelength scale. Time-resolved spectrum (TRS) and
      integrated emission spectrum of Tb3+ in swatch Tb(o-BBA)3 phen were measured
      using this method. Compared with the real time-resolved spectrum (TRS). It was
      validated to be feasible, credible and convenient. The 3D spectra of fluorescence
      intensity-wavelength-time, and the integrated spectrum of the swatch Tb(o-BBA)3
      phen are given.

PMID- 17514940
TI  - [Study of collisional broadening of spectral line by optical-optical double
      resonance].
AB  - The collisional broadening of the 2(1)sigma+ --> 6(1)sigma+ line of NaK molecule
      was studied using the optical-optical double resonance technique. A single-mode
      diode laser was set to a particular 1(1)sigma+ (v", J") --> 2(1)sigma+ (v',J')
      transition. Another single-mode diode laser was then used to excite the molecule
      from 2(1)sigma+ (v', J') level to the rovibrational level of 6(1)sigma+. The two
      laser beams counterpropagated through the cell. The broadening rate coefficient
      was determined from the slope of the total linewidth versus potassium density
      curve. The rate coefficient, k(br) = (1.4+/-0.7) x 10(-8) cm3 x s(-1), was
      obtained. The collisional excitation transfer between rotational levels of the
      2(1)sigma+ state [i. e., 2(1)sigma+ (v = 8, J = 12) --> 2(1)sigma+ (v = 8, J =
      13, 14)] was also investigated. The rates can be determined from the relative
      intensities of the main peak and satellite lines, combined with a rate equation
      model. The rates are 6.1 x 10(6) and 5.2 x 10(6) s(-1) respectively.

PMID- 17514941
TI  - [Establishment and melting of charge ordering in La0.3Ca0.7Mn(1-x)W(x)O3 system].
AB  - Polycrystalline samples of La0.3Ca0.7Mn(1-x)W(x)O3 (0.00 < or = x < or = 0.15)
      were prepared by conventional solid-state reaction method. The influence of W
      doping at Mn site on the magnetic transition of La0.3Ca0.7Mn(1-x)W(x)O3 system
      was studied by the measurements of magnetization-temperature (MT) curves,
      magnetization-magnetic intensity (MH) curves, and ESR spectra. The results show
      that, with the increase in W doping amount, the magnetic transition of the system
      exhibits a complicated charge process, when the doping amount is 0.00 < or = x <
      or = 0.08, the charge-ordering (CO) phase exists in the system, AFM/CO states
      coexist below the transition temperature, and the charge-ordering temperature
      (Tco) goes up with the increase in W doping content; when x > or = 0.12, the
      charge ordering (CO) state of the system weakens and melts, and paramagnetism
      ferromagnetism (PM-FM) transition exists at extremely low temperature.

PMID- 17514942
TI  - [Emitting characteristics and carrier composite regions variety of the blend of
      terbium complex and poly-n-vinylcarbazole].
AB  - A new rare earth complex TbGd(BA)6(bipy)2 was synthesized, which was used as an
      emitting material in electroluminescence. By doping with poly-N-vinylcarbazole
      (PVK), the stability and conductivity of terbium complex were improved. The
      photoluminescence of PVK, terbium complex and their blend indicated that energy
      transfer from PVK to terbium complex occurred. In the present paper, single-,
      double- and multi-layer devices were fabricated. In the double-layer devices,
      holes and electrons were recombined at the interface of emitting layer (EML) and
      electron transporting layer (ETL). With increasing the thickness of Alq3,
      especially at highly electric field, carrier composite region transferred closely
      to ETL. However, in multi-layer devices, carrier composite region was restricted
      at the interface of emitting layer and holes blocking layer (HBL) due to high
      HOMO level of BCP. Enhancing electric field, emission from terbium complex was
      getting saturation gradually and weak emission from PVK was observed. From the
      optimized multi-layer device, bright and green emission from terbium complex was
      obtained with the highest EL brightness of the device of 213 cd x m(-2) at 13.5
      V.

PMID- 17514943
TI  - [Hydrothermal preparation and luminescence of LaF3:Ce, Tb nano-sized phosphor].
AB  - Green-emitting LaF3:Ce, Tb phosphor nanoparticles were synthesized by a simple
      hydrothermal method and characterized by XRD, TEM and fluorescence spectra. The
      prepared samples had a hexagonal shape, fine size (30 nm), and high brightness
      under ultraviolet, and the structure of LaF3 remained unchanged after being doped
      with Ce3+ and Tb3+ ions. The blue Ce3+ emission centered at 261 nm is efficiently
      quenched in the samples of LaF3:Ce, Tb, in which the dominant emission is in the
      green at 544 nm, originating from the doped Tb3+ ions' transition of (5)D4 to
      (7)F5. Excitation spectra of the LaF3:Ce, Tb, observed at 544 nm, consist of both
      contributions from Ce3+ and Tb3+ ions. There is energy transfer of Ce3+ --> Tb3+
      in this system. The energy transfer mechanism was discussed. Above all, the
      phosphor nanoparticles have high photoluminescence intensity even without any
      calcination, about twice that of bulk materials prepared by high temperature
      solid synthesis, and the intensity is also stronger than calcined phosphor
      nanoparticles.

PMID- 17514944
TI  - [Effect of PEG400 on the luminescent Eu(BA)3/SiO2].
AB  - Rare earth organic complexes combined with inorganic compounds can enhanced
      thermal stability, but inorganic compounds matrix has great influence on the
      luminescence characteristic of rare earth organic complexes. The luminescence
      characteristic of organic and inorganic compound material was improved by PEG
      doping in the material. Eu(BA)3/SiO2 and Eu(BA)3/PEG400-SiO2 were synthesized by
      Sol-Gel method. The result of luminescence analysis showed that the excitation
      spectra and emission spectra of Eu(BA)3 accorded with those of Eu(BA)3/SiO2 and
      Eu(BA)3/PEG400-SiO2, but the luminescence intensity of Eu(BA)3/SiO2 was improved
      by PEG400-SiO2 in SiO2 gel. This was because PEG400 as a hard Lewis base, could
      be combined with rare earth ion and increase the luminescence intensity of
      Eu(BA)3. It was shown that the amount of PEG400 in Eu(BA)3/SiO2 had influence on
      luminescence intensity of Eu(BA)3, namely there was better luminescence intensity
      in Eu(BA)3/SiO2 with increment of the PEG400 addition, but when the amount of
      PEG400 exceeded 50 wt% of that of SiO2, the luminescence intensity of Eu(BA)3
      hardly increased. When the amount of PEG400 exceed 15 wt% of that of SiO2, PEG400
      had little influence on the content of water and hydroxy in the matrix, as
      verified by IR spectrum. The surface characteristic of SiO2 gel was investigated
      by atomic force microscopy (AFM).

PMID- 17514945
TI  - [Luminescence properties of white LED blue light conversion materials].
AB  - Using rare earth oxides as raw materials, yttrium aluminum garnets activated by
      cerium and gadolinium ions were prepared by high energy ball milling and solid
      state reaction at 1300 degrees C. The crystal structures of the products were
      studied by XRD, and the luminescence characteristics of Ce ion and the influence
      of Gd ion were studied by emission and excitation spectra. The results indicated
      that the products were yttrium aluminum garnet crystals of cubic system, and they
      were excited by blue light chips effectively. The emission peak of phosphors
      could change among 530-560 nm by adjusting the mole density of doping ions. The
      red shift of emission spectra could be interpreted with the configuration
      coordination figure. White LEDs were fabricated by phosphor conversion. When
      electric current is 20 mA, and the working voltage is 3.5 V, the white light LED
      chromaticity coordinates are x=0.310 and y=0.323, the lumen efficiency is 26.131
      m x W(-1), the color rendering index is 81.8, and the color temperature is 6605
      K.

PMID- 17514946
TI  - [Study on electro-optical performance of frequency driven liquid crystal light
      valve].
AB  - The electro-optical characteristic and principle of frequency-driven liquid
      crystal light valve were discussed and analyzed. Under different electric field
      frequency and certain AC voltage, the electro-optical characteristic of frequency
      driven TB3639 liquid crystal light valve was measured. The results show that it
      can display gray scale in visible light region, and it can not only display black
      and white, but also can display different gray scale. The influence of frequency
      driven way to the transmission spectrum change tendency of different wavelength
      in visible light is approximately same, which will avoid high chromatism in
      application. The new frequency-driven liquid crystal light valve can improve
      display quality of liquid crystal display device. It will develop new application
      of liquid crystal display device and has practical application value.

PMID- 17514947
TI  - [Ion-conducting mechanism of composite polymer electrolyte: an emission FTIR
      spectroscopy study].
AB  - Solvent-free, composite electrolytes based on poly(ethylene oxide) (PEO) were
      prepared by using mesoporous silica SBA-15 with surface modification of
      (trimethylchlorosilane) as the filler. The samples were explored by emission FTIR
      spectroscopy at elevated temperatures. The results of emission FTIR spectra
      illustrated the dependence of crystalline PEO phase on temperature. On the basis
      of electrochemistry, SEM, and emission FTIR studies, the effect of inorganic
      filler on the ionic conductivity was analyzed, and a conclusion concerning the
      ion-conducting mechanism of composite polymer electrolyte was drawn. The
      exploratory experiments demonstrated that the emission FTIR spectroscopy is an
      important method to be applied in the study of lithium batteries.

PMID- 17514948
TI  - [The identification of several saturated fatty acids and their salts by means of
      infrared spectrometry].
AB  - It is considered that saturated fatty acids and their salts may be potential
      hydrocarbon-generation matters in carbonate rocks. However, there is no effective
      method to distinguish them from natural sediments, making recognizing their
      distribution in sediments a challenge. Formic acid, acetic acid, stearic acid,
      calcium formate, calcium acetate, magnesium acetate, calcium stearate, and
      magnesium stearate from some chemical plants were investigated by means of
      Fourier transform infrared spectroscopy. Their infrared spectra were obtained and
      the distinctions of the infrared spectra between saturated fatty acids and their
      salts were studied in detail. The differences in the group's electron-releasing
      ability, molecular reduced mass, ion configuration and the length of carbon chain
      can cause wavelength shifts of infrared absorption peaks of the saturated fatty
      acids and their salts. The research provides a method for the identification of
      saturated fatty acids and their salts in samples from nature.

PMID- 17514949
TI  - [Application of IR spectrum to the research on coordination mechanisms of organic
      carboxylic acid during homogeneous precipitation].
AB  - Infrared (IR) spectrum, X-ray diffraction (XRD) and transmission electron
      microscope (TEM) were used to study and characterize the coordination mechanisms,
      products and morphology of organic carboxylic acid during homogeneous
      precipitation in the system of Ce(NO3)2 x 6 H2O and urea solution. The results
      showed that monocarboxylic acid stearic acid played a role of surfactant, and the
      product was still orthorhombic Ce2O(CO3)2 x H2O with a high crystallization
      degree. In turn, duality-carboxylic acid tartaric acid and tri-carboxylic acid
      citric acid were combined with Ce3+ to form chelate citric acid and cerium
      tartaric acid, respectively. The results were caused by different mechanisms of
      reaction in the solution.

PMID- 17514950
TI  - [Infrared spectroscopic studies of the effect of hydrotalcite on the capability
      of agricultural film].
AB  - Different kinds of hydrotalcite and their effects on the optic capability,
      transmittance, infrared anti-transmittance and heat preservation of agriculture
      film were studied by IR spectroscopy. It was found that the haze degree of the
      film decreased about 1.5% because the diameter of the hydrotalcite made in Dalian
      was bigger than those made in Japan. Compared to the french chalk, the
      hydrotalcite had much better capability of infrared anti-transmittance. But from
      the spectra of hydrotalcite, whichever made in Dalian or in Japan, there was no
      infrared absorption in the region of 1100-1200 cm(-1). Compared with the
      wavelength of 9-11 microm, the absorbance band at 1360 cm(-1) had a little shift.
      Hence, the capability of heat preservation of hydrotalcite-added agriculture film
      would be studied in the future work.

PMID- 17514951
TI  - [Influence of LPLS algorithm parameters on NIR veracity].
AB  - The theory of local partial least square (LPLS) algorithm was described based on
      locally weighted regression algorithm (LWR). The influence of data processing
      parameters, such as principal component numbers and local set-up sample number in
      LPLS mode, on the NIR veracity was studied with homemade grating diffuse NIR
      instrument using Yunnan flue-cured tobacco. Results showed that for nicotine
      model, the principal component number decided by cross validation was not the
      best choice, and better results could be achieved by reducing the principal
      component number; using 30-50 samples to set up NIR model, the veracity of total
      sugar, total nitrogen, and nicotine could be improved by 7%, 14% and 10%,
      respectively. So, LPLS algorithm can effectively improve NIR model's veracity,
      and is a good method to set up robust NIR models.

PMID- 17514952
TI  - [Structure analysis of benzoic medicines by near infrared and two dimensional
      correlation spectroscopy].
AB  - The structure analysis of benzoic medicines by Fourier transform near infrared
      spectroscopy and generalized two dimensional correlation spectroscopy was
      performed. Three kinds of medicines showed unconspicuous changes in one
      dimensional near infrared spectra, while the two dimensional correlation spectra
      showed high resolution, and were more explicable. By the comparison and analysis
      of raw near infrared spectra and 2D-correlation spectra, the near infrared
      absorption peaks of benzoic acid medicines were assigned, and their structure
      characteristics were analyzed, the results affirmed the six-membered ring
      intramolecular hydrogen bond especially. The study is helpful to the in-depth
      understanding of benzoic medicines, and provides information for the future study
      and utilization of benzoic medicines.

PMID- 17514953
TI  - [Study on the relation between ginkgolide B and water by FTIR].
AB  - The method of IR was used to study GB spectrum variety with different water
      ratio, and it was showed that GB IR spectrum only changed in the absorption
      strength at 3452, 1793, 1780 and 1630 cm(-1). The reason is that the water was
      concealed by GB cage skeleton and formed hydroxyl bond with GB hydroxyl groups,
      and the structure of GB remained unchanged and accorded with standardized GB.
      With the help of DSC and LC-MS, the subtle relations between GB and water were
      explained, GB is lipophilic and can not be dissolved by water, but in general, GB
      is easy to absorb the water of environment, and can be dehydrated under
      particular conditions.

PMID- 17514954
TI  - [Prediction of maize stover components with near infrared reflectance
      spectroscopy].
AB  - The components concentrations in maize stover were analyzed with 67 samples
      selected from 380 samples of different provinces and varieties in order to serve
      the biomass utilization of our country. The technique of near infrared
      reflectance spectroscopy (NIRS) and partial least square (PLS) regression were
      used to establish the models. The results showed that the calibration models
      developed by the spectral data pretreatment of the first derivative+Karl Norris
      derivative filter were the best for ash, hemicellulose, cellulose, Klason lignin,
      acid unsolvable ash, and water in the spectral region of 4100-7500 cm(-1). The
      root mean square error of cross validation (RMSECV) for the above six components
      was 0.991, 1.27, 1.44, 0.599, 0.0903 and 0.547, respectively; the root mean
      square error of prediction (RMSEP) was 0.7746%, 1.8072%, 0.2569%, 2.5819%,
      0.5158% and 1.0325%, respectively. The models can be used to measure various
      samples in biomass transformation industry.

PMID- 17514955
TI  - [Application PCA-ANN method to fast discrimination of tea varieties using
      visible/near infrared spectroscopy].
AB  - A new method for the discrimination of varieties of tea by means of visible/near
      infrared spectroscopy (Vis/NIRS) (325-1075 nm) was developed. A relation has been
      established between the reflectance spectra and the tea varieties. The data set
      consists of a total of 150 samples of tea. First, the data was analyzed with
      principal component analysis (PCA). It appeared to provide the reasonable
      clustering of the varieties of tea. Meanwhile PCA compressed hundreds of spectral
      data into a small quantity of principal components which described the body of
      the spectra; the first 6 principal components computed by PCA were applied as
      inputs to a back propagation neural network with one hidden layer. One hundred
      twenty five samples from five varieties were selected randomly, then they were
      used to build BP-ANN model. This model has been used to predict the varieties of
      25 unknown samples; the residual error for the calibration samples is 1.267 x 10(
      4). The recognition rate of 100% was achieved. This model is reliable and
      practicable. So this paper could offer a new approach to the fast discrimination
      of varieties of tea.

PMID- 17514956
TI  - [Application of HATR-FTIR spectroscopy to the analysis of quality mensuration of
      rhizoma Atractylodes].
AB  - The present paper used many kinds of mensuration of FTIR spectroscopy to
      determine traditional Chinese drugs--rhizoma atractylodis macrocephalae.
      Comparing the horizontal attenuated total reflection-Fourier transform infrared
      spectra (HATR-FTIR) of xylem and outer layer parts of cuticle indicates that
      there are more butenolide and its derivatives in outer layer parts of cuticle.
      Much more chemical materials could be found in fresh sample than in drying
      sample, possibly due to the decreased amount of naphtha in the drying sample. The
      HATR-FTIR of xylem of rhizoma atractylodis macrocephalae and its confusable
      varieties were transformed into second derivative FTIR to make sure whether the
      peak location is consistent. As a result, the difference is significant.

PMID- 17514957
TI  - [The spectrum characterization of non-stoichiometry potassium lithium niobate
      crystals].
AB  - A batch of potassium lithium niobate (KLN) crystals with different compositions
      were grown by using TSSG technique. Samples with three different compositions
      were well polished. By using near infrared cw:Ti-sapphire laser, their Second
      Harmonic Generation (SHG) properties were investigated. The results showed that
      the SHG effect is related to the composition of the samples, and their frequency
      doubling efficiency enhanced with the raise of Li ions content in the crystal. By
      using infrared Raman technique, the properties of nonlinear lattice vibration of
      thee samples were investigated, and the character of Raman spectrum were
      analyzed, as well the effect of composition on the SHG properties were discussed.
      The analysis results showed the striking effects of Li content for these Raman
      peaks. For KLN sample with small Li content, the three character peaks belonged
      to [NbO6]7- octahedron show simple peak. With the raise of Li content in crystal,
      the peaks belonged to v2 mode were partly split, and the peak belongs to v5 mode
      was broadened. When the Li content approach to the chemical composition KLN
      crystal, and the structure of [NbO6]7- octahedron is almost to be disorganized,
      the peaks belonged to v5 mode were split, and the peaks belonged to v1 mode and
      v2 mode were partly split also, with more distinct weak peaks in the wavelength
      range of 100-400 cm(-1). These effects were caused by the raise of Li content,
      which leads to the severer aberrance of [NbO6]7- octahedron in KLN crystal, and
      disturbing the lattice vibration of the octahedron. This phenomenon is agreed
      with the nonlinear properties of potassium lithium niobate crystal.

PMID- 17514958
TI  - [Raman spectra analysis of DKDP crystal].
AB  - Based on the space group theory, the normal vibration modes of DKDP crystal were
      analyzed and the assigned. Raman spectra were measured at the room temperature.
      Results show that the lattice vibration spectra of DKDP arise mainly from the
      internal vibrations of D2PO4(-) anionic cluster. Compared with the Raman spectra
      of an aqueous solution of KH2PO4 and an NaD2(PO4)2 crystal, the four internal
      vibration models of the D2PO4(-) in DKDP were assigned as 881 cm(-1) (v1), 357
      cm(-1) (v2), 514/541 cm(-1) (v3), 965 cm(-1) (v4), respectively.

PMID- 17514959
TI  - [Study of human tumor tissues by Raman imaging spectra].
AB  - The Raman mapping spectra were collected from the samples of fresh human breast
      tumor tissues with the excitation wavelength at 633 nm, their correlation
      coefficients with the reference spectra of chemical DNA, cytoplasm and extra
      cellular matrix etc. were calculated, and the images were created based on these
      correlation coefficients. Examining these images, the authors found that they
      show approximately the distribution of the corresponding reference chemicals in
      human tissues and that the DNA spectrum correlation images reflect the DNA
      distribution quite well because of its much lower correlation with the spectra of
      other morphological chemicals. This work is helpful in understanding the
      chemical/morphological basis of the breast tissue Raman spectra and in developing
      the Raman diagnostic method for breast tumor.

PMID- 17514960
TI  - [Comparative study on SERS and stability of negative silver colloids].
AB  - Negatively charged colloidal nano-silver particles were prepared by the colloidal
      chemical method. A 1.7% solution of silver nitrate (2 mL) was diluted with
      deionized water to 100 mL. A 1% solution of tannic acid (1 mL) was added dropwise
      to the solution stirring, then a 1% solution of potassium carbonate anhydrous (3
      4 drops) was added to the mixed solution. Finally, a red-brown silver sol was
      obtained. It was testified that the silver sol is a negatively charged colloid by
      experiment of electrophoresis. The negative silver colloids (for short, old NCS)
      were kept on at the room temperature two year ago in order to test its SERS and
      stability. The sizes of particles were determined by Hitachi H-800 transmission
      electron microscope. Absorption spectroscopy and SERS were used to determine the
      main properties. Absorption spectra were obtained with UV-2401PC. Raman spectra
      were recorded with RENISHAW MIK 2000 Raman micro-spectroscopy. The 514.5 nm line
      of an argon ion laser with about 3 mw was used. Compared with the newly prepared
      negative silver colloids (for short, new NCS). It was found that the mean
      diameter of the old NCS was larger than the new NCS; old NCS had absorption
      maximum at 431 nm but new NCS at 418 nm, the absorbance spectrum of old NCS had a
      12 nm red shift, and the red shift rate is about 0.5 nm/month; Both strong SERS
      spectra were observed when cationic molecules of fuchsine basic and neutral
      molecules of alcidine orange adsorbed on old NCS and new NCS. For cationic
      molecules of methylene blue, the SERS is stronger on new NCS than old NCS; but no
      SERS was observed for the anionic molecule of benzoic acid both on new NCS and on
      old NCS.

PMID- 17514961
TI  - [Synthesis and DNA binding spectroscopic studies of Cu(II)-HAsp-Im complexes].
AB  - Two novel complexes of [Cu(HAsp)ImH2O]SO4 x 4 H2O and [Cu(Asp)Im(OH)] x 4 H2O
      (HAsp = Aspartic acid molecule, Asp = Aspartic acid ion, Im = Imidazole) were
      synthesized and characterized by elemental analysis, IR spectroscopy and TG-DTA.
      The interactions of the complexes with sperm DNA were studied by electronic
      absorption and fluorescence spectra. Results showed that the reactions of the two
      complexes with DNA are obviously different: for [Cu(HAsp)ImH2O]SO4 x 4 H2O, it is
      intercalation companied by electrostatic effect, while [Cu(Asp)Im(OH)] x 4 H2O
      mainly cooperates with the nitrogen atom of the DNA base pair, which induces the
      breakage of DNA double helix. The reasons for these differences in their DNA
      binding modes were also discussed.

PMID- 17514962
TI  - [Study on the interaction between BSA and nicotine].
AB  - The interaction of BSA and NIC was investigated by absorption spectra,
      fluorescence spectroscopy and synchronous fluorescence spectroscopy. In the
      system of sodium phosphate dibasic-citric acid of 0.1 mol(-1) x L(-1),
      fluorescence titration showed that the fluorescence intensity of BSA at 342 nm
      was quenched when NIC was added, NIC was capable of binding with BSA to form a
      1:1 complex and the quenching mechanism of BSA affected by NIC was shown to be a
      static quenching procedure by calculating the binding number n and binding
      constant K. NIC decreased the intensity of the characteristic absorption peak of
      BSA, showing that the binding of NIC to BSA had strong impact on protein
      conformation with the decrease in a-helical content of the protein. Synchronous
      fluorescence indicated that the binding of NIC to BSA is near tryptophan subunit.

PMID- 17514963
TI  - [Interaction of tributyltin (TBT) compound and bovine serum albumin (BSA)].
AB  - Tributyltin (TBT) compound is one of the main components of antifouling paint for
      boats and ships. The interaction of TBT compound and bovine serum albumin (BSA)
      was investigated by ultraviolet, fluorescence and circular dichroism (CD)
      spectra. The influences of concentration, acidity and organic solvent were also
      studied. The results showed that the interaction of TBT and BSA was dual, showing
      not only the hydrophobic actions of butyl groups but also the coordination action
      of tin cation with BSA molecule, which resulted in the exposures of aromatic
      amino acids residues of tryptophane and tyrosine in BSA molecule, the destruction
      of BSA secondary structure, the decrease in alpha-helix content, and the
      transformation of the conformation.

PMID- 17514964
TI  - [Spectroscopic study on the binding of Mn(II) to EHPG].
AB  - Under the conditions of 0.05 mol x L(-1) Hepes buffer at room temperature and pH
      7.4, the interaction of ethylene-N,N'-bis(o-hydroxyphenylglycine) (EHPG) and
      Mn(II) was investigated by both fluorescence and UV difference spectra. Results
      showed that the molar ratio of the complex is 1:1. With the addition of manganese
      ions, the fluorescence peak of EHPG at 310 nm decreased, while the peaks of UV
      absorptivity at 238 and 291 nm increased. The molar absorptivity of Mn(II) to
      EHPG at 238 nm is (1.31 +/- 0.02) x 10(4) cm(-1) x mol(-1) L. The disassociation
      constant for Mn-EHPG was determined to be (1.36 +/- 0.21) x 10(-5). It can be
      concluded that the binding of Mn(II) to EHPG is not a strongly binding reaction.

PMID- 17514965
TI  - [Study on the interaction between alginic sodium diester and azur A and the
      application].
AB  - The interaction of alginic sodium diester (ASD) and azur A (AA) was studied by
      absorption spectra. The influence of pH and the molar ratio of AA/ASD on the
      spectra was investigated. The maximum binding number (N = 168) and the binding
      equilibrium constant (K = 3.25 x 10(6)) of the alginic sodium diester and azur A
      were obtained by the theoretical model. The new method for the determination of
      ASD was developed by the formation of ASD-AA ion-association complex that caused
      the fading of the AA. The detection limit is 0.009 microg x mL(-1). The method
      has the advantages of simplicity, stable system, good accuracy and selectivity,
      and was applied to the determination of alginic sodium diester in tablets with
      satisfactory results.

PMID- 17514966
TI  - [Spectroscopic study on the effect of crystallization of the hydroxyapatite on
      the secondary structure of bovine serum albumin].
AB  - The effect of crystallization of hydroxyapatite on the secondary structure of
      bovine serum albumin (BSA) was studied by circular dichroism spectrum, Fourier
      transform infrared spectroscopy, derivative, deconvolution and curve-fitting
      techniques in the present paper. The CD results show that pure bovine serum
      albumin is composed of 56.8% alpha-helices, 5.8% beta-sheets, 14.1% beta-turns
      and 23.9% random structures, while the bovine serum albumin in the
      Ca10(PO4)6(OH)2/bovine serum albumin solution is composed of 25.4% alpha-helices,
      25.0% beta-sheets, 20.0% beta-turns and 29.7% random structures. The results of
      Fourier transform infrared spectroscopy are in good agreement with those from the
      CD spectra. From these results it can be seen that the percentage of alpha-helix
      decreased, while that of the beta-sheet increased with the formation of the
      crystal of hydroxyapatite, and with the reaction time increasing, the percentages
      of alpha-helix obviously dropped and those of beta-sheet markedly rose. These
      results showed that alpha-helix transformed into beta-sheet. Furthermore the
      essence of these changes is discussed.

PMID- 17514967
TI  - [Ultraviolet-visible absorption spectral properties of Sudan III in different
      solvents].
AB  - Ultraviolet-visible absorption spectral properties of Sudan III in different
      solvents were studied. The results show that the main absorption peaks are
      located in 200-230 nm, 340-360 nm and 490-510 nm. When Sudan III is in polar
      solvent, two absorption peaks appear in the mid-ultraviolet region, 200-230 nm.
      And when it is in nonpolar solvent, the absorption changes from two peaks to one
      peak with the concentration of Sudan III increasing. When it is in composite
      solvent, the two absorption peaks disappear, but one absorption peak appears at
      310 nm. Molar absorptivities of Sudan III in the five solvents were determined,
      whose order of magnitude was 10(4).

PMID- 17514968
TI  - [The spectroscopic study on the interaction between edible pigment and human
      serum albumin in two-phase aqueous systems].
AB  - In polyethylene glycol 2000 (PEG)-(NH4)2SO4-edible pigment two-phase aqueous
      systems, the spectroscopic behaviour of the complexes of edible pigment and human
      serum albumin in PEG phase was investigated. Effects of different acidity,
      quantities of PEG and salt, reaction time, and coexistent matter on the
      determination of systems were discussed. Experimental results show that compared
      to BS spectra, the maximum wavelength of the complex of human serum albumin
      shifted to the red by 13 nm in buffer solution at pH 8, the maximum binding
      number of 40 was measured by molar ratio method, and the apparent molar
      absorptivity was 9.4 x 10(4) L x mol(-1) x cm(-1). The linear range was 0-21.07
      mg x L(-1). With different surfactant, the interaction mechanism of protein and
      edible pigment was discussed.

PMID- 17514969
TI  - [Study on fluorescence property of DCM with SDS in water solution excited by 532
      nm laser].
AB  - The fluorescence property of DCM in water solution with added different
      concentration of SDS is reported. With increasing the concentration of SDS in
      water, the solubility of DCM and the fluorescence intensity increase. When the
      concentration of SDS increases from 0.025 to 0.5 mol x L(-1), the maximum
      fluorescence relative intensity is enhanced by a factor of 95. A powerful dye
      laser at wavelength of 648 nm was generated in the solution of DCM in water with
      SDS exited by a 532 nm laser. It shifts 13 nm compared with the dye laser
      wavelength of the solution of DCM in ethanol. And enhancement of SRS of C6H6 was
      achieved both in the solution of DCM in water with SDS and in the solution of DCM
      in ethanol. The result is that the second, the third and the fourth order Stokes
      of C6H6 are all enhanced. But the former mainly enhances the fourth order Stokes
      (632 nm) and the enhancement gain coefficient is 8.5, while the latter mainly
      enhances the third order Stokes (595 nm) and the enhancement gain coefficient is
      2.5. The mechanism of solubility, fluorescence enhancement and its possible
      application are discussed.

PMID- 17514970
TI  - [Synthesis, characterization and fluorescence property of an unsymmetrical Schiff
      base and its copper complex].
AB  - An unsymmetrical tetradentate Schiff base ligand (H2L) was synthesized using 5
      chloro-2-hydroxybenzophenone, o-phenylenediamine and salicylaldehyde. A solid
      complex of this ligand CuL was prepared and characterized by elemental analyses,
      IR spectra, UV spectra, TG-DTG and molar conductance. Possible structure of this
      complex was proposed. The fluorescence property of the ligand and complex was
      also studied. The result indicates that the Schiff base reagent exhibits a
      maximum of fluorescence emission spectrum at 385 nm. At pH 9.62, the copper
      complex of this reagent can cause fluorescence quenching of the reagent.

PMID- 17514971
TI  - [A fluorescence quenching method for the determination of trace chlorite in water
      with rhodamine B].
AB  - In acidic sodium acetate-HCl buffer solution containing KI, Rhodamine B (RhB) has
      a fluorescence peak at 580 nm. When ClO2(-) exists fluorescence quenching occur.
      The fluorescence quenching intensity is linear with the concentration of ClO2(-)
      in the range of 0.0218-0.51 microg x mL(-1). Based on this, a new, simple,
      sentisive fluorescence method has been proposed for the determination of ClO2(-)
      in water, with satisfactory results.

PMID- 17514972
TI  - [Fluorescence spectra of Dichroa febrifuga aqueous extraction].
AB  - Fluorescence spectra of chang shan (Dichroa febrifuga Lour) aqueous extraction
      were studied. In the three-dimensional fluorescence contour spectrum, three
      fluorescence peaks of quinazoline alkaloids, which are the active components of
      chang shan, were observed. The excitation wavelengths of the peaks were 235, 270
      and 320 nm, respectively, and the emission wavelength of all the peaks was 430
      nm. Three-dimensional fluorescence contour spectrum is the very image of
      fingerprint, suitable for qualitative identification of traditional Chinese
      medicine. In the range of pH 3 to pH 6, the fluorescence spectrum of chang shan
      aqueous extractions changes with the variation in pH value. The reason for this
      spectral change might be the protonation of N-1 in quinazolone ring of beta
      dichroine (febrifugine) molecule. There is an excellent linear relationship
      between the fluorescence intensity and the concentration of chang shan under
      nearly neutral conditions, thereby a quantitative method for the determination of
      quinazoline alkaloids may be established.

PMID- 17514973
TI  - [Study on the role of polysaccharide and flavone in Chinese herbs in protecting
      DNA with fluorescence probe].
AB  - The aim of the present work is to study the role of polyaccharide and flavone
      compounds of Flos lonicerae, Ganoderma lucidum etc. in protecting DNA with EB as
      a probe to determine the fluorescence integration intensity of DNA and EB
      mixture. D is defined as the interaction constant between different extracts from
      traditional Chinese herbs and DNA. The bigger the D, the stronger the interaction
      of drugs and DNA. According to the definition of D, the impact of polysaccharide
      and flavone compounds on the protection of DNA is discussed. The results show
      that all the extracts from traditional Chinese herbs can interact with DNA, but
      the degree of interaction is different. The order is as follows: folium hippophae
      rhamnosides > rhizoma anemarrhenae > radix acanthopanacis senticosi > Ganoderma
      lucidum > radix achyranthis bidentatae > fructus lycii > Flos lonicerae > rhizoma
      atractylodis > Astragalus membranaceus > Flos chrysanthemi in the presence of
      polysaccharide compounds, while folium hippophae rhamnosides > Flos lonicerae >
      fructus lycii > rhizoma atractylodis > Astragalus membranaceus > rhizoma
      anemarrhenae > radix acanthopanacis senticosi > Ganoderma lucidum > radix
      achyranthis bidentatae (Flos chrysanthemi, with no signals) in the presence of
      flavone compounds.

PMID- 17514974
TI  - [Rapid simultaneous analysis of fluorene, carbazole, benzo[a]pyrene, and perylene
      by derivative-constant energy synchronous fluorescence spectroscopy].
AB  - A new method of derivative constant-energy synchronous fluorescence (CESF)
      spectroscopy for the simultaneous determination of fluorene, carbazole,
      benzo[a]pyrene and perylene was developed. The comparison and explanation of its
      performance are presented. The derivative CESF spectra are apparently more
      structured than the direct CESF. The scanning of derivative CESF is more
      effective than derivative constant-wavelength synchronous fluorescence
      spectroscopy. By using this method, real samples (tap water, seawater and
      airborne particulates) were determined directly and good results were obtained.
      The recoveries in tap water, seawater and airborne particulates were 90.0%
      108.0%, 90.0%-104.0% and 90.0%-102.0% respectively.

PMID- 17514975
TI  - [Simultaneous spectrophotometric determination of certain beta-lactam antibiotics
      in rabbit serum using multivariate calibration methods].
AB  - Cefuroxime sodium, ceftriaxone sodium, cefotaxime sodium and cefazolin sodium
      have absorption in ultraviolet region, and their absorption spectra are
      overlapping. So they can not be determined individually by spectrophotometry
      without prior separation. In this paper, the chemometric multivariate calibration
      method was applied to the simultaneous determination of these four compounds in a
      Britton-Robinson buffer solution (pH 2.09), and the analytical results were
      compared with those by classical least squares (CLS), principal components
      regression (PCR) and partial least squares (PLS). The linear ranges of cefuroxime
      sodium, ceftriaxone sodium, cefotaxime sodium and cefazolin sodium are 1.0-20.0,
      2.0-20.0, 2.0-20.0 and 1.0-18.0 microg x mL(-1), respectively. The proposed
      procedure was successfully applied in the determination of these drugs in rabbit
      serum, and the result obtained from spectrophotometry was compared with the one
      by HPLC with no significant difference found.

PMID- 17514976
TI  - [Study on solid phase extraction and spectrophotometric determination of
      palladium with MCI-GEL resin].
AB  - Based on the color reaction of 2-(2-quinolinylazo)-5-diethylaminoaniline (QADEAA)
      with palladium(II) and the solid phase extraction of its colored complex with MCI
      GEL reversed phase cartridge, a new method for the determination of trace
      palladium was established. In the presence of 0.2-2.0 mol x L(-1) of hydrochloric
      acid solution and CTMAB medium, QADEAA reacts with palladium(II) to form a stable
      2:1 complex. The colored complex can be enriched by MCI-GEL reversed phase
      cartridge, and the retained chelates was then eluted by acetone. The eluant was
      determined by spectrophotometry at 615 nm. Beer's law is obeyed in the range of
      0.01-1.5 mg x L(-1). This method was applied to the determination of palladium
      with good results.

PMID- 17514977
TI  - [Spectrophotometric determination of codeine through charge-transfer reaction].
AB  - The charge-transfer reaction of 7,7,8,8-tetracyano-quinodimethane (TCNQ) as a pi
      electron acceptor with codeine as electron donors was investigated by
      spectrophotometry. TCNQ was found to react with codeine to produce stable charge
      transfer complexes in acetone. Meanwhile, the studied drugs suffer a considerable
      bathochromic shift (from 216 to 843 nm). The influential factor of charge
      transfer reaction and the optimum conditions for the determination of codeine
      were investigated in detail. Therefore a simple, rapid and accurate method with a
      good selectivity for the determination of codeine has been developed. The results
      show that Beer's law is obeyed in the ranges 0.1-1.6 microg x mL(-1) for codeine.
      The apparent molar absorptivity of the complex at 843 nm is 1.7 x 10(4) L x mol(
      1) x cm(-1). Furthermore, the association constants and standard free energy
      changes were studied, and the mechanism of charge-transfer reaction was explored
      elementarily. The proposed method has been applied successfully to the
      determination of codeine in pharmaceutical preparations. The recoveries are from
      (98.94+/-0.96)% to (99.12+/-1.21)%.

PMID- 17514978
TI  - [Characterization and heavy metal adsorption properties of schwertmannite
      synthesized by bacterial oxidation of ferrous sulfate solutions].
AB  - An amorphous ferric hydroxysulfate named schwertmannite was synthesized by using
      bacterial oxidation of ferrous iron by resting A. ferrooxidans cells in acid
      ferrous sulfate solution (pH 2.5). The identification of the bacterially oxidized
      iron precipitate was carried out by SEM, XRD, FTIR and chemical analysis. Results
      showed that resting cells of A. ferrooxidans LX5 could completely oxidize ferrous
      ions to ferric ions in the FeSO4-H2O system after 2 days of incubation. The
      solution pH decreased from an initial 2.5 to 2.10, and about 15% of the ferrous
      iron was transformed into the red-brown precipitates. The subsequent
      characterization of the precipitates showed that the biotic, synthetic ferric
      hydroxysulfate was schwertmannite. Sorption edge measurement showed that the
      adsorption behavior of metal cations (e. g., Cu2+, Zn2+ and Cr3+) was pH
      dependent. The adsorption increased with an increase in pH, and the maximum was
      found in a pH range of 6.0-7.0. For solution concentration of 50 mg x L(-1), the
      maximum adsorption efficiencies of Cu2+, Zn2+ and Cr3+ were 99.3%, 99.4% and
      87.6%, respectively.

PMID- 17514979
TI  - [Analysis of trace elements in corn stover by ICP-AES].
AB  - The contents of trace elements of Zn, Mg, Mn, Sr, Fe, Co, Ni and Se in the corn
      stover collected from Shanxi, Beijing, Xinjiang, Shandong, Neimeng, Gansu,
      Shaanxi, Jilin, Yunnan and Jiangsu, 10 different provinces in China, were
      determined by ICP-AES using nitrifying method of high pressure nitrifying pot.
      This method proved to be easily operational, rapid, highly sensitive, and
      accurate, and can be adopted as the method of determining many elements
      simultaneously. The recovery yields of Zn, Mg, Mn, Sr, Fe, Co, Ni and Se are
      96.55%-103.8%, 98.0%-102.5%, 95.7%-104.1%, 97.1%-103.2%, 95.1%-101.3%, 95.1%
      104.5%, 97.0%-103.5% and 95.9%-104.6%, respectively, and the relative standard
      deviation of all the elements is all below 5.00%.

PMID- 17514980
TI  - [CAIS correction for blood matrix effect on determination of lead concentration
      and isotope ratio by ICP-MS].
AB  - The research studied the influence of matrix effect on the determination of lead
      concentration and isotope ratio through simulating blood matrix, and its
      correction by common analyte internal standardization (CAIS) method. The
      experiment results showed that CAIS method was suitable for the multi-element
      matrix. The relative errors between the determined and the true concentration
      values are 20% (without correction), 8% (by conventional internal reference
      correction) and 2% (by CAIS correction), respectively. Otherwise, the influence
      of matrix effect and its correction for isotope ratio determination are not that
      obvious. Similarity of the mass number and properties between internal reference
      and analyte elements seems not important for CAIS correction, since very close
      correction results were obtained by using Tl and Dy as internal reference
      elements. Besides, correction results are not affected by different matrix
      dilution. Reliability and practicality of CAIS were proved by bovine blood
      standard material determination.

PMID- 17514981
TI  - [Study on elemental speciation analysis and transference characteristics of
      Arnebia euthroma (Royle) Johnst by ICP-MS].
AB  - The elemental transference characteristics and primary speciation analysis of
      Arnebia euthroma (Royle) Johnst were investigated in the present paper. The
      results showed: sealed digestion at high temperature was more efficient and
      thorough than microwave-assisted process (MAP) digestion in the preparation of
      speciation analysis; Most of the elements analyzed, excluding potassium and zinc,
      exist in particulate speciation in the plant; The transference characteristics of
      elements were associated with the polarity of extraction solvents. Contents of
      all 22 elements basically were directly proportional to the polarity of solvents
      varying from almost no polarity to strong, especially for 7 elements: magnesium,
      potassium, calcium, manganese, cobalt, thallium and lead.

PMID- 17514982
TI  - [HG-AFS determination of selenium in Moringa oleifera].
AB  - The Se content in Moringa oleifera was studied by hydride generation atom
      fluorescence spectrometry (HG-AFS) with wet digestion. The effects of the way of
      digestion, the work condition of apparatus, the reaction medium and acidity, and
      the reducing agent and masking agent on the determination of Se were
      investigated. And the operating condition of apparatus was optimized. The results
      showed that the detection limit of Se in this method was 0.42 ng x mL(-1) in the
      linear ranger of 0-120 ng x mL(-1), the relative standard deviation was 3.53% (n
      = 11), and the recovery of the method was 95.2%-104.6%. It was showed that the
      method was very sensitive, simple, rapid and accurate.

PMID- 17514983
TI  - [Application of high performance liquid chromatography and hyphenated techniques
      in analysis of arsenic species].
AB  - Arsenic is a very important nonmetal element in the environment and is vitally
      related to human lives. It is well known that the biological availability and
      toxicological effects of arsenic compounds depend upon their chemical forms, so
      it is necessary to detect the species of arsenic in some environmental samples,
      food, medicine, and body fluids. High performance liquid chromatography (HPLC) is
      widely used in the research on arsenic species because of its high separation
      capability. The detection techniques used for arsenic species analysis have been
      improved rapidly with the gradually increasing demand for sensitivity and
      accuracy. Various hyphenated techniques have also been developed. Inductively
      coupled plasma mass spectrometry has many advantages, such as high sensitivity,
      simultaneous multi-element detection, wide linear range and so on. Therefore,
      high performance liquid chromatography-inductively coupled plasma mass
      spectrometry is widely used in the analysis of arsenic species.

PMID- 17514984
TI  - [Calculation of the contributions of scattering effects to the X-ray fluorescence
      intensities].
AB  - The contribution of scattering effects to the X-ray fluorescence intensity was
      studied for pure element samples, BaB binary samples and fused disk samples by
      theoretic calculation and experiment. Three scattering effects were considered in
      the present study, i. e. coherent scattering effect, incoherent scattering
      effect, and primary fluorescence that was scattered into the direction of
      detector. The study shows that the contribution of scattering effects to the
      intensity of fluorescence is related to the energy of the atomic absorption edge,
      and the sample's matrix. The higher the energy of the atomic absorption edge, the
      more the contribution of scattering effects to the intensity of fluorescence. The
      contribution of scattering effects to the fluorescence intensity is larger for
      light matrix samples than heavy matrix samples. The results of experiment show
      that the accuracy of theoretic calculation was evidently improved when the
      scattering effects were considered in the theoretic calculation for the intensity
      of fluorescence.

PMID- 17514985
TI  - [Application of X-ray photoelectron spectroscopy to the study of complexes and
      its progress].
AB  - X-ray photoelectron spectroscopy (XPS) provides information about the core-level
      binding energies and oxidation states of complexes. It can be used to identify
      the species and valence states of elements, measure the relative content of
      elements, investigate the interaction between ligands and central ions, and
      verify the results obtained by quantum chemistry theory. XPS has been found to be
      a powerful tool for identifying coordination site, evaluating charge
      redistribution, and characterizing geometry of complexes.

PMID- 17514986
TI  - [XPS research on thymine implanted by low energy N+].
AB  - The induced variation mechanism of low energy ion beam implantation into a
      creature has attracted a great attention. DNA was the target of radiation. XPS
      analysis of thymine sample implanted by low energy N+ was studied. It was found
      that the relative content of C, N and O changed in the implanted samples. The
      content of N and O decreased, while that of C increased. Subtle structure of C, N
      and O was studied. It was found that the peak location of O(1s) shifted. The peak
      number of N(1s) changed from one to three, while that of C(1s) changed from two
      to one. The results indicated that the chemical environment and physical
      structure changed greatly by implantation. N+ implantation could lead to
      destruction and change of thymine molecular structure.

PMID- 17514987
TI  - [Method of fused sample preparation after nitrify-determination of primary and
      minor elements in manganese ore by X-ray fluorescence spectrometry].
AB  - Eight components, i. e. Mn, SiO2, Fe, P, Al2O3, CaO, MgO and S, in manganese ore
      were determined by X-ray fluorescence spectrometer. Because manganese ore sample
      releases a lot of air bubbles during fusion which effect accuracy and
      reproducibility of determination, nitric acid was added to the sample to destroy
      organic matter before fusion by the mixture flux at 1000 degrees C. This method
      solved the problem that the flux splashed during fusion because organic matter
      volatilized brought out a lot of air bubbles, eliminated particle size effects
      and mineral effect, while solved the problem of volatilization of sulfur during
      fusion. The experiments for the selection of the sample preparation conditions,
      i. e. fusion flux, fusion time and volume of HNO3, were carried out. The matrix
      effects on absorption and enhancement were corrected by variable theoretical
      alpha coefficient to expand the range of determination. Moreover, the precision
      and accuracy experiments were performed. In comparison with chemical analysis
      method, the quantitative analytical results for each component are satisfactory.
      The method has proven rapid, precise and simple.

PMID- 17514988
TI  - [Spectra study on the influence of drying process on palygorskite structure].
AB  - There are four different types of molecules of hydroxyl groups of the natural
      attapulgite. The band at 3614 cm(-1) was attributed to the stretching modes of
      hydroxyls coordinated with the magnesium. The band at 3415 cm(-1) is associated
      with the hydroxyl stretching vibrations of absorbed water. The bands at 3581 and
      3552 cm(-1) were attributed to the symmetric and antisymmetric stretching modes
      of molecular water coordinated with the magnesium at the edges of the channels.
      The band at 1653 cm(-1) is associated with the hydroxyl stretching vibrations of
      zeolitic water. The structures of the natural palygorskite and its products dried
      at different temperatures for 30 min were analysed by Fourier transform infrared
      spectroscopy (FTIR) and X-ray diffraction (XRD). The absorbed, zeolitic and co
      ordinated water decreased during the drying process at the same time. The
      absorbed water was completely-dehydrated firstly, then the zeolitic water, and
      lastly the co-ordinated water. And the hydroxyl groups remained until about 600
      degrees C. When the co-ordinated water was dehydrated completely at 450 degrees
      C, the crystalloid was destroyed. The mechanism of the palygorskite structure
      change was also discussed in detail.

PMID- 17514989
TI  - [Influence of spectrometer scanning requirements in homemade grating diffuse NIR
      instrument on NIR veracity].
AB  - The influence of instrument parameters, such as scan internal, length of
      instrument run, frequency of scan background etc, on NIR veracity was studied
      with a homemade grating diffuse NIR instrument using Yunnan flue-cured tobacco.
      Results showed that scan interval, such as 8 nm or 16 nm, had no evident
      influence on NIR quantitative analysis. To improve scan speed, the scan interval
      the authors decided to use was 16 nm. NIR model was set up which could revise the
      influence of the length of instrument run. This instrument can clue on baseline
      shift to decide the frequency of background scanning, which can deduce NIR
      analysis error and improve NIR veracity.

PMID- 17514990
TI  - Seeing the unseen.

PMID- 17514991
TI  - How interdisciplinary documentation improves the bottom line.

PMID- 17514992
TI  - The voices of rehabilitation nursing.

PMID- 17514993
TI  - Hope for love: practical advice for intimacy and sex after stroke.
AB  - Stroke survivors are a major group of patients served by rehabilitation nurses.
      The lingering sequelae of a stroke may be devastating to a couple's relationship.
      This article provides practical advice that nurses can give to a stroke patient
      and his or her partner to cope with or overcome changes in intimacy and sexuality
      after a stroke. This article addresses the wide range of changes likely to occur
      in the patient and his or her partner, and readers are referred to additional
      resources for the nurse, the patient, and his or her partner. This information
      provides the tools for nurses to help our patients and their partners maintain
      their hope for love.

PMID- 17514994
TI  - Exercise adherence in patients with chronic obstructive pulmonary disease: an
      exploration of motivation and goals.
AB  - Adherence to an exercise regimen is challenging. Motivation is an important
      factor that can enhance exercise adherence. A key component of motivation is the
      setting and accomplishment of specified goals. Therefore, it is important to
      understand the relationship between patients' motivation and goals. Motivation
      and goal orientation in 14 participants with chronic obstructive pulmonary
      disease were assessed. Participants were also interviewed to explore their
      exercise and activity goals. Motivation was significantly associated with goal
      orientation. In addition, participants reported many explicit activity goals, but
      few participants had set specific exercise goals. The inconsistency between
      activity and exercise goals has not been reported previously. Findings from this
      preliminary study provide novel and relevant information that may help care
      providers understand factors that may influence exercise adherence in people with
      chronic obstructive pulmonary disease.

PMID- 17514995
TI  - The experience of adolescent women living with spina bifida. Part II: Peer
      relationships.
AB  - Relationships are much more complex for those with disabilities than for those
      without disabilities. This study was part of a larger mixed-method investigation
      that explored comprehensive aspects of adaptation in adolescents with spina
      bifida (SB). The purpose of this qualitative component of the study was to
      explore the experiences of peer relationships in 31 adolescent women with SB. The
      participants were interviewed, and analysis was conducted for common themes. The
      five major themes and one subtheme were peers without disabilities (subtheme:
      peers with disabilities), normalization, challenges in peer connectedness, peer
      connectedness with adults, and romantic connectedness. Whereas some participants
      voiced close connections with peers, others described prejudices, stereotyping,
      and limited dating experiences. Results from this study support the need for
      comprehensive assessment of social relationships in adolescent women with SB and
      active interventions to address problems identified. Rehabilitation nurses are in
      a key position to implement social interventions in adolescents and young women
      with SB.

PMID- 17514996
TI  - Strategies to reduce risk of fall-related injuries in rehabilitation nursing.
AB  - Rehabilitation nurses are in a critical position to lead interdisciplinary team
      fall prevention management, including injury risk reduction. This article
      provides an update for rehabilitation nurses on evidence-based strategies to
      reduce patients'risk of fall-related injuries. This content builds on existing
      literature by focusing on knowledge to promote patient responses that reduce the
      risk of falls and ultimately fall-related injuries. Although rehabilitation
      nurses understand the complex nature of falls, addressing the intrinsic and
      extrinsic risk factors that increase the risk of fall-related injuries requires
      both individually based treatment programs and a system-wide commitment. A
      plethora of literature discusses fall risks and falls, but this article profiles
      the at-risk patient and describes current and emerging evidence-based
      interventions to protect patients from fall-related injuries by reducing risk
      factors. This discussion is limited to exercise, environmental redesign,
      osteoporosis prevention, and hip protectors.

PMID- 17514997
TI  - The acute care for elders unit: taking the rehabilitation model into the hospital
      setting.
AB  - Older Americans are living longer than ever before. Those over the age of 65
      years account for almost 13% of the population and one third of all
      hospitalizations. Older adults are much more likely than younger adults to
      develop complications during hospitalization. With the increasing number of older
      adults at higher risk of hospitalization, it is more important than ever to study
      and develop ways to minimize the cascade of dependency that can occur during
      hospitalization. The Acute Care for Elders unit model has been shown to improve
      the processes of hospital care, discharge outcomes, and the prevention of
      functional limitations for the acutely ill older adult.

PMID- 17514998
TI  - Operational mental health: a user's guide for medical staff.

PMID- 17514999
TI  - Mental health referrals to the Falkland Islands British Military Mental Health
      Team, 1986-96.
AB  - OBJECTIVES: To examine the pattern of out-patient mental health care referrals
      for military personnel deployed to the Falklands Islands, 1986-96. METHODS: Data
      from referral books of British Military Community Mental Health Nurses based in
      the Falkland Islands were abstracted, entered into an electronic database and
      analysed. RESULTS: Over the period 1986-96, 538 Service personnel were referred
      to the mental health out-patient facility on the Falkland Islands. The majority
      were male (96%) and junior ranks (81%). Approximately a third of patients were
      referred for reasons relating to alcohol (31%) and for over two-thirds of
      patients no follow-up was required (68%). Differences were observed by Service
      with the Army having more referrals due to alcohol than the other two Services,
      whilst the Navy had more deliberate self-harm referrals and the RAF more
      referrals for anxiety. CONCLUSIONS: The lack of information on the total
      population deployed to the Falkland Islands over this period limits the
      interpretation of the results.

PMID- 17515000
TI  - VELA deployment 2006.

PMID- 17515001
TI  - Re-VELA-tion--a report on the role 2 / medical augmentee deployment to OP VELA.

PMID- 17515002
TI  - William Balfour Baikie and the prevention of malaria.

PMID- 17515003
TI  - Legislation to solidify the foundation of health promotion: Health Promotion
      FIRST.

PMID- 17515004
TI  - Availability of lactation counseling services influences breastfeeding among
      infants admitted to to neonatal intensive care units.
AB  - PURPOSE: To assess the association between the presence of international board
      certified lactation consultant (IBCLC) services at a delivery hospital and the
      breastfeeding practices of women whose infants required neonatal intensive care
      unit (NICU) admission. DESIGN: Cross-sectional study using population-level data.
      SETTING: Philadelphia, Pennsylvania. SUBJECTS: 2132 infants admitted to the NICU.
      MEASURES: Breastfeeding at hospital discharge was measured with the question, "Is
      the infant being breastfed?" Delivery hospitals were dichotomized as to the
      presence or absence of an IBCLC on staff ANALYSIS: Logistic regression was used
      to assess the relationship between breastfeeding at discharge and the presence of
      an IBCLC at the delivery facility while adjusting for maternal characteristics
      and birth outcomes. RESULTS: Among mothers of infants admitted to the NICU,
      breastfeeding rates among mothers who delivered at hospitals with an IBCLC were
      nearly 50% compared with 36.9% among mothers who delivered at hospitals without
      an IBCLC. The adjusted odds of breastfeeding initiation prior to hospital
      discharge were 1.34 (95% confidence interval = 1.03, 1.76) times higher for women
      who delivered at a facility with an IBCLC. CONCLUSIONS: To increase breastfeeding
      rates among the NICU population, these findings support the need for universal
      availability of IBCLCs at delivery facilities that have NICUs.

PMID- 17515005
TI  - Smoking policies in small worksites in Minnesota.
AB  - PURPOSE: To examine correlates of smoking policies in a stratified sample of
      small worksites in Minnesota and to determine knowledge and attitudes of the
      owners and managers regarding the Minnesota Clean Indoor Air Act (MCIAA) rules
      that newly applied to their businesses. DESIGN: Cross-sectional survey. SETTING:
      Minnesota offices and factories/warehouses with 5 to 50 employees. Subjects.
      Owners or managers of offices and factories/warehouses; sample size = 233;
      response rate = 66%. MEASURES: Existence and strength of worksite smoking
      policies. ANALYSIS: Comparison of factories/warehouses and offices in
      metropolitan and greater Minnesota using chi square and linear and logistic
      regression analyses. RESULTS: Approximately two-thirds of the worksites claimed
      to have a smoking policy, but only 26% of the total sample had a policy in
      writing. Worksites that offered health insurance to their employees were more
      likely to have a written policy (p < .0001), as were offices in the metro area
      compared with other worksites (p = .003). Policies of both types of outstate
      worksites were stronger compared with those at metro sites, and offices had
      stronger policies than factories and warehouses in the metro area. Only about one
      third of the businesses had heard of the MCIAA rule changes. CONCLUSION: Most
      small businesses in Minnesota do not have a smoking policy in writing and thus
      their employees are at risk of exposure to secondhand smoke at work.

PMID- 17515006
TI  - Use of Medicare summary notice inserts to generate interest in the Medicare stop
      smoking program.
AB  - PURPOSE: Evaluations of outreach strategies that effectively and efficiently
      reach the senior population often go unreported. The Medicare Stop Smoking
      Program (MSSP) was a seven-state demonstration project funded by the Centers for
      Medicare and Medicaid Services. The 1-year recruitment plan for MSSP included a
      multifaceted paid media campaign; however, enrollment was slower than
      anticipated. The purpose of this substudy was to test the effects of including
      envelope-sized advertisement inserts with Medicare Summary Notices (MSNs) as a
      supplemental recruitment strategy. METHODS: Information obtained from enrollees
      on where they had learned about the program as well as overall enrollment rates
      were analyzed and compared with the time periods during which the inserts were
      included in MSN mailings. RESULTS: Average call volume to the enrollment center
      increased by 65.7% in Alabama, the pilot state, and by more than 200% in the
      subsequent demonstration states. Despite the introduction of the MSN inserts late
      in the recruitment period, 32.2 % of the 7354 total enrollees stated that they
      learned about the project through the inserts. CONCLUSIONS: This recruitment
      method is highly recommended as a cost-effective way to reach the senior
      population.

PMID- 17515007
TI  - The use of the processes of change across the exercise stages of change and
      across varying intensities and frequencies of exercise behavior.
AB  - PURPOSE: Determine the use of the processes of change (POC) across the exercise
      stages of change and across varying intensities and frequencies of exercise
      behavior. DESIGN: Cross-sectional design. SETTING: University setting. SUBJECTS:
      Questionnaires were collected from 699 college-aged individuals. MEASURES: Data
      were collected for exercise stages of change, POC and exercise behavior. Self
      report exercise data were categorized as 0 days, 1 to 2 days, and 3 or more days
      per week of moderate and vigorous exercise. ANALYSIS: MANOVA assessed differences
      in the use of the 10 POC across the stages of change and across varying
      frequencies of moderate and vigorous exercise behavior. RESULTS: Results showed
      all 10 POC were significant between the exercise stages of change and differing
      frequencies of moderate and vigorous exercise behavior. Post hoc analysis
      identified 7 significant processes between adjacent exercise stages of change, 10
      significant processes between differing frequencies of moderate exercise
      behavior, and 9 significant processes between differing frequencies of vigorous
      exercise behavior. CONCLUSIONS: The results for this study suggest that intensity
      and frequency may be factors in the use of the POC. The use of the POC showed a
      linear increase across stage, which deviates from the proposed Transtheoretical
      Model framework and previous research. Additional investigation into the
      processes and stages of change, and their role in changing exercise behavior is
      needed.

PMID- 17515008
TI  - Realistic expectations: investing in organizational capacity building for chronic
      disease prevention.
AB  - PURPOSE: This article presents findings that explore investment in organizational
      capacity building for chronic disease prevention. Specifically, this analysis
      examines variation in investment inputs, intervention outputs, and capacity
      changes to inform expectations of health-promotion capacity-building investment.
      DESIGN/SETTING: This multiple case study involving both qualitative and
      quantitative data is based on seven provincial dissemination projects involved in
      the Canadian Heart Health Initiative. METHODS: Data on investment, number, and
      type of capacity-building activities and capacity changes come from a
      questionnaire, key informant interviews, and project report analysis.
      Quantitative data were analyzed descriptively and for trends, while qualitative
      data were analyzed thematically. RESULTS: Per capita investments in capacity
      building ranged from a low of $0.21 in Ontario to $167.41 in Prince Edward
      Island. Multiple, tailored capacity-building interventions were used in each
      project. Mostly positive but modest changes were observed in at least five
      dimensions of capacity in all but one project. CONCLUSION: These findings reveal
      that capacity building for chronic disease prevention requires a long-term
      investment and is context specific. Even limited investment can produce
      interventions that appear to positively influence capacity for chronic disease
      prevention. The findings also suggest an urgent need to expand surveillance to
      include indicators of capacity-building investments and interventions to allow
      policy makers to make more informed decisions about investments in public health.

PMID- 17515009
TI  - Selected barriers and incentives for worksite health promotion services and
      policies.
AB  - PURPOSE: To assess employees'attitudes toward potential barriers to and
      incentives for their likely use of worksite health promotion services. METHODS:
      Data from the 2004 HealthStyles Survey, a volunteer mail survey, were used to
      examine selected barriers to, incentives for, and potential use of worksite
      health promotion programs among adults employed full-time or part-time outside
      the home (n = 2337). RESULTS: Respondents were 72.7% white and 52.1 % female;
      36.5 % were college graduates, 30.7% had a body mass index of at least 30, and
      35.6% were regularly active. The most common reported barriers to use of worksite
      services were no time during the workday (42.5 %) and no time before or after
      work (39.4%). More than 70% of employees responded that the following incentives
      would promote their interest in participating in a free worksite wellness
      program: convenient time, convenient location, and employer-provided paid time
      off during the workday. Preferred health promotion services reported by
      respondents were fitness centers (80.6%), weight loss programs (67.1 %), and on
      site exercise classes (55.2 %). Policy practices of paid time to exercise at work
      and healthy vending or cafeteria food choices were preferred by almost 80% of
      employees. CONCLUSIONS: These HealthStyles Survey data, in combination with needs
      data from an employer's own workforce, may help employers design wellness
      programs to include features that attract employees.

PMID- 17515010
TI  - Attributes of environments supporting walking.
AB  - PURPOSE: This study established a framework to audit environments supporting
      walking in neighborhoods. DESIGN: Cross-sectional analysis using a telephone
      survey and 200 objective environmental variables. SETTING. Urbanized King County,
      WA. SUBJECTS. 608 randomly sampled adults. Measures. Walking measures constructed
      from survey questions; objective environmental measures taken from parcel-level
      databases in Geographic Information Systems. ANALYSIS: Multinomial models
      estimated the odds of people engaging in moderate walking (<149 min/wk) and in
      walking sufficiently to meet recommendations for health (150+ min/ wk), relative
      to not walking" and in walking sufficiently, relative to walking moderately. A
      base model consisted of survey variables, and final models incorporated both
      survey and environmental variables. RESULTS. Survey variables strongly associated
      with walking sufficiently to enhance health included household income, not having
      difficulty walking, using transit, perceiving social support for walking walking
      outside of the neighborhood, and having a dog (p < .01). The models isolated 14
      environmental variables associated with walking sufficiently (pseudo R2 up to 0.
      46). Measures of distance to neighborhood destinations dominated the results:
      shorter distances to grocery stores/markets, restaurants, and retail stores, but
      longer distances to offices or mixed-use buildings (p < .01 or .05). The density
      of the respondent's parcel was also strongly associated with walking sufficiently
      (p < .01). Conclusions. The study offered valid environmental measures of
      neighborhood walkability.

PMID- 17515011
TI  - The relationship between obesity and injuries among U.S. adults.
AB  - PURPOSE: To quantify the relationship between body mass index (BMI) and rates of
      medically attended injuries by mechanism (overall, fall, motor vehicle, and sport
      related) and by nature (strain/sprain, lower extremity fracture, and
      dislocations), and between BMI and injury treatment costs. DESIGN: Cross
      sectional analysis. SETTING. The noninstitutionalized population of the United
      States. SUBJECTS: The 1999-2000, 2000-2001, and 2001-2002 waves of the Medical
      Expenditure Panel Survey, a large, nationally representative dataset, were
      combined to create the analysis sample. The final sample included 42,304 adults.
      MEASURES. Medically attended injury rates by mechanism and nature of injury and
      related treatment costs. ANALYSIS: Logistic regressions were used to separately
      estimate the odds of sustaining any injury by mechanism or by nature for
      overweight (25 < BMI : 29.9) and three categories of obese individuals compared
      with those who were normal weight. A second set of regressions tested whether,
      given that an injury occurred, obese individuals had greater injury treatment
      costs. RESULTS. Slightly more than one in five adults sustain an injury each year
      that requires medical treatment. The odds of sustaining an injury are 15%
      (overweight) to 48% (Class III obesity) greater among those with excess weight.
      Conditional on sustaining an injury, BMI did not have a significant impact on
      injury treatment costs. CONCLUSION: Our findings show a clear association between
      BMI and the probability of sustaining an injury. If increasing BMI is causing the
      rise in injury rates, then the incidence of injuries, including those related to
      falls, sprains/strains, lower extremity fractures, and joint dislocations, are
      likely to increase as the prevalence of obesity increases.

PMID- 17515012
TI  - Regulatory and tax issues for worksite wellness programs.
AB  - Worksite wellness programs continue to grow and find expression in employer
      organizations of all types. As these programs mature and are offered to larger
      and larger numbers of employees in more worksites increased opportunity exists
      for regulatory problems. Applicable legislation and major federal regulatory
      issues affecting worksite wellness programs are explored and categorized. Final
      rules regarding Title I non-discrimination provisions of the Health Insurance
      Portability and Accountability Act of 1996 (HIPAA) are described and implications
      for employers are identified. Due to the increasing importance of incentive
      rewards in programming, the tax implications of various types of program
      expenditures are also described. Finally, suggestions for legislative amendments
      and regulatory changes that would enhance wellness program effects are described.

PMID- 17515014
TI  - New study shines light on poor transfer communications.
AB  - Direct communication between hospital physicians and primary care physicians
      occurs infrequently. The Joint Commission's deadline for transmission of
      discharge forms may be too generous. Discharge forms should be disseminated
      within one week, and they should be complete.

PMID- 17515015
TI  - Joint Commission report shows quality gains.
AB  - Greatest improvement occurred in providing smoking cessation advice to patients
      admitted to the hospital with pneumonia. Pneumococcol vaccinations, discharge
      instructions for heart failure patients need improvement. Low compliance with
      timeout standards remains a nagging problem.

PMID- 17515016
TI  - Interventions improve care, not necessarily outcomes.
AB  - Treatment of asthma, diabetes patients shows significant process improvements.
      Limited access to meds for the uninsured helps explain some of the disappointing
      results. Mutually agreed-upon treatment plans an important component of the Care
      Model.

PMID- 17515017
TI  - IPRO, New York Q10, wins prestigious quality award.
AB  - Registration to the ISO-9001 Quality System Standard helps QIO stand out. IPRO
      leaders say they have to walk the 'quality walk' if they are to serve hospitals.
      Organization stresses effective employee communications, training, and rewards
      and recognition.

PMID- 17515018
TI  - Collaborative aimed at hospital communication.
AB  - All of the hospitals in Kentucky will participate in, benefit from the
      collaborative. Having a program in place for improved communications a major step
      in providing quality care to targeted populations. Pilot program will use symbols
      to communicate information about injuries, patients' needs.

PMID- 17515019
TI  - The life cycles of women: restoring balance.

PMID- 17515020
TI  - Infection, depression, and immunity in women after coronary artery bypass: a
      pilot study of cognitive behavioral therapy.
AB  - CONTEXT: Depression is common after coronary artery bypass graft (CABG) surgery,
      but little is known about its effect on post-CABG inflammation or infection or
      about the most effective treatment for post-CABG depression. OBJECTIVES: (1) To
      determine ifpost-CABG depression is associated with increased infectious illness
      and (2) to test effects of cognitive behavioral therapy (CBT) on depressive
      symptoms, inflammatory biomarkers, and post-CABG infections in depressed post
      CABG women. DESIGN: Randomized, controlled trial. SETTING: Two urban tertiary
      care centers. PATIENTS: Fifteen clinically depressed women in the first month
      after CABG, along with a comparison group of 37 non-depressed postCABG women,
      were studied. Inclusion criteria were: < or = 75 years old, English-speaking,
      undergoing first-time CABG, available for 6 months offollow-up, and without
      malignancy or autoimmune disorders. INTERVENTION: Eight weeks of individual home
      based CBT. MAIN OUTCOME MEASURES: (1) Depressive symptoms measured by the Beck
      Depression Inventory, (2) natural killer cell cytotoxicity (NKCC) measured by
      51Cr-release assay, (3) infectious illness episodes measured by the Modified
      Health Review, (4) interleukin (IL)-6 and C reactive protein (CRP) measured by
      enzyme immunoabsorbent assay. RESULTS: Clinically depressed post-CABG women
      exhibited decreased NKCC and a higher incidence of in-hospital fevers and
      infectious illness in the first 6 months after CABG. Among depressed women, CBT
      yielded moderate to large effects for improved NKCC (D=0.67) and decreased IL-6
      (D=0.61), CRP (D=0.85), and postoperative infectious illnesses (D=0.93). CBT
      holds promise for improving depression and immunity and reducing infection and
      inflammation after CABG.

PMID- 17515021
TI  - Menopausal issues: a national probability sample of US women.
AB  - OBJECTIVE: This survey assessed women's reported information sources about
      menopause, interactions with physicians concerning use of and compliance
      concerning conventional and alternative therapies for symptoms, and factors
      determining choices of symptom support. DESIGN: The study was a nationwide
      probability survey of menopausal women regarding their symptoms, their attitudes
      toward menopause and concerns about the menopause experience, what they use as
      sources of information about menopause, their evaluation of healthcare
      professionals' competence in addressing patients' concerns, self-evaluation of
      communication with a healthcare professional about concerns, their feelings about
      herbal remedies and other complementary and alternative medicine treatment
      options, and what they consider the most important factor(s) in choosing a
      treatment option for menopause. RESULTS: Physicians were the most common source
      of menopause information. Physician opinions are more frequently sought than
      other sources. About 40% of respondents are comfortable with using over-the
      counter or herbal remedies for menopausal symptoms. Only 19% had discussed use of
      herbal supplements with their physicians. CONCLUSION: This study unveiled women's
      opinions about treatment options for menopause. More in-depth studies regarding
      efficacy and/or side effects of each available treatment are the relevant next
      step, given the prevalence of both hormone replacement therapy and alternative
      therapies and the controversies surrounding them.

PMID- 17515022
TI  - Reduction of fibromyalgia symptoms through intravenous nutrient therapy: results
      of a pilot clinical trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a modified Myers' formula of
      intravenous nutrient therapy (IVNT) on the symptoms of fibromyalgia (FM) in
      therapy-resistant FM patients. METHODS: In this pilot clinical trial, 7
      participants with therapy resistant FM were given IVNT once per week for 8 weeks.
      Patient's pain levels, fatigue, and activities of daily living were evaluated
      weekly. RESULTS: All participants reported decreased pain levels, decreased
      fatigue, and increased activities of daily living. Participants noted increased
      energy levels within 24-48 hours of the initial infusion. At the end of the
      study, all participants reported increased energy and activities of daily living
      as well as a 60% reduction in pain (P=.005) and an 80% decrease in fatigue (P=
      .005). No participants, however, reported complete or lasting resolution of pain
      or fatigue. No side effects were reported. DISCUSSION: Anecdotal reports have
      indicated benefit for IVNT for patients with chronic pain, including FM. However,
      except for 2 reports, the medical literature is devoid of any studies of IVNT for
      the treatment of FM. In this pilot study, 7 participants received IVNT once a
      week for 8 weeks. All participants had long-standing FM (at least 8 years) and
      had tried conventional therapies, such as antidepressants, nonsteroidal anti
      inflammatory drugs, and exercise, without significant or lasting relief. All had
      improvement in symptoms and increases in their activities of daily living,
      although no participant reported complete resolution of symptoms. IVNT appears to
      be safe to reduce FM symptoms.

PMID- 17515023
TI  - In vitro fertilization and acupuncture: clinical efficacy and mechanistic basis.
AB  - OBJECTIVE: To provide an overview of the use of acupuncture as an adjunct therapy
      for in vitro fertilization (IVF), including an evidence-based evaluation of its
      efficacy and safety and an examination of possible mechanisms of action. DESIGN:
      Literature review using PubMed, the Science Citation Index, The Cochrane Library
      (Database of Systematic Reviews and Central Register of Controlled Trials), the
      New England School of Acupuncture library databases, and a cross-referencing of
      published data, personal libraries, and Chinese medicine textbooks. RESULTS:
      Limited but supportive evidence from clinical trials and case series suggests
      that acupuncture may improve the success rate of IVF and the quality of life of
      patients undergoing IVF and that it is a safe adjunct therapy. However, this
      conclusion should be interpreted with caution because most studies reviewed had
      design limitations, and the acupuncture interventions employed often were not
      consistent with traditional Chinese medical principles. The reviewed literature
      suggests 4 possible mechanisms by which acupuncture could improve the outcome of
      IVF: modulating neuroendocrinological factors; increasing blood flow to the
      uterus and ovaries; modulating cytokines; and reducing stress, anxiety, and
      depression. CONCLUSIONS: More high-quality randomized, controlled trials
      incorporating placebo acupuncture controls, authentic acupuncture interventions,
      and a range of outcome measures representative of both clinical outcomes and
      putative mechanistic processes are required to better assess the efficacy of
      acupuncture as an adjunct for IVF.

PMID- 17515024
TI  - Solving the puzzle of hormone replacement.

PMID- 17515025
TI  - Why we need holism in pregnancy care: a review.

PMID- 17515026
TI  - Christiane Northrup, MD: a pioneer in the field of women's health.

PMID- 17515027
TI  - Effect of beta-casomorphines on mother-oriented ("child's") behavior of white
      rats.

PMID- 17515028
TI  - Discrimination of the spectral structure of sound signals under the conditions of
      dichotic release from interfering noise.

PMID- 17515029
TI  - Myelopeptides in treatment for stress- and injury-induced changes in the immune
      response to a heterologous thymus-dependent antigen in rats with penetrating eye
      wounds.

PMID- 17515030
TI  - The possible involvement of calcium ions in the regulatory effect of oxidized
      glutathione on macrophages.

PMID- 17515031
TI  - Expression of atrial depolarization on the body surface.

PMID- 17515032
TI  - Schizophrenia and autoantibodies against the regulatory peptide 5HT-modulin.

PMID- 17515033
TI  - Exploratory behavior and anxiety level of white outbred rats after blocking
      olfaction with N-trimethylindole (skatole).

PMID- 17515034
TI  - Increased number of B chromosomes in the eastern Asian mice Apodemus peninsulae
      (Rodentia, Muridae) from a mountain Altai population.

PMID- 17515035
TI  - The reproductive strategy and immune status of rodents in an environment altered
      by industrial activity.

PMID- 17515036
TI  - The population of the barnacle Semibalanus balanoides in the salinity gradient of
      the estuarial zone of the Kola Bay Cove.

PMID- 17515037
TI  - Comparative phosphatase histochemistry in skin glands of laboratory and wild
      Norway rats (Rattus norvegicus).

PMID- 17515038
TI  - On Fisher's fundamental theorem of natural selection for space-structured
      populations under the conditions of strong migration.

PMID- 17515039
TI  - Variability of the chromosome 1 HSR of "Asian" type in the wild mouse (Mus
      musculus).

PMID- 17515040
TI  - Craniometric identification of three closely related forms of the common vole
      microtus arvalis sensu lato.

PMID- 17515041
TI  - Spatial ethological structure and evolution of sociality in rodents.

PMID- 17515042
TI  - Effect of harvesting on the genetic diversity and dynamics of a Mendelian limited
      population.

PMID- 17515043
TI  - Sexual maturation of daughters depends on the mother's body condition during
      pregnancy: an example of the water vole Arvicola terrestris L.

PMID- 17515044
TI  - The LEPIDIUM-LIKE gene determines stem cell activity during formation of petals
      and stamens in Arabidopsis thaliana flowers.

PMID- 17515045
TI  - Changes in juvenile hormone hydrolysis rate and dopamine level in the hemolymph
      of Galleria mellonella L. (Lepidoptera, Pyralidae) during mycosis.

PMID- 17515046
TI  - Relationship of the chlorophyll content with the biomass and disperse structure
      of phytoplankton.

PMID- 17515047
TI  - Lithium-concentrating plant species and their pharmaceutical usage.

PMID- 17515048
TI  - Titers of the molting hormones in king crabs from the Barents Sea.

PMID- 17515049
TI  - Melanocytes of the limbus vascular network are involved in the regeneration of
      the eye cornea of adult newts Pleurodeles waltl.

PMID- 17515050
TI  - Role of diapause in coexistence of zooplankton species: model analysis.

PMID- 17515051
TI  - Pollen heteromorphism in Panax ginseng C.A. Meyer (Araliaceae) anthers.

PMID- 17515052
TI  - Effect of free calcium ions on the proliferative activity and viability of mouse
      embryonic stem cells.

PMID- 17515053
TI  - Detection of herpes simplex virus genomic DNA in spermatozoa of patients with
      fertility disorders by in situ hybridization.

PMID- 17515054
TI  - Effect of low-intensity laser irradiation on the chemical composition and
      structure of lipids in wheat tissue culture.

PMID- 17515055
TI  - Ultrastructural changes in the Aerbach plexus of the suckling rabbit small
      intestine in experimental cholera.

PMID- 17515056
TI  - Trimetazidine decreases Ca2+ response to thapsigargin in differentiated and
      undifferentiated human HL-60 cells.

PMID- 17515057
TI  - [Aleksandr Alekseevich Shalimov--surgeon, scientist, prominent figure].

PMID- 17515058
TI  - [Aleksandr Alekseevich Shalimov in Khar'kov. First "Shalimov" Institute].

PMID- 17515059
TI  - [Shalimov's foundations of the treatment of the esophagus and stomach cancer with
      invasion to the esophagus].

PMID- 17515060
TI  - [The role of the academician A.A. Shalimov in development of the stomach
      surgery].

PMID- 17515061
TI  - [Scientific and practical legacy of the academician A.A. Shalimov in the modern
      liver surgery].

PMID- 17515062
TI  - [Surgical treatment of the postcholecystectomy bile duct strictures and
      injuries].

PMID- 17515063
TI  - [A.A. Shalimov and modern approaches to the surgical treatment of cancer of the
      pancreatic head and periampullar zone organs].

PMID- 17515064
TI  - [A.A.Shalimov's scientific school and microsurgery in Ukraine].

PMID- 17515065
TI  - [Thirty five year experience in experimental surgery in the Institute of Surgery
      and Transplantology].

PMID- 17515066
TI  - [Surgical treatment of severe postoperative peritonitis].

PMID- 17515067
TI  - [Alternative bypass grafting methods in arterial occlusion of the femoro
      popliteal-tibial segment].

PMID- 17515068
TI  - Conservative management of small renal tumors.
AB  - With the widespread use of imaging modalities, incidentally discovered small
      renal cell carcinomas have increased. Some patients, however, are too old or weak
      due to various diseases to undergo surgery and other patients occasionally refuse
      surgery. To investigate the natural history of small renal cell carcinoma, we
      retrospectively reviewed patients with small renal tumors suggestive of
      carcinoma. We retrospectively reviewed 15 patients with contrast-enhancing renal
      masses less than 4.0 cm in diameter who were observed without treatment. The mean
      follow-up period was 38 months (range, 8-91). The average patient age was 67
      years (range, 44-87). The initial average tumor diameter was 2.2 cm (range, 1.0
      3.9). The average growth rate was 0.06 cm per year (range, -0.09-0.28). Only 4
      tumors grew obviously during the follow-up period. Three tumors were removed
      surgically by radical nephrectomy, and all tumors were pathologically diagnosed
      as renal cell carcinoma. None of the patients developed metastases during the
      follow-up period or after surgery. Two patients died of other causes. Nonsurgical
      watchful waiting may be an acceptable treatment option for elderly or severely
      comorbid patients; however, it is not known whether this conservative management
      can be applied to young or otherwise healthy patients.

PMID- 17515069
TI  - Adverse events of MVAC chemotherapy in patients with advanced urothelial cancer
      of the bladder.
AB  - There have only been a few reports about adverse events of methotrexate,
      vinblastine, adriamycin and cisplatin (MVAC) chemotherapy under supportive care
      with granulocyte stimulating factor (G-CSF) and 5-hydroxytryptamine 3 receptor (5
      HT3R) antagonists. The purpose of this study was to retrospectively review the
      adverse events of the chemotherapy. We analyzed 59 patients with advanced bladder
      cancer who received MVAC chemotherapy at Sapporo Medical University hospital from
      January 1992 to September 2004. The adverse events were evaluated according to
      the Common Terminology Criteria for Adverse Events version 3.0 (Japanese
      edition). Thirty-one of the 59 patients (52.6%) received MVAC in the neoadjuvant
      setting. Two courses of chemotherapy were most frequently used in the neoadjuvant
      and adjuvant settings, and treatment of metastatic or recurrent lesions. More
      than 90% of patients experienced hematological adverse events such as some grade
      of leukocytopenia and neutropenia in each course of the chemotherapy. Grade 3 or
      4 neutropenia was seen in 60-75% of patients. Grade 3 or 4 leukopenia and/or
      neutropenia in the first course of the chemotherapy was associated with patients
      with impaired renal function (60 mL/min< or = creatinine clearance <80 mL/min).
      Febrile neutropenia was found in 6 patients (5.0%), including one who died of
      subsequent septic shock and adult respiratory distress syndrome. Nausea was seen
      in 70-80% of patients. MVAC chemotherapy for advanced bladder cancer was
      performed with tolerable adverse events. The current results provide relevant
      information mainly for those who need 2 courses of chemotherapy in the
      neoadjuvant or adjuvant setting.

PMID- 17515070
TI  - [Investigation of resection and coagulation times during transurethral resection
      of the prostate among operators determined using a time-measuring instrument].
AB  - We investigated resection and coagulation times for 123 patients with lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia who underwent
      transurethral resection of the prostate (TUR-P) and their differences among
      surgeons. The numbers of cases of TUR-P in this study were 57 for Doctor A
      (experienced about 4000 cases), 60 for Doctor B (experienced about 100 cases) and
      6 for a visiting physician (experienced about 50 cases). We measured resection
      and coagulation times by turning on a time-measuring instrument that was made
      using commercially available parts. There were significant differences in entire
      operation time, and operation, resection and coagulation times per resected
      weight of the tissue among the 3 doctors (Doctor A < Doctor B < visiting
      physician, p < 0.0001, Kruskal-Wallis test). The percentage of total operation
      time accounted for by resection time and coagulation time in TUR-P was 37% for
      doctor A, whereas it was 27% for doctor B and that for the visiting physician was
      21% (p < 0.0001, Kruskal-Wallis test). Thus, for doctors with more experience
      resection time and coagulation time accounted for higher percentages of total
      operation time. The measuring instrument is inexpensive and has the potential to
      be a useful tool for checking a surgeon's skill.

PMID- 17515071
TI  - [Two cases of hyperthyroidism induced by interferon-alpha therapy for renal cell
      carcinoma].
AB  - Autoimmune thyroid disease is the result of a common side-effect of interferon
      alpha (IFN-alpha) used to treat viral hepatitis C; but there have been few
      reports on thyroid disorders induced by IFN-a that was used to treat renal cell
      carcinoma. IFN-alpha therapy was conducted on two male patients, 75 and 44 years
      old, after radical nephrectomy. Six and five months, respectively, after this
      therapy, they complained of weight loss. Laboratory evaluation revealed
      hyperthyroidism; the thyroid stimulating hormone (TSH) level fell below normal;
      and the serum free T3 and T4 levels increased above normal values. Two months
      after the termination of IFN-alpha therapy, their thyroid hormone levels returned
      to normal without the help of antithyroid agents. In observational studies,
      thyroid dysfunction has been reported in 0.6 to 30% of the patients who had been
      treated with IFN-alpha. Careful observation is necessary to watch for the
      possible development of thyroid disorder during IFN-alpha therapy for renal cell
      carcinoma.

PMID- 17515072
TI  - [Bilateral maxillary sinus metastasis of renal cell carcinoma: a case report].
AB  - A 58-year-old man presented with lasting nasal obstruction. He had undergone
      right nephrectomy for renal cell carcinoma 11 years ago and right lobectomy for
      pulmonary metastasis 10 years ago. Paranasal sinus CT scans showed a soft tissue
      mass in the bilateral maxillary sinus. Abdominal CT showed left renal mass. Each
      mass was enhanced on the contrast-enhanced viewing. The paranasal mass biopsy was
      performed and resulted in profuse bleeding. Pathological examination was a
      metastasic renal cell carcinoma. After embolization of feeding artery, debulking
      surgery was performed. Postoperatively he was given radiotherapy and interferon
      therapy.

PMID- 17515073
TI  - A case of small cell carcinoma of the kidney.
AB  - A 47-year-old man had a retroperitoneal tumor measuring 18 cm in maximum diameter
      of the left kidney that was diagnosed with computed tomography (CT)-guided needle
      biopsy as small cell carcinoma. Microscopically, the tumor cells showed
      immunohistochemical reaction for neural cell adhesion molecule antibodies. This
      patient with advanced renal small cell carcinoma and multiple metastatic lesions
      was treated with the first-line combination chemotherapy of cisplatin, etoposide
      and ifosphamide, which showed a partial response of primary renal tumor and a
      complete response of liver metastasis, and with the second-line chemotherapy of
      cisplatin and irinotecan, which showed a complete response of Virchow's nodal
      metastasis. Thereafter, in spite of salvage chemotherapy of amurubicin
      hydrochloride for persistent and refractory renal small cell carcinoma, he died
      32 months after the first presentation due to local progression. However,
      combination chemotherapy of these anticancer agents made his prognosis more
      favorable than we expected before treatment. The extrapulmonary small cell
      carcinomas are generally known to be more aggressive and malignant than the lung
      small cell carcinomas, and small cell carcinoma arising from the kidney is an
      extremely rare malignant neoplasm, with only 34 cases reported in the English or
      Japanese literature. The prognosis of renal small cell carcinomas is currently
      limited as compared with the lung small cell carcinomas, and therefore a
      cumulative investigation of a larger number of cases treated with
      multidisciplinary modalities including combination chemotherapy is necessary.

PMID- 17515074
TI  - [A case of retroperitoneal malignant fibrous histiocytoma with marked response to
      concurrent cisplatin and radiation therapy: a case report].
AB  - A 42-year-old male was referred to our hospital with a complaint of right lumbar
      pain in September 1999. Abdominal computed tomography and magnetic resonance
      imaging revealed a large retroperitoneal tumor adjacent to the aorta and the
      renal vessels. We judged that it was inoperable. Then we performed percutaneous
      needle biopsy of the tumor. Histopathological examination showed a malignant
      fibrous histiocytoma (MFH). Two cycles of systemic chemotherapy with pirarubicin,
      vincritine and cyclophosphamide were ineffective, then we tried concurrent
      cisplatin and radiation therapy. Chemoradiation therapy showed a marked decrease
      in the size of the tumor, and the patient also recovered from right lumbar pain
      without serious side effects. After chemoradiation therapy, we performed
      tumorectomy. However, we could not curatively resect the residual tumor. He
      suffered from repeated recurrence and metastases of MFH afterwards. We performed
      repeatedly concurrent cisplatin and radiation therapy for the recurrent and
      metastatic tumor sites, and chemoradiation therapy led to regression of the
      tumors every time. However he died from liver dysfunction due to multiple liver
      metastases in May 2005. Concurrent cisplatin and radiation therapy might be an
      effective treatment for unresectable MFH.

PMID- 17515075
TI  - [Primary adenocarcinoma of renal pelvis and ureter suspected as metastatic tumor:
      a case report].
AB  - A 58-year-old man, who had undergone sigmoidectomy for sigmoid colon
      adenocarcinoma 3 years earlier, was referred to our clinic because of left
      ureteral tumor incidentally found by computed tomography (CT). Under the
      diagnosis of left ureteral carcinoma, retroperitoneoscopic left
      nephroureterectomy was performed. Pathological examination revealed
      adenocarcinoma of the left renal pelvis and ureter. Subtype of the adenocarcinoma
      was 'enteric type'. Five months later, urine cytology was positive and multiple
      non-papillary tumors were found on cystoscopy. By the transurethral resection of
      the tumors, bladder tumors appeared to be adenocarcinoma. Carefully considering
      the pathological findings and clinical course, we concluded that the tumor was
      not metastatic but primary adenocarcinoma followed by intravesical recurrence.

PMID- 17515076
TI  - [Leiomyoma of the urinary bladder treated by transurethral resection: a case
      report].
AB  - A 59-year-old woman with complaints of pollakisuria and dysuria, was referred to
      our hospital. Magnetic resonance imageing (MRI) revealed a tumor, about 59 mm in
      diameter. Cystoscopy showed a submucosal tumor covered with a normal mucosa.
      Histological diagnosis was leiomyoma of the urinary bladder by transurethral
      biopsy. So we performed complete resection of the tumor. To our knowledge, 30
      cases of leiomyoma of the urinary bladder by transurethral resection have been
      reported in the Japanese literature.

PMID- 17515077
TI  - [Molecular biology in diagnosis and treatment of lung cancer].
AB  - Progress in translational research for lung cancer achieved during the last 10
      years was reviewed. Since the discovery of oncogenes in 1980s, evidences of
      molecular basis of human cancer were rapidly accumulated and since the
      determination of draft sequences of human genome, the progress was further
      accelerated. With these molecular knowledge, it is now possible to
      comprehensively and extensively analyze human cancer using deoxyribonucleic acid
      (DNA) chips. The most remarkable event in this field was discovery of mutations
      of the epidermal growth factor receptor (EGFR) gene in a subset of patients with
      pulmonary adenocarcinoma with a high response to EGFR tyrosine kinase inhibitor.
      In the next 10 years, individualization of cancer treatment especially by
      targeted drugs based on molecular characteristics of each tumor using patients'
      tissue will be increasingly more important.

PMID- 17515078
TI  - [Surgical regeneration therapy using myoblast sheets for severe heart failure].
AB  - We have already reported that heart transplantation and left ventricular assist
      system (LVAS) are the useful surgical treatments for severe heart failure.
      However, these treatments have several problems such as donor limitation and
      complications and a novel strategy is desired. The autologous myoblast sheets
      attenuated the cardiac remodeling in the rat infarcted myocardium and dilated
      cardiomyopathy hamsters, leading to the improvement of cardiac performance. In
      this study, we will report the present results of heart transplantation and LVAS
      and also, report the development of porcine autologous myoblast sheets and
      hypothesized that autologous myoblast sheets regenerate the porcine infracted
      myocardium for clinical application. Skeletal myoblast (SM) isolated from leg
      muscle were cultured and detached from the dishes as single monolayer cell-sheet
      (tissue) at 20 degrees C using temperature-responsive culture dishes.
      Echocardiography demonstrated that cardiac systolic performance was significantly
      improved in SM group 4 weeks after operation rather than the control group. Both
      diastolic dysfunction and regional delayed relaxation in association with
      regional systolic function were recovered in the SM group, while the control
      group were not. Histologically, anterior wall was significantly recovered and
      dilatation of left ventricle was well attenuated in the SM group, while not in
      the other groups. SM-sheet implantation improved cardiac function by attenuating
      the cardiac remodeling and metabolic recovery in the impaired myocardium in the
      porcine ischemic myocardium, suggesting a promising strategy for clinical
      myocardial regeneration therapy.

PMID- 17515079
TI  - [Artificial heart].
AB  - Artificial heart or heart transplantation are required for the treatment of
      profound heart failure. Total artificial heart (TAH) and ventricular assist
      system (VAS) were developed from late 1950s and 2 extracorporeal pneumatic
      Japanese VASs (Toyobo VAS and Zeon VAS) were introduced to clinical field from
      1980. Now, over 850 patients were applied several types of VASs including
      Japanese VASs. And 80% of heart transplant recipients were supported by VASs for
      714 days (mean). Small size implantable left VAS (LVAS) are required and several
      types of non-pulsatile pump, including 2 Japanese made centrifugal pumps, are
      under clinical trials. And destination therapy by using implantable pulsatile
      LVAS for end-stage heart failure patients has been started in United States and
      is performed in United States and Europe. In near future, artificial heart and
      heart transplantation will be selected according to the conditions of the
      patients with profound heart failure.

PMID- 17515080
TI  - [Allo- and xeno-transplantation].
AB  - Organ transplantation is now effective therapies across a wide range of both
      fatal and non-fatal diseases. The excellent survival and success rates of organ
      transplantation have led to high levels of demand globally. The demand has
      outstripped the supply of organs from both deceased donors and from the
      altruistic living relatives of patients in need. Increasing use, over the past 10
      years, of living donation of nonregenerative organs has extended from kidneys to
      livers, lungs and pancreas in some instances, despite the hope that reliance on
      living donors could be reduced. And, it is clear that ethically-unacceptable
      practices occur in a number of countries. The 1991 World Health Organization
      (WHO) Guiding Principles (GP) have influenced national legislation and
      professional codes but over the last 10 years many transplantation practices are
      no longer in line with the GP. The GP will be revised in 2008. While
      xenotransplantation offers a potential solution to the demand, 3 problems need to
      be overcome, i.e. inadequate physiological function, rejection of the graft, and
      the risk of transmitting a serious and/or novel infectious disease to the human
      recipient and wider public.

PMID- 17515081
TI  - [The system problems related to thoracic surgery practices in japan; message from
      the Japanese association for thoracic surgery].
AB  - The thoracic surgery practice in Japan has characteristics such as strong burden
      to surgeons and young trainees for high-risk procedures under poor health care
      manpower system and less qualification for their high-level practices. The
      presence of too many numbers of certified surgeons and teaching hospitals for
      cardiac, general thoracic and esophageal surgeries has been well recognized
      providing low quality maintenance and poor training system. The Japanese
      Association for Thoracic Surgery has recently made a step towards to open the
      data of hospital quality promoting the discussion to reunify the hospitals and
      surgeons into reasonable numbers to respond to the social demand. The new 2-year
      postgraduate clinical training and also a new specialty medical board approval
      for advertisement have provided various problems and controversies, and we must
      make efforts to overcome these problems by providing new strategies to make our
      practices more qualified.

PMID- 17515082
TI  - [How to make our graduate/postgraduate training in thoracic surgery further
      attractive].
AB  - Graduate and postgraduate education in the specialty of cardiovascular and
      general thoracic surgery may become more attractive by turning by itself to focus
      on producing competitive specialists and by having mature specialty boards to aim
      at. For this to accomplish consensus must be formed among hospital surgeons who
      are now united through specialty associations. In our country specialists may
      reasonably be less than 1000 in number in each thoracic specialty to call for
      specialist doctor's fee.

PMID- 17515083
TI  - [Recent 10-year progress of board certificated cardiovascular surgeon].
AB  - The recent 10-year progress and prospective views of the Board Certificated
      Cardiovascular Surgeon in Japan were described. Although total framework of the
      Japanese Board of Medical Specialist is not yet established, the certification
      standards of the Board Certificated Cardiovascular Surgeon and training hospital
      were substantially revised in 2005 and 2006 for increasing those quality.
      Hereafter, we should tackle to make new systems for the trainee's registration,
      gaining of incentive for the Board Certificated Cardiovascular Surgeon, and
      education of coworkers in surgical fields.

PMID- 17515084
TI  - [Establishment of the Japanese Board of General Thoracic Surgery].
AB  - The process of establishment of the Japanese Board of General Thoracic Surgery
      (JBGTS) during the past decade was overviewed chronorogically. It was established
      and became effective in 2004 by conjoint of the Japanese Association for Thoracic
      Surgery with the Japanese Association of Chest Surgery. Eleven handreds and 43
      surgeons have already been certified at the present time. However, the system is
      planning to be revised in 2009 in order to improve the quality of the residency
      program. Continuing efforts to improve the system is required in cooperation with
      Japanese Board of Medical Specialties.

PMID- 17515085
TI  - [International communications and exchanges in cardiothoracic surgery].
AB  - The importance of international communications and mutual exchanges have become
      more vital than ever in every field including our specialty of cardiothoracic
      surgery. The communications should be not only on individual or institutional
      bases but also at the level of academic Societies. The Asian Society for
      Cardiovascular Surgery has played a critical role as the key Society on the third
      pole of the globe to communicate with the organizations in other continents, such
      as the European Association for Cardiothoracic Surgery, the American Association
      for Thoracic Surgery, the Society of Thoracic Surgeons as well as Cardiothoracic
      Surgery Network (CTSNet). In order for the Japanese cardiothoracic surgeons to
      continue to be respected and hold the leadership in Asian community of our
      specialty, it is mandatory to promptly improve the domestic problems concerning
      the postgraduate training of cardiothoracic surgeons.

PMID- 17515086
TI  - [Cardiac surgery in Japan from a view of Germany].
AB  - In Germany, standards of facilities for cardiovascular surgery are established
      under the guidance of the Ministry of Health and Welfare, and numbers of
      hospitals are regulated for the needs of patients. Not only in Germany but in
      many countries of Europe, it is reasonable by a number of patients 1 to 1 million
      population. A number of cardiac operations in 1 authorized institution in Germany
      is 10 times as that of Japan. In this condition, I'll introduce the medical care
      systems of Germany; postgraduate education system for both medical specialists
      and home doctors, introduction of private insurance system based on National
      Health Insurance system for everyone, and a release of medical information,
      quality control, acknowledged not by an own declaration but by the third
      organization.

PMID- 17515087
TI  - [Japanese thoracic surgery; a view from the United States].
AB  - Ten years ago, I attempted to make a prospective over-view on the future of
      Japanese thoracic and cardiovascular surgery in this journal. Similarly, I am
      giving a perspective on the same subject from the American point of view. The
      steady increase in Japanese contribution to the 2 peer-reviewed American journals
      is impressive. The membership in the Society of Thoracic Surgeons also shows a
      significant growth among Japanese surgeons. Presentations in the recent
      professional meetings by the Japanese thoracic surgeons has increased, both in
      numbers and in quality. Their strength is seen in lung cancer, aortic surgery,
      congenital heart defects, and basic science fields. They are also moving toward
      establishing standards in postgraduate training and in the practice of their
      specialty. The current effort for creating a data-base in their fields is well
      appreciated by the western hemisphere. Finally, their cooperation with other
      Asian and Pacific colleagues deserves praise from the U.S. as well. It is my
      humble opinion that the Japanese thoracic and cardiovascular surgery has reached
      the matuirity and is ready to produce abundant fruits.

PMID- 17515088
TI  - [Current concepts in perioperative management of children : preface and
      comments].
AB  - In the past few years, pediatric anesthesia management changed rapidly to more
      evidence-based and patient-oriented practice. It has been emphasized that
      "focused and individualized" pre-anesthesia evaluation is preferred to routine
      screening of laboratory tests and X-rays. Anesthesia induction should be less
      stressful for children through the use of various approaches, such as
      preoperative preparation, sedative premedication, and parent-present induction.
      Cuffed tracheal tube is becoming popular for small children, and its indication
      should be considered individually. Laryngeal mask airway is frequently used for
      simple short cases. Perioperative fluid infusion therapy has been a controversial
      issue. Traditional therapeutic regimen using hypotonic solution with glucose is
      criticized as a result of the growing evidence of hyponatremia and hyperglycemia.
      New ventilatory modes and sedative medications are now available for pediatric
      patients, and lung-protective ventilatory strategy should be considered to
      protect immature lung from ventilator-induced lung injury. Emergence agitation
      from general anesthesia is an evolving problem. Sevoflurane is known to be a
      major risk factor for stormy wake-up. Pediatric anesthesiologists should pursue
      high quality of anesthesia emergence. All anesthesia residency programs should
      include pediatric rotation; otherwise anesthesia residents will lose
      opportunities to learn basic concepts of pediatric anesthesia.

PMID- 17515089
TI  - [Preoperative evaluation in children].
AB  - It is important to evaluate medical history and to examine physical findings for
      preventing the complication during perioperative period. The communication among
      the medical staffs, and the explanation to the patients and family are also
      important. A different approach from the adult is necessary for infant's
      preoperative assessment. The problems encountered in specific disease for
      children were described.

PMID- 17515090
TI  - [Induction of general anesthesia in pediatric patients].
AB  - The induction of general anesthesia is one of the most stressful procedures
      during the perioperative period for pediatric patients. Postoperative negative
      behavioral changes, such as nightmares or separation anxiety are reported in the
      children undergoing general anesthesia. To avoid these problems, the
      anesthesiologists have to pay more attention to the psychological needs of young
      patients as well as the technical aspects. Preoperative interview is important to
      identify the child who has extreme fear and anxiety. Premedication with sedatives
      and psychological preparation are effective for the smooth induction. In this
      article, preparation for the induction and practical skills of the induction in
      children, newborns, as well as patients with difficult airway and with full
      stomach are summarized.

PMID- 17515091
TI  - [Reappraisal of perioperative fluid therapy in children].
AB  - Two recently recognized issues are reviewed ; one is a hospital acquired
      hyponatremia in children treated with intravenous hypotonic maintenance fluids
      and the other is the pros and cons of glucose addition to these fluids. Children
      in the perioperative period are at risk for nonosmotic secretion of ADH and
      stress-induced insulin resistance, which necessitate reducing the volume of
      maintenance fluid to half the previously recommended volume, and the
      concentration of additive glucose to approximately 2%. While isotonic fluids are
      recommended intraoperatively, controversies still exist on the constitution of
      maintenance fluids in the postoperative period, where the choice of an isotonic
      solution should be more pertinent to that of a hypotonic solution, but evidence
      is weak ; further investigations are needed to make a decision.

PMID- 17515092
TI  - [Pediatric airway management : cuffed endotracheal tube and other devices for
      tracheal intubation].
AB  - Uncuffed endotracheal tubes have been commonly used in pediatric patients, but
      cuffed pediatric endotracheal tubes are recently introduced and stirred up a
      controversy. Uncuffed tubes may require multiple laryngoscopies, pollute the
      environment, and cause pulmonary aspiration as well as unstable ventilation. A
      recent study revealed that the contours of the airway and the tracheal tube are
      different, so that the pressure exerted on some parts of the cricoid mucosa may
      not be appropriate. Cuffed endotracheal tubes overcome these shortcomings if
      anesthesiologists pay close attention to the insertion length of the tube and
      cuff pressure. Laryngeal mask airway has worked well, with few complications, as
      a ventilatory device in pediatric patients whose tracheas cannot be intubated
      and/or whose lungs cannot be ventilated with conventional techniques. It is also
      used for a conduit for fiberoptic intubation and emergent airway with patients in
      the prone position. The lightwand (Trachlight) is another device for pediatric
      intubation and is recommended as the first-line option in patients who can be
      ventilated but in whom laryngoscopic intubation has failed. AirWayScope (Pentax
      AWS) is a novel intubation device which combines an airway, camera and monitor It
      can be an epoch-making intubation device for infants and children if a smaller
      size is available in the future.

PMID- 17515093
TI  - [Post-operative respiratory management in infants].
AB  - Regarding postoperative respiratory management in infants, their postoperative
      circulatory and respiratory conditions are quite different among medical centers.
      The lung functions of infants are still immature. Respiratory rate of infants
      decreases from the birth (just after birth ; 47, 12 months ; 26 cycles x mimute(
      1)). Tidal volume increases with body weight (just after birth ; 23.8, 12 months
      ; 89.1 ml), and tidal volume per body weight is constant (6.9-9.0 ml x kg(-1)).
      When we perform postoperative respiratory managements, we must discuss the
      ventilatory mode to use, permissible airway pressure, and values of blood gas
      analysis among postoperative care team. In infants with acute lung injury, we
      should select high frequency oscillation (HFO) according to lung protective
      ventilatory strategy theory (low tidal volume+open lung approach).

PMID- 17515094
TI  - [Emergence agitation in pediatric anesthesia].
AB  - Emergence agitation following general anesthesia in children is an evolving
      problem, since sevoflurane has become a popular anesthetic for pediatric
      anesthesia. Several studies comparing incidence of emergence agitation between
      halothane and sevoflurane showed that sevoflurane anesthesia would result in
      higher chance of emergence agitation. The reasons of higher incidence of
      emergence agitation following sevoflurane anesthesia remain unknown. Other risk
      factors of emergence agitation include age of patients, operative procedure,
      pain, preoperative anxiety and so on. Several methods are advocated to prevent
      emergence agitation. The aggressive treatment of surgical pain is essential to
      avoid screaming on emergence. In addition, varieties of medication, including
      opioid, sedatives and alpha-2 agonist, have been tried with various success. The
      avoidance of sevoflurane use for maintenance of anesthesia could be a major
      contributing factor to reduce the risk of emergence agitation. In the light of
      quality of emergence, propofol anesthesia seems to be favorable for sedation in
      imaging procedures. Emergence agitation should be treated appropriately, since it
      could injure the patient him/herself or caregiver. The calm wake-up from general
      anesthesia will greatly enhance the parental satisfaction to anesthesia and
      surgery.

PMID- 17515095
TI  - [Anesthetic management for patients with compromised left ventricular function
      due to coronary artery disease in non-cardiac surgery].
AB  - BACKGROUND: As the number of patients suffering from coronary artery disease
      (CAD) increases, anesthetic management for these patients become more common than
      the past. But no established management strategies have been proven beneficial.
      METHODS: We reviewed all anesthetic management records of seven patients with
      compromised LV function (EF<30% or FS<30%) for CAD in our hospital, who had
      undergone non-cardiac operations. RESULTS: Three cases were brain surgeries and
      four cases were abdominal surgeries. In all cases, central venous catheters were
      placed before induction of general anesthesia. After inotropic agents were
      started through central venous catheters, patients went through induction with
      midazolam, fentanyl and propofol without any trouble. In three cases of abdominal
      surgeries, pulmonary artery catheters were placed. And in five cases, artery
      catheters were placed in the femoral arteries, so that, in case of cardiac shock,
      we could start IABP without delay. In one case, we experienced shock during
      operation, but without IABP, the patient recovered with pharmacological support.
      No patient died of cardiac cause during the hospital stay for the procedure.
      CONCLUSIONS: We reported anesthetic management of seven patients with compromised
      left ventricular function for CAD in non-cardiac surgery. However, as the reports
      of anesthetic management in patients with compromised left ventricular function
      in non-cardiac surgery is few, further study will be required.

PMID- 17515096
TI  - [Fiberoptic intubation through laryngeal mask airway with an innovated tube under
      5% sevoflurane anesthesia].
AB  - BACKGROUND: Previously we had reported an intubation method using 52 cm innovated
      tube (I. D.=5.0) for patients with difficult airways, but hemodynamic change and
      anesthetic level were not evaluated during this procedure. In the present report
      we investigated heart rate, mean arterial pressure and bispectral index (BIS)
      during this procedure under volatile induction and maintainance of anesthesia
      (VIMA) with 5% sevoflurane without muscle relaxant. METHODS: We enrolled 6
      patients considered having difficult airway. Airway management was performed
      under VIMA of 5% sevoflurane. After insertion of a laryngealmask airway (LMA), 52
      cm-tube was intubated through LMA under bronchofiberscope. After LMA was removed,
      the endotracheal tube was passed through the 52 cm-tube into the trachea.
      Hemodynamic change was recorded at 1 min intervals and BIS at 5 sec intervals
      until 3 min after securing their airways. RESULTS: VIMA of 5% sevoflurane
      provides stable hemodynamic state during the procedure and suppressed body
      movement sufficiently on tracheal intubation. BIS was elevated due to cough on
      intubation in 4 cases. However no patient recalled the procedure. CONCLUSIONS:
      Sevoflurane 5% suppressed hemodynamic changes sufficiently with this procedure
      without muscle relaxants.

PMID- 17515097
TI  - [Dexmedetomidine is a useful concomitant anesthetic agent for perioperative
      management during tracheobronchial Dumon stent surgery].
AB  - We treated 2 patients, 1 undergoing placement and 1 removal of a tracheobronchial
      Dumon stent, both of whom required preservation of spontaneous breathing during
      the perioperative period to avoid life-threatening hypoxemia, with
      dexmedetomidine (DEX) as an anesthetic adjunct. In both cases, anesthesia was
      induced with 6 microg x kg(-1) x hr(-1) of DEX for 10 minutes and then maintained
      at 0.4-0.8 microg x kg(-1) x hr(-1), along with a target controlled infusion of
      propofol combined with intermittent administrations of low-dose fentanyl. Muscle
      relaxants were avoided and spontaneous breathing was preserved throughout the
      surgical procedures. The airway was secured using a rigid bronchoscope specific
      for a Dumon stent procedure. No rescue device, such as high frequency jet
      ventilation or a percutaneous cardiopulmonary support system, was needed. The
      perioperative courses were uneventful without any pulmonary or cardiovascular
      complications. DEX has potent sedative, amnesic, and analgesic properties with a
      low respiratory depressant effect. Therefore, it is considered useful as a
      concomitant anesthetic agent for perioperative management of patients who require
      preservation of spontaneous breathing.

PMID- 17515098
TI  - [Perioperative management for cesarean section in a patient with pulmonary
      thromboembolism due to deep venous thrombosis].
AB  - It has been estimated in Japan that Western-life style increases maternal
      mortality because of pulmonary thromboembolism (PTE). We report a 29-year-old
      primipara who suffered PTE due to deep venous thrombosis (DVT) in her 29th weeks'
      gestation. Except for slight tachypnea, she was relatively stable.
      Anticoagulation with heparin was started immediately. The retrievable inferior
      vena cava filter (IVC-F) was inserted. Four hours before surgery with
      discontinuation of heparin, the cesarean section was performed under general
      anesthesia. We used transesophageal echocardiography, a pulmonary artery catheter
      and end tidal CO2 monitoring for early detection and rapid management of
      recurrent PTE. She had no trouble during operation and her baby was born without
      serious symptoms. After recovery from anesthesia, she was admitted to the
      intensive care unit. Heparin was restarted after confirmation of hemostasis. On
      the 3rd postoperative day, we started thrombolytic therapy with urokinase which
      was tapered off during a week. Heparin was switched to warfarine gradually. On
      the 10th postoperative day, IVC-F could not be removed because of remaining DVT.
      She was discharged on daily warfarine. We experienced the perioperative
      management for cesarean section at 29 weeks' gestation following PTE due to DVT.

PMID- 17515099
TI  - [Pain control by caudal epidural infusion in a pregnant woman with hemorrhoids
      carrying triplets].
AB  - A 30-year-old woman in her 25th week of gestation with triplets complained of
      severe pain due to a hemorrhoid. The patient felt it was difficult to continue
      childbearing. First we performed caudal epidural block with 0.25% bupivacaine 20
      ml and morphine hydrochloride 2 mg once a day, for 12 days without inserting a
      catheter because there were signs of infection. After the signs of infection had
      disappeared, we inserted a caudal epidural catheter and administered 0.125%
      bupivacaine 1-2 ml x hr(-1) for 6 days, up to the day of cesarean section. Liver
      function and blood bupivacaine levels of the mother were acceptable in the
      perioperative periods. The babies' Apgar scores and neurologic findings of the
      babies were normal. Blood bupivacaine levels of the babies were below the limit
      of measurement.

PMID- 17515100
TI  - [Landiolol prevented myocardial ischemia in a patient with severe aortic stenosis
      undergoing total gastrectomy].
AB  - Gastric cancer was detected in a 71-year-old man with severe aortic stenosis.
      According to ACC/AHA guidelines, aortic stenosis in the patient was so severe
      that noncardiac surgery was considered appropriate only after aortic valve
      replacement. However, due to uncontrollable hemorrhage from gastric cancer, total
      gastrectomy was urgently required. Surgery was performed under epidural and
      general anesthesia. Blood pressure and heart rate were stable during anesthetic
      induction, tracheal intubation and skin incision. Just after peritoneal incision,
      however, ST decreased significantly following hypertension and sinus tachycardia,
      which were controllable by deepening of the anesthetic level. This ST depression
      was dependent on heart rate but not blood pressure. Therefore, in order to
      control the heart rate and prevent myocardial ischemia, low dose landiolol was
      infused prophylactically. This agent regulated the heart rate below 85 beats per
      minute without inducing hypotension and prevented myocardial ischemia during the
      remaining anesthetic course including extubation and recovery from anesthesia.
      Although beta blocker is not generally recommended in patients with aortic
      stenosis, present case suggests that landiolol is effective and useful to prevent
      cardiac ischemia even in a patient with severe aortic stenosis.

PMID- 17515101
TI  - [Emergent operation for a patient of duodenal bleeding accompanied with fulminant
      myocarditis].
AB  - A 53-year-old woman developed general fatigue following an upper airway
      infection, which abruptly progressed to cardiogenic shock showing systolic blood
      pressure of 60 mmHg. An echocardiography revealed an ejection fraction of 0.11,
      diffuse severe hypokinesis and left ventricular thrombosis. Fulminant myocarditis
      was suspected, and intensive care including mechanical ventilation, intraaortic
      balloon pumping (IABP), catecholamine support and anticoagulation therapy was
      initiated immediately. Although the cardiac function gradually recovered, she
      developed a duodenal bleeding on the third therapeutic day. Factors such as low
      output syndrome, heparinization, steroid pulse therapy and platelet dysfunction
      due to IABP can enhance the hemorrhagic tendency. Since it was difficult to
      control bleeding by the endoscopy, blood transfusion was performed, and the
      operation was planned on the 13rd day when the cardiac function seemed to have
      recovered enough. The patient was anesthetized with ketamine, propofol and
      fentanyl. To maintain stable circulation, circulatory parameters such as blood
      pressure, central venous pressure, and cardiac output were monitored. After a
      preoperative consultation with the surgeon, the surgical technique had been
      preoperatively decided to reduce the surgical stress, and then partial
      duodenosectomy and gastro-jejunum anastomosis was performed. She was discharged
      on the 38th post operative day without complications. In cases of hemorrhagic
      disease accompanied by an acute phase of fulminant myocarditis, consultation
      among surgeons, cardiologists and anesthegiologists should be mandatory to
      determine the timing of the operation and to decide the degree of surgical
      invasion.

PMID- 17515102
TI  - [Anesthetic practices and use of brain protective therapies for cerebral aneurysm
      surgery in Japan].
AB  - We surveyed anesthetic practices and the use of cerebral monitoring and brain
      protective therapies during cerebral aneurysm surgery by sending a questionnaire
      to 822 hospitals in Japan. Three hundred and fifty four hospitals responded. For
      induction, 51% used thiopental, 41% used propofol, and 94% supplemented induction
      with fentanyl. For maintenance 45% used isoflurane, 29% used sevoflurane, and 26%
      used propofol. Only 6% used EEG and/or evoked potentials in most of their
      patients. Specific brain protective measures were used in most of the hospitals.
      If used, 97% used mannitol, 43% used steroids and 23% used a certain level of
      induced hypothermia. When mild hypothermia was used, 39% used 33-34 degrees C,
      59% used>34 degrees C, 2% used <33 degrees C, and only 4% used mild hypothermia
      in every patient. During temporary clipping, 18% kept the blood pressure equal to
      the level when awake, while 56% used induced hypotension. To control blood
      pressure during extubation, 72% used nicardipine or nitroglycerine. The use of
      intraoperative brain protective therapies were common but brain monitoring was
      not the standard.

PMID- 17515103
TI  - [Training of endotracheal intubation for an emergency medical technician and
      three cases of endotracheal intubation during emergency situation].
AB  - It is said that airway management is an important part of lifesaving at the
      prehospital care for a seriously ill emergency patient. We performed the training
      of endotracheal intubation for an emergency medical technician, and in this
      report we discussed the results of trainings and examined 3 cases of endotracheal
      intubation in the emergency situation after training. Various kinds of problem
      arose through this training, for example, difficulty to get the consent from
      patients, overlap of a case for clinical resident and emergency medical
      technician, large responsibility of the anesthesiologist as a teaching staff. In
      addition, there may be no useful case for lifesaving at the emergency situation
      in 3 cases of endotracheal intubation. We consider that it may be difficult, but
      possibility cannot deny if endotracheal intubation by emergency medical
      technicians contribute to lifesaving rate improvement from viewpoint of
      prehospital care.

PMID- 17515104
TI  - [Essential orthopedics knowledge for disaster relief].
AB  - In Pakistani earthquake of 2005, there were many wounded patients needing
      orthopedic care. I present in this article the essential orthopedics knowledge,
      which is necessary for anesthetists in disaster area. The wound treatment
      consists of debriedment and delayed primary closure. Fracture of bone is mainly
      treated conservatively. Fractures of clavicle, or arm bones are treated with
      clavicle band, plaster of Paris or triangular bandage, and fractures of leg bones
      with traction. In the use of antibiotics, it is necessary to keep in mind that
      antibiotics do not reach the tissue if its blood circulation is poor.

PMID- 17515105
TI  - [Development of a new estimation method of ingestion time to suspected food in
      food-poisoning outbreaks].
AB  - In food-poisoning outbreaks, the ingestion time of suspect foods has been
      estimated using the Sartwell method (Hirayama method), the graphical method and
      maximum likelihood estimation. These methods are based upon the assumption that
      the incubation period is log-normally distributed. However, these methods may not
      always be valid because the bias and variability of the estimates are large. We
      constructed a database from 341 food-poisoning cases in the literature. Using
      this database, we developed a method to estimate the actual ingestion time based
      on the period from the ingestion time to the first outbreak, using a multiple
      linear regression equation. Since only 9.09% of cases showed log-normal
      distribution, the above three methods would not be valid in most cases. The new
      method was applicable in all cases. In addition, the values estimated by the new
      method showed higher correspondence and accuracy than the values estimated by the
      other methods. Therefore, we consider that the new method is superior to those
      methods.

PMID- 17515106
TI  - [Survey of pesticide residues in rice (April, 1995-March, 2005)].
AB  - Pesictide residues in 343 samples of domestic rice and 32 samples of imported
      rice purchased on the Tokyo market from April 1995 to March 2005 were
      investigated. Residues of eleven kinds of pesticides (including organophosphorus,
      organochlorine, carbamate, pyrethroid and organonitrogen pesticides and bromide)
      were detected at levels between trace and 1 ppm in 47 domestic rice samples. DDVP
      and bromide residues were detected at levels between 0.01 ppm and 5 ppm in 18
      imported rice samples. For rice samples that were found to containing pesticides,
      the amounts of pesticide intake were calculated according to the daily intake of
      rice, and they were compared with the ADI values. Since residual pesticide levels
      were 17/10,000-2/5 of ADI, all the rice samples were considered to be safe for
      human consumption.

PMID- 17515107
TI  - [Human hepatitis viruses A, B, C, D and E: particularly on A and E in view of
      food hygienics].

PMID- 17515108
TI  - [Microbiological contamination of wheat, wheat flour, and dough and fresh noodles
      made from wheat flour: a literature survey].

PMID- 17515109
TI  - [Biologic base of anxiety disorders: recent progress].
AB  - We reviewed recent knowledge and a biologic base of anxiety disorders. As for
      brain image study, mainly study on PET, fMRI and NIRS has advanced. The neural
      circuit hypothesis of Gorman still attracts attention. We will think that
      characteristics of each anxiety disorder disease will become clear from these
      studies in future. We think that a genetic role will be associated with
      personality, character and gene study. We mention the connection between
      neuropeptides and anxiety in animal experiments. In addition, the past sensory
      stimulation in the amygdala, regarded as the center of anxiety, and the
      reinforcement of emotional ties is pointed out as an important thing for anxiety
      formation.

PMID- 17515110
TI  - [Mucosal immunotherapy for alzheimer's disease with viral vectors].
AB  - Alzheimer's disease is characterized by progressive loss of cognitive function
      due to amyloid-l (Al) deposits in the central nervous system. Based on the
      amyloid cascade theory, many reports indicated that immunotherapy is effective
      for the treatment of Alzheimer's disease. We developed a mucosal immunotherapy
      for Alzheimer's disease via oral vaccine with recombinant adeno-associated virus
      (AAV) vector and nasal administration of recombinant sendaivirus vector
      expressing Al 1-43/IL-10. Oral or nasal administration of recombinant virus
      vector induced the long-term expression of All in the epithelial cells and
      presented the Ap antigen to the mucosal immune system. Antibody levels in the
      mouse serum were elevated after 4 weeks and the antibody inhibited the
      aggregation of Ap in vitro. Immunohistochemistry of the APP transgenic mouse
      brain tissue showed that All burdens were markedly decreased in the treated mouse
      compared to the control. The inflammation was not recognized in any organ
      including brain and kidney. Mucosal immunotherapy with viral vectors
      significantly cleared the Ap depositions without inflammation and reduced the
      levels of Al in the brain homogenates of APP transgenic mice; therefore, it might
      be effective for the treatment of Alzheimer's disease.

PMID- 17515111
TI  - [Inhibition of neuronal death by promoting degradation of intracellular amyloid
      beta-protein].
AB  - Inhibition of aggregation of amyloid p-protein (AP) and promotion of
      extracellular AM removal are known as potent therapeutic tools for Alzheimer's
      disease (AD). While, the importance of Af342 accumulating in neurons has recently
      been suggested, and we have reported that A/42 accumulating in the neurons moves
      into the nucleus, activating p53 mRNA expression and leading to apoptosis (Ohyagi
      et al, FASEB J, 2005). Moreover, intraneuronal Ap is reported to induce
      mitochondrial dysfunction via binding ABAD, synaptic pathology, and inhibition of
      proteasome. Thus, it is an alternative therapeutic tool to decrease the levels of
      A342 and p53 proteins in AD neurons. We established a human neuroblastoma (SH
      SY5Y) cell culture system in which AV peptide is artificially accumulated in
      cytosol. We have found that apomorphine hydrochloride promotes degradation of
      intracellular AM and p53 attenuating oxidative stress-induced apoptosis. Using a
      proteasome activity assay method, one of the mechanisms is thought to be
      activation of proteasome. Similar anti-apoptotic effect was observed in the
      primary cultured neurons. Apomorphine hydrochloride is now used as a dopamine
      agonist for Parkinson's disease or an anti-ED drug in western countries, but also
      may be one of the candidate drugs to inhibit neuronal death in AD.

PMID- 17515112
TI  - [A molecular chaperone inducer as potential therapeutic agent for
      neurodegenerative disease].
AB  - Recent reports have shown that ER stress is involved in the pathology of some
      neurodegenerative diseases. In a screen for compounds that induce the ER-mediated
      chaperone BiP/GRP 78 (BiP), we identified BiP inducer X (BIX). BIX induced BiP
      only, in a dose-dependent manner, without induction of other molecules involved
      in the ER stress response. Pretreatment of neuroblastoma cells with BIX reduced
      cell death induced by ER stress. Intracerebroventricular pretreatment with BIX
      reduced the area of infarction due to focal cerebral ischemia in mice. In the
      penumbra of BIX-treated mice, ER stress-induced apoptosis was suppressed, leading
      to a reduction in the number of apoptotic cells. Taken together, BIX induces BiP
      to prevent neuronal death by ER stress, suggesting that it may be a potential
      therapeutic agent for cerebral diseases caused by ER stress.

PMID- 17515113
TI  - Changes in central dopaminergic systems with the expression of Shh or GDNF in
      mice perinatally exposed to bisphenol-A.
AB  - In the previous study, we reported that exposure to bisphenol-A induced the
      potentiation of dopamine receptor functions in the mouse limbic area, resulting
      in supersensitivity to methamphetamine-induced pharmacological actions. The
      present study was undertaken to investigate whether prenatal exposure to
      bisphenol-A could produce morphological change in dopaminergic neuron and the
      pattern of expression of genes regulating the dopaminergic neuron development.
      Here we found that prenatal and neonatal exposures to bisphenol-A increased the
      tyrosine hydroxylase- and dopamine transporter-like immunoreactivities in the
      adult mouse limbic area. The present molecular biological study shows that
      chronic bisphenol-A treatment produced a significant decrease in the dopaminergic
      neuron development factors, sonic hedgehog and glial cell line-derived
      neurotrophic factor, which were also decreased by prenatal exposure to bisphenol
      A. These results suggest that chronic exposure to bisphenol-A could disrupt the
      dopaminergic neurotransmission in the process of dopaminergic neuron development.

PMID- 17515114
TI  - [Effect of estrogen on nucleotide excision repair of N2a neuroblastoma cells].
AB  - Until now reduced estrogen level has been considered to affect some psychiatric
      symptoms, because there are sex differences in onset of Schizophrenia and
      Alzheimer's disease. Estrogen is associated with cognitive functions, and it has
      been reported to protect oxidative damage of DNA related to base excision repair
      (BER). Some patients with Xeroderma Pigmentosum, who have normal BER and impaired
      nucleotide excision repair (NER), are known to be suffering from mental
      retardation. Therefore we hypothesized that impaired NER was partly associated
      with pathology of mental disorder and investigated the effects of estrogen on NER
      for ultraviolet-induced DNA damage. The N2a neuroblastoma cell line was used as a
      representative of neuronal cells and 17p-estradiol was selected as one of the
      most active estrogen derivatives. There were no significant effects of 17p
      estradiol on prevention of DNA damage, promotion of DNA repair, or cell survival
      at the concentration of 0-0.1 microM 17p-estradiol (below cytotoxicity level).
      These results described that estrogen might not directly affect NER except
      through another DNA repair system.

PMID- 17515115
TI  - [Molecular basis of Hodgkin lymphoma and anaplastic large cell lymphoma and
      molecular targeting therapy by an NF-kappaB inhibitor].

PMID- 17515116
TI  - [CCR4 as a molecular target for novel immunotherapy in malignant lymphoma].

PMID- 17515117
TI  - [Febrile neutropenia].

PMID- 17515118
TI  - [Prevention, diagnosis, and treatment of viral infections in patients with
      hematologic diseases].

PMID- 17515119
TI  - [Evidence-based infection control].

PMID- 17515120
TI  - [Early blastic transformation within a year of imatinib treatment in 2 cases of
      chronic myeloid leukemia].
AB  - We report herein on two rare cases of newly diagnosed chronic myeloid leukemia,
      which developed early blastic transformation within a year of imatinib treatment.
      Case 1 is a 22-year-old Japanese female, who underwent gradual blastic
      transformation with the increase of a resistant clone, which cytogenetically
      evolved right after she reached complete hematologic remission. Case 2 is a 24
      year-old Japanese male, who underwent sudden transformation after 8 months
      treatment with imatinib mesylate following complete cytogenetic response.
      Although a sudden blastic transformation is extremely rare, the occurrence of
      such events even among the low-risk, good responding patients highlights the need
      for continued, rigorous monitoring by sensitive analysis, such as quantitative
      PCR. In order to accomplish the early eradication of minimal residual disease,
      the therapeutic strategy for chronic myeloid leukemia has to be defined in the
      era of imatinib, considering the application of allogeneic stem cell
      transplantation, which is currently the only curative treatment.

PMID- 17515121
TI  - [Successful treatment with L-asparaginase-based combination chemotherapy for
      refractory T-cell post-transplant lymphoproliferative disorder].
AB  - A 31-year-old man underwent kidney transplantation in 1996, and had been on
      immunosuppressants. In 2005, he presented with discomfort on swallowing. Swelling
      of the left tonsil and a mediastinal mass were observed. A biopsy of the left
      tonsil showed a monotonous proliferation of atypical lymphocytes suggesting post
      transplant lymphoproliferative disorder (PTLD). The reduction of
      immunosuppressants did not result in any clinical improvements, and he developed
      bilateral cervical lymphadenopathy. A biopsy of the cervical lymph node also
      showed monotonous proliferation of TdT, CD3, CD5, CD7, CD10, and CD34-positive
      immature cells. T-cell receptor rearrangement, but not EBER, was detected. Based
      on these findings, monomorphic T-cell PTLD was diagnosed. He was treated with
      four different chemotherapeutic regimens without any clinical improvements, and
      the PTLD became leukemic. Chemotherapy consisting of L-asparaginase, vincristine,
      and dexamethasone (LVD) was then given, which resulted in massive tumor lysis.
      However, after two courses of LVD, complete remission was achieved. T-cell PTLD
      is a rare disorder, characterized by its refractoriness to chemotherapy as
      opposed to B-cell PTLD. Our experience suggests that L-asparaginase-based
      chemotherapy may improve the prognosis of T-cell PTLD.

PMID- 17515122
TI  - [Acute promyelocytic leukemia associated with hemophagocytic syndrome].
AB  - A 19-year-old man was referred to our hospital with pancytopenia and disseminated
      intravascular coagulation (DIC). Bone marrow aspiration revealed 93.6% of
      atypical promyelocytes and marked hemophagocytosis by macrophages. The diagnosis
      of acute promyelocytic leukemia (APL) associated with hemophagocytic syndrome
      (HPS) was made. As there was no evidence of infection, collagen diseases, or
      abuse of medicine, his HPS was classified as malignancy-associated HPS (MAHS).
      The DIC improved after administration of idarubicin and all-trans-retinoic acid
      (ATRA). On the 11th day, however, DIC and elevation of serum LDH recurred with
      the appearance of hepatosplenomegaly. Although APL cells had decreased in the
      bone marrow, hemophagocytes persisted. After administration of dexamethasone and
      etoposide, DIC and HPS improved, and complete remission of APL was obtained. ATRA
      was implicated in the aggravation of APL-induced MAHS in the present case.

PMID- 17515123
TI  - [Alveolar rhabdomyosarcoma of unknown origin mimicking acute leukemia at the
      initial presentation].
AB  - A 14-year-old boy presented with a short history of general fatigue. Laboratory
      examination of the peripheral blood revealed white blood cells 11,300/microl,
      hemoglobin 10.4 g/dl, platelets 45,000/microl, fibrinogen < 50 mg/dl,
      fibrin/fibrinogen degradation products 536 microg/ml and lactate dehydrogenase
      1,684 U/l. A bone marrow aspirate contained 89.6% of undifferentiated tumor
      cells. A hematological malignancy was suspected and the patient was treated with
      idarubicin and cytarabine. However, further examination revealed that tumor cells
      were positive for CD56 and lacked lineage markers of lymphoid or myeloid cells.
      They were positive for PAS, HHF35 and desmin, and negative for MPO. Reverse
      transcriptase polymerase chain reaction demonstrated PAX3/FKHR fusion
      transcripts, confirming the diagnosis of alveolar rhabdomyosarcoma. Radiological
      examination revealed only one enlarged lymph node being 1.5 cm in diameter at the
      paraaortic region in the abdomen, and failed to find a primary tumor. After three
      courses of chemotherapy containing etoposide, cyclophosphamide, pirarubicin,
      cisplatin and vincristine, tumor cells were eradicated from the bone marrow. The
      patient received an allogeneic bone marrow transplantation eight months after
      diagnosis, although he died of hepatic veno-occlusive disease on day 21. Alveolar
      rhabdomyosarcoma often develops in older children and younger adults, and its
      bone marrow infiltration may mimic acute leukemia.

PMID- 17515124
TI  - [Continuous infusion of coagulant factor concentrates and its pharmacokinetics in
      patients with hemophilics having low titer inhibitor].
AB  - To treat acute episodes of bleeding in patients with hemophilia and low titer
      inhibitor, "neutralization", which is the neutralization of inhibitors using high
      dose coagulant factor infusions, is often selected. However, it is difficult to
      anticipate the dose of continuous infusion (CI) of coagulation products after
      neutralization. We herein present the CI of coagulant products in 2 patients with
      hemophilia and low titer inhibitors and discuss the pharmacokinetics of
      coagulation products. Both patients have had good responses regarding hemostasis
      using CI after the neutralization. The volume of distribution of coagulation
      products in case 2 is 3.7 times and clearances of coagulation products are from 2
      to 3 times as high as those in patients without inhibitors. It is suspected that
      the clearances in patients with an inhibitor are higher than those in patients
      without an inhibitor because a large amount of inhibitor is involved in the extra
      vascular space such as tissue fluid and the reticuloendothelial system. The dose
      for CI of coagulation products after neutralization in patients with inhibitor
      might be better clarified if the reported cases increase and the pharmacokinetics
      are more deeply analyzed.

PMID- 17515126
TI  - [A 2-year-old girl with a generalized scaling of the skin and developmental
      delay].

PMID- 17515125
TI  - [Early relapse of Burkitt's lymphoma with t(8;14) and t(14;18) after rituximab
      combined CODOX-M and IVAC therapy].
AB  - A 43-year-old female was admitted with therapy-resistant pancreatitis and an
      abdominal tumor around the pancreatic head. Laboratory data revealed leukocytosis
      with a white blood cell count of 18200/microl, 25% atypical cells and an LDH of
      13410 IU/l. The bone marrow was comprised of 78.4 percent lymphoblastoid cells
      which were positive for CD10, CD19 and CD20, and the cytogenetic study of which
      demonstrated the presence of t(8;14) (q24;q32) and t(14;18) (q32;q21) in the same
      clone. The patient was diagnosed as having Burkitt's lymphoma (BL) with t(8;14)
      and t(14;18). Although CODOX-M and IVAC therapy combined with rituximab achieved
      complete remission, she died of rapid progressive disease during whole brain
      irradiation before autologous peripheral blood stem cell transplantation. Even if
      the intensive chemotherapy with rituximab is given adequately, durable remission
      may not be achieved in BL with translocation of t(8;14) and t(14;18). A more
      effective therapy remains to be established for the treatment of this disease.

PMID- 17515127
TI  - [Recent advances in epileptology: from molecular biology to clinical aspects.
      Introductory remarks].

PMID- 17515128
TI  - [Na channel gene mutations and epilepsy mouse model].

PMID- 17515129
TI  - [Magnetoencephalography and brain imaging in clinical epileptology].

PMID- 17515130
TI  - [Developmental outcomes of cryptogenic west syndrome: facused on the alteration
      of regional cerebral blood flow during ACTH therapy using SPECT study].

PMID- 17515131
TI  - [Treatment of status epilepticus].

PMID- 17515132
TI  - [Self-assessment of facility-based supports for persons with intellectual
      disabilities and children with motional disabilities].
AB  - To improve the support provided at facilities for persons with intellectual
      disabilities and children with motional disabilities, the author designed a
      questionnaire to be used for self-appraisal by the personnel of the relevant
      facilities. Twenty-one facilities participated; these facilities indicated that
      they needed to improve grievance procedures, the protection of privacy, staff
      training and collaborations with physicians, though they judged themselves to be
      able to respond appropriately to requests from individual users. Facilities for
      children answered that they supplied satisfactory supports, though other
      facilities such as workshops and community homes did not put regulations on
      staffs' abuse in statutory form. Grievance procedures and discussion with users
      are necessary to supply support based on needs of individual users.

PMID- 17515133
TI  - [Features of a short stay service facility for the severely motor and
      intellectually disabled persons in relation to the Niigata Chuetsu Prefecture
      earthquake in 2004].
AB  - Twenty-four handicapped victims of the Niigata-Chuetsu earthquake have used our
      "short-stay-service" . We have summarized the characteristics of this
      utilization. Two prominent patterns were noted:1) The mean duration of the stays
      was clearly longer when compared to ordinary service, and correlated with the
      proximity of the victims to the focus of the earthquake, and 2) victims living
      near the epicenter took longer to start utilizing the short-stay service. The
      Niigata-Chuetsu earthquake has destroyed roads and highways at over 200
      locations, preventing transportation, isolating the seismic center, and resulting
      in delayed rescue of the handicapped victims and their admittance to the
      institution. More of the 24 victims were from the severest region (on 7 of the
      Japanese seismic intensity scale) than from the violent region (scale 6).
      Unfortunately, the social and administrative network for supporting and
      protecting severely motor and intellectually disabled persons is still at an
      embryonic stages. Based of this experience, we propose the building and
      organization of a functional network for the disabled.

PMID- 17515134
TI  - [Hiccup treated by administration of intranasal vinegar].
AB  - A three-year old girl, who had severe cerebral palsy, severe mental retardation,
      and symptomatic epilepsy, was suffering from intractable hiccup that lasted for
      more than an hour since she was 2 years and 10 months old when she undertook
      tracheotomy and laryngotracheal separation. Sometimes this intractable hiccup was
      followed by respiratory arrest. Although the hiccup was resistant to conventional
      medications, the nose drops of small amount of vinegar showed a favorable effect
      on the hiccup. Intranasal vinegar might stimulate dorsal wall of nasopharynx
      where the pharyngeal branch of the glossopharyngeal nerve, which is thought as an
      afferent of the reflex arch of hiccup, is distributed. The administration of
      intranasal vinegar is a safe and handy method to stimulate dorsal wall of
      nasopharynx. We believe that intranasal vinegar administration could be a useful
      nonpharmacologic therapy to cease intractable hiccup.

PMID- 17515135
TI  - [X-linked lissencephaly with absent corpus callosum and abnormal genitalia: a
      report of siblings followed from the prenatal period].
AB  - X-linked lissencephaly with absent corpus callosum and abnormal genitalia (XLAG)
      is caused by a mutation in the ARX gene. We herein report the clinical course of
      siblings with XLAG with a splicing mutation in ARX. Seizures were observed in
      utero. Cerebral atrophy was progressive postnatally, and fetal
      echoencephalography indicated that the atrophy might have started in the prenatal
      period. They had a typical phenotype, except that the genital abnormality of the
      younger brother was not remarkable. A portal-systemic shunt that has not been
      reported in cases with XLAG was seen in the older brother. The siblings had the
      different complications and severity of disease in spite of possessing the same
      mutation.

PMID- 17515136
TI  - [Wernicke encephalopathy in a chronic peritoneal dialysis patient--correlation
      between diffusion MR and pathological findings].
AB  - Wernicke encephalopathy (WE) is a neurologic disorder caused by a nutritional
      deficiency of thiamine. Since the lesion in WE consists of brain edema, diffusion
      weighted imaging (DWI) is quite useful for detecting the pathologic changes in
      WE, and can differentiate between reversible extracellular (vasogenic) and
      irreversible cellular (cytotoxic) edema. We report here a 16-year-old man with WE
      who had been treated with continuous ambulatory peritoneal dialysis for chronic
      renal failure. He underwent repeated DWI and postmortem examination. DWI, which
      was performed 8 days after the onset of neurological symptoms, showed high
      intensity areas in the bilateral thalami, mammillary bodies, tegmentum
      mesencephali and pons. Apparent diffusion coefficient (ADC) map also showed
      slightly high intensity in the periaqueductal gray matter and pons, which
      indicated extracellular edema. On the other hand, ADC map showed low intensity
      areas in the most medial part of the thalami and marginal area of the tegmentum
      mesencephali, which indicated cellular edema. In the postmortem examination, the
      areas that showed low intensity on ADC map exhibited mild neuronal loss. Based on
      the correlation between the DWI and pathologic findings, the cytotoxic edema of
      the bilateral medial thalami and marginal tegmentum mesencephali in this patient
      was considered to be glial cell edema which may protect against neuronal cell
      damage.

PMID- 17515137
TI  - [Clinical characteristics of ulcerative colitis in four patients with severe
      motor and intellectual disabilities].
AB  - We retrospectively reviewed four patients with severe motor and intellectual
      disabilities (SMID), aged 8-56 years, who presented with ulcerative colitis (UC),
      and discussed causal interrelationships between UC and SMID. UC started at 3-50
      years of age with early childhood-onset in two patients. Two patients had an
      intractable clinical course in which leukocytapheresis and surgery were
      ineffective, and resulted in steroid-dependency. We failed to find any causal
      relationships between infectious events, nutrition and anticonvulsants with the
      development of UC. However, when occult blood in feces is frequently positive in
      SMID patients, it is important to consider the possibility of UC and to perform
      an intestinal endoscopic examination.

PMID- 17515138
TI  - [A case of non-herpetic acute limbic encephalitis in childhood--comparison with
      acute encephalitis with refractory repetitive partial seizures (AERRPS)].
AB  - A 9-year-old boy was diagnosed as non-herpetic acute limbic encephalitis (NHALE).
      Four days after the gastrointestinal infection, he developed a generalized
      seizure accompanied with delirium and psychiatric change, which evolved into
      intractable seizures. These seizures were complex partial seizures or generalized
      tonic clonic seizures, and were highly resistant to many anticonvulsants.
      Magnetic resonance imaging of the brain demonstrated reversible symmetrical high
      intensity lesions in the claustra on the diffusion-weighted image. Laboratory
      findings did not suggest herpes simplex virus infection. Further, the clinical
      findings were consistent with those in acute encephalitis with refractory
      repetitive partial seizures (AERRPS). We assume that a part of AERRPS belongs to
      the category of parainfectious limbic encephalitis with repetitive seizures.

PMID- 17515139
TI  - [A severe disabled case of incomplete Fanconi syndrome after discontinuation of
      carnitine supplementation during valproate sodium therapy].

PMID- 17515140
TI  - [Clinical observation of valproate sodium-induced nocturnal enuresis].

PMID- 17515141
TI  - The mirror.

PMID- 17515142
TI  - Entry-to-practice competencies for the registered nurses profession.

PMID- 17515143
TI  - Disclosure and reporting of blood-borne pathogens.

PMID- 17515144
TI  - Should the mayday for nurses appeal be kicked into touch?

PMID- 17515145
TI  - Taking and giving.
AB  - A code of practice sets out how parmaceutical companies can promote medicines to
      health professionals and give information about prescription-only medicines to
      the public.

PMID- 17515146
TI  - The young ones.
AB  - The teenage phenomenon began with the post-war consumer boom and loosening social
      rules. Young people carved out their own identity.

PMID- 17515147
TI  - Sex, drugs and rock 'n' roll.

PMID- 17515148
TI  - Counselling the spirit.
AB  - A 'spiritual director' may be able to help practitioners become more insightful,
      rounded nurses.

PMID- 17515149
TI  - Power of apology.

PMID- 17515150
TI  - Action planning: making change happen in clinical practice.
AB  - This article describes how the authors helped practitioners to develop their
      action planning skills in conjunction with a practice development strategy in an
      acute hospital, using an approach called concept analysis, embellished by a
      systematic literature review. As a result of this, two tools were developed to
      help practitioners become more effective in action planning. This article
      describes the process and the tools that resulted, and illustrates the impact and
      benefits of using these tools in practice. It concludes that action planning,
      when undertaken rigorously and effectively, is a key skill for changing the
      workplace culture from one where the action plan belongs to one person to one
      where everyone takes responsibility for action.

PMID- 17515151
TI  - Voluntary euthanasia: ethical concepts and definitions.
AB  - Euthanasia is a highly emotive and contentious subject, giving rise to a great
      deal of debate. However, despite its frequent exposure in public and professional
      media, there appears to be a lack of clarity about the concepts and definitions
      used in the euthanasia debate. This suggests that discussions on this subject are
      inadequately informed and ineffectual. The ethical focus of the euthanasia debate
      concerns the moral legitimacy of 'voluntary euthanasia'. This article provides an
      overview and clarification of some of the key ethical issues at the centre of
      that debate.

PMID- 17515152
TI  - Appropriate glove use in the prevention of cross-infection.
AB  - This article aims to promote evidence-based practice in glove use and infection
      control. Evidence indicates that improvements in infection control practice can
      reduce the incidence of healthcare-associated infection and exposure to
      communicable disease among healthcare workers. The correct use of gloves is vital
      in the healthcare environment. Gloves should be worn for invasive procedures, any
      contact with sterile sites, non-intact skin, mucous membranes and exposure to
      blood, body fluids and sharp or contaminated instruments. They should be worn
      only once, for one aspect of care and one patient, disposed of as clinical waste,
      and the hands decontaminated after removal.

PMID- 17515153
TI  - Management of antimicrobial-resistant Acinetobacter in hospitals.
AB  - This article examines the management of outbreaks of multi-drug resistant (MDR)
      Acinetobocter in hospitals. It briefly describes the organism and its properties
      and then discusses its role in disease and the risk to hospital patients, routes
      of transmission and patient reservoirs, mechanisms of drug resistance and
      susceptibility to antimicrobial agents, and measures for controlling outbreaks in
      hospitals. The success of these measures is illustrated by a detailed review of
      the control of an outbreak of MDR Acinetobacter boumannii infection in an
      intensive care unit in a London teaching hospital without closure of the ward or
      isolation of the patients.

PMID- 17515154
TI  - First aid for nurses.

PMID- 17515155
TI  - See beyond the illness.

PMID- 17515156
TI  - Case challenges in genetics.

PMID- 17515157
TI  - A 9-year-old boy with labored breathing.

PMID- 17515158
TI  - An 8-year-old girl with hair loss. Trichotillomania.

PMID- 17515159
TI  - A 4-month-old girl with an enlarged tongue and limb asymmetry. Beckwith-Wiedeman
      syndrome.

PMID- 17515160
TI  - A newborn with multiple congenital anomalies. Trisomy 18.

PMID- 17515161
TI  - An 8-year-old girl with short stature. Noonam syndrome.

PMID- 17515162
TI  - Missing fingers and toes. Amnion rupture sequence.

PMID- 17515163
TI  - A 12 year old with scoliosis. Marfan syndrome.

PMID- 17515164
TI  - A 3-day-old infant with a congenital heart defect and hypocalcemia. 22q11
      deletion syndrome.

PMID- 17515165
TI  - Different colored eyes. Waardenburg syndrome.

PMID- 17515166
TI  - A 30 month old with speech delay. Fragile X syndrome.

PMID- 17515167
TI  - An 8-month-old boy with cleft palate, microcephaly, developmental delay, and
      syndactyly. Smith-Lemili-Opitz syndrome.

PMID- 17515168
TI  - A 3 year old with obesity and hypotonia. Prader-Willi syndrome.

PMID- 17515169
TI  - A four-step approach for developing diagnostic tests in psychiatry.
AB  - A four-step approach for developing diagnostic tests in psychiatry is proposed.
      Step 1, a biological variable is observed to be deviant from healthy controls in
      a particular patient population. The demonstration of test retest reliability of
      the finding using blinding procedures is an essential component of this early
      step. Step 2, is the demonstration of potential clinical usefulness of the
      specific finding. The two most important objectives at this step are
      demonstration of difference between the target patient population and appropriate
      control groups (these should be groups of patients with diagnoses that commonly
      appear on the differential diagnostic lists of the target disorder). Estimation
      of the effect size of the finding could be a reasonable guide to which findings
      should be considered good candidates for Step 3 studies. During Step 3 the
      performance characteristics of the test should be established. Specifically, the
      sensitivity, specificity, positive and negative predictive values of the
      biological marker should be examined. Step 4 defines the clinical application of
      the test and helps standardize the technique used in large and multicenter
      clinical trials. Multicenter trials should pave the road towards standardization
      of laboratory procedures used to conduct the test, as well as providing data
      regarding cost effectiveness and impact on both short-term and long-term clinical
      outcomes.

PMID- 17515170
TI  - Challenge tests of monoaminergic systems: neurophysiological aspects.
AB  - Monoaminergic challenge tests allow investigating central nervous changes in
      humans under acute depletion of specific neurotransmitters (5-HT, DA, NE). Along
      with studies using alpha-methyl-para-tyrosine test (AMPT) and
      phenylalanine/tyrosine depletion test (APTD), the tryptophan depletion test
      (ATDT) represents the currently most established human challenge tool for the
      assessment of brain serotonin functioning. Neurophysiological studies in healthy
      and clinical samples may contribute to the search for a non-invasive and reliable
      biological marker of monoaminergic vulnerability or dysfunction. In the design of
      these studies, various biochemical and methodological aspects have to be taken
      into account. This article focuses on electrophysiological methodology and
      results of monoamine depletion studies (i.e., electroencephalography,
      magnetoencephalography, polysomnography, auditory evoked potentials and startle
      response).

PMID- 17515171
TI  - Prediction of clinical response to antidepressants in patients with depression:
      neurophysiology in clinical practice.
AB  - Brain monoaminergic neurotransmission is involved in the pathophysiology of
      various psychiatric disorders including depression. Reliable indicators of
      central monoaminergic activity might be helpful to specifically identify and
      differentiate dysfunctions in individual patients in order to selectively adjust
      medication and predict clinical response. In patients with depression, predictors
      of treatment response to serotonergic versus non-serotonergic (e.g.,
      noradrenergic) antidepressants could be of considerable clinical relevance by
      avoiding unfavorable factors such as a prolonged duration of the disorder, risk
      of suicidality and therapy-resistance. Consequently, these tools might help to
      decrease direct and indirect costs of treatment. The loudness dependence of the
      N1/P2 component of auditory evoked potentials (LD) has been proposed as a
      noninvasive neurophysiological indicator of central serotonergic function. This
      review focuses on recent studies providing evidence for the validity of LD as an
      indirect serotonergic marker and highlights data on the clinical application in
      terms of prediction of treatment response in patients with depression.

PMID- 17515172
TI  - Rostral anterior cingulate cortex activity in the theta band predicts response to
      antidepressive medication.
AB  - During the last 10 years the knowledge about rostral anterior cingulate cortex
      (ACC) activity in major depression has substantially increased. Several groups
      have independently described a relationship between resting activity in this area
      and response to antidepressant treatment. We have recently confirmed a
      relationship between resting activity of rostral ACC activity and response in a
      group of 20 patients with major depression using resting theta activity. In this
      earlier study regions of interest (ROI) were defined in order to establish
      regional specificity. Differences between responders and nonresponders were only
      found in the ACC-ROI, but not in the posterior cingulate region. We have now
      reanalyzed our data using a whole brain voxelwise approach, in order not to miss
      any other relevant functional differences. In addition to major differences
      between responders and nonresponders in the rostral ACC, we have identified a
      nearby region in the midline orbito-frontal region.

PMID- 17515173
TI  - Hand-motor dysfunction in depression: characteristics and pharmacological
      effects.
AB  - Motor retardation is a relevant aspect of depression. Kinematic analysis of
      movements can be applied to explore which type of motor dysfunction is associated
      with depression and to examine motor side effects of antidepressants. Using this
      tool, we aimed to investigate fine motor performance in patients suffering from
      depression and to compare a selective noradrenaline re-uptake inhibitor (NARI)
      (reboxetine) and a selective serotonin reuptake inhibitor (SSRI) (citalopram)
      regarding motor side effects after 4 weeks of treatment. In the first study (I),
      we examined 37 depressed patients and 37 healthy subjects using a digitizing
      graphic tablet and kinematic analysis of handwriting and rapid drawing movements.
      Both groups were comparable regarding age, gender distribution, handedness
      (preponderance of right-handers) and educational level. In the second study (ll),
      we examined different types of hand movements in 16 depressed patients receiving
      citalopram (flexible dosage) and 12 depressed patients treated with reboxetine
      (varying dosage) using the afore-mentioned methods. Both groups were comparable
      regarding age, gender, handedness and the baseline Hamilton Depression Rating
      Scale total score. I: Depressed patients performed drawing with significantly
      less regular velocity than controls (p < 0.001), but normal velocity. Handwriting
      of depressed patients was abnormally slow (p = 0.04). II: Reboxetine led to a
      significant improvement of repetitive drawing movements in depression. In
      contrast, citalopram had no pronounced effects on hand movements in depressed
      patients. I: Irregular patterns of velocity peaks in depressed patients point to
      basal ganglia dysfunction and/or deficient activity of the sensorimotor cortex
      and the supplementary motor area as possible substrates of hand-motor
      disturbances in depression. II: Computer-aided analysis of hand movements is a
      sensitive tool for the registration of differential pharmaceutical effects on
      hand-motor function in depression.

PMID- 17515174
TI  - Influence of anxiety on electrophysiological correlates of response inhibition
      capacities in alcoholism.
AB  - Anxiety disorders are highly prevalent in patients with alcohol use disorder. The
      purpose of the present study was to examine the neural correlates of behavioral
      inhibition in alcohol-dependent patients (ICD-10: F 10.2), and in healthy
      controls and to determine the influence of anxiety on these processes. Therefore,
      behavioral responses (reaction times; error rates) and event-related potentials
      of 16 patients with alcohol dependence syndrome and 16 age-and gender-matched
      healthy controls were recorded while the participants performed an auditory go/no
      go task. The patient group was stratified according to their self-rated trait
      anxiety (STAI) with scores above and below median. We hypothesized that patients
      suffering from alcohol dependence would show reduced no-go P3 amplitudes involved
      in response inhibition compared to healthy subjects. In patients with alcoholism
      and high trait anxiety the decline of no-go P3 amplitudes was expected to be less
      distinct. The estimation of effect size based on the reaction times of patients
      with high and low anxiety ratings revealed a cohen's d of 0.61 indicating a small
      effect. High trait anxiety ratings were also associated with slightly enhanced no
      go P3 amplitudes in central brain regions (Mean no-go P3 amplitude at Cz: 10.43
      microV) compared to patients with low anxiety scores (Mean 8.98 microV). The
      effect size (cohen's d) revealed a small effect. Using the Mann-Whitney-U-test
      for independent samples of the comparison of high- and low-anxious patients,
      however, did not reveal any significant differences concerning no-go P3
      amplitudes. Patients with alcohol use disorder and healthy controls did not
      differ significantly with regard to reaction time, error rate and no-go P3
      amplitudes. This study suggests that no-go P3 amplitudes in patients with alcohol
      use disorder might be affected to some degree by habitual anxiety. The results
      emphasize the importance of monitoring trait anxiety in studies regarding
      cognitive functions in subjects with alcohol use disorder.

PMID- 17515175
TI  - Induced gamma activity and event-related coherence in schizophrenia.
AB  - Evidence has been provided that high frequency oscillations within the gamma band
      reflect mechanisms of cortical integration. In the light of recently proposed
      pathophysiological models of schizophrenia, suggesting a disturbance of the
      functional connectivity within distributed neural networks, it has been
      hypothesized that abnormalities in the gamma band underlie perceptual and
      cognitive dysfunctions in patients with schizophrenia. In the present study we
      investigated evoked and induced 40-Hz gamma power as well as frontoparietal and
      frontotemporal event-related coherence in patients with deficit and nondeficit
      schizophrenia and in matched healthy controls. In patients, correlations between
      gamma oscillations and psychopathological dimensions were also investigated. A
      reduction of both induced gamma power and event-related coherence was observed in
      patients with nondeficit schizophrenia, but not in those with deficit
      schizophrenia. Our findings support the hypothesis that deficit and nondeficit
      schizophrenia represent separate disease entities, suggesting the presence of a
      poor integration of the neuronal activity within distributed neural network only
      in the subgroup of schizophrenic patients without primary and persistent negative
      symptoms. Associations between an excess of gamma oscillations and
      psychopathological dimensions were observed, suggesting that abnormal thoughts,
      behaviors and perceptions might be related to the formation of inappropriate
      neural connections.

PMID- 17515176
TI  - Transcranial and deep brain stimulation approaches as treatment for depression.
AB  - Given that a considerable portion of depressed patients does not respond to or
      remit during pharmacotherapy, there is increasing interest in non-pharmacological
      strategies to treat depressive disorders. Several brain stimulation approaches
      are currently being investigated as novel therapeutic interventions beside
      electroconvulsive therapy (ECT), a prototypic method in this field with proven
      effectiveness. These neurostimulation methods include repetitive transcranial
      magnetic stimulation (rTMS), magnetic seizure therapy (MST), vagus nerve
      stimulation (VNS), deep brain stimulation (DBS) and transcranial direct current
      stimulation (tDCS). It is via different neuroanatomically defined "windows" that
      the various approaches access the neuronal networks showing an altered function
      in depression. Also, the methods vary regarding their degree of invasiveness. One
      or the other method may finally achieve antidepressant effectiveness with
      minimized side effects and constitute a new effective treatment for major
      depression.

PMID- 17515177
TI  - Antiepileptic drugs and mood stability.
AB  - This paper will discuss different definitions of the term "mood stabilizer" and
      highlight in detail the antiepileptic drugs carbamazepine, valproate and
      lamotrigine with respect to their relative strengths in stabilizing mood in
      bipolar patients. These drugs are heterogeneous in their mechanisms of action and
      in their efficacy to stabilize patients with epilepsy and the various mood states
      in bipolar disorder. Lamotrigine has obtained approval in several countries for
      the indication of preventing bipolar depressive episodes, which raises the
      question of differential efficacy of other antiepileptic drugs as mood
      stabilizers in the prevention of either depressive or hypo-/manic episodes. A
      Medline Search to 2006 was conducted for controlled acute and maintenance studies
      of the three scientifically and clinically most established antiepileptic drugs
      carbamazepine, valproate and lamotrigine. The medications discussed in this
      review only partly fulfill definitions of a mood stabilizer, and we suggest that
      future research should focus on combined treatment strategies.

PMID- 17515178
TI  - [Nonspecific clinical signs in pigs and use of exclusion diagnosis for classical
      swine fever: a survey among pig farmers and veterinary practitioners].
AB  - Outbreaks of Classical Swine Fever (CSF) occurred in spring 2006 in Germany close
      to the Dutch border. On 6th April Dutch pig farmers were given the possibility to
      submit blood samples directly via their veterinary practitioner to the National
      Reference Laboratory for CSF if their pigs had non-specific clinical symptoms or
      if pigs were being treated with antibiotics. The pig farm was not quarantined and
      was not visited by the veterinary authorities. Over a period of 9 weeks 156 pig
      farmers submitted whole blood samples via 50 different veterinary practices. All
      samples tested negative in the PCR test. These pig farmers and veterinary
      practitioners were asked to respond to a postal questionnaire with questions
      regarding their experience with this new diagnostic possibility, the distribution
      of the costs involved, a comparison with other instruments, such as official
      notification or use of a leukocyte count test, and their knowledge of clinical
      signs of CSF. 65 pig farmers (42%) and 33 veterinary practices (66%) returned the
      questionnaire. The main results indicated that pig farmers (72%) would use this
      type of exclusion diagnostics sooner than that they would approach the veterinary
      authorities (practitioners: 86%). Moreover the respondents considered the fact
      that the farm was not quarantined immediately to be an advantage (pig farmers,
      79%; practitioners, 88%). 32 percent of the pig farmers were not aware that they
      were required to submit blood samples if pigs were being treated with antibiotics
      (practitioners: 11%). The majority of pig farmers and practitioners were not
      satisfied with the current distribution of the costs involved: in their opinion
      the costs of the PCR test, the costs of the veterinary practitioner and the costs
      for shipping the samples to the reference laboratory should be paid out of the
      Animal Health Fund (50% government and 50% industry) or by the government. If the
      current distribution of the costs is not changed, a large proportion of the pig
      farmers indicated that they would not use this form of exclusion diagnostics for
      CSF in the future. Pig farmers appeared to have a rather limited knowledge of the
      clinical signs of CSF: 33% of the pig farmers could mention maximally three
      clinical signs of CSF, and 7% could not mention a single clinical sign of CSF and
      said they were entirely dependent on the practitioners' ability to judge a CSF
      suspect situation.

PMID- 17515179
TI  - [Part 1. An owner has a sick fish and then?].

PMID- 17515180
TI  - [Hoof and claw health in dairy cows in the Netherlands. Epidemiological aspects
      of hoof and claw diseases in dairy cows in the Netherlands].

PMID- 17515181
TI  - [Non-avoidable complication].

PMID- 17515182
TI  - [The advantage of cost price determination II].

PMID- 17515183
TI  - ["The quality and standards of the veterinary link in the chain of calves meat
      industry].

PMID- 17515184
TI  - Pricing orthopedic implants. "I'll take the mink......".

PMID- 17515185
TI  - Factors associated with thromboprophylaxis for orthopedic patients and their
      impact on outcome.
AB  - We conducted a study to identify the factors affecting inpatient
      thromboprophylaxis use and to assess the impact of pharmacologic prophylaxis on
      the incidence of postsurgical venous thromboembolism (VTE). Our ultimate goal was
      to close the gap in knowledge about the need for thromboprophylaxis, including
      aspirin use. Although prophylaxis was effective in reducing VTE risk in
      orthopedic patients, it seemed to be underused at some hospitals, and use of
      aspirin alone in these patients con-thenumber of hand kneereplacements tinues
      despite guidelines recommending otherwise.

PMID- 17515186
TI  - The glenoid center point: a magnetic resonance imaging study of normal scapular
      anatomy.
AB  - Using 10 normal cadaveric glenoids, Matsen and colleagues described the anatomic
      concept and clinical use of the glenoid centering point during shoulder
      arthroplasty. In the study reported here, we used magnetic resonance imaging
      scans of 50 patients with nonarthritic conditions of the glenohumeral joint to
      evaluate the relationship between the glenoid center line and the scapular neck.
      Results from this larger group of patients confirmed that a reproducible anatomic
      relationship of the glenoid centering line and the centering point on the
      anterior glenoid neck exists and can be used to restore normal anatomy in cases
      of posterior glenoid wear. An understanding of this anatomic relationship vis-a
      vis shoulder arthroplasty may aid in recreating a normal glenoid version.

PMID- 17515187
TI  - Accuracy of injection into the basal joint of the thumb.
AB  - To investigate the accuracy of intra-articular injection of the basal joint and
      to determine the rate of soft-tissue extravasation of injected material in
      successful intra-articular injection, we injected the basal joint of 30 hands
      with radiopaque dye (with fluoroscopy guiding needle placement in 8 cases) and
      then used fluoroscopy to check injection accuracy. Results were recorded
      depending on the location of the injected dye on fluoroscopic examination. Rates
      of intra-articular accuracy and soft-tissue extravasation for successful intra
      articular injections were 100% and 25% for the fluoroscopy-guided group and 81.8%
      and 25% for the "blind" group. This study's accuracy rate for intra-articular
      injection of the basal joint is comparable to the rates reported for injection of
      larger joints. There is a relatively high soft-tissue extravasation rate for
      successful intra-articular injection.

PMID- 17515188
TI  - Osseous healing with a composite of allograft and demineralized bone matrix:
      adverse effects of smoking.
AB  - We report on our use of a composite graft of lyophilized cancellous allogenic
      chips and demineralized bone matrix (DBM; Grafton; Osteotech, Eatontown, NJ) to
      manage traumatic osseous defects and nonunions. Data were prospectively collected
      from all patients who received this composite bone graft between 1996 and 2000.
      Only acute fractures with bone loss resulting in a uncontained defect and
      atrophic non-unions were included in the present study. Demographic data and
      complications related to composite use, tobacco use, and other comorbidities that
      could affect healing were evaluated. One hundred seven patients (112 bone graft
      sites) were followed up for a mean of 32 months (range, 12-60 months). Graft
      sites included the forearm, femur and tibia. Of the 112 patients, there were 56
      smokers (25 non-unions and 31 fractures) and 56 non-smokers (28 fractures and 28
      non-unions). Healing occured in 38/56 smokers compared with 49/56 non-smokers. In
      failed cases, smoking was characteristic in 7/9 non-unions and 11/16 fractures.
      There were 26 acute uncontained injuries, 29 acute contained defects, and 67
      nonunions. Grafting sites were radius/ulna (13 cases), humerus (17), femur (31),
      and tibia/fibula (51). Significant comorbidities were diabetes mellitus (4
      cases), fungal osteomyelitis (1), and pulmonary alveolar proteinosis (1). Eight
      (73%) of the 11 patients with graft failure had a significant smoking history.
      This composite graft is an option for managing osseous defects and nonunions
      traditionally treated with autologous bone grafting but should be used with
      caution when treating patients who are smokers.

PMID- 17515189
TI  - High-pressure water injection causing an isolated tendon laceration: a case
      report.

PMID- 17515190
TI  - Effect of delayed treatment on open tibial shaft fractures.
AB  - Open tibial shaft fractures were analyzed retrospectively to determine the effect
      of treatment timing on infection and nonunion rates. The cases of 77 patients
      with 81 open tibial shaft fractures were reviewed. Patients were treated with
      initial wound cleansing and splinting in the emergency department and then
      formally with operative irrigation and debridement and stabilization, which
      included intramedullary (IM) nailing, external fixation, open reduction and
      internal fixation, or splinting. All tibial shaft components ultimately were
      treated with IM nailing. Mean time to operative treatment was 12.97 hours (SD,
      10.8 hours). There were 7 infections (8.6%) and 3 nonunions (3.7%). Time was
      found not to be a significant factor in predicting either infection or nonunion.
      Increased severity of fracture was a significant factor in predicting infection
      rate. The infection rate for fractures treated first with external fixation and
      then with IM nailing was significantly higher than that for fractures treated
      with IM nailing alone. In addition, a relation was found between patients who
      received multiple debridements and development of infection. These results show
      that infection and nonunion rates were not adversely affected by longer time to
      operative treatment (up to 48 hours) when adequate trauma department open
      fracture care and early initiation of antibiotics were coupled with standardized
      and thorough debridement in the operative theater.

PMID- 17515191
TI  - Kirschner-wire fixation of small bones.
AB  - A simple technique for Kirschner-wire placement in small bones is to place the
      wire over the to-be-pinned bones, push the wire out through the skin, and run the
      wire back across the bones.

PMID- 17515192
TI  - Using photoactivatable fluorescent protein Dendra2 to track protein movement.
AB  - Photoactivatable fluorescent proteins are capable of dramatic changes in
      fluorescent properties in response to specific light irradiation. For example,
      they can be converted from cyan to green, or from green to red, or from
      nonfluorescent to a brightly fluorescent state. Several types of such proteins
      were developed recently, and some of them are already becoming popular tools to
      study protein mobility. Here we provide detailed recommendations on application
      of the monomeric green-to-red photoconvertible fluorescent protein Dendra2 for
      protein tracking in living cultured cells.

PMID- 17515193
TI  - Agar-gelatin for embedding tissues prior to paraffin processing.

PMID- 17515194
TI  - Efficient generation of random chromosome deletions.

PMID- 17515195
TI  - Nonradioactive fluorescence microtiter plate assay monitoring aptamer selections.

PMID- 17515196
TI  - Robust method for distinguishing heterozygous from homozygous transgenic alleles
      by multiplex ligation-dependent probe assay.

PMID- 17515197
TI  - Miniaturized spotter-compatible multicapillary stamping tool for microarray
      printing.

PMID- 17515198
TI  - Determination of silencing potency of synthetic and RNase III-generated siRNA
      using a secreted luciferase assay.
AB  - RNA interference (RNAi) is an established tool for functional genomics studies
      that is also showing great potential for medical applications. Currently, one of
      the main goals in RNAi technology is the design and discovery of potent small
      interfering RNAs (siRNAs). Using a secreted luciferase from Gaussia princeps
      (GLuc), we developed a reporter assay, which allows for rapid potency assessment
      of siRNAs, by measuring luminescence activity in cell culture supernatants. The
      method was applied in microtiter plate format and validated by comparison to
      quantitative reverse transcription PCR (RT-PCR) and Western blot analysis. This
      reporter assay was used to evaluate in HeLa cells the potency of different siRNA
      mixtures generated by RNase III, or several synthetic siRNAs, all directed
      against human p53. The results show that all four siRNA mixtures generated by
      RNase III induce 50%-75% decrease of the reporter activity at less than 10 nM
      transfected concentration. In contrast, only one out of the five commercially
      available synthetic siRNAs showed comparable potency. These results suggest that
      one advantage of using enzymatic complex siRNA mixtures for RNAi is that, unlike
      single synthetic siRNAs, selecting a target region is not important to ensure
      potency.

PMID- 17515199
TI  - Use of a PNA probe to block DNA-mediated PCR product formation in prokaryotic RT
      PCR.
AB  - A novel method eliminating DNA-mediated PCR product formation in reverse
      transcription PCR (RT-PCR) amplification of specific RNA sequences is described.
      The method exploits the higher melting temperature values of peptide nucleic acid
      (PNA)/DNA duplexes compared with DNA/DNA duplexes by binding a sequence-specific
      PNA probe to a genomic sequence immediately overlapping one of the PCR-primer
      attachment sites within the sequence of interest. Hybridization of the blocking
      probe precludes primer attachment to DNA without affecting attachment of the same
      primer to the reverse transcription-generated cDNA sequence. A four-step PCR
      cycle is used that allows the PNA probe to hybridize to the DNA strand at a
      higher temperature just prior to the primer annealing step.

PMID- 17515200
TI  - Assessment of three-dimensional biofilm structure using an optical microscope.
AB  - A method allowing the evaluation of the structure and the calculation of the
      volume of a biofilm, using an optical microscope, is proposed based on the linear
      relation between the intensity of a pixel in biofilm images grabbed on the x-y
      plane and the corresponding number of cells in the z direction, which allows the
      calculation of the biofilm thickness. The method is intended to overcome the need
      for expensive microscopes to study biofilms.

PMID- 17515201
TI  - Specific terminal labeling of DNA molecules.
AB  - We report a simple method to directly label or modify a specific terminus of
      linear DNA molecules. The method is based upon our finding that a presumably
      triple-stranded structure by RecA-mediated formation at the terminus formed with
      deoxyoligonucleotides, whose sequence is complementary to the 5' terminus of one
      of the strands of a double-stranded DNA molecule, is quite stable and can serve
      as a template for DNA polymerase reaction, with the nucleotides being
      incorporated by an exchange reaction. This novel type of nucleotide incorporation
      has made it possible to label a specific terminus of target double-stranded DNA
      molecules by a direct means (without amplification) regardless of its molecular
      size, a procedure previously unavailable. As an application, we show that large
      DNA molecules can be fixed to a solid support in a specific orientation, thus
      being utilized for various analytical purposes of DNA molecules.

PMID- 17515202
TI  - Construction of strong mammalian promoters by random cis-acting element
      elongation.
AB  - Synthetic oligonucleotides containing one of four kinds of cis-acting elements,
      binding sites for activating protein-1 (AP-1), nuclear factor kappaB (NF-kappaB),
      CArG binding factor A (CBF-A), and nuclear factor Y (NF-Y), were randomly ligated
      to construct DNA fragments. These fragments were inserted into the SalI site of a
      promoter probe vector; pGL3-TATASal, which is located immediately upstream of the
      TATA box sequence of the human heme oxygenase 1 gene and linked to the luciferase
      gene to construct 11 plasmid vectors. When these vectors were introduced into PC
      3 cells of human prostate cancer, 6 out of the 11 transfectants showed a
      significantly higher luciferase activity than pGL3-TATASal. The two strongest
      promoters (clone 6 and clone 11) were investigated further Clone 6 turned out to
      be the strongest, showing a 3.0- and 8.4-fold activity in comparison to the two
      frequently used promoters--the cytomegalovirus (CMV) immediate early promoter and
      the simian virus 40 (SV40) early promoter respectively. Clone 11 was less active
      than clone 6, but still showed higher activity than the two promoters. When the
      plasmids were introduced into nine other cell lines, their activities varied but
      were still comparable to the two promoters. These results indicate that the
      method used here is simple and efficient for constructing strong promoters that
      are potentially useful for vectors in either gene therapy or recombinant vaccine.

PMID- 17515203
TI  - Identification of protein interaction antagonists using the repressed
      transactivator two-hybrid system.
AB  - The repressed transactivator (RTA) yeast two-hybrid system was developed to
      enable genetic identification of interactions with transcriptional activator
      proteins. We have devised modifications of this system that enable its use in
      screening for inhibitors of protein interactions from small molecule compound
      libraries. We show that inhibition of protein interactions can be measured by
      monitoring growth in selective medium containing 3-aminotriazole (3-AT) and using
      this assay have identified inhibitors of four independent protein interactions in
      screens with a 23,000 small molecule compound library. Compounds found to inhibit
      one of the tested interactions between FKBP12 and the transforming growth factor
      beta receptor (TGFbeta-R) were validated in vivo and found to inhibit calcineurin
      dependent signaling in T cells. One of these compounds was also found to cause
      elevated basal expression of a TGFbeta-R/SMAD-dependent reporter gene. These
      results demonstrate the capability of the RTA small molecule screening assay for
      discovery of potentially novel therapeutic compounds.

PMID- 17515205
TI  - New CPR guidelines: what you need to know.

PMID- 17515204
TI  - Appreciating the generation gap.

PMID- 17515206
TI  - Influenza vaccination rates for nurses need a boost.

PMID- 17515207
TI  - How to write a test question for the CRNO Certification Exam.

PMID- 17515208
TI  - Laser safety in the operating room.
AB  - Lasers are a safe and effective tool when used appropriately with the proper
      safeguards in place. Institutions that use lasers must have safety protocols in
      place, as well as a Laser Safety Officer overseeing the implementation of these
      protocols.

PMID- 17515209
TI  - Clearer vision: visual freedom through multifocal lenses.

PMID- 17515210
TI  - Great expectations: JCAHO-compliant nursing documentation.

PMID- 17515211
TI  - The judgment operation of ratio production.
AB  - The judgment operation that individuals perform when they set a sensory intensity
      in a predefined ratio to a standard sensory intensity is unknown. The present
      study was conducted to determine this operation by functional measurement.
      Participants first produced a sensory intensity for each combination of various
      predefined ratios and standard sensory intensities. Subsequently, they rated
      these produced intensities. Factorial graphs derived from these ratings were
      essentially parallel. This result shows that participants produced each sensory
      intensity by operating as if they were adding an amount of sensory intensity to
      the respective standard sensory intensity. It was found that this added amount
      varied nonlinearly with the predefined ratio, implying that ratio productions are
      nonlinear.

PMID- 17515212
TI  - Accessory stimuli modulate effects of nonconscious priming.
AB  - In a recent study, it was shown that subliminal priming (SP) effects are affected
      by the temporal predictability of a stimulus onset. If predictability is not
      given, SP effects are eliminated (Naccache, Blandin, & Dehaene, 2002). In two
      experiments, we investigated how different levels of preparation for target
      processing affect SP effects. For this purpose, an accessory tone stimulus was
      presented at different times prior to a subliminal priming task. The results
      demonstrate a clear modulation of the SP effects at different foreperiod
      intervals. Relative to conditions without an accessory stimulus, SP effects were
      smaller for short foreperiod intervals of the accessory stimulus, and larger for
      long foreperiod intervals. The results suggest that the presentation of an
      accessory stimulus facilitates response activation processes because of the
      participants' enhanced level of preparation for stimulus processing.

PMID- 17515213
TI  - Aging and the perception of local surface orientation from optical patterns of
      shading and specular highlights.
AB  - Younger and older observers' ability to perceive local surface orientation from
      optical patterns of shading and specular highlights was investigated in two
      experiments. On each trial, the observers viewed a randomly generated, smoothly
      curved 3-D object and manipulated an adjustable gauge figure until its
      orientation matched that of a specific local region on the object's surface (cf.
      Koenderink, van Doom, & Kappers, 1992). The performance of both age groups was
      facilitated by the presence of binocular disparity (Experiment 1) and object
      rotation in depth (Experiment 2). Observers in both age groups were able to judge
      the surface tilt component of orientation more precisely than the slant
      component. Significant, but modest, effects of age were found in Experiment 1,
      but not in Experiment 2. The ability to perceive local surface orientation
      appears to be relatively well preserved with increasing age, at least through the
      age of 80.

PMID- 17515214
TI  - Closure of salient regions determines search for a collinear target
      configuration.
AB  - Grouping operations offer an effective mechanism by which to structure complex
      visual scenes. Among the various principles that support element integration,
      closure may be regarded as a main factor in shape extraction. In five
      experiments, we investigated the impact of grouping by closure on search for
      target configurations made up of collinearly arranged corner junctions.
      Systematic variations in the configuration of distractor elements were explored
      to investigate how the figural information of distractors interferes with target
      detection. The results showed no search interference for distractor
      configurations that were open forms. By contrast, distractors making up closed
      forms reduced the efficiency of search performance, indicating closure as a major
      contributor to form detection in multielement configurations. In conclusion, the
      effects reported may be considered to arise from mechanisms of unit formation
      that support the rapid extraction of salient regions to guide search.

PMID- 17515215
TI  - Direction-of-motion discrimination is facilitated by visible motion smear.
AB  - Recent evidence indicates that motion smear can provide useful information for
      the detection and discrimination of motion. Further, it has been shown that the
      perception of motion smear depends critically on the density of dots in a random
      dot (RD) stimulus. Therefore, in the present experiments, the contribution of
      perceived motion smear to direction-of-motion discrimination was evaluated using
      RD targets of different densities. Thresholds for direction-of-motion
      discrimination and the extent of perceived motion smear were determined for RD
      stimuli with densities of 1, 2, and 10 dots/deg(2), presented for 200 msec at a
      velocity of 4, 8, or 12 deg/sec. To evaluate the contribution of information
      about orientation from motion smear, thresholds for orientation discrimination
      were measured using parallel lines with the same length as the extent of
      perceived smear. Despite the opportunity for increased summation as RD density
      increases, our results indicate that direction-of-motion discrimination worsens.
      Because perception of motion smear is reduced with an increase in RD density, our
      results are consistent with a facilitation of direction-of-motion discrimination
      by visible motion smear.

PMID- 17515216
TI  - Modeling spatial effects in visual-tactile saccadic reaction time.
AB  - Saccadic reaction time (SRT) to visual targets tends to be shorter when nonvisual
      stimuli are presented in close temporal or spatial proximity, even when subjects
      are instructed to ignore the accessory input. Here, we investigate visual-tactile
      interaction effects on SRT under varying spatial configurations. SRT to bimodal
      stimuli was reduced by up to 30 msec, in comparison with responses to unimodal
      visual targets. In contrast to previous findings, the amount of multisensory
      facilitation did not decrease with increases in the physical distance between the
      target and the nontarget but depended on (1) whether the target and the nontarget
      were presented in the same hemifield (ipsilateral) or in different hemifields
      (contralateral), (2) the eccentricity of the stimuli, and (3) the frequency of
      the vibrotactile nontarget. The time-window-of-integration (TWIN) model for SRT
      (Colonius & Diederich, 2004) is shown to yield an explicit characterization of
      the observed multisensory spatial interaction effects through the removal of the
      peripheral-processing effects of stimulus location and tactile frequency.

PMID- 17515217
TI  - The repetition discrimination task: an objective method for studying perceptual
      grouping.
AB  - Five experiments are reported that demonstrate the use of the repetition
      discrimination task (RDT) to study perceptual grouping effects objectively and
      quantitatively. Experiments 1 and 3 validate the method by measuring grouping
      based on proximity, color similarity, common region, and element connectedness.
      Experiment 2 compares the RDT effects for proximity grouping to explicit
      subjective ratings of grouping strength in identical displays. Experiments 4 and
      5 investigate the effects of size and orientation of surrounding ovals in
      displays in which competing organizations are present. In each case, the RDT
      produces clear, consistent patterns of response times that are consistent with
      predictions based on grouping. It thus represents an objective method for
      studying the full range of grouping phenomena originally described by Wertheimer.

PMID- 17515218
TI  - Cocktail party listening in a dynamic multitalker environment.
AB  - A priori information about the location of the target talker plays a
      critical'role in cocktailparty listening tasks, but little is known about the
      influence of imperfect spatial information in situations in which the listener
      has some knowledge about the location of the target speech but does not know its
      exact location prior to hearing the stimulus. In this study, spatial uncertainty
      was varied by adjusting the probability that the target talker in a multitalker
      stimulus would change locations at the end of each trial. The results show that
      listeners can adapt their strategies according to the statistical properties of a
      dynamic acoustic environment but that this adaptation is a relatively slow
      process that may require dozens of trials to complete.

PMID- 17515219
TI  - Temporal integration of monocular images separated in time: stereopsis,
      stereoacuity, and binocular luster.
AB  - We evaluated stereopsis and binocular luster using electronically controlled
      shutter glasses with alternating monocular stimulation. In Experiment 1, we used
      the standard method for testing stereoacuity to obtain a gradual measure of
      stereopsis. Stereo thresholds decreased with increasing alternating frequency of
      two monocular half-images without a delay between them. Increasing delays led to
      increasing thresholds. In Experiment 2, we compared stereopsis resulting from two
      monocular half-images of a random-dot stereogram and binocular luster with
      respect to the minimum alternating frequency of the two half-images and the
      maximum interocular delay that were tolerated without a breakdown of the
      impression. Below 3 Hz, no stereopsis occurred. Binocular luster was observed
      only above 10 Hz. The mean threshold of interocular delay for detecting the
      global figure in a random-dot stereogram was about 51 msec, but for binocular
      luster it was about 20 msec. Overall, temporal integration was better for
      stereopsis than for binocular luster.

PMID- 17515220
TI  - An efficient technique for revealing visual search strategies with classification
      images.
AB  - We propose a novel variant of the classification image paradigm that allows us to
      rapidly reveal strategies used by observers in visual search tasks. We make use
      of eye tracking, 1/f noise, and a grid-like stimulus ensemble and also introduce
      a new classification taxonomy that distinguishes between foveal and peripheral
      processes. We tested our method for 3 human observers and two simple shapes used
      as search targets. The classification images obtained show the efficacy of the
      proposed method by revealing the features used by the observers in as few as 200
      trials. Using two control experiments, we evaluated the use of naturalistic 1/f
      noise with classification images, in comparison with the more commonly used white
      noise, and compared the performance of our technique with that of an earlier
      approach without a stimulus grid.

PMID- 17515221
TI  - Perception of rhythmic grouping: testing the iambic/trochaic law.
AB  - This study was designed to test the iambic/trochaic law, which claims that
      elements contrasting in duration naturally form rhythmic groupings with final
      prominence, whereas elements contrasting in intensity form groupings with initial
      prominence. It was also designed to evaluate whether the iambic/trochaic law
      describes general auditory biases, or whether rhythmic grouping is speech or
      language specific. In two experiments, listeners were presented with sequences of
      alternating /ga/ syllables or square wave segments that varied in either duration
      or intensity and were asked to indicate whether they heard a trochaic (i.e.,
      strong-weak) or an iambic (i.e., weak-strong) rhythmic pattern. Experiment 1
      provided a validation of the iambic/trochaic law in English-speaking listeners;
      for both speech and nonspeech stimuli, variations in duration resulted in iambic
      grouping, whereas variations in intensity resulted in trochaic grouping. In
      Experiment 2, no significant differences were found between the rhythmic-grouping
      performances of English- and French-speaking listeners. The speech/ nonspeech and
      cross-language parallels suggest that the perception of linguistic rhythm relies
      largely on general auditory mechanisms. The applicability of the iambic/trochaic
      law to speech segmentation is discussed.

PMID- 17515222
TI  - Visual search is guided by prospective and retrospective memory.
AB  - Although there has been some controversy as to whether attention is guided by
      memory during visual search, recent findings have suggested that memory helps to
      prevent attention from needlessly reinspecting examined items. Until now, it has
      been assumed that some form of retrospective memory is responsible for keeping
      track of examined items and preventing revisitations. Alternatively, some form of
      prospective memory, such as strategic scanpath planning, could be responsible for
      guiding attention away from examined items. We used a new technique that allowed
      us to selectively prevent retrospective or prospective memory from contributing
      to search. We demonstrated that both retrospective and prospective memory guide
      attention during visual search.

PMID- 17515223
TI  - The role of attention in the formation of auditory streams.
AB  - There is controversy over whether stream segregation is an attention-dependent
      process. Part of the argument is related to the initial formation of auditory
      streams. It has been suggested that attention is needed only to form the streams,
      but not to maintain them once they have been segregated. The question of whether
      covert attention at the beginning of a to-be-ignored set of sounds will be enough
      to initiate the segregation process remains open. Here, we investigate this
      question by (1) using a methodology that does not require the participant to make
      an overt response to assess how the unattended sounds are organized and (2)
      structuring the test sound sequence to account for the covert attention
      explanation. The results of four experiments provide evidence to support the view
      that attention is not always required for the formation of auditory streams.

PMID- 17515224
TI  - Repair of symptomatic cartilage lesions of the knee: the place of autologous
      chondrocyte implantation.
AB  - An increasing number of patients with cartilage defects of the knee are being
      treated with autologous chondrocyte implantation (ACI). To date, no clear
      guidelines exist for the use and indications of this technique. The BVOT and
      SOBCOT have established a working group to review the clinical results and the
      cost-effectiveness of the various treatment modalities and particularly of ACI.
      This group has formulated recommendations and presents a treatment algorithm
      based on an in-depth review of recent European and American literature, on peer
      reviewed opinions of leading investigators in the field and on a comparative
      analysis of the clinical results and health-economic aspects of current cartilage
      repair techniques.

PMID- 17515225
TI  - Bioabsorbable materials in orthopaedics.
AB  - The applications of bioabsorbable implants in orthopaedic surgery have mainly
      been mandated from the need to eliminate implant removal operations. Although
      they have not gained widespread popularity among orthopaedic surgeons, they still
      represent an area of evolution. Considerable effort has been put into developing
      new bioabsorbable materials with fewer adverse effects. In this article an
      extensive review of the literature is presented emphasising on basic science and
      clinical applications of these materials. A review of the types of implants, the
      materials used, their biochemical properties, their adverse effects and some of
      the potential future applications is presented.

PMID- 17515226
TI  - Plate fixation of clavicle fractures: a comparative study between Reconstruction
      Plate and Dynamic Compression Plate.
AB  - This study aimed at comparing the results of clavicular fracture fixation with AO
      Reconstruction (Recon) plate and Dynamic Compression Plate (DCP). The case notes
      of 39 patients with 40 acute and chronic clavicular fractures were
      retrospectively reviewed. The indications for fixation for acute cases comprised
      open fractures, the presence of sufficient skin tenting to risk skin integrity,
      neurovascular compromise and severe lateral displacement or comminution. Cases of
      symptomatic atrophic non-union after at least 12 months conservative management
      or previous failed 1/3 tubular plate fixation were also included in the study. In
      total 24 fractures were fixed with Recon Plate and 16 with DCP. Mean time to
      union was 4.2 months for the Recon plate group and 5.4 months for the DCP group.
      Eight of the DCP group complained of plate prominence requiring plate removal.
      Recon plates should be used in preference to DCP whenever clavicular fracture
      fixation is indicated.

PMID- 17515227
TI  - The relationship between Hill-Sachs lesion and recurrent anterior shoulder
      dislocation.
AB  - The relationship between the number of shoulder dislocations and the depth and
      percent of head involvement of the Hill-Sachs lesions was investigated in this
      study. Thirty patients with recurrent anterior dislocation of the shoulder were
      divided into three groups according to the numbers of dislocations they had
      presented: Group 1: 1 to 5 dislocations ; Group 2: 6 to 20; Group 3: over 20. The
      mean percentage of head involvement was 11.9% in the first group, 25.4% in the
      second group and 26% in the third group of patients with Hill-Sachs lesions. The
      average depth of the Hill-Sachs lesions was 4.14 mm in the first group, 5.13 mm
      in the second group and 4.38 mm in the third group. Based on these findings, it
      appears that there is a correlation between the number of dislocations and the
      extent and depth of the Hill-Sachs lesions. Surgical treatment should therefore
      be performed as early as possible in patients with recurrent anterior dislocation
      of the shoulder, in order to prevent progression of the Hill-Sachs lesion which
      can become by itself a cause of instability.

PMID- 17515228
TI  - Management of humeral head fractures with a trauma shoulder prosthesis:
      correlation between joint function and healing of the tuberosities.
AB  - This prospective follow-up study investigated the correlation between healing of
      the tuberosities and the functional outcome after arthroplasty with a trauma
      shoulder prosthesis in elderly patients with non-reconstructible humeral head
      fractures. Surgery was performed on 65 patients (66 shoulders) with a mean age of
      74.9 years. A total of 56 patients (57 cases) underwent clinical and radiological
      evaluation after a mean follow-up of 16 months (range: 4 to 62). Mean Constant
      Score was 50 and the age- and gender-corrected value was 73%. The Constant Score
      was significantly higher (62 points, p = 0.015) if the tuberosities healed. Mean
      ASES index was 68 and correlated significantly with the Constant Score (r =
      0.77). Healing of the tuberosities appears to be crucial to achieve good function
      in patients treated with a humeral head prosthesis. For elderly patients, the
      main objectives are to recover the ability to perform activities of daily living,
      to become pain free, and to reach a high level of satisfaction. All these
      criteria were largely achieved by the procedure described in this paper.

PMID- 17515229
TI  - Treatment of chronic static scapholunate dissociation with the modified Brunelli
      technique: preliminary results.
AB  - A series of 10 patients with reducible chronic post-traumatic scapholunate
      dissociation, treated with the modified Brunelli technique, is presented. The
      general outcome was good with a mean DASH score of 12, a range of motion of 69%
      and gripping force of 77% compared with the contralateral side.

PMID- 17515230
TI  - Tumours of the hand presenting as pathological fractures.
AB  - Tumours represent one of the important differential diagnoses that need to be
      considered while investigating fractures of the small bones of the hand, as this
      can sometimes be the sole or the first presenting complaint. We conducted a
      retrospective study of the Scottish Bone Tumour Registry, analysing the records
      of patients with hand tumours which primarily presented as pathological
      fractures. The registry held records of 233 patients with tumours involving the
      bones of the hand, of which 53 (22.7%) had pathological fractures as the first
      presenting complaint. The average age at presentation was 36.9 yrs. The proximal
      phalanx was the most common bone involved (50.9%). The distal phalanx rarely
      developed pathological fractures due to tumours (5.3%). Most of the lesions
      affected the fifth ray (43.9%) Chondroma was the most common tumour seen (43
      patients). Malignant lesions were an infrequent cause of pathological fractures
      (7 chondrosarcomas and 1 Ewing's sarcoma). Tumours are less commonly seen as a
      cause of fractures in the hand with most such fractures initially treated as
      minor injuries with buddy strapping and early mobilisation. A carefully obtained
      history and study of radiographs is essential to diagnose these lesions.

PMID- 17515231
TI  - Reliability of serial bone scintigraphy classification according to Conway in
      Legg-Calve-Perthes disease.
AB  - Serial bone scintigraphy in Legg-Calve-Perthes disease (LCP) has a good early
      prognostic value. So far, no intra- and inter-observer reliability study on this
      classification has been published. Serial technetium scintigraphy of the hips was
      performed in 40 children with LCP disease, and the hips were classified based on
      their scintigraphic patterns according to Conway. Forty hips were classified
      twice by six observers. The two assessments were made in a different order, with
      a minimum time interval of one month. Unweighted kappa coefficients were
      calculated. Only moderate reliability was measured: intra-observer reliability:
      kappa = 0.573 and inter-observer reliability: kappa = 0.525. Serial bone
      scintigraphy in LCP has an inter- and intra-observer reliability that is only
      moderate. The reliability is better than that observed for the radiological
      Catterall classification and head-at-risk factors, but worse than the reliability
      of the radiological Herring classification.

PMID- 17515232
TI  - Periprosthetic femoral fractures around well fixed implants: a simple method of
      fixation using LC-DCP with trochanteric purchase.
AB  - Periprosthetic fractures of the femur are among the most serious complications in
      hip surgery. Various classifications have been suggested. At present the
      Vancouver classification system probably comes closest to the ideal. Most authors
      recommend internal fixation of the fractures in well-fixed implants (Vancouver
      type B1). However as the fixation to the proximal fragment has always been a
      problem, many types of fixation devices have been used. This retrospective study
      was done to evaluate the efficacy of an LC-DCP with trochanteric purchase, in the
      fixation of Vancouver type B1 periprosthetic femoral fractures. Our study
      included 12 patients, 7 male and 5 female with a mean age of 73 years (range: 57
      to 91). One patient died due to complications not related to surgery and in
      another patient the plate was found broken with a loose implant, which was
      revised. All cases were primary arthroplasties. A long broad LC-DCP was used for
      the fixation. Purchase in the proximal fragment was obtained with screws in the
      greater trochanter. Ten fractures united in an average period of 7 months. The
      mean duration of follow-up was 6.5 years. The final results were evaluated using
      the Harris hip score. The mean Harris hip score was 85 with a range of 75 to 94.

PMID- 17515233
TI  - Autologous chondrocyte implantation: a comparison between an open periosteal
      covered and an arthroscopic matrix-guided technique.
AB  - In this prospective study, the authors compared the Carticel method of autologous
      chondrocyte implantation with the Hyalograft C technique. The aim of the study
      was to compare the clinical outcomes of the two methods, to identify any
      complications and to analyse MRI images of the repair process. Seventeen patients
      who had received autologous chondrocyte implantation with the Carticel technique
      and ten treated with Hyalograft C were assessed. A statistically significant
      improvement was observed in both groups at six months (p < 0.001 for Carticel and
      p = 0.002 for Hyalograft C) and at twelve months after surgery (p < 0.001 both
      for Carticel and Hyalograft C), according to HSS (Hospital for Special Surgery)
      and ICRS (International Cartilage Repair Society) scores. There were no
      statistically significant differences between the two groups. MRI images obtained
      one year after surgery revealed the formation of well-integrated tissue similar
      to the surrounding healthy cartilage in most cases, in both Carticel and
      Hyalograft C groups. Six patients treated with Carticel technique were also
      assessed by second-look arthroscopy and histology of biopsies. The newly-formed
      tissue presented structural features similar to normal cartilage in most cases
      (84%). Molecular analysis was performed to assess mRNA levels of the various
      collagen molecules and proliferation and differentiation factors: the results
      showed that the implanted material undergoes progressive remodelling to
      regenerate hyaline cartilage. Both Carticel and Hyalograft C implantation
      techniques seem to lead to comparable short- and medium-term results. Moreover,
      this study confirmed that MRI is a valid tool in the follow-up evaluation of
      autologous chondrocyte implantation.

PMID- 17515234
TI  - Scarf osteotomy in hallux valgus: a review of 72 cases.
AB  - The Scarf osteotomy is now widely used for the correction of hallux valgus. The
      aim of our study was to evaluate the results after Scarf osteotomy considering
      patient's satisfaction as well as the clinical and radiological results. Between
      1996 and 1999, 72 feet underwent a Scarf osteotomy of the first metatarsal and,
      in 11 feet, an additional Akin osteotomy of the proximal phalanx, for the
      correction of hallux valgus (55 patients: 49 female, 6 male; mean age: 52 years).
      The hallux valgus angle improved significantly, from 32 degrees preoperatively to
      18 degrees at follow-up (minimal follow-up: 6 years; mean: 7.5 years). A second
      operation was necessary in two patients because of recurrence of hallux valgus,
      and a fusion of the first metatarsophalangeal joint was performed in two
      patients. At the time of latest follow-up 78% of the patients were satisfied or
      very satisfied with the result. The Scarf osteotomy combined with Akin's closing
      wedge osteotomy is a safe and effective procedure for the treatment of moderate
      hallux valgus deformities.

PMID- 17515235
TI  - Ultrasound guided steroid injection in the treatment of interdigital neuralgia.
AB  - The aim of this study was to assess the clinical effectiveness of ultrasound
      guided injection in the management of Morton's Metatarsalgia. Patients clinically
      diagnosed with interdigital Morton's neuroma were treated with ultrasound guided
      injection of local anaesthetic and steroid. Fifty four patients were available
      for follow-up, and all had detailed telephone questionnaires completed. These
      questionnaires included a pre and post injection symptom score, and Johnson
      Satisfaction score. The results indicate that 69% of patients had ultrasound
      diagnosis of Morton's neuroma and 31% had an ultrasound diagnosis of
      intermetatarsal bursa. Mean follow-up was 11.4 months. Sixty seven percent of the
      patients were satisfied with the results of treatment. At follow-up 63% of
      patients had no limitation in activity levels, and had no need to modify shoe
      wear. Of all patients included in the study, only three have gone on to require
      surgery for ongoing symptoms. Although some studies have suggested that neither
      injection nor imaging have a role in the treatment of Morton's neuroma, this
      study, however, demonstrates that ultrasound guided placement of local
      anaesthetic and steroid in either an intermetatarsal bursa or Morton's neuroma
      gives a good short and medium-term symptom relief and in the majority of cases
      avoids or at least delays the need for surgery.

PMID- 17515236
TI  - Patients' response to facet joint injection.
AB  - The aim of the present study was to assess prospectively patients' response to
      facet joint injection performed for lumbar back pain, and to check if it
      correlates with the response predicted by the Helbig and Lee scoring system.
      Fifty-seven patients who had facet joint injections for mechanical low back pain
      unresponsive to medical treatment, were followed-up. Patients' perception of
      improvement following the procedure was recorded: complete relief, partial
      relief, no change, worse. This response was compared with the response predicted
      by the Helbig and Lee score. Fifty-one patients out of 57 were available for
      follow-up. At the first follow-up visit (after 8 weeks) 27 (53%) of the patients
      claimed relief (complete relief: 15 or 29%, partial relief: 12 or 24%), no
      relief: 23 or 45%, worse: 1 or 2%. Surprisingly, at the second follow-up visit
      (after 6 months) 35 (68%) of the patients reported improvement (complete relief:
      16 or 31%, partial relief: 19 or 37%), no relief: 16 or 31%. Patients with low
      Helbig and Lee scores were as likely to improve as those with high scores: the
      response to the infiltration did not correlate with the predicted response.
      Spontaneous improvement due to the natural history of back pain, may explain the
      late results. It is difficult to predict which patients will benefit from facet
      joint injections.

PMID- 17515237
TI  - Treatment approach in tandem (concurrent) cervical and lumbar spinal stenosis.
AB  - Spondylotic degeneration can manifest as tandem (concurrent) cervical and lumbar
      spinal stenosis. The primary manifestations include neurogenic claudication, gait
      disturbance and a mixture of findings of myelopathy and polyradiculopathy in both
      the upper and lower extremities. The purpose of this retrospective study was to
      report the existence and management of tandem (concurrent) cervical and lumbar
      spinal stenosis. Between 1998 and 2004, 8 patients (6 women and 2 men) were
      diagnosed with tandem spinal stenosis in a series of 230 patients who underwent
      surgery for spinal stenosis (3.4%). Three patients received cervical surgery
      first and 5 patients lumbar surgery first. The Japanese Orthopaedic Association
      Score of all patients improved from an average of 8.1 preoperatively to an
      average of 11.8 points at discharge and maintained an average of 12.7 points at
      final follow-up. Oswestry Disability Score improved from mean 58.1 to 29 at
      discharge and 19.3 at latest follow-up. All the patients had excellent or good
      results and none deteriorated neurologically. Although tandem spinal stenosis
      occurred relatively infrequently, we concluded that its possible presence should
      not be overlooked. The treatment plan must be designed according to the chief
      complaints and symptoms of the patient.

PMID- 17515238
TI  - Adult osteomyelitis: debridement versus debridement plus Osteoset T pellets.
AB  - This long-term retrospective study investigated the value of debridement versus
      debridement and Osteoset T antibiotic-loaded calcium sulphate pellets in the
      treatment of adult chronic osteomyelitis. Sixty-five patients were included in
      the study. The mean follow-up was 75 months (range: 36 to 334). Forty cases were
      treated by debridement, and 25 by debridement and Osteoset T. The healing rates
      were 60% and 80%, respectively; however, the difference was not significant. In a
      subgroup of 39 patients with medullary osteomyelitis and a normal immune system
      (IA according to the Cierny-Mader classification of adult osteomyelitis), 22
      patients were treated with debridement, 17 with debridement and Osteoset T. The
      healing rates were 59% and 94%, respectively (p < 0.05). Twenty-eight patients
      with Staphylococcus aureus osteomyelitis were also studied apart; 13 were treated
      with debridement and 15 with debridement and Osteoset T. The healing rates were
      46% and 80%, respectively. The difference was not significant. The results
      obtained with debridement were less good than with debridement plus Osteoset T,
      but the difference was not significant, except in a single subgroup. Osteoset T
      obviates the need for removal, which is the rule after implantation of gentamycin
      beads. Bony ingrowth is however limited.

PMID- 17515239
TI  - In-vitro MRI detectability of interbody test spacers made of carbon fibre
      reinforced polymers, titanium and titanium-coated carbon fibre-reinforced
      polymers.
AB  - The purpose of this study was to investigate how different materials affect the
      magnetic resonance imaging (MRI) detectability of interbody test spacers (ITS).
      We evaluated the post-implantation MRI scans with T1 TSE sequences for three
      different ITS made of titanium, carbon fibre-reinforced polymers (CFRP) and
      titanium-coated CFRP, respectively. The main target variables were total artefact
      volume (TAV) and median artefact area (MAA). Additionally, implant volume
      (IV)/TAV and cross section (CS)/MAA ratio were determined. The t test and Newman
      Keuls test for multiple comparisons were used for statistical analysis. TAV and
      MAA did not differ significantly between CFRP and titanium-coated CFRP, but were
      approximately twice as high for the titanium ITS (p < 0.001). MRI detectability
      was optimum for CFRP and titanium-coated CFRP, but was limited at the implant
      bone interface of the titanium ITS. The material's susceptibility and the
      implant's dimensions affected MRI artefacting. Based on TAV, the volume of
      titanium surface coating in the ITS studied has no influence on susceptibility in
      MRI scans with T1 TSE sequences.

PMID- 17515240
TI  - Alternative use of a splash screen.

PMID- 17515241
TI  - Arthroscopic resection of a symptomatic snapping subscapular osteochondroma.
AB  - Painful snapping of the scapula may have an anatomical cause but is usually
      idiopathic. Most patients respond well to conservative measures such as
      physiotherapy or non-steroidal anti-inflammatory drugs. Surgery can be performed
      if conservative treatment is unsuccessful. Conservative measures are less likely
      to be successful if a clear anatomical cause can be found. Several surgical
      techniques have been described, ranging from bursectomy to resection of the
      lesion or of part of the scapula. The lesion is usually resected by an open
      technique. Scapulothoracic arthroscopy has previously been shown to be a safe
      procedure with low morbidity in idiopathic cases. A case is described in which
      painful crepitus of the scapula not responding to conservative measures was
      caused by an inferior subscapular osteochondroma. Arthroscopic resection of the
      osteochondroma was performed using a custom, lesion specific, inferior portal.
      This resulted in restoration of a full and painless function of the shoulder
      within two weeks of surgery.

PMID- 17515242
TI  - Post-traumatic incongruent hip in a 12-year-old boy.
AB  - Traumatic hip dislocation is uncommon in the paediatric population. Post
      reduction radiographs often show an incongruent hip because of tissue
      interposition. We report the case of a 12-year-old boy who was transferred to our
      hospital with an incongruent hip after a skiing accident, without a history of
      hip dislocation.

PMID- 17515243
TI  - Osteonecrosis of the femoral head following medullary nailing of the femur in an
      adult.
AB  - The femoral head receives the majority of its blood supply via branches of the
      medial femoral circumflex artery, whose course runs across the piriformis fossa
      and along the superior aspect of the femoral neck. Cadaveric studies have
      demonstrated damage to the medial femoral circumflex artery in cases where the
      piriformis fossa was the entry point for intramedullary nailing. Although well
      recognised in children, osteonecrosis of the femoral head after intramedullary
      nailing has exceptionally been reported in adults. We present a case of
      osteonecrosis of the femoral head post-epiphyseal closure following IM nailing
      for a femoral fracture in a 22-year-old Caucasian adult.

PMID- 17515244
TI  - Late prosthetic joint infection due to Rothia mucilaginosa.
AB  - We report a chronic hip arthroplasty infection with Rothia mucilaginosa, a Gram
      positive germ belonging to the normal flora of the human oral cavity. Successful
      treatment was achieved by a two-stage hip arthroplasty revision and intravenous
      administration of vancomycin. This case report illustrates the potential
      virulence of R. mucilaginosa in patients with a joint prosthesis. We propose to
      routinely perform specific staining and prolonged culturing techniques for
      unusual germs such as Rothia mucilaginosa when the clinical history, physical
      examination or intra-operative findings suggest an implant infection. This paper
      reviews current antibiotic prophylaxis guidelines for infection prevention of
      joint arthroplasties during dental procedures.

PMID- 17515245
TI  - Total hip replacement infected with Mycobacterium tuberculosis. A case report
      with review of literature.
AB  - Mycobacterium Tuberculosis infection of a total joint prosthesis in patients with
      previous pulmonary or osteoarticular tuberculosis is well recorded in literature.
      We describe the case of a 59-year-old woman with tuberculous infection
      complicating a total hip arthroplasty 15 months after surgery for osteoarthritis.
      The patient had no prior history of exposure to tuberculosis and no evidence of
      pulmonary or osteoarticular tuberculosis. She was treated with four-drug
      antituberculous chemotherapy for 12 months with retention of the prosthesis. The
      purpose of this case report and literature review is to highlight to the Western
      Orthopaedic surgeon the importance of keeping in mind a differential diagnosis of
      tuberculosis while dealing with prosthetic joint infections. The infection of a
      joint with Mycobacterium Tuberculosis in patients without previous tuberculosis
      is very uncommon. We have reviewed the surgical and medical management of the
      cases reported in literature.

PMID- 17515246
TI  - Congenital constriction band with pseudoarthrosis of the tibia: a case report and
      literature review.
AB  - A passive constriction phenomenon has been proposed to explain the development of
      congenital pseudoarthrosis of the tibia. We report a case of congenital
      pseudoarthrosis of the tibia in a child with congenital constriction band
      syndrome, successfully treated with soft tissue release (cutaneous and deep)
      only, restoring normal periosteal blood supply and enabling gradual correction of
      the angular osseous deformity and reformation of the intramedullary canal.

PMID- 17515247
TI  - Giant cell reaction of a metatarsal bone: a case report.
AB  - A rare, non-neoplastic lesion involving the 1st metatarsal bone in a 5-year-old
      female is described. Radiographically it presented as a cystic lesion of the
      whole of the metatarsal. Fine needle aspiration cytology showed it to be a benign
      giant cell lesion. The tumour was excised en bloc and the metatarsal replaced by
      a free fibular graft of adequate length. Histopathological examination confirmed
      the diagnosis as giant cell reaction of bone. The lesion is said to arise as a
      local tissue response to bleeding as evidenced by the clustering of giant cells
      in areas of haemorrhage. The entity should be differentiated from aneurismal bone
      cyst, brown tumours of hyperparathyroidism giant cell tumour, chondroblastoma,
      non-ossifying fibroma etc. Treatment usually consists of curettage or excision of
      the involved bone with or without bone grafting. Recurrences are common in
      curetted lesions.

PMID- 17515248
TI  - Congenital posterior atlas defect associated with anterior rachischisis and early
      cervical degenerative disc disease: a case study and review of the literature.
AB  - A rare case of a wide congenital atlas defect is reported. A 25 year-old woman
      was admitted after complaints of radicular pain in the right arm. Radiographs
      incidentally revealed aplasia of the posterior arch of the atlas together with
      anterior rachischisis. A review of the literature is presented and a possible
      association with early disc degeneration is discussed.

PMID- 17515249
TI  - Cold air-provoked respiratory symptoms: the mechanisms and management.
AB  - OBJECTIVES: To describe the mechanisms and management of cold air-provoked
      respiratory symptoms. STUDY DESIGN: A literature review. METHODS: The review
      includes human epidemiological studies, human and animal experimental studies, as
      well as human studies about management of the cold air-provoked respiratory
      symptoms. RESULTS: Cold air is unlikely to be a causal factor initiating
      respiratory diseases but a symptom trigger. In the present review, the airway
      responses beyond these symptoms were divided into three types. The short-term
      responses are those that develop within minutes in response to sudden cooling of
      the airways. Subjects with asthma or rhinitis are especially prone to these
      responses. The long-term responses are those that develop in response to repeated
      and long-standing cooling and drying of the airways, usually in endurance
      athletes. Finally, there are the physiological, reflex-mediated lower-airway
      responses to cooling of the skin or upper airways. CONCLUSIONS: The mechanisms
      beyond cold air-provoked respiratory symptoms vary considerably and mainly depend
      on the individual's susceptibility and the ventilation level during the cold
      exposure. An understanding of these mechanisms is essential for successful
      management of the symptoms.

PMID- 17515250
TI  - National type 2 diabetes prevention programme in Finland: FIN-D2D.
AB  - OBJECTIVES: Current evidence shows that type 2 diabetes (T2D) can be prevented by
      life-style changes and medication. To meet the menacing diabetes epidemic, there
      is an urgent need to translate the scientific evidence regarding prevention of
      T2D into daily clinical practice and public health. In Finland, a national
      programme for the prevention of T2D has been launched. The programme comprises 3
      concurrent strategies for prevention: the population strategy, the high-risk
      strategy and the strategy of early diagnosis and management. The article
      describes the implementation strategy for the prevention programme for T2D.
      METHODS: The implementation project, FIN-D2D, is being conducted in 5 hospital
      districts, covering a population of 1.5 million, during the years 2003-2007. The
      main actors in the FIN-D2D are primary and occupational health care providers.
      RESULTS: The goals of the project are (1) to reduce the incidence and prevalence
      of T2D and prevalence of cardiovascular risk factor levels; (2) to identify
      individuals who are unaware of their T2D; (3) to generate regional and local
      models and programmes for the prevention of T2D; (4) to evaluate the
      effectiveness, feasibility and costs of the programme; and (5) to increase the
      awareness of T2D and its risk factors in the population and to support the
      population strategy of the diabetes prevention programme. The feasibility,
      effectiveness and costs of the programme will be evaluated according to a
      specific evaluation plan. CONCLUSIONS: Current research evidence shows that the
      type 2 diabetes can be effectively prevented in high-risk subjects by life-style
      changes, which include increased physical activity and weight reduction. FIN-D2D
      explores ways to implement these methods on a national level.

PMID- 17515251
TI  - Population based study of health and living conditions in areas with both Sami
      and Norwegian populations--the SAMINOR study.
AB  - OBJECTIVES: The overall aim of the SAMINOR project was to study health and
      diseases in relation to living conditions among the Sami population and to
      compare these with the Norwegian population in the same area. This article
      provides an overview of the background of the study and a description of the
      methods employed for the data collection. We give sample characteristics and
      elaborate on different definitions of ethnicity. STUDY DESIGN: Cross-sectional,
      population-based study, including questionnaires, a clinical examination and
      analyses of blood samples. METHODS: All individuals 30 or 36 to 79 years of age
      who were living in defined municipalities or specified local areas with a known
      Sami population were invited to a cardiovascular screening program. The data were
      collected during 2003-2004. The questionnaires focused on living conditions,
      health, Sami traditions and ethnicity. The eligible population consisted of
      27,987 individuals and 16,865 (60.6%) participated by answering at least one
      questionnaire. Analyses were restricted to the 36 to 79 year-old age group which
      had 16,538 participants. The screening program comprised a blood sample,
      measurements of blood pressure, height, weight, and waist and hip ratio.
      Different definitions of Sami ethnicity were explored. RESULTS: Of the sample,
      35.6% reported Sami background, and 13.2% reported that they, their parents and
      their grandparents had Sami as their domestic language. This stringent definition
      of Sami produced clearer differences between Sami and Norwegians, as shown for
      some measures of socioeconomic status. CONCLUSIONS: The findings that are related
      to more strict definitions of Sami ethnicity have important implications for the
      interpretation of earlier works and for future studies.

PMID- 17515252
TI  - Inuit anthropometry and insulin resistance.
AB  - OBJECTIVES: Due to the increasing prevalence of obesity among Inuit, a study was
      conducted in an Inuit community to evaluate the anthropometric correlates of
      indices of insulin resistance using the homeostasis model assessment index
      (IR(HOMA)) and the insulin sensitivity index (ISI(0,120)). STUDY DESIGN: Data
      were collected as part of a health screening in a Baffin community in Nunavut,
      Canada, among adults 18 years of age and above. METHODS: A total of 52 Inuit
      participated in the health screening of which 46 completed both the fasting and
      the 2-hour blood tests. Insulin sensitivity indices could be calculated on 45
      participants. RESULTS: Results for women indicated that in age-adjusted linear
      regression analyses, body mass index, waist circumference (WC) and percent body
      fat (%BF) predicted IR(HOMA), and ISI(0,120) (p < 0.05). For men, %BF predicted
      IR(HOMA), and WC and %BF predicted ISI0,120 (p < or = 0.05). CONCLUSIONS: The
      present study suggests that increasing rates of obesity among Inuit will have
      health consequences and that anthropometry is a useful tool to indirectly assess
      insulin resistance/sensitivity.

PMID- 17515253
TI  - Helicobacter pylori infection among non-Native educators in Alaska.
AB  - OBJECTIVES: To determine seroprevalence of H. pylori infection in non-Native
      educators residing in urban or rural settings in Alaska, and to determine
      potential risk factors associated with infection in this population. STUDY
      DESIGN: A cross-sectional survey of non-Native educators residing in urban or
      rural settings in Alaska. METHODS: Participants completed a questionnaire
      detailing aspects of residential life; H. pylori antibody status was determined
      by a commercial assay. RESULTS: Of the 203 non-Native participants, 49 (24%) had
      antibody to H. pylori. Univariate analysis demonstrated that the mean age of
      seropositive participants was higher than of seronegatives (48 vs. 42 years,
      respectively, p = .001). In addition, participants who had experienced childhood
      crowding were more likely to test seropositive for H. pylori (p = .058). On
      multivariate analysis, only age > or = 40 was associated with infection. No
      difference in median hemoglobin or ferritin levels were noted among seropositive
      and seronegative participants. There was no increased risk of seropositivity
      among participants who had lived in an Alaska Native village or in a developing
      country for > or = 6 months. CONCLUSIONS: Overall, 24% of non-Native educators
      residing in rural Alaska tested positive by serology for H. pylori. Age > or = 40
      years was associated with infection. Median hemoglobin or ferritin levels did not
      differ significantly among seropositive and seronegative participants.

PMID- 17515254
TI  - A prospective evaluation of 200 upper endoscopies performed in Alaska Native
      persons.
AB  - OBJECTIVES: To characterize the nature and prevalence of disease in Alaska Native
      patients referred for evaluation of upper gastrointestinal signs and symptoms.
      STUDY DESIGN: Cross-sectional. METHODS: Two hundred consecutive Alaska Native
      patients referred to a statewide tertiary center were prospectively evaluated. A
      standardized data collection form documenting EGD findings was utilized. Routine
      biopsies of the antrum and fundus were taken on all patients. Additional tissue
      was obtained from any areas of clinical concern. RESULTS: Among 200 patients who
      underwent EGD during the study period, 130 (65%) tested H. pylori-positive on
      histology. Among 173 patients with histologic evidence of gastritis, 114 (66%)
      tested H. pylori-positive on histology. Chronic gastritis (87%), gastric ulcer
      (GU 12%), duodenal ulcer (DU 3%) and gastric cancer (2%) were the predominant
      findings. The GU:DU ratio was 4:1, the inverse of that reported in the general
      U.S. population. CONCLUSIONS: Alaska Native patients referred for upper endoscopy
      have a high rate of H. pylori infection with predominantly gastric manifestations
      of disease and a GU:DU ratio, which is the inverse of what is typically seen in
      the U.S. and other developed countries. The high prevalence of H. pylori in
      Alaska Native patients resembles prevalence patterns reported from developing
      countries and may be linked to a rate of gastric cancer that is over three times
      that found in the U.S. population at large.

PMID- 17515255
TI  - Caregiver knowledge and attitudes of preschool oral health and early childhood
      caries (ECC).
AB  - OBJECTIVES: Prevention strategies are integral to improving the oral health for
      young Aboriginal children. For such to be effective, it is important to
      understand the social value that parents and caregivers ascribe to primary teeth.
      The purpose of this paper is to report caregiver knowledge and attitudes toward
      preschool oral health and early childhood caries (ECC) from 4 communities in
      Manitoba. STUDY DESIGN: Cross-sectional study, including a retrospective
      interview with caregivers. METHODS: Children and their main caregivers served as
      the sample. Preschoolers underwent a comprehensive dental screening while
      caregivers completed a questionnaire that explored knowledge and attitudes toward
      preschool dental health. Caregiver responses were matched with findings from each
      child's examination. RESULTS: A majority agreed that primary teeth were
      important, that dental disease could lead to health problems and that a first
      dental visit should be made by age 1. Caregivers of children with ECC were more
      likely to believe that caries could not affect a child's health while those who
      believed primary teeth are important had children with significantly less decay.
      CONCLUSIONS: Most caregivers believed that primary teeth are important and
      correctly responded to inquiries about knowledge and attitudes toward oral
      health. Attitudes on the importance of baby teeth and bottle feeding after one
      year of age, the effect of rotten teeth on childhood health and night-time
      nursing emerged as variables most associated with the absence/presence of ECC and
      deft rates. Incorporating such questioning into caries risk assessments may be a
      useful means to determine a child's risk for ECC.

PMID- 17515256
TI  - Pregnancy health and outcome in two cities in the Kola Peninsula, Northwestern
      Russia.
AB  - OBJECTIVES: The aims of the study were to compare the prevalence of selected
      maternal and lifestyle factors as well as the reproductive outcome of working
      women in two cities in Northwestern Russia (Moncegorsk and Apatity), and to
      assess the quality of pregnancy-outcome data obtained in an interview with
      registered information. STUDY DESIGN: A retrospective questionnaire study in an
      interview format. Women (n =1696) from selected workplaces in Apatity and
      Moncegorsk participated (85% of those available). Information was collected about
      past pregnancies, including information about the pregnancy outcome, newborn,
      occupation, health and life-style. RESULTS: The investigated groups had
      experienced 7,254 pregnancies in total, corresponding to 4.3 pregnancies on
      average per woman. In both groups, about one-half of the reported pregnancies
      were terminated, and three-quarters of the women had undergone an induced
      abortion. Spontaneous abortions had been experienced by 23% of the women in the
      Apatity group, which was higher than in the Moniegorsk group (16%). Previous
      spontaneous abortions appear more likely to be disclosed than induced abortions.
      The smoking prevalence was 37% in the Moncegorsk group and 24% in the Apatity
      group. Thirteen percent of all participants had been diagnosed with a pelvic
      inflammatory disease. CONCLUSIONS: Induced abortions were common in Northwestern
      Russia regardless of city of residency, and the majority of the abortions appear
      to have occurred after the women had their attainable or desired number of
      children. The proportion of pregnancies resulting in a spontaneous abortion was
      higher in the investigated group in Apatity than in Moncegorsk, which should be
      investigated further. This study also confirmed that smoking has become more
      widespread among women in the Kola Peninsula, as elsewhere in Russia.

PMID- 17515257
TI  - Endovascular versus open surgical AAA exclusion techniques the importance of
      individual patient selection criteria.
AB  - Abdominal aortic aneurysms (AAA) are managed by two different treatment options,
      i.e. open graft replacement (OGR) as open surgical technique or endovascular
      aneurysm repair (EVAR) as minimally invasive procedure, to avoid fatal rupture.
      The intention of this review was to show how by offering electively either OGR or
      EVAR - adjusted to the patient's individual risk profile--a benefit for the
      individual patient could be obtained and overall mortality rates of elective AAA
      repair could be significantly reduced. A comparative evaluation of both treatment
      regimes is offered, latest literature as well as own research is presented. Our
      own risk adjusted patient selection regime is described as well as its
      statistically significant impact on overall mortality rates in elective AAA
      exclusion. As conclusion, the benefit of offering both EVAR and OGR is the
      capability to select and recommend the optimal AAA management for the individual
      patient with respect to the individual risk profile. The result is a decrease in
      the overall mortality rate while simultaneously the number of treated patients
      increases. Furthermore EVAR offers a treatment option for otherwise incurable
      high risk patients.

PMID- 17515258
TI  - Iatrogenic spinal epidural abscess.
AB  - BACKGROUND: Iatrogenic epidural abscess complicating neuro-axial blockade is
      rare, but carries significant morbidity and mortality if diagnosis is delayed.
      First documented in 1974, this disorder is now well described in the literature,
      and is increasing in incidence. METHODS: A literature review was undertaken using
      Medline, all relevant papers on this rare, but important, complication of spinal
      epidural anesthesia or analgesia were used. RESULTS: Widespread use of neuro
      axial techniques in the peri-operative period such as epidural analgesia has
      probably contributed to improved surgical outcome but has also led to an
      increased incidence of complications. Epidural abscess or epidural catheter
      sepsis has previously been thought to occur rarely but recent publications
      suggest that it may be more frequent. Predisposing factors include old age,
      diabetes mellitus, alcoholism, cancer, and acquired immunodeficiency syndrome.
      The signs and symptoms of epidural abscess may be nonspecific: including back
      pain, sepsis, with varying neurological deficits, which may present late.
      Magnetic resonance imaging (MRI) provides the most accurate definitive diagnosis.
      The treatment of choice in most patients is early neurosurgical decompression and
      antibiotic therapy. The most common causative organism in spinal epidural abscess
      is Staphylococcus aureus. Prompt diagnosis and specific therapy are the most
      important prognostic factors for a successful outcome. CONCLUSION: Iatrogenic
      spinal epidural abscess is a rare but serious complication which should be
      brought to the attention of all surgeons and anesthetists.

PMID- 17515259
TI  - Carotid endarterectomy versus carotid stenting: an updated review of randomized
      trials and subgroup analyses.
AB  - Atherosclerotic disease of the carotid arteries is responsible for a significant
      portion of ischemic strokes. Carotid endarterectomy (CEA) is currently the
      accepted standard of treatment for patients with severe symptomatic carotid
      stenosis. In the past few years, however, carotid angioplasty and stenting (CAS)
      has emerged as a potential alternative endovascular treatment strategy for this
      disorder. In fact, spurred by the positive results of single center studies and
      small, pivotal randomized trials, some even consider CAS as the treatment
      modality of choice, especially in presumably surgical high-risk patients. Yet,
      randomized trials directly comparing CAS with CEA are sparse and have produced
      conflicting results. The aim of this article is to review the current trial data
      on this issue and to define the role of these techniques for the management of
      two important subgroups of patients. An updated meta-analysis of seven randomized
      trials comparing CEA with CAS demonstrates that CAS is associated with a
      significantly increased risk of any stroke or death within 30 days (OR. 1.41, 95%
      CI 1.07-1.87, p < 0.05). Focusing on patients with a symptomatic carotid
      stenosis, there was also a significant difference in the odds of treatment
      related stroke and death between CAS and CEA (OR, 1.41 ; CI 1.05 to 1.88, p <
      0.05). Data on all disabling strokes and deaths within 30 days was available from
      five trials. The odds of disabling stroke or death at 30 days were similar in the
      endovascular and surgical group (OR, 1.33, 95% CI 0.89 to 1.98). Overall, these
      data do not justify a blind enthusiasm for CAS and a widespread use of this
      procedure for the treatment of carotid artery stenosis. On the other hand, a
      closer inspection of the current literature on elderly patients and those with a
      contralateral carotid occlusion clearly indicates that CAS and CEA already now
      have a complementary role. While elderly patients should preferentially be
      treated with CEA, CAS appears to be the treatment of choice in patients with a
      symptomatic carotid artery stenosis and a contralateral carotid occlusion in
      experienced centers.

PMID- 17515260
TI  - From carotid plaque biology to serologic markers of vulnerability to predict the
      risk of cerebrovascular events.
AB  - Stroke is the second cause of mortality in industrialized countries.
      Atherosclerotic plaque rupture with atheromatous debris distal embolization is
      the pathogenetic mechanism responsible for cerebrovascular events due to
      atherosclerotic carotid disease. Plaque composition rather than lesion burden
      seems to be the determinant factor producing rupture and subsequent thrombosis.
      Histologic features of vulnerability are : a large lipid core, a thin fibrous
      cap, and an inflammatory infiltrate rich of monocytes and macrophages. In the
      clinical practice, it is difficult to predict the risk of experiencing a major
      cerebrovascular events especially in asymptomatic patients. New invasive
      techniques such as intravascular ultrasound with termography, optical coherence
      tomography, fotons spectroscopy and elastography have been developed to detect
      atherosclerotic lesion tissue composition. However, such techniques are difficult
      to apply on a large scale basis in primary prevention. On the contrary, new
      serologic biomarkers such as Pregnancy Associated Plasma Protein-A, Lp-PLA2,
      Interleukin-6, Interleukin-12, metalloproteinases, lipoprotein-(a), and plaque
      oxidative products have been recently proposed for screening general and high
      risk population. The present paper will briefly review the current histologic
      characteristics of vulnerable plaque and the new imaging tools proposed for its
      detection, focusing on the most recent serologic biomarkers evaluated in the
      clinical practice to increase our accuracy in predicting not only the plaque but
      moreover the patient at risk for an acute cerebrovascular event.

PMID- 17515261
TI  - Preliminary results of carotid artery stenting in a non-academic hospital.
AB  - INTRODUCTION: A review of our experience with CAS in a non-academic hospital is
      presented. MATERIALS AND METHODS: A consecutive series of 18 CAS-interventions
      between 2003 and 2005 is studied retrospectively. Indication, medical history,
      preoperative carotid imaging, operative technique and results were studied for
      each patient. RESULTS: CAS was used 12 times in men and six (33.3%) times in
      women between 2003 and 2005. Five (27.8%) symptomatic stenoses, 12 (66.6%)
      asymptomatic stenoses and one (5.6%) arterio-venous fistula were treated. One
      permanent postoperative ipsilateral ischaemic neurologic deficit occurred (5.6%).
      The mean duration of hospital stay was 4.9 days (range : 2-9 days). CONCLUSIONS:
      Our study shows that CAS is feasible in non-academic hospital settings, with
      acceptable early results. Participating in larger studies should confirm our
      results.

PMID- 17515262
TI  - Analysis of surgical treatment of patients with carotid artery stenosis
      endarterectomy versus stenting.
AB  - The aim of this paper is to characterize a group of patients with internal
      carotid artery stenosis and to analyze the outcome of internal carotid artery
      stenosis treatment. The outcome of treatment of 230 patients with internal
      carotid artery stenosis hospitalized from 1st January 2004 to 31 August 2006 was
      analyzed. Twenty nine percent of the patients were selected for medical
      treatment, 70.4% received surgical or endovascular treatment (83.3% of all
      invasive procedures were endarterectomies, versus 16.7% stenting). The peri
      procedural stroke-death rate was 4.9% of patients [3.7% after CEA and 11.1% after
      CAS (N.S.)]. Statistical analysis disclosed that endarterectomy was associated
      with a longer in-hospital stay (p < 0.001). IN CONCLUSION: Both surgical methods,
      endarterectomy and stenting are equivalent in safety and present comparable
      clinical outcomes in selected subgroups of patients (classified to the specific
      procedure on the basis of the type of atherosclerotic plaque).

PMID- 17515263
TI  - Embolism to the brain during carotid stenting and surgery.
AB  - The aim of this study was to assess the prevalence and clinical relevance of
      microembolism in one hundred unselected patients submitted to 50 carotid
      endarterectomy (CEA) and 50 carotid stenting (CAS) procedures from January 2005
      to January 2006 for hemodynamic lesions of the carotid bifurcation (> 70%
      stenosis). MATERIAL AND METHODS: High-resolution Colour-Flow Mapping (CFM),
      Transcranial Doppler (TCD), cerebral computed tomography (CT) or magnetic
      resonance (MR) and four psychometric tests (Mini mental state, Beck depression
      inventory, Zung anxiety inventory, SF-12) were carried out in the preoperative
      evaluation in all the patients. In the CEAs loco-regional anesthesia (100%),
      patch angioplasty (84%) and Pruitt- Inahara shunt (4%) were employed; in the CASs
      local anesthesia (100%), three different carotid stents (Precise-Cordis, Acculink
      Guidant and Carotid Wallstent-Boston Scientific) and three temporary distal
      filter protection devices (Angioguard-Cordis, Accunet-Guidant, Filterwire-EZ-
      Boston Scientific), without pre-dilatation, were employed. TCD monitoring was
      used intra-operatively and 12 hours post-operatively to evaluate the presence and
      the number of microembolic events (ME's) and to investigate the efficiency of
      neuroprotective filter devices. The efficacy of the in situ opened filter was
      judged evaluating the decrease of mean blood velocity in ipsilateral middle
      cerebral artery and the reduction rate of microembolic events (number of
      microemboli detected during the entire procedure/number of microemboli detected
      during the filter positioning). Diffusion-weighted magnetic resonance imaging
      (DWI) of the brain was obtained within 24 to 48 hours after the procedures to
      detect new ischemic brain lesions. Psychometric tests were repeated at the
      discharge of the patient and after two months to evaluate cognitive faculties.
      RESULTS: During postoperative period (30 days) and follow-up, no procedure
      related death and three regressive minor strokes occurred : 1 in CEA (2%) and 2
      in CASs (4%) ; a cranial nerve lesion occurred in CEA (2%). TCD monitoring showed
      ME's (a mean of five events) in 37 CEAs (74%) and in 50 CASs (100%) (a mean of 60
      ME's). In five patients submitted to CAS repeated microemboli occurred during one
      hour postoperative TCD control (10%). A 10-30% decrease of mean blood velocity
      basal value was recorded in the ipsilateral middle cerebral artery when the
      filter device was opened. A mean 70% reduction of ME's was obtained with a
      cerebral protection system deployed. Postoperative DWI detected new focal
      ischemic lesions in 24 patients [22 after CAS (44%) (a mean of 5 new ipsi and
      contra-lateral lesions) , and 2 after CEA (4%). Cognitive capability worsened in
      20 patients [18 after CAS (36%) e 2 after CEA (4%)]. CONCLUSIONS: Mortality and
      morbidity rates of patients submitted to CAS are comparable to the results
      obtained by CEA. A great number of ME's are recorded by TCD during endovascular
      procedures, more than during open surgery. ME's due to CAS are reduced by filter
      protection devices, but the cognitive faculties in a great number of
      "asymptomatic" patients are decreased after CAS.

PMID- 17515264
TI  - Does a foamy-block mattress system prevent pressure sores ? A prospective
      randomised clinical trial in 1729 patients.
AB  - BACKGROUND: Pressure ulcers are a frequent complication of bed rest. The
      development of an efficient and low cost pressure relieving system for the
      prevention of bed-sores would be of considerable hospital health and economic
      interest. Our study was designed to determine the effectiveness in pressure-sore
      prevention of an interface pressure-decreasing mattress, the Kliniplot mattress,
      used in our institution since 1978. METHODS: In a prospective randomised
      controlled 7-month clinical trial we compared the Kliniplot mattress with our
      standard hospital mattress in 1729 patients admitted to medical and surgical
      departments (neurology, cardiology, oncology-haematology, neurosurgery, thoracic
      surgery and orthopaedic surgery). Two groups (Klinipot mattress and standard
      hospital mattress) were monitored for the prevention of pressure sores. The
      patients were evaluated on a daily basis from their admission until the eventual
      occurrence of a bed-sore. Patients' characteristics and pressure-sore risk
      factors were similar at the baseline in both groups. Patients presenting with a
      pressure sore at the time of admission were excluded. RESULTS: Forty-two of the
      1729 patients (2.4%) who entered the study developed at least one pressure sore.
      Twenty-one of the 657 patients (3.2%) nursed on the Kliniplot mattress, and 21 of
      the 1072 patients (1.9%) on the standard mattress developed bed-sores (p =
      0.154). The median time for the occurrence of pressure sores was 31 days (range 6
      87) with the Kliniplot mattress and 18 days (range 2 to 38) with the standard
      mattress (p < 0.001). The risk categories for developing bed-sores using the
      modified Ek's scale were no different at the baseline between both groups (p =
      0.764). The severity of the pressure sores was no different between both groups
      (p = 0.918). CONCLUSIONS: Our results show that the occurrence of pressure sores
      is not reduced but is delayed when patients are nursed on a Kliniplot pressure
      decreasing mattress.

PMID- 17515265
TI  - 'Use of electrothermal vessel sealing with LigaSure device during laparoscopic
      splenectomy'.
AB  - PURPOSE: Main causes of conversion to open surgery are uncontrolled bleeding from
      splenic hilum and capsular injury of spleen during laparoscopic splenectomy (LS).
      We present the use of LigaSure in laparoscopic splenectomy for hemostasis.
      MATERIAL & METHOD: Between January 2005 and May 2006, LS was performed in a total
      of 29 patients (6 male and 23 female) with a mean age of 35.44 +/- 13.63.
      Indications for splenectomy were idiopathic thrombocytopenic purpura (ITP) in 20
      patients, thrombotic thrombocytopenic purpura (TTP) in 2, hereditary
      spherocytosis (HS) in 3, lymphangioma in 2, hodgkin lymphoma in 1 and splenic
      cyst in one patient. LS was performed in the right semilateral position with
      three 10 mm trocars. LigaSure was used in dissection and division of splenic
      ligaments and hilar vascular structures. RESULTS: Conversion to open surgery was
      necessary in one patient due to peroperative bleeding. The mean duration of the
      operation was 71.3 +/- 19.8 minutes and the estimated blood loss was 85 +/- 23
      ml. The diameter and the weight of the spleen were 10.7 +/- 2.68 cm and 250 +/-
      90 g, respectively. There was no mortality. Postoperative complications included
      pancreatic fistula, trocar site infection and deep venous thrombosis that were
      encountered in three patients. These were managed without morbidity. The overall
      complication rate was 10.3% (n = 3). The mean duration of postoperative hospital
      stay was 2.86 +/- 1.59 days. CONCLUSION: LigaSureTM use in LS had easy
      application, provided sufficient hemostasis, and shortened the operative time.

PMID- 17515266
TI  - Varicose veins in ambulatory surgery : patients' perception.
AB  - INTRODUCTION: It is mandatory to perform venous surgery in ambulatory surgery
      units. The aim of this study is to analyse the patient's perception concerning
      the period before hospital discharge. STUDY DESIGN: This was a prospective
      observational study of 100 patients who underwent primary varicose vein surgery.
      Venous disease was assessed according to the CEAP classification and VCSS system.
      The perception of anxiety or psychological apprehension was documented by simple
      questions. Additionally, we recorded the daily postoperative pain, the return to
      normal activity and the patient's satisfaction score. RESULTS: Four patients
      required unplanned admission from the ambulatory surgery floor to the hospital
      unit: two for medical reasons (urinary retention and haematomas) and two ladies
      who stayed overnight because of a severe anxious state. When questioned about the
      potential anxiety before hospital discharge, the majority of patients (87%)
      declared no psychological apprehension. Eleven patients decided to leave the
      hospital despite potential distress. Patients with distress were more frequently
      male (p = .75) with superficial phlebitis (p = .49), pre-operative painful
      varicose veins (p = .13) and a higher number of surgical incisions (p = .35). The
      only significant difference existing between patients with or without anxiety was
      regarding the complication rate in the recovery room (p = .04). CONCLUSION:
      Despite careful patient selection, psychological distress could not be prevented
      or predicted. There is no doubt however that taking these emotional factors into
      consideration in outpatient surgical practice is essential.

PMID- 17515267
TI  - Hybrid repair of aortic arch aneurysm.
AB  - BACKGROUND: Conventional surgical repair of the aortic arch using cardiopulmonary
      bypass and deep hypothermic circulatory arrest still carries a substantial rate
      of mortality and morbidity especially myocardial injury, and predicts a high
      incidence of permanent neurological injury. Endovascular stent-graft placement
      has been developed as an effective treatment modality in various diseases of the
      descending aorta. Technological improvements nowadays allow deployment in the
      distal arch in most instances. However, in case of total involvement of the
      aortic arch endovascular SG repair, the challenge is to maintain blood flow to
      the brain and upper extremities, that may require covering one or more aortic
      branches in order to establish a secure proximal landing zone, and to ensure
      complete exclusion of the lesion. The aim of this study is to report our ongoing
      experience with endovascular treatment of aortic arch aneurysms. METHODS: During
      two years, 16 patients were treated with thoracic stent-grafts, after aortic arch
      debranching for repair of aortic arch aneurysm. All patients were at high risk
      for open repair and not candidates for standard endovascular repair due to
      inadequate proximal landing zones. Device design and implant strategy were on the
      basis of evaluation of aortic morphology with spiral CT. Stent grafts were
      inserted to repair the arch after supra-aortic vessel transposition was
      performed. Follow-up was 100% complete (mean 18 +/- 2.5 months, range 12-24
      months). Follow-up included clinical examination, chest X-ray and computed
      tomography at discharge, 6 months after stent-graft placement and yearly
      thereafter. RESULTS: Primary technical success rate was 100%. Patency of all
      endografts and conventional bypasses was 100%. No endoleak or graft migration was
      observed. There were no neurological complications. Surgical conversion was never
      required. CONCLUSION: Hybrid aortic arch repair is technically challenging but
      feasible. This novel approach may be an alternative to standard open procedures
      in high-risk patients and emergency cases. However, the promising early results
      need to be confirmed by longer follow-up and larger series.

PMID- 17515268
TI  - Percutaneous viabahn-assisted subintimal recanalization (VASIR) for severe
      femoropopliteal occlusive disease.

PMID- 17515269
TI  - Empyema in adults and children: difference in surgical approaches, report of 139
      cases.
AB  - AIM: We investigated specific aetiology and different therapeutic approaches in
      patients with empyema in a General Thoracic Surgery Clinic. MATERIAL AND METHODS:
      Charts of 139 patients admitted with empyema, between January 1998 and March 2005
      were retrospectively reviewed. Although not completely comparable, patients were
      divided into two groups; Paediatric (n = 71) and adult (n = 68) cases. In
      addition to demographic characteristics, treatment options, complications and
      clinical outcomes were investigated according to the specific group. RESULTS: The
      mean age was 5.6 years (4 mo - 17 y) for paediatric patients and 49.6 years (20
      81 y) for adult patients. Overall, 65% of the patients (n = 91) were male. All
      paediatric cases had parapneumonic empyema, while 63% of the adult cases had
      parapneumonic and 23.5% had postoperative empyema. Of the paediatric cases, 50%
      received fibrinolytic treatment in addition to tube thoracostomy and 35% had
      decortication. In adults, 42% had tube thoracostomy and fibrinolytic treatment,
      and decortication was required in 9% only. Thoracomyoplasty was performed in 12%
      of the patients (n = 8). We had no mortality in paediatric patients, however
      mortality rate was 8% in the adult group. Morbidity, consisted mostly of
      prolonged air leakage and impaired lung expansion. CONCLUSION: Early
      decortication and fibrinolytic treatment are sufficient for paediatric patients,
      while a variety of techniques including open drainage, rib resection and
      thoracomyoplasty are required in adult patients with empyema.

PMID- 17515270
TI  - The prophylactic effect of L-arginine in acute ischaemic colitis in a rat model
      of ischaemia/reperfusion injury.
AB  - BACKGROUND/AIMS: The decreased synthesis of nitric oxide (NO) during
      ischaemia/reperfusion (I/R) has been implicated as the major underlying mechanism
      for the pathogenesis of acute ischaemic colitis (A.I.C.). The aim of this study
      was to investigate the prophylactic effect of L-arginine, a NO donor, on tissue
      injury during intestinal I/R, and compare its efficacy with that of exogenous
      vasodilators (molsidomine) and inert nitrogen-containing molecules (casein).
      MATERIAL AND METHODS: One hundred forty four Wistar rats underwent occlusion of
      the superior mesentery artery for 30, 60 and 90 min for induction of intestinal
      ischaemia, followed by 90 min of reperfusion. The rats were randomly assigned to
      receive L-arginine, molsidomine, or casein hydrolysate. In all groups, apart of
      the histological study, we determined the levels of serum malondialdehyde (MDA),
      a reliable marker indicating the degree of the tissue damage after intestinal
      I/R. RESULTS: Serum MDA levels were significantly lower in the L-arginine group
      compared to the untreated animals or those that had received molsidomine or
      casein, after a period of ischaemia of 90 minutes (p < 0.0005), as well as after
      a period of ischaemia of 60 or 90 minutes followed by a 90 minutes reperfusion (p
      = 0.011, and p < 0.0005, respectively). In addition, lesser histopathological
      damage was noted after the use of L-arginine compared to that caused by the
      administration of molsidomine and casein. CONCLUSION: These findings support a
      prophylactic effect of L-arginine in experimentally induced intestinal ischaemia.
      In short, L-arginine attenuates the degree of tissue damage in intestinal
      ischaemia and promotes healing of intestinal mucosa.

PMID- 17515271
TI  - Bilateral lobar lung transplantation--the first two cases in Belgium.
AB  - In the last twenty years lung transplantation has become an established treatment
      for end-stage lung failure refractory to medical management. Over this time,
      better short and long-term results have been achieved due to improvements in
      organ procurement, perfusion and preservation strategies, newer immunosuppressant
      regimes and better post-transplant care. The limiting factor for the number of
      lung transplantation procedures performed is the shortage of available donor
      organs. This results in longer waiting times for listed patients, with a
      substantially increased risk of dying prior to transplantation, especially in the
      paediatric population. Several surgical strategies have evolved to overcome the
      donor shortage, with lobar transplantation becoming a viable alternative. We
      describe our initial experience with two young patients with end-stage cystic
      fibrosis (CF) who required lung transplantation. Given their small size it was
      not possible to transplant an entire lung from an adult donor in each hemithorax.
      We describe lobar transplantation as a technique used to overcome this, in the
      first such operation in Belgium.

PMID- 17515272
TI  - Fluorescence diagnosis of face-located basal cell carcinomas: a new
      dermatological procedure which may help the surgeon.
AB  - Cutaneous Fluorescence Diagnosis (FD) is a new promising dermatological procedure
      which is based on the combination of a local application of a photosensitizer
      such as 5-aminolevulinic acid (ALA) or its methyl ester (MAL) and the use of a
      light source (red light) adapted to the absorption spectrum of these molecules.
      The targeted photosensitization of skin cancers, particularily superficial and
      extensive lesions including superficial basal cell carcinoma and Bowen's disease,
      by ALA or MAL induced porphyrins leads to a selective red fluorescence which can
      be demonstrated by Wood's lamp. This technique may be useful either to define
      better the choice of margins or to detect earlier and or multifocal recurrences.

PMID- 17515273
TI  - A case of a spontaneous popliteal arteriovenous fistula.
AB  - This case report describes a 69-year-old female diagnosed with a spontaneous
      popliteal arteriovenous fistula of the right leg. Some deliberation is given on
      the aetiology of this rare condition as well as a description of the diagnostic
      and therapeutic options for fistula of the popliteal artery in general.

PMID- 17515274
TI  - Hybrid repair of type B dissecting aneurysm with associated Kommerell's
      diverticulum.
AB  - Endovascular therapy has revolutionised vascular surgery. Complex open surgical
      procedures may be replaced with a combination of extra-anatomical reconstruction
      and endovascular treatment. This minimally invasive approach is associated with a
      lower peri-operative morbidity and mortality than open repair. We describe a
      novel 2-stage treatment in a patient with Type B thoracic aortic dissection with
      subsequent aneurysmal dilatation and the added difficulty of a concomitant
      aneurysmal aberrant right subclavian artery (Kommerell's diverticulum).

PMID- 17515275
TI  - Infections and immunosuppression as specific problems in a HIV + patient
      transplanted for end-stage alcoholic cirrhosis.
AB  - We report the case of a 54-year old man with decompensated alcoholic liver
      cirrhosis and HIV infection who underwent liver transplantation (LT). Due to
      relatively well preserved cellular immunity until 2003, no antiretroviral therapy
      (HAART) needed to be instituted. However, deterioration of his clinical state
      indicated LT. At that time, the viral load was of 4.84 Log and the CD4 count was
      more than 250 cells/mm(3). The posttransplant course was complicated by several
      infection episodes and one episode of acute cellular rejection grade 2. HAART
      consisted of Lamivudine, Stavudine, Lopinavir and Ritonavir. One week after
      beginning of HAART, tacrolimus was discontinued during 18 days due Ritonavir
      interaction. CD3/CD4 T-helper lymphocyte count showed a significant decrease
      immediately after LT which rapidly recovered after initiation of HAART. The
      patient was discharged on the 8th postoperative week in good conditions. This
      report encourages the institution of HAART once the liver graft regains normal
      function. Drug interactions between Ritonavir and Tacrolimus should be
      anticipated. A study protocol to manage these patients within a multidisciplinary
      team including also specialists in infectious diseases and virologists is
      mandatory.

PMID- 17515276
TI  - Bilateral adrenal lymphoma with Addison's disease : a surgical pitfall.
AB  - A 65 year old man presenting with abdominal and back pain was found to have
      bilateral adrenal masses. Phaeochromocytomas were initially suspected on the
      basis of increased catecholamine excretion. This diagnosis seemed unlikely in
      view of clinical findings and a negative 123I-metaiodobenzylguanidine
      scintigraphy. A biopsy of the right adrenal mass revealed a diagnosis of primary
      adrenal B-cell lymphoma. Hyponatraemia and subtle clinical signs of adrenal
      insufficiency led to a diagnosis of Addison's disease, a common complication of
      primary adrenal lymphoma. Thus, bilateral adrenal masses associated with
      Addison's disease should raise the suspicion of possible primary adrenal
      lymphoma.

PMID- 17515277
TI  - Perforation and abscess formation of a solitary jejunal diverticulum.
AB  - Perforation of a jejunal diverticulum is a rare clinical entity. Its elusive
      clinical presentation often delays diagnosis resulting in high morbidity and
      mortality rates. We report a case where a female patient was treated
      conservatively for an intra-abdominal abscess of unknown origin. After three
      weeks, an exploratory laparoscopy was performed. The definitive diagnosis was an
      abscess resulting from a perforated solitary jejunal diverticulum.

PMID- 17515278
TI  - Early decortication in childhood empyema thoracis.
AB  - Thoracic empyema is a life-threatening condition in paediatric surgical practice
      and the appropriate management still remains controversial. The authors reviewed
      79 (37 boys, 42 girls) cases of empyema thoracis who underwent thoracotomy and
      decortication between 1990 and 2005. The initial diagnosis based on history,
      physical examination and radiology was confirmed by thoracentesis. Fever, cough
      and dyspnoea were the most common presenting symptoms. In all cases aerobic
      cultures were performed and Staphylococcus aureus was the most common
      microorganism isolated. All patients except three received antibiotics and tube
      drainage as an initial treatment. The decision for early decortication was based
      on persistence of fever, dyspnoea, air leakage and lack of resolution on CT scan,
      in spite of medical therapy and tube drainage, at the end of 10 days. All but one
      with wound dehiscence showed rapid recovery and they were discharged on the fifth
      to eighth postoperative days. In conclusion, early decortication is a safe and
      curative treatment in childhood empyema thoracis with low morbidity.

PMID- 17515279
TI  - Climbing up the medical ladder : the surgeon-accoucheur Jan Bernard Jacobs (1734
      1790).

PMID- 17515280
TI  - Is it better to be a nurse in Scotland?

PMID- 17515281
TI  - 'It is fair to assume a link between back injury in nurses and patient obesity'.

PMID- 17515282
TI  - Halting death by indifference.

PMID- 17515284
TI  - Ensuring patient dignity when accessing and using toilets.

PMID- 17515283
TI  - The goal of better nurse pay.

PMID- 17515285
TI  - The removal of sutures.

PMID- 17515286
TI  - Chronic obstructive pulmonary disease. Part one--diagnosis.
AB  - This two-part series covers diagnosis and management of COPD. The first part
      focuses on presenting symptoms, methods of diagnosis and differential diagnoses.
      Part two (next week) covers non-drug and pharmacological management of the
      condition.

PMID- 17515287
TI  - 'This government is failing its key workers'.

PMID- 17515288
TI  - Anti-atherosclerotic effect of cilostazol in apolipoprotein-E knockout mice.
AB  - To investigate whether cilostazol (CAS 73963-72-1), a selective phosphodiesterase
      3 inhibitor, reduces the progression of atherogenic diet-induced atherosclerosis,
      cilostazol was orally administered twice a day for 4 weeks to male apolipoprotein
      E knockout (ApoE KO) mice. In serial sections of the aortic root, the
      atherosclerotic lesion ratios in the cilostazol-treated groups (32.5 +/- 3.3% for
      100 mg/kg, 29.0 +/- 2.9% for 300 mg/kg) were significantly and dose-dependently
      smaller than that of the control group (40.2 +/- 3.7%). Cilostazol also
      significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM
      1) and monocyte/macrophage accumulation in the aortic root and increased high
      density lipoprotein(HDL) cholesterol levels in plasma. These results suggest that
      cilostazol suppresses the progression of atherosclerosis in ApoE KO mice by
      inhibiting adhesionand infiltration of monocytes and reducing cholesterol
      accumulation in atherosclerotic lesion.

PMID- 17515289
TI  - Bioequivalence study of two metformin formulations.
AB  - A randomized single-dose cross-over study was conducted on 24 healthy male
      volunteers to compare the bioavailability of two metformin (CAS 657-24-9) tablet
      formulations, Emiphage (test) and a commercially available original preparation
      (reference). A dose of 850 mg was administered after an overnight fast with a
      washout period of seven days. Eighteen blood samples were collected over 32 h.
      Metformin concentrations in deproteinized serum were determined by a locally
      validated High Performance Liquid Chromatographic (HPLC) assay, and
      pharmacokinetic parameters were analyzed by the standard non-compartmental
      method. Mean +/- SD maximum concentration (C(max)), time to reach maximum
      concentration (T(max)), area under the curve (AUC(0 --> t) and AUC(0 -->
      infinity)), and elimination half-life (t(1/2)) were 1.73 +/- 0.54 and 1.86 +/-
      0.67 microg/ml, 2.6 +/- 1.2 and 2.0 +/- 1.0 h, 10.72 +/- 3.93 and 10.82 +/- 3.72
      microg x h/ml, 11.53 - 4.14 and 11.6 +/- 3.84 microg x h/ml, and 3.1 +/- 0.7 and
      3.1 +/- 0.9 h for the test and reference formulation, respectively. The
      parametric 90% confidence intervals on the mean of the difference (test -
      reference) between log-transformed values of the two formulations were 82.92% to
      98.78%, 85.95% to 101.47%, and 77.82% to 100.4% for AUC(0 --> t), AUC(0 -->
      infinity), and C(max), respectively. The results indicate that the two
      formulations can be considered equivalent in the extent of absorption under
      fasting conditions.

PMID- 17515290
TI  - Design and synthesis of some new thiazolo [3,2-b]-1,2,4-triazole-5(6H)-ones
      substituted with flurbiprofen as anti-inflammatory and analgesic agents.
AB  - In the course of our ongoing studies, a series of thiazolo[3,2-b]-1,2,4-triazole
      5(6H)-ones substituted with flurbiprofen (CAS 5104-49-4) has been prepared. The
      compounds were synthesized by the cyclization of the 3-[(2-fluoro-4
      biphenyl)ethyl]-5-mercapto-1,2,4-triazole (3) with chloroacetic acid and relevant
      benzaldehydes in the presence of acetic acid, acetic anhydride and anhydrous
      sodium acetate in one step. The product of this one-pot synthesis that
      precipitated on cooling of the reaction mixture was identified undoubtedly by X
      ray crystallographic analysis as thiazolo[3,2-b]-1,2,4-triazole. In-vivo anti
      inflammatory and analgesic activities of the compounds were assessed by
      carrageenan-induced hind paw edema and p-benzoquinone-induced abdominal
      constriction tests in mice, respectively. In addition, the ulcerogenic risks were
      evaluated. It is worthy of saying that the compounds which maintained
      analgesic/antiinflammatory activity of the starting compound were found to be
      safer with regard to gastric lesion risks at 100 mg/kg oral dose when compared
      with flurbiprofen. Among the synthesized compounds 3d showed the highest
      analgesic and antiinflammatory activity without inducing any gastric lesion and
      deserves further attention in order to develop new lead drug candidates.

PMID- 17515291
TI  - [Therapy of osteoarthritis crystalline glucosamine sulphate/a review of the
      clinical effcacy].
AB  - The pharmacological treatment of osteoarthritis is traditionally accomplished
      with nonspecific symptomatic agents, which are generally effective only for acute
      symptom relief. Compounds are under investigation that might exert specific
      effects on osteoarthritis pathogenesis and thus induce at least a similar short
      term symptomatic effect, but also control disease progression in the long term.
      Glucosamine sulphate (CAS 29031-19-4) reverses the proinflammatory and joint
      degenerating effects of interleukin-1 by inhibiting the cytokine intracellular
      pathway. Clinical trials with the crystalline glucosamine sulphate formulation
      (CGS; dona) approved as a medicinal drug, predominantly used at the oral dose of
      1,500 mg once daily, demonstrated a specific symptom-modifying effect on knee
      osteoarthritis over short- and long-term treatment courses. Two 3-year trials
      suggested that the drug also has joint structure-modifying properties and,
      therefore, might be useful as a disease-modifying agent in osteoarthritis.

PMID- 17515292
TI  - In vivo pharmacokinetics and toxicity of a novel hydrophilic oral formulation of
      the potent non-nucleoside reverse transcriptase inhibitor compound N'-[2-(2
      thiophene)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea (HI-443).
AB  - The thiophene ethyl thiourea (TET) compound N'-[2-(2-thiophene)ethyl]-N'-[2-(5
      bromopyridyl)]-thiourea (HI-443) is a potent non-nucleoside reverse transcriptase
      inhibitor (NNRTI). The pharmacokinetics of 17 different novel oral formulations
      of HI-443 were compared in an attempt to identify the most suitable dosage form
      for clinical use in HIV-infected persons. Plasma concentrations of HI-443 were
      monitored in mice after administration of the drug using these 17 different
      formulations at three time points. Two-way ANOVA showed highly significant
      formulation (p < 0.0001), time (p < 0.0001) and formulation*time interaction
      effects (p = 0.0003). Planned linear contrasts were performed to identify which
      formulations showed the highest bioavailability at 10, 30, 60 min and at all time
      points relative to DMSO alone. A significant positive regression was observed
      comparing bioavailibility of HI-443 at 10 min and hydrophilic-lipophilic balance
      (HLB) values of the formulations (R2 = 26%, p < 0.0001). The results showed that
      formulations that were hydrophilic, containing PEG400 and propylene glycol, gave
      the highest overall drug concentrations over the 60-min time period. The lead
      oral formulation of HI-443 exhibited a very favorable toxicity profile in BALB/c
      mice.

PMID- 17515293
TI  - Comparative pharmacokinetics of two tablet formulations of amoxicillin:
      bioequivalence assessment.
AB  - The aim of the present study was to compare the bioavailability of amoxicillin
      (CAS 26787-78-0) from two different amoxicillin tablets (Demoksil 1 g tablet as
      test preparation and 1 g tablet of the originator product as reference
      preparation). The study was conducted according to an open-label, randomised two
      period cross-over design with a wash-out phase of 4-7 days. Blood samples for
      pharmacokinetic profiling were taken up to 10 h post-dose, and amoxicillin plasma
      concentrations were determined with a validated LC-MS/ MS method. Maximum plasma
      concentrations (C(max)) of 13,296.4 ng/ml (test) and 12,797.7 ng/ml (reference)
      were achieved. Areas under the plasma concentration-time curve (AUC(0-infinity))
      of 39,556.7 ng x h/ml (test) and 38,599.1 ng x h/ml (reference) were calculated.
      The median t(max) was 1.62 h (test) and 1.54 h (reference). Plasma elimination
      half-lives (t(1/2)) of 1.64 h (test) and 1.65 h (reference) were determined. Both
      primary target parameters, AUC(0-infinity) and C(max) were tested parametrically
      by analysis of variance (ANOVA) and the 90% confidence intervals were between
      96.76%-108.46% (AUC(0-infinity)) and 97.80%-111.98% (C(max)). Bioequivalence
      between test and reference preparation was demonstrated since for both
      parameters, AUC and C(max) the 90% confidence intervals of the T/R-ratios of
      logarithmically transformed data were in the generally accepted range of 80%
      125%.

PMID- 17515294
TI  - Bioequivalence study of sultamicillin suspensions.
AB  - Sultamicillin (CAS 76497-13-7) is a prodrug combination of ampicillin (CAS 69-53
      4) and sulbactam (CAS 68373-14-8), with the antibiotic ampicillin and the beta
      lactamase inhibitor sulbactam chemically linked as double ester. The present
      study was performed to investigate the relative bioavailability and to assess the
      bioequivalence of two different sultamicillin suspensions (Devasid 250 mg/5 ml as
      test preparation and 375 mg/7.5 ml of the originator product as reference
      preparation). Twenty-four healthy male volunteers received equal doses of the
      sultamicillin preparations according to an open, randomised, single-dose, two
      period cross-over design with a wash-out phase of 7 days. Blood samples for
      pharmacokinetic profiling were taken up to 8 h post-dose, and ampicillin and
      sulbactam plasma concentrations were determined with a validated LC-MS/MS method.
      Maximum plasma concentrations (C(max)) of 11,267.4 ng/ml (ampicillin, test),
      10,864.4 ng/ml (ampicillin, reference), 6,360.6 ng/ml (sulbactam, test and
      6,410.7 ng/ml (sulbactam, reference) were achieved. Areas under the plasma
      concentration-time curve (AUC(0-infinity) of 17,512.9 ng x h/ml (ampicillin,
      test), 18,388.0 ng x h/ml (ampicillin, reference), 10,971.7 ng ng x h/ml
      (sulbactam, test) and 11,181.2 ng x h/ml (sulbactam, reference) were calculated.
      The median t(max) was 0.69 h (ampicillin, test), 0.85 h (ampicillin, reference),
      0.72 h (sulbactam, Devasid) and 0.83 h (sulbactam, reference). Plasma elimination
      half-lives (t(1/2)) of 1.04 h (ampicillin, test), 1.03 h (ampicillin, reference),
      1.26 h (sulbactam, Devasid) and 1.00 h (sulbactam, reference) were determined.
      Both primary target parameters AUC(0-infinity) and C(max) of ampicillin and
      sulbactam were tested parametrically by analysis of variance (ANOVA) and the 90%
      confidence intervals were between 84.58%-117.80% (AUC(0-infinity), ampicillin),
      92.37%-119.93% (C(max), ampicillin), 85.81%-120.50% (AUC(0-infinity), sulbactam)
      and 88.41%-117.57% (C(max), sulbactam). Bioequivalence between test and reference
      preparation was demonstrated since for both parameters AUC and C(max) the 90%
      confidence intervals of the T/R-ratios of logarithmically transformed data were
      in the generally accepted range of 80%-125%.

PMID- 17515295
TI  - [On-going investigations on efficacy and safety profile of a herbal drug
      containing nasturtium herb and horseradish root in acute sinusitis, acute
      bronchitis and acute urinary tract infection in children in comparison with other
      antibiotic treatments].
AB  - PATIENTS AND METHODS: In this study which was carried out in the period between
      1st May until 4th October 2006 in 65 study sites as a prospective cohort study in
      858 children, adolescents and juveniles in the age between 4 and 18 years who
      consulted the physician due to an acute sinusitis, acute bronchitis or acute
      urinary tract infection (UTI). Data of in total 858 patients were recorded. The
      patients were treated either with the herbal drug preparation Angocin Anti-Infekt
      N (test group, n = 523, 61%) or with a standard antibiotic (control group, n =
      335, 39%) according to the decision of the physician. The duration of treatment
      as well as the dosage was determined by the physician. 297 patients suffering
      from acute sinusitis (197 test group 66%, 100 control patients 34%), 290 patients
      suffering from acute bronchitis (178 test group 61%, 112 control patients 39%)
      and 271 patients with acute urinary tract infection (148 test group 55%, 123
      control patients 45 %) were included. The patients recorded in a diary the
      utilization of the medication, concomitant procedures and adverse events (AEs).
      The physician recorded at study start and at the end of the study the compliance
      in a standardised form. Single symptoms were recorded according to their
      intensity with a score ranging from 0 = no symptom to 3 = severe symptoms. At the
      end of the study (disease free or after 7-14 days) the physicians finally judged
      on the course of the treatment as well on the efficacy as observed. The patients
      recorded their satisfaction with the treatment. Primary efficacy criterion was
      the change of the complaints quantified by the change of the relative symptom
      score average over all symptoms between result at study start and study end
      related to the baseline value. RESULTS: The two therapy groups differ in their
      basis data with regard to the mean age (test group 12.2 years, control group 13.5
      years; p > 0.001) and the frequency of concomitant diseases (test group 6.3%,
      control group 2.4%; p = 0.008). At start of treatment the complaints in the test
      group were significantly less severe (mean of the complaint score 1.67) compared
      to the control group (mean 2.00; p > 0.001). At the end of treatment there were
      no significant differences in the mean complaint score between the groups (test
      group 0.41, control group 0.49; p = 0.722). The mean reduction of the complaint
      score expressed in percentages was for the indication acute sinusitis in the test
      group 84.8% and in the control group 85.5%, for the indication acute bronchitis
      in the test group 82.1% and in the control group 77.7% and for the indication
      acute urinary tract infection in the test group 89.9% and in the control group
      93.1%. In total the mean reduction of the complaint score for the test group was
      85.3% and in the test group 85.7% (p = 0.828). The 95% confidence interval for
      difference of the expected reductions between test group and control group ranged
      from -3.87% up to 3.10%. With a border of +/- 10% the mean reduction for both
      groups is equivalent, and more importantly non-inferior for the test group
      compared with the control group. Adverse events were recorded for 3 patients
      (0.6%) of the test group and for 14 patients (3.9%) of the control group (p =
      0.001). In conclusion it was demonstrated that therapy with the herbal drug
      preparation in the indications acute sinusitis, acute bronchitis and acute
      urinary tract infection is--with regard to efficacy--comparable to a treatment
      with standard antibiotics. The test preparation displayed in all indications a
      significantly lower potential for adverse events compared to a treatment with
      standard antibiotics and, therefore, a better safety profile could be concluded.

PMID- 17515296
TI  - Fetal nuchal translucency thickness.
AB  - In the early 1990s Nicolaides introduced screening for trisomy 21 by fetal nuchal
      translucency thickness measurement with ultrasound between 11-13(+6) weeks.
      Already in 1866 L. Down noted that common features of patients with trisomy 21
      are a skin being too large for the body and a flat face with a small nose. While
      detection rates for trisomy 21, given an invasive testing rate of 5%, were only
      30% for screening by maternal age and 65% for screening by maternal serum triple
      test, the detection rate for screening by nuchal translucency combined with
      maternal age was 75% and this could be increased to 90% in combination with
      maternal serum screening (serum B-human chorionic gonadotropin and pregnancy
      associated plasma protein-A) at 11-13(+6) weeks. The additional soft markers in
      the first trimester are the fetal nasal bone, the Doppler velocity waveform in
      the ductus venosus and tricuspid regurgitation and these markers can be used to
      further increase the detection rate of trisomy 21. In addition increased nuchal
      translucency thickness can also identify other chromosomal defects (mainly
      trisomy 13 and 18 and monosomy X) and major congenital malformations (mainly
      cardiac defects) and genetic syndromes.

PMID- 17515297
TI  - Distal monosomy 16p13.3/distal trisomy 2p24.2-pter: molecular-cytogenetic
      characterisation and phenotype.
AB  - We describe a 4-year-old boy with various facial dysmorphic features such as
      downslanting palpebral fissures, ptosis, hypertelorism, broad nasal bridge, small
      and low-set ears, broad philtrum, and micrognathia. In addition, profound mental
      retardation, myopia, muscular hypotonia as well as genital and cardiovascular
      abnormalities are also present. Refinement of the breakpoints by cytogenetic
      techniques, in particular the increase of banding resolution in conventional
      cytogenetic analysis, has enabled the correct diagnosis, as proven by
      fluorescence in situ hybridisation (FISH) using whole chromosome painting and
      single copy probes. We were able to demonstrate an unbalanced translocation that
      the patient inherited from his father resulting in a submicroscopic monosomy
      16p13.3 and a trisomy 2p24.2-pter.

PMID- 17515298
TI  - Expressive language in persons with Prader-Willi syndrome.
AB  - The aim of the present study was to add to the delineation of the prevalence and
      nature of language difficulties in Prader-Willi syndrome (PWS). Subjects of this
      study were 32 Dutch speaking individuals (20 males, 12 females), with
      chronological ages ranging from 4;6 to 29,5 and total IQ ranging from 40 to 94.
      Spontaneous speech samples were subjected to a consensus orthographic
      transcription and analysed by means of TOAST, a Dutch standardized diagnostic
      instrument to investigate spontaneous language production. It was found that
      expressive language is usually problematic in PWS. Clearly, different linguistic
      levels are affected and some levels are more prone to difficulty than others. In
      general morphosyntax appears to be poor, whereas phonology is fairly good.
      Difficulties with vocabulary and/or pragmatics may be present as well.
      Considerable inter-individual variation was found as to the severity of the
      language problems.

PMID- 17515299
TI  - Phenotypic and cytogenetic spectrum of 9p trisomy.
AB  - Trisomy 9p is one of the most frequent autosomal anomalies compatible with long
      survival rate. The spectrum of clinical severity in trisomy 9 roughly correlates
      with the extent of trisomic chromosome material. Trisomy 9p is a clinically well
      delineated syndrome and of all stigmata craniofacial dysmorphism is most
      specific. In this study we report five cases with de novo trisomy 9p. The study
      aimed at the identification of the genotype/phenotype correlations in patients
      with different breakpoints. GTG banding, DAPI stain, whole chromosome paint,
      centromere, telomere and 9p21 specific locus probes demonstrated that partial
      trisomy 9p in case 1 was due to isochromosome 9p with translocation of the long
      arm of re-arranged chromosome 9 onto the short arm of chromosome 13, cases 2 and
      3 had intrachromosomal duplication of the short arm of chromosome 9
      [dup(9)(p21p24)], case 4 had "classical" 9p trisomy and case 5 had duplication of
      whole short arm and part of the long arm of chromosome 9 (partial 9 trisomy).
      Although cases 1 to 4 had trisomy involving 9p, cases 1 and 2 exhibited the
      classical clinical manifestations of 9p trisomy, while cases 3 and 4 had
      additional features overlapping with Coffin-Siris syndrome. The present study
      strengthens the association of Coffin-Siris syndrome and 9p, the significance of
      such observations may point to possible gene location of Coffin-Siris syndrome on
      9p. Case 5 had additional manifestations more than those typical of trisomy 9p
      which could be due to duplication of 9q21 region. Wide gap between 1st and 2nd
      toes, observed in the studied cases, can be added to the phenotype of this
      trisomy. Three of our cases had brain malformations, case 3 had dilated
      ventricles with hypogenesis of corpus callosum, case 4 had agenesis of corpus
      callosum, and case 5 had Dandy-Walker malformation. We also suggest that dosage
      effects of genes located in 9pter-q22 contribute to the etiology of Dandy-Walker
      syndrome. We recommend MRI studies as a routine in all cases with trisomy 9p.

PMID- 17515300
TI  - Prenatal diagnosis and genetic counseling of mucopolysaccharidosis type II
      (Hunter syndrome).
AB  - We present prenatal diagnosis of mucopolysaccharidosis type II (MPS II) (Hunter
      syndrome) and demonstrate marked mucopolysaccharide deposition in multiple vital
      organs in a 22-gestational-week affected fetus. Level II ultrasound showed
      cardiomegaly and hepatomegaly. Histological examinations of the fetal vital
      organs manifested marked mucopolysaccharide deposition. We suggest that any
      therapeutic approach and counseling for prenatally diagnosed MPS II should
      consider the early signs of in utero marked mucopolysaccharide storage.

PMID- 17515301
TI  - Complex chromosomal rearrangements.
AB  - Complex Chromosomal Rearrangements (CCRs) are constitutional structural
      rearrangements involving three or more chromosomes or having more than two
      breakpoints. CCRs preferentially occur during spermatogenesis and are transmitted
      in families through oogenesis. Recent investigation showed that CCRs are more
      complex and more common than initially appreciated. Here 1 present an overview of
      CCRs, including the important impact of CCRs in fertility, the mechanism of their
      development, the various meiotic errors that can occur and their consequences.
      The review also discusses the differential transmission of CCRs in males and
      females, the incidence of pregnancy outcomes of CCR carriers, genetic counseling
      and prenatal diagnosis.

PMID- 17515302
TI  - A new case of Martsolf syndrome.
AB  - Martsolf syndrome is an autosomal recessive syndrome characterized by
      microcephaly, mental retardation, cataract, hypogonadism and short stature. A
      seven-year-old boy was admitted to the hospital with growth retardation and
      difficulties in walking. His parents were first cousins. Bilateral lens
      extraction was performed during infancy because of congenital cataract. On
      physical examination he had short stature, microcephaly, micropthalmia,
      hypogonadism, mental retardation. Brain magnetic resonance imaging revealed
      alterations in the white matter. Up to date very few cases with this syndrome
      have been reported. This is the first case described in the Turkish population
      and may add valuable information to the literature.

PMID- 17515303
TI  - Duane anomaly, meningomyelocele, dextroposition of heart and localized
      vertebrocostal alterations with associated anomalies in a girl.
AB  - Vertebral and rib anomalies occur because of defects at different stages of
      embryo development and result in different malformations. Developmental field
      defects are the term to describe the alterations in the biological units which
      occur because of defects in the pattern formation. Short trunk dwarfism
      associated with vertebral and rib anomalies is one of the well-known conditions
      described under various names. Here we report on a 20-month-old female with short
      trunk dwarfism involving an asymmetrically malformed thorax with kyphoscoliosis
      presenting skeletal anomalies of spine and ribs and additional multiple
      associated anomalies such as downslanting palpebral fissures, long philtrum, high
      palate, rocker bottom feet, dextroposition of heart, cascade stomach,
      retroposition of bulbi duodeni and bilateral renal cortical thinning.
      Ophthalmological examination revealed Duane anomaly. No mutation was detected in
      the analysis of the DLL3 gene. The malformations in the patient are related to
      different progenitor fields in the early development of the embryo and the
      presented combination of Duane anomaly with the associated anomalies has not been
      reported in the literature.

PMID- 17515304
TI  - SED-brachydactyly and distinctive speech: report of two new cases.
AB  - We describe two unrelated patients and the mother of one of them showing clinical
      and radiological features as those previously described in the spondyloepiphyseal
      dysplasia-brachydactyly and distinctive speech (SED-BDS, also named Fantasy
      Island syndrome or Tattoo dysplasia) clinically characterized by short stature
      with acral shortness, distinctive face, mild blepharophimosis, upslanted
      palpebral fissures, abundant eyebrows and eyelashes, thick and abundant hair and
      coarse voice; and radiologically by brachymetacarpalia, brachymetatarsalia and
      brachyphalangia of all fingers and toes, short and broad long bones with normal
      morphology and small pelvis. The clinical and radiological features present in
      mother and son suggest a probable autosomal dominant mode of inheritance and
      variable expressivity.

PMID- 17515305
TI  - First report of a patient with a mixoploidy 47,XXX/94,XXXXXX.
AB  - We present a 16 years old female with a chromosomal mixoploidy and multiple
      phenotypic anomalies. Peripheral blood G-band karyotype was 47,XXX and her skin
      fibroblast karyotype revealed a mosaic with a 47,XXX cell line in 88% of
      metaphases and a 94,XXXXXX cell line in 12% of metaphases, consistent with a
      hypertetraploidy. The most prominent clinical signs were: short stature, left
      upper limb asymmetry, senile-like appearance, generalized hypertrichosis, and
      small hands and feet. Radiological examination showed bone dysplasia. The result
      of molecular studies demonstrated that the patient inherited the two X
      chromosomes from the mother and one from the father, indicating that her 47,XXX
      trisomy resulted from an oogenesis error in the first meiotic division. The
      94,XXXXXX cell line was likely the result of a cytokinesis error. To our
      knowledge, this is the first documented patient with a trisomy and a
      hypertetraploidy.

PMID- 17515306
TI  - Second-trimester diagnosis of limb-body wall complex with literature review of
      pathogenesis.
AB  - Three fetuses having limb-body wall complex (LBWC) with craniofacial defects and
      9 fetuses having LBWC without craniofacial defects were diagnosed and delivered
      in the second trimester at Mackay Memorial Hospital during the period January
      1990 - May 2006. Cases of LBWC with craniofacial defects showed severe anomalies
      of the upper limbs, craniofacial defects, constrictive amniotic bands and
      cranioplacental attachment, whereas, cases of LBWC without craniofacial defects
      presented major anomalies of the lower limbs, abnormal genitalia, anal atresia,
      renal defects, abdominoplacental attachment and umbilical cord abnormalities. The
      perinatal findings of LBWC with or without craniofacial defects were compared and
      the pathogenesis was discussed.

PMID- 17515307
TI  - Kabuki syndrome: description of a 2-year old Roumanian boy and review of the
      literature.
AB  - We report on a 2-year-old boy presenting the cardinal features of the Kabuky
      syndrome i.e. peculiar face, short stature moderate mental retardation, padded
      fingers, padded toes and shawl scrotum. Karyotype was 46, XY. Fish tests for
      microdeletion: 22q11 and 16q (Rubinstein Tayby) were normal.

PMID- 17515308
TI  - Distal joint contractures, mental retardation, characteristic face and growth
      retardation: Chitayat syndrome revisited.
AB  - We report on a patient with congenital distal limb contractures, characteristic
      face, prominent metopic sutures, narrow forehead, severe psychomotor and growth
      retardation, white matter lesions and failure to thrive. The child has many
      overlapping features with those reported previously by Chitayat. We suggest that
      the central nervous anomalies are responsible for the congenital contractures in
      Chitayat syndrome.

PMID- 17515309
TI  - Aortic and pulmonary valve stenosis in a neonate: a new finding of prune belly
      syndrome?

PMID- 17515310
TI  - Evidence-based practice is paramount.

PMID- 17515311
TI  - SANTA vs. public tuberculosis hospitals: the patient experience in the Free
      State, 2001/2002.
AB  - This paper reflects on the appropriateness of the decision to close down a non
      governmental organisation (NGO), state-aided tuberculosis (TB) hospital in the
      Free State in 2003. Henceforth hospitalisation of TB patients would take place at
      public district hospitals. A survey conducted late-2001/early-2002 revealed a
      more positive patient experience of hospitalisation for TB in public hospitals
      than in the NGO hospital. Consideration of the patient experience serves to
      inform the debate concerning continued outsourcing of TB hospital care to NGOs in
      South Africa. This study discusses comparative findings in respect of patients'
      biographic and socio-economic characteristics, health beliefs, satisfaction with
      hospitalisation, experience of stigmatisation, adherence to treatment and
      absconding from hospital.

PMID- 17515312
TI  - A comparative study of adoloscents' perceived stress and health outcomes among
      adolescent mothers and their infants in Lesotho.
AB  - PURPOSE: The purpose of this study was to compare perceived stress in general,
      stress due to pregnancy, and post partum complications between a group of
      unmarried adolescent first-time mothers and a group of married adolescent first
      time mothers. Never-pregnant adolescents served as a comparison group on
      perceived stress. Health outcomes of infants of the two groups of adolescent
      mothers were also compared on birth weight, nutritional status (weight gain) and
      immunization status. METHODS: The study design was non-experimental, comparative
      and descriptive. A convenience sample of dyads of 64 unmarried adolescent mothers
      and their infants, 64 married adolescents and their infants, and 64 high school
      students participated in this study. Data were collected in 3 hospitals, 2 health
      centres (clinics) and a high school in Lesotho. The differences between the three
      groups of adolescents in perceived stress, were determined using ANOVA. The t
      test was used to determine the differences between the group of unmarried
      adolescent mothers and the group of married mothers on stress due to pregnancy.
      The difference in postpartum complications between these two groups of adolescent
      mothers was determined using Chi-square. The t-test was also used to determine
      differences in birth weight, nutritional status and immunization status between
      the group of infants of unmarried mothers and infants of married mothers.
      FINDINGS: Findings of this study revealed significant differences in perceived
      stress between both groups of adolescent mothers and the group of never pregnant
      adolescents (p < .0001). The Chaffe' test revealed that never pregnant
      adolescents had lowest levels of perceived stress than both groups of adolescent
      mothers (p < .0001). Both groups of adolescent mothers had high levels of stress
      due to pregnancy and the difference between the two groups was non-significant.
      No differences were observed between infant health outcomes of unmarried mothers
      and infants of married mothers. The infants of both groups were generally healthy
      and the majority of them had appropriate type and doses of immunizations six
      weeks post birth. CONCLUSION: Adolescent mothers in the low lands of Lesotho
      perceive pregnancy to be a stressful event despite marriage. Therefore
      adolescents should be discourage from early childbirth. Policy makers need to
      come up with gender sensitive policies that will make it easier for girls who get
      pregnant to continue with their education, so that they may be productive and
      self-reliant.

PMID- 17515313
TI  - Perceptions of adolescents in low resourced areas towards pregnancy and the
      Choice on Termination of Pregnancy (CTOP).
AB  - Teenage pregnancy, unsafe abortion methods and the high incidence of HIV
      infections among young people are of great concern to the South African public.
      Due to the lack of accurate information and understanding, some adolescents are
      forced to succumb to early motherhood from unplanned pregnancies or opt for back
      street abortion with at times fatal results. A qualitative exploratory study was
      conducted in 2003 to determine the adolescents' perceptions towards factors on
      the Choice on Termination of Pregnancy (CTOP) and the constraints in accessing
      TOP services. A purposive sampling technique that enabled experts such as health
      workers to identify suitable candidates for the investigation was employed.
      Twenty-four (24) adolescents residing in the predominantly rural area of Nkumpi
      Lepelle in the Limpopo Province agreed to participate in the focus group
      interviews. The major findings indicated that most adolescents were uninformed
      about CTOP. This is attributed to the lack of coordination among health
      professionals and educators in the dissemination of information. The overwhelming
      majority of the respondents expressed discomfort at receiving termination of
      pregnancy services from the local public clinics and hospitals as they regarded
      such facilities as youth unfriendly. The adolescents also required provision of
      pre- and post-counselling services for adolescents who would like to terminate
      pregnancy. The following hypotheses were formulated for future in-depth studies:
      If adolescents continue to lack information about CTOP, they will not be able to
      utilize available services to terminate unplanned and unwanted pregnancies. If
      CTOP services remain inaccessible to the youth, the problem of backstreet
      abortion will not be eradicated.

PMID- 17515314
TI  - Beliefs of grade six learners' regarding adolescent pregnancy and sex.
AB  - Escalating adolescent pregnancy and risky sexual behaviour is becoming more
      common amongst young adolescents and especially amongst black adolescents in
      South Africa. Statistics confirm that South African adolescents as young as
      fourteen are already sexually active and become pregnant. The decision to become
      sexually active with resulting adolescent pregnancy whether planned or not, are
      directly influenced by the teenager's beliefs. A person's beliefs consist of a
      person' own individual beliefs or attitude as well as what the individual
      subjective norm which the individual perceive as other people's beliefs regarding
      the same object of reason. The aim of the study was to describe the attitude of
      black grade six learners under the age of fourteen, towards adolescent pregnancy
      and sex. A quantitative descriptive research design was used. Results were
      clustered according to demographic variables as well as beliefs that consist of
      attitude and subjective norm. Findings provided insight into the beliefs of grade
      six learners regarding sex and adulthood, the roll of peer pressure,
      relationships of adolescent parents, social interaction of teenage parents,
      ability of adolescent parent's ability to provide in the needs of the baby, the
      adequacy of a child support grant to raise a baby as well as the levels of
      education of adolescent parents. This article provide a detailed reflection on
      these results and propose off a doll parenting intervention strategy as means of
      modification of attitude and subjective norms of grade six learners in order to
      alter sexual behaviour.

PMID- 17515315
TI  - Integration of research and nursing experiential learning: a case study.
AB  - Teaching research to undergraduates has it own challenges and involving
      undergraduates in research practical experience is just one of those challenges.
      As nursing students are in the process of becoming professional nurses, knowledge
      and skills in research are specific outcomes of the curriculum. One of the
      outcomes of the B Tech Nursing Science programme offered by the Tshwane
      University of Technology states that for the baccalaureate nursing programme
      include analysis, interpretation and utilisation of a range of research findings
      in scientific nursing and midwifery care as well as the development of a research
      protocol in a given context. In an effort to ensure that students would
      experience research as an essential part of their daily activities, an integrated
      approach is suggested whereby the nursing experiential learning opportunities are
      also research experiential learning opportunities. Using the integration
      strategy, research theory come 'alive' for the students. The integration approach
      is uncomplicated and transferable to any other discipline. The case study
      presented is the second year nursing students using school nursing experiential
      learning as a research project. The second year nursing students have a community
      focus during their second year and one of the experiential learning opportunities
      is school health nursing in a primary school in Tshwane. The results of the
      school health survey are presented. The students developed a health education
      intervention based on the research results.

PMID- 17515316
TI  - An assessment of the implementation of the provincial cervical screening
      programme in selected Primary Health Care Clinics in the Ilembe Region, KwaZulu
      Natal.
AB  - Cervical cancer is almost completely preventable, yet it is the second most
      prevalent cancer amongst women in South Africa. KwaZulu-Natal (KZN) in particular
      has a high mortality rate of cervical cancer and 1: 40 women die from cancer of
      the cervix. Therefore, in 1997 a cervical screening policy and programme was
      implemented in the province. The purpose of the study was to evaluate the
      implementation of selected aspects of the Provincial cervical screening programme
      in selected Primary Health Care (PHC) clinics in Ilembe Region, KZN. Results
      indicated that there was a lack of resources needed for implementing the
      programme in rural clinics compared to urban clinics. However, all clinics in the
      study had an adequate supply of the drugs needed for the treatment of abnormal
      smears. On reviewing the records, the researcher noted that most of the results
      indicated that smears had adequate cells needed for analysis. However, the
      results indicated that there was a problem with follow-up of clients with
      abnormal smears. Feedback to the clinics from the referral hospital regarding the
      outcome of the visit was inadequate. The results indicated that the mechanisms of
      record keeping were inadequate. Therefore, the above results indicate that
      problems exist at the selected PHC clinics that may result in ineffective
      implementation of the cervical screening programme.

PMID- 17515317
TI  - Management of the oral manifestations of HIV/AIDS by traditional healers and care
      givers.
AB  - In many communities of South Africa, traditional healers are often the only means
      of health care delivery available. The level of knowledge and ability to
      recognize oral lesions of 32 traditional healers and 17 care-givers were assessed
      after a two-day workshop. The data collection instrument was a structured
      questionnaire, complimented by enlarged clinical photographs of the common oral
      manifestations of HIV/AIDS. Prior to the workshop, 46 (93.9%) of the 49
      respondents had never had any formal information on oral health and 43 (87.8%)
      were unfamiliar with the symptoms of oral diseases. Thirty-five (71.4%)
      recognized bleeding gums from A4-size photographs and 11 (22.4%) recognized oral
      thrush. The recognition of other oral manifestations of HIV/AIDS were; oral hairy
      leukoplakia (41.0%), angular cheilitis (43.6%), herpes virus infection (56.4%),
      oral ulcerations (56.8%), and in children, parotid enlargement (27.3%), and
      moluscum contagiosum (56.8%). Traditional healers and caregivers constitute an
      untapped resource with enormous potential. A positive bridge should be built to
      link traditional healing with modem medicine in the struggle against HIV/AIDS.

PMID- 17515318
TI  - Professional nurses' perception of the implementation of quality circle programme
      in a public hospital in the Eastern Cape Province.
AB  - A qualitative research design that is explorative, descriptive and contextual in
      nature was employed in order to understand and describe the professional nurses'
      perception of the implementation of a quality circle programme in a public
      hospital in the Eastern Cape Province. The data-collection techniques were
      individual semi-structured interviews and field notes. The sample was drawn from
      a population of 425 Xhosa-speaking professional nurses employed in this
      institution. The sample comprised eight (8) professional nurses all of whom
      volunteered for in-depth individual semi-structured interviews. All the
      respondents answered one question: How do you perceive the implementation of the
      quality circle programme in your hospital? During data collection and analysis
      only one theme emerged, namely the perception of quality circle as a forum for
      discussing patient care problems and future plans. There were four broad
      categories in this theme, namely. Staff empowerment. Teambuilding in the nursing
      discipline. Maintenance of standards by nurses. Challenges to the momentum of a
      quality circle programme. It is recommended that all three tiers of nursing
      management be involved in the quality circle programme to improve interpersonal,
      interdepartmental and intradepartmental communication and concomitantly the
      nursing care.

PMID- 17515319
TI  - Involvement of males in promoting reproductive health.
AB  - At the international conference on Population and Development held in Cairo 1994,
      specific aspects of reproductive health addressed endorsed among others, were
      that unwanted pregnancies must always be given the highest priority and that
      every attempt should be made to eliminate the need for abortion. This paper
      focused on the involvement of males in promoting reproductive health through
      prevention of unplanned and unwanted pregnancies. A total of 71 males (48 adults
      and 23 adolescents) were selected conveniently from two health care centres,
      North of Tshwane, Gauteng province. Structured questionnaires having open and
      closed questions were used for data collection. Results indicated that most males
      (young and old) had general information about contraceptives and common side
      effects associated with contraceptive use. Despite this knowledge, only (29.2%)
      adults and almost half the number (50.0%) adolescents reportedly used condoms
      every time when having sex, whilst (35.0%) adults and only (13.6%) adolescents
      had never used condoms when having sex. Generally, males felt positive and wished
      to be involved in issues affecting their relationships, such as open
      communication about contraceptives used by their partners, discussing
      contraceptive problems together, planning families jointly with partner only,
      being informed about contraceptive failures and also playing a role in resolving
      such problems. Recommendations were made to encourage more visible involvement of
      males in promoting sexuality issues and reproductive health.

PMID- 17515320
TI  - Shangaan patients and traditional healers management strategies of hypertension
      in Limpopo Province.
AB  - The study explored the cultural care beliefs, values and attitudes of Shangaans
      patients' and traditional healers' management strategies of hypertension in the
      Limpopo Province. The study aimed to describe the cultural values, beliefs and
      practices including taboos, rituals and religion within the world-view of the
      Shangaans. The study was undertaken in the Mopani region of the Greater Giyani
      area, with the purpose of recommending improvements to patient care in this area.
      Data collection was done by conducting focus groups and individual interviews.
      The following themes emerged. Hypertension. The traditional healer: the
      instrumental role. Traditional medicine versus Western medicine. Magico-religious
      healings. Cultural beliefs of Shangaans and hypertension. Experiences of
      hypertensive patients with regard to traditional healers and hypertension.

PMID- 17515321
TI  - The life-world of mothers who care for mentally retarded children: the Katutura
      township experience.
AB  - This article reports on a research study done in Katutura Township, near
      Windhoek. A qualitative, exploratory, descriptive and contextual design was
      followed to answer the research question investigating experiences of mothers
      caring for mentally retarded children at home. Phenomenological interviews were
      conducted with a purposefully selected sample of twelve mothers. The meaning of
      their experiences was analysed by using Teschxs method (1990 in Creswell,
      1994:155) of analysing qualitative data. The results indicated various emotions
      and challenges experienced by these mothers during the care of their children.
      Feelings of shock, despondency and sadness dominated the early stages when the
      retarded children were still young. During later years, as the children were
      growing up, the mothers felt shame, fear, frustration, anger, disappointment and
      worry. However, acceptance followed, as the children grew older. Stigma seemed to
      affect all the respondents. Support in any form or lack thereof seemed to be the
      decisive factor-positioning mothers along a continuum of two extremes, namely
      despairing isolation and integrated happiness. Recommendations were made
      regarding the improvement of heath care services and education of the mothers and
      their families.

PMID- 17515322
TI  - The effect of pH on cyclodextrin complexation of trifluoperazine.
AB  - The characteristics of host-guest complexation between cyclodextrins (beta-CD, DM
      beta-CD, HP-beta-CD) and protonated (pH 1.9, 6.2) or basic (pH 10.2) forms of
      trifluoperazine (TF) were investigated by spectrometric method. The association
      constants of complexes obtained at different temperatures and pH were calculated
      using Scott's equation and the thermodynamic parameters (deltaH, deltaS and
      deltaG) associated with the inclusion process were determined from Van't Hoff
      plot. The influence of pH and CD complexation on photostability of TF in
      solutions of different pH was followed. It was found that the photochemical
      decomposition of TF alone and in the presence of CD proceeds according to the
      first order reaction. It was also established that the increase in the TF
      photostability was dependent on the stability of TF-CD association. Spatial
      configuration of obtained complexes has been proposed on the basis of 2D NMR
      technique.

PMID- 17515323
TI  - A simpler and faster capillary electrophoresis method for determination of
      mianserin enantiomers in human serum.
AB  - A stereospecific sample stacking capillary zone electrophoresis method is
      described for determination of S(+) and R(-) enantiomers of mianserin
      (1,2,3,4,10,14b-hexahydro-2-methyldibenzo[c,f]pyrazino[1,2-a]azepine) in human
      serum. The enantiomers of mianserin were extracted from human serum in one step
      extraction procedure using the mixture n-heptane:ethyl acetate (80:20, v/v).
      After separation of layers and freezing at -28 degrees C the organic layer was
      decanted and evaporated under a stream of nitrogen. The sample was dissolved in
      the mixture: water:methanol:acetonitrile (2:1:1, v/v/v). Separation was conducted
      in an aqueous solution of phosphoric acid (0.075M) adjusted to pH = 3.0 with
      concentrated triethylamine, and 2 mmole/L of 2-hydroxypropyl-beta-cyclodextrin.
      The analytes were measured by ultraviolet detection at 214 nm after separation on
      a Fused-Silica eCAP capillary. Clozapine was used as an internal standard.
      Recovery of the enantiomers from serum ranged from 82.94 to 90.37%. Total time of
      analysis was 49 minutes, whereas the other methods needed up to 100 minutes.

PMID- 17515324
TI  - Topoisomerase II alpha expression and cytotoxicity of anthracyclines in human
      neoplastic cells.
AB  - Topoisomerase II is ATP dependent enzyme that catalyzes DNA strand passage, the
      pivotal process in replication, transcription, recombination etc. As part of this
      breakage and religation process the intermediate generated is a cleavable complex
      between DNA and topoisomerase II. This complex is the target for topoisomerase II
      inhibitors like epipodophyllotoxins, actinomycin D or anthracyclines.
      Stabilization of cleavable complexes by the topoisomerase II inhibitors leading
      to DNA lesions and next to apoptosis is the most common mechanism of drug
      resistance reflected in reduced formation of the complexes due to decreased
      amounts and/or activity of topoisomerase II. The aim of this study was to
      characterize human melanoma and human cervix carcinoma cells differing in
      sensitivity to doxorubicin and anthracycline analogs, annamycin and WP903 for
      topoisomerase IIalpha protein and gene expression with use of Western blot and RT
      PCR. As shown, no significant differences in topoisomerase IIalpha protein level
      were noted between the cell lines tested. These results were confirmed at the
      gene expression level. The current study points to the fact that topoisomerase
      IIalpha protein or gene expression are not the reliable marker of cell
      sensitivity to anthracyclines but these observations do not exclude the potential
      mutations in topoisomerase IIalpha gene or some postranslational changes in that
      protein which requires further studies.

PMID- 17515325
TI  - Preliminary evaluation of antioxidant activity of some 1-(phenoxyethyl)
      piperazine derivatives.
AB  - The antioxidant properties of appropriate 1-(phenoxyethyl)-piperazine derivatives
      possessing significant hypotensive activity in normotensive rats were measured in
      human venous blood samples, in vitro. Ferric reducing ability of plasma (FRAP)
      was measured in plasma, superoxide dismutase (SOD) and catalase (CAT) activities
      were determined in red blood cell hemolysates. Antioxidant profile of 1
      (phenoxyethyl)-piperazine derivatives was compared to Trolox and Resveratrol. The
      compounds were investigated in concentrations from 10(-8) to 10(-4) mol x L(-1).
      The most promising compounds were 1-[(4-methyl)- and 1-[(2,6-dimethyl)
      phenoxyethyl]-piperazine derivatives [1, 2] which increased SOD activity and
      total antioxidant capacity (TAC). An addition of chlorine atom to methyl-phenoxy
      moiety decreased antioxidant properties.

PMID- 17515326
TI  - Synthesis and pharmacological evaluation of 2-hydroxymethylbenzamides as anti
      inflammatory and analgesic agents.
AB  - The ring opening of some phthalimide derivatives with sodium borohydride in
      methanol/water (6:1) afforded the corresponding 2-hydroxymethylbenzamides
      irrespective of the substituents. The most active members of the series evaluated
      for anti-inflammatory and analgesic activities were 2-hydroxymethyl-N-[4-(2
      methoxyphenyl)-piperazin-1-yl]-ethylbenzamide (3d) and 2-hydroxymethyl-N-[4-(2
      methoxyphenyl)-piperazin-1-yl]-propylbenzamide (3e), respectively.

PMID- 17515327
TI  - Synthesis of alkylamides of dipeptides as potential plasmin inhibitors.
AB  - Four dipeptide alkylamides with general formula H-D-Phe-L-Lys-NH-X, where X =
      cyclohexyl, - (CH2)5NH2, -(CH2)2-OH and hexyl were obtained. Effect of these
      compounds on amidolytic and fibrinolytic activity of plasmin was examined.

PMID- 17515328
TI  - Studies on pyrazine derivatives. XLVII. Synthesis and antibacterial activity of
      novel pyrazine derivatives with amidoxime moiety.
AB  - The new pyrazine derivatives exhibiting an antibacterial activity have been
      synthesized. Initial amidoxime 1 was obtained in the reaction of
      pyrazinecarbonitrile with hydroxylamine. Upon treatment of amidoxime with methyl
      iodide O-methyl derivative 2 was formed. Both amidoximes were transformed into
      imidoyl chlorides 3, 4. Then the chloride atom in those derivatives was
      substituted with various secondary amines giving appropriate oximes 5-18 and O
      methyl-oximes 19 and 20. The obtained compounds were tested in vitro for their
      tuberculostatic activity. The inhibiting concentration (MIC) values were within
      25-100 microg/mL. Their activity towards 25 strains of anaerobic and 25 strains
      of aerobic bacteria was also studied. Three compounds exhibited activity against
      both types of bacteria.

PMID- 17515329
TI  - Synthesis of amides of 5-arylidene-2,4-dioxothiazolidine-3-acetic acid with 1,2,4
      triazole system.
AB  - In the reaction of 5-arylidene-2,4-dioxothiazolidine-3-acetic acid chloride with
      1,2,4-triazole, 1,2,4-triazoline-5-one and 1,2,4-triazoline-5-thione, the new
      corresponding 5-arylidene-2,4-dioxothiazolidine-3-acetic acid amides (5-16) were
      obtained. Compounds 6, 14 i 15 were investigated in vitro for their antioxidant
      activity.

PMID- 17515330
TI  - Formualtion and evaluation of floating drug delivery system containing
      clarithromycin for Helicobacter pylori.
AB  - Floating matrix tablets are designed to prolong the gastric residence time after
      oral administration, at a particular site and controlling the release of drug
      especially useful for achieving controlled plasma level as well as improving
      bioavailability. With this objective, floating dosage form containing
      clarithromycin as drug was designed for the treatment of Helicobacter pylori.
      Tablets containing hydroxypropylmethylcellulose (HPMC), drug and different
      additives were compressed using wet granulation and D-optimal design technique.
      The study shows that tablet composition and mechanical strength have great
      influence on the floating properties and drug release. Incorporation of gas
      generating agent together with polymer improved drug release, besides optimal
      floating (floating lag time < 30 s; total floating time > 10 h). The drug release
      was sufficiently sustained (more than 8 h) and anomalous diffusion as well as
      zero-order was confirmed. Optimization of the evaluating parameters with 'design
      expert' software was employed to get final optimized formulation. The optimized
      formulation was obtained using 62.5% clarithromycin, 4.95% HPMC K15M, 18.09% HPMC
      K4M, 12.96% sodium bicarbonate which gave floating lag time < 30 s with a total
      floating time > 10 h, in vitro release profile very near to the target in vitro
      release profile and follows anomalous diffusion as well as zero order pattern of
      release.

PMID- 17515331
TI  - In vitro dissolution kinetic study of theophylline from hydrophilic and
      hydrophobic matrices.
AB  - Oral dosage forms containing 300 mg theophylline in matrix type tablets, were
      prepared by direct compression method using two kinds of matrices,
      glycerylbehenate (hydrophobic), and (hydroxypropyl)methyl cellulose
      (hydrophilic). The in vitro release kinetics of these formulations were studied
      at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The
      kinetics of the dissolution process were studied by analyzing the dissolution
      data using four kinetic equations, the zero-order equation, the first-order
      equation, the Higuchi square root equation and the Hixson-Crowell cube root law.
      The analysis of the dissolution kinetic data for the theophylline preparations in
      this study shows that it follows the first order kinetics and the release process
      involves erosion / diffusion and an alteration in the surface area and diameter
      of the matrix system, as well as in the diffusion path length from the matrix
      drug load during the dissolution process. This relation is best described by the
      use of both the first-order equation and the Hixson-Crowell cube root law.

PMID- 17515332
TI  - Influence of acrylic esters and methacyrlic esters on flotation of pellets and
      release rate of verapamil hydrochloride.
AB  - Eudragit RL (ERL) and Eudragit RS (ERS) are biocompatible cationic copolymers, pH
      independent and insoluble in aqueous environment. In this study drug delivery
      system consisting of a capsule filled with floating pellets with verapamil
      hydrochloride (VH) is proposed. The release of VH in the stomach results in
      better solubility in an acid gastric environment in vivo and may result in
      greater amount of the VH absorbed and its higher concentration in plasma. The
      scope of this study was to investigate the influence of ERL and ERS ratio on VH
      release in 0,1 M HCl from floating coating pellets. The stability of this film
      was also investigated. The ERL film is much more permeable than ERS, and an
      increase of ERL film thickness did not retard the release rate. The combination
      of ERL and ERS are forms of the sustained release film. It was a necessary to add
      the uncoated pellets, which constituted the initial dose. The start of flotation
      depends on permeability of polymeric film, and decreases with addition of ERS.
      There is no change in the start flotation time after 12 months under room
      condition (25 degrees C/60% RH). The drug delivery from uncoated pellets and
      pellets coated with ERL/ERS is stable after 12 months under room condition (25
      degrees C/60% RH).

PMID- 17515333
TI  - Artificial neural networks in the modeling of drugs release profiles from
      hydrodynamically balanced systems.
AB  - Artificial neural networks (ANNs) were used as modeling tools for prediction of
      various drugs release patterns from hydrodynamically balanced systems (HBS)
      composed with Metholose 90SH (hydroxypropylmethylcellulose--HPMC). The objective
      was to provide predictive and data-mining models of analyzed problem. It was
      found that ANNs are capable to accurately predict release patterns of different
      drugs from HBS based on the description of the formulation as well as chemical
      structure of the drug. Overall generalization error RMSE was 8.7 and after
      inclusion of pilot study in learning dataset it decreased to ca. 4.5. Sensitivity
      analysis of ANNs was applied to reduce native input vector from 77 to 7 inputs in
      order to improve the performance of predictive models. Simultaneously, it
      revealed crucial variables governing release of drugs from HBS.

PMID- 17515334
TI  - Radiological reasoning: Right atrial mass.
AB  - OBJECTIVE: An older man with a history of urothelial cancer presented with an
      incidental right atrial mass. Cardiac MRI showed a pedunculated right atrial mass
      that was homogeneous and of intermediate signal intensity on T1- and T2-weighted
      images. No signal drop-out was seen on fat-suppressed images. The mass did not
      exhibit enhancement on the first-pass perfusion and delayed contrast-enhanced
      images. CONCLUSION: A myxoma is the most common benign primary intracavitary
      cardiac mass. Although the MRI features are not pathognomonic, certain features
      such as location, presence of a stalk, and noninfiltrating nature may help to
      distinguish a myxoma from other intracavitary masses such as a thrombus,
      metastases, and primary cardiac malignancy. The final pathologic diagnosis was a
      right atrial myxoma.

PMID- 17515335
TI  - AJR teaching file: Left ventricular mass in a patient with ischemic heart
      disease.

PMID- 17515336
TI  - Approach to dextrocardia in adults: review.
AB  - OBJECTIVE: The educational objectives of this article are to describe an approach
      to analyzing imaging studies in adults with dextrocardia and to present the
      appearances of the most common underlying disorders. Topics reviewed include the
      morphology of the cardiac chambers, the concept of situs, and the relevant
      embryologic principles. The disorders discussed include situs inversus totalis
      (mirror-image dextrocardia), dextroversion, congenitally corrected transposition
      of the great arteries, and polysplenia syndrome. CONCLUSION: In this article we
      describe an approach to dextrocardia in adult patients and illustrate the imaging
      manifestations of the most common underlying disorders.

PMID- 17515337
TI  - Percutaneous arterial embolization in the management of rectus sheath hematoma.
AB  - OBJECTIVE: Spontaneous rectus sheath hematoma can become clinically relevant and
      necessitate hemostatic intervention. The aim of this study was to describe the
      efficacy of percutaneous arterial embolization in the management of this
      condition. CONCLUSION: Selective transcatheter embolization is effective
      hemostatic treatment of patients with large, clinically relevant rectus sheath
      hematoma.

PMID- 17515338
TI  - Gastric linitis plastica from metastatic breast carcinoma: FDG and FES PET
      appearances.

PMID- 17515339
TI  - Spontaneous isolated dissection of the celiac artery: CT findings in adults.
AB  - OBJECTIVE: Our objective was to describe the CT features of spontaneous isolated
      celiac artery dissection in a series of six otherwise healthy patients with acute
      abdominal pain. CONCLUSION: Although once believed rare, isolated spontaneous
      celiac artery dissection should be considered in the diagnosis of acute abdominal
      pain, especially in middle-aged adults.

PMID- 17515340
TI  - MRI of retroperitoneal solitary fibrous tumor in the suprarenal region.

PMID- 17515341
TI  - Sonographic evaluation of venous obstruction in liver transplants.
AB  - OBJECTIVE: The purpose of our study was to identify specific Doppler criteria for
      portal vein and outflow vein (hepatic veins and inferior vena cava) obstruction
      in liver transplants. MATERIALS AND METHODS: A retrospective review was performed
      of Doppler sonographic studies and angiograms in 94 liver transplant cases (72
      whole liver, 22 lobar) with suspected vascular obstruction. The angiograms were
      classified as normal, occluded, or stenosed on the basis of appearance and
      elevated pressure gradient. Sonography was correlated with angiography. The
      following Doppler parameters were evaluated: for the portal vein, peak
      anastomotic velocity and anastomotic-to-preanastomotic velocity ratio; and for
      the outflow veins, venous pulsatility index. Receiver operating characteristic
      curves were constructed and optimum thresholds for stenosis were defined.
      RESULTS: There were 16 cases of portal vein obstruction (11 stenosis, five
      occlusion) and 35 cases of outflow vein obstruction (34 stenoses, one occlusion).
      Mean peak anastomotic velocity in normal portal veins was 58 cm/s, whereas mean
      peak anastomotic velocity in stenosed veins was 155 cm/s (p = 0.0007). Peak
      anastomotic velocity threshold of > 125 cm/s was 73% sensitive and 95% specific
      for stenosis. Mean anastomotic-to-preanastomotic velocity ratio in normal portal
      veins was 1.5, and mean anastomotic-to-preanastomotic velocity ratio in stenosed
      veins was 4.69 (p = 0.001). A 3:1 ratio was 73% sensitive and 100% specific for
      stenosis. Mean venous pulsatility index for normal outflow veins was 0.75, and
      mean venous pulsatility index in stenosed veins was 0.39. A venous pulsatility
      index of < 0.45 was 95.7% specific for stenosis. The areas under the receiver
      operating characteristic curve were 0.83 for peak anastomotic velocity, 0.86 for
      anastomotic-to-preanastomotic velocity ratio, and 0.84 for venous pulsatility
      index, indicating good correlation. CONCLUSION: Peak anastomotic velocity,
      anastomotic-to-preanastomotic velocity ratio, and venous pulsatility index are
      useful parameters for diagnosing venous stenosis in liver transplants.

PMID- 17515342
TI  - B-flow imaging of the hepatic vasculature: correlation with color Doppler
      sonography.
AB  - OBJECTIVE: B-flow imaging is a non-Doppler technology that provides real-time
      imaging of blood flow during gray-scale sonography. The utility of B-flow imaging
      is reflected in numerous publications that describe normal and pathologic
      findings in the carotid arteries and hemodialysis fistulas. However, there is a
      paucity of articles describing B-flow imaging of the abdominopelvic viscera. The
      purpose of this article is to illustrate a spectrum of findings encountered
      during noninvasive flow evaluation of the hepatic vasculature, correlating the
      Doppler sonography and B-flow imaging findings. CONCLUSION: Color and spectral
      Doppler sonography are invaluable for noninvasive evaluation of the hepatic
      vasculature. However, a number of pitfalls and artifacts have been described that
      can cause important pathologic findings to be overlooked or can suggest incorrect
      diagnoses. In our experience, B-flow imaging often correctly displays normal and
      pathological vascular structures for which Doppler sonographic findings have been
      misleading or erroneous.

PMID- 17515343
TI  - Utility of coronary MR angiography in children with Kawasaki disease.
AB  - OBJECTIVE: Although coronary arterial lesions due to Kawasaki disease (KD) should
      be evaluated as early as possible after the acute phase, conventional X-ray
      coronary angiography poses high risks for young children with the disease. The
      use of noninvasive MR coronary angiography is desirable, although it is difficult
      to produce clear images in young children. We developed a method to improve the
      quality of MR coronary angiography in young children. MR coronary angiography
      with vector electrocardiogram gating, real-time navigator-echo, 3D, steady-state
      free precession was performed in 35 children with KD. Many parameters (i.e.,
      field of view, acquisition delay, turbo-field echo-factor, navigator window, and
      resolution) were optimized for each patient. CONCLUSION: Optimization resulted in
      the acquisition of high-resolution and highsignal images of the coronary
      arteries. It remarkably improved not only the quality of the images, but also the
      detection rate of coronary artery segments. MR coronary angiography is a useful
      method for evaluating coronary aneurysms from the early stages of KD, even in
      infants and small children.

PMID- 17515344
TI  - Navigator-gated MR angiography of the renal arteries: a potential screening tool
      for renal artery stenosis.
AB  - OBJECTIVE: The purpose of our study was to determine how well unenhanced
      navigator-gated steady-state free precession (Nav SSFP) MR angiography (MRA)
      performs as a screening test for the detection of renal artery stenosis. SUBJECTS
      AND METHODS: Forty patients referred to rule out renal artery stenosis were
      imaged using an optimized Nav SSFP MRA sequence before conventional contrast
      enhanced MRA (CE-MRA). Two radiologists evaluated Nav SSFP for maximum stenosis
      measurement, and comparison was made with CE-MRA results. RESULTS: Fifteen of the
      40 patients had greater than 50% renal artery stenosis as determined on CE-MRA.
      Sensitivity for detecting renal artery stenosis with Nav SSFP was 100%;
      specificity, 84%; negative predictive value, 100%; and positive predictive value,
      79%. The average mean stenosis difference between Nav SSFP and CE-MRA was 10% +/-
      9%. CONCLUSION: Sensitivity and negative predictive value for the detection of
      renal artery stenosis using Nav SSFP were perfect, with an acceptable specificity
      of 84%. This suggests Nav SSFP is a promising technique for simple unenhanced
      screening for the detection of renal artery stenosis.

PMID- 17515345
TI  - Acquired arteriovenous fistula at an unusual site.

PMID- 17515346
TI  - Cardiac septal aneurysm mimicking pseudomass: appearance on ECG-gated cardiac MRI
      and MDCT.
AB  - OBJECTIVE: Cardiac septal aneurysms in adults are diagnosed when the interatrial
      or interventricular septal membrane deviates more than 10-15 mm to either side in
      the cardiac chamber. Routine non-ECG-gated chest CT does not have sufficient
      temporal and spatial resolution for adequate characterization of such an entity.
      We report the imaging findings of cardiac septal aneurysms depicted in two
      patients with ECG-gated cardiac MRI and in a third with ECG-gated cardiac 64
      MDCT. Each aneurysm was initially believed to be a cardiac tumor on the basis of
      the appearance on non-ECG-gated chest CT or MRI. CONCLUSION: Nonopacified blood
      can fill a cardiac septal aneurysm and mimic a pseudomass. It is important that
      radiologists recognize such an entity on chest CT and MRI because of the
      association with intracardiac shunting and stroke and to avoid misdiagnosis of an
      aneurysm as a cardiac tumor.

PMID- 17515347
TI  - Follicular dendritic cell sarcoma of the mediastinum.

PMID- 17515348
TI  - CT findings of varicella pneumonia after lung transplantation.

PMID- 17515349
TI  - Intrathecal administration of gadopentetate dimeglumine for MR cisternography of
      nasoethmoidal CSF fistula.
AB  - OBJECTIVE: Accurate diagnosis and localization of dural defects associated with
      CSF fistulas are difficult and often involve multiple imaging studies performed
      at the appropriate clinical moment. Our purpose was to assess the utility of
      intrathecal administration of gadopentetate dimeglumine for MR cisternography of
      patients with CSF fistula suspected clinically to arise from defects in the
      nasoethmoidal regions. CONCLUSION: MR cisternography was useful for evaluating
      patients with rhinorrhea and suspected CSF fistula. It depicted the fistula site
      in most patients. No adverse effects were found in any patient.

PMID- 17515350
TI  - Shareware program for nuclear medicine and PET/CT PACS display and processing.
AB  - OBJECTIVE: Many of the functions necessary for imaging and analyzing nuclear
      medicine studies are not available on radiology PACS. Over the past 20 years, we
      have developed a user-friendly, easily installed software package for nuclear
      medicine study analysis, display, Web access, and database storage and an
      integrated display for fused PET/CT. We are making this software available as
      free shareware that can be used without a license on any PC. The software package
      was developed as a cooperative effort between house and attending staff and our
      nuclear medicine programmer. Particular emphasis was put on making functions
      intuitive and user friendly. CONCLUSION: A shareware nuclear medicine PACS
      software package including a display for fused PET/CT studies has been developed,
      extensively clinically tested, and is freely available on the Internet.

PMID- 17515351
TI  - Dynamic contrast-enhanced CT of renal cell carcinoma for evaluation of tumor
      vascularity: analysis of single-phase or multiphase scanning.

PMID- 17515352
TI  - Does size matter? Likelihood of cancer in MRI-detected lesions less than 5 mm.

PMID- 17515353
TI  - Isolation of radiologists: who is to blame and what needs to be done?

PMID- 17515354
TI  - Specificity gains at the expense of sensitivity and vice versa.

PMID- 17515355
TI  - Image-annotated radiographic reports.

PMID- 17515356
TI  - Radiofrequency ablation of osteoid osteoma with cooled probes and impedance
      control energy delivery.

PMID- 17515357
TI  - Nephrogenic systemic fibrosis and nonionic linear chelates.

PMID- 17515358
TI  - Gadolinium-associated nephrogenic systemic fibrosis: double dose, not single
      dose.

PMID- 17515359
TI  - Gadodiamide-associated nephrogenic systemic fibrosis.

PMID- 17515360
TI  - Diagnostic radiology and the new Congress: where are the health priorities?

PMID- 17515361
TI  - "MRI in the detection of malignant infiltration of bone marrow"--a commentary.

PMID- 17515362
TI  - Commentary on "ACR guidance document for safe MR practices: 2007".

PMID- 17515363
TI  - ACR guidance document for safe MR practices: 2007.

PMID- 17515364
TI  - GoldMiner: a radiology image search engine.
AB  - OBJECTIVE: We sought to create an Internet-based search engine to retrieve images
      from a large collection of figures published in peer-reviewed journals.
      CONCLUSION: The GoldMiner search engine provides easy, rapid access to a large
      library of images and their associated text, and it is freely available for use
      on the Internet.

PMID- 17515365
TI  - CT-guided interventional procedures without CT fluoroscopy assistance: patient
      effective dose and absorbed dose considerations.
AB  - OBJECTIVE: The purpose of this study was to determine patient effective dose (E)
      and peak absorbed dose to the skin of the patient from various CT-guided
      interventional procedures performed without CT fluoroscopy assistance. MATERIALS
      AND METHODS: In total, 49 interventions were retrospectively studied: 14
      biopsies, 14 radiofrequency ablations, 14 abscess drainages, and seven
      nephrostomies. CT images were acquired from the department's PACS system and
      reviewed to record the scan parameters of each slice. Entrance surface dose and E
      were estimated using the Impactscan database and the related Monte Carlo
      conversion coefficients. RESULTS: Median values of E for biopsies, radiofrequency
      ablations, abscess drainages, and nephrostomies were 23, 35.3, 16.2, and 11.5
      mSv, respectively. Respective ranges were 5.8-46.6, 18.4-57.2, 10.9-31.5, and 5.1
      32.7 mSv. The corresponding median values and ranges for the peak absorbed dose
      were 281, 557, 155, and 145 mGy and 133-982, 147-699, 94-315, and 75-297 mGy. The
      diagnostic scans obtained before the interventions were responsible for 63%, 33%
      40%, and 51% of E, respectively. The largest contribution to the peak absorbed
      dose was due to positioning of the tissue acquisition biopsy gun in biopsies
      (48%), the radiofrequency needle in ablations (57%), and the catheter in abscess
      drainages (41%) and nephrostomies (49%). CONCLUSION: For the CT interventions
      studied, and especially for biopsies and radiofrequency ablations, patient
      effective doses were considerably high. Maximum peak absorbed dose observed was
      about 1 Gy, considerably lower than the threshold for deterministic effects (2
      Gy).

PMID- 17515366
TI  - Multiple-electrode radiofrequency ablation of hepatic malignancies: initial
      clinical experience.
AB  - OBJECTIVE: The objective of our study was to retrospectively analyze our initial
      clinical experience with percutaneous multiple-electrode radiofrequency ablation
      and evaluate its safety and efficacy for treating hepatic malignancies. MATERIALS
      AND METHODS: Thirty-eight malignant hepatic tumors (mean diameter, 2.7 cm; range,
      0.7-10.0 cm) in 23 patients (12 men and 11 women; mean age, 65 years; range, 40
      84 years) were treated in 26 radiofrequency ablation sessions with an impedance
      based multiple-electrode system. One, two, or three (mean, 2.4) 17-gauge
      electrodes were placed, and tumors were ablated using a combination of CT and
      sonography for guidance and monitoring. Electrodes were placed in close proximity
      (mean spacing: two electrodes, 1.0 cm; three electrodes, 1.4 cm) to treat large
      tumors or were used independently to treat several tumors simultaneously.
      Contrast-enhanced CT scans were obtained immediately after ablation to determine
      technical success and evaluate for complications. Follow-up CT scans at 1, 3, 6,
      9, and 12 months (mean, 4 months) after ablation were obtained to assess for
      tumor progression and new metastases. RESULTS: Local control was achieved in 37
      of 38 tumors, 34 of which were treated in one session. Ablations created with
      closely spaced electrodes had a mean diameter of 4.9 cm. The total ablation time
      was reduced by approximately 54% compared with an equivalent number of ablations
      performed with a single-electrode system (1,014 vs 2,196 minutes). Three
      complications occurred: one death from a presumed postprocedure pulmonary
      embolus, one pneumothorax, and one asymptomatic perihepatic hemorrhage.
      CONCLUSION: Multiple-electrode radiofrequency ablation appears to be a safe and
      effective means of achieving local control in large or multiple hepatic
      malignancies at short-term follow-up.

PMID- 17515367
TI  - Stent collapse as a delayed complication of placement of a covered gastroduodenal
      stent.
AB  - OBJECTIVE: The purpose of this study was retrospective evaluation of the
      incidence, predictive factors, and interventional management of stent collapse
      after placement of a covered metallic stent in patients with obstruction of the
      gastric outlet or duodenum due to malignant disease. MATERIALS AND METHODS: Among
      259 patients with symptomatic malignant gastroduodenal obstruction successfully
      treated with stent placement, stent collapse occurred in 12 (4.6%) of the
      patients 34-270 days (mean, 101.8 days) after stent placement. Multivariate
      analysis was performed to evaluate factors predictive of stent collapse.
      Interventional management of stent collapse also was evaluated. RESULTS:
      Multivariate analysis showed that presence of the stent in the peripyloric region
      (odds ratio, 27.745; p = 0.036), longer survival time (odds ratio, 1.016; p <
      0.001), and absence of chemotherapy after stent placement (odds ratio, 31.661; p
      = 0.048) were independent predictors of stent collapse. Eleven patients with
      stent collapse were successfully treated with placement of a second bare stent.
      The twelfth patient refused further treatment. CONCLUSION: Stent collapse is an
      uncommon delayed complication of placement of covered metallic stents in patients
      with malignant gastroduodenal obstruction. Collapse occurs most commonly in the
      peripyloric region, in patients with longer survival times, and in patients who
      do not undergo chemotherapy after stent placement. Stent collapse can be managed
      by coaxial placement of a second bare stent into the collapsed stent.

PMID- 17515368
TI  - CT-guided biopsy for the diagnosis of renal tumors before treatment with
      percutaneous ablation.
AB  - OBJECTIVE: Percutaneous thermal ablation is an emerging technique in the
      management of renal cell carcinoma (RCC), with greatest efficacy in tumors < or =
      3 cm. The purpose of this retrospective study was to evaluate the role and
      utility of pretreatment CT-guided biopsy in patients referred for percutaneous
      thermal ablation of renal tumors. CONCLUSION: Less than 5% of samples in our
      study were benign, and 11.8% were nondiagnostic. Biopsy in smaller lesions was
      less accurate; therefore biopsy is less useful for these renal lesions. Because
      fine-needle aspiration (FNA) has higher sensitivity than core biopsy, an
      appropriate algorithm may be to begin with FNA and reserve core biopsy for cases
      in which an onsite cytotechnologist is unavailable or deems the sample of
      inadequate cellularity.

PMID- 17515369
TI  - Establishing an outpatient clinic for minimally invasive vein care.
AB  - OBJECTIVE: Minimally invasive vein care procedures are less invasive than surgery
      and have a lower complication rate, are well tolerated by patients, and have good
      cosmetic results. Because radiologists have expertise in imaging-guided
      procedures, offering minimally invasive vein care is a logical step. CONCLUSION:
      Starting an effective outpatient vein care clinic involves decisions about space,
      equipment, and advertising. With proper staffing and rapport with patients and
      referring physicians, a varicose vein practice can be a profitable adjunct to any
      radiology practice.

PMID- 17515370
TI  - Characterization of musculoskeletal lesions on 3-T proton MR spectroscopy.
AB  - OBJECTIVE: The purpose of our study was to determine the feasibility and value of
      proton MR spectroscopy at 3 T for characterizing musculoskeletal tumors. SUBJECTS
      AND METHODS: At 3 T, 18 patients with musculoskeletal lesions (four
      histologically proven to be malignant, 14 proven benign histologically or at
      clinical follow-up) underwent 23 MR spectroscopy studies, 20 with a single-voxel
      technique and three with a multivoxel technique. Seventeen patients were imaged
      with a surface coil and six with a body coil. Choline signal (3.2 ppm) was
      measured in each voxel and expressed relative to background noise as signal-to
      noise ratio (SNR). Choline SNRs of malignant tumors and benign lesions were
      compared. RESULTS: Diagnostic spectra were obtained in 20 of 23 lesions. For
      malignant lesions (osteosarcoma with two MR spectroscopy sites, metastasis, grade
      1 sarcoma), choline SNRs were 5.2 and 4.2 (performed with body coil) and 4.8 and
      18.7 (performed with surface coil), respectively. For benign lesions
      (neurofibroma, two stress reactions, bone cyst, hemangioma, lipoma, Baker cyst),
      choline SNR was 6.3 (with surface coil), 5.5 (with surface coil), and not
      detected for five cases. Seven postoperative patients with myocutaneous flaps
      showed either the typical spectrum of muscle or negligible choline. Only a water
      peak existed in a bone cyst and a significant lipid peak in a lipoma. Choline
      SNRs were different for malignant and benign lesions (11.7 vs 2.3, p = 0.04, as
      performed with a surface coil). CONCLUSION: At 3 T, both single-voxel and
      multivoxel MR spectroscopy are feasible. Proton MR spectroscopy is a potential
      noninvasive tool for characterizing lesion composition and malignant activity.

PMID- 17515371
TI  - Semiquantitative assessment of skeletal response to enzyme replacement therapy
      for Gaucher's disease using the bone marrow burden score.
AB  - OBJECTIVE: The purpose of this study was to evaluate the use of a recently
      described assessment tool to quantify bone marrow response to enzyme replacement
      therapy in a cohort of adult patients with type 1 Gaucher's disease. MATERIALS
      AND METHODS: Serial MR images of the femurs, lumbar spine, or both of 57 subjects
      with a diagnosis of Gaucher's disease, 44 of whom were being treated with enzyme
      replacement therapy, were evaluated by two musculoskeletal radiologists using the
      bone marrow burden (BMB) scoring system. This system gives a score out of a
      possible 8 for the lumbar spine and a score out of a possible 8 for the femurs,
      so the total BMB score is out of 16. RESULTS: The mean total BMB scores at
      baseline and final measurement were 13 (95% CI, 12.0-13.8) and 6.5 (95% CI, 5.2
      7.9), respectively. Total BMB scores improved by 2-12 points (mean, 6.3 points)
      for 15 subjects in whom total BMB scores obtained before enzyme replacement
      therapy and at least one time point after commencement of therapy were available.
      In 39 subjects for whom only baseline and final femoral BMB scores were
      available, 24 subjects (62%, 95% CI, 47-76%) improved by 2 or more points while
      on enzyme replacement therapy. In 24 subjects for whom only baseline and final
      lumbar BMB scores were available, the BMB score in 16 subjects (67%, 95% CI, 48
      85%) improved by 2 or more points. CONCLUSION: The use of the BMB score enabled
      semiquantitative assessment of bone marrow response to enzyme replacement therapy
      in adult patients with type 1 Gaucher's disease in Australia. The ability to
      assess therapy response will facilitate the tailoring of dosage regimens in the
      future.

PMID- 17515372
TI  - Imaging-guided bone biopsy for osteomyelitis: are there factors associated with
      positive or negative cultures?
AB  - OBJECTIVE: The objective of our study was to identify the clinical and technical
      factors associated with positive or negative culture results in histologically
      positive cases of osteomyelitis obtained from imaging-guided bone biopsies.
      MATERIALS AND METHODS: A retrospective review was performed of 800 consecutive
      patients undergoing imaging-guided core bone biopsies at two institutions.
      Seventy-five biopsies were performed for suspected osteomyelitis and 41 patients
      had histologically proven osteomyelitis. A chart review was performed to
      determine whether the following factors affected the culture result: histologic
      type of osteomyelitis, antibiotic therapy before biopsy, fever (temperature > or
      = 38.0 degrees C), elevated WBC count (> or = 10 x 10(3) microL), elevated
      erythrocyte sedimentation rate (ESR) (> or = 10 mm/h), elevated C-reactive
      protein value (CRP) (> or = 6 mg/L), the size of the biopsy needle, and the
      amount of purulent fluid obtained at biopsy. RESULTS: Of the 41 cases of
      osteomyelitis, 14 (34%) had positive cultures. Eighteen (44%) of 41 cases were
      chronic osteomyelitis. Seventeen (41%) of 41 patients received antibiotics before
      biopsy, seven (17%) were febrile, five (12%) had an elevated WBC count, 16 (39%)
      had an elevated ESR, and six (15%) had an elevated CRP value. The biopsy needle
      size ranged from 11- to 18-gauge. These factors did not have any significant
      association with positive or negative culture results. Purulent fluid was
      aspirated in 10 (24%) of the 41 cases. In six (15%) of the cases, > or = 2 mL of
      purulent fluid was aspirated and five (83%) of the six cases were associated with
      positive culture (p = 0.02). CONCLUSION: The rate of positive culture results in
      histologically proven cases of osteomyelitis obtained from imaging-guided bone
      biopsies is low. Aspirating > or = 2 mL of purulent fluid is associated with a
      significantly higher rate of positive cultures.

PMID- 17515373
TI  - Treatment of Morton's neuroma with alcohol injection under sonographic guidance:
      follow-up of 101 cases.
AB  - OBJECTIVE: Morton's neuroma is a common cause of forefoot pain. For this study,
      we assessed the efficacy of a series of sonographically guided alcohol injections
      into the lesion. SUBJECTS AND METHODS: One hundred one consecutive patients with
      Morton's neuroma were included in this prospective series. An average of 4.1
      treatments per person were administered, and follow-up images were obtained at a
      mean of 21.1 months after the last treatment (range, 13-34 months). RESULTS:
      Technical success was 100%. Partial or total symptom improvement was reported by
      94% of the patients, with 84% becoming totally pain-free. The median visual
      assessed pain score decreased from 8 before treatment to 0 after treatment (p <
      0.001). Transitory increased local pain occurred in 17 cases (16.8%). There were
      no major complications. Thirty patients underwent sonography at 6 months after
      the last injection and showed a 30% decrease in the size of the neuroma.
      CONCLUSION: We conclude that alcohol injection of Morton's neuroma has a high
      success rate and is well tolerated. The results are at least comparable to
      surgery, but alcohol injection is associated with less morbidity and surgical
      management may be reserved for nonresponders.

PMID- 17515374
TI  - Femoroacetabular impingement: radiographic diagnosis--what the radiologist should
      know.
AB  - OBJECTIVE: The purpose of this article is to show the important radiographic
      criteria that indicate the two types of femoroacetabular impingement: pincer and
      cam impingement. In addition, potential pitfalls in pelvic imaging concerning
      femoroacetabular impingement are shown. CONCLUSION: Femoroacetabular impingement
      is a major cause for early "primary" osteoarthritis of the hip. It can easily be
      recognized on conventional radiographs of the pelvis and the proximal femur.

PMID- 17515375
TI  - Perspectives on the influence of "Arthrotomography of the temporomandibular
      joint".

PMID- 17515376
TI  - Frequency and extent of uterine perfusion via ovarian arteries observed during
      uterine artery embolization for leiomyomas.
AB  - OBJECTIVE: The objective of our study was to evaluate the frequency and extent of
      residual uterine perfusion via the ovarian arteries after bilateral uterine
      artery embolization (UAE) for the treatment of symptomatic uterine leiomyomas.
      MATERIALS AND METHODS: One hundred forty-five consecutive patients who underwent
      UAE were retrospectively evaluated for blood supply to the uterus via the ovarian
      arteries after UAE. After completion of UAE, uterine supply from the ovarian
      arteries was assessed by performing abdominal aortography in all patients.
      Selective ovarian arteriography, in addition, was performed in some patients. The
      criteria used to characterize ovarian artery perfusion as seen on the aortograms
      were vessel size compared with a 5-French catheter and visualization and extent
      of flow. When the ovarian arteries visibly supplied uterine tissue, a
      quantification system was applied as follows: the uterus was divided in 24
      segments on the basis of a clock model that was superimposed over the uterine
      territory in the anteroposterior projection. Depending on its distance from the
      midpoint of the clock, perfusion segments were labeled as central, middle,
      distal, or peripheral for each hour of the clock resulting in a total of 24 (12 x
      2) potential segments of residually perfused uterine tissue via the ovarian
      arteries. RESULTS: Two hundred ninety ovarian arteries were evaluated on
      aortography; of these, 202 (70%) were not seen during aortography. Of the
      visualized ovarian arteries (n = 88), 52% (46/88) were smaller than, 25% (22/88)
      were equal to, and 23% (20/88) were larger than the diameter of a 5-French
      catheter. The aortogram revealed that 61% (54/88) of the ovarian arteries
      extended into the pelvis, whereas 38% (33/88 [one missing data point]) did not.
      Selective injections were performed in 54 ovarian arteries. Of these, 69% (37/54)
      of the ovarian arteries had residual fibroid perfusion from the ovarian arteries
      after UAE (10 left-sided, 15 right-sided, six bilateral = 37 ovarian arteries).
      Residual fibroid perfusion was more likely in large ovarian arteries,
      particularly those with rapid flow visualized extending into the pelvis. The
      perfusion scores ranged from one to 18 segments (< 6 segments, n = 21 ovarian
      arteries; 6-12 segments, n = 12; > 12 segments, n = 4). Direct communication with
      the uterine arteries was seen in 20 ovarian arteries, 40% (8/20) of which did not
      show any uterine or fibroid perfusion, suggesting that fibroid flow had been
      occluded by UAE. CONCLUSION: Based on aortography, the presence of residual
      fibroid perfusion is more likely if the ovarian arteries are large, have rapid
      flow, or have flow that extends into the pelvis. Selective ovarian artery
      evaluation may be indicated in these cases to determine the extent of residual
      fibroid perfusion.

PMID- 17515377
TI  - Detection of the gonadal veins in the diagnosis of transposed ovaries in patients
      with cervical carcinoma: a useful sign on MDCT.
AB  - OBJECTIVE: The purpose of our study was to evaluate the detectability of the
      gonadal vein of transposed ovaries in patients with uterine cervical cancer on
      MDCT. CONCLUSION: Gonadal veins and surgical clips of transposed ovaries can be
      shown with high consistency on MDCT. Tracking the gonadal veins and detecting the
      surgical clips may prevent the transposed ovaries from being misinterpreted as
      peritoneal implants.

PMID- 17515378
TI  - High-resolution MRI in detecting subareolar breast abscess.
AB  - OBJECTIVE: Because subareolar breast abscess has a high recurrence rate, a more
      effective imaging technique is needed to comprehensively visualize the lesions
      and guide surgery. We performed a high-resolution MRI technique using a
      microscopy coil to reveal the characteristics and extent of subareolar breast
      abscess. CONCLUSION: High-resolution MRI has potential diagnostic value in
      subareolar breast abscess. This technique can be used to guide surgery with the
      aim of reducing the recurrence rate.

PMID- 17515379
TI  - Nonnecrotizing systemic granulomatous panniculitis involving the breast: imaging
      correlation of a breast cancer mimicker.

PMID- 17515380
TI  - MRI of malignant neoplasms of the uterine corpus and cervix.
AB  - OBJECTIVE: In this article, we review the role of MRI in the imaging of malignant
      neoplasms of the uterine corpus and cervix, describing its role in staging,
      treatment planning, and follow-up. CONCLUSION: MRI is not officially incorporated
      in the International Federation of Gynecology and Obstetrics (FIGO) staging
      system, but is already widely accepted as the most reliable imaging technique for
      the diagnosis, staging, treatment planning, and follow-up of both endometrial and
      cervical cancer. MRI protocols need to be optimized to obtain the best results
      and avoid pitfalls.

PMID- 17515381
TI  - Imaging findings of leukemic involvement of the pancreaticobiliary system in
      adults.
AB  - OBJECTIVE: Our objective was to review the imaging findings of patients with
      leukemic involvement of the pancreaticobiliary system in adults. CONCLUSION:
      Pancreatic myeloid and lymphoid leukemia show single or multiple mass lesions of
      homogeneous low attenuation and poor contrast enhancement on CT that is
      radiographically indistinguishable from that of pancreatic lymphoma. Although
      more cases are needed for confirmation, leukemic infiltration of the biliary
      tract is characterized by wall thickening of the bile duct with minimal contrast
      enhancement--a feature that may be helpful in differentiating it from
      infiltrating hilar or extrahepatic cholangiocarcinoma.

PMID- 17515382
TI  - Parasitic diseases of the biliary tract.
AB  - OBJECTIVE: Parasites residing in the biliary tree include Clonorchis sinensis,
      Opisthorchis viverrini, Opisthorchis felineus, and Fasciola hepatica. They are
      willowy, leaf-like, flat flukes dwelling in the bile ducts and gallbladder. Human
      ascarides, Ascaris lumbricoides, dwelling in the small intestine, inadvertently
      migrate into the bile ducts and cause biliary obstruction. The purpose of this
      article is to illustrate typical imaging findings of liver fluke infection and
      biliary ascariasis. CONCLUSION: Adult flukes of Clonorchis and Opisthorchis
      measure 8-15 mm and adult flukes of Fasciola measure 20-40 mm in length. The
      presence of flukes in the bile ducts causes dilatation of the bile ducts, varying
      degrees of chronic inflammation followed by adenomatous hyperplasia, and bile
      duct wall thickening. Imaging findings of clonorchiasis and opisthorchiasis
      include visualization of adult flukes in the bile ducts and gallbladder, diffuse
      dilatation of the peripheral small intrahepatic bile ducts with no or minimal
      dilatation of the large bile ducts, and thickening of the bile duct wall. In
      biliary fascioliasis and ascariasis, adult worms are visualized in the dilated
      bile ducts and gallbladder.

PMID- 17515383
TI  - Pneumatosis intestinalis in the adult: benign to life-threatening causes.
AB  - OBJECTIVE: The frequency of detection of pneumatosis intestinalis (PI) appears to
      be increasing. This increase may be the result of increased CT use. New
      medications and surgical procedures have been reported to be associated with an
      increase in the incidence of PI. The purpose of this review is to provide an
      update on the imaging features and clinical conditions associated with PI.
      CONCLUSION: This article illustrates the imaging findings of PI due to benign and
      life-threatening causes, with emphasis placed on describing newly associated
      conditions and also the imaging appearance on CT.

PMID- 17515384
TI  - Primary hepatic angiosarcoma on coregistered FDG PET and CT images.

PMID- 17515385
TI  - Effect of radiofrequency ablation of renal tumors on renal function in patients
      with a solitary kidney.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect on renal function
      of percutaneous radiofrequency ablation of renal tumors in patients with a
      solitary kidney. CONCLUSION: Ablation resulted in complete tumor eradication, and
      there were no serious complications. Percutaneous radiofrequency ablation of
      renal tumors resulted in a 16% increase in serum creatinine concentration and a
      13% decrease in creatinine clearance in patients with one kidney. These results
      are comparable with those of surgical resection of tumors in this group of
      patients.

PMID- 17515386
TI  - Diffusion-weighted MRI in the body: applications and challenges in oncology.
AB  - OBJECTIVE: In this article, we present the basic principles of diffusion-weighted
      imaging (DWI) that can aid radiologists in the qualitative and quantitative
      interpretation of DW images. However, a detailed discussion of the physics of DWI
      is beyond the scope of this article. A short discussion ensues on the technical
      aspects of performing DWI in the body. The emerging applications of DWI for tumor
      detection, tumor characterization, distinguishing tumor tissue from nontumor
      tissue, and monitoring and predicting treatment response are highlighted. The
      challenges to widespread adoption of the technique for cancer imaging in the body
      are discussed. CONCLUSION: DWI derives its image contrast from differences in the
      motion of water molecules between tissues. Such imaging can be performed quickly
      without the need for the administration of exogenous contrast medium. The
      technique yields qualitative and quantitative information that reflects changes
      at a cellular level and provides unique insights about tumor cellularity and the
      integrity of cell membranes. Recent advances enable the technique to be widely
      applied for tumor evaluation in the abdomen and pelvis and have led to the
      development of whole-body DWI.

PMID- 17515387
TI  - Extracorporeal membrane oxygenation in infants with congenital diaphragmatic
      hernia: follow-up MRI evaluating carotid artery reocclusion and neurologic
      outcome.
AB  - OBJECTIVE: The purpose of our study was to prospectively assess, using MRI and MR
      angiography, the cerebral and vascular status of 2-year-old children with
      congenital diaphragmatic hernia (CDH) in whom carotid artery reconstruction was
      performed after neonatal extra-corporeal membrane oxygenation (ECMO) therapy and
      to compare the neurologic development of children with vascular reocclusion with
      that of CDH children with successful repair and with non-ECMO controls. SUBJECTS
      AND METHODS: A total of 30 infants (17 boys, 13 girls; 2 +/- 0.26 years) were
      included. Of these, 18 (60%) infants received arteriovenous ECMO therapy with
      subsequent reconstruction of the right common carotid artery (RCCA). Two years
      postoperatively, the children were examined with cerebral MRI, including 3D time
      of-flight and contrast-enhanced 3D MR angiography of the intra- and extracranial
      brain-supplying arteries. The pathologic findings were analyzed for the ability
      to predict impaired neurologic development. RESULTS: The RCCA was occluded or
      highly stenotic in 13 (72%) of 18 children. All infants showed intra- and
      extracranial collaterals and a patent internal carotid artery. The average
      duration of ECMO was not longer than in cases of successful reconstruction (p =
      1). The ECMO group showed a significantly greater incidence of cerebral injuries
      (p = 0.007) but no relevant impairment in neurologic development compared with
      controls (p = 0.26). Unsuccessful RCCA repair had no predictive value for a poor
      neurologic outcome (p = 1). CONCLUSION: The outcome of RCCA repair after ECMO is
      possibly poorer than expected, with vascular occlusion or high-grade stenosis
      occurring in almost three quarters of patients. Although reocclusion of the RCCA
      does not increase the risk for cerebral lesions or an impaired neurologic
      development during the first 2 years postoperatively, the overall benefit of RCCA
      repair remains doubtful, and the potential long-term risk arising from these
      plaques has yet to be assessed.

PMID- 17515388
TI  - Incidence and severity of acute allergic-like reactions to i.v. nonionic
      iodinated contrast material in children.
AB  - OBJECTIVE: The purpose of this study was to evaluate the incidence and severity
      of acute allergic-like reactions related to i.v. administration of low-osmolality
      nonionic iodinated contrast material in children. MATERIALS AND METHODS:
      Department of radiology contrast material reaction forms involving pediatric
      (younger than 19 years) imaging examinations performed from January 1, 1999,
      through June 30, 2006, were retrospectively evaluated for type of acute allergic
      like reaction, severity of reaction, and patient outcome. The electronic medical
      record was reviewed for pertinent medical history related to each acute reaction,
      including previous contrast material reaction, premedication before
      administration of i.v. iodinated contrast material, previous allergic-like
      reaction to substances other than contrast material, and history of asthma.
      RESULTS: In our department during the time period specified, 11,306 pediatric
      i.v. administrations of low-osmolality nonionic iodinated contrast material were
      performed. Acute allergic-like reactions to the contrast material were documented
      in 20 (0.18%) of the patients. Sixteen (80%) of the acute allergic-like reactions
      were categorized as mild, one (5%) as moderate, and three (15%) as severe. No
      deaths were attributed to i.v. nonionic iodinated contrast material. Six (30%) of
      the patients had a history of allergic-like reaction, including two patients who
      had a history of reaction to iodinated contrast material. Five (25%) of the
      patients had a history of asthma. CONCLUSION: Acute allergic-like reactions to
      i.v. administration of low-osmolality nonionic iodinated contrast material in
      children are rare. As in the adult population, most pediatric reactions are mild;
      however, severe reactions do occur.

PMID- 17515389
TI  - MOSFET dosimetry for radiation dose assessment of bismuth shielding of the eye in
      children.
AB  - OBJECTIVE: The purpose of our study was to measure radiation dose to the orbit
      during pediatric cranial CT with and without bismuth shielding using a novel
      dosimetry system. Cranial CT was performed on a pediatric anthropomorphic
      phantom, with and without bismuth eye shields. A solid-state metal oxide
      semiconductor field effect transistor (MOSFET) dosimeter was used to obtain real
      time dose measurements. CONCLUSION: Bismuth shielding reduced radiation dose to
      the eye by up to 42%; shield artifact fell outside the diagnostic area of
      interest.

PMID- 17515390
TI  - MDCT angiography of the renal arteries in patients with atherosclerotic renal
      artery stenosis: implications for renal artery stenting with distal protection.
AB  - OBJECTIVE: Use of distal protection in renal artery stenting entails overcoming
      challenges unique to renal artery anatomy. We used 3D image reconstruction to
      review high-spatial-resolution MDCT angiographic data to better characterize the
      anatomy of stenotic renal arteries. MATERIALS AND METHODS: A total of 218
      abdominal MDCT angiograms from a single tertiary care referral center were
      reviewed. The subjects were 108 patients who had 127 arteries with more than 50%
      ostial atherosclerotic renal artery stenosis. Vessel analysis software was used
      to measure renal artery length, cross-sectional area, and maximum diameter.
      Differences between mean values for women and men and for left and right renal
      arteries were measured with a two-tailed Student's t test. RESULTS: Significant
      differences for men and women were found in average maximum cross-sectional area
      distal to the point of stenosis (0.3 +/- 0.19 vs 0.23 +/- 0.09 cm2, p = 0.006)
      and the corresponding maximum diameter (6.9 +/- 1.7 vs 6.1 +/- 1.1 cm2, p =
      0.003). Average lengths of the main renal artery did not differ significantly for
      men and women. Differences for the left and right main renal arteries were found
      in minimum area (i.e., area of maximum stenosis, 0.08 +/- 0.04 vs 0.06 +/- 0.03
      cm2, p = 0.03), area proximal to the bifurcation (0.26 +/- 0.11 cm2 vs 0.23 +/-
      0.07 cm2, p = 0.02), and length (38.5 +/- 12.6 vs 48.7 +/- 16.2 mm, p = 0.0002).
      CONCLUSION: Significant anatomic differences exist between the left and right
      renal arteries, between the renal arteries in men and those in women, and from
      one person to the next. Many of these differences are relevant to the design and
      use of distal protection devices in stenting of the renal arteries.

PMID- 17515391
TI  - Gradual pulmonary artery enhancement: new sign of septal defects on CT.
AB  - OBJECTIVE: Hemodynamic information observed on serial images obtained with bolus
      tracking might help in diagnosing septal defects on CT. Our purpose was to
      qualitatively and quantitatively examine a new sign called gradual pulmonary
      artery enhancement. CONCLUSION: Gradual pulmonary artery enhancement is a newly
      recognized CT sign that may be helpful in evaluating septal defects.

PMID- 17515392
TI  - Normal and variant coronary arterial and venous anatomy on high-resolution CT
      angiography.
AB  - OBJECTIVE: This article displays the normal and variant anatomy of the coronary
      arteries and subjacent cardiac veins using a high-resolution 64-MDCT scanner.
      CONCLUSION: Knowledge of the anatomy of the coronary arteries and subjacent
      cardiac veins as displayed with maximum intensity and volume-rendered projections
      is important for correct image interpretation of coronary CT angiography
      examinations.

PMID- 17515393
TI  - Non-ischemic causes of delayed myocardial hyperenhancement on MRI.
AB  - OBJECTIVE: Delayed contrast-enhanced cardiac MRI has been used to evaluate
      myocardial viability in ischemic heart disease (IHD). However, it can also be
      used in the assessment of non-ischemic cardiac diseases. CONCLUSION: We
      illustrate a number of non-ischemic cardiac conditions and describe how they can
      be differentiated from IHD.

PMID- 17515394
TI  - Characterization of the relation between CT technical parameters and accuracy of
      quantification of lung attenuation on quantitative chest CT.
AB  - OBJECTIVE: The purpose of this study was to assess the compromise between CT
      technical parameters and the accuracy of CT quantification of lung attenuation.
      MATERIALS AND METHODS: Materials that simulate water (0 H), healthy lung (-650
      H), borderline emphysematous lung (-820 H), and severely emphysematous lung (
      1,000 H) were placed at both the base and the apex of the lung of an
      anthropomorphic phantom and outside the phantom. Transaxial CT images through the
      samples were obtained while the effective tube current was varied from 440 to 10
      mAs, kilovoltage from 140 to 80 kVp, and slice thickness from 0.625 to 10 mm.
      Mean +/- SD attenuation within the samples and the standard quantitative chest CT
      measurements, the percentage of pixels with attenuation less than -910 H and 15th
      percentile of attenuation, were computed. RESULTS: Outside the phantom,
      variations in CT parameters produced less than 2.0% error in all measurements.
      Within the anthropomorphic phantom at 30 mAs, error in measurements was much
      larger, ranging from zero to 200%. Below approximately 80 mAs, mean attenuation
      became increasingly biased. The effects were most pronounced at the apex of the
      lungs. Mean attenuation of the borderline emphysematous sample of apex decreased
      55 H as the tube current was decreased from 300 to 30 mAs. Both the 15th
      percentile of attenuation and percentage of pixels with less than -910 H
      attenuation were more sensitive to variations in effective tube current than was
      mean attenuation. For example, the -820 H sample should have 0% of pixels less
      than -910 H, which was true at 400 mA. At 30 mA in the lung apex, however, the
      measurement was highly inaccurate, 51% of pixels being below this value.
      Decreased kilovoltage and slice thickness had analogous, but lesser, effects.
      CONCLUSION: The accuracy of quantitative chest CT is determined by the CT
      acquisition parameters. There can be significant decreases in accuracy at less
      than 80 mAs for thin slices in an anthropomorphic phantom, the most pronounced
      effects occurring in the lung apex.

PMID- 17515395
TI  - Pulmonary artery sarcoma mimicking pulmonary thromboembolism: integrated FDG
      PET/CT.

PMID- 17515396
TI  - Widespread effects of hyperintense lesions on cerebral white matter structure.
AB  - OBJECTIVE: Hyperintense lesions are a common finding on neuroimaging and are
      associated not only with aging, medical illness, and some invasive medical
      procedures, but also with neurologic and psychiatric morbidity. We hypothesized
      that hyperintense lesions are associated with alterations in white matter
      structure beyond the visible lesion boundaries as assessed with diffusion tensor
      imaging (DTI). SUBJECTS AND METHODS: Eighty-two neurologically intact older
      individuals completed brain MRI with DTI. DTI scans were analyzed using regions
      of interest placed in normal-appearing white matter to measure fractional
      anisotropy and diffusivity in the white matter of the frontal lobe, the genu of
      the corpus callosum, and the internal capsule. Hyperintense lesions volumes were
      measured separately in subcortical gray matter and anterior white matter through
      a semiautomated segmentation program. The relationship between lesion volumes and
      DTI measures was examined while controlling for patient age, patient sex, and
      total cerebral volume. RESULTS: Greater anterior white matter lesion volumes were
      associated with higher diffusivity and lower anisotropy in the white matter of
      the dorsolateral prefrontal cortex and with higher diffusivity of the internal
      capsule and white matter lateral to the anterior cingulate cortex. Gray matter
      lesion volumes were associated with higher diffusivity in the genu of the corpus
      callosum and the internal capsule. CONCLUSION: Ischemic hyperintense lesions are
      associated with widespread effects on the structure of the frontal lobe white
      matter and central white matter structures. This may reflect effects of lesions
      on neural circuits or identification of white matter changes that have not yet
      become visible on conventional MRI.

PMID- 17515397
TI  - Parathyroid imaging: technique and role in the preoperative evaluation of primary
      hyperparathyroidism.
AB  - OBJECTIVE: This article discusses the commonly used techniques for imaging the
      parathyroid glands and their role in the preoperative evaluation of patients with
      primary hyperparathyroidism. CONCLUSION: The importance of sonography and
      sestamibi scintigraphy in the preoperative evaluation of patients with primary
      hyperthyroidism has increased with the adoption of minimally invasive
      parathyroidectomy techniques at most medical centers. When the results of these
      studies are concordant, the cure rates of minimally invasive surgery equal those
      of traditional bilateral neck exploration.

PMID- 17515398
TI  - Thymic extension in the superior mediastinum in patients with thymic hyperplasia:
      potential cause of false-positive findings on 18F-FDG PET/CT.
AB  - OBJECTIVE: Although 18F-FDG PET/CT is now well established as an accurate method
      for the staging and restaging of various cancers, it is also well recognized that
      many false-positive results can occur. One such false-positive is activity within
      the superior extent of the thymus in the superior mediastinum. CONCLUSION: We
      reviewed all PET/CT examinations performed in children and young adults under the
      age of 20 years at our institution over a 2-month period. In 11 (12%) of the 93
      examinations, activity was identified in the superior mediastinum of similar
      intensity to the thymus, which is consistent with activity within the superior
      thymic extension. In light of the increasing clinical use of FDG PET/CT for
      cancer imaging, it is important that nuclear medicine physicians and radiologists
      be aware of this phenomenon to avoid misdiagnosis or overstaging of disease.

PMID- 17515399
TI  - Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in
      multiple myeloma.
AB  - The identification of novel tumor-associated antigens, especially those shared
      among patients, is urgently needed to improve the efficacy of immunotherapy for
      multiple myeloma (MM). In this study, we examined whether Dickkopf-1 (DKK1), a
      protein that is not expressed in most normal tissues but is expressed by tumor
      cells from almost all patients with myeloma, could be a good candidate. We
      identified and synthesized DKK1 peptides for human leukocyte antigen (HLA)-A*0201
      and confirmed their immunogenicity by in vivo immunization in HLA-A*0201
      transgenic mice. We detected, using peptidetetramers, low frequencies of DKK1
      peptide-specific CD8-positive (CD8(+)) T cells in patients with myeloma and
      generated peptide-specific T-cell lines and clones from HLA-A*0201-positive (HLA
      A*0201(+)) blood donors and patients with myeloma. These T cells efficiently
      lysed peptide-pulsed but not unpulsed T2 or autologous dendritic cells, DKK1
      positive (DKK1(+))/HLA-A*0201(+) myeloma cell lines U266 and IM-9, and, more
      importantly, HLA-A*0201(+) primary myeloma cells from patients. No killing was
      observed on DKK1(+)/HLA-A*0201-negative (HLA-A*0201(-)) myeloma cell lines and
      primary myeloma cells or HLA-A*0201(+) normal lymphocytes, including B cells.
      These results indicate that these T cells were potent cytotoxic T cells and
      recognized DKK1 peptides naturally presented by myeloma cells in the context of
      HLA-A*0201 molecules. Hence, our study identifies DKK1 as a potentially important
      antigen for immunotherapy in MM.

PMID- 17515400
TI  - One-year acyclovir prophylaxis for preventing varicella-zoster virus disease
      after hematopoietic cell transplantation: no evidence of rebound varicella-zoster
      virus disease after drug discontinuation.
AB  - No consensus exists on whether acyclovir prophylaxis should be given for
      varicella-zoster virus (VZV) prophylaxis after hematopoietic cell transplantation
      because of the concern of "rebound" VZV disease after discontinuation of
      prophylaxis. To determine whether rebound VZV disease is an important clinical
      problem and whether prolonging prophylaxis beyond 1 year is beneficial, we
      examined 3 sequential cohorts receiving acyclovir from day of transplantation
      until engraftment for prevention of herpes simplex virus reactivation (n = 932);
      acyclovir or valacyclovir 1 year (n = 1117); or acyclovir/valacyclovir for at
      least 1 year or longer if patients remained on immunosuppressive drugs (n = 586).
      In multivariable statistical models, prophylaxis given for 1 year significantly
      reduced VZV disease (P < .001) without evidence of rebound VZV disease.
      Continuation of prophylaxis beyond 1 year in allogeneic recipients who remained
      on immunosuppressive drugs led to a further reduction in VZV disease (P = .01)
      but VZV disease developed in 6.1% during the second year while receiving this
      strategy. In conclusion, acyclovir/valacyclovir prophylaxis given for 1 year led
      to a persistent benefit after drug discontinuation and no evidence of a rebound
      effect. To effectively prevent VZV disease in long-term hematopoietic cell
      transplantation survivors, additional approaches such as vaccination will
      probably be required.

PMID- 17515401
TI  - Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV(Delta51)
      NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide
      symporter gene.
AB  - Multiple myeloma is a radiosensitive malignancy that is currently incurable.
      Here, we generated a novel recombinant vesicular stomatitis virus [VSV(Delta51)
      NIS] that has a deletion of methionine 51 in the matrix protein and expresses the
      human sodium iodide symporter (NIS) gene. VSV(Delta51)-NIS showed specific
      oncolytic activity against myeloma cell lines and primary myeloma cells and was
      able to replicate to high titers in myeloma cells in vitro. Iodide uptake assays
      showed accumulation of radioactive iodide in VSV(Delta51)-NIS-infected myeloma
      cells that was specific to the function of the NIS transgene. In bg/nd/xid mice
      with established subcutaneous myeloma tumors, administration of VSV(Delta51)-NIS
      resulted in high intratumoral virus replication and tumor regression. VSV
      associated neurotoxicity was not observed. Intratumoral spread of the infection
      was monitored noninvasively by serial gamma camera imaging of (123)I-iodide
      biodistribution. Dosimetry calculations based on these images pointed to the
      feasibility of combination radiovirotherapy with VSV(Delta51)-NIS plus (131)I.
      Immunocompetent mice with syngeneic 5TGM1 myeloma tumors (either subcutaneous or
      orthotopic) showed significant enhancements of tumor regression and survival when
      VSV(Delta51)-NIS was combined with (131)I. These results show that VSV(Delta51)
      NIS is a safe oncolytic agent with significant therapeutic potential in multiple
      myeloma.

PMID- 17515402
TI  - Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and
      macrothrombocytopenia.
AB  - A pivotal mediator of actin dynamics is the protein cofilin, which promotes
      filament severing and depolymerization, facilitating the breakdown of existing
      filaments, and the enhancement of filament growth from newly created barbed ends.
      It does so in concert with actin interacting protein 1 (Aip1), which serves to
      accelerate cofilin's activity. While progress has been made in understanding its
      biochemical functions, the physiologic processes the cofilin/Aip1 complex
      regulates, particularly in higher organisms, are yet to be determined. We have
      generated an allelic series for WD40 repeat protein 1 (Wdr1), the mammalian
      homolog of Aip1, and report that reductions in Wdr1 function produce a dramatic
      phenotype gradient. While severe loss of function at the Wdr1 locus causes
      embryonic lethality, macrothrombocytopenia and autoinflammatory disease develop
      in mice carrying hypomorphic alleles. Macrothrombocytopenia is the result of
      megakaryocyte maturation defects, which lead to a failure of normal platelet
      shedding. Autoinflammatory disease, which is bone marrow-derived yet nonlymphoid
      in origin, is characterized by a massive infiltration of neutrophils into
      inflammatory lesions. Cytoskeletal responses are impaired in Wdr1 mutant
      neutrophils. These studies establish an essential requirement for Wdr1 in
      megakaryocytes and neutrophils, indicating that cofilin-mediated actin dynamics
      are critically important to the development and function of both cell types.

PMID- 17515403
TI  - Breast cancer molecular subclassification and estrogen receptor expression to
      predict efficacy of adjuvant anthracyclines-based chemotherapy: a biomarker study
      from two randomized trials.
AB  - BACKGROUND: The purpose of this study was to determine the predictive value of
      breast cancer molecular subclassification regarding the benefit of adjuvant
      anthracycline-based chemotherapy. PATIENTS AND METHODS: Tumor samples from 823
      patients included in two randomized trials that compared an anthracycline-based
      chemotherapy with no treatment were used to construct a tissue array. Estrogen
      receptor (ER), Her2, epidermal growth factor receptor, cytokeratine 5/6
      expressions were determined by immunohistochemistry (IHC). The potential
      predictive factors of treatment effect on disease-free survival (DFS) were
      assessed by interaction tests and multivariate analysis. RESULTS: Sixty-four
      (8%), 98 (12%), 109 (14%) and 527 (66%) patients presented a Her2+/ER-, basal
      like, Her2-/ER-/nonbasal and luminal-like breast cancer. ER expression, when
      assessed by IHC, was an independent predictive factor for the benefit of
      chemotherapy on DFS (test for interaction, P = 0.0015). The molecular
      subclassification significantly predicted the efficacy of chemotherapy (test for
      interaction, P = 0.01), but had no significant added value (P = 0.32) as compared
      to the ER by treatment interaction. Adjuvant chemotherapy was associated with an
      adjusted hazard ratio for relapse or death of 0.42 [95% confidence interval (CI):
      0.17-1.05], 0.54 (95% CI: 0.27-1.08), 0.35 (95% CI: 0.18-0.68), 1.07 (95% CI:
      0.81-1.41) for patients with Her2+/ER-, basal-like, Her2-/ER-/nonbasal and
      luminal-like tumors, respectively. CONCLUSION: The breast cancer molecular
      subclassification was predictive for chemotherapy efficacy in adjuvant setting,
      but did not provide significant additional information to ER.

PMID- 17515404
TI  - Clinical relevance of circulating CK-19 mRNA-positive cells detected during the
      adjuvant tamoxifen treatment in patients with early breast cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of adjuvant
      treatment with tamoxifen on the CK-19 mRNA+ cells in patients with early-stage
      breast cancer. PATIENTS AND METHODS: CK-19 mRNA+ cells were prospectively and
      longitudinally detected using a specific real-time PCR assay for CK-19 mRNA in
      119 patients with estrogen and/or progesterone receptor-positive tumors during
      the period of tamoxifen administration. RESULTS: Twenty-two (18.5%) patients had
      detectable CK-19 mRNA+ cells after the completion of adjuvant chemotherapy and in
      15 (68.2%) of them adjuvant tamoxifen could not eliminate these cells
      (persistently positive). In 68 (57.1%) patients, no CK-19 mRNA+ cells could be
      detected throughout the follow-up period (persistently negative). Seven (46.7%)
      of the 15 persistently positive and six (8.8%) of the 68 persistently negative
      patients developed disease recurrence (P = 0.00026). Persistency of CK-19 mRNA+
      cells was associated with a significantly lower median disease-free interval (P =
      0.0001) and overall survival (P = 0.0005). Multivariate analysis revealed that
      the detection of CK-19 mRNA+ cells during the administration of tamoxifen was
      associated with an increased risk of relapse [hazard ratio (HR) = 22.318, P =
      0.00006] and death (HR = 13.954, P < 0.00001). CONCLUSIONS: The detection of CK
      19 mRNA+ cells throughout the period of adjuvant tamoxifen treatment is an
      independent poor prognostic factor in patients with early breast cancer.

PMID- 17515405
TI  - Night terrors: women's experiences of (not) sleeping where there is domestic
      violence.
AB  - The management of sleep is embedded within the social context of individuals'
      lives. This article is based on an exploratory study using focus groups of the
      sleep problems encountered by 17 women survivors of domestic violence. It argues
      that fear becomes the organizing framework for the management of sleep and
      illustrates how this takes place both while living with the perpetrators of
      violence and after the women have been rehoused. It argues that sleep deprivation
      is a method used by the perpetrators to exert control over women and that this
      has long-term implications for women's physical and mental health.

PMID- 17515406
TI  - Experiences with intimate partner violence among Latina women.
AB  - This study examined experiences with intimate partner violence in 292 Latina
      women classified as U.S. born, immigrant, or migrant-seasonal workers. High
      lifetime rates of violence were found, with 33.9% reporting physical violence,
      20.9% reporting sexual coercion, and 82.5% reporting psychological aggression.
      Rates of violence in the preceding year were also high, with 18.5% experiencing
      physical violence, 14.4% experiencing sexual coercion, and 72.6% experiencing
      psychological aggression. Participants' marital status and partners' substance
      use were associated with victimization. The present findings suggest the need for
      screening for intimate partner violence and associated risk factors in settings
      that serve Latina women.

PMID- 17515407
TI  - In their own voices: a qualitative study of women's risk for intimate partner
      violence and HIV in South Africa.
AB  - This study qualitatively examines the intersections of risk for intimate partner
      violence (IPV) and HIV infection in South Africa. Eighteen women seeking services
      for relationship violence were asked semistructured questions regarding their
      abusive experiences and HIV risk. Participants had experienced myriad forms of
      abuse, which reinforced each other to create a climate that sustained abuse and
      multiplied HIV risk. Male partners having multiple concurrent sexual
      relationships, and poor relationship communication compounded female
      vulnerability to HIV and abuse. A social environment of silence, male power, and
      economic constraints enabled abuse to continue. "Breaking the silence" and
      women's empowerment were suggested solutions.

PMID- 17515408
TI  - A specialized domestic violence court in South Carolina: an example of procedural
      justice for victims and defendants.
AB  - The current research details interviews with 50 victims and 50 defendants who
      participated in a specialized criminal domestic violence court in Lexington
      County, South Carolina. These victims and defendants indicated satisfaction with
      their court experiences, thought the process allowed them to voice their views,
      felt they were treated with respect, and were generally satisfied with the
      outcome of their cases. Court observations and interviews with court personnel
      confirmed that this court has successfully incorporated victims and defendants
      into the decision-making process while also providing a fair system to address
      the issue of violence against women.

PMID- 17515409
TI  - The impact of bullying and sexual harassment on middle and high school girls.
AB  - The impact of bullying and sexual harassment on six health outcomes among middle
      school girls were compared to these outcomes among high school girls. High school
      girls experienced more bullying and sexual harassment and poorer health outcomes
      than their middle school counterparts, but the impact of these experiences was
      less among high school students. Differences in outcomes may be the result of
      better support systems and coping mechanisms among high school girls and/or
      challenging developmental changes during middle school. Sexual orientation, race,
      and disability had some notable relationships to bullying and sexual harassment
      experiences as well as health outcomes.

PMID- 17515410
TI  - Lessons of the kiss.

PMID- 17515411
TI  - Molecular and cellular studies in evolutionary physiology of natural vertebrate
      populations: influences of individual variation and genetic components on
      sampling and measurements.
AB  - Studies combining ecological, genetic and physiological approaches are needed in
      evolutionary biology. Although the combination of approaches has been emphasized,
      such studies have been rare with regard to molecular and cellular studies on
      natural vertebrate populations. The major reasons for this are that the
      generation time of vertebrates is long and it is difficult to find a molecular or
      cell physiological measurement that is both relevant for the fitness of the
      population and can be repeated an adequate number of times to enable estimations
      of individual variability. The paucity of suitable physiological parameters is
      partly due to the fact that most physiological studies have not been directed
      towards understanding the behaviour of populations but towards understanding the
      basic mechanisms of the function of individuals. Also, physiological measurements
      that appear most relevant from the point of view of evolutionary studies are
      often integrative functions, composed of the function of many genes. When
      dissecting the integrative functions into components, it is often observed that
      the same integrative response can be achieved via different routes, i.e. changes
      in the responses of different genes. To enable cellular and molecular
      physiological studies to be increasingly combined with ecological and genetic
      studies, it is important that such studies include and report individual
      variability and that the sample size is increased. In addition, more
      sophisticated statistical methods should be used than is traditionally done, and
      when the function of most genes in the integrative response are not known,
      techniques such as QTL mapping should be used. Hitherto in vertebrates, the
      methodology has mainly been used in production biology (e.g. meat or milk
      production). With regard to combining genomic and physiological studies, one must
      bear in mind that the massive datasets associated with genomic studies need to be
      further enlarged to enable estimates of individual variation. It is also
      important to remember that microarray and proteomic data give the levels of mRNA
      and proteins, respectively. Since the function of the protein can be regulated
      independently of its transcription or its level in the cell, direct physiological
      measurements are also needed if estimations of protein activity in the
      individuals of a population are wanted.

PMID- 17515412
TI  - Use of portable ultrasonography as a nondestructive method for estimating
      reproductive effort in lizards.
AB  - Obtaining population-level life history data such as egg and clutch size in
      reptiles has most often required that individuals be sacrificed. This prevents a
      reexamination of individuals over intra-annual and inter-annual time scales,
      limiting insight into the effects of varying environmental conditions on
      reproductive output. Here, we test the use of a laptop-sized portable ultrasound
      imaging system as a nondestructive means for quantifying reproductive investment
      in five species of lizards with a range of body sizes, forms and life histories.
      Ultrasound scans produced egg counts that were accurate for clutch sizes of two
      to seven eggs, and provided good estimates (within 5.5+/-1.69 eggs, mean +/-
      s.e.m., relative error 21%) for clutch sizes of between 18 and 41 eggs. Egg
      measurements using virtual calipers produced average egg volumes that deviated
      from actual volumes by 0.09+/-0.01 cm(3) (relative error 25.9%), and estimated
      clutch volumes that differed from actual volumes by 1.03+/-0.26 cm(3) (relative
      error 29.5%). We also monitored development in five lizard species and found that
      changes in follicle and egg size and degree of embryonic development can be
      measured over periods of just a few days.

PMID- 17515413
TI  - Morphological diversity of medusan lineages constrained by animal-fluid
      interactions.
AB  - Cnidarian medusae, commonly known as jellyfish, represent the earliest known
      animal taxa to achieve locomotion using muscle power. Propulsion by medusae
      requires the force of bell contraction to generate forward thrust. However,
      thrust production is limited in medusae by the primitive structure of their
      epitheliomuscular cells. This paper demonstrates that constraints in available
      locomotor muscular force result in a trade-off between high-thrust swimming via
      jet propulsion and high-efficiency swimming via a combined jet-paddling
      propulsion. This trade-off is reflected in the morphological diversity of
      medusae, which exhibit a range of fineness ratios (i.e. the ratio between bell
      height and diameter) and small body size in the high-thrust regime, and low
      fineness ratios and large body size in the high-efficiency regime. A quantitative
      model of the animal-fluid interactions that dictate this trade-off is developed
      and validated by comparison with morphological data collected from 660 extant
      medusan species ranging in size from 300 microm to over 2 m. These results
      demonstrate a biomechanical basis linking fluid dynamics and the evolution of
      medusan bell morphology. We believe these to be the organising principles for
      muscle-driven motility in Cnidaria.

PMID- 17515414
TI  - Interspecific comparison of hydrodynamic performance and structural properties
      among intertidal macroalgae.
AB  - Macroalgae use flexibility and reconfiguration, i.e. the alteration of shape,
      size and orientation as water velocity increases, to reduce the hydrodynamic
      forces imposed in the wave-swept rocky intertidal zone. Quantifying the effects
      of flexibility on hydrodynamic performance is difficult, however, because the
      mechanisms of reconfiguration vary with water velocity and the relationship
      between algal solid mechanics and hydrodynamic performance is poorly understood.
      In this study, the hydrodynamic performance, morphology and solid mechanics of 10
      rocky shore macroalgal species were quantified to evaluate the influences of
      flexibility and morphology on reconfiguration. Hydrodynamic performance was
      measured in a flume by direct measurement of changes in size and shape during
      reconfiguration across a wide range of velocities, material stiffness was
      quantified with standard materials testing, and structural properties were
      calculated from material and morphological data. Hydrodynamic parameters varied
      significantly among species, indicating variation in the magnitude of
      reconfiguration and the velocities required for full reconfiguration. Structural
      properties also varied among species, and were correlated with hydrodynamic
      performance in some instances. The relationship between hydrodynamic and
      structural properties is velocity dependent, such that flexibility influences
      different aspects of reconfiguration at low and high velocities. Groups are
      identifiable among species based on hydrodynamic and structural properties,
      suggesting that these properties are useful for addressing functional-form
      hypotheses and the effects of hydrodynamic disturbance on macroalgal communities.

PMID- 17515415
TI  - Validation of vertical ground reaction forces on individual limbs calculated from
      kinematics of horse locomotion.
AB  - The purpose of this study was to determine whether individual limb forces could
      be calculated accurately from kinematics of trotting and walking horses. We
      collected kinematic data and measured vertical ground reaction forces on the
      individual limbs of seven Warmblood dressage horses, trotting at 3.4 m s(-1) and
      walking at 1.6 m s(-1) on a treadmill. First, using a segmental model, we
      calculated from kinematics the total ground reaction force vector and its moment
      arm relative to each of the hoofs. Second, for phases in which the body was
      supported by only two limbs, we calculated the individual reaction forces on
      these limbs. Third, we assumed that the distal limbs operated as linear springs,
      and determined their force-length relationships using calculated individual limb
      forces at trot. Finally, we calculated individual limb force-time histories from
      distal limb lengths. A good correspondence was obtained between calculated and
      measured individual limb forces. At trot, the average peak vertical reaction
      force on the forelimb was calculated to be 11.5+/-0.9 N kg(-1) and measured to be
      11.7+/-0.9 N kg(-1), and for the hindlimb these values were 9.8+/-0.7 N kg(-1)
      and 10.0+/-0.6 N kg(-1), respectively. At walk, the average peak vertical
      reaction force on the forelimb was calculated to be 6.9+/-0.5 N kg(-1) and
      measured to be 7.1+/-0.3 N kg(-1), and for the hindlimb these values were 4.8+/
      0.5 N kg(-1) and 4.7+/-0.3 N kg(-1), respectively. It was concluded that the
      proposed method of calculating individual limb reaction forces is sufficiently
      accurate to detect changes in loading reported in the literature for mild to
      moderate lameness at trot.

PMID- 17515416
TI  - Low speed maneuvering flight of the rose-breasted cockatoo (Eolophus
      roseicapillus). I. Kinematic and neuromuscular control of turning.
AB  - Maneuvering flight has long been recognized as an important component of the
      natural behavior of many bird species, but has been the subject of little
      experimental work. Here we examine the kinematics and neuromuscular control of
      turning flight in the rose-breasted cockatoo Eolophus roseicapillus (N=6),
      testing predictions of maneuvering flight and control based on aerodynamic theory
      and prior kinematic and neuromuscular studies. Six cockatoos were trained to
      navigate between two perches placed in an L-shaped flight corridor, making a 90
      degrees turn midway through each flight. Flights were recorded with three
      synchronized high-speed video cameras placed outside the corridor, allowing a
      three-dimensional reconstruction of wing and body kinematics through the turn. We
      simultaneously collected electromyography recordings from bilateral implants in
      the pectoralis, supracoracoideus, biceps brachii and extensor metacarpi radialis
      muscles. The cockatoos maneuvered using flapping, banked turns with an average
      turn radius of 0.92 m. The mean rate of change in heading during a complete
      wingbeat varied through the turn and was significantly correlated to roll angle
      at mid-downstroke. Changes in roll angle were found to include both within
      wingbeat and among-wingbeat components that bear no direct relationship to one
      another. Within-wingbeat changes in roll were dominated by the inertial effects
      while among-wingbeat changes in roll were likely the result of both inertial and
      aerodynamic effects.

PMID- 17515417
TI  - Low speed maneuvering flight of the rose-breasted cockatoo (Eolophus
      roseicapillus). II. Inertial and aerodynamic reorientation.
AB  - The reconfigurable, flapping wings of birds allow for both inertial and
      aerodynamic modes of reorientation. We found evidence that both these modes play
      important roles in the low speed turning flight of the rose-breasted cockatoo
      Eolophus roseicapillus. Using three-dimensional kinematics recorded from six
      cockatoos making a 90 degrees turn in a flight corridor, we developed predictions
      of inertial and aerodynamic reorientation from estimates of wing moments of
      inertia and flapping arcs, and a blade-element aerodynamic model. The blade
      element model successfully predicted weight support (predicted was 88+/-17% of
      observed, N=6) and centripetal force (predicted was 79+/-29% of observed, N=6)
      for the maneuvering cockatoos and provided a reasonable estimate of mechanical
      power. The estimated torque from the model was a significant predictor of roll
      acceleration (r(2)=0.55, P<0.00001), but greatly overestimated roll magnitude
      when applied with no roll damping. Non-dimensional roll damping coefficients of
      approximately -1.5, 2-6 times greater than those typical of airplane flight
      dynamics (approximately -0.45), were required to bring our estimates of
      reorientation due to aerodynamic torque back into conjunction with the measured
      changes in orientation. Our estimates of inertial reorientation were
      statistically significant predictors of the measured reorientation within
      wingbeats (r(2) from 0.2 to 0.37, P<0.0005). Components of both our inertial
      reorientation and aerodynamic torque estimates correlated, significantly, with
      asymmetries in the activation profile of four flight muscles: the pectoralis,
      supracoracoideus, biceps brachii and extensor metacarpi radialis (r(2) from 0.27
      to 0.45, P<0.005). Thus, avian flight maneuvers rely on production of asymmetries
      throughout the flight apparatus rather than in a specific set of control or
      turning muscles.

PMID- 17515418
TI  - Sharks need the lateral line to locate odor sources: rheotaxis and eddy
      chemotaxis.
AB  - Odor plumes are complex, dynamic, three-dimensional structures used by many
      animals to locate food, mates, home sites, etc. Yet odor itself has no
      directional properties. Animals use a variety of different senses to obtain
      directional information. Since most odor plumes are composed of dispersing odor
      patches and dissipating vorticity eddies, aquatic animals may localize odor
      sources by simultaneous analysis of chemical and hydrodynamic dispersal fields, a
      process referred to as eddy chemotaxis. This study examines the contributions of
      olfaction, mechanoreception and vision to odor source localization in a shark,
      the smooth dogfish Mustelus canis. Two parallel, turbulent plumes were created in
      an 8 m flume: squid rinse odor and seawater control. Minimally turbulent ;oozing'
      sources of odor and seawater control were physically separated from sources of
      major turbulence by placing a brick downstream from each oozing source, creating
      two turbulent wakes, one or the other flavored with food odor. This created four
      separate targets for the sharks to locate. Animals were tested under two light
      conditions (fluorescent and infrared) and in two sensory conditions (lateral line
      intact and lateral line lesioned by streptomycin). Intact animals demonstrated a
      preference for the odor plume over the seawater plume and for the source of
      odor/turbulence (the brick on the odor side) over the source of the odor alone
      (the odor-oozing nozzle). Plume and target preference and search time were not
      significantly affected by light condition. In the light, lesioning the lateral
      line increased search time but did not affect success rate or plume preference.
      However, lesioned animals no longer discriminated between sources of turbulent
      and oozing odor. In the dark, search time of lesioned animals further increased,
      and the few animals that located any of the targets did not discriminate between
      odor and seawater plumes, let alone targets. These results demonstrate for the
      first time that sharks require both olfactory and lateral line input for
      efficient and precise tracking of odor-flavored wakes and that visual input can
      improve food-finding performance when lateral line information is not available.
      We distinguish between rheotaxis: orientation to the large-scale flow field
      (olfaction, vision and superficial lateral line), eddy chemotaxis: tracking the
      trail of small-scale, odor-flavored turbulence (olfaction and lateral line
      canals), and pinpointing the source of the plume (lateral line canals and
      olfaction).

PMID- 17515419
TI  - Responses to hypoxia and recovery: repayment of oxygen debt is not associated
      with compensatory protein synthesis in the Amazonian cichlid, Astronotus
      ocellatus.
AB  - Oxygen consumption, as an indicator of routine metabolic rate (RoMR), and tissue
      specific changes in protein synthesis, as measured by (3)H-labelled phenylalanine
      incorporation rates, were determined in Astronotus ocellatus to investigate the
      cellular mechanisms behind hypoxia-induced metabolic depression and recovery.
      RoMR was significantly depressed, by approximately 50%, when dissolved oxygen
      levels reached 10% saturation (0.67+/-0.01 mg l(-1) at 28+/-1 degrees C). This
      depression in RoMR was accompanied by a 50-60% decrease in liver, heart and gill
      protein synthesis, but only a 30% decrease in brain protein synthesis. During
      recovery from hypoxia, an overshoot in RoMR to 270% of the normoxic rate was
      observed, indicating the accumulation of an oxygen debt during hypoxia. This
      conclusion was consistent with significant increase in plasma lactate levels
      during the hypoxic exposure, and the fact that lactate levels rapidly returned to
      pre-hypoxic levels. In contrast, a hyperactivation of protein synthesis did not
      occur, suggesting the overshoot in oxygen consumption during recovery is
      attributed to an increase in cellular processes other than protein synthesis.

PMID- 17515420
TI  - Mechanisms of acid-base regulation in the African lungfish Protopterus annectens.
AB  - African lungfish Protopterus annectens utilized both respiratory and metabolic
      compensation to restore arterial pH to control levels following the imposition of
      a metabolic acidosis or alkalosis. Acid infusion (3 mmol kg(-1) NH(4)Cl) to lower
      arterial pH by 0.24 units increased both pulmonary (by 1.8-fold) and branchial
      (by 1.7-fold) ventilation frequencies significantly, contributing to 4.8-fold and
      1.9-fold increases in, respectively, aerial and aquatic CO(2) excretion. This
      respiratory compensation appeared to be the main mechanism behind the restoration
      of arterial pH, because even though net acid excretion (J(net)H(+)) increased
      following acid infusion in 7 of 11 fish, the mean increase in net acid excretion,
      184.5+/-118.5 micromol H(+) kg(-1) h(-1) (mean +/- s.e.m., N=11), was not
      significantly different from zero. Base infusion (3 mmol kg(-1) NaHCO(3)) to
      increase arterial pH by 0.29 units halved branchial ventilation frequency,
      although pulmonary ventilation frequency was unaffected. Correspondingly, aquatic
      CO(2) excretion also fell significantly (by 3.7-fold) while aerial CO(2)
      excretion was unaffected. Metabolic compensation consisting of negative net acid
      excretion (net base excretion) accompanied this respiratory compensation, with
      J(net)H(+) decreasing from 88.5+/-75.6 to -337.9+/-199.4 micromol H(+) kg(-1) h(
      1) (N=8). Partitioning of net acid excretion into renal and extra-renal (assumed
      to be branchial and/or cutaneous) components revealed that under control
      conditions, net acid excretion occurred primarily by extra-renal routes. Finally,
      several genes that are involved in the exchange of acid-base equivalents between
      the animal and its environment (carbonic anhydrase, V-type H(+)-ATPase and
      Na(+)/HCO (-)(3) cotransporter) were cloned, and their branchial and renal mRNA
      expressions were examined prior to and following acid or base infusion. In no
      case was mRNA expression significantly altered by metabolic acid-base
      disturbance. These findings suggest that lungfish, like tetrapods, alter
      ventilation to compensate for metabolic acid-base disturbances, a mechanism that
      is not employed by water-breathing fish. Like fish and amphibians, however, extra
      renal routes play a key role in metabolic compensation.

PMID- 17515421
TI  - Diving and foraging energetics of the smallest marine mammal, the sea otter
      (Enhydra lutris).
AB  - As the smallest and one of the most recently evolved marine mammals, sea otters
      face physiological challenges rarely encountered by larger, more derived aquatic
      species. To examine the effect of these challenges on foraging costs and
      resultant daily energy budgets, we measured the energetics of resting, grooming,
      diving and foraging for adult, male sea otters. The energy expended for these
      different behaviors as determined from open flow respirometry was then
      standardized across activity budgets measured for wild sea otters to estimate
      field metabolic rates (FMR). We found that the metabolic rate of captive otters
      performing single dives ranging in duration from 40 to 192 s was 17.6+/-0.5 ml
      O(2) kg(-1) min(-1) and only 1.3 times resting rates. This rate increased
      significantly if the animals foraged during submergence. The cost of a foraging
      dive for sea otters was nearly twice that predicted for phocid seals, which was
      attributed in part to elevated locomotor costs associated with buoyancy and
      swimming style. Our behavioral studies indicate that wild sea otters spend the
      greatest proportion of the day feeding and resting, with the largest daily energy
      expenditure (6.1+/-1.1 MJ day(-1)) associated with foraging. The resulting mean
      FMR for wild sea otters based on the energy expended for all behaviors was 15.7+/
      2.7 MJ day(-1) and matched predicted FMR values based upon a regression of known
      FMR values for other marine mammals across a range of body sizes. This was
      achieved by counterbalancing elevated foraging costs with prolonged periods of
      rest on the water surface.

PMID- 17515422
TI  - Intermediary metabolism of Arctic char Salvelinus alpinus during short-term
      salinity exposure.
AB  - The migration of Arctic char Salvelinus alpinus from freshwater to seawater
      requires a substantial reorganization of the osmoregulatory tissues to regulate
      plasma ion levels. These modifications have an inherent metabolic cost, which
      must be met through the upregulation of intermediary metabolism. Arctic char
      intermediary metabolism was monitored during the initial 96 h of seawater
      acclimation through measurement of key enzymes in gill, liver, red and white
      muscle as well as tissue and blood free amino acid (FAA) levels, and plasma
      glucose and non-esterified fatty acid content. In general, seawater exposure
      stimulated large changes in amino acid metabolism, but no change in lipid or
      carbohydrate metabolism. White muscle FAA content increased significantly
      following seawater exposure, with levels of essential FAAs doubling after 96 h.
      Similar increases were seen in the plasma, suggesting a rapid mobilization of
      FAAs to the circulation. These changes were accompanied by significant increases
      in the activities of enzymes involved in amino acid metabolism in the gill,
      liver, red and white muscle, suggesting seawater-acclimated fish have an enhanced
      capacity for energy production from amino acids. Increased energy requirements
      were evident in the gill of seawater-acclimated char, as citrate synthase
      activity increased significantly. The results of this study suggest a rapid
      upregulation of amino acid metabolism may be critical for the successful
      acclimation of Arctic char to seawater.

PMID- 17515423
TI  - Allatotropin-like peptide released by Malpighian tubules induces hindgut activity
      associated with diuresis in the Chagas disease vector Triatoma infestans (Klug).
AB  - Haematophagous insects incorporate a large amount of blood with each meal,
      producing a big quantity of urine in a few hours to eliminate the excess water
      and Na(+). Malpighian tubules (MTs) have traditionally been seen as a system that
      responds to neuroendocrine stimulus. In a related paper, we demonstrated that MTs
      of Triatoma infestans produce an autonomous endocrine secretion of an
      allatotropin-like (AT-like) peptide. In the present study, we report a
      myostimulatory activity of AT at the level of the hindgut (HG), associated with
      endocrine mechanisms regulating post-prandial diuresis. Allatotropin induced an
      increase in frequency and intensity of peristaltic contractions at the level of
      the HG. The release of the HG content in MTs-HG in vitro preparations undergoing
      an osmotic shock occurred at different times, depending on the number of MTs
      present, and there was no release in treatments without MTs. The application of
      an AT-antiserum to MTs-HG preparations undergoing osmotic shock produced a delay
      or a long-term blockade of diuresis, depending on the antiserum dilution applied.
      Similar results were obtained when AT-antiserum was applied in vivo prior to
      blood intake, decreasing the volume of urine eliminated during the first 2 h. Our
      results allow us to assign a specific endocrine function to the AT-like peptide
      released by MTs that is linked to the elimination of urine after blood meals.

PMID- 17515424
TI  - Phosphatidylcholine profile-mediated group recognition in catfish.
AB  - Animal groups are integrated by emission of discrete signals from members, so
      called social signals, which have evolved for each species. Among communication
      signals, chemical signals play an important role for recognition of group
      membership. The catfish Plotosus lineatus forms a dense school immediately after
      hatching, and school recognition is under the control of chemical signals emitted
      by the school members. The key substance(s) governing this recognition are
      deduced to be a mixture of phosphatidylcholines (PC). To substantiate this
      hypothesis that a mixture of PC molecular species functions as recognition of
      school-specific odor, we examined the ability of P. lineatus to discriminate
      between familiar and unfamiliar PCs. P. lineatus responded only to PCs from a
      familiar school, and not to those from unfamiliar schools. PC molecular species
      were then analyzed by quantitative high performance liquid chromatography, which
      resulted in not only a complex mixture of PC molecular species, but also school
      specific PC profiles. Furthermore, multivariate analysis of the quantified PC
      peaks revealed the presence of various PC profiles. Finally, we showed that the
      modification of PC profiles disrupts the recognition of school odor in P.
      lineatus. Therefore, we conclude that the recognition of school odor in P.
      lineatus is governed by school-specific PC profiles.

PMID- 17515425
TI  - Whole-animal metabolic rate is a repeatable trait: a meta-analysis.
AB  - Repeatability studies are gaining considerable interest among physiological
      ecologists, particularly in traits affected by high environmental/residual
      variance, such as whole-animal metabolic rate (MR). The original definition of
      repeatability, known as the intraclass correlation coefficient, is computed from
      the components of variance obtained in a one-way ANOVA on several individuals
      from which two or more measurements are performed. An alternative estimation of
      repeatability, popular among physiological ecologists, is the Pearson product
      moment correlation between two consecutive measurements. However, despite the
      more than 30 studies reporting repeatability of MR, so far there is not a
      definite synthesis indicating: (1) whether repeatability changes in different
      types of animals; (2) whether some kinds of metabolism are more repeatable than
      others; and most important, (3) whether metabolic rate is significantly
      repeatable. We performed a meta-analysis to address these questions, as well as
      to explore the historical trend in repeatability studies. Our results show that
      metabolic rate is significantly repeatable and its effect size is not
      statistically affected by any of the mentioned factors (i.e. repeatability of MR
      does not change in different species, type of metabolism, time between
      measurements, and number of individuals). The cumulative meta-analysis revealed
      that repeatability studies in MR have already reached an asymptotical effect size
      with no further change either in its magnitude and/or variance (i.e. additional
      studies will not contribute significantly to the estimator). There was no
      evidence of strong publication bias.

PMID- 17515426
TI  - Metabolic rate of nocturnal incubation in female great tits, Parus major, in
      relation to clutch size measured in a natural environment.
AB  - To study the energetic costs of incubation in relation to clutch size, clutch
      sizes were manipulated and the metabolic rate of female great tits, Parus major
      (Linnaeus), during nocturnal incubation (MR(inc)) was measured using mobile
      oxygen analysers. Individuals were measured on consecutive nights while
      incubating their own or manipulated clutches. The experiment was performed under
      field conditions in order to place possible effects of clutch size manipulation
      within the context of other factors explaining variation in MR(inc). Females
      spent more energy when incubating enlarged clutches as compared with controls (6
      10% more energy for three additional eggs) but did not spend significantly less
      energy when incubating reduced clutches. MR(inc) was strongly negatively related
      to ambient temperature. The effect of clutch enlargement is consistent with
      previous studies whereas the absence of an effect of clutch reduction is not. The
      small effect of clutch enlargement on MR(inc) highlights the need for further
      studies to include measurements of daily energy expenditure in order to judge how
      important energy expenditure can be in explaining fitness consequences of
      incubating experimentally enlarged clutches.

PMID- 17515427
TI  - Behavioural and physiological responses to increased foraging effort in male
      mice.
AB  - Free-living animals must forage for food and hence may face energetic constraints
      imposed by their natural environmental conditions (e.g. ambient temperature, food
      availability). Simulating the variation in such constraints, we have
      experimentally manipulated the rate of work (wheel running) mice must do to
      obtain their food, and studied the ensuing behavioural and physiological
      responses. This was done with a line of mice selectively bred for high
      spontaneous wheel running and a randomly bred control line that vary in the
      amount of baseline wheel-running activity. We first determined the maximum
      workload for each individual. The maximum workload animals could engage in was
      around 23 km d(-1) in both control and activity-selected mice, and was not
      associated with baseline wheel-running activity. We then kept mice at 90% of
      their individual maximum and measured several physiological and behavioural
      traits. At this high workload, mice increased wheel-running activity from an
      average of 10 to 20 km d(-1), and decreased food intake and body mass by
      approximately 20%. Mass-specific resting metabolic rate strongly decreased from
      1.43 to 0.98 kJ g(-1) d(-1), whereas daily energy expenditure slightly increased
      from 2.09 to 2.25 kJ g(-1) d(-1). Costs of running decreased from 2.3 to 1.6 kJ
      km(-1) between baseline and workload conditions. At high workloads, animals were
      in a negative energy balance, resulting in a sharp reduction in fat mass as well
      as a slight decrease in dry lean mass. In addition, corticosterone levels
      increased, and body temperature was extremely low in some animals at high
      workloads. When challenged to work for food, mice thus show significant
      physiological and behavioural adjustments.

PMID- 17515428
TI  - Screening for intimate partner violence: the impact of screener and screening
      environment on victim comfort.
AB  - The barriers that professionals face when screening victims for intimate partner
      violence (IPV) are well studied. The specific barriers that victims face however
      when being screened are not. The authors sought to identify characteristics of
      the screener and screening environment that make a victim feel more or less
      comfortable when disclosing a history of IPV. One hundred forty self-reported
      female victims of IPV completed a survey regarding their experiences with
      screening and degree of comfort with certain traits of the screener and the
      screening environment. Women demonstrated a preference to be screened by a woman,
      someone of the same race, a provider aged 30 to 50 years, and without anyone else
      present. Screeners should be aware of characteristics that impact victim comfort
      and should provide multiple opportunities for women to disclose IPV in a safe,
      respectful, and culturally effective environment.

PMID- 17515429
TI  - The myth of offenders' deception on self-report measure predicting recidivism:
      example from the Self-Appraisal Questionnaire (SAQ).
AB  - Two studies were conducted to investigate the vulnerability of the Self-Appraisal
      Questionnaire (SAQ) to deception and self-presentation biases. The SAQ is a self
      report measure used to predict recidivism and guide institutional and program
      assignments. In the first study, comparisons were made between 429 volunteer
      offenders who completed the SAQ for research purposes and 75 offenders who
      completed the SAQ as a part of the psychological assessments process required for
      consideration for early release. In the second study, 106 participants over two
      sessions completed the SAQ and the Balanced Inventory of Desirable Responding.
      Participants completed both measures under two separate sets of instructions: (a)
      Answers would be used for research purposes, and (b) answers would be used for
      making decisions about their release to the community. Results from both studies
      reaffirmed previous findings that the SAQ is not vulnerable to deception, lying,
      and self-presentation biases.

PMID- 17515430
TI  - The effect of childhood trauma on later psychological adjustment.
AB  - This study examined whether adult attachment and cognitive distortion mediate the
      relationship between childhood trauma and psychological adjustment. The
      participants were 219 students (40 men and 117 women) enrolled in a university
      degree. Participants completed the Childhood Trauma Questionnaire, which assessed
      retrospective accounts of childhood trauma; the Relationships Scales
      Questionnaire, which measured two dimensions of adult attachment (model-of-self
      and model-of-other); the Cognitive Distortions Scale, which measured internal
      attributions and perceptions of controllability; and the Trauma Symptom
      Inventory, which assessed posttraumatic symptoms and was used in this study to
      measure psychological adjustment. Results supported the hypothesis that model-of
      self and cognitive distortion are related constructs. The influence of model-of
      self on psychological adjustment however was only via its effect on cognitive
      processes. In other words, a negative model-of-self influenced cognitive
      distortion, which in turn influenced the expression of symptoms in adults
      reporting a history of childhood trauma. The implications for therapy were
      considered.

PMID- 17515431
TI  - Intimate partner violence within a cohort of Pacific mothers living in New
      Zealand.
AB  - Maternal reports of intimate partner violence (IPV) were obtained from a cohort
      of Pacific mothers living in New Zealand. The Conflict Tactics Scale was
      completed by 1,095 women who had given birth in the past 12 months, and who were
      married or living with a partner as married. The 12-month prevalence of
      "victimization" through verbal aggression was 77%, 21% for "minor" physical
      violence, and 11% for "severe" physical violence. The 12-month prevalence of
      "perpetration" of verbal aggression against a partner was 90%, 35% for "minor"
      physical violence, and 19% for "severe" violence towards their partner. The
      experience of social inequality and acculturation are associated with IPV, albeit
      differentially across the experience of victimization and perpetration. Factors
      significantly associated with victimization are ethnicity, maternal education,
      social marital status and household income. Factors significantly associated with
      perpetration are ethnicity, cultural alignment, maternal birthplace and alcohol
      consumption since the birth of the child.

PMID- 17515432
TI  - To blame or not to blame: influences of target race and observer sex on rape
      blame attribution.
AB  - There is a paucity of research on the influence of racist and sexist stereotypes
      in rape blame attribution, including the jezebel and matriarch stereotypes of
      Black women. This study extends the literature by examining how victim race,
      perpetrator race, and participant sex affect perceptions of a rape survivor's
      promiscuity (jezebel stereotype) and strength and/or toughness (matriarch
      stereotype). The myth of the Black male sexual predator of White women is also
      investigated. Data provided partial support for the jezebel stereotype. There
      were also contradictory findings supporting and challenging the acceptance of the
      Black rapist of White women stereotype. No significant differences were found for
      the matriarch stereotype. Reasons for and implications of findings are explored.

PMID- 17515433
TI  - Perceived neighborhood social disorder and attitudes toward reporting domestic
      violence against women.
AB  - This study aims to explore the relationship between perceived neighborhood social
      disorder and attitudes toward reporting domestic violence against women. Data
      from a national representative sample (N = 14,994) of Spaniards 18 years old and
      older were used. Multivariate logistic regression analysis showed that perceived
      neighborhood social disorder is negatively associated with attitudes toward
      reporting domestic violence against women. These results take into account the
      potential confounding effects of gender, age, socioeconomic status, perceived
      frequency of domestic violence against women, and size of city on reporting
      attitudes. Findings support the idea that to reduce and prevent domestic violence
      against women, it is also important to address those conditions leading to
      mistrust between people and diminished social control such as concentrated
      disadvantage and disorder.

PMID- 17515434
TI  - An exploratory study of women arrested for intimate partner violence: violent
      women or violent resistance?
AB  - With the advent of mandatory and pro-arrest laws for incidents of intimate
      partner violence, there has been an increase in the number of women arrested for
      domestic violence. Several explanations are posed in the literature that attempt
      to explain such a rise, including the hypothesis that women are being arrested
      not for offensive violence but rather for defensive violence. Few studies,
      however, have used empirical data to support such arguments. This exploratory
      study examines the characteristics of women arrested for intimate personal
      violence. Particular attention is paid to women arrested with their partner
      (i.e., dual arrestees) and the contextual characteristics of dual arrestee
      incidents. Important differences are uncovered in the context and consequences of
      arrest for dual arrestees (n = 21) compared to women arrested alone as the
      offender (n = 49). Implications of these findings and further research directions
      are discussed.

PMID- 17515435
TI  - System intervention problems in child sexual abuse investigations: the mothers'
      perspectives.
AB  - On learning that her child was sexually abused, a mother must interact with
      professionals charged with the implementation of investigations, treatment, and
      legal remedies. This qualitative study, based on data from three focus groups (n
      = 19) and open-ended survey questions (n = 40), documents mothers' experiences
      with these professionals. Mothers report a lack of support from many
      professionals including receiving poor services, being criticized, insensitivity
      to their concerns, and being accused of false allegations and state that they
      have difficulty seeing the "system" as a positive future resource. Mothers
      reported appreciation for helpful professionals, whom they most often identified
      as therapists. Determining which mothers are reporting system problems and the
      effect of negative maternal-system interactions on mother and child outcomes are
      recommended as follow-up research.

PMID- 17515436
TI  - The spectrum of cardiac anomalies in Noonan syndrome as a result of mutations in
      the PTPN11 gene.
AB  - OBJECTIVE: Noonan syndrome is a clinically homogeneous but genetically
      heterogeneous condition. Type 1 Noonan syndrome is defined by the presence of a
      mutation in the PTPN11 gene, which is found in approximately 40% of the cases.
      Phenotype descriptions and cardiac defects from cohorts with Noonan syndrome were
      delineated in the "pregenomic era." We report the heart defects and links to gene
      dysfunction in cardiac development in a large cohort of patients with type 1
      Noonan syndrome. METHODS: This was a retrospective, multicenter study based on
      clinical history, pictures, and medical and cardiologic workup over time. Data
      were collected by referral geneticists. Mutation screening was performed by
      direct sequencing of exons 2, 3, 4, 7, 8, 12, and 13 and their intron-exon
      boundaries, which harbor 98% of identified mutations the PTPN11 gene. RESULTS: A
      PTPN11 gene mutation was identified in 104 (38.25%) of 274 patients with Noonan
      syndrome. Heart defect was present in 85%. The most prevalent congenital heart
      defects were pulmonary valve stenosis (60%), atrial septal defect, ostium
      secundum type (25%), and stenosis of the peripheral pulmonary arteries (in at
      least 15%). Pulmonary valve stenosis and atrial septal defect, ostium secundum
      type, were significantly associated with the identification of a mutation in the
      PTPN11 gene. Ventricular septal defect and most left-sided heart defects showed a
      trend toward overrepresentation in the group without a mutation. CONCLUSION: We
      compared our data with previous series and integrated the comprehension of
      molecular PTPN11 gene dysfunction in heart development.

PMID- 17515437
TI  - Acute myopericarditis after multiple vaccinations in an adolescent: case report
      and review of the literature.
AB  - We report a case of postvaccination acute myopericarditis in an adolescent. The
      patient presented with acute chest pain, diffuse ST-segment elevation, and
      elevated cardiac enzyme levels. Cardiac MRI was consistent with acute
      myocarditis. He recovered within a few days with nonsteroidal antiinflammatory
      treatment and remains clinically stable, with improvement of MRI findings at the
      10-week follow-up. Postvaccination cases of myopericarditis reported in the
      pediatric literature are also reviewed.

PMID- 17515438
TI  - Auditory brainstem response abnormalities and hearing loss in children with
      craniosynostosis.
AB  - OBJECTIVES: Craniosynostosis is a devastating disorder characterized by premature
      closure of the cranial plates before or shortly after birth. This results in an
      abnormally shaped skull, face, and brain. Little is known about hearing disorders
      in such patients, and nothing has been published about their auditory brainstem
      responses. Our objective was to evaluate such patients for auditory brainstem
      response and hearing disorders with the long-term goal of improving patient
      evaluation and management. PATIENTS AND METHODS: We evaluated the auditory
      brainstem responses, hearing, and brain images of children with fibroblast growth
      factor receptor 2 craniosynostosis (n = 11). RESULTS: Prolongation of the
      auditory brainstem response I-to-III interpeak latency was a frequent
      characteristic of fibroblast growth factor receptor 2 craniosynostosis, occurring
      in 91% of our patients. Prolongation of the III-to-V interpeak latency was an
      occasional characteristic, occurring in 27% of our patients. Whenever the I-to
      III interpeak latency was prolonged, wave II was always abnormal. Associated
      morbidities included sensorineural hearing loss (27%), recurrent otitis media
      (100%), and Arnold-Chiari malformation (27%). Cranial decompression improved the
      interpeak latencies of 2 children. CONCLUSIONS: These previously undocumented
      auditory brainstem response abnormalities reflect abnormal neural transmission,
      which could cause peripheral and central auditory processing disorders. We
      speculate that the major pathogenic basis of the I-to-III interpeak latency and
      wave II abnormalities is compression of the auditory nerve as it passes through
      the internal auditory meatus and posterior fossa, which would explain the
      auditory nerve hearing loss, tinnitus, and vertigo that affect these children.
      Awareness of these abnormalities could lead to important advancements in the
      auditory and neurosurgical assessment and management of this overlooked patient
      group. We provide recommendations for the improved assessment and management of
      these patients. In particular, we recommend that auditory brainstem response
      diagnostics become standard clinical care for this patient group as the best way
      to detect auditory nerve compression.

PMID- 17515439
TI  - Linkage disequilibrium patterns and functional analysis of RGS4 polymorphisms in
      relation to schizophrenia.
AB  - The regulator of G-protein signaling 4 (RGS4, chromosome 1q23.3) plays a critical
      role in G-protein function. Four common single-nucleotide polymorphisms (SNPs)
      localized between the 5' upstream sequence and the first intron, as well as 2
      haplotypes derived from these SNPs may confer liability to schizophrenia (SZ).
      However, the pattern of associations varies among samples. To help clarify the
      putative associations, we report the following analyses: (1) a comprehensive
      catalog of common polymorphisms, (2) linkage disequilibrium (LD) and association
      analyses using these SNPs, and (3) functional analysis based on dual-luciferase
      promoter assays. We identified 62 SNPs from a 20-kb genomic region spanning RGS4,
      of which 26 are common polymorphisms with a minor allele frequency (MAF) of >5%.
      LD analysis suggested 5 clusters of SNPs (r(2) > .8). Association analyses using
      the novel SNPs were consistent with the prior reports, but further localization
      was constrained by significant LD across the region. The 2 haplotypes reported to
      confer liability to SZ had significant promoter activity compared with
      promoterless constructs, suggesting a functional role for both haplotypes.
      Further analyses of promoter sequences are warranted to understand
      transcriptional regulation at RGS4. This information will be useful for further
      analysis of samples in which genetic association of RGS4 polymorphisms with SZ
      has been reported.

PMID- 17515440
TI  - Disorders of thought are severe mood disorders: the selective attention defect in
      mania challenges the Kraepelinian dichotomy a review.
AB  - Kraepelin said severe mental illness was due to 2 diseases subsequently
      characterized as disorders of thought vs disorders of mood, ie, the Kraepelinian
      dichotomy. Schizophrenia, traditionally considered the disorder of thought, has
      been defined by the presence of hallucinations, delusions, catatonia, and
      disorganization. Tangentiality, derailment, loose associations, and thought
      blocking are typically considered pathognomonic of schizophrenia. By contrast,
      the mood disorders have been characterized only as disorders of the emotions,
      though both depression and mania, when severe, are now recognized to include the
      same psychotic features traditionally considered diagnostic of schizophrenia.
      This article addresses disordered thinking in mania in order to clarify the
      relationship between schizophrenia and psychotic mood disorders. Normally, the
      brain's selective attention mechanism filters and prioritizes incoming stimuli by
      excluding from consciousness extraneous, low-priority stimuli and grading the
      importance of more relevant data. Because this "filter/prioritizer" becomes
      defective in mania, tangential stimuli are processed without appropriate
      prioritization. Observed as distractibility, this symptom is an index of the
      breakdown in selective attention and the severity of mania, accounting for the
      signs and symptoms of psychotic thinking. The zone of rarity between
      schizophrenia and psychotic mood disorders is blurred because severe disorders of
      mood are also disorders of thought. This relationship calls into question the
      tenet that schizophrenia is a disease separate from psychotic mood disorders.
      Patients whose case histories are discussed herein gave their written informed
      consent to participate in this institutional human subjects committee-approved
      protocol.

PMID- 17515441
TI  - Intake of fruits and vegetables and polymorphisms in DNA repair genes in bladder
      cancer.
AB  - The objective is to investigate the relationships between fruit and vegetable
      intake, DNA repair gene polymorphisms and the risk of bladder cancer. We have
      analyzed a hospital-based case-control study of 266 individuals with incident,
      histologically confirmed bladder cancer diagnosed between 1994 and 2003. Controls
      (n = 193) were patients treated for benign diseases recruited daily in a random
      fashion from the same hospital as the cases. All cases and controls were
      interviewed face-to-face for major risk factors, along fruit and vegetable
      consumption. Odds ratios (ORs) for fruit and vegetable intake and DNA repair gene
      polymorphisms were adjusted for age and smoking status, using unconditional
      logistic regression. A statistically significant decreased risk was observed for
      fruit and vegetable intake above median (versus below the median) [unadjusted OR
      0.61, confidence interval (CI) 95% 0.50-0.96 and OR 0.54, CI 95% 0.39-0.80,
      respectively]; the decreased risk persisted after adjustment for age and
      cigarette smoking (OR 0.73, CI 95% 0.49-1.01 and OR 0.86, CI 95% 0.56-1.08,
      respectively). The fruits and vegetables associated with decreased risks included
      leafy green vegetables, cruciferous vegetables, apples and citrus fruits. We did
      not find any interactions between DNA repair gene polymorphisms and fruit and
      vegetable intake. This study found a reduced risk associated with fruit and
      vegetable intake. No interaction was observed between fruit and vegetable
      consumption and DNA repair gene polymorphisms.

PMID- 17515442
TI  - Using visual phonics to supplement beginning reading instruction for students who
      are deaf or hard of hearing.
AB  - The purpose of the current study is to expand upon the effectiveness of using
      Visual Phonics in conjunction with Direct Instruction reading programs (B. J.
      Trezek & K. W. Malmgren, 2005; B. J. Trezek & Y. Wang, 2006) and to explore the
      results of utilizing Visual Phonics to supplement another phonics-based reading
      curriculum for students who are deaf or hard of hearing. Twenty students with
      various degrees of hearing loss in kindergarten and first grade as well as 4
      teachers participated in the study. Results of the investigation reveal that,
      given 1 year of instruction from a phonics-based reading curriculum supplemented
      by Visual Phonics, kindergarten and first-grade students who are deaf or hard of
      hearing can demonstrate statistically significant improvements in beginning
      reading skills as measured by standardized assessments.

PMID- 17515443
TI  - Depression in terminal illness: the need for primary care-specific research.
AB  - BACKGROUND: Palliative care research highlights depression as a common, treatable
      condition in patients with terminal cancer. Guidance from the European
      Association for Palliative Care calls for proactive screening and treatment of
      the disease. However, prevalence of depression among primary care patients with
      advanced cancer is unknown and it remains uncertain whether existing guidance is
      appropriate for use by GPs. OBJECTIVE: To estimate the prevalence of depression
      in a primary care population with terminal cancer. METHODS: A two-stage community
      prevalence survey conducted in primary care practices in Merseyside, UK. Adult
      patients with advanced metastatic cancer were invited to join the study. In phase
      1, a depression screening tool (the Edinburgh Depression Scale [EDS]) was used to
      categorize patients as being high or low risk of depression. In phase 2, samples
      from each group underwent a diagnostic assessment using the revised Clinical
      Interview Schedule. Weighted prevalence estimates were calculated. RESULTS: In a
      final sample of 70 (response rate 47.9%), the prevalence of depression was 4.1%
      (95% confidence interval 0-8.8%). The sensitivity and specificity of the EDS were
      poorer than predicted. CONCLUSION: The prevalence of depression in our sample was
      lower than expected given findings from previous studies. Screening tools also
      performed differently in this population. The limitations in our study are
      discussed; however, our findings raise questions about whether depression
      guidance from palliative care studies can be directly applied to a primary care
      setting. We propose the need for development of a primary palliative care
      evidence base to underpin appropriate clinical care.

PMID- 17515445
TI  - Trended cosinor change model for analyzing hemodynamic rhythm patterns in
      hemodialysis patients.
AB  - To describe circadian blood pressure (BP) patterns and linear interdialytic
      changes, a model was developed to describe simultaneously both the straight line
      change and oscillatory variation in BP and heart rate over an interdialytic
      interval in hemodialysis patients. Using this trended cosinor model, we
      simultaneously compared the impact of mean level of BP, linear changes over the
      interdialytic interval, and oscillatory changes in BP and its relationship with
      antihypertensive drug use. Neither a straight-line change model nor the cosinor
      model adequately described the BP variability in 12,750 BP measurements from 136
      chronic stable hemodialysis patients. A combination of the 2 models that allowed
      for the oscillatory rhythmic pattern in BP variation to have an upward trend in
      the interdialytic period most accurately described the data. Time elapsed since
      the end of dialysis demonstrated a better model fit compared with the less
      meaningful clock time. More antihypertensive medication use was associated with
      increasing mean systolic, diastolic, and pulse pressure. Although the rate of
      change was blunted with increasing antihypertensive drug use, the impact on
      oscillatory change was U-shaped for systolic BP, direct for diastolic BP, and
      inverse for pulse pressure. A trended cosinor model better describes the change
      in BP in the interdialytic interval in hemodialysis patients, especially when
      time elapsed is measured from the end of dialysis. Antihypertensive drugs, though
      associated with higher average BP, are associated with blunted rate of change in
      BP over time.

PMID- 17515446
TI  - Metabolic syndrome and early death.

PMID- 17515447
TI  - Acarbose, an alpha-glucosidase inhibitor, attenuates postprandial hypotension in
      autonomic failure.
AB  - Postprandial hypotension is an important clinical condition that predisposes to
      syncope, falls, angina, and cerebrovascular events. The magnitude of the fall in
      blood pressure after meals depends on enteric glucose availability. We
      hypothesized that acarbose, an alpha-glucosidase inhibitor that decreases glucose
      absorption in the small intestine, would attenuate postprandial hypotension.
      Acarbose or placebo was given 20 minutes before a standardized meal in 13
      patients with postprandial hypotension in the setting of autonomic failure (age:
      65+/-2.64 years; body mass index: 25+/-1.08 kg/m(2); supine plasma
      norepinephrine: 110+/-26.6 pg/mL). Four patients were studied in a single-blind
      protocol and 9 patients in a double-blind, randomized, crossover fashion.
      Patients were studied supine, and blood pressure, heart rate, and neuroendocrine
      parameters were obtained at baseline and for 90 minutes after meal intake. After
      adjusting for potential confounders, acarbose significantly attenuated the
      postprandial fall in systolic and diastolic blood pressures by 17 mm Hg (95% CI:
      7 to 28; P=0.003) and 9 mm Hg (95% CI: 5 to 14; P=0.001), respectively.
      Furthermore, acarbose effectively reduced plasma levels of insulin, a known
      vasodilator, by 11 microU/mL (95% CI: 5 to 18; P=0.001) compared with placebo.
      After adjusting for insulin levels, the attenuation of postprandial hypotension
      by acarbose remained significant, indicating that additional mechanisms
      contribute to this effect. In conclusion, 100 mg of acarbose successfully
      improved postprandial hypotension in patients with severe autonomic failure. This
      effect is not explained solely by a reduction in insulin levels.

PMID- 17515448
TI  - Norepinephrine transporter blockade with atomoxetine induces hypertension in
      patients with impaired autonomic function.
AB  - Atomoxetine, a selective norepinephrine transporter blocker, could increase blood
      pressure by elevating norepinephrine concentration in peripheral sympathetic
      neurons. This effect may be masked in healthy subjects by central sympatholytic
      mechanisms. To test this hypothesis we studied the pressor effect of 18 mg of
      atomoxetine (pediatric dose) in 21 patients with damage of the central (10
      subjects) and peripheral (11 subjects) autonomic nervous system. Atomoxetine was
      administered in a randomized, crossover, placebo-controlled fashion, and blood
      pressure and heart rate were measured at baseline and for 60 minutes after drug
      intake. Atomoxetine acutely increased seated and standing systolic blood pressure
      in patients with central autonomic failure by 54+/-26 (mean+/-standard deviation;
      P=0.004) and 45+/-23 mm Hg (P=0.016), respectively, as compared with placebo. At
      the end of the observation period the mean seated systolic blood pressure in the
      atomoxetine group was in the hypertensive range (149+/-26, range 113 to 209 mm
      Hg). However, in patients with peripheral autonomic failure, atomoxetine did not
      elicit a pressor response; seated and standing systolic blood pressure increased
      by 4+/-18 mm Hg (P=0.695) and 0.6+/-8 mm Hg (P=0.546) with atomoxetine as
      compared with placebo. In conclusion, atomoxetine induces a dramatic increase in
      blood pressure in patients with central autonomic failure even at very low doses.
      These findings suggest that a functional central sympatholytic pathway is
      essential to avoid hypertension in patients treated with this drug. Caution
      should be exercised when this medication is used in patients with milder form of
      autonomic impairment.

PMID- 17515449
TI  - Diastolic blood pressure and mortality in the elderly with cardiovascular
      disease.
AB  - Isolated systolic hypertension is predominantly observed in the elderly because
      of increased arterial stiffness. Aggressive treatment leads to excessive lowering
      of diastolic blood pressure and favors the presence of a J-shaped curve
      association with mortality. We investigated whether, in the elderly, this pattern
      of association is a simple epiphenomenon of increased arterial stiffness and
      impaired cardiac function. In a cohort of 331 hospitalized subjects >70 years old
      (mean age+/-SD: 85+/-7 years), aortic pulse wave velocity and pressure wave
      reflections, by pulse wave analysis, and cardiac function, by ultrasound, were
      assessed. During a 2-year follow-up period, 110 subjects died. No association of
      prognosis with systolic pressure, pulse pressure, or pulse wave velocity was
      observed. A J-shaped association between diastolic pressure and overall and
      cardiovascular mortality was observed. Unadjusted Cox regression analysis showed
      that patients in the first tertile of diastolic pressure (< or =60 mm Hg) had
      higher mortality. In Cox regression analysis, diastolic pressure < or =60 mm Hg
      was a predictor of mortality independently from cardiac-vascular properties,
      cardiovascular risk factors, and drug treatment. Multivariate regression analysis
      showed that increased age and low total peripheral resistance, but not left
      ventricular function, were the cardinal determinants of low diastolic pressure.
      An "optimal" diastolic pressure of 70 mm Hg in subjects with isolated systolic
      hypertension was found. We showed that, in the frail elderly, a value of
      diastolic blood pressure < or =60 mm Hg is associated with reduced survival,
      independent from large artery stiffness and left ventricular function, suggesting
      that more rational antihypertensive therapy, not only based on systolic pressure
      level, is needed.

PMID- 17515450
TI  - Role of matrix metalloproteinases in early hypertensive vascular remodeling.
AB  - Hypertension is associated with vascular remodeling characterized by
      rearrangement of extracellular matrix proteins. To evaluate how matrix
      metalloproteinase (MMP)-9 contributes to the progression of hypertensive vascular
      disease in vivo, wild-type (wt) or MMP-9(-/-) mice were treated with angiotensin
      II (Ang II; 1 microg/kg per minute, by minipump) plus a 5% NaCl diet during 10
      days. Baseline blood pressure was equivalent in wt and knockout mice, but Ang II
      treatment increased systolic blood pressure to a greater extent (P<0.05) in MMP
      9(-/-) mice (94+/-6 to 134+/-6 mm Hg; P<0.001) than in wt animals (93+/-4 to
      114+/-6 mm Hg; P<0.01). In wt mice, Ang II treatment increased the carotid artery
      pressure-diameter relationship significantly, and maximal diameter reached 981+/
      19 microm (P<0.01 versus sham; 891+/-10 microm). In contrast, in MMP-9(-/-) mice,
      carotid artery compliance was actually reduced after Ang II (P<0.05), and maximal
      diameter only reached 878+/-13 microm. Ang II treatment induced MMP-2 and
      increased carotid media thickness equally in both phenotypes. However, MMP-9
      induction and in situ gelatinase activity were only enhanced in Ang II-treated wt
      mice, and vessels from these mice also produced more collagen I breakdown
      products than their MMP-9(-/-) counterparts (P<0.05). Inversely, staining for
      collagen IV was particularly enhanced in vessels from MMP-9(-/-) mice treated
      with Ang II. These results demonstrate the following: (1) the onset of Ang II
      induced hypertension is accompanied by increased MMP-9 activity in conductance
      vessels; (2) absence of MMP-9 activity results in vessel stiffness and increased
      pulse pressure; and (3) MMP-9 activation is associated with a beneficial role
      early on in hypertension by preserving vessel compliance and alleviating blood
      pressure increase.

PMID- 17515451
TI  - Emerging roles of antiangiogenic and angiogenic proteins in pathogenesis and
      prediction of preeclampsia.

PMID- 17515452
TI  - Flow-induced remodeling in resistance arteries from obese Zucker rats is
      associated with endothelial dysfunction.
AB  - Chronic increases in blood flow increase arterial diameter and NO-dependent
      dilation in resistance arteries. Because endothelial dysfunction accompanies
      metabolic syndrome, we hypothesized that flow-mediated remodeling might be
      impaired in obese rat resistance arteries. Obese and lean Zucker rat mesenteric
      resistance arteries were exposed to chronic flow increases through arterial
      ligation in vivo: arteries exposed to high flow were compared with normal flow
      arteries. Diameter was measured in vitro in cannulated arteries using pressure
      arteriography. After 7 days, outward remodeling (diameter increased from 346+/-9
      to 412+/-11 mum at 100 mm Hg) occurred in lean high-flow arteries. Endothelium
      dependent tone was reduced in high-flow arteries from obese rats by contrast with
      lean animals. On the other hand, diameter enlargement occurred similarly in the 2
      strains. The involvement of NO in endothelium-dependent dilation (evidenced by NO
      blockade) and endothelial NO synthase phosphorylation was smaller in obese than
      in lean rats. Superoxide anion and reduced nicotinamide-adenine dinucleotide
      phosphate oxidase subunit expression (p67phox and gp91phox) increased in obese
      rats and were higher in high-flow than in control arteries. Acute Tempol (a
      catalase mimetic), catalase plus superoxide dismutase, and l-arginine plus
      tetrahydrobiopterin restored endothelium-dependent dilation in obese rat normal
      and high-flow arteries to the level found in lean control arteries. Thus, flow
      induced remodeling in obese resistance arteries was associated with a reduced
      endothelium-mediated dilation because of a decreased NO bioavailability and an
      excessive superoxide production. This dysfunction might have negative
      consequences in ischemic diseases in patients with obesity or metabolic syndrome.

PMID- 17515453
TI  - Noradrenergic cell specific gene transfer with neuronal nitric oxide synthase
      reduces cardiac sympathetic neurotransmission in hypertensive rats.
AB  - Nitric oxide-cGMP pathway can inhibit cardiac norepinephrine (NE) release.
      Sympathetic hyper-responsiveness in hypertension may result from oxidative stress
      impairing this pathway. We tested the hypothesis that the gene transfer of
      neuronal NO synthase (nNOS) could restore sympathetic balance in the
      spontaneously hypertensive rat (SHR). An adenovirus (5x10(10) particles)
      constructed with a noradrenergic neuron-specific promoter (PRS x8) encoding nNOS
      (Ad.PRS-nNOS) or enhanced green fluorescence protein (Ad.PRS-eGFP) was targeted
      to the right atrial wall by percutaneous injection in age-matched male SHRs and
      Wistar-Kyoto (WKY) rats. Five days after transduction, right atria were removed,
      and evoked [(3)H] norephinephrine (NE) release, NOS activity, and cGMP were
      measured. In the Ad.PRS-eGFP treated group, tissue levels of cGMP were
      significantly lower in the SHR compared with the WKY atria. NE release was also
      greater in the SHR, and soluble guanylate cyclase inhibition did not alter evoked
      [(3)H] NE release in the Ad.PRS-eGFP-treated SHR. All atria treated with Ad.PRS
      nNOS had enhanced nNOS activity when compared with Ad.PRS-eGFP atria. Ad.PRS-nNOS
      in WKY rats reduced NE release compared with the Ad.PRS-eGFP group. Guanylate
      cyclase inhibition enhanced NE release in both Ad.PRS-nNOS- and Ad.PRS-eGFP
      treated WKY atria. Ad.PRS-nNOS restored cGMP levels in the SHR to those seen in
      the WKY atria. In the SHR, Ad.PRS-nNOS also attenuated NE release compared with
      Ad.PRS-eGFP group. This was reversed by guanylate cyclase inhibition. We conclude
      that artificial upregulation of sympathetic nNOS via gene transfer with a
      noradrenergic promoter may provide a novel approach for correcting peripheral
      sympathetic hyperactivity in hypertension.

PMID- 17515454
TI  - Inhibition of Rac1-derived reactive oxygen species in nucleus tractus solitarius
      decreases blood pressure and heart rate in stroke-prone spontaneously
      hypertensive rats.
AB  - Reactive oxygen species (ROS) in the brain are thought to contribute to the
      neuropathogenesis of hypertension by enhancing sympathetic nervous system
      activity. The nucleus tractus solitarius (NTS), which receives afferent input
      from baroreceptors, has an important role in cardiovascular regulation. reduced
      nicotinamide-adenine dinucleotide phosphate oxidase is thought to be a major
      source of ROS in the NTS. Rac1 is a small G protein and a key component of
      reduced nicotinamide-adenine dinucleotide phosphate oxidase. The role of Rac1
      derived ROS in the NTS in cardiovascular regulation of hypertension is unknown.
      Therefore, we examined whether inhibition of Rac1 in the NTS decreases ROS
      generation, thereby reducing blood pressure in stroke-prone spontaneously
      hypertensive rats (SHRSPs). The basal Rac1 activity level in the NTS was greater
      in SHRSPs than in Wistar-Kyoto rats. Inhibition of Rac1, induced by transfecting
      adenovirus vectors encoding dominant-negative Rac1 into the NTS, decreased blood
      pressure, heart rate, and urinary norepinephrine excretion in SHRSPs but not in
      Wistar-Kyoto rats. Inhibition of Rac1 also reduced nicotinamide-adenine
      dinucleotide phosphate oxidase activity and ROS generation. In addition, Cu/Zn
      superoxide dismutase activity in the NTS of SHRSPs was decreased compared with
      that of Wistar-Kyoto rats, despite the increased ROS generation. Overexpression
      of Cu/Zn-superoxide dismutase in the NTS decreased blood pressure and heart rate
      in SHRSPs. These results indicate that the activation of Rac1 in the NTS
      generates ROS via reduced nicotinamide-adenine dinucleotide phosphate oxidase in
      SHRSPs, and this mechanism might be important for the neuropathogenesis of
      hypertension in SHRSPs.

PMID- 17515455
TI  - Sequential changes in antiangiogenic factors in early pregnancy and risk of
      developing preeclampsia.
AB  - Concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin
      (sEng) increase in maternal blood with the approach of clinical preeclampsia.
      Although alterations in these circulating antiangiogenic factors herald the signs
      and symptoms of preeclampsia, in vitro studies suggest they may also play a role
      in regulating early placental cytotrophoblast functions. Early pregnancy changes
      in sFlt1 and sEng may thus identify women destined to develop preeclampsia. We
      performed a nested case-control study of 39 women who developed preeclampsia and
      147 contemporaneous normotensive controls each with serum collected in the first
      (11 to 13 weeks of gestation) and second (17 to 20 weeks) trimesters. Whereas
      levels of sFlt1 and sEng at 11 to 13 weeks were similar between cases and
      controls (sFlt1: 3.5+/-0.3 ng/mL versus 3.0+/-0.1, P=0.14; sEng 6.9+/-0.3 ng/mL
      versus 6.6+/-0.2, P=0.37, respectively), at 17 to 20 weeks both were elevated in
      the women destined to develop preeclampsia (sFlt1: 4.1+/-0.5 ng/mL versus 3.1+/
      0.1, P<0.05; sEng, 6.4+/-0.4 ng/mL versus 5.2+/-0.1, P<0.01). Women who developed
      preterm (<37 weeks) preeclampsia demonstrated even greater sequential changes:
      difference [delta{d}] between second and first trimester levels: dsFlt1, 0.63+/
      0.91 ng/mL in preterm PE versus 0.05+/-0.15 in controls; dsEng, 0.73+/-0.77 ng/mL
      versus -1.32+/-0.18, P<0.01. Similar findings were noted in a cross-sectional
      analysis of specimens collected from the Calcium for Preeclampsia Prevention
      Study. In conclusion, sequential changes in antiangiogenic factors during early
      pregnancy may be useful for predicting preterm preeclampsia.

PMID- 17515456
TI  - Regulation of renin secretion and expression in mice deficient in beta1- and
      beta2-adrenergic receptors.
AB  - The present experiments were performed in beta1/beta2-adrenergic receptor
      deficient mice (beta1/beta2ADR(-/-)) to assess the role of beta-adrenergic
      receptors in basal and regulated renin expression and release. On a control diet,
      plasma renin concentration (in ng angiotensin I per mL per hour), determined in
      tail vein blood, was significantly lower in beta1/beta2ADR(-/-) than in wild-type
      (WT) mice (222+/-65 versus 1456+/-335; P<0.01). Renin content and mRNA were 77%
      and 65+/-5% of WT. Plasma aldosterone (in picograms per mL) was also
      significantly reduced (420+/-36 in beta1/beta2ADR(-/-) versus 692+/-59 in WT). A
      low-salt diet (0.03%) for 1 week increased plasma renin concentration
      significantly in both beta1/beta2ADR(-/-) and WT mice (to 733+/-54 and 2789+/
      555), whereas a high-salt diet (8%) suppressed it in both genotypes (to 85+/-24
      in beta1/beta2ADR(-/-) and to 676+/-213 in WT). The absolute magnitude of salt
      induced changes of plasma renin concentration was markedly greater in WT mice.
      Acute stimulation of renin release by furosemide, quinaprilat, captopril, or
      candesartan caused significant increases of plasma renin concentration in both
      beta1/beta2ADR(-/-) and WT mice, but again the absolute changes were greater in
      WT mice. We conclude that maintenance of normal levels of renin synthesis and
      release requires tonic beta-adrenergic receptor activation. In the chronic
      absence of beta-adrenergic receptor input, the size of the releasable renin pool
      decreases with a concomitant reduction in the magnitude of the plasma renin
      concentration changes caused by variations of salt intake or acute stimulation
      with furosemide, angiotensin-converting enzyme, or angiotensin type 1 receptor
      inhibition, but regulatory responsiveness is nonetheless maintained.

PMID- 17515457
TI  - Relevance of genetics and genomics for prevention and treatment of cardiovascular
      disease: a scientific statement from the American Heart Association Council on
      Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and
      Translational Biology Interdisciplinary Working Group.
AB  - Atherosclerotic cardiovascular disease (CVD) is a major health problem in the
      United States and around the world. Evidence accumulated over decades
      convincingly demonstrates that family history in a parent or a sibling is
      associated with atherosclerotic CVD, manifested as coronary heart disease,
      stroke, and/or peripheral arterial disease. Although there are several mendelian
      disorders that contribute to CVD, most common forms of CVD are believed to be
      multifactorial and to result from many genes, each with a relatively small effect
      working alone or in combination with modifier genes and/or environmental factors.
      The identification and the characterization of these genes and their modifiers
      would enhance prediction of CVD risk and improve prevention, treatment, and
      quality of care. This scientific statement describes the approaches researchers
      are using to advance understanding of the genetic basis of CVD and details the
      current state of knowledge regarding the genetics of myocardial infarction,
      atherosclerotic CVD, hypercholesterolemia, and hypertension. Current areas of
      interest and investigation--including gene-environment interaction,
      pharmacogenetics, and genetic counseling--are also discussed. The statement
      concludes with a list of specific recommendations intended to help incorporate
      usable knowledge into current clinical and public health practice, foster and
      guide future research, and prepare both researchers and practitioners for the
      changes likely to occur as molecular genetics moves from the laboratory to
      clinic.

PMID- 17515458
TI  - Offsetting impact of thrombosis and restenosis on the occurrence of death and
      myocardial infarction after paclitaxel-eluting and bare metal stent implantation.
AB  - BACKGROUND: Drug-eluting stents compared with bare metal stents (BMS) may
      increase late stent thrombosis (ST), although an accompanying increase in the
      rates of death and myocardial infarction (MI) has not been observed. We
      hypothesized that the prevention of restenosis-related adverse events by drug
      eluting stents might offset some or all of the excess risk from ST. METHODS AND
      RESULTS: We analyzed a pooled patient-level database from 4 prospective, double
      blind trials in which 3445 patients were randomized to paclitaxel-eluting stents
      or BMS. The occurrence of death or MI within 7 days of ST or target lesion
      revascularization was assessed. With a median follow-up of 3.2 years, ST occurred
      in 34 patients (1.0%), 31 (91.1%) of whom sustained death or MI within 7 days.
      Target lesion revascularization was performed in 425 patients (12.3%), 15 (3.5%)
      of whom died or had MI within 7 days. ST occurred in 14 BMS and 20 paclitaxel
      eluting stent patients, resulting in 12 and 19 deaths or MIs within 7 days,
      respectively. Target lesion revascularization was performed in 290 BMS and 135
      paclitaxel-eluting stent patients, resulting in 11 and 4 deaths or MI events
      within 7 days, respectively. In total, 23 patients in both the BMS and paclitaxel
      eluting stents groups died or had an MI event within 7 days of either ST or
      target lesion revascularization. CONCLUSIONS: ST, although infrequent, results in
      a high incident rate of death and MI, whereas the more frequent occurrence of
      target lesion revascularization is associated with a finite but lower rate of
      death and MI. The marked reduction in restenosis with drug-eluting stents
      compared with BMS may counterbalance the potential excess risk from late ST with
      drug-eluting stents.

PMID- 17515459
TI  - Clinical reminders attached to echocardiography reports of patients with reduced
      left ventricular ejection fraction increase use of beta-blockers: a randomized
      trial.
AB  - BACKGROUND: Although beta-blockers are known to prolong survival for patients
      with reduced left ventricular ejection fraction, they are often underused. We
      hypothesized that a reminder attached to the echocardiography report would
      increase the use of beta-blockers for patients with reduced left ventricular
      ejection fraction. METHODS AND RESULTS: We randomized 1546 consecutive patients
      with a left ventricular ejection fraction <45% found on echocardiography at 1 of
      3 laboratories to a reminder for use of beta-blockers or no reminder. Patients
      were excluded from analysis if they died within 30 days of randomization (n=89),
      did not receive medications through the Veterans Affairs system after 30 days
      (n=180), or underwent echocardiography at >1 laboratory (n=6). The primary
      outcome was a prescription for an oral beta-blocker between 1 and 9 months after
      randomization. The mean age of the 1271 included patients was 69 years; 60% had a
      history of heart failure, and 51% were receiving treatment with beta-blockers at
      the time of echocardiography. More patients randomized to the reminder had a
      subsequent beta-blocker prescription (74%, 458 of 621) compared with those
      randomized to no reminder (66%, 428 of 650; P=0.002). The effect of the reminder
      was not significantly different for subgroups based on patient location
      (inpatient versus outpatient) or prior use of beta-blockers. CONCLUSIONS: A
      reminder attached to the echocardiography report increased the use of beta
      blockers in patients with depressed left ventricular systolic function.

PMID- 17515460
TI  - Early metoprolol administration before coronary reperfusion results in increased
      myocardial salvage: analysis of ischemic myocardium at risk using cardiac
      magnetic resonance.
AB  - BACKGROUND: Beta-blockers improve clinical outcome when administered early after
      acute myocardial infarction. However, whether beta-blockers actually reduce the
      myocardial infarction size is still in dispute. Cardiac magnetic resonance
      imaging can accurately depict the left ventricular (LV) ischemic myocardium at
      risk (T2-weighted hyperintense region) early after myocardial infarction, as well
      as the extent of necrosis (delayed gadolinium enhancement). The aim of this study
      was to determine whether early administration of metoprolol could increase
      myocardial salvage, measured as the difference between the extent of myocardium
      at risk and myocardial necrosis. METHODS AND RESULTS: Twelve Yorkshire pigs
      underwent a 90-minute left anterior descending coronary occlusion, followed by
      reperfusion. They were randomized to metoprolol (7.5 mg during myocardial
      infarction) or placebo. Global and regional LV function, extent of myocardium at
      risk, and myocardial necrosis were quantified by cardiac magnetic resonance
      imaging studies performed 4 and 22 days after reperfusion in 10 survivors.
      Despite similar extent of myocardium at risk in metoprolol- and placebo-treated
      pigs (30.9% of LV versus 30.6%; P=NS), metoprolol resulted in 5-fold-larger
      salvaged myocardium (32.4% versus 6.2% of myocardium at risk; P=0.015). The LV
      ejection fraction significantly improved in metoprolol-treated pigs between days
      4 and 22 (37.2% versus 43.0%; P=0.037), whereas it remained unchanged in pigs
      treated with placebo (35.1% versus 35.0%; P=NS). The extent of myocardial salvage
      was related directly to LV ejection fraction improvement (P=0.031) and regional
      LV wall motion recovery (P=0.039) at day 22. CONCLUSIONS: Early metoprolol
      administration during acute coronary occlusion increases myocardial salvage. The
      extent of myocardial salvage, measured as the difference between myocardium at
      risk and myocardial necrosis, was associated with regional and global LV motion
      improvement.

PMID- 17515461
TI  - Outcomes and optimal antithrombotic therapy in women undergoing fibrinolysis for
      ST-elevation myocardial infarction.
AB  - BACKGROUND: The manifestations, complications, and outcomes of cardiovascular
      disease differ between women and men. The safety and efficacy of pharmacological
      reperfusion therapy in women with ST-elevation myocardial infarction are of
      particular interest. METHODS AND RESULTS: We investigated outcomes in the
      Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment
      Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, which randomized
      ST-elevation myocardial infarction patients with planned fibrinolysis to
      enoxaparin or unfractionated heparin. Compared with men (n=15,696), women
      (n=4783) were older and more likely to have hypertension and diabetes (P<0.001).
      The unadjusted 30-day mortality rate for women was >2-fold higher than for men
      (13.2% versus 5.4%; odds ratio, 2.66; 95% CI, 2.40 to 2.96). After adjustment for
      age, fibrinolytic therapy, revascularization, region, and elements of the TIMI
      Risk Score, women had a 1.25-fold-higher 30-day risk of death (95% CI, 1.08 to
      1.46) but similar risk of intracerebral hemorrhage (adjusted odds ratio, 0.81;
      95% CI, 0.52 to 1.26). The 30-day rate of death or nonfatal MI in women was
      reduced by enoxaparin compared with unfractionated heparin in women (15.4% versus
      18.3%; P=0.007). Major bleeding was more frequent in women receiving enoxaparin
      compared with those receiving unfractionated heparin (2.3% versus 1.4%; P=0.022)
      but similar among women and men receiving enoxaparin (2.3% versus 2.0%; P=0.39).
      The rates of death, nonfatal myocardial infarction, or nonfatal major bleeding
      (net clinical benefit) were lower with enoxaparin (absolute risk reduction, 2.6%
      in women [P=0.02] and 1.6% in men [P=0.001]). CONCLUSIONS: In ExTRACT-TIMI 25,
      women presented with a profile of higher baseline risk and increased short-term
      mortality. In this large, contemporary clinical trial, women had similar relative
      and greater absolute risk reductions than men when treated with enoxaparin
      compared with unfractionated heparin as adjunctive therapy with fibrinolysis.

PMID- 17515462
TI  - Genetic and shared environmental factors do not confound the association between
      birth weight and hypertension: a study among Swedish twins.
AB  - BACKGROUND: Studies have found associations between low birth weight and
      increased risks of cardiovascular diseases in adulthood. However, these
      associations could be due to confounding by genetic or socioeconomic factors.
      METHODS AND RESULTS: We performed a study on Swedish like-sexed twins with known
      zygosity who were born from 1926 to 1958. First, to obtain an overall effect of
      birth weight on risk of hypertension, we performed cohort analyses on all twins
      (n=16,265). Second, to address genetic and shared environmental confounding, we
      performed a nested co-twin control analysis within 594 dizygotic and 250
      monozygotic twin pairs discordant for hypertension. Birth characteristics,
      including birth weight, were obtained from original birth records. Information
      from adulthood was collected from a postal questionnaire in 1973 (body mass
      index, height, smoking, and alcohol use) and from a telephone interview conducted
      from 1998 to 2002 (hypertension and socioeconomic status). Hypertension was
      defined as reporting both high blood pressure and treatment with antihypertensive
      medication. In the cohort analysis, the adjusted odds ratio for hypertension in
      relation to a 500-g decrease in birth weight was 1.42 (95% confidence interval,
      1.25 to 1.61). In the co-twin control analyses, the corresponding odds ratios
      were 1.34 (95% confidence interval, 1.07 to 1.69) for dizygotic and 1.74 (95%
      confidence interval, 1.13 to 2.70) for monozygotic twins. CONCLUSIONS: In the
      largest twin study on the fetal origins of hypertension, we found that decreased
      birth weight is associated with increased risk of hypertension independently of
      genetic factors, shared familial environment, and risk factors for hypertension
      in adulthood, including body mass index.

PMID- 17515463
TI  - Receptor for activated C-kinase 1, a novel interaction partner of type II bone
      morphogenetic protein receptor, regulates smooth muscle cell proliferation in
      pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by selective
      elevation of pulmonary arterial pressure. The pathological hallmark of PAH is the
      narrowing of pulmonary arterioles secondary to endothelial cell dysfunction and
      smooth muscle cell proliferation. Heterozygous mutations in BMPR2, encoding the
      type II bone morphogenetic protein receptor (BMPRII), were identified in PAH,
      suggesting that alterations to BMPRII function are involved in disease onset
      and/or progression. METHODS AND RESULTS: We identified the receptor for activated
      C-kinase (RACK1) as a novel interaction partner of BMPRII by yeast 2-hybrid
      analyses using the kinase domain of BMPRII as a bait. Glutathione-S-transferase
      pull-down and coimmunoprecipitation confirmed the interaction of RACK1 with
      BMPRII in vitro and in vivo. RACK1-BMPRII interaction was reduced when kinase
      domain mutations occurring in patients with PAH were introduced to BMPRII.
      Immunohistochemistry of lung sections from PAH and control patients and
      immunofluorescence analysis of primary pulmonary arterial smooth muscle cells
      demonstrated colocalization of BMPRII and RACK1 in vivo. Quantitative reverse
      transcription polymerase chain reaction and Western blot analysis showed
      significant downregulation of RACK1 expression in the rat model of monocrotaline
      induced PAH but not in pulmonary arterial smooth muscle cells from PAH patients.
      Abrogation of RACK1 expression in pulmonary arterial smooth muscle cells led to
      decreased Smad1 phosphorylation and increased proliferation, whereas
      overexpression of RACK1 led to increased Smad1 phosphorylation and decreased
      proliferation. CONCLUSIONS: RACK1, a novel interaction partner of BMPRII,
      constitutes a new negative regulator of pulmonary arterial smooth muscle cell
      proliferation, suggesting a potential role for RACK1 in the pathogenesis of PAH.

PMID- 17515464
TI  - B-type natriuretic peptide in low-flow, low-gradient aortic stenosis:
      relationship to hemodynamics and clinical outcome: results from the Multicenter
      Truly or Pseudo-Severe Aortic Stenosis (TOPAS) study.
AB  - BACKGROUND: The prognostic value of B-type natriuretic peptide (BNP) is unknown
      in low-flow, low-gradient aortic stenosis (AS). We sought to evaluate the
      relationship between AS and rest, stress hemodynamics, and clinical outcome.
      METHODS AND RESULTS: BNP was measured in 69 patients with low-flow AS (indexed
      effective orifice area < 0.6 cm2/m2, mean gradient < or = 40 mm Hg, left
      ventricular ejection fraction < or = 40%). All patients underwent dobutamine
      stress echocardiography and were classified as truly severe or pseudosevere AS by
      their projected effective orifice area at normal flow rate of 250 mL/s (effective
      orifice area < or = 1.0 cm2 or > 1.0 cm2). BNP was inversely related to ejection
      fraction at rest (Spearman correlation coefficient r(s)=-0.59, P<0.0001) and at
      peak stress (r(s)=-0.51, P<0.0001), effective orifice area at rest (r(s)=-0.50,
      P<0.0001) and at peak stress (r(s)=-0.46, P=0.0002), and mean transvalvular flow
      (r(s)=-0.31, P=0.01). BNP was directly related to valvular resistance (r(s)=0.42,
      P=0.0006) and wall motion score index (r(s)=0.36, P=0.004). BNP was higher in 29
      patients with truly severe AS versus 40 with pseudosevere AS (median, 743 pg/mL
      [Q1, 471; Q3, 1356] versus 394 pg/mL [Q1, 191 to Q3, 906], P=0.012). BNP was a
      strong predictor of outcome. In the total cohort, cumulative 1-year survival of
      patients with BNP > or = 550 pg/mL was only 47+/-9% versus 97+/-3% with BNP < 550
      (P<0.0001). In 29 patients who underwent valve replacement, postoperative 1-year
      survival was also markedly lower in patients with BNP > or = 550 pg/mL (53+/-13%
      versus 92+/-7%). CONCLUSIONS: BNP is significantly higher in truly severe than
      pseudosevere low-gradient AS and predicts survival of the whole cohort and in
      patients undergoing valve replacement.

PMID- 17515465
TI  - Major hemorrhage and tolerability of warfarin in the first year of therapy among
      elderly patients with atrial fibrillation.
AB  - BACKGROUND: Warfarin is effective in the prevention of stroke in atrial
      fibrillation but is under used in clinical care. Concerns exist that published
      rates of hemorrhage may not reflect real-world practice. Few patients > or = 80
      years of age were enrolled in trials, and studies of prevalent use largely
      reflect a warfarin-tolerant subset. We sought to define the tolerability of
      warfarin among an elderly inception cohort with atrial fibrillation. METHODS AND
      RESULTS: Consecutive patients who started warfarin were identified from January
      2001 to June 2003 and followed for 1 year. Patients had to be > or = 65 years of
      age, have established care at the study institution, and have their warfarin
      managed on-site. Outcomes included major hemorrhage, time to termination of
      warfarin, and reason for discontinuation. Of 472 patients, 32% were > or = 80
      years of age, and 91% had > or = 1 stroke risk factor. The cumulative incidence
      of major hemorrhage for patients > or = 80 years of age was 13.1 per 100 person
      years and 4.7 for those < 80 years of age (P=0.009). The first 90 days of
      warfarin, age > or = 80 years, and international normalized ratio (INR) > or =
      4.0 were associated with increased risk despite trial-level anticoagulation
      control. Within the first year, 26% of patients > or = 80 years of age stopped
      taking warfarin. Perceived safety issues accounted for 81% of them. Rates of
      major hemorrhage and warfarin termination were highest among patients with CHADS2
      scores (an acronym for congestive heart failure, hypertension, age > or = 75,
      diabetes mellitus, and prior stroke or transient ischemic attack) of > or = 3.
      CONCLUSIONS: Rates of hemorrhage derived from younger noninception cohorts
      underestimate the bleeding that occurs in practice. This finding coupled with the
      short-term tolerability of warfarin likely contributes to its underutilization.
      Stroke prevention among elderly patients with atrial fibrillation remains a
      challenging and pressing health concern.

PMID- 17515466
TI  - Congenital heart disease and other heterotaxic defects in a large cohort of
      patients with primary ciliary dyskinesia.
AB  - BACKGROUND: Primary ciliary dyskinesia (PCD) is a recessive genetic disorder that
      is characterized by sinopulmonary disease and reflects abnormal ciliary structure
      and function. Situs inversus totalis occurs in approximately 50% of PCD patients
      (Kartagener's syndrome in PCD), and there are a few reports of PCD with
      heterotaxy (situs ambiguus), such as cardiovascular anomalies. Advances in
      diagnosis of PCD, such as genetic testing, allow the systematic investigation of
      this association. METHODS AND RESULTS: The prevalence of heterotaxic defects was
      determined in 337 PCD patients by retrospective review of radiographic and
      ultrasound data. Situs solitus (normal situs) and situs inversus totalis were
      identified in 46.0% and 47.7% of patients, respectively, and 6.3% (21 patients)
      had heterotaxy. As compared with patients with situs solitus, those with situs
      abnormalities had more ciliary outer dynein arm defects, fewer inner dynein arm
      and central apparatus defects (P<0.001), and more mutations in ciliary outer
      dynein arm genes (DNAI1 and DNAH5; P=0.022). Seven of 12 patients with heterotaxy
      who were genotyped had mutations in DNAI1 or DNAH5. Twelve patients with
      heterotaxy had cardiac and/or vascular abnormalities, and most (8 of 12 patients)
      had complex congenital heart disease. CONCLUSIONS: At least 6.3% of patients with
      PCD have heterotaxy, and most of those have cardiovascular abnormalities. The
      prevalence of congenital heart disease with heterotaxy is 200-fold higher in PCD
      than in the general population (1:50 versus 1:10 000); thus, patients with PCD
      should have cardiac evaluation. Conversely, mutations in genes that adversely
      affect both respiratory and embryological nodal cilia are a significant cause of
      heterotaxy and congenital heart disease, and screening for PCD is indicated in
      those patients.

PMID- 17515467
TI  - Relationship between blood pressure and stroke recurrence in patients with
      intracranial arterial stenosis.
AB  - BACKGROUND: Many clinicians allow blood pressure to run high in patients with
      intracranial stenosis to protect against hypoperfusion. We sought to determine
      whether higher blood pressure decreases the risk of stroke in these patients.
      METHODS AND RESULTS: Data on 567 patients in the Warfarin-Aspirin Symptomatic
      Intracranial Disease (WASID) trial were analyzed. Time to ischemic stroke and
      stroke in the same territory of the stenotic vessel was compared in patients
      grouped by mean systolic blood pressure (SBP) and mean diastolic blood pressure
      (DBP) during the study. Additional analyses were based on severity and location
      of stenosis. Ischemic stroke risk increased with increasing mean SBP and DBP on
      univariate analysis (P<0.0001, P<0.0001) and after adjustment for risk factors
      (P=0.0008, P<0.0001). Elevated mean SBP and DBP also resulted in increased risk
      of stroke in the territory in univariate (P=0.0065, P<0.0001) and adjusted
      (P=0.0002, P=0.0005) analyses. The increased risk of stroke with increasing SBP
      was driven largely by patients in the highest SBP group. Patients with moderate
      (< 70%) stenosis had increased risk of stroke (P<0.0001, P=0.003) and stroke in
      the territory (P=0.0002, P=0.010) with increased SBP and DBP. Patients with
      severe (> or = 70%) stenosis had increased risk of stroke and stroke in the
      territory with elevated DBP (P=0.004, P=0.004). CONCLUSIONS: In patients with
      intracranial stenosis, higher blood pressure is associated with increased (not
      decreased) risk of ischemic stroke and stroke in the territory of the stenotic
      vessel. These findings argue strongly against the common clinical practice of
      maintaining high blood pressure in patients with intracranial stenosis.

PMID- 17515468
TI  - Images in cardiovascular medicine. A magic bullet through the heart.

PMID- 17515469
TI  - Images in cardiovascular medicine. Wolff-Parkinson-White syndrome and atrial
      fibrillation in a patient with a coronary sinus diverticulum.

PMID- 17515470
TI  - Images in cardiovascular medicine. Duration of discharge of neuromuscular
      incapacitating device and inappropriate implantable cardioverter-defibrillator
      detections.

PMID- 17515471
TI  - Letter by Ridker and Everett regarding article, "The inflammatory hypothesis: any
      progress in risk stratification and therapeutic targets?".

PMID- 17515472
TI  - Letter by Wexler and Feldman regarding article, "Ethnic and gender differences in
      ambulatory blood pressure trajectories: results from a 15-year longitudinal study
      in youth and adults".

PMID- 17515473
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- 17515474
TI  - A view from Paris: Nicolas Danchin, MD, FESC. Interview by Robert Short.

PMID- 17515475
TI  - Trials and travails of electrogram-guided ablation of chronic atrial
      fibrillation.

PMID- 17515476
TI  - Clues or miscues? How to make the right interpretation and correctly diagnose
      long-QT syndrome.

PMID- 17515477
TI  - Reevaluation of the volume-outcome relationship for pediatric cardiac surgery.

PMID- 17515478
TI  - Recanalization and stroke outcome.

PMID- 17515479
TI  - Contemporary management of postcatheterization pseudoaneurysms.

PMID- 17515480
TI  - Heparan sulfate proteoglycans at a glance.

PMID- 17515481
TI  - MicroRNAs in human cancer: from research to therapy.
AB  - Numerous miRNAs are deregulated in human cancers, and experimental evidence
      indicates that they can play roles as oncogenes or tumor suppressor genes.
      Similarly to cancer genes that encode proteins, deregulation of miRNA-encoding
      genes is associated with genetic or epigenetic alterations, such as deletions,
      amplifications, point mutations and aberrant DNA methylation. The discovery that
      miRNAs interact with known oncogenes has established further links with molecular
      pathways implicated in malignant transformation. Finally, miRNAs can be used as
      diagnostic markers, and their potential as therapeutic molecules has moved miRNAs
      from the area of basic research to the field of cancer biotechnology.

PMID- 17515482
TI  - Misinterpretation of the fifth vital sign.

PMID- 17515483
TI  - The top 10 reasons why general surgery is a great career.

PMID- 17515484
TI  - Kentucky hepatoma: epidemiologic variant or same problem in a different region?
AB  - BACKGROUND: Hepatitis and cirrhosis are common etiologic factors in
      hepatocellular carcinoma (HCC) in the United States. However, noncirrhotic,
      nonfibrotic HCC has been recognized more frequently in Kentucky. The aim of this
      study was to evaluate the epidemiologic features of this variant of HCC.
      HYPOTHESIS: Kentucky hepatoma, defined as a noncirrhotic, nonfibrotic, hepatitis
      negative HCC, occurs in an older population with more favorable preoperative
      factors when compared with other patients with HCC. DESIGN: A prospective review
      of our 1002 hepatopancreaticobiliary patients, the Kentucky Cancer Registry, and
      the Surveillance, Epidemiology, and End Results database. SETTING: An academic
      referral center. PATIENTS: All patients with HCC treated from January 1, 1999,
      through September 30, 2005, were reviewed for clinicopathologic factors,
      recurrence, and outcome. RESULTS: In a review of the region's 703 patients with
      HCC, we have seen a 4-fold increase in age-specific HCC diagnosis, with the most
      rapid increase seen in the 60- to 69-year-old age group. In our institution's 103
      patients with HCC, 62 (60.2%) were without hepatitis or cirrhosis. These
      noncirrhotic, hepatitis-free patients were found to be significantly older (70 vs
      55 years; P = .001), to be more often female (40.3% vs 24.4%; P = .01), to have a
      larger tumor size (6.5 vs 3.9 cm; P = .004), to have fewer liver lesions (1 vs 3;
      P = .22), and to more frequently undergo surgical therapy (75.6% vs 53.8%; P =
      .01) than the patients with cirrhosis or hepatitis (n = 41). CONCLUSIONS: A
      larger percentage of the patients with HCC seen in our region are significantly
      different from those in other reports throughout the United States in
      preoperative clinical and pathologic presentation. The reason for this change is
      as yet unknown, but the incidence continues to rise annually.

PMID- 17515485
TI  - Evaluating the impact of preoperative breast magnetic resonance imaging on the
      surgical management of newly diagnosed breast cancers.
AB  - HYPOTHESIS: Women with newly diagnosed breast cancers may harbor additional
      ipsilateral or contralateral breast malignancies that are undetected by
      mammography and ultrasonography. Magnetic resonance imaging (MRI) has
      demonstrated excellent sensitivity in the detection of breast cancers. However,
      the impact of routine MRI on the surgical management of new, biopsy-proven breast
      cancers remains unclear. DESIGN: Retrospective analysis of a prospective
      database. SETTING: An academic, tertiary care center in a large metropolitan
      area. PATIENTS: A total of 155 women with breast cancer newly diagnosed by
      mammography, ultrasonography, and needle biopsy underwent preoperative bilateral
      breast MRI in a single-institution, single-surgeon setting during 1 year. MAIN
      OUTCOME MEASURES: Change in surgical management based on breast MRI findings.
      RESULTS: The MRI demonstrated 124 additional suspicious lesions in 73 patients.
      Post-MRI follow-up mammograms or ultrasonograms were required in 65 patients, and
      41 patients underwent additional image-guided biopsies. There was a change in
      surgical management as MRI discovered additional, otherwise undetected
      malignancies in 36 patients based on radiographic-pathologic correlation.
      Lumpectomy was converted to mastectomy in 10 patients (8 beneficial), wider
      excision was performed in 21 patients (10 beneficial), and 5 patients (2
      beneficial) underwent contralateral surgery. Larger tumor size was an independent
      predictor of a beneficial change in surgical management (odds ratio, 1.66; 95%
      confidence interval, 1.04-2.66). CONCLUSIONS: Breast MRI results in a beneficial
      change in surgical management in 9.7% of newly diagnosed breast cancers. The
      detection of additional, otherwise undetected ipsilateral and contralateral
      breast malignancies with MRI suggests that breast MRI may have a role in the
      evaluation of new breast cancers.

PMID- 17515486
TI  - Pancreaticobiliary and duodenal perforations after periampullary endoscopic
      procedures: diagnosis and management.
AB  - OBJECTIVE: To review our experience with management of pancreaticobiliary and
      duodenal (PB/D) perforations after periampullary endoscopic interventions.
      Although pancreaticobiliary and duodenal perforations after periampullary
      endoscopic procedures are rare, their management has not been well described.
      PATIENTS: Individuals who experienced pancreaticobiliary and duodenal
      perforations. MAIN OUTCOME MEASURES: Comorbidities, interventions performed,
      mechanism/site of perforation, management, and hospital morbidity/mortality.
      RESULTS: Seventy-five perforations (0.6%) occurred in 12,427 procedures; 20
      perforations (27%) occurred during biliary stricture dilatation, 18 (24%) during
      diagnostic endoscopic retrograde cholangiopancreatography, and 15 (20%) during
      management of choledocholithiasis. Perforations were caused by guidewire
      insertion in 24 patients (32%), sphincterotomy in 11 (15%), passage of the
      endoscope in 8 (11%), or stent migration in 7 (9%) and were identified during the
      index procedure in 45 patients (60%). Delayed presentations included pain in 33
      patients (44%), leukocytosis in 26 (35%), and/or fever in 13 (17%) and were
      diagnosed using computed tomography in 19 patients (25%) and abdominal
      radiography in 10 (13%); 9 cases (12%) were diagnosed more than 24 hours after
      the procedure. Indications for operative treatment were gaping duodenal
      perforations and perforations in patients with surgically altered anatomy.
      Indications for nonoperative management included contained bile duct perforations
      and focal duodenal perforations. Management was nonoperative in 53 patients (71%)
      and operative in 22 (29%). Patients with duodenal perforations, higher American
      Society of Anesthesia status (P<.01 each), and older age (mean +/- SEM, 65 +/- 4
      vs 55 +/- 2 years; P = .02) were more likely to require operative management.
      Hospital stay (mean +/- SEM, 16 +/- 4 vs 4 +/- 1 days; P<.05) and mortality (13%
      vs 4%; P<.05) were greater in operative patients (P<.05 each). CONCLUSIONS: Most
      (70%) pancreaticobiliary and duodenal perforations secondary to periampullary
      endoscopic interventions can be managed nonoperatively. Most biliary perforations
      can be managed nonoperatively; a requirement for operative treatment increases
      the mortality rate.

PMID- 17515487
TI  - Are 3 sentinel nodes sufficient?
AB  - HYPOTHESIS: It has recently been proposed that only 3 sentinel lymph nodes (SLNs)
      are required for an adequate SLN biopsy. Others have advocated removing all nodes
      that are blue, hot, at the end of a blue lymphatic channel, or palpably
      suspicious or that have radioactive counts of 10% or greater of the most
      radioactive SLN. Our objective was to determine the false-negative rate (FNR)
      associated with limiting SLN biopsy to 3 nodes. DESIGN: Multicenter prospective
      study. SETTING: Both academic and private practice. PATIENTS: A total of 4131
      patients underwent SLN biopsy followed by completion axillary node dissection.
      MAIN OUTCOME MEASURE: The FNR associated with 3-node SLN biopsy. RESULTS: Of the
      4131 patients in this study, an SLN was identified in 3882 (94.0%). The median
      number of SLNs identified was 2; more than 3 SLNs were removed in 738 patients
      (17.9%). Of the patients in whom a SLN was identified, 1358 (35.0%) were node
      positive. The overall FNR in this study was 7.7%. In 89.7% of node-positive
      patients, a positive SLN was found in the first 3 SLNs removed. If SLN biopsy had
      been limited to the first 3 nodes, the FNR would be 10.3% (P = .005 compared with
      removing >3 SLNs). The FNR increased with the strategy of limiting SLN biopsy to
      fewer SLNs (P<.001). CONCLUSION: Removing only 3 SLNs cannot be recommended,
      because it is associated with a substantially increased FNR.

PMID- 17515488
TI  - Length of stay: an appropriate quality measure?
AB  - HYPOTHESIS: Although demographic and clinical information are known to affect
      hospital length of stay (LOS), we hypothesized that LOS after traumatic injury
      would be significantly influenced by nonclinical factors. DESIGN: Retrospective
      database analysis. PATIENTS: Trauma patients treated at hospitals participating
      in data submission to the National Trauma Data Bank. METHODS: The National Trauma
      Data Bank was queried for all patients older than 18 years with an LOS longer
      than 48 hours and complete demographic information including age, sex, and
      race/ethnicity; nonclinical factors including payment type (commercial, Medicaid,
      Medicare, uninsured, and other) and discharge destination (home, rehabilitation
      facility, nursing home, and other); and clinical information (body region
      injured, Injury Severity Score, and Revised Trauma Score). Statistical analysis
      was performed using generalized linear modeling adjusted for multiple
      comparisons. MAIN OUTCOME MEASURES: Length of stay greater than the mean.
      RESULTS: We obtained 313 144 medical records. Mean LOS was 9.6 days. Discharge
      destination had the greatest effect on LOS. Mean LOS for patients with Medicaid
      (11.3 days) was significantly longer than for patients with commercial insurance
      and uninsured patients (each 9.3 days) and patients with Medicare (8.8 days).
      Length of stay was longer for patients discharged to a nursing home (14.2 days)
      or rehabilitation facility (11.5 days) compared with those discharged to any
      other facility (9.6 days). In multivariate analysis, factors significantly
      associated with extended LOS included age, sex, race/ethnicity, insurance status,
      discharge destination, and Revised Trauma Score. CONCLUSIONS: Nonclinical factors
      significantly influence LOS. If LOS is used as a quality measure for injured
      patients, adjustment for these factors is necessary.

PMID- 17515489
TI  - Right hepatectomy for living liver donation vs right hepatectomy for disease:
      intraoperative and immediate postoperative comparison.
AB  - HYPOTHESIS: Perioperative events of patients undergoing living donor (LD) right
      hepatectomy are similar to those of patients undergoing right hepatectomy for
      disease (DZ). DESIGN: Institutional review board-approved retrospective case
      control study. SETTING: Eight hundred-bed tertiary care referral center. PATIENTS
      AND METHODS: We matched 40 patients who had LD with 40 patients who had DZ.
      Perioperative events (anesthesia, surgical events, transfusion, hemodynamic
      events, complications, and length of hospital stay) were compared using the
      signed rank test and exact McNemar test where appropriate. MAIN OUTCOME MEASURES:
      Intraoperative time, transfusion requirements, postoperative complications, and
      hospital length of stay. RESULTS: There was a significant difference in surgical
      time between the LD and DZ groups (median, 4.1 vs 3.3 hours; P = .001). There was
      also a significant difference in anesthesia time between the LD and DZ groups
      (median, 5.6 vs 4.2 hours; P<.001). The level of autologous transfusion was
      higher in the LD group (median, 1.3 vs 0 U in the DZ group; P<.001), and that of
      packed red blood cell transfusion was lower in the LD group (mean, 0 vs 0.5 U; P
      = .008). There was no other significant intraoperative difference. Postoperative
      hemoglobin levels were significantly higher in the LD group (median, 12.6 vs 11.8
      g/dL; P = .03). Comparison of the number of complications in the immediate
      postoperative period revealed no other significant differences. CONCLUSIONS: The
      LD procedure took longer to perform because of the time required for hilar
      dissection. The difference in intraoperative transfusions is attributable to use
      of cell salvage and retransfusion of salvaged blood for all donors; this was not
      routine for DZ procedures. Perioperative outcomes were similar in all other
      respects. The LD procedure has similar outcomes to those of the DZ procedure.

PMID- 17515490
TI  - Behavior and analysis of 36-item Short-Form Health Survey data for surgical
      quality-of-life research.
AB  - HYPOTHESIS: Data from the 36-Item Short-Form Health Survey (SF-36) do not follow
      a normal distribution and should not be analyzed using parametric techniques. A
      novel type of analysis, top-box analysis, may add to the interpretation of these
      data. DESIGN: Review of SF-36 data from preoperative and postoperative patients.
      SETTING: Tertiary care hospital and clinic. PATIENTS: One thousand randomly
      selected preoperative and postoperative patients with a variety of surgical
      diseases completed the SF-36 (8 domains: physical functioning, role physical,
      role emotional, bodily pain, vitality, mental health, social functioning, and
      general health). The best possible score was 100; the worst possible score, 0.
      One item assessed "health transition." The best score was 1; the worst score, 5.
      The health transition item and each domain were analyzed for mean with standard
      deviation, median, mode skewness, kurtosis, and normality. A "top-box" assessment
      was done by determining the frequency of patients scoring 100 in each domain or 1
      in the health transition item. In addition, preoperative and postoperative scores
      were compared. RESULTS: The results for all 1000 questionnaires demonstrated that
      none of the domains had data that followed a normal distribution. The means,
      medians, and modes were different. Five domains had the mode and median at the
      top box. CONCLUSIONS: The SF-36 data did not follow a normal distribution in any
      of the domains. Data were always skewed to the left, with means, medians, and
      modes different. These data need to be statistically analyzed using nonparametric
      techniques. Of the 8 domains, 5 had a significant frequency of top-box scores,
      which also were the domains in which the mode was at 100, implying that change in
      top-box score may be an informative method of presenting change in SF-36 data.

PMID- 17515491
TI  - Practice-based learning and improvement: a curriculum in continuous quality
      improvement for surgery residents.
AB  - HYPOTHESIS: Surgery residents can learn continuous quality improvement (CQI)
      principles within a structured curriculum and propose quality improvement
      projects. DESIGN: Curriculum within a surgical residency program. SETTING: A
      university surgical residency program with multiple hospital training sites.
      PARTICIPANTS: Fifteen surgical residents during the dedicated research year.
      INTERVENTION: A curriculum in CQI that focuses on devising a quality improvement
      project. MAIN OUTCOME MEASURES: Resident self-reported attitudes about quality
      improvement and implementation of resident-initiated quality improvement
      projects. RESULTS: Resident survey data demonstrated an improvement in knowledge,
      self-efficacy, and experiences within CQI. Fifteen individual residents, within
      smaller teams, created 4 quality improvement projects worthy of implementation.
      CONCLUSIONS: A structured CQI curriculum can be successfully integrated into a
      general surgery residency program. Residents can learn the skill of constructing
      CQI project ideas within the framework of the plan-do-study-act cycle. Residents
      are eager to make improvements in their local system of residency. By giving them
      the tools to critically investigate systems improvement and a much needed ear to
      hear their concerns and suggestions for improvement, we found ways to potentially
      enhance patient care and developed ideas to improve the education of future
      surgeons. In doing so, we provided the residents with "buy-in" into their
      residency program, while addressing the competency of practice-based learning and
      improvement required by the Accreditation Council for Graduate Medical Education
      for resident education.

PMID- 17515492
TI  - Image of the month. Internal hernia.

PMID- 17515493
TI  - Image of the month. Perforated schistosomal appendicitis.

PMID- 17515495
TI  - Objective assessment of facial asymmetry in rhinoplasty patients.
AB  - OBJECTIVES: To determine the incidence and nature of facial asymmetry in patients
      referred for consideration of aesthetic rhinoplasty and to assess whether
      objective anthropometric facial measurements correlate with subjective
      perceptions of asymmetry. DESIGN: Two independent observers measured facial
      features, including midline to medial and lateral canthi, tragus, ala, and oral
      commissure distances, in 234 prerhinoplasty surgical photographs. The photographs
      were rated by 10 independent observers for a global "first impression" of facial
      symmetry, and the relationship between anthropometric measurement and subjective
      perception of facial symmetry was explored with logistic regression. RESULTS:
      Objectively, 97% of patients had significant degrees of facial asymmetry, with
      the midline to ala distances showing the most variations and the midline to oral
      commissures showing the least variations. Subjectively, 38% of results were
      perceived as asymmetrical, with the degree of midline to lateral alar margin
      asymmetry being an independent predictor of the perception of facial asymmetry on
      binary logistic regression (P<.003). CONCLUSIONS: A significant correlation was
      found between the degree of objective facial asymmetry, particularly in
      anthropometric nasal measurements, and the subjective perception of a face as
      asymmetrical in patients requesting aesthetic rhinoplasty. This relationship may
      be a factor in patients who request rhinoplasty and should be explored in this
      patient group.

PMID- 17515496
TI  - Direct submentoplasty for neck rejuvenation.
AB  - Facial plastic surgeons commonly see patients with submental laxity and an excess
      of skin and fat in the upper neck. This has colloquially been called the "turkey
      gobbler" deformity. In some cases, this deformity is the patient's only aesthetic
      concern, and full face-lift surgery is not desired. In this study, we reviewed
      the English-language peer-reviewed literature for descriptions of direct
      excisional submentoplasty techniques. Various designs for skin excision and wound
      closure have been used by surgeons over the past several decades. This article
      summarizes the surgical technique as well as the advantages and disadvantages of
      each method. Furthermore, we propose an approach that incorporates many of the
      other designs but to our knowledge has not been described previously in the peer
      reviewed literature. An understanding of these numerous approaches will better
      enable facial plastic surgeons to appropriately address and correct patient
      aesthetic concerns.

PMID- 17515497
TI  - Rehabilitation of long-standing facial nerve paralysis with percutaneous suture
      based slings.
AB  - Long-standing facial paralysis creates significant functional and aesthetic
      problems for patients affected by this deficit. Traditional approaches to correct
      this problem have involved aggressive open procedures such as unilateral face
      lifts and sling procedures using fascia and implantable materials. Unfortunately,
      our results with these techniques over the last 5 years have been suboptimal. The
      traditional face-lift techniques did not address the nasolabial fold to our
      satisfaction, and suture-based techniques alone, while offering excellent short
      term results, failed to provide a long-term solution. This led to the development
      of a novel percutaneous technique combining the minimally invasive approach of
      suture-based lifts with the long-term efficacy of Gore-Tex-based slings. We
      report our results with this technique for static facial suspension in patients
      with long-standing facial nerve paralysis and our surgical outcomes in 13
      patients. The procedure offers re-creation of the nasolabial crease and
      suspension of the oral commissure to its normal anatomic relationships. The
      recovery time is minimal, and the operation is performed as a short outpatient
      procedure. Long-term 2-year follow-up has shown effective preservation of the
      surgical results.

PMID- 17515498
TI  - Influence of botulinum toxin a injection in the practice management of facial
      plastic surgery.

PMID- 17515499
TI  - Placement of a lateral nasal suspension suture via an external rhinoplasty
      approach.

PMID- 17515500
TI  - Jean-Desire-Gustave Courbet's Jo, La Belle Irlandaise.

PMID- 17515501
TI  - Ability of positron emission tomography to detect residual neck node disease in
      patients with head and neck squamous cell carcinoma after definitive
      chemoradiotherapy.
AB  - OBJECTIVE: To report our experience using the neck examination, computed
      tomography (CT), and positron emission tomography (PET) to clinically evaluate
      node-positive patients with head and neck squamous cell cancer for residual neck
      node disease after definitive chemoradiotherapy. DESIGN: Retrospective review of
      all Cleveland Clinic patients with head and neck squamous cell cancer and N2 or
      N3 neck node involvement at presentation who were treated with definitive
      concurrent chemoradiotherapy and who underwent clinical restaging after treatment
      using the neck examination, CT, and PET. SETTING: Tertiary care referral
      institution. PATIENTS: Forty-eight patients with 72 positive necks at diagnosis
      were followed up for a median of 20 months. MAIN OUTCOME MEASURES: Palpable nodes
      on examination, nodes larger than 1 cm, nodes with central necrosis on CT, or any
      hypermetabolic lymph nodes on PET were considered clinical evidence of residual
      nodal disease. The true rate of pathologic involvement was determined by
      histologic examination after planned neck dissection or if regional recurrence
      developed. The sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy were calculated for all 3 clinical assessment
      tools. RESULTS: Planned neck dissection was performed in 33 necks and was
      positive for residual neck node disease in 5 necks. A delayed neck dissection was
      performed in 5 necks and was positive in 3 necks. The positive predictive value
      was low for all 3 clinical assessment tools. The addition of PET did not
      significantly improve the negative predictive value or positive predictive value
      of CT and the clinical examination. CONCLUSIONS: Residual neck node disease after
      definitive chemoradiotherapy was infrequent and was not well predicted by PET. A
      positive PET finding in this setting is of little utility. Although a negative
      PET finding was highly predictive for control of neck disease after
      chemoradiotherapy, it added little to the clinical neck examination and CT.

PMID- 17515502
TI  - Epidemiological features and prognostic factors of cutaneous head and neck
      melanoma: a population-based study.
AB  - OBJECTIVES: To describe the epidemiological features of cutaneous head and neck
      melanoma (CHNM) and to identify factors associated with mortality from this
      disease. DESIGN: A population-based cohort study. SETTING: Patients treated for
      CHNM in Ontario between January 1, 1994, and December 31, 2002, were identified
      through the provincial Cancer Registry. A Cox proportional hazards regression
      model was used to analyze the data. PATIENTS: A total of 2218 patients with CHNM
      were identified, comprising 15.8% of all melanomas in Ontario. The mean age of
      the cohort was 66 years (SD, 16 years); 1363 patients (61.5%) were males. MAIN
      OUTCOME MEASURE: Patients' vital status (dead or alive). RESULTS: The incidence
      of CHNM increased from 2.0 per 100,000 in 1996 to 2.7 per 100,000 in 2001, while
      mortality remained stable. The Cox proportional hazards regression model showed
      that increased age (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.04
      1.06) and male sex (HR, 1.31; 95% CI, 1.03-1.66) had a significantly higher risk
      of death. Patients with lesions of the scalp and neck had a 53% higher risk of
      death than those with lesions of the face. Nodular melanoma (HR, 1.61; 95% CI,
      1.17-2.24) had the worst prognosis compared with other morphological types.
      Increased tumor thickness (HR, 1.05; 95% CI, 1.03-1.07), ulceration (HR, 1.53;
      95% CI, 1.08-2.07), and Clark level V (HR, 1.52; 95% CI, 1.01-2.22) were
      significantly associated with increased mortality. CONCLUSIONS: Our study
      demonstrated an increase in the incidence of CHNM. Advanced age, male sex,
      nodular morphological features, tumor thickness, ulceration, and Clark level V
      carried a significant risk of death, whereas facial melanomas had a favorable
      prognosis.

PMID- 17515503
TI  - Chronic periodontitis and the risk of tongue cancer.
AB  - OBJECTIVE: To assess the association between the history of chronic periodontitis
      and the risk of tongue cancer. DESIGN: Case-control study using preexisting data
      from patients admitted between June 15, 1999, and November 17, 2005. SETTING:
      Department of Dentistry and Maxillofacial Prosthetics at Roswell Park Cancer
      Institute (RPCI), Buffalo, NY. PATIENTS: The cases comprised 51 non-Hispanic
      white men newly diagnosed as having primary squamous cell carcinoma of the
      tongue, and the controls, 54 non-Hispanic white men evaluated during the same
      period but with negative results for malignancy. Children (aged <21 years),
      edentulous or immunocompromised patients, and those with history of any cancer
      were excluded. History of periodontitis was assessed by alveolar bone loss
      measured from panoramic radiographs by 1 examiner blind to cancer status. MAIN
      OUTCOME MEASURE: Incidence of tongue cancer obtained from the RPCI Tumor
      Registry. RESULTS: After adjusting for the effects of age at diagnosis, smoking
      status, and number of teeth, each millimeter of alveolar bone loss was associated
      with a 5.23-fold increase in the risk of tongue cancer (odds ratio, 5.23; 95%
      confidence interval, 2.64-10.35). CONCLUSIONS: This study suggests an association
      between chronic periodontitis and the risk of tongue cancer in men, independent
      of smoking status, age, race, ethnicity, and number of teeth. This association
      needs to be confirmed by larger studies using quantitative assessment of lifetime
      tobacco exposure. If this association is confirmed, it has a potential impact on
      understanding the etiology of oral cancer as well as on its prevention and
      control.

PMID- 17515504
TI  - Comparative genomic instabilities of thyroid and colon cancers.
AB  - OBJECTIVES: To assess the forms and extent of genomic instability in thyroid
      cancers and colorectal neoplasms and to determine if such measurements could
      explain the generally excellent prognosis of thyroid malignant neoplasms compared
      with colon carcinoma. DESIGN: Tumor genome analyses. Genomic instability was
      measured by the following 4 methods, listed in ascending order based on the size
      of events detected: inter-simple sequence repeat polymerase chain reaction (ISSR
      PCR), fractional allelic loss (FAL) analysis, array-based comparative genomic
      hybridization (aCGH), and spectral karyotyping (SKY). RESULTS: The genomic
      instability index of 32 thyroid carcinomas, 59 colon carcinomas, and 11 colon
      polyps was determined by ISSR-PCR; no difference was seen among the 3 groups by
      this method. Fractional allelic loss rates were comparable in thyroid cancers and
      colon polyps and lower than FAL rates in colorectal cancers. Indolent papillary
      thyroid carcinomas were essentially diploid with no large-scale alterations in
      chromosome number or structure when evaluated by aCGH or SKY. In anaplastic
      thyroid cancers, aCGH revealed abundant chromosome alterations. Colorectal
      carcinomas showed extensive copy number changes and chromosomal rearrangements
      when analyzed by aCGH and SKY. CONCLUSIONS: Genomic alterations in papillary
      thyroid carcinoma, such as in benign colon polyps, are principally smaller events
      detected by ISSR-PCR. With the more aggressive tumor types (ie, anaplastic
      thyroid and colorectal carcinomas), larger events detected by FAL analysis, aCGH,
      and SKY were revealed. We hypothesize that mutations caused by smaller genomic
      alterations enable thyroid cells to achieve a minimal malignant phenotype.
      Mutations for aggressive biological behavior appear with larger genomic events.

PMID- 17515505
TI  - Fine-needle aspiration biopsy of the thyroid: atypical cytopathological features.
AB  - OBJECTIVES: To evaluate the positive predictive value of a thyroid nodule being
      malignant when categorized as atypical, and to determine the prognostic
      implications of specific cytopathological features. DESIGN: Retrospective review
      of consecutive patients undergoing thyroid surgery following fine-needle
      aspiration biopsy (FNAB) of thyroid nodules. SETTING: Academic teaching hospital
      in Toronto, Ontario. PATIENTS: A total of 111 consecutive patients with atypical
      findings from an FNAB who underwent thyroid surgery from January 2000 to November
      2005. RESULTS: Of 111 patients included in this study, 62 (56%) were diagnosed
      with a thyroid malignancy on final histopathological examination. The remaining
      49 patients (44%) had benign disease. When comparing patients with a
      postoperative diagnosis of malignancy vs those with benign disease, micronucleoli
      (71% vs 49%; P = .01), nuclear grooves (50% vs 31%; P = .03), and powdery
      chromatin (37% vs 16%; P = .01) were more frequently observed in the group with
      cancer. The probability of malignancy was 83% if all 3 of these features were
      present; 32% if none of these features was present (P = .001). CONCLUSIONS: At
      our institution, when findings from a thyroid nodule FNAB sample were categorized
      as atypical, the positive predictive value of the nodule being malignant was 56%.
      In this series of patients, the presence of micronucleoli, nuclear grooves, and
      powdery chromatin increased the likelihood that an atypical specimen was
      representative of malignant disease. These features may help guide treatment of
      patients with atypical findings from a thyroid nodule FNAB sample.

PMID- 17515506
TI  - The role of human papillomavirus 16 E6 in anchorage-independent and invasive
      growth of mouse tonsil epithelium.
AB  - OBJECTIVE: To provide a manipulatable system to study the mechanism of human
      papillomavirus 16 (HPV16) E6-related transformation of an epithelial cell type
      affected by HPV16 in humans. DESIGN: Biochemical and physiological studies of
      mouse tonsil epithelial cells (MTECs) transformed with HPV16 oncogenes plus H-ras
      in vitro and in vivo. SETTING: Basic research laboratory. PARTICIPANTS: C57BL/6
      mice. INTERVENTIONS: Transduction of the HPV16 oncogenes E6 and E7 in retroviral
      vectors into MTECs with isolation of multiple individual clones that expressed
      E6, E7, or both alone or in conjunction with H-ras. MAIN OUTCOME MEASURES: Growth
      in culture, anchorage-independent growth, and growth in immune competent,
      syngeneic mice. RESULTS: The MTECs that expressed E6 degraded p53 by a mechanism
      that is inhibited by proteasomal blockade. Although normal MTECs senesced after
      20 population doublings, E6 alone or in combination with E7 was sufficient to
      immortalize MTECs beyond 25 population doublings, lower their population-doubling
      time, and permit anchorage-independent growth. However, only MTECs that express
      E6 plus H-ras or E6/E7 plus H-ras formed invasive tumors in immune competent,
      syngeneic mice at orthotopic intraoral and subdermal sites. CONCLUSIONS: We found
      that HPV16 E6 and E7 alone are not sufficient for invasive growth. However, the
      synergistic activity of H-ras and E6 was sufficient to result in invasive growth.

PMID- 17515507
TI  - Association of nuclear, cytoplasmic expression of galectin-3 with beta
      catenin/Wnt-pathway activation in thyroid carcinoma.
AB  - OBJECTIVES: To characterize the localization of galectin-3 in benign and
      malignant thyroid neoplasms and to correlate this with alterations in beta
      catenin and cyclin D1 expression. DESIGN: Immunohistochemical study of 116
      paraffin-embedded archival specimens from 113 patients who had undergone
      thyroidectomy and tissue placed into a commercially available tissue microarray.
      SETTING: Tertiary care hospital. INTERVENTIONS: Thyroid tissue microarrays were
      stained by standard immunohistochemical protocols with monoclonal antibodies
      against galectin-3, beta-catenin, and cyclin D1. MAIN OUTCOME MEASURES: Nuclear
      and cytoplasmic expression of galectin-3 was correlated with clinical parameters,
      beta-catenin, and cyclin D1 expression. RESULTS: Both cytoplasmic (56%) and
      nuclear (42%) galectin-3 expression was observed in most malignant neoplasms but
      was absent in benign thyroid specimens (P<.001). Among carcinomas, cytoplasmic
      galectin-3 expression was observed in papillary thyroid carcinomas (82%) and
      follicular (33%) and medullary (9%) carcinomas but was absent in anaplastic
      carcinomas (P<.001). Galectin-3 nuclear expression was observed in papillary
      thyroid carcinomas (62%) and follicular carcinomas (33%) but was undetectable in
      medullary, anaplastic carcinomas (P<.001). Cytoplasmic but not nuclear galectin-3
      was inversely correlated with American Joint Committee on Cancer TNM stage (P =
      .02). There was a strong correlation between cytoplasmic and nuclear beta-catenin
      expression and both nuclear (P = .04) and cytoplasmic (P = .003) galectin-3
      expression. Similarly, there was a strong association between galectin-3 nuclear
      (P<.001) and cytoplasmic (P<.001) expression and cyclin D1 expression.
      CONCLUSION: Cytoplasmic and nuclear galectin-3 expression seem to be associated
      with activation of the Wnt-signaling pathway in well-differentiated thyroid
      neoplasms, suggesting that galectin-3 plays a role in thyroid carcinogenesis.

PMID- 17515508
TI  - Fractional photothermolysis for the treatment of adult colloid milium.

PMID- 17515509
TI  - Susceptibility to UV-A and UV-B provocation does not correlate with disease
      severity of polymorphic light eruption.
AB  - OBJECTIVE: To examine whether the ease of disease provocation by UV-A and/or UV-B
      radiation correlates with clinical features of polymorphic light eruption (PLE),
      including those indicative of disease severity. DESIGN: Intervention study.
      PATIENTS: One hundred forty-three patients with PLE. INTERVENTIONS: Provocation
      testing with broadband UV-A and UV-B lamps. Additionally, a range of clinical
      characteristics of the disorder, including a 5-item PLE severity score, was
      assessed by questionnaire. MAIN OUTCOME MEASURES: Percentage of PLE rash
      induction by UV-A and UV-B provocation, differences between the skin types, and
      correlation between the results of provocation and a range of clinical
      characteristics of the disorder, including a 5-item PLE severity score. RESULTS:
      Rash provocation was seen in 78.3% of patients after UV-A and in 46.7% after UV-B
      exposure. Neither UV-A nor UV-B provocation showed a significant association with
      the total 5-item severity score. The UV-B reactivity was associated with a high
      score on the severity item "number of months affected per year" (P = .04),
      whereas UV-A responsiveness showed a tendency for association with facial
      involvement (P = .06). CONCLUSION: The objective assessment of UV-A or UV-B
      susceptibility in this large group of patients showed no significant relationship
      with clinical disease severity.

PMID- 17515510
TI  - Improvement of naturally aged skin with vitamin A (retinol).
AB  - OBJECTIVE: To evaluate the effectiveness of topical retinol (vitamin A) in
      improving the clinical signs of naturally aged skin. DESIGN: Randomized, double
      blind, vehicle-controlled, left and right arm comparison study. SETTING: Academic
      referral center. PATIENTS: The study population comprised 36 elderly subjects
      (mean age, 87 years), residing in 2 senior citizen facilities. INTERVENTION:
      Topical 0.4% retinol lotion or its vehicle was applied at each visit by study
      personnel to either the right or the left arm, up to 3 times a week for 24 weeks.
      MAIN OUTCOME MEASURES: Clinical assessment using a semiquantitative scale (0,
      none; 9, most severe) and biochemical measurements from skin biopsy specimens
      obtained from treated areas. RESULTS: After 24 weeks, an intent-to-treat analysis
      using the last-observation-carried-forward method revealed that there were
      significant differences between retinol-treated and vehicle-treated skin for
      changes in fine wrinkling scores (-1.64 [95% CI, -2.06 to -1.22] vs -0.08 [95%
      CI, -0.17 to 0.01]; P<.001). As measured in a subgroup, retinol treatment
      significantly increased glycosaminoglycan expression (P = .02 [n = 6]) and
      procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle.
      CONCLUSIONS: Topical retinol improves fine wrinkles associated with natural
      aging. Significant induction of glycosaminoglycan, which is known to retain
      substantial water, and increased collagen production are most likely responsible
      for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged
      skin is more likely to withstand skin injury and ulcer formation along with
      improved appearance.

PMID- 17515511
TI  - Clinicopathologic correlation of cutaneous metastases: experience from a cancer
      center.
AB  - OBJECTIVE: To analyze the clinical, histopathologic, and immunohistochemical
      characteristics of skin metastases. DESIGN: Retrospective analysis (January 1,
      1990, to December 31, 2005). SETTING: Comprehensive cancer center. PATIENTS:
      Fifty-one patients (21 men and 30 women) with biopsy-proven skin metastases and
      correlative clinical data. INTERVENTIONS: Four dermatopathologists reviewed a
      random mixture of metastases and primary skin tumors. Immunohistochemical studies
      for 12 markers were performed on the metastases, with skin adnexal tumors as
      controls. MAIN OUTCOME MEASURES: Clinical characteristics of cutaneous lesions,
      clinical outcomes, histologic features, and immunohistochemical markers. RESULTS:
      Eighty-six percent (43 of 50) of the patients had known stage IV cancer, and skin
      metastasis was the presenting sign in 12% (6 of 50). In 45% (21 of 47) of the
      biopsies, the lesions were not suspected of being metastases owing to unusual
      clinical presentations. Seventy-six percent of the patients died of disease
      (median survival, 5 months). On pathologic review, many metastases from
      adenocarcinomas were either recognized or suspected, but the primary site was not
      easily identified based on histologic findings alone. Metastases from small cell
      carcinomas and sarcomas were histologically misinterpreted as primary skin
      tumors. Immunohistochemical analysis using a panel including p63, B72.3,
      calretinin, and CK5/6 differentiated metastatic carcinoma from primary skin
      adnexal tumors. CONCLUSIONS: Cutaneous metastases can have variable clinical
      appearances and can mimic benign skin lesions. They are usually seen in patients
      with advanced disease, but they can be the presenting lesion. Although many
      metastatic adenocarcinomas can be recognized based on histologic findings alone,
      immunohistochemical analysis is an important diagnostic adjunct in some cases.

PMID- 17515512
TI  - Retinal toxic reactions following photopheresis.
AB  - BACKGROUND: Extracorporeal photochemotherapy (ECP), also known as photopheresis,
      is a generally well-tolerated therapeutic, immunomodulatory approach successfully
      used in cutaneous T-cell lymphoma and other diseases produced by T-lymphocytes
      such as graft vs host disease. OBSERVATIONS: On 2 separate occasions, a 54-year
      old white man with Sezary syndrome developed cutaneous phototoxic reactions and
      chorioretinitis after being treated with ECP. A pharmacokinetic study showed
      therapeutic blood levels of 8-methoxypsoralen as long as 18 weeks after therapy
      had been terminated. However, the analysis of mutations in genes involved in the
      drug's disposition could not explain these abnormal levels. CONCLUSIONS: To our
      knowledge, there has been no previous description of ECP-related retinal toxic
      effects. This adverse effect was probably linked to impaired drug elimination.
      Further studies would be needed to determine the underlying mechanism.

PMID- 17515513
TI  - Crusted Norwegian scabies in an adult with Langerhans cell histiocytosis: mishaps
      leading to systemic chemotherapy.
AB  - BACKGROUND: Crusted Norwegian scabies is a rare hyperkeratotic variant of scabies
      infestation. We report herein a case of crusted scabies in a woman with
      underlying Langerhans cell histiocytosis (LCH). OBSERVATIONS: A 49-year-old woman
      with LCH was hospitalized owing to marked thrombocytopenia. Her hyperkeratotic
      skin eruption was thought to be secondary to LCH because several years earlier,
      she had positive biopsy findings and had been diagnosed as having LCH. After a 1
      month hospital stay, her laboratory values improved despite worsening of her skin
      lesions. CONCLUSION: Analysis of skin scrapings confirmed the presence of
      scabies, and resolution was achieved with a 1-dose ivermectin treatment.

PMID- 17515514
TI  - Dermoscopic findings in Laugier-Hunziker syndrome.
AB  - BACKGROUND: Laugier-Hunziker syndrome (LHS) is a rare, acquired mucocutaneous
      hyperpigmentation often associated with longitudinal melanonychia. The clinical
      behavior of mucocutaneous pigmented lesions ranges from benign to highly
      malignant. Therefore, in most cases, the clinical diagnosis should be confirmed
      by further diagnostic methods. Dermoscopy is a noninvasive technique that has
      been used to make more accurate diagnoses of pigmented skin lesions.
      Nevertheless, to our knowledge, the dermoscopic features of the pigmented lesions
      in LHS have not been described previously. Herein, we report a case of LHS
      together with its dermoscopic features. OBSERVATIONS: The clinical examination
      revealed macular hyperpigmentation on the oral and genital mucosa, conjunctiva,
      and palmoplantar region together with longitudinal melanonychia. Dermoscopic
      examination of mucosal lesions on the patient's lips and vulva revealed a
      parallel pattern. Longitudinal homogeneous pigmentation was observed on the
      toenails. The pigmented macules on the palms and the sole showed a parallel
      furrow pattern. A skin biopsy sample taken from the labial lesion was compatible
      with a diagnosis of mucosal melanosis. CONCLUSIONS: By means of this case report,
      the dermoscopic features of the pigmented lesions in LHS are described for the
      first time, which facilitates diagnosis with a noninvasive technique. Future
      reports highlighting the dermoscopic features of this syndrome may simplify the
      diagnosis of LHS, which is thought to be underdiagnosed.

PMID- 17515515
TI  - Fluoroscopy-induced chronic radiation skin injury: a disease perhaps often
      overlooked.
AB  - BACKGROUND: Fluoroscopy-induced chronic radiation dermatitis (FICRD) resulting
      from prolonged exposure to ionizing radiation during interventional procedures
      has been documented in the radiology and cardiology literature. However, the
      phenomenon has been rarely reported in the dermatologic literature. Since
      patients with FICRD often see a dermatologist or a primary care physician to
      treat their injuries, the diagnosis of FICRD is perhaps often overlooked.
      OBSERVATIONS: A 62-year-old man with type 2 diabetes mellitus and severe coronary
      artery disease was seen with a 2-year history of a pruritic, tender,
      telangiectatic patch lesion over his left scapula. Over the next 2 years, the
      lesion became indurated and eventually ulcerated. A skin biopsy specimen
      demonstrated changes consistent with a chronic radiation dermatitis. The patient
      was unaware of radiation exposure, but persistent questioning from his
      dermatologists revealed that he had undergone multiple fluoroscopy-guided cardiac
      procedures. This was confirmed by a review of his medical records. CONCLUSION:
      The diagnosis of FICRD should be considered for any patient who is seen with an
      acquired vascular lesion, a morphealike lesion, or an unexplained ulcer localized
      over the scapula, the back, or lateral trunk below the axilla.

PMID- 17515516
TI  - Vitiligo: to treat or not to treat.

PMID- 17515517
TI  - Balneophototherapy for psoriasis using saltwater baths and UV-B irradiation,
      revisited.

PMID- 17515518
TI  - Ulceronecrotic nasoparanasal lesion. Cocaine-induced midline destructive lesions.

PMID- 17515519
TI  - Burgeoning nodule on the scalp of a 65-year-old man. Atypical fibroxanthoma
      (AFX).

PMID- 17515520
TI  - Asymptomatic nodule of the tongue. Cartilaginous choristoma of the tongue.

PMID- 17515521
TI  - Verrucous nodules on the toes of a renal transplant recipient. Cutaneous
      blastomycosis.

PMID- 17515522
TI  - Measuring HRQOL in patients with cutaneous T-cell lymphoma undergoing therapy
      with oral bexarotene and extracorporeal photopheresis.

PMID- 17515523
TI  - Apoptotic responses to all-trans retinoic acid of targretin-resistant, malignant,
      CD4+ peripheral blood T cells from patients with Sezary syndrome.

PMID- 17515524
TI  - Methotrexate and risk for lymphoma.

PMID- 17515525
TI  - Antemortem diagnosis of rabies via nuchal skin biopsy.

PMID- 17515526
TI  - Dermoscopy not yet shown to increase sensitivity of melanoma diagnosis in real
      practice.

PMID- 17515527
TI  - Peristomal pyoderma gangrenosum associated with collagenous colitis.

PMID- 17515528
TI  - Persistent eosinophilia as a presenting sign of scabies in patients with
      disorders of keratinization.

PMID- 17515529
TI  - Ortho-phthalaldehyde causing facial stains after cystoscopy.

PMID- 17515530
TI  - Disseminated cutaneous Kaposi sarcoma and progressive multifocal
      leukoencephalopathy in a patient with idiopathic CD4+ T lymphocytopenia.

PMID- 17515531
TI  - The "louse blouse" as a cause of erythroderma.

PMID- 17515532
TI  - Residency training the neurology resident case log: a national survey of
      neurology residents.

PMID- 17515533
TI  - Teaching video is it III alone, or III and IV?

PMID- 17515535
TI  - Obesity surgery: a word of neurologic caution.

PMID- 17515536
TI  - Tales of Pacific tangles: Cycad exposure and Guamanian neurodegenerative
      diseases.

PMID- 17515537
TI  - Chemotherapy for low-grade gliomas: emerging consensus on its benefits.

PMID- 17515538
TI  - Cycad exposure and risk of dementia, MCI, and PDC in the Chamorro population of
      Guam.
AB  - OBJECTIVE: To study cycad-derived products as possible risk factors for dementia,
      mild cognitive impairment (MCI), and parkinsonism-dementia complex (PDC) on Guam.
      METHODS: Complete risk factor data from in-person interviews of 166 cases of Guam
      dementia, 50 cases of amnestic MCI, and 21 cases of PDC were compared with 1,581
      controls in the base population regarding exposure to cycad-derived products from
      a traditional food (fadang), consumption of fruit bats, and use of cycad-derived
      topical medicine. RESULTS: Adjusted odds ratios (ORs) and 95% CIs for picking,
      processing, and eating fadang in young adulthood ranged from 1.42 (1.05 to 1.91)
      to 2.87 (1.48 to 5.56) and were consistently elevated and significant across all
      three diagnostic outcomes. Associations independent of exposure in young
      adulthood were for picking (OR 0.78, 95% CI 0.64 to 0.96) and processing (OR
      0.77, 95% CI 0.63 to 0.94) fadang in childhood with Guam dementia. Men showed
      stronger and more consistent relations across exposure groups in young adulthood
      compared with women. No associations were found for consumption of fruit bats or
      exposure to cycad used as a topical medicine for any of the outcomes. Estimated
      adjusted population attributable risks suggest that exposure to eating fadang in
      young adulthood incurred the highest attributable risk percent. CONCLUSIONS:
      Environmental lifestyle and diet may contribute to the etiology of
      neurodegenerative diseases in the native population of Guam.

PMID- 17515539
TI  - Prevalence of dementia in Chamorros on Guam: relationship to age, gender,
      education, and APOE.
AB  - OBJECTIVES: To estimate the prevalence of dementia and its clinical subtypes
      among Chamorros on Guam aged 65 years or older and to examine associations with
      age, gender, education, and APOE genotype. BACKGROUND: Chamorros, the indigenous
      people of Guam, had a high incidence of ALS and parkinsonism-dementia complex
      (PDC), in the 1950s. Over the next 50 years, ALS incidence declined markedly, but
      PDC only slightly. The prevalence of late life dementia in Chamorros and its
      relationship to ALS/PDC are unknown. METHODS: Island-wide population-based survey
      of Chamorros aged 65 years or older as of January 1, 2003. Two-stage assessment:
      cognitive and motor screening, followed by neurologic and psychometric
      evaluation. Data were reviewed at consensus conference to make clinical
      diagnoses. RESULTS: Of 2,789 Chamorros aged 65 years or older, 73% were enrolled;
      27% declined participation, died before contact or screening, or moved off Guam.
      The point prevalence of all-cause dementia on February 1, 2004, was 12.2%.
      Prevalence data for subtypes were as follows: Guam dementia (clinically
      equivalent to AD), 8.8%; PDC, 1.5%; pure vascular dementia, 1.3%; other, 0.6%.
      The prevalence of dementia rose exponentially with age. Low education was
      significantly associated with dementia, but gender was not. There was a trend
      toward higher PDC prevalence among men. The APOE epsilon4 allele was not
      associated with dementia. CONCLUSIONS: The prevalence of dementia among elderly
      Chamorros is relatively high. Guam dementia is the most common diagnosis and
      exceeds parkinsonism-dementia complex. Age and low education are strongly
      associated with dementia, but gender and APOE epsilon4 are not. Incidence studies
      will allow risk factors for dementia to be clarified.

PMID- 17515540
TI  - Genotype-phenotype correlation of paroxysmal nonkinesigenic dyskinesia.
AB  - BACKGROUND: Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare disorder
      characterized by episodic hyperkinetic movement attacks. We have recently
      identified mutations in the MR-1 gene causing familial PNKD. METHODS: We reviewed
      the clinical features of 14 kindreds with familial dyskinesia that was not
      clearly induced by movement or during sleep. Of these 14 kindreds, 8 had MR-1
      mutations and 6 did not. RESULTS: Patients with PNKD with MR-1 mutations had
      their attack onset in youth (infancy and early childhood). Typical attacks
      consisted of a mixture of chorea and dystonia in the limbs, face, and trunk, and
      typical attack duration lasted from 10 minutes to 1 hour. Caffeine, alcohol, and
      emotional stress were prominent precipitants. Attacks had a favorable response to
      benzodiazepines, such as clonazepam and diazepam. Attacks in families without MR
      1 mutations were more variable in their age at onset, precipitants, clinical
      features, and response to medications. Several were induced by persistent
      exercise. CONCLUSIONS: Paroxysmal nonkinesigenic dyskinesia (PNKD) should be
      strictly defined based on age at onset and ability to precipitate attacks with
      caffeine and alcohol. Patients with this clinical presentation (which is similar
      to the phenotype initially reported by Mount and Reback) are likely to harbor
      myofibrillogenesis regulator 1 (MR-1) gene mutations. Other "PNKD-like" families
      exist, but atypical features suggests that these subjects are clinically distinct
      from PNKD and do not have MR-1 mutations. Some may represent paroxysmal
      exertional dyskinesia.

PMID- 17515541
TI  - Alcohol consumption, mild cognitive impairment, and progression to dementia.
AB  - OBJECTIVE: To estimate the impact of alcohol consumption on the incidence of mild
      cognitive impairment and its progression to dementia. METHODS: We evaluated the
      incidence of mild cognitive impairment in 1,445 non-cognitively impaired
      individuals and its progression to dementia in 121 patients with mild cognitive
      impairment, aged 65 to 84 years, participating in the Italian Longitudinal Study
      on Aging, with a 3.5-year follow-up. The level of alcohol consumption was
      ascertained in the year before the survey. Dementia and mild cognitive impairment
      were classified using current clinical criteria. RESULTS: Patients with mild
      cognitive impairment who were moderate drinkers, i.e., those who consumed less
      than 1 drink/day (approximately 15 g of alcohol), had a lower rate of progression
      to dementia than abstainers (hazard ratio [HR] 0.15; 95% CI 0.03 to 0.78).
      Furthermore, moderate drinkers with mild cognitive impairment who consumed less
      than 1 drink/day of wine showed a significantly lower rate of progression to
      dementia than abstainers (HR 0.15; 95% CI 0.03 to 0.77). Finally, there was no
      significant association between higher levels of drinking (> or =1 drink/day) and
      rate of progression to dementia in patients with mild cognitive impairment vs
      abstainers. No significant associations were found between any levels of drinking
      and the incidence of mild cognitive impairment in non-cognitively impaired
      individuals vs abstainers. CONCLUSIONS: In patients with mild cognitive
      impairment, up to 1 drink/day of alcohol or wine may decrease the rate of
      progression to dementia.

PMID- 17515542
TI  - Blood-brain barrier impairment in Alzheimer disease: stability and functional
      significance.
AB  - OBJECTIVE: To determine the stability and functional significance of blood-brain
      barrier (BBB) integrity in patients with mild to moderate Alzheimer disease (AD).
      METHODS: Thirty-six patients (mean age 71 +/- 7 years) with mild to moderate AD
      (Mini-Mental State Examination [MMSE] 19 +/- 5) participated in a biomarker study
      involving clinical assessments, brain imaging, and CSF and plasma collection over
      1 year. BBB integrity was assessed with the CSF-albumin index (CSF-AI). RESULTS:
      BBB disruption was present in an important subgroup of patients (n = 8/36, 22%)
      at all time points measured. CSF-AI was highly reproducible over 1 year with an
      intraclass correlation of 0.96. Age, sex, and APOE status did not correlate with
      CSF-AI. Vascular factors (blood pressure, Hachinski ischemia score, MR-derived
      white matter hyperintensity, body mass index) were not strongly associated with
      CSF-AI levels (p = 0.066). CSF/plasma IgG ratio correlated with CSF-AI in a
      manner indicating that peripheral IgG has greater access to the CNS in patients
      with an impaired BBB. Further evidence for the physiologic significance of the
      CSF-AI was noted in the form of correlations with rates of disease progression,
      including annual change on MMSE (r(2) = 0.11, p = 0.023), annual Clinical
      Dementia Rating sum-of-boxes change (r(2) = 0.29, p = 0.001), and annual
      ventricular volume change (r(2) = 0.17, p = 0.007). CONCLUSIONS: Blood-brain
      barrier (BBB) impairment is a stable characteristic over 1 year and present in an
      important subgroup of patients with Alzheimer disease. Age, gender, APOE status,
      vascular risk factors, and baseline Mini-Mental State Examination score did not
      explain the variability in BBB integrity. A role for BBB impairment as a modifier
      of disease progression is suggested by correlations between CSF-albumin index and
      measures of disease progression over 1 year.

PMID- 17515543
TI  - Measles virus-specific plasma cells are prominent in subacute sclerosing
      panencephalitis CSF.
AB  - OBJECTIVE: To demonstrate the specificity of expanded CD138(+) plasma cell clones
      recovered from the CSF of a patient with subacute sclerosing panencephalitis
      (SSPE) for measles virus (MV). METHODS: IgG variable region sequences of single
      antibody-secreting CD138(+) cells sorted from SSPE CSF were amplified by single
      cell PCR and analyzed. Human IgG1 recombinant antibodies (rAbs) were produced
      from four expanded CD138(+) clones and assayed for immunoreactivity against MV
      proteins. RESULTS: Clonal expansion was a prominent feature of the SSPE plasma
      cell repertoire, and each of the four rAbs assayed was specific for either the MV
      fusion or the MV nucleocapsid protein. CONCLUSIONS: Expanded plasma cell clones
      in the CSF of patients with subacute sclerosing panencephalitis produce disease
      relevant antibodies. Recombinant antibodies derived from CSF B cells could
      provide a tool to identify target antigens in idiopathic inflammatory disorders.

PMID- 17515544
TI  - Individual dopaminergic neurons show raised iron levels in Parkinson disease.
AB  - OBJECTIVE: Evidence suggests that abnormal iron metabolism is associated with
      Parkinson disease (PD), with raised iron levels found in pathologically affected
      areas in PD. It is unknown if this elevated iron is actually associated with
      neurons or reactive glia, and we therefore addressed this issue by determining if
      raised iron was present in single dopaminergic neurons. METHODS: We used unfixed
      frozen sections from postmortem tissue of PD patients and elderly normal
      individuals to avoid metal contamination and translocation. Levels of iron and
      other elements were measured using sensitive and specific wavelength dispersive
      electron probe x-ray microanalysis coupled with cathodoluminescence spectroscopy
      in individual substantia nigra dopaminergic neurons. RESULTS: We identified
      raised intraneuronal iron in single defined substantia nigra neurons in PD (mean
      neuronal iron 2,838 vs 1,611, p < 0.0001) but not in other movement disorders
      such as Huntington disease. These findings were unrelated to the density of
      remaining neurons. CONCLUSIONS: Primary changes in neuronal iron could lead to
      neurodegeneration in Parkinson disease.

PMID- 17515545
TI  - Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response
      and outcome.
AB  - OBJECTIVE: To evaluate the predictive impact of chromosome 1p/19q deletions on
      the response and outcome of progressive low-grade gliomas (LGG) treated with up
      front temozolomide (TMZ) chemotherapy. METHODS: Adult patients with measurable,
      progressive LGG (WHO grade II) treated with TMZ delivered at the conventional
      schedule (200 mg/m(2)/day for 5 consecutive days, repeated every 28 days) were
      retrospectively evaluated for response by central review of MRI-s. Chromosome 1p
      and 19q deletions were detected by the loss of the heterozygosity technique
      (LOH). RESULTS: A total of 149 consecutive patients were included in this
      retrospective, single center observational study. The median number of TMZ cycles
      delivered was 14 (range 2 to 30). Seventy-seven patients (53%) experienced an
      objective response (including 22 [15%] cases of partial response and 55 [38%]
      cases of minor response), 55 (37%) patients had stable disease, and 14 (10%) had
      a progressive disease. The median time to maximum tumor response was 12 months
      (range 3 to 30 months). The median progression-free survival (PFS) was 28 months
      (95% CI: 23.4 to 32.6). Material for genotyping was available for 86 patients.
      Combined 1p/19q LOH was present in 42% of the cases and was significantly
      associated with a higher rate (p = 0.02) and longer objective response to
      chemotherapy (p = 0.017), and both longer PFS (p = 4.10(-5)) and overall survival
      (p = 0.04). CONCLUSION: Low-grade gliomas respond to temozolomide and loss of
      chromosome 1p/19q predicts both a durable chemosensitivity and a favorable
      outcome.

PMID- 17515546
TI  - A new locus for autosomal recessive spastic paraplegia (SPG32) on chromosome
      14q12-q21.
AB  - Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders
      characterized by progressive spasticity of the lower limbs. Here, we performed a
      genome-wide linkage analysis on a consanguineous family presenting an autosomal
      recessive form of HSP associated with mild mental retardation, brainstem
      dysraphia, and clinically asymptomatic cerebellar atrophy. We have mapped the
      disease locus SPG32 to chromosome 14q12-q21 within a 30-cM interval, which
      excludes the atlastin gene.

PMID- 17515547
TI  - Report from the Scientific Integrity Advisor: issues arising in 2005 and 2006.

PMID- 17515548
TI  - Neurologic complications of gastric bypass surgery for morbid obesity.
AB  - BACKGROUND: The number of bariatric procedures is rapidly growing as the
      prevalence of obesity in the USA is increasing. Such procedures are not without
      complications, and those affecting the nervous system are often disabling and
      irreversible. We now describe our experience with these complications and review
      the pertinent literature. METHODS: We describe 26 patients with major neurologic
      conditions that seemed causally related to bariatric surgery encountered in the
      neurology service of a tertiary referral university medical center over a decade.
      RESULTS: The neurologic complications affected most regions of the nervous
      system: encephalopathy, optic neuropathy, myelopathy, polyradiculoneuropathy, and
      polyneuropathy. Myelopathy was the most frequent and disabling problem; symptoms
      began about a decade after surgery. Encephalopathy and polyradiculoneuropathy
      were acute and early complications. Except for vitamin B(12) and copper
      deficiencies in patients with myelopathy, we could not correlate specific
      nutritional deficiencies to the neurologic complications. All patients had
      multiple nutritional deficiencies, but their correction did not often yield
      dramatic results. The best result was achieved in one patient after surgical
      revision to reduce the bypassed jejunum. CONCLUSIONS: A wide spectrum of serious
      neurologic conditions may follow bariatric surgery. These complications may occur
      acutely or decades later.

PMID- 17515549
TI  - Obesity, migraine, and chronic migraine: possible mechanisms of interaction.
AB  - Migraine and obesity are associated in several ways. First, both are prevalent
      and disabling disorders influenced by genetic and environmental risk factors.
      Second, migraine with aura, as obesity, seems to be a risk factor for
      cardiovascular events. Finally, large population-based studies suggest that
      obesity is a risk factor for chronic migraine after adjusting for comorbidities.
      In this article, we discuss plausible mechanisms that may account for this
      association. Several of the inflammatory mediators that are increased in obese
      individuals are important in migraine pathophysiology, including interleukins and
      calcitonin gene-related peptide (CGRP). These mediators may increase the
      frequency, severity, and duration of migraine attacks per se, which in turn would
      cause central sensitization. Repeated central sensitization may be associated
      with permanent neuronal damage close to the periaqueductal gray area, with poor
      modulation to pain. Obesity is also a state of sympathetic activation, which may
      contribute to increase in headache frequency. Furthermore, the levels of
      adiponectin are decreased in obesity. At low but not normal levels, adiponectin
      is nociceptive. Shared biologic predisposition may also play a major role.
      Orexins modulate both pain and metabolism. Dysfunction in the orexins pathways
      seems to be a risk factor for both conditions. Finally, conditions that are
      comorbid to both states (e.g., depression, sleep apnea) may also make the
      relationship between both diseases more complex.

PMID- 17515550
TI  - Neurocutaneous melanosis associated with autoimmune diabetes mellitus.

PMID- 17515551
TI  - Lambert-Eaton myasthenic syndrome with pure ocular weakness.

PMID- 17515552
TI  - Atypical clinical course of FXTAS: rapidly progressive dementia as the major
      symptom.

PMID- 17515553
TI  - Reflections: neurology and the humanities. The attic in the rue d'Ulm.

PMID- 17515554
TI  - Thallium intoxication with metallic skin discoloration.

PMID- 17515555
TI  - Is the Canadian health care system better for neurologic care?

PMID- 17515556
TI  - Vascular risk factors and cognitive decline among elderly male twins.

PMID- 17515557
TI  - Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE.

PMID- 17515558
TI  - Multiple myeloma presenting with acute disseminated encephalomyelitis: causal or
      chance link?

PMID- 17515560
TI  - Bloodroot: life stories of nurse practitioners in rural Appalachia.
AB  - This nursing research study was designed to reveal the life stories of nurse
      practitioners in rural Appalachia using storytelling and ballad elements of the
      culture. The researcher was born in a rural Appalachian community in Virginia and
      was summoned to return to the place of her birth, feeling an invisible kinship to
      land, blood ties to family, and a longing to honor rural nursing. Seven nurse
      practitioners from the same community shared their life stories. Using the
      heuristic phenomenological research method of Moustakas, the researcher became
      storyteller. The metaphor of bloodroot emerged as the unity of meaning for the
      life stories. The theme essences were revealed as interconnection: intricate
      patterns of rural Appalachian culture, intertwining relationships,
      interrelationships, and inner journey. "Brand New Home," an Appalachian bluegrass
      ballad, along with pictures of Appalachia, underpins and culminates this study as
      a creative synthesis. Implications for nursing practice, education, and research
      are included.

PMID- 17515562
TI  - Perceptions of health among immigrant Latino adolescents from Mexico.
AB  - PURPOSE: This ethnographic study describes the health-related perceptions of
      immigrant Latino adolescents from Mexico. METHOD: Fourteen adolescents,
      purposively recruited from two non-health-based community settings, participated.
      Each was interviewed twice and completed a visual narrative project using
      disposable cameras. Audiotaped transcripts and photographs were inductively
      analyzed. FINDINGS: Being healthy is holistically perceived by these adolescents
      and includes physical, mental, spiritual, social, and environmental factors.
      Pictures portrayed healthy and unhealthy influences and behaviors, including
      eating habits, exercise, self-care, relationships, garbage, and pollution.
      Personal responsibility was important in being healthy and in promoting one's
      health. Family was identified as an important source of health-related
      information. IMPLICATIONS: Nurses recognizing the holistic, comprehensive health
      related perceptions of immigrant Latino adolescents can promote their health and
      design culturally and developmentally appropriate educational strategies and
      health interventions aimed at eliminating health disparities.

PMID- 17515564
TI  - Nursing home residents' sense of coherence and functional status decline.
AB  - Functional status decline places an enormous burden on health care services and
      strategies to identify at risk subgroups are needed. The purpose of this study
      was to examine the relationship between sense of coherence (SOC) and functional
      status to determine if SOC can be used to identify at-risk subgroups. In a
      convenience sample (N = 65) of nursing home residents measures of functional
      status and SOC were compared at 2 times. The mean functional status score of the
      weak SOC group (n = 28) at Time 1 was 16.14 and 17.32 at Time 2 indicating
      functional status decline. The mean functional status score of the strong SOC
      group (n = 37) at Time 1 was 12.38 and 11.76 at Time 2 indicating improved
      functional status. Although these changes were not statistically significant the
      trends suggest that a weak SOC may indicate increased risk for functional status
      decline.

PMID- 17515566
TI  - Meanings of menopause: cultural influences on perception and management of
      menopause.
AB  - Attitudes and sociocultural perceptions provide the context within which women
      experience menopause. Cultural influences greatly affect how women perceive and
      manage their menopausal symptoms. Cultures may be categorized based on way of
      life, including traditional, immigrant, and modern. Varying perceptions and
      symptom experiences are described, including modifiable and nonmodifiable factors
      that affect the level of distress women feel with menopause. Helping women
      actively participate in management of menopausal symptoms including self-care
      strategies will contribute to feelings of control of menopausal symptoms and
      overall health. By using the highest levels of evidence regarding management of
      menopause, becoming familiar with the cultural and psychosocial influences of
      menopause and then empowering women to make decisions regarding management,
      health care providers can improve their care of perimenopausal and menopausal
      women.

PMID- 17515567
TI  - Effects of holistic nursing course: a paradigm shift for holistic health
      practices.
AB  - A study of an undergraduate course in holistic nursing was conducted to determine
      its impact on personal and professional health care practices. A mixed method
      design was used to examine responses on a sample of 200 participants. Results
      indicated a positive personal impact with continued application of concepts into
      professional health practices. Personal and professional nursing practices were
      influenced from 1 to 7 years after completing the holistic nursing course. After
      introduction of the concepts of self-care and holistic approaches to health,
      students and graduates experienced a shift in values and beliefs related to their
      own health practices. Continued exposure to holistic practices creates a pattern
      of awareness toward health that affects future personal and professional nursing
      practice, creating a paradigm shift for emerging nursing students and graduates
      from the course. This affects the manner in which nurses meet the needs of their
      clients in a variety of settings.

PMID- 17515568
TI  - Exploring improvisation in nursing.
AB  - Improvisation has long been considered a function of music, dance, and the
      theatre arts. An exploration of the definitions and characteristics of this
      concept in relation to the art and practice of nursing provide an opportunity to
      illuminate related qualities within the field of nursing. Nursing has always
      demonstrated improvisation because it is often required to meet the needs of
      patients in a rapidly changing environment. However, little has been done to
      identify improvisation in the practice of nursing or to teach improvisation as a
      nursing knowledge-based skill. This article strives to explore the concept of
      improvisation in nursing, to describe the characteristics of improvisation as
      applied to nursing, and to utilize case studies to illustrate various
      manifestations of improvisation in nursing practice.

PMID- 17515569
TI  - American Society of Clinical Oncology 2007 clinical practice guideline update on
      the role of bisphosphonates in multiple myeloma.
AB  - PURPOSE: To update the recommendations for the use of bisphosphonates in the
      prevention and treatment of bone disease in multiple myeloma. The Update
      Committee expanded the guideline to include a discussion of osteonecrosis of the
      jaw (ONJ). METHODS: For the 2007 update, an Update Committee composed of members
      from the full panel completed a review and analysis of data published since 2002.
      Searches of Medline and the Cochrane Collaboration Library databases were
      performed. RECOMMENDATIONS: For multiple myeloma patients who have, on plain
      radiograph(s) or imaging studies, lytic destruction of bone or spine compression
      fracture from osteopenia, intravenous pamidronate 90 mg delivered over at least 2
      hours or zoledronic acid 4 mg delivered over at least 15 minutes every 3 to 4
      weeks is recommended. Clodronate is an alternative bisphosphonate approved
      worldwide, except in the United States, for oral or intravenous administration.
      New dosing guidelines for patients with pre-existing renal impairment were added
      to the zoledronic acid package insert. Although no similar dosing guidelines are
      available for pamidronate, the Update Committee recommends that clinicians
      consider reducing the initial pamidronate dose in patients with pre-existing
      renal impairment. Zoledronic acid has not been studied in patients with severe
      renal impairment and is not recommended in this setting. The Update Committee
      suggests that bisphosphonate treatment continue for a period of 2 years. At 2
      years, physicians should seriously consider discontinuing bisphosphonates in
      patients with responsive or stable disease, but further use is at the discretion
      of the treating physician. The Update Committee also discusses measures regarding
      ONJ.

PMID- 17515570
TI  - Poor outcome of hormone receptor-positive breast cancer at very young age is due
      to tamoxifen resistance: nationwide survival data in Korea--a report from the
      Korean Breast Cancer Society.
AB  - PURPOSE: Breast cancer in very young women (age < 35 years) is uncommon and
      poorly understood. We sought to evaluate the prognosis and treatment response of
      these patients compared with women ages 35 to 50 years. PATIENTS AND METHODS: We
      analyzed data from 9,885 breast cancer patients age < or = 50 years who were part
      of the Korean Breast Cancer Society registration program between 1992 and 2001.
      The overall survival (OS) and breast cancer-specific survival (BCSS) were
      compared between age groups. RESULTS: One thousand four hundred forty-four
      patients (14.6%) were younger than age 35 and 8,441 (85.4%) patients were between
      35 and 50 years of age. Younger patients had significantly higher T-stage and
      higher lymph node positivity and lower hormone receptor expression than older
      patients. Younger patients had a greater probability of death than older
      patients, regardless of tumor size or lymph node status. The survival difference
      was significant for patients with positive or unknown hormone receptor status (P
      < .0001), but not for patients with negative hormone receptor status. In a
      multivariate analysis, the interaction term of young age and hormone receptor
      positivity was significant for OS and BCSS with a hazard ratio for OS of 2.13
      (95% CI, 1.52 to 2.98). The significant survival benefit from adjuvant hormone
      therapy after chemotherapy observed in older patients (hazard ratio for OS, 0.61;
      95% CI, 0.47 to 0.79; P = .001) could not be seen in younger patients (P > .05).
      CONCLUSION: Younger patients (age < 35) showed worse prognosis than older
      patients (age, 35 to 50 years) only in the hormone receptor-unknown or hormone
      receptor-positive subgroups. Adjuvant tamoxifen therapy might provide less
      survival benefit when added to chemotherapy in very young breast cancer patients.

PMID- 17515571
TI  - Gonadal function in males after chemotherapy for early-stage Hodgkin's lymphoma
      treated in four subsequent trials by the European Organisation for Research and
      Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Etude des Lymphomes de
      l'Adulte.
AB  - PURPOSE: To analyze fertility in male patients treated with various combinations
      of radiotherapy and chemotherapy, with or without alkylating agents, or with
      radiotherapy alone for Hodgkin's lymphoma. PATIENTS AND METHODS: Follicle
      stimulating hormone (FSH) levels were measured in patients with early-stage upper
      diaphragmatic disease enrolled in four European Organisation for Research and
      Treatment of Cancer (EORTC) trials (H6-H9). Median follow-up after therapy was 32
      months. Patients with FSH measurement at least 12 months after end of treatment
      (n = 355) were selected to assess post-treatment fertility. Patients with FSH
      measurement 0 to 9 months after therapy (n = 349) were selected to analyze
      fertility recovery; of these, patients with elevated FSH (> 10 U/L; n = 101) were
      followed until recovery. Factors predictive for therapy-related infertility were
      assessed by logistic regression. RESULTS: The proportion of elevated FSH was 3%
      and 8% in patients treated with radiotherapy only or with nonalkylating
      chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD],
      epirubicin, bleomycin, vinblastine, prednisone [EBVP]); it was 60% (P < .001)
      after chemotherapy containing alkylating agents (mechlorethamine, vincristine,
      procarbazine, prednisone [MOPP], MOPP/doxorubicin, bleomycin, vinblastine [ABV],
      bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine,
      prednisone [BEACOPP]). After a median time of 19 months, recovery of fertility
      occurred in 82% of patients treated without alkylating chemotherapy. This
      proportion was 30%, statistically (P < .001) lower in those treated with
      alkylating chemotherapy, and median time to recovery was 27 months. The post
      treatment proportion of elevated FSH increased significantly (P < .001) with the
      dose of alkylating chemotherapy administered, and recovery was less frequent and
      slower after higher doses. Age more than 50 years and stage II disease also
      contributed to poor outcome. CONCLUSION: Fertility can be secured after
      nonalkylating chemotherapy for Hodgkin's lymphoma. In contrast, alkylating
      chemotherapy has a dismal effect, even after a limited number of cycles.

PMID- 17515572
TI  - Multicenter phase II trial of neoadjuvant therapy with trastuzumab, docetaxel,
      and carboplatin for human epidermal growth factor receptor-2-overexpressing stage
      II or III breast cancer: results of the GETN(A)-1 trial.
AB  - PURPOSE: Trastuzumab plus chemotherapy has become the standard of care for human
      epidermal growth factor receptor-2 (HER-2) -positive breast cancer. Trastuzumab
      based preoperative systemic therapy (PST; neoadjuvant therapy) also appears
      promising, warranting further investigation. PATIENTS AND METHODS: Patients with
      HER-2-positive, stage II/III, noninflammatory, operable breast cancer requiring a
      mastectomy (but who wanted to conserve the breast) received trastuzumab 4 mg/kg
      (day 1), followed by 2 mg/kg weekly, plus docetaxel 75 mg/m2 every 3 weeks, and
      carboplatin (area under curve, 6) for six cycles before surgery. The primary end
      point was pathologic complete response (pCR) rate, determined from surgical
      specimens. RESULTS: Seventy patients were enrolled. Most patients had clinical
      T2/T3 tumors (100%) or clinical N1/2 nodes (53%). Sixty-seven patients (96%)
      completed six cycles of therapy, one patient withdrew due to progressive disease,
      and two patients withdrew for toxicity. A complete or partial objective clinical
      response occurred in 95% of patients (85% and 10%, respectively). Surgery was
      breast conservative in 45 (64%) of 70 patients. In an intent-to-treat analysis,
      tumor and nodal pCR were seen in 27 (39%) of 70 patients. Centralized
      retrospective analysis of HER-2 status demonstrated a 43% pCR rate in the 24 of
      56 confirmed HER-2-overexpressing (3+) and/or fluorescence in situ hybridization
      positive tumors. Treatment was generally well tolerated. Grade 3/4 neutropenia
      and febrile neutropenia were uncommon (2%). Two patients withdrew prematurely due
      to a transient, asymptomatic decrease in left ventricular ejection fraction. No
      symptomatic cardiac dysfunction occurred. CONCLUSION: PST with trastuzumab plus
      docetaxel and carboplatin achieved promising efficacy, with a good pCR rate and
      favorable tolerability in stage II or III HER-2-positive breast cancer.

PMID- 17515573
TI  - Myeloablative therapy with autologous bone marrow transplantation for follicular
      lymphoma at the time of second or subsequent remission: long-term follow-up.
AB  - PURPOSE: The aim of this retrospective analysis was to determine the outcome of
      patients with follicular lymphoma who received myeloablative therapy supported by
      autologous bone marrow transplantation as consolidation of second or subsequent
      remission, with a minimum follow-up of 12 years. PATIENTS AND METHODS: One
      hundred twenty-one adults received cyclophosphamide (CY) and total-body
      irradiation (TBI) supported by autologous bone marrow transplantation, with the
      marrow mononuclear cell fraction having been treated with monoclonal antibodies
      and complement. Data from St Bartholomew's Hospital and Dana-Farber Cancer
      Institute were combined for the purpose of this analysis because the patients
      were treated in an identical manner. RESULTS: Fifty-seven patients are alive, 41
      without progression between 9 and 19 years; 64 patients have died, 20 without
      progression. With a median follow-up of 13.5 years, 60 patients have developed
      recurrent lymphoma. There is an apparent plateau on the remission duration curve
      at 48% at 12 years. Survival of patients treated in second remission was
      significantly longer than the survival of patients treated later in the course of
      the illness. Both remission duration and overall survival were also significantly
      longer for patients treated in second remission compared with an age-matched,
      remission-matched group of patients treated at St Bartholomew's Hospital before
      the introduction of this treatment. However, use of CY+TBI was associated with a
      significant risk of secondary myelodysplasia and secondary acute myeloblastic
      leukemia, resulting in 15 patient deaths. CONCLUSION: These mature data confirm
      that prolonged freedom from recurrence may be achieved with myeloablative therapy
      and that a plateau on the curve seems to emerge with long follow-up.

PMID- 17515574
TI  - Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's
      lymphoma and anaplastic large-cell lymphoma.
AB  - PURPOSE: MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1kappa monoclonal
      antibody that inhibits growth of CD30-expressing tumor cells in preclinical
      models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of
      MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase
      I and II studies were performed. PATIENTS AND METHODS: In the phase I portion,
      MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly
      for 4 weeks to cohorts of three to six patients. Twenty-one patients--16 with
      Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and
      two with CD30+ T-cell lymphoma--were enrolled. Because of the lack of a defined
      MTD or dose-response correlation, the phase II portion was amended to include
      several dose levels. In the phase II portion, an additional 51 patients, 47 with
      HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg. RESULTS:
      MDX-060 was well tolerated, and an MTD has not been identified. Only 7% of
      patients experienced grade 3 or 4 treatment-related adverse events. Among the 72
      patients treated, clinical responses were observed in six. Twenty-five patients
      had stable disease, including five who remained free from progression 1 year
      after treatment. CONCLUSION: MDX-060 was well tolerated at doses up to 15 mg/kg.
      MDX-060 has limited activity as a single agent, but the minimal toxicity observed
      and the significant proportion of patients with stable disease suggests that
      further study of MDX-060 in combination with other therapies is warranted.

PMID- 17515575
TI  - They deserved better.

PMID- 17515576
TI  - HIV microbicide trials halted.

PMID- 17515577
TI  - Family practice a tough sell.

PMID- 17515578
TI  - Imaging possibilities.

PMID- 17515579
TI  - US proposes more stringent conflict-of-interest rules.

PMID- 17515581
TI  - Alternative remuneration.

PMID- 17515582
TI  - Abdominal crunches as an unusual cause of empyema.

PMID- 17515583
TI  - Periorbital and facial swelling due to dermatomyositis.

PMID- 17515584
TI  - Influence of decision aids on patient preferences for anticoagulant therapy: a
      randomized trial.
AB  - BACKGROUND: Decision aids have been shown to be useful in selected situations to
      assist patients in making treatment decisions. Important features such as the
      format of decision aids and their graphic presentation of data on benefits and
      harms of treatment options have not been well studied. METHODS: In a randomized
      trial with a 3 x 2 factorial design, we investigated the effects of decision aid
      format (decision board, decision booklet with audiotape, or interactive computer
      program) and graphic presentation of data (pie graph or pictogram) on patients'
      comprehension and choices of 3 treatments for anticoagulation, identified
      initially as "treatment A" (warfarin), "treatment B" (acetylsalicylic acid) and
      "treatment C" (no treatment). Patients aged 65 years or older without known
      atrial fibrillation and not currently taking warfarin were included. The effect
      of blinding to the treatment name was tested in a before-after comparison. The
      primary outcome was change in comprehension score, as assessed by the Atrial
      Fibrillation Information Questionnaire. Secondary outcomes were treatment choice,
      level of satisfaction with the decision aid, and decisional conflict. RESULTS: Of
      102 eligible patients, 98 completed the study. Comprehension scores (maximum
      score 10) increased by an absolute mean of 3.1 (p < 0.01) after exposure to the
      decision aid regardless of the format or graphic presentation. Overall, 96% of
      the participants felt that the decision aid helped them make their treatment
      choice. Unblinding of the treatment name resulted in 36% of the participants
      changing their initial choice (p < 0.001). INTERPRETATION: The decision aid led
      to significant improvement in patients' knowledge regardless of the format or
      graphic representation of data. Revealing the name of the treatment options led
      to significant shifts in declared treatment preferences.

PMID- 17515585
TI  - Frequency of adverse events in patients with poor anticoagulation: a meta
      analysis.
AB  - BACKGROUND: Patients taking anticoagulants orally over the long term have
      international normalized ratios (INRs) outside the individual therapeutic range
      more than one-third of the time. Improved anticoagulation control will reduce
      hemorrhagic and thromboembolic event rates. To gauge the potential effect of
      improved anticoagulation control, we undertook to determine the proportion of
      anticoagulant-associated events that occur when INRs are outside the therapeutic
      range. METHODS: We conducted a meta-analysis of all studies that assigned
      hemorrhagic and thromboembolic events in patients taking anticoagulants to
      discrete INR ranges. We identified studies using the MEDLINE (1966-2006) and
      EMBASE (1980-2006) databases. We included studies reported in English if the
      majority of patients taking oral anticoagulants had an INR range with a lower
      limit between 1.8 and 2 and an upper limit between 3 and 3.5, and their INR at
      the time of the hemorrhagic or thromboembolic event was recorded. RESULTS: The
      final analysis included results from 45 studies (23 that reported both
      hemorrhages and thromboemboli; 14 that reported hemorrhages only; and 8,
      thromboemboli only) involving a median of 208 patients (limits of interquartile
      range [25th-75th percentile] 131-523 subjects; total n = 71 065). Of these
      studies, 64% were conducted at community practices; the remainder, at
      anticoagulation clinics. About 69% of the studies were classed as having moderate
      or high quality. Overall, 44% (95% confidence interval [CI] 39%-49%) of
      hemorrhages occurred when INRs were above the therapeutic range, and 48% (95% CI
      41%-55%) of thromboemboli took place when below it. The mean proportion of events
      that occurred while the patient's INR was outside the therapeutic range was
      greater for studies with a short mean follow-up (< 1 yr). Between-study
      heterogeneity was significant (p < 0.001). INTERPRETATION: Improved
      anticoagulation control could decrease the likelihood of almost half of all
      anticoagulant-associated adverse events.

PMID- 17515586
TI  - Using decision aids to help patients navigate the "grey zone" of medical decision
      making.

PMID- 17515587
TI  - Teenage pregnancy: trends, contributing factors and the physician's role.

PMID- 17515588
TI  - Septic arthritis in patients with pre-existing inflammatory arthritis.

PMID- 17515589
TI  - Drug-eluting stents.

PMID- 17515590
TI  - Drug-eluting stents.

PMID- 17515593
TI  - Sideways.

PMID- 17515592
TI  - Drug-eluting stents.

PMID- 17515594
TI  - Complex? Regional? Pain? Syndrome?

PMID- 17515595
TI  - Why old people fall (and how to stop them).

PMID- 17515596
TI  - A young man with rapidly progressive multifocal disease affecting the white
      matter.

PMID- 17515597
TI  - Some syndromes of James Ramsay Hunt.

PMID- 17515598
TI  - A neurological MRI menagerie.

PMID- 17515599
TI  - The action potential.

PMID- 17515600
TI  - Neurological letter from... Sierra Leone.

PMID- 17515601
TI  - How good at neurology are you?

PMID- 17515602
TI  - A souvenir from the Pacific Islands.

PMID- 17515603
TI  - The intra-S-phase checkpoint affects both DNA replication initiation and
      elongation: single-cell and -DNA fiber analyses.
AB  - To investigate the contribution of DNA replication initiation and elongation to
      the intra-S-phase checkpoint, we examined cells treated with the specific
      topoisomerase I inhibitor camptothecin. Camptothecin is a potent anticancer agent
      producing well-characterized replication-mediated DNA double-strand breaks
      through the collision of replication forks with topoisomerase I cleavage
      complexes. After a short dose of camptothecin in human colon carcinoma HT29
      cells, DNA replication was inhibited rapidly and did not recover for several
      hours following drug removal. That inhibition occurred preferentially in late-S
      phase, compared to early-S-phase, cells and was due to both an inhibition of
      initiation and elongation, as determined by pulse-labeling nucleotide
      incorporation in replication foci and DNA fibers. DNA replication was actively
      inhibited by checkpoint activation since 7-hydroxystaurosporine (UCN-01), the
      specific Chk1 inhibitor CHIR-124, or transfection with small interfering RNA
      targeting Chk1 restored both initiation and elongation. Abrogation of the
      checkpoint markedly enhanced camptothecin-induced DNA damage at replication sites
      where histone gamma-H2AX colocalized with replication foci. Together, our study
      demonstrates that the intra-S-phase checkpoint is exerted by Chk1 not only upon
      replication initiation but also upon DNA elongation.

PMID- 17515604
TI  - A novel splicing factor, Yju2, is associated with NTC and acts after Prp2 in
      promoting the first catalytic reaction of pre-mRNA splicing.
AB  - The Prp19-associated complex (NTC) is essential for pre-mRNA splicing and is
      associated with the spliceosome during spliceosome activation. NTC is required
      for specifying interactions of U5 and U6 with pre-mRNA to stabilize their
      association with the spliceosome after dissociation of U4. Here, we show that a
      novel splicing factor, Yju2, is associated with components of NTC, and that it is
      required for pre-mRNA splicing both in vivo and in vitro. During spliceosome
      assembly, Yju2 is associated with the spliceosome at nearly the same time as NTC
      but is destabilized after the first catalytic reaction, whereas other NTC
      components remain associated until the reaction is complete. Extracts depleted of
      Yju2 could be complemented by recombinant Yju2, suggesting that Yju2 and NTC are
      not entirely in association with each other. Yju2 is not required for the binding
      of NTC to the spliceosome or for NTC-mediated spliceosome activation.
      Complementation analysis of the affinity-isolated spliceosome formed in Yju2
      depleted extracts demonstrated that Yju2 acts in concert with an unidentified
      heat-resistant factor(s) in an ATP-independent manner to promote the first
      catalytic reaction of pre-mRNA splicing after Prp2-mediated structural
      rearrangement of the spliceosome.

PMID- 17515605
TI  - The 90S preribosome is a multimodular structure that is assembled through a
      hierarchical mechanism.
AB  - The 90S preribosomal particle is required for the production of the 18S rRNA from
      a pre-rRNA precursor. Despite the identification of the protein components of
      this particle, its mechanism of assembly and structural design remain unknown. In
      this work, we have combined biochemical studies, proteomic techniques, and
      bioinformatic analyses to shed light into the rules of assembly of the yeast 90S
      preribosome. Our results indicate that several protein subcomplexes work as
      discrete assembly subunits that bind in defined steps to the 35S pre-rRNA. The
      assembly of the t-UTP subunit is an essential step for the engagement of at least
      five additional subunits in two separate, and mutually independent, assembling
      routes. One of these routes leads to the formation of an assembly intermediate
      composed of the U3 snoRNP, the Pwp2p/UTP-B, subunit and the Mpp10p complex. The
      other assembly route involves the stepwise binding of Rrp5p and the UTP-C
      subunit. We also report the use of a bioinformatic approach that provides a model
      for the topological arrangement of protein components within the fully assembled
      particle. Together, our data identify the mechanism of assembly of the 90S
      preribosome and offer novel information about its internal architecture.

PMID- 17515606
TI  - Bmp2 is critical for the murine uterine decidual response.
AB  - The process of implantation, necessary for all viviparous birth, consists of
      tightly regulated events, including apposition of the blastocyst, attachment to
      the uterine lumen, and differentiation of the uterine stroma. In rodents and
      primates the uterine stroma undergoes a process called decidualization.
      Decidualization, the process by which the uterine endometrial stroma proliferates
      and differentiates into large epithelioid decidual cells, is critical to the
      establishment of fetal-maternal communication and the progression of
      implantation. The role of bone morphogenetic protein 2 (Bmp2) in regulating the
      transformation of the uterine stroma during embryo implantation in the mouse was
      investigated by the conditional ablation of Bmp2 in the uterus using the (PR-cre)
      mouse. Bmp2 gene ablation was confirmed by real-time PCR analysis in the PR-cre;
      Bmp2fl/fl (termed Bmp2d/d) uterus. While littermate controls average 0.9 litter
      of 6.2+/-0.7 pups per month, Bmp2d/d females are completely infertile. Analysis
      of the infertility indicates that whereas embryo attachment is normal in the
      Bmp2d/d as in control mice, the uterine stroma is incapable of undergoing the
      decidual reaction to support further embryonic development. Recombinant human
      BMP2 can partially rescue the decidual response, suggesting that the observed
      phenotypes are not due to a developmental consequence of Bmp2 ablation.
      Microarray analysis demonstrates that ablation of Bmp2 leads to specific gene
      changes, including disruption of the Wnt signaling pathway, Progesterone receptor
      (PR) signaling, and the induction of prostaglandin synthase 2 (Ptgs2). Taken
      together, these data demonstrate that Bmp2 is a critical regulator of gene
      expression and function in the murine uterus.

PMID- 17515607
TI  - noxin, a novel stress-induced gene involved in cell cycle and apoptosis.
AB  - We describe a novel stress-induced gene, noxin, and a knockout mouse line with an
      inactivated noxin gene. The noxin gene does not have sequelogs in the genome and
      encodes a highly serine-rich protein with predicted phosphorylation sites for
      ATM, Akt, and DNA-dependent protein kinase kinases; nuclear localization signals;
      and a Zn finger domain. noxin mRNA and protein levels are under tight control by
      the cell cycle. noxin, identified as a nitric oxide-inducible gene, is strongly
      induced by a wide range of stress signals: gamma- and UV irradiation, hydrogen
      peroxide, adriamycin, and cytokines. This induction is dependent on p53. Noxin
      accumulates in the nucleus in response to stress and, when ectopically expressed,
      Noxin arrests the cell cycle at G1; although it also induces p53, the cell cycle
      arrest function of Noxin is independent of p53 activity. noxin knockout mice are
      viable and fertile; however, they have an enlarged heart, several altered
      hematopoietic parameters, and a decreased number of spermatids. Importantly, loss
      or downregulation of Noxin leads to increased cell death. Our results suggest
      that Noxin may be a component of the cell defense system: it is activated by
      various stress stimuli, helps cells to withdraw from cycling, and opposes
      apoptosis.

PMID- 17515608
TI  - Interchromosomal crossover in human cells is associated with long gene conversion
      tracts.
AB  - Crossovers have rarely been observed in specific association with
      interchromosomal gene conversion in mammalian cells. In this investigation two
      isogenic human B-lymphoblastoid cell lines, TI-112 and TSCER2, were used to
      select for I-SceI-induced gene conversions that restored function at the
      selectable thymidine kinase locus. Additionally, a haplotype linkage analysis
      methodology enabled the rigorous detection of all crossover-associated
      convertants, whether or not they exhibited loss of heterozygosity. This
      methodology also permitted characterization of conversion tract length and
      structure. In TI-112, gene conversion tracts were required to be complex in tract
      structure and at least 7.0 kb in order to be selectable. The results demonstrated
      that 85% (39/46) of TI-112 convertants extended more than 11.2 kb and 48% also
      exhibited a crossover, suggesting a mechanistic link between long tracts and
      crossover. In contrast, continuous tracts as short as 98 bp are selectable in
      TSCER2, although selectable gene conversion tracts could include a wide range of
      lengths. Indeed, only 16% (14/95) of TSCER2 convertants were crossover
      associated, further suggesting a link between long tracts and crossover. Overall,
      these results demonstrate that gene conversion tracts can be long in human cells
      and that crossovers are observable when long tracts are recoverable.

PMID- 17515609
TI  - Prolonged Sox4 expression in oligodendrocytes interferes with normal myelination
      in the central nervous system.
AB  - The highly related transcription factors Sox4 and Sox11 are both expressed in
      oligodendrocyte precursors. Yet whether they have a function in oligodendrocyte
      development is unknown. By overexpressing Sox4 under the control of 3.1 kb of 5'
      flanking sequences of the myelin basic protein gene in transgenic mice, we
      extended Sox4 expression in the oligodendrocyte lineage from oligodendrocyte
      precursors to cells undergoing terminal differentiation. As a consequence of
      transgene expression, mice develop the full spectrum of phenotypic traits
      associated with a severe hypomyelination during the first postnatal weeks. Myelin
      gene expression was severely reduced, and myelin dramatically thinned in several
      central nervous system (CNS) regions. Despite these disturbances in CNS
      myelination, the number of oligodendrocytic cells remained unaltered. Considering
      that apoptosis rates were normal and proliferation only slightly increased,
      oligodendrocytes likely persist in a premyelinating to early myelinating state.
      This shows that prolonged Sox4 expression in cells of the oligodendrocyte lineage
      is incompatible with the acquisition of a fully mature phenotype and argues that
      the presence of Sox4, and possibly Sox11, in oligodendrocyte precursors may
      normally prevent premature differentiation.

PMID- 17515610
TI  - p53 mediates senescence-like arrest induced by chronic replicational stress.
AB  - Previous studies have shown that exposure of cells to high levels of
      replicational stress leads to permanent proliferation arrest that does not
      require p53. We have examined cellular responses to therapeutically relevant low
      levels of replicational stress that allow limited proliferation. Chronic exposure
      to low concentrations of hydroxyurea, aphidicolin, or etoposide induced
      irreversible cell cycle arrest after several population doublings. Inhibition of
      p53 activity antagonized this arrest and enhanced the long-term proliferation of
      p53 mutant cells. p21CIP1 was found to be a critical p53 target for arrest
      induced by hydroxyurea or aphidicolin, but not etoposide, as judged by the
      ability of p21CIP1 suppression to mimic the effects of p53 disruption.
      Suppression of Rad51 expression, required for homologous recombination repair,
      blocked the ability of mutant p53 to antagonize arrest induced by etoposide, but
      not aphidicolin. Thus, the ability of mutant p53 to prevent arrest induced by
      replicational stress per se is primarily dependent on preventing p21CIP1 up
      regulation. However, when replication stress is associated with DNA strand breaks
      (such as with etoposide), up-regulation of homologous recombination repair in
      response to p53 disruption becomes important. Since replicational stress leads to
      clonal selection of cells with p53 mutations, our results highlight the potential
      importance of chronic replicational stress in promoting cancer development.

PMID- 17515611
TI  - Epigenetic regulation of tumor necrosis factor alpha.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a potent cytokine which regulates
      inflammation via the induction of adhesion molecules and chemokine expression.
      Its expression is known to be regulated in a complex manner with transcription,
      message turnover, message splicing, translation, and protein cleavage from the
      cell surface all being independently regulated. This study examined both cell
      lines and primary cells to understand the developmental regulation of epigenetic
      changes at the TNF-alpha locus. We demonstrate that epigenetic modifications of
      the TNF-alpha locus occur both developmentally and in response to acute
      stimulation and, importantly, that they actively regulate expression. DNA
      demethylates early in development, beginning with the hematopoietic stem cell.
      The TNF-alpha locus migrates from heterochromatin to euchromatin in a progressive
      fashion, reaching euchromatin slightly later in differentiation. Finally, histone
      modifications characteristic of a transcriptionally competent gene occur with
      myeloid differentiation and progress with differentiation. Additional histone
      modifications characteristic of active gene expression are acquired with
      stimulation. In each case, manipulation of these epigenetic variables altered the
      ability of the cell to express TNF-alpha. These studies demonstrate the
      importance of epigenetic regulation in the control of TNF-alpha expression. These
      findings may have relevance for inflammatory disorders in which TNF-alpha is
      overproduced.

PMID- 17515612
TI  - Genomic analyses of transcription factor binding, histone acetylation, and gene
      expression reveal mechanistically distinct classes of estrogen-regulated
      promoters.
AB  - To explore the global mechanisms of estrogen-regulated transcription, we used
      chromatin immunoprecipitation coupled with DNA microarrays to determine the
      localization of RNA polymerase II (Pol II), estrogen receptor alpha (ERalpha),
      steroid receptor coactivator proteins (SRC), and acetylated histones H3/H4 (AcH)
      at estrogen-regulated promoters in MCF-7 cells with or without estradiol (E2)
      treatment. In addition, we correlated factor occupancy with gene expression and
      the presence of transcription factor binding elements. Using this integrative
      approach, we defined a set of 58 direct E2 target genes based on E2-regulated Pol
      II occupancy and classified their promoters based on factor binding, histone
      modification, and transcriptional output. Many of these direct E2 target genes
      exhibit interesting modes of regulation and biological activities, some of which
      may be relevant to the onset and proliferation of breast cancers. Our studies
      indicate that about one-third of these direct E2 target genes contain promoter
      proximal ERalpha-binding sites, which is considerably more than previous
      estimates. Some of these genes represent possible novel targets for regulation
      through the ERalpha/AP-1 tethering pathway. Our studies have also revealed
      several previously uncharacterized global features of E2-regulated gene
      expression, including strong positive correlations between Pol II occupancy and
      AcH levels, as well as between the E2-dependent recruitment of ERalpha and SRC at
      the promoters of E2-stimulated genes. Furthermore, our studies have revealed new
      mechanistic insights into E2-regulated gene expression, including the absence of
      SRC binding at E2-repressed genes and the presence of constitutively bound,
      promoter-proximally paused Pol IIs at some E2-regulated promoters. These
      mechanistic insights are likely to be relevant for understanding gene regulation
      by a wide variety of nuclear receptors.

PMID- 17515614
TI  - Communicating the benefits of breast feeding.

PMID- 17515613
TI  - Myosin 5a is an insulin-stimulated Akt2 (protein kinase Bbeta) substrate
      modulating GLUT4 vesicle translocation.
AB  - Phosphatidylinositol 3-kinase activation of Akt signaling is critical to insulin
      stimulated glucose transport and GLUT4 translocation. However, the downstream
      signaling events following Akt activation which mediate glucose transport
      stimulation remain relatively unknown. Here we identify an Akt consensus
      phosphorylation motif in the actin-based motor protein myosin 5a and show that
      insulin stimulation leads to phosphorylation of myosin 5a at serine 1650. This
      Akt-mediated phosphorylation event enhances the ability of myosin 5a to interact
      with the actin cytoskeleton. Small interfering RNA-induced inhibition of myosin
      5a and expression of dominant-negative myosin 5a attenuate insulin-stimulated
      glucose transport and GLUT4 translocation. Furthermore, knockdown of Akt2 or
      expression of dominant-negative Akt (DN-Akt) abolished insulin-stimulated
      phosphorylation of myosin 5a, inhibited myosin 5a binding to actin, and blocked
      insulin-stimulated glucose transport. Taken together, these data indicate that
      myosin 5a is a newly identified direct substrate of Akt2 and, upon insulin
      stimulation, phosphorylated myosin 5a facilitates anterograde movement of GLUT4
      vesicles along actin to the cell surface.

PMID- 17515615
TI  - Constipation and incontinence in childhood: two sides of the same coin?

PMID- 17515616
TI  - Avoiding hypernatraemic dehydration in healthy term infants.

PMID- 17515617
TI  - Towards an effective malaria vaccine.

PMID- 17515618
TI  - Intercountry adoption.

PMID- 17515619
TI  - Spinal extradural haematoma due to haemophilia A.

PMID- 17515620
TI  - A case of familial unilateral tight shoe.

PMID- 17515621
TI  - Extreme thrombocytosis in admissions to paediatric intensive care: no requirement
      for treatment.
AB  - Extreme thrombocytosis (ExtThr; platelet count > or =1000x10(9)/l) is uncommon
      but may have an increased occurrence in critically ill children. The incidence of
      ExtThr for children on the Paediatric Intensive Care Unit at Bristol Royal
      Hospital for Children between January 2001 and December 2004 was calculated, and
      the notes of children identified with ExtThr were reviewed for possible common
      aetiological factors, potential treatment regimes and outcome.

PMID- 17515623
TI  - Dyspraxia or developmental coordination disorder? Unravelling the enigma.
AB  - Dyspraxia is an enigma to many people, both professional and lay alike--what is
      it, how does it relate to developmental coordination disorder and associated
      conditions, how common is it, how is it recognised and diagnosed and how should
      it be managed? This article attempts to unravel this enigma by: dealing with the
      terminology of coordination difficulties from the "clumsy child syndrome" through
      "dyspraxia" to "developmental coordination disorder (DCD)"; briefly examining the
      debate as to whether dyspraxia or DCD should be regarded as a medical or social
      disorder; discussing the differential diagnosis of dyspraxia or DCD; considering
      the assessment of children with dyspraxia or DCD; reviewing the range of current
      treatment approaches in the UK.

PMID- 17515624
TI  - Red fingers syndrome and HIV infection.

PMID- 17515625
TI  - How to diagnose autism.
AB  - Over the past two decades, there has been an explosion of interest in autism and
      autism spectrum disorders. Knowledge and awareness of the condition has grown
      exponentially at all levels among the general public, parents, health
      professionals, the research community and, more recently, at parliamentary level.
      Alongside the increased understanding of these complex and disabling conditions
      is the acknowledgment of a broadening of the diagnostic criteria away from a
      narrow definition of autism to the autism spectrum with less clear diagnostic
      boundaries. Growing evidence of the importance of early diagnosis and
      intervention demands knowledge and skills from all professionals working with
      young children and in particular those involved in recognising early concerns
      about a child's development. This article outlines current clinical and research
      findings in relation to early diagnosis and considers the role of the
      paediatrician in this process. Reference is also made to the National Autism Plan
      for Children.

PMID- 17515627
TI  - Countdown to 2015: will the Millennium Development Goal for child survival be
      met?
AB  - The Millennium Development Goals (MDGs), ratified by most nations in 2000, set
      specific targets for poverty reduction, eradication of hunger, education, gender
      equality, health and environmental sustainability. MDG 4 aims to reduce child
      mortality with a target of reducing under-five mortality rates by two thirds over
      the period 1990-2015. Over the last year, Live Aid, Make Poverty History, the G8
      summits and prominent entertainers have directed unprecedented attention towards
      development and health. Africa particularly has been in the spotlight. Reports
      are published and commitments are made, but is there real progress? Are poor
      people being reached with essential health care? Who will hold leaders to
      account: celebrities, activists or health professionals?

PMID- 17515628
TI  - I've had this problem for ages, perhaps you can help...

PMID- 17515629
TI  - And what do you do?

PMID- 17515630
TI  - Concerns with the linear regression model.

PMID- 17515631
TI  - Hyperchloraemic acidosis in patients given rapid isotonic saline infusions.

PMID- 17515632
TI  - Survey of telephone calls to tertiary paediatric neurology specialist registrars.

PMID- 17515633
TI  - Clinical and laboratory profile of dengue, leptospirosis and malaria in children:
      a study from Mumbai.

PMID- 17515635
TI  - Is it valuable to examine more than one sputum smear per patient for the
      diagnosis of pulmonary tuberculosis?
AB  - The simplest, cheapest, and fastest diagnostic method for tuberculosis (TB) is
      the detection of acid-fast bacilli (AFB) by microscopy. The algorithm advised for
      the diagnosis of TB recommends examination of three consecutive sputum specimens
      from TB suspects for the presence of AFB. In the present study, we evaluated the
      contribution of each specimen to the final detection of TB suspect patients with
      culture-proven disease. The collection and analysis of retrospective data on
      patients with culture-proven pulmonary TB, from June 2002 to August 2006 at Dokuz
      Eylul University Hospital, Turkey, have enabled us to assess the value of
      examining two sputum specimens in diagnosing this disease. AFB were detected from
      one or more sputum specimens with direct microscopy in 42% of the cases. An
      analysis of results of smear examination showed that 97% of AFB were detected
      from the first specimen and only 3% were obtained from the second smear. The
      third specimen did not have any additional diagnostic value for the detection of
      AFB by microscopy. As a conclusion the present study shows that examining two
      sputum smears is sufficient for the early detection of AFB in our laboratory.

PMID- 17515636
TI  - Enteric opportunistic parasites among HIV infected individuals: associated risk
      factors and immune status.
AB  - Data on various etiologic agents causing diarrhea in human immunodeficiency virus
      type-1 (HIV-1) infected individuals are sparse in Delhi, India. The present study
      was undertaken to identify various causative agents, the role of associated risk
      factors and immune status. A case-control study was conducted among 75 HIV-1
      infected individuals, 50 with and 25 without diarrheal infection. Fecal samples
      were screened for coccidian parasites, enteric protozoa, and helminthes by using
      various staining techniques. The CD4+ T-lymphocyte count was estimated. Enteric
      parasites were identified among 62.7% individuals, of which Cryptosporidium
      emerged as the single largest pathogen predominant among 33% of the individuals
      (P < 0.025). Other parasites diagnosed that were significantly associated with
      diarrhea were Giardia lamblia (13.3%), microsporidia (6.7%), and Isospora belli
      (2.7%). Chronic infected diarrheal cases were found to have polyparasitic
      infections. The mean CD4+ cell count was found to be lower among the diarrheal
      cases when compared with the non-diarrheal cases (mean, 141 cells/mm(3) versus
      390 cells/mm(3)). Similarly, among diarrheal individuals, the chronic diarrheal
      cases had a comparatively lower CD4+ cell count than the acute cases (mean, 123
      cells/mm(3) versus 265 cells/mm(3)). Risk factors found significant during
      multivariate analysis were: residence in a slum, exposure to pets and animals,
      use of public toilets, and practice of unsafe homosexual activity. Enteric
      coccidian parasites were identified as significant agents associated with
      diarrhea, especially among those with improper hygiene, multiple infections and a
      lower CD4+ cell count. Thus, this study emphasizes the need for routine screening
      of enteric parasites as well as education about practicing personal hygiene and
      taking timely and appropriate prophylactic measures.

PMID- 17515637
TI  - Genotype and antibiotic susceptibility patterns of Pseudomonas aeruginosa and
      Stenotrophomonas maltophilia isolated from cystic fibrosis patients.
AB  - The purpose of this study was to type the Pseudomonas aeruginosa and
      Stenotrophomonas maltophilia isolates recovered from cystic fibrosis (CF)
      patients by random amplified polymorphic DNA (RAPD)-PCR and to determine the
      antibiotic susceptibility of these strains. P. aeruginosa (n=49), and S.
      maltophilia (n=11) isolates which had been recovered from 16 and 8 patients,
      respectively, during a 1-year period were investigated. Three primers were used
      for RAPD-PCR typing. Antibiotic susceptibility testing of all isolates was
      performed by the disc diffusion method. RAPD-PCR analysis revealed 21 (P.
      aeruginosa) and 9 (S. maltophilia) different genotypes. According to the
      antimicrobial susceptibility results, the P. aeruginosa and S. maltophilia
      strains were cumulated into 24 and 11 groups, respectively. The CF patients were
      colonized or infected with P. aeruginosa strains of single or sometimes multiple
      genotypes which remained stable over several months. Our results also revealed
      that cross-colonization might be possible among the patients who are followed up
      at the same center. Piperacillin-tazobactam for P. aeruginosa and trimethoprim
      sulfamethoxazole for S. maltophilia were found to be the most active antibiotics
      according to our results.

PMID- 17515638
TI  - The risk factors for infections acquired by cerebral hemorrhage and cerebral
      infarct patients in a neurology intensive care unit in Turkey.
AB  - Few studies have investigated the risk factors for nosocomial infections
      developed in neurology intensive care units (ICUs). In this study, the risk
      factors for ICU-acquired infections in patients with cerebral hemorrhage and
      cerebral infarct who were treated for more than 24 h at the Ankara Training and
      Research Hospital were prospectively evaluated over a study period of 14 months.
      Of 171 patients included in the study, 71 (41.5%) were found to have acquired 163
      infections in the ICU unit throughout 1,867 patient days. The rate of infection
      per 100 patients admitted was 95.3, and per 1,000 patient days, 87.3. The most
      common nosocomial infections were urinary tract infection (42.9%), pneumonia
      (27%) and primary bacteremia (19%). Multivariate logistic regression analysis
      revealed age > or = 70 (P < 0.05), the presence of a central venous catheter
      (P=0.004), and parenteral nutrition (P=0.02) as ICU-acquired infection risk
      factors. The presence of infection on admission was identified as a factor
      decreasing the risk of ICU-acquired infection (P < 0.001). The high infection
      rates found in this study may be due to lack of full compliance to infection
      control measures. In conclusion, each type of ICU has its own epidemiological
      findings for nosocomial infections and thus needs to determine the risk factors
      using periodical surveillance studies to guide control measures.

PMID- 17515639
TI  - Tetanus immunization status among women of childbearing age in Turkey.
AB  - In order to assess the effect of the neonatal tetanus elimination program in
      Turkey, tetanus antibody prevalence among women of childbearing age from three
      selected provinces was evaluated in relation to vaccination doses of the single
      type tetanus vaccine. A combined method of in-house enzyme-linked immunosorbent
      assay and particle agglutination test was used to determine tetanus antibody
      titers. Among 205 women aged 20-39 years, the tetanus antibody level was higher
      in women with 1-3 children than those without children. The geometric mean of the
      log antibody titer was increased proportionally with a slope of 0.405 +/- 0.174
      per dose between 0 and 3 doses (P > 0.05). However, the proportion of 20-39-year
      old women with the protective antibody in the provinces ranged from 54.8 to
      86.6%. Diyarbakir had the lowest immunity with a larger number of children in the
      household, and a lower educational level. The results of our serological study
      demonstrated that the neonatal tetanus elimination program in Turkey is
      effectively promoting immunity against tetanus in pregnant women. However, the
      study also revealed that the tetanus immunity among women of childbearing age was
      still insufficient. Intensive implementation of the supplemental immunization
      activities and encouraging vaccinations through neonatal care services will
      improve the situation.

PMID- 17515640
TI  - PCR and serology were effective for identifying Chlamydophila pneumoniae in a
      lower respiratory infection outbreak among military recruits.
AB  - During endemic infections, the sensitivity of diagnostic tests and rapid
      diagnosis of the respiratory tract pathogens is particularly important.
      Utilization of just one diagnostic technique, such as serological tests or
      polymerase chain reaction (PCR)-based detection methods, during outbreaks of
      lower respiratory tract infections (LRI) can result in some of the patients being
      missed. In this study we aimed to investigate the etiology of LRI in military
      recruits in Izmir, Turkey, among whom several pneumonia cases have been reported
      and 47 patients have been hospitalized. Nasopharyngeal swabs were used for PCR
      analysis of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Legionella spp.
      Serum samples were collected in the acute and convalescent phase of infection for
      C. pneumoniae and M. pneumoniae. Thirty-nine patients were diagnosed with C.
      pneumoniae infection by PCR and/or serology. Diagnoses were established by PCR in
      the acute phase of infection in 40.4% of the group. Based on the results of these
      studies, PCR is a useful method for early detection and identification of C.
      pneumoniae-related LRI outbreaks. However, this technique is not sufficient to
      detect all positive cases per se. After effective therapy and introduction of
      appropriate infection control measures, the outbreak ceased without mortality.
      This is the first closed-community C. pneumoniae outbreak report from Turkey.

PMID- 17515641
TI  - Comparison of the tuberculin skin test and the quantiferon test for latent
      Mycobacterium tuberculosis infections in health care workers in Turkey.
AB  - The aim of this study was to compare the efficacy of the tuberculin skin test
      (TST) and the quantiferon test (QFT) for detecting latent tuberculosis infection
      (LTBI) in health care workers (HCWs). Seventy-six participants who were working
      in Duzce University Hospital, where tuberculosis patients were being treated,
      were included in the study. TST was performed according to the Mantoux technique.
      QFT was performed in accordance with the manufacturer's instructions. A positive
      TST result was defined as an induration diameter of > or = 15 mm. TSTs were
      positive in 41 of 76 participants (53.9%) and QFT was positive in 65 of 76
      participants (85.5%). There was a significant difference between the numbers of
      QFT-positive and TST-positive cases (P=0.02). When the induration diameter of TST
      was > or = 20 mm, QFT positivity was 100%. Multivariate analysis revealed that
      there was a significant correlation between the percentage of patients with QFT
      positivity and the induration diameter of TST (P=0.009). QFT thus seems to be
      more effective for LTBI diagnosis than TST. However, large-scale trials including
      quantitative measurement of QFT in subgroups taking into account the division
      where HCWs are employed and the different results of TST might clarify the
      usefulness of QFT in LTBI diagnosis.

PMID- 17515642
TI  - Formalin-treated UV-inactivated SARS coronavirus vaccine retains its
      immunogenicity and promotes Th2-type immune responses.
AB  - The demand for rapid and simple development of a vaccine against a newly emerging
      infectious disease is increasing worldwide. We previously revealed that UV
      inactivated severe acute respiratory syndrome (SARS)-associated coronavirus (SARS
      CoV) virions (UV-V) elicited high levels of humoral immunity and a weak Th0
      response in mice immunized subcutaneously. To ensure the safety of such a whole
      inactivated SARS-CoV vaccine, we additionally treated the UV-V vaccine with
      formalin, resulting in the UV-F-V vaccine. Analysis of the immunogenicity of the
      UV-F-V+alum vaccine in mice revealed that it generated comparable neutralizing
      serum anti-SARS-CoV IgG antibody levels as the UV-V+alum vaccine. Moreover, both
      vaccines induced similar frequencies of anti-SARS-CoV IgG antibody-producing
      cells in bone marrow. Interestingly, the UV-F-V vaccine induced fewer IgG(2a)
      subtype antibodies and higher interleukin-4 production in vaccinated mice than
      did UV-V. Thus, UV-F-V imposes a Th2-type bias on the immune response, unlike UV
      V. We propose here that doubly-inactivated SARS-CoV virions by UV and formalin
      constitute a safe vaccine that may effectively induce neutralizing antibodies in
      humans.

PMID- 17515643
TI  - Performance and quality assurance of genotypic drug-resistance testing for human
      immunodeficiency virus type 1 in Japan.
AB  - Highly active antiretroviral therapy (HAART) can suppress human immunodeficiency
      virus type 1 (HIV-1) replication and plasma HIV-1 to below detectable levels.
      However, HAART becomes ineffective when drug-resistant viruses emerge during
      HAART. Monitoring drug-resistance mutations in viruses is necessary for selecting
      new drugs or therapies effective at inhibiting such HIV-1 variants. Most
      laboratories in Japan perform the tests using in-house protocols. However, the
      quality of these tests has never been assessed. Our study assessing the accuracy
      and reliability of HIV-1 genotypic drug-resistance testing in 15 laboratories in
      Japan revealed that the quality was very high (97.3% accurate). The errors,
      though rare, were caused by human errors, poor electropherograms, and the use of
      inadequate primers. Here, we propose troubleshooting procedures to improve
      testing accuracy and reliability in Japan.

PMID- 17515644
TI  - Plaque formation by Japanese encephalitis virus bound to mosquito C6/36 cells
      after low pH exposure on the cell surface.
AB  - Japanese encephalitis virus (JEV) formed plaques in mosquito C6/36 cell layers
      after adsorption on the cell surface and exposure to pH values lower than 6.2.
      The number of plaques decreased within pH ranges from 7.4 to 6.4, but increased
      within pH ranges from 6.2 to 5.8. Plaque formation was prevented by treatment of
      the virus with a JEV-neutralizing monoclonal antibody, 503, after virus
      adsorption. Plaque formation was not affected by pretreatment with a specific V
      ATPase inhibitor, bafilomycin A1. The results indicate that JEV successfully
      fused with the C6/36 cell membrane under acidic conditions below pH 6.2, which in
      turn led to plaque formation in C6/36 cell layers. These results suggest that
      productive JEV infection occurs at the C6/36 cell surface via the fusion between
      JEV and the cell membrane.

PMID- 17515645
TI  - The medical overcoat - is it a transmitting agent for bacterial pathogens?
AB  - The aim of this study was to isolate, identify and compare the pathogenic
      bacteria prevalent on the overcoats of doctors, residents and students from
      medical and surgical wards, to determine their antimicrobial sensitivity, compare
      them with isolates from pus collected over the same period, and ultimately make
      recommendations. Using standard procedures, bacteria were isolated and identified
      from the hem and pocket mouths of the overcoats of 80 medical personnel, and drug
      sensitivity tests were carried out. Of the samples from the overcoats, 95%
      (n=152) were positive for bacterial isolates like Pseudomonas aeruginosa,
      Klebsiella sp., Escherichia coli, non-fermenting Gram-negative bacteria,
      Staphylococcus aureus, etc. Six swabs showed double isolates. There was a
      significant (P=0.014) association with the category of the participants (30/34
      from doctors, 44/48 from residents and 78/78 from students). The isolates were
      significantly (P < 0.001) more prevalent on overcoats from surgical wards (n=98,
      100%) than on those from medical wards (n=54, 87%). The pathogens from medical
      overcoats and those from pus samples were both multidrug resistant, though they
      were not similar. Hence overcoats may be a transmitting agent for bacterial
      pathogens. Doctors should be aware of the proper usage and frequency of
      laundering of overcoats.

PMID- 17515646
TI  - Antimicrobial resistance among clinical isolates of Pseudomonas aeruginosa from
      patients in a teaching hospital, Riyadh, Saudi Arabia, 2001-2005.
AB  - Antimicrobial resistance to nine anti-pseudomonal agents (azteronam, ceftazidime,
      cefepime, piperacillin/tazobactam, imipenem, meropenem, ciprofloxacin, amikacin
      and gentamicin), the magnitude of multidrug resistance, associated underlying
      conditions, and mortality among patients with Pseudomonas aeruginosa isolates
      from King Khalid University Hospital, Riyadh, Saudi Arabia from 2001 to 2005 were
      determined. The results showed that antimicrobial resistance among P. aeruginosa
      is gradually increasing for most anti-pseudomonal agents, particularly aztreonam,
      ceftazidime, piperacillin/tazobactam and imipenem. There were 19 (3%) and 12 (2%)
      multidrug-resistant (MDR) P. aeruginosa patients in 2004 and 2005, respectively,
      and MDR P. aeruginosa was more commonly found in non-intensive care unit (ICU)
      patients. Most MDR isolates were from surgical and diabetic patients. The
      mortality rate was higher among ICU patients.

PMID- 17515647
TI  - Klebsiella pneumoniae in neonatal sepsis: a 3-year-study in the pediatric
      hospital of Tabriz, Iran.
AB  - Neonatal sepsis is a life-threatening emergency, and any delay in treatment may
      cause death. Because of the importance of the problem in Iran, the aim of this
      retrospective study was to determine the etiological agents of neonatal
      septicemia, and the prevalence and epidemiology of Klebsiella bacteremia in the
      neonatal wards. Two hundred and ten cases of neonatal sepsis occurred during the
      study period. The most common organism was coagulase-negative staphylococci. Gram
      negative organisms were isolated in 66 cases (31.43%), and the most common Gram
      negative organism causing neonatal sepsis was Klebsiella pneumoniae. The
      mortality rate due to Gram-negative bacteria including K. pneumoniae was higher
      than that due to other bacteria. The distribution of the main pathogens is
      different in the Azerbaijan state, northwest of Iran, and K. pneumoniae is
      predominant, but Streptococcus agalactiae plays a relatively minor role in the
      etiology of sepsis during the first month of life.

PMID- 17515648
TI  - Methicillin-resistant Staphylococcus aureus osteomyelitis and septic arthritis in
      neonates: diagnosis and management.
AB  - Acute osteomyelitis (AO) in neonates, although rare, represents a diagnostic and
      therapeutic challenge. A high index of suspicion is necessary to make an early
      diagnosis, and the observation of clinical signs is crucial. The increasing
      prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is an emerging
      problem in pediatrics. In neonates, MRSA infections can cause a wide spectrum of
      diseases including bone and joint infections. We report two cases of AO in full
      term neonates, with no risk factors, due to MRSA.

PMID- 17515649
TI  - A survey of pathogenic genes from diarrhea stool samples obtained in Nara
      prefecture.
AB  - We conducted a survey of diarrhea stool samples in which no virulent agents had
      previously been detected at clinical laboratories. DNA extracted directly and
      purified from the diarrhea stool was tested for bacterial pathogenic genes by
      polymerase chain reaction. The test results for 85 specimens were as follows: one
      sample was positive for lt, ipaH, and eae; two were positive for aggR; and eight
      were positive for astA. Inoculation with the stool specimens led to the isolation
      of a strain of Escherichia coli possessing eae, three strains of E. coli
      possessing astA, and a strain of Klebsiella possessing astA.

PMID- 17515650
TI  - Cytomegalovirus-associated pseudotumor simulating gastric malignancy in acquired
      immunodeficiency syndrome: a case report with review of literature.
AB  - We present a case of cytomegalovirus (CMV)-induced pseudotumor of the gastric
      antrum. Although affliction of the entire gastrointestinal tract with CMV has
      been described, localization to the stomach and especially the gastric antrum is
      rare. Kaposi's sarcoma and non-Hodgkin's lymphoma are recognized causes of bowel
      thickening and obstruction in patients with AIDS, but CMV is an extremely rare
      cause, with only four cases of CMV-induced pseudotumor reported in the English
      literature. As the duration of opportunistic infections and length of survival of
      patients with AIDS increase, CMV pseudotumors are not likely to remain unique.
      This mass lesion should be included in the differential diagnosis of AIDS
      patients, along with Kaposi's sarcoma and non-Hodgkin's lymphoma.

PMID- 17515651
TI  - Simultaneous detection of the genus Brucella by combinatorial PCR.
AB  - We have developed a combinatorial polymerase chain reaction (PCR) procedure to
      identify four major species of the genus Brucella simultaneously. Four pairs of
      primers targeting the genes encoding a cell surface protein (BCSP31) and outer
      membrane proteins (omp2b, omp2a and omp31) were prepared. PCR using these primers
      gave rise to specific patterns of amplification for each Brucella spp. examined
      in this study. B. abortus could be identified when fragments of BCSP31 and
      omp2b/2a were amplified by B. abortus-specific primers. B. melitensis could be
      identified by the amplification of fragments of BCSP31, omp2b/2a and omp31 using
      pair of primers B4/B5, JRF/JPR-ab and omp31. Identification of B. canis could be
      achieved when the amplicons of omp2b/2a were detected by B. canis-specific
      primers, as could the identification of BCSP31 and omp31. If specific
      amplifications occurred using all pairs of primers, the strain was identified as
      B. suis. Combinatorial PCR reported here thus appeared to be an ideal method of
      identifying Brucella spp., the causative pathogen of human brucellosis.

PMID- 17515652
TI  - Development and evaluation of a multiplex PCR for rapid detection and
      differentiation of Mycobacterium tuberculosis complex members from non
      tuberculous mycobacteria.
AB  - Most mycobacterial infections are still caused by Mycobacterium tuberculosis
      complex (MTC) strains; however, infections by non-tuberculous mycobacteria (NTM)
      are increasing, particularly among immunocompromised patients. Conventional
      species-specific identification and proper patient management are delayed due to
      the slow-growing nature of mycobacteria. We have developed a multiplex PCR (mPCR)
      targeting the oxyR-ahpC intergenic region and rpoB gene for direct detection and
      differentiation of clinical isolates as MTC or NTM in primary culture. Two
      amplicons of 473 bp and 235 bp from MTC members and a single amplicon of 136 bp
      from NTM are expected. The mPCR was developed using several mycobacterial species
      and was evaluated by testing extracted DNA from liquid cultures, flagged as
      positive for bacterial growth, of 100 consecutive mycobacterial isolates. The
      results were validated by DNA sequencing of the species-specific 16S-23S internal
      transcribed spacer (ITS) region. The mPCR with template DNA from reference
      Mycobacterium spp. yielded the expected amplicons. When 100 consecutive clinical
      isolates of Mycobacterium spp. were tested, 92 strains yielded MTC member
      specific amplicons, and DNA sequences from 10 randomly selected isolates matched
      completely with the ITS sequence from M. tuberculosis. Eight isolates were
      identified as NTM, and DNA sequencing of the ITS region confirmed the NTM status
      of each of these isolates. The mPCR developed in this study allowed rapid
      detection and differentiation of primary cultures as MTC or NTM, thus helping in
      timely institution of specific therapy.

PMID- 17515653
TI  - Food poisoning caused by mannitol nonfermenting Staphylococcus aureus: case
      report.

PMID- 17515654
TI  - Outbreak of norovirus gastroenteritis involving multiple institutions.

PMID- 17515655
TI  - Dual mutations in the HA1 peptide of amantadine-resistant influenza viruses at
      positions 193 and 225.

PMID- 17515656
TI  - Detection of the rotavirus a genome from the cerebrospinal fluid of a
      gastroenteritis patient: a case report.

PMID- 17515657
TI  - Detection of the tetanus toxin gene by polymerase chain reaction: a case study.

PMID- 17515658
TI  - Outbreak of hepatitis A virus infection caused by food served in a restaurant.

PMID- 17515659
TI  - Epidemics of influenza from winter to summer in the 2005/06 season in Sapporo,
      Japan.

PMID- 17515660
TI  - A food poisoning diarrhea outbreak caused by enteroaggregative Escherichia coli
      serogroup O126:H27 in Shizuoka, Japan.

PMID- 17515661
TI  - A model for the induction of DNA damages by fast neutrons and their evolution
      into cell clonogenic inactivation.
AB  - It has been long stated that cellular inactivation through neutron irradiation is
      mainly caused by energy deposition in DNA molecules from recoiled secondary
      charged particles. Complexities associated with neutrons, such as the generally
      broad energy spectrum and the inherently wide energy spectrum of the induced
      charged particles, not to mention that the dependence of cellular inactivation by
      charged particles on radiation quality is yet to be fully understood, make it
      difficult to check this statement. Recently a molecular model has been proposed
      that improves the quantitative explanation of the dependence of cellular
      inactivation by charged particles on radiation quality. An attempt was made to
      apply this model for analysis of neutron cellular inactivation. As a preliminary
      result it is suggested that neutron cellular inactivation is caused not only by
      secondary charged particles but also by an "atomic deletion" effect, generated by
      a stripped atom recoiling from a DNA molecule. This effect seems to be of
      significant importance, the inactivation cross section of this effect for fission
      neutrons is as much as 15% (aerobic conditions) or 55% (hypoxic) of the total,
      and the severity of one occurrence of atomic deletion by a single neutron is
      estimated as much as 3.1 +/- 1.1 times (aerobic) or 6.8 +/- 1.2 times (hypoxic)
      higher than the severity of one event by a single track of a charged particle
      interacting with DNA.

PMID- 17515662
TI  - [The pathophysiology of food allergy].

PMID- 17515663
TI  - [Characteristics of food allergens].

PMID- 17515664
TI  - [Food-dependent exercise-induced anaphylaxis].
AB  - Food-dependent exercise-induced anaphylaxis (FEIAn) is a rare disease. The
      disease is classified into physical allergy and/or a subtype of food allergy.
      However, the pathophysiology and epidemiology are not well known. In this article
      we presented our studies of the epidemiology of FEIAn, in school students
      (elementary. junior-high, and high school) in Yokohama City and/or Kanagawa
      Prefecture, Japan. Also, we reviewed FEIAn cases in the literatures in Japan as
      well as in foreign countries. Six hundred and seven school nurses responded the
      questionnaire, 30 (Male:Female, 24:6) cases of FEIAn and 44 (M:F, 22:22) with
      exercise-induced anaphylaxis (EIAn) among 353977 students were reported. The
      frequency of FEIAn and EIAn was 0.0085% and 0.012%, respectively. Only one third
      of nurses had knowledge of FEIAn. We performed provocation tests in 11 of the 30
      students with FEIAn and confirmed the diagnosis. We demonstrated transient
      increases in plasma histamine but not serum tryptase levels during the tests. The
      causative foods were mainly wheat and crustaceans in 170 Japanese cases and beans
      and wheat in foreign countries. As for exercise, ball games and running were more
      frequent sports in both groups. The age of first episode of FEIAn was 10 to 20
      years old in most cases. Provocation test often fails to induce symptoms. In
      addition, we do not have the standard method. Now we are establishing the
      protocol. FEIAn and EIAn are relatively rare among school students in Japan.
      There is no evidence to prevent the onset of FEIAn with medicines. Therefore, to
      avoid serious outcomes and unnecessary restriction, we believe it is important to
      be familiar with the diseases for not only physicians, but also school nurses and
      teachers of physical education.

PMID- 17515665
TI  - [Future aspect of Japanese society of allergology].

PMID- 17515666
TI  - [Pathogenesis and treatments of airway mucus hypersecretion].

PMID- 17515667
TI  - [The change of exhaled nitric oxide levels in early response after inhaled
      antigen in antigen-specific provocation test].
AB  - BACKGROUND: Inhaled antigen increases exhaled nitric oxide (eNO) in atopic
      asthmatics. Recent study showed that the increase of eNO levels was observed in
      late response (8-10 hours after inhaled antigen) but not in early response (1.5
      hour after inhaled antigen). But we recognized that in some asthmatics eNO levels
      were increased during early response induced by antigen. METHODS: Atopic stable
      subjects with asthma induced by specific antigen (mite 11, housedust 3) were
      recruited in this study. Through bronchial provocation test with Mite or
      Housedust antigen, eNO levels were examined. As the control group, 7 atopic
      asthmatics who were not induced by specific antigen were recruited. RESULTS: In 7
      subjects, the levels of eNO were increased during early response after inhaled
      antigen, and in other 7 subjects the levels of eNO were decreased. There were
      significant difference in the falling of FEV1 at threshold between the two groups
      (eNO increased group vs eNO decreased group, 22.1+/-0.87 (%) vs. 44.2+/-6.57 (%),
      p=0.016). In 6 subjects in control group, the levels of eNO were decreased.
      CONCLUSION: Inhaled antigen increased the levels of eNO in some asthmatics during
      early response in bronchial provocation test. The level of eNO has possibility of
      predicting the sudden decrease of FEV1 in bronchial provocation test.

PMID- 17515668
TI  - [Characteristics of asthma patients who need repeated hospitalization; frequency
      of use of systemic corticosteroids, emergency and unscheduled hospital visits and
      habitual use of sleeping pills].
AB  - BACKGROUND: This study aimed to analyze the characteristics of frequently
      hospitalized patients. METHODS: The clinical characteristics of 310 cases having
      hospitalization episodes (206 patients) for asthma attack analyzed
      retrospectively based on their clinical records. RESULTS: Nineteen out of the 206
      patients were hospitalized more than just three times during the study period.
      Mean age (once hospitalization group 50.0+/-1.5 y.o., twice- 53.0+/-2.6 y.o., >
      or = 3 times- 56.6+/-2.0 y.o., p=0.02) and the ratio of female (once- 55.2%,
      twice- 61.5%, > or = 3 times- 78.9%, p=0.04) were higher among the groups. The
      frequency of use of systemic corticosteroids (once- 23.6%, twice- 50.0%, > or = 3
      times- 59.8%, p<0.01), emergency and unscheduled hospital visits (once- 0.5+/-0.1
      times/6M, twice- 1.3+/-0.3 times/6M, > or = 3 times- 2.7+/-0.2 times/6M, p<0.01),
      and habitual use of sleeping pills (once- 11.8%, twice- 30.8%, > or = 3 times-
      47.4%, p<0.01) were significantly different among the groups. CONCLUSION: Among
      the patients who need repeated hospitalization, the frequency of use of systemic
      corticosteroids, emergency and unscheduled hospital visits, and habitual use of
      sleeping pills were higher.

PMID- 17515669
TI  - [Metal allergy to implanted orthopedic prosthesis of the knee from which
      suppurative drainage persisted].
AB  - A 63-year-old Japanese woman who had been taking 5 mg of prednisolone per day for
      rheumatic arthritis from the age of 23 years underwent surgery on the right knee,
      during which an orthopedic prosthesis made of an alloy of cobalt (Co) and
      chromium (Cr) was implanted, in November 2000. Two years and 7 months later, a
      painful edema developed over the right knee. Although repeated aspiration of the
      joint yielded a yellow-green fluid, the culture of which was negative, she was
      given antibacterial drugs. The orthopedic prosthesis of her right knee broke in
      November 2003, and she underwent a 2nd operation to replace the Co and Cr alloy
      prosthesis in January 2004. One week after the 2nd operation, redness and
      swelling of her right knee developed, and suppurative drainage continued from the
      pin-hall of the wound. Although repeated bacterial and fungal cultures of pus
      were negative, she was given antibiotics. A 2-day closed patch test with a metal
      allergen from Torii Pharmaceutical Co. Ltd (Tokyo Japan) showed positive
      reactions to only Co and Cr in December 2004. She underwent a 3rd operation to
      remove the Co and Cr alloy prosthesis of her right knee in February 2005, and
      suppuration improved 2 months later. A diagnosis of Co-Cr alloy allergy mimicking
      suppurative arthritis was made. Patch testing is indispensable for patients with
      persistent inflammation after implantation of a prosthesis made of an alloy of Co
      and Cr and for preoperative patients for whom implantation of a prosthesis made
      of metals is planned.

PMID- 17515670
TI  - [Propolis' antimicrobial activity: what's new?].
AB  - Propolis is a hive product that bees manufacture from balsamic resins actively
      secreted by plants on leaf buds and barks. Propolis composition is highly
      variable, depending on the plant species and on the season of collection.
      However, propolis essentially contains resins, balsams, essential oils,
      flavonoids, vitamins, minerals and pollen, albeit at different concentrations.
      Although more than 300 constituents have been identified in propolis samples,
      biological activity is mainly due to few substances, such as flavonoids, terpens,
      caffeic, ferulic and cumaric acids and esters. Propolis is characterized by
      multifactorial activities, but only some of them have been substantiated by
      clinical and experimental evidence. It is widely acknowledged to exert
      antimicrobial activity against a wide range of microorganisms (bacteria, fungi
      and viruses), but also exerts antiinflammatory, anaesthetic, healing,
      vasoprotective, antioxidant, antitumoral, antiulcer and hepatoprotective
      activities. The wide spectrum of activities has led in recent years to the
      development of new technologies to improve propolis properties of the traditional
      hydroalcoholic extract. This paper reviews the antimicrobial properties of
      propolis, focusing on respiratory pathogens. These characteristics make propolis
      a valid option for therapy of upper respiratory tract infections.

PMID- 17515671
TI  - [Early and timely therapy: when to interrupt antibiotic therapy in nosocomial
      acquired pneumonia?].
AB  - Nosocomial pneumonia is the second most frequent nosocomial infection and
      represents the leading cause of death due to hospital acquired infections. In
      recent years, evidence has accumulated that initial inappropriate antibiotic
      treatment is an important and independent mortality risk factor for patients with
      nosocomial pneumonia. On this point, several authors have found that delaying the
      administration of appropriate antibacterial treatment is associated with an
      excess in hospital mortality. In this scenario, various strategies have been
      proposed, such as de-escalation therapy, that attempt to balance the need to
      provide appropriate initial treatment with limiting the emergence of
      antibacterial resistance. Another relevant point is the duration of antibiotic
      therapy: international guidelines suggest that it should be based upon the
      clinical response, with a standard duration of 14-21 days, but several authors
      have shown that a shorter course could lead to the same clinical results, and
      significantly reduce both antimicrobial consumption and the emergence of
      resistant pathogens. The present review deals with the clinical importance of
      early, shorter antibiotic therapy.

PMID- 17515672
TI  - [Clinical and microbiological features of Salmonella gastroenteritis in
      children].
AB  - The aim of our study was to evaluate the role of Salmonella spp in children
      hospitalised for acute gastroenteritis, and to study clinical and microbiological
      features of paediatric salmonellosis in our geographical area. In all, 540
      patients admitted from March to September 2003 with symptoms of acute enteritis
      to the Infectious Diseases department of the "G. Di Cristina" hospital in Palermo
      were enrolled. Stool samples were collected within 48 hours of admission and
      tested for intestinal pathogens (bacterial, viral, parasites). Salmonella spp was
      detected in 18.5% of samples. The median age of infected children was 4.5 years.
      Salmonella enteritidis (49%) and Salmonella typhimurium (37%) were the most
      commonly identified genotypes. S. enteritidis infection was more frequently
      characterized by vomiting (65.3%) and dehydration (61.2%). Bloody diarrhoea was
      more common in S. typhimurium infection (40.5%). All strains were susceptible to
      ceftriaxone, while 40% of strains were resistant to tetracyclines and 37% to
      ampicillin.

PMID- 17515673
TI  - [Role of Dientamoeba fragilis in human bowel infections].
AB  - During 2004, we identified 39 intestinal infections caused by Dientamoeba
      fragilis and 23 caused by Giardia duodenalis, on 1141 home subjects (3.4% and
      2.0% respectively): D. fragilis was observed in 4.5% of O and P (29/644 subjects
      suffering from aspecific bowel disorders) and in 2.0% of diarrhoeas (10/497); G.
      duodenalis was observed in 3.1% (20/644) and in 0.6% (3/497) of cases
      respectively. No other pathogenic parasites were identified (only 1 case of
      enterobiasis in an asymptomatic child). Commensal protozoa were observed, among O
      and P, in 4.3% of cases (28/644). The non-pathogenic B. hominis, often associated
      with other protozoa, was observed in 4.1% of all 1141 cases. D. fragilis is
      undoubtedly more frequent in adults (36/39 cases, 92.3%) than in children (3/39,
      7.7%), and is prevalent among females (24/39, 61.5%) in respect of males (15/39,
      38.5%). G. duodenalis is more prevalent among adults (16/23, 69.5%) than children
      (7/23, 30.5%), but is more frequent among males (13/23, 56.5%) than females
      (10/23, 43.5%). Clinical correlations of dientamoebiasis and giardiasis are
      reported, seasonal and epidemiological features of these protozooses are
      outlined, and the authors emphasize the importance and need of Giemsa stain,
      among O and P and acute or prolonged diarrhoeas, on the basis of previous good
      direct microscopic observations of faecal specimens, for correct and complete
      diagnosis of intestinal infections.

PMID- 17515674
TI  - [Tuberculosis meningitis in adults: 5 cases].
AB  - Tuberculosis still represents a problem of public health of worldwide importance.
      Tuberculosis meningitis is a rare yet serious infectious disease. The diagnosis
      is mainly clinical and should be considered in a specific epidemiological
      context. Culture of Mycobacterium tuberculosis from cerebrospinal fluid is
      required for definitive diagnosis but it cannot always be obtained. In this study
      we report five cases of tuberculosis meningitis admitted to our Department of
      Infectious and Tropical Diseases over the last six years, highlighting the main
      aspects that steered us towards diagnosis and the difficulties we encountered.

PMID- 17515675
TI  - [Rapid differential diagnosis of Orthopoxviruses and Herpesviruses based upon
      multiplex real-time PCR].
AB  - OBJECTIVE: Variola virus, belonging to Orthopoxviridae family, is one of the most
      dangerous human pathogens that could be used as biological weapon. We have
      developed a new rapid assay, based upon Real-time PCR and melting temperatures
      analysis of amplicons, for the contemporary detection of Orthopoxvirus, VZV and
      HSV1-2, that are the most important infectious agents to be considered for
      differential diagnosis. METHODS: The target for detection of orthopoxvirus DNA
      has been a region of the crmB gene which is common to Variola virus and to other
      old world orthopoxviruses pathogenic for humans. The targets for VZV and HSV1-2
      have been ORF 29 and DNA polymerase, respectively. Suitability of the amplified
      fragments to RFLP or sequencing analysis, to recognize the involved viral
      species, has been also tested. RESULT: The selected primers have showed high
      sensitivity, specificity and compatibility with common amplification conditions.
      A mean melting temperature difference of 8.7 degree C was observed between the
      amplicons from the two virus types. Further identification of individual
      pathogens was made using RFLP analysis. CONCLUSION: The PCR-based protocol set up
      in this study for presumptive differential diagnosis of variola and herpesviral
      infections is rapid and specific and it can be used also to detect other
      orthopoxviral infections, like monkeypox.

PMID- 17515676
TI  - Successful treatment of Corynebacterium urealyticum encrusted cystitis: a case
      report and literature review.
AB  - Encrusted cystitis is a very rare chronic inflammatory disease of the bladder
      characterized by precipitation and incrustation of phosphate and ammonium
      magnesium salts on the vescical mucosa, caused by urinary infection due to
      urolithic microorganisms. Corynebacterium urealyticum or Corynebacterium group
      D2, a multiple antibiotic-resistant urea-splitting bacterium, is the most
      frequently incriminated aetiology. We report a case of a 57-year-old man affected
      by systemic erythematosus lupus with a long history of dysuria and suprapubic
      pain who underwent percutaneous nephrostomy drainage with urethral stenting for
      lupoid obstructive uropathy. Before the diagnosis of encrusted cystitis by
      Corynebacterium urealyticum was established, the patient underwent five
      cystoscopies to remove the plaques and multiple unsuccessful antibiotic treatment
      courses. Eventually the infection was definitively cured after a two-week course
      with intramuscular teicoplanin.

PMID- 17515677
TI  - [Nephrotic syndrome and Gram-negative sepsis in a patient with strongyloidiasis:
      a case report].
AB  - Strongyloidiasis is caused by a small intestinal nematode with a complex life
      cycle. In Italy the infection is endemic in rural areas of the Po Valley. The
      clinical syndrome of S. stercoralis encompasses a broad spectrum of symptoms and
      signs and, in the immunocompromised host, larvae can migrate to different organs
      and tissues. Also immune response seems to play a role in the pathogenesis of the
      disease. We report a case of strongyloidiasis complicated by Gram-negative sepsis
      and nephrotic syndrome in an immigrant from South America with a normal immune
      response. Whereas sepsis cleared up quickly, parasitic clearance was obtained
      only after treatment with ivermectin and nephrotic syndrome was still present
      three months after the end of treatment.

PMID- 17515678
TI  - [Typhoid fever and acute pancreatitis: two cases].
AB  - Acute pancreatitis is a pancreatic inflammation that recognises Salmonella typhi
      among its aetiological agents. In this article the authors describe two cases of
      acute pancreatitis secondary to typhoid fever, evolving towards complete
      recovery. These two cases, besides confirming that Salmonella typhi can be
      responsible for acute pancreatitis, remind us that during typhoid fever, amylase
      enzyme test should be always assessed. Moreover, salmonella infection must also
      be considered in cases of non-alcoholic or non-lithiasic pancreatitis.

PMID- 17515679
TI  - [Smallpox in Ferrara in the nineteenth century].
AB  - The aim of this work was to analyse the mortality for smallpox and the methods
      used during the nineteenth-century to control epidemics. Most of the historical
      material was found in the Historical Archives of the Ferrara City Council. Over
      the whole period in question, there were 710 deaths in Ferrara (366 males and 344
      females). The highest number was found in the years 1816, 1829, 1834, 1842, 1849,
      1871 and 1891. Data analysis shows that most deaths occurred during the first
      half of the century. Subsequently, the phenomenon declined to almost zero. Males
      were more affected and nearly 70% of the deaths occurred under 5 years of age,
      50%of which during the first year of life. At that time, the "guidelines" adopted
      were analogous to those currently followed when a new vaccination programme is
      started. The inspiring principles were the active and free supply of vaccine,
      universal vaccination, the informed consent of the population, the involvement of
      educators and also monetary rewards to the most industrious doctors in the
      practice of vaccination. In Ferrara vaccination began in 1801, but was only
      consistently implemented in 1812. By the end of the 19th century the number of
      persons vaccinated had increased from 3% to 7%. Vaccination initiatives assumed
      great importance among the population of Ferrara, in spite of initial resistance
      and suspicion of a practice which most people found incomprehensible.

PMID- 17515680
TI  - Treatment innovation in rehabilitation of cognitive and motor deficits after
      stroke and brain injury: physiological adjunctive treatments.

PMID- 17515681
TI  - Pharmacological, surgical, and neurovascular interventions to augment acute
      aphasia recovery.
AB  - Aphasia recovery has often been attributed to a combination of "spontaneous
      recovery" and rehabilitation. However, a variety of new pharmacological,
      surgical, and interventional neuroradiology procedures have been developed that
      can complement rehabilitation in the first days to weeks after stroke by
      restoring blood flow to dysfunctional but salvageable brain tissue. This paper
      will review the medical and surgical interventions to improve regional cerebral
      blood flow that recently have been shown to (1) augment aphasia recovery by
      improving tissue function, and (2) prevent expansion of the stroke that would
      otherwise impede recovery. Success with such treatments facilitates aphasia
      rehabilitation by improving the baseline language performance that must be
      improved further with language therapy.

PMID- 17515682
TI  - Vitamin D status of patients admitted to a hospital rehabilitation unit:
      relationship to function and progress.
AB  - OBJECTIVE: The primary objective was to determine the association between vitamin
      D status, baseline function, and short-term inpatient rehabilitation progress.
      DESIGN: This was a prospective convenience sampling of 100 patients in a tertiary
      general hospital rehabilitation unit (RU). The cohort comprised men and women of
      mixed race with a variety of diagnoses (mean age 70 yrs). Patient histories and
      demographic information were obtained by patient interview and chart review.
      Serum 25-hydroxyvitamin D (25OHD) (nmol/L) was measured on or after the day of
      admission. The Functional Independence Measurement (FIM) instrument, a validated
      survey tool, was used to measure function at admission and discharge. RESULTS:
      Eleven percent of the patients were overtly vitamin D deficient, with serum 25OHD
      concentrations <20 nmol/L. Ninety-four percent of the patients had serum 25OHD
      concentrations below the recommended minimum optimal concentration of 80 nmol/L.
      Using the Spearman rank correlation test, low serum 25OHD was weakly but
      significantly associated with low total FIM scores: r = 0.25 (P < 0.012) and r =
      0.23 (P < 0.021) for admission and discharge total FIM score, respectively.
      Patients with serum 25OHD concentrations greater than the median value of 41.3
      nmol/L had significantly higher FIM efficiency scores (discharge total FIM score 
      admission total FIM score/length of stay [LOS]) than the subgroup of patients
      below the median (2.0 +/- 1.1 vs. 1.6 +/- 0.9, respectively; P < or = 0.026).
      Serum 25OHD was not significantly correlated with FIM efficiency or the
      unadjusted change in total FIM score (discharge total FIM score - admission total
      FIM score), but it was significantly correlated with LOS (the lower the serum
      25OHD concentration, the longer the LOS, and vice versa; r = -0.235, P < 0.018).
      Thus, the difference in FIM efficiency between patients with serum 25OHD above
      and below the median was the result of the significant inverse correlation
      between serum 25OHD and LOS; as a group, patients with serum 25OHD above the
      median had a 19% shorter LOS than the group with serum 25OHD below the median
      value (11.4 +/- 4.9 vs. 14.1 +/- 5.6 days, respectively; P = 0.005). CONCLUSIONS:
      Most patients in a hospital RU had a suboptimal serum 25OHD concentration,
      reflecting what has previously been observed in hospitalized patients in general
      and also the population at large. Although no specific physical deficits or
      attributes could be directly attributed to low serum 25OHD, the baseline
      functional status of RU patients, LOS, and progress attributable to inpatient
      rehabilitation (FIM efficiency) were favorably affected by higher serum 25OHD
      concentrations.

PMID- 17515683
TI  - Inconsistent knee varus moment reduction caused by a lateral wedge in knee
      osteoarthritis.
AB  - OBJECTIVE: To determine--with the assistance of a larger sample size--whether the
      inconsistency of reducing the knee-joint varus moment with a lateral wedge in
      patients with medial compartment knee osteoarthritis (OA) persists and if so,
      what underlying mechanisms may explain it. DESIGN: Crossover design whereby 51
      patients with bilateral isolated medial compartment knee OA and 19 age-matched
      healthy controls walked with two different wedge conditions: a 0-degree control
      wedge and a 6-degree lateral wedge. We conducted three-dimensional motion
      analysis, hip-knee-ankle (HKA) angle measurement, and radiologic assessment with
      Kellgren-Lawrence grade. We investigated frontal plane angles and moments at the
      knee and subtalar joints, ground reaction forces, and center of pressure (CoP).
      Moments were derived using a three-dimensional inverse dynamics model of the
      lower extremity. RESULTS: Nine patients (17.6%) had an increased knee-joint varus
      moment with the 6-degree lateral wedge via the medially shifted location of the
      CoP. These patients did not differ from the remaining patients in HKA angle and
      radiologic assessment. CONCLUSION: In approximately 18% of patients with
      bilateral medial compartment knee OA, the 6-degree lateral wedge seems to fail to
      reduce the knee-joint varus moment. The indication and limitations of lateral
      wedge should be confirmed by a randomized controlled study.

PMID- 17515684
TI  - Effect of short-term hospitalization on functional capacity in patients not
      restricted to bed.
AB  - OBJECTIVE: It has been suggested that long-term bed rest induces significant
      changes in most organ systems. However, few studies have focused on the effect of
      short-term hospitalization. The aim of the present study was to evaluate the
      effect of short-term hospitalization on functional capacity in patients not
      restricted to bed. DESIGN: We evaluated 78 patients before and after a 5-day
      hospitalization. RESULTS: The following differences were observed between pre-
      and post-hospitalization outcomes: upper-limb muscle strength, 30 +/- 7.9 vs.
      28.4 +/- 7.7 kg (P < 0.001); maximal inspiratory pressure, -83.3 +/- 25.0 vs. 
      70.9 +/- 23.1 cm H2O (P < 0.001); distance covered in the 6-min walk test, 476.2
      +/- 93.1 vs. 437.7 +/- 89.5 m (P < 0.001); forced vital capacity, 3.25 +/- 0.95
      vs. 2.95 +/- 0.93 liters (P < 0.001); spinal mobility, 4.3 +/- 0.9 vs. 3.7 +/-
      0.9 cm (P < 0.001); and trunk mobility, 8.1 +/- 1.9 vs. 7.3 +/- 1.6 cm (P <
      0.001). None of the anthropometric or clinical data collected at admission were
      predictive of these losses. CONCLUSION: Our results suggest that short-term
      hospitalization reduces functional capacity, even in patients who are not
      restricted to bed, regardless of age or initial functional status.

PMID- 17515685
TI  - Measurement properties of the L test for gait in hospitalized elderly.
AB  - OBJECTIVE: Evaluate the reliability, validity, and predictive value of the L
      test, a performance-based walk test, among older inpatients. DESIGN: Cross
      sectional study involving a consecutive sample of 50 older adults (mean age 84 +/
      5 yrs) admitted to the geriatric unit of a tertiary care hospital. Application
      of the L test twice and single application of the timed "up and go" test (TUG),
      and the Frailty and Injuries Cooperative Studies of Intervention Techniques
      (FICSIT-4) balance scale, were conducted. RESULTS: Interrater and intrarater
      reliability (two-way ANOVA intraclass correlation coefficients [ICC]) of the L
      test was 1.00 (95% confidence interval, CI, 0.99-1.00) and 0.97, respectively
      (CI, 0.95-0.98). Hypothesized associations with the TUG and FICSIT-4 were
      observed (Pearson product-moment correlation, r = 0.96 and r = -0.45,
      respectively; P < 0.01) with regard to magnitude and direction of the
      relationship. L test times demonstrated a small but statistically significant
      independent risk factor for discharge destination after hospitalization (odds
      ratio = 1.05; CI, 1.01-1.09) after adjustment for age, sex, and cognitive status.
      CONCLUSIONS: The L test provides reliable, valid data when assessing basic
      walking skills among older adults in a hospital environment. The L test is
      potentially an important clinical and research tool to assess the mobility
      function of older inpatients as they transition back to the community.

PMID- 17515686
TI  - Reliability of a portable gas analyzer during a 5-min walk test.
AB  - OBJECTIVE: To determine the reliability of a gas analyzer while assessing oxygen
      consumption (.VO2) during a 5-min walking test. DESIGN: Forty healthy
      participants were connected to the KB1-C and walked for 5 mins on a 5-m walkway.
      Total .VO2 or energy expenditure (EE) was obtained by averaging the samples for
      each minute for 5 mins. of walking. Walk distance (D), gait speed (S), and gait
      energy cost (C) were also evaluated. RESULTS: The ICC(2,1) for EE, D, S, and C
      were 0.88, 0.92, 0.92, and 0.67, respectively. The coefficient of variation
      across trials for each variable was 7.4, 3.6, 3.2, and 9%, respectively.
      CONCLUSION: All but C generated high coefficients of reliability. All variables
      demonstrated acceptable test-retest variability. There was low variability
      between participants for C.

PMID- 17515687
TI  - Comparison of recovery strategies on muscle performance after fatiguing exercise.
AB  - OBJECTIVE: The objective of this study was to assess the influence of different
      relaxation modes: stretching (ST), active recovery (AR), and passive recovery
      (PR) on muscle relaxation after dynamic exercise of the quadriceps femoris.
      DESIGN: Ten healthy male volunteers between 24 and 38 yrs of age participated in
      this study. After the warm-up, subjects performed three sets of dynamic leg
      extension and flexion (at an angle of 20-110 degrees) at 50% of previously
      determined maximal voluntary contraction (MVC), with 30 secs. of rest between
      sets. Immediately after completing the leg exercise, one of the relaxation
      methods was applied, in a randomized order (AR, PR, ST). Then, subjects performed
      isometric knee extension at 50% of MVC to the point of fatigue, and surface
      electromyogram (EMG) of the vastus lateralis muscle was measured. RESULTS: After
      AR, the mean MVC was significantly (P < 0.05) higher than after PR and ST.
      Moreover, there was no difference in MVC between AR and baseline (P > 0.05).
      Total time of the effort during EMG measurement was significantly lower for all
      three recovery modes than at baseline. During the effort after both PR and ST,
      there was no significant increase in motor unit activation, but a significant
      increase was noted after AR (P < 0.05). There was no difference in frequency
      between any of the recovery modes and baseline (P > 0.05). CONCLUSION: The
      results of this study suggest that the most appropriate and effective recovery
      mode after dynamic muscle fatigue involves light, active exercises, such as
      cycling with minimal resistance.

PMID- 17515688
TI  - Adapting multiple-family group treatment for brain and spinal cord injury
      intervention development and preliminary outcomes.
AB  - OBJECTIVE: There is a need for interventions that assist in managing the multiple
      adjustments of persons with spinal cord and brain injuries and their families.
      The purpose of the present field-initiated development project was to adapt a
      family psychoeducation model, multiple-family group treatment (MFGT), for persons
      with brain and spinal cord injury and their families. DESIGN: The experiences of
      survivors and caregivers in MFGT were evaluated using quantitative and
      qualitative methods. Twenty-seven survivors and 28 caregivers participated in
      MFGT for 12-18 mos. Reliable and valid quantitative measures were used to assess
      a variety of target outcomes. Additionally, semistructured interviews and focus
      groups were conducted with participants. RESULTS: Survivors reported a decrease
      in depressive symptoms and anger expression toward others as well as an increase
      in life satisfaction. Caregivers reported a significant reduction in burden. The
      themes derived from the qualitative analysis addressed the normalization of the
      caregiving experience, importance of socialization, improvement in a variety of
      coping skills, and education about the injuries. CONCLUSIONS: The findings
      support the adaptation of MFGT for brain and spinal cord injuries.

PMID- 17515689
TI  - Musculoskeletal education in physical medicine and rehabilitation residency
      programs: graduating resident perspective.
AB  - OBJECTIVES: To characterize graduating physical medicine and rehabilitation
      (PM&R) residents physicians' perceptions of their current musculoskeletal (MSK)
      training, to identify barriers perceived by resident physicians to improving MSK
      education experiences, and to compare the views of resident physicians with those
      of PM&R residency program directors. DESIGN: Fourth-year PM&R residents
      graduating in 2004 whose program directors attended the 2004 Association of
      Academic Physiatrists annual meeting were asked to complete an MSK education
      survey developed by the authors. Data were compared with a previous MSK education
      survey that had been completed by PM&R residency program directors. RESULTS:
      Ninety-three of 156 (61%) fourth-year PM&R residents responded after multiple
      contacts. According to residents, the most frequently used MSK education formats
      during residency were MSK lecture series, MSK journal clubs, and MSK workshops.
      Potential barriers to improved MSK education during residency included staff,
      money, and time. If given unlimited resources, most residents would greatly
      increase the use of visiting lecturers, MSK workshops, and MSK lecture series.
      CONCLUSION: Graduating PM&R residents as well as residency program directors
      indicated a strong interest in expanding resident MSK education through the use
      of visiting lecturers. Differences were noted with respect to the use of hands-on
      learning (i.e., MSK workshops [residents]) vs. passive learning (i.e., CD
      ROMS/DVDs and videos [program directors]). Both groups described how limited
      resources including staff, money, and time are barriers to resident MSK
      education.

PMID- 17515690
TI  - Effect of dynamic weight bearing on neuromuscular activation after spinal cord
      injury.
AB  - OBJECTIVE: To determine whether individuals who have a spinal cord injury have
      neuromuscular and physiologic responses to a personalized exercise program during
      dynamic weight bearing (DWB). DESIGN: Four subjects with spinal cord injuries
      (T6, T5-6, C2-5, and C5) completed a 12-wk exercise program that included DWB.
      Surface electromyography (EMG) was recorded from the right gastrocnemius, biceps
      femoris, rectus femoris, rectus abdominus, and external oblique. Heart rate (HR)
      and blood pressure (BP) were recorded throughout training. Descriptive statistics
      were used to analyze the data. RESULTS: The results of this study indicate that
      the subjects actively responded to exercise during DWB, as measured by EMG, HR,
      and BP. CONCLUSIONS: The results suggest that exercise during DWB can induce
      physiologic and neuromuscular responses in individuals who have a spinal cord
      injury, and that exercise during DWB may serve as a preparatory program for more
      advanced rehabilitation.

PMID- 17515691
TI  - Iatrogenic axillary neuropathy after intramuscular injection of the deltoid
      muscle.
AB  - A previously healthy 26-yr-old male presented for an electrodiagnostic evaluation
      with complaints of significant right deltoid muscle atrophy and shoulder
      abduction weakness after receiving an intramuscular (IM) deltoid injection of an
      antiemetic 4 wk earlier. Electrodiagnostic evaluation confirmed an acute axillary
      neuropathy. We hypothesize that direct mechanical trauma to the anterior branch
      of the axillary nerve resulted in axillary mononeuropathy with axonal loss,
      although chemically induced nerve injury cannot be excluded. Injections in and
      about the shoulder complex are performed routinely for the purposes of
      vaccination, IM medication administration, deltoid trigger-point injections, and
      intra-articular and bursal steroid injections. Although such injections are
      considered routine office procedures, there is increased risk of neurovascular
      injury if they are performed incorrectly. The purpose of this brief report is to
      make practitioners aware of the potential for axillary neuropathy with such
      procedures, to review the salient anatomy, and to propose a potential guideline
      for clinical practice to minimize iatrogenic axillary neuropathy.

PMID- 17515692
TI  - A very bad prognosis for awakening from coma.

PMID- 17515693
TI  - Guilt by association.

PMID- 17515694
TI  - Biologic generics.

PMID- 17515695
TI  - Mandatory comparator trials for therapeutically similar drugs: an assessment of
      the facts.

PMID- 17515696
TI  - The pharmacokinetics of cinacalcet are unaffected following consumption of high-
      and low-fat meals.
AB  - Cinacalcet HCl reduces iPTH, serum calcium, serum phosphorus, and the calcium
      phosphorus product in patients with chronic kidney disease and secondary
      hyperparathyroidism who are receiving dialysis, and reduces elevated serum
      calcium associated with primary hyperparathyroidism and parathyroid carcinoma.
      Cinacalcet is administered orally, and thus concomitant administration with food
      may affect its bioavailability. The objective of this study was to examine the
      effect of fat and caloric intake on cinacalcet exposure. This phase 1,
      randomized, open-label, single-dose, 3-period, 3-treatment, 6-sequence crossover
      study enrolled 30 healthy subjects (19 men, 11 women) to receive a single oral
      dose of cinacalcet HCl (Sensipar/Mimpara; Amgen Inc. Thousand Oaks, CA) (90 mg)
      on 3 separate occasions: following a high-fat, high-caloric meal, a low-fat, low
      caloric meal, and a 10-hour fast. Blood samples were obtained predose and up to
      72 hours postdose for pharmacokinetic (AUCinfinity, Cmax) and safety evaluations.
      Twenty-nine subjects completed all the 3 treatment conditions. The mean (90%
      confidence intervals) AUCinfinity following high- and low-fat meals was increased
      by 68 (48 to 89)% and 50 (33 to 70)%, respectively, relative to fasting. The
      difference in mean AUCinfinity between high- and low-fat meals was small [12 (9.9
      26)%]. The mean tmax of cinacalcet was prolonged in fasting subjects (6 h) in
      relation to high-fat (4 h) and low-fat (3.5 h) fed subjects. The mean t1/2beta
      was similar between treatment conditions. Adverse events (AE) were observed at a
      similar frequency across the treatment conditions [high fat (34%), low fat (23%),
      and fasting (31%)]; the type of AE did not differ among the treatment conditions.
      The most common treatment-related AEs were headache 6/30 (20%), nausea 5/30
      (17%), and dyspepsia 4/30 (13%) subjects. Administration of cinacalcet with
      either high- or low-fat meals results in significant increases in exposure,
      relative to administration under fasting conditions. However, the small
      differences observed in exposure following the ingestion of the different types
      of meals suggest that although food has a significant effect, the type of food
      does not. The observed effect supports the labeling statement that cinacalcet be
      taken with food, or shortly after a meal.

PMID- 17515697
TI  - Persistence with once-daily versus twice-daily bupropion for the treatment of
      depression in a large managed-care population.
AB  - In this study, the impact of dosing frequency [once daily with bupropion extended
      release (XL) versus twice daily with bupropion sustained-release (SR)] on
      medication persistence was assessed over a 9-month period in a large cohort of
      patients with depression in a managed-care setting. Administrative claims data
      from the Integrated Health Care Information Services National Managed Care
      Benchmark database were analyzed for patients 18 to 64 years old with a
      documented diagnosis of depression who began treatment with bupropion XL or SR
      between September 2003 and February 2004. Persistence of use was higher with once
      daily bupropion XL (n = 1074) than with twice-daily bupropion SR (n = 1917)
      across measures assessed by univariate tests of proportions. The mean (+/-SD)
      number of days between the first and last prescription claims was longer with
      bupropion XL (128.37 +/- 103.46 days) than with bupropion SR (82.31 +/- 96.86
      days) (P < 0.0001). The bupropion XL cohort had higher persistency of use than
      the bupropion SR cohort (mean +/- SD = 0.47 +/- 0.38 versus 0.30 +/- 0.36) (P <
      0.0001) and a higher medication possession ratio (mean +/- SD = 0.50 +/- 0.33
      versus 0.36 +/- 0.31) (P < 0.0001). Medication persistency >0.7 and a medication
      possession ratio >0.7 were almost twice as likely in the bupropion XL cohort
      (38.5% and 32.0%, respectively) than in the bupropion SR cohort (21.5% and 17.0%,
      respectively). Results of multivariate analyses adjusted for age, gender, and
      index date support the univariate analyses. Because better persistence and
      adherence may be associated with less likelihood of relapse and lower depression
      associated health care utilization and economic burden, health care providers
      should consider the potential benefits of initiating treatment with bupropion XL
      for bupropion candidates and for switching bupropion SR recipients to treatment
      with bupropion XL.

PMID- 17515698
TI  - The role of cyclooxygenase in the feline pulmonary vascular bed.
AB  - OBJECTIVE: There are extensive data on roles of cyclooxygenase 1 (COX 1) and
      cyclooxygenase 2 (COX 2) enzymes in temperature, coagulation, and inflammatory
      modulation. There is little known of the function of these enzymes in regulating
      tone in pulmonary vasculature. The purpose of this investigation was to elucidate
      the roles of COX 1 and 2 enzymes in the feline pulmonary vascular bed. DESIGN:
      Prospective vehicle controlled study. SETTING: University research laboratory.
      SUBJECTS: Intact chest preparation; adult mongrel cats. INTERVENTIONS: The
      effects of intravascular administration of U46619, angiotensin II, prostaglandin
      E1 (PGE1), arachidonic acid, and norepinephrine, were analyzed before and after
      intravascular administration of selective COX enzyme inhibitors. MEASUREMENTS AND
      MAIN RESULTS: Because lobar arterial flow is constant in these experiments,
      changes in lobar pressure represent changes in pulmonary arterial resistance.
      Under constant flow conditions, lobar arterial and systemic pressures were
      continuously monitored, electronically averaged, and recorded. In the isolated
      left lower lobe of the feline lung bed, U46619, angiotensin II, arachidonic acid,
      and norepinephrine induced a dose-dependent vasoconstrictor response. PGE1
      induced a dose-dependent vasodepressor response. After administration of the COX
      1 inhibitor SC 560, the arachidonic acid-induced vasopressor responses were
      significantly attenuated while U46619, angiotensin II, and norepinephrine-induced
      vasopressor, and PGE1-induced vasodepressor responses were not significantly
      altered. After administration of the COX 2 inhibitor nimesulide, both the PGE 1
      vasodepressor responses and arachidonic acid-induced vasopressor responses were
      significantly decreased while the U46619, angiotensin II, and norepinephrine
      induced vasopressor responses were not significantly attenuated. CONCLUSIONS: The
      results of the study indicate that PGE1 has potent vasodepressor effects in the
      feline lung bed and this response is mediated by COX 2 pathways. The data also
      suggest that arachidonic acid has potent vasopressor activity in the feline
      pulmonary vascular bed and this response is mediated by both COX 1 and COX 2
      sensitive pathways.

PMID- 17515699
TI  - A 5-year survey of nitric oxide use in a pediatric intensive care unit.
AB  - The authors retrospectively reviewed their experience with nitric oxide (NO) in a
      pediatric ICU. Given its cost ($3000/d), ongoing evaluations are required to
      ensure its effective use and avoid inappropriate applications. NO use included 4
      categories: (1) hypoxemic respiratory failure, (2) pulmonary hypertension
      following surgery for congenital heart disease (CHD), (3) intraoperatively for
      surgical procedures such BT shunt placement or 1-lung ventilation, and (4) during
      ECMO. In the 19 patients with respiratory failure, NO resulted in an increase in
      oxygenation in 15 of 19 patients (Pao2/Fio2 ratio increased from 83 +/- 60 mm Hg
      to 188 +/- 105 mm Hg, P = 0.0007). In 4 patients, NO did not improve oxygenation.
      The 15 patients that responded to NO survived, whereas the 4 patients who did not
      respond died (P = 0.0003). NO was used to treat pulmonary hypertension in 19
      patients following cardiopulmonary bypass (CPB) and surgery for CHD. In 13 of 19
      patients, a high pulmonary artery (PA) pressure was documented by direct
      measurement with a needle inserted into the PA while the chest was open (n = 9)
      or a postoperative transthoracic PA catheter (n = 4). NO resulted in a decrease
      in the PA pressure in 9 of 13 patients (37 +/- 5 mm Hg to 21 +/- 3 mm Hg, P <
      0.0001). In the one patient in whom NO did not lower intraoperative PA pressure,
      it was not possible to wean from CPB. For the 10 patients in whom NO was started
      in the PICU, 4 had PA catheters in place and documented elevated PA pressure. NO
      resulted in a significant decrease in the PA pressure in only 1 of these 4
      patients. The survival of responders was 9 of 9 versus 1 of 4 for nonresponders
      (P = 0.014). No significant adverse effects requiring therapy other than
      decreasing the inhaled NO concentration were noted. Potential interventions and
      practices to limit the unwarranted use of this costly agent are discussed.

PMID- 17515700
TI  - Impact of kinetic beds on the incidence of atelectasis in mechanically ventilated
      patients.
AB  - We investigated the impact of kinetic beds on the incidence of atelectasis in
      mechanically ventilated patients in an intensive care unit (ICU). All
      bronchoscopies performed for atelectasis on mechanically ventilated patients
      between July 2000 and June 2001 and between July 2002 and June 2003 were
      reviewed. On July 26, 2001, 50 kinetic beds, 20 continuous lateral rotation
      therapy modules, and 20 percussion and vibration modules were introduced to our
      institution. Of the 3399 ICU admissions between July 2000 and June 2001, 71
      patients developed atelectasis while being mechanically ventilated. Of the 3065
      ICU admissions between July 2002 and June 2003, 83 patients developed atelectasis
      while being mechanically ventilated. Of these, 48 (58%) patients had left-sided
      atelectasis, 30 (36%) had right-sided atelectasis, and 5 (6%) had bilateral
      atelectasis. There was no decrease in the incidence of atelectasis in
      mechanically ventilated patients at our institution after the introduction of
      kinetic beds and vibration, percussion, and rotation modules despite their
      widespread availability.

PMID- 17515701
TI  - Inadequate pyridoxine stock and its effect on patient outcome.

PMID- 17515702
TI  - Serum glucose changes during insulin therapy in pediatric patients with diabetic
      ketoacidosis.
AB  - There are limited data on which to base insulin dosing schemes for diabetic
      ketoacidosis (DKA). The goal of therapy is to avoid excessive decreases in serum
      glucose (greater than 100 mg/dL/h) because of the risks of rapid changes in serum
      osmolarity and the potential risk of cerebral edema. We retrospectively reviewed
      the therapy of DKA in pediatric patients admitted to our Pediatric Intensive Care
      Unit over the past 10 years. There were 35 patients who received IV bolus insulin
      therapy (0.08 to 1.6 units/kg, 0.24 +/- 0.27 units/kg). The serum-glucose
      decrease was less than or equal to 100 mg/dL in 10 patients, 101 to 200 mg/dL in
      13 patients, 201 to 300 mg/dL in 8 patients, 301 to 400 mg/dL in 2 patients, and
      more than 500 mg/dL in 2 patients. In patients who received 0.05 to 0.1 units/kg
      of insulin as a bolus dose, the decrease in serum glucose was greater than 100
      mg/dL in 5 of 11 patients. An insulin infusion was administered to 91 patients.
      During the 243 hours of insulin infusion therapy, the decline in serum glucose
      was 0 to 100 mg/dL during 162 hours, 101 to 200 mg/dL during 49 hours, 201 to 300
      mg/dL during 8 hours, and more than 300 mg/dL during 3 hours. Of the 193 hours of
      0.05 to 0.1 units/kg/h insulin administration, there were 47 hours (24%) during
      which the serum-glucose decrease was greater than 100 mg/dL. Of the 21 hours of
      insulin administration at less than 0.05 units/kg/h, there was 1 hour (4.8%)
      where the serum-glucose decrease was greater than 100 mg/dL (P = 0.05 vs. insulin
      infusion at 0.05 to 0.1 units/kg/h). Commonly used insulin dosing regimens of a
      bolus of 0.1 units/kg followed by an infusion of 0.05 to 0.1 units/kg/h
      frequently resulted in a decrease in serum glucose of greater than 100 mg/dL/h.
      Prospective trials are needed to more accurately define appropriate insulin
      dosing regimens for pediatric patients with DKA.

PMID- 17515703
TI  - The effects of quinidine and its chiral isolates on erg-1sm potassium current and
      correlation with gastrointestinal augmentation.
AB  - Smooth-muscle erg 1 (erg1-sm) potassium channel has been recently reported to
      participate in the modulation of gastrointestinal contractility. Because
      quinidine inhibits cardiac potassium channel and as a result augments
      gastrointestinal contractility, it was thought that quinidine may affect erg1-sm.
      Studies were undertaken to evaluate the effects of quinidine and its chiral
      isolates on gastrointestinal erg1-sm potassium current and correlate these
      effects with colon contractility. Chiral separation (high-performance liquid
      chromatography technique), mass spectrometry, and optical rotation determination
      were performed to obtain chiral isolates needed for experiments. The erg1-sm
      potassium channel was expressed in Xenopus oocytes, and the two-electrode patch
      clamp technique was employed for recording. An isolated rat colon preparation was
      employed to measure changes in contractility. As a result of chiral separation,
      two peaks were obtained with elution times of 8.31 and 8.66 minutes, both with a
      molecular weight of 324; the optical rotations of racemate isolates X and Y were:
      +258 degrees, +/-0 degrees; and +217 degrees, respectively. The percentage
      changes in amplitudes of colon contraction (from baseline) were determined at
      different concentrations of quinidine and for the two isolates in five
      experiments in each group. Quinidine 0.1, 1, and 10 microM increased
      contractility by 79 +/- 34, 125 +/- 42, and 217 +/- 51 (P < or = 0.05); for
      isolate X, the values were 70 +/- 20, 115 +/- 32, and 272 +/- 32 (P < or = 0.05),
      and for isolate Y the values were 22 +/- 12, 46 +/- 17, and 59 +/- 22. The
      inhibition of erg1-sm currents by quinidine was 19 +/- 4, 21 +/- 5, and 48 +/- 6
      (P < or = 0.05), respectively; that by isolate X was 20 +/- 4, 23 +/- 5, and 39
      +/- 7 (P < or = 0.05), and that by isolate Y was 22 +/- 4, 21 +/- 4, and 31 +/-
      6. One chiral isolate and quinidine markedly augmented contractility, whereas
      quinidine and the two chiral isolates inhibited the erg1-sm potassium currents to
      a similar extent. These results suggest that erg1-sm inhibition does not explain
      gastrointestinal contractile augmentation caused by the quinidine racemate and
      its chiral isolates.

PMID- 17515704
TI  - The average stent length is longer and the average stent diameter is shorter in
      patients with drug-eluting stents versus bare-metal stents during percutaneous
      coronary intervention.
AB  - Drug-eluting stents (DES) were inserted in 180 patients (270 stents), mean age 63
      years, and bare-metal stents (BMS) were inserted in 191 patients (301 stents),
      mean age 63 years, during percutaneous coronary intervention. Baseline
      characteristics were similar for patients treated with DES or BMS. The average
      stent length was longer for DES (16.83 mm) versus BMS (15.45 mm) (P = 0.0026).
      The average stent diameter was shorter for DES (2.89 mm) versus BMS (3.00 mm) (P
      = 0.00027). In-hospital stent thrombosis occurred in one of 270 DES (0.4%) versus
      three3 of 301 BMS (1.0%) (P = not significant).

PMID- 17515705
TI  - Comparative in vitro metabolism of 14C-ciclesonide in hepatocytes from the mouse,
      rat, rabbit, dog, and human.
AB  - The in vitro metabolism of ciclesonide, a novel inhaled nonhalogenated
      glucocorticoid for the treatment of asthma, was compared in cryopreserved
      hepatocytes from mice, rats, rabbits, dogs, and humans. Incubations of C
      ciclesonide with individual hepatocyte suspensions revealed similar metabolite
      profiles in all 5 in vitro systems used. Ciclesonide was rapidly converted to its
      active metabolite, desisobutyryl-ciclesonide (des-CIC). Des-CIC was then
      extensively metabolized to pharmacologically inactive metabolites through
      oxidation and reduction, followed by glucuronidation. A total of 12 groups of
      metabolites derived from des-CIC were characterized and identified by liquid
      chromatography/radioactivity monitor/mass spectrometry. Oxidation occurred on
      both the cyclohexane ring and the steroid moiety. Hippuric acid formation by
      cleavage of the cyclohexylmethyl moiety of ciclesonide, followed by aromatization
      of the cyclohexane ring through multiple steps of hydroxylation, dehydration, and
      conjugation with glycine, was found in rat, rabbit, and human hepatocyte
      incubations. The results indicated that ciclesonide and its active metabolite,
      des-CIC, were extensively metabolized in vitro in animal and human hepatocytes
      and that the metabolite profiles in mouse, rat, rabbit, and dog hepatocytes were
      similar to the profiles in human hepatocytes.

PMID- 17515706
TI  - Emerging therapies for acute ischemic stroke.
AB  - Stroke is a major public health problem in the United States and the development
      of novel therapeutic strategies is an important research priority. Advances in
      this field are proceeding on several fronts, including the use of next-generation
      plasminogen activators and glycoprotein IIb/ IIIa inhibitors, refined patient
      selection with advanced magnetic resonance imaging sequences, endovascular
      approaches to thrombolysis and thrombectomy, and adjuvant use of ultrasound.
      There remains no proven therapy for intracerebral hemorrhage, but early results
      with recombinant activated factor VII look very promising. It is hoped that in
      the near future, physicians managing patients with acute neurological events will
      have a robust armamentarium of therapies to bring to bear on both ischemic and
      hemorrhagic vascular disease.

PMID- 17515707
TI  - Zolpidem extended-release: a single insomnia treatment option for sleep induction
      and sleep maintenance symptoms.
AB  - It is imperative that primary care clinicians have a thorough understanding of
      insomnia, because they are often the first point of contact for patients who seek
      assistance when they have difficulty sleeping. Insomnia may appear with different
      presentations: sleep onset, sleep maintenances, sleep offset, nonrestorative
      sleep, or a combination of these symptoms. Untreated symptoms result in
      clinically significant distress or impairment in social, occupational, or other
      important areas of following-day functionality. Physicians, pharmacists, and
      other clinicians should be aware of the conditions that contribute to, are
      antecedent to, and associated with insomnia. These pathophysiological conditions
      include advanced age; female gender; respiratory, gastrointestinal, vascular, and
      rheumatologic pain syndromes; and other conditions such as depression and/or
      anxiety. Additional health factors contributing to insomnia include chronic pain,
      stressors, grief reaction, pharmacotherapeutic side effects, lifestyle
      contributors such as social/recreational drugs, phytopharmaceuticals, and ethanol
      use. The pharmacotherapy focus in this article is a modified-release formulation
      of the BZ1 (omega1) receptor agonist zolpidem, zolpidem extended-release.
      Pharmacokinetic, pharmacodynamic, and safety studies that compare 12.5 mg
      zolpidem extended-release (Ambien CRtrade markCIV) and 10 mg original zolpidem
      were initially conducted in healthy volunteers to assess the potential for an
      improved clinical profile. Zolpidem extended-release (12.5 mg and 6.25 mg
      extended-release dosage forms) is indicated for the treatment of insomnia
      characterized by difficulties with sleep onset and/or sleep maintenance. Zolpidem
      extended-release is devoid of any short-term use limitation and can be prescribed
      for the duration of medical necessity. The modified-release zolpidem is a two
      layer tablet with a biphasic release profile, releasing the first layer
      immediately, whereas the second layer is released at a slower rate. Plasma
      concentrations are maintained for a longer period of time versus the immediate
      release zolpidem formulation. Pharmacokinetic analysis has also demonstrated that
      the time to maximum concentration (tmax) and terminal elimination half-life
      (t1/2) of 12.5 mg zolpidem extended-release are similar to those of 10 mg
      zolpidem indicating a similar rapid onset of action and an elimination profile
      that reduced the risk of next-day decrements in performance. Zolpidem's CYP 450
      hepatic metabolism uses as a substrate CYP3A4 (major) and 1A2, 2C9, 2C19, and 2D6
      as minor pathways. Zolpidem extended-release dosage forms diminish sleep latency,
      number of awakenings, and wakefulness after sleep onset and augments total time
      asleep.

PMID- 17515708
TI  - Hepatitis B genotypes and response to antiviral therapy: a review.
AB  - The aim of this review is to examine the impact of hepatitis B virus (HBV)
      genotypes on biochemical and virologic response to antiviral drugs (alfa
      interferon and pegylated-interferon alfa-2b, lamivudine, and adefovir dipivoxil)
      actually used for the treatment of chronic hepatitis, HBV related. International
      literature evidences that HBV genotypes D and C are associated with a lower rate
      of favorable response to alfa-interferon and pegylated-interferon alfa-2b therapy
      than genotypes A and B. The rate of resistance to lamivudine was higher in
      patients with genotype A infection than in patients infected by genotype D,
      whereas no difference in the risk of lamivudine resistance is found between
      patients with genotype B and patients with genotype C. In regard to the new
      nucleotide analogue, adefovir dipivoxil, a preliminary trial appears to provide
      no evidence of any difference in virologic response among the different HBV
      genotypes. The current study has determined that the different HBV genotypes have
      a very important impact on response to antiviral therapy, in particular
      interferon treatment. For this reason, determining the HBV genotype could be
      helpful for predicting the outcome of antiviral therapy in patients affected by
      chronic hepatitis B.

PMID- 17515709
TI  - Significant prostate-specific antigen (PSA) response to low-dose ketoconazole in
      a patient with non-metastatic androgen-independent prostate cancer (AIPC) and a
      review of the literature.
AB  - Although there are a variety of treatment options for nonmetastatic androgen
      independent prostate cancer (AIPC), they have limited benefits. Currently, no
      standard of care exists for this population. Ultimately, sequential therapeutics
      can be used to minimize symptomatic progression and control the underlying
      disease, as determined by prostate-specific antigen (PSA) levels. We report here
      a 90-year-old patient who had PSA progression after multiple previous treatments
      and was started on ketoconazole 200 mg, three times daily. His serum PSA levels
      dropped 84% in less than a year on therapy. A literature review yields several
      studies that support the benefits of ketoconazole as noted by PSA reduction and
      correlates these responses with survival benefits. The literature also suggests
      that low-dose ketoconazole may be an appropriate second- or third-line hormonal
      agent in AIPC, causing a PSA decline, symptomatic relief, and minimal toxicity.

PMID- 17515710
TI  - Clozapine-resistant psychosis, smoking, and caffeine: managing the neglected
      effects of substances that our patients consume every day.
AB  - More than 30% of patients with psychotic disorders who are refractory to
      antipsychotic treatment also fail to respond to clozapine. Despite the high
      prevalence of smoking and caffeine use in the psychiatric population, these
      habits are usually overlooked as factors contributing to antipsychotic treatment
      failure. We describe 2 male patients with severe treatment-resistant psychosis,
      one with schizophrenia and the other with bipolar affective disorder-both of whom
      smoked heavily, and the latter also consumed enormous amounts of caffeine-whose
      symptoms were refractory to clozapine. Both patients experienced a major,
      sustained amelioration of their psychotic symptoms when clozapine treatment was
      recommenced under supervision in the inpatient setting and the pharmacological
      interactions between clozapine, smoking, and caffeine were considered.
      Therapeutic strategies included gradual increases in daily doses of clozapine,
      monitoring clozapine plasma levels, using single daily doses of clozapine at
      night, and augmenting clozapine treatment with low doses of amisulpride, a
      selective antagonist at the dopamine D2 and D3 receptors. Smoking and excessive
      caffeine use are associated with poor therapeutic responses to clozapine and
      should be considered in the pharmacological management of treatment-refractory
      psychosis, regardless of the primary diagnosis.

PMID- 17515711
TI  - Prolonged transcutaneous cardiopulmonary support for postcardiotomy cardiogenic
      shock.
AB  - Percutaneous cardiopulmonary support can be set up quickly at the bedside and
      provides reliable temporary mechanical circulatory support for cardiogenic shock
      patients. This report includes the case of a woman, age 56 years, with
      postoperative cardiogenic shock due to right heart failure, secondary to severe
      pulmonary hypertension, after mitral and tricuspid valve replacement. This was
      accomplished by the use of femoro-femoral Levitronix Centrimag centrifugal pump
      with membrane oxygenator. Adequate cardiac function returned, and the patient
      could be successively weaned after 37 days of support. Nitric oxide (NO) and
      Epoprostenol inhalation were used to enhance weaning from cardiopulmonary
      support. The patient recovered with ambulatory status and acceptable cardiac
      performance. The patient died of septicemia on postoperative day 72. In
      conclusion, this case report describes the safety and reliability of the
      Levitronix Centrimag centrifugal pump as percutaneous cardiopulmonary support for
      cardiogenic shock.

PMID- 17515712
TI  - From Baghdad to Germany: use of a new pumpless extracorporeal lung assist system
      in two severely injured US soldiers.
AB  - The authors describe a new extracorporeal pumpless interventional lung assist
      system (iLA) that was implemented in two US soldiers with severe acute
      respiratory distress syndrome received from enemy action in Iraq, who were at
      risk for critical hypoxemia/hypercapnia. The system is characterized by a new low
      resistance gas exchange membrane that is integrated in an arterial-venous bypass
      established by cannulation of the femoral artery and vein. Cardiovascular
      stability is essential to produce sufficiently high blood flow rates over the gas
      exchange unit. After implantation of the interventional lung assist, oxygenation
      increased and carbon dioxide elimination improved rapidly. Ventilator settings
      were able to be adjusted to the decreased pulmonary gas exchange needs, making
      protective lung strategies possible. Air transport of both patients with the
      running iLA system was uneventful. The iLA was removed after 15 and 8 days of
      continuous operation, respectively, and both soldiers were successfully weaned
      from mechanical ventilation. Interventional, extracorporeal pump-free pulmonary
      support opens up new possibilities for pulmonary protection due to ease of use,
      effectiveness, and low costs; however, there is concern of distal limb ischemia.
      Experiences to date are encouraging, although randomized studies are lacking, and
      the procedure carries significant risks.

PMID- 17515713
TI  - Fixation of vascular grafts with increased glutaraldehyde concentration enhances
      mechanical properties without increasing calcification.
AB  - Our objective was to study the effect of glutaraldehyde (GLU) concentration,
      heat, and photooxidation on mechanical properties and calcification of bovine
      pericardium grafts in an in vivo model. Fresh pericardia were treated as follows:
      0.625% GLU for 7 days (standard); 0.625%, 1%, and 3% GLU at 4 degrees C for 20
      days and 50 degrees C for additional 20 days; irradiation in cross-linking medium
      with metilene blue at 0 degrees C for 8 hours. Tissues were subjected to tensile
      mechanical tests (n = 76). Fixed patches were subcutaneously implanted in mice
      for 50 days (n = 16 per treatment). Calcification was assessed by atomic
      absorption spectrophotometry (n = 55) and von Kossa staining (n = 28). Analysis
      of variance and Tukey's test were used for statistical analysis. The 3% GLU and
      3% GLU + heat treatments showed an enhancement of the mechanical properties above
      standard treatment. No significant difference was found in calcification between
      treatments. The 3% GLU treatment enhances the mechanical properties of the tissue
      above standard treatment without increasing calcification and without applying
      heat; therefore it is recommended for high-strength applications. Supplementary
      treatments to decrease calcification could be combined with this methodology to
      obtain a high-strength-low-calcification biomaterial for manufacturing of long
      term cardiovascular grafts.

PMID- 17515714
TI  - Left ventricle load impedance control by apical VAD can help heart recovery and
      patient perfusion: a numerical study.
AB  - The aim of this work is to investigate the dependence between left ventricular
      load impedance control by an apical ventricular assist device (VAD) and the
      consequent benefits for pathological heart recovery. A pathological left
      ventricle with 34% contractility has been simulated in the assisted and
      nonassisted conditions. By means of an extended Kalman filter, left ventricular
      pressure-volume loops have been partially estimated and ventricular as well as
      circulatory quantities inferred. The heart operation mode, based on cardiac
      energetic criteria, is imposed by controlling the VAD filling phase. In the
      assisted condition, results show that the left ventricle end-diastolic volume,
      left atrial pressure, and wall stress all decrease; stroke volume, ejection
      fraction, ventricular efficiency, aortic pressure, and cardiac output all
      increase. Benefits are also evident for the right ventricle and systemic and
      pulmonary circulation. The strategy outlined in this work also shows that good
      results for heart recovery are achievable and a possible way to improve the
      functional properties of commercial pulsatile VADs.

PMID- 17515715
TI  - Mechanical circulatory support for cardiogenic shock complicating acute
      myocardial infarction: an experimental and clinical review.
AB  - Cardiogenic shock (CS) occurs in 7% to 10% of cases after acute myocardial
      infarction and remains the most common cause of death in these patients. Despite
      aggressive treatment regimens such as fibrinolysis and percutaneous transluminal
      coronary angioplasty, mortality rates from CS remain extremely high. It has been
      shown that intra-aortic balloon pumping can result in initial hemodynamic
      stabilization. However, in the majority of studies, death was merely delayed. In
      recent years, efforts have been made to develop ventricular devices (LVAD)
      capable of providing complete short-term hemodynamic support. Seventeen major
      studies of LVAD support for CS complicating acute myocardial infarction are
      reported in the literature, with a mean weaning and survival rate of 58.5% and
      40%, respectively. Patients considered in these studies are difficult to compare
      in terms of demographic and anatomic data, but taking these considerations into
      account, LVAD support seems to give no survival improvement in these patients
      compared with early reperfusion alone or associated with intra-aortic balloon
      pumping. Data emerging from experimental studies of acute myocardial infarction
      supported with LVAD are intriguing. In this review, we report the LVAD experience
      in the CS setting, starting from percutaneous extracorporeal support up to bridge
      therapy with implantable devices.

PMID- 17515716
TI  - Development of the functionally total artificial heart using an artery pump.
AB  - Based on the assumption that only the pump function of the diseased heart should
      be assisted or replaced by device while resecting the native heart is
      unnecessary, the concept of a "functionally total artificial heart (FTAH)" was
      explored. An artery pump (AP) was designed for the FTAH. The fabricated pattern
      of the AP, having an outer diameter of 28 mm and a length of 42 mm, was implanted
      in the position of ascending aorta or pulmonary trunk, joining in series to the
      chambers of the left ventricle or the right ventricle. The total weight of the AP
      pattern is 74 g, and it displaces 29 mL of volume and can achieve 5 L/min against
      100 mm Hg pressure with a speed lower than 10,000 rpm. In mock circulation, two
      APs were connected in series with each other, and their flow rates could
      automatically balance each other. Simulative cardiac output and atria pressures
      can be maintained within a suitable range by properly adjusting the rotational
      speeds of each pump. Because the response of the APs to the pressure alterations
      at their inlets and outlets are similar to that of native heart, no intricate
      regulating mechanism would be necessary. This preliminary study shows that the
      concept of the FTAH is feasible if two APs are simultaneously implanted to
      replace native heart function.

PMID- 17515717
TI  - Effect of direct cardiac compression on left ventricular axial dynamics in sheep.
AB  - The HeartPatch direct cardiac compression device consists of two separate,
      nonsurround patches placed on the left and right ventricular free walls. Although
      the device has been shown to effectively restore circulatory parameters in acute
      heart failure sheep, the impact of device inflation on left ventricular geometry
      is yet to be elucidated. This study used sonomicrometer crystal transducers to
      examine three orthogonal left ventricular dimensions under various cardiac states
      and assessed the feasibility of determining stroke volume from these dimensions.
      Seven sheep (weight, 51 +/- 5 kg) were implanted with six sonomicrometer
      crystals, and a heart patch was placed on each of the ventricles. The crystals
      were positioned to measure anterior-posterior, septal-lateral, and apex-base
      (long-axis) dimensions. Sheep were studied under both awake and anesthetized
      conditions. Septal-lateral shortening was increased with direct cardiac
      compression assist, whereas anterior-posterior and long-axis dimensions were
      either unchanged (awake) or decreased (anesthetized). Estimation of stroke
      volume, using the ellipsoid volume model, correlated well with stroke volume
      measured from an aortic flow probe; however, absolute stroke volumes were lacking
      in agreement.

PMID- 17515718
TI  - Identification of device malfunction in patients supported with the HeartMate XVE
      left ventricular assist system.
AB  - Predicting end-of-life for left ventricular assist devices is important to
      determine timing of device removal. A retrospective analysis was performed on 46
      patients undergoing implantation of the latest HeartMate XVE from July 1, 2003,
      through March 31, 2006. Devices were assessed by analysis of motor current
      waveforms and quantification of the titanium or copper particles within dust
      localized to the driveline vent filter by optical, polarized light, scanning
      electron microscopy, and energy dispersive x-ray spectroscopy. Assessments were
      performed monthly for patients supported > or =330 days or for unexpected device
      alarms. Thirty-one (67%) patients were supported for <330 days and 15 (33%) were
      supported for > or =330 days. No malfunctions occurred in patients supported <330
      days. For patients supported > or =330 days, five had abnormal current waveforms
      or copper and titanium dust localized to the vent filter. One underwent urgent
      transplantation, three underwent device replacement (one death; two ongoing), and
      one is with ongoing support. Of the remaining 10 patients, seven underwent
      transplantation; two remain on device; and one died while on left ventricular
      assist device support. There were no unexpected device failures. Bearing wear of
      the HeartMate XVE is predictable by analysis of current waveforms or titanium and
      copper dust within the vent filter.

PMID- 17515719
TI  - Effect of right ventricular pacing on cardiac apex rotation assessed by a
      gyroscopic sensor.
AB  - To quantify cardiac apex rotation (CAR), the authors recently proposed the use of
      a Coriolis force sensor (gyroscope) as an alternative to other complex
      techniques. The aim of this study was to evaluate the effects of right
      ventricular (RV) pacing on CAR. A sheep heart was initially paced from the right
      atrium to induce a normal activation sequence at a fixed heart rate (AAI mode)
      and then an atrioventricular pacing was performed (DOO mode, AV delay = 60 ms). A
      small gyroscope was epicardially glued on the cardiac apex to measure the angular
      velocity (Ang V). From AAI to DOO pacing mode, an increase (+9.2%, p < 0.05) of
      the maximum systolic twisting velocity (Ang VMAX) and a marked decrease (-19.9%,
      p < 0.05) of the maximum diastolic untwisting velocity (Ang VMIN) resulted. RV
      pacing had negligible effects (-3.1%, p = 0.09) on the maximum angle of CAR,
      obtained by integrating Ang V. The hemodynamic parameters of systolic
      (LVdP/dtMAX) and diastolic (LVdP/dtMIN) cardiac function showed slight variations
      (-3.8%, p < 0.05 and +3.9%, p < 0.05, respectively). Results suggest that cardiac
      dyssynchrony induced by RV pacing can alter the normal physiological ventricular
      twist patterns, particularly affecting diastolic untwisting velocity.

PMID- 17515720
TI  - Design features, developmental status, and experimental results with the
      Heartmate III centrifugal left ventricular assist system with a magnetically
      levitated rotor.
AB  - A long-term left ventricular assist system for permanent use in advanced heart
      failure is being developed on the basis of a compact centrifugal pump with a
      magnetically levitated rotor and single-fault-tolerant electronics. Key features
      include its "bearingless" (magnetic levitation) design, textured surfaces similar
      to the HeartMate XVE left ventricular assist device (LVAD) to reduce
      anticoagulation requirements and thromboembolism, a sensorless flow estimator,
      and an induced pulse mode for achieving an increased level of pulsatility with
      continuous flow assistance. In vitro design verification testing is underway.
      Preclinical testing has been performed in calves demonstrating good in vivo
      performance at an average flow rate of 6 L/min (maximum: >11 L/min) and normal
      end-organ function and host response. Induced pulse mode demonstrated the ability
      to produce a physiological pulse pressure in vivo. Thirteen LVADs have achieved
      between 16 to 40 months of long-term in vitro reliability testing and will be
      continued until failure. Both percutaneous and fully implanted systems are in
      development, with a modular connection for upgrading without replacing the LVAD.

PMID- 17515721
TI  - Preoperative clinical factors are important determinants of the inflammatory
      state before and after heart surgery.
AB  - Postoperative inflammatory response is common in heart surgery patients, but less
      is known about variation in the baseline inflammatory state. This study
      characterizes the preoperative inflammatory profile in a group of high- and low
      risk patients (n = 32; male 16, female 16; mean age, 70.3 +/- 1.8) and relates
      this to postoperative events. Interleukin-6 (IL-6), tumor necrosis factor (TNF)
      alpha, TNF receptors (R1 and R2), and high-sensitivity C-reactive protein were
      measured before surgery and 4 hours after arrival in the intensive care unit.
      Considerable variability existed in all preoperative inflammatory mediators
      before surgery. Patients with an elevated baseline IL-6 level, (IL-6 >10 pg/mL)
      were older (73.5 +/- 2.2 vs. 67.9 +/- 2.6 years), had a lower ejection fraction
      (34 +/- 3.8% vs. 44 +/- 2.9%), a higher predicted risk score (10.3 +/- 1.2 vs.
      5.9 +/- 1.1), and a higher baseline high-sensitivity C-reactive protein (65 +/-
      10 vs. 24 +/- 6 mg/L), p < 0.05 for all. These patients had high morbidity and
      mortality rates after surgery. In addition, patients judged to be at high risk on
      clinical criteria were found to have consistent elevations in the baseline
      inflammatory state. All patients had a surge in inflammatory mediators after
      surgery, but those who started at a higher baseline reached a higher
      postoperative level than the others (IL-6 2023 +/- 561 vs. 361 +/- 47 pg/mL, p <
      0.05). Many heart surgery patients, especially higher-risk patients, have a
      significant inflammatory state before surgery. These patients are at risk for
      high morbidity and mortality rates after surgery.

PMID- 17515722
TI  - Transfusion protocol for implantation and explantation of cardiac devices in an
      academic medical center.
AB  - Few reports in the literature describe the transfusion support needed for
      implantation and explantation of cardiac assist devices. Because such devices are
      frequently used at this institution, we have established a protocol to support
      these patients. We reviewed blood bank records to document the usage of blood
      components in all patients on cardiac assist devices from 1989 to 2005 (n = 215).
      The data were separated into components given at the time of implantation and
      explantation of the device. Implantation data on 214 patients showed the mean use
      as follows: red blood cells (RBC), 5.7 U; platelets (PLT), 2.4 U; fresh frozen
      plasma (FFP), 7.5 U; and cryoprecipitate, 0 U. Explantation data on 134 patients
      showed a mean use as follows: RBC, 7.7 U; PLT, 2.4 U; FFP, 9.9 U; and
      cryoprecipitate, 3.7 U. Our protocol for the preparation of blood components for
      implantation and explantation of a cardiac device is, implantation: RBC, 4 U;
      PLT, 1 U; FFP, 6 U; explantation: RBC, 8 U; PLT, 2 U; FFP, 8 U. Our data do not
      support the need for preparation of cryoprecipitate before implantation or
      explantation.

PMID- 17515723
TI  - Relationship between effect of polymyxin B-immobilized fiber and high-mobility
      group box-1 protein in septic shock patients.
AB  - Direct hemoperfusion (DHP) using a polymyxin B (PMX)-immobilized fiber column has
      been used for treatment of endotoxemia-induced septic shock in Japan since 1994
      and is now an accepted therapy for reducing serum endotoxin levels. Although a
      reduction in inflammatory cytokines has been reported, the detailed mechanism of
      DHP-PMX is not known. We investigated the high-mobility group box-1 (HMGB-1)
      level in septic shock patients treated with DHP-PMX. Subjects (n = 20) were
      separated into two group: those whose systolic blood pressure increased to more
      than 30 mm Hg immediately after DHP-PMX (effective [E] group: nine cases) and
      those whose systolic blood pressure did not increase to more than 30 mm Hg
      (noneffective [N-E] group: 11 cases). The interleukin-6, plasminogen activator
      inhibitor-1, and HMGB-1 levels were measured in each group. The Pao2/Fio2 ratio
      and the Sepsis-Related Organ Failure Assessment (SOFA) score were also evaluated.
      Pretreatment interleukin-6, plasminogen activator inhibitor-1, and HMGB-1 levels
      were similar in the E and N-E groups, but mortality rate was significantly higher
      in the N-E group. Furthermore, posttreatment SOFA score was significantly lower
      in the E group. In the E group, only the HMGB-1 levels improved significantly
      after DHP-PMX. Present data suggest that the circulation dynamics of septic shock
      patients can be improved by reducing HMGB-1 levels by using DHP-PMX.

PMID- 17515724
TI  - Effect of continuous bioartificial kidney therapy on porcine multiple organ
      dysfunction syndrome with acute renal failure.
AB  - The bioartificial kidney (BK) was fabricated with primary culture of human
      proximal tubular cells growing in a hemofilter. A porcine model with multiple
      organ dysfunction syndrome, including acute renal failure, was induced by cecal
      ligation and puncture and bilateral ureteral ligation. The models were treated
      with BK (group A) or sham BK (group B) or without treatment (group C). Mean
      arterial pressure (mm Hg) was higher in group A (88.13 +/- 7.62) than in groups B
      and C (63.50 +/- 11.82, 53.50 +/- 2.52) at 24 hours (p < 0.01). Serum blood urea
      nitrogen, Cr, K, Pao2, and HCO3 were similar during the treatment periods between
      groups A and B, which were better than those in group C. In group A, tumor
      necrosis factor (TNF)-alpha (pg/mL) was 394.42 +/- 35.62 at 24 hours, lower than
      that of groups B and C (531.76 +/- 30.23, 552.89 +/- 27.81) (p < 0.05). Peak
      level of interleukin (IL)-10 (pg/mL) was higher in group A (272.36 +/- 48.89)
      than in groups B and C (106.30 +/- 29.69, 102.59 +/- 10.21) (p < 0.01). There was
      no difference of serum IL-6 between pretreatment and post-treatment in groups A
      and B, but serum IL-6 gradually increased in group C. The survival time (hours)
      was longer in group A than in other groups, which was prolonged by 46.20% and
      58.39%. Results indicate that BK can ameliorate mean arterial pressure, decrease
      serum TNF-alpha, increase serum IL-10, and prolong survival time of pigs with
      multiple organ dysfunction syndrome and acute renal failure.

PMID- 17515725
TI  - Amiloride-sensitive sodium channels on the parietal human peritoneum: evidence by
      ussing-type chamber experiments.
AB  - The mesothelium is part of the peritoneal water and ion transport barrier
      essential for peritoneal dialysis (PD) treatment and has a central role in the
      pathogenesis of peritoneal fibrosis and ultrafiltration failure observed in many
      PD patients. We investigated the effect of amiloride on the transmesothelial
      electrical resistance (RTM) of isolated parietal human peritoneum. Intact sheets
      were obtained from seven patients (three men, four women; mean age, 64 +/- 8
      years). Fourteen peritoneal planar sheets were transferred to the laboratory in
      oxygenated Krebs-Ringer bicarbonate solution at 4 degrees C within 30 minutes
      after removal and mounted in an Ussing-type chamber. Amiloride (10(-3) mol/L)
      added apically (n = 8) caused a rapid rise of the RTM to 24.15 +/- 0.76 [OMEGA]H
      cm2 and a subsequent value persistence (p < 0.05); added basolaterally (n = 6),
      it increased the RTM to 22.66 +/- 0.59 [OMEGA]H cm2 within 1 minute, which
      persisted throughout the experiment. RTM was measured before and serially for 30
      minutes after addition of amiloride. Control RTM was 20.29 +/- 0.86 [OMEGA]H cm2.
      These results indicate a rapid inhibitory effect of amiloride on the ionic
      permeability of parietal human peritoneum. The increase in the RTM observed after
      addition of amiloride clearly indicates the existence of amiloride-sensitive
      sodium channels on the human parietal peritoneal membrane, which may play some
      role in the ultrafiltration process and sodium removal during PD.

PMID- 17515726
TI  - Fluid dynamics during hemodialysis in relationship to sodium gradient between
      dialysate and plasma.
AB  - Fluid shifts during hemodialysis involve changes in both extracellular and
      intracellular volumes. This study aimed to determine the effect of intradialytic
      sodium gradients (GNa), that is, the difference between dialysate and serum
      sodium concentration, on dynamics of extracellular and intracellular volumes in a
      group of maintenance hemodialysis patients. Extracellular volume change
      (deltaECV) between predialysis and postdialysis periods was determined by whole
      body bioimpedance spectroscopy; intracellular volume change (deltaICV) was
      indirectly derived as the difference between deltaECV and the change in body
      weight, corrected for intradialytically given fluids. A total of 200 bioimpedance
      measurements were performed in 32 dialysis patients. Extracellular and
      intracellular volume changes were -2.6 +/- 0.9 L (range: -4.7 to -0.5 L) and -0.2
      +/- 0.7 L (range: -2.5 to +1.5 L), respectively. There was a significant
      correlation between deltaICV and GNa; deltaICV = -0.12 * GNa + 0.26 (p < 0.001).
      In contrast, GNa was not correlated with deltaECV. We conclude that the sodium
      gradient between dialysate and plasma has a significant effect on the ICV during
      dialysis. Hemodialysis with GNa = 0 mmol/L should be sought to prevent ICV
      shrinking or swelling and to prevent excessive thirst, consequently high
      interdialytic weight gains, and ultrafiltration rates.

PMID- 17515727
TI  - Altered proximal aortic stiffness and endothelin plasma levels in diabetic
      patients with end-stage renal disease.
AB  - Peripheral artery stiffness is altered in diabetic patients with end-stage renal
      disease (ESRD), whereas few data exist to confirm this trend for proximal aortic
      stiffness. The pulse wave velocity of the proximal aorta (PWVr) and of the
      carotid-to-femoral aortic segment (PWVcf) were determined by ultrasound imaging
      in 160 patients with ESRD (70 diabetic) and in 160 matched control subjects.
      Also, plasma levels of endothelin, homocysteine, and high-sensitivity C-reactive
      protein were determined in both groups. Patients with ESRD had increased pulse
      pressure, left ventricular (LV) end-diastolic diameter, LV mass index, PWVr, and
      PWVcf compared with control subjects (p < 0.05). Diabetic patients had increased
      LV mass index, PWVr, and PWVcf compared with nondiabetic patients with ESRD (p <
      0.05). Endothelin levels exhibited a strong relation with PWVr (r = 0.32, p <
      0.001) and PWVcf (r = 0.33, p < 0.001) measurements in ESRD patients.
      Multivariate linear regression analysis revealed that age, diabetes, and plasma
      levels of endothelin were major determinants of increased PWVr measurements in
      the total ESRD population. After adjustment for age, body surface area, time on
      dialysis, systolic blood pressure, history of hypertension, and plasma endothelin
      levels, diabetes was an independent factor associated with PWVr in ESRD subjects.
      Diabetic patients with ESRD had significantly increased proximal aortic stiffness
      and significantly altered plasma levels of endothelin as compared with the
      nondiabetic.

PMID- 17515728
TI  - Assessment of temporary dialysis catheter performance on the basis of flow and
      pressure measurements in vivo and in vitro.
AB  - The efficiency of hemodialysis treatments depends on catheter performance and,
      consequently, on effective blood flow that can be achieved at maximum
      extracorporeal pressures. Differences in effective and displayed flow were
      determined with ultrasound dilution technology, and a mathematical correction
      function for the MultiFiltrate hemodialysis machine was developed. This algorithm
      was used to calculate effective blood flow during treatment from displayed flow
      and arterial pressure. To assess catheter performance over time, we measured
      effective blood flow as function of extracorporeal pressure in 11 uncuffed,
      tunneled hemodialysis catheters with shotgun design. Pressure and flow profiles
      of the catheters were determined, and pressure symmetry was measured. To assess
      flow resistance over time, pressure trends of the catheters at different blood
      flow rates were measured for each patient over a mean period of 6.1 +/- 3.0 days.
      Increases in flow resistance during the study period were found to be small. Mean
      arterial pressure decreased from -185 mm Hg to -200 mm Hg, and mean venous
      pressure increased from 197 mm Hg to 215 mm Hg. Effective flow did not change
      significantly during the study. In conclusion, all catheters investigated easily
      provided effective flows above 450 mL/min over the study period at maximum
      extracorporeal pressures below +/-300 mm Hg.

PMID- 17515729
TI  - Effects of relative blood volume-controlled hemodialysis on blood pressure and
      volume status in hypertensive patients.
AB  - In hypertensive hemodialysis (HD) patients, dry weight reduction to normalize
      blood pressure (BP) often results in increased frequency of HD hypotension.
      Because HD with blood volume tracking (BVT) has been shown to improve intra-HD
      hemodynamic stability, we performed a prospective, randomized study to test
      whether BVT is more effective than standard hemodialysis (SHD) in the management
      of hypertension by dry weight reduction. After a run-in period of 4 weeks on SHD,
      28 patients were randomly assigned for a 12-week treatment period with either SHD
      (n = 14) or BVT (n = 14). The mean pre-HD and post-HD weight did not change over
      time in either group. In the BVT group, pre-HD systolic and diastolic BP
      decreased on average 22.5 mm Hg and 8.3 mm Hg, respectively (both p < 0.05),
      whereas BP did not change in the SHD group. Extracellular water and
      cardiothoracic ratio decreased significantly (all p < 0.05) in the BVT group but
      not in the SHD group. Brain natriuretic peptide levels declined only in the BVT
      group, without reaching statistical significance. The frequency of HD hypotensive
      episodes decreased significantly (p < 0.05) in the BVT group and was unchanged in
      the SHD group. HD with BVT was associated with a significant reduction in pre-HD
      BP. At the same time, the frequency of intra-HD hypotensive episodes decreased.
      Although the mean weight did not change, the reductions in cardiothoracic ratio
      and extracellular water suggest that HD with BVT resulted in optimization of
      volume status.

PMID- 17515730
TI  - Presence of plasticizer di-2(ethylhexyl)phthalate in primed extracorporeal
      circulation circuits.
AB  - Many centers advocate the use of a standby wet-primed extracorporeal membrane
      oxygenation (ECMO) circuit for rapid deployment during cardiopulmonary
      resuscitation. However, concerns with regard to the potential health hazards
      associated with the release of the plasticizer di-2(ethylhexyl)phthalate (DEHP)
      from the polyvinyl chloride (PVC) tubing exist. The purpose of this study was to
      determine the time course of DEHP release from a preprimed ECMO circuit and to
      evaluate the effect of PVC tubing coatings on DEHP release. Seven circuits
      including three uncoated (Medtronic, Medtronic with albumin, and Medtronic Super
      Tygon) and four attenuated surfaces (Carmeda, COBE Smart, Medtronic Trillium, and
      Terumo x-coated) were primed with Plasmalyte A. Samples of the circuit prime were
      collected over a period of 2 weeks and were analyzed for DEHP, using gas
      chromatography. Results were compared by using a two-tailed t test. One coated
      (Carmeda) and all three uncoated circuits leached DEHP. The greatest amount of
      leaching occurred in the uncoated Medtronic tubing with albumin. The COBE Smart,
      Medtronic Trillium, and Terumo x-coated circuits had undetectable amounts of DEHP
      (p = 0.006 vs Medtronic uncoated). Prepriming an ECMO circuit composed of
      uncoated PVC tubing is associated with DEHP release. Using coated PVC tubing
      appears to eliminate DEHP release over a 2-week period.

PMID- 17515731
TI  - Evaluation of fiber bundle rotation for enhancing gas exchange in a respiratory
      assist catheter.
AB  - Supplemental oxygenation and carbon dioxide removal through an intravenous
      respiratory assist catheter can be used as a means of treating patients with
      acute respiratory failure. We are beginning development efforts toward a new
      respiratory assist catheter with an insertional size <25F, which can be inserted
      percutaneously. In this study, we evaluated fiber bundle rotation as an improved
      mechanism for active mixing and enhanced gas exchange in intravenous respiratory
      assist catheters. Using a simple test apparatus of a rotating densely packed
      bundle of hollow fiber membranes, water and blood gas exchange levels were
      evaluated at various rotation speeds in a mock vena cava. At 12,000 RPM, maximum
      CO2 gas exchange rates were 449 and 523 mL/min per m2, water and blood,
      respectively, but the rate of increase with increasing rotation rate diminished
      beyond 7500 RPM. These levels of gas exchange efficiency are two- to threefold
      greater than achieved in our previous respiratory catheters using balloon
      pulsation for active mixing. In preliminary hemolysis tests, which monitored
      plasma-free hemoglobin levels in vitro over a period of 6 hours, we established
      that the rotating fiber bundle per se did not cause significant blood hemolysis
      compared with an intra-aortic balloon pump. Accordingly, fiber bundle rotation
      appears to be a potential mechanism for increasing gas exchange and reducing
      insertional size in respiratory catheters.

PMID- 17515732
TI  - Early in vivo experience with the pediatric Jarvik 2000 heart.
AB  - The need for smaller, more efficient ventricular assist devices that can be used
      in a more chronic setting have led to exploration of mechanical circulatory
      support in the pediatric population. The pediatric Jarvik 2000 heart (child
      size), under development, was implanted in six juvenile sheep and studied for
      both acute fit and chronic performance evaluation. Daily hemodynamic measurements
      of cardiac output and pump output at varying pump speeds were taken. In addition,
      plasma free hemoglobin, lactic acid dehydrogenase, and platelet activation from
      blood samples were determined at baseline, after implantation, and twice a week
      thereafter. The measured flow through the outflow graft at increasing speeds from
      10,000 rpm to 14,000 rpm with an increment of 1,000 rpm were 1.47 +/- 0.43, 1.89
      +/- 0.52, 2.36 +/- 0.61, 2.80 +/- 0.73, and 3.11 +/- 0.86 (L/min). The baseline
      plasma free hemoglobin was 11.95 +/- 4.76 (mg/dL), with subsequent mean values
      being <30 mg/dL at postimplantation and weekly postimplantation measurements.
      Both lactic acid dehydrogenase and platelet activation showed an acute increase
      within the first week after implantation with subsequent return to baseline by 2
      weeks after surgery. Our initial animal in vivo experience with the pediatric
      Jarvik 2000 heart shows that a small axial flow pump can provide partial to
      nearly complete circulatory support with minimal adverse effects on blood
      components.

PMID- 17515733
TI  - The effect of left ventricular function and drive pressures on the filling and
      ejection of a pulsatile pediatric ventricular assist device in an acute animal
      model.
AB  - Penn State is currently developing a 12-mL, pulsatile, pneumatically driven
      pediatric ventricular assist device intended to be used in infants. After
      extensive in vitro testing of the pump in a passive-filling, mock circulatory
      loop, an acute animal study was performed to obtain data with a contracting
      ventricle. The objectives were to determine the range of pneumatic pressures and
      time required to completely fill and empty the pediatric ventricular assist
      device under various physiologic conditions, simulate reductions in ventricular
      contractility and blood volume, and provide data for validation of the mock
      circulatory loop. A 15-kg goat was used. The cannulation was achieved via left
      thoracotomy from the left ventricle to the descending aorta. The pump rate and
      systolic duration were controlled manually to maintain complete filling and
      ejection. The mean ejection time ranged from 280 ms to 382 ms when the systolic
      pressure ranged from 350 mm Hg to 200 mm Hg. The mean filling time ranged from
      352 ms to 490 ms, for the diastolic pressure range of -60 mm Hg to 0 mm Hg.
      Esmolol produced a decrease in left ventricular pressure, required longer pump
      filling time, and reduced LVAD flow.

PMID- 17515734
TI  - Effect of continuous and pulsatile flow left ventricular assist on pulsatility in
      a pediatric animal model of left ventricular dysfunction: pilot observations.
AB  - Pediatric ventricular assist devices are being developed that can produce
      pulsatile flow (PF) or continuous flow (CF). An important aspect of choosing
      between these two modes is understanding the consequences of each mode on
      pediatric vascular pulsatility. Differences in vascular pulsatility generated by
      PF and CF operation of the 3-inch pediatric cardiopulmonary assist system (pCAS,
      Ension, Inc., Pittsburgh, PA) were investigated while providing left atrium-to
      aorta left ventricular assist (LVA), using an infant animal model of left
      ventricular dysfunction. Hemodynamic data were digitally recorded with the pCAS
      providing LVA at incremental flow rates while operating in continuous mode,
      pulsatile mode at 100 bpm, and pulsatile mode at 140 bpm. These data were used to
      calculate vascular input impedance (Zart), energy equivalent pressure, and
      surplus hemodynamic energy as indices of pulsatility for partial (50% of maximum)
      and maximum LVA flow. Both CF and PF LVA by the pCAS resulted in favorable
      hemodynamic rectification of left ventricular dysfunction while generating
      equivalent flows. PF LVA maintained a greater degree of pulsatility compared with
      CF, as evidenced by increasing energy equivalent pressure and a lesser drop in
      surplus hemodynamic energy with increasing pCAS flow. Differences in Zart modulus
      and phase were indiscernible. The selection of flow mode may have long-term
      consequences on Zart and end-organ perfusion affecting clinical outcomes in
      pediatric patients.

PMID- 17515735
TI  - Preclinical testing of the Levitronix Ultramag pediatric cardiac assist device in
      a lamb model.
AB  - We evaluated the effects of the Levitronix UltraMag pediatric ventricular assist
      system on healthy animals during 29- to 90-day periods by assessing
      hemocompatibility and hepatic and renal functions while operating the device in a
      flow range suitable for pediatric patients. Nine lambs (weight, 15 to 24 kg)
      received the Levitronix UltraMag with an outflow cannula anastomosed to the
      descending aorta and an inflow cannula inserted into the left ventricular apex.
      Pump function data were collected at 1-hour intervals, and postoperative
      hematology and clinical chemistry tests were performed weekly throughout the
      study. Complete necropsy and histopathologic examinations were performed at study
      termination. Pump and circuit were thoroughly inspected for evidence of thrombi.
      All animals reached the scheduled endpoint of 29 to 90 days without device
      related problems. Mean flow was maintained at 1.14 +/- 0.19 L/min. Hematologic
      values were within normal range in all animals except in one lamb that had a
      severe hemolytic reaction after cefazolin sodium administration. In all animals,
      serum glutamic-oxaloacetic transaminase and creatinine kinase levels increased
      after surgery but gradually returned to normal limits within 1 week. Postmortem
      examination of the explanted organs revealed small infarcted areas in five lamb
      kidneys, but renal function was unaffected. All other major organs were
      unremarkable. In one explanted pump (a 30-day study), a small thrombus was seen
      within the impeller blade. The other eight pumps were free of thrombus. The
      Levitronix UltraMag successfully operated in pediatric flow ranges without device
      related adverse events.

PMID- 17515736
TI  - Spinal cord injury pain: the influence of psychologic factors and impact on
      quality of life.
AB  - OBJECTIVES: To examine chronic pain prevalence in a spinal cord injury (SCI)
      population, and to determine the influence of psychologic factors on SCI pain and
      impact of SCI pain on quality of life. METHODS: Five hundred seventy-five persons
      with SCI were asked to participate in the study. Demographic, SCI, and pain
      characteristics were obtained. The Chronic Pain Grade, anger items of the Profile
      of Mood States, Illness Cognition Questionnaire, Pain Coping and Cognition List,
      and Patient Health Questionnaire were used. General health and well-being were
      assessed with 0-10 scales. The influence of psychologic factors was assessed with
      regression analyses controlling for person and injury characteristics and pain
      intensity. RESULTS: Response rate was 49%. SCI pain prevalence was high (77.1%).
      More internal pain control and coping, less catastrophizing, higher level of
      lesion, and nontraumatic SCI cause were associated with less pain intensity. More
      pain was associated with higher pain-related disability. Lower catastrophizing
      was related to better health. Less SCI helplessness and catastrophizing, greater
      SCI acceptance and lower anger levels were related to higher well-being. Higher
      levels of SCI helplessness, catastrophizing, and anger were related to higher
      depression levels. Pain intensity showed no independent relationships with
      health, well-being, and depression in the regression analyses. DISCUSSION:
      Chronic SCI pain and quality of life were both largely associated with several
      psychologic factors of which pain catastrophizing and SCI helplessness were most
      important. Psychologic intervention programs may be useful for persons suffering
      from chronic SCI pain to improve their quality of life.

PMID- 17515737
TI  - Parental pain expectancy as a mediator between child expected and experienced
      procedure-related pain intensity during painful medical procedures.
AB  - OBJECTIVES: The aim of this prospective investigation was to evaluate child and
      parental expectancies as a predictor of pain perception in pediatric oncology
      patients undergoing painful medical procedures. METHODS: Forty-five children with
      leukemia or non-Hodgkin lymphoma and their parents rated expected and experienced
      pain during lumbar punctures at baseline, during intervention (ie, cognitive
      behavior therapy) administered by a therapist and when children were using
      cognitive-behavior therapy skills independently. RESULTS: Parental and child
      expectancies were significantly correlated. Parents consistently expected their
      children to experience more pain than children were expecting themselves.
      Parental expectancy was found to mediate the relationship between child expected
      and experienced pain during every phase of the study. DISCUSSION: It is concluded
      that parental expectancies are reliable predictors of pediatric procedure-related
      pain and possible useful targets for psychologic interventions to manage such
      pain.

PMID- 17515738
TI  - Frequency and priority of pain patients' health care use.
AB  - BACKGROUND: Increased health care use by pain patients is largely due to
      conditions other than their identified pain condition, but the kinds of services
      accounting for increased service use are poorly understood. This study assesses
      reasons for health care visits of pain patients versus controls, and compares
      characteristics of pain patients who differ in frequency and priority of service
      use. METHODS: The study samples included consecutive, primary care back pain
      (N=807), headache (N=831), and temporomandibular disorder pain (N=372) patients
      who were interviewed by telephone. Subsequently, age-sex matched controls with a
      primary care visit in the 6 months before the matched case's pain visit were
      identified. Over the following 3 years, diagnostic codes for health care visits
      were classified based on the Oregon Prioritized List of Health Services and case
      control differences in major classes of care were compared. Pain patients
      differing in frequency and priority of service use were compared on measures of
      pain severity, chronicity, and psychosocial dysfunction. RESULTS: Pain patients'
      increased health care use was sustained over 3 years. Increased utilization was
      largely due to symptomatic and ill-defined conditions, lower priority chronic
      disease, lower and higher priority acute disease, and mental health care. About
      one-half of the pain patients (vs. one-third of the controls) were frequent
      health care users. About one-third of the pain patients (vs. one-sixth of the
      controls) were frequent users who predominantly used medical care for lower
      priority conditions, and this difference accounted for most of the case-control
      difference in the prevalence of high users. Pain patients with frequent health
      care use had more severe pain and greater psychosocial dysfunction than pain
      patients with less frequent health care use. Among frequent users, pain patients
      who predominantly used services for lower priority conditions did not differ on
      measures of pain severity, chronicity, or somatization when compared with
      frequent users who typically used services for higher priority conditions.
      CONCLUSIONS: The kind of problems explaining heightened service use of pain
      patients is more varied and complex than previously understood. These results
      call for increased attention to the implications of health care providers
      responding to presenting complaints as if each were a unique problem, without
      bringing continuity or an integrating perspective to patients' overall experience
      and management of illness.

PMID- 17515739
TI  - Shared and independent associations of psychosocial factors on work status among
      men with subacute low back pain.
AB  - OBJECTIVES: Psychosocial variables are acknowledged predictors of back
      disability, but multivariate studies are needed to understand their independent
      and overlapping effects. The objective of this prospective cohort study was to
      evaluate independent and shared associations of psychosocial variables on work
      status after first onset of low back pain (LBP) in working men. METHODS: One
      hundred forty male military personnel reporting subacute, first onset LBP (2 mo
      average duration) completed an interview-based and survey-based psychosocial
      assessment within the domains of job satisfaction, stress and coping, pain
      perceptions and beliefs, perceived functional disability, and mood disturbance.
      Work status was assessed at baseline, 6 and 12-month postpain onset. RESULTS: In
      logistic regression analyses at baseline, work status was associated with pain
      interference and perceptions of physical impairment. Beyond 2 months, the extent
      to which pain was believed to interfere with function was the only significant
      predictor of subsequent changes in work status. Job dissatisfaction was
      associated with more impaired work status, but not after controlling for income.
      Depressive and anxious mood symptoms were prevalent but failed to explain
      additional variance in work status. DISCUSSION: After first onset of men with
      subacute LBP, self-reported pain intensity and functional limitation account for
      most of the variance in work status explained by psychosocial factors; however,
      the resulting disability can be accompanied by mild to moderate mood symptoms.
      This suggests that interventions to improve function, if commenced early in the
      course of subacute pain, might prevent work disability.

PMID- 17515740
TI  - Neonatal facial coding system scores and spectral characteristics of infant
      crying during newborn circumcision.
AB  - OBJECTIVE: To determine the relations between Neonatal Facial Coding System
      (NFCS) scores and measures of infant crying during newborn circumcision. METHODS:
      Video and audio recordings were made of infant facial activity and cry sounds,
      respectively, during the lysis phase of circumcisions of 44 healthy term males
      (<3 d of age). All infants received topical analgesia before circumcision. NFCS
      scores were determined by blinded assistant from video recordings of facial
      activity. Measures of infant crying were determined via spectrum analysis of
      audio recordings by a blinded, independent researcher. Pearson product-moment
      correlations were used to examine relationship between NFCS scores and measures
      of crying. Principal component factor analysis detected dimensions underlying
      related measures of crying. Factor scores from a factor analysis were used in
      stepwise linear regression to predict NFCS scores. RESULTS: Higher NFCS scores
      correlated with lower peak fundamental frequency of crying (P<0.01) and with
      higher amplitudes of crying at peak fundamental frequency and dominant frequency
      and in overall cry sample (P<0.01). The factor analysis showed 3 significant
      orthogonal dimensions underlying measures of crying: Power and Velocity
      (amplitude and rapidity), Pitch of Crying (frequency characteristics), and Infant
      Arousal (turbulence and intensity) accounting for 42.3%, 17.8%, and 14.6% of
      variance, respectively. A regression analysis showed all 3 factor scores
      accounted for significant and separate portions of variance (P<0.001). The best
      predictor of NFCS score was Power and Velocity (P<0.002), followed by Infant
      Arousal (P<0.002), and Pitch of Crying (P<0.007). DISCUSSION: These data provide
      some of the first known evidence linking specific measures of infant crying with
      an independent, validated measure of pain.

PMID- 17515741
TI  - Treatment of painful osteoporotic or traumatic vertebral compression fractures by
      percutaneous vertebral augmentation procedures: a nonrandomized comparison
      between vertebroplasty and kyphoplasty.
AB  - OBJECTIVE: Vertebroplasty (PV) and balloon kyphoplasty (KP) are minimally
      invasive vertebral augmentation procedures involving injection of polymethyl
      methacrylate cement under radiologic control into a fractured vertebral body.
      They strengthen the bone and improve the intense pain caused by fracture
      secondary to osteoporosis, metastasis, or trauma and refractory to conservative
      therapies such as analgesic use, bed rest, and bracing. Aim of the study is to
      investigate and compare safety and efficacy of KP and PV on pain and mobility in
      patients with vertebral fractures due to osteoporosis or trauma. METHODS: Twenty
      one patients have been enrolled in a prospective nonrandomized controlled study
      with painful vertebral compression fractures resistant to common therapies.
      Patients underwent KP or PV. A Visual Analog Scale has been used to measure pain
      status at different time up to 6 months; the Oswestry Disability Index (ODI) was
      chosen to evaluate functional activity before procedure and 6 months later.
      RESULTS: Mean pain scores decreased significantly from pretreatment to
      posttreatment with KP and PV as did the ODI scores. No significant differences
      could be found between both groups for the mean VAS and ODI scores preprocedure
      and postprocedure. Cement extravasation occurred only during PV. No other adverse
      events correlated to both techniques have been reported. DISCUSSION: Our results
      suggest that both PV and KP offer therapeutic benefit significantly reducing pain
      and improving mobility in patients with vertebral fracture without significant
      differences between groups in term of quality. The leakage of cement has been
      observed only during PV.

PMID- 17515742
TI  - Naprapathic manual therapy or evidence-based care for back and neck pain: a
      randomized, controlled trial.
AB  - OBJECTIVES: To compare naprapathic manual therapy with evidence-based care for
      back or neck pain regarding pain, disability, and perceived recovery. Naprapathy
      that is common in the Nordic countries and in some states in the United States is
      characterized by manual manipulations with a focus on soft and connective
      tissues, aiming to decrease pain and disability in the musculoskeletal system.
      METHODS: Four hundred and nine patients with pain and disability in the back or
      neck lasting for at least 2 weeks, recruited at 2 large public companies in
      Sweden in 2005, were included in this randomized controlled trial. The 2
      interventions were naprapathy, including spinal manipulation/mobilization,
      massage, and stretching (Index Group) and support and advice to stay active and
      how to cope with pain, according to the best scientific evidence available,
      provided by a physician (Control Group). Pain, disability, and perceived recovery
      were measured by questionnaires at baseline and after 3, 7, and 12 weeks.
      RESULTS: At 7-week and 12-week follow-ups, statistically significant differences
      between the groups were found in all outcomes favoring the Index Group. At 12
      week follow-up, a higher proportion in the naprapathy group had improved
      regarding pain [risk difference (RD)=27%, 95% confidence interval (CI): 17-37],
      disability (RD=18%, 95% CI: 7-28), and perceived recovery (RD=44%, 95% CI: 35
      53). Separate analysis of neck pain and back pain patients showed similar
      results. DISCUSSION: This trial suggests that combined manual therapy, like
      naprapathy, might be an alternative to consider for back and neck pain patients.

PMID- 17515743
TI  - Central modulation of pain evoked from myofascial trigger point.
AB  - OBJECTIVES: Low-intensity low-frequency electrostimulation delivered within a
      myofascial trigger point (MTP) has been used as intervention to deactivate MTPs.
      The therapeutic effect has been suggested to be due to peripheral mechanisms.
      However, nonpainful stimuli are also known to reduce simultaneous pain through
      central effects. The primary objective of the present study was to assess if
      central pain modulation occurs after intervention with low-intensity
      electrostimulation within an MTP. We hypothesized that intervention induces pain
      inhibition via the periaqueductal gray (PAG). METHODS: Twenty-four patients with
      myofascial pain syndrome participated in the study. During functional magnetic
      resonance scanning, painful (high-intensity) intramuscular electrostimulation was
      delivered at random intervals (mean interstimulus interval=10.2 s) within an MTP
      of the upper left trapezius muscle. In-between scanning sessions, intervention
      (intramuscular electrostimulation, low-intensity, interstimulus interval=0.5 s)
      was applied to the same area. Patients were divided into responders and
      nonresponders according to their change in pressure pain thresholds relative to
      intervention. In addition to a whole brain search, a region of interest approach
      was also implemented to test the effect of intervention on PAG signal change.
      RESULTS: The main findings were: (1) intervention modulated PAG activity to
      painful stimuli more in responders than in nonresponders, (2) change in PAG
      activity from the whole patient population correlated with change in pressure
      pain threshold, and (3) a network known to regulate affective qualities of the
      pain experience was (subsignificantly) engaged more in responders than in
      nonresponders. DISCUSSION: The applied intervention most likely involves
      supraspinal pain control mechanisms related to both antinociception and
      regulation of pain affect.

PMID- 17515744
TI  - Imaging in early posttraumatic complex regional pain syndrome: a comparison of
      diagnostic methods.
AB  - OBJECTIVES: The complex regional pain syndrome type I (CRPS I) still is difficult
      to diagnose in posttraumatic patients. As CRPS I is a clinical diagnosis the
      characteristic symptoms have to be differentiated from normal posttraumatic
      states. Several diagnostic procedures are applied to facilitate an early
      diagnosis, although their value for diagnosing posttraumatic CRPS I is unclear.
      METHODS: One hundred fifty-eight consecutive patients with distal radial fracture
      were followed up for 16 weeks after trauma. To assess the diagnostic value of the
      commonly applied methods a detailed clinical examination was carried out 2, 8,
      and 16 weeks after trauma in conjunction with bilateral thermography, plain
      radiographs of the hand skeleton, three phase bone scans (TPBSs), and contrast
      enhanced magnetic resonance imaging (MRI). All imaging procedures were assessed
      blinded. RESULTS: At the end of the observation period 18 patients (11%) were
      clinically identified as having CRPS I and 13 patients (8%) revealed an
      incomplete clinical picture which were defined as CRPS borderline cases. The
      sensitivity of all diagnostic procedures used was poor and decreased between the
      first and the last examinations (thermography: 45% to 29%; TPBS: 19% to 14%; MRI:
      43% to 13%; bilateral radiographs: 36%). In contrast a high specificity was
      observed in the TPBS and MRI at the eighth and sixteenth-week examinations (TPBS:
      96%, 100%; MRI: 78%, 98%) and for bilateral radiographs 8 weeks after trauma
      (94%). The thermography presented a fair specificity that improved from the
      second to the sixteenth week (50% to 89%). DISCUSSION: The poor sensitivity of
      all tested procedures combined with a reasonable specificity produced a low
      positive predictive value (17% to 60%) and a moderate negative predictive value
      (79% to 86%). These results suggest, that those procedures cannot be used as
      screening tests. Imaging methods are not able to reliably differentiate between
      normal posttraumatic changes and changes due to CRPS I. Clinical findings remain
      the gold standard for the diagnosis of CRPS I and the procedures described above
      may serve as additional tools to establish the diagnosis in doubtful cases.

PMID- 17515745
TI  - Adolescent autonomy and family functioning are associated with headache-related
      disability.
AB  - OBJECTIVES: The aims of this study were to examine the relationships between a
      range of family factors, including autonomy and general family functioning, on
      headache outcomes (ie, pain and functional impairment) in adolescents with
      recurrent headaches. METHODS: Forty nine adolescents, ages 11 to 16 years, (mean
      age=13.5 y, 63% female) receiving treatment through pediatric neurology for
      recurrent headaches were enrolled. Adolescents and their parents completed
      measures of pubertal status, pain, functional impairment, parental
      solicitousness, behavioral autonomy, depressive symptoms, and family functioning.
      RESULTS: Lower levels of adolescent autonomy (r=0.53, P<0.01) and less healthy
      family functioning (r=0.32, P<0.01) were significantly related to higher levels
      of functional impairment. In multivariate regression analyses controlling for
      pain intensity, pubertal status, and depressive symptoms, parent and family
      variables added significant variance in the prediction of functional impairment
      (r change=0.21, P<0.05). Both adolescent autonomy (beta=0.38, P<0.05) and general
      family functioning (beta=0.34, P<0.05) were significant individual predictors of
      adolescent functional impairment. DISCUSSION: This study extends research on
      family factors and adolescent headache-related pain and disability. Future
      research is needed to discover whether family based interventions helping
      adolescents to acquire appropriate and supportive levels of autonomy may be
      useful in reducing headache-related disability.

PMID- 17515746
TI  - Marijuana use in chronic pain patients.

PMID- 17515747
TI  - Impact of PET/CT in comparison with same day contrast enhanced CT in breast
      cancer management.
AB  - PURPOSE: To evaluate the impact of F-18 fluorodeoxyglucose (FDG) positron
      emission tomography with fused computerized tomography (PET/CT) in comparison
      with same day contrast enhanced CT (CE-CT) in breast cancer management. METHOD:
      Seventy studies in 49 breast cancer patients, 17 for initial and 53 for restaging
      disease were included. All patients underwent PET/CT for diagnostic purposes
      followed by CE-CT scans of selected body regions. PET/CT was started
      approximately 90 minutes following IV injection of 10-15 mCi of F-18 FDG on a GE
      Discovery PET/CT system. Oral contrast was given before F-18 FDG injection. The
      CE-CT was performed according to departmental protocol. RESULTS: Out of a total
      of 257 lesions, 210 were concordant between PET/CT and CE-CT. There were 47
      discordant lesions, which were verified by either biopsy (35) or follow-up (12
      PET positive CE-CT negative lesions). PET/CT correctly identified 25 true
      positive (TP). CE-CT identified 2 TP lesions missed by PET/CT which were false
      negatives (FNs): one liver metastasis with necrosis, which was nonavid to FDG
      uptake because of necrosis and a second one missed on abdominal metastatic node,
      which did not change staging or treatment. PET/CT incorrectly identified 2 false
      positive lesions while CE-CT incorrectly identified 18 false positive. TP
      recurrence of the disease was found by PET/CT in 44% (15/34 pts), whereas 56%
      (19/34 pts) were free of disease. The CE-CT described progression of the disease
      in 1 true negative PET/CT study and no progression in 2 TP PET/CT studies. The
      sensitivity, specificity, accuracy, positive productive value, and negative
      productive value for PET/CT were 97.8%, 93.5%, 97.3%, 99.1%, 85% and for CE-CT
      were 87.6%, 42%, 82.1%, 91.6%, 31.7%. CONCLUSION: In this study, PET/CT played a
      more important role than CE-CT scans alone and provided an impact on the
      management of breast cancer patients.

PMID- 17515748
TI  - The prospect of incidental detection of unsuspected skeletal tuberculosis by bone
      scintigraphy should not be overlooked.
AB  - BACKGROUND: The potential roles of bone scintigraphy in the evaluation of
      tuberculosis are not well-defined. It is commonly considered that skeletal
      tuberculosis occurs only after pulmonary tuberculosis. Bone scintigraphy was not
      known to be an effective imaging modality in the evaluation of skeletal
      tuberculosis, especially in those without known systemic tuberculosis. PURPOSE:
      To assess the prospect of bone scintigraphy in the detection of skeletal
      tuberculosis in patients who came to the department of nuclear medicine to
      evaluate back pain. METHODS: Patient records and the images of 1817 cases of
      consecutive bone scintigraphy performed for the evaluation of unknown causes of
      back pain were retrospectively reviewed. The imaging findings were compared with
      the status of tuberculosis before and after scintigraphy. RESULTS: Sixteen
      patients had skeletal tuberculosis confirmed by histopathological examination.
      Six patients had solitary while 10 had multifocal skeletal lesions. Before bone
      scintigraphy, 2 patients were suspected but not confirmed to have pulmonary
      tuberculosis, 4 were suspected to have skeletal tuberculosis by other modalities
      while the remaining 10 patients were not suspected to have tuberculosis in any
      part of the body. Following bone scintigraphy, among those 10 patients who were
      unsuspected of having tuberculosis, further tests demonstrated that 3 had
      pulmonary tuberculosis in addition to skeletal tuberculosis and 1 had cervical
      tuberculous lymphadenitis. In total, among those 16 patients with confirmed
      skeletal tuberculosis, only 6 had concurrent extraskeletal tuberculosis while 10
      patients had their tuberculosis limited to the skeletal system. CONCLUSIONS: Our
      results indicate that pulmonary or systemic tuberculosis is not a prerequisite
      for skeletal tuberculosis. Skeletal tuberculosis should be among the differential
      diagnoses when there is a positive bone scan in patients without a malignancy in
      an endemic region.

PMID- 17515749
TI  - Papillary thyroid carcinoma: 35-year outcome and prognostic factors in 1858
      patients.
AB  - BACKGROUND AND AIM: Papillary thyroid carcinoma (PTC) is universally regarded as
      a curable malignancy with a favorable prognosis. However, a minority of patients
      may present, or subsequently develop, locoregional and distant metastases that
      may adversely affect survival. The value of the various staging methods is
      complicated by different approaches to diagnostic, therapeutic and follow-up
      strategies. We aimed at assessing the prognostic factors and survival rate in a
      large cohort of patients treated and followed up in the same center. MATERIALS
      AND METHODS: A total of 1858 patients with PTC operated on by the same surgeon,
      and followed in the same center over a period of 35 years, were included. Total
      thyroidectomy was performed in the majority of patients after I-131 diagnostic
      scans and thyroglobulin assays. When the latter 2 were positive, therapy with I
      131 was given. Follow-up was performed periodically and further therapy doses
      were administered when necessary. All patients were maintained on life-long
      thyroxine. RESULTS: Ninety-three patients (5%) developed evidence of locoregional
      or distant metastases after an average follow-up period of 7.9 years (range 1.53
      30.5 years). Univariate analysis showed all variables (except for gender) to be
      significantly correlated with disease recurrence and survival. Multivariate
      analysis showed 4 variables to be significant and independent prognostic factors:
      patient age at first treatment, extent of disease, extent of surgery, and the
      presence of I-131 positive metastases. DISCUSSION AND CONCLUSION: Our data agree
      with other scoring systems in that patient age at first treatment and the extent
      of disease are significant and independent prognostic factors. However, and at
      variance with other methods, we found that the extent of primary surgery and the
      presence of I-131 positive or negative metastases have similar prognostic
      significance. In high risk patients, total thyroidectomy and lymphadenectomy
      followed by I-131 treatment and TSH-suppressive hormonal therapy are recommended.

PMID- 17515750
TI  - Cerebellar vermis relative hypermetabolism: an almost constant PET finding in an
      injured brain.
AB  - Cortical alterations of brain metabolism, as seen in PET, obviously depend on the
      nature of the damage (either mechanical, toxic, anoxic, or other). However, some
      subcortical abnormalities seem to occur rather frequently regardless of the
      extension, position and cause of the damage. In particular, relative cerebellar
      vermis activation seems to be frequently encountered. The aim of this work was to
      determine the incidence of this pattern in a heterogeneous population of brain
      trauma, and to compare it on a quantitative basis with a group of age-sex matched
      controls. The case records of this study consist of 58 consecutive patients, 44
      males, 14 females, age 14-69 (median 34) 44 traumatic, 8 anoxic, 4 vascular and 2
      toxic injuries. In the trauma group, the visualization of the cerebellar vermis
      was readily appreciable as a consistent majority of cases. In particular, the
      mean vermis/cerebellum ratio (calculated by appropriate ROI positioning) was 1.26
      +/- 0.17 SD (range 0.92-1.82); in the control group the same parameters showed
      much less dispersion: average 0.92 +/- 0.06, range 0.80-1.10 (P < 0.005). If, on
      the basis of the normal group data, a cut-off value of 1 is accepted for the v/c
      ratio, it is noted that 54/57 trauma patients (95%) showed a ratio above this
      value. In conclusion, a hypermetabolic cerebellar vermis is a common finding in a
      damaged brain, regardless of the nature of the trauma (probably due to the
      relative preservation compared with other structures of alternative metabolic
      pathways), and seems to be the hallmark of the injured brain.

PMID- 17515751
TI  - Dopamine transporter binding in smokers and nonsmokers.
AB  - PURPOSE: Regional brain concentrations of dopamine transporters have been
      examined to elucidate the neurochemical substrates of neurologic and psychiatric
      conditions. Many of these conditions are associated with increased (or decreased)
      cigarette smoking prevalence; therefore, current smoking may confound the results
      of these investigations. This study determined whether healthy current smokers
      and nonsmokers exhibit differences in dopamine transporter (DAT) binding measured
      by Tc-99m TRODAT SPECT. MATERIALS AND METHODS: Tc-99m TRODAT SPECT brain scans
      were retrospectively evaluated in 46 nonsmokers and 8 current smokers, all of
      whom had been recruited and screened as healthy controls for previous imaging
      studies. The scans were acquired approximately 3 hours after the intravenous
      administration of 740 MBq (20 mCi) of Tc-99m TRODAT and were reconstructed with a
      simple bandpass filter. Regions of interest (ROIs) were placed manually on
      subregions of the right and left basal ganglia and distribution volume ratios
      (DVRs) were compared for the smoker and nonsmoker groups. RESULTS: There were
      significant decreases in DAT binding in current smokers compared with nonsmokers
      in the caudate nuclei bilaterally, the right anterior putamen and the left
      posterior putamen. CONCLUSION: Reduced DAT binding in ROIs relevant to movement
      disorders as well as other neuropsychiatric conditions may have important
      implications for evaluating scans in these patient populations.

PMID- 17515752
TI  - Incidental finding of subacute hematoma on PET/CT following cardiac
      catheterization.

PMID- 17515753
TI  - A patient with peripheral arterial stenosis diagnosed with lower extremity
      perfusion scintigraphy.

PMID- 17515754
TI  - Dramatic movement of a Meckel's diverticulum on Tc-99m pertechnetate imaging.

PMID- 17515755
TI  - F-18 fluorodeoxyglucose uptake in a benign gastric ulcer.

PMID- 17515756
TI  - Utility of SPECT/CT in preoperative planning for sentinel lymph node biopsy in
      melanoma and head/neck carcinoma: three illustrative cases.

PMID- 17515757
TI  - Follow-up of a carcinoid tumor in the middle ear by in-111 pentetreotide
      scintigraphy.

PMID- 17515758
TI  - Misleading steal phenomenon of Ga-67 uptake by the spleen in a patient with
      sarcoidosis.

PMID- 17515759
TI  - F-18 FDG uptake due to acinetobacter infection causing misinterpretation of
      treatment response in a lymphoma patient.

PMID- 17515760
TI  - F-18 FDG PET imaging of cervical tuberculous lymphadenitis.

PMID- 17515761
TI  - Disseminated cryptococcosis: detection by F-18 FDG PET.

PMID- 17515762
TI  - FDG-PET imaging in the investigation of homonymous hemianopia in a patient with
      MELAS syndrome.

PMID- 17515763
TI  - Super scan in a patient with diffuse bone metastases from intracranial glioma.

PMID- 17515764
TI  - Positive Tc-99m TRODAT findings in Japanese encephalitis.

PMID- 17515765
TI  - A rare case of MALT lymphoma with Hashimoto's thyroiditis: differential diagnosis
      of cold nodules on Tc-99m pertechnetate thyroid scan.

PMID- 17515766
TI  - Metastatic parotid tumor: a rare presentation for papillary carcinoma of thyroid.

PMID- 17515767
TI  - F-18 FDG PET as an imaging tool for detecting and staging metastatic basal-cell
      carcinoma.

PMID- 17515768
TI  - PET, CT, and MR imaging of extra-articular pigmented villonodular synovitis.

PMID- 17515769
TI  - F-18 FDG uptake in osteonecrosis mimicking bone metastasis on PET/CT images.

PMID- 17515770
TI  - F-18 FDG PET-CT in a rare case of Bartholin's gland undifferentiated carcinoma
      managed with chemoradiation and interstitial brachytherapy.

PMID- 17515771
TI  - Metatarsal metastasis from lung cancer read as a benign process on Tc-99m MDP
      scintigraphy.

PMID- 17515773
TI  - Health care quality and multimorbidity: the jury is still out.

PMID- 17515774
TI  - Multimorbidity is associated with better quality of care among vulnerable elders.
AB  - BACKGROUND: Older patients with multiple chronic conditions may be at higher risk
      of receiving poorer overall quality of care compared with those with single or no
      chronic conditions. Possible reasons include competing guidelines for individual
      conditions, burden of numerous recommendations, and difficulty implementing
      treatments for multiple conditions. OBJECTIVES: We sought to determine whether
      coexisting combinations of 8 common chronic conditions (hypertension, coronary
      artery disease, chronic obstructive pulmonary disease, osteoarthritis, diabetes
      mellitus, depression, osteoporosis, and having atrial fibrillation or congestive
      heart failure) are associated with overall quality of care among vulnerable older
      patients. MATERIALS AND METHODS: Using an observational cohort study, we enrolled
      372 community-dwelling persons 65 years of age or older who were at increased
      risk for death or functional decline within 2 years. We included (1) a
      comprehensive measure (% of quality indicators satisfied) of quality of medical
      and geriatric care that accounted for patient preference and appropriateness in
      light of limited life expectancy and advanced dementia, and (2) a measure of
      multimorbidity, either as a simple count of conditions or as a combination of
      specific conditions. RESULTS: : Multimorbidity was associated with greater
      overall quality scores: mean proportion of quality indicators satisfied increased
      from 47% for elders with none of the prespecified conditions to 59% for those
      with 5 or 6 conditions (P < 0.0001), after controlling for number of office
      visits. Patients with greater multimorbidity also received care that was better
      than would be expected based on the specific set of quality indicators they
      triggered. CONCLUSIONS: Among older persons at increased risk of death or
      functional decline, multimorbidity results in better, rather than worse, quality
      of care.

PMID- 17515775
TI  - Combining multiple indicators of clinical quality: an evaluation of different
      analytic approaches.
AB  - OBJECTIVE: To compare different methods of combining quality indicators scores to
      produce composite scores that summarize the overall performance of health care
      providers. METHODS: Five methods for computing a composite quality score were
      compared: the "All-or-None," the "70% Standard," the "Overall Percentage," the
      "Indicator Average," and the "Patient Average." The first 2 "criterion
      referenced" methods assess the degree to which a provider has reached a threshold
      for quality of care for each patient (100% or 70%). The remaining "absolute
      score" methods produce scores representing the proportion of required care
      successfully provided. Each method was applied to 2 quality indicator datasets,
      derived from audits of UK family practitioner records. Dataset A included quality
      indicator data for 1178 patients from 16 family practices covering 23 acute,
      chronic, and preventative conditions. Dataset B included data on 3285 patients
      from 60 family practices, covering 3 chronic conditions. RESULTS: The results
      varied considerably depending on the method of aggregation used, resulting in
      substantial differences in how providers scored. The results also varied
      considerably for the 2 datasets. There was more agreement between methods for
      dataset B, but for dataset A 6 of the 16 practices moved between the top and
      bottom quartiles depending upon the method used. CONCLUSIONS: Different methods
      of computing composite quality scores can lead to different conclusions being
      drawn about both relative and absolute quality among health care providers.
      Different methods are suited to different types of application. The main
      advantages and disadvantages of each method are described and discussed.

PMID- 17515776
TI  - A refill adherence algorithm for multiple short intervals to estimate refill
      compliance (ReComp).
AB  - BACKGROUND: There are many measures of refill adherence available, but few have
      been designed or validated for use with repeated measures designs and short
      observation periods. OBJECTIVE: To design a refill-based adherence algorithm
      suitable for short observation periods, and compare it to 2 reference measures.
      METHODS: A single composite algorithm incorporating information on both
      medication gaps and oversupply was created. Electronic Veterans Affairs pharmacy
      data, clinical data, and laboratory data from routine clinical care were used to
      compare the new measure, ReComp, with standard reference measures of medication
      gaps (MEDOUT) and adherence or oversupply (MEDSUM) in 3 different repeated
      measures medication adherence-response analyses. These analyses examined the
      change in low density lipoprotein (LDL) with simvastatin use, blood pressure with
      antihypertensive use, and heart rate with beta-blocker use for 30- and 90-day
      intervals. Measures were compared by regression based correlations (R2 values)
      and graphical comparisons of average medication adherence-response curves.
      RESULTS: In each analysis, ReComp yielded a significantly higher R2 value and
      more expected adherence-response curve regardless of the length of the
      observation interval. For the 30-day intervals, the highest correlations were
      observed in the LDL-simvastatin analysis (ReComp R2 = 0.231; [95% CI, 0.222
      0.239]; MEDSUM R2 = 0.054; [95% CI, 0.049-0.059]; MEDOUT R2 = 0.053; [95% CI,
      0.048-0.058]). CONCLUSIONS: ReComp is better suited to shorter observation
      intervals with repeated measures than previously used measures.

PMID- 17515777
TI  - Induction of labor in the absence of standard medical indications: incidence and
      correlates.
AB  - BACKGROUND: Induction of labor is an increasingly common obstetrical procedure,
      with approximately 20-34% of women undergoing labor induction in the United
      States annually. OBJECTIVE: To determine the extent of labor induction in the
      absence of standard medical indications and to assess possible associations with
      maternal and infant characteristics and hospital factors. METHODS: We ascertained
      induction of labor and associated details as part of a medical record validation
      study of 4541 women with live, singleton births in 2000 in Washington State using
      medical record, birth certificate, and hospital discharge data. In this analysis,
      we report findings for the 1473 women (33% of original cohort) whose medical
      records indicated that their labors were induced. RESULTS: Among women with
      induced labor, 7.9% had no clinical information providing an indication for the
      induction, and 6.4% had only "nonstandard" indications recorded. Compared with
      women delivering in moderate volume hospitals, women who delivered at lower
      volume (odds ratios [OR] 3.9; 95% confidence intervals [CI] 1.8-8.6) or higher
      volume hospitals (OR 4.2; 95% CI 2.4-7.2) had significantly increased risk for
      undocumented indication of labor. Women who had undocumented indication for
      induction were at significantly decreased risk of giving birth at a teaching
      hospital and a public nonfederally owned hospital, and were at greater risk to
      give birth at a private religious hospital. Factors that remained independently
      associated with nonstandard indication for induction of labor were primiparas (OR
      2.4; 95% CI 1.3-4.2); multiparas (OR 4.3; 95% CI 2.5-7.4), pregnancy-induced
      hypertension (OR 0.2; 95% CI 0.1-0.4), hospital volume >or=2000 births annually
      (OR 19.9; 95% CI 6.7-58.6), primary (OR 11.7; 95% CI 4.1-33.6), and tertiary
      level hospital (OR 0.4; 95% CI 0.2-0.7). CONCLUSIONS: Our findings suggest that
      nearly 15% of inductions either were not clinically indicated according to
      standard protocols or indications were incompletely documented. At minimum,
      further studies are needed to explore how best to improve documentation of
      indications of labor because accurately describing, among other things, the
      process of labor induction, is a basic benchmark of care.

PMID- 17515778
TI  - Predictors of voluntary disenrollment from Medicare managed care.
AB  - BACKGROUND: Prior research on selection bias in Medicare plans has demonstrated
      favorable enrollment of healthier beneficiaries, resulting in plan overpayment.
      However, total selection bias depends not only on who enrolls, but also on who
      disenrolls. Few studies examine selectivity in disenrollment; it is unclear how
      those who leave plans differ from those who remain. OBJECTIVE: The examination of
      health status and plan characteristics as potential predictors of voluntary
      disenrollment from Medicare managed care. RESEARCH DESIGN: Baseline data on
      health of Medicare managed care enrollees are from the 1998 Medicare Health
      Outcomes Survey, merged with data on enrollment status and plan characteristics.
      Beneficiary voluntary disenrollment, versus continuous enrollment, 24 months
      after completing the survey was modeled as a function of perceived health in 1998
      and plan characteristics. The sample included 109,882 community-dwelling elderly.
      RESULTS: Between 1998 and 2000, 24% of Medicare managed care enrollees
      voluntarily disenrolled from plans. Poor perceived physical and mental health
      significantly increased the odds of voluntary disenrollment. Odds of
      disenrollment were higher for members of plans that increased premiums and had
      low market share between 1998 and 2000. Conversely, gaining drug coverage in a
      plan between 1998 and 2000 lowered the odds of disenrollment (relative to no
      coverage). CONCLUSION: Medicare plans experience favorable selection bias partly
      because sicker members are likelier to disenroll. Plan-level policies that
      influence market share and benefits, particularly pharmaceutical coverage, also
      have important effects on disenrollment, regardless of health effects.
      Understanding both individual and plan influences on disenrollment is critical to
      benefit coverage and disenrollment restriction ("lock in") policies.

PMID- 17515779
TI  - Health beliefs, disease severity, and patient adherence: a meta-analysis.
AB  - BACKGROUND: A large body of empirical data exists on the prediction of patient
      adherence from subjective and objective assessments of health status and disease
      severity. This work can be summarized with meta-analysis. OBJECTIVES: Retrieval
      and summary analysis of r effect sizes and moderators of the relationship between
      patient adherence and patients': (1) beliefs in disease threat; (2) rated health
      status (by physician, self, or parent); and (3) objective disease severity.
      METHODS: Comprehensive search of published literature (1948-2005) yielding 116
      articles, with 143 separate effect sizes. Calculation of robust, generalizable
      random effects model statistics, and detailed examination of study diversity with
      moderator analyses. RESULTS: Adherence is significantly positively correlated
      with patients' beliefs in the severity of the disease to be prevented or treated
      ("disease threat"). Better patient adherence is associated with objectively
      poorer health only for patients experiencing disease conditions lower in
      seriousness (according to the Seriousness of Illness Rating Scale). Among
      conditions higher in seriousness, worse adherence is associated with objectively
      poorer health. Similar patterns exist when health status is rated by patients
      themselves, and by parents in pediatric samples. CONCLUSIONS: Results suggest
      that the objective severity of patients' disease conditions, and their awareness
      of this severity, can predict their adherence. Patients who are most severely ill
      with serious diseases may be at greatest risk for nonadherence to treatment.
      Findings can contribute to greater provider awareness of the potential for
      patient nonadherence, and to better targeting of health messages and treatment
      advice by providers.

PMID- 17515780
TI  - Linking the US transplant registry to administrative claims data: expanding the
      potential of transplant research.
AB  - OBJECTIVE: In the United States, data on transplanted and waitlisted patients
      collected by the Organ Procurement and Transplantation Network (OPTN) have been
      widely used in transplantation research. Administrative claims data, collected by
      health plans for reimbursement purposes, are also commonly used in health
      services research. This study linked OPTN and private payer claims data to assess
      the relationship between data elements common to both sources. METHODS: All
      transplanted or waitlisted patients in the registry were considered for
      inclusion. A multistep match algorithm was employed to link OPTN and payer data
      from years 1995 to 2004. Variables common to both datasets that contained
      relevant information for similar time periods were compared. RESULTS: A total of
      21,419 solid organ transplant recipients and 8808 waitlist patients were included
      in the final linked database. Organ type and demographic variable distributions
      in the linked dataset were similar to the overall OPTN database. Using claims as
      the reference group, sensitivity and specificity values were on average 0.72 and
      0.69, respectively, and were highest for the indicators of immunosuppression use
      at discharge and follow-up. CONCLUSION: This comparison of payer data with
      information reported by transplant centers to the OPTN provides important insight
      into the value of both data sources. Using administrative claims to augment the
      registry data with utilization and cost information will be useful for evaluation
      of both economic and clinical endpoints in solid organ transplantation.

PMID- 17515781
TI  - Development and validation of measures to assess prevention and control of AMR in
      hospitals.
AB  - BACKGROUND: The rapid spread of antimicrobial resistance (AMR) in the US
      hospitals poses serious quality and safety problems. Expert panels, identifying
      strategies for optimizing antibiotic use and preventing AMR spread, have
      recommended hospitals undertake efforts to implement specific evidence-based
      practices. OBJECTIVE: To develop and validate a measurement scale for assessing
      hospitals' efforts to implement recommended AMR prevention and control measures.
      STUDY DESIGN: Surveys were mailed to infection control professionals in a
      national sample of 670 US hospitals stratified by geographic region, bedsize,
      teaching status, and VA affiliation. SUBJECTS: : Four hundred forty-eight
      infection control professionals participated (67% response rate). METHODS: Survey
      items measured implementation of guideline recommendations, practices for AMR
      monitoring and feedback, AMR-related outcomes (methicillin-resistant
      Staphylococcus aureus prevalence and outbreaks [MRSA]), and organizational
      features. "Derivation" and "validation" samples were randomly selected.
      Exploratory factor analysis was performed to identify factors underlying AMR
      prevention and control efforts. Multiple methods were used for validation.
      RESULTS: We identified 4 empirically distinct factors in AMR prevention and
      control: (1) practices for antimicrobial prescription/use, (2)
      information/resources for AMR control, (3) practices for isolating infected
      patients, and (4) organizational support for infection control policies. The
      Prevention and Control of Antimicrobial Resistance scale was reliable and had
      content and construct validity. MRSA prevalence was significantly lower in
      hospitals with higher resource/information availability and broader
      organizational support. CONCLUSIONS: The Prevention and Control of Antimicrobial
      Resistance scale offers a simple yet discriminating assessment of AMR prevention
      and control efforts. Use should complement assessment methods based exclusively
      on AMR outcomes.

PMID- 17515782
TI  - Factors that affect adherence to bipolar disorder treatments: a stated-preference
      approach.
AB  - BACKGROUND: Medication nonadherence is high among patients with bipolar disorder,
      and may lead to poor clinical outcomes, decreased quality of life, and increased
      resource utilization. OBJECTIVE: To investigate the factors associated with
      nonadherence and to assess the effect of patient-stated preferences on stated
      adherence to hypothetical medications. RESEARCH DESIGN: A choice-format stated
      preference Web survey was administered. In each choice question, patients were
      asked to choose among 2 or 3 different hypothetical medications. Each choice
      question was followed by a question asking patients about their likely adherence
      to the selected medication alternative. SUBJECTS: Patients (N = 469) with self
      reported bipolar disorder completed the survey which was programmed and
      administered to members of a chronic-illness Web panel. MEASURES: Factors
      associated with stated adherence to current treatment were identified. The
      effects of socioeconomic characteristics and medication attributes on stated
      adherence to hypothetical medications were assessed. RESULTS: Patient
      socioeconomic characteristics affect patients' adherence. Being white and having
      more education has a significant positive effect on adherence. Self-reported
      current adherence is a strong factor in predicting adherence for better
      medications. Medication outcome attributes, especially severity of depressive
      episodes, strongly influence patients' stated adherence to treatment. Weight gain
      and cognitive effects of a medication most significantly affected patients'
      likely adherence to medications for bipolar disorder. CONCLUSIONS: Patients are
      the final health care decision makers; their satisfaction with a medication is
      likely to affect whether or not they adhere to the medication prescribed by their
      physician. In the case of bipolar disorder, this study suggests patients are
      likely to be more adherent to medications that reduce the severity of depressive
      episodes and do not cause weight gain or cognitive side effects. By understanding
      the factors that improve adherence, health care providers can optimize
      prescribing patterns, which may ultimately lead to more effective management and
      improvement in the patient's condition.

PMID- 17515783
TI  - Team structure and adverse events in home health care.
AB  - OBJECTIVE: To identify relationships between variations in team structure and
      risk-adjusted adverse events across 86 teams in a large US home health care
      organization. METHODS: Patient episode data were collected for two 6-month
      periods, January-June 2002 (N = 54,732 episodes) and January-June 2003 (N =
      51,560 episodes). An adverse event was defined as having 1 or more events defined
      by the Centers for Medicare and Medicaid Services for home health care episodes.
      Events were risk adjusted using 2 alternative approaches-a Z-score and a Fixed
      Effects (FE)-score, for each team in each period. These scores (1 for each team
      in each period) were then regressed against objective measures of team structure.
      RESULTS: The regressions based on the FE-score as the measure of quality
      performed better than the traditional Z-score. Based on these regressions we find
      that volume (number of episodes) (P = 0.03), number of weekend visits (P = 0.02),
      and workload distribution (P = 0.02) were negatively associated with the
      occurrence of adverse events, whereas higher weekend admissions (P = 0.01) were
      positively associated with adverse events. CONCLUSIONS: Our analysis identifies a
      number of key team-level organizational variables that influence adverse events
      in home health care services. We also have demonstrated that the FE-score is a
      more accurate measure of team quality, as opposed to the Z-score, given that it
      focuses only on "team attributable" adverse events by isolating and excluding
      random variation from the quality score.

PMID- 17515784
TI  - Potentially avoidable hospitalizations for COPD and pneumonia: the role of
      physician and practice characteristics.
AB  - BACKGROUND: Hospitalizations for bacterial pneumonia and chronic obstructive
      pulmonary disease (COPD) occur frequently, but many are potentially avoidable.
      OBJECTIVE: To examine associations between elderly patients' usual physician and
      practice characteristics, and the risk of hospitalization for bacterial pneumonia
      and COPD. RESEARCH DESIGN: Time-to-event analysis of Medicare claims from 2000
      (baseline year) through 2001-2002 (follow-up years) for beneficiaries whose usual
      physician participated in the 2000-2001 Community Tracking Study Physician
      Survey. SUBJECTS: A total of 509,613 patients and 5764 physicians for pneumonia
      hospitalizations; subset of 91,318 beneficiaries with an antecedent diagnosis of
      COPD and 5074 physicians for COPD hospitalizations. MEASURES: Hospitalizations
      for bacterial pneumonia or COPD occurring in 2001-2002. RESULTS: Beneficiaries
      whose usual physician had been in practice for >10 years (vs. <or=10 years) were
      at lower risk for both pneumonia (AHR [adjusted hazard ratio] 0.88, 95% CL
      [confidence limits] 0.82-0.94, and COPD hospitalization (AHR 0.87, 95% CL 0.80
      0.96). Risk of hospitalization for COPD was lower among beneficiaries whose usual
      physician reported that clinical practice guidelines had an important effect,
      compared with those reporting relatively little impact, on their clinical
      practice (AHR 0.88, 95% CL 0.80-0.96). Patients had higher risk of both types of
      hospitalizations if their physician's practice had >5% Medicaid revenue (vs. 0
      5%, P < 0.0001), or reported more (vs. less) difficulty securing ancillary
      services (P < 0.01 for bacterial pneumonia and P = 0.05 for COPD). Patient
      socioeconomic status, previous respiratory hospitalizations, and comorbidities
      had the strongest associations with hospitalization. CONCLUSIONS: Given that
      physicians who report limited access to ancillary services and high Medicaid case
      volume have patients who experience higher rates of admission for COPD and
      pneumonia, additional resources and quality improvement interventions targeting
      these providers should be priorities.

PMID- 17515785
TI  - Nurse working conditions and patient safety outcomes.
AB  - BACKGROUND: System approaches, such as improving working conditions, have been
      advocated to improve patient safety. However, the independent effect of many
      working condition variables on patient outcomes is unknown. OBJECTIVE: To examine
      effects of a comprehensive set of working conditions on elderly patient safety
      outcomes in intensive care units. DESIGN: Observational study, with patient
      outcome data collected using the National Nosocomial Infection Surveillance
      system protocols and Medicare files. Several measures of health status and fixed
      setting characteristics were used to capture distinct dimensions of patient
      severity of illness and risk for disease. Working condition variables included
      organizational climate measured by nurse survey; objective measures of staffing,
      overtime, and wages (derived from payroll data); and hospital profitability and
      magnet accreditation. SETTING AND PATIENTS: The sample comprised 15,846 patients
      in 51 adult intensive care units in 31 hospitals depending on the outcome
      analyzed; 1095 nurses were surveyed. MAIN OUTCOME MEASURES: Central line
      associated bloodstream infections (CLBSI), ventilator-associated pneumonia,
      catheter-associated urinary tract infections, 30-day mortality, and decubiti.
      RESULTS: Units with higher staffing had lower incidence of CLBSI, ventilator
      associated pneumonia, 30-day mortality, and decubiti (P <or= 0.05). Increased
      overtime was associated with higher rates of catheter-associated urinary tract
      infections and decubiti, but slightly lower rates of CLBSI (P <or= 0.05). The
      effects of organizational climate and profitability were not consistent.
      CONCLUSIONS: Nurse working conditions were associated with all outcomes measured.
      Improving working conditions will most likely promote patient safety. Future
      researchers and policymakers should consider a broad set of working condition
      variables.

PMID- 17515786
TI  - Quality of care in hospitals with a high percent of Medicaid patients.
AB  - BACKGROUND: Certain hospitals play a central role in ensuring Medicaid-insured
      patients' access to care. Their quality of care is critical to evaluate.
      OBJECTIVE: To determine whether hospitals for which Medicaid patients represent a
      high percentage of total discharges provide a different quality of care than
      other hospitals. RESEARCH DESIGN: Cross-sectional analysis. SUBJECTS: Acute care
      hospitals participating in the first Hospital Compare public report (released
      November 2004) and the 2004 American Hospital Association hospital survey.
      MEASURES: Hospitals serving 1 standard deviation above the national mean
      percentage of Medicaid patients were designated high Medicaid hospitals.
      Performance was assessed using percent compliance with 10 processes of care for 3
      conditions: myocardial infarction, congestive heart failure, and community
      acquired pneumonia. RESULTS: Among the 2874 nonteaching hospitals, high Medicaid
      hospitals had lower adherence (P < 0.01) than other nonteaching hospitals on all
      10 indicators. Of particular clinical importance, high Medicaid nonteaching
      hospitals less frequently prescribed beta-blockers (83% vs. 90%%, P < 0.0001) and
      aspirin at discharge in myocardial infarction (85% vs. 91%%, P < 0.0001), and
      administered antibiotics on time in CAP (68% vs. 75%, P < 0.0001). Among teaching
      institutions, there were few differences between high Medicaid and other
      hospitals. CONCLUSIONS: Among hospitals publicly reporting on the Hospital
      Compare Web site, nonteaching hospitals treating a high percentage of Medicaid
      patients had lower adherence to quality indicators than other nonteaching
      hospitals on 10 indicators. Further research is needed to determine what factors
      contribute to differences in reported quality.

PMID- 17515787
TI  - Hair cell differentiation becomes tissue specific by E9.5 in mouse inner ear.
AB  - Tissue culture is a standard method to study tissue interactions during
      embryogenesis. The serum that is usually used in culture can, however, confound
      results as it includes unidentified factors. In this study, we used a serum-free
      otocyst culture to investigate the tissue interactions that determine hair cell
      fate in mice otocysts. Otocysts cultured with surrounding tissues have the
      ability to produce mature hair cells in serum-free otocyst culture. Although
      isolated otocysts from E9.5 mice produced hair cells, those from E9.0 mice could
      not. This indicates that the mouse otocyst gains the ability to generate hair
      cells between E9.0 and E9.5 and that this ability depends on signals from the
      surrounding mesenchyme and/or the hindbrain.

PMID- 17515788
TI  - Brain area, age and viral vector-specific glial cell-line-derived neurotrophic
      factor expression and transport in rat.
AB  - We investigated the feasibility of viral vector-mediated expression and axonal
      transport of the glial cell-line-derived neurotrophic factor, a potential
      antiepileptic agent, to the hippocampus and the piriform cortex, areas involved
      in the induction and spread of seizure activity. Glial cell-line-derived
      neurotrophic factor overexpression was induced by injections of recombinant
      vectors derived from serotype 2 adeno-associated virus or lentivirus. We found
      that recombinant adeno-associated viral vector was able to effectively transduce
      mitral cells of the olfactory bulb and pyramidal cells of CA1, resulting in
      transport of glial cell-line-derived neurotrophic factor to the piriform cortex
      and to the contralateral CA1 area, respectively. These data suggest that the
      recombinant adeno-associated viral vector vector system is an optimal alternative
      for therapeutic glial cell-line-derived neurotrophic factor gene transduction and
      transport of the protein to the epileptogenic brain areas.

PMID- 17515789
TI  - Generation of cells committed towards the photoreceptor fate for retinal
      transplantation.
AB  - Cell transplantation is an active field of research to replace lost cells in
      retinal dystrophies to potentially restore visual function. We hypothesized that
      in-vitro differentiated retinal stem cells would integrate the appropriate
      retinal layer and differentiate into photoreceptors when transplanted during
      development. Here we show that retinal stem cells driven to the photoreceptor
      fate start to incorporate the retina and express photoreceptor markers but do not
      survive. Nevertheless surviving grafted cells express the glial marker glial
      fibrillary acidic protein and incorporate the ganglion cell layer as well as the
      inner plexiform layer. These results suggest that the maturation state of the
      photoreceptors is primordial to obtain robust incorporation and that a fine
      tuning of retinal stem cells differentiation should provide adequate cells for
      transplantation.

PMID- 17515790
TI  - Cortical categorization failure in 2-month-old infants at risk for dyslexia.
AB  - Cortical auditory categorization was assessed in 2-month-old infants at genetic
      risk for dyslexia and controls. Manipulated /bAk/ and /dAk/ speech stimuli were
      used as frequently presented standards. The neuroelectric brain responses of the
      control infants were highly sensitive to the phoneme boundary that separated
      these stimuli, but the infants at risk showed no signs of cortical categorical
      perception. Cortical sources of the responses were predominantly found in the
      left hemisphere for the control infants, but mainly in the right hemisphere for
      the infants at risk. The results demonstrate that impaired categorical perception
      in dyslexia is already present in infants at risk for the disorder.

PMID- 17515791
TI  - Cyclosporine affects the proliferation and differentiation of neural stem cells
      in culture.
AB  - Cyclosporine is one of the foremost immunosuppressive agents for cell, tissue,
      and organ transplantation. Cyclosporine is, however, associated with significant
      side effects in the host, and may also affect the fate of the donor cells. This
      study was performed to test whether cyclosporine may change the fate of neural
      stem cells, as neural stem cell transplant has become a potential treatment for
      neurological disorders and damage. Results of this study showed that cyclosporine
      inhibited the proliferation significantly in a dosage-dependent manner.
      Cyclosporine also affected the differentiation of neural stem cells, which mainly
      increased astrocyte genesis and decreased neuron differentiation.

PMID- 17515792
TI  - Immunocytochemical localization of ubiquitin A-52 protein in the mouse inner ear.
AB  - The ubiquitin A-52 residue ribosomal protein fusion product 1 (UbA52) is a gene
      highly expressed specifically in the inner ear. Through cellular localization we
      immunocytochemically investigated its function in the inner ear. In the adult
      mouse, UbA52 protein was distributed in the strial marginal cells and vestibular
      dark cells, which regulate the endolymphatic ion homeostasis. In the developing
      mouse cochlea, no significant staining was observed from birth to postnatal day
      3, whereas after postnatal day 6, strong UbA52-immunoreactivities were observed
      in strial marginal cells. Endolymphatic K concentration is elevated between
      postnatal days 3-8: therefore, our results indicate that UbA52 may have a
      functional role in regulation of ion secretion in the inner ear.

PMID- 17515793
TI  - Brain development in Chinese children and adolescents: a structural MRI study.
AB  - This is the first systematic study of Chinese children's brain development. Using
      optimized voxel-based morphometry, we investigated age-related changes in gray
      and white matter in Chinese children and adolescents aged 7 to 23 years. Results
      showed mostly linear reductions, but also some linear increases, in gray matter
      in many regions of the brain. Gray matter changes were more evident in the
      parietal and temporal regions than in the frontal and occipital regions. White
      matter showed significant linear increases in internal capsule, arcuate
      fasciculus, superior and inferior longitudinal fasciculus, and cingulate
      fasciculus.

PMID- 17515794
TI  - The event-related potential effects of cognitive conflict in a Chinese character
      generation task.
AB  - High-density event-related potentials were recorded to examine the
      electrophysiologic correlates of the evaluation of possible answers provided
      during a Chinese character-generation task. We examined three conditions: the
      character given was what participants initially generated (Consistent answer),
      the character given was correct (Unexpected Correct answer), or it was incorrect
      (Unexpected Incorrect answer). Results showed that Unexpected Correct and
      Incorrect answers elicited a more negative event-related potential deflection
      (N320) than did Consistent answers between 300 and 400 ms. Dipole source analysis
      of difference waves (Unexpected Correct or Incorrect minus Consistent answers)
      localized the generator of the N320 in the anterior cingulate cortex. The N320
      therefore likely reflects the cognitive change or conflict between old and new
      ways of thinking while identifying and judging characters.

PMID- 17515795
TI  - Sex differences in spinal excitability during observation of bipedal locomotion.
AB  - This study investigated whether there are sex differences in the spinal
      excitability of the human mirror-neuron system. We measured the modulation of
      spinal excitability, elicited by Hoffmann reflex in the left plantar flexor
      muscle (soleus), when women and men participants observed videos of bipedal heel
      stepping (plantar dorsiflexion), standing still, and bipedal toe-stepping
      (plantar flexion). Men and women were similarly divided in their sex judgments of
      the observed legs. Our results indicate that whereas both men and women mimicked
      spinal excitability to the observed bipedal step, only women participants
      produced stronger modulation of spinal excitability. These findings demonstrate
      that the human mirror-neuron system exhibits sex differences in spinal
      excitability.

PMID- 17515796
TI  - Late response evoked by cerebellar stimuli: effect of optokinetic stimulation.
AB  - We previously demonstrated that late electromyographic responses with a latency
      of 100 ms were evoked bilaterally in soleus muscles following transcranial
      magnetic stimulation over the left cerebellum. Efferent fibers from the left
      cerebellum modulate vestibulospinal tract influences on the extensor muscles of
      the left hindlimb. Here, we investigated whether the vestibulospinal tract
      mediates this late response. We activated the vestibulospinal tract by
      optokinetic stimulation. Our results show that the latency of the soleus
      electromyographic response is shortened by optokinetic stimulation, but the
      latency of the motor response evoked by the corticospinal tract is unchanged.
      These findings support our hypothesis that vestibulospinal tracts mediate late
      electromyographic responses, and allow the development of techniques to assess
      the human vestibulospinal system function.

PMID- 17515797
TI  - Early response of neural stem/progenitor cells after X-ray irradiation in vitro.
AB  - We investigated the effect of oxidative stress on cell cycle regulation of neural
      stem/progenitor cells in neurosphere culture. We exposed murine neural
      stem/progenitor cells to 2 Gy of X-ray irradiation at 48 h after first passage.
      We found that G2 and G1-arrested cells increased at 3 and 12 h after X-ray
      irradiation, respectively by using laser scanning cytometer. We revealed that
      such G2 and G1 arrests were correlated with phosphorylation of cdc2 and p53,
      respectively by Western blotting analysis. Furthermore, we found that the effects
      of X-ray irradiation of neural stem/progenitor cells involved inactivation of
      Notch signal. These results suggest that the drastic response of neural
      stem/progenitor cells after X-ray irradiation occurred even in the short period.

PMID- 17515798
TI  - Mismatch negativity reflects sensory and phonetic speech processing.
AB  - We examined phonetic and sensory processes in speech perception using mismatch
      negativity, an event-related potential component congruent with discrimination,
      but which occurs for unattended stimuli. Adult listeners (N=16) heard a repeated
      standard (the syllable 'da') that was interrupted infrequently by a phonetically
      different 'deviant' syllable ('ba'). The acoustic difference between standard and
      deviant was manipulated to create both acoustically Strong and Weak deviant
      stimuli. Mismatch negativities in response to the Strong deviant were
      significantly greater than those for the Weak deviant, in spite of the fact that
      both represented stable instances of the phonetic category. The data suggest that
      the mismatch negativity component can be strongly influenced by sensory factors
      beyond what is predicted by overt categorization and discrimination judgments.

PMID- 17515799
TI  - Cutaneous mechanoreceptors contribute to the generation of a cortical reflex in
      speech.
AB  - Owing to the lack of muscle spindles and tendon organs in the perioral system,
      cutaneous receptors may contribute to speech sensorimotor processes. We have
      investigated this possibility in the context of upper lip reflexes, which we have
      induced by unexpectedly stretching the facial skin lateral to the oral angle.
      Skin stretch at this location resulted in long latency reflex responses that were
      similar to the cortical reflexes observed previously. This location reliably
      elicited the reflex response, whereas the skin above the oral angle and the skin
      on the cheek did not. The data suggest that cutaneous mechanoreceptors are
      narrowly tuned to deformation of the facial skin and provide kinesthetic
      information for rapid sensorimotor processing in speech.

PMID- 17515800
TI  - Phonological deficit in school children is reflected in the Mismatch Negativity.
AB  - Deficits in processing of auditory stimuli are known to play an important role in
      the aetiology of dyslexia. To specify the auditory deficit in children at risk
      for dyslexia, 19 children with a phonological deficit and 15 controls were tested
      using the mismatch negativity event-related potential, which reflects
      preattentive auditory processing. Children with a phonological deficit, not yet
      suffering from dyslexia, had similar mismatch negativity patterns to dyslexics.
      The deficit was speech specific, because there were significant group differences
      only with syllables but not with pure tones.

PMID- 17515801
TI  - Visual vector inversion in the posterior parietal cortex.
AB  - In the antisaccade task, a saccade must be triggered towards the mirror location
      of a visual target. The neural basis required for this visual vector inversion
      remains unclear, although neuronal activities reflecting this process have been
      recorded in the monkey lateral intraparietal area. We examined a patient with a
      small, right-sided, posterior parietal stroke who complained of difficulty in
      manipulating visual information. Antisaccades were markedly hypometric rightwards
      but normal leftwards. Largely unaffected performances in other saccade tasks
      revealed that visual and motor processing were not significantly affected.
      Antisaccade inaccuracy could therefore be ascribed to the impairment of visual
      vector inversion, a processing specifically required in this task. These findings
      provide the first evidence in humans that visual vector inversion could be an
      intrinsic property of the posterior parietal cortex.

PMID- 17515802
TI  - Coffee drinking enhances the analgesic effect of cigarette smoking.
AB  - Nicotine (from cigarette smoke) and caffeine (from coffee) have analgesic effects
      in humans and experimental animals. We investigated the combined effects of
      coffee drinking and cigarette smoking on pain experience in a group of moderate
      nicotine-dependent, coffee drinking, young smokers. Pain threshold and pain
      tolerance were measured during cold pressor test following the habitual nocturnal
      deprivation of smoking and coffee drinking. Smoking increased pain threshold and
      pain tolerance in both men and women. Coffee drinking, at a dose that had no
      independent effect, doubled the increase in pain threshold induced by smoking.
      The effect could not be explained by a cumulative raise in blood pressure. Our
      data suggest that caffeine enhances the analgesic effect of nicotine.

PMID- 17515803
TI  - Effects of tobacco and cigarette smoke extracts on serotonergic raphe neurons in
      the rat.
AB  - Tobacco components other than nicotine might participate in the behavioural
      effects of smoking. In this study, in-vivo recordings of serotonergic dorsal
      raphe neurons were performed in the anesthetized rat, whereas tobacco extracts,
      cigarette smoke extracts, nicotine, nornicotine or anabasine were intravenously
      injected. All substances inhibited the neurons, and all inhibitions were
      completely blocked by the nicotine receptor antagonist mecamylamine. The effects
      of the extracts were much more potent than those of individual substances. These
      results support the hypothesis that the acute inhibition of serotonin neurons by
      tobacco compounds is completely related to an effect on nicotine receptors.
      Tobacco extracts and tobacco smoke extracts may be useful tools for the study of
      the effects of central effects of smoking.

PMID- 17515804
TI  - Inverted event-related potentials response to illusory contour in boys with
      autism.
AB  - We examined the hypothesis of lower-level processing abnormalities related to
      perceptual grouping in boys with autism aged 3-6 years. We investigated event
      related potentials response to visual elements that either formed perceptually
      coherent illusory contour or were arranged in a noncoherent way. The results
      showed that in healthy boys the illusory contour as compared with control
      stimulus elicited enhanced negativity of N1 peak (C effect), which has been
      previously found in adults. Autistic boys demonstrated the reliable inverted
      illusory contour effect, that is, more positive N1 amplitude to illusory contour.
      We hypothesized that boys with autism were sensitive to difference between
      illusory contour and control figures basing on collinearity processing mechanisms
      implemented in neural circuitry of primary visual cortex.

PMID- 17515805
TI  - Fibroblast growth factor 20 gene and Parkinson's disease in the Japanese
      population.
AB  - A genetic association between the fibroblast growth factor 20 (FGF20) gene and
      Parkinson's disease has been found by the pedigree disequilibrium test. This
      association, however, was not replicated by a case-control association study. In
      order to clarify the association between the FGF20 gene and Parkinson's disease,
      we attempted to replicate this association by a case-control association study
      using a large number of Japanese samples (1388 patients and 1891 controls).
      rs1721100 exhibited a significant difference in allele C versus G (P=0.0089), and
      in genotype CC+CG versus GG (P=0.0053). Haplotype association analysis showed
      that haplotype 2 was the protective haplotype for Parkinson's disease
      (permutation-P=0.0075). These results suggest that the FGF20 gene is a
      susceptibility gene for Parkinson's disease in the Japanese population.

PMID- 17515806
TI  - Attentional orienting to graspable objects: what triggers the response?
AB  - We used event-related potentials to determine whether attentional orienting to
      graspable objects depends on the type of motor representation they implicitly
      activate - object and/or hand specific. Our paradigm was based on varying the
      visual hemifield location (left vs. right) of a task-irrelevant 'tool'. As our
      left-handed participants had object and hand-specific motor representations
      lateralized to their left and right cerebral hemispheres, respectively, the motor
      representation activated on each trial thus varied with the tool's hemifield. In
      question was whether attentional orienting would also vary with the tool's
      hemifield. Our ERP data, however, indicated that attention was drawn to the
      tool's location regardless of hemifield, suggesting that graspable objects can
      trigger attentional orienting via either an object or hand-specific motor
      representation.

PMID- 17515807
TI  - An event-related potential study on perceptual learning in grating orientation
      discrimination.
AB  - This study aims to investigate the neural mechanism of visual perceptual learning
      in grating orientation discrimination. We recorded event-related potentials of
      human adults when they were trained with a grating orientation discrimination
      task. Although psychophysical thresholds decreased significantly across training
      sessions, event-related potentials showed larger P2 and P3 amplitudes and smaller
      N1 amplitudes over the parietal/occipital areas with more practice. In line with
      the psychophysical thresholds, the training effect on the P2 and P3 were specific
      to stimulus orientation. The N1 effect, however, was generalized over differently
      oriented gratings. Our findings show that several stages of visual processing are
      involved in perceptual learning and provide an illustration of the temporal
      relationship between specific and generalized perceptual learning in human
      adults.

PMID- 17515808
TI  - The position of the aorta relative to the spine in patients with left thoracic
      scoliosis: a comparison with normal patients.
AB  - STUDY DESIGN: Analysis axial magnetic resonance images (MRIs) identifying the
      position of the aorta in left thoracic scoliosis and normal patients. OBJECTIVES:
      To determine the position of the aorta in patients with left thoracic scoliosis
      and to compare these findings with those seen in normal patients. SUMMARY OF
      BACKGROUND DATA: Screws placed during an anterior spinal fusion and
      instrumentation for right thoracic scoliosis are in proximity to the aorta, which
      is primarily due to the position of the aorta on the posterolateral left aspect
      of the vertebra. There are no studies that have evaluated the aorta in left
      thoracic scoliosis. METHODS: A retrospective review of all patients with an MRI
      with left thoracic scoliosis (Group LTS) was performed and compared with patients
      with a normal straight spine (Group N). Axial MRI images from T4 to L3 in both
      groups were analyzed to include the aorta-vertebral angle (AVA), where 0 degrees
      = aorta directly lateral to the left and 180 degrees = directly lateral to the
      right. RESULTS: There were 20 patients in Group LTS and 43 patients in Group N.
      There were no differences in age (13.1 vs. 14.0 years) or gender (52% vs. 62%
      females) between the LTS and N groups. The aorta was positioned more anterior
      (larger AVA) to the vertebral body at levels T4 thru T11 (average, 70.1 degrees
      vs. 40.6 degrees) and L3 (77.1 degrees vs. 70.9 degrees) in Group LTS compared
      with group N (P < 0.05). With increasing thoracic coronal Cobb angle, the aorta
      was positioned more laterally to the right (larger AVA) at T8 and T10 (P < 0.05).
      In the LTS group, curves greater than 40 degrees had a larger AVA (91.4 degrees
      vs. 57.7 degrees) at apical levels (T7-T10) than for curves < or =40 degrees (P <
      0.05). CONCLUSIONS: In left thoracic LTS, the aorta is positioned more anteriorly
      and to the right (toward the concavity) compared with patients with a straight
      spine. This position will allow full access to the convexity of the left curve to
      perform an anterior fusion/release as well as instrumentation and is not in the
      trajectory of a well-placed anterior screw. This relative safety was not seen at
      the apex of larger curves (>40 degrees).

PMID- 17515809
TI  - Pyogenic intradural abscess: a case report.
AB  - STUDY DESIGN: A case report of pyogenic intradural abscess is described.
      OBJECTIVES: The rarity of the presentation and its successful management are
      discussed. SUMMARY OF BACKGROUND DATA: Intradural abscesses are exceptionally
      rare. METHOD: The abscess was drained by performing a posterior midline lumbar
      durotomy, and intravenous antibiotics were initiated. RESULT: At the 1 year
      follow-up, the patient has made significant neurologic recovery. CONCLUSION:
      Intradural pyogenic abscess secondary to chronic pyogenic spondylodiscitis is a
      rare manifestation. MRI is a vital component in diagnosis, which revealed key
      pathologic features within the dural sac as well as in the vertebral column. An
      emergency decompression and appropriate antibiotic regimen is the solution for a
      favorable outcome.

PMID- 17515810
TI  - Combined extraforaminal and intradiscal cement leakage following percutaneous
      vertebroplasty.
AB  - STUDY DESIGN: A case report and review of the literature are presented.
      OBJECTIVE: To describe an extremely rare case of combined extraforaminal and
      intradiscal cement leakage in different vertebral levels following percutaneous
      vertebroplasty. SUMMARY OF BACKGROUND DATA: Cement leaks in vertebroplasty are
      relatively common but generally not clinically significant. To our knowledge,
      this is the first report of extraforaminal cement leakage inducing radiculopathy
      combined with intradiscal cement leakage evoking acute adjacent compression
      fracture. METHODS: A 78-year-old woman with L2 and L5 osteoporotic compression
      fractures received vertebroplasty. Two weeks after surgery, the patient presented
      severe low back pain radiating to the right thigh, with associated weakness and
      numbness in the right thigh and lower leg. Roentgenographic images revealed
      cement leakage into the right extraforamen of L2-L3 as well as leakage into L4-L5
      disc with acute adjacent compression fracture of L4. RESULTS: Surgical
      intervention was required to relieve discomfort. One-stage posterior approach was
      performed: right L2-L3 intertransverse process approach with removal of
      extraforaminal leaked cement and posterior instrumentation from L3-L5 and
      posterior fusion. The severe low back pain, leg pain, and neurologic deficit
      associated weakness all improved after surgery. CONCLUSION: Although considered a
      minimally invasive procedure, percutaneous vertebroplasty with
      polymethylmethacrylate is not risk free. Intractable neurologic complications can
      occur if it is not performed by experienced physicians under appropriate
      indications and cautionary safeguards.

PMID- 17515812
TI  - The position of the aorta relative to the spine: is it mobile or not?
AB  - STUDY DESIGN: This study analyzes the mobility of the aorta relative to the spine
      in patients with a herniated thoracic disc requiring surgical intervention.
      OBJECTIVES: To determine the mobility of the aorta relative to the spine with the
      patient in prone and supine position. SUMMARY OF BACKGROUND DATA: In anterior
      scoliosis surgery, safe screw placement is important and knowledge of the
      position of the aorta relative to the spine is crucial. To the authors'
      knowledge, there are no studies on the mobility of the aorta relative to the
      spine with the patient in different positions. METHODS: All 50 patients before
      surgery had a computed tomography (CT) and/or magnetic resonance (MR) scans of
      the involved spinal segment in supine position, as well as a CT with intrathecal
      contrast in prone position. The aorta-vertebral angle and the aorta-vertebral
      distance were measured on as many levels as possible. RESULTS: In supine
      position, the aorta is positioned left lateral to the vertebral body at
      midthoracic levels (T4-T8) and more anterior to the vertebral body at lower
      thoracic levels (T9-L2). In prone position, the aorta moves to a more
      anteromedial position relative to the vertebra, which is most significant at
      levels T4 to T8. The mediolateral aorta-vertebral distance according to Sevastik
      is shorter in prone position, whereas the anterior-posterior distance according
      to Sucato is larger, especially at levels T5 to T10. CONCLUSIONS: We demonstrate
      a substantial difference in the position of the aorta relative to the spine in
      prone and in supine position, which is most markedly seen at levels T4 to T8. The
      aorta is positioned posterolateral to the spine in supine position and more
      anteromedial in prone position. Before performing anterior thoracolumbar spine
      surgery, we suggest to measure vertebral body width, as well as the position of
      the aorta in the prone and in the supine patient to decide if his approach is
      technically feasible, or if an alternative (contralateral) approach is
      preferable.

PMID- 17515813
TI  - Increase of 200-kDa neurofilament-immunoreactive afferents in the substantia
      gelatinosa in allodynic rats induced by compression of the dorsal root ganglion.
AB  - STUDY DESIGN: An experimental study on mechanical allodynia, c-Fos expression,
      and 200-kDa-neurofilament immunoreactive (IR) afferent expression in the
      substantia gelatinosa related to compression of dorsal root ganglion (DRG).
      OBJECTIVES: To evaluate the presence of allodynia in DRG compression model and to
      demonstrate that the structural changes of spinal dorsal horn related to DRG
      compression. SUMMARY OF BACKGROUND DATA: A previous experimental report has
      demonstrated that the peripheral nerve injury may trigger some structural changes
      of the superficial spinal dorsal horn. These changes of the spinal dorsal horn
      were thought to be important for the modulation of pain sensations such as
      allodynia. METHODS: Sixty-eight male rats were used. The left L5 lamina was
      exposed and a drill hole was made in it. A stainless rod was placed close to the
      left L5 DRG through the drill hole. Behavioral testing with von Frey filament was
      performed. On day 28 after surgery, c-Fos expression in the spinal dorsal horn by
      non-noxious stimulation was examined. L5 spinal cord and bilateral L5 DRG
      specimens were stained with antibody for 200-kDa neurofilament (RT97). In
      addition, 2 or 3 spinal cord sections per rats were processed for immunoelectron
      microscopy. RESULTS: In the DRG compression group, the mechanical withdrawal
      threshold was decreased, c-Fos expression by non-noxious stimulation was observed
      in the spinal dorsal horn, and there were many RT97-IR afferents in the
      superficial spinal dorsal horn. Immunoelectron microscopic observations showed
      that RT97-IR terminals made synaptic contact with neurons in the superficial
      spinal dorsal horn. There were no significant differences in the distribution of
      RT97-IR neurons in DRG between compression and sham group. CONCLUSIONS: DRG
      compression induced allodynia and that RT97-IR afferents increased in the
      superficial dorsal horn of the spinal cord. The increase of RT97-IR afferents may
      be related to the mechanisms for the observed allodynia.

PMID- 17515814
TI  - BDNF, NT-3, and NGF released from transplanted neural progenitor cells promote
      corticospinal axon growth in organotypic cocultures.
AB  - STUDY DESIGN: Experimental study of spinal cord injury using an organotypic slice
      culture. OBJECTIVE: To clarify the mechanism of corticospinal axon regeneration
      following transplantation of neural progenitor cells (NPCs) in the injured spinal
      cord. SUMMARY OF BACKGROUND DATA: Several mechanisms underlying central nervous
      system regeneration after transplantation of NPCs have been proposed; however,
      the precise mechanism has not been clarified. Previously, we demonstrated that
      transplanted NPCs secreted humoral factors that in turn promoted corticospinal
      axon growth using the unique organotypic coculture system involving brain cortex
      and spinal cord from neonatal rats. METHODS: Cultured NPCs were immunostained
      with antibodies against neurotrophic factors including brain-derived neurotrophic
      factor (BDNF), neurotrophin (NT)-3, nerve growth factor (NGF), and ciliary
      neurotrophic factor (CNTF) both before and after differentiation. To evaluate
      corticospinal axon growth quantitatively, we used the organotypic coculture
      system. The dissected brain cortex and spinal cord obtained from neonatal rats
      were aligned next to each other and cultured on a membrane. NPCs were
      transplanted onto the cocultures. Furthermore, neutralizing antibodies against
      BDNF, NT-3, NGF, or CNTF were added to the cocultures. Axon growth from the brain
      cortex into the spinal cord was assessed quantitatively using anterograde axon
      tracing with DiI. RESULTS: The cultured NPCs were positively immunostained by
      antibodies against BDNF, NT3, NGF, and CTNF both before and after
      differentiation. Transplantation of NPCs promoted axon growth from the brain
      cortex into the spinal cord. The axon growth promoted by NPCs was significantly
      suppressed by the addition of neutralizing antibodies against BDNF, NT-3, and NGF
      but not CNTF. CONCLUSION: The neurotrophic factors, BDNF, NT-3, and NGF, secreted
      by transplanted NPCs, were involved in the promotion of corticospinal axon growth
      after transplantation of NPCs.

PMID- 17515815
TI  - Association of gene polymorphisms with intervertebral disc degeneration and
      vertebral osteophyte formation.
AB  - STUDY DESIGN: Cross-sectional cohort study of elderly people. OBJECTIVES: To
      examine the factors influencing osteophyte formation without lumbar disc
      degeneration and to estimate the implications of osteophytes from the viewpoint
      of low back pain and gene polymorphisms. SUMMARY OF BACKGROUND DATA: The
      degenerative changes that occur in the intervertebral discs are the point of
      departure of osteophyte formation. Several studies on factors associated with
      genetic susceptibility to spinal osteophyte formation, such as VDR and TGF-beta1.
      However, there are no detailed studies concerning osteophytes not accompanied
      with disc degeneration. METHODS: A total of 387 elderly persons were recruited,
      and disc degeneration and osteophyte formation were evaluated. The cases with
      osteophyte formation were classified into 3 groups: osteophyte formation with
      disc height narrowing (n = 217), osteophyte formation without disc height
      narrowing (n = 99), and control group defined as the cases without osteophyte
      formation (n = 71). Twelve genotypes were characterized. Correlations between
      these degenerative factors and the polymorphisms were analyzed. RESULTS: The
      prevalence of low back pain was significantly greater in the group of osteophyte
      formation with disc height narrowing than the other 2 groups. In the polymorphism
      of alcohol dehydrogenase (ADH2), prevalence of osteophyte formation without disc
      height narrowing was less in His/Arg (odds ratio = 0.57, P = 0.041) and Arg/Arg
      (odds ratio = 0.41, P = 0.18) than His/His. CONCLUSIONS: Patients with osteophyte
      formation preceding intervertebral disc narrowing had a lower risk of low back
      pain compared with those without osteophytes. The 47Arg polymorphism in the ADH2
      may act to suppress osteophyte formation unaffected by disc degeneration.

PMID- 17515816
TI  - Cell polarity in the anulus of the human intervertebral disc: morphologic,
      immunocytochemical, and molecular evidence.
AB  - STUDY DESIGN: Human intervertebral disc tissue was obtained in a prospective
      study of cell morphology and gene expression. Experimental studies were approved
      by the authors' Human Subjects Institutional Review Board. Discs were obtained
      from surgical specimens or control donors. OBJECTIVES: To determine if there is
      morphologic and molecular evidence for polarity in cells of the human anulus.
      SUMMARY OF BACKGROUND DATA: In many tissues, cells become polarized as they
      develop functional specializations, which involve cell-cell and cell
      extracellular matrix interactions and polarized targeting mechanisms. The highly
      specialized lamellar organization of the anulus is well recognized and suggests
      that this structure may be the result of directed secretion of extracellular
      matrix components by polarized disc cells. METHODS: Human disc specimens from
      donor and surgical patients were examined with light and electron microscopy to
      assess morphology. Specimens were examined for immunocytochemical localization of
      PAR3 and claudin-1 and -11, recognized polarity proteins, and additional anulus
      specimens were examined for expression of polarity-related genes using microarray
      analysis. In vitro monolayer and 3-dimensional anulus cultures were also studied
      for gene expression, and additional surgical anulus specimens were used to obtain
      gene expression data using real time RT-PCR. RESULTS: At the ultrastructural
      level, anulus cells showed localization of secretory organelles and directed
      deposition of extracellular matrix in one portion of the cell, with the nucleus
      positioned in the opposite side of the cell. Expression of the polarity-related
      genes claudin-11 and PAR3 and PARD6 was confirmed using RT-PCR and microarray
      studies and immunocytochemical analyses. The percentage of cells positive for
      PAR3 immunolocalization was significantly greater in the outer anulus (100%) than
      in either the inner anulus (43.8%) or nucleus pulposus (22.6%). CONCLUSIONS: At
      the macroscopic level, the characteristic anular lamellar morphology implies a
      specialized architectural formation and organization, which is achieved by the
      tissue-specific function of polarized cells. Morphologic and molecular studies
      provided evidence for the presence of polarity in cells in the anulus. These
      findings advance our understanding of anulus disc cell function in production of
      highly aligned collagen fibrils and macroaggregates of these collagen fibrils
      into lamellar collagen bundles. Such disc cell activity is important in
      development and maintenance of the tissue-specific extracellular matrix of the
      disc.

PMID- 17515817
TI  - The presence of pleiotrophin in the human intervertebral disc is associated with
      increased vascularization: an immunohistologic study.
AB  - STUDY DESIGN: An immunohistological study of surgical specimens of human
      intervertebral disc. OBJECTIVE: To examine the presence of pleiotrophin in
      diseased or damaged intervertebral disc tissue and the association between its
      presence and the extent of tissue vascularization and innervation. SUMMARY OF
      BACKGROUND DATA: Increased levels of pleiotrophin, a growth and differentiation
      factor that is active in various pathophysiologic processes, including
      angiogenesis, has been associated with osteoarthritic changes of human articular
      cartilage. The association between pleiotrophin expression and pathologic
      conditions of the human intervertebral disc is unknown. METHODS: Specimens of
      human lumbar intervertebral discs, obtained following surgical discectomy, were
      divided into 3 groups: non-degenerated discs (n = 7), degenerated discs (n = 6),
      and prolapsed discs (n = 11). Serial tissue sections of each specimen were
      immunostained to determine the presence of pleiotrophin, blood vessels (CD34
      positive endothelial cells), and nerves (neurofilament 200 kDa [NF200]-positive
      nerve fibers). RESULTS: Pleiotrophin immunoreactivity was seen in disc cells,
      endothelial cells, and in the extracellular matrix in most specimens of
      intervertebral disc but was most prevalent in vascularized tissue in prolapsed
      discs. There was a significant correlation between the presence of pleiotrophin
      positive disc cells and that of CD34-positive blood vessels. NF200-positive
      nerves were seen in vascularized areas of more degenerated discs, but nerves did
      not appear to codistribute with blood vessels or pleiotrophin positivity in
      prolapsed discs. CONCLUSIONS: Pleiotrophin is present in pathologic human
      intervertebral discs, and its prevalence and distribution suggest that it may
      play a role in neovascularization of diseased or damaged disc tissue.

PMID- 17515818
TI  - Recombinant human osteogenic protein-1 upregulates proteoglycan metabolism of
      human anulus fibrosus and nucleus pulposus cells.
AB  - STUDY DESIGN: In vitro assessment of the effects of recombinant human osteogenic
      protein-1 (rhOP-1) on the proteoglycan metabolism of human intervertebral disc
      cells. OBJECTIVES: To determine whether rhOP-1 is effective in stimulating the
      cell proliferation and proteoglycan metabolism of human intervertebral disc cells
      cultured in alginate beads. SUMMARY OF THE BACKGROUND DATA: OP-1 has been shown
      to stimulate the proteoglycan and collagen synthesis of rabbit intervertebral
      disc cells in vitro. In vivo, a single injection of rhOP-1 restored the disc
      height of a degenerated disc in the rabbit anular-puncture model. The effect of
      rhOP-1 on human intervertebral disc cells remains unknown. METHODS: Human nucleus
      pulposus and anulus fibrosus cells were isolated from the discs of 4 cadaveric
      spines and one surgical specimen. After preculture for 7 days, alginate beads
      containing nucleus pulposus and anulus fibrosus cells were cultured for 21 days
      in media containing 10% fetal bovine serum with 0, 100, or 200 ng/mL rhOP-1 and
      supplements. The synthesis and accumulation of proteoglycans and the DNA content
      were biochemically assessed. RESULTS: The addition of rhOP-1 to the media
      resulted in the prevention of a decreased cell number during culture. Treatment
      with rhOP-1, compared with the control condition (10% fetal bovine serum),
      significantly upregulated proteoglycan synthesis and accumulation in alginate
      beads in all cases tested. A longer exposure over 14 days to rhOP-1 resulted in a
      pronounced response. The retention of newly-synthesized proteoglycan was higher
      in the rhOP-1-treated cells than in the control. CONCLUSIONS: rhOP-1 was
      effective in stimulating the cell proliferation and proteoglycan metabolism of
      human intervertebral disc cells in vitro. The results supported the hypothesis
      that an in vivo injection of rhOP-1 may increase the metabolic activity of disc
      cells or prevent apoptosis of disc cells in a degenerated disc. However, the
      requirement for a long exposure to rhOP-1 for human cells may suggest the need
      for a prolonged supply of rhOP-1 by a drug delivery system or by repeated
      injections.

PMID- 17515820
TI  - Multidirectional testing of one- and two-level ProDisc-L versus simulated
      fusions.
AB  - STUDY DESIGN: An in vitro human cadaveric biomechanical study. OBJECTIVES: To
      evaluate intervertebral rotation changes due to lumbar ProDisc-L compared with
      simulated fusion, using follower load and multidirectional testing. SUMMARY OF
      BACKGROUND DATA: Artificial discs, as opposed to the fusions, are thought to
      decrease the long-term accelerated degeneration at adjacent levels. A
      biomechanical assessment can be helpful, as the long-term clinical evaluation is
      impractical. METHODS: Six fresh human cadaveric lumbar specimens (T12-S1)
      underwent multidirectional testing in flexion-extension, bilateral lateral
      bending, and bilateral torsion using the Hybrid test method. First, intact
      specimen total range of rotation (T12-S1) was determined. Second, using pure
      moments again, this range of rotation was achieved in each of the 5 constructs:
      A) ProDisc-L at L5-S1; B) fusion at L5-S1; C) ProDisc-L at L4-L5 and fusion at L5
      S1; D) ProDisc-L at L4-L5 and L5-S1; and E) 2-level fusion at L4-L5 to L5-S1.
      Significant changes in the intervertebral rotations due to each construct were
      determined at the operated and nonoperated levels using repeated measures single
      factor ANOVA and Bonferroni statistical tests (P < 0.05). Adjacent-level effects
      (ALEs) were defined as the percentage changes in intervertebral rotations at the
      nonoperated levels due to the constructs. RESULTS: One- and 2-level ProDisc-L
      constructs showed only small ALE in any of the 3 rotations. In contrast, 1- and 2
      level fusions showed increased ALE in all 3 directions (average, 7.8% and 35.3%,
      respectively, for 1 and 2 levels). In the disc plus fusion combination (construct
      C), the ALEs were similar to the 1-level fusion alone. CONCLUSIONS: In general,
      ProDisc-L preserved physiologic motions at all spinal levels, while the fusion
      simulations resulted in significant ALE.

PMID- 17515821
TI  - Preliminary study on biomechanics of vertebroplasty: a computational fluid
      dynamics and solid mechanics combined approach.
AB  - STUDY DESIGN: Algorithm development for the automatic finite element modeling of
      patient vertebra. OBJECTIVE: To present a technique for automatic generation of
      patient specific computational fluid dynamics (CFD) models for intraosseous PMMA
      cement flow simulation. The secondary objective is to demonstrate the possibility
      of using resultant PMMA cement distribution for post-PVP stress-strain analyses.
      SUMMARY OF BACKGROUND DATA: There are no noninvasive methods for the
      visualization of PMMA cement flow. In addition, optimum volume and distribution
      of PMMA cement are still not known. Computational models that allow patient
      specific intraosseous PMMA cement flow visualization as well as
      postvertebroplasty mechanical evaluation would be advantageous. METHODS: We
      developed an algorithm coded into a custom platform that inputs patient CT
      datasets. Hounsfield unit values were used to assign permeability values as well
      as modulus to the finite element model before analyses. Several user inputs are
      required, and these reflect the decisions made by physicians that practice
      vertebroplasty. As a case study, we isolated a single L1 vertebra from patient CT
      dataset and used our platform for model generation. Simulated vertebroplasty was
      performed for different PMMA cement volumes and at different placements to study
      the effects of varying distribution. RESULTS: Increased needle injection pressure
      was observed as the volume of PMMA increases and as the distribution of PMMA is
      in close proximity to the cortical walls. Stiffness of augmented vertebral body
      also increases with increased volume of PMMA administered. Varying distributions,
      for the same volume, of PMMA cement did not alter stiffness drastically.
      CONCLUSION: Our custom platform and technique for modeling vertebral bodies may
      contribute significantly to the science of vertebroplasty. Intraosseous PMMA
      cement flow can be visualized before vertebroplasty, and needle position altered
      for optimization. Also, parametric computational studies on the
      postvertebroplasty biomechanical effects of vertebroplasty are now enhanced with
      such a modeling capability.

PMID- 17515822
TI  - Influence of pain distribution on gait characteristics in patients with low back
      pain: part 1: vertical ground reaction force.
AB  - STUDY DESIGN: In a cross-sectional study, vertical ground reaction force (GRF)
      during 2 speeds of walking were compared between 3 age- and sex-matched groups:
      back pain only (BPO) group, back pain with referred leg pain (LGP) group, and a
      control group. OBJECTIVE: The purpose was to evaluate the influence of pain
      distribution on vertical GRF of patients with low back problems during 2 walking
      speed conditions: preferred and fastest speeds. SUMMARY OF BACKGROUND DATA:
      People with low back pain often have difficulty walking. A better understanding
      of how pain distribution differentially affects walking will facilitate
      clinicians' assessment and enhance treatment in patients with low back pain
      problems. METHODS: All participants walked on a 7.62-m walkway. Vertical GRF
      parameters were recorded during stance phase using a force platform for each
      walking speed condition. Multivariate analysis of covariance was used for
      statistical analysis, with gait velocity as the covariate. RESULTS: The BPO and
      control groups did not differ significantly in vertical GRF during both walking
      speed conditions (P > or = 0.11). All vertical GRF parameters of the LGP group,
      except the peak loading force (P = 0.374), were significantly less than those of
      the control group during preferred walking speed condition (P < or = 0.008).
      However, there was no significant difference in the vertical GRF components
      between LGP and control groups during the fastest walking speed condition (P > or
      = 0.07). CONCLUSIONS: Pain distribution of people with low back problems
      differentially influences the vertical GRF they experience during walking. When
      walking at preferred speed, those with referred leg pain seem to use additional
      strategies besides walking slowly to attenuate the amount of force imposed on
      their painful leg. When challenged to walk at their fastest speed, people with
      back pain only walk as fast and withstand comparable amount of force as their
      pain-free counterparts.

PMID- 17515823
TI  - Superiority of multilevel cervical arthroplasty outcomes versus single-level
      outcomes: 229 consecutive PCM prostheses.
AB  - STUDY DESIGN/SETTING: Class 2 level of evidence: This is a prospective,
      consecutive series of 229 prosthetic implantations that were concurrently
      enrolled between single-level versus multilevel cervical arthroplasty comprising
      an FDA Pilot Study. OBJECTIVE: This study investigated multilevel cervical disc
      replacement in relation to single-level cervical arthroplasty to find if the same
      reduction in clinical success would occur with this alternative treatment.
      SUMMARY OF BACKGROUND DATA: Usually, the clinical outcomes of instrumented
      cervical fusions deteriorate as the number of vertebral levels of involvement
      increases. METHODS: A total of 229 patients presented with cervical herniated
      nucleus pulposus, cervical spondylosis, and/or adjacent segment disease with
      cervical radiculopathy or myelopathy. Following anterior cervical neurologic
      decompression seventy-one patients required porous coated motion (PCM) cervical
      arthroplasties from C3-C4 to C7-T1 (Group S, single level). Sixty-nine patients
      underwent 158 multilevel PCM cervical arthroplasties (Group M, multilevel) during
      the same time interval, for the same indications, performed by the same surgeons
      under the same clinical protocol: double level, 53 cases; three levels, 12 cases:
      and 4 levels, 4 cases. RESULTS: The self-assessment outcomes instruments showed
      significantly more improvement for the multilevel cases. The mean improvement in
      the NDI for the single cases was 37.6% versus the multilevel cases mean
      improvement in NDI was 52.6% (P = 0.021). The difference between the two was
      statistically significant. The mean improvement in the VAS showed the same
      association: single-level mean improvement 58.4% versus the multilevel cases mean
      VAS improvement was 65.9%. The Odom's were also more improved for the multilevel
      versus the single-level group: 93.9% versus 90.5% in the excellent, good, and
      fair categories. The reoperation rates and serious adverse events were similar
      between the single-level (S = 3) to the multilevel arthroplasty (M = 2) groups.
      Kaplan-Meier implant survivorship analysis at 3 years for the cohort of 229
      prostheses was 94.5% (confidence interval, 1.00-0.820). CONCLUSIONS: This
      prospective study of cervical arthroplasty is the first report to date showing
      significantly improved clinical outcomes for multilevel cervical arthroplasty
      compared with single-level cervical disc replacement using an FDA validated
      outcome instrument.

PMID- 17515824
TI  - One-year results of X Stop interspinous implant for the treatment of lumbar
      spinal stenosis.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVE: To prospectively assess
      the clinical outcome of patients with symptomatic lumbar spinal stenosis before
      and at periodic intervals after X Stop implantation and to compare the data with
      previous studies. SUMMARY OF BACKGROUND DATA: The X Stop Interspinous Process
      Distraction Device is a relatively new interspinous implant designed for patients
      with symptomatic spinal stenosis particularly neurogenic claudication.
      Previously, a randomized study has shown a 75% improvement in symptoms and
      physical function at 1-year post-X Stop implantation for lumbar spinal stenosis.
      The only other study is a preliminary report of only 10 patients with variable
      intervals of clinical outcome assessment. METHOD: Forty consecutive patients were
      enrolled and surgically treated with X Stop implantation. The X Stop device was
      implanted at the stenotic segment, which was either at 1 or 2 levels in each
      patient. They were clinically evaluated at the preoperative, 3-month, 6-month,
      and 1-year stage with clinical questionnaires (Zurich Claudication Questionnaire,
      Oswestry Disability Index, and SF-36). RESULTS: Sixteen patients failed to
      complete all the questionnaires at all time intervals and hence were excluded,
      leaving 24 patients who had completed all questionnaire at all time interval. By
      12 months, 54% of these 24 patients reported clinically significant improvement
      in their symptoms, 33% reported clinically significant improvement in physical
      function, and 71% expressed satisfaction with the procedure. 29% of the patients
      required caudal epidural after 12 months after surgery for recurrence of their
      symptoms of neurogenic claudication. CONCLUSION: The results of this prospective
      observational study indicate that X Stop offers significant short-term
      improvement over a 1-year period. It is a safe, effective, and less invasive
      alternative for treatment of lumbar spinal stenosis. Our results, however, are
      less favorable than the previous multicenter, randomized study.

PMID- 17515825
TI  - Patient characteristics at the initial visit to a scoliosis clinic: a cross
      sectional study in a community without school screening.
AB  - STUDY DESIGN: A cross-sectional study was conducted of all patients referred for
      an initial visit to the orthopedic outpatient clinic of a metropolitan pediatric
      hospital in Canada for suspected adolescent idiopathic scoliosis (AIS).
      OBJECTIVE: To document the appropriateness of current referral patterns for AIS
      in comparison to those that were prevailing before discontinuation of school
      screening in Canada. SUMMARY OF BACKGROUND DATA: The consequences of the
      discontinuation of school scoliosis screening programs on the referral patterns
      of AIS patients remain unknown. METHODS: The clinical and radiologic charts of
      the 636 consecutive patients referred for scoliosis evaluation over a 1-year
      period were reviewed. Patients were classified according to defined criteria of
      appropriateness of referral based on skeletal maturity and curve magnitude.
      RESULTS: Of the 489 suspected cases of AIS, 206 (42%) had no significant
      deformity (Cobb angle <10 degrees ) and could be considered as inappropriate
      referrals. In subjects with confirmed AIS, 91 patients (32%) were classified as
      late referrals with regards to brace treatment indications. CONCLUSIONS: These
      findings suggest that current referral mechanisms for AIS are leading to a
      suboptimal case-mix in orthopedics in terms of appropriateness of referral.

PMID- 17515826
TI  - Analysis of sagittal alignment in thoracic and thoracolumbar curves in adolescent
      idiopathic scoliosis: how do these two curve types differ?
AB  - STUDY DESIGN: Retrospective chart review and radiographic analysis. OBJECTIVE: To
      determine if differences exist in the sagittal alignment of adolescent idiopathic
      scoliosis (AIS) patients with thoracic versus thoracolumbar curve patterns.
      SUMMARY OF BACKGROUND DATA: Relative anterior overgrowth has been suggested as
      the possible pathomechanism behind thoracic scoliosis. Given the proposed
      importance of the sagittal alignment on the development of AIS and the known
      association between pelvic parameters and sagittal alignment, the authors
      postulate that pelvic incidence may influence the location of vertebral column
      collapse associated with different AIS curve types. METHODS: A multicenter
      surgical database was used to compare preoperative radiographic measurements
      between patients with primary thoracic curves (Lenke 1A, B), primary
      thoracolumbar curves (Lenke 5), and normal adolescents. RESULTS: Pelvic incidence
      was significantly greater in both groups of AIS patients compared with normal
      adolescents. Patients in the primary thoracic curve group were found to have a
      significantly increased sacral slope and a decreased thoracic kyphosis relative
      to the control group. Patients in the primary thoracolumbar curve group had a
      significantly increased pelvic tilt; however, a relatively normal thoracic
      kyphosis, lumbar lordosis, and sacral slope compared with the respective control
      values. CONCLUSION: An increased pelvic incidence, associated with both thoracic
      and thoracolumbar curves when compared with the normal adolescent population,
      does not appear to be the potential determinant of the development of thoracic
      versus thoracolumbar scoliosis, but may be a risk factor for the development of
      adolescent idiopathic scoliosis. The theory of anterior overgrowth may be
      supported by the identification of thoracic hypokyphosis, despite an increased
      pelvic incidence and lumbar lordosis, in patients with thoracic scoliosis. The
      association between sagittal measurements and the etiology of thoracolumbar curve
      formation is less clear; however, regional anterior overgrowth in the lumbar
      spine may also be responsible for the deformity.

PMID- 17515827
TI  - Sex differences in consequences of musculoskeletal pain.
AB  - STUDY DESIGN: Cross-sectional population-based study. OBJECTIVE: To study sex
      differences in consequences of musculoskeletal pain (MP): limited functioning,
      work leave or disability, and healthcare use. SUMMARY OF BACKGROUND DATA: MP is a
      major public health problem in developed countries due to high prevalence rates
      and considerable consequences. There are indications that consequences of MP
      differ for men and women. METHODS: Data of a Dutch population-based study were
      used, limited to persons 25 to 64 years of age (n = 2517). Data were collected by
      a postal questionnaire. RESULTS: Women with any MP report more healthcare use for
      MP, i.e., contact with a medical caregiver and use of medicines than men, while
      men report more work disability (ever in life) due to low back pain only,
      irrespective of work status. None of the sex differences can be explained by age,
      household composition, educational level, smoking status, overweight, physical
      activity, and pain catastrophizing. Older age was related to more limited
      functioning due to MP (women), work disability due to MP (men), and healthcare
      use due to MP (men and women). A one-person household was associated with work
      disability (women) and use of medicines (men). Low educational level was
      associated with limited functioning (men), work leave (men), contact with a
      medical caregiver (men), and work disability (men and women). Smoking was
      associated with limited functioning (men), work leave (women), and healthcare use
      (women). Physical inactivity was associated with limited functioning due to MP in
      women. Pain catastrophizing was associated with limited functioning, work leave,
      and healthcare use (men and women) and work disability (men). CONCLUSIONS:
      Consequences of MP show a slightly different pattern for men and women. Women
      with any MPreport more healthcare use for MP, while men report more work
      disability due to low back pain only. These sex differences can not be explained
      by general risk factors, but associations between these factors and consequences
      of MP show some sex differences.

PMID- 17515828
TI  - Lamotrigine is neuroprotective in the energy deficiency model of MPTP intoxicated
      mice.
AB  - The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibits the
      mitochondrial complex I of the respiratory chain. This results in ATP and ion
      homeostasis disturbances, which lead to selective death of the substantia nigra
      dopaminergic neurons. Well known as a Parkinson's disease model, the MPTP animal
      model also provides a potential paradigm of the energy deficiencies found in
      childhood. In these conditions, anticonvulsants may provide neuroprotection by
      limiting cellular energy consumption. We tested valproate, topiramate and
      lamotrigine in the MPTP mouse model. Dopamine transporter (DAT) density was
      assessed by quantitative autoradiography, tyrosine hydroxylase (TH) was evaluated
      by immunohistochemistry and dopamine (DA) levels by HPLC-ED whereas neuronal
      apoptosis was monitored through active caspase-3. Expectedly, the DAT density, TH
      immunoreactive neurons and DA content in the MPTP group were respectively reduced
      to 51%, 40% and 26% versus control animals. Unlike valproate and topiramate,
      lamotrigine provided a significant neuroprotection against MPTP in maintaining
      these levels at 99%, 74% and 58% respectively and reducing the induced apoptosis.
      Altogether, the data indicate that lamotrigine limits dopaminergic neuronal death
      in the substantia nigra and promotes striatal dendrites sprouting. Lamotrigine, a
      widely used and well-tolerated molecule in young patients, could represent a
      valuable adjuvant therapy in various energy deficiency conditions during
      childhood.

PMID- 17515829
TI  - Atypical measles and enhanced respiratory syncytial virus disease (ERD) made
      simple.
AB  - Atypical measles and enhanced respiratory syncytial virus disease (ERD) were
      serious diseases that resulted from exposure of children immunized with
      inactivated vaccines against measles virus (MV) and respiratory syncytial virus
      (RSV) to the respective wild-type agents in the 1960s. Although the clinical
      manifestations of both illnesses were different, the immune responses elicited
      and primed for by the vaccines shared important similarities. Both vaccines
      failed to elicit long-lived protective antibody and to promote cytotoxic T
      lymphocyte responses. In both cases, postvaccination exposure to wild type virus
      during community outbreaks was associated with immune complex deposition in
      affected tissues, vigorous CD4 T lymphocyte proliferative responses, and a Th2
      bias of the immune response. No relapses of atypical measles or ERD were ever
      reported. In this manuscript, the pathogeneses of both enhanced diseases and the
      requirements for the generation of protective antibodies against MV and RSV are
      discussed, to contribute to the development of newer safe and effective vaccines
      against these important pathogens.

PMID- 17515830
TI  - Differential expression of matrix metalloproteinases and inhibitors in developing
      rat lung mesenchymal and epithelial cells.
AB  - Lung development requires extracellular matrix remodeling. This involves matrix
      metalloproteinases (MMPs) and their endogenous inhibitors [tissue inhibitors of
      metalloproteinases (TIMPs)]. Because these have been generally studied only in
      whole lung, we focused specifically on mesenchymal and epithelial cells freshly
      isolated at various developmental stages. In fibroblasts, the most striking
      developmental change was a peak (fourfold the prenatal level) of membrane type 1
      (MT1)-MMP transcript during alveolarization, consistent with the known crucial
      role of MT1-MMP in this process. TIMP-1 and -2 mRNAs transiently increased on
      postnatal d (pn) 3. In alveolar epithelial cells (AECs), MMP-2 expression was
      maximal on fetal d (f) 19 when alveolar type II cells (ATII) differentiate and on
      pn5; by contrast, MT1-MMP expression changed little and TIMP-1 expression
      decreased with advancing gestation. In cells expressing in vitro the ATI
      phenotype, TIMP-1 and -2 activities were nine- and fivefold those in cells
      expressing ATII features, respectively, whereas ATII presented higher MMP-2
      activity and were the only cell type to express MMP-9. This indicates higher
      remodeling potential for ATII. Pulmonary mesenchymal and epithelial cells have
      therefore quite distinct MMP/TIMP expression patterns. Changes in cell
      compartments should be specifically documented in developing lung diseases such
      as bronchopulmonary dysplasia in which changes in MMP activities have been
      reported.

PMID- 17515831
TI  - Maternal and intra-amniotic corticosteroid effects on lung morphometry in preterm
      lambs.
AB  - We investigated the effects of intra-amniotic (IA) betamethasone or budesonide
      injections on lung structure 2 or 7 d after treatment in preterm fetal sheep.
      Pregnant ewes received intra-amniotic betamethasone (2 mg/kg fetal weight),
      budesonide (2 mg/kg), saline or maternal intramuscular betamethasone (0.5 mg/kg
      maternal weight), or saline. Lambs were delivered 2 or 7 d later at 124 d of
      gestation. Morphometric analysis was conducted on the right upper lung lobe.
      Intra-amniotic corticosteroids, 2 or 7 d before delivery, resulted in higher
      average alveolar volumes than controls (2 d: 25%-35%, 7d: 15%-25%). All
      corticosteroid treatments resulted in thinning of alveolar walls 7 d after
      treatment and a higher proportion of alveolar ducts and a lower alveolar wall
      fraction relative to controls 2 or 7 d after treatment. The changes in structural
      lung indices correlated with the improved lung function at 2 d. Structural lung
      indices and increased surfactant correlated with the improved lung function at 7
      d. Similar structural changes induced by intra-amniotic corticosteroids and
      maternal intramuscular betamethasone were associated with improvements in lung
      function at 2 and 7 d.

PMID- 17515832
TI  - Elevated carbohydrate-deficient transferrin (CDT) and its normalization on
      dietary treatment as a useful biochemical test for hereditary fructose
      intolerance and galactosemia.
AB  - Abnormalities in protein glycosylation are reported in fructosemia (HFI) and
      galactosemia, although, particularly in HFI, the published data are limited to
      single cases. The purpose was to investigate the usefulness of the carbohydrate
      deficient transferrin (CDT) profile for identification and monitoring of these
      disorders. First we analyzed CDT values before and shortly after the diagnosis in
      10 cases of HFI and 17 cases of galactosemia. In all patients, elevated CDT
      levels were found that significantly (p < 0.0001) decreased with the therapeutic
      diet (27.3 +/- 11.5% versus 9.3 +/- 5.1% for HFI and 43.8 +/- 14.1% versus 11.2
      +/- 4.0% for galactosemia). To evaluate the use of CDT test in monitoring
      compliance, the test was performed in 25 HFI patients on fructose-restricted
      diet. We found an elevated CDT level on 104 from 134 tests (mean 11.3 +/- 5.5%,
      control 1.5%-6.2%). The fructose intake was found to be 90 +/- 70 mg/kg/d, and
      the diet was unbalanced. A number of patients presented lower height, elevated
      urinary uric acid excretion, and hypercalciuria. In conclusion, abnormal
      percentage of CDT (%CDT) values may allow prompt detection of HFI (or
      galactosemia). Persistence of some abnormalities in HFI on treatment may be
      caused by trace amounts of fructose ingestion and/or a deficient diet. Regular
      %CDT measurements are suggested for HFI treatment monitoring.

PMID- 17515833
TI  - Angiotensin II type 2 receptor gene polymorphism in Caucasian children with a
      wide spectrum of congenital anomalies of the kidney and urinary tract.
AB  - The A-1332G transition of the angiotensin II type 2 receptor (AT2R) gene was
      found to occur more often in males with ureteropelvic (UPJO) or ureterovesical
      junction obstruction (UVJO). However, other studies have shown controversial
      results. Tauhe frequency of this polymorphism was investigated in 275 Caucasian
      children (153 boys, 122 girls) with a wide spectrum of congenital anomalies both
      of upper (165) and lower (110) urinary tract system and in 200 controls (100
      boys, 100 girls). Among the included malformations, renal agenesis and duplex
      collecting system (DCS) were studied for the first time. The frequency of the G
      allele did not differ among patients (193 of 397 total alleles, 48.6%) and
      controls (146 of 300, 48.7%). No significant difference was also found in the
      frequency of the G allele in subgroups of congenital uropathies compared with
      controls. When analysis was performed in males and females separately, no
      significant difference was found in the frequency of the G allele in male (45.1%)
      or female (50.8%) patients compared with male (57.0%) or female (44.5%) controls.
      Our data indicate that the AT2R gene A-1332G transition is not associated with
      the development of human congenital uropathies and further investigations should
      be carried out to unravel their etiology.

PMID- 17515834
TI  - Blood gases and pulmonary blood flow during resuscitation of very preterm lambs
      treated with antenatal betamethasone and/or Curosurf: effect of positive end
      expiratory pressure.
AB  - Resuscitation of very premature lambs with positive end-expiratory pressure
      (PEEP) improves oxygenation and reduces pulmonary blood flow (PBF). However, the
      effects of PEEP on blood gases and PBF have not been studied in preterm lambs
      receiving antenatal corticosteroids or postnatal surfactant. Lambs were delivered
      at 125 d of gestation (term 147 d) and ventilated with a tidal volume (VT) of 5
      mL/kg using different levels of PEEP. Four treatment groups were studied: (1)
      antenatal betamethasone 24 and 36 h before delivery; (2) postnatal Curosurf; (3)
      antenatal betamethasone and postnatal Curosurf; (4) untreated controls. Blood
      gases, PBF, and ventilator parameters were recorded during the first 2 h.
      Increasing PEEP improved oxygenation even after antenatal betamethasone and
      postnatal Curosurf, without adverse effects on arterial PCO2. Increasing PEEP
      reduced PBF; this effect was not altered by betamethasone and/or Curosurf. In
      very preterm lambs ventilated with fixed VT, increasing levels of PEEP improved
      oxygenation after antenatal glucocorticoids and/or postnatal surfactant. These
      treatments do not alter the deleterious effects of high levels of PEEP on PBF.

PMID- 17515835
TI  - Effect of vernix caseosa on the penetration of chymotryptic enzyme: potential
      role in epidermal barrier development.
AB  - The fetal epidermal barrier undergoes rapid development during late gestation
      despite conditions injurious to the skin postnatally, i.e. prolonged exposure to
      water (urine) and noxious substances such as pancreatic chymotrypsin.
      Nevertheless, at birth, term newborns have a superb epidermal barrier.
      Concomitant with formation of the stratum corneum in utero, vernix caseosa forms
      a natural multifunctional cream separating the skin surface from the amniotic
      fluid with possible unique barrier properties. Therefore, we investigated the
      effect of native vernix, synthetic vernix, and Desitin on penetration of
      chymotrypsin, a proteolytic enzyme present in both developing epidermis and
      meconium. Alpha-chymotrypsin penetration through test materials was conducted in
      vitro using a modified Franz diffusion cell. The presence of alpha-chymotrypsin
      in vernix and a possible inhibitory effect of vernix on alpha-chymotrypsin
      activity were investigated. Vernix films significantly impeded chymotrypsin
      penetration compared with controls during 24-h exposure experiments. Alpha
      chymotryptic activity in vernix was undetectable, and vernix showed no endogenous
      inhibition of such activity. Both synthetic vernix and Desitin significantly
      impeded alpha-chymotrypsin penetration compared with controls during 9-h exposure
      experiments. With respect to the developing epidermal barrier, these results are
      consistent with the hypothesis that vernix films retain endogenous (epidermal)
      chymotrypsin while preventing exposure to exogenous (pancreatic) chymotrypsin.

PMID- 17515836
TI  - Peroxynitrite decomposition catalyst FeTMPyP provides partial protection against
      intestinal ischemia and reperfusion injury in infant rats.
AB  - Free radicals are important in development of intestinal ischemia-reperfusion
      (I/R) injury, leading to intestinal and pulmonary damage. We evaluated the
      effects of peroxynitrite decomposition catalyst FeTMPyP in infant intestinal I/R.
      Suckling rats underwent 40 min intestinal ischemia + 90 min reperfusion. At
      reperfusion, animals received saline or FeTMPyP. Groups were (n = 11 per group):
      1) control+saline; 2) I/R+saline; 3) I/R+FeTMPyP. Increased histologic injury and
      ICAM-1 expression were observed in ileum of both I/R+saline and I/R+FeTMPyP rats,
      but P-selectin expression was increased in I/R+saline animals only versus
      controls. Myeloperoxidase (neutrophil infiltration marker) was increased in ileum
      and lungs of I/R+saline rats, but FeTMPyP prevented this in the ileum. I/R+saline
      animals showed higher malondialdehyde (lipid peroxidation marker) in ileum and
      lungs versus both control+saline and I/R+FeTMPyP rats. Glutathione was decreased
      in all I/R animals, but oxidized and total glutathione were higher in I/R+FeTMPyP
      than the I/R+saline group. Nitrate+nitrite concentration (systemic nitric oxide
      production) was elevated in I/R+saline but not in I/R+FeTMPyP animals. FeTMPyP
      provides limited protection against intestinal I/R in neonatal rats by reducing
      ileal P-selectin expression, systemic nitric oxide production, neutrophil
      infiltration in ileum and lipid peroxidation in both lungs and ileum; and
      preserving intestinal antioxidant capacity.

PMID- 17515837
TI  - Differential effects of phenylalanine on Rac1, Cdc42, and RhoA expression and
      activity in cultured cortical neurons.
AB  - Phenylketonuria (PKU) is characterized by a high concentration of phenylalanine,
      which can lead to mental retardation. One of the characteristic pathologic
      changes in untreated phenylketonuria patients is a reduction in the number of
      axons, dendrites, and synapses in the brain. This is thought to be due to the
      toxic effects of phenylalanine and/or its metabolites, however, the underlying
      mechanism remains unclear. In this study, we observed that phenylalanine reduced
      the number of dendrites and dendritic spines in cultured neurons. We further
      demonstrated that phenylalanine down-regulated Rac1, Cdc42, and RhoA mRNA and
      protein expression. Pull-down assays indicated that phenylalanine caused a
      decrease in Rac1/Cdc42 activity but increased RhoA activity. Expression of a
      dominant negative RhoA or treatment with a Rho-associated kinase specific
      inhibitor, Y-27632, partly inhibited the phenylalanine-induced decrease in
      dendrite numbers. In conclusion, we have demonstrated that phenylalanine affects
      the expression and activity of Rac1, Cdc42, and RhoA. Furthermore, RhoA signaling
      is involved in the inhibitory effect of phenylalanine on dendritic branching.
      These results may provide an important insight into the molecular mechanism
      underlying phenylalanine-induced abnormalities of dendrites, specifically in
      phenylketonuria neuronal injury.

PMID- 17515838
TI  - Developmental cell/molecular biologic approach to the etiology and treatment of
      bronchopulmonary dysplasia.
AB  - We have taken a basic biologic approach to elucidate the pathophysiology of
      bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, based
      on cell/molecular mechanisms of physiologic lung development. Stretch coordinates
      parathyroid hormone-related protein (PTHrP) signaling between the alveolar type
      II cell and the mesoderm to coordinately up-regulate key genes for the
      homeostatic fibroblast phenotype- including peroxisome proliferator activated
      receptor gamma (PPARgamma), adipocyte differentiation related protein (ADRP), and
      leptin- and the retrograde stimulation of type II cell surfactant synthesis by
      leptin. Each of these paracrine interactions requires cell-specific receptors on
      adjacent cells derived from the mesoderm or endoderm, respectively, to serially
      up-regulate the signaling pathways between and within each cell-type. It is this
      functional compartmentation that is key to understanding how specific agonists
      and antagonists can predictably affect this mechanism of alveolar homeostasis.
      Using a wide variety of pathophysiologic insults associated with BPD- barotrauma,
      oxotrauma, and infection, we have found that there are type II cell and/or
      fibroblast cell/molecular effects generated by these insults, which can lead to
      the BPD phenotype. We have exploited these cell-specific mechanisms to
      effectively prevent and treat lung injuries using PPARgamma agonists to sustain
      this signaling pathway. It is critically important to judiciously select
      physiologically and developmentally relevant interventions when treating the
      preterm neonate.

PMID- 17515839
TI  - Prolidase isoenzymes in the rat: their organ distribution, developmental change
      and specific inhibitors.
AB  - Lack of prolidase I (PD I) leads to prolidase deficiency, a disease characterized
      by intractable skin lesions, recurrent respiratory infections, and mental
      retardation. The present study was undertaken to characterize and determine the
      physiologic roles of different prolidase isoenzymes. Two isoforms of prolidase
      were isolated from rat kidney. PD I showed higher activity against seryl-proline
      and alanyl-proline, whereas PD II was active especially against methionyl
      proline. PD I was highly concentrated in the small intestine and kidney, whereas
      PD II was shown not to vary in the organs examined. Expression of PD I and PD II
      in the small intestine were maximal within 1 wk of birth, and then rapidly
      declined. The changes of prolidase in the kidney and heart were found to differ
      slightly. N-benzyloxycarbonyl-l-proline and captopril inhibited PD I dose
      dependently, but showed no inhibition of PD II at low concentrations. NiCl2
      inhibited PD II much more effectively than PD I. Our findings suggest that PD I
      functions by way of an intestinal peptide carrier, which may also be regulated by
      the uptake of various iminodipeptides. Similarly, age-related alterations of
      prolidase isoenzymes suggest that intestinal PD II also participates in
      absorption of proline and other amino acids early in life.

PMID- 17515840
TI  - 11-Beta hydroxysteroid dehydrogenase type 2 in human adult and fetal lung and its
      regulation by sex steroids.
AB  - 11-Beta hydroxysteroid dehydrogenase type 2 (HSD2) oxidizes the biologically
      active glucocorticoid (GC), cortisol, to inactive cortisone. We characterized
      HSD2 gene expression and activity in human adult and fetal lung tissues and in
      cultured fetal lung explants, and examined the potential regulation of HSD2 in
      the fetal lung by sex steroids. Human adult lung, fetal lung, and cultured fetal
      lung explant tissues contained similar amounts of HSD2 mRNA. However, higher
      levels of HSD2 protein were detected in human fetal lung tissue than in adult
      lung, with expression being restricted to a subset of epithelial cells in the
      fetal lung tissue. Differentiated fetal lung explants maintained in culture
      expressed higher levels of HSD2 protein and enzymatic activity than
      undifferentiated fetal lung tissues. Finally, HSD2 protein levels were decreased
      in male, but not female, fetal lung explants treated with 17-beta estradiol. In
      contrast, 5-alpha dihydrotestosterone did not significantly affect HSD2 levels.
      These data indicate that HSD2 protein and activity levels increase in parallel
      with the differentiation of alveolar type II epithelial cells in vitro, and that
      HSD2 protein levels are regulated by 17-beta estradiol in male fetal lung tissue.

PMID- 17515841
TI  - The MRI findings of the right-sided fetal lung can be used to predict postnatal
      mortality and the requirement for extracorporeal membrane oxygenation in isolated
      left-sided congenital diaphragmatic hernia.
AB  - We evaluated whether a correlation existed between fetal pulmonary magnetic
      resonance imaging (MRI) findings and postnatal mortality, as well as the
      requirements for extracorporeal membrane oxygenation (ECMO) in infants with
      prenatally diagnosed, isolated left-sided congenital diaphragmatic hernia (CDH).
      Twenty-one pregnant women carrying fetuses with CDH underwent 30 MRI scans, and
      the right-sided fetal lung volume (FLV) was measured. In the control, a
      regression analysis was performed to associate FLV with gestational age. This
      yielded a formula that enabled the calculation of the expected right fetal lung
      volume (ERFLV). In cases with CDH, the right-sided observed FLV/ERFLV (= %RFLV)
      was compared with both the postnatal mortality and whether ECMO was required.
      Additionally, we investigated the relationship between the lung shape on MRI
      (whether there was a complete pulmonary baseline present) and postnatal
      mortality. The %RFLV was significantly lower in nonsurvivors compared with
      survivors. Among survivors, the %RFLV was significantly lower in infants who
      required ECMO compared with those who did not. The pulmonary baseline was
      completely present in 3 (38%) and 13 (100%) of the nonsurvivors and survivors,
      respectively. In isolated left-sided CDH, the %RFLV is a good predictor not only
      of postnatal mortality but also of the requirement for ECMO.

PMID- 17515842
TI  - Determination of carnitine ester patterns during the second half of pregnancy, at
      delivery, and in neonatal cord blood by tandem mass spectrometry: complex and
      dynamic involvement of carnitine in the intermediary metabolism.
AB  - We studied plasma concentrations of free carnitine and 30 carnitine esters by
      electron spray ionization (ESI) tandem mass spectrometry in 37 pregnant women at
      the 20th and 30th weeks of gestation and at delivery, and in their neonates at
      birth, and in 22 age-matched nonpregnant women. The plasma levels of
      acetylcarnitine and carnitine esters with more than five carbons were
      significantly higher, whereas the concentration of free carnitine was
      significantly lower at term than at the 20th week of pregnancy (16.75 +/- 0.89
      versus 19.61 +/- 1.25). Almost all of C2- to C12-carnitine esters were
      significantly lower, whereas C16- and C18-carnitines with in-chain modifications
      were significantly higher in mothers at delivery compared with nonpregnant women.
      Plasma levels of free carnitine and C2-, C3-, C4-, C5-, C6-, and C16-carnitines
      were significantly lower, while concentrations of carnitine esters with 8, 10, 12
      and 18 carbons in the acyl chain as well as C14:1-, C14:2-, and C16:1-OH
      carnitines were significantly higher in mothers at term than in their neonates.
      The data of the present study clearly show dynamic features of plasma carnitine
      profile during pregnancy and indicate an extraordinarily active participation of
      the carnitine in the intermediary metabolism both in the pregnant woman and in
      the neonate.

PMID- 17515843
TI  - Systemic hyperthermia induces ischemic brain injury in neonatal mice with ligated
      carotid artery and jugular vein.
AB  - Postnatal d 7 (p7) or p12 mice had their right carotid artery (CA) and jugular
      vein (JV) ligated to mimic veno-arterial (VA) access for extracorporeal membrane
      oxygenation (ECMO). At p9-11 (early) or p19-21 (late) mice were exposed to
      hyperthermia or normothermia followed by assessment of neuropathological injury
      score. In separate cohorts of mice, cerebral and peripheral blood flow (CBF, PBF)
      and cerebral ATP content was measured. Hyperthermia resulted in ischemic brain
      injury in 57% and 77% of mice subjected to early or late hyperthermia,
      respectively. Isolated CA+JV ligation induced minimal injury (score 0.47 +/-
      0.34) in 2/8 mice from the late normothermia group. No cerebral injury was
      detected in mice subjected to early normothermia. In 3/19 shams (2/10 early, 1/9
      late) hyperthermia induced a subtle (score, 0.6 +/- 0.27) injury in the
      ipsilateral to the site of surgery cortex. CBF and PBF increased in response to
      hyperthermia in all mice. The rise in CBF was significantly attenuated in the
      "ligated" versus intact hemisphere, which was associated with a profound
      depletion of ATP content. Systemic hyperthermia induces ischemic brain injury in
      mice with ligated CA+JV. We speculate that hyperthermia/fever can be a potential
      risk factor for brain injury in infants treated with VA ECMO.

PMID- 17515844
TI  - The impact of hyperoxia on the neonatal and adult developing dendritic cell.
AB  - Oxygen is essential therapy for neonates with acute respiratory failure,
      including those with infections. However, high oxygen levels may be
      counterproductive for overcoming infections because hyperoxia may kill cells,
      including dendritic cells that are essential to the emergence of the pulmonary
      immune system and pivotal in mounting immune responses to infections. We studied
      the impact of hyperoxia on developing dendritic cells from neonatal cord blood
      and adult blood monocytes, comparing viability, development of maturation, and
      endocytic function. Our data suggest that cord blood-derived dendritic cells may
      be more resistant to hyperoxic-induced cell death than adult blood-derived cells.
      Moreover, the surviving cells in either group are those that maintain an immature
      phenotype. This may impair their ability to perform optimal immune function.

PMID- 17515845
TI  - Transmaternal exposure to bisphenol a modulates the development of oral
      tolerance.
AB  - Bisphenol A (BPA) is a representative endocrine disruptor that may have adverse
      effects on human health. Since the development of oral tolerance during infancy
      may play an important role in the prevention of food allergies, we examined
      whether transmaternal exposure to BPA influences the development of oral
      tolerance. To measure antigen-specific responses, female wild-type mice mated
      with male ovalbumin (OVA)-specific T-cell receptor transgenic (TCR-tg) mice were
      fed with BPA during pregnancy and while nursing. OVA was administered to OVA-TCR
      tg offspring during their weaning period. Oral administration of both high and
      low doses of OVA suppressed OVA-specific cell proliferation and cytokine
      production in both BPA-exposed and nonexposed control mice, but the OVA-mediated
      suppression was significantly more diminished by the BPA exposure. The
      accumulation of CD4+CD25+Foxp3+ T cells was diminished in the BPA-exposed
      offspring. Moreover, after low dose OVA administration, serum OVA-specific IgG1
      and IgG2a levels were higher in the BPA-exposed offspring than in nonexposed
      ones. Taken together, our results indicate that transmaternal exposure to BPA
      seems to modulate the mechanisms underlying tolerance induction; therefore, BPA
      may partially interrupt the development of oral tolerance.

PMID- 17515846
TI  - Predictors of AVP and TSH levels and the timing of first voiding in the newborn.
AB  - To evaluate obstetric predictors of umbilical cord plasma AVP levels, serum TSH
      levels and the timing of first voiding, 87 singleton term newborns were divided
      into three groups: group A, vaginal delivery (n = 30); group B, cesarean section
      (CS) during labor (n = 26); and group C, elective CS (n = 31). The AVP
      concentration was 120 (0.7-2170) ng/L in group A, 1.8 (0.01-183) ng/L in group B,
      and 0.8 (0.01-30) ng/L in group C (p < 0.001). In group A, the TSH concentration
      was 10.20 (3.5-30.80) mU/L; in group B, 5.40 (2.10-43.00) mU/L; and in group C,
      5.30 (2.90-11.00) mU/L (p = 0.001). Duration of labor had a positive correlation
      with AVP (p < 0.001) and TSH (p = 0.001) concentrations. The timing of first
      voiding had a positive correlation with gestational age (p = 0.003), volume of
      additional feeding before first voiding (p < 0.001), and umbilical AVP
      concentration (p = 0.023). The AVP and TSH concentrations are associated with
      mode of delivery and duration of labor and AVP levels also with the timing of
      first voiding in the newborn.

PMID- 17515847
TI  - Effect of a fermented formula on thymus size and stool pH in healthy term
      infants.
AB  - To investigate the effects of fermented formula (FF) with Bifidobacterium breve
      C50 and Streptococcus thermophilus 065 on thymus size and stool pH of healthy
      term infants, ultrasound examinations and evaluations of thymus sizes and thymus
      indices (TI) and measurements of stool pH were performed in the same 90 term
      neonates on the 3rd d of life and on the 1st, 2nd, 3rd, and 4th mo of life.
      Thirty newborns were exclusively breast-fed while the remaining 60 were randomly
      assigned to receive either a FF or a standard formula (SF). The fecal pH of the
      breast-fed group was lower than the SF group (p < 0.05), although it was similar
      to that of the FF group on the third postnatal day, persisting for the entire 4
      mo of the study. The difference in TI was statistically significant over repeated
      measurements among the groups. The FF infants showed a TI similar to the breast
      fed newborns. Probiotic fermentation products have effects comparable to those of
      the bacteria composing the intestinal microflora supporting the idea that
      intestinal bacterial balance plays an important role in improving host immune
      responses.

PMID- 17515848
TI  - Heparanase pretreatment attenuates endotoxin-induced acute lung injury in rats.
AB  - A central event of systemic inflammation and septic organ injury is infiltration
      of tissues with polymorphonuclear neutrophils, likely modulated by the integrity
      of the extracellular matrix underlying the vascular endothelium. In the present
      study, the effect of matrix-modifying endoglycosidase (heparanase) on endotoxin
      (LPS)-induced inflammatory lung injury was investigated in rats. Animals were
      treated with heparanase or LPS or pretreated with heparanase before LPS
      injection, and acute lung injury was verified histologically and characterized by
      analysis of bronchoalveolar lavage fluids. Pretreatment with heparanase
      attenuated the mortality of animals and preserved the histological structure of
      the lungs. Furthermore, polymorphonuclear neutrophil accumulation and activation,
      analyzed by myeloperoxidase release and reactive oxygen species production
      associated with lung injury, were significantly reduced upon heparanase
      pretreatment. In addition, heparanase pretreatment elevated the IL-10 levels in
      the pulmonary compartment. Moreover, results from in vitro experiments have
      identified monocyte-derived IL-10 as an important mediator used by heparanase to
      suppress inflammatory reactions. The protective effect of heparanase may indicate
      a novel therapeutic strategy for sepsis.

PMID- 17515849
TI  - Lamotrigine reduces intestinal I/R injury in the rat.
AB  - I/R injury of the intestine is a life-threatening emergency with mortality rates
      still more than 60%. We have investigated the protective effect of lamotrigine
      (LTG), an antiepileptic drug, which has an established neuroprotective effect, on
      intestinal I/R injury in rats. Forty-eight Wistar albino rats were divided into
      three groups: a sham-operated group (no I/R injury; n = 16), an ischemic control
      group (I/R, n = 16), and an LTG-treated group (pretreatment 5 mg kg-1 LTG + IR; n
      = 16). A marker for lipid peroxidation, malondialdehyde, free radical scavengers,
      glutathione peroxidase, catalase, and superoxide dismutase levels, an index of
      polymorphonuclear neutrophils, myeloperoxidase activity, and mucosal damage were
      investigated. Malondialdehyde levels, myeloperoxidase activity, and the severity
      of mucosal damage were decreased in the LTG group. Moreover, in the LTG group,
      glutathione peroxidase and superoxide dismutase levels were higher compared with
      the I/R group. The pretreatment of rats with LTG before intestinal ischemia
      ameliorates the mucosal damage in intestinal I/R injury probably by altering
      lipid peroxidation, neutrophil accumulation, and antioxidant activity.

PMID- 17515850
TI  - Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in
      hemorrhagic and septic shock.
AB  - Arginine vasopressin (AVP) levels are increased in hemorrhagic and septic shock.
      Measurement of AVP levels has limitations due to its short half-life and
      cumbersome detection method. Copeptin is a more stable peptide derived from the
      same precursor molecule. We evaluated the plasma copeptin concentration in two
      independent studies: first, in an experimental baboon model of hemorrhagic shock,
      and second, in a prospective observational study of 101 consecutive critically
      ill patients at a university hospital. Copeptin was measured with a newly
      developed sandwich immunoassay using two polyclonal antibodies to the C-terminal
      region (amino acid sequence 132-164) of pre-pro-AVP. Copeptin concentrations in
      hemorrhagic shock increased markedly from median (range) of 7.5 [2.7-13) to 269
      pM (241-456 pM). After reperfusion, copeptin levels dropped within hours to a
      plateau of 27 pM (15-78 pM). In the critically ill patient cohort, copeptin
      values increased significantly with the severity of the disease and were in
      patients without sepsis [27.6 pM [2.3-297 pM]), in sepsis [50.0 pM [8.5-268 pM]),
      in severe sepsis [73.6 pM [15.3-317 pM]), and in septic shock [171.5 pM (35.1-504
      pM] compared with 4.1 pM (1.0-13.8 pM) in healthy controls (P for all vs.
      controls <0.001). On admission, circulating copeptin levels were higher in
      nonsurvivors (171.5 pM, 46.5-504.0 pM) as compared with survivors (86.8 pM, 8.5
      386.0 pM; P = 0.01). Copeptin levels correlated with basal cortisol levels (r =
      0.42; P < 0.001) and osmolality (r = 0.42; P < 0.001). In a logistic regression
      model including other covariates besides copeptin (e.g., determinants of fluid
      status) on survival, serum copeptin levels were the only independent significant
      predictor of outcome (P = 0.03). Copeptin concentrations are elevated in
      hemorrhagic and septic shock. Copeptin was higher on admission in nonsurvivors as
      compared with survivors, suggesting copeptin as a prognostic marker in sepsis.
      The availability of a reliable assay for the measurement of AVP release can also
      prove useful for the assessment of fluid and osmosis status in various diseases.

PMID- 17515852
TI  - Edema-induced intestinal dysfunction is mediated by STAT3 activation.
AB  - Increased signal transducer and activator of transcription 3 (STAT3) activation
      has been shown to be associated with intestinal dysfunction. The purpose of this
      study was to investigate the role of STAT3 in edema-induced intestinal
      dysfunction. Intestinal edema was induced in male Sprague-Dawley rats by a
      combination of mesenteric venous hypertension and fluid resuscitation (RESUS +
      VH). Resuscitation fluid alone (RESUS), venous hypertension alone (VH), and sham
      operated rats (CONTROL) were used as controls. Edema development, STAT3 DNA
      binding activity, nuclear translocation, and phosphorylation were measured in rat
      distal small intestinal muscularis. A significant amount of edema development was
      measured in the RESUS + VH rats compared with CONTROL and VH from 30 min to 6 h
      after surgery. Edema developed in the RESUS group at 30 min postsurgery but
      resolved before 2 h postsurgery. A significant increase in STAT3 DNA binding
      activity was observed from 30 min to 6 h after surgery in the edematous RESUS +
      VH group compared with nonedematous CONTROL. In addition, a significant increase
      in STAT3 nuclear translocation and phosphorylation was measured in the RESUS + VH
      group 2 and 6 h after surgery. No significant increases in STAT3 activation were
      observed in either the RESUS or VH groups compared with CONTROL. Rats in both the
      RESUS + VH and CONTROL groups were pretreated with AG490 (5 mg/kg, i.p.) to block
      STAT3 activation. Signal transducer and activator of transcription 3 inhibition
      attenuated edema-induced decrease in intestinal contractile activity and myosin
      light chain phosphorylation. We conclude from these data that edema-induced
      decreases in intestinal contractile activity are mediated, at least in part, by
      STAT3 activation.

PMID- 17515853
TI  - Absence of functional peroxisome proliferator-activated receptor-alpha enhanced
      ileum permeability during experimental colitis.
AB  - The aim of the present study was to examine the role of endogenous peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha) ligand on the permeability and
      structure of small intestine tight junctions (TJs) in an animal model of
      experimental colitis, induced by dinitrobenzene sulfuric acid (DNBS). Four days
      after colitis induction with DNBS, the ileal TJs were studied by means of
      transmission electron microscopy using lanthanum nitrate and immunohistochemistry
      of occludin, zonula occludens 1, and claudin 2. Administration of DNBS to wild
      type mice induced colon injury associated with a significant increase of plasma
      and colon tumor necrosis factor-alpha levels and with a significant increase of
      ileal permeability. Distal colitis in mice induced an increase of TJ permeability
      throughout the entire small intestine, and the extent of alterations correlates
      with colonic damage. Small intestinal permeability was associated with the
      presence of apoptosis (evaluated by FAS ligand expression and terminal
      deoxynucleotidyltransferase-mediated UTP nick end labeling coloration), which was
      associated with a significantly increased expression of proapoptotic Bax and
      decreased ileum content of antiapoptotic Bcl-2. Absence of a functional PPAR
      alpha gene in PPAR-alpha knockout mice resulted in a significant augmentation of
      all the above-described parameters. Taken together, our results clearly
      demonstrate that endogenous PPAR-alpha ligands reduced small intestinal
      permeability in experimental colitis through the regulation of apoptosis and TJ
      protein.

PMID- 17515854
TI  - Neutrophil NAD(P)H oxidase is required for hemorrhagic shock-enhanced TLR2 up
      regulation in alveolar macrophages in response to LPS.
AB  - Alveolar macrophages (AMs) play an important role in the development of
      posttrauma lung inflammation through initiating polymorphonuclear neutrophil
      (PMN) migration by direct interactions with PMN, which is in turn mediated by the
      expression of chemokines and cytokines. We have recently reported that
      hemorrhagic shock-activated PMN sensitize AM to bacteria LPS for the up
      regulation of Toll-like receptor (TLR)2; in turn, this TLR2 up-regulation results
      in the amplification of expression of cytokines and chemokines in the AM in
      response to the bacterial products LPS and peptidoglycan, associated with
      enhanced PMN sequestration in the lung. We sought to address the mechanism
      underlying the augmentation of TLR2 in AM by shock-activated PMN. We found that
      hemorrhagic shock/resuscitation (shock) followed by a low dose of i.t. LPS
      markedly increased TLR2 mRNA expression in AM in wild-type (WT) mice. In
      contrast, in mice lacking the gp91 subunit of nicotinamide adenine dinucleotide
      phosphate (reduced form) oxidase (gp91) or in neutropenic WT mice, the increase
      in TLR2 mRNA was attenuated. Coculture of AM with PMN derived from WT-shocked
      mice caused a significantly higher level of TLR2 expression in the AM in response
      to LPS. However, this increase in TLR2 expression was less evident when the AMs
      were cocultured with PMN derived from gp91 mice subjected to shock. The
      antioxidant polyethylene glycol catalase markedly decreased MyD88-dependent
      activation of IL-1 receptor associated kinase 4 and TLR2 expression in the AM in
      response to LPS. Thus, PMN nicotinamide adenine dinucleotide phosphate (reduced
      form) oxidase sensitizes hemorrhagic shock-primed AM to LPS, at least in part via
      enhancing IL-1 receptor associated kinase 4 activity.

PMID- 17515855
TI  - Effects of chronic ethanol ingestion on tight junction proteins and barrier
      function of alveolar epithelium in the rat.
AB  - Previous studies show that chronic alcohol abuse is an independent risk factor
      for acute lung injury (ALI) and impairs alveolar epithelial barrier function
      through glutathione depletion. However, the precise molecular structures that are
      damaged by chronic ethanol ingestion have not been identified. To test whether
      chronic ethanol ingestion impairs the alveolar epithelium barrier by tight
      junction protein deterioration and predisposes to ALI, this study determined the
      alterations in tight junction proteins occludin, zonula occludens (ZO)-1, and
      adherens junction protein E-cadherin in alveolar epithelium and observed the
      protective effect of glutamine (Gln) supplementation. Sixty Sprague-Dawley rats
      were assigned to control, ethanol (6 weeks' ethanol feeding), lipopolysaccharide
      ([LPS] 2 mg/kg, i.v.), ethanol plus LPS, ethanol plus Gln (0.3 g/kg, gavage
      daily), and ethanol plus Gln plus LPS groups. Treatment with both ethanol and LPS
      significantly increased bronchoalveolar epithelial permeability, and treatment
      with ethanol plus LPS further increased the permeability. Using
      immunofluorescence, immunoblotting, and reverse transcriptase-polymerase chain
      reaction, this study shows that treatment with both ethanol and LPS induced
      partial breakdown of membrane staining and decreased cytoplasm staining in
      alveolar epithelium and decreased the messenger RNA and protein expression of
      those molecules in alveolar epithelial cells. Treatment with ethanol plus LPS
      caused further deterioration. Moreover, Gln supplementation markedly attenuated
      the enhanced bronchoalveolar epithelial permeability and decreased messenger RNA
      and protein expression of those molecules induced by ethanol and ethanol plus
      LPS. These data suggest that chronic ethanol ingestion impairs the alveolar
      epithelial barrier function via occludin, ZO-1, and E-cadherin deterioration, and
      predisposes to ALI. Glutamine supplementation has protective effect.

PMID- 17515856
TI  - Effects of CD14-159 C/T polymorphism on CD14 expression and the balance between
      proinflammatory and anti-inflammatory cytokines in whole blood culture.
AB  - CD14 is an important receptor of innate immunity. When CD14 is anchored by
      ligands to LPS, peptidoglycans, or lipoteichoic acid, it can result in either
      proinflammatory or anti-inflammatory responses. To determine whether CD14-159 C/T
      polymorphism is associated with CD14 expression and the balance of
      proinflammatory and anti-inflammatory responses, we studied 118 healthy ethnic
      Han Chinese using a whole blood culture model. The CD14-159 C/T polymorphism was
      determined by polymerase chain reaction and subsequent HaeIII restriction enzyme
      digestion of the polymerase chain reaction products. Meanwhile, CD14 mRNA
      expression in leukocytes and the levels of soluble CD14, TNF-alpha, IL-6, and IL
      10 were also determined in the supernatants. Among the 118 individuals, there
      were 40 TT homozygotes, 62 heterozygotes, and 16 subjects homozygous for C
      allele. After LPS stimulation, the levels of CD14 mRNA expression in TT and TC
      genotypes were significantly higher than in CC homozygotes (P = 0.017), and
      soluble CD14 levels were also higher than in CC genotypes (P = 0.008). In
      addition, TT homozygotes had the highest LPS-stimulated TNF-alpha, IL-6
      production (P = 0.044, P = 0.004), and the lowest IL-10 release (P = 0.003). In
      conclusion, CD14-159 C/T polymorphism is correlated with CD14 expression and may
      thus influence the balance of proinflammatory and anti-inflammatory responses in
      ethnic Han Chinese. These results suggest that CD14-159 C/T polymorphism might
      partly explain the difference in predisposition to develop complications of
      infectious diseases in different patients and may provide a therapeutic target
      for sepsis intervention strategies.

PMID- 17515857
TI  - Differences in antithrombin III activities by administration method in critical
      patients with disseminated intravascular coagulation: a pharmacokinetic study.
AB  - Pharmacokinetic (PK) data for antithrombin III (AT) are limited in the critical
      patients. We therefore performed PK analysis using a two-compartment model and
      also examined whether plasma AT activity would change depending on two
      administration methods, AT agent at 500 U/8 h (divided group) or 1,500 U/24 h
      (combined group) for 3 days, a regulated dosage for disseminated intravascular
      coagulation (DIC) treatment in Japan, in critical patients with DIC. Clinical
      prospective randomized study. A high care unit in a university hospital. Twenty
      four consecutive critical patients with DIC. Ages ranged from 34 to 91 years.
      Acute physiology age and chronic health evaluation II scores were 25 to 35.
      Antithrombin III activities in the combined group caused remarkable transient
      increases but returned to near the preadministration level 24 h after the
      infusion. Antithrombin III level in the divided group showed small elevations on
      each session; therefore, steady increases were found after serial administrations
      of the agent. On the third day, AT trough activities in the divided group were
      significantly higher than those in the combined group (P = 0.005). However, peak
      AT activities in the combined group after AT administration were higher than
      those in the divided group throughout the study (P = 0.024). Aggravation of
      bleeding tendency occurred more frequently in the combined group (P = 0.03). Half
      life times on the distribution phase in both groups were remarkably shorter than
      those of previously reported control in congenital AT deficiency. This suggests
      an increased vascular permeability in the critical patients in this study.
      Distribution volume in the patients here increased significantly as compared with
      the previous controls. This is the first PK report using a two-compartment model
      to demonstrate that remarkable increases in vascular permeability and
      distribution volume occur in critical patients with DIC, and if the same dose is
      administered intermittently in such PK situation, AT administration in divided
      manner can maintain plasma AT trough activity higher than that in the combined
      method.

PMID- 17515858
TI  - Epigenetic robotics: behavioral treatments and potential new models for
      developmental pediatrics.

PMID- 17515859
TI  - Wnt5a is required for cardiac outflow tract septation in mice.
AB  - Lack of septation of the cardiac outflow tract (OFT) results in persistent
      truncus arteriosus (PTA), a form of congenital heart disease. The outflow
      myocardium expands through addition of cells originating from the pharyngeal
      mesoderm referred to as secondary/anterior heart field, whereas cardiac neural
      crest (CNC) cell-derived mesenchyme condenses to form an aortopulmonary septum.
      We show for the first time that a mutation in Wnt5a in mice leads to PTA. We
      provide evidence that Wnt5a is expressed in the pharyngeal mesoderm adjacent to
      CNC cells in both mouse and chicken embryos and in the myocardial cell layer of
      the conotruncus at the time when CNC cells begin to form the aortopulmonary
      septum in mice. Although expression domains of secondary heart field markers are
      not altered in Wnt5a mutant embryos, the expression of CNC cell marker PlexinA2
      is significantly reduced. Stimulation of CNC cells with Wnt5a protein elicits
      Ca2+ transients, suggesting that CNC cells are capable of responding to Wnt5a. We
      propose a novel model in which Wnt5a produced in the OFT by cells originating
      from the pharyngeal mesoderm signals to adjacent CNC cells during formation of
      the aortopulmonary septum through a noncanonical pathway via localized
      intracellular increases in Ca2+.

PMID- 17515860
TI  - Hypoxia induces alteration of bone morphogenetic protein receptor signaling in
      pulmonary artery endothelial cell.
AB  - Reduced expression of bone morphogenetic protein receptors (BMPR) has been
      implicated in the pathogenesis of pulmonary hypertension (PH), but changes in the
      intracellular signaling pathway of BMPR have not been fully understood. We
      hypothesized that BMPR signaling in pulmonary endothelial cells is altered during
      the development of PH, such as hypoxia-induced PH. We examined the expression of
      BMPR, BMP-regulated Smads and Id-1 in lung tissues of Sprague-Dawley rats exposed
      to 2 wk of hypoxia and in isolated lung vascular endothelial cells exposed to
      hypoxia. BMPRII was predominantly expressed in the endothelial cells (EC) of
      pulmonary vasculature. In hypoxic rats, reduced expression of BMPRII was observed
      in the EC of resistance pulmonary arteries. The expression of phosphorylated
      Smad1/5/8 and Id-1 in EC was also reduced, whereas the expression of Smad1 as
      well as activin receptor-like kinase 1 (ALK1) was up-regulated during the
      development of PH. In in vitro exposure to hypoxia, the expression of mRNA
      transcripts for BMPRII, Smad8, and Id-1 in EC was reduced, whereas mRNA of Smad1
      was not diminished. Our results suggest that hypoxia induces alteration of
      intracellular BMPR signaling in the EC of resistance pulmonary artery, which is
      involved in the pathogenesis of PH.

PMID- 17515861
TI  - RSV mediates Pseudomonas aeruginosa binding to cystic fibrosis and normal
      epithelial cells.
AB  - Cystic fibrosis lung disease typically has a course of exacerbations and
      remissions, suggesting that external factors like viral infections can influence
      this course. Clinical data suggest synergism between respiratory syncytial virus
      (RSV) infections and Pseudomonas aeruginosa in cystic fibrosis (CF) lung disease.
      We studied the influence of RSV infection on adherence of P. aeruginosa to IB3-1,
      HEp-2, and A549 epithelial cell monolayers in vitro. RSV infection of epithelial
      cells as well as simultaneous addition of RSV and P. aeruginosa to noninfected
      cells both strongly enhanced the pseudomonal adherence to epithelial cells. The
      increased adherence varied from 1.2- to 8.2-fold in case of previous RSV
      infection, and from 1.7- to 16.1-fold in case of simultaneous addition. We
      observed direct binding of RSV to P. aeruginosa, and blocking of RSV with heparin
      eliminated the effect on increased adherence. This suggests that RSV possibly
      acts as a coupling agent between P. aeruginosa and epithelial cells. In
      conclusion, RSV enhances P. aeruginosa infection of respiratory epithelial cells.
      It suggests a role of specific viral-bacterial interactions in exacerbations of
      CF lung disease, which could have important implications on prevention and
      treatment.

PMID- 17515862
TI  - In vitro transdifferentiation of human fetal type II cells toward a type I-like
      cell.
AB  - For alveolar type I cells, phenotype plasticity and physiology other than gas
      exchange await further clarification due to in vitro study difficulties in
      isolating and maintaining type I cells in primary culture. Using an established
      in vitro model of human fetal type II cells, in which the type II phenotype is
      induced and maintained by adding hormones, we assessed for transdifferentiation
      in culture toward a type I-like cell with hormone removal for up to 144 h,
      followed by electron microscopy, permeability studies, and RNA and protein
      analysis. Hormone withdrawal resulted in diminished type II cell characteristics,
      including decreased microvilli, lamellar bodies, and type II cell marker RNA and
      protein. There was a simultaneous increase in type I characteristics, including
      increased epithelial cell barrier function indicative of a tight monolayer and
      increased type I cell marker RNA and protein. Our results indicate that hormone
      removal from cultured human fetal type II cells results in transdifferentiation
      toward a type I-like cell. This model will be useful for continued in vitro
      studies of human fetal alveolar epithelial cell differentiation and phenotype
      plasticity.

PMID- 17515863
TI  - Lactoferrin induces concentration-dependent functional modulation of intestinal
      proliferation and differentiation.
AB  - Human milk stimulates intestinal development through the effects of various
      moieties. Lactoferrin (LF) is a glycoprotein of human milk whose concentration is
      highest in colostrum decreasing in mature milk. LF promotes enterocyte growth in
      intestinal cell lines. We tested the hypothesis that LF induces a distinct effect
      on enterocyte proliferation and differentiation, depending on its concentration.
      We examined the dose-related effects by human-native LF (N-LF) in Caco-2 (human
      colon adenocarcinoma) cells. At high concentrations, N-LF stimulated cell
      proliferation in immature Caco-2 cells, as judged by 3H-thymidine incorporation.
      In contrast, sucrase and lactase activities were increased at low but not high LF
      concentrations and their mRNA were also increased, indicating a transcriptional
      effect. Because iron binds specific LF sites, we compared the potency of N-LF and
      iron-saturated LF (I-LF) and found the native form more potent. Finally, we
      tested the effects by bovine LF (bLF) in the same system and found the latter
      more potent than the human isoform in inducing cell growth and lactase
      expression. These results suggest that LF directly induces enterocyte growth and
      proliferation, depending on its concentration, thereby regulating the earlyx
      postnatal intestinal development. bLF could be added to infant formula as a
      growth factor in selected intestinal diseases.

PMID- 17515864
TI  - Randomized trial of volume infusion during resuscitation of asphyxiated neonatal
      piglets.
AB  - Despite its use, there is little evidence to support volume infusion (VI) during
      neonatal cardiopulmonary resuscitation (CPR). This study compares 5% albumin
      (ALB), normal saline (NS), and no VI (SHAM) on development of pulmonary edema and
      restoration of mean arterial pressure (MAP) during resuscitation of asphyxiated
      piglets. Mechanically ventilated swine (n=37, age: 8 +/- 4 d, weight: 2.2 +/- 0.7
      kg) were progressively asphyxiated until pH <7.0, Paco2 >100 mm Hg, heart rate
      (HR) <100 bpm, and MAP <20 mm Hg. After 5 min of ventilatory resuscitation,
      piglets were randomized blindly to ALB, NS, or SHAM infusion. Animals were
      recovered for 2 h before euthanasia and lung tissue sampled for wet-to-dry weight
      ratio (W/D) as a marker of pulmonary edema. SHAM MAP was similar to VI during
      resuscitation. At 2 h post-resuscitation, MAP of SHAM (48 +/- 13 mm Hg) and ALB
      (43 +/- 19 mm Hg) was higher than NS (29 +/- 10 mm Hg; p=0.003 and 0.023,
      respectively). After resuscitation, SHAM piglets had less pulmonary edema (W/D:
      5.84 +/- 0.12 versus 5.98 +/- 0.19; p=0.03) and better dynamic compliance (Cd)
      compared with ALB or NS (Cd: 1.43 +/- 0.69 versus 0.97 +/- 0.37 mL/cm H2O,
      p=0.018). VI during resuscitation did not improve MAP, and acute recovery of MAP
      was poorer with NS compared with ALB. VI was associated with increased pulmonary
      edema. In the absence of hypovolemia, VI during neonatal resuscitation is not
      beneficial.

PMID- 17515865
TI  - Prostaglandin E2 receptor expression in fetal baboon lung at 0.7 gestation after
      betamethasone exposure.
AB  - The fetal lung produces and metabolizes prostaglandin (PG) E2. In vitro PGE2
      induces surfactant production via E prostaglandin (EP)1 and cyclic adenosine
      monophosphate (cAMP)-coupled EP (EP2 and EP4) receptors. Glucocorticoids alter PG
      function and increase lung function in preterm neonates. We hypothesized that
      fetal exposure to maternally administered betamethasone (betaM) enhances fetal
      lung EP1 and cAMP-coupled EP receptor expression. Pregnant baboons were injected
      intramuscularly (i.m.) with either betaM (n=7) or saline [control (CTR); n=8] at
      0.7 gestation. Fetal lungs were removed at cesarean section 48 h after the first
      injection. We determined mRNA levels, protein localization and abundance for all
      four PGE2 receptors by real-time polymerase chain reaction (PCR),
      immunohistochemistry, and Western blot. EP receptors were widely distributed in
      bronchiolar epithelium, bronchiolar smooth muscle, and endothelium and media of
      blood vessels, but not alveoli. Compared with CTR, betaM exposure resulted in a
      twofold EP2 mRNA decrease (p<0.05) in male fetuses only. EP1, EP3, and EP4
      receptor mRNA levels were unaffected. Western blot analysis showed no alteration
      in EP receptor protein expression. In summary, this is the first demonstration of
      the four EP receptors in fetal lung. The only change after 48-h betaM exposure
      was a gender-specific decrease in EP2 receptor mRNA.

PMID- 17515866
TI  - Polyunsaturated fatty acid supplementation alters proinflammatory gene expression
      and reduces the incidence of necrotizing enterocolitis in a neonatal rat model.
AB  - Although supplementation of preterm formula with polyunsaturated fatty acids
      (PUFA) has been shown to reduce the incidence of necrotizing enterocolitis (NEC)
      in animal models and clinical trials, the mechanisms remain elusive. We
      hypothesized that the protective effect of PUFA on NEC may be due to the ability
      of PUFA to suppress Toll-like receptor (TLR) 4 and platelet-activating factor
      receptor (PAFR) gene expression (molecules that are important in the pathogenesis
      of NEC) in epithelial cells. To investigate the efficacy of different PUFA
      preparations on NEC in a neonatal rat model, we compared the incidence of NEC
      among the four PUFA supplemented groups--A: arachidonic acid and docosahexaenoic
      acid (AA+DHA), B: egg phospholipids (EP), C: DHA, and D: control without PUFA.
      PUFA supplementation reduced the incidence of NEC and inhibited intestinal PAFR
      and TLR4 gene expression compared with the controls. To validate the in vivo
      observations, IEC-6 cells were exposed to PAF after pretreatment with AA or DHA.
      Both AA and DHA supplementation blocked PAF-induced TLR4 and PAFR mRNA expression
      in these enterocytes. These results suggest that PUFA modulates gene expression
      of key factors involved in experimental NEC pathogenesis. These effects might in
      part explain the protective effect of PUFA on neonatal NEC.

PMID- 17515867
TI  - Changes in the expression of hypothalamic lipid sensing genes in rat model of
      intrauterine growth retardation (IUGR).
AB  - Intrauterine growth retardation (IUGR) has been linked to the development of type
      2 diabetes in later life. The mechanisms underlying this phenomenon are unknown.
      Recent data suggest that some of the molecular defects underlying type 2 diabetes
      reside in the CNS. The enzyme carnitine palmitoyltransferase-1 (CPT1) regulates
      long-chain fatty acid (LCFA) entry into mitochondria, where LCFA undergo beta
      oxidation. Hypothalamic inhibition of CPT1 decreases food intake and suppresses
      endogenous glucose production. Our aim was to investigate the effects of uterine
      artery ligation, a procedure that mimics uteroplacental insufficiency, on the CNS
      expression of CPT1 and other key enzymes of LCFA metabolism. Bilateral uterine
      artery ligation was performed on d 19 of gestation in the pregnant rat; sham
      operated pregnant rats served as controls. Hypothalamus, cerebellum, hippocampus,
      and cortex were dissected and analyzed at birth by real-time PCR. Nonesterified
      fatty acid (NEFA) serum levels were significantly higher in IUGR pups (p<0.0001).
      In IUGR rats, the hypothalamic expression of CPT1 isoform C (p=0.005) and acetyl
      CoA carboxylase (ACC) isoforms alpha (p<0.05) and beta (p=0.005) were
      significantly decreased. The data presented here support the hypothesis that an
      abnormal intrauterine milieu can induce changes in hypothalamic lipid sensing.

PMID- 17515868
TI  - Effect of prenatal exposure to isoflavones on bone metabolism in mice at
      adulthood.
AB  - Early postnatal exposure to genistein resulted in improved bone health at early
      adulthood in mice. The objective of the present study was to determine whether in
      utero exposure to isoflavones also has a positive effect on bone health,
      resulting in higher bone mineral density (BMD) and greater resistance to fracture
      at adulthood. Pregnant mice received daily subcutaneous injections of genistein
      (3.75 mg), daidzein (3.75 mg), genistein (3.75 mg) + daidzein (3.75 mg), or
      vehicle from d 9 to 21 of pregnancy. At birth, offspring (n = 12/group/gender)
      remained with their respective mother and were weaned at postnatal age of 21 d
      and fed control diet, devoid of isoflavones, until 4 mo of age, at which time
      tissues were collected. There was an overall effect of treatment on femur BMD,
      which was higher (p<0.001) among control and genistein groups compared with
      daidzein and genistein + daidzein groups. Treatment did not have a significant
      effect on femur peak load. Among females, daidzein resulted in a lower (p=0.02)
      BMD of lumbar vertebra (LV) 1-4 than all other groups however peak load of LV4
      did not differ due to treatment or gender. In conclusion, in utero exposure to
      isoflavones did not result in functional benefits to bone at young adulthood.

PMID- 17515869
TI  - Global gene expression in the developing rat brain after hypoxic preconditioning:
      involvement of apoptotic mechanisms?
AB  - Exposure to hypoxia before hypoxia-ischemia (HI) confers substantial protection
      referred to as preconditioning (PC). We hypothesized that PC induces critical
      changes of genes related to apoptotic cell death to render the brain more
      resistant. PC hypoxia (8% O2, 36 degrees C, 3 h) was induced in rats on postnatal
      day (PND) 6, and the rats were killed at 0, 2, 8, and 24 h. Total RNA was
      extracted from cerebral cortex and analyzed using Affymetrix rat genome 230 2.0
      array. PC induced significant changes in 906 genes at 0 h, 927 at 2 h, 389 at 8
      h, and 114 at 24 h. Ontology analysis revealed significant alterations in genes
      involved in cell communication, signal transduction, transcription,
      phosphorylation, and transport. Genes involved in cell death/apoptosis as well as
      those related to brain development (cell differentiation, neurogenesis,
      organogenesis, blood vessel development) were overrepresented. A detailed
      analysis demonstrated that 77 significantly regulated genes were involved in
      apoptosis, specifically related to the Bcl-2 family, JNK pathway, trophic factor
      pathways, inositol triphosphate (PI3) kinase/Akt pathway, extrinsic or intrinsic
      pathway, or the p53 pathway. The study supports that the epidermal growth factor
      receptor family, mitogen-activated protein kinase phosphatases, and Bcl-2-related
      proteins and the PI3 kinase/Akt pathway may have roles in providing resistance in
      the developing central nervous system (CNS).

PMID- 17515870
TI  - A comparison of high-dose recombinant erythropoietin treatment regimens in brain
      injured neonatal rats.
AB  - Recombinant human erythropoietin (rEpo) is neuroprotective in neonatal models of
      hypoxic-ischemic brain injury. However, the optimal rEpo dose, dosing interval,
      and number of doses for reducing brain injury are still undetermined. We compared
      the neuroprotective efficacy of several subcutaneous rEpo treatment regimens.
      Seven-day-old rats underwent unilateral carotid ligation plus 90 min 8% hypoxia.
      Treatment began immediately after injury. Treatment regimens examined included 1,
      3, or 7 daily subcutaneous injections of either 0 (vehicle), 2,500, 5,000, or
      30,000 U/kg rEpo. Gross brain injury, neuronal apoptosis (TUNEL), and gliosis
      (glial fibrillary acidic protein) were assessed at 48 h or 1 wk post injury.
      Immunoreactive cells and brain injury were quantified for statistical comparison
      to vehicle controls. rEpo treatment reduced brain injury, apoptosis, and gliosis,
      in a dose-dependent U-shaped manner at both 48 h and 1 wk. Neither one injection
      of 2,500, seven injections of 5,000, or three injections of 30,000 U/kg rEpo were
      protective. Three doses of 5,000 and one dose of 30,000 U/kg rEpo were most
      protective at both time intervals. rEpo provides dose-dependent neuroprotection.
      Of the regimens tested, three doses of 5,000 U/kg was optimal because it provided
      maximal benefit with limited total exposure.

PMID- 17515871
TI  - Effects of light ethanol consumption during pregnancy: increased frequency of
      minor anomalies in the newborn and altered contractility of umbilical cord
      artery.
AB  - This study explores the effects of light maternal ethanol consumption during
      pregnancy on the appearance of minor malformations in neonates as well as on the
      contractile properties of their umbilical cord arteries (UCAs). Clinical external
      findings of newborns of women declaring light ethanol consumption during any
      period of their pregnancies [ethanol-exposed group (E group), n=79] were compared
      with those of nonexposed mothers [nonexposed to ethanol group (NE group), n=100].
      Women who smoked or had any associated pathology were excluded. E group mothers
      consumed, on average, 200-250 mL ethanol/trimester (upper limit 700
      mL/trimester). Sixty-six percent of the neonates in the E group presented at
      least one minor malformation (retromicrognathia and minor anomalies of the
      auricular/preauricular area were the more common), whereas only 16% of the NE
      group did (p=0.0000). The percentage of children exhibiting Apgar scores <7 was
      significantly greater in the E group (11% versus 2%, p=0.0119). UCAs from the E
      group developed significantly less contractile force (p<0.05) than those of the
      NE group when exposed to 1 microM serotonin (5-HT) or to a high K+ depolarizing
      solution. This difference persisted after inhibition of endothelial release of
      nitric oxide (NO) and prostacyclin. In conclusion, even light drinking should be
      considered a risk during pregnancy.

PMID- 17515872
TI  - Maternal tobacco smoking and decreased leukocytes, including dendritic cells, in
      neonates.
AB  - Maternal smoking in pregnancy is associated with respiratory diseases in the
      offspring, possibly due to prenatal influences on the developing immune system.
      We investigated whether maternal smoking in pregnancy was associated with cord
      blood leukocyte numbers, including precursor dendritic cells, adjusting for
      concomitant factors. In a prospective healthy birth cohort study, total leukocyte
      counts were reduced in neonates of smoking mothers [10.7 (8.4-13.0), n=14]
      compared with nonexposed infants [14.7 (13.7-15.7), n=74, p=0.002] [geometric
      mean cells x 10(3)/microL (95% confidence interval)]. All leukocyte subsets were
      decreased, most prominently segmented neutrophils [4.3 (2.8-5.7) versus 6.2 (5.5
      6.8), p=0.021], lymphocytes [3.8 (2.9-4.8) versus 5.0 (4.5-5.6), p=0.036], and
      myeloid precursor dendritic cells [12.7 cells/microL (9.1-17.8) versus 18.3 (15.8
      21.2), p=0.055]. These differences persisted after adjustment for possible
      confounders. Predictors of myeloid precursor dendritic cell numbers in
      multivariable models were maternal smoking (-5.1 cells/microL, p=0.042), age (
      0.5 cells/microL/y, p=0.035), and, marginally, asthma (+8.1 cells/microL,
      p=0.075). The decrease of all leukocytes in neonates of smoking mothers could be
      clinically significant and suggests a decreased cell production, increased
      peripheral recruitment, or retention in bone marrow. Given the importance of
      dendritic cells in early immune responses, their decrease might reflect an impact
      of maternal smoking on the developing fetal immune system.

PMID- 17515873
TI  - Fluctuating pressure-passivity is common in the cerebral circulation of sick
      premature infants.
AB  - Cerebral blood flow pressure-passivity results when pressure autoregulation is
      impaired, or overwhelmed, and is thought to underlie cerebrovascular injury in
      the premature infant. Earlier bedside observations suggested that transient
      periods of cerebral pressure-passivity occurred in premature infants. However,
      these transient events cannot be detected reliably by intermittent static
      measurements of pressure autoregulation. We therefore used continuous bedside
      recordings of mean arterial pressure (MAP; from an indwelling arterial catheter)
      and cerebral perfusion [using the near-infrared spectroscopy (NIRS) Hb difference
      (HbD) signal) to detect cerebral pressure-passivity in the first 5 d after birth
      in infants with birth weight <1500 g. Because the Hb difference (HbD) signal [HbD
      = oxyhemoglobin (HbO2) - Hb] correlates with cerebral blood flow (CBF), we used
      coherence between MAP and HbD to define pressure-passivity. We measured the
      prevalence of pressure-passivity using a pressure-passive index (PPI), defined as
      the percentage of 10-min epochs with significant low-frequency coherence between
      the MAP and HbD signals. Pressure-passivity occurred in 87 of 90 premature
      infants, with a mean PPI of 20.3%. Cerebral pressure-passivity was significantly
      associated with low gestational age and birth weight, systemic hypotension, and
      maternal hemodynamic factors, but not with markers of maternal infection. Future
      studies using consistent serial brain imaging are needed to define the
      relationship between PPI and cerebrovascular injury in the sick premature infant.

PMID- 17515874
TI  - End-tidal carbon monoxide levels in prematurely born infants developing
      bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is associated with an early inflammatory
      response that persists after the first week of life. Inflammatory mediators can
      induce hemoxygenase-1 with a consequent increase in carbon monoxide (CO)
      production. End-tidal CO (ETCO) levels would be elevated in infants developing
      BPD. Serial measurements of ETCO levels were attempted on d 3, 5, 7, 14, 21, and
      28 in 50 prematurely born infants (median gestational age 29 wk). Fourteen
      infants developed BPD [oxygen dependent beyond 36 wk post-menstrual age (PMA)]
      and had higher ETCO levels compared with the rest of the cohort on d 7, 14, 21,
      and 28. On d 14, the mean (SD) ETCO levels of the BPD group were 3.19 (1.11) ppm
      and 1.43 (0.61) ppm in the non-BPD group (p<0.001). An ETCO level on d 14>2.15
      ppm had a sensitivity of 80% and specificity of 92% in predicting oxygen
      dependency at 36 wk PMA. Measurement of ETCO levels in prematurely born infants
      may be useful in the prediction of BPD.

PMID- 17515875
TI  - Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and
      nonthrombocytopenic neonates.
AB  - Thrombocytopenia is frequent among sick neonates, but little is known about its
      underlying mechanisms. It is known, however, that neonatal megakaryocytes are
      smaller and of lower ploidy than their adult counterparts and that smaller
      megakaryocytes produce fewer platelets than larger, more polyploid,
      megakaryocytes. We hypothesized that neonatal megakaryocytes would not increase
      their size in response to thrombocytopenia, thus limiting the ability of neonates
      to mount a response. To test this, we obtained marrow specimens from
      thrombocytopenic and nonthrombocytopenic neonates and adults. Megakaryocytes were
      immunohistochemically stained, quantified using an eyepiece reticle, and measured
      using an image analysis system with incorporated electronic micrometer. We found
      that, after adjusting for differences in cellularity, neonates and adults had
      similar megakaryocyte concentrations. When samples from the same sources were
      compared (tibial clot and vertebral body sections in neonates, iliac crest
      biopsies in adults), there were also no differences in megakaryocyte
      concentration between thrombocytopenic and nonthrombocytopenic subjects. The
      megakaryocyte diameter, however, was greater in adults than in neonates (19.4 +/-
      3.0 versus 15.3 +/- 1.7 microm, p<0.0001). Thrombocytopenic adults also had a
      higher proportion of large megakaryocytes than nonthrombocytopenic adults
      (p<0.001). This was not observed among thrombocytopenic neonates, suggesting a
      developmental limitation in their ability to increase megakaryocyte size.

PMID- 17515876
TI  - Brain representation of active and passive hand movements in children.
AB  - Several functional neuroimaging studies have been performed exploring the
      sensorimotor function in children with neurologic disorders. However, little is
      known about normal activation patterns of the sensorimotor system at a young age.
      We explored brain representation of active and passive hand movements in school
      age children and young adults. Nine healthy children (7-15 y) and six adults were
      studied. Functional magnetic resonance imaging (fMRI) data were acquired on a 1.5
      T scanner in block designs. Active movement consisted of repetitive opening and
      closing of the hand; passive movement consisted of the same movement performed by
      the examiner. Both hands were assessed separately. The pattern of brain
      activation (contralateral primary sensorimotor cortex (SMC), ipsilateral
      cerebellum, supplementary motor area (SMA), and lateral premotor cortex (PMC) was
      generally more widespread in the adult group, suggesting a developmental course
      in the organization of both motor and sensory cortex. Surprisingly, no difference
      was generally detected when contrasting active versus passive tasks. Our results
      suggest that active and passive hand movements can be used for the exploration of
      the sensorimotor system in children. Passive and active tasks confirmed to be
      tightly coupled, thus supporting the idea of the former as a helpful performance
      independent paradigm in the study of brain reorganization and presurgical
      assessment.

PMID- 17515877
TI  - The effect of brief exercise on circulating CD34+ stem cells in early and late
      pubertal boys.
AB  - We tested the hypothesis that exercise could stimulate CD34+ peripheral blood
      hematopoietic stem cells (PBSC) in children. Fourteen early pubertal boys (EP,
      age 10.3 +/- 0.3 y) and 13 late pubertal boys (LP, age 16.5 +/- 0.4 y) performed
      20 min of moderate-to-vigorous cycle ergometer exercise. Blood was drawn before
      and after exercise. Cells were stained for surface CD34+. Plasma granulocyte
      colony stimulating factor (G-CSF), Fms-like tyrosine kinase-3 (FLT-3), and
      stromal cell-derived factor-1 (SDF-1) were measured using ELISA. Exercise
      substantially increased PBSC (in EP from 112 +/- 21 to 182 +/- 30 cells/microL,
      p=0.0007; in LP from 63 +/- 8 to 152 +/- 21, p=0.0008), and to a smaller extent
      FLT-3 (in EP from 98 +/- 5 to 110 +/- 6 pg/mL, p<0.0001; in LP from 73 +/- 6 to
      92 +/- 6, p<0.0001) and G-CSF (in EP from 26 +/- 4 to 29 +/- 4 pg/mL, p<0.0001;
      in LP from 14 +/- 1 to 18 +/- 1, p<0.0001). Baseline levels of PBSC, FLT-3, and G
      CSF were significantly higher in EP. Exercise increased SDF-1 alpha only in LP,
      and the FLT-3 increase was greater in LP than EP. Brief exercise affects PBSC and
      PBSC mediators in children.

PMID- 17515878
TI  - Reduced sympathetic metabolites in urine of obese patients with
      craniopharyngioma.
AB  - Severe obesity is a major problem in patients suffering from craniopharyngioma
      (CP), a benign tumor located in pituitary and hypothalamic regions. In this
      study, the hypothesis that hypothalamic damage leads to a reduction in overall
      sympathetic tone was tested. Catecholamines, as well as their metabolites
      homovanillic acid (HVA) and vanillylmandelic acid (VMA), markers of catecholamine
      turnover, were measured in morning voided urine of 109 patients participating in
      a German pediatric CP study, and their physical activity was analyzed using a
      questionnaire. HVA and VMA results were compared with age-matched HVA and VMA in
      urine of patients proven to not have a catecholamine-secreting tumor. Patients
      with the most severe obesity displayed the lowest urine HVA and VMA values.
      Patients with hypothalamic CP had 3.2-fold higher BMI values (p<0.0001), lower
      HVA (0.72-fold, p<0.001), and VMA (0.84-fold, p<0.01) values, and significantly
      lower activity scores than those without hypothalamic involvement, but their
      epinephrine- and norepinephrine/creatinine ratios were not significantly
      different, possibly due to low levels. The low HVA and VMA values suggest
      decreased sympathetic outflow contributing to reduced physical activity and
      severe obesity, especially in patients with a hypothalamic tumor. In further
      studies investigating treatment options for hypothalamic obesity, disturbed
      sympathetic tone should be considered.

PMID- 17515879
TI  - The cold, hard truth about pediatric research.

PMID- 17515880
TI  - Increased oxidative stress in diabetes regulates activation of a small molecular
      weight G-protein, H-Ras, in the retina.
AB  - PURPOSE: Increased superoxide levels are implicated in the pathogenesis of
      diabetic retinopathy. We have shown that functional activation of a small
      molecular weight G-protein, H-Ras, is one of the signaling steps involved in
      glucose-induced apoptosis of retinal capillary cells. The goal of this study was
      to elucidate the mechanism(s) by which oxidative stress could result in the
      activation of H-Ras in diabetes. METHODS: Experiments were performed in isolated
      retinal endothelial cells that were treated with H(2)O(2), or the cells in which
      glucose-induced superoxide accumulation was inhibited either by superoxide
      dismutase mimetic (MnTBAP) or by overexpressing mitochondrial superoxide
      dismutase (MnSOD). The in vitro experiments were complemented with in vivo
      experiments using the retina from mice overexpressing MnSOD. RESULTS: H(2)O(2)
      activated H-Ras and its downstream signaling pathway, including Raf-1 and
      phosphorylation of p38 (p-p38) MAP kinase. Inhibition of superoxide significantly
      attenuated glucose-induced activation of H-Ras, Raf-1 and p-p38 MAP kinase.
      Overexpression of MnSOD in mice prevented diabetes-induced activation of both H
      Ras and p-p38 MAP kinase. CONCLUSIONS: Our results clearly indicate that the
      activation of H-Ras and its downstream signaling pathway in the retina and its
      vasculature could be under the control of superoxide, and H-Ras activation in
      diabetes can be prevented by inhibiting superoxide accumulation.

PMID- 17515881
TI  - Genetic variations in the hotspot region of RS1 gene in Indian patients with
      juvenile X-linked retinoschisis.
AB  - PURPOSE: X-linked juvenile retinoschisis (XLRS) is the leading cause of macular
      degeneration in males. This condition is caused by mutations in the RS1 gene and
      is, characterized by schisis within the retina. The purpose of this study was to
      identify the mutations in the RS1 gene associated with XLRS in an Indian cohort.
      METHODS: The coding region of RS1 was analyzed for mutations by polymerase chain
      reaction-single strand conformational polymorphism (PCR-SSCP) and restriction
      fragment length polymorphism (RFLP) analysis in six unrelated subjects clinically
      diagnosed as having XLRS and in their available family members. Direct sequencing
      was performed for all samples that displayed an electrophoretic mobility shift in
      SSCP gel. RESULTS: Mutation analysis of RS1 gene revealed five mutations in exon
      6 like c.574C>T, c.583A>G, c.608C>T, c.617G>A, and c.637C>T, respectively, among
      them four missense mutations, one nonsense mutation, and two novel sequence
      variations. These mutations were found in individuals who exhibited clinical
      features of bilateral foveal and peripheral retinoschisis consistent with XLRS.
      The mutations were absent in the 100 age matched control samples analyzed.
      CONCLUSIONS: This is the first report of mutations in RS1 to be associated with
      XLRS in the Indian population. The identified genetic variations, phenotype and
      genotype correlations were consistent with other studies. Identification of the
      causative mutation in patients with XLRS is helpful in confirming the diagnosis
      and in counseling of family members.

PMID- 17515882
TI  - Pro370Leu mutant myocilin disturbs the endoplasm reticulum stress response and
      mitochondrial membrane potential in human trabecular meshwork cells.
AB  - PURPOSE: To investigate the impact of Pro370Leu mutant myocilin on endoplasmic
      reticulum (ER) stress response and mitochondria function in human trabecular
      meshwork (HTM) cells. METHODS: HTM cells were transfected with wild-type
      Pro370Leu mutant myocilin or pcDNA3.1 (+) expression plasmids. The effect of the
      mutant myocilin on ER stress response was semiquantitatively evaluated by
      determining the expression level of 78 kDa glucose-regulated protein (GRP78)
      using reverse transcription-polymerase chain reaction and phosphorylation of the
      alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) using
      western blot analysis. Mitochondria function was determined by analyzing the
      changes in mitochondrial membrane potential (Deltapsim), measured by flow
      cytometry analysis using the fluorescent probe JC-1. RESULTS: Pro370Leu mutant
      myocilin attenuated the induction of GRP78 and the phosphorylation of eIF2alpha.
      In HTM cells expressing the mutant myocilin, the reductions were evident in the
      level of GRP78 mRNA (65.5+/-2.0%), GRP78 protein (22.5+/-2.3%), and eIF2alpha
      phosphorylation (30.6+/-2.6%), compared to cells transfected with the wild-type
      myocilin plasmid (p less than or equal to 0.05). There was no significant
      difference between wild-type-myocilin- and pcDNA3.1(+)-transfected cells.
      Furthermore, Pro370Leu mutant myocilin caused a collapse of Deltapsim in HTM
      cells. CONCLUSIONS: Pro370Leu mutant myocilin down-regulates the ER stress
      response and destroys the Deltapsim of HTM cells. These observations suggest that
      Pro370Leu mutant myocilin could affect ER and mitochondria function through a
      gain of function, increasing its vulnerability to various cellular injuries and
      producing dysfunctional HTM cells.

PMID- 17515883
TI  - Cyclooxygenase 2 expression in pterygium.
AB  - PURPOSE: Following the recent discovery of an abnormal expression of the p53 gene
      in the epithelium in pterygium, some researchers felt that pterygium is a tumor
      rather than a degenerative disease. Ultraviolet (UV) radiation has been reported
      to be associated with pterygium formation, however the mechanism whereby UV
      induces uncontrolled proliferation in pterygial cells is unclear. Because
      cyclooxygenase 2 (COX 2) was reported to exist and play an important role in UV
      related cutaneous carcinogenesis, it is logical to suspect that COX 2 existed in
      pterygium. This study was designed to investigate the expression of COX 2 in
      pterygium. METHODS: Immunohistochemical staining using a monoclonal antibody to
      COX 2 was performed on 90 pterygial specimens, 40 normal conjunctiva, and 5
      normal limbus. RESULTS: In the pterygium group, 75 (83.3%) specimens stained
      positive for COX 2. The staining was limited to the cytoplasm of the epithelial
      layer and predominantly over the basal epithelial layer. No substantial staining
      was visible in the subepithelial fibrovascular layers. All specimens were
      negative in the normal conjunctiva and limbus group. CONCLUSIONS: The present
      study showed COX 2 existed in pterygium. Given the role of COX 2 in cutaneous
      tumor carcinogenesis, we suggest COX 2 may also play a role in pterygium
      formation. This study could be used as the basis for future surveys of the causal
      relationship between COX 2 and pterygium as well as the effect of COX 2 inhibitor
      in preventing primary or recurrent pterygium.

PMID- 17515884
TI  - Novel LMX1B mutation in familial nail-patella syndrome with variable expression
      of open angle glaucoma.
AB  - PURPOSE: To describe the genetic and clinical findings in a large Spanish
      pedigree with nail-patella syndrome (NPS) and to investigate the expressivity of
      open angle glaucoma (OAG) in the family members. METHODS: All individuals
      underwent a complete ophthalmologic examination, including optical coherence
      tomography (OCT) of the optic disc and peripapillary region and ultrasound
      pachymetry. Screening for mutations in the LMX1B gene was performed by denaturing
      gradient gel electrophoresis and direct genomic sequencing analysis. RESULTS: Ten
      family members had NPS, seven with varying degrees of ocular hypertension (OHT).
      Only one of these had advanced OAG. The others showed high pachymetry values and
      OCT retinal nerve fiber layer (RNFL) thickness above the normal values. Screening
      for mutations in the exonic and flanking sequences of the LMX1B gene showed a
      deletion of one G (289delG) within the coding sequence of exon 3 at codon 97,
      resulting in a frame shift that creates a premature stop at codon 105
      (E97fsX105), predicting a truncated protein. This mutation was present in all NPS
      patients and absent in the unaffected family members. CONCLUSIONS: A novel
      mutation in the homeobox transcription factor LMX1B causes NPS in a family with
      variable expressivity of the syndrome, including OAG. The pathogenic mechanism
      resulting from the mutation is presumably haploinsufficiency rather than a
      dominant negative effect, which would explain the clinical variability in this
      family. All NPS OHT patients had considerably thick corneas and RNFL.

PMID- 17515885
TI  - Effects of promyelocytic leukemia zinc finger protein on the proliferation of
      cultured human corneal endothelial cells.
AB  - PURPOSE: To determine whether the promyelocytic leukemia zinc finger (PLZF)
      protein, a transcriptional repressor and negative regulator during cell cycling,
      plays a role in the proliferation of cultured human corneal endothelial cells
      (HCECs). METHODS: The expressions of the mRNA and the protein of PLZF were
      determined by real-time PCR and western blot analysis, respectively. The changes
      in the expression of the PLZF gene of cultured HCECs were investigated at
      different times after cell-cell contacts were disrupted by incubation with EDTA.
      The cell proliferation rate was assessed with a real-time cell electronic sensing
      (RT-CES) system after cultured HCECs were infected with either PLZF or LacZ
      encoding adenovirus vector (Ad-PLZF or Ad-LacZ). The PLZF-regulating genes were
      analyzed by DNA microarray analysis in cultured HCECs infected with Ad-PLZF.
      RESULTS: The expression of the mRNA of PLZF was first detected when the cultured
      HCECs became confluent, and the relative amount of PLZF mRNA continued to
      increase for up to 5 days as the cell-cell contacts were formed more firmly. On
      the other hand, the expression of the mRNA of PLZF decreased about 20 fold 3 h
      after EDTA exposure, and gradually returned to the original level as the cell
      cell contacts were reformed at 72 h after the exposure. The assessment using the
      RT-CES system showed that the proliferation of cultured HCECs was inhibited for
      up to 72 h when infected by Ad-PLZF. DNA microarray analysis revealed that the
      transforming growth factor-beta stimulated clone 22 (TSC-22) gene was up
      regulated by 2.32 fold when infected by Ad-PLZF. CONCLUSIONS: These findings
      indicate that the expression of PLZF in HCECs is closely related to the formation
      of cell-cell contacts, and that PLZF may play a role in suppressing their
      proliferation.

PMID- 17515887
TI  - Treating dyslipidemia of the metabolic syndrome: where's the evidence?

PMID- 17515886
TI  - The chemokine receptor CCR7 mediates corneal antigen-presenting cell trafficking.
AB  - PURPOSE: Trafficking of corneal antigen-presenting cells (APC) to draining lymph
      nodes (LN) is critical in triggering immune responses. However, very little is
      known about the molecular regulation of this pathway. We investigated the
      expression and function of the chemokine receptor CCR7 in mediating corneal APC
      migration in inflammation. METHODS: Expression of CCR7 and its ligands, CCL21 and
      CCL19, in the normal and inflamed corneas was analyzed by RT-PCR and
      immunofluorescence staining. The phenotype of CCR7-expressing cells was
      identified by double-staining with different cell surface markers. To trace the
      trafficking of APC to draining LN, we injected corneal grafts with Alexa488
      conjugated ovalbumin (OVA) and transplanted to syngeneic recipients. CCR7
      expression on the Alexa488-conjugated OVA+ cells in the ipsilateral draining LN
      was analyzed by flow cytometry. To determine the functional role of CCR7, we
      injected anti-CCL21 neutralizing antibody subconjunctivally after corneal
      transplantation and analyzed changes in numbers of OVA+ cells in the draining LN.
      Each experiment was repeated at least three times. RESULTS: Both CCR7 and its
      ligand CCL21 were significantly upregulated in inflamed corneas as measured by RT
      PCR and immunofluorescence staining. CCR7+ cells were detected especially in the
      corneal periphery near LYVE-1+ lymphatic vessels. CCR7+ cells were universally
      CD11b+CD11c+, and a majority were major histocompatibility complex class II
      positive, suggesting a monocytic dendritic cell lineage and a relative state of
      maturation. Forty-eight h after syngeneic transplantation with OVA-loaded grafts,
      CCR7 expression was detected on the OVA+ cells in both the host corneal beds and
      the draining LN. Local administration of anti-CCL21 led to a significant
      suppression in the flow of OVA+CD11c+ cells to the draining LN. CONCLUSIONS:
      These data suggest that in inflammation, APC expressing CCR7 on their cell
      surface interact with CCL21 to facilitate their migration from the cornea to
      draining LN via afferent lymphatics.

PMID- 17515888
TI  - Ovulation induction in women with polycystic ovary syndrome.

PMID- 17515889
TI  - Is metformin the treatment of choice for anovulation in polycystic ovary
      syndrome?

PMID- 17515890
TI  - Nonalcoholic fatty liver disease: from pathogenesis to patient care.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in
      Western countries. It encompasses a wide spectrum of liver lesions, from pure
      steatosis to end-stage liver disease with cirrhosis and hepatocellular carcinoma.
      Nonalcoholic steatohepatitis corresponds only to one stage of NAFLD. As NAFLD can
      be considered a liver manifestation of the metabolic syndrome, its prevalence is
      high in obese people and in patients who have type 2 diabetes-insulin resistance
      is one of the key elements of the pathogenesis of NAFLD. This disease is often
      asymptomatic in the absence of decompensated cirrhosis, but should be suspected
      in patients with elevated aminotransferase levels or radiological evidence of a
      fatty liver or hepatomegaly. Liver fibrosis is associated with age over 50 years,
      obesity, diabetes and high triglyceride levels. Liver biopsy is the only way to
      assess the histologic features of necrotic inflammation and fibrosis that define
      nonalcoholic steatohepatitis and to determine its probable prognosis. The
      prognosis is good for pure steatosis, whereas the presence of necrotic
      inflammation is associated with a significant risk of progression to cirrhosis
      and, possibly, hepatocellular carcinoma. Lifestyle changes, such as dietary
      modifications and exercise, are recommended. To date, there have been very few
      randomized, placebo-controlled trials of drug treatments for NAFLD.

PMID- 17515891
TI  - Therapy insight: management of Graves' disease during pregnancy.
AB  - The diagnosis of Graves' disease in pregnancy can be complex because of normal
      gravid physiologic changes in thyroid hormone metabolism. Mothers with active
      Graves' disease should be treated with antithyroid drugs, which impact both
      maternal and fetal thyroid function. Optimally, the lowest possible dose should
      be used to maintain maternal free thyroxine levels at or just above the upper
      limit of the normal nonpregnant reference range. Fetal thyroid function depends
      on the balance between the transplacental passage of thyroid-stimulating maternal
      antibodies and thyroid-inhibiting antithyroid drugs. Elevated levels of serum
      maternal anti-TSH-receptor antibodies early in the third trimester are a risk
      factor for fetal hyperthyroidism and should prompt evaluation of the fetal
      thyroid by ultrasound, even in women with previously ablated Graves' disease.
      Maternal antithyroid medication can be modulated to treat fetal hyperthyroidism.
      Serum TSH and either total or free thyroxine levels should be measured in fetal
      cord blood at delivery in women with active Graves' disease, and those with a
      history of (131)I-mediated thyroid ablation or thyroidectomy who have anti-TSH
      receptor antibodies. Neonatal thyrotoxicosis can occur in the first few days of
      life after clearance of maternal antithyroid drug, and can last for several
      months, until maternal antibodies are also cleared.

PMID- 17515892
TI  - Mechanisms of disease: glucocorticoids, their placental metabolism and fetal
      'programming' of adult pathophysiology.
AB  - Epidemiological evidence suggests that an adverse prenatal environment
      permanently 'programs' physiology and increases the risk of cardiovascular,
      metabolic, neuroendocrine and psychiatric disorders in adulthood. Prenatal stress
      or exposure to excess glucocorticoids might provide the link between fetal
      maturation and adult pathophysiology. In a variety of animal models, prenatal
      stress, glucocorticoid exposure and inhibition (or knockout of) 11beta
      hydroxysteroid dehydrogenase type 2 (11beta-HSD2)--the fetoplacental barrier to
      maternal glucocorticoids--reduce birth weight and cause increases in adult blood
      pressure, glucose levels, hypothalamic-pituitary-adrenal (HPA) axis activity and
      anxiety-related behaviors. In humans, mutations in the gene that encodes 11beta-
      hydroxysteroid dehydrogenase type 2 are associated with low birth weight. Babies
      with low birth weight have higher plasma cortisol levels throughout life, which
      indicates HPA-axis programming. In human pregnancy, severe maternal stress
      affects the offspring's HPA axis and is associated with neuropsychiatric
      disorders; moreover, maternal glucocorticoid therapy alters offspring brain
      function. The molecular mechanisms that underlie prenatal programming might
      reflect permanent changes in the expression of specific transcription factors,
      including the glucocorticoid receptor; tissue specific effects reflect
      modification of one or more of the multiple alternative first exons or promoters
      of the glucocorticoid receptor gene. Intriguingly, some of these effects seem to
      be inherited by subsequent generations that are unexposed to exogenous
      glucocorticoids at any point in their lifespan from fertilization, which implies
      that these epigenetic effects persist.

PMID- 17515893
TI  - Diabetes insipidus as a complication after pituitary surgery.
AB  - BACKGROUND: A 28-year-old woman presented with new-onset vertigo and diplopia
      that had started 2 weeks previously. An MRI scan of the brain revealed an 11 x 9
      x 9 mm sellar mass that extended into the suprasellar region. Evaluation of
      pituitary function showed mild central hypothyroidism and secondary adrenal
      insufficiency. The patient underwent trans-sphenoidal resection of the mass
      without any significant intraoperative complications. On postoperative day 1 she
      abruptly developed polyuria, hypernatremia and urine hypo-osmolality.
      INVESTIGATIONS: Measurements of plasma and urine osmolality, urine specific
      gravity, and serum sodium levels. DIAGNOSIS: Postoperative diabetes insipidus
      with a triphasic pattern. MANAGEMENT: The patient's diabetes insipidus was
      initially treated with intravenous desmopressin, and her fluid status, serum
      sodium levels, and serum and urine osmolality were carefully monitored. During
      the second, antidiuretic phase, desmopressin was discontinued and the patient's
      fluid intake was restricted. After recurrence of diabetes insipidus during the
      third phase, the patient was treated with intranasal desmopressin and was
      discharged. She remains on desmopressin therapy for chronic diabetes insipidus.

PMID- 17515894
TI  - Restoration of cone vision in a mouse model of achromatopsia.
AB  - Loss of cone function in the central retina is a pivotal event in the development
      of severe vision impairment for many prevalent blinding diseases. Complete
      achromatopsia is a genetic defect resulting in cone vision loss in 1 in 30,000
      individuals. Using adeno-associated virus (AAV) gene therapy, we show that it is
      possible to target cones and rescue both the cone-mediated electroretinogram
      response and visual acuity in the Gnat2 ( cpfl3 ) mouse model of achromatopsia.

PMID- 17515895
TI  - Targeting calcineurin activation as a therapeutic strategy for T-cell acute
      lymphoblastic leukemia.
AB  - Calcineurin is a calcium-activated serine/threonine phosphatase critical to a
      number of developmental processes in the cardiovascular, nervous and immune
      systems. In the T-cell lineage, calcineurin activation is important for pre-T
      cell receptor (TCR) signaling, TCR-mediated positive selection of thymocytes into
      mature T cells, and many aspects of the immune response. The critical role of
      calcineurin in the immune response is underscored by the fact that calcineurin
      inhibitors, such as cyclosporin A (CsA) and FK506, are powerful
      immunosuppressants in wide clinical use. We observed sustained calcineurin
      activation in human B- and T-cell lymphomas and in all mouse models of lymphoid
      malignancies analyzed. In intracellular NOTCH1 (ICN1)- and TEL-JAK2-induced T
      cell lymphoblastic leukemia, two mouse models relevant to human malignancies, in
      vivo inhibition of calcineurin activity by CsA or FK506 induced apoptosis of
      leukemic cells and rapid tumor clearance, and substantially prolonged mouse
      survival. In contrast, ectopic expression of a constitutively activated mutant of
      calcineurin favored leukemia progression. Moreover, CsA treatment induced
      apoptosis in human lymphoma and leukemia cell lines. Thus, calcineurin activation
      is critical for the maintenance of the leukemic phenotype in vivo, identifying
      this pathway as a relevant therapeutic target in lymphoid malignancies.

PMID- 17515896
TI  - Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor
      antagonists.
AB  - Exotoxins of Staphylococcus aureus belong to a family of bacterial proteins that
      act as superantigens by activating a large subset of the T-cell population,
      causing massive release of inflammatory cytokines. This cascade can ultimately
      result in toxic shock syndrome and death. Therapeutics targeting the early stage
      of the pathogenic process, when the superantigen binds to its receptor, could
      limit the severity of disease. We engineered picomolar binding affinity agents to
      neutralize the potent toxin staphylococcal enterotoxin B (SEB). A single
      immunoglobulin-like domain of the T-cell receptor (variable region, Vbeta) was
      subjected to multiple rounds of directed evolution using yeast display. Soluble
      forms of the engineered Vbeta proteins produced in Escherichia coli were
      effective inhibitors of SEB-mediated T-cell activation and completely neutralized
      the lethal activity of SEB in animal models. These Vbeta proteins represent an
      easily produced potential treatment for diseases mediated by bacterial
      superantigens.

PMID- 17515897
TI  - Abrogation of nuclear receptors Nr4a3 and Nr4a1 leads to development of acute
      myeloid leukemia.
AB  - Nur77 (NR4A1) and Nor-1 (NR4A3) are highly homologous orphan nuclear receptors
      that regulate the transcription of overlapping target genes. The transcriptional
      activity of both proteins is regulated in a ligand-independent manner by cell-
      and stimulus-specific gene induction and protein phosphorylation. Nor-1 and Nur77
      have been implicated in a variety of cellular processes, including the
      transduction of hormonal, inflammatory, mitogenic, apoptotic and differentiative
      signals. Cellular responses to these proteins suggest that they may function as
      homeostatic regulators of proliferation, apoptosis and differentiation, and thus
      may regulate cellular susceptibility to tumorigenesis. Their physiological
      functions, however, remain poorly understood. Here we describe a previously
      unsuspected function of Nor-1 and Nur77-as critical tumor suppressors of myeloid
      leukemogenesis. The abrogation of these proteins in mice led to rapidly lethal
      acute myeloid leukemia (AML), involving abnormal expansion of hematopoietic stem
      cells (HSCs) and myeloid progenitors, decreased expression of the AP-1
      transcription factors JunB and c-Jun and defective extrinsic apoptotic (Fas-L and
      TRAIL) signaling. We found that downregulation of NR4A3 ( NOR-1 ) and NR4A1 (
      NUR77 ) was a common feature in leukemic blasts from human AML patients,
      irrespective of karyotype. Thus Nor-1 and Nur77 may provide potential targets for
      therapeutic intervention in AML.

PMID- 17515898
TI  - Shape conveyed by visual-to-auditory sensory substitution activates the lateral
      occipital complex.
AB  - The lateral-occipital tactile-visual area (LOtv) is activated when objects are
      recognized by vision or touch. We report here that the LOtv is also activated in
      sighted and blind humans who recognize objects by extracting shape information
      from visual-to-auditory sensory substitution soundscapes. Recognizing objects by
      their typical sounds or learning to associate specific soundscapes with specific
      objects do not activate this region. This suggests that LOtv is driven by the
      presence of shape information.

PMID- 17515899
TI  - Supralinear increase of recurrent inhibition during sparse activity in the
      somatosensory cortex.
AB  - The balance between excitation and inhibition in the cortex is crucial in
      determining sensory processing. Because the amount of excitation varies,
      maintaining this balance is a dynamic process; yet the underlying mechanisms are
      poorly understood. We show here that the activity of even a single layer 2/3
      pyramidal cell in the somatosensory cortex of the rat generates widespread
      inhibition that increases disproportionately with the number of active pyramidal
      neurons. This supralinear increase of inhibition results from the incremental
      recruitment of somatostatin-expressing inhibitory interneurons located in layers
      2/3 and 5. The recruitment of these interneurons increases tenfold when they are
      excited by two pyramidal cells. A simple model demonstrates that the distribution
      of excitatory input amplitudes onto inhibitory neurons influences the sensitivity
      and dynamic range of the recurrent circuit. These data show that through a highly
      sensitive recurrent inhibitory circuit, cortical excitability can be modulated by
      one pyramidal cell.

PMID- 17515900
TI  - Multiple climbing fibers signal to molecular layer interneurons exclusively via
      glutamate spillover.
AB  - Spillover of glutamate under physiological conditions has only been established
      as an adjunct to conventional synaptic transmission. Here we describe a pure
      spillover connection between the climbing fiber and molecular layer interneurons
      in the rat cerebellar cortex. We show that, instead of acting via conventional
      synapses, multiple climbing fibers activate AMPA- and NMDA-type glutamate
      receptors on interneurons exclusively via spillover. Spillover from the climbing
      fiber represents a form of glutamatergic volume transmission that could be
      triggered in a regionalized manner by experimentally observed synchronous
      climbing fiber activity. Climbing fibers are known to direct parallel fiber
      synaptic plasticity in interneurons, so one function of this spillover is likely
      to involve controlling synaptic plasticity.

PMID- 17515901
TI  - Increased structural connectivity in grapheme-color synesthesia.
AB  - Diffusion tensor imaging allowed us to validate for the first time the hypothesis
      that hyperconnectivity causes the added sensations in synesthesia. Grapheme-color
      synesthetes (n = 18), who experience specific colors with particular letters or
      numbers (for example, 'R is sky blue'), showed greater anisotropic diffusion
      compared with matched controls. Greater anisotropic diffusion indicates more
      coherent white matter. Anisotropy furthermore differentiated subtypes of grapheme
      color synesthesia. Greater connectivity in the inferior temporal cortex was
      particularly strong for synesthetes who see synesthetic color in the outside
      world ('projectors') as compared with synesthetes who see the color in their
      'mind's eye' only ('associators'). In contrast, greater connectivity (as compared
      with non-synesthetes) in the superior parietal or frontal cortex did not
      differentiate between subtypes of synesthesia. In conclusion, we found evidence
      that increased structural connectivity is associated with the presence of
      grapheme-color synesthesia, and has a role in the subjective nature of
      synesthetic color experience.

PMID- 17515902
TI  - BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after
      NMDA receptor activation.
AB  - The N-methyl-D-aspartate receptor (NMDAR), brain-derived neurotrophic factor
      (BDNF), postsynaptic density protein 95 (PSD-95) and phosphatidylinositol 3
      kinase (PI3K) have all been implicated in long-term potentiation. Here we show
      that these molecules are involved in a single pathway for synaptic potentiation.
      In visual cortical neurons in young rodents, the neurotrophin receptor TrkB is
      associated with PSD-95. When BDNF is applied to cultured visual cortical neurons,
      PSD-95-labeled synaptic puncta enlarge, and fluorescent recovery after
      photobleaching (FRAP) reveals increased delivery of green fluorescent protein
      tagged PSD-95 to the dendrites. The recovery of fluorescence requires TrkB,
      signaling through PI3K and the serine-threonine kinase Akt, and an intact Golgi
      apparatus. Stimulation of NMDARs mimics the PSD-95 trafficking that is induced by
      BDNF but requires active BDNF and PI3K. Furthermore, local dendritic contact with
      a BDNF-coated microsphere induces PSD-95 FRAP throughout the dendrites of the
      stimulated neuron, suggesting that this mechanism induces rapid neuron-wide
      synaptic increases in PSD-95 and refinement whenever a few robust inputs activate
      the NMDAR-BDNF-PI3K pathway.

PMID- 17515903
TI  - Interaction with the BRCA2 C terminus protects RAD51-DNA filaments from
      disassembly by BRC repeats.
AB  - BRCA2 has an essential function in DNA repair by homologous recombination,
      interacting with RAD51 via short motifs in the middle and at the C terminus of
      BRCA2. Here, we report that a conserved 36-residue sequence of human BRCA2
      encoded by exon 27 (BRCA2Exon27) interacts with RAD51 through the specific
      recognition of oligomerized RAD51 ATPase domains. BRCA2Exon27 binding stabilizes
      the RAD51 nucleoprotein filament against disassembly by BRC repeat 4. The
      protection is specific for RAD51 filaments formed on single-stranded DNA and is
      lost when BRCA2Exon27 is phosphorylated on Ser3291. We propose that productive
      recombination results from the functional balance between the different RAD51
      binding modes [corrected] of the BRC repeat and exon 27 regions of BRCA2. Our
      results further suggest a mechanism in which CDK phosphorylation of BRCA2Exon27
      at the G2-M transition alters the balance in favor of RAD51 filament disassembly,
      thus terminating recombination.

PMID- 17515904
TI  - Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2.
AB  - The human breast cancer susceptibility gene BRCA2 is required for the regulation
      of RAD51-mediated homologous recombinational repair. BRCA2 interacts with RAD51
      monomers, as well as nucleoprotein filaments, primarily though the conserved BRC
      motifs. The unrelated C-terminal region of BRCA2 also interacts with RAD51. Here
      we show that the BRCA2 C terminus interacts directly with RAD51 filaments, but
      not monomers, by binding an interface created by two adjacent RAD51 protomers.
      These interactions stabilize filaments so that they cannot be dissociated by
      association with BRC repeats. Interaction of the BRCA2 C terminus with the RAD51
      filament causes a large movement of the flexible RAD51 N-terminal domain that is
      important in regulating filament dynamics. We suggest that interactions of the
      BRCA2 C-terminal region with RAD51 may facilitate efficient nucleation of RAD51
      multimers on DNA and thereby stimulate recombination-mediated repair.

PMID- 17515905
TI  - The redox-switch domain of Hsp33 functions as dual stress sensor.
AB  - The redox-regulated chaperone Hsp33 is specifically activated upon exposure of
      cells to peroxide stress at elevated temperatures. Here we show that Hsp33
      harbors two interdependent stress-sensing regions located in the C-terminal redox
      switch domain of Hsp33: a zinc center sensing peroxide stress conditions and an
      adjacent linker region responding to unfolding conditions. Neither of these
      sensors works sufficiently in the absence of the other, making the simultaneous
      presence of both stress conditions a necessary requirement for Hsp33's full
      activation. Upon activation, Hsp33's redox-switch domain adopts a natively
      unfolded conformation, thereby exposing hydrophobic surfaces in its N-terminal
      substrate-binding domain. The specific activation of Hsp33 by the oxidative
      unfolding of its redox-switch domain makes this chaperone optimally suited to
      quickly respond to oxidative stress conditions that lead to protein unfolding.

PMID- 17515906
TI  - The antibiotic viomycin traps the ribosome in an intermediate state of
      translocation.
AB  - During protein synthesis, transfer RNA and messenger RNA undergo coupled
      translocation through the ribosome's A, P and E sites, a process catalyzed by
      elongation factor EF-G. Viomycin blocks translocation on bacterial ribosomes and
      is believed to bind at the subunit interface. Using fluorescent resonance energy
      transfer and chemical footprinting, we show that viomycin traps the ribosome in
      an intermediate state of translocation. Changes in FRET efficiency show that
      viomycin causes relative movement of the two ribosomal subunits indistinguishable
      from that induced by binding of EF-G with GDPNP. Chemical probing experiments
      indicate that viomycin induces formation of a hybrid-state translocation
      intermediate. Thus, viomycin inhibits translation through a unique mechanism,
      locking ribosomes in the hybrid state; the EF-G-induced 'ratcheted' state
      observed by cryo-EM is identical to the hybrid state; and, since translation is
      viomycin sensitive, the hybrid state may be present in vivo.

PMID- 17515907
TI  - Structural basis for the transforming activity of human cancer-related signaling
      adaptor protein CRK.
AB  - CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein
      CRK that regulate transcription and cytoskeletal reorganization for cell growth
      and motility by linking tyrosine kinases to small G proteins. CRKI shows
      substantial transforming activity, whereas the activity of CRKII is low, and
      phosphorylated CRKII has no biological activity whatsoever. The molecular
      mechanisms underlying the distinct biological activities of the CRK proteins
      remain elusive. We determined the solution structures of CRKI, CRKII and
      phosphorylated CRKII by NMR and identified the molecular mechanism that gives
      rise to their activities. Results from mutational analysis using rodent 3Y1
      fibroblasts were consistent with those from the structural studies. Together,
      these data suggest that the linker region modulates the binding of CRKII to its
      targets, thus regulating cell growth and motility.

PMID- 17515908
TI  - Engineering synthetic signaling proteins with ultrasensitive input/output
      control.
AB  - Many signaling proteins are built from simple, modular components, yet display
      highly complex signal-processing behavior. Here we explore how modular domains
      can be used to build an ultrasensitive switch--a nonlinear input/output function
      that is central to many complex biological behaviors. By systematically altering
      the number and affinity of modular autoinhibitory interactions, we show that we
      can predictably convert a simple linear signaling protein into an ultrasensitive
      switch.

PMID- 17515909
TI  - A universal RNAi-based logic evaluator that operates in mammalian cells.
AB  - Molecular automata that combine sensing, computation and actuation enable
      programmable manipulation of biological systems. We use RNA interference (RNAi)
      in human kidney cells to construct a molecular computing core that implements
      general Boolean logic to make decisions based on endogenous molecular inputs. The
      state of an endogenous input is encoded by the presence or absence of 'mediator'
      small interfering RNAs (siRNAs). The encoding rules, combined with a specific
      arrangement of the siRNA targets in a synthetic gene network, allow direct
      evaluation of any Boolean expression in standard forms using siRNAs and indirect
      evaluation using endogenous inputs. We demonstrate direct evaluation of
      expressions with up to five logic variables. Implementation of the encoding rules
      through sensory up- and down-regulatory links between the inputs and siRNA
      mediators will allow arbitrary Boolean decision-making using these inputs.

PMID- 17515910
TI  - Decoding global gene expression programs in liver cancer by noninvasive imaging.
AB  - Paralleling the diversity of genetic and protein activities, pathologic human
      tissues also exhibit diverse radiographic features. Here we show that dynamic
      imaging traits in non-invasive computed tomography (CT) systematically correlate
      with the global gene expression programs of primary human liver cancer.
      Combinations of twenty-eight imaging traits can reconstruct 78% of the global
      gene expression profiles, revealing cell proliferation, liver synthetic function,
      and patient prognosis. Thus, genomic activity of human liver cancers can be
      decoded by noninvasive imaging, thereby enabling noninvasive, serial and frequent
      molecular profiling for personalized medicine.

PMID- 17515911
TI  - The association between weight history and physical performance in the Health,
      Aging and Body Composition study.
AB  - OBJECTIVE: Although the association between current obesity and physical
      disability is well known, the cumulative effect of obesity is unknown. Using data
      from the Health, Aging and Body Composition study, we examined the association
      between weight history in young and middle adulthood and weight status in late
      adulthood with physical performance in late adulthood. DESIGN: Longitudinal
      cohort study. SUBJECTS: White and black men and women aged 70-79 years at study
      baseline (n=2803). MEASURES: Body mass index (BMI; kg/m(2)) was calculated using
      recalled height at age 25 and weight at age 25 and 50 and measured height and
      weight at ages 70-79. Physical performance at ages 70-79 was assessed using a
      short physical performance battery (SPPB) and a 400-m walk test. RESULTS: In this
      well-functioning cohort, approximately 24% of men and 8% of women reported being
      overweight or obese (BMI > or =25 kg/m(2)) at age 25, 51% of men and 37% of women
      reported being overweight or obese at age 50, and 69% of men and 66% of women
      were overweight or obese at ages 70-79. Men and women who were obese (BMI > or
      =30 kg/m(2)) at ages 25, 50 and 70-79 had significantly worse SPPB scores and 400
      m walk times than those who were normal weight. Women who were overweight (BMI 25
      29.9 kg/m(2)) at ages 25, 50 and 70-79 also had significantly worse physical
      performance. Furthermore, men and women who had a history of being overweight or
      obese at ages 25 or 50 had worse physical performance compared to those who were
      normal weight throughout or who were overweight or obese at ages 70-79 but not in
      midlife or earlier. CONCLUSIONS: Maintaining a healthy body weight throughout
      adulthood may play a role in preventing or delaying the onset of physical
      disability.

PMID- 17515912
TI  - School-based physical activity and changes in adiposity.
AB  - OBJECTIVE: School-based physical education (PE) is often proposed as a strategy
      for obesity prevention, but many trials have found non-significant effects on
      body mass index (BMI). We examined the impact of school PE on adiposity in
      adolescents, using an ecological analysis to relate the number of PE sessions to
      changes in BMI and waist circumference. RESEARCH METHODS AND PROCEDURES: Five
      year, longitudinal, school-based study involving 34 secondary schools in London,
      England. Students were aged 11-12 years at baseline. Twenty-five schools reported
      one weekly session of PE, seven schools reported two sessions and two boys'
      schools reported three sessions. Weights, heights and waist circumferences were
      measured annually, and complete data from the first and fifth years of the study
      were available on 2727 students. Analyses compared anthropometric changes between
      students in schools with higher or lower amounts of PE time. In boys, the
      comparisons were between those receiving 1, 2 or 3 weekly sessions. In girls,
      comparisons were between those receiving one and two sessions. RESULTS: There
      were no differences in BMI changes or the percentage of students classified as
      obese between schools of higher and lower frequency of PE. However, using
      unadjusted data, there were lower gains in waist circumference in boys and girls
      from the higher PE schools. Controlling for baseline demographic and
      anthropometric characteristics, boys in schools providing 3 weekly PE sessions
      gained on average approximately 3 cm less than boys in schools providing one or
      two sessions (P<0.001). Differences in girls were in the same direction but not
      significant. DISCUSSION: Higher levels of school PE were associated with lower
      gains in adiposity in boys. This strengthens the case for including
      recommendations on school PE time as part of population strategies to control
      adolescent obesity.

PMID- 17515913
TI  - Molecular mechanisms of diabetes reversibility after bariatric surgery.
AB  - OBJECTIVE: Insulin resistance is a strong biological marker of both obesity and
      type 2 diabetes. Abnormal fat deposition within skeletal muscle has been
      identified as a mechanism of obesity-associated insulin resistance.
      Biliopancreatic diversion (BPD), inducing a massive lipid malabsorption, leads to
      a reversion of type 2 diabetes. To elucidate the mechanisms of diabetes
      reversibility, the expression of genes involved in glucose and free fatty acids
      (FFAs) metabolism was investigated in skeletal muscle biopsies from obese, type 2
      diabetic subjects. Peripheral insulin sensitivity and insulin secretion was also
      measured. SUBJECTS: Eight Caucasian obese diabetic patients (BMI 52.1+/-1.85
      kg/m(2)) were studied before and 3 years after BPD. MEASUREMENTS: The mRNA levels
      were estimated by quantitative real-time reverse transcription polymerase chain
      reaction (RT-PCR), insulin sensitivity by the euglycemic-hyperinsulinemic clamp
      and insulin secretion using a model describing the relationship between insulin
      secretion and glucose concentration. RESULTS: Whole-body glucose uptake (M),
      normalized by fat-free mass, significantly increased in post-obese subjects
      (P<0.0001). Total insulin output decreased (P<0.05) in association with a
      significant improvement of beta-cells glucose sensitivity (P<0.05). mRNA levels
      of FABP3 (P<0.05), FACL (P<0.05), ACC2 (P<0.05), HKII (P<0.05) and PDK4 (P<0.05)
      were significantly decreased, while SREBP1c mRNA increased (P<0.05) after BPD.
      CONCLUSION: Reversibility of type 2 diabetes after BPD is dependent on the
      improvement of skeletal muscle insulin sensitivity, mediated by changes in the
      expression of genes regulating glucose and fatty acid metabolism in response to
      nutrient availability.

PMID- 17515914
TI  - Enhanced ethanol production inside carbon-nanotube reactors containing catalytic
      particles.
AB  - Carbon nanotubes (CNTs) have well-defined hollow interiors and exhibit unusual
      mechanical and thermal stability as well as electron conductivity. This opens
      intriguing possibilities to introduce other matter into the cavities, which may
      lead to nanocomposite materials with interesting properties or behaviour
      different from the bulk. Here, we report a striking enhancement of the catalytic
      activity of Rh particles confined inside nanotubes for the conversion of CO and
      H2 to ethanol. The overall formation rate of ethanol (30.0 mol mol(-1)Rh h(-1))
      inside the nanotubes exceeds that on the outside of the nanotubes by more than an
      order of magnitude, although the latter is much more accessible. Such an effect
      with synergetic confinement has not been observed before in catalysis involving
      CNTs. We believe that our discovery may be of a quite general nature and could
      apply to many other processes. It is anticipated that this will motivate
      theoretical and experimental studies to further the fundamental understanding of
      the host-guest interaction within carbon and other nanotube systems.

PMID- 17515915
TI  - Modulus-density scaling behaviour and framework architecture of nanoporous self
      assembled silicas.
AB  - Natural porous materials such as bone, wood and pith evolved to maximize modulus
      for a given density. For these three-dimensional cellular solids, modulus scales
      quadratically with relative density. But can nanostructuring improve on Nature's
      designs? Here, we report modulus-density scaling relationships for cubic (C),
      hexagonal (H) and worm-like disordered (D) nanoporous silicas prepared by
      surfactant-directed self-assembly. Over the relative density range, 0.5 to 0.65,
      Young's modulus scales as (density)n where n(C)<n(H)<n(D)<2, indicating that
      nanostructured porous silicas exhibit a structure-specific hierarchy of modulus
      values D<H<C. Scaling exponents less than 2 emphasize that the moduli are less
      sensitive to porosity than those of natural cellular solids, which possess
      extremal moduli based on linear elasticity theory. Using molecular modelling and
      Raman and NMR spectroscopy, we show that uniform nanoscale confinement causes the
      silica framework of self-assembled silica to contain a higher portion of small,
      stiff rings than found in other forms of amorphous silica. The nanostructure
      specific hierarchy and systematic increase in framework modulus we observe, when
      decreasing the silica framework thickness below 2 nm, provides a new ability to
      maximize mechanical properties at a given density needed for nanoporous materials
      integration.

PMID- 17515916
TI  - Hierarchical architectures by synergy between dynamical template self-assembly
      and biomineralization.
AB  - Diatoms, shells, bones and teeth are exquisite examples of well-defined
      structures, arranged from nanometre to macroscopic length scale, produced by
      natural biomineralization using organic templates to control the growth of the
      inorganic phase. Although strategies mimicking Nature have partially succeeded in
      synthesizing human-designed bio-inorganic composite materials, our limited
      understanding of fundamental mechanisms has so far kept the level of hierarchical
      complexity found in biological organisms out of the chemists' reach. In this
      letter, we report on the synthesis of unprecedented double-walled silica
      nanotubes with monodisperse diameters that self-organize into highly ordered
      centimetre-sized fibres. A unique synergistic growth mechanism is elucidated by
      the combination of light and electron microscopy, synchrotron X-ray diffuse
      scattering and Raman spectroscopy. Following this growth mechanism, macroscopic
      bundles of nanotubules result from the kinetic cross-coupling of two molecular
      processes: a dynamical supramolecular self-assembly and a stabilizing silica
      mineralization. The feedback actions between the template growth and the
      inorganic deposition are driven by a mutual electrostatic neutralization. This
      'dynamical template' concept can be further generalized as a rational preparation
      scheme for materials with well-defined multiscale architectures and also as a
      fundamental mechanism for growth processes in biological systems.

PMID- 17515917
TI  - Nanoscale heterogeneity promotes energy dissipation in bone.
AB  - Nanomechanical heterogeneity is expected to influence elasticity, damage,
      fracture and remodelling of bone. Here, the spatial distribution of
      nanomechanical properties of bone is quantified at the length scale of individual
      collagen fibrils. Our results show elaborate patterns of stiffness ranging from
      approximately 2 to 30 GPa, which do not correlate directly with topographical
      features and hence are attributed to underlying local structural and
      compositional variations. We propose a new energy-dissipation mechanism arising
      from nanomechanical heterogeneity, which offers a means for ductility
      enhancement, damage evolution and toughening. This hypothesis is supported by
      computational simulations that incorporate the nanoscale experimental results.
      These simulations predict that non-uniform inelastic deformation over larger
      areas and increased energy dissipation arising from nanoscale heterogeneity lead
      to markedly different biomechanical properties compared with a uniform material.
      The fundamental concepts discovered here are applicable to a broad class of
      biological materials and may serve as a design consideration for biologically
      inspired materials technologies.

PMID- 17515918
TI  - Origin and control of high-temperature ferromagnetism in semiconductors.
AB  - The extensive experimental and computational search for multifunctional materials
      has resulted in the development of semiconductor and oxide systems, such as
      (Ga,Mn)N, (Zn,Cr)Te and HfO(2), which exhibit surprisingly stable ferromagnetic
      signatures despite having a small or nominally zero concentration of magnetic
      elements. Here, we show that the ferromagnetism of (Zn,Cr)Te, and the associated
      magnetooptical and magnetotransport functionalities, are dominated by the
      formation of Cr-rich (Zn,Cr)Te metallic nanocrystals embedded in the Cr-poor
      (Zn,Cr)Te matrix. Importantly, the formation of these nanocrystals can be
      controlled by manipulating the charge state of the Cr ions during the epitaxy.
      The findings provide insight into the origin of ferromagnetism in a broad range
      of semiconductors and oxides, and indicate possible functionalities of these
      composite systems. Furthermore, they demonstrate a bottom-up method for self
      organized nanostructure fabrication that is applicable to any system in which the
      charge state of a constituent depends on the Fermi-level position in the host
      semiconductor.

PMID- 17515919
TI  - Macrophage-specific PPARgamma controls alternative activation and improves
      insulin resistance.
AB  - Obesity and insulin resistance, the cardinal features of metabolic syndrome, are
      closely associated with a state of low-grade inflammation. In adipose tissue
      chronic overnutrition leads to macrophage infiltration, resulting in local
      inflammation that potentiates insulin resistance. For instance, transgenic
      expression of Mcp1 (also known as chemokine ligand 2, Ccl2) in adipose tissue
      increases macrophage infiltration, inflammation and insulin resistance.
      Conversely, disruption of Mcp1 or its receptor Ccr2 impairs migration of
      macrophages into adipose tissue, thereby lowering adipose tissue inflammation and
      improving insulin sensitivity. These findings together suggest a correlation
      between macrophage content in adipose tissue and insulin resistance. However,
      resident macrophages in tissues display tremendous heterogeneity in their
      activities and functions, primarily reflecting their local metabolic and immune
      microenvironment. While Mcp1 directs recruitment of pro-inflammatory classically
      activated macrophages to sites of tissue damage, resident macrophages, such as
      those present in the adipose tissue of lean mice, display the alternatively
      activated phenotype. Despite their higher capacity to repair tissue, the precise
      role of alternatively activated macrophages in obesity-induced insulin resistance
      remains unknown. Using mice with macrophage-specific deletion of the peroxisome
      proliferator activated receptor-gamma (PPARgamma), we show here that PPARgamma is
      required for maturation of alternatively activated macrophages. Disruption of
      PPARgamma in myeloid cells impairs alternative macrophage activation, and
      predisposes these animals to development of diet-induced obesity, insulin
      resistance, and glucose intolerance. Furthermore, gene expression profiling
      revealed that downregulation of oxidative phosphorylation gene expression in
      skeletal muscle and liver leads to decreased insulin sensitivity in these
      tissues. Together, our findings suggest that resident alternatively activated
      macrophages have a beneficial role in regulating nutrient homeostasis and suggest
      that macrophage polarization towards the alternative state might be a useful
      strategy for treating type 2 diabetes.

PMID- 17515920
TI  - Chromosomally unstable mouse tumours have genomic alterations similar to diverse
      human cancers.
AB  - Highly rearranged and mutated cancer genomes present major challenges in the
      identification of pathogenetic events driving the neoplastic transformation
      process. Here we engineered lymphoma-prone mice with chromosomal instability to
      assess the usefulness of mouse models in cancer gene discovery and the extent of
      cross-species overlap in cancer-associated copy number aberrations. Along with
      targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and
      PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute
      lymphoblastic leukaemia/lymphoma (T-ALL). The murine cancers acquire widespread
      recurrent amplifications and deletions targeting loci syntenic to those not only
      in human T-ALL but also in diverse human haematopoietic, mesenchymal and
      epithelial tumours. These results indicate that murine and human tumours
      experience common biological processes driven by orthologous genetic events in
      their malignant evolution. The highly concordant nature of genomic events
      encourages the use of genomically unstable murine cancer models in the discovery
      of biological driver events in the human oncogenome.

PMID- 17515921
TI  - Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange
      factors.
AB  - Eukaryotic cells mobilize the actin cytoskeleton to generate a remarkable
      diversity of morphological behaviours, including motility, phagocytosis and
      cytokinesis. Much of this diversity is mediated by guanine nucleotide exchange
      factors (GEFs) that activate Rho family GTPases-the master regulators of the
      actin cytoskeleton. There are over 80 Rho GEFs in the human genome (compared to
      only 22 genes for the Rho GTPases themselves), and the evolution of new and
      diverse GEFs is thought to provide a mechanism for linking the core cytoskeletal
      machinery to a wide range of new control inputs. Here we test this hypothesis and
      ask if we can systematically reprogramme cellular morphology by engineering
      synthetic GEF proteins. We focused on Dbl family Rho GEFs, which have a highly
      modular structure common to many signalling proteins: they contain a catalytic
      Dbl homology (DH) domain linked to diverse regulatory domains, many of which
      autoinhibit GEF activity. Here we show that by recombining catalytic GEF domains
      with new regulatory modules, we can generate synthetic GEFs that are activated by
      non-native inputs. We have used these synthetic GEFs to reprogramme cellular
      behaviour in diverse ways. The GEFs can be used to link specific cytoskeletal
      responses to normally unrelated upstream signalling pathways. In addition,
      multiple synthetic GEFs can be linked as components in series to form an
      artificial cascade with improved signal processing behaviour. These results show
      the high degree of evolutionary plasticity of this important family of modular
      signalling proteins, and indicate that it may be possible to use synthetic
      biology approaches to manipulate the complex spatio-temporal control of cell
      morphology.

PMID- 17515923
TI  - Top-down versus bottom-up-rediscovering physiology via systems biology?

PMID- 17515922
TI  - A top-down systems biology view of microbiome-mammalian metabolic interactions in
      a mouse model.
AB  - Symbiotic gut microorganisms (microbiome) interact closely with the mammalian
      host's metabolism and are important determinants of human health. Here, we
      decipher the complex metabolic effects of microbial manipulation, by comparing
      germfree mice colonized by a human baby flora (HBF) or a normal flora to
      conventional mice. We perform parallel microbiological profiling, metabolic
      profiling by (1)H nuclear magnetic resonance of liver, plasma, urine and ileal
      flushes, and targeted profiling of bile acids by ultra performance liquid
      chromatography-mass spectrometry and short-chain fatty acids in cecum by GC-FID.
      Top-down multivariate analysis of metabolic profiles reveals a significant
      association of specific metabotypes with the resident microbiome. We derive a
      transgenomic graph model showing that HBF flora has a remarkably simple
      microbiome/metabolome correlation network, impacting directly on the host's
      ability to metabolize lipids: HBF mice present higher ileal concentrations of
      tauro-conjugated bile acids, reduced plasma levels of lipoproteins but higher
      hepatic triglyceride content associated with depletion of glutathione. These data
      indicate that the microbiome modulates absorption, storage and the energy harvest
      from the diet at the systems level.

PMID- 17515929
TI  - Detection and quantification of IgM(+) lymphocytes in fetal lamb spleen, liver
      and lymph nodes by flow cytometry.
AB  - The first stage in Peyer's patch development in the fetal lamb is characterized
      by the colonization of the rudimentary Peyer's patches by precursor cells
      expressing the IgM surface receptor. In the fetal lamb, the spleen has been
      implicated as the source of gene-rearranged IgM(+) B lymphocytes. This study was
      intended to quantitate IgM(+) lymphocytes in the spleen, lymph nodes and liver of
      fetal lambs at various gestational ages between 63 and 110 days using flow
      cytometry. Flow-cytometric analysis revealed that IgM(+) lymphocytes were rare in
      the liver being consistently less than 1% at every gestational age examined.
      IgM(+) lymphocytes were detected in the spleen (mean 9.18%) and prescapular lymph
      nodes (mean 11.89%) as early as 63 days. In both spleen and lymph nodes, the
      highest representation of IgM(+) lymphocytes occurred between 70 and 86 days
      gestation. The highest mean percentage of IgM(+) lymphocytes was observed in the
      spleen (22.63%) and lymph nodes (17.02%) at 75 days gestation. From 98 days
      onwards, B-lymphocyte density gradually decreased in both spleen and prescapular
      lymph nodes. This study indicates that substantial populations of IgM(+)
      lymphocytes were present in both the spleen and prescapular lymph nodes from 70
      days gestation and implies that both of these locations could be potential
      sources for the normal colonization of the ileal Peyer's patches.

PMID- 17515930
TI  - Rad3-dependent phosphorylation of the checkpoint clamp regulates repair-pathway
      choice.
AB  - When replication forks collapse, Rad3 phosphorylates the checkpoint-clamp protein
      Rad9 in a manner that depends on Thr 225, a residue within the PCNA-like domain.
      The physiological function of Thr 225-dependent Rad9 phosphorylation, however,
      remains elusive. Here, we show that Thr 225-dependent Rad9 phosphorylation by
      Rad3 regulates DNA repair pathways. A rad9(T225C) mutant induces a translesion
      synthesis (TLS)-dependent high spontaneous mutation rate and a hyper
      recombination phenotype. Consistent with this, Rad9 coprecipitates with the post
      replication repair protein Mms2. This interaction is dependent on Rad9 Thr 225
      and is enhanced by DNA damage. Genetic analyses indicate that Thr 225-dependent
      Rad9 phosphorylation prevents inappropriate Rhp51-dependent recombination,
      potentially by redirecting the repair through a Pli1-mediated sumoylation pathway
      into the error-free branch of the Rhp6 repair pathway. Our findings reveal a new
      mechanism by which phosphorylation of Rad9 at Thr 225 regulates the choice of
      repair pathways for maintaining genomic integrity during the cell cycle.

PMID- 17515931
TI  - Caspase-14 protects against epidermal UVB photodamage and water loss.
AB  - Caspase-14 belongs to a conserved family of aspartate-specific proteinases. Its
      expression is restricted almost exclusively to the suprabasal layers of the
      epidermis and the hair follicles. Moreover, the proteolytic activation of caspase
      14 is associated with stratum corneum formation, implicating caspase-14 in
      terminal keratinocyte differentiation and cornification. Here, we show that the
      skin of caspase-14-deficient mice was shiny and lichenified, indicating an
      altered stratum-corneum composition. Caspase-14-deficient epidermis contained
      significantly more alveolar keratohyalin F-granules, the profilaggrin stores.
      Accordingly, caspase-14-deficient epidermis is characterized by an altered
      profilaggrin processing pattern and we show that recombinant caspase-14 can
      directly cleave profilaggrin in vitro. Caspase-14-deficient epidermis is
      characterized by reduced skin-hydration levels and increased water loss. In view
      of the important role of filaggrin in the structure and moisturization of the
      skin, the knockout phenotype could be explained by an aberrant processing of
      filaggrin. Importantly, the skin of caspase-14-deficient mice was highly
      sensitive to the formation of cyclobutane pyrimidine dimers after UVB
      irradiation, leading to increased levels of UVB-induced apoptosis. Removal of the
      stratum corneum indicate that caspase-14 controls the UVB scavenging capacity of
      the stratum corneum.

PMID- 17515932
TI  - Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse
      embryonic stem cells.
AB  - The pluripotency of embryonic stem (ES) cells is thought to be maintained by a
      few key transcription factors, including Oct3/4 and Sox2. The function of Oct3/4
      in ES cells has been extensively characterized, but that of Sox2 has yet to be
      determined. Sox2 can act synergistically with Oct3/4 in vitro to activate Oct-Sox
      enhancers, which regulate the expression of pluripotent stem cell-specific genes,
      including Nanog, Oct3/4 and Sox2 itself. These findings suggest that Sox2 is
      required by ES cells for its Oct-Sox enhancer activity. Using inducible Sox2-null
      mouse ES cells, we show that Sox2 is dispensable for the activation of these Oct
      Sox enhancers. In contrast, we demonstrate that Sox2 is necessary for regulating
      multiple transcription factors that affect Oct3/4 expression and that the forced
      expression of Oct3/4 rescues the pluripotency of Sox2-null ES cells. These
      results indicate that the essential function of Sox2 is to stabilize ES cells in
      a pluripotent state by maintaining the requisite level of Oct3/4 expression.

PMID- 17515933
TI  - Insidious progression of paraparesis secondary to type III spinal meningeal cyst:
      a study of six difficult cases.
AB  - STUDY DESIGN: Case report. SETTING: Neuro-orthopaedic Unit, Fukui University
      Hospital, Japan. CASE REPORT: We studied six patients with insidious progression
      of paraparesis caused by thoracic and thoracolumbar spine type III spinal
      meningeal cyst and intradural arachnoid cyst, who underwent microsurgical
      decompression. Histologically, some samples showed oedematous and hypertrophic
      changes of the arachnoidal tissue together with occasional tophaceous deposits
      and calcification. Surgical treatment was complete excision of the cyst, or wide
      fenestration of these membrane, and close a communicating fistula, if detectable.
      All patients improved neurologically after microscopic surgery. CONCLUSION: We
      stress the significance of neuroimaging and neurological assessment in patients
      with gradual progression of paraparesis caused by intradural arachnoid cyst, but
      surgical procedure and timing of operative intervention require further
      considerations.

PMID- 17515934
TI  - Fees in primary care.

PMID- 17515935
TI  - Hip fracture management in New Zealand--we need to do better.

PMID- 17515936
TI  - Brainstem lesions presenting with nausea and vomiting.
AB  - Positional vomiting is an important alerting sign for the presence of a brainstem
      central nervous system (CNS) lesion. Failure to identify another cause of
      protracted vomiting should prompt consideration of a CNS cause.

PMID- 17515937
TI  - Folic acid and neural tube defects in New Zealand: a cautionary tale?

PMID- 17515938
TI  - Medical image. Arthritis and macroglossia. Multiple myeloma complicated by
      amyloidosis causing arthropathy.

PMID- 17515939
TI  - Older patients with hip fractures: evaluation of a long-term specialist
      orthopaedic medicine service in their outcomes.
AB  - AIMS: To evaluate the long-term outcomes of a specialist orthopaedic medicine
      service in older patients up to 12 months after hip fracture. METHODS: All
      patients over the age of 65 years admitted with hip fracture under the shared
      care of geriatricians and orthopaedic surgeons over a 6-month period were
      identified in an initial audit. A follow-up postal questionnaire was sent to
      those patients asking about their place of domicile, level of functioning,
      compliance with osteoporosis treatment, and whether they had sustained further
      fractures in the 12 months following discharge from hospital. Mortality was also
      recorded. RESULTS: The 1-year mortality of the 149 patients discharged from
      hospital following their hip fracture (who were identified in the initial audit)
      was 18.8%. There were 69 (46.3%) responses to the questionnaire. The mean age of
      respondents was 81.3 years (range 66-98 years). At discharge, only 5 of 69 (7.2%)
      patients were independent in their walking, 13 (18.8%) walked with the aid of a
      stick, 39 (56.5%) with a frame, 7 (10.1%) required supervision, and 5 (7.2%) were
      immobile. Excluding those who were immobile prior to their hip fracture, 31 of 64
      (48.4%) of patients regained their pre-morbid level of mobility at 12 months. At
      discharge, 27 of 69 (39.1%) patients were independent with activities of
      showering, dressing, and toileting--with 42 of 64 (65.6%) independent at 12
      months. At discharge, 57 of 69 (82.6%) patients were on calcium and vitamin D,
      and 5 (7.2%) on alendronate. At 12 months, 50 of 64 (78.1%) remained on calcium,
      40 (62.5%) on vitamin D, and 26 (40.6%) on alendronate. Five of 64 (7.8%)
      patients experienced a total of 11 further osteoporotic fractures at 12 months,
      but no further hip fractures. Of respondents discharged home, 44 of 50 (88%)
      remained at home at 12 months. CONCLUSIONS: Shared care between geriatricians and
      orthopaedic surgeons for older hip fracture patients appears to be associated
      with a reduced 1-year mortality, improved treatment of osteoporosis, and return
      to home. Many patients, however, continue to have impaired function and mobility.

PMID- 17515940
TI  - Exploring general practitioner identification and management of psychosocial
      Yellow Flags in acute low back pain.
AB  - AIM: Over the past decade, psychosocial issues have been increasingly identified
      as risk factors that are associated with the development of chronicity and
      disability. These psychosocial risk factors are known as Yellow Flags. In New
      Zealand, in 1997, the Accident Compensation Corporation (ACC) published the Acute
      Low Back Pain Guide and the Guide to Assessing Psychosocial Yellow Flags in Acute
      Low Back Pain. The aim of this qualitative study is to understand the experiences
      of general practitioners (GPs) in the identification and management of
      psychosocial Yellow Flags in patients with acute low back pain. METHOD: A
      qualitative research approach was used. GPs were purposively selected and semi
      structured interviews were undertaken. RESULTS: The doctor-patient relationship
      created the key element for the GPs in approaching any psychosocial factors that
      were identified. The management of psychosocial factors depended on an individual
      GP's worldview and orientation to the biopsychosocial model of pain. Problems
      with time management were composed of multifactorial facets. Funding, lack of
      appropriate training, and the GPs' perception of ACC's rehabilitation model, all
      formed components of the meanings that the GPs constructed from their
      experiences. CONCLUSION: GPs did not use the Guide to Assessing Psychosocial
      Yellow Flags in Acute Low Back Pain or the screening questionnaire to identify
      psychosocial risk factors in their patients with low back pain. Investment of
      resources in GPs is needed to empower them to be effective gatekeepers guarding
      against chronicity. This demonstrates a need to alter the current ACC Guideline
      dissemination and implementation.

PMID- 17515941
TI  - Management of scleroderma in a New Zealand tertiary rheumatology centre: emphasis
      on pulmonary complications.
AB  - AIMS: To determine the current local practice of managing scleroderma (SSc)
      patients, in particular screening of SSc-related lung disease in a tertiary
      rheumatology centre. METHODS: SSc patients were identified from our inpatient
      (July 1999 till June 2004) and outpatient (January 2002 till June 2004)
      databases. Patient demographics and relevant investigations performed to monitor
      for pulmonary, renal, and cardiac complications related to SSc were sought from
      computerised clinical and laboratory records. RESULTS: Nine of the 39 (23%)
      limited SSc (lcSSc) patients and 5 of the 10 (50%) diffuse SSc (dcSSc) patients
      had lung involvement. A higher proportion of diffuse SSc patients had
      investigations for SSc lung disease compared to the lcSSc group (90% vs 67% had
      pulmonary function tests and 70% vs 56% had high resolution chest CT scans
      respectively). About half of the patients in both groups had echocardiographs
      (50% lcSSc vs 46% dcSSc) for assessment of pulmonary arterial hypertension.
      CONCLUSION: SSc lung disease has been generally poorly screened in our cohort of
      patients with SSc. Limited SSc patients were not screened as rigorously as dcSSc
      patients for SSc lung disease. In large part, this was because of the lack of
      availability of treatments in New Zealand when the lung disease was identified.
      The generation of a standardised screening and monitoring protocol may help
      identify patients with progressive lung disease so that early treatment could be
      considered as this becomes more readily available.

PMID- 17515942
TI  - Practitioners, patients, and their visits: a description of accident and medical
      (A&M) clinics in New Zealand, 2001/2.
AB  - AIMS: The National Primary Medical Care survey was undertaken to describe primary
      health care in New Zealand, including the characteristics of accident and medical
      (A and M) clinic providers, their practices, the patients they see, the problems
      presented, and the management offered. METHODS: Data were collected from a 50%
      random sample of all A and M clinics in New Zealand as part of the National
      Primary Medical Care survey carried out in 2001/2. RESULTS: Data were obtained
      from 12 A and M clinics throughout New Zealand between usual hours (Monday-Friday
      8 am-6 pm) and at other times. A and M clinics were staffed by an average of 2.7
      full-time equivalent (FTE) A and M practitioners . Most clinics operated as a
      limited liability company. The majority of A and M practitioners were male and
      aged between 35-44 years. On average, A and M doctors had been in practice for
      over 10 years and had been in the sampled practice for only 2.9 years. More than
      a third of doctors had not trained in New Zealand. The doctors worked, on
      average, 6.3 half days and saw nearly 90 patients per week. The findings suggest
      that young patients and a diverse ethnic range attend A and M practices.
      Community Services Card holders were not usual patients. Few patients had an
      ongoing relationship with the practices. Most visits related to a single, new,
      and short-term problem that was often an injury or a respiratory illness. About a
      fifth of visits were associated with an order for an investigation or an X-ray,
      fewer investigations were arranged outside usual hours. About half the visits
      resulted in a prescription but more visits outside normal hours received
      pharmacological treatment and the number of items was higher. The most frequently
      prescribed items were antibiotics and analgesics. Follow-up was arranged for
      between a third to a half of visits, depending on the time of day. Referrals were
      often made to non-medical destinations. While patient and visit characteristics
      were generally similar regardless of whether the visit occurred during usual
      working hours or at other times, some differences were apparent in the type of
      problems that were presented out of hours and their management. CONCLUSIONS: The
      main impression is that the medical A and M clinics provide episodic treatment
      for relatively young patients mainly related to a new, short-term problem,
      particularly an injury or a respiratory illness. This picture is consistent with
      previous research and the role of similar clinics overseas. Further work is
      needed to compare A and M clinics with established general practice in relation
      to the services that are provided as well as the acceptability and quality of
      these services.

PMID- 17515943
TI  - General practice fees review committees.

PMID- 17515944
TI  - Fees reviews of New Zealand general practices--a New Zealand Medical Association
      (NZMA) perspective.

PMID- 17515945
TI  - Rat-bite fever: a cautionary tale.
AB  - We present the first ever report of streptobacillary rat-bite fever in New
      Zealand. The patient was a young man who was admitted with systemic sepsis. He
      presented with a high fever, hypotension, and tender axillary lymphadenopathy. He
      had been bitten by a rat a week earlier. Blood cultures grew Streptobacillus
      moniliformis, thus confirming the diagnosis. The literature on rat-bite fever is
      also reviewed.

PMID- 17515946
TI  - Why is there a decreasing retention of New Zealand junior doctors?

PMID- 17515947
TI  - PAI-1 is a Critical Upstream Regulator of the TGF-beta1/EGF-Induced Invasive
      Phenotype in Mutant p53 Human Cutaneous Squamous Cell Carcinoma.
AB  - The emergence of highly aggressive subtypes of human cutaneous squamous cell
      carcinoma (SCC) often reflects increased autocrine/paracrine TGF-beta synthesis
      and epidermal growth factor receptor (EGFR) amplification. Cooperative TGF
      beta/EGFR signaling promotes cell migration and induces expression of both
      proteases and protease inhibitors that regulate stromal remodeling resulting in
      acquisition of an invasive phenotype. TGF-beta1+EGF stimulation increases the
      production of several matrix metalloproteinases (MMPs) in human SCC. Among the
      most prominent is MMP-10 which is known to be elevated in SCC in situ. Activation
      of stromal plasminogen appears to be critical in triggering downstream MMP
      activity. Paradoxically, PAI-1, the major physiological inhibitor of plasmin
      generation, is also up-regulated under these conditions and is an early event in
      progression of incipient epidermal SCC. A model is proposed in which TGF
      beta1+EGF-dependent MMP-10 elevation directs focalized matrix remodeling events
      that promote epithelial cell plasticity and tissue invasion. Increased PAI-1
      expression serves to temporally and spatially modulate plasmin-initiated
      pericellular proteolysis, further facilitating epithelial invasive potential.
      Defining the complex signaling mechanisms that maintain this elegant balance is
      critical to developing potential therapeutics for the treatment of human
      cutaneous malignancies.

PMID- 17515948
TI  - How temporal cues can aid colour constancy.
AB  - Colour constancy assessed by asymmetric simultaneous colour matching usually
      reveals limited levels of performance in the unadapted eye. Yet observers can
      readily discriminate illuminant changes on a scene from changes in the spectral
      reflectances of the surfaces making up the scene. This ability is probably based
      on judgements of relational colour constancy, in turn based on the physical
      stability of spatial ratios of cone excitations under illuminant changes.
      Evidence is presented suggesting that the ability to detect violations in
      relational colour constancy depends on temporal transient cues. Because colour
      constancy and relational colour constancy are closely connected, it should be
      possible to improve estimates of colour constancy by introducing similar
      transient cues into the matching task. To test this hypothesis, an experiment was
      performed in which observers made surface-colour matches between patterns
      presented in the same position in an alternating sequence with period 2 s or, as
      a control, presented simultaneously, side-by-side. The degree of constancy was
      significantly higher for sequential presentation, reaching 87% for matches
      averaged over 20 observers. Temporal cues may offer a useful source of
      information for making colour-constancy judgements.

PMID- 17515949
TI  - Older adults in the division of domestic labor in communities on the outskirts of
      Beirut.
AB  - The gendered division of domestic labor has been widely studied over the last
      three decades. However, older adults' contribution to housework, especially in
      patriarchal communities in the Middle East, has been largely overlooked. This
      article examined the participation of older members of the household in domestic
      labor in three communities in the outskirts of Beirut, the capital of Lebanon.
      Drawing on a sample of 2,797 households, the results revealed that three salient
      factors seemed to have the major impact on older adults' participation in
      domestic labor; these were the presence of adult women (18-59 years old) in the
      household, the marital status and age of older adults. Older men's participation
      in domestic labor was much lower than that of older women, suggesting that a
      gender divide exists among older adults in the patriarchal setting of the study.
      Housework remains feminized in the later stage of life.

PMID- 17515950
TI  - Resting tension affects eNOS activity in a calcium-dependent way in airways.
AB  - The alteration of resting tension (RT) from 0.5 g to 2.5 g increased
      significantly airway smooth muscle contractions induced by acetylcholine (ACh) in
      rabbit trachea. The decrease in extracellular calcium concentration [Ca2+]o from
      2 mM to 0.2 mM reduced ACh-induced contractions only at 2.5 g RT with no effect
      at 0.5 g RT. The nonselective inhibitor of nitric oxide synthase (NOS), N(G)
      nitro-L-arginine methyl ester (L-NAME) increased ACh-induced contractions at 2.5
      g RT. The inhibitor of inducible NOS, S-methylsothiourea or neuronal NOS, 7
      nitroindazole had no effect. At 2.5 g RT, the reduction of [Ca2+]o from 2 mM to
      0.2 mM abolished the effect of L-NAME on ACh-induced contractions. The NO
      precursor L-arginine or the tyrosine kinase inhibitors erbstatin A and genistein
      had no effect on ACh-induced contractions obtained at 2.5 g RT. Our results
      suggest that in airways, RT affects ACh-induced contractions by modulating the
      activity of epithelial NOS in a calcium-dependent, tyrosine-phosphorylation
      independent way.

PMID- 17515951
TI  - Expression of selected integrins and selectins in bullous pemphigoid.
AB  - Blister development in bullous pemphigoid (BP) results from destruction of
      hemidesmosomes and basement membrane components within the dermoepidermal
      junction by autoantibodies. Adhesion molecules can take part in pathogenesis of
      this disease. The aim of the study was to determine the localization and
      expression of L- and E-selectins and beta1, beta3, and beta4 integrins by
      immunohistochemistry in skin lesions of 21 patients with BP, compared with 10
      healthy subjects. Expression of L and E selectins and beta1, beta3 integrins was
      detected mainly in basal keratinocytes and in inflammatory infiltrates in the
      dermis, expression of beta4 integrin was irregular and was detected mainly in
      dermal part of the blister, while in the control group only weak and single
      expression of the examined molecules was detected in basal keratinocytes and
      endothelium cells. The obtained results reveal the important role of selected
      selectins and integrins in development of skin lesions in BP.

PMID- 17515952
TI  - Gene expression in temporal lobe epilepsy is consistent with increased release of
      glutamate by astrocytes.
AB  - Patients with temporal lobe epilepsy (TLE) often have a shrunken hippocampus that
      is known to be the location in which seizures originate. The role of the
      sclerotic hippocampus in the causation and maintenance of seizures in temporal
      lobe epilepsy (TLE) has remained incompletely understood despite extensive
      neuropathological investigations of this substrate. To gain new insights and
      develop new testable hypotheses on the role of sclerosis in the pathophysiology
      of TLE, the differential gene expression profile was studied. To this end, DNA
      microarray analysis was used to compare gene expression profiles in sclerotic and
      non-sclerotic hippocampi surgically removed from TLE patients. Sclerotic
      hippocampi had transcriptional signatures that were different from non-sclerotic
      hippocampi. The differentially expressed gene set in sclerotic hippocampi
      revealed changes in several molecular signaling pathways, which included the
      increased expression of genes associated with astrocyte structure (glial
      fibrillary acidic protein, ezrin-moesin-radixin, palladin), calcium regulation
      (S100 calcium binding protein beta, chemokine (C-X-C motif) receptor 4) and blood
      brain barrier function (Aquaaporin 4, Chemokine (C-C- motif) ligand 2, Chemokine
      (C-C- motif) ligand 3, Plectin 1, intermediate filament binding protein 55kDa)
      and inflammatory responses. Immunohistochemical localization studies show that
      there is altered distribution of the gene-associated proteins in astrocytes from
      sclerotic foci compared with non-sclerotic foci. It is hypothesized that the
      astrocytes in sclerotic tissue have activated molecular pathways that could lead
      to enhanced release of glutamate by these cells. Such glutamate release may
      excite surrounding neurons and elicit seizure activity.

PMID- 17515953
TI  - Inhibition by tyroserleutide (YSL) on the invasion and adhesion of the mouse
      melanoma cell.
AB  - Tyroserleutide (YSL) is an active, low-molecular-weight polypeptide, comprised of
      three amino acids, that has shown antitumor effects on human hepatocarcinoma BEL
      7402 in vitro and in vivo. In this study, we evaluated the inhibition of YSL on
      invasion and adhesion of the mouse B16-F10 melanoma cell line by injecting B16
      F10 cells into the tail veins of C57BL/6 mice to establish an experimental lung
      metastasis model. YSL inhibited B16-F10 cell metastasis to lung, reducing the
      number and area of metastasis lesions. When we treated B16-F10 cells with YSL
      (0.01, 0.1, 1, 10, or 100 microg/mL) in vitro, we found that YSL inhibited the
      proliferation of B16-F10 cells with a 28.11% rate of inhibition. YSL
      significantly decreased the adhesiveness of B16-F10 cells to Matrigel with a
      29.15% inhibition rate; YSL also significantly inhibited the invasion of B16-F10
      cells, producing an inhibition of 35.31%. By analyses with Western blot and real
      time RT-PCR, we found that YSL markedly inhibited the expression of ICAM-1 in B16
      F10 cells. These data suggest that YSL inhibits the growth, invasion, and
      adhesion of B16-F10 cells.

PMID- 17515954
TI  - Blue laser light increases perfusion of a skin flap via release of nitric oxide
      from hemoglobin.
AB  - It has recently been shown that nitrosyl complexes of hemoglobin (NO-Hb) are
      sensitive to low-level blue laser irradiation, suggesting that laser irradiation
      can facilitate the release of biologically active nitric oxide (NO), which can
      affect tissue perfusion. The aim of this study was to evaluate the therapeutic
      value of blue laser irradiation for local tissue perfusion after surgical
      intervention. Blood was withdrawn from a rat, exposed to NO and infused back to
      the same rat or used for in vitro experiments. In vitro, an increase of NO-Hb
      levels (electron paramagnetic resonance spectroscopy) up to 15 microM in rat
      blood did not result in the release of detectable amounts of NO (NO selective
      electrode). Blue laser irradiation of NO-Hb in blood caused decomposition of NO
      Hb complexes and release of free NO. Systemic infusion of NO-Hb in rats affected
      neither systemic circulation (mean arterial pressure) nor local tissue perfusion
      (Doppler blood flow imaging system). In contrast, a clear enhancement of local
      tissue perfusion was observed in epigastric flap when elevated NO-Hb levels in
      blood were combined with local He-Cd laser irradiation focused on the left
      epigastric artery. The enhancement of regional tissue perfusion was not
      accompanied by any detectable changes in systemic circulation. This study
      demonstrates that blue laser irradiation improves local tissue perfusion in a
      controlled manner stimulating NO release from NO-Hb complexes.

PMID- 17515955
TI  - Molecular markers in patients with chronic wounds to guide surgical debridement.
AB  - Chronic wounds, such as venous ulcers, are characterized by physiological
      impairments manifested by delays in healing, resulting in severe morbidity.
      Surgical debridement is routinely performed on chronic wounds because it
      stimulates healing. However, procedures are repeated many times on the same
      patient because, in contrast to tumor excision, there are no objective
      biological/molecular markers to guide the extent of debridement. To develop
      bioassays that can potentially guide surgical debridement, we assessed the
      pathogenesis of the patients' wound tissue before and after wound debridement. We
      obtained biopsies from three patients at two locations, the nonhealing edge
      (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers
      (post debridement), and evaluated their histology, biological response to
      wounding (migration) and gene expression profile. We found that biopsies from the
      nonhealing edges exhibit distinct pathogenic morphology
      (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased
      procollagen synthesis). Fibroblasts deriving from this location exhibit impaired
      migration in comparison to the cells from adjacent nonulcerated biopsies, which
      exhibit normalization of morphology and normal migration capacity. The nonhealing
      edges have a specific, identifiable, and reproducible gene expression profile.
      The adjacent nonulcerated biopsies have their own distinctive reproducible gene
      expression profile, signifying that particular wound areas can be identified by
      gene expression profiling. We conclude that chronic ulcers contain distinct
      subpopulations of cells with different capacity to heal and that gene expression
      profiling can be utilized to identify them. In the future, molecular markers will
      be developed to identify the nonimpaired tissue, thereby making surgical
      debridement more accurate and more efficacious.

PMID- 17515956
TI  - Molecular profile of peripheral blood mononuclear cells from patients with
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. Currently,
      diagnosis of RA may take several weeks, and factors used to predict a poor
      prognosis are not always reliable. Gene expression in RA may consist of a unique
      signature. Gene expression analysis has been applied to synovial tissue to define
      molecularly distinct forms of RA; however, expression analysis of tissue taken
      from a synovial joint is invasive and clinically impractical. Recent studies have
      demonstrated that unique gene expression changes can be identified in peripheral
      blood mononuclear cells (PBMCs) from patients with cancer, multiple sclerosis,
      and lupus. To identify RA disease-related genes, we performed a global gene
      expression analysis. RNA from PBMCs of 9 RA patients and 13 normal volunteers was
      analyzed on an oligonucleotide array. Compared with normal PBMCs, 330 transcripts
      were differentially expressed in RA. The differentially regulated genes belong to
      diverse functional classes and include genes involved in calcium binding,
      chaperones, cytokines, transcription, translation, signal transduction,
      extracellular matrix, integral to plasma membrane, integral to intracellular
      membrane, mitochondrial, ribosomal, structural, enzymes, and proteases. A k
      nearest neighbor analysis identified 29 transcripts that were preferentially
      expressed in RA. Ten genes with increased expression in RA PBMCs compared with
      controls mapped to a RA susceptibility locus, 6p21.3. These results suggest that
      analysis of RA PBMCs at the molecular level may provide a set of candidate genes
      that could yield an easily accessible gene signature to aid in early diagnosis
      and treatment.

PMID- 17515957
TI  - An interferon signature in the peripheral blood of dermatomyositis patients is
      associated with disease activity.
AB  - Recent studies have shown increased expression of interferon (IFN)-regulated
      genes in the peripheral blood cells of patients with systemic lupus
      erythematosus. A similar interferon signature has been observed in affected
      muscle tissue from patients with dermatomyositis (DM), but it has not yet been
      determined if this signature extends to the peripheral blood in DM. We performed
      global gene expression profiling of peripheral blood cells from adult and
      juvenile DM patients and healthy controls. Several interesting groups of genes
      were differentially expressed in DM, including genes with immune function, and
      others that function in muscle or are involved in mitochondrial/oxidative
      phosphorylation. Investigation of type I IFN-regulated transcripts revealed a
      striking interferon signature present in most DM patients studied. Levels of type
      I IFN-regulated proteins were also elevated in DM serum samples. Furthermore,
      both the transcript and serum protein IFN signatures were associated with disease
      activity. These data suggest that the IFN signature may be a useful marker for DM
      disease activity, and that sampling peripheral blood may be a more practical
      alternative to muscle biopsy for measuring this signature.

PMID- 17515958
TI  - Interplay of genes regulated by estrogen and diindolylmethane in breast cancer
      cell lines.
AB  - Diindolylmethane (DIM), a biologically active congener of indole-3-carbinol (I3C)
      derived from cruciferous vegetables, is a promising agent for the prevention of
      estrogen-sensitive cancers. Both DIM and estrogen affect transcription of genes
      by binding receptors, such as aryl hydrocarbon receptor (AhR) or estrogen
      receptors (ER). Gene regulation by DIM and estradiol (E2) can be very complex.
      While DIM typically binds the AhR, this complex can directly associate with the
      ER, recruit co-activators that bind to estrogen-responsive promoters, and
      activate transcription. Alternately, DIM can bind the ER directly. In this study,
      we have analyzed gene expression using microarray profiling and quantitative real
      time-polymerase chain reaction in MCF7 breast cancer cells treated with E2 (1 nM)
      or DIM (25 microM) alone or in combination for 16 h. The interplay of E2 and DIM
      was reflected in the expression of a subset of genes (<90) in which the
      combination of E2 and DIM acted either additively or antagonistically to alter
      gene expression.

PMID- 17515959
TI  - Phosphorylation of FAK, PI-3K, and impaired actin organization in CK-positive
      micrometastatic breast cancer cells.
AB  - Several markers have been used to detect circulating tumor cells (CTC) in the
      peripheral blood of patients with breast cancer. However, analysis of activated
      signaling kinases in CTC implicated in cellular transformation, migration, and
      survival has not been addressed so far. In the present study, we focused on the
      phenotypic profile of micrometastatic cells in peripheral blood mononuclear cells
      (PBMC) preparations from 45 breast cancer patients. PBMC cytospins from 28
      cytokeratin (CK)-positive and 17 CK-negative samples were assessed for the
      expression of phosphorylated FAK (p-FAK), phosphorylated PI-3 kinase (p-PI-3K),
      and HER2 using confocal laser scanning microscopy. The expression of p-FAK was
      documented in all 28 CK-positive samples, while all 17 CK-negative samples were
      tested negative for p-FAK. Immunomagnetic separation using EpCAM antibody fully
      confirmed these findings, implying a sound correlation for the co-expression of
      the two molecules. Interestingly, 15 of 28 CK- and p-FAK-positive samples also
      expressed the HER2 oncoprotein. p-PI-3K was documented in 15 of 17 CK- and p-FAK
      positive samples. Immunoblot analysis of micrometastatic cells in co-culture with
      PBMC confirmed the specific expression of both p-FAK and p-PI-3K. Finally,
      impaired actin organization was apparent in CK- and p-FAK/p-PI-3K-positive
      samples, comparable to that observed in MCF-7 human breast cancer cells. Our
      findings provide strong evidence that micrometastatic cells express activated
      signaling kinases, which may regulate migration mechanisms, supporting the
      presumption of their malignant and metastatic nature.

PMID- 17515960
TI  - Subcellular localization of APE1/Ref-1 in human hepatocellular carcinoma:
      possible prognostic significance.
AB  - APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular
      response to oxidative stress. Cytoplasmic localization has been observed in
      several tumors and correlates with a poor prognosis. Because no data are
      available on liver tumors, we investigated APE1/Ref-1 subcellular localization
      and its correlation with survival in 47 consecutive patients undergoing
      hepatocellular carcinoma (HCC) resection. APE1/Ref-1 expression was determined by
      immunohistochemistry in HCC and surrounding liver cirrhosis (SLC) and compared
      with normal liver tissue. Survival probability was evaluated using Kaplan-Meier
      curves (log-rank test) and Cox regression. Cytoplasmic expression of APE1/Ref-1
      was significantly higher in HCC than in SLC (P = 0.00001); normal liver showed
      only nuclear reactivity. Patients with poorly differentiated HCC showed a
      cytoplasmic expression three times higher than those with well-differentiated HCC
      (P = 0.03). Cytoplasmic localization was associated with a median survival time
      shorter than those with negative cytoplasmic reactivity (0.44 compared with 1.64
      years, P = 0.003), and multivariable analysis confirmed that cytoplasmic APE1/Ref
      1 localization is a predictor of survival. Cytoplasmic expression of APE1/Ref-1
      is increased in HCC and is associated with a lower degree of differentiation and
      a shorter survival time, pointing to the use of the cytoplasmic localization of
      APE1/Ref-1 as a prognostic marker for HCC.

PMID- 17515961
TI  - Hepcidin expression in the liver: relatively low level in patients with chronic
      hepatitis C.
AB  - Patients with chronic hepatitis C frequently have serum and hepatic iron
      overload, but the mechanism is unknown. Recently identified hepcidin, exclusively
      synthesized in the liver, is thought to be a key regulator for iron homeostasis
      and is induced by infection and inflammation. This study was conducted to
      determine the hepatic hepcidin expression levels in patients with various liver
      diseases. We investigated hepcidin mRNA levels of liver samples by real-time
      detection-polymerase chain reaction; 56 were hepatitis C virus (HCV) positive, 34
      were hepatitis B virus (HBV) positive, and 42 were negative for HCV and HBV (3
      cases of auto-immune hepatitis, 7 alcoholic liver disease, 13 primary biliary
      cirrhosis, 9 nonalcoholic fatty liver disease, and 10 normal liver). We analyzed
      the relation of hepcidin to clinical, hematological, histological, and
      etiological findings. Hepcidin expression levels were strongly correlated with
      serum ferritin (P < 0.0001) and the degree of iron deposit in liver tissues (P <
      0.0001). Hepcidin was also correlated with hematological parameters (vs.
      hemoglobin, P = 0.0073; vs. serum iron, P = 0.0012; vs. transferrin saturation, P
      < 0.0001) and transaminase levels (P = 0.0013). The hepcidin-to-ferritin ratio
      was significantly lower in HCV(+) patients than in HBV(+) patients (P = 0.0129)
      or control subjects (P = 0.0080). In conclusion, hepcidin expression levels in
      chronic liver diseases were strongly correlated with either the serum ferritin
      concentration or degree of iron deposits in the liver. When adjusted by either
      serum ferritin values or hepatic iron scores, hepcidin indices were significantly
      lower in HCV(+) patients than in HBV(+) patients, suggesting that hepcidin may
      play a pivotal role in the pathogenesis of iron overload in patients with chronic
      hepatitis C.

PMID- 17515962
TI  - SERCA2a, phospholamban, sarcolipin, and ryanodine receptors gene expression in
      children with congenital heart defects.
AB  - In animal models of conotruncal heart defects, an abnormal calcium sensitivity of
      the contractile apparatus and a depressed L-type calcium current have been
      described. Sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) is a membrane
      protein that catalyzes the ATP-dependent transport of Ca(2+) from the cytosol to
      the SR. The activity of SERCA is inhibited by phospholamban (PLN) and sarcolipin
      (SLN), and all these proteins participate in maintaining the normal intracellular
      calcium handling. Ryanodine receptors (RyRs) are the major SR calcium-release
      channels required for excitation-contraction coupling in skeletal and cardiac
      muscle. Our objective was to evaluate SERCA2a (i.e., the SERCA cardiac isoform),
      PLN, SLN, and RyR2 (i.e., the RyR isoform enriched in the heart) gene expression
      in myocardial tissue of patients affected by tetralogy of Fallot (TOF), a
      conotruncal heart defect. The gene expression of target genes was assessed
      semiquantitatively by RT-PCR using the calsequestrin (CASQ, a housekeeping gene)
      RNA as internal standard in the atrial myocardium of 23 pediatric patients
      undergoing surgical correction of TOF, in 10 age-matched patients with
      ventricular septal defect (VSD) and in 13 age-matched children with atrial septal
      defect (ASD). We observed a significantly lower expression of PLN and SLN in TOF
      patients, while there was no difference between the expression of SERCA2a and
      RyR2 in TOF and VSD. These data suggest a complex mechanism aimed to enhance the
      intracellular Ca(2+) reserve in children affected by tetralogy of Fallot.

PMID- 17515964
TI  - Cataract services: increasing utilisation and creating demand.

PMID- 17515963
TI  - Factor XIIIA-V34L and factor XIIIB-H95R gene variants: effects on survival in
      myocardial infarction patients.
AB  - It has been demonstrated recently that coagulation factor XIII (FXIII) plays an
      extraordinary role in myocardial healing after infarction, improving survival in
      a mouse model. Common FXIII gene variants (i.e. FXIIIA-V34L and FXIIIB-H95R)
      significantly influence the molecular activity. To evaluate whether there is a
      relationship between the two FXIII gene variants and survival in patients after
      myocardial infarction (MI), V34L and H95R were PCR-genotyped in a cohort of 560
      MI cases and follow-up was monitored. Cases with ST-segment elevation MI (STEMI)
      were 416 (74.3%) and 374 of these were treated with primary percutaneous coronary
      intervention (PCI) (89.9%). The remaining 144 patients showed non-ST-segment
      elevation MI (NSTEMI) at enrollment. The combined endpoint was the occurrence of
      death, re-infarction, and heart failure. Kaplan-Meier analysis at one year
      yielded an overall rate for adverse events of 24.5% with a lower incidence in the
      L34-carriers (28.8% vs 17.1%; log-rank, P = 0.00025), similar to that of the 416
      STEMI (23.8%) being (28.0% and 16.9%; VV34- and L34-carriers respectively; log
      rank, P = 0.001). Primary PCI-group had a slight lower incidence (22.9%) of
      adverse events (26.8% and 17.1%; VV34- and L34-carriers respectively; log-rank, P
      = 0.009). During hospitalization, 506 patients received PCI (374 primary PCI and
      132 elective PCI). Significance was conserved also in the overall PCI-group
      (28.6% and 17.8%; VV34- and L34-carriers respectively; log-rank, P = 0.001).
      Similar findings were observed at 30 days follow-up. Cases carrying both FXIII
      variants had improved survival rate (log-rank, P = 0.019). On the other hand,
      minor bleeding complications were found increased in L34-carriers (P = 0.0001)
      whereas major bleeding complications were not. Finally, more direct evidence on
      the role of FXIII molecule on survival might come from the fact that despite
      significant FXIII antigen reductions observed in cases after MI, regardless the
      FXIII genotype considered, L34-carriers kept almost normal FXIII activity (VV34-
      vs L34-carriers; P < 0.001). We conclude that FXIII L34-allele improves survival
      after MI in all the groups analyzed, possibly through its higher activity
      associated with assumable positive effects on myocardial healing and recovered
      functions. Genetically determined higher FXIII activity might influence post-MI
      outcome. This paves the way for using FXIII molecules to improve myocardial
      healing, recovery of functions, and survival after infarction.

PMID- 17515965
TI  - Increasing uptake of eye services by women.

PMID- 17515966
TI  - Increasing the volume of cataract surgery: an experience in rural China.

PMID- 17515967
TI  - Popularising eye health services in southern Mexico: community workers meet a
      felt need.

PMID- 17515968
TI  - Creating demand for cataract services: a Cambodian case study.

PMID- 17515969
TI  - Increasing the use of cataract services: using an existing eye care structure in
      Nigeria.

PMID- 17515970
TI  - Rapid assessment of avoidable blindness.

PMID- 17515972
TI  - Courses and conferences.

PMID- 17515971
TI  - How to avoid mistakes in biometry.

PMID- 17515974
TI  - Research and training programmes.

PMID- 17515973
TI  - Useful resources: increasing uptake and generating demand for cataract services.

PMID- 17515975
TI  - Practical research: a basic outline for mid-level eye personnel.

PMID- 17515976
TI  - Community Eye Health MSc dissertations.

PMID- 17515977
TI  - Care of instruments and equipment: a success story.

PMID- 17515978
TI  - Awareness about eye diseases among diabetic patients: a survey in South India.

PMID- 17515979
TI  - Glossary: research and training.

PMID- 17515980
TI  - Useful resources: research and training programmes.

PMID- 17515982
TI  - [IV Brazilian Guideline for Dyslipidemia and Atherosclerosis prevention:
      Department of Atherosclerosis of Brazilian Society of Cardiology].

PMID- 17515983
TI  - Relationship between the iron status of pregnant women and their newborns.
AB  - OBJECTIVE: To determine the relationship between iron nutritional status of
      pregnant women and their newborns using a combination of hematological and
      biochemical parameters for the diagnosis of iron deficiency. METHODS: A cross
      sectional study was conducted in Jundiai, Southeastern Brazil, in 2000. Venous
      blood samples collected from 95 pregnant women and from their umbilical cord and
      used for the determination of complete blood count, serum iron, total iron
      binding capacity, serum ferritin, zinc protoporphyrin, and transferrin
      saturation. Women were classified into three groups: anemic, iron deficient and
      non-iron deficient. Statistical analysis included the Tukey-HSD test, Pearson's
      correlation coefficient and multiple linear regression analysis. RESULTS: Among
      pregnant women, 19% were anemic (97.9% mildly anemic and 2.1% moderately anemic)
      and 30.5% were iron deficient. No significant difference was seen in mean values
      of any parameter studied between newborns in the three groups (p>0.05). Multiple
      linear regression analysis showed weak association between neonatal and maternal
      parameters. CONCLUSIONS: The iron nutritional status of pregnant women with iron
      deficiency or mild anemia does not seem to have a significant impact on the iron
      levels of their children.

PMID- 17515984
TI  - [Anemia in children under six: population-based study in Pelotas, Southern
      Brazil].
AB  - OBJECTIVE: To assess the prevalence of anemia among children under six years of
      age in a probabilistic sample from an urban area. METHODS: A study was conducted
      comprising children aged zero to five years in the city of Pelotas, Southern
      Brazil, in 2004. Data were collected on demographic, socioeconomic, and
      anthropometric characteristics, morbidity and nutrition using a questionnaire
      applied to the mothers and guardians. Children's weight and height measurements
      were obtained. Hemoglobin concentration was measured using the HemoCue portable
      hemoglobinometer and anemia was defined as hemoglobin <11 g/dL. The association
      between anemia and predictors was expressed as prevalence ratio. Multivariate
      analysis was carried out using Poisson regression following a conceptual model
      and taking into account the study design effect. RESULTS: There were identified
      534 children and total losses and refusals were 27 (5.1%). The prevalence of
      anemia was 30.2% (95% CI 23.5%; 37.0%). In the multivariate analysis, only age
      and family income remained significantly associated with anemia. CONCLUSIONS:
      Anemia was largely socially determined in the population studied. Interventions
      aiming at reducing anemia should be developed to lessen this condition in the
      short run targeting disadvantaged populations.

PMID- 17515985
TI  - [Frequency of high-fat and low-fiber diets among adolescents].
AB  - OBJECTIVE: To describe the frequency and associated factors of high-fat and low
      fiber diets among adolescents. METHODS: A cross-sectional study was carried out
      in adolescents aged 10-12 years in Pelotas, southern Brazil, in 2004 and 2005.
      Dietary patterns in the previous 12 months were evaluated using the Block
      questionnaire comprising 24 food items scored according to the frequency of
      consumption of high-fat and low-fiber food. In the crude analysis, the prevalence
      of high-fat and low-fiber diets were compared according to subgroups of
      independent variables (sex, skin color, socioeconomic condition, maternal
      schooling and adolescent's nutritional status). In order to adjust for
      confounders, multivariable analysis using Poisson's regression was carried out
      for each outcome. RESULTS: There were 4,452 adolescents included in the study,
      most of them (83.9%) had low-fiber diets and more than one third (36.6%) had high
      fat diets. Socioeconomic condition and maternal schooling were directly
      associated with consumption of high-fat diets. Adolescents from socioeconomic
      groups A+B and C had lower prevalence of low-fiber diet. CONCLUSIONS: The
      prevalence of low-fiber and high-fat diets was high in this population of
      adolescents. Public policies targeting the determinants of dietary habits are
      necessary and urgent.

PMID- 17515986
TI  - Effects of breastfeeding and sucking habits on malocclusion in a birth cohort
      study.
AB  - OBJECTIVE: To estimate the prevalence of malocclusion and to examine the effects
      of breastfeeding and non-nutritive sucking habits on dentition in six-year-old
      children. METHODS: A cross-sectional study was carried out nested into a birth
      cohort conducted in Pelotas, Southern Brazil, in 1999. A sample of 359 children
      was dentally examined and their mothers interviewed. Anterior open bite and
      posterior cross bite were recorded using the Foster & Hamilton criteria.
      Information regarding breastfeeding and non-nutritive sucking habits was
      collected at birth, in the first, third, sixth and 12th months of life, and at
      six years of age. Control variables included maternal schooling and child's
      birthweight, cephalic perimeter, and sex. Data were analyzed by Poisson
      regression. RESULTS: Prevalence of anterior open bite was 46.2%, and that of
      posterior cross bite was 18.2%. Non-nutritive sucking habits between 12 months
      and four years of age and digital sucking at age six years were the main risk
      factors for anterior open bite. Breastfeeding for less than nine months and
      regular use of pacifier between age 12 months and four years were risk factors
      for posterior cross bite. Interaction between duration of breastfeeding and the
      use of pacifier was identified for posterior cross bite. CONCLUSIONS: Given that
      breastfeeding is a protective factor for other diseases of infancy, our findings
      indicate that the common risks approach is the most appropriate for the
      prevention of posterior cross bite in primary or initial mixed dentition.

PMID- 17515987
TI  - [Risk factors for acute respiratory disease hospitalization in children under one
      year of age].
AB  - OBJECTIVE: To evaluate risk factors for acute respiratory disease
      hospitalizations in children under one year of age. METHODS: A case-control study
      was conducted in the city of Pelotas, Southern Brazil. Cases were children under
      one year of age who were hospitalized due to acute respiratory diseases from
      August 1997 to July 1998. Controls were same-age community children randomly
      selected without previous respiratory disease hospitalization. A questionnaire
      about risk factors exposure was applied to the mothers of cases and controls.
      Univariate, bivariate and multivariate analyses through logistic regression were
      carried out to evaluate risk factors for the outcome of interest. RESULTS: There
      were studied 777 children; 625 cases and 152 controls. In the crude analysis, the
      risk factors associated with the outcome were: being male, children under six
      months of age, household crowding, maternal education, family income, inadequate
      housing conditions, lack of breastfeeding, maternal smoking, use of pacifiers,
      and a previous history of hospitalization and respiratory symptoms. Maternal
      working was a protection factor associated with acute respiratory disease
      hospitalizations. In the multivariate analysis the following risk factors
      remained associated: maternal education (OR=12.5), previous history of wheezing
      (OR=7.7), lack of breastfeeding (OR=2.3), use of pacifiers (OR=1.9), maternal
      smoking (OR=1.7), children under six months of age (OR=1.7), and being male
      (OR=1.5). CONCLUSIONS: The study results show the importance of the family's
      social and behavioural aspects as well as previous respiratory disease as risk
      factors for acute respiratory disease hospitalizations in children under one year
      of age.

PMID- 17515988
TI  - [Violence against women attending public health services in the metropolitan area
      of Sao Paulo, Brazil].
AB  - OBJECTIVE: To estimate the prevalence of (physical, psychological, and sexual)
      violence against women by an intimate partner and non-partner perpetrators among
      users of public health services and to compare these women's perception of having
      ever experienced violence with reports of violence in their medical records in
      the different services studied. METHODS: The study was conducted in 19 health
      services, selected as a convenience sample and grouped into nine research sites,
      in metropolitan area of Sao Paulo from 2001 to 2002. Questionnaires on having
      ever experienced violence in their lifetime and in the last 12 months and
      perpetrators were applied to a sample of 3,193 users aged 15 to 49. A total of
      3,051 medical records were reviewed to verify the notification of violence.
      Comparative analyses were performed by Anova with multiple comparisons and Chi
      square test followed by its partition. RESULTS: The following prevalences were
      found: any type of violence 76% (95% CI: 74.2; 77.8); psychological 68.9% (95%
      CI: 66.4; 71.4); physical 49.6% (95% CI: 47.7; 51.4); physical and/or sexual
      54.8% (95% CI: 53.1; 56.6), and sexual 26% (95% CI: 24.4; 28.0). The prevalence
      of physical and/or sexual violence by an intimate partner in their lifetime was
      45.3% (95% CI: 43.5; 47.1), and by non-partners was 25.7% (95% CI: 25.0; 26.5).
      Only 39.1% of women reporting any episode of violence perceived they had ever
      experienced violence in their lifetime and 3.8% of them had any reports of
      violence in their medical records. The prevalences were significantly different
      between sites as well as the proportion of perception and reports of violence in
      medical records. CONCLUSIONS: The expected high magnitude of the event and its
      invisibility was confirmed by low rate of reports in the medical records. Few
      perceived abuses as violence. Further studies are recommended taking into account
      the diversity of service users.

PMID- 17515989
TI  - [Control of arterial hypertension in a family care unit].
AB  - OBJECTIVE: To assess the impact of the implementation of the Family Health Care
      Program for arterial hypertension management in a primary care unit. METHODS:
      There were studied 135 patients with confirmed diagnosis of arterial hypertension
      (45 patients from each primary care team) who received treatment between December
      2003 and December 2004 and were followed up until July 2005 in the city Salvador,
      Northeastern Brazil. Blood pressure measures were compared at baseline and at the
      end of the follow-up period, and their association with cardiovascular risk
      factors and variables such as gender, age, body mass index, number of medical
      visits, number of antihypertensive drugs taken by patients, education level and
      family income were evaluated. Data were described as means and standard
      deviations, absolute and percentual values and the Wilcoxon, Kruskal-Walis and
      Chi-square tests were performed. RESULTS: Mean blood pressures at baseline and at
      the end of the follow-up were 155.9+/-24.1/95.3+/-13.9 mmHg and 137.2+/
      16.1/86.7+/-8.7 mmHg (p<0.01), respectively. At starting treatment, 28.9%
      hypertense patients had well-controlled blood pressure levels (<140/90 mmHg)
      compared to 57% at the end of the follow-up period (p<0.01). The mean number of
      medical visits was 10.1+/-3.9, with 91.8% compliance. Two antihypertensive drugs
      were used by 50.4% and one drug by 35.6% of the patients. The prevalences of
      associated risk factors assessed at entering the program were overweight/obesity
      (71.9%), dyslipidemia (58.5%) and diabetes/impaired fasting glucose (43.7%). The
      results of the different care teams were comparable. CONCLUSIONS: The
      implementation of the Family Health Care Program has provided a better management
      of arterial hypertension but the associated risk factors have remained at higher
      levels than those recommended and thus needing better management.

PMID- 17515990
TI  - [Capture of culicids in urban areas: evaluation of the resting box method].
AB  - OBJECTIVE: To evaluate the occurrence of adult culicid populations in urban areas
      and measure the sensitivity of the resting box collection method. METHODS:
      Mosquito were collected in 1999 and 2000, in two cities in the State of Sao
      Paulo, Brazil: Ocaucu and Uchoa. In each city, 15 blocks were drawn by lots and
      then one home in each block was drawn. Two resting boxes were installed at each
      home: one inside and the other outside the house. Monthly collections were
      carried out at each home, over a 13-month period, using manual aspirators inside
      and outside the home and inside the boxes. The captured specimens were taken to
      the laboratory for screening and identification according to species and sex.
      RESULTS: Out of the 2,112 culicid specimens collected, 99.7% were of four
      species: Culex quinquefasciatus, Aedes aegypti, Cx. declarator and Cx. coronator.
      The distribution of these species in Ocaucu was 83.3%, 3.2%, 10.8% and 24%,
      respectively, and in Uchoa it was 83.8%, 8.4%, 4.4% and 3.0%, respectively. Among
      the females of the genus Culex, 34.3% were captured in the resting boxes and
      59.9% were collected from inside the house. Among the females of Ae. aegypti,
      17.6% were found in the resting boxes and 82.4% inside the home. CONCLUSIONS: The
      great majority of the specimens collected belonged to four species of culicids,
      and Cx. quinquefasciatus was the most common. Proportionally, the females of Ae.
      aegypti were found more inside the home than were those of the genus Culex.
      Resting boxes present potential for use as surveillance devices, but their use
      needs to be more thoroughly evaluated.

PMID- 17515991
TI  - [Light and hens as attraction factors of Nyssomyia whitmani in a rural area,
      Southern Brazil].
AB  - OBJECTIVE: To verify the influence of traps with electric light and hens as
      factors that attract sandflies and compare results between capture methods.
      METHODS: The study was conducted in the Palmital Farm, Southern Brazil. Sandfly
      collections were conducted with Falcao traps and an electric aspirator,
      fortnightly, between 8 p.m. and 11 p.m. in the presence or absence of light and
      hens in peridomiciliary areas, from September 1998 to June 1999. RESULTS: A total
      of 43,767 specimens from eight species of sandflies were collected: Nyssomyia
      whitmani, N. neivai and Migonemyia migonei constituting 99.9% of the total
      collected, with predominance of N. whitmani. The number of this species collected
      inside the hen's shed in the presence of hens (21,045) was greater than in their
      absence (10,434). In the presence of hens, with distinct intensities of light, a
      larger number of N. whitmani samples were collected with 3W light. In the
      presence of hens and light (3W), the number of N. whitmani collected with the
      electric aspirator (5,141) was superior to that collected with the Falcao trap
      (1,675). In the absence of light, with or without the presence hens, there was no
      difference between the numbers of N. whitmani collected with the electric
      aspirator or the Falcao trap. CONCLUSIONS: Hens and electric light together
      attract more N. whitmani to peridomicilary areas. The number of N. whitmani
      collected with an electric aspirator inside a hen's shed with the presence of
      hens and light is greater than those collected with a Falcao trap in the same
      conditions.

PMID- 17515992
TI  - [Rabies virus in naturally infected bats in the State of Sao Paulo, Southeastern
      Brazil].
AB  - OBJECTIVE: To identify the species of bats involved in maintaining the rabies
      cycle; to investigate the distribution of the rabies virus in the tissues and
      organs of bats and the time taken for mortality among inoculated mice. METHODS:
      From April 2002 to November 2003, bats from municipalities in the State of Sao
      Paulo were screened for the presence of the rabies virus, by means of direct
      immunofluorescence. The virus distribution in the bats was evaluated by
      inoculating mice and N2A cells with 20% suspensions prepared from fragments of
      different organs and tissues, plus the brain and salivary glands. The time taken
      for mortality among the mice was monitored daily, following intracerebral
      inoculation. RESULTS: Out of the 4,395 bats received, 1.9% were found positive
      for the rabies virus. They belonged to ten genera, with predominance of
      insectivores. The maximum mean times taken for mortality among the mice following
      inoculation with brain and salivary gland material were 15.33+/-2.08 days and
      11.33+/-2.30 days for vampire bats, 16.45+/-4.48 days and 18.91+/-6.12 days for
      insectivorous bats, and 12.60+/-2.13 days and 15.67+/-4.82 days for frugivorous
      bats, respectively. CONCLUSIONS: The species infected with the rabies virus were:
      Artibeus lituratus, Artibeus sp., Myotis nigricans, Myotis sp., Eptesicus sp.,
      Lasiurus ega, Lasiurus cinereus, Nyctinomops laticaudatus, Tadarida brasiliensis,
      Histiotus velatus, Molossus rufus, Eumops sp. and Desmodus rotundus. Virus
      investigation in the different tissues and organs showed that the brain and
      salivary glands were the most suitable sites for virus isolation.

PMID- 17515993
TI  - [Alcohol and adolescents: study to implement municipal policies].
AB  - OBJECTIVE: To build students' profile regarding alcohol consumption and risk
      behavior. METHODS: A total of 1,990 students were included in the study, aged 11
      to 21 years old, from both genders, enrolled in public and private schools, in
      Southeastern Brazil, in 2004. A self-administered questionnaire was answered in
      the classroom without the presence of the teacher. The questionnaire also
      assessed the perception of how easy it was to get alcoholic beverages, the
      contexts where they drunk, and the consequences of drinking. RESULTS: Prevalence
      of lifetime alcohol use was 62.2%. Regarding consumption in the last 30 days,
      17.3% of students reported at least one episode of binge drinking (five or more
      drinks). Adolescents reported that they had gotten alcoholic drinks very easily
      from shops, and also in social contexts with relatives and friends. Only 1% of
      underaged reported that they had tried and could not buy alcoholic beverages. As
      negative consequences of alcohol use in the last 12 months, students reported
      feeling sick due to drinking (17.9%), regret for doing something under the
      influence of alcohol (11%), blackouts (9.8%), and getting involved in a fight
      after drinking (5%). Over half of the students (55%) reported knowing someone who
      had been involved in a car accident because of a drunk driver. CONCLUSIONS: Data
      showed high prevalence of alcohol use among adolescents studied and how easy
      access to alcoholic beverages is, including to underaged people. Youngsters put
      themselves at risk and presented negative consequences of alcohol consumption.
      Prompt actions regarding public alcohol policies in Brazil are needed.

PMID- 17515994
TI  - [Knowledge and practices by adolescents in preventing occupational injuries: a
      qualitative study].
AB  - OBJECTIVE: To describe knowledge and practices adopted by high school students to
      prevent occupational injuries. STUDY DESIGN: The study was carried out in a
      public school located in Sao Paulo, in 2003. Fifty-three evening students aged 14
      to 21 years old participated the study, they were divided into two groups with
      and without job experience (32 and 21 students, respectively). The students
      answered two questions: "Why do occupational injuries occur?" and "How do you
      avoid occupational injuries?" Analyses were performed using the software "Quali
      quanti" to structure collective discourses. ANALYSIS OF DISCOURSES: Adolescents
      with work experience reported that occupational injuries occur due to
      carelessness of the employee, bad luck of the employee, employer's negligence,
      lack of training, and unsafe workplace. Adolescents without work experience
      reported that the main causes of work injuries were carelessness of the employee
      and employer's negligence. Regarding the ways to protect themselves against
      occupational injuries, both groups reported that: they pay attention (would pay
      attention) and wear safety equipment (would wear) safety equipment. CONCLUSIONS:
      Adolescents from both groups showed limited knowledge about occupational injuries
      and prevention methods. Students "blamed the victim" to explain the injuries and
      considered "paying attention to work" as the best way to protect themselves.
      These facts showed that the culture of blaming the victim is present since
      adolescence and probably it is an outcome of a learning process of the society.

PMID- 17515995
TI  - [AIDS in rural Minas Gerais state (Southeastern Brazil): a cultural approach].
AB  - OBJECTIVE: To describe behaviors facilitating HIV/AIDS exposure in rural
      population. METHODS: A qualitative study was conducted comprising 52 patients who
      attended a STD/AIDS outpatient clinic in 2002 and 2003. In-depth open and semi
      structured interviews were carried out with subjects (30 males, 22 females) at
      the clinic or at home in rural municipalities in the northern area of Minas
      Gerais state, Southeastern Brazil. Interviews were transcribed and analyzed
      considering categories such as disease, work, social life, prior HIV/AIDS
      knowledge, and lifestyle. Content analysis was used for result interpretation.
      RESULTS: Interviewees perceived AIDS as a "big city disease", an "outsider's
      disease", dissociated from local culture. They were all infected through either
      heterosexual or homosexual sex. Rural-urban migration is a major factor for HIV
      infection in the area as people migrate to search for jobs. CONCLUSIONS: Popular
      beliefs about HIV/AIDS disease contributes to HIV vulnerability of this
      population. There is a need to apprehend their cultural beliefs to better
      understand their ways of thinking and to focus on these local beliefs when
      disseminating HIV/AIDS information.

PMID- 17515996
TI  - [Portuguese version of the Family Environment Scale: application and validation].
AB  - OBJECTIVE: To translate the Family Environment Scale into Portuguese and apply
      the instrument to validate it. METHODS: The translation was applied to members of
      Brazilian families with the aim of evaluating its internal consistency and the
      concordance between members of the same family. One hundred and fifty-four
      volunteers living in the city of Sao Paulo in 2003 who were not receiving any
      kind of intervention for dealing with family problems were selected. The mean
      scores in the ten subscales of the instrument were compared between men and
      women, and between members of the same family. The internal consistency was
      evaluated by means of Cronbach's alpha. RESULTS: The maximum possible score in
      each subscale was nine (good family functioning), except in relation to conflict
      and control. In most of the subscales, the mean score of the sample studied
      ranged from 5.1 to 7.6 (men) and 5.4 to 7.7 (women). In the conflict and control
      subscales, the means ranged from 1.8 to 4.6 (men) and 1.6 to 4.6 (women). These
      were similar to scores reported in international studies, except for higher
      scores in the cohesion and organization subscales, and lower score in the
      conflict subscale. There were no statistically significant differences between
      the scores attained by men and women. The reliability of the scale, evaluated
      according to Cronbach's alpha, ranged from 0.61 to 0.78 for the ten subscales.
      CONCLUSIONS: Cultural factors may have influenced the results obtained in some of
      the subscales. The Portuguese version of the Family Environment Scale presented
      reasonable internal consistency that enables its use for evaluating changes in
      the family's environment and its functioning and after therapeutic interventions.

PMID- 17515997
TI  - [Data envelopment analysis for evaluating public hospitals in Brazilian state
      capitals].
AB  - OBJECTIVE: To apply the Data Envelopment Analysis (DEA) methodology for
      evaluating the performance of public hospitals, in terms of clinical medical
      admissions. METHODS: The efficiency of the hospitals was measured according to
      the performance of decision-making units in relation to the variables studied for
      each hospital, in the year 2000. Data relating to clinical medical admissions in
      hospitals within the public system in Brazilian state capitals and Federal
      District (mortality rate, mean length of stay, mean cost of stay and disease
      profile) were analyzed. The canonical correlation analysis technique was
      introduced to restrict the variation range of the variables used. The constant
      returns to scale model was used to generate scores that would enable assessment
      of the efficiency of the units. From the scores obtained, these cities were
      classified according to their relative performance in the variables analyzed. It
      was sought to correlate between the classification scores and the exogenous
      variables of the expenditure on primary care programs per inhabitant and the
      human development index for each state capital. RESULTS: In the hospitals
      studied, circulatory diseases were the most prevalent (23.6% of admissions), and
      the mortality rate was 10.3% of admissions. Among the 27 state capitals, four
      reached 100% efficiency (Palmas, Macapa, Teresina and Goiania), seven were
      between 85 and 100%, ten were between 70 and 85% and ten had efficiency of less
      than 70%. CONCLUSIONS: The tool utilized was shown to be applicable for
      evaluating the performance of public hospitals. It revealed large variations
      among the Brazilian state capitals in relation to clinical medical admissions.

PMID- 17515998
TI  - [Quality of death statistics by unknown causes in Brazilian states].
AB  - OBJECTIVE: To evaluate the quality of reported adult deaths by unknown causes and
      to explore their relationships with some indicators. METHOD: There were evaluated
      adult deaths by unknown causes for all Brazilian federal units from 1990 to 2000.
      Criteria were established to categorize the overall proportion of deaths by
      quality into four groups. The age patterns of ill-defined causes were represented
      by typical states and correlation coefficients between these causes and other
      indicators were estimated, such as external causes and urbanization level.
      RESULTS: "Good" quality data was found in the South-Southeast regions and "fair"
      quality in the North-Northeast regions. Improvement on reported deaths was seen
      in half of the states, especially for women. The proportion of ill-defined deaths
      increased with age and a strong association with death coverage, urbanization
      level and external causes was verified. CONCLUSIONS: Although lowered quality of
      reported deaths by basic causes was seen in several Brazilian states, the overall
      quality can be considered at least as satisfactory. This means the explanatory
      power of death statistics by defined causes can be recovered.

PMID- 17515999
TI  - Sensitivity analysis for unmeasured confounders using an electronic spreadsheet.
AB  - In studies assessing the effects of a given exposure variable and a specific
      outcome of interest, confusion may arise from the mistaken impression that the
      exposure variable is producing the outcome of interest, when in fact the observed
      effect is due to an existing confounder. However, quantitative techniques are
      rarely used to determine the potential influence of unmeasured confounders.
      Sensitivity analysis is a statistical technique that allows to quantitatively
      measuring the impact of an unmeasured confounding variable on the association of
      interest that is being assessed. The purpose of this study was to make it
      feasible to apply two sensitivity analysis methods available in the literature,
      developed by Rosenbaum and Greenland, using an electronic spreadsheet. Thus, it
      can be easier for researchers to include this quantitative tool in the set of
      procedures that have been commonly used in the stage of result validation.

PMID- 17516000
TI  - [Evolution of the epidemiological research on physical activity in Brazil: a
      systematic review].
AB  - OBJECTIVE: To describe the evolution of the epidemiological research on physical
      activity in Brazil. METHODS: A systematic review of the literature was carried
      out in electronic databases (Medline/PubMed, Lilacs, Ovid, Science Direct, BioMed
      Central and High Wire), non-indexed Brazilian journals, query by specific
      authors, and contact with other researchers. The inclusion criteria were: the
      sample should be representative of a defined population; sample size equal to or
      greater than 500 individuals; data collection in Brazil; measurement of physical
      activity; and report of data on this variable. RESULTS: A total of 42 studies
      were reviewed. The first study was published in 1990, and there has been a clear
      growth in the number of publications since 2000. Great regional disparities were
      seen and most studies were carried out in the Southeast and South regions. Almost
      all studies (93%) used questionnaires but operational definitions of sedentary
      lifestyle and questionnaires used varied markedly across studies preventing
      result comparisons. CONCLUSIONS: Although the literature on physical activity in
      Brazil has quantitatively increased, methodological limitations make it difficult
      to compare study results. Therefore, standardization of instruments and
      definitions is essential for the improvement of scientific knowledge in the area.

PMID- 17516001
TI  - [Persecutory health].
AB  - A critical approach from the standpoint of social philosophy is taken aiming at
      analyzing aspects of current production of knowledge and technologies in health
      promotion. Its capacity of generating perplexities, dilemmas and dissatisfactions
      is also evaluated, despite its strength and effectiveness in many levels. The
      analysis is based on Ivan Illich's "social iatrogenesis," Peter Skrabanek's
      "coercive healthism," and Giorgio Agamben's theoretical approach of "homo sacer"-
      a man whose life is worthless. The limits and dilemmas of the idea of personal
      responsibility are discussed as a persuasion strategy in health promotion
      discourses and practices. All these proposals produce "persecutory health" as a
      side effect.

PMID- 17516002
TI  - [Straus: the two medical sociologies].
AB  - Robert Straus' pioneer work, "The nature and status of Medical Sociology,"
      written in 1957, was reviewed. Straus, one of the founders of medical sociology,
      made major contributions to this field and created the first department of
      behavior sciences in a medical school. In the work reviewed, Straus establishes
      the differences between sociology in medicine and medical sociology. Comments are
      made on the current perspective of medical sociology and about the author.

PMID- 17516003
TI  - [Responsibility of health providers in domestic violence reporting].
AB  - Domestic violence reporting by health providers contributes to the
      epidemiological assessment of the magnitude of the problem, which allows the
      development of specific programs and actions. The aim of the study was to assess
      the level of responsibility of these providers towards reporting violence,
      especially domestic violence, and potential related legal and ethical
      implications. The Brazilian legislation and ethics code of Medicine, Dentistry,
      Nursing and Psychology were studied. Legal sanctions are found in the Criminal
      Law of Misdemeanor Offenses, the Child and Adolescent Statute, the Elderly
      Statute and in the law establishing mandatory reporting of violence against
      women. There are also penalties in all ethics codes reviewed. It is concluded
      that health providers have the legal duty of reporting known domestic violence
      cases and they can even be charged with omission.

PMID- 17516004
TI  - [Aedes albopictus seasonality in a protected area in the city of Sao Paulo,
      Brazil].
AB  - The study had the objective of assessing the seasonality of Aedes albopictus and
      the impact of environmental factors on breeding sites in a protected urban area.
      Immature individuals were collected through fluid aspiration from nine tree
      holes, in the Ecological Park of Tiete in the city of Sao Paulo, Southern Brazil,
      from 2001 to 2002. The index of positivity and number of individuals results were
      as follows: positivity x precipitation (rho=0.69, p<0.001), positivity x
      temperature (rho=0.35, p<0.001), number of individuals x precipitation (rho=0.29,
      p<0.001) and number of individuals x temperature (rho=0.13, p<0.05). These
      correlations suggest rainfalls had greater impact than temperature.

PMID- 17516005
TI  - Pediculosis: a health problem in the camps of the Iranian former prisoners of war
      in Iraq.

PMID- 17516006
TI  - [Brazilian Ministry of Health performance on Science & Technology].

PMID- 17516007
TI  - [Epidemiological surveillance at hospital level].

PMID- 17516009
TI  - The quality of COPD care in general practice in Denmark: the KVASIMODO study.
AB  - AIM: We studied the quality of care for COPD patients in a large sample of
      general practices in Denmark. We focussed on whether participation by general
      practitioners (GPs) in an educational programme could enhance the use of
      spirometry in the diagnosis and staging of the disease and improve adherence to
      COPD guidelines. METHODS: We performed two audit surveys of GPs' patients' notes,
      one year apart, before and after an educational programme for participating GPs
      and their staff. A total of 154 GPs participated in the study. 2549 patient
      records were included in the first survey and 2394 in the second. RESULTS: Based
      on analysis of all patient records, we observed a substantial improvement in the
      quality of care: recording of FEV1 improved from 52.7% of cases in the first
      survey to 71.4% in the second (p< 0.001). There was a significant improvement in
      the recording of body mass index and provision of smoking cessation advice,
      recommendation of physical activity, checking of inhalation technique, dietary
      instruction, and referral to pulmonary rehabilitation. We also found a decline in
      the use of inhaled corticosteroids in patients with mild COPD, from 60.2% in the
      first survey to 48.8% in the second. When analysing the results focussing on the
      performance of single GPs there was an improvement in quality, but this was less
      than the improvement for patients overall - suggesting that improvement in
      quality of care was not equally distributed throughout the GPs' practices.
      CONCLUSION: We conclude that it is possible to improve the quality of COPD care
      by educating GPs and their staff.

PMID- 17516010
TI  - Do people self-reporting information about chronic respiratory disease have
      corroborative evidence in their general practice medical records? A study of
      intermethod reliability.
AB  - AIMS: To use intermethod reliability to compare self-reported data about chronic
      respiratory disease and health service utilisation with data contained in general
      practice medical records. METHODS: Self-reported postal questionnaire information
      from a small cohort of an age-sex stratified sample of 2318 patients was compared
      with information contained in their medical records. The agreement between the
      two sources of information was assessed. RESULTS: The case notes of 115/135
      individuals from eight general practices were examined. For self-reported chest
      injury or operation (kappa, kappa=-0.03), or chronic bronchitis (kappa=0.10),
      agreement was poor. Agreement for self-reported pleurisy (kappa=0.32), hay fever
      or rhinitis (kappa=0.40), or eczema or dermatitis (kappa=0.30) was fair; for
      chronic obstructive pulmonary disease (COPD) or emphysema (kappa=0.56), or heart
      trouble (kappa=0.54), agreement was moderate; for asthma (kappa=0.78) or
      pneumonia (kappa=0.62), agreement was good; and for pulmonary tuberculosis
      (kappa=0.88), agreement was very good. The strength of agreement for information
      about health service utilisation for respiratory problems ranged from moderate to
      very good and was good for smoking status. CONCLUSIONS: Although based on small
      numbers, our results suggest good or very good agreement between self-reported
      data and general practice medical records for the absence or presence of some
      respiratory conditions and some types of respiratory-related health care
      utilisation. Depending on the research question being examined self-reported
      information may be appropriate.

PMID- 17516011
TI  - Can general practitioner-held data substitute for self-reporting of respiratory
      morbidity and health care utilisation?

PMID- 17516012
TI  - Psychological consequences of a firework factory disaster in a local community.
AB  - OBJECTIVE: This study assessed the prevalence of post-traumatic stress disorder
      (PTSD) and other psychological consequences of an explosion disaster in a
      residential area in Kolding, Denmark, in November 2004. METHOD: A community
      sample of 516 evacuated adults and a control group of 119 residents situated near
      the disaster area, but not affected by the explosion were assessed 3 months after
      the disaster by standardized instruments. RESULTS: Of the evacuated sample, 13%
      met DSM-IV criteria for PTSD in contrast to 1% in the control group; 35% of the
      exposed sample and 7% of the control group were identified as 'probable cases' by
      the GHQ-30 (both p's < 0.0005). CONCLUSION: The study provides evidence of the
      negative impact of a technological disaster on mental health and the need of
      preventive interventions.

PMID- 17516013
TI  - Prevalence of mental disorders based on general population surveys.
AB  - OBJECTIVE: In the last two decades, a multitude of investigations into the
      frequency of mental disorders in the population have emerged, making it difficult
      to keep track of recent findings and tasks. Building on a historical review, the
      present study provides a comprehensive overview of knowledge about the prevalence
      of mental disorders. METHOD: The review is based on current national surveys with
      comparable methodology. Study selection, based on a consecutive literature search
      through August 2005, led to the inclusion of Australian, German, Dutch and US
      American (NCS; NCS-R) surveys of mental disorders in the general population.
      RESULTS: A considerable proportion of the population is found to have a mental
      disorder. The most frequent disorders within the preceding 12 months are mood
      disorders (6.6-11.9%) and anxiety disorders (5.6-18.1%). Substance disorders (3.8
      11.3%) and somatoform disorders (11.0%) are also very frequent. The prevalence
      rates presented in each survey are dependent on the specific disorders included
      and the classification system underlying them. Important risk factors are being
      female, being unmarried, being unemployed and having a low social status.
      CONCLUSIONS: Knowledge about mental disorders in the general population can
      contribute to bringing about considerable improvement in the treatment of mental
      disorders. In addition to available knowledge, however, there is a continued need
      to address existing challenges from both a methodological and content-related
      perspective, e.g. the lack of or inadequate inclusion of specific disorders, the
      lack of prevalence rates of mental disorders in childhood and adolescence, and
      the as yet only rare inclusion of personality disorders.

PMID- 17516014
TI  - Parental psychopathology in child and adolescent obsessive-compulsive disorder.
AB  - PURPOSE: To identify the lifetime prevalence of obsessive-compulsive disorder
      (OCD) and other psychiatric diagnoses in parents of OCD pediatric patients as
      well as the frequency of onset of psychiatric disorders in the 6 months prior to
      evaluation. METHODS: Parents (n = 63) of 32 children and adolescents (20 males
      and 12 females; mean age of 13.3 +/- 2.4) with OCD and parents of (n = 63) 32 age
      and sex-matched controls with no psychiatric diagnosis were examined. The semi
      structured SCID-I was used to identify axis I psychiatric disorders and SCID-II
      to evaluate personality disorders. RESULTS: Mothers of patients had significantly
      more psychiatric diagnoses than control mothers (P = 0.001). Only parents of
      patients had diagnosis of OCD (P = 0.01) and psychiatric diagnosis (Adjustment
      Disorders, Major Depression, Anxiety Disorders) with onset during the 6 months
      prior to evaluation (P = 0.001). The duration of disease in children appeared to
      be related to development of morbidity in parents (P = 0.04). Parents of patients
      also showed a higher incidence of personality disorders (P = 0.01), in particular
      avoidant (6 versus 1 parents, P < 0.055) and obsessive-compulsive (9 versus 2
      parents, P = 0.016) personality disorders. CONCLUSIONS: The findings suggest that
      there may be an excess of psychopathology in parents of children with OCD as
      compared to parents of pediatric and non-psychiatric patients. Adjustment
      disorders with depressive and anxious symptoms are significantly more frequent in
      mothers of OCD children after the onset of the disease.

PMID- 17516015
TI  - The descriptive epidemiology of internalizing and externalizing psychiatric
      dimensions.
AB  - BACKGROUND: There is a growing recognition that comorbidity among individual
      mental disorders is best explained by the broad, psychiatric dimensions of
      internalization (sub-divided into distress and fear) and externalization. The
      aims of the current study were to examine the descriptive epidemiology of these
      psychiatric dimensions. METHODS: Continuous measures of distress, fear and
      externalization dimensions were obtained from principal components analysis of 11
      common ICD-10 mental disorders in a large (N = 10,641) community sample. The
      relationships between these three dimensions and sociodemographic, physical
      illness and personality disorder characteristics were determined using
      multivariate linear regression analyses. RESULTS: The results suggest that the
      distress dimension is more strongly related to disadvantageous sociodemographic
      characteristics and physical health conditions than either the fear or
      externalizing dimensions. The results also demonstrate some specificity in
      profiles particularly with regard to the personality disorders. CONCLUSIONS:
      Greater emphasis should be placed on continuous psychiatric dimensions that are
      thought to underlie the expression of putatively independent mental disorders.

PMID- 17516016
TI  - Self-harm in England: a tale of three cities. Multicentre study of self-harm.
AB  - BACKGROUND: Self-harm is a major healthcare problem in the United Kingdom, but
      monitoring of hospital presentations has largely been done separately in single
      centres. Multicentre monitoring of self-harm has been established as a result of
      the National Suicide Prevention Strategy for England. METHOD: Data on self-harm
      presentations to general hospitals in Oxford (one hospital), Manchester (three
      hospitals) and Leeds (two hospitals), collected through monitoring systems in
      each centre, were analysed for the 18-month period March 2000 to August 2001.
      RESULTS: The findings were based on 7344 persons who presented following 10,498
      episodes of self-harm. Gender and age patterns were similar in the three centres,
      57.0% of patients being female and two-thirds (62.9%) under 35 years of age. The
      largest numbers by age groups were 15-19 year-old females and 20-24 year-old
      males. The female to male ratio decreased with age. Rates of self-harm were
      higher in Manchester than Oxford or Leeds, in keeping with local suicide rates.
      The proportion of patients receiving a specialist psychosocial assessment varied
      between centres and was strongly associated with admission to the general
      hospital. Approximately 80% of self-harm involved self-poisoning. Overdoses of
      paracetamol, the most frequent method, were more common in younger age groups,
      antidepressants in middle age groups, and benzodiazepines and sedatives in older
      age groups. Alcohol was involved in more than half (54.9%) of assessed episodes.
      The most common time of presentation to hospital was between 10 pm and 2 am.
      CONCLUSIONS: Multicentre monitoring of self-harm in England has demonstrated
      similar overall patterns of self-harm in Oxford, Manchester and Leeds, with some
      differences reflecting local suicide rates. Diurnal variation in time of
      presentation to hospital and the need for assessment of non-admitted patients
      have implications for service provision.

PMID- 17516017
TI  - Immunohistochemical identification of decorin and biglycan in human dentin: a
      correlative field emission scanning electron microscopy/transmission electron
      microscopy study.
AB  - Decorin and biglycan, two small leucine-rich proteoglycans, have been proposed to
      play important roles in matrix-mediated formation of mineralized tissues, and
      their three-dimensional arrangement in human dentin is still not completely
      understood. The aim of this study was to immunohistochemically analyze the
      distribution of decorin and biglycan in human predentin/dentin organic matrix
      under a high-resolution field emission in-lens scanning electron microscope (FEI
      SEM) and a transmission electron microscope (TEM). Tooth dentin specimens were
      submitted to either a preembedding or a postembedding immunolabeling technique
      using primary antibodies antidecorin and antibiglycan and gold-conjugated
      secondary antibodies. Correlative FEI-SEM/TEM observations showed that the two
      antibodies yielded a similar labeling pattern over the processes of odontoblasts
      and the predentin. Decorin and biglycan were mainly associated with the collagen
      fibers within the predentin layer, revealing a moderate immunoreaction that was
      significantly higher compared to the one observed on dentin. Thus, a generally
      weak labeling for decorin was found in dentin, which, however, was significantly
      higher on odontoblast processes within dentinal tubules than in intertubular
      dentin. On the other hand, biglycan immunolocalization on dentin revealed few
      gold particles rather uniformly distributed, without showing significant
      differences between tubular and intertubular regions. In conclusion, this study
      reveals distinct distribution patterns of decorin and biglycan and their relation
      with collagen. Decorin's and biglycan's precise roles within prematrix and
      mineralized matrix in human teeth should be further clarified.

PMID- 17516018
TI  - Loss of sex-specific difference in femoral bone parameters in male leptin
      knockout mice.
AB  - Sex-dependent differences were identified in the femoral bone parameters of male
      and female ob/ob (leptin knockout) mice compared with their C57BL/6 wild-type
      background strain. Total fat, lean weight and body weight were not different
      between adult male and female leptin knockout mice. However, leptin knockout
      males exhibited lower lean weights than C57BL/6 males. Peripheral quantitative
      computerized tomographic measurements at the femoral midshaft revealed that the
      normal differences in the periosteal circumference, endosteal circumference,
      total bone mineral content, and polar moment of inertia normally observed between
      adult male and female wild-type mice were lost between adult male and female
      ob/ob mice. Significant reductions in these bone parameters were seen in male
      ob/ob mice compared to male wild-type mice but not in female ob/ob mice compared
      to female wild-type mice. In prepubertal mice, there were no differences in
      phenotype and femoral bone parameters between males and females within any
      strain, suggesting sex hormone functions. Serum free testosterone levels were 5.6
      fold higher in adult male ob/ob mice than in adult male C57BL/6 wild-type mice,
      and serum estradiol levels were 1.8- and 1.3-fold greater in adult male and
      female ob/ob mice, respectively, than in their wild-type counterparts. Androgen
      receptor gene expression was not different in femur-derived bone cells of male
      ob/ob mice compared with wild-type mice. The loss of sex-related differences in
      these bone parameters in adult male ob/ob mice might result from deficient
      signaling in the androgen signaling pathway and the fact that leptin functions
      are permissive for androgen effects on bone development.

PMID- 17516019
TI  - Claudin-8 expression in renal epithelial cells augments the paracellular barrier
      by replacing endogenous claudin-2.
AB  - Claudins are transmembrane proteins of the tight junction that determine and
      regulate paracellular ion permeability. We previously reported that claudin-8
      reduces paracellular cation permeability when expressed in low-resistance Madin
      Darby canine kidney (MDCK) II cells. Here, we address how the interaction of
      heterologously expressed claudin-8 with endogenous claudin isoforms impacts
      epithelial barrier properties. In MDCK II cells, barrier improvement by claudin-8
      is accompanied by a reduction of endogenous claudin-2 protein at the tight
      junction. Here, we show that this is not because of relocalization of claudin-2
      into the cytosolic pool but primarily due to a decrease in gene expression.
      Claudin-8 also affects the trafficking of claudin-2, which was displaced
      specifically from the junctions at which claudin-8 was inserted. To test whether
      replacement of cation-permeable claudin-2 mediates the effect of claudin-8 on the
      electrophysiological phenotype of the host cell line, we expressed claudin-8 in
      high-resistance MDCK I cells, which lack endogenous claudin-2. Unlike in MDCK II
      cells, induction of claudin-8 in MDCK I cells (which did not affect levels of
      endogenous claudins) did not alter paracellular ion permeability. Furthermore,
      when endogenous claudin-2 in MDCK II cells was downregulated by epidermal growth
      factor to create a cell model with low transepithelial resistance and low levels
      of claudin-2, the permeability effects of claudin-8 were also abolished. Our
      findings demonstrate that claudin overexpression studies measure the combined
      effect of alterations in both endogenous and exogenous claudins, thus explaining
      the dependence of the phenotype on the host cell line.

PMID- 17516020
TI  - Fractures during growth: potential role of a milk-free diet.
AB  - Dietary calcium deficiency may increase fracture risk. In girls, 29.4% of
      fracture cases and 11.8% of controls without fracture had a history of milk-free
      diet. The odds ratio (OR) for fracture with a milk-free diet in girls was 4.6, p
      < 0.01. In boys, 23% of cases and 19% of controls had a history of a milk-free
      diet; OR = 1.3, NS). A milk-free diet due to cow's milk allergy is associated
      with increased fracture risk in girls. INTRODUCTION: An intake of calcium below
      the reference daily intake (RDI) of 800-1200 mg/day during growth is thought to
      increase fracture risk even though convincing evidence for this view is scarce.
      The paucity of evidence may be partly due to many trial participants being
      calcium replete. Children and adolescents with cow's milk allergy (CMA) avoid
      milk and have a calcium intake below the RDI. The aim of this study was to
      examine the association between consumption of a milk-free diet and fracture
      risk. METHODS: In this case-control study conducted in Poland, 57 boys and 34
      girls aged 2.5-20 years with fractures (cases) were randomly matched by age and
      sex with 171 boys and 102 girls without fractures (controls). Weight and height
      were examined using standard methods. Bone mineral density (BMD) and body
      composition were measured using dual-energy X-ray absorptiometry. Conditional
      logistic regression and Bayesian analyses were used to determine the proportion
      of the fracture risk attributable to a milk-free diet. RESULTS: In girls, 29.4%
      of cases and 11.8% of controls had a history of milk-free diet producing an odds
      ratio (OR) for fracture associated with a milk-free diet of 4.6 (95% confidence
      interval [CI]: 1.4-15.5, p < 0.01). In boys, 23% of cases and 19% of controls had
      a history of a milk-free diet; OR = 1.3 (95% CI: 0.6-2.7, NS). If the prevalence
      of CMA in the population is 5%, only 6.7% of the fractures occurring are
      attributable to CMA and the associated nutritional deficit. CONCLUSIONS: Cow's
      milk allergy is associated with increased fracture risk in girls. Whether this
      association is due to the illness, calcium deficit or a deficit in other milk
      nutrients is uncertain. These data suggest that the contribution of milk-free
      diet to fracture liability among children and adolescents is modest.

PMID- 17516021
TI  - A computer-based measure of irregularity in vertebral alignment is a BMD
      independent predictor of fracture risk in postmenopausal women.
AB  - Prevalent fracture and BMD are core elements of fracture prediction. In this
      control study case, we demonstrate that a simple computer-based estimation of
      local irregularities in the alignment of the lumbar vertebrae independently
      contributes to the fracture risk, thus supplementing current diagnostic tools.
      INTRODUCTION: We tested the hypothesis that degree of lordosis and/or
      irregularity in the alignment of lumbar vertebrae could be contributors to the
      risk of fragility fractures. METHODS: This was a case-control analysis including
      144 elderly women; 108 maintaining skeletal integrity, whereas 36 sustaining a
      lumbar vertebral fracture during a 7.5-year observation period. The two groups of
      women were carefully matched for age, BMI, spine BMD and numerous classic risk
      factors. Lateral X-rays of the lumbar spine were digitized and the four corner
      points of endplates on each vertebra from Th12 to L5 were annotated. The degree
      of lordosis and irregularity of vertebral alignment was assessed by image
      analysis software. RESULTS: Degree of lordosis was not predictive for fractures.
      In contrast, irregularity was significantly higher in those who later sustained a
      fracture (1.6 x 10(-2)vs. 2.0 x 10(-3) cm(-1), p < 0.001), and further increased
      upon a sustained fracture (2.8 x 10(-2) cm(-1), p < 0.001), but was unchanged in
      controls (1.6 x 10(-2) cm(-1)). The predictive value of irregularity was
      independent of classic risk factors of fractures, including BMD (p < 0.01).
      CONCLUSION: Our results suggest that the herein introduced simple measure of
      irregularities in vertebral alignment could provide useful supplement to the
      currently used diagnostic tools of fracture prediction in elderly women.

PMID- 17516022
TI  - Zoledronic acid efficacy and safety over five years in postmenopausal
      osteoporosis.
AB  - In a 5-year study involving 119 postmenopausal women, zoledronic acid 4 mg given
      once-yearly for 2, 3 or 5 years was well tolerated with no evidence of excessive
      bone turnover reduction or any safety signals. BMD increased significantly. Bone
      turnover markers decreased from baseline and were maintained within premenopausal
      reference ranges. INTRODUCTION: After completion of the core study, two
      consecutive, 2-year, open-label extensions investigated the efficacy and safety
      of zoledronic acid 4 mg over 5 years in postmenopausal osteoporosis. METHODS: In
      the core study, patients received 1 to 4 mg zoledronic acid or placebo. In the
      first extension, most patients received 4 mg per year and then patients entered
      the second extension and received 4 mg per year or calcium only. Patients were
      divided into three subgroups according to years of active treatment received (2,
      3 or 5 years). Changes in BMD and bone turnover markers (bone ALP and CTX-I) were
      assessed. RESULTS: All subgroups showed substantial increases in BMD and
      decreases in bone markers. By the end of the core study, 37.5% of patients
      revealed a suboptimal reduction (< 30%) of bone ALP levels. After subsequent
      study drug administration during the extensions, there was no evidence of
      progressive reduction of bone turnover markers. Furthermore, increased marker
      levels after treatment discontinuation demonstrates preservation of bone
      remodelling capacity. CONCLUSIONS: This study showed that zoledronic acid 4 mg
      once-yearly was well tolerated and effective in reducing biomarkers over 5 years.
      Detailed analysis of bone marker changes, however, suggests that this drug
      regimen causes insufficient reduction of remodelling activity in one third of
      patients.

PMID- 17516023
TI  - Identification of a novel GPR143 mutation in a large Chinese family with
      congenital nystagmus as the most prominent and consistent manifestation.
AB  - Congenital nystagmus is characterized by involuntary, rhythmical, repeated
      oscillations of one or both eyes. We studied a large Chinese family with
      nystagmus as a prominent and consistent manifestation phenotype in nine patients
      to map and identify a disease-causing gene for nystagmus. X-linked recessive
      inheritance was observed in the family, and foveal hypoplasia was detected in
      some of the nine patients. The disease gene was mapped to an approximately 10.6
      Mb region flanked by DXS996 and DXS7593 on Xp22 with a significant peak
      multipoint LOD score. Analysis of 21 candidate genes in the region revealed a
      novel p.S89F mutation in the second transmembrane domain of GPR143, a G protein
      coupled receptor which causes ocular albinism when mutated. All male patients in
      the family were hemizygous for the mutation; the female carriers were
      heterozygous for the mutation. The p.S89F mutation was not identified in 100
      normal females or 100 normal males. Our results indicate that a mutation in the
      GPR143 gene can cause a variant form of ocular albinism, with congenital
      nystagmus as the most prominent and only consistent finding in all patients in
      this Chinese family. These results expand the spectrum of clinical phenotypes
      associated with GPR143 mutations.

PMID- 17516024
TI  - Dimethylamino-functionalised and N-heteroaryl-substituted titanocene anticancer
      drugs: synthesis and cytotoxicity studies.
AB  - From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different
      lithiated N-heterocyclic compounds (N,N-dimethylaminomethylpyrrole, 1
      methylimidazole and 2,4-[bis(N',N'-dimethylaminomethyl)]-N-methyl pyrrole), the
      corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These
      three lithiated intermediates underwent a transmetallation reaction with TiCl4
      resulting in dimethylamino-functionalised titanocenes 5a-c. When these
      titanocenes were tested against LLC-PK cells, the IC50 values obtained were of
      13, and 63 microM for titanocenes 5b and 5c, respectively. The most cytotoxic
      titanocene in this paper (5a) with an IC50 value of 6.8 microM is found to be
      almost as cytotoxic as cis-platin, which showed an IC50 value of 3.3 microM, when
      tested on the epithelial pig kidney LLC-PK cell line, and titanocene 5c is
      approximately 400 times better than titanocene dichloride itself.

PMID- 17516025
TI  - Isolation and characterization of a metallothionein-1 protein in Chloris virgata
      Swartz that enhances stress tolerances to oxidative, salinity and carbonate
      stress in Saccharomyces cerevisiae.
AB  - Chloris virgata Swartz (C. virgata) is a gramineous wild plant that is found in
      alkaline soil areas in northeast China and is highly tolerant to carbonate
      stress. We constructed a cDNA library from C. virgata seedlings treated with
      NaHCO(3), and isolated a type 1 metallothionein (MT1) gene (ChlMT1: AB294238)
      from the library. The amino acid sequence of ChlMT1 contained 12 cysteine
      residues that constituted the Cys-X-Cys (X = amino acid except Cys) motifs in the
      N- and C-terminal regions. Northern hybridization showed that expression of
      ChlMT1 was induced by several abiotic stresses, from salts (NaCl and NaHCO(3)), a
      ROS inducer (paraquat), and metals (CuSO(4), ZnSO(4), and CoCl(2)). ChlMT1
      expression in leaf was induced by 200 mM NaCl and 100 mM NaHCO(3). About 5 microM
      Paraquat, 500 microM Zn(2+), and 500 microM Co(2+) also induced expression of
      ChlMT1 in leaf after 6 h, and 100 microM Cu(2+) induced it after 24 h.
      Saccharomyces cerevisiae when transformed with the ChlMT1 gene had dramatically
      increased tolerances to salts (NaCl and NaHCO(3)) and ROS.

PMID- 17516026
TI  - Lisosan G, a powder of grain, does not interfere with the drug metabolizing
      enzymes and has a protective role on carbon tetrachloride-induced hepatotoxicity.
AB  - Lisosan G is a powder of grain registered as an alimentary integrator. The
      treatment of rats for 4 days with 0.5 g Lisosan G/kg had no effect on various
      drug metabolizing enzymes. Experiments in vitro showed that Lisosan G had radical
      scavenger activity. A confirmation of the antioxidative property of Lisosan G was
      also confirmed when it was administered in vivo to carbon tetrachloride (CCl(4))
      intoxicated rats. The toxicity caused by CCl(4)-treatment of rats was restored to
      the control levels when the rats were given Lisosan G for 4 days before CCl(4).
      Lisosan G thus does not interfere with drug metabolizing system but has
      antioxidant properties and protects against CCl(4)-induced hepatotoxicity.

PMID- 17516027
TI  - Isolation and characterization of a novel cDNA encoding ERF/AP2-type
      transcription factor OsAP25 from Oryza sativa L.
AB  - Using a yeast one-hybrid method, a transcription factor, OsAP25, which interacts
      specifically with a GCC box was isolated from rice. The OsAP25 protein contained
      a conserved ethylene-responsive element binding factor (ERF) domain which shared
      identity with other reported ERF domains. Phylogenetic analysis showed that
      OsAP25 could be categorized into class III ERF of the previously characterized
      ERF proteins on an evolutionary relationship. The semi-quantitative RT-PCR
      analysis revealed that OsAP25 gene was constitutively expressed in leaves, roots,
      growing points, flower, bolting stage and grain filling stage. In addition,
      OsAP25 gene was induced by NaCl, cold, drought, abscisic acid and exogenous
      ethylene.

PMID- 17516028
TI  - Organotypic distribution of stem cell markers in formalin-fixed brain harboring
      glioblastoma multiforme.
AB  - The role of stem cells in the origin, growth patterns, and infiltration of
      glioblastoma multiforme is a subject of intense investigation. One possibility is
      that glioblastoma may arise from transformed stem cells in the ventricular zone.
      To explore this hypothesis, we examined the distribution of two stem cell
      markers, activating transcription factor 5 (ATF5) and CD133, in an autopsy brain
      specimen from an individual with glioblastoma multiforme. A 41-year-old male with
      a right posterior temporal glioblastoma had undergone surgery, radiation, and
      chemotherapy. The brain was harvested within several hours after death. After
      formalin fixation, sectioning, and mapping of tumor location in the gross
      specimen, histologic specimens were prepared from tumor-bearing and grossly
      normal hemispheres. Fluorescence immunohistochemistry and colorimetric staining
      were performed for ATF5 and CD133. Both markers co-localized to the ependymal and
      subependymal zones on the side of the tumor, but not in the normal hemisphere or
      more rostrally in the affected hemisphere. ATF5 staining was especially robust
      within the diseased hemisphere in histologically normal ependyma. To our
      knowledge, this is the first in situ demonstration of stem cell markers in whole
      human brain. These preliminary results support the hypothesis that some
      glioblastomas may arise from the neurogenic zone of the lateral ventricle. The
      robust staining for ATF5 and CD133 in histologically normal ventricular zone
      suggests that an increase in periventricular stem cell activity occurred in this
      patient on the side of the tumor, either as a localized response to brain injury
      or as an integral component of oncogenesis and tumor recurrence.

PMID- 17516029
TI  - Direct determination of the stereoisomeric composition of callosobruchusic acid,
      the copulation release pheromone of the azuki bean weevil, Callosobruchus
      chinensis L., by the 2D-Ohrui-Akasaka method.
AB  - The stereoisomeric composition of the copulation release pheromone of the azuki
      bean weevil, Callosobruchus chinensis L., was determined to be R:S=3.3-3.4:1 by
      the 2D-Ohrui-Akasaka method.

PMID- 17516030
TI  - CDK11(p58) protein kinase activity is associated with Bcl-2 down-regulation in
      pro-apoptosis pathway.
AB  - CDK11(p58), a G2/M-specific protein kinase, has been shown to be associated with
      apoptosis in many cell lines, with largely unknown mechanisms. Our previous study
      proved that CDK11(p58)-enhanced cycloheximide (CHX)-induced apoptosis in SMMC
      7721 hepatocarcinoma cells. Here we report for the first time that ectopic
      expression of CDK11(p58) down-regulates Bcl-2 expression and its Ser70, Ser87
      phosphorylation in CHX-induced apoptosis in SMMC-7721 cells. Overexpression of
      Bcl-2 counteracts the pro-apoptotic activity of CDK11(p58). Furthermore, we
      confirm that the kinase activity of CDK11(p58) is essential to the down
      regulation of Bcl-2 as well as apoptosis. Taken together, these results
      demonstrate that CDK11(p58) down-regulates Bcl-2 in pro-apoptosis pathway
      depending on its kinase activity, which elicits survival signal in
      hepatocarcinoma cells.

PMID- 17516031
TI  - alpha-Thrombin inhibits DNA synthesis in rat hepatocytes but not in hepatoma
      cells by receptor activation and proteolysis.
AB  - Prothrombin is a plasma protein, which after tissue injury is converted to alpha
      thrombin and is mainly involved in blood clot formation. It has also been shown
      to have a mitogenic effect on primary endothelial cells, vascular smooth muscle
      cells, fibroblasts and some tumor cells, but is an inhibitor of rat hepatocyte
      DNA synthesis on fibronectin matrix in cell culture. We now report that
      prothrombin is converted to alpha-thrombin by primary cultures of normal adult
      rat hepatocytes and alpha-thrombin is also a potent inhibitor of hepatocytes DNA
      synthesis. In contrast, rat hepatoma cells cultured under similar conditions were
      resistant to alpha-thrombin mediated DNA synthesis inhibition. The inhibitory
      effect of alpha-thrombin on DNA synthesis was antagonized by hirudin and
      antithrombin, two specific alpha-thrombin inhibitors or by the presence of
      collagen-I matrix. A thrombin receptor activating peptide (TRAP6) also inhibited
      EGF-mediated rat hepatocyte DNA synthesis, suggesting a role of the thrombin
      receptors in this process. Matrix fibronectin was degraded by alpha-thrombin.
      However, no appreciable cell detachment was observed. These results suggest a
      role of alpha-thrombin as a potent growth inhibitor of normal hepatocytes,
      possibly through control of fibronectin or other matrix protein(s).

PMID- 17516032
TI  - Mutations in SIRT2 deacetylase which regulate enzymatic activity but not its
      interaction with HDAC6 and tubulin.
AB  - Human SIRT2 is a cytoplasmic NAD-dependent deacetylase implicated in the mitotic
      regulation of microtubule dynamics by its association with the class II histone
      deacetylase 6 (HDAC6). We have previously reported that SIRT2 is multiply
      phosphorylated in a cell cycle dependent pattern. Here, we demonstrate that HDAC6
      binds to both phosphorylated and unphosphorylated forms of SIRT2 and that tubulin
      binds only to the SIRT2-HDAC6 complex. Tubulin does not bind to either HDAC6 or
      SIRT2 individually. In addition, we show that replacement of specific serines
      with alanines in either isoform of SIRT2 regulates its enzymatic activity. We
      also found that overexpression of isoform2 was deleterious to cell survival.
      SIRT2 was found to be phosphorylated at serines 368 and 372, outside the
      conserved core domain of the Sir2 protein family. Double replacement of S368A and
      S372A reduced SIRT2 deacetylase activity by 44% compared to wildtype activity.
      Replacements of other serine, threonine, and tyrosine residues, which did not
      alter the phosphorylation pattern, had varying effects on SIRT2 deacetylase
      activity but no effect on tubulin/HDAC6 binding.

PMID- 17516033
TI  - Time course of changes in the expression of DHPR, RyR(2), and SERCA2 after
      myocardial infarction in the rat left ventricle.
AB  - Postinfarction left ventricular remodeling leads to the functional decline of the
      left ventricle (LV). Since dihydropyridine receptor (DHPR), ryanodine receptor
      (RyR(2)), and sarco-endoplasmic reticulum (SR) Ca(2+)-ATPase2 (SERCA2a) play a
      major role in the contractility of the heart, the aim of our study was to
      evaluate the time course of changes in the expression of these proteins 1 day, 2
      weeks and 4 weeks after myocardial infarction (MI). Myocardial infarction was
      produced by ligation of left anterior descending coronary artery of the rat.
      Transthoracic echocardiography was performed to characterize structural and
      functional changes after MI. To evaluate protein mRNA levels and the relative
      amount of proteins, real-time quantitative RT-PCR and Western blotting were used.
      LV ejection fraction and fractional shortening decreased significantly during the
      4-week follow-up period (P < 0.001). Typical features of LV remodeling after MI
      were seen, with a decrease in anterior wall thickness (P < 0.001) and dilatation
      of the LV (P < 0.001). Expression of DHPR and RyR(2) mRNAs decreased and Serca2a
      mRNA tended to decrease 1 day after MI (P < 0.001, P < 0.01 and P = 0.06,
      respectively), followed by recovery of the expression during the next 4 weeks. In
      the infarcted hearts the quantities of SERCA2 proteins in the LV were
      significantly decreased at the time of 4 weeks. In conclusion, MI was associated
      with transient decrease in the expression of the DHPR and RyR(2) mRNAs and a
      reduced quantity of SERCA2 proteins in the LV. Since they have a key role in the
      contraction of the heart, changes in the expression of these proteins may be
      important regulators of LV systolic function after MI.

PMID- 17516034
TI  - Neutralization of animal virus infectivity by antibody.
AB  - Neutralization is the ability of antibody to bind to and inactivate virus
      infectivity under defined conditions in vitro. Most neutralizing antibodies also
      protect animals in vivo, but protection is more complex as it also involves
      interaction of antibody with cells and molecules of the innate immune system.
      Neutralization by antibody can be mediated by a number of different mechanisms:
      by aggregation of virions, destabilization of the virion structure, inhibition of
      virion attachment to target cells, inhibition of the fusion of the virion lipid
      membrane with the membrane of the host cell, inhibition of the entry of the
      genome of non-enveloped viruses into the cell cytoplasm, inhibition of a function
      of the virion core through a signal transduced by an antibody, transcytosing IgA,
      and binding to nascent virions to block their budding or release from the cell
      surface. The mechanism of neutralization is determined by the properties of both
      a virion epitope and the antibody that reacts with it. Further, since a virus has
      at least several unique epitopes sited in different locations on the virion, and
      since the paratope and other properties of the reacting antibody can vary, this
      means that a virus can be neutralized by several different mechanisms.
      Understanding the processes of neutralization informs the creation of modern
      vaccines, and gives valuable insights into virus-cell interactions.

PMID- 17516035
TI  - Co-infection with different subtypes of feline immunodeficiency virus can
      complicate subtype assignment by phylogenetic analysis.
AB  - Phylogenetic analyses of the V3-V5 region of the env gene are used to determine
      Feline immunodeficiency virus (FIV) subtypes but can be complicated by co
      infection with different subtypes or the presence of recombinant subtypes. FIV in
      blood samples from 30 domestic cats in New Zealand was subtyped by sequencing
      three overlapping fragments of the V3-V5 region of the env gene and 467 bp of the
      gag gene. Phylogenetic analyses revealed that the isolates clustered with subtype
      A and C viruses. Seven samples showed discrepancies in subtype assignment from
      analyses of their env gene sequences. Nucleotide differences of 19.6% and 20.9%
      in overlapping regions in two cats suggest co-infection with subtypes A and C.

PMID- 17516038
TI  - [Bedside thrombelastography. Cost reduction in cardiac surgery].
AB  - BACKGROUND: Demographic changes and aggressive medication with platelet
      aggregation inhibitors have resulted in a marked increase in blood and
      coagulation product expenditure and costs in cardiac surgery. We analyzed the
      bedside coagulation test (ROTEM) in order to verify clot forming quality and to
      find a cost-effective treatment algorithm. PATIENTS AND METHODS: Annual treatment
      costs of all cardiosurgical patients were retrospectively analyzed before (729
      patients) and after (693 patients) implementation of the bedside ROTEM test.
      Cumulative numbers and costs of platelet concentrates (PltC), fresh frozen plasma
      (FFP), red blood cell units (RBC), and the coagulation factors prothrombin
      complex concentrates (PCC), recombinant factor VIIa (rFVIIa), factor XIII
      (FXIII), and fibrinogen were assessed. Average monthly numbers and costs were
      compared. The number of rethoracotomies and early mortality were assessed and
      compared in both periods. RESULTS: After ROTEM implementation cumulative RBC
      expenditure showed a 25% decrease and PltC a 50% decrease. FFP expenditure
      remained unchanged. PCC, FXIII were markedly reduced (-80%) while rFVIIa was
      entirely omitted. Fibrinogen, however, showed a two-fold increase. Cumulative
      average monthly costs of all blood products decreased from 66,000 EUR to 45,000
      EUR (-32%). Coagulation factor average monthly costs decreased from 60,000 EUR to
      30,000 EUR (-50%) yielding combined savings of 44%. In contrast, average monthly
      costs for ROTEM were 1,580 EUR. The total number of rethoracotomies decreased
      from 6.6% to 5.5% while early mortality (5.9%; 6.0%) remained stable.
      CONCLUSIONS: Cumulative costs for treatment of perioperative coagulation
      disorders were reduced by bedside ROTEM analysis to achieve a selective
      substitution management. Saved costs for blood and coagulation products clearly
      outweighed the expenses of ROTEM. Adequate differential coagulation management
      can therefore be cost-effective.

PMID- 17516039
TI  - [Estimates by the surgeon in relation to fast-track concepts in intestinal
      surgery: commentary on the contribution of Hasenberg et al. (2007)].

PMID- 17516040
TI  - [A survey of perioperative therapy for elective colon resection in Germany,
      2006].
AB  - BACKGROUND: Despite the evidence that fast-track concepts in colon surgery lead
      to an enhanced recovery rate, there is no information on the prevalence and
      utilization of such programs in Germany. METHODS: Based on a conventional sigmoid
      resection, we asked 1,270 surgical departments in Germany to describe their
      standard surgical procedures in a questionnaire. RESULTS: The response rate was
      385 (30.31%). A total of 96% use a bowel preparation, 83% a vertical incision,
      10% use a nasogastric decompression for longer then 1 day, 34% avoid intra
      abdominal drains, 51% allow clear fluids on the day of surgery, 13% offer solid
      food on the first day after surgery, 75% use epidural analgesia and 47% discharge
      the patients by the seventh day after surgery. CONCLUSION: Although there is an
      evident benefit using fast-track concepts, they are not yet in wide use as a
      standard procedure. Further efforts have to be made to ensure that the majority
      of patients will benefit from these concepts.

PMID- 17516041
TI  - [Squamous cell carcinoma of the head and neck. Photodynamic therapy with Foscan].
AB  - INTRODUCTION: Photodynamic therapy (PDT) is a relatively new method of treating
      superficial tumours of the skin or mucous membranes. After the injection of a
      photosensitiser, the tumour area is exposed to non-thermal laser light. This
      causes a phototoxic reaction, producing oxygen radicals that destroy the tumour
      cells. PATIENTS AND METHODS: From November 2004 to February 2006, a total of 24
      patients with recurrent or secondary tumours after squamous cell carcinoma of the
      head and neck were treated with PDT at the German Armed Forces Hospital in Ulm
      after other treatment options had failed. Meta-tetrahydroxyphenyl chlorin
      (mTHPC), known under the trade name of Foscan, was used as the photosensitising
      agent. RESULTS: Complete remission was observed in 12 patients (50%) and partial
      remission was seen in nine (37.5%). Three patients did not respond to treatment.
      The mean duration of overall survival was 305.7 days (+/-199.4) after completion
      of treatment. The mean duration of recurrence-free survival was 302.7 days (+/
      144.9) for patients with complete remission. There were no serious complications.
      CONCLUSIONS: Photodynamic therapy is an important treatment option for patients
      who develop recurrent or secondary tumours after squamous cell carcinoma of the
      upper aerodigestive tract and fail to respond to other treatments. In addition,
      PDT may play a role in the primary treatment of superficial tumours of the oral
      cavity, pharynx and larynx in the future.

PMID- 17516042
TI  - [Progressive muscle atrophy. A rarely diagnosed variant of amyotrophic lateral
      sclerosis].
AB  - Progressive muscle atrophy (PMA) is a degenerative disease of the lower motor
      neuron. The course of the illness and the fatal prognosis correspond to those of
      amyotrophic lateral sclerosis (ALS). Neuropathologic and genetic findings support
      categorizing PMA within the spectrum of ALS, even though no clinical sign of a
      disorder of the upper motor neuron is demonstrable. The diagnosis of PMA is based
      on advanced extremity pareses and atrophies with a high progression rate.
      Respiratory insufficiency is determinative of the prognosis. Absent or late
      affection of bulbar functions is characteristic of the disease. Intraneuronal
      bunina bodies and ubiquitine-positive inclusions, which are established
      morphologic characteristics of ALS, are found post mortem. The treatment options
      of riluzol medication, respiratory therapy, and nutrition are analogous to those
      for typical ALS.

PMID- 17516043
TI  - [Monitoring stroke units: management, outcome, efficiency].
AB  - Treatment of acute stroke in Germany has undergone major changes. To date almost
      half of all stroke patients there are admitted to one of 172 accredited
      monitoring stroke units, 80 of which were classified as inter-regional and 92 as
      regional. Following acute treatment, diagnostic/etiologic work-up and automated
      monitoring of vital functions are performed as well as adapted secondary
      prevention. Another important therapeutic goal includes early rehabilitation.
      International studies have established the superiority of stroke unit treatment
      over conventional care. Although the efficiency of monitoring stroke units in
      Germany was not shown in a randomized study, the prognostic benefit is hardly
      debated anymore. In 2006 a specific procedure standard (OPS) was introduced,
      increasing proceeds to compensate for the higher cost of monitoring and therapy
      but at the same time enforcing strict quality standards.

PMID- 17516044
TI  - Knockout of the gene (ste15) encoding a glycosyltransferase and its function in
      biosynthesis of exopolysaccharide in Streptomyces sp. 139.
AB  - Streptomyces sp. 139 produces a novel exopolysaccharide (EPS) designated Ebosin
      which has antagonistic activity for IL-1R in vitro and remarkable anti-rheumatic
      arthritis activity in vivo. We previously identified a ste (Streptomyces eps)
      gene cluster consisting of 27 ORFs responsible for Ebosin biosynthesis. The gene
      product of ste15 shows high homology to known glycosyltransferases (GTFs). To
      elucidate its function in Ebosin biosynthesis, the ste15 gene was knocked out
      with a double crossover via homologous recombination. Our analysis of
      monosaccharide composition for EPS-m produced by the mutant strain Streptomyces
      sp. 139 (ste15(-)) showed that glucose was significantly diminished compared to
      its natural counterpart Ebosin. This derivative of Ebosin lost the antagonistic
      activity for IL-1R in vitro and its molecular mass was smaller than Ebosin. These
      results have demonstrated that the ste15 gene codes for a GTF for glucose, which
      is functionally involved in Ebosin biosynthesis.

PMID- 17516045
TI  - Detection of chromosomally located and plasmid-borne genes on 20 kb DNA fragments
      in parasporal crystals from Bacillus thuringiensis.
AB  - The association of 20 kb heterologous DNA fragments with the parasporal crystals
      from native and recombinant Bacillus thuringiensis strains was analyzed,
      respectively. The cry2Aa10 gene cloned in plasmid pHC39 was transformed into B.
      thuringiensis subsp. kurstaki strains Cry B and HD73, producing recombinant
      strains Cry B(pHC39) and HD73(pHC39). SDS-PAGE and scanning electron microscopy
      analyses demonstrated that the recombinant Cry B(pHC39) produced cuboidal
      crystals of Cry2Aa10 protoxin, while recombinant HD73(pHC39) produced both
      bipyramidal crystals of Cry1Ac1 protoxin and cuboidal crystals of Cry2Aa10
      protoxin. Bioassay results proved that recombinant HD73(pHC39) showed higher
      insecticidal activity to Helicoverpa armigera than Cry B(pHC39). It was found
      that 20 kb DNA fragments were present in bipyramidal and cuboidal crystals from
      both native and recombinant strains, and the 20 kb heterologous DNAs contained
      chromosome-specific and resident large plasmid-borne DNA fragments, suggesting
      the 20 kb heterologous DNA fragment embodied in crystals came randomly from the
      bacterial chromosomal and plasmid genome. This was the first investigation
      devoted exclusively on the origin of 20 kb DNA fragments in the parasporal
      crystals of B. thuringiensis. The data provides a basis for further investigation
      of the origin of 20 kb DNAs in the crystals and the interaction of DNA and
      protoxins.

PMID- 17516046
TI  - Degradation of beta-hexachlorocyclohexane by haloalkane dehalogenase LinB from
      gamma-hexachlorocyclohexane-utilizing bacterium Sphingobium sp. MI1205.
AB  - The technical formulation of hexachlorocyclohexane (HCH) mainly consists of the
      insecticidal gamma-isomer and noninsecticidal alpha-, beta-, and delta-isomers,
      among which beta-HCH is the most recalcitrant and has caused serious
      environmental problems. A gamma-HCH-utilizing bacterial strain, Sphingobium sp.
      MI1205, was isolated from soil which had been contaminated with HCH isomers. This
      strain degraded beta-HCH more rapidly than the well-characterized gamma-HCH
      utilizing strain Sphingobium japonicum UT26. In MI1205, beta-HCH was converted to
      2,3,5,6-tetrachlorocyclohexane-1,4-diol (TCDL) via 2,3,4,5,6
      pentachlorocyclohexanol (PCHL). A haloalkane dehalogenase LinB (LinB(MI)) that is
      98% identical (seven amino-acid differences among 296 amino acids) to LinB from
      UT26 (LinB(UT)) was identified as an enzyme responsible for the two-step
      conversion of beta-HCH to TCDL. This property of LinB(MI) contrasted with that of
      LinB(UT), which catalyzed only the first step conversion of beta-HCH to PCHL.
      Site-directed mutagenesis and computer modeling suggested that two of the seven
      different amino acid residues (V134 and H247) forming a catalytic pocket of LinB
      are important for the binding of PCHL in an orientation suitable for the reaction
      in LinB(MI). However, mutagenesis also indicated the involvement of other
      residues for the activity unique to LinB(MI). Sequence analysis revealed that
      MI1205 possesses the IS6100-flanked cluster that contains two copies of the linB
      (MI) gene. This cluster is identical to the one located on the exogenously
      isolated plasmid pLB1, suggesting that MI1205 had recruited the linB genes by a
      horizontal transfer event.

PMID- 17516047
TI  - Thiosulfate oxidation by a moderately thermophilic hydrogen-oxidizing bacterium,
      Hydrogenophilus thermoluteolus.
AB  - The moderately thermophilic Betaproteobacterium, Hydrogenophilus thermoluteolus,
      not only oxidizes hydrogen, the principal electron donor for growth, but also
      sulfur compounds including thiosulfate, a process enabled by sox genes. A
      periplasmic extract of H. thermoluteolus showed significant thiosulfate oxidation
      activity. Ten genes apparently involved in thiosulfate oxidation (soxEFCDYZAXBH)
      were found on a 9.7-kb DNA fragment of the H. thermoluteolus chromosome. The
      proteins SoxAX, which represent c-type cytochromes, were co-purified from the
      cells of H. thermoluteolus; they enhanced the thiosulfate oxidation activity of
      the periplasmic extract when added to the latter.

PMID- 17516048
TI  - A cold-adapted esterase from psychrotrophic Pseudoalteromas sp. strain 643A.
AB  - A psychrotrophic bacterium producing a cold-adapted esterase upon growth at low
      temperatures was isolated from the alimentary tract of Antarctic krill Euphasia
      superba Dana, and classified as Pseudoalteromonas sp. strain 643A. A genomic DNA
      library of strain 643A was introduced into Escherichia coli TOP10F', and
      screening on tributyrin-containing agar plates led to the isolation of esterase
      gene. The esterase gene (estA, 621 bp) encoded a protein (EstA) of 207 amino acid
      residues with molecular mass of 23,036 Da. Analysis of the amino acid sequence of
      EstA suggests that it is a member of the GDSL-lipolytic enzymes family. The
      purification and characterization of native EstA esterase were performed. The
      enzyme displayed 20-50% of maximum activity at 0-20 degrees C. The optimal
      temperature for EstA was 35 degrees C. EstA was stable between pH 9 and 11.5. The
      enzyme showed activity for esters of short- to medium-chain (C(4) and C(10))
      fatty acids, and exhibited no activity for long-chain fatty acid esters like that
      of palmitate and stearate. EstA was strongly inhibited by phenylmethylsulfonyl
      fluoride, 2-mercaptoethanol, dithiothreitol and glutathione. Addition of selected
      divalent ions e.g. Mg(2+), Co(2+) and Cu(2+) led to the reduction of enzymatic
      activity and the enzyme was slightly activated ( approximately 30%) by Ca(2+)
      ions.

PMID- 17516049
TI  - A new monocupin quercetinase of Streptomyces sp. FLA: identification and
      heterologous expression of the queD gene and activity of the recombinant enzyme
      towards different flavonols.
AB  - The gene queD encoding quercetinase of Streptomyces sp. FLA, a soil isolate
      related to S. eurythermus (T), was identified. Quercetinases catalyze the 2,4
      dioxygenolytic cleavage of 3,5,7,3',4'-pentahydroxyflavone to 2
      protocatechuoylphloroglucinol carboxylic acid and carbon monoxide. The queD gene
      was expressed in S. lividans and E. coli, and the recombinant hexahistidine
      tagged protein (QueDHis(6)) was purified. Several flavonols were converted by
      QueDHis(6), whereas CO formation from the 2,3-dihydroflavonol taxifolin and the
      flavone luteolin were not observed. In contrast to bicupin quercetinases from
      Aspergillus japonicus and Bacillus subtilis, and bicupin pirins showing
      quercetinase activity, QueD of strain FLA is a monocupin exhibiting 35.9%
      sequence identity to the C-terminal domain of B. subtilis quercetinase. Its
      native molecular mass of 63 kDa suggests a multimeric protein. A queD-specific
      probe hybridized with fragments of genomic DNA of four other quercetin degrading
      Streptomyces strains, but not with DNA of B. subtilis. Potential ORFs upstream of
      queD probably code for a serine protease and an endoribonuclease; two ORFs
      downstream of queD may encode an amidohydrolase and a carboxylesterase. This
      arrangement suggests that queD is not part of a catabolic gene cluster.
      Quercetinases might play a major role as detoxifying rather than catabolic
      enzymes.

PMID- 17516050
TI  - Purification, characterization and gene cloning of isoeugenol-degrading enzyme
      from Pseudomonas putida IE27.
AB  - An isoeugenol-degrading enzyme was purified to homogeneity from Pseudomonas
      putida IE27, an isoeugenol-assimilating bacterium. The purified enzyme was a 55
      kDa monomer and catalyzed the initial step of isoeugenol degradation, the
      oxidative cleavage of the side chain double-bond of isoeugenol, to form vanillin.
      Another reaction product of isoeugenol degradation besides vanillin was
      identified to be acetaldehyde. The values of Km and k (cat) for isoeugenol were
      175 muM and 5.18 s(-1), respectively. The purified enzyme catalyzed the
      incorporation of an oxygen atom from either molecular oxygen or water into
      vanillin, suggesting that the isoeugenol-degrading enzyme is a kind of
      monooxygenase. The gene encoding the isoeugenol-degrading enzyme and its flanking
      regions were isolated from P. putida IE27. The amino acid sequence of the enzyme
      was similar to those of lignostilbene-alpha,beta-dioxygenases, carotenoid
      monooxygenases and 9-cis-epoxycarotenoid dioxygenases.

PMID- 17516051
TI  - Determination of acetone in seawater using derivatization solid-phase
      microextraction.
AB  - Acetone plays an important role in the chemistry of both the atmosphere and the
      ocean, due to its potential effect on the tropospheric HO(x) (= HO + HO(2))
      budget, as well as its environmental and health effects. We discuss the
      development of a mobile, sensitive, selective, economical and facile method for
      the determination of acetone in seawater. The method consists of derivatizing
      acetone to its pentafluorobenzyl oxime using 1,2,3,4,5
      pentafluorobenzylhydroxylamine (PFBHA), followed by solid-phase microextraction
      (SPME) and analysis by gas chromatography/mass spectrometry (GC/MS). A detection
      limit of 3.0 nM was achieved. The buffering capacity of seawater imposes
      challenges in using the method's optimum pH (3.7) on seawater samples, requiring
      calibration standards to be made in buffered salt water and the acidification of
      seawater samples and standards prior to extraction. We employed the technique for
      analysis of selected surface seawater samples taken on the Nordic seas during the
      ARK-XX/1 cruise (R.V. Polarstern). An upper limit of 5.5-9.6 nM was observed for
      acetone in these waters, the first acetone measurements reported for far North
      Atlantic and Arctic waters. Simplified schematic of transformations of organic
      compounds at the atmosphere-ocean interface.

PMID- 17516052
TI  - Procedures for monitoring recombinant erythropoietin and analogues in doping
      control.
AB  - The present report summarizes the main analytical strategies developed to
      identify the presence of recombinant erythropoietin (EPO) administered as a
      doping agent. Indirect evidence is based on the analysis of blood parameters
      (haemoglobin, haematocrit, reticulocytes, macrocytes, etc.) and serum markers
      (concentration of EPO and serum transferrin receptors, etc.). The problem of
      intertechnique comparison for reliable results evaluation is emphasized,
      especially for serum markers. Charge differences between isoforms of recombinant
      EPO and native urinary EPO are the grounds for the isoelectric focusing-double
      blotting-chemiluminescence detection method presently approved for doping
      control. Works addressing its advantages and limitations are presented and
      commented on. The chemical bases of the differential detection are highlighted
      and some future approaches for detection are also presented. The appearance and
      detectability of EPO analogues and mimetics susceptible for abuse are also
      addressed.

PMID- 17516053
TI  - Teaching chemometrics.

PMID- 17516054
TI  - Analytical investigations of poly(acrylic acid) coatings electrodeposited on
      titanium-based implants: a versatile approach to biocompatibility enhancement.
AB  - A polyacrylic acid film was synthesized on titanium substrates from aqueous
      solutions via an electroreductive process for the first time. This work was done
      in order to develop a versatile coating for titanium-based orthopaedic implants
      that acts as both an effective bioactive surface and an effective anti-corrosion
      barrier. The chemical structure of the PAA coating was investigated by X-ray
      photoelectron spectroscopy (XPS). Scanning electron microscopy (SEM) was employed
      to evaluate the effect of annealing treatment on the morphology of the coatings
      in terms of their uniformity and porosity. Inductively coupled plasma mass
      spectrometry was used to measure ion concentrations in ion release tests
      performed on Ti-6Al-4V sheets modified with PAA coatings (annealed and
      unannealed). Results indicate that the annealing process produces coatings that
      possess considerable anti-corrosion performance. Moreover, the availability and
      the reactivity of the surface carboxylic groups were exploited in order to graft
      biological molecules onto the PAA-modified titanium implants. The feasibility of
      the grafting reaction was tested using a single aminoacid residue. A fluorinated
      aminoacid was selected, and the grafting reaction was monitored both by XPS,
      using fluorine as a marker element, and via quartz crystal microbalance (QCM)
      measurements. The success of the grafting reaction opens the door to the
      synthesis of a wide variety of PAA-based coatings that are functionalized with
      selected bioactive molecules and promote positive reactions with the biological
      system interfacing the implant while considerably reducing ion release into
      surrounding tissues.

PMID- 17516055
TI  - Attention influences the excitability of cortical motor areas in healthy humans.
AB  - We investigated whether human attentional processes influence the size of the
      motor evoked potentials (MEP) facilitation and the duration of the cortical
      silent period (CSP) elicited by high-frequency repetitive transcranial magnetic
      stimulation (rTMS). In healthy subjects we assessed the effects of 5 Hz-rTMS,
      delivered in trains of 10 stimuli at suprathreshold intensity over the hand motor
      area, on the MEP size and CSP duration in different attention-demanding
      conditions: "relaxed," "target hand," and "non-target hand" condition. We also
      investigated the inhibitory effects of 1 Hz-rTMS conditioning to the premotor
      cortex on the 5 Hz-rTMS induced MEP facilitation. F-waves evoked by ulnar nerve
      stimulation were also recorded. rTMS trains elicited a larger MEP size
      facilitation when the subjects looked at the target hand whereas the increase in
      CSP duration during rTMS remained unchanged during the three attention-demanding
      conditions. The conditioning inhibitory stimulation delivered to the premotor
      cortex decreased the MEP facilitation during the "target hand" condition, leaving
      the MEP facilitation during the other conditions unchanged. None of the
      attentional conditions elicited changes in the F wave. In healthy subjects
      attentional processes influence the size of the MEP facilitation elicited by high
      frequency rTMS and do so through premotor-to-motor connections.

PMID- 17516056
TI  - Dissociation of nociceptive modulation of a human jaw reflex from the influence
      of stress.
AB  - In human beings, inhibitory jaw reflexes can be depressed by painful stimulation
      of remote parts of the body. Since similar effects can be produced by the stress
      of anticipating pain, we wished to investigate whether the effects of remote
      painful stimuli are dependent on stress. EMG recordings were made from a masseter
      muscle while subjects maintained activity in the muscle at approximately 12.5% of
      maximum using visual feedback. The protocols involved three sequences: (1)
      "standard controls" in which reflexes were evoked by electrical test stimuli
      applied to the upper lip; (2) "standard conditioning" in which painful electrical
      conditioning stimuli were applied over the sural nerve 100 ms before the test
      stimuli; (3) "random sequences" in which test-only and conditioning-test
      combinations were employed in a double-blind, random, order. Data are presented
      as means +/- SEMs. In the standard controls, the stimuli evoked clear inhibitory
      reflexes (latency 37 +/- 1.3 ms, duration 62 +/- 5.6 ms; n = 10) in all the
      subjects. During standard conditioning, the reflex magnitude was reduced
      significantly (by 50.0 +/- 8.5%, P = 0.0002, one-sample t-test). When the test
      only and conditioning-test responses were extracted from the random sequences,
      there was also a significant reduction in the reflex magnitude following
      conditioning (by 34.6 +/- 5.5%, P = 0.0002, one-sample t-test) albeit less so
      than between the standard sequences (P = 0.03, paired t-test). A second series of
      experiments suggested that these lesser effects during the random sequences were
      not substantially due to any loss of temporal summation of the conditioning
      mechanisms. The evidence for this was that application of pairs of conditioning
      stimuli did not produce a significantly greater effect than single conditioning
      stimuli within a random sequence (39.9 +/- 9.6% as opposed to 32.7 +/- 9.1%
      reductions in the reflex, P = 0.117, paired t-test). Therefore since any stress
      in the random sequences would not have been "tied" to the conditioned responses
      alone, the effects of remote painful stimuli on this inhibitory jaw reflex cannot
      be entirely secondary to stress.

PMID- 17516057
TI  - Saccades to the seeing visual hemifield in hemidecorticate patients exhibit task
      dependent reaction times and hypometria.
AB  - In three patients who had one cortical hemisphere removed surgically
      (hemidecortication), we studied visually-triggered saccades directed
      contralateral to the intact cortical hemisphere (i.e., ipsilesional saccades).
      Both saccade reaction times (SRTs) and accuracy of these saccades have been
      reported as abnormal in hemidecorticate patients, but not monkeys. One
      explanation for this difference is that deficits in hemidecorticate patients may
      not have been directly caused by removal of cortical oculomotor structures
      themselves, but may have been a manifestation of compensatory strategies used to
      cope with contralesional hemianopia. We hypothesized that deficits in saccade
      performance to the ipsilesional (seeing) visual hemifield would be directly
      linked to how easily patients could localize targets in their blind hemifield
      with searching saccades. To test this hypothesis, we examined how deficits in our
      patients varied when targets were: (1) randomly presented to either the seeing or
      blind hemifield for long durations thereby permitting searching saccades in the
      blind hemifield; (2) presented as in Experiment 1, but briefly flashed thereby
      removing visual feedback prior to saccade onset thereby rendering searching
      saccades useless; (3) briefly flashed as in Experiment 2, but at random locations
      in only the seeing hemifield (blind hemifield irrelevant). Mean SRTs to the
      seeing hemifield were 165 ms longer than normal in Experiment 2, but only about
      40 ms longer in Experiments 1 and 3. Saccade accuracy was characterized by task
      dependent hypometria in all three experiments with a mean undershoot of about
      twice the amplitude variance. The largest undershoots were in Experiments 2 and
      3. Our data suggest that deficits resulted from the direct effects of the lesions
      themselves coupled with context-dependent strategies used to cope with
      contralesional hemianopia.

PMID- 17516058
TI  - Prehension is really reaching and grasping.
AB  - Prehension has traditionally been seen as the act of coordinated reaching and
      grasping. However, recently, Smeets and Brenner (in Motor Control 3:237-271,
      1999) proposed that we might just as well look at prehension as the combination
      of two independently moving digits. The hand aperture that has featured
      prominently in many studies on prehension, according to Smeets and Brenner's
      "double-pointing hypothesis", is really an emergent property related to the time
      course of the positions of the two digits moving to their respective end points.
      We tested this double-pointing hypothesis by perturbing the end position of one
      of the digits while leaving the end position of the opposing digit unchanged. To
      this end, we had participants reach for and grasp a metallic object of which the
      side surfaces could be made to slide in and out. We administered the perturbation
      right after movement initiation. On several occasions, after perturbing the end
      position of one digit, we found effects also on the kinematics of the opposing
      digit. These findings are in conflict with Smeets and Brenner's double-pointing
      hypothesis.

PMID- 17516059
TI  - The effect of stimulus probability on the somatosensory mismatch field.
AB  - We investigated the effect of deviant stimulus probability on the somatosensory
      magnetic mismatch negativity (MMNm) using an electrical two-point stimulation.
      First, we determined the discrimination threshold (DT) of the two-point distance.
      We applied standard stimuli at a distance that subjects felt as one point and
      deviant stimuli at a distance that subjects definitely felt as two points. We
      used three deviant stimulus probabilities, 10, 30, and 50%. The components
      peaking around 30-70 ms (first component) and 150-250 ms (fourth component)
      following deviant stimuli were significantly larger than those following standard
      stimuli in 10% condition, but not in 30 or 50% condition. The equivalent current
      dipole (ECD) was located in the contralateral primary somatosensory cortex (cSI)
      for the first component, and in the cSI and in the contralateral secondary
      somatosensory cortex (cSII) for the fourth component. The peak amplitude of the
      MMNm decreased as the probability of the deviant stimulus increased. The
      Somatosensory MMNm was affected by deviant stimulus probability similar to an
      auditory mismatch negativity (MMN).

PMID- 17516060
TI  - Ca2+ current of frog vestibular hair cells is modulated by intracellular ATP but
      not by long-lasting depolarisation.
AB  - Some aspects of Ca(2+) channel modulation in hair cells isolated from
      semicircular canals of the frog (Rana esculenta) have been investigated using the
      whole-cell technique and intra and extracellular solutions designed to modify the
      basic properties of the Ca(2+) macrocurrent. With 1 mM ATP in the pipette
      solution, about 60% of the recorded cells displayed a Ca(2+) current constituted
      by a mix of an L and a drug-resistant (R2) component; the remaining 40% exhibited
      an additional drug-resistant fraction (R1), which inactivated in a Ca-dependent
      manner. If the pipette ATP was raised to 10 mM, cells exhibiting the R1 current
      fraction displayed an increase of both the R1 and L components by approximately
      280 and approximately 70%, respectively, while cells initially lacking R1 showed
      a similar increase in the L component with R1 becoming apparent and raising up to
      a mean amplitude of approximately 44 pA. In both cell types the R2 current
      fraction was negligibly affect by ATP. The current run-up was unaffected by
      cyclic nucleotides, and was not triggered by 10 mM ATPgammaS, ADP, AMP or GTP.
      Long-lasting depolarisations (>5 s) produced a progressive, reversible decay in
      the inward current despite the presence of intracellular ATP. Ca(2+) channel
      blockade by Cd(2+) unmasked a slowly activating outward Cs(+) current flowing
      through a non-Ca(2+) channel type, which became progressively unblocked by
      prolonged depolarisation even though Cs(+) and TEA(+) were present on both sides
      of the channel. The outward current waveform could be erroneously ascribed to a
      Ca- and/or voltage dependence of the Ca(2+) macrocurrent.

PMID- 17516061
TI  - Expression of murine killer immunoglobulin-like receptor KIRL1 on CD1d
      independent NK1.1(+) T cells.
AB  - Three mouse killer immunoglobulin-like receptors (KIRs), namely, KIR3DL1, KIRL1,
      and KIRL2, have recently been identified in C56BL/6 (B6) mice. However, only two
      Kir genes are found in the B6 mouse genome sequence data base. To clarify this
      discrepancy, we cloned Kir cDNAs from multiple strains of mice. Sequencing of the
      cDNA clones showed that the Kir3dl1 gene is found in C3H/HeJ and CBA/J but not in
      B6 mice. Analysis of the single nucleotide polymorphism data base suggested that
      Kir3dl1 is the C3H/HeJ and CBA/J allele of Kirl1. We generated mAb to the
      recombinant KIRL1 protein to investigate its expression pattern. The anti-KIRL1
      mAb bound to NK1.1(+) T cells but only very weakly or at undetectable levels to
      other lymphocytes including natural killer (NK) cells and conventional T cells.
      Among NK1.1(+) T cells, conventional NK T cells stained with CD1d tetramer did
      not significantly bind anti-KIRL1 mAb, whereas CD1d-tetramer-negative subset was
      KIRL1-positive. Furthermore, the expression of KIRL1 is readily detected on
      NK1.1(+) T cells from beta(2)-microglobulin-deficient B6 mice. Thus, KIRL1 is
      predominantly expressed on CD1d-independent NK1.1(+) T cells.

PMID- 17516062
TI  - In vivo transport of the intermediates of the penicillin biosynthetic pathway in
      tailored strains of Penicillium chrysogenum.
AB  - Penicillium chrysogenum npe10 (Deltapen; lacking the 56.8-kbp amplified region
      containing the penicillin gene cluster), complemented with one, two, or three
      penicillin biosynthetic genes, was used for in vivo studies on transport of
      benzylpenicillin intermediates. 6-Aminopenicillanic acid (6-APA) was taken up
      efficiently by P. chrysogenum npe10 unlike exogenous delta(L: -alpha-aminoadipyl)
      L: -cysteinyl-D: -valine or isopenicillin N (IPN), which were not taken up or
      were taken up very poorly. Internalization of exogenous IPN and 6-APA inside
      peroxisomes was tested by quantifying their peroximal conversion into
      benzylpenicillin in strains containing only the penDE gene. Exogenous 6-APA was
      transformed efficiently into benzylpenicillin, whereas IPN was converted very
      poorly into benzylpenicillin due to its weak uptake. IPN was secreted to the
      culture medium. IPN secretion decreased when increasing levels of phenylacetic
      acid were added to the culture medium. The P. chrysogenum membrane permeability
      to exogenous benzylpenicillin was tested in the npe10 strain. Penicillin is
      absorbed by the cells by an unknown mechanism, but its intracellular
      concentration is kept low.

PMID- 17516063
TI  - Characterization of alcohol dehydrogenase 1 and 3 from Neurospora crassa
      FGSC2489.
AB  - Alcohol dehydrogenase (ADH) is a key enzyme in the production and utilization of
      alcohols. Some also catalyze the formation of carboxylate esters from alcohols
      and aldehydes. The ADH1 and ADH3 genes of Neurospora crassa FGSC2489 were cloned
      and expressed in recombinant Escherichia coli to investigate their alcohol
      dehydrogenation and carboxylate ester formation abilities. Homology analysis and
      sequence alignment of amino acid sequence indicated that ADH1 and ADH3 of N.
      crassa contained a zinc-binding consensus sequence and a NAD(+)-binding motif and
      showed 54-75% identity with fungi ADHs. N. crassa ADH1 was expressed in E. coli
      to give a specific activity of 289 +/- 9 mU/mg using ethanol and NAD(+) as
      substrate and cofactor, respectively. Corresponding experiments on the expression
      and activity of ADH3 gave 4 mU/mg of specific activity. N. crassa ADH1 preferred
      primary alcohols containing C3-C8 carbons to secondary alcohols such as 2
      propanol and 2-butanol. N. crassa ADH1 possessed 5.3 mU/mg of specific
      carboxylate ester-forming activity accumulating 0.4 mM of ethyl acetate in 18 h.
      Substrate specificity of various linear alcohols and aldehydes indicated that
      short chain-length alcohols and aldehydes were good substrates for carboxylate
      ester production. N. crassa ADH1 was a primary alcohol dehydrogenase using
      cofactor NAD(+) preferably and possessed carboxylate ester-forming activity with
      short chain alcohols and aldehydes.

PMID- 17516064
TI  - Biocatalytic ketone reduction--a powerful tool for the production of chiral
      alcohols--part I: processes with isolated enzymes.
AB  - Enzymes are able to perform reactions under mild conditions, e.g., pH and
      temperature, with remarkable chemo-, regio-, and stereoselectivity. Because of
      this feature, the number of biocatalysts used in organic synthesis has rapidly
      increased during the last decades, especially for the production of chiral
      compounds. The present review highlights biotechnological processes for the
      production of chiral alcohols by reducing prochiral ketones. These reactions can
      be catalyzed by either isolated enzymes or whole cells that exhibit ketone
      reducing activity. The use of isolated enzymes is often preferred because of a
      higher volumetric productivity and the absence of side reactions. Both types of
      catalysts have also deficiencies limiting their use in synthesis of chiral
      alcohols. Because reductase-catalyzed reactions are dependent on cofactors, one
      major task in process development is to provide an effective method for
      regeneration of the consumed cofactors. In this paper, strategies for cofactor
      regeneration in biocatalytic ketone reduction are reviewed. Furthermore,
      different processes carried out on laboratory and industrial scales using
      isolated enzymes are presented. Attention is turned to process parameters, e.g.,
      conversion, yield, enantiomeric excess, and process strategies, e.g., the
      application of biphasic systems or methods of in situ (co)product recovery. The
      biocatalytic production of chiral alcohols utilizing whole cells is presented in
      part II of this review.

PMID- 17516065
TI  - Novel presentation of Kikuchi-Fujimoto disease with chronic, febrile diarrhoea,
      mimicking inflammatory bowel disease.

PMID- 17516066
TI  - A novel mutation of -73(A-->T) in the CCAAT box of the beta-globin gene
      identified in a patient with the mild beta-thalassemia intermedia.
AB  - The beta-thalassemia is one of the most common autosomal recessive disorders in
      Southern China. The point mutation of beta-globin gene is the commonest molecular
      pathogenic mechanism. In Chinese population, over 30 mutations have now been
      identified. In this paper, we describe a novel beta(++)-thalassemia mutation of 
      73(A-->T) within the conserved CCAAT box at position -76 to -72 from the cap site
      of the beta-globin gene. The proband, an 8-year-old Chinese boy, was a compound
      heterozygote of this promoter mutation and a common beta(0)-thalassemia mutation
      of codon 41/42(-TCTT). He had a mild thalassemia intermedia phenotype and was
      transfusion independent with a hemoglobin (Hb) level of 9.4 g/dl, mean
      corpuscular volume (MCV) of 55.2 fl, and mean corpuscular hemoglobin (MCH) of
      17.5 pg. His mother and two maternal uncles were carriers of -73(A-->T) mutation
      in beta-globin gene with hematological phenotype of silent beta-thalassemia. Real
      time quantitative reverse transcript polymerase chain reaction (RT-PCR) analysis
      showed a slightly reduced beta-globin messenger RNA (mRNA) level (19.35%) in
      three heterozygotes compared with that in normal subjects. In restriction
      fragment length polymorphism (RFLP) haplotype analysis, the results indicated
      that this promoter mutation might be linked to the absence of BamHI-3'beta
      restriction site.

PMID- 17516067
TI  - Extramedullary hemopoiesis with littoral cell angioma involving main and
      accessory spleens.

PMID- 17516068
TI  - A phase II study of trastuzumab and capecitabine for patients with HER2
      overexpressing metastatic breast cancer: Japan Breast Cancer Research Network
      (JBCRN) 00 Trial.
AB  - PURPOSE: To determine the response rate and toxicity profile of trastuzumab and
      capecitabine in women with HER2-overexpressing advanced breast cancer. PATIENTS
      AND METHODS: A total of 59 patients from 6 participating centers in Japan entered
      onto the study of trastuzumab and capecitabine. Eighty six percent of women had
      received prior chemotherapy as part of adjuvant (21.4%) or metastatic treatment
      (48.2%), or both (16.1%), including substantial portions of patients who had
      previously received either CMF (7.1%), anthracyclines (28.6%), taxanes (25.0%),
      or both types (25.0%) of chemotherapy. RESULTS: Responses were observed in 28 of
      56 patients (overall response rate, 50%). The response rate was 65.0% in patients
      treated with trastuzumab and capecitabine as first-line therapy for metastatic
      disease, and 62.5% among HER2 +3 positive patients, while high response rates
      were also seen in women treated with second- or third-line therapy. Patients
      receiving trastuzumab and capecitabine as first-line therapy had a longer TTP
      than did patients receiving this treatment as second- or third-line therapy
      (median TTP, 280 vs. 130 days, P < 0.05). Further, patients receiving trastuzumab
      and capecitabine as first-line therapy had longer OS than did patients receiving
      this treatment as second- or third-line therapy (median OS, 780 days vs. 480
      weeks, P < 0.05). The treatment-related adverse events were hand-foot syndrome
      (30.4%), nausea (25%), diarrhea (10.7%), stomatitis (10.7%), fatigue (7.1%), and
      vomiting (5.4%). However, the majority were Grade 1-2 adverse events and only six
      patients experienced Grade 3 adverse events. Further Grade 1 cardiac toxicity was
      observed in one patient, while there were no cases of alopecia and treatment
      related death. CONCLUSION: Trastuzumab in combination with capecitabine is highly
      active in women with HER2-overexpressing metastatic breast cancer and is well
      tolerated.

PMID- 17516069
TI  - A phase II study of milataxel: a novel taxane analogue in previously treated
      patients with advanced colorectal cancer.
AB  - BACKGROUND: Milataxel is a novel taxane analog, with evidence of enhanced
      preclinical activity compared to paclitaxel and docetaxel, especially in cell
      lines that over express P-glycoprotein. Based on preclinical data that milataxel
      may be active in colorectal cancer (CRC), a phase II study was performed in
      patients with advanced previously treated CRC. PATIENTS AND RESULTS: Forty-four
      eligible patients were entered. Milataxel was administered intravenously every 3
      weeks at the dose of 35 mg/m(2). No objective responses were noted, stable
      disease was seen in three patients. The median time to progression was 1.4 months
      (95% CI of 1.2-2.4 months). Three subjects developed neutropenic sepsis and two
      died. The most frequent grade 3/4 adverse events were neutropenia (57%),
      leukopenia (27%), dehydration (14%), neuropathy (16%), diarrhea (14%) and
      thrombocytopenia (14%). The pharmacokinetics of milataxel was assessed in five
      subjects. The mean milataxel elimination half-life was 64 h and the mean area
      under the plasma concentration-time curve was 1,708 ng h/ml. CONCLUSIONS: A
      syndrome of neutropenic sepsis and diarrhea can be life threatening and close
      surveillance is needed in patients treated with milataxel at the dose of 35
      mg/m(2) every 3 weeks. Clinical activity was not demonstrated in patients with
      advanced previously treated CRC.

PMID- 17516070
TI  - Modeling stochastic gene expression under repression.
AB  - Intrinsic transcriptional noise induced by operator fluctuations is investigated
      with a simple spin-like stochastic model. The effects of transcriptional
      fluctuations in protein synthesis are probed by coupling transcription and
      translation by an amplificative interaction. In the presence of repression a new
      term contributes to the noise, which depends on the rate of mRNA production. If
      the switch decay time is small compared with the mRNA life time, the noise is
      also small. In general the damping of protein production by a repressive agent
      occurs linearly but fluctuations can show a maximum at intermediate repression.
      The discrepancy among the switch decay time, the mRNA degradation, and protein
      degradation is crucial for the repressive control in translation without large
      fluctuations. The noise profiles obtained here are in quantitative agreement with
      recent experiments.

PMID- 17516071
TI  - Agrobacterium-mediated transformation of a low glutelin mutant of 'Koshihikari'
      rice variety using the mutated-acetolactate synthase gene derived from rice
      genome as a selectable marker.
AB  - We have developed an efficient rice transformation system that uses only rice
      genome-derived components. The transgenic 'Koshihikari' rice, low-glutelin mutant
      a123, is capable of accumulating large amounts of bioactive peptides in the
      endosperm. Agrobacterium-mediated transformation using the mutated-acetolactate
      synthase (mALS) gene expressed under the control of the callus-specific promoter
      (CSP) as a selectable marker was used to introduce GFP and an anti-hypertensive
      hexapeptide into 'Koshihikari' a123. The CSP:mALS gene cassette confers
      pyrimidinyl carboxy herbicide resistance to transgenic rice callus, but is not
      expressed in regenerated plants. Transformation efficiency of transgenic rice
      line a123 was improved from about 10% to about 30% by modifying callus induction,
      callus selection and regeneration media conventionally used for rice tissue
      culture.

PMID- 17516072
TI  - Isolation of the maize Zpu1 gene promoter and its functional analysis in
      transgenic tobacco plants.
AB  - By screening a genomic library of maize, a 2.2 kb 5' flanking fragment of Zpu1
      gene, encoding the pullulanase-type starch debranching enzyme, was isolated.
      Promoter fragments of various lengths, including the full 5' flanking sequence (
      2267 to -1) (Z1), a 3' deletion (-2267 to -513) (Z5) and three 5' deletions
      extending to -1943 (Z2), -1143 (Z3) and -516 (Z4) upstream of the translational
      initiation codon (ATG), were fused to the GUS reporter gene and introduced into
      tobacco. When these constructs were tested in transgenic tobacco plants, seed
      preferred GUS activity was observed in pZ1-transgenic lines. In pZ2-transgenic
      lines, the GUS activity was not only restricted to seeds, but was also detected
      in calyxes, petals, stamens and mature leaves. At the same time, negligible GUS
      activity was detected in roots, stems, young leaves, stigmas and ovaries from the
      transgenic tobacco plants, which had integrated the full isolated sequence of
      Zpu1 promoter or its deletions. Deletion analysis indicated that the promoter
      contained a putative positive cis-regulatory element and the proximal region (
      516 to -1) was essential for directing the expression of gus reporter gene.
      Analysis of GUS activity during the fruit development and seed germination
      suggested that Zpu1 promoter is active both in starch anabolism and in starch
      catabolism, which is consistent with the function of the endogenous gene in
      maize. GUS activity in leaves under light and darkness confirmed that Zpu1
      promoter functions in the starch degradation of photosynthetic tissues in the
      dark phase of the diurnal cycle.

PMID- 17516073
TI  - High efficiency Agrobacterium rhizogenes-mediated transformation of Saponaria
      vaccaria L. (Caryophyllaceae) using fluorescence selection.
AB  - A highly efficient and convenient method for the Agrobacterium rhizogenes
      dependent production of transformed roots of Saponaria vaccaria L.
      (Caryophyllaceae) is described. The parameters tested and optimized include S.
      vaccaria cultivar, explant type, Agrobacterium rhizogenes strain and culture
      conditions. For cotransformation using additional recombinant T-DNA-containing A.
      rhizogenes strains, use of neomycin phosphotransferase and enhanced green
      fluorescent protein genes as selectable markers were tested alone and in
      combination. Optimal results, yielding a minimum of one transformed root per
      explant, were obtained using the cultivar Pink Beauty, the A. rhizogenes strain
      LBA9402 and internode explants precultured on a phytohormone mixture. Selection
      of cotransformed roots by observation of enhanced green fluorescent protein
      fluorescence alone was highly effective and convenient.

PMID- 17516074
TI  - Regulation of FAT/CD36 mRNA gene expression by long chain fatty acids in the
      differentiated 3T3-L1 cells.
AB  - Defects in fatty acid translocase (FAT/CD36) have been identified as a major
      factor in insulin resistance and defective fatty acid and glucose metabolism.
      Therefore, understanding of the regulation of FAT/CD36 expression and function is
      important for a potential therapeutic target for type II diabetes. We
      differentiated 3T3-L1 preadipocytes into matured adipocytes and examined the
      roles of insulin and long chain fatty acids on FAT/CD36 expression and function.
      Our results indicate that FAT/CD36 mRNA expression was not detected at
      preadipocyte but was significantly increased at matured adipocyte. In fully
      differentiated 3T3-L1 adipocytes, insulin significantly increased FAT/CD36 mRNA
      and protein expression in a dose dependent manner. The free fatty acid stearic
      acid reduced FAT/CD36 mRNA expression while the non-metabolizable free fatty acid
      alpha-bromopalmitate (2-BP) significantly increased FAT/CD36 mRNA and protein
      expression. Isoproterenol, in contrast, dose-dependently reduced FAT/CD36 mRNA
      expression and increased free fatty acid release. Mechanism analysis indicated
      that the effect of insulin and 2-BP on the FAT/CD36 mRNA gene expression may be
      mediated through activation of PPAR-gamma, suggesting that FAT/CD36 may have
      important implications in the pathophysiology of defective fatty acid metabolism.

PMID- 17516075
TI  - Long-term results of delayed primary anastomosis for pure oesophageal atresia: a
      27-year follow up.
AB  - The management of a newborn with pure oesophageal atresia continues to be
      challenging. We started treating babies with pure oesophageal atresia by delayed
      primary anastomosis in 1977. The purpose of this study was to review the long
      term outcome in infants with pure oesophageal atresia (EA) treated by delayed
      primary anastomosis with special emphasis on gastroesophageal reflux (GOR)
      related morbidity. The medical charts of all patients treated by delayed primary
      anastomosis between 1977 and 2004 were retrospectively reviewed. All survivors
      were followed up with completion of a questionnaire and personal/phone
      interviews. There were 26 patients in total admitted during the 27-year study
      period with the diagnosis of pure oesophageal atresia. Three died prior to
      surgery due to associated anomalies; two had almost no distal oesophageal segment
      and underwent oesophageal replacement surgery. The remaining 21 children were
      treated with delayed primary anastomosis and made up our study group. There were
      four deaths (19%) in this group, and all were prior to 1980. The median
      gestational age was 35.5 weeks and the median birth weight was 2.6 kg; median
      initial gap was 3.7 cm and median preoperative gap was 1.5 cm; median age at
      operation was 80 days and the median hospital stay was 5.5 months. The median
      follow-up period was 13.5 years. Fourteen children (66%) developed symptomatic
      gastroesophageal reflux and nine of these needed fundoplication (43%). Sixteen
      children developed strictures at the anastomotic site; ten responded to repeated
      dilatations while six needed resection and reanastomosis. At the time of this
      study, 15 out of the 17 survivors (88%) were on normal diet with no respiratory
      problems and 2 (12%) were dependent on gastrostomy feeds. Our long-term follow-up
      data shows that the delayed primary anastomosis provides excellent functional
      results in patients born with pure oesophageal atresia. The high incidence of
      gastroesophageal reflux and associated morbidity requires early intervention to
      prevent ongoing feeding problems due to oesophagitis and stricture formation.

PMID- 17516076
TI  - [B lymphocyte differentiation in granulomatous tissues of the lung and the nasal
      mucosa in Wegener's granulomatosis: origin of anti-neutrophil cytoplasmic
      antibody formation?].
AB  - Wegener's granulomatosis (WG) starts with granulomatous inflammation of the
      respiratory tract before it converts into a potentially organ and life
      threatening systemic vasculitis associated with anti-neutrophil cytoplasmic
      antibodies (ANCA). The site of formation of the highly specific ANCA directed
      against "Wegener's autoantigen" proteinase 3 (PR3) is still unknown. Previously,
      we have shown that follicle-like B lymphocytic infiltrates in the vicinity to PR3
      expressing cells in WG-granulomata. We characterized the immunoglobulin-VH
      repertoire in lung and nasal granulomata (paraffin embedded) from four WG
      patients. A total of 115 individual VH genes were characterized and compared to
      84 VH genes from the peripheral blood of a healthy donor. We found an increased
      frequency of mutations with a bias to amino acid exchanges within the antigen
      binding sites (CDR) 1 and 2 in WG tissue. A large number of mutations led to
      negatively charged amino acids and may increase affinity to the positively
      charged PR3. Furthermore, the occurrence of differently mutated members of one B
      cell clone indicates clonal expansion and intraclonal diversification by an
      antigen, e.g. PR3. Several WG tissue derived genes displayed similarities to
      published sequences from peripheral PR3 ANCA producing B cells. Thus, granulomata
      of the lower and upper respiratory tract contain follicle-like B cell clusters
      with a selected VH repertoire infiltrate in WG. WG granulomata could be the place
      of autoantigen presentation and formation of high-affinity ANCA within neoformed
      ectopic or tertiary lymphoid-like tissue areas.

PMID- 17516077
TI  - Bacteriology of acute rhinosinusitis in nasopharyngeal carcinoma survivors: a
      result of maxillary sinus punctures.
AB  - Rhinosinusitis is a common complication in patients with nasopharyngeal carcinoma
      (NPC) who receive radiotherapy. An impaired mucociliary clearance due to this
      treatment may be the major cause of rhinosinusitis in these irradiated patients.
      The relative frequency with which various pathogens cause rhinosinusitis in these
      patients is unknown. This study investigates the bacteriology of acute
      rhinosinusitis in irradiated NPC patients by maxillary sinus puncture. From
      October 2001 through July 2006, 20 irradiated NPC patients with radiograph-proven
      acute maxillary sinusitis received maxillary sinus punctures. Aspirate contents
      of the sinuses were collected for aerobic and anaerobic cultivation. A total
      sampling of 26 sides was performed in the 20 patients. The culture rate was 85%.
      Frequently identified aerobes and facultative anaerobes included alpha-hemolytic
      streptococcus (n = 8), Staphylococcus aureus (n = 5) and Pseudomonas aeruginosa
      (n = 3). Streptococcus pneumoniae, Haemophilus influenzae and Moraxella
      catarrhalis, however, are far less common. This may provide important information
      about the antibiotic therapy in irradiated NPC patients with acute
      rhinosinusitis.

PMID- 17516078
TI  - Uncinectomy: Stammberger or swing-door technique?
AB  - Uncinectomy is the first step performed in functional endoscopic sinus surgery
      (FESS). The technique of performing uncinectomy by various methods depends on
      training and personal preferences. A postal survey of 585 practising British
      otorhinolaryngologists has revealed no significant difference in the various
      techniques of uncinectomies described by Stammberger and the swing-door technique
      (Wormald). Most surgeons are comfortable with the various techniques of
      uncinectomy, although the Stammberger technique (45.20%) appears to be easier
      compared to swing-door (37.34%). The postoperative complications including any
      comments have been recorded. The aim of this study was to determine which
      technique of uncinectomy (Stammberger, swing-door) was well advocated by the UK
      otorhinolaryngologists in FESS.

PMID- 17516079
TI  - Differences in regulation of carbohydrate metabolism during early fruit
      development between domesticated tomato and two wild relatives.
AB  - Early development and growth of fruit in the domesticated tomato Solanum
      lycopersicum cultivar Money Maker and two of its wild relatives, S. peruvianum
      LA0385 and S. habrochaites LA1777, were studied. Although small differences
      exist, the processes involved and the sequence of events in fruit development are
      similar in all three species. The growth of developing fruits is exponential and
      the relative growth rate accelerates from 5 days after pollination (DAP 5) to DAP
      8, followed by a decline during further development. Growth is positively
      correlated to the standard "Brix plus starch'' in the period DAP 8-DAP 20.
      Carbohydrate composition and levels of sugars and organic acids differ in fruits
      of the wild accessions compared to domesticated tomato. The wild accessions
      accumulate sucrose instead of glucose and fructose, and ripe fruits contain
      higher levels of malate and citrate. The enzymes responsible for the accumulation
      of glucose and fructose in domesticated tomatoes are soluble invertase and
      sucrose synthase. The regulation of initial carbohydrate metabolism in the
      domesticated tomato differs from that in the wild species, as could be concluded
      from measuring activities of enzymes involved in primary carbohydrate metabolism.
      Furthermore, changes in the activity of several enzymes, e.g., cell wall
      invertase, soluble invertase, fructokinase and phosphoglucomutase, could be
      attributed to changes in gene expression level. For other enzymes, additional
      control mechanisms play a role in the developing tomato fruits. Localization by
      in-situ activity staining of enzymes showed comparable results for fruits of
      domesticated tomato and the wild accessions. However, in the pericarp of S.
      peruvianum, less activity staining of phosphogluco-isomerase, phosphoglucomutase
      and UDP-glucosepyrophosphorylase was observed.

PMID- 17516080
TI  - Iron deficiency-mediated stress regulation of four subgroup Ib BHLH genes in
      Arabidopsis thaliana.
AB  - Networks of transcription factors control physiological, developmental and
      environmental responses. Root iron acquisition responses are controlled by the
      essential bHLH protein FIT. Recently, two group Ib BHLH genes were reported to be
      iron deficiency-regulated. Here, we studied expression patterns of these two
      group Ib BHLH genes and of their two closest homologs to analyze whether their
      regulation would support a function in iron deficiency responses. We found that
      BHLH038, BHLH039, BHLH100 and BHLH101 (comprising a subgroup of BHLH Ib genes)
      were up regulated by iron deficiency in roots and leaves. Single insertion
      mutants had no visible phenotype and were capable of inducing root iron
      acquisition responses, presumably due to functional redundancy. Specific metal
      treatments like nickel, high zinc or high copper resulted in induction of the
      four BHLH Ib genes whereas high iron, low copper and low zinc repressed gene
      expression. Induction of the four BHLH Ib genes was also found in multiple iron
      acquisition mutants including fit. Ectopic activation of FIT did not suppress the
      four BHLH Ib genes. Split-root analyses using promoter-GUS lines showed that FIT
      and BHLH100 promoters were controlled by different local and systemic signals
      involved in their regulation by iron. These results indicated that the four BHLH
      Ib genes were induced independently from FIT by conditions causing iron
      deficiency. Taken together, BHLH038, BHLH039, BHLH100 and BHLH101 function
      differently from FIT and may be involved in mediating a signal related to iron
      deficiency-induced stress and/or internal iron homeostasis.

PMID- 17516081
TI  - Segmental expression of Pax3/7 and engrailed homologs in tardigrade development.
AB  - How morphological diversity arises through evolution of gene sequence is a major
      question in biology. In Drosophila, the genetic basis for body patterning and
      morphological segmentation has been studied intensively. It is clear that some of
      the genes in the Drosophila segmentation program are functioning similarly in
      certain other taxa, although many questions remain about when these gene
      functions arose and which taxa use these genes similarly to establish diverse
      body plans. Tardigrades are an outgroup to arthropods in the Ecdysozoa and, as
      such, can provide insight into how gene functions have evolved among the
      arthropods and their close relatives. We developed immunostaining methods for
      tardigrade embryos, and we used cross-reactive antibodies to investigate the
      expression of homologs of the pair-rule gene paired (Pax3/7) and the segment
      polarity gene engrailed in the tardigrade Hypsibius dujardini. We find that in H.
      dujardini embryos, Pax3/7 protein localizes not in a pair-rule pattern but in a
      segmentally iterated pattern, after the segments are established, in regions of
      the embryo where neurons later arise. Engrailed protein localizes in the
      posterior ectoderm of each segment before ectodermal segmentation is apparent.
      Together with previous results from others, our data support the conclusions that
      the pair-rule function of Pax3/7 is specific to the arthropods, that some of the
      ancient functions of Pax3/7 and Engrailed in ancestral bilaterians may have been
      in neurogenesis, and that Engrailed may have a function in establishing
      morphological boundaries between segments that is conserved at least among the
      Panarthropoda.

PMID- 17516082
TI  - False negative 17-hydroxyprogesterone screening in children with classical
      congenital adrenal hyperplasia.
AB  - We report 5 out of 214 children with classical congenital adrenal hyperplasia
      (CAH) that was not detected by neonatal 17-Hydroxyprogesterone screening.
      Therefore, diagnosis was only based on a suspect clinical picture and subsequent
      re-evaluation. In addition to 3 patients suffering from the simple virilizing
      form of CAH and not reported so far, the remaining 2 children whose CAH was
      missed by the screening suffered from the severe salt-wasting form. This report
      underlines the importance of a careful clinical investigation of newborns to
      detect signs of genital virilization. The differential diagnosis of classical CAH
      should be kept in mind even if neonatal screening is reported to be normal.

PMID- 17516083
TI  - Rare association of Hirschsprung's disease and Joubert syndrome.
AB  - We present the case of an 18-month-old boy with Hirschsprung's disease who had
      psychomotor retardation. His clinical and radiological findings were consistent
      with Joubert syndrome. The patient was the second case to show the association
      between Hirschsprung's disease and Joubert syndrome in the literature. As in our
      case, association of these entities by chance seems to be unlikely. Genetic
      analysis of new Joubert syndrome and Hirschsprung's disease patients may identify
      the candidate genes.

PMID- 17516085
TI  - Immunoprophylaxis failure against vertical transmission of hepatitis B virus:
      what is the mechanism and do other factors also play a role?

PMID- 17516084
TI  - What's new in surfactant? A clinical view on recent developments in neonatology
      and paediatrics.
AB  - Surfactant therapy has significantly changed clinical practice in neonatology
      over the last 25 years. Recent trials in infants with respiratory distress
      syndrome (RDS) have not shown superiority of any natural surfactant over another.
      Advancements in the development of synthetic surfactants are promising, yet to
      date none has been shown to be superior to natural preparations. Ideally,
      surfactant would be administered without requiring mechanical ventilation. An
      increasing number of studies investigate the roles of alternative modes of
      administration and the use of nasal continuous positive airway pressure to
      minimise the need for mechanical ventilation. Whether children with other lung
      diseases benefit from surfactant therapy is less clear. Evidence suggests that
      infants with meconium aspiration syndrome and children with acute lung
      injury/acute respiratory distress syndrome may benefit, while no positive effect
      of surfactant is seen in infants with congenital diaphragmatic hernia. However,
      more research is needed to establish potential beneficial effects of surfactant
      administration in children with lung diseases other than RDS. Furthermore,
      genetic disorders of surfactant metabolism have recently been linked to
      respiratory diseases of formerly unknown origin. It is important to consider
      these disorders in the differential diagnosis of unexplained respiratory distress
      although no established treatment is yet available besides lung transplantation
      for the most severe cases. CONCLUSION: Research around surfactant is evolving and
      recent developments include further evolution of synthetic surfactants,
      evaluation of surfactant as a therapeutic option in lung diseases other than RDS
      and the discovery of genetic disorders of surfactant metabolism. Ongoing research
      is essential to continue to improve therapeutic prospects for children with
      serious respiratory disease involving disturbances in surfactant.

PMID- 17516086
TI  - Mechanographic characteristics of adolescents and young adults with congenital
      heart disease.
AB  - The present study comprised 29 adolescents and young adults (15 females, 14
      males; aged 14.1-23.9 years) with congenital heart disease (CHD) and focused on
      the interaction between the biomechanical system and CHD. Individuals were
      characterized by auxological (height, weight), dynamometric (MIGF, maximal
      isometric grip force) and mechanograpic parameters (Vmax, maximal velocity; PJF,
      peak jump force; PJP, peak jump power; time of five stand-ups in chair-rising
      test). PJF, PJP and MIGF were transformed into height-related SD-scores. MIGF-SDS
      and PJP-SDS were lower in the CHD patients than in reference individuals. PJP-SDS
      was lower than PJF-SDS. PJP-SDS was correlated to Vmax (r = 0.62) and to the time
      of five-stand-ups in chair-rising (r = -0.62). Transcutaneous oxygen saturation
      and NYHA classes were correlated to Vmax (r = 0.42 and r = -0.57, respectively)
      and to chair-rising performance (r = -0.60 and r = 0.50, respectively). To
      conclude, individuals with CHD are characterized by an impaired inter- and
      intramuscular coordination, which is characterized by a greater decrease in
      muscular power than muscle force.

PMID- 17516087
TI  - Accuracy of clinical criteria for the diagnosis of hepatocellular carcinoma
      without biopsy in a Hepatitis B virus-endemic area.
AB  - OBJECTIVES: Several sets of criteria have been suggested for clinical diagnosis
      of hepatocellular carcinoma (HCC) without biopsy but there are no comprehensive
      data to support the usefulness of these criteria. Here, we sought to validate the
      accuracy of our clinical criteria for HCC diagnosis in a cohort of patients, and
      further tested the effect of HBV and clinical cirrhosis status on diagnostic
      accuracy. METHODS: A total of 232 patients with liver nodules >1 cm in diameter
      who underwent surgical resection or liver biopsy, and had fulfilled all required
      examinations for clinical non-invasive diagnosis of HCC were reviewed
      retrospectively. RESULTS: Hepatitis B virus (HBV) was positive in 170 patients
      (73.3%). One hundred and eighty-nine cases were diagnosed as HCC using the
      clinical criteria and 186 cases of HCC were confirmed by pathologic examination.
      The overall sensitivity, specificity and positive predictive value of the
      clinical criteria were 95.1, 73.9 and 93.7%, respectively. The accuracy was not
      significantly affected by lesion size (1-2 cm vs. >2 cm) or the presence of
      clinical cirrhosis. The sensitivities were 97.3 and 86.8% in the HBsAg positive
      group and non-HBV group, respectively (P<0.001), and the specificities were 56.5
      and 91.3%, respectively (P<0.001). CONCLUSIONS: The clinical criteria for the
      diagnosis of HCC showed an acceptable accuracy irrespective of lesion size or the
      presence of clinical cirrhosis in an HBV-endemic population. However, the
      presence of HBV affected the sensitivity and specificity of the clinical criteria
      for HCC diagnosis in an HBV endemic area.

PMID- 17516088
TI  - Prediction of chronic hepatitis B, liver cirrhosis and hepatocellular carcinoma
      by SELDI-based serum decision tree classification.
AB  - PURPOSE: To screen potential serological biomarkers and develop decision tree
      classifications of chronic hepatitis B, liver cirrhosis (LC) and hepatocellular
      carcinoma (HCC), respectively, with high prediction score for improving diagnosis
      of liver diseases. METHODS: The total serum samples were randomly divided into
      three training sets (41 HBV and 35 health; 36 LC and 35 health; 39 HCC and 35
      health) and three testing groups (34 HBV and 38 health; 18 LC and 52 health; 42
      HCC and 47 health). Selected WCX2 protein chip capture followed by SELDI-TOF-MS
      analysis was applied to generate the serum protein profiles. Subsequently serum
      protein spectra were normalized and aligned by Ciphergen SELDI Software 3.1.1
      with Biomarker Wizard including baseline subtraction, mass accuracy calibration,
      automatic peak detection. Once the intensities of selected significant peaks from
      the training data set were transferred to further BPS analysis, an optimized
      classification tree with sequence-decision was established to divide training
      data set into disease group and control group successfully. A double blind test
      was employed to determine the clinical sensitivity and clinical specificity of
      three models. RESULTS: After comparative analysis of SELDI based serum protein
      profile between the cases of disease and healthy, a HCC decision tree
      classification with sensitivity of 94.872% and specificity of 94.286%; a LC
      decision tree classification with sensitivity of 91.667% and specificity of
      94.286% and a HBV decision tree classification with sensitivity of 95.122% and
      specificity of 94.286% were produced by BPS respectively. When three decision
      tree models were challenged by the double-blind test samples, clinical
      sensitivity and clinical specificity of these models were predicted in diagnosis
      of three liver diseases (HCC: 90.48 and 89.36%; cirrhosis: 100 and 86.5%; HBV:
      85.29 and 84.21%). CONCLUSION: SELDI-based decision tree classifications showed
      great advantages over conventional serological biomarkers in the diagnosis of
      chronic hepatitis B, LC as well as HCC.

PMID- 17516089
TI  - Ursolic acid, a naturally occurring triterpenoid, demonstrates anticancer
      activity on human prostate cancer cells.
AB  - PURPOSE: Glucocorticoids are widely used as adjuvant therapy in hormonal
      refractory prostate cancer; their therapeutic role, however, remains unclear.
      Ursolic acid, a natural triterpene, structurally similar to dexamethasone,
      exhibits antitumor effects in various cell types. Our main objective was to
      investigate the effects of ursolic acid on cell viability, apoptosis and bcl-2
      protein, in human hormone refractory and androgen-sensitive prostate cancer
      cells. METHODS: The ursolic acid-induced changes in cell viability, apoptosis and
      bcl-2 protein were examined in human hormone refractory prostate cancer PC-3
      cells and androgen-sensitive LNCaP cells, by MTT assay, flow cytometry and
      western blot analysis, respectively. RESULTS: Ursolic acid inhibited
      significantly the cell viability and induced apoptosis in PC-3 cells at 55 microM
      and in LNCaP cells at 45 microM associated with a downregulation of bcl-2
      protein. CONCLUSIONS: The antiproliferative and apoptotic effects of ursolic acid
      in PC-3 and LNCaP cells implicate its potential therapeutic use for the treatment
      of hormone refractory and androgen-sensitive prostate cancer. The downregulation
      of bcl-2 may be one of the molecular mechanisms via which it induces apoptosis in
      PC-3 and LNCaP cells.

PMID- 17516090
TI  - Dynamics of dissolved oxygen isotopic ratios: a transient model to quantify
      primary production, community respiration, and air-water exchange in aquatic
      ecosystems.
AB  - Dissolved O(2) is an important aquatic ecosystem health indicator. Metabolic and
      gas exchange (G) rates, which control O(2) concentration, are affected by
      nutrient loading and other environmental factors. Traditionally, aquatic
      metabolism has been reported as primary production:community respiration (P:R)
      ratios using diel measurements and interpretations of dissolved O(2) and/or CO(2)
      concentrations, and recently using stable isotopes (delta(18)O, Delta(17)O) and
      steady state assumptions. Aquatic ecosystems, such as rivers and ponds, are not
      at steady state and exhibit diel changes, so steady state approaches are often
      inappropriate. A dynamic O(2) stable isotope model (photosynthesis-respiration
      gas exchange; PoRGy) is presented here, requiring a minimum of parameters to
      quantify daily averaged P, R, and G rates under transient field conditions.
      Unlike steady state approaches, PoRGy can address scenarios with 100% O(2)
      saturation but with delta(18)O-O(2) values that are not at air equilibrium. PoRGy
      successfully accounts for isotopic G when applied to an oxygen isotope
      equilibration laboratory experiment. PoRGy model results closely matched the diel
      O(2) and delta(18)O-O(2) data from three field sites with different P:R:G ratios
      and various P, R and G rates. PoRGy provides a new research tool to assess
      ecosystem health and to pose environmental impact-driven questions. Using daily
      averaged rates was successful and thus they can be used to compare ecosystems
      across seasons and landscapes.

PMID- 17516091
TI  - Experimental studies of diaspore attachment to animal coats: predicting
      epizoochorous dispersal potential.
AB  - The transport of diaspores on animal hairs depends on the ability of a diaspore
      to attach to the hair and to be retained in it over longer periods of time.
      Whereas several studies of diaspore retention on animal hairs have been conducted
      recently, the process of diaspore attachment to the hair has not yet been studied
      systematically. We describe a new method to quantify the attachment potential
      (AtP) of plant diaspores. Attachment potential was measured as the proportion of
      diaspores of a given species that attached to pieces of an animal coat in a
      standardised experiment. The experiment was conducted for 58 plant species (herbs
      and grasses) and three different coat types: sheep wool, cattle and roe deer
      hair. Attachment potentials differed widely between the three coat types, but
      also between plant species. We found diaspore surface structure (a quantitative
      measure of diaspore morphology) and diaspore exposition (describing the
      morphology of the infructescence) to be the most important plant traits
      regulating AtP. An influence of seed mass on attachment potential could not be
      detected. For sheep wool, a general linear model (with diaspore exposure as a
      factor and diaspore surface structure as covariate) explained 77% of the
      variation in AtPs. To validate this model, we predicted AtPs for 27 additional
      species and compared these to the measured Atps; the predicted and measured
      AtPscorrelated significantly with r(s) = 0.68. A comparison of attachment and
      retention potentials to sheep wool for 127 randomly selected plant species showed
      that attachment and retention are only very weakly correlated, indicating that
      both processes act rather independently of each other. Since many diaspores seem
      to perform well in only one of these processes, attachment can be considered to
      be as equally as decisive as retention in terms of epizoochorous dispersal.

PMID- 17516092
TI  - Predictors of short and long-term outcome in patients with hematological
      disorders admitted to the intensive care unit for a life-threatening
      complication.
AB  - GOAL OF WORK: The admission of patients with hematological disorders to the
      intensive care unit (ICU) involves a complex resource usage and may be associated
      with high mortality. The decision making to transfer a severely ill patient to
      the ICU, therefore, presents an ethical dilemma. We assessed both early and long
      term outcomes in relation to clinical characteristics with the aim to facilitate
      clinical decision making. MATERIALS AND METHODS: We performed a cohort study of
      hematological patients admitted to ICU at a university hospital. MAIN RESULTS:
      During a 6-year period (1996-2001), 85 patients with a median age of 59 years
      were admitted to ICU. The majority of patients (88%) suffered from hematological
      malignancies. Major reasons for ICU admission were respiratory failure (41%) and
      septic shock/pre-shock (24%). The median duration of ICU admission was 2 (1-67)
      days. Crude in-ICU, 30-day, and 6-month mortality rates were 30, 49, and 62%,
      respectively. Overall 5-year survival rate was 20%, and 13 (15%) patients were
      alive at time of follow-up (median 7.4 years). Respiratory failure requiring
      ventilatory support and a high Acute Physiology and Chronic Health Evaluation II
      score was significantly correlated to high in-ICU mortality, but not to long-term
      outcome. Type of hematological malignancy, neutropenia, thrombocytopenia,
      bacteremia, prior administration of chemotherapy, age, or gender was not
      significantly associated with outcome. CONCLUSIONS: The current study provides
      encouraging results on long-term post-ICU outcome also in elderly patients with
      hematological diseases. For a substantial proportion of critically ill
      hematological patients, a short time care at an ICU is lifesaving. These patients
      should be offered intensive care unless or until it is clear that there is little
      prospect of recovery from the acute illness or that the underlying malignancy
      cannot be controlled.

PMID- 17516093
TI  - A phase I study to assess the safety and activity of topical lovastatin (FP252S)
      for the prevention of chemotherapy-induced alopecia.
AB  - INTRODUCTION: A phase I study was performed to establish the minimum effective
      dose safety of the topical 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase
      inhibitor lovastatin (FP252S) in preventing chemotherapy-induced alopecia in
      cohorts of three patients receiving their first doses of chemotherapy with
      doxorubicin (eight patients) or taxanes (four patients). RESULTS: One patient at
      the first dose level receiving doxorubicin and cyclophosphamide had only grade 1
      hair loss at 3 weeks. At dose level 2, one patient on doxorubicin took more than
      4 weeks to lose her hair and another on docetaxel retained some hair throughout
      her chemotherapy. At level 3, one patient had grade 2 hair loss at week 4 and
      another on docetaxel for 6 cycles showed evidence of hair growth between cycles.
      There were no grade 3 or 4 toxicities, but at the fourth dose level, no higher
      concentrations could be formulated. DISCUSSION: Lovastatin was well-tolerated at
      the maximum concentration achievable but showed little efficacy.

PMID- 17516094
TI  - Psychological distress of female cancer caregivers: effects of type of cancer and
      caregivers' spirituality.
AB  - INTRODUCTION: This study examined the effects of the survivor's cancer type
      (gender-specific vs nongender-specific) and the female caregiver's spirituality
      and caregiving stress on the caregiver's psychological distress. Cancer
      caregivers, who were nominated by cancer survivors, participated in a nationwide
      quality-of-life survey with 252 caregivers providing complete data for the
      variables. PATIENTS AND METHODS: Breast and ovarian cancer were categorized as
      gender-specific types of cancer (GTC+), whereas kidney, lung, non-Hodgkin's
      lymphoma (NHL), and skin melanoma cancers were GTC-. Spirituality, caregiving
      stress, and psychological distress were measured using the functional assessment
      of chronic illness therapy--spiritual well-being, stress overload subscale, and
      profile of mood states--short form, respectively. RESULTS AND DISCUSSION:
      Hierarchical regression analyses revealed that female caregivers whose care
      recipient was diagnosed with a nongender specific type of cancer (GTC- group)
      reported higher psychological distress than did the GTC+ group. The GTC- group
      also reported lower spirituality and higher caregiving stress related to higher
      psychological distress than did the GTC+ group. In addition, the beneficial
      effect of spirituality on reducing psychological distress was more pronounced
      among the GTC- group or when caregiving stress increased. CONCLUSIONS: Our
      findings suggest that female caregivers of survivors with a nongender-specific
      cancer may benefit from programs designed to reduce their psychological distress,
      and caregivers who are low in spirituality need help to derive faith and meaning
      in the context of cancer care.

PMID- 17516095
TI  - Flavonoids induce germination of basidiospores of the ectomycorrhizal fungus
      Suillus bovinus.
AB  - Under laboratory conditions, spores of ectomycorrhizal fungi usually germinate
      very poorly or not at all. In a previous study, we showed that spores of the
      ectomycorrhizal fungus Suillus bovinus germinated through the combination of
      activated charcoal treatment of media and co-culture with seedlings of Pinus
      densiflora, which suggested that some substances contained in root exudates
      induced the germination. Among the compounds reported from root exudates,
      flavonoids have been elucidated to play various and substantial roles in plant
      microbe interactions; we therefore investigated the effects of flavonoids on
      basidiospore germination of S. bovinus by the diffusion gradient assay on water
      agar plates pretreated with charcoal powder. Seven out of the 11 flavonoids
      tested, hesperidin, morin, rutin, quercitrin, naringenin, genistein, and chrysin,
      had greater effects than controls, whereas flavone, biochanin A, luteolin, and
      quercetin showed no positive effects. The effective concentration presumably
      corresponded to several micromolar levels, which was equivalent to those
      effective for pollen development, nod gene induction, and spore germination of F.
      solani f. sp. pisi and AM fungi. The results suggest that flavonoids play a role
      as signaling molecules in symbiotic relationships between woody plants and
      ectomycorrhizal fungi.

PMID- 17516096
TI  - Human serum albumin coordinates Cu(II) at its N-terminal binding site with 1 pM
      affinity.
AB  - The conditional stability constant at pH 7.4 for Cu(II) binding at the N-terminal
      site (NTS) of human serum albumin (HSA) was determined directly by competitive UV
      vis spectroscopy titrations using nitrilotriacetic acid (NTA) as the competitor
      in 100 mM NaCl and 100 mM N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid
      (Hepes). The log Kc (NTS) value of 12.0 +/- 0.1 was determined for HSA dissolved
      in 100 mM NaCl. A false log log Kc (NTS) (c) value of 11.4 +/- 0.1 was obtained
      in the 100 mM Hepes buffer, owing to the formation of a ternary Cu(NTA)(Hepes)
      complex. The impact of the picomolar affinity of HSA for Cu(II) on the
      availability of these ions in neurodegenerative disorders is briefly discussed.

PMID- 17516097
TI  - Identification of (eta6-arene)ruthenium(II) protein binding sites in E. coli
      cells by combined multidimensional liquid chromatography and ESI tandem mass
      spectrometry: specific binding of [(eta6-p-cymene)RuCl2 (DMSO)] to stress
      regulated proteins and to helicases.
AB  - An automated multidimensional protein identification technology, which combines
      biphasic liquid chromatography with electrospray ionisation tandem mass
      spectrometry (MS/MS), was employed to analyse tryptic peptides from Escherichia
      coli cells treated with the antiproliferation agent [(eta(6)-p
      cymene)RuCl(2)(DMSO)], where DMSO is dimethyl sulfoxide. MS/MS spectra were
      recorded for molecular ions generated by neutral loss of p-cymene from intensive
      peptide ions coordinated by the (eta(6)-p-cymene)Ru(II) fragment. Matching of the
      MS/MS spectra of the ruthenated peptides to spectra of proteins in the E. coli
      database enabled the identification of five protein targets for [(eta(6)-p
      cymene)RuCl(2)(DMSO)]. One of these is the constitutive cold-shock protein cspC,
      which regulates the expression of genes encoding stress-response proteins, and
      three of the other targets, ppiD, osmY and sucC, are proteins of the latter type.
      The DNA damage-inducible helicase dinG was likewise established as a protein
      target. Aspartate carboxylate functions were identified as the probable Ru
      binding sites in cspC, ppiD and dinG, and threonine and lysine side chains in
      osmY and sucC, respectively.

PMID- 17516098
TI  - Computational prediction of the regio- and diastereoselectivity in a rhodium
      catalyzed hydroformylation/cyclization domino process.
AB  - The regioselectivity of the hydroformylation reaction of 2-methyl-3-(3
      acetylpyrrol-1-yl)prop-1-ene catalyzed by an unmodified Rh catalyst has been
      investigated at the B3LYP/6-31G* level with Rh described by effective core
      potentials in the LANL2DZ valence basis set. Considering the population of all
      the H-Rh(CO)3-olefin transition state complexes, a regioselectivity ratio (B:L)
      of 12:88 has been obtained, in satisfactory agreement with the experiment
      producing the chiral linear aldehyde as the only product. The aldehyde, after
      complete diastereoselective cyclization, yields a 1:1 mixture of 1-acetyl-6R(S)
      methyl-8R(S)-hydroxy-5,6,7,8-tetrahydroindolizine (having the same configuration
      on both stereogenic carbon atoms) and 2-acetyl-6-methyl-5,6-dihydroindolizine
      [Lett Org Chem (2006) 3:10-12]. The reason for such a high degree of
      diastereoselectivity has been elucidated examining the B3LYP/6-31G* potential
      energy surface for the reactions leading to the RR and RS diastereomers on a
      model system (without the acetyl substituent) and the actual compound. In the
      absence of a catalyst, a very high barrier is found along the reaction pathway,
      whereas spontaneous annulation occurs to a protonated pentahydroindolizine in the
      presence of H+. When a counterion (F-) is added, the proton on the newly formed
      tetrahedral carbon is abstracted, obtaining a structure closer to the final
      product (tetrahydroindolizine). Replacing H+ with Rh+, an initial adduct along
      the RS path much more favorable than any of those computed along the RR one is
      located because of the presence of the acetyl group. Tentative approaching paths
      obtained using [Rh(CO)3]+, bound to the aldehyde O, feature a higher barrier
      along the RS one, and offer a convincing explanation for the observed
      diastereoselectivity.

PMID- 17516099
TI  - Identification of the porcine homologous of human disease causing trinucleotide
      repeat sequences.
AB  - Expansion in the repeat number of intragenic trinucleotide repeats (TNRs) is
      associated with a variety of inherited human neurodegenerative diseases. To study
      the composition of TNRs in a mammalian species representing an evolutionary
      intermediate between humans and rodents, we describe in this paper the
      identification of porcine noncoding and polyglutamine-encoding TNR regions and
      the comparison to the homologous TNRs from human, chimpanzee, dog, opossum, rat,
      and mouse. Several of the porcine TNR regions are highly polymorphic both within
      and between different breeds. The TNR regions are more conserved in terms of
      repeat length between humans and pigs than between humans and rodents suggesting
      that TNR lengths could be implicated in mammalian evolution. The TNRs in the
      FMR2, SCA6, SCA12, and Huntingtin genes are comparable in length to alleles
      naturally occurring in humans, and also in FMR1, a long uninterrupted CGG TNR was
      identified. Most strikingly, we identified a Huntingtin allele with 21
      uninterrupted CAG repeats encoding a stretch of 24 polyglutamines. Examination of
      this particular Huntingtin TNR in 349 porcine offspring showed stable
      transmission. The presence in the porcine genome of TNRs within genes that, in
      humans, can undergo pathogenic expansions support the usage of the pig as an
      alternative animal model for studies of TNR evolution, stability, and functional
      properties.

PMID- 17516100
TI  - Raking it in: the impact of enculturation on chimpanzee tool use.
AB  - Recent evidence for different tool kits, proposed to be based upon culture-like
      transmission, have been observed across different chimpanzee communities across
      Western Africa. In light of these findings, the reported failures by seven
      captive juvenile chimpanzees tested with 27 tool use tasks (Povinelli 2000) seem
      enigmatic. Here we report successful performance by a group of nine captive,
      enculturated chimpanzees, and limited success by a group of six semi-enculturated
      chimpanzees, on two of the Povinelli tasks, the Flimsy Tool task, and the Hybrid
      Tool task. All chimpanzees were presented with a rake with a flimsy head and a
      second rake with a rigid head, either of which could be used to attempt to
      retrieve a food reward that was out of reach. The rigid rake was constructed such
      that it had the necessary functional features to permit successful retrieval,
      while the flimsy rake did not. Both chimpanzee groups in the present experiment
      selected the functional rigid tool correctly to use during the Flimsy Tool task.
      All animals were then presented with two "hybrid rakes" A and B, with one half of
      each rake head constructed from flimsy, non-functional fabric, and the other half
      of the head was made of wood. Food rewards were placed in front of the rigid side
      of Rake A and the flimsy side of Rake B. To be successful, the chimps needed to
      choose the rake that had the reward in front of the rigid side of the rake head.
      The fully enculturated animals were successful in selecting the functional rake,
      while the semi-enculturated subjects chose randomly between the two hybrid tools.
      Compared with findings from Povinelli, whose non-enculturated animals failed both
      tasks, our results demonstrate that chimpanzees reared under conditions of semi
      enculturation could learn to discriminate correctly the necessary tool through
      trial-and-error during the Flimsy Tool task, but were unable to recognize the
      functional relationship necessary for retrieving the reward with the "hybrid"
      rake. In contrast, the enculturated chimpanzees were correct in their choices
      during both the Flimsy Tool and the Hybrid Tool tasks. These results provide the
      first empirical evidence for the differential effects of enculturation on
      subsequent tool use capacities in captive chimpanzees.

PMID- 17516101
TI  - Matching and oddity relational learning by pigeons (Columba livia): transfer from
      color to shape.
AB  - Relational learning, as opposed to perceptual learning, is based on the abstract
      properties of the stimuli. Although at present there is no doubt that pigeons are
      capable of relational behavior, this study aims to further disclose the
      conditions under which it occurs. Pigeons were trained in an outdoor cage on a
      matching-to-sample or an oddity-from-sample task, with colored cardboard stimuli
      presented horizontally. The apparatus involved three sliding lids on which the
      stimuli were drawn and which, when displaced, revealed the reinforcement. The
      lids were either adjacent to each other or somewhat separated. Training sessions
      involved two colors, and test sessions six different colors (same dimension
      test), or six different shapes (different dimension test). One group of birds
      trained under the 'adjacent' condition failed when tested with new stimuli, but
      succeeded in both dimension tests after training under the 'separate' condition.
      Two other groups of birds succeeded in all tests after training under the latter
      condition. These results show that depending on procedural details, pigeons are
      or are not able to transfer from one visual dimension to another, thus extending
      previous related findings.

PMID- 17516102
TI  - Clinical and molecular epidemiology of multidrug-resistant Citrobacter spp.
      infections in a French university hospital.

PMID- 17516103
TI  - Outbreak of Achromobacter xylosoxidans pseudobacteremia in a neonatal care unit
      related to contaminated chlorhexidine solution.

PMID- 17516104
TI  - Intestinal toxemia botulism in Italy, 1984-2005.
AB  - Botulism in humans is caused by botulinum neurotoxins, produced in most cases by
      Clostridium botulinum, although other Clostridia species are implicated as well.
      Of the five forms of botulism in humans, three are referred to as "infective":
      wound botulism, infant botulism, and adult intestinal botulism; the latter two
      forms are also referred to as "intestinal toxemia botulism" because the organism
      colonizes the lumen of the intestinal tract and produces botulinum neurotoxin in
      vivo. Twenty-three cases of infant botulism and three cases of adult intestinal
      botulism occurred in Italy between 1984 and 2005. Microbiological analyses of
      clinical, environmental, and food samples and analysis of clinical and
      epidemiological data revealed two main characteristics of intestinal toxemia
      botulism in Italy that are not common in cases in other countries: the isolation
      of a strain of C. butyricum that produced botulinum neurotoxin type E in 6 of 26
      cases, including two cases of adult intestinal toxemia botulism, and the onset of
      botulism in these cases with concomitant severe gastrointestinal symptomatology.
      This report summarizes the microbiological, clinical, and epidemiological data of
      all cases of intestinal toxemia botulism that have occurred in Italy in the
      period 1984-2005.

PMID- 17516105
TI  - Analysis of odorant-binding proteins in antennae of a geometrid species, Ascotis
      selenaria cretacea, which produces lepidopteran Type II sex pheromone components.
AB  - Information on the olfactory system in antennae of Geometridae moths is very
      limited, and odorant-binding proteins (OBPs) working as transporters of
      lipophilic odors have not been identified. In the first investigation on this
      family of insects, we examined antennal OBPs of the Japanese giant looper,
      Ascotis selenaria cretacea. RT-PCR experiments using several pairs of degenerate
      primers designed from known cDNA sequences encoding lepidopteran OBPs
      successfully amplified partial sequences of two pheromone-binding proteins
      (PBPs), named AscrPBP1 and AscrPBP2 in reference to their corresponding
      nucleotide sequence homologies with other PBPs. Using 5'- and 3'-rapid
      amplification of cDNA end strategies, a cDNA clone for AscrPBP1 encoding a
      protein of 141 amino acids was isolated. Western blotting with the antiserum
      against recombinant AscrPBP1 overexpressed in Escherichia coli showed that the
      AscrPBP1 gene was more strongly expressed in male antennae than in female
      antennae. Furthermore, natural AscrPBP1was isolated by immunoprecipitation with
      the antiserum, and its binding ability was evaluated by using synthetic sex
      pheromonal compounds with a C(19) chain. The result indicated that AscrPBP1 bound
      not only the pheromone components, 3,6,9-nonadecatriene and its 3,4-epoxy
      derivative, but also unnatural 6,7- and 9,10-epoxy derivatives. While no general
      odorant-binding proteins (GOBPs) were amplified in the RT-PCR experiments, two
      antisera prepared from GOBP1 and GOBP2 of Bombyx mori suggested the occurrence of
      at least two GOBPs in the A. s. cretacea antennae.

PMID- 17516106
TI  - Measuring quality of care in patients with multiple clinical conditions: summary
      of a conference conducted by the Society of General Internal Medicine.
AB  - Performance measurement has been widely advocated as a means to improve health
      care delivery and, ultimately, clinical outcomes. However, the evidence
      supporting the value of using the same quality measures designed for patients
      with a single clinical condition in patients with multiple conditions is weak. If
      clinically complex patients, defined here as patients with multiple clinical
      conditions, present greater challenges to achieving quality goals, providers may
      shun them or ignore important, but unmeasured, clinical issues. This paper
      summarizes the proceedings of a conference addressing the challenge of measuring
      quality of care in the patient with multiple clinical conditions with the goal of
      informing the implementation of quality measurement systems and future research
      programs on this topic. The conference had three main areas of discussion. First,
      the potential problems caused by applying current quality standards to patients
      with multiple conditions were examined. Second, the advantages and disadvantages
      of three strategies to improve quality measurement in clinically complex patients
      were evaluated: excluding certain clinically complex patients from a given
      standard, relaxing the performance target, and assigning a greater weight to some
      measures based on the expected clinical benefit or difficulty of reaching the
      performance target. Third, the strengths and weaknesses of potential novel
      measures such change in functional status were considered. The group concurred
      that, because clinically complex patients present a threat to the implementation
      of quality measures, high priority must be assigned to a research agenda on this
      topic. This research should evaluate the impact of quality measurement on these
      patients and expand the range of quality measures relevant to the care of
      clinically complex patients.

PMID- 17516107
TI  - Primary care resident perceived preparedness to deliver cross-cultural care: an
      examination of training and specialty differences.
AB  - OBJECTIVE: Previous research has shown that resident physicians report
      differences in training across primary care specialties, although limited data
      exist on education in delivering cross-cultural care. The goals of this study
      were to identify factors that relate to primary care residents' perceived
      preparedness to provide cross-cultural care and to explore the extent to which
      these perceptions vary across primary care specialties. DESIGN: Cross-sectional,
      national mail survey of resident physicians in their last year of training.
      PARTICIPANTS: Eleven hundred fifty primary care residents specializing in family
      medicine (27%), internal medicine (23%), pediatrics (26%), and
      obstetrics/gynecology (OB/GYN) (24%). RESULTS: Male residents as well as those
      who reported having graduated from U.S. medical schools, access to role models,
      and a greater cross-cultural case mix during residency felt more prepared to
      deliver cross-cultural care. Adjusting for these demographic and clinical
      factors, family practice residents were significantly more likely to feel
      prepared to deliver cross-cultural care compared to internal medicine, pediatric,
      and OB/GYN residents. Yet, when the quantity of instruction residents reported
      receiving to deliver cross-cultural care was added as a predictor, specialty
      differences became nonsignificant, suggesting that training opportunities better
      account for the variability in perceived preparedness than specialty.
      CONCLUSIONS: Across primary care specialties, residents reported different
      perceptions of preparedness to deliver cross-cultural care. However, this
      variation was more strongly related to training factors, such as the amount of
      instruction physicians received to deliver such care, rather than specialty
      affiliation. These findings underscore the importance of formal education to
      enhance residents' preparedness to provide cross-cultural care.

PMID- 17516108
TI  - Parathyroid subcutaneous pre-sternal transplantation after parathyroidectomy for
      renal hyperparathyroidism. Long-term graft function.
AB  - BACKGROUND: In the setting of total parathyroidectomy (TPT) and parathyroid
      transplantation (PTx) for renal hyperparathyroidism (RHP), we evaluated long-term
      parathyroid graft function after subcutaneous pre-sternal transplantation
      (SCPTx). Because parathyroid glands are surrounded by fatty tissue, we postulated
      that results of subcutaneous implantation of parathyroid tissue after total
      parathyroidectomy for renal hyperparathyroidism could be at least as successful
      as intramuscular grafting, but without its complications. PATIENTS AND METHODS:
      The study, a prospective open efficacy study of postoperative (po) diagnostic
      monitoring of intact parathyroid hormone (iPTH) on a cohort of surgical patients,
      was conducted within a university hospital with a dialysis unit. Thirty five
      patients (19 women and 16 men) operated on for renal hyperparathyroidism
      underwent TPT and SCPTx for RHP at the Department of General Surgery and the
      Department of Nephrology. Donostia Hospital. San Sebastian. Gipuzkoa. Spain, from
      January 2002 to December 2005. Follow-up ranges from 6 months to 42 months
      (median: 15.4 months). The main outcome measure was evaluation of graft function
      by measurement of iPTH plasma level, based on serum levels of iPTH before
      operation and 24 h and 1, 3, 5, 15, 30, 60, 100, and 150 weeks after surgery.
      RESULTS: Average preoperative iPTH values were 1,341.52 + 367.78 pg/ml (mean +/-
      SD) (range: 493-2,180). After TPT and PSCTx, iPTH levels became undetectable in
      all patients at 24 h. A level of 50 pg/ml was established as the criterion of
      adequate parathyroid graft function. Values obtained at the various time
      intervals were as follows: 14.14 + 7.73 1 pg/ml (mean +/- SD) (range: 6-36) after
      1 week, 53 + 77.33 pg/ml (mean +/- SD) (range: 35-74) after 5 weeks, 62.95 +
      20.93 pg/ml (mean +/- SD) (range: 11-89) after 15 weeks, 77.54 + 18.84 pg/ml
      (mean +/- SD) (range: 24.6-104.2) after 30 weeks, 109.29 + 50.22 pg/ml (mean +/-
      SD) (range: 54-327) after 60 weeks, 134.21 + 128.64 pg/ml (mean +/- SD) (range:
      43-712) after 100 weeks, and 122.84 + 117.54 pg/ml (mean +/- SD) (range: 68-723)
      after 150 weeks. Prevalence of hypoparathyroidism (intact parathyroid hormone
      serum level < 20 pg/ml with a normal or low serum calcium concentration) was 2/35
      (5.71%) by week 60 and recovered by week 100. Graft-related recurrence was 2.85%
      (1/35). CONCLUSIONS: Subcutaneous pre-sternal transplantation (SCPTx) after TPT
      and PTx for secondary (RHP) is an adequate method to replace muscular forearm
      parathyroid transplantation and avoid its complications. Functioning results of
      total parathyroidectomy and presternal subcutaneous grafting compare favorably
      with the published data on other surgical techniques proposed for the treatment
      of renal hyperparathyroidism. Results of long-term follow-up exceed previously
      reported results.

PMID- 17516109
TI  - Significance of CD44 expression in gastrointestinal stromal tumors in relation to
      disease progression and survival.
AB  - BACKGROUND: CD44 is a transmembrane glycoprotein belonging to the cell-adhesion
      molecule family. It has been identified as being involved in tumor progression
      and metastasis, and its expression has been found to be of prognostic
      significance in several human malignancies. The aim of this study was to assess
      CD44 expression in gastrointestinal stromal tumors (GISTs), the most common
      mesenchymal tumor of the gastrointestinal tract. METHODS: Between January 1995
      and March 2006, 92 patients undergoing surgical resection for GIST in National
      Cheng Kung University Hospital were evaluated. To study the significance of CD44
      expression, immunohistochemical staining of CD44 in tumor specimens was
      performed, and the clinicopathological information of patients was reviewed.
      RESULTS: Fifty-nine of 81 patients (73%) showed positive CD44 expression. Loss of
      CD44 expression was associated with disease progression (p = 0.019). Kaplan-Meier
      analysis revealed better progression-free survival among patients with strong
      CD44 expression (++ and +++) (p = 0.034), absence of disease progression (p <
      0.001), and lower risk, according to National Institutes of Health (NIH)
      Consensus Criteria for GIST risk stratification (p = 0.003). Multivariate
      analysis demonstrated that high-risk status was the only independent risk factor
      for disease progression and the only independent predictor for a poor progression
      free survival (p = 0.023 and 0.045, respectively). CONCLUSIONS: It is
      demonstrated that high-risk status by NIH criteria is significantly associated
      with disease progression and poor progression-free survival in GIST.

PMID- 17516110
TI  - Epidermal growth factor receptor (EGFR) expression is associated with a worse
      prognosis in gastric cancer patients undergoing curative surgery.
AB  - BACKGROUND: In gastric cancer, the recurrence rate is high even after curative
      surgery. A relevant issue is the identification of independent prognostic factors
      to select high-risk patients; such features can be used as predictive factors for
      tailored therapies. In this study we have investigated the role of epidermal
      growth factor receptor (EGFR) expression as a prognostic marker for predicting
      cancer behavior and clinical outcome in gastric cancer patients undergoing
      potentially curative surgery. METHODS: Epidermal growth factor receptor
      determination using a commercially available immunohistochemistry (IHC) kit was
      performed in tissues from 82 gastric cancer patients receiving primary surgical
      treatment and in 25 normal gastric mucosa specimens from noncancer patients. The
      EGFR positivity was correlated with disease recurrence and survival in univariate
      and multivariate analyses. RESULTS: Forty-four percent (36 cases) of gastric
      cancers were EGFR positive. In 66 curatively treated patients, EGFR expression
      correlated with disease recurrence and poorer survival in both univariate and
      multivariate analyses. In a multivariate model for predicting recurrence and
      survival, advanced tumor extension (T(3) or T(4)), nodal metastases, and EGFR
      expression were the only independent covariates. In particular, EGFR expression
      was shown to be a significant predictor of poor prognosis among gastric cancer
      patients having the same stage according to the current TNM staging system.
      CONCLUSIONS: These findings suggest that EGFR expression may be useful in
      identifying high-risk gastric cancer patients undergoing potentially curative
      surgery. Multimodal treatments should be considered in the adjuvant treatment of
      these patients.

PMID- 17516111
TI  - Emergency stenting of a ruptured infected anastomotic femoral pseudoaneurysm.
AB  - A 74-year-old man presented with a ruptured infected anastomotic femoral
      pseudoaneurysm. Due to severe medical comorbidities he was considered unsuitable
      for conventional surgical management and underwent an emergency endovascular
      repair with a balloon-expandable covered stent. The pseudoaneurysm was excluded
      successfully and the patient had an uneventful postoperative recovery with long
      term suppressive antimicrobials. He remained well for 10 months after the
      procedure with no signs of recurrent local or systemic infection and finally died
      from an acute myocardial infarction. To our knowledge, emergency endovascular
      treatment of a free ruptured bleeding femoral artery pseudoaneurysm has not been
      documented before in the English literature. This case illustrates that
      endovascular therapy may be a safe and efficient alternative in the emergent
      management of ruptured infected anastomotic femoral artery pseudoaneurysms when
      traditional open surgery is contraindicated.

PMID- 17516112
TI  - A rare cause of pulmonary emboli in a patient with deep vein thrombosis: Doppler
      ultrasonographic compressibility maneuver.

PMID- 17516113
TI  - Radioembolization with 90Y microspheres: angiographic and technical
      considerations.
AB  - The anatomy of the mesenteric system and the hepatic arterial bed has been
      demonstrated to have a high degree of variation. This is important when
      considering pre-surgical planning, catheterization, and trans-arterial hepatic
      therapies. Although anatomical variants have been well described, the
      characterization and understanding of regional hepatic perfusion in the context
      of radioembolization have not been studied with great depth. The purpose of this
      review is to provide a thorough discussion and detailed presentation of the
      angiographic and technical aspects of radioembolization. Normal vascular anatomy,
      commonly encountered variants, and factors involved in changes to regional
      perfusion in the presence of liver tumors are discussed. Furthermore, the
      principles described here apply to all liver-directed transarterial therapies.

PMID- 17516114
TI  - Expert and construct validity of the Simbionix GI Mentor II endoscopy simulator
      for colonoscopy.
AB  - OBJECTIVES: The main objectives of this study were to establish expert validity
      (a convincing realistic representation of colonoscopy according to experts) and
      construct validity (the ability to discriminate between different levels of
      expertise) of the Simbionix GI Mentor II virtual reality (VR) simulator for
      colonoscopy tasks, and to assess the didactic value of the simulator, as judged
      by experts. METHODS: Four groups were selected to perform one hand-eye
      coordination task (EndoBubble level 1) and two virtual colonoscopy simulations on
      the simulator; the levels were: novices (no endoscopy experience), intermediate
      experienced (<200 colonoscopies performed before), experienced (200-1,000
      colonoscopies performed before), and experts (>1,000 colonoscopies performed
      before). All participants filled out a questionnaire about previous experience in
      flexible endoscopy and appreciation of the realism of the colonoscopy
      simulations. The average time to reach the cecum was defined as one of the main
      test parameters as well as the number of times view of the lumen was lost.
      RESULTS: Novices (N = 35) reached the cecum in an average time of 29:57
      (min:sec), intermediate experienced (N = 15) in 5:45, experienced (N = 20) in
      4:19 and experts (N = 35) in 4:56. Novices lost view of the lumen significantly
      more often compared to the other groups, and the EndoBubble task was also
      completed significantly faster with increasing experience (Kruskal Wallis Test, p
      < 0.001). The group of expert endoscopists rated the colonoscopy simulation as
      2.95 on a four-point scale for overall realism. Expert opinion was that the GI
      Mentor II simulator should be included in the training of novice endoscopists
      (3.51). CONCLUSION: In this study we have demonstrated that the GI Mentor II
      simulator offers a convincing realistic representation of colonoscopy according
      to experts (expert validity) and that the simulator can discriminate between
      different levels of expertise (construct validity) in colonoscopy. According to
      experts the simulator should be implemented in the training programme of novice
      endoscopists.

PMID- 17516115
TI  - A comparative study of 10-Fr vs. 7-Fr straight plastic stents in the treatment of
      postcholecystectomy bile leak.
AB  - BACKGROUND: Biliary decompression is a key factor in the treatment of
      postcholecystectomy bile leak. However, the optimal size of the stent introduced
      by therapeutic endoscopic retrograde cholangiopancreatography (ERCP) is yet to be
      determined. The aim of the study was to compare the effectiveness of two straight
      plastic stents with different sizes (10-Fr and 7-Fr) in the treatment of
      postcholecystectomy bile leak. METHODS: Between January 2003 and August 2006, 63
      patients underwent therapeutic ERCP for postcholecystectomy bile leak. After
      visualization of the bile duct injury, endoscopic sphincterotomy was performed
      and the patients were randomized to receive either a 7-Fr (31 subjects, group A)
      or a 10-Fr (32 subjects, group B) straight plastic stent for four weeks. The
      success of the endoscopic treatment was determined by the elimination of the
      symptoms and the removal of the drain without any adverse outcomes. RESULTS: The
      endoscopic intervention was successful in 29 patients of group A (93.54%) and in
      31 patients of group B (96.87%). In the remaining two patients of group A, the 7
      Fr stent was substituted by a 10-Fr stent after 7 days because the leak remained
      unaffected, resulting in healing of the leaks. Surgery was required in the
      remaining one patient of group B. Eight patients developed post-ERCP pancreatitis
      (5 mild, 2 moderate, 1 severe), which was treated conservatively. CONCLUSIONS:
      This trial suggests that the stent size does not affect the outcome of the
      endoscopic intervention in postcholecystectomy bile leaks due to minor biliary
      tract injury; however, larger cohorts are required to confirm the optimal stent
      size in bile leaks due to major bile duct injury.

PMID- 17516116
TI  - Management of pancreatic pseudocyst in the era of laparoscopic surgery-
      experience from a tertiary centre.
AB  - BACKGROUND: In the era of minimally invasive surgery, laparoscopy has a great
      role to play in the management of pseudocyst of pancreas. We present our surgical
      experience over the past 12 years (May 1994 to April 2006) in the management of
      pancreatic pseudocysts. MATERIALS AND METHODS: The total number of cases was 108,
      with 76 male and 32 female patients. Age ranged from 18 to 70 years. Duration of
      symptoms ranged from 45 days to 7 months. Fifty-nine patients presented with pain
      abdomen. Sixty-one patients had co-morbid illness. Ten patients had abdominal
      mass on clinical examination. Predisposing factors were gallstones in 58 cases,
      alcohol in 20 cases, trauma in eight cases and post-pancreatectomy in one case.
      In 21 cases there are no predisposing factors. RESULTS: All the cases were
      successfully operated without any significant intraoperative complication.
      Laparoscopic cystogastrostomy was done in 90 cases (83.4%), laparoscopic
      cystojejunostomy in eight cases (7.4%), open cystogastrostomy in two cases
      (1.8%), and laparoscopic external drainage in eight cases (7.4%). Laparoscopic
      cholecystectomy was done in 47 cases along with the drainage procedure. The mean
      operating time was 95 minutes. Mean blood loss was 69 ml. Mean hospital stay was
      5.6 days. Percutaneous tube drain to assist decompression of the cyst was kept in
      all the laparoscopic cystojejunostomy (LCJ) group. Two patients were re-operated
      for bleeding and gastric outlet obstruction. We had no mortality in the
      postoperative period. With mean follow up of 54 months (range 3-145 months); only
      one patient who underwent laparoscopic cystogastrostomy (LCG) earlier in this
      series had recurrence due to inadequate stoma size. This patient later underwent
      OCG CONCLUSION: Laparoscopy has a significant role to play in the surgical
      management of pseudocysts with excellent outcome. It offers all the benefits of
      minimally invasive surgery to the patients.

PMID- 17516117
TI  - Knowledge and opinions regarding Medicare reimbursement for laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Medicare, via its fee schedule, determines amount of payment to
      physicians for services for its beneficiaries. Because many private insurance
      companies base their payment schedule on Medicare rates, it is important for
      physicians to know the rates of commonly performed procedures. In addition, it
      seems that public perception is that physicians receive substantial payments for
      procedures. This investigation explores patient, student, resident, and surgeon
      knowledge and opinion of Medicare reimbursements for laparoscopic
      cholecystectomy. METHODS: Patients, students, residents, and surgeons filled out
      an IRB-exempted survey. The survey included a written description of a
      laparoscopic cholecystectomy. All participants were asked to give their thoughts
      of what Medicare currently reimburses for a laparoscopic cholecystectomy ($622)
      and what they thought Medicare should reimburse for a laparoscopic
      cholecystectomy for our geographic area. RESULTS: There were 105 participants (47
      patients, 17 medical students, 33 surgical residents, and 8 attending surgeons)
      in the investigation. The reported mean reimbursements of what each group thought
      Medicare pays were patients, $9,396; students, $3,077; residents, $800; and
      surgeons, $711. The reported mean reimbursements of what each group thought
      Medicare should pay were patients, $8,067; students, $3,971; residents, $1,444;
      and surgeons, $1,600. The mean reimbursements were statistically different
      between all groups in both the amount Medicare currently pays and the amount
      Medicare should pay. CONCLUSION: Most of our participants overestimated what
      Medicare currently pays for laparoscopic cholecystectomy. Even the mean amount
      reported in the attending surgeon group was greater than the actual payment. All
      groups felt Medicare should pay more than the current rate; however, only
      patients thought Medicare should pay less than they currently pay (probably
      because of the incorrect perception of the current fee schedule).

PMID- 17516118
TI  - Influence of instrument size on endoscopic task performance in pediatric
      intracorporeal knot tying: smaller instruments are better in infants.
AB  - BACKGROUND: The widespread availability of adult minimal access surgical (MAS)
      equipment together with resource constraints have led pediatric surgeons to adopt
      the adult setup. This study examined the influence of instrument size on task
      outcome and physical impact on the surgeon in pediatric endoscopic intracorporeal
      knot tying. METHODS: Sixteen surgeons participated in this study in which they
      had to tie surgeon's knots inside a neonatal simulator box with an endoscopic
      field of 40 mm. All surgeons tied 20 knots using paired pediatric needle-holders
      and 20 knots using paired adult needle-holders in a randomized order. Knot
      quality score (KQS) and wrap length were used as indices of knot quality and wrap
      tightness. Electromyographic (EMG) recordings of the upper limb muscle groups
      were used to indicate muscular recruitment. A questionnaire on discomfort and
      instrument preference was also completed by the surgeons. RESULTS: A total of 640
      knots were analyzed. Median time was shorter for pediatric needle-holders than
      for adult needle-holders (94 s vs. 103 s; p < 0.001); however, KQS (0.271 vs.
      0.260; p = 0.509) and the tightness around the tube (86 mm vs. 86 mm; p = 0.255)
      were not significantly different. The proportion of knots that completely slipped
      was also similar for both needle-holders (19% vs. 22%; p = 0.322). The normalized
      EMG values when using adult needle-holders were significantly higher than when
      using pediatric needle-holders in all upper limb muscle groups with the exception
      of left forearm extensors (p = 0.460). The surgeons reported less discomfort with
      the pediatric needle-holders in the right forearm and hand, and 13 surgeons
      expressed overall preference for the smaller instruments. CONCLUSION: Endoscopic
      knot tying was performed faster in the neonatal simulator box using pediatric
      needle-holders while maintaining knot quality. Upper limb muscular recruitment
      was reduced resulting in less discomfort for the surgeon.

PMID- 17516119
TI  - Laparoscopic hepatectomy for hepatolithiasis: a feasibility and safety study in
      29 patients.
AB  - BACKGROUND: Hepatolithiasis is a prevalent disease in Southeast Asia. Hepatectomy
      was considered the best treatment for majority of cases. Laparoscopic hepatectomy
      is a new procedure for liver lesions that uses a minimal invasive approach. The
      aim of this study was to evaluate the feasibility and safety of laparoscopic
      hepatectomy for hepatolithiasis by comparing it with open hepatectomy. METHODS:
      From November 2002 to March 2006 a total of 30 consecutive patients underwent
      laparoscopic hepatectomy for hepatolithiasis in Sir Run Run Shaw Hospital. Twenty
      nine were included in this study (a converted case was excluded) and called the
      laparoscopic hepatectomy group (LH). During the same period 22 patients with
      hepatolithiasis who met the inclusion criteria for laparoscopic hepatectomy were
      selected for open hepatectomy and called the open group (OH). All operations were
      performed by the authors. There was no significant difference in preoperative
      data between the two groups. Data were statistically compared. RESULTS: Compared
      with open hepatectomy, those who underwent laparoscopic hepatectomy had a shorter
      postoperative hospital stay and fasting time, a lower postoperative serum
      aminotransferase level, and a higher postoperative serum albumin level. Stone
      clearance rate (intermediate rate, 89.7% vs. 86.4%; final rate, 100% vs. 96.5%),
      stone recurrence rate (0% vs. 4.5%), operating time, and intraoperative blood
      loss were similar for the two groups. Six complications occurred, two (6.8%) in
      LH and four (18.2%) in OH. There was no perioperative mortality in either group.
      CONCLUSION: Laparoscopic hepatectomy for hepatolithiasis is feasible and safe in
      selected patients.

PMID- 17516120
TI  - A randomized controlled study evaluating the effects of the temperature of
      insufflated CO2 on core body temperature and blood gases (an experimental study).
AB  - BACKGROUND: Heated carbon dioxide (CO2) was used for pneumoperitoneum (Pp) to
      prevent hypothermia. This study aimed to investigate the relationship between the
      temperature of the insufflated CO2 and blood gases together with the core body
      temperature (CBT). METHODS: A prospective controlled study was performed with 24
      pigs weighing approximately 20 kg randomized into four groups of 6 pigs each. A
      pneumoperitoneum at 12 mmHg of pressure was applied for 60 min with the pig under
      general anesthesia. The CO2)temperature was 22 degrees C in group 1, 37 degrees C
      in group 2, and 7 degrees C in group 3. In the "sham" group, pneumoperitoneum was
      not applied. Arterial blood pH and partial pressure of CO2 (PaCO2) were analyzed
      before insufflation, every 15 min during the pneumoperitoneum, and 15 min after
      the desufflation. The CBT was recorded before the insufflation, every 20 min
      during pneumoperitoneum, and 20 min after the desufflation. Blood gas analyses
      and CBT records for the "sham" group were performed at the same intervals.
      RESULTS: Arterial blood pH gradually decreased during pneumoperitoneum. At the
      60th minute of pneumoperitoneum, a minimum decrease in arterial blood pH (0.04; p
      = 0.027) and a minimum increase in PaCO2 (3.67; p = 0.027) were recorded in group
      3, whereas a maximum decrease in arterial blood pH (0.18; p = 0.027) and a
      maximum increase in PaCO2 (17.17; p = 0.027) were recorded in group 2. There was
      a significant negative correlation between PaCO2 and arterial blood pH in all the
      groups (r = -0.993; p < 0.01). The mean values of CBT decreases were
      statistically significant in all the groups: group 1 (p = 0.023), group 2 (p =
      0.026), group 3 (p = 0.026), and "sham" group (p = 0.024). CONCLUSIONS: The
      changes in PaCO2 were directly proportional and the changes in pH contrarily
      proportional to the temperature of the insufflated CO2. Significant differences
      in CBT decreases were found between the groups receiving heated gas and room
      temperature gas and the groups receiving heated gas and gas below room
      temperature.

PMID- 17516121
TI  - Precision in stitches: Radius Surgical System.
AB  - BACKGROUND: The Radius Surgical System is a manual manipulator with two
      additional degrees of freedom compared with conventional laparoscopic instruments
      (CLIs). This study aimed to compare the performance of laparoscopic suturing
      tasks with the use of the Radius Surgical System and CLIs, respectively. METHODS:
      Five experienced laparoscopic surgeons performed laparoscopic surgical tasks in a
      training box. The tasks consisted of knot-tying, suturing, and needle control
      tasks. The needle control task was performed to evaluate the precision of the
      needle drive by analysis of the needle exit point on a suture pad. In the knot
      tying and suturing tasks, required time and accuracy value were measured. Needle
      control tasks were performed on three different angulations of plane. The angles
      between the instrument plane and the target plane (AIT) were 30 degrees, 60
      degrees, and 90 degrees. The distance of the exit point to the center of the
      target field, the number of actions needed to fulfill a single task, and the
      required time were recorded and analyzed. RESULTS: In the knot-tying and frontal
      suturing tasks, there were no significant differences between the two groups. In
      the sagittal suturing task, the required time in the Radius group was
      significantly shorter than in the CLI group. In the needle control tasks on 30
      degree and 60 degree AIT, the distance was significantly shorter in the Radius
      group than in the CLI group. There were no significant differences in the number
      of actions or the required time. In the frontal and sagittal needle control task
      on 90 degree AIT, the distance was significantly shorter in the Radius group than
      in the CLI group. The number of actions and the required time were significantly
      less in the Radius group than in the CLI group. CONCLUSIONS: The two additional
      degrees of freedom contributed to accurate and controlled needle guidance,
      especially in difficult spatial situations.

PMID- 17516122
TI  - Laparoscopic cholecystectomy versus mini-laparotomy cholecystectomy: a meta
      analysis of randomised control trials.
AB  - AIMS: To use meta-analytic techniques to compare peri-operative and short term
      post-operative outcomes for patients undergoing cholecystectomy via the
      laparoscopic or mini-open approach. METHODS: Randomised control trials published
      between 1992 and 2005, cited in the literature of elective laparoscopic (LC)
      versus mini-open cholecystectomy (MoC) for symptomatic gallstone disease were
      included. End points evaluated were adverse events, operative and functional
      outcomes. A random effects meta-analytical model was used and between-study
      heterogeneity assessed. Subgroup analysis was performed to evaluate the
      difference in results for study size and quality and data reported from 2000.
      RESULTS: Nine randomised studies of 2032 patients were included in the analysis.
      There was considerable variation in the size and type of incision used for MoC in
      the studies. There was a significantly longer operating time for the LC group, by
      14.14 minutes (95% CI 2.08, 26.19; p < 0.0001). Length of stay was reduced in the
      LC group by 0.37 days (95% CI -0.53, -0.21; p < 0.0001), with no significant
      heterogeneity for either outcome. For all other operative and post-operative
      outcomes, there was no significant difference between the two groups. CONCLUSION:
      MoC appeared to have similar outcomes compared to LC, however LC did reduce the
      length of hospital stay. MoC is a viable and safe option for healthcare providers
      without the financial resources for laparoscopic equipment and appropriately
      trained surgical teams.

PMID- 17516123
TI  - Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory
      cytokines via activation of ERK and NF-kappaB.
AB  - The ototoxicity of cisplatin, a widely used chemotherapeutic agent, involves a
      number of mechanisms, including perturbation of redox status, increase in lipid
      peroxidation, and formation of DNA adducts. In this study, we demonstrate that
      cisplatin increased the early immediate release and de novo synthesis of
      proinflammatory cytokines, including TNF-alpha, IL-1beta, and IL-6, through the
      activation of ERK and NF-kappaB in HEI-OC1 cells, which are conditionally
      immortalized cochlear cells that express hair cell markers. Both neutralization
      of proinflammatory cytokines and pharmacologic inhibition of ERK significantly
      attenuated the death of HEI-OC1 auditory cells caused by cisplatin and
      proinflammatory cytokines. We also observed a significant increase in the protein
      and mRNA levels of proinflammatory cytokines in both serum and cochleae of
      cisplatin-injected rats, which was suppressed by intraperitoneal injection of
      etanercept, an inhibitor of TNF-alpha. Immunohistochemical studies revealed that
      TNF-alpha expression was mainly located in the spiral ligament, spiral limbus,
      and the organ of Corti in the cochleae of cisplatin-injected rats. NF-kappaB
      protein expression, which overlapped with terminal deoxynucleotidyl transferase
      mediated dUTP nick-end-labeling-positive signal, was very strong in specific
      regions of the cochleae, including the organ of Corti, spiral ligament, and stria
      vascularis. These results indicate that proinflammatory cytokines, especially TNF
      alpha, play a central role in the pathophysiology of sensory hair cell damage
      caused by cisplatin.

PMID- 17516124
TI  - Intrapatient comparison of 2-deoxy-2-[F-18]fluoro-D-glucose with positron
      emissiontomography/computed tomography to Tc-99m fanolesomab (NeutroSpec) for
      localization of infection.
AB  - PURPOSE: This study evaluated the efficacy of 2-deoxy-2-[F-18]fluoro-D: -glucose
      (FDG) with positron emission tomography/computed tomography (PET/CT) in
      comparison with Tc-99m fanolesomab (NeutroSpec) for imaging infection.
      PROCEDURES: Twelve patients with possible infection were studied with both FDG
      PET/CT and Tc-99m fanolesomab. One patient was studied twice for a total of 13
      paired studies. The final determination of the presence or absence of infection
      and the site(s) of infection at the time of imaging was made by an infectious
      disease physician using culture results and other relevant information. The
      sensitivity, specificity, and accuracy were calculated for each imaging study on
      a per paired study basis and a per lesion basis. In addition, the quality of
      lesion depicted was compared between the two studies. RESULTS: Three patients
      were determined not to have infection. Ten paired studies, in nine patients, were
      determined to have one or more sites of infection: seven had one site and three
      had two sites. On a per paired study basis the sensitivity, specificity, and
      accuracy of FDG-PET/CT were all 100%; for Tc-99m fanolesomab these parameters
      were 30, 100, and 46%, respectively (P < 0.01 for sensitivity and accuracy). On a
      per site basis the results for FDG-PET/CT were all 100% and for Tc-99m
      fanolesomab they were 23, 100, and 38% (P < 0.01 for sensitivity and accuracy).
      In the three sites of infection shown by both studies, FDG-PET/CT was judged to
      be superior in spatial resolution and anatomic localization compared to Tc-99m
      fanolesomab in all three sites. CONCLUSION: FDG-PET/CT is superior to Tc-99m
      fanolesomab for detecting and localizing sites of infection.

PMID- 17516125
TI  - Species identification of animal cells by nested PCR targeted to mitochondrial
      DNA.
AB  - We developed a highly sensitive and convenient method of nested polymerase chain
      reaction (PCR) targeted to mitochondrial deoxyribonucleic acid (DNA) to identify
      animal species quickly in cultured cells. Fourteen vertebrate species, including
      human, cynomolgus monkey, African green monkey, mouse, rat, Syrian hamster,
      Chinese hamster, guinea pig, rabbit, dog, cat, cow, pig, and chicken, could be
      distinguished from each other by nested PCR. The first PCR amplifies
      mitochondrial DNA fragments with a universal primer pair complementary to the
      conserved regions of 14 species, and the second PCR amplifies the DNA fragments
      with species-specific primer pairs from the first products. The species-specific
      primer pairs were designed to easily distinguish 14 species from each other under
      standard agarose gel electrophoresis. We further developed the multiplex PCR
      using a mixture of seven species-specific primer pairs for two groups of animals.
      One was comprised of human, mouse, rat, cat, pig, cow, and rabbit, and the other
      was comprised of African green monkey, cynomolgus monkey, Syrian hamster, Chinese
      hamster, guinea pig, dog, and chicken. The sensitivity of the PCR assay was at
      least 100 pg DNA/reaction, which was sufficient for the detection of each species
      of DNA. Furthermore, the nested PCR method was able to identify the species in
      the interspecies mixture of DNA. Thus, the method developed in this study will
      provide a useful tool for the authentication of animal species.

PMID- 17516126
TI  - Matrix and TGF-beta-related gene expression during human dental pulp stem cell
      (DPSC) mineralization.
AB  - We have recently reported the induction of dental pulp stem cells (DPSCs) into
      dentin-secreting odontoblast-like cells after stimulation by isolated dentin
      matrix components, thus mimicking the nature of tissue regeneration seen after
      tooth disease and injury. After confluency, the cells were further cultured for
      21 d in the 10% fetal bovine serum (FBS) Dulbecco's modified Eagle's medium
      (DMEM) (control), and in this medium, with the addition of dentin extract (DE)
      and the mineralization supplement (MS) of ascorbic acid and beta-glycerophosphate
      (treatment). To identify genes associated with this process, specimens were
      analyzed with a HG-U133A human gene chip and Arrayassist software. A total of 425
      genes, among them 21 matrix and eight TGF-beta-related genes, were either up- or
      downregulated in the experimental group in which the cells showed odontoblast
      like differentiation and mineralization. Expression of selected genes was further
      confirmed by real-time polymerase chain reaction (PCR) analysis. Of the
      extracellular matrix (ECM)-related genes, two types of collagen genes were
      upregulated and seven others downregulated. Other ECM-related genes, for example
      fibulin-1, tenascin C, and particularly thrombospondin 1, were upregulated, and
      fibulin-2 was downregulated. Most noticeably, the matrix metalloproteinase 1 was
      induced by the treatment. In the TGF-beta superfamily, upregulation of the type
      II receptor, endoglin, and growth/differentiation factor 5 was coordinated with
      the downregulation of activin A, TGF-beta2, and TGF-beta1 itself. This study
      identifies the matrix and TGF-beta-related gene profiles during the DPSC cell
      mineralization in which several genes are reported for the first time to be
      associated with this process, thus greatly expanding our molecular knowledge of
      the induced disease repair process.

PMID- 17516127
TI  - Maternal and fetal outcomes of 72 pregnancies in Argentine patients with systemic
      lupus erythematosus (SLE).
AB  - The purpose of the following study was to analyze maternal and fetal outcomes in
      pregnant patients with systemic lupus erythematosus (SLE) and the influence of
      SLE exacerbations on those pregnancies. Seventy-two pregnancies in 61 SLE
      patients treated between January 1986 and February 2004 in Hospital de Clinicas
      "Jose de San Martin" were reviewed retrospectively. Patient age was 28.1 +/- 6.2
      years (mean+/-standard deviation [SD]). Mean SLE duration was 4.5 +/- 3.2 years
      (range 6 months-10 years). No patient acquired the disorder during gestation.
      Four (5.5%) patients had signs of active disease at the beginning of her
      pregnancy. Sixteen patients, accounting for 20 pregnancies, had a history of
      lupus nephritis. Nine patients met secondary antiphospholipid syndrome criteria
      and had 13 pregnancies. There were 14 exacerbations of the disease during
      pregnancy (19.4%), with most flares being mild. The most common obstetric
      complications were gestational hypertension in 15 pregnancies (20.8%) and
      preeclampsia in 8 pregnancies (11%). Forty-six percent of pregnancies ended in
      preterm deliveries. There were 62 live births (1 twin birth; 85%), 6 stillbirths
      (8%), and 5 spontaneous abortions (7%). Thirty-nine percent of newborns had low
      birth weight. Adequate pregnancy follow-up and delivery care by an
      interdisciplinary team in Argentine SLE patients with no pre-gestational
      preparation resulted in maternal and fetal outcomes similar to those seen in
      world reference centers.

PMID- 17516128
TI  - Steady improvement of prothrombin levels after cyclophosphamide therapy in
      pediatric lupus anticoagulant hypoprothrombinemia syndrome (LAHPS).
AB  - Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare acquired
      disorder associated with several different conditions but mostly with systemic
      lupus erythematosus (SLE). LAHPS probably results from the presence of anti
      Factor II antibodies, which usually counterbalance the prothrombotic effect of
      the lupus anticoagulant (LAC). In fact, Factor II deficiency in SLE is invariably
      associated with the presence of LAC. No consensus exists for the treatment of
      LAHPS. Corticosteroids, with or without the addition of vitamin K or blood
      products, have been a successful first-line treatment. Immunoglobulin (IVIG)
      treatment has been shown to be effective in the setting of acute bleeding.
      However, in some patients, conservative treatment is not enough to control
      bleeding, and the addition of immunosuppressive therapy, usually azathioprine, is
      needed. In our patients, Factor II deficiency reappeared after tapering steroids.
      Both children achieved normal Factor II levels with cyclophosphamide. This effect
      was long-lasting, a phenomenon that has not been documented in children prior to
      this report.

PMID- 17516129
TI  - Clinical and serological correlates of antinucleosome antibodies in South
      Africans with systemic lupus erythematosus.
AB  - Antinucleosome antibodies (AnuA) are increasingly recognized as an important
      biomarker in the diagnosis and subset stratification of patients with systemic
      lupus erythematosus (SLE). The aim of the study was to determine the sensitivity,
      specificity, and clinico-serological correlates of AnuA in black South Africans
      with SLE. We performed a cross-sectional study of 86 SLE patients attending a
      tertiary center and 87 control subjects. AnuA were tested using a second
      generation enzyme-linked immunosorbent assay (ELISA). The sensitivity,
      specificity, positive predictive value, and negative predictive value of AnuA
      were 45.3, 94.3, 88.6, and 63.6%, respectively. The presence of AnuA were
      strongly associated with the co-presence of anti-dsDNA antibodies (OR = 3.4, p <
      0.0005) and antihistone antibodies (OR = 15.7, p < 0.00001). Patients who were
      seropositive for AnuA were more likely to have skin involvement (discoid lupus
      and/or malar rash) and had higher SLE disease activity index (SLEDAI) scores and
      Systemic Lupus International Collaborative Clinics/American College of
      Rheumatology (SLICC/ACR) damage scores (p < 0.05). IgG anticardiolipin antibody
      (aCL) levels showed a significant correlation with AnuA ratios (p < 0.01). Our
      findings provide further evidence that AnuA are a sensitive and specific
      diagnostic biomarker in SLE. Moreover, our finding that the presence of AnuA, but
      not anti-dsDNA antibodies, are associated with worse SLICC/ACR damage scores
      suggest that AnuA may have a role in predicting disease outcome. The correlation
      between IgG aCL and AnuA is a novel finding that merits further studies to
      determine possible common peptide specificities of the antibodies.

PMID- 17516130
TI  - The forgotten ureteric JJ stent and its prevention: a prospective audit of the
      value of a ureteric stent logbook.
AB  - BACKGROUND: Temporary ureteric stent insertion is an integral part of modern endo
      urological practice. Delayed stent removal or forgotten stents are associated
      with increased patient morbidity and complications which are often difficult to
      manage. METHODS AND RESULTS: We prospectively audited our ureteric stent
      insertion and removal logbook system to determine the value and effectiveness of
      our stent follow-up. Over a 1-year period, 210 ureteric stents were inserted in
      our urological unit. Of these, 47 (22.4%) patients were unaccounted as having
      their stents removed within the stent logbooks. One patient was lost to follow-up
      and re-presented with stent encrustation 10 months later. CONCLUSIONS: Our
      results in this audit suggest that our system of ureteric stent follow-up is not
      effective. We have now introduced a new system that we feel is a safer and a
      satisfactory alternative to the stent logbooks. This includes a patient education
      leaflet and removal date scheduling prior to discharge from hospital.

PMID- 17516131
TI  - Perforated retrocaecal appendix presenting as right lumbar abscess.
AB  - BACKGROUND: Acute appendicitis is common in older patients, however, the
      presentation may differ from the younger population and it is often complicated
      by coexistent disease and delays in presentation. AIMS: This case report
      describes an unusual presentation of acute appendicitis in an elderly patient and
      also demonstrates a unique anatomical pathway of disease extension. In addition,
      this case report highlights the advantages of CT in preoperative evaluation and
      subsequent management of these protean presentations of acute appendicitis.
      METHODS: This report describes a case of an asymptomatic retrocaecal perforated
      appendicitis which presented clinically as a right lumbar abscess with
      surrounding cellulitis, and was further complicated by a concomitant new
      diagnosis of type 2 diabetes mellitus in a 66-year-old male. CONCLUSION: Elderly
      or immunocompromised patients presenting with cellulitis or a cutaneous abscess
      of the abdominal wall or lumbar region may benefit from an abdominal CT to
      demonstrate an intraperitoneal source of sepsis.

PMID- 17516132
TI  - Description of joint movements in human and non-human primate locomotion using
      Fourier analysis.
AB  - To describe and help interpret joint movements in various forms of primate
      locomotion, we explored the use of Fourier analysis to represent changing joint
      angles as a series of sine and cosine curves added together to approximate the
      raw angular data. Results are presented for four joints (shoulder, elbow, hip and
      knee) with emphasis on the shoulder, and for five types of locomotion (catarhine
      primate quadrupedal walking, human hands-and-feet creeping and hands-and-knees
      creeping, and human walking and running). Fourier analysis facilitates functional
      interpretation of the angles of all four joints, by providing average joint
      angles and an indication of the number of peaks and troughs in the angular data.
      The description of limb movements also afforded us the opportunity to compare
      human and other catarhine joint angles, and we interpret the Fourier results in
      terms of locomotor posture and type. In addition, the shoulder data are useful
      for determination of some aspects of interlimb coordination. Non-human primates
      walking quadrupedally and humans creeping on hands and knees generally evince
      diagonal couplets interlimb coordination, in which the hand on one side strikes
      the substrate at about the same time as the contralateral foot or knee.
      Furthermore, human walking and running seem to follow a similar pattern, as
      indicated by Fourier analysis. From our data it is concluded that human bipedal
      gaits are qualitatively similar to diagonal couplets gaits in other primates, but
      quite different from the lateral couplets gaits used by many non-primate mammals.
      A number of other benefits of Fourier analysis in primate locomotion studies are
      also discussed. These include the ability to make statistical comparisons among
      various types of limb movements in a wide variety of species, a simple archival
      technique for limb movement data, and a greater understanding of the variability
      of locomotor movements.

PMID- 17516133
TI  - Effects of male group size, parity, and cycle stage on female chimpanzee
      copulation rates at Ngogo, Kibale National Park, Uganda.
AB  - Chimpanzees have complex and variable mating strategies, but most copulations
      occur when females with full sexual swellings are in parties with multiple males
      and mate with most or all of those males. Daily copulation rates for fully
      swollen females vary at different times of a female's cycle, among females, and
      across communities and populations. Variation in female age, parity, and cycle
      stage underlie some of this variation, but possible demographic effects on
      copulation rates have not been systematically investigated. Demographic variation
      can affect many aspects of behavior and ecology, including the frequency and
      success of different mating tactics. Analysis of data from the unusually large
      chimpanzee community at Ngogo produces two results that are consistent with the
      hypothesis that demographic variation affects female copulation rates. Copulation
      rates were high compared with those reported from other research sites, where
      females had fewer potential mates available. Daily copulation rates of fully
      swollen females were also positively related to the number of males with whom
      they associated. Ngogo data also re-confirm results from other studies, of both
      wild and captive populations, showing that female copulation rates increase
      during periovulatory periods. This is consistent with the hypothesis that sexual
      swellings and extended receptivity and proceptivity help to protect females
      against infanticide by helping to ensure they mate with all potential sires. As
      at some other sites, parous females at Ngogo copulated at higher rates than
      nulliparous females. Possible effects of demography on sexual behavior should be
      considered in assessments of differences between chimpanzees and bonobos and of
      variation across chimpanzee populations.

PMID- 17516134
TI  - A cytosolic NADP-malic enzyme gene from rice (Oryza sativa L.) confers salt
      tolerance in transgenic Arabidopsis.
AB  - NADP-malic enzyme (NADP-ME, EC 1.1.1.40) functions in many different pathways in
      plant and may be involved in plant defense such as wound and UV-B radiation.
      Here, expression of the gene encoding cytosolic NADP-ME (cytoNADP-ME, GenBank
      Accession No. AY444338) in rice (Oryza sativa L.) seedlings was induced by salt
      stress (NaCl). NADP-ME activities in leaves and roots of rice also increased in
      response to NaCl. Transgenic Arabidopsis plants over-expressing rice cytoNADP-ME
      had a greater salt tolerance at the seedling stage than wild-type plants in MS
      medium-supplemented with different levels of NaCl. Cytosolic NADPH/NADP(+)
      concentration ratio of transgenic plants was higher than those of wild-type
      plants. These results suggest that rice cytoNADP-ME confers salt tolerance in
      transgenic Arabidopsis seedlings.

PMID- 17516135
TI  - [Redescription of the species of Calyptrobothrium Monticelli, 1893
      (Tetraphyllidea: Phyllobothriidae) parasites of Torpedo marmorata in Torpedo
      nobiliana (Elasmobranchii: Torpedinidae)].
AB  - A study of the cestodes from the intestinal parasites of torpedinid elasmobranchs
      off the coast of Algeria, revealed the presence, in Torpedo marmorata Risso, of a
      species of Calyptrobothrium Monticelli, 1893, which we believe is identical to C.
      riggii Monticelli, 1893. This species, which has not been re-examined since its
      original description, is redescribed. We consider that the cestode from T.
      marmorata, described by Zschokke (1888) under the name of Tetrabothrium
      longicolle Molin, 1858, is conspecific with C.riggii. In Torpedo nobiliana
      Bonaparte, from the Mediterranean, we found C. occidentale Linton, 1900 and C.
      minus Linton, 1907. These two species are redescribed based on the type-material
      from the North American Atlantic coast, as well as from specimens collected off
      Sete and Algeria. We place several specimens, previously identified as C. riggii,
      as conspecific with C. minus. An amended diagnosis for Calyptrobothrium is
      proposed. We discuss the attribution of Bilocularia hyperapolytica Obersteiner,
      1914 from Centrophorus granulosus (Centrophoridae) to Calyptrobothrium. C.
      chalarosomum Alexander, 1963 from Cephaloscyllium isabellum (Scylliorhinidae) off
      New-Zealand is excluded from the genus and placed close to Crossobothrium Linton,
      1889.

PMID- 17516136
TI  - Genetic variation in the endangered Anisodus tanguticus (Solanaceae), an alpine
      perennial endemic to the Qinghai-Tibetan Plateau.
AB  - We used random amplified polymorphic DNA markers (RAPDs) to assess genetic
      variation between- and within-populations of Anisodus tanguticus (Solanaceae), an
      endangered perennial endemic to the Qinghai-Tibetan Plateau with important
      medicinal value. We recorded a total of 92 amplified bands, using 12 RAPD
      primers, 76 of which (P=82.61%) were polymorphic, and calculated values of H(t)
      and H(sp) of 0.3015 and 0.4459, respectively, suggesting a remarkably high rate
      of genetic variation at the species level. The average within-population
      diversity also appeared to be high, with P, H(e) and H(pop) values of 55.11%,
      0.1948 and 0.2918, respectively. Analyses of molecular variance (AMOVA) showed
      that among- and between-population genetic variation accounted for 67.02% and
      32.98% of the total genetic variation, respectively. In addition, Nei's
      coefficient of differentiation (G(ST)) was found to be high (0.35), confirming
      the relatively high level of genetic differentiation among the populations. These
      differentiation coefficients are higher than mean corresponding coefficients for
      outbreeding species, but lower than reported coefficients for some rare species
      from this region. The genetic structure of A. tanguticus has probably been shaped
      by its breeding attributes, biogeographic history and human impact due to
      collection for medicinal purposes. The observed genetic variations suggest that
      as many populations as possible should be considered in any planned in situ or ex
      situ conservation programs for this species.

PMID- 17516137
TI  - Cartilage polysaccharide induces apoptosis in human leukemia K562 cells.
AB  - In this study, we extracted a polysaccharide (short-chain polysaccharide [PS])
      from porcine cartilage and examined its function in chronic myeloid leukaemia by
      using human K562 cells and mouse L1210 cells. Results of cell proliferation assay
      indicated that PS inhibited cancer cell growth at different concentrations, while
      it had little effect on normal cells. The presence of morphological aspects of
      apoptosis, such as nuclear shrinkage, was shown in H&E stained sections. The
      occurrence of PS-induced apoptosis was confirmed by TUNEL assay and cell cycle
      analysis. The results of immunofluorescent staining indicated the molecular
      mechanism underlying. Through interfering with the cell cycle of tumor cells, PS
      may induce apoptosis by downregulating the expression level of cyclin D1 and
      upregulating the level of p21 protein. Correlation analysis of apoptosis and MAPK
      suggested that inactivation of ERK was crucial for PS induced apoptosis, while
      JNK phosphorylation had a small effect and p38 was not involved. In vivo assay
      showed that PS inhibited L1210 cell growth in vivo and prolonged the life span of
      L1210-bearing mice. We conclude that PS is a polysaccharide with anticancer
      effects and induced apoptosis in human K562 cells.

PMID- 17516138
TI  - Comparison of ALAD activities of Citrobacter and Pseudomonas strains and their
      usage as biomarker for Pb contamination.
AB  - Delta-aminolevulinate dehydratase (ALAD) activity has been used in prokaryotes
      and eukaryotes as a biomarker for environmental lead (Pb) exposure and toxicity.
      Microorganisms are sensitive indicators of toxicity at the fundamental level of
      ecological organization, but bacterial biomarker studies are focused on the
      Pseudomonas strains in Group I and E coli. The objectives of the present work
      were to determine if Burkholderia gladioli belonging to group II, due to its
      16SrRNA similarity, can be used as biomarker in metal contamination and compare
      its possible usage with Pseudomonas aeruginosa and Citrobacter freundii
      (previously known as Esherichia freundii) and Bacterium freundii which are
      classified in Group I. In this study, ALAD activity in an environmental strains
      of Burkholderia gladioli, Pseudomonas aeruginosa, Citrobacter freundii were
      investigated to evaluate potential inhibition by Pb and other toxic metals. When
      the ALAD activity of Burkholderia gladioli was tested, Co and Pb decreased
      activity by 27 and 71%, respectively. In addition to these findings, Zn increased
      the activity up to 26%. These effects were found to be statistically meaningful
      (p < 0.05). It was determined that the increase of lead concentration inhibites
      the ALAD activity at each of the three strains. There was a statistically
      significant dose-response relationship between ALAD activity in cells of
      Burkholderia gladioli and Pb (Pearson correlation coefficent = -0.665; r(2) =
      0.665, and p < 0.001). The strongest ALAD inhibition which was measured was 90%
      at Burkholderia gladioli when protein extracts were incubated with 750 muM of Pb.
      The relationship between Pb and ALAD activity was statistically described by
      [ALAD Activity] = 0.476-0.000597 x [Pb]. According to the obtained results, we
      suggest that the ALAD of Burkholderia gladioli can be used as a biomarker for
      lead contamination in the environment.

PMID- 17516139
TI  - Mapping giant salvinia with satellite imagery and image analysis.
AB  - QuickBird multispectral satellite imagery was evaluated for distinguishing giant
      salvinia (Salvinia molesta Mitchell) in a large reservoir in east Texas. The
      imagery had four bands (blue, green, red, and near-infrared) and contained 11-bit
      data. Color-infrared (green, red, and near-infrared bands), normal color (blue,
      green and red bands), and four-band composite (blue, green, red, and near
      infrared bands) images were studied. Unsupervised image analysis was used to
      classify the imagery. Accuracy assessments performed on the classification maps
      of the three composite images had producer's and user's accuracies for giant
      salvinia ranging from 87.8 to 93.5%. Color-infrared, normal color, and four-band
      satellite imagery were excellent for distinguishing giant salvinia in a complex
      field habitat.

PMID- 17516140
TI  - Liver lesions in demersal fishes near a large ocean outfall on the San Pedro
      Shelf, California.
AB  - The prevalence of toxicopathic liver lesions in demersal fish on the San Pedro
      Shelf, California was determined for a 15-year period (1988-2003). Fish livers
      were sampled at fixed locations as part of the Orange County Sanitation Districts
      (OCSD) ocean monitoring program. Histopathological examination of selected fish
      liver tissues was studied to determine whether the wastewater discharge had
      affected fish health. The prevalence of toxicopathic lesion classes neoplasms
      (NEO), preneoplastic foci of cellular alteration (FCA), and hydropic vacuolation
      (HYDVAC) varied among species and locations. For all species sampled, severe
      lesions occurred in 6.2% of the fish examined (n=7,694). HYDVAC (4.1%) was the
      most common toxicopathic lesion type followed by FCA (1.4%) and NEO (0.7%).
      HYDVAC occurred only in white croaker (Genyonemus lineatus), accounting for 84.8%
      of the toxicopathic lesions for this species. Prevalence of HYDVAC, NEO, and FCA
      in white croaker was 15.2, 2.0, and 0.7%, respectively. The prevalence of HYDVAC
      and NEO in white croaker increased with age and size but there was no sexual
      difference. A linear regression model was used for hypothesis testing to account
      for significant differences in fish size (and age for croakers) at the different
      sampling locations. This analysis showed that for HYDVAC there was no spatial or
      location effect for lesion rate or size/age of onset. For NEO, the model
      predicted that white croaker near the wastewater outfall may acquire these
      lesions at a smaller size/younger age, and at a higher rate, than at other sites.
      However, this result may be biased due to the unequal size frequency
      distributions and the low prevalence of NEO in white croaker at the different
      sampling sites. Bigmouth sole (Hippoglossina stomata) had a prevalence of FCA and
      NEO of 1.3 and 0.35%, respectively, but the prevalence and distribution of
      lesions was too few for statistical testing. There was no sexual difference for
      lesion prevalence in hornyhead turbot (Pleuronichthys verticalis) and the
      prevalence of FCA and NEO was 3.4 and 0.37%, respectively. FCA prevalence
      increased with size in hornyhead turbot and there were no significant spatial
      differences for lesion rates and fish size at lesion onset. Overall, consistent
      spatial differences for lesion prevalence were not demonstrated and highlight the
      analytical difficulties of detecting a possible point source impact when the
      effect is rare, correlated with the size/age structure of the population, and may
      be caused by exposure to unknown multiple sources. Thus, the usefulness of liver
      histopathology as a point-source monitoring tool is best applied to where the
      spatial scale of impact generally exceeds the home range of the target species.

PMID- 17516141
TI  - Phosphorus fractions and adsorption characteristics of floodplain sediments in
      the lower reaches of the Hanjiang River, China.
AB  - The phosphorus fractions and adsorption characteristics of seven floodplain
      sediment samples collected in the lower reaches of China's Hanjiang River were
      studied. Most phosphorus fractions showed a marked downstream increase in
      response to point-source inputs from urban areas. Total phosphorus (TP) contents
      in the sediments ranged from 603.68 to 945.25 mg x kg(-1). Inorganic phosphorus
      (IP) was the major component of TP, and calcium-bound phosphorus (Ca-P) was the
      major fraction of IP. The distribution characteristics of the phosphorus contents
      were affected by sediment grain size and hydrodynamic conditions. The maximum
      phosphorus adsorption capacities (Q (max)) and the half-saturation concentration
      (k) were obtained using an improved Langmuir model. Native adsorbed exchangeable
      phosphorus content (w (NAP)) and the zero-equilibrium phosphorus concentration
      value (c (EPC0)) were subsequently calculated. The effects of sediment grain
      size, temperature, and disturbance on the phosphorus adsorption isotherms were
      also studied. The results showed that phosphorus adsorption on floodplain
      sediments was primarily chemisorption; the particle concentration effect played a
      more important role at a disturbance intensity of 150 r x min(-1) (on a shaker
      table) than at 100 r x min(-1).

PMID- 17516142
TI  - Bovine recombinant IFNgamma induces endothelial cell gene transcription of
      immunoregulatory molecules and upregulates PMN and PBMC adhesion on bovine
      endothelial cells.
AB  - Interferon gamma (IFNgamma) is an important modulator of immune responses acting
      on multiple cell types, such as lymphocytes, macrophages or endothelial cells. We
      investigated the effects of recombinant bovine IFNgamma on bovine umbilical vein
      endothelial cells (BUVEC) for the level of polymorphonuclear neutrophil cell
      (PMN)- and peripheral blood mononuclear cell (PBMC)-adhesion as well as the gene
      transcription of endothelial cell-derived adhesion molecules (E-selectin, P
      selectin, VCAM-1, ICAM-1), chemokines (CXCL1, CXCL8, CXCL10, CCL2, CCL5), GM-CSF,
      iNOS and COX-2 in comparison to TNFalpha-stimulation. IFNgamma strongly induced
      PMN and PBMC adhesion on BUVEC involving CD4(+), CD8(+) and gammadelta-TCR(+)
      (WC1(+)) lymphocytes. Furthermore, IFNgamma-stimulation led to a strong
      upregulation in the transcription of VCAM-1, ICAM-1, CXCL10 and CCL2 genes and to
      a low to moderate increase in the E- and P-selectin, CXCL1, CXCL8, CCL5, COX-2
      and iNOS gene transcripts, but failed to enhance GM-CSF gene transcription. These
      results indicate that IFNgamma can be considered an important activator of
      endothelial cells in the bovine system, most probably by influencing the outcome
      of inflammatory responses through selective upregulation of immunoregulatory
      molecules.

PMID- 17516143
TI  - The effects of tetrahydrocurcumin and green tea polyphenol on the survival of
      male C57BL/6 mice.
AB  - The effect of feeding of two different antioxidants, tetrahydrocurcumin (TC) and
      green tea polyphenols (PPs) on the survival of male C57BL/6 mice was examined.
      Mice that started to receive diets containing TC (0.2%) at the age of 13 months
      had significantly longer average life spans (days, mean +/- SD) than control mice
      (797.6 +/- 151.2 vs.882 +/- 154.6, both n = 50, controls vs. TC treated, plus
      11.7%, P < 0.01). The 10% longest survival was also significantly greater in TC
      treated mice (plus 6.5%, P < 0.01). In contrast, in mice that started to receive
      TC in their 19th month of life, no significant difference from the control mice
      was found for either the average life span or the 10% longest survival. In mice
      that received water containing PPs (80 mg/l), the average life span was also
      significantly longer than in the control mice (801 +/- 121.5 vs. 852.7 +/- 88.2,
      plus 6.4%, P < 0.05), although the 10% longest survival was not significantly
      different from that in the control mice (P > 0.05). The body weights of the TC
      (but not PP) fed mice, were slightly (2-4%) but significantly (P < 0.05) lower
      than the values for the corresponding ages in the control mice in the first six
      months of treatment. Thereafter, the difference in average body weight between
      the control and the TC-fed animals was totally lost. Although an additional
      contribution of an unintended slight decrease in food intake due to TC feeding
      (suspected due to the difference in body weight) is not excluded, we suggest that
      the feeding of nutritional antioxidants such as TC and PPs may have the potential
      to beneficially modify the life spans of animals.

PMID- 17516144
TI  - The PsbZ subunit of Photosystem II in Synechocystis sp. PCC 6803 modulates
      electron flow through the photosynthetic electron transfer chain.
AB  - The psbZ gene of Synechocystis sp. PCC 6803 encodes the approximately 6.6 kDa
      photosystem II (PSII) subunit. We here report biophysical, biochemical and in
      vivo characterization of Synechocystis sp. PCC 6803 mutants lacking psbZ. We show
      that these mutants are able to perform wild-type levels of light-harvesting,
      energy transfer, PSII oxygen evolution, state transitions and non-photochemical
      quenching (NPQ) under standard growth conditions. The mutants grow
      photoautotrophically; however, their growth rate is clearly retarded under low
      light conditions and they are not capable of photomixotrophic growth. Further
      differences exist in the electron transfer properties between the mutants and
      wild type. In the absence of PsbZ, electron flow potentially increased through
      photosystem I (PSI) without a change in the maximum electron transfer capacity of
      PSII. Further, rereduction of P700(+) is much faster, suggesting faster cyclic
      electron flow around PSI. This implies a role for PsbZ in the regulation of
      electron transfer, with implication for photoprotection.

PMID- 17516145
TI  - The PsbP-like protein (sll1418) of Synechocystis sp. PCC 6803 stabilises the
      donor side of Photosystem II.
AB  - The PsbP-like protein of the cyanobacterium Synechocystis sp. PCC 6803 is a
      peripheral component of Photosystem II, located at the lumenal side of the
      thylakoid membrane. Removal of this protein leads to decreased competitive
      potential of a PsbP-like deletion mutant when grown in a mixture with wild-type
      cells. Flash-induced oxygen evolution traces of the mutant show a higher
      probability of misses, correlated with increased amplitudes of the S-states decay
      in the dark. Thermoluminescence emission traces demonstrate a changed charge
      recombination pattern in the mutant, the S(3)Q(B)(-) couple becoming the major
      species instead of the S(2)Q(B)(-). Our data suggest a possible role of the PsbP
      like protein in stabilisation of the charge separation in Photosystem II of
      cyanobacteria through interaction with the Mn cluster.

PMID- 17516146
TI  - Factor XIII gene V34L mutation in the Lebanese population: another unique feature
      in this community?
AB  - We studied the distribution of the Factor XIII gene V34L polymorphism in a sample
      of healthy Lebanese individuals to assess its prevalence and compare it with
      other populations. Factor XIII genotypes were determined using the Cardiovascular
      Disease (CVD) StripAssay (ViennaLab, Austria), which is based on a Polymerase
      Chain Reaction-Reverse hybridization technique. DNA from 205 unrelated healthy
      donors from our HLA database was used. The prevalence of Wild type, heterozygous,
      and homozygous genotypes was found to be 74.2%, 22.4%, and 3.4% respectively. The
      sampled Lebanese population showed that the prevalence of V34L carriers (25.8%)
      was lower than Caucasians in general (44.3%) and, interestingly, with a low
      allele frequency of 0.14 similar to that in Blacks and South Asians. This first
      report from Lebanon sheds light on an additional unique genetic feature of this
      population and will prospectively serve as a baseline statistical data for future
      investigations of the prevalence of Factor XIII V34L mutation in association with
      various clinical entities notably cardiovascular diseases.

PMID- 17516147
TI  - The significance of the concept of disease for justice in health care.
AB  - In this paper, I want to scrutinise the value of utilising the concept of disease
      for a theory of distributive justice in health care. Although many people believe
      that the presence of a disease-related condition is a prerequisite of a justified
      claim on health care resources, the impact of the philosophical debate on the
      concept of disease is still relatively minor. This is surprising, because how we
      conceive of disease determines the amount of justified claims on health care
      resources. Therefore, the severity of scarcity depends on our interpretation of
      the concept of disease. I want to defend a specific combination of a theory of
      disease with a theory of distributive justice. A naturalist account of disease,
      together with sufficientarianism, is able to perform a gate-keeping function
      regarding entitlements to medical treatment. Although this combination cannot
      solve all problems of justice in health care, it may inform rationing decisions
      as well.

PMID- 17516148
TI  - Seeking perfection: a Kantian look at human genetic engineering.
AB  - It is tempting to argue that Kantian moral philosophy justifies prohibiting both
      human germ-line genetic engineering and non-therapeutic genetic engineering
      because they fail to respect human dignity. There are, however, good reasons for
      resisting this temptation. In fact, Kant's moral philosophy provides reasons that
      support genetic engineering-even germ-line and non-therapeutic. This is true of
      Kant's imperfect duties to seek one's own perfection and the happiness of others.
      It is also true of the categorical imperative. Kant's moral philosophy does,
      however, provide limits to justifiable genetic engineering.

PMID- 17516149
TI  - Maximizing the value of validation findings to better understand treatment
      satisfaction issues for diabetes.
AB  - BACKGROUND: Variables associated with treatment satisfaction (TS) can be broadly
      categorized as precursors, ongoing treatment issues, and treatment outcomes. This
      study continues the validation process for the Insulin Treatment Satisfaction
      Questionnaire (ITSQ) while examining relationships between TS and these broader
      influences. METHODS: Data (N = 299) were collected in a RCT comparing safety and
      efficacy of inhaled vs. injectable insulin. Validation examined item and factor
      characteristics, reliability and validity. Regression analyses examined
      relationships between overall and domain specific TS and the broader influences.
      RESULTS: Patients with less previous or current treatment burden had greater TS
      (p < 0.001). Gender, injection fear, functioning, age, compliance and glycemic
      control were differentially related to TS at the beginning and end of study.
      Baseline satisfaction was predictive of future TS (p < 0.001). When all
      significant factors were examined together, lower burden with the current
      treatment and higher satisfaction with previous treatment continued to be key (p
      < 0.001) while other factors were no longer significant. Validation findings
      confirmed the ITSQ was psychometrically sound. CONCLUSION: Over the course of
      treatment, some factors are associated with TS at treatment start while others
      are key drivers at treatment end. This suggests that TS is not a static concept.

PMID- 17516150
TI  - Basis for a functional capacity evaluation methodology for patients with work
      related neck disorders.
AB  - BACKGROUND: Neck pain is a common musculoskeletal complaint and a relationship
      with reduced work-related functional capacity is assumed. A validated instrument
      to test functional capacity of patients with neck pain is unavailable. The
      objective of this study was to develop a Functional Capacity Evaluation (FCE),
      which is content valid for determining functional capacity in patients with work
      related neck disorders (WRND). METHODS: A review of epidemiological review
      literature was conducted to identify physical risk factors for WRND. RESULTS:
      Evidence was found that physical risk factors contribute in development of WRND.
      Physical risk factors were related to repetitive movements, forceful movements,
      awkward positions and static contractions of the neck or the neck/shoulder
      region. An FCE was designed based on the risk factors identified. Eight tests
      were selected to cover all risk factors: repetitive side reaching, repetitive
      reaching overhead, static overhead work, front carry, forward static bend neck,
      overhead lift and the neck strength test. Content validity of this FCE was
      established by providing the rationale, specific objectives and operational
      definitions of the FCE. CONCLUSIONS: Further research is needed to establish
      reliability and other aspects of validity of the neck-FCE.

PMID- 17516151
TI  - Pharmacodynamic model of interleukin-21 effects on red blood cells in cynomolgus
      monkeys.
AB  - Interleukin-21 (IL-21) is a novel cytokine that is currently under clinical
      investigations as a potential anti-cancer agent. Like many other anti-cancer
      agents, including other interleukins, IL-21 is seen to produce a broad range of
      biological effects that may be related to both efficacy and safety of treatment.
      The present analysis investigates the observed pharmacodynamics effects on red
      blood cells following various treatment schedules of human IL-21 administrated to
      cynomolgus monkeys. These effects are described by a novel non-linear mixed
      effects model that enabled separation of drug effects and sampling effects, the
      latter believed to be due partly to blood loss and partly to stress induced
      haemolysis in connection with blood sampling. Two different studies with a total
      of 9 different treatment groups of cynomolgus monkeys were used for model
      development. In conclusion, the model describes the IL-21 induced drop in red
      blood cells to be (1) caused by removal rather than suppression of production,
      consistent with increased reticulocyte concentration, and (2) considerably
      delayed compared to dosing, i.e. not related to the drop in red blood cells
      observed immediately post dose. It is believed that the structural model
      presented here can be used for other types of drug induced loss of red blood
      cells, whereas the mechanism for sampling related blood loss is relevant for
      investigations of anaemia in all pharmacological studies with smaller animals.

PMID- 17516152
TI  - The lasso--a novel method for predictive covariate model building in nonlinear
      mixed effects models.
AB  - Covariate models for population pharmacokinetics and pharmacodynamics are often
      built with a stepwise covariate modelling procedure (SCM). When analysing a small
      dataset this method may produce a covariate model that suffers from selection
      bias and poor predictive performance. The lasso is a method suggested to remedy
      these problems. It may also be faster than SCM and provide a validation of the
      covariate model. The aim of this study was to implement the lasso for covariate
      selection within NONMEM and to compare this method to SCM. In the lasso all
      covariates must be standardised to have zero mean and standard deviation one.
      Subsequently, the model containing all potential covariate-parameter relations is
      fitted with a restriction: the sum of the absolute covariate coefficients must be
      smaller than a value, t. The restriction will force some coefficients towards
      zero while the others are estimated with shrinkage. This means in practice that
      when fitting the model the covariate relations are tested for inclusion at the
      same time as the included relations are estimated. For a given SCM analysis, the
      model size depends on the P-value required for selection. In the lasso the model
      size instead depends on the value of t which can be estimated using cross
      validation. The lasso was implemented as an automated tool using PsN. The method
      was compared to SCM in 16 scenarios with different dataset sizes, number of
      investigated covariates and starting models for the covariate analysis. Hundred
      replicate datasets were created by resampling from a PK-dataset consisting of 721
      stroke patients. The two methods were compared primarily on the ability to
      predict external data, estimate their own predictive performance (external
      validation), and on the computer run-time. In all 16 scenarios the lasso
      predicted external data better than SCM with any of the studied P-values (5%, 1%
      and 0.1%), but the benefit was negligible for large datasets. The lasso cross
      validation provided a precise and nearly unbiased estimate of the actual
      prediction error. On a single processor, the lasso was faster than SCM. Further,
      the lasso could run completely in parallel whereas SCM must run in steps. In
      conclusion, the lasso is superior to SCM in obtaining a predictive covariate
      model on a small dataset or on small subgroups (e.g. rare genotype). Run in
      parallel the lasso could be much faster than SCM. Using cross-validation, the
      lasso provides a validation of the covariate model and does not require the user
      to specify a P-value for selection.

PMID- 17516153
TI  - Pharmacodynamic analysis of time-variant cellular disposition: reticulocyte
      disposition changes in phlebotomized sheep.
AB  - Most pharmacodynamic (PD) models of cellular response assume a time-invariant
      (i.e., constant) cellular disposition despite known changes in the disposition
      with time, such as the reticulocyte residence time in the systemic circulation
      during stress erythropoiesis. To account for changes in cellular disposition, a
      comprehensive PD model that involves endogenous erythropoietin (Epo),
      reticulocytes, and hemoglobin responses was developed in phlebotomized sheep that
      considers a time-variant reticulocyte residence time and allows for the
      simultaneous determination of changes in the cellular disposition and cellular
      production. Five sheep were phlebotomized to hemoglobin concentrations of
      approximately 4 g/dl. Epo concentrations, reticulocytes, and hemoglobin
      concentrations were frequently sampled for 5-7 days prior to and 25-30 days
      following the phlebotomy. Initial steady-state conditions were assumed and the
      time-variant reticulocyte residence time in the systemic circulation was
      semiparametrically represented using a constrained spline function. Hemoglobin
      production was modeled using a Hill function via an effect site compartment. The
      initial steady state reticulocyte residence time in the systemic circulation was
      estimated as 0.477 (0.100) (mean (SD)) days, which maximally increased 2.01- to
      2.64-fold higher than the initial steady-state residence time 5.95 (0.899) days
      post-phlebotomy (P < 0.01). On average, the residence time returned to steady
      state values 15.4 (2.36) days post-phlebotomy, which was not significantly
      different from the initial steady-state value (P > 0.05). The baseline hemoglobin
      production rate was estimated at 0.0929 (0.0472) g/kg/day and the maximum
      production rate under stress phlebotomy was estimated at 0.504 (0.0422) g/kg/day.
      These data indicate that endogenously released Epo under acute anemic conditions
      can increase hemoglobin production approximately 5-fold. The determined increase
      in reticulocyte residence time produced under stress erythropoiesis is similar to
      the commonly reported 2- to 3-fold increase observed in human patients.

PMID- 17516154
TI  - Involvement of MCP-1 in tubulointerstitial fibrosis through massive proteinuria
      in anti-GBM nephritis induced in WKY rats.
AB  - We investigated participation of monocyte chemoattractant protein-1 (MCP-1) in
      tubulointerstitial fibrosis and correlation between MCP-1 and proteinuria in
      Wistar-Kyoto (WKY) rats with glomerulonephritis induced by anti-glomerular
      basement membrane (anti-GBM) antibody. WKY rats showed marked proteinuria and
      severe glomerular crescent formation at 7 days post antibody injection. At 28
      days, tubulointerstitial fibrotic lesions were observed, followed by sustained
      heavy proteinuria and severe tubulointerstitial fibrosis at 56 days. Histological
      examination revealed that the overlapped immunoreactivities of MCP-1, rat
      albumin, and p65NF-kappaB were detected in the same tubular segments of nephritic
      kidney, and a significant positive correlation was observed between proteinuria
      and MCP-1 expression in the tubulointerstitial fibrosis. ED-1- and CD8-positive
      cells were also abundant, and there was a good correlation between
      monocyte/macrophage recruitment and MCP-1 expression in the tubulointerstitial
      area. These results suggest that MCP-1 participates in the progression of
      tubulointerstitial fibrosis, through massive albuminuria, which is accompanied by
      marked monocyte/macrophage recruitment.

PMID- 17516155
TI  - Transition of a compact intermediate state of pea lectin under the influence of
      different molecular weight polyethylene glycols.
AB  - The compact intermediate of the pea lectin found to exist at pH 2.4 was treated
      with low (PEG-400), medium (PEG-4000) and high (PEG-20,000) molecular weight
      PEGs. The changes occurring in the secondary structure of the protein were
      monitored by CD spectropolarimetry in the far-UV range, intrinsic fluorescence
      was used as a probe to observe the changes in the tertiary structure which is
      reflected by the changes in the tryptophan environment, further ANS binding
      studies were made to know the extent of exposure of the hydrophobic patches which
      is again indicative of the overall changes occurring in the tertiary structure of
      the protein. It was found that the three PEGs altered the secondary as well as
      tertiary structure of the pH 2.4 intermediate leading to the formation of three
      different intermediates. The intermediates were found to have non-native
      secondary structure as well as non-native tertiary structure. The intermediate
      formed by the action of PEG-400 was due to the induction of secondary and
      tertiary structure while the intermediates formed under the influence of PEG-4000
      and PEG-20,000 were due to loss in secondary structure and rearrangement in
      tertiary structure. Also the ANS binding studies showed the absence of any MG or
      MG-like structures formed in the folding /unfolding pathway induced by PEGs.

PMID- 17516156
TI  - Comparative evaluation of alpha-amylase refolding through two different
      artificial chaperone systems.
AB  - Two different artificial chaperone systems were evaluated in this work using
      either detergents or CDs as the stripping agents. Upon dilution of urea-denatured
      alpha-amylase to a non-denaturing urea concentration in the presence of the
      capturing agent, complexes of the detergent and non-native protein molecules are
      formed and thereby the formation of protein aggregates is prevented. The so
      called captured protein is unable to refold from the detergent-protein complex
      states unless a stripping agent is used to remove the detergent molecules. Our
      results by fluorescence, UV, turbidity measurement, circular dichroism, surface
      tension and activity assay indicated that the extent of refolding assistance was
      different due to different inter- and intra- molecular interactions in the two
      different systems. However, the high activity recovery in the presence of
      detergents, as the stripping agent, suggests that they can constitute suitable
      replacement for the more expensive and common stripping agent of cyclodextrins.

PMID- 17516157
TI  - Inhibition of CO(2) production from glucose by arginine in brain slices of rats.
AB  - In the present study we evaluated the in vivo effect of arginine on CO(2)
      production from glucose in a medium with physiological and high extracellular
      K(+) concentrations. We also tested the influence of the nitric oxide synthase
      inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), on the effects
      elicited by arginine in order to investigate the possible participation of NO
      and/or its derivatives on the effects of arginine on CO(2) production from
      glucose. Sixty-day-old rats were treated with a single intraperitoneal injection
      of saline (control; group I), arginine (0.8 g/kg; group II), L-NAME (2.0 mg/kg;
      group III) or arginine (0.8 g/kg) plus L-NAME (2.0 mg/kg; group IV) and were
      killed 1 h later. Results showed that arginine administration inhibited CO(2)
      production from glucose at physiological extracellular K(+) concentration and L
      NAME prevented such effect. In contrast, arginine administration had no effect on
      CO(2) production from glucose at high extracellular K(+) concentration. Based on
      these data, we also investigated the in vitro effect of arginine on CO(2)
      production from glucose in a medium with physiological extracellular K(+)
      concentration in hippocampus slices. Results showed that arginine (0.1-1.5 mM)
      when added to the incubation medium did not alter CO(2) production from glucose
      in hippocampus slices of untreated rats. In addition, we also demonstrated that
      arginine inhibits Na(+), K(+)-ATPase activity. The data indicate that the
      reduction of CO(2) production by arginine was probably mediated by NO and/or its
      derivatives, which could act inhibiting the activity of Na(+), K(+)-ATPase. The
      results suggest that arginine impairs energy metabolism in hippocampus slices of
      rats.

PMID- 17516158
TI  - Effect of T0901317 on hepatic proinflammatory gene expression in apoE-/- mice fed
      a high-fat/high-cholesterol diet.
AB  - OBJECTIVE: In present study, we employed cDNA-based microarray technique to
      investigate the effect of a synthetic LXR ligand T0901317 on hepatic gene
      expression of proinflammatory cytokines in apolipoprotein E knockout mice fed an
      atherogenic diet. METHODS AND RESULTS: Male 8-week-old apoE-/- mice were randomly
      divided into four groups, baseline group, vehicle group, prevention group and
      treatment group. All of the mice were fed a high-fat/high-cholesterol diet with
      or without LXR agonist T0901317 for 8 or 14 weeks. Gene array analysis found 17
      atherosclerosis-related genes with a 2- to 8-fold difference in expression level
      between vehicle-treated group and T0901317-treated group. It induced mRNA
      expression of proinflammatory cytokine tumor necrosis factor (TNF), but inhibited
      gene expression of several other proinflammatory cytokines including interleukin
      (IL)-1alpha, IL-6, and IL-7 in the liver. C-reactive protein, TNF, matrix
      metalloproteinase-9, IL-1alpha, IL-6, and IL-7 were verified by real-time
      quantitative PCR. Next, enzyme-linked immunosorbent assay analyses showed up
      regulation of TNFalpha levels and down-regulation of IL-alpha, IL-6, IL-7 levels
      in plasma sample. CONCLUSION: The synthetic LXR agonist T0901317 has paradoxical
      roles in hepatic gene expression of proinflammatory cytokines in apoE-/- mice.

PMID- 17516159
TI  - Transvenous bifocal left ventricular pacing after mechanical prosthetic tricuspid
      valve replacement with use of echocardiography to optimize pacing parameters.
AB  - A 56-year-old woman underwent placement of a permanent pacemaker to treat
      symptomatic bradycardia; she had a documented, severe atrioventricular (AV)
      conduction abnormality and was not taking any AV node-blocking drugs. She had a
      mechanical prosthetic valve in the tricuspid position, which had been implanted
      for severe valvular insufficiency caused by rheumatic heart disease. Pacing leads
      were successfully placed transvenously in the anterior cardiac and a
      posterolateral vein, which avoided the need for repeat thoracotomy.
      Echocardiographic and Doppler parameters were used to optimize interventricular
      as well as septal-to-lateral left ventricular (LV) time delay and reduce or avoid
      interventricular and LV mechanical dyssynchrony.

PMID- 17516160
TI  - Evaluation of left atrial and posterior mediastinal anatomy by multidetector
      helical computed tomography imaging: relevance to ablation.
AB  - INTRODUCTION: Increasing use of catheter ablation in the left atrium (LA)
      requires understanding of substrate anatomy, especially with regard to potential
      damage to adjacent structures. METHODS AND RESULTS: We reviewed multidetector
      helical computed tomography (MDCT) imaging on 42 subjects, 26 imaged before
      planned LA ablation for atrial fibrillation (AF), and 16 without AF. LA volume
      and dimensions were larger in patients with AF (p < 0.05) and the spine and aorta
      (Ao) impressed the LA more frequently in the AF group. The esophagus (Eo) was the
      predominant feature on the posterior LA wall, contacting it in all patients. The
      Ao was in contact with the LA body or the left inferior pulmonary vein (PV) in 32
      (76%) of 42 cases, and in 10 it ran along an indentation on the posterior aspect
      of the LA. The coronary sinus was adjacent to LA ablation sites, the azygos vein
      was rarely adjacent to those sites, and the left bronchus abutted the PV ostium
      but not the LA. Two patients had findings that directly impacted the ablation
      procedure: one patient had a dilated fluid filled Eo with esophageal stricture
      and underwent nasogastric decompression before ablation, and one was discovered
      to have an anomalous PV and underwent surgical repair. CONCLUSIONS: MDCT imaging
      identifies structures adjacent to the LA, which could be affected by ablation.
      Posterior LA topography can be influenced by the position of the Ao or by the
      proximity of the spine. Preprocedural imaging can characterize anatomic
      structures that could be vulnerable during ablation, and detect unusual pathology
      that can affect the treatment plan.

PMID- 17516161
TI  - Prevalence and molecular characterization of meq in feather follicular epithelial
      cells of Korean broiler chickens.
AB  - Marek's disease (MD) is a highly contagious lymphoproliferative disease of
      chickens. Meq is the relevant oncogene and four isoforms, long (L)-meq, meq,
      short (S)-meq and very short (VS)-meq, have been identified. Although MD is
      important in the poultry industry, the prevalence and molecular properties of
      Korean MD virus (MDV) among broiler chickens remain unclear. Therefore, we
      characterized meq in pooled feather tips sampled at 3- and 5-week-old chickens
      from 21 unvaccinated and 22 vaccinated broiler farms via nested-PCR and
      nucleotide sequence analysis. Multiple bands consisting of L-meq, meq, and S-meq
      amplicons were observed in a commercial vaccine (CVI988 + HVT), 1 (4.8%) and 5
      samples (22.7%) from unvaccinated and vaccinated farms, respectively. A strong
      meq amplicon was observed in a MD-related tumor tissue, 6 (28.6%) and 1 (4.5%)
      samples from unvaccinated and vaccinated farms, respectively. Six and one
      amplicons from unvaccinated (28.6%) and vaccinated farms (4.5%), respectively,
      were differentiated from CVI988 by nucleotide sequence analysis. Therefore, the
      relatively high rate of meq in the unvaccinated broiler farms constitutes support
      for vaccination. However, the existence of CVI988-related meq in unvaccinated
      chickens necessitates further study regarding the origins and pathoimmunological
      effects of the viruses on chickens.

PMID- 17516162
TI  - Neutral N-glycan patterns of the gastropods Limax maximus, Cepaea hortensis,
      Planorbarius corneus, Arianta arbustorum and Achatina fulica.
AB  - The N-glycosylation potentials of Limax maximus, Cepaea hortensis, Planorbarius
      corneus, Arianta arbustorum and Achatina fulica were analysed by investigation of
      the N-glycan structures of the skin and viscera glycoproteins by a combination of
      HPLC and mass-spectrometry methods. It is one of the first steps to enlarge the
      knowledge on the glycosylation abilities of gastropods, which may help to
      establish new cell culture systems, to uncover new means for pest control for
      some species, and to identify carbohydrate-epitopes which may be relevant for
      immune response. All snails analysed contained mainly oligomannosidic and small
      paucimannosidic structures, often terminated with 3-O-methylated mannoses. The
      truncated structures carried modifications by beta1-2-linked xylose to the beta
      mannose residue, and/or an alpha-fucosylation, mainly alpha1,6-linked to the
      innermost N-acetylglucosaminyl residue of the core. Many of these structures were
      missing the terminal N-acetylglucosamine, which has been shown to be a
      prerequisite for processing to complex N-glycans in the Golgi. In some species
      (Planorbarius corneus and Achatina fulica) traces of large structures, terminated
      by 3-O-methylated galactoses and carrying xylose and/or fucose residues, were
      also detected. In Planorbarius viscera low amounts of terminal alpha1-2
      fucosylation were determined. Combining these results, gastropods seem to be
      capable to produce all kinds of structures ranging from those typical in mammals
      through to structures similar to those found in plants, insects or nematodes. The
      detailed knowledge of this very complex glycosylation system of the gastropods
      will be a valuable tool to understand the principle rules of glycosylation in all
      organisms.

PMID- 17516163
TI  - Protection of the abnormal heart.
AB  - Myocardial ischemia and reperfusion injury have been extensively investigated in
      the laboratory mainly in healthy tissues. However, in clinical settings, ischemic
      heart disease coexists with certain illnesses, which could potentially influence
      the response of the myocardium to ischemia and reperfusion. Recent research has
      revealed that the abnormal heart may not be always vulnerable to ischemic injury.
      Furthermore, the effect of powerful means of protection, such as ischemic
      preconditioning, may not be in operation under certain pathological conditions.
      With this evidence in mind, the present review will focus on the response of the
      abnormal heart to ischemia and reperfusion, the possible underlying mechanisms,
      and potential cardioprotective strategies.

PMID- 17516164
TI  - Return to the fetal gene program protects the stressed heart: a strong
      hypothesis.
AB  - A common feature of the hemodynamically or metabolically stressed heart is the
      return to a pattern of fetal metabolism. A hallmark of fetal metabolism is the
      predominance of carbohydrates as substrates for energy provision in a relatively
      hypoxic environment. When the normal heart is exposed to an oxygen rich
      environment after birth, energy substrate metabolism is rapidly switched to
      oxidation of fatty acids. This switch goes along with the expression of "adult"
      isoforms of metabolic enzymes and other proteins. However, the heart retains the
      ability to return to the "fetal" gene program. Specifically, the fetal gene
      program is predominant in a variety of pathophysiologic conditions including
      hypoxia, ischemia, hypertrophy, and atrophy. A common feature of all of these
      conditions is extensive remodeling, a decrease in the rate of aerobic metabolism
      in the cardiomyocyte, and an increase in cardiac efficiency. The adaptation is
      associated with a whole program of cell survival under stress. The adaptive
      mechanisms are prominently developed in hibernating myocardium, but they are also
      a feature of the failing heart muscle. We propose that in failing heart muscle at
      a certain point the fetal gene program is no longer sufficient to support cardiac
      structure and function. The exact mechanisms underlying the transition from
      adaptation to cardiomyocyte dysfunction are still not completely understood.

PMID- 17516165
TI  - Connexin 43 in ischemic pre- and postconditioning.
AB  - Connexin 43 (Cx43) is the predominant protein forming gap junctions and non
      junctional hemichannels in ventricular myocardium, but Cx43 is also localized at
      the inner membrane of cardiomyocyte mitochondria. In cardiomyocytes, Cx43 is
      involved in the formation of reactive oxygen species, which are central to the
      signal transduction cascade of ischemic preconditioning's protection.
      Accordingly, genetically-induced or age-related loss of Cx43 abolishes infarct
      size reduction by ischemic preconditioning. Similarly, mitochondrial import
      inhibition of Cx43 completely blocks infarct size reduction by pharmacological
      preconditioning with diazoxide. In contrast to its importance for preconditioning
      induced cardioprotection, Cx43 is not important for infarct size reduction by
      ischemic postconditioning. In summary, Cx43--especially Cx43 localized in
      mitochondria--appears to be one key element of the signal transduction cascade of
      the protection by preconditioning.

PMID- 17516166
TI  - Cardioprotective actions of peptide hormones in myocardial ischemia.
AB  - The myocardium represents a major source of several families of peptide hormones
      under normal physiological conditions and the plasma concentrations of many of
      these "cardiac peptides" (or related pro-peptide fragments) are substantially
      augmented in many cardiac disease states. In addition to well-characterised
      endocrine functions of several of the cardiac peptides, pleiotropic functions
      within the myocardium and the coronary vasculature represent a significant aspect
      of their actions in health and disease. Here, we focus specifically on the
      cardioprotective roles of four major peptide families in myocardial ischemia and
      reperfusion: adrenomedullin, kinins, natriuretic peptides and the urocortins. The
      patterns of early release of all these peptides are consistent with roles as
      autacoid cardioprotective mediators. Clinical and experimental research indicates
      the early release and upregulation of many of these peptides by acute ischemia
      and there is a convincing body of evidence showing that exogenously administered
      adrenomedullin, bradykinin, ANP, BNP, CNP and urocortins are all markedly
      protective against experimental myocardial ischemia-reperfusion injury through a
      conserved series of cytoprotective signal transduction pathways. Intriguingly,
      all the peptides examined so far have the potential to salvage against infarction
      when administered specifically during early reperfusion. Thus, the myocardial
      secretion of peptide hormones likely represents an early protective response to
      ischemia. Further work is required to explore the potential therapeutic
      manipulation of these peptides in acute coronary syndromes and their promise as
      biomarkers of acute myocardial ischemia.

PMID- 17516167
TI  - Mitochondria and cardioprotection.
AB  - Major factors linking mitochondrial dysfunction with myocardial injury are
      analyzed along with protective mechanisms elicited by endogenous processes and
      pharmacological treatments. In particular, a reduced rate of ATP hydrolysis and a
      slight increase in ROS formation appear to represent the prevailing components of
      self-defense mechanisms, especially in the case of ischemic preconditioning.
      These protective processes are activated by signaling pathways, which converge on
      mitochondria activating the mitochondrial K(ATP) channels and/or inhibiting the
      mitochondrial permeability transition pore. These pathways can also be stimulated
      by pharmacological treatments. Another major goal for cardioprotection is
      decreasing the burst in mitochondrial ROS formation that characterizes post
      ischemic reperfusion. Finally, mitochondrial targets for therapeutic intervention
      may include the switch of substrate being utilized, because inhibition of fatty
      acid oxidation is associated with cardioprotective effects.

PMID- 17516168
TI  - Fibroblast growth factor-2 and cardioprotection.
AB  - Boosting myocardial resistance to acute as well as chronic ischemic damage would
      ameliorate the detrimental effects of numerous cardiac pathologies and reduce the
      probability of transition to heart failure. Experimental cardiology has pointed
      to ischemic and pharmacological pre- as well as post-conditioning as potent acute
      cardioprotective manipulations. Additional exciting experimental strategies
      include the induction of true regenerative and/or angiogenic responses to the
      damaged heart, resulting in sustained structural and functional beneficial
      effects. Fibroblast growth factor-2 (FGF-2), an endogenous multifunctional
      protein with strong affinity for the extracellular matrix and basal lamina and
      well-documented paracrine, autocrine and intracellular modes of action, has been
      shown over the years to exert acute and direct pro-survival effects,
      irrespectively of whether it is administered before, during or after an ischemic
      insult to the heart. FGF-2 is also a potent angiogenic protein and a crucial
      agent for the proliferation, expansion, and survival of several cell types
      including those with stem cell properties. Human clinical trials have pointed to
      a good safety record for this protein. In this review, we will present a case for
      the low molecular weight isoform of fibroblast growth factor-2 (lo-FGF-2) as a
      very promising therapeutic agent to achieve powerful acute as well as sustained
      benefits for the heart, due to its cytoprotective and regenerative properties.

PMID- 17516169
TI  - Signaling pathways in ischemic preconditioning.
AB  - Ischemic preconditioning renders the heart resistant to infarction from
      ischemia/reperfusion. Over the past two decades a great deal has been learned
      about preconditioning's mechanism. Adenosine, bradykinin, and opioids act in
      parallel to trigger the preconditioned state and do so by activating PKC. While
      adenosine couples directly to PKC through the phospholipases, bradykinin and
      opioids do so through a complex pathway that includes in order:
      phosphatidylinositol 3-kinase (PI3-kinase), Akt, nitric oxide synthase, guanylyl
      cyclase, PKG, opening of mitochondrial K(ATP) channels, and activation of PKC by
      redox signaling. There are even differences between the opioid and bradykinin
      coupling as the former activates PI3-kinase through transactivation of the
      epidermal growth factor receptor while the latter has an unknown coupling
      mechanism. Protection stems from inhibition of formation of mitochondrial
      permeability transition pores early in reperfusion through activation of the
      survival kinases, Akt and ERK. These kinases are activated as a result of PKC
      somehow promoting signaling from adenosine A(2) receptors early in reperfusion.
      The survival kinases are thought to inhibit pore formation by phosphorylating GSK
      3beta. The reperfused heart requires the support of the protective signals for
      only about an hour after which the ischemic injury is repaired and the signals
      are no longer needed.

PMID- 17516170
TI  - At the borders, on the edge: use of injected methamphetamine in Tijuana and
      Ciudad Juarez, Mexico.
AB  - Injection drug use is of increasing concern along the US-Mexico border where
      Tijuana and Ciudad (Cd.) Juarez are located. Methamphetamine has long been
      manufactured and trafficked through Mexico, with low rates of use within Mexico.
      With methamphetamine use now considered epidemic in the United States, and with
      associated individual and community harms such as HIV, STDs, domestic violence
      and crime, there is concern that rates of methamphetamine in the Northwestern
      border regions of Mexico may be rising. We conducted a qualitative study to
      explore the context of injection drug use in Tijuana and Cd. Juarez and included
      questions about methamphetamine. Guided in-depth interviews were conducted with
      10 male and 10 female injection drug users (IDUs) in Tijuana and 15 male and 8
      female IDUs in Cd. Juarez (total N = 43). Topics included types of drug used,
      injection settings, access to sterile needles and environmental influences.
      Interviews were taped, transcribed verbatim and translated. Content analysis was
      conducted to identify themes. The median age of injectors in both cities was 30.
      Methamphetamine was injected, either alone or in combination with other drugs by
      injectors in both Tijuana (85%) and Cd. Juarez (17%) in the 6 months previous to
      interview. Several important themes emerged with respect to methamphetamine use
      in both cities. IDUs in both cities considered methamphetamine to be widely used
      in Tijuana and infrequently used in Cd. Juarez, while the converse was true for
      cocaine. In both cities, stimulant (either cocaine or methamphetamine) use was
      widespread, with 85% in Tijuana and 83% in Cd. Juarez reporting current use of a
      stimulant, most often used in combination with heroin. Some injectors reported
      knowledge of local manufacturing and one had direct experience in making
      methamphetamine; some cross-border use and trafficking was reported. Injectors
      reported concerns or experience with serious health effects of methamphetamine
      such as abscesses or tuberculosis. Our study suggests that injected
      methamphetamine is entrenched in Tijuana and that Cd. Juarez may experience a
      methamphetamine outbreak in the future. Robust targeted interventions for both
      injected and non-injected methamphetamine should be a public health priority in
      both cities.

PMID- 17516171
TI  - Lectin-modified microchannels for mammalian cell capture and purification.
AB  - There is a need for cell purification strategies suitable for handling small cell
      populations (tens to thousands of cells). We present here a novel strategy for
      small scale cell purifications using lectin-modified microchannels. Mammalian
      cells can be selectively captured in lectin-modified channels and eluted with a
      solution of the lectin's inhibiting sugar. As a proof-of-principle demonstration,
      two cell lines with different binding affinities to the lectin Sambucus nigra
      agglutinin (SNA) were combined at various ratios and introduced into SNA-modified
      microchannels. After incubation and washing, enrichments of approximately ten
      fold were obtained for the SNA-binding cell type. The results demonstrate the
      potential of this miniaturized device for manipulation and purification of
      limited quantities of cells.

PMID- 17516172
TI  - An ultra-thin PDMS membrane as a bio/micro-nano interface: fabrication and
      characterization.
AB  - We report a method for making ultra-thin PDMS membrane devices. Freely suspended
      membranes as thin as 70 nm have been fabricated. Bulging tests were performed
      with a custom built fluidic cell to characterize large circular membranes. The
      fluidic cell allows the media (such as air or water) to wet one side of the
      membrane while maintaining the other side dry. Pressure was applied to the
      membrane via a liquid manometer through the fluidic cell. The resulting load
      deflection curves show membranes that are extremely flexible, and they can be
      reproducibly loaded and unloaded. Such devices may potentially be used as
      mechanical and chemical sensors, and as a bio-nano/micro interface to study
      cellular mechanics in both static and dynamic environments.

PMID- 17516173
TI  - Low noise bipolar photodiode array protein chip based on on-chip bioassay for the
      detection of E. coli O157:H7.
AB  - A bipolar photodiode array (PDA) protein chip is presented for the detection of
      E. coli O157:H7. Through unique design of the bipolar PDA microchip, the device
      was able to detect E. coli O157:H7 directly on the surface of the bipolar PDA.
      The bipolar PDA microchip maintained low noise level in the entire process of on
      chip protein assay and demonstrated high performance of analog signal processing.
      At every reaction step of the on-chip bioassay, stability of wet photodiode
      detection elements was confirmed by monitoring the variance of their photosignals
      with respect to the irradiated red beam. The background signal represented less
      than 1.8% variance with respect to maximum signal of photodiode detection
      elements. As a result of using the on-chip bioassay, any complicated optical
      alignment and components could be removed in the constructed protein chip. This
      protein chip enables direct optical detection of E. coli O157:H7 eliminating the
      need of conventional expensive microplate reader that is incompatible with size
      of sampling platform of protein chip. The independence of the constructed protein
      chip on conventional microplate reader can contribute greatly to further
      miniaturization of protein chip and field usable lab-on-a-chip.

PMID- 17516174
TI  - A microfabricated platform probing cytoskeleton dynamics using multidirectional
      topographical cues.
AB  - Cell migration, which involves complicated coordination of cytoskeleton elements
      and regulatory molecules, plays a central role in a large variety of biological
      processes from development, immune response to tissue regeneration. However,
      conventional methods to study in vitro cell migration are often limited to
      stimulating a cell along a single direction or at a single location. This
      restriction prevents a deeper understanding of the fundamental mechanisms that
      control the spatio-temporal dynamics of cytoskeleton. Here we report a novel
      microfabricated platform that enables a multi-directional stimulation to a cell
      using topographical cues. In this device, cells were seeded on a grid-patterned
      topographically structured surface composed of 2 microm wide and 2 microm high
      straight ridges. Because the size of a unit grid was smaller than a single cell,
      each cell was simultaneously experiencing contact guidance leading to different
      directions. The device showed that healthy cells preferred to align and migrate
      in the direction of the longer side of the grid. But cells with impaired
      intracelluar tension force generation exhibited multiple uncoordinated cell
      protrusions along guiding ridges in all directions. Our results demonstrate the
      importance of actomyosin network in long-range communication and regulation of
      local actin polymerization activities. This platform will find wide applications
      in investigations of signal transduction and regulation process in cell
      migration.

PMID- 17516175
TI  - Applying Taguchi methods for solvent-assisted PMMA bonding technique for static
      and dynamic micro-TAS devices.
AB  - This work examines numerous significant process parameters in the solvent
      assistant Polymethyl methacrylate (PMMA) bonding scheme and presents two Micro
      total-analysis System (micro-TAS) devices generated by adopting the optimal
      bonding parameters. The process parameters considered were heating temperature,
      applied loading, duration and solution. The effects of selected process
      parameters on bonding dimensions loss and strength, and subsequent optimal
      setting of the parameters were accomplished using Taguchi's scheme. Additionally,
      two micro-TAS devices were realized using a static paraffin microvalve and a
      dynamic diffuser micropump. The PMMA chips were carved using a CO2 laser that
      patterned device microchannels and microchambers. The operation principles,
      fabrication processes and experimental performance of the devices are discussed.
      This bonding technique has numerous benefits, including high bonding strength
      (240 kgf/cm2) and low dimension loss (2-6%). For comparison, this work also
      demonstrates that the normal stress of this technology is 2-15 times greater than
      that of other bonding technologies, including hot embossing, anodic bonding,
      direct bonding and thermal fusion bonding.

PMID- 17516176
TI  - A model for predicting magnetic particle capture in a microfluidic bioseparator.
AB  - A model is presented for predicting the capture of magnetic micro/nano-particles
      in a bioseparation microsystem. This bioseparator consists of an array of
      conductive elements embedded beneath a rectangular microfluidic channel. The
      magnetic particles are introduced into the microchannel in solution, and are
      attracted and held by the magnetic force produced by the energized elements.
      Analytical expressions are obtained for the dominant magnetic and fluidic forces
      on the particles as they move through the microchannel. These expressions are
      included in the equations of motion, which are solved numerically to predict
      particle trajectories and capture time. This model is well-suited for parametric
      analysis of particle capture taking into account variations in particle size,
      material properties, applied current, microchannel dimensions, fluid properties,
      and flow velocity.

PMID- 17516177
TI  - Reforming mental health care in Victoria: a decade later.
AB  - OBJECTIVE: From 1994, the Australian State of Victoria began a major
      transformation of its public mental health service system. In June 2006, St
      Vincent's Mental Health hosted a conference to reflect on the changes and
      identify steps to be taken over the next decade. METHOD: Participants came from
      Victoria's 21 adult mental health services, consumer and carer groups, and
      psychiatric disability rehabilitation and support organizations. They met in
      small groups, and discussed pre-set topics. Their observations were pooled in
      plenary sessions. RESULTS: Participants agreed the changes had had many positive
      outcomes. People most affected by mental illness had priority for treatment.
      Services were better structured to meet their needs, and staff were more familiar
      with community-based care. Negatives included restricted service access for some
      groups, insufficient resourcing to meet increased service demand and clinical
      staff not maintaining specialist skills. CONCLUSIONS: The conference enabled
      experiences to be shared and ideas exchanged about improvements.

PMID- 17516178
TI  - Service utilisation by rural residents with mental health problems.
AB  - OBJECTIVE: To examine the level and type of service utilisation by rural
      residents for mental health problems, and to explore the influence of level of
      need, sociodemographic factors and town size on such service use. METHOD: This
      was a cross-sectional, community-based study. Subjects were recruited from three
      locales in rural north-west Victoria: a large regional centre, towns of 5,000
      20,000 population and towns of <5,000 population. Three hundred and ninety-one
      individuals (54% females) participated. A logistic regression analysis was used
      to investigate which factors (i.e. need, sociodemographic and town size)
      predicted lifetime help-seeking for emotional or mental problems from formal
      health providers in the study sample. RESULTS: Factors that predicted having ever
      sought help from a formal health provider for emotional or mental health problems
      were: a lifetime and/or current psychiatric disorder, being female, being
      separated, divorced or widowed, and living in medium sized towns (population
      5,000-20,000). CONCLUSIONS: While traditionally known predictors of help-seeking,
      i.e need and gender, were associated with help seeking in this study, help
      seeking for mental health problems was also more common amongst individuals
      living in medium sized rural towns than those living in a large regional city.
      Possible explanations include availability, accessibility and organisation of
      services, and individual and/or community attitudes towards help seeking.

PMID- 17516179
TI  - Involving carers in mental health service development.
AB  - OBJECTIVE: A project designed to enhance carer participation in a mental health
      service is described. METHOD: Carers of people with a mental illness were
      involved in reviewing and developing policies, and developing a carer rights and
      responsibilities booklet. RESULTS: Policies relevant to carers of people with a
      mental illness were reviewed and updated, and new policies developed to cover
      existing gaps. Carer and staff awareness of policies was increased. A carer
      rights and responsibilities booklet was developed. CONCLUSIONS: Involving carers
      at this level of service development enhances carer awareness and understanding
      of the processes involved in a mental health service, and improves staff
      understanding of carer issues and viewpoints. This process is valuable for mental
      health services, resulting in positive outcomes.

PMID- 17516180
TI  - Stigma and quality of life as experienced by people with mental illness.
AB  - OBJECTIVES: The aim of this study was to assess the extent to which people with
      mental illness in a New Zealand setting encounter stigma and discrimination and
      to examine their satisfaction with quality of life. METHOD: Patients under the
      care of a range of community mental health services were invited to participate
      in a survey. Fifty-three females and 47 males completed questionnaires concerning
      stigma, discrimination and quality of life. Demographic and diagnostic
      characteristics were also recorded. RESULTS: The majority of participants
      reported experiencing stigma and discrimination in a variety of contexts. In
      association with this, they had experienced dissatisfaction with their quality of
      life in a number of areas. CONCLUSIONS: The experience of stigma and
      dissatisfaction with quality of life among people with mental illness is common.
      This has implications for clinical assessment and management.

PMID- 17516181
TI  - Overview of psychiatric ethics I: Professional ethics and psychiatry.
AB  - OBJECTIVE: The aim of this paper is to describe the current status of psychiatric
      ethics as a form of professional ethics and apply this approach to a common
      clinical situation. CONCLUSION: Psychiatry is a profession and, like all
      professions, comprises a set of specific skills and knowledge that are applied
      for the 'common good' of society. Such a proposition places the psychiatrist in a
      position of tension between contractarian and Hippocratic ideals of ethical
      conduct, in that there is an assumption of moral equivalence between the law and
      ethics. The supposition that legally defensible behaviours are the same as
      ethically defensible behaviours is integral to the definition of professional
      ethics. This frequently places psychiatrists at odds with the 'do no harm'
      principle.

PMID- 17516182
TI  - Overview of psychiatric ethics II: Virtue ethics and the ethics of care.
AB  - OBJECTIVE: The aim of this paper is to consider the components of two moral
      theories--the ethics of virtue and the ethics of care--and their relationship to
      psychiatry. CONCLUSIONS: Although both theories reflect fundamentally desirable
      human qualities, neither provides a comprehensive account of psychiatric ethics.
      We are therefore drawn to a similar conclusion as those of Hare (1993) and Bloch
      and Green (2006), in that these theories offer a complementary approach to other
      ethical theories in psychiatry.

PMID- 17516183
TI  - Fitness issues in the context of judicial proceedings.
AB  - OBJECTIVE: This paper provides a conceptual, historical and legislative overview
      of fitness issues. These include fitness to be interrogated or charged, to plead,
      to be tried and to be sentenced in the context of Australia and New Zealand.
      CONCLUSIONS: Legislation regarding fitness issues needs to strike a balance
      between protecting the rights of mentally impaired defendants to a fair trial
      process and recognizing that mental illness in itself does not absolutely
      preclude participation in a trial process or necessarily diminish criminal
      responsibility. Although the key determinants of fitness seem to be the ability
      to cope with court processes and communicate with counsel, the application of
      clinical judgement to legal criteria is not always straightforward.

PMID- 17516184
TI  - Searching the Silver trail: Charles van Onselen, Joe Silver and Jack the Ripper.
AB  - OBJECTIVE: South African historian Charles van Onselen's discovery of the
      identity of Jack the Ripper is described. The author was consulted by van Onselen
      during the writing of the latter's book, "The Fox and the Flies: Joe Silver,
      Racketeer and Psychopath", which suggested the identity of Jack the Ripper and
      was first published earlier this year. CONCLUSIONS: van Onselen's investigations
      into the life of Joe Silver, a Polish Jewish brothel owner in the early days of
      Johannesburg, revealed an extraordinary criminal career starting in London and
      covering the Atlantic zone before ending on the Eastern front during World War I,
      where he was executed by the Austrians. Research over decades showed that Silver
      fitted the profile of The Ripper and spent the rest of his life trying to cover
      his trail to avoid detection. Having contracted syphilis, he bore an extreme
      hatred towards women and initiated the Autumn of Terror in a catathymic crisis
      when his daughter was born. Driven by obsessive ambivalence towards his mother,
      at the end of his life he made a final doomed attempt to achieve some kind of
      union with her.

PMID- 17516185
TI  - Component analysis of dialectical behavior therapy skills training.
AB  - OBJECTIVE: This paper aims to examine patient perceptions of the relative
      effectiveness of components of dialectical behavior therapy group skills
      training. METHOD: Nineteen patients rated their perceptions of the relative
      effectiveness of 27 separate dialectical behavior therapy skills after completing
      6 months standard dialectical behavior therapy. Two-tailed t-tests were used,
      comparing the first ranked skill with all other skills. RESULTS: The 27 skills
      were ranked by means in order of perceived value. Eleven skills were
      statistically significantly different from the first ranked skill. CONCLUSIONS:
      The data in this pilot study contributes in a small way to dialectical behavior
      therapy dismantling research and warrants a larger multi-centred study. A planned
      future study will compare patient rankings of skills with clinical outcomes.

PMID- 17516186
TI  - Public sector group treatment for severe personality disorder: a 12-month follow
      up study.
AB  - OBJECTIVE: The results of an evaluation of an innovative pubic sector treatment
      program for patients with borderline personality disorder (BPD) with a history of
      unsuccessful treatment attempts and severe self-harm are presented. METHOD: DSM
      IV axis I and axis II diagnoses, psychiatric symptoms, patterns of self-harm,
      suicidality, coping styles, and quality of life were assessed for 27 women who
      completed a 6-month residential program. Pre- and post-treatment assessments and
      a 12-month follow-up were undertaken. RESULTS: At 12-month follow-up,
      significantly fewer participants met criteria for BPD. Significant post-treatment
      gains, including reduced levels of depression, anxiety and hopelessness, and
      improvements in some coping style and quality of life domains, were maintained at
      follow-up. The results in relation to self-harm indicated considerable within
      sample variability. CONCLUSION: Findings indicating clinically significant
      improvements in psychiatric symptoms and coping, along with mixed results in
      relation to self-harm and quality of life, are encouraging for the continued
      development of treatment services for this challenging patient group.

PMID- 17516187
TI  - Mentoring young researchers: can the Donald J Cohen Fellowships model be
      applicable and useful to Australasian psychiatry?
AB  - OBJECTIVES: To describe the experience with the Donald J Cohen Fellowship program
      of the International Association for Child and Adolescent Psychiatry and Allied
      Professions (IACAPAP) and examine whether this model may be applied by the RANZCP
      to attract and support young researchers in Australasia. METHODS: The program at
      the September 2006 IACAPAP conference included 50 young researchers, 16 mentors
      and 8 'host fellows', and consisted of exclusive poster sessions, daily small
      group mentoring meetings, oral presentation of selected papers, and a summary and
      feedback session. RESULTS: Informal feedback from mentors, mentees and conference
      organisers was very positive. CONCLUSIONS: A proposal about funding, participants
      and activities is presented. This suggests that a mentoring model similar to the
      Donald J Cohen Fellowship program can be easily conducted in Australasia.
      Implementing a program of this type would give College Fellows, the Australian
      Medical Council, the Commonwealth Government and other relevant organizations a
      clear message that the RANZCP is seriously committed to fostering and supporting
      research.

PMID- 17516188
TI  - Consumer participation in mental health research: articulating a model to guide
      practice.
AB  - OBJECTIVE: Consumer involvement in mental health research is considered both a
      right and a benefit, despite the identified barriers to forming effective
      collaborative relationships. The purpose of this paper is to examine the
      literature relating to consumer involvement in mental health research with a view
      to articulating a model to guide this process. METHOD: A qualitative review of
      the relevant literature was undertaken. Literature referring to consumer roles in
      research was accessed and reviewed with the aim of articulating the benefits of,
      and barriers to, consumer participation in research. RESULTS: The literature has
      identified a number of important benefits and some significant barriers to
      consumer involvement in mental health research. However, a clear model to
      articulate definitions of involvement is lacking. Four distinct levels of
      involvement were articulated. CONCLUSIONS: The identification of clearly defined
      models for consumer involvement in mental health research is important in order
      to facilitate collaboration and avoid tokenism. Research is required in order to
      determine the applicability of these models within actual research projects.

PMID- 17516189
TI  - Prolonged anticholinergic delirium following antihistamine overdose.
AB  - OBJECTIVE: A case of anticholinergic delirium in a female adolescent is
      described, exploring the pharmacokinetic reasons for the prolonged time course
      and reviewing the management provided. CONCLUSION: A 14 year old female
      hospitalised for depression ingested large quantities of promethazine and
      cyproheptadine. A severe anticholinergic delirium ensued which resolved after six
      days, much longer than the expected duration. The likely cause of the prolonged
      delirium was the interaction of promethazine and fluvoxamine through the
      inhibition of the CYP2D6 enzyme. The patient's young age, the severity of the
      poisoning and the use of drugs with anticholinergic properties to manage the
      delirium may also have contributed. The delirium may have been reversed had a
      cholinesterase inhibitor been provided soon after the overdose.

PMID- 17516191
TI  - Should psychiatric facilities be smoke free, and are we even asking the right
      questions?

PMID- 17516192
TI  - Suicide for scrutinizers.

PMID- 17516193
TI  - Combination antidepressants are not yet proven therapy in the treatment of
      depression.

PMID- 17516196
TI  - Under the Rainbow Tree: Professor Robert Barrett's legacy to the RANZCP College
      examinations.

PMID- 17516203
TI  - Do we already understand all aspects connecting clearance and autoimmunity?

PMID- 17516204
TI  - Inflammatory clearance of apoptotic cells after UVB challenge.
AB  - In the human body, every day billions of apoptotic cells are produced. Removal of
      these cells is necessary, to prevent the release of intracellular toxic
      constituents, and occurs very effectively via phagocytosis by (semi)-professional
      phagocytes. This elimination process occurs rapidly and without inflammation. In
      systemic lupus erythematosus (SLE) a disturbed elimination of apoptotic cells has
      been implicated in the induction and reactivation of the disease. Accumulation of
      apoptotic cells may result in autoantibody formation. A delayed, pro-inflammatory
      clearance is also thought to play a crucial role in the development of
      inflammatory lesions once the disease has manifested. One of the hallmarks of
      patients with SLE is the development of cutaneous lesions upon exposure to
      sunlight. In this review, we will focus on apoptotic cells, their elimination,
      and the consequences of a disturbed elimination of apoptotic cells on the
      development of UVB induced inflammatory skin lesions.

PMID- 17516205
TI  - Search for novel cell surface markers of apoptotic cells.
AB  - Surface markers of apoptotic cells are of great interest as potential targets for
      non-destructive detection and study of these cells. They are also important for
      apoptotic cell recognition and subsequent clearance by cells of the immune
      system. Recently, it was found that apoptosis is accompanied by not only the loss
      of plasma membrane asymmetry detected by Annexin V, but also by changes in cell
      surface glycoconjugates. These novel markers of apoptosis are alpha-D-mannose and
      beta-D-galactose-specific plasma membrane glycoproteins whose expression is
      substantially increased after induction of apoptosis. The glyconeoepitopes
      described in this article are proposed to be useful for both, the detection of
      apoptotic cells and the isolation of the latter, from mixed populations.

PMID- 17516206
TI  - Modulation of the immune system by dying cells and the phosphatidylserine-ligand
      annexin A5.
AB  - Apoptotic cell death and the efficient clearance of dying cells are essential
      mechanisms to control tissue homeostasis and to eliminate potential autoantigens.
      Numerous alterations on the surfaces of dying cells define a highly
      characteristic membrane signature and enable an unequivocal distinction from
      vital cells. This way, phagocytosis is initiated and signalling events induced
      which minimize inflammatory reactions. Therefore, the use of proteins interfering
      with the clearance process may open up new vistas to improve immunization
      strategies and may help to understand the mechanisms of autoimmune diseases.

PMID- 17516207
TI  - Contribution of histidine-rich glycoprotein in clearance of immune complexes and
      apoptotic cells: implications for ameliorating autoimmune diseases.
AB  - The molecular mechanisms that protect against the harmful properties of immune
      complexes and dying cells are not well understood. This review focuses on newly
      discovered mechanisms for the disposal of immune complexes and apoptotic cells by
      histidine-rich glycoprotein (HRG). Since HRG is abundantly synthesized by the
      liver and released into the blood stream at basal levels, it is readily available
      to engage in the removal of circulating modified self (e.g. apoptotic cells) and
      non-self (e.g. immune complexes) antigens, whereas other known mechanisms, such
      as the complement system, require pre-activation and are often accompanied by
      phlogistic events. These findings suggest clearance mechanism hierarchies.
      Through its interactions with naked DNA and immune complexes, HRG may mask
      epitopes recognized by autoantibody-producing B cells (e.g. rheumatoid factors
      and anti-double stranded DNA antibodies). The latter property may regulate
      adaptive immune system activation and has important implications for the
      involvement of HRG in ameliorating autoimmune reactions. Properties of HRG and
      possible protective actions of HRG-dependent clearance mechanisms are discussed.

PMID- 17516208
TI  - Clearance of dying cells and autoimmunity.
AB  - Phagocytic clearance of apoptotic cells is an important physiologic homeostatic
      mechanism that is associated with non-inflammatory or anti-inflammatory sequalae.
      Disruption of the process of apoptotic cell clearance may contribute to
      development of a number of inflammatory and autoimmune diseases. In this review,
      we summarize the molecular pathways that have been suggested to account for
      phagocytic clearance of apoptotic cells. We discuss potential mechanisms for
      regulation of phagocytosis and the implications for development of autoimmunity.

PMID- 17516209
TI  - The affirmative response of the innate immune system to apoptotic cells.
AB  - Growing evidence exists for a new role for apoptotic cell recognition and
      clearance in immune homeostasis. Apoptotic cells at all stages, irrespective of
      membrane integrity, elicit a signature set of signaling events in responding
      phagocytes, both professional and non-professional. These signaling events are
      initiated by receptor-mediated recognition of apoptotic determinants,
      independently of species, cell type, or apoptotic stimulus. We propose that the
      ability of phagocytes to respond to apoptotic targets with a characteristic set
      of signaling events comprises a second distinct dimension of innate immunity, as
      opposed to the traditional innate discrimination of self vs. non-self. We further
      propose that a loss or abnormality of the signaling events elicited by apoptotic
      cells, as distinct from the actual clearance of those cells, may predispose to
      autoimmunity.

PMID- 17516210
TI  - The origin of extracellular DNA during the clearance of dead and dying cells.
AB  - DNA is a nuclear molecule that has both an intracellular and extracellular role.
      Inside the cell, it is the essential molecule of heredity while outside the cell
      it can have immunological activity, both alone and in the context of immune
      complexes. Furthermore, extracellular DNA has information content that can be
      mined by genomic techniques. Because of the association of extracellular DNA with
      clinical conditions marked by cell death, dead and dying cells have been
      considered the origin of this material. To investigate this process, in vitro and
      in vivo systems have been used to determine the release of DNA from cells, using
      Jurkat T cells as a model. Thus, in vitro, apoptotic Jurkat cells release DNA
      whereas necrotic cells do not. The presence of macrophages in these cultures,
      however, modifies the release process, causing release from necrotic cells as
      well. In in vivo experiments in which Jurkat cells are administered to normal
      mice, both apoptotic and necrotic cells give rise to DNA in the blood in a
      process that requires macrophages and can be modified by glucocorticoids. In this
      model, female and male mice differ in the extent of DNA release from the
      administered Jurkat cells. Together, these results indicate that, while apoptosis
      and necrosis can lead to a blood DNA response, this process requires macrophages
      and may be hormonally mediated.

PMID- 17516211
TI  - HMGB1: a signal of necrosis.
AB  - When tissues are damaged, they usually heal. The cellular responses towards
      healing require the prior recognition that damage has occurred. High Mobility
      Group Box 1 protein (HMGB1) is a ubiquitous nuclear protein that is passively
      released by cells that have died in a traumatic, non-programmed way (necrosis).
      Several receptors for HMGB1 exist, and upon binding HMGB1 they alert leukocytes
      to extravasate from the blood into the affected tissue, trigger adaptive immunity
      and promote the migration and proliferation of cells (including stem cells) to
      repair the damaged tissue. Significantly, apoptotic cells modify their chromatin
      so as to bind HMGB1, which is not released. Several cell types (in particular
      inflammatory cells) when distressed have the ability to secrete HMGB1 actively,
      via a dedicated pathway, and thus produce a damage signal without dying. Because
      of its powerful activities, HMGB1 is involved in several disorders, including
      autoimmune ones.

PMID- 17516212
TI  - Signals of cell death and tissue turnover during physiological pregnancy, pre
      eclampsia, and autoimmunity.
AB  - Apoptosis normally occurs in the human placenta. As a consequence, cell blebs,
      post-apoptotic debris (also referred to as syncytial knots) and membrane
      microparticles are released into the blood of pregnant women. These events become
      prominent during the best-characterized pregnancy complication, pre-eclampsia. An
      excessive or deregulated cell death, which results in the generation of an
      overwhelming burden of apoptotic material, alarms the immune system. This plays a
      role in the pathogenesis of systemic connective tissue diseases and possibly of
      small vessels vasculitis. Infiltration of leukocytes and activation of
      endothelial cells and platelets are hallmarks of normal pregnancy, indicating
      that physiologic pregnancy is a condition characterized by an activation of the
      innate immune system. Conversely, a failure in the physiologic termination of
      inflammatory events is probably a requirement for pre-eclampsia to develop. Here,
      we discuss recent findings suggesting a link between deregulated disposal of
      placental debris, the generation of endogenous pro-inflammatory signals
      (alarmins) and the widespread vascular inflammation that characterizes on one
      hand pre-eclampsia and on the other systemic autoimmune diseases.

PMID- 17516213
TI  - CRP and the disposal of dying cells: consequences for systemic lupus
      erythematosus and rheumatoid arthritis.
AB  - C reactive protein (CRP) levels directly correlate with the disease activity of
      many inflammatory diseases, e.g. sepsis, infection, and various autoimmunopathies
      such as rheumatoid arthritis (RA). In contrast, insufficient CRP levels are
      implicated in the development of systemic lupus erythematosus (SLE). This article
      reports on the level-depended effects of CRP in various diseases. In detail we
      show that increased and decreased levels of CRP, as demonstrated in patients with
      RA and SLE, respectively can contribute to disease progression.

PMID- 17516214
TI  - The expanded double negative T cell populations of a patient with ALPS are not
      clonally related to CD4+ or to CD8+ T cells.
AB  - The autoimmune lymphoproliferative syndrome (ALPS) is characterized by non
      malignant lymphoproliferation and signs of autoimmunity. A hallmark of ALPS are
      high amounts of circulating CD3+/CD4-/CD8- double negative T-lymphocytes (DN T
      cells). The origin of these cells remains elusive. To investigate the
      relationships of DN T cells and the single positive T cell populations (CD4+ and
      CD8+), we analyzed by spectratyping the complementarity determining regions 3
      (CDR3) of the T cell receptors in sorted "single positive" (CD4+, CD8+) and DN T
      cells in a patient with ALPS type 1a. We observed signs for clonal expansion in
      all three T cell subpopulations. Strong and weak clonal expansions were to be
      seen in 16 and 14 for DN, 6 and 12 for CD8+, and 1 and 5 for CD4 + T cells,
      respectively. Most importantly, 24 out of 30 aberrant peaks in the spectratype
      histograms of the DN T cells where unique for this population and were not to be
      detected in the histograms of the single positive T cells. In contrast to
      published data, we conclude that expanded DN T cell populations in ALPS are not
      generally derived from expanded CD3+/CD4+ or CD3+/CD8+ populations.

PMID- 17516215
TI  - Requirement for dendritic cells in the establishment of anti-phospholipid
      antibodies.
AB  - OBJECTIVE: The cross-presentation of cell-associated autoantigens contributes to
      systemic autoimmune diseases, including systemic lupus erythematosus (SLE).
      Little is known about the regulation of the immune response against soluble
      autoantigens targeted in these diseases. METHODS: We immunized the offspring of
      New Zealand Black and New Zealand White mice (NZB x NZW F(1)) with syngeneic
      dendritic cells (DC) that had macropinocytosed beta2-glycoprotein 1 (beta(2)GPI)
      during propagation in normal mouse serum or that had phagocytosed apoptotic
      thymocytes with syngeneic (murine) or xenogeneic (bovine) beta(2)GPI, which was
      associated to plasma membrane of the cells. Mice were in parallel immunized with
      apoptotic thymocytes that had associated the beta(2)GPI to their membranes in the
      absence of DC. The development of anti-beta(2)GPI antibodies and clinical
      features were monitored. RESULTS: Apoptotic cells alone, opsonized with
      beta(2)GPI, failed to induce anti-beta(2)GPI autoantibodies or clinical disease.
      In contrast, autoimmunity developed in the presence of DC. Furthermore, the
      syngeneic beta(2)GPI was a more effective antigen than the xenogeneic protein in
      re-boosted animals. CONCLUSIONS: DC effectively initiate in NZB x NZW F(1) mice
      self-sustaining autoimmunity against the beta(2)GPI, either associated to
      apoptotic cells or macropinocytosed from the serum.

PMID- 17516216
TI  - Sensitive detection of plasma/serum DNA in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To optimize the use of the fluorochromic PicoGreen assay for the
      sensitive detection and quantification of double stranded (ds) DNA in
      plasma/serum samples of patients with systemic lupus erythematosus (SLE).
      METHODS: Plasma/serum samples were obtained from SLE patients and normal healthy
      donors (NHD). Plasma/serum proteins were digested with proteinase K. DNA was
      subsequently purified using silica-based ion exchange micro columns and detected
      using the PicoGreen assay. RESULTS: Sensitive detection of plasma/serum DNA is
      impaired by proteins: (1) Proteins caused background fluorescence in the
      PicoGreen assay. (2) Packaging of dsDNA in nucleosomes markedly reduced PicoGreen
      fluorescence. Therefore, we digested proteins using proteinase K and purified DNA
      before detection by PicoGreen assay. This procedure resulted in a detection limit
      for plasma/serum dsDNA of less than 1 ng/ml, and is therefore markedly more
      sensitive than previously described methods. We found that DNA concentrations are
      higher in serum than in plasma of healthy donors, suggesting artifactual DNA
      release during coagulation. In addition, we found higher levels of DNA in plasma
      and serum of a group of SLE patients compared to NHD. CONCLUSIONS: We have
      optimized the use of the PicoGreen assay for the ultrasensitive and reliable
      quantification of DNA in plasma/serum samples. This new method can be used in
      future studies to explore a possible correlation between circulating DNA levels
      and disease activity in patients with SLE.

PMID- 17516217
TI  - Circulating nucleosomes due to a defective clearance of dying cells: consequences
      for systemic lupus erythematosus.

PMID- 17516218
TI  - Engulfed cell remnants, and not cells undergoing apoptosis, constitute the LE
      cell phenomenon.
AB  - The LE cell has been one of the first immunological signs of active systemic
      lupus erythematosus, included into the ACR criteria. LE cells consist of a
      phagocyte engulfing material of disputed origin, which was interpreted as either
      cellular remnants from necrotic cells or as early apoptotic cells. It is well
      established that LE cell formation is dependent on autoantibodies against the
      linker histone H1. In view of this fact, we investigated whether anti-histone H1
      antibodies and LE cell positive sera bound to cells where apoptosis had been
      induced by gliotoxin or actinomycin D or which were necrotic after heating.
      Necrotic cell remnants, but not (early) apoptotic cells were bound by anti
      histone H1 antibodies and LE cell positive sera, establishing that the process of
      LE cell formation, which is dependent on anti-H1 binding, leads to engulfment of
      necrotic (or late apoptotic) material, but not of early apoptotic cells.

PMID- 17516219
TI  - Interaction of histones with phospholipids--implications for the exposure of
      histones on apoptotic cells.
AB  - The generation of autoantibodies against chromatin is a hallmark of the
      multifactorial autoimmune disease systemic lupus erythematosous (SLE). Impaired
      clearance of apoptotic cells together with the release of nuclear autoantigens
      are supposed to contribute to the loss of self-tolerance in SLE. Phospholipids
      such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) are exposed on
      the surfaces of apoptotic cells and on apoptotic blebs. Also histones/nucleosomes
      can be detected on apoptotic cells; however, their binding motifs are still
      unknown. Therefore, we investigated the interaction of PS, PE,
      phosphatidylcholine (PC), and cardiolipin (CL) with histones H1, H2A, H2B, H3,
      and H4 by surface plasmon resonance (SPR). Strong binding to phospholipids was
      found for all histones, with H2A displaying the highest binding affinity to all
      phospholipids investigated. Hence, phospholipids including PS and PE may
      contribute to the binding of histones to surfaces and blebs of apoptotic cells.
      Moreover, histones/nucleosomes complexed to uningested apoptotic membrane
      structures may foster autoimmunity towards nuclear compounds.

PMID- 17516220
TI  - Apoptotic cells selectively suppress the Th1 cytokine interferon gamma in
      stimulated human peripheral blood mononuclear cells and shift the Th1/Th2 balance
      towards Th2.
AB  - Apoptotic cells are readily recognized and engulfed by phagocytes and usually do
      not induce inflammation or tissue damage. Furthermore, they can actively suppress
      a pro-inflammatory response in phagocytes: In the presence of apoptotic cells,
      activated monocytes/macrophages produce more of the anti-inflammatory and
      immunoregulatory cytokines IL-10 and TGF-beta, but less of the pro-inflammatory
      cytokines TNFalpha, IL-1beta and IL-12. This immunoregulatory effect is most
      likely mediated by several receptors on monocytes/macrophages including the
      thrombospondin receptor (CD36). In addition to the modulation of cytokine
      secretion, apoptotic cell material inhibited the expression of MHC class II
      molecules on the surface of monocytes/macrophages. Decreased MHC II expression
      appeared to be mediated predominantly by increased IL-10 secretion in a para
      /autocrine manner. Here, we show that the functional modulation of antigen
      presenting monocytes/macrophages by apoptotic cells also influences T cell
      activation and function. When human peripheral blood mononuclear cells were
      stimulated with recall antigens in the presence of apoptotic cells, interferon
      gamma (IFN gamma) secretion was markedly suppressed, whereas secretion of the Th2
      cytokine IL-4 was not significantly altered. Hence, apoptotic cells shift the T
      cell cytokine secretion pattern towards a Th2-like response. This Th2 shift can
      largely be prevented by neutralizing IL-10, indicating an important role of this
      cytokine for modulating T cell cytokine secretion patterns.

PMID- 17516221
TI  - Purified apoptotic bodies stimulate plasmacytoid dendritic cells to produce IFN
      alpha.

PMID- 17516222
TI  - The lonely death: chondrocyte apoptosis in TNF-induced arthritis.
AB  - Inflammatory joint disease typically provokes progressive cartilage damage. The
      proliferative synovial inflammatory tissue directly invades the cartilage and
      induces the expression and activation of degrading enzymes such as matrix
      metalloproteases (MMPs) and aggrecanases. However, also chondrocyte apoptosis has
      been observed in cartilage samples of inflamed joints. It remains unclear whether
      this is a secondary phenomenon due to cartilage damage or a primary event
      initiated by the synovial inflammation. To determine the presence or absence of
      chondrocyte death in experimental arthritis, we longitudinally assessed
      proteoglycan depletion and chondrocyte apoptosis in paw sections from human tumor
      necrosis factor transgenic (hTNFtg) mice and wild-type littermates. Whereas, wild
      type mice showed no signs of cartilage damage, hTNFtg mice exhibited progressive
      proteoglycan loss starting at clinical onset of arthritis. However, we already
      found the first apoptotic chondrocytes well before cartilage matrix breakdown
      occurred indicating that chondrocyte death can be induced before matrix
      resorption. Chondrocyte death could constantly be observed until late stages of
      arthritis causing a continuous increase in the number of empty cartilage lacunae.
      As apoptotic cells in cartilage cannot be cleared by phagocytes due to their
      spatial isolation in the avascular lacunae of cartilage, having no contact to
      professional or amateur phagocytes. The dying cells are compelled to undergo a
      "lonely death" inevitable ending up in secondary necrosis giving rise to
      perpetuation of a pro-inflammatory cascade. These data indicate that chondrocyte
      death may play a primary role in inflammatory arthritis fueling cartilage
      inflammation and damage due to secondary necrosis.

PMID- 17516223
TI  - Opsonization by anti-dsDNA antibodies of apoptotic cells in systemic lupus
      erythematosus.
AB  - In order to asses the role of the soluble mediators of serum from patients with
      SLE in the apoptotic cell clearance, we measured the in vitro phagocytosis of
      apoptotic Jurkat cells by normal healthy donor macrophages in the presence of SLE
      patients' sera. A significant increase of the phagocytic index (NHD = 1.0 +/-
      0.3; SLE = 1.9 +/- 0.6; p < 0.01) was to be observed in the presence of serum
      from patients with SLE. The increased phagocytic index correlated to the anti
      dsDNA antibodies titers. We conclude that anti-dsDNA antibodies present in sera
      of patients with SLE favor the apoptotic cell phagocytosis by opsonization of the
      target cells. This may represent a deviation of the clearance process towards
      inflammation and a new pathologic feature of these autoantibodies in SLE.

PMID- 17516224
TI  - Apoptotic bodies derived from apoptotic lymphoblasts contain a distinct pattern
      of antigens.

PMID- 17516225
TI  - Attraction of phagocytes by apoptotic cells is mediated by
      lysophosphatidylcholine.
AB  - Apoptotic cells promote the phagocytosis of themselves via the exposure of "eat
      me" signals. Furthermore, a second, "find me" signal is required to attract
      phagocytes. In this review the double function of lysophosphatidylcholine for the
      clearance of apoptotic material as factor leading to attraction of phagocytes as
      a soluble "find me" signal and opsonisation of apoptotic cells as a membrane
      bound "eat me" signal is outlined. Lysophosphatidylcholine, exerting this
      bivalent function, leads to a sufficient clearance of apoptotic cell as a "keep
      calm" mechanism to prevent activation of the immune system by secondary necrosis.

PMID- 17516226
TI  - Sweet clearance: involvement of cell surface glycans in the recognition of
      apoptotic cells.
AB  - Glycans cover the surfaces of all mammalian cells. Their structural variety
      provides enormous potential for information storage and transfer. According to
      the concept of the sugar code, they act as biochemical signals decoded by a large
      number of lectins which are defined as sugar binding proteins. The importance of
      glycan-lectin interaction in diverse immune system functions becomes increasingly
      apparent. Here, we review apoptotic cell clearance and especially focus on
      modifications of glycans on apoptotic cells.

PMID- 17516227
TI  - Apoptosis driven infection.
AB  - Professional phagocytes like polymorphonuclear neutrophil granulocytes (PMN) and
      macrophages (MF) kill pathogens as the first line of defense. These cells possess
      numerous effector mechanisms to eliminate a threat at first contact. However,
      several microorganisms still manage to evade phagocytic killing, survive and
      retain infectivity. Some pathogens have developed strategies to silently infect
      their preferred host phagocytes. The best example of an immune silencing
      phagocytosis process is the uptake of apoptotic cells. Immune responses are
      suppressed by the recognition of phosphatidylserine (PS) on the outer leaflet of
      their plasma membrane. Taking Leishmania major as a prototypic intracellular
      pathogen, we showed that these organisms can use the apoptotic "eat me" signal PS
      to silently enter PMN. PS-positive and apoptotic parasites, in an altruistic way,
      enable the intracellular survival of the viable parasites. Subsequently these
      pathogens again use PS exposition, now on infected PMN, to silently invade their
      definitive host cells, the MF. In this review, we will focus on L. major evasion
      strategies and discuss other pathogens and their use of the apoptotic "eat me"
      signal PS to establish infection.

PMID- 17516228
TI  - Aspects of spatio-temporal variability during consonant production by Greek
      speakers with hearing impairment.
AB  - This paper investigates spatio-temporal variability during the production of the
      lingual consonants /t, k, s, x, n, l, 50% shaded block/ by four Greek speakers
      with profound hearing impairment and with differences in the intelligibility of
      their speech. It examines important factors that have been documented to
      influence intelligibility, i.e. durational variability, articulatory (token-to
      token) variability, and coarticulatory patterns. The technique of
      electropalatography was used to record tongue-palate contact patterns during
      consonant production in order to examine differences in articulatory variability
      among speakers and in V-to-C coarticulatory effects. The study reports durational
      differences in consonant production between speakers with hearing impairment and
      normal hearing and investigates the relationship between token-to-token
      variability in tongue-palate contact patterns and duration. The results indicate
      a negative relationship between duration and variability, i.e. as segmental
      duration decreases there is an increase in variability in tongue-palate contact
      patterns. Significant speaker-dependent differences in duration, articulatory
      variability and coarticulatory patterns are reported and are discussed in
      relation to differences in intelligibility among the speakers with hearing
      impairment.

PMID- 17516229
TI  - Comparability of lexical corpora: word frequency in phonological generalization.
AB  - Statistical regularities in language have been examined for new insight to the
      language acquisition process. This line of study has aided theory advancement,
      but it also has raised methodological concerns about the applicability of corpora
      data to child populations. One issue is whether it is appropriate to extend the
      regularities observed in the speech of adults to developing linguistic systems.
      The purpose of this paper is to establish the comparability of lexical corpora in
      accounting for behavioural effects of word frequency on children's phonological
      generalization. Four word frequency corpora were evaluated in comparison of
      child/adult and written/spoken sources. These were applied post-hoc to
      generalization data previously reported for two preschool children. Results
      showed that the interpretation of phonological generalization was the same within
      and across children, regardless of the corpus being used. Phonological gains were
      more evident in low than high frequency words. The findings have implications for
      the design of probabilistic studies of language acquisition and clinical
      treatment programmes.

PMID- 17516230
TI  - Non-word repetition: an investigation of phonological complexity in children with
      Grammatical SLI.
AB  - We investigate whether children with Grammatical Specific Language Impairment (G
      SLI) are also phonologically impaired and, if so, what the nature of that
      impairment is. We focus on the prosodic complexity of words, based on their
      syllabic and metrical (stress) structure, and investigate this using a novel non
      word repetition procedure, the Test of Phonological Structure (TOPhS).
      Participants with G-SLI (aged 12-20 years) were compared to language-matched,
      typically developing children (aged 4-8 years). The results reveal that, in
      contrast to the controls, the accuracy with which the G-SLI group repeated non
      words decreased as prosodic complexity increased, even in non-words with only one
      and two-syllables. The study indicates that, in G-SLI, complexity deficits in
      morphology and syntax can extend to prosodic phonology. The study highlights the
      importance of taking into account prosodic complexity in phonological assessment
      and the design of non-word repetition procedures.

PMID- 17516231
TI  - Children with autistic spectrum disorders and speech-generating devices:
      communication in different activities at home.
AB  - The communication of four children with autistic spectrum disorder was
      investigated when they were supplied with a speech-generating device (SGD) in
      three different activities in their home environment: mealtime, story reading and
      "sharing experiences of the preschool day". An activity based communication
      analysis, in which collective and individual background factors for the
      activities were outlined, was used as a basis for the discussion of linguistic
      coding data derived from video-recordings made before and during SGD
      intervention. The coded communicative behaviours were engagement in activity,
      role in turn-taking, communicative form, function and effectiveness. An increase
      in communicative effectiveness was more noticeable when the SGDs could be used to
      fulfil goals and roles within the activity. The instruction to the parents to use
      the SGDs in their communication with the child had an important influence on the
      activities.

PMID- 17516232
TI  - Temporal features of articulation from childhood to adolescence: an
      electropalatographic investigation.
AB  - This study was designed to investigate the development of articulatory timing
      from mid-childhood to late adolescence. Productions of sentences containing /t/,
      /l/, /s/, and /k/ were produced by 48 children and adults (aged 6-38 years) and
      captured using the Reading Electropalatography3 (EPG3) system. Mean duration of
      the sentences and the approach, closure/stable constriction, and release phases
      of consonant articulation were calculated. In addition, temporal coordination of
      lingual gestures and the intra-subject articulatory timing variation were
      investigated across the ages. Results reveal some distinct differences in
      duration and temporal coordination of lingual gestures between 6- to 7-year-olds
      and mature speakers, with continual refinement of articulatory control indicated
      into late adolescence. Differences in articulatory stability, in contrast, were
      not significant. The present findings may form a platform for development of a
      more descriptive model of motor speech development.

PMID- 17516233
TI  - Platinum nanoparticle is a useful scavenger of superoxide anion and hydrogen
      peroxide.
AB  - Bimetallic nanoparticles consisting of gold and platinum were prepared by a
      citrate reduction method and complementarily stabilized with pectin (CP-Au/Pt).
      The percent mole ratio of platinum was varied from 0 to 100%. The CP-Au/Pt were
      alloy-structured. They were well dispersed in water. The average diameter of
      platinum nanoparticles (CP-Pt) was 4.7 +/- 1.5 nm. Hydrogen peroxide (H(2)O(2))
      was quenched by CP-Au/Pt consisting of more than 50% platinum whereas superoxide
      anion radical (O(2)(-)) was quenched by any CP-Au/Pt. The CP-Au/Pt quenched these
      two reactive oxygen species in dose-dependent manners. The CP-Pt is the strongest
      quencher. The CP-Pt decomposed H(2)O(2) and consequently generated O(2) like
      catalase. The CP-Pt actually quenched O(2)(-) which was verified by a superoxide
      dismutase (SOD) assay kit. This quenching activity against O(2)(-) persisted like
      SOD. Taken together, CP-Pt may be a SOD/catalase mimetic which is useful for
      medical treatment of oxidative stress diseases.

PMID- 17516234
TI  - Reactions of thiocyanate in the mixture of nitrite and hydrogen peroxide under
      acidic conditions: investigation of the reactions simulating the mixture of
      saliva and gastric juice.
AB  - Nitrite and SCN(-) in saliva can mixes with H(2)O(2) in the stomach. The mixing
      can result in the formation of ONOOH. It is not yet known how salivary SCN(-)
      reacts with ONOOH. An objective of the present study was to elucidate the
      reaction between ONOOH and SCN(-). In nitrite/H(2)O(2) systems at pH 2, SCN(-)
      inhibited the consumption of nitrite and the formation of O(3)(-). SCN(-)
      enhanced the decomposition of ONOOH and H(2)O(2) in HNO(2)/H(2)O(2) systems.
      Accompanying the reactions, sulfate was formed, suggesting that ONOOH oxidized
      SCN(-). SCN(-) inhibited the nitration of phenolics induced by HNO(2)/H(2)O(2).
      The inhibition is discussed taking SCN(-)-dependent reduction of ONOOH to HNO(2)
      into consideration. SCN(-) also inhibited H(2)O(2)-induced consumption of nitrite
      and nitration of phenolics in acidified saliva. The result obtained in this study
      suggests that salivary SCN(-) can reduce ONOOH to O(2)(-)/HNO(2) inhibiting
      nitrating reactions in the stomach.

PMID- 17516235
TI  - Ursolic acid regulates high glucose-induced apoptosis.
AB  - A high concentration of glucose has been implicated as a causal factor in
      initiation and progression of diabetic complications and there is evidence to
      suggest that hyperglycemia increases the production of free radicals and
      oxidative stress. Therefore, compounds that scavenge reactive oxygen species
      (ROS) may confer regulatory effects on high glucose-induced apoptosis. Ursolic
      acid (UA), a pentacyclic triterpene, is reported to have an antioxidant activity.
      We investigated the effect of UA on high glucose-induced apoptosis in U937 cells.
      Upon exposure to 35 mM glucose for two days, there was a distinct difference
      between untreated cells and cells pre-treated with 50 nM UA for 2 h in regard to
      cellular redox status and oxidative DNA damage to cells. UA pre-treated cells
      showed significant suppression of apoptotic features such as DNA fragmentation,
      damage to mitochondrial function and modulation of apoptotic marker proteins upon
      exposure to high glucose. This study indicates that UA may play an important role
      in regulating the apoptosis induced by high glucose presumably through scavenging
      of ROS.

PMID- 17516236
TI  - The plasma concentration of advanced oxidation protein products and arterial
      stiffness in apparently healthy adults.
AB  - BACKGROUND: Oxidative stress plays an important role in the pathogenesis of
      atherosclerosis. Advanced oxidation protein products (AOPP) are markers of
      oxidative stress and mediators of inflammation. Increased arterial stiffness is
      associated with increased risk of cardiovascular mortality and morbidity. The aim
      of this study was to evaluate the relationship between an indirect marker of
      arterial stiffness and the AOPP level in apparently healthy individuals. METHODS
      AND RESULTS: Arterial stiffness was estimated with the use of the stiffness index
      (SI(DVP)) which significantly correlated with age, mean blood pressure, body fat
      content and AOPP. The SI(DVP) was associated with AOPP concentration in both
      single (R = 0.22, p = 0.03) and multiple regression models adjusted for age, sex,
      mean blood pressure and body fat content (R(2) = 42%, p < 0.0001). CONCLUSIONS:
      The AOPP concentration is elevated in healthy people with increased values of
      stiffness index. This finding supports the concept that oxidative stress may
      contribute to arterial stiffening in humans.

PMID- 17516237
TI  - Identification of a radical formed in the reaction mixture of rat brain
      homogenate with a ferrous ion/ascorbic acid system using HPLC-EPR and HPLC-EPR
      MS.
AB  - Identification of a free radical is performed for the reaction mixture of rat
      brain homogenate with a ferrous ion/ascorbic acid system using EPR, high
      performance liquid chromatography-electron paramagnetic resonance spectrometry
      (HPLC-EPR) and high performance liquid chromatography-electron paramagnetic
      resonance-mass spectrometry (HPLC-EPR-MS). EPR measurements of the reaction
      mixtures showed prominent signals with hyperfine coupling constants (alpha(N) =
      1.58 mT and alpha(H)beta = 0.26 mT). No EPR spectrum was detectable without rat
      brain homogenate, suggesting that the radical is derived from rat brain
      homogenate. An HPLC-EPR analysis of the reaction mixture showed a peak with
      retention time of 33.7 min. An HPLC-EPR-MS analysis of the peak gave two ions at
      m/z 224 and 137, suggesting that alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4
      POBN)/ethyl radical adduct forms in the reaction mixture.

PMID- 17516238
TI  - 8-oxo-7,8-dihydroguanosine triphosphate(8-oxoGTP) down-regulates respiratory
      burst of neutrophils by antagonizing GTP toward Rac, a small GTP binding protein.
AB  - 8-oxo-7,8-dihydroguanosine triphosphate (8-oxoGTP) has been regarded simply as a
      oxidative mutagenic byproduct. The results obtained in this study imply that it
      may act as a down-regulator of respiratory burst of neutrophils. Human
      neutrophils treated with PMA produced superoxides and at the same time, the
      cytosol of these cells was intensely immunostained by 8-oxo-7,8
      dihydroguanosine(8-oxoG) antibody, indicating that 8-oxoG-containing chemical
      species including 8-oxoGTP are produced. Human neutrophil lysates treated with
      PMA also produced superoxides, which was stimulated by GTPgammaS but inhibited by
      8-oxoGTPgammaS. Moreover, 8-oxoGTPgammaS suppressed the stimulatory action of
      GTPgammaS. Likewise, GTPgammaS stimulated Rac activity in neutrophil lysates but
      8-oxoGTPgammaS and GDP inhibited it. The inhibitory effect of GDP was one tenth
      that of 8-oxoGTPgammaS. Here again, 8-oxoGTPgammaS also suppressed the
      stimulatory action of GTPgammaS on Rac activity. These results imply the
      possibility that 8-oxoGTP is formed during respiratory burst of neutrophils and
      limits neutrophil production of superoxides by antagonizing GTP toward Rac.

PMID- 17516239
TI  - Adrenaline stimulates H2O2 generation in liver via NADPH oxidase.
AB  - It is known that adrenaline promotes hydroxyl radical generation in isolated rat
      hepatocytes. The aim of this work was to investigate a potential role of NADPH
      oxidase (Nox) isoforms for an oxidative stress signal in response to adrenaline
      in hepatocytes. Enriched plasma membranes from isolated rat liver cells were
      prepared for this purpose. These membranes showed catalytic activity of Nox
      isoforms, probably Nox 2 based on its complete inhibition with specific
      antibodies. NADPH was oxidized to convert O(2) into superoxide radical, later
      transformed into H(2)O(2). This enzymatic activity requires previous activation
      with either 3 mM Mn(2+) or guanosine 5'-0-(3-thiotriphosphate) (GTPgammaS) plus
      adrenaline. Experimental conditions for activation and catalytic steps were set
      up: ATP was not required; S(0.5) for NADPH was 44 microM; S(0.5) for FAD was 8
      microM; NADH up to 1 mM was not substrate, and diphenyleneiodonium was
      inhibitory. Activation with GTPgammaS plus adrenaline was dose- and Ca(2+)
      dependent and proceeded through alpha(1)-adrenergic receptors (AR), whereas beta
      AR stimulation resulted in inhibition of Nox activity. These results lead us to
      propose H(2)O(2) as additional transduction signal for adrenaline response in
      hepatic cells.

PMID- 17516240
TI  - Oxidative inactivation of the proteasome in Alzheimer's disease.
AB  - In the present study we isolated proteasome complexes from control, mild
      cognitive impairment (MCI), and Alzheimer's disease (AD) subjects. No significant
      difference in the amount of proteasomes was detected across the different groups,
      although impairments in chymotrypsin-like proteasome activity was observed in AD
      subjects. Large impairments in proteasome- mediated degradation of an oxidized
      protein substrate was observed in MCI and AD subjects. Incubation with a reducing
      agent (DTT) had no significant effect on proteasome chymotrypsin-like activity,
      but fully restored proteasome-mediated protein degradation in MCI and AD
      subjects. Proteasomes from AD subjects exhibited elevations in protein carbonyls,
      4-hydroxynonenal-conjugation, and neuroprostane-conjugation. Together, these data
      confirm that impairments in the function of purified proteasomes occurs in the
      earliest stages of AD, and directly support a role for oxidative inactivation
      contributing to declines in proteasome function in AD.

PMID- 17516241
TI  - Phospholipid hydroperoxide glutathione peroxidase (PHGPx) expression is
      downregulated in poorly differentiated breast invasive ductal carcinoma.
AB  - Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) is the only known
      enzyme able to reduce lipid peroxides bound to cell membranes. Moreover it has
      been involved in apoptosis and can influence intracellular signaling. To
      investigate the possible relationship between PHGPx and human cancer we have
      quantified PHGPx expression levels by real-time quantitative PCR and
      immunohistochemistry in tissue samples of human breast invasive ductal carcinoma
      from 34 patients compared with their own controls of benign breast tissue. PHGPx
      expression levels were compared with the clinical and pathological data of these
      patients. The results showed that PHGPx expression levels are downregulated in
      poorly differentiated (grade 3) breast invasive ductal carcinoma (P = 0.0043).
      PHGPx expression levels decreased gradually with tumor grade from grade 1 to
      grade 3. We also found a downregulation of PHGPx in cases that showed p53
      accumulation compared with cases without p53 immunostaining (P = 0.0011). PHGPx
      was also downregulated in cases without progesterone receptors (PR)
      immunostaining compared with cases with PR immunostaining (P = 0.0165). Grade 3,
      p53 immunostaining and absence of PR immunostaining are poor prognostic factors.
      These results suggest that PHGPx downregulation could be related with a poorer
      prognosis in breast invasive ductal carcinoma.

PMID- 17516242
TI  - Impairment of thioredoxin reductase activity by oxidative stress in human
      rheumatoid synoviocytes.
AB  - The thioredoxin/thioredoxin reductase system is strongly induced in patients with
      rheumatoid arthritis (RA). We have investigated the impact on TR activity of
      doses of superoxide anion generated by the hypoxanthine (HX)/xanthine oxidase
      (XO) system and by hydrogen peroxide, H(2)O(2), for various times and compared
      the findings with synoviocytes obtained from osteoarthritis (OA) patients. At
      baseline, TR activity in RA cells was significantly higher than in OA cells (2.31
      +/- 0.65 versus 0.74 +/- 0.43 mUnit/mg protein, p < 0.01). HX/XO and H(2)O(2) in
      RA cells decreased TR activity, which was found to be unchanged in OA cells.
      H(2)O(2) and superoxide anion caused a time-dependent accumulation of oxidized TR
      and induced the formation of carbonyl groups in TR protein in RA cells rather
      than OA cells, and oxidized the selenocysteine of the active site. The oxidation
      in TR protein was irreversible in RA cells but not in OA cells. In conclusion, we
      report that the oxidative aggression generates modifications in the redox status
      of the active site of the TR and induces an alteration of the Trx/TR system,
      concomitant with those of the other antioxidant systems that could explain the
      causes of oxidative stress related to RA disease.

PMID- 17516243
TI  - Analysis of dihydroethidium fluorescence for the detection of intracellular and
      extracellular superoxide produced by NADPH oxidase.
AB  - All methods used for quantitation of superoxide have limitations when it comes to
      differentiating between extracellular and intracellular sites of superoxide
      production. In the present study, we monitored dihydroethidium (DHE)-derived
      fluorescence at 570 nm, which indicates hydroxyethidium derived from reaction
      with superoxide produced by human leukemia cells (HL-60) and microvascular
      endothelial cells (HMEC-1). Phorbol-12-myristate 13-acetate (PMA; 100 ng/ml)
      caused an increase in fluorescence and lucigenin chemiluminescence in HL-60,
      which was abolished by superoxide dismutase (SOD; 600 U/ml) indicating that DHE
      detects extracellular superoxide. Furthermore, both HL-60 cells and HMEC-1
      generated a fluorescence signal in the presence of DHE under resting conditions,
      which was unaffected by SOD, but abolished by polyethylene glycosylated-SOD (PEG
      SOD) (100 U/ml) and MnTmPyP (25 microM), indicating that DHE also detects
      superoxide produced intracellularly. In HMEC-1, silencing of either Nox2 or Nox4
      components of NADPH oxidase with small interference RNA (siRNA) resulted in a
      significant reduction in superoxide detected by both DHE fluorescence (Nox2
      siRNA; 71 +/- 6% and Nox4 siRNA 83 +/- 7% of control) and lucigenin
      chemiluminescence (Nox2; 54 +/- 6% and Nox4 74 +/- 4% of control). In conclusion,
      DHE-derived fluorescence at 570 nm is a convenient method for detection of
      intracellular and extracellular superoxide produced by phagocytic and vascular
      NADPH oxidase.

PMID- 17516244
TI  - Hypochlorous acid generates N epsilon-(carboxymethyl)lysine from Amadori
      products.
AB  - Since the accumulation of N(epsilon)-(carboxymethyl)lysine (CML), a major
      antigenic advanced glycation end product, is implicated in tissue disorders in
      hyperglycemia and inflammation, the identification of the pathway of CML
      formation will provide important information regarding the development of
      potential therapeutic strategies for these complications. The present study was
      designed to measure the effect of hypochlorous acid (HOCl) on CML formation from
      Amadori products. The incubation of glycated human serum albumin (glycated-HSA),
      a model of Amadori products, with HOCl led to CML formation, and an increasing
      HOCl concentration and decreasing pH, which mimics the formation of these
      products in inflammatory lesions. CML formation was also observed when glycated
      HSA was incubated with activated neutrophils, and was completely inhibited in the
      presence of an HOCl scavenger. These data demonstrated that HOCl-mediated CML
      formation from Amadori products plays a role in CML formation and tissue damage
      at sites of inflammation.

PMID- 17516245
TI  - Inhibitory effects of glycitein on hydrogen peroxide induced cell damage by
      scavenging reactive oxygen species and inhibiting c-Jun N-terminal kinase.
AB  - The present study investigated the cytoprotective properties of glycitein, a
      metabolite formed by the transformation of glycitin by intestinal microflora,
      against oxidative stress. Glycitein was found to scavenge intracellular reactive
      oxygen species (ROS), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and
      thereby preventing lipid peroxidation and DNA damage. Glycitein inhibited
      apoptosis of Chinese hamster lung fibroblast (V79-4) cells exposed to hydrogen
      peroxide (H(2)O(2)) via radical scavenging activity. Glycitein abrogated the
      activation of c-Jun N-terminal kinase (JNK) induced by H(2)O(2) treatment and
      inhibited DNA binding activity of activator protein-1 (AP-1), a downstream
      transcription factor of JNK. Taken together, these findings suggest that
      glycitein protected H(2)O(2) induced cell death in V79-4 cells by inhibiting ROS
      generation and JNK activation.

PMID- 17516246
TI  - Generation of superoxide and singlet oxygen from alpha-tocopherolquinone and
      analogues.
AB  - Three potential routes to generation of reactive oxygen species (ROS) from alpha
      tocopherolquinone (alpha-TQ) have been identified. The quinone of the water
      soluble vitamin E analogue Trolox C (Trol-Q) is reduced by hydrated electron and
      isopropanol alpha-hydroxyalkyl radical, and the resulting semiquinone reacts with
      molecular oxygen to form superoxide with a second order rate constant of 1.3 x
      10(8) dm(3)/mol/s, illustrating the potential for redox cycling. Illumination (UV
      A, 355 nm) of the quinone of 2,2,5,7,8-pentamethyl-6-hydroxychromanol (PMHC-Q)
      leads to a reactive short-lived (ca. 10(- 6) s) triplet state, able to oxidise
      tryptophan with a second order rate constant greater than 10(9) dm(3)/mol/s. The
      triplet states of these quinones sensitize singlet oxygen formation with quantum
      yields of about 0.8. Such potentially damaging reactions of alpha-TQ may in part
      account for the recent findings that high levels of dietary vitamin E
      supplementation lack any beneficial effect and may lead to slightly enhanced
      levels of overall mortality.

PMID- 17516247
TI  - Purification and characterization of an immunomodulatory Peptide from bovine
      placenta water-soluble extract.
AB  - An immunomodulatory peptide was isolated from bovine placenta water-soluble
      extract and purified by consecutive chromatography on DEAE Sepharose CL-6B,
      Sephadex G-25, and Sephasil C18 column using lymphocyte proliferation assay to
      identify the active fractions. The immunomodulatory peptide showed a dose
      dependent stimulating effect on lymphocyte proliferation. The isoelectric point
      of the immunodulatory peptide was determined to be 3.82 by capillary isoelectric
      focusing electrophoresis. The molecular mass of the immunomodulatory peptide was
      determined to be 2133.52 Da by mass spectrometry. The first 10 amino acid
      sequence of the immunomodulatory peptide was Tyr-X-Phe-Leu-Gly-Leu-Pro-Gly-X-Thr.
      This immunomodulatory peptide showed no significant homology with other
      immunomodulatory peptides. Additionally, it was thermostable, retaining about 60%
      of immune activity after incubating at 80 degrees C for 30 min.

PMID- 17516248
TI  - Preparative isolation and purification of hydroxyanthraquinones from Rheum
      tanguticum Maxim. on normal phase silica gel: using a Flash Master Personal
      system.
AB  - A flash chromatography method for preparative separation and purification of five
      hydroxyanthraquinones from the Chinese medicinal herb Rheum tanguticum Maxim. ex
      Balf. was developed by using Flash Master Personal(+) systems. The purities of
      the products, chrysophanol, physcion, emodin, aloe-emodin, and rhein were all
      over 90%, determined by high performance liquid chromatography (HPLC). Their
      structures were ascertained by EI-MS, (1)H- and (13)C-NMR data, and by co-TLC and
      HPLC with the authentic samples available in our laboratory.

PMID- 17516249
TI  - Optimization of alpha-amylase immobilization in calcium alginate beads.
AB  - alpha-Amylase enzyme was produced by Aspergillus sclerotiorum under SSF
      conditions, and immobilized in calcium alginate beads. Effects of immobilization
      conditions, such as alginate concentration, CaCl(2) concentration, amount of
      loading enzyme, bead size, and amount of beads, on enzymatic activity were
      investigated. Optimum alginate and CaCl(2) concentration were found to be 3%
      (w/v). Using a loading enzyme concentration of 140 U mL(-1), and bead (diameter 3
      mm) amount of 0.5 g, maximum enzyme activity was observed. Beads prepared at
      optimum immobilization conditions were suitable for up to 7 repeated uses, losing
      only 35% of their initial activity. Among the various starches tested, the
      highest enzyme activity (96.2%) was determined in soluble potato starch
      hydrolysis for 120 min at 40 degrees C.

PMID- 17516250
TI  - Functional expression and purification of bovine enterokinase light chain in
      recombinant Escherichia coli.
AB  - Enterokinase (EC 3.4.21.9) is a serine proteinase of the intestinal brush border
      that exhibits specificity for the sequence (Asp)(4)-Lys and converts trypsinogen
      into its active form, trypsin. A codon optimized sequence coding light chain
      (catalytic subunit) of bovine enterokinase gene (sBEKLC) was synthesized, and it
      was fused with DsbA to construct the expression vector (pET39-sBEKLC). Then, the
      plasmid was transformed into E. coli BL21 (DE3) for expression. Under optimal
      conditions, the volumetric productivity of fusion protein reached 151.2 mg L(-1),
      i.e., 80.6 mg sBEKLC L(-1). The cold osmotic shock technique was successfully
      used to extract sBEKLC from periplasmic space, and nickel affinity chromatography
      was employed to obtain mature sBEKLC. Finally, about 6.8 mg of bioactive sBEKLC
      was purified from 1 liter fermentation broth and could be used to cleave one
      tested fusion protein with an inter-domain enteropeptidase recognition site. This
      work will be helpful for large-scale production of this increasingly demanded
      enterokinase.

PMID- 17516251
TI  - Use of amaranthus leucocarpus lectin to differentiate cervical dysplasia (CIN).
AB  - Alterations in O-glycosylation of proteins in cell surfaces can originate
      disorder in cellular function, as well as in cell transformation and tumoral
      differentiation. In this work, we investigate changes in O-glycosylation in
      cervical intraepithelial dysplasia (CIN) at different stages of differentiation
      (CIN I, CIN II, and CIN III) using lectins specific for O-glycosidically linked
      glycans. Twenty cases with CIN I, CIN II, and CIN III dysplasias each, and 20
      normal cases were studied by lectin histochemistry and evaluated under optical
      microscopy. The lectins from Glycine max and Griffonia simplicifolia showed no
      differences in their recognition pattern among the different CIN stages and
      normal tissue. Dolichos Biflorus lectin recognized CIN I dysplasia. Lectin from
      Amaranthus leucocarpus showed increased reactivity in the presence of CIN II
      dysplasia, compared with CIN I and CIN III. These results suggest that subtle
      modifications in the O-glycosylation pattern could be considered in diagnosis or
      prognosis of cervical precancerous stages.

PMID- 17516252
TI  - Purification and some kinetic properties of catalase from parsley (Petroselinum
      hortense Hoffm., Apiaceae) leaves.
AB  - In this study, catalase (CAT: EC 1.11.1.6) was purified from parsley
      (Petroselinum hortense) leaves; analysis of the kinetic behavior and some
      properties of the enzyme were investigated. The purification consisted of three
      steps, including preparation of homogenate, ammonium sulfate fractionation, and
      fractionation by DEAE-Sephadex A50 ion exchange chromatography. The enzyme was
      obtained with a yield of 9.5% and had a specific activity of 1126 U (mg
      proteins)(-1). The overall purification was about 5.83-fold. A temperature of 4
      degrees C was maintained during the purification process. Enzyme activity was
      spectrophotometrically measured at 240 nm. In order to control the purification
      of the enzyme, SDS-polyacrylamide gel electrophoresis was carried out in 4% and
      10% acryl amide for stacking and running gel, respectively. SDS-polyacrylamide
      gel electrophoresis showed a single band for the enzyme. The molecular weight was
      found to be 183.29 kDa by Sephadex G-200 gel filtration chromatography. The
      stable pH, optimum pH, and ionic strength were determined for phosphate and Tris
      HCl buffer systems. In addition, K(M) and V(max) values for H(2)O(2), at optimum
      pH and 25 degrees C, were determined by means of Lineweaver-Burk plots.

PMID- 17516253
TI  - Growth and rutin production in hairy root cultures of buckwheat (Fagopyrum
      esculentum M.).
AB  - Buckwheat (Fagopyrum esculentum Moench.) is a potentially important source of
      rutin, a natural flavonoid with antihyperglycemic, antihypertensive, and
      antioxidative properties. To examine in vitro production of rutin, we established
      a hairy root culture of buckwheat by infecting leaf explants with Agrobacterium
      rhizogenes R1000, and tested the growth conditions and rutin production rates of
      these cultures. Ten hairy root clones were established; their growth and rutin
      production rates ranged from 233 to 312 (mg dry wt per 30 mL flask, and 0.8 to
      1.2 (mg/g dry wt), respectively. Clone H8, which had high growth and rutin
      production rates (312 mg dry wt per 30 mL flask and 1.2 mg/g dry wt,
      respectively), was selected for further experiments. H8 showed maximal growth and
      rutin content at 30 days in culture in MS medium. Of four tested culture media,
      half-strength MS medium was found to induce the highest levels of growth (378 mg
      dry wt per 30 mL flask) and rutin production (1.4 mg/g dry wt) by clone H8. In
      contrast, supplementation with auxins (0.1-1 mg/l IAA, IBA and NAA) increased the
      growth rate, but had no significant effect on rutin production by H8.
      Collectively, these findings indicate that hairy root cultures of buckwheat
      culture could be a valuable alternative approach for rutin production.

PMID- 17516254
TI  - Balance between aerobic and anaerobic metabolites production of Amycolatopsis
      orientalis depending on initial glucose concentration.
AB  - The effect of glucose concentration as a carbon source in the range of 5-20 g/L
      on the fermentative productions of intra-and extra-cellular ethanol, acetate,
      formate, oxalate, lactate, and pyruvate, as well as pyruvate decarboxylase in A.
      orientalis were investigated, depending on the incubation period. Intra-and extra
      cellular pyruvate levels increased with rising glucose concentrations up to 15
      and 20 g/L of glucose, respectively. In addition, intra-cellular pyruvate levels
      reached their maximum on the 48th hour in the range of 12.5-20 g/L of glucose,
      except for 5 and 10 g/L while extra-cellular pyruvate were at the 48th and 60th
      hours. As a fermentative end product, intra-and extra-cellular ethanol levels
      increased with increasing glucose concentrations of the growth medium and with
      incubation period. Activity of pyruvate decarboxylase, one of the key enzymes of
      the alcoholic fermentation, increased significantly with increasing glucose
      concentrations up to the 48th hour. Intra-and extra-cellular acetate levels
      increased significantly with increasing glucose concentrations of the growth
      medium and reached their maximums on the 48th hour, as was the case also for
      pyruvate. Intra-cellular formate levels increased up to 15 g/L, while extra
      cellular levels increased with increasing glucose concentration. The maximum
      intra-and extra-cellular lactate levels were determined at 12.5 g/L and 20 g/L of
      glucose on the 48th hour, respectively. The results suggest that elevated ethanol
      production suppressed lactate and formate production, supported via possibly
      formed CO(2). In addition, pyruvate, as well as acetate, were used as carbon
      sources due to the depletion of glucose contents in the growth medium.

PMID- 17516255
TI  - Immobilization of lipase to chitosan beads using a natural cross-linker.
AB  - Genipin, a reagent of plant origin was used for the immobilization of lipase by
      cross-linking to chitosan beads. The catalytic properties and operational and
      storage stabilities of the immobilized lipase were compared with the soluble
      lipase. Under optimum conditions, 198 microg protein was bound per g chitosan
      with a protein-coupling yield of 35%. The hydrolytic activity was 10.8 U/g
      chitosan and the relative specific activity was 108%. The immobilized lipase
      showed better thermal and pH stabilities compared to the soluble form. The
      immobilized enzyme exhibited mass transfer limitations as reflected by a higher
      apparent K(m) value and a lower energy of activation. The immobilized enzyme
      retained about 74% of its initial activity after five hydrolytic cycles.

PMID- 17516256
TI  - Caprine (Capra hircus) luteinizing hormone: purification and chromatographic
      investigation of its different isoforms.
AB  - Luteinizing Hormone (LH) from goat pituitary glands has been purified and
      characterized with respect to its size and subunit nature. The purification at
      each step was monitored by protein estimation, SDS-PAGE, and direct binding
      ELISA. The final product was found to be over 90 fold purified as compared to the
      starting pituitary extract, and the yield of the final purified LH was found to
      be 65.3 mg/kilogram of wet pituitary glands. Fractionation of the cLH into
      different charge isoforms by SP-Sephadex ion exchanger has been observed.
      Chromatography on immobilized Con A lectin resulted in fractionation of the
      purified cLH into unbound (2%), loosely bound (85%), and firmly bound (13%)
      fractions indicating oligosaccharide heterogeneity. The purified hormone was
      capable of stimulating weight increase in the seminal vesicles in immature male
      rats, with a biopotency equivalent to the 2200 I.U. of hCG per mg of purified
      cLH. The FSH content of the purified cLH was found to be less than 0.0165% as
      indicated by in vivo Steelman-Pohley assay.

PMID- 17516259
TI  - [The responsibility of the ophthalmologist when using drugs which are uneconomic
      from the perspective of the pharmaceutical industry].

PMID- 17516260
TI  - [RNA interferences therapeutics: a new approach to the treatment of ocular
      diseases].

PMID- 17516261
TI  - [The new role of the professor and student in the European Space of Higher
      Education].

PMID- 17516262
TI  - [Correlation between intraocular pressure, paquimetry and keratometry in a normal
      population].
AB  - PURPOSE: To study the intraocular pressure (IOP), the corneal thickness and the
      corneal curvature distribution in a normal population. To investigate the
      relation between these variables, and to determine if the IOP and the paquimetry
      will be modified by the refractive error and age. METHODS: A population of 273
      subjects, 545 eyes, without ocular pathology was selected. The refractive error,
      the corneal curvature, the corneal thickness and the IOP [with a non-contact
      tonometer (NCT) and with a Goldmann tonometer (GT)] were evaluated. RESULTS: The
      average age of the population was 49.34 (SD 7.23) years (27-68). The average
      corneal thickness was 544.3 (SD 33) mm in females and 543.1 (SD 29) mm in males.
      An inverse correlation was found between corneal thickness and age but this was
      not significant statistically. A mildly statistically significant correlation was
      found between corneal thickness and intraocular pressure with both methods of
      measurement of IOP: r = 0.316 (p < 0,001) and r = 0.264 (p < 0,001), with NCT and
      GT respectively. No correlation was found between corneal thickness and
      refractive error, or with mean corneal curvature. In the regression model,
      corneal thickness and mean corneal curvature were significant in the IOP
      prediction: R = 0.341 (p < 0.001). CONCLUSION: Mean corneal thickness was very
      similar to that reported in other studies of a latin population. A statistically
      significant inferior corneal thickness has been found in people older than 54
      years. The relationship between the corneal thickness and the corneal curvature
      with the IOP has been calculated by linear regression analyses.

PMID- 17516263
TI  - [Rebound tonometry in a clinical setting. Comparison with applanation tonometry].
AB  - PURPOSE: Rebound tonometry has recently been modified for its use in humans. The
      purpose of our study was to determine the precision of the ICare(R) rebound
      tonometer (RBT) as compared with the Goldmann applanation tonometer (GAT).
      METHODS: Patients were recruited from our Hospital's Glaucoma Unit. In each
      patient, intraocular pressure (IOP) was measured without anaesthesia using the
      RBT and ten minutes later using the GAT. Central corneal thickness (CCT) was
      measured by pachymetry. RESULTS: Sixty-eight patients were recruited (132 eyes).
      Mean IOP readings with RBT were 18.9 +/- 7.2 (SD) mmHg and were 15.5 +/- 5.7 mmHg
      with GAT (p<0.001). There was a good correlation between both instruments (r =
      0.87, p<0.001). In most cases (84.6%) the IOP measured with the RBT was greater
      than that measured with the GAT. The mean difference between both instruments was
      3.4 +/- 3.6 mmHg. There was a trend towards greater differences between those
      obtained using the RBT than the GAT when IOP values were higher. A statistically
      significant correlation was found between IOP readings with both tonometers and
      CCT, with higher differences being seen as the CCT increased. CONCLUSION: The RBT
      can be employed in a clinical setting taking into account that it usually
      overestimates IOP as compared with the GAT. It could be especially useful in
      glaucoma screening campaigns since it can be operated by a trained technician.

PMID- 17516264
TI  - [Urgent retinal detachment management by the National Health System of Spain.
      Project Retina 2].
AB  - OBJECTIVE: To identify problems in the urgent management of retinal detachments
      (RD) in hospitals of the Spanish National Health System (NHS). METHODS: A
      questionnaire was submitted confidentially to the heads of Ophthalmic Departments
      of 217 hospitals of the NHS to obtain information on the management of urgent RD
      during the last year. Data was stored in a Microsoft Access database and
      statistically analyzed by Excel and Statgraphics. Qualitative variables were
      analyzed by Chi-Square and Fisher exact tests and quantitative variables by the
      Kruskall-Wallis test. RESULTS: A global response rate of 54.8% was achieved with
      higher participation of the Teaching Hospitals (TH). District Hospital and non
      Teaching Hospital responses were similar and grouped as non-TH. Eighteen percent
      of centers, mostly non-TH, had no ophthalmologist on duty. Thirty-six percent had
      a vitreoretinal specialist on call. Eighty percent of centres admitted to have
      problems handling urgent RD during weekends. Twenty-four had no ophthalmic
      surgical theatre available. Fifty percent referred to have problems having an
      anaesthesiologist available and only 22% had ophthalmic trained personnel
      (nurses) available. Sixty-four percent of centres performed pars plana vitrectomy
      (PPV) and 77% of those were able to perform an urgent PPV. Ninety percent
      admitted that a patient with a macula-threatening RD occurring at the beginning
      of the week-end would not be treated until at least 24 hours had elapsed,
      although 84% considered this to be inadequate. CONCLUSION: Despite the
      methodological problems and bias of this questionnaire, we did identify several
      important problems in the management of urgent RD by NHS hospitals. The data
      obtained provides useful information to enable the quality of the NHS care of RD
      to be improved, particularly that available at the week-end.

PMID- 17516265
TI  - [Combined topical plus subconjunctival anesthesia versus retrobulbar anesthesia
      in non-penetrating sclerectomy].
AB  - PURPOSE: To compare the safety and efficacy of topical plus subconjunctival
      versus retrobulbar anesthesia for primary non-penetrating sclerectomy
      supplemented with adjuntive 5-FU. METHODS: A prospective study of 30 consecutive
      patients who were randomized to receive subconjunctival (n = 14) or retrobulbar
      (n = 16) anesthesia was performed. Operating conditions, patient comfort,
      postoperative pain, total pain and surgical outcomes were evaluated. RESULTS:
      There were no differences in the operating conditions. The retrobulbar group
      reported significantly more pain during administration of the anesthetic agent
      than the subconjunctival group (P= 0.00). The subconjunctival group reported more
      discomfort during surgery than the retrobulbar group (P= 0.00); however, this
      feature was not a problem for the surgeon. No statistically significant
      differences were found in regard to the total pain experienced, the postoperative
      pain, nor the success rates of the operative procedure in either group.
      CONCLUSION: Topical/subconjunctival anesthesia is a safe and effective
      alternative to retrobulbar anesthesia for non penetrating sclerectomy
      supplemented with 5-FU.

PMID- 17516266
TI  - [Acute posterior multifocal placoid pigment epitheliopathy. Study of 16 cases].
AB  - OBJECTIVE: Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) is
      a rare disease with a probable inflammatory component which mostly affects young
      patients. The aim of our study was to analyse the demographic and clinical
      features of this disease in a group of 16 patients. METHODS: Sixteen patients
      with APMPPE were included in this study. We analyzed their demographic data (age,
      sex) and the most relevant clinical findings: visual acuity and retinal disease
      outcome, association with other systemic diseases and response to treatment. We
      also collected data from fluorescence angiography, autofluorescence and optical
      coherence tomography (OCT) in some of the patients. RESULTS: Average age at
      diagnosis was 26.75 years with no sex predilection. Average final visual acuity
      (Snellen Scale) in our study was 0.73. Four patients presented with a systemic
      disease related to the APMPPE. Eleven patients were treated with oral steroids
      (one patient with steroids and cytotoxic agents) while the remaining 5 patients
      received no treatment. CONCLUSIONS: In our patients, the average age at diagnosis
      was less than 30 years, with no sex predilection, as previously described by many
      authors. The visual outcome is usually good regardless of the treatment given,
      although there are cases with a bad visual outcome, especially those with foveal
      involvement when initially seen.

PMID- 17516267
TI  - [Visual hallucinations secondary to ciprofloxacin treatment].
AB  - CASE REPORT: We describe a case of a 74-year-old woman who experienced visual
      hallucinations after ciprofloxacin administration, when she was also taking
      theophylline, which resolved on cessation of the ciprofloxacin. DISCUSSION:
      Although uncommon, all ophthalmologists should be aware of this potential problem
      and be familiar with the adverse visual effects which may occur in patients
      simultaneously administered quinolones and theophylline.

PMID- 17516268
TI  - [Bilateral papilledema secondary to chronic lymphocytic leukaemia].
AB  - CASE REPORT: We present the case of a 65-year-old man who was seen in the
      casualty department complaining of bilateral visual loss. His past medical
      history was unremarkable except for chronic lymphocytic leukaemia diagnosed two
      years previously: he was no longer receiving treatment for this disorder. His
      visual acuity was 20/200 in the right eye and 20/63 in the left eye and he had a
      bilateral papilledema. Computed tomography and magnetic resonance imaging of the
      brain and orbit were performed and showed an infiltrative mass in the orbit with
      extension to the ethmoid bone and both optic nerves. Biopsy of the mass was
      compatible with chronic lymphocytic leukaemia. DISCUSSION: Leukaemic infiltration
      of the optic nerve and central nervous system is a rare complication of chronic
      lymphocytic leukaemia, although it is common in the acute forms of this disease.
      Optic nerve infiltration is the most important ophthalmologic manifestation of
      leukaemia because it threatens vision and it is treatable.

PMID- 17516269
TI  - [Acute macular neuroretinopathy].
AB  - CLINICAL CASE: A 22-year-old woman complained of symptoms consistent with the
      sudden onset of central scotomas in both eyes after a flu-like illness. The
      typical reddish brown macular lesions of acute macular neuroretinopathy were
      evident in the parafoveal area of both eyes. Visual field examination revealed
      central scotomas in both eyes that corresponded in location to the retinal
      injuries. DISCUSSION: Acute macular neuroretinopathy is a rare idiopathic
      posterior uveitis for which no effective treatment is available. Several
      pathogenic theories are postulated.

PMID- 17516270
TI  - [Pathognomonic chorioretinal lacunar lesions in an infant with Aicardi's
      syndrome].
AB  - CLINICAL CASE: We report the case of an 81-day-old female infant who was brought
      to the Emergency Department because of a seizure. At 20 weeks of gestational age
      she was diagnosed to have agenesis of the corpus callosum, with this being
      confirmed later by magnetic resonance imaging. Ophthalmological examination of
      the fundus showed peripapillar chorioretinal lesions (lacunar chorioretinopathy)
      in both eyes. DISCUSSION: Chorioretinal lacunar and retinal pigment epithelial
      abnormalities are the basis for the diagnosis of this syndrome.

PMID- 17516271
TI  - [Brown-McLean syndrome after insertion of an anterior chamber intraocular lens:
      description of one case].
AB  - CASE REPORT: We report one case of Brown-McLean syndrome. DISCUSSION: In this
      case, a 71-year-old male developed a Brown-McLean syndrome after implantation of
      an anterior chamber lens in one aphakic eye. A phacoemulsification procedure was
      performed in the other eye without development of corneal clearance alterations
      in the next 7 years. The cause of Brown-McLean syndrome is still unexplained. It
      is possible that it could develop in eyes with a genetic predisposition when
      these eyes are exposed to certain conditions, such as insertion of an anterior
      chamber lens.

PMID- 17516272
TI  - [Instruments for cataract surgery].

PMID- 17516273
TI  - [Goya's engravings of blind people].

PMID- 17516274
TI  - [Chronic abdominal liver abscess caused by toothpick perforation of the
      gastrointestinal wall].

PMID- 17516275
TI  - Clinical value of transrectal ultrasound in the diagnosis of suspected neoplasia
      in the small pelvis.
AB  - PURPOSE: In daily clinical practice, it is challenging to accurately diagnose
      suspected neoplasias in the small pelvis by minimal invasive means, and CT-guided
      biopsy is often limited in its feasibility. The aim of our study was to evaluate
      whether transrectal ultrasound (TRUS)-guided biopsy can verify suspected
      neoplasias in the small pelvis histologically. MATERIAL AND METHODS: The study
      population consisted of 12 patients who underwent biopsy of suspected malignancy
      in the pelvis by TRUS. All patients had clinical signs of an advanced tumour
      stage and in all cases, biopsy utilising computerised tomography (CT scan) had
      been unsuccessful despite of a documented lesion on CT scan or magnetic resonance
      imaging. For the TRUS guided biopsy, a commercially available 3-dimensional 7.5
      MHz-probe was used (Combison 530 D, GENERAL ELECTRIC, Milwaukee, USA). The probe
      was armed with an 18 G biopsy gun. RESULTS: In all patients, the suspected lesion
      was easily detectable by TRUS, and tissue for verification of the malignant
      origin of the lesions could be collected under real-time TRUS with only 2
      patients needing anaesthesia. The biopsy cores were of excellent quality and
      adequate for conclusive pathological diagnosis. 6 cases of lymph node metastases
      of a transitional cell carcinoma were detected. 1 case of extended node
      metastasis in prostate cancer, 1 paravesical manifestation of recurrent cervical
      cancer, 1 metastasis of a paravesically infiltrating colon cancer and 2 cases of
      paravesical metastases of a gastric cancer were also diagnosed. In one case,
      extragenital endometriosis could be diagnosed. CONCLUSION: Based on our
      experience it can be stated that TRUS-guided biopsy is a reliable diagnostic tool
      for verification of the neoplastic origin of suspected masses in the small
      pelvis. In all cases with a history of unsuccessful CT guided biopsy, sufficient
      tissue cores for conclusive histology could be collected with our technique, and
      surgical exploration could be avoided. This technique is minimally invasive,
      without radiation exposure, well tolerated under analgesia, time efficient and
      cheap.

PMID- 17516287
TI  - Complications of double balloon enteroscopy: a multicenter survey.
AB  - BACKGROUND AND STUDY AIMS: Double balloon enteroscopy (DBE) is a new technique
      for the visualization of the small bowel. Although the technique is widely used,
      little is known about the complications. A few complications have been reported
      in the literature, mainly in case reports. The aim of this study was to establish
      the complication rate of both diagnostic and therapeutic DBE. PATIENTS AND
      METHODS: A total of 10 centers (nine academic centers and one teaching hospital)
      across four continents participated in the study. Complications were defined
      according to the literature. A therapeutic DBE was defined as a DBE with use of
      argon plasma coagulation, a polypectomy snare, injection of fluids (other than
      ink for marking), removal of foreign body, or balloon dilation. RESULTS: A total
      85 adverse events were reported in 2362 DBE procedures. In all, 40 events
      fulfilled the definition of a complication, 13 in 1728 diagnostic DBE (0.8 %) and
      27 during 634 therapeutic procedures (4.3 %). The complications were rated minor
      in 21 (0.9 %), moderate in 6 (0.3 %) and severe in 13 procedures (0.6 %). No
      fatal complications were reported. Seven cases of pancreatitis were reported, six
      after diagnostic (0.3 %) and one after therapeutic (0.2 %) DBE. CONCLUSIONS:
      Diagnostic DBE is safe with a low complication rate. The complication rate of
      therapeutic DBE is high compared with therapeutic colonoscopy. The reason for
      this is unclear. The incidence of pancreatitis after DBE is low (0.3 %), but has
      to be considered in patients with persistent abdominal complaints after a DBE
      procedure.

PMID- 17516288
TI  - Endotherapy for chronic pancreatitis with intracanalar stones.
AB  - Endotherapy for pancreatic stone is an emerging specialty. The judicious
      application of extracorporeal shock-wave lithotripsy (ESWL) and endoscopic
      retrograde cholangiopancreatography (ERCP) in selected groups of patients has
      increased the success rates of endotherapy, with excellent long-term results. In
      this review the authors share their vast experience of treating patients with
      pancreatic stones. The article will focus on the basic principles of pancreatic
      endotherapy, the instrumentation required, details of the ESWL technique and its
      applications, as well as the limitations, success rate, and complications of
      endotherapy in selected patients.

PMID- 17516289
TI  - Impact of the Leu7Pro polymorphism of preproNPY on diurnal NPY and hormone
      secretion in type 2 diabetes.
AB  - Neuropeptide Y (NPY) is a sympathetic neurotransmitter that plays a role in e.g.
      circulation, hormone release and angiogenesis. Earlier studies have shown that
      the Leucine 7 to Proline 7 (Leu7Pro) polymorphism of preproNPY is associated with
      increased risk for vascular complications in type 2 diabetes. The mechanism for
      this maybe altered transmitter and hormone levels or altered cardiovascular
      functions, which have been observed in healthy subjects having the Leu7Pro
      polymorphism. The current study was undertaken to explore if the Leu7Pro
      polymorphism has an impact on these functions in subjects with type 2 diabetes.
      Diurnal measurements were performed for Finnish Caucasian type 2 diabetes
      patients of two preproNPY genotypes (matched by sex, age, BMI, duration of
      diabetes and HbA1c) in resting position to prevent sympathetic stimulation.
      Standard meals were offered during the 24-hour study period. Nine subjects with
      the Leu7Pro polymorphism and ten subjects without this polymorphism were studied.
      Plasma concentrations of NPY, glucose, insulin, cortisol, prolactin and leptin
      were measured by taking blood samples at 20 time points (from 8 a.m. to 8 a.m.).
      Heart rate and blood pressure were measured at the same time points. The results
      show that NPY concentrations were similar in both preproNPY genotypes. Glucose,
      insulin, cortisol and leptin concentrations as well as heart rate and blood
      pressure were also similar. However, a significant difference between genotypes
      was found in the association of NPY concentrations with cortisol concentrations
      (p for difference=0.002). Also a statistically significant negative association
      of plasma NPY levels with plasma glucose levels was found in both genotypes.
      Since no impact of preproNPY genotype on mean NPY or hormone levels were detected
      in subjects with type 2 diabetes, the mechanisms for the increased risk for
      diabetic complications in the subjects with the Leu7Pro polymorphism need to be
      further explored.

PMID- 17516290
TI  - Increased serum anti-carbonic anhydrase II antibodies in patients with Graves'
      disease.
AB  - Carbonic anhydrase II (CA II) has an important role in thyroid hormone synthesis
      via regulating iodide (I-) transport across thyroidal cell membranes and the
      existence of autoantibodies against CA I and/or CA II have been shown in sera
      from patient with various autoimmune diseases such as Sjogren's Syndrome,
      Systemic Lupus Erythmatosus, type 1 diabetes, primary biliary cirrhosis and
      ulcerative colitis. The aim of this study was to investigate the presence of anti
      CA I and CA II antibodies in autoimmune thyroid disease and the relationships
      between the autoantibodies and other clinical parameters. We studied 40
      autoimmune thyroid patients (20 Hashimoto's thyroiditis, HT and 20 Graves'
      disease, GD ) and 21 healthy control subjects. Serum anti-CA I and CA II
      antibodies were screened by ELISA. Positive rate of anti-CA II (25%) antibody was
      significantly higher in GD patients as compared to HT patients and control
      subjects (p<0.05). There were no significant changes in positive rate of anti-CA
      I antibody. In addition, a significant correlation between serum anti-CA
      antibodies titers and other studied clinical parameters was not found. The
      results suggest that anti-CA II antibodies may be involved in the pathogenesis of
      GD.

PMID- 17516291
TI  - Long-term treatment of central Cushing's syndrome with rosiglitazone.
AB  - CONTEXT: Central Cushing's syndrome is not always curable by surgery or radiation
      of the pituitary. Medical treatment is often not possible or effective. Some
      studies revealed beneficial effects of the PPARgamma (Peroxisome-Proliferator
      Activator- Receptor-gamma)-agonist rosiglitazone (RG) in in vitro studies, animal
      models and short term clinical studies. OBJECTIVE: of this study was to observe
      the long-term effects of RG-treatment on cortisol- and ACTH -secretion, clinical
      outcomes and morphological changes of the pituitary in patients with persistent
      ACTH-overproduction despite previous operation and radiation. DESIGN, SETTING AND
      PATIENTS: 14 patients with persistent central ACTH -production were included and
      monitored over a period up to 12 months. RG was administered daily and increased
      to a maximum dosage of 24 mg daily, according to the response of ACTH and
      cortisol secretion. ACTH and cortisol were measured at least every 4 weeks during
      RG treatment. RESULTS: Patients were treated between 4 and 12 months with RG
      (mean 6.8 months). Compared to baseline, ACTH- and cortisol levels dropped
      significantly (p<0.01) after 12, 16, 20, 24 and 28 weeks but thereafter rose
      again during the study period, despite continuous RG- treatment and dose increase
      up to the maximum dosage. This was paralleled by reocurrence of clinical
      symptoms. MRI-scans were performed in 6 patients because of persisting visible
      adenoma, but showed no morphological changes. CONCLUSION: RG seems not to be a
      long-term treatment option for patients with persistent central ACTH-evcess.
      Though, in order to reduce perioperative complications, short term treatment of
      patients could be an alternative.

PMID- 17516292
TI  - Evaluation of biochemical hyperandrogenemia and body mass index in women
      presenting with amenorrhea.
AB  - INTRODUCTION: The aim of this study was to evaluate the correlation between
      biochemical hyperandrogenemia and body mass index in patients with amenorrhea as
      the main clinical presenting symptom. METHODS: Among 136 patients presenting with
      secondary or primary amenorrhea, hyperandrogenemia was found to be the hormonal
      cause of this specific type of irregular menses in 21 patients. A retrospective
      study was carried out to investigate the patients' serum androgen findings and
      body mass index. The ultrasound features of the ovaries were also recorded.
      RESULTS: Twenty-one of the 136 patients presenting with the most severe form of
      menstrual irregularity, amenorrhea - defined as an absence of menses for at least
      6 months - were found to have elevated serum androgen levels. The androgen
      profile included elevated levels of total testosterone (TT), or
      dehydroepiandrosterone sulfate (DHEAS), or calculated free testosterone (cFT), or
      all three, with or without an elevated luteinizing hormone-follicle-stimulating
      hormone (LH : FSH) ratio. Six patients with a body mass index > 26 kg/m2 all had
      elevated cFT, while TT was only increased in three patients. All of the patients
      had low levels of sex hormone-binding globulin (SHBG). Two patients had abnormal
      TT, cFT, and DHEAS levels together with polycystic ovaries. Eleven patients with
      a body mass index (BMI) <or=26 kg/m2 were found to have all of the combinations
      of normal and abnormal androgens. In general, cFT was significantly increased in
      patients with a BMI > 26 kg/m2 ( P<0.001), while TT serum levels did not
      significantly differ between the two groups. CONCLUSIONS: Amenorrhea is by
      definition the most severe form of menstrual disorder. Biochemical
      hyperandrogenemia can be found in a subgroup of amenorrheic patients. However,
      none of the biochemical findings of hyperandrogenemia correlated consistently
      with this specific type of menstrual disorder. In the women studied, there
      appears to be a correlation between elevated androgen levels and a BMI > 26
      kg/m2. cFT appears to be a more appropriate criterion for identifying
      hyperandrogenemia than TT in patients presenting with amenorrhea. More
      information about this condition and studies including larger numbers of patients
      are needed.

PMID- 17516293
TI  - The UCP1 gene polymorphism A-3826G in relation to DM2 and body composition in
      Czech population.
AB  - Mitochondrial uncoupling contributes to the control of energy expenditure. The
      brown fat specific uncoupling protein 1 (UCP1) mRNA was detected in
      intraperitoneal and extraperitoneal adipose tissue in adult humans. The A-3826G
      polymorphism in the UCP1 gene promoter region was found to be associated with
      reduced mRNA expression indicating that the polymorphism is of functional
      importance. OBJECTIVE: To determine allelic frequencies and genotypic
      distribution of the A-3826G polymorphism and to study its possible association
      with anthropometric parameters and biochemical markers of glucose and lipid
      metabolism in type 2 diabetes mellitus (DM2) patients (n=295), in offspring of
      DM2 patients (n=113), and in healthy adults without family history of DM2
      (n=120). RESULTS AND DISCUSSION: In the whole cohort of 528 subjects, the G
      allele was observed with a frequency of 0.26. Genotypic distribution did not
      differ between diabetics and controls. However, in the offspring of DM2 patients,
      significantly higher BMI and a trend towards higher waist to hip ratio, waist to
      height ratio, waist circumference, and subcutaneous fat mass was observed in the
      AG genotype compared with the wild-type. Similar tendency was evident in the
      control group. This indicates possible involvement of the A-3826G polymorphism in
      the regulation of body composition.

PMID- 17516294
TI  - Insulin resistance and insulin secretion in non-diabetic acromegalic patients.
AB  - Insulin resistance (IR) can be induced by high amounts of growth hormone (GH).
      AIM: To set up, in acromegaly without diabetes mellitus, a correlation between
      the disease activity in GH-secreting adenoma (AA) - assessed by minimum GH serum
      level during an oral glucose tolerance test (OGTT) - and severity of insulin
      resistance (IR), assessed by HOMA-IR index. METHODS: 75 out of 88 consecutive
      patients with acromegaly hospitalized in our department were included in this
      study. 13 patients proved to have diabetes mellitus and were excluded. Serum
      glucose, GH and insulin levels were measured by immunoradiometricassay basal and
      at 30, 60 and 120 minutes after a 75 g OGTT in 88 patients with active or cured
      acromegaly. IR was assessed using HOMA-IR index (Homa-IR=basal serum glucose
      (mg/dl) x basal serum insulin (mU/L)/22.5 x 18). A value over 2.5 was considered
      indicating IR. RESULTS: Out of 75 patients without diabetes mellitus, 36 subjects
      (48%) were presenting with IR (34 with active disease, 2 cured). We found a
      significant positive correlation (r=0.56, p<0.001) between AA and HOMA-IR. The GH
      minimal level corresponding to the intersection of the exponential regression
      curve with the HOMA-IR level of 2.5 was 8.8 ng/mL, a cut-off point indicating IR
      with 82% specificity and 78% sensitivity. The odds ratio for developing IR
      becomes significant at a minimum GH level during OGTT of 2 ng/mL (odds ratio 7.6,
      95% confidence interval 2-29). CONCLUSIONS: The severity of IR revealed by
      acromegaly correlates with GH production. A GH serum level higher than 2 ng/mL
      during OGTT indicates an increased risk for developing IR. This cut-off level of
      GH can be used as one of criteria of cured disease, regarding the lack of
      metabolic effects.

PMID- 17516295
TI  - The common C49620T polymorphism in the sulfonylurea receptor gene (ABCC8),
      pancreatic beta cell function and long-term diabetic complications in obese
      patients with long-lasting type 2 diabetes mellitus.
AB  - HYPOTHESIS: A gene polymorphism associated with accelerated beta-cell failure may
      lead to a more rapid development of long-term complications of type 2 diabetes
      (T2DM) due to a worse metabolic control of the disease. AIM OF THE STUDY:
      Evaluation of an association between the intronic C49620T (exon 16 -3c-->t)
      polymorphism in the ABCC8 (SUR1) gene and beta-cell function, as well as the
      prevalence of long-term diabetic complications in obese patients with long
      lasting type 2 diabetes. METHODS: Two hundred and fifteen obese patients with at
      least a 10-year history of T2DM were thoroughly characterized clinically. In all
      the patients the intravenous glucagon test was performed and the C49620T ABCC8
      polymorphism was assessed. Subgroups of patients, classified either according to
      genotype or to allele carriage, were compared. RESULTS: No difference was found
      between the groups in variables describing beta-cell function and the prevalence
      of chronic diabetic complications, with the exception of a significantly lower
      incidence of brain stroke in CC homozygotes than in patients carrying T allele
      (CT+TT). Body mass index was higher in patients carrying C allele than in TT
      homozygotes. HDL-cholesterol was higher in CT heterozygous than in homozygous CC
      or TT patients. CONCLUSIONS: There is no association between the ABCC8
      polymorphism gene and the beta-cell function or the prevalence of chronic
      diabetic complications in obese patients with long-term T2DM, except for brain
      stroke. The results might suggest that the homozygous CC subjects are at lower
      risk of the complication, but additional studies are warranted to test this
      finding.

PMID- 17516296
TI  - TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and
      macrovascular complications in diabetic patients on aspirin.
AB  - BACKGROUND: Tumor necrosis factor (TNF)-alpha has pleiotropic effects in cytokine
      mediated inflammation underlying atherogenesis. Activation of this inflammatory
      process is assumed to be different in diabetic and non-diabetic individuals.
      Previous studies in non-diabetic subjects showed no association between TNF-alpha
      -308G>A polymorphism and coronary artery disease. METHODS: Vascular complications
      and cytokine serum concentrations were assessed as a function of the TNF-alpha 
      308G>A polymorphism in 76 diabetic patients on low-dose aspirin. RESULTS: Of 76
      adult diabetic patients, 18 (24%) carried the TNF-alpha -308A allele (17 AG, 1
      AA) and 58 (76%) carried wild-type alleles (GG). Prevalence of macrovascular
      complications was 33% in TNF-alpha -308A allele carriers (AG+AA) and 78% in wild
      type allele carriers (GG) (p<0.001). In contrast, prevalence of microvascular
      complications was 78% and 84%, respectively, and did not significantly differ
      between the study groups. TNF-alpha -308A allele carriers (AG+AA) compared to
      wild-type allele carriers (GG) had significantly lower median serum
      concentrations of hs-C-reactive protein (1.5 vs 2.9 mg/L, p=0.030), interleukin 1
      beta (0.9 vs 1.2 ng/L, p=0.046), and interleukin-6 (3.6 vs 4.9 ng/L, p=0.023). In
      multiple regression analysis, the prevalence of macrovascular diabetic
      complications was significantly associated with TNF-alpha -308G>A polymorphism
      (p<0.001) and serum concentrations of HDL-cholesterol (p=0.007) while confounding
      effects of further variables were excluded. CONCLUSION: TNF-alpha -308G>A
      polymorphism modulates cytokine serum concentrations and macrovascular
      complications in diabetic patients on aspirin. Diabetic carriers of the TNF-alpha
      -308A allele might benefit more from a prophylaxis with low dose aspirin than non
      carriers.

PMID- 17516297
TI  - An insertion/deletion polymorphism in the alpha2B adrenoceptor gene is associated
      with peripheral neuropathy in patients with type 2 diabetes mellitus.
AB  - Alpha2B adrenoceptor (alpha2B-AR) mediates a variety of functions in humans. An
      insertion/deletion (I/D) polymorphism of the alpha2B-AR gene located on
      chromosome 2 has been described. The aim of the present study was to investigate
      the potential association between alpha2B gene I/D polymorphism and peripheral
      neuropathy in Greek patients with type 2 diabetes mellitus. The study included
      130 patients (70 men) with diabetic neuropathy (group A) and 60 patients (34 men)
      without diabetic neuropathy (group B). There was no difference in age, gender and
      diabetes duration between the groups. Diabetic neuropathy was diagnosed by
      clinical examination using the Diabetic Neuropathy Index (DNI). Genotyping of I/D
      polymorphism was performed by PCR. Frequency of the D allele was significantly
      higher (p=0.001) in group A (26.9%) as compared to group B (11.7%). DNI score
      differed significantly (p=0.001) between the three genotype groups (I/I, I/D,
      D/D). It was significantly higher (p=0.04) in patients with I/D (3.7+/-1) than in
      those with I/I (2.5+/-0.9) and significantly higher (p=0.001) in patients with
      D/D (5.6+/-1.3) than in those with I/D (3.7+/-1). CONCLUSIONS: Patients with
      neuropathy exhibit a significantly higher frequency of the D allele in comparison
      to those without neuropathy. Presence of the D allele is also associated with a
      higher neuropathic score. These results provide evidence for an association of
      the D allele with both presence and severity of neuropathy in patients with type
      2 diabetes mellitus.

PMID- 17516298
TI  - Hyperthyroidism with fibrous dysplasia: an unusual presentation of McCune
      Albright syndrome.
AB  - McCune-Albright Syndrome (MAS) is a sporadic disorder characterized by a triad of
      poly/monostotic fibrous dysplasia, cafe-au-lait macules, and hyperfunctioning
      endocrinopathies. Hyperthyroidism as a manifestation of endocrine hyperfunction
      in MAS is uncommon. We report a patient who had polyostotic fibrous dysplasia
      with multiple pathological fractures and hyperthyroidism. She underwent surgery
      for hyperthyroidism and received pamidronate therapy with remarkable relief in
      bone pains and without any new fractures during her subsequent follow up of 3
      years.

PMID- 17516299
TI  - Severe cognitive dysfunction in a patient with polyendocrinopathy.
AB  - BACKGROUND: Polyglandular Autoimmune syndromes (PGAs) or polyendocrinopathies are
      immune mediated multiple endocrine gland failure sometimes accompanied by
      nonendocrine autoimmune disorders with varieties of presentations. CASE REPORT:
      We describe a case of a middle aged man with severe cognitive dysfunction, brain
      atrophy, adrenal insufficiency, hypothyroidism, renal failure, thrombocytopenia,
      and positive antiphospholipid antibodies, with significant renal and cognitive
      improvement after hormone replacement. CONCLUSIONS: PGAs may present with a broad
      spectrum of manifestations related to different organs like nervous,renal,cardiac
      and hematopoietic systems, sometimes challenging both to physician and the
      patient.

PMID- 17516300
TI  - Is basal insulin always the first choice for initiation of insulin therapy in
      type 2 diabetic patients?

PMID- 17516301
TI  - [Why the delivery room is not called the delivery room].

PMID- 17516302
TI  - [Combined spinal-epidural anaesthesia for pain relief in obstetric patients].
AB  - Besides epidural analgesia combined spinal-epidural anaesthesia (CSE) is one of
      the favourite techniques of regional anaesthesia for pain relief in obstetric
      patients. CSE combines the advantage of spinal anaesthesia, e.g. rapid onset and
      reliable effect, with the advantage of continuous epidural anaesthesia, e.g.
      titration of analgesics and prolongation. While subarachnoid injection of solely
      opioids provides fast pain relief for nearly 2 hrs in the first stage of labour
      with an opportunity of ambulation for the parturient ("walking epidural"), the
      subarachnoid injection of a combination of low doses of opoids and local
      anaesthetics provides profound analgesia with minor motor blocking side effects
      for 1-2 hrs in the second stage of labour.

PMID- 17516303
TI  - [Walking epidurals: mobilisation during neuraxial labour analgesia].
AB  - Neuraxial anaesthesia offers the most effective form of obstetric pain relief and
      is superior to other methods of analgesia, and it does not increase the risk of
      caesarean section. In daily practice, various techniques are used including the
      options of patient-controlled epidural analgesia (PCEA) and combined spinal
      epidural analgesia (CSEA). Risk information is one of the prerequisites for
      'informed consent'. Omitting the epidural test dose and using low-dose local
      anaesthetics with lipophilic opioids enhances early mobilisation.

PMID- 17516304
TI  - [Successful use of an AED following anterior myocardial infarction].
AB  - A participant of the annual Hamburg marathon collapses on the finish line. Medics
      at the scene find a conscious patient and prepare transport to the finish area
      medical center. During transport the patient becomes unconscious and pulseless.
      The medics immediately perform basic life support and cardiopulmonary
      resuscitation (CPR). An automated external defibrillator (AED) is attached and
      after analysis of the patient}s heart rhythm the patient is defibrillated twice.
      The ambulance service reach the scene with a delay. The emergency physician}s ECG
      shows ventricular fibrillation (VF) and two more defibrillations are delivered.
      Return of spontaneous circulation can be achieved. After stabilisation the
      patient is taken to hospital by ambulance. The ECG shows an anterior myocardial
      infarction and right bundle-branch block. The coronary angioplasty (PTCA) shows
      single-vessel disease with complete stenosis of the proximal part of the anterior
      interventricular branch. Revasucarisation is successful and a coronary stent is
      applied. The patient survives neurologically intact. This case report
      demonstrates the importance of readily available AED and specially trained
      medics. By immediately using the AED this patient was defibrillated before the
      ambulance service and emergency physician arrived at the scene. Spontaneous
      circulation was restored.

PMID- 17516305
TI  - [Management of respiratory complications].

PMID- 17516306
TI  - [Anesthesia and restrictive and obstructive pulmonary diseases].
AB  - Restrictive and obstructive pulmonary diseases are major risk factors of
      perioperative morbidity and mortality. The incidence of pulmonary complications
      may be in the range of 3 and 40% (3), depending on the underlying disease and the
      type of surgery. In this review the specific pathophysiology, preoperative
      evaluation and suitable anesthesia procedures are discussed for patients with
      restrictive and obstructive pulmonary diseases.

PMID- 17516307
TI  - Immediate versus delayed umbilical cord clamping in premature neonates born < 35
      weeks: a prospective, randomized, controlled study.
AB  - The purpose of this study was to test whether delayed versus immediate cord
      clamping would result in higher blood pressure (BP) and hematocrit (Hct), and to
      assess its clinical effects on the neonatal course in premature neonates (< 35
      weeks). This was a prospective, masked, randomized, controlled study. Prior to
      delivery, 35 neonates were randomly assigned to immediate cord clamping (ICC) at
      5 to 10 seconds, and a comparable group of 30 neonates were randomly assigned to
      delayed cord clamping (DCC) at 30 to 45 seconds. Intention-to-treat analyses
      revealed that the DCC group tended to have higher initial diastolic BP and higher
      Hct (especially in vaginally delivered neonates). Infants weighing < 1500 g with
      DCC tended to have higher mean BP, and needed less mechanical ventilation and
      surfactant compared with ICC neonates. Infants with DCC did not experience more
      polycythemia (Hct > 60%), but had a trend toward higher bilirubin levels with no
      differences in the phototherapy needs. DCC seems to be safe and may be beneficial
      when compared with ICC in premature neonates. However, the differences between
      the two methods were modest and the clinical relevance needs to be assessed
      further by larger studies and additional meta-analysis of randomized trials.

PMID- 17516308
TI  - A novel tocolytic agent: effects of letrozole on gestational length and
      parturition time.
AB  - The purpose of this study was to determine whether letrozole, a potent aromatase
      inhibitor, could prolong gestation and/or delay parturition in rats. Seventy-five
      rats were divided into five groups of 15 rats each. Group I and group II rats
      were administered letrozole orally at doses of 0.002 and 0.02 mg/kg/day from days
      15 through 21 of pregnancy, respectively. Rats in group IA were administered a
      concomitant estradiol cyclopentylpropionate (ECP) injection on day 15 and 0.002
      mg/kg letrozole in that same manner as for group I. Rats in group IIA were
      administered concomitant ECP on day 15 and 0.02 mg/kg letrozole in the same
      manner as for group II. The control group received sterile saline only. Study and
      control groups were compared with respect to gestational length, parturition
      time, fetal mortality rate, stillbirth rate, and fetal body weight. Oral
      administration of letrozole both at daily doses of 0.002 mg/kg/day (group I) and
      0.02 mg/kg/day (group II) consistently prolonged gestation and parturition time.
      The values of stillbirth rate, fetal mortality rate, and fetal body weight of
      group I were similar to those in the control group; conversely, fetal mortality
      rate and stillbirth rate of group II were higher than those values in the control
      group, and fetal body weight of group II was lower than in the control group. It
      was observed that concomitant injection of ECP effectively reversed the
      deleterious effects of letrozole on gestational length, parturition time, fetal
      mortality rate, stillbirth rate, and fetal body weight. The results of this study
      indicate that the aromatase inhibitor letrozole can prolong gestation and delays
      parturition in rats. Its deleterious effects on parturition can be reversed by
      ECP injection.

PMID- 17516309
TI  - Premature infants: analysis of serum phosphate during the first 4 weeks of life.
AB  - The purpose of this study was to establish phosphate norms for the first 4 weeks
      of life for neonates with birthweight (BW) 500 to 1500 g. The study group
      included 52 consecutively born neonates: group A (n = 24; BW 500 to 1000 g), and
      group B (n = 28; BW 1001 to 1500 g). Phosphate levels are reported daily (days 1
      to 5), and then weekly until week 4. Except for the first 2 days of life,
      phosphate levels were statistically lower in group A versus group B. A
      prospective study is required to examine whether phosphate levels can be used as
      a marker of acuity in neonates and to examine the effect of phosphate repletion
      on metabolic functions.

PMID- 17516310
TI  - Intrapartum predictors of uterine rupture.
AB  - This case-controlled study reviewed 26 cases of uterine rupture at an academic
      medical center. Controls were selected in a 2:1 design by reviewing the immediate
      successful vaginal birth after cesarean delivery (VBAC) before and after each
      case of uterine rupture. At less than 2 hours before delivery or acute uterine
      rupture, mild and severe variable decelerations, persistent abdominal pain, and
      hyperstimulation were more common in cases of uterine rupture as compared to
      controls and had statistically significant positive likelihood ratios (LR). Mild
      and severe variable fetal heart rate decelerations, especially in the presence of
      persistent abdominal pain, may predict uterine rupture in patients attempting
      VBAC.

PMID- 17516311
TI  - [Surgical treatment of esophageal tumors including local ablation].

PMID- 17516312
TI  - [Quality indicators for diagnostic and therapy of rectal carcinoma].
AB  - Diagnostic and treatment of rectal cancer need a continuous quality assessment.
      Indicators of quality were compiled as indicator profile for a summarizing
      evaluation. The indicators selected should potentially show an appreciable
      variation of the quality target and in addition should be decisive for the
      outcome. For the evaluation of the clinical diagnostic the frequency of the
      determination of the pretherapeutic T, N and M categories and the proportion of
      pT 1-tumors were chosen, for the pathological diagnostic the number of
      histologically examined lymph nodes and the proportion of lymphnode positive
      patients. Process quality of treatment was defined by the following indicators:
      proportion of tumor excision, of definite therapy by local tumor removal, of neo
      adjuvant long-term radiochemotherapy, of adjuvant treatment in patients not
      selected for neoadjuvant therapy, of total / partial mesorectal excision, of
      abdomino-perineal resection, postoperative mortality, frequency of clinically
      apparent anastomotic leakage, and of neurogenic bladder dysfunction at hospital
      discharge. The indicators for the quality of the performance of treatment were
      differentiated between surrogate indicators that can be determined immediately
      after accomplishment of primary surgical therapy giving strong clues for the
      further course of disease at an early date, and definite indicators. Important
      surrogate indicators comprise the occurrence of intraoperative local tumor cell
      dissemination, R 1 / 2-resection, pathohistologically CRM-positive tumor
      resection, and the quality of mesorectal excision (proportion of incomplete
      mesorectal excision). The definite indicators include the 5-year local recurrence
      rate and the 5-year overall survival rate. The corresponding quantifying
      parameters for the individual indicators are specified in this paper with precise
      figures.

PMID- 17516313
TI  - [Report on the workshop "workflow rectal cancer II" in Burghausen].
AB  - The task force "workflow rectal cancer II" defined operative techniques in lower
      rectal cancer, especially the total mesorectal excision and an improved technique
      of abdominalperineal resection. New aspects for treatment of rectal cancer with
      primary distant metastases are described. Due to newer publications a concept of
      bidirectional procedure with surgery and radiochemotherapy is recommended, where
      the operation must not be inevitably the first step. In anastomoses below 6 cm of
      the anocutaneous verge a reservoir should be performed on principle due to better
      functional results. The colon-j-pouch with a maximal loop length of 6 cm is best
      investigated under these conditions, the other procedures should be further
      evaluated.

PMID- 17516314
TI  - [Progress report about the 1st Workshop on Local Excision of Rectal Cancer].
AB  - To determine the significance of local excision (LE) of rectal cancer and discuss
      oncologic results, a 1st Workshop on LE of rectal cancer was held at the
      Department of General und Abdominal Surgery, Johannes Gutenberg-University Mainz,
      Germany. The option of broadening the indication for local excision after
      neoadjuvant radiochemotherapy (nRCT) of rectal cancer was to be assessed. Local
      excision of "low risk" T 1 carcinomas was rated as oncologically adequate therapy
      with good functional results and low complication rates. Transanal endoscopic
      microsurgical (TEM) resection was the preferrred technique. Pre-requisite for the
      achievement of low recurrence rates (5 %) is an R0 resection with a safety margin
      of at least 1 mm (R < or = 1 mm) without tumor fragmentation, because otherwise
      possible tumor cell displacement and RX resection may not allow an assessment of
      the resection margin. "high risk" tumors or T 2 carcinomas were not considered an
      indication for local excision. To identify additional histological risk factors
      for the oncological outcome (sm-level, tumor budding, mucinous component,
      perineural infiltration, etc.) the initiation of a multi-center register study
      (LERC = local excision of rectal cancer) was suggested and is now in preparation.
      If the finding after TEM resection is not a "low risk" T 1 carcinoma, but a "high
      risk" situation or a T 2 tumor, immediate reoperation is advised resulting in
      similar outcomes as compared to primary conventional surgery. A literature
      analysis of LE after neoadjuvant RCT of T 2/3 rectal cancers showed a local
      recurrence rate of 0 % for ypT 0 and of 5 % for ypT 1 findings (studies with
      small patient collectives and short follow-up periods). The lymph node status of
      T 2 / 3 carcinomas after nRCT is unclear. More advanced/primary not resectable
      tumors (T 3 / 4) showed lymph node metastases in 5 % for ypT 0 and in 12 % for
      ypT 1 findings after nRCT, suggesting that for earlier T categories lower rates
      can be expected. On the basis of these favourable results a prospective multi
      center study will be initiated. A study protocol will be established during the
      2nd Workshop on LE of rectal cancer in Mainz.

PMID- 17516315
TI  - [Economic observations on the operative treatment of acute appendicitis].
AB  - The costs of the operative treatment of acute appendicitis have to be verified
      under DRG conditions. Laparoscopic and open appendectomies in a 5-year-period
      were evaluated retrospectively. Analyses of costs of the year 2004 were performed
      according to the clinical automatic settlement (SAP / R3) in direct comparison to
      the data of 140 participating hospitals using the same software. In the 5-year
      period 775 of 830 (91.8 %) appendectomies were started laparoscopically, in 68
      cases the method was converted to the open surgical procedure. Postoperative
      complications required radiologic interventional treatment or reoperation in 4.2
      % of the patients. The arising costs in the own hospital and the 140 associated
      hospitals were defrayed only for 90 % by the DRG-payment system. The deficit for
      the DRG codes G 23 Z, G 22 Z and G 07 Z were 212 euro, 296 euro and 455 euro per
      case. Compensation of costs in clinical routine results from reduction of
      duration of patients stay (162 euro per day) or avoidance of the laparoscopic
      procedure. The material costs of laparoscopic appendectomy are 4.3 times higher
      than the costs of the open conventional procedure (310 euro vs. 71 euro). The
      clinical costs of appendectomy are not compensated by the DRG-System. The surgeon
      has to take into account the economic aspects of the intended operative
      procedure.

PMID- 17516316
TI  - [Laparoscopic appendectomy in pregnancy].
AB  - BACKGROUND: Acute appendicitis is the most common cause of an acute abdomen in
      pregnancy. However, due to the potential fetal risk associated with the CO2
      pneumoperitoneum and various operative technical reasons there is still
      controversy about the role of laparoscopic appendectomy in pregnant women.
      PATIENTS AND METHODS: Between January 2000 and November 2005, 283 women between
      17 and 45 years with suspected appendicitis underwent laparoscopic appendectomy
      at our institution. Fifteen of these patients (5.3 %) were pregnant at the time
      of surgery (mean age, 28 years; range, 18-40 years; mean gestational age, 21.9
      weeks; range, 14-34 weeks). Perioperative obstetric monitoring included fetal
      ultrasound, including Doppler sonography and cardiotocography. Clinical data were
      collected prospectively. Complete follow-up data were available in 14 patients.
      RESULTS: All 15 patients underwent successful laparoscopic appendectomy. Mean
      operation time was 53 minutes (range, 30-100 minutes). The histologic
      appendicitis / appendectomy ratio was 73 %. One patient showed a postoperative
      pyelonephritis, another a cystitis. Average length of hospital stay was 5.5 days
      (range, 3-10 days). All fourteen pregnancies with complete follow-up resulted in
      delivery of healthy infants. The mean gestational age at delivery was 39.6 weeks
      (range, 35-42 weeks). Two patients (14.3 %) had a preterm delivery at 35 weeks
      with uncomplicated outcome. One patient underwent caesarean section at 41 weeks
      after chorioamnionitis. CONCLUSIONS: Laparoscopic appendectomy is a safe and
      effective method to treat acute appendicitis in pregnant women regardless of the
      trimester. For the best outcome the operation should be performed in a center
      where surgeons, perinatologist, obstetricians and anesthesiologists work together
      as a part of an interdisciplinary team.

PMID- 17516317
TI  - [Diagnosis of appendicitis using harmonic ultrasound imaging].
AB  - INTRODUCTION: Harmonic Imaging (HI) is a new Ultrasound (US) modality with high
      contrast and spatial resolution. Aim of this study was to compare fundamental
      imaging (FI) and HI in the diagnosis of appendicitis. PATIENTS AND METHODS: In 50
      children (male : female, 25 : 25; mean age: 9.9 years) prior to an appendectomy
      US of the right lower quadrant was performed in both FI and HI (Tissue Harmonic
      Imaging - THI - Sonoline Elegra, Siemens, 7.5 MHz linear). The images were
      compared with respect to delineation of surrounding, contour, wall and content of
      the appendix. RESULTS: In 43 / 50 (86 %) patients diagnosis of appendicitis was
      confirmed histologically (sensitivity 98 %, specificity 94 %). In 37 / 43
      patients the appendix was depicted using FI. With HI this number was 40 / 43. HI
      was significantly better in delineating the contour, wall, mucosa and content of
      the appendix (p < 0.01). HI also exceeded in demonstrating free fluid,
      mesenterial lymph nodes and surrounding echogenicity. CONCLUSION: HI of
      appendicitis provides images with significantly better quality than FI. When both
      imaging options are available harmonic imaging modality should be the preferred
      choice for scanning the appendix.

PMID- 17516318
TI  - [Community MRSA].
AB  - Additional to epidemic methicillin resistant Staphylococcus aureus (haMRSA) which
      had been disseminated in and between hospitals, MRSA emerged in the community
      independent upon the nosocomial setting (caMRSA). caMRSA possess the capacity to
      form Panton-Valentine-Leukocidin (PVL) as a special virulence factor. In general
      PVL-positive S. aureus isolates are associated with necrotizing skin and soft
      tissue infections as well as with necrotizing pneumonia. caMRSA are less "broad"
      resistant against different groups of antibiotics as haMRSA and require special
      attention when performing antimicrobial susceptibility testing. Prevention of
      further dissemination of caMRSA requires appropriate diagnosis, therapy and
      sanitation of the carrier state. Hygienic measures have not only to be taken in
      ambulant treatment but also in households of affected patients.

PMID- 17516319
TI  - [Peritonitis: main reason of severe sepsis in surgical intensive care].
AB  - INTRODUCTION: Aim of the study was to determine the epidemiology of sepsis in an
      university surgical intensive care unit. We were mainly interested in getting
      information about incidence, reason and clinical course of peritonitis. The
      results should give more information about diagnostic and therapy of sepsis in
      the surgical intensive care. METHODS: We analyzed our 2 676 ICU-patients from
      2000 to 2002 with infection as main diagnosis. By means of medical report we
      analyzed the kind of infection and the clinical course of 561 (21 %) patients.
      For 356 (13.3 %) patients with peritonitis we observed the kind, the reason and
      the severity of infection and further the special events in the clinical course.
      RESULTS: The incidence of severe sepsis was 14.8 %. With 63 % the peritonitis is
      the main infectiological diagnosis on admission to ICU. 33.8 % of infections are
      hospital acquired. 71.3 % of patients with peritonitis developed a severe sepsis
      or septic shock during the clinical course. On average 4.7 further abdominal
      surgical interventions and 5.1 new occurring nosocomial infections marked a
      difficult surgical and infectious treatment course. Hospital acquired infections
      (70 %), high value of scoring and inadequate surgical treatment (23.7 %) have
      proved to be a good prognostic instrument for the development of tertiary
      peritonitis. With a share of 17 % from patients with peritonitis and a mortality
      of 35 % they have a strong influence on the ICU-mortality. CONCLUSION:
      Peritonitis is the main reason of severe sepsis on the surgical ICU. Hospital
      acquired infections especially the tertiary peritonitis have the highest
      mortality. High mortality is the consequence from the large number of difficult
      clinical courses and high rates of severe sepsis and septic shock. "Second hits"
      play a crucial role for the therapy and the prognosis of these patients. To
      decline the mortality future studies must more consider the problem of hospital
      acquired and tertiary abdominal infections.

PMID- 17516320
TI  - [Vacuum assisted closure therapy for the treatment of sternal wound infections
      after heart transplantation: preliminary results].
AB  - Sternal wound infection after heart transplantation is a feared and potentially
      life threatening complication with reported incidences between 2.5 % and 3.6 %.
      However, optimal therapy of sternal wound infections in heart transplant
      recipients remains a matter of controversy, particularly the effect of
      immunosuppression in those patients is still unclear. We examined 5 heart
      transplanted patients (4 men and 1 woman with a median age of 46 +/- 21.4 years
      (ranging from 14 to 59 years) in terms of inflammation and treatment response
      during VAC therapy. Infection begin was median 18.2 days (+/- 10 days, ranging
      from 5 to 28 days) after transplantation. VAC therapy lasted on average 12.2 +/-
      2 days, ranging from 10 to 19 days. A median of 3 changes (range from 3 to 5)
      were necessary until the definitive closure. We examined C-reactive protein,
      leucocyte count and fibrinogen 2 days pre VAC, during VAC treatment and 2 days
      after definitive closure. All five patients showed an increase of leucocytes at
      every VAC change. Furthermore, we saw an adequate reaction to the VAC in terms of
      granulation tissue growth and resolution of infection. Transplanted patients had
      an increase of leucocytes at every VAC change. Furthermore all patients showed an
      adequate response of VAC treatment in terms of granulation tissue in growth and
      infection decline. Therefore a reduction of immunosuppressive therapy is not
      necessary, which in turn would increase the risk of rejection.

PMID- 17516321
TI  - [Tree collisions in road traffic accidents - mechanism and pattern of injury].
AB  - INTRODUCTION: In Germany, the county of Mecklenburg-Vorpommern has got the
      highest frequency of traffic accidents. 42 % of all deadly injured car accident
      victims in Mecklenburg-Vorpommern sustained a tree collision. Aim of this study
      was to analyze tree collisions regarding typical pattern and severity of injury.
      METHODS: During an on-going prospective, non-interventional accident survey
      within a defined area of the county of Mecklenburg-Vorpommern tree collisions
      with minimum one victim sustaining a Maximum Abbreviated Injury Scale of 1-6
      injury were analyzed. RESULTS: In between January 2001 and June 2004 287
      accidents were documented. 19 % (54) were tree collisions. 81 % of drivers were
      male. 36 of 54 tree collisions (67 %) occurred on straight roadways. The mean ISS
      was 31.3 (SD +/- 29.8), 30 % (23) of the passengers died. 70 of 78 individuals
      sustained more than one injury. With that, the combination of head- and chest
      trauma was most frequent and associated with the highest injury severity.
      DISCUSSION: Especially tree collisions lead to severe trauma. Interestingly, most
      accidents did occur on straight roadways.

PMID- 17516322
TI  - [Long-term results of salvage procedures following intrapelvic migration of
      loosened total hip arthroplasties].
AB  - INTRODUCTION: Intrapelvic migrations of loosened total hip arthroplasties are
      rare. Primary objective of revision arthroplasty in these cases is the
      reconstruction of acetabular defects for example by acetabular reinforcement
      rings. Presenting 3 cases the possibilities and long-term results of Girdlestone
      situations or arthrodesis of the hip following intrapelvic migration of a total
      hip arthroplasty are described. PATIENTS AND METHODS: A Girdlestone procedure was
      performed in a 62-year-old female patient due to intrapelvic migration of a
      threaded cup and development of a false aneurysm of the iliac artery. 15 years
      later the patient was out of any complaints. In another patient an arthrodesis of
      the hip due to destruction of the acetabulum and central migration of a
      hemiprosthesis was performed. 15 years later, too, this patient was out of any
      complaints. In a third patient with a contralateral preexisting Girdlestone hip
      an arthrodesis of the hip due to excessive loosening and severe acetabular
      defects of a cemented total hip arthroplasty was performed on the other side. 13
      years later both hips were stiff, nevertheless the patient was satisfied.
      CONCLUSION: Presenting these cases we come to the conclusion that even now a
      Girdlestone operation or an arthrodesis of the hip should be taken into account
      if reconstruction of acetabular defects is no more feasible. The long-term
      results are satisfactory.

PMID- 17516323
TI  - [Restoration of the continuity of the colon with preservation of an existing
      colostomy].
AB  - A new technique for the restoration of the continuity of the colon with
      preservation of an existing colostomy is described here. A 75-year-old male with
      a three-year history of abdominal-perineal resection and a well functioning end
      colostomy was admitted to our department for a second primary cancer of the
      descending colon. At operation the colon was divided close to the abdominal wall;
      the colostomy was left in situ while the descending colon and mesocolon were
      radically resected. The viability of the colostomy was being continuously
      inspected. An EEA stapler was then inserted through the colostomy and an
      anastomosis was created. Shortening the length of the operation and avoiding the
      possible complications that follow the creation of a new stoma are the major
      benefits of the technique. Still, the viability of the colostomy after its
      separation of the rest of the colon and mesocolon has to be ensured before
      proceeding.

PMID- 17516324
TI  - Mediastinal necrosis in acute pancreatitis - case report.
AB  - Ascites, pseudocyst, necrosis of the retroperitoneal fat tissue and
      pancreatopleural fistula with left sided pleural effusion may complicate
      pancreatitis. However, steatonecrosis of the mediastinum and right side pleural
      effusion are rather rare complications of pancreatitis. We present a case of a
      patient with alcohol induced pancreatitis. Chest x-ray showed right sided pleural
      effusion. Although high levels of amylase in pleural fluid made the diagnosis of
      pancreatopleural fistula most likely, necrosis of the mediastinal fat tissue with
      right side pleural effusion was found postmortem.

PMID- 17516325
TI  - [A rare splenic involvement by Echinococcus multilocularis - case report].
AB  - In the present case an 81-year-old patient was operated upon for a suspected
      atraumatic spleen rupture. During the operation a spleen abscess was found.
      Histological examination of the removed spleen revealed an Echinococcus
      multilocularis infection. There was no sign of further organ involvement:
      surprisingly the liver was not affected. Case history, clinical outcome and the
      prescribed treatment are described. A short overview of the Echinococchus
      multilocularis syndrome is presented.

PMID- 17516326
TI  - [Hormone inactive parathyroid cyst: rare differential diagnosis in the evaluation
      of cervical cysts].
AB  - Parathyroid cysts are a very rare disease entity. Hormone activity is uncommon
      and they usually present without any clinical symptoms. The differential
      diagnosis of cystic neck masses should nevertheless include parathyroid cysts as
      surgical therapy can be very effective. We report the case of a 57-year-old
      patient presenting to our department with a hormone inactive parathyroid cyst.
      Final diagnosis was achieved eventually after histological examination of the
      resected specimen, which is the reason for evaluating the current data for
      preoperative management of this disease entity in this case report.

PMID- 17516327
TI  - New weakly cytotoxic eremophilane sesquiterpenes from the roots of Ligularia
      virgaurea.
AB  - Six new eremophilane sesquiterpenes, including a novel nortrieremophilane carbon
      skeleton, were isolated from the roots of Ligularia virgaurea. Their structures
      were elucidated as 3 alpha,4 alpha-epoxy-6 alpha-(2'-methylacryloyl)oxy-8 alpha
      methoxyeremophil-7(11)-en-8 beta,12-olide (1), 3 alpha,4 alpha-epoxy-6 alpha-(2'
      methylacryloyl)oxy-8 alpha-ethoxyeremophil-7(11)-en-8 beta,12-olide (2), 1
      beta,10 beta-epoxy-6 beta-(2'-methylacryloyl)oxy-8 beta-methoxyeremophil-7(11)-en
      8 alpha,12-olide (3), 1 beta,10 beta-epoxy-6 beta-angeloyloxy-8 beta
      methoxyeremophil-7(11)-en-8 alpha,12-olide (4), 6 beta-methoxyeremophil-7(11)-en
      8 beta,12-olide (5), and 5 beta-angeloyloxy-3a,4,5,6,7,7a-hexahydro-3a beta
      methyl-1 H-indene-2,4 beta-dioic acid methyl ester (6) by spectral methods,
      including IR, HR-ESI-MS, 1D and 2D NMR techniques. All of compounds were
      evaluated for their in vitro cytotoxic activities against human hepatoma (SMMC
      7721), human promyelocytic leukemia (HL-60), and human hepatocyte (L-02) cells.

PMID- 17516328
TI  - Enhancement of cardenolide and phytosterol levels by expression of an N
      terminally truncated 3-hydroxy-3-methylglutaryl CoA reductase in Transgenic
      digitalis minor.
AB  - Pathway engineering in medicinal plants attains a special significance in
      Digitalis species, the main industrial source of cardiac glycosides, steroidal
      metabolites derived from mevalonic acid via the triterpenoid pathway. In this
      work, the Arabidopsis thaliana HMG1 cDNA, coding the catalytic domain of 3
      hydroxy-3-methylglutaryl CoA reductase (HMGR1S), a key enzyme of the MVA pathway,
      was expressed in the cardenolide-producing plant Digitalis minor. Transgenic
      plants were morphologically indistinguishable from control wild plants and
      displayed the same developmental pattern. Constitutive expression of HMG1
      resulted in an increased sterol and cardenolide production in both in vitro- and
      greenhouse-grown plants. This work demonstrates that transgenic D. minor plants
      are a valuable system to study and achieve metabolic engineering of the
      cardenolide pathway and in consequence for the genetic improvement of Digitalis
      species.

PMID- 17516329
TI  - New dihydrochalcones and anti-platelet aggregation constituents from the leaves
      of Muntingia calabura.
AB  - Two new dihydrochalcones, 2,3-dihydroxy-4,3',4',5'-tetramethoxydihydrochalcone
      (1) and 4,2',4'-trihydroxy-3'-methoxydihydrochalcone (2), and a new flavanone,
      (2R,3R)-(-)-3,5-dihydroxy-6,7-dimethoxyflavanone (3), together with nineteen
      known compounds have been isolated from the leaves of Muntingia calabura. The
      structures of three new compounds were determined through spectral analyses
      including extensive 2D-NMR data. Among the isolates, 2,3-dihydroxy-4,3',4',5'
      tetramethoxydihydrochalcone, 5,7-dihydroxy-3-methoxyflavone, 5,7-dihydroxy-6
      methoxyflavone, 5,4'-dihydroxy-3,7-dimethoxyflavone, (2S)-7,8,3',4',5'
      pentamethoxyflavan, (2S)-5'-hydroxy-7,8,3',4'-tetramethoxyflavan, and methyl
      gallate exhibited significant anti-platelet aggregation activity in vitro.

PMID- 17516330
TI  - Molecular authentication of the traditional dai medicinal plant Croton caudatus.
AB  - Croton caudatus is an important species in Dai folk medicine. Some other Croton
      species, in particular, C. kongensis, C. cascarilloides, C. crassifolius, C.
      lachnocarpus and C. olivaceus are often marketed as C. caudatus, and thus, the
      therapeutic effects of C. caudatus are not achieved. The respective morphological
      features of the plants are similar, and they are not easy to distinguish
      morphologically from each other. In an attempt to find a method for
      discriminating among these species, we compared their nuclear ribosomal DNA
      internal transcribed spacer (ITS) region. Species-specific probes were derived
      from the ITS region of these species for species identification. This method
      provides effective and accurate identification of C. caudatus.

PMID- 17516331
TI  - Antimicrobial activity of seven hypericum entities from central Italy.
AB  - Methanol-acetone extracts from aerial parts of seven entities of the genus
      Hypericum [H. perforatum L. subsp. perforatum, H. perforatum L. subsp. veronense
      (Schrank) Ces., H. montanum L., H. hyssopifolium Chaix, H. hirsutum L., H.
      hircinum L. subsp. majus (Aiton) N. Robson, H. tetrapterum Fr.] growing in the
      Appennino Umbro-Marchigiano (central Italy) were tested in vitro for their
      antimicrobial activity against two Gram-positive bacteria (Staphylococcus aureus
      and Enterococcus faecalis), two Gram-negative bacteria (Escherichia coli and
      Pseudomonas aeruginosa) and the yeast Candida albicans, by the Kirby-Bauer agar
      diffusion method. The two H. perforatum subspecies were particularly active
      against Gram-positive and Gram-negative bacteria, supporting the use of these
      plants in the traditional medicine of central Italy to treat wounds, skin and
      infectious diseases. However significant values of inhibition were given also by
      H. hirsutum against S. aureus and P. aeruginosa, and by H. hyssopifolium, H.
      hircinum subsp. majus and H. tetrapterum against C. albicans. These results
      suggest that hypericin and hyperforin are the main components responsible for
      antimicrobial activity, but not the only ones, as other extracts, showing a low
      level of these compounds, possess evident activity. Isolation of pure compounds
      from the most active extracts is in progress.

PMID- 17516333
TI  - The cleft and craniofacial team: the whole is greater than the sum of its parts.
AB  - Cleft and craniofacial healthcare is complex, warranting a specialized,
      multidisciplinary approach. The modern cleft team is best suited to deliver
      appropriate care to both affected individuals and their families.

PMID- 17516334
TI  - Unilateral cleft lip repair by rotation/advancement: potential errors and how to
      avoid them.
AB  - The surgical repair of unilateral cleft lip has been refined over the centuries.
      During the past few decades, two techniques have emerged as ideal: (1) the
      rotation/advancement technique and (2) the triangular flap repair, the former
      more commonly utilized. Underrotation and insufficient advancement represent two
      potential errors when using this technique. In this review, these errors in flap
      development will be examined and strategies discussed for their avoidance.
      Insufficiencies in both rotation and advancement produce functionally and
      aesthetically suboptimal results. Although the principles of rotation and
      advancement are well described, differences in opinions exist as to the precise
      details of flap development. The extent of rotation and the paring point (Millard
      point #8) of the advancement flap will specifically be addressed. It stands to
      reason that the severity of the cleft deformity will determine the required
      surgical intervention. By appropriately applying the techniques herein,
      satisfactory results can be achieved in even severe clefts.

PMID- 17516335
TI  - Two-stage unilateral cleft lip repair.
AB  - Reconstruction of the unilateral cleft lip deformity remains a challenge. The
      Millard repair is the most commonly employed technique of lip closure. Wide
      clefts with malaligned alveolar arches and very short cleft-side philtral ridges
      are particularly difficult to reconstruct well. These cases frequently require
      some degree of cleft-side alotomy with attendant scarring and potential growth
      disturbance. Additionally, the lip scar tends to cross the philtrum at an
      aesthetically unsatisfactory low level. Nasoalveolar molding is one method to
      address these problems, but is not always available or practical. Alternatively,
      a two-stage lip repair serves as a reasonable means of managing these problems as
      well. The first stage, performed at approximately 4 to 6 weeks of age, is a full
      thickness straight-line repair with tip rhinoplasty. The second stage is a
      modified Millard repair done at approximately 6 months of age. An alotomy is
      never needed. The lip scar does not cross the philtrum until the nasolabial
      crease. The alveolar segments are passively brought closer together by the early
      lip repair facilitating anterior palate closure. This technique has been used for
      more than 10 years with satisfying aesthetic and functional results.

PMID- 17516336
TI  - Repair of the bilateral cleft lip deformity.
AB  - The bilateral cleft lip is a complex deformity involving discontinuity of the
      soft tissue layers of the lip and, frequently, the underlying bony structure.
      Satisfactory repair requires a thorough understanding of the anatomic deformity.
      The authors' philosophy and timing of the bilateral cleft lip repair are
      discussed. Details of the surgical technique are outlined.

PMID- 17516337
TI  - Treatment of upper airway obstruction in infants with micrognathia using
      mandibular distraction osteogenesis.
AB  - Mandibular distraction osteogenesis has become an accepted alternative treatment
      for infants and children with upper airway obstruction associated with
      micrognathia. Several reports exist that purport the efficacy of mandibular
      distraction in these patients, such as preventing tracheostomy or facilitating
      tracheostomy removal. However, the majority of these studies are retrospective
      reviews with small cohorts and relatively short-term follow-up. Consequently, the
      ideal indications, pre- and postoperative evaluation, timing, and treatment are
      subject to controversy and not currently well established. Significantly less
      attention has been given to short- and long-term complications of mandibular
      distraction, such as effects on the developing tooth buds, impact on future
      mandibular development, and temporomandibular joint abnormalities. This article
      reviews the basic principles of distraction osteogenesis, summarizes the outcomes
      of recent literature involving pediatric mandibular distraction including this
      author's experience, and discusses the known and potential adverse sequelae of
      mandibular distraction. Before a clearly defined role of mandibular distraction
      in the treatment of infants with micrognathia-associated upper airway obstruction
      can be established, additional prospective studies are necessary to delineate its
      benefits and limitations.

PMID- 17516338
TI  - Presurgical cleft lip management: nasal alveolar molding.
AB  - Continued advancement in the comprehensive care of children with cleft lip and
      palate has resulted in numerous innovative treatment protocols. The cooperation
      of numerous specialties has continued to expand the options for difficult cases.
      A high standard for aesthetic and functional results has been established.
      Presurgical treatment of a cleft alveolus and its associated soft tissues with
      presurgical orthopedics is just one of these techniques. Differing opinions of
      the effectiveness, growth disturbances, and additional costs of presurgical
      molding are often debated, but the concepts should be understood by any cleft
      surgeon or orthodontist involved in cleft care.

PMID- 17516339
TI  - Secondary rhinoplasty in unilateral cleft nasal deformity.
AB  - Secondary rhinoplasty in the unilateral cleft nose represents one of the most
      difficult problems in rhinoplasty surgery. The sliding cheilorhinoplasty
      operation is a procedure that aids the correction of the deformed cleft nose.
      This technique is presented in detail, with operative examples.

PMID- 17516340
TI  - Management of velopharyngeal insufficiency: development of a protocol and
      modifications of sphincter pharyngoplasty.
AB  - Velopharyngeal closure is required for normal speech production. Incomplete
      velopharyngeal closure manifests as resonance disorders and nasal air escape.
      Management of velopharyngeal insufficiency requires a general knowledge of speech
      production as well as a more detailed understanding of the velopharyngeal
      mechanism. Comprehensive evaluation by a velopharyngeal insufficiency team
      includes medical assessment focusing on airway obstructive symptoms, perceptual
      speech analysis, and instrumental assessment, which is utilized to characterize
      the velopharyngeal gap. Options for intervention include speech therapy,
      intraoral prosthetic devices, and surgery. Surgical interventions can be
      categorized as palatal, palatopharyngeal, or pharyngeal procedures. The
      therapeutic challenge lies in achieving velopharyngeal closure during speech
      production while maintaining patency of the upper airway. We present our protocol
      for evaluation of velopharyngeal function with a focus on indications for
      palatoplasty and pharyngoplasty. We also discuss surgical modifications of
      sphincter pharyngoplasty.

PMID- 17516341
TI  - Direct gingivoperiosteoplasty with palatoplasty.
AB  - Gingivoperiosteoplasty creates a mucoperiosteal bridge across the alveolar cleft
      associated with cleft lip and palate. The subperiosteal tunnel allows for bone
      generation in the absence of bone grafting in young patients. The original
      procedure required wide maxillary subperiosteal dissection and flap rotation but
      has since evolved along with techniques to narrow the alveolar cleft toward
      limited dissection and direct closure. Multiple studies reveal superior facial
      growth parameters, particularly vertical maxillary growth, when compared with
      primary bone grafting typically performed within the first year of life and a
      reduced need for later secondary bone grafting. Most centers that perform
      gingivoperiosteoplasty do so in conjunction with primary lip closure after
      initial narrowing of the cleft with presurgical orthopedics. We present our
      method of direct gingivoperiosteoplasty performed simultaneously with
      palatoplasty after alveolar cleft narrowing without presurgical orthopedics via a
      two-stage lip repair. Preliminary data suggest bone growth capable of supporting
      tooth eruption without significant growth disturbances in a majority of patients
      treated with this protocol.

PMID- 17516342
TI  - Transesophageal endoscopic ultrasound-guided access to the heart.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasound and fine-needle aspiration of
      paramural lesions are established diagnostic techniques in gastroenterology and
      are now also used for therapeutic purposes. The proximity of the heart to the
      esophagus and the utility of the diagnostic technique of transesophageal
      echography prompted us to explore the possibilities of approaching the heart
      through the esophagus. METHODS: In acute experiments (n = 2) and survival
      experiments (n = 6) on anesthetized pigs, the anatomical landmarks were first
      identified and studied, before introduction of the needle through the posterior
      cardiac wall into the left atrium, and then beyond, as far as the aortic valve.
      The smallest structure targeted was the coronary artery. The animals in the
      survival group were monitored clinically over a 2-week period and also underwent
      endoscopic and cardiologic re-examinations prior to autopsy. Three patients were
      also investigated using the technique. RESULTS: No visible damage was observed in
      the heart in the two animals which were sacrificed immediately or in the six
      surviving pigs (except for one small hematoma). The needle could be introduced
      repeatedly into the left atrium, followed by the injection of saline. Reaching
      the aortic valve was more difficult because of the moving target, but ablation
      therapy was technically possible. The coronary artery was successfully punctured
      in three of the animals (all three weighed 40 kg or more); in smaller animals,
      the needle overshot the lumen of these minute arteries. Of the three patients
      investigated, pericardial fluid was successfully aspirated in two patients and a
      left atrial mass was punctured in the third patient (excluding neoplasia, the
      final diagnosis being thrombus). CONCLUSION: These animal studies and clinical
      cases suggest that transesophageal intracardiac procedures could become feasible
      and that further exploration by gastroenterologists and cardiologists may be
      justified.

PMID- 17516343
TI  - Peroral transgastric endoscopic primary repair of a ventral hernia in a porcine
      model.
AB  - BACKGROUND AND STUDY AIMS: Multiple studies have demonstrated the feasibility of
      peroral transgastric endoscopic procedures in animal models. The aim of the study
      was to evaluate the feasibility of a peroral transgastric endoscopic approach to
      repair abdominal wall hernias. PATIENTS AND METHODS: We performed acute
      experiments under general anesthesia with endotracheal intubation using 50-kg
      pigs. Following peroral intubation an incision of the gastric wall was made and
      the endoscope was advanced into the peritoneal cavity. An internal anterior
      abdominal wall incision was performed with a needle knife to create an animal
      model of a ventral hernia. After hernia creation an endoscopic suturing device
      was used for primary repair of the hernia. After completion of the hernia repair
      the endoscope was withdrawn into the stomach and the gastric wall incision was
      closed with endoscopic clips. Then the animals were killed for necropsy. RESULTS:
      Two acute experiments were performed. Incision of the gastric wall was easily
      achieved with a needle knife and a pull-type sphincterotome. A large (3 x 2 cm)
      defect of the abdominal wall (ventral hernia model) was closed with five or six
      sutures using the endoscopic suturing device. Postmortem examination revealed
      complete closure of the hernia without any complications. CONCLUSIONS:
      Transgastric endoscopic primary repair of ventral hernias in a porcine model is
      feasible and may be technically simpler than laparoscopic surgery.

PMID- 17516344
TI  - Endoscopic transgastric procedures in anesthetized pigs: technical challenges,
      complications, and survival.
AB  - BACKGROUND AND STUDY AIMS: An incisionless endoscopic peroral transgastric
      approach to the peritoneal cavity has shown promise in animals as a potentially
      less invasive form of surgery. We present our experience with various endoscopic
      peroral transgastric procedures, reporting on the technical aspects and
      challenges that arose. MATERIALS AND METHODS: The following procedures were
      performed in 10 anesthetized pigs using a double-channel endoscope:
      peritoneoscopy (10 pigs), liver biopsy (one pig), cholecystectomy (six pigs),
      fallopian tube excision (one pig), and hysterectomy (one pig). RESULTS: All the
      procedures were accomplished successfully. There were six minor intraoperative
      complications. Complete gastric cleansing and elimination of all bacteria was
      found to be impossible to achieve in the porcine model. Overinflation was a
      common problem. The lack of adequate endoscope support was a major limitation.
      Safe closure of the gastrotomy incision was difficult using the available
      clipping devices. Six pigs made an uncomplicated recovery after a follow-up
      period of 4-6 weeks. Subsequent pathological examination revealed deep gastric
      ulceration in one animal and a gastric wall abscess in another. CONCLUSIONS:
      Peroral transgastric surgery is technically feasible and safe in a porcine model.
      Although all the procedures were performed successfully, the study highlights
      some technical difficulties and illustrates the need for major technical
      innovations and extensive animal studies in order to evaluate the merits of
      incisionless surgery.

PMID- 17516345
TI  - An innovative, safe and sterile sigmoid access (ISSA) for NOTES.
AB  - BACKGROUND AND STUDY AIMS: The use of a transcolonic approach for natural orifice
      transluminal endoscopic surgery (NOTES) offers relevant advantages compared with
      a transgastric procedure. However both techniques are still limited by specific
      shortcomings that need to be resolved before the transluminal approach can be
      translated to human applications. In this article we describe an innovative
      method for a transcolonic procedure, which might represent the next step forward
      in NOTES. PATIENTS AND METHODS: In three acute and five survival porcine models
      we evaluated a specially designed guide tube, which is inserted via a
      transcolonic approach into the abdominal cavity after intraperitoneal
      instillation of a decontamination solution. After endoscopic evaluation of the
      abdomen the closure of the entry site was performed surgically. Main parameters
      obtained in the study were the feasibility and safety of the approach, the
      bacterial contamination due to the transcolonic procedure, and the safe closure
      of the entry site. Animals in the survival model were euthanized 10 days after
      the procedure. RESULTS: The transcolonic approach took place without
      complications. There was no bleeding or laceration of adjacent organs. The
      surgical closure guaranteed a leak-proof closure of the entry site. All pigs in
      the survival model showed an excellent postinterventional course. At necropsy,
      the colonic incision sites were completely closed and appeared well healed. No
      abscesses or any sign of inflammation could be identified. CONCLUSIONS: The
      transcolonic approach using an innovative guide tube is feasible and safe. The
      technique described offers mentionable advantages and therefore reduces the known
      shortcomings of NOTES. However, further studies are needed to approve our results
      of an initial evaluation.

PMID- 17516346
TI  - Transgastric in vivo histology in the peritoneal cavity using miniprobe-based
      confocal fluorescence microscopy in an acute porcine model.
AB  - BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery
      (NOTES) is an emerging technology. Apart from its therapeutic implications, this
      type of access to the peritoneal cavity might also be useful for targeted in vivo
      histological investigation by means of confocal fluorescence microscopy. In this
      study we therefore aimed to assess the feasibility of miniprobe-based confocal
      fluorescence microscopy during transgastric endoscopy in an acute porcine model.
      MATERIALS AND METHODS: Transgastric in vivo histology was performed in five pigs,
      under general anesthesia. After incision of the anterior gastric wall, a double
      channel video gastroscope was advanced into the peritoneal cavity. A flexible
      confocal miniprobe was introduced through the instrument channel of the endoscope
      after intravenous injection of 10 mL of fluorescein 1% in four of the pigs and of
      50 mL of fluorescein isothiocyanate-dextran 150 000 4% in the fifth pig. The tip
      of the miniprobe was then placed on the peritoneal layer, the liver, and the
      spleen for confocal laser microscopy. RESULTS: Probes were easily attached to the
      peritoneal layer, the liver, and the spleen under direct visualization with the
      endoscope. Dynamic microscopic images of these organs were obtained with a frame
      rate of 12 frames per second. The flow of erythrocytes through blood vessels
      could be seen. The microstructural components of organs, such as lobules of the
      liver, were also easily identified. CONCLUSIONS: In vivo histology in the
      peritoneal cavity is feasible during NOTES and this technique combines the
      minimally invasive approach to the intraperitoneal organs afforded by NOTES and
      real-time, in vivo acquisition of dynamic histological images.

PMID- 17516347
TI  - Proof-of-concept study of the Aer-O-Scope omnidirectional colonoscopic viewing
      system in ex vivo and in vivo porcine models.
AB  - BACKGROUND AND STUDY AIMS: The limited angle of view of standard colonoscopes
      means that lesions can be missed. A multidirectional viewing system (OmniVision)
      has been developed recently and has been incorporated into the Aer-O-Scope (GI
      View Ltd., Ramat Gan, Israel), a disposable, self-propelling, and self-navigating
      colonoscope. The objectives of this study were to qualitatively assess the
      sensitivity of this viewing system in an ex vivo porcine polyp induction model,
      and to demonstrate its feasibility and safety in live pigs. MATERIALS AND
      METHODS: For the ex vivo part of the study, six red metal beads of various sizes
      were randomly sewn into the mucosa of an unfolded, 2-meter-long porcine colonic
      segment. Seven passages of the Aer-O-Scope were video-recorded separately and
      blindly reviewed by six experienced gastroenterologists. The sensitivity of the
      Aer-O-Scope to detect beads of various sizes was calculated. For the in vivo
      experiment, in a repeated-measure study, nine female domestic pigs were examined
      with the Aer-O-Scope with the OmniView optics, followed immediately by
      examination with standard optical colonoscopy in order to assess the integrity of
      the colonic mucosa. RESULTS: In the ex vivo study the sensitivity of the Aer-O
      Scope was 97.6% (CI 94.0%-100%) for any bead (i. e. any "polyp"). The rate of
      polyp detection was similar for the six endoscopists, and was consistent for all
      bead sizes. The average false-positive rate was 0.3% polyps per run (SD 0.61%).
      The mean time taken for the video assessment was 8.0 minutes (SD 4.0 minutes). In
      the in vivo experiments with the Aer-O-Scope, both the front-viewing and
      omnidirectional-viewing systems were functional in all cases. The colon in front
      of the optical capsule was well distended and a complete and meticulous
      inspection of the entire colonic mucosa was performed in all the pigs. There were
      no adverse events. CONCLUSIONS: The OmniVision system allows for a highly
      sensitive inspection of the colonic mucosa without the need for tip manipulation.
      Clinical studies are warranted in order to validate these results in humans.

PMID- 17516348
TI  - Endoscopic submucosal dissection: a safe technique for colorectal tumors.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) aims to resect
      large neoplastic lesions en bloc, allowing for more precise histopathological
      analysis. The present retrospective study aimed to analyze the technical and
      clinical outcomes after ESD of colorectal tumors. PATIENTS AND METHODS: ESD was
      performed for the treatment of 71 colorectal neoplasms in 70 patients (38 men, 32
      women; mean age 63.4 years). Lesion size, procedure time, complications, and
      immediate and follow-up outcomes were evaluated. The results for these 71 lesions
      were compared with those for a group of 32 lesions treated by conventional
      piecemeal endoscopic mucosal resection (EMR) performed during the same period.
      RESULTS: For the ESD-treated group of lesions, the average lesion size was 32.7
      mm (range 13-80 mm), and the mean operating time was 61.1 minutes (range 7-164
      minutes). One perforation occurred in the ESD group (1.4%) and this was treated
      conservatively with clipping. The majority of these lesions (n = 50) were
      laterally spreading tumors. Histological examination showed low-grade adenoma in
      12 cases; high-grade intraepithelial neoplasia in 47 cases; and submucosally
      invasive cancer in 11 cases, of which four were sm1, and seven were sm2 or sm3
      (these seven patients underwent surgery). The en bloc resection rate was 98.6%.
      For the 64 tumors that were treated by radical endoscopic resection, no tumor
      recurrence was found after a mean follow-up period of 12.2 months (range 3-34
      months) and a mean of 2.1 follow-up endoscopies (range 1-4). This contrasted with
      the 6.3% recurrence rate in the 32 piecemeal EMR cases (mean tumor size 28.7 mm,
      range 20-60 mm). CONCLUSION: In our hands, ESD is a safe and effective resection
      technique for large colorectal neoplasms. As experience with the technique
      increases, it might gradually replace piecemeal EMR in the majority of cases.

PMID- 17516349
TI  - Submucosal injection, for endoscopic mucosal resection, of photocrosslinkable
      chitosan hydrogel in DMEM/F12 medium.
AB  - BACKGROUND AND STUDY AIMS: We studied the ability of a photocrosslinkable
      chitosan in DMEM/F12 medium to maintain submucosal thickness and to reduce
      bleeding after mucosal resection. We also investigated the behavior of chitosan
      hydrogels with regard to wound healing. METHODS: The gastric submucosal layer of
      heparinized rats was injected with the photocrosslinkable chitosan in medium
      (which was then irradiated with ultraviolet light to form a hydrogel), or with
      sodium hyaluronate, or hypertonic saline, and three investigations were done,
      using three different sets of rats. The first and second were measurement of the
      thickness of the layer, and of the amount of bleeding induced by mucosal
      resection, respectively. Thirdly, the effects of the chitosan hydrogel on wound
      healing were examined histologically. RESULTS: Gastric submucosal layers of
      chitosan hydrogel-treated animals remained significantly thicker than those of
      other groups for at least 6 h after injection. The total amount of bleeding 20
      min after mechanical mucosal resection was 170.0 +/- 20.0 mg, 678.3 +/- 226.3 mg,
      and 1020.0 +/- 104.1 mg in the chitosan hydrogel, sodium hyaluronate, and
      hypertonic saline groups, respectively. Histological study revealed that the
      focus of bleeding was surrounded by chitosan hydrogel and that almost all the
      hydrogel was biodegraded within 4 weeks. Furthermore, a discernible, but not
      statistically significant effect of the chitosan hydrogel on wound healing was
      observed. CONCLUSIONS: The chitosan hydrogel produced mucosal elevation after
      submucosal injection with ultraviolet irradiation, and it significantly reduced
      bleeding after mucosal resection. Our newly developed chitosan hydrogel in medium
      might be a promising submucosal agent for endoscopic mucosal resection.

PMID- 17516350
TI  - First data on the palliative treatment of patients with malignant gastric outlet
      obstruction using the WallFlex enteral stent: a retrospective multicenter study.
AB  - BACKGROUND AND STUDY AIMS: Gastric outlet obstruction can occur as a late
      complication of a variety of cancers. Palliation of the obstructive symptoms is
      the primary aim of treatment in these patients. Self-expandable metal stents have
      emerged as a promising treatment option. The purpose of this study was to
      investigate the short-term (30-day) clinical success and complication rates of a
      new enteral stent made of nitinol (Boston Scientific WallFlex stent). PATIENTS
      AND METHODS: Between December 2004 and 1 May 2005, 62 patients (35 men, 27 women;
      mean age 69.9 years) presenting with documented malignancy and symptoms of
      gastric outlet obstruction underwent endoscopic stenting with the new WallFlex
      enteral stent at one of the 15 European centers who were the first to have access
      to this new stent. Data were collected from charts, endoscopy procedure reports,
      and follow-up clinical visits. The gastric outlet obstruction scoring system
      (GOOSS) was used to grade the patients' ability to eat. RESULTS: All 62 patients
      suffered from nausea, vomiting, or inability to eat. A total of 66 enteral stents
      were placed. The median length of the stenosis was 4 cm. The clinical success
      rate was 85% on an intention-to-treat basis. An improvement in the GOOSS score of
      1 point was considered to be significant (P < 0.001). Oral intake was possible,
      on average, 1 day after stent placement. The median hospital stay was 6 days.
      Thirty days' follow-up data were available for 60 patients, 10 of whom developed
      complications during this period (17%). CONCLUSIONS: In this first European
      series in which duodenal stenting was performed with the WallFlex enteral stent,
      the new stent appears to be effective and relatively safe for the palliative
      treatment of patients with malignant gastric outlet obstruction.

PMID- 17516351
TI  - Combined endoscopic stent insertion in malignant biliary and duodenal
      obstruction.
AB  - BACKGROUND AND STUDY AIMS: Self-expandable metal stents (SEMS) are an effective
      palliative treatment for malignant biliary and duodenal strictures. Combined
      biliary and duodenal stenting remains a technical challenge, however. The aim of
      this study was to evaluate the technical feasibility of an endoscopic approach to
      double stenting of malignant biliary and duodenal strictures. PATIENTS AND
      METHODS: Consecutive patients referred for palliative gastroduodenal and biliary
      stenting were followed up prospectively. Patients' demographic characteristics,
      the site and nature of the strictures, success rates, complications, and survival
      time were recorded. RESULTS: A total of 64 patients underwent double stenting. In
      46 patients, biliary obstruction occurred before the onset of duodenal
      obstruction (by a median of 107 days) (group 1); in 14 patients, biliary
      obstruction occurred concurrently with duodenal obstruction (group 2); and in
      four patients the duodenal obstruction preceded the biliary obstruction (by a
      median of 121 days) (group 3). The duodenal strictures were proximal to the
      papilla in 31 patients, adjacent to the papilla in 25 patients and distal to the
      papilla in eight patients. The majority of biliary strictures were in the middle
      or distal third of the bile duct (in 52/64 patients). Duodenal SEMS were
      successfully deployed in all patients. Combined endoscopic stenting was
      successful in 100% of patients in group 1, 86% of patients in group 2, and in
      100% of patients in group 3. Taking the three groups together, early
      complications occurred in 6% of patients and late complications occurred in 16%
      of patients. The overall median survival after combined stenting was 81 days
      (range 2-447 days). CONCLUSIONS: Combined endoscopic biliary and duodenal SEMS
      insertion is safe and effective for palliation in malignant biliary and duodenal
      obstruction. Biliary stenting through the mesh of the duodenal SEMS is
      technically feasible and has a high success rate.

PMID- 17516352
TI  - A dual-design expandable colorectal stent for malignant colorectal obstruction:
      results of a multicenter study.
AB  - BACKGROUND AND STUDY AIMS: It is known that metal stent placement is safe, easy,
      and effective for the treatment of malignant colorectal obstruction, but these
      stents are associated with delayed complications of tumor ingrowth and stent
      migration. The aim of this study was to prospectively investigate the technical
      feasibility, clinical effectiveness, and safety of a dual-design colorectal stent
      (consisting of an outer stent and an inner bare nitinol stent) in patients with
      malignant colorectal obstruction. PATIENTS AND METHODS: Placement of the dual
      stent using a 4.5-mm stent delivery system was attempted in 151 patients with
      malignant colorectal obstruction, either before surgery (n = 50) or for
      palliation (n = 101). Multivariate logistic regression analysis was used to
      identify risk factors associated with complications. RESULTS: Stent placement was
      technically successful in 145/151 patients (96%). Of the patients who had a
      technically successful placement, bowel obstruction resolved within 2 days after
      stent placement in 48/50 (96%) of the patients in the bridge-to-surgery group and
      in 87/95 (92%) of the patients in the palliative group. Perforation occurred in
      16 patients, incomplete stent expansion in eight patients, stent migration in
      four patients, tumor overgrowth in five patients, severe rectal pain in five
      patients, and bleeding in eight patients. Complete obstruction was the only
      significant risk factor for perforation (odds ratio 6.88, 95% CI 2.04-23.17, P =
      0.002). In the palliative group, the median survival was 152.0 days and the mean
      survival was 263.8 days. CONCLUSIONS: The dual stent with a 4.5-mm stent delivery
      system is easy to insert, safe, and reasonably effective for the palliative
      treatment of malignant colorectal obstruction. However, a great deal of care is
      needed in its deployment because of the high rate of perforation.

PMID- 17516353
TI  - Capsule endoscopy in refractory celiac disease.
AB  - BACKGROUND AND STUDY AIMS: Patients with refractory celiac disease (RCD) are at
      risk of intestinal T-cell lymphoma, which is difficult to diagnose because it
      often develops in the small bowel. We therefore studied whether wireless capsule
      endoscopy was able to detect ulcerative jejunitis or intestinal T-cell lymphomas
      that were missed by standard endoscopic and imaging procedures in patients with
      RCD. PATIENTS AND METHODS: Detection of ulcerative jejunitis and overt T-cell
      lymphoma by capsule endoscopy or by upper and lower endoscopy, abdominal computed
      tomography (CT) or abdominal magnetic resonance tomography (MRT) was compared in
      14 consecutive patients with RCD: in seven patients who showed loss of T-cell
      antigens on intraepithelial lymphocytes and/or clonality of the T-cell receptor
      gene (i. e. type II RCD) and in seven patients who did not have these features
      (i. e. type I RCD). RESULTS: Complete evaluation of the small bowel by capsule
      endoscopy was achieved in 9/14 patients. Signs of ulcerative jejunitis or
      intestinal T-cell lymphoma, affecting further clinical management, were found in
      two patients with type II RCD: in one patient these signs were found only by
      capsule endoscopy (ulcerations and stenosis) and in another patient the
      abnormalities were identified by CT/MRT (mesenteric lymph nodes harboring
      lymphoma). No clinically relevant abnormalities were found in patients with type
      I RCD by lower endoscopy or by small-bowel imaging (capsule endoscopy, CT, or
      MRT). CONCLUSIONS: In patients with type II RCD, capsule endoscopy can detect
      additional cases with ulcerative jejunitis and could be included in the
      diagnostic armamentarium, subject to confirmation by larger series. In patients
      with type I RCD, our study confirmed the low diagnostic yield of imaging
      procedures, including wireless capsule endoscopy.

PMID- 17516354
TI  - Cat scratch colon.
AB  - BACKGROUND: Bright red linear marks in the right colon are occasionally seen but
      have never been described in the medical literature. We have termed this finding
      "cat scratch" colon. METHODS: This was a prospective examination of 8277
      colonoscopies at a single endoscopy center in a private practice setting. All
      cases of cat scratch colon were biopsied, and the results read by two
      pathologists. RESULTS: A total of 21 cases of cat scratch colon were identified,
      all in the ascending colon and cecum, with a prevalence of 0.25%. The majority of
      cases were in women. Although the colon was histologically normal in most cases,
      there was a significantly higher proportion of collagenous colitis in patients
      with cat scratch colon compared with the total cohort (14% vs. 0.15%).
      CONCLUSIONS: The prevalence of bright red linear markings (cat scratch colon) in
      the cecum and ascending colon is 0.25%. These markings appear to be superficial
      breaks in the mucosa possibly secondary to barotrauma. Patients tend to be older
      women with higher proportion of collagenous colitis.

PMID- 17516355
TI  - The ShapeLock system adapted to intragastric and transgastric surgery.

PMID- 17516356
TI  - Endoscopic treatment combined with laparoscopic sentinel node mapping for
      superficial gastrointestinal cancers.

PMID- 17516357
TI  - Magnification with chromoendoscopy is the most reliable method to determine
      whether colorectal lesions are neoplastic or not.

PMID- 17516360
TI  - Sclerotherapy and esophageal variceal bleeding: time to forget it, or not?

PMID- 17516361
TI  - Iron deficiency anemia: don't forget gastric atrophy!

PMID- 17516363
TI  - Mechanism of acute pancreatitis after peroral double-balloon enteroscopy.

PMID- 17516366
TI  - [Legal aspects in ophthalmological expert assessment: part I].

PMID- 17516367
TI  - [The 'cup-to-disc ratio': a comparison of TopSS, HRT II and subjective findings].
AB  - PURPOSE: One of the major shortcomings of longitudinal studies is the fact that
      instruments and technologies which were used at the beginning of the sampling
      might be replaced by others during the course of the study. The aim of the
      present work is to evaluate the relationship of optic disk parameters assessed
      with different methods and to test statistical possibilities of transforming
      these parameters into each other. PATIENTS AND METHODS: The 'cup-to-disc ratio',
      the 'total disc area' and the 'neuroretinal rim area' of the human optic nerve of
      131 eyes of 66 patients participating in the Salzburg-Moorfields Collaborative
      Glaucoma Study were assessed with two different laser scanning methods (TopSS and
      HRT II. The 'cup-to-disc ratio' was also determined subjectively by
      ophthalmologists of the glaucoma department. To compare the three data sets, the
      method of Bland-Altman, paired t-tests, as well as regression analyses were
      applied. RESULTS: The 'cup-to-disc ratios' were: HRT II(R): 0.26 (95 % CI: 0.23 -
      0.28), subjective assessment of 'cup-to-disc ratio': 0.33 (0.30 - 0.36) and
      TopSS: 0.43 (0.40 - 0.46). All three results are statistically significantly
      different (pairwise comparisons, p < 0.00001 each). Bland-Altman analysis shows
      that the differences of both objective methods exceed a magnitude that can be
      accepted for clinical purposes. The regression analyses reveal that the slope
      parameters are significantly different from 1.0. No regression models could be
      found with sufficiently small differences. DISCUSSION: There are significant
      differences in the 'cup-to-disc Ratios' observed between the three methods.
      Therefore the application of a 'correction factor' cannot be advocated. Although
      such factors allow the means of the samples to agree, the differences of
      individual measurements still remain too large, to be useful for practical
      purposes.

PMID- 17516368
TI  - [Retrobulbar haemodynamics in normal and high tension glaucoma patients: the
      diagnostic importance of tinnitus, migraine and Raynaud-like symptoms].
AB  - BACKGROUND: In the pathophysiology of open-angle glaucoma altered perfusion of
      the optic nerve head is of importance. Up to now these disturbances were presumed
      to be the chief cause of glaucomatous damage in patients with normal tension
      glaucoma showing other vascular disturbances like migraine or tinnitus. PATIENTS
      AND METHODS: Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were
      measured and the resistive index (RI) was calculated by colour Doppler imaging
      (CDI) in the ophthalmic artery (OA), central retinal artery (CRA) and in the
      short and long posterior ciliary arteries (SPCA, LPCA) in 18 patients with normal
      tension glaucoma (NTG), in 18 patients with high tension glaucoma (HTG) and in 18
      normal control subjects. RESULTS: In an upright sitting position both glaucoma
      groups showed statistically significant decreases in PSV and EDV in CRA and SPCA
      compared to the control subjects. HTG when compared to NTG and normal subjects
      showed statistically significant decreases of EDV and statistically significant
      increases of RI in LPCA. In addition, compared to normal subjects, HTG patients
      showed statistically significant increases of RI in both OA and SPCA. DISCUSSION:
      Both glaucoma groups showed decreased blood flow velocities in the small
      retrobulbar vessels in an upright sitting position. Normal tension glaucoma
      patients with symptoms of vasospasms compared to patients with high tension
      glaucoma showed only small differences in ocular haemodynamics.

PMID- 17516369
TI  - [Spectometric measurement of oxygen saturation in retinal vessels].

PMID- 17516370
TI  - [Change of retinal oxygen saturation in healthy subjects and in early stages of
      diabetic retinopathy during breathing of 100% oxygen].
AB  - BACKGROUND: Disturbances in the microcirculation are a source of retinal diabetic
      alterations. Comprehensive studies of blood flow parameters have been performed,
      but it is not known how ageing, duration of diabetes, blood sugar, glycolysed
      haemoglobin and elevated systemic blood pressure act in the early stages of
      diabetic retinopathy. MATERIAL AND METHODS: The arterial and venous oxygen
      saturation (aOS, vOS) were measured with a Jena Ophthalmo Spectrometer in 28
      healthy subjects (NP) (30.3 +/- 13.1 years), 31 Type I diabetics (T I) (42.2 +/-
      12.9 years), and in 25 Type II diabetics (T II) (58.9 +/- 6.9 years), suffering
      form mild or moderate non-proliferative diabetic retinopathy, before, during
      breathing of 100 % oxygen for 6 minutes, and after respiration of air during 10
      minutes. RESULTS: Before oxygen breathing, the venous oxygen saturation in
      diabetics increased with age. During breathing of 100 % oxygen, the vOS increased
      considerably by 20 % in all groups. The arterio-venous difference of oxygen
      saturation was decreased with age in diabetics, but there was no dependence on
      age in normals. In Type II diabetics, the vOS before oxygen breathing was
      increased with HbA1c. There was also a positive correlation between vOS and blood
      pressure before oxygen breathing. CONCLUSION: Healthy subjects and diabetics in
      the early stages of diabetic retinopathy exhibit comparable changes of oxygen
      saturation during breathing of 100 % oxygen. Measurements of venous OS are most
      evident. First differences were detectable between diabetics and normals in the
      normalisation after oxygen respiration.

PMID- 17516371
TI  - [Static vessel analysis in nonmydriatic and mydriatic images].
AB  - BACKGROUND: Static vessel analysis is a method to determine the diameter of
      retinal vessels in images of the ocular fundus. The suitability of non-mydriatic
      and mydriatic images for that method and the influence of mydriasis on the
      results were examined. MATERIALS AND METHODS: In the prospective study, 30 eyes
      of 15 patients (10 women, mean age 51.6 +/- 13.2 years) were examined. At first,
      3 images were taken of each eye with the retinal camera Topcon NW 200
      (magnification 1). After pupil dilation with tropicamid eye drops, 3 more images
      were taken using the Topcon and 3 others using the system Visualis (IMEDOS,
      Jena/Germany, FF450plus, 535-561 nm, 30 degrees image, 1840 x 1360 pixel). The
      vessel diameters were measured with the software Vesselmap2 (IMEDOS). The
      investigator assigned vessels to arteries or veins and their diameters were
      calculated automatically by the software. There is the possibility to define the
      vessel edge manually in cases of a poor image quality. The calculation of the
      central retinal arterial and venous equivalent (CRAE, CRVE) as well as the
      arterio-venous ratio (AVR) were made according to the formula of Parr-Hubbard.
      Furthermore, the nasal retinal vessels > 60 microm were examined to estimate the
      influence of tropicamid on the vessel diameter. RESULTS: Because of insufficient
      illumination and poor contrast in 21 % of the non-mydriatic images not all
      vessels could be detected automatically. Additionally, fewer vessels could be
      detected in 7 % of the non-mydriatic images compared to the mydriatic images. The
      average coefficient of variation of CRAE and AVR of each triplet of images was
      higher in non-mydriatic images (2.6 % and 3.2 %, respectively) than in mydriatic
      images of the Topcon (1.8 %; 2.3 %) and the FF 450 (1.7 %; 1.8 % ANOVA p < 0.05).
      No significant differences were found between the various examination methods for
      both the coefficient of variation of CRVE (1.9 %; 1.8 %; 1.7 %) and the average
      values of CRAE, CRVE and AVR. With regard to their diameters, the nasal retinal
      arteries and veins > 60 microm, were depicted sufficiently in all images, and
      only differed insignificantly between the three methods. CONCLUSION: The quality
      of non-mydriatic images is often lower than that of mydriatic images. This fact
      can account for the high variance of measured parameters in the non-mydriatic
      images. The depiction of all relevant vessel segments is a precondition for the
      image-based analysis. An influence of the mydriasis caused by tropicamid on the
      retinal vessel diameters > 60 microm was not found.

PMID- 17516372
TI  - [Are screening examinations necessary in ruling out ocular malformations after
      reproduction treatment?].
AB  - BACKGROUND: In-vitro fertilization (IVF) is an established procedure frequently
      used for the treatment of infertility. However, the risk of twin or triplet
      pregnancies with premature birth and presumably also malformations is increased
      in IVF/ICSI pregnancies. Specific ophthalmological examinations so far were
      published by Anteby et al., who reported about an increased incidence of ocular
      malformations. METHODS: In a retrospective study we analysed the medical
      histories of 30 newborn and premature children born after IVF/ICSI (almost
      exclusive twin pregnancies) which were cared for in the department of neonatology
      and intensive care from 2002 to 2004 and had an ophthalmological examination. A
      follow-up control was carried out in 2005 to check the developmental status of
      the visual organ. RESULTS: Systemic malformations such as cardiovascular
      malformations of different severity and haemangioma were diagnosed in 6 children.
      Malformations of the visual organ were only found in one male infant (congenital
      glaucoma because of missing Schlemm canal). His twin sister had showed a
      cardiovascular malformation. The father of these children suffered from OAT
      (oligoasthenoteratozoospermia) syndrome with an inversion at chromosome 3.
      Retinopathia pramaturorum requiring treatment was not observed in any child.
      CONCLUSIONS: Pregnancies following reproduction treatment are associated with a
      higher risk for malformations. Systematic ophthalmological examinations maybe
      considered in infants of IVF/ICSI pregnancies.

PMID- 17516373
TI  - [Inflammatory juvenile conjunctival nevus (IJCN)].
AB  - BACKGROUND: Pathologists may occasionally have difficulties in reliably assessing
      the dignity of tumour cells in histological sections, especially in nevi with
      junctional activity. PATIENT HISTORY: This case history of a boy suffering from
      an inflammatory juvenile conjunctival nevus (IJCN) is reported with a follow-up
      period of 25 years. Seven years after first surgical treatment of a
      histologically proven nevus, a recurrent pigmented lesion within the former
      operation area aroused the suspicion of it being a malignant melanoma. Logically,
      a second excision was performed followed by cryotherapy with liquid nitrogen
      (spray freezing). The histological diagnosis performed by a pathologist resulted
      in a malignant melanoma. A second recurrent pigmented conjunctival tumour
      developed fourteen years later. This lesion again aroused another strong clinical
      suspicion of malignant transformation into a melanoma. However, the histological
      examination of the biopsy at this time only showed benign nevus cells and areas
      of conjunctival melanosis without atypia. DISCUSSION: Especially in young
      patients, IJCN must be regarded as an independent type of nevus, which might lead
      even experts in ophthalmic pathology to over-diagnose this lesion as a malignant
      melanoma. This could mean that the wrong therapeutic steps were taken with
      surgical procedures that cause unnecessary mutilation. A reappraisal of the
      former histological specimens of the first recurrent tumour by other pathologists
      came to the conclusion that the initial diagnosis of melanoma could not be
      maintained. Nevertheless, we also strongly recommend follow-up examinations at
      regular intervals in cases of IJCN since we are aware of the fact that
      melanocytic tumours of the conjunctiva behave unpredictably.

PMID- 17516374
TI  - [Diagnostics of Sjogren's syndrome by means of anti-alpha-fodrin antibody].
AB  - BACKGROUND: Sjogren's syndrome (SS) is a common connective tissue disease
      concerning 0.5 % of the white population. Typical symptoms are dry eyes and a dry
      mouth. The diagnostics of SS often are difficult, especially during early stages
      of the disease as long as the leading symptoms have not yet fully developed.
      Previously employed serum antibodies have neither been sensitive nor specific
      enough to be able to differentiate SS from different rheumatic diseases. We
      report on a patient with relapsing corneal erosions. In his case we have been
      able to support the diagnosis of SS by detecting the anti-alpha-fodrin-antibody
      as well as antinuclear antibodies. CASE REPORT: The patient appeared with
      incomplete closure of the eyelids and corneal ulcers on both eyes. Smears of the
      conjunctivae from both eyes were sterile. Schirmer's test indicated a decrease in
      tear production with 5 mm in the right eye and a normal tear production with 19
      mm in the left eye. Three months before, the results of this test had been even
      more pronounced with 1 mm and 3 - 4 mm, respectively. Additionally the patient
      described relapsing erosions and a dry mouth. We then examined his blood to help
      diagnose SS. Results were negative for rheumatoid factor, anti-Ro/SSA antibody
      and anti-La/SSB antibody, but positive for anti-nuclear-antibodies. In order to
      spare the patient an invasive biopsy we examined the anti-alpha-fodrin-antibody
      which was positive. CONCLUSION: Even with negative anti-Ro/SSA and anti-La/SSB
      antibodies the positive anti-alpha-fodrin-antibody supported the diagnosis of SS.
      Therefore, we consider it a useful addition to the diagnostics previously
      employed in the diagnosis of SS (Schirmer's-test, anti-Ro/SSA-AK, anti-La/SSB-AK,
      rheumatoid factor, eventually biopsy).

PMID- 17516375
TI  - [Foreign bodies of the iris as a rare differential diagnosis of malignant
      melanoma of the iris].
AB  - BACKGROUND: Lesions of the iris require a thorough examination to differentiate
      them from malignant melanoma because of the severe therapeutic consequences of
      the latter entity. METHODS: We observed two cases with a unilateral lesion on the
      iris, both suspicious of malignant melanoma of the iris. Ophthalmological,
      echographic and ultrasound biomicroscopic examinations were done. RESULTS: The
      cases of a 66-year-old man with a metallic foreign body and a 37-year-old man
      with a foreign body, both located on the iris, are presented. CONCLUSION: In both
      patients an unclear lesion of the iris, suspicious of a malignant melanoma of the
      iris, turned out to be a foreign body after ophthalmoscopic examination. Both
      echography and ultrasound biomicroscopy were carried out and proved to be useful
      to confirm the diagnosis. No ocular inflammations, siderosis or secondary
      glaucoma occurred in the described cases. Observation of dormant foreign bodies
      is sufficient.

PMID- 17516376
TI  - [Effects of the long-term tamponade with Densiron on the lens].
AB  - BACKGROUND: This study aims to analyse the long-term effect of Densiron on the
      crystalline lens. MATERIALS AND METHODS: Eleven patients (53-77 years old)
      underwent macular surgery with pars plana vitrectomy and intraocular tamponade
      with Densiron. After 2-4 months the Densiron was removed. The lens was extracted
      by phacoemulsification and an intraocular lens was implanted. Visual acuity, slit
      lamp examination and fundus ophthalmoscopy were performed pre- and
      postoperatively. During surgery the anterior chamber, the lens und the posterior
      capsule of the lens were photographed and analysed. RESULTS: All patients (mean
      age: 68 +/- 7 years) developed a nuclear cataract combined with a posterior
      capsule opacification. Four patients demonstrated vacuoles within the lens cortex
      and in five patients a pseudohypopyon consisting of emulsified Densiron was
      found. Mean visual acuity was 0.1 before removal of Densiron and 0.1
      postoperatively. CONCLUSIONS: Long-term tamponade with Densiron was complicated
      by early cataract formation in patients aged 68 years on average. The additional
      posterior capsule opacification showed a distinct pattern and localisation when
      compared to the use of 5000 mPas-silicone oil as tamponade.

PMID- 17516377
TI  - [Steroid glaucoma after laser in situ keratomileusis].
AB  - BACKGROUND: A steroid-induced glaucoma may develop after bilateral laser in situ
      keratomileusis (LASIK) with normal intraocular pressure in applanation tonometry.
      METHODS: We present the case of a 32-year-old patient who underwent bilateral
      LASIK for myopia. Postoperatively, a steroid-induced glaucoma developed. After
      the steroid therapy was stopped applanation tonometry showed normal values. A
      slight corneal opacity was interpreted as a keratokonjunctivitis sicca because of
      occupational noxa. One year after LASIK, the patient presented with high
      intraocular pressure (IOP), maximally excavated optic nerve head and extensive
      visual fields defect in both eyes. CONCLUSION: Elevated IOP after LASIK can lead
      to fluid accumulation in the interface. In this case applanation tonometry can
      underestimate the intraocular pressure. Even when steroid therapy is stopped, the
      elevated pressure can persist. This complication after LASIK is very rare and can
      cause severe damage if not diagnosed.

PMID- 17516378
TI  - [Tuberous sclerosis: an interdisciplinary diagnosis].
AB  - BACKGROUND: Tuberous sclerosis is a relatively rare disease, but it often takes a
      progressive and severe course. We wish to demonstrate the typical changes in a
      patient with tuberous sclerosis and their relevance for the ophthalmologist.
      FINDINGS: Ophthalmologic evaluation including funduscopy, 30 degree perimetry and
      fundus photography and clinical course of a 40-year-old man are described. We
      observed an elevated, multinodular, opaque hamartoma resembling mulberries,
      approximately (1/3)-(1/2) PD large, at the temporal superior arc with
      corresponding visual field defects. CONCLUSIONS: An ophthalmologist should always
      think of a tuberous sclerosis as a differential diagnosis when confronted with a
      retinal hamartoma. Other characteristic ophthalmological findings include facial
      and eyelid angiofibromas, coloboma of the iris, lens and choroid, strabismus,
      poliosis of the eyelashes, papilloedema and sector iris depigmentation. Clinical
      diagnosis of tuberous sclerosis is in most cases relatively easy; however, an
      interdisciplinary cooperation is needed.

PMID- 17516379
TI  - [Mors porta vitae. In memoriam Prof. Dr. Med. Wolfgang Gottinger (1940-2006)].

PMID- 17516380
TI  - [Editorial comment on Burkhardt Soares S. et al.: retroperitoneal fibrosis].

PMID- 17516381
TI  - [Retroperitoneal fibrosis].
AB  - Retroperitoneal fibrosis (RPF) is characterised by inflammatory fibrotic
      processes affecting the retroperitoneal structures. Its prevalence of 1 -
      2/200,000 makes it a rare disease. To date, there are no guidelines for the
      diagnosis of or therapy for the disease. If untreated, the disease may be fatal.
      In 2006, the Department of Urology of the HELIOS Klinikum Wuppertal undertook to
      establish a nationwide patient registry, which would facilitate prospective
      therapy trials and the drafting of recommendations for diagnostic procedures. The
      pathogenesis of the disease is still unclear. Since some RPF-patients present
      with associated autoimmune diseases, autoimmune processes are suspected to play a
      role in causing the disease. The presence of autoantibodies and histological
      similarities with vasculitis support this hypothesis. Following initial general
      symptoms, patients display localised symptoms (flank pain, leg oedema, abdominal
      discomfort), caused by the displacing effect of the fibrotic plaques. Laboratory
      tests show elevated ESR and C-reactive protein and in some cases a moderate
      anaemia. Histological examinations should be undertaken to rule out the presence
      of malignant tumours. Radiological diagnostics (excretory urography, CT, MRI)
      show a retroperitoneal mass which blocks, compresses and displaces, completely or
      in part, the large vessels and the ureter. Initial therapy aims at restoring the
      function of the affected hollow organs through the application of (ureteric)
      stents, followed by immunosuppressive therapy. If drug therapy is unsuccessful,
      surgical procedures will follow to protect the ureter from compression. In some
      cases, ureteral replacement or an autotransplant of the kidney may be necessary.
      Life-long observation of the patients is necessary, as the disease may be chronic
      and relapsing. Interdisciplinary and nationwide cooperation is of crucial
      importance to further investigate this disease.

PMID- 17516382
TI  - [Percutaneous nephrolithotomy - always effective and free of complications?].
AB  - PURPOSE: The purpose of this study was to evaluate the results and complications
      of percutaneous nephrolithotomies performed within 5 years in our patients.
      MATERIALS AND METHODS: From 2001 to 2005 in our department 158 percutaneous
      nephrolithotomies (PNL) in 131 patients and 138 renal units were performed. The
      indications for PNL were calculus greater than 2 cm, failed ESWL, and when there
      is additional urinary obstruction which was not caused by the stone itself. Data
      concerning past medical history, about the procedure including complications and
      the postoperative course were collected and evaluated. RESULTS: 87 (63 %) of the
      patients had a history of prior stones. The main symptoms were flank pain,
      recurrent renal colic and urinary tract infection. The stones treated had a size
      from 5 to 60 mm. In 40 patients (29 %) relief of urinary obstruction (double-J
      ureteral stent or percutaneous nephrostomy) or ESWL was performed prior to PNL.
      Mean operating time was 83 (30 - 235) minutes including retrograde placement of a
      ureteral catheter and nephrostomy. Complications occurred in 26 (16.5 %)
      procedures. Severe complications were: one fatal pulmonary embolism, one
      septicaemia, three open revisions (including one nephrectomy) and four blood
      transfusions for blood loss. In 94 patients (68 %) there was no residual stone or
      gravel after the first PNL. No further therapy was necessary in 17 (39 %) of the
      44 patients with incomplete stone removal. 19 patients underwent a secondary PNL.
      In these procedures the efficacy decreased. 102 of 131 patients (138 renal units
      = 73.9 %) were discharged without residual stone after 158 procedures.
      CONCLUSIONS: PNL is an efficient and rarely complicated procedure for larger
      stones of the upper urinary tract. Even so, the occurrence of severe
      complications must be considered. Complications can be minimised by the use of a
      standardised therapeutic pathway.

PMID- 17516383
TI  - [A thermodynamic study on bovine spermatozoa by microcalorimetry after Percoll
      density-gradient centrifugation - experimental probe of its utility in
      andrology].
AB  - PURPOSE: Microcalorimetric measurements can be used for recording exothermic or
      endothermic summation effects of a great variety of biological processes. The aim
      of the present study was to examine the usefullness of the microcalorimetry
      method to characterise the biological activity of spermatozoa. MATERIALS AND
      METHODS: The heat flow of bovine fresh sperm as well as cryosperm samples were
      measured after Percoll density-gradient centrifugation in a 4-channel
      microcalorimeter. Various calibration times, volumes of samples and sperm
      concentrations were tested and analysed. Sperm concentration was recorded by a
      computer-assisted, computer-aided software system method (CASA). RESULTS: Using a
      calibration time of 15 minutes, the heat signal of the fresh and cryosperm
      samples showed a characteristic peak after 39.5 min and 38.1 min (mean),
      respectively, with a significant correlation to sample volume and sperm
      concentration (p < 0.05). For obtaining the best results, a sample volume of 1 ml
      and a sperm concentration of more than 50 x 10 (6)/mL was used. CONCLUSIONS: With
      microcalorimetric measurements the biological activity of spermatozoa could be
      recorded for reproducible results, thus opening the way to an automatised
      ejaculate analysis in the future. More investigations are necessary to correlate
      microcalorimetric parameters with semen function.

PMID- 17516384
TI  - [Treatment errors involving diagnosis of and therapy for prostate carcinoma].
AB  - PURPOSE: In patients with prostate carcinoma diagnosis and therapy often present
      problems that are difficult to solve. Perfect results can only be reached by the
      highest level of professional expertise and required care. In cases of unwanted
      results and incidences it is asked whether claims of patients against their
      doctors are justified or not. METHODS: Claims of patients were reviewed by the
      commission of experts for medical mistakes of treatment of the state medical
      board of North Rhine based on objective criteria, out of court and free of
      charge. RESULTS: From 1975 to 1998 only 4 treatment errors were ascertained in
      patients with prostate carcinoma, 3 concerning the diagnosis and 1 concerning an
      operation. From 1999 to 2005 the errors of treatment increased by 6S-fold to 26.
      Mistakes concerned the diagnosis in 18 cases, the indication for operation in 1,
      the operative technique in 2 and the postoperative care in 5 cases. CONCLUSIONS:
      In comparison with the about 50,000 patients in whom a prostate carcinoma is
      diagnosed and treated in Germany every year the presented cases seem to be
      singular incidences. However, in the view of the experts, these are the tips of
      icebergs, since reviews most often are requested when professional disappointment
      and loss of confidence come together. This can only be avoided when the
      professionality and carefulness of the doctors is apparent and combined with
      their sympathy for their patients.

PMID- 17516385
TI  - [Mesonephroid carcinoma of the urinary bladder (clear cell carcinoma). Two case
      reports and review of the literature in a rare variation of the primary
      adenocarcinoma].
AB  - Mesonephroid adenocarcinoma of the bladder may be a malignant form of nephrogenic
      adenoma or nephroid metaplasia. The lesion is extremely rare in the urinary
      bladder, and to our knowledge 19 cases have been reported in the literature. We
      report two cases of mesonephroid adenocarcinoma of the bladder which were treated
      by radical cystectomy.

PMID- 17516386
TI  - [Penoscrotal elephantiasis].
AB  - Penoscrotal elephantiasis is not an uncommon clinical picture that may arise as a
      symptom of many diseases; it is usually a sequela of a recurring inflammatory
      process, eczema or malignancy. Elephantiasis often occurs after radical
      operations in the pelvic region. Displacement of lymphatic pathways leads to a
      local edema which over the course of time may lead to a considerable increase in
      volume of the patient's genitals or other affected parts. The diagnosis of
      elephantiasis is not difficult. It is much more difficult to determine which
      disease has caused the obstruction of the lymphatic pathways. If it is a
      reversible stage, the object of treatment is to remove the obstruction and
      reinstate the physiological lymph flow. Conservative measures such as
      administration of anti-inflammatory drugs and diuretics, physical measures such
      as baths, massage, elevation of the affected parts and treatment of the
      underlying disease may be considered. On progression to irreversible
      elephantiasis a chronic lymphatic edema occurs for which conservative measures
      will be unsuccessful. For cases where physical and anti-inflammatory measures are
      unsuccessful, excision and amputation of the affected penoscrotal region is
      recommended in order to eliminate the functional dysfunction. We report on two
      cases of penoscrotal elephantiasis, one in a child and the other in an adult man.

PMID- 17516387
TI  - [Retroperitoneal adrenalectomy].

PMID- 17516388
TI  - Actions to strengthen adult and adolescent immunization coverage in the United
      States: policy principles of the Infectious Diseases Society of America.

PMID- 17516389
TI  - Mixed fungemia: incidence, risk factors, and mortality in a general hospital.
AB  - BACKGROUND: Fungemia has been historically considered to be a disease caused by a
      single Candida species; the detection of >1 species of yeast in circulating blood
      was distinctly uncommon using traditional microbiological procedures. We describe
      episodes of mixed fungemia (MF), detected between 1985 and 2006, in a large
      teaching hospital. METHODS: The study was divided into 2 periods that were
      separated by the introduction, in January 2005, of the CHROmagar Candida medium
      (CHROMagar) for the routine subculturing of blood cultures in which yeast has
      been identified. Overall, we documented 747 cases of fungemia. During the first
      period (1985-1994), we identified 217 episodes of fungemia and no single episode
      of MF; during the second period (1995-2006), 15 episodes of MF were detected
      among 530 episodes of fungemia (2.8%). Candida albicans was isolated in 13
      patients, non-albicans species of Candida in 16 patients, and Saccharomyces
      cerevisiae in 1 patient. Each episode of MF was compared with 2 control episodes
      of monomicrobial fungemia. RESULTS: Patients with MF had more frequently
      experienced organ transplantation (13% vs. 0%) and surgery (60% vs. 27%), had
      less frequently received parenteral nutrition (40% vs. 70%) or had intravenous
      lines (80% vs. 100%), and had a lower incidence of shock (6% vs. 37%) and a lower
      mortality (20% vs. 53%). CONCLUSIONS: Despite the introduction of chromogenic
      agar, MF is still an uncommon disease and has a less severe outcome than does
      monomicrobial candidemia.

PMID- 17516390
TI  - Cryptococcal immune reconstitution inflammatory syndrome following alemtuzumab
      therapy.
AB  - Alemtuzumab is a lymphocyte ablative agent that may cause susceptibility to
      severe opportunistic infections similar to those seen in AIDS. Pathogen-specific
      immune reconstitution syndromes can complicate antiretroviral therapy and immune
      recovery in HIV-infected patients. We present the first reported case of immune
      reconstitution syndrome associated with T lymphocyte recovery after alemtuzumab
      therapy.

PMID- 17516391
TI  - Cidofovir and foscarnet for treatment of human herpesvirus 6 encephalitis in a
      neutropenic stem cell transplant recipient.
AB  - We report a stem cell transplant recipient who developed human herpesvirus 6
      encephalitis. Human herpesvirus 6 load indicated massive intrathecal viral
      replication. Administration of cidofovir followed by foscarnet was associated
      with total clearance of human herpesvirus 6 infection. Cidofovir and foscarnet
      combination therapy may be beneficial for reducing mortality of (neutropenic)
      stem cell transplant recipients with human herpesvirus 6 encephalitis.

PMID- 17516392
TI  - Toxic shock-like syndrome associated with staphylococcal enterocolitis in an HIV
      infected man.
AB  - A human immunodeficiency virus-infected individual developed severe secretory
      diarrhea due to infection with Staphylococcus aureus. When octreotide therapy was
      initiated, a toxic shock-like syndrome developed that was associated with fever,
      multisystem organ damage, and ultimately, desquamation of the palms and soles.
      The isolate was methicillin susceptible and produced enterotoxins B and C. This
      is, to our knowledge, the first reported case of toxic shock syndrome to develop
      secondary to staphylococcal enterocolitis in an adult.

PMID- 17516393
TI  - Executive summary--Actions to strengthen adult and adolescent immunization
      coverage in the United States: policy principles of the Infectious Diseases
      Society of America.

PMID- 17516394
TI  - Adult immunization: what can we learn from the childhood immunization program?

PMID- 17516395
TI  - Point: Vancomycin is not obsolete for the treatment of infection caused by
      methicillin-resistant Staphylococcus aureus.
AB  - Since the discovery, development, and US Food and Drug Administration approval of
      vancomycin in the 1950s, this agent has remained a mainstay for the treatment of
      infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However,
      because of the development of new antistaphylococcal antibiotics and reports of
      vancomycin failures, the utility of vancomycin has recently been questioned.
      Although vancomycin did not undergo the strict US Food and Drug Administration
      approval process that is in place today to demonstrate efficacy, there is
      considerable information available that sheds light on the role vancomycin has in
      infectious diseases pharmacotherapy today. In addition, although we look to in
      vitro susceptibility testing to assess vancomycin activity against S. aureus, we
      have come to appreciate that resistance of S. aureus to vancomycin can be a
      continuous--rather than a categorical--phenomenon. This has resulted in clinical
      microbiology laboratories having difficulty identifying S. aureus that may not
      respond to conventional doses of vancomycin. A better understanding is needed of
      the pharmacodynamic relationship between vancomycin and MRSA as relates to
      optimal dosing strategies, including consideration for loading doses, and
      development of rational categorical breakpoints for susceptibility based on
      clinical outcomes. By better understanding these critical issues, it may be
      possible to optimize the use of vancomycin, resulting in a cost-effective
      treatment option for many patients infected with MRSA.

PMID- 17516396
TI  - Counterpoint: Vancomycin and Staphylococcus aureus--an antibiotic enters
      obsolescence.
AB  - The efficacy of vancomycin for the treatment of patients with infections due to
      Staphylococcus aureus is impaired by its poor tissue penetration and by its
      relatively weak antibacterial activity--an activity that is declining as S.
      aureus evolves. Neither dose escalation nor use of vancomycin in combination with
      other antibiotics that have antistaphylcoccal activity has been demonstrated to
      safely enhance its therapeutic efficacy. Although no clinical trials suggest
      superiority of vancomycin over any comparator, some have provided evidence of its
      inferiority. Strong consideration should be given to the use of alternative
      agents in the treatment of serious S. aureus infections.

PMID- 17516397
TI  - Role of imiquimod and parenteral meglumine antimoniate in the initial treatment
      of cutaneous leishmaniasis.
AB  - BACKGROUND: Cutaneous leishmaniasis is a serious public health problem in the
      developing world. The main therapeutic agent--pentavalent antimony, developed >50
      years ago--is expensive, often accompanied by severe adverse effects, and
      complicated by the emergence of drug resistance. Better therapies are urgently
      needed. In the present pilot study, we compared the use of imiquimod, an
      immunomodulatory molecule, to the use of meglumine antimoniate alone and in
      combination for the initial treatment of cutaneous leishmaniasis. MATERIALS AND
      METHODS: Patients with newly diagnosed cutaneous leishmaniasis were enrolled from
      a single referral center in Lima, Peru, from August 2005 through October 2005.
      Patients were randomly assigned to 1 of 3 treatment groups and received either
      imiquimod 7.5% cream administered topically every other day for 20 days,
      intravenous meglumine antimoniate administered at a dosage of 20 mg/kg per day
      every day for 20 days, or combination therapy with both intravenous meglumine
      antimoniate and imiquimod 7.5% cream. Patients were evaluated weekly and at 1 and
      3 months after treatment. Patients who had healed lesions at 3 months were
      considered to be clinically cured. RESULTS: Although several patients showed
      initial resolution of symptoms with imiquimod treatment alone, all of these
      patients experienced relapse after treatment discontinuation. Four (57%) of 7
      patients treated with meglumine antimoniate alone and 7 (100%) of 7 patients
      treated with combination therapy were cured. Combination therapy was not only
      more effective than the other 2 treatments (P<.05) but also led to faster healing
      and better cosmetic results. CONCLUSION: Combination therapy with imiquimod and
      meglumine antimoniate is a promising regimen for the initial treatment of
      cutaneous leishmaniasis that warrants additional larger studies.

PMID- 17516398
TI  - Evaluation of the management of postoperative aseptic meningitis.
AB  - BACKGROUND: A consensus conference recommended empirical antibiotic therapy for
      all patients with postoperative meningitis and treatment withdrawal after 48 or
      72 h if cerebrospinal fluid culture results are negative. However, this approach
      is not universally accepted and has not been assessed in clinical trials.
      METHODS: We performed a cohort study of all patients who received a diagnosis of
      postoperative meningitis from January 1998 through May 2005 in a teaching
      hospital. From January 1998 through September 2003 (control period), guidelines
      were lacking or were not implemented. From October 2003 through May 2005
      (interventional period), all patients received a predefined intravenous
      antibiotic therapy that was discontinued on the third day if the meningitis was
      considered aseptic. Clinical outcome and duration of antibiotic therapy were
      analyzed for each patient. RESULTS: Seventy-five episodes of postoperative
      meningitis (21 cases of bacterial meningitis and 54 cases of aseptic meningitis)
      were investigated. Patients with aseptic meningitis received antibiotic treatment
      for a mean +/- standard deviation duration of 11+/-5 days during the control
      period and 3.5+/-2 days during the intervention period (P=.001). The duration of
      antibiotic treatment for bacterial meningitis was not significantly different
      between the 2 periods. All episodes of bacterial and aseptic meningitis were
      cured, and complications were rare during both periods. CONCLUSIONS: Stopping
      antibiotic treatment after 3 days is effective and safe for patients with
      postoperative meningitis whose cerebrospinal fluid culture results are negative.

PMID- 17516399
TI  - Fever in returned travelers: results from the GeoSentinel Surveillance Network.
AB  - BACKGROUND: Fever is a marker of potentially serious illness in returned
      travelers. Information about causes of fever, organized by geographic area and
      traveler characteristics, can facilitate timely, appropriate treatment and
      preventive measures. METHODS: Using a large, multicenter database, we assessed
      how frequently fever is cited as a chief reason for seeking medical care among
      ill returned travelers. We defined the causes of fever by place of exposure and
      traveler characteristics. RESULTS: Of 24,920 returned travelers seen at a
      GeoSentinel clinic from March 1997 through March 2006, 6957 (28%) cited fever as
      a chief reason for seeking care. Of patients with fever, 26% were hospitalized
      (compared with 3% who did not have fever); 35% had a febrile systemic illness,
      15% had a febrile diarrheal disease, and 14% had fever and a respiratory illness.
      Malaria was the most common specific etiologic diagnosis, found in 21% of ill
      returned travelers with fever. Causes of fever varied by region visited and by
      time of presentation after travel. Ill travelers who returned from sub-Saharan
      Africa, south-central Asia, and Latin America whose reason for travel was
      visiting friends and relatives were more likely to experience fever than any
      other group. More than 17% of travelers with fever had a vaccine-preventable
      infection or falciparum malaria, which is preventable with chemoprophylaxis.
      Malaria accounted for 33% of the 12 deaths among febrile travelers. CONCLUSIONS:
      Fever is common in ill returned travelers and often results in hospitalization.
      The time of presentation after travel provides important clues toward
      establishing a diagnosis. Preventing and promptly treating malaria, providing
      appropriate vaccines, and identifying ways to reach travelers whose purpose for
      travel is visiting friends and relatives in advance of travel can reduce the
      burden of travel-related illness.

PMID- 17516400
TI  - Changing characteristics of invasive pneumococcal disease in Metropolitan
      Atlanta, Georgia, after introduction of a 7-valent pneumococcal conjugate
      vaccine.
AB  - BACKGROUND: The rate of invasive pneumococcal disease (IPD) has decreased among
      both immunized children and nonimmunized adults since the licensure of a
      heptavalent pneumococcal conjugate vaccine (PCV7) for use in infants in the
      United States in 2000. METHODS: Temporal trends in IPD incidence, clinical
      syndromes, and underlying conditions were analyzed using active laboratory- and
      population-based surveillance data from the Centers for Disease Control and
      Prevention-sponsored Georgia Emerging Infections Program for the 20-county
      Metropolitan Atlanta, Georgia, for the period of July 1997 through June 2004. P
      values were determined by test for trend. RESULTS: Since 2000, there have been
      significant decreases in the rates of invasive pneumococcal pneumonia (relative
      risk [RR], 0.80; P=.002) and meningitis (RR, 0.41; P=.003) in adults and for
      primary bacteremia, invasive pneumonia, and meningitis in children (RR, 0.16
      [P<.001], 0.60 [P=.003], and 0.70 [P=.009], respectively). Among human
      immunodeficiency virus-infected persons, there were significant decreases in the
      overall rates of IPD (decrease of 43%; P<.001) and invasive pneumonia (decrease
      of 44%; P<.001) since 2000-2001, although the rate of IPD increased significantly
      (increase of 53%; P=.022) among patients with acquired immunodeficiency syndrome.
      There was a concurrent increase in the proportion of adults aged > or = 40 years
      with underlying comorbidities. Rates of non-PCV7 serotypes increased 1.61-fold
      and 1.28-fold from 2000-2001 to 2003-2004 in children and adults (P=.005 for
      both). CONCLUSIONS: The decreasing incidence of IPD in Atlanta since 2000-2001
      was associated with decreases in cases of pneumonia and meningitis in adult and
      pediatric subjects and in cases of primary bacteremia in children. The burden of
      serotype-replacement disease remained small. Adults with comorbidities represent
      a growing proportion of patients with IPD.

PMID- 17516401
TI  - An outbreak of multidrug-resistant Acinetobacter baumannii-calcoaceticus complex
      infection in the US military health care system associated with military
      operations in Iraq.
AB  - BACKGROUND: We investigated an outbreak of multidrug-resistant Acinetobacter
      baumannii-calcoaceticus complex infection among US service members injured in
      Iraq. METHODS: The investigation was conducted in Iraq and Kuwait, in the 2
      military hospitals where the majority of injured service members were initially
      treated. After initially characterizing the outbreak, we evaluated 3 potential
      sources of infection for the period March 2003 to December 2004. The evaluation
      included screening samples that were obtained from the skin of patients for the
      presence of colonization and assessing the soil and health care environments for
      the presence of A. baumanii-calcoaceticus complex organisms. Isolates obtained
      from samples from patients in US Military treatment facilities, as well as
      environmental isolates, were genotypically characterized and compared using
      pulsed-field gel electrophoresis. RESULTS: A. baumanii-calcoaceticus complex
      organisms were present on the skin in only 1 (0.6%) of 160 patients who were
      screened and in 1 (2%) of 49 soil samples. A. baumanii-calcoaceticus complex
      isolates were recovered from treatment areas in 7 of the 7 field hospitals
      sampled. Using pulsed-field gel electrophoresis, we identified 5 cluster groups
      in which isolates from patients were related to environmental isolates. One
      cluster included hospitalized patients who had not been deployed to Iraq. Among
      the clinical isolates, only imipenem, polymyxin B, and colistin demonstrated
      reliable in vitro antimicrobial activity. Generally, the environmental isolates
      were more drug susceptible than were the clinical isolates. CONCLUSIONS: Our
      findings suggest that environmental contamination of field hospitals and
      infection transmission within health care facilities played a major role in this
      outbreak. On the basis of these findings, maintaining infection control
      throughout the military health care system is essential. Novel strategies may be
      required to prevent the transmission of pathogens in combat field hospitals.

PMID- 17516402
TI  - Infective endocarditis due to penicillin-resistant viridans group streptococci.
AB  - BACKGROUND: The emergence of viridans group streptococci that are relatively or
      fully resistant to penicillin is increasingly being recognized worldwide, but
      only a scant number of penicillin-resistant isolates have been described as a
      cause of infective endocarditis. Because of the paucity of data, it has been
      difficult to define optimal treatment regimens for this syndrome. Thus,
      recommendations for therapy have largely been made on the basis of consensus
      opinion. METHODS: We retrospectively identified a cohort of patients with
      infective endocarditis due to penicillin-resistant viridans group streptococci
      who were seen at the Mayo Clinic (Rochester, MN) between January 1967 and April
      2006. Demographic characteristics, clinical features, treatment regimens, and
      outcomes were analyzed. Mean values are shown with standard deviations. RESULTS:
      Twenty-nine patients were identified over the 38.5-year study period. Nineteen
      patients with native valve endocarditis were cured; 9 of these 19 patients
      received a 2.3+/-0.4-week antibiotic regimen consisting of penicillin and an
      aminoglycoside, and 8 of these 19 patients received treatment courses of 5.1+/
      1.4 weeks' duration that consisted of either a bimodal combination regimen with a
      penicillin or ceftriaxone and an aminoglycoside or ceftriaxone monotherapy. Nine
      of 10 patients with prosthetic valve infection were cured with 4.1+/-0.6-week
      regimens that consisted of either a combination regimen or monotherapy with
      vancomycin or ceftriaxone. Mean duration of follow-up after hospital discharge
      was 9.1 years. CONCLUSIONS: Outcomes of this relatively large population of
      patients with endocarditis with a prolonged duration of follow-up indicate that
      the application of current treatment guidelines should be successful in most
      patients.

PMID- 17516403
TI  - Low mannose-binding lectin concentration is associated with severe infection in
      patients with hematological cancer who are undergoing chemotherapy.
AB  - BACKGROUND: Mannose-binding lectin (MBL) is a serum lectin involved in innate
      immune response. Low serum MBL concentration may constitute a risk factor for
      infection in patients receiving myelosuppressive chemotherapy. METHODS: We
      conducted a prospective, observational study that assessed MBL concentration as a
      risk factor for infection in patients with hematological malignancy who were
      hospitalized to undergo at least 1 chemotherapy cycle. MBL deficiency was defined
      using an algorithm that considered the serum MBL concentration and the MBL
      genotype. The primary end point was the ratio of duration of febrile neutropenia
      to the duration of neutropenia. Secondary end points included the incidence of
      severe infection (e.g., sepsis, pneumonia, bacteremia, and invasive fungal
      infection). Logistic regression analysis was conducted, and Fisher's exact test
      was used to analyze binary outcomes, and Kaplan-Meier estimates and log rank
      tests were used for time-to-event variables. RESULTS: We analyzed 255 patients
      who received 569 cycles of chemotherapy. The median duration of neutropenia per
      cycle was 7 days (interquartile range, 0-13 days). Sixty-two patients (24%) were
      found to have MBL deficiency. Febrile neutropenia occurred at least once in 200
      patients. No difference in the primary outcome was seen. The incidence of severe
      infection was higher among MBL-deficient patients than among non-MBL-deficient
      patients (1.96 vs. 1.34 cases per 100 days for analysis of all patients [P=.008]
      and 1.85 vs. 0.94 cases per 100 days excluding patients with acute leukemia
      [P<.001]). CONCLUSIONS: MBL deficiency does not predispose adults with
      hematological cancer to more-frequent or more-prolonged febrile episodes during
      myelosuppressive chemotherapy, but MBL-deficient patients have a greater number
      of severe infections and experience their first severe infection earlier,
      compared with nondeficient patients.

PMID- 17516404
TI  - Clinical use of polymerase chain reaction performed on peripheral blood and bone
      marrow samples for the diagnosis and monitoring of visceral leishmaniasis in HIV
      infected and HIV-uninfected patients: a single-center, 8-year experience in Italy
      and review of the literature.
AB  - BACKGROUND: To overcome some of the limitations of conventional microbiologic
      techniques, polymerase chain reaction (PCR)-based assays are proposed as useful
      tools for the diagnosis of visceral leishmaniasis. PATIENTS AND METHODS: A
      comparative study using conventional microbiologic techniques (i.e., serologic
      testing, microscopic examination, and culture) and a Leishmania species-specific
      PCR assay, using peripheral blood and bone marrow aspirate samples as templates,
      was conducted during an 8-year period. The study cohort consisted of 594 Italian
      immunocompetent (adult and pediatric) and immunocompromised (adult) patients
      experiencing febrile syndromes associated with hematologic alterations and/or
      hepatosplenomegaly. Identification of the infecting protozoa at the species level
      was directly obtained by PCR of peripheral blood samples, followed by restriction
      fragment-length polymorphism analysis of the amplified products, and the results
      were compared with those of isoenzyme typing of Leishmania species strains from
      patients, which were isolated in vitro. RESULTS: Sixty-eight patients (11.4%) had
      a confirmed diagnosis of visceral leishmaniasis. Eleven cases were observed in
      human immunodeficiency virus (HIV)-uninfected adults, 20 cases were observed in
      HIV-infected adults, and the remaining 37 cases were diagnosed in HIV-uninfected
      children. In the diagnosis of primary visceral leishmaniasis, the sensitivities
      of the Leishmania species-specific PCR were 95.7% for bone marrow aspirate
      samples and 98.5% for peripheral blood samples versus sensitivities of 76.2%,
      85.5%, and 90.2% for bone marrow aspirate isolation, serologic testing, and
      microscopic examination of bone marrow biopsy specimens, respectively. None of
      229 healthy blood donors or 25 patients with imported malaria who were used as
      negative control subjects had PCR results positive for Leishmania species in
      peripheral blood samples (i.e., specificity of Leishmania species-specific PCR,
      100%). PCR and restriction fragment-length polymorphism analysis for Leishmania
      species identification revealed 100% concordance with isoenzyme typing in the 19
      patients for whom the latter data were available. CONCLUSIONS: PCR assay is a
      highly sensitive and specific tool for the diagnosis of visceral leishmaniasis in
      both immunocompetent and immunocompromised patients and can be reliably used for
      rapid parasite identification at the species level.

PMID- 17516405
TI  - Characterization of invasive Haemophilus influenzae disease in Manitoba, Canada,
      2000-2006: invasive disease due to non-type b strains.
AB  - In addition to the proportional increase in cases of non-type b Haemophilus
      influenzae disease in the post-H. influenzae type b vaccine era, the incidence of
      invasive H. influenzae disease was found to be approaching the rates of H.
      influenzae type b disease that were documented in the prevaccine period. Fifty
      six percent of invasive disease now occurs in individuals aged >10 years.

PMID- 17516406
TI  - An immigrant with a painful swelling in his back.

PMID- 17516407
TI  - The long-term outcomes of human West Nile virus infection.
AB  - Since its introduction to North America in 1999, human infection with West Nile
      virus (WNV) has resulted in considerable acute morbidity and mortality. Although
      the ongoing epidemic has resulted in a great increase in our understanding of the
      acute clinical features of human illness and helped to define associated clinical
      syndromes, far less is known about potential long-term clinical and functional
      sequelae. Several recent assessments, however, suggest that patients--even those
      with apparently mild cases of acute disease--frequently have subjective, somatic
      complaints following WNV infection. Persistent movement disorders, cognitive
      complaints, and functional disability may occur after West Nile neuroinvasive
      disease. West Nile poliomyelitis may result in limb weakness and ongoing
      morbidity that is likely to be long term. Although further assessment is needed,
      the long-term neurological and functional sequelae of WNV infection are likely to
      represent a considerable source of morbidity in patients long after their
      recovery from acute illness.

PMID- 17516408
TI  - Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a
      population-based cohort study.
AB  - BACKGROUND: There are concerns about highly active antiretroviral therapy (HAART)
      causing a progressive increase in the risk of ischemic heart disease. We examined
      this issue in a nationwide cohort study of patients with human immunodeficiency
      virus (HIV) infection and a population-based control group. METHODS: We
      determined the rate of first hospitalization for ischemic heart disease in all
      Danish patients with HIV infection (3953 patients) from 1 January 1995 through 31
      December 2004 and compared this rate with that for 373,856 subjects in a
      population-based control group. Data on first hospitalization for ischemic heart
      disease and comorbidity were obtained from the Danish National Hospital Registry
      for all study participants. We used Cox's regression to compute the
      hospitalization rate ratio as an estimate of relative risk, adjusting for
      comorbidity. RESULTS: Although the difference was not statistically significant,
      patients with HIV infection who had not initiated HAART were slightly more likely
      to be hospitalized for the first time with ischemic heart disease than were
      control subjects (adjusted relative risk, 1.39; 95% confidence interval, 0.81
      2.33). After HAART initiation, the risk increase became substantially higher
      (adjusted relative risk, 2.12; 95% confidence interval, 1.62-2.76), but the
      relative risk did not further increase in the initial 8 years of HAART.
      CONCLUSIONS: Compared with the general population, HIV-infected patients
      receiving HAART have an increased risk of ischemic heart disease, but the
      relative risk is stable up to 8 years after treatment initiation.

PMID- 17516409
TI  - Lung fluid immunoglobulin from HIV-infected subjects has impaired opsonic
      function against pneumococci.
AB  - BACKGROUND: The incidence of pneumococcal pneumonia is greatly increased among
      human immunodeficiency virus (HIV)-infected subjects, compared with among non-HIV
      infected subjects. Lung fluid levels of immunoglobulin G (IgG) specific for
      pneumococcal capsular polysaccharide are not reduced in HIV-infected subjects;
      therefore, we examined immunoglobulin subtypes and compared lung fluid IgG
      opsonic function in HIV-infected subjects with that in healthy subjects. METHODS:
      Bronchoalveolar lavage (BAL) fluid and serum samples were collected from 23 HIV
      infected and 26 uninfected subjects. None of the subjects were receiving highly
      active antiretroviral therapy, and none had received pneumococcal vaccination.
      Pneumococcal capsule-specific IgG levels in serum and BAL fluid were measured by
      enzyme-linked immunosorbent assay, and IgG was concentrated from 40 mL of BAL
      fluid. Opsonization and opsonophagocytosis of pneumococci with serum, BAL fluid,
      and BAL IgG were compared between HIV-infected subjects and healthy subjects.
      RESULTS: The effect of type 1 pneumococcal capsular polysaccharide-specific IgG
      in opsonizing of pneumococci was significantly less using both serum and BAL IgG
      from HIV-infected subjects, compared with serum and BAL IgG from healthy subjects
      (mean level, 8.9 fluorescence units [95% confidence interval, 8.1-9.7
      fluorescence units] vs. 12.1 fluorescence units [95% confidence interval, 9.7
      15.2 fluorescence units]; P=.002 for lung BAL IgG). The opsonophagocytosis of
      pneumococci observed using BAL IgG from HIV-infected subjects was significantly
      less than that observed using BAL IgG from healthy subjects (37 fluorescence
      units per ng of IgG [95% confidence interval, 25-53 fluorescence units per ng of
      IgG] vs. 127 fluorescence units per ng of IgG [95% confidence interval, 109-145
      fluorescence units per ng of IgG]; P<.001). CONCLUSION: HIV infection is
      associated with decreased antipneumococcal opsonic function in BAL fluid and
      serum.

PMID- 17516410
TI  - Clinical, immunological, and epidemiological importance of antituberculosis T
      cell responses in HIV-infected Africans.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-associated tuberculosis is a major
      cause of mortality in Africa. The assay of T cell interferon- gamma released in
      response to antigens of greater specificity than purified protein derivative is a
      useful improvement over the Mantoux tuberculin skin test, but few studies have
      evaluated interferon-gamma secretion in HIV-infected individuals. METHODS:
      Mycobacterium tuberculosis antigen-specific interferon-gamma secretion was
      assessed by whole blood assay and enzyme-linked immunospot, which were compared
      with the Mantoux tuberculin skin test in HIV-infected and HIV-uninfected
      individuals without active tuberculosis and HIV-infected patients with pulmonary
      tuberculosis in Khayelitsha, South Africa. RESULTS: The skin test and whole blood
      assay responses to purified protein derivative in HIV-positive subjects were
      decreased, compared with responses in HIV-negative subjects (P < .001). By
      contrast, the responses to M. tuberculosis antigens (early secreted antigenic
      target 6, culture filtrate protein 10, TB10.3, and alpha-crystallin 2) were less
      affected, indicating a high prevalence of latent tuberculosis (approximately 80%)
      in both HIV-negative and HIV-positive subject groups. Whole blood assay responses
      did not differ between the HIV-positive subjects without tuberculosis and HIV
      positive subjects with tuberculosis, but the enzyme-linked immunospot method
      response to early secreted antigenic target 6 and culture filtrate protein 10 was
      higher in the group of HIV-infected subjects with tuberculosis (P < or = .04),
      although this group had lower CD4+ cell counts. A ratio of the combined enzyme
      linked immunospot method response divided by the CD4+ cell count of > 1.0 had 88%
      sensitivity and 80% specificity for active pulmonary tuberculosis in HIV-infected
      individuals. CONCLUSIONS: Interferon-gamma release appears to be less impaired
      than skin testing by HIV coinfection. The novel potential to relate the enzyme
      linked immunospot method and CD4+ cell count to assist diagnosis of active
      tuberculosis in patients with HIV infection is important and deserves further
      evaluation.

PMID- 17516411
TI  - Time to undetectable viral load after highly active antiretroviral therapy
      initiation among HIV-infected pregnant women.
AB  - BACKGROUND: There have been no clinical trials in resource-rich regions that have
      addressed the question of which highly active antiretroviral therapy (HAART)
      regimens are more effective for optimal viral response in antiretroviral-naive,
      human immunodeficiency virus (HIV)-infected pregnant women. METHODS: Data on 240
      HIV-1-infected women starting HAART during pregnancy who were enrolled in the
      prospective European Collaborative Study from 1997 through 2004 were analyzed. An
      interval-censored survival model was used to assess whether factors, including
      type of HAART regimen, race, region of birth, and baseline immunological and
      virological status, were associated with the duration of time necessary to
      suppress viral load below undetectable levels before delivery of a newborn.
      RESULTS: Protease inhibitor-based HAART was initiated in 156 women (65%), 125
      (80%) of whom received nelfinavir, and a nevirapine-based regimen was initiated
      in the remaining 84 women (35%). Undetectable viral loads were achieved by 73% of
      the women by the time of delivery. Relative hazards of time to achieving viral
      suppression were 1.54 (95% confidence interval, 1.05-2.26) for nevirapine-based
      HAART versus PI-based regimens and 1.90 (95% confidence interval, 1.16-3.12) for
      western African versus non-African women. The median duration of time from HAART
      initiation to achievement of an undetectable viral load was estimated to be 1.4
      times greater in women receiving PI-based HAART, compared with women receiving
      nevirapine-based HAART. Baseline HIV RNA load was also a significant predictor of
      the rapidity of achieving viral suppression by delivery, but baseline immune
      status was not. CONCLUSIONS: In this study, nevirapine-based HAART (compared with
      PI [mainly nelfinavir]-based HAART), western African origin, and lower baseline
      viral load were associated with shorter time to achieving viral suppression.

PMID- 17516415
TI  - Methicillin-resistant Staphylococcus aureus infections in sex partners: what is a
      sexually transmitted disease?

PMID- 17516416
TI  - To genotype or not to genotype: toward an optimal tailoring of treatment of
      chronic hepatitis B.

PMID- 17516417
TI  - Halo sign and improved outcome.

PMID- 17516418
TI  - Zanamivir treatment is equally effective for both influenza A and influenza B.

PMID- 17516412
TI  - Use of peripheral blood DNA for genotype antiretroviral resistance testing in
      drug-naive HIV-infected subjects.
AB  - Parallel analysis of peripheral blood mononuclear cell DNA and plasma RNA from
      169 drug-naive human immunodeficiency virus-infected subjects revealed that
      evaluation of both compartments increases the sensitivity of detection of drug
      resistance-related mutations, compared with examination of either source alone.
      Peripheral blood mononuclear cell DNA may play a role in the surveillance of
      transmitted antiretroviral resistance.

PMID- 17516420
TI  - Cultured articular chondrocytes sheets for partial thickness cartilage defects
      utilizing temperature-responsive culture dishes.
AB  - The extracellular matrix (ECM) of articular cartilage has several functions that
      are unique to joints. Although a technique for transplanting cultured
      chondrocytes has already been introduced, it is difficult to collect intact ECM
      when using enzymes to harvest samples. Temperature-responsive culture dishes have
      already been clinically applied in the fields of myocardial and corneal
      transplantation. Earlier studies have shown that a sheet of cultured cells with
      intact ECM and adhesive factors can be harvested using such culture dishes, which
      allow the surface properties of the dish to be reversibly altered by changing the
      temperature. Human chondrocytes were subjected to enzymatic digestion and then
      were seeded in temperature-responsive culture dishes. A sheet of chondrocytes was
      harvested by only reducing the temperature after the cultured cells reached
      confluency. A real-time PCR analysis of the chondrocyte sheets confirmed that
      type II collagen, aggrecan, and fibronectin were present. These results suggested
      that, although chondrocytes undergo dedifferentiation in a monolayer culture,
      multilayer chondrocyte sheets grown in a similar environment to that of three
      dimensional culture may be able to maintain a normal phenotype. A histological
      examination suggested that multilayer chondrocyte sheets could thus prevent the
      loss of proteoglycans because the area covered by the sheets was well stained by
      safranin-O. The present experiments suggested that temperature-responsive culture
      dishes are useful for obtaining cultured chondrocytes, which may then be
      clinically employed as a substitute for periosteal patches because such sheets
      can be applied without a scaffold.

PMID- 17516421
TI  - Adaptive features of aquatic mammals' eye.
AB  - The eye of aquatic mammals demonstrates several adaptations to both underwater
      and aerial vision. This study offers a review of eye anatomy in four groups of
      aquatic animals: cetaceans (toothed and baleen whales), pinnipeds (seals, sea
      lions, and walruses), sirenians (manatees and dugongs), and sea otters. Eye
      anatomy and optics, retinal laminar morphology, and topography of ganglion cell
      distribution are discussed with particular reference to aquatic specializations
      for underwater versus aerial vision. Aquatic mammals display emmetropia (i.e.,
      refraction of light to focus on the retina) while submerged, and most have
      mechanisms to achieve emmetropia above water to counter the resulting aerial
      myopia. As underwater vision necessitates adjusting to wide variations in
      luminosity, iris muscle contractions create species-specific pupil shapes that
      regulate the amount of light entering the pupil and, in pinnipeds, work in
      conjunction with a reflective optic tapetum. The retina of aquatic mammals is
      similar to that of nocturnal terrestrial mammals in containing mainly rod
      photoreceptors and a minor number of cones (however, residual color vision may
      take place). A characteristic feature of the cetacean and pinniped retina is the
      large size of ganglion cells separated by wide intercellular spaces. Studies of
      topographic distribution of ganglion cells in the retina of cetaceans revealed
      two areas of ganglion cell concentration (the best-vision areas) located in the
      temporal and nasal quadrants; pinnipeds, sirenians, and sea otters have only one
      such area. In general, the visual system of marine mammals demonstrates a high
      degree of development and several specific features associated with adaptation
      for vision in both the aquatic and aerial environments.

PMID- 17516423
TI  - Stomach anatomy and use in defining systemic relationships of the Cetacean family
      Ziphiidae (beaked whales).
AB  - Members of the Cetacean family Ziphiidae (Beaked whales) exhibit surprising
      diversity in stomach anatomy, particularly in the number of connecting chambers
      between the main and pyloric stomachs. Sixty-one stomachs of five beaked whale
      species were examined, including Berardius, Hyperoodon, Mesoplodon, Tasmacetus,
      and Ziphius. Specimens were obtained post mortem from beach-stranded individuals,
      with the exception of 30 Berardius specimens that were taken at a whaling station
      in Japan. Most specimens were collected by the Marine Mammal Program of the
      National Museum of Natural History, with the exception of one specimen of
      Mesoplodon steinegeri, which from the Los Angeles County Museum and one specimen
      of Tasmacetus from the Museum of New Zealand. Additional data are included from
      published accounts. A single species was examined for all of the genera but
      Mesoplodon, where there was material for 7 of 13 known species. The sample of
      Berardius bairdii was sufficient (n = 30) to determine species-specific variation
      in compartment counts. Chamber anatomy was explored by means of manual palpation.
      Results indicate that ziphiid stomachs can be separated into at least three
      principal groups: generalized ziphiid stomach (one main stomach, one pyloric
      stomach), derived stomach type I (two main stomachs, one pyloric stomach), and
      derived stomach type II (two main stomachs, two pyloric stomachs). Generalized
      stomachs are found in Hyperoodon, Tasmacetus, Ziphius, Mesoplodon densirostris,
      M. perrini, and M. stejnegeri. Derived stomachs of type I are found in Berardius,
      and of type II are found in Mesoplodon bidens, M. europaeus, and M. mirus. The
      ziphiids clearly form a distinct group of cetaceans in their utilization of
      differences in stomach morphology. These anatomical differences may serve to
      elucidate systematic relationships among the ziphiids. Further study is necessary
      to establish whether these differences correlate with specialized adaptations
      related to an aquatic environment.

PMID- 17516424
TI  - Structure of the integument of southern right whales, Eubalaena australis.
AB  - Skin (integument) anatomy reflects adaptations to particular environments. It is
      hypothesized that cetacean (whale) integument will show unique anatomical
      adaptations to an aquatic environment, particularly regarding differences in
      temperature, density, and pressure. In this study, the gross and histological
      structure of the southern right whale integument is described and compared with
      terrestrial mammals and previous descriptions of mysticete (baleen whale) and
      odontocete (toothed whale) species. Samples were taken of the integument of 98
      free-swimming southern right whales, Eubalaena australis, and examined by both
      light and electron microscopy. Results show that three epidermal layers are
      present, with the stratum corneum being parakeratotic in nature. As in bowhead
      whales, southern right whales possess an acanthotic epidermis and a notably thick
      hypodermis, with epidermal rods and extensive papillomatosis. However, unlike
      bowhead whales, southern right whales possess an uninterrupted hypodermal layer.
      Surprisingly, the integument of balaenids (right and bowhead mysticetes) in
      general is more like that of odontocetes than that of the more closely related
      balaenopterids (rorqual mysticetes). Similarities to odontocetes were found
      specifically in the collagen fibers in a fat-free zone of the reticular dermal
      layer and the elastic fibers in the dermal and hypodermal layers. Callosities, a
      distinctive feature of this genus, have a slightly thicker stratum corneum and
      are usually associated with hairs that have innervated and vascularized
      follicles. These hairs may function as vibrissae, thus aiding in aquatic foraging
      by allowing rapid detection of changes in prey density. Although the thick
      insulatory integument makes right whales bulky and slow-moving, it is an
      adaptation for living in cold water. Epidermal thickness, presence of epidermal
      rods, and callosities may act as barriers against mechanical injury from bodily
      contact with conspecifics or hard surfaces in the environment (e.g., rocks, ice).

PMID- 17516425
TI  - Co-determination of ATP and proteins in Triton X 100 non-ionic detergent-opened
      monolayer cultured cells.
AB  - Human monolayer cells (HEp-2 and Hep G2) were cultured in 96-well plates. A
      modified Triton X 100 nonionic detergent extraction method was used for releasing
      intracellular ATP and protein in one step. The detergent technique was compared
      to perchloric acid (PCA) extraction. ATP was determined by the firefly
      bioluminescence method and ATP values were referred to cell protein (ATP:protein
      ratio). There was no significant difference in ATP data between detergent and PCA
      treatments. The ATP:protein ratio seems to be a sensitive tool for characterizing
      the metabolic activity of monolayer tissue culture cells. The protein-mobilizing
      capability of Triton X 100 depends on the type of cell culture used. Our modified
      extraction gives reliable ATP:protein values with one simple extraction step.

PMID- 17516426
TI  - Stochastic simulation of physicochemical processes performance over supported
      metal nanoparticles.
AB  - The statistical lattice model has been proposed which permits one to take into
      account the change in the shape and surface morphology of the nanoparticle under
      the influence of the reaction media. The influence of monomolecular and
      dissociative adsorption on the particles equilibrium shape and surface morphology
      has been studied. It has been shown that by taking into account of attraction
      "adsorbate-metal" the reshaping of the initial hemispheric particle into cone
      shaped one occurs induced by adsorption, similar to the experimentally observed
      reversible reshaping of active nanoparticles. The model reaction A+B(2) has been
      studied taking into account the roughening of the active particle surface and the
      spillover phenomena of the adsorbed A(ads) species over the support surface.

PMID- 17516427
TI  - Shapelets: possibilities and limitations of shape-based virtual screening.
AB  - Complementarity of molecular surfaces is crucial for molecular recognition. A
      method for representation of molecular shape is presented. We decompose the
      molecular surface into commensurate patches with defined shape by fitting
      hyperbolical paraboloids onto a triangulated isosurface of the Gaussian model of
      a molecule. As a result of this decomposition we obtain a 3D graph representation
      of the molecular shape, which can be used for complete and partial shape matching
      and isosteric group searching. To point out the possibilities and limitations of
      shape-only models, we challenged our method by three scenarios in a virtual
      screening contest: rigid body alignment, consensus shape filtering, and target
      specific screening.

PMID- 17516428
TI  - Examination of the three-dimensional geometry of cetacean flukes using computed
      tomography scans: hydrodynamic implications.
AB  - The flukes of cetaceans function in the hydrodynamic generation of forces for
      thrust, stability, and maneuverability. The three-dimensional geometry of flukes
      is associated with production of lift and drag. Data on fluke geometry were
      collected from 19 cetacean specimens representing eight odontocete genera
      (Delphinus, Globicephala, Grampus, Kogia, Lagenorhynchus, Phocoena, Stenella,
      Tursiops). Flukes were imaged as 1 mm thickness cross-sections using X-ray
      computer-assisted tomography. Fluke shapes were characterized quantitatively by
      dimensions of the chord, maximum thickness, and position of maximum thickness
      from the leading edge. Sections were symmetrical about the chordline and had a
      rounded leading edge and highly tapered trailing edge. The thickness ratio
      (maximum thickness/chord) among species increased from insertion on the tailstock
      to a maximum at 20% of span and then decreasing steadily to the tip. Thickness
      ratio ranged from 0.139 to 0.232. These low values indicate reduced drag while
      moving at high speed. The position of maximum thickness from the leading edge
      remained constant over the fluke span at an average for all species of 0.285
      chord. The displacement of the maximum thickness reduces the tendency of the flow
      to separate from the fluke surface, potentially affecting stall patterns.
      Similarly, the relatively large leading edge radius allows greater lift
      generation and delays stall. Computational analysis of fluke profiles at 50% of
      span showed that flukes were generally comparable or better for lift generation
      than engineered foils. Tursiops had the highest lift coefficients, which were
      superior to engineered foils by 12-19%. Variation in the structure of cetacean
      flukes reflects different hydrodynamic characteristics that could influence
      swimming performance.

PMID- 17516429
TI  - Vertebral anatomy in the Florida manatee, Trichechus manatus latirostris: a
      developmental and evolutionary analysis.
AB  - The vertebral column of the Florida manatee presents an unusual suite of
      morphological traits. Key among these are a small precaudal count, elongate
      thoracic vertebrae, extremely short neural spines, lack of a sacral series, high
      lumbar variability, and the presence of six instead of seven cervical vertebrae.
      This study documents vertebral morphology, size, and lumbar variation in 71
      skeletons of Trichechus manatus latirostris (Florida manatee) and uses the
      skeletons of Trichechus senegalensis (west African manatee) and Dugong dugon
      (dugong) in comparative analysis. Vertebral traits are used to define
      morphological, and by inference developmental, column modules and to propose
      their hierarchical relationships. A sequence of evolutionary innovations in
      column morphology is proposed. Results suggest that the origin of the fluke and
      low rates of cervical growth originated before separation of trichechids
      (manatees) and dugongids (dugongs). Meristic reduction in count is a later,
      trichechid innovation and is expressed across the entire precaudal column.
      Elongation of thoracic vertebrae may be an innovative strategy to generate an
      elongate column in an animal with a small precaudal count. Elimination of the
      lumbus through both meristic and homeotic reduction is currently in progress.

PMID- 17516430
TI  - Sink or swim? Bone density as a mechanism for buoyancy control in early
      cetaceans.
AB  - Previous analyses have shown that secondarily aquatic tetrapods, including
      whales, exhibit osteological adaptations to life in water as part of their
      complex buoyancy control systems. These structural specializations of bone span
      hyperostosis through osteoporosis. The past 15 years of paleontological effort
      has provided an unprecedented opportunity to examine the osteological
      transformation of whales as they make their transition to an obligate aquatic
      lifestyle over a 10-million-year period. It is hypothesized that whales manifest
      their osteological specialization in the same manner as extant semiaquatic and
      fully aquatic mammals. This study presents and analysis of the microstructural
      features of bone in early and late archaic cetaceans, and in a comparative sample
      of modern terrestrial, semiaquatic, and aquatic mammals. Bone histology was
      examined from the ribs of 10 fossilized individuals representing five early
      cetacean families, including Pakicetidae, Ambulocetidae, Protocetidae,
      Remintonocetidae, and Basilosauridae. Comparisons were then made with rib
      histology from nine genera of extant mammals including: Odocoileus (deer), Bos
      (cow), Equus (horse), Canis (dog), Lutra (river otter), Enhydra (sea otter),
      Choeropsis (pygmy hippo), Trichechus (sea cow), and Delphinus (dolphin). Results
      show that the transition from terrestrial, to semiaquatic, to obligate aquatic
      locomotion in archaeocetes involved a radical shift in bone function achieved by
      means of profound changes at the microstructural level. A surprising finding was
      that microstructural change predates gross anatomical shift in archaeocetes
      associated with swimming. Histological analysis shows that high bone density is
      an aquatic specialization that provides static buoyancy control (ballast) for
      animals living in shallow water, while low bone density is associated with
      dynamic buoyancy control for animals living in deep water. Thus, there was a
      shift from the typical terrestrial form, to osteopetrosis and
      pachyosteosclerosis, and then to osteoporosis in the first quarter of cetacean
      evolutionary history.

PMID- 17516431
TI  - Evolution of hyperphalangy and digit reduction in the cetacean manus.
AB  - Cetaceans (whales, dolphins, and porpoises) have a soft tissue flipper that
      encases most of the forelimb, and elongated digits with an increased number of
      phalanges (hyperphalangy). In addition, some cetaceans exhibit a reduction in
      digit number. Although toothed cetaceans (odontocetes) are pentadactylous, most
      baleen whales (mysticetes) are tetradactylous and also lack a metacarpal. This
      study conducts a survey of cetacean metacarpal and phalangeal morphologies,
      traces the evolution of hyperphalangy in a phylogenetic context, optimizes
      characters onto previously published cetacean phylogenies, and tests various
      digit loss hypotheses. Dissections were performed on 16 cetacean flippers
      representing 10 species (8 mysticetes, 2 odontocetes). Phalangeal count data were
      derived from forelimb radiographs (36 odontocetes, 5 mysticetes), osteological
      specimens of articulated forelimbs (8 mysticetes), and were supplemented with
      published counts. Modal phalangeal counts were coded as ordered and unpolarized
      characters and optimized onto two known cetacean phylogenies. Results indicate
      that digital ray I is reduced in many cetaceans (except Globicephala) and all
      elements of digital ray I were lost in tetradactylous mysticetes. Fossil evidence
      indicates this ray may have been lost approximately 14 Ma. Most odontocetes also
      reduce the number of phalangeal elements in digit V, while mysticetes typically
      retain the plesiomorphic condition of three phalanges. Results from modal
      phalangeal counts show the greatest degree of hyperphalangy in digits II and III
      in odontocetes and digits III and IV in mysticetes. Fossil evidence indicates
      cetacean hyperphalangy evolved by at least 7-8 Ma. Digit loss and digit
      positioning may underlie disparate flipper shapes, with narrow, elongate flippers
      facilitating fast swimming and broad flippers aiding slow turns. Hyperphalangy
      may help distribute leading edge forces, and multiple interphalangeal joints may
      smooth leading edge flipper contour.

PMID- 17516432
TI  - Forelimb myology of the pygmy hippopotamus (Choeropsis liberiensis).
AB  - Based on morphological analyses, hippos have traditionally been classified as
      Suiformes, along with pigs and peccaries. However, molecular data indicate hippos
      and cetaceans are sister taxa (see review in Uhen, 2007, this issue). This study
      analyzes soft tissue characters of the pygmy hippo forelimb to elucidate the
      functional anatomy and evolutionary relationships of hippos within Artiodactyla.
      Two specimens from the National Zoological Park in Washington, D.C. were
      dissected, revealing several adaptations to an aquatic lifestyle. However, these
      adaptations differ functionally from most aquatic mammals as hippos walk along
      river or lake bottoms, rather than swim. Several findings highlight a robust
      mechanism for propelling the trunk forward through the water. For example, mm.
      pectoralis superficialis and profundus demonstrate broad sites of origin, while
      the long flexor tendons serve each of the digits, reflecting the fact that all
      toes are weight-bearing. Pygmy hippos also have eight mm. interossei and a well
      developed m. lumbricalis IV. Retention of intrinsic adductors functions to
      prevent splaying of the toes, an advantageous arrangement in an animal walking on
      muddy substrates. Published descriptions indicate common hippos share all of
      these features. Hippo and ruminant forelimbs share several traits; however,
      hippos are unique among artiodactyls in retaining several primitive muscles
      (e.g., mm. palmaris longus and flexor digitorum brevis). These findings are
      consistent with the hypothesis that hippos diverged from other Artiodactyla early
      in the history of this group. Additional analyses of hindlimb and axial muscles
      may help determine whether this trajectory was closely allied to that of Cetacea.

PMID- 17516433
TI  - Cetacean brains: how aquatic are they?
AB  - The adaptation of cetaceans to a fully aquatic lifestyle represents one of the
      most dramatic transformations in mammalian evolutionary history. Two of the most
      salient features of modern cetaceans are their fully aquatic lifestyle and their
      large brains. This review article will offer an overview of comparative
      neuroanatomical research on aquatic mammals, including analyses of odontocete
      cetacean, sirenian, pinniped, and fossil archaeocete brains. In particular, the
      question of whether a relationship exists between being fully aquatic and having
      a large brain is addressed. It has been hypothesized that the large, well
      developed cetacean brain is a direct product of adaptation to a fully aquatic
      lifestyle. The current consensus is that the paleontological evidence on brain
      size evolution in cetaceans is not consistent with this hypothesis. Cetacean
      brain enlargement took place millions of years after adaptation to a fully
      aquatic existence. Neuroanatomical comparisons with sirenians and pinnipeds
      provide no evidence for the idea that the odontocete's large brain, high
      encephalization level, and extreme neocortical gyrification is an adaptation to a
      fully aquatic lifestyle. Although echolocation has been suggested as a reason for
      the high encephalization level in odontocetes, it should be noted that not all
      aquatic mammals echolocate and echolocating terrestrial mammals (e.g., bats) are
      not particularly highly encephalized. Echolocation is not a requirement of a
      fully aquatic lifestyle and, thus, cannot be considered a sole effect of
      aquaticism on brain enlargement. These results indicate that the high
      encephalization level of odontocetes is likely related to their socially complex
      lifestyle patterns that transcend the influence of an aquatic environment.

PMID- 17516434
TI  - Sound transmission in archaic and modern whales: anatomical adaptations for
      underwater hearing.
AB  - The whale ear, initially designed for hearing in air, became adapted for hearing
      underwater in less than ten million years of evolution. This study describes the
      evolution of underwater hearing in cetaceans, focusing on changes in sound
      transmission mechanisms. Measurements were made on 60 fossils of whole or partial
      skulls, isolated tympanics, middle ear ossicles, and mandibles from all six
      archaeocete families. Fossil data were compared with data on two families of
      modern mysticete whales and nine families of modern odontocete cetaceans, as well
      as five families of noncetacean mammals. Results show that the outer ear pinna
      and external auditory meatus were functionally replaced by the mandible and the
      mandibular fat pad, which posteriorly contacts the tympanic plate, the lateral
      wall of the bulla. Changes in the ear include thickening of the tympanic bulla
      medially, isolation of the tympanoperiotic complex by means of air sinuses,
      functional replacement of the tympanic membrane by a bony plate, and changes in
      ossicle shapes and orientation. Pakicetids, the earliest archaeocetes, had a land
      mammal ear for hearing in air, and used bone conduction underwater, aided by the
      heavy tympanic bulla. Remingtonocetids and protocetids were the first to display
      a genuine underwater ear where sound reached the inner ear through the mandibular
      fat pad, the tympanic plate, and the middle ear ossicles. Basilosaurids and
      dorudontids showed further aquatic adaptations of the ossicular chain and the
      acoustic isolation of the ear complex from the skull. The land mammal ear and the
      generalized modern whale ear are evolutionarily stable configurations, two ends
      of a process where the cetacean mandible might have been a keystone character.

PMID- 17516435
TI  - Anatomical predictions of hearing in the North Atlantic right whale.
AB  - Some knowledge of the hearing abilities of right whales is important for
      understanding their acoustic communication system and possible impacts of
      anthropogenic noise. Traditional behavioral or physiological techniques to test
      hearing are not feasible with right whales. Previous research on the hearing of
      marine mammals has shown that functional models are reliable estimators of
      hearing sensitivity in marine species. Fundamental to these models is a
      comprehensive analysis of inner ear anatomy. Morphometric analyses of 18 inner
      ears from 13 stranded North Atlantic right whales (Eubalaena glacialis) were used
      for development of a preliminary model of the frequency range of hearing.
      Computerized tomography was used to create two-dimensional (2D) and 3D images of
      the cochlea. Four ears were decalcified and sectioned for histologic measurements
      of the basilar membrane. Basilar membrane length averaged 55.7 mm (range, 50.5 mm
      61.7 mm). The ganglion cell density/mm averaged 1,842 ganglion cells/mm. The
      thickness/width measurements of the basilar membrane from slides resulted in an
      estimated hearing range of 10 Hz-22 kHz based on established marine mammal
      models. Additional measurements from more specimens will be necessary to develop
      a more robust model of the right whale hearing range.

PMID- 17516436
TI  - Complaining about quality assurance in gynecologic cytology: a window that is now
      closing.

PMID- 17516437
TI  - Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell
      lung cancer (NSCLC).
AB  - BACKGROUND: The clinical results after stereotactic single-dose radiotherapy of
      nonsmall-cell lung cancer (NSCLC) stages I and II were evaluated. METHODS: Forty
      two patients with biopsy-proven NSCLC received stereotactic radiotherapy.
      Patients were treated in a stereotactic body frame and breathing motion was
      reduced by abdominal compression. The single doses used ranged between 19 and 30
      Gy/isocenter. RESULTS: After a median follow-up period of 15 months (range, 1.5
      72 months) the actuarial overall survival rates and disease-free survival rates
      were 74.5%, 65.4%, 37.4%, and 70.2%, 49.1%, 49.1% at 12, 24, and 36 months after
      therapy, respectively. The actuarial local tumor control rates were 89.5%, 67.9%,
      and 67.9% at 12, 24, and 36 months after therapy, respectively. A significant
      difference (P = .032) in local tumor control was found for patients receiving 26
      30 Gy (n = 32) compared with doses of less than 26 Gy (n = 10). The effect of the
      tumor volume on local tumor control was also evaluated. Although the difference
      was not statistically significant (P = .078), the subgroup of tumors with a tumor
      volume of less than 12 cm(3) (n = 10) experienced no tumor recurrence. Thirteen
      (31%) patients developed metastases during follow-up, whereas isolated regional
      lymph node recurrence was only encountered in 2 patients. No clinically
      significant treatment-associated side effects were documented. CONCLUSIONS:
      Stereotactic single-dose radiotherapy is a safe and effective treatment option
      for patients with early stage NSCLC not suitable for surgery. Especially for
      small tumor volumes it seems to be equally effective as hypofractionated
      radiotherapy, while minimizing the overall treatment time.

PMID- 17516438
TI  - Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy
      in acute lymphoblastic leukemia patients.
AB  - BACKGROUND: Rapid clearance of poly(ethylene glycol)-asparaginase (PEG-ASNase)
      has been reported for up to one-third of patients treated for acute lymphoblastic
      leukemia (ALL), potentially rendering their treatment ineffective. A 25%
      occurrence of an antibody against PEG (anti-PEG) was previously reported in
      healthy blood donors. The objective of the study was to determine whether anti
      PEG was associated with rapid clearance PEG-ASNase. METHODS: The investigation
      reanalyzed stored sera from pediatric patients enrolled in the ALL Berlin
      Frankfurt-Muenster 2000 studies. Twenty-eight samples were selected to include 15
      subjects with undetectable ASNase activity after receiving PEG-ASNase. Sixteen
      subjects treated with unmodified ASNase were also included, 8 with low ASNase
      activity. Sera were tested for anti-PEG using 2 techniques: 1) serology, by
      agglutination of PEG-coated red blood cells; 2) flow cytometry, by analysis of 10
      microm PEG beads stained for bound immunoglobulins. RESULTS. Of the 15 sera from
      PEG-ASNase-treated patients with undetectable ASNase activity, anti-PEG was
      detected in 9 by serology and in 12 by flow cytometry. Anti-PEG was detected in 1
      PEG-ASNase-treated patient with lower ASNase activity (123 U/L). No relation was
      observed between anti-PEG and serum ASNase activity for patients treated with
      unmodified ASNase. CONCLUSIONS: The presence of anti-PEG was very closely
      associated with rapid clearance of PEG-ASNase. Further comprehensive studies are
      warranted to fully elucidate the effect of anti-PEG on PEG-conjugated agents.
      Screening and monitoring for anti-PEG may allow identification of patients for
      whom a modified dosing strategy or use of a non-PEGylated drug would be
      appropriate.

PMID- 17516439
TI  - Thar she blows... and dives, and feeds, and talks, and hears, and thinks: the
      anatomical adaptations of aquatic mammals.

PMID- 17516440
TI  - Anatomical adaptations of aquatic mammals.
AB  - This special issue of the Anatomical Record explores many of the anatomical
      adaptations exhibited by aquatic mammals that enable life in the water.
      Anatomical observations on a range of fossil and living marine and freshwater
      mammals are presented, including sirenians (manatees and dugongs), cetaceans
      (both baleen whales and toothed whales, including dolphins and porpoises),
      pinnipeds (seals, sea lions, and walruses), the sea otter, and the pygmy
      hippopotamus. A range of anatomical systems are covered in this issue, including
      the external form (integument, tail shape), nervous system (eye, ear, brain),
      musculoskeletal systems (cranium, mandible, hyoid, vertebral column,
      flipper/forelimb), digestive tract (teeth/tusks/baleen, tongue, stomach), and
      respiratory tract (larynx). Emphasis is placed on exploring anatomical function
      in the context of aquatic life. The following topics are addressed: evolution,
      sound production, sound reception, feeding, locomotion, buoyancy control,
      thermoregulation, cognition, and behavior. A variety of approaches and techniques
      are used to examine and characterize these adaptations, ranging from dissection,
      to histology, to electron microscopy, to two-dimensional (2D) and 3D computerized
      tomography, to experimental field tests of function. The articles in this issue
      are a blend of literature review and new, hypothesis-driven anatomical research,
      which highlight the special nature of anatomical form and function in aquatic
      mammals that enables their exquisite adaptation for life in such a challenging
      environment.

PMID- 17516441
TI  - Evolution of marine mammals: back to the sea after 300 million years.
AB  - The fossil record demonstrates that mammals re-entered the marine realm on at
      least seven separate occasions. Five of these clades are still extant, whereas
      two are extinct. This review presents a brief introduction to the phylogeny of
      each group of marine mammals, based on the latest studies using both
      morphological and molecular data. Evolutionary highlights are presented, focusing
      on changes affecting the sensory systems, locomotion, breathing, feeding, and
      reproduction in Cetacea, Sirenia, Desmostylia, and Pinnipedia. Aquatic
      adaptations are specifically cited, supported by data from morphological and
      geochemical studies. For example, analysis of oxygen isotopes incorporated into
      fossil tooth enamel indicates whether these mammals foraged in (and, therefore,
      ingested) fresh water or sea water. Comparisons between groups are made to see if
      there are any common patterns, particularly relating to adaptations to aquatic
      life. Results show that aquatic characteristics evolved in mosaic patterns and
      that different morphological solutions to aquatic conditions were achieved
      separately in each of these groups. Changes in the axial and appendicular
      skeleton assist with locomotion for aquatic foraging. Nostril and eye placement
      modifications accommodate wading versus underwater foraging needs. All groups
      exhibit aquatic adaptations directly related to feeding, particularly changes in
      the dentition and rostrum. The earliest representatives of these clades all show
      morphological features that indicate they were feeding while in the water,
      suggesting that feeding ecology is a key factor in the evolution of marine
      mammals.

PMID- 17516442
TI  - Use of tusks in feeding by dugongid sirenians: observations and tests of
      hypotheses.
AB  - Most living and fossil sea cows of the subfamily Dugonginae (Dugongidae, Sirenia,
      Mammalia) are characterized by large upper incisor tusks, which are thought to
      play an important role (at least primitively) in feeding on seagrass rhizomes.
      Testing this hypothesis is difficult, because the only extant tusked sirenian
      (Dugong dugon) is morphologically and perhaps behaviorally aberrant. The tests
      attempted here involve examination of stomach contents of wild Recent dugongs,
      experiments using plastic replicas of diverse tusks to harvest seagrasses, gross
      anatomical observations on tusks and skulls, measurements of tusk tip geometry,
      and observations of microwear on tusks. We conclude that (a) male D. dugon (with
      erupted tusks) do not consume more rhizomes than females (without erupted tusks);
      (b) the tusks do not play a significant role in feeding in the modern dugong; (c)
      larger, more bladelike tusks are more effective at harvesting rhizomes, but the
      effect of shape was not experimentally separated from the effect of exposed tusk
      length; (d) some fossil dugongines show apparent cranial adaptations for downward
      and backward cutting motions of their large, bladelike tusks; (e) geometry of
      wear surfaces is consistent with use of at least the more bladelike tusks as
      cutting instruments; (f) preliminary observations of microwear in D. dugon do not
      indicate more than occasional use of the tusks in purposeful harvesting of
      rhizomes, and then only opportunistically by large adult males. The hypothesis of
      such tusk use by extinct dugongines (in contrast to the living species) is so far
      corroborated, but available data and tests do not suffice to establish this
      conclusively.

PMID- 17516443
TI  - Breaking symmetry: the marine environment, prey size, and the evolution of
      asymmetry in cetacean skulls.
AB  - Skulls of odontocetes (toothed whales, including dolphins and porpoises) are
      typified by directional asymmetry, particularly in elements associated with the
      airway. Generally, it is assumed this asymmetry is related to biosonar
      production. However, skull asymmetry may actually be a by-product of selection
      pressure for an asymmetrically positioned larynx. The odontocete larynx traverses
      the pharynx and is held permanently in place by a ring of muscle. This allows
      prey swallowing while remaining underwater without risking water entering the
      lungs and causing injury or death. However, protrusion of the larynx through the
      pharynx causes a restriction around which prey must pass to reach the stomach.
      The larynx and associated hyoid apparatus has, therefore, been shifted to the
      left to provide a larger right piriform sinus (lateral pharyngeal food channel)
      for swallowing larger prey items. This asymmetry is reflected in the skull,
      particularly the dorsal openings of the nares. It is hypothesized that there is a
      relationship between prey size and skull asymmetry. This relationship was
      examined in 13 species of odontocete cetaceans from the northeast Atlantic,
      including four narrow-gaped genera (Mesoplodon, Ziphius, Hyperoodon, and Kogia)
      and eight wide-gaped genera (Phocoena, Delphinus, Stenella, Lagenorhynchus,
      Tursiops, Grampus, Globicephala, and Orcinus). Skulls were examined from 183
      specimens to assess asymmetry of the anterior choanae. Stomach contents were
      examined from 294 specimens to assess prey size. Results show there is a
      significant positive relationship between maximum relative prey size consumed and
      average asymmetry relative to skull size in odontocete species (wide-gape
      species: R2 = 0.642, P = 0.006; narrow-gape species: R2 = 0.909, P = 0.031). This
      finding provides support for the hypothesis that the directional asymmetry found
      in odontocete skulls is related to an aquatic adaptation enabling swallowing
      large, whole prey while maintaining respiratory tract protection.

PMID- 17516444
TI  - Adaptations of the cetacean hyolingual apparatus for aquatic feeding and
      thermoregulation.
AB  - Foraging methods vary considerably among semiaquatic and fully aquatic mammals.
      Semiaquatic animals often find food in water yet consume it on land, but as truly
      obligate aquatic mammals, cetaceans (whales, dolphins, and porpoises) must
      acquire and ingest food underwater. It is hypothesized that differences in
      foraging methods are reflected in cetacean hyolingual apparatus anatomy. This
      study compares the musculoskeletal anatomy of the hyolingual apparatus in 91
      cetacean specimens, including 8 mysticetes (baleen whales) in two species and 91
      odontocetes (toothed whales) in 11 species. Results reveal specific adaptations
      for aquatic life. Intrinsic fibers are sparser and extrinsic musculature
      comprises a significantly greater proportion of the cetacean tongue relative to
      terrestrial mammals and other aquatic mammals such as pinnipeds and sirenians.
      Relative sizes and connections of cetacean tongue muscles to the hyoid apparatus
      relate to differences in feeding methods used by cetaceans, specifically
      filtering, suction, and raptorial prehension. In odontocetes and eschrichtiids
      (gray whales), increased tongue musculature and enlarged hyoids allow grasping
      and/or lingual depression to generate intraoral suction for prey ingestion. In
      balaenopterids (rorqual whales), loose and flaccid tongues enable great
      distention of the oral cavity for prey engulfing. In balaenids (right and bowhead
      whales), large but stiffer tongues direct intraoral water flow for continuous
      filtration feeding. Balaenid and eschrichtiid (and possibly balaenopterid)
      mysticete tongues possess vascular retial adaptations for thermoregulation and
      large amounts of submucosal adipose tissue for nutritional storage. All cetacean
      tongues also function in prey transport and swallowing. These hyolingual
      musculoskeletal differences are unique cetacean anatomical adaptations for
      foraging entirely in an aquatic environment.

PMID- 17516445
TI  - Blowing bubbles: an aquatic adaptation that risks protection of the respiratory
      tract in humpback whales (Megaptera novaeangliae).
AB  - Cetaceans (whales, dolphins, and porpoises) have developed extensive protective
      barriers to exclude water or food from the respiratory tract, including valvular
      nostrils, an intranarial elongated larynx, and a sphincteric soft palate. A
      barrier breach can be lethal, as asphyxiation may occur from incursions of water
      (drowning) or food (choking). Humpback whales (Megaptera novaeangliae), however,
      exhibit a possibly unique and paradoxical behavior concerning respiratory
      protection: they release a "bubble cloud" (a cluster of tiny bubbles) underwater
      from the mouth. How they do this remains unclear. This study tests the hypothesis
      that the larynx plays a role in enabling bubble cloud emission. The anatomy and
      position of the larynx was examined in seven specimens of Megaptera novaeangliae.
      Results indicate that the epiglottis can be manually removed from behind the soft
      palate and placed in the oral cavity during dissection. Unlike that of toothed
      whales (odontocetes), the humpback whale larynx does not appear to be permanently
      intranarial. The elongated and trough-shaped epiglottis may function as a tube
      when placed against the undersurface of the soft palate and, thus, facilitate
      channeling air from the larynx to the oral cavity. The pointed tip and lateral
      edges of the epiglottis fit tightly against the undersurface of the soft palate,
      perhaps functioning as a one-way valve that lets air out but prevents water from
      entering. Bubble cloud generation likely involves air passing directly from the
      larynx into the oral cavity, and then expulsion through the mesh of the baleen
      plates. A laryngeal-oral connection, however, compromises the anatomical aquatic
      adaptations that normally protect the respiratory tract. A potential for drowning
      exists during the critical interval in which the larynx is intraoral and during
      re-insertion back to the normal intranarial position. The retention of this risky
      behavior indicates the importance of bubble clouds in predator avoidance, prey
      capture, and/or social signaling.

PMID- 17516446
TI  - Initial treatment patterns and outcome of contemporary prostate cancer patients
      with bone metastases at initial presentation: data from CaPSURE.
AB  - BACKGROUND: The current study utilized the CaPSURE disease registry to describe
      the natural history, initial treatment, and factors correlated with mortality in
      patients who were diagnosed with bony metastatic disease (M+) at the time of
      initial presentation. METHODS: Treatment patterns at the time of diagnosis were
      analyzed. Two Cox proportional hazards models were developed, with outcomes of
      all cause-specific mortality and prostate cancer-specific mortality in patients
      with M+ disease. Clinical and sociodemographic variables were included in a
      backward stepwise procedure to identify predictors of mortality. RESULTS: Of
      12,005 patients diagnosed between 1990-2004, 284 (2.4%) were diagnosed with M+
      disease. After a median follow-up period of 3.8 years, 107 patients (39%) died.
      Of those who died, 68 (64%) died of causes related to prostate cancer, whereas 39
      (36%) had died of causes not related to prostate cancer. The 5-year survival of
      all patients was 71% and the median survival had not been reached at the time of
      last follow-up. Approximately 84% of patients received some form of hormonal
      therapy within 6 months of diagnosis, the use of which increased throughout the
      study period. Prostate cancer-specific mortality was found to be correlated with
      the presence of comorbid illness, younger age at diagnosis, and a Gleason score
      >7 in the primary tumor. CONCLUSIONS: Patients with M+ prostate cancer have a
      protracted natural history and a median survival that exceeds 5 years. Hormonal
      therapy is the mainstay for such patients. Comorbid illness, young age at
      diagnosis, and cancer grade appear to negatively affect the disease-specific
      survival.

PMID- 17516447
TI  - Discovery of a low frequency sound source in Mysticeti (baleen whales):
      anatomical establishment of a vocal fold homolog.
AB  - The mechanism of mysticete (baleen whale) vocalization has remained a mystery.
      Vocal folds (true vocal "cords"), the structures responsible for sound production
      in terrestrial mammals, were thought to be absent in whales. This study tests the
      hypothesis that the mysticete larynx possesses structures homologous to vocal
      folds and that they are capable of sound generation. Laryngeal anatomy was
      examined in 37 specimens representing 6 mysticete species. Results indicate the
      presence of a U-shaped fold (U-fold) in the lumen of the larynx. The U-fold is
      supported by arytenoid cartilages, controlled by skeletal muscles innervated by
      the recurrent laryngeal nerve, is adjacent to a diverticulum (laryngeal sac)
      covered with mucosa innervated by the superior laryngeal nerve, and contains a
      ligament-conditions that also define the vocal folds of terrestrial mammals and,
      therefore, supports homology. Unlike the vocal folds of terrestrial mammals,
      which are perpendicular to airflow, the mysticete U-fold is oriented parallel to
      airflow. U-fold adduction/abduction and elevation/depression may control airflow,
      and vibration of its edges may generate sounds. The walls of the laryngeal sac
      can expand and contract, may serve as a resonant space, and may also propagate
      vibrations generated by movements of the supporting arytenoid cartilages. The
      extensive musculature surrounding the laryngeal sac may enable rapid and forceful
      expulsion of air from the lumen of the sac into other respiratory spaces, or
      maintain a constant sac volume despite the effects of ambient pressure (e.g.,
      changes during diving or ascent). The size and complexity of the mysticete larynx
      indicates an organ with multiple functions, including protection during
      breathing/swallowing, regulation of airflow and pressures in the respiratory
      spaces, and sound generation. The presence of a vocal fold homolog offers a new
      insight into both the mechanism of sound generation by mysticetes and the
      divergent evolution of odontocete and mysticete cetaceans.

PMID- 17516448
TI  - Effects of keratinocyte growth factor on intra-alveolar surfactant fixed in situ:
      Quantitative ultrastructural and immunoelectron microscopic analysis.
AB  - Quantitative (immuno) transmission electron microscopy using design-based
      stereology was performed on specimens collected by means of systematic uniform
      random sampling of rat lungs, which were fixed by vascular perfusion to stabilize
      intra-alveolar surfactant in situ. This procedure ensures that the data recorded
      are representative of the whole organ. Ultrathin sections of specimens embedded
      at low temperature in Lowicryl HM20 were labeled by indirect immuno-gold staining
      for surfactant protein A. We observed that, 3 days after treatment of lungs in
      vivo with truncated keratinocyte growth factor (DeltaN23-KGF), a potent mitogen
      of alveolar epithelial type II cells, surfactant protein A associated with the
      tubular myelin fraction of intra-alveolar surfactant was increased by 47% in
      comparison with buffer-treated control lungs. Despite the marked type II cell
      hyperplasia, the relative amount of ultrastructural surfactant subtypes was not
      significantly affected. Because surfactant protein A reduces the sensitivity to
      inhibition of the biophysical activity of surfactant by exudating plasma
      proteins, we propose that pretreatment of lungs with DeltaN23-KGF ameliorates
      adverse effects observed in acute lung injury following, for example, ischemia
      and reperfusion.

PMID- 17516449
TI  - Contribution to the knowledge of anatomy of species of genus Mobula Rafinesque
      1810 (Chondricthyes: Mobulinae).
AB  - A comparative anatomical study was conducted among four mobulid species (Mobula
      japanica, M. munkiana, M. tarapacana, and M. thurstoni), from the coasts of the
      Gulf of California. Characters of the skeleton (neurocranium, mandibles, scapular
      girdle, pelvic girdle, and synarcual) were described. Mobula species had a wide
      structural variation. In the skeleton, M. tarapacana displayed the most
      plesiomorphic characters, mainly at the cranial level (cranium longer than wide,
      reduced internasal width, fontanelle longer than wide), while M. japanica had the
      most derived characters (cranium wider than longer, fontanelle wider than
      longer). Based on the observations, the dorsal cephalic musculature were similar
      in all species; however, oppositely to other batoid species, the epiaxilis is
      strongly developed, as it extends toward the cephalic part of the neurocranium,
      at level of the postorbital processes. In the ventral musculature, ventral
      constrictor muscles are quite reduced, whereas complex mandibular muscles are
      very developed. Muscles showing the highest variation are the coracohioideus and
      the coracoarcual.

PMID- 17516450
TI  - Short-term cortical plasticity in patients with dystonia: a study with repetitive
      transcranial magnetic stimulation.
AB  - Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency
      and suprathreshold (RMT) intensity produces a progressive facilitation of motor
      evoked potential (MEP) amplitude that outlasts the end of stimulation. This
      phenomenon is related to a short-term enhancement of cortical excitatory
      interneurones. In this study, we investigated whether 5 Hz-rTMS elicits similar
      MEP facilitation during stimulation and similar facilitatory after-effects in
      patients with upper limb dystonia and healthy subjects. Trains of 5, 10, and 20
      stimuli were delivered at 120% RMT over the primary motor cortex with the
      subjects at rest. rTMS-trains were followed by single test stimuli delivered at
      various interstimulus intervals (0.5-10 s) at 120% RMT using a conditioning-test
      paradigm. Single conditioning stimuli were also delivered. The effects of
      suprathreshold 1 Hz-rTMS were also tested. The MEP amplitude during the course of
      the trains and of the test stimuli was measured. In control experiments, we
      investigated the role of the afferent inputs elicited by muscle twitches after
      ulnar nerve stimulation on the MEP amplitude. In patients and healthy subjects,
      MEP amplitude increased significantly during the course of 5 Hz-trains. In both
      groups the MEP facilitation outlasted the end of 5 Hz-rTMS, however the
      facilitatory after-effects were more pronounced and lasted longer in patients
      than in healthy subjects. MEP amplitudes during and after 1 Hz-rTMS remained
      unchanged. Ulnar nerve stimulation did not change the test MEP amplitude. We
      conclude that in patients with upper limb dystonia there is an abnormal recovery
      from MEP facilitation after suprathreshold 5 Hz-rTMS suggesting an abnormal
      pattern of short-term cortical plasticity.

PMID- 17516451
TI  - A morphological and 13C NMR study of the extramandibular fat bodies of the
      striped dolphin (Stenella coeruleoalba).
AB  - The molecular and histological structure of the fat bodies covering externally
      the posterolateral region of the jaw of the striped dolphin (Stenella
      coeruleoalba) was investigated by means of morphological and nuclear magnetic
      resonance techniques. The analyses of samples belonging to adult and juvenile
      individuals were performed with the aim of seeking the presence of age-related
      differences. In our study, the level of isovalerate (iso5:0) in the
      extramandibular fat of the juvenile individuals is comparable with those of the
      adult counterparts; conversely, longer isobranched fatty acids were detected in
      lower quantities in the juveniles together with a higher degree of unsaturation.
      The morphologic analyses revealed that, in both adults and juveniles, this fatty
      tissue is similar to univacuolar adipose tissue. However, in the juveniles, a
      muscular component was present, whereas only in adult subjects, enlarged and
      irregularly shaped cavities may be seen within the adipose tissue. These
      cavities, structurally organized as veins, may regulate blood flow in response to
      changing water temperature and stabilize thermal gradient within the jaw lipids.
      These data suggest that the molecular components and the histological
      organization can indicate a maturation of the organ with age that probably may
      reflect different sound reception properties.

PMID- 17516452
TI  - Paul Blocq and (psychogenic) astasia abasia.
AB  - The Greek term astasia-abasia literally translates to mean inability to stand and
      to walk. Although today we would classify the syndrome as a conversion disorder,
      it was considered a separate disease by Paul Blocq (1860-1896), who described
      this phenomenon as the inability to maintain an upright posture, despite normal
      function of the legs in the bed. Paul Blocq's original 1888 articles on astasia
      abasia were read, partly translated from French to English, and the cases were
      summarized. A review of a selection of the literature following Blocq's
      description on astasia abasia was performed. Present day literature was consulted
      as well. Blocq reviewed what was known about astasia abasia in two papers.
      Although he was the first to use the combined term astasia abasia, he referred to
      similar descriptions of Charcot, Richer, Mitchell, Jaccoud, Romei, and
      Erlenmeyer. Blocq's contribution was in compiling the experiences and
      observations of preeminent 19th century neurologists. He recognized that
      paralysis, jumping, fits, tremor, and bizarre behavior could all be associated
      with the syndrome. He distinguished the disorder from hysteria. Moreover, he
      presented a formal delineation of the gait disorder and provided a
      pathophysiologic concept. Prognosis was considered favorable. Paul Blocq directed
      attention to psychogenic gait disorders by publishing a small case series on
      astasia abasia. Today, these case descriptions would be likely considered cases
      of conversion or psychogenic gait disorder, with or without other
      conversion/psychogenic movement disorders.

PMID- 17516453
TI  - Prospective neuroimaging study in hereditary spastic paraplegia with thin corpus
      callosum.
AB  - Our objective was to estimate the frequency as well as to establish the clinical
      and neuroimaging profile of hereditary spastic paraplegia with thin corpus
      callosum (HSP-TCC). HSP-TCC was recognized as a specific clinical subtype of HSP
      and mapped to chromosome (ch) 15q13-15 in Japanese families. It has been
      considered rare in western countries. We assessed 45 patients with autosomal
      recessive HSP from 20 different families in search of clinical and imaging
      criteria for the diagnosis of HSP-TCC. In addition, HSP-TCC patients underwent
      further neurological, imaging and genetic evaluation. MRI scans were performed in
      a 2T scanner and sagittal T1 weighted images used for semiautomated volumetric
      measurements of corpus callosum, cerebellum, and brain. In seven patients, a 2
      year follow-up MRI scan was performed. We genotyped seven microsatellite markers
      flanking the 15q13-15 candidate region and calculated two-point and multipoint
      LOD scores (Z). We identified 13 patients from seven unrelated families with HSP
      TCC. MRI showed significant corpus callosum, cerebral and cerebellar volumetric
      reductions (P<0.001, P=0.03, and P=0.01, respectively). In the prospective
      analysis, we found progressive corpus callosum atrophy (P=0.04). Two-point and
      multipoint LOD scores were significantly negative for markers genotyped on ch
      15q. However, independent pedigree analysis did not yield significant results.
      HSP-TCC was found in 35% of families with autosomal recessive HSP. MRI volumetry
      showed cerebral and cerebellar atrophy in association with progressive corpus
      callosum thinning. Genetic studies did not show evidence for linkage to ch 15q.

PMID- 17516454
TI  - Inhibitory control and spatial working memory in Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) have difficulty performing tasks relying
      on inhibitory control and working memory, functions of the prefrontal cortex. Eye
      movement paradigms can be used to investigate basic sensorimotor functions and
      higher order cognitive aspects of motor control. This study investigated
      inhibitory control and spatial working memory in the saccadic system of 13
      individuals with mild-moderate PD and 13 age-matched controls. Tasks explored
      suppression of reflexive saccades during qualitatively different tasks,
      generation of express and anticipatory saccades, and the ability to respond to
      occasional, unpredictable ("oddball") targets that occurred during a sequence of
      well-learned, reciprocating saccades between horizontal targets. Spatial working
      memory was assessed using single and two-step (involving a visually guided
      saccade during the delay period) memory-guided tasks. Results for the PD group
      indicated an increased percentage of response selection errors during an oddball
      task, reduced suppression of inappropriate reflexive saccades during memory
      guided tasks (but not during fixation or saccade-engagement tasks), and an
      increased percentage of express and anticipatory saccades. Spatial working memory
      was preserved in the PD group during single and two-step memory-guided tasks.
      These findings are consistent with dysfunction within fronto-striatal and
      prefrontal-collicular pathways influencing suppression and selection of eye
      movements.

PMID- 17516455
TI  - State of the art in restless legs syndrome therapy: practice recommendations for
      treating restless legs syndrome.
AB  - Dopaminergic agents are the best-studied agents and are considered first-line
      treatment of restless legs syndrome (RLS). Extensive data are available for
      levodopa, pramipexole, and ropinirole, which have approval for the indication
      RLS, and to a smaller extent for cabergoline, pergolide, and rotigotine. Apart
      from one recent study, comparing two active drugs (levodopa and cabergoline), no
      comparative studies have been published. The individual treatment regimen with
      the most appropriate agent concerning efficacy and side effects has to be
      selected by the treating physician. On the basis of these clinical trials and
      expert opinion of the authors, a treatment algorithm is proposed to support the
      search for the optimal individual treatment. Opioids and anticonvulsants such as
      gabapentine are second-line options in individual patients. Iron substitution is
      justified in people with iron deficiency related RLS (ferritin concentration
      lower than 50 microg/L).

PMID- 17516456
TI  - Alien limb following posterior cerebral artery stroke: failure to recognize
      internally generated movements?
AB  - We describe two rare cases of alien limb syndrome following right posterior
      cerebral artery (PCA) stroke. Both patients present with left hemianopia, visual
      neglect and proprioceptive loss in addition to their alien limb symptoms. Lesion
      subtraction from seven control PCA patients revealed that medial parietal
      occipital and thalamic areas were selectively damaged in the alien limb patients.
      We propose that loss of the sense of motor intention and internal model of the
      current state of the arm, combined with deficient proprioceptive and visual
      feedback of the moving limb, are critical for genesis of posterior alien limb and
      discuss how affected regions normally function to ensure awareness of self
      generated motor activity.

PMID- 17516457
TI  - Does ageing influence deep brain stimulation outcomes in Parkinson's disease?
AB  - We sought to define the influence of ageing in clinical, cognitive, and quality
      of-life outcomes after subthalamic nucleus deep brain stimulation (STN-DBS) in
      Parkinson's disease (PD). We performed motor assessment (UPDRS), mood tests,
      cognitive, and quality of life evaluation (PDQ-39) on PD patients before surgery,
      and 12 and 24 months after, and we recorded adverse events. The variations of
      these parameters after surgery were correlated with age using regression
      statistical tests. Cerebral bleeding risk was evaluated by a nonparametric test.
      We enrolled 45 patients (mean age 60 +/- 9 years, range 40-73). No significant
      correlation was found between age and motor scores and PDQ-39 improvements at 12
      months. At 24 months, there was a significant negative correlation between age
      and the improvement of three dimensions of PDQ 39 (mobility, activities of daily
      life, and cognition). Cognitive impairment showed no correlation, but apathy and
      depression were positively correlated with age. Significant statistical
      difference was observed between cerebral bleeding and age. STN-DBS is an
      effective treatment for elderly patients with advanced PD. A longer follow-up
      duration and a larger population seem necessary to better assess the quality of
      life perception in elderly patients and to determinate the real risk of
      hemorrage.

PMID- 17516458
TI  - A new phenotype of chorea-acanthocytosis with dilated cardiomyopathy and
      myopathy.

PMID- 17516459
TI  - Blockade of HERG K+ channel by an antihistamine drug brompheniramine requires the
      channel binding within the S6 residue Y652 and F656.
AB  - A number of clinically used drugs block delayed rectifier K+ channels and prolong
      the duration of cardiac action potentials associated with long QT syndrome. This
      study investigated the molecular mechanisms of voltage-dependent inhibition of
      human ether-a-go-go-related gene (HERG) delayed rectifier K+ channels expressed
      in HEK-293 cells by brompheniramine, an antihistamine. Brompheniramine inhibited
      HERG current in a concentration-dependent manner with the half-maximal inhibitory
      concentration (IC50) value of 1.7 microm at 0 mV. A block of HERG current by
      brompheniramine was enhanced by progressive membrane depolarization and showed
      significantly negative shift in voltage-dependence of channel activation.
      Inhibition of HERG current by brompheniramine showed time-dependence. The S6
      residue HERG mutant Y652A and F656C largely reduced the blocking potency of HERG
      current. These results indicate that brompheniramine mainly inhibited the HERG
      potassium channel through the residue Y652 and F656 and these residues may be an
      obligatory determinant in inhibition of HERG current for brompheniramine.

PMID- 17516460
TI  - Changes of melanosome morphology associated with the differentiation of epidermal
      melanocytes in slaty mice.
AB  - The slaty (Dct(slt)) mutation is known to reduce the activity of dopachrome
      tautomerase, which converts dopachrome to 5,6-dihydroxyindole-2-carboxylic acid
      in the pathway of eumelanin synthesis and to inhibit melanosome maturation in
      melanocytes. However, it is not known whether the inhibition of melanosome
      maturation in slaty melanocytes is developmentally regulated. To address this
      point, changes in the morphology and maturation of melanosomes in cultured
      epidermal melanocytes derived from newborn mice of wild-type (black) and slaty
      mutant were surveyed under the electron microscope. In black melanocytes
      (Dct(+)), almost all melanosomes were elliptical stage IV melanosomes. However,
      in slaty melanocytes, numerous spherical stage III melanosomes with globular
      depositions of pigment in addition to elliptical stage III melanosomes with
      intraluminal fibrils were observed. Mixed-type melanosomes containing both
      globular deposition and intraluminal fibrils of pigment were also observed. In
      slaty melanocytes, spherical and mixed-type melanosomes were gradually decreased
      after birth, whereas elliptical melanosomes were gradually increased. Stage IV
      melanosomes were very few in slaty melanocytes, and the number did not increase
      after birth. These results suggest that the slaty mutation blocks the melanosome
      maturation at stage III and affects the melanosome morphology (elliptical or
      spherical) in a developmental stage-specific manner.

PMID- 17516461
TI  - An in vivo look at vertebrate liver architecture: three-dimensional
      reconstructions from medaka (Oryzias latipes).
AB  - Understanding three-dimensional (3D) hepatobiliary architecture is fundamental to
      elucidating structure/function relationships relevant to hepatobiliary
      metabolism, transport, and toxicity. To date, factual information on vertebrate
      liver architecture in 3 dimensions has remained limited. Applying noninvasive in
      vivo imaging to a living small fish animal model we elucidated, and present here,
      the 3D architecture of this lower vertebrate liver. Our investigations show that
      hepatobiliary architecture in medaka is based on a polyhedral (hexagonal)
      structural motif, that the intrahepatic biliary system is an interconnected
      network of canaliculi and bile-preductules, and that parenchymal architecture in
      this lower vertebrate is more related to that of the mammalian liver than
      previously believed. The in vivo findings presented advance our comparative 3D
      understanding of vertebrate liver structure/function, help clarify previous
      discrepancies among vertebrate liver conceptual models, and pose interesting
      questions regarding the "functional unit" of the vertebrate liver.

PMID- 17516462
TI  - Relationship between the cytologic reporting rate for high-grade squamous
      intraepithelial lesion or worse and Papanicolaou smear sensitivity: a simple
      mathematic proof with practical implications.

PMID- 17516463
TI  - Peptidomic analysis of human acquired enamel pellicle.
AB  - Human acquired enamel pellicle is the result of a selective interaction of
      salivary proteins and peptides with the tooth surface. In the present work, the
      characterization of the peptides as well as the type of interactions established
      with the enamel surface was performed. Peptides from in vivo bovine enamel
      implants in the human oral cavity were sequentially extracted using guanidine and
      trifluoroacetic acid solutions and the fractions obtained were analysed by LC-MS
      and LC-MS/MS. Based on the LC-MS data, six phosphorylated peptides were
      identified in an intact form, strongly adsorbed to the enamel surface. Data from
      the LC-MS/MS analyses allowed us to identified 30 fragment peptides non
      covalently bonded to enamel [basic proline-rich proteins, histatins (1 and 3) and
      acidic proline-rich protein classes]. The tandem mass spectrometry experiments
      showed the existence of a pattern of amide bond cleavage for the different
      identified peptide classes suggesting a selective proteolytic activity. For
      histatins, a predominance of cleavage at Arg, Lys and His residues was observed,
      while for basic proline-rich proteins, cleavage at Arg and Pro residues
      prevailed. In the case of acidic proline-rich proteins, a clearly predominance of
      cleavage of the Gln-Gly amide bond was evident.

PMID- 17516464
TI  - Existence of low-molecular-weight thiols in Caenorhabditis elegans demonstrated
      by HPLC-fluorescene detection utilizing 7-chloro-N-[2-(dimethylamino)ethyl]-2,1,3
      benzoxadiazole-4-sulfonamide.
AB  - A highly sensitive and simple method using HPLC-fluorescence detection with 7
      chloro-N-[2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide (DAABD-Cl)
      as a fluorogenic reagent demonstrated the existence of the low-molecular-weight
      thiols in the extract of Caenorhabditis elegans (C. elegans). The method includes
      derivatization of the thiols with DAABD-Cl at 40 degrees C for 10 min in borate
      buffer (pH 9.0) containing TCEP, CHAPS and EDTA, separation of the derivatives on
      an ODS column and fluorometric determination of the derivatives at 510 +/- 15 nm
      with excitation at 400 +/- 15 nm. The identification of the thiols was made by
      HPLC-electrospray ionization mass spectrometry (LC-MS) following isolation of the
      derivatives using HPLC-fluorescence detection. Low-molecular-weight thiols were
      found to exist in the extract of C. elegans, such as cysteine, cysteinylglycine,
      gamma-glutamylcysteine, reduced glutathione and two other unidentified thiol
      compounds, confirming the existence of the 'glutathione cycle' in C. elegans
      similar to the mammalian body.

PMID- 17516465
TI  - Sacsin-related ataxia with neither retinal hypermyelination nor spasticity.

PMID- 17516466
TI  - Alterations in inorganic phosphate in mouse hindlimb muscles during limb disuse.
AB  - Muscle disuse induces a wide array of structural, biochemical, and neural
      adaptations in skeletal muscle, which can affect its function. We recently
      demonstrated in patients with an orthopedic injury that cast immobilization
      alters the resting P(i) content of skeletal muscle, which may contribute to loss
      of specific force. The goal of this study was to determine the direct effect of
      disuse on the basal phosphate content in skeletal muscle in an animal model,
      avoiding the confounding effects of injury/surgery. (31)P and (1)H MRS data were
      acquired from the gastrocnemius muscle of young adult mice (C57BL6 female, n =
      8), at rest and during a reversible ischemia experiment, before and after 2 weeks
      of cast immobilization. Cast immobilization resulted in an increase in resting
      P(i) content (75%; p < 0.001) and the P(i) to phosphocreatine (PCr) ratio
      (P(i)/PCr; 80%, p < 0.001). The resting concentrations of ATP, PCr and total
      creatine (PCr + creatine) and the intracellular pH were not significantly
      different after immobilization. During ischemia (30 min), PCr concentrations
      decreased to 54 +/- 2% and 52 +/- 6% of the resting values in pre-immobilized and
      immobilized muscles, respectively, but there were no detectable differences in
      the rates of P(i) increase or PCr depletion (0.55 +/- 0.01 mM min(-1) and 0.52 +/
      0.03 mM min(-1) before and after immobilization, respectively; p = 0.78). At the
      end of ischemia, immobilized muscles had a twofold higher phosphorylation
      potential ([ADP][P(i)]/[ATP]) and intracellular buffering capacity (3.38 +/- 0.54
      slykes vs 6.18 +/- 0.57 slykes). However, the rate of PCr resynthesis (k(PCr))
      after ischemia, a measure of in vivo mitochondrial function, was significantly
      lower in the immobilized muscles (0.31 +/- 0.04 min(-1)) than in pre-immobilized
      muscles (0.43 +/- 0.04 min(-1)). In conclusion, our findings indicate that 2
      weeks of cast immobilization, independent of injury-related alterations, leads to
      a significant increase in the resting P(i) content of mouse skeletal muscle. The
      increase in P(i) with muscle disuse has a significant effect on the cytosolic
      phosphorylation potential during transient ischemia and increases the
      intracellular buffering capacity of skeletal muscle.

PMID- 17516467
TI  - Video analysis of motor events in REM sleep behavior disorder.
AB  - In REM sleep behavior disorder (RBD), several studies focused on
      electromyographic characterization of motor activity, whereas video analysis has
      remained more general. The aim of this study was to undertake a detailed and
      systematic video analysis. Nine polysomnographic records from 5 Parkinson
      patients with RBD were analyzed and compared with sex- and age-matched controls.
      Each motor event in the video during REM sleep was classified according to
      duration, type of movement, and topographical distribution. In RBD, a mean of 54
      +/- 23.2 events/10 minutes of REM sleep (total 1392) were identified and visually
      analyzed. Seventy-five percent of all motor events lasted <2 seconds. Of these
      events, 1,155 (83.0%) were classified as elementary, 188 (13.5%) as complex
      behaviors, 50 (3.6%) as violent, and 146 (10.5%) as vocalizations. In the control
      group, 3.6 +/- 2.3 events/10 minutes (total 264) of predominantly elementary
      simple character (n = 240, 90.9%) were identified. Number and types of motor
      events differed significantly between patients and controls (P < 0.05). This
      study shows a very high number and great variety of motor events during REM sleep
      in symptomatic RBD. However, most motor events are minor, and violent episodes
      represent only a small fraction.

PMID- 17516468
TI  - Precolumn fluorescence labeling method for simultaneous determination of
      hydroxyzine and cetirizine in human serum.
AB  - A highly selective and sensitive method was developed for simultaneous
      determination of the antihistaminic drug hydroxyzine (HZ) and its
      pharmacologically active metabolite cetirizine (CZ) in human serum using
      haloperidol as internal standard. The method was based on fluorescence labeling
      of both drugs with a fluorescent arylboronic acid 4-(4,5-diphenyl-1H-imidazol-2
      yl)phenyl boronic acid followed by separation on silica column using a mobile
      phase consisting of acetonitrile and water (90:10, v/v%) containing triethylamine
      and acetic acid. The labeling reaction conditions were optimized and the liquid
      liquid extraction method was successfully applied to extract the both drugs from
      serum. The linearity range was 0.025-2.00 microg/mL for HZ and CZ. The limit of
      detection (S/N = 3) was 10 and 5 ng/mL for HZ and CZ, respectively.

PMID- 17516469
TI  - Porphomethene inhibitor of uroporphyrinogen decarboxylase: analysis by high
      performance liquid chromatography/electrospray ionization tandem mass
      spectrometry.
AB  - An uroporphomethene inhibitor of uroporphyrinogen decarboxylase, characterized by
      high-performance liquid chromatography/electrospray ionization tandem mass
      spectrometry, was reported recently (Phillips et al., Proceedings of the National
      Academy of Sciences of the United States of America 2007; 104: 5079-5084). Close
      examination of the tandem mass spectrometric fragmentation pattern of the
      compound showed that it is not a tetrapyrrole or an uroporphyrinogen or
      uroporphyrin related molecule. The product ion spectrum showed a fragmentation
      pattern typical of a poly(ethylene glycol) structure. Characteristic
      fragmentations of the side-chain acetic acid and propionic acid substituents of a
      uroporphyrin or uroporphyrinogen derivative were absent.

PMID- 17516470
TI  - Indirect resolution of enantiomers of penicillamine by TLC and HPLC using
      Marfey's reagent and its variants.
AB  - TLC and HPLC methods were developed for indirect chiral separation of
      penicillamine (3,3-dimethylcysteine) enantiomers after derivatization with
      Marfey's reagent (FDNP-Ala-NH(2)) and two of its structural variants, FDNP-Phe
      NH(2) and FDNP-Val-NH(2). The binary mobile phase of phenol-water (3:1 v/v) and
      solvent combinations of acetonitrile and triethylamine phosphate buffer were
      found to give the best separation in normal and reversed-phase TLC, respectively.
      The diastereomers were also resolved on a reversed-phase C18 HPLC column with
      gradient elution of acetonitrile and 0.01 m trifluoroacetic acid. The results due
      to these three reagents were compared. The method was successful for checking the
      enantiomeric impurity of l-penicillamine in d-penicillamine and to check the
      enantiomeric purity of pharmaceutical formulations of d-penicillamine. The method
      was validated for linearity, repeatability, limit of detection and limit of
      quantification.

PMID- 17516471
TI  - Antineuronal antibody status and phenotype analysis in Tourette's syndrome.
AB  - The Gilles de la Tourette syndrome (GTS) spectrum includes psychiatric
      comorbidities, mainly obsessive-compulsive disorder (OCD) and attention-deficit
      hyperactivity disorder (ADHD). The role of environmental factors, e.g.,
      antineuronal antibodies (ANeA), remains unclear. We compared the clinical
      features of ANeA-positive and ANeA-negative patients in 53 children and 75 adults
      with GTS. All diagnoses were made according to DSM-IV-TR criteria. A positive
      ANeA Western immunoblot showed bands for at least 1 of 3 reported striatal
      antigens (40, 45, and 60 kDa). Twelve children (23%) and 18 adults (25%) with GTS
      were ANeA-positive. Disease duration, tic phenomenology and severity, frequency
      of echo/pali/coprophenomena, self-injurious and aggressive behavior, or frequency
      of OCD comorbidity did not significantly differ between ANeA-positive and
      negative patients. Similar findings were obtained analyzing separately the three
      different antibody reactivities. A comorbid diagnosis of ADHD was significantly
      less frequent in GTS patients positive for the anti-60 kDa antibody only. Using a
      multivariate logistic regression model, adjusting for age, gender, and age at
      disease onset, a comorbid diagnosis of ADHD remained inversely associated with
      anti-60 kDa antibodies (odds ratio = 0.14; P = 0.002; 95% confidence interval
      0.04-0.49). ANeA status does not differentiate a specific phenotype of GTS.

PMID- 17516472
TI  - Repetitive transcranial stimulation for freezing of gait in Parkinson's disease.

PMID- 17516473
TI  - Heterogeneity of presentation and outcome in the Irish rapid-onset dystonia
      parkinsonism kindred.
AB  - The authors report a 7-year follow-up video study and molecular data on the Irish
      rapid-onset dystonia-Parkinsonism kindred. All affected patients tested had a
      missense mutation in the Na(+)/K(+) -ATPase alpha3 subunit (ATP1A3), twice
      previously identified, suggestive of a mutation hotspot. Clinical presentation,
      progression, and outcome in this kindred is varied. Some patients remain stable
      over many years, others worsen, have a fluctuating course, or improve over time.
      To date there have been no effective treatments for this disorder, although
      Na(+)/K(+) ATPase may be a future therapeutic target. The broad phenotypic
      spectrum of RDP described in the text and detailed in the video, should be
      considered when evaluating patients with dystonia.

PMID- 17516474
TI  - Adult-onset dystonia: atypical manifestation of Segawa disease.
AB  - A 33-year-old woman developed exercise-induced limb and trunk dystonia with
      marked diurnal fluctuations. Treatment with levodopa improved her symptoms
      considerably but incompletely. Molecular genetic analysis revealed a mutation in
      GTP cyclohydrolase 1 (GCH1). This report illustrates the variability of Segawa
      disease and underlines the importance of a levodopa test in patients with
      uncommon dystonic symptoms.

PMID- 17516475
TI  - Prevalence of essential tremor in patients with Parkinson's disease vs. Parkinson
      plus syndromes.
AB  - Clinical literature suggests an association between essential tremor (ET) and
      Parkinson's disease (PD), and recent pathological studies describe Lewy bodies in
      some ET patients. If some ET were an expression of Lewy body disease, one could
      hypothesize that ET patients who develop parkinsonism would more likely develop
      PD (a Lewy body disease) than non-Lewy body forms of parkinsonism. The objective
      was to compare the proportions of patients with PD vs. Parkinson-plus syndromes
      who had diagnoses of ET. Retrospective chart review at the Neurological Institute
      (NI) of New York. A larger proportion of the 210 PD than 210 Parkinson-plus
      syndrome patients had kinetic tremor on examination (119 [56.7%] vs. 70 [33.3%],
      P < 0.001). Patients with PD were more likely to have a prior diagnosis of ET
      than were patients with Parkinson-plus syndromes (7.1% vs. 2.4%, OR 3.16, 95% CI
      1.13-8.85, P = 0.02) and more likely to have a diagnosis of ET assigned by an NI
      neurologist (5.3% vs. 0.0%, OR 12.85, 95% CI 1.66-99.8, P = 0.001). Patients with
      PD were three to thirteen times more likely to have diagnoses of ET than were
      patients with Parkinson-plus syndromes. These data further confirm the link
      between ET and PD, and possibly, between ET and Lewy body disease.

PMID- 17516476
TI  - Efficacy and complication of botulinum toxin injection in palatal myoclonus:
      experience from a patient.
AB  - We report the outcome of botulinum toxin injection for essential palatal
      myoclonus, given on two occasions over a period of one year, in an eight-year-old
      boy, the youngest patient treated with botulinum toxin to date. Though there was
      significant relief of ear clicks each time after the injection, he developed
      severe palatal palsy following the second injection, which persisted for a month.
      We suggest that appropriate caution needs to be exercised when repeating
      botulinum toxin injections for palatal myoclonus in children.

PMID- 17516477
TI  - Oral festination in Parkinson's disease: biomechanical analysis and correlation
      with festination and freezing of gait.
AB  - In Parkinson's disease (PD), festination corresponds to a tendency to speed up
      when performing repetitive movements. First described in gait (and then in
      handwriting and speech), festination is one of the most disabling axial symptoms.
      To establish the phenomenology of oral festination (OF) and the condition's
      potential links with other axial disorders, we submitted a simple, rhythmic,
      repetitive, vocal motor task to 40 PD patients and 20 controls. Forty-five
      percent of the 40 patients presented OF, which was strongly associated with gait
      festination but not with the severity of freezing of gait (FOG) or dysarthria.
      With respect to the two pathophysiological hypotheses that have been put forward,
      a possible link with tremor (as previously suggested in tapping) was not
      confirmed in this study and so, in view of the significant increase in
      variability observed, we conclude that OF shares the same pathophysiology as gait
      disorders.

PMID- 17516478
TI  - Risk of incident dementia in essential tremor: a population-based study.
AB  - Essential tremor (ET) is a late-life neurological disease. Mild cognitive
      deficits as well as an association with prevalent dementia have been reported in
      recent case-control studies. We determined whether ET was associated with an
      increased risk of incident dementia. In a population-based study of older people
      in central Spain (NEDICES), nondemented ET cases and controls were followed
      prospectively. Incident dementia at follow-up was diagnosed using DSM-IV criteria
      and the risk of incident dementia was estimated in ET cases versus controls using
      Cox proportional hazards models. 3,891 participants had a mean duration of follow
      up of 3.2 years. Sixteen (7.8%) of 206 ET cases developed incident dementia
      versus 145 (3.9%) of 3,685 controls (unadjusted relative risk [RR]=2.08, 95%
      CI=1.24-3.50, P=0.006 and adjusted RR=1.66, 95% CI=0.99-2.80, P=0.054). In an
      adjusted model, ET cases with tremor onset after age 65 years were twice as
      likely to develop incident dementia than were controls (RR=1.98, 95% CI=1.14
      3.45, P=0.01), whereas ET cases with tremor onset<age 65 years and controls were
      equally to develop incident dementia (RR=0.74, 95% CI=0.19-3.20, P=0.79).
      Although ET is often considered a benign condition, in this prospective,
      population-based study, elderly-onset ET was associated with an increased risk of
      incident dementia. The basis for this dementia, which is not known, requires
      additional study.

PMID- 17516479
TI  - Determinants of quality of life in Brazilian patients with Parkinson's disease.
AB  - Our objective was to identify determinants of health-related quality of life
      (HRQoL) in a cohort of Brazilian patients with Parkinson's disease (PD). Patients
      were evaluated by means of the Hoehn and Yahr staging (H&Y), Unified Parkinson's
      Disease Rating Scale (UPDRS), Schwab and England scale (S&E), Mini-Mental State
      Exam, Geriatric Depression Scale, and Hospital Anxiety and Depression Scale
      (HADS). HRQol was assessed using the MOS-Short-Form 36 (SF-36), the Parkinson's
      disease Questionnaire (PDQ-39), and the Scales for Outcomes in Parkinson's
      Disease-Psychosocial Questionnaire (SCOPA-PS). 144 patients were evaluated (mean
      age 62 years; 53.5% men; mean duration of illness 6.6 years; median H&Y, 2
      (range: 1-4). Mean SCOPA-PS and PDQ-39 Summary Index (SI) were 39.2 and 40.7,
      respectively. Both, PDQ-39 and SCOPA-PS SIs correlated at a moderate level (r =
      0.30-0.50) with H&Y, S&E, total UPDRS, HADS subscales, and SF-36 Physical and
      Mental Components. PDQ-39 and SCOPA-PS were closely associated (r = 0.73). HRQoL
      significantly deteriorated as H&Y progressed, as a whole. Mood disturbances,
      disability, motor complications, and education were independent predictors of
      HRQoL in the multivariate analysis model. In PD Brazilian patients, HRQoL
      correlated significantly with diverse measures of severity. Depression showed to
      be the most consistent determinant of HRQoL, followed by disability, motor
      complications, and education years. There was a close association between the PDQ
      39 and SCOPA-PS summary scores.

PMID- 17516480
TI  - Hemimasticatory spasm following pontine infarction.

PMID- 17516481
TI  - Huntington's disease like-2 neuropathology.
AB  - Huntington's disease like-2 (HDL-2) neurodegeneration is a recently described
      autosomal dominant disorder with features similar to Huntington's disease (HD).
      Only one case report has described neuropathology from an affected patient. We
      describe the clinical presentation and illustrate the pathology in two additional
      molecularly confirmed patients, compare these with the previously published case,
      and contrast them with HD. We examined two patients with HDL-2. Their charts were
      reviewed, their brains were examined using standard neuropathology techniques,
      including immunoperoxidase stains, and their diagnoses were confirmed with a PCR
      based assay for repeat length. The first patient presented with obsessive
      suspiciousness, while the second had depression and decreased visual acuity. Both
      patients developed increased tone and cogwheel rigidity, but neither developed
      choreoathetosis. Extensive degeneration affected the caudate nucleus and putamen,
      especially dorsally and laterally. In addition, the first patient showed lateral
      temporal, lateral frontal, and orbitofrontal cortical atrophy, while the second
      patient displayed marked degeneration in the occipital and parietal cortices.
      Neither patient showed significant changes in the cerebellum or brainstem. Both
      cases had ubiquitin-immunoreactive neuronal intranuclear inclusions (NII). The
      patients with of HDL-2 reviewed here were remarkable for significant frontal
      inhibition with parkinsonism, a lack of choreiform movements, and African
      ancestry. Pathologically, HDL-2 is similar to HD in its effect on the neostriatum
      but may differ, at least in some cases, in its degree of focal cortical
      involvement, including the occipital lobe.

PMID- 17516482
TI  - Epileptic myoclonus as ciprofloxacin-associated adverse effect.

PMID- 17516483
TI  - Thirty days complication rate following surgery performed for deep-brain
      stimulation.
AB  - Serious adverse events (SAEs) during the first 30 postoperative days after
      stereotactic surgery for Deep-Brain-Stimulation performed in 1,183 patients were
      retrospectively collected from five German stereotactic centers. The mortality
      rate was 0.4% and causes for death were pneumonia, pulmonary embolism,
      hepatopathy, and a case of complicated multiple sclerosis. The permanent surgical
      morbidity rate was 1%. The most frequently observed SAEs were intracranial
      hemorrhage (2.2%) and pneumonia (0.6%). Skin infection occurred in 5 of 1,183
      patients (0.4%). Surgical complications caused secondary AEs (e.g. pneumonia)
      preferentially in older patients and in patients treated for Parkinson's disease
      (PD). Complication rates did not differ among the five centers.

PMID- 17516484
TI  - Efficacy and tolerability of Entacapone versus Cabergoline in parkinsonian
      patients suffering from wearing-off.
AB  - In this 12-wk, multi-center, randomized, open-label, rater-blinded study,
      efficacy and tolerability of Entacapone (ENT) or Cabergoline (CBG) in conjunction
      with levodopa were compared in 161 older Parkinson's disease patients with
      wearing-off. Patients received either ENT, 3 to 5 times daily, or CBG, titrated
      according to requirements to a maximum of 6 mg/d. A significant decrease of
      nearly 2 hours in the daily OFF-time (primary efficacy variable) was recorded in
      both treatment groups. The non-inferiority test failed despite a trend in favor
      of ENT. Reduction in OFF-time occurred faster in the ENT compared to the CBG
      treated patients. A decrease of approximately 20% was detected in parts II and
      III of the UPDRS, with no differences between the groups. Forty-three percent of
      the patients in the ENT group reported dyskinesias at baseline, and 35% at the
      final visit. The corresponding figures in the CBG group were 46% and 43%. Quality
      of life, measured by PDQ-39, increased substantially with both ENT and CBG. The
      mean daily dosage at the final visit was 698 mg for ENT (plus 447 mg levodopa)
      and 3.45 mg for CBG (plus 475 mg levodopa). Adverse events (AE), leading to
      discontinuation, were reported in 8.5% of the ENT and 13.9% of the CBG treated
      patients. Nausea was the most common AE in each group, corresponding figures
      being 7.3% with ENT and 25.3% with CBG (P=0.0024). A probable or possible causal
      relationship with ENT was reported in 41% and with CBG in 64% of the AE. Among
      these, only one serious AE (dehydration) was recorded with each treatment group.
      ENT and CBG reduced the patient's motor complications effectively and to a
      similar degree. The clinical benefit was more quickly apparent with ENT, which
      also showed a more favorable AE profile than CBG.

PMID- 17516485
TI  - Body weight in patients with Parkinson's disease.

PMID- 17516486
TI  - Silas Weir Mitchell's essential tremor.
AB  - Silas Weir Mitchell (1829-1914) is recognized as an important American
      neurologist. Biographers refer in brief to a tremor. The objective of this review
      was to characterize Mitchell's tremor using handwriting samples, to examine
      handwriting samples of family members to determine whether this tremor was
      familial, and study Mitchell's allusions to tremor in personal, scientific, and
      fictional writings. Primary sources were the Papers of S. Weir Mitchell, College
      of Physicians of Philadelphia, and Mitchell's scientific and fictional writings.
      Mitchell's early handwriting was tremor-free yet, by 1873, the writing was
      tremulous. Handwriting in the 1880s and 1890s shows clear oscillations of
      moderate-amplitude. By the first decade of the 20th century, his handwriting was
      virtually illegible. Letters written by two siblings, his mother, and maternal
      grandfather also reveal tremor. Tremor was not prominent in Mitchell's personal
      or scientific writings and Mitchell referred to tremor in only 4 of 27 fictional
      writings. In conclusion, Mitchell had a familial action tremor that began when he
      was in his early 40's and worsened considerably with age. The likely diagnosis
      was essential tremor. Curiously, Mitchell rarely alluded to tremor in personal
      writings and tremor was not prominently featured in his scientific or fictional
      works.

PMID- 17516487
TI  - Patient selection and assessment recommendations for deep brain stimulation in
      Tourette syndrome.

PMID- 17516488
TI  - Pathophysiological concepts of restless legs syndrome.
AB  - Pathophysiological concepts of restless legs syndrome (RLS) are based mainly on
      neuroimaging and on neurophysiological data. Furthermore treatment effects
      contribute essentially to the present understanding of the disease, unless the
      genetic progress expected in the near future will clarify substantially open
      issues. The concept agreed on assumes a dysfunction of the dopaminergic system,
      possibly on the level of striatal and/or spinal dopamine receptors, and the A11
      neuron group localized in the hypothalamus as an integrated part of the system.
      These neurons modulate spinal excitability, alterations of which in turn affect
      sensory processing predominantly of leg afferents in brain stem structures.
      Neurophysiologically excitability alterations can be measured by a variety of
      methods such as determination of pain thresholds, H-reflex testing, and
      quantitative sensory testing.

PMID- 17516489
TI  - The suitability of patient-based measures in the field of Parkinson's disease: a
      systematic review.
AB  - The aim of this study is to appraise the suitability of current quality of life
      (QOL) questionnaires for use in the field of Parkinson's disease (PD).
      Computerized bibliographic databases were screened for publications from 1960 to
      December 2006. Predefined selection criteria were used to identify QOL
      questionnaires in PD studies. Two investigators independently assessed and,
      subsequently, agreed on a set of multidimensional generic and PD-specific QOL
      questionnaires. Data were extracted concerning the internal structure,
      reliability, validity, and responsiveness of the included questionnaires. Sixteen
      questionnaires were found, of which 14 questionnaires were included (six generic
      measures and eight PD-specific). In general, the psychometrics of all the
      questionnaires were adequately described. Sensitivity to change, however, has
      been reported for only a limited number of instruments. Almost all included
      questionnaires used QOL as a keyword, but only two questionnaires fitted the
      broad QOL definition used in this review. Considering the few "real " QOL
      questionnaires, we conclude that there is a strong need for such instruments.

PMID- 17516490
TI  - NMR spectroscopy of aminoacylase 1 deficiency, a novel inborn error of
      metabolism.
AB  - Aminoacylase 1 deficiency is a novel inborn error of metabolism. The clinical
      significance of the deficiency is under discussion, as well as the possible
      consequences of the defect for brain metabolism and function. This study includes
      the five originally published cases as well as three novel ones. NMR spectroscopy
      of urine, serum and cerebrospinal fluid has been used to study these patients. A
      typical profile with 11 accumulating N-acetylated amino acids was observed in
      urine from the patients. The concentration of most of the accumulating
      metabolites is typically 100-500 micromol/mmol creatinine. Two additional minor N
      acetylated metabolites remain unidentified. The concentrations of the
      accumulating metabolites are <20 micromol/L in serum from the patients.
      Interestingly we found no evidence of an increased concentration of N-acetylated
      amino acids in the cerebrospinal fluid from one patient. Our data define
      aminoacylase 1 deficiency at the metabolite level providing a specific urinary
      profile of accumulating N-acetylated amino acids.

PMID- 17516491
TI  - Fast screening of paramagnetic molecules in zebrafish embryos by MRI.
AB  - Zebrafish embryo is a well-established model used in many fields of modern
      experimental biology. We demonstrate that it provides a promising model platform
      for exploring fundamental MR aspects that can be used to screen and study active
      MR molecules before progressing to more complex living systems. Setting up a
      dedicated MRI methodology, we arrayed a large number of living embryos, which
      were microinjected at very early stages of development with different contrast
      agents. We also showed that MRI signal intensity correlates with the gadolinium
      content of zebrafish embryos. This allowed us to validate a new approach for MR
      compound screening. Using a specific surface coil of 5 mm inner diameter, we
      obtained for the first time high-spatial-resolution images at 7 T of living
      zebrafish embryos with a 47 microm isotropic voxel size with an acquisition time
      of 39 min. Finally, we discuss potential applications of this development: a
      viable in vivo assay for screening small pharmacological compounds; assessment of
      and tracking the action of molecules over time. Exploring in vivo biological
      activity, gene function analysis, and detailed characterization of disease
      processes in fish are natural extensions of these preliminary studies.

PMID- 17516492
TI  - Bright light therapy in Parkinson's disease: a pilot study.
AB  - Several observations suggest a beneficial effect of melatonin antagonism for
      Parkinson's disease (PD). Although bright light therapy (BLT) suppresses
      melatonin release and is an established treatment for depression and sleep
      disturbances, it has not been evaluated in PD. We examined effects of BLT on
      motor symptoms, depression, and sleep in PD in a randomized placebo-controlled
      double-blind study in 36 PD patients, using Parkinson's Disease Rating Scale
      (UPDRS) I-IV, Beck's Depression Inventory, and Epworth Sleepiness Scale. All
      patients received BLT for 15 days in the morning, 30 min daily. Illuminance was
      7.500 lux in the active treatment group and 950 lux in the placebo group.
      Although group differences were small, BLT led to significant improvement of
      tremor, UPDRS I, II, and IV, and depression in the active treatment group but not
      in the placebo group. It was very well tolerated. Follow up studies in more
      advanced patient populations employing longer treatment durations are warranted.

PMID- 17516493
TI  - Reliability and validity of the scale for the assessment and rating of ataxia: a
      study in 64 ataxia patients.
AB  - The objective of this study was to test the reliability and validity of the Scale
      for the Assessment and Rating of Ataxia (SARA) in ataxia patients not suffering
      from autosomal dominant spinocerebellar ataxia (SCA). To this end, 64 patients
      with various ataxia disorders or stable cerebellar lesions were rated
      independently by two investigators. In addition to SARA, the following assessment
      instruments were applied: ataxia disease stage, Barthel index and part IV
      (functional assessment) of the Unified Huntington's Disease Rating scale (UHDRS
      IV). Eighteen patients were rated twice. Inter-rater and intrarater reliability
      were very high with ICCs of 0.98 and 0.99. Internal consistency was high
      indicated by Cronbach's alpha of 0.97. Factorial analysis revealed that the
      rating results were mainly determined by one major factor with an eigenvalue of
      6.34 which explained 52.8% of the variance. SARA score increased with disease
      stage (P<0.0001) and was closely correlated with Barthel index (r=-0.63,
      P<0.0001) and UHDRS-IV (r=-0.62, P<0.0001), but only weakly correlated with
      disease duration (r=0.44, P<0.001). The results suggest that SARA is a reliable
      and valid measure of ataxia in non-SCA ataxia patients.

PMID- 17516494
TI  - Expanding the phenotype of fragile X-associated tremor/ataxia syndrome: a new
      female case.

PMID- 17516495
TI  - Defined protein and animal component-free NS0 fed-batch culture.
AB  - A chemically defined protein and animal component-free fed-batch process for an
      NS0 cell line producing a human IgG(1) antibody has been developed. The fed-batch
      feed profile was optimised in a step-wise manner. Depletion of measurable
      compounds was determined by direct analysis. The cellular need for non-measurable
      compounds was tested by continued culturing of cell suspension, removed from the
      bioreactor, in shake-flasks supplemented with critical substances. In the final
      fed-batch culture, 8.4 x 10(6) viable cells mL(-1) and 625 mg antibody L(-1) was
      obtained as compared to 2.3 x 10(6) cells mL(-1) and 70 mg antibody L(-1) in
      batch. The increase in cell density, in combination with a prolonged declining
      phase where antibody formation continued, resulted in a 6.2-fold increase in
      total cell yield, a 10.5-fold increase in viable cell hours and an 11.4-fold
      increase in product yield. These improvements were obtained by using a feed with
      glucose, glutamine, amino acids, lipids, sodium selenite, ethanolamine and
      vitamins. Specifically, supplementation with lipids (cholesterol) had a drastic
      effect on the maximum viable cell density. Calcium, magnesium and potassium were
      not depleted and a feed also containing iron, lithium, manganese, phosphorous and
      zinc did not significantly enhance the cell yield. The growth and death profiles
      in the final fed-batch indicated that nutrient deprivation was not the main cause
      of cell death. The ammonium concentration and the osmolality increased to
      potentially inhibitory levels, but an imbalance in the supply of growth/survival
      factors may also contribute to termination of the culture.

PMID- 17516496
TI  - Skin cancers and precancerous lesions in Parkinson's disease patients.
AB  - Our objective was to evaluate the frequency of neoplastic and preneoplastic skin
      lesions in Parkinson's disease (PD) patients when compared with an aged-matched
      population. We performed a cross-sectional survey in PD patients and in an age
      matched control group. Patients and controls were examined by a movement disorder
      specialist and a dermatologist. 150 PD patients and 146 controls were included.
      Thirty-five PD patients (23.3%) presented skin lesions that could be classified
      as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR
      95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical
      significance when adjusted for gender (recruitment of controls was matched just
      for age with an over representation of males in the PD group). Twenty-nine PD
      patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed
      in 4 patients (3%). Although nonconclusive, our results are in agreement with
      previous studies suggesting an increased risk of skin cancer in PD patients. The
      frequency of actinic keratosis in PD patients and the associated risk to develop
      melanoma recommends its screening in future epidemiological studies.

PMID- 17516497
TI  - Impaired cardiovascular autonomic function in Parkinson's disease with visual
      hallucinations.
AB  - We assessed the relations of visual hallucinations (VH) to cardiovascular
      autonomic dysfunction in patients with Parkinson's disease (PD). The subjects
      were 37 patients without VH (VH(-)) and 31 with VH (VH(+)). Autonomic function
      was evaluated on the basis of cardiac 123-radioiodinated metaiodobenzylguanidine
      (123I-MIBG) uptake and hemodynamic testing with Valsalva maneuver. Systolic blood
      pressure (SBP) and plasma norepinephrine concentrations (NE) were measured by
      tilt-table testing. 123I-MIBG uptake was lower in VH(+) than VH(-). Hemodynamic
      studies showed that VH(-) had only cardiac sympathetic and parasympathetic
      dysfunction, while VH(+) additionally had reduced vasomotor sympathetic
      functions. The fall in SBP during tilt-table testing was greater in VH(+) than
      VH(-). NE and its difference in the supine and upright positions were decreased
      in VH(+). We conclude that cardiac and vasomotor sympathetic dysfunction is more
      severe in VH(+) than in VH(-). Severe dysfunction in PD with VH is probably
      attributed to Lewy-body lesions or neuronal loss in sympathetic ganglia, the
      central autonomic system, or both.

PMID- 17516498
TI  - HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cells.
AB  - Cell surface heparan sulfate proteoglycans (HSPGs) play important roles in
      morphogen gradient formation and cell signaling. Bone morphogenetic protein (BMP)
      signaling is dysregulated in fibrodysplasia ossificans progressiva (FOP), a
      disabling disorder of progressive heterotopic bone formation. Here, we
      investigated the role of HSPG glycosaminoglycan (GAG) side chains on BMP
      signaling and found increased total and HSPG-specific GAG chain levels and
      dysregulation in HSPG modulation of BMP signaling in FOP lymphoblastoid cells
      (LCLs). Specifically, HSPG profiling demonstrated abundant mRNA and protein
      levels of glypican 1 and syndecan 4 on control and FOP LCLs, with elevated core
      protein levels on FOP cells. Targeted downregulation of glypican 1 core protein
      synthesis by siRNA enhanced BMP signaling in control and FOP cells, while
      reduction of syndecan 4-core protein synthesis decreased BMP signaling in
      control, but not FOP cells. These results suggest that FOP cells are resistant to
      the stimulatory effects of cell surface HSPG GAG chains, but are susceptible to
      the inhibitory effects, as shown by downregulation of glypican 1. These data
      support that HSPG modulation of BMP signaling is altered in cells from patients
      with FOP and that altered HSPG-related BMP signaling may play a role in the
      pathogenesis of the disease.

PMID- 17516499
TI  - The structure of the TGF-beta latency associated peptide region determines the
      ability of the proprotein convertase furin to cleave TGF-betas.
AB  - The TGF-beta family members are generated as latent pre-pro-polypeptides. The
      active mature peptides are cleaved from the latent forms by cellular proteases.
      TGF-beta 1, for instance, is predominantly processed by a substilisin-like
      proprotein convertase, furin. TGF-beta 2 has a consensus cleavage site for furin
      and therefore has been presumed to be cleaved by furin. However, TGF-beta 2 is
      often secreted as the latent form, which appears to be inconsistent with its
      postulated sensitivity to furin. We report here that both the regular (short)
      form of TGF-beta2 and its spliced variant with an additional exon (long form) are
      insensitive to furin. NIH 3T3 and CHO cells were transfected with expression
      vectors containing the short or long form of TGF-beta 2 or a chimeric TGF-beta
      consisting of the TGF-beta1 LAP region, the TGF-beta 2 cleavage site and the TGF
      beta 2 mature peptide. The constructs included a c-myc epitope tag in the N
      terminal region of the mature peptide. The TGF-betas produced by the transfected
      cells were analyzed with Western blots and immunocytochemistry. The intracellular
      proteins harvested from these cells were incubated with furin. Furin only
      inefficiently cleaved both the long and short forms of TGF-beta 2, but
      efficiently processed the chimeric TGF-beta. This indicates that the
      insensitivity of both forms of TGF-beta 2 to furin is a consequence of the
      tertiary structure of their LAP regions rather than their cleavage site. This
      differential processing of TGF-beta1 and -beta 2 may be part of the mechanism
      that generates isoform-specific functions of the TGF-betas.

PMID- 17516500
TI  - Effect of repetition rate on the formation of microtears in tendon in an in vivo
      cyclical loading model.
AB  - We reported previously the formation of microtears in an in vivo loaded Flexor
      Digitorum Profundus (FDP) rabbit tendon with a repetition rate of 60 repetitions
      per minute and a peak force of 15% of maximum peak tetanic force for 80
      cumulative hours. Tear area as a percent of tendon area, tear density
      (tears/mm(2)), and mean tear size (microm(2)) were higher in tendons from the
      loaded limb compared to the unloaded control limb. The purpose of the present
      study was to compare those results to results obtained with a repetition rate of
      10 while maintaining the same peak force and force-time integral (n = 8). Due to
      a strain gradient between the inner and outer sides of the FDP tendon, microtears
      were quantified in four regions, two regions each along the inner and outer sides
      of the tendon. The tear area as a percent of total tendon area and the mean tear
      size were significantly greater in the loaded limb compared to the unloaded limb
      (p < 0.03). However, the effects were less than those observed at 60
      repetitions/min. The higher repetition loading pattern resulted in an increase in
      tear measures in all four regions, while the lower rate produced changes only in
      the outer regions of the tendon. This finding may establish where the initial
      sites of damage occur in tendons that insert into bone in a similar arrangement
      as the FDP. The results suggest that repetition rate or number of loading cycles
      is associated with increased tendon microtears or fragility in a dose-response
      pattern.

PMID- 17516501
TI  - Development and iron-dependent expression of hephaestin in different brain
      regions of rats.
AB  - It has been suggested that Hephaestin (Heph), a newly discovered ceruloplasmin
      homologue, is necessary for iron egress from the enterocytes into circulation via
      interacting with ferroportin1 (FP1). Based on the putative function of Heph, and
      the similarity between the process of iron transport in the enterocytes and that
      in the blood-brain barrier (BBB) cells, it has also been proposed that Heph plays
      a similar role in exporting iron from the BBB cells and other brain cells as it
      works in the enterocytes via interacting with FP1. The existence of FP1 in the
      brain has been demonstrated. In this study, we investigated Heph expression and
      effects of development and iron in the cortex, hippocampus, striatum, and
      substantia nigra. The data demonstrated that all the four regions we examined
      have the ability to express Heph mRNA and protein. The findings also showed that
      both the development and iron status have a significant effect on Heph expression
      and the effects of iron status are regionally specific. It was also suggested
      that Heph expression is probably regulated at the transcriptional level by the
      development and iron in these brain regions. These findings, together with other
      published data, support a putative role of Heph in the iron metabolism in the
      brain.

PMID- 17516502
TI  - Study of solid-phase synthesis and purification strategies for the preparation of
      polyglutamine peptides.
AB  - Many neurodegenerative diseases are related to an abnormal expansion of the CAG
      trinucleotide that produces polyglutamine segments in several proteins. However,
      the pathogenesis of these neurodegenerative states is not yet well understood.
      Thus, to evaluate the molecular mechanisms leading to those diseases, suitable
      research tools such as synthetic polyglutamine peptides are required. The
      synthesis and purification of such peptides are usually difficult because of poor
      solubility, which leads to low coupling and/or deblocking reactivity. After
      exploring many synthesis, solubilization and purification approaches, a protocol
      allowing the production of polyglutamines in good yield and high purity was
      developed. With this protocol, peptides of 10-30 glutamine residues were
      synthesized using a linear solid-phase strategy combined with a maximal side
      chain protection scheme using fluorenylmethyloxycarbonyl (Fmoc) chemistry. After
      cleavage of the peptide from the polymeric support, the crude material was
      treated with glacial acetic acid and lyophilized. This treatment significantly
      improved the solubility of the polyglutamine peptides thus allowing their
      dissolution in aqueous conditions and purification through reverse-phase high
      performance liquid chromatography. These solubilization and purification
      conditions led to the formation of N-pyroglutamyl peptide derivatives that were
      easily isolated. These N-pyroglutamylated compounds also appear as useful
      research tools because data from the literature suggest that N-terminal
      modification of polyglutamine segments might play a role in their pathogenic
      properties.

PMID- 17516503
TI  - Merozoite surface protein 2 of Plasmodium falciparum: expression, structure,
      dynamics, and fibril formation of the conserved N-terminal domain.
AB  - Merozoite surface protein 2 (MSP2) is a GPI-anchored protein on the surface of
      the merozoite stage of the malaria parasite Plasmodium falciparum. It is largely
      disordered in solution, but has a propensity to form amyloid-like fibrils under
      physiological conditions. The N-terminal conserved region (MSP2(1-25)) is part of
      the protease-resistant core of these fibrils. To investigate the structure and
      dynamics of this region, its ability to form fibrils, and the role of individual
      residues in these properties, we have developed a bacterial expression system
      that yields > or =10 mg of unlabeled or (15)N-labeled peptide per litre of
      culture. Two recombinant versions of MSP2(1-25), wild-type and a Y7A/Y16A mutant,
      have been produced. Detailed conformational analysis of the wild-type peptide and
      backbone (15)N relaxation data indicated that it contains beta-turn and nascent
      helical structures in the central and C-terminal regions. Residues 6-21 represent
      the most ordered region of the structure, although there is some flexibility
      around residues 8 and 9. The 10-residue sequence (MSP2(7-16)) (with two Tyr
      residues) was predicted to have a higher propensity for beta-aggregation than the
      8-mer sequence (MSP2(8-15)), but there was no significant difference in
      conformation between MSP2(1-25) and [Y7A,Y16A]MSP2(1-25) and the rate of fibril
      formation was only slightly slower in the mutant. The peptide expression system
      described here will facilitate further mutational analyses to define the roles of
      individual residues in transient structural elements and fibril formation, and
      thus contribute to the further development of MSP2 as a malaria vaccine
      candidate.

PMID- 17516504
TI  - Cytoplasm-localized SIRT1 enhances apoptosis.
AB  - In general, SIRT1 is localized in nuclei. Here, we showed that endogenous and
      exogenous SIRT1 were both able to partially localize in cytoplasm in certain cell
      lines, and cytoplasm-localized SIRT1 was associated with apoptosis and led to
      increased sensitivity to apoptosis. Furthermore, we demonstrated that
      translocation of nucleus-localized SIRT1 from nuclei to cytoplasm was the main
      pathway leading to localization of SIRT1 in cytoplasm. In HeLa cells, wild type
      SIRT1 was completely localized in nuclei. By truncation of two predicted nuclear
      localization signals or fusion with an exogenous nuclear export signal, SIRT1 was
      partially localized in cytoplasm of HeLa cells and resulted in increased
      sensitivity to apoptosis. The apoptosis enhanced by cytoplasm-localized SIRT1 was
      independent of its deacetylase activity, but dependent on caspases. SIRT1 was
      distributed in cytoplasm at metaphase during mitosis, and overexpression of SIRT1
      significantly augmented apoptosis for cells at metaphase. In summary, we found
      SIRT1 is able to localize in cytoplasm, and cytoplasm-localized SIRT1 enhances
      apoptosis.

PMID- 17516505
TI  - Sp1 and Smad3 are required for high glucose-induced p21(WAF1) gene transcription
      in LLC-PK1 cells.
AB  - The cyclin-dependent kinase inhibitor p21(WAF1) is required for diabetic
      glomerular hypertrophy. High glucose-induced hypertrophy in proximal tubule cells
      is dependent on transforming growth factor-beta (TGF-beta). Many of the TGF-beta
      induced effects are dependent on Smad2/3. Thus, the molecular mechanisms of high
      glucose-induced p21(WAF1) and hypertrophy were studied in high glucose-cultured
      proximal tubule-like LLC-PK(1) cells. We found that high glucose (30 mM) induced
      hypertrophy at 72 h. High glucose also increased the expression of p21(WAF1)
      protein and p21(WAF1) mRNA transcription and abundance at 48 h. The DNA element
      in the 5' regulatory region of p21(WAF1) gene essential for high glucose-induced
      p21(WAF1) gene transcription was identified as Sp1 by a series of the 5'
      regulatory region of p21(WAF1) gene deletion mutants. Moreover, high glucose
      activated Smad2/3 while increasing the Sp1 DNA-binding activity. High glucose
      also increased the Sp1-dependent transcriptional activity of p21(WAF1) gene. High
      glucose-induced hypertrophy was attenuated by p21(WAF1) short interfering RNA and
      Smad3 dominant-negative plasmid transfection. We concluded that high glucose
      induced hypertrophy via Sp1-Smad2/3-dependent activation of p21(WAF1) gene
      transcription in LLC-PK(1) cells.

PMID- 17516506
TI  - Effects of 120 mT static magnetic field on TGF-beta1-inhibited endothelial
      tubular formation in vitro.
AB  - We designed this study to examine the effects of static magnetic fields (SMF; 120
      mT [B(max)] and a maximum spatial magnetic flux gradient of 21 mT/mm) on
      inhibited tubular formation when treated with human transforming growth factor
      (TGF)-beta1 at a relatively high concentration (5 ng/ml). Three experimental
      groups of 25 samples each were examined: (1) sham exposure alone (control); (2)
      sham-exposure with TGF-beta1; (3) SMF exposure with TGF-beta1. The SMF or sham
      exposure was carried out for 10 days. Photomicrographs of tubular cells,
      immunostained with an anti-platelet-endothelial cell adhesion molecule-1 (PECAM-1
      [CD31]) antibody as a pan-endothelial marker, were analyzed after the 10-day
      culture. SMF was found to significantly reverse the inhibition of TGF-beta1 on
      tubular formation in terms of the area density and length of tubules
      (arteriogenesis) in the peripheral part of the wells, compared with the TGF-beta1
      treatment alone. These findings suggest that one of the possible exogenous
      factors for arteriogenesis might involve 'magnetic force' (the product of the
      magnetic flux density, the magnetic gradient, and the volume susceptibility of
      the cells) because values are much larger in the peripheral part than in the
      central part.

PMID- 17516507
TI  - Lack of promoting effects of chronic exposure to 1.95-GHz W-CDMA signals for IMT
      2000 cellular system on development of N-ethylnitrosourea-induced central nervous
      system tumors in F344 rats.
AB  - The present study was performed to evaluate effects of a 2-year exposure to an
      electromagnetic near-field (EMF) equivalent to that generated by cellular phones
      on tumor development in the central nervous system (CNS) of rats. For this
      purpose, pregnant F344 rats were given a single administration of N
      ethylnitrosourea (ENU) on gestational day 18. A total of 500 pups were divided
      into five groups, each composed of 50 males and 50 females: Group 1, untreated
      controls; Group 2, ENU alone; Groups 3 to 5, ENU + EMF (sham exposure and two
      exposure levels). A 1.95-GHz wide-band code division multiple access (W-CDMA)
      signal, which is a feature of the International Mobile Telecommunication 2000
      (IMT-2000) cellular system was employed for exposure of the rat head starting
      from 5 weeks of age, 90 min a day, 5 days a week, for 104 weeks. Brain average
      specific absorption rates (SARs) were designed to be .67 and 2.0 W/kg for low and
      high exposures, respectively. The incidence and numbers of brain tumors in female
      rats exposed to 1.95-GHz W-CDMA signals showed tendencies to increase but without
      statistical significance. Overall, no significant increase in incidences or
      numbers, either in the males or females, was detected in the EMF-exposed groups.
      In addition, no clear changes in tumor types in the brain were evident. Thus,
      under the present experimental conditions, exposure of heads of rats to 1.95-GHz
      W-CDMA signals for IMT-2000 for a 2-year period was not demonstrated to
      accelerate or otherwise affect ENU-initiated brain tumorigenesis.

PMID- 17516508
TI  - Effects of high frequency electromagnetic field (EMF) emitted by mobile phones on
      the human motor cortex.
AB  - We investigated whether the pulsed high frequency electromagnetic field (EMF)
      emitted by a mobile phone has short term effects on the human motor cortex. We
      measured motor evoked potentials (MEPs) elicited by single pulse transcranial
      magnetic stimulation (TMS), before and after mobile phone exposure (active and
      sham) in 10 normal volunteers. Three sites were stimulated (motor cortex (CTX),
      brainstem (BST) and spinal nerve (Sp)). The short interval intracortical
      inhibition (SICI) of the motor cortex reflecting GABAergic interneuronal function
      was also studied by paired pulse TMS method. MEPs to single pulse TMS were also
      recorded in two patients with multiple sclerosis showing temperature dependent
      neurological symptoms (hot bath effect). Neither MEPs to single pulse TMS nor the
      SICI was affected by 30 min of EMF exposure from mobile phones or sham exposure.
      In two MS patients, mobile phone exposure had no effect on any parameters of MEPs
      even though conduction block occurred at the corticospinal tracts after taking a
      bath. As far as available methods are concerned, we did not detect any short-term
      effects of 30 min mobile phone exposure on the human motor cortical output
      neurons or interneurons even though we can not exclude the possibility that we
      failed to detect some mild effects due to a small sample size in the present
      study. This is the first study of MEPs after electromagnetic exposure from a
      mobile phone in neurological patients.

PMID- 17516509
TI  - Pulsed electromagnetic fields affect osteoblast proliferation and differentiation
      in bone tissue engineering.
AB  - Bone tissue engineering is an interdisciplinary field involving both engineers
      and cell biologists, whose main purpose is to repair bone anatomical defects and
      maintain its functions. A novel system that integrates pulsed electromagnetic
      fields (PEMFs) and bioreactors was applied to bone tissue engineering for
      regulating osteoblast proliferation and differentiation in'vitro. Osteoblasts
      were acquired from the calvaria of newborn Wistar rats and isolated after
      sequential digestion. Poly(DL-lactic-co-glycolic acid) (PLGA) scaffolds were made
      by the solvent merging/particulate leaching method. Osteoblasts were seeded into
      porous PLGA scaffolds with 85% porosity and cultured in bioreactors for the 18
      day culture period. Cells were exposed to PEMF pulsed stimulation with average
      (rms) amplitudes of either 0.13, 0.24, or 0.32 mT amplitude. The resulting
      induced electric field waveform consisted of single, narrow 300 micros quasi
      rectangular pulses with a repetition rate of 7.5'Hz. The results showed that PEMF
      stimulation for 2 and 8 h at .13 mT increased the cell number on days 6 and 12,
      followed by a decrease on day 18 using 8 h stimulation. However, ALP activity was
      decreased and then increased on days 12 and 18, respectively. On the other hand,
      PEMF-treated groups (irrespective of the stimulation time) at 0.32 mT inhibited
      cell proliferation but enhanced ALP activity during the culture period. These
      findings suggested that PEMF stimulation with specific parameters had an effect
      on regulating the osteoblast proliferation and differentiation. This novel
      integrated system may have potential in bone tissue engineering.

PMID- 17516511
TI  - Increased expression and altered subunit composition of proteasomes induced by
      continuous proteasome inhibition establish apoptosis resistance and
      hyperproliferation of Burkitt lymphoma cells.
AB  - The proteasome is the main protease for extralysosomal protein degradation in
      eukaryotic cells, and constitutes a sophisticated high molecular mass proteinase
      complex underlying a tightly coordinated expression and assembly of multiple
      subunits and subcomplexes. Here we show that continuous inhibition of proteasomal
      chymotrypsin-like peptidase activity by the proteasome inhibitor bortezomib
      induces in human Namalwa Burkitt lymphoma cells increased de novo biogenesis of
      proteasomes accompanied by increased expression of the proteasome maturation
      protein POMP, increased expression of 19S-20S-19S proteasomes, and abrogation of
      expression of beta 1i, beta 2i and beta 5i immunosubunits and PA28 in favor of
      increased expression of constitutive proteolytic beta1, beta2 and beta 5 subunits
      and 19S regulatory complexes. These alterations of proteasome expression and
      subunit composition are accompanied by an increase in proteasomal caspase-like,
      trypsin-like and chymotrypsin-like peptidase activities, not inhibitable by high
      doses of bortezomib. Cells harboring these proteasomal alterations display rapid
      proliferation and cell cycle progression, and acquire resistance to apoptosis
      induced by proteasome inhibitors, gamma-irradiation and staurosporine. This
      acquired apoptosis resistance is accompanied by de novo expression of anti
      apoptotic Hsp27 protein and the loss of ability to accumulate and stabilize pro
      apoptotic p53 protein. Thus, increased expression, altered subunit composition
      and increased activity of proteasomes constitute a hitherto unknown adaptive and
      autoregulatory feedback mechanism to allow cells to survive the lethal challenge
      of proteasome inhibition and to establish a hyperproliferative and apoptosis
      resistant phenotype.

PMID- 17516513
TI  - Multiple roles of M-CSF in human osteoclastogenesis.
AB  - Although the critical role of M-CSF in osteoclastogenesis is well documented,
      there has been no detailed analysis of how it regulates human osteoclast
      formation and function in vitro. We used a human osteoclastogenesis model
      employing CFU-GM osteoclast precursors cultured for 14 days on dentine with
      RANKL, with varying exposure to exogenous human M-CSF. Short-term treatment of
      precursors with M-CSF (10-100 ng/mL) resulted in increased proliferation with or
      without RANKL. Treatment with M-CSF (1-100 ng/mL) for 14 days caused a biphasic
      concentration-dependent stimulation of formation, fusion, and resorption peaking
      at 10-50 ng/mL and almost complete abolition of resorption at 100 ng/mL. Time
      course studies using M-CSF (25 ng/mL) showed that osteoclast size, nuclei/cell,
      and resorption increased with longer duration of M-CSF treatment. When treatment
      was restricted to the first 4 days, M-CSF (25-100 ng/mL) stimulated formation of
      normal numbers of osteoclasts that resorbed less. Blockade of endogenous M-CSF
      signaling with neutralizing M-CSF antibody during the first week of culture
      extensively inhibited osteoclastogenesis, whereas blockade during the second week
      produced only a small reduction in resorption. Treatment with M-CSF during the
      second week of culture caused a small increase in osteoclast number and a
      concentration-dependent increase in cytoplasmic spreading with inhibition of
      resorption. We have shown that M-CSF modulates multiple steps of human
      osteoclastogenesis, including proliferation, differentiation and fusion of
      precursors. In the later stages of osteoclastogenesis, M-CSF modulates osteoclast
      resorbing activity, but is not required for survival. Modulation of M-CSF
      signaling is a potential therapeutic target for conditions associated with excess
      bone resorption.

PMID- 17516514
TI  - Mutation in G6PD gene leads to loss of cellular control of protein
      glutathionylation: mechanism and implication.
AB  - More than 400 million people are susceptible to oxidative stress due to glucose-6
      phosphate dehydrogenase (G6PD) deficiency. Protein glutathionylation is believed
      to be responsible for loss of protein function and/or cellular signaling during
      oxidative stress. To elucidate the implications of G6PD deficiency specifically
      in cellular control of protein glutathionylation, we used hydroxyethyldisulfide
      (HEDS), an oxidant which undergoes disulfide exchange with existing thiols. G6PD
      deficient (E89) cells treated with HEDS showed a significant increase in protein
      glutathionylation compared to wild-type (K1) cells. In order to determine whether
      increase in global protein glutathionylation by HEDS leads to loss of function of
      an important protein, we compared the effect of HEDS on global protein
      glutathionylation with that of Ku protein function, a multifunctional DNA repair
      protein, using a novel ELISA. E89 cells treated with HEDS showed a significant
      loss of Ku protein binding to DNA. Cellular protein thiol and GSH, whose
      disulfide is involved in protein glutathionylation, were decreased by HEDS in E89
      cells with no significant effect in K1 cells. E89 cells showed lower
      detoxification of HEDS, that is, conversion of disulfide HEDS to free sulfhydryl
      mercaptoethanol (ME), compared to K1 cells. K1 cells maintained their NADH level
      in the presence of HEDS but that of E89 cells decreased by tenfold following a
      similar exposure. NADPH, a cofactor required to maintain reduced form of the
      thiols, was decreased more in E89 than K1 cells. The specific role of G6PD in the
      control of such global protein glutathionylation and Ku function was further
      demonstrated by reintroducing the G6PD gene into E89 (A1A) cells, which showed a
      normal phenotype.

PMID- 17516515
TI  - Review: hepatitis B immune globulin for prevention of hepatitis B infection.
AB  - Specific hepatitis B immune globulin (HBIG) contains a high titer of antibody to
      hepatitis B surface antigens and provides immediate passive protection against
      infection with hepatitis B virus, after acute exposure to infection. It is now
      generally combined with active immunization with hepatitis B vaccine. The
      principal indications for administration of HBIG are: a single acute percutaneous
      exposure to hepatitis B virus (HBV); mucocutaneous exposure; unprotected sexual
      exposure; mother-to-infant transmission; prevention of re-infection after liver
      transplantation; non-responders to hepatitis B vaccine and immunosuppressed
      patients.

PMID- 17516516
TI  - Genetic and phenotypic diversity of echovirus 30 strains and pathogenesis of type
      1 diabetes.
AB  - Several enterovirus serotypes should be considered as potentially diabetogenic.
      The capacity of an enterovirus to kill or impair the functions of human beta
      cells can vary among the strains within a given serotype as shown previously for
      echovirus 9 and 30 (E-30). The evolution of E-30 has also shown patterns
      correlating with the global increase of type 1 diabetes incidence. In the present
      study, antigenic properties of a set of E-30 isolates were investigated and the
      results correlated with the previously documented beta-cell destructive phenotype
      of the strains, or to genetic clustering of the strains. No simple correlation
      between the three properties was observed. A full-length infectious clone was
      constructed and sequenced from one of the isolates found to be most destructive
      to beta-cells (E-30/14916net87). Phylogenetic analyses demonstrated that this
      strain was closely related to the E-30 prototype strain at the capsid coding
      region while outside the capsid region prototype strains of several other human
      enterovirus B serotypes clustered more closely. This suggests that the relatively
      greater pathogenicity of the strain might be based on properties of the genome
      outside of the structural protein coding region. Neutralizing antibody assays on
      sera from 100 type 1 diabetic patients and 100 controls using three different E
      30 strains did not reveal differences between the groups. This finding does not
      support a previous proposition of aberrant antibody responses to E-30 in diabetic
      patients. It is concluded that identification of the genetic counterparts of
      pathogenicity of E-30 strains requires further studies.

PMID- 17516517
TI  - Effective program against mother-to-child transmission of HIV at Saint Camille
      Medical Centre in Burkina Faso.
AB  - The present research was aimed to prevent mother-to-child transmission of HIV; to
      use RT-PCR in order to detect, 6 months after birth, infected children; and to
      test the antiretroviral resistance of both children and mothers in order to offer
      them a suitable therapy. At the Saint Camille Medical Centre, 3,127 pregnant
      women (aged 15-44 years) accepted to be enrolled in the mother-to-child
      transmission prevention protocol that envisages: (i) Voluntary Counselling and
      Testing for all the pregnant women; (ii) Antiretroviral therapy for HIV positive
      pregnant women and for their newborns; (iii) either powdered milk feeding or
      short breast-feeding and RT-PCR test for their children; (iv) finally, pol gene
      sequencing and antiretroviral resistance identifications among HIV positive
      mothers and children. Among the patients, 227/3,127 HIV seropositive women were
      found: 221/227 HIV-1, 4/227 HIV-2, and 2/227 mixed HIV infections. The RT-PCR
      test allowed the detection of 3/213 (1.4%) HIV infected children: 0/109 (0%) from
      mothers under ARV therapy and 3/104 (2.8%) from mothers treated with Nevirapine.
      All children had recombinant HIV-1 strain (CRF06_CPX) with: minor PR mutations
      (M36I, K20I) and RT mutations (R211K). Among them, two twins had Non-Nucleoside
      Reverse Transcriptase Inhibitor mutation (Y18CY). Both mothers acquired a major
      PR mutation (V8IV), investigated 6 months after a single-dose of Nevirapine.
      Prevention by single-dose of Nevirapine reduced significantly mother-to-child
      transmission of HIV, but caused many mutations and resistance to antiretroviral
      drugs. Based on present study the antiretroviral therapy protocol, together with
      the artificial-feeding, might represent the ideal strategy to avoid transmission
      of HIV from mother-to-child.

PMID- 17516519
TI  - Molecular characterization of hepatitis A virus isolates from Argentina.
AB  - Hepatitis A, a vaccine preventable disease, is now of transitional or
      intermediate endemicity in Argentina, as the epidemiologic pattern of the disease
      has shifted with improvements in living conditions in some parts of the country.
      Increase in the susceptibility of older children and adults has led to increasing
      disease incidence. Molecular epidemiology has played an important role in the
      understanding of HAV infection by identifying modes of spreading and by
      permitting the monitoring of changes in circulating virus brought about by
      prevention programs. South American isolates characterized are limited. Eighty
      two sporadic and outbreak isolates from Argentina were sequenced in the VP1/2A
      region of HAV genome over a 9-year period. All the isolates belonged to
      subgenotype IA. All our sequences grouped into two big clusters. Apparently, at
      least two lineages have been co-circulating in the same place at the same time.
      Despite great genetic variability, few point amino acid changes could be deduced.
      Four sequences showed an Arg --> Lys substitution at 1-297 which characterized
      the genotype IB at the amino acid level. Many isolates carried a conservative
      amino acid substitution Leu --> Ile at position 42 of the 2A domain, previously
      described as a possible fingerprint of HAV sequences in Brazil. The other rare
      changes have been found before, except for a 1-277 Asn --> Ser substitution
      displayed in two isolates that has not been previously reported. Argentina
      recently implemented universal vaccination in 1-year-old children. Molecular
      tools would be useful in an active surveillance program.

PMID- 17516520
TI  - Characteristics of lamivudine-resistant hepatitis B virus (HBV) strains with and
      without breakthrough hepatitis in patients with chronic hepatitis B evaluated by
      serial HBV full-genome sequences.
AB  - Lamivudine therapy often causes breakthrough of hepatitis B virus (HBV) DNA and
      breakthrough hepatitis. The aim of this study was to determine the viral factors
      that relate to HBV-DNA breakthrough with and without breakthrough hepatitis.
      Among 82 patients with chronic hepatitis B (CHB) who received lamivudine at a
      dose of 100 mg daily for more than 24 months, 23 patients had HBV-DNA
      breakthrough induced by a lamivudine-resistant mutant. Of these 23 patients, 16
      had breakthrough hepatitis and 7 had only HBV-DNA breakthrough. Serial HBV-DNA
      full-genome sequences during therapy were examined in 10 (7 had breakthrough
      hepatitis and 3 did not) of these 23 patients by direct sequencing. Mutations in
      the S region were examined by cloning in representative patients. There were no
      significant differences in the baseline clinical backgrounds and virus marker
      between patients with and without breakthrough hepatitis. The HBV amino acid
      substitutions at breakthrough hepatitis were identical to those at HBV-DNA
      breakthrough. Cloning analysis revealed that monoclonal mutational strain
      appeared at breakthrough and no such mutations existed at baseline. Regarding HBV
      amino acid substitutions in the polymerase region, S region, X region, and
      precore-core region with breakthrough compared to baseline, there was no
      significant differences of the numbers of amino acid substitution between
      breakthrough hepatitis and non-breakthrough hepatitis. There were no common amino
      acid changes in patients with breakthrough hepatitis. Although monoclonal
      lamivudine-resistant strain emerged at HBV-DNA breakthrough in patients with CHB,
      there were no common amino acid changes, suggesting viral factor may have
      insignificant role in breakthrough hepatitis.

PMID- 17516521
TI  - Seroepidemiology of hepatitis E virus in patients with non-A, non-B, non-C
      hepatitis in Hungary.
AB  - Many cases of acute hepatitis remain undiagnosed and the hepatitis E virus (HEV)
      is emerging in industrialized countries. The aim of this study was to assess the
      role HEV as causative agent in acute non-A, non-B, and non-C hepatitis patients
      in Hungary. 10.5% of the 264 acute non-A, non-B, and non-C hepatitis patients
      tested had anti-HEV IgG and 1.9% had anti-HEV IgM as tested by ELISA. After
      confirmation by Western blot 6.1% of the acute non-A, non-B, and non-C hepatitis
      patients had anti-HEV IgG antibodies only and 1.1% of the patients had both IgG
      and IgM. All 19 patients that were positive for anti-HEV IgG and/or IgM tested
      negative for HEV RNA by PCR. Only a small proportion of the acute hepatitis cases
      in the southwest of Hungary are assumed to be attributed to HEV infection,
      however, hepatitis E should be considered along with hepatitis A, B, and C in the
      diagnosis of acute hepatitis.

PMID- 17516522
TI  - Genotypes and molecular epidemiology of human astroviruses in hospitalized
      children with acute gastroenteritis in Rio de Janeiro, Brazil.
AB  - Human astrovirus (HAstV) is an important pathogen that causes acute
      gastroenteritis mainly in children up to 5 years old worldwide. A total of 318
      fecal samples were collected from January to December of 2004 from children with
      acute gastroenteritis hospitalized in Rio de Janeiro (RJ), Brazil. The samples
      were obtained from three public hospitals and were previously investigated for
      the presence of rotavirus (RV) and enteric adenovirus (AdV). The aim of this
      study was to determine the prevalence and molecular characterization of HAstV by
      reverse-transcription polymerase chain reaction (RT-PCR) and partial sequencing
      of open reading frame 2 (ORF2). HAstV infections were detected in 43 (14%) of the
      samples, of which 19 (6%) were mixed infections with HAstV and RV. HAstV were
      identified in all age groups, with 85% of the cases occurring in children younger
      than 2 years old. HAstV infections were more prevalent from March to May.
      Diarrhea, vomiting, and fever were the main clinical manifestations observed in
      these infections. Partial capsid sequencing of 35 HAstV strains characterized 25
      (71%) as genotype 1 (HAstV-1), 6 (17%) HAstV-2, 3 (9%) HAstV-8, and 1 (3%) HAstV
      4. Based on the genetic variability, three lineages were observed between RJ
      HAstV-1 strains. This study demonstrated the importance of HAstV infections
      causing acute infantile gastroenteritis in hospitalized children in RJ, Brazil.
      Molecular epidemiological surveillance is helpful for designing prevention
      strategies of HAstV transmission.

PMID- 17516523
TI  - Anti-HTLV-1 tax antibody and tax-specific cytotoxic T lymphocyte are associated
      with a reduction in HTLV-1 proviral load in asymptomatic carriers.
AB  - Previous studies have suggested that higher anti-human T-lymphotropic virus 1
      (HTLV-1) antibody titer and lower anti-HTLV-1 Tax antibody reactivity are risk
      factors for adult T-cell leukemia/lymphoma. In the present study, we analyzed the
      relationships between these factors and clarified their significance. Forty-five
      carriers were examined for anti-HTLV-1 and anti-Tax antibody by ELISA. In
      addition, 43 of the 45 carriers with HLA-A*0201 and/or A*2402 were examined for
      frequency of Tax-specific cytotoxic T lymphocytes (CTLs) using HTLV-1/HLA
      tetramers, and 44 were examined for proviral load by real-time PCR. The
      relationships between these factors were analyzed statistically. The frequencies
      of Tax11-19 and Tax301-309-specific CTLs were significantly higher in the anti
      Tax antibody-positive group as compared with the antibody-negative group (P =
      0.002 and 0.033, respectively). Anti-HTLV-1 antibody titer had a positive
      correlation with proviral load (P = 0.019), whereas anti-Tax antibody did not
      show a significant correlation. Higher frequencies of both Tax11-19 and Tax301
      309-specific CTLs are related to a reduction in proviral load (P = 0.017 and
      0.015, respectively). Synergistic interactions of humoral and cellular immunity
      against Tax protein were demonstrated in HTLV-1 carriers. Tax-specific CTL may
      reduce HTLV-1 proviral load to prevent asymptomatic carriers from developing
      adult T-cell leukemia/lymphoma.

PMID- 17516524
TI  - Group A rotavirus strains circulating in the eastern center of Tunisia during a
      ten-year period (1995-2004).
AB  - An epidemiological survey investigating rotavirus infections in children was
      undertaken in the Eastern Center of Tunisia between January 1995 and December
      2004. A total of 982 faecal specimens collected from children less than 5 years
      in age were screened by enzyme-linked immunosorbent assay (ELISA) or latex
      agglutination assay for the presence of group A rotavirus antigen. Rotavirus
      positive samples were used for G and P typing by multiplex semi-nested reverse
      transcription-PCR. Rotaviruses were detected in 22% (n = 220) of stools. Of
      these, 164 were typed for VP7: G genotypes found were G1 (59%), G2 (2%), G3 (9%),
      G4 (10%), G8 (1%), and G9 (1%). Sixteen specimens (9%) showed mixed G profiles. A
      total of 119 specimens were typed for VP4. P genotypes detected were P[8] (32%),
      P[6] (15%), and P[4] (13%). Mixed P profiles were also detected (6%). Although
      the distribution of the detected genotypes appeared to change annually, G1P[8]
      rotavirus strains always predominated during the 10-year period of study. This is
      the first report of rotaviruses in Tunisia with unconventional VP7 serotypes such
      as G8 and G9, highlighting the need for continual surveillance of emerging
      strains in Northern Africa. Indeed, the new commercial vaccines only contain the
      VP7 genes that dictate G1 or G1 to G4 specificities. These vaccines may protect
      less well against unusual strains circulating in countries planning to implement
      a rotavirus vaccine strategy.

PMID- 17516525
TI  - Sequence analysis of the VP7 gene of human rotavirus G1 isolated in Japan, China,
      Thailand, and Vietnam in the context of changing distribution of rotavirus G
      types.
AB  - Over the last decade, rotavirus G1 has represented the most common genotype
      worldwide. Since 2000, the prevalence of rotavirus G1 has decreased in some
      countries such as Japan and China. To monitor the trend of the VP7 encoding gene
      of rotavirus G1, we performed a sequence analysis of 74 G1 rotavirus strains
      isolated in Japan, China, Thailand, and Vietnam during the period from 2002 to
      2005. The phylogenetic tree showed that all of the studied G1 strains from the
      four countries clustered into lineage III, the same as the majority of the G1
      strains isolated in China and Japan in 1990 and 1991. Examination of the deduced
      amino acid sequences of the G1 strains from China and Japan revealed an amino
      acid substitution at position 91 (Asn instead of Thr) in antigenic region A when
      compared to the G1 strains isolated in China and Japan in 1990, 1991, and global
      reference strains. For the G1 strains from Thailand and Vietnam, there were three
      amino acid substitutions, not belonging to any antigenic regions. The study
      showed that there have been no considerable changes of human rotavirus G1
      isolated in Japan, China, Thailand, and Vietnam. Further studies need to be
      carried out for a better understanding of why such changes in the prevalence of
      rotavirus G1 occur in these countries.

PMID- 17516526
TI  - Application of molecular and serological assays to case based investigations of
      rubella and congenital rubella syndrome.
AB  - Rubella and congenital rubella syndrome continue to be important health problems
      worldwide. The detection of rubella RNA directly in clinical specimens is a
      critical factor in early laboratory diagnosis of recent or congenital infection,
      in addition to detection of rubella-specific IgM. In order to comply with recent
      WHO recommendations for establishing uniform genetic analysis protocols for
      rubella virus we have developed a new block based PCR assay (PCR-E317), which
      extends the sequence generated by the block based PCR-E592 currently in use, to
      cover the minimum acceptable 739 nucleotides (nt) window at the E1 gene. In
      addition, a real-time PCR assay has been developed to allow rapid detection of
      the virus in the laboratory. The assays were applied to a number of clinical
      specimens collected from patients including recent rubella incidences in the UK,
      Ethiopia and Turkey, two prenatal and two congenital rubella syndrome cases.
      Rubella RNA was detected in specimens from two patients that were collected too
      early for IgM detection, in two amniotic fluids for prenatal diagnosis and in the
      follow up specimens from the two infant with congenital rubella syndrome tested
      for viral secretion. At least four genotypes were identified among these
      patients. The results showed that molecular assays are important tools in the
      early diagnosis of rubella and congenital rubella syndrome, in the provision of
      molecular epidemiological information for tracking transmission pathways and in
      adding to the knowledge of rubella strain distribution worldwide.

PMID- 17516527
TI  - Genotyping of recent measles virus strains from Russia and Vietnam by nucleotide
      specific multiplex PCR.
AB  - The nucleoprotein genes of 49 measles virus (MV) strains circulating in Russia
      between 2000 and 2006 and in Vietnam in 2003 were analyzed by genotype-specific
      PCR and the results were compared with their sequences. The sequences revealed
      the presence of genotypes H1 and H2 in the center (Nha Trang) and the north
      (Hanoi) of Vietnam, respectively. The relative diversity of the H2 strains
      suggested an endemic circulation of these viruses in the capital. In contrast
      genotype H1 strains from Nha Trang were homogenous genetically, which may
      indicate a recent importation. The strains obtained from 12 different regions of
      the Russian Federation were assigned to the genotypes H1, D4, and D6. Most
      strains (81.4%) were correctly genotyped by a multiplex PCR method which was
      sensitive to genotype-specific mutations [Kremer et al. (2004): J Clin Microbiol
      42: 3017-3022]. Ambiguous or negative results for some clade H and genotype D6
      strains were due to point mutations in the type-specific primer binding sites.
      After exchanging a single nucleotide in both the clade H- and the genotype D6
      specific primers, all strains were assigned correctly to their genotype. A
      simplified procedure for use in Vietnam was developed to distinguish directly
      between genotypes H1 and H2 and any non-H genotype. These results demonstrate
      that our multiplex PCR method can be adapted easily to new sequence variants or
      specific epidemiological situations, and thus be very useful for rapid genotyping
      of large number of samples even in laboratories which do not have sequencing
      facilities.

PMID- 17516528
TI  - Molecular epidemiology of acute hepatitis B in the Netherlands in 2004:
      nationwide survey.
AB  - To gain insight into hepatitis B virus (HBV) transmission in the Netherlands,
      epidemiological data and sera were collected from reported cases of acute HBV
      infections in the Netherlands in 2004. Cases were classified according to mode of
      transmission. A fragment of the S-gene of HBV (648 bp) was amplified, sequenced,
      and subjected to phylogenetic analysis. Of the 291 acute HBV cases reported in
      2004, 158 (54%) were available for genotyping. Phylogenetic analysis identified 6
      genotypes: A (64%), B (3%), C (3%), D (21%), E (5%) and F (5%). Of HBV infected
      men having sex with men, 86% were infected with genotype A, accounting for 43% of
      all patients infected with this genotype. There were only three reported cases of
      injecting drug use of which one was available for sequencing (genotype A). Unlike
      the genotype A cluster, sequences within the genotype B-E clusters were
      heterogenic. Within genotype F, several isolates had identical sequences, but
      patients could not be epidemiologically linked. Sexual transmission, particularly
      by men having sex with men was the most important transmission route for HBV.
      Injecting drug use plays a minor role. Genotype A is predominant in the
      Netherlands, especially among men having sex with men. In addition to imported
      strains, there seems to be a pool of related but non-identical strains
      circulating among chronic carriers in the migrant population, from which
      occasionally new patients are infected, primarily by heterosexual transmission.

PMID- 17516529
TI  - Epidemiologic aspects and laboratory features of enterovirus infections in
      Western Germany, 2000-2005.
AB  - From 2000 to 2005, a total of 1,096 enterovirus infections were diagnosed either
      by isolation of virus from cell culture or by RT-PCR (5'non-coding region (NCR)).
      Typing of viruses (n = 674) was carried out by immunofluorescence with monoclonal
      antibodies, neutralization test or molecular methods. Seasons with high
      enterovirus activity were characterized by high prevalence of echovirus 30 (62.2%
      in 2000, 25.5% in 2001) and echovirus 13 (34.5% in 2001). In contrast, in the
      2003 season, which had very low enterovirus activity, these types were rare.
      During this season, cell culture sensitivity (human colonic carcinoma cells and
      human embryonic lung fibroblasts (HEL)) was exceptionally low. In order to
      determine the type of "non-cultivable" enteroviruses, purified RNA from selected
      stool samples was subjected to direct molecular typing. VP1/2A-specific fragments
      were amplified by RT-PCR, cloned and sequenced. The predominant virus identified
      was coxsackie A. Consequently, rhabdomyosarcom cells were introduced into the
      daily routine, which improved the isolation of enteroviruses. Echovirus 30 was
      again most commonly isolated during seasons 2004 and 2005 with increasing
      enterovirus activity. In conclusion, high prevalence of echovirus 30 and 13 is
      indicative of seasons with high enterovirus activity. The type of circulating
      enteroviruses may influence isolation of enterovirus from cell culture. RT-PCR
      (VP1/2A) combined with cloning and sequencing of amplicons is a useful tool for
      viral typing directly from stool samples. In cases of severe enterovirus
      infection, virological diagnosis should not solely rely on virus isolation from
      cell culture.

PMID- 17516530
TI  - Association between HLA-DRB1 polymorphism, high-risk HPV infection and cervical
      neoplasia in southern Chinese.
AB  - Multiple determinants are involved in the progression of human papillomavirus
      (HPV)-infected cervical lesion to invasive cancer. Human leukocyte antigen (HLA)
      polymorphism seems to play a role. This study examined the association between
      HLA-DRB1 polymorphism, high-risk HPV infection, and the development of cervical
      neoplasia in southern Chinese. Three hundred and seventy women with cervical
      neoplasia (43 cervical intraepithelial neoplasia grade II, 154 grade III, and 173
      invasive cancers) and 323 controls were recruited for HLA-DRB1 typing by a
      sequence-based approach. Cervical specimens were collected for HPV detection by a
      consensus primer-based polymerase chain reaction, and with the type of HPV
      identified by hybridization with type-specific oligonucleotide probes. A
      protective effect of HLA-DRB1*12 for cervical neoplasia was observed, and with
      stronger associations when subgroup analyses were carried out for patients
      infected with HPV16 and HPV58. The protective effect of HLA-DRB1*13 that had been
      reported from other populations was not observed. The data obtained in this study
      showed that HLA-DRB1*03 conferred a higher risk for HPV18-infected, but not for
      HPV16-, HPV52-, or HPV58-infected cervical lesions. Although, HPV52 was reported
      as uncommon worldwide, it was found to be the second most prevalent type in the
      southern Chinese population. However, no additional risk association was observed
      when subgroup analyses were performed for HPV52-infected patients. The current
      study shows that, among southern Chinese, the outcome of HPV-infected cervical
      lesions is associated with HLA-DRB1 polymorphism. These associations often vary
      with the type of HPV infection.

PMID- 17516531
TI  - Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1
      infected Kenyan children with treatment failure.
AB  - Recently increased availability of anti-retroviral therapy (ART) has mitigated
      HIV-1/AIDS prognoses especially in resource poor settings. The emergence of ART
      resistance-associated mutations from non-suppressive ART has been implicated as a
      major cause of ART failure. Reverse transcriptase inhibitor (RTI)-resistance
      mutations among 12 non-subtype B HIV-1-infected children with treatment failure
      were evaluated by genotypically analyzing HIV-1 strains isolated from plasma
      obtained between 2001 and 2004. A region of pol-RT gene was amplified and at
      least five clones per sample were analyzed. Phylogenetic analysis revealed HIV-1
      subtype A1 (n = 7), subtype C (n = 1), subtype D (n = 3), and CRF02_AG (n = 1).
      Before treatment, 4 of 12 (33.3%) children had primary RTI-resistance mutations,
      K103N (n = 3, ages 5-7 years) and Y181C (n = 1, age 1 year). In one child, K103N
      was found as a minor population (1/5 clones) before treatment and became major
      (7/7 clones) 8 months after RTI treatment. In 7 of 12 children, M184V appeared
      with one thymidine-analogue-associated mutation (TAM) as the first mutation,
      while the remaining 5 children had only TAMs appearing either individually (n =
      2), or as TAMs 1 (M41L, L210W, and T215Y) and 2 (D67N, K70R, and K219Q/E/R)
      appearing together (n = 3). These results suggest that "vertically transmitted"
      primary RTI-resistance mutations, K103N and Y181C, can persist over the years
      even in the absence of drug pressure and impact RTI treatment negatively, and
      that appearing patterns of RTI-resistance mutations among non-subtype B HIV-1
      infected children could possibly be different from those reported in subtype B
      infected children.

PMID- 17516532
TI  - Cellular HIV-1 DNA quantitation in patients during simplification therapy with
      protease inhibitor-sparing regimens.
AB  - Simplified regimens containing protease-inhibitors (PI)-sparing combinations were
      used in patients with virological suppression after prolonged highly active
      antiretroviral therapy. This study evaluated the total HIV-1 DNA quantitation as
      a predictor of long-term success for PI-sparing simplified therapy. Sixty-two
      patients were enrolled in a prospective non-randomized cohort. All patients have
      been receiving a triple-therapy regimen, two nucleoside reverse transcriptase
      inhibitors (NRTIs) plus one PI, for at least 9 months and were characterized by
      undetectable plasma HIV-1 RNA levels (<50 cp/ml) for at least 6 months. Patients
      were changed to a simplified PI-sparing regimen to overcome PI-associated adverse
      effects. HIV-DNA levels in peripheral blood mononuclear cells (PBMCs) were
      evaluated at baseline and at the end of follow-up. Patients with proviral DNA
      levels below the median value (226 copies/10(6) PBMCs) had a significant higher
      CD4 cell count at nadir (P = 0.003) and at enrolment (P = 0.001) with respect to
      patients with HIV-DNA levels above the median value. At month 18, 53 out of 62
      (85%) patients on simplified regimen showed virological success, 4 (6.4%)
      patients experienced virological failure and 5 (8%) patients showed viral blip.
      At logistic regression analysis, HIV-DNA levels below 226 copies/10(6) PBMCs at
      baseline were associated independently to a reduced risk of virological failure
      or viral blip during simplified therapy (OR 0.002, 95% CI 0.001-0.46, P = 0.025).
      The substitution of PI with NRTI or non-NRTIs may represent an effective
      treatment option. Indeed, treatment failure or viral blip were experienced by 6%
      and 8% of the patients on simplified therapy, respectively. In addition,
      sustained suppression of the plasma viral load was significantly correlated with
      low levels of proviral DNA before treatment simplification.

PMID- 17516533
TI  - Evolution of viral load and changes of polymerase and precore/core promoter
      sequences in lamivudine-resistant hepatitis B virus during adefovir therapy.
AB  - Adefovir dipivoxil (ADV) has demonstrated clinical activity against both wild
      type and lamivudine-resistant hepatitis B virus (HBV). We analyzed the evolution
      of viral load and the changes of polymerase and precore/core promoter sequences
      in lamivudine-resistant virus during ADV therapy. The authors studied 14 patients
      who had breakthrough hepatitis after lamivudine therapy. Serial sera were
      obtained prior to adefovir administration and at 3, 6 and 12 months after ADV
      therapy. Nucleotide sequences of polymerase and the precore/core promoter from
      the hepatitis B virus were analyzed. The median serum HBV DNA decrease with
      adefovir treatment was 4.35 log(10) copies/mL at 12 months. Tyrosine-methionine
      aspartate-aspartate (YMDD) mutants were found in 12 patients among the 14
      patients with lamivudine resistance. The YMDD mutant viruses reversed to the wild
      type in 6 patients out of the 12 patients after 3-6 months of ADV after
      discontinuing lamivudine therapy. In the analysis of the nucleotide sequences of
      the precore/core promoter gene, core promoter mutants in 12 patients were
      replaced by wild-type virus in three patients (25%), while precore mutants in
      four patients were replaced by the wild-type in three patients (75%). The results
      demonstrate the patterns of polymerase and precore/core promoter mutations in
      lamivudine-resistant hepatitis B viruses and the reversion from the mutant to the
      wild-type in some patients. In addition, despite several mutations in the
      polymerase during ADV therapy, ADV effectively suppressed HBV replication without
      the emergence of resistant viral mutants.

PMID- 17516534
TI  - Molecular evidence of father-to-child transmission of hepatitis B virus.
AB  - At present in Japan, only high-risk infants born to chronic hepatitis B virus
      (HBV)-infected mothers are given HBV vaccine. However, children can contract the
      virus from other HBV-infected family members, including fathers. The aim of this
      study is to present substantial and unequivocal evidence of father-to-child
      transmission of HBV infection using techniques including homology analysis and
      phylogenetic analysis. Thirteen chronic HBV-infected members of five families
      that included eight children and their respective fathers were enrolled in this
      study. Homology analysis and phylogenetic analyses of 2 coding region, the S gene
      and X gene, from the HBV genome were performed comparing the 13 nucleotide
      sequences from the 13 subjects. The nucleotide homology among the five sets of
      fathers and children was quite high (99.3-100%). A phylogenetic tree constructed
      on the 13 nucleotide sequences showed that all 5 sets of fathers and children
      were grouped into the same cluster with high bootstrap values. These results
      strongly indicate that father-to-child transmission is an important route of HBV
      infection in Japan and it is recommend that universal vaccination against HBV
      infection be instituted immediately in Japan for all children, in accordance with
      the WHO recommendation of 1997.

PMID- 17516535
TI  - Human herpesvirus 6-associated retrobulbar optic neuritis in an HIV-infected
      patient: response to anti-herpesvirus therapy and long-term outcome.
AB  - Like other herpesviruses, human herpesvirus 6 (HHV-6) can reactivate in
      immunocompromised patients. A case is described of an HIV-1-infected patient who
      developed bilateral retrobulbar optic neuritis associated with HHV-6 infection. A
      59-year-old woman, infected with HIV for 18 years, interrupted antiretroviral
      treatment because of therapeutic failure and severe metabolic complications. She
      presented subsequently with blurred vision and ophthalmological examination
      showed visual loss due to optic neuritis. Her CD4+ count was 285 cells/mm(3) and
      her plasma HIV-1 RNA level was 5.5 log(10) copies (cp)/ml. Magnetic resonance
      imaging of the brain was normal. HHV-6 loads were 3.2 log cp/ml in cerebrospinal
      fluid (CSF) and 6.3 log cp/10(6) peripheral blood mononuclear cells. Combined
      intravenous treatment was started with foscarnet and ganciclovir then changed to
      cidofovir and long-term valganciclovir. Her ocular condition improved gradually
      despite little decrease of the HHV-6 load in the CSF. Salvage antiretroviral
      treatment was then administered, with marked immunological and virological
      responses, contributing to further progressive ocular improvement. HHV-6-related
      optic neuritis has not been described previously in HIV-infected patients. Anti
      HHV-6 treatment improved the patient's vision, but immune restoration seems to
      remain essential for long-term recovery.

PMID- 17516536
TI  - EBNA1 expression in a lung transplant recipient with hypocomplementemic
      urticarial vasculitis syndrome.
AB  - This article describes a transplant recipient with underlying hypocomplementemic
      urticarial vasculitis syndrome who expressed persistently Epstein-Barr virus
      nuclear antigen 1 (EBNA1) in peripheral blood. The patient received a bilateral
      lung transplant and was subsequently followed with monitoring of EBV expression
      in peripheral blood. Evaluation of viral expression in peripheral blood, serum,
      and graft tissue was performed with RT-PCR, Q-PCR, indirect immunofluorescence,
      anti-peptide assays, and in situ hybridization; samples were collected at various
      time-points up to 91 days post-transplantation. The patient expressed EBNA1 in
      8/10 (80%) of the peripheral blood samples tested during the post-transplantation
      period, and interestingly, even including the day of transplantation. After
      analyses of indicative EBV mRNA, EBNA1 expression was found mainly to be Qp
      initiated EBNA1, known to be important for EBV maintenance. Anti-EBNA1 epitope
      mapping showed significantly higher and broader antibody responses to EBNA1
      epitopes pre-transplantation when compared to normal controls and a matched lung
      transplant control. Post-transplantation this response was largely diminished but
      there were still epitopes significantly higher than controls. Our results show
      the presence of EBV-positive proliferating cells before onset of intensive
      immunosuppressive treatment. Although no previous connection between EBV and
      hypocomplementemic urticarial vasculitis syndrome has been reported, it is
      tempting to speculate that the continuous EBNA1 expression is not caused by
      immunosuppression or post-transplant lymphoproliferative disease, but may be a
      factor involved in the etiology of the autoimmune disease.

PMID- 17516537
TI  - Different genotype pattern of varicella-zoster virus obtained from patients with
      varicella and zoster in Germany.
AB  - The general use of the varicella vaccine requires the surveillance of varicella
      zoster virus (VZV) strains in patients infected with VZV. This paper reports the
      data achieved from a prospective study of genotyping VZV in Germany, analyzing
      the restriction fragment length polymorphism (RFLP) of the open reading frames
      (ORF) 38, 54, and 62 as well as the polymorphism of the R5 repeat region. The
      study included 177 patients with varicella. Seventy-eight patients with zoster
      served as controls. Results revealed that 78% of VZV strains in patients with
      varicella had the genetic profile of the dominant wild-genotype occurring in
      Europe and 22% had the markers of African or Asian strains. Varicella patients
      with the profile of African or Asian strains were significantly younger than
      patients with varicella caused by the dominant genotype. By contrast, all zoster
      patients exhibited strains representing the majority of wild-type strains in
      Europe. In conclusion, VZV strains from patients with varicella have a
      significantly higher genetic variability than viral strains from zoster patients.
      Since variants with the markers of African or Asian strains could only be found
      in young children with chickenpox, the results suggest a changing scene of VZV
      genotypes in Germany. As reasons, the spread of viruses, which may be imported
      originally by persons immigrating from warmer climates, or the recombination
      between wild-and vaccine-type viruses have to be considered.

PMID- 17516538
TI  - Brazilian P[8],G1, P[8],G5, P[8],G9, and P[4],G2 rotavirus strains: nucleotide
      sequence and phylogenetic analysis.
AB  - Rotavirus epidemiological surveys with molecular analysis of strains are required
      for gastroenteritis control and prevention. Twenty-nine human rotavirus strains
      detected in Rio de Janeiro, Brazil, from 1986 to 2004 were characterized as
      P[8],G1, P[8],G5, P[8],G9, and P[4],G2 genotypes. The VP7 genes were sequenced
      and phylogenetic analysis was performed. Strains of genotype G1 revealed two
      distinct lineages, G1-3 and G1-4; strains of genotype G2 grouped in lineage G2-1;
      G5 strains clustered with other Brazilians G5 strains and G9 strains were closely
      related to each other in lineage G9-3, distinct from the original G9 strains
      detected in 1980s. The VP4 genes were analyzed and P[8] strains fell into two
      major genetic lineages, P[8]-2 and P[8]-3. Our findings document an intragenotype
      diversity represented by lineages and sublineages within rotavirus circulating in
      Rio de Janeiro from 1986 to 2004, before application of a vaccine (Rotarix) in
      Brazil. This report emphasizes the importance of continuing monitor genotypes to
      verify if uncommon strains or newly strains are emerging to be specifically
      addressed in future vaccine trials.

PMID- 17516539
TI  - Does serum alpha interferon measurement aid in the etiological diagnosis of
      febrile adult patients?
AB  - In febrile patients, distinguishing bacterial from viral infections is crucial
      for early treatment initiation and rational use of antibiotics. Raised interferon
      alpha (IFN-alpha) levels in serum has been associated with a wide range of viral
      infections. We evaluated the effectiveness of IFN-alpha serum measurements for
      the etiological diagnosis of febrile patients. Adult patients who were attending
      the emergency department with body temperature above or equal to 38.5 degrees C
      were studied prospectively, followed-up until day 30, and classified by two
      independent experts (blind for IFN-alpha results) as having a bacterial/parasitic
      infection, viral infection, or other diagnosis. The results of IFN-alpha
      measurements in blood samples taken in the emergency room, were compared with
      expert diagnosis. Among 243 patients included, 167 had bacterial/parasitic
      infections (including 19 with viral co-infection), 59 had viral infections, and
      36 other diagnoses. IFN-alpha assay had a sensitivity of 0.44 and a specificity
      of 0.92 for the diagnosis of viral infection. Among the 20 patients with acute
      viral infection according to the emergency physician diagnosis, 7 (35%) were
      given antibiotics, including four patients with raised IFN-alpha concentrations.
      It is concluded that in febrile patients, raised serum IFN-alpha level is highly
      specific of the viral etiology of fever but poorly sensitive. Reliable viral and
      bacterial biological markers are needed in order to improve rational use of
      antibiotics.

PMID- 17516540
TI  - Patch-clamp 'mapping' of ion channel activity in human sperm reveals
      regionalisation and co-localisation into mixed clusters.
AB  - Ion channels are pivotal to many aspects of sperm physiology and function. We
      have used the patch clamp technique to investigate the distribution of ion
      channels in the plasma membrane of the head of human spermatozoa. We report that
      three types of activity are common in the equatorial and acrosomal regions of the
      sperm head. Two of these (a chloride-permeable anion channel showing long stable
      openings and a second channel which flickered between open and closed states and
      was dependent upon cytoplasmic factors for activity) were localised primarily to
      the equatorial segment. A third type, closely resembling the flickering activity
      but with different voltage sensitivity of P(open), was more widely distributed
      but was not detectable over the anterior acrosome. In the anterior acrosomal area
      channels were present but showed very low levels of spontaneous activity. A
      unique feature of channel activity in the sperm equatorial region was co
      localisation into mixed clusters, most patches were devoid of activity but
      'active' patches typically contained two or more types of activity (in a single
      200-300 nM diameter patch). We conclude that ion channels in the sperm membrane
      show regionalisation of type and activity and that the channels are clustered
      into functional groups, possibly interacting through local effects on membrane
      potential.

PMID- 17516541
TI  - Mitochondrial association of myocilin, product of a glaucoma gene, in human
      trabecular meshwork cells.
AB  - The trabecular meshwork (TM), an ocular tissue next to the cornea, is a major
      site for regulation of the aqueous humor outflow. Malfunctioning of this tissue
      is believed to be responsible for development of glaucoma, a major blinding
      disease. Myocilin is a gene directly linked to the most common form of glaucoma.
      Its protein product has been localized to both intra- and extra-cellular sites in
      TM cells. This study was to investigate the association of myocilin with
      mitochondria in TM cells. In vitro mitochondrial import assays showed that
      myocilin was imported to the TM mitochondria, targeting to mitochondrial
      membranes and/or the intermembrane space. The targeting was mediated mostly via
      the amino-terminal region of myocilin. When myocilin expression was induced
      either by treatment with dexamethasone or transfection with a myocilin construct,
      the mitochondrial membrane potential in TM cells, as assessed by JC-1 staining,
      was lowered. Subcellular fractionation and Western blot analyses confirmed that a
      portion of myocilin sedimented with the mitochondrial fractions. Upon anti-Fas
      treatment to provoke apoptosis, an increase of myocilin distribution in cytosolic
      fraction was observed, suggesting that myocilin was partially released from
      mitochondrial compartments. These results confirmed the association of myocilin
      with TM cell mitochondria and indicated that myocilin may have a proapoptotic
      role in TM cells.

PMID- 17516542
TI  - Adenosine A1 and A2A receptor effects on G-protein cycling in beta-adrenergic
      stimulated ventricular membranes.
AB  - In the heart beta1-adrenergic (beta1R) and adenosine A1 (A1R) and A2A (A2AR)
      receptors modulate contractile and metabolic function. The interaction between
      these receptors was investigated at the level of G-protein cycling by determining
      the effect of receptor agonists on the binding of GTP to G-proteins and
      displacement of G alpha-subunit-bound GDP by GTP. Crude membranes from rat heart
      or brain were stimulated by agonists for beta1R (isoproterenol; ISO), A1R
      (chlorocyclopentyladenosine, CCPA) and A2AR (CGS-21680; CGS). GTP binding to
      membranes was increased by ISO (17%), CCPA (6%) and CGS (12%). Binding values
      observed with incubation using ISO and CCPA together were significantly less than
      values obtained by the incubation of individual agents alone. With ISO, GTP
      binding to G alpha(s) subunits as determined by immunoprecipitation was increased
      79% in heart and 87% in brain. These increases were attenuated by CCPA, an effect
      that was inhibited by CGS. GDP release by membranes was increased 6.9% and 4.6%
      by ISO and CCPA, respectively. After co-incubation of these agonists, release was
      increased less than determined by the addition of the individual agent responses.
      CGS inhibited the reduced release caused by of CCPA. Adenylyl cyclase activity
      stimulated by ISO was attenuated 33% by CCPA, an effect inhibited by CGS.
      Together, these results indicate that A1R exert an antiadrenergic action at the
      level of beta1R stimulated G(s)-protein cycling and that A2AR reduce this action.

PMID- 17516543
TI  - Sprouty2 downregulation plays a pivotal role in mediating crosstalk between TGF
      beta1 signaling and EGF as well as FGF receptor tyrosine kinase-ERK pathways in
      mesenchymal cells.
AB  - Mammalian Sprouty2 (Spry2) is a key regulator of the receptor tyrosine kinase/ERK
      signaling pathway and is involved in many biological processes, including cell
      growth, differentiation, migration, and embryonic lung branching morphogenesis.
      Previous studies have shown that Spry2 expression is upregulated by many
      mitogens, particularly epidermal growth factor (EGF) and fibroblast growth
      factors (FGFs). In contrast, we report that transforming growth factor-beta1 (TGF
      beta1), which stimulates the growth of quiescent Swiss 3T3 cells, induced a dose
      dependent decrease of mouse Spry2 protein level within 24-h of treatment, and
      this effect was mediated by a MAP kinase-independent pathway. A concomitant
      reduction of the level of Spry2 mRNA indicates the involvement of a
      transcriptional mechanism, which requires histone deacetylase (HDAC) activity and
      de novo protein synthesis. On the other hand, the turnover rate of Spry2 protein
      was increased by TGF-beta1 treatment, suggesting enhanced Spry2 degradation.
      Treatment with lysosomal inhibitors, but not proteasome inhibitors, prevented the
      degradation of Spry2, thus, indicating that the degradation of Spry2 is mediated
      through the lysosomal pathway in Swiss 3T3 cells. Furthermore, we demonstrate
      that TGF-beta1 signaling can modulate EGF and FGF-induced ERK-MAP kinase
      activation by controlling Spry2 expression and function. Moreover, rescue of the
      TGF-beta1-induced downregulation of Spry2 by gene over-expression led to
      inhibition of the mitogenic effect of TGF-beta1 in Swiss 3T3 cells. Together, the
      combined operation of transcriptional and post-translational mechanisms suggests
      that regulation of Spry2 is a crucial event and emphasizes the important role
      that Spry2 plays in controlling cell behaviors.

PMID- 17516544
TI  - Dexamethasone promotes osteoclastogenesis by inhibiting osteoprotegerin through
      multiple levels.
AB  - Increased bone fragility attributed to osteopenia is a serious side effect of
      glucocorticoid treatment. Glucocorticoid-induced bone loss is caused primarily by
      hypofunction and apoptosis of osteoblasts, and secondarily by accelerated bone
      resorption. To explore the mechanism whereby dexamethasone (Dex) stimulates
      osteoclastogenesis in the coculture system, we analyzed the effect of Dex on the
      expression of both mouse osteoprotegerin (OPG) and receptor activator of NF
      kappaB ligand (RANKL). Dex reduced OPG transcripts and OPG protein secretion by
      the ST2 osteoblastic cells. Since mainly the c-Jun homodimer maintains the steady
      state transcription of the OPG gene, we examined the effect of Dex on c-Jun
      signaling in ST2 cells. Western blotting disclosed that Dex decreased the amount
      of phospho-c-Jun protein (p-c-Jun) and, correspondingly, the amount of the
      phosphorylated p46 isoform of Jun N-terminal kinase (JNK). The amount of phospho
      SEK1 also decreased after Dex treatment, while the amounts of phospho-ERK and p38
      remained constant. Among mitogen-activated protein (MAP) kinase inhibitors, the
      JNK inhibitor mimicked the inhibitory effect of Dex on OPG promoter activity. On
      the other hand, Dex treatment per se showed a nominal increase of RANKL gene
      expression. A part of Dex-mediated OPG gene suppression was achieved by the
      suppression of beta-catenin signaling. We speculate therefore that the bone
      resorptive action of Dex is mediated mainly by the inhibition of OPG by
      transrepressing the OPG gene through the AP-1 site, with a reduction (mediated
      mainly by the decrease in the p46 isoform of JNK) in the proportion of p-c-Jun in
      a JNK-dependent manner.

PMID- 17516545
TI  - Central role of interferon regulatory factor-1 (IRF-1) in controlling retinoic
      acid inducible gene-I (RIG-I) expression.
AB  - Retinoic acid inducible gene-I (RIG-I) functions as the first line of defense
      against viral infection by sensing dsRNA and inducing type I interferon (IFN)
      production. The expression of RIG-I itself is induced by IFN-alpha/beta and
      dsRNA. To comprehend the molecular mechanism of expression regulation, we cloned
      the RIG-I promoter and analyzed its activity upon IFN-beta and dsRNA treatment.
      Under basal condition, RIG-I mRNA level and promoter activity were significantly
      higher in normal cells versus their tumor counterparts. In both normal and cancer
      cells, RIG-I expression was induced by IFN-beta and dsRNA. A single IRF-1 binding
      site in the proximal promoter functioned as a crucial regulator of basal, IFN
      beta- and dsRNA-mediated induction of the RIG-I promoter. IFN-beta and dsRNA
      treatment increased IRF-1 binding to the RIG-I promoter. IRF-1 expression was
      also higher in normal cells than in cancer cells and it was induced by IFN-beta
      with similar kinetics as RIG-I. These results confirm that by controlling RIG-I
      expression, IRF-1 plays an essential role in anti-viral immunity. IRF-1 is a
      tumor suppressor and the expression profile of RIG-I together with its regulation
      by IRF-1 and the presence of a caspase-recruitment domain in RIG-I suggest that
      RIG-I might also possess tumor suppressor properties.

PMID- 17516546
TI  - Adjuvant radiation therapy is associated with improved survival for gallbladder
      carcinoma with regional metastatic disease.
AB  - BACKGROUND: Gallbladder carcinoma is a rare malignancy and is associated with
      dismal outcomes. The aim of this study was to better define the role of adjuvant
      radiation therapy in the management of gallbladder carcinoma. METHODS: The
      Surveillance, Epidemiological, and End Results (SEER) survey from the National
      Cancer Institute was queried from 1992 to 2002. Retrospective analysis was done.
      The end-point of the study was overall survival. RESULTS: There were a total of
      3,187 cases of gallbladder carcinoma in the registry from 1992 to 2002. Of the
      surgical group, 35% were stage I, 36% were stage II, 6% were stage III, and 21%
      were stage IV. Adjuvant radiation was used in 17% of the cases. The median
      survival for those patients receiving adjuvant radiation therapy was 14 months
      compared to an 8 months median survival for those treated without adjuvant
      radiation therapy (P < or = 0.001). The survival benefit associated with
      radiation use was only presenting those patients with regional spread (P =
      0.0001) and tumors infiltrating the liver (P = 0.011). CONCLUSION: The use of
      adjuvant radiation therapy is associated with improved survival in patients with
      locally advanced gallbladder cancer or gallbladder cancer with regional disease.

PMID- 17516547
TI  - Cilostazol attenuates MCP-1 and MMP-9 expression in vivo in LPS-administrated
      balloon-injured rabbit aorta and in vitro in LPS-treated monocytic THP-1 cells.
AB  - Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9)
      are involved in vascular inflammation. We tested the hypothesis, and explored the
      underlining mechanisms that cilostazol, a phosphodiesterase 3 inhibitor with
      antiplatelet and antithrombotic properties, inhibits lipopolysaccharide (LPS)
      induced MCP-1 and MMP-9 expression. In a rabbit aorta balloon-injury model,
      administration of LPS increased macrophage infiltration and MCP-1 and MMP-9
      expression; cilostazol supplementation prevented this phenomenon and reduced
      intimal hyperplasia. In contrast, the reverse zymography showed that cilostazol
      did not affect TIMP-1 expression in serum. In monocytic THP-1 cells, cilostazol
      and N6,O2'-dibutyryl-cAMP (dioctanoyl-cAMP, a cAMP analog) dose-dependently
      inhibited LPS-induced MCP-1 protein expression and MMP-9 activation, but did not
      affect the tissue inhibitor of metalloproteinase-1. Quantitative real-time
      polymerase chain reaction (PCR) showed that cilostazol inhibited MCP-1 and MMP-9
      mRNA expression. Cilostazol significantly inhibited LPS-induced activation of
      p38, JNK, and nuclear factor-kappaB, and the respective inhibitors of p38 and JNK
      greatly reduced the level of LPS-induced MCP-1 and MMP-9, suggesting the
      involvement of the p38 and JNK pathways. In conclusion, cilostazol administered
      with LPS in vivo reduced neointimal hyperplasia and macrophage infiltration in
      the balloon-injured rabbit aorta; in vitro, cilostazol inhibits LPS-induced MCP-1
      and MMP-9 expression. These data suggest that cilostazol may play an important
      role in preventing endotoxin- and injured-mediated vascular inflammation.

PMID- 17516548
TI  - The 3111T/C polymorphism of the CLOCK gene confers a predisposition to a lifetime
      lower body weight in patients with anorexia nervosa and bulimia nervosa: a
      preliminary study.
AB  - Feeding is subjected to circadian regulation; therefore, changes in the
      components of the endogenous oscillator regulating circadian rhythms may be
      involved in disordered rhythmicity of eating behavior as it occurs in anorexia
      nervosa (AN) and bulimia nervosa (BN). We investigated whether the 3111T/C
      polymorphism of the CLOCK gene, which is part of the endogenous oscillator
      system, was associated to AN and/or BN. A total of 241 women, including 90
      healthy controls, 60 patients with AN and 91 patients with BN, participated into
      the study. The frequencies of 3111T/C genotypes and alleles did not significantly
      differ among the groups. In both the AN and BN group, subjects carrying one copy
      of the C allele had a lifetime body weight significantly lower than those
      carrying the T/T genotype. These findings, although preliminary, suggest that the
      3111T/C polymorphism of the CLOCK gene does not play a major role in the genetic
      vulnerability to AN and BN, but it seems to predispose eating disorders (EDs)
      patients to a more severe lifetime body weight loss.

PMID- 17516549
TI  - Radiation-induced bystander effects in malignant trophoblast cells are
      independent from gap junctional communication.
AB  - It is controversially discussed that irradiation induces bystander effects via
      gap junction channels and/or diffusible cellular factors such as nitric oxide or
      cytokines excreted from the cells into the environment. But up to now the
      molecular mechanism leading to a bystander response is not well understood. To
      discriminate between both mechanisms of bystander response, (i) mediated by gap
      junctional communication and/or (ii) mediated by diffusible molecules, we used
      non-communicating Jeg3 malignant trophoblast cells transfected with inducible gap
      junction proteins, connexin43 and connexin26, respectively, based on the Tet-On
      system. We co-cultivated X-ray irradiated and non-irradiated bystander Jeg3 cells
      for 4 h, separated both cell populations by flow cytometry and evaluated the
      expression of activated p53 by Western blot analysis. The experimental design was
      proven with communicating versus non-communicating Jeg3 cells. Interestingly, our
      results revealed a bystander effect which was independent from gap junctional
      communication properties and the connexin isoform expressed. Therefore, it seems
      more likely that the bystander effect is not mediated via gap junction channels
      but rather by paracrine mechanisms via excreted molecules in Jeg3 cells.

PMID- 17516550
TI  - Differential calreticulin expression affects focal contacts via the
      calmodulin/CaMK II pathway.
AB  - Calreticulin is an ER calcium-storage protein, which influences gene expression
      and cell adhesion. In this study, we analysed the differences in adhesive
      properties of calreticulin under- and overexpressing fibroblasts in relation to
      the calmodulin- and calcium/calmodulin-dependent kinase II (CaMK II)-dependent
      signalling pathways. Cells stably underexpressing calreticulin had elevated
      expression of calmodulin, activated CaMK II, activated ERK and activated c-src.
      Inhibition of calmodulin by W7, and CaMK II by KN-62, caused the otherwise weekly
      adhesive calreticulin underexpressing cells to behave like the overexpressing
      cells, via induction of increased cell spreading. Increased vinculin, activated
      paxillin, activated focal adhesion kinase and fibronectin levels were observed
      upon inhibition of either the calmodulin or the CaMK II signalling pathways,
      which was accompanied by an increase in cell spreading and focal contact
      formation. Both KN-62 and W7 treatment increased cell motility in underexpressing
      cells, but W7 treatment led to loss of directionality. Thus, both the calmodulin
      and CaMK II signalling pathways influence cellular spreading and motility, but
      subtle differences exist in their distal effects on motility effectors.

PMID- 17516551
TI  - Increased Ca2+ storage capacity of the skeletal muscle sarcoplasmic reticulum of
      transgenic mice over-expressing membrane bound calcium binding protein junctate.
AB  - Junctate is an integral sarco(endo)plasmic reticulum protein expressed in many
      tissues including heart and skeletal muscle. Because of its localization and
      biochemical characteristics, junctate is deemed to participate in the regulation
      of the intracellular Ca2+ concentration. However, its physiological function in
      muscle cells has not been investigated yet. In this study we examined the effects
      of junctate over-expression by generating a transgenic mouse model which over
      expresses junctate in skeletal muscle. Our results demonstrate that junctate over
      expression induced a significant increase in SR Ca2+ storage capacity which was
      paralleled by an increased 4-chloro-m-cresol and caffeine-induced Ca2+ release,
      whereas it did not affect SR Ca2+-dependent ATPase activity and SR Ca2+ loading
      rates. In addition, junctate over-expression did not affect the expression levels
      of SR Ca2+ binding proteins such as calsequestrin, calreticulin and sarcalumenin.
      These findings suggest that junctate over-expression is associated with an
      increase in the SR Ca2+ storage capacity and releasable Ca2+ content and support
      a physiological role for junctate in intracellular Ca2+ homeostasis.

PMID- 17516552
TI  - Novel approaches for gene-specific interference via manipulating actions of
      microRNAs: examination on the pacemaker channel genes HCN2 and HCN4.
AB  - Recent evidence has suggested microRNAs as viable therapeutic targets for a wide
      range of human disease. However, lack of gene-specificity of microRNA actions may
      hinder this application. Here we developed two new approaches, the gene-specific
      microRNA mimic and microRNA-masking antisense approaches, to explore the
      possibility of using microRNA's principle of actions in a gene-specific manner.
      We examined the value of these strategies as rational approaches to develop heart
      rate-reducing agents and "biological pacemakers" by manipulating the expression
      of the cardiac pacemaker channel genes HCN2 and HCN4. We showed that the gene
      specific microRNA mimics, 22-nt RNAs designed to target the 3'untranslated
      regions (3'UTRs) of HCN2 and HCN4, respectively, were efficient in abrogating
      expression and function of HCN2 and HCN4. The gene-specific microRNA mimics
      repressed protein levels, accompanied by depressed f-channel conductance and the
      associated rhythmic activity, without affecting mRNA levels of HCN2 and HCN4.
      Meanwhile, we also designed the microRNA-masking antisense based on the miR-1 and
      miR-133 target sites in the 3'UTRs of HCN2 and HCN4 and found that these
      antisense oligodeoxynucleotides markedly enhanced HCN2/HCN4 expression and
      function, as reflected by increased protein levels of HCN2/HCN4 and If
      conductance, by removing the repression of HCN2/HCN4 expression induced by
      endogenous miR-1/miR-133. The experimental examination of these techniques and
      the resultant findings not only indicate feasibility of interfering miRNA action
      in a gene-specific fashion but also may provide a new research tool for studying
      function of miRNAs. The new approaches also have the potential of becoming
      alternative gene therapy strategies.

PMID- 17516553
TI  - Bone morphogenetic protein 4 induces epithelial-mesenchymal transition through
      MSX2 induction on pancreatic cancer cell line.
AB  - In our study, we found that bone morphogenetic protein 4 (BMP4) has a novel
      effect as an inducer of epithelial-mesenchymal transition (EMT) on Panc-1 cells,
      a human pancreatic carcinoma cell line. BMP4-treated Panc-1 cells showed loose
      cell contacts and a scattered, fibroblast-like appearance along with E-cadherin
      downregulation, Vimentin upregulation and enhanced cell migration, which are
      characteristic of EMT. BMP4 treatment also induced homeobox gene MSX2 expression,
      which we previously showed to be associated with EMT in pancreatic carcinoma
      cells. BMP4 treatment activated the Smad signaling pathway, and extracellular
      signal-related kinase (ERK) and p38 mitogen-activated kinase (MAPK) pathways in
      these cells. MSX2 was markedly induced by BMP4 through the ERK and p38 MAPK
      pathways in collaboration with the Smad signaling pathway. The repression of E
      cadherin, induction of Vimentin and enhanced cell migration disappeared when
      siRNA-based MSX2 downregulated pancreatic cancer cells were treated with BMP4.
      These findings indicate that BMP4 may be involved in pancreatic carcinoma
      development through the promotion of EMT and that MSX2 is indispensable to this
      process.

PMID- 17516554
TI  - Dystroglycan expression is reduced during prostate tumorigenesis and is regulated
      by androgens in prostate cancer cells.
AB  - Prostate cancer, the most frequently diagnosed cancer in Western men, can display
      a high variability in term of clinical aggressiveness and prognosis and none of
      the available markers is able to accurately predict its clinical course.
      Dystroglycan (DG), a non-integrin adhesion molecule, is a complex formed by two
      subunits, alpha- and beta-DG, which bind to extracellular matrix molecules and
      cytoskeleton, respectively. DG expression is frequently reduced in human cancers
      and has been related to tumor grade and aggressiveness. This study investigated
      the role of DG in human prostate tumorigenesis and its suitability as a
      prognostic marker. The expression level of extracellular alpha-DG subunit was
      frequently reduced in human prostate cancer cell lines and primary tumors and the
      percentage of positive tumor cells was significantly further decreased in vivo
      following androgen ablation therapy (median = 1%) compared to pre-treatment
      samples (median = 28%). A significant relationship was observed between alpha-DG
      staining on the post-treatment samples and tumor recurrence. A dose- and time
      dependent decrease of DG expression also occurred in human prostate cancer cells
      following treatment with the anti-androgen flutamide. Stable expression of an
      exogenous DG cDNA in the LNCaP human prostate carcinoma cell line resulted in a
      marked inhibition of both anchorage-dependent and independent growth and of the
      in vivo tumorigenicity. These findings confirm and extend previous evidence that
      disturbances in the function of the DG complex might contribute to the definition
      of the malignant behavior of prostate cancer cells and suggest that androgens
      might regulate DG expression in these cells.

PMID- 17516555
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases Bovine Herpesvirus type-1 (BHV-1)
      replication in Madin-Darby Bovine Kidney (MDBK) cells in vitro.
AB  - Dioxin-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental toxin
      of current interest. In the last years, higher levels of TCDD than those
      permitted in UE [European Commission. 2002. European Commission Recommendation
      2002/201/CE. Official Gazette, L 67/69] were detected in milk samples from cow,
      water buffalo, goat, and sheep raised on some areas of Campania Region (South
      Italy). Dioxin often causes immunosuppression and might render the animal liable
      to viral infections. In addition, viral infections are able to alter the pattern
      of dioxin distribution in different organs of the exposed animals. Bovine
      Herpesvirus type-1 (BHV-1) is a widespread pathogen, which causes infectious
      rhinotracheitis and infectious pustular vulvovaginitis in cattle. Herein, we have
      studied the effects of TCDD and BHV-1 infection, in Madin-Darby Bovine Kidney
      (MDBK) cells, alone as well as in association, so as cellular proliferation,
      apoptosis, and virus replication. We have observed an increase in cell viability
      of confluent monolayers at low TCDD concentrations. TCDD treated cells
      demonstrated increased viability compared to controls as evaluated by MTT test.
      TCDD exposure increased cell proliferation but induced no changes on apoptosis.
      Cells exposed to TCDD along with BHV-1 showed a dose-dependent increase in
      cytopathy, represented by ample syncytia formation with the elimination of the
      cellular sheets and increased viral titer. These results suggest that TCDD
      increases viral replication in MDBK cells while BHV-1 further decreases viability
      of TCDD exposed cells. Since very low concentrations (0.01 pg/ml) are sufficient
      to augment BHV-1 titer, TCDD may contribute to reactivate BHV-1 from latency,
      leading to recurrent disease and increase virus transmission.

PMID- 17516557
TI  - The journal: a retrospective.
AB  - With this issue, The Mount Sinai Journal of Medicine moves from being a general
      medical publication to one specializing in translational and personalized
      medicine. This article traces the history of The Journal from its beginning in
      1934 to the present day. The Editors and their editorial policies are discussed,
      with mention of many articles over the years that have made the Journal truly a
      part of Mount Sinai's history.

PMID- 17516558
TI  - A "lugged" analysis of lung cancer risks in UK carbon black production workers,
      1951-2004.
AB  - BACKGROUND: Previously published analyses of excess lung cancer risks in UK
      carbon black production workers attracted no confident interpretation. METHODS:
      The mortality of a cohort of 1,147 male manual workers from five UK factories
      manufacturing carbon black was investigated for the period 1951-2004. All
      subjects were first employed in the period 1947-74 and were employed for 12
      months or more. Limited work histories were available to calculate estimates of
      individual cumulative exposure to carbon black. RESULTS: Based on serial rates
      for the general population of England and Wales, significantly elevated mortality
      was observed for lung cancer (Obs 67, SMR 146, P < 0.01) but not for all other
      causes combined (Obs 426, SMR 106). There was highly elevated lung cancer
      mortality at two of the plants (SMR 230, Obs 35) but no excess mortality at the
      other three plants combined (SMR 104, Obs 32). Analyses by period since leaving
      employment indicated elevated lung cancer risks were limited to those workers
      with some employment in the most recent 15 years. SMR analyses found an overall
      positive significant trend between lung cancer risks and cumulative carbon black
      exposure received in the most recent 15 years. Poisson regression analyses
      provided different results depending on which variables were adjusted for.
      CONCLUSIONS: The findings suggest that carbon black, or chemicals associated with
      the production of carbon black, had an effect on later stages of lung cancer
      carcinogenesis at two of the plants but that no such effect was found at the
      other plants.

PMID- 17516559
TI  - Translational experimental therapeutics: The translation of laboratory-based
      discovery into disease-related therapy.
AB  - In the past decade, there has been an increasing emphasis on laboratory-based
      translational research. This has led to significant scientific advances in our
      understanding of disease mechanisms and in the development of novel approaches to
      therapy such as gene therapy, RNA interference, and stem cells. However, the
      translation of these remarkable scientific achievements into new and effective
      disease-modifying therapies has lagged behind these scientific accomplishments.
      We use the term "translational experimental therapeutics" to describe the pathway
      between the discovery of a basic disease mechanism or novel therapeutic approach
      and its translation into an effective treatment for patients with a specific
      disease. In this article, we review the components of this pathway, and discuss
      issues that might impede this process. Only by optimizing this pathway can we
      realize the full therapeutic potential of current scientific discoveries and
      translate the astounding advances that have been accomplished in the laboratory
      into effective treatments for our patients.

PMID- 17516560
TI  - Network analysis of FDA approved drugs and their targets.
AB  - The global relationship between drugs that are approved for therapeutic use and
      the human genome is not known. We employed graph-theory methods to analyze the
      Federal Food and Drug Administration (FDA) approved drugs and their known
      molecular targets. We used the FDA Approved Drug Products with Therapeutic
      Equivalence Evaluations 26(th) Edition Electronic Orange Book (EOB) to identify
      all FDA approved drugs and their active ingredients. We then connected the list
      of active ingredients extracted from the EOB to those known human protein targets
      included in the DrugBank database and constructed a bipartite network. We
      computed network statistics and conducted Gene Ontology analysis on the drug
      targets and drug categories. We find that drug to drug-target relationship in the
      bipartite network is scale-free. Several classes of proteins in the human genome
      appear to be better targets for drugs since they appear to be selectively
      enriched as drug targets for the currently FDA approved drugs. These initial
      observations allow for development of an integrated research methodology to
      identify general principles of the drug discovery process.

PMID- 17516561
TI  - Job of the Bible: leprosy or scabies?
AB  - Proposing a medical diagnosis a posteriori of a person who died a long time ago
      is not as impossible as it sounds if sufficient medical history is available.A
      whole book of the Bible is devoted to Job and his trials. The diagnosis of
      leprosy has been generally accepted by medieval commentators because the verses
      of the Book speak of ulcers disseminated over the skin, and also because leprosy
      is an exemplary sanction imposed by way of example by God to punish those who
      have committed a sin. In this paper, we have taken the different verses with a
      medical content from the Book of Job, and reconstructed the clinical picture as
      if the patient had turned up in the 21st century in order to see if the diagnosis
      of leprosy may be called into question, and to discuss the limits of the medico
      historic approach. The clinical picture of the disease consists of deterioration
      in the general condition, with widespread pain, confusion, skin eruptions,
      bilious vomiting, and so on. Under these conditions, if Job did exist, and if the
      retrospective medical history is reliable, the most likely diagnosis is that of
      scabies rather than leprosy.

PMID- 17516562
TI  - Foundations, promises and uncertainties of personalized medicine.
AB  - Personalized medicine introduces the promise to use molecular markers that signal
      the risk of disease or its presence before clinical signs and symptoms appear.
      This information underlies a new healthcare strategy focused on prevention and
      early intervention, rather than reaction to advanced stages of disease. Such a
      strategy can delay disease onset or minimize symptom severity. The molecular
      foundations that enable personalized medicine include detection of variation in
      nucleotide sequence of genes and in characteristic patterns of gene expression,
      proteins and metabolites. Genetic and molecular patterns are correlated with
      disease manifestations, drug responses, treatment prognosis, or prediction of
      predisposition to future disease states. However, the uncertainties for
      personalized medicine are considerable, including economic, ethical, legal, and
      societal questions. Although much of its promise remains unproven to date, the
      foundations of personalized medicine appear solid and evidence is accumulating
      rapidly pointing to its growing importance in healthcare (Fig. 1).

PMID- 17516563
TI  - The role of the pathologist in translational and personalized medicine.
AB  - Over the years, pathologists have served to make morphologic diagnoses for
      clinicians when provided with a biopsy or surgically resected tissue specimen.
      Traditionally, pathologists have used a series of morphologic techniques and
      relied on the microscopic appearance of resected tissues to determine a
      pathologic diagnosis and, with respect to neoplastic lesions, provide predictions
      of the potential growth pattern that might be anticipated. With the introduction
      of the techniques of molecular biology in medicine, the role of the pathologist
      has changed as have the tools available for characterizing pathologic specimens.
      With the pathologist's unique perspective on disease processes and access to
      tissue specimens from the operating room, he has become a key player in the area
      of translational and personalized medicine and the development of new approaches
      to diagnosis and translational research.

PMID- 17516564
TI  - Handwashing and infection control.

PMID- 17516565
TI  - Apparent mineralocorticoid excess manifested in an elderly patient with
      hypothyroidism.

PMID- 17516566
TI  - Mechanisms of uremic erythrocyte-induced adhesion of human monocytes to cultured
      endothelial cells.
AB  - In end-stage renal disease (ESRD) endothelium may represent a key target for the
      action of circulating elements, such as modified erythrocytes (RBC) and/or
      plasmatic factors, that may facilitate inflammation and the vasculopathy
      associated with uremia. We have previously demonstrated that phosphatidylserine
      (PS) exposure on the surface of RBC from ESRD patients increases RBC-human
      umbilical vein endothelial cell (HUVEC) interactions and causes decreased nitric
      oxide (NO) production. We postulated that, besides the pro-inflammatory effects
      due to decreased NO bio-availability, enhanced ESRD-RBC-HUVEC interactions might
      directly stimulate pro-inflammatory pathways leading to increased vascular
      adhesion molecule expression. ESRD-RBC-endothelial cell interactions induced a
      time-dependent up-regulation of VCAM-1 and ICAM-1 (measured by Western blot (WB)
      and real-time PCR), associated with mitogen-activated protein kinase (MAPK)
      activation and impairment of the Akt/endothelial nitric oxide synthase (eNOS)
      signaling cascade, measured by WB. In reconstitution experiments, normal RBC
      incubated with uremic plasma showed increased PS exposure and significantly
      increased VCAM-1 and ICAM-1 mRNA levels when incubated on HUVEC. Interestingly,
      ESRD-RBC induced increased expression of adhesion molecules was prevented by
      Annexin-V (AnV, able to mask PS on RBC surface), anti-integrin-alpha(v)beta3,
      anti-thrombospondin-1 (TSP-1), and PD98059 (a selective inhibitor of MAPK
      phosphorylation). Moreover, AnV reversed the ESRD-RBC effects on MAPK and
      Akt/eNOS signaling pathways. Our data demonstrate that, possibly via a direct
      interaction with the endothelial thrombospondin-(alpha(v)beta3) integrin complex,
      ESRD-RBC-HUVEC adhesion induces a vascular inflammatory phenotype. Thus,
      intervention targeting ESRD-RBC increased adhesion to endothelium and/or MAPK and
      Akt/eNOS pathways may have the potential to prevent vascular lesions under uremic
      conditions.

PMID- 17516567
TI  - Exogenous hydrogen sulfide induces functional inhibition and cell death of
      cytotoxic lymphocytes subsets.
AB  - The toxic effects of exogenous hydrogen sulfide on peripheral blood lymphocytes
      have been investigated in detail. Hydrogen sulfide is now considered as a
      gasotransmitter with specific functional roles in different cell types, like
      neurons and vascular smooth muscle. Here we show that exogenous hydrogen sulfide
      induces a caspase-independent cell death of peripheral blood lymphocytes that
      depends on their intracellular glutathione levels, with a physiologically
      relevant subset specificity for CD8+ T cells and NK cells. Although lymphocyte
      activation does not modify their sensitivity to HS-, after 24 h exposure to
      hydrogen sulfide surviving lymphocyte subsets show a dramatically decreased
      proliferation in response to mitogens and a reduced IL-2 production. Overall, our
      data demonstrate that HS- reduces the cellular cytotoxic response of peripheral
      blood lymphocytes as well as their production of IL-2, therefore de-activating
      the major players of local inflammatory responses, adding new basic knowledge to
      the clinically well known anti-inflammatory effects of sulfur compounds.

PMID- 17516568
TI  - PSMD9 gene variants within NIDDM2 may rarely contribute to type 2 diabetes.
AB  - Multiple genome-wide scans in different populations have linked the chromosome
      12q24 region, known as NIDDM2 (non-insulin-dependent-diabetes, locus 2), to type
      2 diabetes. Within NIDDM2 we examined the PSMD9 (proteasome modulator 9/Bridge-1)
      gene that encodes a PDZ-domain transcriptional coactivator of insulin production.
      Our goal was to identify a potential contribution of the PSMD9 gene to type 2
      diabetes in Italians. We directly sequenced the entire gene PSMD9 in Italian type
      2 diabetes patients (n = 237) and controls subjects (n = 215) and performed an
      association study with the identified gene variants. We found five single
      nucleotide polymorphisms (SNPs), A17V, IVS1+nt29, IVS3+nt460, IVS3+nt437, and
      E197G, which are not associated with disease in our case-control study.
      Furthermore, we identified two PSMD9 gene variants in type 2 diabetes patients,
      which produced nonconservative amino acid substitutions S143G and N166S within
      the PDZ domain and two other gene variants. Three out of four of these variants
      are absent from the control subjects screened. We propose that the three PSMD9
      gene variants (S143G, N166S and G > A at IVS3+nt102), absent in control subjects,
      contribute rarely to late-onset type 2 diabetes in Italians. In fact, the
      frequency rate of such variants in unrelated cases equals 0.016. We may not
      exclude that PSMD9 gene variants may contribute, either commonly or rarely, to an
      increased risk of type 2 diabetes in other populations.

PMID- 17516569
TI  - Expanding the lysyl hydroxylase toolbox: new insights into the localization and
      activities of lysyl hydroxylase 3 (LH3).
AB  - Hydroxylysine and its glycosylated forms, galactosylhydroxylysine and
      glucosylgalactosylhydroxylysine, are post-translational modifications unique to
      collagenous sequences. They are found in collagens and in many proteins having a
      collagenous domain in their structure. Since the last published reviews,
      significant new data have accumulated regarding these modifications. One of the
      lysyl hydroxylase isoforms, lysyl hydroxylase 3 (LH3), has been shown to possess
      three catalytic activities required sequentially to produce hydroxylysine and its
      glycosylated forms, that is, the lysyl hydroxylase (LH), galactosyltransferase
      (GT), and glucosyltransferase (GGT) activities. Studies on mouse models have
      revealed the importance of these different activities of LH3 in vivo. LH3 is the
      main molecule responsible for GGT activity in mouse embryos. A lack of this
      activity causes intracellular accumulation of type IV collagen, which disrupts
      the formation of basement membranes (BMs) during mouse embryogenesis and leads to
      embryonic lethality. The specific inactivation of the LH activity of LH3 causes
      minor alterations in the structure of the BM and collagen fibril organization,
      but does not affect the lifespan of mutated mice. Recent data from zebrafish
      demonstrate that growth cone migration depends critically on the LH3
      glycosyltransferase domain. LH3 is located in the ER loosely associated with the
      membranes, but, unlike the other isoforms, LH3 is also found in the extracellular
      space in some tissues. LH3 is able to adjust the amount of hydroxylysine and
      hydroxylysine-linked carbohydrates of extracellular proteins in their native
      conformation, suggesting that it may have a role in matrix remodeling.

PMID- 17516570
TI  - Exploration of target molecules for prostate cancer gene therapy.
AB  - BACKGROUND: Focusing on Adv-FZ33, a modified adenovirus in which a synthetic 33
      amino-acid immunoglobulin G-binding domain was inserted into the adenoviral fiber
      protein, we tried to identify suitable target molecules for prostate cancer
      specific gene therapy. METHODS: Hybridomas were established from mice immunized
      with prostate cancer cell lines. The hybridomas were screened using Adv-FZ33 to
      create monoclonal antibodies (mAbs) that induced high gene transfer efficiency
      for PC-3 cells. Furthermore, we identified target antigens of the mAbs by
      immunoprecipitation and mass spectrometry, and investigated the expression of
      target molecules by flow cytometry and immunocytochemistry. RESULTS: Using Adv
      FZ33, we established four different mouse mAbs that increased transduction
      efficiency for PC-3. The target antigens identified were Ep-CAM, CD155, HAI-1,
      and Na,K-ATPase beta1. These antigens were expressed in several cancer cell
      lines, including prostate cancer. Human prostatic myofibroblast cells lacked
      expression of Ep-CAM and HAI-1. CONCLUSIONS: We established anti-Ep-CAM mAb and
      anti- HAI-1 mAbs. Gene transduction via Ep-CAM and HAI-1 may be a novel strategy
      for treatment of prostate cancer.

PMID- 17516571
TI  - A population study of neutering status as a risk factor for canine prostate
      cancer.
AB  - BACKGROUND: Prostate cancer has been reported to occur more commonly in neutered
      than intact male dogs in several case series. This study was undertaken to
      evaluate risk of prostate cancer in a large population database. The hypothesis
      was that castration is a risk factor for prostate cancer in male companion dogs.
      METHODS: Data were derived from recorded visits to North American veterinary
      teaching hospitals. The Veterinary Medical Databases (VMDB) were queried to yield
      male dogs with urinary bladder transitional cell carcinoma (TCC), prostate
      adenocarcinoma (ACA), prostate TCC, prostate carcinoma (CA), and prostate tumors.
      A second query yielded all male dogs over the age of 4 years without a diagnosis
      of urinary tract cancer. These populations were compared to determine relative
      risks for developing each disease, singly and collectively, associated with
      neutering status. Odds ratios were calculated for breed as a risk factor.
      RESULTS: Neutered males had a significantly increased risk for each form of
      cancer. Neutered males had an odds ratio of 3.56 (3.02-4.21) for urinary bladder
      TCC, 8.00 (5.60-11.42) for prostate TCC, 2.12 (1.80-2.49) for prostate
      adenocarcinoma, 3.86 (3.13-4.16) for prostate carcinoma, and 2.84 (2.57-3.14) for
      all prostate cancers. Relative risks were highly similar when cases were limited
      to those with a histologically confirmed diagnosis. CONCLUSIONS: Breed
      predisposition suggests that genetic factors play a role in the development of
      prostate cancer. The risk associated with being neutered is highest for TCC,
      supporting previous work identifying the urothelium and ductular rather than
      acinar epithelium as the source of these tumors.

PMID- 17516572
TI  - Rapamycin inhibits osteoblast proliferation and differentiation in MC3T3-E1 cells
      and primary mouse bone marrow stromal cells.
AB  - While the roles of the mammalian target of rapamycin (mTOR) signaling in
      regulation of cell growth, proliferation, and survival have been well documented
      in various cell types, its actions in osteoblasts are poorly understood. In this
      study, we determined the effects of rapamycin, a specific inhibitor of mTOR, on
      osteoblast proliferation and differentiation using MC3T3-E1 preosteoblastic cells
      (MC-4) and primary mouse bone marrow stromal cells (BMSCs). Rapamycin
      significantly inhibited proliferation in both MC-4 cells and BMSCs at a
      concentration as low as 0.1 nM. Western blot analysis shows that rapamycin
      treatment markedly reduced levels of cyclin A and D1 protein in both cell types.
      In differentiating osteoblasts, rapamycin dramatically reduced osteoblast
      specific osteocalcin (Ocn), bone sialoprotein (Bsp), and osterix (Osx) mRNA
      expression, ALP activity, and mineralization capacity. However, the drug
      treatment had no effect on osteoblast differentiation parameters when the cells
      were completely differentiated. Importantly, rapamycin markedly reduced levels of
      Runx2 protein in both proliferating and differentiating but not differentiated
      osteoblasts. Finally, overexpression of S6K in COS-7 cells significantly
      increased levels of Runx2 protein and Runx2 activity. Taken together, our studies
      demonstrate that mTOR signaling affects osteoblast functions by targeting
      osteoblast proliferation and the early stage of osteoblast differentiation.

PMID- 17516573
TI  - ds-Oligonucleotide-peptide conjugates featuring peptides from the leucine-zipper
      region of Fos as switchable receptors for the oncoprotein Jun.

PMID- 17516574
TI  - Cu(I)-catalyzed conjugate addition of ethyl propiolate.

PMID- 17516577
TI  - Synthesis and anti-proliferative in-vitro activity of two natural
      dihydrostilbenes and their analogues.
AB  - A total synthetic route for two natural dihydrostilbenes with significant
      cytotoxicity toward human cancer cell lines, (3-(2-(7-methoxybenzo[d][1,3]dioxol
      5-yl)ethyl)phenol 1a and 6-(3-hydroxyphenethyl)benzo[d][1,3]dioxol-4-ol 1b),
      which were isolated from Bulbophyllum odoratissimum Lindl, was developed via
      Wittig-Horner reaction. The natural products 1a and 1b were obtained in 28% and
      20% overall yield, respectively. Additionally, nine analogues, 1c-1k, of the two
      natural dihydrostilbenes were synthesized and evaluated for their anti
      proliferative activity against human SGC-7901, KB and HT-1080 cell lines by MTT
      assay. The activities of 1c and 1d were in the same range as those of the natural
      products 1a and 1b.

PMID- 17516578
TI  - The oriented development of antituberculotics (Part II): halogenated 3-(4
      alkylphenyl)-1,3-benzoxazine-2,4-(3H)-diones.
AB  - Based on our previous studies, 21 new halogenated 3-(4-alkylphenyl)-1,3
      benzoxazine-2,4-(3H)-diones were synthesized by the reaction of salicylanilides
      and methyl-chloroformate. All compounds were screened in vitro against three
      different strains of mycobacterium, and Free-Wilson method was used to establish
      structure-activity relationships. 6-Bromo-3-(4-butylphenyl)-1,3-benzoxazine-2,4
      (3H)-dione 3b proved to be the most active compound of the series.

PMID- 17516579
TI  - Silver- and Coomassie-staining protocols: detection limits and compatibility with
      ESI MS.
AB  - Staining protocols for PAGE have to be sensitive and should not impair further MS
      analysis of selected samples. In this study, the MS compatibility of different
      silver- and Coomassie-staining protocols with a nano-LC-MS/MS system was
      systematically elucidated. Altogether, 13 different silver-staining, 1 imidazole
      staining and 2 Coomassie-staining protocols were used and compared to each other
      for their achieved sequence coverage and their detection sensitivity. Three
      proteins were used as model proteins (bovine serum albumin, rabbit L-lactate
      dehydrogenase, bovine milk beta-lactoglobulin) in decreasing concentration (12
      pmol down to 30 fmol) and different staining protocols were applied. The
      conclusion of this study is that two silver-staining protocols (Blum, H. et al.,.
      Electrophoresis 1987, 8, 93-99 and Shevchenko, A. et al.,. Anal. Chem. 1996, 68,
      850-858) combine good sequence coverage and good sensitivity and are recommended
      for nano-LC-MS/MS analysis.

PMID- 17516580
TI  - What does it need to be a biomarker? Relationships between resolution,
      differential quantification and statistical validation of protein surrogate
      biomarkers.
AB  - The separation of proteins with the aim of discovering surrogate biomarkers
      defining differences between various stages of biological materials is the core
      occupation of every project in Proteomics. There are numerous recent publications
      suggesting a wide array of separation technologies, ranging from 2-DE, MS-linked
      LC, CE or chip-based surface-enhanced laser desorption ionization claiming to be
      useful for this purpose, and addressing the urgent clinical, diagnostic or
      toxicological needs for such surrogates. However, many potential biomarkers
      emerging from proteomic studies did not survive validation in, for example, large
      scale clinical studies or simply independent experiments, and at the same time
      being tested in settings with case numbers bigger than perhaps a few hundreds.
      The major problems of protein biomarkers are associated with the huge dynamic
      range of possible concentrations and the ever-increasing number of molecular
      species due to post-translational modifications. In particular, the chemical
      diversity of the latter imposes a necessity of improved resolution of separation
      technologies, because otherwise the crucial quantitative information is lost in
      pools of poorly resolved peptides. Here, we present and analyze some examples of
      successful developments of protein biomarkers, and show the prerequisites and
      necessary considerations while moving protein candidates from purely descriptive
      phenomena to a stage of validated surrogate biomarkers. This includes a detailed
      discussion of requirements regarding resolution of initial separation techniques,
      linear dynamic range and statistics of differential quantification, but also the
      subsequent clinical validation, testing the biomarker in clinical settings and
      using large numbers of patient samples.

PMID- 17516581
TI  - Interrogation of MS/MS search data with an pI Filter algorithm to increase
      protein identification success.
AB  - In high-throughput proteomics, the bottom-up approach has become a widely used
      method for the identification of proteins that is based on tryptic peptide MS/MS
      analysis. Separation methodologies that use IEF of tryptic peptides have recently
      been introduced and provide an extra dimension of peptide separation. In addition
      to its great fractionation capability, tryptic peptide prefractionation by IEF
      can also increase the protein identification success. The pI information of the
      peptide gained can be successfully used in a post-database search filtering step.
      We introduce a filtering algorithm that is based on the comparison of the
      experimental and theoretical pI's to validate peptide identifications by MS/MS
      data search engines.

PMID- 17516582
TI  - CE assay of methylmalonyl-coenzyme-a mutase activity.
AB  - Methylmalonyl-coenzyme A mutase (MCM) is a 5'-deoxyadenosylcobalamin-linked
      mitochondrial enzyme that catalyzes the isomerization of L-methylmalonyl-coenzyme
      A to succinyl-coenzyme A. We described a method for methylmalonyl-CoA and
      succinyl-CoA separation by CE, suitable for the evaluation of MCM activity. The
      working conditions for optimal separation were obtained in order to achieve the
      best resolution in the shortest analysis time. The optimization of buffer
      composition together with other variables, such as injection time, separation
      voltage, migration time, and capillary temperature, resulted in a solution of 30
      mM NaH2PO4 containing 15 mM SDS, pH 3.2. Separations were carried out in an
      uncoated fused-silica capillary (55 cm, 50 microm id) at -25 kV, reading at 254
      nm. The method performance was evaluated by measuring total and holo-MCM activity
      in biological matrices such as rat liver and human peripheral blood lymphocytes
      (PBL). The mean MCM activity was expressed in nmol/h/mg protein of tissue/cell
      extract and was calculated from the amount of reaction product formed. The
      rapidity of analysis and utmost precision (repeatability and within-laboratory
      reproducibility) point out the potentialities of the proposed method for the
      differential diagnosis of methylmalonic acidemia, in relation to protein or
      coenzyme defects.

PMID- 17516583
TI  - Social capital and its relationship with measures of health status: evidence from
      the Health Survey for England 2003.
AB  - Social capital is a concept that attempts to describe the quantity and quality of
      social interactions in a community. This study explores the relationship between
      individual measures of social capital and alternative measures of health status
      within the context of a large national survey of population health. Using data
      for 13 753 adult participants in the 2003 Health Survey for England, linear
      regression with weighted least-squares estimation and Tobit regression with upper
      censoring were used to model the relationship between individual measures of
      social capital and EQ-5D utility scores. In addition, logistic regression was
      used to model the relationship between individual measures of social capital and
      a dichotomous self-reported health status variable. The study demonstrated that
      low stocks of social capital across the domains of trust and reciprocity,
      perceived social support and civic participation are significantly associated
      with poor measures of health status. The implications for health economists and,
      potentially, for policymakers are discussed.

PMID- 17516584
TI  - Role of APAF-1, E-cadherin and peritumoral lymphocytic infiltration in tumour
      budding in colorectal cancer.
AB  - Tumour budding or dedifferentiation at the invasive margin of colorectal cancer
      (CRC) is an important prognostic marker and linked mechanistically to
      dysregulation of Wnt pathway signalling. Since budding is observed in only 40% of
      CRCs, we hypothesized that Wnt pathway dysregulation may be a necessary but
      insufficient explanation for budding and that buds may be destroyed selectively
      by tumour immune mechanisms. Twenty potential markers of tumour budding were
      evaluated in tissue microarrays (TMAs) obtained from the main tumour body of 1164
      DNA mismatch repair-proficient CRCs and the findings were correlated with tumour
      budding, lymphocytic infiltration and survival. Loss of expression of E-cadherin
      and APAF-1 were independent predictors of budding (sensitivity 70.3% and
      specificity 48.2% when one or the other was lost). Peritumoral lymphocytes (PTLs)
      were observed more frequently in CRCs with loss of either E-cadherin or APAF-1
      that were budding-negative. PTLs and tumour-infiltrating lymphocytes (TILs) were
      strongly correlated. The absence of TILs increased the adverse prognostic impact
      of E-cadherin and APAF-1 loss. Co-occurrence of E-cadherin loss, APAF-1 loss and
      low TIL counts in CRCs was an independent prognostic factor. The findings were
      verified in whole tissue sections from 88 CRCs with known KRAS mutation status
      (which was not associated with budding). Loss of E-cadherin and APAF-1 within the
      main body of CRCs are independent predictors of tumour budding. The prognostic
      benefit of lymphocytic infiltration may be explained by the immune destruction of
      budding cells.

PMID- 17516585
TI  - Gain and overexpression of the oncostatin M receptor occur frequently in cervical
      squamous cell carcinoma and are associated with adverse clinical outcome.
AB  - For many oncogenes, increased expression resulting from copy number gain confers
      a selective advantage to cells that consequently make up the tumour bulk. To
      identify oncogenes of potential biological significance in cervical squamous cell
      carcinoma (SCC), 36 primary samples and ten cell lines were screened by array
      comparative genomic hybridization (CGH). The most commonly occurring regions of
      copy number gain that also showed amplification were 5p15.2-14.3 (59%), 5p13.3
      (65%), and 5p13.2-13.1 (63%). Gene copy numbers were significantly associated
      with expression levels for three candidate oncogenes at these loci: OSMR
      (oncostatin M receptor) (p=0.03), PDZK3 (PDZ domain containing protein 3)
      (p=0.04), and TRIO (triple functional domain) (p=0.03). Further examination by
      fluorescence in situ hybridization on a tissue microarray of 110 primary cervical
      SCC samples revealed copy number gain frequencies of 60.9%, 57.3%, and 54.5% for
      OSMR, PDZK3, and TRIO, respectively, with OSMR adversely influencing overall
      patient survival independently of tumour stage (p=0.046). By array CGH, copy
      number gain of OSMR was not seen in any of 40 microdissected precursor cervical
      squamous intraepithelial lesions (SILs). Moreover, global mRNA expression
      analysis, using Affymetrix U133A 2.0 Arrays, showed no overexpression of OSMR in
      SILs, suggesting that OSMR gain and overexpression are relatively late steps in
      cervical carcinogenesis. In the cervical SCC cell lines CaSki and SW756,
      exogenous OSM activated downstream-signalling elements of OSMR including STAT3,
      p44/42 MAPK, and S6 ribosomal protein, and induced transcription of the
      angiogenic factor VEGF, effects that were reduced by OSMR depletion using RNA
      interference. We conclude that copy number gain of OSMR is frequently found in
      cervical SCC and is associated with adverse clinical outcome. As well as being a
      potential prognostic marker, OSMR is a candidate cell surface therapeutic target.

PMID- 17516586
TI  - Characterization of the fraction components using 1D TOCSY and 1D ROESY
      experiments. Four new spirostane saponins from Agave brittoniana Trel. spp.
      Brachypus.
AB  - A careful NMR analysis, especially 1D TOCSY and 1D ROESY, of two refined saponin
      fractions allowed us to determine the structures of four new saponins from a
      polar extract of the Agave brittoniana Trel. spp. Brachypus leaves. A full
      assignment of the 1H and 13C spectral data for these new saponins,
      agabrittonosides A-D (1-4), and one previously known saponin, karatavioside A (5)
      is reported. Their structures were established using a combination of 1D and 2D
      (1H, 1H-COSY, TOCSY, ROESY, g-HSQC, g-HMBC and g-HSQC-TOCSY) NMR techniques and
      ESI-MS. Moreover, the work represents a new approach to structural elucidation of
      saponins in refined fractions by NMR investigations.

PMID- 17516587
TI  - R.B. Merrifield: European footnotes to his life and work.
AB  - Some reflections on the life and work of RB Merrifield in the European context
      are given.

PMID- 17516588
TI  - Tyrosine-heme ligation in heme-peptide complex: design based on conserved motif
      of catalase.
AB  - On the basis of evolutionary conservation of sequence in catalases, we have
      designed a heme-binding peptide (Ac-RLKSYTDTQISR12-(GGGG)-CRIVHC22-NH2) for the
      'redox activity modulation' of heme. Heme-binding studies showed a blue-shifted
      Soret (369 nm) in the presence of TFE and a red-shifted Soret (418 nm) in the
      absence of TFE. These blue- and red-shifted Sorets suggest ligation through
      tyrosinate and histidine, respectively. This is the first designed peptide
      ligating to heme through tyrosine. NMR studies have confirmed that tyrosine
      ligation to heme in this heme-peptide complex occurs only in the presence of TFE.
      We suggest that TFE induces helicity in the peptide and brings the arginine and
      tyrosine in proximity, resulting in ionization of the phenolic side chain of
      tyrosine. In the absence of TFE, the unstructured peptide lacks the intra
      molecular Arg(+)Tyr(-) ion pair, allowing heme binding to histidine. This peptide
      has significant peroxidase activity though it does not have catalase activity.

PMID- 17516589
TI  - Cure rate model with interval censored data.
AB  - In cancer trials, a significant fraction of patients can be cured, that is, the
      disease is completely eliminated, so that it never recurs. In general, treatments
      are developed to both increase the patients' chances of being cured and prolong
      the survival time among non-cured patients. A cure rate model represents a
      combination of cure fraction and survival model, and can be applied to many
      clinical studies over several types of cancer. In this article, the cure rate
      model is considered in the interval censored data composed of two time points,
      which include the event time of interest. Interval censored data commonly occur
      in the studies of diseases that often progress without symptoms, requiring
      clinical evaluation for detection (Encyclopedia of Biostatistics. Wiley: New
      York, 1998; 2090-2095). In our study, an approximate likelihood approach
      suggested by Goetghebeur and Ryan (Biometrics 2000; 56:1139-1144) is used to
      derive the likelihood in interval censored data. In addition, a frailty model is
      introduced to characterize the association between the cure fraction and survival
      model. In particular, the positive association between the cure fraction and the
      survival time is incorporated by imposing a common normal frailty effect. The EM
      algorithm is used to estimate parameters and a multiple imputation based on the
      profile likelihood is adopted for variance estimation. The approach is applied to
      the smoking cessation study in which the event of interest is a smoking relapse
      and several covariates including an intensive care treatment are evaluated to be
      effective for both the occurrence of relapse and the non-smoking duration.

PMID- 17516590
TI  - Quantitative evaluation of the binding of phenylarsenic species to glutathione,
      isotocin, and thioredoxin by means of electrospray ionization time-of-flight mass
      spectrometry.
AB  - An attempt was made to quantitatively describe the binding of phenylarsenic
      species to thiol-containing biomolecules using electrospray ionization mass
      spectrometry (ESI-MS). The extent of the reactions of phenylarsine oxide (PAO)
      with the peptides glutathione and isotocin (ITC) and with the protein thioredoxin
      resulting in covalent As--S bonds were quantified by deriving the dependence of
      the corresponding ion signal intensities on the concentration of the reaction
      products. Problems complicating a quantitative evaluation of the mass spectra,
      such as signal suppression effects, were critically evaluated. Equilibrium
      constants for condensation reactions as well as formation constants for
      noncovalent associations were calculated by means of ESI-MS signal intensities.
      The comparison of the reaction of PAO with different thiol reactants revealed the
      highest binding affinity for ITC followed by thioredoxin and a lower affinity to
      glutathione. Possibly, the intramolecular formation of RS-As(C(6)H(5))-SR
      occurring in case of ITC and thioredoxin is favored over the intermolecular
      product involving two molecules glutathione even though the molecular mass of
      glutathione (307 g mol(-1)) is much smaller than that of ITC (966 g mol(-1)) and
      thioredoxin (11 688 g mol(-1)). A similar binding affinity for trivalent (K
      approximately 1.6 x 10(-3) l micromol(-1)) and pentavalent (K approximately 1.6 x
      10(-3) and 1.0 x 10(-3) l micromol(-1)) arsenic species was found for the
      formation of a noncovalent complex of glutathione with different phenylarsenic
      compounds.

PMID- 17516591
TI  - Proteomics strategy based on liquid-phase IEF and 2-D DIGE: application to bone
      marrow mesenchymal progenitor cells.
AB  - Global comparative proteomics is a promising new approach with broad application
      in basic and clinical biological science. Recent advances include the development
      of 2-D DIGE, a proteomic equivalent to mRNA differential display, in which
      differentially labeled samples are multiplexed and analyzed by high-resolution 2
      DE. This study presents a new 2-D DIGE protocol, in which complex protein samples
      from normal and leukemic human bone marrow mesenchymal progenitor cells were used
      as model samples for a novel combination of liquid-phase IEF with 2-D DIGE. Using
      liquid-phase IEF, the normal and leukemic cells were pre-fractionated into five
      subproteomes after multiplexing but prior to DIGE. Under these conditions, 2-D
      DIGE resolved >5000 protein-containing spots within the pH range 4.6-7.0.
      Differential labeling combined with subsequent MALDI-MS/MS identified proteins
      that were differentially expressed in leukemic cells. This analysis mapped
      protein identities to 128 mesenchymal progenitor cell proteins with at least one
      unique peptide match at >95% confidence. Of these proteins, 72 (56%) were
      expressed more than 1.25-fold higher or lower in leukemic cells compared with
      normal cells (p<0.05). These data were used to infer gene ontology biological
      processes that may be altered in leukemic bone marrow mesenchymal progenitor
      cells.

PMID- 17516592
TI  - Biological soft materials.
AB  - With one or two exceptions, biological materials are "soft", meaning that they
      combine viscous and elastic elements. This mechanical behavior results from self
      assembled supramolecular structures that are stabilized by noncovalent
      interactions. It is an ongoing and profound challenge to understand the self
      organization of biological materials. In many cases, concepts can be imported
      from soft-matter physics and chemistry, which have traditionally focused on
      materials such as colloids, polymers, surfactants, and liquid crystals. Using
      these ideas, it is possible to gain a new perspective on phenomena as diverse as
      DNA condensation, protein and peptide fibrillization, lipid partitioning in
      rafts, vesicle fusion and budding, and others, as discussed in this selective
      review of recent highlights from the literature.

PMID- 17516593
TI  - A highly enantiomerically enriched lithiosilane by selective cleavage of a
      silicon-phenyl bond with lithium.

PMID- 17516594
TI  - A 1,8-naphthylene-bridged bis(indenyl)zinc THF adduct: formation and structure of
      an ansa-zincocene derivative.

PMID- 17516595
TI  - Microfluidic glass chips with an integrated nanospray emitter for coupling to a
      mass spectrometer.

PMID- 17516596
TI  - Phloroglucinol derivatives guttiferone G, aristoforin, and hyperforin: inhibitors
      of human sirtuins SIRT1 and SIRT2.

PMID- 17516597
TI  - One-pot synthesis of manganese oxide nanosheets in aqueous solution: chelation
      mediated parallel control of reaction and morphology.

PMID- 17516598
TI  - Covalently functionalized cobalt nanoparticles as a platform for magnetic
      separations in organic synthesis.

PMID- 17516599
TI  - Mesoporous organic-inorganic hybrid materials built using polyhedral oligomeric
      silsesquioxane blocks.

PMID- 17516600
TI  - The chemical mechanism of D-1-deoxyxylulose-5-phosphate reductoisomerase from
      Escherichia coli.

PMID- 17516601
TI  - Tetraarylphosphonium salts as soluble supports for the synthesis of small
      molecules.

PMID- 17516602
TI  - Diphenylprolinol silyl ether as a catalyst in an enantioselective, catalytic,
      tandem Michael/Henry reaction for the control of four stereocenters.

PMID- 17516603
TI  - Suzuki polycondensation put to work: a tough poly(meta-phenylene) with a high
      glass-transition temperature.

PMID- 17516604
TI  - Synthesis of 1,3,4-trisubstituted isoquinolines by iodine-mediated electrophilic
      cyclization of 2-alkynyl benzyl azides.

PMID- 17516605
TI  - To be dinuclear or not: Z-DNA induction by nickel complexes.
AB  - The left-handed Z-DNA has been identified as a gene regulating element. Therefore
      the generation of Z-DNA through metal complexes might be an innovative way for
      the regulation of gene expression. Use of the new dinuclear complex N,N,N',N'
      tetrakis-[2-(3,5-dimethylpyrazol-1-yl)ethyl]-1,3-propylenediamine-bis(nickel(II)
      dinitrate) (2) reversibly induced Z-DNA formation. However, when a 1:1 ratio of
      metal/dinucleating ligand was used as a control, the midpoint of the B- to Z-DNA
      transition was at the same nickel concentration as in case of the dinuclear
      complex. The novel mononuclear analogue, N-methyl-N,N-bis-[2-(3,5-dimethylpyrazol
      1-yl)ethyl]amine-nickel(II)-dinitrate (3) was inducing the Z-DNA at a similar
      ratio versus nucleotides as free nickel(II) itself. For the first time, proton
      and nickel binding constants for the bis-[2-(pyrazol-1-yl)ethyl]amine ligand
      system are reported and discussed. Both nickel complexes 2 and 3 were
      structurally characterized by single crystal analysis. Furthermore, the synthesis
      of the two new ligands, N,N,N',N'-tetrakis-[2-(3,5-dimethylpyrazol-1-yl)ethyl]
      1,2-propylenediamine (4) and N-methyl-N,N-bis-[2-(3,5-dimethylpyrazol-1
      yl)ethyl]amine (5) is described. The two major synthetic pathways leading to
      polypyrazoyl amines in general are critically discussed with respect to yield,
      reproducibility and handling of the intermediates.

PMID- 17516606
TI  - How important is molecular rigidity for the complex stability of artificial host
      guest systems? A theoretical study on self-assembly of gas-phase arginine.
AB  - Arginine forms much less stable dimers than 2-(guanidiniocarbonyl)-1H-pyrrole-5
      carboxylate although the principal binding interactions are very similar. The
      reasons for this difference are addressed in this work by state-of-the-art ab
      initio computations. The investigation shows that the extraordinary high
      stability of the 2-(guanidiniocarbonyl)-1H-pyrrole-5-carboxylate dimer results to
      about 50 % from the rigidity of its monomer. Within this study monomer and dimer
      conformers of arginine were calculated leading to new low lying structures which
      have not been reported before as well as new global minima are predicted. In
      these structures stacking interactions with the guanidinium moiety are especially
      important. For the monomer we predict the energy minimum to be the canonical form
      with the lowest lying zwitterionic structure being only 9 kJ mol(-1) less stable.
      During the course of these calculations we found that DFT did not predict the
      structures and their relative energy correctly in comparison to perturbation
      theory (MP2) and some potential reasons for the failure of DFT in these cases are
      discussed. Vibrational frequencies of the various structures are presented and a
      suitable wavenumber region for an experimental determination of the global
      minimum of the arginine monomer is identified. The effect of molecular rigidity
      on the self-assembly is probed using a local minimum of the arginine monomer
      which does not possess any intramolecular stabilizing effects. Our results
      suggest that the deliberate control of the conformational flexibility is a
      powerful instrument to steer the complex affinity of artificial hosts.

PMID- 17516607
TI  - Synthesis of a peptide-linked chlorin dyad as a model compound for the
      photosynthetic reaction centre.
AB  - The enantiomerically pure chlorins 19 and 21 were synthesised from tripyrrolic
      nickel complex rac-17 and pyrrole building blocks 12 and 16. The pyrroles are
      annelated with norbornane moieties which contain the chiral information as well
      as two different functionalities. The functional groups, namely a carboxylic acid
      ester and a carbonitrile group, of chlorin 21 finally allowed the formation of an
      amino acid functionality at the periphery of the macrotetracycle. By using
      principles of peptide chemistry, the two chlorin subunits were joined to form the
      peptide-linked chlorin-chlorin dyad 24, which mimics the molecular parts of the
      natural photosynthetic reaction centre.

PMID- 17516608
TI  - Highly reduced, polyoxo(alkoxo)vanadium(III/IV) clusters.
AB  - A family of high nuclearity oxo(alkoxo)vanadium clusters in unprecedentedly low
      oxidation states is reported, synthesised from simple vanadium diketonate
      precursors in alcohols under solvothermal conditions. Crystal structures of
      [V18(O)12(OH)2(H2O)4(EtO)22(O2CPh)6(acac)2] (1),
      [V16Na2(O)18(EtO)16(EtOH)2(O2CPh)6(HO2CPh)2]infinity (2),
      [V13(O)13(EtO)15(EtOH)(RCO2)3] in which R=adamantyl (3) or Ph3C (4), and
      [V11(O)12(EtO)13(EtOH)(Ph3CCO2)2(MePO3)] (5) are reported, revealing these to be
      {VIII 16VIV 2} (1), {VIII 9VIV 3VV} (3 and 4) and {VIII 3VIV 8} (5) clusters,
      while 2 consists of isolated {VIII 8VIV 8} clusters bridged into polymeric chains
      by {Na2(OEt)2} fragments. Solvothermal conditions are essential to the formation
      of these species, and the level of oxidation of the isolated clusters is in part
      controlled by the crystallisation time, with the lowest mean-oxidation-state
      species being isolated by direct crystallisation on controlled cooling of the
      reaction solutions.

PMID- 17516609
TI  - Can [M(H)2(H2)(PXP)] pincer complexes (M=Fe, Ru, Os; X=N, O, S) serve as catalyst
      lead structures for NH3 synthesis from N2 and H2?
AB  - The potential of pincer complexes [M(H)(2)(H(2))(PXP)] (M=Fe, Ru, Os; X=N, O, S)
      to coordinate, activate, and thus catalyze the reaction of N(2) with classical or
      nonclassical hydrogen centers present at the metal center, with the aim of
      forming NH(3) with H(2) as the only other reagent, was explored by means of DF
      (density functional) calculations. Screening of various complexes for their
      ability to perform initial hydrogen transfer to coordinated N(2) showed ruthenium
      pincer complexes to be more promising than the corresponding iron and osmium
      analogues. The ligand backbone influences the reaction dramatically: the presence
      of pyridine and thioether groups as backbones in the ligand result in inactive
      catalysts, whereas ether groups such as gamma-pyran and furan enable the reaction
      and result in unprecedented low activation barriers (23.7 and 22.1 kcal mol(-1),
      respectively), low enough to be interesting for practical application. Catalytic
      cycles were calculated for [Ru(H)(2)(H(2))(POP)] catalysts (POP=2,5
      bis(dimethylphosphanylmethyl)furan and 2,6-bis(dimethylphosphanylmethyl)-gamma
      pyran). The height of activation barriers for the furan system is somewhat more
      advantageous. Formation of inactive metal nitrides has not been observed. SCRF
      calculations were used to introduce solvent (toluene) effects. The Gibbs free
      energies of activation of the numerous single reaction steps do not change
      significantly when solvent is included. The reaction steps associated with the
      formation of the active catalyst from precursors [M(H)(2)(H(2))(PXP)] were also
      calculated. The otherwise inactive pyridine ligand system allows for the
      generation of the active catalyst species, whereas the ether ligand systems show
      activation barriers that could prohibit practical application. Consequently the
      generation of the active catalyst species needs to be addressed in further
      studies.

PMID- 17516610
TI  - The total synthesis and biological properties of the cytotoxic macrolide FD-891
      and its non-natural (Z)-C12 isomer.
AB  - A total, stereoselective synthesis of the naturally occurring, cytotoxic
      macrolide FD-891 and of its non-natural (Z)-C12 isomer is described. Three
      fragments of the main carbon chain were stereoselectively prepared by using
      asymmetric aldol and allylation reactions as the key steps. The molecule was then
      assembled by using two Julia-Kocienski olefinations to connect the three
      fragments and a Yamaguchi reaction to close the macrolactone ring. Some specific
      biological properties (cytotoxicity, binding to tubulin) have been determined for
      both macrolides. The E configuration of the C12-C13 olefinic bond seems to be an
      important feature in determining the cytotoxicity but the precise biological
      mechanism of the latter still remains to be cleared.

PMID- 17516611
TI  - Racemization of secondary alcohols catalyzed by cyclopentadienylruthenium
      complexes: evidence for an alkoxide pathway by fast beta-hydride elimination
      readdition.
AB  - The racemization of sec-alcohols catalyzed by pentaphenylcyclopentadienyl
      ruthenium complex 3a has been investigated. The mechanism involves ruthenium
      alkoxide intermediates: reaction of tert-butoxide ruthenium complex 4 with a
      series of sec-alcohols with different electronic properties gave ruthenium
      complexes bearing a secondary alkoxide as a ligand. The characterization of these
      alkoxide complexes by NMR spectroscopy together with a study of the reaction
      using in situ IR spectroscopy is consistent with a mechanism in which the
      alkoxide substitution step and the beta-hydride elimination step occur without CO
      dissociation. The alkoxide substitution reaction is proposed to begin with
      hydrogen bonding of the incoming alcohol to the active ruthenium-alkoxide
      intermediate. Subsequent alkoxide exchange can occur via two pathways: i) an
      associative pathway involving a eta3-CpRu intermediate; or ii) a dissociative
      pathway within the solvent cage. Racemization at room temperature of a 1:1
      mixture of (S)-1-phenylethanol and (S)-1-phenyl-[D4]-ethanol gave only rac-1
      phenylethanol, and rac-1-phenyl-[D4]-ethanol, providing strong support for a
      mechanism in which the substrate stays coordinated to the metal center throughout
      the racemization, and does not leave the coordination sphere. Furthermore,
      racemization of a sec-alcohol bearing a ketone moiety within the same molecule
      does not result in any reduction of the original ketone, which rules out a
      mechanism where the intermediate ketone is trapped within the solvent cage. These
      results are consistent with a mechanism where eta3-Ph(5)C(5)-ruthenium
      intermediates are involved. Competitive racemization on nondeuterated and alpha
      deuterated alpha-phenylethanols was used to determine the kinetic isotope effect
      kH/kD for the ruthenium-catalyzed racemization. The kinetic isotope effect kH/kD
      for p- X-C(6)H(4)CH(OH)CH(3) was 1.08, 1.27 and 1.45 for X=OMe, H, and CF3,
      respectively.

PMID- 17516612
TI  - Efficient tandem process for the catalytic deprotection of N-allyl amides and
      lactams in aqueous media: a novel application of the bis(allyl)-ruthenium(IV)
      catalysts [Ru(eta3:eta2:eta3-C12H18)Cl2] and [{Ru(eta3:eta3-C10H16)(micro
      Cl)Cl}2].
AB  - An operationally simple and highly efficient methodology for the removal of the
      allyl protecting group in amides and lactams has been developed by using the
      commercially available bis(allyl)-ruthenium(IV) catalysts
      [Ru(eta(3):eta(2):eta(3)-C(12)H(18))Cl(2)] (C(12)H(18)=dodeca-2,6,10-triene-1,12
      diyl) and [{Ru(eta(3):eta(3)-C(10)H(16))(micro-Cl)Cl}(2)] (C(10)H(16)=2,7
      dimethylocta-2,6-diene-1,8-diyl). The tandem process, which takes place in
      aqueous media and proceeds in a one-pot manner, involves the initial
      isomerization of the C=C bond of the allyl unit and subsequent oxidative cleavage
      of the resulting enamide.

PMID- 17516613
TI  - Ionic liquids for soft functional materials with carbon nanotubes.
AB  - A serendipitous finding that ionic liquids gel with carbon nanotubes has opened a
      new possibility of ionic liquids as modifiers for carbon nanotubes. Upon being
      ground into ionic liquids, carbon nanotube bundles are untangled, and the
      resultant fine bundles form a network structure. This is due to the possible
      specific interaction between the imidazolium ion component and the pi-electronic
      nanotube surface. The resultant gelatinous materials, consisting of highly
      electroconductive nanowires and fluid electrolytes, can be utilized for a wide
      variety of electrochemical applications, such as sensors, capacitors, and
      actuators. Ionic liquids allow for noncovalent and covalent modifications of
      carbon nanotubes and fabrication of polymer composites with enhanced physical
      properties. The processing of carbon nanotubes with ionic liquids is not
      accompanied by the disruption of the pi-conjugated nanotube structure and does
      not require solvents; therefore it can readily be scaled up. This article focuses
      on new aspects of ionic liquids for designer soft materials based on carbon
      nanotubes.

PMID- 17516614
TI  - Increased Fas and Bcl-2 expression on peripheral mononuclear cells from patients
      with active juvenile-onset systemic lupus erythematosus.
AB  - OBJECTIVE: To determine expressions of Fas and Bcl-2 on peripheral blood T and B
      lymphocytes from patients with juvenile-onset systemic lupus erythematosus
      (JSLE). METHODS: Thirty-eight patients with JSLE and 21 healthy controls were
      studied. Eleven JSLE patients with SLEDAI score >or= 8 were categorized as
      active. Freshly isolated peripheral blood mononuclear cells were stained for
      lymphocyte markers CD3, CD4, CD8, and CD19 and for Fas and Bcl-2 molecules. Cell
      protein expression was measured by 3-color flow cytometry. RESULTS: Percentages
      of lymphocytes positively stained for Fas antigen and cytoplasmic expression of
      Bcl-2 measured by mean fluorescence intensity from patients were significantly
      increased compared to controls on CD3+, CD4+, and CD8+ T cells. Patients with
      active disease had higher percentages of CD19+ B cells positive for Fas antigen
      compared to patients with inactive lupus. A direct statistical correlation was
      observed between Fas and Bcl-2 expression on CD19+ B cells and SLE Disease
      Activity Index score. CONCLUSION: Patients with juvenile-onset SLE show
      upregulation of apoptosis-related proteins. Patients with active and inactive
      disease have a different profile of Fas and Bcl-2 expression.

PMID- 17516615
TI  - Therapy with immunosuppressive drugs and biological agents and use of
      contraception in patients with rheumatic disease.
AB  - OBJECTIVE: To investigate the attitude of patients towards immunosuppressive and
      biological drugs in relation to reproduction and the outcome of pregnancies
      exposed to these drugs. METHODS: We performed 2 postal surveys in regard to
      immunosuppressive drugs and reproduction, one in patients with rheumatic disease,
      the second in Swiss rheumatologists. RESULTS: Among the 237 female patients and
      the 189 male patients contacted for the survey, 72% of women and 40% of men
      returned the questionnaire. Ninety-four women and 47 men had received one or
      several immunosuppressive or biological agents during the years 2000-2005.
      Correct advice in regard to drugs and necessary birth control had been given to
      84% of women. Advice to men was more inconsistent. One-third of women and 50% of
      men treated with potentially teratogenic drugs methotrexate (MTX) or leflunomide
      had not practiced birth control. The surveys of rheumatologists and patients
      disclosed 66 pregnancies under therapy with immunosuppressive and biological
      drugs with successful outcomes in 73%. However, 20% of pregnancies in women
      occurred under treatment with MTX and leflunomide. CONCLUSION: Issues regarding
      drugs and reproduction are not always sufficiently discussed with female and male
      patients. The increasing use of combination therapies containing MTX necessitates
      ensuring that advice regarding birth control is followed in order to avoid
      pregnancies exposed to potentially fetotoxic drugs.

PMID- 17516616
TI  - Influence of an interactive joint model injection workshop on physicians'
      musculoskeletal procedural skills.
AB  - OBJECTIVE: To assess the effect of an intervention workshop designed to improve
      intraarticular (IA) and periarticular (PA) injection skills among primary care
      physicians. METHODS: An interactive joint model injection workshop was designed
      for family practice and internal medicine residents and faculty, aimed at
      improving their skill performing IA and PA procedures. The workshop covered
      indications, contraindications, complications and supplies required to perform
      procedures, formulations of steroidal preparations, volumes used for injection,
      skin preparation, method of needle insertion, synovial fluid aspirations,
      aftercare, and processing of the synovial fluid. Interactive prewired models of
      shoulders, wrist, hand, knee, ankle, and foot provided feedback with an audible
      buzz for correctly performed procedure. A survey was administered immediately
      following the workshop and after 10 months. RESULTS: Of 60 participants, 39% were
      residents and 21% faculty. The mean age (+/- SD) of participants was 32.7 +/- 7.7
      years. The mean duration of followup was 10.5 months. The mean +/- SD comfort
      scores on theoretical and practical aspects of the procedures surveyed prior to
      the workshop were 4.8 +/- 2.5 and 4.4 +/- 2.5, respectively; and after the
      workshop were 8.0 +/- 1.7 (p = 0.001) and 7.8 +/- 1.7 (p = 0.001), respectively.
      The mean change in comfort scores in practical aspects of IA and PA procedures
      did not correlate with the age of participants, but rather with their
      training/faculty status (p = 0.01). The mean changes in comfort scores with
      practical aspects of these procedures were highest among first-year residents
      (4.5+/- 2.1), followed by faculty (3.1 +/- 1.7). On followup, the mean comfort
      scores on theoretical and practical aspects of the procedures were 6.3 +/- 1.7
      and 6.0 +/- 1.8, respectively, significantly higher than the pre-workshop scores
      (p = 0.03, p = 0.02). CONCLUSION: Joint injection workshops using interactive
      joint models can improve the comfort scores of physicians learning IA and PA
      injection skills, in both theoretical and practical aspects of the procedure.
      Faculty and first-year residents in training seem to benefit the most;
      significant improvement in comfort scores was seen across the spectrum of
      physicians. Thus acquired comfort with knowledge and practical aspects of joint
      procedures may undergo attrition over time; however, significant residual
      benefits are still appreciable over time.

PMID- 17516617
TI  - Articular damage is associated with intraosseous inflammation in the subchondral
      bone marrow of joints affected by experimental inflammatory arthritis and is
      modified by zoledronate treatment.
AB  - OBJECTIVE: We studied histological changes in the cell populations of subchondral
      bone marrow resulting from inflammation in animal models of arthritis.
      Inflammation in intraosseous spaces and the effect of treatment with the
      aminobisphosphonate zoledronate were assessed. METHODS: Peripheral blood, femoral
      bone marrow, and spleen cells were harvested from carrageenan-induced arthritis
      Sprague-Dawley rats; fluorescence stained for CD3, CD8, CD4, CD11b/c, anti
      mononuclear phagocyte (MNP), CD3/CD8, CD3/CD4, and MNP/CD11b/c; and evaluated by
      flow cytometry. Arthritis was induced in New Zealand white rabbits in 5 treatment
      groups: normal, arthritis, zoledronate-treated from arthritis induction, or 2 or
      4 weeks after induction. Animals were euthanized after 7 weeks and distal femoral
      condyles were decalcified, processed, sectioned, and stained. Sections were
      evaluated for several cell types and histological features relevant to
      inflammation, which were assigned a categorical grade from 0 (healthy morphology)
      to 3 (extensive inflammation). Tidemark was evaluated on a continuous scale.
      RESULTS: Significantly elevated levels of CD3+CD4+ lymphocytes and CD11b/c+MNP+
      monocytes were observed in the bone marrow of arthritic rats, consistent with
      intraosseous inflammation. No corresponding increase was observed in peripheral
      blood or spleen. In rabbits, the histology of lymphocytes, mononuclear cells,
      fibrocytes, fibrosis, lipocytes, and plasma cells varied significantly across
      treatment groups. Controls exhibited normal histology. In arthritis, these cell
      types and tissues displayed a shift of 1-2 grades higher (toward inflammation).
      Intact tidemark was reduced. Following zoledronate treatment, mononuclear cells,
      fibrocytes, fibrosis, and lipocytes were significantly altered toward normal, and
      tidemark shifted toward normal. CONCLUSION: Intraosseous bone marrow inflammation
      was observed in carrageenan-induced inflammatory arthritis in rats and rabbits.
      Zoledronate administration diminished the intraosseous inflammatory response.

PMID- 17516618
TI  - The burden of prevalent fractures on health-related quality of life in
      postmenopausal women with osteoporosis: the IMOF study.
AB  - OBJECTIVE: Vertebral fractures are a common complication of osteoporosis and may
      have a negative effect on health-related quality of life (HRQOL). We investigated
      the effect of prevalent vertebral fractures on HRQOL in patients with
      osteoporosis. METHODS: A cross-sectional multicenter study was carried out among
      postmenopausal women with primary osteoporosis attending primary care centers and
      hospital outpatient clinics: 234 women with vertebral fractures and 244
      asymptomatic women. Women with secondary osteoporosis or taking medications that
      affect bone metabolism were excluded. All patients were questioned using the mini
      Osteoporosis Quality of Life Questionnaire (mini-OQLQ), Medical Outcomes Study
      Short Form-36 (SF-36), and the EuroQuol-5D, after assessment of all clinical
      variables and anthropometric data. To assess comorbidity we used the Self
      Administered Comorbidity Questionnaire (SCQ). Diagnosis of osteoporosis was
      confirmed in all patients by bone mineral density using dual energy x-ray
      absorptiometry. Radiographic evaluation was performed by a musculoskeletal
      radiologist. A total of 483 postmenopausal women, randomly matched for age out of
      1579 healthy controls, were chosen to compare the SF-36 scores with respect to
      patients with and without vertebral fractures due to osteoporosis. A
      multivariable regression analysis was conducted to identify the strongest
      determinant for low HRQOL, adjusted for potential confounding variables such as
      comorbid conditions, education level, and psychosocial status. RESULTS: The
      vertebral fracture group had significantly lower scores than patients without
      fractures and controls in all domains of the generic and specific questionnaires.
      Women with only 1 prevalent fracture had statistically significantly lower HRQOL
      scores than those without fractures on SF-36 measures of bodily pain, physical
      functioning, and role function physical (all p < 0.01). HRQOL scores were lower
      in women with lumbar fractures compared with women with thoracic fractures only
      when the physical functioning and bodily pain dimensions approached statistical
      significance. Based on the multivariate analysis, the strongest determinant for
      low HRQOL was physical functioning (explained by number of vertebral fractures)
      followed by comorbidity score and age. Adjusted R2 in the final model was 35.9%.
      Using the SF-36 summary scales, comorbid conditions predominantly affected either
      mental or physical health (p < 0.0001). A significant correlation (p <0.0001) was
      found between total score on the mini-OQLQ and the mean SCQ comorbidity score.
      CONCLUSION: Our results confirm previous findings that HRQOL, assessed by generic
      and osteoporosis-specific instruments, is decreased in patients with vertebral
      fractures due to osteoporosis as a function of the number of vertebral fractures,
      presence of comorbid conditions, and age.

PMID- 17516619
TI  - Inhibition of alkaline phosphatase by cysteine: implications for calcium
      pyrophosphate dihydrate crystal deposition disease.
AB  - OBJECTIVE: Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, a
      common arthritis affecting the elderly, is characterized by the deposition of
      CPPD crystals in articular joints. The mechanism underlying disease expression is
      unknown, but factors contributing to the pathogenesis may involve changes in
      enzymatic activities involving pyrophosphate and phosphate metabolism. Tissue
      nonspecific alkaline phosphatase (TNAP) is one of the major enzymes regulating
      pyrophosphate concentrations in articular joints. We hypothesized that inhibition
      of TNAP activity at pH = 7.4 by endogenous molecules can lead to CPPD disease
      pathogenesis. METHODS: We investigated the inhibitory effects of the amino acid
      cysteine on TNAP's phosphatase, inorganic pyrophosphatase, and CPPD crystal
      dissolution activities. Kinetic parameters V(max), K(M), concentration for 50%
      inhibition (I(50)), inhibitor constant (K(I)), and specific activities calculated
      from Initial Velocity, Eadie-Hofstee, Simple, Dixon, and Secondary plots were
      used to assess enzyme inhibition. RESULTS: Cysteine inhibited TNAP's phosphatase
      activity uncompetitively and its inorganic pyrophosphatase activity mix
      competitively. CPPD crystal dissolution activity was also inhibited. I(50) values
      demonstrated that high cysteine concentration is required to inhibit 50% of
      enzyme activity. K(I) values suggested that inorganic pyrophosphatase activity is
      inhibited more than the phosphatase activity. Ca(++) and Mg(++) ion
      concentrations may regulate this inhibition. CONCLUSION: The control of
      endogenous inhibitors, such as cysteine, that interfere with TNAP's ability to
      regulate CPPD crystal formation and dissolution in joints could be a potential
      therapeutic option for CPPD crystal deposition disease.

PMID- 17516620
TI  - A pilot study of tumor necrosis factor inhibition in erosive/inflammatory
      osteoarthritis of the hands.
AB  - OBJECTIVE: To determine if anti-tumor necrosis factor (TNF) therapy (adalimumab)
      can safely improve symptoms of erosive/inflammatory osteoarthritis (EOA).
      METHODS: This was an open-label pilot trial in 12 patients with EOA. Patients >
      45 years old with EOA of the hands defined by > or = 2 tender and > or = 2
      swollen joints (distal interphalangeal, proximal interphalangeal, first
      carpometacarpal) despite nonsteroidal antiinflammatory drug therapy were
      eligible. Patients were excluded for autoimmune arthritis, recent disease
      modifying antirheumatic drug use, prior use of anti-TNF therapy, infection,
      malignancy, or poorly controlled medical conditions. All patients received
      adalimumab 40 mg every other week for 12 weeks. Safety was assessed 4 weeks after
      the final dose. Primary endpoints included safety and American College of
      Rheumatology (ACR) response. RESULTS: Patients were predominantly female with a
      mean age of 60 years and 12 years of arthritis. All patients completed the study
      and safety followup. Adverse events were mild without necessitating
      discontinuation of study drug. After 12 weeks, there was a statistically
      significant improvement in the number of swollen joints compared to baseline (p <
      0.01). One patient achieved an ACR20 response and 42% achieved an OMERACT-OARSI
      response. Although we detected no statistically significant improvement in the
      number of tender joints, grip strength, disability, pain, or global disease
      assessments, trends suggested modest improvement in all efficacy measures.
      CONCLUSION: This small open-label study of patients with EOA demonstrated that
      adalimumab was well tolerated. Treatment with adalimumab for 3 months did not
      significantly improve the signs and symptoms of EOA and most patients did not
      achieve an ACR20. Trends suggested improvement and individual patients had some
      benefit. Factors limiting interpretation of this study include the lack of a
      control group, outcomes chosen, number of patients treated, and the duration of
      treatment.

PMID- 17516621
TI  - Ethnic disparities among patients with pulmonary hypertension associated with
      systemic sclerosis.
AB  - OBJECTIVE: To examine a cohort of patients with systemic sclerosis (SSc) and
      pulmonary hypertension (PH) for ethnic disparities in clinical presentation,
      disease detection, or management. METHODS: Encounters of patients with SSc seen
      at the Medical University of South Carolina were recorded in a computerized
      database from November 1997 through January 2004. Patients were evaluated for
      discrepancy in disease manifestation and treatment. Evaluation criteria included
      patient ethnicity (by self report), age, disease duration from onset of first non
      Raynaud's symptom, presence or absence of PH, incidence of diastolic dysfunction
      and left ventricular hypertrophy among patients with PH, severity of interstitial
      lung disease, and treatment course. RESULTS: African Americans were more likely
      than Caucasians to have diffuse cutaneous SSc (dcSSc) (69.9% vs 42.9%, p < 0.001)
      and they presented with PH (defined as right ventricular systolic pressure > 40
      mm Hg by echocardiogram or mean pulmonary artery pressure > 25 mm Hg by right
      heart catheterization (RHC) at a younger age (60.9 yrs vs 49.0 yrs, p < 0.001).
      There were no ethnic disparities in time from onset of the first non-Raynaud's
      symptom to detection of PH, method of PH detection, or treatment modalities.
      Patients with PH were more likely to have diastolic dysfunction than those
      without PH (52.3% vs 35.9%, p = 0.011). CONCLUSION: In this cohort of patients,
      African Americans were more likely to have dcSSc. Among patients with PH, African
      Americans presented at a younger age than their Caucasian counterparts. Incidence
      of diastolic dysfunction was higher in the PH population. There were no
      significant ethnic disparities in time of progression to PH or in treatment
      modalities employed in our cohort.

PMID- 17516622
TI  - Elevated serum bioactive prolactin concentrations in patients with systemic lupus
      erythematosus are associated with disease activity as disclosed by homologous
      receptor bioassays.
AB  - OBJECTIVE: To assess the bioactivity of circulating prolactin (PRL) in serum
      samples from patients with systemic lupus erythematosus (SLE) using 2 novel
      homologous in vitro bioassays, and to correlate PRL bioactivity with lupus
      activity. METHODS: Serum samples from 98 SLE patients with and without disease
      activity were tested for immunoreactive and bioactive concentrations of PRL.
      RESULTS: Patients with active disease exhibited higher bioactive serum PRL levels
      in homologous bioassays (p <or= 0.013). In contrast, bioactivity in Nb2 cells was
      similar between patients with and without activity. The bioactive/immunoreactive
      PRL ratio (BA/IA) in homologous bioassays was significantly higher in patients
      with both clinical manifestations and serological indicators of lupus disease
      activity. SLE patients with idiopathic hyperprolactinemia (HPRL) and
      macroprolactinemia (MPRL) had low SLEDAI scores, and the BA/IA ratio in
      homologous bioassays was significantly lower compared to those with idiopathic
      HPRL and no MPRL. There was a negative but significant correlation between MPRL
      and BA/IA in homologous bioassays (p < 0.001), but not when the heterologous
      bioassay was employed. CONCLUSION: Elevated serum bioactive PRL levels revealed
      by homologous bioassays were associated with disease activity, as well as with
      specific organ involvement. Big big PRL or macroprolactin is a PRL variant with
      reduced bioactivity towards its homologous receptor, and this altered bioactivity
      may contribute to the lower disease activity and absence of symptoms related to
      HPRL in SLE patients. These novel data must be considered in future studies to
      establish a relationship between PRL and disease activity in SLE.

PMID- 17516623
TI  - Association study of Toll-like receptor 5 (TLR5) and Toll-like receptor 9 (TLR9)
      polymorphisms in systemic lupus erythematosus.
AB  - OBJECTIVE: Toll-like receptors (TLR) play an important role in both adaptive and
      innate immunity. Variations in TLR genes have been shown to be associated with
      various infectious and inflammatory diseases. We investigated the association of
      TLR5 (Arg392Stop, rs5744168) and TLR9 (-1237T-->C, rs5743836) single nucleotide
      polymorphisms (SNP) with systemic lupus erythematosus (SLE) in Caucasian American
      subjects. METHODS: We performed a case-control association study and genotyped
      409 Caucasian women with SLE and 509 Caucasian healthy female controls using
      TaqMan allelic discrimination (rs5744168) or polymerase chain reaction
      restriction fragment length polymorphism analysis (rs5743836). RESULTS: None of
      the 2 TLR SNP showed a statistically significant association with SLE risk in our
      cohort. CONCLUSION: Our results do not indicate a major influence of these
      putative functional TLR SNP on the susceptibility to (or protection from) SLE.

PMID- 17516624
TI  - Quantification of reduced health-related quality of life in patients with
      rheumatoid arthritis compared to the general population.
AB  - OBJECTIVE: To compare levels of health-related quality of life (HRQOL) among
      patients with rheumatoid arthritis (RA) to those of the general population.
      METHODS: Disease burden was assessed using a generic health status instrument
      (Medical Outcome Study Short Form-36) for measurements of HRQOL and SF-6D to
      calculate utility scores in representative patients aged 20 to 79 years from the
      Oslo RA Register (n = 1052), and in individuals in the general population (n =
      2323). Comparisons were performed with respect to sex and age, and standardized
      difference scores (s-scores) were calculated for comparisons with the norm.
      RESULTS: HRQOL in patients with RA was reduced compared to the general population
      on all scales of the SF-36 for both males and females and for all age groups. s
      scores adjusted for age and education ranged from -1.39 for physical functioning
      to -0.27 for mental health. The overall difference in utility was 0.16 and ranged
      from 0.13 (in female patients below 50 yrs) to 0.20 (patients 50-60 years). This
      implies that RA of 1 year duration entails a disease burden of 14-20 quality
      adjusted life-years in 100 RA patients. CONCLUSION: RA inflicts a substantial
      disease burden, and the disease affects all HRQOL dimensions as measured by the
      SF-36 in both sexes and in all age groups. Physical functioning is predominantly
      affected, but RA has social and mental consequences.

PMID- 17516625
TI  - A new, simple method for linking of antibodies to atomic force microscopy tips.
AB  - Functionalization of atomic force microscope (AFM) tips with bioligands converts
      them into monomolecular biosensors which can detect complementary receptor
      molecules on the sample surface. Flexible PEG tethers are preferred because the
      bioligand can freely reorient and locally palpate the sample surface while the
      AFM tip is moved along. In a well-established coupling scheme [Hinterdorfer et
      al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 3477-3481], a heterobifunctional PEG
      linker is used to tether thiol-containing bioligands to amino-functionalized AFM
      tips. Since antibodies contain no free thiol residues, prederivatization with N
      succinimidyl 3-(acetylthio)propionate (SATP) is needed which causes a relatively
      high demand for antibody. The present study offers a convenient alternative with
      minimal protein consumption (e.g., 5 microg of protein in 50 microL of buffer)
      and no prederivatization, using a new heterobifunctional cross-linker that has
      two different amino-reactive functions. One end is an activated carboxyl (N
      hydroxysuccinimide ester) which is much faster to react with the amino groups of
      the tips than the benzaldehyde function on its other end. The reactivity of the
      latter is sufficient, however, to covalently bind lysine residues of proteins via
      Schiff base formation. The method has been critically examined, using
      biotinylated IgG as bioligand on the tip and mica-bound avidin as complementary
      receptor. These experiments were well reproduced on amino-functionalized silicon
      nitride chips where the number of specifically bound IgG molecules (approximately
      2000 per microm2) was estimated from the amount of specifically bound ExtrAvidin
      peroxidase conjugate. For a bioscientific application, human rhinovirus particles
      were tethered to the tip, very-low-density lipoprotein receptor fragments were
      tethered to mica, and the specific interaction was studied by force microscopy.

PMID- 17516626
TI  - Preparation and characterization of functional poly(ethylene glycol) surfaces for
      the use of antibody microarrays.
AB  - Protein microarrays serve as measurement platforms for multianalytical
      applications. Small molecules, DNA, proteins, and cells are determined
      quantitatively. Amino-PEG surfaces can be a smart functional platform for protein
      microarrays with high signal-to-noise ratios. An effective step-by-step chemistry
      is developed for uniform presentation of terminal functional groups at each
      monolayer. Poly(ethelene glycol diamine) 2000 (DAPEG, 2000 g/mol) films were
      prepared onto silanized glass slides presenting epoxy groups. The uniformity of
      the grafted DAPEG monolayer is characterized by a chemiluminescence reaction
      using a chemiluminescence microarray reader with automated reagent supply and a
      horseradish peroxidase (HRP)/luminol reporter system. An intensity line plot on
      the horizontal axis was generated. The chemiluminescence intensities vary in a
      range of 2.6%. Antibodies against HRP as model system were immobilized on N
      hydroxysuccinimide activated DAPEG layers by means of a microcontact roboter
      system. Chemiluminescence signals of bound HRP are detected at each spot with a
      standard deviation of 2.9%. The maximum antibody concentration that can be
      immobilized at the surface is determined with 1 mg/mL. Additives for an optimal
      spotting buffer are also studied. The use of the block-copolymer Pluronic F127 as
      antibody stabilizer is as well investigated as trehalose for the prevention of
      spot evaporation. The lowest detectable HRP concentration is 0.08 ng/mL
      determined on anti-HRP antibody microarrays. This study demonstrates how surfaces
      and analytical parameters for protein microarray applications can be
      characterized with a chemiluminescence readout system using a HRP reporter
      system.

PMID- 17516627
TI  - Role of the extracellular loop in the folding of a CFTR transmembrane helical
      hairpin.
AB  - The folding of membrane-spanning domains into their native functional forms
      depends on interactions between transmembrane (TM) helices joined by covalent
      loops. However, the importance of these covalent linker regions in mediating the
      strength of helix-helix associations has not been systematically addressed. Here
      we examine the potential structural impact of cystic fibrosis-phenotypic
      mutations in the extracellular loop 2 (ECL2) on interactions between the TM3 and
      TM4 helices of the cystic fibrosis transmembrane conductance regulator (CFTR) in
      constructs containing CFTR residues 194-241. When the effects of replacements in
      ECL2 (including the CF-phenotypic mutants E217G and Q220R) were evaluated in a
      library of wild-type and mutant TM3-ECL2-TM4 hairpin constructs, we found that
      SDS-PAGE gel migration rates differed over a range of nearly 40% +/- the wild
      type position and that decreased migration rates correlate with increasing
      hairpin alpha-helical content as measured by circular dichroism spectra in sodium
      dodecyl sulfate micelles. The decreased mobility of TM3/4 constructs by
      introduction of non-native residues is interpreted in terms of an elongation or
      "opening" of the helical hairpin and concomitant destabilization of membrane
      based helix-helix interactions. Our results support a role for short loop regions
      in dictating the stability of membrane protein folds and highlight the interplay
      between membrane-embedded helix-helix interactions and loop conformation in
      influencing the structure of membrane proteins.

PMID- 17516628
TI  - Plasmon waveguide resonance spectroscopic evidence for differential binding of
      oxidized and reduced Rhodobacter capsulatus cytochrome c2 to the cytochrome bc1
      complex mediated by the conformation of the Rieske iron-sulfur protein.
AB  - The dissociation constants for the binding of Rhodobacter capsulatus cytochrome
      c2 and its K93P mutant to the cytochrome bc1 complex embedded in a phospholipid
      bilayer were measured by plasmon waveguide resonance spectroscopy in the presence
      and absence of the inhibitor stigmatellin. The reduced form of cytochrome c2
      strongly binds to reduced cytochrome bc1 (Kd = 0.02 microM) but binds much more
      weakly to the oxidized form (Kd = 3.1 microM). In contrast, oxidized cytochrome
      c2 binds to oxidized cytochrome bc1 in a biphasic fashion with Kd values of 0.11
      and 0.58 microM. Such a biphasic interaction is consistent with binding to two
      separate sites or conformations of oxidized cytochrome c2 and/or cytochrome bc1.
      However, in the presence of stigmatellin, we find that oxidized cytochrome c2
      binds to oxidized cytochrome bc1 in a monophasic fashion with high affinity (Kd =
      0.06 microM) and reduced cytochrome c2 binds less strongly (Kd = 0.11 microM) but
      approximately 30-fold more tightly than in the absence of stigmatellin.
      Structural studies with cytochrome bc1, with and without the inhibitor
      stigmatellin, have led to the proposal that the Rieske protein is mobile, moving
      between the cytochrome b and cytochrome c1 components during turnover. In one
      conformation, the Rieske protein binds near the heme of cytochrome c1, while the
      cytochrome c2 binding site is also near the cytochrome c1 heme but on the
      opposite side from the Rieske site, where cytochrome c2 cannot directly interact
      with Rieske. However, the inhibitor, stigmatellin, freezes the Rieske protein
      iron-sulfur cluster in a conformation proximal to cytochrome b and distal to
      cytochrome c1. We conclude from this that the dual conformation of the Rieske
      protein is primarily responsible for biphasic binding of oxidized cytochrome c2
      to cytochrome c1. This optimizes turnover by maximizing binding of the substrate,
      oxidized cytochrome c2, when the iron-sulfur cluster is proximal to cytochrome b
      and minimizing binding of the product, reduced cytochrome c2, when it is proximal
      to cytochrome c1.

PMID- 17516629
TI  - Continuous nucleocytoplasmic shuttling underlies transcriptional activation of
      PPARgamma by FABP4.
AB  - FABP4 delivers specific ligands from the cytosol to the nuclear receptor
      PPARgamma in the nucleus, thereby facilitating the ligation and enhancing the
      transcriptional activity of the receptor. Here, we delineate the structural
      features that underlie the nucleocytoplasmic transport of FABP4. The primary
      sequence of FABP4 does not harbor a readily identifiable nuclear localization
      signal (NLS). However, such a signal could be found in the three-dimensional
      structure of the protein and was mapped to three basic residues that form a
      functional NLS stabilized by the FABP4/PPARgamma ligand troglitazone. We show
      that FABP4 is also subject to active nuclear export. Similarly to the NLS, the
      nuclear export signal (NES) is not apparent in the primary sequence, but
      assembles in the tertiary structure from three nonadjacent leucine residues to
      form a motif reminiscent of established NES. The data demonstrate that both
      nuclear export and nuclear import are critical for enabling FABP4 to enhance the
      transcriptional activity of PPARgamma. Additionally, the observations provide
      insight into the fundamental question of how proteins are activated by ligands.
      Such an activation may be understood by the "induced-fit" model, which states
      that ligand-induced conformational changes precede activation of a protein.
      Alternatively, the "pre-existing equilibrium" hypothesis postulates that
      activated conformations exist within the repertoire of apoproteins, and that
      ligands do not induce these but merely stabilize them. Studies of the subcellular
      localization of FABP4 support the validity of the "pre-existing equilibrium"
      model for the ligand-controlled activation of the nuclear import of FABP4.

PMID- 17516630
TI  - Dioldehydrase: an essential role for potassium ion in the homolytic cleavage of
      the cobalt-carbon bond in adenosylcobalamin.
AB  - The complex of dioldehydrase with adenosylcobalamin (coenzyme B12) and potassium
      ion reacts with molecular oxygen in the absence of a substrate to oxidize
      coenzyme and inactivate the complex. In this article, high performance liquid
      chromatography and mass spectral analysis are used to identify the nucleoside
      products resulting from oxygen inactivation. The product profile indicates that
      oxygen inactivation proceeds by direct reaction of molecular oxygen with the 5'
      deoxyadenosyl radical and cob(II)alamin. Formation of 5'-peroxyadenosine as the
      initial nucleoside product chemically correlates this reaction with aerobic,
      aqueous photoinduced homolytic cleavage of adenosylcobalamin (Schwartz, P. A.,
      and Frey, P. A., (2007) Biochemistry, in press), indicating that both reactions
      proceed through similar chemical intermediates. The oxygen inactivation of the
      enzyme-coenzyme complex shows an absolute requirement for the same monocations
      required in catalysis by dioldehydrase. Measurements of the dissociation
      constants for adenosylcobalamin from potassium-free (Kd = 16 +/- 2 microM) or
      potassium-bound dioldehydrase (Kd = 0.8 +/- 0.2 microM) reveal that the effect of
      the monocation in stimulating oxygen sensitivity cannot be explained by an effect
      on the binding of coenzyme to the enzyme. Cross-linking experiments suggest that
      the full quaternary structure is assembled in the absence of potassium ion under
      the experimental conditions. The results indicate that dioldehydrase likely
      harvests the binding energy of the activating monocation to stimulate the
      homolytic cleavage of the Co-C5' bond in adenosylcobalamin.

PMID- 17516631
TI  - Domain stability and metal-induced folding of calcium- and integrin-binding
      protein 1.
AB  - It is widely accepted that a pair of EF-hands is the functional unit of typical
      four EF-hand proteins such as calmodulin or troponin C. In this work we
      investigate the structure and stability of the four EF-hand domains in the
      related protein calcium- and integrin-binding protein 1 (CIB1) in the presence
      and absence of Mg2+ or Ca2+, to determine if similar EF-hand interactions occur.
      The backbone structure and flexibility of CIB1 were first studied by NMR
      spectroscopy, and these studies were complimented with steady-state fluorescence
      spectroscopy and chemical denaturation experiments using mutant CIB1 proteins
      having single Trp reporter groups in each of the four EF-hand domains EF-I
      (F34W), EF-II (F91W), EF-III (L128W), and EF-IV (F173W). We find that Mg2+-CIB1
      adopts a well-folded structure similar to Ca2+-CIB1, except for some
      conformational heterogeneity in the C-terminal EF-IV domain. The structure of apo
      CIB1 is significantly more dynamic, especially within EF-II, EF-III, and a
      partially unfolded EF-IV region, but the N-terminal EF-I region of apo-CIB1 has a
      well-ordered and more stable structure. The data reveal significant communication
      between the N- and C-lobes of CIB1, and show that transient intermediate
      conformations are formed along the unfolding pathway for each form of the
      protein. Collectively the data demonstrate that the communication between the
      paired EF-hand domains as well as between the N- and C-lobes of CIB1 is distinct
      from the ancestral proteins calmodulin and troponin C, which might be important
      for the unique function of CIB1 in numerous biological processes.

PMID- 17516633
TI  - Effect of hexafluorobenzene on the photophysics of pyrene.
AB  - Absorption and fluorescence spectroscopy studies reveal the formation of a weak
      complex between pyrene and C(6)F(6) even in very dilute systems. The complex
      affects the photophysics of pyrene and reveals a combination of static and
      dynamic-quenching phenomena in both polar and nonpolar solvents. The results are
      supported by computational studies that shed light on the structure of the
      complex and the interactions involved and suggest that ground and excited-state
      interactions are of comparable magnitude; the association is believed to be
      driven by quadrupolar interactions. Understanding these interactions in solution
      is important for applications that aim at controlling the regio- or
      stereoselectivity of organic reactions.

PMID- 17516632
TI  - Mechanistic and structural analysis of human spermidine/spermine N1
      acetyltransferase.
AB  - The N1-acetylation of spermidine and spermine by spermidine/spermine
      acetyltransferase (SSAT) is a crucial step in the regulation of the cellular
      polyamine levels in eukaryotic cells. Altered polyamine levels are associated
      with a variety of cancers as well as other diseases, and key enzymes in the
      polyamine pathway, including SSAT, are being explored as potential therapeutic
      drug targets. We have expressed and purified human SSAT in Escherichia coli and
      characterized its kinetic and chemical mechanism. Initial velocity and inhibition
      studies support a random sequential mechanism for the enzyme. The bisubstrate
      analogue, N1-spermine-acetyl-coenzyme A, exhibited linear, competitive inhibition
      against both substrates with a true Ki of 6 nM. The pH-activity profile was bell
      shaped, depending on the ionization state of two groups exhibiting apparent pKa
      values of 7.27 and 8.87. The three-dimensional crystal structure of SSAT with
      bound bisubstrate inhibitor was determined at 2.3 A resolution. The structure of
      the SSAT-spermine-acetyl-coenzyme A complex suggested that Tyr140 acts as general
      acid and Glu92, through one or more water molecules, acts as the general base
      during catalysis. On the basis of kinetic properties, pH dependence, and
      structural information, we propose an acid/base-assisted reaction catalyzed by
      SSAT, involving a ternary complex.

PMID- 17516634
TI  - Comment on "Origin of the nonplanarity of tetrafluoro cyclobutadiene, C4F4".

PMID- 17516635
TI  - Oxidation of cyclic dipeptides by photoinduced H-atom abstraction. A laser flash
      FT EPR and optical spectroscopy study.
AB  - Laser flash photolysis with the Fourier transform electron paramagnetic resonance
      (FT EPR) and optical spectroscopy detection methods on the nanosecond time scale
      have been employed in order to investigate the oxidation mechanism of cyclic
      dipeptides glycine, alanine, and sarcosine anhydrides initiated by SO4*- or 9,10
      anthraquinone-2,6-disulfonate (2,6-AQDS) triplet in oxygen free aqueous
      solutions. A direct hydrogen abstraction from the ring C-H position of an
      anhydride by both oxidants is proposed as the primary reaction, rather then an
      electron transfer from nitrogen followed by (alpha)C-H deprotonation. The overall
      second-order rate constants for the reaction with SO4*- were determined to be 7.2
      x 10(7) M(-1) s(-1), 1.2 x 10(8) M(-1) s(-1), and 5.2 x 10(8) M(-1) s(-1) for
      glycine anhydride, alanine anhydride, and sarcosine anhydride, respectively. The
      rate constants for 2,6-AQDS triplet as oxidizing species are about two times
      lower. The radical intermediate products derived from cyclic dipeptides observed
      on the microsecond time scale were assigned to the general structure of
      piperazine-2,5-dione-3-yl radical. These are spin polarized by the mechanisms of
      chemically induced dynamic electron polarization (CIDEP). For SO4*- as the
      oxidant the spectra are exhibiting an E/A* polarization pattern originating
      partially from F-pairs of two piperazine-2,5-dione-3-yl radicals.

PMID- 17516636
TI  - Structural variation of silver clusters from Ag13 to Ag160.
AB  - The structures of silver clusters from Ag(121) to Ag(160) were optimized with a
      modified dynamic lattice searching (DLS) method, named as DLS with constructed
      core (DLSc). The interaction among silver atoms is modeled by the Gupta
      potential. Structural characteristic of silver clusters with the growth of
      cluster size is investigated with the newly optimized structures and our previous
      results from Ag(13) to Ag(120). A set of amorphous structures was obtained in the
      size range of 13-48, together with several ordered structures. The putative
      stable motif is an icosahedron from Ag(49) to Ag(61) and then changes to a
      decahedron in the size range of 62-160. Some of the results are consistent with
      experiments. Furthermore, it was also found that, for clusters with decahedral
      motif, the stable structure is a result of the competition among the different
      Marks decahedral motifs. On the other hand, different from the Lennard-Jones
      cluster, there are some silver clusters with the face-centered cubic (fcc) motif
      in the size range of 13-160. But the fcc motif can only be obtained for some
      specific sizes.

PMID- 17516638
TI  - Crossed molecular beam studies of the reactions of allyl radicals, C3H5(X2A2),
      with methylacetylene (CH3CCH(X1A1)), allene (H2CCCH2(X1A1)), and their
      isotopomers.
AB  - The chemical dynamics of the reaction of allyl radicals, C(3)H(5)(X(2)A(2)), with
      two C(3)H(4) isomers, methylacetylene (CH(3)CCH(X(1)A(1))) and allene
      (H(2)CCCH(2)(X(1)A(1))) together with their (partially) deuterated counterparts,
      were unraveled under single-collision conditions at collision energies of about
      125 kJ mol(-1) utilizing a crossed molecular beam setup. The experiments indicate
      that the reactions are indirect via complex formation and proceed via an addition
      of the allyl radical with its terminal carbon atom to the terminal carbon atom of
      the allene and of methylacetylene (alpha-carbon atom) to form the intermediates
      H(2)CCHCH(2)CH(2)CCH(2) and H(2)CCHCH(2)CHCCH(3), respectively. The lifetimes of
      these intermediates are similar to their rotational periods but too short for a
      complete energy randomization to occur. Experiments with D4-allene and D4
      methylacetylene verify explicitly that the allyl group stays intact: no hydrogen
      emission was observed but only the release of deuterium atoms from the
      perdeuterated reactants. Further isotopic substitution experiments with D3
      methylacetylene combined with the nonstatistical nature of the reaction suggest
      that the intermediates decompose via hydrogen atom elimination to 1,3,5
      hexatriene, H(2)CCHCH(2)CHCCH(2), and 1-hexen-4-yne, H(2)CCHCH(2)CCCH(3),
      respectively, via tight exit transition states located about 10-15 kJ mol(-1)
      above the separated products. The overall reactions were found to be endoergic by
      98 +/- 4 kJ mol(-1) and have characteristic threshold energies to reaction
      between 105 and 110 kJ mol(-1). Implications of these findings to combustion and
      interstellar chemistry are discussed.

PMID- 17516640
TI  - Systematic analysis of enzyme-catalyzed reaction patterns and prediction of
      microbial biodegradation pathways.
AB  - The roles of chemical compounds in biological systems are now systematically
      analyzed by high-throughput experimental technologies. To automate the processing
      and interpretation of large-scale data it is necessary to develop bioinformatics
      methods to extract information from the chemical structures of these small
      molecules by considering the interactions and reactions involving proteins and
      other biological macromolecules. Here we focus on metabolic compounds and present
      a knowledge-based approach for understanding reactivity and metabolic fate in
      enzyme-catalyzed reactions in a given organism or group. We first constructed the
      KEGG RPAIR database containing chemical structure alignments and structure
      transformation patterns, called RDM patterns, for 7091 reactant pairs (substrate
      product pairs) in 5734 known enzyme-catalyzed reactions. A total of 2205 RDM
      patterns were then categorized based on the KEGG PATHWAY database. The majority
      of RDM patterns were uniquely or preferentially found in specific classes of
      pathways, although some RDM patterns, such as those involving phosphorylation,
      were ubiquitous. The xenobiotics biodegradation pathways contained the most
      distinct RDM patterns, and we developed a scheme for predicting bacterial
      biodegradation pathways given chemical structures of, for example, environmental
      compounds.

PMID- 17516639
TI  - Design, synthesis, and biological evaluation of novel bifunctional C-terminal
      modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor
      antagonists.
AB  - A series of bifunctional peptides that act as agonists for delta and mu opioid
      receptors with delta selectivity and as antagonist for neurokinin-1 (NK1)
      receptors were designed and synthesized for potential application as analgesics
      in various pain states. The peptides were characterized using radioligand binding
      assays and functional assays using cell membrane and animal tissue. Optimization
      was performed on the fifth residue which serves as an address moiety for both
      receptor recognitions. It had critical effects on both activities at delta/mu
      opioid receptors and NK1 receptors. Among the synthesized peptides, H-Tyr-D-Ala
      Gly-Phe-Met-Pro-Leu-Trp-O-3,5-Bzl(CF3) 2 (5) and H-Tyr-D-Ala-Gly-Phe-Nle-Pro-Leu
      Trp-O-3,5-Bzl(CF3)2 (7) had excellent agonist activity for both delta opioid and
      mu opioid receptors and excellent antagonist activity for NK1 receptors. These
      results indicate that the rational design of multifunctional ligands with opioid
      agonist and neurokinin-1 antagonist activities can be accomplished and may
      provide a new tool for treatment of chronic and several pain states.

PMID- 17516641
TI  - Neutral hexa- and pentacoordinate silicon(IV) complexes with SiO(6) and SiO(4)N
      skeletons.
AB  - The neutral heteroleptic hexacoordinate silicon(IV) complexes 4 and 5 (SiO(6)
      skeletons) and the neutral pentacoordinate silicon(IV) complexes 7-9 (SiO(4)N
      skeletons) were synthesized, starting from the hexacoordinate precursor 2 and the
      pentacoordinate precursor 6, respectively. In these reactions, two monoanionic
      cyanato-N ligands are replaced by one dianionic bidentate O,O-chelate ligand.
      Compounds 4, 5, and 7-9 were characterized by single-crystal X-ray diffraction
      and solid-state and solution NMR spectroscopy. The chiral silicon(IV) complexes
      4, 5, 7, and 8 were obtained as racemic mixtures, whereas 9 was isolated as a
      cocrystallizate consisting of the two diastereomers, (C,S)-9 and (A,S)-9 (ratio
      1:1). The stereodynamics of 5 and 8 were studied by variable-temperature (1)H NMR
      experiments.

PMID- 17516642
TI  - Investigation of the intracellular delivery of fluoresceinated peptides by a host
      [2]rotaxane.
AB  - The development of methods to transport peptides into cells via a passive
      mechanism would greatly aid in the development of therapeutic agents. We recently
      demonstrated that an impermeable fluoresceinated pentapeptide enters the
      cytoplasm and nucleus of COS 7 cells in the presence of a host-[2]rotaxane by a
      mechanism that does not depend on an active cell-mediated process. In this
      report, we further investigate the ability of the host-[2]rotaxane to deliver
      peptides possessing a wide range of polarities (negatively charged, positively
      charged, polar, and apolar side chains) into live cells. Only in the presence of
      the host-[2]rotaxane were the Fl-peptides taken up by COS 7 and ES2 cells. Flow
      cytometry experiments demonstrated that the level of delivery is largely
      temperature and adenosine 5'-triphosphate (ATP) independent, and the membranes
      remain intact. Although the level of transport does depend upon the nature of the
      side chains, it does not correlate with calculated LogD values, indicating that
      an additional interaction with the host-[2]rotaxane is modifying the permeability
      properties of the peptide. The amount of Fl-peptides transported from an aqueous
      phase into a chloroform phase in the presence of the host-[2]rotaxane correlates
      with the intensity of cellular fluorescence. Extraction and U-tube studies show
      that the Fl-peptide can be released from its complex with the host-[2]rotaxane
      into an aqueous phase, and the host-[2]rotaxane can transport a greater than a
      stoichiometric amount of an Fl-peptide through a CHCl3 layer. These studies
      demonstrate the utility of the host-[2]rotaxane in delivering peptides of all
      polarities across a cell membrane.

PMID- 17516643
TI  - Cyclotetraphosphinophosphonium ions: synthesis, structures, and pseudorotation.
AB  - The first derivatives of catenated cyclotetraphosphinophosphonium cations,
      [(PhP)4PPhMe]+ (8a), [(MeP)4PMe2]+ (8b), [(CyP)4PPh2]+ (8d), [(CyP)4PMe2]+ (8e),
      [(PhP)4PPh2]+ (8f), [(PhP)4PMe2]+ (8g), are synthesized as
      trifluoromethanesulfonate (triflate, OSO2CF3-) salts through the reaction of
      cyclopentaphosphines (PhP)5 (4a) or (MeP)5 (4b) with methyl triflate (MeOTf) or
      by a net phosphenium ion [PR2+, R = Ph, Me; from R2PCl and trimethylsilyltriflate
      (Me3SiOTf)] insertion into the P-P bond of either cyclotetraphosphine (CyP)4 (3c)
      or cyclopentaphosphines (PhP)5 (4a) or (MeP)5 (4b). Although more conveniently
      prepared from 4a, compound 8a[OTf] can also be formed from (PhP)4 (3a) and MeOTf,
      and derivatives 8f[OTf] and 8g[OTf] are also accessible through reactions of 3a
      and R2PCl/Me3SiOTf with R = Ph or Me, respectively. A tetrachlorogallate salt of
      [(PhP)4PPhtBu]+ (8c) has been synthesized by alkylation of 4a with tBuCl/GaCl3.
      31P[1H] NMR parameters for all derivatives of 8 have been determined by iterative
      simulation of experimental data. Derivatives 8a[OTf], 8b[OTf], 8c[GaCl4],
      8e[OTf], 8f[OTf], and 8g[OTf] and have been characterized by X-ray
      crystallography, showing the most favorable all-trans configuration of
      substituents for the phosphine centers, thus minimizing steric interactions. Each
      derivative adopts a unique envelope or twist conformation of C1 symmetry. The
      effective C2 symmetry observed for 8b, d, e, f, and g in solution, signified by
      their 31P[1H] NMR AA'BB'X spin systems, implies a rapid conformational exchange
      for derivatives of 8. The core frameworks of the cations in the solid state are
      viewed as snapshots of different conformational isomers within the solution-phase
      pseudorotation process.

PMID- 17516645
TI  - Electron localization in the ground state of the ruthenium blue dimer.

PMID- 17516646
TI  - Nanocrystalline TiO2-catalyzed solid-state polymerization of diacetylene in the
      visible region.

PMID- 17516647
TI  - Interfacing silicon nanowires with mammalian cells.

PMID- 17516649
TI  - Determination of single molecule conductances of alkanedithiols by conducting
      atomic force microscopy with large gold nanoparticles.

PMID- 17516648
TI  - syn-1,2-Amino alcohols via diastereoselective allylic C-H amination.

PMID- 17516650
TI  - Superconductivity in an inorganic electride 12CaO x 7Al2O3:e-.

PMID- 17516651
TI  - Hexafunctionalized borromeates using olefin cross metathesis.
AB  - Employing well-established template-directed protocols, which depend upon dynamic
      covalent, coordinative, and noncovalent chemistry for their efficient outputs, we
      have synthesized, in a convergent manner, Borromeates composed of three identical
      macrocycles which present, diagonally in pairs, six exo-bidentate bipyridyl
      ligands and six endo-diiminopyridyl ligands, each carrying either pentenyloxy or
      p-tolylpentenyloxy substituents on their 4-positions, to six zinc(II) ions.

PMID- 17516652
TI  - Revisiting the stability of hexacenes.
AB  - The Strating-Zwanenberg photodecarbonylation was used to prepare hexacene (1).
      Compound 1 was found to be extremely unstable in solution, undergoing
      dimerization and oxidation. However, when generated in a polymer matrix, 1
      survived for more than 12 h under ambient conditions. Hexacenes substituted at
      the 6 and 15 positions with the phenyl, p-tert-butylphenyl, and mesityl groups
      were synthesized using the quinone reduction method, but these compounds were
      also shown to be unstable in solution.

PMID- 17516653
TI  - In vitro potential antioxidant activity of (1-->3),(1-->6)-beta-D-glucan and
      protein fractions from Saccharomyces cerevisiae cell walls.
AB  - (1-->3),(1-->6)-Beta-D-Glucan, a cell wall polysaccharide in many microorganisms,
      fungi and algae, is a well-known biological response modifier. Recently, it was
      found that (1-->3)-beta-D-glucan from Saccharomyces cerevisiae also exhibits
      antioxidative capabilities. In this study the antioxidative activity of the cell
      wall fractions of brewer's yeast was investigated. Particular emphasis was put on
      the question to which extent glucan is responsible for the antioxidative activity
      of the cell walls and how the other cell wall components might contribute. For
      the experiments yeast cell walls from brewery fermentations were used. Glucan was
      isolated by a three-step extraction procedure including a combination of hot
      water and enzymatic treatment. The level of (1-->3),(1-->6)-beta-D-glucan in the
      cell walls was analyzed enzymatically. The antioxidant activity was determined by
      electron paramagnetic resonance spectrometry and Trolox equivalent antioxidant
      capacity assay. The results show that the antioxidative activity of yeast cell
      wall proteins exceeds that of beta-glucan greatly. Especially aromatic side
      chains and free thiols from denatured proteins seem to work as antioxidants.

PMID- 17516654
TI  - Synthesis and resistance to in vitro proteolysis of transglutaminase cross-linked
      phaseolin, the major storage protein from Phaseolus vulgaris.
AB  - The ability of phaseolin to act as an acyl donor and acceptor substrate of
      transglutaminase was studied by using an enzyme isolated from Streptoverticillium
      mobarense. Phaseolin, a trimeric storage protein from Phaseolus vulgaris L., was
      shown to possess both glutamine and lysine residues reactive for the enzyme. The
      extent of transglutaminase-catalyzed cross-linking has been studied in function
      of both incubation time and enzyme concentration. Native- and SDS-PAGE
      demonstrated that phaseolin is intra- and intermolecularly cross-linked by
      transglutaminase and gives rise to different polymers as well as to modified
      forms of the protein having a similar molecular weight but lower Stokes radius if
      compared to unmodified phaseolin. Cross-linked phaseolin was found to be more
      resistant to proteolytic cleavage than the unmodified counterpart, as
      demonstrated by in vitro trypsin and pepsin digestion experiments. This behavior
      could suggest novel possible uses of the transglutaminase-modified phaseolin.

PMID- 17516655
TI  - Isolation and characterization of a low molecular weight peptide contained in
      sourdough.
AB  - To investigate a sourdough-specific peptide, low molecular weight peptides were
      extracted from sourdough. The peptide fraction was subjected to two kinds of
      chromatography to separate the peptides. Reverse-phase chromatography of the
      peptide fraction in the sourdough showed certain specific peptides. The specific
      peptide fraction was further separated by gel filtration chromatography. Liquid
      chromatography tandem mass spectrometry analysis identified one of the peptides
      as VPFGVG (six-mer). This sequence was estimated to occur at the 287-292 position
      of a low molecular weight glutenin subunit. The peptide (designed as SDP1) was
      produced by proteases derived from wheat flour. SDP1 showed angiotensin
      converting enzyme (ACE) inhibitory activity, and the 50% inhibitory peptide
      concentration (IC50) was 336 microM. It is possible that the SDP1 peptide
      partially confers ACE inhibitory activity in sourdough.

PMID- 17516656
TI  - Relationship between phenolic compounds, anthocyanins content and antioxidant
      activity in colored barley germplasm.
AB  - Barley and its products are good sources of antioxidants. This experiment was
      conducted to examine the classification and concentration of phenolic compounds,
      proanthocyanidins, and anthocyanins in 127 lines of colored barley. Their
      relationship with 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging
      activity was also examined. Barley was placed into seven groups using the
      colorimeter: hulled (black 1, black 2, black 3, and purple) and unhulled (black,
      blue, and purple). The contents of phenolic compounds and anthocyanins were
      analyzed by using HPLC. The average content of phenolic compounds in unhulled
      barley groups (268.6 microg/g) was higher than that in hulled (207.0 microg/g) (P
      > 0.05). The proanthocyanidins content was determined by modified vanillin assay.
      The average content of proanthocyanidins was significantly higher in purple and
      blue barley groups compared with black (P < 0.05). The content of anthocyanins
      varied from 13.0 to 1037.8 microg/g. Purple and blue barley groups contained
      higher average contents of anthocyanins than black (P < 0.05). The most common
      anthocyanin in the purple barley groups was cyanidin 3-glucoside, whereas
      delphinidin 3-glucoside was the most abundant anthocyanin in the blue and black
      groups. In colored barley, DPPH radical scavenging activity had high positive
      correlation to the content of phenolic compounds and proanthocyanidins.

PMID- 17516657
TI  - Anti-oxidant constituents of the roots and stolons of licorice (Glycyrrhiza
      glabra).
AB  - As part of a search for new cancer chemopreventive agents, a new chalcone
      derivative (1), a novel group of neolignan lipid esters (2), and seven known
      phenolic compounds (formononetin, glabridin, hemileiocarpin, hispaglabridin B,
      isoliquiritigenin, 4'-O-methylglabridin, and paratocarpin B) (3-9) were isolated
      from the roots and stolons of licorice (Glycyrrhiza glabra). The structures of
      compound 1 and the individual components of isolate 2 were elucidated using
      various spectroscopic and chemical methods. All isolates were tested in an
      authentic peroxynitrite anti-oxidant assay. Of these compounds, hispaglabridin B
      (6), isoliquiritigenin (7), and paratocarpin B (9) were found to be the most
      potent anti-oxidant agents. Furthermore, isoliquiritigenin (7) was demonstrated
      to prevent the incidence of 1,2-dimethylhydrazine-induced colon and lung tumors
      in mice when administered at a dose of 300 mg/kg.

PMID- 17516658
TI  - Dynamics of tryptophan in the histidine-containing phosphocarrier protein of
      Streptomyces coelicolor: evidence of multistate equilibrium unfolding.
AB  - The nanosecond dynamics of the single tryptophan, Trp10, of HPr from Streptomyces
      coelicolor, HPrsc, has been monitored at different pHs. Time-resolved
      fluorescence methods and DOSY measurements have been used to map the compactness
      of the protein. At low pHs, where a molten globule-like species has been
      described, the correlation times from fluorescence showed an abrupt change as the
      pH was increased. When the protein was folded (above pH 4), two correlation times
      were observed, which remained practically constant up to pH 9.5. The long
      correlation time, around 7.5 ns, corresponds to the global rotational motion of
      the protein, since this value is in agreement with that determined theoretically
      from hydrodynamic measurements. The short correlation time, around 1.4 ns, must
      report on fast movements of the protein segment containing the tryptophan
      residue. On the other hand, fluorescence lifetimes showed the same abrupt change
      as the correlation times at low pH, but, in addition, a sigmoidal change with a
      pKa approximately 4.3 was also observed. On the basis of the modeled structure of
      HPrsc, this last transition could be due to the proximity of Glu12 to Trp10. The
      changes monitored by the fluorescence lifetimes agree with those observed
      previously by steady-state fluorescence, CD, and ANS binding experiments. Taken
      together, these data suggest a multistate equilibrium during folding of HPrsc
      starting from low pHs.

PMID- 17516659
TI  - The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor
      antibiotic biosynthetic pathway.
AB  - The SgcC4 l-tyrosine 2,3-aminomutase (SgTAM) catalyzes the formation of (S)-beta
      tyrosine in the biosynthetic pathway of the enediyne antitumor antibiotic C-1027.
      SgTAM is homologous to the histidine ammonia lyase family of enzymes whose
      activity is dependent on the methylideneimidazole-5-one (MIO) cofactor. Unlike
      the lyase enzymes, SgTAM catalyzes additional chemical transformations resulting
      in an overall stereospecific 1,2-amino shift in the substrate l-tyrosine to
      generate (S)-beta-tyrosine. Previously, we provided kinetic, spectroscopic, and
      mutagenesis data supporting the presence of MIO in the active site of SgTAM
      [Christenson, S. D.; Wu, W.; Spies, A.; Shen, B.; and Toney, M. D. (2003)
      Biochemistry 42, 12708-12718]. Here we report the first X-ray crystal structure
      of an MIO-containing aminomutase, SgTAM, and confirm the structural homology of
      SgTAM to ammonia lyases. Comparison of the structure of SgTAM to the l-tyrosine
      ammonia lyase from Rhodobacter sphaeroides provides insight into the structural
      basis for aminomutase activity. The results show that SgTAM has a closed active
      site well suited to retain ammonia and minimize the formation of lyase
      elimination products. The amino acid determinants for substrate recognition and
      catalysis can be predicted from the structure, setting the framework for detailed
      mechanistic investigations.

PMID- 17516660
TI  - Mutability of an HNH nuclease imidazole general base and exchange of a
      deprotonation mechanism.
AB  - Several unique protein folds that catalyze the hydrolysis of phosphodiester bonds
      have arisen independently in nature, including the PD(D/E)XK superfamily
      (typified by type II restriction endonucleases and many recombination and repair
      enzymes) and the HNH superfamily (found in an equally wide array of enzymes,
      including bacterial colicins and homing endonucleases). Whereas the identity and
      position of catalytic residues within the PD(D/E)XK superfamily are highly
      variable, the active sites of HNH nucleases are much more strongly conserved. In
      this study, the ability of an HNH nuclease to tolerate a mutation of its most
      conserved catalytic residue (its histidine general base), and the mechanism of
      the most active enzyme variant, were characterized. Conversion of this residue
      into several altered chemistries, glutamine, lysine, or glutamate, resulted in
      measurable activity. The histidine to glutamine mutant displays the highest
      residual activity and a pH profile similar to that of the wild-type enzyme. This
      activity is dependent on the presence of a neighboring imidazole ring, which has
      taken over as a less efficient general base for the reaction. This result implies
      that mutational pathways to alternative HNH-derived catalytic sites do exist but
      are not as extensively or successfully diverged or reoptimized in nature as
      variants of the PD(D/E)XK nuclease superfamily. This is possibly due to multiple
      steric constraints placed on the compact HNH motif, which is simultaneously
      involved in protein folding, DNA binding, and catalysis, as well as the use of a
      planar, aromatic imidazole group as a general base.

PMID- 17516661
TI  - The N-terminal A domain of Staphylococcus aureus fibronectin-binding protein A
      binds to tropoelastin.
AB  - Staphylococcus aureus is an important human pathogen. Its virulence factors
      include a variety of MSCRAMMs (microbial surface component recognizing adhesive
      matrix molecules), each capable of binding specifically to the host extracellular
      matrix. The fibronectin-binding protein, FnBPA, has been shown previously to bind
      immobilized fibronectin, fibrinogen, and alpha-elastin peptides. Here we show
      that region A of FnBPA (rAFnBPA) binds to recombinant human tropoelastin. Binding
      occurs to three separate truncates of tropoelastin, encompassing domains 2-18, 17
      27, and 27-36, signifying that the interaction occurs at multiple sites. The
      greatest affinity was for the N-terminal truncate. We observed a pH dependency
      for the rAFnBPA-tropoelastin interaction with strong, nonsaturable binding at low
      pH. The interaction ceased at higher pH. These data support a model of surface
      surface interactions between the negative charges present on rAFnBPA and the
      positive lysines of tropoelastin. A protein lacking the negatively charged C
      terminal fibronectin-binding motif of the A domain of FnBPA and another construct
      lacking subdomain N1 were both capable of binding immobilized tropoelastin with a
      lower affinity. The binding properties of five site-directed mutants of rAFnBPA
      were compared with wild-type rAFnBPA. There was no decreased affinity for
      immobilized tropoelastin, in contrast to the defective binding of these mutants
      to alpha-elastin and fibrinogen. The data indicate novel interactions between
      tropoelastin and FnBPA that include the use of surface charges. These results
      demonstrate that FnBPA is capable of directly binding tropoelastin prior to its
      incorporation into elastin.

PMID- 17516662
TI  - Wear particles generated from studded tires and pavement induces inflammatory
      reactions in mouse macrophage cells.
AB  - Health risks associated with exposure to airborne particulate matter (PM) have
      been shown epidemiologically as well as experimentally, pointing to both
      respiratory and cardiovascular effects. These health risks are of increasing
      concern in society, and to protect public health, a clarification of the toxic
      properties of particles from different sources is of importance. Lately, wear
      particles generated from traffic have been recognized as a major contributing
      source to the overall particle load, especially in the Nordic countries where
      studded tires are used. The aim of this study was to further investigate and
      compare the ability to induce inflammatory mediators of different traffic-related
      wear particles collected from an urban street, a subway station, and studded tire
      pavement wear. Inflammatory effects were measured as induction of nitric oxide
      (NO), IL-6, TNF-alpha, arachidonic acid (AA), and lipid peroxidation after
      exposure of the murine macrophage like cell line RAW 264.7. In addition, the
      redox potential of the particles was measured in a cell-free system. The results
      show that all particles tested induce IL-6, TNF-alpha, and NO, and those from the
      urban street were the most potent ones. In contrast, particles collected from a
      subway station were most potent to induce lipid peroxidation, AA release, and
      formation of ROS. Particles from studded tire-pavement wear, generated using a
      road simulator, were able to induce inflammatory cytokines, NO, lipid
      peroxidation, and ROS formation. Interestingly, particles generated from pavement
      containing granite as the main stone material were more potent than those
      generated from pavement containing quartzite as the main stone material.

PMID- 17516664
TI  - How does the nature of the steric stabilizer affect the pickering emulsifier
      performance of lightly cross-linked, acid-swellable poly(2-vinylpyridine)
      latexes?
AB  - A near-monodisperse styrene-functionalized poly[2-(dimethylamino)ethyl
      methacrylate] (PDMA) macromonomer was evaluated as a reactive steric stabilizer
      for the preparation of poly(2-vinylpyridine (P2VP) latexes via emulsion
      polymerization. The solution pH was shown to be a critical parameter for
      successful syntheses: stable latexes with minimal coagulum were only obtained at
      (or above) neutral pH. The presence of the grafted PDMA stabilizer in a near
      monodisperse P2VP latex of 280 nm diameter was indicated by FT-IR spectroscopy
      and quantified at 6.0 wt % using 1H NMR spectroscopy. XPS studies confirmed that
      this stabilizer was located at the latex surface, as expected. Combined DLS and
      electrophoretic data indicated that these PDMA-P2VP particles exist in three
      states depending on the solution pH: swollen cationic microgels were obtained
      below pH 4.1, nonsolvated latex particles with a cationic stabilizer layer were
      obtained at intermediate pH, and flocculated latex particles with neutral PDMA
      stabilizer chains were obtained at around pH 8.5. Finally, this PDMA-P2VP latex
      was shown to be a superior Pickering emulsifier for stabilizing water-in-1
      undecanol emulsions than either a poly(ethylene glycol)-stabilized P2VP latex or
      a charge-stabilized P2VP latex. This serves to illustrate the important role
      played by the steric stabilizer in determining particle wettability.

PMID- 17516663
TI  - Mutation of cysteine residue 455 to alanine in human topoisomerase IIalpha
      confers hypersensitivity to quinones: enhancing DNA scission by closing the N
      terminal protein gate.
AB  - Several quinone-based metabolites of industrial and environmental toxins are
      potent topoisomerase II poisons. These compounds act by adducting the protein,
      and previous studies suggest that they increase levels of enzyme-associated DNA
      strand breaks by at least two potential mechanisms. Quinones act directly on the
      DNA cleavage-ligation equilibrium of topoisomerase II by inhibiting the rate of
      ligation. They also block the N-terminal gate of the protein, thereby stabilizing
      topoisomerase II in its "closed clamp" form and trapping DNA in the central
      annulus of the enzyme. It has been proposed that this latter activity enhances
      DNA cleavage by increasing the population of enzyme molecules with DNA in their
      active sites, but a causal relationship has not been established. In order to
      more fully characterize the mechanistic basis for quinone action against
      topoisomerase II, the present study characterized the sensitivity of human
      topoisomerase IIalpha carrying a Cys455-->Ala mutation (top2alphaC455A) toward
      quinones. Cys455 was identified as a site of quinone adduction by mass
      spectrometry. The mutant enzyme was approximately 1.5-2-fold hypersensitive to
      1,4-benzoquinone and the polychlorinated biphenyl quinone 4'Cl-2,5pQ, but it
      displayed wild-type sensitivity to traditional topoisomerase II poisons. The
      ability of 1,4-benzoquinone to inhibit DNA ligation mediated by top2alphaC455A
      was similar to that of wild-type topoisomerase IIalpha. However, the quinone
      induced approximately 3 times the level of clamp closure with the mutant enzyme.
      These findings strongly support the hypothesis that the ability of quinones to
      block the N-terminal gate of the type II enzyme contributes to their actions as
      topoisomerase II poisons.

PMID- 17516665
TI  - Electrochemistry of non-redox-active poly(propylenimine) and poly(amidoamine)
      dendrimers at liquid-liquid interfaces.
AB  - The electrochemistry of a series of dendrimers was examined at the interface
      between two immiscible electrolyte solutions (ITIES), enabling study of non-redox
      active dendrimers. Different generations of poly(propylenimine) (DAB-AM-n) and
      poly(amidoamine) (PAMAM) dendrimers were studied. In their protonated states, the
      dendrimers were transferred across the ITIES, with the electrochemical behavior
      observed depending on the dendrimer family, the generation number, and the
      experimental pH. The electrochemistry of the lower generations studied was
      characterized by well-defined peaks for both dendrimer families and with small
      peak-peak separations in the case of the PAMAM family. The voltammetry of the
      higher generations was more complex, showing distorted voltammograms and
      instability of the interface. The charges of the transferring dendrimers were
      calculated by convolution of the voltammetric data and were similar to the
      theoretical charges for DAB-AM-n. For PAMAM, only the lowest generation exhibited
      reversible behavior, with higher generations having irreversible behavior. Using
      cyclic voltammetry, low micromolar concentrations of the dendrimers were
      detected. The results show that electrochemistry at the ITIES can be a useful
      method for characterization of ionizable dendrimers and that voltammetry can be a
      simple method for detection of low concentrations of these multicharged species.

PMID- 17516666
TI  - Polymer encapsulation within giant lipid vesicles.
AB  - We report encapsulation of polymers and small molecules within individual giant
      lipid vesicles (GVs; 3-80 microm), as determined by confocal fluorescence
      microscopy. Polymer-bound or free dyes were encapsulated within GVs by including
      these molecules in the aqueous solution during vesicle formation via gentle
      hydration. Encapsulation efficiencies of individual GVs (EE(ind)) were determined
      from the fluorescence intensity ratio inside vs outside the vesicle. EE(ind)
      varied considerably from vesicle to vesicle, with interior solute concentrations
      for GVs within the same batch ranging from much less than to slightly more than
      the initial concentration. The majority of GVs had high internal concentrations
      of polymer or small-molecule encapsulants equal to or slightly greater than the
      external concentration. EE(ind) decreased for high molecular weight polymers
      (e.g., dextran 500 000), but was relatively insensitive to the GV diameter,
      membrane composition, or incubation temperature in our experiments. Knowledge of
      EE(ind) is important for quantitative evaluation of reactions occurring within
      GVs (e.g., enzymatic processes) and for optimizing encapsulation conditions.

PMID- 17516667
TI  - Direct measurement of critical nucleus size in confined volumes.
AB  - In crystallization, the critical nucleus size is of pivotal importance. Above
      this size, it is favorable for the new crystalline phase to form; below this
      size, the clusters will tend to dissolve rather than grow. To date, there has
      been no direct method for measuring the critical nucleus size. Instead, the size
      is typically calculated from the variation of crystallization rates with
      temperature. This involves using bulk values of the interfacial tension and
      enthalpy of fusion, which are inappropriate for small critical nucleus sizes.
      Here, we present a direct method for measuring the size of the critical nucleus,
      based on observing crystallization temperatures of materials within
      microemulsions. Using this approach, the number of molecules in the critical
      nucleus can be found simply by measuring the droplet size. Data on the freezing
      of water in water-in-oil microemulsions with and without the nucleating agent,
      heptacosanol, are presented to support our hypothesis. The results show that the
      critical nucleus contains 90-350 ice molecules for water pool radii of
      approximately 1.2-1.8 nm for the heptacosanol-doped microemulsions in which
      heterogeneous nucleation is initiated at the droplet interface. For the
      microemulsions without heptacosanol, the critical nucleus contains 70-210 ice
      molecules for water pool radii of approximately 1.2-1.8 nm. The smaller values
      arise because homogeneous nucleation occurs and therefore the crystallization
      temperatures are lower. We can also determine how bulk properties are perturbed
      at the nanoscale, and we find that the ratio of the ice-water interfacial tension
      to the enthalpy of fusion decreases significantly for water pool radii that are
      <2 nm.

PMID- 17516668
TI  - Interactions of novel, nonhemolytic surfactants with phospholipid vesicles.
AB  - PEG-12-acyloxystearates constitute a novel class of pharmaceutical solubilizers
      and are synthesized from polyethylene glycol and 12-hydroxystearic acid, which
      has been esterified with a second acyl chain. The hemolytic activity of these
      surfactants decreases drastically with increasing pendant acyloxy chain length,
      and surfactants with an acyloxy chain of 14 carbon atoms or more are essentially
      nonhemolytic. In this paper, the interactions of PEG-12-acyloxystearates (acyloxy
      chain lengths ranging from 8 to 16 carbon atoms) with phosphatidylcholine
      vesicles, used as a model system for erythrocyte membranes, were studied in
      search of an explanation for the large variations in hemolytic activity.
      Surfactant-induced alterations of membrane permeability were investigated by
      studying the leakage of vesicle-entrapped calcein. It was found that all of the
      surfactants within the series interact with the vesicle membranes and cause slow
      leakage at elevated surfactant concentrations, but with large variations in
      leakage kinetics. The initial leakage rate decreases rapidly with increasing
      pendant acyloxy chain length. After prolonged incubation, on the other hand, the
      leakage is not a simple function of acyloxy chain length. The effect of the
      surfactants on membrane integrity was also investigated by turbidity measurements
      and cryo-transmission electron microscopy. At a surfactant/lipid molar ratio of
      0.4, the vesicle membranes are saturated with surfactant. When the
      surfactant/lipid molar ratio is further increased, the vesicle membranes are
      progressively solubilized into mixed micelles. The rate of this process decreases
      strongly with increasing acyloxy chain length. When comparing the results of the
      different experiments, it can be concluded that there is no membrane
      permeabilization below saturation of the vesicle membranes. The large variations
      in the kinetics suggest that several steps are involved in the mechanism of
      leakage induced by PEG-12-acyloxystearates and that their relative rates vary
      with acyloxy chain length. The slow kinetics may in part be explained by the low
      critical micelle concentrations (CMCs) exhibited by the surfactants. The CMCs
      were found to be in the range of 0.003-0.025 microM.

PMID- 17516669
TI  - Vertical and directional insertion of helical peptide into lipid bilayer
      membrane.
AB  - A novel helical hexadecapeptide carrying a poly(ethylene glycol) (PEG) chain at
      the N terminal was synthesized. The N and C terminals of the compound are labeled
      with a fluorescein isothiocyanate (FITC) group and an N-ethylcarbazolyl group
      (ECz), respectively. An octapeptide carrying the same groups and a
      hexadecapeptide without a PEG chain were also synthesized and used as control. A
      mixture of the peptide and dimyristoylphosphatidylcholine was sonicated in a
      buffer to prepare the liposome. The orientation as well as direction of the
      helical segment in the lipid bilayer were analyzed by quenching experiments of
      the FITC and the ECz fluorescence. The results clearly indicated that the helical
      segment of the peptide penetrated into the lipid bilayer with vertical
      orientation in both the gel and liquid crystalline states of the lipid bilayer.
      Notably, the bulky N terminal was left behind in the outer aqueous phase of
      liposome, meaning that the C terminal of the peptide points to the inner aqueous
      phase of liposome. The insertion mode of the helical peptide into a bilayer
      membrane is therefore well-regulated in terms of the orientation and the
      directionality by designing the balance between the PEG chain and the helix
      length. The methodology presented here will initiate a way to construct
      artificial functional molecular systems that can induce vectorial transport
      phenomena as seen in biological systems.

PMID- 17516670
TI  - pH responsiveness of block copolymer vesicles with a polypeptide corona.
AB  - The aggregation behavior of polybutadiene165-block-poly(L-lysine)88 in saline
      solution was studied by combined static and dynamic light scattering analyses.
      Vesicles were observed if the polypeptide segment was in a 100% coil conformation
      (pH 7.0) or in an 80% alpha-helical conformation (pH 10.3). At the higher pH,
      aggregates were smaller in size (hydrodynamic radius: 364 nm --> 215 nm) and
      chains were more densely packed at the core-corona interface (interchain
      distance: 3.2 nm --> 2.4 nm). Changes in size and structure could be explained in
      basic terms of colloid stabilization without considering a secondary structure
      effect.

PMID- 17516671
TI  - Small angle neutron scattering investigations (SANS) of polyelectrolyte
      multilayer capsules templated on human red blood cells.
AB  - Polyelectrolyte capsules were fabricated by layer-by-layer deposition of
      poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) on
      glutardialdehyde fixed human erythrocytes and subsequent core dissolution using
      NaOCl as an oxidizing agent. SANS together with confocal laser scanning
      microscopy (CLSM) were applied to study capsule topology and interior as well as
      the layer thickness as a function of the deposition protocol, layer number, ionic
      concentration, and temperature treatment. The capsules contained various amounts
      of trapped polyelectrolyte. Retention depended on the order of polyelectrolyte
      deposition and layer number, which influenced layer permeability. The capsule
      wall thickness was found to be much smaller (3-4.5 nm in total) than what was
      known for polyelectrolyte multilayer walls, where every single layer contributes
      about 1.8 nm to the total thickness. NaCl (0.1 mM) caused a layer thickness
      decrease by 16%. Annealing at 70 degrees C induced capsule shrinking together
      with an increase of the wall thickness by 85% and wall density by 12%.

PMID- 17516672
TI  - Characterization of the high-pressure structures and phase transformations in
      SnO2. A density functional theory study.
AB  - Theoretical investigations concerning the high-pressure polymorphs, the equations
      of state, and the phase transitions of SnO2 have been performed using density
      functional theory at the B3LYP level. Total energy calculations and geometry
      optimizations have been carried out for all phases involved, and the following
      sequence of structural transitions from the rutile-type (P42/mnm) driven by
      pressure has been obtained (the transition pressure is in parentheses): --> CaCl2
      type, Pnnm (12 GPa) --> alpha-PbO2-type, Pbcn (17 GPa) --> pyrite-type, Pa (17
      GPa) --> ZrO2-type orthorhombic phase I, Pbca (18 GPa) --> fluorite-type, Fmm (24
      GPa) --> cotunnite-type orthorhombic phase II, Pnam (33 GPa). The highest bulk
      modulus values, calculated by fitting pressure-volume data to the second-order
      Birch-Murnaghan equation of state, correspond to the cubic pyrite and the
      fluorite-type phases with values of 293 and 322 GPa, respectively.

PMID- 17516674
TI  - Excess thermodynamics of mixtures involving xenon and light linear alkanes by
      computer simulation.
AB  - Excess molar enthalpies and excess molar volumes as a function of composition for
      liquid mixtures of xenon + ethane (at 161.40 K), xenon + propane (at 161.40 K)
      and xenon + n-butane (at 182.34 K) have been obtained by Monte Carlo computer
      simulations and compared with available experimental data. Simulation conditions
      were chosen to closely match those of the corresponding experimental results. The
      TraPPE-UA force field was selected among other force fields to model all the
      alkanes studied, whereas the one-center Lennard-Jones potential from Bohn et al.
      was used for xenon. The calculated H(m)(E) and V(m)(E) for all systems are
      negative, increasing in magnitude as the alkane chain length increases. The
      results for these systems were compared with experimental data and with other
      theoretical calculations using the SAFT approach. An excellent agreement between
      simulation and experimental results was found for xenon + ethane system, whereas
      for the remaining two systems, some deviations that become progressively more
      significant as the alkane chain length increases were observed.

PMID- 17516675
TI  - Enhanced efficiency of direct-space structure solution from powder X-ray
      diffraction data in the case of conformationally flexible molecules.
AB  - A strategy is reported for assessing the feasibility of molecular conformations
      within direct-space structure-solution calculations of organic molecular crystal
      structures from powder X-ray diffraction data, focusing in particular on the
      genetic algorithm technique for structure solution in which fitness is defined as
      a function of the whole-profile figure-of-merit Rwp. The strategy employs a
      readily computed distance-based function to assess the feasibility of the
      molecular conformation in each trial structure generated in the genetic algorithm
      calculation, and structures considered to have low-feasibility conformations are
      penalized within the evolutionary process. The strategy is shown to lead to
      significant improvements in the success rate of structure-solution calculations
      in the case of flexible molecules with a significant number of conformational
      degrees of freedom.

PMID- 17516673
TI  - Use of 13Calpha chemical shifts in protein structure determination.
AB  - A physics-based method aimed at determining protein structures by using NOE
      derived distances together with observed and computed 13C chemical shifts is
      proposed. The approach makes use of 13Calpha chemical shifts, computed at the
      density functional level of theory, to obtain torsional constraints for all
      backbone and side-chain torsional angles without making a priori use of the
      occupancy of any region of the Ramachandran map by the amino acid residues. The
      torsional constraints are not fixed but are changed dynamically in each step of
      the procedure, following an iterative self-consistent approach intended to
      identify a set of conformations for which the computed 13Calpha chemical shifts
      match the experimental ones. A test is carried out on a 76-amino acid, all-alpha
      helical protein; namely, the Bacillus subtilis acyl carrier protein. It is shown
      that, starting from randomly generated conformations, the final protein models
      are more accurate than an existing NMR-derived structure model of this protein,
      in terms of both the agreement between predicted and observed 13Calpha chemical
      shifts and some stereochemical quality indicators, and of similar accuracy as one
      of the protein models solved at a high level of resolution. The results provide
      evidence that this methodology can be used not only for structure determination
      but also for additional protein structure refinement of NMR-derived models
      deposited in the Protein Data Bank.

PMID- 17516676
TI  - Micro-DSC and rheological studies of interactions between methylcellulose and
      surfactants.
AB  - The effects of a cationic surfactant, cetyltrimethylammonium bromide (CTAB), on
      the gelation of methylcellulose (MC) in aqueous solutions have been investigated
      by micro differential scanning calorimetry (micro DSC) and rheology.
      Methylcellulose had a weight average molecular weight of 310,000 and a degree of
      substitution of 1.8. The concentration of MC was kept at 0.5 wt % (0.016 mM) and
      1 wt % (0.032 mM), and the concentration of CTAB in the MC solutions was varied
      from 0 to 0.6 wt % (16.5 mM). Upon heating, a single endothermic peak, which is
      due to the hydrophobic association and gelation of MC, shifts to lower
      temperatures with increasing CTAB for CTAB < or = CMC (0.93 mM or 0.034 wt %),
      and then it shifts to higher temperatures lineally with CTAB for CTAB > CMC. At
      the same time, the endothermic enthalpy decreases with increasing CTAB
      concentration. Even though CTAB shows a significant "salt-in" effect on the
      gelation of MC, it does not affect the pattern of the sol-gel transition as well
      as the gel strength of MC. At the highest concentration of CTAB, 0.60 wt %, MC is
      still able to form a gel. At a given ratio of CTAB/MC, the effect of CTAB on MC
      becomes stronger when the MC concentration is lower. The results for the MC-CTAB
      system are compared with an ionic surfactant, SDS and the significant differences
      in affecting the gelation of MC between two surfactants are recognized.

PMID- 17516677
TI  - Selective interactions of a few acridinium derivatives with single strand DNA:
      study of photophysical and DNA binding interactions.
AB  - Novel acridinium derivatives 1-3, wherein steric factors have been varied
      systematically through substitution at the ninth position of the acridinium ring,
      were synthesized and their interactions with single strand and double strand DNA
      have been investigated through photophysical, biophysical, and microscopic
      techniques. The acridinium derivative 1 exhibited quantitative fluorescence
      yields (phi f approximately =1) and high lifetime of 35 ns, while significantly
      lower fluorescence yields of 0.11 and 0.02 and lifetimes of 3.5 and 1.2 ns were
      observed for 2 and 3, respectively. The derivatives 1 and 2 having 2-methylphenyl
      and 2,4-dimethylphenyl substituents at the ninth position of the acridinium ring
      showed selective interactions with single strand DNA (ssDNA) with association
      constants of KssDNA = 6.3-6.6 x 10(4) M(-1), while negligible interactions were
      observed with double strand DNA (dsDNA). In contrast, the derivative 3 with 2,6
      dimethylphenyl substitution showed negligible interactions with both ssDNA and
      dsDNA. Studies with a series of 19-mer oligonucleotides indicate that these
      derivatives exhibit significant selectivity for the sequences rich in guanosine
      (ca. 3-fold) as compared to the cytosine-rich sequences. These derivatives with
      high water solubility and the ability to distinguish between ssDNA and dsDNA
      through changes in fluorescence emission can be used as fluorescent probes for
      understanding the role of ssDNA in various biological processes and to study
      various DNA-ligand interactions.

PMID- 17516678
TI  - Determination of the absolute configuration of a chiral oxadiazol-3-one calcium
      channel blocker, resolved using chiral chromatography, via concerted density
      functional theory calculations of its vibrational circular dichroism, electronic
      circular dichroism, and optical rotation.
AB  - The chiral oxadiazol-3-one 2 has recently been shown to exhibit myocardial
      calcium entry channel blocking activity, substantially higher than that of
      diltiazem. To determine the enantioselectivity of this activity, the enantiomers
      of 2 have been resolved using chiral chromatography. The absolute configuration
      (AC) of 2 has been determined by comparison of density functional theory (DFT)
      calculations of its vibrational circular dichroism (VCD) spectrum, electronic
      circular dichroism (ECD) spectrum, and optical rotation (OR) to experimental VCD,
      ECD, and OR data. All three chiroptical properties yield identical ACs; the AC of
      2 is unambiguously determined to be S(+)/R(-).

PMID- 17516679
TI  - Dependence of N-nitrosodimethylamine photodecomposition on the irradiation
      wavelength: excitation to the s(2) state as a doorway to the dimethylamine
      radical ground-state chemistry.
AB  - The photochemistry of N-nitrosodimethylamine after excitation to the S(1) and
      S(2) states has been studied with the complete active space self-consistent field
      method (CASSCF) and the second-order multiconfigurational perturbation theory
      (CASPT2). The calculated vertical transitions agree with the experiment: the S(0)
      --> S(1) transition occurs at 3.29 eV (f = 0.003 au), the S(0) --> S(2)
      transition at 5.30 eV (f = 0.17 au) and the first excited triplet state is
      computed at 2.48 eV. Solvent effects have been reproduced by means of PCM
      calculations. It is shown that excitation to S(1) and S(2) yields the same
      photoproducts: (CH(3))(2)N (1(2)B(1)) and NO (X(2)Pi). However, while on S1 the
      process is adiabatic, the process on S(2) implies an ultrafast decay through a
      planar S(2)/S(1) conical intersection. Our calculations are consistent with the
      reversibility of the N-N dissociation after irradiation at 363.5 nm and the
      observed dimethylamine radical reactions when irradiated at 248 nm, namely, H
      extrusion, a one-step process (41.3 kcal/mol), and methyl radical extrusion, a
      two-step process (44.0 kcal/mol and 31.5 kcal/mol). Finally, two more aspects are
      considered: (i) the topology of the T(1) surface where two minima have been found
      to correlate with the phosphorescence emission band and (ii) the influence of
      tautomerizations which is shown to be neglectable.

PMID- 17516680
TI  - p-n Semiconductor membrane for electrically tunable ion current rectification and
      filtering.
AB  - We show that a semiconductor membrane made of two thin layers of opposite (n- and
      p-) doping can perform electrically tunable ion current rectification and
      filtering in a nanopore. Our model is based on the solution of the 3D Poisson
      equation for the electrostatic potential in a double-cone nanopore combined with
      a transport model. It predicts that, for appropriate biasing of the membrane
      electrolyte system, transitions from ohmic behavior to sharp rectification with
      vanishing leakage current are achievable. Furthermore, ion current rectifying and
      filtering regimes of the nanopore correspond to different charge states in the p
      n membrane, which can be tuned with appropriate biasing of the n- and p- layers.

PMID- 17516681
TI  - Lateral self-aligned p-type In2O3 nanowire arrays epitaxially grown on Si
      substrates.
AB  - Lateral orientated growth of In2O3 nanowire (NW) and nanorod (NR) arrays has been
      achieved by a vapor transport and condensation method on (001) and (111) surfaces
      of Si substrates. The single crystalline In2O3 NWs and NRs were grown along [211]
      in parallel to the Si +/-[110] and lying in the substrate plane. The electrical
      measurements show that the In2O3 NWs are p-type semiconductor. By N+ doping, the
      resistivity of the In2O3 NWs has been tuned. The lateral self-aligned In2O3 NW
      and NR arrays on Si can offer some unique advantages for fabricating parallel
      nanodevices that can be integrated directly with silicon technology.

PMID- 17516682
TI  - Soft lithographic fabrication of high Q polymer microcavity arrays.
AB  - As new synthetic, low-loss polymers are developed, polymer optical cavities are
      experiencing a revolution, in both fabrication design and functionality.
      Recently, a fabrication technique was developed that enabled planar arrays of
      polymeric resonators to achieve cavity Q factors greater than 1 million. In the
      present letter, this molding technique is expanded to fabricate resonators from
      polymers that have either thermal or UV curing mechanisms. The quality factors
      and broad band spectrum of these devices are determined at 680, 1300, and 1550
      nm. These resonant cavities demonstrate quality factors which are competitive
      with photonic crystals and microdisk resonators.

PMID- 17516684
TI  - Electron turbulence at nanoscale junctions.
AB  - Electron transport through a nanostructure can be characterized in part using
      concepts from classical fluid dynamics. It is thus natural to ask how far the
      analogy can be taken and whether the electron liquid can exhibit nonlinear
      dynamical effects such as turbulence. Here we present an ab initio study of the
      electron dynamics in nanojunctions which reveals that the latter indeed exhibits
      behavior quite similar to that of a classical fluid. In particular, we find that
      a transition from laminar to turbulent flow occurs with increasing current,
      corresponding to increasing Reynolds numbers. These results reveal unexpected
      features of electron dynamics and shed new light on our understanding of
      transport properties of nanoscale systems.

PMID- 17516683
TI  - Wetting driven self-assembly as a new approach to template-guided fabrication of
      metal nanopatterns.
AB  - Wetting driven self-assembly (WDSA) of appropriate materials in their liquid
      state on organic monolayer nanopatterns consisting of wettable (lyophilic)
      surface features surrounded by a nonwettable (lyophobic) monolayer background is
      shown to provide the basis of a versatile new approach to template-guided
      fabrication of metal nanopatterns. Monolayer nanopatterns with planned
      distributions of lyophilic/lyophobic surface regions are conveniently generated
      by constructive nanolithography upon local electrochemical oxidation of the top 
      CH3 groups of a highly ordered OTS (n-octadecyltrichlorosilane) monolayer self
      assembled on silicon to -COOH (Adv. Mater. 2000, 12, 725-731). Retraction of such
      a patterned monolayer from a liquid that does not wet its nonpolar -CH3 surface
      (lyophobic) results in selective, site-defined immobilization of nanosized
      volumes of the liquid on the locally generated polar -COOH groups (lyophilic).
      Examples are given of WDSA of organic materials that offer further options for
      post-assembly chemical processing, such as nonvolatile low-melting olefins,
      acids, or thiols, the former being in situ reacted to generate polar functions
      like -COOH or -SH. Loading surface patterns created in this manner with silver or
      gold ions followed by further chemical processing results in elemental metal
      nanoparticles generated within the ion-binding organic material, which thus
      functions as a guiding template for planned metal deposition at predefined
      surface sites. WDSA is particularly versatile, as any nonvolatile material with
      appropriate melting temperature and surface wetting characteristics or solubility
      in a liquid displaying such properties may in principle be utilized to fabricate
      potentially useful surface nanostructures.

PMID- 17516685
TI  - Esomeprazole 20mg provides more effective intragastric Acid control than
      maintenance-dose rabeprazole, lansoprazole or pantoprazole in healthy volunteers.
AB  - OBJECTIVE: A high proportion of patients with gastro-oesophageal reflux disease
      experience recurrence of symptoms within a year of initial treatment. The key to
      preventing relapse is an effective maintenance therapy that maintains
      intragastric pH >4. This study was conducted to compare the effects on
      intragastric pH of maintenance doses of four proton pump inhibitors: esomeprazole
      20mg, lanso-prazole 15mg, rabeprazole 10mg and pantoprazole 20mg. STUDY
      PARTICIPANTS AND METHODS: Three standardised, randomised, two-way crossover
      studies were performed in a total of 108 Helicobacter pylori-negative healthy
      subjects. Intragastric pH was monitored on day 5 of once-daily oral dosing. The
      percentage of time of a 24-hour period with intragastric pH >4 and 24-hour median
      pH were measured on day 5. RESULTS: The mean percentage of time with intragastric
      pH >4 on day 5 was significantly longer following esomeprazole 20mg compared with
      either lansoprazole 15mg (esomeprazole 50.4% vs lansoprazole 43.0%, p = 0.026),
      rabeprazole 10mg (esomeprazole 59.8% vs rabeprazole 51.7%, p = 0.011) or
      pantoprazole 20mg (esomeprazole 59.6% vs pantoprazole 39.5%, p < 0.0001).
      CONCLUSIONS: Maintenance dose esomeprazole 20mg provided greater acid control and
      maintained intragastric pH >4 for a longer period of time than maintenance dose
      lansoprazole 15mg, rabeprazole 10mg and pantoprazole 20mg in healthy subjects.

PMID- 17516686
TI  - Effect of Carvedilol on QT Duration in Paediatric Patients with Congestive Heart
      Failure.
AB  - OBJECTIVE: To investigate the effect of carvedilol on electrocardiographic
      parameters in children with congestive heart failure. PATIENTS AND METHODS: 18
      children with heart failure (aged 2 months-17 years) were treated with carvedilol
      (initially 0.09 mg/kg/day, slowly increased up to 0.7 mg/kg/day) in addition to
      conventional therapy with digoxin, ACE inhibitors and diuretics. Twelve-lead rest
      electrocardiograms (ECGs) and echocardiography were performed in 16 patients with
      sinus rhythm at baseline and after 1, 2, 4 (n = 14) and 6 months (n = 14) of
      therapy. ECGs were analysed for heart rate, QT duration and QT dispersion.
      Echocardiography was performed for analysis of ejection fraction. RESULTS: After
      6 months of therapy the mean ejection fraction increased from 37% to 55% (p <
      0.05) and mean heart rate decreased by 14% (p < 0.05). Mean QT duration
      calculated by Bazett's formula (QT(B)) and Fridericia's formula (QT(F)) decreased
      from 428 msec (372-507 msec) to 387 msec (323-440 msec [QT(B)]; p < 0.05) and
      from 381 msec (315-466 msec) to 355 msec (309-435 msec [QT(F)]; p < 0.05)
      following therapy with carvedilol. In contrast, mean QT dispersion did not change
      significantly (18 msec; 10-40 msec before to 12 msec; 5-20 msec; p > 0.05).
      CONCLUSION: In conclusion, carvedilol treatment reduced QT duration but not QT
      dispersion in paediatric patients with heart failure. The decrease in QT duration
      reflects stabilisation of the action potential, and this may contribute to the
      improved prognosis in these patients.

PMID- 17516687
TI  - Long-Term Efficacy and Safety of Ipratropium Bromide plus Fenoterol via
      Respimat((R)) Soft Misttrade mark Inhaler (SMI) versus a Pressurised Metered-Dose
      Inhaler in Asthma.
AB  - OBJECTIVE: Respimat((R)) Soft Misttrade mark Inhaler (SMI) is a novel, propellant
      free device that significantly increases lung deposition compared with
      pressurised metered-dose inhalers (pMDIs). The aim of this study was to compare
      the efficacy and safety of ipratropium bromide/fenoterol hydrobromide (IB/FEN;
      Berodual((R))) delivered via Respimat((R)) SMI and via a chlorofluorocarbon (CFC)
      driven pMDI (CFC-MDI) in patients with asthma. DESIGN: Multicentre, randomised,
      double-blind, placebo-controlled, parallel- group study. PATIENTS: 631 patients
      (18-65 years old) with stable asthma. INTERVENTIONS: After a 2-week run-in period
      (IB/FEN 20mug/50mug via CFC-MDI, two actuations four times a day), patients were
      randomised to 12 weeks' treatment with one of five treatments: IB/FEN
      10mug/25mug, 20mug/50mug or placebo via Respimat((R)) SMI (one actuation four
      times a day), or IB/FEN 20mug/50mug or placebo via CFC-MDI (two actuations four
      times a day). The main efficacy measure was lung function (assessed on days 1,
      29, 57 and 85); safety was assessed by monitoring adverse events. RESULTS:
      Bronchodilator responses to IB/FEN were much greater than those to placebo (mean
      peak increases in forced expiratory volume in 1 second [FEV(1)] on day 85: 0.498
      0.521L, active treatment; 0.215 and 0.240L, placebo). According to the primary
      endpoint, i.e. the average change in FEV(1) from test-day baseline over the 6
      hours after dosing on day 85, neither IB/FEN dosage via Respimat((R)) SMI was
      inferior to IB/FEN via pMDI (p < 0.001). Non-inferiority of the two Respimat((R))
      SMI dosages was supported by analyses of other lung function measures, e.g.
      average change in FEV(1) from test-day baseline over the 6 hours after dosing on
      the other 3 test days, and peak FEV(1) on all test days. Overall, the safety
      profile of IB/FEN via Respimat((R)) SMI was comparable to that via CFC-MDI.
      CONCLUSION: IB/FEN from Respimat((R)) SMI is as effective and safe as from CFC
      MDI and enables a 2- to 4-fold daily dose reduction of IB/FEN.

PMID- 17516688
TI  - Ceftriaxone versus Other Antibiotics for Surgical Prophylaxis : A Meta-Analysis.
AB  - OBJECTIVE: To investigate possible differences in prophylaxis with ceftriaxone
      compared with other antimicrobial agents for surgical-site infections and remote
      infections such as respiratory tract infections (RTIs) and urinary tract
      infections (UTIs). METHODS: The efficacy of ceftriaxone was compared with that of
      other antibiotics in the perioperative prophylaxis of local (surgical wound) and
      remote (RTIs and UTIs) infections in a meta-analysis of randomised controlled
      trials published between 1984 and 2003. The analysis was based on a 2 x 2
      contingency table with classification by treatment and number of infections
      obtained from individual studies. RESULTS: Evaluations were performed on 48
      studies, for a total of 17 565 patients. Overall, 406 patients (4.8%) in the
      ceftriaxone group and 525 (6.3%) in the comparator group developed a surgical
      site infection (log odds ratio [OR] -0.30 [CI -0.50 to -0.13]; p < 0.0001). RTIs
      were observed in 292 (6.01%) patients in the ceftriaxone group and in 369 (7.6%)
      patients in the comparator group, (log OR -0.30 [CI -0.55 to -0.09]; p = 0.0013).
      UTIs were reported for 2.2% of the ceftriaxone prophylaxis patients compared with
      3.74% of the comparator group patients (log OR -0.54 [CI -1.18 to -0.16]; p <
      0.0001). Overall, in clean surgery 195 (5.1%) and 234 (6.2%) patients developed a
      surgical site infection in the ceftriaxone and comparator groups, respectively
      (log OR -0.22 [CI -0.51 to 0.01]; p = 0.0476). RTIs were prevented for all but
      1.57% of patients in the ceftriaxone group and 2.62% of patients in the
      comparator group (p = 0.01) in clean surgery, and for 9.54% of the ceftriaxone
      group versus 11.6% of the comparator group (p = 0.01) in clean-contaminated
      surgery. While results observed in clean surgery did not show statistically
      significant superiority of ceftriaxone in preventing UTI insurgence (log OR -0.21
      [CI 0.0-0.65]; p = 0.7702), this was clearly shown in the clean-contaminated
      surgery. In fact, 4.47% of patients in the ceftriaxone group versus 7.52% of
      patients in the comparator group developed a UTI (log OR -0.56 [CI -1.25 to 
      0.16]; p < 0.0001). Adverse events were observed in a similar proportion in the
      ceftriaxone prophylaxis and the comparator groups (0.35% and 0.23%,
      respectively). Duration of prophylaxis did not influence outcome of infection.
      CONCLUSIONS: The meta-analysis showed that ceftriaxone is statistically superior
      to other antibiotics in preventing both local and remote postoperative
      infections.

PMID- 17516689
TI  - Efficacy of low-dose tamsulosin on lower urinary tract symptoms suggestive of
      benign prostatic hyperplasia : a nonblind multicentre korean study.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of tamsulosin 0.2mg once
      daily in Korean patients with lower urinary tract symptoms (LUTS) suggestive of
      benign prostatic hyperplasia (BPH), who were treated for up to 1 year. MATERIALS
      AND METHODS: Of the 211 patients from six urology outpatient centres who
      participated in this investigation, 146 patients were evaluable. Tamsulosin 0.2
      mg/day was administered orally in a nonblind design for a 1-year period. The
      primary efficacy parameters were improvement in the total, obstructive and
      irritative International Prostate Symptom Score (IPSS), measured at baseline and
      at weeks 12, 24, 36 and 52, and in the maximal urinary flow rate (Qmax) measured
      at baseline and at weeks 24 and 52. The secondary efficacy parameters were a
      decrease of >/=30% in IPSS, and an increase in Qmax of >/=30% from baseline.
      Changes in parameters between baseline and 52 weeks were assessed using Student's
      paired t-test. RESULTS: Statistically significant, gradual improvements in all
      efficacy parameters were observed over the 1-year period. Tamsulosin 0.2 mg/day
      resulted in a mean reduction of 41.1% in total IPSS (p < 0.001) and a mean
      increase of 4.56 mL/sec in Qmax at 52 weeks (p < 0.001). Tamsulosin was well
      tolerated; adverse events occurred in 6.2% of patients and there were no
      withdrawals as a result of adverse events. There were no significant changes in
      blood pressure or pulse rate during the study. CONCLUSIONS: One-year treatment
      with tamsulosin 0.2 mg/day in Korean patients with suspected BPH was well
      tolerated and effective in improving LUTS and urinary flow. The effect on
      symptoms was apparent after 12 weeks of treatment, and symptom improvement was
      observed for up to 1 year.

PMID- 17516690
TI  - Oseltamivir distributes to influenza virus replication sites in the middle ear
      and sinuses.

PMID- 17516691
TI  - Survey of symptom burden in women with uncomplicated urinary tract infections.

PMID- 17516692
TI  - Impaired rehabilitation secondary to muscle weakness induced by meropenem.

PMID- 17516693
TI  - Safety and tolerability of volplex((r)) in elective surgery.
AB  - OBJECTIVE: Succinylated gelatin is widely used in the management of hypovolaemic
      conditions. Volplex((R)) is a new presentation of succinylated gelatin in a
      flexible, collapsible bag, which is sterilised at 121 degrees C. This study aimed
      to document the safety and tolerability of Volplex((R)), using Gelofusine((R)) as
      a control, in elective surgery. DESIGN AND PATIENTS: The study was a single
      centre, open-label, randomised, parallel-group trial that included patients aged
      18-75 years who were, in the opinion of the investigator, likely to need an
      infusion of a colloid as part of their surgical management. The patients were
      randomised to receive either Volplex((R)) or Gelofusine((R)) in a 2 : 1 ratio in
      favour of Volplex((R)). Three assessments, preoperative, perioperative and 24
      hours following anaesthetic induction, were performed. All statistical testing
      was two-sided and performed at a 5% level of significance. RESULTS: 76 patients
      (52 receiving Volplex((R)) and 24 receiving Gelofusine((R))) were included in the
      intent-to-treat population. The volumes of fluids infused were 1154mL and 1115mL
      for the Volplex((R)) and Gelofusine((R))groups, respectively, of which 962mL was
      Volplex((R)) and 958mL was Gelofusine((R)), respectively. Patients also received
      crystalloids and blood and there were no significant differences between groups
      in the amounts received. Eighteen Volplex((R)) recipients (35%) and 12
      Gelofusine((R)) recipients (50%) reported at least one adverse event. Of the 27
      events reported for Volplex((R)), 15 (56%) were considered not related and 12
      (44%) possibly related to Volplex((R)). In the case of Gelofusine((R)), 17 events
      were reported, and of these eight (47%) were considered not related and nine
      (53%) possibly related to Gelofusine((R)). None of the reported adverse events
      were considered probably related to either colloid. One serious adverse event,
      mild hypothermia, was reported in the Gelofusine((R)) group. The unexpected
      length of surgery was stated as the causal factor. There were no significant
      differences between Volplex((R)) and Gelofusine((R)) with regard to the number of
      patients with out-of-range laboratory values postoperatively. Urine output for
      both groups was reduced postoperatively, but there were no major differences
      between the groups observed. CONCLUSION: This small, open-label study showed that
      Volplex((R)), a new presentation of succinylated gelatin, was comparable to a
      well-established brand, Gelofusine((R))when used in the management of patients
      undergoing elective surgery.

PMID- 17516694
TI  - Oxybutynin extended release and tolterodine immediate release : a health economic
      comparison.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of a new extended-release (XL)
      formulation of oxybutynin relative to tolterodine immediate release (IR),
      currently the most prescribed treatment for overactive bladder in the UK.
      METHODS: A state-transition model was developed to compare outcomes over 1 year.
      Effectiveness and treatment persistence data were derived from the OBJECT
      (Overactive Bladder: Judging Effective Control and Treatment) study, a 3-month
      clinical trial comparing oxybutynin XL 10 mg/day with tolterodine IR 4 mg/day.
      The daily costs of oxybutynin XL and tolterodine IR were pound0.82 and pound1.04,
      respectively. These data and information from the literature were used to project
      outcomes beyond the trial time. Severity-specific incontinence cost profiles were
      developed for the UK (2002 costings). RESULTS: After 1 year, 3.1 more patients
      per 100 treated attained complete continence with oxybutynin XL compared with
      tolterodine IR, and 5.6% more had less than seven incontinent episodes per week.
      Over 1 year, patients receiving oxybutynin XL had almost 17 additional
      incontinence-free days and 95 fewer incontinent episodes. Estimated costs were
      pound86 lower per patient with oxybutynin XL. If drugs are priced equally,
      savings decrease to pound21 per patient. Oxybutynin XL maintains its advantage
      over wide ranges of inputs, and outcomes are similar if analyses are limited to 3
      months. CONCLUSION: Base-case analyses suggest that oxybutynin XL provides better
      effectiveness than tolterodine IR and reduces costs. Results indicate that
      oxybutynin XL is the dominant therapeutic option under a wide range of
      alternative inputs and assumptions.

PMID- 17516695
TI  - Safety and efficacy of oral nonsteroidal anti-inflammatory drugs in patients with
      rheumatoid arthritis : a six-month randomised study.
AB  - OBJECTIVE: To monitor the safety and efficacy profile of long-term treatment with
      diclofenac, nabumetone, meloxicam and celecoxib in patients with rheumatoid
      arthritis. DESIGN AND METHODS: This randomised, prospective clinical trial
      included a total of 461 subjects (313 females and 148 males) with clinically
      diagnosed rheumatoid arthritis. Their average age was 46.9 +/- 14.4 years (range
      20-69 years), and the average disease duration was 1333.7 +/- 992.85 days.
      Subjects were randomly assigned daily administration of one of the following:
      diclofenac 75-100mg, meloxicam 15mg, nabumetone 1000mg or celecoxib 200mg. During
      the 6-month treatment period, a monthly patient interview was conducted to
      evaluate drug efficacy and safety. RESULTS: 407 subjects successfully completed
      the 6-month treatment. Sixteen patients (12.2%) withdrew from the diclofenac
      group, 16 (12.2%) from the nabumetone group, 17 (11.8%) from the meloxicam group
      and five (9.1%) from the celecoxib group. Most withdrawals occurred during the
      first 3 months of treatment. Reasons for withdrawals in the first three groups
      were lack of efficacy (44.9%) and adverse effects (38.8%). For the celecoxib
      group, high cost (80%) was the main reason for withdrawal. Adverse drug reactions
      to NSAIDs mostly occurred at an early stage of treatment, with an incidence rate
      of 31.9% for the diclofenac group, 19.9% for the nabumetone group, 25.2% for the
      meloxicam group, and 7.27% for the celecoxib group. Clinical efficacy rates for
      the four NSAIDs were positively related to the length of treatment. During the
      first 4 months, diclofenac, meloxicam and celecoxib showed better efficacy than
      nabumetone. There were no significant differences in efficacy during the fifth
      and sixth months. The overall 6-month effectiveness rates were 68.8% for
      diclofenac, 59.8% for nabumetone, 67.6% for meloxicam and 69.1% for celecoxib.
      CONCLUSIONS: Adverse drug reactions and their related withdrawals occurred mostly
      at an early stage of NSAID treatment, so it is crucial to strengthen
      pharmacovigilance during this period. Among the investigated NSAIDs, celecoxib
      did not prove to be superior to diclofenac, nabumetone or meloxicam with respect
      to its efficacy in the treatment of rheumatoid arthritis; however, it did show
      good patient compliance and safety profiles.

PMID- 17516696
TI  - Short-term efficacy and safety of leflunomide in the treatment of active
      rheumatoid arthritis in everyday clinical use : open-label, prospective study.
AB  - OBJECTIVE: To determine the efficacy and safety profile of 6-month treatment with
      leflunomide 20mg daily in patients with acute rheumatoid arthritis (RA) receiving
      treatment from 197 office-based rheumatologists in France. METHODS: This open
      label, prospective, multicentre study included 378 ambulatory RA patients who
      received leflunomide at a loading dose of 100mg daily on days 1-3, followed by
      20mg daily for 6 months. The primary efficacy endpoint was a >/=20% response
      according to the American College of Rheumatology criteria (ACR 20) after 6
      months. Secondary efficacy criteria were a >/=50% response (ACR 50) and a >/=70%
      response (ACR 70), as well as disease activity score (DAS28) responses. RESULTS:
      Among the 407 selected patients, 378 patients were included in the study, all of
      whom were treated with leflunomide. Female patients made up 78.6% of the study
      population; the mean age was 57.7 +/- 12.0 years, and the mean disease duration
      was 9.7 +/- 8.5 years. At 6 months, the ACR 20 response rate was 48.2% (95%
      confidence interval [CI] 43-53%). ACR 50 and 70 response rates were 25.3% (95% CI
      21.0-30.1) and 11.7% (95% CI 8.6-15.4%), respectively. According to the DAS28,
      21.8% of patients had a good response, 39.9% a moderate response, and 38.2% were
      non-responders. The DAS28 response rate was thus 61.8% (95% CI 56.5-66.9%). Mean
      improvements in tender joint count were -5.6 +/- 7.4 (from baseline of 12.2 +/-
      6.7), in swollen joint count were -4.2 +/- 5.7 (from baseline of 9.8 +/- 5.8),
      and in investigator's global assessment of RA disease activity were -20.2 +/-
      25.1 (from baseline of 51.6 +/- 17.1). Treatment-related adverse events caused
      15.9% of patients to discontinue the study prematurely. Serious adverse events
      possibly related to therapy were reported in 2.4% of patients. CONCLUSIONS: This
      6-month study carried out under daily routine practice conditions in a typical
      sample of RA patients showed a favourable efficacy and safety profile for
      leflunomide 20mg daily. The study confirms the findings of the earlier phase II
      and III study programme in more selected patient samples.

PMID- 17516697
TI  - Steady-state pharmacokinetics of pravastatin in children with familial
      hypercholesterolaemia.
AB  - OBJECTIVE: To determine pharmacokinetic data for pravastatin in children, since
      current data are insufficient in this age group. SUBJECTS AND METHODS: A 2-week,
      multiple-dose, steady-state pharmacokinetic study was carried out with
      pravastatin 20mg daily in 24 children with familial hypercholesterolaemia (aged 8
      16 years; 12 prepubertal, 12 pubertal). A plasma concentration-time curve was
      performed on day 14. Pharmacokinetic curves for each individual were constructed
      using nonparametric methods, yielding area under the plasma concentration-time
      curve (AUC), maximum plasma concentration (C(max)) and half-life (t((1/2))).
      Clearance values and volumes of distribution were calculated from these
      parameters. Cholesterol lowering was observed on day 14 and 6 weeks after the
      start of pravastatin. RESULTS: The C(max) in prepubertal (group A) children (52.1
      +/- 27.0 mug/L [mean +/- SD]) differed, although not significantly (p = 0.09,
      unpaired two-tailed t-test), from the C(max) in adolescents (group B) [31.7 +/-
      29.2 mug/L]. There was a moderate negative correlation between C(max) and age
      (Spearman correlation r = -0.42; p = 0.04). The AUC in prepubertal children (91.3
      +/- 39.7 mug . h/L) did not differ significantly from the AUC in adolescents
      (69.3 +/- 57.0 mug . h/L). The t((1/2)) was the same for the two groups: 2.5 +/-
      1.1h. Clearance values (CL/f) varied widely between the two groups (group A: 4.3
      +/- 1.8 L/min; group B: 11.0 +/- 11.9 L/min; p = 0.08). A moderate positive
      correlation was found between clearance and age (Spearman correlation r = 0.36; p
      = 0.09). A large variation was found in the volumes of distribution within the
      two groups (group A: 31.2 mL/kg [SD 26.7], group B:37.0 mL/kg [SD 29.6]; p =
      0.12). A very weak positive correlation was found between age and volume of
      distribution (Spearman correlation r = 0.11; p = 0.61). A 27% low-density
      lipoprotein-cholesterol reduction from baseline was achieved at day 14.
      CONCLUSIONS: Body surface area and gender did not influence the pharmacokinetics
      of pravastatin in children aged 8-16 years. On the basis of our findings there
      are no reasons to use pravastatin at a dosage according to bodyweight or to use
      different dosage regimens from those in adults. However, for prepubertal children
      half the advised starting dose for adults may be sufficient.

PMID- 17516698
TI  - Tandospirone in the treatment of generalised anxiety disorder and mixed anxiety
      depression : results of a comparatively high dosage trial.

PMID- 17516699
TI  - Pharmacokinetics, preliminary efficacy and safety of subcutaneous melagatran and
      oral ximelagatran : a multicentre study of thromboprophylaxis in elective
      abdominal surgery.
AB  - OBJECTIVE: The oral direct thrombin inhibitor (oral DTI) ximelagatran and its
      active form, melagatran, which can be administered subcutaneously, were
      investigated for the prevention and treatment of thromboembolic complications.
      DESIGN AND PATIENTS: In this randomised, double-blind, double-dummy, parallel
      group study in patients (n = 90) undergoing general abdominal and/or pelvic
      surgery, 8-day and 35-day treatment regimens of postoperatively initiated sub
      cutaneous (sc) melagatran (3mg twice daily) followed by oral ximelagatran (24mg
      twice daily) were compared with standard-duration sc dalteparin (5000IU)
      initiated preoperatively. Pharmacodynamic and pharmacokinetic parameters,
      efficacy (number of patients with distal and/or proximal deep vein thrombosis
      [DVT] verified by bilateral venography on the final day of treatment) and safety
      were assessed. RESULTS: The pharmacokinetics of melagatran were well described by
      a one-compartment model with first-order absorption after administration of both
      sc melagatran and oral ximelagatran. Bioavailability of melagatran was 21% after
      the first oral dose of ximelagatran and was virtually unchanged throughout the
      study. Activated partial thromboplastin time increased in a non-linear manner
      with plasma melagatran concentration. The overall rate of DVT was 11.4% (8/70),
      with events distributed evenly between treatment groups. Bleeding volumes during
      surgery tended to be higher in the dalteparin group than in the
      melagatran/ximelagatran groups. Blood transfusion volumes and numbers of patients
      transfused were similar in all treatment groups. CONCLUSIONS: Good
      bioavailability of melagatran was achieved following oral administration of
      ximelagatran. Postoperative sc melagatran followed by oral ximelagatran appeared
      to be well tolerated, and the efficacy of standard-length or prolonged
      prophylaxis with sc melagatran and oral ximelagatran may be comparable to that of
      dalteparin initiated preoperatively.

PMID- 17516700
TI  - Efficacy and Safety of the Platelet-Activating Factor Receptor Antagonist BN
      52021 (Ginkgolide B) in Patients with Severe Sepsis : A Randomised, Double-Blind,
      Placebo-Controlled, Multicentre Trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the natural platelet-activating
      factor receptor antagonist, BN 52021 (ginkgolide B) in the treatment of patients
      with severe sepsis related to Gram-negative and mixed bacterial infection. DESIGN
      AND SETTING: Prospective, randomised, double-blind, placebo-controlled,
      multicentre study carried out in 13 academic medical intensive care centres in
      Germany with up to 14 patients per centre. PATIENTS: 88 patients with severe
      sepsis under standard medical and surgical care: nine patients with pure Gram
      positive infection, 79 patients with Gram-negative or mixed bacterial infections
      (subgroup for which efficacy was to be established). INTERVENTIONS: Patients were
      randomised to receive either placebo or BN 52021 1.25 mg/kg bodyweight
      intravenously every 12h over a 4-day period in addition to their standard medical
      and surgical care. MAIN OUTCOME MEASURES AND RESULTS: The primary efficacy
      variable was the 28-day all-cause mortality rate. The treatment groups were
      similar with respect to demographic data and prognostic factors influencing the
      outcome except for bodyweight and adequacy of antibiotic therapy. Analysis of
      patients with Gram-negative or mixed bacterial infection, for which efficacy was
      to be established, resulted in a 28-day all-cause mortality of 42.5% in the
      placebo group (n = 40; 17 deaths) versus 38.5% in the BN 52021 group (n = 39; 15
      deaths). Among all randomised patients, the 28-day all-cause mortality rate was
      40.9% in the placebo group (n = 44; 18 deaths) and 38.6% in the BN 52021 group (n
      = 44; 17 deaths). There were no differences in frequency and severity of adverse
      events between the two treatment groups. CONCLUSIONS: Four-day administration of
      BN 52021 failed to demonstrate a statistically significant reduction in mortality
      in patients with severe sepsis suspected or confirmed to be related to infections
      other than Gram-positive bacterial infection.

PMID- 17516701
TI  - Cotrimoxazole in the treatment of acute uncomplicated falciparum malaria in
      nigerian children : a controlled clinical trial.
AB  - OBJECTIVES: To evaluate the efficacy of cotrimoxazole in the treatment of
      Plasmodium falciparum malaria and to compare the efficacy of cotrimoxazole with
      that of pyrimethamine-sulfadoxine, a second-line antimalarial drug, in an area of
      high malaria transmission. PATIENTS AND METHODS: Children aged between 10 months
      and 10 years with clinical and parasitological evidence of P. falciparum malaria
      were randomised to receive either cotrimoxazole or pyrimethamine-sulfadoxine. 145
      children (73 and 72, respectively, in the cotrimoxazole and pyrimethamine
      sulfadoxine groups) completed the study per protocol and were evaluated. RESULTS:
      Pretreatment clinical and parasitological parameters were similar in the two
      treatment groups. The time to clear fever and other symptoms was similar in the
      two groups: 1.94 +/- 1.10 days versus 2.20 +/- 0.96 days, p > 0.05. Parasite
      clearance times were also similar: 2.62 +/- 0.91 days versus 2.94 +/- 1.17 days,
      respectively, for cotrimoxazole and pyrimethamine-sulfadoxine; p > 0.05. The cure
      rates on days 14, 21 and 28 were, respectively, 84.9, 75.3 and 74.0% for the
      cotrimoxazole group and 84.7, 80.5 and 75.0% for the pyrimethamine-sulfadoxine
      group. Both drugs were well tolerated. CONCLUSIONS: These results indicate that
      cotrimoxazole has similar efficacy to pyrimethamine-sulfadoxine in the treatment
      of acute uncomplicated P. falciparum malaria in children resident in an endemic
      area of Southwest Nigeria.

PMID- 17516703
TI  - Pancreotoxicity of Propofol Sedation during Purulent Meningitis : What is the
      Role for Octreotide?

PMID- 17516702
TI  - Depression during Pregnancy : Overview of Clinical Factors.
AB  - Depression during pregnancy is common, affecting an estimated 20% of women.
      However, conflicting data exist concerning the outcomes of this disorder. Thus,
      we reviewed studies that presented evidence for the use of antidepressants and
      those that examined untreated depression during the gestational period, in terms
      of clinical and epidemiological aspects.Observational studies have provided
      reassuring evidence of the safety of antidepressant use during pregnancy.
      However, due to the reluctance of healthcare providers to prescribe and patients
      to take medication during the obstetric period, approximately three-quarters of
      those diagnosed with depression remain untreated. Furthermore, healthcare
      providers apparently do not recognise the disorder in up to 50% of pregnant women
      who experience depression. Increased antidepressant dosing during pregnancy may
      be required to maintain euthymia; however, guidelines for effective dosing levels
      are absent. Consequently, many patients remain inadequately treated. Substantial
      maternal and fetal morbidity including substance abuse, functional impairment,
      increased risk of postnatal depression, and poor pregnancy outcomes have resulted
      from untreated depression.The consequences of those outcomes are likely to be
      associated with substantial clinical, social and economic burdens. An incidence
      based assessment of the consequences of prenatal depression would be useful in
      order to: (i) establish the impact on the quality of life of these patients and
      their families; (ii) assess the associated economic burden on individual families
      and the healthcare system; and (iii) to provide epidemiological data to enable
      the provision of suitable management strategies for these patients.

PMID- 17516704
TI  - Overview of the clinical pharmacokinetics of oxcarbazepine.
AB  - Oxcarbazepine (GP 47680, 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine- 5
      carboxamide) is an antiepileptic drug registered worldwide by Novartis under the
      trade name Trileptal((R)). Trileptal((R))is approved as adjunctive therapy or
      monotherapy for the treatment of partial seizures in adults and in children. In
      the US, Trileptal((R)) is approved as adjunctive therapy in adults and in
      children >/=4 years of age and as monotherapy in adults and in
      children.Trileptal((R))is currently marketed as 150, 300 and 600mg film-coated
      tablets for oral administration. A 60 mg/mL (6%) oral suspension formulation has
      also been registered worldwide.Oxcarbazepine and its pharmacologically active
      metabolite, 10-monohydroxy derivative (MHD; 10,11-dihydro-10-hydro-carbamazepine;
      GP 47779) show potent antiepileptic activity in animal models comparable to that
      of carbamazepine (Tegretol((R))) and phenytoin. Oxcarbazepine and MHD have been
      shown to exert antiepileptic activity by blockade of voltage-dependent sodium
      channels in the brain.Oxcarbazepine is rapidly reduced by cytosolic enzymes in
      the liver to MHD, which is responsible for the pharmacological effect of the
      drug. This step is mediated by cytosolic arylketone reductases. MHD is eliminated
      by conjugation with glucuronic acid. Minor amounts (4% of the dose) are oxidised
      to the pharmacologically inactive dihydroxy derivative (DHD). The absorption of
      oxcarbazepine is complete. In plasma after a single oral administration of
      oxcarbazepine the mean apparent elimination half-life (t((1/2))) of MHD in adults
      was 8-9h. Food has no effect on the bioavailability of the highest strength of
      the final market image tablet (600mg). At steady state MHD displays predictable
      linear pharmacokinetics at doses ranging from 300 to 2400mg. In children with
      normal renal function, renal clearance of MHD is higher than in adults, with a
      corresponding reduction in the terminal t((1/2)) of MHD. Consequently, although
      no special dose recommendation is needed, an increase in the dose of
      oxcarbazepine may be necessary to achieve similar plasma levels to those in
      adults. In patients with moderate to severe renal impairment (creatinine
      clearance <30 mL/min), the elimination t((1/2)) of MHD is prolonged with a
      corresponding 2-fold increase in area under the concentration-time curve.
      Therefore, a dose reduction of at least 50% and a prolongation of the titration
      period is necessary in these patients. Mild-to-moderate hepatic impairment does
      not affect the pharmacokinetics of MHD. Based on in vitro and in vivo findings
      and compared with antiepileptic drugs such as carbamazepine, phenytoin and
      phenobarbital, oxcarbazepine has a low propensity for drug-drug interactions. In
      vitro, MHD inhibits the cytochrome P450 (CYP) 2C19 (ki [inhibition constant] = 88
      micromol/L). At oxcarbazepine doses above 1.2g, a 40% increase in the
      concentration of phenytoin and a 15% increase in phenobarbital levels were
      observed. Oxcarbazepine/MHD at high doses may slightly increase phenobarbital and
      phenytoin plasma concentrations. Therefore, when using high doses of
      oxcarbazepine an adjustment in the dose of phenytoin may be required. In vitro,
      MHD is only a weak inducer of uridine diphospate (UDP)-glucuronyltransferase
      (UDPGT) and therefore is unlikely to have an effect on drugs that are mainly
      eliminated by conjugation through the UDPGT enzymes (e.g. valproic acid and
      lamotrigine). Weak interactions between MHD and antiepileptic drugs that are
      strong inducers of CYP enzymes have been identified. Carbamazepine, phenobarbital
      and phenytoin have been shown to reduce MHD levels by 30-40% when coadministered
      with oxcarbazepine, with no decrease in efficacy. Oxcarbazepine decreases the
      plasma hormone levels (ethinylestradiol and levonorgestrel) of oral
      contraceptives and may therefore have the potential to cause oral contraception
      failure.

PMID- 17516705
TI  - Psychometric validation of the italian translation of the gastrointestinal
      symptom-rating scale and quality of life in reflux and dyspepsia questionnaire in
      patients with gastro-oesophageal reflux disease.
AB  - BACKGROUND: Symptoms of heartburn and their impact on health-related quality of
      life (HR-QOL) are often evaluated in clinical trials. When a questionnaire is
      translated into a new language, a linguistic validation is necessary but not
      sufficient unless the psychometric characteristics have been verified. OBJECTIVE:
      To document the psychometric characteristics of the Italian translation of the
      Gastrointestinal Symptom-Rating Scale (GSRS) and Quality of Life in Reflux and
      Dyspepsia (QOLRAD) questionnaire. PATIENTS AND METHODS: 152 consecutive patients
      with symptoms of heartburn (mean +/- SD age 46.5 +/- 16.2 years; 40.1% males)
      completed the Italian translation of GSRS, the heartburn version of QOLRAD, the
      36-item Short-Form health survey (SF-36), and the Hospital Anxiety and Depression
      (HAD) scale. RESULTS: The internal consistency reliability of GSRS ranged from
      0.62 to 0.76 and of QOLRAD from 0.77 to 0.89. The relevant domains of the GSRS
      ('Reflux', 'Abdominal Pain' and 'Indigestion') and QOLRAD domain scores
      significantly correlated. GSRS domains 'Reflux' and 'Abdominal Pain' strongly
      correlated (negatively) with most of the domains of the SF-36. Similarly, all
      QOLRAD domains significantly correlated with all SF-36 domains. CONCLUSION: The
      psychometric characteristics of the Italian translations of GSRS and QOLRAD were
      found to be good, with satisfactory reliability and validity.

PMID- 17516706
TI  - Regression of microalbuminuria in type 2 diabetics after switch to irbesartan
      treatment : an observational study in 38 016 patients in primary care.
AB  - OBJECTIVE: This study aimed to assess the blood pressure-lowering potency,
      renoprotective efficacy and safety of the angiotensin II type 1 (AT(1))-receptor
      blocker irbesartan in monotherapy or in combination with hydrochlorothiazide or
      other antihypertensive medications in patients with type 2 diabetes mellitus
      switched from various antihypertensive pretreatments. DESIGN AND METHODS:
      Multicentre, open, prospective, 6-month observational study in 38 016 patients at
      9838 general practitioners' offices throughout Germany. Microalbuminuria in type
      2 diabetics was measured with semiquantitative immunological Micral-II urine
      dipstick tests. MAIN OUTCOME MEASURE: Proportion of patients with albuminuria at
      baseline and at 3 and 6 months. Analysis of adverse events. RESULTS: The study
      population consisted of an equal number of males and females, mean body mass
      index was 28.4 kg/m(2), and mean glycosylated haemoglobin (HbA(1c)) was 7.2%.
      After the switch to irbesartan (in 86% of patients to the 300mg dosage in mono-
      or combination therapy), mean systolic/diastolic blood pressure was decreased by
      23/12mm Hg. Irbesartan treatment over 6 months reduced the proportion of patients
      with microalbuminuria from 49.2 to 23.2% (relative reduction: 52.8%; p < 0.05)
      and the rate of patients with macroalbuminuria from 6.0 to 4.4% (relative
      reduction: 26.7%; p < 0.05). The renoprotective effect of irbesartan was
      consistent in various subgroups (analyses by sex, weight, diabetes duration,
      insulin treatment, strength of blood pressure-lowering effect, and
      antihypertensive pretreatment). Tolerability was excellent: 99.6% of patients
      remained free of any adverse events during the study. CONCLUSION: The profound
      blood pressure-lowering and renoprotective effect of irbesartan in type 2
      diabetes documented in clinical endpoint studies was confirmed in second-line
      therapy in a large sample of primary-care patients. Furthermore, in patients
      switched from previous ACE-inhibitor therapy, the renoprotective effect of
      irbesartan was of the same magnitude as in the total cohort.

PMID- 17516707
TI  - Comparison of Lornoxicam and Rofecoxib in Patients with Activated Osteoarthritis
      (COLOR Study).
AB  - BACKGROUND AND OBJECTIVE: Impaired mobility and pain mean a loss of quality of
      life for patients with rheumatic diseases. Therefore the initial aim of therapy
      is rapid and efficient analgesia in order to achieve the best possible result for
      these patients. Lornoxicam is a strong analgesic and anti-inflammatory NSAID with
      balanced cyclo-oxygenase (COX)-1/COX-2 inhibition and excellent tolerability. In
      the course of the development of selective COX-2 inhibitors, it was maintained
      that COX-2 inhibitors decrease the risk of injury to the upper gastrointestinal
      (GI) tract with a similar efficacy to that of classic NSAIDs. However, a clinical
      trial comparing both substances has never been performed. In the present study we
      investigated the treatment of patients with osteoarthritis with lornoxicam in
      comparison with treatment with the selective COX-2 inhibitor rofecoxib. This
      multicentre clinical investigation focused on efficacy and tolerability. PATIENTS
      AND METHODS: A total of 2520 patients (most of them with osteoarthritis) were
      treated over 25 days on average. Before and after treatment patients documented
      their individual scores for pain on movement, at rest and during the night, and
      their individual duration of morning stiffness as well as the consequent grade of
      restriction. At the end of the study all individuals involved judged the efficacy
      and safety of the therapy. RESULTS: All improvements in each efficacy parameter
      were clinically relevant in each treatment group and significantly superior (p <
      0.001) in the lornoxicam group. Pain on movement (-45.3%), at rest (-42.0%) and
      at night (-42.5%) was reduced by rofecoxib, whereas improvements after treatment
      with lornoxicam exceeded those effects significantly (-55.8%, -55.8% and -59.9%,
      respectively). Shortening of the duration of morning stiffness was significantly
      (p < 0.001) more pronounced with lornoxicam (-66.6%) than with rofecoxib (
      50.2%). Nearly three times as many patients discontinued rofecoxib treatment
      because of lack of efficacy compared with lornoxicam treatment (8.9% versus
      3.4%). Physicians judged lornoxicam to be markedly superior to rofecoxib, since
      excellent efficacy was observed in 40.9% of all cases versus 20.1% with
      rofecoxib. Serious adverse events did not occur. Adverse events were reported in
      5.4% of all lornoxicam patients compared with 12.0% of the rofecoxib recipients
      (p < 0.001). GI symptoms showed a slight trend of being less frequent following
      rofecoxib therapy. CONCLUSIONS: The results of this study confirmed the efficacy
      and safety of both drugs. Lornoxicam and rofecoxib are effective in the treatment
      of patients with activated osteoarthritis; the analgesic and anti-inflammatory
      effects of lornoxicam are significantly superior to those of rofecoxib without
      inferiority in tolerability.

PMID- 17516708
TI  - Ketoprofen for add-on pain treatment to paracetamol after strabismus surgery in
      children.
AB  - OBJECTIVE: To evaluate whether combining ketoprofen, a nonsteroidal anti
      inflammatory analgesic, with paracetamol would provide better postoperative
      analgesia than paracetamol alone in children undergoing strabismus surgery. STUDY
      DESIGN: A prospective, double-blind, randomised clinical trial. PATIENTS AND
      METHODS: 56 generally healthy children, aged 3-15 years, undergoing strabismus
      surgery with standardised endotracheal anaesthesia were randomly assigned to
      receive either ketoprofen 1 mg/kg intravenously or normal saline at induction of
      anaesthesia and a second dose 3h later. All children received paracetamol 24
      mg/kg solution orally 60 min before surgery and fentanyl 2 mug/kg intravenously
      during surgery. For rescue analgesia during the first 6h children in pain (pain
      score >3 on an 11-point scale: 0 = no pain, 10 = worst possible pain) received
      fentanyl 1 mug/kg intravenously. Any episodes of vomiting and all other adverse
      events were recorded for the first 24h. RESULTS: 21 of 27 children in the
      ketoprofen-paracetamol group (78%) and 23 of 29 in the paracetamol group (79%)
      received fentanyl for rescue analgesia. The mean (SD) number of fentanyl doses
      during the first 6h was 1.2 (0.9) in the ketoprofen-paracetamol group and 1.7
      (1.1) doses in the paracetamol group (mean difference 0.5 doses; 95% CI for
      difference: -0.1, 1.3; p = 0.11). Eight (30%) vomited in the ketoprofen
      paracetamol group and 14 in the paracetamol group (48%) [difference 19%; 95% CI 
      6, 44; p = 0.15). No serious adverse events occurred. CONCLUSION: Neither
      paracetamol nor ketoprofen-paracetamol provided sufficient analgesia for children
      after strabismus surgery because most needed rescue analgesia.

PMID- 17516709
TI  - Tacrolimus in heart transplant recipients: an overview.
AB  - The development of cyclosporine was pivotal in allowing cardiac transplantation
      to become an accepted treatment for patients with end-stage heart disease. More
      recently, tacrolimus has become available as a useful alternative to
      cyclosporine, and has been successfully combined with either azathioprine or the
      newer anti-proliferative agents, mycophenolate mofetil or sirolimus. Numerous
      randomized clinical trials have demonstrated that tacrolimus is comparable to
      cyclosporine in terms of overall patient survival and at least equally effective
      in preventing acute rejection. In addition, tacrolimus has been particularly
      effective as a rescue treatment in cases where recurrent rejection has occurred
      with cyclosporine. The adverse effects of tacrolimus differ from those of
      cyclosporine, and the drug particularly shows an improved profile with respect to
      hypertension, dyslipidemia, and long-term renal function. These data have
      recently led to the regulatory approval of tacrolimus for primary
      immunosuppression in patients undergoing cardiac transplantation in the US.

PMID- 17516711
TI  - Pharmacological chaperones in nephrogenic diabetes insipidus: possibilities for
      clinical application.
AB  - The antidiuretic hormone arginine-vasopressin regulates water homeostasis in the
      human body by binding to its vasopressin type 2 receptor (V2R). Mutations in
      AVPR2, the gene encoding V2R, lead to the X-linked congenital form of nephrogenic
      diabetes insipidus (NDI), a disease characterized by the inability to concentrate
      urine in response to vasopressin; often this involves missense mutations or
      deletion of one or a few amino acids. In vitro V2R expression studies revealed
      that the function of most of these receptors is not disturbed, but due to their
      misfolding, the quality control mechanism of the endoplasmic reticulum (ER)
      retains these receptors inside the cell, thereby preventing their functioning at
      the plasma membrane. This review summarizes our current knowledge on ER retention
      of V2R mutants, and describes the different approaches that have been undertaken
      to restore the plasma membrane expression and function of V2R mutants in NDI in
      vitro and in vivo. The use of cell permeable receptor ligands (called
      'pharmacological chaperones') appears promising for the treatment of NDI in a
      subset of patients.

PMID- 17516710
TI  - Epitope mapping: the first step in developing epitope-based vaccines.
AB  - Antibodies are an effective line of defense in preventing infectious diseases.
      Highly potent neutralizing antibodies can intercept a virus before it attaches to
      its target cell and, thus, inactivate it. This ability is based on the
      antibodies' specific recognition of epitopes, the sites of the antigen to which
      antibodies bind. Thus, understanding the antibody/epitope interaction provides a
      basis for the rational design of preventive vaccines. It is assumed that
      immunization with the precise epitope, corresponding to an effective neutralizing
      antibody, would elicit the generation of similarly potent antibodies in the
      vaccinee. Such a vaccine would be a 'B-cell epitope-based vaccine', the
      implementation of which requires the ability to backtrack from a desired antibody
      to its corresponding epitope. In this article we discuss a range of methods that
      enable epitope discovery based on a specific antibody. Such a reversed
      immunological approach is the first step in the rational design of an epitope
      based vaccine. Undoubtedly, the gold standard for epitope definition is x-ray
      analyses of crystals of antigen:antibody complexes. This method provides atomic
      resolution of the epitope; however, it is not readily applicable to many antigens
      and antibodies, and requires a very high degree of sophistication and expertise.
      Most other methods rely on the ability to monitor the binding of the antibody to
      antigen fragments or mutated variations. In mutagenesis of the antigen, loss of
      binding due to point modification of an amino acid residue is often considered an
      indication of an epitope component. In addition, computational combinatorial
      methods for epitope mapping are also useful. These methods rely on the ability of
      the antibody of interest to affinity isolate specific short peptides from
      combinatorial phage display peptide libraries. The peptides are then regarded as
      leads for the definition of the epitope corresponding to the antibody used to
      screen the peptide library. For epitope mapping, computational algorithms have
      been developed, such as Mapitope, which has recently been found to be effective
      in mapping conformational discontinuous epitopes. The pros and cons of various
      approaches towards epitope mapping are also discussed.

PMID- 17516712
TI  - Rho GTPase/Rho kinase inhibition as a novel target for the treatment of glaucoma.
AB  - Rho kinase (ROCK1 and ROCK2) is a serine/threonine kinase that serves as an
      important downstream effector of Rho GTPase, and plays a critical role in
      regulating the contractile tone of smooth muscle tissues in a calcium-independent
      manner. Several lines of experimental evidence indicate that modulating ROCK
      activity within the aqueous humor outflow pathway using selective inhibitors
      could achieve very significant benefits for the treatment of increased
      intraocular pressure in patients with glaucoma. The rationale for such an
      approach stems from experimental data suggesting that both ROCK and Rho GTPase
      inhibitors can increase aqueous humor drainage through the trabecular meshwork,
      leading to a decrease in intraocular pressure. In addition to their ocular
      hypotensive properties, inhibitors of both ROCK and Rho GTPase have been shown to
      enhance ocular blood flow, retinal ganglion cell survival and axon regeneration.
      These properties of the ROCK and Rho GTPase inhibitors indicate that targeting
      the Rho GTPase/ROCK pathway with selective inhibitors represents a novel
      therapeutic approach aimed at lowering increased intraocular pressure in glaucoma
      patients.

PMID- 17516713
TI  - Proteomics of blood-based therapeutics: a promising tool for quality assurance in
      transfusion medicine.
AB  - Blood-based therapeutics are cellular or plasma components derived from human
      blood. Their production requires appropriate selection and treatment of the donor
      and processing of cells or plasma proteins. In contrast to clearly defined,
      chemically synthesized drugs, blood-derived therapeutics are highly complex
      mixtures of plasma proteins or even more complex cells. Pathogen transmission by
      the product as well as changes in the integrity of blood constituents resulting
      in loss of function or immune modulation are currently important issues in
      transfusion medicine. Protein modifications can occur during various steps of the
      production process, such as acquisition, enrichment of separate components (e.g.
      coagulation factors, cell populations), virus inactivation, conservation, and
      storage. Contemporary proteomic strategies allow a comprehensive assessment of
      protein modifications with high coverage, offer capabilities for qualitative and
      even quantitative analysis, and for high-throughput protein identification.
      Traditionally, proteomics approaches predominantly relied on two-dimensional gel
      electrophoresis (2-DE). Even if 2-DE is still state of the art, it has inherent
      limitations that are mainly based on the physicochemical properties of the
      proteins analyzed; for example, proteins with extremes in molecular mass and
      hydrophobicity (most membrane proteins) are difficult to assess by 2-DE. These
      limitations have fostered the development of mass spectrometry centered on non
      gel-based separation approaches, which have proven to be highly successful and
      are thus complementing and even partially replacing 2-DE-based approaches.
      Although blood constituents have been extensively analyzed by proteomics, this
      technology has not been widely applied to assess or even improve blood-derived
      therapeutics, or to monitor the production processes. As proteomic technologies
      have the capacity to provide comprehensive information about changes occurring
      during processing and storage of blood products, proteomics can potentially guide
      improvement of pathogen inactivation procedures and engineering of stem cells,
      and may also allow a better understanding of factors influencing the
      immunogenicity of blood-derived therapeutics. An important development in
      proteomics is the reduction of inter-assay variability. This now allows the
      screening of samples taken from the same product over time or before and after
      processing. Optimized preparation procedures and storage conditions will reduce
      the risk of protein alterations, which in turn may contribute to better recovery,
      reduced exposure to allogeneic proteins, and increased transfusion safety.

PMID- 17516714
TI  - Certolizumab pegol: in Crohn's disease.
AB  - Certolizumab pegol is a pegylated humanized Fab' fragment of an anti-tumor
      necrosis factor-alpha (TNFalpha) monoclonal antibody, which binds with high
      affinity to both membrane-bound and soluble TNFalpha and demonstrates high
      neutralizing potency for these factors. The elimination half-life of certolizumab
      in humans has been extended to approximate/= 2 weeks through pegylation, allowing
      subcutaneous administration of this agent once every 4 weeks. Subcutaneous
      certolizumab pegol 400mg once every 4 weeks (with an additional 400mg dose at
      week 2) was effective as induction and maintenance therapy in patients with
      moderate to severe Crohn's disease in whom baseline serum C-reactive protein
      levels were >/=10 mg/L, according to data from two well designed, randomized
      phase III trials. Certolizumab pegol was, in general, well tolerated, and adverse
      events associated with the drug were of a mild to moderate nature; no instances
      of lupus were reported in any of the trials.

PMID- 17516717
TI  - Recombinant full-length parathyroid hormone (1-84): profile report.

PMID- 17516718
TI  - Cost Effectiveness of Controlled-Release Oxybutynin Compared with Immediate
      Release Oxybutynin and Tolterodine in the Treatment of Overactive Bladder in the
      UK, France and Austria.
AB  - OBJECTIVE: To estimate the cost effectiveness of controlled-release (CR)
      oxybutynin compared with immediate-release (IR) oxybutynin and tolterodine in the
      treatment of overactive bladder (OAB) in Austria, France and the UK. DESIGN AND
      SETTING: This was a modelling study on the management of patients with OAB who
      were >/=18 years of age, and had urge or mixed incontinence with a primary-urge
      component. The study was performed from the perspective of payers (i.e. the
      National Health Service [NHS] in the UK, Social Security in France and the Sick
      Funds in Austria) and patients. METHODS: Clinical outcomes attributable to
      managing OAB were obtained from the published literature, and resource
      utilisation estimates were derived from a panel of clinicians. Using decision
      analytical techniques, three decision models were constructed depicting the
      management of OAB with CR oxybutynin, IR oxybutynin and tolterodine over 6 months
      in the UK, France and Austria. The models were used to estimate the cost
      effectiveness of CR oxybutynin relative to the other two anticholinergic drugs in
      each of the three countries and the expected direct patient costs and indirect
      societal costs (at 2000/2001 prices). MAIN OUTCOME MEASURES AND RESULTS: Starting
      OAB treatment with CR oxybutynin instead of either IR oxybutynin or tolterodine
      in the UK and Austria was found to be a potentially dominant strategy, since it
      improves clinical outcome at a lower cost, from the payers' perspective. In
      France, starting OAB treatment with CR oxybutynin instead of either the IR
      formulation or tolterodine was found to be a potentially cost-effective strategy
      from the payer's perspective. The expected 6-monthly direct costs to patients
      were euro230, euro720-920 and euro970-1000 in the UK, France and Austria,
      respectively. In the UK and Austria, these costs were broadly consistent between
      initial treatments. However, in France, tolterodine-treated patients would be
      expected to incur 28% more expenditure than patients treated with the other two
      drugs. Transportation emerged as the primary cost driver, accounting for at least
      60% of patients' out-of-pocket expenditure, in all three countries. Irrespective
      of the initial treatment, patients would be expected to miss 1-2 days of work
      over 6 months as a result of their OAB. This equates to an expected lost
      productivity cost of euro84, euro250 and euro98 in the UK, France and Austria,
      respectively. CONCLUSION: Starting OAB treatment with CR oxybutynin is expected
      to be a clinically more effective strategy than starting with either IR
      oxybutynin or tolterodine, and potentially the most cost-effective strategy in
      all three countries.

PMID- 17516719
TI  - Lack of Interaction between Modified-Release Fluvastatin and Amlodipine in
      Healthy Subjects.
AB  - OBJECTIVE: To investigate the potential for a pharmacokinetic interaction between
      fluvastatin modified-release 80mg tablet (Lescol((R)) XL; fluvastatin XL) and
      amlodipine 5mg tablet (Norvasc((R))) following multiple once-a-day doses for 2
      weeks. DESIGN: This was a single-centre, six-sequence, three-period, randomised,
      crossover design study. Fluvastatin XL 80mg tablet and amlodipine 5mg tablet were
      administered once a day for 2 weeks either alone or in combination. Fluvastatin
      and amlodipine serum concentration profiles were characterised on day 14 for each
      treatment. The pharmacokinetic interaction between the two drugs was evaluated
      based on the p-values and 90% confidence intervals (CIs) for log-transformed
      highest observed concentration (C(max)), area under the plasma concentration-time
      curve calculated by the linear trapezoidal method up to 24 hours (AUC(24)), and
      apparent oral clearance at steady state (CL/F), using a single entity as the
      reference treatment and the combination as the test treatment. Adverse events
      (AEs), safety laboratory tests and physical examinations were evaluated for
      safety. STUDY PARTICIPANTS: Twenty-four healthy subjects were enrolled and 19
      completed the study. The safety analysis was based on data from all 24 subjects
      who received at least one dose of a treatment, while the pharmacokinetic analysis
      was based on data from the 19 subjects who completed all treatments. RESULTS: The
      coadministration of fluvastatin XL and amlodipine resulted in no significant
      changes in the steady-state AUC (469 vs 454 mug . h/L), C(max) (96 vs 89 mug/L),
      and CL/F (197 vs 232 L/h) of fluvastatin when compared with fluvastatin XL alone.
      The p-values for these comparisons were between 0.172 and 0.238, and the 90% CIs
      for the geometric means were within 78% and 139%. A similar comparison for
      amlodipine showed no significant difference in the steady-state AUC (132 vs 140
      mug . h/L), C(max) (7.1 vs 7.5 mug/L) and CL/F (41 vs 40 L/h) of amlodipine. The
      p-values for these comparisons were between 0.309 and 0.353, and the 90% CIs for
      the geometric means were within 90% and 111%. The majority of the AEs were mild
      in severity. There were no clinically relevant changes in clinical laboratory
      results, physical examinations or vital sign parameters. CONCLUSION: There were
      no significant differences in the steady-state pharmacokinetics of fluvastatin or
      amlodipine when they were administered together and the small differences
      observed were not clinically relevant. Therefore, no dose adjustment of either
      drug is necessary when fluvastatin and amlodipine are coadministered.

PMID- 17516720
TI  - Weekly oral alendronic Acid in male osteoporosis.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of alendronic acid 70mg once
      weekly for the treatment of male osteoporosis. PATIENTS AND METHODS: This
      randomised, double-blind, placebo-controlled, 12-month trial compared the effect
      of alendronic acid 70mg once weekly or placebo (randomised 2 : 1) on bone mineral
      density (BMD) in 167 men with spine or hip BMD at least 2 standard deviations
      (SD) below the mean for young normal white males or nontraumatic fracture. All
      patients received calcium and vitamin D (colecalciferol). We measured lumbar
      spine, hip and total body BMD, and biochemical markers of bone turnover.
      Fractures were collected as adverse events. RESULTS: Alendronic acid 70mg once
      weekly produced significant BMD increases from baseline of 4.3% at the spine,
      2.1% at the femoral neck, 2.4% at the trochanter, and 1.4% at the total body,
      which were all significantly greater than placebo (p < 0.05). The increase at the
      lumbar spine was significant relative to baseline and placebo after 6 months of
      treatment (p < 0.001). The treatment effect was consistent regardless of BMD,
      age, height, weight, body mass index (BMI) and hypogonadal status at baseline.
      Alendronic acid significantly decreased biochemical markers of bone turnover
      relative to baseline and placebo. Alendronic acid was generally well tolerated,
      with an incidence of gastrointestinal adverse events similar to placebo.
      CONCLUSION: Alendronic acid 70mg administered once weekly is an effective and
      convenient alternative to daily dosing for the treatment of male osteoporosis.

PMID- 17516721
TI  - Medical outcomes of glaucoma therapy from a nationwide representative survey.
AB  - OBJECTIVE: To evaluate the medical outcomes of patients treated for primary open
      angle glaucoma (POAG) or ocular hypertension. PATIENTS AND METHODS: Sixty-eight
      ophthalmologists selected at random from a national professional list in France
      were asked to report on disease progression in consecutive patients who they saw
      in their clinics and who had either POAG, normal tension glaucoma/ocular
      hypertension, and who were aged >18 years of age. Data on sociodemographics,
      general and ocular comorbidities, glaucoma risk factors, visual acuity (VA),
      optic nerve head (ONH) clinical data, and visual fields were collected. Disease
      progression was defined as a deterioration of ONH and/or visual field since
      initial diagnosis. Changes in treatment were also monitored. A treatment change
      was defined as adding a new drug or changing any of the current treatments. Time
      to treatment failure was compared using the Wilcoxon test applied to survival
      curves. RESULTS: Of 127 patients who were evaluated, 12 developed a disease
      progression after diagnosis (average follow-up 2.4 years). No statistically
      significant difference in the known confounding factors of disease progression
      was found between patients with or without disease progression. At 32 months,
      2.6% of the patients with no changes in treatment had a DP, compared with 22.6%
      with one change in treatment and 46.2% with two or more changes in treatment (p <
      0.03). Patients who experienced adverse effects (p < 0.008) and those who said
      they were unhappy with their treatment (p < 0.03) more often experienced disease
      progression. CONCLUSION: An estimated 9.4% of a representative sample of patients
      with POAG or ocular hypertension experienced disease progression within 2.5 years
      of initial diagnosis. Patients with disease progression had more changes in
      treatment and adverse events; they were also more likely to have complained about
      being unhappy with their treatment.

PMID- 17516723
TI  - Improvement in Discomfort and Decreased Blood Flow Associated with Severe
      Arterial Wall Calcification following Etidronic Acid.

PMID- 17516722
TI  - Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine,
      Methylsulfonylmethane and their Combination in Osteoarthritis.
AB  - OBJECTIVE: Glucosamine, classified as a slow-acting drug in osteoarthritis
      (SADOA), is an efficacious chondroprotective agent. Methylsulfonylmethane (MSM),
      the isoxidised form of dimethyl-sulfoxide (DSMO), is an effective natural
      analgesic and anti-inflammatory agent. The aim of this study was to compare the
      efficacy and safety of oral glucosamine (Glu), methylsulfonylmethane (MSM), their
      combination and placebo in osteoarthritis of the knee. PATIENTS AND DESIGN: A
      total of 118 patients of either sex with mild to moderate osteoarthritis were
      included in the study and randomised to receive either Glu 500mg, MSM 500mg, Glu
      and MSM or placebo capsules three times daily for 12 weeks. Patients were
      evaluated at 0 (before drug administration), 2, 4, 8 and 12 weeks post-treatment
      for efficacy and safety. The efficacy parameters studied were the pain index, the
      swelling index, visual analogue scale pain intensity, 15m walking time, the
      Lequesne index, and consumption of rescue medicine. RESULTS: Glu, MSM and their
      combination significantly improved signs and symptoms of osteoarthritis compared
      with placebo. There was a statistically significant decrease in mean (+/- SD)
      pain index from 1.74 +/- 0.47 at baseline to 0.65 +/- 0.71 at week 12 with Glu (p
      < 0.001). MSM significantly decreased the mean pain index from 1.53 +/- 0.51 to
      0.74 +/- 0.65, and combination treatment resulted in a more significant decrease
      in the mean pain index (1.7 +/- 0.47 to 0.36 +/- 0.33; p < 0.001). After 12
      weeks, the mean swelling index significantly decreased with Glu and MSM, while
      the decrease in swelling index with combination therapy was greater (1.43 +/-
      0.63 to 0.14 +/- 0.35; p < 0.05) after 12 weeks. The combination produced a
      statistically significant decrease in the Lequesne index. All treatments were
      well tolerated. CONCLUSION: Glu, MSM and their combination produced an analgesic
      and anti-inflammatory effect in osteoarthritis. Combination therapy showed better
      efficacy in reducing pain and swelling and in improving the functional ability of
      joints than the individual agents. All the treatments were well tolerated. The
      onset of analgesic and anti-inflammatory activity was found to be more rapid with
      the combination than with Glu. It can be concluded that the combination of MSM
      with Glu provides better and more rapid improvement in patients with
      osteoarthritis.

PMID- 17516724
TI  - Cost effectiveness of memantine in moderately severe to severe Alzheimer's
      disease : a markov model in Finland.
AB  - BACKGROUND: In patients with moderately severe to severe Alzheimer's disease, the
      N-methyl-D-aspartate (NMDA) antagonist memantine has been shown to improve
      outcomes and to be associated with reductions in resource utilisation and total
      healthcare costs relative to no pharmacological intervention after 28 weeks in
      phase III clinical and pharmacoeconomic studies. However, the longer term cost
      implications of treatment with memantine are not known. OBJECTIVE: To evaluate
      the effect of treatment with memantine in patients with moderately severe to
      severe Alzheimer's disease on resource use and on cost and patient outcomes in
      Finland over a 5-year time horizon. METHODS: A Markov model was constructed to
      simulate a patient's progression through a finite series of health states with a
      time horizon of 5 years. The states were defined in terms of physical dependency,
      place of residency (community or institution), and cognitive function. Each 6
      month Markov cycle was repeated ten times. A 5% rate was used to discount costs.
      Inputs for the model were derived from epidemiological data collected during the
      Kuopio 75+ Study, a Finnish population-based health survey of dementia and
      functional capacity among in-dividuals aged >/=75 years. Costs were considered
      from a societal perspective. Probabilities used in the model, together with cost
      and resource use differences between treatment with memantine (Ebixa((R)),
      Namenda((R)), Axura((R))) and no pharmacological intervention, were derived from
      a randomised, double-blind, placebo-controlled clinical trial that included an
      economic assessment. This study enrolled 252 patients with moderately severe to
      severe Alzheimer's disease. We took a conservative approach that assumed that the
      effectiveness of treatment with memantine was limited to 12 months' duration.
      Monte Carlo simulations were performed to evaluate the effect of treatment with
      memantine on duration of independence and time to institutionalisation.
      Sensitivity analyses included memantine efficacy best- (5 years) and worst- (6
      months) case scenarios, and an analysis in which 5% discounting was not applied.
      RESULTS: Memantine therapy was associated with approximately 4 extra months of
      independence, 1 additional month of residence in the community, and a cost
      reduction relative to placebo of approximately euro1700 per patient over 5 years,
      despite the limiting of persistence of efficacy to 12 months (year of costing,
      2001). Monte Carlo simulations and sensitivity analyses supported the findings.
      CONCLUSION: According to the model, over 5 years the additional drug costs of
      treating patients with moderately severe to severe Alzheimer's disease with
      memantine were amply offset by cost savings related chiefly to increased
      independence and delayed institutionalisation.

PMID- 17516725
TI  - Efficacy and safety of Ibuprofen arginine in the treatment of primary
      dysmenorrhoea.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of
      ibuprofen arginate in the treatment of patients with primary dysmenorrhoea in
      normal clinical practice. STUDY DESIGN: In this open trial, patients received an
      initial oral dose of ibuprofen arginine 600mg at the onset of pain, followed by
      the same dose every 6 hours, if necessary, with a maximum daily dose of 2400mg.
      The study assessed the evolution of pain intensity, rapidity of action, need for
      supplementary analgesics, decrease in working or school hours lost, and safety
      and tolerability of ibuprofen arginine treatment. Each patient was evaluated
      prior to inclusion in the study and after one and three cycles. RESULTS: From the
      1093 recruited patients, 854 women were evaluable for safety and tolerability,
      and 838 for efficacy. Significant improvement in pain relief was observed 15
      minutes after treatment compared with baseline values (p < 0.001). At 15 and 30
      minutes the percentage of patients reporting a marked decrease in pain intensity
      was 82.2% and 97.6%, respectively. Additionally, a significant reduction in
      absenteeism from work or school (from a mean of 4.6-0.8 hours per cycle) was
      observed (p < 0.001). Thirty-eight patients presented with adverse events in the
      trial period, but only 26 subjects (3% of 854) in the adverse events cohort
      reported having a possible adverse event, with gastrointestinal complaints being
      the most frequent. CONCLUSION: Ibuprofen arginine appears to be effective, fast,
      safe and well tolerated in the treatment of patients with primary dysmenorrhoea.

PMID- 17516726
TI  - Effect of influenza treatment with oseltamivir on health outcome and costs in
      otherwise healthy children.
AB  - OBJECTIVE: To evaluate the effect of treating children with influenza with
      oseltamivir on health outcomes and costs to healthcare payers. PATIENTS AND
      DESIGN: Health outcome data from the oseltamivir paediatric clinical development
      programme plus data from the literature were used in an economic model developed
      to predict morbidity and mortality due to influenza and its specified
      complications. Published data on the cost of care in the UK were used to compare
      oseltamivir with usual care in children aged 1-12 and 1-5 years by estimating
      cost-effectiveness and cost-utility ratios. RESULTS: Oseltamivir reduced median
      time to return to normal health and activity by almost 2 days (40% reduction,
      67.1 vs 111.7 hours; p < 0.0001) versus placebo. In children aged 1-5 years, a
      48% reduction (63.5 vs 121.3 hours; p = 0.0003) was observed. Oseltamivir-treated
      children who developed otitis media returned to normal health and activity 30%
      faster (99.6 vs 141.5 hours; p = 0.0517) than the placebo group. In the economic
      model, oseltamivir in the base-case analysis (assuming 60% diagnostic accuracy,
      full compliance, and 100% receive and start treatment within 48 hours, standard
      discounting according to the UK National Institute of Clinical Excellence
      guidelines) resulted in favourable cost-utility ratios in children aged both 1-12
      and 1-5 years, with incremental cost-utility rates of L11 173/quality-adjusted
      life year (QALY) and oseltamivir being dominant compared with usual care,
      respectively (year of costing, 2002). Even in conservative scenarios, most cost
      utility ratios remained <L30 000/QALY. CONCLUSIONS: Oseltamivir is an effective
      treatment for children with influenza, allowing faster return to normal health
      and activity compared with usual care. From the healthcare payer perspective,
      oseltamivir is a potentially cost-effective strategy for otherwise healthy
      children.

PMID- 17516727
TI  - Cost-analysis of relapsing-remitting multiple sclerosis in Italy after the
      introduction of new disease-modifying agents.
AB  - BACKGROUND AND OBJECTIVE: During the last decade, several agents have proven to
      be effective in the treatment of relapsing-remitting multiple sclerosis (RRMS),
      for example interferon-beta (IFNbeta) and glatiramer acetate. This study aimed to
      perform a cost-analysis of the treatment of patients with RRMS in Italy after the
      introduction of these new agents. STUDY DESIGN: This was a retrospective
      observational study with systematic patient inclusion. METHODS AND RESULTS: Data
      gathered from 630 patients with confirmed RRMS over a 2-year period were
      evaluated. Overall, the direct cost over 2 years reached ?11 073 100 thousand,
      corresponding to a per-patient cost of ?17 576 (year of costing, 2001). The cost
      of disease-modifying agents represented approximately 77% of the total
      expenditure. IFNbeta accounted for 94% of the expense of disease-modifying
      agents, corresponding to a 2-year cost per patient of ?20 223. Although
      glatiramer acetate and immunoglobulins were also associated with a high level of
      expense, these were prescribed in only 3.8% and 1.1% of patients, respectively.
      Using regression analyses, IFNbeta therapy, disability, number of days spent in
      hospital per year and the frequency of magnetic resonance imaging procedures were
      the main predictors of total costs. CONCLUSION: Based on the results of this
      study, IFNbeta treatment considerably modified the management of RRMS and was
      associated with a rise in cost of treatment per patient.

PMID- 17516729
TI  - Verrucous psoriasis in a patient with chronic C hepatitis treated with
      interferon.

PMID- 17516728
TI  - Hypersensitivity to nadroparin calcium : case report and review of the
      literature.

PMID- 17516730
TI  - Intraepithelial lymphocytosis in architecturally normal small intestinal mucosa:
      association with morbid obesity.

PMID- 17516732
TI  - Medical examiners, coroners, and public health.

PMID- 17516734
TI  - Follicular tumors of the thyroid.

PMID- 17516736
TI  - Periadventitial fat.

PMID- 17516737
TI  - The origin of reference intervals.
AB  - CONTEXT: Standards have been developed for establishing reference intervals, but
      little is known about how intervals are determined in practice, interlaboratory
      variation in intervals, or errors that occur while setting reference intervals.
      OBJECTIVES: To determine (1) methods used by clinical laboratories to establish
      reference intervals for 7 common analytes, (2) variation in intervals, and (3)
      factors that contribute to establishment of "outlier" intervals. DESIGN: One
      hundred sixty-three clinical laboratories provided information about their
      reference intervals for potassium, calcium, magnesium, thyroid-stimulating
      hormone, hemoglobin, platelet count, and activated partial thromboplastin time.
      RESULTS: Approximately half the laboratories reported conducting an internal
      study of healthy individuals to validate reference intervals for adults. Most
      laboratories relied on external sources to establish reference intervals for
      pediatric patients. There was slight variation in intervals used by the central
      80% of study laboratories, but some laboratories outside the central 80% had
      surprisingly low and high limits for their reference intervals. In some cases the
      intervals used by 2 laboratories had no overlap. For example, one laboratory
      considered a hemoglobin of 13.8 g/dL in a woman to be "low" while another
      considered the same value to be "high." Three percent of reference intervals
      contained a limit that qualified as an "outlier" using standard statistical
      tests; we could not identify any practice associated with adoption of outlier
      intervals. CONCLUSIONS: Many laboratories adopt reference intervals from
      manufacturers without on-site testing of healthy individuals. Reference intervals
      used by facilities that forgo on-site testing are not statistically different
      from intervals validated with on-site studies.

PMID- 17516739
TI  - Diagnosis of prostatic carcinoma after therapy.
AB  - CONTEXT: Prostate cancer is the most common cancer of men in the United States
      and is third only to lung and colon cancer as a cause of cancer death. In 2006,
      27,350 Americans will die of prostate cancer, and 234,460 new cases will be
      diagnosed. Treatment changes in the benign and cancerous prostate create
      diagnostic challenges in pathologic interpretation, particularly in needle biopsy
      specimens and in evaluation of extraprostatic metastases. OBJECTIVE: To summarize
      therapy-related pathologic findings in the prostate with emphasis on recognition
      of treated adenocarcinoma. DATA SOURCES: Extensive review of published literature
      and the authors' experience. CONCLUSIONS: Following therapy for prostate cancer,
      it is critical that the clinician provide the pertinent history of androgen
      deprivation or radiation therapy to assist the pathologist in rendering the
      correct diagnosis.

PMID- 17516740
TI  - The endometrium.
AB  - CONTEXT: Endometrial tissue specimens are commonly encountered in daily practice.
      It is well known that a number of problematic diagnostic scenarios occur relative
      to these specimens. OBJECTIVE: To emphasize practical aspects of endometrial
      specimen handling and reporting, with selected comments on common diagnostic
      pitfalls, including (1) the diagnosis of endometrial intraepithelial carcinoma in
      atrophic endometrial biopsy specimens, (2) evaluation of adequacy of endometrial
      sampling specimens, (3) problems in diagnosing and measuring the depth of
      myometrial invasion in endometrial carcinoma, (4) the question of metastasis
      versus independent primaries in concurrent carcinomas of endometrium and one or
      both ovaries, (5) the problematic differential diagnoses between type 1
      (primarily endometrioid) and type 2 (primarily serous) adenocarcinomas, and (6)
      atypical hyperplasia and proposed classification systems for its replacement.
      DATA SOURCES: Published literature, consensus statements, and personal
      experience. CONCLUSIONS: A systematic approach to the handling and reporting of
      endometrial specimens reduces the potential for omission and error. Recognition
      of diagnostic pitfalls and practical approaches to their resolution help improve
      quality.

PMID- 17516741
TI  - Small lymphoid proliferations in extranodal locations.
AB  - CONTEXT: Low-grade non-Hodgkin lymphomas frequently involve extranodal sites
      including the gastrointestinal tract, skin, and lung, either selectively or as
      part of widespread dissemination. Differentiation from inflammatory or infectious
      conditions requires knowledge of specific histologic characteristics of the
      various entities as well as ancillary techniques. OBJECTIVE: To describe the key
      features and provide diagnostic clues to the identification of specific
      extranodal low-grade lymphomas of T-cell and B-cell types including small
      lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, extranodal
      marginal zone B-cell lymphomas of mucosal-associated lymphoid tissue, and hairy
      cell leukemia. Histologic and cytologic features are highlighted, as well as
      appropriate integration of results of ancillary diagnostic studies including flow
      cytometry, immunohistochemistry, molecular features, and cytogenetics. DATA
      SOURCES: The published literature as well as personal experience from a
      specialized hematopathology practice at a large university medical center.
      CONCLUSIONS: Correct identification of extranodal low-grade lymphomas and
      differentiation from hyperplastic and inflammatory or infectious processes
      require the ability to distinguish each of the specific entities discussed.
      Ancillary studies are often indispensable in reaching a correct diagnosis.

PMID- 17516742
TI  - Glioblastoma.
AB  - CONTEXT: Glioblastoma (GBM), the most common primary intracranial malignancy, is
      a morphologically diverse neoplasm with dismal prognosis despite multimodality
      therapy. Only 3 distinct morphologic variants of GBM are currently recognized by
      the current World Health Organization classification scheme, including GBM, giant
      cell GBM, and gliosarcoma. Additional variants, some of which have significant
      morphologic overlap with tumors that have more favorable prognosis and treatment
      response rates, particularly anaplastic oligodendroglioma, have been described
      since its publication in 2000 and may be included in the next classification.
      OBJECTIVE: To summarize the morphologic and molecular genetic diversity of both
      well-established and novel GBM variants and outline our approach to these
      heterogeneous neoplasms and their distinction from other diffuse, high-grade
      gliomas. DATA SOURCES: Published literature and our own experience in an active
      academic diagnostic surgical neuropathology practice were reviewed. CONCLUSIONS:
      Precise subclassification of GBM is required for accurate prognostication and
      appropriate treatment planning.

PMID- 17516743
TI  - Transbronchial biopsy interpretation in the patient with diffuse parenchymal lung
      disease.
AB  - CONTEXT: The most common lung tissue samples seen by pathologists worldwide are
      obtained with the flexible bronchoscope. Specimens taken for examination of
      diffuse or multifocal parenchymal lung abnormalities pose special challenges for
      the general surgical pathologist, and these challenges are often compounded by
      high clinical expectations for accurate and specific diagnosis. OBJECTIVE: To
      present and discuss the most common histopathologic patterns and diagnostic
      entities seen in transbronchial biopsy specimens in the setting of diffuse or
      multifocal lung disease. Specifically, acute lung injury, eosinophilic pneumonia,
      diffuse alveolar hemorrhage, chronic cellular infiltrates, organizing pneumonia,
      alveolar proteinosis, sarcoidosis, Wegener granulomatosis, intravenous drug abuse
      related microangiopathy, Langerhans cell histiocytosis, and
      lymphangioleiomyomatosis are presented. Clinical and radiologic context is
      provided for the more specific diagnostic entities. DATA SOURCES: The published
      literature and experience from a consultation practice. CONCLUSIONS: The
      transbronchial biopsy specimen can provide valuable information for clinical
      management in the setting of diffuse or multifocal lung disease. Computed
      tomographic scans are useful for selecting appropriate patients to undergo biopsy
      and in limiting the differential diagnosis. Knowledge of the clinical context,
      radiologic distribution of abnormalities, and histopathologic patterns is
      essential. With this information, the surgical pathologist can substantially
      influence the diagnostic workup and help guide the clinician to an accurate
      clinical/radiologic/pathologic diagnosis.

PMID- 17516744
TI  - Epithelioid cell clusters with an extensive lymphoid background.
AB  - CONTEXT: Fine-needle aspiration of salivary gland lesions can be particularly
      challenging for pathologists. There are numerous neoplasms that occur in this
      area and several cytologic variations of each specific lesion. OBJECTIVE: To
      present and discuss a practical pattern recognition approach to fine-needle
      aspiration diagnosis, which includes categorizing lesions that share a certain
      overall cytologic architectural pattern, followed by identifying unique cellular
      characteristics that are specific to a certain lesion. An extensive discussion of
      one cytologic common pattern of salivary gland lesions, "epithelioid cell
      clusters with an extensive lymphoid background," is presented. The pathologic
      entities that fall under this architectural pattern group are discussed, with an
      emphasis on neoplasms. DATA SOURCES: Published literature and personal
      experience. CONCLUSIONS: A practical cytologic architectural pattern method can
      aid the pathologist in rendering a correct diagnosis when evaluating salivary
      gland lesions. One common pattern in salivary gland cytopathology is epithelioid
      cell clusters with an extensive lymphoid background. This pattern is often
      associated with Warthin tumor; however, other benign and malignant entities fall
      under this diagnostic group. Unique cytologic features separate these lesions
      into their respective diagnostic category.

PMID- 17516745
TI  - Selected diagnostic problems in neoplastic dermatopathology.
AB  - CONTEXT: Selected cutaneous neoplasms share features with benign counterparts or
      have subtle morphologic features that could be overlooked by the pathologist.
      OBJECTIVE: To present clues to the diagnosis of potentially deceptive
      malignancies, including desmoplastic malignant melanoma, nevoid malignant
      melanoma, subcutaneous lymphoma, metastatic breast carcinoma, and epithelioid
      sarcoma. DATA SOURCES: Published literature and personal experience. CONCLUSIONS:
      Knowledge of commonly misdiagnosed cutaneous neoplasms will help the general
      surgical pathologist avoid these potential pitfalls in neoplastic
      dermatopathology.

PMID- 17516746
TI  - Histopathology of serrated adenoma, its variants, and differentiation from
      conventional adenomatous and hyperplastic polyps.
AB  - CONTEXT: Serrated adenomas can be morphologically subdivided into traditional and
      sessile types. They are thought to have a comparable rate of cancer progression
      like conventional adenomas, but they potentially have a faster rate of growth
      through methylation pathway(s). They share similar morphologic features with both
      the conventional adenoma and the hyperplastic polyp in a fashion that is
      different from a mixed adenoma and a hyperplastic polyp. OBJECTIVE: To describe
      the histopathologic features of traditional serrated adenoma and sessile serrated
      adenoma and their comparison with traditional adenomas and hyperplastic polyp.
      DATA SOURCES: Relevant articles in peer-review journals and the authors' working
      experience as practicing surgical pathologists with a specific interest in
      gastrointestinal pathology. CONCLUSIONS: Both types of serrated adenomas,
      traditional serrated adenoma and sessile serrated adenoma, are morphologically
      distinct, clinically important entities, and they can be diagnosed accurately in
      routine practice.

PMID- 17516747
TI  - Recurring translocation (10;17) and deletion (14q) in clear cell sarcoma of the
      kidney.
AB  - CONTEXT: Clear cell sarcoma of the kidney (CCSK) is a prognostically unfavorable
      renal neoplasm of childhood. Previous cytogenetic studies of CCSK have reported
      balanced translocations t(10;17)(q22;p13) and t(10;17)(q11;p12). Although the
      tumor suppressor gene p53 is located at the chromosome 17p13 breakpoint, p53
      abnormalities are rarely present in these tumors. OBJECTIVE: To identify
      cytogenetic abnormalities in CCSK and correlate these findings with other
      clinicopathologic parameters. DESIGN: A retrospective review of CCSK patients
      from 1990 to 2005 was conducted at our medical center. We performed clinical and
      histologic review, p53 immunohistochemical and classic cytogenetics (or ploidy
      analysis), and p53 fluorescence in situ hybridization analyses. RESULTS: Five
      male patients (age range, 6 months to 4 years) were identified with cytogenetic
      abnormalities. Of 3 cytogenetically informative cases, one revealed a clonal
      balanced translocation t(10;17)(q22;p13) and an interstitial deletion of
      chromosome 14, del(14)(q24.1q31.1), and the other 2 patients had normal
      karyotypes. Fluorescence in situ hybridization for p53 in the t(10;17) case
      revealed no deletion. Immunohistochemical evaluation of p53 demonstrated lack of
      nuclear protein accumulation in all cases. CONCLUSIONS: Together with the
      published literature, our results indicate that translocation (10;17) and
      interstitial deletions of chromosome 14q are recurring cytogenetic lesions in
      CCSK. To date, 3 cases of CCSK or "sarcomatoid Wilms tumors" have been reported
      to exhibit t(10;17). One previously reported case of CCSK contained deletion 14q.
      Results of p53 immunohistochemistry and/or p53 fluorescence in situ hybridization
      in this report suggest lack of mutations or deletions of this tumor suppressor in
      these CCSK cases. The t(10;17) breakpoint and deletion of chromosome 14q24
      suggest that other genes are involved in tumor pathogenesis.

PMID- 17516748
TI  - Anti-interleukin 8 autoantibody:interleukin 8 immune complexes visualized by
      laser confocal microscopy in injured lung.
AB  - CONTEXT: Anti-interleukin 8 autoantibody:interleukin 8 (anti-IL-8 autoantibody:IL
      8) complexes are present in lung fluids of patients with acute lung injury/acute
      respiratory distress syndrome (ALI/ARDS), and levels of these complexes correlate
      with progression to and the outcome of ARDS. Fc gammaRIIa, an immunoglobulin G
      (IgG) receptor, mediates proinflammatory activity of the complexes. OBJECTIVE: To
      evaluate lung tissues from patients with ARDS for presence of anti-IL-8
      autoantibody:IL-8 complexes and to establish whether the complexes associate with
      Fc gammaRIIa. DESIGN: Lung tissue sections from 3 patients with ARDS and sections
      of normal lung tissues from 3 patients were stained with antibodies against IL-8
      and IgG to detect immune complexes and with antibody against Fc gammaRIIa. In
      some experiments, sections were blocked with anti-Fc gamma RIIa antibody before
      staining. Samples were analyzed using confocal microscopy. RESULTS: Interleukin 8
      costained with IgG and Fc gammaRIIa in lung tissues from patients with ARDS but
      not in control tissues, suggesting that anti-IL-8 autoantibody:IL-8 complexes are
      deposited in lungs of patients with ARDS via Fc gammaRIIa. Further,
      colocalization between IL-8 and Fc gammaRIIa could be blocked by anti-Fc
      gammaRIIa. CONCLUSIONS: Our data demonstrate that anti-IL-8 autoantibody:IL-8
      complexes are present in lung tissues of patients with ARDS, and are attached to
      Fc gammaRIIa.

PMID- 17516749
TI  - Comparison of ataxia-telangiectasia mutated protein expression in diffuse large B
      cell lymphomas of primary central nervous system and non-central nervous system
      origin.
AB  - CONTEXT: The ataxia-telangiectasia mutated (ATM) gene encodes a nuclear 370-kd
      phosphoprotein known to be associated with chromosomal regions containing double
      strand breaks. The mutations in the ATM gene may be involved in the development
      of some subtypes of sporadic lymphomas and leukemias. In primary central nervous
      system diffuse large B-cell lymphomas (PCNS DLBCLs), the pathogenetic role of ATM
      mutation has not been investigated. OBJECTIVE: To investigate ATM protein
      expression in PCNS DLBCLs, in comparison with that in non-central nervous system
      (non-CNS) DLBCLs and to study the relationship of ATM protein loss with several
      clinicopathologic parameters. DESIGN: This study included 42 cases of PCNS DLBCL
      and 33 cases of non-CNS DLBCL from immunocompetent patients. The ATM protein loss
      was analyzed by immunohistochemical staining. For the subclassification of DLBCL
      and analysis of the relationship between ATM and other prognostic markers, we
      performed immunohistochemical evaluation to detect the following markers: Bcl-6,
      CD10, multiple myeloma-1, CD138, Bcl-2, Ki-67, and p53. RESULTS: The loss of ATM
      expression was statistically more frequent in PCNS DLBCLs (21/42 cases [50.0%])
      than in non-CNS DLBCLs (0/33 cases [0.0%]; P < .001). The loss of ATM expression
      was not a prognostic marker in PCNS DLBCLs (P = .64). The loss of ATM expression
      had a strong correlation with the germinal center B-cell-like subtype (P = .01),
      a low Ki-67 labeling index (P = .03), and low Bcl-2 expression (P = .01) among
      several clinicopathologic parameters. CONCLUSIONS: Our results suggest that the
      ATM protein is more strongly correlated with PCNS DLBCL lymphomagenesis than with
      non-CNS DLBCLs, especially in germinal center B-cell-like subtypes demonstrating
      low Ki-67 labeling indexes and low Bcl-2 expression.

PMID- 17516750
TI  - Measuring the clinical impact of pathologist reviews of blood and body fluid
      smears.
AB  - CONTEXT: Despite the widespread practice of pathologist review of blood and body
      fluid smears, little is known about its impact on improving patient care.
      OBJECTIVE: To assess the clinical usefulness of pathologist review of blood and
      body fluid smears. DESIGN: Survey study. Pathology residents contacted the
      ordering physician after pathologist reviews were reported to assess their
      clinical impact. RESULTS: Ninety-six pathologist reviews met criteria for study
      inclusion, and 64 ordering physicians were successfully contacted during the 2
      month study period. Of the 64 cases, 19 reviews (30%) had been seen by the
      physician within 24 to 48 hours after the report was issued and 33 (51%) had not
      been seen; in 4 (6%) instances, physicians did not remember whether they had seen
      the review. Eight reviews (13%) were considered urgent enough to warrant
      immediate communication by the pathologist. Of the 27 reviews that were seen or
      directly communicated, 23 (85%) contributed to clinical diagnosis and/or patient
      management. CONCLUSIONS: This study demonstrates the contribution of pathologist
      reviews of blood and body fluids to clinical diagnosis and patient management.
      The results also highlight the problem of a lack of physician awareness of
      clinical pathology results.

PMID- 17516751
TI  - The impact of amino-terminal pro-brain natriuretic peptide testing on hospital
      length of stay and morbidity in patients with acute decompensated heart failure.
AB  - CONTEXT: In clinical trials, N-terminal pro-brain natriuretic peptide (NT-proBNP)
      testing has been shown to be valuable for diagnosis and triage of patients with
      acute decompensated heart failure. It is not yet clear what benefits might be
      expected from the initiation of NT-proBNP testing in an everyday clinical
      setting. OBJECTIVE: To determine the effects of NT-proBNP testing on hospital
      length of stay as well as on 60-day morbidity and mortality in patients with
      acute decompensated heart failure before and after the test was implemented in
      the clinical laboratory. DESIGN: We measured hospital length of stay and 60-day
      morbidity and mortality rates among patients with acute decompensated heart
      failure admitted before and after initiation of NT-proBNP testing in our
      hospital. Differences in demographics between preimplementation and
      postimplementation groups were compared with the chi2 test for categorical
      variables and the Wilcoxon rank sum test for continuous variables. Comparison
      between the hospital length of stay for each group was evaluated using the Mann
      Whitney U test. Differences in rates of rehospitalization or death at 60 days
      following presentation were assessed using chi2 cross-tabulation. RESULTS:
      Patients in the postimplementation group had similar clinical features as those
      in the preimplementation group. The hospital length of stay for patients in the
      postimplementation study group decreased both with respect to mean (1.86-day
      reduction) and median (1.3-day reduction) hospital stay (both, P = .03).
      Additionally, significantly lower rates of death (6.6% absolute risk reduction, P
      = .01), rehospitalization (12.1% absolute risk reduction, P = .005), and the
      composite of the 2 rates (18.7% absolute risk reduction, P = .008) were found
      following initiation of NT-proBNP testing. CONCLUSIONS: Implementation of NT
      proBNP testing may result in significant reductions in hospital length of stay as
      well as improvements in rates of morbidity and mortality in patients with acute
      decompensated heart failure.

PMID- 17516752
TI  - Diminished need for folate measurements among indigent populations in the post
      folic acid supplementation era.
AB  - CONTEXT: The mandated fortification of processed grains with folic acid in the
      United States and Canada in 1998 was intended to reduce the incidence of neural
      tube defects in pregnant women. The incidence of folate deficiency in most
      populations has declined dramatically since then. OBJECTIVE: To determine the
      rate of folate deficiency in a cohort of indigent patients, a population among
      those at highest risk for folate deficiency. DESIGN: Using data from 3 years
      (1997, 2000, and 2004), we examined results of laboratory tests for red blood
      cell folate ordered at 3 hospitals that predominately service the needs of
      indigent patients. Folate concentration cutoffs were 160 ng/mL (363.6 nmol/L) and
      94 ng/mL (213 nmol/L). RESULTS: Using a red blood cell folate cutoff
      concentration of 160 ng/mL (363.6 nmol/L), the combined incidence of folate
      deficiency decreased from 4.8% in 1997 to 0.6% in 2004. At a cutoff of 94 ng/mL
      (213 nmol/L), the incidence went from 0.98% to 0.09% in 1997 and 2004,
      respectively. Even when the folate concentration was found to be low, the
      majority of these subjects did not have macrocytosis. CONCLUSIONS: These data
      suggest that folate deficiency has become a rare event in the United States, and
      the utility of routine folate measurements for patients with anemia and/or
      increased mean corpuscular volume are difficult to justify.

PMID- 17516753
TI  - The role of periadventitial fat in atherosclerosis.
AB  - CONTEXT: It has become increasingly evident that adipose tissue is a
      multifunctional organ that produces and secretes multiple paracrine and endocrine
      factors. Research into obesity, insulin resistance, and diabetes has identified a
      proinflammatory state associated with obesity. Substantial differences between
      subcutaneous and omental fat have been noted, including the fact that omental fat
      produces relatively more inflammatory cytokines. Periadventitial fat, as a
      specific adipose tissue subset, has been overlooked in the field of
      atherosclerosis despite its potential diagnostic and therapeutic implications.
      OBJECTIVE: To review (1) evidence for the role of adventitial and periadventitial
      fat in vessel remodeling after injury, (2) the relationship between adventitial
      inflammation and atherosclerosis, (3) the association between periadventitial fat
      and plaque inflammation, and (4) the diagnostic and therapeutic implications of
      these roles and relationships for the progression of atherosclerosis. DATA
      SOURCES: We present new data showing greater uptake of iron, administered in the
      form of superparamagnetic iron oxide, in the periadventitial fat of
      atherosclerotic mice than in control mice. In addition, macrophage density in the
      periadventitial fat of lipid-rich plaques is increased compared with
      fibrocalcific plaques. CONCLUSIONS: There is a striking paucity of data on the
      relationship between the periadventitial fat of coronary arteries and
      atherosclerosis. Greater insight into this relationship might be instrumental in
      making strides into the pathophysiology, diagnosis, and treatment of coronary
      artery disease.

PMID- 17516754
TI  - Alveolar soft part sarcoma.
AB  - This article provides an overview of the pathology of alveolar soft part sarcoma,
      focused on its morphology, special stains useful in diagnosis, and the clinical
      and radiographic features of the disease. Alveolar soft part sarcoma is a rare
      neoplasm of unknown histogenesis with poor prognosis. Although there are several
      immunohistochemical stains available to help reach the diagnosis, the morphology
      of the tumor should be considered the main diagnostic feature. The periodic acid
      Schiff stain is the best single stain that supports the diagnosis.

PMID- 17516756
TI  - Genetic and environmental bases of childhood antisocial behavior: a multi
      informant twin study.
AB  - Genetic and environmental influences on childhood antisocial and aggressive
      behavior (ASB) during childhood were examined in 9- to 10-year-old twins, using a
      multi-informant approach. The sample (605 families of twins or triplets) was
      socioeconomically and ethnically diverse, representative of the culturally
      diverse urban population in Southern California. Measures of ASB included symptom
      counts for conduct disorder, ratings of aggression, delinquency, and psychopathic
      traits obtained through child self-reports, teacher, and caregiver ratings.
      Multivariate analysis revealed a common ASB factor across informants that was
      strongly heritable (heritability was .96), highlighting the importance of a
      broad, general measure obtained from multiple sources as a plausible construct
      for future investigations of specific genetic mechanisms in ASB. The best fitting
      multivariate model required informant-specific genetic, environmental, and rater
      effects for variation in observed ASB measures. The results suggest that parents,
      children, and teachers have only a partly "shared view" and that the additional
      factors that influence the "rater-specific" view of the child's antisocial
      behavior vary for different informants. This is the first study to demonstrate
      strong heritable effects on ASB in ethnically and economically diverse samples.

PMID- 17516757
TI  - Sex differences in the causes of self-reported adolescent delinquency.
AB  - Sex differences in the causes of self-reported adolescent delinquency were
      examined in full and half siblings born to a nationally representative sample of
      women in the United States. Qualitative sex differences in the genes that
      influence delinquency were not detected. Similarly, the proportions of variance
      in both aggressive and nonaggressive delinquency attributable to genetic and
      environmental influences did not differ significantly between girls and boys.
      Nonetheless, total variance in delinquency was greater among boys, and a scalar
      sex-differences model suggested that genetic and environmental influences on
      delinquency have less effect on population variation in delinquency among girls.
      Similarly, a test of the polygenic multiple threshold model suggested that girls
      require greater causal liability for the expression of delinquency than boys.

PMID- 17516758
TI  - Inattention as a key predictor of tobacco use in adolescence.
AB  - The authors examined the prediction from inattention to tobacco use among 2
      cohorts (ages 7 and 13) of a community sample followed to young adulthood.
      Changes in self-reported tobacco use were tested with marginal transitional
      regression models, using parent and teacher ratings of inattention, hyperactivity
      impulsivity, and other psychopathology, along with other factors, as predictors.
      Inattention, but not hyperactivity-impulsivity, significantly predicted
      adolescent tobacco use and young adult daily tobacco use. Peer substance use,
      parental substance use, and conduct disorder also predicted increases in tobacco
      use. African American ethnicity was strongly protective against later tobacco
      use.

PMID- 17516759
TI  - Movement abnormalities and the progression of prodromal symptomatology in
      adolescents at risk for psychotic disorders.
AB  - The link between movement abnormalities and psychotic disorders is presumed to
      reflect common neural mechanisms that influence both motor functions and
      vulnerability to psychosis. The prodromal period leading to psychotic disorders
      represents both a viable point for intervention and a developmental period that,
      if studied, could shed light on etiology; however, no published studies have
      examined the temporal progression of this link. A group with high levels of
      prodromal symptomatology (i.e., adolescents with schizotypal personality disorder
      [SPD]; n = 42) and both psychiatric controls (with other personality disorders or
      conduct disorder [OD]; n = 30) and nonpsychiatric controls ([NC]; n = 49) were
      recruited. Videotapes of structured psychiatric interviews were coded for
      movement abnormalities by raters blind to participants' diagnostic status, and
      follow-up assessments were conducted 1 year later. Controlling for psychotropic
      medications, the authors found that adolescents with SPD exhibited significantly
      more motor abnormalities in the face and upper body than did OD and NC controls.
      At baseline, movement abnormalities were positively correlated with the severity
      of positive, negative, and total prodromal symptoms. Within the SPD group,
      baseline movement abnormalities predicted symptom severity 1 year later. Movement
      abnormalities represent an early risk indicator that may be predictive of later
      symptom severity and potentially of psychosis onset.

PMID- 17516760
TI  - Patients with schizophrenia demonstrate dissociation between affective experience
      and motivated behavior.
AB  - Self-reported emotional experience does not differ between patients with
      schizophrenia and healthy individuals, suggesting that the anhedonia in
      schizophrenia instead reflects decoupling of affect from motivated behavior. In 2
      behavioral conditions, participants with schizophrenia and healthy participants
      were able to prolong or decrease exposure to stimuli while stimuli were present
      or alter the likelihood of future exposure to stimuli on the basis of internal
      representations. They also provided self-reports of affective experience.
      Patients showed weaker correspondence between behavior and ratings than did
      comparison participants. The effect was amplified when patients responded on the
      basis of internal rather than evoked stimulus representations. These data suggest
      that the motivational deficits in schizophrenia reflect problems in the ability
      to translate experience into action.

PMID- 17516761
TI  - Verbal communication impairments and cognitive control components in people with
      schizophrenia.
AB  - Schizophrenia involves multiple communication impairments, including (a)
      disorganized speech, or formal thought disorder (FTD); and (b) decreased speech
      output, or poverty of speech. Both FTD and poverty of speech have been
      hypothesized to be associated with deficits in executive functioning or cognitive
      control. The current study examined whether FTD and poverty of speech were
      differentially associated with two distinct aspects of cognitive control, working
      memory and controlled retrieval. Compared with control participants (n = 30),
      people with schizophrenia (n = 47) exhibited poorer performance on both working
      memory and controlled retrieval tasks. However, only FTD (and not poverty of
      speech) was associated with poor working memory. In contrast, only poverty of
      speech (and not FTD) had a significant zero-order association with poor
      controlled retrieval. At the same time, working memory and controlled retrieval
      interacted to predict FTD, with the highest amount of FTD associated with both
      poor working memory and poor controlled retrieval. In contrast, psychometric
      control tasks were not associated with FTD or poverty of speech. This research
      suggests that FTD and poverty of speech are differentially associated with
      deficits in distinct aspects of cognitive control.

PMID- 17516762
TI  - Cognitive processing of facial affect: connectionist model of deviations in
      schizophrenia.
AB  - Connectionist-model simulations of competing hypotheses of cognition in
      schizophrenia were constructed and tested. Emphasis was placed on judgment of
      affect, a prominent area of disturbance in this disorder with potential
      implications for social impairment. Participants with paranoid or nonparanoid
      schizophrenia and control participants provided judgments of affect as expressed
      in photographic faces. Schizophrenia groups were less accurate than control
      groups, and the paranoid group had greater latencies than did other groups. Model
      predictions simultaneously addressed judgment content and latencies for each
      trial. Results provide a connectionist extension of an account of deficits in
      schizophrenia that originated at the computational (stochastic modeling) level of
      analysis. This account postulates extra stages of item encoding but no reduction
      in formally defined processing capacity. It also provides for abnormalities in
      both judgment patterns and duration and is consistent with biological accounts of
      schizophrenia deficits. The substantive findings are supported by strategic
      innovations in the construction and testing of connectionist models.

PMID- 17516763
TI  - COMT val158Met and executive control: a test of the benefit of specific deficits
      to translational research.
AB  - The role of catechol-O-methyltransferase (COMT) val158met in prefrontal cortical
      deficits associated with the liability to schizophrenia remains controversial.
      This study evaluated 464 healthy adult participants using three measures of
      executive functions in working memory: a 3-back version of the N-back continuous
      performance task (CPT) and two variants of the AX-CPT. The interpretability of N
      back performance was confounded by possible generalized deficits, whereas the AX
      variants included internal controls for uncovering specific deficits. There was
      no relationship between the COMT genotype and N-back performance, whereas val/val
      individuals had a specific deficit on a dot-pattern version of the AX-CPT. In
      this case, a specific executive function known as context processing appeared to
      be compromised. These data suggest that the interpretability gained by including
      task manipulations to uncover specific deficits can enhance associations between
      cognitive and genetic levels of analysis.

PMID- 17516764
TI  - Temporal course and structural relationships among dimensions of temperament and
      DSM-IV anxiety and mood disorder constructs.
AB  - The temporal stability and directional relations among dimensions of temperament
      (e.g., neuroticism) and selected Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) disorder
      constructs (depression, generalized anxiety disorder, social phobia) were
      examined in 606 outpatients with anxiety and mood disorders, assessed on 3
      occasions over a 2-year period. Neuroticism/behavioral inhibition (N/BI) and
      behavioral activation/positive affect (BA/P) accounted for the cross-sectional
      covariance of the DSM-IV constructs. Although N/BI evidenced the most change of
      the constructs examined, initial levels of N/BI predicted less improvement in 2
      of the 3 disorder constructs. Unlike the DSM-IV disorder constructs, the temporal
      stability of N/BI increased as a function of initial severity. Moreover, N/BI
      explained all the temporal covariation of the DSM-IV disorder constructs. The
      results are discussed in regard to conceptual models of temperament that define
      N/BI and BA/P as higher order dimensions accounting for the course and
      covariation of emotional disorder psychopathology.

PMID- 17516765
TI  - Confirmatory factor analysis of the PTSD Checklist and the Clinician-Administered
      PTSD Scale in disaster workers exposed to the World Trade Center Ground Zero.
AB  - Although posttraumatic stress disorder (PTSD) factor analytic research has
      yielded little support for the DSM-IV 3-factor model of reexperiencing,
      avoidance, and hyperarousal symptoms, no clear consensus regarding alternative
      models has emerged. One possible explanation is differential instrumentation
      across studies. In the present study, the authors used confirmatory factor
      analysis to compare a self-report measure, the PTSD Checklist (PCL), and a
      structured clinical interview, the Clinician-Administered PTSD Scale (CAPS), in
      2,960 utility workers exposed to the World Trade Center Ground Zero site.
      Although two 4-factor models fit adequately for each measure, the latent
      structure of the PCL was slightly better represented by correlated
      reexperiencing, avoidance, dysphoria, and hyperarousal factors, whereas that of
      the CAPS was slightly better represented by correlated reexperiencing, avoidance,
      emotional numbing, and hyperarousal factors. After accounting for method
      variance, the model specifying dysphoria as a distinct factor achieved slightly
      better fit. Patterns of correlations with external variables provided additional
      support for the dysphoria model. Implications regarding the underlying structure
      of PTSD are discussed.

PMID- 17516766
TI  - Is there more to complicated grief than depression and posttraumatic stress
      disorder? A test of incremental validity.
AB  - There is growing interest in complicated grief reactions as a possible new
      diagnostic category for inclusion in the Diagnostic and Statistical Manual of
      Mental Disorders. However, no research has yet shown that complicated grief has
      incremental validity (i.e., predicts unique variance in functioning). The authors
      addressed this issue in 2 studies by comparing grief, depression, and
      posttraumatic stress disorder (PTSD) symptoms with different measures of
      functioning (interviewer ratings, friend ratings, self-report, and autonomic
      arousal). The 1st study (N = 73) used longitudinal data collected at 4 and 18
      months postloss, and the 2nd study (N = 447) used cross-sectional data collected
      2.5-3.5 years postloss. With depression and PTSD controlled, grief emerged as a
      unique predictor of functioning, both cross-sectionally and prospectively. The
      findings provide convergent support for the incremental validity of complicated
      grief as an independent marker of bereavement-related psychopathology.

PMID- 17516767
TI  - Associations between childhood trauma and emotion-modulated psychophysiological
      responses to startling sounds: a study of police cadets.
AB  - Childhood trauma may confer risk for adult psychopathology by altering emotional
      and physiological responses to subsequent stressors. Few studies have
      distinguished effects of childhood trauma from effects of current Axis I
      psychopathology on adult psychophysiological reactivity. The authors exposed 90
      psychiatrically healthy police cadets to startling sounds under increasing threat
      of shock while assessing their eyeblink electromyogram (EMG), skin conductance
      (SC), and heart rate responses. When compared with those who did not endorse
      early trauma (n = 65), cadets reporting childhood trauma (n = 25) reported less
      positive emotion and showed greater SC responses across all threat levels. They
      also showed threat-dependent elevations in reported negative emotions and EMG
      responses. Results suggest that childhood trauma may lead to long-lasting
      alterations in emotional and psychophysiological reactivity even in the absence
      of current Axis I psychopathology.

PMID- 17516768
TI  - Stress-response-dampening effects of alcohol: attention as a mediator and
      moderator.
AB  - The present study sought to characterize alcohol's stress-response-dampening
      (SRD) effects on multiple measures of stress and whether these effects are
      mediated by reductions in sustained attention and, further, whether baseline
      levels of sustained attention moderate SRD. One hundred six men consumed either
      an alcohol (0.70 g/kg) or a placebo beverage prior to learning that they would
      deliver a self-disclosing speech. Structural equation models controlling for
      multiple baseline periods indicated that alcohol directly reduced self-reported
      anxiety and skin conductance levels in response to the stressor. Alcohol's effect
      on reducing heart rate response, in contrast, was indirect and mediated by
      effects on prestress baseline. As hypothesized, differences in sustained
      attention partially mediated the effects of alcohol on skin conductance (but not
      heart rate or self-reported anxiety) and served as a moderator of alcohol's
      effects on skin conductance response. Findings are discussed in terms of
      theoretical links among alcohol consumption, specific cognitive abilities, and
      stress reactivity.

PMID- 17516769
TI  - Nonnormality and divergence in posttreatment alcohol use: reexamining the Project
      MATCH data "another way.".
AB  - Alcohol lapses are the modal outcome following treatment for alcohol use
      disorders, yet many alcohol researchers have encountered limited success in the
      prediction and prevention of relapse. One hypothesis is that lapses are
      unpredictable, but another possibility is the complexity of the relapse process
      is not captured by traditional statistical methods. Data from Project Matching
      Alcohol Treatments to Client Heterogeneity (Project MATCH), a multisite alcohol
      treatment study, were reanalyzed with 2 statistical methodologies: catastrophe
      and 2-part growth mixture modeling. Drawing on previous investigations of self
      efficacy as a dynamic predictor of relapse, the current study revisits the self
      efficacy matching hypothesis, which was not statistically supported in Project
      MATCH. Results from both the catastrophe and growth mixture analyses demonstrated
      a dynamic relationship between self-efficacy and drinking outcomes. The growth
      mixture analyses provided evidence in support of the original matching
      hypothesis: Individuals with lower self-efficacy who received cognitive behavior
      therapy drank far less frequently than did those with low self-efficacy who
      received motivational therapy. These results highlight the dynamical nature of
      the relapse process and the importance of the use of methodologies that
      accommodate this complexity when evaluating treatment outcomes.

PMID- 17516770
TI  - Two subtypes of psychopathic violent offenders that parallel primary and
      secondary variants.
AB  - Although psychopathy usually is treated as a unitary construct, a seminal theory
      posits that there are 2 variants: Primary psychopathy is underpinned by an
      inherited affective deficit, whereas secondary psychopathy reflects an acquired
      affective disturbance. The authors investigated whether psychopathy
      phenotypically may be disaggregated into such types in a sample of 367 prison
      inmates convicted of violent crimes. Model-based cluster analysis of the Revised
      Psychopathy Checklist (PCL-R; R. D. Hare, 2003) and trait anxiety scores in the
      psychopathic subgroup (n = 123; PCL-R > or = 29) revealed 2 clusters. Relative to
      primary psychopaths, secondary psychopaths had greater trait anxiety, fewer
      psychopathic traits, and comparable levels of antisocial behavior. Across
      validation variables, secondary psychopaths manifested more borderline
      personality features, poorer interpersonal functioning (e.g., irritability,
      withdrawal, poor assertiveness), and more symptoms of major mental disorder than
      primary psychopaths. When compared with the nonpsychopathic subgroup (n = 243),
      the 2 psychopathic variants manifested a theoretically coherent pattern of
      differences. Implications for etiological research and violence prevention are
      discussed.

PMID- 17516771
TI  - Stress exposure and affective modulation of aggressive behavior in men and women.
AB  - To study differences in the effects of stress exposure and affective responding
      on aggression in men and women, the authors examined the effects of an acute
      stressor (air blast) on subsequent aggressive behavior, measured as the intensity
      of shocks men and women delivered to a putative employee. The authors measured
      participants' affective responding using the startle reflex. Results showed that
      although men and women did not differ in their startle responses to the actual
      stressor, high stress led to contrasting patterns of subsequent aggressive
      behavior. Women under high stress responded with less aggression than women under
      low stress, whereas men exposed to high stress exhibited increases in aggression
      relative to those under low stress. Affective responding during the stressor
      differentially modulated aggression in men and women: Startle responses predicted
      increasing levels of aggression in men and less aggression in women. These
      findings suggest that although men and women show similar basic affective
      processing in response to stressors, the behavioral profiles associated with
      stress differ in men and women. These findings have implications for
      understanding gender differences in the prevalence of internalizing and
      externalizing psychopathology.

PMID- 17516772
TI  - A 20-year longitudinal study of body weight, dieting, and eating disorder
      symptoms.
AB  - The article describes a 20-year longitudinal study of body weight, dieting, and
      disordered eating in women and men. Body weight increased significantly over time
      in both women and men. However, women's weight perception and dieting frequency
      decreased over time, whereas men's weight perception and dieting frequency
      increased, and disordered eating declined more in women than in men from late
      adolescence to midlife. In both women and men, changes in weight perception and
      dieting frequency were associated with changes in disordered eating. In addition,
      adult roles such as marriage and parenthood were associated with significant
      decreases in disordered eating from late adolescence to midlife in women, whereas
      few associations were observed in men. Despite different developmental
      trajectories, women demonstrated more weight dissatisfaction, dieting, and
      disordered eating compared with men across the period of observation.

PMID- 17516773
TI  - Racial microaggressions in everyday life: implications for clinical practice.
AB  - Racial microaggressions are brief and commonplace daily verbal, behavioral, or
      environmental indignities, whether intentional or unintentional, that communicate
      hostile, derogatory, or negative racial slights and insults toward people of
      color. Perpetrators of microaggressions are often unaware that they engage in
      such communications when they interact with racial/ethnic minorities. A taxonomy
      of racial microaggressions in everyday life was created through a review of the
      social psychological literature on aversive racism, from formulations regarding
      the manifestation and impact of everyday racism, and from reading numerous
      personal narratives of counselors (both White and those of color) on their
      racial/cultural awakening. Microaggressions seem to appear in three forms:
      microassault, microinsult, and microinvalidation. Almost all interracial
      encounters are prone to microaggressions; this article uses the White counselor-
      client of color counseling dyad to illustrate how they impair the development of
      a therapeutic alliance. Suggestions regarding education and training and research
      in the helping professions are discussed.

PMID- 17516774
TI  - The Israeli-Palestinian peace process and its vicissitudes: insights from
      attitude theory.
AB  - The vicissitudes of the Israeli-Palestinian peace process since 1967 are analyzed
      using attitudes and related concepts where relevant. The 1967 war returned the
      two peoples' zero-sum conflict around national identity to its origin as a
      conflict within the land both peoples claim. Gradually, new attitudes evolved
      regarding the necessity and possibility of negotiations toward a two-state
      solution based on mutual recognition, which became the building stones of the
      1993 Oslo agreement. Lacking a commitment to a final outcome, the Oslo-based
      peace process was hampered by reserve options, which increased avoidance at the
      expense of approach tendencies as the parties moved toward a final agreement. The
      resulting breakdown of the process in 2000 produced clashing narratives,
      reflecting different anchors for judgment and classical mirror images. Public
      support for violence increased, even as public opinion continued to favor a
      negotiated two-state solution. Reviving the peace process requires mutual
      reassurance about the availability of a partner for negotiating a principled
      peace based on a historic compromise that meets the basic needs and validates the
      identities of both peoples.

PMID- 17516784
TI  - To ask, or not to ask, about abuse--New Zealand research.

PMID- 17516775
TI  - The psychology of ongoing threat: relative risk appraisal, the September 11
      attacks, and terrorism-related fears.
AB  - There are now replicated findings that posttraumatic stress disorder (PTSD)
      symptoms related to the September 11, 2001, attacks occurred in large numbers of
      persons who did not fit the traditional definition of exposure to a traumatic
      event. These data are not explained by traditional epidemiologic "bull's eye"
      disaster models, which assume the psychological effects are narrowly,
      geographically circumscribed, or by existing models of PTSD onset. In this
      article, the authors develop a researchable model to explain these and other
      terrorism-related phenomena by synthesizing research and concepts from the
      cognitive science, risk appraisal, traumatic stress, and anxiety disorders
      literatures. They propose the new term relative risk appraisal to capture the
      psychological function that is the missing link between the event and subjective
      response in these and other terrorism-related studies to date. Relative risk
      appraisal highlights the core notion from cognitive science that human perception
      is an active, multidimensional process, such that for unpredictable societal
      threats, proximity to the event is only one of several factors that influence
      behavioral responses. Addressing distortions in relative risk appraisal
      effectively could reduce individual and societal vulnerability to a wide range of
      adverse economic and ethnopolitical consequences to terrorist attacks. The
      authors present ways in which these concepts and related techniques can be
      helpful in treating persons with September 11- or terrorism-related distress or
      psychopathology.

PMID- 17516785
TI  - What are we teaching our students by not asking about abuse?

PMID- 17516786
TI  - It's ok to ask about past abuse.

PMID- 17516787
TI  - A public health perspective on "the ethics of asking and not asking about abuse".

PMID- 17516788
TI  - Asking research participants about trauma and abuse.

PMID- 17516791
TI  - Death feigning by grass snakes (Natrix natrix) in response to handling by human
      "predators.".
AB  - Death feigning, a variant of tonic immobility, is usually interpreted as a last
      resort antipredator measure. The authors describe death feigning in grass snakes
      (Natrix natrix) and test some of its potential correlates. Death feigning was
      seen in 66% of wild-caught snakes but was not seen in hatchlings from laboratory
      incubated eggs. Minimal indication of death feigning was mouth gaping, often with
      the tongue hanging free, but more dramatic cases involved voluntary supination
      and/or lack of muscle tone. Aside from hatchlings, which did not feign death,
      there was little variation in frequency or intensity of death feigning with body
      size. There was no effect of body temperature on death feigning nor were snakes
      that were moving when caught less likely to feign death than those that were not
      moving. Interpretation of the adaptive value of death feigning in grass snakes or
      in other animals is hampered by lack of evidence of this behavior in the field in
      response to natural predators.

PMID- 17516790
TI  - Constructing culture in cowbirds (Molothrus ater).
AB  - In past work, the authors produced divergent patterns of courtship and
      communication in juvenile male cowbirds (Molothrus ater) by providing them with
      different social experiences during their 1st year. Here the authors determined
      whether these different social patterns could be transmitted to new generations
      of juvenile males. In Experiment 1, the authors exposed groups of juveniles to
      adult males who differed in the amount of male-male competition they produced. In
      Experiment 2, they gave groups of juveniles either social access to adult males
      or only visual and acoustic access to those males. In both experiments, juvenile
      males developed patterns of courtship and competition similar to those expressed
      by the adult males with whom they had social contact. The juveniles never had the
      opportunity to observe some of the adults' behaviors that they came to replicate.
      This suggests that the role of the adults was to establish the social structure
      in the groups, modifying juveniles' early social interactions. Juveniles were
      then "cultured" within these different learning environments, constructing social
      behavior similar to the adult males' behavior in their 1st year.

PMID- 17516792
TI  - Rats (Rattus norvegicus) encode the shape of an array of discrete objects.
AB  - To navigate efficiently, a traveler must establish a heading using a frame of
      reference. A large body of evidence has indicated that humans and a variety of
      nonhuman animals utilize the geometry, or shape, of enclosed spaces as a frame of
      reference to determine their heading. An important and yet unresolved question is
      whether shape information from arrays of discrete objects and enclosed
      environments are represented, and utilized, in the same way. In the present
      study, rats were presented with a reference memory task in which they had to find
      water that was hidden in 1 of 4 discrete and unique objects placed at the
      vertices of a rectangle. The results indicate that rats could utilize both
      feature and geometry cues to locate the hidden goal. The rats' performance
      declined during transformation tests using a triangular array, indicating that
      the rats may have encoded the primary axis of the object array, rather than local
      cues, to direct their search.

PMID- 17516793
TI  - Chimpanzee (Pan troglodytes) anticipation of food return: coping with waiting
      time in an exchange task.
AB  - Despite controversial expectations that animals achieve reciprocal altruism, it
      is unclear if nonhuman species possess the necessary cognitive abilities. For
      reciprocal altruism, individuals must anticipate the loss of a commodity and
      accept a delay before some return. The authors investigated the abilities of 5
      chimpanzees (Pan troglodytes) to cope with increasing waiting duration in
      exchange tasks. Subjects had to keep a small cookie before returning it to a
      human partner to obtain a larger piece. For a piece 2, 4, or 8 times the size of
      the small piece, 3 of the 5 subjects waited for up to 4 min. For a piece 40 times
      larger, 4 of the 5 subjects waited up to 8 min. At long time lag, renouncement to
      wait occurred earlier than predicted by subjects' general waiting capacity,
      suggesting that the decision to wait was based on a trade-off between reward
      quantity and expected costs of the waiting duration. Chimpanzees could anticipate
      a delayed reward at a time scale of several minutes. If this reflects a cognitive
      limit in chimpanzees' anticipation capacity, reciprocal altruism by keeping track
      of costs and benefits over extended periods may be unlikely in chimpanzees.

PMID- 17516794
TI  - Is chimpanzee (Pan troglodytes) spatial attention reflexively triggered by gaze
      cue?
AB  - Humans show a reflexive shift in spatial attention triggered by gaze cues.
      Chimpanzees (Pan troglodytes) have an excellent ability to follow another's gaze,
      but they exhibit a limited capacity to engage in triadic interactions based on
      joint attention, suggesting the possibility of contributions of the different
      mechanisms underlying joint attention between humans and chimpanzees. The present
      study thus examined how the chimpanzee's visual spatial attention is triggered by
      gaze cues. Two chimpanzees showed no clear signs of attention shift triggered by
      various kinds of nonfacial and facial stimuli with averted gaze under the letter
      discrimination tasks but showed significant cueing effects when the head-turning
      cue was presented in a quasi-dynamic manner. These cueing effects were, however,
      affected by the predictability of the gaze cue: Highly predictive gaze cues
      caused stronger cueing effects than less predictive cues. Thus, these results
      suggest that the shift in spatial attention caused by gaze cues does occur in
      chimpanzees, but, in contrast to humans, vulnerability against the cue
      predictability suggests that the voluntary mechanism contributes more dominantly
      than the reflexive mechanism to this attention shift.

PMID- 17516795
TI  - Response of captive lowland gorillas (Gorilla gorilla gorilla) to different
      housing conditions: testing the aggression-density and coping models.
AB  - Several studies have suggested that primates react differently to spatial
      reduction. In this article, the authors tested some general hypotheses on primate
      response to spatial reduction by studying the Apenheul lowland gorillas (Gorilla
      gorilla gorilla; Apeldoorn, the Netherlands). The frequency of conflicts did not
      greatly change between the 2 housing settings, thus not supporting the density-
      aggression model. Indoor, gorillas performed touching behavior more often and
      increased their level of reconciliation. These findings support the coping model.
      Indoor, the gorillas also maintained broader interindividual distances by
      increasing the levels of sitting alone, avoidance, and dismissing behaviors. In
      conclusion, the Apenheul gorillas modified selectively the distribution of some
      patterns typical of their behavioral repertoire in response to a high-density
      condition. Both avoidance and coping tactics were used, thus revealing high
      levels of behavioral flexibility in this species.

PMID- 17516796
TI  - Grooming and coalitions in Japanese macaques (Macaca fuscata): partner choice and
      the time frame reciprocation.
AB  - Evidence of a reciprocal exchange of grooming and agonistic support in primates
      is mixed. In this study, the authors analyzed a large database of grooming and
      coalitions in captive female Japanese macaques (Macaca fuscata) to investigate
      their within-group distribution and temporal relations. Macaques groomed
      preferentially those individuals that groomed them most and supported
      preferentially those individuals that supported them most. They also supported
      preferentially those individuals that groomed them most and groomed
      preferentially those individuals that supported them most. These results were not
      explained by covariation of grooming and support with third variables such as
      kinship, rank, or time spent in proximity. However, receiving grooming did not
      increase the short-term probability of supporting a partner, and being supported
      did not increase the short-term probability of grooming a partner. The proximate
      mechanisms underlying the exchange of services were discussed in relation to the
      time frame of the behavioral choices made by the monkeys.

PMID- 17516797
TI  - Interference effects by spatial proximity and age-related declines in spatial
      memory by Japanese monkeys (Macaca fuscata): deficits in the combined use of
      multiple spatial cues.
AB  - Spatial information processing was assessed in 3 young (4-10 years old) and 4
      aged (24-25 years old) Japanese monkeys (Macaca fuscata) on 3 delayed nonmatching
      to-position (DNMP) tests with relatively short delays of 5 s. Each test had 3
      conditions of different horizontal distances between sample and to-be-nonmatched
      positions. Experiment 1 demonstrated that the performance on the DNMP test in
      both age groups was impaired when 2 stimulus positions were located next to each
      other; however, it was fairly accurate when they were located farther apart,
      suggesting that interference is introduced by spatial proximity. Experiment 2
      revealed age-related differences in the situation in which an additional spatial
      cue, depth information, was available by extending the stimulus array of the DNMP
      test to a 4 x 2 matrix. In this test, young monkeys performed accurately
      irrespective of position distance between stimuli, whereas the aged monkeys'
      performance remained the same as before. Experiment 3 confirmed that the
      recognition ability in aged monkeys was well preserved on DNMP tests with
      different objects. These patterns of results indicate that the ability to use
      information from multiple spatial cues is not accessible to the aged monkeys.

PMID- 17516798
TI  - Visual discrimination by heifers (Bos taurus) of their own species.
AB  - Species discrimination has been described in several taxa but rarely in domestic
      animals. In contrast to wild species, domestic species present a great phenotypic
      variety. This study investigated whether 10 Prim'Holstein heifers (Bos taurus)
      could discriminate images of cows from images of other domestic animals. The
      experiment was based on simultaneous discrimination. Responses were obtained
      through instrumental conditioning using a food reward. In Experiment 1, the
      reward was associated with a cow face and, in the reversal learning task, with
      faces of other domestic species. The results showed that in both tasks, cows were
      able to reach the criterion in few sessions. Therefore, despite great phenotypic
      variety (a cognitive challenge) cows were able to visually discriminate their own
      species from other domestic species.

PMID- 17516799
TI  - Postural effect on manual laterality in different tasks in captive grey-cheeked
      mangabey (Lophocebus albigena).
AB  - The authors examined the effects of task complexity and posture on laterality and
      compared lateralization during different tasks in 9 captive grey-cheeked
      mangabeys (Lophocebus albigena) during spontaneous food processing and 3
      experimental tasks. Comparisons with data of red-capped mangabeys (Cercocebus
      torquatus torquatus; semiterrestrial species) were used. Less than half the
      monkeys were lateralized for simple everyday activities, but 6 were lateralized
      for complex daily activities. Moreover, all the monkeys were lateralized when
      performing experimental tasks. Laterality at the group level was found for the
      bipedal task: Mangabeys were right-handed. Complexity of tasks increases
      laterality at the individual level. Significant differences between the 2 species
      of mangabeys were found, allowing us to confirm that postural constraints are a
      major factor in the emergence of group handedness.

PMID- 17516800
TI  - Absence makes the adaptations grow fonder: proportion of time apart from partner,
      male sexual psychology, and sperm competition in humans (Homo sapiens).
AB  - Sperm competition occurs when the sperm of multiple males concurrently occupy the
      reproductive tract of a female and compete to fertilize an egg. We used a
      questionnaire to investigate psychological responses to the risk of sperm
      competition for 237 men in committed, sexual relationships. As predicted, a man
      who spends a greater (relative to a man who spends a lesser) proportion of time
      apart from his partner since the couple's last copulation reported (a) greater
      sexual interest in his partner, (b) greater distress in response to his partner's
      sexual rejection, and (c) greater sexual persistence in response to his partner's
      sexual rejection. All effects were independent of total time since the couple's
      last copulation and the man's relationship satisfaction. Discussion addresses
      limitations of the current research and situates the current results within the
      broader comparative literature on adaptation to sperm competition.

PMID- 17516801
TI  - Eye-mouth-eye angle as a good indicator of face masculinization, asymmetry, and
      attractiveness (Homo sapiens).
AB  - Past research on male facial attractiveness has been limited by the reliance on
      facialmetric measures that are less than ideal. In particular, some of these
      measures are face size dependent and show only weak sexual dimorphism, which
      limits the ability to identify the relationship between masculinization and
      attractiveness. Here, the authors show that eye-mouth-eye (EME) angle is a
      quantitative and face size independent trait that is sexually dimorphic and a
      good indicator of masculinity and face symmetry. Using frontal photographs of
      female and male faces, the authors first confirmed that the EME angle (measured
      with the vertex in the middle of the mouth and the arms crossing the centers of
      pupils) was highly sexually dimorphic. Then, using pictures of young male faces
      whose attractiveness was assessed on a 7-point scale by young women, the authors
      showed that attractiveness rate was negatively correlated with EME angle and with
      the angle asymmetry. The results are compared with those that could be obtained
      with interpupilary or upper face height measurements. The authors discuss the
      relationship between attractiveness and both EME angle and its symmetry in the
      light of evolutionary psychology.

PMID- 17516802
TI  - The aftermath of 9/11: effect of intensity and recency of trauma on outcome.
AB  - Does trauma exposure have a long-term impact on the brain and behavior of healthy
      individuals? The authors used functional magnetic resonance imaging to assess the
      impact of proximity to the disaster of September 11, 2001, on amygdala function
      in 22 healthy adults. More than three years after the terrorist attacks,
      bilateral amygdala activity in response to viewing fearful faces compared to calm
      ones was higher in people who were within 1.5 miles of the World Trade Center on
      9/11, relative to those who were living more than 200 miles away (all were living
      in the New York metropolitan area at time of scan). This activity mediated the
      relationship between group status and current symptoms of posttraumatic stress
      disorder. In turn, the effect of group status on both amygdala activation
      (fearful vs. calm faces) and current symptoms was statistically explained by time
      since worst trauma in lifetime and intensity of worst trauma, as indicated by
      reported symptoms at time of the trauma. These data are consistent with a model
      of heightened amygdala reactivity following high-intensity trauma exposure, with
      relatively slow recovery.

PMID- 17516803
TI  - Accurate identification of fear facial expressions predicts prosocial behavior.
AB  - The fear facial expression is a distress cue that is associated with the
      provision of help and prosocial behavior. Prior psychiatric studies have found
      deficits in the recognition of this expression by individuals with antisocial
      tendencies. However, no prior study has shown accuracy for recognition of fear to
      predict actual prosocial or antisocial behavior in an experimental setting. In 3
      studies, the authors tested the prediction that individuals who recognize fear
      more accurately will behave more prosocially. In Study 1, participants who
      identified fear more accurately also donated more money and time to a victim in a
      classic altruism paradigm. In Studies 2 and 3, participants' ability to identify
      the fear expression predicted prosocial behavior in a novel task designed to
      control for confounding variables. In Study 3, accuracy for recognizing fear
      proved a better predictor of prosocial behavior than gender, mood, or scores on
      an empathy scale.

PMID- 17516804
TI  - Fear and anxiety as separable emotions: an investigation of the revised
      reinforcement sensitivity theory of personality.
AB  - The Gray and McNaughton (2000) theory draws on a wide range of animal data to
      hypothesize that the emotions of fear and anxiety are separable. The authors
      tested their hypothesis in two studies. The first study examined associations
      between scores on questionnaire measures of fear, anxiety, and neuroticism;
      correlational analysis revealed that fear and anxiety are not interchangeable
      constructs. The second study examined associations between scores on
      questionnaire measures of fear/anxiety and performance in a military training
      setting; regression analysis revealed that fear captured significant variance in
      performance that was not shared with anxiety. These results imply that hypotheses
      derived from nonhuman animal data may hold important implications for
      understanding human emotion and motivation, especially in relation to fear and
      anxiety.

PMID- 17516805
TI  - Individual differences in core affect variability and their relationship to
      personality and psychological adjustment.
AB  - How people's feelings change across time can be represented as trajectories in a
      core affect space defined by the dimensions of valence and activation. In this
      article, the authors analyzed individual differences in within-person affective
      variability defined as characteristics of core affect trajectories, introducing
      new ways to conceptualize affective variability. In 2 studies, participants
      provided multiple reports across time describing how they were feeling in terms
      of core affect. From these data, characteristics of participants' core affect
      trajectories were derived. Across both studies, core affect variability was
      negatively related to average valence, self-esteem, and agreeableness, and it was
      positively related to neuroticism and depression. Moreover, spin, a measure of
      how much people experienced qualitatively different feelings within the core
      affect space, was related more consistently to trait measures of adjustment and
      personality than other measures of within-person variability, including widely
      used measures of within-person single-dimension standard deviations.

PMID- 17516806
TI  - Emotional state and initiating cue alter central and peripheral motor processes.
AB  - Evidence indicates that voluntary and involuntary movements are altered by
      affective context as well as the characteristics of an initiating cue. The
      purpose of this study was to determine the contribution of central and peripheral
      mechanisms to this phenomenon. During the presentation of pleasant, unpleasant,
      neutral, and blank images, participants (N = 33) responded to auditory stimuli
      (startle, 107 dB startle or 80 dB tone) by initiating a bimanual isometric
      contraction of the wrist and finger extensor muscles. Analyses of
      electromyography and force measures supported the hypothesis that exposure to
      unpleasant images accelerates central processing times and increases the gradient
      of slope of peripheral movement execution. In addition, startle cues as compared
      with tone cues accelerated and magnified all temporal and amplitude indices.
      Collectively, these findings have noteworthy implications for (a) those seeking
      to facilitate the speed and force of voluntary movement (i.e., movement
      rehabilitation), (b) understanding the higher incidence of motor difficulty in
      individuals with affective disorders, and (c) those seeking to regulate emotional
      input so as to optimize the quality of intended movements.

PMID- 17516808
TI  - Attention for emotional faces under restricted awareness revisited: do emotional
      faces automatically attract attention?
AB  - Theoretical models of attention for affective information have assigned a special
      status to the cognitive processing of emotional facial expressions. One specific
      claim in this regard is that emotional faces automatically attract visual
      attention. In three experiments, the authors investigated attentional cueing by
      angry, happy, and neutral facial expressions that were presented under conditions
      of limited awareness. In these experiments, facial expressions were presented in
      a masked (14 ms or 34 ms, masked by a neutral face) and unmasked fashion (34 ms
      or 100 ms). Compared with trials containing neutral cues, delayed responding was
      found on trials with emotional cues in the unmasked, 100-ms condition, suggesting
      stronger allocation of cognitive resources to emotional faces. However, in both
      masked and unmasked conditions, the hypothesized cueing of visual attention to
      the location of emotional facial expression was not found. In contrary,
      attentional cueing by emotional faces was less strong compared with neutral faces
      in the unmasked, 100-ms condition. These data suggest that briefly presented
      emotional faces influence cognitive processing but do not automatically capture
      visual attention.

PMID- 17516809
TI  - Garner interference reveals dependencies between emotional expression and gaze in
      face perception.
AB  - The relationship between facial expression and gaze processing was investigated
      with the Garner selective attention paradigm. In Experiment 1, participants
      performed expression judgments without interference from gaze, but expression
      interfered with gaze judgments. Experiment 2 replicated these results across
      different emotions. In both experiments, expression judgments occurred faster
      than gaze judgments, suggesting that expression was processed before gaze could
      interfere. In Experiments 3 and 4, the difficulty of the emotion discrimination
      was increased in two different ways. In both cases, gaze interfered with emotion
      judgments and vice versa. Furthermore, increasing the difficulty of the emotion
      discrimination resulted in gaze and expression interactions. Results indicate
      that expression and gaze interactions are modulated by discriminability. Whereas
      expression generally interferes with gaze judgments, gaze direction modulates
      expression processing only when facial emotion is difficult to discriminate.

PMID- 17516810
TI  - Automatic attention does not equal automatic fear: preferential attention without
      implicit valence.
AB  - Theories of nonassociative fear acquisition hold that humans have an innate
      predisposition for some fears, such as fear of snakes and spiders. This
      predisposition may be mediated by an evolved fear module (Ohman & Mineka, 2001)
      that responds to basic perceptual features of threat stimuli by directing
      attention preferentially and generating an automatic fear response. Visual search
      and affective priming tasks were used to examine attentional processing and
      implicit evaluation of snake and spider pictures in participants with different
      explicit attitudes; controls (n = 25) and snake and spider experts (n = 23).
      Attentional processing and explicit evaluation were found to diverge; snakes and
      spiders were preferentially attended to by all participants; however, they were
      negative only for controls. Implicit evaluations of dangerous and nondangerous
      snakes and spiders, which have similar perceptual features, differed for expert
      participants, but not for controls. The authors suggest that although snakes and
      spiders are preferentially attended to, negative evaluations are not
      automatically elicited during this processing.

PMID- 17516811
TI  - Observational fear conditioning in the acquisition and extinction of attentional
      bias for threat: an experimental evaluation.
AB  - Anxious persons show automatic and strategic attentional biases for threatening
      information. Yet, the mechanisms and processes that underlie such biases remain
      unclear. The central aim of the present study was to elucidate the relation
      between observational threat learning and the acquisition and extinction of
      biased threat processing by integrating emotional Stroop color naming tasks
      within an observational differential fear conditioning procedure. Forty-three
      healthy female participants underwent several consecutive observational fear
      conditioning phases. During acquisition, participants watched a confederate
      displaying mock panic attacks (UCS) paired with a verbal stimulus (CS+), but not
      with a second nonreinforced verbal stimulus (CS-). As expected, participants
      showed greater magnitude electrodermal and verbal-evaluative (e.g., distress,
      fear) conditioned responses to the CS+ over the CS- word. Participants also
      demonstrated slower color-naming latencies to CS+ compared to the CS- word
      following acquisition and showed attenuation of this preferential processing bias
      for threat following extinction. Findings are discussed broadly in the context of
      the interplay between fear learning and processing biases for threat as observed
      in persons suffering from anxiety disorders.

PMID- 17516812
TI  - Anxiety and cognitive performance: attentional control theory.
AB  - Attentional control theory is an approach to anxiety and cognition representing a
      major development of Eysenck and Calvo's (1992) processing efficiency theory. It
      is assumed that anxiety impairs efficient functioning of the goal-directed
      attentional system and increases the extent to which processing is influenced by
      the stimulus-driven attentional system. In addition to decreasing attentional
      control, anxiety increases attention to threat-related stimuli. Adverse effects
      of anxiety on processing efficiency depend on two central executive functions
      involving attentional control: inhibition and shifting. However, anxiety may not
      impair performance effectiveness (quality of performance) when it leads to the
      use of compensatory strategies (e.g., enhanced effort; increased use of
      processing resources). Directions for future research are discussed.

PMID- 17516813
TI  - Dissociable effects of conscious emotion regulation strategies on explicit and
      implicit memory.
AB  - The authors manipulated emotion regulation strategies at encoding and
      administered explicit and implicit memory tests. In Experiment 1, participants
      used reappraisal to enhance and decrease the personal relevance of unpleasant and
      neutral pictures. In Experiment 2, decrease cues were replaced with suppress cues
      that directed participants to inhibit emotion-expressive behavior. Across
      experiments, using reappraisal to enhance the personal relevance of pictures
      improved free recall. By contrast, attempting to suppress emotional displays
      tended to impair recall, especially compared to the enhance condition. Using
      reappraisal to decrease the personal relevance of pictures had different effects
      depending on picture type. Paired with unpleasant pictures, the decrease cue
      tended to improve recall. Paired with neutral stimuli, the decrease cue tended to
      impair recall. Emotion regulation did not affect perceptual priming. Results
      highlight dissociable effects of emotion regulation on explicit and implicit
      memory, as well as dissociations between regulation strategies with respect to
      explicit memory.

PMID- 17516814
TI  - When "light" and "dark" thoughts become light and dark responses: affect biases
      brightness judgments.
AB  - Metaphors link positive affect to brightness and negative affect to darkness.
      Research has shown that such mappings are "alive" at encoding in that word
      meaning evaluations are faster when font color matches prevailing metaphors
      (positive = bright; negative = dark). These results, however, involved reaction
      times, and there are reasons to think that evaluations would be unlikely to
      influence perceptual judgments, the current focus. Studies 1-3 establish that
      perceptual judgments were biased in a brighter direction following positive (vs.
      negative) evaluations, and Study 4 shows that such biases are automatic. The
      results significantly extend the metaphor representation perspective. Not only do
      evaluations activate metaphors, but such metaphoric mappings are sufficient to
      lead individuals to violate input from visual perception when judging an object's
      brightness.

PMID- 17516815
TI  - Relationships between musical structure and psychophysiological measures of
      emotion.
AB  - Psychophysiological studies with music have not examined what exactly in the
      music might be responsible for the observed physiological phenomena. The authors
      explored the relationships between 11 structural features of 16 musical excerpts
      and both self-reports of felt pleasantness and arousal and different
      physiological measures (respiration, skin conductance, heart rate). Overall, the
      relationships between musical features and experienced emotions corresponded well
      with those known between musical structure and perceived emotions. This suggests
      that the internal structure of the music played a primary role in the induction
      of the emotions in comparison to extramusical factors. Mode, harmonic complexity,
      and rhythmic articulation best differentiated between negative and positive
      valence, whereas tempo, accentuation, and rhythmic articulation best
      discriminated high arousal from low arousal. Tempo, accentuation, and rhythmic
      articulation were the features that most strongly correlated with physiological
      measures. Music that induced faster breathing and higher minute ventilation, skin
      conductance, and heart rate was fast, accentuated, and staccato. This finding
      corroborates the contention that rhythmic aspects are the major determinants of
      physiological responses to music.

PMID- 17516816
TI  - Stability of laboratory-assessed temperamental emotionality traits from ages 3 to
      7.
AB  - A key component of temperament models is the presumed temporal stability of
      temperament traits. Although a substantial literature using parent report
      measures has addressed this claim, very few investigations have examined the
      stability of temperament using alternative measurement strategies, particularly
      those that involve direct assessment of emotional expressions. This study reports
      on the relative stability and heterotypic continuity of temperament traits
      measured via laboratory tasks and maternal report in a sample of children
      assessed at ages 3, 5, and 7, focusing on Positive Emotionality and Negative
      Emotionality. Relative stability of Positive Emotionality and Negative
      Emotionality traits ranged from moderate to high for laboratory and maternal
      report measures. Measures of emotional expressions exhibited levels of stability
      comparable to or higher than traits defined by other behavioral patterns (e.g.,
      sociability and engagement).

PMID- 17516817
TI  - Painful consequences of anger suppression.
AB  - The authors experimentally examined the effects of anger suppression on pain
      perception. On the basis of ironic process theory, they proposed that efforts to
      suppress experiential or expressive components of anger may paradoxically enhance
      cognitive accessibility of anger-related thoughts and feelings, thereby
      contaminating perception of succeeding pain in an anger-congruent manner.
      Participants were randomly assigned to nonsuppression or experiential or
      expressive suppression conditions during mental arithmetic with or without
      harassment. A cold-pressor task followed. Results revealed that participants
      instructed to suppress experiential or expressive components of emotion during
      harassment not only reported the greatest pain levels, but also rated the anger
      specific dimensions of pain uniquely strong. Results suggest that attempts to
      suppress anger may amplify pain sensitivity by ironically augmenting perception
      of the irritating and frustrating qualities of pain.

PMID- 17516818
TI  - Harnessing the need for immediate gratification: cognitive reconstrual modulates
      the reward value of temptations.
AB  - Many of us succumb to temptations, despite knowing that we will later regret
      doing so. How can such behavior be avoided? In three studies, the authors tested
      the hypothesis that reconstruing temptation as a test of a valued internal
      quality ("willpower") would decrease the tendency to succumb by reducing the
      appeal of the temptation. In Study 1, participants who construed a challenging
      handgrip task as a test of willpower resisted the temptation to terminate the
      painful task longer than participants who did not. In Study 2, participants
      performed a handgrip task twice. Only participants who changed their construal of
      the task into a test of willpower improved their performance. In Study 3,
      participants took a timed math test while being tempted by comedy clips.
      Participants who reconstrued the situation as willpower test compared with
      participants who did not, (a) enjoyed the videos less, and (b) were better able
      to resist the tempting videos. These studies demonstrate that cognitive
      reconstrual can be used to modify reward contingencies, so that succumbing to
      temptation becomes less appealing, and resisting temptation becomes more
      appealing.

PMID- 17516819
TI  - Sex differences in the time course of emotion.
AB  - Conventional wisdom holds that women are more "emotional" than men. However,
      research evidence suggests that sex differences in emotion are considerably more
      complex. The authors tested hypotheses about sex differences in the engagement of
      the approach and avoidance motivational systems thought to underpin emotional
      responses. The authors measured reported emotional experience and startle
      response magnitude both during the presentation and after the offset of emotional
      stimuli that engage these motivational systems to assess whether men and women
      differ in their patterns of immediate response to emotional stimuli and in their
      patterns of recovery from these responses. Our findings indicated that women were
      more experientially reactive to negative, but not positive, emotional pictures
      compared to men, and that women scored higher than men on measure of aversive
      motivational system sensitivity. Although both men and women exhibited
      potentiation of the startle response during the presentation of negative pictures
      relative to neutral pictures, only women continued to show this relative
      potentiation during the recovery period, indicating that women were continuing to
      engage the aversive motivational system after the offset of negative emotional
      pictures.

PMID- 17516820
TI  - Sources of accuracy in the empathic accuracy paradigm.
AB  - In the empathic accuracy paradigm, perceivers make inferences about the
      naturalistically occurring thoughts and feelings of stimulus persons, and these
      inferences are scored for accuracy against the stimulus persons' self-reported
      thoughts and feelings. The present study investigated sources of accuracy in this
      paradigm by presenting the stimulus tape in several cue modalities (full video,
      audio, transcript, or silent video) and with differing instructions (infer
      thoughts and feelings, infer thoughts, or infer feelings). Verbal information
      contributed the most to accuracy, followed by vocal nonverbal cues. Visual
      nonverbal cues contributed the least, though still at levels above zero. When
      asked to infer feelings, perceivers appeared to shift attention toward visual
      nonverbal cues and away from verbal cues, and the reverse occurred when they were
      asked to infer thoughts. The study contributes to understanding of factors
      contributing to accuracy in the empathic accuracy paradigm.

PMID- 17516821
TI  - More than mere mimicry? The influence of emotion on rapid facial reactions to
      faces.
AB  - Within a second of seeing an emotional facial expression, people typically match
      that expression. These rapid facial reactions (RFRs), often termed mimicry, are
      implicated in emotional contagion, social perception, and embodied affect, yet
      ambiguity remains regarding the mechanism(s) involved. Two studies evaluated
      whether RFRs to faces are solely nonaffective motor responses or whether
      emotional processes are involved. Brow (corrugator, related to anger) and
      forehead (frontalis, related to fear) activity were recorded using facial
      electromyography (EMG) while undergraduates in two conditions (fear induction vs.
      neutral) viewed fear, anger, and neutral facial expressions. As predicted, fear
      induction increased fear expressions to angry faces within 1000 ms of exposure,
      demonstrating an emotional component of RFRs. This did not merely reflect
      increased fear from the induction, because responses to neutral faces were
      unaffected. Considering RFRs to be merely nonaffective automatic reactions is
      inaccurate. RFRs are not purely motor mimicry; emotion influences early facial
      responses to faces. The relevance of these data to emotional contagion, autism,
      and the mirror system-based perspectives on imitation is discussed.

PMID- 17516822
TI  - Can the distress-signal and arousal-reduction views of crying be reconciled?
      Evidence from the cardiovascular system.
AB  - Theorists have staked out two ostensibly opposing views of human crying as either
      an arousing behavior that signals distress or a soothing behavior that reduces
      arousal after distress. The present study examined whether these views of crying
      might be reconciled by attending to physiological changes that unfold over crying
      episodes. Sixty female students watched neutral and cry-eliciting films while
      autonomic physiology, including respiratory sinus arrhythmia and pre-ejection
      period, was assessed. Crying participants exhibited heart rate increases that
      rapidly subsided after crying onset. Crying onset was also associated with
      increases in respiratory sinus arrhythmia and slowed breathing. All crying
      effects subsided by 4 minutes after onset. It is possible that crying is both an
      arousing distress signal and a means to restore psychological and physiological
      balance, depending on how and when this complex behavior is interrogated.

PMID- 17516823
TI  - [Liver biopsy and ultrasonography].

PMID- 17516824
TI  - [A prospective study about the usefulness of ultrasonographic monitoring after
      invasive liver procedures--liver biopsy and fine-needle aspiration (FNA)].
AB  - OBJECTIVE: To determine the need to perform ultrasound scans to all patients
      after liver biopsy or fine-needle aspiration (FNA) in order to detect
      complications with or without symptoms. MATERIAL AND METHODS: After liver biopsy
      or FNA using a regular protocol the patient is observed for 24 hours at the
      hospital, and all patients undergo an abdominal sonography at that time even in
      the absence of evident complications. RESULTS: 298 liver biopsies and 98 FNAs
      were performed. There were complications in 37 patients (9.34%): 36 (9.09%) were
      minor complications such as pain, vasovagal episodes, or small bleeding, and 1
      (0.25%) was a major complication with severe hemorrhage. Only 1 out of all 396
      procedures had a complication detected by ultrasounds (intrahepatic hematoma)
      while the patient was asymptomatic. CONCLUSIONS: The low incidence of
      complications occurring without symptoms, and their favorable course suggest that
      routine ultrasonography is not necessary after these techniques, and that it
      should be only performed when a complication is suspected.

PMID- 17516825
TI  - [Rectal cancer staging with endoscopic ultrasonography: correlation with
      pathological staging].
AB  - OBJECTIVE: our aim was to evaluate the accuracy of endosonography (EUS) in our
      experience, to stage rectal cancer. MATERIAL AND METHODS: we prospectively
      included all patients with rectal cancer staged in our unit from September 2002
      until February 2006 in a database. We selected those patients who had a complete
      EUS examination and were surgically treated without neoadjuvant therapy. Once we
      had the results of the histopathological staging (pTN), which was considered the
      gold standard, we compared the results of the previous EUS staging (uTN) with
      those of the pTN. We calculated the sensitivity, specificity, positive predictive
      value, negative predictive value and accuracy for each T stage, and for N staging
      considered as N positive or negative. We also calculated the global accuracy for
      T stage. We also calculated the agreement of uTN with pTN staging using the kappa
      index for N stage, and quadratic weighted kappa index for T stage. RESULTS: we
      staged 120 patients with rectal cancer during the mentioned period. Of these, 36
      patients met inclusion criteria and were evaluated, 21 women and 15 men. Mean age
      was 68,53+/-10,15 yo (range: 48-90). Global T stage accuracy was 83%. N stage
      accuracy was 72%. We obtained a S, E, PPV, NPV and A of 91, 100, 100, 96 and 97%
      for T1; 82, 88, 75, 91 and 86% for T2; 86, 91, 86, 91 and 89% for T3; and 14, 86,
      20, 80 and 72% for N stage respectively. Kappa value for T stage was 0,87
      indicating a "very good" agreement between uT and pT according to the kappa index
      criteria. Kappa value for N stage agreement was 0,005; "poor" according to the
      same criteria. CONCLUSIONS: in our experience, the diagnostic accuracy of EUS for
      T and N staging of rectal cancer is 83% and 72% respectively, similar results as
      previously published. uT staging for rectal cancer shows a "very good" agreement
      with pT staging.

PMID- 17516826
TI  - [Interventionist endoscopic ultrasonography. A retrospective analysis of 60
      procedures].
AB  - INTRODUCTION AND OBJECTIVE: interventionist endoscopic ultrasonography is
      increasingly used because of its growing indications. We present here our
      retrospective and initial experience (60 procedures) with endoscopic
      ultrasonography (EUS) both for diagnosis (EUS-FNA) and therapy (EUS-guided
      tumorectomy and mucosectomy). PATIENTS AND METHOD: in a group with 27 cases
      including 10 submucosal tumors (SMTs), 2 adenopathies, and 15 potential
      pancreatic tumors (8 pancreatic cancers), a sectorial EUS-FNA at 7.5 MHz was
      performed for diagnosis prior to therapy (mainly surgical). A pancreatic
      pseudocyst was drained. In 21 cases with 27 SMTs (10 patients with 13 carcinoids)
      a tumorectomy was carried out using the standard loop or assisted polypectomy
      technique with submucosal injection, and in a few cases (two) using elastic band
      ligation following a radial EUS at 7.5, 12, or 20 MHz. In 6 cases of superficial
      gastroesophageal cancer or gastric dysplasia an endoscopic mucosal resection
      (classic EMR) was performed after EUS or MPs at 7.5 and 20 MHz. Fifty-five
      patients with 60 lesions, 29 femaes and 26 males with a mean age of 60 years (30
      88 years) were retrospectively analyzed. RESULTS: diagnostic precision (P),
      sensitivity (S), specificity (Sp), positive predictive value (PPV), and negative
      predictive value (NPV) for EUS-FNA was 85, 83, 100, 100, and 43%, respectively,
      when comparing results with specimen histology. P was higher for adenopathies
      (100%) and pancreatic tumors (87%) than for SMTs (80%). No complications arose,
      except for one episode of upper gastrointestinal bleeding (UGIB) (3.7%) that was
      endoscopically and satisfactorily treated in a gastric SMT. In the group with 21
      patients (10 carcinoids with 13 tumors) 27 SMTs were endoscopically treated by
      tumorectomy with no perforation and only 2 UGIBs (7.4%), one of them self
      limited, recorded. Endoscopic resection was complete in 92% of cases. No
      complications occurred with classic EMR, and all patients are still alive with no
      evidence of relapse, either local or metastatic. In this group the rate of
      complete resections was 100%. CONCLUSIONS: EUS-FNA is a safe technique with high
      diagnostic accuracy. EUS-guided tumorectomy and mucosectomy are also safe and
      effective techniques in the endoscopic management of these tumors.

PMID- 17516827
TI  - Primary combined carcinoid and adenocarcinoma of the ileum associated with
      transitional carcinoma of the bladder. Single case report.
AB  - Composite neoplasms, carcinoid and adenocarcinoma have been reported to occur in
      several parts of the body, including the stomach, ampulla of Vater, large bowel,
      lung, and urinary bladder. Here we report a case of a 74-year-old male with a
      composite carcinoid-adenocarcinoma of the ileum associated with a transitional
      cell carcinoma of the bladder. The microscopical examination of the composite
      tumor showed an admixture of typical carcinoid tumor and moderately a
      differentiated adenocarcinoma. Immunohistochemically, the two components showed
      clear-cut differentiations. A review of the literature revealed that this is the
      first reported case of composite carcinoid-adenocarcinoma of the ileum associated
      with transitional cell carcinoma of the urinary bladder.

PMID- 17516828
TI  - [Increased prevalence of celiac disease in first and second-grade relatives. A
      report of a family with 19 studied members].
AB  - INTRODUCTION: celiac disease (CD) is an autoimmune condition that is triggered by
      the ingestion of gluten, a substance present in most cereals, and that affects
      genetically predisposed individuals. As a result, this condition is clearly
      familial, and mainly associated with HLA class II markers. OBJECTIVES: in this
      work we set out to analyze the prevalence of CD in an extensive family based on
      an index subject who had already died from this disease a few years ago, where CD
      had been complicated by the development of a small-bowel malignancy, namely an
      adenocarcinoma. METHODS: nineteen members were studied. They all were subjected
      to a diagnostic protocol including a detailed medical history, hemogram,
      coagulation tests, and blood biochemistry (including liver function tests, serum
      iron metabolism, circulating folic acid and vitamin B12 levels, thyroid function
      tests, tissue transglutaminase measurement, and genetic markers (DQ2 and DQ8).
      Suspect cases underwent gastroscopy plus multiple duodenal biopsy for
      confirmation. RESULTS: overall we encountered CD in 9/19 studied members, which
      represents 47.4% with the following distribution according to degree of kinship 
      four of seven siblings (57%); one of three children (33.3%); three of eight
      nephews and nieces (37.5%), and the only grandnephew, who was 9 years old.
      CONCLUSIONS: from all this it may be seen that family studies are needed every
      time a patient is diagnosed with celiac disease; these studies should include
      both first- and second-degree relatives, given the high prevalence encountered
      and the fact that these tests are relatively straighforward to perform.

PMID- 17516829
TI  - [Insulin-like growth factor I (IGF-I) and liver cirrhosis].
AB  - Insulin-like growth factor I (IGF-I) is a polypeptide hormone secreted by
      multiple tissues in response to growth hormone (GH). It is partly responsible for
      GH activity, and also has glucose-lowering and anabolizing effects. Ninety
      percent of circulating IGF-I originates in the liver and has autocrine,
      paracrine, and endocrine effects, the latter on multiple tissues. Liver cirrhosis
      results in a progressive decline of hepatic IGF-I output, and this factor may
      become undetectable in advanced disease. Some cirrhosis complications, mainly
      those nutritional and metabolic in nature (insuline resistance, malnutrition,
      osteopenia, hypogonadism, intestinal disorders), may be at least partly related
      to this IGF-I deficiency, since some IGF-I effects represent a reverse image of
      cirrhosis complications. Despite this, IGF-I replacement therapy has been never
      suggested for cirrhosis. A number of experimental studies in cirrhotic rats
      showed that therapy using low-dose recombinant IGF-I exerts two types of effect
      on experimental cirrhosis: a) liver improvement driven by improved hepatocellular
      function, portal hypertension, and liver fibrosis; and b) cirrhosis-related
      extrahepatic disorder improvement driven by improved food efficiency, muscle
      mass, bone mass, gonadal function and structure, and intestinal function and
      structure, with a normalization of sugar and amino acid malabsorption, and
      improved intstinal barrier function, manifested by reduced endotoxemia and
      bacterial translocation. Subsequently, the first randomized, double-blind,
      placebo-controlled, pilot clinical trial in a small number of cirrhotic patients
      showed increased serum albumin and improved energy metabolism as a result of IGF
      I use. Further clinical trials are needed to identify adequate IGF-I doses,
      administration duration and frequency, and the subgroup of cirrhotic patients who
      will benefit most from this replacement therapy.

PMID- 17516830
TI  - [Reye's syndrome in a pediatric patient].

PMID- 17516831
TI  - [The diagnosis of Peutz-Jeghers syndrome].

PMID- 17516832
TI  - [Pneumopericardium caused by gastropericardial fistula].
AB  - This is the case of a 56-year-old male who presented at our Emergency Room
      complaining of severe epigastric pain that radiated towards the left shoulder and
      neck. Pneumopericardium was diagnosed with plain chest X-rays, which indicated a
      gastropericardial fistula. A contrast X-ray film was taken using a water-soluble
      contrast. A full gastrectomy was performed with esophagojejunostomy
      reconstruction and pericardial drainage, which resulted in a favourable patient
      outcome.

PMID- 17516833
TI  - [Hepatotoxicity induced by amoxicillin].

PMID- 17516834
TI  - [Pneumomediastinum and cervical emphysema after "ecstasy" (3,4
      methylenedioxymetamphetamine) consumption].

PMID- 17516835
TI  - [Tracheoesophageal fistula in a politraumatized patient].

PMID- 17516836
TI  - [Unusual cause of late postoperative dysphagia after repair of hiatus hernia].

PMID- 17516837
TI  - [Primary aortoduodenal fistula].

PMID- 17516838
TI  - [Hepatotoxicity caused by a Noni (Morinda citrifolia) preparation].

PMID- 17516839
TI  - Seeking serenity: living with HIV/AIDS in rural Western Canada.
AB  - INTRODUCTION: The purpose of this naturalistic inquiry was to describe the
      experience of living with HIV infection in rural Alberta, Canada. Although the
      urban HIV epidemic has been well researched, the virus continues its spread into
      more remote populations where there is a need to understand and address its
      impact. Affected rural residents form a diverse and marginalized group that
      includes women, Aboriginal peoples, immigrants, injecting drug users, and men who
      have sex with men, yet there are few data available to inform appropriate health
      and social services and practice. A number of factors, such as stigma,
      invisibility, isolation, confidentiality, poverty, and risk behaviours,
      contribute to the rural experience, but have not been clearly explicated in the
      literature. This study was conducted in order to better understand the
      perceptions of health in a rural setting, the processes involved in accessing
      care, the challenges and benefits associated with rural life, and the
      relationship between personal beliefs and values and the nature of the disease.
      METHOD: Semi-structured interviews were conducted with six HIV-seropositive
      individuals and one caregiver who were living or had lived in rural settings, as
      well as four AIDS agency staff from a small city. Participants represented varied
      backgrounds, ages, sexual orientations, exposure to risk behaviours, lifestyles,
      roles, and citizenship. A naturalist inquiry approach was used in order to
      explore the qualitative aspects of the experience. Interviews were recorded,
      transcribed, and analyzed. Documents such as poetry, letters, field notes and
      journals served to enrich the data. RESULTS: Participants identified the
      components of health as a sense of wellbeing, quality of life, and independence.
      Within the context of HIV infection, health was achieved through three processes:
      (1) accommodating the reality of the diagnosis into daily life; (2) creating and
      engaging in supportive relationships and communities; and (3) reflecting on the
      meaning of one's life and future. Rural life had various meanings and
      implications for individuals, in terms of security, comfort, relationships,
      access to services, attitudes, dignity, and justice. Barriers and challenges to
      reaching health centred around a lack of skill and knowledge in human services
      workers, violation of confidentiality, difficulty associated with travel for
      medical care, and inadequate support for family caregivers. Participants
      suggested that the health of the community is reflected in the health of
      individuals. They expressed the hope that some day diversity would not only be
      tolerated, but would be celebrated by all members of society. CONCLUSIONS: Rural
      residents perceive and enact health in distinct ways. Caregivers must understand
      that health usually represents a concern only after it has failed and self
      initiated attempts to overcome problems have been unsuccessful. Participants in
      this study articulated their need to live in a society that acknowledges their
      diversity and honours their rights to access health and social supports in the
      community. Service providers may enhance care and promote health of this
      aggregate through education, attention to professional responsibilities,
      fostering resilient communities, and advocating for vulnerable members of
      society. Further research needs to be conducted in order to learn more about the
      relationships between HIV infection and rural living and the needs of people who
      live in such situations. With this knowledge, appropriate healthcare services can
      be developed and implemented to enhance the wellbeing and quality of life for
      individuals, families, and communities.

PMID- 17516840
TI  - Isletopathy in Type 2 diabetes mellitus: implications of islet RAS, islet
      fibrosis, islet amyloid, remodeling, and oxidative stress.
AB  - This review focuses primarily on islet structural and functional changes related
      to an activated islet renin- angiotensin system (RAS), islet oxidative-redox
      imbalance, the concurrence of islet fibrosis (pericapillary, intra- and peri
      islet), and islet amyloid deposition (pericapillary, intra- and peri-islet). The
      islet-acinar-portal vascular pathway and the emerging important anatomical and
      functional region, the islet-exocrine interface, are also discussed. Because
      there is an associated histopathological islet disease in type 2 diabetes
      mellitus (T2DM), the term isletopathy is discussed in detail. The isletopathy in
      T2DM is equally important as the other complications of diabetes. Special stains
      and special lighting (bright field and crossed polarized light) are utilized,
      along with light and transmission electron microscopy, in order to better
      understand islet structural remodeling in T2DM. The importance of an isletopathy
      in T2DM is supported by numerous remodeling changes within the islet and the
      islet-exocrine interface. While some of the structural findings are only
      preliminary observations, additional investigation in this area should lead to
      the development of new pathophysiological concepts and new therapies regarding
      the prevention and treatment of T2DM.

PMID- 17516841
TI  - Mid-region parathyroid hormone-related protein (PTHrP) and gene expression of MDA
      MB231 breast cancer cells.
AB  - We have previously shown that PTHrP(38-94) amide restrains growth and invasion in
      vitro, causes striking toxicity and accelerates death of some breast cancer cell
      lines, the most responsive being MDA-MB231, for which tumorigenesis was also
      attenuated in vivo. We have also demonstrated that mid-region PTHrP gains access
      to the nuclear compartment of these cells and displays DNA-binding properties in
      vitro by recognizing targets in both cellular chromatin and isolated
      oligonucleotides. Here, we examined whether PTHrP(38-94) amide was able to
      modulate gene expression of MDA-MB231 cells, employing a combination of
      conventional, differential display and semi-quantitative multiplex PCR
      techniques. The results obtained provide first evidence that PTHrP(38-94) amide
      can affect gene expression in tumor cells, identifying A4-differentiation
      protein/PLP2 as up-regulated, and HOX7/MSX1, COX6C, FZD6, OXR1 and TMCO4 as down
      regulated genes in treated cells, and suggest that the cytotoxic activity of the
      peptide can be ascribed, at least in part, to such transcriptional reprogramming.

PMID- 17516842
TI  - Characterization of peptidyl-tRNA hydrolase encoded by open reading frame Rv1014c
      of Mycobacterium tuberculosis H37Rv.
AB  - The enzyme peptidyl-tRNA hydrolase (Pth, EC 3.1.1.29) is essential for the
      viability of bacteria. The ORF Rv1014c of Mycobacterium tuberculosis H37Rv,
      designated as the mtpth gene, was cloned and over-expressed and the product was
      purified. Generation of polyclonal antibodies against the purified recombinant
      protein, termed MtPth, facilitated detection of endogenously expressed MtPth in
      M. tuberculosis H37Rv cell lysate. MtPth could release diacetyl-[(3)H]-lysine
      from diacetyl-[(3)H]-lysyl-tRNA(Lys) with Michaelis-Menten kinetic parameters of
      K (m)=0.7+/-0.2 microM and k (cat)=1.22+/-0.2 s(-1). Transformation of a
      pTrc99c/mtpth vector allowed the growth of E. coli thermosensitive Pth(ts) mutant
      strain AA7852 at the non-permissive temperature of 42 degrees C, demonstrating
      the in vivo activity of MtPth. In addition, at 39 degrees C, over-expression of
      MtPth in AA7852 cells allowed the cells to remain viable in the presence of up to
      200 microg/ml erythromycin. A 3D fold based on NMR and a structural model based
      on the E. coli Pth crystal structure were generated for MtPth. The essential
      nature of conserved active-site residues N12, H22 and D95 of MtPth for catalysis
      was demonstrated by mutagenesis and complementation in E. coli mutant strain
      AA7852. Thermal and urea/guanidinium chloride (GdmCl)-induced unfolding curves
      for MtPth indicate a simple two-state unfolding process without any
      intermediates.

PMID- 17516843
TI  - Calcium signalling in the regulation of PGC-1alpha, PDK4 and HKII mRNA
      expression.
AB  - The role of calcium signalling and specific intracellular calcium signalling
      pathways in regulating skeletal muscle tissue peroxisome proliferator-activated
      receptor gamma co-activator (PGC)-1alpha, hexokinase (HK)II and pyruvate
      dehydrogenase kinase (PDK)4 mRNA was examined. Cultured primary rat skeletal
      muscle cells were incubated for 6 h in caffeine or ionomycin. Because PGC-1alpha
      mRNA clearly showed greater induction with ionomycin, the latter was chosen for
      the main experiments, whereby cells were incubated for 6 h with either ionomycin
      alone or in combination with either cyclosporin A or KN-62. The PGC-1alpha mRNA
      level was increased (p<0.05) approximately six-fold and HKII mRNA content
      approximately two-fold by ionomycin relative to the corresponding controls,
      whereas the PDK4 mRNA content remained unaffected. Cyclosporin A abolished
      (p<0.05) and KN-62 reduced (p<0.1) the ionomycin-induced increase in PGC-1alpha
      mRNA. Electrical stimulation of in vitro incubated rat EDL muscle increased
      (p<0.05) PGC-1alpha mRNA by 2.2-fold after 4 h of recovery relative to a resting
      control, and this increase was absent when muscles were incubated with KN-62 or
      cyclosporin A. The present data strongly suggest that calcium signalling is
      involved in regulating the PGC-1alpha and HKII genes, but not PDK4. Both
      calcineurin and CaMK signalling seem to be involved in the calcium- and
      contraction-mediated PGC-1alpha up-regulation in skeletal muscle.

PMID- 17516844
TI  - Expression of the protein phosphatase 1 inhibitor KEPI is downregulated in breast
      cancer cell lines and tissues and involved in the regulation of the tumor
      suppressor EGR1 via the MEK-ERK pathway.
AB  - KEPI is a protein kinase C-potentiated inhibitory protein for type 1 Ser/Thr
      protein phosphatases. We found no or reduced expression of KEPI in breast cancer
      cell lines, breast tumors and metastases in comparison to normal breast cell
      lines and tissues, respectively. KEPI protein expression and ubiquitous
      localization was detected with a newly generated antibody. Ectopic KEPI
      expression in MCF7 breast cancer cells induced differential expression of 95
      genes, including the up-regulation of the tumor suppressors EGR1 (early growth
      response 1) and PTEN (phosphatase and tensin homolog), which is regulated by
      EGR1. We further show that the up-regulation of EGR1 in MCF7/KEPI cells is
      mediated by MEK-ERK signaling. The inhibition of this pathway by the MEK
      inhibitor UO126 led to a strong decrease in EGR1 expression in MCF7/KEPI cells.
      These results reveal a novel role for KEPI in the regulation of the tumor
      suppressor gene EGR1 via activation of the MEK-ERK MAPK pathway.

PMID- 17516845
TI  - Nitric oxide modulates expression of extracellular matrix genes linked to
      fibrosis in kidney mesangial cells.
AB  - Mesangial cells are thought to be important mediators of glomerular inflammation
      and fibrosis. Studies have established a direct role for nitric oxide (NO) in the
      regulation of gene expression in mesangial cells. Representational difference
      analysis was used to investigate changes in gene expression elicited by the
      treatment of S-nitroso-L-glutathione in rat mesangial cells. Seven upregulated
      and 11 downregulated genes were identified. Four out of 11 downregulated genes
      (connective tissue growth factor, thrombospondin-1, collagen type I alpha1 and
      collagen type I alpha2) are known to be linked to inflammation and fibrosis.
      Results were verified across species in mesangial cells treated with a series of
      NO donors using Northern blot analysis, quantitative real-time PCR and protein
      analysis methods. Induction of endogenous NO production by cytokine stimulation
      also triggered regulation of the genes. One example gene, connective tissue
      growth factor, was studied at the promoter level. Promoter-reporter gene studies
      in mesangial cells demonstrated that NO acts at the transcriptional level to
      suppress gene expression. Our results reveal a complex role of NO in regulating
      gene expression in mesangial cells and suggest an antifibrotic potential for NO.

PMID- 17516846
TI  - Discovery and characterization of human antibody inhibitors of pregnancy
      associated plasma protein-A.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease that cleaves
      insulin-like growth factor-binding proteins (IGFBPs) to release bioactive levels
      of free insulin-like growth factor. Specific and potent inhibitors of PAPP-A may
      further elucidate the biological functions of this protease and could prove to be
      of therapeutic value. Phage display was used to discover fully human antibody
      inhibitors of PAPP-A activity towards IGFBP4 cleavage. Estimates of the
      inhibition constants for these antibodies were subsequently determined using a
      novel continuous assay of PAPP-A protease activity that uses an internally
      quenched synthetic peptide substrate (DX-1655). DX-1655 was hydrolyzed by PAPP-A
      with a K(m) of 33 muM and a k(cat) of 0.3 s(-1) (k(cat)/K(m)=9.1x10(3) M(-1) s(
      1)). PAPP-A activity towards DX-1655 displays a bell-shaped pH profile, with
      pK(a) values of 8.2 and 10.8 and a maximum rate at approximately pH 9.5. Using
      this continuous assay, we measured apparent K(i) values of 1.7+/-0.2 and 7.4+/
      1.5 nM for the F2 and D9 antibodies, respectively.

PMID- 17516847
TI  - The protease domain of procollagen C-proteinase (BMP1) lacks substrate
      selectivity, which is conferred by non-proteolytic domains.
AB  - Procollagen C-proteinase (PCP) removes the C-terminal pro-peptides of
      procollagens and also processes other matrix proteins. The major splice form of
      the PCP is termed BMP1 (bone morphogenetic protein 1). Active BMP1 is composed of
      an astacin-like protease domain, three CUB (complement, sea urchin Uegf, BMP1)
      domains and one EGF-like domain. Here we compare the recombinant human full
      length BMP1 with its isolated proteolytic domain to further unravel the
      functional influence of the CUB and EGF domains. We show that the protease domain
      alone cleaves truncated procollagen VII within the short telopeptide region into
      fragments of similar size as the full-length enzyme does. However, unlike full
      length BMP1, the protease domain does not stop at this point, but degrades its
      substrate completely. Moreover, the protease domain cleaves other matrix proteins
      such as fibronectin, collagen I and collagen IV, which are left intact by the
      full-length enzyme. In addition, we show for the first time that thrombospondin-1
      is differently cleaved by both BMP1 and its catalytic domain. In summary, our
      data support the concept that the C-terminal domains of BMP1 are important for
      substrate recognition and for controlling and restricting its proteolytic
      activity via exosite binding.

PMID- 17516848
TI  - Two alpha subunits and one beta subunit of meprin zinc-endopeptidases are
      differentially expressed in the zebrafish Danio rerio.
AB  - Meprins are members of the astacin family of metalloproteases expressed in
      epithelial tissues, intestinal leukocytes and certain cancer cells. In mammals,
      there are two homologous subunits, which form complex glycosylated disulfide
      bonded homo- and heterooligomers. Both human meprin alpha and meprin beta cleave
      several basement membrane components, suggesting a role in epithelial
      differentiation and cell migration. There is also evidence that meprin beta is
      involved in immune defence owing to its capability of activating interleukin
      1beta and the diminished mobility of intestinal leukocytes in meprin beta
      knockout mice. Here we show for the first time by reverse transcription PCR,
      immunoblotting and immunofluorescence analyses that meprins are expressed not
      only in mammals, but also in the zebrafish Danio rerio. In contrast to the human,
      mouse and rat enzymes, zebrafish meprins are encoded by three genes,
      corresponding to two homologous alpha subunits and one beta subunit. Observations
      at both the mRNA and protein level indicate a broad distribution of meprins in
      zebrafish. However, there are strikingly different expression patterns of the
      three subunits, which is consistent with meprin expression in mammals. Hence, D.
      rerio appears to be a suitable model to gain insight into the basic physiological
      functions of meprin metalloproteases.

PMID- 17516849
TI  - Increase in kinins on post-exercise hypotension in normotensive and hypertensive
      volunteers.
AB  - Post-exercise hypotension is an important event for blood pressure regulation,
      especially in hypertensive individuals. Although post-exercise hypotension is a
      well-known phenomenon, the mechanism responsible is still unclear. The kallikrein
      kinin system is involved in blood pressure control, but its role in post-exercise
      hypotension has not yet been investigated. Thus, the purpose of this study was to
      investigate the involvement of the vasodilators bradykinin and des-Arg(9)-BK and
      kallikrein activity in post-exercise hypotension promoted by 35 min of cycle
      ergometer (CE) or circuit weight-training (CWT) bouts in normotensive and
      hypertensive individuals. A significant decrease in mean arterial pressure at 45
      and 60 min after CE and 45 min after CWT was observed in normotensive
      individuals. Hypertensive values of mean arterial pressure were significantly
      reduced at 45 and 60 min after CE and at 60 min after CWT. Before exercise,
      plasma bradykinin concentrations and kallikrein activity were higher in
      hypertensive compared to normotensive volunteers. Kinin levels increased in the
      groups evaluated at the end of the training period and 60 min post-exercise.
      These data suggest that the kallikrein-kinin system may be involved in post
      exercise hypotension in normotensive and hypertensive individuals subjected to CE
      and CWT bouts.

PMID- 17516850
TI  - Inhibition of cathepsin L-like proteases by cathepsin V propeptide.
AB  - The N-terminal propeptide domains of several cathepsin L-like cysteine proteases
      have been shown to possess potent inhibitory activity. Here we report the first
      kinetic characterisation of the inhibition properties of the cathepsin V
      propeptide (CatV PP). Using a facile recombinant approach we demonstrate
      expression, purification and evaluation of the CatV PP. This propeptide was found
      to behave as a tight-binding inhibitor against CatV (K (i) 10.2 nm). It also
      functions as an inhibitor against other members of the CatL-like subclass (CatL,
      9.8 nm; CatS, 10.7 nm; and CatK, 149 nm) and had no discernible effects upon the
      more distantly related CatB.

PMID- 17516851
TI  - Clinical chemistry reference database for Wistar rats and C57/BL6 mice.
AB  - Clinical chemistry data are decisive for evaluating altered organ function or
      damage in experimental animals. Few publications provide reliable clinical
      chemistry reference intervals, and analytical methods are often not described.
      Here, we investigated common clinical chemistry values in adult male and female
      Wistar rats and C57/BL6 mice (n=30/group). Blood samples were taken and analysed
      for electrolytes, substrates, metabolites and enzymes. In addition, we
      investigated cystatin C, an important marker of glomerular dysfunction. All data
      were obtained using commercially available kits frequently employed in most
      clinical chemistry laboratories and compared with data from other studies, as
      well as with human data. Significant gender-specific differences were observed in
      rats (electrolytes, retention parameters and transaminases) and in mice
      (cholesterol, glucose). High variability was noted for sodium, potassium,
      glucose, creatine kinase, lactate dehydrogenase and transaminase levels. Both
      rodent species showed markedly higher alpha-amylase activity than humans. This
      report demonstrates significant differences between genders for many analytes in
      rats and for fewer parameters in mice. Some reference values displayed major
      discrepancies between rodents and humans.

PMID- 17516852
TI  - Review: gene- and stem cell-based therapeutics for bone regeneration and repair.
AB  - Many clinical conditions require regeneration or implantation of bone. This is
      one focus shared by neurosurgery and orthopedics. Current therapeutic options
      (bone grafting and protein-based therapy) do not provide satisfying solutions to
      the problem of massive bone defects. In the past few years, gene- and stem cell
      based therapy has been extensively studied to achieve a viable alternative to
      current solutions offered by modern medicine for bone-loss repair. The use of
      adult stem cells for bone regeneration has gained much focus. This unique
      population of multipotential cells has been isolated from various sources,
      including bone marrow, adipose, and muscle tissues. Genetic engineering of adult
      stem cells with potent osteogenic genes has led to fracture repair and rapid bone
      formation in vivo. It is hypothesized that these genetically modified cells exert
      both an autocrine and a paracrine effects on host stem cells, leading to an
      enhanced osteogenic effect. The use of direct gene delivery has also shown much
      promise for in vivo bone repair. Several viral and nonviral methods have been
      used to achieve substantial bone tissue formation in various sites in animal
      models. To advance these platforms to the clinical setting, it will be mandatory
      to overcome specific hurdles, such as control over transgene expression, viral
      vector toxicity, and prolonged culture periods of therapeutic stem cells. This
      review covers a prospect of cell and gene therapy for bone repair as well as some
      very recent advancements in stem cell isolation, genetic engineering, and
      exogenous control of transgene expression.

PMID- 17516853
TI  - Highly poly(ethylene) glycolylated islets improve long-term islet allograft
      survival without immunosuppressive medication.
AB  - The surface modification of islets using poly(ethylene glycol) (PEG) is being
      studied as a means of preventing host immune responses against transplanted
      islets. In this study, to completely shield islets with PEG molecules, we
      increased the amount of PEG conjugated to islet surfaces, by multiple PEGylation
      or amplified PEGylation using poly-L-lysine, poly(allylamine), or
      poly(ethyleneimine), respectively. Amplified PEGylation was associated with islet
      cytotoxicity and functional impairment, but multiple PEGylation affected neither
      islet viability nor functionality. In addition, when triply PEGylated islets were
      allotransplanted into diabetic recipients, these islets survived in 3 of the 7
      recipients for more than 100 days without any immunosuppressive treatment.
      Moreover, the blood glucose levels of these 3 recipients were stable and in the
      normal range. Immunohistochemical analysis showed that 3 of 7 triply PEGylated
      islets transplants survived for 100 days and that 4 that were rejected before day
      20 were all immunologically protected from immune cells. However, unmodified
      islets were completely destroyed within 1 week. Consequently, we suggest that
      multiple PEGylation offers an effective means of reducing the immunogenicity of
      transplanted islets by increasing the amount of surface-bound PEG.

PMID- 17516854
TI  - Potential therapeutic clue of skin-derived progenitor cells following cytokine
      mediated signal overexpressed in injured spinal cord.
AB  - Recent evidence indicates that neural progenitor cell characters can be found in
      the population of adult skin-derived progenitor cells (SPCs). They have the
      ability to proliferate actively in vitro as spheres in suspension and they
      contain neural stem cells and several chemokines. Spheres derived from adult skin
      tissues have a higher capacity to differentiate into neurons in vitro. We report
      here that intravenous infusion of SPCs from adult skin ameliorated spinal cord
      lesions and improved motor function in laboratory mice with a spinal cord injury
      (SCI). After 4-5 weeks, transplanted SPCs survived and migrated into the injured
      region of the SCI very efficiently, and migrated cells were partially
      differentiated into neurons and glial cells. Behavioral and ultrastructural
      tissue analysis revealed that locomotor functions and remyelinated tissue lesions
      of SPCs engrafted onto SCI mice were restored significantly compared to those of
      the control group. Efficient migration of SPCs into SCI lesions suggests that SCI
      induced chemotaxic factors facilitate the migration of SPCs. Also, we verified
      that SCI-induced chemotaxic factors play an important role in proliferation,
      migration, and differentiation of engrafted SPCs. In transplantation paradigms,
      the interaction between the SCI microenvironment and engrafted cells will be very
      important in promoting host injury repair through the induction of cell
      migration, proliferation, and differentiation. Finally, adult SPCs can behave as
      a multipotent population, suggesting potential clinical applications for SCI
      therapy.

PMID- 17516855
TI  - The roles of hypoxia in the in vitro engineering of tissues.
AB  - Oxygen is a potent modulator of cell function and wound repair in vivo. The lack
      of oxygen (hypoxia) can create a potentially lethal environment and limit
      cellular respiration and growth or, alternatively, enhance the production of the
      specific extracellular matrix components and increase angiogenesis through the
      hypoxia-inducible factor-1 pathway. For the in vitro generation of clinically
      relevant tissue-engineered grafts, these divergent actions of hypoxia should be
      addressed. Diffusion through culture medium and tissue typically limits oxygen
      transport in vitro, leading to hypoxic regions and limiting the viable tissue
      thickness. Approaches to overcoming the transport limitations include culture
      with bioreactors, scaffolds with artificial microvasculature, oxygen carriers,
      and hyperbaric oxygen chambers. As an alternate approach, angiogenesis after
      implantation may be enhanced by incorporating endothelial cells, genetically
      modified cells, or specific factors (including vascular endothelial growth
      factor) into the scaffold or exposing the graft to a hypoxic environment just
      before implantation. Better understanding of the roles of hypoxia will help
      prevent common problems and exploit potential benefits of hypoxia in engineered
      tissues.

PMID- 17516856
TI  - Dermal fibroblasts genetically modified to express Runx2/Cbfa1 as a mineralizing
      cell source for bone tissue engineering.
AB  - Cell-based bone tissue engineering strategies have been effectively applied
      toward the development of grafting templates for skeletal repair and
      regeneration, but remain limited by inadequate availability of a robust
      mineralizing cell source. Dermal fibroblasts have emerged as a particularly
      promising cell alternative because they are harvested from autologous donors
      through minimally invasive skin biopsy and display a high capacity for in vitro
      expansion. In the present study, we investigated retroviral gene delivery of the
      osteogenic transcription factor Runx2 as a mineralization induction strategy in
      primary dermal fibroblasts. We demonstrate that constitutive overexpression of
      Runx2 induced osteogenic gene expression and mineralized nodule deposition in
      fibroblasts cultured on 3-dimensional fibrous collagen disks in vitro. Fourier
      transform infrared analysis revealed that Runx2 expressing fibroblasts deposit a
      carbonate-containing, poorly crystalline hydroxyapatite, whereas control
      constructs did not contain biologically-equivalent mineral. Importantly, Runx2
      transduced fibroblasts formed mineralized templates in vivo after implantation in
      a subcutaneous, heterotopic site, whereas minimal mineralization was evident in
      control constructs. Furthermore, immunohistochemical analysis indicated that
      Runx2-engineered cells co-localized with mineral deposits in vivo, suggesting
      that nodule formation primarily originated from transplanted donor cells. These
      results establish Runx2-genetic engineering as a strategy for the conversion of a
      non-osteogenic cellular phenotype into a mineralizing cell source for bone repair
      applications. Cellular therapies based on primary dermal fibroblasts would be
      particularly beneficial for patients with compromised ability to recruit
      endogenous osteoprogenitors to the site of injury as a result of extreme trauma,
      age, radiation treatment, or osteolytic disease.

PMID- 17516857
TI  - Review of the factors affecting bioavailability of soy isoflavones in humans.
AB  - Soy isoflavones have anticarcinogenic, antioxidant, and antiatherosclerotic
      activities. They also interact with the estrogen receptor, which makes them weak
      or moderate phytoestrogens. Because of their bioactivity, isoflavone
      bioavailability has been extensively studied in humans. This review summarizes
      data from intervention studies in humans, focusing on the factors that affect
      bioavailability. Summarizing data from 16 studies shows that the maximum
      concentration in plasma normalized to a constant dose of genistin is
      approximately 1.6 times that of genistein, and daidzin is approximately 1.8-fold
      higher than daidzein, whereas the half-life is not significantly different for
      aglycone and glucoside. There is a wide variation in the reported percentage
      urinary excretion that is not dependent on dose. Bioavailability is increased by
      a rapid gut transit time and by low fecal digestion rates and is decreased by a
      fiber-rich diet. There is no difference in bioavailability between pre- and
      postmenopausal women. The daily ingestion of soymilk for 1 wk does not affect
      bioavailability, but daily ingestion for a month increases excretion of equol in
      women. The factors or habitual diet characteristics that influence equol
      production are not clear, but equol production is limited with an immature flora.
      There is no consensus on which source of isoflavones results in the highest
      isoflavone bioavailability, and published studies present different results,
      although bioavailability is affected by whether the dose is given as food or
      drink. In conclusion, it is important to consider the factors affecting
      bioavailability of isoflavones when designing intervention studies.

PMID- 17516858
TI  - Increase in cruciferous vegetable intake in women previously treated for breast
      cancer participating in a dietary intervention trial.
AB  - Consumption of cruciferous vegetables has been associated with reduced breast
      cancer risk mechanistically and in population-based studies, although evidence
      has been inconsistent. This inconsistency may be related to limitations in
      quantifying and qualifying cruciferous vegetable exposure using standard
      instruments for dietary assessment (for example, food-frequency questionnaires,
      FFQs) or due to low levels of intake demonstrated among U.S. population samples.
      Cruciferous vegetable intake data are presented from a longitudinal study of a
      high-vegetable dietary intervention to reduce breast cancer recurrence among
      breast cancer survivors (n=1,156; 536 intervention and 620 comparison group
      subjects). Intake was assessed using repeat administration of an FFQ and cross
      sectional administration of a cruciferous vegetable-specific FFQ (CVFFQ). Mean
      intake in the intervention group assessed using the standard FFQ was 37.7 g/day
      at baseline and increased to 57.1 g/day at 12 mo (P=0.0001) and was sustained
      through 48 mo. Broccoli and cabbage were the most commonly consumed cruciferous
      vegetables, regardless of the instrument used to assess intake. Differences in
      intake by group assignment were shown for raw cruciferous vegetables (30.2 g/day
      vs. 24.6 g/day, assessed using the CVFFQ), suggesting increased exposure to
      biologically active, cancer-preventive food constituents. These data suggest that
      this study population will be the first U.S. population sample to provide ample
      quantity and variety in cruciferous intake to examine whether these vegetables
      are protective against breast cancer recurrence.

PMID- 17516859
TI  - Intake of fruits, vegetables, and soy foods in relation to breast cancer risk in
      Korean women: a case-control study.
AB  - We conducted a case-control study to examine the relationship between fruit,
      vegetable, and soy food intake and breast cancer risk in Korean women. Incident
      cases (n=359) were identified through cancer biopsies between March 1999 and
      August 2003 at two university hospitals in Seoul, Korea. Hospital-based controls
      (n=708) were selected from patients in the same hospitals during the same period.
      Subjects were asked by personal interview to indicate their average fruit,
      vegetable, and soy food intake for a 12-mo period 3 yr prior to the baseline
      phase. A food intake-frequency questionnaire (98 items) was given by a trained
      dietitian. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by
      unconditional logistic regression after adjustment for confounding factors and
      total energy intake. There was no association between the intake of total fruits,
      vegetables, or soy food and breast cancer risk. Increasing consumption of grapes
      was linked to a significant protective effect against risk of breast cancer
      (OR=0.66; 95% CI=0.41-0.86; P<0.01). Among the vegetables, reduced risk was
      observed with high tomato intake (OR=0.62; 95% CI=0.38-0.81; P<0.01). Among soy
      foods, high consumption of cooked soybeans, including yellow and black soybeans,
      had an association with reduced breast cancer (OR=0.67; 95% CI=0.45-0.91;
      P<0.02). Our data suggest that increased intake of some fruits, vegetables, and
      soy foods may be associated with breast cancer risk reduction in Korean women.

PMID- 17516860
TI  - Zapotin, a phytochemical present in a Mexican fruit, prevents colon
      carcinogenesis.
AB  - Zapotin (5,6,2',6'-tetramethoxyflavone), found in the tropical fruit zapote
      blanco (Casimiroa edulis), is consumed in many parts of the world, including
      Central America and Asia. Previously, we have demonstrated in vitro
      chemopreventive activity of extracts derived from the seeds of C. edulis. In the
      present study, we examined the effects of natural and synthetic zapotin in SW480,
      SW620, and HT-29 colon cancer cell lines and on the generation of aberrant crypt
      foci (ACF) using mice. Zapotin treatment (IC50=2.74x10(-7 M)) resulted in a
      marked suppression of cell proliferation in the HT-29 cells. Cell cycle analysis
      demonstrated a significant accumulation of cells in the G2-M phase, with a
      concomitant decrease of cells in the G0-G1 phase, after treatment with zapotin
      (molecular weight=342.35 g/mol; 1 microM for 18, 24, and 48 h). Zapotin treatment
      enhanced apoptosis in all of the colon cancer cell lines studied. For the study
      of ACF, 5-wk-old CF-1 mice were given subcutaneous injections of azoxymethane
      (AOM; 10 mg/kg body weight, BW) weekly for 2 wk, and zapotin (5 or 10 mg/kg BW;
      46 or 92 pmol/kg BW) or vehicle was administered intragastrically 7 days/wk. The
      mean number of ACF for the control group was 14.0+/-2.3, whereas the mean numbers
      of ACF in the zapotin-treated groups were 6.2+/-1.7 and 4.6+/-1.4 at doses of 5.0
      and 10.0 mg/kg BW, respectively. Loss of hexosaminidase, a lysosomal enzyme
      active in normal colonic crypts but decreased in up to 95% of ACF, was used as a
      second biomarker for colon carcinogenesis. Zapotin was found to significantly
      (P<0.01) prevent loss of hexosaminidase in the colon of AOM-treated mice. The
      present study is the first to report the potent anticancer activity of zapotin
      and suggests a role for zapotin both as a chemopreventive and a chemotherapeutic
      agent against colon cancer.

PMID- 17516861
TI  - Inhibition of gap junctional intercellular communication and activation of
      mitogen-activated protein kinase by tumor-promoting organic peroxides and
      protection by resveratrol.
AB  - Dicumyl peroxide (di-CuOOH) and benzoyl peroxide (BzOOH) act as tumor promoters
      in SENCAR mice, whereas di-tert-butylhydroperoxide does not. Tumor promotion
      requires the removal of growth suppression by inhibition of gap junctional
      intercellular communication (GJIC) and the induction of mitogenic intracellular
      pathways. We showed that di-CuOOH and BzOOH both reversibly inhibited GJIC and
      transiently activated mitogen-activated protein kinase, specifically, the
      extracellular receptor kinase at noncytotoxic conditions in WB-F344 rat liver
      epithelial cells, whereas the non-tumor-promoting di-tert-butylhydroperoxide did
      not inhibit GJIC or activate extracellular receptor kinase. di-CuOOH but not
      BzOOH inhibited GJIC through a phosphatidylcholine-specific phospholipase C
      dependent mechanism. N-acetylcysteine (NAC) was needed to prevent a cytotoxic,
      glutathione-depleting effect of BzOOH, whereas di-CuOOH was noncytotoxic and did
      not alter glutathione levels at all doses and times tested. Pretreatment of WB
      F344 cells with resveratrol, a polyphenolic antioxidant present in red wine,
      prevented at physiological doses the inhibition of GJIC by di-CuOOH but not from
      BzOOH and was effective in significantly preventing extracellular receptor kinase
      activation by both peroxides. NAC did not prevent any of the peroxide effects on
      either GJIC or extracellular receptor kinase, suggesting a specific antioxidant
      effect of resveratrol.

PMID- 17516862
TI  - Effects of flavonoids genistein and biochanin a on gene expression and their
      metabolism in human mammary cells.
AB  - Genistein (GEN) and biochanin A (BCA), dietary isoflavones, possess breast cancer
      preventive properties. Our objective was to examine the effect of physiologically
      relevant concentrations of BCA and GEN on gene expression in normal (HMEC),
      immortalized but nontumorigenic (MCF12A), and tumorigenic (MCF7) mammary cells
      and to determine whether the differences in gene expression are related to
      differences in metabolism in the three types of mammary cells. Using cDNA arrays,
      we compared the gene expression after a 48-h incubation with 1 microM BCA, GEN,
      or vehicle. Treatment with GEN or BCA produced the greatest number of significant
      changes in HMEC compared with MCF12A or MCF7 cells. Unlike GEN, effects of BCA on
      gene expression were mostly beneficial, involving induction of tumor suppressor
      genes. Different extents of metabolism were observed in the three mammary cell
      types; however, GEN concentrations were very low following either GEN or BCA
      administration in all of the three cell types. Because there were only very low
      concentrations of GEN, compared with BCA concentrations, in HMEC and MCF12A cells
      treated with BCA and different gene expression changes were found after BCA and
      GEN treatment, these findings suggest that BCA has distinct effects compared with
      GEN. The results suggest that BCA may represent a better breast cancer-preventive
      agent than GEN.

PMID- 17516863
TI  - Effect of fecal water on an in vitro model of colonic mucosal barrier function.
AB  - Fecal water (FW) has been shown to exert, in cultured cells, cytotoxic and
      genotoxic effects that have implications for colorectal cancer (CRC) risk. We
      have investigated a further biological activity of FW, namely, the ability to
      affect gap junctions in CACO2 cell monolayers as an index of mucosal barrier
      function, which is known to be disrupted in cancer. FW samples from healthy, free
      living, European subjects that were divided into two broad age groups, adult
      (40+/-9.7 yr; n=53) and elderly (76+/-7.5 yr; n=55) were tested for effects on
      gap junction using the transepithelial resistance (TER) assay. Overall, treatment
      of CACO2 cells with FW samples from adults increased TER (+4%), whereas FW from
      elderly subjects decreased TER (-5%); the difference between the two groups was
      significant (P<0.05). We also measured several components of FW potentially
      associated with modulation of TER, namely, short-chain fatty acid (SCFA) and
      ammonia. SCFAs (propionic, acetic, and n-butyric) were significantly lower in the
      elderly population (-30%, -35%, and -21%, respectively, all P A pound 0.01). We
      consider that FW modulation of in vitro epithelial barrier function is a
      potentially useful noninvasive biomarker, but it requires further validation to
      establish its relationship to CRC risk.

PMID- 17516864
TI  - Retinol inhibits the invasion of retinoic acid-resistant colon cancer cells in
      vitro and decreases matrix metalloproteinase mRNA, protein, and activity levels.
AB  - Retinol inhibits the growth of all-trans-retinoic acid (ATRA)-resistant human
      colon cancer cell lines through a retinoic acid receptor (RAR)-independent
      mechanism. The objectives of the current study were to determine if retinol
      inhibited the invasion of ATRA-resistant colon cancer cells independent of RAR
      and the effects of retinol on matrix metalloproteinases (MMPs). Retinol inhibited
      the migration and invasion of two ATRA-resistant colon cancer cell lines, HCT-116
      and SW620, in a dose-dependent manner. To determine if transcription,
      particularly RAR-mediated transcription, or translation of new genes was required
      for retinol to inhibit cell invasion, cells were treated with retinol and
      cycloheximide, actinomycin D, or an RAR pan-antagonist. Treatment of cells with
      retinol and cycloheximide, actinomycin D, or an RAR pan-antagonist did not block
      the ability of retinol to inhibit cell invasion. In addition, retinol decreased
      MMP-1 mRNA levels in both cell lines, MMP-2 mRNA levels in the SW620 cell line,
      and MMP-7 and -9 mRNA levels in the HCT-116 cell line. Retinol also decreased the
      activity of MMP-2 and -9 and MMP-9 protein levels while increasing tissue
      inhibitor of MMP-1 media levels. In conclusion, retinol reduces the metastatic
      potential of ATRA-resistant colon cancer cells via a novel RAR-independent
      mechanism that may involve decreased MMP mRNA levels and activity.

PMID- 17516865
TI  - Zyflamend, a polyherbal preparation, inhibits invasion, suppresses
      osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa
      B activation and NF-kappa B-regulated gene products.
AB  - Zyflamend, a polyherbal preparation, was designed based on constituents that
      exhibit antiproliferative, antiinflammatory, antioxidant, antiangiogenic, and
      apoptotic activities through a mechanism that is not well defined. Because the
      nuclear factor (NF)-kappaB has been shown to regulate proliferation, invasion,
      and metastasis of tumor cells, we postulated that Zyflamend modulates the
      activity of NF-kappa B. To test this hypothesis, we examined the effect of this
      preparation on NF-kappaB and NF-kappaB-regulated gene products. We found that
      Zyflamend inhibited receptor activator of NF-kappa B ligand-induced
      osteoclastogenesis, suppressed tumor necrosis factor (TNF)-induced invasion, and
      potentiated the cytotoxicity induced by TNF and chemotherapeutic agents, all of
      which are known to require NF-kappa B activation. Zyflamend suppressed NF-kappa B
      activation induced by both TNF and cigarette smoke condensate. The expression of
      NF-kappa B-regulated gene products involved in antiapoptosis (inhibitor-of
      apoptosis protein 1/2, Bcl-2, Bcl-xL, FADD-like interleukin-1betaconverting
      enzyme/caspase-8 inhibitory protein, TNF receptor-associated factor-1, and
      survivin) and angiogenesis (vascular endothelial growth factor, cyclooxygenase-2,
      intercellular adhesion molecule, and matrix metalloproteinase-9) was also down
      regulated by Zyflamend. This correlated with potentiation of cell death induced
      by TNF and chemotherapeutic agents. Overall, our results indicate that Zyflamend
      suppresses osteoclastogenesis, inhibits invasion, and potentiates cytotoxicity
      through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene
      products.

PMID- 17516866
TI  - Niacin deficiency alters p53 expression and impairs etoposide-induced cell cycle
      arrest and apoptosis in rat bone marrow cells.
AB  - One focus of chemoprevention research is the interaction of nutrients with
      specific molecular targets associated with the maintenance of genomic stability.
      This study tested the impact of dietary niacin status on bone marrow NAD+ and
      poly(ADP-ribose) (pADPr) levels, p53 expression, and etoposide (ETO)-induced
      apoptosis and cell cycle arrest. After 3 wk on niacin-deficient (ND), pair-fed
      niacin-replete (PF), or nicotinic acid-supplemented (4 g/kg diet) (NA) diets,
      Long-Evans rats were gavaged with ETO (25 mg/kg) or vehicle. ND and NA diets
      caused a 72% decrease and a 240% increase in bone marrow NAD+, respectively.
      Basal and ETO-induced pADPr levels differed dramatically among ND, PF, and NA
      diets (undetectable, 42 and 216 fmol/million cells, respectively; basal and
      undetectable, 119 and 484 fmol/million cells, respectively, following ETO). ND
      diet alone caused overexpression of two distinct isoforms of p53. Levels of p53
      in PF and NA marrow increased in response to ETO treatment, but this did not
      occur in ND bone marrow. Quantitative polymerase chain reaction of regular and
      alternative spliced variants of p53 mRNA revealed that niacin deficiency actually
      decreased both forms of p53 message, implicating protein stability in the
      accumulation of p53 in ND marrow. ETO-induced apoptosis (TUNEL) was suppressed
      during niacin deficiency and enhanced by supplementation. G1 arrest was also
      impaired in ND bone marrow relative to PF and NA. Despite a poor G1 arrest,
      p21waf1 was overexpressed in the ND bone marrow and dramatically induced
      following ETO treatment. In conclusion, dietary niacin deficiency causes changes
      in NAD+ and pADPr metabolism, alters p53 expression, and impairs cellular
      responses to DNA damage.

PMID- 17516867
TI  - Molecular mechanism of anti-prostate cancer activity of Scutellaria baicalensis
      extract.
AB  - Scutellaria baicalensis is a widely used Chinese herbal medicine historically
      used in antiinflammatory and anticancer therapy. The goals of the study were to
      1) determine its in vitro and in vivo anti-prostate cancer activity, 2)
      investigate its molecular mechanism directed at cell proliferation control
      including cyclooxygenase-2(COX-2) prostaglandin E2 (PGE2) and cyclins/cdks
      pathways, and 3) compare it with those of PC-SPES (PC stands for prostate cancer
      and spes is Latin for hope), a former herbal mixture for prostate cancer
      treatment of which S. baicalensis is a major constituent. Two human prostate
      cancer cell lines (LNCaP, androgen dependent, and PC-3, androgen independent)
      were assessed for growth inhibition. S. baicalensis exerted dose- and time
      dependent increased growth inhibition in both cell lines. However, the PC-3 cells
      IC50 (50% growth inhibition concentration) were slightly more sensitive than
      LNCaP cells (IC50=0.15 mg/ml), although the former is androgen independent. S.
      baicalensis was more effective in inhibition of cell growth compared with PC-SPES
      (IC50=0.38 mg/ml for PC-3 cells). Significant reduction of PGE2 synthesis in both
      cells after treatment with S. baicalensis resulted from direct inhibition of COX
      2 activity rather than COX-2 protein suppression. S. baicalensis also inhibited
      prostate-specific antigen production in LNCaP cells. Finally, S. baicalensis
      suppressed expression of cyclin D1 in LNCaP cells, resulting in a G1 phase
      arrest, while inhibiting cdk1 expression and kinase activity in PC-3 cells,
      ultimately leading to a G2/M cell cycle arrest. Animal studies showed a 50%
      reduction in tumor volume after a 7-wk treatment period. This study demonstrated
      that S. baicalensis may be a novel anticancer agent for the treatment of prostate
      cancer.

PMID- 17516868
TI  - Unique formosan mushroom Antrodia camphorata differentially inhibits androgen
      responsive LNCaP and -independent PC-3 prostate cancer cells.
AB  - Antrodia camphorata (AC), a precious and unique folkloric medicinal mushroom
      enriched in polyphenolics, isoflavonoids, triterpenoids, and polysaccharides, has
      been diversely used in Formosa (Taiwan) since the 18th century. In this study,
      prostate cancer (PCa) cell lines PC-3 (androgen independent) and LNCaP (androgen
      responsive) were treated with AC crude extract (ACCE) at 50-200 microg/mL,
      respectively, for 48 h. At the minimum effective dose 150 microg/mL, LNCaP showed
      a G1/S phase arrest with significant apoptosis. Such dose-dependent behavior of
      LNCaP cells in response to ACCE was confirmed to proceed as Akt-->p53-->p21-
      >CDK4/cyclin D1-->G1/S-phase arrest-->apoptosis, which involved inhibiting cyclin
      D1 activity and preventing pRb phosphorylation. In contrast, being without p53,
      PC-3 cells showed a G2/M-phase arrest mediated through pathway p21-->cyclin
      B1/Cdc2-->G2/M-phase arrest, however, with limited degree of apoptosis,
      implicating that ACCE is able to differentially inhibit the growth of different
      PCa cells by modulating different cell cycle signaling pathways. We conclude that
      this unique Formosan mushroom, A. camphorata, due to its nontoxicity, might be
      used as a good adjuvant anticancer therapy for prostate cancers despite its
      androgen-responsive behaviors, which has long been a serious drawback often
      encountered clinically in hormonal refractory cases treated by antihormonal
      therapies and chemotherapeutics.

PMID- 17516869
TI  - Managing multiple and extensively drug-resistant tuberculosis and HIV.
AB  - Global increases in multi-drug-resistant and extensively drug-resistant
      tuberculosis (TB), are threatening both TB and HIV treatment programs worldwide.
      Together, they raise concerns of a global epidemic of untreatable TB. In the
      developing world, the directly observed treatment, short course (DOTS) strategy
      is proving ineffective as available resources are being outstripped by the large
      number of patients needing treatment. Thus, TB treatment and outcomes are sub
      optimal, and multi-drug resistant and extensively drug-resistant TB are on the
      rise.

PMID- 17516870
TI  - Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and
      management.
AB  - Although effective anti-neoplastic agents, anthracyclines are limited by their
      well recognized and pervasive cardiotoxic effects. The incidence of late
      progressive cardiovascular disease in long-term survivors of cancer is
      established and may contribute to heart failure and death. To maximize the
      benefits of these drugs, a high-risk population has been identified and new
      strategies have been investigated to minimize toxic effects, including limiting
      the cumulative dose, controlling the rate of administration and using liposomal
      preparations and novel anthracycline analogues. Dexrazoxane also shows promise as
      a cardioprotectant during treatment. This paper reviews these strategies, as well
      as medications used to manage anthracycline-induced cardiotoxicity, and
      functional and biochemical means of monitoring cardiotoxicity, including
      echocardiography, radionuclide scans and biomarker analysis. The treatment of
      adult cancer survivors who have had anthracycline-related cardiotoxicity has not
      been systematically studied. Empirically, anthracycline-associated cardiac
      dysfunction is treated very similarly to other forms of heart failure. These
      treatments include avoiding additional cardiotoxic regimens, controlling
      hypertension, lifestyle changes, medications and heart transplantation.

PMID- 17516871
TI  - Botulinum neurotoxin type A in facial aesthetics.
AB  - Injection of botulinum neurotoxin type A has rapidly become the most common non
      surgical cosmetic procedure performed, due to its exceptional safety profile, as
      well as its ability to rejuvenate and enhance a number of facial areas. There are
      several marketed botulinum neurotoxin preparations, but products are not
      interchangeable as each possesses distinctive characteristics that are attributed
      to the unique toxin purification and manufacturing processes. These differences
      can emerge in the form of potency, duration of effect and the potential for
      migration outside targeted tissue, causing unwanted effects. However, although
      there are established preclinical pharmacologic and therapeutic differences
      between products, there are few well-controlled clinical comparisons in facial
      aesthetics. It is important for clinicians using these products to understand
      these differences as they relate to achieving desired outcomes for patients who
      seek improved facial aesthetics.

PMID- 17516872
TI  - Pharmacological options for advanced cancer patients with loss of appetite and
      weight.
AB  - The majority of patients with advanced cancer suffers from loss of appetite and
      loss of weight at some point during their disease course. This sign and this
      symptom herald an early demise. However, no therapeutic intervention, apart from
      effective antineoplastic therapy, has been able to reverse this syndrome totally,
      and, in turn, to reverse this prognostic effect. Most clinical trials have
      focused largely on palliating symptoms, and, to this end, progestational agents
      and corticosteroids have proven to be the most effective in terms of improving
      appetite. This article reviews data to support the use of these agents, discusses
      the findings of other more recent studies in this field and provides an overview
      of promising strategies that merit further investigation.

PMID- 17516873
TI  - Effective treatment strategies for paediatric community-acquired pneumonia.
AB  - Pneumonia is the leading cause of death in children under 5 years of age
      worldwide and a cause of morbidity in a considerable number of children. A number
      of studies have sought to identify the ideal choice of antibiotics, route of
      administration and optimum duration of treatment based on the most likely
      aetiological agents. Emerging bacterial resistance to antibiotics is also an
      important consideration in treatment. However, inconsistent clinical and
      radiological definitions of pneumonia make comparison between studies difficult.
      There is also a lack of well designed adequately powered randomised controlled
      trials. This review describes the difficulties encountered in diagnosing
      community-acquired pneumonia, aetiology, treatment strategies with
      recommendations and highlights areas for further research.

PMID- 17516874
TI  - Compared benefit of approved and experimental immunosuppressive therapeutic
      approaches in multiple sclerosis.
AB  - An important amount has been learnt about the mechanisms of action, efficacy and
      long-term toxicities of mitoxantrone. Importantly, recent observations strongly
      suggest that early administration of potent immunosuppressants (mitoxantrone and
      alemtuzumab) is definitely more effective than approved immunomodulators to delay
      or even reverse disability progression. Given the cardiotoxicity of mitoxantrone,
      restricting exposure to the drug to 2 or 3 years, the benefits and risks of
      immunosuppressants previously used as off-label treatments (cyclophosphamide and
      cladribine) have been revisited, and the potential efficacy in multiple sclerosis
      of recent immunosuppressants used in other autoimmune diseases, organ
      transplantation and cancer therapy has received increasing attention. Those
      immunosuppressants comprise monoclonal antibodies targeting B cells, lymphocytes
      and monocytes, IL-2 receptor and alpha4 integrin, as well as new molecules
      (pixantrone and isoxazole derivatives) and a new generation of immunosuppressants
      (fingolimod), which modulate lymphocyte re-circulation. This review addresses the
      most recent data concerning the efficacy and safety of mitoxantrone and of new
      experimental therapies that are presently in progress.

PMID- 17516875
TI  - Medical management of urinary stone disease.
AB  - Kidney stones occur in approximately 10% of patients in their lifetimes, and > 10
      crystal types have been reported in the literature. After treatment, a subset of
      these patients will have recurrent calculi, leading to significant morbidity and
      potential for serious chronic renal disease. Detailed metabolic evaluation is
      indicated in patients at high risk for stone recurrence, as a reversible
      metabolic abnormality can be identified in > 90% of them. Once the patient's
      underlying physicochemical and physiologic derangements are defined, targeted
      medical therapy can be initiated in order to prevent growth of pre-existing
      stones and new stone formation. In this report, the author provides a
      comprehensive review of the presently available selective and nonselective
      pharmacologic treatments for stones. Several exciting investigational
      pharmaceutical agents for kidney stone prevention are also discussed. Although
      many of these agents are effective, there remain clinical scenarios in which
      existing medicines are insufficient.

PMID- 17516876
TI  - Health economic review of recombinant activated factor VII for treatment of
      bleeding episodes in hemophilia patients with inhibitors.
AB  - Severe hemophilia with inhibitors is a rare disease with substantial clinical,
      humanistic and economic consequences. This review provides an overview of the
      role of recombinant activated factor VII (rFVIIa) versus plasma-derived bypassing
      agents for hemophilia with inhibitors and summarizes the 13 formal economic
      analyses (6 burden of illness and 7 comparative studies) that have been published
      in this indication. The findings suggest that the economic impact of rFVIIa has
      occurred primarily during hospitalization to manage major bleeding episodes and
      to allow for elective orthopedic surgeries that would not have been attempted
      prior to rFVIIa. Comparative analyses for on-demand treatment suggest that the
      total cost of treating a bleeding episode with rFVIIa may be lower than with
      plasma-based agents due to faster bleeding resolution, higher initial efficacy
      rates and avoidance of second and third lines of treatment.

PMID- 17516877
TI  - Efavirenz.
AB  - Treatment of HIV infection is typically carried out using a combination of at
      least three drugs. Efavirenz is a non-nucleoside reverse transcriptase inhibitor
      that acts by non-competitive inhibition of the viral enzyme. Efavirenz-based
      regimens have performed favorably compared with protease inhibitor-based
      therapies either in naive patients or as simplification strategies in pretreated
      subjects. Efavirenz is administered once-daily and its simple dosing schedule
      improves adherence to therapy allowing for durability of the virologic and
      clinical responses. In the case of viral rebound, K103N is the most commonly
      efavirenz-selected viral mutation. As non-nucleoside reverse transcriptase
      inhibitors have a distinctive adverse-event profile, protease inhibitor-sparing
      regimens may reduce the risk of metabolic complications, insulin resistance and
      peripheral fat redistribution.

PMID- 17516878
TI  - The role of eptifibatide in patients undergoing percutaneous coronary
      intervention.
AB  - Glycoprotein (GP) IIb/IIIa receptor antagonists inhibit the binding of ligands to
      activated platelet GP IIb/IIIa receptors and, therefore, prevent the formation of
      platelet thrombi. They have been extensively studied in patients undergoing
      percutaneous coronary intervention (PCI). Eptifibatide, one of the approved GP
      IIb/IIIa inhibitors, is a small heptapeptide that is highly selective and rapidly
      dissociates from its receptor after cessation of therapy. In clinical studies,
      concomitant administration of eptifibatide in patients undergoing elective PCI
      reduced thrombotic complications in the IMPACT-II (Integrilin to Minimize
      Platelet Aggregation and Prevent Coronary Thrombosis II) and ESPRIT (Enhanced
      Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy) trials. In
      the PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor
      Suppression Using Integrilin Therapy) trial, which included 10,948 patients with
      non-ST-elevation acute coronary syndromes, eptifibatide significantly reduced the
      primary end point of death and non-fatal myocardial infarction at 30 days
      compared with placebo. In patients with ST-segment elevation myocardial
      infarction (STEMI), eptifibatide has been studied as adjunct to primary PCI and
      improved epicardial flow and tissue reperfusion. Studies are now evaluating
      eptifibatide in high-risk patients with non-ST elevation acute coronary syndromes
      (NSTE-ACS) and a planned early invasive strategy in the EARLY-ACS (Eptifibatide
      Administration prior to Diagnostic Catherization and Revascularization to Limit
      Myocardial Necrosis in Acute Coronary Syndrome) trial and in patients with
      primary PCI for STEMI in comparison to abciximab in the EVA-AMI (Eptifibatide
      versus Abciximab in Primary PCI for Acute Myocardial Infarction) trial. After the
      completion of these trials, the value of etifibatide in patients undergoing PCI
      in different indications can be determined.

PMID- 17516879
TI  - The echinocandin micafungin: a review of the pharmacology, spectrum of activity,
      clinical efficacy and safety.
AB  - Micafungin is a relatively broad-spectrum antifungal agent available for clinical
      use in the US and Japan. By inhibiting the production of beta-1,3-glucan, an
      essential fungal cell wall component, micafungin has reduced toxicity to
      mammalian cells while maintaining potent antifungal activity against many
      pathogenic fungi including polyene- and azole-resistant isolates. Indeed,
      micafungin has been shown to be efficacious in the treatment of infections caused
      by Candida and Aspergillus species in clinical trials without the associated
      toxicities of amphotericin B formulations and drug interactions that occur with
      the azoles. In this review, the pharmacology, spectrum of activity, clinical
      efficacy and safety profile of micafungin are discussed.

PMID- 17516880
TI  - Posaconazole: a new broad-spectrum antifungal agent.
AB  - The rising incidence of invasive fungal infections and the emergence of broader
      fungal resistance have led to the need for novel antifungal agents. Posaconazole
      is a new member of the triazole class of antifungals. It is available as an oral
      suspension and has a favorable toxicity profile, has demonstrated clinical
      efficacy in the treatment of oropharyngeal candidiasis and has shown promise as
      salvage therapy for invasive aspergillosis, zygomycosis, cryptococcal meningitis
      and a variety of other fungal infections. In addition, data from randomized
      controlled studies support its efficacy for use in prophylaxis of invasive fungal
      infections in patients who are severely immunocompromised. The wide spectrum
      activity of posaconazole in in vitro studies, animal models and preliminary
      clinical studies suggest that posaconazole represents an important addition to
      the antifungal armamentarium.

PMID- 17516881
TI  - Recent advances in the medical management of breast cancer: highlights from the
      29th San Antonio Breast Cancer Conference San Antonio, TX, USA, 14-17 December
      2007.
AB  - The 29th edition of the San Antonio Breast Cancer Symposium was attended by a
      total of > 8000 basic scientists, translational researchers, clinical
      investigators and physicians gathering from approximately 80 countries worldwide.
      This is the largest meeting focusing on breast cancer, encompassing a wide array
      of topics from prevention, aetiology and diagnosis to molecular biology and
      treatment. From the main presentations at the meeting, it seems clear that
      combined efforts at prevention and treatment of this disease have translated into
      small, but significant, achievements. Much of the research in the area is focused
      on improving the therapeutic ratio of available treatments by better selection of
      patients.

PMID- 17516882
TI  - Religion, spirituality and medicine in Australia: research and clinical practice.

PMID- 17516883
TI  - Spirituality, religion and health: evidence and research directions.
AB  - Levels of spirituality and religious beliefs and behaviour are relatively high in
      Australia, although lower than those in the United States. There is mounting
      scientific evidence of a positive association between religious involvement and
      multiple indicators of health. The strongest evidence exists for the association
      between religious attendance and mortality, with higher levels of attendance
      predictive of a strong, consistent and often graded reduction in mortality risk.
      Negative effects of religion on health have also been documented for some aspects
      of religious beliefs and behaviour and under certain conditions. Health practices
      and social ties are important pathways by which religion can affect health. Other
      potential pathways include the provision of systems of meaning and feelings of
      strength to cope with stress and adversity.

PMID- 17516884
TI  - Prayer as medicine: how much have we learned?
AB  - Many people use prayer, and some studies have shown a positive association
      between prayer and improved health outcomes. This article explores four possible
      mechanisms by which prayer may lead to improved health. While acknowledging the
      efficacy of prayer and recognising the needs of patients, prayer, being a
      personal spiritual practice, cannot be prescribed, nor should it be used in place
      of medical care.

PMID- 17516885
TI  - Culture, spirituality, religion and health: looking at the big picture.
AB  - Religion provides things that are good for health and wellbeing, including social
      support, existential meaning, a sense of purpose, a coherent belief system and a
      clear moral code. But these benefits can also come from other sources.
      Conversely, religion is shaped by its social context in ways that affect its
      social role. Religion is no panacea when it comes to improving health. Religion's
      role in health needs to be examined in a broad context, especially the ways in
      which culture influences religion's expression of the spiritual.

PMID- 17516886
TI  - The importance of spirituality in medicine and its application to clinical
      practice.
AB  - Recent international and Australian surveys have shown that there is a need to
      incorporate the spiritual and religious dimension of patients into their
      management. By keeping patients' beliefs, spiritual/religious needs and supports
      separate from their care, we are potentially ignoring an important element that
      may be at the core of patients' coping and support systems and may be integral to
      their wellbeing and recovery. A consensus panel of the American College of
      Physicians has suggested four simple questions that physicians could ask patients
      when taking a spiritual history. Doctors and clinicians should not "prescribe"
      religious beliefs or activities or impose their religious or spiritual beliefs on
      patients. The task of in-depth religious counselling of patients is best done by
      trained clergy. In considering the spiritual dimension of the patient, the
      clinician is sending an important message that he or she is concerned with the
      whole person. This enhances the patient-physician relationship and is likely to
      increase the therapeutic impact of interventions. Doctors, health care
      professionals and mental health clinicians should be required to learn about the
      ways in which religion and culture can influence patients' needs and recovery.

PMID- 17516887
TI  - A review of spiritual assessment in health care practice.
AB  - The recent surge of interest in links between spirituality and health has
      generated many assessment approaches that seek to identify spiritual need and
      suggest strategic responses for health care practitioners. The interpretations of
      spirituality made within health frameworks do not do justice to the way
      spirituality is understood in society in general. Spiritual assessment should not
      impose a view or definition of spirituality, but should seek to elicit the
      thoughts, memories and experiences that give coherence to a person's life.
      Spiritual assessment tools should not be used without adequate exploration of the
      assumptions made. Assessment processes need to be adequately conceptualised and
      practically relevant.

PMID- 17516888
TI  - Ethical boundaries of spiritual care.
AB  - In an age that features technologically sophisticated medical interventions,
      patients still desire spiritually nurturing health care. Attention to patients'
      spiritual needs and resources in the clinical setting may raise a number of
      ethical questions. Five ethical guidelines are offered as illustrations of norms
      that respect patients' preferences and preserve health care professionals'
      integrity.

PMID- 17516889
TI  - Spirituality as sustenance for mental health and meaningful doing: a case
      illustration.
AB  - In the past 10-20 years there has been increasing interest in the relationship
      between spirituality and health. I interviewed six patients from community mental
      health centres, using a phenomenological approach to explore how concepts of
      spirituality, occupation and mental illness/mental health are related. One
      person's story is presented to illustrate the issues. Four main themes were
      identified: Spirituality is a phenomenon that provides meaning to life.
      Spirituality can help a person cope with mental illness. Spiritual beliefs can
      make everyday occupations more meaningful and health-enhancing. Some people find
      it valuable to engage in shared occupations that focus on spirituality.
      Spirituality is an important and relevant issue to be discussed between patients
      and health practitioners, provided that practitioners can exercise sensitivity,
      caution, tolerance and acceptance of values that may differ from their own.

PMID- 17516890
TI  - Developing healthy kids in healthy communities: eight evidence-based strategies
      for preventing high-risk behaviour.
AB  - Australian youth engage in behaviour that threatens their health and wellbeing.
      National surveys report that about a third of young Australians have tried an
      illicit drug. High rates of substance use and risky sexual behaviour among young
      Australians suggest that effective prevention efforts based on empirical evidence
      need to be expanded. Church-associated organisations are an untapped resource
      that could be used to improve the health and welfare of young people. We describe
      eight evidence-based elements to consider in designing strategies to prevent high
      risk behaviour in young people.

PMID- 17516891
TI  - Spiritual care and ageing in a secular society.
AB  - Providing spiritual care is about tapping into the concept of spirituality: core
      meaning, deepest life meaning, hope and connectedness. The search for meaning,
      connectedness and hope becomes more significant as older people are faced with
      the possibilities of frailty, disability and dementia. Spirituality, ageing and
      meaning in life can be discussed in the context of an alternative view of
      "successful ageing". A model of spiritual tasks in older age can help explain the
      spiritual dimension and provide a starting point for spiritual assessment.

PMID- 17516892
TI  - Rising to the health challenge for Aboriginal and Torres Strait Islander peoples:
      what will it take?
AB  - A united stand from medical professionals and organisations will send a powerful
      message.

PMID- 17516893
TI  - Diabetes in Indigenous Australians: possible ways forward.
AB  - Reducing the burden of diabetes will require action well beyond the health
      service sphere.

PMID- 17516894
TI  - Type 2 diabetes in Indigenous and non-Indigenous children and adolescents in New
      South Wales.
AB  - OBJECTIVE: To determine the incidence of type 2 diabetes mellitus (T2DM) in 2001
      2006 in young people < 19 years and the characteristics of T2DM in the Indigenous
      group. DESIGN AND SETTING: Prospective population-based incidence study, New
      South Wales. PARTICIPANTS: Primary ascertainment was from the Australasian
      Paediatric Endocrine Group NSW Diabetes Register, with secondary ascertainment
      from the National Diabetes Register (Australian Institute of Health and Welfare).
      MAIN OUTCOME MEASURES: Incidence of T2DM in young people in NSW; incidence of
      T1DM and T2DM in Indigenous young people; characteristics at diagnosis. RESULTS:
      There were 128 incident cases of T2DM (62 boys, 66 girls) in the study period.
      The median age at diagnosis was 14.5 years (interquartile range, 13.0-16.4), and
      90% were overweight or obese (body mass index > 85th percentile for age). Mean
      annual incidence was 2.5/100,000 person-years (95% CI, 2.1-3.0) in 10-18-year
      olds. Of the ethnic groups represented, white Australian comprised 29%,
      Indigenous 22%, Asian 22%, North African/Middle Eastern 12% and
      Maori/Polynesian/Melanesian 10%. The incidence of T2DM was significantly higher
      in the Indigenous than the non-Indigenous group (incidence rate ratio, 6.1; 95%
      CI, 3.9-9.7; P<0.001), but incidence rates of T1DM were similar (15.5 v
      21.4/100,000, respectively). CONCLUSIONS: T2DM accounts for 11% of incident cases
      of diabetes in 10-18-year-olds, and the majority are overweight or obese. The
      high rate among Indigenous Australian children supports screening for T2DM in
      this population.

PMID- 17516895
TI  - Point-of-care testing of capillary glucose in the exclusion and diagnosis of
      diabetes in remote Australia.
AB  - OBJECTIVES: To determine the utility of point-of-care (POC) capillary blood
      glucose measurements in the diagnosis and exclusion of diabetes in usual practice
      in primary health care in remote areas. DESIGN: Cross-sectional study comparing
      POC capillary glucose results with corresponding venous glucose levels measured
      in a reference laboratory. PARTICIPANTS: 200 participants aged 16-65 years
      enrolled: 198 had POC capillary glucose measurements; 164 also had acceptable
      venous glucose laboratory results. SETTING: Seven health care sites in the
      Kimberley region of Western Australia from May to November 2006. MAIN OUTCOME
      MEASURES: Concordance and mean differences between POC capillary blood glucose
      measurement and laboratory measurement of venous blood glucose level; POC
      capillary blood glucose equivalence values for excluding and diagnosing diabetes,
      and their sensitivity, specificity and positive-predictive value. RESULTS: The
      concordance between POC and laboratory results was high (rho=0.93, P<0.001). The
      mean difference in results was 0.48 mmol/L (95% CI, 0.23-0.73; limits of
      agreement, - 2.6 to 3.6 mmol/L). The POC capillary glucose equivalence values for
      excluding and diagnosing diabetes were < 5.5 mmol/L (sensitivity, 53.3%;
      specificity, 94.4%; positive-predictive value, 88.9%; for a venous value of < 5.5
      mmol/L) and >or= 12.2 mmol/L (sensitivity, 83.3%; specificity, 99.3%; positive
      predictive value, 95.2%; for a venous value of >or= 11.1 mmol/L), respectively.
      While the choice of glucometer and whether or not patients were fasting altered
      these results, they did not have a significant influence on the diagnostic
      utility of POC glucose measurement in this setting. CONCLUSION: POC capillary
      blood glucose analysers can be used as part of the process of diagnosing and
      excluding diabetes in remote rural communities using these locally established
      capillary equivalence values.

PMID- 17516896
TI  - Diabetes in the Torres Strait Islands of Australia: better clinical systems but
      significant increase in weight and other risk conditions among adults, 1999-2005.
AB  - OBJECTIVES: To (i) assess changes in clinical indicators of adults diagnosed with
      diabetes and (ii) estimate changes in risk factors and incidence of diabetes
      among adults without diabetes living in the Torres Strait and Northern Peninsula
      Area Health Service District in Queensland from 1999 to 2005. DESIGN AND
      PARTICIPANTS: (i) Annual audit of clinical records of Torres Strait Islander
      adults on diabetes registers in 21 primary care clinics, and (ii) a 5-year follow
      up of a community cohort of 207 Torres Strait Islander adults without diabetes
      who participated in the Well Person's Health Check in 2000-01 and 2005-06. MAIN
      OUTCOME MEASURES: Weight, height, waist circumference, fasting blood sugar (those
      without diabetes) and glycated haemoglobin (HbA1c; those with diabetes) levels,
      blood pressure (BP), fasting triglyceride and high-density lipoprotein
      cholesterol levels, urinary albumin-to-creatinine ratio and smoking status.
      RESULTS: The number of adults included on the diabetes register increased from
      555 in 1999 to 1024 in 2005. The mean age of patients diagnosed with diabetes
      decreased from 53.3 to 51.5 years, and their mean weight increased from 86.8 kg
      to 95.6 kg. Mean HbA1c level remained unchanged at about 9%, but the proportion
      with HbA1c level < 7% increased from 18.4% to 26.1%, and the proportion
      prescribed insulin increased from 14% in 2002 to 22% in 2005. The proportion with
      BP < 140/90 mmHg increased from 40.3% in 1999 to 66.8% in 2005. In the sample of
      207 adults without diabetes, from 2000 to 2006, there was a weight gain of about
      1 kg per person per year, and an annual increase in waist circumference of 0.8 cm
      in men and 1.2 cm in women. Crude incidence of diabetes was 29 (95% CI, 19-41)
      per 1000 person-years. There was a significant increase in diastolic blood
      pressure and fasting blood sugar levels, and no change in smoking habits.
      CONCLUSIONS: Clinical care of adults with diabetes has improved and more people
      with diabetes are being diagnosed. However, weight gain and high rates of
      glycaemia remain a challenge and will result in a large burden of complications,
      including renal failure. Incidence data from this sample extrapolate to 120 (95%
      CI, 103-147) new cases of diabetes in the District each year. Urgent action to
      improve nutrition, decrease smoking and increase physical activity is required to
      improve metabolic fitness in younger people.

PMID- 17516897
TI  - The urban-remote divide for Indigenous perinatal outcomes.
AB  - OBJECTIVE: To determine whether remoteness category of residence of Indigenous
      women affects the perinatal outcomes of their newborn infants. DESIGN AND
      PARTICIPANTS: A population-based study of 35 240 mothers identified as Indigenous
      and their 35 658 babies included in the National Perinatal Data Collection in
      2001-2004. MAIN OUTCOME MEASURES: Australian Standard Geographical Classification
      remoteness category, birthweight, Apgar score at 5 minutes, stillbirth,
      gestational age and a constructed measure of perinatal outcomes of babies called
      "healthy baby" (live birth, singleton, 37-41 completed weeks' gestation, 2500
      4499 g birthweight, and an Apgar score at 5 minutes >or= 7). RESULTS: The
      proportion of healthy babies in remote, regional and city areas was 74.9%, 77.7%
      and 77.6%, respectively. After adjusting for age, parity, smoking and diabetes or
      hypertension, babies born to mothers in remote areas were less likely to satisfy
      the study criteria of being a healthy baby (adjusted odds ratio [AOR], 0.87; 95%
      CI, 0.81-0.93) compared with those born in cities. Babies born to mothers living
      in remote areas had higher odds of being of low birthweight (AOR, 1.09; 95% CI,
      1.01-1.19) and being born with an Apgar score < 7 at 5 minutes (AOR, 1.63; 95%
      CI, 1.39-1.92). CONCLUSIONS: Only three in four babies born to Indigenous mothers
      fell into the "healthy baby" category, and those born in more remote areas were
      particularly disadvantaged. These findings demonstrate the continuing need for
      urgent and concerted action to address the persistent perinatal inequity in the
      Indigenous population.

PMID- 17516898
TI  - Attitudes and behaviours of young Indigenous people in Townsville concerning
      relationships, sex and contraception: the "U Mob Yarn Up" project.
AB  - OBJECTIVE: To gain some understanding of the attitudes and behaviours of
      Indigenous young people in Townsville concerning relationships, contraception and
      safe sex. DESIGN: Cross-sectional study using a computer-assisted self
      administered survey and single-sex focus group discussions designed by a Young
      Mums' Group operating on participatory action principles and acting as peer
      interviewers. PARTICIPANTS AND SETTING: 171 Indigenous students in Years 9-11 at
      three high schools and 15 residents of a homeless youth shelter in Townsville,
      Queensland, 27 April - 8 December 2004. MAIN OUTCOME MEASURES: Self-reported
      attitudes and behaviour about relationships, sexual intercourse and
      contraception. RESULTS: 84/183 participants (45.9%) reported past sexual
      intercourse, with 56.1% commencing intercourse at age 13-14 years. The likelihood
      of having had sex increased with being male (P=0.001), increasing age, increased
      perceived sexual activity of peer group (both P=0.000), and drinking alcohol at
      least weekly (P=0.015). Young women were more likely to report unwanted sexual
      touching (P=0.031), and less likely to report enjoying sexual intercourse
      (P=0.001). The main qualitative themes concerned females' reputations, coercion,
      and denial of female desire. Only 49/80 participants (61.3%) reported always
      using condoms. The main reasons for not using contraception were "just not
      thinking about it", shame, and problems with access. Despite having reasonable
      knowledge about contraception, most lacked the confidence and negotiation skills
      to communicate with partners about condom use. CONCLUSIONS: Like teenagers
      elsewhere, Indigenous teenagers in Townsville are becoming sexually active at a
      young age, and not practising safe sex reliably. The need to protect their
      reputations puts young women at risk by not being prepared for safe sex by
      carrying condoms.

PMID- 17516899
TI  - Health of Aboriginal and Torres Strait Islander children in remote Far North
      Queensland: findings of the Paediatric Outreach Service.
AB  - AIM: To describe the pattern of disease and other health problems in children
      living in remote Far North Queensland (FNQ). DESIGN, SETTING AND PARTICIPANTS:
      Retrospective review of the FNQ Paediatric Outreach Service's Medical Director
      database for the period June 2001 to February 2006. Three subpopulations were
      compared: children from predominantly Aboriginal communities, predominantly
      Torres Strait Islander communities, and other communities. All children referred
      to the service during the study period were reviewed. MAIN OUTCOME MEASURES:
      Number of children seen and common diagnoses. RESULTS: 3562 children were
      referred during the study period, and a total of 3932 diagnoses were made; 56% of
      the paediatric population of the Aboriginal communities and 23% of the paediatric
      population of Torres Strait Islander communities were seen. Of 40 separate
      diseases/health problems reviewed, the three most common reasons for presentation
      were chronic suppurative otitis media, suspected child abuse and neglect, and
      failure to thrive. In the paediatric population of Aboriginal communities, the
      prevalence of fetal alcohol spectrum disorder was at least 15/1000 (1.5%), and in
      Torres Strait Islander children, rheumatic heart disease prevalence was at least
      6/1000 (0.6%). Rheumatic fever rates were among the highest in Australia.
      CONCLUSION: Rates of preventable complex and chronic health problems in
      Aboriginal and Torres Strait Islander children in remote FNQ are alarmingly high.
      Areas requiring urgent public health intervention include alcohol-related
      conditions and rheumatic fever.

PMID- 17516900
TI  - The International Covenant on Economic, Social and Cultural Rights and the right
      to health: is Australia meeting its obligations to Aboriginal peoples?
AB  - There is evidence that Australia is not meeting its obligations to Aboriginal and
      Torres Strait Islander peoples for their right to the "highest attainable
      standard" of health, required under the International Covenant on Economic,
      Social and Cultural Rights (ICESCR). Poor access to primary health care for
      Aboriginal peoples and substantial shortfalls in government spending to address
      this are in violation of the ICESCR. Aboriginal and Torres Strait Islander
      peoples' share of the universal health coverage expenditure offered to all
      Australians is less per person than for other Australians. The failure to monitor
      the provision of mainstream health services to Aboriginal peoples and inequitable
      distribution of health facilities and services compound these violations.
      Equality in health between Indigenous and non-Indigenous Australians is
      achievable, but not until the shortfall in health services expenditure for
      Indigenous Australians is addressed.

PMID- 17516901
TI  - Indigenous health: effective and sustainable health services through continuous
      quality improvement.
AB  - The Australian government's Healthy for Life program is supporting capacity
      development in Indigenous primary care using continuous quality improvement (CQI)
      techniques. An important influence on the Healthy for Life program has been the
      ABCD research project. The key features contributing to the success of the
      project are described. The ABCD research project: uses a CQI approach, with an
      ongoing cycle of gathering data on how well organisational systems are
      functioning, and developing and then implementing improvements; is guided by
      widely accepted principles of community-based research, which emphasise
      participation; and adheres to the principles and values of Indigenous health
      research and service delivery. The potential for improving health outcomes in
      Aboriginal and Torres Strait Islander communities using a CQI approach should be
      strengthened by clear clinical and managerial leadership, supporting service
      organisations at the community level, and applying participatory-action
      principles.

PMID- 17516902
TI  - Overseas-trained doctors in Aboriginal and Torres Strait Islander health
      services: many unanswered questions.
AB  - Aboriginal and Torres Strait Islander health services are heavily dependent on
      overseas-trained doctors (OTDs). These OTDs are increasingly from countries with
      variable English language and educational equivalency compared with locally
      trained doctors. Aboriginal and Torres Strait Islander health services create
      particular demands for all doctors, such as negotiating "cultural domains" and
      acknowledging the contribution of Aboriginal health workers. Little is known
      about the roles and experience of OTDs in health service provision in Indigenous
      communities. Barriers to effective research into the experience of OTDs include
      privacy legislation and a lack of standardised data. Researching the narratives
      of OTDs in Indigenous health services offers an opportunity to explore the
      diversity and complexity of the cultural interfaces in health service provision.

PMID- 17516903
TI  - Town or country: which is best for Australia's Indigenous peoples?
AB  - Some commentators suggest that the poor health of Australia's Indigenous
      population is due to misguided ideology-driven policy that has forced people to
      live in remote communities, preventing them from benefiting from the mainstream
      economy. The evidence shows that the poor health status of Indigenous people is
      found in all areas where they live and that, on some indicators, living in remote
      areas has health benefits. Government policies aimed at relocating Indigenous
      people from their traditional lands are not supported by evidence, and may
      further entrench Indigenous disadvantage.

PMID- 17516904
TI  - Implications of land rights reform for Indigenous health.
AB  - In August 2006, the Aboriginal Land Rights (Northern Territory) Amendment Bill
      2006 (Cwlth) was passed into law, introducing, among other things, a system of 99
      year leases over Indigenous townships. The leasing scheme will diminish the
      control that traditional owners previously exercised over their lands. This is at
      odds with research indicating that control over land is a positive influence on
      Indigenous health.

PMID- 17516905
TI  - Why "culturally safe" health care?
AB  - People need to feel like themselves and believe that the health care is connected
      to their lives.

PMID- 17516906
TI  - The development of the First Nations, Inuit and Metis medical workforce.
AB  - Indigenous people make up more than 4% of the Canadian population, but less than
      0.25% of the physicians. National initiatives are being undertaken to increase
      the representation of First Nations, Inuit, and Metis people in the medical
      workforce. This is a necessary step in developing a health care system that is
      culturally safe and responsive - one step towards equity in health for First
      Nations, Inuit, and Metis people. Initiatives focus on recruitment and retention
      of indigenous physicians, and development of a curriculum framework to ensure all
      physicians can provide culturally safe care.

PMID- 17516907
TI  - Strengthening Maori participation in the New Zealand health and disability
      workforce.
AB  - Substantial progress has been made in Maori health and disability workforce
      development in the past 15 years. Key factors in successful programs to increase
      Maori health workforce recruitment and retention include Maori leadership,
      mentorship and peer support; and comprehensive support within study programs and
      in the transitions between school, university and work. The interventions to date
      provide a strong basis for ongoing action to address inequities in Maori health
      workforce participation, and are likely to be relevant to health workforce
      development approaches for other indigenous peoples.

PMID- 17516908
TI  - Reform in Australian medical schools: a collaborative approach to realising
      Indigenous health potential.
AB  - The Australian medical education system is at a critical juncture in relation to
      what and how it delivers for Aboriginal and Torres Strait Islander health. Since
      2004, three key organisations concerned with medical education have worked to
      provide a toolkit for implementation of sustainable reform within medical
      schools. The aim is a medical workforce trained in Indigenous health, and more
      Aboriginal and Torres Strait Islander doctors, leading to better health for
      Australia's Indigenous peoples.

PMID- 17516909
TI  - Training Indigenous doctors for Australia: shooting for goal.
AB  - Advocates, mentors and leaders in Indigenous health are emerging from our medical
      schools.

PMID- 17516910
TI  - We walk together as friends: the Shalom Gamarada Ngiyani Yana residential
      scholarship program.

PMID- 17516912
TI  - Role of vitronectin and fibronectin receptors in oral mucosal and dermal
      myofibroblast differentiation.
AB  - BACKGROUND INFORMATION: The activation of fibroblasts into myofibroblasts is a
      crucial event in healing that is linked to remodelling and scar formation,
      therefore we determined whether regulation of myofibroblast differentiation via
      integrins might affect wound healing responses in populations of patient-matched
      HOFs (human oral fibroblasts) compared with HDFs (human dermal fibroblasts).
      RESULTS: Both the HOF and HDF cell types underwent TGF-beta1 (transforming growth
      factor-beta1)-induced myofibroblastic differentiation [upregulation of the
      expression of alpha-sma (alpha-smooth muscle actin)], although analysis of
      unstimulated cells indicated that HOFs contained higher basal levels of alpha-sma
      than HDFs (P<0.05). Functional blocking antibodies against the integrin subunits
      alpha 5 (fibronectin) or alpha v (vitronectin) were used to determine whether the
      effects of TGF-beta1 were regulated via integrin signalling pathways. alpha-sma
      expression in both HOFs and HDFs was down-regulated by antibodies against both
      alpha 5 and alpha v. Functionally, TGF-beta1 inhibited cell migration in an in
      vitro wound model and increased the contraction of collagen gels. Greater
      contraction was evident for HOFs compared with HDFs, both with and without
      stimulation by TGF-beta1 (P<0.05). When TGF-beta1-stimulated cells were incubated
      with blocking antibodies against alpha 5 and alpha v, gel contraction was
      decreased to that of non-stimulated cells; however, blocking alpha v or alpha 5
      could not restore cellular migration in both HOFs and HDFs. CONCLUSIONS: Despite
      intrinsic differences in their basal state, the cellular events associated with
      TGF-beta1-induced myofibroblastic differentiation are common to both HOFs and
      HDFs, and appear to require differential integrin usage; up-regulation of alpha
      sma expression and increases in collagen gel contraction are vitronectin- and
      fibronectin-receptor-dependent processes, whereas wound re-population is not.

PMID- 17516913
TI  - Inhibition of MMP-2 gelatinolysis by targeting exodomain-substrate interactions.
AB  - MMP-2 (matrix metalloproteinase 2) contains a CBD (collagen-binding domain),
      which is essential for positioning gelatin substrate molecules relative to the
      catalytic site for cleavage. Deletion of the CBD or disruption of CBD-mediated
      gelatin binding inhibits gelatinolysis by MMP-2. To identify CBD-binding sites on
      type I collagen and collagen peptides with the capacity to compete CBD binding of
      gelatin and thereby inhibit gelatinolysis by MMP-2, we screened a one-bead one
      peptide combinatorial peptide library with recombinant CBD as bait. Analyses of
      sequences from the CBD-binding peptides pointed to residues 715-721 in human
      alpha1(I) collagen chain as a binding site for CBD. A peptide (P713) including
      this collagen segment was synthesized for analyses. In SPR (surface plasmon
      resonance) assays, the CBD and MMP-2(E404A), a catalytically inactive MMP-2
      mutant, both bound immobilized P713 in a concentration-dependent manner, but not
      a scrambled control peptide. Furthermore, P713 competed gelatin binding by the
      CBD and MMP-2(E404A). In control assays, neither of the non-collagen binding
      alkylated CBD or MMP-2 with deletion of CBD (MMP-2DeltaCBD) bound P713.
      Consistent with the exodomain functions of the CBD, P713 inhibited approximately
      90% of the MMP-2 gelatin cleavage, but less than 20% of the MMP-2 activity on a
      peptide substrate (NFF-1) which does not require the CBD for cleavage. Confirming
      the specificity of the inhibition, P713 did not alter MMP-2DeltaCBD or MMP-8
      activities. These experiments identified a CBD-binding site on type I collagen
      and demonstrated that a corresponding synthetic peptide can inhibit hydrolysis of
      type I and IV collagens by competing CBD-mediated gelatin binding to MMP-2.

PMID- 17516914
TI  - Design of fluorescence resonance energy transfer (FRET)-based cGMP indicators: a
      systematic approach.
AB  - The intracellular signalling molecule cGMP regulates a variety of physiological
      processes, and so the ability to monitor cGMP dynamics in living cells is highly
      desirable. Here, we report a systematic approach to create FRET (fluorescence
      resonance energy transfer)-based cGMP indicators from two known types of cGMP
      binding domains which are found in cGMP-dependent protein kinase and
      phosphodiesterase 5, cNMP-BD [cyclic nucleotide monophosphate-binding domain and
      GAF [cGMP-specific and -stimulated phosphodiesterases, Anabaena adenylate
      cyclases and Escherichia coli FhlA] respectively. Interestingly, only cGMP
      binding domains arranged in tandem configuration as in their parent proteins were
      cGMP-responsive. However, the GAF-derived sensors were unable to be used to study
      cGMP dynamics because of slow response kinetics to cGMP. Out of 24 cGMP
      responsive constructs derived from cNMP-BDs, three were selected to cover a range
      of cGMP affinities with an EC50 between 500 nM and 6 microM. These indicators
      possess excellent specifity for cGMP, fast binding kinetics and twice the dynamic
      range of existing cGMP sensors. The in vivo performance of these new indicators
      is demonstrated in living cells and validated by comparison with cGMP dynamics as
      measured by radioimmunoassays.

PMID- 17516915
TI  - Peroxisome-proliferator-activated receptors and the control of levels of
      prostaglandin-endoperoxide synthase 2 by arachidonic acid in the bovine uterus.
AB  - Arachidonic acid is a potential paracrine agent released by the uterine
      endometrial epithelium to induce PTGS2 [PG (prostaglandin)-endoperoxide synthase
      2] in the stroma. In the present study, bovine endometrial stromal cells were
      used to determine whether PTGS2 is induced by arachidonic acid in stromal cells,
      and to investigate the potential role of PPARs (peroxisome-proliferator-activated
      receptors) in this effect. Arachidonic acid increased PTGS2 levels up to 7.5-fold
      within 6 h. The cells expressed PPARalpha and PPARdelta (also known as PPARbeta)
      (but not PPARgamma). PTGS2 protein level was increased by PPAR agonists,
      including polyunsaturated fatty acids, synthetic PPAR ligands, PGA1 and NSAIDs
      (non-steroidal anti-inflammatory drugs) with a time course resembling that of
      arachidonic acid. Use of agonists and antagonists indicated PPARalpha (but not
      PPARdelta or PPARgamma) was responsible for PTGS2 induction. PTGS2 induction by
      arachidonic acid did not require PG synthesis. PTGS2 levels were increased by the
      PKC (protein kinase C) activators 4beta-PMA and PGF(2alpha), and the effects of
      arachidonic acid, NSAIDs, synthetic PPAR ligands and 4beta-PMA were blocked by
      PKC inhibitors. This is consistent with PPAR phosphorylation by PKC. Induction of
      PTGS2 protein by 4beta-PMA in the absence of a PPAR ligand was decreased by the
      NF-kappaB (nuclear factor kappaB) inhibitors MG132 and parthenolide, suggesting
      that PKC acted through NF-kappaB in addition to PPAR phosphorylation. Use of NF
      kappaB inhibitors allowed the action of arachidonic acid as a PPAR agonist to be
      dissociated from an effect through PKC. The results are consistent with the
      hypothesis that arachidonic acid acts via PPARalpha to increase PTGS2 levels in
      bovine endometrial stromal cells.

PMID- 17516916
TI  - Production of plasmid DNA encoding human hepatocyte growth factor for gene
      therapy.
AB  - pUDK-HGF, recombinant plasmid DNA encoding human HGF (hepatocyte growth factor),
      is a potential agent for gene therapy of ischaemic disease. Production of pUDK
      HGF is essential for its clinical application. In the present paper, a large
      scale manufacturing process was developed, including fermentation, cell harvest,
      alkaline lysis, capturing plasmid DNA with Q-Sepharose XL chromatography, size
      exclusion chromatography on a Sephacryl S1000 column and refining with Source 15Q
      anion-exchange chromatography. The quality criteria of pUDK-HGF such as purity,
      concentration, homogeneity, residual RNA, chromosomal DNA, contaminated protein,
      endotoxin and HGF expression efficacy all were analysed and met the requirements
      for pharmaceutical-grade plasmid DNA.

PMID- 17516918
TI  - Detection and quantification of affinity ligand leaching and specific antibody
      fragment concentration within chromatographic fractions using surface plasmon
      resonance.
AB  - Rapid analyses of chromatographic steps within a biopharmaceutical manufacturing
      process are often desirable to evaluate column performance, provide mass balance
      data and to permit accurate calculations of yields and recoveries. Using SPR
      (surface plasmon resonance) biosensor (Biacore) technology, we have developed a
      sandwich immunoassay to quantify polyclonal anti-digoxin Fab fragments used for
      the production of the FDA (Food and Drug Administration)-approved biotherapeutic
      DigiFab. The results show that specific Fab may be quantified in all affinity
      process streams and accurate yield and mass balance data calculated. Control
      experiments using sheep Fab and Fc indicate that the assay is specific to
      DigiFab. The quantification of potential leached ligand within chromatographic
      fractions may also be technically challenging, particularly when low-molecular
      mass ligands are covalently coupled with an affinity absorbent. Typical methods
      to assess ligand leakage such as DDMA (digoxin-dicarboxymethoxylamine; digoxin
      analogue) often involve the use of labelled ligands and relatively complex and
      labour-intensive analytical techniques. Using the same analytical methodologies,
      an assay to detect leached or eluted ligand off the column was developed. The
      results indicate minimal levels of leached ligand in all chromatographic
      fractions, with total levels of leached DDMA calculated to be 1.52 microg. This
      is less than 0.01% of the total amount of DDMA coupled with the laboratory-scale
      affinity column. The SPR methods described in the present study may be applicable
      for the rapid in-process analysis of specific polyclonal Fab fragments (within a
      polyclonal mixture) and to rapidly assess leakage of small molecule ligands
      covalently attached to chromatographic supports.

PMID- 17516919
TI  - A novel thrombopoietin-stem-cell factor fusion protein possesses enhanced
      potential in stimulating megakaryocyte proliferation and differentiation.
AB  - TPO (thrombopoietin) and SCF (stem-cell factor) are functionally related
      cytokines with overlapping but distinct haematopoietic effects. In the present
      study, a novel TPO-SCF fusion protein that combined the complementary biological
      effects of TPO and SCF into a single molecule was expressed in, and purified
      from, Sf9 [Spodoptera frugiperda (fall armyworm)] insect cells. The specific
      activity of rhTPO (recombinant human TPO)-SCF in megakaryoblastic Mo7e cell
      proliferation assays was 2.90+/-0.35 x 10(7) units/micromol, approx. 1.7 times as
      high as that of rhTPO. The specific activity of rhTPO-SCF in TF-1 cells
      proliferation assays was 7.10+/-0.95 x 10(6) units/micromol, approx. 1.2 times as
      high as that of rhSCF (recombinant human SCF). In a megakaryocyte-colony-forming
      assay using human peripheral-blood CD34(+) cells, the SCF moiety of rhTPO-SCF
      worked in a synergistic way to augment the colony number and exhibited a higher
      potential to stimulate megakaryocyte colony growth. According to the results of
      EMSA (electrophoretic mobility-shift assay) and semi-quantitative RT (reverse
      transcriptase)-PCR, the synergistic effects of the SCF moiety were also reflected
      in increased STAT5 (signal transducer and activator of transcription 5) DNA
      binding and enhanced up-regulation of p21 expression in Mo7e cells treated by
      rhTPO-SCF, suggesting that rhTPO-SCF could be more potent in promoting
      megakaryocyte proliferation and differentiation.

PMID- 17516921
TI  - A darker side to p53.

PMID- 17516922
TI  - Walking in the footsteps of giants: melanocortins and human pigmentation, a
      historical perspective.

PMID- 17516923
TI  - Myosins in melanocytes: to move or not to move?
AB  - The actin network has been implicated in the intracellular transport and
      positioning of the melanosomes, organelles that are specialized in the
      biosynthesis and the storage of melanin. It contributes also to molecular
      mechanisms that underlie the intracellular membrane dynamics and thereby can
      control the biogenesis of melanosomes. Two mechanisms for actin-based movements
      have been identified: one is dependent on the motors associated to actin namely
      the myosins; the other is dependent on actin polymerization. This review will
      focus on to the role of the actin cytoskeleton and myosins in the transport and
      in the biogenesis of melanosomes. Myosins involved in membrane traffic are
      largely seen as transporters of organelles or membrane vesicles containing cargos
      along the actin networks. Yet increasing evidence suggests that some of the
      myosins contribute to the dynamics of internal membrane by using other
      mechanisms. The role of the myosins and the different molecular mechanisms by
      which they contribute or may contribute to the distribution, the movement and the
      biogenesis of the melanosomes in epidermal melanocytes and retinal pigmented
      epithelial (RPE) cells will be discussed.

PMID- 17516924
TI  - Melanoma invasion - current knowledge and future directions.
AB  - The acquisition of invasive behaviour is the key transition in the progression of
      benign melanocyte hyperplasia to life threatening melanoma. Understanding this
      transition and the mechanisms of invasion are the key to understanding why
      malignant melanoma is such a devastating disease and will aid treatment
      strategies. Underlying the invasive behaviour is increased cell motility caused
      by changes in cytoskeletal organization and altered contacts with the extra
      cellular matrix (ECM). In addition, changes in the interactions of melanoma cells
      with keratinocytes and fibroblasts enable them to survive and proliferate outside
      their normal epidermal location. Proteomic and genomic initiatives are greatly
      increasing our knowledge of which gene products are deregulated in invasive and
      metastatic melanoma; however, the next challenge is to understand how these genes
      promote the invasion of melanoma cells. In recent years new models have been
      developed that more closely recapitulate the conditions of melanoma invasion in
      vivo. It is hoped that these models will give us a better understanding of how
      the genes implicated in melanoma progression affect the motility of melanoma
      cells and their interactions with the ECM, stromal cells and blood vessels. This
      review will summarise our current understanding of melanoma invasion and focus on
      the new model systems that can be used to study melanoma.

PMID- 17516925
TI  - The tyrosinase enhancer is activated by Sox10 and Mitf in mouse melanocytes.
AB  - The terminal differentiation of melanocytes is associated with the
      transcriptional activation of genes responsible for pigment production such as
      tyrosinase. Pigment cell-specific transcription factors, such as Mitf, as well as
      specific proximal and distal regulatory elements (DRE) are implicated in the
      tight control of tyrosinase expression during development and adulthood. Proper
      tyrosinase expression in melanocytes depends upon the presence of a DRE that is
      located at -15 kb and provides enhancer activity via a central element termed
      core-enhancer. In this report, we show that the transcription factors Sox10, Mitf
      and USF-1 are able to activate the core-enhancer in luciferase reporter assays.
      Comparative sequence analysis identified evolutionarily motifs resembling Sox10
      binding sites that were required for full enhancer activity in melanoma cells and
      in tyrosinase::lacZ transgenic mice. Sox10 was able to bind the DRE in vitro and
      mutation of the conserved motifs abolished the enhancer transactivation mediated
      by Sox10. In addition, two highly conserved CAGCTG E-box motifs were identified
      that were also required for enhancer activity and for transactivation by Mitf.
      The results suggest that Sox10 directly, and Mitf, most likely indirectly,
      activate the tyrosinase enhancer, underlining the contribution of Sox10 to
      tyrosinase gene regulation in melanocytes.

PMID- 17516926
TI  - Evolutionary sequence comparison of the Mitf gene reveals novel conserved
      domains.
AB  - The microphthalmia-associated transcription factor (MITF) is a member of the MYC
      family of basic helix-loop-helix leucine zipper transcription factors. The
      corresponding gene was initially discovered in the mouse based on mutations which
      affect the development of several different cell types, including melanocytes and
      retinal pigment epithelium cells. Subsequently, it was shown to be associated
      with deafness and hypo-pigmentation disorders in humans. More recently, the gene
      has been shown to be critical in melanoma formation and to play a role in
      melanocyte stem cell maintenance. Thus, the mouse Mitf gene represents an
      important model system for the study of human disease as well as an interesting
      model for the study of transcription factor function in the organism. Here we use
      the evolutionary relationship of Mitf genes from numerous distantly related
      species, including vertebrates and invertebrates, to identify novel conserved
      domains in the Mitf protein and regions of possible functional importance in the
      3' untranslated region. We also characterize the nine different 5' exons of the
      Mitf gene and identify a new 5' exon in the Drosophila Mitf gene. Our analysis
      sheds new light on the conservation of the Mitf gene and protein and opens the
      door for further functional analysis.

PMID- 17516927
TI  - Informatic and genomic analysis of melanocyte cDNA libraries as a resource for
      the study of melanocyte development and function.
AB  - As part of the RIKEN mouse encyclopedia project, two cDNA libraries were prepared
      from melanocyte-derived cell lines, using techniques of full-length clone
      selection and subtraction/normalization to enrich for rare transcripts. End
      sequencing showed that these libraries display over 83% complete coding sequence
      at the 5' end and 96-97% complete coding sequence at the 3' end. Evaluation of
      the libraries, derived from B16F10Y tumor cells and melan-c cells, revealed that
      they contain clones for a majority of the genes previously demonstrated to
      function in melanocyte biology. Analysis of genomic locations for transcripts
      revealed that the distribution of melanocyte genes is non-random throughout the
      genome. Three genomic regions identified that showed significant clustering of
      melanocyte-expressed genes contain one or more genes previously shown to regulate
      melanocyte development or function. A catalog of genes expressed in these
      libraries is presented, providing a valuable resource of cDNA clones and sequence
      information that can be used for identification of new genes important for
      melanocyte development, function, and disease.

PMID- 17516928
TI  - A mouse model of Waardenburg syndrome type IV resulting from an ENU-induced
      mutation in endothelin 3.
AB  - A line of mutant mice (114-CH19) exhibiting white spotting and preweaning
      lethality was identified during an N-ethyl-N-nitrosourea (ENU) mutagenesis
      screen. The trait segregated as a semidominant bellyspot with reduced penetrance.
      Homozygous mutant mice showed preweaning lethality, and exhibited white spotting
      over the majority of the body surface, with pigmented patches remaining around
      the pinnae, eyes and tail. Linkage analysis localized 114-CH19 on mouse
      chromosome 2, suggesting endothelin 3 (Edn3) as a candidate gene. Sequence
      analysis of Edn3 identified a G > A transversion that encodes an arginine to
      histidine substitution (R96H). This mutation is predicted to disrupt furin
      mediated proteolytic cleavage of pro-endothelin that is necessary to form
      biologically active EDN3. This mutation is novel among human and mouse EDN3
      mutants, is the first reported EDN3 ENU mutant, and is the second reported EDN3
      point mutation. This study demonstrates the power of using ENU mutagenesis
      screens to generate new animal models of human disease, and expands the spectrum
      of EDN3 mutant alleles.

PMID- 17516929
TI  - Confirmation of a BRAF mutation-associated gene expression signature in melanoma.
AB  - Mutations in the BRAF oncogene occur in the majority of melanomas, leading to the
      activation of the mitogen-activated protein kinase pathway and the transcription
      of downstream effectors. As BRAF and its effectors could be good melanoma therapy
      targets, defining the repertoire of genes that are differentially regulated
      because of BRAF mutational activation is an important objective. Towards this
      goal, we and others have attempted to determine whether a BRAF mutation
      associated gene expression profile exists. Results have been mixed, with some
      groups reporting a BRAF-signature and another group not. Here we resolve this
      issue and confirm that while gene-by-gene correlations fail to reveal a specific
      gene(s) whose expression correlates with BRAF status, a BRAF signature can be
      distinguished by analysis of global expression patterns. Specifically, we have
      here applied support vector machine (SVM) analysis to Affymetrix microarray data
      from a panel of 63 melanoma cell lines. SVMs found a BRAF signature in training
      samples and predicted BRAF mutation status with high accuracy (AUC=0.840) in the
      remaining samples. We verified this is a generalized BRAF signature by repeating
      the analysis in three published microarray datasets, and again found that SVMs
      predicted BRAF mutation well (Philadelphia: AUC=0.788; Zurich: AUC=0.688;
      Mannheim: AUC=0.686). An ensemble of 300 SVMs trained on our data also predicted
      BRAF mutation status in two of the three published datasets (Philadelphia
      AUC=0.778; Zurich AUC=0.719; Mannheim AUC=0.564). Taken together, these data
      support the existence of a BRAF mutation-specific expression signature.

PMID- 17516930
TI  - High levels of melanin-related metabolites in plasma from pink-eyed dilution
      mice.

PMID- 17516931
TI  - Polymorphisms in the genes for oculocutaneous albinism type 1 and type 4 in the
      German population.

PMID- 17516935
TI  - Inorganic phosphate transport in matrix vesicles from bovine articular cartilage.
AB  - AIMS: In mineralizing tissues such as growth plate cartilage extracellular
      organelles derived from the chondrocyte membrane are present. These matrix
      vesicles (MV), possess membrane transporters that accumulate Ca(2+) and inorganic
      phosphate (P(i)), and initiate the formation of hydroxyapatite crystals. MV are
      also present in articular cartilage, and hydroxyapatite crystals are believed to
      promote cartilage degradation in osteoarthritic joints. This study characterizes
      P(i) transport in MV derived from articular cartilage. METHODS: Matrix vesicles
      were harvested from collagenase digests of bovine articular cartilage by serial
      centrifugation. P(i) uptake by MV was measured using radioactive phosphate
      ((33)[P]HPO(4)(2-)). The Na(+) dependence, pH sensitivity and effects of P(i)
      analogues that inhibit P(i) transport were determined. RESULTS: P(i) uptake was
      temperature-sensitive and comprised Na(+)-dependent and Na(+)-independent
      components. The Na(+)-dependent component saturated at high extracellular P(i)
      concentrations, with a K(m) of 0.16 mM. In Na(+)-free solutions, uptake did not
      fully saturate implying that carrier-mediated uptake is supplemented by a
      diffusive pathway. Uptake was inhibited by phosphonoacetate and arsenate,
      although a fraction of Na(+)-independent P(i) uptake persisted. Total P(i) uptake
      was maximal at pH 6.5, and reduced at more acidic or alkaline values,
      representing inhibition of both components. CONCLUSION: These properties are
      highly similar to those of P(i) uptake by chondrocytes, suggesting that MV
      inherit P(i) transporters of the chondrocyte membrane from which they are
      derived. Na(+)-independent P(i) uptake has not previously been described in MV
      from growth plate cartilage and is relatively uncharacterized, but warrants
      further attention in articular cartilage, given its likely role in initiating
      inappropriate mineral formation.

PMID- 17516936
TI  - Effects of dietary scFOS on immunoglobulins in colostrums and milk of bitches.
AB  - Fructo-oligosaccharides (scFOS) are prebiotic ingredients that improve protection
      against pathogens probably through promoting the growth of gastrointestinal
      bacteria-like Bifidobacteria and Lactobacilli: this stimulation may lead to a
      better development of immune repertoire and/or stimulation of the local immune
      response. According to the existence of the immune entero-mammary link, we were
      wondering if the dietary supplementation with scFOS could enhance the mucosal
      immunoglobulin level in mammary secretions. Results in this study show that
      bitches supplemented with scFOS exhibit higher colostrum and milk IgM content
      without concomitant effect on IgG1, IgG2 and IgA. In addition, intranasally
      immunized puppies exhibited a trend to higher Bordetella bronchiseptica-specific
      IgM immune response. The dietary supplementation with scFOS increased the IgM
      level in colostrums and milk of bitches by mechanisms which remain to be
      elucidated.

PMID- 17516937
TI  - Influence of deoxynivalenol on the D-glucose transport across the isolated
      epithelium of different intestinal segments of laying hens.
AB  - Deoxynivalenol (DON) decreases glucose absorption in the proximal jejunum of
      laying hens in vitro and this effect is apparently mediated by the inhibition of
      the sodium D-glucose co-transporter. DON could modulate the sugar transport of
      other intestinal regions of chickens. For this purpose, we have measured the
      effects of DON on the Na(+) D-glucose co-transporter, by addition of DON after
      and before a glucose addition in the isolated epithelium from chicken duodenum,
      jejunum, ileum, caecum and colon by using the Ussing chamber technique in the
      voltage clamp technique. The data showed in all segments of the gut that the
      addition of D-glucose on the mucosal side produced an increase in the current
      (Isc) compared with the basal values, the Isc after glucose addition to the small
      intestine was greater than the Isc of the large intestine compared with the basal
      values, specially of the jejunum (p < 0.002), indicating that the jejunum is the
      segment that is the best prepared for Na(+)-D-glucose co-transport. Further
      addition of 10 microg DON/ml to the mucosal solution decreased the Isc in all
      segments and the Isc returned to the basal value, especially in the duodenum and
      mid jejunum (p < 0.05). In contrast, the addition of 5 mmol D-glucose/l on the
      mucosal side after incubation of the tissues with DON in all segments had no
      effect on the Isc (p > 0.05), suggesting that DON previously inhibited the Na(+)D
      glucose co-transport. The blocking effects of DON in duodenum and jejunum were
      greater than the other regions of the gut. It can be concluded that the small
      intestine of laying hens has the most relevant role in the carrier mediated
      glucose transport and the large intestine, having non-significant capacity to
      transport sugars, appears to offer a minor contribution to glucose transport
      because the surface area is small. The effect of D-glucose on the Isc was
      reversed by DON in all segments, especially in the duodenum and jejunum,
      suggesting that DON entirely inhibited Na(+)-D-glucose co-transport. This finding
      indicates that the inhibition of Na(+) co-transport system in all segments could
      be an important mode of action for DON toxicity of hens.

PMID- 17516938
TI  - Use of two different dietary energy and protein contents to define nutritive
      requirements of lactating buffalo cows.
AB  - Two total mixed rations, differing in energy and protein concentrations (diet A:
      6.1 MJ/kg DM of NE(l), 112.5 g/kg DM of metabolizable protein, MP, and 101.7 g of
      protein digestible at the intestinal level, PDI, vs. diet B: 6.4 MJ, 95.1 g of
      MP, 78.9 g of PDI) were administered ad libitum for 1 year to two groups of 12
      buffaloes in which the partial monthly turnover of animals allowed the lactation
      stage to be maintained close to 160 days. The diets were formulated to obtain,
      with a daily intake of about 15.5 kg of DM, a balanced energy supply but an
      excess of protein (diet A); the opposite occurred with diet B. The average dry
      matter intake recorded during the trial was 14.5 kg for diet A and 15.0 kg for
      diet B. Milk production was similar for both groups (7.94 kg vs. 7.95 kg). The
      diet with a higher protein concentration brought about a significant increase in
      protein, casein and non-protein nitrogen contents in the milk. A significant
      increase in milk fat percentage was observed when the animals were fed the diet
      with a higher energy concentration. The serum urea concentration (8.62 mm/l) of
      buffaloes fed diet A was outside the physiological range for lactating buffaloes.
      The energy and protein conversion efficiencies for milk production were more
      favourable when their supplies were balanced: 3.58 MJ of NE(l)/kg of FPCM for
      diet A; 2.50 g of MP or 2.07 g of PDI/g of protein milk for diet B. Moreover,
      when the requirements were satisfied, greater energy or protein supplies failed
      to induce significant changes in milk yield and quality. Finally, regarding the
      great differences between estimated MP requirements and those recorded during the
      trial, the authors suggest that the equations used in the CPM-Dairy software,
      formulated for dairy cows, are not applicable in buffaloes.

PMID- 17516939
TI  - Effect of captivity and mineral supplementation on body composition and mineral
      status of mustached bats (Pteronotus parnellii rubiginosus).
AB  - We investigated the whole-body crude nutrient (fat, protein, ash) and mineral
      (Ca, P, Mg, Na, K) composition of mustached bats of three different groups:
      animals from the wild (n = 6), and animals from captivity on an unsupplemented
      feeding regime of mealworms (n = 7), and on a feeding regime in which the
      mealworms were kept on a mineral substrate prior to feeding (n = 6). It was shown
      that mealworms from the mineral substrate had higher Ca contents than mealworms
      from the conventional substrates. In an earlier study, differences in bone
      mineral density had been found between the groups. These differences, however,
      were not reflected in differences in whole-body composition. Captive animals
      showed a larger variation in body weight and fat content, indicating potential
      shortcomings of the dietary and husbandry regime.

PMID- 17516940
TI  - Mineral absorption in the black rhinoceros (Diceros bicornis) as compared with
      the domestic horse.
AB  - To test whether mineral recommendations for horses are likely to guarantee
      adequate mineral provision for black rhinoceroses (Diceros bicornis), we
      investigated the apparent absorption (aA) of macro- and microminerals in eight
      black rhinoceroses from three zoological institutions in a total of 32 feeding
      trials with total faecal collection, with additional data from three unpublished
      studies (18 feeding trials). Feeds and faeces were analysed for Ca, P, Mg, Na, K,
      Fe, Mn, Cu, Zn and Co. The resulting aA coefficients, and the linear
      relationships of apparently absorbable dietary mineral content to total dietary
      mineral content [per 100 g dry matter (DM)], were compared with data for domestic
      horses. Rhinoceroses had significantly higher aA coefficients for Ca and Mg
      (because of a higher calculated 'true' absorption), and lower ones for Na and K
      (because of calculated higher endogenous faecal losses). High absorption
      efficiency for divalent cations is hypothesized to be an adaptation to a natural
      diet of particularly high Ca:P ratio (approximately 14:1); an effective removal
      of Ca from the ingesta guarantees sufficient P availability at the fermentation
      site in the hindgut. Higher faecal losses of Na and K are hypothesized to be
      linked to a higher faecal bulk per DM intake in black rhinoceroses as compared
      with horses because of a generally lower digestive efficiency. There were no
      relevant differences in the absorption patterns of microminerals. In particular,
      there were no discernable differences in Fe absorption within the rhinoceroses
      for diets with and without tannin supplementation. Several of the zoo diets
      assessed in this study were deficient in Cu, Mn or Zn, and most contained
      excessive levels of Fe when compared with horse requirements. The findings of
      this study indicate that differences in mineral absorption between occur even
      between species of similar digestive anatomy; that in particular, Ca absorption
      might vary between hindgut fermenters with Ca:P ratio in their natural diet; that
      Na might be a particularly limiting factor in the ecology of free-ranging
      rhinoceroses; that moderate doses of tannins do not seem to markedly influence
      mineral absorption; and that diets for captive animals should contain adequate,
      but not excessive mineral levels.

PMID- 17516941
TI  - Prediction of digestible energy content of extruded dog food by in vitro
      analyses.
AB  - The aim of this study was to develop a simple and reproducible in vitro method
      for predicting the apparent energy digestibility of dry extruded dog foods. The
      proposed method is based on the two-step multienzymatic incubation assay
      described by [Boisen, S., 1991: In Vitro Digestion for Pigs and Poultry, M. F.
      Fuller (ed.). CAB International, Wallingford, 135-146], with some modifications
      adapted to dogs' digestion characteristics. The method consisted in two
      consecutives incubations, first one during 2 h with pepsin (10 mg/g of food
      sample) in acid pH and second one during 4 h with pancreatin (100 mg/g of food
      sample). The undigested residue obtained was collected in a filtration unit and
      then dried and ashed. The in vitro percentage of organic matter disappearance (in
      vitro dOM) of 54 dry extruded commercial dog foods was determined and used as
      predictor of the in vivo apparent organic matter (in vivo dOM) and energy
      digestibility (in vivo dE) and digestible energy (DE) content. There was a close
      linear relationship between the in vivo dOM and dE [r(2) = 0.95, residual
      standard deviation (RSD) = 1.05 and coefficient of variation (CV) = 1.2%] and
      also between the in vitro and in vivo dOM (r(2) = 0.92, RSD = 1.38 and CV =
      1.6%), even if the in vitro dOM overestimated on average by 4% the in vivo dOM.
      When the in vitro dOM was used to predict the in vivo dE, the relationship
      between both variables was defined by the equation: in vivo dE (%) = -2.45 + 0.98
      +/- 0.04x in vitro dOM (%), (r(2) = 0.92, RSD = 1.25 and CV = 1.5%). In addition,
      a close relationship between the in vivo and predicted DE (estimated dE x gross
      energy determined calorimetrically) was found (r(2) = 0.97, RSD = 0.26 and CV =
      1.4%). The accuracy of DE content prediction using the proposed in vitro method
      was higher than that obtained when the DE content of the same set of samples was
      predicted by the equation proposed by the NRC (1985) (r(2) = 0.76, CV = 4.5%) and
      also slightly higher than that obtained when using the equation proposed by NRC
      (2006) (r(2) = 0.95, CV = 2.1%).

PMID- 17516942
TI  - Apparent nutrient digestibility and excreta quality in African grey parrots fed
      two pelleted diets based on coarsely or finely ground ingredients.
AB  - A feeding trial was performed to study the influence of particle size in extruded
      parrot pellets on apparent digestibility and excreta consistency and pH. Two test
      diets were alternately provided to eight African grey parrots according to a 2 x
      2 cross-over design. Both diets were similar in nutrient content and ingredient
      composition but differed in particle size of the composing particles of
      individual pellets. Apparent digestibility of macronutrients was studied using
      the total collection method. Next, the appearance of the excreta was studied by
      calculation of weight-surface ratio of individual excrements as an objective
      measurement of consistency. Last, excreta pH was measured directly on fresh
      excrements and on homogenized 10% excreta solutions. Neither apparent
      digestibility coefficients nor excreta pH values were significantly different in
      parrots fed the two diets. However, excreta consistency was significantly (p <
      0.05) more solid when fed the coarse diet than when fed with the finely ground
      diet. The results of this study suggest that excreta consistency can be improved
      through larger particle size, without adverse effects on nutritive value of the
      diet.

PMID- 17516943
TI  - Bone metabolism of milk goats and sheep during second pregnancy and lactation in
      comparison to first lactation.
AB  - Substantial losses of skeletal tissue occur during late pregnancy and lactation.
      The goal of the present study was to follow these changes in pregnant and
      lactating goats and sheep, compare these two species during their second
      lactation, and also compare the results to the first lactation. Blood samples
      were collected from 12 adult dairy goats (Saanen goat) and sheep (Ostfriesen milk
      sheep) monthly during gestation, 2 or 3 days postpartum (pp), 2 weeks pp, 4 weeks
      pp, and then monthly during lactation until 7 months after parturition. Total
      bone mineral content (BMC) and total bone mineral density (BMD) were quantified
      using peripheral quantitative computed tomography (pQCT) at the same intervals as
      the blood was taken. Bone resorption was assessed in serum using two different
      domains of the carboxyterminal telopeptide of type I collagen (ICTP and
      crosslaps). Bone formation was quantified in serum with osteocalcin (OC) and bone
      specific alkaline phosphatase (bAP). In addition, Ca and 1,25 dihydroxy vitamin D
      (VITD) were determined in serum. The same procedure was done during the first and
      second gestation and lactation. Mean ICTP and crosslaps concentrations of the two
      animal species showed an increase in the last month of gestation. In contrast,
      mean OC concentrations decreased slowly from the 2nd month of pregnancy until the
      first week pp. Also mean bAP activities showed a similar time course. Total BMC
      and BMD decreased until the first week pp in both species. Afterwards, BMC
      increased again during lactation. BMD levels of sheep and goats returned to
      prepartum levels during lactation. Vitamin D concentrations peaked in the first
      week pp. Only VITD concentrations in goats stayed elevated compared with
      prepartum values throughout the whole lactation during the second lactation.
      Around parturition and at the beginning of lactation, the bone resorptive phase
      of bone remodelling is accelerated, but is uncoupled from the process of bone
      formation. The mineral decrease in bone of these lactating animals seems to be
      reversible. Since during lactation, bone remodelling has bone resorption and
      formation phases tightly coupled. Interestingly, in these species, the bone loss
      in the second pregnancy and lactation measured with BMC and BMD is not as
      prominent as in the first lactation, but shows almost the same course, although
      the animals gave more milk in the second lactation. It seems that the organism
      adapts to the circumstances more easily in the second lactation compared to the
      first lactation in these two species.

PMID- 17516944
TI  - Subacute rumen acidosis in lactating cows: an investigation in intensive Italian
      dairy herds.
AB  - Subacute rumen acidosis (SARA) represents one of the most important metabolic
      disorders in intensive dairy farms that affects rumen fermentations, animal
      welfare, productivity and farm profitability. The aim of the present study was to
      study the occurrence of SARA in intensive Italian dairy herds and to determine
      the relationship between diet composition, ruminal pH and short chain fatty acids
      (SCFA) concentration. Ten commercial dairy herds were investigated; twelve cows
      in each herd were selected randomly among animal without clinical signs of
      disease, with good body condition and between 5 and 60 day-in-milk (DIM), to
      perform rumenocentesis and obtain rumen fluid. Ruminal pH was determined
      immediately after sampling and concentration of SCFA in ruminal fluid was
      determined on samples after storage. An other objective of this research was to
      study in detail the effects of rumenocentesis on animal health: this study could
      confirm the extreme validity of this technique as ruminal sampling. Results were
      subject to anova and correlation analysis using SIGMA STAT 2.03. The results
      indicated the presence of SARA in three herds (more than 33% cows with rumen pH <
      5.5), a critical situation (more than 33% cows with rumen pH < 5.8) in five farms
      and a normal rumen pH condition in two herds. In particular, dairy herds show on
      average SCFA concentration of 150, 145, 123 mmol/l for low pH, critical pH and
      normal pH herds respectively. There were not significant differences among diet
      composition even if herds with SARA showed a light discordance between initially
      chemistry composition and residual feed. In the affected herds it was not
      possible to understand the exact causes of SARA. Animal management seems to be
      one of the most important factors in developing SARA including total mixed ration
      preparation.

PMID- 17516945
TI  - Rice protein concentrate meal as potential dietary ingredient in practical diets
      for blackspot seabream (Pagellus bogaraveo).
AB  - The aim of this study was to evaluate the performances and the flesh quality of
      Pagellus bogaraveo fed with diets containing rice protein concentrate [RPC, 70%
      crude protein (CP) and 10% ether extract]. Three isoproteic and isoenergetic (CP
      47%, 22 MJ/kg DM) diets were formulated with an increasing level of RPC: 0%, 20%
      and 35%. The fish (mean weight 75 g) from the Messina Straits were randomly
      distributed in 12 tanks (3 diets x 4 replications, 10 fish/tank). The daily ratio
      (1.5% of the fish biomass) was updated every 15 days. Biomass gain showed an
      opposite trend to the RPC diet inclusion. No differences appeared in the somatic
      indexes. Differences appeared between fatty acid profiles of the dorsal muscle.
      Fatty acid of series n-6 increased and fatty acid of series n-3 decreased in
      fillets of fish fed with increasing levels of RPC. The inclusion of RPC in the
      diets, as a partial replacement of fish meal (20%), is possible without affecting
      the growth performance and fillet quality.

PMID- 17516946
TI  - Comparison between plasma and milk levels of leptin during pregnancy and
      lactation in cow, a relationship with beta-lactoglobulin.
AB  - Leptin gene is expressed in the mammary tissue and the expression of both leptin
      and its receptor changes significantly during pregnancy and lactation, with high
      levels during the first half of pregnancy and a decrease at delivery. The aim of
      this work was to investigate into leptin concentration in plasma and in milk
      during pregnancy and the first week after parturition in dairy cow and to analyze
      the correlation between leptin and beta-lactoglobulin (beta-LG) concentrations in
      plasma and in milk. The trial was conducted on six Holstein dairy cows, reared in
      the same environmental conditions and evaluated with similar body condition
      score, during the complete reproductive cycle from insemination to the delivery.
      Blood from the jugular vein and milk samples were collected at weekly intervals.
      Plasma leptin concentration showed a lower level (p < 0.05) at the beginning of
      pregnancy. Milk leptin concentration showed a higher level (p < 0.01) than plasma
      level from week 23 to week 29 of pregnancy. Plasma beta-LG concentrations were
      higher (p < 0.01) compared to plasma concentrations during the first part of
      pregnancy, then milk levels rise and become higher than plasma levels during the
      last weeks before dry period. A positive correlation (p < 0.01) was observed
      between leptin and beta-LG both in plasma and in milk profiles.

PMID- 17516947
TI  - Analysis of 4495 canine and feline uroliths in the Benelux. A retrospective
      study: 1994-2004.
AB  - From 1994 to 2004, Hill's Pet Nutrition received 4495 canine (65%) and feline
      (35%) uroliths from Benelux veterinary practitioners. They were sent to the
      Minnesota Urolith Center, USA for analysis. In 1994, 110 uroliths were analysed -
      85% from dogs - and in 2003, 1067 uroliths were analysed - 59% from dogs. During
      this period, substantial changes were observed in composition. In 1994, 77% of
      the cats had uroliths composed of struvite, and 12% had uroliths composed of
      calcium oxalate. In 2003, feline uroliths were composed of 32% struvite, and 61%
      calcium oxalate. The same evolution was observed in the dogs. In 1994, 51% of
      canine uroliths were composed of struvite, and 33% of calcium oxalate. In 2003,
      40% had struvite uroliths, and 46% had calcium oxalate uroliths. A significant
      effect of the size, the breed, and the gender were noticed in the dogs. The mean
      age of uroliths appearance was 7.3 years in the dogs and 7.2 years in the cats.
      The findings are similar to those previously published in the USA.

PMID- 17516948
TI  - Vegetable and animal food sorts found in the gastric content of Sardinian Wild
      Boar (Sus scrofa meridionalis).
AB  - Authors report results emerging from gastric content analysis from n. 96 wild
      boars hunted in Sardinia isle, during the hunting tide (2001-2005), from November
      to January. Mean pH of the gastric content was 3.77 +/- 0.69. Mean total capacity
      (TC) of each stomach was 1702 +/- 680 g. Mean Stuff ratio (CW/TC) between the
      content weight (CW) and stomachs TC was 0.45. Food categories found in animal
      stomachs were: 19 categories of vegetal species (Allium spp., Arbutus unedo,
      Arisarum vulgare, Avena fatua, Avena sativa, Castanea sativa, Ceratonia siliqua,
      Chamaerops umilis, Cichorium intybus, Hordeum sativum, Juniperus oxycedrus,
      Myrtus communis, Olea europea, Pirus amygdaliformis, Pistacia lentiscus, Quercus
      spp., Rhamnus alaternus, Triticum durum, Zea mais); 11 categories of animal
      species (Agriotes lineatus, Apodemus sylvaticus dicrurus, Chalcides chalcides,
      Chalcides ocellatus tiligugu, Crematogaster scutellaris, Forficula auricularia,
      Helix aspersa, Lumbricus terrestris, Ovis aries, Podarcis tiliguerta tiliguerta,
      Scolopendra cingulata); three categories were identified in general terms
      (insects larvae, hairs of mammals, feathers of birds). Food categories found in
      the stomach contents of Sus scrofa meridionalis confirm observations by other
      researchers who report the prevalence of vegetables in spite of animal food sorts
      in the wild boar diet in Italian regions.

PMID- 17516949
TI  - Use of Silybum marianum fruit extract in broiler chicken nutrition: influence on
      performance and meat quality.
AB  - The present study aimed at evaluating the effects of different doses of silymarin
      in diet on broiler performances and meat quality. For the trial, 180 male chicks
      (ROSS 508), were allocated in to three groups (S0, S40 and S80) of 60 animals
      each receiving a basal diet supplemented with 0 ppm, 40 ppm and 80 ppm of a
      sylimarin (provided by a dry extract of Silybum marianum fruits) respectively.
      During the trial feed consumption and live body weight were taken every 20 days.
      At the age of 40 and 60 days blood samples were taken in order to evaluate
      protein, aspartate aminotransferase, cholesterol, tryglicerides and uric acid. At
      the age of 60 days animals were slaughtered, dressing percentages were evaluated
      and samples of breast and meat were taken to evaluate chemical composition and
      susceptibility of lipid peroxidation by means of thiobarbituric acid reactive
      substances. Silymarin at the tested doses did not affect growth performances but
      slightly affected slaughtering yields negatively, no specific hepatoprotective
      effect was found. Treatments reduced lipid content of both breast and thigh and
      increased muscles resistance to oxidative stress.

PMID- 17516950
TI  - Glycaemic and insulinaemic responses to mechanical or thermal processed barley in
      horses.
AB  - This study was conducted to evaluate the effects of different barley processing
      techniques on the glycaemic and insulinaemic responses in horses. It was
      hypothesized that the changes in pre-caecal starch digestibility caused by barley
      processing would affect metabolic responses. Six horses were fed in random order:
      whole (WB), finely ground (FGB), steamed (SB), steam-flaked (SFB) and popped
      barley (PB). The total barley intake was adjusted to 630 g starch/horse/day (1.2
      1.5 g starch/kg BW/day). During a 10-day stabilization period, the horses also
      received 6 kg grass hay/horse/day. On the blood collection day, the horses were
      fed their test diet (exclusively barley), and blood samples were taken at defined
      times for glucose and insulin analysis. The degree of starch gelatinization (DG)
      in the untreated or thermally processed barley was analysed using the
      glucoamylase method. In general, barley feeding resulted in a significant
      increase in mean plasma glucose and insulin concentrations within 30-45 min after
      feeding. While the highest glucose and insulin responses occurred after intake of
      SFB with a DG of 28.7%, the changes in glucose and insulin were more pronounced
      with PB with a DG of 95.6%, with SB (DG: 22.2%), FGB (DG: 14.9%) and WB (DG:
      14.9%). The peak plasma glucose varied between 5.72 +/- 0.67 mmol/l with FGB and
      6.52 +/- 0.64 mmol/l with SFB (treatment p < 0.05). These results confirm the
      post-prandial changes in plasma glucose and insulin after intake of the different
      barley products, but also show that there was no association of the highest
      degree of gelatinization in the different barley diets with the most pronounced
      glycaemic or insulinaemic response.

PMID- 17516951
TI  - Effect of extruding the cereal and/or the legume protein supplement of a compound
      feed on in vitro ruminal nutrient digestion and nitrogen metabolism.
AB  - An experiment was performed to evaluate the effect of extruding the cereal and/or
      the protein supplement of a compound feed for intensively reared calves on
      ruminal N metabolism using an in vitro culture system. A conventional compound
      feed was produced without extruding [treatment non-extruded (NE)], with the
      cereal blend extruded (CE), with the protein blend extruded (PE) and with both
      cereal and protein blends extruded (CPE). Four experimental diets, consisted of
      0.90 of each experimental compound feed and 0.10 barley straw were assessed using
      dual-flow continuous-culture fermenters. (15)N infusion as ammonia sulphate was
      used to label the microbial population. Average NH(3) concentration in fermenter
      effluents ranged from 270 mg/l with diet NE to 69 mg/l for diet CPE (p < 0.05)
      and volatile fatty acid concentrations ranged from 161 mm in diet PE to 130 mm in
      diet CPE (p < 0.05). Diets PE and CPE showed a lower true organic matter
      degradability (49.5% and 48.2%) than NE and CE (52.8% and 52.2%). Non-ammonia
      nitrogen flow in effluents was highest on diet CPE, intermediate on diets CE and
      PE and lowest on diet NE (p < 0.01), reflecting the differences in dietary N flow
      and dietary protein degradability (71.2%, 63.7%, 61.2% and 50.0%, respectively,
      for NE, CE, PE, CPE; p < 0.001). In contrast, microbial protein synthesis
      efficiency was lower for treatments including the cereal blend extruded, although
      the resulted differences were only significant (p < 0.001) for CPE diet.

PMID- 17516952
TI  - Additional data on energy requirements of young adult cats measured by indirect
      calorimetry.
AB  - Measurements of nitrogen, carbon and energy balances were done on eight female
      adult cats aged approximately 1.5 years with the help of respiration chambers.
      The cats were fed with a marked dry food for kittens (Biomill kitten). Faeces and
      urine samples were collected with the help of a special cat toilet that allows
      the single collection of both materials. The calculated energy requirement of
      these eight female cats was 239.6 kJ ME/kg BW/day (R(2) = 0.98). Including the
      data, on 12 young male adult cats, of Lauger, (2001), an energy requirement of
      238 kJ ME/kg BW/day (R(2) = 0.95) could be calculated. From these data, it can be
      followed that the energy requirements of young, active cats are higher than that
      of the older cats. The method of indirect calorimetry does not necessarily lead
      to lower energy requirements.

PMID- 17516953
TI  - Basic data on food intake, nutrient digestibility and energy requirements of
      lorikeets.
AB  - Although knowledge of the nutrient requirements of pet birds has increased a lot
      over the last few years, basic data on food and water intake and the energy
      requirements of nectarivorous species, such as lorikeets, are scarce. Thus, the
      aim of this study was to try to generate some of these data for lorikeets kept at
      maintenance. Determination of the daily maintenance energy requirement enables
      calculation of the daily ration and thus, the appropriate nutrient concentrations
      in order to maintain body weight. Investigations were carried out with six
      Goldie's lorikeets (GL; Trichoglossus goldiei: 40-50 g BW; 1-4 years) and six
      rainbow lorikeets (RL; Trichoglossus haematodus haematodus: 120-140 g BW; 1-12
      years). Three of the most commonly used diets/foods (commercial 'lory
      soup'/apples/pollen: crude ash - 52.9/17.8/18.8; crude protein - 178/32.5/191;
      crude fat - 52.8/0.89/73.1; crude fibre - 17.9/40.5/30.4; starch - 139/not
      detectable/127; sugar - 522/859/418 g/kg DM; ME - 13.9/14.6/10.9 MJ/kg DM) were
      individually offered ad libitum. The measured dry matter (DM) intake (g/100 g BW)
      corresponded well to the values reported for granivorous bird species of similar
      body mass. Both lorikeet species achieved an apparent digestibility of organic
      matter of more than 90% for apples, approximately 82% for 'lory soup' and
      approximately 55% for pollen. The water content of the food affected the DM
      content of the excreta; 8% when fed 'lory soup', 2% for apples and approximately
      30% when fed pollen. Regression analysis of body weight change relative to energy
      intake demonstrated constant body mass (assuming no change in body composition)
      when the daily energy intakes were 860 (GL) or 650 (RL) kJ ME/kg BW(0.75).

PMID- 17516955
TI  - Hysteroscopic sterilisation: is laparoscopic sterilisation a thing of the past?

PMID- 17516956
TI  - Diagnostic hysteroscopy in abnormal uterine bleeding: a systematic review and
      meta-analysis.
AB  - BACKGROUND: This study was conducted to assess the accuracy and feasibility of
      diagnostic hysteroscopy in the evaluation of intrauterine abnormalities in women
      with abnormal uterine bleeding. SEARCH STRATEGY: Electronic databases were
      searched from 1 January 1965 to 1 January 2006 without language selection. The
      medical subject heading (MeSH) and textwords for the following terms were used:
      hysteroscopy, diagnosis, histology, histopathology, hysterectomy, biopsy,
      sensitivity and specificity. SETTING: University Hospital. SELECTION CRITERIA:
      The inclusion criteria were report on accuracy of diagnostic hysteroscopy in
      women with abnormal uterine bleeding compared to histology collected with guided
      biopsy during hysteroscopy, operative hysteroscopy or hysterectomy. DATA
      COLLECTION AND ANALYSIS: Electronic databases were searched for relevant studies
      and references were cross-checked. Validity was assessed and data were extracted
      independently by two authors. Heterogeneity was calculated and data were pooled.
      Subgroup analysis was performed according to validity criteria, study quality,
      menopausal state, time, setting and performance of the procedure. The pooled
      sensitivity, specificity, likelihood ratios, post-test probabilities and
      feasibility of diagnostic hysteroscopy on the prediction of uterine cavity
      abnormalities. Post-test probabilities were derived from the likelihood ratios
      and prevalence of intrauterine abnormalities among included studies. Feasibility
      included technical success rate and complication rate. MAIN RESULTS: One
      population of homogeneous data could be identified, consisting of patients with
      postmenopausal bleeding. In this subgroup the positive and negative likelihood
      ratios were 7.9 (95% CI 4.79-13.10) and 0.04 (95% CI 0.02-0.09), raising the pre
      test probability from 0.61 to a post-test probability of 0.93 (95% CI 0.88-0.95)
      for positive results and reducing it to 0.06 (95% CI 0.03-0.13) for negative
      results. The pooled likelihood ratios of all studies included, calculated with
      the random effects model, were 6.5 (95% CI 4.1-10.4) and 0.08 (95% CI 0.07-0.10),
      changing the pre-test probability of 0.46 to post-test probabilities of 0.85 (95%
      CI 0.78-0.90) and 0.07 (0.06-0.08) for positive and negative results
      respectively. Subgroup analyses gave similar results. The overall success rate of
      diagnostic hysteroscopy was estimated at 96.9% (SD 5.2%, range 83-100%).
      CONCLUSIONS: This systematic review and meta-analysis shows that diagnostic
      hysteroscopy is both accurate and feasible in the diagnosis of intrauterine
      abnormalities.

PMID- 17516957
TI  - The feasibility, success and patient satisfaction associated with outpatient
      hysteroscopic sterilisation.
AB  - OBJECTIVE: To determine the feasibility and patient satisfaction of female
      sterilisation using the Essure system in an outpatient hysteroscopy clinic
      without conscious sedation or general anaesthesia. DESIGN: Prospective cohort
      study. SETTING: Outpatient hysteroscopy clinic in a large teaching hospital.
      POPULATION: Women undergoing outpatient hysteroscopic sterilisation using the
      Essure system for permanent fertility control. METHODS: Demographic and
      procedural data were prospectively collected from 112 consecutive women
      undergoing outpatient hysteroscopic sterilisation without sedation or general
      anaesthesia. A hysterosalpingogram (HSG) was performed routinely in all women 3
      months after the procedure to confirm bilateral tubal occlusion. Postal
      questionnaires were sent at this time enquiring about patient satisfaction and
      experience with the outpatient procedure. Multivariable logistic regression was
      used to identify factors independently predictive of successful completion of the
      procedure. MAIN OUTCOME MEASURES: Technical feasibility, predictive factors for
      technical success (operator, body mass index, uterine size, axis, menstrual phase
      and cervical stenosis), complications, tubal occlusion on HSG, patient
      satisfaction and procedure-related experience. RESULTS: Successful bilateral
      tubal placement of the Essure microinserts was achieved in 103/112 (92%, 95% CI
      85-96%) women. Nonsecretory phase of the menstrual cycle (P = 0.04) and a
      clinically normal-sized uterus (P = 0.003) were independently predictive for
      successful completion of the outpatient procedure on multivariable modelling.
      There were no major procedure-related complications recorded, but transient
      vasovagal reactions occurred in 5/112 (5%) women. Of the original cohort of 112
      women with successful procedures, 84 women were 3 months postprocedure and had
      undergone a HSG. Bilateral tubal occlusion was confirmed in 83/84 (99%, 95% CI 94
      100%) women at 3 months and in 100% at 6 months. Seventy-six of 84 (91%) had
      returned the questionnaires, and 70/73 (96%, 95% CI 88-99%) were satisfied with
      their overall experience of the procedure including radiological follow up, with
      most reporting being 'very satisfied' (64/73, 88%, 95% CI 78-94%). CONCLUSIONS:
      Outpatient hysteroscopic sterilisation using the Essure system without sedation
      or general anaesthesia is a successful and safe procedure associated with high
      rates of patient satisfaction. If practical, women should be scheduled to have
      their procedures in the proliferative phase of the menstrual cycle to optimise
      successful placement of Essure devices, especially if the uterus is clinically
      enlarged.

PMID- 17516958
TI  - A randomised placebo-controlled trial to determine the effect of iron
      supplementation on pregnancy outcome in pregnant women with haemoglobin > or =
      13.2 g/dl.
AB  - OBJECTIVE: To study the effect of iron supplementation on pregnancy outcome in
      pregnant women with haemoglobin (Hb) > or = 13.2 g/dl. DESIGN: A randomised,
      double-blind, placebo-controlled trial. SETTING: Routine health services.
      POPULATION: Seven hundred and twenty-seven pregnant women with Hb > or = 13.2
      g/dl in the early stage of the second trimester. METHODS: Each woman took one
      ferrous sulphate [DOSAGE ERROR CORRECTED] tablet (150 g tablet, containing 50 mg
      of elemental iron) [DOSAGE ERROR CORRECTED] daily in the case group (n = 370) or
      placebo in the control group (n = 357) throughout pregnancy. MAIN OUTCOME
      MEASURES: Pregnancy outcome. RESULTS: While there were no significant differences
      in demographic and obstetric characteristics between the two groups before any
      intervention, small-for-gestational-age birth rate and the number of women with
      hypertension disorder increased significantly in the case group in comparison
      with the control group (57 [15.7%] versus 36 [10.3%], P = 0.035, 10 [2.7%] versus
      3 [8%], P = 0.05, respectively). CONCLUSIONS: Our finding proves that routine
      iron supplementation in nonanaemic women is not rational and may be harmful.

PMID- 17516959
TI  - Severe twin-twin transfusion syndrome: outcome after fetoscopic laser ablation of
      the placental vascular equator.
AB  - OBJECTIVE: To assess the safety and efficacy of a modified fetoscopic laser
      ablation technique for the management of severe twin-twin transfusion syndrome
      (TTTS) in a large series of pregnancies. DESIGN: Prospective cohort study.
      SETTING: Tertiary referral fetal medicine unit. POPULATION: Women with
      pregnancies complicated by severe TTTS (Quintero stage III or IV), before 26
      weeks of gestation. METHODS: Fetoscopic laser ablation of placental anastomoses
      was performed. The sonoendoscopic approach was used to identify the placental
      vascular equator and to photocoagulate crossing vessels. MAIN OUTCOME MEASURES:
      Overall survival, fetal and perinatal mortalities, gestational age at delivery,
      birthweight, operating time and recurrence of TTTS. RESULTS: A total of 77 women
      underwent the procedure. The mean gestational age at treatment was 20 (range 16
      26) weeks. On average, four vessels were ablated during each procedure, with a
      mean operative time of 15 (range 5-25) minutes. None of the women required a
      repeat fetoscopic laser treatment for recurrence of the TTTS. There was at least
      one survivor in 74% (57/77) of pregnancies, and the overall survival rate was 57%
      (88/154). CONCLUSIONS: Fetoscopic laser ablation is a safe and effective form of
      treatment in the management of severe TTTS. The technique of identifying the
      common villous district of the placenta by ultrasound and photocoagulating any
      vessels crossing the vascular equator appears to be an acceptable alternative to
      both the nonselective and highly selective methods described so far. This
      approach is associated with a short operating time, low likelihood of TTTS
      recurrence or fetal anaemia and with survival results that are equivalent to
      previously reported techniques.

PMID- 17516960
TI  - Twin-to-twin transfusion syndrome after 26 weeks of gestation: is there a role
      for fetoscopic laser surgery?
AB  - OBJECTIVE: To compare fetoscopic laser surgery with amniodrainage in the
      treatment of twin-to-twin transfusion syndrome (TTTS) diagnosed after 26 weeks of
      gestation. DESIGN: A retrospective cohort study. SETTING: Leiden University
      Medical Centre, a tertiary referral hospital for fetal therapy. POPULATION:
      Between January 1991 and February 2006, 21 TTTS cases were diagnosed and treated
      after 26 weeks of gestation. METHODS: Treatment of TTTS consisted of either
      amniodrainage or fetoscopic laser coagulation of vascular anastomoses. MAIN
      OUTCOME MEASURES:  PRIMARY OUTCOME: adverse outcome (intrauterine or neonatal
      death, major neonatal morbidity and/or severe cerebral injury). Secondary
      outcome: gestational age at birth. RESULTS: Eleven TTTS cases were treated with
      amniodrainage and ten with laser surgery. Median gestational age at birth in the
      amniodrainage group and in the laser surgery group was 29 and 31 weeks,
      respectively (P = 0.17) All infants were born alive. Major neonatal morbidity
      occurred more often in the amniodrainage group than in the laser surgery group,
      27% (6/22) and 0% (0/20), respectively (P = 0.02). Severe cerebral injury in the
      amniodrainage group and in the laser surgery group occurred in 23% (5/22) and 15%
      (3/20) of infants, respectively (P = 0.70). Neonatal mortality in the
      amniodrainage group and in the laser surgery group was 14% (3/22) and 0% (0/20),
      respectively (P = 0.23). Overall adverse outcome was 36% (8/22) in the
      amniodrainage group and 15% (3/20) in the laser surgery group (P = 0.17).
      CONCLUSION: In TTTS diagnosed after 26 weeks of gestation, amniodrainage and
      laser surgery both result in 100% survival. However, infants born after laser
      surgery have less major neonatal morbidity.

PMID- 17516961
TI  - The influence of maternal smoking habits on the risk of subsequent stillbirth: is
      there a causal relation?
AB  - OBJECTIVE: Maternal smoking has previously been associated with risk of
      stillbirth. If women who quit smoking reduce their risk of stillbirth, the
      hypothesis of a causal association would be supported. DESIGN: Prospective cohort
      study. SETTING: Nationwide study in Sweden. POPULATION: All primiparous women who
      delivered their first and second consecutive single births between 1983 and 2001,
      giving a total number of 526,691 women. METHOD: A population-based Swedish study
      with data from the Medical Birth Registry, the Immigration Registry and the
      Education Registry. Logistic regression analyses were used to estimate odds
      ratios, using 95% confidence intervals. MAIN OUTCOME MEASURE: Stillbirth in the
      second pregnancy. RESULTS: Compared with nonsmokers in both pregnancies, women
      who smoked during the first pregnancy but not during the second do not have an
      increased risk of stillbirth (OR 1.02; 95% CI 0.79-1.30), while corresponding
      risk among women who smoked during both pregnancies was 1.35 (95% CI 1.15-1.58).
      CONCLUSION: The result supports that maternal smoking during pregnancy is
      causally associated with stillbirth risk. Smoking is a preventable cause of
      stillbirth, and smoking interventions is an important issue in antenatal care.

PMID- 17516962
TI  - Maternal and biochemical predictors of antepartum stillbirth among nulliparous
      women in relation to gestational age of fetal death.
AB  - OBJECTIVE: To determine whether maternal serum levels of alphafetoprotein (alpha
      FP) and human chorionic gonadotrophin (hCG) at 15-21 weeks provided clinically
      useful prediction of stillbirth in first pregnancies. DESIGN: Retrospective study
      of record linkage of a regional serum screening laboratory to national registries
      of pregnancy outcome and perinatal death. SETTING: West of Scotland, 1992-2001.
      POPULATION: A total of 84,769 eligible primigravid women delivering an infant at
      or beyond 24 weeks of gestation. METHODS: The risk of stillbirth between 24 and
      43 weeks was assessed using the Cox proportional hazards model. Logistic
      regression models within gestational windows were then used to estimate predicted
      probability. Screening performance was assessed as area under the receiver
      operating characteristic (ROC) curve. MAIN OUTCOME MEASURE: Antepartum stillbirth
      unrelated to congenital abnormality. RESULTS: The odds ratio (95% CI) for
      stillbirth at 24-28 weeks for women in the top 1% were 11.97 (5.34-26.83) for
      alpha-FP and 5.80 (2.19-15.40) for hCG. The corresponding odds ratios for
      stillbirth at or after 37 weeks were 2.44 (0.74-8.10) and 0.79 (0.11-5.86),
      respectively. Adding biochemical to maternal data increased the area under the
      ROC curve from 0.66 to 0.75 for stillbirth between 24 and 28 weeks but only
      increased it from 0.64 to 0.65 for stillbirth at term and post-term. Women in the
      top 5% of predicted risk had a positive likelihood ratio of 7.8 at 24-28 weeks,
      3.7 at 29-32 weeks, 5.1 at 33-36 weeks and 3.4 at 37-43 weeks, and the
      corresponding positive predictive values were 0.97, 0.33, 0.47 and 0.63%,
      respectively. CONCLUSIONS: Maternal serum levels of alpha-FP and hCG were
      statistically associated with stillbirth risk. However, the predictive ability
      was generally poor except for losses at extreme preterm gestations, where
      prevention may be difficult and interventions have the potential to cause
      significant harm.

PMID- 17516963
TI  - Placenta weight percentile curves for singleton deliveries.
AB  - OBJECTIVE: To produce population-based, gender- and gestational-age-specific
      centile curves for placental weight. DESIGN: Population study. SETTING: Medical
      Birth Registry of Norway. POPULATION: All singleton live births in Norway from 1
      January 1999 to 31 December 2002. METHODS: In a cohort of children born in
      Norway, placental weights and the ratio of the birthweight to the placental
      weight were analysed to produce percentile curves. MAIN OUTCOME MEASURES:
      Placental weight, birthweight-to-placental weight ratio. RESULTS: Tables and
      figures are presented for placental percentiles curves according to gestational
      age and gender. Also, tables and figures are presented for the ratio of
      birthweight to placental weight. CONCLUSIONS To our knowledge, this is the first
      time that population percentile curves have been produced for placental weights
      and hence for the ratio of birthweight to placental weight. These percentile
      curves may act as a reference for other populations as well until population
      specific curves can be produced.

PMID- 17516965
TI  - Spontaneous preterm birth of liveborn infants in women at low risk in Australia
      over 10 years: a population-based study.
AB  - OBJECTIVES: To describe a 10-year trend in preterm birth. DESIGN: Population
      based study. SETTING: Australia. POPULATION: All women who gave birth during 1994
      03. METHODS: The proportion of spontaneous preterm births (greater than or equal
      to 22 weeks of gestation and less than 37 completed weeks of gestation) was
      calculated by dividing the number of women who had a live spontaneous preterm
      birth (excluding elective caesarean section and induction of labour) by the total
      number of women who had a live birth after spontaneous onset of labour (excluding
      elective caesarean section and induction of labour). This method was repeated for
      the selected population of women at low risk. MAIN OUTCOME MEASURE: Preterm birth
      rates among the overall population of women; preterm birth among all women with a
      spontaneous onset of labour; and preterm birth in a selected population of women
      who were either primiparous or multiparous, non-Indigenous; aged 20-40 years and
      who gave birth to a live singleton baby after the spontaneous onset of labour.
      RESULTS: Over the 10-year study period, the proportion of all women having a live
      preterm birth in Australia increased by 12.1% (from 5.9% in 1994 to 6.6% in
      2003). Among women with a spontaneous onset of labour, there was an increase of
      18.3% (from 5.7 to 6.7%). Among the selected population of low-risk women after
      the spontaneous onset of labour, the rate increased by 10.7% (from 5.6 to 6.2%)
      among first time mothers and by 19.2% (4.4-5.2%) among selected multiparous
      women. CONCLUSIONS: Over the 10-year period of 1994-03, the rate of spontaneous
      preterm birth among low-risk women having a live singleton birth has risen in
      Australia.

PMID- 17516964
TI  - Number of children and coronary heart disease risk factors in men and women from
      a British birth cohort.
AB  - OBJECTIVE: To examine the association between number of children and coronary
      heart disease (CHD) risk factors in women and men. DESIGN: Prospective cohort
      study. SETTING: Britain. SAMPLE: A total of 2977 individuals (51% women) from the
      Medical Research Council National Survey of Health and Development, a birth
      cohort study of individuals born in Britain in 1946 and followed up regularly
      throughout life. MAIN OUTCOME MEASURES: Blood pressure, body mass index (BMI),
      waist to hip ratio (WHR), total, high-density lipoprotein and low-density
      lipoprotein cholesterol and triglyceride levels, and glycated haemoglobin (HbA1C)
      measured at age of 53 years. RESULTS: Number of children showed no consistent
      relationship with CHD risk factors at age 53 years in either men or women, and no
      obvious and consistent sex differences were observed. Mean BMI (95% CI) increased
      with increasing numbers of children (P = 0.01) in women from 27.4 kg/m2 (26.6
      28.2) in those with one child to 28.6 kg/m2 (27.6-29.6) in those with four or
      more children. WHR and type II diabetes in women and HbA1C in men were the only
      other risk factors exhibiting a linearly increasing trend with increasing number
      of children. These associations were largely explained by adjustment for
      behavioural and lifestyle variables. CONCLUSION: Our findings suggest that any
      association between number of children and CHD risk factors is a result of
      lifestyle and behaviours associated with family life rather than being as result
      of the biological impact of pregnancy in women.

PMID- 17516966
TI  - Randomised clinical trial of a laxative alone versus a laxative and a bulking
      agent after primary repair of obstetric anal sphincter injury.
AB  - OBJECTIVE: To compare two postpartum laxative regimens in women who have
      undergone primary repair of obstetric anal sphincter injury. DESIGN: Randomised
      controlled trial. SETTING: National Maternity Hospital, Dublin. POPULATION: A
      total of 147 postpartum women who had sustained anal sphincter injury at vaginal
      birth. METHODS: Women were randomised to receive either lactulose alone thrice
      daily for the first three postpartum days followed by sufficient lactulose to
      maintain a soft stool over the following 10 days (lactulose group, n = 77) or the
      lactulose regimen combined with a sachet of ispaghula husk daily for the first 10
      postpartum days (Fybogel group, n = 70). All patients kept a diary of bowel habit
      for the first 10 postpartum days and were invited to return for review at 3
      months postpartum. MAIN OUTCOME MEASURES: Patient discomfort with first
      postpartum bowel motion, incidence of postnatal constipation and incontinence and
      incontinence score in postnatal period. RESULTS: Pain scores were similar in the
      two treatment groups; but incontinence in the immediate postnatal period was more
      frequent with the two preparations compared with lactulose alone (32.86% versus
      18.18%, P = 0.03). CONCLUSIONS: This study does not support routine prescribing
      of a stool-bulking agent in addition to a laxative in the immediate postnatal
      period for women who have sustained anal sphincter injury at vaginal delivery.

PMID- 17516967
TI  - Dynamics and incidence patterns of maternal complications in early-onset
      hypertension of pregnancy.
AB  - OBJECTIVE: To describe the variable disease expression and the patterns of
      development of major maternal morbidity and HELLP (haemolysis, elevated liver
      enzymes and low platelet count) syndrome in women with different subtypes of
      hypertensive disorders of pregnancy. DESIGN: Prospective cohort study. SETTING:
      Two university hospitals, tertiary care centres. POPULATION: Two hundred and
      sixteen women participating in a randomised trial of temporising management in
      early-onset hypertensive disease (PETRA trial). Women were between 24 and 34
      completed weeks and had either HELLP syndrome, severe pre-eclampsia, eclampsia or
      hypertension and fetal growth restriction. Women were delivered in the event of
      fetal marked heart rate abnormalities, pulmonary oedema, therapy-resistant
      hypertension or recurrent HELLP syndrome. METHODS: Trial data were reanalysed to
      assess the time of onset of major maternal morbidity (e.g. pulmonary oedema,
      liver haematoma), HELLP syndrome and clinical disease. Associations between
      clinical parameters and prolongation of pregnancy were explored using logistic
      regression. MAIN OUTCOME MEASURES: Diagnosis from admittance to discharge, major
      maternal morbidity and prolongation of pregnancy. RESULTS: The median time to
      delivery or fetal death was 8.2 (range 0.1-44) days. At study entry, 56 women
      (26%) had more than one diagnosis; this increased to 171 women (79%) by the time
      of discharge. The incidence of major maternal morbidity (total 26) was 4.2% at 2
      4 days after inclusion and a mean of 1.7% (range 0-2%) thereafter per time frame
      of 3 days. The mean incidence of new or recurrent HELLP syndrome episodes was
      5.5% (range 1.9-8.7%) per time frame of 3 days during the first 3 weeks after
      inclusion. CONCLUSIONS: Pre-eclampsia is a dynamic disease, with extensive
      overlap of subtypes of the syndrome. Prolongation of pregnancy in early-onset
      hypertensive disorders results in the development of further HELLP syndrome
      episodes and reversible major maternal morbidity but may improve perinatal
      healthy survival.

PMID- 17516968
TI  - Investigation of an increase in postpartum haemorrhage in Canada.
AB  - OBJECTIVE: To investigate the cause of a recent increase in hysterectomies for
      postpartum haemorrhage in Canada. DESIGN: Retrospective cohort study. SETTING:
      Canada between 1991 and 2004. POPULATION: All hospital deliveries in Canada as
      documented in the database of the Canadian Institute for Health Information
      (excluding incomplete data from Quebec, Manitoba and Nova Scotia). METHODS:
      Deliveries with postpartum haemorrhage by subtype were identified using
      International Classification of Diseases codes, while hysterectomies were
      identified using procedure codes. Changes in determinants of postpartum
      haemorrhage (all postpartum haemorrhage and that requiring hysterectomy) were
      examined, and crude and adjusted period changes were assessed using logistic
      models. MAIN OUTCOME MEASURES: Postpartum haemorrhage, postpartum haemorrhage
      with hysterectomy, postpartum haemorrhage with blood transfusion and postpartum
      haemorrhage by subtype. RESULTS: Rates of postpartum haemorrhage increased from
      4.1% in 1991 to 5.1% in 2004 (23% increase, 95% CI 20-26%), while rates of
      postpartum haemorrhage with hysterectomy increased from 24.0 in 1991 to 41.7 per
      100,000 deliveries in 2004 (73% increase, 95% CI 27-137%). These increases were
      because of an increase in atonic postpartum haemorrhage, from 29.4 per 1000
      deliveries in 1991 to 39.5 per 1000 deliveries in 2004 (34% increase, 95% CI 31
      38%). Adjustment for temporal changes in risk factors did not explain the
      increase in atonic postpartum haemorrhage but attenuated the increase in atonic
      postpartum haemorrhage with hysterectomy. CONCLUSIONS: There has been a recent,
      unexplained increase in the frequency, and possibly the severity, of atonic
      postpartum haemorrhage in Canada.

PMID- 17516969
TI  - Shortened duration of human chorionic gonadotrophin surveillance following
      complete or partial hydatidiform mole: evidence for revised protocol of a UK
      regional trophoblastic disease unit.
AB  - Following hydatidiform mole, women are at increased risk of persistent
      gestational trophoblastic neoplasia (pGTN) and are therefore monitored using
      serum human chorionic gonadotrophin (hCG) concentration measurements. We
      retrospectively evaluated the policy of extended (2 year) follow up for women
      with hCG concentrations returning to normal >56 days after evacuation. Of 6701
      women registered for hCG follow up, 422 (6%) developed pGTN, 412 (98%) of these
      women presented within 6 months after evacuation. Three developed pGTN at 402,
      677 and 1267 days after evacuation following spontaneous normalisation of hCG
      levels. Only one woman was detected by routine extended follow up. Prolonged
      surveillance after molar pregnancy causes significant anxiety and is not cost
      effective. Therefore, the current revised protocol comprises hCG follow up for 6
      months after spontaneous return of hCG levels to normal for all women.

PMID- 17516970
TI  - Success rate and patient satisfaction with the Essure sterilisation in an
      outpatient setting: a prospective study of 857 women.
AB  - After 857 women with Essure system inserted for tubal obstruction as a method of
      sterilization in an outpatient setting, insertion is achieved in close to 99% of
      the women. Physician described the procedure as very difficult in 15% of the
      cases, mainly due to anatomical tubal anomalis or tubal spasm, and women felt
      highly satisfied in all cases.

PMID- 17516971
TI  - Comparison of self-administered vaginal misoprostol versus placebo for cervical
      ripening prior to operative hysteroscopy using a sequential trial design.
AB  - OBJECTIVE: To compare the impact of 1000-microgram self-administered vaginal
      misoprostol versus self-administered vaginal placebo at home on preoperative
      cervical ripening in both premenopausal and postmenopausal women prior to
      outpatient resectoscopy. DESIGN: Randomised, double-blind, placebo-controlled
      sequential trial. SETTING: Norwegian university teaching hospital. SAMPLE:
      Premenopausal and postmenopausal women referred to outpatient resectoscopy.
      METHODS: The women were randomised to either 1000 micrograms of self-administered
      vaginal misoprostol or self-administered vaginal placebo the evening before
      outpatient resectoscopy. MAIN OUTCOME MEASURES: Preoperative cervical dilatation,
      acceptability and complications. RESULTS: (a) Intraoperative findings and
      distribution of cervical dilatation in the two treatment groups. Values are given
      as median (range) or n (%). (b) Acceptability in the two treatment groups. Values
      are given as completely acceptable, n (%); fairly acceptable, n (%); fairly
      unacceptable, n (%) and completely unacceptable, n (%). (c) Pain in the two
      treatment groups. Pain was measured with a visual analogue scale score, scale
      ranges from 0 (no pain) to 10 (unbearable pain). Values are given as median
      (range). (d) Occurrence of adverse effects in the two treatment groups. Values
      are given as n (%). (e) Complications, given as n (%).

PMID- 17516972
TI  - The Control of Hypertension In Pregnancy Study pilot trial.
AB  - OBJECTIVE: To determine whether 'less tight' (versus 'tight') control of
      nonsevere hypertension results in a difference in diastolic blood pressure (dBP)
      between groups. DESIGN: Randomised controlled trial (ISRCTN#57277508). SETTING:
      Seventeen obstetric centres in Canada, Australia, New Zealand, and UK.
      POPULATION: Inclusion: pregnant women, dBP 90-109 mmHg, pre-existing/gestational
      hypertension; live fetus(es); and 20-33(+6) weeks. Exclusion: systolic blood
      pressure > or = 170 mmHg and proteinuria, contraindication, or major fetal
      anomaly. METHODS: Randomisation to less tight (target dBP, 100 mmHg) or tight
      (target dBP, 85 mmHg) blood pressure control. MAIN OUTCOME MEASURES: Primary:
      mean dBP at 28, 32 and 36 weeks. Secondary: clinician compliance and women's
      satisfaction. Other: serious perinatal and maternal complications. RESULTS: A
      total of 132 women were randomised to less tight (n = 66; seven had no study
      visit) or tight control (n= 66; one was lost to follow up; seven had no study
      visit). Mean dBP was significantly lower with tight control: -3.5 mmHg, 95%
      credible interval (-6.4, -0.6). Clinician compliance was 79% in both groups.
      Women were satisfied with their care. With less tight (versus tight) control, the
      rates of other treatments and outcomes were the following: post-randomisation
      antenatal antihypertensive medication use: 46 (69.7%) versus 58 (89.2%), severe
      hypertension: 38 (57.6%) versus 26 (40.0%), proteinuria: 16 (24.2%) versus 20
      (30.8%), serious maternal complications: 3 (4.6%) versus 2 (3.1%), preterm birth:
      24 (36.4%) versus 26 (40.0%), birthweight: 2675 +/- 858 versus 2501 +/- 855 g,
      neonatal intensive care unit (NICU) admission: 15 (22.7%) versus 22 (34.4%), and
      serious perinatal complications: 9 (13.6%) versus 14 (21.5%). CONCLUSION: The
      CHIPS pilot trial confirms the feasibility and importance of a large definitive
      trial to determine the effects of less tight control on serious perinatal and
      maternal complications.

PMID- 17516973
TI  - Nigerian politics and safe motherhood.

PMID- 17516975
TI  - Precancerous changes in the cervix and risk of subsequent preterm birth.

PMID- 17516977
TI  - Precancerous changes in the cervix and risk of subsequent preterm birth.

PMID- 17516979
TI  - Have we dismissed ablative treatment too soon in colposcopy practice?

PMID- 17516980
TI  - Low levels of prenatal alcohol exposure can cause fetal damage.

PMID- 17516983
TI  - Maternal pseudoprimary hyperaldosteronism in twin-twin transfusion syndrome and
      its correction with treatment.

PMID- 17516984
TI  - Pregnancy-induced hypertension and infant mortality.

PMID- 17516985
TI  - Risk of chikungunya or dengue infections in pregnant women.

PMID- 17516987
TI  - On the mechanism of coronary vasodilation induced by angiotensin-(1-7) in the
      isolated guinea pig heart.
AB  - Various mechanisms have been postulated to be involved in angiotensin-(1-7)
      induced endothelium-dependent vasodilation. Here, we characterized the
      vasodilator action of angiotensin-(1-7) in the isolated guinea pig heart.
      Angiotensin-(1-7) (1-10 nmol, bolus) induced dose-dependent increase in the
      coronary flow. The coronary vasodilation induced by angiotensin-(1-7) was
      significantly reduced by the nitric oxide synthase inhibitor, L-N(G)
      nitroarginine methyl ester (L-NAME) (100 microM) and abolished by a B(2) receptor
      antagonist, icatibant (100 nM). Coronary vasodilation induced by bradykinin (3
      pmol, bolus) was inhibited by L-NAME and icatibant to similar extent as that
      induced by angiotensin-(1-7). Neither the selective AT(2) angiotensin receptor
      antagonist, PD123319 (1 microM), nor the antagonist of a putative angiotensin-(1
      7) receptors, [D-alanine-7]-angiotensin-(1-7) (A-779, 1 microM), influenced the
      response to angiotensin-(1-7). In conclusion, in the isolated guinea pig heart
      angiotensin-(1-7) induces coronary vasodilation that is mediated by endogenous
      bradykinin and subsequent stimulation of nitric oxide release through endothelial
      B(2) receptors. In contrast to other vascular beds, AT(2) angiotensin receptors
      and specific angiotensin-(1-7) receptors do not appear involved in angiotensin-(1
      7)-induced coronary vasodilation in the isolated guinea pig heart.

PMID- 17516988
TI  - Delayed protection of tetramethylpyrazine on neonatal rat cardiomyocytes
      subjected to anoxia-reoxygenation injury.
AB  - The aim of this study was to investigate the cardioprotective effects and the
      possible mechanisms of delayed preconditioning induced by tetramethylpyrazine
      (TMP) in cultured neonatal rat cardiomyocytes subjected to anoxia-reoxygenation
      injury. Cultured neonatal rat cardiomyocytes were preconditioned using TMP at
      different concentrations (100, 200 and 500 microM). Cell viability, lactate
      dehydrogenase release, malondialdehyde formation, superoxide dismutase activity
      and glutathione peroxidase activity were measured to determine the protective
      effects against anoxia-reoxygenation injury. The expression of heat shock protein
      70 (Hsp70) was measured 24 hr after TMP preconditioning by Western blot analysis.
      The results showed that TMP decreased lactate dehydrogenase release, increased
      cell viability, suppressed malondialdehyde formation and augmented activities of
      superoxide dismutase and glutathione peroxidase in a concentration-dependent
      manner. Moreover, the delayed protection was abolished by pre-treating with
      either protein kinase C inhibitor chelerythrine chloride or PD98059, a selective
      inhibitor of extracellular signal-regulated protein kinase 1/2, respectively, and
      the expression of Hsp70 was significantly increased in 24 hr after TMP
      preconditioning that was also suppressed by chelerythrine chloride or PD98059.
      These results suggest that TMP can induce delayed cardioprotective effects by
      activation of protein kinase C and extracellular signal-regulated protein kinase
      1/2 signalling pathways and subsequent increased expression of Hsp70 in rat
      neonatal cardiomyocytes.

PMID- 17516989
TI  - Lycopene, a carotenoid, attenuates cyclosporine-induced renal dysfunction and
      oxidative stress in rats.
AB  - The aim of this study was to investigate the possible protective role of
      antioxidant treatment with lycopene on cyclosporine A-induced nephrotoxicity
      using biochemical and histopatological approaches. Adult male Sprague-Dawley rats
      were randomly divided into four groups. The control group received physiological
      saline; animals in the lycopene group received only lycopene (10 mg/kg); animals
      in the cyclosporine A group received only cyclosporine A (15 mg/kg) and animals
      in cyclosporine plus lycopene group received cyclosporine and lycopene for 21
      days. The effects of lycopene on cyclosporine A-induced nephrotoxicity were
      evaluated by plasma creatinine, urea, sodium and calcium concentrations; kidney
      tissue thiobarbituric acid reactive species, reduced glutathione (GSH),
      glutathione peroxidase (GSH-Px) and catalase activities and histopatological
      examinations. Administration of cyclosporine A to rats induced a marked renal
      failure, characterized with a significant increase in plasma creatinine and urea
      concentrations. Cyclosporine A also induced oxidative stress as indicated by
      increased kidney tissue concentrations of thiobarbituric acid reactive species
      and GSH, and reduced activities of GSH-Px and catalase. Moreover, the kidneys of
      cyclosporine A-treated rats showed tubular necrosis, degeneration, dilatation,
      thickened basement membranes, luminal cast formation and inter-tubular fibrosis.
      Lycopene markedly reduced elevated plasma creatinine, urea levels and
      counteracted the deleterious effects of cyclosporine A on oxidative stress
      markers. In addition, lycopene ameliorated cyclosporine A-induced pathological
      changes including tubular necrosis, degeneration, thickened basement membranes
      and inter-tubular fibrosis when compared to the alone cyclosporine A group. These
      data indicate that the natural antioxidant lycopene might have protective effect
      against cyclosporine-induced nephrotoxicity and oxidative stress in rat.

PMID- 17516990
TI  - Effects of topiramate on mouse eccrine sweat gland responsiveness to heat
      exposure.
AB  - Young mice (2 weeks old) were given topiramate daily for 1 month, and sudomotor
      function was evaluated utilizing impression mould techniques to determine the
      number of sweat glands reactive to heat exposure and sweat output per gland on
      the plantar surface of mice hind-paws. Immunohistochemical quantitation of
      protein gene product 9.5, choline acetyltransferase and tyrosine hydroxylase in
      footpads was determined after topiramate treatment. While a 25% decrease in the
      number of secreting sweat glands and a 42% decline in sweat output per gland were
      observed following topiramate treatment, no significant differences were noted in
      sudomotor innervation, expressed as length of choline acetyltransferase, tyrosine
      hydroxylase and protein gene product 9.5 immunoreactive nerve profiles in single
      secretory coils or in sweat gland sizes within the secretory coil area. Long-term
      topiramate stimulation resulted in a reduction in the number of reactive sweat
      glands, without changes in sweat gland innervation, suggesting that the
      diminished responsiveness of the glands to heat exposure induced by topiramate
      might have resulted from a decrease in the intrinsic regulatory activity of sweat
      glands, as opposed to the loss of periglandular neurotransmitters or the
      impairment of the structure of the glands.

PMID- 17516991
TI  - Inhibitory effect of valproic acid on cytochrome P450 2C9 activity in epilepsy
      patients.
AB  - Drug interactions constitute a major problem in the treatment of epilepsy because
      drug combinations are so common. Valproic acid is a widely used anticonvulsant
      drug with a broad therapeutic spectrum. Case reports suggest interaction between
      valproic acid and other drugs metabolized mainly by cytochrome P450 isoforms. The
      aim of this study was to evaluate the inhibitory effect of valproic acid on
      cytochrome P450 2C9 (CYP2C9) activity by using losartan oxidation as a probe in
      epilepsy patients. Patients were prescribed sodium valproate (mean 200 mg/day for
      the first week and 400 mg/day in the following period) according to their
      clinical need. A single oral dose of 25 mg losartan was given to patients before
      and after the first dose, first week and 4 weeks of valproic acid treatment.
      Losartan and E3174, the CYP2C9-derived carboxylic acid metabolite of losartan in
      8 hr urine were assayed by using high pressure liquid chromatography. Urinary
      losartan/E3174 ratio did not change significantly on the first day (0.9, 0.3-3.5;
      median, range), and first week (0.6, 0.2-3.8; median, range), while a significant
      increase was observed after 4 weeks of valproic acid treatment (1.1, 0.3-5.7;
      median, range) as compared to that of measured before valproic acid
      administration (0.6, 0.1-2.1; median, range) (P = 0.039). The degree of
      inhibition was correlated with the steady-state plasma concentrations of valproic
      acid (r(2) = 0.70, P = 0.04). The results suggest an inhibitory effect of
      valproic acid on CYP2C9 enzyme activity in epilepsy patients at steady state. The
      risk of pharmacokinetic drug-drug interactions should be taken into account
      during concomitant use of valproic acid and CYP2C9 substrates.

PMID- 17516992
TI  - Serum cytokine levels of interleukin-1beta, -6, -8, tumour necrosis factor-alpha
      and vascular endothelial growth factor in breast cancer patients treated with
      tamoxifen and supplemented with co-enzyme Q(10), riboflavin and niacin.
AB  - The prognostic significance of supplementing co-enzyme Q(10) (CoQ(10)),
      riboflavin and niacin (CoRN) along with tamoxifen to breast cancer patients was
      evaluated by measuring the serum cytokine levels of interleukin (IL)-1beta, IL-6,
      IL-8, tumour necrosis factor alpha (TNF-alpha) and vascular endothelial growth
      factor. In the present study, 84 breast cancer patients were randomized to
      receive a daily supplement of CoQ(10) 100 mg, riboflavin 10 mg and niacin 50 mg,
      one dosage per day along with tamoxifen 10 mg twice a day. Serum cytokine levels
      were elevated in untreated breast cancer patients (Group II) and significantly
      reduced after tamoxifen therapy for more than 1 year (Group III). When group III
      breast cancer patients were supplemented with CoRN for 45 days (Group IV) and 90
      days (Group V) along with tamoxifen, a significant reduction in cytokine levels
      were observed (P < 0.05). Such a decrease in serum cytokine levels after CoRN
      supplementation in breast cancer patients may suggest good prognosis and efficacy
      of the treatment, and might even offer protection from metastases and recurrence
      of cancer.

PMID- 17516993
TI  - Compared effect of immunosuppressive drugs cyclosporine A and rapamycin on
      cholesterol homeostasis key enzymes CYP27A1 and HMG-CoA reductase.
AB  - Hyperlipidaemia, i.e. increase in total cholesterol and triglycerides, is a
      common side-effect of the immunosuppressive drugs rapamycin (RAPA) and
      cyclosporine A (CsA), and is probably related to inhibition of the 27
      hydroxylation of cholesterol (acid pathway of bile acid biosynthesis). This might
      be one of the causes for the increase in plasma cholesterol, as 27
      hydroxycholesterol is a potent suppressor of 3-hydroxy-3-methyl-glutaryl-CoA
      reductase (HMGR), a key enzyme of cholesterol synthesis. As the sterol 27
      hydroxylase (CYP27A1) inhibition by CsA is well known, we evaluated the effect of
      another immunosuppressive drug, RAPA, on this enzyme in HepG2 mitochondria, which
      confirmed the dose-dependent inhibition of mitochondrial CYP27A1 by cyclosporine
      (10-20 microM), while the inhibition by RAPA required a higher dose (50-100
      microM). Corresponding K(i) was 10 microM for CsA (non-competitive inhibition)
      and 110 microM for RAPA (competitive inhibition). Cotreatment with both
      immunosuppressive drugs showed an additive inhibitory effect on CYP27A1 activity.
      Later, we analysed the effect of these immunosuppressants on HMGR expression in
      HepG2 cells, and a dose-dependent up-regulation of HMGR gene expression was
      observed. The results suggest that RAPA and CsA are both inhibitors of CYP27A1
      activity with slightly different mechanisms and that they may accordingly
      increase HMGR expression.

PMID- 17516994
TI  - Effect of lycopene on nephrotoxicity induced by mercuric chloride in rats.
AB  - Oxidative stress is an important molecular mechanism for kidney injury in mercury
      poisoning. We studied lycopene, a potent carotenoid found in tomatoes due to its
      large antioxidant properties, and also evaluated the ability of lycopene to
      prevent HgCl(2) nephrotoxicity. Rats were injected with HgCl(2) (0 or 5 mg/kg
      body weight, subcutaneously) 6 hr after lycopene administration (0, 10, 25 or 50
      mg/kg by gavage) and were killed 12 hr after HgCl(2) exposure. HgCl(2)-induced
      inhibition of delta-aminolevulinate dehydratase activity (approximately 35%) and
      increase of lipid peroxidation in kidney (approximately 37%) were prevented by
      lycopene. However, lycopene did not prevent the increase of plasma creatinine
      levels (approximately 123%) and renal tubular necrosis induced by HgCl(2).
      Glutathione peroxidase and catalase activities were enhanced (approximately 71%
      and approximately 41%), while superoxide dismutase activity was depressed
      (approximately 44%) in HgCl(2)-treated rats when compared to control and these
      effects were prevented by lycopene. Our results indicate that although lycopene
      did not prevent HgCl(2)-induced renal failure, it could play a beneficial role
      against HgCl(2) toxicity by preventing lipid peroxidation and changes in the
      activity of delta-aminolevulinate dehydratase and antioxidant enzymes.

PMID- 17516995
TI  - Irinotecan toxicity to human blood cells in vitro: relationship between various
      biomarkers.
AB  - Toxic effects of the antineoplastic drug irinotecan on human blood cells at
      concentrations of 9.0 microg/ml and 4.6 microg/ml were evaluated in vitro. Using
      the alkaline and neutral comet assay significantly increased levels of primary
      DNA damage in lymphocytes were detected. The induction of apoptosis/necrosis, as
      determined by a fluorescent assay, was also notably increased. Cytogenetic
      outcomes of the treatment were assessed by the analysis of structural chromosome
      aberrations and fluorescence in situ hybridization. A significantly higher
      incidence of chromatid breaks and complex quadriradials was observed. Painted
      chromosomes 1, 2 and 4 were equally involved in translocations, but only the
      chromosome 1 was involved in the formation of quadriradials. Sister chromatid
      exchange analysis was performed in parallel with the analysis of lymphocyte
      proliferation kinetics. The higher concentration of irinotecan caused almost
      seven-time increase, while the lower one caused a five-time increase of the basal
      sister chromatid exchange frequency, accompanied with significant lowering of the
      lymphocyte proliferation index. Using the cytokinesis-block micronucleus assay, a
      dose-dependent increase in micronucleus frequency along with the formation of
      nuclear buds and nucleoplasmic bridges was noticed. Inhibitory effects of
      irinotecan on enzyme acetylcholinesterase (AChE) were studied in erythrocytes. An
      IC(50) value of 5.0 x 10(-7) was established. Irinotecan was found to be strong
      inhibitor of the acetylcholine hydrolysis and to cause a continuous decrease of
      catalytic activity of AChE. The results obtained on a single donor may contribute
      to the understanding of irinotecan toxicity, but further in vitro and in vivo
      studies are essential in order to clarify remaining issues, especially on
      possible inter-individual variability in genotoxic responses to the drug.

PMID- 17516996
TI  - Silymarin protection against major reactive oxygen species released by
      environmental toxins: exogenous H2O2 exposure in erythrocytes.
AB  - Silymarin is a polyphenolic plant flavonoid (a mixture of flavonoid isomers such
      as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin
      marianum that has anti-inflammatory, hepatoprotective and anticarcinogenic
      effects. Our earlier studies have shown that silymarin plays a protective role
      against the oxidative damage induced by environmental contaminants like
      benzo(a)pyrene in erythrocyte haemolysates. During the detoxification of these
      environmental contaminants, the major reactive oxygen species generated is
      hydrogen peroxide (H(2)O(2)). Because H(2)O(2 )can easily penetrate into the cell
      and cause damage to biomolecules, the protective role of silymarin was further
      assessed against this cytotoxic agent in vitro in erythrocyte haemolysates. The
      protective effect was monitored by assessing the levels of the antioxidant
      enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione
      reductase, glutathione-s-transferase, glutathione peroxidase and malondialdehyde
      (LPO) in three groups: vehicle control, H(2)O(2)-exposed groups and drug co
      incubation group (H(2)O(2) + silymarin). The protective effect of silymarin on
      the non-enzymic antioxidant glutathione and haemolysis, methaemoglobin content
      and protein carbonyl content were also assessed. It was observed that the
      activities of antioxidant enzymes and glutathione were reduced and the
      malondialdehyde levels were elevated after H(2)O(2 )exposure. There were also
      alterations in haemolysis, methaemoglobin content and protein carbonyl content,
      whereas after the administration of silymarin, the antioxidant enzyme activities
      reversed to near normal with reduced malondialdehyde content and normalized
      haemolysis, methaemoglobin content and protein carbonyl content. The results
      suggest that silymarin possesses substantial protective effect and free radical
      scavenging mechanism against exogenous H(2)O(2)-induced oxidative stress damages,
      hence, can be used as a protective drug against toxicity induced by environmental
      contaminants.

PMID- 17516997
TI  - A new look at infant pointing.
AB  - The current article proposes a new theory of infant pointing involving multiple
      layers of intentionality and shared intentionality. In the context of this
      theory, evidence is presented for a rich interpretation of prelinguistic
      communication, that is, one that posits that when 12-month-old infants point for
      an adult they are in some sense trying to influence her mental states. Moreover,
      evidence is also presented for a deeply social view in which infant pointing is
      best understood--on many levels and in many ways--as depending on uniquely human
      skills and motivations for cooperation and shared intentionality (e.g., joint
      intentions and attention with others). Children's early linguistic skills are
      built on this already existing platform of prelinguistic communication.

PMID- 17516998
TI  - Do infants need social cognition to act socially? An alternative look at infant
      pointing.
AB  - Tomasello, Carpenter, and Liszkowski (2007) present a comprehensive review of the
      infant pointing literature. They conclude that infant pointing demonstrates
      communicative intent from its onset, at about 1 year of age. In this commentary,
      it is noted that for infants to understand communicative intent, they must have a
      concept of self and others as intentional agents. Evidence is reviewed to argue
      that this is not possible until 18-24 months of age. A leaner explanation of how
      infants might initially succeed in pointing tasks without understanding
      communicative intent is considered.

PMID- 17516999
TI  - Pointing behaviors in apes and human infants: a balanced interpretation.
AB  - This article presents a tentatively "balanced" view (i.e., midway between lean
      and rich interpretations) of pointing behavior in infants and apes, based upon
      the notion of intentional reading of behavior without simultaneous attribution of
      unobservable mental states. This can account for the complexity of infant
      pointing without attributing multilayered mindreading to infants. It can also
      account for ape pointing, which shares some of the complexities of infant
      pointing, but departs from it in other respects, notably in its range of motives
      and its focus upon the regulation of executive behavior. The article explores
      some explanations for these similarities and differences and calls for a new look
      at human infant communication unbiased by adult communication models.

PMID- 17517000
TI  - Infant pointing: communication to cooperate or communication to learn?
AB  - Tomasello, Carpenter, and Liszkowski (2007) present compelling data to support
      the view that infant pointing, from the outset, is communicative and deployed in
      many of the same situations in which adults would ordinarily point for one
      another, either to share their interest in something, or to informatively help
      the other person. This commentary concurs with the view that infant pointing is a
      communicative gesture, but challenges their interpretation of the motives behind
      pointing in 12-month-olds. An alternative account is proposed, according to which
      infant pointing is neither declarative nor imperative, but interrogative, and
      rather than being driven by the motive to share or help, it may serve a powerful
      cultural learning mechanism by which infants can obtain information from
      knowledgeable adults.

PMID- 17517001
TI  - Pointing sets the stage for learning language--and creating language.
AB  - Tomasello, Carpenter, and Liszkowski (2007) have argued that pointing gestures do
      much more than single out objects in the world. Pointing gestures function as
      part of a system of shared intentionality even at early stages of development. As
      such, pointing gestures form the platform on which linguistic communication
      rests, paving the way for later language learning. This commentary provides
      evidence that pointing gestures do establish a foundation for learning a language
      and, moreover, set the stage for creating a language.

PMID- 17517002
TI  - Depressive symptoms in young adults: the influences of the early home environment
      and early educational child care.
AB  - The relationship between depressive symptoms in young adults, the quality of the
      early home environment, and early educational child care was investigated in
      young adults randomly assigned to receive early childhood intervention in the
      Abecedarian study. Of the original 111 infants enrolled (98% African American),
      104 participated in an age-21 follow-up. Those who had early treatment reported
      fewer depressive symptoms. The protective effects of the early childhood program
      were further supported by a significant home environment by treatment
      interaction. Negative effects of lower quality home environments on young adult
      depressive symptoms were almost entirely offset by preschool treatment, whereas
      depressive symptoms increased as the quality of the early home environment
      decreased for those in the control group.

PMID- 17517003
TI  - Developmental changes in the coherence of essentialist beliefs about
      psychological characteristics.
AB  - Essentialism is the belief that certain characteristics (of individuals or
      categories) may be relatively stable, unchanging, likely to be present at birth,
      and biologically based. The current studies examined how different essentialist
      beliefs interrelate. For example, does thinking that a property is innate imply
      that the property cannot be changed? Four studies were conducted, examining how
      children (N=195, grades 1-7; ages 7-13) and adults (N=187) reason about familiar
      and novel social characteristics. By 3rd grade (9 years), children showed some
      coherence of essentialist beliefs. In contrast, younger children expected less
      interrelatedness among dimensions than older children or adults. These findings
      suggest that essentialist attributions at first consist of separate strands that
      children eventually link together into a more coherent understanding.

PMID- 17517004
TI  - Adolescents' cognitive and emotional responses to marital hostility.
AB  - Early adolescents' (11-14 years) responses to marital hostility were examined in
      a sample of 416 families. The cognitive-contextual perspective and emotional
      security hypothesis guided the study and 9 adolescent responses were identified.
      Prospective associations were examined in several structural equation models that
      included adolescent problems as outcomes. Self-blame and perceived threat
      uniquely mediated the association between Year 1 marital hostility and Year 3
      adolescent externalizing problems (p<.05). Self-blame, lower constructive
      representations, internalization of feelings, avoidance, and emotional
      dysregulation uniquely mediated the association between Year 1 marital hostility
      and Year 3 internalizing problems. Specific cognitive and emotionally based
      responses are important to understanding how martial hostility affects youth and
      need to be considered within an integrated model.

PMID- 17517005
TI  - Training parents to mediate sibling disputes affects children's negotiation and
      conflict understanding.
AB  - The effects of training parents to use formal mediation procedures in sibling
      disputes were examined in 48 families with 5- to 10-years-old children, randomly
      assigned to mediation and control conditions. Children whose parents were trained
      in mediation were compared with those whose parents intervened normally. Parents
      reported that children used more constructive conflict resolution strategies,
      compromised more often, and controlled the outcomes of conflicts more often in
      mediation families than in control families. Observations indicated less
      negativity in children's independent negotiations of recurrent conflicts, better
      understanding of the role of interpretation in assessing blame, and better
      knowledge of their siblings' perspectives in the mediation group. Thus, both
      social and social-cognitive gains resulted from experience with constructive
      conflict resolution.

PMID- 17517006
TI  - Doing the right thing: infants' selection of actions to imitate from observed
      event sequences.
AB  - Two studies were conducted to investigate how 14- to 16-month-old infants select
      actions to imitate from the stream of events. In each study, an experimenter
      demonstrated two actions leading to an interesting effect. Aspects of the first
      action were manipulated and whether infants performed this action when given the
      objects was observed. In both studies, infants were more likely to imitate the
      first action when it was physically necessary to generate the effect, and in
      Study 2 they were also more likely to imitate the action when it was socially
      cued. It seems that infants' own knowledge of space and causality as well as
      their sensitivity to others' social signals both contribute to their tendency to
      imitate actions.

PMID- 17517007
TI  - Peer selection and socialization effects on adolescent intercourse without a
      condom and attitudes about the costs of sex.
AB  - This study investigated peer selection and socialization effects on sexual
      behavior and attitudes using 1,350 15- to 18-year-old students participating in
      two waves of the National Longitudinal Study of Adolescent Health. Regarding
      socialization effects, friends' intercourse without condoms predicted later
      individual intercourse without condoms positively. Friends' attitudes about the
      costs of sex predicted later individual attitudes positively and intercourse
      without condoms negatively. The latter relation was stronger for females than for
      males. Regarding selection effects, individual attitudes predicted later friends'
      attitudes positively, but the strength of this effect varied by ethnicity. The
      results suggest that adolescents socialize friends to have similar sexual
      attitudes and behavior but tend to select friends based on similar attitudes
      rather than similar behaviors.

PMID- 17517008
TI  - Mind what mother says: narrative input and theory of mind in typical children and
      those on the autism spectrum.
AB  - In 2 studies mothers read wordless storybooks to their preschool-aged children;
      narratives were analyzed for mental state language. Children's theory-of-mind
      understanding (ToM) was concurrently assessed. In Study 1, children's (N=30; M
      age 3 years 9 months) ToM task performance was significantly correlated with
      mothers' explanatory, causal, and contrastive talk about cognition, but not with
      mothers' simple mentions of cognition. In Study 2, the same pattern was found in
      an older sample of typically developing children (N=24; M age 4 years 7 months),
      whereas for children on the autism spectrum (N=24; M age 6 years 7.5 months), ToM
      task performance was uniquely correlated with mothers' explanatory, causal, and
      contrastive talk about emotions.

PMID- 17517009
TI  - What is to be done? Children's ascriptions of conventional obligations.
AB  - It is often not apparent what people ought to do. Three experiments explored cues
      that children and adults may use to identify conventional obligations. Experiment
      1 addressed the hypothesis that young children identify obligations with expected
      outcomes. Although preschool-aged (4-5 years) children often expected
      consistency, they and school-aged (7-8 years) and adult participants indicated
      that obligations may be at odds with costs and benefits. In Experiment 2, all
      participants realized that people may have obligations they are unaware of.
      Preschool-aged children often used information about obligations to identify
      characters' beliefs. In Experiment 3, preschool but not school-aged children
      reliably identified obligations with the desires of authorities. The results are
      discussed in terms of expectations about canonical relations between mental
      states, outcomes, and obligations.

PMID- 17517010
TI  - Children's aesthetic understanding of photographic art and the quality of art
      related parent-child interactions.
AB  - This research was designed to examine the quality of children's aesthetic
      understanding of photographs, observe social interactions between parents and
      children in this aesthetic domain, and study whether qualitatively different
      dyadic interactions were associated with children's own aesthetic understanding.
      Parents and children (7-13 years; 40 dyads) individually completed measures of
      aesthetic understanding and jointly selected photographs for a souvenir
      scrapbook. Parents' artistic experience varied widely and was associated with
      their own performance on aesthetic understanding measures. Children's performance
      on the individual aesthetic tasks was related to age, but not to parents' art
      experience nor to the qualities of parent-child discussions of aesthetic
      concepts. Among both parents and children, artistic experience was associated
      with aesthetic preferences for photographs.

PMID- 17517011
TI  - Adolescent prosocial behavior: the role of self-processes and contextual cues.
AB  - Peer- and teacher-reported prosocial behavior of 339 6th-grade (11-12 years) and
      8th-grade (13-14 years) students was examined in relation to prosocial goals,
      self-processes (reasons for behavior, empathy, perspective taking, depressive
      affect, perceived competence), and contextual cues (expectations of peers and
      teachers). Goal pursuit significantly predicted prosocial behavior, and goal
      pursuit provided a pathway by which reasons for behavior were related to
      behavior. Reasons reflected external, other-focused, self-focused, and internal
      justifications for behavior; each reason was related to a unique set of self
      processes and contextual cues. Associations between prosocial outcomes and sex
      and race (Caucasian and African American) were mediated in part by self-processes
      and contextual cues. The implications of studying prosocial behavior from a
      motivational perspective are discussed.

PMID- 17517012
TI  - Development of gender attitude traditionality across middle childhood and
      adolescence.
AB  - The development of gender attitudes in 402 youth (201 firstborn and 201
      secondborn siblings) in 201 European American families was examined using data
      collected on seven occasions across 9 years. Pooling across siblings and using
      multilevel modeling, we examined gender attitude development from ages 7 to 19.
      Consistent with an ecological perspective, the combined effects of individual
      (i.e., sex, age, birth order) and contextual (i.e., parents' gender attitudes,
      sibling sex) characteristics predicted patterns of change. Although most youth
      declined in traditionality, the attitudes of firstborn boys with brothers and
      traditional parents became more traditional over time. No one longitudinal
      pattern captured the development of gender attitudes; trajectories varied as a
      function of contextual and personal characteristics.

PMID- 17517013
TI  - Salivary biomarker levels and diurnal variation: associations with medications
      prescribed to control children's problem behavior.
AB  - This study examined associations between medications prescribed to control
      children's problem behaviors and levels of, and diurnal variation in, salivary
      cortisol (C), testosterone (T), and dehydroepiandrosterone (DHEA). Saliva was
      collected in the morning, midday, and afternoon from 432 children ages 6-13
      years. Relative to a no-medication comparison group, children taking (1)
      antipsychotics had higher DHEA levels and flat C diurnal rhythms, (2) Ritalin or
      Adderall had flat T diurnal rhythms, (3) Concerta had higher T and DHEA levels,
      (4) antidepressants had flat DHEA diurnal rhythms, and (5) hypotensives had flat
      DHEA diurnal rhythms and higher T levels. Medications prescribed to control
      children's problem behaviors should be monitored in studies of the endocrine
      correlates and consequences of developmental psychopathology.

PMID- 17517014
TI  - Individual differences and the development of joint attention in infancy.
AB  - This study examined the development of joint attention in 95 infants assessed
      between 9 and 18 months of age. Infants displayed significant test-retest
      reliability on measures of following gaze and gestures (responding to joint
      attention, RJA) and in their use of eye contact to establish social attention
      coordination (initiating joint attention, IJA). Infants displayed a linear,
      increasing pattern of age-related growth on most joint attention measures.
      However, IJA was characterized by a significant cubic developmental pattern.
      Infants with different rates of cognitive development exhibited different
      frequencies of joint attention acts at each age, but did not exhibit different
      age-related patterns of development. Finally, 12-month RJA and 18-month IJA
      predicted 24-month language after controlling for general aspects of cognitive
      development.

PMID- 17517015
TI  - Change in atypical maternal behavior predicts change in attachment
      disorganization from 12 to 24 months in a high-risk sample.
AB  - This longitudinal study examined links between disorganization and atypical
      maternal behavior at 12 and 24 months in 71 adolescent mother-child dyads.
      Organized attachment and maternal not disrupted behavior were more stable than
      disorganization and disrupted behavior, respectively. At both ages,
      disorganization and maternal disrupted behavior were significantly correlated.
      Change in atypical maternal behavior predicted change in disorganization across
      time. The results provide substantial support for extant theories linking
      anomalous maternal behavior to the development of disorganized attachment. The
      Interesting-but-Scary paradigm, introduced in this study, promises to be a useful
      tool for assessing attachment and maternal behavior in toddlerhood.

PMID- 17517016
TI  - Why are hyperactivity and academic achievement related?
AB  - Although a negative association between hyperactivity and academic achievement is
      well documented, little is known about the genetic and/or environmental
      mechanisms responsible for the association. The present study explored links
      between parent and teacher ratings of hyperactive behavior problems and teacher
      assessed achievement in a sample of 1,876 twin pairs (mean age 7.04 years). The
      results did not differ across rater, nor were there significant differences
      between males or females or for twins in the same or different classrooms.
      Hyperactivity was significantly correlated with achievement. Multivariate model
      fitting analyses revealed significant genetic and nonshared environmental
      covariance between the two phenotypes. In addition, bivariate heritabilities were
      substantial, indicating that the phenotypic correlations between hyperactivity
      and achievement were largely mediated by genetic influences.

PMID- 17517017
TI  - Developmental trends for object and spatial working memory: a psychophysiological
      analysis.
AB  - This study examined developmental trends in object and spatial working memory
      (WM) using heart rate (HR) to provide an index of covert cognitive processes.
      Participants in 4 age groups (6-7, 9-10, 11-12, 18-26, n=20 each) performed
      object and spatial WM tasks, in which each trial was followed by feedback.
      Spatial WM task performance reached adult levels before object WM task
      performance. The differential developmental trends for object and spatial WM
      found in this study are taken to suggest that these WM components are separable.
      Negative performance feedback elicited HR slowing that was more pronounced for
      adults than for children. The development of performance monitoring as indexed by
      covert HR slowing following performance feedback contributes to WM performance.

PMID- 17517018
TI  - Cultural variation in children's social organization.
AB  - This article examines how 31 triads of 6- to 10-year-old children from 3 cultural
      backgrounds organized their interactions while folding Origami figures. Triads of
      children whose families had immigrated to the United States from indigenous
      heritage regions of Mexico (and whose mothers averaged only 7 grades of
      schooling) coordinated more often as an ensemble, whereas triads of European
      heritage U.S. children whose mothers had extensive schooling more often engaged
      dyadically or individually. When the European heritage children did engage as an
      ensemble, this often involved chatting rather than nonverbal conversation
      regarding folding, which was more common among the Mexican heritage children.
      Mexican heritage U.S. triads whose mothers had extensive schooling showed an
      intermediate pattern or resembled the European heritage children.

PMID- 17517019
TI  - Improbable or impossible? How children reason about the possibility of
      extraordinary events.
AB  - The present study investigated the development of possibility-judgment strategies
      between the ages of 4 and 8. In Experiment 1, 48 children and 16 adults were
      asked whether a variety of extraordinary events could or could not occur in real
      life. Although children of all ages denied the possibility of events that adults
      also judged impossible, children frequently denied the possibility of events that
      adults judged improbable but not impossible. Three additional experiments varied
      the manner in which possibility judgments were elicited and confirmed the
      robustness of preschoolers' tendency to judge improbable events impossible.
      Overall, it is argued that children initially mistake their inability to imagine
      circumstances that would allow an event to occur for evidence that no such
      circumstances exist.

PMID- 17517022
TI  - Entertaining Apollo or Dionysus? Either way we need to pay the bills . . .

PMID- 17517024
TI  - Caregivers' experiences of exposure to violence in services for people with
      learning disabilities.
AB  - Exposure to violence is a commonly encountered problem in services for people
      with learning disabilities; Swedish studies have reported that 51-61% of
      caregivers are exposed to violence each year, and caregivers describe violence as
      being a 'normal' part of their working life. To illuminate the experience of
      being exposed to violence, we performed 50 narrative interviews with 44
      caregivers working in services for people with learning disabilities. The tape
      recorded interviews were transcribed verbatim and subjected to qualitative
      content analysis. The main findings indicate that caregivers' experiences of
      being exposed to violence can be related to two themes: falling apart, and
      keeping it together. Falling apart includes feelings of fear, powerlessness,
      sadness, anger and timelessness, while keeping it together concerns pleasure,
      respect, self-reflection and habituation. Destructive experiences of falling
      apart are balanced by a more constructive view of the situation, with the aim of
      respecting the resident as a whole person, and keeping the situation, and the
      caregivers themselves, together.

PMID- 17517025
TI  - The nursing gaze: power relations in a study of nurse-resident interactions in
      learning disability.
AB  - The researchers observed nurse-resident interactions in learning disability units
      in Hong Kong and interviewed a purposeful sample of nurses who had varying levels
      of interaction. The median interaction rate between nurses and residents was
      27.5% with most interactions relating to physical care. When not interacting with
      residents, nurses performed administrative tasks. Factors that influenced nurses'
      interactions revolve around their orientation to a new clinical setting, stresses
      in the care setting and nurses' coping strategies, contextual constraints, and
      nurses' prioritization of care. Support for Goffman's self-mortification
      principle, Foucault's notion of the clinical gaze and infantilism theory were
      evident in the practice of the nurses studied.

PMID- 17517026
TI  - Family work in first-onset psychosis: a literature review.
AB  - Family intervention may be helpful for people with psychosis. We reviewed the
      literature for family intervention for people with a first-onset psychosis. There
      is limited and conflicting evidence of the efficacy of family intervention for
      this population. Definitive randomized controlled trials are required to
      establish the efficacy. At this time, evidence suggests that in High Expressed
      Emotion (EE) families, family intervention is a possible effective intervention.
      We suggest caution in families with Low EE as one study suggests that in Low EE
      families, family intervention can increase the levels of EE.

PMID- 17517027
TI  - Encounters in a locked psychiatric ward environment.
AB  - This focused ethnographic study aims at describing encounters in the healthcare
      environment on a locked psychiatric ward. It was carried out in Sweden on an
      acute psychiatric ward for patients with affective and eating disorders. Data
      were collected through participant observations and informal interviews, and
      analysed by qualitative content analysis. The result shows that the healthcare
      environment on this locked psychiatric ward offered a space for encounters
      between people, in a continuum from professional care to private meetings and
      social events. It included joy and friendship as well as unintentional insights
      into other patients' suffering. The characteristics of the encounters formed
      three themes: the caring relationship, the uncaring relationship and the
      unrecognized relationship. The caring and the uncaring relationship concerned
      relationships between staff and patients or their next of kin. These revealed
      contrasting qualities such as respect and flexibility as well as lack of respect
      and mistrust. The unrecognized relationship theme visualized the patients'
      relationships with each other and included both supportive and intrusive elements
      that were probably significant for the outcome of care. The unrecognized
      relationship contributes with new knowledge about conditions for patients in
      inpatient care, and indicates that the patients' relationships with each other
      merit greater attention.

PMID- 17517028
TI  - Flexible observation: guidelines versus reality.
AB  - This paper reports a small-scale pilot study to introduce flexible observation of
      patients in an acute psychiatric clinical area where nurses have increased
      autonomy to make such decisions. The Clinical Resource and Audit Group document
      'Engaging People: Observation of People with Acute Mental Health Problems: A Good
      Practice Statement' outlines very clearly the observation levels that should be
      used in acute psychiatric areas in Scotland. It also states clearly who is
      responsible for conducting different parts of the observation process and how
      such observation procedures should be conducted. The available literature
      recommends three observation levels with engagement and considers that
      intermittent or time period checks are unsafe. A small-scale action research
      pilot study was conducted over a period of 6 months with individual incidents (n
      = 57) of patients requiring increased or decreased observation levels being
      included in the study. There were no exclusion criteria and this was a total
      sample in one clinical area. The results were analysed using the Statistical
      Package for the Social Sciences v.14.0 using non-parametric statistics and chi
      square. The results indicated there has been a shift away from doctors deciding
      on the levels of observation towards multidisciplinary or nursing decisions
      regarding this aspect of care. During the pilot, there was a gradual shift away
      from high levels of observation. Those that were placed on increased levels of
      observation were on them for a much shorter time than previously and staff
      generally found the new recording system to be more practical. There were a
      number of 'sub-levels' of general and constant observation in use. Over the
      years, recording has suffered from incomplete information and this pilot is no
      different with 56% (n = 34) of the recording sheets had at least one section of
      clinical information incomplete or not filled in at all. Despite the guidelines
      and the subsequent training of staff in the clinical area, some nursing staff
      were not participating as fully as they might in the decision-making process.
      Fewer patients were being placed on increased observation levels. Those that were
      placed on observation were on them for a much shorter time than previously and
      staff generally found the new recording system to be more practical.

PMID- 17517029
TI  - The lived experience of community mental health nurses working with people who
      have dual diagnosis: a phenomenological study.
AB  - Dual diagnosis (the combination of mental health and substance misuse problems)
      is a significant facing mental health nurses in the UK. The purpose of the study
      was to describe the lived experience of community mental health nurses working
      with people who have a dual diagnosis. A phenomenological approach was us and a
      purposive sample of seven community mental health nurses with experience of
      working with people with a dual diagnosis was selected. Data were collected
      through audiotaped, semi-structured interviews lasting approximately 1 h in
      duration and analysed using Colaizzi's (1978) method. Thirteen theme clusters
      relating to three major themes were identified: (1) difficulties in understanding
      the concept of dual diagnosis; (2) feeling deskilled when working with people who
      have a dual diagnosis; (3) struggling to work in a system which seeks to avoid
      people with dual diagnosis. Recommendations regarding the need for increased
      joint working between professionals, improved education and further research are
      made.

PMID- 17517030
TI  - Early life experiences and their impact on our understanding of depression.
AB  - This paper presents part of a larger Grounded Theory study, which was designed to
      capture a sample of people's perceptions of living with or, caring for,
      individuals with depression. Data were collected from a focus group consisting of
      people with depression (n = 7). In-depth one-to-one interviews were undertaken
      with eight further respondents (n = 8). Purposeful sampling was used initially.
      Thereafter, in keeping with one of the key tenets of grounded theory, theoretical
      sampling was used. The emergent concepts were pursued until saturation occurred.
      The constant comparative approach was used to analyse the data together with the
      NVivo qualitative analysis software package. This paper focuses on the
      respondents' perceptions of the pre-diagnosis, depression encounter. The key
      category that emerged was 'the pre-diagnosis phase of depression and the now
      experience'. Five key themes surfaced within this category: (1) negative impact
      significant life events; (2) self-blame; (3) personal characteristics; (4) pre
      diagnosis, depression unknowingness; and (5) pre-help seeking. The findings
      suggest that those in the field of human services need to better understand the
      lived experience of people with depression, in order to provide holistic
      treatment and care.

PMID- 17517031
TI  - The immigration experience among elderly Korean immigrants.
AB  - The purpose of this preliminary, qualitative study was to describe elderly Korean
      immigrants' perception of stressors they experienced through immigration and the
      acculturation process. The methodology used was naturalistic inquiry, a
      descriptive approach used to elicit the elderly immigrants' own perception of
      their immigration and acculturation experiences. The six elderly Korean
      immigrants were interviewed via a semi-structured, open-ended interview guide.
      The main stressors identified by the subjects as a result of adjusting to life in
      the United States were language barriers, isolation and loneliness, fear of
      dependence upon their children, fear of being a burden, financial problems,
      transportation problems, discrimination, and fear of death. These Korean elders
      also perceived changes in the traditional family values of respect for elders and
      support for the aged. The results of this research help to provide an
      understanding of the immigration and acculturation experiences of elderly Korean
      immigrants.

PMID- 17517032
TI  - Uncovering the sexual self in people with schizophrenia.
AB  - Sexuality is a vital component of the self. Yet, there is a dearth of research
      literature that explores the sexuality of people with schizophrenia. The purpose
      of this study was to understand how people with schizophrenia experience and
      perceive their sexuality. Using grounded theory methodology, the study recruited
      five men and five women with schizophrenia-spectrum disorders who lived
      independently in the community. These participants were interviewed regarding
      their subjective sense of their own sexuality. The findings suggested that people
      with schizophrenia integrate sexuality into their sense of self. Although the
      illness affected various aspects of their sexual lives, many participants were
      able to develop and maintain meaningful intimate relationships, as well as
      construct their own definitions and personal meanings of sexuality. Furthermore,
      participants described dealing with the impact of schizophrenia in the context of
      managing their illness. These findings have implications for clinical practice
      and recovery of people with schizophrenia.

PMID- 17517033
TI  - Delivering the choice agenda as a framework to manage adverse effects: a mental
      health nurse perspective on prescribing psychiatric medication.
AB  - The article describes the clinical management of a patient referred, with a
      diagnosis of schizophrenia, who experienced adverse effects associated with an
      elevated prolactin level. A reflective model was adopted to inform the new
      learning which emerged from the clinical scenario. It highlights that Mental
      Health Nurse Supplementary Prescribers need to develop a prescribing value base
      underpinned by choice in addition to advanced technical skills to manage
      unhelpful effects of medication.

PMID- 17517036
TI  - Aging and cancer cell biology, 2007.
AB  - This Hot Topics review, the second in a new Aging Cell series, discusses articles
      published in the last year that have stimulated new ideas about the tangled
      relationship of aging to cancer cell biology. The year's highlights include
      reports on the ability of Mdm2 mutations to diminish risks of cancer in aging
      mice, on proliferative competition between oncogenic cells and bone marrow stem
      cells, and on the role of metalloproteinases in overcoming age-associated
      barriers to tumor invasion. Of particular interest were three articles showing
      that diminished activity of the tumor-suppressor gene p16/INK4a, while increasing
      the risk of cancer mortality, can lead to improved function in several varieties
      of age-sensitive stem cells.

PMID- 17517037
TI  - Role of calcium in normal aging and neurodegeneration.

PMID- 17517038
TI  - The importance of being subtle: small changes in calcium homeostasis control
      cognitive decline in normal aging.
AB  - Aging is a complex, multifactorial process. One of the features of normal aging
      of the brain is a decline in cognitive functions and much experimental attention
      has been devoted to understanding this process. Evidence accumulated in the last
      decade indicates that such functional changes are not due to gross morphological
      alterations, but to subtle functional modification of synaptic connectivity and
      intracellular signalling and metabolism. Such synaptic modifications are
      compatible with a normal level of activity and allow the maintenance of a certain
      degree of functional reserve. This is in contrast to the changes in various
      neurodegenerative diseases, characterized by significant neuronal loss and
      dramatic and irreversible functional deficit. This whole special issue has been
      initiated with the intention of focusing on the processes of normal brain aging.
      In this review, we present data that shows how subtle changes in Ca(2+)
      homeostasis or in the state of various Ca(2+)-dependent processes or molecules,
      which occur in aging can have significant functional consequences.

PMID- 17517039
TI  - Age-dependent changes in Ca2+ homeostasis in peripheral neurones: implications
      for changes in function.
AB  - Calcium ions represent universal second messengers within neuronal cells
      integrating multiple cellular functions, such as release of neurotransmitters,
      gene expression, proliferation, excitability, and regulation of cell death or
      apoptotic pathways. The magnitude, duration and shape of stimulation-evoked
      intracellular calcium ([Ca2+]i) transients are determined by a complex interplay
      of mechanisms that modulate stimulation-evoked rises in [Ca2+]i that occur with
      normal neuronal function. Disruption of any of these mechanisms may have
      implications for the function and health of peripheral neurones during the aging
      process. This review focuses on the impact of advancing age on the overall
      function of peripheral adrenergic neurones and how these changes in function may
      be linked to age-related changes in modulation of [Ca2+]i regulation. The data in
      this review suggest that normal aging in peripheral autonomic neurones is a
      subtle process and does not always result in dramatic deterioration in their
      function. We present studies that support the idea that in order to maintain cell
      viability peripheral neurones are able to compensate for an age-related decline
      in the function of at least one of the neuronal calcium-buffering systems, smooth
      endoplasmic reticulum calcium ATPases, by increased function of other calcium
      buffering systems, namely, the mitochondria and plasmalemma calcium extrusion.
      Increased mitochondrial calcium uptake may represent a 'weak point' in cellular
      compensation as this over time may contribute to cell death. In addition, we
      present more recent studies on [Ca2+]i regulation in the form of the modulation
      of release of calcium from smooth endoplasmic reticulum calcium stores. These
      studies suggest that the contribution of the release of calcium from smooth
      endoplasmic reticulum calcium stores is altered with age through a combination of
      altered ryanodine receptor levels and modulation of these receptors by neuronal
      nitric oxide containing neurones.

PMID- 17517040
TI  - Calcium buffering systems and calcium signaling in aged rat basal forebrain
      neurons.
AB  - Disturbances of neuronal Ca2+ homeostasis are considered to be important
      determinants of age-related cognitive impairment. Cholinergic neurons of the
      basal forebrain (BF) are principal targets of decline associated with aging and
      dementia. During the last several years, we have attempted to link these concepts
      in a rat model of 'normal' aging. In this review, we will describe some changes
      that we have observed in Ca2+ signaling of aged BF neurons and the reversal of
      one of these changes by dietary caloric restriction. Our evidence supports a
      scenario in which subtle changes in the properties of voltage-gated Ca2+ channels
      result in increased Ca2+ influx during aging. This increased Ca2+, in turn,
      triggers an increase in rapid Ca2+ buffering in the somatic compartment of aged
      BF neurons. However, this nominal 'compensation', along with other changes in
      Ca2+ handling machinery (notably mitochondria) alters the Ca2+ signal with age in
      a way that is dependent on the magnitude of the Ca2+ load. By combining whole
      cell patch clamp electrophysiology, ratiometric Ca2+-sensitive microfluorimetry
      and single-cell reverse transcription-polymerase chain reaction, we have
      determined that age-related rapid buffering changes are present in identified
      cholinergic BF neurons and that these changes can be prevented by a caloric
      restriction dietary regimen. Because caloric restriction extends lifespan and
      retards the progression of age-related dysfunction, these findings suggest that
      increased Ca2+ buffering in cholinergic neurons may be relevant to cognitive
      decline during normal aging. Importantly, calcium homeostatic mechanisms of BF
      cholinergic neurons are amenable to dietary interventions that could promote
      cognitive health during aging.

PMID- 17517041
TI  - Calcium homeostasis and modulation of synaptic plasticity in the aged brain.
AB  - The level of intracellular Ca2+ plays a central role in normal and pathological
      signaling within and between neurons. These processes involve a cascade of events
      for locally raising and lowering cytosolic Ca2+. As the mechanisms for age
      related alteration in Ca2+ dysregulation have been illuminated, hypotheses
      concerning Ca2+ homeostasis and brain aging have been modified. The idea that
      senescence is due to pervasive cell loss associated with elevated resting Ca2+
      has been replaced by concepts concerning changes in local Ca2+ levels associated
      with neural activity. This article reviews evidence for a shift in the sources of
      intracellular Ca2+ characterized by a diminished role for N-methyl-D-aspartate
      receptors and an increased role for intracellular stores and voltage-dependent
      Ca2+ channels. Physiological and biological models are outlined, which relate a
      shift in Ca2+ regulation with changes in cell excitability and synaptic
      plasticity, resulting in a functional lesion of the hippocampus.

PMID- 17517042
TI  - Alterations in intrinsic neuronal excitability during normal aging.
AB  - Normal aging subjects, including humans, have difficulty learning hippocampus
      dependent tasks. For example, at least 50% of normal aging rabbits and rats fail
      to meet a learning criterion in trace eyeblink conditioning. Many factors may
      contribute to this age-related learning impairment. An important cause is the
      reduced intrinsic excitability observed in hippocampal pyramidal neurons from
      normal aging subjects, as reflected by an enlarged postburst
      afterhyperpolarization (AHP) and an increased spike-frequency adaptation
      (accommodation). In this review, we will focus on the alterations in the AHP and
      accommodation during learning and normal aging. We propose that age-related
      increases in the postburst AHP and accommodation in hippocampal pyramidal neurons
      play an integral role in the learning impairment observed in normal aging
      subjects.

PMID- 17517044
TI  - Re: patient satisfaction with psychiatric inpatient care.

PMID- 17517043
TI  - Oxidative stress and aberrant signaling in aging and cognitive decline.
AB  - Brain aging is associated with a progressive imbalance between antioxidant
      defenses and intracellular concentrations of reactive oxygen species (ROS) as
      exemplified by increases in products of lipid peroxidation, protein oxidation,
      and DNA oxidation. Oxidative conditions cause not only structural damage but also
      changes in the set points of redox-sensitive signaling processes including the
      insulin receptor signaling pathway. In the absence of insulin, the otherwise low
      insulin receptor signaling is strongly enhanced by oxidative conditions.
      Autophagic proteolysis and sirtuin activity, in turn, are downregulated by the
      insulin signaling pathway, and impaired autophagic activity has been associated
      with neurodegeneration. In genetic studies, impairment of insulin receptor
      signaling causes spectacular lifespan extension in nematodes, fruit flies, and
      mice. The predicted effects of age-related oxidative stress on sirtuins and
      autophagic activity and the corresponding effects of antioxidants remain to be
      tested experimentally. However, several correlates of aging have been shown to be
      ameliorated by antioxidants. Oxidative damage to mitochondrial DNA and the
      electron transport chain, perturbations in brain iron and calcium homeostasis,
      and changes in plasma cysteine homeostasis may altogether represent causes and
      consequences of increased oxidative stress. Aging and cognitive decline thus
      appear to involve changes at multiple nodes within a complex regulatory network.

PMID- 17517049
TI  - Identification of the human cytochromes P450 catalysing the rate-limiting
      pathways of gliclazide elimination.
AB  - AIMS: To identify the human cytochrome P450 (CYP) enzymes responsible for the
      formation of the 6beta-hydroxy (6beta-OHGz), 7beta-hydroxy (7beta-OHGz) and
      hydroxymethyl (MeOH-Gz) metabolites of gliclizide (Gz). METHODS: 6beta-OHGz,
      7beta-OHGz and MeOH-Gz formation by human liver microsomes and a panel of
      recombinant human P450s was measured using a high-performance liquid
      chromatography procedure, and the kinetics of metabolite formation was determined
      for each pathway. Effects of prototypic CYP enzyme selective inhibitors were
      characterized for each of the microsomal metabolic pathways. RESULTS: Microsomes
      from six human livers converted Gz to its 6beta-OHGz, 7beta-OHGz, and MeOH-Gz
      metabolites, with respective mean (+/- SD) K(m) values of 461 +/- 139, 404 +/-
      143 and 334 +/- 75 microm and mean V(max) values of 130 +/- 55, 82 +/- 31 and 268
      +/- 115 pmol min(-1) mg(-1), respectively. V(max)/K(m) ratios for the microsomal
      reactions parallelled relative metabolite formation in vivo. Sulfaphenazole
      inhibited microsomal 6beta-OHGz, 7beta-OHGz and MeOH-Gz formation by 87, 83 and
      64%, respectively, whereas S-mephenytoin caused significant inhibition (48%) of
      only MeOH-Gz formation. Recombinant CYP2C9, CYP2C18 and CYP2C19 catalysed all
      hydroxylation pathways, whereas CYP2C8 formed only 6beta-OHGz and 7beta-OHGz.
      CONCLUSION: Taken together, the results indicate that CYP2C9 is the major
      contributor to Gz metabolic clearance, although CYP2C19 may also be involved in
      MeOH-Gz formation (the major metabolic pathway). Factors known to influence
      CYP2C9 activity will provide the main source of variability in Gz
      pharmacokinetics.

PMID- 17517051
TI  - Alcohol dehydrogenase and aldehyde dehydrogenase polymorphisms and colorectal
      cancer: the Fukuoka Colorectal Cancer Study.
AB  - Alcohol dehydrogenase and aldehyde dehydrogenase are key enzymes in alcohol
      metabolism and therefore may be of importance to colorectal cancer development.
      The present case-control study was conducted to determine the influence of ADH2,
      ADH3 and ALDH2 polymorphisms in Fukuoka, Japan, with 685 incident cases of
      histologically confirmed colorectal adenocarcinomas and 778 community controls
      selected randomly from the study area. Alcohol use was ascertained by in-person
      interview. Statistical adjustment was made for sex, age class, area, and alcohol
      use. Individuals with the allele 47Arg of the ADH2 polymorphism (slow
      metabolizers) had a statistically significant increase in risk, with an adjusted
      OR of 1.32 (95% CI = 1.07-1.63), compared with those having the ADH2*47His/His
      genotype. This association was not affected by the level of alcohol consumption.
      The ADH3 polymorphism showed no measurable association with the risk of
      colorectal cancer on either overall analysis or stratified analysis with alcohol
      use. The heterozygous ALDH2*487Glu/Lys genotype was not associated with an
      increase in the risk of colorectal cancer (adjusted OR 0.89, 95% CI = 0.71-1.13)
      compared with the ALDH2*487Glu/Glu genotype. Rather unexpectedly, the homozygous
      ALDH2*487Lys/Lys genotype was related to a statistically significantly decreased
      risk of colorectal cancer (adjusted OR 0.55, 95% CI = 0.33-0.93). It is unlikely
      that acetaldehyde metabolism determined by ALDH2 polymorphism contributes to the
      risk of colorectal cancer, whereas the role of ADH2 polymorphism deserves further
      investigation.

PMID- 17517050
TI  - Minimal effect of MDR1 and CYP3A5 genetic polymorphisms on the pharmacokinetics
      of indinavir in HIV-infected patients.
AB  - AIMS: The protease inhibitor indinavir is characterized by an important
      interindividual pharmacokinetic variability, which results from the actions of
      the metabolizing enzymes cytochrome P450 (CYP) 3A and the multidrug efflux pump P
      glycoprotein (P-gp), encoded by MDR1. Using a population pharmacokinetic
      approach, we investigated the effect of several MDR1 and CYP3A5 polymorphisms on
      the pharmacokinetic parameters of indinavir in HIV-infected patients. METHODS:
      Twenty-eight patients receiving indinavir alone or together with ritonavir were
      included. Indinavir pharmacokinetics were studied over a 12 h interval. Genetic
      polymorphisms were assessed by real-time PCR assays and direct sequencing for
      MDR1 and by PCR-SSCP analysis for CYP3A5. RESULTS: The pharmacokinetics of
      indinavir were best described by a one-compartment model with first-order
      absorption. In the final model, the MDR1 C3435T genotype and ritonavir were
      identified as statistically significant covariates (P </= 0.001) for the
      absorption rate constant (95% confidence interval on the difference between CC
      and CT genotype 0.37, 5.53) and for clearance (95% confidence interval on the
      difference 5.8, 26.2), respectively. Patients with the CYP3A5*3/*3 genotype
      receiving indinavir alone had a 31% decrease in the indinavir clearance rate
      compared with patients carrying the CYP3A5*1/*3 genotype. CONCLUSIONS: The MDR1
      C3435T genotype affects the absorption constant of indinavir suggesting that P-gp
      may be implicated in its pharmacokinetic variability. Through its inhibition of
      CYP3A and P-gp, ritonavir could attenuate the pharmacokinetic variability linked
      to genetic differences, reducing significantly the interindividual variability of
      indinavir. However, genotyping MDR1 and/or CYP3A5 to optimize protease inhibitor
      boosted regimens does not seem clinically relevant.

PMID- 17517052
TI  - Clinical trial of autologous formalin-fixed tumor vaccine for glioblastoma
      multiforme patients.
AB  - A pilot study was performed to investigate the safety and feasibility of
      autologous formalin-fixed tumor vaccines (AFTV) and the clinical responses to
      these vaccines by glioblastoma multiforme (GBM) patients. Twelve primary GBM
      patients were recruited. Eight had recurrent disease while four had been treated
      for primary disease but retained a visible tumor mass. AFTV were prepared from
      formalin-fixed and/or paraffin-embedded tumor tissue obtained upon surgery and
      premixed with original adjuvant materials. The patients were given three five
      site intradermal inoculations at weekly intervals. A delayed-type
      hypersensitivity test was performed before and after each vaccination. In
      addition, the tumor tissues were subjected to immunohistochemical analysis to
      determine whether MIB-1, p53, and major histocompatibility complex (MHC) class-I
      complex expression could predict the response to the treatment. The treatment was
      well tolerated, with only local erythema, induration, and low-grade fever being
      reported. Of the 12 patients, one showed a complete response, one showed a
      partial response, two showed minor responses, one had stable disease, and seven
      exhibited progressive disease. The median survival period was 10.7 months from
      the initiation of the AFTV treatment but three of the five responders survived
      for 20 months or more after AFTV inoculation. Low p53 and high MHC class-I
      expression by the tumor may help predict the efficacy of this therapy. Thus, the
      AFTV is safe and feasible, and could significantly improve the outcome of GBM.
      Further clinical investigations to confirm this are highly desirable.

PMID- 17517053
TI  - Sensitivity of human cells bearing oncogenic mutant kit isoforms to the novel
      tyrosine kinase inhibitor INNO-406.
AB  - The activity of the novel tyrosine kinase inhibitor INNO-406 against human cells
      with mutated KIT was investigated. Human mast cell (HMC)-1.1 cells with
      juxtamembrane domain mutation V560G, and HMC-1.2 cells with both V560G and the
      kinase domain mutation D816V, were treated with INNO-406 (0.02-5.00 microM) or
      imatinib for 72 h. INNO-406 and imatinib were equipotent against HMC-1 cells
      regarding cell proliferation (IC50 51 nM and 75 nM, respectively), inhibition of
      KIT phosphorylation, and induction of apoptosis. In contrast, neither drug was
      effective against HMC-1.2 cells at the dose range tested. The present results
      suggest clinical potential for INNO-406 in KIT V560G-expressing malignancies.

PMID- 17517054
TI  - Involvement of reactive oxygen species in multidrug resistance of a vincristine
      selected lymphoblastoma.
AB  - Our previous study identified a vincristine-selected multidrug resistance (MDR)
      cell line, HOB1/VCR, derived from a lymphoblastoma HOB1. The HOB1/VCR cells are
      resistant to typical MDR drugs and are cross-resistant to P-glycoprotein
      independent drugs such as cisplatin (cis-diamminedichloroplatinum [II]). The
      mechanism of this atypical MDR phenotype is uncertain. The present study provides
      evidence regarding the contribution of reactive oxygen species (ROS) to the
      resistance of cells in response to treatments (vincristine, cisplatin and H2O2).
      Notably, the HOB1/VCR cells were cross-resistant to H2O2. High levels of ROS
      formed in both sensitive and HOB1/VCR cells by H2O2, and moderate levels of ROS
      were generated by treatment with cisplatin and vincristine. The ROS level in
      HOB1/VCR cells was lower than that in sensitive cells following treatments. The
      ROS level was reduced markedly by a non-toxic concentration of N-acetyl-L
      cysteine, a ROS scavenger, in drug-treated cells, and was correlated with reduced
      cytotoxicity. Furthermore, concentrations of glutathione and glutathione
      peroxidase, but not superoxide dismutase and catalase, increased in HOB/VCR
      cells. The DL-buthionine-[S,R]-sulfoximine inhibited formation of glutathione and
      sensitized both cell types to treatments. Therefore, overexpression of an H2O2
      reducing system, glutathione-glutathione peroxidase, has a role in resistance.
      Experimental results further demonstrate that ROS is likely a primary signal in
      the acquisition of the MDR phenotype and therefore a potential target when
      designing drugs for chemoresistance.

PMID- 17517055
TI  - Dose-dependent synergy of Th1-stimulating cytokines on bacille Calmette-Guerin
      induced interferon-gamma production by human mononuclear cells.
AB  - Successful bacille Calmette-Guerin (BCG) immunotherapy of bladder cancer depends
      on the proper induction of a T helper-type 1 (Th1) immune response. In this study
      we investigated the possible involvement of Th1-stimulating cytokines in BCG
      induced interferon (IFN)-gamma production as well as their potential roles in
      enhancing BCG-induced IFN-gamma from human peripheral blood mononuclear cells
      (PBMCs). BCG efficiently induced IFN-gamma production by PBMCs in a dose
      dependent manner. Neutralization of endogenous cytokines interleukin (IL)-2, IL
      12 and IFN-alpha reduced BCG-induced IFN-gamma by 38%, 67% and 49%, respectively.
      Although single recombinant (r) IL-2, rIL-12 and rIFN-alpha induced no or a
      marginal amount of IFN-gamma, a combination of any two or three cytokines
      increased IFN-gamma production. When BCG (a subsaturated dose) was combined with
      mono, dual or triple cytokines, a synergy on IFN-gamma production was observed.
      Such a synergy was readily achievable even when minimal or low doses of cytokines
      were used. No saturation of IFN-gamma production was observed even when a
      subsaturated BCG dose was combined with very high doses of cytokines. A robust
      IFN-gamma production was also observed when a minimal BCG dose was combined with
      minimal doses of triple cytokines. In addition, we demonstrated that IL-2- and
      IFN-alpha-expressing rBCGs were superior to wild-type BCG for PBMC IFN-gamma
      induction and that combination of both rBCGs showed a synergy in IFN-gamma
      production. Taken together, these results suggest that combination of BCG with
      certain exogenous or endogenous (expressed by rBCGs) Th1-stimulating cytokines is
      a rational candidate for further study in bladder cancer treatment.

PMID- 17517056
TI  - Early functional loading of sand-blasted and acid-etched (SLA) Straumann implants
      following immediate placement in maxillary extraction sockets. Clinical and
      radiographic result.
AB  - OBJECTIVES: To present the clinical and radiographic outcome of early loading of
      implants inserted into fresh extraction sockets and to present a treatment
      protocol for early loading of the implants by 'passively fitting' abutment-free
      permanent fixed complete dentures (implant FCDs). MATERIAL AND METHODS: The study
      included 19 dentate patients treatment planned for extraction of all remaining
      maxillary teeth. In all, 116 Straumann-implants with sandblasted, large grit and
      acid etched (SLA) surface were placed: 77 (66%) inserted in fresh extraction
      sockets and 39 (34%) in healed bone. At least six implants were placed in each
      maxilla. One hundred and ten implants were loaded by permanent FCDs within 10
      days after placements and six after 14 days. The patients were reexamined
      clinically and radiographically after 2-3 years of clinical function. All FCDs
      were removed for control of implant stability and evaluation of the peri-implant
      status. RESULTS: Owing to framework fracture, two implants were lost,
      corresponding to a failure rate of 2%. The radiographic measurements after 2-3
      years did not reveal any difference in bone height mesial and distal of the
      implants placed in extraction sockets vs. in healed bone. This was interpreted as
      a bone gain around the implants placed in extraction sockets and a slight bone
      loss around the implants placed in healed bone. CONCLUSION: Early functional
      loading of SLA-surfaced implants following immediate placement in maxillary
      extraction sockets by rigid and passively fitting permanent implant FCDs is a
      reliable treatment alternative.

PMID- 17517057
TI  - A comparison of bone mineral density in the spine, hip and jaws of edentulous
      subjects.
AB  - OBJECTIVES: The aim was to investigate the relationship between bone mineral
      density (BMD) of the jaws (mandible and maxilla) and other skeletal sites. In
      addition, the influence of gender, smoking and the number of years without
      natural teeth were examined. MATERIALS AND METHODS: 18 edentulous patients (9
      females, 9 males) with a mean age of 67.1 (sd 12.6) years had DXA scans to assess
      the BMD of the lumbar spine and hip, together with the ramus, body and symphysis
      of the mandible and the anterior of the maxilla. RESULTS: BMD values for the
      ramus were similar to those for the femur but significantly lower than the lumbar
      spine. The body and anterior mandible had higher values and the anterior maxilla
      lower values than both the femur and ramus. The ramus BMD showed moderately
      strong relationships with the standard measures of BMD in the spine and hip, but
      the BMD of other areas of the jaws showed no relationship with skeletal sites.
      The BMD for both the hip and the ramus showed an inverse relationship with
      increasing age. There was no statistically significant relationship between BMD
      of hip, spine and jaw and either years edentulous or cigarette years. (207)
      CONCLUSIONS: Although the ramus of the mandible may show correlation of BMD with
      skeletal sites, the areas of the jaws where implants may be placed do not.
      Therefore BMD of the skeletal sites could not be used to predict BMD of the jaws.
      The BMD of the jaws as measured by DXA showed no relationship with either years
      edentulous or cigarette smoking.

PMID- 17517058
TI  - Infection at titanium implants with or without a clinical diagnosis of
      inflammation.
AB  - OBJECTIVES: To assess the microbiota at implants diagnosed with peri-implantitis,
      implant mucositis, or being clinically healthy. MATERIAL AND METHODS: Clinical
      and microbiological data were collected from 213 subjects (mean age: 65.7+/-14)
      with 976 implants in function (mean: 10.8 years, SD+/-1.5). Forty species were
      identified by the checkerboard DNA-DNA hybridization method. RESULTS: Implant
      mean % plaque score was 41.8+/-32.4%. Periodontitis defined by bone loss was
      found in 44.9% of subjects. Implant mucositis was diagnosed in 59% and peri
      implantitis in 14.9% of all cases. Neisseria mucosa, Fusobacterium nucleatum sp.
      nucleatum, F. nucleatum sp. polymorphum, and Capnocytophaga sputigena dominated
      the implant sub-mucosal microbiota and the sub-gingival microbiota at tooth
      sites. Implant probing pocket depth at the implant site with the deepest probing
      depth was correlated with levels of Eikenella corrodens (r=0.16, P<0.05), the
      levels of F. nucleatum sp. vincentii (r=0.15, P<0.05), Porphyromonas gingivalis
      (r=0.14, P<0.05), and Micromonas micros (r=0.17, P=0.01). E. corrodens was found
      in higher levels at implants with mucositis compared with implant health
      (P<0.05). Subjects who lost teeth due to periodontitis had higher yields of F.
      nucleatum sp. vincentii (P<0.02) and N. mucosa (P<0.05). Independent of implant
      status subjects with teeth had higher levels of P. gingivalis (P<0.05), and
      Leptotrichia buccalis (P<0.05). CONCLUSIONS: At implant sites studied, few
      bacteria differed by whether subjects were dentate or not or by implant status.

PMID- 17517059
TI  - Histological evaluation of oral implants inserted with different surgical
      techniques into the trabecular bone of goats.
AB  - OBJECTIVE: The aim of this study was to investigate the influence of implant
      surface topography and surgical technique on bone response. MATERIAL AND METHODS:
      For the experiment, 48 screw-designed implants were used with two different
      surface finishes, i.e. machined and 'blasted, etched'. The implants were inserted
      into the left and right medial femoral condyle of eight goats using three
      different surgical approaches: press-fit (implant diameter=implant bed
      diamete(r), undersized (implant bed diameter<implant diameter) and osteotome.
      Each femoral condyle received three implants. After an implantation period of 12
      weeks, the implants were retrieved and prepared for histological and
      histomorphometrical evaluation (bone contact and bone mass). RESULTS: Light
      microscopy revealed that in general, the bone response to all implants was very
      similar. On the other hand, histomorphometry suggested that the bone-to-implant
      contact for the 'blasted, etched' implants inserted by an undersized technique
      was higher compared with machined implants and the other surgical approaches, but
      the observed differences were not significant. Bone mass measurements did not
      reveal the occurrence of clear differences between groups and surgical
      approaches. CONCLUSION: Supported by our findings, we conclude that implants
      provided with a 'blasted, etched' surface and installed in trabecular bone using
      an undersized preparation technique appear to support an enhanced bone-implant
      contact. The use of an osteotome technique did not lead to improved results.

PMID- 17517060
TI  - Randomized clinical trials in implant therapy: relationships among
      methodological, statistical, clinical, paratextual features and number of
      citations.
AB  - OBJECTIVES: The aim of the present study was to investigate the relationships
      among reported methodological, statistical, clinical and paratextual variables of
      randomized clinical trials (RCTs) in implant therapy, and their influence on
      subsequent research. MATERIALS AND METHODS: The material consisted of the RCTs in
      implant therapy published through the end of the year 2000. Methodological,
      statistical, clinical and paratextual features of the articles were assessed and
      recorded. The perceived clinical relevance was subjectively evaluated by an
      experienced clinician on anonymous abstracts. The impact on research was measured
      by the number of citations found in the Science Citation Index. A new statistical
      technique (Structural learning of Bayesian Networks) was used to assess the
      relationships among the considered variables. RESULTS: Descriptive statistics
      revealed that the reported methodology and statistics of RCTs in implant therapy
      were defective. Follow-up of the studies was generally short. The perceived
      clinical relevance appeared to be associated with the objectives of the studies
      and with the number of published images in the original articles. The impact on
      research was related to the nationality of the involved institutions and to the
      number of published images. CONCLUSIONS: RCTs in implant therapy (until 2000)
      show important methodological and statistical flaws and may not be appropriate
      for guiding clinicians in their practice. The methodological and statistical
      quality of the studies did not appear to affect their impact on practice and
      research. Bayesian Networks suggest new and unexpected relationships among the
      methodological, statistical, clinical and paratextual features of RCTs.

PMID- 17517061
TI  - Histodynamics of bone tissue formation around immediately loaded cylindrical
      implants in the rabbit.
AB  - OBJECTIVES: The local mechanical environment influences early peri-implant tissue
      formation. It is still unclear whether immediate loading limits or promotes peri
      implant osteogenesis and which mechanical parameters are important herein. The
      present study evaluated the influence of well-controlled mechanical stimuli on
      the tissue response around immediately loaded cylindrical turned titanium
      implants at two different observation periods. MATERIAL AND METHODS: A repeated
      sampling bone chamber, consisting of dual-structure perforated hollow cylinders
      with a cylindrical implant, was installed in the tibia of 14 rabbits and used to
      conduct three displacement-controlled immediate loading experiments: (i) 30
      microm - 400 cycles/day - 1 Hz frequency - 2 x/week - 6 weeks; (ii) 30 microm -
      400 cycles/day - 1 Hz - 2 x/week - 6 weeks, followed by another 6 weeks with a 50
      microm - 800 cycles/day - 1 Hz - 2 x/week loading protocol; and (iii) 0 microm
      implant displacement for 12 weeks. A linear mixed model and logistic mixed model
      with alpha=5% were conducted on the data set. RESULTS: The tissue area fraction
      was significantly the highest after 12 weeks of loading. The bone area fraction
      was significantly different between all three loading conditions, with the
      highest values for the 12-week loading experiment. Twelve-week stimulation
      resulted in a significantly higher mineralized bone fraction than 6 weeks.
      Loading did have a significantly positive effect on the mineralized bone
      fraction. The incidence of osteoid-to-implant and bone-to-implant contact
      increased significantly when loading the implant for 12 weeks. CONCLUSION:
      Immediate loading had a positive effect on the tissue differentiation and bone
      formation around cylindrical turned titanium implants. Controlled implant micro
      motion up to 50 microm had a positive effect on the bone formation at its
      interface.

PMID- 17517062
TI  - Helicobacter pylori environmental interactions: effect of acidic conditions on H.
      pylori-induced gastric mucosal interleukin-8 production.
AB  - To explore the interactions between the host, environment and bacterium
      responsible for the different manifestations of Helicobacter pylori infection, we
      examined the effect of acidic conditions on H. pylori-induced interleukin (IL)-8
      expression. AGS gastric epithelial cells were exposed to acidic pH and infected
      with H. pylori[wild-type strain, its isogenic cag pathogenicity island (PAI)
      mutant or its oipA mutant]. Exposure of AGS cells to acidic pH alone did not
      enhance IL-8 production. However, following exposure to acidic conditions, H.
      pylori infection resulted in marked enhancement of IL-8 production which was
      independent of the presence of the cag PAI and OipA, indicating that H. pylori
      and acidic conditions act synergistically to induce gastric mucosal IL-8
      production. In neutral pH environments H. pylori-induced IL-8 induction involved
      the NF-kappaB pathways, the extracellular signal-regulated kinase (ERK)-->c-Fos/c
      Jun-->activating protein (AP-1) pathways, JNK-->c-Jun-->AP-1 pathways and the p38
      pathways. At acidic pH H. pylori-induced augmentation of IL-8 production involved
      markedly upregulated the NF-kappaB pathways and the ERK-->c-Fos-->AP-1 pathways.
      In contrast, activation of the JNK-->c-Jun-->AP-1 pathways and p38 pathways were
      pH independent. These results might explain the clinical studies in which
      patients with duodenal ulcers had higher levels of IL-8 in the antral gastric
      mucosa than patients with simple H. pylori gastritis.

PMID- 17517063
TI  - Lipoprotein lipase mediates hepatitis C virus (HCV) cell entry and inhibits HCV
      infection.
AB  - The host-virus interactions leading to cell infection with hepatitis C virus
      (HCV) are not fully understood. The tetraspanin CD-81 and human scavenger
      receptor SR-BI/Cla1 are major receptors mediating virus cell entry. However, HCV
      in patients' sera is associated with lipoproteins and infectious potential of the
      virus depends on lipoproteins associated to virus particles. We show here that
      lipoprotein lipase (LPL), targeting triglyceride-rich lipoproteins (TRL) to the
      liver, mediates binding and internalization of HCV to different types of cells,
      acting as a bridge between virus-associated lipoproteins and cell surface heparan
      sulfate proteoglycans (HSPG). The dimeric structure and catalytic activity of LPL
      are required for LPL-mediated HCV uptake to cells. Unexpectedly, exogenous LPL
      significantly inhibits HCVcc infection in vitro. This effect is prevented by anti
      LPL antibodies and by tetrahydrolipstatin (THL) a specific inhibitor of LPL
      enzymatic activity. In addition, we show that antibodies directed to
      apolipoprotein B (ApoB)-containing lipoproteins efficiently inhibits HCVcc
      infection. Our findings suggest that LPL mediates HCV cell entry by a mechanism
      similar to hepatic clearance of TRL from the circulation, promoting a non
      productive virus uptake. These data provide new insight into mechanisms of HCV
      cell entry and suggest that LPL could modulate HCV infectivity in vivo.

PMID- 17517064
TI  - A Francisella tularensis pathogenicity island protein essential for bacterial
      proliferation within the host cell cytosol.
AB  - Francisella tularensis is an intracellular bacterial pathogen, and is a category
      A bioterrorism agent. Within quiescent human macrophages, the F. tularensis
      pathogenicity island (FPI) is essential for bacterial growth within quiescent
      macrophages. The F. tularensis-containing phagosome matures to a late endosome
      like stage that does not fuse to lysosomes for 1-8 h, followed by gradual
      bacterial escape into the macrophage cytosol. Here we show that the FPI protein
      IglD is essential for intracellular replication in primary human monocyte-derived
      macrophages (hMDMs). While the parental strain replicates robustly in pulmonary,
      hepatic and splenic tissues of BALB/c mice associated with severe
      immunopathologies, the isogenic iglD mutant is severely defective. Within hMDMs,
      the iglD mutant-containing phagosomes mature to either a late endosome-like
      phagosome, similar to the parental strain, or to a phagolysosome, similar to
      phagosomes harbouring the iglC mutant control. Despite heterogeneity and
      alterations in phagosome biogenesis, the iglD mutant bacteria escape into the
      cytosol faster than the parental strain within hMDMs and pulmonary cells of
      BALB/c mice. Co-infections of hMDMs with the wild-type strain and the iglD
      mutant, or super-infection of iglD mutant-infected hMDMs with the wild-type
      strain show that the mutant strain replicates robustly within the cytosol of
      hMDMs coinhabited by the wild strain. However, when the wild-type strain-infected
      hMDMs are super-infected by the iglD mutant, the mutant fails to replicate in the
      cytosol of communal macrophages. This is the first demonstration of a F.
      tularensis novel protein essential for proliferation in the macrophage cytosol.
      Our data indicate that F. tularensis transduces signals to the macrophage cytosol
      to remodel it into a proliferative niche, and IglD is essential for transduction
      of these signals.

PMID- 17517065
TI  - Staphylococcal enterotoxin induces emesis through increasing serotonin release in
      intestine and it is downregulated by cannabinoid receptor 1.
AB  - Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus are the most
      recognizable bacterial superantigenic toxins causing food poisoning in humans
      throughout the world. However, it remains unclear how SEs induce emesis and its
      emetic signal pathway. We investigated a mechanism of SEA-induced emesis using a
      small emetic animal model, house musk shrew. SEA-induced emesis in the animals
      was inhibited by a 5-hydroxytryptamine (5-HT) synthesis inhibitor and a 5-HT(3)
      receptor antagonist. SEA could increase 5-HT release in the small intestine. Pre
      treatment with 5,7-dihydroxytryptamine (5,7-DHT) markedly inhibited SEA-induced
      emesis. SEA-induced emesis was also abolished by surgical vagotomy. Furthermore,
      cannabinoid (CB) receptor agonists inhibited SEA-induced emesis, and the action
      was reversed by a CB1 antagonist. Both 5-HT release and CB1 receptor expression
      were found in the mucosal and myenteric plexus of the intestine. Moreover, a CB1
      receptor agonist significantly decreased the 5-HT release in the intestine. These
      results demonstrate that SEA induces 5-HT release in intestine, rather than in
      brain, and that the 5-HT(3) receptors on vagal afferent neurons are essential for
      SEA-stimulated emesis. In addition, SEA-induced emesis is downregulated by the CB
      system through decreasing 5-HT release in intestine.

PMID- 17517066
TI  - Rosiglitazone RECORD study: glucose control outcomes at 18 months.
AB  - AIMS: To compare glucose control over 18 months between rosiglitazone oral
      combination therapy and combination metformin and sulphonylurea in people with
      Type 2 diabetes. METHODS: RECORD, a multicentre, parallel-group study of
      cardiovascular outcomes, enrolled people with an HbA(1c) of 7.1-9.0% on maximum
      doses of metformin or sulphonylurea. If on metformin they were randomized to add
      on rosiglitazone or sulphonylurea (open label) and if on sulphonylurea to
      rosiglitazone or metformin. HbA(1c) was managed to < or = 7.0% by dose titration.
      A prospectively defined analysis of glycaemic control on the first 1122
      participants is reported here, with a primary outcome assessed against a non
      inferiority margin for HbA(1c) of 0.4%. RESULTS: At 18 months, HbA(1c) reduction
      on background metformin was similar with rosiglitazone and sulphonylurea
      [difference 0.07 (95% CI -0.09, 0.23)%], as was the change when rosiglitazone or
      metformin was added to sulphonylurea [0.06 (-0.09, 0.20)%]. At 6 months, the
      effect on HbA(1c) was greater with add-on sulphonylurea, but was similar whether
      sulphonylurea was added to rosiglitazone or metformin. Differences in fasting
      plasma glucose were not statistically significant at 18 months [rosiglitazone vs.
      sulphonylurea -0.36 (-0.74, 0.02) mmol/l, rosiglitazone vs. metformin -0.34 (
      0.73, 0.05) mmol/l]. Increased homeostasis model assessment insulin sensitivity
      and reduced C-reactive protein were greater with rosiglitazone than metformin or
      sulphonylurea (all P < or = 0.001). Body weight was significantly increased with
      rosiglitazone compared with sulphonylurea [difference 1.2 (0.4, 2.0) kg, P =
      0.003] and metformin [difference 4.3 (3.6, 5.1) kg, P < 0.001]. CONCLUSIONS: In
      people with diabetes, rosiglitazone in combination with metformin or
      sulphonylurea was demonstrated to be non-inferior to the standard combination of
      metformin + sulphonylurea in lowering HbA(1c) over 18 months, and produces
      greater improvements in C-reactive protein and basal insulin sensitivity but is
      also associated with greater weight gain.

PMID- 17517068
TI  - Differential distribution of the endoplasmic reticulum network in filamentous
      fungi.
AB  - Filamentous fungi are composed of hyphal compartments divided by septa, which
      communicate via septal pores. Apical compartments can elongate to over 100 microm
      without septum formation and possess a polarized distribution of organelles. In
      Aspergillus, subapical compartments are arrested in interphase but can reinitiate
      mitosis and growth by branching. Recent reports using green fluorescent protein
      (GFP) technology have demonstrated the highly differentiated localization of the
      endoplasmic reticulum (ER) network in various regions of the hyphae: the gradient
      distribution from the apical region, the localization along the septum,
      differential distributions in adjacent compartments, and the dynamic
      morphological change during septum formation. In this review the spatial
      regulation of the ER network in multicellular filamentous fungi is discussed.

PMID- 17517067
TI  - Rac1, RhoA, and Cdc42 participate in HeLa cell invasion by group B streptococcus.
AB  - The group B streptococcus (GBS) is an important human pathogen with the ability
      to cause invasive disease. To do so, the bacteria must invade host cells. It has
      been well documented that GBS are able to invade a variety of nonphagocytic host
      cell types, and this process is thought to involve a number of pathogen-host cell
      interactions. While some of the molecular aspects of the GBS-host cell invasion
      process have been characterized, many events still remain unclear. The objective
      of this investigation was to evaluate the role of the Rho-family GTPases Rac,
      Rho, and Cdc42 in GBS invasion into epithelial cells. The epithelial cell
      invasion process was modeled using HeLa 229 cell culture. Treatment of HeLa cells
      with 10 microM compactin, a pan-GTPase inhibitor, abolished GBS internalization,
      suggesting that GTPases are involved in the GBS invasion process. The addition of
      Toxin B or exoenzyme C3 to HeLa cells before GBS infection reduced invasion by
      50%, further suggesting that the Rho-family GTPases are involved in GBS entry.
      Examining invasion of GBS into HeLa cells with altered genetic backgrounds was
      used to confirm these findings; GBS invasion into HeLa cells transiently
      transfected with dominant negative Rac1, Cdc42, or RhoA reduced invasion by 75%,
      51%, and 42%, respectively. Results of this study suggest that the Rho-family
      GTPases are required for efficient invasion of HeLa cells by GBS.

PMID- 17517069
TI  - Importance of chemical structure on the development of hydrocarbon catabolism in
      soil.
AB  - A soil was amended with (14)C-analogues of naphthalene, phenanthrene, pyrene,
      B[a]P or hexadecane at 50 mg kg(-1) and the development of catabolic activity was
      assessed by determining the rate and extent of (14)CO(2) evolution at time points
      over 180 days. The catabolic potential of the soil was
      hexadecane>naphthalene>phenanthrene>pyrene>B[a]P, determined by the decrease in
      lag time (as defined by the time taken for 5%(14)CO(2) to be evolved from the
      minerialization of the (14)C-labeled hydrocarbons). The results clearly showed
      the difference between constitutive and inducible biodegradation systems. The 0
      day time point showed that hexadecane minerialization was rapid and immediate,
      with a 45.4 +/- 0.6% mineralization extent, compared with pyrene minerialization
      at 1.0 +/- 0.1%. However, catabolism for pyrene developed over time and after a
      95 days soil-pyrene contact time, mineralization extent was found to be 63.1 +/-
      7.8%. Strong regression was found (r(2)>0.99) between the maximum rates of
      mineralization and the partioning coefficient between the mineralized
      hydrocarbons, which may indicate linearity in the system.

PMID- 17517070
TI  - Evaluation of the effects of combination therapy with branched-chain amino acid
      and zinc supplements on nitrogen metabolism in liver cirrhosis.
AB  - AIM: Disorders of protein metabolism in liver cirrhosis can affect prognosis or
      cause complications. Treatment with branched-chain amino acid (BCAA) and zinc
      supplements has been shown to be effective against abnormal nitrogen metabolism
      in liver cirrhosis. There are, however, few studies on the effects of combining
      these supplements. In this study, the effect of combining BCAA and zinc treatment
      in cirrhosis was investigated. METHODS: Forty patients with liver cirrhosis who
      had blood albumin levels of 3.5 g/dL or less and blood zinc levels of 70 mug/dL
      or less were randomized to receive either BCAA alone or a combination of BCAA and
      zinc supplements. Blood albumin, the Fischer ratio, and ammonia levels were
      compared over 5-6 months of treatment. RESULTS: In the combination group, the
      post/pre treatment change ratio in blood ammonia levels decreased significantly
      (0.87 +/- 0.26 vs. 1.22 +/- 0.38, P = 0.0033), and the change ratio in the
      Fischer ratio increased significantly (1.22 +/- 0.29 vs. 1.08 +/- 0.16, P =
      0.0165) in comparison with the BCAA monotherapy group. The change ratio in blood
      albumin levels showed no significant difference between the groups (1.01 +/- 0.07
      vs. 1.03 +/- 0.08, P = 0.4646). CONCLUSIONS: More improvement in disorders of
      nitrogen metabolism in liver cirrhosis occurred after administration of BCAA with
      zinc than after BCAA alone over 5-6 months of treatment. Further investigation is
      necessary to determine mechanisms of the action and longer-term clinical
      efficacy.

PMID- 17517071
TI  - Intracellular balance of oxidative stress and cytoprotective molecules in damaged
      interlobular bile ducts in autoimmune hepatitis and primary biliary cirrhosis: In
      situ detection of 8-hydroxydeoxyguanosine and glutathione-S-transferase-pi.
AB  - AIM: Bile duct injury has been thought to be absent in autoimmune hepatitis
      (AIH), but recent studies have indicated that AIH patients do have bile duct
      injury. In this study, the intracellular balance of oxidative stress and
      cytoprotection in biliary epithelial cells was investigated to clarify the
      pathogenesis of bile duct injury in AIH. METHODS: The intracellular status of
      oxidative DNA damage caused by oxidative stress and glutathione, an endogenous
      cytoprotective molecule, were examined in patients with AIH, primary biliary
      cirrhosis (PBC), and normal controls by immunostaining of 8-hydroxydeoxyguanosine
      (8-OHdG) and glutathione-S-transferase-pi. RESULTS: Immunohistochemically, 8-OHdG
      expression was detected as abundantly in the damaged bile ducts of AIH patients
      as in PBC patients. Moreover, in AIH, 8-OHdG expression was detected in damaged
      bile ducts more than in undamaged bile ducts. Glutathione-S-transferase-pi
      expression was relatively preserved in the damaged bile ducts of AIH patients
      compared to PBC patients, reflecting preservation of intracellular glutathione.
      CONCLUSIONS: In AIH, oxidative stress and DNA damage may be involved in the
      pathogenesis of bile duct injury in a manner similar to that found in PBC.
      However, relatively preserved intracellular glutathione may play a key role in
      preventing progressive bile duct loss following bile duct injury in AIH.

PMID- 17517073
TI  - Does l-carnitine have any effect on cold preservation injury of non-fatty liver
      in the University of Wisconsin solution?
AB  - AIM: To evaluate the protective effect of l-carnitine on liver tissue preserved
      in University of Wisconsin (UW) solution. METHODS: Twenty Wistar Albino rats were
      divided into two groups, a control (UW) group and a UW plus l-carnitine group.
      Retrieved liver grafts were preserved in UW and UW plus l-carnitine solutions at
      +4 degrees C. Preservation solution samples were assessed at 2, 24, 36, and 48 h
      to measure alanine aminotransferase and acid phosphatase activity. Tissue injury
      was scored on paraffin sections. RESULTS: No micro or macrovacuolar fat droplets
      were observed in the tissue slices. l-Carnitine effectively decreased enzyme
      release when added to UW solution (P < 0.05). CONCLUSION: In addition to fatty
      liver, l-carnitine might be a metabolic adjunct in preservation solutions for non
      fatty liver within UW solution.

PMID- 17517072
TI  - Protective effect of interferon-alpha on the DNA- and RNA-degrading pathway in
      anti-Fas-antibody induced apoptosis.
AB  - AIM: Fas membrane-associated polypeptide antigen is a receptor molecule
      responsible for apoptosis-mediated signals. In animal models of acute viral
      hepatitis, apoptosis of hepatocytes is mediated by Fas-death receptors;
      therefore, the aim of this study was to evaluate the effect of interferon (IFN)
      alpha on apoptotic markers and nuclease activity against different coding and non
      coding single and double stranded RNAs during Fas-induced liver apoptosis.
      METHODS: An in vivo experiment was performed with simultaneous administration of
      anti-Fas (CD95) antibodies and IFN-alpha, and an in vitro experiment was
      performed in hepatocyte cultures treated with anti-Fas antibodies and IFN-alpha.
      RESULTS: Detection of apoptosis using Annexin V-FITC/propidium iodide, Bcl-2 and
      Bax expression in hepatocyte cultures confirmed the appearance of early apoptotic
      events and progression toward late apoptosis after anti-Fas antibody treatment.
      IFN-alpha had a tendency to retard the apoptosis process in Fas-induced apoptosis
      by increasing the number of viable cells and decreasing the number of cells in
      late apoptosis, by increasing the percentage of Bcl-2 positive cells, by
      decreasing the percentage of Bax positive cells, and by decreasing the nuclease
      activity compared to the anti-Fas antibody treated group. Total DNA and RNA
      concentration was much reduced in the Fas group and DNA fragmentation assay
      provided evidence for increased DNA degradation. Enhanced nuclease activity
      against DNA, rRNA, poly(A), poly(C), poly(U), poly(I:C), and poly(A:U) was
      manifested in the anti-Fas antibody treated group, except for the inhibitory
      bound alkaline RNase. CONCLUSIONS: The results demonstrate that the RNA-degrading
      pathway in Fas-induced apoptosis can accelerate the liberation of the latent
      enzyme from the inhibitor complex. IFN-alpha prevented enormous, Fas-ligand
      induced degradation of all the substrates used in this experimental study, most
      probably due to similarities in the signal transduction pathways. Investigations
      of death receptor-induced apoptosis may lead to novel treatment combinations for
      patients with acute or chronic liver diseases.

PMID- 17517074
TI  - Immunopathogenesis of hepatitis C virus infection and hepatic fibrosis: New
      insights into antifibrotic therapy in chronic hepatitis C.
AB  - Fibrosis and cirrhosis represent the consequences of a sustained wound-healing
      response to chronic liver injury of any cause. Chronic hepatitis C virus (HCV)
      has emerged as a leading cause of cirrhosis in the USA and throughout the world.
      HCV may induce fibrogenesis directly by hepatic stellate cell activation or
      indirectly by promoting oxidative stress and apoptosis of infected cells. The
      ultimate result of chronic HCV injury is the accumulation of extracellular matrix
      with high density type I collagen within the subendothelial space of Disse,
      culminating in cirrhosis with hepatocellular dysfunction. The treatment of
      hepatitis C with the combination of pegylated interferon and ribavirin is still
      both problematic and costly, has suboptimal efficacy, serious side effects and a
      high level of intolerance, and is contraindicated in many patients. Hence, new
      approaches have assumed greater importance, for which there is an urgent need.
      The sustained progress in understanding the pathophysiology of hepatic fibrosis
      in the past two decades has increased the possibility of developing drugs
      specifically targeting the fibrogenic process. Future efforts should identify
      genetic markers associated with fibrosis risk in order to tailor the treatment of
      HCV infection based on genetically regulated pathways of injury and/or fibrosis.
      Such advances will expand the arsenal to overcome liver fibrosis, particularly in
      patients with hepatic diseases who have limited treatment options, such as those
      patients with chronic hepatitis C who have a high risk of fibrosis progression
      and recurrent HCV disease after liver transplantation.

PMID- 17517075
TI  - Effect of a late evening snack on outpatients with liver cirrhosis.
AB  - AIMS: We have reported that one-week administration of a late evening snack (LES)
      improved not only malnutrition but also glucose intolerance in hospitalized
      patients with liver cirrhosis. Thus, we investigated whether long-term LES
      administration to outpatients for 3 months could reproduce the results obtained
      from hospitalized patients, especially improved glucose intolerance. If this
      treatment aggravated glucose intolerance, we tried to find any marker predicting
      this aggravation before the treatment. METHODS: Outpatients were prescribed one
      pack of oral supplementation of a branched-chain amino acid (BCAA)-enriched
      nutrient, Aminoleban EN (210 kCal) as a LES without dietician supervision. Both
      before LES administration and after 3 months, glucose tolerance and liver
      function were examined using a 75 g oral glucose tolerance test (OGTT),
      biochemical parameters in blood and the relationship between glucose tolerance
      (area under the curve (AUC)) and the following serum markers. RESULTS: Branched
      chain amino acid/tyrosine ratio (BTR), the number of red blood cells (RBC), and
      hematocrit (Ht) significantly increased, with significant reduction of blood
      NH(3) level in patients with a blood glucose level less than 200 mg/dL 2 h after
      75 g OGTT. However, the increase of AUC was seen after 3 months of LES
      administration in patients who had blood glucose higher than 200 mg/dL 2 h after
      75 g OGTT. AUC weakly correlated positively with serum 7S collagen and negatively
      with choline esterase (ChE) and albumin (Alb). CONCLUSION: 75 g OGTT is a useful
      marker to predict the worst outcome and avoid the adverse effect of LES treatment
      in liver cirrhosis patients if performed without adequate nutrient conduct by a
      dietician.

PMID- 17517076
TI  - Clinical and pathological features of a prolonged type of acute intrahepatic
      cholestasis.
AB  - AIM: We examined the clinical and pathological features of drug-induced acute
      intrahepatic cholestasis (AIC) to elucidate the pathogenesis of prolonged cases.
      METHODS: Twenty-six cases of drug-induced AIC were divided into prolonged and non
      prolonged groups. Serum bilirubin levels and other biochemical data were compared
      between the two groups. Biopsy liver specimens were examined by light and
      electron microscopy. The localization of multidrug resistance protein 2 (MRP2)
      was immunohistochemically assessed by the Envision technique. RESULTS: The
      causative drugs of four prolonged cases were found to be tiopronin,
      chlorpromazine and diclofenac. Two of the patients either died or underwent liver
      transplantation. The maximal total bilirubin levels (35.2 +/-> 13.8 mg/dL) were
      significantly higher and a half-life of total bilirubin (78.8 +/-> 69.6 days) was
      markedly longer in the prolonged cases, in comparison to the non-prolonged cases
      (16.8 +/-> 8.1 mg/dL, 22.1 +/-> 12.7 days, respectively). The liverbiopsy
      specimens revealed canalicular cholestasis and a slight degree of lobular
      inflammation. In the prolonged cases, liver cell injury and cholestasis was
      marked, and the interlobular bile ducts disappeared in the portal triads. The
      reaction products of MRP2, recognized on the bile canaliculi in a control liver,
      were weakened and found in the pericanalicular vesicles in AIC. CONCLUSION: These
      results indicated disturbances in the canalicular bilirubin transport through
      MRP2 in the prolonged cases, resulting from severe cholestasis, liver cell injury
      and vanishing bile ducts. The histological findings of the liver at the acute
      icteric phase may be important to understand the pathogenesis and to predict the
      prognosis in AIC.

PMID- 17517077
TI  - Genetic background of Japanese patients with adult-onset storage diseases in the
      liver.
AB  - In contrast to primary lysosomal diseases in young subjects, adult-onset liver
      storage disorders may be explained by non-lysosomal genetic defects. The aim of
      the present review is to summarize the genetic backgrounds of Japanese patients
      with hemochromatosis of unknown etiology, Wilson disease of primary copper
      toxicosis, and the black liver of Dubin-Johnson syndrome. Three patients with
      middle-age onset hemochromatosis were homozygous for mutations of HJV and two
      patients were homozygous for mutations of TFR2. Minor genes other than HJV and
      TFR2 might be involved in Japanese patients. Five of the six patients with Wilson
      disease were compound heterozygous, while the remaining patient was heterozygous
      for the mutation in ATP7B responsible for copper toxicosis. Involvement of MURR1
      was not proved in the heterozygote of ATP7B. Because of ferroxidase
      deficiency,most patients had secondary lysosomes shared by cuprothioneins and
      iron complex. Six patients with Dubin-Johnson syndrome were homozygous or
      compound heterozygous for mutant MRP2. Despite complex metabolic disorders, the
      syndrome had a single genetic background. Thus, most patients with adult-onset
      lysosomal proliferation in the liver had genetic defects in non-lysosomal
      organelles, named the secondary lysosomal diseases. The proliferating lysosomes
      in these conditions seemed to be heterogeneous in their matrices.

PMID- 17517078
TI  - Downregulated expression of metallothionein and its clinicopathological
      significance in hepatocellular carcinoma.
AB  - AIM: Metallothionein (MT) protein is related to different stages of development
      and progression of various tumors in humans. The aim of the present study was to
      investigate expression and localization of MT and their association with
      clinicopathological characteristics in hepatocellular carcinoma (HCC). METHODS:
      Histological specimens of 400 HCC with corresponding non-cancerous liver tissues
      were stained for MT (E9), P53 and Ki-67 by immunohistochemical staining using
      tissue microarrays. RNA expression of MT-1X and MT-2A isoforms was determined by
      real-time reverse transcription-polymerase chain reaction in a set of independent
      samples of 161 HCC. RESULTS: Downregulated expression of MT at both mRNA and
      protein levels was detected in HCC, compared with non-cancerous liver tissues.
      The frequencies of MT positivity were significantly lower in cases with positive
      hepatitis B surface antigen than in those with negative hepatitis B
      surfaceantigen (P = 0.042). The positive rate of MT expression was more frequent
      in tumors </=2 cm than in tumors >2 cm in diameter (P = 0.007). There was a
      tendency for MT expression to decrease with the progression of histological
      grade. Mainly nuclear expression of MT correlated with poorly differentiated HCC.
      No statistical correlation was found between P53, Ki-67 and MT expression.
      CONCLUSIONS: Downregulated expression of MT in HCC may play a role in
      hepatocarcinogenesis and be a marker of hepatocellular differentiation. Hepatitis
      B virus infection may be correlated to downregulated expression of MT. The mainly
      nuclear MT immunostaining may reflect an aggressive behavior in poorly
      differentiated HCC.

PMID- 17517079
TI  - Delirium in elderly general medical inpatients: a prospective study.
AB  - BACKGROUND: More than 49% of all US hospital days are spent caring for patients
      with delirium. There are few Australian data on this important condition. The aim
      of the study was to determine the prevalence and incidence of delirium in older
      medical inpatients in a metropolitan teaching hospital, the incidence of known
      risk factors and current practice in identifying and managing patients at risk of
      this condition. METHODS: Patients aged 65 years or more, and admitted to a
      general medical unit, were eligible for study inclusion. Participants were
      screened with an Abbreviated Mental Test Score (AMTS) and chart review. Confusion
      Assessment Method was used to diagnose delirium if confusion was documented or
      AMTS < 8. Barthel Index (BI), demographics, delirium risk factors and management
      were recorded. RESULTS: Prevalent delirium was diagnosed in 19 of 104 (18%) and
      incident delirium in 2 of 85 (2%) participants. Pre-existing cognitive impairment
      and admission AMTS < 8 were strongly associated with prevalent delirium (P-values
      < 0.01). Age > 80 years, Barthel Index < or = 50, use of high-risk medications
      and electrolyte disturbance were also associated with prevalent delirium.
      Prevalent delirium was not recognized by the treating unit in 4 of 19 cases
      (21%). Five of 104 (4.8%) of participants had a formal cognitive assessment on
      admission. One of 19 patients (5.3%) with prevalent delirium had an orientation
      device in their room. CONCLUSION: Pre-existing cognitive impairment and admission
      AMTS are strong predictors of delirium. Despite this, formal cognitive assessment
      is not routinely carried out in elderly medical patients. Recognition of delirium
      may be improved by routine cognitive assessment in elderly medical patients.

PMID- 17517080
TI  - Vitamin D deficiency in a multinational refugee population.
AB  - BACKGROUND: Populations with increased skin pigmentation who have migrated to
      countries of high latitude are at increased risk of low vitamin D. This study
      aimed to determine the prevalence of low vitamin D among the refugee population
      arriving in New Zealand. METHODS: An audit of all refugees arriving at the
      national refugee resettlement centre from May 2004 to May 2005 was carried out.
      Serum 25-hydroxyvitamin D3 levels were measured and defined as normal (50-150
      nmol/L) or low, with low subdivided into insufficient (25 to <50 nmol/L) and
      deficient (<25 nmol/L). Whether vitamin D status varied with age and sex was
      determined. RESULTS: Vitamin D was measured in 869 (99%) of the refugees and was
      low in 470 (54%, 95% confidence interval (CI) 51-57%). It was insufficient in 323
      (37%, 95%CI 34-41%) and deficient in 147 (17%, 95%CI 15-20%). Female sex was
      associated with at least a 10 times increased risk of vitamin D deficiency
      (relative ratio 13.93, 95%CI 10.15-17.96). Women aged between 17 and 45 years and
      men aged 46 years and more were at greatest risk. CONCLUSION: Poor vitamin D
      status is prevalent among refugees arriving in New Zealand. Women, particularly
      those of child-bearing age are at greatest risk. Screening and ongoing
      surveillance for vitamin D deficiency should be considered for all recent refugee
      immigrants to New Zealand.

PMID- 17517081
TI  - Psychological morbidity and burnout in palliative care doctors in Western
      Australia.
AB  - BACKGROUND: Medicine and particularly palliative care are considered to be
      stressful professions, with risks of psychological morbidity and burnout. There
      is little published work quantitatively documenting their prevalence among
      medical practitioners practising in palliative care. METHODS: Three
      questionnaires, including the General Health Questionnaire (GHQ-12) and the
      Maslach Burnout Inventory, were sent to palliative care practitioners in Western
      Australia. RESULTS: Forty-one of 43 (95%) practitioners completed the
      questionnaires. The mean score on the GHQ-12 was 1.9 (range 0-8), with 11 (27%)
      scoring 4 or more. On the Maslach Burnout Inventory, mean scores on the emotional
      exhaustion (EE, mean 17.5, range 1-47) and depersonalization subscales (DP, 4.5,
      0-24) fell within the low range, with scores for personal accomplishment (39, 32
      46) falling within the average range. Ten respondents (24%) scored high on either
      the EE subscale or the DP subscale, meeting criteria for burnout. GHQ-12 scores
      were associated with hours of work per week in palliative care (P = 0.004). The
      EE (P = 0.024) and DP (P = 0.006) components of burnout were associated with
      years of work in palliative care. Specialist practitioners were more likely to
      score in the high category for GHQ-12 (odds ratio = 4.8, P = 0.036) and EE (odds
      ratio = 8.33, P = 0.031). GHQ (P = 0.038) and DP (P = 0.006) scores were higher
      in those working in tertiary institutions, with tertiary practitioners more
      likely to be in the high EE category (odds ratio = 7.5, P = 0.034). CONCLUSION:
      Levels of psychiatric morbidity and burnout in palliative medicine are not higher
      than in other specialties.

PMID- 17517082
TI  - Prevalence of occult metastatic disease in patients undergoing 18F-FDG PET for
      primary diagnosis or staging of lung carcinoma and solitary pulmonary nodules.
AB  - BACKGROUND: Accurate staging of lung cancer is essential in determining the most
      appropriate management plan, as detection of occult metastasis can significantly
      alter management. AIMS: The aims of this study are to determine the prevalence of
      occult metastasis in patients undergoing 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F
      FDG) positron emission tomography (PET) for evaluation of suspected/proven lung
      carcinoma and correlate pre-PET TNM stage with prevalence of metastasis. METHODS:
      FDG-PET, which identified patients with metastasis on institutional database, was
      re-evaluated by a nuclear medicine physician blinded to clinical information. The
      confidence level of metastasis was scored on a 5-point scale, with a score of
      >/=4 considered positive. RESULTS: There were 67 of 645 (10%) patients identified
      with suspected occult metastasis on FDG-PET. Twelve patients scoring </=3 were
      excluded. Prevalence of occult metastasis was 10/156 (6%) in solitary pulmonary
      nodules (SPN); 22/319 (7%) and 23/170 (14%) in proven and suspected lung cancer,
      respectively. Positive predictive value of FDG-PET for metastasis was 8/10 (80%)
      in solitary pulmonary nodules, 14/20 (70%) and 17/21 (81%) in proven and
      suspected lung cancer, respectively. (18)F-FDG-avid lesions classified as false
      positives were patients with cholelithiasis, rib fractures and those with
      equivocal/negative bone scans or computed tomography on follow up. There was a
      higher incidence of true positive occult metastasis in patients in all stages of
      disease, particularly stage III disease. CONCLUSION: (18)F-FDG PET is predictive
      for occult metastatic disease in patients with solitary pulmonary nodules and
      proven or suspected lung cancer and is more likely to be present in all stages,
      particularly in stage III. PET findings should be actively pursued with
      correlative investigation to identify benign pathology in patients who remain
      candidates for curative treatment.

PMID- 17517083
TI  - Audit of pneumocystis pneumonia in patients seen by the Christchurch Hospital
      rheumatology service over a 5-year period.
AB  - AIM: The aim of the study was to review all cases of Pneumocystis carinii
      pneumonia (PCP) in patients seen by the Christchurch Hospital Rheumatology
      service over a 5-year period and to determine the annual incidence of PCP.
      METHODS: The Canterbury Health Laboratory database was searched for rheumatology
      patients testing positive for PCP from 31 December 2000 to 31 December 2005. The
      rheumatology database was then searched to identify patients receiving the same
      immunosuppressant medication as those who developed PCP to determine the annual
      incidence of PCP in this group. RESULTS: Four rheumatology patients were
      diagnosed with PCP during the 5-year period. Two were receiving oral methotrexate
      (MTX) for rheumatoid arthritis and two were receiving cyclophosphamide (CYC), one
      each for Wegener's granulomatosis and dermatomyositis. None of the four cases was
      receiving PCP chemoprophylaxis. Five hundred and forty-seven patients commenced
      MTX over the same 5-year period and 47 commenced CYC. Only 14 of 47 (29.7%) CYC
      treated patients received PCP prophylaxis. The annual incidence of PCP was 0.17%
      (95% confidence interval (CI) 0.02-0.63) and 5.33% (95%CI 0.65-19.24) in patients
      prescribed MTX and CYC, respectively. For the 33 patients receiving CYC without
      concomitant PCP prophylaxis the annual incidence was 9.50% (95%CI 1.15-34.33).
      CONCLUSION: In our study the annual incidence of PCP in patients taking MTX was
      low and would not support the use of routine PCP chemoprophylaxis. In patients
      receiving CYC without concomitant PCP chemoprophylaxis the annual incidence of
      PCP was higher although the number of cases was small. Given the high morbidity
      and mortality in this group, PCP chemoprophylaxis should be considered.

PMID- 17517084
TI  - Promoter hypomethylation of protease-activated receptor 2 associated with
      carcinogenesis in the stomach.
AB  - BACKGROUND AND AIM: Trypsin acting at protease-activated receptor 2 (PAR2)
      contributes to a progression of malignant tumors. An abnormal DNA methylation has
      been recognized as an important molecular mechanism for the genesis of various
      types of cancers. We attempted to clarify the relationship between the promoter
      methylation of PAR2 and gastric cancer. METHOD: We estimated the methylation of
      the PAR2 promoter in both antral non-cancerous mucosa and cancer lesions in 94
      patients with gastric cancer. We employed a methylation-specific PCR method.
      RESULTS: Regarding the methylation ratio (MR) of antral-non-cancerous mucosa, no
      significant difference was despite among gender, age and Helicobacter pylori
      infection status, whereas MR increased rising inflammation scores. The MR of
      cancer lesions was significantly lower than that of antral non-cancerous mucosa.
      This finding was not dependent on tumor staging, but also histological
      classification. In venous invasion, lymph node metastasis, or peritoneal
      dissemination negative cases, this significant lower MR was also seen.
      CONCLUSION: The promoter methylation of PAR2 seems to be increased with a
      progression of chronic inflammation and has an inhibitory effect on
      carcinogenesis of the stomach.

PMID- 17517085
TI  - Acute appendicitis in a chimpanzee (Pan troglodytes).
AB  - BACKGROUND: A 7-year old, female chimpanzee (Pan troglodytes) developed acute
      abdominal pain and anorexia. An irregular, mineral opacity was identified in the
      caudal right quadrant of the abdomen on radiographs and computed tomography scan,
      which appeared to be in the region of the cecal appendage. RESULTS AND
      CONCLUSIONS: A diagnosis of acute appendicitis was made based on clinical signs,
      abnormal haematology findings, and consultation with a human radiologist.
      Exploratory laparotomy was performed and the cecal appendage was removed. On
      histologic examination, the mucosal epithelium contained eosinophilic and
      neutrophilic inflammation. The inflammation extended through the tunica
      muscularis to the serosal surface and adjacent mesentery. The histologic findings
      were consistent with acute appendicitis in humans. The chimpanzee recovered well
      from surgery with immediate improvement in clinical signs and no post-operative
      complications.

PMID- 17517086
TI  - Alopecia areata in a rhesus monkey (Macaca mulatta).
AB  - BACKGROUND: A 14-year-old female rhesus monkey (Macaca mulatta) of Chinese origin
      has been suffering from alopecia universalis since childhood. METHODS: Recently,
      the health status of the animal was recorded comprehensively by detailed clinical
      examination including hematology and serology supplemented by histological and
      immunohistochemical investigations of skin biopsies and molecular biological
      techniques to clarify the causes of the persistent hair loss. RESULTS AND
      CONCLUSIONS: The hairless gene (hr) nonsense mutation was ruled out by polymerase
      chain reaction and by sequencing of the corresponding gene. Histological
      examinations revealed a prominent chronic lymphocytic perifolliculitis and
      folliculitis affecting anagen stage hair follicles as well as miniaturized hair
      follicles. Immunohistochemistry using the antibodies CD3, CD20 and CD4 confirmed
      the diagnosis of a T-cell-mediated autoimmune disease resembling alopecia areata
      universalis in humans.

PMID- 17517087
TI  - Preparation and characterization of new challenge stocks of SIVmac32H J5
      following rapid serial passage of virus in vivo.
AB  - BACKGROUND: A new challenge stock of the simian immunodeficiency virus SIVmacJ5
      has been produced following passage in vivo. METHODS: SIVmacJ5 3/92 (J5M), was
      passaged serially through cynomolgus macaques (Macaca fascicularis) by
      intravenous inoculation of infected spleen cells isolated and prepared 14 days
      post-infection. Two challenge stocks, SIVmacJ5 S61MLN and SIVmacJ5 S62spl, were
      prepared by culture of lymphoid tissue ex vivo. RESULTS: These virus stocks
      appeared better adapted for replication in M. fascicularis as demonstrated by a
      greater persistence of recoverable live virus from the periphery and increased
      pathology in lymphoid tissues 20 weeks post-challenge as detected by
      immunohistochemistry. Sequence analysis of the envelope gene from these stocks
      did not identify marked diversification of sequence as a result of this
      procedure. CONCLUSIONS: These stocks display more robust peripheral persistence
      and tissue pathology in cynomolgus macaques and should prove valuable analysing
      recombinant vaccines based upon SIVmacJ5 transgenes.

PMID- 17517088
TI  - Markers of cartilage and bone matrix metabolism differ between the sera of
      macaque and squirrel monkeys.
AB  - BACKGROUND: Nonhuman primates develop the characteristic lesions of
      osteoarthritis, making them attractive biomedical models for the study of
      environmental factors, such as diet, which may influence the progress of the
      condition. METHODS AND MATERIALS: We used ELISA assays of potential markers of
      osteoarthritis which were developed for use in humans to see if we could
      determined the presence of immunoreactivity in two nonhuman primate genera -
      Macaca (macaque monkeys) and Saimiri (squirrel monkeys). RESULTS: Inter-generic
      differences were significant for most markers. Three markers (bone alkaline
      phosphatase, hyaluronin and YKL-40) were outside the human range and two markers
      (laminin and C2C) did not yield useful results because they were off-scale high.
      CONCLUSION: Our results indicate that most of the ELISA assays designed for use
      with human serum can be used in nonhuman primates. The highly significant
      differences we observed between the sera of Macaca and Saimiri, suggest that
      further examination is warranted.

PMID- 17517089
TI  - External cephalic version of the term breech baboon (Papio sp.) fetus.
AB  - BACKGROUND: Breech presentation in baboons may be associated with head entrapment
      and stillbirth during vaginal delivery. For this reason, pregnant dams at our
      institution typically undergo cesarean delivery for known breech presentation,
      leading to problems with maternal-infant bonding and increased nursery
      utilization. METHODS: This paper describes a simple, non-invasive technique
      called external cephalic version (ECV) that effectively converts the baboon
      breech fetus into a cephalic presentation. RESULTS: ECV was successful in each of
      seven attempted cases, with the consistent development of contractions and
      vaginal bleeding leading to the delivery of a healthy liveborn infant within 72
      hours. CONCLUSIONS: ECV may offer a safe and effective alternative to cesarean
      section for delivery of the breech baboon fetus.

PMID- 17517090
TI  - Male-to-male differences in post-thaw motility of rhesus spermatozoa after
      cryopreservation of replicate ejaculates.
AB  - BACKGROUND: The efficiency of controlled propagation to produce rhesus monkeys of
      particular genotypes can be maximized by use of cryopreserved spermatozoa
      collected from specific males to inseminate appropriate females. But this assumes
      that semen from males with different genotypes can be cryopreserved with equal
      effectiveness. METHODS: To investigate whether spermatozoa from different Macaca
      mulatta males can be effectively cryopreserved when frozen under identical
      conditions, we collected and froze semen specimens from 13 adult, fertile males
      maintained at three primate research centers. RESULTS: Survival, based on post
      thaw motility normalized to the pre-freeze value, was assayed within 30 minutes
      after thawing; it varied from 50% to 70% but declined thereafter. To examine the
      response of semen from individual males, we collected and froze three to six
      ejaculates per male from each of seven males. CONCLUSIONS: In general, semen from
      a given male responded reproducibly to freezing, but there were significant
      differences among males. The cause of these differences among M. mulatta males in
      post-thaw sperm survival remains unidentified.

PMID- 17517091
TI  - Development, validation and application of a chemiluminescent immunoassay for the
      measurement of circulating chorionic gonadotropin levels in the laboratory
      macaque.
AB  - BACKGROUND: Methods for the measurement of chorionic gonadotropin for pregnancy
      detection in laboratory macaques chorionic gonadotropin (mCG) have been limited
      by the paucity of specific reagents. Current assays use reagents developed for
      human chorionic gonadotropin (hCG) assays and have been limited to radio- or
      enzyme-immuno assays. METHODS: This report describes an automated assay for mCG
      using reagents for hCG detection that has been adapted to the automated
      chemiluminescence platform of the Bayer ACS-180 autoanalyzer. RESULTS: This
      automated assay performs similarly to previous assays in terms of sensitivity and
      specificity but provides additional speed, reliability, and more easily
      accessible reagents compared with previous formats. CONCLUSIONS: When implemented
      broadly, this assay could provide standardization of mCG measurements for both
      research and colony management purposes.

PMID- 17517093
TI  - The growing case for an immunological component to irritable bowel syndrome.

PMID- 17517094
TI  - The efficacy of amino acid-based formulas in relieving the symptoms of cow's milk
      allergy: a systematic review.
AB  - The aim of this systematic review was to evaluate the efficacy of amino acid
      based formulas (AAF) in patients with cow's milk allergy (CMA). Studies were
      identified using electronic databases and bibliography searches. Subjects
      eligible for inclusion were patients of any age with CMA or symptoms suggestive
      of it. Comparisons of interest were AAF vs. extensively hydrolysed formula (eHF),
      AAF vs. soy-based formula (SF) and AAF vs. cow's milk or cow's milk-based
      formula. Outcomes of interest were gastrointestinal (GI), dermatological,
      respiratory and behavioural symptoms as well as growth. A total of 20 studies
      [three head-to-head randomized controlled trials (RCTs), three cross-over
      challenge RCTs, seven clinical trials (CTs) and seven case reports (CRs)] were
      included in the review. In infants with confirmed or suspected CMA, the use of an
      AAF was shown to be safe and efficacious. Findings from RCT comparisons of AAF
      with eHF showed that both formulas are equally efficacious at relieving the
      symptoms of CMA in confirmed or suspected cases. However, infants in specific
      subgroups (e.g. non-IgE mediated food-induced gastro-enterocolitis-proctitis
      syndromes with failure to thrive, severe atopic eczema, or with symptoms during
      exclusive breastfeeding) were more likely overall to benefit from AAF, as
      intolerance to eHF may occur. In such cases, symptoms persisting despite eHF
      feeding usually remit on AAF, and catch-up growth may be seen. Meta-analysis of
      the findings was not possible due to lack of homogenous reporting of outcomes in
      the original trials. This systematic review shows clinical benefit from use of
      AAF in both symptoms and growth in infants and children with CMA who fail to
      tolerate eHF. Further studies are required to determine the relative medical or
      economic value of initial treatment with AAF in infants at high risk of eHF
      intolerance.

PMID- 17517095
TI  - Alterations of food antigen-specific serum immunoglobulins G and E antibodies in
      patients with irritable bowel syndrome and functional dyspepsia.
AB  - BACKGROUND: Post-prandial worsening of symptoms as well as adverse reactions to
      one or more foods are common in the patients with functional gastrointestinal
      diseases, such as irritable bowel syndrome (IBS) and functional dyspepsia (FD).
      However, the role played by true food allergy in the pathogenesis of these
      diseases is still controversial and there are no well-established tests to
      identify food allergy in this condition. OBJECTIVE: To investigate serum food
      antigen-specific IgG, IgE antibody and total IgE antibody titres in controls and
      patients with IBS and FD, and to correlate symptoms with the food antigen
      specific IgG titres in IBS and FD patients. METHODS: Thirty-seven IBS patients,
      28 FD patients and 20 healthy controls participated in this study. Serum IgG and
      IgE antibody titres to 14 common foods including beef, chicken, codfish, corn,
      crab, eggs, mushroom, milk, pork, rice, shrimp, soybean, tomatoes and wheat were
      analysed by ELISA. Serum total IgE titres were also measured. Last,
      symptomatology was assessed in the study. Results IBS patients had significantly
      higher titres of IgG antibody to crab (P=0.000), egg (P=0.000), shrimp (P=0.000),
      soybean (P=0.017) and wheat (P=0.004) than controls. FD patients had
      significantly higher titres of IgG antibody to egg (P=0.000) and soybean
      (P=0.017) than controls. The percentage of individuals with detectable positive
      food antigen-specific IgE antibodies of the three groups did not show any
      significant differences (P=0.971). There were no significant differences between
      IBS patients, FD patients and controls in the serum total IgE antibody titres
      (P=0.978). Lastly, no significant correlation was seen between symptom severity
      and serum food antigen-specific IgG antibody titres both in IBS and FD patients.
      CONCLUSION: Serum IgG antibody titres to some common foods increased in IBS and
      FD patients compared to controls. But there is no significant correlation between
      symptom severity and elevated serum food antigen-specific IgG antibodies in these
      patients.

PMID- 17517096
TI  - Mutational analysis of immunoglobulin E-binding epitopes of beta-casein and beta
      lactoglobulin showed a heterogeneous pattern of critical amino acids between
      individual patients and pooled sera.
AB  - BACKGROUND: For immunotherapeutic approaches, 'critical' amino acids (AAs) within
      allergenic epitopes are replaced with alternate AAs to eliminate IgE antibody
      binding. OBJECTIVE: To determine the critical AAs for IgE binding in beta-casein
      and beta-lactoglobulin (BLG). METHODS: Peptides of 10-14 AAs in length were
      synthesized on a derivatized cellulose membrane with single AA substitutions
      (alanine or glycine) at each position. Membranes were incubated with a pool of
      sera from 15 cow's milk-allergic patients and individual sera from six of the 15
      patients. In cases where no decrease in binding occurred with a single AA
      substitution, peptides with two AA substitutions were generated and labelled.
      RESULTS: Using pooled patient sera, single AA substitutions led to complete
      elimination of binding to six of 11 peptides for beta-casein and to all six
      peptides for BLG. Substituting two AAs led to an elimination of binding to four
      of the remaining five beta-casein epitopes. However, in three of the 11 modified
      beta-casein peptides and five of the six BLG peptides, no decrease in IgE binding
      occurred in at least one individual patient. For these patients, critical AAs
      other than those defined by the patient serum pool were identified, indicating a
      heterogeneous pattern of IgE recognition. CONCLUSION: These results indicate that
      AAs critical for IgE binding are more heterogeneous than initially defined by
      pooled milk-allergic patient sera. For future immunotherapeutic interventions
      with mutated peptides, critical AAs should also be identified with individual
      patient sera to account for heterogeneity of IgE binding between patients.

PMID- 17517097
TI  - Frequency and significance of immediate contact reactions to peanut in peanut
      sensitive children.
AB  - BACKGROUND: Parents of atopic children frequently report, and are alarmed by,
      contact reactions to foods. Some schools restrict foods due to concerns regarding
      possible systemic reactions following contact in allergic children. OBJECTIVE: We
      aimed to determine the frequency with which peanut-sensitive children exhibited
      contact sensitivity to peanut butter and to assess the significance of such
      reactions. METHODS: One gram of peanut butter was applied directly to the skin of
      281 children who were skin prick test (SPT) positive to peanut (immediate skin
      application food test; I-SAFT). The test was considered positive if one or more
      weals were present when the patch was removed after 15 min. A subset of children
      then underwent an open-label oral challenge with graded amounts of peanut
      protein. RESULTS: During 3515 clinic visits, 330 I-SAFT tests for peanut contact
      sensitivity were performed; 136 (41%) were positive. The mean SPT diameter was 10
      mm in the I-SAFT-positive children and 8.5 mm in the I-SAFT-negative children (t
      test, P<0.0001). No child had a systemic reaction following topical application
      of peanut butter. Eighty-four children had 85 oral challenges after blinded,
      placebo-controlled I-SAFT testing. Challenge was positive in 26/32 of those with
      a positive I-SAFT and negative in only 6/32. Challenge was also positive in 26/53
      but negative in 27/53 of those with a negative I-SAFT (sensitivity 50%,
      specificity 82%, chi2, P=0.003). CONCLUSION: A minority of children sensitized to
      peanut (positive SPT) develop localized urticaria from prolonged skin contact
      with peanut butter. No tested subjects, including ones with systemic reactions
      upon oral challenge, developed a systemic reaction to prolonged skin exposure to
      peanut. Therefore, systemic reactions resulting from this mode of contact with
      peanut butter appear highly unlikely.

PMID- 17517098
TI  - Induction of tolerance after establishment of peanut allergy by the food allergy
      herbal formula-2 is associated with up-regulation of interferon-gamma.
AB  - BACKGROUND: Peanut (PN)-anaphylaxis is potentially life threatening. We
      previously reported that a Chinese herbal medicine preparation, food allergy
      herbal formula-2 (FAHF-2), prevented peanut allergy (PNA) in mice when
      administered during sensitization. OBJECTIVE: To investigate whether FAHF-2 also
      can prevent anaphylactic reactions when administered to mice with established PNA
      and, if so, whether protection would persist after cessation of therapy. METHODS:
      C3H/HeJ mice sensitized and boosted over 8 weeks with a standard protocol known
      to establish PN hypersensitivity received seven weeks of FAHF-2 treatment or
      water as a sham treatment. Mice were subsequently challenged with PN at week 14
      (1-day post-therapy) and week 18 (4-week post-therapy) to evaluate the efficacy
      and persistence of FAHF-2 treatment by assessing anaphylactic scores, core body
      temperatures and plasma histamine levels. Serum PN-specific antibody levels and
      cytokine profiles from splenocytes and mesenteric lymph node (MLN) cells were
      also determined. RESULTS: All sham-treated mice challenged at weeks 14 and 18
      showed anaphylactic symptoms. In contrast, FAHF-2-treated mice showed no sign of
      anaphylactic reactions. PN-specific IgE levels in FAHF-2-treated mice also were
      reduced whereas IgG2a levels were increased. Furthermore, MLN cells from FAHF-2
      treated mice produced markedly less IL-4 and IL-5, but more IFN-gamma, and
      contained increased numbers of IFN-gamma-producing CD8+ cells as compared with
      sham-treated mice. CONCLUSION: FAHF-2 treatment established PN tolerance in this
      model, which persisted for at least 4-week post-treatment. This result was
      associated with modulation of intestinal T helper type 1 cell (Th1) and Th2
      cytokine production, and with increased numbers of mesenteric IFN-gamma-producing
      CD8+ cells.

PMID- 17517099
TI  - Maternal allergy influences the proliferation of neonatal T cells expressing
      CCR4, CXCR5 or CD103.
AB  - BACKGROUND: Elevated proliferative response to allergen in cord blood mononuclear
      cells (CBMCs) is related to subsequent allergy development of the neonate and has
      been suggested as a screening marker for high allergy risk. OBJECTIVE: To
      characterize the proliferating cells in CBMCs from a neonatal group influenced by
      maternal allergy compared with a control group without known allergic heredity.
      METHODS: CBMCs were stimulated with bovine beta-lactoglobulin (beta-LG) and
      proliferation was analysed by radioactive thymidine incorporation and expressed
      both as the traditional stimulation index (SI) and SI corrected by eliminating
      non-specific proliferation. After beta-LG combined with endotoxin stimulation,
      cellular expression of IL-4 and IFN-gamma mRNA was determined by quantitative RT
      PCR and adhesion as well as chemokine receptors were analysed by three-colour
      flow cytometry in proliferating T cells (CD3+ Ki-67+). RESULTS: The percentage of
      CCR4+ cells correlated weakly with concurrent IL-4 expression (r(S)=0.5, P<0.05),
      while CXCR3 correlated strongly with IFN-gamma expression (r(S)=0.83, P<0.001).
      In the allergy risk group, the percentage of proliferating T cells expressing
      CCR4 or integrin alphaE (CD103) was significantly reduced compared with the
      control group, while CXCR5 and the corrected SI were relatively increased (CCR4:
      P=0.01; integrin alphaE: P=0.03; CXCR5: P=0.04; SI: P=0.04). CONCLUSION: Our
      results implied delayed maturation of immune functions involved in cellular
      migration, cell-cell interaction and immunoregulatory functions in neonates with
      hereditary allergy risk. The alterations observed in this subject group suggested
      that the corrected SI as well as proliferation of CCR4+, CXCR5+ or CD103+ T cells
      in allergen-stimulated CBMCs might serve as early screening markers for allergy
      risk.

PMID- 17517100
TI  - Association of the single-nucleotide polymorphism and haplotype of the
      interleukin 18 gene with atopic dermatitis in Koreans.
AB  - BACKGROUND: IL-18 is a proinflammatory cytokine that plays an important role for
      T-helper type 1 (Th1) and Th2 cytokine in the presence/absence of IL-12. It has
      been recently shown that human IL-18 plays a role in atopic dermatitis (AD) by
      enhancing IL-4 and IL-13 production and by stimulating the synthesis of IgE.
      OBJECTIVE: We wanted to evaluate the associations of single-nucleotide
      polymorphism (SNP) and the haplotype in the IL-18 gene, hence we performed
      genotyping for the SNPs in the IL-18 gene in AD patients and normal controls.
      METHOD: We genotyped three SNPs from the IL-18 gene for the 1120 case-control
      samples (646 AD patients and 474 normal controls). We measured the serum IL-18,
      IL-4 and IL-13 concentrations in 74 individuals (25 ADe, 25 ADi and 24 controls)
      by performing ELISA. RESULT: The rs795467 SNP and haplotype T-T-C were
      significantly associated with AD, and especially between the ADe and normal
      control groups (P=0.03 and 0.01). The serum IL-18 concentration was higher in the
      AD group than in the normal controls without any correlation with the rs795467
      polymorphism. We did not find any correlations between the serum IL-18 levels and
      the SCORing atopic dermatitis index, the blood eosinophil counts and the ECP, and
      there was no correlation between the serum IL-18 levels and the serum IL-4 and IL
      13 levels. CONCLUSION: We found that the one SNP and the haplotype T-T-C were
      strongly associated with the allergic type of AD, but not with the non-allergic
      intrinsic type. These data support the hypothesis that IL-18 up-regulates IgE
      production, yet more experiments will be needed to prove the in vivo involvement
      of Th2 cytokine.

PMID- 17517101
TI  - Matrix metalloproteases in vernal keratoconjunctivitis, nasal polyps and allergic
      asthma.
AB  - BACKGROUND: Allergic conditions in different organs share many similarities in
      their inflammatory response. Vernal keratoconjunctivitis (VKC), asthma and nasal
      polyps exhibit several similar, but site-specific mucosal structural changes. The
      aim of the study was to investigate whether matrix metalloproteases contribute to
      different tissue remodelling aspects in different organs. METHODS: Mucosal
      biopsies were obtained from conjunctiva of healthy donors, tarsal conjunctiva of
      vernal patients, bronchi of non-asthmatic subjects, bronchi of mild stable
      asthmatic patients, nasal mucosa of non-allergic donors and nasal polyps of
      allergic patients. Distribution of metalloprotease-1, -3, -9, -13, tissue
      inhibitor of metalloproteases-1, collagens I and III and the presence of
      eosinophils and CD4+ cells were evaluated by immunohistochemistry. RESULTS:
      Collagens were highly diffuse in the giant papillae of VKC and in nasal polyps,
      and yet less increased in the subepithelium of asthmatic patients. Immunostaining
      for metalloprotease-1, -3, -9 and -13 was significantly higher in VKC compared
      with normal conjunctiva. Metalloprotease-9 staining was higher in the stroma of
      polyps vs. normal nasal mucosa, and only metalloprotease-13 was significantly
      more expressed in asthmatic vs. non-asthmatic subjects. Metalloprotease-9
      immunostaining was more intense in vernal compared with other tissues. In all
      pathological tissues, metalloprotease-9-positive staining was in association with
      eosinophils and CD4+ cells. CONCLUSIONS: Expression of metalloproteases may play
      an important role in inducing the structural changes seen in VKC, nasal polyps
      and asthma. Tissue remodelling and gelatinase immunoexpression was more dramatic
      in giant papillae of vernal patients compared with other tissue sites of chronic
      allergic inflammation.

PMID- 17517102
TI  - Human bronchial epithelial cells express an active and inducible biosynthetic
      pathway for leukotrienes B4 and C4.
AB  - BACKGROUND: Human bronchial epithelial cells synthesize cyclooxygenase and 15
      lipoxygenase products, but the 5-lipoxygenase (5-LO) pathway that generates the
      leukotriene (LT) family of bronchoconstrictor and pro-inflammatory mediators is
      thought to be restricted to leucocytes. OBJECTIVE: We hypothesized that human
      bronchial epithelial cells (HBECs) express a complete and active 5-LO pathway for
      the synthesis of LTB4 and LTC4, either constitutively or after stimulation.
      METHODS: Flow cytometry, RT-PCR, Western blotting, enzyme immunoassays and
      reverse-phase high-performance liquid chromatography were used to investigate
      constitutive and stimulated expression of 5-LO pathway enzymes and the synthesis
      of LTs B4 and C4 in primary HBECs and in the 16-HBE 14o- cell line. RESULTS:
      Constitutive mRNA and protein expression for 5-LO, 5-LO-activating protein
      (FLAP), LTA4 hydrolase and LTC4 synthase were demonstrated in primary HBECs and
      in the 16-HBE 14o- cell line. In 16-HBE 14o- cells, treatment with calcium
      ionophore A23187, bradykinin or LPS up-regulated the expression of these enzymes.
      The up-regulation of 5-LO was blocked by the anti-inflammatory glucocorticoid
      dexamethasone. Human bronchial epithelial cells were shown to generate bioactive
      LTs, with primary HBECs generating 11-fold more LTC4 and five-fold more LTB4 than
      16-HBE 14o- cells. LT production was enhanced by ionophore treatment and blocked
      by the FLAP inhibitor MK-886. CONCLUSIONS: Expression of an active and inducible
      5-LO pathway in HBEC suggests that damaged or inflamed bronchial epithelium may
      synthesize LTs that contribute directly to bronchoconstriction and leucocytosis
      in airway inflammation.

PMID- 17517103
TI  - Roles of P2X receptors and Ca2+ sensitization in extracellular adenosine
      triphosphate-induced hyperresponsiveness in airway smooth muscle.
AB  - BACKGROUND: The release of adenosine triphosphate (ATP) from the airway
      epithelial cells during the inflammatory process is considered to play an
      important role in the pathophysiology of asthma and chronic obstructive pulmonary
      disease. OBJECTIVE: This study was designed to determine whether extracellular
      ATP is involved in the bronchial hyperresponsiveness as an interaction between
      epithelium and smooth muscle in the airways. METHODS: We examined the contractile
      response to methacholine (MCh) before and after exposure to low concentrations (<
      or = 10 microm) of ATP in isolated, epithelium-denuded guinea-pig tracheal smooth
      muscle by measuring isometric tension. Intracellular Ca2+ concentrations
      ([Ca2+]i) were assessed by fluorescent intensities of fura-2. RESULTS: MCh
      induced contractile force was increased with no change in [Ca2+]i after exposure
      to 10 microm ATP for 15 min. The ability of ATP to enhance the MCh-induced
      contraction was markedly attenuated by suramin, a non-selective P2 receptor
      inhibitor. Pre-incubation with ATPgammaS, a non-hydrolysable analogue of ATP and
      alpha,beta-meATP, a P2X agonist, also enhanced the MCh-induced contraction. In
      contrast, uracil triphosphate, a P2Y agonist, did not affect the MCh-induced
      contraction. Y-27632, a Rho-kinase inhibitor, suppressed the ability of ATP to
      enhance the MCh-induced contraction. Moreover, PP1 and PP2, Src tyrosin kinase
      inhibitors, suppressed the enhancement of MCh-induced contraction by ATP.
      CONCLUSION: Pre-treatment with ATP induces hyperresponsiveness to MCh mediated by
      Ca2+ sensitization via the P2X receptor in airway smooth muscle. The present
      findings suggest the possible involvement of both the Rho-kinase and Src pathways
      in the intracellular mechanism of this phenomenon.

PMID- 17517104
TI  - Immunoreactivity profile of peripheral blood mononuclear cells from patients with
      ragweed-induced allergic rhinitis.
AB  - BACKGROUND: Seasonal rhinitis is manifested by a series of nasal symptoms in
      response to exposure to seasonal allergens including ragweed pollen.
      Understanding its immunological mechanisms may help to better manage the disease.
      OBJECTIVE: We sought to determine comprehensively ragweed-induced cytokine and
      chemokine production by peripheral blood mononuclear cells from normal
      individuals and patients with seasonal rhinitis sensitized to ragweed pollen, and
      to assess its regulation by exogenous IL-10. METHODS: Cells were cultured in the
      presence or absence of a purified ragweed pollen extract with or without
      exogenous IL-10. Cytokines and chemokines were measured in the supernatant. Gene
      expression was evaluated using real-time quantitative reverse transcription PCR.
      RESULTS: Ragweed stimulation significantly increased the production of the Th2
      associated cytokines IL-5, IL-9 and IL-13, the chemokines CCL17 and CCL22 and the
      regulatory cytokine IL-10 in allergic patients, whereas transforming growth
      factor-beta (TGF-beta) production was increased only in normal individuals. No
      difference was detected between groups in the production of the Th1 cytokine IFN
      gamma or the Th1-affiliated chemokines CXCL10 and CXCL11. Exogenous IL-10
      significantly suppressed spontaneous and induced production of both Th1- and Th2
      associated cytokines and chemokines. CONCLUSION: Our work demonstrated that
      locally manifested allergic rhinitis is underlined by a systemic Th2 immune
      response specific to allergens. The molecular pathogenesis of allergic rhinitis
      may be linked to a compromised allergen-specific immune regulation, e.g., reduced
      spontaneous and allergen-induced TGF-beta production in patients compared with
      healthy controls. Our data also show that IL-10 inhibits both the effector and
      directional mechanisms of allergen-specific immune response, further supporting
      its potential therapeutic benefit in preventing and treating allergic diseases.

PMID- 17517105
TI  - Effect of tecastemizole on pulmonary and cutaneous allergic inflammatory
      responses.
AB  - BACKGROUND: Tecastemizole, a major metabolite of astemizole, is a potent and
      selective H1 receptor antagonist. Evidence suggests that this and certain other
      H1 receptor antagonists may possess anti-inflammatory effects that are, in some
      cases, independent of H1 receptor antagonism. Objective The aim of this study was
      to investigate the anti-inflammatory effects of tectastemizole in models of
      allergic inflammation. METHODS: Effects of tecastemizole were assessed in a
      murine model of allergic lung inflammation, in passive cutaneous anaphylaxis
      (PCA) responses in guinea-pig skin and in in vitro assays measuring endothelial
      adhesion molecule expression and leucocyte-endothelial adhesion. RESULTS:
      Tecastemizole inhibited antigen-induced eosinophil recruitment to the lungs of
      allergic mice in a dose-dependent manner. Furthermore, combination of a sub
      effective dose of tecastemizole, combined with a sub-effective dose of
      dexamethasone inhibited eosinophil accumulation in this model. Plasma
      extravasation in PCA reactions was inhibited by tecastemizole, although by a
      mechanism that would appear to be H1 receptor-dependent. Cytokine-induced
      endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule
      1 expression, as well as mononuclear cell adhesion to human umbilical vein
      endothelial cells was inhibited by tecastemazole in a manner independent of H1
      receptor antagonism. CONCLUSION: These data suggest that tecastemizole may have
      H1 receptor-independent effects in inhibiting late-phase inflammatory responses,
      while acute responses appear to be inhibited in a H1 receptor-dependent manner.
      Furthermore, our data suggest an important potential steroid-sparing role for
      such drugs in the treatment of allergic inflammatory conditions.

PMID- 17517106
TI  - Genetically glycosylated ovomucoid third domain can modulate Immunoglobulin E
      antibody production and cytokine response in BALB/c mice.
AB  - BACKGROUND: Food allergies are on the rise and it is estimated that in North
      America, 8% of the children and 4% of the adults have food allergies. Food
      allergies tend to occur more often in children than in adults due to their
      immature digestive and immune systems. Hen's egg is among the most common cause
      of food-induced allergic reactions in North America. OBJECTIVE: The present study
      was undertaken to investigate the role of N-glycans of the third domain of
      ovomucoid in IgE binding and modulation of allergen-specific immune response in
      BALB/c mice. METHODS: The cDNA encoding the third domain of ovomucoid was
      inserted into the yeast genome and expressed in Pichia pastoris X-33 cells, under
      the control of the glyceraldehyde-3-phosphate (GAP) dehydrogenase promoter for
      constitutive expression to obtain a post-translationally modified and
      functionally active ovomucoid third domain. Upon expression, the protein was
      secreted into the extracellular medium and was purified by size exclusion
      chromatography. The recombinant protein was produced at 10 mg/L of the culture
      supernatant. BALB/c mice were sensitized with the recombinant and native forms of
      glycosylated ovomucoid third domain antigen. The allergic response of the native
      and the recombinant glycosylated forms of ovomucoid third domain antigens were
      compared using antibody and cytokine measurements. RESULTS: ELISA tests indicated
      a significant decrease in specific IgE antibodies to the recombinant N-linked
      glycosylated form (P-Gly), when compared with the native glycosylated form
      (DIII+) using mice sera. Immunization with P-Gly induced the production of IFN
      gamma [T-helper type 1 (Th1) response] and lowered the production of IL-4 (Th2
      response), and a skewed balance towards the Th1 cytokine demonstrated that P-Gly
      has a modulating ability on Th1/Th2 balance to down-regulate Th2 response.
      Furthermore, N-linked glycan (N28) in the third domain of ovomucoid was shown to
      be associated with suppression of the allergic response. CONCLUSION: Therefore,
      we can conclude that P-Gly facilitates and contributes to the discovery of new
      molecular target for the development of a safe and specific therapeutic vaccine
      for the treatment of egg allergy, and oligosaccharides do seem to play a major
      role in the suppression of IgE-binding activity.

PMID- 17517107
TI  - Ses i 6, the sesame 11S globulin, can activate basophils and shows cross
      reactivity with walnut in vitro.
AB  - BACKGROUND: Sesame allergy is increasingly being reported, and multi
      sensitization to peanut and tree nuts has been described. The clinical relevance
      and cross-reactivity of many sesame proteins, such as Ses i 6, are unknown.
      OBJECTIVE: The aims of this study were to perform a preliminary examination of
      the cross-reactivity of Ses i 6 in vitro, examine the ability of Ses i 6 to
      activate basophils in a modified basophil activation test (mBAT), and assess
      whether such an assay may help to distinguish between potentially relevant and
      irrelevant IgE reactivity towards 11S globulin proteins. METHODS: Inhibition
      immunoblotting and chicken anti-rJug r 4 antibodies were used to determine the
      cross-reactivity of rSes i 6. Basophils from atopic donors were stripped of
      resident IgE before passive sensitization with food-allergic sera and challenged
      with protein extracts or recombinant protein. Basophil activation was measured
      using two activation markers, CD203c and CD63, via flow cytometry. RESULTS: IgE
      immunoblotting showed cross-reactivity between rJug r 4 and rSes i 6 using sera
      from two human donors and chicken IgY. Additionally, rSes i 6 activated basophils
      passively sensitized with sesame-allergic sera. Cross-reactive serum from a
      sesame-allergic but walnut-tolerant donor was not able to activate basophils when
      challenged by walnut extract despite IgE reactivity to walnut determined by
      immunoblotting. CONCLUSIONS: The sesame 11S globulin shows partial immunological
      cross-reactivity with walnut, and although it is classified as a minor allergen,
      activated basophils sensitized with serum from seven out of eleven sesame
      allergic donors. Additionally, the mBAT may help distinguish between clinically
      relevant and irrelevant in vitro IgE cross-reactivity of seed storage proteins in
      nuts and seeds and thus warrants use in further studies.

PMID- 17517108
TI  - The major horse allergen Equ c 1 contains one immunodominant region of T cell
      epitopes.
AB  - BACKGROUND: Despite the fact that most significant mammalian respiratory
      allergens are lipocalin proteins, information on the human T cell reactivity to
      these allergenic proteins is largely missing. OBJECTIVE: Knowing the T cell
      epitopes in allergens is a prerequisite for developing novel preparations for
      allergen immunotherapy. METHODS: Specific T cell lines were generated with
      recombinant Equ c 1 from the peripheral blood mononuclear cells (PBMCs) of 10
      horse-allergic subjects. For determining T cell epitopes, the lines were
      stimulated with 16mer synthetic Equ c 1 peptides overlapping by 14 amino acids.
      The binding capacity of Equ c 1 peptides to human leucocyte antigen class II
      molecules was determined by the competitive ELISA. RESULTS: The major horse
      allergen Equ c 1 resembles two other lipocalin allergens, the major cow allergen
      Bos d 2 and the major dog allergen Can f 1, in that it is weakly stimulatory for
      the PBMCs of sensitized subjects. Moreover, the T cell epitopes of Equ c 1 are
      clustered in a few regions along the molecule, as is the case with Bos d 2 and
      Can f 1. Similar to Bos d 2, Equ c 1 contains one immunodominant epitope region
      at the carboxy-terminal end of the molecule. The T cell lines of eight horse
      allergic subjects out of 10 showed strong reactivity to one or both of the two
      overlapping peptides, p143-158 and p145-160, in this region. The region probably
      contains two overlapping epitopes. CONCLUSION: The 18mer peptide p143-160 from
      the immunodominant region of Equ c 1 is a potential candidate for the peptide
      based immunotherapy of horse-sensitized subjects.

PMID- 17517109
TI  - A prospective study of allergy development in 158 children and 128 adults with
      new extensive exposure to furred animals.
AB  - BACKGROUND: There is still controversy over whether exposure to furred animals
      increases or decreases the risk of developing sensitization and allergic symptoms
      to such animals, and there is a need for further knowledge on this subject.
      OBJECTIVE: The aim of this study was to follow allergy development in relation to
      new extensive exposure to furred animals in adults and children. METHODS: A total
      of 286 individuals, 128 parents and 158 children, were recruited from 68 families
      who intended to buy a dog or a cat, or where one child of the family intended to
      start riding a horse. Subjects were examined before the new allergen exposure and
      once a year thereafter for 5 years, in all at six occasions, and they also
      completed questionnaires covering allergy symptoms. Serum IgE antibodies to cat,
      dog and horse were determined each year, and fur allergens from beds and living
      rooms were analysed. RESULTS: Two-hundred and fifty-six study subjects remained
      for evaluation, 37 of whom showed signs of allergic sensitization at the start of
      the study. Four children (11%) in this pre-sensitized group developed IgE
      antibodies to their new animal and six (16%) to another animal. Among the 219
      participants who were not sensitized when entering the study, one male adult
      (0.4%) developed a sensitization to his new animal, and nobody developed
      sensitization to other animals. Pre-sensitized individuals had significantly more
      allergic symptoms at the study start, but the symptom scores did not change over
      time. CONCLUSIONS: When the first year of a human's life has passed, we have no
      strong evidence to recommend avoidance of a domestic animal in order to prevent
      new allergy development, even if there are known allergies in the family or if
      the individual is sensitized and has allergic symptoms to another allergen. Five
      years exposure to new fur allergens does not seem to influence sensitization to
      these animals in either sensitized or non-sensitized children and adults.

PMID- 17517110
TI  - Allergic rhinitis and asthma comorbidity: ARIA classification of rhinitis does
      not correlate with the prevalence of asthma.
AB  - BACKGROUND: Allergic rhinitis and asthma comorbidity is supported by both the
      similar underlying pathogenesis and immunologic mechanisms. The aim of this study
      was to verify whether the characteristics of rhinitis classified according to the
      new Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines correlate with
      the prevalence of asthma. METHODS: From 1 March to 30 June 2002, a multi-centre
      cross-sectional study was conducted by 154 allergists chosen from throughout
      Italy. Duration, severity of rhinitis (according to the ARIA classification) and
      the type of allergic sensitizations were compared with the prevalence of asthma.
      RESULTS: One thousand three hundred and twenty-one consecutive rhinitis-allergic
      patients aged 18 years or older were enrolled for the study. The majority of
      patients, 1060 (80.24%), were on medication at the time of their specialist
      visit. Mild intermittent rhinitis was diagnosed in 7.7% of patients,
      moderate/severe intermittent in 17.1%, mild persistent in 11.6%, and
      moderate/severe persistent in 63.6%. The prevalence of asthma was 48% in patients
      with mild intermittent rhinitis, 49.6% in moderate-severe intermittent rhinitis,
      36.6% in mild persistent rhinitis and 47.5% in moderate severe persistent
      patients. No correlation between the ARIA categories of rhinitis and the
      prevalence of asthma was found. A multivariate analysis, after adjustment for
      age, sex, type of sensitization, level of severity and duration of rhinitis
      classified according to the ARIA guidelines, demonstrated that age, over 41 years
      [risk ratio (RR) 1.260, 95% confidence interval (CI) 1.072-1.482] and especially
      over 51 years (RR 1.460, 95% CI 1.237-1.723), sensitization to indoor allergens
      (mite and cat), (RR 1.203, 95% CI 1.060-1.366), and polysensitization (RR 1.178,
      95% CI 1.004-1.383) are significant risk factors for asthma. CONCLUSION: In
      allergic rhinitis (AR) patients referred to a specialist, the features of AR as
      defined by the ARIA classification are not able to predict the presence of
      asthma, therefore all such patients should be assessed for asthma.

PMID- 17517112
TI  - Using population segmentation to provide better health care for all: the "Bridges
      to Health" model.
AB  - The model discussed in this article divides the population into eight groups:
      people in good health, in maternal/infant situations, with an acute illness, with
      stable chronic conditions, with a serious but stable disability, with failing
      health near death, with advanced organ system failure, and with long-term
      frailty. Each group has its own definitions of optimal health and its own
      priorities among services. Interpreting these population-focused priorities in
      the context of the Institute of Medicine's six goals for quality yields a
      framework that could shape planning for resources, care arrangements, and service
      delivery, thus ensuring that each person's health needs can be met effectively
      and efficiently. Since this framework would guide each population segment across
      the institute's "Quality Chasm," it is called the "Bridges to Health" model.

PMID- 17517114
TI  - Counting backward to health care's future: using time-to-death modeling to
      identify changes in end-of-life morbidity and the impact of aging on health care
      expenditures.
AB  - In most developed countries, as the largest population cohorts approach the age
      of sixty-five, the impact of population aging on health care expenditures has
      become a topic of growing interest. This articles examines trends in elderly
      disability and end-of-life morbidity, estimations of the cost of dying, and
      models of expenditures as a function of both age and time-to-death and finds
      broad improvement in mortality and morbidity among the elderly in the developed
      world. Reduced mortality and low growth in the costs associated with dying could
      reduce forecasted expenditures, but high growth in expenditures for those not
      close to death and for nonhospital services could create new economic pressures
      on health care systems.

PMID- 17517115
TI  - Damages caps in medical malpractice cases.
AB  - This article reviews the empirical literature on the effects of damages caps and
      concludes that the better-designed studies show that damages caps reduce
      liability insurance premiums. The effects of damages caps on defensive medicine,
      physicians' location decisions, and the cost of health care to consumers are less
      clear. The only study of whether consumers benefit from lower health insurance
      premiums as a result of damages caps found no impact. Some state courts have
      based decisions declaring damages caps legislation unconstitutional on the lack
      of evidence of their effectiveness, thereby ignoring the findings of conflicting
      research studies or discounting their relevance. Although courts should be
      cautious in rejecting empirical evidence that caps are effective, legislators
      should consider whether they benefit consumers enough to justify limiting tort
      recoveries for those most seriously injured by malpractice.

PMID- 17517116
TI  - Commentary: binding early offers versus caps for medical malpractice claims?
AB  - Like damages caps, early offer reform promises reduction in the costs of medical
      liability cases. In contrast to damages caps, early offer reform offers
      advantages to both claimant and defendant. Under early offer, the defendant would
      have the option to offer an injured patient periodic payments for the patient's
      net economic losses as they accrue, but not payments for noneconomic losses (pain
      and suffering). If an early offer were made and accepted, that would settle the
      claim. This commentary(1) explains how an early offer reform might work and
      summarizes data from a recent closed claim study of medical malpractice cases in
      Texas and Florida. The data show widespread opportunities for successful early
      offers and provide evidence that substantial per case savings would result.

PMID- 17517117
TI  - Commentary: malpractice reform in policy perspective.
AB  - Enacted caps on malpractice awards and proposed early offer reform address the
      sometimes excessive verdicts of conventional liability and its very high overhead
      costs. However, such reforms greatly benefit medical defendants while doing too
      little for claimants or patients in general. Caps and early offer only affect
      current claims; far broader reforms are therefore needed to improve the woeful
      performance of liability as a general promoter of patient safety and injury
      compensation. Broad reforms, however desirable, seldom surmount high political
      and practical hurdles. A good, more evenhanded start would seek to make claims
      resolution faster, more accurate, more predictable, and less expensive, while
      separately promoting medical quality and safety as well as greater transparency
      for law, medicine, and insurance.

PMID- 17517118
TI  - Hospitals' strategies for orchestrating selection of physician preference items.
AB  - This article analyzes hospitals' strategies to shape physicians' behavior and
      counter suppliers' power in purchasing physician preference items. Two models of
      standardization are limitations on the range of manufacturers or products (the
      "formulary" model) and price ceilings for particular item categories (the
      "payment-cap" model), both requiring processes to define product equivalencies
      often with inadequate product comparison data. The formulary model is more
      difficult to implement because of physicians' resistance to top-down dictates.
      The payment-cap model is more feasible because it preserves physicians' choice
      while also restraining manufacturers' power. Hospitals may influence physicians'
      involvement through a process of orchestration that includes committing to
      improve clinical facilities, scheduling, and training and fostering a culture of
      mutual trust and respect.

PMID- 17517120
TI  - STATc is a key regulator of the transcriptional response to hyperosmotic shock.
AB  - BACKGROUND: Dictyostelium discoideum is frequently subjected to environmental
      changes in its natural habitat, the forest soil. In order to survive, the
      organism had to develop effective mechanisms to sense and respond to such
      changes. When cells are faced with a hypertonic environment a complex response is
      triggered. It starts with signal sensing and transduction and leads to changes in
      cell shape, the cytoskeleton, transport processes, metabolism and gene
      expression. Certain aspects of the Dictyostelium osmotic stress response have
      been elucidated, however, no comprehensive picture was available up to now.
      RESULTS: To better understand the D. discoideum response to hyperosmotic
      conditions, we performed gene expression profiling using DNA microarrays. The
      transcriptional profile of cells treated with 200 mM sorbitol during a 2-hour
      time course revealed a time-dependent induction or repression of 809 genes, more
      than 15% of the genes on the array, which peaked 45 to 60 minutes after the
      hyperosmotic shock. The differentially regulated genes were applied to cluster
      analysis and functional annotation using gene GO terms. Two main responses appear
      to be the down-regulation of the metabolic machinery and the up-regulation of the
      stress response system, including STATc. Further analysis of STATc revealed that
      it is a key regulator of the transcriptional response to hyperosmotic shock.
      Approximately 20% of the differentially regulated genes were dependent on the
      presence of STATc. CONCLUSION: At least two signalling pathways are activated in
      Dictyostelium cells subjected to hypertonicity. STATc is responsible for the
      transcriptional changes of one of them.

PMID- 17517119
TI  - Development of a policy-relevant child maltreatment research strategy.
AB  - Child maltreatment is associated with a huge burden of suffering, yet there are
      serious gaps in knowledge about its epidemiology and approaches to intervention.
      This article describes the development of a proposed national research framework
      in child maltreatment, as requested by the Department of Justice, Canada, based
      on (1) a review of the literature, (2) consultation with experts, and (3)
      application of evaluation criteria for considering research priorities. The
      article identifies gaps in knowledge about child maltreatment in Canada and
      proposes a research agenda to make evidence-based policy decisions more likely.
      Although this work was driven by gaps in Canada's knowledge about child
      maltreatment, the international scope of the review and consultation process
      could make the findings useful to broader research and policy audiences.

PMID- 17517121
TI  - Toxin production in a rare and genetically remote cluster of strains of the
      Bacillus cereus group.
AB  - BACKGROUND: Three enterotoxins are implicated in diarrhoeal food poisoning due to
      Bacillus cereus: Haemolysin BL (Hbl), Non-haemolytic enterotoxin (Nhe), and
      Cytotoxin K (CytK). Toxin gene profiling and assays for detection of toxin
      producing stains have been used in attempts to evaluate the enterotoxic potential
      of B. cereus group strains. B. cereus strain NVH 391/98, isolated from a case of
      fatal enteritis, was genetically remote from other B. cereus group strains. This
      strain lacked the genes encoding Hbl and Nhe, but contains CytK-1. The high
      virulence of this strain is thought to be due to the greater cytotoxic activity
      of CytK-1 compared to CytK-2, and to a high level of cytK expression. To date,
      only three strains containing cytK-1 have been identified; B. cereus strains NVH
      391/98, NVH 883/00, and INRA AF2. RESULTS: A novel gene variant encoding Nhe was
      identified in these three strains, which had an average of 80% identity in
      protein sequence with previously identified Nhe toxins. While culture
      supernatants containing CytK and Nhe from NVH 391/98 and INRA AF2 were highly
      cytotoxic, NVH 883/00 expressed little or no CytK and Nhe and was non-cytotoxic.
      Comparative sequence and expression studies indicated that neither the PlcR/PapR
      quorum sensing system, nor theYvrGH and YvfTU two-component systems, were
      responsible for the observed difference in toxin production. Additionally,
      phylogenetic analysis of 13 genes showed that NVH 391/98, NVH 883/00, and INRA
      AF2 comprise a novel cluster of strains genetically distant from other B. cereus
      group strains. CONCLUSION: Due to its divergent sequence, the novel nhe operon
      had previously not been detected in NVH 391/98 using PCR and several monoclonal
      antibodies. Thus, toxigenic profiling based on the original nhe sequence will
      fail to detect the toxin in this group of strains. The observation that strain
      NVH 883/00 carries cytK-1 but is non-cytotoxic indicates that the detection of
      this gene variant is not a sufficient criterion for identification of highly
      cytotoxic strains. The presence of the novel nhe operon and the cytK-1 gene
      variant in this cluster of strains reflect their phylogenetically remote
      relationship towards other B. cereus group strains.

PMID- 17517122
TI  - The standardized surgical approach improves outcome of gallbladder cancer.
AB  - BACKGROUND: The objective of this study was to examine the extent of surgical
      procedures, pathological findings, complications and outcome of patients treated
      in the last 12 years for gallbladder cancer. METHODS: The impact of a
      standardized more aggressive approach compared with historical controls of our
      center with an individual approach was examined. Of 53 patients, 21 underwent
      resection for cure and 32 for palliation. RESULTS: Overall hospital mortality was
      9% and procedure related mortality was 4%. The standardized approach in UICC
      stage IIa, IIb and III led to a significantly improved outcome compared to
      patients with an individual approach (Median survival: 14 vs. 7 months, mean+/
      SEM: 26+/-7 vs. 17+/-5 months, p = 0.014). The main differences between the
      standardized and the individual approach were anatomical vs. atypical liver
      resection, performance of systematic lymph dissection of the hepaticoduodenal
      ligament and the resection of the common bile duct. CONCLUSION: Anatomical liver
      resection, proof for bile duct infiltration and, in case of tumor invasion,
      radical resection and lymph dissection of the hepaticoduodenal ligament are
      essential to improve outcome of locally advanced gallbladder cancer.

PMID- 17517123
TI  - Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate
      toll-like receptors.
AB  - BACKGROUND: Toll-like receptors (TLRs) play a central role in innate immunity.
      TLRs are membrane glycoproteins and contain leucine rich repeat (LRR) motif in
      the ectodomain. TLRs recognize and respond to molecules such as
      lipopolysaccharide, peptidoglycan, flagellin, and RNA from bacteria or viruses.
      The LRR domains in TLRs have been inferred to be responsible for molecular
      recognition. All LRRs include the highly conserved segment, LxxLxLxxNxL, in which
      "L" is Leu, Ile, Val, or Phe and "N" is Asn, Thr, Ser, or Cys and "x" is any
      amino acid. There are seven classes of LRRs including "typical" ("T") and
      "bacterial" ("S"). All known domain structures adopt an arc or horseshoe shape.
      Vertebrate TLRs form six major families. The repeat numbers of LRRs and their
      "phasing" in TLRs differ with isoforms and species; they are aligned differently
      in various databases. We identified and aligned LRRs in TLRs by a new method
      described here. RESULTS: The new method utilizes known LRR structures to
      recognize and align new LRR motifs in TLRs and incorporates multiple sequence
      alignments and secondary structure predictions. TLRs from thirty-four vertebrate
      were analyzed. The repeat numbers of the LRRs ranges from 16 to 28. The LRRs
      found in TLRs frequently consists of LxxLxLxxNxLxxLxxxxF/LxxLxx ("T") and
      sometimes short motifs including LxxLxLxxNxLxxLPx(x)LPxx ("S"). The TLR7 family
      (TLR7, TLR8, and TLR9) contain 27 LRRs. The LRRs at the N-terminal part have a
      super-motif of STT with about 80 residues. The super-repeat is represented by
      STTSTTSTT or _TTSTTSTT. The LRRs in TLRs form one or two horseshoe domains and
      are mostly flanked by two cysteine clusters including two or four cysteine
      residue. CONCLUSION: Each of the six major TLR families is characterized by their
      constituent LRR motifs, their repeat numbers, and their patterns of cysteine
      clusters. The central parts of the TLR1 and TLR7 families and of TLR4 have more
      irregular or longer LRR motifs. These central parts are inferred to play a key
      role in the structure and/or function of their TLRs. Furthermore, the super
      repeat in the TLR7 family suggests strongly that "bacterial" and "typical" LRRs
      evolved from a common precursor.

PMID- 17517124
TI  - Mutation accumulation and fitness effects in hybridogenetic populations: a
      comparison to sexual and asexual systems.
AB  - BACKGROUND: Female only unisexual vertebrates that reproduce by hybridogenesis
      show an unusual genetic composition. They are of hybrid origin but show no
      recombination between the genomes of their parental species. Instead, the
      paternal genome is discarded from the germline prior to meiosis, and gametes
      (eggs only) contain solely unrecombined maternal genomes. Hence hybridogens only
      transmit maternally inherited mutations. Hybridity is restored each generation by
      backcrossing with males of the sexual parental species whose genome was
      eliminated. In contrast, recombining sexual species propagate an intermixed pool
      of mutations derived from the maternal and paternal parts of the genome. If
      mutation rates are lower in female gametes than males, it raises the possibility
      for lower mutation accumulation in a hybridogenetic population, and consequently,
      higher population fitness than its sexual counterpart. RESULTS: We show through
      Monte-Carlo simulations that at higher male to female mutation ratios, and
      sufficiently large population sizes, hybridogenetic populations can carry a lower
      mutation load than sexual species. This effect is more pronounced with
      synergistic forms of epistasis. Mutations accumulate faster on the sexual part of
      the genome, and with the purifying effects of epistasis, it makes it more
      difficult for mutations to be transmitted on the clonal part of the genome. In
      smaller populations, the same mechanism reduces the speed of Muller's Ratchet and
      the number of fixed mutations compared to similar asexual species. CONCLUSION:
      Since mutation accumulation can be less pronounced in hybridogenetic populations,
      the question arises why hybridogenetic organisms are so scarce compared to sexual
      species. In considering this, it is likely that comparison of population
      fitnesses is not sufficient. Despite competition with the sexual parental
      species, hybrid populations are dependent on the maintenance of--and contact with
      -their sexual counterpart. Other problems may involve too little genetic
      diversity to respond to changing environments and problems in becoming
      hybridogenetic (e.g. disruption of meiosis and subsequent infertility or
      sterility). Yet, lower mutation accumulation in hybridogenetic populations opens
      the possibility that hybridogenetic species can develop into new sexual species
      once recombination is re-established and reproductive isolation from sexual
      ancestors has occurred.

PMID- 17517125
TI  - Genetic and phylogenetic evolution of HIV-1 in a low subtype heterogeneity
      epidemic: the Italian example.
AB  - The Human Immunodeficiency Virus type 1 (HIV-1) is classified into genetic
      groups, subtypes and sub-subtypes which show a specific geographic distribution
      pattern. The HIV-1 epidemic in Italy, as in most of the Western Countries, has
      traditionally affected the Intra-venous drug user (IDU) and Homosexual (Homo)
      risk groups and has been sustained by the genetic B subtype. In the last years,
      however, the HIV-1 transmission rate among heterosexuals has dramatically
      increased, becoming the prevalent transmission route. In fact, while the
      traditional risk groups have high levels of knowledge and avoid high-risk
      practices, the heterosexuals do not sufficiently perceive the risk of HIV-1
      infection. This misperception, linked to the growing number of immigrants from
      non-Western Countries, where non-B clades and circulating recombinant forms
      (CRFs) are prevalent, is progressively introducing HIV-1 variants of non-B
      subtype in the Italian epidemic. This is in agreement with reports from other
      Western European Countries. In this context, the Italian HIV-1 epidemic is still
      characterized by low subtype heterogeneity and represents a paradigmatic example
      of the European situation. The continuous molecular evolution of the B subtype
      HIV-1 isolates, characteristic of a long-lasting epidemic, together with the
      introduction of new subtypes as well as recombinant forms may have significant
      implications for diagnostic, treatment, and vaccine development. The study and
      monitoring of the genetic evolution of the HIV-1 represent, therefore, an
      essential strategy for controlling the local as well as global HIV-1 epidemic and
      for developing efficient preventive and therapeutic strategies.

PMID- 17517126
TI  - The predictive value of post-traumatic stress disorder symptoms for quality of
      life: a longitudinal study of physically injured victims of non-domestic
      violence.
AB  - BACKGROUND: Little is known about longitudinal associations between post
      traumatic stress disorder (PTSD) and quality of life (QoL) after exposure to
      violence. The aims of the current study were to examine quality of life (QoL) and
      the predictive value of post-traumatic stress disorder (PTSD) for QoL in victims
      of non-domestic violence over a period of 12 months. METHODS: A single-group (n =
      70) longitudinal design with three repeated measures over a period of 12 months
      were used. Posttraumatic psychological symptoms were assessed by using the Impact
      of Event Scale, a 15-item self-rating questionnaire comprising two subscales
      (intrusion and avoidance) as a screening instrument for PTSD. The questionnaire
      WHOQOL-Bref was used to assess QoL. The WHOQOL-BREF instrument comprises 26
      items, which measure the following broad domains: physical health, psychological
      health, social relationships, and environment. Results of the analysis were
      summarized by fitting Structural Equation Modelling (SEM). RESULTS: For each
      category of PTSD (probable cases, risk level cases and no cases), the mean levels
      of the WHOQOL-Bref subscales (the four domains and the two single items) were
      stable across time of assessment. Individuals who scored as probable PTSD or as
      risk level cases had significantly lower scores on the QoL domains such as
      physical health, psychological health, social relationships and environmental
      than those without PTSD symptoms. In addition, the two items examining perception
      of overall quality of life and perception of overall health in WHOQOL showed the
      same results according to PTSD symptoms such as QoL domains. PTSD symptoms
      predicted lower QoL at all three assessments. Similarly PTSD symptoms at T1
      predicted lower QoL at T2 and PTSD symptoms at T2 predicted lower QoL at T3.
      CONCLUSION: The presence of PTSD symptoms predicted lower QoL, both from an acute
      and prolonged perspective, in victims of non-domestic violence. Focusing on the
      individual's perception of his/her QoL in addition to the illness may increase
      the treatment priorities and efforts.

PMID- 17517127
TI  - A computational survey of candidate exonic splicing enhancer motifs in the model
      plant Arabidopsis thaliana.
AB  - BACKGROUND: Algorithmic approaches to splice site prediction have relied mainly
      on the consensus patterns found at the boundaries between protein coding and non
      coding regions. However exonic splicing enhancers have been shown to enhance the
      utilization of nearby splice sites. RESULTS: We have developed a new
      computational technique to identify significantly conserved motifs involved in
      splice site regulation. First, 84 putative exonic splicing enhancer hexamers are
      identified in Arabidopsis thaliana. Then a Gibbs sampling program called ELPH was
      used to locate conserved motifs represented by these hexamers in exonic regions
      near splice sites in confirmed genes. Oligomers containing 35 of these motifs
      have been shown experimentally to induce significant inclusion of A. thaliana
      exons. Second, integration of our regulatory motifs into two different splice
      site recognition programs significantly improved the ability of the software to
      correctly predict splice sites in a large database of confirmed genes. We have
      released GeneSplicerESE, the improved splice site recognition code, as open
      source software. CONCLUSION: Our results show that the use of the ESE motifs
      consistently improves splice site prediction accuracy.

PMID- 17517128
TI  - Live imaging of Drosophila gonad formation reveals roles for Six4 in regulating
      germline and somatic cell migration.
AB  - BACKGROUND: Movement of cells, either as amoeboid individuals or in organised
      groups, is a key feature of organ formation. Both modes of migration occur during
      Drosophila embryonic gonad development, which therefore provides a paradigm for
      understanding the contribution of these processes to organ morphogenesis. Gonads
      of Drosophila are formed from three distinct cell types: primordial germ cells
      (PGCs), somatic gonadal precursors (SGPs), and in males, male-specific somatic
      gonadal precursors (msSGPs). These originate in distinct locations and migrate to
      associate in two intermingled clusters which then compact to form the spherical
      primitive gonads. PGC movements are well studied, but much less is known of the
      migratory events and other interactions undergone by their somatic partners.
      These appear to move in organised groups like, for example, lateral line cells in
      zebra fish or Drosophila ovarian border cells. RESULTS: We have used time-lapse
      fluorescence imaging to characterise gonadal cell behaviour in wild type and
      mutant embryos. We show that the homeodomain transcription factor Six4 is
      required for the migration of the PGCs and the msSGPs towards the SGPs. We have
      identified a likely cause of this in the case of PGCs as we have found that Six4
      is required for expression of Hmgcr which codes for HMGCoA reductase and is
      necessary for attraction of PGCs by SGPs. Six4 affects msSGP migration by a
      different pathway as these move normally in Hmgcr mutant embryos. Additionally,
      embryos lacking fully functional Six4 show a novel phenotype in which the SGPs,
      which originate in distinct clusters, fail to coalesce to form unified gonads.
      CONCLUSION: Our work establishes the Drosophila gonad as a model system for the
      analysis of coordinated cell migrations and morphogenesis using live imaging and
      demonstrates that Six4 is a key regulator of somatic cell function during
      gonadogenesis. Our data suggest that the initial association of SGP clusters is
      under distinct control from the movements that drive gonad compaction.

PMID- 17517129
TI  - Genetic structure of Plasmodium falciparum field isolates in eastern and north
      eastern India.
AB  - BACKGROUND: Molecular techniques have facilitated the studies on genetic
      diversity of Plasmodium species particularly from field isolates collected
      directly from patients. The msp-1 and msp-2 are highly polymorphic markers and
      the large allelic polymorphism has been reported in the block 2 of the msp-1 gene
      and the central repetitive domain (block3) of the msp-2 gene. Families differing
      in nucleotide sequences and in number of repetitive sequences (length variation)
      were used for genotyping purposes. As limited reports are available on the
      genetic diversity existing among Plasmodium falciparum population of India, this
      report evaluates the extent of genetic diversity in the field isolates of P.
      falciparum in eastern and north-eastern regions of India. METHODS: A study was
      designed to assess the diversity of msp-1 and msp-2 among the field isolates from
      India using allele specific nested PCR assays and sequence analysis. Field
      isolates were collected from five sites distributed in three states namely,
      Assam, West Bengal and Orissa. RESULTS: P. falciparum isolates of the study sites
      are highly diverse in respect of length as well as sequence motifs with
      prevalence of all the reported allelic families of msp-1 and msp-2. Prevalence of
      identical allelic composition as well as high level of sequence identity of
      alleles suggest a considerable amount of gene flow between the P. falciparum
      populations of different states. A comparatively higher proportion of multiclonal
      isolates as well as multiplicity of infection (MOI) was observed among isolates
      of highly malarious districts Karbi Anglong (Assam) and Sundergarh (Orissa). In
      all the five sites, R033 family of msp-1 was observed to be monomorphic with an
      allele size of 150/160 bp. The observed 80-90% sequence identity of Indian
      isolates with data of other regions suggests that Indian P. falciparum population
      is a mixture of different strains. CONCLUSION: The present study shows that the
      field isolates of eastern and north-eastern regions of India are highly diverse
      in respect of msp-1 (block 2) and msp-2 (central repeat region, block 3). As
      expected Indian isolates present a picture of diversity closer to southeast Asia,
      Papua New Guinea and Latin American countries, regions with low to meso
      endemicity of malaria in comparison to African regions of hyper- to holo
      endemicity.

PMID- 17517130
TI  - Hospital-acquired Clostridium difficile-associated disease in the intensive care
      unit setting: epidemiology, clinical course and outcome.
AB  - BACKGROUND: Clostridium difficile-associated disease (CDAD) is a serious
      nosocomial infection, however few studies have assessed CDAD outcome in the
      intensive care unit (ICU). We evaluated the epidemiology, clinical course and
      outcome of hospital-acquired CDAD in the critical care setting. METHODS: We
      performed a historical cohort study on 58 adults with a positive C. difficile
      cytotoxin assay result occurring in intensive care units. RESULTS: Sixty-two
      percent of patients had concurrent infections, 50% of which were bloodstream
      infections. The most frequently prescribed antimicrobials prior to CDAD were anti
      anaerobic agents (60.3%). Septic shock occurred in 32.8% of CDAD patients. The in
      hospital mortality was 27.6%. Univariate analysis revealed that SOFA score, at
      least one organ failure and age were predictors of mortality. Charlson score
      >/=3, gender, concurrent infection, and number of days with diarrhea before a
      positive C. difficile toxin assay were not significant predictors of mortality on
      univariate analysis. Independent predictors for death were SOFA score at
      infection onset (per 1-point increment, OR 1.40; CI95 1.13-1.75) and age (per 1
      year increment, OR 1.10; CI95 1.02-1.19). CONCLUSION: In ICU patients with CDAD,
      advanced age and increased severity of illness at the onset of infection, as
      measured by the SOFA score, are independent predictors of death.

PMID- 17517132
TI  - TISs-ST: a web server to evaluate polymorphic translation initiation sites and
      their reflections on the secretory targets.
AB  - BACKGROUND: The nucleotide sequence flanking the translation initiation codon
      (start codon context) affects the translational efficiency of eukaryotic mRNAs,
      and may indicate the presence of an alternative translation initiation site (TIS)
      to produce proteins with different properties. Multi-targeting may reflect the
      translational variability of these other protein forms. In this paper we present
      a web server that performs computations to investigate the usage of alternative
      translation initiation sites for the synthesis of new protein variants that might
      have different functions. RESULTS: An efficient web-based tool entitled TISs-ST
      (Translation Initiation Sites and Secretory Targets) evaluates putative
      translation initiation sites and indicates the prediction of a signal peptide of
      the protein encoded from this site. The TISs-ST web server is freely available to
      both academic and commercial users and can be accessed at
      http://ipe.cbmeg.unicamp.br/pub/TISs-ST. CONCLUSION: The program can be used to
      evaluate alternative translation initiation site consensus with user-specified
      sequences, based on their composition or on many position weight matrix models.
      TISs-ST provides analytical and visualization tools for evaluating the periodic
      frequency, the consensus pattern and the total information content of a sequence
      data set. A search option allows for the identification of signal peptides from
      predicted proteins using the PrediSi software.

PMID- 17517131
TI  - Cdkn1c (p57Kip2) is the major regulator of embryonic growth within its imprinted
      domain on mouse distal chromosome 7.
AB  - BACKGROUND: Cdkn1c encodes an embryonic cyclin-dependant kinase inhibitor that
      acts to negatively regulate cell proliferation and, in some tissues, to actively
      direct differentiation. This gene, which is an imprinted gene expressed only from
      the maternal allele, lies within a complex region on mouse distal chromosome 7,
      called the IC2 domain, which contains several other imprinted genes. Studies on
      mouse embryos suggest a key role for genomic imprinting in regulating embryonic
      growth and this has led to the proposal that imprinting evolved as a consequence
      of the mismatched contribution of parental resources in mammals. RESULTS: In this
      study, we characterised the phenotype of mice carrying different copy number
      integrations of a bacterial artificial chromosome spanning Cdkn1c. Excess Cdkn1c
      resulted in embryonic growth retardation that was dosage-dependent and also
      responsive to the genetic background. Two-fold expression of Cdkn1c in a subset
      of tissues caused a 10-30% reduction in embryonic weight, embryonic lethality and
      was associated with a reduction in the expression of the potent, non-imprinted
      embryonic growth factor, Igf1. Conversely, loss of expression of Cdkn1c resulted
      in embryos that were 11% heavier with a two-fold increase in Igf1. CONCLUSION: We
      have shown that embryonic growth in mice is exquisitely sensitive to the precise
      dosage of Cdkn1c. Cdkn1c is a maternally expressed gene and our findings support
      the prediction of the parental conflict hypothesis that that the paternal genome
      silences genes that have an inhibitory role in embryonic growth. Within the IC2
      imprinted domain, Cdkn1c encodes the major regulator of embryonic growth and we
      propose that Cdkn1c was the focal point of the selective pressure for imprinting
      of this domain.

PMID- 17517133
TI  - A set of multiplex panels of microsatellite markers for rapid molecular
      characterization of rice accessions.
AB  - BACKGROUND: This study aimed to analyze the efficiency of three new
      microsatellite multiplex panels, which were designed to evaluate a total of 16
      loci of the rice genome, based on single PCR reactions of each panel. A sample of
      548 accessions of traditional upland rice landraces collected in Brazil in the
      last 25 years was genotyped, a database of allelic frequencies was established,
      estimates of genetic parameters were performed and analysis of genetic structure
      of the collection was developed. RESULTS: The three panels yielded a combined
      matching probability of 6.4 x 10-21, polymorphism information content (PIC) of
      0.637, and a combined power of exclusion greater than 99.99%. A few samples
      presented a genetic background of indica rice. The 16 SSR loci produced a total
      of 229 alleles. Gene diversity values averaged 0.667, and PIC values averaged
      0.637. Genetic structure analysis of the collection using a Bayesian approach
      detected three possible major clusters, with an overall FST value of 0.177.
      Important inputs on the knowledge about upland rice germplasm differentiations
      which happened in Brazil in the last few centuries were also achieved and are
      discussed. CONCLUSION: The three multiplex panels described here represent a
      powerful tool for rice genetic analysis, offering a rapid and efficient option
      for rice germplasm characterization. The data gathered demonstrates the
      feasibility of genotyping extensive germplasm collections using panels of
      multiplexed microsatellite markers. It contributes to the advancement of research
      on large scale characterization and management of germplasm banks, as well as
      identification, protection and assessments of genetic relationship of rice
      germplasm.

PMID- 17517136
TI  - Children's physical activity levels during school recess: a quasi-experimental
      intervention study.
AB  - BACKGROUND: Recess provides a daily opportunity for children to engage in
      moderate-to-vigorous (MVPA) and vigorous physical activity (VPA). Limited
      research has investigated the effects of recess-based interventions on physical
      activity using large sample sizes whilst investigating variables that may
      influence the intervention effect. The aim of the study was to investigate the
      short-term effects of a playground markings and physical structures intervention
      on recess physical activity. A secondary aim was to investigate the effects of
      covariates on the intervention. METHODS: 150 boys and 147 girls were randomly
      selected from 26 elementary schools to wear uni-axial accelerometers that
      quantified physical activity every 5 seconds during recess. Fifteen schools
      located in deprived areas in one large urban city in England received funding
      through a national initiative to redesign the playground environment. Eleven
      schools served as matched socioeconomic controls. Data were collected at baseline
      and 6-weeks following playground intervention. Recess MVPA and VPA levels
      adjusted for pupil- and school-level covariates (baseline physical activity, age,
      gender, recess length, body mass index) were analysed using multilevel analyses.
      RESULTS: Positive but non-significant intervention effects were found for MVPA
      and VPA when confounding variables were added to the model. Gender was a
      significant predictor of recess physical activity, with boys engaging in more
      MVPA and VPA than girls. Significant interactions for MVPA revealed that the
      intervention effect was stronger for younger elementary aged school children
      compared to older children, and the intervention effect increased as daily recess
      duration increased. CONCLUSION: The playground redesign intervention resulted in
      small but non-significant increases in children's recess physical activity when
      school and pupil level variables were added to the analyses. Changing the
      playground environment produced a stronger intervention effect for younger
      children, and longer daily recess duration enabled children to engage in more
      MVPA following the intervention. This study concludes that the process of
      increasing recess physical activity is complex when school and pupil-level
      covariates are considered, though they should be taken into account when
      investigating the effects of playground intervention studies on children's
      physical activity during recess.

PMID- 17517134
TI  - Large-scale clustering of CAGE tag expression data.
AB  - BACKGROUND: Recent analyses have suggested that many genes possess multiple
      transcription start sites (TSSs) that are differentially utilized in different
      tissues and cell lines. We have identified a huge number of TSSs mapped onto the
      mouse genome using the cap analysis of gene expression (CAGE) method. The
      standard hierarchical clustering algorithm, which gives us easily understandable
      graphical tree images, has difficulties in processing such huge amounts of TSS
      data and a better method to calculate and display the results is needed. RESULTS:
      We use a combination of hierarchical and non-hierarchical clustering to cluster
      expression profiles of TSSs based on a large amount of CAGE data to profit from
      the best of both methods. We processed the genome-wide expression data, including
      159,075 TSSs derived from 127 RNA samples of various organs of mouse, and
      succeeded in categorizing them into 70-100 clusters. The clusters exhibited
      intriguing biological features: a cluster supergroup with a ubiquitous expression
      profile, tissue-specific patterns, a distinct distribution of non-coding RNA and
      functional TSS groups. CONCLUSION: Our approach succeeded in greatly reducing the
      calculation cost, and is an appropriate solution for analyzing large-scale TSS
      usage data.

PMID- 17517137
TI  - Validation of the Cognitive Assessment of Later Life Status (CALLS) instrument: a
      computerized telephonic measure.
AB  - BACKGROUND: Brief screening tests have been developed to measure cognitive
      performance and dementia, yet they measure limited cognitive domains and often
      lack construct validity. Neuropsychological assessments, while comprehensive, are
      too costly and time-consuming for epidemiological studies. This study's aim was
      to develop a psychometrically valid telephone administered test of cognitive
      function in aging. METHODS: Using a sequential hierarchical strategy, each stage
      of test development did not proceed until specified criteria were met. The 30
      minute Cognitive Assessment of Later Life Status (CALLS) measure and a 2.5 hour
      in-person neuropsychological assessment were conducted with a randomly selected
      sample of 211 participants 65 years and older that included equivalent
      distributions of men and women from ethnically diverse populations. RESULTS:
      Overall Cronbach's coefficient alpha for the CALLS test was 0.81. A principal
      component analysis of the CALLS tests yielded five components. The CALLS total
      score was significantly correlated with four neuropsychological assessment
      components. Older age and having a high school education or less was
      significantly correlated with lower CALLS total scores. Females scored better
      overall than males. There were no score differences based on race. CONCLUSION:
      The CALLS test is a valid measure that provides a unique opportunity to reliably
      and efficiently study cognitive function in large populations.

PMID- 17517138
TI  - A Turner syndrome neurocognitive phenotype maps to Xp22.3.
AB  - BACKGROUND: Turner syndrome (TS) is associated with a neurocognitive phenotype
      that includes selective nonverbal deficits, e.g., impaired visual-spatial
      abilities. We previously reported evidence that this phenotype results from
      haploinsufficiency of one or more genes on distal Xp. This inference was based on
      genotype/phenotype comparisons of individual girls and women with partial Xp
      deletions, with the neurocognitive phenotype considered a dichotomous trait. We
      sought to confirm our findings in a large cohort (n = 47) of adult women with
      partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions.
      METHODS: Subjects were recruited from North American genetics and endocrinology
      clinics. Phenotype assessment included measures of stature, ovarian function, and
      detailed neurocognitive testing. The neurocognitive phenotype was measured as a
      quantitative trait, the Turner Syndrome Cognitive Summary (TSCS) score, derived
      from discriminant function analysis. Genetic analysis included karyotyping, X
      inactivation studies, fluorescent in situ hybridization, microsatellite marker
      genotyping, and array comparative genomic hybridization. RESULTS: We report
      statistical evidence that deletion of Xp22.3, an interval containing 31 annotated
      genes, is sufficient to cause the neurocognitive phenotype described by the TSCS
      score. Two other cardinal TS features, ovarian failure and short stature, as well
      as X chromosome inactivation pattern and subject's age, were unrelated to the
      TSCS score. CONCLUSION: Detailed mapping suggests that haploinsufficiency of one
      or more genes in Xp22.3, the distal 8.3 megabases (Mb) of the X chromosome, is
      responsible for a TS neurocognitive phenotype. This interval includes the 2.6 Mb
      Xp-Yp pseudoautosomal region (PAR1). Haploinsufficiency of the short stature gene
      SHOX in PAR1 probably does not cause this TS neurocognitive phenotype. Two genes
      proximal to PAR1 within the 8.3 Mb critical region, STS and NLGN4X, are
      attractive candidates for this neurocognitive phenotype.

PMID- 17517139
TI  - Robust detection and verification of linear relationships to generate metabolic
      networks using estimates of technical errors.
AB  - BACKGROUND: The size and magnitude of the metabolome, the ratio between
      individual metabolites and the response of metabolic networks is controlled by
      multiple cellular factors. A tight control over metabolite ratios will be
      reflected by a linear relationship of pairs of metabolite due to the flexibility
      of metabolic pathways. Hence, unbiased detection and validation of linear
      metabolic variance can be interpreted in terms of biological control. For robust
      analyses, criteria for rejecting or accepting linearities need to be developed
      despite technical measurement errors. The entirety of all pair wise linear
      metabolic relationships then yields insights into the network of cellular
      regulation. RESULTS: The Bayesian law was applied for detecting linearities that
      are validated by explaining the residues by the degree of technical measurement
      errors. Test statistics were developed and the algorithm was tested on simulated
      data using 3-150 samples and 0-100% technical error. Under the null hypothesis of
      the existence of a linear relationship, type I errors remained below 5% for data
      sets consisting of more than four samples, whereas the type II error rate quickly
      raised with increasing technical errors. Conversely, a filter was developed to
      balance the error rates in the opposite direction. A minimum of 20 biological
      replicates is recommended if technical errors remain below 20% relative standard
      deviation and if thresholds for false error rates are acceptable at less than 5%.
      The algorithm was proven to be robust against outliers, unlike Pearson's
      correlations. CONCLUSION: The algorithm facilitates finding linear relationships
      in complex datasets, which is radically different from estimating linearity
      parameters from given linear relationships. Without filter, it provides high
      sensitivity and fair specificity. If the filter is activated, high specificity
      but only fair sensitivity is yielded. Total error rates are more favorable with
      deactivated filters, and hence, metabolomic networks should be generated without
      the filter. In addition, Bayesian likelihoods facilitate the detection of
      multiple linear dependencies between two variables. This property of the
      algorithm enables its use as a discovery tool and to generate novel hypotheses of
      the existence of otherwise hidden biological factors.

PMID- 17517140
TI  - AT excursion: a new approach to predict replication origins in viral genomes by
      locating AT-rich regions.
AB  - BACKGROUND: Replication origins are considered important sites for understanding
      the molecular mechanisms involved in DNA replication. Many computational methods
      have been developed for predicting their locations in archaeal, bacterial and
      eukaryotic genomes. However, a prediction method designed for a particular kind
      of genomes might not work well for another. In this paper, we propose the AT
      excursion method, which is a score-based approach, to quantify local AT abundance
      in genomic sequences and use the identified high scoring segments for predicting
      replication origins. This method has the advantages of requiring no preset window
      size and having rigorous criteria to evaluate statistical significance of high
      scoring segments. RESULTS: We have evaluated the AT excursion method by checking
      its predictions against known replication origins in herpesviruses and comparing
      its performance with an existing base weighted score method (BWS1). Out of 43
      known origins, 39 are predicted by either one or the other method and 26 origins
      are predicted by both. The excursion method identifies six origins not predicted
      by BWS1, showing that the AT excursion method is a valuable complement to BWS1.
      We have also applied the AT excursion method to two other families of double
      stranded DNA viruses, the poxviruses and iridoviruses, of which very few
      replication origins are documented in the public domain. The prediction results
      are made available as supplementary materials at 1. Preliminary investigation
      shows that the proposed method works well on some larger genomes too. CONCLUSION:
      The AT excursion method will be a useful computational tool for identifying
      replication origins in a variety of genomic sequences.

PMID- 17517141
TI  - Quantification of malaria parasite release from infected erythrocytes: inhibition
      by protein-free media.
AB  - BACKGROUND: Intracellular malaria parasites leave their host erythrocytes to
      infect neighbouring cells after each cycle of asexual replication. No method is
      currently available for the direct quantification of parasite release. METHOD AND
      RESULTS: To quantify parasite release process, human erythrocytes infected with
      Plasmodium falciparum were injected into sealed chambers at optimal density,
      where they progressed through the end of the erythrocyte cycle. Each event of
      parasite release inside the chamber at the site of erythrocyte rupture leaves on
      the chamber wall a footprint, composed of 1) separated parasites, 2) a digestive
      vacuole with haemozoin, and 3) fragments of the ruptured membranes. These
      footprints are stable for hours, allowing precise identification using
      differential interference contrast (DIC) microscopy. The relative rate of
      parasite release is defined as the percent of such footprints out of all
      schizonts injected and incubated into chamber at 37 degrees C for two hours. The
      method is highly reproducible, easy to perform, and does not require expensive
      equipment. Additionally, this method allows one to analyse cell and release site
      morphology, which adds information about the release process and the quality of
      the culture. The method is used here to show that swelling of schizonts caused by
      protein-free media inhibits parasite release. CONCLUSION: In this study, a novel
      method is described to count sites of parasite release by microscopy. Besides the
      direct estimation of parasite release from infected erythrocytes, this method
      provides a morphological evaluation of normal infected cells approaching the end
      of the plasmodial life cycle, or pathological forms accumulated as the result of
      experimental intervention in the parasite release process. One may now accurately
      estimate the relative parasite release rate at the time of cycle transition,
      without any obligatory coupling to parasite invasion.

PMID- 17517142
TI  - Endogenous pararetroviral sequences in tomato (Solanum lycopersicum) and related
      species.
AB  - BACKGROUND: Endogenous pararetroviral sequences (EPRVs) are a recently discovered
      class of repetitive sequences that is broadly distributed in the plant kingdom.
      The potential contribution of EPRVs to plant pathogenicity or, conversely, to
      virus resistance is just beginning to be explored. Some members of the family
      Solanaceae are particularly rich in EPRVs. In previous work, EPRVs have been
      characterized molecularly in various species of Nicotiana including N.tabacum
      (tobacco) and Solanum tuberosum (potato). Here we describe a family of EPRVs in
      cultivated tomato (Solanum lycopersicum L.) and a wild relative (S.habrochaites).
      RESULTS: Molecular cloning and DNA sequence analysis revealed that tomato EPRVs
      (named LycEPRVs) are most closely related to those in tobacco. The sequence
      similarity of LycEPRVs in S.lycopersicum and S.habrochaites indicates they are
      potentially derived from the same pararetrovirus. DNA blot analysis revealed a
      similar genomic organization in the two species, but also some independent
      excision or insertion events after species separation, or flanking sequence
      divergence. LycEPRVs share with the tobacco elements a disrupted genomic
      structure and frequent association with retrotransposons. Fluorescence in situ
      hybridization revealed that copies of LycEPRV are dispersed on all chromosomes in
      predominantly heterochromatic regions. Methylation of LycEPRVs was detected in
      CHG and asymmetric CHH nucleotide groups. Although normally quiescent EPRVs can
      be reactivated and produce symptoms of infection in some Nicotiana interspecific
      hybrids, a similar pathogenicity of LycEPRVs could not be demonstrated in Solanum
      L. section Lycopersicon [Mill.] hybrids. Even in healthy plants, however,
      transcripts derived from multiple LycEPRV loci and short RNAs complementary to
      LycEPRVs were detected and were elevated upon infection with heterologous viruses
      encoding suppressors of PTGS. CONCLUSION: The analysis of LycEPRVs provides
      further evidence for the extensive invasion of pararetroviral sequences into the
      genomes of solanaceous plants. The detection of asymmetric CHH methylation and
      short RNAs, which are hallmarks of RNAi in plants, suggests that LycEPRVs are
      controlled by an RNA-mediated silencing mechanism.

PMID- 17517143
TI  - The promoter and transcribed regions of the Leishmania tarentolae spliced leader
      RNA gene array are devoid of nucleosomes.
AB  - BACKGROUND: The spliced leader (SL) RNA provides the 5' m7G cap and first 39 nt
      for all nuclear mRNAs in kinetoplastids. This small nuclear RNA is transcribed by
      RNA polymerase II from individual promoters. In Leishmania tarentolae the SL RNA
      genes reside in two multi-copy tandem arrays designated MINA and MINB. The
      transcript accumulation from the SL promoter on the drug-selected, episomal SL
      RNA gene cassette pX-tSL is ~10% that of the genomic array in uncloned L.
      tarentolae transfectants. This disparity is neither sequence- nor copy-number
      related, and thus may be due to interference of SL promoter function by
      epigenetic factors. To explore these possibilities we examined the nucleoplasmic
      localization of the SL RNA genes as well as their nucleosomal architecture.
      RESULTS: The genomic SL RNA genes and the episome did not co-localize within the
      nucleus. Each genomic repeat contains one nucleosome regularly positioned within
      the non-transcribed intergenic region. The 363-bp MINA array was resistant to
      micrococcal nuclease digestion between the -258 and -72 positions relative to the
      transcription start point due to nucleosome association, leaving the promoter
      elements and the entire transcribed region exposed for protein interactions. A
      pattern of ~164-bp protected segments was observed, corresponding to the amount
      of DNA typically bound by a nucleosome. By contrast, nucleosomes on the pX-tSL
      episome were randomly distributed over the episomal SL cassette, reducing
      transcription factor access to the episomal promoter by approximately 74%.
      Cloning of the episome transfectants revealed a range of transcriptional
      activities, implicating a mechanism of epigenetic heredity. CONCLUSION: The
      disorganized nucleosomes on the pX episome are in a permissive conformation for
      transcription of the SL RNA cassette approximately 25% of the time within a given
      parasite. Nucleosome interference is likely the major factor in the apparent
      transcriptional repression of the SL RNA gene cassette. Coupled with the
      requirement for run-around transcription that drives expression of the selectable
      drug marker, transcription of the episomal SL may be reduced even further due to
      sub-optimal nucleoplasmic localization and initiation complex disruption.

PMID- 17517145
TI  - A novel mutation in the WFS1 gene identified in a Taiwanese family with low
      frequency hearing impairment.
AB  - BACKGROUND: Wolfram syndrome gene 1 (WFS1) accounts for most of the familial
      nonsyndromic low-frequency sensorineural hearing loss (LFSNHL) which is
      characterized by sensorineural hearing losses equal to and below 2000 Hz. The
      current study aimed to contribute to our understanding of the molecular basis of
      LFSNHL in an affected Taiwanese family. METHODS: The Taiwanese family with LFSNHL
      was phenotypically characterized using audiologic examination and pedigree
      analysis. Genetic characterization was performed by direct sequencing of WFS1 and
      mutation analysis. RESULTS: Pure tone audiometry confirmed that the family
      members affected with LFSNHL had a bilateral sensorineural hearing loss equal to
      or below 2000 Hz. The hearing loss threshold of the affected members showed no
      progression, a characteristic that was consistent with a mutation in the WFS1
      gene located in the DFNA6/14/38 locus. Pedigree analysis showed a hereditarily
      autosomal dominant pattern characterized by a full penetrance. Among several
      polymorphisms, a missense mutation Y669H (2005T>C) in exon 8 of WFS1 was
      identified in members of a Taiwanese family diagnosed with LFSNHL but not in any
      of the control subjects. CONCLUSION: We discovered a novel heterozygous missense
      mutation in exon 8 of WFS1 (i.e., Y669H) which is likely responsible for the
      LFSNHL phenotype in this particular Taiwanese family.

PMID- 17517144
TI  - The chemokine Sdf-1 and its receptor Cxcr4 are required for formation of muscle
      in zebrafish.
AB  - BACKGROUND: During development cell migration takes place prior to
      differentiation of many cell types. The chemokine receptor Cxcr4 and its ligand
      Sdf1 are implicated in migration of several cell lineages, including appendicular
      muscles. RESULTS: We dissected the role of sdf1-cxcr4 during skeletal myogenesis.
      We demonstrated that the receptor cxcr4a is expressed in the medial-anterior part
      of somites, suggesting that chemokine signaling plays a role in this region of
      the somite. Previous reports emphasized co-operation of Sdf1a and Cxcr4b. We
      found that during early myogenesis Sdf1a co-operates with the second Cxcr4 of
      zebrafish - Cxcr4a resulting in the commitment of myoblast to form fast muscle.
      Disrupting this chemokine signal caused a reduction in myoD and myf5 expression
      and fast fiber formation. In addition, we showed that a dimerization partner of
      MyoD and Myf5, E12, positively regulates transcription of cxcr4a and sdf1a in
      contrast to that of Sonic hedgehog, which inhibited these genes through induction
      of expression of id2. CONCLUSION: We revealed a regulatory feedback mechanism
      between cxcr4a-sdf1a and genes encoding myogenic regulatory factors, which is
      involved in differentiation of fast myofibers. This demonstrated a role of
      chemokine signaling during development of skeletal muscles.

PMID- 17517146
TI  - Quantifying the economic burden of malaria in Nigeria using the willingness to
      pay approach.
AB  - BACKGROUND: Malaria illness imposes great burden on the society as it has adverse
      effects on the physical, mental and social well being of the people as well as on
      the economic development of the nation. METHODS: The study uses the Willingness
      To Pay (WTP) approach to evaluate the burden of malaria in Nigeria. RESULTS: The
      results indicate that households would be prepared to pay an average of about
      Naira 1,112 (USD 9.3) per month for the treatment of malaria. This is about Naira
      427 (USD 3.6) in excess of the average expenditure they currently make on malaria
      treatment per month. Similarly, households are willing to pay on the average a
      sum of Naira 7,324 (USD 61) per month for the control of malaria. Again, this is
      an excess of about Naira 2,715 (USD 22.6) over the cost they currently bear
      (protection, treatment and indirect costs), and it represents households' average
      valuation of their intangible costs of malaria illness. This amount represents
      about Naira 611.7 (USD 5.1) per head per month and Naira 7,340 (USD 61.2) per
      year. For a country with a population of about 120 million this translates to
      about Naira 880,801 million per annum representing about 12.0 per cent of Gross
      Domestic Product. Hence, the malaria burden in Nigeria is enormous and has a
      devastating impact on economic growth. CONCLUSION: In the long term, it is
      important to recognize that health and poverty are closely linked. Reducing the
      burden of malaria in Nigeria will help to contribute to the economic well-being
      of communities; and poverty-reduction will be an essential input into improving
      health. National malaria control programme in Nigeria and their partners need to
      recognize these links, and identify mechanisms for ensuring that the poorest have
      access to essential health interventions.

PMID- 17517148
TI  - Emotional facial expression in Parkinson's disease: a response to Bowers (2006).

PMID- 17517147
TI  - Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation.
AB  - BACKGROUND: Paroxysms are recurrent febrile episodes, characteristic of
      Plasmodium vivax infections, which coincide with the rupture of schizont-infected
      erythrocytes in the patients' circulation. The present study describes the
      formation of prominent aggregates of leukocytes in vitro in the presence of
      parasite and host factors released during paroxysms. METHODS: Whole blood cells
      from uninfected malaria-naive donors were incubated with plasma taken during a
      paroxysm or normal human plasma as a control and cell smears were observed under
      the microscope for the presence of leukocyte aggregates. Plasma factors involved
      in mediating the leukocyte aggregation were identified using immune depletion and
      reconstitution experiments. Furthermore, biochemical characterization was carried
      out to determine the chemical nature of the active moieties in plasma present
      during paroxysms. RESULTS: Leukocyte aggregates were seen exclusively when cells
      were incubated in plasma collected during a paroxysm. Immune depletion and
      reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL
      6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and
      sufficient mediators of this phenomenon. The two lipid components of the paroxysm
      plasmas speculated to be of putative parasite origin, were a phospholipid
      containing fraction and another containing cholesterol and triglycerides. The
      phospholipid fraction was dependent upon the presence of cytokines for its
      activity unlike the cholesterol/triglyceride-containing fraction which in the
      absence of added cytokines was much more active than the phospholipids fraction.
      The biological activity of the paroxysm plasmas from non-immune patients who
      presented with acute P. vivax infections was neutralized by immune sera raised
      against schizont extracts of either P. vivax or Plasmodium falciparum. However,
      immune sera against P. vivax were more effective than that against P. falciparum
      indicating that the parasite activity involved may be antigenically at least
      partially parasite species-specific. CONCLUSION: Leukocyte aggregation was
      identified as associated with paroxysms in P. vivax infections. This phenomenon
      is mediated by plasma factors including host-derived cytokines and lipids of
      putative parasite origin. The characteristics of the phospholipid fraction in
      paroxysm plasma are congruent with those of the parasite-derived, TNF-inducing
      GPI moieties described by others. The more active cholesterol/triglyceride(s),
      however, represent a novel malarial toxin, which is a new class of biologically
      active lipid associated with the paroxysm of P. vivax malaria.

PMID- 17517149
TI  - Differential effect of catechol-O-methyltransferase Val158Met genotype on
      emotional recognition abilities in healthy men and women.
AB  - The catechol-O-methyltransferase (COMT) Val158Met polymorphism modulates
      executive functions and working memory and recent neuroimaging studies implicate
      an association with emotional processing. We examined the relationship between
      the COMT Val158Met polymorphism and facial emotion recognition and
      differentiation in 100 healthy individuals. Compared to Met homozygosity, Val
      homozygosity was associated with better and faster recognition of negative facial
      expressions such as anger and sad. Our study provides evidence for a possible
      influence of the COMT polymorphism on emotion recognition abilities in healthy
      subjects. Additional research is needed to further define the neurocognitive
      phenotypes associated with COMT polymorphisms.

PMID- 17517150
TI  - Early experience with remote pressure sensor respiratory plethysmography
      monitoring sedation in the MR scanner.
AB  - BACKGROUND AND OBJECTIVE: The importance of monitoring the breathing pattern
      during sedation of children undergoing magnetic resonance scans is indicated in
      guidelines, but no appropriate magnetic resonance-compatible devices are
      available. We report preliminary findings from a technique referred to as remote
      pressure sensor respiratory plethysmography. METHODS: A data acquisition system
      was developed, enabling measurement of respiratory rate, plethysmogram amplitude,
      proportion of inspiratory time over cycle time, thoraco-abdominal phase shift and
      sigh rate. Correlation between plethysmogram amplitude and tidal volume was
      investigated on adult volunteers. Twenty-seven children undergoing sedation were
      monitored with remote pressure sensor respiratory plethysmography, in addition to
      SPO2 and PetCO2. Differences in monitoring parameters were searched for among
      three groups: patients who received chloral hydrate only (chloral succeeded, CS
      group), those who received a supplementation of sodium thiopental (chloral
      failed, CF group), and those who were sedated with sodium thiopental directly (no
      chloral, NC group). Correlations were searched for among monitoring parameters,
      and with total dose of thiopental. The long-term behaviour of respiratory rate,
      proportion of inspiratory time over cycle time and phase shift was studied.
      RESULTS: Plethysmogram amplitude was found to correlate linearly with tidal
      volume (r>0.92), with a slope varying up to 22%. While 11% of patients did not
      tolerate the capnometric probe and readings were discontinuous in 26%, all of
      them tolerated remote pressure sensor respiratory plethysmography belts. Sighs
      and non-respiratory movements of the torso could be distinguished on remote
      pressure sensor respiratory plethysmography waveforms. No significant inter-group
      differences were found in PetCO2, SPO2, respiratory rate and phase shift.
      Proportion of inspiratory time over cycle time was higher in the NC group when
      compared to the CS group (0.497+/-0.03 vs. 0.463+/-0.008; P=0.02), the CF group
      being characterized by intermediate values (0.480+/-0.008); when compared to the
      CS group, sigh rate was lower in the CF group (0.04+/-0.04 vs. 0.14+/-0.08;
      P=0.04) and in the NC group (0.06+/-0.05 vs. 0.14+/-0.08, P=0.03). A positive
      correlation was found between total dose of thiopental and proportion of
      inspiratory time over cycle time, with r=0.4 and P=0.04. A large baseline
      variability in phase shift was found. No long-term trends predictive of patient
      movement could be identified. CONCLUSIONS: Breathing pattern monitoring is
      feasible through pneumatic devices, which are well tolerated. The resulting
      correlation with changes in tidal volume can be better when compared to visual
      inspection. Proportion of inspiratory time over cycle time and sigh rate convey
      information related to the state of the sedated patient. These results are not
      specific to the technology employed, and large-scale studies on the clinical
      usefulness of breathing pattern monitoring are motivated.

PMID- 17517151
TI  - Dietary behaviour of Tehranian adolescents does not accord with their nutritional
      knowledge.
AB  - OBJECTIVE: To determine the nutritional behaviour of Tehranian adolescents.
      SUBJECTS AND METHODS: This study was undertaken on 7669 adolescents (4070 boys
      and 3599 girls) of 22 junior high schools and high schools as a representative
      sample of Tehranian adolescents. A validated knowledge, attitudes and practices
      (KAP) questionnaire and a food-frequency questionnaire (FFQ) were used. Factor
      analysis was used to determine the key questions. RESULTS: The mean ( +/-
      standard deviation) age and body mass index of the adolescents was 14 +/- 1 years
      and 27.2 +/- 11 kg m- 2. Although 82% of girls and 75% of boys had good
      nutritional knowledge, only 25% of boys and 15% of girls had good nutritional
      practice. Eighty-five per cent of adolescents knew that drinking too many soft
      beverages resulted in overweight or obesity, but only 4.5% of them did not drink
      soft beverages. Although 89% of adolescents knew that crisps and corn balls are
      not healthy snacks, 45% of them used such snacks during their break time. Thirty
      seven per cent of adolescents preferred whole-grain biscuits to creamy wafer ones
      but only 10% of adolescents used whole-grain biscuits as a snack. The most
      frequently consumed snacks among Tehranian adolescents were sausage sandwiches,
      cocoa cola, crisps and corn balls, creamy wafers, cakes, chocolate and toffee.
      CONCLUSION: A low percentage of Tehranian adolescents have good nutritional
      behaviour and in most of them their nutritional practice does not accord with
      their nutritional knowledge. These results indicate the necessity of nutritional
      intervention in Tehranian adolescents.

PMID- 17517152
TI  - Breast-feeding mothers can exercise: results of a cohort study.
AB  - OBJECTIVES: To study the relationship between exercise by the mother and breast
      feeding initiation and duration, and its effect on infant growth. DESIGN: A
      cohort study of mothers and infants, recruited at birth. Infant feeding methods
      were recorded in detail and breast-feeding was categorised as 'any' or 'full'.
      Exercise levels were categorised using the metabolic equivalent tasks approach
      based on details of physical activity recorded in questionnaires. SETTING: Perth,
      Western Australia. SUBJECTS: A total of 587 mothers were interviewed on seven
      occasions over a period of 12 months. RESULTS: There was no difference in the
      means of infant weight and length changes, indicating that exercise appeared to
      have no significant influence on infant growth up to 52 weeks after birth
      (P=0.236 and 0.974, respectively). The mother's level of exercise was not
      significantly associated with breast-feeding to 6 or 12 months. This applied to
      'full' and 'any' categories of breast-feeding. CONCLUSION: Exercise does not
      affect breast-feeding outcomes at the usual levels of activity undertaken by
      mothers. Breast-feeding and exercise are important for maintaining and promoting
      health, and this study provides reassurance to health professionals wishing to
      encourage mothers to continue both behaviours.

PMID- 17517153
TI  - Magazines for children and young people and the links to Internet food marketing:
      a review of the extent and type of food advertising.
AB  - OBJECTIVE: To examine the nature of the link between food advertising in UK
      magazines aimed at children and young people and Internet food marketing, to
      establish whether consideration should be given to tightening existing controls.
      DESIGN: A review and descriptive analysis of food advertising found in a sample
      of the top five magazine titles aimed at a range of ages of children and young
      people between November 2004 and August 2005 and of the Internet food marketing
      sites to which readers were directed. RESULTS: Food advertising appeared as
      'cover-mount' free gifts and as part of the main bound issue. Children aged 6-10
      years were the most frequent recipients of food-based free gifts, all of which
      were confectionery. No food advertising was found in magazines aimed at pre
      school children and it formed a small percentage of total advertising in the
      magazines aimed at children of school age and above. Most food advertisements
      were for 'less healthy' foods, although advertisements for 'healthier' food
      products did appear infrequently. Almost half of food advertisements directed
      readers towards Internet food marketing sites. We found evidence that these sites
      are using at least some of the 'marketing tricks' which have been identified as a
      cause for concern. CONCLUSIONS: Proposed restrictions on broadcast media may lead
      to more food advertising via other non-broadcast means. We suggest monitoring the
      effect of such changes in print and online advertising and that consideration be
      given to restricting marketing techniques used on websites aimed at children and
      young people.

PMID- 17517154
TI  - Evaluation of linkage disequilibrium measures between multi-allelic markers as
      predictors of linkage disequilibrium between single nucleotide polymorphisms.
AB  - Effectiveness of marker-assisted selection (MAS) and quantitative trait locus
      (QTL) mapping using population-wide linkage disequilibrium (LD) between markers
      and QTLs depends on the extent of LD and how it declines with distance between
      markers and QTLs in a population. Marker-QTL LD can be predicted from LD between
      markers. Our previous work evaluated LD measures between multi-allelic markers as
      predictors of usable LD of multi-allelic markers with QTLs. Since single
      nucleotide polymorphisms (SNPs) are the current marker of choice for high-density
      genotyping and LD-mapping of QTLs, the objective of this study was to use LD
      between multi-allelic markers to predict LD among biallelic SNPs or between SNPs
      and QTLs. Observable LD between multi-allelic markers was evaluated using nine
      measures. These included two pooled and standardized measures of LD between pairs
      of alleles at two markers based on Lewontin's LD measure, two pooled measures of
      squared correlations between alleles, one standardized measure using Hardy
      Weinberg heterozygosities, and four measures based on the chi-square statistic
      for testing for association between alleles at two loci. The standardized chi
      square measure that best predicted usable LD between multi-allelic markers and
      QTLs, based on our previous work, overestimated usable SNP-SNP or SNP-QTL LD.
      Instead, three other measures were found to be good predictors of usable SNP-SNP
      or SNP-QTL LD when LD is generated by drift. Therefore, the LD measure between
      multi-allelic markers that is best for predicting usable LD in a population
      depends on the type of markers (i.e. multi-allelic or biallelic) that will
      eventually be used for QTL mapping or MAS.

PMID- 17517155
TI  - Small-world networks decrease the speed of Muller's ratchet.
AB  - Muller's ratchet is an evolutionary process that has been implicated in the
      extinction of asexual species, the evolution of non-recombining genomes, such as
      the mitochondria, the degeneration of the Y chromosome, and the evolution of sex
      and recombination. Here we study the speed of Muller's ratchet in a spatially
      structured population which is subdivided into many small populations (demes)
      connected by migration, and distributed on a graph. We studied different types of
      networks: regular networks (similar to the stepping-stone model), small-world
      networks and completely random graphs. We show that at the onset of the small
      world network - which is characterized by high local connectivity among the demes
      but low average path length - the speed of the ratchet starts to decrease
      dramatically. This result is independent of the number of demes considered, but
      is more pronounced the larger the network and the stronger the deleterious effect
      of mutations. Furthermore, although the ratchet slows down with increasing
      migration between demes, the observed decrease in speed is smaller in the
      stepping-stone model than in small-world networks. As migration rate increases,
      the structured populations approach, but never reach, the result in the
      corresponding panmictic population with the same number of individuals. Since
      small-world networks have been shown to describe well the real contact networks
      among people, we discuss our results in the light of the evolution of microbes
      and disease epidemics.

PMID- 17517156
TI  - A structural mixed model for variances in differential gene expression studies.
AB  - The importance of variance modelling is now widely known for the analysis of
      microarray data. In particular the power and accuracy of statistical tests for
      differential gene expressions are highly dependent on variance modelling. The aim
      of this paper is to use a structural model on the variances, which includes a
      condition effect and a random gene effect, and to propose a simple estimation
      procedure for these parameters by working on the empirical variances. The
      proposed variance model was compared with various methods on both real and
      simulated data. It proved to be more powerful than the gene-by-gene analysis and
      more robust to the number of false positives than the homogeneous variance model.
      It performed well compared with recently proposed approaches such as SAM and
      VarMixt even for a small number of replicates, and performed similarly to Limma.
      The main advantage of the structural model is that, thanks to the use of a linear
      mixed model on the logarithm of the variances, various factors of variation can
      easily be incorporated in the model, which is not the case for previously
      proposed empirical Bayes methods. It is also very fast to compute and is adapted
      to the comparison of more than two conditions.

PMID- 17517157
TI  - Functional mapping of reaction norms to multiple environmental signals.
AB  - Whether there are different genes involved in response to different environmental
      signals and how these genes interact to determine the final expression of the
      trait are of fundamental importance in agricultural and biological research. We
      present a statistical framework for mapping environment-induced genes (or
      quantitative trait loci, QTLs) of major effects on the expression of a trait that
      respond to changing environments. This framework is constructed with a maximum
      likelihood-based mixture model, in which the mean and covariance structure of
      environment-induced responses is modelled. The means for responses to continuous
      environmental states, referred to as reaction norms, are approximated for
      different QTL genotypes by mathematical equations that were derived from
      fundamental biological principles or based on statistical goodness-of-fit to
      observational data. The residual covariance between different environmental
      states was modelled by autoregressive processes. Such an approach to studying the
      genetic control of reaction norms can be expected to be advantageous over
      traditional mapping approaches in which no biological principles and statistical
      structures are considered. We demonstrate the analytical procedure and power of
      this approach by modelling the photosynthetic rate process as a function of
      temperature and light irradiance. Our approach allows for testing how a QTL
      affects the reaction norm of photosynthetic rate to a specific environment and
      whether there exist different QTLs to mediate photosynthetic responses to
      temperature and light irradiance, respectively.

PMID- 17517158
TI  - Gametogenesis of intergroup hybrids of hemiclonal frogs.
AB  - European water frog hybrids Rana esculenta (R. ridibundaxR. lessonae) reproduce
      hemiclonally, by hybridogenesis: in the germ line they exclude the genome of one
      parental species and produce haploid gametes with an unrecombined genome of the
      other parental species. In the widespread L-E population system, both sexes of
      hybrids (E) coexist with R. lessonae (L). They exclude the lessonae genome and
      produce ridibunda gametes. In the R-E system, hybrid males coexist with R.
      ridibunda (R); they exclude either their ridibunda or their lessonae genome and
      produce sperm with a lessonae or with a ridibunda genome or a mixture of both
      kinds of sperm. We examined 13 male offspring, 12 of which were from crosses
      between L-E system and R-E system frogs. All were somatically hybrid. With one
      exception, they excluded the lessonae genome in the germ line and subsequently
      endoreduplicated the ridibunda genome. Spermatogonial metaphases contained a
      haploid or a diploid number of ridibunda chromosomes, identified through in situ
      hybridization to a satellite DNA marker, and by spermatocyte I metaphases
      containing a haploid number of ridibunda bivalents. The exception, an F1 hybrid
      between L-E system R. lessonae and R-E system R. ridibunda, was not
      hybridogenetic, showed no genome exclusion, and evidenced a disturbed
      gametogenesis resulting from the combination of two heterospecific genomes. None
      of the hybridogenetic hybrids showed any cell lines excluding the ridibunda
      genome, the pattern most frequent in hybrids of the R-E system, unique to that
      system, and essential for its persistence. A particular combination of R-E system
      lessonae and R-E system ridibunda genomes seems necessary to induce the R-E
      system type of hemiclonal gametogenesis.

PMID- 17517159
TI  - Multiple-trait QTL mapping for body and organ weights in a cross between NMRI8
      and DBA/2 mice.
AB  - Multiple-trait analyses have been shown to improve the detection of quantitative
      trait loci (QTLs) with multiple effects. Here we applied a multiple-trait
      approach on obesity- and growth-related traits that were surveyed in 275 F2 mice
      generated from an intercross between the high body weight selected line NMRI8 and
      DBA/2 as lean control. The parental lines differed 2.5-fold in body weight at the
      age of 6 weeks. Within the F2 population, the correlations between body weight
      and weights of abdominal fat weight, muscle, liver and kidney at the age of 6
      weeks were about 0.8. A least squares multiple-trait QTL analysis was performed
      on these data to understand more precisely the cause of the genetic correlation
      between body weight, body composition traits and weights of inner organs. Regions
      on Chr 1, 2, 7 and 14 for body weights at different early ages and regions on Chr
      1, 2, 4, 7, 14, 17 and 19 for organ weights at 6 weeks were found to have
      significant multiple effects at the genome-wide level.

PMID- 17517160
TI  - Auditory cortical activation and speech perception in cochlear implant users.
AB  - Cochlear implantation is generally accepted as a successful means of restoring
      auditory sensation to profoundly deaf individuals. Although most patients can
      expect a satisfactory outcome following implantation, some have poor speech
      perception outcomes. This investigation used [18F]-fluorodeoxyglucose positron
      emission tomography to measure cortical activity resulting from auditory
      stimulation in seven 'good' and four 'poor' cochlear implant recipients.
      Activations were significantly greater in both the primary and association
      cortices in the good compared with the poor implant users. We suggest that the
      ability to access the more specialised speech processing abilities of the
      auditory association cortices helps determine outcome following cochlear
      implantation.

PMID- 17517161
TI  - Buccinator myomucosal flap: clinical results and review of anatomy, surgical
      technique and applications.
AB  - BACKGROUND: The buccinator musculomucosal flap is an axial-pattern flap based on
      either the buccal or the facial artery. We present our experience with this flap
      and describe its surgical anatomy, the surgical techniques utilised to raise the
      flap and its clinical applications. MATERIALS AND METHODS: We retrospectively
      reviewed all patients who had had buccinator myomucosal flaps created at the
      Groote Schuur Hospital between 1999 and 2004. Patients were also recalled to
      assess flap sensation and to record reduction of mouth opening as a consequence
      of donor site scarring. RESULTS: Of the 14 patients who had had a buccinator
      myomucosal flap created, there was one flap failure. Sensation was present in 71
      per cent of flaps, and there was no trismus due to donor site scarring.
      CONCLUSIONS: The buccinator myomycosal flap is a dependable flap with good
      functional outcome and low morbidity.

PMID- 17517162
TI  - Challenges in management of chronic suppurative otitis media in a developing
      country.
AB  - BACKGROUND: In developing countries, the rate of complications from chronic
      suppurative otitis media is still high, due to factors associated with poverty.
      This study aimed to determine the prevalence of chronic suppurative otitis media
      and associated complications. PATIENTS AND METHODS: We prospectively studied all
      patients presenting with chronic suppurative otitis media to the ear, nose and
      throat unit of the Obafemi Awolowo University Teaching Hospitals Complex, Ile
      Ife, Nigeria, over a two-year period. RESULTS: One hundred and sixty new cases of
      chronic suppurative otitis media were seen. These constituted 11.1 per cent of
      all new cases and 21.5 per cent of all otological cases seen. About half (51.7
      per cent) of these patients were younger than 15 years. Most patients were from
      rural areas and had been previously managed by unlicensed, untrained
      practitioners. Complications were mostly seen in children. Intracranial
      complications were seen in 10 (6.3 per cent) cases; this was associated with a
      high mortality rate. CONCLUSION: This study found that, in Nigeria, a developing
      country, 'safe' chronic suppurative otitis media was not without serious
      problems. Provision of adequate health facilities may reduce such problems.

PMID- 17517163
TI  - Bi-lobar post-auricular skin flap for reconstruction of the earlobe.
AB  - INTRODUCTION: Ear lobule deformities can occur as a result of trauma. Surgical
      reconstruction can be challenging. There does not appear to be a consensus on the
      best form of repair. We report the case of a 27-year-old woman who suffered
      traumatic loss of the ear lobule during childhood. A novel technique is described
      using a posterior based bi-lobar flap to completely reconstruct the ear lobule in
      two stages. DISCUSSION: This form of repair has the advantage of a well-hidden
      scar, with the donor site providing skin of similar thickness and pigmentation.

PMID- 17517164
TI  - Magnetic resonance identification of an accessory submandibular duct and gland:
      an unusual variant.
AB  - We report a case of an accessory submandibular gland and duct which is extremely
      rare. MATERIAL AND METHODS: A 20-year-old male presented with complaints of
      painful swelling in the right submandibular region. As a part of the radiological
      investigation, a radiograph occlusal view was taken digital sialography, magnetic
      resonance imaging and magnetic resonance sialography were performed. RESULTS:
      Digital sialography revealed a small calculus distal to the punctum with diffuse
      dilatation of the main duct and intraglandular branches, which passed out
      spontaneously prior to magnetic resonance examination. The presence of an
      accessory submandibular duct was well delineated on both digital as well as
      magnetic resonance sialography. CONCLUSIONS: Magnetic resonance sialography is
      helpful in delineating the anatomy of the submandibular duct non-invasively and
      without associated radiation exposure. To the best of our knowledge this is the
      first report of magnetic resonance identifying an accessory submandibular duct
      and gland.

PMID- 17517165
TI  - Acute disseminated encephalomyelitis after mastoid surgery in a child.
AB  - We present a case of acute disseminated encephalomyelitis after mastoid surgery
      in an 11-year-old child. The aim of this paper is to increase awareness about a
      previously unreported and an unusual neurological complication of cholesteatoma
      and mastoid surgery.

PMID- 17517166
TI  - Otophyma: a case report.
AB  - OBJECTIVE: We report a rare case of otophyma. METHOD: A case report of otophyma
      and a review of the current literature concerning otophyma and the more common
      rhinophyma, are presented. RESULTS: A 46-year-old male presented with slow
      growing fleshy growths on both auricles which were excised. A diagnosis of
      otophyma was made. Although rosacea is more common, otophyma and other 'phymas'
      are thought to be the end stage of the rosacea spectrum of skin disease. However,
      unlike rhinophyma, otophyma is rarely seen and as a result there is little in the
      English language literature regarding it. Consequently, the management of
      otophyma is largely based on previous experiences with rhinophyma. CONCLUSION: To
      our knowledge this is the first case report of otophyma in the otolaryngology
      literature and only the second described in the English language literature. This
      case demonstrates the difficulties faced in diagnosing this rare condition and
      our successful management of this case.

PMID- 17517167
TI  - Non-recurrent laryngeal nerve related to thyroid surgery: report of three cases.
AB  - PURPOSE OF THE STUDY: We aimed to highlight a rare anatomical variation involving
      the recurrent laryngeal nerve, and to emphasise its implications for thyroid
      surgery. MATERIALS AND METHODS: Over a period of 13 years, 993 patients underwent
      thyroid surgery; 1557 recurrent laryngeal nerves (887 on the right side) were
      exposed. RESULTS: Three non-recurrent laryngeal nerves were found on the right
      side, associated with a retro-oesophageal subclavian artery. One case was
      suspected before surgery. DISCUSSION: Several variations in the path and branches
      of the recurrent laryngeal nerve have been reported in the literature. The
      frequency of occurrence of a non-recurrent laryngeal nerve is about 1 per cent,
      for patients undergoing thyroid surgery. Other surgically relevant anatomical
      variations of the recurrent laryngeal nerve include associations with the
      inferior thyroid artery and the presence of nerve branches. CONCLUSION: The
      recurrent laryngeal nerve must be carefully dissected and totally exposed during
      thyroid surgery in order to best preserve its function. Moreover, the thyroid
      surgeon must be aware of the existence of anatomical variations, which are not as
      rare as one may think.

PMID- 17517168
TI  - Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to
      regulate alcohol-seeking in rats.
AB  - Adenosine and glutamate have been implicated as mediators involved in the self
      administration of alcohol. In the present study we sought to determine whether
      adenosine receptors could interact with metabotropic glutamate receptors to
      regulate operant responding for alcohol and also the integration of the salience
      of alcohol-paired cues. Alcohol-preferring (iP) rats were trained to self
      administer alcohol under operant conditions. The availability of alcohol was
      paired with an olfactory cue plus a stimulus light. Rats were examined under
      fixed ratio responding and also following extinction under a cue-induced
      reinstatement paradigm. Administration of the selective adenosine A2A receptor
      antagonist, SCH 58261, reduced fixed ratio responding for alcohol in iP rats in a
      dose-related manner. Furthermore, the combination of a subthreshold dose of SCH
      58261 with a subthreshold dose of the mGlu5 receptor antagonist MTEP also reduced
      alcohol self-administration and increased the latency to the first reinforced
      response, suggesting a pre-ingestive effect. Moreover, this combination of SCH
      58261 and MTEP also prevented the conditioned reinstatement of alcohol-seeking
      elicited by the re-presentation of cues previously paired with alcohol
      availability. In contrast, combinations of the selective adenosine A1 receptor
      antagonist, DPCPX, with either SCH 58261 or MTEP had no effect on alcohol
      responding. Collectively, these data suggest a functional interaction between
      adenosine A2A and mGlu5 receptors in relation to alcohol-seeking and the
      integration of the drug-related cues.

PMID- 17517169
TI  - Obesity and time preference: the health consequences of discounting the future.
AB  - Much focus has been placed on the obesity epidemic due to its high prevalence and
      the costs it imposes on society. Using 2004 data from the Roper Center,
      complemented with 2003 data from the Behavioural Risk Factor Surveillance System,
      this study analyses the possible effect that time preference has on health in the
      United States, as measured by the body mass index. After controlling for a
      variety of covariates and correcting for potential selectivity, some evidence of
      a positive association between time preference for the present and the body mass
      index can be found, particularly for males. Research in this area has policy
      implications in terms of creating incentives for those who lack self-control
      through the use of pre-commitment devices. Measures addressing self-control
      issues may be more effective in reducing the rising obesity rates across the
      world.

PMID- 17517170
TI  - Comparison of cysteine peptidase activities in Trichobilharzia regenti and
      Schistosoma mansoni cercariae.
AB  - Cercariae of the bird schistosome Trichobilharzia regenti and of the human
      schistosome Schistosoma mansoni employ proteases to invade the skin of their
      definitive hosts. To investigate whether a similar proteolytic mechanism is used
      by both species, cercarial extracts of T. regenti and S. mansoni were
      biochemically characterized, with the primary focus on cysteine peptidases. A
      similar pattern of cysteine peptidase activities was detected by zymography of
      cercarial extracts and their chromatographic fractions from T. regenti and S.
      mansoni. The greatest peptidase activity was recorded in both species against the
      fluorogenic peptide substrate Z-Phe-Arg-AMC, commonly used to detect cathepsins B
      and L, and was markedly inhibited (> 96%) by Z-Phe-Ala-CHN2 at pH 4.5. Cysteine
      peptidases of 33 kDa and 33-34 kDa were identified in extracts of T. regenti and
      S. mansoni cercariae employing a biotinylated Clan CA cysteine peptidase-specific
      inhibitor (DCG-04). Finally, cercarial extracts from both T. regenti and S.
      mansoni were able to degrade native substrates present in skin (collagen II and
      IV, keratin) at physiological pH suggesting that cysteine peptidases are
      important in the pentration of host skin.

PMID- 17517172
TI  - Current status and future directions of surgery for lung cancer in China.

PMID- 17517171
TI  - Investigation of the relaxant effects of propofol on ovalbumin-induced asthma in
      guinea pigs.
AB  - BACKGROUND AND OBJECTIVE: Because the incidence of asthma appears to be
      increasing, the importance of proper perioperative management of individuals with
      asthma will also continue to increase. Although its mechanism of smooth muscle
      relaxation is unknown, propofol has been associated with less bronchoconstriction
      during anaesthetic induction. The aim of this study was to investigate the
      possible mechanism of these effects and the effects of propofol on the isolated
      trachea preparations from control and ovalbumin-sensitized guinea pigs. METHODS:
      Adult male guinea pigs, weighing 280-330 g, were randomly allocated to two
      experimental groups, each consisting of 10 animals. Ten guinea pigs were
      sensitized by intramuscular injections of 0.30 mL of a 5% (w/v) ovalbumin/saline
      solution into each thigh (0.6 mL total) on days 1 and 4, whereas the remaining 10
      served as controls receiving a total of 0.6 mL distilled water on days 1 and 4 as
      placebo. The isolated trachea preparations were mounted in tissue baths with
      modified Krebs-Henseleit solution and aerated with 95% oxygen and 5% carbon
      dioxide. We tested the effects of propofol (10(-7)-10(-3) M) on resting tension
      and after precontraction with carbachol and histamine on isolated trachea
      preparations from control and ovalbumin-sensitized guinea pigs. We also tested
      the effect of propofol on isolated trachea preparations precontracted with
      carbachol and histamine in the absence and presence of different inhibitors or
      antagonists. We investigated propofol responses in tracheal smooth muscle
      precontracted with CaCl2. RESULTS: Propofol (10(-7)-10(-3) M) produced a
      concentration-dependent relaxation of isolated tracheal preparations
      precontracted by carbachol (10(-6) M) and histamine (10(-6) M) in both groups.
      Preincubation with N(w)-nitro L-arginine methyl ester (3x10(-5) M), indomethacin
      (10(-5) M) or propranolol (10(-4) M) did not produce a significant alteration on
      propofol-induced relaxation responses (P>0.05), while preincubation with
      tetraethylammonium (3x10(-4) M) significantly decreased the propofol-induced
      relaxation responses in both groups (P<0.05). Propofol (10(-7)-10(-3) M) induced
      concentration-dependently relaxations in isolated trachea rings precontracted
      with CaCl2 in both the control and ovalbumin-sensitized groups. CONCLUSION:
      Propofol induced concentration-dependent relaxations in precontracted, isolated
      trachea smooth muscle of guinea pigs in both the control and ovalbumin-sensitized
      groups. These relaxations were independent of epithelial function and stimulation
      of beta adrenergic receptors. Opened Ca2+-sensitive K+ channels and inhibited L
      type Ca2+ channels can contribute to these relaxations.

PMID- 17517173
TI  - Radical correction of Budd-Chiari syndrome.
AB  - BACKGROUND: Interventional therapy is widely accepted as the first choice for the
      treatment of the Budd-Chiari syndrome, but the use of radical correctional
      therapy should not be discarded. This study describes radical correction by
      controlling bleeding from distal end of pathological segment of the inferior vena
      cava (IVC) and discusses potential surgical errors and postoperative
      complications. METHODS: Of the 216 patients in the study, 78 were treated with
      simple membranectomy, 64 with dissection of the pathological segment of the IVC
      and vascular prosthesis or pericardial patch plasty, 60 with resection of the
      pathological segment of the IVC and orthotopic graft transplantation with
      vascular prosthesis, and 14 with resection of the occlusive main hepatic vein and
      its upper IVC, hepatic venous outflow plasty and vascular prosthesis orthotopic
      graft transplantation from the hepatic venous entrance to the IVC of right atrial
      ostium. RESULTS: Except 14 cases who were discharged after hepatic vein outflow
      plasty, four cases died postoperatively, and 198 patients were discharged without
      complications. The symptoms of 15 patients were relieved partially and 2 without
      any change. There were no deaths intraoperatively. Of the 112 cases who were
      followed up for 72 months, 13 suffered from a relapse. CONCLUSIONS: Radical
      correction is a beneficial therapy in the treatment of Budd-Chiari syndrome.

PMID- 17517174
TI  - Radical surgery for Budd-Chiari syndrome through exposure of the entire inferior
      vena cava of the hepatic segment.
AB  - BACKGROUND: Several kinds of radical surgery for the treatment of Budd-Chiari
      syndrome (BCS) have been devised. We have described preliminary efforts to treat
      BCS using a novel radical resection technique to expose the entire inferior vena
      cava (IVC) of the hepatic segment. METHODS: Sixty patients with BCS were treated
      by radical resection, including 46 men and 14 women. BCS patients ranged in age
      from 11 to 62 years, with 3 months to 11 years since the BCS diagnosis. The
      lesions included membrane occlusion of the IVC in 16 patients, double membranes
      within the IVC in 2 patients, double membranes within the IVC and the hepatic
      vein (HV) in 3 patients, IVC membrane with distal thrombosis in 10 patients, long
      segment thrombosis of the IVC in 5 patients (organized thrombosis in 2 patients,
      fresh thrombosis in 3 patients), occlusion of the outlet of the HVs due to mural
      thrombosis in 2 patients, segmental occlusion of the IVC in 3 patients, membranes
      within the HV with IVC stenosis due to protrusion of HV stent in 1 patient, HV
      membranes in 11 patients, extensive occlusion of HVs in 1 patient, the whole IVC
      tumor thrombus with tumor thrombus of 2/3 right atrium resulting from a posterior
      peritoneum tumor in 1 patient, IVC leiomyosarcoma in 2 patients, IVC
      leiomyosarcoma with tumor thrombus into 1/2 right atrium in 1 patient, IVC
      thrombosis extending into right atrium in 1 patient, compression of supra-hepatic
      segment of IVC due to fiber trabs in 1 patient. RESULTS: All lesions were
      successfully resected under direct supervision. Three procedures were performed
      under extracorporeal circulation, 52 patients with catheterization of the right
      atrium, 4 patients with a cell saver, and one patient with auto-retrieval of
      blood. The retrieved blood was from 300 ml to 4000 ml. Transfusion of banked
      blood was from 400 ml to 2000 ml for 14 patients. For the other patients no
      transfusion of banked blood was required. One patient died of renal failure peri
      operatively. Newly formed IVC membrane was found for one recurrent patient whose
      IVC thrombosis was removed one year prior. Restenosis of the IVC was observed
      post-operatively without symptoms in one patient. In the other patients, no
      recurrent symptom was found during the follow-up periods. CONCLUSION: This novel
      surgery provides a clear visual field during the procedure and yields
      satisfactory short and long-term results.

PMID- 17517175
TI  - Intra-operative frozen section diagnosis of breast lesions: a retrospective
      analysis of 13,243 Chinese patients.
AB  - BACKGROUND: Although cytological methods for breast oncology have been used in
      recent decades, intra-operative frozen section has been playing a vital role in
      making therapeutic decisions. We analyzed a large series of frozen section
      diagnoses for Chinese cases of breast lesion within the last 15 years. The
      experience was expected to increase the diagnostic accuracy of cases with breast
      lesions. METHODS: The data from consecutive 13243 cases of breast lesions
      diagnosed with intra-operative frozen sections between 1988 to 2002 were compared
      with paraffin sections in a case by case manner. The causes of false negative and
      positive diagnoses as well as delayed diagnoses were analyzed. RESULTS: One
      hundred and seventeen cases (0.9%) were falsely diagnosed, with one false
      positive case and 116 false negative cases. The diagnosis of 47 cases (0.4%) was
      delayed. The proportion of several lesions had the features of the patients'
      ages. Six types (false invasion, peri-papilloma, adenoma of nipple duct, florid
      adenosis, sclerosing adenosis, and granulose cell tumor) of lesions may lead to
      false positive, and four types (morphological changes responding chemotherapy,
      well differentiated papillary carcinoma, invasive lobular carcinoma, and tubular
      carcinoma) to a false negative. Gross and microscopic findings may be
      inconsistent in two types of lesions (radial scar and florid adenosis)
      microscopic and clinical findings in three types (ganulomatous mastitis mammary,
      duct ectasia, and fat necrosis), and three types (abundant fat or sclerous
      tissues; borderline lesions and changes of post-chemotherapy) were likely wrongly
      classified. CONCLUSIONS: Intra-operative frozen section can accurately identify
      breast lesions in many instances, leading to fewer errors on account of more
      diagnostic experience and understanding of diagnostic limitations.

PMID- 17517176
TI  - Hilar cholangiocarcinoma: preoperative evaluation with a three dimensional
      volumetric interpolated breath-hold examination magnetic resonance imaging
      sequence.
AB  - BACKGROUND: Early detection and accurate staging are crucial for planning
      treatment and improving survival rate of hilar cholangiocarcinomas. This study
      investigated the diagnostic value of a three dimensional, spoiled gradient echo,
      T1-weighted magnetic resonance (MR) imaging sequence (3D volumetric interpolated
      breath-hold examination, 3D-VIBE) in the preoperative evaluation of hilar
      cholangiocarcinoma. METHODS: Thirty-one patients with surgically and
      histologically confirmed hilar cholangiocarcinomas underwent preoperative MR
      imaging examination. Unenhanced two-dimensional T1- and T2-weighted images, 2D MR
      cholangiopancreatographs (MRCP), gadolinium enhanced 3D-VIBE images in the early
      arterial, late arterial and portal venous phases followed by 2D T1-weighted
      images in the equilibrium phase were acquired. Images from 3D-VIBE, 2D T1
      weighted enhanced sequences and 2D MRCP were interpreted by two abdominal
      radiologists through consensus reading in blind manner, focussing on the
      assessment of the morphological type, the longitudinal extent of tumor
      infiltration in the bile ducts and the involvement of neighbouring blood vessels.
      The accuracy of 3D-VIBE and 2D T1-weighted enhanced sequences in assessing the
      tumor resectability was compared. RESULTS: All the 31 tumors were directly
      displayed and accurately classified on 3D-VIBE images whereas 8 periductal
      infiltrating tumors (8/31, 25.8%) were not depicted on 2D T1-weighted enhanced
      images. Using the Bismuth Corlette classification, 3D-VIBE was closer to MRCP in
      delineating the intraductal extent of tumor infiltration than 2D T1-weighted
      enhanced (28/31, 90.3%; 10/31, 32.3%; chi2 = 22.0, P < 0.05). Involvement of the
      hepatic artery, the portal venous trunk and their branches was shown more
      frequently on 3D VIBE than 2D T1-weighted enhanced images. The positive
      predictive value and accuracy of 3D-VIBE (84.2%; 90.3%) for assessing tumor
      resectability were higher than those of 2D T1-weighted enhanced images (64.0%;
      71.0%, all P < 0.05). CONCLUSION: Gadolinium enhanced 3D-VIBE is better than 2D
      T1-weighted enhanced sequence in the preoperative assessment of the
      morphologicalal type, the intraductal infiltrating extent and the tumor
      resectability of hilar cholangiocarcinomas.

PMID- 17517177
TI  - Evaluation of NR2B peptide as subunit vaccines against experimental neuropathic
      pain.
AB  - BACKGROUND: NR2B containing N-methyl-D-aspartate (NMDA) receptor plays an
      important role in the facilitation and maintenance of neuropathic pain. The
      discrete distribution of NR2B subunit in the central nervous system (CNS) may
      support reduced side effects of agents that act selectively at this site.
      Therefore, we investigated the hypothesis that a humoral autoimmune response
      targeting the NR2B subunit of NMDA receptor relieves pain like behaviours
      produced by peripheral injury. METHODS: Rats were immunized subcutaneously with
      NR2B-Keyhole Limpet Hemocyanin (NR2B-KLH) three times at two-week intervals. NR2B
      specific IgG titres in sera and cerebrospinal fluid were determined by indirect
      ELISA. Seven days after the third immunization, 2 of the 3 terminal branches of
      the sciatic nerve (tibial and common peroneal nerves) were tightly ligated.
      Behavioural testing was carried out on every other day after surgery, until 7
      days after surgery. The lumbar spinal cord (L4-6) was removed on day 7 after
      ligation. The expression of NR2B protein in the lumbar spinal cord was determined
      using Western blotting. RESULTS: After the second vaccination, NR2B specific IgG
      in sera was detected to be > 0.5 microg/ml in six of nine rats. After the third
      vaccination, all the immunized rats had > 2.2 microg/ml. Titres of NR2B specific
      IgG in sera peaked 42 days post initial immunization and persisted for over 70
      days. No NR2B specific IgG was detected in sera from PBS or KLH group. The
      behavioural thresholds in NR2B group were significantly higher than those in PBS
      and KLH groups on day 7 after ligation. NR2B specific IgG in CSF in NR2B group
      could not be detected on day 1 before spinal dissection; but could be detected on
      day 7 after surgery. The expression of NR2B protein in group NR2B was
      significantly lower than in PBS and KLH groups on day 7 after surgery.
      CONCLUSION: The NR2B peptide could be used as a vaccine against neuropathic pain,
      which could be associated with reduction of NR2B protein in the lumbar spinal
      cord.

PMID- 17517178
TI  - Diagnosis and treatment of pulmonary mucosa-associated lymphoid tissue lymphoma.
AB  - BACKGROUND: Primary non-Hodgkin's lymphoma in lung is very rare, and the most
      common among them is mucosa-associated lymphoid tissue lymphoma (MALToma), whose
      clinical features and laboratory characteristics are poorly defined, making
      diagnosis difficult. The purpose of this study was to study the diagnosis and
      treatment of pulmonary MALToma. METHODS: The clinical data of 12 patients treated
      for MALToma between August 1992 and December 2005 were analyzed. RESULTS: No
      specific symptoms or signs, or results of bronchoscopy, ultrasonagraphy or bone
      marrow examination could be found in the 12 patients. Only radiography was useful
      in diagnosis, though the final diagnosis of all the patients was based on
      histology and immunohistochemistry. Two patients also had gastric MALToma.
      Operations were performed on 6 patients, including 5 radical operations and 1
      partial resection: 4 patients also received adjuvant chemotherapy. One patient
      experienced recurrence 152 months after the operation, while the other 5 patients
      have survived disease-free. Four patients were treated with chemotherapy alone,
      two of whom experienced complete remission and the others partial remission. The
      final 2 patients received no treatment and had survived for 7 and 27 months
      respectively. All the patients were still alive at the most recent follow-up, 7
      to 160 months (mean 71.3 months). CONCLUSIONS: Except radiography, no specific
      clinical manifestations could be identified for pulmonary MALToma. The final
      diagnosis should be based on histology and immunohistochemistry. Several
      treatment methods can be used to achieve good outcomes.

PMID- 17517179
TI  - Generation of cytotoxic T lymphocytes specific for B-cell acute lymphoblastic
      leukemia family-shared peptides derived from immunoglobulin heavy chain framework
      region.
AB  - BACKGROUND: Immunoglobulin heavy chain variable region (IgHV) is a well
      characterized tumor antigen for B-cell malignancies. It can function as a target
      for T cell-mediated immune response. Clinical trials of IgHV protein vaccines
      against lymphoma have demonstrated induction of tumor-specific cytotoxic T
      lymphocyte (CTL) responses. However, complementary determining regions-based
      individual vaccines have disadvantages for wide clinical application. Although a
      recent study demonstrated that immunogenic peptides are derived from framework
      regions (FR) shared among patients with B-cell lymphoma, how to choose the
      appropriate peptides for each patient is still unsolved. The aim of this study
      was to investigate whether immunoglobulin heavy chain FR-derived peptides shared
      in each IgHV family are potential CTL epitopes presented by B-cell acute
      lymphoblastic leukemia (B-ALL). Such CTL epitopes might be beneficial to shifting
      vaccination strategies against B-ALL from individual specificity to family
      specificity. METHODS: Seven IgHV gene families were amplified respectively by PCR
      and sequenced directly from 71 childhood B-ALL cases. Bioinformatics was applied
      in analyzing characteristics of sequences available and predicting HLA-A*0201
      restricted CTL epitopes for each IgHV family. An antigen-specific T cell
      expansion system was used to generate peptide-specific CTLs. The cytotoxicity of
      CTLs against B-ALL cells was assessed in the lactate dehydrogenase release assay.
      RESULTS: Complete IgHV rearrangements were identified in all of the 71 B-ALL
      cases. All of 40 sequences available showed > or = 98% homology with the nearest
      germline IgHV genes, indicating IgHV genes in B-ALL of germline nature. Twelve
      nonapeptides of high HLA-A*0201-binding scores were obtained from 26 productive
      IgHV protein sequences. Ten (83%) of the peptides were located in FR1 and FR3
      shared among the corresponding IgHV family. CTLs specific for the peptide
      QLVQSGAEV located in FR1 (3 - 11) shared among the IgHV1 family could be
      successfully generated from peripheral blood mononuclear cells of two HLA-A*0201
      + healthy donors in vitro and were capable of killing HLA-matched B-ALL cell
      clones belonging to the IgHV1 family. CONCLUSION: Anti-B-ALL CTLs against
      immunoglobulin heavy chain FR-derived peptides have family-specific cytotoxicity.

PMID- 17517180
TI  - Mid-term effects of lung volume reduction surgery on pulmonary function in
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Now lung volume reduction surgery (LVRS) has become one of the most
      effective methods for the management of some cases of severe chronic obstructive
      pulmonary disease (COPD). We evaluated the mid-term effects of LVRS on pulmonary
      function in patients with severe COPD. METHODS: Ten male patients with severe
      COPD aged 38 - 70 years underwent LVRS and their pulmonary function was assessed
      before, 3 months and 3 years after surgery. The spirometric and gas exchange
      parameters included residual volume, total lung capacity, inspiratory capacity,
      forced vital capacity, forced expiratory volume in one second, diffusion capacity
      for CO, and arterial blood gas. A 6-minute walk distance (6MWD) test was
      performed. RESULTS: As to preoperative assessment, most spirometric parameters
      and 6MWD were significantly improved after 3 months and slightly 3 years after
      LVRS. Gas exchange parameters were significantly improved 3 months after surgery,
      but returned to the preoperative levels after 3 years. CONCLUSIONS: LVRS may
      significantly improve pulmonary function in patients with severe COPD indicating
      for LVRS. Mid-term pulmonary function 3 years after surgery can be decreased to
      the level at 3 months after surgery. Three years after LVRS, lung volume and
      pulmonary ventilation function can be significantly improved, but the improvement
      in gas exchange function was not significant.

PMID- 17517181
TI  - Expression of seprase in effusions from patients with epithelial ovarian
      carcinoma.
AB  - BACKGROUND: Seprase plays an important role in malignant cell invasion and
      metastasis by degrading the extracellular matrix. However, its clinical
      significance remains largely unknown. The objective of the current study was to
      evaluate the expression of seprase in effusions from patients with epithelial
      ovarian carcinoma and its clinical values. METHODS: Immunohistochemistry was used
      to examine the expression of seprase protein in a series of 74 malignant
      peritoneal (n = 64) and pleural (n = 10) effusions from Norwegian patients with
      epithelial ovarian carcinoma. Additionally, 34 effusions were evaluated using the
      Western blotting. Nine reactive effusions, obtained from patients with benign
      lesions, served as a control group. Statistical analyses were carried out by Chi
      square test and Kaplan-Meier method. RESULTS: In the 74 malignant effusion
      specimens, 57 (77.02%) were positive for seprase, while only 2 (22.22%) of the
      control group were positively stained (P = 0.001). In the malignant effusions, 17
      (22.97%), 22 (29.73%), 22 (29.73%), 13 (17.57%) had negative, weak, moderate and
      strong seprase protein expression, respectively. The expression of seprase
      protein was predominant in cytoplasm of carcinoma cells. Increased seprase
      protein was negatively associated with the overall survival rate of the patients
      (P = 0.03). However, there was no significant correlation between protein
      expression and FIGO stage, age, histology, and histological grade. By Western
      blotting, 27 of the 34 effusions showed the presence of both 170-kD dimeric form
      and 97-KD monomeric form of seprase while only 1 of the 34 had 170-KD dimeric
      form, which was consistent with the results of immunohistochemistry (P = 0.05).
      CONCLUSIONS: Seprase may be involved in the development of ovarian cancer, and is
      a potential predictive marker for the disease.

PMID- 17517182
TI  - Effects of chronic multiple stress on learning and memory and the expression of
      Fyn, BDNF, TrkB in the hippocampus of rats.
AB  - BACKGROUND: The effect of chronic stress on cognitive functions has been one of
      the hot topics in neuroscience. But there has been much controversy over its
      mechanism. The aim of this study was to investigate the effects of chronic
      multiple stress on spatial learning and memory as well as the expression of Fyn,
      BDNF and TrkB in the hippocampus of rats. METHODS: Adult rats were randomly
      divided into control and chronic multiple stressed groups. Rats in the multiple
      stressed group were irregularly and alternatively exposed to situations of
      vertical revolution, sleep expropriation and restraint lasting for 6 weeks, 6
      hours per day with night illumination for 6 weeks. Before and after the period of
      chronic multiple stresses, the performance of spatial learning and memory of all
      rats was measured using the Morris Water Maze (MWM). The expression of Fyn, BDNF
      and TrkB proteins in the hippocampus was assayed by Western blotting and
      immunohistochemical methods. The levels of Fyn and TrkB mRNAs in the hippocampus
      of rats were detected by RT-PCR technique. RESULTS: The escape latency in the
      control group and the stressed group were 15.63 and 8.27 seconds respectively.
      The performance of spatial learning and memory of rats was increased in chronic
      multiple stressed group (P < 0.05). The levels of Fyn, BDNF and TrkB proteins in
      the stressed group were higher than those of the control group (P < 0.05). The
      results of immunoreactivity showed that Fyn was present in the CA3 region of the
      hippocampus and BDNF positive particles were distributed in the nuclei of CA1 and
      CA3 pyramidal cells as well as DG granular cells. Quantitative analysis indicated
      that level of Fyn mRNA was also upregulated in the hippocampus of the stressed
      group (P < 0.05). CONCLUSIONS: Chronic multiple stress can enhance spatial
      learning and memory function of rats. The expression of Fyn, BDNF and TrkB
      proteins and the level of Fyn mRNA are increased in the stessed rat hippocampus.
      These suggest that Fyn and BDNF/TrkB signal transduction pathways may participate
      in the process of the enhanced learning and memory during chronic multiple
      stress.

PMID- 17517183
TI  - Minimally invasive approaches for histological diagnosis of anterior mediastinal
      masses.
AB  - BACKGROUND: Anterior mediastinal masses include a wide variety of diseases from
      benign lesions to extremely malignant tumors. Management strategies are highly
      diverse and depend strongly on the histological diagnosis as well as the extent
      of the disease. We reported a prospective study comparing the usefulness of core
      needle biopsy and mini-mediastinotomy under local anesthesia for histological
      diagnosis in anterior mediastinal masses. METHODS: A total of 40 patients with
      masses of unknown histology and located either at or near the anterior
      mediastinum received biopsy prior to treatment. The diagnostic methods were core
      needle biopsy in 28 patients and biopsy through mini-mediastinotomy under local
      anesthesia in 15 patients (including 3 patients for whom core needle biopsy
      failed to yield a definite diagnosis). RESULTS: Histological diagnosis was
      achieved in 18 of the 28 patients receiving core needle biopsy. Of them, all 4
      patients with pleural fibromas and 9 of the 12 patients (75%) with pulmonary mass
      were diagnosed definitively. In the remaining 12 patients with mediastinal mass,
      histological diagnosis was achieved in only 5 patients (41.7%). In contrast,
      biopsy through a mini-mediastinotomy failed in only 3 patients. In the remaining
      12 patients with huge mediastinal masses, who underwent mini-mediastinotomy, a
      definitive histological diagnosis was reached by pathological and/or
      immunohistochemical study (diagnostic yield 85.7% in 12 of 14 cases of
      mediastinal mass, P = 0.038 vs core needle biopsy). For the 9 patients with
      thymic epithelial tumors, the diagnostic yield was 40% (2 in 5 cases) for core
      needle biopsy and 83.3% (5 in 6 cases) for mini-mediastinotomy. There was no
      morbidity in patients receiving mini-mediastinotomy. In the 30 patients with
      biopsy-proven histological diagnosis, the results contributed to therapeutic
      decision making in 25 cases (83.3%). CONCLUSIONS: Core needle biopsy is effective
      in the diagnosis of pulmonary and pleural diseases. Yet its diagnostic yield in
      mediastinal mass is rather low. Superior to core needle biopsy, biopsy through a
      mini-mediastinotomy under local anesthesia is highly effective in the
      histological diagnosis of anterior mediastinal mass, and has a satisfactory
      diagnostic yield. The method is safe, minimally invasive, cost-effective, and
      useful in therapeutic decision making for anterior mediastinal masses.

PMID- 17517184
TI  - Effect of dopamine and metaraminol on the renal function of patients with septic
      shock.
AB  - BACKGROUND: Vasoactive drugs are often necessary for reversing hypotension in
      patients with severe infection. The standard for evaluating effects of vasoactive
      drugs should not only be based on the increase of arterial blood pressure, but
      also on the blood flow perfusion of internal organs. The effects of dopamine and
      metaraminol on the renal function of the patients with septic shock were
      investigated retrospectively in this study. METHODS: Ninety-eight patients with
      septic shock were divided into three groups according to the highest infusing
      rate of metaraminol, with the lightest infusing rate of (0.1 - 0.5, 0.6 - 1.0, >
      1.0) microgxkg(-1)xmin(-1) in group A, B and C respectively. Urine output, mean
      arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen
      (BUN), creatinine (CRE), urine albumin (U-ALB), urine beta(2)-microglubulin
      (Ubeta(2)-MG) and Apache III scores were recorded. RESULTS: Before antishock
      therapy, hypotension, tachycardia and oliguria occurred to all the 98 patients
      with septic shock and CRE, BUN, U-ALB, Ubeta(2)-MG and Apache III scoring were
      abnormal in most cases. With the antishock therapy, MAP, HR, urine output, BUN
      and CRE in all patients returned gradually to normal (P < 0.05 or < 0.01 compared
      to those before antishock therapy). U-ALB, Ubeta(2)-MG output and Apache III
      scoring also reverted but remained abnormal (P < 0.01 compared to those before
      antishock therapy). No statistically significant differences in the changes of
      these indices with the time existed among the three groups (P > 0.05).
      CONCLUSION: Dopamine and metaraminol when applied to the patients with septic
      shock could effectively maintain the circulatory stability and promote
      restoration of renal function.

PMID- 17517185
TI  - Assessment of personal noise exposure of overhead-traveling crane drivers in
      steel-rolling mills.
AB  - BACKGROUND: Noise is widespread occupational hazard in iron and steel industry.
      Overhead-traveling cranes are widely used in this industry, but few studies
      characterized the overhead-traveling crane drivers' noise exposure level so far.
      In this study, we assessed and characterized personal noise exposure levels of
      overhead-traveling crane drivers in two steel-rolling mills. METHODS: One hundred
      and twenty-four overhead-traveling crane drivers, 76 in the cold steel-rolling
      mill and 48 in the hot steel-rolling mill, were enrolled in the study. Personal
      noise dosimeters (AIHUA Instruments Model AWA5610e, Hangzhou, China) were used to
      collect full-shift noise exposure data from all the participants. Crane drivers
      carried dosimeters with microphones placed near their collars during the work
      shifts. Work logs had been taken by the drivers simultaneously. Personal noise
      exposure data were divided into segments based on lines in which they worked. All
      statistical analyses were done using SPSS 13.0. RESULTS: The average personal
      noise exposure (L(Aeq.8h)) of overhead-traveling crane drivers in the hot steel
      rolling mills ((85.03 +/- 2.25) dB (A)) was higher than that in the cold one
      ((83.05 +/- 2.93) dB (A), P < 0.001). There were 17 overhead traveling cranes in
      the hot steel-rolling mill and 24 cranes in the cold one, of which carrying
      capacities varied from 15 tons to 100 tons. The average noise exposure level
      based on different lines in the hot and cold steel-rolling mills were (85.2 +/-
      2.61) dB (A) and (83.3 +/- 3.10) dB (A) respectively (P = 0.001), which were
      similar to the average personal noise exposure in both mills. The noise exposure
      levels were different among different lines (P = 0.021). CONCLUSION: Noise
      exposure levels, depending upon background noise levels and the noise levels on
      the ground, are inconstant. As the noise exposure levels are above the 85 dB (A)
      criteria, these drivers should be involved in the Hearing Conservation Program to
      protect their hearing.

PMID- 17517186
TI  - Regulating effects of arsenic trioxide on cell death pathways and inflammatory
      reactions of pancreatic acinar cells in rats.
AB  - BACKGROUND: It is accepted that inflammatory cytokines play a key role in the
      development of acute pancreatitis, so blocking the initiation of inflammatory
      reactions may alleviate pathological changes of acute pancreatitis. We studied
      the regulatory effect of arsenic trioxide (As(2)O(3)) on apoptosis and oncosis of
      pancreatic acinar cells in vitro and in vivo and its therapeutic effect on acute
      pancreatitis. METHODS: Pancreatic acinar cells were isolated by collagenase
      digestion method. Apoptosis and oncosis of isolated pancreatic acinar cells were
      detected with Hoechst 33258 + PI or Annexin V + PI double fluorescent staining.
      Amylase and lactate dehydrogenase release were measured. Acute pancreatitis was
      induced in Wistar rats by intraperitoneal injections of caerulein, and apoptosis
      was detected with terminal dUTP nick-end labeling method. Tumor necorsis factor
      alpha (TNF-alpha) mRNA, myeloperoxidase, nuclear factor-kappaB and histological
      grading of pancreatic damage were measured. RESULTS: There was an increased
      apoptosis but a decreased oncosis of pancreatic acinar cell after the treatment
      with As(2)O(3). The levels of lactate dehydrogenase and amylase release were
      markedly decreased in As(2)O(3) treated group. Myeloperoxidase content, TNF-alpha
      mRNA level, nuclear factor-kappaB activation and pathological score in As(2)O(3)
      treated group were significantly lower than in the untreated group. CONCLUSIONS:
      As(2)O(3) can induce apoptosis and reduce oncosis of pancreatic acinar cell, thus
      resulting in reduced release of endocellular enzyme of acinar cells, reduced
      inflammatory cell infiltration and decreased the production of inflammatory
      cytokines, so that the outcome of alleviated pathological changes was finally
      achieved.

PMID- 17517187
TI  - Construction of tissue-engineered heart valves by using decellularized scaffolds
      and endothelial progenitor cells.
AB  - BACKGROUND: Tissue-engineered heart valves have the potential to overcome the
      limitations of present heart valve replacements. This study was designed to
      develop a tissue engineering heart valve by using human umbilical cord blood
      derived endothelial progenitor cells (EPCs) and decellularized valve scaffolds.
      METHODS: Decellularized valve scaffolds were prepared from fresh porcine heart
      valves. EPCs were isolated from fresh human umbilical cord blood by density
      gradient centrifugation, cultured for 3 weeks in EGM-2-MV medium, by which time
      the resultant cell population became endothelial in nature, as assessed by
      immunofluorescent staining. EPC-derived endothelial cells were seeded onto the
      decellularized scaffold at 3 x 10(6) cells/cm(2) and cultured under static
      conditions for 7 days. Proliferation of the seeded cells on the scaffolds was
      detected using the MTT assay. Tissue-engineered heart valves were analyzed by HE
      staining, immunofluorescent staining and scanning electron microscopy. The anti
      thrombogenic function of the endothelium on the engineered heart valves was
      evaluated by platelet adhesion experiments and reverse transcription-polymerase
      chain reaction (RT-PCR) analysis for the expression of endothelial nitric oxide
      synthase (eNOS) and tissue-type plasminogen activator (t-PA). RESULTS: EPC
      derived endothelial cells showed a histolytic cobblestone morphology, expressed
      specific markers of the endothelial cell lineage including von Willebrand factor
      (vWF) and CD31, bound a human endothelial cell-specific lectin, Ulex Europaeus
      agglutinin-1 (UEA-1), and took up Dil-labeled low density lipoprotein (Dil-Ac
      LDL). After seeding on the decellularized scaffold, the cells showed excellent
      metabolic activity and proliferation. The cells formed confluent endothelial
      monolayers atop the decellularized matrix, as assessed by HE staining and
      immunostaining for vWF and CD31. Scanning electron microscopy demonstrated the
      occurrence of tight junctions between cells forming the confluent monolayer.
      Platelets adhesion experiments suggested that the neo-endothelium was non
      thrombogenic. The expression levels of eNOS and t-PA genes in the neo-endothelium
      were quite similar to those in human umbilical vein endothelial cells.
      CONCLUSIONS: EPCs isolated from the human umbilical cord blood can differentiate
      into endothelial cells in vitro and form a functional endothelium atop
      decellularized heart valve scaffolds. Thus, EPCs may be a promising cell source
      for constructing tissue-engineered heart valves.

PMID- 17517188
TI  - Establishment of hepatocellular carcinoma multidrug resistant monoclone cell line
      HepG2/mdr1.
AB  - BACKGROUND: The multidrug resistance (MDR) associated with the expression of the
      mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of
      hepatocellular carcinoma cell (HCC) patients treated with chemotherapy. Our study
      was to establish a stable HCC MDR cell line where a de novo acquisition of
      multidrug resistance specifically related to overexpression of a transgenic mdr1.
      METHODS: The 4.5-kb mdr1 cDNA obtained from the plasmid pHaMDR1-1 was cloned into
      the PCI-neo mammalian expression vector, later was transferred by liposome to
      human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting
      G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and
      the P-glycoprotein (Pgp) in these HepG2 cells were detected by PCR, RT-PCR and
      flow cytometry, respectively. The accumulation of the daunorubicin was
      determinated by flow cytometry simultaneously. The nude mice model of grafting
      tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right
      axilla. When the tumour diameter reached 5 mm, adriamycin was injected into
      peritoneal cavity. The size and growth inhibition of tumour were evaluated.
      RESULTS: The mdr1 expression vector was constructed successfully and the MDR HCC
      line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of
      mdr1 cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells.
      Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression
      in HepG2/mdr1 cells were (59.7 +/- 7.9)% and (12.28 +/- 2.09)%, respectively,
      compared with (16.9 +/- 3.2)% and (3.07 +/- 1.06)% in HepG2 cells. In the nude
      mice HCC model, the tumour genes of both groups were identified. After ADM
      therapy, the mean size of HepG2 cell tumours was significantly smaller than
      HepG2/mdr1 cell tumours. CONCLUSION: The approach using the transfer of mdr1 cDNA
      may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR
      mechanism is known. This would provide the experimental basis of MDR research.

PMID- 17517189
TI  - Soluble expression of active human beta-defensin-3 in Escherichia coli and its
      effects on the growth of host cells.
AB  - BACKGROUND: Human beta-defensin-3 (HBD(3)) is an epithelial peptide that has been
      demonstrated to have a salt-insensitive broad spectrum of potent antimicrobial
      activity. Expressing antimicrobial peptides in Escherichia coli (E. coli) is very
      difficult for it can result in death of the bacterial host cells. Our aim was to
      establish a prokaryotic system expressing soluble HBD(3) protein and demonstrate
      the antimicrobial activity of the expressed protein. We then studied whether the
      host cells would activate the suicide pathways. METHODS: We first cloned the
      complementary DNA coding for the mature chain of HBD(3), inserted it into the
      vector PGEX-KG then transformed E. coli BL21 (DE3) with the appropriate
      recombinant plasmid. After induction with 0.5 mmol/L isopropyl-1-thio-beta-D
      galactopyranoside (IPTG) the transformed E. coli produced a recombinant
      glutathione S-transferase and HBD(3) (GST-HBD(3)) fusion protein. The fusion
      protein was treated with thrombin to produce pure HBD(3) protein then the
      antimicrobial activity of HBD(3) was evaluated in a liquid microdilution assay.
      RESULTS: The fusion protein GST-HBD(3) was efficiently cleaved by thrombin and
      yielded HBD(3) that had anti-staphylococcus aureus activity with a minimal
      inhibitory concentration level of 12.5 microg/ml. The E. coli strain expressing
      the recombinant protein did not grow slower than the empty vector strain.
      CONCLUSION: Active HBD(3) in E. coli by expressing the recombinant protein GST
      HBD(3) could be produced, and suicide did not occur in the E. coli strain
      expressing the recombinant protein.

PMID- 17517190
TI  - Protective effect of O6-methylguanine-DNA-methyltransferase on mammalian cells.
AB  - BACKGROUND: O(6)-methylguanine-DNA-methyltransferase (MGMT) is a specific DNA
      revising enzyme transferring alkylated groups from DNA to its cysteine residue to
      avoid the abnormal twisting of DNA. Therefore, it is one of the drug resistant
      genes targeted in the treatment of cancer. This study explored the protective
      effect of MGMT gene transferred into mammalian cells. METHODS: Mammalian
      expression vector containing the MGMT gene cloned from human hepatocytes by RT
      PCR was constructed and transferred into K562 cells and human peripheral blood
      mononuclear cells (PBMCs) via liposome, then assayed for gene expression at RNA
      and protein levels. MTT assay was used to check the drug resistance of cells
      transfected with MGMT gene. RESULTS: MGMT gene was successfully cloned. Real-time
      PCR showed that the mRNA expression in gene transfected groups in K562 cell line
      and PBMC were 13.4 and 4.0 times that of the empty vector transfected groups
      respectively. RESULTS: of Western blotting showed distinct higher expression of
      MGMT in gene transfected group than in other two groups. The IC(50) values
      increased to 7 and 2 times that of the original values respectively in stable
      transfected K562 cells and transient transfected PBMC. CONCLUSION: The alkylating
      resistance of eukaryotic cells is enhanced after being transfected with MGMT gene
      which protein product performs the protective function, and may provide the
      reference for the protective model of peripheral blood cells in cancer
      chemotherapy.

PMID- 17517191
TI  - A retrospective serological study of severe acute respiratory syndrome cases in
      Guangdong province, China.

PMID- 17517192
TI  - Modulatory effect of auxiliary beta1 subunit on Nav1.3 voltage-gated sodium
      channel expressed in Xenopus oocyte.

PMID- 17517193
TI  - Surgical treatment of annular pancreas in adults: a report.

PMID- 17517194
TI  - Chordoid meningioma: a report of two cases.

PMID- 17517195
TI  - Epithelioid trophoblastic tumor of the uterus: a report of.

PMID- 17517196
TI  - Blue rubber bleb nevus syndrome: a report of one case associated with recurrent
      epistaxis.

PMID- 17517197
TI  - Multiple myocardial bridges affecting left anterior descending artery and right
      coronary artery with hypertrophic cardiomyopathy: a case report.

PMID- 17517198
TI  - [Asthma education].

PMID- 17517199
TI  - [Henoch-Schonlein purpura. Study of factors associated with the development and
      course of the disease].
AB  - INTRODUCTION: Henoch-Schonlein purpura (HSP) is the most common form of pediatric
      vasculitis. The objective of this study was to determine the factors associated
      with the development and course of this disease. PATIENTS AND METHODS: A case
      control study was performed. The case group included patients with HSP followed
      up at the pediatric rheumatology and nephrology units of a tertiary university
      hospital over a 2-year period. The control group included children followed-up at
      the pediatric rheumatology unit for mechanical or non-inflammatory conditions. A
      medical history including data on infectious conditions and previous medication
      was taken. A throat culture was performed and antistreptolysin 0 levels were
      quantified. The seroprevalence of different viruses was investigated.
      Subsequently, the patients were prospectively followed-up and disease
      manifestations were compared with reported epidemiological factors. RESULTS:
      Seventy patients and 58 controls were studied. A history of a recent upper
      respiratory infection (URI) and antibiotic intake were independently associated
      with development of HSP. Palpable purpura was present in 100 % of the patients.
      Gastrointestinal manifestations were recorded in 63 %, articular in 50 %, and
      renal in 18.6 %. Arthralgias were more frequent in girls and purpura duration was
      longer when disease onset occurred in spring or summer. Other factors studied
      were not associated with disease development or with a worse clinical course.
      CONCLUSIONS: Factors associated with the development of HSP were a history of URI
      and antibiotic administration. Other epidemiological factors studied were not
      associated with either the development or the course of the disease.

PMID- 17517200
TI  - [Prenatal diagnosis of hydronephrosis: utility of diuretic renography].
AB  - OBJECTIVE: To investigate the value of diuretic renography in patients with
      prenatally diagnosed unilateral hydronephrosis. MATERIAL AND METHOD: We reviewed
      44 patients who underwent ultrasonography in the first week of life and 1 month
      after birth, and cystography and diuretic renography at 1 month to evaluate
      differential renal function and the diuretic washout pattern. Patients with
      vesicoureteral reflux were followed-up according to the protocol for this
      disorder. In the remaining patients, ultrasonography and/or diuretic renography
      was performed every 3-6 months. RESULTS: In 4/44 patients vesicoureteral reflux
      was detected as cause a of hydronephrosis. In the remaining 40 patients, diuretic
      renography showed a washout pattern not suggestive of obstruction in 32 (only one
      patient needed surgery due to pyohydronephrosis). An indeterminate washout
      pattern was detected in one patient (who required surgery due to worsening of the
      washout pattern). A pattern suggestive of obstruction was detected in seven
      patients, four of whom required surgery (three due to a decrease in differential
      renal function and one due to worsening of the degree of pelvic dilatation).
      CONCLUSIONS: Diuretic renography is highly useful in risk stratification and in
      the management of newborn infants with hydronephrosis since infants with washout
      patterns not suggestive of obstruction will rarely develop obstructive
      hydronephrosis and can initially be followed-up with ultrasonography alone. In
      indeterminate and obstructive patterns, however, close monitoring that includes
      diuretic renography is mandatory.

PMID- 17517201
TI  - [Inhaled corticosteroid therapy and bone metabolism in asthmatic children].
AB  - OBJECTIVE: To explore the association between inhaled corticosteroids (ICS)
      therapy and bone metabolism. PATIENTS AND METHODS: The sample was composed of 151
      children, aged between 1 and 17 years. There were 71 asthmatics treated with ICS
      for at least 6 months (group 1), 44 asthmatics treated occasionally with ICS
      during exacerbations (group 2), and 36 healthy children (group 3). Bone mineral
      density (BMD) and markers of bone formation and resorption were measured. These
      measures, as well as other related factors, were compared among groups.
      Regression models for osteopenia and BMD were used with the group as the
      independent variable adjusted by factors with differences between groups. A two
      tailed level of p < 0.05 was used in all tests. RESULTS: No differences in BMD
      were found between groups 1 and 2 but significant differences were found between
      groups 1 and 3 (p = 0.003). No differences were found in markers of bone
      formation and resorption among the groups. No association was found between BMD
      and the type, daily dose or accumulated dose of ICS. Group 1 showed an osteopenia
      odds ratio relative to group 3 of 2.94 (95 % CI: 1.49-5.78) and an average
      reduction of BMD of 0.50 (95 % CI: 0.32-0.68) was found from group 3 to 2 and
      from group 2 to 1. In group 1, markers of bone resorption significantly increased
      in asthmatics with osteopenia compared with those without osteopenia.
      CONCLUSIONS: ICS treatment in asthmatic children seems to affect BMD. Markers of
      bone formation and resorption are unaffected. Osteopenia in these children could
      also be related to other factors that increase bone resorption.

PMID- 17517202
TI  - [Exposure to environmental tobacco smoke at home increases the need for medical
      attention for respiratory diseases in childhood].
AB  - OBJECTIVES: Children are highly vulnerable to damage from passive smoking as they
      are unable to avoid environmental tobacco, if present. Some reports have
      suggested that domestic exposure to environmental tobacco smoke can increase
      respiratory diseases in children. The aim of this study was to assess whether
      domestic passive smoking is associated with new respiratory events. METHODS: A
      descriptive, retrospective study was performed of 410 children aged less than 14
      years old. The variables studied were: a) smokers in the household, b) the number
      of cigarettes smoked per day, c) school attendance, d) the number of siblings, e)
      previous respiratory diseases among parents and siblings, f) maternal smoking in
      pregnancy, and g) the number of respiratory events recorded in the previous year.
      Univariate, bivariate and multivariate analyses were performed. RESULTS: A total
      of 50.2 % of the children cohabited with smokers at home. The mean number of
      upper respiratory tract events per child living in environments free of tobacco
      smoke was 2.53 versus 3.52 when one of the household members smoked. For
      respiratory disease as a whole, an inverse association with age was found [OR =
      0.83; (95 % CI: 0.76-0.90)] and a direct association was found with maternal
      smoking [OR = 4.56 (95 % CI; 1.84-11.34)]. With upper respiratory tract disease,
      the OR was 1.4 if the mother smoked 11-20 cigarettes/day, and was 1.9 if the
      number of cigarettes was > 20. With lower respiratory diseases, the odds ratio
      was 3.48 (95 % CI; 2.07-6.06) if the mother smoked. CONCLUSIONS: Fifty percent of
      the children studied were exposed to environmental tobacco smoke in the home.
      Younger children were at higher risk. The major risk factor for respiratory
      disease was maternal smoking and the risk increased with the number of cigarettes
      smoked. Health education is essential to protect children from tobacco smoke
      exposure.

PMID- 17517203
TI  - [The HOMA and QUICKI indexes, and insulin and C-peptide levels in healthy
      children. Cut off points to identify metabolic syndrome in healthy children].
AB  - OBJECTIVE: The aim of this study was to establish the reference values of the
      Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check
      (QUICKI) indexes, as well as those of insulin and C-peptide levels in healthy
      children and adolescents with a view to determining reference percentiles to
      detect those at cardiovascular risk. MATERIAL AND METHODS: A total of 372
      children boys and girls of different ages and at distinct pubertal stages with
      normal body mass index participated in the study. Fasting glucose, insulin and C
      peptide values were measured by chemiluminescence and the HOMA and QUICKI indexes
      were calculated. RESULTS: Fasting glucose levels were normal in all children. The
      mean values obtained for each variable were (mean (SD)): fasting glucose 87(7.75)
      mg/dL, insulin 7.74 (5.35) microU/mL, C-peptide: 1.76 (0.79) ng/mL, HOMA index
      1.72 (1.27) and QUICKI index 0.72 (0.29). All the variables progressively
      increased with age, with statistically significant differences between
      prepubertal and pubertal children. The QUICKI index showed an inverse
      relationship. In addition, significant differences were found between sexes. The
      90th percentile for all the variables was as follows: insulin 15.05 microU/mL, C
      peptide: 2.85 ng/mL, HOMA index 3.43 and QUICKI index 1.10. CONCLUSIONS: Values
      of fasting glucose, insulin, C-peptide and the HOMA index significantly increased
      with age and pubertal stage, while the QUICKI index decreased. We defined the
      90th percentile for all the parameters studied as the cut-off point to identify
      children at cardiovascular risk in our population.

PMID- 17517204
TI  - [25-Hydroxyvitamin D levels in infants. Relation with breast-feeding].
AB  - OBJECTIVE: To determine the prevalence of subclinical vitamin D deficiency among
      infants in Valencia, Spain (latitude 39.5 degrees N) and its relation with breast
      feeding. MATERIAL AND METHODS: Serum levels of calcium, phosphate, alkaline
      phosphatase, 25-hydroxyvitamin D (25-OHD) and intact parathyroid hormone (PTH)
      were measured in 60 term infants aged between 1 and 6 months (mean age: 3.9
      months), with no known bone, gastrointestinal or renal disease (33 exclusively
      breast-fed, 27 bottle-fed). Data on vitamin D supplementation and weekly direct
      sunlight exposure were also gathered. RESULTS: All infants had normal serum
      calcium, phosphate and PTH levels. Five infants (8.3 %) had 25-OHD levels < 10
      ng/ml (lower limit of normality) and all of these infants were breast-fed (15.1 %
      of the group). None of these five infants received vitamin D supplementation.
      Infants with vitamin D deficiency had slightly elevated serum alkaline
      phosphatase. Only 48 % of breast-fed infants received regular vitamin D
      supplementation. The mean serum 25-OHD concentration of breast-fed infants in
      winter (16.8 ng/ml) was significantly lower than that in bottle-fed infants in
      summer (23.6 ng/ml, p < 0.05). CONCLUSIONS: In breast-fed infants, the
      association of limited sunshine exposure and poor dietary vitamin D
      supplementation confers a high risk of subclinical vitamin D deficiency, even in
      regions with a temperate climate.

PMID- 17517205
TI  - [Therapeutic education in asthma management].
AB  - All guidelines, protocols and recommendations underline the importance of
      therapeutic education as a key element in asthma management and control.
      Considerable evidence supports the efficacy and effectiveness of this measure.
      Health personnel, as well as patients and their parents, can and should be
      educated with two main objectives: to achieve the best possible quality of life
      and to allow self control of the disease. These goals can be attained through an
      educational process that should be individually tailored, continuous,
      progressive, dynamic, and sequential. The process poses more than a few
      difficulties involving patients, health professionals, and the health systems.
      Knowledge of the various psychological factors that can be present in asthmatic
      patients, as well as the factors related to the highly prevalent phenomenon of
      non-adherence, is essential. Awareness of the factors influencing physician
      patient-family communication is also highly important to achieve the objectives
      set in therapeutic education. The educational process helps knowledge and
      abilities to be acquired and allows attitudes and beliefs to be modified.
      Patients and caregivers should be provided with an individual written action plan
      based on symptoms and/or forced expiratory volume in 1 second. Periodic follow-up
      visits are also required.

PMID- 17517206
TI  - [Respiratory function assessment in cooperative patients. Part II].
AB  - Analysis of bronchial hyperresponsiveness using bronchial provocation tests are a
      key feature in the diagnosis of asthma, as well as a valid tool for monitoring
      disease severity, clinical course, and treatment response. We review non-specific
      bronchial challenge tests, including pharmacological stimuli (methacholine,
      adenosine) and physical stimuli (exercise, hypertonic saline, cold air
      hyperventilation). Although there is some correlation among responses to the
      distinct tests, individual responses are also observed. The indication for a
      single test will depend on whether the procedure will be used for diagnostic or
      epidemiologic purposes, and on experience of its use. Frequently, complementary
      information will be obtained. Indirect airway challenges tests such as physical
      stimuli and adenosine are more specific for asthma diagnosis.

PMID- 17517207
TI  - [The Herbst triad: finger clubbing, hypoproteinemia and iron deficiency anemia
      associated with gastroesophageal reflux].
AB  - Gastroesophageal reflux with hiatal hernia has been associated with unusual
      presentations, including rumination syndrome, Sandifer syndrome (reflux
      esophagitis, iron deficiency anemia and head cocking) and the Herbst triad (iron
      deficiency anemia, hypoproteinemia and finger clubbing). We report a new case of
      this rare disease. Lack of awareness of gastroesophageal reflux as a possible
      cause of these striking symptoms could lead to complications and delayed surgery.

PMID- 17517208
TI  - [Familial hypobetalipoproteinemia secondary to a mutation in the apolipoprotein B
      gene].
AB  - Familial hypobetalipoproteinemia (FHB) is a rare genetically heterogeneous
      disorder provoking abnormally low serum levels of apoprotein (apo) B, total
      cholesterol, and low-density lipoprotein (LDL-C). Patients carrying heterozygous
      mutations in the APOB (2p24) gene are usually asymptomatic, but homozygous
      mutations cause clinical disturbances as a result of intestinal fat malabsorption
      and fat-soluble vitamin deficiency. We present an asymptomatic boy, aged 8 years
      and 7 months, with low serum levels of apo-B, total cholesterol, triglyceride,
      LDL-C and very low-density lipoprotein (VLDL-C), as well as vitamin E deficiency.
      Three asymptomatic relatives also exhibited low apo-B, total cholesterol and LDL
      C levels. The APOB (2p24) gene was fully sequenced, demonstrating a heterozygous
      mutation in exon 26 (G --> T) in all four members of this family. Familial
      genetic studies in FHB could be useful in the early detection and treatment of
      homozygous carriers.

PMID- 17517209
TI  - [Association between ataxia-telangiectasia and syringomyelia].

PMID- 17517210
TI  - [Appendicitis of the appendicular stump. A new observation].

PMID- 17517211
TI  - [Invasive disease due to Streptococcus pyogenes in a healthy, 38-day-old infant].

PMID- 17517212
TI  - [Procalcitonin, C-reactive protein and leukocyte count in very-low birth weight
      infants with late neonatal sepsis].

PMID- 17517213
TI  - [Neonatal scabies].

PMID- 17517214
TI  - [Ocular melanosis].

PMID- 17517215
TI  - [Facial vesicles].

PMID- 17517216
TI  - [Infant with symmetric acrocyanosis of both feet].

PMID- 17517226
TI  - Early prediction of poor outcome in extremely low birth weight infants by
      classification tree analysis.

PMID- 17517227
TI  - Multicenter biliary atresia outcome studies: the importance of surgical aspects.

PMID- 17517229
TI  - Transfusion thresholds for preterm infants.

PMID- 17517230
TI  - Pediatric research in the era of Clinical and Translational Science Awards.

PMID- 17517231
TI  - Closing the ventricular septal defect because you can: evidence-averse care?

PMID- 17517232
TI  - Minimal risk, yet again.

PMID- 17517233
TI  - Focus on the heart and aorta in Turner syndrome.

PMID- 17517234
TI  - Brain imaging in neonatal clinical trials: in search of a gold standard.

PMID- 17517235
TI  - What is a pediatrician and who is asking?

PMID- 17517236
TI  - A standard for assessing the risks of pediatric research: pro and con.

PMID- 17517237
TI  - Spontaneous regression of left ventricular dilation in children with restrictive
      ventricular septal defects.
AB  - OBJECTIVES: To test the hypothesis that left ventricular (LV) dilation associated
      with pressure-restrictive ventricular septal defect (VSD) often remains stable or
      regresses spontaneously, calling into question the role of interventional
      management for such defects. STUDY DESIGN: We analyzed 96 serial echocardiograms
      from 33 unoperated patients with a moderate-to-large VSD with LV dilation (LV end
      diastolic dimension [LVED] z score >2.0) at enrollment who were followed for more
      than 2 years. Records of 125 surgical patients also were reviewed. Patients were
      evaluated for evidence of persistent or progressive LV dilation; signs or
      symptoms of congestive heart failure (CHF), failure to thrive (FTT), or pulmonary
      hypertension (PAH); as well as acquired ventricular outflow obstruction or aortic
      regurgitation. LVED z scores at enrollment versus latest follow-up were compared
      using paired t tests. A random-effects model with random intercept and slope was
      fitted to account for repeated observations for each patient. RESULTS: Mean age
      at enrollment was 4.6 +/- 3.2 years, and mean follow-up was 7.8 +/- 4 years
      (range, 2.8 to 22 years), during which mean LVED z score decreased from 3.0 +/-
      0.6 to 1.2 +/- 1.3 (P < .01). LVED z score decreased in 29 of the 33 patients,
      and decreased to <2 in 26 of these 29 (79%). CONCLUSIONS: Most patients with
      pressure-restrictive VSD with moderate-to-severe LV dilation without CHF, FTT, or
      PAH will experience spontaneous resolution of LV dilation and can avoid cardiac
      surgery or catheter-based intervention.

PMID- 17517238
TI  - Growth hormone treatment and left ventricular dimensions in Turner syndrome.
AB  - OBJECTIVE: To determine whether cardiac dimensions were different in girls with
      Turner syndrome (TS) who received growth hormone (GH) compared with those who did
      not receive GH. STUDY DESIGN: This retrospective, cross-sectional study analyzed
      echocardiograms in 86 females with TS divided into GH-treated (n = 67) and
      untreated (n = 19) groups. The subjects all participated in the National
      Institutes of Health protocol between 2001 and 2006. RESULTS: The average age was
      16.2 years (range, 10 to 25 years), and average duration of GH treatment was 4.4
      years (range, 1 to 14 years). The GH-treated group was taller by approximately 7
      cm (P = .004), but cardiac dimensions normalized to body surface area (BSA),
      including septal and posterior wall thickness and left ventricular (LV) mass and
      internal diameters, did not differ significantly between the 2 groups. The
      fractional shortening index was similar in the 2 groups. Multiple regression
      analyses indicated that BSA, but not duration of GH treatment, predicted LV
      dimensions in girls with TS. CONCLUSIONS: GH treatment of girls with TS increases
      stature but does not disproportionately affect cardiac dimensions.

PMID- 17517241
TI  - Changes in myocardial function and hemodynamics after ligation of the ductus
      arteriosus in preterm infants.
AB  - OBJECTIVE: To characterize the changes in systemic hemodynamics and systolic,
      diastolic, and global myocardial performance after patent ductus arteriosus (PDA)
      ligation in very-low-birth-weight infants. STUDY DESIGN: Echocardiograms were
      performed on 23 neonates (mean gestational age, 26.2 +/- 2.2 weeks) at 2.3 +/-
      2.0 hours before PDA ligation (n = 23) and at 2.0 +/- 1.4 hours (n = 23) and 23.5
      +/- 2.5 hours after (n = 11) PDA ligation. RESULTS: Mean blood pressure, heart
      rate, load-independent contractility, shortening fraction, left ventricular (LV)
      afterload, and diastolic function did not change. Preload (early and atrial
      mitral inflow velocities) decreased immediately after ligation but remained
      unchanged thereafter. LV output decreased and systemic vascular resistance
      increased after surgery. The LV myocardial performance index (MPI), a measure of
      global myocardial performance, deteriorated acutely after ligation but improved
      by 23.5 hours after surgery. Changes in LV MPI were most closely correlated with
      changes in LV output. CONCLUSIONS: After PDA ligation, LV output and MPI
      decrease, due primarily to a decrease in LV preload, although LV contractility
      and diastolic function do not change. However, the changes in LV MPI after
      ligation also reflect an acute deterioration followed by an improvement in global
      cardiac function, because LV loading conditions remained unchanged after surgery
      and thus cannot explain the improvement in MPI by 24 hours after ligation.

PMID- 17517240
TI  - Interobserver reliability and accuracy of cranial ultrasound scanning
      interpretation in premature infants.
AB  - OBJECTIVE: To assess interobserver reliability between 2 central readers of
      cranial ultrasound scanning (CUS) and accuracy of local, compared with central,
      interpretations. STUDY DESIGN: The study was a retrospective analysis of CUS data
      from the National Institute of Child Health and Human Development (NICHD) trial
      of inhaled nitric oxide for premature infants. Interobserver reliability of 2
      central readers was assessed with kappa or weighted kappa. Accuracy of local,
      compared with central, interpretations was assessed by using sensitivity and
      specificity. RESULTS: CUS from 326 infants had both central reader and local
      interpretations. Central reader agreement for grade 3/4 intraventricular
      hemorrhage (IVH), grade 3/4 IVH or periventricular leukomalacia (PVL), grade of
      IVH, and degree of ventriculomegaly was very good (kappa = 0.84, 0.81, 0.79, and
      0.75, respectively). Agreement was poor for lower grade IVH and for PVL alone.
      Local interpretations were highly accurate for grade 3/4 IVH or PVL (sensitivity,
      87%-90%; specificity, 92%-93%), but sensitivity was poor-to-fair for grade 1/2
      IVH (48%-68%) and PVL (20%-44%). CONCLUSIONS: Our findings demonstrate
      reliability and accuracy of highly unfavorable CUS findings, but suggest caution
      when interpreting mild to moderate IVH or white matter injury.

PMID- 17517243
TI  - Are babies born to short, primiparous, or thin mothers "normally" or "abnormally"
      small?
AB  - OBJECTIVES: To examine whether the smaller size of infants born to primiparous,
      short, or thin mothers is associated with increased risks of perinatal mortality.
      STUDY DESIGN: We compared gestational age-specific patterns of "revealed" small
      for-gestational-age (SGA) birth (number of SGA births expressed as a proportion
      of fetuses remaining in utero at each gestational age) with the patterns for
      perinatal mortality among singleton late fetal deaths and live births (n =
      791,523) to Swedish mothers in 1992 to 2001. RESULTS: Based on a single standard
      for SGA, primiparae were at substantially higher risk of revealed SGA throughout
      gestation, paralleling the pattern for perinatal mortality. However, for short
      and thin women, risks of revealed SGA were much more consistent with those for
      perinatal mortality when SGA was based on height-specific or body mass index
      specific standards, respectively, rather than on the single standard. Overweight
      and obese mothers had lower revealed SGA rates based on either standard but
      higher perinatal mortality rates. CONCLUSIONS: Slower fetal growth due to
      maternal short stature or low prepregnancy body mass index appears to be
      physiologic, whereas the slower growth of fetuses born to primiparous women is
      associated with higher risks of perinatal death.

PMID- 17517244
TI  - Sleep-disordered breathing and the metabolic syndrome in overweight and obese
      children and adolescents.
AB  - OBJECTIVE: To assess whether sleep-disordered breathing (SDB) is a risk factor of
      the metabolic syndrome (MS) in children and adolescents who are overweight and to
      examine whether the severity of SDB was independently associated with glucose
      intolerance, insulin resistance, and/or dyslipidemia. STUDY DESIGN: Consecutive
      subjects who were overweight or obese underwent polysomnography, fasting blood
      sample, and oral glucose tolerance test (for calculation of area under the curve
      [AUC]). SDB was defined as a respiratory disturbance index > or = 2. MS was
      present when > or = 3 of these factors were present: waist circumference > or =
      90th percentile; fasting glucose level > or = 110 mg/dL; triglyceride level > or
      = 110 mg/dL; high-density lipoprotein cholesterol level < or = 40 mg/dL; blood
      pressure > or = 90th percentile. RESULTS: A total of 104 subjects were included
      in the study (44% boys; 58% prepubertal; mean age, 11.1 +/- 2.6 years; 69%
      obese). Mean SaO2 (odds ratio, 0.54) and SaO2nadir (odds ratio, 0.89) were
      independent, significant predictors of the presence of MS. Multiple regression
      showed significant associations between SaO2nadir and high-density lipoprotein
      cholesterol level, mean SaO2 and both AUC glucose and triglyceride levels, and
      between the percentage of total sleep time with SaO2 > or = 95% and cholesterol
      level, while controlling for adiposity and sex, puberty, or both. CONCLUSION:
      This study supports the hypothesis of an interaction between SDB and metabolic
      abnormalities, independent of estimates of body fat distribution, in children and
      adolescents who are overweight and obese.

PMID- 17517245
TI  - Homozygous null mutation of the melanocortin-4 receptor and severe early-onset
      obesity.
AB  - OBJECTIVE: To describe the clinical and biological phenotype of a child who is
      severely obese and is homozygous for a new melanocortin-4 receptor (MC4R) gene
      mutation leading to a truncated receptor. STUDY DESIGN: Direct sequencing of the
      MC4R gene was performed in a child who was severely obese and his relatives.
      Phenotypic characterization included weight evolution, anthropometric parameters,
      and endocrine and metabolic complications. Growth curves were compared with those
      of children carrying leptin receptor (LEPR) homozygous mutation, MC4R
      heterozygous mutations, and MC4R wild type allele. RESULTS: We found a homozygous
      2-base pair deletion (del 346-347AG) leading to a stop codon. This new mutation
      leads to a truncated MC4R after the second transmembrane domain in a 3-year-old
      boy with severe early-onset obesity. Segregation analysis of the mutation showed
      that the 2 parents and 2 adult relatives were heterozygous carriers for the
      mutation. Heterozygous carriers displayed an obese phenotype, but with a variable
      degree of severity. The homozygous carrier of the mutation was hyperphagic and
      showed a rapid increase in weight in the very first months of life. His weight
      evolution closely resembled that of patients who are LEPR deficient, but markedly
      differed with that of children carrying either heterozygous MC4R mutations or
      MC4R wild type allele. No other hormonal or metabolic anomaly was found in the
      child. CONCLUSIONS: This phenotype of a boy carrying a new homozygous MC4R
      mutation confirms the critical role of MC4R in the early dynamic of weight gain
      and phenotypic differences with heterozygous carriers.

PMID- 17517246
TI  - Definable somatic disorders in overweight children and adolescents.
AB  - OBJECTIVE: To analyze the frequencies and clinical presentation of definable
      somatic disorders in children who are overweight. STUDY DESIGN: We assessed
      prospectively 1405 children aged 4 to 16 years who were overweight and came to
      our specialized clinic for endocrinology and obesity with a standardized
      diagnostic procedure. In a subgroup of 223 children, we sought mutations in the
      melanocortin-4-receptor gene (MC4R). RESULTS: Endocrine or syndromal disorders
      were diagnosed in 13 children (<1%; 4 with hypothyroidism, 1 with Cushing's
      syndrome, 1 with growth hormone deficiency, 2 with pseudohypoparathyroidism, 1
      with pseudopseudohypoparathyroidism, 2 with Prader-Willi syndrome, 1 with Bardet
      Biedl syndrome, 1 with Klinefelter syndrome). A total of 85% of these children
      had short stature, in marked contrast to only 0.6% of the other children.
      Moderately elevated thyrotropin and cortisol concentrations were observed in 4%
      and 5%, respectively, of all children. Non-synonymous MC4R mutations were found
      in 6% of the children. CONCLUSIONS: In contrast to MC4R mutations, endocrine and
      clinically identifiable syndromal disorders were rare in children who were
      overweight and always associated with further symptoms. All children who are
      overweight with short stature or reduced growth velocity should be carefully
      examined for endocrine or syndromal disorders. A general screening with
      laboratory measurements cannot be recommended because thyrotropin and cortisol
      levels are frequently moderately elevated in children who are overweight, thus
      entailing further superfluous diagnostic procedures.

PMID- 17517247
TI  - The effect of CYP2D6 polymorphisms on the response to pain treatment for
      pediatric sickle cell pain crisis.
AB  - OBJECTIVES: To test the hypothesis that children taking hydroxyurea who fail
      codeine therapy have an increase in reduced-functioning cytochrome P450 2D6
      (CYP2D6) alleles. STUDY DESIGN: Children with sickle cell disease presenting to
      an emergency department with a pain crisis unresponsive to codeine were
      genotyped. The proportion of children with reduced-functioning alleles and CYP2D6
      enzyme activity scores < or = 1.5, were compared, by chi2 analysis, in children
      taking hydroxyurea and those with mild disease. RESULTS: Of the 73 children
      completing the study, 42 had reduced-functioning alleles; 82% of the 27 children
      taking hydroxyurea had reduced-functioning alleles, versus 47% of 36 those with
      mild disease (P < .05). Activity scores were decreased in 78% of the children
      taking hydroxyurea and in 44% of those with mild disease (P < .05). The odds
      ratios of children taking hydroxyurea were 4.9 (95% confidence interval [CI] =
      1.5 to 15.9) for having reduced-functioning alleles, and 4.4 (95% CI = 1.4 to
      13.4) for having a low activity score. CONCLUSIONS: Failing codeine therapy for a
      pain crisis while taking hydroxyurea is associated with an increase in reduced
      functioning CYP2D6 alleles. We recommend genetic analysis or trial of a non
      CYP2D6 analgesic for these children.

PMID- 17517248
TI  - Assessment of tetrahydrobiopterin (BH4) responsiveness in phenylketonuria.
AB  - OBJECTIVE: To determine the prevalence of and identify subjects with
      phenylketonuria (PKU; phenylalanine hydroxylase deficiency) responsive to 6R
      tetrahydrobiopterin (BH4) and to establish selection criteria for potential
      treatment with BH4. STUDY DESIGN: Blood phenylalanine levels from 557 newborns
      and children with various degrees of PKU (blood phenylalanine, 301 to 4743
      micromol/L) challenged with BH4 (20 mg/kg of body weight) were analyzed at 8 and
      24 hours after BH4 administration. The 2 modalities were compared in terms of
      phenylalanine reduction. RESULTS: The overall prevalence of BH4 responsiveness
      within patients with PKU for blood phenylalanine reductions of 20%, 30%, 40%, and
      50% was 48%, 38%, 31%, and 24%, respectively, using the 8-hour modus and 55%,
      46%, 41%, and 33%, respectively, using the 24-hour modus. Using the 30% cutoff,
      BH4 responsiveness was similar regardless of the modality in patients with mild
      hyperphenylalaninemia (79% to 83% responders), mild PKU (49% to 60% responders),
      and classical PKU (7% to 10% responders). CONCLUSIONS: BH4 responsiveness is more
      prevalent than was previously assumed, particularly in patients with mild
      hyperphenylalaninemia and mild PKU. Depending on the severity of
      hyperphenylalaninemia, selection criteria for the potential treatment with BH4
      may range from 20% to 40% blood phenylalanine reduction after 24 hours.

PMID- 17517249
TI  - Nephropathy advancing to end-stage renal disease: a novel complication of
      lysinuric protein intolerance.
AB  - OBJECTIVE: To analyze systemically the prevalence of renal involvement in a
      cohort of Finnish patients with lysinuric protein intolerance (LPI) and to
      describe the course and outcome of end-stage renal disease in 4 patients. STUDY
      DESIGN: The clinical information in a cohort of 39 Finnish patients with LPI was
      analyzed retrospectively. RESULTS: Proteinuria was observed in 74% of the
      patients and hematuria was observed in 38% of the patients during follow-up.
      Elevated blood pressure was diagnosed in 36% of the patients. Mean serum
      creatinine concentration increased in 38% of the patients, and cystatin C
      concentration increased in 59% of the patients. Four patients required dialysis,
      and severe anemia with poor response to erythropoietin and iron supplementation
      also developed in these patients. CONCLUSIONS: Our findings suggest that renal
      function of patients with LPI needs to be carefully monitored, and hypertension
      and hyperlipidemia should be treated effectively. Special attention also should
      be paid to the prevention of osteoporosis and carnitine deficiency in the
      patients with end-stage renal disease associated with LPI. The primary disease
      does not prohibit treatment by dialysis and renal transplantation.

PMID- 17517250
TI  - Self-hypnosis training for headaches in children and adolescents.
AB  - OBJECTIVE: To describe the effect of treatment with self-hypnosis for youth with
      recurrent headaches. STUDY DESIGN: A retrospective review was conducted of
      outpatient clinical records of 178 consecutive youths referred to the Behavioral
      Pediatrics Program (University of Minnesota) from 1988 to 2001 for recurrent
      headaches. All patients were taught self-hypnosis for self-regulation. Intensity,
      frequency, and duration of headaches before, during, and after treatment were
      measured. Outcomes included number and frequency of visits, types of medication,
      and nature of self-hypnosis practice. RESULTS: Data were available for 144
      patients in this patient self-selected and uncontrolled observation. Compared
      with self-reports before learning self-hypnosis, children and youths who learned
      self-hypnosis for recurrent headaches reported reduction in frequency of headache
      from an average of 4.5 per week to 1.4 per week (P < .01), reduction in intensity
      (on a self-rating scale of 0 to 12) from an average of 10.3 to 4.7, P < .01, and
      reduction in average duration from 23.6 hours to 3.0 hours, (P < .01). There were
      no adverse side effects of self-hypnosis. CONCLUSIONS: Training in self-hypnosis
      is associated with significant improvement of chronic recurrent headaches in
      children and adolescents.

PMID- 17517254
TI  - Who claims to be a pediatrician?
AB  - OBJECTIVE: The purpose of this study was to determine the proportion of
      physicians who self or otherwise declare themselves to be pediatricians but who
      have never achieved board certification. STUDY DESIGN: We compared a roster from
      the state licensure file of eight geographically diverse states containing those
      designated as pediatricians with a listing from the American Board of Pediatrics
      (ABP) of those who had ever achieved board certification. We then sent a mail
      survey to a sample of 500 physicians who appeared as pediatricians on the state
      licensure files but for whom there was no record of certification with the ABP.
      RESULTS: The proportion of unmatched pediatricians ranges from 6.9% in
      Massachusetts to 16.8% in Maryland, and averages 11% across all of the states in
      our study. The survey response rate was 64%. The majority (61%) of respondents
      described having undertaken residency training in categorical pediatrics or
      medicine-pediatrics. The remainder reported surgical residencies (31%) or were
      combined into an "other" category (8%). Eighty-five percent reported having
      completed 3 or more years of postgraduate training. Almost all (94%) completed
      training in the United States or Canada. CONCLUSIONS: There is increasing
      attention to board certification and patient safety among the media and public. A
      clearer delineation of the proportion of physicians in a given state reporting to
      be pediatricians who have not completed board certification can help inform
      parents of the odds they will encounter noncertified physicians in the hospitals
      and among the health plans in which they seek care for their children.

PMID- 17517252
TI  - Prevalence of hypertension and pre-hypertension among adolescents.
AB  - OBJECTIVE: To determine the prevalence of hypertension and pre-hypertension on
      the basis of the 2004 National High Blood Pressure Education Program Working
      Group guidelines in an adolescent school-screening population. STUDY DESIGN:
      Cross-sectional assessment of blood pressure (BP) in 6790 adolescents (11-17
      years) in Houston schools was conducted from 2003 to 2005. Initial measurements
      included height, weight, and 4 oscillometric BP readings. Repeat measurements
      were obtained on 2 subsequent occasions in students with persistently elevated
      BP. Final prevalence was adjusted for loss to follow-up and logistic regression
      used to assess risk factors. RESULTS: BP distribution at initial screen was 81.1%
      normal, 9.5% pre-hypertension, and 9.4% hypertension (8.4% Stage 1; 1% Stage 2).
      Prevalence after 3 screenings was 81.1% normal, 15.7% pre-hypertension, and 3.2%
      hypertension (2.6% Stage 1; 0.6% Stage 2). Hypertension and pre-hypertension
      increased with increasing body mass index. Sex, race, and classification as
      either at-risk for overweight or overweight were independently associated with
      pre-hypertension. Only classification as overweight was associated with
      hypertension. CONCLUSIONS: Application of new classification guidelines for
      adolescents with elevated BP reveals approximately 20% are at risk for
      hypertension. Further research determining the significance of each BP category
      and refining definitions to account for BP variability is warranted.

PMID- 17517255
TI  - Unexplained neonatal respiratory distress due to congenital surfactant
      deficiency.
AB  - Genetic abnormalities of pulmonary surfactant were identified by DNA sequence
      analysis in 14 (12 full-term, 2 preterm) of 17 newborn infants with fatal
      respiratory distress of unknown etiology. Deficiency of adenosine triphosphate
      binding cassette protein, member A3 (n = 12) was a more frequent cause of this
      phenotype than deficiency of surfactant protein B (n = 2).

PMID- 17517256
TI  - Treatment of chronic fatigue and orthostatic intolerance with propranolol.
AB  - We describe the effect of propranolol in an adolescent with chronic fatigue
      syndrome and orthostatic intolerance. Our observations suggest that the head-up
      tilt-test and beta-blocker treatment might be considered in patients with chronic
      fatigue syndrome and that enhanced sympathetic nervous activity might be part of
      the underlying pathophysiology.

PMID- 17517257
TI  - Chronic lung disease and cystic fibrosis phenotype in prolidase deficiency: a
      newly recognized association.
AB  - Six families with prolidase deficiency (PD) and chronic lung disease are
      reported, a previously unrecognized association. In one family with a classic
      cystic fibrosis (CF) phenotype, no evidence for CF Transmembrane Conductance
      Regulator (CFTR)-related mutations could be found. Chronic lung disease and CFTR
      mutation negative CF may be associated with PD.

PMID- 17517258
TI  - Virtual cardioscopy in cor triatria.

PMID- 17517260
TI  - Outdoors in Utah: a safety primer.

PMID- 17517261
TI  - Who's your hero?

PMID- 17517262
TI  - Paramedics in the emergency department.

PMID- 17517263
TI  - Response to computerized charting.

PMID- 17517264
TI  - Emergency nurses' knowledge of evidence-based ischemic stroke care: a pilot
      study.
AB  - INTRODUCTION: The purpose of this pilot study was to assess emergency nurses'
      knowledge of evidence-based ischemic stroke care. DESIGN AND METHODS: A
      descriptive, correlational design was used. Emergency nurses (N = 20) working in
      2 hospitals in the Mid-Atlantic region completed a 10-item multiple choice test
      on evidence-based ischemic stroke care. RESULTS: Test scores ranged from 30% to
      90%, with a mean of 53% (SD = 12.93) on a scale of 0 to 100%. Forty-five percent
      (N = 9) of respondents indicated that they read literature on evidence-based
      ischemic stroke care within the previous 12 months. Respondents who read
      literature on evidence-based ischemic stroke care had a significantly higher mean
      test score (P = .04) than did respondents who did not read any literature on
      evidence-based ischemic stroke care. Only 15% (N = 3) of respondents reported
      that they had participated in continuing education on evidence-based ischemic
      stroke care within the previous 12 months. In addition, there was a significant
      correlation (P = .02) between number of years worked in emergency nursing as a
      registered nurse and test scores. Nurses with more years experience in emergency
      nursing had higher test scores. DISCUSSION: Overall, emergency nurses
      demonstrated a knowledge deficit in evidence-based ischemic stroke care. The
      majority of nurses had not participated in continuing education on evidence-based
      ischemic stroke care within the previous 12 months. Nurses should be provided
      with evidence-based education on ischemic stroke care and opportunities to
      participate in continuing education.

PMID- 17517265
TI  - Managing acute head trauma in a crowded emergency department.

PMID- 17517266
TI  - The perceived value of BCEN certification.

PMID- 17517267
TI  - Walking through the ages: the impact of pedestrian injury.

PMID- 17517268
TI  - Redesign of a pediatric hospital's triage and registration area.

PMID- 17517269
TI  - ABCDs of acute stroke intervention.

PMID- 17517270
TI  - A case in successful organ donation: emergency department nurses do make a
      difference.

PMID- 17517271
TI  - A 9-year-old boy with paresthesias in his hands and weak handgrips following a
      dirt bike crash.

PMID- 17517273
TI  - Nursing clinical today: the importance of good teachers and mentors.

PMID- 17517274
TI  - Helping patients and families avoid inadvertent acetaminophen overdose.

PMID- 17517275
TI  - Caring for members of the church of Jesus Christ of Latter-Day Saints (Mormons)
      in the emergency department.

PMID- 17517276
TI  - The dark side of the job: violence in the emergency department.

PMID- 17517277
TI  - Coin lodged in the proximal esophagus.

PMID- 17517278
TI  - 2006 ENA National Scorecard on State Highway Laws: a road map for injury
      prevention.

PMID- 17517279
TI  - Emergency nursing: new countries, new challenges.

PMID- 17517281
TI  - New graduate nurse orientation in the emergency department: use of a simulation
      scenario for teaching and learning.

PMID- 17517282
TI  - Creating a safe environment for pediatric ED patients.

PMID- 17517283
TI  - A sticky situation: toxicity of clonidine and fentanyl transdermal patches in
      pediatrics.

PMID- 17517284
TI  - Peroneal nerve compression: a case review.

PMID- 17517285
TI  - Triage successes: a hospital's journey of change and growth.

PMID- 17517286
TI  - When? In the practice of surgery, timing is critical.

PMID- 17517287
TI  - Third molars and progression of periodontal pathology during pregnancy.
AB  - PURPOSE: This study was conducted to evaluate the association between third molar
      periodontal pathology at enrollment and periodontal disease progression during
      pregnancy. PATIENTS AND METHODS: The data were derived from patients in an
      institutional review board-approved prospective study known as the Oral
      Conditions and Pregnancy (OCAP) study. Demographic, health behavior, and medical
      history data were obtained from medical records. Full-mouth periodontal
      examinations of 6 periodontal probing sites for each visible tooth, including
      third molars, were conducted at less than 26 weeks of pregnancy and within 72
      hours postpartum. The primary outcome variable was periodontal progression (4 or
      more probing sites with at least a 2 mm increase in probing depth (PD), all at
      least 4 mm deep), between the enrollment and postpartum examinations. The primary
      predictor variables at enrollment were at least 1 PD >or=4 mm around the third
      molars, and the upper tertile of the number of third molar probing sites recorded
      as bleeding on probing (BOP). Bivariate analyses were performed for baseline
      characteristics. The chi2 test was used to determine statistical significance (P
      = .05). Significant variables were included in unconditional logistic
      multivariable models to derive relative risk ratios (RRs) and 95% confidence
      intervals (CIs). RESULTS: Data from enrollment and term were available for 360
      subjects with visible third molars (mean age, 27.3 years; standard deviation, 5.5
      years). At the postpartum examination, 122 subjects (34%) demonstrated
      periodontal progression. These subjects included 74 of the 176 subjects (42%) in
      whom a third molar PD >or=4 mm was detected at baseline and 48 of the 184 (26%)
      without third molar PD >or=4 mm (P = .001). Periodontal progression was found in
      40 of the 77 subjects (52%) who were in the upper tertile of the number of third
      molar probing sites exhibiting BOP at enrollment versus 82 of the 203 (29%) in
      the lower tertiles (P = .0002). In multivariable models, either third molar PD
      >or=4 mm at enrollment (RR = 1.4; 95% CI = 1.1 to 2.0) or third molar bleeding on
      probing (RR = 1.7; 95% CI = 1.3 to 2.3) was associated with periodontal disease
      progression. CONCLUSION: Third molar periodontal pathology appears to be a
      significant risk indicator for periodontal disease progression during pregnancy.

PMID- 17517288
TI  - Does early repair of lingual nerve injuries improve functional sensory recovery?
AB  - PURPOSE: This study evaluated the relationship between timing of lingual nerve
      repair and functional sensory recovery. MATERIALS AND METHODS: Using a
      retrospective cohort study design, the investigators enrolled a sample of
      subjects who had lingual nerve repair. The predictor variable was time between
      injury and repair, categorized as early (<90 days after injury) or late (>90 days
      after injury). The outcome variable was the time to functional sensory recovery
      (FSR), measured in days. Other variables were categorized as demographic,
      anatomic, and operative. Uni- and multivariate Cox proportional hazards models
      were used to evaluate the association between the timing of the repair and time
      to FSR. RESULTS: The study sample was composed of 64 subjects who had lingual
      nerve repair between January 1998 and January 2005. The mean time between injury
      and repair was 153.2 (31-1606) days; 21.9% of subjects had early repair. The mean
      age was 28.4 +/- 8.0 years, 62.5% of subjects were female; 77% of the injured
      nerves were repaired by direct suture, and 23% had surgical exploration with
      decompression/neurolysis. In bivariate analyses, early repair, method of repair,
      and neuroma were statistically or near-statistically associated with time to FSR
      (P <or= .12). In a multiple Cox proportional hazards model, early repair was
      associated with time to FSR (P = .02). Ninety-three percent of subjects in the
      early repair group achieved FSR within 1 year, compared with 62.9% in the late
      group (P = .05). CONCLUSIONS: Early repair of lingual nerve injuries results in
      FSR more frequently and earlier than late repair.

PMID- 17517290
TI  - A comparative study of 2 methods for obtaining platelet-rich plasma.
AB  - PURPOSE: Double and single centrifugation are the most commonly used techniques
      for obtaining platelet-rich plasma (PRP) in dentistry. In this study, we used and
      compared 2 methods for obtaining PRP: double centrifugation (ACE system; Surgical
      Supply and Surgical Science Systems, Brockton, MA) and single centrifugation
      (Nahita system; Nahita, Navarra, Spain). MATERIALS AND METHODS: Blood samples
      were obtained from 30 random patients. Each blood sample was treated using the
      ACE system and Nahita system methods, after which the obtained material was
      analyzed by flow cytometry for platelet counts and by transmission electron
      microscopy (TEM) for ultrastructural analysis of the PRP gel. RESULTS: Platelet
      count analysis of the PRP obtained from both methods revealed that the ACE and
      Nahita systems accomplished platelet concentrations of (336%) and (227%),
      respectively. The platelet counting results obtained from the ACE system samples
      were more dispersed than their Nahita system counterpart. The ultrastructural
      (ie, TEM) study showed considerable alterations of the platelet aggregates in the
      ACE's PRP, especially when the samples were not mixed in the final stage of the
      procedure, whereas the Nahita aggregates always had a normal physiological
      appearance. CONCLUSIONS: The ACE double-centrifugation method is able to achieve
      higher platelet concentrations than the single-centrifugation Nahita system,
      although the results obtained by ACE were more dispersed. Nevertheless, the ACE
      system provoked alterations in the PRP ultrastructure, and it was more sensitive
      to small errors during preparation.

PMID- 17517289
TI  - Recovery from postsurgical swallowing dysfunction in patients with oral cancer.
AB  - PURPOSE: The present study was focused on a comparison of postsurgical
      oropharyngeal swallowing efficiency and medical status indicators. PATIENTS AND
      METHODS: The swallowing function was assessed in 25 patients (18 males and 7
      females) with oral cancer. The swallowing function was assessed preoperatively
      and 1, 6, and 12 months and in some cases more than 24 months after surgery.
      Assessment of the swallowing function consisted of videofluoroscopic evaluation
      (oropharyngeal swallow efficiency; OPSE) and details of the method of nutrition,
      diet level, nutritional condition, and occurrence of pneumonia. RESULTS:
      Postsurgically, OPSE did not recover to the preoperative level more than 12
      months after surgery. Twenty-one patients (84%) had full oral intake and only 3
      patients (12%) showed poorer nutritional conditions compared with the presurgery
      state. Aspiration pneumonia did not occur more than 12 months after surgery.
      CONCLUSIONS: The patients in the present study showed stable medical status and
      functional swallowing at the final evaluation despite insufficient recovery of
      OPSE revealed by videofluoroscopic evaluation.

PMID- 17517291
TI  - Craniomaxillofacial injuries in the United Arab Emirates: a retrospective study.
AB  - PURPOSE: To analyze craniomaxillofacial injuries in selected hospitals in the
      United Arab Emirates (UAE). PATIENTS AND METHODS: This is a retrospective study
      of craniomaxillofacial injuries treated in 3 major hospitals in the UAE. Patient
      files were retrieved, reviewed, and analyzed. The main analysis outcome measures
      were the patients' name, age, and gender and the injuries' time, site, type,
      treatment and outcome. RESULTS: A total of 288 patients sustained 475
      craniomaxillofacial injuries; road traffic accidents caused the majority of
      injuries. The patients ranged in age from 2 to 82 years (mean, 27.3 years), and
      the male-to-female ratio was 7:1. The yearly distribution of fractures peaked
      during 2001, and the monthly distribution peaked in January. The greatest number
      (41%) of patients were UAE nationals. Most patients (70.5%) had mandibular
      fractures, and the most common site was the body. There were 139 patients (48.3%)
      with a total of 171 midface fractures (36%); the most common fracture site was
      the zygomatic complex (29.8%). The most common treatment for jaw fractures was
      plating plus intermaxillary fixation. Stable zygomatic complex fractures were
      closely reduced (elevated), and unstable ones were treated by internal fixation.
      About 25% of the cases had 1 or more postoperative complication. CONCLUSIONS:
      Craniomaxillofacial injuries in the UAE included in this study are somewhat
      similar to those reported in other countries. Differences from other countries
      are probably related to factors peculiar to the UAE, such as climate, social
      trends, and the cosmopolitan population.

PMID- 17517292
TI  - A sheep model of intracapsular condylar fracture.
AB  - PURPOSE: An animal model of a condylar head fracture similar to a type B
      intracapsular fracture in humans was created. The effect of this model on
      mandibular function and morphological changes of temporomandibular joint (TMJ)
      structure was evaluated. MATERIALS AND METHODS: Ten sheep were divided into 3
      groups, sacrificed at 1 week (2 sheep), 4 weeks (4 sheep), and 12 weeks (4 sheep)
      after surgery. The right side of the TMJ was considered the surgical group; the
      left side, the control group. The anterior and posterior attachments of the discs
      were cut, and an oblique vertical osteotomy was made from the lateral pole of the
      condyle to the medial side of the condylar neck. The condyle fragment was pushed
      together with the disc anteriorly, inferiorly, and medially. The lateral side of
      the condylar stump was sutured to the capsule to limit movement. Preoperative and
      postoperative body weight, maximum mouth opening, lateral excursions, and x-ray
      and computed tomography (CT) findings in the 3 surgical groups and the control
      group were recorded. The SPSS software program was used for all statistical
      analyses. RESULTS: There were no significant differences in weight loss and left
      lateral movement among the 3 surgical groups, but maximum mouth opening and the
      right lateral movement decreased significantly in the 4-week and 12-week surgical
      groups. X-rays demonstrated severe bone erosion and new bony outgrowth in the
      lateral side of the condylar stump and a narrowed, indistinct joint space in
      these 2 groups. Three-dimensional reconstruction of CT images showed changed
      contours of the condylar stump, condylar fragment and articular eminence in all 3
      surgical groups. CONCLUSIONS: This study demonstrates progressive changes toward
      ankylosis and pathological changes in sheep TMJ over time consistent with what
      has been found in humans.

PMID- 17517293
TI  - Biomechanical evaluation of Le Fort I maxillary fracture plating techniques.
AB  - PURPOSE: This study used a biomechanical model to examine fundamental questions
      about rigid plate fixation treatment for maxillary Le Fort I fractures.
      Specifically, we sought to elucidate the principal strain patterns generated in
      miniplates and bite force transducers secondary to all masticatory forces, as
      well as the amount of permanent deformations incurred due to these loading
      forces. MATERIALS AND METHODS: Forty polyurethane synthetic maxillary and
      mandibular replicas were used to simulate the mandible and maxilla. Ten replicas
      were controls (group A). The other 30 were divided into 3 groups (10 each),
      according to the fixation techniques of 3, 2, and 1 miniplates each side (groups
      B-D), that were osteotomized in the Le Fort I fracture line on the maxilla.
      Different forces of masseter medial pterygoid, temporalis, and lateral pterygoid
      muscles were loaded onto the replicas to simulate different functional conditions
      (anterior incisor, premolar, and molar clenching). Rosette strain gauges were
      attached at predefined points on the plates and the bite force transducer to
      compare the stability and bite force of the different fixation methods for
      maxillary Le Fort I fractures. RESULTS: Statistically significant differences
      were found for the deformation of the plates among fixation techniques. The order
      of stability for each technique was: group B greater than group C greater than
      group D. In regard to bite force, no difference was found between those found
      with group A and group B (P > .05), whereas the bite forces of groups C and D
      were less than those of group A (P < .05). CONCLUSIONS: The fixation of 3
      miniplates on each side provides sufficient stability and restores the bite force
      to the level of the intact maxilla. "The ideal fixation" with 2 miniplates on
      each side restores 90% of the bite force, and there were more deformations of the
      miniplates with the "ideal fixation" compared to those found with group B. Group
      D fixation produced the worst effects for the treatment of maxillary Le Fort I
      fractures with a weak bite force and insufficient stability.

PMID- 17517294
TI  - Primary malignant melanoma of the oral mucosa.
AB  - PURPOSE: To present our experience on the epidemiology, clinical features,
      management, and survival of patients with oral malignant melanoma. PATIENTS AND
      METHODS: Records of patients with a histologic diagnosis of primary oral mucosal
      malignant melanoma seen over a 23-year period were retrospectively reviewed.
      RESULTS: There were 6 females and 2 males, ranging in age from 18 to 60 years; 4
      cases in the maxilla, 2 in the mandible, 1 on the lower lip, and 1 on the buccal
      mucosa. Local recurrences developed in 2 patients who eventually died with
      clinical metastatic cervical nodal disease. Follow-up ranged from 6 months to 16
      years 3 months. Surgery was the only treatment available. CONCLUSION: Primary
      oral mucosal melanoma is rare, with a 3 to 1 female to male ratio and an average
      age of 41.7 years at presentation. It is most common in the maxilla and has poor
      prognosis despite apparent adequate local surgical control.

PMID- 17517295
TI  - Efficacy of xenogeneic bone grafting with guided tissue regeneration in the
      management of bone defects after surgical endodontics.
AB  - PURPOSE: The purpose of this prospective clinical trial was to monitor the
      outcomes of periradicular surgery in large periapical lesions with or without
      guided tissue regeneration (GTR) and anorganic bovine bone. MATERIALS AND
      METHODS: All teeth in the study revealed a periradicular lesion measuring at
      least 10 mm. A total of 63 teeth in 44 patients were included according to
      specific selection criteria. In the test group, after root end filling was
      completed, the defect was filled with anorganic bovine bone and was covered with
      a resorbable collagen membrane. In the control group, neither graft nor membrane
      was used. RESULTS: A total of 59 teeth in 41 patients were evaluable at 1-year
      follow-up. Of these, 24 teeth belonged to the test group and 35 to the control
      group. Overall, 46 teeth (78%) had successfully healed, 10 (16.9%) demonstrated
      uncertain healing, and 3 exhibited treatment failure. Investigators found no
      statistically significant differences in outcome between test and control groups.
      CONCLUSIONS: The present study showed that the use of GTR in association with
      anorganic bovine bone in the treatment of patients with large periradicular
      lesions of strictly endodontic origin has no beneficial effect on outcome.

PMID- 17517296
TI  - Stereomodel-assisted fibula flap harvest and mandibular reconstruction.
AB  - PURPOSE: To describe a method for stereomodel-assisted fibula flap harvest and
      mandibular reconstruction utilizing multiple fibula bony segments. MATERIALS AND
      METHODS: Stereomodels of the mandible and the fibula were obtained from computed
      tomography scan data. The length of fibula to be harvested was predetermined by
      measurement of the stimulated of existing mandibular defect on the mandibular
      stereomodel. A titanium reconstruction plate was shaped to fit the original
      mandibular contour. The stereomodel fibula was divided into multiple segments and
      the segments were placed on the mandibular stereomodel in the ideal edentulous
      position against the upper dentition and simulate the angular contour of the
      mandible for best comesis. The predetermined bony segments were measured and the
      system was then transferred to the patient in the operation theater using acrylic
      locating splints. RESULTS: Experience with 8 patients (2 primary and 2 secondary
      reconstructions) indicated that a good clinical outcome in terms of mandibular
      contour and positions of the reconstructed segment was possible. The outer facial
      appearance and symmetry were consistently excellent and no instability or
      malposition of the graft segments was encountered. CONCLUSION: Stereomodel
      assisted fibula flap harvest and insertion is a worthwhile attempt at improving
      the results of mandibular reconstruction and deserves further attention.

PMID- 17517297
TI  - Long-term efficacy of carbon dioxide laser resurfacing for facial actinic
      keratosis.
AB  - PURPOSE: To evaluate the efficacy and long-term effectiveness of carbon dioxide
      laser resurfacing in the treatment of patients with facial actinic keratosis.
      PATIENTS AND METHODS: A retrospective chart analysis was conducted of 31 patients
      who underwent full face carbon dioxide laser resurfacing for facial actinic
      keratosis from July 1998 to November 2002. RESULTS: Of 31 patients, 18 (58%) were
      free of lesions at their longest visit. The average actinic keratosis free
      period, excluding 2 deceased patients, was 27.4 months. CONCLUSION: Carbon
      dioxide laser resurfacing is an effective tool in the management of patients with
      facial actinic keratosis.

PMID- 17517298
TI  - Fourteen-year follow-up of a patient-fitted total temporomandibular joint
      reconstruction system.
AB  - PURPOSE: The purpose of this study was to continue the assessment of the safety
      and effectiveness of the Patient-Fitted Total Temporomandibular Joint
      Reconstruction System (now, TMJ Concepts Patient-Fitted Total Temporomandibular
      Joint Reconstruction System, Ventura, CA; previously referred to as Techmedica,
      Camarillo, CA, the CAD/CAM Patient-Fitted Total Temporomandibular Joint
      Reconstruction System). PATIENTS AND METHODS: Questionnaires were mailed to the
      available addresses of 193 patients who had been implanted with Techmedica/TMJ
      Concepts devices between 1990 and 2004. Of 193 recorded addresses, 149 (77.2%)
      were valid, and 44 (22.7%) were returned by the US Postal Service as
      undeliverable. Two (1%) surveys were remailed; both were returned completed. A
      total of 61 (31.6%) surveys were returned properly completed. This represented
      102 devices (41 bilateral, 20 unilateral), with a mean follow-up of 11.4 years
      (standard deviation [SD] 3.0; range, 0 to 14). Subjective data related to pain,
      perception of mandibular function, diet consistency, and current quality of life
      were collected with the use of visual analog scales. Objective measures of
      maximum interincisal opening (MIO) were obtained from direct measurements with
      the Therabite Measuring Scale (Atos Medical, Milwaukee, WI), which was provided
      in the survey along with instructions on its use. RESULTS: Analysis of subjective
      data showed a significant reduction in pain scores and an increase in mandibular
      function and diet consistency scores (P < .001). Analysis of objective data
      showed an improvement in mandibular range of motion after 14 years (P = .02).
      Among all respondents, 85% reported quality of life (QOL) scores that showed
      improvement since baseline. Long-term quality of life improvement scores also
      were found to be statistically related to the number of previous
      temporomandibular joint operations the patient had undergone. CONCLUSIONS:
      Outcome data presented show that the Patient-Fitted Total Temporomandibular Joint
      Reconstruction System continues to be a safe, effective, and reliable long-term
      management modality for the specific patient population surveyed in this study.

PMID- 17517300
TI  - How do feedback and instructions affect the performance of a simulated surgical
      task?
AB  - PURPOSE: This study was conducted to objectively evaluate the effect of feedback
      and instructional material on the acquisition of surgical psychomotor skills for
      a model system based on mandibular fracture repair. MATERIALS AND METHODS: This
      study was a prospective cohort study comprised of students in the preclinical
      years of dental or medical education. The students were divided into 4 groups and
      exposed to different levels of feedback/written instructions (including none) in
      the testing environment. Each subject was given a pair of aluminum bars,
      representing a fractured human mandible, and a standardized set of tools,
      including a fixed length of stainless steel wire to fix the bars together. The
      strength of fixation was measured, using a calibrated testing apparatus, as the
      amount of load that the fixed sample could tolerate to the point of failure. All
      subjects completed 5 successive trials under the same conditions. Descriptive
      statistics were recorded to provide comparisons between groups. Bivariate
      statistics were computed to compare the different study groups; multiple
      comparison testing was used to evaluate differences among the groups. A P value
      <or= .05 was considered statistically significant. RESULTS: The sample was
      comprised of 61 students, divided into 4 groups. The students who received
      neither instructions nor feedback had the lowest average performance scores.
      Those who received both feedback and instructions had the highest average
      performance scores. The students who received instructions only fared better than
      those who received feedback only, but only immediately after receiving
      instructions. Differences between the groups tended to dissipate after a few
      trials. CONCLUSIONS: Written instructions and performance feedback can enhance
      the acquisition of psychomotor skills related to the performance of a complex
      task.

PMID- 17517299
TI  - Oral surgery in patients on anticoagulant treatment without therapy interruption.
AB  - PURPOSE: Conflicting opinions exist in literature concerning the management of
      oral surgery in patients on oral anticoagulants because no consensus on
      perioperative protocols is available, including precise guidelines regarding the
      need for therapy modification or withdrawal. The aim of this study was to
      evaluate bleeding complications associated with oral surgery performed on
      patients on oral anticoagulants without therapy modification or withdrawal but
      following a standardized comprehensive perioperative management protocol.
      PATIENTS AND METHODS: Patients on oral anticoagulant therapy with warfarin and in
      need of oral surgery underwent a thorough general and oral clinical evaluation to
      assess thromboembolic and bleeding risk; 255 subjects who, on the morning of
      surgery, had INR values <or=5.5 were included in the study. An atraumatic
      surgical technique was carried out and all patients received postoperative
      careful instructions. RESULTS: Five cases (1.96%) of bleeding complication were
      observed in patients with moderate to high thromboembolic and bleeding risk.
      CONCLUSION: The findings from this study suggest that a comprehensive
      perioperative management protocol for oral surgery in patients on oral
      anticoagulants including 1) thromboembolic and bleeding risk assessment, 2) an
      atraumatic surgical technique, and 3) postoperative careful instructions, can
      lead to safe and successful results with minimal complications.

PMID- 17517301
TI  - Sensory retraining after orthognathic surgery: effect on patients' perception of
      altered sensation.
AB  - PURPOSE: The primary research hypothesis was that the magnitude and duration of
      the perceived burden from altered sensation reported by patients after bilateral
      sagittal split osteotomy and trauma to the third division of the trigeminal nerve
      are decreased when facial sensory retraining exercises are performed in
      conjunction with standard opening exercises as compared with standard opening
      exercises alone. SUBJECTS AND METHODS: A total of 186 subjects were enrolled in a
      multicenter, double-blind, 2 parallel group-stratified block randomized clinical
      trial. Oral and facial pain, unusual sensations, numbness, and loss of
      sensitivity were scored from "no problem" to "serious problem" before surgery and
      1 month, 3 months, and 6 months after surgery. A proportional odds model for the
      ordered multinomial response was used to compare the responses of the 2 exercise
      groups. RESULTS: The 2 exercise groups did not differ significantly at any
      postsurgical time in terms of perceived problem level from intraoral of facial
      pain. The difference between the 2 groups at each visit was not statistically
      significant for unusual sensations, although the trend was for the sensory
      retraining group to have a higher likelihood of reporting fewer problems. By 6
      months, the likelihood of a subject reporting lower problem or interference level
      related to numbness or decreased lip sensitivity was significantly higher in the
      sensory-retraining group, approximately twice that of the opening exercise-only
      group. CONCLUSIONS: Our results support the premise that a simple noninvasive
      exercise program initiated shortly after orthognathic surgery can lessen the
      objectionable impression of negative altered sensations.

PMID- 17517302
TI  - A review of the effects of expansion of the nasal base on nasal airflow and
      resistance.
AB  - PURPOSE: The purpose of this article is to inform the reader of the current
      literature regarding nasal airflow resistance. The anatomy and physiology of
      nasal airflow resistance will be examined and the known effects of widening of
      the nasal airway upon airflow will be described. MATERIALS AND METHODS: This
      article is a review of the current literature regarding nasal airflow and
      resistance and the effects of widening of the nasal base. No patient data were
      collected. RESULTS: The literature shows that nasal airflow resistance can be
      changed by surgical manipulation and by rapid palatal expansion, but that the
      effects on airflow resistance and future growth and development are
      unpredictable. CONCLUSION: Patients with a maxilla that is constricted in the
      transverse dimension and nasal airflow problems may benefit from expansion of the
      nasal base. The resultant effects upon nasal airflow resistance and subsequent
      growth and development are unpredictable and therefore airflow issues alone may
      not be a primary reason to increase the transverse dimension of the nasal base.

PMID- 17517303
TI  - Lag screw fixation of anterior mandibular fractures: a retrospective analysis of
      intraoperative and postoperative complications.
AB  - PURPOSE: To review, retrospectively, the outcomes of 102 patients who underwent
      lag screw technique fixation of fractures of the anterior mandible. PATIENTS AND
      METHODS: A total of 102 consecutive, skeletally mature patients who have
      undergone open reduction internal fixation for fractures of the anterior mandible
      utilizing the lag screw technique were reviewed. All patients had a clinically
      mobile fracture between the mental foramina of the mandible. The patients were
      followed at usual postoperative intervals with shortest long-term follow-up of 2
      months. Intraoperative and long-term postoperative outcomes including status of
      union, infection, and intraoperative surgical misadventure were recorded.
      RESULTS: Data from the 102 patients showed that there was 1 fixation failure due
      to inappropriate patient selection, 1 nonunion requiring bone grafting, 1 with
      infected screws but with union, 1 with an infected screw and delayed union
      treated conservatively, and 6 with broken drills from intraoperative surgical
      misadventures. CONCLUSIONS: Lag screw osteosynthesis of anterior mandibular
      fractures is a sensitive, facile, predictable, and relatively inexpensive method
      for internal fixation of indicated fractures. As with all methods of rigid
      internal fixation, most failures or complications are the result of operator
      judgment or technique.

PMID- 17517304
TI  - The displaced lower third molar: a literature review and suggestions for
      management.
AB  - PURPOSE: To review the literature associated with displaced lower third molars,
      to introduce a modified method of retrieval of an accidentally displaced lower
      third molar tooth or root fragment, and to recommend rational guidelines for
      management. MATERIALS AND METHODS: A review of the literature was performed to
      record the types of displacements, patient's personal data, imaging used, and the
      surgical approaches with their complications. A modified technique for
      exploration and retrieval is described. RESULTS: Nineteen reports were identified
      and reviewed. Some others could not be translated. In the 32 cases reviewed,
      there were no gender differences and the third and fourth decades of life were
      the most common time for this mishap to occur. Fragments were displaced into 5
      different tissue spaces. The size of the fragments varied, but the whole tooth
      and fragment were displaced with equal frequency. Different methods of recovery
      were used. CONCLUSION: The accidental displacement of a lower third molar during
      attempted extraction is a rare but potentially serious complication. Retrieval
      should be effected as soon as possible. Because of differences in the direction
      of displacement, the size of fragment, delay in retrieval, and tissue reactions,
      no one technique is uniformly applicable. The modified method we suggest appears
      to save time and have few complications.

PMID- 17517305
TI  - Analysis of death certification in patients with early stage oral cavity squamous
      cell carcinoma.
AB  - PURPOSE: Although patients with T1 oral cavity carcinoma have a generally good
      prognosis, there is a significant burden of patients that have locoregional
      recurrence and mortality from early stage disease. The aim of this study was to
      investigate the specific cause of death in patients with T1N0M0 oral cavity
      squamous cell carcinoma (OCSCC) by analysis of death certification. PATIENTS AND
      METHODS: Patients were identified with T1 OCSCC treated over a 15-year period
      between 1986 to 2001 from the Mayo Clinic Tumor Registry. All patients were
      treated by operation without neck dissection or postoperative neoadjuvant therapy
      as the initial method of treatment. On detailed examination of the death
      certificate the leading cause of death was identified along with other clinical
      predictors of death. RESULTS: Two hundred fifty patients were identified and met
      inclusion criteria from the Mayo Clinic Tumor Registry. Of the study group, 8.5%
      and 16% developed local and regional recurrence, respectively, as the first
      recurrence. The majority of recurrences that were amenable to surgery were
      managed by radical resection and postoperative neoadjuvant therapy. Of 85 deaths
      in the study group, 40 death certificates were obtained and reviewed to ascertain
      a specific cause of death. Patients were grouped into death from oral cancer,
      other cancer, or medical disease. Primary cause of death from the death
      certificates available for review included uncontrolled locoregional disease
      (20%), metastatic oral cancer (15%), development of secondary nonoral malignancy
      (15%), and a variety of medical causes (50%). Patient age at the time of
      diagnosis older than 65 had a statistically significant increase in mortality.
      Interestingly, the presence of premorbid medical conditions, history, or
      persistent tobacco and alcohol use did not seem to be related to overall
      mortality. CONCLUSION: Early stage OCSCC continues to portend a poor prognosis.
      Analysis of death certification provides useful information of the specific cause
      of death.

PMID- 17517306
TI  - Virtual reality surgical planning for maxillofacial distraction osteogenesis: the
      role of reverse engineering rapid prototyping and cooperative work.
AB  - PURPOSE: The purpose of this article is the demonstration of virtual reality (VR)
      and rapid prototyping (RP) in surgical planning in maxillofacial surgery. The
      authors emphasize the role of reverse engineering (RE) and RP, suggesting a model
      of cooperative work, with the interaction of maxillofacial surgeons,
      radiologists, and engineers. MATERIALS AND METHODS: Data acquisition is performed
      using computed tomography. The 3D model is the result of RE practices based on
      image segmentation, and the real model is produced via stereolithography. Virtual
      simulations are performed on the 3D model obtained from image segmentation. All
      these stages require the interaction and collaboration of various experts:
      maxillofacial surgeons, radiologists, and RE and RP experts. RESULTS: VR and
      stereolithography models represent a new technology to help the surgeon who has
      to work in cooperation with engineers and radiologists to improve the results in
      surgical planning of maxillofacial distraction. CONCLUSION: When performing the
      VR simulation, surgeons and engineers operate together in order to optimize the
      exploitation of the instruments available. Both VR and RP, with different and
      complementary advantages and limitations, can improve surgical planning
      activities and this is particularly effective when dealing with complex
      anatomical structures in maxillofacial surgery.

PMID- 17517307
TI  - Penetrating injuries to the face: delayed versus primary treatment-
      considerations for delayed treatment.

PMID- 17517308
TI  - Primary treatment of penetrating injuries to the face.

PMID- 17517309
TI  - Myofibroblastic tumor of the lower lip in a patient with X-linked
      hypogammaglobulinemia and isolated growth hormone deficiency: a case report.

PMID- 17517310
TI  - High-grade papillary cystadenocarcinoma of the sublingual gland: a case report.

PMID- 17517311
TI  - Squamous odontogenic tumor causing erosion of the lingual cortical plate in the
      mandible: a report of 2 cases.

PMID- 17517312
TI  - Thrombophlebitis of the sigmoid sinus after tongue piercing: a case report.

PMID- 17517313
TI  - Surgical management of osteoma associated with a familial Gardner's syndrome.

PMID- 17517314
TI  - Transnasal approach to marsupialization of the nasolabial cyst: report of 2
      cases.

PMID- 17517315
TI  - Epidural hemorrhage after removal of a rigid external distraction device.

PMID- 17517316
TI  - Traumatic bone cyst of the condylar region: report of 2 cases.

PMID- 17517317
TI  - Multiple giant cell lesions of the maxillofacial skeleton.

PMID- 17517318
TI  - A case of mucous cyst in the lingual retromolar region.

PMID- 17517319
TI  - Oral sarcoidosis: report of a case and review of literature.

PMID- 17517320
TI  - Mesenchymal chondrosarcoma of the maxilla: case report and literature review.

PMID- 17517321
TI  - Transplantation of alloplastic submandibular glands as not clinically applicable
      treatment for xerostomia.

PMID- 17517323
TI  - Laser for treatment of ranula.

PMID- 17517324
TI  - Abstracts of the 6th International Congress of the Baltic Medico-Legal
      Association, Vilnius, Lithuania.

PMID- 17517325
TI  - Effect of chronic ethanol administration on disposition of ethanol and its
      metabolites in rat.
AB  - We studied the effects of chronic alcohol intake on the disposition of alcohol
      and its metabolites in the rat. We used male Wistar rats for all of the
      experiments in this study. Using a pair-feeding process, rats were fed a liquid
      diet containing alcohol or without alcohol for 6 weeks. Ethanol solutions (0.5,
      1.0, 1.5, and 2.0 g/kg body weight [BW]) were administered as a bolus,
      intravenously. We then measured blood ethanol and acetate concentrations.
      Simultaneous multiline fitting was performed using mean blood alcohol
      concentration (BAC)-time curves fitted to the one-compartment open model with
      parallel first-order and Michaelis-Menten elimination kinetics. At low doses
      (0.5, 1.0, and 1.5 g/kgBW), no differences were observed between the alcohol
      group and the control group with respect to ethanol elimination rate, area under
      the curve of ethanol (AUC(EtOH)), and mean residence time of ethanol (MRT(EtOH)).
      At higher doses (2.0 g/kgBW), ethanol elimination rate in the alcohol group was
      significantly higher than in the control group (P<.5%). These findings were also
      substantiated by corresponding changes in AUC(EtOH) and MRT(EtOH). At low doses,
      no differences were observed between the alcohol group and the control group with
      respect to plateau concentration of acetate (AcT) (concentration of steady
      state=C(ss)AcT), area under the curve of AcT (AUC(AcT)), and mean residence time
      of AcT (MRT(AcT)). However, at higher doses, although there were no differences
      in C(ss)AcT, both AUC(AcT) and MRT(AcT) were significantly lower in the alcohol
      group when compared to the control group (P<.5%). Chronic alcohol consumption
      increases ethanol oxidation and AcT metabolism in rats, as observed at high blood
      alcohol concentrations (BACs). These effects were observed at BACs of 3.5-4.5
      mg/ml, and were not observed at lower doses. Thus, with general alcohol
      consumption, interindividual differences and intra-individual changes in alcohol
      metabolism may not take into account increased or accelerated metabolism due to
      alcohol tolerance.

PMID- 17517327
TI  - Radiotherapy dose fractionation, access and waiting times in the countries of the
      UK in 2005.
AB  - AIMS: The Royal College of Radiologists has published a review of the evidence
      base for radiotherapy dose fractionation. We modelled the implications of changes
      in practice on radiotherapy demand and compared it with current activity, access
      and waiting times across the countries of the UK. MATERIALS AND METHODS: We
      collected data on diagnosis, dose fractionation and waiting times on all patients
      in the UK starting a course of radiotherapy in the week commencing 26 September
      2005. Excluding skin cancer, 2610 patients were prescribed 34,194 fractions.
      RESULTS: Radiotherapy access rates were 38% in England, 43% in Scotland and 37%
      in Wales. These are all lower than the 52% of cancer patients recommended by
      modelling. To increase access to the recommended level, a 33% increase in
      activity is required across the UK. For each of 13 cancer diagnoses, we modelled
      optimum fractionation and compared it with current practice. To deliver the dose
      fractionation with the best evidence base, a further increase in activity of 37%
      is required. To take account of both access and optimal fractionation, the two
      factors should be multiplied (1.33x1.37=1.82) giving an overall increase of 82%
      for the UK. This would require 53,741 fractions per million population annually.
      The exact value depends on the cancer incidence in each country, but should be
      compared with current activity of 28,040 in England, 39 584 in Scotland and
      31,228 in Wales. Limited capacity is reflected in waiting times. The percentage
      of patients exceeding the maximum recommended wait of 28 days for radical or
      adjuvant postoperative radiotherapy was 55% in England, 44% in Scotland and 74%
      in Wales. CONCLUSIONS: To secure adequate access to treatment and optimal dose
      fractionation, substantial increases in radiotherapy activity of 92% in England,
      61% in Scotland and 97% in Wales are required. Achieving this will require a
      planned programme of investment in staff, training and equipment.

PMID- 17517328
TI  - Is the alpha/beta value for prostate tumours low enough to be safely used in
      clinical trials?
AB  - There has been an intense debate over the past several years on the relevant
      alpha/beta value that could be used to describe the fractionation response of
      prostate tumours. Previously it has been assumed that prostate tumours have high
      alpha/beta values, similar to most other tumours and the early reacting normal
      tissues. However, the proliferation behaviour of the prostate tumours is more
      like that of the late reacting tissues, with slow doubling times and low
      alpha/beta values. The analyses of clinical results carried out in the past few
      years have indeed suggested that the alpha/beta value that characterises the
      fractionation response of the prostate is low, possibly even below the 3 Gy
      commonly assumed for most late complications, and hence that hypofractionation of
      the radiation treatment might improve the therapeutic ratio (better control at
      the same or lower complication rate). However, hypofractionation might also
      increase the complication rates in the surrounding late responding tissues and if
      their alpha/beta value is not larger that of prostate tumours it could even lead
      to a decrease in the therapeutic ratio. Therefore, the important question is
      whether the alpha/beta value for the prostate is lower than the alpha/beta values
      of the surrounding late responding tissues at risk. This paper reviews the
      clinical and experimental data regarding the radiobiological differential that
      might exist between prostate tumours and the late normal tissues around them.
      Several prospective hypofractionated trials that have been initiated recently in
      order to determine the alpha/beta value or the range of values that describe the
      fractionation response of prostate tumours are also reviewed. In spite of several
      confounding factors that interfere with the derivation of a precise value, it
      seems that most data support a trend towards lower alpha/beta values for prostate
      tumours than for rectum or bladder.

PMID- 17517326
TI  - Functional gene expression differences between inbred alcohol-preferring and -non
      preferring rats in five brain regions.
AB  - The objective of this study was to determine if there are innate differences in
      gene expression in selected CNS regions between inbred alcohol-preferring (iP)
      and -non-preferring (iNP) rats. Gene expression was determined in the nucleus
      accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU), and
      hippocampus (HIPP) of alcohol-naive adult male iP and iNP rats, using Affymetrix
      Rat Genome U34A microarrays (n = 6/strain). Using Linear Modeling for Microarray
      Analysis with a false discovery rate threshold of 0.1, there were 16 genes with
      differential expression in the ACB, 54 in the AMYG, 8 in the FC, 24 in the CPU,
      and 21 in the HIPP. When examining the main effect of strain across regions, 296
      genes were differentially expressed. Although the relatively small number of
      genes found significant within individual regions precluded a powerful analysis
      for over-represented Gene Ontology categories, the much larger list resulting
      from the main effect of strain analysis produced 17 over-represented categories
      (P < .05), including axon guidance, gliogenesis, negative regulation of
      programmed cell death, regulation of programmed cell death, regulation of synapse
      structure function, and transmission of nerve impulse. Co-citation analysis and
      graphing of significant genes revealed a network involved in the neuropeptide Y
      (NPY) transmitter system. Correlation of all significant genes with those located
      within previously established rat alcohol QTLs revealed that of the total of 313
      significant genes, 71 are located within such QTLs. The many regional and overall
      gene expression differences between the iP and iNP rat lines may contribute to
      the divergent alcohol drinking phenotypes of these rats.

PMID- 17517329
TI  - Perimicrovillar membranes promote hemozoin formation into Rhodnius prolixus
      midgut.
AB  - Rhodnius prolixus is a hematophagous insect that ingests large quantities of
      blood in each blood-feeding session. This ingested blood provides important
      nutrients to sustain the insect's oogenesis and metabolic pathways. During the
      digestive process, however, huge amounts of heme are generated as a consequence
      of the hemoglobin breakdown. Heme is an extremely dangerous molecule, since it
      can generate reactive oxygen species in the presence of oxygen that impair the
      normal metabolism of the insect. Part of the hemoglobin-derived heme can
      associate with the perimicrovillar membranes (PMM) in the gut lumen of R.
      prolixus; in this study we demonstrate the participation of the PMM in a heme
      detoxification process. These membranes were able to successfully induce heme
      aggregation into hemozoin (Hz). Heme aggregation was not dependent on the
      erythrocyte membranes, since the contribution of these membranes to the process
      was negligible, demonstrating that the ability to induce heme aggregation is a
      feature of the PMM, possibly representing a pre-adaptation of the hemipterans to
      feeding on blood.

PMID- 17517330
TI  - Cloning and functional characterization of the Anopheles albimanus DMT1/NRAMP
      homolog: implications in iron metabolism in mosquitoes.
AB  - In addition to its wide role in metabolism, iron in insects has been implicated
      in vitellogenesis and the immune response. The NRAMP family comprises a well
      conserved family of divalent cation transporters in metazoans. To gain insight on
      the role of NRAMP in Anopheles albimanus, we cloned a cDNA encoding a 571-residue
      protein (AnaNRAMP) with the structural features defining the NRAMP family.
      AnaNRAMP mRNA induced (59)Fe(2+) incorporation when injected into Xenopus
      oocytes. Western blot analysis revealed that AnaNRAMP is expressed in the head,
      midgut and at high levels in Malpighian tubules of unfed female mosquito. Upon
      blood feeding, AnaNRAMP levels were reduced in the midgut whereas they increased
      in the Malpighian tubules. Using immuno-localization by transmission electron
      microscopy, AnaNRAMP was localized in the membrane of the intra-cellular
      concretions or spherites of the Malpighian tubule principal cells. Taken
      together, our results suggest an important role of AnaNRAMP in iron transport and
      indicate a role of the mosquito Malpighian tubule as an important organ for iron
      homeostasis.

PMID- 17517331
TI  - Only one esterase of Drosophila melanogaster is likely to degrade juvenile
      hormone in vivo.
AB  - Previously we identified juvenile hormone esterase (JHE) from Drosophila
      melanogaster by the criteria that it showed both appropriate developmental
      expression and kinetics for juvenile hormone (JH). We also noted three further
      esterases of D. melanogaster with some JHE-like characteristics, such as a GQSAG
      active site motif, a particular amphipathic helix, or close phylogenetic
      relationship with other JHEs. In this study, these JHE-like enzymes were
      expressed in vitro and their kinetic parameters compared with those of the
      previously identified JHE. Despite considerable phylogenetic distance between
      some of the esterases, they could all hydrolyse racemic JHIII. However, only the
      previously identified JHE had kinetic parameters (K(M) and k(cat)) towards
      various forms of JH (racemic or individual isomers of JHIII, JHII, JHI, and
      methyl farnesoate) consistent with a physiological role in JH regulation.
      Furthermore, only this JHE showed a preference for artificial substrates with
      acyl chain lengths similar to that of JH. This suggests that there is probably
      only one physiologically functional JHE in D. melanogaster but multiple esterases
      with JH esterase activity. Genomic comparisons of the selective JHE across 11
      other Drosophila species showed a single orthologue in 10 of them but Drosophila
      willistoni has 16 full-length copies, five of them with the GQSAG motif and
      amphipathic helix.

PMID- 17517332
TI  - Dynamics of insecticide resistance alleles in house fly populations from New York
      and Florida.
AB  - The frequency of insecticide-resistance alleles for two genes (Vssc1 and CYP6D1)
      was studied in field collected populations of house flies from two different
      climates. While the frequency of these resistance alleles in flies at dairies
      from four states has recently been reported, there is no information on the
      relative change of these allele frequencies over time. House flies were collected
      during the 2003-2004 season from New York and Florida before the first
      application of permethrin, during the middle of the field season, after the final
      application, and again the following spring (following months without permethrin
      use). Bioassay results indicated that homozygous susceptible and extremely
      resistant flies were rare, while moderately and highly resistant individuals were
      relatively common at all times in both states. The frequency of resistance
      alleles at the New York dairy rose during the season and declined over the
      winter, suggesting an overwintering fitness cost associated with these alleles.
      The super-kdr allele was detected for the first time in North America at the end
      of 2003. In Florida the frequency of the resistance alleles did not increase
      during the spray season or decrease during the winter, suggesting there is
      substantial immigration of susceptible alleles to the Florida dairy and no
      overwintering fitness cost associated with resistance alleles in this climate.
      Resistance to permethrin correlated well with the frequency of the Vssc1 and
      CYP6D1 resistance alleles in flies from New York, but not as well in the
      population from Florida. This suggests there may be a new resistance mechanism or
      allele evolving in Florida.

PMID- 17517333
TI  - Characterization of Aedes Dredd: a novel initiator caspase from the yellow fever
      mosquito, Aedes aegypti.
AB  - Caspases play an essential role during programmed cell death in all metazoans.
      These enzymes are cysteine proteases and comprise a multi-gene family with more
      than a dozen mammalian family members. Although caspases have been characterized
      in many animals, including Drosophila melanogaster, little is known about the
      caspases that exist in mosquitoes. Here we describe the identification and
      characterization of Aedes Dredd (AeDredd), a novel caspase in the yellow fever
      mosquito, Aedes aegypti. AeDredd contains two N-terminal death effector domains
      and the well conserved caspase catalytic domain. Multiple sequence alignments and
      functional substrate assays of recombinant protein suggest that AeDredd is an
      orthologue of Drosophila Dredd and human caspase-8, both central effectors of the
      death receptor-mediated apoptotic pathway. AeDredd exhibits substrate specificity
      most similar to human caspase-8. AeDredd transcripts were found in all
      developmental stages with highest expression in early pupae. Within adults,
      AeDredd was found in all the tissues examined, with the highest transcript levels
      detected in fat body tissues. This is the first functional characterization of a
      death domain-containing caspase in an insect vector of human disease, and will
      initiate studies on the role of apoptosis in the innate immune response of
      vectors towards intracellular parasites such as viruses.

PMID- 17517335
TI  - Lipid metabolism in Rhodnius prolixus (Hemiptera: Reduviidae): role of a midgut
      triacylglycerol-lipase.
AB  - The utilization of dietary lipids was studied in adult females of Rhodnius
      prolixus with the use of radiolabeled triacylglycerol (TAG). It was shown that
      (3)H-triolein, when added to blood meal, was hydrolyzed to free fatty acids in
      the posterior midgut lumen. Subsequently, free fatty acids were absorbed by
      posterior midgut epithelium and used in the synthesis of phospholipids,
      diacylglycerol (DAG) and TAG. Phospholipids, DAG and free fatty acids were then
      found in hemolymph, from where they were rapidly cleared, and label was found in
      the fat body, mainly associated with TAG. Radioactive lipids, especially TAG and
      phospholipids, also accumulated in the ovaries. The TAG-lipase activities of
      posterior midgut luminal content and tissue were characterized by incubation of
      these samples with (3)H-triolein in the presence of the detergent Triton X-100
      and determination of the amounts of released radioactive free fatty acids. Under
      the conditions employed here, the release of free fatty acids was proportional to
      the incubation time and to the amount of sample obtained from insect midgut
      (enzyme source) that was added. TAG-lipase activities were affected by pH and
      posterior midgut tissue showed optimum activity around pH 7.0-7.5, but the
      luminal content had the highest activities as pH decreased. Differences in
      activities were observed according to calcium concentration in the medium. TAG
      lipase activities were also affected by the concentration of NaCl and were
      activated in the presence of increasing salt concentrations. These activities
      were inhibited by phenylmethylsulphonyl fluoride (PMSF). On the second day after
      blood meal, when digestion is very intense, TAG-lipase activities were maximal
      and then gradually decreased.

PMID- 17517334
TI  - Specific transcriptional responses to juvenile hormone and ecdysone in
      Drosophila.
AB  - Previous studies have shown that ecdysone (E), and its immediate downstream
      product 20-hydroxyecdysone (20E), can have different biological functions in
      insects, suggesting that E acts as a distinct hormone. Here, we use Drosophila
      larval organ culture in combination with microarray technology to identify genes
      that are transcriptionally regulated by E, but which show little or no response
      to 20E. These genes are coordinately expressed for a brief temporal interval at
      the onset of metamorphosis, suggesting that E acts together with 20E to direct
      puparium formation. We also show that E74B, pepck, and CG14949 can be induced by
      juvenile hormone III (JH III) in organ culture, and that CG14949 can be induced
      by JH independently of protein synthesis. In contrast, E74A and E75A show no
      response to JH in this system. These studies demonstrate that larval organ
      culture can be used to identify Drosophila genes that are regulated by hormones
      other than 20E, and provide a basis for studying crosstalk between multiple
      hormone signaling pathways.

PMID- 17517336
TI  - Characterisation of functional and insecticidal properties of a recombinant
      cathepsin L-like proteinase from flesh fly (Sarcophaga peregrina), which plays a
      role in differentiation of imaginal discs.
AB  - ScathL is a cathepsin L-like cysteine proteinase from Sarcophaga peregrina (flesh
      fly), which is involved in differentiation of imaginal discs, through proteolysis
      of components of basement membranes. An expression system based on the
      methylotrophic yeast Pichia pastoris was used to produce recombinant ScathL.
      Although the expression construct contained the full proprotein coding sequence
      for ScathL, the proprotein was only detected in culture supernatant at early
      stages of expression by Western blotting. The purified recombinant protein
      contained only a polypeptide similar to mature ScathL, as a result of
      autocatalytic processing. After activation by reducing agents, the enzyme
      hydrolysed the cathepsin L substrate Z-Phe-Arg-AMC, with optimal activity at pH
      5.5. ScathL showed decreasing activity with increasing ionic strength above 0.3M
      NaCl, and lost activity irreversibly at pH > or = 7.5. The enzyme showed limited
      activity towards protein substrates, digesting only to large fragments. ScathL
      was insecticidal towards larvae of the tomato moth, Lacanobia oleracera,
      following injection into the haemolymph. It caused melanisation, although no
      evidence of extensive proteolysis in haemolymph or gut was observed. Production
      of a inactive mutant form of ScathL showed that enzyme activity was necessary for
      the complete proprotein processing observed during production as a recombinant
      protein, and for insecticidal activity.

PMID- 17517337
TI  - Functional characterization of a desaturase from the tobacco hornworm moth
      (Manduca sexta) with bifunctional Z11- and 10,12-desaturase activity.
AB  - The pheromone blend produced by the tobacco hornworm moth (Manduca sexta) (L.)
      female is unusually complex and contains two conjugated dienals and trienals
      together with two monounsaturated alkenals. Here, we describe the identification
      and construction of two genes encoding MsexKPSE and MsexAPTQ desaturases from a
      cDNA library prepared from the total RNA of the M. sexta pheromone gland. The
      MsexKPSE desaturase shares a high degree of similarity with Delta(9)-desaturases
      from different moth species. The functional expression of MsexAPTQ desaturase in
      Saccharomyces cerevisiae followed by a detailed GC-MS analysis of fatty acid
      methyl esters (FAME) and their derivatized products and gas-phase Fourier
      transform infrared (FTIR) spectroscopy of the extracted FAME confirms that this
      enzyme is a bifunctional Z-Delta(11)-desaturase. MsexAPTQ desaturase catalyses
      the production of Z11-hexadecenoate (Z11-16) and Z10E12- and E10E12
      hexadecadienoates (Z10E12-16) via 1,4-desaturation of the Z11-16 substrate. The
      stereochemistry of 1,4-desaturation and formation of isomers is discussed.

PMID- 17517338
TI  - Ligand binding by recombinant domains from insect ecdysone receptors.
AB  - The ligand binding domains (LBDs) from the EcR and USP proteins of four insect
      pests (Lucilia cuprina, Myzus persicae, Bemisia tabaci, Helicoverpa armigera)
      were purified as recombinant heterodimers. The K(d) values for [(3)H]-ponasterone
      A binding by LBD heterodimers that included the hinge regions (i.e., DE/F
      heterodimers) ranged 0.7-2.5 nM, with K(i) values for ecdysteroid and
      dibenzoylhydrazine ligands ranging from 0.1 nM to >448 microM. The K(d) and K(i)
      values for a recombinant H. armigera LBD heterodimer that lacked D-regions (i.e.,
      an E/F heterodimer) were approximately 4 times higher than those for its DE/F
      counterpart. Rate constants were estimated for the L. cuprina LBD heterodimer. A
      fluorescein-inokosterone conjugate (K(i)~40 nM) was used to develop a novel
      binding assay based on fluorescence polarization. This assay, which ranked the
      affinity of competitor ecdysteroids in the same order as the [(3)H]-ponasterone A
      binding assay, is well suited to high-throughput screening. Ponasterone A had a
      higher affinity than muristerone A for the recombinant hemipteran LBD
      heterodimers, whereas the reverse was true for the recombinant dipteran one. The
      same preference was observed when these ligands were tested as inducers of
      ecdysone receptor-controlled gene expression in transfected mammalian cells. The
      binding data obtained in vitro using recombinant LBD heterodimers reflects the
      ability of agonists to induce transgene expression in recombinant mammalian
      cells, and can also reflect their efficacy as larvicides.

PMID- 17517339
TI  - Actin cytoskeleton as a putative target of the neem limonoid Azadirachtin A.
AB  - Limonoids isolated from the Indian neem tree (Azadirachta indica) have been
      gaining global acceptance in agricultural applications and in contemporary
      medicine for their myriad but discrete properties. However, their mode of action
      is still not very well understood. We have studied the mode of action of
      Azadirachtin A, the major limonoid of neem seed extracts, using Drosophila
      melanogaster as the model system. Azadirachtin A induces moderate-to-severe
      phenotypes in different tissues in a dose-dependent manner. At the cellular
      level, Azadirachtin A induces depolymerization of Actin leading to arrest of
      cells and subsequently apoptosis in a caspase-independent manner. Azadirachtin A
      induced phenotypes were rescued by the over-expression of Cyclin E in a tissue
      dependent manner. Cyclin E, which caused global rescue of Azadirachtin A-induced
      phenotypes, also effected rearrangement of the actin filaments. These results
      suggest that probably actin is a target of Azadirachtin A activity.

PMID- 17517340
TI  - In silico approach of azadirachtin binding with actins.
AB  - In silico docking analysis reported here suggests that insect cellular
      cytoskeletal beta-actin could be the target of Azadirachtin A (Aza-the principle
      bioactive compound of neem seeds). The best docking energy of -40.09 kcal/mol at
      8.73 A RMSD and predicted hydrogen bond between Arg210 and carboxymethyl group of
      Aza accompanied with seven hydrophobic interactions in the proposed binding site
      strongly support this hypothesis. This is of specific interest due to the non
      affinity of Aza to mammalian beta-actins under the same set of conditions,
      although beta-actins across the species are highly conserved. Our results show
      that few scattered amino acid changes have caused significant steric hindrance in
      the binding pocket for mammalian beta-actin, causing a reverse orientation of
      Aza. These results suggest a model to support the recently observed biological
      effects caused by Aza in Drosophila cytoskeletal elements and explain why Aza is
      highly specific to insects than mammals.

PMID- 17517341
TI  - Remote Active Monitoring in Patients with Heart Failure (RAPID-RF): design and
      rationale.
AB  - BACKGROUND: Heart failure (HF) ambulatory disease management programs appear to
      offer the greatest benefit to HF patients at highest risk, defined as having New
      York Heart Association (NYHA) functional Class III or IV symptoms. The Latitude
      Patient Management System is the first HF management tool to use wireless
      telemetry present in a cardiac resynchronization therapy defibrillator (CRT-D)
      device that is linked to remotely collect blood pressure and weight measures,
      permitting a single transmission reporting device data. Potential advantages of
      this system include ease of data transmissions, correlation among measures of HF
      status, arrhythmic events, and device performance. However, the use and ultimate
      utility of these combined features for patient management are untested. METHODS
      AND RESULTS: The Remote Active Monitoring in Patients with Heart Failure (RAPID
      RF) study is a multicenter registry that will enroll up to 1000 patients on the
      Latitude Patient Management System from approximately 100 centers. The primary
      objective is to examine physician responses to Latitude Active Monitoring data
      alerts by assessing alert-related medical interventions. Minimum follow-up will
      be 3 months after implant with a maximum follow-up time of 24 months after
      implant. CONCLUSIONS: The RAPID-RF study will provide important preliminary data
      on how remotely collected HF and arrhythmic surveillance data alter the
      management of HF patients with CRT-D devices.

PMID- 17517342
TI  - Association of low serum levels of apolipoprotein A-I with adverse outcomes in
      patients with nonischemic heart failure.
AB  - BACKGROUND: There is extensive evidence that low serum levels of high-density
      lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) predict a worse
      prognosis in patients with ischemic heart disease. This study examined whether
      apoA-I levels may also provide prognostic information in patients with
      nonischemic heart failure. METHODS AND RESULTS: A prospective follow-up study was
      performed in 117 consecutive patients with nonischemic heart failure for a period
      of < or = 36 months until the first occurrence of 1 of the following clinical
      events: all-cause death, cardiac death, and hospitalization with worsening heart
      failure. Serum levels of apoA-I were measured by immunoturbidimetry. A clinical
      event occurred during follow-up in 28 (24%) patients. A multivariate Cox
      proportional hazards analysis showed that lower apoA-I levels (< 103 mg/dL:
      determined by a receiver-operating characteristic analysis) were significantly
      associated with an adverse outcome that was independent of creatinine clearance,
      HDL cholesterol levels, and brain natriuretic peptide levels. ApoA-I was
      inversely correlated with levels of C-reactive protein and fibrinogen, known
      inflammatory predictors of poor prognosis in heart failure. CONCLUSIONS: Low
      levels of apoA-I are independently associated with an adverse prognosis in
      patients with nonischemic heart failure. ApoA-I may play a beneficial role in
      nonischemic heart failure partly through an anti-inflammatory action.

PMID- 17517343
TI  - Relationship between heart failure and lipids: the paradigm continues to evolve.

PMID- 17517344
TI  - VE/VCO2 slope in older heart failure patients with normal versus reduced ejection
      fraction compared with age-matched healthy controls.
AB  - BACKGROUND: Oxygen consumption (VO2) has previously been used for prognosis and
      risk stratification in patients with heart failure. More recent research has
      introduced VE/VCO2 slope as a prognostic measure. Risk of mortality is thought to
      increase when VE/VCO2 slope values are greater than 34. Therefore, the purpose of
      this study was to cross-sectionally examine VE/VCO2 slope in systolic heart
      failure (SHF) and diastolic heart failure (DHF) as well as age-matched healthy
      controls. METHODS AND RESULTS: Maximal graded exercise tests were conducted on
      147 patients (59 DHF, 60 SHF, and 28 controls) using a bicycle ergometer. Breath
      by-breath expired gas analysis was performed using a commercially available
      system with on-line computer calculations. VE/VCO2 slope was calculated from a
      regression line of minute ventilation and carbon dioxide production. One-way
      analysis of covariance with a Bonferroni post hoc test and Pearson correlations
      were used for statistical analysis. VE/VCO2 slope was significantly higher in SHF
      when compared to both DHF (37 +/- 8 vs. 34 +/- 7, P = .03) and controls (37 +/- 8
      vs. 32 +/- 5, P = .002). No significant difference was observed between DHF and
      healthy controls (34 +/- 7 vs. 32 +/- 5, P = .52). Additional analysis resulted
      in significant correlations between VO2 and VE/VCO2 slope in systolic heart
      failure patients (r = -0.40, P = .002); however, there was no significant
      relationships in diastolic heart failure patients (r = -0.09, P = .49) or in
      controls (r = 0.13, P = .50). CONCLUSIONS: VE/VCO2 slope is significantly higher
      in patients with SHF compared with DHF and healthy controls.

PMID- 17517345
TI  - Chronotropic incompetence in adolescents and adults with congenital heart disease
      after cardiac surgery.
AB  - BACKGROUND: Chronotropic incompetence (CI) is one of the major problems in adults
      with congestive heart. Little is known about CI in adults with congenital heart
      disease (ACHD) after cardiac surgery. The purpose of our study was to investigate
      the presence and risk factors of CI in ACHD patients. METHODS AND RESULTS:
      Clinical and echocardiographic data, NT-pro brain natriuretic peptide (N-BNP),
      and peak oxygen uptake (VO2peak) during spiroergometry were obtained in 345
      consecutive ACHD patients. CI was defined as the failure to achieve > or = 80% of
      the predicted maximal heart rate. A total of 117 (34%) of study patients
      fulfilled the CI criterion. These patients were in a higher New York Heart
      Association class (1.7 +/- 0.06 versus 1.4 +/- 0.03, P < .0001; mean +/- SEM),
      had significantly higher N-BNP levels (230 +/- 31 versus 121 +/- 10 pg/mL, P <
      .0001) and a more pronounced impairment of VO2peak (23.8 +/- 0.6 versus 28.4 +/-
      0.5 mL x kg x min, P < .0001) than those without CI. Elevated odds ratios for CI
      were found in patients with a single ventricle (4.03), Mustard operation for
      transposition of the great arteries (3.11), and aortic coarctation (2.14).
      CONCLUSIONS: Our results indicate that CI in ACHD patients is a frequent problem
      and is related to the severity of the heart failure as measured by symptom
      assessment (New York Heart Association class), plasma N-BNP level and peak oxygen
      uptake.

PMID- 17517346
TI  - Effect of chronic changes in heart rate on congestive heart failure.
AB  - BACKGROUND: Heart rate can affect cardiac function, but the importance of rates
      lower than 100 paced beats per minute is unknown. We therefore sought to evaluate
      the impact of different heart rates on ejection fraction, 6-minute walk, and peak
      oxygen consumption (VO2) in heart failure patients. METHODS AND RESULTS: We
      studied 13 pacemaker-dependent New York Heart Association Class III patients with
      ejection fraction <40%, age 66 +/- 13. Eligible patients included those pacing at
      least 75% of the time at a lower set rate of 60 ppm. This was a 3-period
      randomized blinded crossover study. Patients were assigned to pace at 60, 75, or
      90 ppm (with rate responsivity to 20 ppm above the lower rate) for 2 months at
      each setting. At the end of each period, ejection fraction (by nuclear
      ventriculography) and exercise tolerance (by peak VO2 and 6-minute walk) were
      assessed. Ejection fraction, peak VO2, and 6-minute walk distance were
      significantly different among the 3 heart rates. All 3 were depressed at 90 ppm.
      A heart rate of 90 also led to more clinical deterioration and premature
      discontinuation from that period. CONCLUSIONS: Pacing at a heart rate of 90 led
      to lower ejection fraction, VO2, 6-minute walk distance and clinical evidence of
      worsening heart failure as compared with slower heart rates.

PMID- 17517347
TI  - Amino terminal B-type natriuretic peptide, renal function, and prognosis in acute
      heart failure: a hospital cohort study.
AB  - BACKGROUND: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a
      valuable diagnostic and prognostic test in heart failure (HF). Limited
      information is available concerning its use in patients with renal failure, in
      whom dependence on renal clearance may negatively affect its performance. METHODS
      AND RESULTS: We evaluated influence of renal function on NT-proBNP levels and on
      its prognostic value after hospital discharge in 283 acute HF patients. Admission
      and discharge NT-proBNP levels were higher in patients with decreased estimated
      glomerular filtration rate (eGFR). In these patients discharge NT-proBNP above
      median was associated to occurrence of death or readmission at 6 months (hazard
      ratio [HR] 2.53, 95% confidence interval [CI] 1.27-5.03); in patients with normal
      eGFR, a trend to this association was found (HR 1.64, CI 0.98-2.76). Decrease in
      NT-proBNP less than 30% of baseline was associated to outcome in patients with
      normal eGFR (HR 2.68, CI 1.54-4.68) and decreased eGFR (HR 2.54, CI 1.49-4.33).
      CONCLUSIONS: Acute HF patients with renal failure have higher NT-proBNP levels
      than those with normal renal function. Discharge NT-proBNP has long-term
      prognostic value in HF patients with renal dysfunction. NT-proBNP variations
      during hospitalization provide additional prognostic information either in
      patients with normal or reduced eGFR.

PMID- 17517348
TI  - Validation of remote cardiopulmonary examination in patients with heart failure
      with a videophone-based system.
AB  - BACKGROUND: The aim of this study was to evaluate feasibility and accuracy of a
      videophone-based system for remote cardiopulmonary examination of patients with
      heart failure. METHODS AND RESULTS: Fifty patients were examined by 2
      cardiologists, 1 with a conventional stethoscope and 1 remotely with a videophone
      based method, employing an electronic stethoscope and transmitting through an
      integrated services digital network line. During both sessions, the cardiologists
      filled out a 27-item questionnaire, which was then compared; concordance between
      standard and remote examination was evaluated. In 92% of patients, electronic and
      acoustic auscultation concurred. Only in 3 patients (4%) did teleauscultation not
      permit a correct interpretation of lung examination. In one patient, bilateral
      fine crepitant rales were not detected during teleauscultation. Conversely, in
      the second, patient bilateral fine crepitant rales were recognized during
      teleauscultation, which were not confirmed during real-life auscultation. In the
      third nonconcordant patient, moderate-degree wheezing was not detected during
      teleauscultation. Fine crepitant rales were present at the lungs lower fields in
      12 and wheezing in 3 additional patients, and were always correctly identified
      during teleauscultation. Overall, sensitivity, specificity, positive, and
      negative predictive value of remote lung auscultation were 88%, 97%, 94%, and
      94%, respectively. CONCLUSIONS: Remote cardiopulmonary examination appears as a
      feasible method for assessing patients with heart failure. Telestethoscopy can
      therefore be reliably used in the context of comprehensive telecare programs.

PMID- 17517349
TI  - Lack of long-term benefits of a 6-month heart failure disease management program.
AB  - BACKGROUND: Heart failure (HF) represents a major burden on the health care
      system, causing repeated hospitalizations and numerous emergency department (ED)
      visits. In a 6-month randomized study of a multidisciplinary HF clinic, we have
      previously shown decreased hospital readmissions and improved quality of life.
      Despite these encouraging results, it is unknown if these beneficial effects are
      sustained. METHODS AND RESULTS: To assess long-term recurrent ED visits,
      readmissions, and mortality among HF patients who were discharged after a 6-month
      intensive HF management program (HFMP). Of the 230 subjects (New York Heart
      Association Class II-IV) who were initially randomized to standard follow-up care
      or to a HFMP for 6 months, 190 were studied retrospectively for long-term
      evaluation. Long-term data was obtained from the Quebec administrative health
      databases. We compared the intervention and control groups for the number of
      recurrent ED visits, hospital readmissions, and all-cause deaths. After a mean
      follow-up of 2.8 +/- 1.7 years, there was no difference in the composite end
      point of all-cause death, hospital admissions, and ED visits between those
      patients initially in the HFMP group and the controls. After multivariable
      adjustment, there was no difference in the composite primary endpoint (HR 1.01,
      95% CI: 0.75-1.37) or in the secondary end point of all-cause death alone (HR
      1.09, 95%CI:0.69-1.72) between those initially assigned to the HF clinic and
      those receiving usual care. CONCLUSIONS: For severely ill patients, the clinical
      and resource benefits of a 6-month HFMP are not sustained upon program cessation.
      Further research into the benefits of long-term HFMP is required.

PMID- 17517350
TI  - Effect of exercise training on autonomic derangement and neurohumoral activation
      in chronic heart failure.
AB  - BACKGROUND: In chronic heart failure (CHF), persistent autonomic derangement and
      neurohumoral activation cause structural end-organ damage, decrease exercise
      capacity, and reduce quality of life. Beneficial effects of pharmacotherapy and
      of exercise training in CHF have been documented at various functional and
      structural levels. However, pharmacologic treatment can not yet reduce autonomic
      derangement and neurohumoral activation in CHF to a minimum. Various studies
      suggest that exercise training is effective in this respect. METHODS AND RESULTS:
      After reviewing the available evidence we conclude that exercise training
      increases baroreflex sensitivity and heart rate variability, and reduces
      sympathetic outflow, plasma levels of catecholamines, angiotensin II,
      vasopressin, and brain natriuretic peptides at rest. CONCLUSIONS: Exercise
      training has direct and reflex sympathoinhibitory beneficial effects in CHF. The
      mechanism by which exercise training normalizes autonomic derangement and
      neurohumoral activation is to elucidate for further development of CHF-related
      training programs aimed at maximizing efficacy while minimizing workload.

PMID- 17517351
TI  - Effect of cardiac resynchronization therapy on myocardial gene expression in
      patients with nonischemic dilated cardiomyopathy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves echocardiographic
      measures of ventricular structure and function in the failing heart. To determine
      whether or not these changes are representative of true biologic reverse
      ventricular remodeling or simply an artifact of an improved contraction pattern,
      we evaluated changes in myocardial gene expression typical of reverse remodeling
      before and after chronic CRT. METHODS AND RESULTS: Optimally medically treated
      patients with nonischemic heart failure meeting standard clinical criteria for
      CRT were enrolled. Before implantation of a CRT device, baseline echocardiogram
      and endomyocardial biopsies were obtained. These studies were repeated after 6
      months of CRT. Using quantitative reverse-transcriptase polymerase chain
      reaction, the amount of messenger RNA for selected genes regulating contractile
      function (sarcoplasmic reticulum Ca2+ ATPase, alpha- and beta-myosin heavy chain
      [MHC] isoforms, phospholamban [PLB]), and pathologic hypertrophy (beta-MHC and
      atrial natriuretic peptide [ANP]) was determined from biopsy samples. Changes in
      gene expression (baseline to 6 months) were determined and correlated to changes
      in echocardiographic remodeling parameters. Ten patients were enrolled in the
      study, with 7 completing both baseline and follow-up biopsies and
      echocardiograms. On average, a significant increase was observed in alpha-MHC and
      PLB gene expression from baseline to 6 months (P = .016 for both). Beta-MHC
      levels tended to decrease with CRT (P = .078). Increased alpha-MHC levels
      correlated best with decreases in left ventricular end-diastolic dimension (P =
      .073, r = -0.71) and reductions in mitral regurgitation. No significant
      correlation between ejection fraction and gene expression was found. CONCLUSIONS:
      These changes in myocardial gene expression support the occurrence of reverse
      remodeling during chronic CRT. The changes are similar to those reported
      previously with beta-blockade, but were seen on top of standard drug therapies
      for heart failure.

PMID- 17517352
TI  - Left atrial reverse remodeling in dogs with moderate and advanced heart failure
      treated with a passive mechanical containment device: an echocardiographic study.
AB  - BACKGROUND: Assessment of global left ventricular (LV) remodeling is important in
      evaluating the efficacy of pharmacologic and device therapies for the treatment
      of chronic heart failure (HF). The effects of pharmacologic or device therapies
      on global left atrial (LA) remodeling in HF, although also important, are not
      often examined. We showed that long-term therapy with the Acorn Cardiac Support
      Device (CSD), a passive mechanical ventricular containment device, prevents or
      reverses LV remodeling in dogs with HF. This study examined the effects of the
      CSD on global LA remodeling in dogs with moderate and advanced HF. METHODS AND
      RESULTS: Studies were performed in 24 dogs with coronary microembolization
      induced HF. Of these, 12 had moderate HF (ejection fraction, EF 30% to 40%) and
      12 advanced HF (EF < or = 25%). In each group, the CSD was implanted in 6 dogs
      and the other 6 served as controls. Dogs were followed for 3 months in the
      moderate group and 6 months in the advanced HF group. LA maximal volume (LAVmax),
      LA volume at the onset of the p-wave (LAVp), LA minimal volume (LAVmin), LA
      active emptying volume (LAAEV), and LA active emptying fraction (LAAEF) were
      measured from 2-dimensional echocardiograms obtained before CSD implantation and
      at the end of the treatment period. Treatment effect (delta) comparisons between
      CSD-treated dogs and controls showed that CSD therapy significantly decreased LA
      volumes (deltaLAVmax: 3.33 +/- 0.70 vs. -2.87 +/- 1.31 mL, P = .002; 7.77 +/-
      1.76 versus -0.37 +/- 0.87 mL, P = .002) and improved LA function (deltaLAAEF: 
      6.00 +/- 1.53 versus 1.85 +/- 1.32%, P = .003; -2.39 +/- 1.10 versus 3.13 +/-
      1.66%, P = .02) in the moderate HF and advanced HF groups, respectively.
      CONCLUSIONS: Progressive LA enlargement and LA functional deterioration occurs in
      untreated dogs with HF. Monotherapy with the CSD prevents LA enlargement and
      improves LA mechanical function in dogs with moderate and advanced HF indicating
      prevention or reversal of adverse LA remodeling.

PMID- 17517354
TI  - Sleep and metabolism: bringing pieces of the jigsaw together.

PMID- 17517353
TI  - Hypertrophy and heart failure in mice overexpressing the cardiac sodium-calcium
      exchanger.
AB  - BACKGROUND: The cardiac sodium-calcium exchanger (NCX1) is a key sarcolemmal
      protein for the maintenance of calcium homeostasis in the heart. Because heart
      failure is associated with increased expression of NCX1, heterozygous (HET) and
      homozygous (HOM) transgenic mice overexpressing NCX1 were developed and
      evaluated. METHODS AND RESULTS: The NCX1 transgenic mice display 2.3-fold (HET)
      and 3.1-fold (HOM) increases in exchanger activity from wild-type (WT) mice.
      Functional information was obtained by echocardiography and catheterizations
      before and after hemodynamic stress from pregnancy, treadmill exercise or
      transaortic constriction (TAC). HET and HOM mice exhibited hypertrophy and
      blunted responses with beta-adrenergic stimulation. Postpartum mice from all
      groups were hypertrophied, but only the HOM mice exhibited premature death from
      heart failure. HOM mice became exercise intolerant after 6 weeks of daily
      treadmill running. After 21 days TAC, HET, and HOM mice exhibited significant
      contractile dysfunction and 15% to 40% mortality with clinical evidence of heart
      failure. CONCLUSIONS: Hemodynamic stress results in a compensated hypertrophy in
      WT mice, but NCX1 transgenic mice exhibit decreased contractile function and
      heart failure in proportion to their level of NCX1 expression. Thus exchanger
      overexpression in mice leads to abnormal calcium handling and a decompensatory
      transition to heart failure with stress.

PMID- 17517355
TI  - A systematic review of valerian as a sleep aid: safe but not effective.
AB  - Valerian is an herb that is widely available in a variety of commercial
      preparations and is commonly used as a sleep aid. A recent systematic review and
      meta-analysis of valerian concluded that evidence in support of the effectiveness
      of the herb was inconclusive. Therefore, in an effort to more closely examine
      this issue, a systematic review was conducted to examine the evidence on the
      efficacy of valerian as a sleep aid with specific attention to the type of
      preparations tested and the characteristics of the subjects studied. A
      comprehensive search of studies investigating valerian was conducted through
      computerized databases and hand searches of reference lists. Standardized forms
      were used to summarize findings and standardized criteria were used to assess
      study quality. Out of 592 articles initially identified, a total of 36 articles
      describing 37 separate studies met criteria for review: 29 controlled trials
      evaluated for both efficacy and safety, and eight open-label trials evaluated for
      safety only. Most studies found no significant differences between valerian and
      placebo either in healthy individuals or in persons with general sleep
      disturbance or insomnia. None of the most recent studies, which were also the
      most methodologically rigorous, found significant effects of valerian on sleep.
      Overall, the evidence, while supporting that valerian is a safe herb associated
      with only rare adverse events, does not support the clinical efficacy of valerian
      as a sleep aid for insomnia.

PMID- 17517356
TI  - Exercise, sleep and cytokines: is there a relation?
AB  - Physical exercise is a modality of non-pharmacological treatment for sleep
      disorders. Contradicting results are still found in studies of the effect of
      exercise on sleep. Among the substances that have been described as sleep
      modulators, cytokines produced during the recovery period after an acute exercise
      session are very important. Various studies have verified that physical exercise
      may alter the plasma concentration of the many pro-inflammatory cytokines that
      may in turn modulate sleep. A number of factors seem to mediate this effect of
      exercise, including duration, intensity, and form of exercise, in addition to
      temperature and metabolic alterations. The mechanisms through which exercise
      promotes alterations in sleep architecture remain to be clarified. Researchers
      speculate that many hormones and substances produced by metabolism may affect
      sleep. Therefore, the object of this review is to discuss the effects of exercise
      and cytokines on sleep, and the relation between these two sleep-regulating
      components, raising the hypothesis that the alterations in sleep promoted by
      exercise are mediated by cytokines, which, by increasing the nREM sleep phase,
      would stimulate the regenerating characteristics of sleep.

PMID- 17517358
TI  - Preventing pediatric mass casualty events.

PMID- 17517359
TI  - Testing hospital disaster communication plan has immense value.

PMID- 17517360
TI  - The value of support for aid workers in complex emergencies: a phenomenological
      study.
AB  - BACKGROUND: More disasters worldwide are now classified as complex emergencies,
      thereby increasing the threat to life and limb and potentially increasing the
      psychosocial impact of the experience for aid workers. OBJECTIVE: This study
      examines the concept of support as perceived by aid workers who had recent
      experience in complex emergencies. METHOD: Using a phenomenological approach, 6
      professional aid workers were interviewed about their experience. RESULTS: Aid
      workers who work in complex emergencies do not feel supported at the pre
      deployment, during deployment, and after deployment phases. Failure to provide
      this support may cause disappointment, reduced self-worth, anger with the
      organization, and feeling of lack of achievement regarding self and the mission.
      CONCLUSION: While the study may be limited by the volunteer sample and potential
      bias in data collection, the findings reiterate a proverbial but important issue
      in relation to aid relief staff in complex emergencies.

PMID- 17517361
TI  - Emergency department staff preparedness for mass casualty events involving
      children.
AB  - BACKGROUND: In recent years, the World Health Organization in general, and Israel
      in particular, have dealt with mass casualty events (MCEs) resulting from
      terrorism. Children are the casualties in many of these events-a reality that
      forces hospitals to prepare to deal with such a scenario. A literature review
      designed to identify unique recommendations regarding pediatric MCEs highlights
      both a lack of existing training programs and uncertainty on the part of health
      care staff when dealing with these events. OBJECTIVES: The purpose of the study
      was to examine the preparedness level of emergency department staff to deal with
      MCEs involving pediatric casualties. The study included 104 physicians and nurses
      working in, or responding to, the emergency department at a hospital in Israel.
      METHOD: The study included a 41-item questionnaire examining perception,
      approaches, and staff knowledge regarding dealing with pediatric MCEs versus
      those involving adults. The reliability of all sections of the questionnaire
      ranged between Chronbach's alpha coefficient 0.6 alpha-0.94. RESULTS: The
      preparedness levels for MCEs involving children were found to be low. Study
      participants ranked the likelihood of a pediatric MCE lower than one involving
      adults, while ranking significantly higher (P = .000) their ability to cope
      mentally and the knowledge and skills required when treating adults involved in
      MCEs. While nurses ranked higher than physicians regarding their knowledge and
      skills in dealing with pediatric MCE casualties, the level of knowledge for MCEs
      involving children was low in all subjects. Staff agreement for the parent of an
      MCE victim to be present during treatment was medium-low. IMPLICATIONS: On the
      basis of these findings, additional research involving a larger number of
      individuals and hospitals is indicated to determine if these results are
      consistent throughout the region.

PMID- 17517362
TI  - Will first-responders show up for work during a pandemic? Lessons from a smallpox
      vaccination survey of paramedics.
AB  - BACKGROUND: The presence of H5N1 influenza in Southeast Asia has reawakened fears
      of a worldwide influenza pandemic of the sort that occurred in 1918. It is
      estimated that up to 1.9 million people in the United States could die if such an
      outbreak occurs. It is unlikely that a vaccine for a pandemic strain will be
      available quickly enough to protect first-responders. Similar concerns existed in
      2002 when the United States attempted to vaccinate first-responders against
      smallpox, a potential biologic weapon. METHOD: We conducted a survey of one group
      of first-responders, paramedics, to determine if fear of infection would
      compromise their ability to care for persons potentially infected with smallpox.
      RESULTS: Three hundred paramedics were given the survey, and 95 (32%) responded.
      More than 80% of paramedics polled would not remain on duty if there were no
      vaccine and no protective gear. Even if protective gear was available but the
      vaccine was unavailable, only 39% of respondents would remain on duty. Finally,
      although 91% of paramedics would remain on duty if they were fully protected,
      this number falls to 38% if the respondent believed that his or her immediate
      family was not protected. The results of this survey are relevant to current
      concerns about an influenza pandemic. Every effort must be made to protect first
      responders from pandemic influenza and educate them about it.

PMID- 17517363
TI  - A mass casualty incident involving children and chemical decontamination.
AB  - Mass casualty incidents involving contaminated children are a rare but ever
      present possibility. In this article we outline one such event that resulted in
      53 pediatric patients and 3 adults presenting to the emergency department of a
      children's hospital for decontamination and treatment. We pay special attention
      to the training that allowed this responses to occur. We also outline the
      institutional response with emphasis on incident command, communication, and
      resource utilization. Specific lessons learned are explored in detail. Finally,
      we set forth a series of recommendations to assist other institutions should they
      be called upon to care for and decontaminate pediatric patients.

PMID- 17517364
TI  - Mass medical evacuation: Hurricane Katrina and nursing experiences at the New
      Orleans airport.
AB  - Hurricane Katrina, a category 4 storm, struck the U.S. Gulf states in late
      August, 2005, resulting in the most costly and second most deadly natural
      disaster in recent United States history. The storm and subsequent flooding due
      to levee failure necessitated the evacuation of 80% of the city of New Orleans'
      484,674 residents. Most of the city's hospitals and other health care resources
      were destroyed or inoperable. The hurricane devastated many communities,
      stranding people in hospitals, shelters, homes, and nursing homes. Nurses and
      other health care providers deployed to New Orleans to provide medical assistance
      experienced substantial challenges in making triage and treatment decisions for
      patients whose numbers far exceeded supplies and personnel. This article
      describes the experiences and solutions of nurses and other personnel from 3
      Disaster Medical Assistance Teams assigned to the New Orleans airport responsible
      for perhaps the most massive patient assessment, stabilization, and evacuation
      operation in U.S. history. As the frequency of disasters continues to rise, it is
      imperative that the nursing profession realize its value in the disaster arena
      and continually take leadership roles.

PMID- 17517366
TI  - Comparative expression of tristetraprolin (TTP) family member transcripts in
      normal human tissues and cancer cell lines.
AB  - The tristetraprolin (TTP) family of tandem zinc finger proteins comprises three
      members in man and most other mammals, with a fourth expressed in rodents. In
      mice, gene disruption of TTP itself leads to a systemic inflammatory syndrome
      that is mediated in large part by over-expression of tumor necrosis factor alpha
      (TNF). This increased expression is secondary to stabilization of the TNF mRNA in
      the TTP KO mice, a finding that led to the characterization of TTP as an mRNA
      binding protein that can promote the removal of the poly(A) tail from selected
      mRNAs and facilitate their nucleolytic destruction. The other human family
      members behave similarly to TTP in over-expression studies of transfected cells,
      but gene disruption experiments have implicated them in different physiological
      processes. In the present study, we developed a real-time PCR assay for all three
      human family members that allowed for comparative measurements of all three
      family members in the same tissues and cells. We used this assay to quantitate
      expression levels of all three transcripts in a variety of normal human tissues,
      as well as in the ;;NCI 60", a well characterized panel of human tumor cell
      lines. Although studies in fibroblasts and macrophages derived from knockout mice
      have failed to demonstrate compensatory expression of the family members in terms
      of transcript levels, it remains possible that the different family members can
      function as ;;TTP equivalents" in certain physiological or pathological
      circumstances.

PMID- 17517365
TI  - Molecular and cellular mechanisms of the anabolic effect of intermittent PTH.
AB  - Intermittent administration of parathyroid hormone (PTH) stimulates bone
      formation by increasing osteoblast number, but the molecular and cellular
      mechanisms underlying this effect are not completely understood. In vitro and in
      vivo studies have shown that PTH directly activates survival signaling in
      osteoblasts; and that delay of osteoblast apoptosis is a major contributor to the
      increased osteoblast number, at least in mice. This effect requires Runx2
      dependent expression of anti-apoptotic genes like Bcl-2. PTH also causes exit of
      replicating progenitors from the cell cycle by decreasing expression of cyclin D
      and increasing expression of several cyclin-dependent kinase inhibitors. Exit
      from the cell cycle may set the stage for pro-differentiating and pro-survival
      effects of locally produced growth factors and cytokines, the level and/or
      activity of which are known to be influenced by PTH. Observations from
      genetically modified mice suggest that the anabolic effect of intermittent PTH
      requires insulin-like growth factor-I (IGF-I), fibroblast growth factor-2 (FGF
      2), and perhaps Wnts. Attenuation of the negative effects of PPAR gamma may also
      lead to increased osteoblast number. Daily injections of PTH may add to the pro
      differentiating and pro-survival effects of locally produced PTH related protein
      (PTHrP). As a result, osteoblast number increases beyond that needed to replace
      the bone removed by osteoclasts during bone remodeling. The pleiotropic effects
      of intermittent PTH, each of which alone may increase osteoblast number, may
      explain why this therapy reverses bone loss in most osteoporotic individuals
      regardless of the underlying pathophysiology.

PMID- 17517367
TI  - Slower eating rate reduces the food intake of men, but not women: implications
      for behavioral weight control.
AB  - This study tested a central tenet of behavioral weight control: does slower
      eating rate reduce food intake and positively affect appetite ratings. This study
      used direct behavioral observation of participants' (n=48; 25BMI35) eating
      behavior using Universal Eating Monitors. Food intake and ratings of "desire to
      eat" (collected each minute during meals) were represented as a function of time.
      Based on an acclimation meal, participants' eating rate was modified by
      instructing them to eat a bite of food when prompted by a computer, which
      generated three types of meals: (1) baseline (eating rate was the same as the
      acclimation meal), (2) reduced-rate (eating rate was reduced by 50%), and (3)
      combined-rate (eating rate at the beginning of the meal was identical to that of
      the acclimation meal, subsequently eating rate was reduced by 50%). All meals
      were ad libitum. Slower eating rate during the reduced-rate and combined-rate
      meals resulted in less food intake compared to the baseline meal for men, but not
      women. Ratings of desire to eat, normalized for the amount of food consumed, were
      lower during the combined-rate meal for men and women. Thus, this basic premise
      of behavioral weight control was supported for men, but not for women.

PMID- 17517368
TI  - AFM imaging reveals the tetrameric structure of the TRPC1 channel.
AB  - We have determined the subunit stoichiometry of the transient receptor potential
      C1 (TRPC1) channel by imaging isolated channels using atomic force microscopy
      (AFM). A frequency distribution of the molecular volumes of individual channel
      particles had two peaks, at 170 and 720 nm(3), corresponding with the expected
      sizes of TRPC1 monomers and tetramers, respectively. Complexes were formed
      between TRPC1 channels and antibodies against a V5 epitope tag present on each
      subunit. The frequency distribution of angles between pairs of bound antibodies
      had two peaks, at 88 degrees and 178 degrees. This result again indicates that
      the channel assembles as a tetramer.

PMID- 17517369
TI  - Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function.
AB  - The expression of tumor suppressor gene DBC2 causes certain breast cancer cells
      to stop growing [M. Hamaguchi, J.L. Meth, C. Von Klitzing, W. Wei, D. Esposito,
      L. Rodgers, T. Walsh, P. Welcsh, M.C. King, M.H. Wigler, DBC2, a candidate for a
      tumor suppressor gene involved in breast cancer, Proc. Natl. Acad. Sci. USA 99
      (2002) 13647-13652]. Recently, DBC2 was found to participate in diverse cellular
      functions such as protein transport, cytoskeleton regulation, apoptosis, and cell
      cycle control [V. Siripurapu, J.L. Meth, N. Kobayashi, M. Hamaguchi, DBC2
      significantly influences cell cycle, apoptosis, cytoskeleton, and membrane
      trafficking pathways. J. Mol. Biol. 346 (2005) 83-89]. Its tumor suppression
      mechanism, however, remains unclear. In this paper, we demonstrate that DBC2
      suppresses breast cancer proliferation through down-regulation of Cyclin D1
      (CCND1). Additionally, the constitutional overexpression of CCND1 prevented the
      negative impact of DBC2 expression on their growth. Under a CCND1 promoter, the
      expression of CCNE1 exhibited the same protective effect. Our results indicate
      that the down-regulation of CCND1 is an essential step for DBC2's growth
      suppression of cancer cells. We believe that this discovery contributes to a
      better understanding of DBC2's tumor suppressor function.

PMID- 17517370
TI  - The effects of differential gene expression on coding sequence features: analysis
      by one-way ANOVA.
AB  - It is well-established that non-random patterns in coding DNA sequence (CDS)
      features can be partially explained by translational selection. Recent extensions
      of microarray and proteomic expression data have stimulated many genome-wide
      investigations of the relationships between gene expression and various CDS
      features. However, only modest correlations have been found. Here we introduced
      the one-way ANOVA, a more powerful extension of previous grouping methods, to re
      examine these relationships at the whole genome scale for Saccharomyces
      cerevisiae, where genome-wide protein abundance has been recently quantified. Our
      results clarify that coding sequence features are inappropriate for use as genome
      wide estimators for protein expression levels. This analysis also demonstrates
      that one-way ANOVA is a powerful and simple method to explore the influence of
      gene expression on CDS features.

PMID- 17517371
TI  - Crystallographic study on the interaction of L-lactate oxidase with pyruvate at
      1.9 Angstrom resolution.
AB  - L-Lactate oxidase (LOX) from Aerococcus viridans catalyzes the oxidation of L
      lactate to pyruvate by the molecular oxygen and belongs to a large family of 2
      hydroxy acid-dependent flavoenzymes. To investigate the interaction of LOX with
      pyruvate in structural details and understand the chemical mechanism of flavin
      dependent L-lactate dehydrogenation, the LOX-pyruvate complex was crystallized
      and the crystal structure of the complex has been solved at a resolution of 1.90
      Angstrom. One pyruvate molecule bound to the active site and located near N5
      position of FMN for subunits, A, B, and D in the asymmetric unit, were
      identified. The pyruvate molecule is stabilized by the interaction of its
      carboxylate group with the side-chain atoms of Tyr40, Arg181, His265, and Arg268,
      and of its keto-oxygen atom with the side-chain atoms of Tyr146, Tyr215, and
      His265. The alpha-carbon of pyruvate is found to be 3.13 Angstrom from the N5
      atom of FMN at an angle of 105.4 degrees from the flavin N5-N10 axis.

PMID- 17517373
TI  - Anti-parallel membrane topology of two components of EbrAB, a multidrug
      transporter.
AB  - EbrAB is a multidrug-resistance transporter in Bacillus subtilis that belongs to
      the small multidrug resistance, and requires two polypeptides of both EbrA and
      EbrB, implying that it functions in the hetero-dimeric state. In this study, we
      investigated the transmembrane topologies of EbrA and EbrB. Various single
      cysteine mutants were expressed in Escherichia coli cells, and the efflux
      activity was measured. Only mutants having a high activity were used for the
      topology experiments. The reactivity of a membrane impermeable NEM-fluorescein
      against the single cysteine of these fully functional mutants was examined when
      this reactive fluorophore was applied either from the outside or both sides of
      the cell membrane or in the denatured state. The results clearly showed that EbrA
      and EbrB have the opposite orientation within the membrane or an anti-parallel
      configuration.

PMID- 17517372
TI  - Regional differences in prostaglandin E2 and nitric oxide production in the knee
      meniscus in response to dynamic compression.
AB  - Injury or loss of the knee meniscus is associated with altered joint stresses
      that lead to progressive joint degeneration. The goal of this study was to
      determine if dynamic mechanical compression influences the production of
      inflammatory mediators by meniscal cells. Dynamic compression increased
      prostaglandin E2 (PGE(2)) and nitric oxide (NO) production over a range of stress
      magnitudes (0.0125-0.5 MPa) in a manner that depended on stress magnitude and
      zone of tissue origin. Inner zone explants showed greater increases in PGE(2) and
      NO production as compared to outer zone explants. Meniscal tissue expressed NOS2
      and NOS3 protein, but not NOS1. Mechanically induced NO production was blocked by
      NOS inhibitors, and the non-selective NOS inhibitor L-NMMA augmented PGE(2)
      production in the outer zone only. These findings suggest that the meniscus may
      serve as an intra-articular source of pro-inflammatory mediators, and that
      alterations in the magnitude or distribution of joint loading could significantly
      influence the production of these mediators in vivo.

PMID- 17517374
TI  - Increased TRPA1, TRPM8, and TRPV2 expression in dorsal root ganglia by nerve
      injury.
AB  - Thermosensitive TRP channels display unique thermal responses, suggesting
      distinct roles mediating sensory transmission of temperature. However, whether
      relative expression of these channels in dorsal root ganglia (DRG) is altered in
      nerve injury is unknown. We developed a multiplex ribonuclease protection assay
      (RPA) to quantify rat TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8 RNA levels in
      DRG. We used the multiplex RPA to measure thermosensitive TRP channel RNA levels
      in DRG from RTX-treated rats (300 microg/kg) or rats with unilateral sciatic
      nerve chronic constriction injury (CCI). TRPV1 and TRPA1 RNA were significantly
      decreased in DRG from RTX-treated rats, indicating functional colocalization of
      TRPA1 and TRPV1 in sensory nociceptors. In DRG from CCI rats, TRPA1, TRPV2, and
      TRPM8 RNA showed slight but significant increases ipsilateral to peripheral nerve
      injury. Our findings support the hypothesis that increased TRP channel expression
      in sensory neurons may contribute to mechanical and cold hypersensitivity.

PMID- 17517375
TI  - The densovirus of Periplaneta fuliginosa (PfDNV) as an insect vector for
      persistent foreign gene expression in vivo.
AB  - An infectious clone of the Periplaneta fuliginosa densovirus (PfDNV) has been
      constructed and the PfDNV genome can rescue from the plasmid and replicate as the
      wild-type virus in nymphs of P. fuliginosa. To investigate the ability of the
      cloned PfDNV genome to be used as a stable and persistent expression vector, we
      constructed seven recombinant plasmids in which the GFP reporter gene was
      inserted into the genome of PfDNV. When these recombinant constructs were
      transfected into hosts, the GFP was expressed efficiently in every clone.
      Southern blot analysis revealed that recombinant plasmids had integrated into
      host genome. Infectious recombinant virions could be produced from plasmids in
      which the GFP gene was downstream of and in frame with the NS3 and NS1 coding
      regions. These results indicate that PfDNV genome can be used as an insect vector
      for the transfer and persistent expression of an exogenous gene.

PMID- 17517376
TI  - Effect of 15-lipoxygenase metabolites, 15-(S)-HPETE and 15-(S)-HETE on chronic
      myelogenous leukemia cell line K-562: reactive oxygen species (ROS) mediate
      caspase-dependent apoptosis.
AB  - Growth inhibitory effects of 15-lipoxygenase-1 [13-(S)-HPODE and 13-(S)-HODE] and
      15-lipoxygenase-2 [15-(S)-HPETE and 15-(S)-HETE] (15-LOX-1 and LOX-2) metabolites
      and the underlying mechanisms were studied on chronic myeloid leukemia cell line
      (K-562). The hydroperoxy metabolites, 15-(S)-HPETE and 13-(S)-HPODE rapidly
      inhibited the growth of K-562 cells by 3h with IC(50) values, 10 and 15microM,
      respectively. In contrast, the hydroxy metabolite of 15-LOX-2, 15-(S)-HETE,
      showed 50% inhibition only at 40microM by 6h and 13-(S)-HODE, hydroxy metabolite
      of 15-LOX-1, showed no significant effect up to 160microM. The cells exposed to
      10microM of 15-(S)-HPETE and 40microM of 15-(S)-HETE showed typical apoptotic
      features like release of cytochrome c, caspase-3 activation and PARP-1 (poly(ADP)
      ribose polymerase-1) cleavage. A flow cytometry based DCFH-DA analysis and
      inhibitory studies with DPI, a pharmacological inhibitor of NADPH oxidase, NAC (N
      acetyl cysteine) and GSH revealed that NADPH oxidase-mediated generation of ROS
      is responsible for caspase-3 activation and subsequent induction of apoptosis in
      the K-562 cell line.

PMID- 17517377
TI  - Discovery of Trp-Nle-Tyr-Met as a novel agonist for human formyl peptide receptor
      like 1.
AB  - Formyl peptide receptor-like 1 (FPRL1) is a structural homologue of FPR, which
      binds chemotactic peptides as small as three amino acids (e.g., fMet-Leu-Phe,
      fMLF) and activates potent bactericidal functions in neutrophils. In comparison,
      FPRL1 ligands include peptides of 6-104 amino acids, such as Trp-Lys-Tyr-Met-Val
      [d]Met (WKYMVm) and other synthetic peptides. To determine the core peptide
      sequence required for FPRL1 activation, we prepared various analogues based on
      WKYMVm and evaluated their bioactivities in an FPRL1-transfected cell line.
      Although substitution of d-Met(6) resulted in loss of activity, removal of Val(5)
      together with d-Met(6) produced a peptide that retained most of the bioactivities
      of the parent peptide. The resulting peptide, WKYM, represents a core structure
      for an FPRL1 ligand. Further substitution of Lys(2) with Nle slightly improved
      the potency of the tetrapeptide, which selectively activates FPRL1 over FPR.
      Based on these structure-activity relationship studies, we propose a model in
      which the modified tetrapeptide Trp-Nle-Tyr-Met (WNleYM) binds to FPRL1 through
      aromatic interactions involving the side chains of Trp(1) and Tyr(3), hydrophobic
      interaction of Nle(2), and the thio-based hydrogen bonding of Met(4), with the
      respective residues in FPRL1 which have not been identified. The identification
      of the core sequence of a potent peptide agonist provides a structural basis for
      future design of peptidomimetics as potential therapeutic agents for FPRL1
      related disorders.

PMID- 17517378
TI  - Interaction between the catalytic and modifier subunits of glutamate-cysteine
      ligase.
AB  - Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the glutathione
      (GSH) biosynthesis pathway. This enzyme is a heterodimer, comprising a catalytic
      subunit (GCLC) and a regulatory subunit (GCLM). Although GCLC alone can catalyze
      the formation of l-gamma-glutamyl-l-cysteine, its binding with GCLM enhances the
      enzyme activity by lowering the K(m) for glutamate and ATP, and increasing the
      K(i) for GSH inhibition. To characterize the enzyme structure-function
      relationship, we investigated the heterodimer formation between GCLC and GCLM, in
      vivo using the yeast two-hybrid system, and in vitro using affinity
      chromatography. A strong and specific interaction between GCLC and GCLM was
      observed in both systems. Deletion analysis indicated that most regions, except a
      portion of the C-terminal region of GCLC and a portion of the N-terminal region
      of GCLM, are required for the interaction to occur. Point mutations of selected
      amino acids were also tested for the binding activity. The GCLC
      Cys248Ala/Cys249Ala and Pro158Leu mutations enzyme showed the same strength of
      binding to GCLM as did wild-type GCLC, yet the catalytic activity was
      dramatically decreased. The results suggest that the heterodimer formation may
      not be dependent on primary amino-acid sequence but, instead, involves a complex
      formation of the tertiary structure of both proteins.

PMID- 17517379
TI  - Synthesis and biological evaluation of galactofuranosyl alkyl thioglycosides as
      inhibitors of mycobacteria.
AB  - As part of our research interest directed toward the development of
      antimycobacterial agents, we have investigated compounds based on galactofuranose
      (Galf), an essential cell wall component of mycobacteria. The objective of this
      study was to explore structure activity relationships of Galf thioglycosides with
      straight chain and branched aglycons. Acylated Galf 9-heptadecyl thioglycoside
      was prepared by Lewis acid-catalyzed thioglycosidation of 1,2,3,5,6-penta-O-acyl
      D-galactofuranose with 9-heptadecanethiol, and subsequently converted to the
      corresponding sulfone using m-CPBA. Both Galf 9-heptadecyl thioglycoside and
      sulfone displayed in vitro inhibition (MIC) of the growth of Mycobacterium
      smegmatis below 5 microg/mL, while Galf 1-octyl thioglycoside gave no inhibition
      at or below 32 microg/mL.

PMID- 17517380
TI  - Synthesis of 7-O-galloyl-D-sedoheptulose.
AB  - A facile synthetic approach to 7-O-galloyl-D-sedoheptulose (1), a natural product
      with notable immunosuppressant activity, was developed. The starting material,
      2,7-anhydro-d-sedoheptulose (2), was converted in three steps into 1,3,4,5-tetra
      O-benzyl-d-sedoheptulose (5), a key intermediate that allows specific
      functionalization at C-7 of the sedoheptulpyranose. After regioselective
      esterification of 5 with 3,4,5-tri-O-benzyl galloyl acid, followed by catalytic
      debenzylation (Pd-C), 1 was obtained in an overall yield of 60%. The
      spectroscopic data and TLC behavior of 1 were found to be identical to that of
      the natural product.

PMID- 17517381
TI  - Synthesis of sporiolide B from D-glucal.
AB  - A total synthesis of the 12-membered ring natural macrolide, sporiolide B, was
      achieved from D-glucal in 17 steps with 4.8% overall yield. The required
      stereochemical configuration at C-3 and C-5 in sporiolide B was easily introduced
      by applying a Mitsunobu reaction on the chiral template D-glucal. Yamaguchi
      esterification and ring closing metathesis greatly improved the access to the
      target compound.

PMID- 17517382
TI  - The synthesis of 2-, 3-, 4- and 6-O-alpha-D-glucopyranosyl-D-galactopyranose, and
      their evaluation as nutritional supplements for pre-term infants.
AB  - Four methods have been screened for the synthesis of some alpha-D
      glucopyranosides, with the recently reported (Mukaiyama) combination of 2,3,4,6
      tetra-O-benzyl-alpha-D-glucopyranosyl iodide and triphenylphosphine oxide being
      the most successful, especially in the diastereoselectivity exhibited. The alpha
      D-glucopyranosides so obtained have been deprotected to yield 2-, 3-, 4- and 6-O
      alpha-D-glucopyranosyl-D-galactopyranose. Only the last disaccharide showed any
      hydrolysis by alpha-glycosidases but this success was not emulated by mucosal
      extracts from the small intestine of the pig.

PMID- 17517383
TI  - N-acetyl-D-glucosamine substituted calix[4]arenes as stimulators of NK cell
      mediated antitumor immune response.
AB  - A series of calixarenes substituted with 2-acetamido-2-deoxy-beta-D-glucopyranose
      linked by a thiourea spacer was prepared and tested for binding activity to
      heterogeneously expressed activation receptors of the rat natural killer cells
      NKR-P1, and the receptor CD69 (human NK cells, macrophages). In the case of NKR
      P1, the binding affinity of beta-D-GlcNAc-substituted calixarenes carrying two or
      four sugar units was in a good agreement with the inhibitory potencies of the
      linear chitooligomers (chitobiose to chitotetraose) reported previously. The
      influence of GlcNAc substitution of the calixarene skeleton on binding affinity
      for CD69 receptor was more profound and the 5,11,17,23-tetrakis[N-(2-acetamido-2
      deoxy-beta-D-glucopyranosyl)-thioureido]-25,26,27,28-tetrapropoxycalix[4]arene
      (cone) (1) proved to be the best CD69 ligand identified to date. Lower GlcNAc
      substitution led to dramatic decrease of the binding activity (by about 1.5 order
      of magnitude per one GlcNAc unit). The immunostimulating activity results with
      the newly synthesized GlcNAc tetramers on calixarene scaffolds exhibited
      stimulation of natural cytotoxicity of human PBMC in concentrations 10(-4) and
      10(-8)M. These calix-sugar compounds were superior to the previously tested PAMAM
      GlcNAc(8)5.

PMID- 17517384
TI  - Conformational behaviour of glycomimetics: NMR and molecular modelling studies of
      the C-glycoside analogue of the disaccharide methyl beta-D-galactopyranosyl-(1-
      >3)-beta-D-glucopyranoside.
AB  - The conformational behaviour of the C-glycoside beta-C-Gal-(1-->3)-beta-Glc-OMe
      (1) has been studied using a combination of molecular mechanics and NMR
      spectroscopy (proton-proton coupling constants and nuclear Overhauser effects).
      It is shown that the C-disaccharide populates two distinctive conformational
      families in solution, the normal syn-psi conformation, which is the predominating
      conformation of parent O-glycoside 2, and the anti-psi conformation, which has
      not been detected for the O-disaccharide.

PMID- 17517385
TI  - Gene expression profile class prediction using linear Bayesian classifiers.
AB  - Due to recent advances in DNA microarray technology, using gene expression
      profiles, diagnostic category of tissue samples can be predicted with high
      accuracy. In this study, we discuss shortcomings of some existing gene expression
      profile classification methods and propose a new approach based on linear
      Bayesian classifiers. In our approach, we first construct gene-level linear
      classifiers to identify genes that provide high class-prediction accuracies,
      i.e., low error rates. After this screening phase, starting with the gene that
      offers the lowest error rate, we construct a multi-dimensional linear classifier
      by incorporating next best-performing genes, until the prediction error becomes
      minimum or 0, if possible. When we compared classification performance of our
      approach against prediction analysis of microarrays (PAM) and support vector
      machines (SVM) based approaches, we found that our method outperforms PAM and
      produces comparable results with SVM. In addition, we observed that the gene
      selection scheme of PAM could be misleading. Albeit SVM achieves relatively
      higher prediction performance, it has two major disadvantages: Complexity and
      lack of insight about important genes. Our intuitive approach offers competing
      performance and also an efficient means for finding important genes.

PMID- 17517386
TI  - An automatic analysis method for detecting and eliminating ECG artifacts in EEG.
AB  - An automated method for detecting and eliminating electrocardiograph (ECG)
      artifacts from electroencephalography (EEG) without an additional synchronous ECG
      channel is proposed in this paper. Considering the properties of wavelet filters
      and the relationship between wavelet basis and characteristics of ECG artifacts,
      the concepts for selecting a suitable wavelet basis and scales used in the
      process are developed. The analysis via the selected basis is without suffering
      time shift for decomposition and detection/elimination procedures after wavelet
      transformation. The detection rates, above 97.5% for MIT/BIH and NTUH recordings,
      show a pretty good performance in ECG artifact detection and elimination.

PMID- 17517387
TI  - Effects of trehalose co-incubation on in vitro matured prepubertal ovine oocyte
      vitrification.
AB  - Our aim was to evaluate if loading prepubertal ovine oocyte with trehalose would
      impact on their further developmental potential in vitro and if it would improve
      their survival to vitrification procedures. COCs matured in vitro with (TRH) or
      without (CTR) 100mM trehalose were tested for developmental potential after in
      vitro fertilization and culture. Trehalose uptake was measured by the antrone
      spectrophotometric assay. No differences were recorded between the two
      experimental groups in fertilization rates (91.1 CTR vs 92.5% TRH), cleavage
      rates calculated on fertilized oocytes (96.1 CTR vs 95.4% TRH), first cleavage
      kinetic (56.1 CTR vs 51% TRH), and blastocyst rates (14.3 CTR vs 13.0% TRH).
      Anthrone assay revealed that in TRH group trehalose concentration/oocyte was
      2.6microM. MII oocytes were then vitrified using cryoloops in TCM 199 containing
      20% FCS, sucrose 0.5M, 16.5% Me(2)SO, 16.5% EG and plunged in LN(2). After
      warming, oocytes from TRH and CTR groups were tested for membrane integrity using
      the propidium iodide (PI)/Hoechst differential staining, and for developmental
      ability after in vitro fertilization. Trehalose in maturation medium affected
      membrane resistance (P<0.01) to vitrification/warming but not fertilization and
      cleavage rates. The differential staining showed a lower number of PI positive
      cells in TRH group compared to CTR one (14.3 vs 24.7%, respectively).
      Fertilization rates and cleavage rates did not differ between the two groups
      (55.3 and 41% for TRH and 47.7 and 41.7% for CTR, respectively). In conclusion
      trehalose in maturation medium stabilizes cell membranes during
      vitrification/warming of prepubertal ovine oocytes but does not affect
      fertilization and cleavage rates after warming.

PMID- 17517388
TI  - Mercury speciation and emissions from coal combustion in Guiyang, Southwest
      China.
AB  - Although China has been regarded as one of the largest anthropogenic mercury
      emission source with coal combustion, so far the actual measurements of Hg
      species and Hg emissions from the combustion and the capture of Hg in Chinese
      emission control devices were very limited. Aiming at Hg mercury species
      measurements in Guiyang, the capital city of Guizhou province in Southwest China,
      we studied flue gases of medium-to-small-sized industrial steam coal-firing
      boiler (10-30 t/h) with no control devices, medium-to-small-sized industrial
      steam coal-firing boiler with WFGD and large-scale coal combustion with ESPs
      using Ontario Hytro method. We obtained mercury emission factors of the three
      representative coal combustion and estimated mercury emissions in Guiyang in
      2003, as well as the whole province from 1986 to 2002. Coal combustion in Guiyang
      emitted 1898 kg mercury to the atmosphere, of which 36% Hg is released from power
      plants, 41% from industrial coal combustion, and 23% from domestic users, and 267
      kg is Hg(p), 813 kg is Hg(2+) and 817 kg is Hg0. Mercury emission in Guizhou
      province increased sharply from 5.8 t in 1986 to 16.4 t in 2002. With the
      implementation of national economic strategy of China's Western Development, the
      annual mercury emission from coal combustion in the province is estimated to be
      about 32 t in 2015.

PMID- 17517389
TI  - Attic dust and human blood samples collected near a former wood treatment
      facility.
AB  - A wood treatment facility operating in southern Alabama released dioxins and
      other hazardous substances into the surrounding community over a period of
      approximately 35 years. The facility used a variety of chemical insecticides
      including pentachlorophenol (PCP), chromated copper arsenate (CCA), and creosote
      (which contains polycyclic aromatic hydrocarbons (PAHs)) to treat wood. The
      health risks associated with the released contaminants are numerous and
      significant. To evaluate the historic exposure to the contaminants from the
      facility, blood samples and health surveys were collected from 21 current and
      past residents of the adjacent, isolated community and analyzed for
      concentrations of polychlorinated dibenzo-p-dioxins (dioxins) and polychlorinated
      dibenzofurans (furans). In addition, attic dust sampling was performed in 11
      buildings located within a 1-mile radius of the former wood treatment facility.
      The average total dioxin toxic equivalent (TEQ) concentration in the residents'
      blood samples was 36.6 pg/g lipids. In the attic dust, the average total dioxin
      TEQ concentration, benzo[a]pyrene (PAH) TEQ concentration, and arsenic
      concentration were 145 ng/kg, 0.98 and 29.8 mg/kg, respectively. The
      concentrations of dioxins measured in the blood samples exceed the 90th
      percentile total dioxin levels found in the general US adult population.
      Concentrations of dioxin, arsenic, and PAHs found in the attic samples exceeded
      the US Environmental Protection Agency (USEPA) Region 4 soil exposure cancer risk
      preliminary remediation goal (PRG) values. These findings indicate a very
      significant potential for related health effects in these communities.

PMID- 17517390
TI  - Trypanosoma rangeli: RAPD-PCR and LSSP-PCR analyses of isolates from southeast
      Brazil and Colombia and their relation with KPI minicircles.
AB  - This study presents the first genetic characterization of five Trypanosoma
      rangeli isolates from Minas Gerais, in the southeast of Brazil and their
      comparison with Colombian populations by minicircle classification, RAPD-PCR and
      LSSP-PCR analyses. Our results demonstrated a homogenous T. rangeli population
      circulating among Didelphis albiventris as reservoir host in Brazil while
      heterogeneous populations were found in different regions of Colombia. KP1(+)
      minicircles were found in 100% isolates from Brazil and in 36.4% of the Colombian
      samples, whereas the KP2 and KP3 minicircles were detected in both groups. RAPD
      PCR and LSSP-PCR profiles revealed a polymorphism within KP1(+) and KP1(-) T.
      rangeli populations and allowed the division of T. rangeli in two branches. The
      Brazilian KP1(+) isolates were more homogenous than the KP1(+) isolates from
      Colombia. The RAPD-PCR were entirely consistent with the distribution of KP1
      minicircles while those obtained by LSSP-PCR were associated in 88.9% and 71.4%
      with KP1(+) and KP1(-) populations, respectively.

PMID- 17517391
TI  - Use of a 44k oligoarray to explore the transcriptome of Schistosoma mansoni adult
      worms.
AB  - Recent advances in the study of Schistosoma mansoni genome and transcriptome have
      led to a better description of the S. mansoni gene complement. In this work, we
      report the design and use of a new S. mansoni 60-mer oligonucleotide microarray
      platform with approximately 44,000 probes, based on all publicly available cDNA
      sequence data for S. mansoni and Schistosoma japonicum. The large number of
      probes combined with the extensive sequence annotation available allowed a
      comprehensive approach, where most of the S. mansoni transcriptome is
      represented. Hybridization with adult worm RNA pointed to a set of genes
      transcriptionally active in this stage of the parasite's life cycle.
      Interestingly, a large proportion (43%) of genes for which transcription was
      detected in adults is comprised of "no match" genes, i.e. S. mansoni genes with
      unknown function and no identifiable orthologs in GenBank. Moreover, detection of
      bi-directional transcription for 7% of the active "no match" genes in adults
      leads us to hypothesize a widespread production of antisense RNA in S. mansoni,
      with possible regulatory roles.

PMID- 17517392
TI  - Outgrowing endothelial progenitor-derived cells display high sensitivity to
      angiogenesis modulators and delayed senescence.
AB  - Outgrowing endothelial progenitor-derived cells (EPDCs) originate from a novel
      hierarchy of endothelial progenitor cells. In this study, EPDCs isolated from
      human cord blood were examined for phenotype and functional features upon aging.
      Young or aged EPDCs were similar to human umbilical vein endothelial cells
      (HUVECs), in exhibiting typical endothelial phenotypes. However, EPDCs were more
      sensitive to angiogenesis inducers or inhibitors in proliferation and migration.
      In addition, EPDCs underwent senescence markedly slowly with sustained
      endothelial NO synthase expression and activation, and their ability to undergo
      capillary morphogenesis was retained throughout longterm culture. Thus, these
      results suggest that a homogenous population of EPDCs derived from clonogenic
      expansion may provide an effective vasculogenesis tool.

PMID- 17517393
TI  - Synthesis of globopentaose using a novel beta1,3-galactosyltransferase activity
      of the Haemophilus influenzae beta1,3-N-acetylgalactosaminyltransferase LgtD.
AB  - We have previously described a bacterial system for the conversion of
      globotriaose (Gb3) into globotetraose (Gb4) by a metabolically engineered
      Escherichia coli strain expressing the Haemophilus influenzae lgtD gene encoding
      beta1,3-N-acetylgalactosaminyltransferase [Antoine, T., Bosso, C., Heyraud, A.
      Samain, E. (2005) Large scale in vivo synthesis of globotriose and globotetraose
      by high cell density culture of metabolically engineered Escherichia coli.
      Biochimie 87, 197-203]. Here, we found that LgtD has an additional beta1,3
      galactosyltransferase activity which allows our bacterial system to be extended
      to the synthesis of the carbohydrate portion of globopentaosylceramide (Galbeta
      3GalNAcbeta-3Galalpha-4Galbeta-4Glc) which reacts with the monoclonal antibody
      defining the stage-specific embryonic antigen-3. In vitro assays confirmed that
      LgtD had both beta1,3-GalT and beta1,3-GalNAcT activities and showed that
      differences in the affinity for Gb3 and Gb4 explain the specific and exclusive
      formation of globopentaose.

PMID- 17517394
TI  - Mutation C11994T in the mitochondrial ND4 gene is not a cause of low sperm
      motility in Portugal.
AB  - It has recently been suggested that a hitherto unobserved mutation, C11994T,
      causes oligoasthenozoospermia in men from India but at the same time does not
      affect systems other than the motility of the sperm. There are good reasons to
      question this proposition, in view of the worldwide mtDNA database and the Indian
      record in particular. We have further analyzed the oligoasthenozoospermic samples
      from a previous systematic study of infertile Portuguese men and found no
      instance of C11994T.

PMID- 17517395
TI  - Clomiphene citrate-induced follicular development in the presence of an ovarian
      ectopic pregnancy.
AB  - OBJECTIVE: To describe a case of a patient who had multiple follicular growth in
      the presence of an undiagnosed ectopic pregnancy (EP). DESIGN: Case report.
      SETTING: In vitro fertilization unit at a university hospital. PATIENT(S): A 34
      year-old patient with secondary infertility. INTERVENTION(S): Superovulation with
      clomiphene citrate (CC) and IUI. MAIN OUTCOME MEASURE(S): Follicular development
      with CC stimulation documented by transvaginal ultrasound and beta-hCG levels.
      RESULT(S): Two co-dominant follicles were observed with mean diameters of 22 mm
      and 24 mm. The patient had unexpectedly high levels of beta-hCG at the time of
      missed menses and was subsequently diagnosed with an ovarian EP. CONCLUSION(S):
      Multiple follicular growths can occur in response to CC in spite of the presence
      of an ovarian EP.

PMID- 17517396
TI  - Patient-friendly IVF: how should it be defined?
AB  - "Patient-friendly" IVF must be associated with a healthy newborn achieved in a
      safe, cost-effective, and timely manner. Patients are best served when physicians
      provide honest appraisal of treatment techniques and outcomes using the evidence
      available from scientific study.

PMID- 17517397
TI  - Mullerian-inhibiting substance inhibits cytochrome P450 aromatase activity in
      human granulosa lutein cell culture.
AB  - OBJECTIVE: To investigate the effects of Mullerian-inhibiting substance (MIS) on
      cytochrome P450 aromatase (CYP19) gene expression in cultured human granulosa
      lutein cells (GLC). DESIGN: In vitro primary cell culture study. SETTING:
      Academic research laboratory and hospital-based fertility center. PATIENT(S):
      Eight normo-ovulatory patients undergoing IVF procedures due to male factor or
      tubal infertility. INTERVENTION(S): Serum and follicular fluid (FF) collected and
      stored at -80 degrees C until assayed. Granulosa lutein cells were harvested from
      follicular aspirates obtained during oocyte retrieval and cultured for 7 days
      with media in the presence or absence of MIS (10 ng/mL) or FSH 0.2 IU/mL. MAIN
      OUTCOME MEASURE(S): Serum and FF levels of E2 and MIS, and E2 production by GLC
      in culture. Levels of CYP19 mRNA in cultured GLC were determined by quantitative
      polymerase chain reaction (PCR) and CYP19 protein by Western blot. Statistical
      comparison used ANOVA and post hoc Tukey tests. RESULT(S): Follicle-stimulating
      hormone significantly increased E2 production in cultured GLC compared with
      control. The increase in E2 production is associated with higher levels of CYP19
      mRNA and protein in GLC. The presence of MIS significantly inhibited FSH-induced
      E2 production, with concomitant reduction in CYP19mRNA and protein levels.
      CONCLUSION(S): Mullerian-inhibiting substance inhibits FSH augmentation of CYP19
      enzyme activity and CYP19 gene expression in GLC. These findings may help to
      explain the association of high MIS levels and low FF E2 levels reported in women
      with polycystic ovary syndrome (PCOS).

PMID- 17517398
TI  - Does sphingosine-1-phosphate have a protective effect on cyclophosphamide- and
      irradiation-induced ovarian damage in the rat model?
AB  - The aim of this study was to assess the possible protective effect of sphingosine
      1-phosphate (S1P), a polar sphingoid metabolite that seemingly promotes cell
      survival, on cytotoxin- and irradiation-induced ovarian injury in the rat model.
      Administration of S1P into ovarian bursa before whole-body irradiation led to
      decreased percentage of apoptotic cells, mostly in primordial follicles; however,
      S1P was not effective against apoptosis in rats that were given intraperitoneal
      cyclophosphamide.

PMID- 17517399
TI  - Short-term soybean intake and its effect on steroid sex hormones and cognitive
      abilities.
AB  - OBJECTIVE: To observe the effects of short-term soybean consumption on cognitive
      spatial abilities and changes in sex endocrine net in both genders. DESIGN: Short
      term prospective intervention study. SETTING: Academic medical center.
      PATIENT(S): Fifty-four healthy females and 32 healthy males (18 - 25 y of age).
      INTERVENTION(S): Volunteers were asked to eat 2 g/kg per day of soybeans during 1
      week. Saliva and plasma samples were taken, and psychometric tests were performed
      on the 1st (before soybean intake), 7th (after soybean intake), and 14th days
      (after washout period) of the study. MAIN OUTCOME MEASURE(S): Salivary T and
      plasma E(2) were measured. Mental rotation (MR) and spatial visualization (SV)
      tests were performed on the days of sampling. RESULT(S): Soybean intake did not
      change salivary T and plasma E(2) levels in men. During the washout period, both
      parameters have shown a tendency to rise. The effect of soybean intake on
      hormonal parameters in men was, however, dependent on the basal T levels. In
      women, salivary T as well as plasma E(2) levels showed a tendency toward a
      decline after soybean intake (the decrease in E(2) was statistically significant)
      and to increase back toward basal levels during the washout period. Both males
      and females statistically significantly improved in MR and SV after soybean
      intake. During the washout period, both genders further improved their results in
      MR but not in SV. CONCLUSION(S): Short-term soybean consumption alters the
      concentrations of salivary T and plasma E(2) in both men and women. Spatial
      abilities appear to be improved by short-term soybean intake, but the exact
      mechanisms require further study.

PMID- 17517400
TI  - Relationship and parenthood in IVF couples with twin and singleton pregnancies
      compared with spontaneous singleton primiparous couples--a prospective 5-year
      follow-up study.
AB  - OBJECTIVE: To analyze relationship and parenthood in IVF twin couples, IVF
      singleton couples, and spontaneously pregnant primiparous couples. SETTING:
      Southeast region of Sweden. DESIGN: Prospective case-control study. PATIENT(S):
      In total, 24 women and men who became pregnant with twins, consecutively, and
      expected their first child in 1997-98 were studied. A control IVF group of 94
      singleton primiparous IVF couples were used. A group of spontaneous primiparous
      pregnant women were selected out of the total pregnant population as a control
      group. MAIN OUTCOME MEASURE(S): Relationship and parenthood measured by
      questionnaires and interviews. RESULT(S): The IVF singleton couples were most
      stable in their relationship during the whole study period, and the IVF twin
      parents also seemed more stable and satisfied compared with the control group of
      spontaneous conception couples. In the control group, 88% had a second child
      during the study period. In the singleton IVF group the corresponding number was
      9%, and none of the twin parents had another child during the study period.
      CONCLUSION(S): We conclude that the stresses associated with IVF treatment and
      becoming first-time parents of twins did not have a negative impact on the
      couples' appreciation of their relationship and parenthood as stated by both men
      and women.

PMID- 17517401
TI  - Repeated successful induction of fertility after replacing hydrocortisone with
      dexamethasone in a patient with congenital adrenal hyperplasia and testicular
      adrenal rest tumors.
AB  - OBJECTIVE: To report repeated successful induction of fertility in an adult male
      patient with congenital adrenal hyperplasia (CAH) and testicular adrenal rest
      tumors (TART). DESIGN: Case report. SETTING: Radboud University Nijmegen Medical
      Centre. PATIENT(S): A 23-year-old male CAH patient with bilateral TART and
      azoospermia. INTERVENTION(S): Changing glucocorticoid medication from 30 mg of
      hydrocortisone to 0.75 mg of dexamethasone (DXM) daily. MAIN OUTCOME MEASURE(S):
      Improved semen analysis. RESULT(S): With the use of ultrasound screening, TART
      were detected in the 23-year-old patient. The semen analysis showed azoospermia.
      In an attempt to decrease tumor size and improve testicular function, his
      glucocorticoid medication was changed from hydrocortisone to an equivalent dosage
      of DXM. The azoospermia was quickly reversed, and his partner conceived within 7
      months of stopping oral contraceptives. Due to his progressive weight gain and
      striae, his medication was changed back to hydrocortisone, and he again developed
      again azoospermia. Two years later, the patient started again with DXM at the
      same dosage. His sperm concentration increased with progressive weight gain.
      Seven months later his partner became pregnant for the second time; afterward,
      the DXM treatment was changed back to hydrocortisone. CONCLUSION(S): In male CAH
      patients with testicular adrenal rest tumors, infertility may be reversible by
      replacing hydrocortisone with short courses of an equivalent dosage of DXM.

PMID- 17517402
TI  - Aneuploidy study in sperm and preimplantation embryos from nonmosaic 47,XYY men.
AB  - OBJECTIVE: To determine gonosomal and autosomal aneuploidy rate in sperm and
      preimplantation embryos from nonmosaic 47,XYY males. DESIGN: Sperm and blastomere
      analysis by fluorescence in situ hybridization. SETTING: Fertility clinic,
      academic hospital. PATIENT(S): Two 47,XYY men undergoing preimplantation genetic
      diagnosis (PGD) and eight 46,XY males distributed in two control groups (fertile
      and infertile). INTERVENTION(S): Sperm-sample collection for fluorescence in situ
      hybridization and PGD. MAIN OUTCOME MEASURE(S): Aneuploidy frequencies for
      chromosomes X, Y, 13, 16, 18, 21, and 22 in sperm and embryos. RESULT(S):
      Patients with 47,XYY presented global sperm gonosomal and autosomal aneuploidy
      frequency of 37.23%-37.80%, with XY disomy being the most frequent abnormality
      (16.70%-19.01%). This aneuploidy rate was statistically significantly different
      from that found in both 46,XY infertile controls (1.07%) and 46,XY fertile
      controls (1.04%). In total, 47 preimplantation embryos were analyzed, of which 32
      were classified as normal (68%) and 15 as aneuploid (32%). Among the abnormal
      embryos, 9 presented gonosomal abnormalities, and 6, autosomal abnormalities.
      CONCLUSION(S): High rate of gonosomal and autosomal aneuploidy was observed in
      sperm and preimplantation embryos from nonmosaic 47,XYY males. The offspring of
      this category of patients may be at higher risk of chromosomal abnormalities, and
      therefore PGD can be suggested to these patients.

PMID- 17517403
TI  - In vitro maturation of germinal vesicle oocytes recovered after premature
      luteinizing hormone surge: description of a novel approach to fertility
      preservation.
AB  - OBJECTIVE: To report a novel approach to fertility preservation by in vitro
      maturation and embryo cryopreservation after LH surge and ovulation. DESIGN: Case
      report. SETTING: Two university-based reproductive endocrinology clinics.
      PATIENT(S): Forty-year-old woman with breast cancer seeking fertility
      preservation before chemotherapy. INTERVENTION(S): The plan was ovarian
      stimulation and retrieval of mature oocytes, followed by IVF; however, premature
      LH surge and ovulation occurred before oocyte retrieval. Because no mature oocyte
      was recovered, follicles <10 mm in diameter were also aspirated. MAIN OUTCOME
      MEASURE(S): Recovery of immature oocytes after ovulation, in vitro maturation of
      these oocytes, and fertilization and vitrification of generated embryos.
      RESULT(S): Four immature oocytes were recovered, and two matured in vitro. After
      fertilization with intracytoplasmic sperm injection, embryos progressed to the
      four-cell stage on day 2 and were vitrified for future use. CONCLUSION(S): This
      case illustrates that under time constraints, immature oocytes can be recovered
      after ovulation and used to generate embryos for fertility preservation.

PMID- 17517404
TI  - Single tubule biopsy: a new objective microsurgical advancement for testicular
      sperm retrieval in patients with nonobstructive azoospermia.
AB  - OBJECTIVE: The aim of this study was to measure the diameter of seminiferous
      tubules (ST) during microdissection testicular sperm extraction (TESE) using a
      micrometer fixed to one of the eyepieces of the operating microscope to find a
      correlation between the extracted ST diameter and TESE outcome. DESIGN: A
      prospective comparative study. SETTING: Adam International Andrology and
      Infertility Clinic, Giza, Egypt. PATIENT(S): Two hundred sixty-four patients with
      nonobstructive azoospermia (NOA) were included. INTERVENTION(S): Patients
      underwent TESE using the open surgical technique. The STs were measured using the
      micrometer, and the tubule with the largest diameter was excised and freshly
      examined under an inverted microscope. If no spermatozoa were found, another
      sample was taken from the second most dilated tubule area and then at random
      until sperm were found or a maximum six samples were harvested. If no spermatozoa
      were detected, the contralateral testis was operated upon. MAIN OUTCOME
      MEASURE(S): The TESE outcome in relation to ST diameter. RESULT(S): The total
      sperm recovery rate was 105 out of 264 (39.8%). When ST measured >or=300 microm
      the sperm retrieval rate was 16 out of 19 (84.2%). When ST diameter was <300
      microm, the sperm retrieval rate was 36.3% (89 out of 245). CONCLUSION(S): During
      microdissection TESE, the best cutoff level of the ST diameter for harvesting
      testicular spermatoza is 110 microm with sensitivity 86.0% and specificity 74.4%
      (AUC 0.653, 95% confidence interval 0.608-0.663). When ST diameter is 300 microm
      or more a single tubule biopsy is usually sufficient to harvest enough testicular
      spermatozoa for intracytoplasmic sperm injection or sperm freezing with minimal
      tissue excision.

PMID- 17517405
TI  - Role of saline infusion sonography in uterine evaluation before frozen embryo
      transfer cycle.
AB  - OBJECTIVE: To determine the role of saline infusion sonography (SIS) in uterine
      evaluation before a frozen embryo transfer (FET) cycle. DESIGN: Retrospective
      cohort analysis. SETTING: University hospital. PATIENT(S): Thirty-six patients
      who had uterine evaluation by SIS before FET cycle. INTERVENTION(S): The SIS was
      performed in the follicular phase of the menstrual cycle before the actual FET
      cycle. MAIN OUTCOME MEASURE(S): The SIS findings, clinical pregnancy rate (PR),
      ongoing PR, and correlation between positive SIS findings with and without
      subsequent treatment and pregnancy outcome. RESULT(S): Positive SIS findings were
      found in 11/36 patients (30.5%), which included uterine septum (9.0%),
      endometrial polyp (45.4%), intramural fibroid with normal cavity (9.0%), cystic
      endometrial changes (9.0%), cervical stenosis (18.1%), and calcification with
      normal cavity (9.0%). The overall clinical PR in all groups was 51.4%, with an
      ongoing PR of 45.7%. Patients with positive SIS finding who underwent subsequent
      hysteroscopic correction (7/11) had a clinical PR of 85.7% as compared to 54.1%
      in patients with normal uterine cavity (24/35). Patients with positive SIS
      findings and no operative hysteroscopy (4/11) had a clinical PR of 50% and
      pregnancy loss rate of 100%. CONCLUSION(S): Obtaining an SIS before the FET cycle
      can be helpful in the detection of uterine abnormalities. If time since uterine
      evaluation has been more than 1-2 years, performing an SIS is recommended as
      subsequent correction of the anomalies may improve FET outcome.

PMID- 17517406
TI  - Cryosurvival and spermatogenesis after allografting prepubertal mouse tissue:
      comparison of two cryopreservation protocols.
AB  - Although childhood cancer treatments are yielding higher survival rates,
      sterility remains one of the major side effects. For prepubertal boys there are
      currently no options to preserve fertility. Testicular tissue banking together
      with subsequent grafting may become a possible strategy in the future. In the
      present study, we compared two cryopreservation protocols using prepubertal
      murine testicular tissue. Fresh and cryopreserved testicular tissue was grafted
      subcutaneously on the back of immune-deficient mice for at least 3 months.
      Prepubertal murine tissue recovered well after cryopreservation with both
      ethylene glycol (EG) and dimethylsulfoxide (DMSO). While in fresh murine
      allografts, spermatozoa were observed in 23% of the tubules; in both the DMSO and
      the EG groups, 32% of the seminiferous tubules contained spermatozoa. However,
      with DMSO the structure of the seminiferous tubules was better preserved.

PMID- 17517407
TI  - Successful term pregnancy in a patient with Wegener's granulomatosis: case report
      and literature review.
AB  - OBJECTIVE: To present a case of successful term pregnancy in a patient with known
      Wegener's granulomatosis (WG). DESIGN: Case report. SETTING: University Hospital,
      Department of Obstetrics and Gynecology. PATIENT(S): A 22-year-old primigravida
      pregnant woman with a history of WG diagnosed 5 years before. INTERVENTION(S):
      The patient was treated with corticosteroids and azathioprine throughout
      pregnancy, and cyclophosphamide was added postpartum. MAIN OUTCOME MEASURE(S):
      The disease was in partial remission at the onset of pregnancy, but two relapses
      occurred, at 33 weeks' gestation and 15 days after delivery. A 3150-g healthy boy
      was delivered at 37 weeks' gestation. CONCLUSION(S): Pregnancy in patients with
      WG requires preconceptional planning, careful clinical management, and vigorous
      treatment of active disease. There are 36 cases of WG in pregnancy reported in
      the literature. Owing to this rarity, the management is individualized and the
      pregnancy outcome is variable. Antenatal management and therapeutic options are
      discussed and a short review of the literature is presented.

PMID- 17517408
TI  - Association of secondary sex ratio with smoking and parity.
AB  - OBJECTIVE: To assess the sex ratio in offspring of smoking and nonsmoking mothers
      in relationship to parity. DESIGN: Prospective study. SETTING: University
      hospital. PATIENT(S): The authors studied 2,108 term singleton neonates born
      between 1993 and 2002, 665 from smoking mothers and 1,443 from nonsmoking
      mothers. INTERVENTION(S): A prospective recording of maternal age, parity and
      smoking status, and gender of neonates delivered over a 10-year period. MAIN
      OUTCOME MEASURE(S): Secondary sex ratio in regard to maternal smoking and parity.
      RESULT(S): The offspring sex ratio in the total sample studied was 1.09; in the
      offspring of smoking and nonsmoking mothers, it was 1.26 and 1.03, respectively,
      a statistically significant difference. In the offspring of smoking women who had
      parity 1, 2, and >or=3, it was 1.47, 1.35, and 0.92, whereas in those of
      nonsmoking women, it was 1.04, 1.00, and 1.03, respectively (the differences of
      the parity 1 and 2 groups between the offspring of smoking and nonsmoking mothers
      were statistically significant). Logistic regression analysis showed that the
      possibility of a boy being delivered by a mother who smoked was significantly
      greater in primiparous women than in women who had parity >or=3, independent of
      the maternal age. Conversely, parity did not affect significantly the sex ratio
      in the offspring of nonsmoking women. CONCLUSION(S): The findings suggest that
      among women who smoked, significantly more male than female offspring are born
      from primiparous women, whereas women who had parity >or=3 gave birth to more
      female offspring; biparous women give birth to significantly more male offspring,
      but the offspring sex ratio declined with the number of cigarettes when the
      mothers smoked >or=10 cigarettes per day.

PMID- 17517409
TI  - Day 4 versus day 3 embryo transfer: a prospective study of clinical outcomes.
AB  - OBJECTIVE: To compare the clinical outcomes after day 4 or day 3 embryo transfers
      in controlled ovarian hyperstimulation-IVF/intracytoplasmic sperm injection
      (ICSI) cycles. DESIGN: Prospective randomized study. SETTING: Center for Human
      Reproduction, 'Genesis Athens' Clinic (private gynecological and surgical
      clinic), Athens, Greece. PATIENT(S): Three hundred fifty women with primary
      infertility and indication for IVF/ICSI treatment. Patients were randomly
      allocated to day 4 or day 3 embryo transfer. INTERVENTION(S): Controlled ovarian
      hyperstimulation, oocyte retrieval, IVF/ICSI, embryo transfer. MAIN OUTCOME
      MEASURE(S): Implantation rate; clinical, ongoing, and multiple pregnancy rates.
      RESULT(S): A trend toward higher clinical and ongoing pregnancy rates was noted
      after day 4 embryo transfers. Implantation and multiple pregnancy rates were
      comparable after day 4 or day 3 embryo transfers. CONCLUSION(S): The transfer of
      day 4 embryos in IVF/ICSI cycles may result in favorable implantation and
      pregnancy rates which are at least comparable to those after the transfer of day
      3 embryos.

PMID- 17517411
TI  - Immune function varies with reproductive stage and context in female and male
      tree lizards, Urosaurus ornatus.
AB  - Competition among physiological processes for limited resources often results in
      trade-offs. Key among these processes is reproduction and immune function, and
      optimizing both appears to be difficult. To test the hypothesis that the resource
      demands of reproduction compromise immune function, we measured rates of wound
      healing, an integrated measure of innate immunity, across different reproductive
      stages in female and male tree lizards (Urosaurus ornatus) in both the field and
      the laboratory. The hypothesis predicted that immune function would be lowest
      when resource demands of reproduction are highest, i.e., vitellogenic females and
      reproductive males. In the field, vitellogenic females had significantly slower
      healing rate than females in other reproductive stages. However, in the
      laboratory, vitellogenic females had a healing rate similar to that of other
      females. Conversely, males showed suppression of healing in the laboratory but
      not in the field during the reproductive season. The results of this study
      support a trade-off between reproduction and immune function, and suggest that
      reproduction is given priority. However, the results also indicate that this
      trade-off is not fixed in the reproductive process and that it may instead be
      dependent on the context, sex or resource balance of the individual.

PMID- 17517410
TI  - On the role of urocortin 1 in the non-preganglionic Edinger-Westphal nucleus in
      stress adaptation.
AB  - The discovery of novel members of the CRF neuropeptide family, urocortin 1
      (Ucn1), urocortin 2 and 3 has provided important insights into stress adaptation
      pathways, and predicted that stress adaptation involves more systems than the HPA
      axis alone. This mini-review aims to summarize our recent data and research by
      others indicating that an important role is played by Ucn1 in the non
      preganglionic Edinger-Westphal nucleus (npEW). These results point to an
      intriguing possibility that CRF/Ucn1 neuronal circuits comprise two separate, but
      functionally interrelated entities, which are coordinately regulated by acute
      stressors, but are inversely coupled during chronic stress. Such collaboration
      between the two systems would implicate a very important role of Ucn1 in
      adaptation to stress, and, as a consequence, in stress-related disorders like
      anxiety, major depression and use of drugs of abuse.

PMID- 17517412
TI  - A continuous analysis of multi-input, multi-output predictive control.
AB  - A continuous formulation and method of analysis is constructed for multi-input,
      multi-output (MIMO) predictive control and used to compare Dynamic Matrix Control
      (DMC) with Simplified Predictive Control (SPC). Approximate characteristic
      equations are derived for each of DMC and SPC and these are used to determine,
      and thus compare, the closed-loop control behaviour of these methods at times
      long compared with the sampling time. The MIMO control problem considered is the
      general case of control over two coupled zones of a first order, linear process
      where a single control move is simultaneously input into each zone and a single
      output or measurement, is made from within each zone. The analytical results are
      illustrated through MIMO control of the terminal composition of a binary
      distillation column. A practically important result is an analytic basis to
      understand previous experimental observations that, for a wide range of
      processes, SPC appears to be as capable as the more sophisticated DMC.
      Furthermore, it is also shown here that SPC is well-conditioned over its entire
      parameter range in contrast to DMC. This well-conditioned behaviour makes it
      especially suitable for remote applications where unknown, and variable timing of
      future moves may be a significant issue.

PMID- 17517413
TI  - Faecal soiling and gastrointestinal helminth infection in lambs.
AB  - The accumulation of faeces in the wool of the breech area (tail, perineum and
      anus) of lambs, known as faecal soiling, has been shown to be one of the major
      factors predisposing sheep to blowfly strike. However, the causes of faecal
      soiling of lambs in the UK are not clearly understood. Hence, in this
      investigation, the relationships between faecal soiling, gastrointestinal
      parasitic nematode infection and resultant diarrhoea were examined in a
      longitudinal study of 200 lambs at two farms in south-west England. Faecal egg
      counts, pasture worm burdens, faecal soiling and growth rates were recorded for
      individually tagged lambs over the summer of 2003. Grass growth and nutritional
      composition (protein and fibre) and weather data were also recorded over this
      period. Analysis using linear mixed models showed that faecal soiling was
      associated with higher strongyle-type egg counts, longer periods since worming,
      lower live-weights, female gender, lower faecal consistency and pasture quality.
      The data indicate that dag scoring, especially in mid- to late summer, could be
      used as a rapid, non-invasive technique for selecting animals, particularly
      lambs, with high faecal egg counts for selective drenching to reduce the
      incidence of anthelmintic resistance. Selective drenching of lambs with high dag
      scores would also be expected to aid in the control of blowfly strike.

PMID- 17517414
TI  - Active uptake of cyst nematode parasitism proteins into the plant cell nucleus.
AB  - Cyst nematodes produce parasitism proteins that contain putative nuclear
      localisation signals (NLSs) and, therefore, are predicted to be imported into the
      nucleus of the host plant cell. The in planta localisation patterns of eight
      soybean cyst nematode (Heterodera glycines) parasitism proteins with putative
      NLSs were determined by producing these proteins as translational fusions with
      the GFP and GUS reporter proteins. Two parasitism proteins were found to be
      imported into the nuclei of onion epidermal cells as well as Arabidopsis
      protoplasts. One of these two parasitism proteins was further transported into
      the nucleoli. Mutations introduced into the NLS domains of these two proteins
      abolished nuclear import and caused a cytoplasmic accumulation. Furthermore, we
      observed active nuclear uptake for three additional parasitism proteins, however,
      only when these proteins were synthesised as truncated forms. Two of these
      proteins were further transported into nucleoli. We hypothesise that nuclear
      uptake and nucleolar localisation are important mechanisms for H. glycines to
      modulate the nuclear biology of parasitised cells of its host plant.

PMID- 17517416
TI  - Opening angle and residual strain in a three-layered model of pig oesophagus.
AB  - Studies of various biological tissues have shown that residual strains are
      important for tissue function. Since a force balance exists in whole wall
      thickness specimens cut radially, it is evident that layer separation is an
      important procedure in the understanding of the meaning of residual stresses and
      strains. The present study investigated the zero-stress state and residual strain
      distribution in a three-layer model of the pig oesophagus. The middle part of the
      oesophagus was obtained from six slaughterhouse pigs. Four 3-mm-wide rings were
      serially cut from each oesophagus. Two of them were used for separating the wall
      into mucosa-submucosa, inner and outer muscle layers. The remaining two rings
      were kept as intact rings. The inner and outer circumferences and wall thickness
      of different layers in intact and separated rings were measured from the digital
      images in the no-load state and zero-stress state. The opening angle was measured
      and the residual strain at the inner and outer surface of different layers and
      the intact wall were computed. Compared with intact sectors (62.8+/-9.8 degrees
      ), the opening angles were smaller in the inner muscle sectors (37.2+/-11.4
      degrees , P<0.01), whereas the opening angles of mucosa-submucosa (63.9+/-6.8
      degrees ) and outer muscle sectors (63.9+/-6.8 degrees ) did not differ (P>0.1).
      Referenced to the zero-stress state of the intact sectors, the inner and outer
      residual strains of the intact rings was -0.128+/-0.043 and outer residual strain
      was 0.308+/-0.032. Referenced to the "true" zero-stress state of separated three
      layered sectors, the inner residual strain of intact rings were -0.223+/-0.021
      (P<0.01) and 0.071+/-0.022 (P<0.01). Referenced to the "true" zero-stress state,
      the residual strain distribution of different layers in intact rings was shown
      that the inner surface residual strain was negative at mucosa-submucosa and inner
      muscle layers and was positive at outer muscle layer, whereas the outer surface
      residual strain was negative at the mucosa-submucosa layer and positive at the
      inner and outer muscle layers. For the separated different layered rings, the
      inner residual strain was negative and outer residual strain was positive;
      however, the absolute values did not differ (P>0.1). In conclusion, it is
      possible to microsurgically separate the oesophagus into three layers, i.e.,
      mucosa-submucosa, inner muscle and outer muscle layers, the residual strain
      differ between the layers, and the residual strain distribution was more uniform
      after the layers were separated.

PMID- 17517415
TI  - Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies.
AB  - A thorough understanding of the transmission mechanism of any infectious agent is
      crucial to implementing an effective intervention strategy. Here, our current
      understanding of the mechanisms that Leishmania parasites use to ensure their
      transmission from sand fly vectors by bite is reviewed. The most important
      mechanism is the creation of a "blocked fly" resulting from the secretion of
      promastigote secretory gel (PSG) by the parasites in the anterior midgut. This
      forces the sand fly to regurgitate PSG before it can bloodfeed, thereby
      depositing both PSG and infective metacyclic promastigotes in the skin of a
      mammalian host. Other possible factors in transmission are considered: damage to
      the stomodeal valve; occurrence of parasites in the salivary glands; and
      excretion of parasites from the anus of infected sand flies. Differences in the
      transmission mechanisms employed by parasites in the three subgenera, Leishmania,
      Viannia and Sauroleishmania are also addressed.

PMID- 17517417
TI  - In-situ graft-polymerization preparation of cation-exchange supermacroporous
      cryogel with sulfo groups in glass columns.
AB  - Graft polymerization of monomer chains with expected functional groups onto the
      matrix pore surfaces by initiator is an effective approach for introducing ion
      exchange groups to cryogel matrix to get anion- or cation-exchange
      supermacroporous cryogels. In this work, a novel cation-exchange cryogel with
      sulfo binding groups was prepared by grafting of 2-acrylamido-2-methyl-1
      propanesulfonic acid (AMPSA) onto polyacrylamide-based cryogels in glass columns.
      The grafting polymerization was achieved in an in-situ manner which was performed
      by pumping the initiator and the reactive solution of graft monomer with sulfo
      binding groups directly through a cryogel bed pre-produced in a glass column
      under frozen condition. The axial liquid dispersion characteristics within the
      monolithic cryogel beds before and after the in-situ polymerization were compared
      by measuring residence time distributions (RTDs) at various liquid flow rates
      using tracer pulse-response method. Microstructure morphology of pores within
      cryogels was analyzed by scanning electron microscopy (SEM). Chromatography of
      lysozyme was carried out to reveal the protein breakthrough and elution
      characteristics in the obtained cryogel beds.

PMID- 17517418
TI  - Capillary electrophoresis tandem mass spectrometry of bromine-containing charged
      derivatives of peptides.
AB  - Novel bromine-containing positively charged labels 5-bromo-1-ethyl-thiazolium
      (BET+) and 5-bromo-1-ethyl-pyridinium (BEP+) ions were studied for improving the
      interpretation of MS/MS spectra of peptides. 2,5-Dibromo-1-ethyl-thiazolium
      tetrafluoroborate (DBET) reacts in the order: epsilon->>alpha-amino
      group>>hydroxyl group of Tyr while 2,5-dibromo-1-ethyl-pyridinium
      tetrafluoroborate (DBEP) reacts preferably with thiol group of Cys>>hydroxyl
      group of Tyr. In this study a simple and fast CE/MS/MS method is presented for
      investigating the labeling reaction with these new reagents, where the difference
      in migration times of labeled and unlabeled peptides also gives us information
      about the position of labeling. These bromine-containing reagents simplify the
      MS/MS spectra of peptides: the charge of the derivatives increases the intensity
      of the corresponding ions, thus enhancing the sensitivity of the detection and
      the characteristic distribution of the bromine isotope (the 79Br and 81Br ratio
      is nearly one) facilitating the recognition. By eliminating the non-doubled
      peaks, clear and easily interpretable MS/MS spectra can be produced that contain
      only the labeled fragments.

PMID- 17517419
TI  - Analysis of triacylglycerols on porous graphitic carbon by high temperature
      liquid chromatography.
AB  - The retention behaviour of several triacylglycerols (TAGs) and fats on Hypercarb,
      a porous graphitic carbon column (PGC), was investigated in liquid chromatography
      (LC) under isocratic elution mode with an evaporative light scattering detector
      (ELSD). Mixtures of chloroform/isopropanol were selected as mobile phase for a
      suitable retention time to study the influence of temperature. The retention was
      different between PGC and non-aqueous reversed phase liquid chromatography (NARP
      LC) on octadecyl phase. The retention of TAGs was investigated in the interval 30
      70 degrees C. Retention was greatly affected by temperature: it decreases as the
      column temperature increases. Selectivity of TAGs was also slightly influenced by
      the temperature. Moreover, this chromatographic method is compatible with a mass
      spectrometer (MS) detector by using atmospheric pressure chemical ionisation
      (APCI): same fingerprints of cocoa butter and shea butter were obtained with LC
      ELSD and LC-APCI-MS. These preliminary results showed that the PGC column could
      be suitable to separate quickly triacylglycerols in high temperature conditions
      coupled with ELSD or MS detector.

PMID- 17517420
TI  - Determination of volatile phenols in red wines by dispersive liquid-liquid
      microextraction and gas chromatography-mass spectrometry detection.
AB  - A new method was developed for analysing 4-ethylguaiacol and 4-ethylphenol in the
      aroma of red wines using dispersive liquid-liquid microextraction (DLLME) coupled
      with gas chromatography-mass spectrometry detection (GC-MS). Parameters such as
      extraction solvent, sample volume and disperser solvent were studied and
      optimised to obtain the best extraction results with the minimum interference
      from other substances, thus giving clean chromatograms. The response linearity
      was studied in the usual concentration ranges of analytes in wines (50-1500
      microg/L). Repeatability and reproducibility of this method were lower than 5%
      for both volatile phenols. Limits of detection and limits of quantification were
      also determined, and the values found were 28 and 95 microg/L for 4-ethylguaiacol
      and 44 and 147 microg/L for 4-ethylphenol, respectively. This new method has been
      used for the determination of the volatile phenols concentration in different
      samples of Tannat wine affected by Brettanomyces contamination.

PMID- 17517421
TI  - Simultaneous analysis of four stereoisomers of anti-benzo[a]pyrene diol epoxide
      deoxyguanosine adducts in short oligodeoxynucleotides using reversed-phase high
      performance liquid chromatography.
AB  - anti-Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (anti-BPDE), a reactive
      metabolite of the environmental carcinogen benzo[a]pyrene, predominantly binds to
      deoxyguanine in DNA and forms four stereoisomeric adducts. Here we developed an
      improved method for simultaneous analysis and purification of four stereoisomeric
      adducts in short oligonucleotides using reversed-phase high-performance liquid
      chromatography, providing a selection strategy of stationary phase for analysis
      and separation of polyaromatic hydrocarbon-DNA adducts. This work demonstrates
      that secondary retention of oligonucleotides on C18 stationary phases induced by
      exposed silanol heavily affects the separation of four stereoisomeric adducts on
      C18 stationary phases, and the silicone polymer monolayer coating for completely
      capping exposed silica or silanol greatly reduces such secondary retention,
      thereby displaying a much better resolution of the four stereoisomeric adducts.
      We further demonstrate that aromatic group (phenyl)-based stationary phase can
      significantly improve stereoisomeric separation of four anti-BPDE-deoxyguanosine
      (dG) adducts in short oligonucleotides over nonaromatic C18 stationary phase due
      to enhancement of the selective interaction with aromatic anti-BPDE moiety in
      oligonucleotides. The developed method was also used for purification and
      preparation of anti-BPDE-oligonucleotide adducts.

PMID- 17517422
TI  - CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a
      selective blocker of L-type calcium channels in mammalian neurons.
AB  - The inhibitor cystine-knot motif identified in the structure of CSTX-1 from
      Cupiennius salei venom suggests that this toxin may act as a blocker of ion
      channels. Whole-cell patch-clamp experiments performed on cockroach neurons
      revealed that CSTX-1 produced a slow voltage-independent block of both mid/low-
      (M-LVA) and high-voltage-activated (HVA) insect Ca(v) channels. Since C. salei
      venom affects both insect as well as rodent species, we investigated whether
      Ca(v) channel currents of rat neurons are also inhibited by CSTX-1. CSTX-1
      blocked rat neuronal L-type, but no other types of HVA Ca(v) channels, and failed
      to modulate LVA Ca(v) channel currents. Using neuroendocrine GH3 and GH4 cells,
      CSTX-1 produced a rapid voltage-independent block of L-type Ca(v) channel
      currents. The concentration-response curve was biphasic in GH4 neurons and the
      subnanomolar IC(50) values were at least 1000-fold lower than in GH3 cells. L
      type Ca(v) channel currents of skeletal muscle myoballs and other voltage-gated
      ion currents of rat neurons, such as I(Na(v)) or I(K(v)) were not affected by
      CSTX-1. The high potency and selectivity of CSTX-1 for a subset of L-type
      channels in mammalian neurons may enable the toxin to be used as a molecular tool
      for the investigation of this family of Ca(v) channels.

PMID- 17517423
TI  - Functional evidence for GABA as modulator of the contractility of the
      longitudinal muscle in mouse duodenum: role of GABA(A) and GABA(C) receptors.
AB  - We investigated, in vitro, the effects of gamma-aminobutyric acid (GABA) on the
      spontaneous mechanical activity of the longitudinal smooth muscle in mouse
      duodenum. GABA induced an excitatory effect, consisting in an increase in the
      basal tone, which was antagonized by the GABA(A)-receptor antagonist,
      bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid
      hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by
      phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist,
      induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX),
      hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C)
      receptor agonist, induced an inhibitory effect, consisting in the reduction of
      the amplitude of the spontaneous contractions and muscular relaxation, which was
      antagonised by TPMPA, GABA(C)-receptor antagonist, TTX or N(omega)-nitro-l
      arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor, but not
      affected by hexamethonium. In conclusion, our study indicates that GABA is a
      modulator of mechanical activity of longitudinal muscle in mouse duodenum. GABA
      may act through neuronal presynaptic receptors, namely GABA(A) receptors, leading
      to the release of ACh from excitatory cholinergic neurons, and GABA(C) receptors
      increasing the release of NO from non-adrenergic, non-cholinergic inhibitory
      neurons.

PMID- 17517424
TI  - Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from
      MPTP toxicity.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is closely involved in neuronal
      apoptosis and pathogenesis of many neurodegenerative diseases, such as
      Alzheimer's disease. However, whether GSK-3beta mediates apoptosis of
      dopaminergic neurons in Parkinson's disease remains elusive. In this study, using
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism models,
      we investigated whether MPTP induces apoptosis of dopaminergic neurons through a
      GSK-3beta-dependent pathway. MPTP caused a rapid activation of GSK-3beta,
      evidenced by the decrease in level of phospho-Ser9 of GSK-3beta and the increase
      in level of phospho-Ser396 of tau, a known GSK-3beta substrate. Blockage of GSK
      3beta activity by its two specific inhibitors, indirubin-3'-oxime and AR-A014418,
      prevented dopaminergic neurons from MPTP-induced apoptosis. Additionally,
      inhibition of GSK-3beta activity restored the depletion of striatal dopamine and
      ameliorated behavioral impairments caused by MPTP. These results indicate that
      GSK-3beta is a critical intermediate of MPTP neurotoxicity, and inhibition of GSK
      3beta may provide a novel strategy to treat Parkinson's disease.

PMID- 17517425
TI  - Intact subliminal processing and delayed conscious access in multiple sclerosis.
AB  - Periventricular white matter damage affecting large bundles connecting distant
      cortical areas may constitute the main neuronal mechanism for the deficit of
      controlled information processing observed in patients with early multiple
      sclerosis (MS). Visual backward masking has been demonstrated to affect late
      stages of conscious perception involving long-range interactions between visual
      perceptual areas and higher level integrative cortices while leaving intact early
      feed-forward visual processing and even complex processing such as object
      recognition or semantic processing. We therefore hypothesized that patients with
      early MS would have an elevated masking threshold, because of an impairment of
      conscious perception whereas subliminal processing of masked stimuli would be
      preserved. Twenty-two patients with early MS and 22 normal controls performed two
      backward-masking experiments. We used Arabic digits as stimuli and varied quasi
      continuously the temporal interval with a subsequent mask, thus allowing us to
      progressively "unmask" the stimuli. We finely quantified the visibility of the
      masked stimuli using both objective and subjective measures, thus obtaining
      accurate estimates of the threshold duration for access to consciousness. We also
      studied the priming effect caused by the variably masked numbers on a comparison
      task performed on a subsequently presented and highly visible target number. The
      threshold for access to consciousness of masked stimuli was elevated in MS
      patients compared to controls, whereas non-conscious processing of these stimuli,
      as measured by priming, was preserved. These findings suggest that conscious
      access to masked stimuli depends on the integrity of large-scale cortical
      integrative processes, which involve long-distance white matter projections, and
      are impaired due to diffuse demyelinating injury in patients with early MS.

PMID- 17517427
TI  - First report of homoanatoxin-a and associated dog neurotoxicosis in New Zealand.
AB  - In November 2005, at least five dogs died rapidly after contact with water from
      the Hutt River (lower North Island, New Zealand). Necropsy performed 24h later on
      one of the dogs (a 20-month-old Labrador) revealed few findings of interest,
      except for copious amounts of froth in the respiratory tract down to the
      bifurcation of the trachea and large quantities of algal material in the dog's
      stomach. Low and relatively stable flows in the Hutt River during spring had
      resulted in the proliferation of benthic cyanobacteria that formed large
      black/brown mats along the river edge. Samples from the Labrador's stomach
      contents and cyanobacterial mats were analysed microscopically and screened using
      chemical and biochemical assays for cyanotoxins: anatoxin-a, homoanatoxin-a,
      cylindrospermopsins, saxitoxins and microcystins. Liquid chromatography-mass
      spectrometry (LC-MS) confirmed the presence of the neurotoxic cyanotoxins
      anatoxin-a and homoanatoxin-a and their degradation products, dihydro-anatoxin-a
      and dihydro-homoanatoxin-a. This is the first report of homoanatoxin-a and
      associated degradation product in New Zealand. Based on morphology, the causative
      species was identified as Phormidium sp. Subsequent phylogenetic analysis of 16S
      rRNA gene sequences demonstrated that the causative organism was most similar to
      Phormidium autumnale. Further investigations led to the detection of homoanatoxin
      a and anatoxin-a in cyanobacterial mats from four other rivers in the Wellington
      region (lower North Island, New Zealand). Access restrictions were placed on over
      60% of river catchments in the western Wellington region, severely affecting
      recreational users.

PMID- 17517426
TI  - Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from
      Pentaclethra macroloba.
AB  - We report here the antiproteolytic and antihemorrhagic properties of triterpenoid
      saponin inhibitors, named macrolobin-A and B, from Pentaclethra macroloba,
      against Bothrops snake venoms. The inhibitors were able to neutralize the
      hemorrhagic, fibrin(ogen)olytic, and proteolytic activities of class P-I and P
      III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms.
      Clotting and fibrinogenolytic activities induced by snake venoms and isolated
      thrombin-like enzymes were partially inhibited. Furthermore, the potential use of
      these inhibitors to complement antivenom therapy as an alternative treatment
      and/or used as molecular models for development of new therapeutical agents in
      the treatment of snake bite envenomations needs to be evaluated in future
      studies.

PMID- 17517428
TI  - Direct evidence for interaction between lead ions and kidney DNA from silver
      crucian carp.
AB  - A direct interaction of lead (Pb) with kidney DNA from silver crucian carp
      (Carassius auratus gibelio) has been systematically studied in vitro using multi
      techniques, including UV-vis absorption, extended X-ray absorption fine
      structure, vacuum ultraviolet circular dichroism spectral methods and gel
      electrophoresis. We find that Pb is bound with four oxygen or nitrogen atoms of
      DNA in its fresh shell at the distances of 2.64 A. Additionally, Pb may bind to
      the oxygen atom of nucleic acid or nitrogen atom of base pairs of DNA in that
      obvious changes in the secondary structure of DNA are found after Pb treatment.
      However, this direct interaction of Pb with DNA do not cause DNA cleavage in
      vitro.

PMID- 17517429
TI  - Violations of information structure: an electrophysiological study of answers to
      wh-questions.
AB  - This study investigates brain responses to violations of information structure in
      wh-question-answer pairs, with particular emphasis on violations of focus
      assignment in it-clefts (It was the queen that silenced the banker). Two types of
      ERP responses in answers to wh-questions were found. First, all words in the
      focus-marking (cleft) position elicited a large positivity (P3b) characteristic
      of sentence-final constituents, as did the final words of these sentences, which
      suggests that focused elements may trigger integration effects like those seen at
      sentence end. Second, the focusing of an inappropriate referent elicited a
      smaller, N400-like effect. The results show that comprehenders actively use
      structural focus cues and discourse-level restrictions during online sentence
      processing. These results, based on visual stimuli, were different from the brain
      response to auditory focus violations indicated by pitch-accent [Hruska, C.,
      Steinhauer, K., Alter, K., & Steube, A. (2000). ERP effects of sentence accents
      and violations of the information structure. In Poster presented at the 13th
      annual CUNY conference on human sentence processing, San Diego, CA.], but similar
      to brain responses to newly introduced discourse referents [Bornkessel, I.,
      Schlesewsky, M., & Friederici, A. (2003). Contextual information modulated
      initial processes of syntactic integration: the role of inter- versus
      intrasentential predictions. Journal of Experimental Psychology: Learning, Memory
      and Cognition, 29, 871-882.].

PMID- 17517430
TI  - The angiogenic potential of three-dimensional open porous synthetic matrix
      materials.
AB  - Angiogenesis is a complex multistage process involving multiple factors and
      numerous cells. The use of the Chorioallantoic Membrane (CAM) assay is well
      documented as a method to investigate angiogenesis. This technique is ideal for
      screening samples, but requires an objective analysis technique. The angiogenic
      response of vascular endothelial growth factor (VEGF) was used to confirm that
      computer-based image analysis was able to quantify angiogenesis. Image analysis
      was used on samples of increasing porosity of PLLA to determine the effect of
      pore size on angiogenesis. Another effect also noted was that of an inflammatory
      response co-incident with angiogenesis. The difference in pore size made a
      difference to both angiogenesis and inflammation. Real-time polymerase chain
      reaction (PCR) was used with primers for TNF-alpha to demonstrate and measure the
      presence of an inflammatory response.

PMID- 17517431
TI  - Neural probe design for reduced tissue encapsulation in CNS.
AB  - This study investigated relationships between a microscale neural probe's size
      and shape and its chronic reactive tissue response. Parylene-based probes were
      microfabricated with a thick shank (48 microm by 68 microm) and an integrated
      thin lateral platform (5 microm by 100 microm, either solid or one of three
      lattice sizes). Devices were implanted in rat cerebral cortex for 4 weeks before
      immunostaining for neurons, astrocytes, microglia, fibronectin, laminin, and
      neurofilament. While nonneuronal density (NND) generally increased and neuronal
      density decreased within 75 microm of a probe interface compared to unimplanted
      control regions, there were significant differential tissue responses within 25
      microm of the platform's lateral edge compared to the shank. The NND in this
      region of the lateral edge was less than one-third of the corresponding region of
      the shank (129% and 425% increase, respectively). Moreover, neuronal density
      around the platform lateral edge was about one-third higher than at the shank
      (0.70 and 0.52 relative to control, respectively). Also, microglia reactivity and
      extracellular protein deposition was reduced at the lateral edge. There were no
      significant differences among platform designs. These results suggest that neural
      probe geometry is an important parameter for reducing chronic tissue
      encapsulation.

PMID- 17517432
TI  - Increased bioavailability of TNF-alpha in African Americans during in vitro
      infection: predisposing evidence for immune imbalance.
AB  - OBJECTIVE: The objective of this study is to examine TNF-alpha and its soluble
      and membrane bound receptors in fetal membranes derived from blacks and whites in
      response to in vitro infectious stimulus, and the balance between TNF-alpha and
      the receptors. Fetal membranes collected from black and white women at term were
      maintained in an organ explant system and stimulated with lipopolysaccharide
      (LPS). TNF-alpha, soluble TNF receptors (sTNFR1 and sTNFR2) in culture media and
      membrane bound TNF receptors (TNFR1 and TNFR2) in tissue homogenates were
      measured. Molar ratio (TNF/sTNFR) was calculated between LPS stimulated and
      unstimulated (controls) cultures in both races. TNF-alpha was increased in both
      races after LPS stimulation and showed no difference between races (p=0.7). LPS
      decreased sTNFR1 in blacks, but increased in whites, showing a significant
      difference between races (p=0.001). In blacks sTNFR2 also decreased and increased
      in whites, but the results were not significant between races (p=0.4). Both TNFR1
      and TNFR2 were increased in blacks after LPS stimulation whereas no such changes
      were seen in whites compared to controls that were also significant between
      races. After LPS stimulation TNF-alpha bioavailability was increased in blacks
      with a drop in soluble receptors and with an increase in membrane receptors. This
      was not evident in whites because in whites soluble receptors were increased with
      no change in membrane receptors. Our data demonstrated that LPS stimulation
      results in a molar ratio switch favoring TNF-alpha biofunction in blacks, but not
      in whites.

PMID- 17517433
TI  - TRPC channels as STIM1-regulated store-operated channels.
AB  - Receptor-activated Ca(2+) influx is mediated largely by store-operated channels
      (SOCs). TRPC channels mediate a significant portion of the receptor-activated
      Ca(2+) influx. However, whether any of the TRPC channels function as a SOC
      remains controversial. Our understanding of the regulation of TRPC channels and
      their function as SOCs is being reshaped with the discovery of the role of STIM1
      in the regulation of Ca(2+) influx channels. The findings that STIM1 is an ER
      resident Ca(2+) binding protein that regulates SOCs allow an expanded and
      molecular definition of SOCs. SOCs can be considered as channels that are
      regulated by STIM1 and require the clustering of STIM1 in response to depletion
      of the ER Ca(2+) stores and its translocation towards the plasma membrane. TRPC1
      and other TRPC channels fulfill these criteria. STIM1 binds to TRPC1, TRPC2,
      TRPC4 and TRPC5 but not to TRPC3, TRPC6 and TRPC7, and STIM1 regulates TRPC1
      channel activity. Structure-function analysis reveals that the C-terminus of
      STIM1 contains the binding and gating function of STIM1. The ERM domain of STIM1
      binds to TRPC channels and a lysine-rich region participates in the gating of
      SOCs and TRPC1. Knock-down of STIM1 by siRNA and prevention of its translocation
      to the plasma membrane inhibit the activity of native SOCs and TRPC1. These
      findings support the conclusion that TRPC1 is a SOC. Similar studies with other
      TRPC channels demonstrate their regulation by STIM1 and indicate that all TRPC
      channels, except TRPC7, function as SOCs.

PMID- 17517434
TI  - Characterisation of TRPM8 as a pharmacophore receptor.
AB  - Some proteins of the transient receptor potential (TRP) family form temperature
      sensitive ion channels. One member of the melastatin (M) group, namely TRPM8 is
      activated by cold and cooling compounds such as menthol and icilin, and its gene
      is up-regulated in prostate cancer and other malignancies. Here we characterise
      the effects of the carboxamides WS-12, CPS-113, CPS-369, the carboxylic acid WS
      30 and the phosphine oxide WS-148 by Ca2+ imaging experiments and whole-cell
      patch-clamp recordings on TRPM8 expressing human embryonic kidney (HEK), lymph
      node prostate cancer (LNCaP) and dorsal root ganglia (DRG) cells. The cooling
      compounds introduced in this study, show a dose-dependent and reversible
      activation of TRPM8 with EC50 values in the nM to low microM range. The
      carboxamide WS-12 is most potent in activating TRPM8. It is selective, since
      other TRP proteins are not stimulated at muM concentrations and its efficacy with
      respect to TRPM8 is similar to the one of icilin. In summary, the compounds
      described in this study represent new tools to dissect TRPM8 functions and may
      serve as chemical leads for the development of additional TRPM8 agonists and
      novel antagonists. Such compounds may be beneficial for preventing noxious cold
      perception. They could also be useful in diagnosis and treatment of most common
      cancers in which the TRPM8 gene is up-regulated in comparison to the
      corresponding normal tissue.

PMID- 17517436
TI  - Influence of flow-through and renewal exposures on the toxicity of copper to
      rainbow trout.
AB  - We examined changes in water chemistry and copper (Cu) toxicity in three paired
      renewal and flow-through acute bioassays with rainbow trout (Oncorhynchus
      mykiss). Test exposure methodology influenced both exposure water chemistry and
      measured Cu toxicity. Ammonia and organic carbon concentrations were higher and
      the fraction of dissolved Cu lower in renewal tests than in paired flow-through
      tests. Cu toxicity was also lower in renewal tests; 96 h dissolved Cu LC(50)
      values were 7-60% higher than LC(50)s from matching flow-through tests. LC(50)
      values in both types of tests were related to dissolved organic carbon (DOC)
      concentrations in exposure tanks. Increases in organic carbon concentrations in
      renewal tests were associated with reduced Cu toxicity, likely as a result of the
      lower bioavailability of Cu-organic carbon complexes. The biotic ligand model of
      acute Cu toxicity tended to underpredict toxicity in the presence of DOC. Model
      fits between predicted and observed toxicity were improved by assuming that only
      50% of the measured DOC was reactive, and that this reactive fraction was present
      as fulvic acid.

PMID- 17517435
TI  - The long and arduous road to CRAC.
AB  - Store-operated calcium (SOC) entry is the major route of calcium influx in non
      excitable cells, especially immune cells. The best characterized store-operated
      current, I(CRAC), is carried by calcium release activated calcium (CRAC)
      channels. The existence of the phenomenon of store-operated calcium influx was
      proposed almost two decades ago. However, in spite of rigorous research by many
      laboratories, the identity of the key molecules participating in the process has
      remained a mystery. In all these years, multiple different approaches have been
      adopted by countless researchers to identify the molecular players in this
      fundamental process. Along the way, many crucial discoveries have been made, some
      of which have been summarized here. The last couple of years have seen
      significant breakthroughs in the field-identification of STIM1 as the store
      Ca(2+) sensor and CRACM1 (Orai1) as the pore-forming subunit of the CRAC channel.
      The field is now actively engaged in deciphering the gating mechanism of CRAC
      channels. We summarize here the latest progress in this direction.

PMID- 17517437
TI  - Mono- and dicarboxylic polypyridyl-Ru complexes as potential cell DNA dyes and
      transfection agents.
AB  - A ruthenium coordination complex, incorporating two highly extended pi-systems
      DIP and two carboxylic groups: [Ru(DIP)2(L-L)]2+ where DIP=4,7-diphenyl-1,10
      phenanthroline and L-L=4,4'-dicarboxy-2,2'-bipyridine, is found to be of
      biological interest. It constitutes an effective nuclear DNA dye for living
      cells: fluorescent, permeant, biocompatible, high Stokes shift. These features
      are commented in terms of hydrophobicity and DNA binding. In addition, this
      complex is shown to internalize a plasmid carrying the enhanced green fluorescent
      protein (EGFP) gene. Positive results are obtained for gene expression, which is
      related to condensation of the DNA by this ruthenium agent. This opens up an
      innovative transfection route based on metal complexes.

PMID- 17517438
TI  - Nonparametric statistical testing of EEG- and MEG-data.
AB  - In this paper, we show how ElectroEncephaloGraphic (EEG) and
      MagnetoEncephaloGraphic (MEG) data can be analyzed statistically using
      nonparametric techniques. Nonparametric statistical tests offer complete freedom
      to the user with respect to the test statistic by means of which the experimental
      conditions are compared. This freedom provides a straightforward way to solve the
      multiple comparisons problem (MCP) and it allows to incorporate biophysically
      motivated constraints in the test statistic, which may drastically increase the
      sensitivity of the statistical test. The paper is written for two audiences: (1)
      empirical neuroscientists looking for the most appropriate data analysis method,
      and (2) methodologists interested in the theoretical concepts behind
      nonparametric statistical tests. For the empirical neuroscientist, a large part
      of the paper is written in a tutorial-like fashion, enabling neuroscientists to
      construct their own statistical test, maximizing the sensitivity to the expected
      effect. And for the methodologist, it is explained why the nonparametric test is
      formally correct. This means that we formulate a null hypothesis (identical
      probability distribution in the different experimental conditions) and show that
      the nonparametric test controls the false alarm rate under this null hypothesis.

PMID- 17517439
TI  - Abnormal interleukin 1 receptor types I and II gene expression in eutopic and
      ectopic endometrial tissues of women with endometriosis.
AB  - Interleukin-1 (IL1) is believed to play a central role in the immuno-inflammatory
      process associated with endometriosis. IL1 triggers cell activation via its
      receptor type I (IL1R1), but its receptor type II (IL1R2) is known instead as a
      scavenger that buffers the cytokine's effects. Our previous studies have shown
      increased expression of IL1R1 in active endometriotic implants compared to normal
      and endometriosis women-derived endometrial tissues, and a simultaneous decrease
      in IL1R2 expression at the protein level. In the present study, in situ
      hybridization demonstrated a noticeable decrease in IL1R2 mRNA hybridization
      score in eutopic and matched ectopic endometrial tissues of women with
      endometriosis compared to normal women in the stroma (P<0.001 and P<0.001,
      respectively) and the epithelium (P<0.01 and P<0.05, respectively), whereas IL1R1
      mRNA hybridization score was higher only in the ectopic implants, with a
      statistically significant difference in the stroma (P<0.05). This was
      corroborated by RT-PCR analysis of IL1R1 and IL1R2 mRNAs in ectopic (P<0.05 and
      P<0.05, respectively) and matched eutopic (P=0.22 and P<0.05, respectively)
      endometrial tissues from women with endometriosis compared to endometrial tissues
      from normal women. The decrease in IL1R2 mRNA levels in eutopic endometrial
      tissue of endometriosis women, and the concomitant increase in IL1R1 mRNA levels
      in ectopic implants, reveal a profound defect in IL1R 1 and IL1R2 gene expression
      which may accentuate the capability of this tissue to respond to IL1 and favor
      its ectopic growth.

PMID- 17517440
TI  - Gender associations with chronic methylphenidate treatment and behavioral
      performance following experimental traumatic brain injury.
AB  - Evidence suggests that dopamine (DA) agonists improve cognition after traumatic
      brain injury (TBI). Methylphenidate (MPH) is a DA agonist that blocks the
      dopamine transporter (DAT). Moreover, female sex hormones modulate DAT
      expression. Therefore, the purpose of this study was to evaluate how MPH affects
      behavioral performance in male and female rats. Under anesthesia, rats underwent
      either controlled cortical impact (CCI) or sham injury operations. Beginning post
      operative day 1, rats received daily intraperitoneal injections of MPH (5mg/kg)
      or saline. Beam balance (BB) and beam-walking (BW) were assessed on post
      operative days 1-5. Exploratory behavior was assessed using an open field free
      choice novelty (FCN) task on day 13. Spatial memory was assessed with a Morris
      water maze (MWM) task on days 14-20. Multivariate analyses showed TBI females
      performed better than TBI males on both motor tasks (P<0.05 both comparisons),
      and MPH improved BB performance for both male and female injury groups (P=0.05)
      compared to their respective vehicle treated injury groups. Multivariate analysis
      showed that MPH enhanced MWM performance (spatial learning and retention) after
      TBI. Significant improvements were noted only in injured males treated with MPH
      compared to their vehicle control (P<0.05) with respect to improvements in memory
      acquisition and retention. Further, injured females treated with MPH had faster
      swimming speeds than all other groups (P<0.05 all comparisons), and MPH increased
      activity in TBI females but not males in the FCN task (P<0.05). These results
      suggest that MPH is beneficial after TBI. However there are gender specific drug
      differences in behavioral performance and sensitivity to treatment with MPH that
      may have implications for treatment efficacy and dosing clinically after TBI.

PMID- 17517441
TI  - Corticotropin releasing hormone receptor alterations elicited by acute and
      chronic unpredictable stressor challenges in stressor-susceptible and resilient
      strains of mice.
AB  - Stressors increase corticotropin releasing hormone (CRH) functioning in
      hypothalamic and frontal cortical brain regions, and thus may contribute to the
      provocation of anxiety and depressive disorder. As the effects of stressors on
      these behavioral changes are more pronounced in some strains of mice (e.g.,
      BALB/cByJ) than in others (e.g., C57BL/6ByJ), the present investigation assessed
      whether acute and chronic stressors would differentially influence CRH receptor
      immunoreactivity (ir-CRHr) and CRH receptor mRNA expression (CRH(1) and CRH(2))
      in the orbital frontal cortex (OFC) of these strains. An acute noise stressor,
      and to a greater extent a chronic, variable stressor regimen reduced ir-CRHr in
      BALB/cByJ mice. In contrast, in the hardier C57BL/6ByJ mice the acute stressor
      increased ir-CRHr in portions of the OFC, whereas a chronic stressor tended to
      reduce ir-CRHr. However, whereas the acute stressor did not influence CRH(1) mRNA
      expression, the chronic stressor increased CRH(1) mRNA expression in both mouse
      strains. The CRH(2) expression appeared in low abundance in both strains and was
      unaltered by the stressor. In addition to the OFC variations, quantitative
      immunohistochemistry indicated that the chronic stressor treatment increased CRH
      immunoreactivity in the median eminence of C57BL/6ByJ mice, but co-expression of
      CRH and arginine vasopressin (AVP) immunoreactivity was not provoked by the
      stressors. The data support the view that stressors provoke marked variations of
      ir-CRHr in the OFC that might contribute to the differential anxiety/depression
      like profiles ordinarily apparent in the stressor-vulnerable and -resilient mouse
      strains.

PMID- 17517442
TI  - Effects of an intervention on health behaviors of older coronary artery bypass
      (CAB) patients.
AB  - Coronary artery bypass (CAB) patients are older increasingly more often than
      before. Effectiveness of cardiac rehabilitation among the elderly is not yet
      adequately known about. The purpose was to describe short-term (3-month),
      intermediate (6-month), and long-term (12-month) effects of health counseling,
      guidance, and adjustment education in groups on health, health behaviors, and
      functional abilities among older CAB patients. The study population was
      randomized to an intervention group (IG=49) and a control group (CG=68). Prior to
      CAB, intervention included one guidance and counseling group session and four
      sessions within 12 months following CAB. Intervention had positive effects on
      exercise activities, use of alcohol, and functional abilities among all
      participants, and on frequency of eating visible fat, fresh greens and vegetables
      among men. The intervention was effective with some exercise activities and
      functional abilities persisting for at least 1 year following CAB. Similar
      interventions may be arranged for older people. Health care professionals need to
      guide and encourage older people in their efforts to participate in them.

PMID- 17517443
TI  - A model (BSurvE) for evaluating national surveillance programs for bovine
      spongiform encephalopathy.
AB  - Our BSurvE spreadsheet model estimates the BSE prevalence in a national cattle
      population, and can be used to evaluate and compare alternative strategies for a
      national surveillance program. Each individual surveillance test has a point
      value (based on demographic and epidemiological information) that reflects the
      likelihood of detecting BSE in an animal of a given age leaving the population
      via the stated surveillance stream. A target sum point value for the country is
      calculated according to a user-defined design prevalence and confidence level,
      the number of cases detected in animals born after the selected starting date and
      the national adult-herd size. Surveillance tests carried out on different sub
      populations of animals are ranked according to the number of points gained per
      unit cost, and the results can be used in designing alternative surveillance
      programs.

PMID- 17517444
TI  - Pre-treatment number of clonogenic cells and their radiosensitivity are major
      determinants of local tumour control after fractionated irradiation.
AB  - OBJECTIVE: The response of tumours to fractionated radiotherapy is determined by
      many factors including repopulation, reoxygenation, the number of clonogenic
      cells, and their intrinsic radiosensitivity. However, after single radiation
      doses given under conditions of clamp hypoxia, the dose to control a tumour
      locally is dependent only on the number of clonogenic cells and their cellular
      radiosensitivity. Therefore, these parameters were investigated using local
      control after single doses given under hypoxia, to predict the outcome of
      fractionated irradiation. MATERIALS AND METHODS: Ten hSCC cell lines (FaDu, UT
      SCC-15, UT-SCC-14, XF354, UT-SCC-5, UT-SCC-45, SAS, CAL-33, UT-SCC-8, and HSC-4)
      were transplanted subcutaneously into the right hind-leg of NMRI nude mice. At
      7mm in diameter, tumours were irradiated either with graded single doses under
      clamp blood flow conditions (n=873) or with 30 graded fractions within 6 weeks
      (n=905) under ambient conditions. Local tumour control was determined 120 days
      after irradiation. Radiation response was quantified in terms of TCD(50), i.e.
      the dose required to control 50% of tumours locally. RESULTS: Ten tumour lines
      investigated showed a pronounced heterogeneity in both TCD(50(30fx/6w)) after
      fractionated irradiation and TCD(50(SDclamp)) after single dose irradiation.
      TCD(50(30fx/6w)) varied between 45Gy for UT-SCC-45 and 127Gy for SAS;
      TCD(50(SDclamp)) varied between 42Gy for UT-SCC-14 and 66Gy for CAL-33. Two
      tumours were excluded from further analysis due to immunogenicity or non-defined
      TCD(50). Linear regression analysis revealed a significant positive correlation
      between TCD(50(SDclamp)) and TCD(50(30fx/6w)) (R(2)=0.82, p=0.002). CONCLUSIONS:
      Significant association between TCD(50(SDclamp)) and TCD(50(30fx/6w)) suggests
      that the pre-treatment number of clonogenic tumour cells and their cellular
      radiosensitivity have a major impact on local control after fractionated
      radiotherapy.

PMID- 17517445
TI  - Extent of satisfaction with tablets and food-timing in sulphonylurea-treated
      diabetes.
AB  - This study measured patient views about following tablet-taking and food-timing
      recommendations in Type 2 diabetes. Two new questionnaires were validated.
      Outpatients with Type 2 diabetes treated with sulphonylurea agents (n=131)
      completed the seven-item Diabetes Tablet Treatment Questionnaire (DTTQ) and nine
      item Diabetes Food Timing Questionnaire (DFTQ). Mean glycosylated haemoglobin
      (HbA1c) was 7.8% (S.D. 1.8%). At least 74% had optimal DTTQ item scores for
      tablet-taking as recommended, difficulty taking tablets, side effects, perceived
      hypoglycaemia and willingness to continue current tablets, but 71% scored sub
      optimally regarding recent hyperglycaemia. Under half scored optimally on DFTQ
      items concerning eating at recommended times, difficulty with food-timing,
      denying oneself food and guilt about eating. Principal components and reliability
      analyses identified a two-item tablet problem scale within the DTTQ (alpha 0.72)
      and a seven-item food-timing problem scale in the DFTQ (alpha 0.77). Satisfaction
      and adherence were not closely related to glycaemic control. Only scores for
      perceived hyperglycaemia (r=0.38), perceived hypoglycaemia (r=-0.24) and
      satisfaction to continue current tablets (r=-0.20) correlated significantly with
      HbA1c. Clinicians found that the DTTQ helped to raise tablet-taking issues
      otherwise missed in consultations. Both questionnaires can be used to guide the
      need for focussed discussion, educational intervention and/or treatment change
      and to evaluate their impact.

PMID- 17517446
TI  - Effects of leptin on intake of specific micro- and macronutrients in a woman with
      leptin gene deficiency studied off and on leptin at stable body weight.
AB  - In this report, we examine the effects of leptin on the intake of specific macro-
      and micronutrients in a female patient with leptin gene deficiency. The patient
      was studied off and on leptin at stable body weight, within the normal to mildly
      overweight range. The data were obtained by detailed dietary assessments,
      measuring dietary intakes by weighed food and fluid consumption records, and
      analyzed using nutrition analysis software. Overall, significant differences were
      found in the off versus on leptin treatment periods in the following categories:
      (i) macronutrients: kilocalories, protein, carbohydrates, monounsaturated fats,
      MFA 18:1 oleic and total fiber; (ii) vitamins: vitamin C, pyridoxine and
      pantothenic acid; (iii) minerals: potassium, magnesium, copper and chromium; and
      amino acids: threonine, lysine and histidine. The nutritional data from this
      study indicates a direct link between the effects of leptin and ingestion of
      several specific micronutrients. The mechanisms underlying these effects warrant
      further investigation and study.

PMID- 17517447
TI  - Impact of a five-year surveillance of central venous catheter infections in the
      REACAT intensive care unit network in France.
AB  - Central venous catheter (CVC)-related infections (CRIs) are a key target for
      infection control in intensive care units (ICUs). The aim of this study was to
      describe temporal trends of CRI incidence in a network of volunteer ICUs in
      Northern France. During a 4 month surveillance period each year, all CVCs in
      place for more than 48h were prospectively followed until removal or patient
      discharge. Standard clinical and microbiological criteria were used to define
      colonization and CRI. The standardized incidence ratio (SIR) was estimated by
      dividing the number of observed CRIs by the number of expected CRIs, which was
      computed using a logistic regression model including risk factors for CRI. CRI
      incidence and SIR were fed back to ICUs as a benchmark at the end of each period.
      From 2001 to 2005, 135 ICUs participated for at least one surveillance period.
      Overall, 11 703 CVC in 9182 patients (122 495 CVC-days) were included. CRI
      incidence was 2.8 per 1000 CVC-days. Among 35 ICUs that participated for three or
      more consecutive periods, CRI incidence decreased significantly by 58.6%. SIR
      also decreased significantly from the first to the third surveillance period in
      these ICUs. These results suggest that surveillance programmes have a significant
      impact on CRI risk in ICUs and remain an important strategy for combating
      nosocomial infections in these settings.

PMID- 17517449
TI  - Synthesis and antimicrobial studies of novel dichlorofluorophenyl containing
      aminotriazolothiadiazines.
AB  - Dichlorofluorophenyl containing aminotriazolothiadiazines (6) were synthesized by
      initial condensation of 2-chloro-N-(substituted phenyl) acetamides (4) with
      triazole (3) and further cyclization using POCl(3). The structures of newly
      synthesized compounds were confirmed by IR, NMR, mass and elemental analysis. All
      the compounds were screened for their antibacterial and antifungal activities.
      Compounds 5a, 5e, 5n, 5o, 6a, 6n, and 6o showed very good antibacterial and
      antifungal activities at 6.25 microg/ml concentrations.

PMID- 17517450
TI  - BMR variability in women of different weight.
AB  - BACKGROUND & AIMS: Non-exercise activity thermogenesis (NEAT) and substrate
      oxidation are significant components of Energy Balance; their regulation may be
      modulated according to nutritional status and their impairment has been advocated
      as a factor facilitating the development of excess body fat. METHODS: In this
      study body composition, resting metabolic rate (RMR), fidgeting as a component of
      NEAT and respiratory quotient (RQ), an index of preferential substrate oxidation,
      have been evaluated in 80 young women: 20 restrictive anorexia nervosa (rAN: BMI
      15.1+/-1.6 kg/m(2)); 20 constitutional leanness (CL: BMI 17.2+/-1.0); 20 obese
      patients (Ob: BMI 43.8+/-10.0) and 20 controls (CTR: BMI 21.7+/-2.4). RESULTS:
      Fat free mass, fat mass and RMR progressively increased from rAN to Ob (p <
      0.05). Fidgeting was higher in CL (67.2+/-27.2 kcal; p < 0.05) than in the other
      groups. Lipid oxidation, evaluated with RQ showed a negative correlation with
      fidgeting in CL (r=-0.433; p<0.05) and positive in Ob (r=0.572; p<0.05) and in
      rAN (r=0.434; p<0.05). CONCLUSION: Our findings support the regulatory function
      of NEAT, its protective role to prevent excess body fat accumulation and its
      positive relation with fat oxidation in CL.

PMID- 17517451
TI  - Effectiveness of a trivalent serogroup A/C/W135 meningococcal polysaccharide
      vaccine in Burkina Faso, 2003.
AB  - Following a large Neisseria meningitidis W135 (NmW135) epidemic in Burkina Faso
      (BF) during 2002, a newly licensed trivalent A/C/W135 meningococcal
      polysaccharide vaccine was introduced in 2003. We conducted a case-control study
      to assess the vaccine effectiveness (VE) against meningococcal disease. Thirty
      two N. meningitidis A (NmA) and 3 NmW135 meningitis cases were enrolled and
      matched by age-neighborhood to 103 controls. After adjusting for confounding risk
      factors, VE against NmA or NmW135 was 83.6% (95% CI 31.8-97.0, p=0.01) for
      persons with verified vaccination. VE against probable/definite NmA alone was
      94.0% (95% CI 58.7-99.0, p=0.0003). Low number of NmW135 cases did not allow
      estimation of VE against NmW135 alone. The vaccine was highly effective against
      the epidemic. Since 2003, the trivalent vaccine continues to be effectively used
      in Africa for the control of meningococcal disease epidemics.

PMID- 17517452
TI  - Biological diagnosis of meningococcal meningitis in the African meningitis belt:
      current epidemic strategy and new perspectives.
AB  - Laboratory diagnosis is an essential component in surveillance of meningococcal
      epidemics, as it can inform decision-makers of the Neisseria meningitidis
      serogroup(s) involved and the most appropriate vaccine to be selected for mass
      vaccination. However, countries most affected face real limitations in laboratory
      diagnostics, due to lack of resources. We describe current diagnostic tools and
      examine their cost-effectiveness for use in an epidemic context. The conclusion
      is that current WHO recommendations to use only the latex agglutination assay
      (Pastorex) at epidemic onset is cost-effective, but recently developed rapid
      diagnostic tests for the major epidemic-causing meningococcal serogroups may
      prove a breakthrough for the future.

PMID- 17517453
TI  - Risk mapping and early warning systems for the control of meningitis in Africa.
AB  - Epidemics of meningococcal meningitis in Africa have plagued the continent for
      over a century. These epidemics have a strong association with the environment
      and efforts are being made to develop models to predict both their location and
      their incidence. This review describes the predictive models based on
      climate/environmental information currently available, describes work in
      progress, and presents evidence that the distribution of the epidemics is
      changing in a pattern that is compatible with changes in the environment.
      Discussion of priorities for research in the context of the new conjugate
      vaccines in Africa is also provided.

PMID- 17517454
TI  - Populations of pharyngeal meningococci in Niger.
AB  - This study investigated the carriage of Neisseria meningitidis group W135
      (NmW135) belonging to sequence type (ST)-2881, ST-11 and NmA ST-7, as these three
      lineages have been responsible for sporadic cases in 2003 in Niamey (Niger). ST-7
      and ST-11 were also the two genotypes involved in recent outbreaks in the African
      meningitis belt. Among the 97 Nm isolates obtained from 287 schoolchildren
      swabbed three times, 1 was identified as NmA, 34 as NmW135, 8 as NmY and 54 were
      non-groupable (NG). Among the 86 isolates genotyped, 59.3% belonged to ST-192,
      24.4% to ST-2881, 5.8% to ST-2880, 4.6% to ST-175, 3.5% to ST-4899, 1.2% to ST-11
      and 1.2% to ST-7. Most of the isolates recovered were weakly pathogenic Nm NG ST
      192 and NmW135 ST-2881. These results, although preliminary, are important to
      consider before introduction of a NmA conjugate meningococcal vaccine in Africa.

PMID- 17517448
TI  - The role of glutamate transporters in neurodegenerative diseases and potential
      opportunities for intervention.
AB  - Extracellular concentrations of the predominant excitatory neurotransmitter,
      glutamate, and related excitatory amino acids are maintained at relatively low
      levels to ensure an appropriate signal-to-noise ratio and to prevent excessive
      activation of glutamate receptors that can result in cell death. The latter
      phenomenon is known as 'excitotoxicity' and has been associated with a wide range
      of acute and chronic neurodegenerative disorders, as well as disorders that
      result in the loss of non-neural cells such as oligodendroglia in multiple
      sclerosis. Unfortunately clinical trials with glutamate receptor antagonists that
      would logically seem to prevent the effects of excessive receptor activation have
      been associated with untoward side effects or little clinical benefit. In the
      mammalian CNS, the extracellular concentrations of glutamate are controlled by
      two types of transporters; these include a family of Na(+)-dependent transporters
      and a cystine-glutamate exchange process, referred to as system X(c)(-). In this
      review, we will focus primarily on the Na(+)-dependent transporters. A brief
      introduction to glutamate as a neurotransmitter will be followed by an overview
      of the properties of these transporters, including a summary of the presumed
      physiologic mechanisms that regulate these transporters. Many studies have
      provided compelling evidence that impairing the function of these transporters
      can increase the sensitivity of tissue to deleterious effects of aberrant
      activation of glutamate receptors. Over the last decade, it has become clear that
      many neurodegenerative disorders are associated with a change in localization
      and/or expression of some of the subtypes of these transporters. This would
      suggest that therapies directed toward enhancing transporter expression might be
      beneficial. However, there is also evidence that glutamate transporters might
      increase the susceptibility of tissue to the consequences of insults that result
      in a collapse of the electrochemical gradients required for normal function such
      as stroke. In spite of the potential adverse effects of upregulation of glutamate
      transporters, there is recent evidence that upregulation of one of the glutamate
      transporters, GLT-1 (also called EAAT2), with beta-lactam antibiotics attenuates
      the damage observed in models of both acute and chronic neurodegenerative
      disorders. While it seems somewhat unlikely that antibiotics specifically target
      GLT-1 expression, these studies identify a potential strategy to limit
      excitotoxicity. If successful, this type of approach could have widespread
      utility given the large number of neurodegenerative diseases associated with
      decreases in transporter expression and excitotoxicity. However, given the
      massive effort directed at developing glutamate receptor agents during the 1990s
      and the relatively modest advances to date, one wonders if we will maintain the
      patience needed to carefully understand the glutamatergic system so that it will
      be successfully targeted in the future.

PMID- 17517455
TI  - The epidemiology of Neisseria meningitidis meningitis in Togo during 2003-2005.
AB  - Few reports documenting the epidemiology of Neisseria meningitidis (Nm) serogroup
      W135 exist, and none from Togo. During 2003-2005, we conducted acute bacterial
      meningitis surveillance at three major reference hospitals in Togo. Of 116 Nm
      identified, 83 (71%) were NmA, 23 (20%) were NmW135, and 10 (9%) did not have a
      serogroup identified. Nine percent of NmW135 cases and 35% of NmA cases occurred
      among those aged 15 years or older. The two hospitals in central Togo reported
      23% of all Nm cases and 78% of NmW135 cases. Twelve of the 23 NmW135 cases
      occurred during February-March 2003, while the remaining 11 occurred sporadically
      over the remaining 18 months of the study. NmW135 meningitis showed pronounced
      temporal and geographic clustering and occurred almost exclusively among those
      younger than 15 years old. By the 2004-2005 epidemic season, NmW135 had largely
      disappeared from Togo for unknown reasons.

PMID- 17517456
TI  - Corneal and conjunctival toxicity of disinfectants--assessing safety for use with
      ophthalmic surgical instruments.
AB  - We investigated the corneal toxicity of ortho-phthalaldehyde (Cidex OPA, Johnson
      and Johnson K.K.) and its predecessor glutaraldehyde (Cidex, Johnson and Johnson
      K.K.). We made primary cultures of porcine and human corneal endothelial cells.
      Commercially available cell lines were also used including human, bovine, and
      rabbit corneal epithelium and human conjunctival cells. Following incubation for
      two days, cell survival was measured using a WST-1 assay for endothelia and a MTT
      assay for the other cells. Test solutions included 2.25% and 3.5% glutaraldehyde
      and 0.55% ortho-phthalaldehyde. Cell survival was presented as a percentage of
      the control value. ortho-phthalaldehyde displayed less toxicity than
      glutaraldehyde for all cell types tested. As expected 3.5% glutaraldehyde was
      slightly more toxic than 2.25% glutaraldehyde. When primary human corneal
      endothelial cultures were exposed to ortho-phthalaldehyde, the survival rates
      were 88% for 100-fold dilutions and 95% for 500-fold dilutions. The survival
      rates for all cells tested were greater than 90% when dilutions of 1000-fold or
      more were used. In conclusion, the corneal toxicity of glutaraldehyde and ortho
      phthalaldehyde appears to be within safe levels following washing procedures and
      therefore the use of these disinfectants may be suitable for selected ophthalmic
      surgical instruments in urgent or under-equipped circumstances.

PMID- 17517457
TI  - Variation in deliberate self-harm around Christmas and New Year.
AB  - Seasonal and temporal variations in suicide by patient and demographic groups,
      though important, have been investigated infrequently. This study examined
      patterns of non-fatal deliberate self-harm (DSH) during Christmas and New Year
      (from December 16th to January 6th) by specific patient and demographic group.
      The sample comprised 19,346 people who presented with 31,369 episodes of DSH to a
      general hospital Emergency Department in Oxford, UK. Autoregression analysis of
      all episodes from 1976 to 2003 (controlling for day of the week, month and year)
      revealed significant reductions (-30% to -40%) in the occurrence of DSH compared
      with expected numbers on each day from December 19th to 26th (except the 23rd),
      though no significant increase was found on any of the subsequent 11 days. When
      analysed separately, young people aged under 25 years showed decreases (-60%) in
      the occurrence of DSH on several days throughout Christmas (p<0.001) and New Year
      (p<0.01). Patients with partner relationship problems showed a decrease 3 days
      before Christmas Day (-80%, p<0.001) and an increase on New Year's Day (+100%,
      p<0.01). Patients with family relationship problems showed decreases before
      Christmas and after New Year (-60%, p<0.01). Patients with social isolation
      problems, or a previous history of DSH showed decreases (-60%, p<0.01) before
      Christmas only. Patients who used alcohol at the time of DSH or in the 6h
      beforehand, but did not chronically misuse alcohol, showed an increase (+250%,
      p<0.01) on New Year's Day. There was no significant variation in the occurrence
      of DSH for patient groups with either low/medium or high suicide intent. The
      findings elucidate how social and individual factors may interact in contributing
      to DSH. They are of theoretical interest, and have important clinical
      implications regarding identification of patient groups especially susceptible to
      DSH at New Year.

PMID- 17517458
TI  - Visual-perceptual abilities in healthy controls, depressed patients, and
      schizophrenia patients.
AB  - Previous studies have suggested a right hemineglect in schizophrenia, however few
      assessed possible visual-perceptual implication in this lateralized anomaly. A
      manual line bisection without (i.e., lines presented on their own) or with a
      local cueing paradigm (i.e., a number placed at one or both ends of the line) and
      the Motor-free Visual Perceptual Test-Vertical format (MVPT-V) were used to
      assess the visual-perceptual abilities of healthy controls, schizophrenia and
      depressed patients. Whereas healthy controls and depressed patients showed a non
      significant leftward bias in manual line bisection, schizophrenia patients
      bisected significantly to the left of the true centre of the line. Interestingly,
      the pattern of performances in response to the local cueing paradigm was similar
      in depressed and schizophrenia patients such that both groups demonstrated a
      significant change in their bisection performance only in response to a cue
      placed at the right extremity of the line (control performance was modified by
      cues at either end of the line). Finally, in the MVPT-V, schizophrenia patients
      were impaired relative to the other two groups, especially in the spatial working
      memory and visual closure categories. These results suggest that: 1/a deficit
      towards the right hemifield, consistent with a mild form of right hemineglect,
      can be observed in schizophrenia; 2/lateralized anomalies could also be observed
      in depression using an appropriate tool such as manual line bisection;
      3/performances in the MVPT-V suggested that a simple visual-perceptual deficit
      could not explain the lateralized anomaly observed in the manual line bisection,
      as it is the case in the hemineglect syndrome.

PMID- 17517459
TI  - Protective effect of Rumex patientia (English Spinach) roots on ferric
      nitrilotriacetate (Fe-NTA) induced hepatic oxidative stress and tumor promotion
      response.
AB  - In this communication, we document the antioxidant potential of ethanolic extract
      of Rumex patientia L. (Polygonaceae) roots and its chemopreventive effects
      against Fe-NTA mediated hepatic oxidative stress, hepatotoxicity and tumor
      promotion response. The extract exhibited high polyphenolic content, potent
      reducing power and significantly scavenged free radicals (including several
      reactive oxygen species (ROS) and reactive nitrogen species (RNS)). The extract
      also significantly and dose dependently protected against oxidative damage to
      lipids and DNA. These results indicated R. patientia root extract to exert a
      potent antioxidant activity in vitro. The efficacy of extract was also evaluated
      in vivo and it was found to exert a potent protective affect in acute oxidative
      tissue injury animal model: ferric nitrilotriacetate (Fe-NTA) induced
      hepatotoxicity in mice. Administration of Fe-NTA (9 mg/kg body weight, i.p.) to
      mice led to a significant oxidative stress and allied damage in liver tissues and
      induced hyperproliferation. A significant depletion was observed in GSH content
      and enzymes implicated in its metabolism. Attenuation also occurred in activities
      of other hepatic antioxidant enzymes including SOD, CAT, and GPX. Fe-NTA also
      incited hyperproliferation response elevating ornithine decarboxylase activity
      and [(3)H]-thymidine incorporation into DNA. Histopathological investigations and
      liver function tests (LFT) indicated Fe-NTA to cause extensive hepatic damage.
      However, prophylactic treatment with R. patientia root extract at a dose regimen
      of 100-200mg/kg body weight for a week not only restored hepatic antioxidant
      armory close to normal, but also significantly precluded oxidative damage
      restoring normal hepatic architecture and levels of hepatic damage markers. The
      data obtained in the present study illustrates R. patientia roots to possess
      potent antioxidant and free radical scavenging activities and thwart oxidative
      damage and hyperproliferation in hepatic tissues.

PMID- 17517460
TI  - Perceptibility and acceptability of CIELAB color differences in computer
      simulated teeth.
AB  - OBJECTIVES: To determine the perceptibility and acceptability of tooth color
      differences using computer-generated pairs of teeth with simulated gingival
      displayed on a calibrated color monitor using appropriate signal detection theory
      methodology (SDT). METHODS: Twelve dental professionals (four from each of the
      following groups: dentists, dental auxiliaries, and fixed prosthodontic
      technicians) and four dental patients served as subjects. Responses to tooth
      color differences (DeltaE) were measured on each of the three principal axes of
      CIELAB color space (L*, a*, and b*). As a control, responses to DeltaE=0 (the
      false alarm rate) were also measured in the same experimental session. RESULTS:
      No group differences among subjects were found. All gave 50% match or acceptance
      points that averaged about 1.0 DeltaE units in the L* and a* directions, and 2.6
      units in the b* direction. False alarm rates across all subjects averaged 27% (4
      55%) and 28% (0.4-61%), respectively, for perceptibility and acceptability. A
      reanalysis of the data based on SDT, which takes subjects' false alarm rates into
      account, gave somewhat larger color difference thresholds. CONCLUSIONS: Color
      difference thresholds for our simulated teeth are generally in line with and
      extend results obtained with studies using "real" dental materials. No
      differences between thresholds for acceptability versus perceptibility were
      found. Furthermore, subjects often reported color differences when none existed,
      and this behavior needs to be factored into any determination of quality control
      standards for the fabrication of dental prostheses.

PMID- 17517461
TI  - Cell fate specification in the mammalian telencephalon.
AB  - A fundamental feature of neural development in vertebrates is that different cell
      types are generated in a precise temporal sequence, first neurons, followed by
      oligodendrocytes and astrocytes. The mechanisms underlying these remarkable
      changes in progenitor fate during development are not well understood, but are
      thought to include both changes in the intrinsic properties of neural progenitors
      and changes in their signaling environment. I discuss the mechanisms that control
      the specification of neuronal, astroglial and oligodendroglial fates, focusing on
      the mammalian telencephalon, one of the most extensively used models to study
      neural specification mechanisms in vertebrates. I first consider the multiple
      extracellular signals that have been implicated in neural fate specification.
      Their roles are often complex, with the same signals having different effects at
      different developmental stages, and different signaling pathways interacting
      extensively. The selection of a particular cell fate ultimately results from the
      integration of multiple signals. Signaling pathways regulate cell fates by
      modulating the expression and activity of numerous transcription factors in
      neural stem cells. I discuss how transcription factors also act in a
      combinatorial manner to determine progenitor fates, with individual factors
      promoting the generation of one or two cell types and repressing alternative
      fate(s). Finally, I discuss the many levels of regulation involved in preventing
      premature astrocyte differentiation during neurogenesis, and later on in
      controlling the transition from neurogenesis to gliogenesis.

PMID- 17517462
TI  - Pregnancy outcome in obese and morbidly obese gestational diabetic women.
AB  - OBJECTIVE: We sought to determine whether pregnancy outcome differs between obese
      and morbidly obese GDM patients and to assess pregnancy outcome in association
      with mode of treatment and level of glycemic control. METHODS: A cohort study of
      4,830 patients with gestational diabetes (GDM), treated in the same center using
      the same diabetic protocol, was performed. Obesity was defined as prepregnancy
      BMI >30 and <35 kg/m(2); morbid obesity was defined as prepregnancy BMI >or=35
      kg/m(2). Well-controlled GDM was defined as mean blood glucose <105 mg/dl.
      Pregnancy outcome measures included the rates of large for gestational age (LGA)
      and macrosomic babies, metabolic complications, the need for NICU admission
      and/or respiratory support, rate of shoulder dystocia, and the rate of cesarean
      section. RESULTS: Among the GDM patients, the rates of obesity and morbid obesity
      were 15.7% (760 out of 4830, BMI: 32.4+/-1.6 kg/m(2)) and 11.6% (559 out of 4830,
      BMI: 42.6+/-2.2 kg/m(2)), respectively. No differences were found with regard to
      maternal age, ethnicity, gestational age at delivery or oral glucose tolerance
      test (OGTT) results. Moreover, similar rates of cesarean section, fetal
      macrosomia, shoulder dystocia, composite outcome, and metabolic complications
      were noted. Insulin treatment was initiated for 62% of the obese and 73% of the
      morbidly obese GDM patients (P<0.002). Similar rates of obese and morbidly obese
      patients achieved desired levels of glycemic control (63% versus 61%,
      respectively). In both obese and morbidly obese patients who achieved a desired
      level of glycemic control (<105 mg/dl), no difference was found in pregnancy
      outcome except that both neonatal metabolic complications and composite outcomes
      were more prevalent in diet-treated subjects in comparison to insulin-treated GDM
      patients. CONCLUSION: In obese women with GDM, pregnancy outcome is compromised
      regardless of the level of obesity or treatment modality.

PMID- 17517464
TI  - Influence of pyrene combination state in soils on its treatment efficiency by
      Fenton oxidation.
AB  - Interactions of hydrophobic organic compounds (HOCs) with soil organic matter
      (SOM) determine their combination state in soils, and therefore strongly
      influence their mobility, bioavailability, and chemical reactivity. Contact time
      (aging) of an HOC in soil also strongly influences its combination state and
      environmental fate. We studied Fenton oxidation of pyrene in three different
      soils to reveal the influences of SOM, contact time, and combination state on the
      efficiency of vigorous chemical reactions. Pyrene degradation efficiency depended
      strongly on the dose of oxidant (H(2)O(2)) and catalyst (Fe(2+)); the greatest
      degradation was achieved at an oxidant to catalyst molar ratio of 10:1. Pyrene
      degradation differed among the three soils, ranging from 65.4% to 88.9%. Pyrene
      degradation efficiency decreased with increasing SOM content, and the aromatic
      carbon content in SOM was the key parameter. We hypothesize that pyrene molecules
      that combine with the compact net structure of aromatic SOM are less accessible
      to Fenton oxidation. Furthermore, pyrene degradation efficiency decreased
      considerably after aged for 30 days, but further aging to 60 and 180 days did not
      significantly change degradation efficiency. The Fenton oxidation efficiency of
      pyrene in both unaged and aged soils was greater than the corresponding
      desorption rate during the same period, perhaps because Fenton reaction can make
      pyrene more accessible to the oxidant through the enhancement of HOCs' desorption
      by generating reductant species or by destroying SOM through oxidation.

PMID- 17517465
TI  - Emission of CO2, CH4 and N2O from freshwater marsh in northeast of China.
AB  - The wetlands play an important role in carbon storage, especially at high
      latitudes, at which they store nearly one-third of global soil carbons. However,
      few studies have investigated the emissions of CO(2), CH(4) and N(2)O in the long
      term, especially effects of freeze-thaw cycles on these gases emissions in
      freshwater marsh ecosystems. In this paper, we collected greenhouse gas emission
      data from a freshwater marsh area in China for 4 years, evaluated their release
      variables and speculated on their potential atmospheric impact. For this paper,
      we report on the CO(2), CH(4) and N(2)O emission rates recorded from June 2002 to
      November 2005 in the Sanjiang Plain of northeast China. We measured their
      interannual variations and fluctuations, as well as factors affecting their
      emissions, and estimated their regulation and freeze-thaw cycle impacts. Our
      results revealed obvious CO(2) and CH(4) emission fluctuations during the winter
      months, and during the freeze-thaw cycle, and a strong interannual variation
      during the growing season. Overall, we documented a close relationship between
      the CO(2) and CH(4) emissions, implicating some regulatory commonality. We
      determined that the marsh was a N(2)O sink during the winter, but a significant
      source of N(2)O during the freeze-thaw cycle as the temperature increased,
      especially in early summer. During the thaw-freeze period, the N(2)O levels were
      positively correlated with the water depth. Additionally, water depth greatly
      governed the interannual variation of the N(2)O emissions from the marshes during
      the thaw-freeze period.

PMID- 17517466
TI  - An environmental perspective of the post-tsunami scenario along the coast of
      Tamil Nadu, India: role of sand dunes and forests.
AB  - An endeavor to feel the pulse of a coast devastated by a powerful oceanographic
      event is made. Results of field investigations along Tamil Nadu seaside revealed
      that the tsunami of December 2004 demolished dwellings within strips ranging from
      6 to 132 m (average width, 41 m) from the dune, and flooded up to 862 m (average,
      247 m) from the shore. The event damaged sand dunes, ripped dune vegetation,
      created new water bodies and shattered high value assets. Comparatively,
      casuarina forests performed remarkably. Uprooting of trees was exclusively
      restricted to a frontal strip ranging from 5 to 25 m (average width, 14 m)
      nearest to the shore where the maximum wave run-up was 6.5m above sea level. Sand
      dunes in general, and casuarina forests in particular, possess an innate capacity
      to dissipate powerful waves. This inference is supported by (a) negligible over
      wash along belts characterized by high dune complexes, (b) intact villages
      shielded by dense forests as well as sand dunes, and (c) maximum destruction of
      open beach front influenced by intense human activity. In this context, the
      coastal regulation zone (CRZ) Notification of 1991 offers sufficient scientific
      validity to be endorsed. However, post-tsunami ecosystem management initiatives
      lack a scientific basis. Therefore, a coastal hazards policy, that considers
      adaptation, dune restoration and forested buffer zones, is a sustainable long
      term option for Indian coasts.

PMID- 17517468
TI  - Editorial comment on: The role of endoscopic treatment in the management of grade
      V primary vesicoureteral reflux.

PMID- 17517467
TI  - The role of endoscopic treatment in the management of grade v primary
      vesicoureteral reflux.
AB  - OBJECTIVES: Although endoscopic treatment provides a high rate of success in
      children with grades II-IV vesicoureteral reflux (VUR), its role in the
      management of grade V reflux has been questioned. In this study we reviewed our
      21-yr experience of endoscopic treatment in children with grade V primary VUR.
      METHODS: We retrospectively reviewed the medical records of 132 children who
      underwent endoscopic treatment for primary grade V reflux from 1984 to 2004. VUR
      was unilateral in 39 patients and bilateral in 34, and 59 patients had
      ipsilateral grade V reflux with a lower grade of VUR on the contralateral side.
      Endoscopic treatment was performed in a total of 166 grade V ureters;
      polytetrafluoroethylene was used from 1984 to 2000 and dextranomer/hyaluronic
      acid from 2001 to 2004. Median follow-up was 12.2 yr and mean follow-up was 13.4
      yr. RESULTS: VUR was completely resolved after first injection in 88 (53%)
      ureters and downgraded to grade I or II in 26 (15.7%). VUR resolved after a
      second and third injection in 36 (21.7%) and 10 (6%) of ureters, respectively.
      Endoscopic treatment failed to correct VUR in 6 (3.6%) ureters, requiring
      ureteral reimplantation in 5 and nephrectomy in 1. Thirteen patients developed
      urinary tract infections during the follow-up period, and on investigation 9
      ureters (5.4%) had recurrence of VUR. No injection or morbidity related to tissue
      augmenting substances was noted in any patient. CONCLUSION: Endoscopic treatment
      should be the first-line of treatment in management of grade V vesicoureteral
      reflux.

PMID- 17517469
TI  - Editorial comment on: The role of endoscopic treatment in the management of grade
      V primary vesicoureteral reflux.

PMID- 17517470
TI  - Immunization with liposome-anchored pegylated peptides modulates doxorubicin
      sensitivity in P-glycoprotein-expressing P388 cells.
AB  - The clinical use of chemotherapy in cancer treatment is limited by the occurrence
      of multidrug resistance (MDR) associated with the overexpression of membrane
      transporters, one of the best known is P-glycoprotein (Pgp), that actively expels
      drugs out of tumor cells. To overcome Pgp-mediated MDR, synthetic peptides
      corresponding to fragments from extracellular loops 1, 2 and 4 of the murine Pgp
      were coupled to polyethylene glycol-distearoylphosphatidylethanolamine and
      inserted into empty or monophosphoryl lipid A-containing liposomes. This
      formulation elicited specific antibodies which blocked Pgp-mediated efflux of
      doxorubicin, resulting in increased intracellular drug accumulation and
      subsequent potentiation of the cytotoxic effect of doxorubicin on multidrug
      resistant P388 (P388R) cells. Previous immunizations with MDR1 peptides improved
      the efficiency of chemotherapy against P388R cells in vivo, with an increase of
      83% of mice survival time. Overall, these results suggest that this approach can
      modulate Pgp activity by blocking drug efflux and may have clinical relevance as
      an alternative strategy to toxic chemosensitizers in drug-resistant cancer
      therapy.

PMID- 17517471
TI  - Decomposition kinetics of ammonia in gaseous stream by a nanoscale copper-cerium
      bimetallic catalyst.
AB  - This study performance is to examine the kinetics over nanoscale copper-cerium
      bimetallic catalyst under selective catalytic oxidation (SCO) of ammonia to N(2)
      in a tubular fixed-bed reactor (TFBR) at temperatures from 150 to 400 degrees C
      in the presence of oxygen. The nanoscale copper-cerium bimetallic catalyst was
      prepared by co-precipitation with Cu(NO(3))(2) and Ce(NO(3))(3) at molar ratio of
      6:4. Experimental results showed that the catalyst with transmission electron
      microscopy (TEM) revealed that copper and cerium are well dispersed and catalyst
      in the form of nanometer-sized particles. Moreover, the kinetic behavior of NH(3)
      oxidation with catalysis can be accounted by using the rate expression of the
      Langmuir-Hinshelwood type kinetic model. Kinetic parameters are also developed on
      the basis of the differential reactor data. Also, experimental results are
      compared with those of the model predicted.

PMID- 17517472
TI  - Investigation of bromide ion effects on disinfection by-products formation and
      speciation in an Istanbul water supply.
AB  - Recent epidemiological studies reported that brominated DBPs may be more
      carcinogenic than their chlorinated analogs. Thus, this research was designed to
      investigate the role of bromide ion in the formation and speciation of
      disinfection by-products (DBPs) during chlorination of Buyukcekmece Lake Water
      (BLW) in Istanbul. Chlorination of BLW samples was carried out at pH 7.0 with 5
      and 12 mg/l chlorine dosages. For each chlorine dosage, six bromide
      concentrations ranging from 0.05 to 4.0mg/l were added to form a 2 x 6
      experimental matrix. In general, increasing bromide concentration gradually
      shifted trihalomethanes (THMs) and haloacetic acids (HAAs) speciation from
      chlorinated species to the mixed bromochloro species during chlorination. The
      halogen substitution ability of HOBr and HOCl during the formation of THMs and
      HAAs can be estimated through the use of probability theory. It was concluded
      that, in both halogen substitution for THM and dihalogenated HAA formation, HOBr
      was found to be 20 times more reactive than HOCl.

PMID- 17517473
TI  - Neuronal somatic volume of posteroventral medial amygdala cells from males and
      across the estrous cycle of female rats.
AB  - The posteroventral medial amygdala (MePV) is a brain area where gonadal hormones
      have neurotrophic effects in rats. The aim of the present study was to estimate
      the MePV neuronal somatic volume from males and diestrus, proestrus and estrus
      female Wistar rats (n=5 in each group) in an attempt to identify a possible
      sexual dimorphism in this parameter. The effect of laterality was also evaluated.
      The brains of adult animals were sectioned (1 microm), stained with 1% toluidine
      blue and serial-section reconstructions of each neuronal cell body were obtained.
      Images from both left and right MePV were studied and the somatic volume was
      estimated using the Cavalieri method in combination with the point counting
      technique. Results were compared according to sex and phase of the estrous cycle
      using a two-way ANOVA for repeated measures followed by the least significance
      difference test. Mean neuronal somatic volume showed a statistical difference
      among groups and the post hoc comparisons revealed that males present higher
      values than females in proestrus and estrus (p<0.05). On the other hand, neither
      a laterality effect (p=0.6) nor an interaction between groups and laterality
      (p=0.4) were found. Our results indicate that cell body volume in the MePV is
      distinct when comparing males to females in the different phases of the estrous
      cycle. Through dynamic changes modulated by sex steroids, it is likely that this
      morphological plasticity within the MePV may be affecting the functioning of
      local neurons and their integrated roles in neural circuits relevant for
      neuroendocrine control and reproductive behaviors.

PMID- 17517474
TI  - One day at a time: The impact of daily satisfaction with spouse responses on
      pain, negative affect and catastrophizing among individuals with rheumatoid
      arthritis.
AB  - The majority of research on pain catastrophizing has focused on its negative
      consequences for adjustment to chronic pain, with few investigations of factors
      that influence catastrophizing or its detrimental effects. Using a daily process
      methodology, the current study examined, first, the extent to which a supportive
      social environment plays a role in reduced catastrophizing, and second, the
      extent to which support might protect against the detrimental effects of
      catastrophizing on well-being. Sixty-nine married individuals with rheumatoid
      arthritis took part in an initial background interview, followed by twice daily
      telephone interviews (regarding pain intensity, negative affect, catastrophizing
      and satisfaction with spouse responses) for 1 week. Multi-level modeling
      indicated several pathways through which satisfaction with spouse responses
      disrupts the vicious cycle of pain, negative affect and catastrophizing.
      Consistent with past research, catastrophizing was associated with increases in
      pain and negative affect. However, when individuals reported increases in
      satisfaction with spouse responses they were less likely to experience increases
      in negative affect due to catastrophizing. Satisfaction with spouse responses
      also reduced the likelihood of feeling overwhelmed and helpless in dealing with
      daily pain. The relationship between pain and catastrophizing was attenuated in
      the context of increases in satisfaction with spouse responses. Negative affect
      was associated with increases in catastrophizing, but only when individuals
      reported decreases in satisfaction with spouse responses. Overall, findings were
      consistent with a model in which satisfaction with spouse responses serves as a
      coping resource, and suggests the importance of involving close others in
      treatments to reduce pain and catastrophizing.

PMID- 17517475
TI  - Antinociceptive effect and interaction of uncompetitive and competitive NMDA
      receptor antagonists upon capsaicin and paw pressure testing in normal and
      monoarthritic rats.
AB  - We assessed whether intrathecal administration of the uncompetitive and
      competitive NMDA receptor antagonists ketamine and (+/-)CPP, respectively, could
      produce differential modulation on chemical and mechanical nociception in normal
      and monoarthritic rats. In addition, the antinociceptive interaction of ketamine
      and (+/-)CPP on monoarthritic pain was also studied using isobolographic
      analysis. Monoarthritis was produced by intra-articular injection of complete
      Freund's adjuvant into the tibio-tarsal joint. Four weeks later, the
      antinociceptive effect of intrathecal administration of the drugs alone or
      combined was evaluated by using the intraplantar capsaicin and the paw pressure
      tests. Ketamine (0.1, 1, 10, 30, 100, 300 and 1000 microg i.t.) and (+/-)CPP
      (0.125, 2.5, 7.5, 12.5, 25 and 50 microg i.t.) produced significantly greater
      dose-dependent antinociception in the capsaicin than in the paw pressure test.
      Irrespective of the nociceptive test employed, both antagonists showed greater
      antinociceptive activity in monoarthritic than in healthy rats. Combinations
      produced synergy of a supra-additive nature in the capsaicin test, but only
      additive antinociception in paw pressure testing. The efficacy of the drugs,
      alone or combined, is likely to depend on the differential sensitivity of tonic
      versus phasic pain and/or chemical versus mechanical pain to NMDA antagonists.

PMID- 17517476
TI  - LACDIF, a new electron diffraction technique obtained with the LACBED
      configuration and a C(s) corrector: comparison with electron precession.
AB  - By combining the large-angle convergent-beam electron diffraction (LACBED)
      configuration together with a microscope equipped with a C(s) corrector it is
      possible to obtain good quality spot patterns in image mode and not in
      diffraction mode as it is usually the case. These patterns have two main
      advantages with respect to the conventional selected-area electron diffraction
      (SAED) or microdiffraction patterns. They display a much larger number of
      reflections and the diffracted intensity is the integrated intensity. These
      patterns have strong similarities with the electron precession patterns and they
      can be used for various applications like the identification of the possible
      space groups of a crystal from observations of the Laue zones or the ab-initio
      structure identifications. Since this is a defocused method, another important
      application concerns the analysis of electron beam-sensitive materials.
      Successful applications to polymers are given in the present paper to prove the
      validity of this method with regards to these materials.

PMID- 17517477
TI  - Toxocara canis: proteinases in perivitelline fluid from hatching eggs.
AB  - Developing larvae of Toxocara canis may secrete several kinds of enzymes within
      the egg perivitelline fluid (EPF) prior to and during hatching. In particular,
      proteinases in EPF could play a role in larval emergence within the host
      gastrointestinal lumen but its presence and nature is unknown. In this work,
      proteolytic activities in hatching fluid of T. canis were identified and analysed
      by substrate gel electrophoresis at different pH values and by using type
      specific protease inhibitors. Three bands of 91, 68 and 38 kDa showed
      gelatinolytic activity and all proteinase activity from EPF was of the aspartic
      type since it was inhibited by pepstatin A. Interestingly, a significantly higher
      proteolytic activity was observed at acidic pH (< or =5.5). These data suggest
      that T. canis developmentally secretes and accumulates in EPF aspartic
      proteinases with a pH-dependent activity that might help the parasite to take
      advantage of conditions in the host gastrointestinal microenvironment where egg
      hatching is induced and executed.

PMID- 17517478
TI  - Long-term outcome and toxicities of intraoperative radiotherapy for high-risk
      neuroblastoma.
AB  - PURPOSE: To review a historical cohort of consecutively accrued patients with
      high-risk neuroblastoma treated with intraoperative radiotherapy (IORT) to
      determine the therapeutic effect and late complications of this treatment.
      METHODS AND MATERIALS: Between 1986 and 2002, 31 patients with newly diagnosed
      high-risk neuroblastoma were treated with IORT as part of multimodality therapy.
      Their medical records were reviewed to determine the outcome and complications.
      Kaplan-Meier probability estimates of local control, progression-free survival,
      and overall survival at 36 months after diagnosis were recorded. RESULTS:
      Intraoperative radiotherapy to the primary site and associated lymph nodes
      achieved excellent local control at a median follow-up of 44 months. The 3-year
      estimate of the local recurrence rate was 15%, less than that of most previously
      published series. Only 1 of 22 patients who had undergone gross total resection
      developed recurrence at the primary tumor site. The 3-year estimate of local
      control, progression-free survival, and overall survival was 85%, 47%, and 60%,
      respectively. Side effects attributable to either the disease process or
      multimodality treatment were observed in 7 patients who developed either
      hypertension or vascular stenosis. These late complications resulted in the death
      of 2 patients. CONCLUSIONS: Intraoperative radiotherapy at the time of primary
      resection offers effective local control in patients with high-risk
      neuroblastoma. Compared with historical controls, IORT achieved comparable
      control and survival rates while avoiding many side effects associated with
      external beam radiotherapy in young children. Although complications were
      observed, additional analysis is needed to determine the relative contributions
      of the disease process and specific components of the multimodality treatment to
      these adverse events.

PMID- 17517479
TI  - Possession of ATM sequence variants as predictor for late normal tissue responses
      in breast cancer patients treated with radiotherapy.
AB  - PURPOSE: The ATM gene product is a central component of cell cycle regulation and
      genomic surveillance. We hypothesized that DNA sequence alterations in ATM
      predict for adverse effects after external beam radiotherapy for early breast
      cancer. METHODS AND MATERIALS: A total of 131 patients with a minimum of 2 years
      follow-up who had undergone breast-conserving surgery and adjuvant radiotherapy
      were screened for sequence alterations in ATM using DNA from blood lymphocytes.
      Genetic variants were identified using denaturing high performance liquid
      chromatography. The Radiation Therapy Oncology Group late morbidity scoring
      schemes for skin and subcutaneous tissues were applied to quantify the radiation
      induced effects. RESULTS: Of the 131 patients, 51 possessed ATM sequence
      alterations located within exons or in short intron regions flanking each exon
      that encompass putative splice site regions. Of these 51 patients, 21 (41%)
      exhibited a minimum of a Grade 2 late radiation response. In contrast, of the 80
      patients without an ATM sequence variation, only 18 (23%) had radiation-induced
      adverse responses, for an odds ratio of 2.4 (95% confidence interval, 1.1-5.2).
      Fifteen patients were heterozygous for the G-->A polymorphism at nucleotide 5557,
      which causes substitution of asparagine for aspartic acid at position 1853 of the
      ATM protein. Of these 15 patients, 8 (53%) exhibited a Grade 2-4 late response
      compared with 31 (27%) of the 116 patients without this alteration, for an odds
      ratio of 3.1 (95% confidence interval, 1.1-9.4). CONCLUSION: Sequence variants
      located in the ATM gene, in particular the 5557 G-->A polymorphism, may predict
      for late adverse radiation responses in breast cancer patients.

PMID- 17517480
TI  - Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained
      on 100mg of daily methadone.
AB  - RATIONALE: Acute doses of buprenorphine can precipitate withdrawal in opioid
      dependent persons. The likelihood of this withdrawal increases as a function of
      the level of physical dependence. OBJECTIVES: To test the acute effects of
      sublingual buprenorphine/naloxone tablets in volunteers with a higher level of
      physical dependence. The goal was to identify a dose that would precipitate
      withdrawal (Phase 1), then determine if withdrawal could be attenuated by
      splitting this dose (Phase 2). METHODS: Residential laboratory study; subjects
      (N=16) maintained on 100mg per day of methadone. Phase 1: randomized, double
      blind, triple dummy, within subject study. Conditions were sublingual
      buprenorphine/naloxone (4/1, 8/2, 16/4, 32mg/8mg), intramuscular naloxone
      (0.2mg), oral methadone (100mg), or placebo. Medication conditions were
      randomized, but buprenorphine/naloxone doses were ascending within the
      randomization. Phase 2: Conditions were methadone, placebo, naloxone, 100% of the
      buprenorphine/naloxone dose that precipitated withdrawal in Phase 1 (full dose),
      and 50% of this dose administered twice in a session (split dose). Analyses
      covaried by trough methadone serum levels. RESULTS: Six subjects did not complete
      the study. Of the 10 who completed, 3 tolerated up to 32mg/8mg of
      buprenorphine/naloxone without evidence of precipitated withdrawal. For the seven
      completing both phases, split doses generally produced less precipitated
      withdrawal compared to full doses. CONCLUSIONS: There is considerable between
      subject variability in sensitivity to buprenorphine's antagonist effects. Low,
      repeated doses of buprenorphine/naloxone (e.g., 2mg/0.5mg) may be an effective
      mechanism for safely dosing this medication in persons with higher levels of
      physical dependence.

PMID- 17517481
TI  - Phenotypic and genotypic characterization of Paenibacillus larvae isolates.
AB  - Paenibacillus larvae is the causative agent of American Foulbrood (AFB), a severe
      disease of honeybees (Apis melifera). The aim of this work was to develop a
      strategy for the subtyping and the epidemiological analysis of P. larvae.
      Phenotypic characterisation, susceptibility to several antibiotics,
      electrophoresis of whole bacterial proteins, rep-PCR, ribotyping and DGGE were
      assessed using a collection of P. larvae isolates from different Uruguayan and
      Argentinean locations. Results indicated that there are two P. larvae genotypes
      circulating in Uruguay ERIC I-BOX A (worldwide distributed) and ERIC I-BOX C
      (exclusively detected in Argentina until this study). These results suggest that
      P. larvae isolates had moved between Argentina and Uruguay, probably through the
      Uruguay River. Patterns of whole bacterial proteins, DGGE and ribotyping did not
      improve the P. larvae intraspecific discrimination. Antibiotic susceptibility
      assays showed that 100% isolates were OTC-sensitive and 22% (belonging to ERIC I
      BOX A group) were sulfisoxazole-resistant. This work may contribute to the
      elucidation of basic aspects related to the epidemiology of AFB in Uruguay and in
      the region.

PMID- 17517482
TI  - A complex intersex condition in a Holstein calf.
AB  - A case of disrupted embryonic development of the genital tract in a newborn
      Holstein calf is described. The physical examination of the calf evidenced
      several abnormalities, like atresia ani, rudimentary external genitalia and
      caudal vertebral agenesis. On necropsy, the excised genitalia consisted of
      bilateral streak gonads, apparently normal uterine tubes, a fluid-filled uterus,
      a long vagina and a very narrow clitoris-like structure covered with a discrete
      skin-fold. The urinary tract seemed normal and the urethra's opening was at the
      vestibule-vaginal junction. A cytogenetic analysis was requested. Karyotype
      revealed the existence of Y chromosome material in the two X chromosomes.
      However, the search for the sex-determining region Y (SRY) showed that this was
      an apparently absent gene. The histological examination of the gonads revealed
      the existence of ovarian dysplasia. Uterine sections evidenced the absence of the
      uterine epithelium, with only sporadic caruncles. Under microscopic examination,
      the uterine tubes and vagina structure was normal. The external genitalia
      sections revealed the existence of a skin-fold covering an erectile structure
      surrounding the urethra, a structure more similar to a penis than to a clitoris.
      This is an unusual situation of gonadal dysplasia combined with genital tract
      anomalies in cattle, probably associated to a genetic defect.

PMID- 17517483
TI  - In vitro and in vivo study of poly(ethylene glycol) conjugated ketoprofen to
      extend the duration of action.
AB  - Ketoprofen-polyethylene glycol (PEG) conjugates (KPEG) were prepared and their
      potential as a prolonged release system was investigated. Three KPEG conjugates
      were synthesized from ketoprofen and methoxy PEG with three different molecular
      weights by esterification in the presence of DCC. The KPEG conjugates were
      characterized by FT-IR and (1)H NMR spectroscopy. The rate of hydrolysis profile
      showed a specific acid-base catalysis pattern with a minimum at pH 4-5. The
      pharmacokinetic study after the intravenous and intramuscular administration of
      KPEG750 showed that the plasma levels of KP increased slowly and reached a
      maximum concentration at later time. The AUC of KPEG750 was higher than that
      after administering an equivalent dose of ketoprofen except 40mg/kg dose of
      intramuscular administration. The tail-flick experiment and paw edema test after
      intramuscular administration showed that KPEG750 had extended analgesic and anti
      inflammatory effects compared with ketoprofen. These results suggest that KPEG
      could be a promising NSAID prodrug with an extended pharmacological effect owing
      to delayed-release of parent drug.

PMID- 17517484
TI  - Fixation and detachment of superior and anterior malleolar ligaments in human
      middle ear: experiment and modeling.
AB  - The aim of this study is to investigate the function of the superior malleolar
      ligament (SML) and the anterior malleolar ligament (AML) in human middle ear for
      sound transmission through simulations of fixation and detachment of these
      ligaments in human temporal bones and a finite element (FE) ear model. Two laser
      vibrometers were used to measure the vibrations of the tympanic membrane (TM) and
      stapes footplate. A 3-D FE ear model was used to predict the transfer function of
      the middle ear with ligament fixation and detachment. The results demonstrate
      that fixations and detachments of the SML and AML had different effects on TM and
      stapes footplate movements. Fixation of the SML resulted in a reduction of
      displacement of the TM (umbo) and the footplate at low frequencies (f<1000 Hz),
      but also caused a shift of displacement peak to higher frequencies. Fixation of
      both SML and AML caused a reduction of 15 dB at umbo or stapes at low
      frequencies. Detachment of the SML had almost no effect on TM and footplate
      mobility, but AML detachment had a minor effect on TM and footplate movement. The
      FE model was able to predict the effects of SML and AML fixation and detachment.

PMID- 17517485
TI  - Endovascular management performed percutaneously of isolated iliac artery
      aneurysms.
AB  - PURPOSE: To report about the endovascular treatment of isolated iliac artery
      aneurysms (IIAA) with stentgraft placement and transluminal or CT-guided
      embolization of the internal iliac artery or the combination of these methods.
      METHODS AND MATERIALS: Over a period of 5.6 years, 36 interventions were
      performed in 20 patients with 23 IIAAs. In a retrospective analysis patient
      records were reviewed. The CT-angiography follow-up was evaluated for the
      presence of re-perfusion of the IIAA and for change of aneurysm diameter.
      RESULTS: Primary success was achieved in 15/23 aneurysms (65%), and secondary
      success in 21/23 aneurysms (91%). In 5/23 cases two interventions and in 1/23
      cases three interventions were necessary to achieve secondary success.
      Embolization alone, as a therapy for aneurysms involving only the internal iliac
      artery, had a success rate of 27%. No procedure-related minor or major
      complications occurred. Mean decrease of aneurysm size during a mean observation
      period of 14.1 months was 6.9% which was not significant (p=0.3; 95% confidence
      interval +7-21%). CONCLUSION: Endovascular therapy of isolated iliac artery
      aneurysms performed percutaneously has become a treatment alternative to open
      surgical repair. This method is feasible and safe with low procedure-related
      morbidity and mortality. However, on average more than one intervention has to be
      performed to achieve successful permanent exclusion of the aneurysm and
      embolization alone in isolated internal iliac artery aneurysms is not sufficient.

PMID- 17517486
TI  - Investigating Hispanic/Latino perceptions about colorectal cancer screening: a
      community-based approach to effective message design.
AB  - OBJECTIVE: The Hispanic/Latino population has been documented as having the
      lowest colorectal cancer (CRC) screening rates in the United States, putting this
      group at-risk for late-stage presentation of disease. We assessed knowledge,
      attitudes, and behavior regarding CRC screening to inform the development of
      messages that promote screening among Hispanic/Latino patients. METHODS: In
      person structured interviews with Spanish-speaking adults age 50-80 at two
      clinics and a senior center in a Hispanic/Latino community (N=234). RESULTS: Most
      (67.1%) participants had no more than an eighth-grade education and 63.3%
      reported their reading ability as less than "very good." Only 18.4% of
      participants correctly identified the colon on a diagram; 19.2% correctly
      described at least one aspect of a polyp. Less than half of the participants
      perceived themselves as at-risk for CRC, and less than one-third knew about any
      of the standard screening tests. After hearing descriptions of the screening
      tests, participants perceived stool cards as easier, safer, less painful, less
      embarrassing, and less scary than endoscopy (p<.001). Approximately two-thirds of
      unscreened patients said that screening had never been mentioned or suggested to
      them; about one-quarter said they did not get screened because they felt fine or
      were not worried. Over 96% of participants said they would get screened if a
      doctor suggested it. CONCLUSION: Assessing knowledge, attitudes, beliefs, and
      experiences in the community of interest is a promising approach for developing
      effective targeted health messages. PRACTICE IMPLICATIONS: Messages to increase
      CRC screening knowledge and behavior in the Hispanic/Latino community should
      address risk factors, identify relevant anatomy, explain polyps and their
      asymptomatic presentation, and clearly describe options.

PMID- 17517487
TI  - An internet-based study on the relation between disgust sensitivity and
      emetophobia.
AB  - In the etiology of disgust-relevant psychopathology, such as emetophobia (fear of
      vomiting), two factors may be important: disgust propensity, i.e., how quickly
      the individual experiences disgust, and disgust sensitivity, i.e., how negatively
      does the individual evaluate this disgust experience [van Overveld, W. J. M., de
      Jong, P. J., Peters, M. L., Cavanagh, K., & Davey, G. C. L. (2006). Disgust
      propensity and disgust sensitivity: separate constructs that are differentially
      related to specific fears. Personality and Individual Differences, 41, 1241
      1252]. Hence, the current study examines whether emetophobic participants display
      elevated levels of disgust propensity and sensitivity, and whether these factors
      are differentially related to emetophobia. A group of emetophobic members of a
      Dutch website on emetophobia (n=172), and a control group (n=39) completed an
      internet survey containing the Emetophobia Questionnaire, Disgust Propensity and
      Sensitivity Scale-Revised, Disgust Scale, and Disgust Questionnaire. Results
      showed that the emetophobic group displayed significantly elevated levels of both
      disgust propensity and disgust sensitivity compared to the control group. Most
      importantly, disgust sensitivity consistently was the best predictor of
      emetophobic complaints.

PMID- 17517488
TI  - Autoimmune disease and innervation.
AB  - In the decades before 1987, most of the research devoted to neuronal innervation
      was carried out in primary and secondary lymphoid organs at very different
      locations. This was an important period in order to understand hard-wiring of
      immune organs in physiology. Between 1988 and 1997, with the appearance of
      specific antibodies against neuronal markers, innervation was studied in inflamed
      tissue of patients and of animals with autoimmune diseases. This period clearly
      revealed that nerve fibers of, both, the sympathetic and sensory nervous system
      are altered, but only small amounts of tissue have been investigated by
      qualitative but not quantitative techniques. Between 1998 and 2007, with the
      understanding that sympathetic and sensory neurotransmitters might play opposite
      roles in inflammation, nerve fibers of the different nervous systems have been
      studied in parallel using quantitative techniques. These studies have been
      carried out in a large number of patients with long-standing autoimmune diseases.
      It turned out that sympathetic nerve fibers are lost in chronically inflamed
      tissue, while substance P-positive nerve fibers sprout into the inflamed area.
      This might be important because high concentrations of sympathetic
      neurotransmitters are antiinflammatory whereas substance P has a proinflammatory
      role. The first challenge for future research is the determination of innervation
      in the early human autoimmune disease. The second challenge is the identification
      of reasons for the differential loss of sympathetic in relation to sensory nerve
      fibers. It might well be that nerve repellent factors specific for the
      sympathetic nerve fiber might play an important role for the observed
      differential loss. Whether, or not, a therapy can be based on these findings
      remains to be established.

PMID- 17517489
TI  - Edge of chaos and prediction of computational performance for neural circuit
      models.
AB  - We analyze in this article the significance of the edge of chaos for real-time
      computations in neural microcircuit models consisting of spiking neurons and
      dynamic synapses. We find that the edge of chaos predicts quite well those values
      of circuit parameters that yield maximal computational performance. But obviously
      it makes no prediction of their computational performance for other parameter
      values. Therefore, we propose a new method for predicting the computational
      performance of neural microcircuit models. The new measure estimates directly the
      kernel property and the generalization capability of a neural microcircuit. We
      validate the proposed measure by comparing its prediction with direct evaluations
      of the computational performance of various neural microcircuit models. The
      proposed method also allows us to quantify differences in the computational
      performance and generalization capability of neural circuits in different dynamic
      regimes (UP- and DOWN-states) that have been demonstrated through intracellular
      recordings in vivo.

PMID- 17517490
TI  - Decoupled echo state networks with lateral inhibition.
AB  - Building on some prior work, in this paper we describe a novel structure termed
      the decoupled echo state network (DESN) involving the use of lateral inhibition.
      Two low-complexity implementation schemes, namely, the DESN with reservoir
      prediction (DESN + RP) and DESN with maximum available information (DESN +
      MaxInfo), are developed: (1) In the multiple superimposed oscillator (MSO)
      problem, DESN + MaxInfo exhibits three important attributes: lower generalization
      mean-square error (MSE), better robustness with respect to the random generation
      of reservoir weight matrix and feedback connections, and robustness to variations
      in the sparseness of reservoir weight matrix, compared to DESN + RP. (2) For a
      noiseless nonlinear prediction task, DESN + RP outperforms the DESN + MaxInfo and
      single reservoir-based ESN approach in terms of lower prediction MSE and better
      robustness to a change in the number of inputs and sparsity of the reservoir
      weight matrix. Finally, in a real-life prediction task using noisy sea clutter
      data, both schemes exhibit higher prediction accuracy and successful design ratio
      than a conventional ESN with a single reservoir.

PMID- 17517491
TI  - Online reservoir adaptation by intrinsic plasticity for backpropagation
      decorrelation and echo state learning.
AB  - We propose to use a biologically motivated learning rule based on neural
      intrinsic plasticity to optimize reservoirs of analog neurons. This rule is based
      on an information maximization principle, it is local in time and space and thus
      computationally efficient. We show experimentally that it can drive the neurons'
      output activities to approximate exponential distributions. Thereby it implements
      sparse codes in the reservoir. Because of its incremental nature, the intrinsic
      plasticity learning is well suited for joint application with the online
      backpropagation-decorrelation or the least mean squares reservoir learning, whose
      performance can be strongly improved. We further show that classical echo state
      regression can also benefit from reservoirs, which are pre-trained on the given
      input signal with the implicit plasticity rule.

PMID- 17517492
TI  - An experimental unification of reservoir computing methods.
AB  - Three different uses of a recurrent neural network (RNN) as a reservoir that is
      not trained but instead read out by a simple external classification layer have
      been described in the literature: Liquid State Machines (LSMs), Echo State
      Networks (ESNs) and the Backpropagation Decorrelation (BPDC) learning rule.
      Individual descriptions of these techniques exist, but a overview is still
      lacking. Here, we present a series of experimental results that compares all
      three implementations, and draw conclusions about the relation between a broad
      range of reservoir parameters and network dynamics, memory, node complexity and
      performance on a variety of benchmark tests with different characteristics. Next,
      we introduce a new measure for the reservoir dynamics based on Lyapunov
      exponents. Unlike previous measures in the literature, this measure is dependent
      on the dynamics of the reservoir in response to the inputs, and in the cases we
      tried, it indicates an optimal value for the global scaling of the weight matrix,
      irrespective of the standard measures. We also describe the Reservoir Computing
      Toolbox that was used for these experiments, which implements all the types of
      Reservoir Computing and allows the easy simulation of a wide range of reservoir
      topologies for a number of benchmarks.

PMID- 17517493
TI  - Fast neural network surrogates for very high dimensional physics-based models in
      computational oceanography.
AB  - We present neural network surrogates that provide extremely fast and accurate
      emulation of a large-scale circulation model for the coupled Columbia River, its
      estuary and near ocean regions. The circulation model has O(10(7)) degrees of
      freedom, is highly nonlinear and is driven by ocean, atmospheric and river
      influences at its boundaries. The surrogates provide accurate emulation of the
      full circulation code and run over 1000 times faster. Such fast dynamic
      surrogates will enable significant advances in ensemble forecasts in oceanography
      and weather.

PMID- 17517494
TI  - The cerebellum as a liquid state machine.
AB  - We examined closely the cerebellar circuit model that we have proposed
      previously. The model granular layer generates a finite but very long sequence of
      active neuron populations without recurrence, which is able to represent the
      passage of time. For all the possible binary patterns fed into mossy fibres, the
      circuit generates the same number of different sequences of active neuron
      populations. Model Purkinje cells that receive parallel fiber inputs from neurons
      in the granular layer learn to stop eliciting spikes at the timing instructed by
      the arrival of signals from the inferior olive. These functional roles of the
      granular layer and Purkinje cells are regarded as a liquid state generator and
      readout neurons, respectively. Thus, the cerebellum that has been considered to
      date as a biological counterpart of a perceptron is reinterpreted to be a liquid
      state machine that possesses powerful information processing capability more than
      a perceptron.

PMID- 17517495
TI  - Optimization and applications of echo state networks with leaky-integrator
      neurons.
AB  - Standard echo state networks (ESNs) are built from simple additive units with a
      sigmoid activation function. Here we investigate ESNs whose reservoir units are
      leaky integrator units. Units of this type have individual state dynamics, which
      can be exploited in various ways to accommodate the network to the temporal
      characteristics of a learning task. We present stability conditions, introduce
      and investigate a stochastic gradient descent method for the optimization of the
      global learning parameters (input and output feedback scalings, leaking rate,
      spectral radius) and demonstrate the usefulness of leaky-integrator ESNs for (i)
      learning very slow dynamic systems and replaying the learnt system at different
      speeds, (ii) classifying relatively slow and noisy time series (the Japanese
      Vowel dataset--here we obtain a zero test error rate), and (iii) recognizing
      strongly time-warped dynamic patterns.

PMID- 17517496
TI  - Metastatic melanoma of the gallbladder.
AB  - We report the findings of a magnetic resonance (MR) imaging analysis of
      metastatic melanoma of the gallbladder in a 36-year-old woman. MR imaging
      revealed that the gallbladder wall was diffusely thickened, and the tumor showed
      slightly high-intensity on T1-weighted images. The apparent diffusion coefficient
      value of the tumor was 0.69 x 10(-3)mm(2)/s, indicating high cellularity.
      Surgical specimens revealed that the tumor was a metastatic melanoma showing
      medullary growth with intratumoral hemorrhaging. These MR findings are helpful
      for preoperative diagnosis.

PMID- 17517497
TI  - Three-dimensional finite elemental analysis of zygomatic implants in craniofacial
      structures.
AB  - The objective of this study was to analyse stress distribution in craniofacial
      structures around zygomatic osseointegrated implants. An integrated system for
      Digital Imaging and Communications in Medicine (DICOM) data were utilized to
      create a three-dimensional model of craniofacial structures. The amount and
      distribution of the main stresses were compared using three-dimensional finite
      elemental analysis. The system allowed visual confirmation and analysis of stress
      distribution as well as the convenient and simple construction of a digital
      biomechanical model that provided details of anatomical structures in the regions
      of interest. Zygomatic implants with or without connected implants supporting the
      superstructure were compared. Stresses in severely resorbed maxillae with
      connected implants were not concentrated around the alveolar bone supporting the
      zygomatic implants. Stresses where there were no connected implants tended to be
      generated in the zygomatic bone, at the middle part of the zygomatic implant and
      at the joint of the fixture-abutment. Stress due to occlusal forces is mainly
      supported by the zygomatic bone, is transferred predominantly through the
      infrazygomatic crest, and is divided between the frontal and temporal processes
      of the zygomatic bone in different directions.

PMID- 17517498
TI  - Role of ATP-sensitive potassium channels in the biphasic effects of morphine on
      pentylenetetrazole-induced seizure threshold in mice.
AB  - Although several studies have indicated that the opioid receptor agonist morphine
      exerts biphasic effects on clonic seizure threshold, as yet little is known of
      the underlying mechanisms in this effect. In the present study, using the
      specific ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide and the
      specific K(ATP) channel opener cromakalim, the possible involvement of K(ATP)
      channels in the effects of morphine on pentylenetetrazole (PTZ)-induced seizure
      threshold in mice was investigated. Acute administration of lower doses of
      morphine (1, 3 and 7.5 mg/kg, i.p.) increased and higher doses of morphine (30
      and 60 mg/kg, i.p.) decreased the PTZ-induced seizure threshold. Glibenclamide
      (2.5-5 mg/kg) increased the PTZ-induced seizure threshold. Non-effective dose of
      cromakalim (0.1 microg/kg) inhibited anticonvulsant effect of glibenclamide (5
      mg/kg). Acute administration of non-effective dose of glibenclamide (1 mg/kg)
      interestingly inhibited both anticonvulsant and pro-convulsant effects of
      morphine and this effect was significantly reversed by cromakalim (0.1
      microg/kg). These results support the involvement of K(ATP) channels in the
      modulation of seizure threshold by morphine.

PMID- 17517499
TI  - Impulsivity in bipolar-II disorder: trait, state, or both?
AB  - BACKGROUND: In bipolar-II (BP-II) disorder impulsivity (defined as excessive
      risky activities by DSM-IV-TR) is one of the symptoms of hypomania. It is unclear
      if impulsivity is also a trait in BP-II. STUDY AIM: The aim was to test if
      impulsivity was also a trait in BP-II. METHODS: Consecutive 136 remitted BP-II
      outpatients (assessed when presenting for depression by a mood disorder
      specialist psychiatrist using the Structured Clinical Interview for DSM-IV), self
      assessed trait impulsivity during follow-ups, using the Personality Questionnaire
      of the Structured Clinical Interview for DSM-IV Axis II Disorders, in a private
      practice. Trait mood swings were also self-assessed, using the TEMPS-A. A trait
      nature of impulsivity in BP-II could be supported by finding (1) a relatively
      high frequency, (2) association between trait impulsivity and symptoms of past
      hypomania, especially impulsivity, (3) dose-response relationship between number
      of past hypomania symptoms and trait impulsivity, and (4) association between
      trait impulsivity and trait mood swings (a trait feature of BP-II). RESULTS:
      Trait impulsivity was present in 41.1% of BP-II. BP-II with, versus BP-II
      without, trait impulsivity had significantly more males, trait mood swings, past
      hypomania symptoms (irritable mood, talkativeness, increased goal-directed
      activity), and excessive risky activities (i.e. state impulsivity), corresponding
      to an irritable risky overactivity. Past state impulsivity and trait impulsivity
      were significantly associated. Number of past hypomania symptoms and trait
      impulsivity were significantly correlated. A dose-response relationship was found
      between number of past hypomania symptoms and trait impulsivity. DISCUSSION:
      Findings suggest that trait impulsivity may be a feature of BP-II. Limitation of
      self-assessment of personality traits should be taken into account. Findings may
      have treatment impacts, as the combination of trait impulsivity and mood swings
      may facilitate relapses and mixed states, which mood stabilising agents could
      prevent/delay.

PMID- 17517500
TI  - A comparison of Hickman line- and Port-a-Cath-associated complications in
      patients with solid tumours undergoing chemotherapy.
AB  - AIMS: To compare the complication rates of Hickman lines and Port-a-Caths in
      patients undergoing infusional chemotherapy for solid tumours. MATERIALS AND
      METHODS: A single institution retrospective analysis comparing complication rates
      for 30 Hickman lines and 33 Port-a-Caths inserted for chemotherapy in adults with
      solid tumours was carried out. RESULTS: Patients were well matched in terms of
      primary site and chemotherapy regimen. In both cases, over 85% were inserted
      radiologically under local anaesthetic. The total time in situ for Hickman lines
      and Port-a-Caths was 3539 days (median 83, range 6-585) and 5783 days (median
      158, range 20-456), respectively. The complication rate for Hickman lines was
      5.09/1000 catheter days, almost five times that for Port-a-Caths, with 1.04/1000
      catheter days, a relative risk of 4.9 (confidence interval: 1.9-15.1, P=0.0003).
      Most (73%) complications occurred within 4 weeks of insertion. However, some
      arose much later: the range of time to complication was 1-304 days for Hickman
      lines and 1-132 days for Port-a-Caths. Infection was the most common
      complication, accounting for nine of 18 Hickman line complications and five of
      six Port-a-Cath complications, giving an overall infection rate of 2.54/1000
      catheter days and 0.86/1000 catheter days, respectively. Additionally, Hickman
      lines had a 26% leakage rate or displacement rate, which did not occur at all in
      the Port-a-Cath group. Complications required the removal of 16 Hickman lines and
      five Port-a-Caths. The rate of removal was five times higher for Hickman lines
      (Hickman lines=4.52/1000 catheter days, Port-a-Caths=0.86/1000 catheter days,
      P=0.0027). Overall, the cost of Port-a-Caths was less than that of Hickman lines.
      CONCLUSION: In this study, Port-a-Caths were shown to be both safer and cheaper
      than Hickman lines for patients requiring infusional chemotherapy.

PMID- 17517501
TI  - Mycobacterium avium subspecies paratuberculosis diagnosis and geno-typing:
      genomic insights.
AB  - Effective control of paratuberculosis and investigations of potential link to
      Crohn's disease have been hampered by the lack of effective assays for easy and
      accurate diagnosis of Mycobacterium avium subspecies paratuberculosis (Map). Map
      is extremely fastidious and depends on iron chelator (Mycobactin). Map strains
      from humans and sheep are very difficult to isolate and may require years to
      emerge. Therefore, small numbers of Map isolates have been maintained in
      available collections. This situation has limited the study of biodiversity of
      Map. Though, much is known about environmental and host factors that contribute
      to paratuberculosis disease, but little is known about bacterial genetic
      mechanism of infection. Diagnostic and strain typing markers still demand
      improvements. Complete genome sequence of Map K10 strain is available in public
      domain for comparative genomics with other mycobacteria and clinical isolates of
      Map. It is anticipated that the genome sequence will help in carrying molecular
      diagnosis and strain typing with respect to Map forward at rapid pace. This paper
      reviews the current diagnostic and strain typing markers, which may be useful in
      typing of clinical isolates in near future.

PMID- 17517502
TI  - Ginkgo biloba in dyslexia: a pilot study.
AB  - OBJECTIVES: The purpose of this study was to collect preliminary information on
      the possible efficacy and tolerability of EGb 761 standardized plant extract of
      Ginkgo biloba as a treatment of dyslexia in school-aged children. METHODS:
      Fifteen children (5-16 year old) with dyslexia participated in an open-label
      trial of EGb 761 given as a single morning dose of 80 mg. Standardized tests for
      dyslexia were administered at baseline and at the end of the study. RESULTS: All
      15 children completed the trial. The score of the standardized tests for dyslexia
      decreased. On the list of words the score decreased from mean 4.33 (SD=2.37) at
      baseline to 2.66 (SD=1.58) at the end of the study (p<0.01), on the list of non
      words from mean 3.39 (SD=1.5) at baseline to 2.26 (SD=0.92) at the end of the
      study (p<0.02) and on the reading piece from mean 3.52 (SD=2.11) to 2.13
      (SD=1.25); at the end of the study (p<0.05). At the end of the study 9 children
      did not perform below the -2 SD on the list of words and 7 on reading text and so
      they no longer fulfilled the DSM-IV-TR criteria for dyslexia. A brief period of
      headache was reported by the parents of two children. CONCLUSION: These data
      suggest that EGb 761 standardized plant extract of Ginkgo biloba has acceptable
      acute tolerability at single doses up to 80 mg/day and is possibly efficacious in
      decreasing dyslexia difficulties. The need for a double-blind trial is discussed
      by the authors.

PMID- 17517503
TI  - The role of synchronous procedures in the treatment of colorectal liver
      metastases.
AB  - Twenty-five percent of colorectal cancer patients present with synchronous
      disease in the bowel and liver. Traditionally, the primary cancer was resected
      and the patient re-staged some 3-4 months later. In the interim, the majority of
      oncology centres offered these patients chemotherapy. At re-staging, if
      conditions remained favourable, hepatic resection was considered. This treatment
      protocol was supported by the literature published in the 1990s. However, there
      have been many advances in aggressive multimodality care of patients with
      metastatic colorectal cancer and there are increasing reports of the benefits of
      synchronous resection for this population of patients.

PMID- 17517504
TI  - Inhibitory effect of 2-arylbenzofurans from Erythrina addisoniae on protein
      tyrosine phosphatase-1B.
AB  - Bioassay-guided fractionation of an EtOAc-soluble extract of the stem bark of
      Erythrina addisoniae (Leguminosae), using an in vitro PTP1B inhibitory assay,
      resulted in the isolation of three new (1-3) and three known (4-6) 2
      arylbenzofuran derivatives. The new compounds were identified as 2-[2',4'
      dihydroxy-3'-(3-methylbut-2-enyl)phenyl]-6-hydroxybenzofuran (1), 2-[2'-methoxy
      4'-hydroxy-5'-(3-methylbut-2-enyl)phenyl]-6-hydroxybenzofuran (2), and 2-(2'
      methoxy-4'-hydroxyphenyl)-5-(3-methylbut-2-enyl)-6-hydroxybenzofuran (3). The new
      2-arylbenzofurans 1-3 inhibited PTP1B activity with IC(50) values ranging from
      13.6+/-1.1 to 17.5+/-1.2 microM in vitro assay. On the basis of the data
      obtained, 2-arylbenzofurans with prenyl group may be considered as a new class of
      PTP1B inhibitors.

PMID- 17517505
TI  - Hypoxia-driven elimination of thiopurines from their nitrobenzyl prodrugs.
AB  - A novel bioreductive prodrug of 6-thioguanine, 2-amino-6-[2-(4-nitrophenyl)prop-2
      ylsulfanyl]-9H-purine, containing a gem-dimethyl thioether linkage, was
      synthesised and compared with its unsubstituted analogue. In A549 whole cell
      experiments hypoxia selective release of 6-thioguanine was observed with the
      substituted prodrug only.

PMID- 17517506
TI  - Synthesis and biological evaluation of (R)-N
      (diarylmethylthio/sulfinyl)ethyl/propyl-piperidine-3-carboxylic acid
      hydrochlorides as novel GABA uptake inhibitors.
AB  - A series of new (R)-1-(2-diarylmethylthio/sulfinyl)ethyl-piperidine-3-carboxylic
      acid hydrochlorides 5a-d/6a-d and (R)-1-(3-diarylmethylthio)propyl-piperidine-3
      carboxylic acid hydrochlorides 5'a-d were synthesized and evaluated as gamma
      aminobutyric acid uptake inhibitors through cultured cell lines expressing mouse
      GAT1. Biological screening results demonstrated that the compounds 6a-d with
      diarylmethylsulfinyl ethyl side chain show more potent GAT1 inhibitory activities
      than 5a-d/5'a-d with diarylmethylthio ethyl/propyl moieties. Some of them, such
      as 6a, exhibited excellent inhibitions of [(3)H]-GABA uptake in cultured cells,
      which is 496-fold higher than (R)-nipecotic acid and 11.5 times less than
      tiagabine. The synthesis and structure-activity relationships are discussed.

PMID- 17517507
TI  - (Phenylpiperidinyl)cyclohexylsulfonamides: development of alpha1a/1d-selective
      adrenergic receptor antagonists for the treatment of benign prostatic
      hyperplasia/lower urinary tract symptoms (BPH/LUTS).
AB  - Although alpha(1) adrenergic receptor blockers can be very effective for the
      treatment of benign prostatic hyperplasia/lower urinary tract symptoms
      (BPH/LUTS), their usage is limited by CV-related side-effects that are caused by
      the subtype non-selective nature of the current drugs. To overcome this problem,
      it was hypothesized that a alpha(1a/1d) subtype selective antagonist would bring
      more benefit for the therapy of BPH/LUTS. In developing such selective
      alpha(1a/1d) ligands, a series of (phenylpiperidinyl)cyclohexylsulfonamides has
      been synthesized and evaluated for binding to three cloned human alpha(1)
      adrenergic receptor subtypes. Many compounds showed equal affinity for both
      alpha(1a) and alpha(1d) subtypes with good selectivity versus the alpha(1b)
      subtype.

PMID- 17517508
TI  - Photodynamic activity of water-soluble phthalocyanine zinc(II) complexes against
      pathogenic microorganisms.
AB  - Photodynamic activity of tetrakis-(3-methylpyridyloxy)- and tetrakis-(4
      sulfophenoxy)-phthalocyanine zinc(II) toward the gram-positive Staphylococcus
      aureus, the gram-negative Pseudomonas aeruginosa, and the fungi Candida albicans
      was studied. The drug uptake dependency with an inverse behavior to the cell
      density was observed. The cationic photosensitizer completely inactivated S.
      aureus and C. albicans, and with 4 log10 P. aeruginosa. The photoinactivation at
      mild experimental conditions, such as drug dose of 1.5 microM and fluence of 50
      mW cm(-2) for 10 min irradiation time, was shown.

PMID- 17517509
TI  - Bivalent ligand approach on 4-[2-(3-methoxyphenyl)ethyl]-1-(2
      methoxyphenyl)piperazine: synthesis and binding affinities for 5-HT(7) and 5
      HT(1A) receptors.
AB  - We here report on the synthesis and binding properties at 5-HT(7) and 5-HT(1A)
      receptors of ligands 3-12, that were designed according to the 'bivalent ligand'
      approach. Two moieties of the 5-HT(7)/5-HT(1A) ligand 4-[2-(3
      methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1) were linked through their
      3-methoxy substituent by polymethylene chains of variable length, with the aim to
      increase the affinity for 5-HT(7) receptor and the selectivity over 5-HT(1A)
      receptors. In the best cases, the dimers showed affinities for 5-HT(7) receptors
      as high as the monomer with no improvement in selectivity. Some dimers displayed
      5-HT(1A) receptor affinities slightly higher than monomer 1.

PMID- 17517510
TI  - Synthesis and evaluation of homo-bivalent GnRHR ligands.
AB  - G protein coupled receptors (GPCRs) are important drug targets in pharmaceutical
      research. Traditionally, most research efforts have been devoted towards the
      design of small molecule agonists and antagonists. An interesting, yet poorly
      investigated class of GPCR modulators comprise the bivalent ligands, in which two
      receptor pharmacophores are incorporated. Here, we set out to develop a general
      strategy for the synthesis of bivalent compounds that are projected to bind to
      the human gonadotropin-releasing hormone receptor (GnRHR). Our results on the
      dimerisation of a known GnRHR antagonist, with as key step the Huisgen 1,3
      cycloaddition, and their ability to bind to and antagonize GnRH-induced GnRHR
      stimulation, are presented here.

PMID- 17517511
TI  - QSAR studies and pharmacophore identification for arylsubstituted
      cycloalkenecarboxylic acid methyl esters with affinity for the human dopamine
      transporter.
AB  - Data from a series of 29 monoamine transport inhibitors were used to generate 2D
      and 3D QSAR models for their binding affinity to the human dopamine transporter
      (hDAT). Among the inhibitors were many non-nitrogen containing compounds. The 2D
      QSAR analysis resulted in the equation -logK(i)=4.00-3.93E(LUMO)-0.67E(HOMO)
      3.24sigma(p), which predicted the importance of electron withdrawing groups in
      the aromatic moiety. However, the model failed to predict the observed poor
      binding of nitro-substituted compounds. In contrast, a derived 3D QSAR model was
      capable of predicting these more correctly.

PMID- 17517512
TI  - Synthesis and biological activity of new anti-inflammatory compounds containing
      the 1,4-benzodioxine and/or pyrrole system.
AB  - A series of substituted derivatives containing the 1,4-benzodioxine or pyrrole
      nucleus are described. All the newly synthesized compounds were examined for
      their in vitro and in vivo anti-inflammatory activity. Several derivatives,
      including (S)-2, 14 and 17, showed more anti-inflammatory activity in vivo in
      these assays (rat paw oedema induced by carrageenan) than the known classical
      anti-inflammatory agent ibuprofen, whereas other compounds like 1 were equipotent
      to ibuprofen. Compound 17 was the most outstanding derivative because of its
      remarkable in vivo anti-inflammatory activity. In this paper, we examine and
      discuss the structure-activity relationships and anti-inflammatory activities of
      these compounds.

PMID- 17517513
TI  - Exploring DNA topoisomerase I inhibition by the benzo[c]phenanthridines
      fagaronine and ethoxidine using steered molecular dynamics.
AB  - The benzo[c]phenanthridines (BCPs) are a group of compounds that are believed to
      express their antitumor activity through the inhibition of topoisomerase I. The
      enzyme is crucial to cell cycle division and progression, and regulates the
      equilibrium between relaxed and supercoiled DNA that occurs during DNA
      replication. Over the years, we have prepared a number of BCPs and employed a
      number of biophysical techniques to explore their mechanism of action and improve
      their activity against this particular enzyme. The naturally occurring alkaloid
      fagaronine 1 and the synthetic compound ethoxidine 3 are two of the most active
      compounds, although their inhibitory mechanisms are different, being a poison and
      suppressor, respectively. We have modified the approach of steered molecular
      dynamics to create a torque on the intercalator to comprehensively sample the DNA
      binding site, and using topoisomerase I crystal structures, have proposed a model
      to explain the different mechanisms of action for these two BCP compounds.

PMID- 17517514
TI  - 7-Arylpiperazinylalkyl and 7-tetrahydroisoquinolinylalkyl derivatives of 8-alkoxy
      purine-2,6-dione and some of their purine-2,6,8-trione analogs as 5-HT(1A), 5
      HT(2A), and 5-HT(7) serotonin receptor ligands.
AB  - On the basis of our earlier studies with the serotonin receptor ligands in the
      group of 1,3-dimethyl-3,7-dihydropurine-2,6-dione derivatives, a series of new
      arylpiperazinylalkyl and tetrahydroisoquinolinylalkyl analogs of 8-alkoxy-1,3
      dimethyl-3,7-dihydropurine-2,6-dione (10-25) and 1,3-dimethyl-7,9-dihydro-3H
      purine-2,6,8-trione (26-30) were synthesized and their 5-HT(1A), 5-HT(2A), and 5
      HT(7) receptor affinities were determined. The new compounds 17, 18, 20, and 21
      were found to be highly active 5-HT(1A) receptor ligands (K(i)=11-19nM) with
      diversified affinity for 5-HT(2A) receptors (K(i)=15-253nM). Compounds 12, 13,
      15, and 19 were moderately potent 5-HT(2A) ligands (K(i)=23-57nM), whereas 17,
      18, 24, and 25 showed distinct affinity for 5-HT(7) receptors (K(i)=51-83nM).
      Purine-2,6,8-triones showed weak affinities for 5-HT(1A) and 5-HT(7) receptors;
      among them, 27 and 29 were classified as 5-HT(2A) receptor ligands. The selected
      compounds 17 and 21 were pharmacologically evaluated to determine their
      functional activities at pre-(hypothermia in mice) and post-(lower lip retraction
      in rats) synaptic 5-HT(1A) receptors. Compound 17 showed features of a potential
      agonist of pre- and post-synaptic 5-HT(1A) receptors, whereas 21 was classified
      as a potential, weak partial agonist of postsynaptic sites. Last of all, the most
      interesting compound 17 tested in behavioral models showed potential anxiolytic
      and antidepressant activities.

PMID- 17517515
TI  - Macro and microsurface morphology reconstructions during laser-induced etching of
      silicon.
AB  - Surface morphologies of the laser-etched silicon were studied as a function of
      the laser power densities. Scanning electron microscope (SEM) results show that
      different kind of microstructures develop. Pores like structures are formed at
      low laser power density and pillar like structures are obtained at higher laser
      power density. It is the etching rate, which is responsible for the surface
      morphology reconstructions. Etching rate was found to be a function of the laser
      power density. Atomic force microscope (AFM) results reveal that macro and
      microsurface morphology reconstructions take place simultaneously as a result of
      increasing etching rate. Macrosurface morphology reconstruction takes place on
      the silicon wafer surface and the microsurface morphology reconstruction takes
      place inside the pore wall.

PMID- 17517516
TI  - Radiosynthesis of 2'-deoxy-2'-[18F]-fluoro-5-methyl-1-beta-L
      arabinofuranosyluracil ([18F]-L-FMAU) for PET.
AB  - Radiosynthesis of 2'-deoxy-2'-[(18)F]-fluoro-5-methyl-1-beta-L
      arabinofuranosyluracil ([(18)F]-L-FMAU) is reported. Compound 1 was synthesized
      and converted to 2-triflate 2. Compound 3 was prepared from 2 using
      tetrabutylammonium[(18)F]fluoride, converted to 4, and then coupled with 5. The
      crude product was hydrolyzed, and purified by HPLC to obtain 7a. The
      radiochemical yield of [(18)F]-L-FMAU was 26% decay corrected (d.c.) in four runs
      with radiochemical purity >99% and specific activity 2200 mCi/micromol. The
      synthesis time was 3.3-3.5h from the end of bombardment (EOB).

PMID- 17517517
TI  - Can spontaneous pneumothorax patients be treated by ambulatory care management?
      Revisited.

PMID- 17517518
TI  - Presentation and outcome of Marfan's syndrome patients with dissection and
      thoraco-abdominal aortic aneurysm.
AB  - BACKGROUND: In Marfan's syndrome, there is a paucity of data regarding
      intervention criteria for surgery of the dissected thoraco-abdominal aorta.
      METHODS: A retrospective analysis of 22 Marfan's patients with distal aortic
      dissection managed between September 1999 and April 2006 was performed. Serial
      diameters and linear expansion rates were calculated from imaging studies and the
      outcome of intervention was analysed. RESULTS: There were 14/22 male patients
      (median age 38 years), and 18 had prior aortic surgery. Surgery was recommended
      in 20 patients and undertaken in 19 (1 died prior to operation). Of the operated
      patients, 2 presented with rupture, 2 with airway obstruction, 1 with
      intermittent paraplegia and 14 underwent planned surgery for increased expansion
      rate or pain. All patients had residual type A or chronic type B dissection. The
      median aortic dimension at surgery was 6.7 cm (interquartile range (IQR) 5.5
      8.2). The preoperative mean expansion rate increased from 0.5 cm/year to 1.7
      cm/year (p<0.001), prior to operation. Fifteen patients underwent Crawford Extent
      II, two underwent Extent I and two underwent Extent III repair. Profound
      hypothermia and CSF drainage was used in 16 and 18 patients, respectively. There
      was no early mortality, paraplegia or renal failure. At a median postoperative
      follow-up of 56 months (range 6-86), the survival of the operated cohort was 90%.
      CONCLUSIONS: Thoraco-abdominal aortic aneurysm repair in Marfan's syndrome can be
      performed with good outcomes. Intervention should be based on size or accelerated
      expansion. Any role of endovascular management needs careful consideration.

PMID- 17517520
TI  - Up-regulation of nerve growth factor and interleukin-10 in inflamed and non
      inflamed intestinal segments in rats with experimental colitis.
AB  - Inflammatory bowel diseases are characterized by dysregulated immune response to
      the normal microflora and structural and functional changes of the enteric
      nervous system which occur in inflamed as well as non-inflamed areas of the
      bowel. This study describes the changes in the expression of nerve growth factor
      (NGF) and interleukin-10 (IL-10) in the colon and in various segments of the
      small intestine in two rat models of experimental colitis induced by
      iodoacetamide or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Levels of NGF and IL
      10 were measured by ELISA in tissue homogenate sampled from duodenum, jejunum,
      ileum and colon at different time intervals. NGF and IL-10 increased
      significantly in homogenates of strips isolated from all small intestinal
      segments, 3-6h after iodoacetamide or TNBS administration and remained elevated
      until the colonic inflammation subsided. Similar but more pronounced increase
      occurred in areas of the colon adjacent to the ulcer. Histologic examinations
      revealed inflammatory changes in the colon; however, examination of sections from
      the small intestines did not reveal significant differences between controls and
      rats with colitis. The marked up-regulation of nerve growth factor and
      interleukin-10 in colitis suggests that they play a role in limiting or resolving
      inflammation and in preventing it from becoming uncontrolled. It also suggests
      that experimental colitis may be associated with latent inflammation in the small
      bowel.

PMID- 17517521
TI  - Virus inactivation by protein denaturants used in affinity chromatography.
AB  - Virus inactivation by a number of protein denaturants commonly used in gel
      affinity chromatography for protein elution and gel recycling has been
      investigated. The enveloped viruses Sindbis, herpes simplex-1 and vaccinia, and
      the non-enveloped virus polio-1 were effectively inactivated by 0.5 M sodium
      hydroxide, 6 M guanidinium thiocyanate, 8 M urea and 70% ethanol. However, pH
      2.6, 3 M sodium thiocyanate, 6 M guanidinium chloride and 20% ethanol, while
      effectively inactivating the enveloped viruses, did not inactivate polio-1. These
      studies demonstrate that protein denaturants are generally effective for virus
      inactivation but with the limitation that only some may inactivate non-enveloped
      viruses. The use of protein denaturants, together with virus reduction steps in
      the manufacturing process should ensure that viral cross contamination between
      manufacturing batches of therapeutic biological products is prevented and the
      safety of the product ensured.

PMID- 17517522
TI  - WHO technical workshop on stability of reference materials for biological
      medicines and in vitro diagnostics, Geneva, Switzerland, 28-29 November 2005.
AB  - In November 2005, the World Health Organization convened an informal technical
      workshop on the stability of reference materials for biological medicines and in
      vitro diagnostics. The meeting was attended by experts from WHO collaborating
      centres in the area of biological standardization, national control laboratories,
      industries and other relevant organizations. The consultation group discussed
      current practices and approaches to predicting and monitoring the stability of
      biological reference materials. The group agreed to the need for establishing a
      working group (i) to continue dialogue on potential issues encompassing the
      principles, strategies and practicality for assuring the stability of WHO
      international reference standards for biological medicines and in vitro
      diagnostics and (ii) to develop more detailed guidance for assessment of the
      stability of WHO international biological reference materials.

PMID- 17517523
TI  - Variations in articular calcified cartilage by site and exercise in the 18-month
      old equine distal metacarpal condyle.
AB  - OBJECTIVES: To interrelate articular calcified cartilage thickness,
      mineralisation density, tidemark count and tidemark linear accretion rate by site
      in the equine third metacarpal distal condyle. To determine the effects of
      exercise during early life on articular calcified cartilage. METHOD: Six of 12
      pasture-raised Thoroughbred horses were exercised from 10 days old. Calcein
      labels were given 19 and 8 days prior to euthanasia at 18 months old.
      Osteochondral specimens were cut from the distal third metacarpal condyle and
      imaged using confocal scanning light microscopy (CSLM) and quantitative
      backscattered electron scanning electron microscopy (qBSE). Articular calcified
      cartilage thickness and total thickness mineralisation density were measured on
      montaged qBSE image sets, and inter-label mineralisation density, tidemark count
      and linear accretion rate measured on registered CSLM-qBSE image pairs. RESULTS:
      Calcified cartilage thickness, mineralisation density, tidemark count and linear
      accretion rate varied significantly between sites. Regions with thinner calcified
      cartilage had greater linear accretion rates, hence rapid chondroclastic
      resorption. Mineralisation density was positively correlated with linear
      accretion rate. Fewer multiple tidemarks were counted in regions with greater
      linear accretion rates. Lag time between the tidemark and cement line was
      estimated (180 days; in the range of 0-648 days). Exercise had little effect on
      measured parameters. CONCLUSION: The major determinant of articular calcified
      cartilage thickness is the rate of chondroclastic resorption, not tidemark linear
      accretion rate. Our evidence supports coupled, mechanosensitive regulation of
      chondroclastic resorption and linear accretion rate in articular calcified
      cartilage. Exercising pasture-reared foals causes little additional adaptation in
      distal third metacarpal articular calcified cartilage.

PMID- 17517524
TI  - Effect of formaldehyde and resveratrol on the viability of Vero, HepG2 and MCF-7
      cells.
AB  - A non-transformed (Vero) and two tumor cell lines (HepG2 and MCF-7) were treated
      with 10nM to 100 microM formaldehyde. Lower doses (10nM to 10 microM) enhanced
      the viability of the cultured cells, measured by MTT assay. Higher doses (75-100
      microM) decreased viability of the cells by 50% or more. The 100 microM
      concentration of HCHO has been chosen for combination treatment of the three cell
      lines with a series of concentrations (0.2-100 microM) of resveratrol, a
      phytoestrogen occurring in various fruits. Resveratrol decreased the cytotoxicity
      of formaldehyde depending on cell line and point of time, especially in case of
      MCF-7 cells at 24 and 72 h, Vero cells at 24h and HepG2 cells at 48 h after
      treatment. Possible modes of interactions are discussed, considering the role of
      resveratrol in formaldehyde metabolism and also the estrogen receptor positivity
      of MCF-7 cells.

PMID- 17517525
TI  - IDC1, a pezizomycotina-specific gene that belongs to the PaMpk1 MAP kinase
      transduction cascade of the filamentous fungus Podospora anserina.
AB  - Components involved in the activation of the MAPK cascades in filamentous fungi
      are not well known. Here, we provide evidence that IDC1, a pezizomycotina
      specific gene is involved along with the PaNox1 NADPH oxidase in the nuclear
      localization of the PaMpk1 MAP kinase, a prerequisite for MAPK activity. Mutants
      of IDC1 display the same phenotypes as mutants in PaNox1 and PaMpk1, i.e., lack
      of pigment and of aerial hyphae, female sterility, impairment in hyphal
      interference and inability to develop Crippled Growth cell degeneration. As
      observed for the PaNox1 mutant, IDC1 mutants are hypostatic to PaMpk1 mutants.
      IDC1 seems to play a key role in sexual reproduction. Indeed, fertility is
      diminished in strains with lower level of IDC1. In strains over-expressing IDC1,
      protoperithecia reach a later stage of development towards perithecia without
      fertilization; however, upon fertilization maturation of fertile perithecia is
      diminished and delayed. In addition, heterokaryon construction shows that IDC1 is
      necessary together with PaNox1 in the perithecial envelope but not in the
      dikaryon resulting from fertilization.

PMID- 17517526
TI  - Nitrite infusion increases cerebral blood flow and decreases mean arterial blood
      pressure in rats: a role for red cell NO.
AB  - It has been proposed that the reduction of nitrite by red cells producing NO
      plays a role in the regulation of vascular tone. This hypothesis was investigated
      in rats by measuring the effect of nitrite infusion on mean arterial blood
      pressure (MAP), cerebral blood flow (CBF) and cerebrovascular resistance (CVR) in
      conjunction with the accumulation of red cell NO. The relative magnitude of the
      effects on MAP and CBF as well as the time dependent changes during nitrite
      infusion are used to distinguish between the effects on the peripheral
      circulation and the effects on the cerebral circulation undergoing cerebral
      autoregulation. The nitrite infusion was found to reverse the 96% increase in MAP
      and the 13% decrease in CBF produced by L-NAME inhibition of e-NOS. At the same
      time there was a 20-fold increase in oxygen stable red cell NO. Correlations of
      the red cell NO for individual rats support a role for red cell nitrite reduction
      in regulating vascular tone in both the peripheral and the cerebral circulation.
      Furthermore, data obtained prior to treatment is consistent with a contribution
      of red cell reduced nitrite in regulating vascular tone even under normal
      conditions.

PMID- 17517527
TI  - Expression of cyclooxygenase-2 in canine nasal carcinomas.
AB  - Cyclooxygenase(COX)-2 expression was evaluated in 24 paraffin-embedded canine
      nasal carcinoma tissue samples by immunohistochemistry. Several different tumor
      types were represented, including carcinomas, adenocarcinomas and squamous cell
      carcinomas. COX-2 expression was identified in 17/24 cases (71%). The proportion
      of positive cells expressing COX-2 ranged from 10 to 95% and COX-2 expression was
      predominantly localized in the cytoplasm. Treatment with a COX-2 inhibitor should
      be investigated, along with the utilization of COX-2 expression as a prognostic
      marker.

PMID- 17517528
TI  - Time-of-flight variant to image mixing of granular media in a 3D fluidized bed.
AB  - This paper describes a variant of time-of-flight magnetic resonance (MR) imaging
      that provides a method of measuring the inherent mixing in a fluidized bed
      without the introduction of tracer particles. The modifications to conventional
      time-of-flight imaging enable the measurement of the axial mixing of a precisely
      controlled initial particle distribution, thereby providing measurements suitable
      for a direct comparison with models of solids mixing in granular systems. The
      imaging sequence is applied to characterize mixing, over time scales of 25-1000
      ms, in a gas-fluidized bed of Myosotis seed particles; mixing over short
      timescales, inaccessible using conventional tracer techniques, is studied using
      this technique. The mixing pattern determined by this pulse sequence is used in
      conjunction with MR velocity images of the motion of the particles to provide new
      insight into the mechanism of solids mixing in granular systems.

PMID- 17517529
TI  - Biselective refocusing pulses and the SERF experiment.
AB  - The SERF experiment is a variant of the homonuclear J-resolved experiment, in
      which a single coupling constant is measured. It consists of a single chemical
      shift selective excitation that is followed by a biselective spin echo. Recent
      articles mention the existence of artefacts in SERF spectra that are supposedly
      related to pulse imperfections. This article presents a detailed study of the
      biselective refocusing pulses. It also reports a method for predicting the
      position and amplitude of the expected and unexpected 2D spectral peaks in SERF
      spectra. Artefacts can be partially eliminated by phase cycling or by the
      introduction of static field gradient pulses in the acquisition sequence. A
      procedure to obtain of pure absorption peaks in SERF spectra is proposed.

PMID- 17517530
TI  - TNF-alpha antagonists and the prevention of hospitalisation for chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: TNF-alpha may be important in the pathogenesis of COPD. Consequently,
      the use of TNF-alpha antagonists has been advocated for its treatment. METHODS:
      We conducted an observational study to evaluate the effectiveness of TNF-alpha
      antagonists in preventing COPD hospitalisations in a cohort of patients diagnosed
      with both RA and COPD identified from a health claims database. A nested case
      control approach was used to match each case hospitalised to 10 controls on age
      and cohort entry date. Data on prescribed medications during the year prior to
      the index date were obtained. Rate ratios (RR) of COPD hospitalisation were
      estimated by conditional logistic regression, after adjustment for COPD severity
      and concomitant RA medication use. RESULTS: The cohort included 15,771 subjects
      with both RA and COPD, of which 1205 were hospitalised for COPD during follow-up.
      The adjusted RR of COPD hospitalisation associated with the use of TNF-alpha
      antagonists was 0.62 (95% confidence interval (CI) 0.43-0.89). This rate
      reduction was due to etanercept (RR 0.49, 95% CI 0.29-0.82) but not infliximab
      (RR 0.95, 95% CI 0.59-1.52). CONCLUSION: Our finding of a halving in the rate of
      COPD hospitalisation associated with the use of etanercept corroborates the
      potential importance of TNF-alpha in the pathogenesis of COPD. This study
      supports the initiation of randomised controlled trials of this TNF-alpha
      antagonist among COPD patients at high risk of severe exacerbations.

PMID- 17517531
TI  - Molecular and biochemical characterization of the GALK1 gene in Korean patients
      with galactokinase deficiency.
AB  - Galactokinase (GALK) deficiency is an autosomal recessive disorder characterized
      by elevation of blood galactose concentration and diminished galactose-1
      phosphate, leading to the production of galactitol. To investigate the molecular
      defects of GALK1 gene and the biochemical characteristics of their mutant
      proteins, PCR-direct sequencing and in vitro expression analysis in Cos7 cells
      were performed in five Korean patients with GALK deficiency galactosemia. Four
      missense mutations (p.G137R, p.R256W, p.R277Q, and p.V281M) and one small
      insertion (c.850_851insG) were identified. Among four patients with severely
      reduced GALK activity, two were found to be homozygotes for p.R256W and the other
      two were compound heterozygotes for different molecular defects (p.G137R/p.R277Q
      and p.V281M/c.850_851insG). One Patient with moderately decreased GALK activity
      was heterozygous for p.R256W. Expression analysis in Cos7 cells confirmed that
      each of the mutations resulted in reduction of GALK activity and caused GALK
      deficiency.

PMID- 17517532
TI  - A method exploiting syntactic patterns and the UMLS semantics for aligning
      biomedical ontologies: the case of OBO disease ontologies.
AB  - The OBO ontologies include more than 50 standard vocabularies that cover
      different domains, including genomics, chemistry, anatomy and phenotype. Ontology
      alignment is a means to build consistent biomedical ontologies compatible with
      standard vocabularies and dedicated to specific domains, such as cancer. An
      alignment is defined as a set of pairs of concepts, coming from two ontologies,
      related by a relation R, R not being restricted to the equivalence or subsumption
      relations. Alignment is performed in three major steps: first, the concepts that
      are equivalent in the ontologies are identified; second the pairs of concepts
      that are related although not equivalent are searched for; third the relations
      between the concepts are characterized. We have developed a method to align
      ontologies that exploits the compositionality of the terms in OBO ontologies,
      uses the UMLS to provide synonyms and relations, and defines syntactico-semantic
      patterns that characterize semantically the relations between concepts. We have
      applied it to four OBO phenotype ontologies: mouse pathology, human disease,
      mammalian phenotype, and PATO. We found 386 pairs of equivalent concepts and
      20,461 pairs of concepts where one concept name is included in the other term.
      Among the 20,460 inclusions, we were able to provide a semantic categorization
      for 2682 relations. In 2552 cases, the relation was present and semantically
      defined in the UMLS Metathesaurus, in 131 cases the relation was characterized
      through semantic patterns. Our approach may help to find the semantic relations
      between concepts in ontologies.

PMID- 17517533
TI  - The demographic bias of Email as a survey method in a pediatric emergency
      population.
AB  - Email has been considered as a communication medium between patients and
      clinicians in pediatric emergency departments, but the demographic bias involved
      in using email has not been fully explored. We developed a paper based survey to
      explore access, willingness to participate and the demographic bias of email
      within our parent population. METHODS: To 1733 possible subjects, 1200 surveys
      were distributed with a return of 1018, a survey response rate of 85%, and a
      population response rate of 59%. RESULTS: Subjects from families with incomes
      less than $60,000 per year had lower access rates (OR=0.40, 95% CI [0.25, 0.62]),
      as did those with lower education (OR=0.37, [0.17, 0.81]). Employment outside of
      the home was associated with increased email access rates (OR=1.79, 95% CI [1.19,
      2.70]). Visible minority status was associated with an increased willingness to
      participate (OR=1.84, 95% CI [1.10, 3.06]) as was low education (OR=2.12, 95% CI
      [1.04, 4.32]). The population of theoretical responders to an email based quality
      assurance process would have been significantly different from the base
      population of adults accompanying children to our emergency department as a
      result of these biases. CONCLUSION: We have demonstrated a degree of demographic
      bias in email access rates, negatively affecting those individuals with lower
      income, less employment, and lower education. Email based surveys directed at
      parents in pediatric emergency departments should include questions on income,
      employment and education in order to permit those who analyze the data to correct
      for these variables. More research is needed to confirm these findings.

PMID- 17517534
TI  - Is bladder voiding in sleeping preterm infants accompanied by arousals?
AB  - BACKGROUND: As it has been reported that bladder voiding in sleeping full-term
      infants is consistently accompanied by a cortical arousal, it was the aim of the
      present study to find out whether this could also hold true for preterm infants.
      METHODS: Polygraphic recordings were performed in 21 healthy preterm infants (10
      female). The infants' gestational age at birth was 31+/-2.7 weeks and postnatal
      age at study entry was 26+/-8 days (mean+/-standard deviation). Bladder voiding
      was recorded by an adapted enuresis detector which was connected to the
      polygraphic computer unit. Arousals were defined as suggested by the
      International Paediatric Work Group on Arousals. RESULTS: Bladder voiding was
      recorded 50+/-7 min after sleep onset and occurred during quiet sleep (QS) only.
      Heart rate (HR), respiratory frequency (RF) and electroencephalographic (EEG)
      frequency did not change during bladder voiding. Body movements were recorded in
      52% of all preterm infants. CONCLUSION: We found that bladder voiding was not
      accompanied by arousals, suggesting that the arousal process in preterm infants
      may be delayed due to immaturity.

PMID- 17517535
TI  - Clinical characteristics and outcome of patients diagnosed with psychogenic
      nonepileptic seizures: a 5-year review.
AB  - OBJECTIVE: The goal of this article was to describe the clinical characteristics
      and outcomes of patients diagnosed with psychogenic nonepileptic seizures (PNES).
      METHODS: We conducted a retrospective review of patients diagnosed with PNES in a
      5-year period. RESULTS: Fifty patients with PNES were identified, giving an
      estimated incidence of 0.91/100,000 per annum. Thirty-eight were included for
      review, 15 of whom were male (39%). Eighteen patients had been diagnosed with
      epilepsy as well as PNES (47%). We demonstrated a gender difference in our
      patients, with males having higher seizure frequencies, more antiepileptic drug
      use, and a longer interval before diagnosis of PNES. Females were diagnosed with
      other conversion disorders more often than males. Impaired social function was
      observed in PNES, as was resistance to psychological interventions with a
      subsequent poor response to treatments. CONCLUSIONS: PNES remains a difficult
      condition to treat, and may affect males in proportions higher than those
      described in previous studies.

PMID- 17517536
TI  - Mirtazapine does not affect pentylenetetrazole- and maximal electroconvulsive
      shock-induced seizures in mice.
AB  - Mirtazapine is an antidepressant exhibiting both noradrenergic and serotonergic
      activity. We have investigated the effects of mirtazapine on pentylenetetrazole
      (PTZ)- and maximal electroconvulsive shock (MES)-induced seizures in mice.
      Mirtazapine (1.25-20mg/kg) or saline was administered, and locomotor activity was
      evaluated for 30 min. One hour after administration of mirtazapine (1.25-5mg/kg)
      or saline, PTZ (80 mg/kg) was injected intraperitoneally into the mice.
      Immediately afterward, times of onset of the first myoclonic jerk (FMJ),
      generalized clonic seizures (GCS), and tonic extension (TE) were recorded. In the
      MES groups, we used the MES protocol to induce convulsions characterized by tonic
      hindlimb extension. Similarly, 1h after mirtazapine or saline administration, an
      electroshock was evoked by ear-clip electrodes to induce convulsion. Mirtazapine,
      at 10 and 20 mg/kg, depressed locomotor activity. Doses of 1.25-5mg/kg had no
      significant effect on the time of onset of FMJ, GCS, or TE induced by PTZ; on the
      duration of GCS and TE; or on the latency to reinstatement of the righting reflex
      after MES administration. Our results suggest that mirtazapine neither aggravates
      nor alleviates PTZ- or MES-induced seizures in mice.

PMID- 17517537
TI  - The genes coding for the MYST family histone acetyltransferases, Tip60 and Mof,
      are expressed at high levels during sperm development.
AB  - Co-activators of transcription with histone acetyltransferase activity have
      essential functions in a wide range of cellular and developmental processes. We
      investigated the expression of the genes coding for two closely related MYST
      family histone acetyltransferases, Tip60 and Mof, in mouse development and adult
      organs. The Tip60 and the Mof genes are both very highly expressed in the testes
      compared to other organs. High-level Tip60 gene expression is restricted to late
      pachytene and diplotene stages of sperm development. Likewise, the Mof gene is
      expressed at high levels in late pachytene and diplotene spermatocytes, but in
      contrast to Tip60, Mof is also expressed at high levels in round spermatids.
      Expression of both Mof and Tip60 was comparatively low in spermatogonia in adult
      testes. However Mof, but not Tip60 mRNA, was readily detected in germ cells
      during embryonic development.

PMID- 17517538
TI  - Validated HPLC method for the determination of gabapentin in human plasma using
      pre-column derivatization with 1-fluoro-2,4-dinitrobenzene and its application to
      a pharmacokinetic study.
AB  - A rapid, sensitive and accurate high-performance liquid chromatographic method
      with UV detection was developed and validated for the quantification of
      gabapentin in human plasma. Gabapentin was quantified using pre-column
      derivatization with 1-fluoro-2,4-dinitrobenzene following protein precipitation
      of plasma with acetonitrile. Amlodipine was used as internal standard. The
      chromatographic separation was carried out on a Nova-Pak C(18) column using a
      mixture of 50 mM NaH(2)PO(4) (pH=2.5)-acetonitrile (30:70, v/v) as mobile phase
      with UV detection at 360 nm. The flow rate was set at 1.5 ml/min. The method was
      linear over the range of 0.05-5 microg/ml of gabapentin in plasma (r(2)>0.999).
      The within-day and between-day precision values were in the range of 2-5%. The
      limit of quantification of the method was 0.05 microg/ml. The method was
      successfully used to study the pharmacokinetics of gabapentin in healthy
      volunteers.

PMID- 17517539
TI  - Determination of heterocyclic amines by capillary electrophoresis with UV-DAD
      detection using on-line preconcentration.
AB  - This paper proposed a method with capillary zone electrophoresis (CZE) for
      analysis of eight heterocyclic amines in a commercial meat matrix. The influence
      of composition, pH and concentration of buffer, and applied voltage were
      investigated. A 5 mmol/L formic acid-ammonium formate solution at pH 2.20 was
      chosen as the running electrolyte. Also several solid-phase extraction actions
      were performed for the clean-up of the samples. With 3s hydrodynamic injection,
      detection limits ranging from 0.554 to 1.783 microg/g was obtained. To improve
      sensitivity, field-amplified sample injection (FASI) was used with the conditions
      of 3 s hydrodynamic injection of a water plug and 25 s electrokinetic injection
      of the sample. And methanol-water (1:1 in volume) was applied as the sample
      solvent. Under above conditions, detection limits ranged from 1.329 to 19.39
      ng/g, which were at least 50 times lower than those with hydrodynamic injection.

PMID- 17517540
TI  - Treatment choices of hypertensive patients in Turkey.
AB  - Hypertension is a serious and common health problem experienced by people from
      all parts of the world. The authors' aim was to assess hypertensive patients'
      baseline health behaviors, health status, knowledge about their disease,
      lifestyles, behaviorial modifications, sources of information about their
      disease, and management of hypertension. The authors administered to 72
      hypertensive patients a questionnaire that asked about lifestyles, management of
      hypertensive attacks, and use of alternative treatments. The patients' mean Body
      Mass Index was 27 +/- 4.0 kg/m(2), and although a change of diet had been advised
      to most patients, compliance was low (34.2%). Only 23.6% of the patients were
      first diagnosed in primary care facilities. The most common traditional self
      treatments for hypertensive attacks were eating yogurt with garlic (27.8%) and
      eating sour foods (25%). A considerable proportion of patients acquired their
      knowledge about hypertension from the media. By using media, patient education
      and behavioral modification can be helpful in the treatment and control of
      hypertension.

PMID- 17517541
TI  - Quetiapine in the successful combination treatment of an assaultive patient with
      treatment-resistant schizoaffective disorder.
AB  - The author relates the case study of a 38-year-old man with schizoaffective
      disorder (bipolar type) refractory to multiple medications. This patient had a
      long history of psychiatric illness and had been hospitalized at least 15 times
      because of aggression, hostility, and psychosis. Two separate trials of
      risperidone and olanzapine resulted in adverse effects, including possible
      neuroleptic malignant syndrome. Quetiapine, as part of combination therapy, led
      to substantial reductions in the patient's schizoaffective disorder symptoms and
      problematic behaviors. The patient tolerated quetiapine and did not experience
      any adverse effects. Quetiapine may be a suitable treatment option in patients
      with schizoaffective disorder.

PMID- 17517542
TI  - Assessing subjective sleepiness during a night of sleep deprivation: examining
      the internal state and behavioral dimensions of sleepiness.
AB  - Investigators in previous research have indicated that subjective measures of
      sleepiness may separate into state- and behavior-based dimensions; however,
      researchers have not examined this under sleep deprivation conditions. The
      authors' purpose in this study was to examine several measures of subjective
      sleepiness under sleep deprivation conditions following completion of various
      tasks. Fourteen students participated in a 28-hour sleep deprivation study and
      completed vigilance and cognitive tasks 4 times during the night. The authors
      administered subjective measures of sleepiness after each task. Factor analyses
      indicated that when individuals were not excessively sleepy, subjective
      sleepiness measures separated into 2 dimensions: state and behavioral sleepiness.
      However, when individuals were more fatigued, there was no distinction between
      the state and behavior dimensions of sleepiness. The current results suggest that
      using measures that assess state and behavioral sleepiness separately could be
      useful in clinical and research settings when extreme levels of sleepiness are
      not expected.

PMID- 17517543
TI  - Biopsychosocial predictors of depressive mood in people with Parkinson's disease.
AB  - The incidence of depressive mood among people with Parkinson's disease (PD) is
      well documented, yet less is known about the biopsychosocial correlates of this
      low mood state. In this study, 82 people with PD (M age = 68 years, SD = 9.4)
      completed questionnaires related to the duration of their illness, social
      support, coping, relationship satisfaction, and depression. The authors entered
      variables that correlated significantly with depressive mood into a multiple
      regression analysis, and the variables in the final model explained 64% of the
      variance in depressive mood. Gross motor impairment (beta = .45), blaming self
      (beta = .41), avoidance (beta = .33), symptom severity (beta = .21), and
      recreational intimacy (beta = -.14) were strong predictors of depressive mood.
      The authors discuss the findings in terms of interventions aimed at reducing the
      use of emotion-focused strategies, encouraging recreational intimacy among people
      with PD and their partners, and educational programs that provide information on
      PD symptoms, to promote positive mood and adjustment among people with PD.

PMID- 17517544
TI  - Outcomes of a technology-based social norms intervention to deter alcohol use in
      freshman residence halls.
AB  - OBJECTIVE: The authors tested a prototype intervention designed to deter alcohol
      use in residence halls. PARTICIPANTS: Approximately 384 freshmen participated in
      the study over a 2-year period. METHODS: The authors devised a feedback method
      that assessed residents' blood alcohol concentration (BAC) at night and allowed
      the readings to be retrieved the next day via the Web. Residents in an
      intervention hall received their BAC readings as well as normative feedback. In a
      comparison hall, residents could retrieve only the BAC readings. RESULTS: The
      authors found statistically significant hall differences, but they were small in
      size and not meaningful. CONCLUSIONS: Qualitative findings suggest the
      intervention had an overall positive impact, but the actions of a subgroup of
      rebellious drinkers might have obscured the effect. Social norms interventions
      could provoke some episodes of excessive drinking in students who find these
      messages objectionable. More research is needed to evaluate delayed BAC feedback.

PMID- 17517545
TI  - Relationship of interpersonal behaviors and health-related control appraisals to
      patient satisfaction and compliance in a university health center.
AB  - OBJECTIVE: The authors' aim was to evaluate patient-provider relationships in a
      college health center. PARTICIPANTS: Eighty student patients and their health
      care providers. METHODS: Patients completed a measure of perceived health
      competence before a consultation and measures of provider participatory behavior
      and interpersonal behavior before and after the consultation. They evaluated
      their satisfaction with care and compliance after the consultation and again 2
      weeks later. Providers completed measures of their participatory behavior and
      patients' interpersonal behavior after the consultation. RESULTS: Patients
      preferred to be well informed and to have their preferences taken into account,
      and generally felt competent at managing their own health affairs. They indicated
      they obtained the high level of participation they desired. Patients desired and
      actually experienced friendly and submissive providers. Degree of match between
      patients' desired and actual level of involvement in their care was associated
      with greater satisfaction. A greater match between the extent to which they
      desired the provider to be affiliative and the provider's actual affiliative
      behavior was associated with more satisfaction. No variables were predictive of
      patient compliance. CONCLUSION: The authors discuss results in terms of the
      influence of situational factors characteristic of a college health center.

PMID- 17517546
TI  - Results of National Alcohol Screening Day: college demographics, clinical
      characteristics, and comparison with online screening.
AB  - OBJECTIVE: The authors evaluated the efficacy of the 2002 college-based National
      Alcohol Screening Day (NASD) by determining: (1) the demographic and clinical
      characteristics of the participants that were screened and (2) the degree to
      which those scoring at hazardous drinking levels received clinical intervention
      or were referred for further assessment or treatment. PARTICIPANTS: Of 45,368
      participants, 23,334 were screened and 14,598 received some form of clinical
      intervention, defined as advice or referral. METHODS: The authors conducted
      nonparametric and univariate analyses to test for statistical differences in
      demographics, clinical-characteristics, and interventions-as a function of
      screening mode. RESULTS: Nearly 34% of those screened in person had an AUDIT
      score of 8 or higher, indicating harmful or hazardous drinking. Of these, only
      10% had ever undergone alcohol treatment. More than 58% of those screened online
      scored 8 or higher, and of this group, fewer than 6% had ever undergone alcohol
      treatment. CONCLUSIONS: These data suggest that the in-person event and the
      online interactive program associated with NASD are serving markedly different
      populations, particularly with regard to clinical indicators.

PMID- 17517547
TI  - Smoking-cessation counseling practices of college/university health-care
      providers--a theory-based approach.
AB  - OBJECTIVE: The author's purpose in this study was to examine the relation between
      smoking cessation counseling self-efficacy, knowledge of smoking cessation
      counseling, motivation to counsel smokers, and barriers to performing smoking
      cessation counseling, relative to the smoking cessation counseling stage of
      change. PARTICIPANTS AND METHODS: Members of The American College Health
      Association, who are health-care providers (N=296), completed a survey measuring
      the predictor variables of knowledge, motivation, self-efficacy and perceived
      barriers, and the members' readiness for conducting smoking-cessation counseling
      with students. RESULTS: The majority reported that they were knowledgeable about
      smoking-cessation counseling practices, they were motivated to conduct
      counseling, and they had the confidence (self-efficacy) to perform smoking
      cessation counseling effectively. Significant barriers to performing smoking
      cessation counseling included the lack of reimbursement for counseling, lack of
      training in smoking-cessation counseling, and lack of resources for follow-up.
      The author found a moderate negative correlation between self-efficacy for
      smoking-cessation counseling and barriers to performing smoking-cessation
      counseling. CONCLUSION: The results suggest that researchers should address the
      barriers that prevent health-care providers from performing smoking-cessation
      counseling. Interventions on increasing healthcare providers' counseling self
      efficacy may be instrumental in moving them further along the stage continuum and
      increase their readiness to perform smoking cessation counseling.

PMID- 17517548
TI  - Predicting 1-year change in body mass index among college students.
AB  - OBJECTIVE: Despite beliefs about weight gain in college, few researchers have
      evaluated this phenomenon. PARTICIPANTS: Participants were 18- to 31-year-old
      students at a midwestern university. The dependent variable was body mass index
      (BMI) change. METHODS: The authors extracted predictor variables from a Health
      Risk Appraisal. These included clinical, medical history, medical usage,
      medications, pain or chronic conditions, perceptual measures, and behavioral
      factors. The authors performed an ordinal regression technique separately by
      gender. RESULTS: No predictors were significant for men. Women in the BMI gain
      group were (1) more likely to consume alcohol, use maladaptive coping behaviors,
      eat foods low in fiber, and consume caffeine; and (2) less likely to be stress
      free, to eat cruciferous vegetables, and to refrain from eating high-cholesterol
      foods. CONCLUSIONS: The lack of research on predictors of and interventions for
      reducing BMI gain among college students warrants more research.

PMID- 17517549
TI  - Substance use among college athletes: a comparison based on sport/team
      affiliation.
AB  - OBJECTIVE: Prior research shows that college athletes have higher rates of
      substance use, especially alcohol, than do college students who are not involved
      in athletics. To augment the literature, the author sought to determine which
      sports/teams are at the greatest risk for substance use. PARTICIPANTS: The author
      used data from the 1999 Harvard School of Public Health College Alcohol Study, a
      national survey of college and university students in the United States. METHODS:
      A series of chi-square and logistic regression models examined variation in
      substance use among college athletes on the basis of sport/team affiliation.
      RESULTS: Findings indicated that male hockey and female soccer athletes were the
      most likely to report substance use and that male basketball and cross
      country/track athletes reported lower levels of substance use. CONCLUSION: There
      is variation in substance use on the basis of sport/team affiliation, and future
      researchers should examine why certain groups of athletes have higher rates of
      substance use.

PMID- 17517551
TI  - 'Ladies and gentlemen, our speaker needs no introduction...'.

PMID- 17517550
TI  - Introduction to the American College Health Association's "Standards of practice
      for health promotion in higher education".

PMID- 17517554
TI  - OTC product: Children's Pepto.

PMID- 17517555
TI  - Role of pharmacists in managing neurologic and psychiatric disorders.

PMID- 17517557
TI  - OTC product: PediaCare Long-Acting Cough Freezer Pops.

PMID- 17517558
TI  - How should we measure medication adherence in clinical trials and practice?

PMID- 17517559
TI  - OTC product: Fibersure.

PMID- 17517560
TI  - APhA2006 House of Delegates action: forming consensus on contemporary issues that
      reflect the profession's priorities.

PMID- 17517561
TI  - Report of the 2006 APhA House of Delegates.

PMID- 17517566
TI  - OTC product: Zicam Cold and Flu Medicated Spoons.

PMID- 17517568
TI  - Confidentiality challenges and good clinical practices in human subjects
      research: striking a balance.
AB  - The Health Insurance Portability and Accountability Act (HIPPA) has been fully
      implemented in clinical practice and research settings. Although subject
      confidentiality has always been a concern, clinical researchers must now take
      extra care to attend to the mandates of privacy while also minding good clinical
      practice guidelines. Unanticipated conflicts may arise as a result of these dual
      priorities. This article presents two examples of potential challenges to
      confidentiality with comment from the bioethical perspective.

PMID- 17517569
TI  - Ambulatory activity intensity profiles, fitness, and fatigue in chronic stroke.
AB  - PURPOSE: The purpose of this study was to describe household and community
      ambulatory activity profiles and their relationship to fatigue and cardiovascular
      fitness in a sample of men and women with chronic hemiparetic stroke. METHOD: We
      quantified community-based ambulatory activity profiles in terms of step counts
      and intensity, along with cardiovascular fitness and fatigue severity, in a
      convenience sample of 79 men and women with chronic hemiparetic stroke. RESULTS:
      As captured by daily step activity monitoring, participants demonstrated
      extremely low step counts (1389 +/- 797 steps/day), and almost no step activity
      at high intensity (78 +/- 168 steps/day at a rate of >or=30 steps/ minute). Mean
      high intensity activity constituted less than 3 minutes/day. The mean VO2 peak
      was 13.02 +/- 4.26 mL/kg/min, consistent with profound aerobic deconditioning.
      Total, low, and high intensity ambulatory activity were associated with VO2 peak.
      Mean fatigue severity was 3.28 +/- 1.36 on a scale of 7.00, with 42% of the
      sample reporting severe fatigue. There were no statistically significant
      correlations between fatigue severity and ambulatory activity or fitness
      measures. CONCLUSION: Our results show that step activity intensity is strongly
      associated with cardiovascular fitness, lending credence to the hypothesis that
      rehabilitation interventions that build aerobic conditioning can influence daily
      activity. The challenge is to appreciate the features of ambulatory behavior
      after stroke and to use this information to integrate both exercise interventions
      and behavioral components into the successful translation of structured
      activities into home and community routines.

PMID- 17517570
TI  - Two sides to the caregiving story.
AB  - PURPOSE: This descriptive study examined problems and successes that a sample of
      73 adult caregivers new to the role expressed in the first year of caring for
      stroke survivors. Data were collected from May 2002 to December 2005. METHOD:
      Bimonthly, trained telephone interviewers asked the participants open-ended
      questions to elicit their experience in caregiving. Guided by Friedemann's
      framework of systemic organization, we analyzed the data using Colaizzi's method
      of content analysis. RESULTS: There were 2,455 problems and 2,687 successes
      reported. Three themes emerged from the problems: being frustrated in day-to-day
      situations (system maintenance in Friedemann's terms), feeling inadequate and
      turning to others for help (coherence), and struggling and looking for "normal"
      in caring (system maintenance vs. change). Three themes were attributed to the
      successes: making it through and striving for independence (system maintenance),
      doing things together and seeing accomplishments in the other (coherence), and
      reaching a new sense of normal and finding balance in life (individuation and
      system maintenance). CONCLUSION: These findings provided an in-depth, theorybased
      description of the experience of being a new caregiver and can help explain how
      caring can be a difficult yet rewarding experience. Knowledge of the changes over
      time allows health care professionals to tailor their interventions,
      understanding, and support.

PMID- 17517571
TI  - Transition experiences of stroke survivors following discharge home.
AB  - BACKGROUND: Little is known about the transition experiences of stroke survivors
      after discharge home. PURPOSE: The purpose of this article is to describe three
      domains of psychosocial experiences of stroke survivors during the first month
      following discharge for acute stroke. METHOD: Data were collected from 125 stroke
      survivors interviewed at 1 month following discharge home. RESULTS: Findings
      indicate that changes in sense of self, connectedness with others, and community
      integration presented the major challenges.

PMID- 17517572
TI  - Care coordination/home-telehealth for veterans with stroke and their caregivers:
      addressing an unmet need.
AB  - BACKGROUND: Stroke is a life-disrupting, costly event for many stroke patients
      and their families. An estimated 4.8 million stroke survivors are living in the
      community with some level of disability, and the incidence of stroke is expected
      to rise with correspondingly higher costs, both in dollars and other forms of
      burden for families of patients with stroke. Approximately 80,000 veterans have
      experienced a stroke, leaving approximately 40% with moderate residual
      impairments and 15%-30% with severe residual disability. PURPOSE: The purpose of
      this study was to identify postdischarge needs of veterans with stroke and their
      caregivers and to identify how to design a care coordination/home-telehealth
      (CC/HT) program to address these needs. METHOD: Veterans and their caregivers (N
      = 22) were interviewed about their experiences with stroke, their postdischarge
      stroke recovery needs, and their experiences with the Veterans Administration's
      existing Care Coordination/Home-Telehealth (CC/HT) program. Data were analyzed
      using the process of grounded dimensional analysis. RESULTS: Core concepts
      identified were (a) assessing and managing the residual effects of stroke, and
      (b) shifting roles and responsibilities. CONCLUSION: The findings suggest that a
      comprehensive care coordination program that includes home telehealth could aid
      veterans and their caregivers in managing stroke recovery across the continuum of
      care at home and within the community. The results of the study can provide
      elements to be included in the CC/HT program.

PMID- 17517573
TI  - Post-stroke consultation service: a nurse-managed model for care delivery.
AB  - In 1989, a multidisciplinary consultation service devoted to providing primary
      care and rehabilitative care services to stroke survivors in the home was
      developed and tested at the University of Pennsylvania. This nurse-managed
      service, Post-Stroke Consultation Service, used the expertise of a nurse
      practitioner, geriatrician, physiatrist, physical therapists, home health care
      nurses, specialty care providers, families, and stroke survivors to develop and
      implement a plan of care that optimized health and function and would be
      sustainable over time. The service and its impact are described.

PMID- 17517574
TI  - Patient case study: in the case of Miss Christine.
AB  - Young stroke survivors often return to the community for ongoing recovery and
      reintegration. Their needs are somewhat different than their older counterparts,
      and they can be easily lost in the complex health care system of specialty and
      primary care services. This young woman and her outpatient rehabilitation
      providers exemplify some problems encountered and the persistent, caring, and
      successful work that teams can accomplish to maximize ongoing recovery.

PMID- 17517575
TI  - Virtual reality in stroke rehabilitation: a systematic review of its
      effectiveness for upper limb motor recovery.
AB  - PURPOSE: It is estimated that 50% to 75% of individuals who experience a stroke
      have persistent impairment of the affected upper limb (UL). There is a need to
      identify the best training strategies for retraining motor function of the UL.
      One intervention showing promise is virtual reality (VR), using either immersive
      or nonimmersive technology. Before recommending VR for use in clinical practice,
      it is important to understand the evidence regarding its effectiveness. METHOD:
      Two questions about the effectiveness of VR for UL rehabilitation in stroke were
      posed: (1) Is the use of immersive VR more effective than conventional therapy or
      no therapy in the rehabilitation of the UL in patients with hemiplegia? (2) Is
      the use of nonimmersive VR more effective than conventional therapy or no therapy
      in the rehabilitation of the UL in patients with hemiplegia? RESULTS: There is
      level 1b evidence suggesting an advantage to training in immersive VR
      environments versus no therapy in UL rehabilitation, and level 5 evidence for
      training in immersive VR versus conventional therapy. There is level 4 evidence
      showing conflicting results for training in nonimmersive VR versus no therapy,
      and level 2b evidence for training in nonimmersive VR versus conventional
      therapy. CONCLUSION: The current evidence on the effectiveness of using VR in the
      rehabilitation of the UL in patients with stroke is limited but sufficiently
      encouraging to justify additional clinical trials in this population.

PMID- 17517576
TI  - Osteoporosis treatment for patients with stroke.
AB  - PURPOSE: Little is known about the frequency of use of medications to maintain
      bone health for patients with stroke. This study was undertaken at an urban
      academic rehabilitation center to determine the prevalence of use of agents that
      could reduce bone loss in the stroke population. METHOD: A clinical database was
      searched for all patients 18 years old and over with stroke. The sample included
      1,219 inpatients and 2,776 outpatients. Demographic information (age, gender, and
      race) and medications were obtained for each patient. RESULTS: Among inpatients
      with stroke, 7.1% were taking osteoporosis medications (bisphosphonates,
      calcitonin, parathyroid hormone, or hormone replacement therapy), 11.3% were
      taking calcium supplements, 5.9% were taking vitamin D supplements, and 45.1%
      were taking multivitamin supplements. Among outpatients with stroke, 5.7% were
      taking osteoporosis medication, 5.8% were taking calcium supplements, 2.2% were
      taking vitamin D supplements, and 16.0% were taking multivitamin supplements.
      Patients being treated with specific osteoporosis therapies tended to be older
      and female by calculated odds ratios. The use of multivitamins was not related to
      age, gender, or race. CONCLUSION: Overall, relatively few stroke patients were
      taking osteoporosis medications or supplements. There is a need to increase the
      recognition, prevention, and treatment of bone loss in this high-risk population.

PMID- 17517577
TI  - Ethical issues with service animals.
AB  - The beneficial aspects of canines who provide services to people with
      disabilities have resulted in an explosion of a category of dogs that are bred
      and/or trained just for service purposes. Over the past 30 years, the role of
      most service dogs has become more prominent and more demanding. There are also
      concerns as to the well-being of these animals and questions regarding realistic
      expectations of them. The purpose of this article is to explore the utilization
      of service dogs in a rehabilitation health care setting. More specifically,
      ethical issues that are pertinent to the service dog's role will be identified
      and resolutions recommended.

PMID- 17517578
TI  - Memoirs.

PMID- 17517579
TI  - Updating the pharmacy technician certification examination: a practice analysis
      study.
AB  - OBJECTIVE: To update the Pharmacy Technician Certification Examination based on
      analysis of pharmacy practice elements (functions, responsibilities, and
      knowledge). DESIGN: Cross-sectional study. SETTING: United States in spring 2005.
      INTERVENTIONS: Web-based survey. PARTICIPANTS: Random sample of 4,000 Certified
      Pharmacy Technicians (CPhTs). MAIN OUTCOME MEASURES: Respondents' ratings of each
      of the practice analysis elements, the time spent performing each function, and
      the frequency of performance of each responsibility and use of each knowledge
      base. RESULTS: The survey return rate was 26%, and while the number of CPhTs
      practicing in community pharmacies was increased substantially over the 1999
      practice analysis survey, non-respondent analysis suggested under-representation
      of this group. The distribution of primary responsibilities of CPhTs (63%,
      assisting the pharmacist in serving patients; 23%, maintaining medication and
      inventory control systems; 14%, participating in pharmacy management and
      administration) was almost identical to the 1999 survey. In community,
      hospitals/health systems, and other pharmacy practice settings, pharmacy
      technicians were more typically involved in compounding medications and
      coordinating communications throughout the practice setting than in previous
      practice analyses. In community settings, pharmacy technicians were more
      frequently contacting prescribers for clarification of prescriptions and
      participating in quality assurance activities. CONCLUSION: Using results of this
      practice analysis, the Pharmacy Technician Certification Board revised the
      content outline for its Pharmacy Technician Certification Examination, and the
      new test specifications are being used for all tests administered during 2006.

PMID- 17517580
TI  - OTC product: Theraflu Thin Strips.

PMID- 17517583
TI  - Methylation and phosphorylation: a tangled relationship?

PMID- 17517584
TI  - Quantitative heteroduplex analysis.

PMID- 17517585
TI  - Oncopeptidomics: a useful approach for cancer diagnosis?

PMID- 17517586
TI  - The pain protective haplotype: introducing the modern genetic test.

PMID- 17517588
TI  - Alanine aminotransferase as an independent predictor of incident nonalcoholic
      fatty liver disease.

PMID- 17517589
TI  - Whole genome amplification and genetic analysis after extraction of proteins from
      dried blood spots.

PMID- 17517590
TI  - Pyrosequencing technology for automated detection of the BMP15 A180T variant in
      Spanish postmenopausal women.

PMID- 17517591
TI  - Determination of ITPase activity by capillary electrophoresis.

PMID- 17517592
TI  - Novel mutation (c.G1124A) in exon 9 of the APOB gene causes aberrant splicing and
      familial hypobetalipoproteinemia.

PMID- 17517593
TI  - Circulating cell-free placental mRNA in the maternal plasma as a predictive
      marker for twin-twin transfusion syndrome.

PMID- 17517594
TI  - Toenails: an easily accessible and long-term stable source of DNA for genetic
      analyses in large-scale epidemiological studies.

PMID- 17517595
TI  - Liposomal vaccines with conformation-specific amyloid peptide antigens define
      immune response and efficacy in APP transgenic mice.
AB  - We investigated the therapeutic effects of two different versions of Abeta(1-15
      (16)) liposome-based vaccines. Inoculation of APP-V717IxPS-1 (APPxPS-1) double
      transgenic mice with tetra-palmitoylated amyloid 1-15 peptide (palmAbeta(1-15)),
      or with amyloid 1-16 peptide (PEG-Abeta(1-16)) linked to a polyethyleneglycol
      spacer at each end, and embedded within a liposome membrane, elicited fast immune
      responses with identical binding epitopes. PalmAbeta(1-15) liposomal vaccine
      elicited an immune response that restored the memory defect of the mice, whereas
      that of PEG-Abeta(1-16) had no such effect. Immunoglobulins that were generated
      were predominantly of the IgG class with palmAbeta(1-15), whereas those elicited
      by PEG-Abeta(1-16) were primarily of the IgM class. The IgG subclasses of the
      antibodies generated by both vaccines were mostly IgG2b indicating
      noninflammatory Th2 isotype. CD and NMR revealed predominantly beta-sheet
      conformation of palmAbeta(1-15) and random coil of PEG-Abeta(1-16). We conclude
      that the association with liposomes induced a variation of the immunogenic
      structures and thereby different immunogenicities. This finding supports the
      hypothesis that Alzheimer's disease is a "conformational" disease, implying that
      antibodies against amyloid sequences in the beta-sheet conformation are preferred
      as potential therapeutic agents.

PMID- 17517596
TI  - Live-cell imaging reveals sequential oligomerization and local plasma membrane
      targeting of stromal interaction molecule 1 after Ca2+ store depletion.
AB  - Stromal interaction molecule 1 (STIM1) has recently been identified by our group
      and others as an endoplasmic reticulum (ER) Ca(2+) sensor that responds to ER
      Ca(2+) store depletion and activates Ca(2+) channels in the plasma membrane (PM).
      The molecular mechanism by which STIM1 transduces signals from the ER lumen to
      the PM is not yet understood. Here we developed a live-cell FRET approach and
      show that STIM1 forms oligomers within 5 s after Ca(2+) store depletion. These
      oligomers rapidly dissociated when ER Ca(2+) stores were refilled. We further
      show that STIM1 formed oligomers before its translocation within the ER network
      to ER-PM junctions. A mutant STIM1 lacking the C-terminal polybasic PM-targeting
      motif oligomerized after Ca(2+) store depletion but failed to form puncta at ER
      PM junctions. Using fluorescence recovery after photobleaching measurements to
      monitor STIM1 mobility, we show that STIM1 oligomers translocate on average only
      2 mum to reach ER-PM junctions, arguing that STIM1 ER-to-PM signaling is a local
      process that is suitable for generating cytosolic Ca(2+) gradients. Together, our
      live-cell measurements dissect the STIM1 ER-to-PM signaling relay into four
      sequential steps: (i) dissociation of Ca(2+), (ii) rapid oligomerization, (iii)
      spatially restricted translocation to nearby ER-PM junctions, and (iv) activation
      of PM Ca(2+) channels.

PMID- 17517597
TI  - Gram-positive three-component antimicrobial peptide-sensing system.
AB  - To survive during colonization or infection of the human body, microorganisms
      must circumvent mechanisms of innate host defense. Antimicrobial peptides
      represent a key component of innate host defense, especially in phagocytes and on
      epithelial surfaces. However, it is not known how the clinically important group
      of Gram-positive bacteria sense antimicrobial peptides to coordinate a directed
      defensive response. By determining the genome-wide gene regulatory response to
      human beta-defensin 3 in the nosocomial pathogen Staphylococcus epidermidis, we
      discovered an antimicrobial peptide sensor system that controls major specific
      resistance mechanisms of Gram-positive bacteria and is unrelated to the Gram
      negative PhoP/PhoQ system. It contains a classical two-component signal
      transducer and an unusual third protein, all of which are indispensable for
      signal transduction and antimicrobial peptide resistance. Furthermore, our data
      indicate that a very short, extracellular loop with a high density of negative
      charges in the sensor protein is responsible for antimicrobial peptide binding
      and the observed specificity for cationic antimicrobial peptides. Our study shows
      that Gram-positive bacteria have developed an efficient and unique way of
      controlling resistance mechanisms to antimicrobial peptides, which may provide a
      promising target for antimicrobial drug development.

PMID- 17517598
TI  - The origin of modern metabolic networks inferred from phylogenomic analysis of
      protein architecture.
AB  - Metabolism represents a complex collection of enzymatic reactions and transport
      processes that convert metabolites into molecules capable of supporting cellular
      life. Here we explore the origins and evolution of modern metabolism. Using
      phylogenomic information linked to the structure of metabolic enzymes, we sort
      out recruitment processes and discover that most enzymatic activities were
      associated with the nine most ancient and widely distributed protein fold
      architectures. An analysis of newly discovered functions showed enzymatic
      diversification occurred early, during the onset of the modern protein world.
      Most importantly, phylogenetic reconstruction exercises and other evidence
      suggest strongly that metabolism originated in enzymes with the P-loop hydrolase
      fold in nucleotide metabolism, probably in pathways linked to the purine
      metabolic subnetwork. Consequently, the first enzymatic takeover of an ancient
      biochemistry or prebiotic chemistry was related to the synthesis of nucleotides
      for the RNA world.

PMID- 17517599
TI  - Rapid enhancement of visual cortical response discriminability by
      microstimulation of the frontal eye field.
AB  - Visual attention provides a means of selecting among the barrage of information
      reaching the retina and of enhancing the perceptual discriminability of relevant
      stimuli. Neurophysiological studies in monkeys and functional imaging studies in
      humans have demonstrated neural correlates of these perceptual improvements in
      visual cortex during attention. Importantly, voluntary attention improves the
      discriminability of visual cortical responses to relevant stimuli. Recent work
      aimed at identifying sources of attentional modulation has implicated the frontal
      eye field (FEF) in driving spatial attention. Subthreshold microstimulation of
      the FEF enhances the responses of area V4 neurons to spatially corresponding
      stimuli. However, it is not known whether these enhancements include improved
      visual-response discriminability, a hallmark of voluntary attention. We used
      receiver-operator characteristic analysis to quantify how well V4 responses
      discriminated visual stimuli and examined how discriminability was affected by
      FEF microstimulation. Discriminability of responses to stable visual stimuli
      decayed over time but was transiently restored after microstimulation of the FEF.
      As observed during voluntary attention, the enhancement resulted only from
      changes in the magnitude of V4 responses and not in the relationship between
      response magnitude and variance. Enhanced response discriminability was apparent
      immediately after microstimulation and was reliable within 40 ms of
      microstimulation onset, indicating a direct influence of FEF stimulation on
      visual representations. These results contribute to the mounting evidence that
      saccade-related signals are a source of spatial attentive selection.

PMID- 17517600
TI  - Polycystic disease caused by deficiency in xylosyltransferase 2, an initiating
      enzyme of glycosaminoglycan biosynthesis.
AB  - The basic biochemical mechanisms underlying many heritable human polycystic
      diseases are unknown despite evidence that most cases are caused by mutations in
      members of several protein families, the most prominent being the polycystin gene
      family, whose products are found on the primary cilia, or due to mutations in
      posttranslational processing and transport. Inherited polycystic kidney disease,
      the most prevalent polycystic disease, currently affects approximately 500,000
      people in the United States. Decreases in proteoglycans (PGs) have been found in
      tissues and cultured cells from patients who suffer from autosomal dominant
      polycystic kidney disease, and this PG decrease has been hypothesized to be
      responsible for cystogenesis. This is possible because alterations in PG
      concentrations would be predicted to disrupt many homeostatic mechanisms of
      growth, development, and metabolism. To test this hypothesis, we have generated
      mice lacking xylosyltransferase 2 (XylT2), an enzyme involved in PG biosynthesis.
      Here we show that inactivation of XylT2 results in a substantial reduction in PGs
      and a phenotype characteristic of many aspects of polycystic liver and kidney
      disease, including biliary epithelial cysts, renal tubule dilation, organ
      fibrosis, and basement membrane abnormalities. Our findings demonstrate that
      alterations in PG concentrations can occur due to loss of XylT2, and that reduced
      PGs can induce cyst development.

PMID- 17517601
TI  - Evidence for emergence of diverse polioviruses from C-cluster coxsackie A viruses
      and implications for global poliovirus eradication.
AB  - The poliovirus (PV) eradication campaign is conducted on the premise that this
      virus, because of the lack of a zoonotic reservoir, will not reemerge once
      eradicated. This report examines the origin of PV using theoretical and
      experimental approaches. Our rooted phylogenetic analysis suggests a speciation
      of PV from a C-cluster coxsackie A virus (C-CAV) ancestor through mutation of the
      capsid that caused a receptor switch from intercellular adhesion molecule-1 to
      CD155, leading to a change of pathogenicity. This hypothesis is supported
      experimentally with chimeras generated from three different pairs of PV and C
      CAV. Those carrying the PV capsid and the replication proteins of C-CAVs
      replicated well, whereas their reciprocal counterparts were either debilitated or
      dead. This phenomenon of asymmetry is observed also in recombinants between PV1
      and C-CAV20, selected in tissue culture cells using a previously undescribed
      protocol. The recombinants are generated at frequencies of 10(-6) typical for PV
      interserotype recombination. Strikingly, they resemble genetically and
      phenotypically, including neurovirulence in CD155 transgenic mice, the large
      majority of circulating vaccine-derived PVs that have caused poliomyelitis
      outbreaks in different parts of the world. These data provide experimental
      evidence for C-CAVs being partners to PVs in generating diverse PV progeny by
      homologous recombination. They support speciation of a novel human pathogen (PV)
      from a pool of different human pathogens (C-CAVs). In a PV-free world without PV
      neutralizing antibodies, contemporary C-CAV, like their ancestor(s), could be
      fertile ground for a PV-like agent to emerge by mutation.

PMID- 17517602
TI  - Heat shock-inducible Cre/Lox approaches to induce diverse types of tumors and
      hyperplasia in transgenic zebrafish.
AB  - RAS family members are among the most frequently mutated oncogenes in human
      cancers. Given the utility of zebrafish in both chemical and genetic screens,
      developing RAS-induced cancer models will make large-scale screens possible to
      understand further the molecular mechanisms underlying malignancy. We developed a
      heat shock-inducible Cre/Lox-mediated transgenic approach in which activated
      human kRASG12D can be conditionally induced within transgenic animals by heat
      shock treatment. Specifically, double transgenic fish Tg(B-actin-LoxP-EGFP-LoxP
      kRASG12D; hsp70-Cre) developed four types of tumors and hyperplasia after heat
      shock of whole zebrafish embryos, including rhabdomyosarcoma, myeloproliferative
      disorder, intestinal hyperplasia, and malignant peripheral nerve sheath tumor.
      Using ex vivo heat shock and transplantation of whole kidney marrow cells from
      double transgenic animals, we were able to generate specifically kRASG12D-induced
      myeloproliferative disorder in recipient fish. This heat shock-inducible
      recombination approach allowed for the generation of multiple types of RAS
      induced tumors and hyperplasia without characterizing tissue-specific promoters.
      Moreover, these tumors and hyperplasia closely resemble human diseases at both
      the morphologic and molecular levels.

PMID- 17517603
TI  - Niche characteristics explain the reciprocal invasion success of stream salmonids
      in different continents.
AB  - An ability to understand and predict invasions is elemental for controlling the
      detrimental effects of introduced organisms on native biota. In eastern North
      America, European brown trout generally dominates over, and eventually replaces,
      the native brook trout. We show here that in northern Europe the pattern of
      replacement between these two species is reversed: when transferred to North
      European streams, brook trout spread extensively and partially replaced the
      native brown trout. The effect of brook trout on brown trout was habitat
      specific: brook trout excluded the native species only in small tributary streams
      where the reproduction of brown trout was severely reduced, whereas in larger
      streams brown trout was largely unaffected. Thus, the pattern of coexistence
      among the two salmonids in our study area is approaching that typically observed
      in North American streams. In both areas, brook trout ultimately settles in small
      headwater streams, but the process of replacement differs profoundly: in North
      Europe, brook trout replaces brown trout in headwater streams, whereas in North
      America these same streams are the ultimate refuge area for brook trout under the
      invasion pressure by brown trout. Our results underline the importance of knowing
      species' niche characteristics to explain and predict biological invasions.

PMID- 17517604
TI  - Structural insight into dimeric interaction of the SARAH domains from Mst1 and
      RASSF family proteins in the apoptosis pathway.
AB  - In eukaryotic cells, apoptosis and cell cycle arrest by the Ras --> RASSF --> MST
      pathway are controlled by the interaction of SARAH (for Salvador/Rassf/Hippo)
      domains in the C-terminal part of tumor suppressor proteins. The Mst1 SARAH
      domain interacts with its homologous domain of Rassf1 and Rassf5 (also known as
      Nore1) by forming a heterodimer that mediates the apoptosis process. Here, we
      describe the homodimeric structure of the human Mst1 SARAH domain and its
      heterotypic interaction with the Rassf5 and Salvador (Sav) SARAH domain. The Mst1
      SARAH structure forms a homodimer containing two helices per monomer. An
      antiparallel arrangement of the long alpha-helices (h2/h2') provides an elongated
      binding interface between the two monomers, and the short 3(10) helices (h1/h1')
      are folded toward that of the other monomer. Chemical shift perturbation
      experiments identified an elongated, tight-binding interface with the Rassf5
      SARAH domain and a 1:1 heterodimer formation. The linker region between the
      kinase and the SARAH domain is shown to be disordered in the free protein. These
      results imply a novel mode of interaction with RASSF family proteins and provide
      insight into the mechanism of apoptosis control by the SARAH domain.

PMID- 17517605
TI  - Threatening a rubber hand that you feel is yours elicits a cortical anxiety
      response.
AB  - The feeling of body ownership is a fundamental aspect of self-consciousness. The
      underlying neural mechanisms can be studied by using the illusion where a person
      is made to feel that a rubber hand is his or her own hand by brushing the
      person's hidden real hand and synchronously brushing the artificial hand that is
      in full view. Here we show that threat to the rubber hand can induce a similar
      level of activity in the brain areas associated with anxiety and interoceptive
      awareness (insula and anterior cingulate cortex) as when the person's real hand
      is threatened. We further show that the stronger the feeling of ownership of the
      artificial hand, the stronger the threat-evoked neuronal responses in the areas
      reflecting anxiety. Furthermore, across subjects, activity in multisensory areas
      reflecting ownership predicted the activity in the interoceptive system when the
      hand was under threat. Finally, we show that there is activity in medial wall
      motor areas, reflecting an urge to withdraw the artificial hand when it is under
      threat. These findings suggest that artificial limbs can evoke the same feelings
      as real limbs and provide objective neurophysiological evidence that the rubber
      hand is fully incorporated into the body. These findings are of fundamental
      importance because they suggest that the feeling of body ownership is associated
      with changes in the interoceptive systems.

PMID- 17517606
TI  - Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus
      by whole-genome sequencing.
AB  - The spread of multidrug-resistant Staphylococcus aureus (MRSA) strains in the
      clinical environment has begun to pose serious limits to treatment options. Yet
      virtually nothing is known about how resistance traits are acquired in vivo.
      Here, we apply the power of whole-genome sequencing to identify steps in the
      evolution of multidrug resistance in isogenic S. aureus isolates recovered
      periodically from the bloodstream of a patient undergoing chemotherapy with
      vancomycin and other antibiotics. After extensive therapy, the bacterium
      developed resistance, and treatment failed. Sequencing the first vancomycin
      susceptible isolate and the last vancomycin nonsusceptible isolate identified
      genome wide only 35 point mutations in 31 loci. These mutations appeared in a
      sequential order in isolates that were recovered at intermittent times during
      chemotherapy in parallel with increasing levels of resistance. The vancomycin
      nonsusceptible isolates also showed a 100-fold decrease in susceptibility to
      daptomycin, although this antibiotic was not used in the therapy. One of the
      mutated loci associated with decreasing vancomycin susceptibility (the vraR
      operon) was found to also carry mutations in six additional vancomycin
      nonsusceptible S. aureus isolates belonging to different genetic backgrounds and
      recovered from different geographic sites. As costs drop, whole-genome sequencing
      will become a useful tool in elucidating complex pathways of in vivo evolution in
      bacterial pathogens.

PMID- 17517607
TI  - Development of autoimmunity in mice lacking DNA topoisomerase 3beta.
AB  - Mice lacking DNA topoisomerase 3beta are predisposed to a shortened lifespan,
      infertility, and lesions in multiple organs resulting from inflammatory
      responses. Examination of the immune system of 6- and 52-week-old top3beta(-/-)
      mice revealed no significant aberrations in their central and peripheral
      tolerance or in T lymphocyte activation. However, the older but not the younger
      cohort shows a high incidence of serum autoantibodies relative to their
      TOP3beta(+/+) age-mates. The mutant mice also show an increase in numerical
      aberrations of chromosomes in splenocytes and bone marrow cells, as well as an
      increase in apoptotic cells in the thymus. Thus, it appears plausible that the
      inflammatory lesions in top3beta(-/-) mice are caused by the development of
      autoimmunity as they age: Chromosomal abnormalities in top3beta(-/-) mice might
      lead to a persistent increase in apoptotic cells, which might in turn lead to the
      progression of autoimmunity.

PMID- 17517608
TI  - The emergence of a superorganism through intergroup competition.
AB  - Surveys of insect societies have revealed four key, recurring organizational
      trends: (i) The most elaborated cooperation occurs in groups of relatives. (ii)
      Cooperation is typically more elaborate in species with large colony sizes than
      in species with small colony sizes, the latter exhibiting greater internal
      reproductive conflict and lesser morphological and behavioral specialization.
      (iii) Within a species, per capita brood output typically declines as colony size
      increases. (iv). The ecological factors of resource patchiness and intergroup
      competition are associated with the most elaborated cooperation. Predictions of
      all four patterns emerge elegantly from a game-theoretic model in which within
      group tug-of-wars are nested within a between-group tug-of-war. In this
      individual selection model, individuals are faced with the problem of how to
      partition their energy between investment in intercolony competition versus
      investment in intracolony competition, i.e., internal tugs-of-war over shares of
      the resources gained through intergroup competition. An individual's
      evolutionarily stable investment in between-group competition (i.e., within-group
      cooperation) versus within-group competition is shown to increase as within-group
      relatedness increases, to decrease as group size increases (for a fixed number of
      competing groups), to increase as the number of competing groups in a patch
      increases, and to decrease as between-group relatedness increases. Moreover, if
      increasing patch richness increases both the number of individuals within a group
      and the number of competing groups, greater overall cooperation within larger
      groups will be observed. The model presents a simple way of determining
      quantitatively how intergroup conflict will propel a society forward along a
      "superorganism continuum."

PMID- 17517609
TI  - Effect of plasmodial RESA protein on deformability of human red blood cells
      harboring Plasmodium falciparum.
AB  - During intraerythrocytic development, Plasmodium falciparum exports proteins that
      interact with the host cell plasma membrane and subplasma membrane-associated
      spectrin network. Parasite-exported proteins modify mechanical properties of host
      RBCs, resulting in altered cell circulation. In this work, optical tweezers
      experiments of cell mechanical properties at normal physiological and febrile
      temperatures are coupled, for the first time, with targeted gene disruption
      techniques to measure the effect of a single parasite-exported protein on host
      RBC deformability. We investigate Pf155/Ring-infected erythrocyte surface antigen
      (RESA), a parasite protein transported to the host spectrin network, on
      deformability of ring-stage parasite-harboring human RBCs. Using a set of
      parental, gene-disrupted, and revertant isogenic clones, we found that RESA plays
      a major role in reducing deformability of host cells at the early ring stage of
      parasite development, but not at more advanced stage. We also show that the
      effect of RESA on deformability is more pronounced at febrile temperature, which
      ring-stage parasite-harboring RBCs can be exposed to during a malaria attack,
      than at normal body temperature.

PMID- 17517610
TI  - Protection of the glutamate pool concentration in enteric bacteria.
AB  - The central nitrogen metabolic circuit in enteric bacteria consists of three
      enzymes: glutamine synthetase, glutamate synthase (GOGAT), and glutamate
      dehydrogenase (GDH). With the carbon skeleton provided by 2-oxoglutarate,
      ammonia/ammonium (NH(4)(+)) is assimilated into two central nitrogen
      intermediates, glutamate and glutamine. Although both serve as nitrogen donors
      for all biosynthetic needs, glutamate and glutamine play different roles.
      Internal glutamine serves as a sensor of external nitrogen availability, and its
      pool concentration decreases upon nitrogen limitation. A high glutamate pool
      concentration is required to maintain the internal K(+) pool. The configuration
      of high glutamate and low glutamine pools was disrupted in GOGAT(-) mutants under
      low NH(4)(+) conditions: the glutamate pool was low, the difference between
      glutamate and glutamine was diminished, and growth was defective. When a GOGAT(-)
      mutant was cultured in an NH(4)(+)-limited chemostat, two sequential spontaneous
      mutations occurred. Each resulted in a suppressor mutant that outgrew its
      predecessor in the chemostat. The first suppressor overexpressed GDH, and the
      second also had a partially impaired glutamine synthetase. The result was a
      triple mutant in which NH(4)(+) was assimilated by two enzymes instead of the
      normal three and yet glutamate and glutamine pools and growth were essentially
      normal. The results indicate preference for the usual ratio of glutamate and
      glutamine and the resilient and compensatory nature of the circuit on pool
      control. Analysis of other suppressor mutants selected on solid medium suggests
      that increased GDH expression is the key for rescue of the growth defect of
      GOGAT(-) mutants under low NH(4)(+) conditions.

PMID- 17517611
TI  - Pph3-Psy2 is a phosphatase complex required for Rad53 dephosphorylation and
      replication fork restart during recovery from DNA damage.
AB  - Activation of the checkpoint kinase Rad53 is a critical response to DNA damage
      that results in stabilization of stalled replication forks, inhibition of late
      origin initiation, up-regulation of dNTP levels, and delayed entry to mitosis.
      Activation of Rad53 is well understood and involves phosphorylation by the
      protein kinases Mec1 and Tel1 as well as in trans autophosphorylation by Rad53
      itself. However, deactivation of Rad53, which must occur to allow the cell to
      recover from checkpoint arrest, is not well understood. Here, we present genetic
      and biochemical evidence that the type 2A-like protein phosphatase Pph3 forms a
      complex with Psy2 (Pph3-Psy2) that binds and dephosphorylates activated Rad53
      during treatment with, and recovery from, methylmethane sulfonate-mediated DNA
      damage. In the absence of Pph3-Psy2, Rad53 dephosphorylation and the resumption
      of DNA synthesis are delayed during recovery from DNA damage. This delay in DNA
      synthesis reflects a failure to restart stalled replication forks, whereas,
      remarkably, genome replication is eventually completed by initiating late origins
      of replication despite the presence of hyperphosphorylated Rad53. These findings
      suggest that Rad53 regulates replication fork restart and initiation of late
      firing origins independently and that regulation of these processes is mediated
      by specific Rad53 phosphatases.

PMID- 17517612
TI  - The beginning of the end: links between ancient retroelements and modern
      telomerases.

PMID- 17517613
TI  - Completing a pathway to plant vitamin C synthesis.

PMID- 17517614
TI  - Nanoprobes with near-infrared persistent luminescence for in vivo imaging.
AB  - Fluorescence is increasingly used for in vivo imaging and has provided remarkable
      results. Yet this technique presents several limitations, especially due to
      tissue autofluorescence under external illumination and weak tissue penetration
      of low wavelength excitation light. We have developed an alternative optical
      imaging technique by using persistent luminescent nanoparticles suitable for
      small animal imaging. These nanoparticles can be excited before injection, and
      their in vivo distribution can be followed in real-time for more than 1 h without
      the need for any external illumination source. Chemical modification of the
      nanoparticles' surface led to lung or liver targeting or to long-lasting blood
      circulation. Tumor mass could also be identified on a mouse model.

PMID- 17517615
TI  - A new paradigm for electrostatic catalysis of radical reactions in vitamin B12
      enzymes.
AB  - The catalytic power of enzymes containing coenzyme B(12) cofactor has been, in
      some respects, the "last bastion" for the strain hypothesis. The present work
      explores the origin of this effect by using simulation methods that overcome the
      sampling difficulties of previous energy minimization studies. It is found that
      the major part of the catalytic effect is due to the electrostatic interaction
      between the ribose and the protein, and that the strain contribution is very
      small. Remarkably, enzymes can use electrostatic effects even in a radical
      process, when the charge distribution of the reacting fragments does not change
      significantly during the reaction. Electrostatic catalysis can, in such cases, be
      obtained by attaching a polar group to the leaving fragment and designing an
      active site that interacts more strongly with this group in the product state
      than in the reactant state. The finding that evolution had to use this trick
      provides further evidence to the observation that it is extremely hard to
      catalyze enzymatic reactions by nonelectrostatic factors. The trick used by B(12)
      enzymes may, in fact, be a very powerful new strategy in enzyme design.

PMID- 17517616
TI  - Single-molecule force spectroscopy reveals a mechanically stable protein fold and
      the rational tuning of its mechanical stability.
AB  - It is recognized that shear topology of two directly connected force-bearing
      terminal beta-strands is a common feature among the vast majority of mechanically
      stable proteins known so far. However, these proteins belong to only two distinct
      protein folds, Ig-like beta sandwich fold and beta-grasp fold, significantly
      hindering delineating molecular determinants of mechanical stability and rational
      tuning of mechanical properties. Here we combine single-molecule atomic force
      microscopy and steered molecular dynamics simulation to reveal that the de novo
      designed Top7 fold [Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker
      D (2003) Science 302:1364-1368] represents a mechanically stable protein fold
      that is distinct from Ig-like beta sandwich and beta-grasp folds. Although the
      two force-bearing beta strands of Top7 are not directly connected, Top7 displays
      significant mechanical stability, demonstrating that the direct connectivity of
      force-bearing beta strands in shear topology is not mandatory for mechanical
      stability. This finding broadens our understanding of the design of mechanically
      stable proteins and expands the protein fold space where mechanically stable
      proteins can be screened. Moreover, our results revealed a substructure-sliding
      mechanism for the mechanical unfolding of Top7 and the existence of two possible
      unfolding pathways with different height of energy barrier. Such insights enabled
      us to rationally tune the mechanical stability of Top7 by redesigning its
      mechanical unfolding pathway. Our study demonstrates that computational biology
      methods (including de novo design) offer great potential for designing proteins
      of defined topology to achieve significant and tunable mechanical properties in a
      rational and systematic fashion.

PMID- 17517617
TI  - A connecting hinge represses the activity of endothelial nitric oxide synthase.
AB  - In mammals, endothelial nitric oxide synthase (eNOS) has the weakest activity,
      being one-tenth and one-sixth as active as the inducible NOS (iNOS) and the
      neuronal NOS (nNOS), respectively. The basis for this weak activity is unclear.
      We hypothesized that a hinge element that connects the FMN module in the
      reductase domain but is shorter and of unique composition in eNOS may be
      involved. To test this hypothesis, we generated an eNOS chimera that contained
      the nNOS hinge and two mutants that either eliminated (P728IeNOS) or incorporated
      (I958PnNOS) a proline residue unique to the eNOS hinge. Incorporating the nNOS
      hinge into eNOS increased NO synthesis activity 4-fold, to an activity two-thirds
      that of nNOS. It also decreased uncoupled NADPH oxidation, increased the apparent
      K(m)O(2) for NO synthesis, and caused a faster heme reduction. Eliminating the
      hinge proline had similar, but lesser, effects. Our findings reveal that the
      hinge is an important regulator and show that differences in its composition
      restrict the activity of eNOS relative to other NOS enzymes.

PMID- 17517618
TI  - Primary protein response after ligand photodissociation in carbonmonoxy
      myoglobin.
AB  - Time-resolved UV resonance Raman (UVRR) spectroscopic studies of WT and mutant
      myoglobin were performed to reveal the dynamics of protein motion after ligand
      dissociation. After dissociation of carbon monoxide (CO) from the heme, UVRR
      bands of Tyr showed a decrease in intensity with a time constant of 2 ps. The
      intensity decrease was followed by intensity recovery with a time constant of 8
      ps. On the other hand, UVRR bands of Trp residues located in the A helix showed
      an intensity decrease that was completed within the instrument response time. The
      intensity decrease was followed by an intensity recovery with a time constant of
      approximately 50 ps and lasted up to 1 ns. The time-resolved UVRR study of the
      myoglobin mutants demonstrated that the hydrophobicity of environments around Trp
      14 decreased, whereas that around Trp-7 barely changed in the primary protein
      response. The present data indicate that displacement of the E helix toward the
      heme occurs within the instrument response time and that movement of the FG
      corner takes place with a time constant of 2 ps. The finding that the
      instantaneous motion of the E helix strongly suggests a mechanism in which
      protein structural changes are propagated from the heme to the A helix through
      the E helix motion.

PMID- 17517619
TI  - Functional neuroimaging and behavioral correlates of capacity decline in visual
      short-term memory after sleep deprivation.
AB  - Sleep deprivation (SD) impairs short-term memory, but it is unclear whether this
      is because of reduced storage capacity or processes contributing to appropriate
      information encoding. We evaluated 30 individuals twice, once after a night of
      normal sleep and again after 24 h of SD. In each session, we evaluated visual
      memory capacity by presenting arrays of one to eight colored squares.
      Additionally, we measured cortical responses to varying visual array sizes
      without engaging memory. The magnitude of intraparietal sulcus activation and
      memory capacity after normal sleep were highly correlated. SD elicited a pattern
      of activation in both tasks, indicating that deficits in visual processing and
      visual attention accompany and could account for loss of short-term memory
      capacity. Additionally, a comparison between better and poorer performers showed
      that preservation of precuneus and temporoparietal junction deactivation with
      increasing memory load corresponds to less performance decline when one is sleep
      deprived.

PMID- 17517620
TI  - Inhibition of type I and type III interferons by a secreted glycoprotein from
      Yaba-like disease virus.
AB  - Type I (IFN-alpha/beta) and type III (IFN-lambdas) IFNs are important components
      of the host antiviral response. Although type III IFNs possess intrinsic
      antiviral activity similar to that of type I IFNs, they signal through a specific
      unique receptor complex, and their functional importance for antiviral resistance
      is largely uncharacterized. Here, we report the first virus defense mechanism
      that directly targets type III IFNs. Y136 from Yaba-like disease virus, a
      yatapoxvirus, is a secreted glycoprotein related to protein B18 from Vaccinia
      virus, a known type I IFN-binding protein and a member of the Ig superfamily.
      Surprisingly, whereas B18 inhibits only type I IFNs, Y136 inhibits both type I
      and type III IFNs. Y136 inhibits IFN-induced signaling and suppresses IFN
      mediated biological activities including up-regulation of MHC class I antigen
      expression and induction of the antiviral state. These data demonstrate that
      poxviruses have developed unique strategies to counteract IFN-mediated antiviral
      protection and highlight the importance of type III IFNs in antiviral defense.
      These results suggest that type III IFNs may be an effective treatment for some
      poxviral infections.

PMID- 17517621
TI  - Common genetic variation within the low-density lipoprotein receptor-related
      protein 6 and late-onset Alzheimer's disease.
AB  - Genome-wide linkage studies have defined a broad susceptibility region for late
      onset Alzheimer's disease on chromosome 12, which contains the Low-Density
      Lipoprotein Receptor-Related Protein 6 (LRP6) gene, a coreceptor for Wnt
      signaling. Here, we report the association between common LRP6 variants and late
      onset Alzheimer's disease in a multicenter case-control series as well as in a
      large family-based series ascertained by the National Institute of Mental Health
      National Institute on Aging Genetics Initiative. As shown in the genome-wide
      linkage studies, our association depends mainly on apolipoprotein E-epsilon4
      (APOE-epsilon4) carrier status. Haplotype tagging single-nucleotide polymorphisms
      (SNPs) with a set of seven allelic variants of LRP6 identified a putative risk
      haplotype, which includes a highly conserved coding sequence SNP: Ile-1062 -->
      Val. Functional analyses revealed that the associated allele Val-1062, an allele
      previously linked to low bone mass, has decreased beta-catenin signaling in
      HEK293T cells. Our study unveils a genetic relationship between LRP6 and APOE and
      supports the hypothesis that altered Wnt/beta-catenin signaling may be involved
      in this neurodegenerative disease.

PMID- 17517622
TI  - Functional characterization of human PFTK1 as a cyclin-dependent kinase.
AB  - Cyclin-dependent kinases (CDKs) are crucial regulators of the eukaryotic cell
      cycle whose activities are controlled by associated cyclins. PFTK1 shares limited
      homology to CDKs, but its ability to associate with any cyclins and its
      biological functions remain largely unknown. Here, we report the functional
      characterization of human PFTK1 as a CDK. PFTK1 specifically interacted with
      cyclin D3 (CCND3) and formed a ternary complex with the cell cycle inhibitor
      p21(Cip1) in mammalian cells. We demonstrated that the kinase activity of PFTK1
      depended on CCND3 and was negatively regulated by p21(Cip1). Moreover, we
      identified the tumor suppressor Rb as a potential downstream substrate for the
      PFTK1/CCND3 complex. Importantly, knocking down PFTK1 expression by using siRNA
      caused cell cycle arrest at G(1), whereas ectopic expression of PFTK1 promoted
      cell proliferation. Taken together, our data strongly suggest that PFTK1 acts as
      a CDK that regulates cell cycle progression and cell proliferation.

PMID- 17517623
TI  - Roles of heat-shock protein 90 in maintaining and facilitating the
      neurodegenerative phenotype in tauopathies.
AB  - Neurodegeneration, a result of multiple dysregulatory events, is a lengthy
      multistep process manifested by accrual of mutant variants and abnormal
      expression, posttranslational modification, and processing of certain proteins.
      Accumulation of these dysregulated processes requires a mechanism that maintains
      their functional stability and allows the evolution of the neurodegenerative
      phenotype. In malignant cells, the capacity to buffer transformation has been
      attributed to heat-shock protein 90 (Hsp90). Although normal proteins seem to
      require limited assistance from the chaperone, their aberrant counterparts seem
      to be highly dependent on Hsp90. Whereas enhanced Hsp90 affinity for mutated or
      functionally deregulated client proteins has been observed for several
      oncoproteins, it is unknown whether Hsp90 plays a similar role for neuronal
      proteins and thus maintains and facilitates the transformed phenotype in
      neurodegenerative diseases. Tauopathies are neurodegenerative diseases
      characterized by aberrant phosphorylation and/or expression of Tau protein,
      leading to a time-dependent accumulation of Tau aggregates and subsequent
      neuronal death. Here, we show that the stability of p35, a neuronal protein that
      activates cyclin-dependent protein kinase 5 through complex formation leading to
      aberrant Tau phosphorylation, and that of mutant but not WT Tau protein is
      maintained in tauopathies by Hsp90. Inhibition of Hsp90 in cellular and mouse
      models of tauopathies leads to a reduction of the pathogenic activity of these
      proteins and results in elimination of aggregated Tau. The results identify
      important roles played by Hsp90 in maintaining and facilitating the degenerative
      phenotype in these diseases and provide a common principle governing cancer and
      neurodegenerative diseases.

PMID- 17517624
TI  - In situ measurement of the electrical potential across the phagosomal membrane
      using FRET and its contribution to the proton-motive force.
AB  - Phagosomes employ lytic enzymes, cationic peptides, and reactive oxygen
      intermediates to eliminate invading microorganisms. The effectiveness of these
      microbicidal mechanisms is potentiated by the acidic pH created by H(+)-pumping
      vacuolar-type ATPases (V-ATPases) on the phagosomal membrane. The degree of
      phagosomal acidification varies greatly among neutrophils, macrophages, and
      dendritic cells and can be affected by diseases like cystic fibrosis. The
      determinants of phagosomal pH are not completely understood, but the permeability
      to ions that neutralize the electrogenic effect of the V-ATPase has been proposed
      to play a central role. When counterion conductance is limiting, generation of a
      large membrane potential will dominate the proton-motive force (pmf), with a
      proportionally diminished pH gradient. Validation of this notion requires direct
      measurement of the electrical potential that develops across the phagosomal
      membrane (Psi(Phi)). We describe a noninvasive procedure to estimate Psi(Phi) in
      intact cells, based on fluorescence resonance energy transfer. This approach, in
      combination with measurements of phagosomal pH, enabled us to calculate the pmf
      across phagosomes of murine macrophages and to analyze the factors that limit
      acidification. At steady state, Psi(Phi) averaged 27 mV (lumen positive) and was
      only partially dissipated by inhibition of the V-ATPase with concanamycin A. The
      comparatively small contribution of the potential to the pmf suggests that proton
      pumping is not limited by the counterion permeability, a notion that was
      validated independently by using ionophores. Instead, phagosomal pH stabilizes
      when the rate of proton pumping, which decreases gradually as the lumen
      acidifies, is matched by the passive leak of proton equivalents.

PMID- 17517625
TI  - Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and
      in vivo and strategies for prevention.
AB  - Infection with dengue virus (DENV) or any other flavivirus induces cross
      reactive, but weakly neutralizing or nonneutralizing, antibodies that recognize
      epitopes involving the fusion peptide in the envelope glycoprotein. Humanized mAb
      IgG 1A5, derived from a chimpanzee, shares properties of cross-reactive
      antibodies. mAb IgG 1A5 up-regulated DENV infection by a mechanism of antibody
      dependent enhancement (ADE) in a variety of Fc receptor-bearing cells in vitro. A
      10- to 1,000-fold increase of viral yield in K562 cells, dependent on the DENV
      serotype, was observed over a range of subneutralizing concentrations of IgG 1A5.
      A significant increase of DENV-4 viremia titers (up to 100-fold) was also
      demonstrated in juvenile rhesus monkeys immunized with passively transferred
      dilutions of IgG 1A5. These results, together with earlier findings of ADE of
      DENV-2 infection by a polyclonal serum, establish the primate model for analysis
      of ADE. Considering the abundance of these cross-reactive antibodies, our
      observations confirm that significant viral amplification could occur during DENV
      infections in humans with prior infection or with maternally transferred
      immunity, possibly leading to severe dengue. Strategies to eliminate ADE were
      explored by altering the antibody Fc structures responsible for binding to Fc
      receptors. IgG 1A5 variants, containing amino acid substitutions from the Fc
      region of IgG2 or IgG4 antibodies, reduced but did not eliminate DENV-4-enhancing
      activity in K562 cells. Importantly, a 9-aa deletion at the N terminus of the
      CH(2) domain in the Fc region abrogated the enhancing activity.

PMID- 17517626
TI  - Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated
      antibody/Th1 responses and CD8 T cells through cross-priming.
AB  - The use of recombinant tumor antigen proteins is a realistic approach for the
      development of generic cancer vaccines, but the potential of this type of
      vaccines to induce specific CD8(+) T cell responses, through in vivo cross
      priming, has remained unclear. In this article, we report that repeated
      vaccination of cancer patients with recombinant NY-ESO-1 protein, Montanide ISA
      51, and CpG ODN 7909, a potent stimulator of B cells and T helper type 1 (Th1)
      type immunity, resulted in the early induction of specific integrated CD4(+) Th
      cells and antibody responses in most vaccinated patients, followed by the
      development of later CD8(+) T cell responses in a fraction of them. The
      correlation between antibody and T cell responses, together with the ability of
      vaccine-induced antibodies to promote in vitro cross-presentation of NY-ESO-1 by
      dendritic cells to vaccine-induced CD8(+) T cells, indicated that elicitation of
      NY-ESO-1-specific CD8(+) T cell responses by cross-priming in vivo was associated
      with the induction of adequate levels of specific antibodies. Together, our data
      provide clear evidence of in vivo cross-priming of specific cytotoxic T
      lymphocytes by a recombinant tumor antigen vaccine, underline the importance of
      specific antibody induction for the cross-priming to occur, and support the use
      of this type of formulation for the further development of efficient cancer
      vaccines.

PMID- 17517627
TI  - Double-stranded DNA and double-stranded RNA induce a common antiviral signaling
      pathway in human cells.
AB  - Virus infection triggers IFN immune defenses in infected cells in part through
      viral nucleic acid interactions, but the pathways by which dsDNA and DNA viruses
      trigger innate defenses are only partially understood. Here we present evidence
      that both retinoic acid-induced gene I (RIG-I) and mitochondrial antiviral
      signaling protein (MAVS) are required for dsDNA-induced IFN-beta promoter
      activation in a human hepatoma cell line (Huh-7), and that activation is
      efficiently blocked by the hepatitis C virus NS3/4A protease, which is known to
      block dsRNA signaling by cleaving MAVS. These findings suggest that dsDNA and
      dsRNA share a common pathway to trigger the innate antiviral defense response in
      human cells, although dsDNA appears to trigger that pathway upstream of the dsRNA
      interacting protein RIG-I.

PMID- 17517628
TI  - A remarkable female cranium of the early Oligocene anthropoid Aegyptopithecus
      zeuxis (Catarrhini, Propliopithecidae).
AB  - The most complete and best-preserved cranium of a Paleogene anthropoid ever
      found, that of a small female of the early Oligocene ( approximately 29-30 Ma)
      stem catarrhine species Aegyptopithecus zeuxis, was recovered from the Jebel
      Qatrani Formation (Fayum Depression, Egypt) in 2004. The specimen is that of a
      subadult and, in craniodental dimensions, is the smallest Aegyptopithecus
      individual known. High-resolution computed tomographic (microCT) scanning of the
      specimen's well preserved cranial vault confirms that Aegyptopithecus had
      relatively unexpanded frontal lobes and a brain-to-body mass ratio lower than
      those of living anthropoids. MicroCT scans of a male cranium recovered in 1966
      [Egyptian Geological Museum, Cairo (CGM) 40237] reveal that previous estimates of
      its endocranial volume were too large. Thus, some amount of encephalization
      evolved independently in platyrrhine and catarrhine anthropoids, and the relative
      brain size of the last common ancestor of crown Anthropoidea was probably
      strepsirrhine-like or smaller. A. zeuxis shows extreme sexual dimorphism in
      craniodental morphology (apparently to a degree otherwise seen only in some
      highly dimorphic Miocene catarrhines), and the crania of female Aegyptopithecus
      lack a number of morphological features seen in larger males that have been
      accorded phylogenetic significance in catarrhine systematics (e.g., a well
      developed rostrum, elongate sagittal crest, and frontal trigon). Although a
      unique pattern of craniofacial sexual dimorphism may have characterized advanced
      stem and basal crown catarrhines, expression of various allegedly "discrete"
      craniofacial features may have been intraspecifically variable in early
      catarrhine species due to high levels of dimorphism and so should be treated with
      caution in phylogenetic analyses.

PMID- 17517629
TI  - Disruptive mitochondrial DNA mutations in complex I subunits are markers of
      oncocytic phenotype in thyroid tumors.
AB  - Oncocytic tumors are a distinctive class of proliferative lesions composed of
      cells with a striking degree of mitochondrial hyperplasia that are particularly
      frequent in the thyroid gland. To understand whether specific mitochondrial DNA
      (mtDNA) mutations are associated with the accumulation of mitochondria, we
      sequenced the entire mtDNA in 50 oncocytic lesions (45 thyroid tumors of
      epithelial cell derivation and 5 mitochondrion-rich breast tumors) and 52 control
      cases (21 nononcocytic thyroid tumors, 15 breast carcinomas, and 16 gliomas) by
      using recently developed technology that allows specific and reliable
      amplification of the whole mtDNA with quick mutation scanning. Thirteen oncocytic
      lesions (26%) presented disruptive mutations (nonsense or frameshift), whereas
      only two samples (3.8%) presented such mutations in the nononcocytic control
      group. In one case with multiple thyroid nodules analyzed separately, a
      disruptive mutation was found in the only nodule with oncocytic features. In one
      of the five mitochondrion-rich breast tumors, a disruptive mutation was
      identified. All disruptive mutations were found in complex I subunit genes, and
      the association between these mutations and the oncocytic phenotype was
      statistically significant (P=0.001). To study the pathogenicity of these
      mitochondrial mutations, primary cultures from oncocytic tumors and corresponding
      normal tissues were established. Electron microscopy and biochemical and
      molecular analyses showed that primary cultures derived from tumors bearing
      disruptive mutations failed to maintain the mutations and the oncocytic
      phenotype. We conclude that disruptive mutations in complex I subunits are
      markers of thyroid oncocytic tumors.

PMID- 17517630
TI  - Oncogenic inhibition by a deleted in liver cancer gene requires cooperation
      between tensin binding and Rho-specific GTPase-activating protein activities.
AB  - The three deleted in liver cancer genes (DLC1-3) encode Rho-GTPase-activating
      proteins (RhoGAPs) whose expression is frequently down-regulated or silenced in a
      variety of human malignancies. The RhoGAP activity is required for full DLC
      dependent tumor suppressor activity. Here we report that DLC1 and DLC3 bind to
      human tensin1 and its chicken homolog. The binding has been mapped to the tensin
      Src homology 2 (SH2) and phosphotyrosine binding (PTB) domains at the C terminus
      of tensin proteins. Distinct DLC1 sequences are required for SH2 and PTB binding.
      DCL binding to both domains is constitutive under basal conditions. The SH2
      binding depends on a tyrosine in DCL1 (Y442) but is phosphotyrosine-independent,
      a highly unusual feature for SH2 binding. DLC1 competed with the binding of other
      proteins to the tensin C terminus, including beta 3-integrin binding to the PTB
      domain. Point mutation of a critical tyrosine residue (Y442F) in DLC1 rendered
      the protein deficient for binding the tensin SH2 domain and binding full-length
      tensin. The Y442F protein was diffusely cytoplasmic, in contrast to the
      localization of wild-type DLC1 to focal adhesions, but it retained the ability to
      reduce the intracellular levels of Rho-GTP. The Y442F mutant displayed markedly
      reduced biological activity, as did a mutant that was RhoGAP-deficient. The
      results suggest that DLC1 is a multifunctional protein whose biological activity
      depends on cooperation between its tensin binding and RhoGAP activities, although
      neither activity depends on the other.

PMID- 17517631
TI  - Sequential structures provide insights into the fidelity of RNA replication.
AB  - RNA virus replication is an error-prone event caused by the low fidelity of viral
      RNA-dependent RNA polymerases. Replication fidelity can be decreased further by
      the use of mutagenic ribonucleoside analogs to a point where viral genetic
      information can no longer be maintained. For foot-and-mouth disease virus, the
      antiviral analogs ribavirin and 5-fluorouracil have been shown to be mutagenic,
      contributing to virus extinction through lethal mutagenesis. Here, we report the
      x-ray structure of four elongation complexes of foot-and-mouth disease virus
      polymerase 3D obtained in presence of natural substrates, ATP and UTP, or
      mutagenic nucleotides, ribavirin triphosphate and 5-fluorouridine triphosphate
      with different RNAs as template-primer molecules. The ability of these complexes
      to synthesize RNA in crystals allowed us to capture different successive
      replication events and to define the critical amino acids involved in (i) the
      recognition and positioning of the incoming nucleotide or analog; (ii) the
      positioning of the acceptor base of the template strand; and (iii) the
      positioning of the 3'-OH group of the primer nucleotide during RNA replication.
      The structures identify key interactions involved in viral RNA replication and
      provide insights into the molecular basis of the low fidelity of viral RNA
      polymerases.

PMID- 17517632
TI  - Experimental observation of quantum oscillation of surface chemical reactivities.
AB  - Here we present direct observation of a quantum reactivity with respect to the
      amounts of O(2) adsorbed and the rates of surface oxidation as a function of film
      thickness on ultrathin (2-6 nm) Pb mesas by scanning tunneling microscopy.
      Simultaneous spectroscopic measurements on the electronic structures reveal a
      quantum oscillation that originates from quantum well states of the mesas, as a
      generalization of the Fabry-Perot modes of confined electron waves. We expect the
      quantum reactivity to be a general phenomenon for most ultrathin metal films with
      broad implications, such as nanostructure tuning of surface reactivities and
      rational design of heterogeneous catalysts.

PMID- 17517633
TI  - Cryptic speciation in a model invertebrate chordate.
AB  - We applied independent species concepts to clarify the phylogeographic structure
      of the ascidian Ciona intestinalis, a powerful model system in chordate biology
      and for comparative genomic studies. Intensive research with this marine
      invertebrate is based on the assumption that natural populations globally belong
      to a single species. Therefore, understanding the true taxonomic classification
      may have implications for experimental design and data management. Phylogenies
      inferred from mitochondrial and nuclear DNA markers accredit the existence of two
      cryptic species: C. intestinalis sp. A, genetically homogeneous, distributed in
      the Mediterranean, northeast Atlantic, and Pacific, and C. intestinalis sp. B,
      geographically structured and encountered in the North Atlantic. Species-level
      divergence is further entailed by cross-breeding estimates. C. intestinalis A and
      B from allopatric populations cross-fertilize, but hybrids remain infertile
      because of defective gametogenesis. Although anatomy illustrates an overall
      interspecific similarity lacking in diagnostic features, we provide consistent
      tools for in-field and in-laboratory species discrimination. Finding of two
      cryptic taxa in C. intestinalis raises interest in a new tunicate genome as a
      gateway to studies in speciation and ecological adaptation of chordates.

PMID- 17517634
TI  - Evolutionary and geographical history of the Leishmania donovani complex with a
      revision of current taxonomy.
AB  - Leishmaniasis is a geographically widespread severe disease, with an increasing
      incidence of two million cases per year and 350 million people from 88 countries
      at risk. The causative agents are species of Leishmania, a protozoan flagellate.
      Visceral leishmaniasis, the most severe form of the disease, lethal if untreated,
      is caused by species of the Leishmania donovani complex. These species are
      morphologically indistinguishable but have been identified by molecular methods,
      predominantly multilocus enzyme electrophoresis. We have conducted a
      multifactorial genetic analysis that includes DNA sequences of protein-coding
      genes as well as noncoding segments, microsatellites, restriction-fragment length
      polymorphisms, and randomly amplified polymorphic DNAs, for a total of
      approximately 18,000 characters for each of 25 geographically representative
      strains. Genotype is strongly correlated with geographical (continental) origin,
      but not with current taxonomy or clinical outcome. We propose a new taxonomy, in
      which Leishmania infantum and L. donovani are the only recognized species of the
      L. donovani complex, and we present an evolutionary hypothesis for the origin and
      dispersal of the species. The genus Leishmania may have originated in South
      America, but diversified after migration into Asia. L. donovani and L. infantum
      diverged approximately 1 Mya, with further divergence of infraspecific genetic
      groups between 0.4 and 0.8 Mya. The prevailing mode of reproduction is clonal,
      but there is evidence of genetic exchange between strains, particularly in
      Africa.

PMID- 17517635
TI  - High-resolution scanning tunneling microscopy imaging of mesoscopic graphene
      sheets on an insulating surface.
AB  - We present scanning tunneling microscopy (STM) images of single-layer graphene
      crystals examined under ultrahigh vacuum conditions. The samples, with lateral
      dimensions on the micrometer scale, were prepared on a silicon dioxide surface by
      direct exfoliation of crystalline graphite. The single-layer films were
      identified by using Raman spectroscopy. Topographic images of single-layer
      samples display the honeycomb structure expected for the full hexagonal symmetry
      of an isolated graphene monolayer. The absence of observable defects in the STM
      images is indicative of the high quality of these films. Crystals composed of a
      few layers of graphene also were examined. They exhibited dramatically different
      STM topography, displaying the reduced threefold symmetry characteristic of the
      surface of bulk graphite.

PMID- 17517636
TI  - Collapse of a fish population after exposure to a synthetic estrogen.
AB  - Municipal wastewaters are a complex mixture containing estrogens and estrogen
      mimics that are known to affect the reproductive health of wild fishes. Male
      fishes downstream of some wastewater outfalls produce vitellogenin (VTG) (a
      protein normally synthesized by females during oocyte maturation) and early-stage
      eggs in their testes, and this feminization has been attributed to the presence
      of estrogenic substances such as natural estrogens [estrone or 17beta-estradiol
      (E2)], the synthetic estrogen used in birth-control pills [17 alpha
      ethynylestradiol (EE2)], or weaker estrogen mimics such as nonylphenol in the
      water. Despite widespread evidence that male fishes are being feminized, it is
      not known whether these low-level, chronic exposures adversely impact the
      sustainability of wild populations. We conducted a 7-year, whole-lake experiment
      at the Experimental Lakes Area (ELA) in northwestern Ontario, Canada, and showed
      that chronic exposure of fathead minnow (Pimephales promelas) to low
      concentrations (5-6 ng x L(-1)) of the potent 17 alpha-ethynylestradiol led to
      feminization of males through the production of vitellogenin mRNA and protein,
      impacts on gonadal development as evidenced by intersex in males and altered
      oogenesis in females, and, ultimately, a near extinction of this species from the
      lake. Our observations demonstrate that the concentrations of estrogens and their
      mimics observed in freshwaters can impact the sustainability of wild fish
      populations.

PMID- 17517637
TI  - Acoustic mimicry in a predator-prey interaction.
AB  - Mimicry of visual warning signals is one of the keystone concepts in evolutionary
      biology and has received substantial research attention. By comparison, acoustic
      mimicry has never been rigorously tested. Visualizing bat-moth interactions with
      high-speed, infrared videography, we provide empirical evidence for acoustic
      mimicry in the ultrasonic warning sounds that tiger moths produce in response to
      echolocating bats. Two species of sound-producing tiger moths were offered
      successively to naive, free-flying red and big brown bats. Noctuid and pyralid
      moth controls were also offered each night. All bats quickly learned to avoid the
      noxious tiger moths first offered to them, associating the warning sounds with
      bad taste. They then avoided the second sound-producing species regardless of
      whether it was chemically protected or not, verifying both Mullerian and Batesian
      mimicry in the acoustic modality. A subset of the red bats subsequently
      discovered the palatability of the Batesian mimic, demonstrating the powerful
      selective force these predators exert on mimetic resemblance. Given these results
      and the widespread presence of tiger moth species and other sound-producing
      insects that respond with ultrasonic clicks to bat attack, acoustic mimicry
      complexes are likely common components of the acoustic landscape.

PMID- 17517638
TI  - Combination brain and systemic injections of AAV provide maximal functional and
      survival benefits in the Niemann-Pick mouse.
AB  - Niemann-Pick disease (NPD) is caused by the loss of acid sphingomyelinase (ASM)
      activity, which results in widespread accumulation of undegraded lipids in cells
      of the viscera and CNS. In this study, we tested the effect of combination brain
      and systemic injections of recombinant adeno-associated viral vectors encoding
      human ASM (hASM) in a mouse model of NPD. Animals treated by combination therapy
      exhibited high levels of hASM in the viscera and brain, which resulted in near
      complete correction of storage throughout the body. This global reversal of
      pathology translated to normal weight gain and superior recovery of motor and
      cognitive functions compared to animals treated by either brain or systemic
      injection alone. Furthermore, animals in the combination group did not generate
      antibodies to hASM, demonstrating the first application of systemic-mediated
      tolerization to improve the efficacy of brain injections. All of the animals
      treated by combination therapy survived in good health to an investigator
      selected 54 weeks, whereas the median lifespans of the systemic-alone, brain
      alone, or untreated ASM knockout groups were 47, 48, and 34 weeks, respectively.
      These data demonstrate that combination therapy is a promising therapeutic
      modality for treating NPD and suggest a potential strategy for treating disease
      indications that cause both visceral and CNS pathologies.

PMID- 17517639
TI  - Early sorting of inner nuclear membrane proteins is conserved.
AB  - Spodoptera frugiperda (Sf9) importin-alpha-16 is a translocon-associated protein
      that participates in the early sorting pathway of baculovirus integral membrane
      proteins destined for the inner nuclear membrane (INM). To discern whether
      sorting intermediate protein complexes like those observed in insect cells are
      also formed with mammalian INM proteins, cross-linked complexes of importin-alpha
      16 with human lamin B receptor (LBR) and nurim were examined. Both LBR and nurim
      cross-link with Sf9 importin-alpha-16 during cotranslational membrane integration
      and remain proximal with importin-alpha-16 after integration into the endoplasmic
      reticulum membrane and release from the translocon. Human cells encode several
      isoforms of importin-alpha; to determine whether any of these isoforms may
      recognize INM-directed proteins, they were tested for their ability to cross-link
      with the viral-derived INM sorting motif sequence. One cross-linked adduct was
      detected with a 16-kDa isoform encoded from KPNA4 (KPNA-4-16). KPNA-4-16 was
      easily detected in microsomal membranes prepared from KPNA4-16 recombinant virus
      infected cells and was also detected in microsomes prepared from HeLa cells.
      Together these observations suggest that elements of the early sorting pathway of
      INM-directed proteins mediated by importin-alpha-16 are highly conserved, and
      mammalian KPNA-4-16 is a candidate partner in sorting integral membrane proteins
      to the INM.

PMID- 17517640
TI  - Tropical birds have a slow pace of life.
AB  - Tropical birds are relatively long-lived and produce few offspring, which develop
      slowly and mature relatively late in life, the slow end of the life-history axis,
      whereas temperate birds lie at the opposite end of this continuum. We tested the
      hypothesis that tropical birds have evolved a reduced basal metabolic rate (BMR).
      We measured BMR of 69 species of tropical birds, the largest data set amassed on
      metabolic rates of tropical birds, and compared these measurements with 59
      estimates of BMR for temperate birds. Our analyses included conventional least
      squares regression, regressions based on phylogenetic independent contrasts, and
      a comparison of BMR of 13 phylogenetically matched pairs, one species from the
      tropics and one from northerly temperate areas. Our triptych showed that tropical
      birds had a reduced BMR, compelling evidence for a connection between the life
      history of tropical birds and a slow pace of life. Further, tropical migrants
      breeding in temperate habitats had a lower BMR than did temperate residents,
      suggesting that these migrants have physiological traits consistent with a slow
      pace of life. In addition, we determined that tropical birds had a lower cold
      induced peak metabolic rate and thermogenic metabolic scope than temperate
      species, a finding that is consistent with the hypothesis that their environment
      has not selected for high levels of thermogenesis, or alternatively, that a slow
      pace of life may be incompatible with high thermogenic capacity. We conclude that
      physiological function correlates with the suite of life-history traits.

PMID- 17517641
TI  - Characterization of actomyosin bond properties in intact skeletal muscle by force
      spectroscopy.
AB  - Force generation and motion in skeletal muscle result from interaction between
      actin and myosin myofilaments through the cyclical formation and rupture of the
      actomyosin bonds, the cross-bridges, in the overlap region of the sarcomeres.
      Actomyosin bond properties were investigated here in single intact muscle fibers
      by using dynamic force spectroscopy. The force needed to forcibly detach the
      cross-bridge ensemble in the half-sarcomere (hs) was measured in a range of
      stretching velocity between 3.4 x 10(3) nm.hs(-1).s(-1) or 3.3 fiber length per
      second (l(0)s(-1)) and 6.1 x 10(4) nm.hs(-1).s(-1) or 50 l(0).s(-1) during
      tetanic force development. The rupture force of the actomyosin bond increased
      linearly with the logarithm of the loading rate, in agreement with previous
      experiments on noncovalent single bond and with Bell theory [Bell GI (1978)
      Science 200:618-627]. The analysis permitted calculation of the actomyosin
      interaction length, x(beta) and the dissociation rate constant for zero external
      load, k(0). Mean x(beta) was 1.25 nm, a value similar to that reported for single
      actomyosin bond under rigor condition. Mean k(0) was 20 s(-1), a value about
      twice as great as that reported in the literature for isometric force relaxation
      in the same type of muscle fibers. These experiments show, for the first time,
      that force spectroscopy can be used to reveal the properties of the individual
      cross-bridge in intact skeletal muscle fibers.

PMID- 17517642
TI  - Artificial selection of simulated microbial ecosystems.
AB  - Recent work with microbial communities has demonstrated an adaptive response to
      artificial selection at the level of the ecosystem. The reasons for this response
      and the level at which adaptation occurs are unclear: does selection act
      implicitly on traits of individual species, or are higher-level traits genuinely
      being selected? If the ecosystem response is just the additive combination of the
      responses of the constituent species, then the ecosystem response could be
      predicted a priori, and the ecosystem-level selection process is superfluous.
      However, if the ecosystem response results from ecological interactions among
      species, then selection at a higher level is necessary. Here we perform
      artificial ecosystem selection experiments on an individual-based evolutionary
      simulation model of microbial ecology and observe a similar response to that seen
      with real ecosystems. We demonstrate that a significant fraction of artificially
      selected ecosystem responses cannot be accounted for by implicit lower-level
      selection of a single type of organism within the community, and that
      interactions among different types of organism contribute significantly to the
      response in the majority of cases. However, when the ecological problem posed by
      the artificial ecosystem selection process can be easily solved by a single
      dominant species, it often is.

PMID- 17517643
TI  - Age-related changes in adaptation to severe anemia in childhood in developing
      countries.
AB  - Severe forms of anemia in children in the developing countries may be
      characterized by different clinical manifestations at particular stages of
      development. Whether this reflects developmental changes in adaptation to anemia
      or other mechanisms is not clear. The pattern of adaptation to anemia has been
      assessed in 110 individuals with hemoglobin (Hb) E beta-thalassemia, one of the
      commonest forms of inherited anemia in Asia. It has been found that age and Hb
      levels are independent variables with respect to erythropoietin response and that
      there is a decline in the latter at a similar degree of anemia during
      development. To determine whether this finding is applicable to anemia due to
      other causes, a similar study has been carried out on 279 children with severe
      anemia due to Plasmodium falciparum malaria; the results were similar to those in
      the patients with thalassemia. These observations may have important implications
      both for the better understanding of the pathophysiology of profound anemia in
      early life and for its more logical and cost-effective management.

PMID- 17517644
TI  - Inhibitor of growth 4 (ING4) is up-regulated by a low K intake and suppresses
      renal outer medullary K channels (ROMK) by MAPK stimulation.
AB  - Dietary K intake plays an important role in the regulation of renal K secretion:
      a high K intake stimulates whereas low K intake suppresses renal K secretion. Our
      previous studies demonstrated that the Src family protein-tyrosine kinase and
      mitogen-activated protein kinase (MAPK) are involved in mediating the effect of
      low K intake on renal K channels and K secretion. However, the molecular
      mechanism by which low K intake stimulates MAPK is not completely understood.
      Here we show that inhibitor of growth 4 (ING4), a protein with a highly conserved
      plant homeodomain finger motif, is involved in mediating the effect of low K
      intake on MAPK. K restriction stimulates the expression of ING4 in the kidney and
      superoxide anions, and its related products are involved in mediating the effect
      of low K intake on ING4 expression. We used HEK293 cells to express ING4 and
      observed that expression of ING4 increased the phosphorylation of p38 and ERK
      MAPK, whereas down-regulation of ING4 with small interfering RNA decreased the
      phosphorylation of p38 and ERK. Immunocytochemistry showed that ING4 was
      expressed in the renal outer medullary potassium (ROMK)-positive tubules.
      Moreover, ING4 decreased K currents in Xenopus oocytes injected with ROMK channel
      cRNA. This inhibitory effect was reversed by blocking p38 and ERK MAPK. These
      data provide evidence for the role of ING4 in mediating the effect of low K
      intake on ROMK channel activity by stimulation of p38 and ERK MAPK.

PMID- 17517645
TI  - Polarity reveals intrinsic cell chirality.
AB  - Like blood neutrophils, dHL60 cells respond to a uniform concentration of
      attractant by polarizing in apparently random directions. How each cell chooses
      its own direction is unknown. We now find that an arrow drawn from the center of
      the nucleus of an unpolarized cell to its centrosome strongly predicts the
      subsequent direction of attractant-induced polarity: Of 60 cells that polarized
      in response to uniform f-Met-Leu-Phe (fMLP), 42 polarized to the left of this
      arrow, 6 polarized to the right, and 12 polarized directly toward or away from
      the centrosome. To investigate this directional bias we perturbed a regulatory
      pathway, downstream of Cdc42 and partitioning-defective 6 (Par6), which controls
      centrosome orientation relative to polarity of other cells. Dominant negative
      Par6 mutants block polarity altogether, as previously shown for disrupting Cdc42
      activity. Cells remain able to polarize, but without directional bias, if their
      microtubules are disrupted with nocodazole, or they express mutant proteins that
      interfere with activities of PKCzeta or dynein. Expressing constitutively active
      glycogen synthase kinase 3beta (GSK3beta) causes cells to polarize preferentially
      to the right. Distributions of most of these polarity regulators localize to the
      centrosome but show no left-right asymmetry before polarization. Together, these
      findings suggest that an intrinsically chiral structure, perhaps the centrosome,
      serves as a template for directing polarity in the absence of spatial cues. Such
      a template could help to determine left-right asymmetry and planar polarity in
      development.

PMID- 17517646
TI  - Vitamin D receptor is essential for normal keratinocyte stem cell function.
AB  - The major physiological role of the vitamin D receptor (VDR) is the maintenance
      of mineral ion homeostasis. Mutation of the VDR, in humans and mice, results in
      alopecia. Unlike the effects of the VDR on mineral ion homeostasis, the actions
      of the VDR that prevent alopecia are ligand-independent. Although absence of the
      VDR does not prevent the development of a keratinocyte stem cell niche in the
      bulge region of the hair follicle, it results in an inability of these stem cells
      to regenerate the lower portion of the hair follicle in vivo and impairs
      keratinocyte stem cell colony formation in vitro. VDR ablation is associated with
      a gradual decrease in keratinocyte stem cells, accompanied by an increase in
      sebaceous activity, a phenotype analogous to that seen with impaired canonical
      Wnt signaling. Transient gene expression assays demonstrate that the cooperative
      transcriptional effects of beta-catenin and Lef1 are abolished in keratinocytes
      isolated from VDR-null mice, revealing a role for the unliganded VDR in canonical
      Wnt signaling. Thus, absence of the VDR impairs canonical Wnt signaling in
      keratinocytes and leads to the development of alopecia due to a defect in
      keratinocyte stem cells.

PMID- 17517647
TI  - Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic
      steatosis and diet-induced obesity.
AB  - The mammalian circadian system consists of a central oscillator in the
      suprachiasmatic nucleus of the hypothalamus, which coordinates peripheral clocks
      in organs throughout the body. Although circadian clocks control the rhythmic
      expression of a large number of genes involved in metabolism and other aspects of
      circadian physiology, the consequences of genetic disruption of circadian
      controlled pathways remain poorly defined. Here we report that the targeted
      disruption of Nocturnin (Ccrn4l) in mice, a gene that encodes a circadian
      deadenylase, confers resistance to diet-induced obesity. Mice lacking Nocturnin
      remain lean on high-fat diets, with lower body weight and reduced visceral fat.
      However, unlike lean lipodystrophic mouse models, these mice do not have fatty
      livers and do not exhibit increased activity or reduced food intake. Gene
      expression data suggest that Nocturnin knockout mice have deficits in lipid
      metabolism or uptake, in addition to changes in glucose and insulin sensitivity.
      Our data support a pivotal role for Nocturnin downstream of the circadian
      clockwork in the posttranscriptional regulation of genes necessary for nutrient
      uptake, metabolism, and storage.

PMID- 17517648
TI  - Multigene amplification and massively parallel sequencing for cancer mutation
      discovery.
AB  - We have developed a procedure for massively parallel resequencing of multiple
      human genes by combining a highly multiplexed and target-specific amplification
      process with a high-throughput parallel sequencing technology. The amplification
      process is based on oligonucleotide constructs, called selectors, that guide the
      circularization of specific DNA target regions. Subsequently, the circularized
      target sequences are amplified in multiplex and analyzed by using a highly
      parallel sequencing-by-synthesis technology. As a proof-of-concept study, we
      demonstrate parallel resequencing of 10 cancer genes covering 177 exons with
      average sequence coverage per sample of 93%. Seven cancer cell lines and one
      normal genomic DNA sample were studied with multiple mutations and polymorphisms
      identified among the 10 genes. Mutations and polymorphisms in the TP53 gene were
      confirmed by traditional sequencing.

PMID- 17517649
TI  - Broadly neutralizing anti-hepatitis B virus antibody reveals a complementarity
      determining region H3 lid-opening mechanism.
AB  - The humanized monoclonal antibody HzKR127 recognizes the preS1 domain of the
      human hepatitis B virus surface proteins with a broadly neutralizing activity in
      vivo. We present the crystal structures of HzKR127 Fab and its complex with a
      major epitope peptide. In the complex structure, the bound peptide forms a type
      IV beta-turn followed by 3(10) helical turn, the looped-out conformation of which
      provides a structural basis for broad neutralization. Upon peptide binding, the
      antibody undergoes a dramatic complementarity determining region H3 lid opening.
      To understand the structural implication of the virus neutralization, we carried
      out comprehensive alanine-scanning mutagenesis of all complementarity determining
      region residues in HzKR127 Fab. The functional mapping of the antigen-combining
      site demonstrates the specific roles of major binding determinants in antigen
      binding, contributing to the rational design for maximal humanization and
      affinity maturation of the antibody.

PMID- 17517650
TI  - Functional identification of the hematopoietic stem cell niche in the ventral
      domain of the embryonic dorsal aorta.
AB  - The first definitive/adult-type hematopoietic stem cells (HSCs) in the mouse
      aorta-gonad-mesonephros region emerge between embryonic days 10.5 and 11.5. The
      discovery of clusters of hematopoietic cells on the ventral luminal surface of
      the dorsal aorta in various vertebrate species has led to speculation that the
      floor of the dorsal aorta may play an essential role for the development of the
      definitive hematopoietic system. Here, we functionally show affiliation of
      definitive HSCs with the ventral floor of the dorsal aorta, whereas colony
      forming hematopoietic activity is associated with both ventral and dorsal
      domains. We show that a rare population of PECAM1(high)CD45(+) cells, within
      which definitive HSCs reside, is predominantly localized to intraaortic clusters.
      Furthermore, using ex vivo culture analysis, we demonstrate that the ventral
      domain of the dorsal aorta has an exclusive functional capacity of inducing and
      expanding definitive HSCs.

PMID- 17517651
TI  - Interaction between innate immune cells and a bacterial type III secretion system
      in mutualistic and pathogenic associations.
AB  - Animals house a community of bacterial symbionts in their digestive tracts that
      contribute to their well being. The medicinal leech, Hirudo verbana, has a
      remarkably simple gut population carrying two extracellular microbes in the crop
      where the ingested blood is stored. This simplicity renders it attractive for
      studying colonization factors. Aeromonas veronii, one of the leech symbionts, can
      be genetically manipulated and is a pathogen of mammals. Screening transposon
      mutants of A. veronii for colonization defects in the leech, we found one mutant,
      JG752, with a transposon insertion in an ascU homolog, encoding an essential
      component of type III secretion systems (T3SS). Competing JG752 against the wild
      type revealed that JG752 was increasingly attenuated over time (10-fold at 18 h
      and >10,000-fold at 96 h). This colonization defect was linked to ascU by
      complementing JG752 with the operon containing ascU. Fluorescence in situ
      hybridization analysis revealed that at 42 h 38% of JG752 cells were phagocytosed
      by leech macrophage-like cells compared with <0.1% of the parental strain. Using
      mammalian macrophages, a lactate dehydrogenase release assay revealed that
      cytotoxicity was significantly reduced in macrophages exposed to JG752. In a
      mouse septicemia model, JG752 killed only 30% of mice, whereas the parent strain
      killed 100%, showing the importance of T3SS for both pathogenesis and mutualism.
      Phagocytic immune cells are important not only in defending against pathogens but
      also in maintaining the mutualistic symbiont community inside the leech,
      demonstrating that animals use similar, conserved mechanisms to control bacterial
      populations, even when the outcomes differ dramatically.

PMID- 17517652
TI  - A sperm-specific Na+/H+ exchanger (sNHE) is critical for expression and in vivo
      bicarbonate regulation of the soluble adenylyl cyclase (sAC).
AB  - We previously identified a sperm-specific Na(+)/H(+) exchanger (sNHE) principally
      localized to the flagellum. Disruption of the sNHE gene in mice resulted in
      absolute male infertility associated with a complete loss of sperm motility.
      Here, we show that the sNHE-null spermatozoa fail to develop the cAMP-dependent
      protein tyrosine phosphorylation that coincides with the functional maturation
      occurring upon incubation in capacitating conditions in vitro. Both the sperm
      motility defect and the lack of induced protein tyrosine phosphorylation are
      rescued by the addition of cell-permeable cAMP analogs, suggesting that cAMP
      metabolism is impaired in spermatozoa lacking sNHE. Our analyses of the
      bicarbonate-dependent soluble adenylyl cyclase (sAC) signaling pathway in sNHE
      null sperm cells reveal that sNHE is required for the expression of full-length
      sAC, and that it is important for the bicarbonate stimulation of sAC activity in
      spermatozoa. Furthermore, both codependent expression and coimmunoprecipitation
      experiments indicate that sNHE and sAC associate with each other. Thus, these two
      proteins appear to be components of a signaling complex at the sperm flagellar
      plasma membrane. We propose that the formation of this complex efficiently
      modulates intracellular pH and bicarbonate levels through the rapid and effective
      control of sAC and sNHE activities to facilitate sperm motility regulation.

PMID- 17517653
TI  - A genome-wide RNA interference screen identifies putative chromatin regulators
      essential for E2F repression.
AB  - Regulation of chromatin structure is critical in many fundamental cellular
      processes. Previous studies have suggested that the Rb tumor suppressor may
      recruit multiple chromatin regulatory proteins to repress E2F, a key regulator of
      cell proliferation and differentiation. Taking advantage of the evolutionary
      conservation of the E2F pathway, we have conducted a genome-wide RNAi screen in
      cultured Drosophila cells for genes required for repression of E2F activity.
      Among the genes identified are components of the putative Domino chromatin
      remodeling complex, as well as the Polycomb Group (PcG) protein-like fly tumor
      suppressor, L3mbt, and the related CG16975/dSfmbt. These factors are recruited to
      E2F-responsive promoters through physical association with E2F and are required
      for repression of endogenous E2F target genes. Surprisingly, their inhibitory
      activities on E2F appear to be independent of Rb. In Drosophila, domino mutation
      enhances cell proliferation induced by E2F overexpression and suppresses a loss
      of-function cyclin E mutation. These findings suggest that potential chromatin
      regulation mediated by Domino and PcG-like factors plays an important role in
      controlling E2F activity and cell growth.

PMID- 17517654
TI  - Ultra-small-sample molecular structure detection using microslot waveguide
      nuclear spin resonance.
AB  - We here report on the design of a planar microslot waveguide NMR probe with an
      induction element that can be fabricated at scales from centimeters to nanometers
      to allow analysis of biomolecules at nano- or picomole quantities, reducing the
      required amount of materials by several orders of magnitude. This device
      demonstrates the highest signal-to-noise ratio for a planar detector to date,
      measured by using the anomeric proton signal from a 15.6-nmol sample of sucrose.
      This probe had a linewidth of 1.1 Hz for pure water without susceptibility
      matching. Analysis of 1.57 nmol of ribonuclease-A shows high sensitivity in one-
      and two-dimensional NMR spectra. Along with reducing required sample volumes,
      this integrated geometry can be packed in parallel arrays and combined with
      microfluidic systems. Further development of this device may have broad
      implications not only for advancing our understanding of many intractable protein
      structures and their folding, molecular interactions, and dynamic behaviors, but
      also for high-sensitivity diagnosis of a number of protein conformational
      diseases.

PMID- 17517655
TI  - Mechanism of histone methylation catalyzed by protein lysine methyltransferase
      SET7/9 and origin of product specificity.
AB  - Methylation of certain lysine residues in the N-terminal tails of core histone
      proteins in nucleosome is of fundamental importance in the regulation of
      chromatin structure and gene expression. Such histone modification is catalyzed
      by protein lysine methyltransferases (PKMTs). PKMTs contain a conserved SET
      domain in almost all of the cases and may transfer one to three methyl groups
      from S-adenosyl-L-methionine (AdoMet) to the epsilon-amino group of the target
      lysine residue. Here, quantum mechanical/molecular mechanical molecular dynamics
      and free-energy simulations are performed on human PKMT SET7/9 and its mutants to
      understand two outstanding questions for the reaction catalyzed by PKMTs: the
      mechanism for deprotonation of positively charged methyl lysine (lysine) and
      origin of product specificity. The results of the simulations suggest that Tyr
      335 (an absolute conserved residue in PKMTs) may play the role as the general
      base for the deprotonation after dissociation of AdoHcy (S-adenosyl-L
      homocysteine) and before binding of AdoMet. It is shown that conformational
      changes could bring Y335 to the target methyl lysine (lysine) for proton
      abstraction. This mechanism provides an explanation why methyl transfers could be
      catalyzed by PKMTs processively. The free-energy profiles for methyl transfers
      are reported and analyzed for wild type and certain mutants (Y305F and Y335F) and
      the active-site interactions that are of importance for the enzyme's function are
      discussed. The results of the simulations provide important insights into the
      catalytic process and lead to a better understanding of experimental observations
      concerning the origin of product specificity for PKMTs.

PMID- 17517656
TI  - Polymerization kinetics of ADP- and ADP-Pi-actin determined by fluorescence
      microscopy.
AB  - We used fluorescence microscopy to determine how polymerization of Mg-ADP-actin
      depends on the concentration of phosphate. From the dependence of the elongation
      rate on the actin concentration and direct observations of depolymerizing
      filaments, we measured the polymerization rate constants of ADP-actin and ADP
      P(i)-actin. Saturating phosphate reduces the critical concentration for
      polymerization of Mg-ADP-actin from 1.8 to 0.06 microM almost entirely by
      reducing the dissociation rate constants at both ends. Saturating phosphate
      increases the barbed end association rate constant of Mg-ADP-actin 15%, but this
      value is still threefold less than that of ATP-actin. Thus, ATP hydrolysis
      without phosphate dissociation must change the conformation of polymerized actin.
      Analysis of depolymerization experiments in the presence of phosphate suggests
      that phosphate dissociation near the terminal subunits is much faster than in the
      interior. Remarkably, 10 times more phosphate is required to slow the
      depolymerization of the pointed end than the barbed end, suggesting a weak
      affinity of phosphate near the pointed end. Our observations of single actin
      filaments provide clues about the origins of the difference in the critical
      concentration at the two ends of actin filaments in the presence of ATP.

PMID- 17517657
TI  - Chromosome instability, chromosome transcriptome, and clonal evolution of tumor
      cell populations.
AB  - Chromosome instability and aneuploidy are hallmarks of cancer, but it is not
      clear how changes in the chromosomal content of a cell contribute to the
      malignant phenotype. Previously we have shown that we can readily isolate highly
      proliferative tumor cells and their revertants from highly invasive tumor cell
      populations, indicating how phenotypic shifting can contribute to malignant
      progression. Here we show that chromosome instability and changes in chromosome
      content occur with phenotypic switching. Further, we show that changes in the
      copy number of each chromosome quantitatively impose a proportional change in the
      chromosome transcriptome ratio. This correlation also applies to subchromosomal
      regions of derivative chromosomes. Importantly, we show that the changes in
      chromosome content and the transcriptome favor the expression of a large number
      of genes appropriate for the specific tumor phenotype. We conclude that
      chromosome instability generates the necessary chromosome diversity in the tumor
      cell populations and, therefore, the transcriptome diversity to allow for
      environment-facilitated clonal expansion and clonal evolution of tumor cell
      populations.

PMID- 17517658
TI  - Stress response during development predicts fitness in a wild, long lived
      vertebrate.
AB  - Short-term elevation of circulating glucocorticosteroids (GCs) in vertebrates
      facilitates the adoption of a distinct emergency life history state, which allows
      individuals to cope with perturbations and recover homeostasis at the expense of
      temporarily suppressing nonessential activities. Although GC responses are viewed
      as a major evolutionary mechanism to maximize fitness through stress management,
      phenotypic variability exists within animal populations, and it remains unclear
      whether interindividual differences in stress physiology can explain variance in
      unequivocal components of fitness. We show that the magnitude of the
      adrenocortical response to a standardized perturbation during development is
      negatively related to survival and recruitment in a wild population of long lived
      birds. Our results provide empirical evidence for a link between stress response,
      not exposure to stressors, and fitness in a vertebrate under natural conditions.
      Recent studies suggest that variability in the adrenocortical response to stress
      may be maintained if high and low GC responders represent alternative coping
      strategies, with differential adaptive value depending on environmental
      conditions. Increased fitness among low GC responders, having a proactive
      personality, is predicted under elevated population density and availability of
      food resources, conditions that characterize our study population.

PMID- 17517659
TI  - Metabolic targeting of hypoxia and HIF1 in solid tumors can enhance cytotoxic
      chemotherapy.
AB  - Solid tumors frequently contain large regions with low oxygen concentrations
      (hypoxia). The hypoxic microenvironment induces adaptive changes to tumor cell
      metabolism, and this alteration can further distort the local microenvironment.
      The net result of these tumor-specific changes is a microenvironment that
      inhibits many standard cytotoxic anticancer therapies and predicts for a poor
      clinical outcome. Pharmacologic targeting of the unique metabolism of solid
      tumors could alter the tumor microenvironment to provide more favorable
      conditions for anti-tumor therapy. Here, we describe a strategy in which the
      mitochondrial metabolism of tumor cells is increased by pharmacologic inhibition
      of hypoxia-inducible factor 1 (HIF1) or its target gene pyruvate dehydrogenase
      kinase 1 (PDK1). This acute increase in oxygen consumption leads to a
      corresponding decrease in tumor oxygenation. Whereas decreased oxygenation could
      reduce the effectiveness of some traditional therapies, we show that it
      dramatically increases the effectiveness of a hypoxia-specific cytotoxin. This
      treatment strategy should provide a high degree of tumor specificity for
      increasing the effectiveness of hypoxic cytotoxins, as it depends on the
      activation of HIF1 and the presence of hypoxia, conditions that are present only
      in the tumor, and not the normal tissue.

PMID- 17517660
TI  - NRAS mutation causes a human autoimmune lymphoproliferative syndrome.
AB  - The p21 RAS subfamily of small GTPases, including KRAS, HRAS, and NRAS, regulates
      cell proliferation, cytoskeletal organization, and other signaling networks, and
      is the most frequent target of activating mutations in cancer. Activating
      germline mutations of KRAS and HRAS cause severe developmental abnormalities
      leading to Noonan, cardio-facial-cutaneous, and Costello syndrome, but activating
      germline mutations of NRAS have not been reported. Autoimmune lymphoproliferative
      syndrome (ALPS) is the most common genetic disease of lymphocyte apoptosis and
      causes autoimmunity as well as excessive lymphocyte accumulation, particularly of
      CD4(-), CD8(-) alphabeta T cells. Mutations in ALPS typically affect CD95
      (Fas/APO-1)-mediated apoptosis, one of the extrinsic death pathways involving TNF
      receptor superfamily proteins, but certain ALPS individuals have no such
      mutations. We show here that the salient features of ALPS as well as a
      predisposition to hematological malignancies can be caused by a heterozygous
      germline Gly13Asp activating mutation of the NRAS oncogene that does not impair
      CD95-mediated apoptosis. The increase in active, GTP-bound NRAS augments
      RAF/MEK/ERK signaling, which markedly decreases the proapoptotic protein BIM and
      attenuates intrinsic, nonreceptor-mediated mitochondrial apoptosis. Thus,
      germline activating mutations in NRAS differ from other p21 Ras oncoproteins by
      causing selective immune abnormalities without general developmental defects. Our
      observations on the effects of NRAS activation indicate that RAS-inactivating
      drugs, such as farnesyltransferase inhibitors should be examined in human
      autoimmune and lymphocyte homeostasis disorders.

PMID- 17517661
TI  - Nonlinear relaxation dynamics in elastic networks and design principles of
      molecular machines.
AB  - Analyzing nonlinear conformational relaxation dynamics in elastic networks
      corresponding to two classical motor proteins, we find that they respond by well
      defined internal mechanical motions to various initial deformations and that
      these motions are robust against external perturbations. We show that this
      behavior is not characteristic for random elastic networks. However, special
      network architectures with such properties can be designed by evolutionary
      optimization methods. Using them, an example of an artificial elastic network,
      operating as a cyclic machine powered by ligand binding, is constructed.

PMID- 17517662
TI  - When the usual insulin is just not enough.

PMID- 17517663
TI  - Cultural hitchhiking on the wave of advance of beneficial technologies.
AB  - The wave-of-advance model was introduced to describe the spread of advantageous
      genes in a population. It can be adapted to model the uptake of any advantageous
      technology through a population, such as the arrival of neolithic farmers in
      Europe, the domestication of the horse, and the development of the wheel, iron
      tools, political organization, or advanced weaponry. Any trait that preexists
      alongside the advantageous one could be carried along with it, such as genetics
      or language, regardless of any intrinsic superiority. Decoupling of the
      advantageous trait from other "hitchhiking" traits depends on its adoption by the
      preexisting population. Here, we adopt a similar wave-of-advance model based on
      food production on a heterogeneous landscape with multiple populations. Two key
      results arise from geographic inhomogeneity: the "subsistence boundary," land so
      poor that the wave of advance is halted, and the temporary "diffusion boundary"
      where the wave cannot move into poorer areas until its gradient becomes
      sufficiently large. At diffusion boundaries, farming technology may pass to
      indigenous people already in those poorer lands, allowing their population to
      grow and resist encroachment by farmers. Ultimately, this adoption of technology
      leads to the halt in spread of the hitchhiking trait and establishment of a
      permanent "cultural boundary" between distinct cultures with equivalent
      technology.

PMID- 17517664
TI  - Structure of the Munc18c/Syntaxin4 N-peptide complex defines universal features
      of the N-peptide binding mode of Sec1/Munc18 proteins.
AB  - Sec1/Munc18 proteins (SM proteins) bind to soluble NSF attachment protein
      receptors (SNAREs) and play an essential role in membrane fusion. Divergent modes
      of regulation have been proposed for different SM proteins indicating that they
      can either promote or inhibit SNARE assembly. This is in part because of discrete
      modes of binding that have been described for various SM/SNARE complexes. One
      mode suggests that SM proteins bind only to Syntaxins (Stx) preventing SNARE
      assembly, whereas in another they facilitate SNARE assembly and bind to SNARE
      complexes. The mammalian cell surface SM protein Munc18c binds to an N-peptide in
      Stx4, and this is compatible with its interaction with SNARE complexes. Here we
      describe the crystal structure of Munc18c in complex with the Stx4 N-peptide.
      This structure shows remarkable similarity with a yeast complex indicating that
      the mode of binding, which can accommodate SNARE complexes, is highly conserved
      throughout evolution. Modeling reveals the presence of the N-peptide binding mode
      in most but not all yeast and mammalian SM/Stx pairs, suggesting that it has
      coevolved to fulfill a specific regulatory function. It is unlikely that the N
      peptide interaction alone accounts for the specificity in SM/SNARE binding,
      implicating other contact surfaces in this function. Together with other data,
      our results support a sequential two-state model for SM/SNARE binding involving
      an initial interaction via the Stx N-peptide, which somehow facilitates a second,
      more comprehensive interaction comprising other contact surfaces in both
      proteins.

PMID- 17517665
TI  - Multimerized T cell epitopes protect from experimental autoimmune diabetes by
      inducing dominant tolerance.
AB  - Immunotherapy by using multimerized self-peptides has demonstrated a clear
      protective effect on experimental models of autoimmune diseases. However, the
      mechanisms involved remain ill-defined. Here we have evaluated the therapeutic
      efficacy of multimerized self-peptides at the effector phase of autoimmune
      diabetes and examined their mechanisms of action. Diabetes was induced in rat
      insulin promoter-hemagglutinin (HA) mice expressing HA in pancreatic beta-cells
      by adoptive transfer of HA(110-119)-specific T helper 1 cells. Complete
      protection was provided by low doses of the HA 4-mer consisting of four
      covalently linked linear HA(107-119) peptides. In vivo, the 4-mer appeared to act
      directly on the pathogenic HA-specific T helper 1 cells and indirectly by
      activation/recruitment of lymphocytes with regulatory properties so that mice
      became resistant to a second transfer of diabetogenic T cells. This effect was
      associated with a recruitment of Foxp3(+) CD4 T cells around islets. Moreover, we
      show that dominant protection from autoimmunity was transferable by spleen cells,
      and that development of this regulatory population was crucially dependent on the
      lymphocytes from treated rat insulin promoter-HA mice. Thus, immunotherapy using
      multimerized epitopes emerges as a promising strategy in view of the current
      identification of self-epitopes that are major targets of the pathogenic CD4 T
      cell response in autoimmune diseases.

PMID- 17517666
TI  - The helix-turn-helix motif as an ultrafast independently folding domain: the
      pathway of folding of Engrailed homeodomain.
AB  - Helices 2 and 3 of Engrailed homeodomain (EnHD) form a helix-turn-helix (HTH)
      motif. This common motif is believed not to fold independently, which is the
      characteristic feature of a motif rather than a domain. But we found that the
      EnHD HTH motif is monomeric and folded in solution, having essentially the same
      structure as in full-length protein. It had a sigmoidal thermal denaturation
      transition. Both native backbone and local tertiary interactions were formed
      concurrently at 4 x 10(5) s(-1) at 25 degrees C, monitored by IR and fluorescence
      T-jump kinetics, respectively, the same rate constant as for the fast phase in
      the folding of EnHD. The HTH motif, thus, is an ultrafast-folding, natural
      protein domain. Its independent stability and appropriate folding kinetics
      account for the stepwise folding of EnHD, satisfy fully the criteria for an on
      pathway intermediate, and explain the changes in mechanism of folding across the
      homeodomain family. Experiments on mutated and engineered fragments of the parent
      protein with different probes allowed the assignment of the observed kinetic
      phases to specific events to show that EnHD is not an example of one-state
      downhill folding.

PMID- 17517667
TI  - Parasites alter community structure.
AB  - Parasites often play an important role in modifying the physiology and behavior
      of their hosts and may, consequently, mediate the influence hosts have on other
      components of an ecological community. Along the northern Atlantic coast of North
      America, the dominant herbivorous snail Littorina littorea structures rocky
      intertidal communities through strong grazing pressure and is frequently
      parasitized by the digenean trematode Cryptocotyle lingua. We hypothesized that
      the effects of parasitism on host physiology would induce behavioral changes in
      L. littorea, which in turn would modulate L. littorea's influence on intertidal
      community composition. Specifically, we hypothesized that C. lingua infection
      would alter the grazing rate of L. littorea and, consequently, macroalgal
      communities would develop differently in the presence of infected versus
      uninfected snails. Our results show that uninfected snails consumed 40% more
      ephemeral macroalgal biomass than infected snails in the laboratory, probably
      because the digestive system of infected snails is compromised by C. lingua
      infection. In the field, this weaker grazing by infected snails resulted in
      significantly greater expansion of ephemeral macroalgal cover relative to grazing
      by uninfected snails. By decreasing the per-capita grazing rate of the dominant
      herbivore, C. lingua indirectly affects the composition of the macroalgal
      community and may in turn affect other species that depend on macroalgae for
      resources or habitat structure. In light of the abundance of parasites across
      systems, we suggest that, through trait-mediated indirect effects, parasites may
      be a common determinant of structure in ecological communities.

PMID- 17517668
TI  - Holocene morphogenesis of Alexander the Great's isthmus at Tyre in Lebanon.
AB  - In 332 B.C., Alexander the Great constructed an approximately 1,000-m-long
      causeway to seize the offshore island of Tyre. The logistics behind this
      engineering feat have long troubled archaeologists. Using the Holocene
      sedimentary record, we demonstrate that Alexander's engineers cleverly exploited
      a shallow proto-tombolo, or sublittoral sand spit, to breach the offshore city's
      defensive impregnability. We elucidate a three-phase geomorphological model for
      the spit's evolution. Settled since the Bronze Age, the area's geological record
      manifests a long history of natural and anthropogenic forcings. (i) Leeward of
      the island breakwater, the maximum flooding surface (e.g., drowning of the
      subaerial land surfaces by seawater) is dated approximately 8000 B.P. Fine
      grained sediments and brackish and marine-lagoonal faunas translate shallow, low
      energy water bodies at this time. Shelter was afforded by Tyre's elongated
      sandstone reefs, which acted as a 6-km natural breakwater. (ii) By 6000 B.P., sea
      level rise had reduced the dimensions of the island from 6 to 4 km. The leeward
      wave shadow generated by this island, allied with high sediment supply after 3000
      B.P., culminated in a natural wave-dominated proto-tombolo within 1-2 m of mean
      sea level by the time of Alexander the Great (4th century B.C.). (iii) After 332
      B.C., construction of Alexander's causeway entrained a complete anthropogenic
      metamorphosis of the Tyrian coastal system.

PMID- 17517669
TI  - Stochastic fluctuations in metabolic pathways.
AB  - Fluctuations in the abundance of molecules in the living cell may affect its
      growth and well being. For regulatory molecules (e.g., signaling proteins or
      transcription factors), fluctuations in their expression can affect the levels of
      downstream targets in a network. Here, we develop an analytic framework to
      investigate the phenomenon of noise correlation in molecular networks.
      Specifically, we focus on the metabolic network, which is highly interlinked, and
      noise properties may constrain its structure and function. Motivated by the
      analogy between the dynamics of a linear metabolic pathway and that of the
      exactly soluble linear queuing network or, alternatively, a mass transfer system,
      we derive a plethora of results concerning fluctuations in the abundance of
      intermediate metabolites in various common motifs of the metabolic network. For
      all but one case examined, we find the steady-state fluctuation in different
      nodes of the pathways to be effectively uncorrelated. Consequently, fluctuations
      in enzyme levels only affect local properties and do not propagate elsewhere into
      metabolic networks, and intermediate metabolites can be freely shared by
      different reactions. Our approach may be applicable to study metabolic networks
      with more complex topologies or protein signaling networks that are governed by
      similar biochemical reactions. Possible implications for bioinformatic analysis
      of metabolomic data are discussed.

PMID- 17517670
TI  - W values of protons in liquid water.
AB  - The W values of protons in liquid water were calculated for energies from 0.1 keV
      to 10 MeV using the continuous slowing down approximation as well as three models
      for the calculation of the differential ionisation cross-sections of water for
      protons published in recent years. The W values determined by means of the three
      models differ only marginally from each other and lie between 25 and 26 eV at
      proton energies >5 MeV. This high-energy W value is approximately 3 eV lower than
      that in water vapour.

PMID- 17517671
TI  - Installation and application of an intense 7Li(p,n) neutron source for 20-90 MeV
      region.
AB  - An intense (7)Li(p,n) neutron source was installed with the K = 110-MeV
      azimuthally varying field (AVF) cyclotron at the Cyclotron and Radioisotope
      Center (CYRIC), Tohoku University, by employing a special arrangement to allow a
      short target-sample distance down to 1 m. The source can deliver a neutron flux
      around 1.5 x 10(6) n cm(-2) s(-1) with a lithium target of thickness equivalent
      to 2-MeV energy loss and 3-microA proton beam, which is the highest intensity in
      the world. The source is successfully used for (1) measurement of neutron cross
      sections relevant to radiation safety and radiation effect and (2) semiconductor
      irradiation test for single-event effect and (3) characterisation of neutron
      detectors and dosemeters.

PMID- 17517672
TI  - Application of low-cost Gallium Arsenide light-emitting-diodes as kerma dosemeter
      and fluence monitor for high-energy neutrons.
AB  - Displacement damage (DD) caused by fast neutrons in unbiased Gallium Arsenide
      (GaAs) light emitting diodes (LED) resulted in a reduction of the light output.
      On the other hand, a similar type of LED irradiated with gamma rays from a (60)Co
      source up to a dose level in excess of 1.0 kGy (1.0 x 10(5) rad) was found to
      show no significant drop of the light emission. This phenomenon was used to
      develop a low cost passive fluence monitor and kinetic energy released per unit
      mass dosemeter for accelerator-produced neutrons. These LED-dosemeters were used
      to assess the integrated fluence of photoneutrons, which were contaminated with a
      strong bremsstrahlung gamma-background generated by the 730 MeV superconducting
      electron linac driving the free electron laser in Hamburg (FLASH) at Deutsches
      Elektronen-Synchrotron. The applications of GaAs LED as a routine neutron fluence
      monitor and DD precursor for the electronic components located in high-energy
      accelerator environment are highlighted.

PMID- 17517673
TI  - Alanine blends for ESR measurements of thermal neutron fluence in a mixed
      radiation field.
AB  - In this paper, the results of a study on the electron spin resonance (ESR)
      dosimetry to measure thermal neutron fluence in a mixed radiation field (neutron
      and photons) are presented. The ESR responses of alanine dosemeters with
      different additives are compared. In particular, the (10)B-acid boric and the Gd
      oxide were chosen to enhance the sensitivity of alanine dosemeters to thermal
      neutrons. Irradiations were carried out inside the thermal column of the TAPIRO
      reactor of the ENEA center, Casaccia Rome. The main results are a greater neutron
      sensitivity and a smaller lowest detectable fluence for the dosemeters with
      gadolinium than for dosemeters of alanine with (10)B, which is well known to be
      much more sensitive to thermal neutrons than simple alanine.

PMID- 17517674
TI  - Fast response neutron emission monitor for fusion reactor using stilbene
      scintillator and Flash-ADC.
AB  - The stilbene neutron detector which has been used for neutron emission profile
      monitoring in JT-60U has been improved, to respond to the requirement to observe
      the high-frequency phenomena in megahertz region such as toroidicity-induced
      Alfven Eigen mode in burning plasma as well as the spatial profile and the energy
      spectrum. This high-frequency phenomenon is of great interest and one of the key
      issues in plasma physics in recent years. To achieve a fast response in the
      stilbene detector, a Flash-ADC is applied and the wave form of the anode signal
      stored directly, and neutron/gamma discrimination was carried out via software
      with a new scheme for data acquisition mode to extend the count rate limit to MHz
      region from 1.3 x 10(5) neutron/s in the past, and confirmed the adequacy of the
      method.

PMID- 17517675
TI  - Altitude-dependent dose conversion coefficients in EPCARD.
AB  - Conversion coefficients that depend on altitude, cutoff rigidity and solar
      activity were developed and introduced in the European Program Package for the
      Calculation of Aviation Route Doses (EPCARD). A set of specially chosen long
      distance flights were used to compare the new particle effective doses and
      ambient dose equivalents with those calculated using the previous averaged
      constant conversion coefficients. The data show very good agreement to each
      other. The dose differences for the chosen flights are <11%, for typical civil
      flight levels.

PMID- 17517676
TI  - Measurements and simulations of the radiation exposure to aircraft crew
      workplaces due to cosmic radiation in the atmosphere.
AB  - As required by the European Directive 96/29/Euratom, radiation exposure due to
      natural ionizing radiation has to be taken into account at workplaces if the
      effective dose could become more than 1 mSv per year. An example of workers
      concerned by this directive is aircraft crew due to cosmic radiation exposure in
      the atmosphere. Extensive measurement campaigns on board aircrafts have been
      carried out to assess ambient dose equivalent. A consortium of European dosimetry
      institutes within EURADOS WG5 summarized experimental data and results of
      calculations, together with detailed descriptions of the methods for measurements
      and calculations. The radiation protection quantity of interest is the effective
      dose, E (ISO). The comparison of results by measurements and calculations is done
      in terms of the operational quantity ambient dose equivalent, H(10). This paper
      gives an overview of the EURADOS Aircraft Crew In-Flight Database and it presents
      a new empirical model describing fitting functions for this data. Furthermore, it
      describes numerical simulations performed with the Monte Carlo code FLUKA-2005
      using an updated version of the cosmic radiation primary spectra. The ratio
      between ambient dose equivalent and effective dose at commercial flight
      altitudes, calculated with FLUKA-2005, is discussed. Finally, it presents the
      aviation dosimetry model AVIDOS based on FLUKA-2005 simulations for routine dose
      assessment. The code has been developed by Austrian Research Centers (ARC) for
      the public usage (http://avidos.healthphysics.at).

PMID- 17517677
TI  - Advanced multistage deconvolution applied to composite glow peak 5 in LiF:Mg,Ti
      (TLD-100).
AB  - The effects of 'slow-cooling' on the structure of composite peak 5 following low
      ionisation density beta/gamma irradiation are described and analysed in both
      'slow-cooled' and 'normally-cooled' samples. Computerised glow curve
      deconvolution is employed with constrained 'peak-shape' parameters deduced from
      anciliary studies using 4 eV and 5 eV optical excitation.

PMID- 17517678
TI  - Embryonic and postnatal development of the layer I-directed ("matrix")
      thalamocortical system in the rat.
AB  - Inputs to the layer I apical dendritic tufts of pyramidal cells are crucial in
      "top-down" interactions in the cerebral cortex. A large population of
      thalamocortical cells, the "matrix" (M-type) cells, provides a direct robust
      input to layer I that is anatomically and functionally different from the
      thalamocortical input to layer VI. The developmental timecourse of M-type axons
      is examined here in rats aged E (embryonic day) 16 to P (postnatal day) 30.
      Anterograde techniques were used to label axons arising from 2 thalamic nuclei
      mainly made up of M-type cells, the Posterior and the Ventromedial. The primary
      growth cones of M-type axons rapidly reached the subplate of dorsally situated
      cortical areas. After this, interstitial branches would sprout from these axons
      under more lateral cortical regions to invade the overlying cortical plate
      forming secondary arbors. Moreover, retrograde labeling of M-type cell somata in
      the thalamus after tracer deposits confined to layer I revealed that large
      numbers of axons from multiple thalamic nuclei had already converged in a given
      spot of layer I by P3. Because of early ingrowth in such large numbers,
      interactions of M-type axons may significantly influence the early development of
      cortical circuits.

PMID- 17517679
TI  - Quantitative chemical composition of cortical GABAergic neurons revealed in
      transgenic venus-expressing rats.
AB  - Although neocortical GABAergic (gamma-aminobutyric acidergic) interneurons have
      been the focus of intense study, especially in the rat, a consensus view of the
      functional diversity and organization of inhibitory cortical neurons has not yet
      been achieved. To better analyze GABAergic neurons in the rat, we used a
      bacterial artificial chromosome (BAC) construct and established 2 lines of
      transgenic rats that coexpress Venus, a yellow fluorescent protein, with the
      vesicular GABA transporter. The brain GABA content from both transgenic lines was
      similar to the level found in wild-type rats. In the frontal cortex, Venus was
      expressed in >95% of GABAergic neurons, most of which also expressed at least one
      of 6 biochemical markers, including alpha-actitin-2, which preferentially labeled
      late-spiking neurogliaform cells. Taking advantage of the fact that Venus
      expression allows for targeted recording from all classes of nonpyramidal cells,
      irrespective of their somatic morphologies, we demonstrated that fast-spiking
      neurons, which were heterogeneous in somatic size as well as vertical dendritic
      projection, had relatively uniform horizontal dimensions, suggesting a cell type
      specific columnar input territory. Our data demonstrate the benefits of VGAT
      Venus rats for investigating GABAergic circuits, as well as the feasibility of
      using BAC technology in rats to label subsets of specific, genetically defined
      neurons.

PMID- 17517680
TI  - fMRI investigation of working memory for faces in autism: visual coding and
      underconnectivity with frontal areas.
AB  - Brain activation and functional connectivity were investigated in high
      functioning autism using functional magnetic resonance imaging in an n-back
      working memory task involving photographic face stimuli. The autism group showed
      reliably lower activation compared with controls in the inferior left prefrontal
      area (involved in verbal processing and working memory maintenance) and the right
      posterior temporal area (associated with theory of mind processing). The
      participants with autism also showed activation in a somewhat different location
      in the fusiform area than the control participants. These results suggest that
      the neural circuitry of the brain for face processing in autism may be analyzing
      the features of the face more as objects and less in terms of their human
      significance. The functional connectivity results revealed that the abnormal
      fusiform activation was embedded in a larger context of smaller and less
      synchronized networks, particularly indicating lower functional connectivity with
      frontal areas. In contrast to the underconnectivity with frontal areas, the
      autism group showed no underconnectivity among posterior cortical regions. These
      results extend previous findings of abnormal face perception in autism by
      demonstrating that the abnormalities are embedded in an abnormal cortical network
      that manages to perform the working memory task proficiently, using a visually
      oriented, asocial processing style that minimizes reliance on prefrontal areas.

PMID- 17517681
TI  - Vision without proprioception modulates cortico-spinal excitability during hand
      motor imagery.
AB  - Several studies have shown a cortico-spinal facilitation during motor imagery.
      This facilitation effect is weaker when the actual hand posture is incompatible
      with the imagined movement. To determine whether the source of this interference
      effect arises from online proprioceptive information, we examined transcranial
      magnetic stimulation (TMS)-induced motor-evoked potentials during motor imagery
      in the deafferented subject G.L. The patient and 7 control subjects were asked to
      close their eyes and imagine joining the tips of the thumb and the little finger
      while maintaining a hand posture compatible or incompatible with the imagined
      movement. Contrary to control subjects' performance, G.L.'s results show that the
      facilitation observed during motor imagery was independent of the hand posture.
      To examine how vision of the hand interacts with the imagery process, G.L. and
      control subjects performed the same task with the eyes open. Like control
      subjects, when G.L. looked at her hand, a greater facilitation was observed when
      her hand posture was compatible with the imagined movement than when it was
      incompatible. These results suggest that in the absence of proprioception, vision
      may facilitate or inhibit motor representations and support the idea that limb
      position in the brain is organized around multisensory representations.

PMID- 17517682
TI  - Stop-signal reaction-time task performance: role of prefrontal cortex and
      subthalamic nucleus.
AB  - The stop-signal reaction-time (SSRT) task measures inhibition of a response that
      has already been initiated, that is, the ability to stop. Human subjects
      classified as "impulsive," for example, those with attention deficit and
      hyperactivity disorder, are slower to respond to the stop signal. Although
      functional and structural imaging studies in humans have implicated frontal and
      basal ganglia circuitry in the mediation of this form of response control, the
      precise roles of the cortex and basal ganglia in SSRT performance are far from
      understood. We describe effects of excitotoxic fiber-sparing lesions of the
      orbitofrontal cortex (OF), infralimbic cortex (IL), and subthalamic nucleus (STN)
      in rats performing a SSRT task. Lesions to the OF slowed SSRT, whereas lesions to
      the IL or the STN had no effect. On the go-signal trials, neither cortical lesion
      affected go-trial reaction time (GoRT), but STN lesions speeded such latencies.
      The STN lesion also significantly reduced accuracy of stopping at all stop-signal
      delays, indicative of a generalized stopping impairment that was independent of
      the SSRT itself.

PMID- 17517683
TI  - Activity-dependent PSD formation and stabilization of newly formed spines in
      hippocampal slice cultures.
AB  - Development and remodeling of synaptic networks occurs through a continuous
      turnover of dendritic spines. However, the mechanisms that regulate the formation
      and stabilization of newly formed spines remain poorly understood. Here, we
      applied repetitive confocal imaging to hippocampal slice cultures to address
      these issues. We find that, although the turnover rate of protrusions
      progressively decreased during development, the process of stabilization of new
      spines remained comparable both in terms of time course and low level of
      efficacy. Irrespective of the developmental stage, most new protrusions were
      quickly eliminated, in particular filopodia, which only occasionally lead to the
      formation of stable dendritic spines. We also found that the stabilization of new
      protrusions was determined within a critical period of 24 h and that this
      coincided with an enlargement of the spine head and the expression of tagged PSD
      95. Blockade of postsynaptic AMPA and NMDA receptors significantly reduced the
      capacity of new spines to express tagged PSD-95 and decreased their probability
      to be stabilized. These results suggest a model in which synaptic development is
      associated with an extensive, nonspecific growth of protrusions followed by
      stabilization of a few of them through a mechanism that involves activity-driven
      formation of a postsynaptic density.

PMID- 17517684
TI  - Pneumococcal carriage in United Kingdom families: estimating serotype-specific
      transmission parameters from longitudinal data.
AB  - Repeated observations of pneumococcal infection in 121 United Kingdom families
      (October 2001-July 2002) were used to explore the transmission properties of five
      highly prevalent pneumococcal serotypes (6A, 6B, 14, 19F, 23F). A family-based
      Markov model was developed, and maximum likelihood estimates were produced for
      model parameters. The authors found higher community acquisition rates among
      preschool children for all serotypes and higher within-household transmission for
      6A and 14. Significant differences in the spontaneous clearance rate were
      estimated between age categories and serotypes, with 6B being carried for almost
      4 months in children. Different mechanisms of competition between serotypes were
      investigated, and a complete exclusion model (i.e., the resident strain cannot be
      outcompeted by challengers) was discarded in favor of a competing mechanism that
      leaves a resident serotype partially or fully susceptible to challengers. Large
      variation was found in the challenging strength, which was low for 19F and 23F
      and high for 6A and 6B. Serotype 6B was the only one characterized by high
      resistance capacity. Only small differences in the transmission characteristics
      were found when vaccine and nonvaccine serotypes were grouped, suggesting that a
      serotype-specific analysis is needed to detect distinctive serotype behavior.

PMID- 17517685
TI  - Abstracts of the 40th Annual Meeting of the Society for Epidemiologic Research,
      June 19-22, 2007, Boston , Massachusetts, USA.

PMID- 17517686
TI  - Rai1 deficiency in mice causes learning impairment and motor dysfunction, whereas
      Rai1 heterozygous mice display minimal behavioral phenotypes.
AB  - Smith-Magenis syndrome (SMS) is associated with an approximately 3.7 Mb common
      deletion in 17p11.2 and characterized by its craniofacial and neurobehavioral
      abnormalities. The reciprocal duplication leads to dup(17)(p11.2p11.2) associated
      with the Potocki-Lupski syndrome (PLS), a neurological disorder whose features
      include autism. Retinoic acid induced 1 (RAI1) appears to be responsible for the
      majority of clinical features in both SMS and PLS. Mouse models of these
      syndromes harboring an approximately 2 Mb chromosome engineered deletion and
      duplication, respectively, displayed abnormal locomotor activity and/or learning
      deficits. To determine the contribution of RAI1 in the neurobehavioral traits in
      SMS, we performed a battery of behavioral tests on Rai1 mutant mice and the
      Df(11)17-1/+ mice that have a small deletion of approximately 590 kb. The mice
      with the small deletion were hypoactive like the large deletion mice and they
      also showed learning deficits. The Rai1+/- mice exhibited normal locomotor
      activity. However, they had an abnormal electroencephalogram with overt seizure
      observed in a subset of mice. The few surviving Rai1-/- mice displayed more
      severe neurobehavioral abnormalities including hind limb clasping, overt
      seizures, motor impairment and context- and tone-dependant learning deficits. X
      gal staining of the Rai1+/- mice suggests that Rai1 is predominantly expressed in
      neurons of the hippocampus and the cerebellum. Our results suggest that Rai1 is a
      critical gene in the central nervous system functioning in a dosage sensitive
      manner and that the neurobehavioral phenotype is modified by regulator(s) in the
      approximately 590 kb genomic interval, wherein the major modifier affecting the
      craniofacial penetrance resides.

PMID- 17517687
TI  - Association of variants in the BAT1-NFKBIL1-LTA genomic region with protection
      against myocardial infarction in Europeans.
AB  - Single-nucleotide polymorphisms within the BAT1-NFKBIL1-LTA genomic region
      (6p21.3) and the LGALS2 gene (22q13.1), encoding a regulator for lymphotoxin
      alpha, the product of the LTA gene, have been reported to be linked with the risk
      of myocardial infarction in Japanese. We employed nine polymorphisms from the
      BAT1-NFKBIL1-LTA region and one polymorphism from the LGALS2 gene, and
      investigated whether such associations were also present in Europeans. The study
      included 3657 patients with myocardial infarction and 1211 control individuals
      with angiographically normal coronary arteries. Minor homozygous genotypes of
      polymorphisms in BAT1 (rs2239527, -23C/G), NFKBIL1 (rs2071592, -63T/A) and LTA
      (rs1800683, -162G/A; rs909253, 252G/A; rs1041981, Thr26Asn) were associated with
      moderately protective effects against myocardial infarction (P </= 0.045). The
      most abundant 9-marker haplotype of the BAT1-NFKBIL1-LTA region, named haplotype
      1 (28% frequency in the study population), included the alleles of the five
      protective genotypes and was related with a significantly lower risk of
      myocardial infarction (OR 0.88, 95% CI 0.80-0.98; P = 0.015). Moreover,
      homozygosity for haplotype 1 was associated with an OR 0.72 (95% CI 0.57-0.90; P
      = 0.0047). Multiple logistic regression analysis revealed an independent
      protective effect against myocardial infarction in the homozygous carriers of
      haplotype 1 (adjusted OR 0.78, 95% CI 0.62-0.99; P = 0.043). A putative risk
      genotype of the polymorphism in the LGALS2 gene (rs7291467; 3279T/C) was not
      associated with myocardial infarction (OR 0.98, 95% CI 0.83-1.16; P = 0.84). Our
      finding that protective effects are linked with minor homozygous genotypes and
      haplotype 1 of the BAT1-NFKBIL1-LTA region in Europeans is opposite to the
      observation of associated risks in Japanese.

PMID- 17517688
TI  - Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers:
      case control study.
AB  - CHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can
      cause arrest or apoptosis in response to unrepaired DNA damage. We report a large
      case-control study of a non-functional variant that had previously been expected
      to increase cancer rates. Four thousand and fifteen cancer patients (2250 lung,
      811 squamous upper aero-digestive and 954 kidney) and 3052 controls in central
      Europe were genotyped for the mis-sense variant rs17879961 (replacement of T by
      C), which changes an amino acid (I157T) in an active site of the gene product.
      The heterozygous (T/C) genotype was associated with a highly significantly lower
      incidence of lung cancer than the common T/T genotype [relative risk (RR), T/C
      versus T/T, 0.44, with 95% confidence interval (CI) 0.31-0.63, P < 0.00001] and
      with a significantly lower incidence of upper aero-digestive cancer (RR 0.44, CI
      0.26-0.73, P = 0.001; P = 0.000001 for lung or upper aero-digestive cancer).
      Protection was significantly greater for squamous than adenomatous lung cancer (P
      = 0.001). There was an increase of borderline significance in kidney cancer (RR
      1.44, CI 0.99-2.00, P = 0.06). This unexpected halving of tobacco-related cancer
      (since replicated independently) implies much greater absolute risk reduction in
      smokers than in non-smokers. The mechanism is unknown: perhaps squamous stem cell
      apoptosis following smoke exposure causes net harm (e.g. by forcing nearby stem
      cells to divide before they have repaired their own DNA damage from tobacco
      smoke). If so, reducing the rate of apoptosis by reducing CHEK2 activity could be
      protective-although not smoking would be far more so.

PMID- 17517689
TI  - Missense mutations associated with Diamond-Blackfan anemia affect the assembly of
      ribosomal protein S19 into the ribosome.
AB  - RPS19 has been identified as the first gene associated with Diamond-Blackfan
      anemia (DBA), a rare congenital hypoplastic anemia that includes variable
      physical malformations. It is mutated in approximately 25% of the patients
      although doubts remain as to whether DBA clinical phenotype depends on the
      ribosomal function of RPS19 or on an extra-ribosomal role or on both. RPS19 mRNAs
      with mutations that introduce premature stop codons or eliminate it are rapidly
      turned over by the surveillance mechanisms possibly causing a decrease in the
      RPS19 protein level. A decrease in RPS19 level has been shown to cause a defect
      in the maturation of 18S ribosomal RNA. Less clear is the effect of missense
      mutations in RPS19. With the aim of analyzing the functional features of mutated
      RPS19, we prepared cDNA constructs expressing RPS19 containing 11 missense
      mutations and a trinucleotide insertion found in DBA patients. After
      transfection, we analyzed the following properties of the mutated proteins: (i)
      protein stability, (ii) subcellular localization and (iii) assembly into
      ribosomes. Our results indicate that some RPS19 mutations alter the capacity of
      the protein to localize in nucleolar structure and these mutated RPS19 are very
      unstable. Moreover, none of the mutated RPS19 analyzed in this study, including
      those proteins that appear localized into the nucleolus, is able to be assembled
      into mature ribosome.

PMID- 17517690
TI  - A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing
      efficiency and associates with increased cholesterol.
AB  - Single nucleotide polymorphisms (SNPs) that alter exon splicing efficiency are an
      emerging class of functional genetic variants. Since mutations in low-density
      lipoprotein receptor (LDLR) are a primary cause of familial hypercholesterolemia,
      we evaluated whether LDLR SNPs may alter splicing efficiency and cholesterol
      homeostasis. A SNP within LDLR exon 12, rs688, was identified in silico as
      neutralizing a putative exon splicing enhancer. Studies in human liver samples
      established that this SNP was associated with significantly decreased LDLR exon
      12 splicing efficiency in women in vivo. In vitro minigene splicing studies
      qualitatively replicated these in vivo results and demonstrated that rs688
      specifically modulates splicing efficiency. These effects on splicing may be
      physiologically relevant because the presence of the rs688 minor allele
      associates with increased total and LDL-cholesterol in female members of the
      Framingham Offspring Study. The largest rs688-associated cholesterol differences
      were observed in pre-menopausal women. In summary, these studies identify an LDLR
      SNP present in approximately 60% of Caucasians that is associated with
      significant 10% increases in total and LDL-cholesterol in pre-menopausal women.

PMID- 17517691
TI  - Impairments in impulse control in mice transgenic for the human FTDP-17 tauV337M
      mutation are exacerbated by age.
AB  - Abnormalities in microtubule-associated tau protein are a key neuropathological
      feature of both Alzheimer's disease and many frontotemporal dementias (FTDs),
      including hereditary FTD with Parkinsonism linked to chromosome 17 (FTDP-17). In
      these disorders, tau becomes aberrantly phosphorylated, leading to the
      development of filamentous neurofibrillary tangles in the brain. Here we report,
      in a longitudinal ageing study, the sensorimotor and cognitive assessment of
      transgenic mice expressing the human tau(V337M) ('Seattle Family A') FTDP-17
      mutation, which we have previously shown to demonstrate abnormalities in brain
      tau phosphorylation. The data indicated highly specific effects of transgene
      expression on the ability to withhold responding in a murine version of the 5
      choice serial reaction time task, behaviour consistent with deficits in impulse
      control. Ageing exacerbated these effects. In young tau(V337M) mice, increased
      impulsivity was present under task conditions making inhibition of premature
      responding more difficult (longer inter-trial intervals) but not under baseline
      conditions. However, when older, the tau(V337M) mice showed further increases in
      premature responding, including under baseline conditions. These impulse control
      deficits were fully dissociable from sensorimotor or motivation effects on
      performance. The findings recapitulate core abnormalities in impulsive responding
      observed in both frontal variant FTD and FTDP-17 linked to the tau(V337M)
      mutation in humans.

PMID- 17517692
TI  - Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for
      vertebrate laterality determination.
AB  - Oculofaciocardiodental (OFCD) syndrome is an X-linked male lethal condition
      encompassing cardiac septal defects, as well as ocular and dental anomalies. The
      gene mutated in OFCD syndrome, the BCL-6 corepressor (BCOR), is part of a
      transcriptional repression complex whose transcriptional targets remain largely
      unknown. We reviewed cases of OFCD syndrome and identified patients exhibiting
      defective lateralization including dextrocardia, asplenia and intestinal
      malrotation, suggesting that BCOR is required in normal laterality determination.
      To study the function of BCOR, we used morpholino oligonucleotides (MOs) to
      knockdown expression of xtBcor in Xenopus tropicalis, thus creating an animal
      model for OFCD syndrome. The resulting tadpoles had cardiac and ocular features
      characteristic of OFCD syndrome. Reversed cardiac orientation and disorganized
      gut patterning were seen when MOs were injected into the left side of embryos,
      demonstrating a left-sided requirement for xtBcor in lateral determination in
      Xenopus. Ocular defects displayed no left-right bias and included anterior and
      posterior segment disorders such as microphthalmia and coloboma. Expression of
      xtPitx2c was shown to be downregulated when xtBcor was depleted. This identifies
      a pathway in which xtBcor is required for lateral specification, a process
      intrinsically linked to correct cardiac septal development.

PMID- 17517693
TI  - Mutations in splicing factor PRPF3, causing retinal degeneration, form
      detrimental aggregates in photoreceptor cells.
AB  - PRPF3 is an element of the splicing machinery ubiquitously expressed, yet
      mutations in this gene are associated with a tissue-specific phenotype: autosomal
      dominant retinitis pigmentosa (RP). Here, we studied the subcellular localization
      of endogenous- and mutant-transfected PRPF3. We found that (i) subcellular
      distribution of the endogenous wild-type protein co-localizes with small nuclear
      ribonucleoproteins, partially with a nucleolar marker and accumulates in speckles
      labeled by SC35; (ii) in human retinas, PRPF3 does not show a distinctive
      abundance in photoreceptors, the cells affected in RP and (iii) the RP causing
      mutant PRPF3, differently from the wild-type protein, forms abnormally big
      aggregates in transfected photoreceptor cells. Aggregation of T494M mutant PRPF3
      inside the nucleus triggers apoptosis only in photoreceptor cells. On the basis
      of the observation that mutant PRPF3 accumulates in the nucleolus and that
      transcriptional, translational and proteasome inhibition can induce this
      phenomenon in non-photoreceptor cells, we hypothesize that mutation affects
      splicing factor recycling. Noteworthy, accumulation of the mutant protein in big
      aggregates also affects distribution of some other splicing factors. Our data
      suggest that the mutant protein has a cell-specific dominant effect in rod
      photoreceptors while appears not to be harmful to epithelial and fibroblast
      cells.

PMID- 17517695
TI  - The testis anion transporter 1 (Slc26a8) is required for sperm terminal
      differentiation and male fertility in the mouse.
AB  - The Slc26 family is a conserved family of anion transporters. In the human, their
      physiological relevance was highlighted with the discovery of pathogenic
      mutations in several Slc26 transporters that lead to distinctive clinical
      disorders (Pendred syndrome, deafness, diastrophic dysplasia, congenital chloride
      diarrhoea) that are related to the specific distribution of these genes. We
      previously identified TAT1 as a new family member (Slc26A8), very specifically
      expressed in male germ cells in both the human and the mouse. To investigate Tat1
      function in the male germline, we generated mice with a targeted disruption of
      the Tat1 gene. Heterozygous and homozygous Tat1 mutant mice were
      indistinguishable from wild-type littermates concerning survival rate, general
      appearance and gross behaviour; however, Tat1 null males were sterile due to
      complete lack of sperm motility and reduced sperm fertilization potential. Ultra
      structural analysis revealed defects in flagellar differentiation leading to an
      abnormal annulus, disorganization of the midpiece-principal piece junction,
      hairpin bending of the sperm tail with disruption of the axial structures, and
      abnormal mitochondrial sheath assembly. While ATP levels were normal, ATP
      consumption was strongly reduced in Tat1 null spermatozoa. Interestingly, Tat1 is
      located at the annulus, a septin-based circular structure connecting the midpiece
      to the principal piece. Altogether, our results indicate that Tat1 is a critical
      component of the sperm annulus that is essential for proper sperm tail
      differentiation and motility.

PMID- 17517694
TI  - Decreased chondrocyte proliferation and dysregulated apoptosis in the cartilage
      growth plate are key features of a murine model of epiphyseal dysplasia caused by
      a matn3 mutation.
AB  - Disruption to endochondral ossification leads to delayed and irregular bone
      formation and can result in a heterogeneous group of genetic disorders known as
      the chondrodysplasias. One such disorder, multiple epiphyseal dysplasia (MED), is
      characterized by mild dwarfism and early-onset osteoarthritis and can result from
      mutations in the gene encoding matrilin-3 (MATN3). To determine the disease
      mechanisms that underpin the pathophysiology of MED we generated a murine model
      of epiphyseal dysplasia by knocking-in a matn3 mutation. Mice that are homozygous
      for the mutation develop a progressive dysplasia and have short-limbed dwarfism
      that is consistent in severity with the relevant human phenotype. Mutant matrilin
      3 is retained within the rough endoplasmic reticulum of chondrocytes and is
      associated with an unfolded protein response. Eventually, there is reduced
      proliferation and spatially dysregulated apoptosis of chondrocytes in the
      cartilage growth plate, which is likely to be the cause of disrupted linear bone
      growth and the resulting short-limbed dwarfism in the mutant mice.

PMID- 17517696
TI  - Meta-analysis of association between the ASPN D-repeat and osteoarthritis.
AB  - Osteoarthritis (OA) is the most common form of human arthritis. Genetic factors
      have been implicated in OA. It was reported that an aspartic acid (D)-repeat
      polymorphism in the gene encoding asporin (ASPN) was associated with OA of knee
      and hip joints in Japanese; in the three independent studies performed, the D14
      allele of the ASPN polymorphism was over-represented and the D13 allele was under
      represented. Subsequently, four replication studies, three in Europeans and one
      in Chinese populations, have been reported; however, they showed inconsistent
      results. To evaluate between-study heterogeneity and to estimate the common
      genetic effect of the D-repeat polymorphism on OA, we performed a meta-analysis
      of the five reports that include seven association studies, using the DerSimonian
      Laird procedure. We detected association between knee OA and the susceptible D14
      allele [P = 0.003, summary odds ratio (OR) = 1.46] with significant heterogeneity
      (P = 0.047) among the studies. We also detected positive association between knee
      OA and the protective D13 allele (P = 0.026, summary OR = 0.84) with significant
      heterogeneity (P = 0.040) among the studies. Because of significant
      heterogeneity, we stratified the studies by ethnicity. We detected positive
      association between knee OA and the D14 allele (P = 0.0000013, summary OR = 1.95)
      with non-significant heterogeneity (P = 0.535) in Asian populations. In hip OA,
      significant heterogeneity was identified and there was no positive association
      for any allele in any comparison. The present results suggest that the
      association of the ASPN D14 allele and knee OA has global relevance, but that its
      effect has ethnic differences.

PMID- 17517697
TI  - Letter to the editor: Mastitis treatment trials.

PMID- 17517698
TI  - Invited review: Essential oils as modifiers of rumen microbial fermentation.
AB  - Microorganisms in the rumen degrade nutrients to produce volatile fatty acids and
      synthesize microbial protein as an energy and protein supply for the ruminant,
      respectively. However, this fermentation process has energy (losses of methane)
      and protein (losses of ammonia N) inefficiencies that may limit production
      performance and contribute to the release of pollutants to the environment.
      Antibiotic ionophores have been very successful in reducing these energy and
      protein losses in the rumen, but the use of antibiotics in animal feeds is facing
      reduced social acceptance, and their use has been banned in the European Union
      since January 2006. For this reason, scientists have become interested in
      evaluating other alternatives to control specific microbial populations to
      modulate rumen fermentation. Essential oils can interact with microbial cell
      membranes and inhibit the growth of some gram-positive and gram-negative
      bacteria. As a result of such inhibition, the addition of some plant extracts to
      the rumen results in an inhibition of deamination and methanogenesis, resulting
      in lower ammonia N, methane, and acetate, and in higher propionate and butyrate
      concentrations. Results have indicated that garlic oil, cinnamaldehyde (the main
      active component of cinnamon oil), eugenol (the main active component of the
      clove bud), capsaicin (the active component of hot peppers), and anise oil, among
      others, may increase propionate production, reduce acetate or methane production,
      and modify proteolysis, peptidolysis, or deamination in the rumen. However, the
      effects of some of these essential oils are pH and diet dependent, and their use
      may be beneficial only under specific conditions and production systems. For
      example, capsaicin appears to have small effects in high-forage diets, whereas
      the changes observed in high-concentrate diets (increases in dry matter intake
      and total VFA, and reduction in the acetateto-propionate ratio and ammonia N
      concentration) may be beneficial. Because plant extracts may act at different
      levels in the carbohydrate and protein degradation pathways, their careful
      selection and combination may provide a useful tool to manipulate rumen microbial
      fermentation effectively. However, additional research is required to establish
      the optimal dose in vivo in units of the active component, to consider the
      potential adaptation of microbial populations to their activities, to examine the
      presence of residues in the products (milk or meat), and to demonstrate
      improvements in animal performance.

PMID- 17517699
TI  - Butter composition and texture from cows with different milk fatty acid
      compositions fed fish oil or roasted soybeans.
AB  - Changing the milk fatty acid composition can improve the nutritional and physical
      properties of dairy products and their acceptability to consumers. A more
      healthful milk fatty acid composition can be achieved by altering the cow's diet,
      for example, by feeding supplemental fish oil (FO) or roasted soybeans (RSB), or
      by selecting cows with a more unsaturated milk fatty acid composition. We
      examined whether feeding supplemental FO or RSB to cows that had a more
      unsaturated milk fatty acid composition acted additively to produce butter with
      improved fatty acid composition and texture. Using a 3 x 3 Latin square design
      with 2 replications, we fed diets to multiparous Holstein cows (60 to 200 DIM)
      chosen for producing either more or less unsaturated milk fatty acid composition
      (n = 6 for each group) for three 3-wk periods. The control diet contained 3.7%
      crude fat and the 2 experimental diets contained, on a dry matter basis, 0.8% of
      additional lipids in the form of 0.9% of FO or 5% of RSB. The milk, collected in
      the third week of feeding, was used to make butter, which was analyzed for its
      fatty acid composition and physical properties. Dry matter intake, milk yield,
      and milk composition were not significantly affected by cow diet or by cow
      selection. Cows that produced a more unsaturated and healthful milk fat prior to
      the feeding study, according to a "health-promoting index" [HPI = (sum of % of
      unsaturated fatty acids)/ (%12:0 + 4 x %14:0 + %16:0)], maintained a higher HPI
      in their butter during the feeding study than did cows with a low HPI. Milk from
      cows fed supplemental FO or RSB yielded more unsaturated butters with a higher
      HPI. This butter also was softer when the cows were fed RSB. Feeding RSB to cows
      chosen for their high milk HPI yielded the most unsaturated butter with the
      highest HPI and softest texture. Thus, selecting cows with a more health
      promoting milk fatty acid composition and feeding supplemental RSB can be used in
      combination to produce butter that has a consumer-friendly texture and a
      healthful fatty acid profile.

PMID- 17517700
TI  - Gelation upon long storage of milk drinks with carrageenan.
AB  - The carrageenan-induced stabilization and gelation of ultra-high-temperature
      treated milk was studied during long storage. Severe heating (causing increased
      protein denaturation), lowering of the pH, or the use of kappa-carrageenan
      (instead of iota-carrageenan) led to excessive gelation. It is suggested that the
      balance between carrageenan-carrageenan interactions and carrageenan-protein
      interactions determines the gel strength. If the interactions between carrageenan
      and proteins are decreased, more carrageenan is available for carrageenan
      carrageenan interactions, leading to a stronger gel. This is the case if kappa
      carrageenan is used instead of iota-carrageenan because the former forms weaker
      interactions with proteins than the latter. Also, heating and pH influence the
      attachment of whey proteins to the casein micelle surface, hindering the
      attachment of carrageenan to the casein proteins. Upon storage, gel strength
      increased. Particle size and rheology measurements indicated that upon storage,
      tenuous carrageenan-protein aggregates are formed. The firming of the gel was
      probably related to slow structural arrangements of the gel and not related to
      slowly changing calcium equilibria or age gelation.

PMID- 17517701
TI  - Effect of insoluble calcium concentration on rennet coagulation properties of
      milk.
AB  - Rennet-induced gels were made from milk acidified to various pH values or milk at
      pH 6.0 that had added EDTA. The objective was to examine the effect of removing
      insoluble Ca (INS Ca) from casein micelles (CM) on rennet gelation properties.
      For the pH trial, diluted lactic acid was added to reconstituted skim milk to
      decrease the pH to 6.4, 6.0, 5.8, 5.6, and 5.4. For the EDTA trial, EDTA was
      slowly added (0, 2, 4, and 6 mM) to reconstituted skim milk, and the final pH
      values were subsequently adjusted to pH 6.0. Dynamic low amplitude oscillatory
      rheology was used to monitor gel development. The Ca content of CM and rennet
      wheys made from these milks was measured using inductively coupled plasma
      spectroscopy. The INS Ca content of milk was altered by the acidification pH
      values or level of EDTA added. In all samples, the storage modulus (G' )
      exhibited a maximum (GM), with a decrease in G' during longer aging times. Gels
      made at pH 6.4 had higher GM compared with gels made at pH 6.7 probably due to
      the reduction in electrostatic repulsion, whereas the INS Ca content only
      slightly decreased. The highest GM value of gels was observed at pH 6.4 and the
      GM value decreased with decreasing pH from 6.4 to 5.4. This was due to an
      excessive loss of INS Ca from CM. There was a decrease in GM with the increase in
      the concentration of added EDTA, which was probably due to the loss of colloidal
      calcium phosphate, which weakens the integrity of CM. Loss tangent (LT) values at
      GM increased with a reduction in milk pH and the addition of EDTA to milk. Rennet
      gels at the point of the GM were subjected to constant low shearing to fracture
      the gels. With a reduction in INS Ca content, the yield stress decreased, whereas
      LT values increased indicating a weaker, more flexible casein network.
      Microstructure of rennet-induced gels near the GM point and 2 to 10 h after this
      point was studied using fluorescence microscopy. At GM, gels made from milk
      acidified to pH 6.4 exhibited more branched, interconnected networks, whereas
      strands and clusters became larger with a reduction in milk pH to 5.4. Gels made
      from milk with EDTA added had more finely dispersed protein clusters compared
      with gels made from milk with no EDTA added. These microscopic observations
      supported the effect of loss of INS Ca on GM and LT. There was a decrease in
      apparent interconnectivity between strands in gel microstructure during aging,
      which agreed with the decrease in G' after GM. It can be concluded that low
      levels of solubilization of INS Ca and the decrease in milk pH resulted in an
      increase in GM. With greater losses of INS Ca there was excessive reduction in
      cross-linking within CM, which resulted in weaker, more flexible rennet gels.
      This complex behavior cannot be explained by adhesive hard sphere models for CM
      or rennet gels made from these CM.

PMID- 17517702
TI  - Milk and urine excretion of polycyclic aromatic hydrocarbons and their
      hydroxylated metabolites after a single oral administration in ruminants.
AB  - The aim of this study was to establish the transfer of phenanthrene, pyrene, and
      benzo[a]pyrene and their major hydroxylated metabolites to milk and to urine
      after a single oral administration (100 mg per animal of each compound) in 4
      lactating goats. Detection and identification of the analytes (native compounds,
      1-OH pyrene, 3-OH phenanthrene, 3-OH benzo[a]pyrene) were achieved using gas
      chromatography-mass spectrometry. Benzo[a]pyrene, phenanthrene, and pyrene were
      rapidly detected in the plasma stream, whereas 1-OH pyrene and 3-OH phenanthrene
      appeared later in plasma. These data suggest that pyrene and phenanthrene are
      progressively metabolized within the organism. Recovery rates of pyrene and
      phenanthrene in milk over a 24-h period appeared to be very low (0.014 and
      0.006%, respectively), whereas the transfer rates of their corresponding
      metabolites were significantly higher: 0.44% for 1-OH pyrene and 0.073% for 3-OH
      phenanthrene. Recovery rates in urine were found to be higher (1 to 10 times)
      than recovery rates in milk. The 1-OH pyrene was found to be the main metabolite
      in urine as well as in milk. Thus, as has been established for humans, 1-OH
      pyrene could be considered as a marker of ruminant exposure to polycyclic
      aromatic hydrocarbons. Because 1-OH pyrene and 3-OH phenanthrene were measured in
      milk (unlike their corresponding native molecules), metabolites of polycyclic
      aromatic hydrocarbons should be taken into consideration when evaluating the
      safety of milk. Benzo[a]pyrene and 3-OH benzo[a]pyrene were (less than 0.005%)
      transferred to milk and urine in very slight amounts. This very limited transfer
      rate of both compounds suggests a low risk of exposure by humans to
      benzo[a]pyrene or its major metabolite from milk or milk products.

PMID- 17517703
TI  - Effect of Bifidobacterium bifidum fermented milk on Helicobacter pylori and serum
      pepsinogen levels in humans.
AB  - Helicobacter pylori infection is an important risk factor for gastric diseases.
      Some probiotics are useful for suppressing H. pylori infection. Bifidobacterium
      bifidum YIT 4007 can improve the experimental gastric injury in rats and the
      disease stages on the gastric mucosa in peptic ulcer patients. We evaluated the
      fermented milk using a clone (BF-1) having the stronger ability to survive in the
      product than this parent strain to clarify the in vitro suppressive effect of BF
      1 on H. pylori and the in vivo efficacy of BF-1 fermented milk on H. pylori and
      gastric health. In the mixed culture assay of BF-1 and H. pylori, the number of
      pathogens was decreased such that it was not detected after 48 h in the Brucella
      broth with a decrease in pH values. In the cell culture experiment with human
      gastric cells, the H. pylori infection-induced IL-8 secretion was suppressed by
      the preincubation of BF-1. In a human study of 12-wk ingestion (BF-1 group, n =
      40; placebo group, n = 39) with a randomized double-blind placebo-control design,
      the H. pylori urease activity and gastric situation were evaluated using a urea
      breath test (UBT) and the serum pepsinogen (PG) levels as biomarkers for
      inflammation or atrophy, respectively. In the H. pylori-positive subjects, the
      difference (DeltaUBT) of the UBT value from the baseline value in the BF-1 group
      (n = 34) was lower than that in the placebo group (n = 35) at 8 wk. The baseline
      UBT values showed a negative correlation with DeltaUBT values at 8 and 12 wk in
      the BF-1 group but not in the placebo. In the PG-positive subjects classified by
      the PG test method, the BF-1 group was lower in DeltaUBT values than the placebo
      group at 8 and 12 wk. In the active gastritis class by PG levels, the BF-1 group
      was lower in their DeltaUBT values than the placebo at 8 and 12 wk. The PG I
      levels in the BF-1 group were lower than the placebo at 12 wk. The PG II levels
      in the BF-1 group did not change during the ingestion period, but the placebo was
      increased. The PG I/II ratios slightly decreased from baseline at 12 and 20 wk in
      the BF-1 and placebo groups. These patterns were also observed in the H. pylori
      positive subjects. The improving rates of upper gastrointestinal symptomatic
      subjects and total symptom numbers in the BF-1 group were higher than those in
      the placebo. These results indicate that BF-1 fermented milk may affect H. pylori
      infection or its activity, gastric mucosal situation, and the emergence of upper
      gastrointestinal symptoms.

PMID- 17517704
TI  - Industrial yogurt manufacture: monitoring of fermentation process and improvement
      of final product quality.
AB  - Lactic acid fermentation during the production of skim milk and whole fat set
      style yogurt was continuously monitored by measuring pH. The modified Gompertz
      model was successfully applied to describe the pH decline and viscosity
      development during the fermentation process. The viscosity and incubation time
      data were also fitted to linear models against ln(pH). The investigation of the
      yogurt quality improvement practices included 2 different heat treatments (80
      degrees C for 30 min and 95 degrees C for 10 min), 3 milk protein fortifying
      agents (skim milk powder, whey powder, and milk protein concentrate) added at
      2.0%, and 4 hydrocolloids (kappa-carrageenan, xanthan, guar gum, and pectin)
      added at 0.01% to whole fat and skim yogurts. Heat treatment significantly
      affected viscosity and acetaldehyde development without influencing incubation
      time and acidity. The addition of whey powder shortened the incubation time but
      had a detrimental effect on consistency, firmness, and overall acceptance of
      yogurts. On the other hand, addition of skim milk powder improved the textural
      quality and decreased the vulnerability of yogurts to syneresis. Anionic
      stabilizers (kappa-carrageenan and pectin) had a poor effect on the texture and
      palatability of yogurts. However, neutral gums (xanthan and guar gum) improved
      texture and prevented the wheying-off defect. Skim milk yogurts exhibited longer
      incubation times and higher viscosities, whereas they were rated higher during
      sensory evaluation than whole fat yogurts.

PMID- 17517705
TI  - Effect of iron saturation on the recovery of lactoferrin in rennet whey coming
      from heat-treated skim milk.
AB  - This study aimed to determine the effect of thermal treatments on the recovery of
      lactoferrin in whey coming from rennet-coagulated skim milk. The impact of
      lactoferrin iron saturation was also assessed using skim milk spiked with
      different lactoferrin iron forms. The recovery of lactoferrin in the rennet whey
      fraction was determined by reverse-phase HPLC. One- and 2-dimensional sodium
      dodecyl sulfate PAGE analyses were performed on rennet curds to characterize the
      protein interactions involving lactoferrin in heated milk. The extent of
      lactoferrin recovered in the whey fraction was found to reduce as the heating
      temperature increased. The binding of iron by lactoferrin improved its thermal
      stability and its recovery in the whey fraction. Poly-acrylamide gel
      electrophoresis results showed that the association of lactoferrin in the
      unheated milk rennet curd involved noncovalent interactions, whereas upon
      heating, lactoferrin also interacted via an intermolecular disulfide link.
      Depending on the severity of the heat treatment, lactoferrin aggregates with Cys
      containing proteins (beta-lactoglobulin, alpha-lactalbumin, alpha(s2)-casein, and
      kappa-casein) occurred by intermolecular thiol/disulfide exchange reactions.
      These noncovalent and covalent interactions explained the lower recovery of
      lactoferrin in heated milk.

PMID- 17517706
TI  - Thermocalcic aggregation of milk fat globule membrane fragments from acid
      buttermilk cheese whey.
AB  - Fragments originating from the milk fat globule membrane (MFGM), which is rich in
      polar lipids and membrane-specific proteins, are gaining interest for their
      functional and nutritional properties. Acid buttermilk cheese whey was used as a
      source for MFGM purification, because its MFGM content is more than 5 times
      higher than that of standard rennet whey. Because polar lipids are the main
      constituent of the MFGM and only occur in membranous structures, the polar lipid
      content was taken as a parameter for the total MFGM fragment content. The process
      of thermocalcic aggregation was evaluated on its recovery of MFGM fragments in
      the pellet. This method, originally intended for whey clarification and
      defatting, is a combination of calcium addition, a pH increase, and a thermal
      treatment. The influence of pH (6.5 to 8), temperature (40 to 70 degrees C), and
      calcium concentration (0.1 to 0.24 g/100 g) on the pellet mass and dry matter
      (DM) content and on recovery of protein and polar lipids (and thus indirectly on
      MFGM fragments) was investigated by means of a response surface Box-Behnken
      orthogonal design. Reduced quadratic models were fit to the experimental data and
      were found to be highly significant. No outliers were observed. The recovery of
      MFGM fragments was found to be highly dependent on the pH, and less dependent on
      temperature and calcium addition. Next to MFGM proteins, whey proteins were also
      found to be involved in the formation of aggregates. Optimal conditions were
      found at 55 degrees C, pH 7.7, and 0.205 g of calcium/L of whey. Under these
      conditions, 91.0% of the whey polar lipids were recovered in a firm and compact
      pellet of only 7.86% of the original whey mass, with a polar lipid concentration
      of 8.34% on pellet DM. Washing with water and centrifugation of the pellet was
      successful because after one washing step, virtually all sugars were removed,
      whereas 75.9% of the whey polar lipids could still be recovered. As such, the
      polar lipid content of the washed pellet increased to 10.70% on a DM basis.
      However, a second washing step resulted in serious losses of MFGM material.

PMID- 17517707
TI  - Effect of type of concentrated sweet cream buttermilk on the manufacture, yield,
      and functionality of pizza cheese.
AB  - Sweet cream buttermilk (SCB) is a rich source of phospholipids (PL). Most SCB is
      sold in a concentrated form. This study was conducted to determine if different
      concentration processes could affect the behavior of SCB as an ingredient in
      cheese. Sweet cream buttermilk was concentrated by 3 methods: cold ( < 7 degrees
      C) UF, cold reverse osmosis (RO), and evaporation (EVAP). A washed, stirred-curd
      pizza cheese was manufactured using the 3 different types of concentrated SCB as
      an ingredient in standardized milk. Cheesemilks of casein:fat ratio of 1.0 and
      final casein content approximately 2.7% were obtained by blending ultrafiltered
      (UF)-SCB retentate (19.9% solids), RO-SCB retentate (21.9% solids), or EVAP-SCB
      retentate (36.6% solids) with partially skimmed milk (11.2% solids) and cream
      (34.6% fat). Control milk (11.0% solids) was standardized by blending partially
      skimmed milk with cream. Cheese functionality was assessed using dynamic low
      amplitude oscillatory rheology, UW Meltprofiler (degree of flow after heating to
      60 degrees C), and performance of cheese on pizza. Initial trials with SCB
      fortified cheeses resulted in approximately 4 to 5% higher moisture (51 to 52%)
      than control cheese (approximately 47%). In subsequent trials, procedures were
      altered to obtain similar moisture content in all cheeses. Fat recoveries were
      significantly lower in RO- and EVAP-SCB cheeses than in control or UF-SCB
      cheeses. Nitrogen recoveries were not significantly different but tended to be
      slightly lower in control cheeses than the various SCB cheeses. Total PL
      recovered in SCB cheeses ( approximately 32 to 36%) were lower than control (
      approximately 41%), even though SCB is high in PL. From the rheology test, the
      loss tangent curves at temperatures > 40 degrees C increased as cheese aged up to
      a month and were significantly lower in SCB cheeses than the control, indicating
      lower meltability. Degree of flow in all the cheeses was similar regardless of
      the treatment used, and as cheese ripened, it increased for all cheeses.
      Trichloroacetic acid-soluble N levels were similar in the control and SCB
      fortified cheese. On baked pizza, cheese made from milk fortified with UF-SCB
      tended to have the lowest amount of free oil, but flavor attributes of all
      cheeses were similar. Addition of concentrated SCB to standardize cheesemilk for
      pizza cheese did not adversely affect functional properties of cheese but
      increased cheese moisture without changes in manufacturing procedure.

PMID- 17517708
TI  - Characterization of Italian cheeses ripened under nonconventional conditions.
AB  - Four Italian cheeses (Casciotta di Urbino, Barricato San Martino, Vento d'Estate,
      and Ubriaco di Raboso) nonconventionally ripened under different plant materials
      (walnut leaves, herbs, hay, and wine by-products, respectively) were compared for
      compositional, microbiological, biochemical, and volatile profile
      characteristics. Mean values for gross composition were rather similar. Because
      primary starters were not used for manufacture, the endogenous lactic acid
      bacteria were mainly present (7.0 to 9.0 log10 cfu/g). Except for Lactobacillus
      paracasei and Leuconostoc mesenteroides, which were commonly identified in 3
      cheeses, Lactococcus lactis, Enterococcus sanguinicola, Lactobacillus brevis,
      Enterococcus durans/Enterococcus faecium, Lactobacillus plantarum, and Weissella
      cibaria/Weissella confusa were variously found in the 4 cheeses. Random
      amplification of polymorphic DNA-PCR analysis showed the biodiversity among the
      strains, and the species of lactobacilli were in part grouped according to their
      origin. As shown by the principal component analysis of reverse-phase fast
      protein liquid chromatography data for the pH 4.6-soluble fractions and by the
      determination of free AA, the secondary proteolysis of Barricato San Martino and
      Vento d'Estate mainly differed from the other 2 cheeses. Purge-and-trap and solid
      phase microextraction were coupled with gas chromatography-mass spectrometry to
      determine volatile compounds. Vento d'Estate showed the highest levels of almost
      all chemical classes, and Casciotta di Urbino was characterized by a very low
      level of volatile components. Esters, ketones, and terpenes were the chemical
      classes that mainly differentiated the cheeses. Several volatile compounds seemed
      to be released directly from the plant materials used for ripening, especially
      terpenes for Vento d'Estate cheese. The lowest level of volatile free fatty acids
      was found in Casciotta d'Urbino, in which rennet paste was not used during
      manufacture. The highest concentration of free fatty acids, especially butyric
      and caproic acids, was found in Vento d'Estate cheese.

PMID- 17517709
TI  - Solubilized micellar calcium induced low methoxyl-pectin aggregation during milk
      acidification.
AB  - Low methoxyl (LM) pectin was combined with 3-kDa molecular weight cut-off
      permeates from milk subjected to pH 6.7 to 5 and 7 degrees C or 40 degrees C with
      the objective of studying the effect of solubilized micellar calcium on
      viscoelastic properties of LM-pectin-milk mixes. Lowering the pH of skim milk
      with hydrochloric acid during ultrafiltration gradually promoted permeates to
      exhibit gel-like behavior when combined with LM-pectin. The onset of the gel-like
      behavior (G' > 1) occurred at a higher pH when permeates were obtained from milk
      filtered at 7 degrees C compared with 40 degrees C. As pH value during
      ultrafiltration approached 5 and regardless of temperature, G' for permeate
      pectin mixes approached the same values (approximately 70 Pa) as G' for skim milk
      pectin mixes. In all cases G' was highly correlated with free calcium
      concentration (r > 0.95). The gradual acidification of skim milk-LM-pectin using
      glucono-delta-lactone, promoted a sharp increase in storage modulus as pH
      approached 5.2 and a maximum G' increment (DeltaG') at pH approximately 4.9. From
      pH 4.9 to 4, G' continued to increase but at smaller increments. It was concluded
      that LM-pectin-casein micelle interaction in milk is a 2-step process: 1)
      solubilized micellar calcium dependent pectin-pectin interaction as pH approaches
      5.0 to 4.9, and 2) pectin-casein micelle interaction in the 5.0-4.9 to 4.0 pH
      range.

PMID- 17517710
TI  - Development of new probiotics by strain combinations: is it possible to improve
      the adhesion to intestinal mucus?
AB  - We evaluated the ability of commercial probiotic strains (Lactobacillus rhamnosus
      GG, L. rhamnosus LC705, Bifidobacterium breve 99, and Propionibacterium
      freudenreichii ssp. shermanii JS) to adhere alone or in different combinations to
      immobilized mucus. Probiotic combinations were clearly able to enhance the
      adhesion of L. rhamnosus GG, L. rhamnosus LC705, and P. freudenreichii ssp.
      shermanii JS. For L. rhamnosus GG and P. freudenreichii JS, all the combinations
      significantly improved adhesion to intestinal mucus, from 29.7 to 34.9% and from
      1.9 to 2.3%, respectively. The adhesion of L. rhamnosus LC705 was improved from 0
      to 46.4%. The adhesion of B. breve 99 was improved only in combination with L.
      rhamnosus GG and P. freudenreichii JS. Our results suggest that probiotic
      combinations could increase the beneficial health effects as compared with
      individual strains. Combinations of probiotic strains may therefore have
      synergistic adhesion effects, and such combinations also should be assessed in
      clinical studies.

PMID- 17517711
TI  - Occurrence of polycyclic aromatic hydrocarbons in artisanal Palmero cheese smoked
      with two types of vegetable matter.
AB  - Palmero cheese is a fresh smoked cheese from the Isle of Palma (Canary Islands),
      manufactured with goat's milk. To guarantee its safety, the occurrence of
      polycyclic aromatic hydrocarbons (PAH) in artisanal Palmero cheese smoked with 2
      types of vegetable matter (almond shells and dry prickly pear) was studied. The
      determination of PAH includes extraction and clean-up steps, followed by
      separation, identification, and quantification of PAH by gas chromatography-mass
      spectrometry in selected ion-monitoring mode. The most abundant PAH are those
      with 2 and 3 aromatic rings. Although the highest total PAH concentrations
      corresponded to the cheeses smoked with almond shells, the degree of PAH
      contamination of the cheeses studied was lower than that found in other cheeses
      smoked in the traditional way. The nature of the vegetable material used for
      smoking seemed to have an influence on the type of PAH formed, especially on
      alkylderivatives and some light PAH. However, despite the artisanal, and
      consequently variable, production process of these cheeses, many similarities
      have been found among their PAH profiles. In fact, relatively constant
      relationships are observed between the concentrations of certain pairs of PAH.
      Benzo(a)pyrene was only present in 2 samples, and in much lower concentrations
      than the maximum allowed legal limits. Therefore, according to the results
      obtained, it appears that it is possible to obtain a safe product without
      renouncing the artisanal character or the sensory properties of this type of
      cheese.

PMID- 17517712
TI  - Abundance and phosphorylation state of translation initiation factors in mammary
      glands of lactating and nonlactating dairy cows.
AB  - To test if control of mRNA translation is involved in the increase in protein
      synthesis by mammary glands during lactation, cellular contents and
      phosphorylation states of translation factors and their upstream regulators were
      measured in mammary parenchyma from 12 nonpregnant dairy cows. For a 42-d period,
      6 cows in late lactation continued to be milked (L) and 6 at the same stage of
      lactation were dried off (NL). All cows were then slaughtered and mammary glands
      and tissue samples obtained. Alveoli and lobules tended to be larger in L cows.
      Mammary parenchymal mass, cell number, cell size, and RNA, DNA, and protein
      contents were greater in L cows. Increases (3.1- and 1.8-fold) in the abundance
      of active, phosphorylated ribosomal protein S6 and its kinase, S6K1,
      respectively, in L vs. NL parenchyma indicated an ability to sustain greater
      rates of synthesis of translational machinery, which was also evident in the 102%
      increase in parenchymal RNA:DNA between the 2 groups. Cellular abundances of the
      main eukaryotic translation initiation factors (eIF), eIF2 and eIF4E, were 2.6-
      and 3-fold greater, respectively, in L cows. That these differences were greater
      than the 102% greater RNA:DNA in L mammary parenchyma suggests an elevated
      translational efficiency in L glands. Abundance of phosphorylated rpS6 was not
      different between mammary parenchyma and liver, whereas eIF2alpha was 50% greater
      in mammary tissue. In semimembranosus muscle, abundances of phosphorylated rpS6
      and eIF2alpha were 3 to 4 times lower than in mammary parenchyma. In both L and
      NL mammary glands, 11% of eIF2alpha was in the inhibitory, phosphorylated form
      and 48 to 60% of eIF4E was complexed with its binding protein, 4EBP1. It is
      concluded that up-regulation of initiation of mRNA translation occurs in the
      fully differentiated milk secretory cell and that, where crucial initiation
      factors are not present in a maximally active form, the initiation rate might be
      flexible in response to external stimuli.

PMID- 17517713
TI  - Induction of hyperlipidemia by intravenous infusion of tallow emulsion causes
      insulin resistance in Holstein cows.
AB  - The objective was to test whether the induction of elevated blood nonesterified
      fatty acids (NEFA) by i.v. infusion of a tallow emulsion altered glucose
      tolerance and responsiveness to insulin in Holstein cows. Six non-lactating,
      nongestating Holstein cows were assigned to a crossover design. One cow was
      excluded before initiation of the experiment because of complications from
      mastitis. Treatments consisted of 11-h i.v. infusions of saline (control) or a
      20% (wt/vol) triacylglycerol (TG) emulsion derived from tallow (tallow) to
      elevate plasma NEFA. Each period consisted of two 11-h infusions (INF1 and INF2),
      separated by 1 d in which cows were not infused. Intravenous glucose tolerance
      tests (IVGTT) and insulin challenges (IC) were performed 8 h after initiation of
      INF1 and INF2, respectively. The infusion of treatments continued during the 3 h
      of sampling for IVGTT and IC. Cows were fed every 4 h at a rate to meet energy
      requirements for 5 d prior to each period, and every 2 h during the first 8 h of
      infusions. Infusion of tallow induced hyperlipidemia by increasing plasma NEFA
      (295 +/- 9 vs. 79 +/- 7 microEq/L), serum TG (41.0 +/- 6 vs. 11.4 +/- 4.4 mg/dL),
      and glycerol (0.81 +/- 0.09 vs. 0.23 +/- 0.1 mg/dL) concentrations during INF1.
      During INF2, tallow treatment increased plasma NEFA (347 vs. 139 +/- 18
      microEq/L), serum TG (20.8 +/- 4.6 vs. 13.1 +/- 2.3 mg/dL), and glycerol (0.88 +/
      0.04 vs. 0.31 +/- 0.02 mg/dL) concentrations. Induction of hyperlipidemia
      impaired glucose clearance during IVGTT, despite the greater endogenous insulin
      response to the glucose infusion, leading to a lower insulin sensitivity index
      [0.29 vs. 1.88 +/- 0.31 x 10(-4) min(-1)/(microIU/mL)]. Accordingly,
      hyperlipidemia impaired glucose clearance during IC (1.58 vs. 2.72 %/min),
      reflecting lower responsiveness to insulin. These data show that induction of
      hyperlipidemia causes insulin resistance in Holstein cows by impairing both
      sensitivity and maximum responsiveness to insulin. The induction of insulin
      resistance by TG, NEFA, or both may increase the availability of glucogenic
      nutrients to the periparturient dairy cow. Yet excessive elevation of NEFA may
      potentially lead adipocytes to become more insulin resistant, further increasing
      plasma NEFA concentration and the risk of metabolic disorders.

PMID- 17517714
TI  - Bacillus cereus spores during housing of dairy cows: factors affecting
      contamination of raw milk.
AB  - The contamination of raw milk with Bacillus cereus spores was studied during the
      indoor confinement of dairy cattle. The occurrence of spores in fresh and used
      bedding material, air samples, feed, feces, and the rinse water from milking
      equipment was compared with the spore level in bulk tank milk on 2 farms, one of
      which had 2 different housing systems. A less extensive study was carried out on
      an additional 5 farms. High spore concentrations of >100 spores/L in the raw milk
      were found on 4 of the farms. The number of spores found in the feed, feces, and
      air was too small to be of importance for milk contamination. Elevated spore
      contents in the rinse water from the milking equipment (up to 322 spores/L) were
      observed and large numbers of spores were found in the used bedding material,
      especially in free stalls with >5 cm deep sawdust beds. At most, 87,000 spores/g
      were found in used sawdust bedding. A positive correlation was found between the
      spore content in used bedding material and milk (r = 0.72). Comparison of the
      genetic fingerprints obtained by the random amplified polymorphic DNA PCR of
      isolates of B. cereus from the different sources indicated that used bedding
      material was the major source of contamination. A separate feeding experiment in
      which cows were experimentally fed B. cereus spores showed a positive
      relationship between the number of spores in the feed and feces and in the feces
      and milk (r = 0.78). The results showed that contaminated feed could be a
      significant source of spore contamination of raw milk if the number of spores
      excreted in the feces exceeded 100,000/g.

PMID- 17517715
TI  - Methane emissions from dairy cows measured using the sulfur hexafluoride (SF6)
      tracer and chamber techniques.
AB  - Our study compared methane (CH4) emissions from lactating dairy cows measured
      using the sulfur hexafluoride (SF6) tracer and open-circuit respiration chamber
      techniques. The study was conducted using 16 lactating Holstein-Friesian cows. In
      each chamber, the cow was fitted with the SF6 tracer apparatus to measure total
      CH4 emissions, including emissions from the rectum. Fresh ryegrass pasture was
      harvested daily and fed ad libitum to each cow with a supplement of 5 kg of
      grain/d. The CH4 emissions measured using the SF6 tracer technique were similar
      to those using the chamber technique: 331 vs. 322 g of CH4/d per cow. The
      accuracy of the SF6 tracer technique was indicated by considering the ratio of
      the CH4 emission measured using the SF6 tracer to the emission measured using the
      chamber for each cow on each day. The calculated ratio of 102.3% (SE = 1.51) was
      not different from 100%. A higher variability within cow between days was found
      for the SF6 tracer technique [coefficient of variation (CV) = 6.1%] than for the
      chamber technique (CV = 4.3%). The variability among cows was substantially
      higher than within cows, and was higher for the SF6 technique (CV = 19.6%) than
      for the chamber technique (CV = 17.8%). Our CH4 emission data were compared with
      whole-animal chamber studies conducted in Canada and Ireland. In the Canadian
      study the SF6 technique did not measure CH4 emissions from the rectum and
      emissions were 8% lower than those measured using the chamber, indicating that
      emissions from the rectum may be greater than previously measured (1%). The
      relationship between CH4 emission and dry matter intake was examined for our data
      and for that reported in the Canadian study. There was a difference in the slopes
      of the regressions derived from our data and that from Canada; 17.1 vs. 20.8 g of
      CH4/kg of dry matter intake. A difference between the 2 locations was expected
      based on the difference in diet composition for these 2 studies. The SF6 tracer
      technique is reasonably accurate for inventory purposes and for evaluating the
      effects of mitigation strategies on CH4 emissions.

PMID- 17517716
TI  - Contribution of macrophages to proteolysis and plasmin activity in ewe bulk milk.
AB  - A total of 225 bulk sheep milk samples were collected from 5 intensively managed
      flocks during early, mid, and late lactation to assess the contribution of
      macrophages to the regulation of the plasmin-plasminogen system. Samples were
      analyzed for composition, somatic cell counts, milk renneting characteristics,
      and for plasmin (PL), plasminogen (PG), and plasminogen activators (PA)
      activities. Isolation of macrophages from milk was performed using a magnetic
      positive separation and mouse antiovine macrophage antibody; separated cells were
      lysed by several freeze-thaw cycles, and activity of urokinase PA (u-PA) was
      determined. Plasmin activity decreased during lactation (42.06 +/- 0.66, early;
      31.29 +/- 0.66, mid; 28.19 +/- 0.66 U/mL, late). The reduction in PL activity
      recorded in the mid and late lactation milk matched the increase in PG:PL ratio.
      The activity of PA increased throughout lactation; the highest value being
      recorded in the late lactation milk (260.20 +/- 8.66 U/mL). Counts of isolated
      and concentrated macrophages were higher in early and mid lactation milk (3.89 +/
      0.08 and 3.98 +/- 0.08 log10 cells/mL, respectively) than in late lactation milk
      (3.42 +/- 0.08 log10 cells/mL). Stage of lactation did not influence the activity
      of u-PA detected in isolated macrophages. The activity of u-PA associated with
      isolated milk macrophages only minimally contributed to total PA activity
      detected in milk. Proteolytic enzymes, associated with isolated macrophages, act
      on alpha-casein hydrolysis, as shown by urea-PAGE electrophoresis analysis.
      Somatic cell counts did not exceed 600,000 cells/mL, and this threshold can be
      considered a good index of health status of the flock and of the ability of milk
      to being processed. Our results lend support to the hypothesis that macrophages
      in ewe bulk milk from healthy flocks only slightly contribute to the activation
      of the PL-PG system.

PMID- 17517717
TI  - Behavior, milk yield, and milk composition of machine-and hand-milked Murgese
      mares.
AB  - A 25-d trial was performed to assess the effects of machine and hand milking on
      behavior, and milk yield and composition of mares; the trial involved 8 Murgese
      mares. Milk yield was higher (7.69 vs. 4.91 kg) and milking time was shorter
      (1.80 vs. 5.40 min) in machine-milked than in hand-milked mares. Machine milking
      of mares also resulted in a greater fat content of milk (1.63%) than did hand
      milking (1.06%). Milking system did not affect casein content, nitrogen
      fractions, or somatic cell counts. No differences in behavioral activities and in
      response to humans emerged. Results indicate that machine milking of mares could
      improve the yield and gross composition of horse milk, without adverse
      consequences on mare behavior and response to humans.

PMID- 17517718
TI  - Efficacy of a lactoferrin-penicillin combination to treat {beta}-lactam-resistant
      Staphylococcus aureus mastitis.
AB  - The efficacy of intramammary (IM) treatments containing penicillin G (PG) alone
      or a combination of PG and bovine lactoferrin (bLF) was evaluated using a model
      of experimentally induced chronic bovine mastitis caused by a clinical isolate of
      Staphylococcus aureus highly resistant to beta-lactam antibiotics. First, we
      confirmed that this strain could cause mastitis and infection could not be cured
      with PG alone. In a second trial, chronic mastitis was induced in 19 late
      lactating cows by injecting a low dose of Staph. aureus through the teat canal of
      all quarters. After 15 d, cows with stable infections in their 4 quarters had
      their mammary quarters randomly assigned, within cow, to 1 of 4 IM treatments as
      follows: 1) citrate buffer, 2) 100,000 IU of PG, (3) 1 g of bLF, or 4) 1 g of bLF
      + 100,000 IU of PG. Treatments were repeated twice a day for 5 d. A third trial
      was undertaken to investigate the effect of an extended therapy on chronic
      mastitis acquired in a previous lactation. One month before dry-off, 20 gravid
      cows regrouped by dates of calving were infected in their 4 quarters. Once
      infections were established, cows were dried off abruptly. After calving, aseptic
      milk samples were collected separately from all quarters for 4 wk to monitor
      infection. Mammary quarters from enrolled cows were then randomly assigned,
      within cow, to 1 of 2 treatments as follows: 1) 100,000 IU of PG or 2) 250 mg of
      bLF + 100,000 IU of PG. Treatments were administered IM twice a day for 7 d. For
      all trials, milk samples were taken to monitor bacterial concentration and
      somatic cell count. Bacteriological cure rate was determined using milk samples
      taken 3 and 4 wk after initiation of treatments. For the second trial, cure rate
      was null for control quarters, 11.1% for bLF, 9.1% for PG, and 45.5% for the bLF
      + PG combination. For cows infected in their previous lactation, cure rate was
      higher for the bLF + PG combination (33.3%) compared with PG alone (12.5%). In
      conclusion, bLF added to PG is an effective combination (i.e., 3- to 5-times
      higher cure rate) for the treatment of stable Staph. aureu infections highly
      resistant to beta-lactam antibiotics.

PMID- 17517719
TI  - The effect of subclinical ketosis in early lactation on reproductive performance
      of postpartum dairy cows.
AB  - Data generated from 796 Holstein cows enrolled in a clinical trial to investigate
      the health effect of a monensin controlled release capsule were analyzed to
      investigate the association between circulating serum beta-hydroxybutyrate (BHBA)
      concentration in the peri-parturient period and subsequent reproductive
      performance. Overall, accounting for both repeated measures within cow and
      clustering at the herd level, non-pregnant cows after first insemination tended
      to have increased circulating BHBA concentrations from 3 wk before calving to 9
      wk after calving relative to pregnant cows. Including the interaction between the
      week of sample collection and pregnancy outcome, non-pregnant cows had higher
      circulating BHBA concentrations in the second week after calving than cows
      diagnosed pregnant after first artificial insemination. Within individual weeks,
      cows with circulating BHBA concentrations > or =1,000 micromol/L in the first
      week postpartum were less likely to be diagnosed pregnant after first
      insemination. In the second week postpartum, the cows with circulating BHBA
      concentrations > or =1,400 micromol/L were significantly less likely to be
      pregnant after first artificial insemination. A dose response relationship was
      found when a comparison of the probability of pregnancy after first insemination
      and duration of elevated circulating ketone bodies was investigated. The
      probability of pregnancy was reduced by 20% in cows diagnosed subclinically
      ketotic in either the first or second week postpartum. Nevertheless, cows above
      the subclinical ketosis threshold in both the first and second week postpartum
      were 50% less likely to be pregnant after first insemination. Similarly, the
      median time to pregnancy increased in cows experiencing elevated BHBA
      concentrations in either (124 d) or both (130 d) the first and second week
      postpartum relative to cows never experiencing elevated BHBA concentrations (108
      d). To further investigate this, the effect of elevated circulating BHBA was
      permitted to vary with time. The effect decreased with time, such that the daily
      probability of pregnancy increased similar to nonsubclinically ketotic cows by
      approximately 160 d in milk. From this analysis, both the relative circulating
      concentration of BHBA and the duration of elevated circulating BHBA were
      negatively associated with the probability of pregnancy at first service.

PMID- 17517720
TI  - Effect of stillbirths on dam survival and reproduction performance in Holstein
      dairy cows.
AB  - The objectives of this study were to evaluate the effect of stillbirth on
      survival and reproductive performance of lactating dairy cows. Data were
      collected from 2 different regions of the US calving-ease scores (CES) were
      recorded by farm personnel on a scale of 1 (no problem) to 5 (extreme
      difficulty). Stillbirths were recorded by farm personnel. The final analysis
      included 13,608 calvings of which 93.4% were live calves and 6.6% stillbirths. An
      increasing or decreasing trend in the incidence of stillbirth by parity and by
      CES was analyzed by Cochran-Armitage trend tests. A significant decreasing trend
      in the incidence of stillbirth by parity group was detected. The incidence of
      stillbirth increased as the CES increased. The incidence of stillbirths was 3.6,
      11.2, 25.9, and 60.1% for CES score 1, 2, 3, and 4, respectively. Dam survival in
      the herd and reproductive performance were analyzed by the Cox proportional
      hazards model. Variables that decreased dam survival time were stillbirths,
      primiparity, and CES of 3 and 4. The variables that reduced reproductive
      performance were stillbirths, multiparity, male calves, and CES of 3 and 4. Cows
      that had stillbirths had significantly increased risk of culling/death throughout
      the lactation and increased median days open by 88 d compared with cows that had
      live calves. In conclusion, losses from stillbirths are far greater than just the
      value of the calf.

PMID- 17517721
TI  - Rectal temperature, calving-related factors, and the incidence of puerperal
      metritis in postpartum dairy cows.
AB  - The objectives of this study were as follows: 1) to evaluate the association
      among abnormal calving, parity, and season on the incidence of puerperal metritis
      (PM) and clinical endometritis (CE) during d 3 to 13 and 20 to 30 postpartum,
      respectively; 2) to describe the rectal temperature (RT) of cows with PM before
      diagnosis; and 3) to document associations among PM, CE, and reproductive
      performance in lactating dairy cows. This study followed a prospective
      observational study design. Cows were classified as having an abnormal calving
      status (AC), i.e., cows calving with dystocia, twins, retained fetal membranes,
      or some combination of these conditions, and having a normal calving status (NC).
      Daily RT was recorded from d 3 to 13 postpartum for all cows, and health
      examinations were performed on cows that appeared not well. A total of 450
      calvings were evaluated. Cows with an AC had greater odds of PM than cows with NC
      [adjusted odds ratio (AOR) = 4.8; 95% confidence interval (CI) = 2.9 to 8.0). A
      season by parity interaction showed that primiparous cows that calved during the
      warm season had lower AOR of PM than during the cool season (0.24; 95% CI = 0.09
      to 0.62), whereas multiparous cows did not have seasonal effects on PM (1.43; 95%
      CI = 0.65 to 3.18). Cows with AC have greater AOR for CE than cows with NC (2.8;
      95% CI = 1.7 to 4.9), and greater AOR of CE were detected in cows diagnosed with
      PM than in cows without PM (2.2; 95% CI = 1.1 to 3.9). Rectal temperature in cows
      with PM increased significantly 24 h before diagnosis of PM, reaching 39.2 +/-
      0.05 degrees C on the day of diagnosis. In cows with PM and fever at diagnosis,
      the RT began to increase from 72 to 48 h before the diagnosis of PM and continued
      to increase to 39.7 +/- 0.09 degrees C on d 0 (day of diagnosis). Nonetheless,
      cows with PM without fever at diagnosis had no daily increases in RT before
      diagnosis of PM. Still, the RT on d 0 was different from cows without PM. Cows
      without PM had a stable RT (38.6 +/- 0.01 degrees C). There were no detected
      differences in first-service conception risk or cumulative pregnancy risk by 150
      d postpartum between cows with or without PM. Still, a season effect on first
      service conception AOR (warm vs. cool = 0.98; 95% CI = 0.18 to 0.72) and
      accumulated pregnancy AOR by 150 d postpartum was detected (warm vs. cool = 0.18;
      95% CI = 0.10 to 0.33).

PMID- 17517722
TI  - Risk factors for changing test classification in the Danish surveillance program
      for Salmonella in dairy herds.
AB  - A surveillance program in which all cattle herds in Denmark are classified into
      Salmonella infection categories has been in place since 2002. Dairy herds were
      considered test negative and thus most likely free of infection if Salmonella
      antibody measurements were consistently low in bulk tank milk samples collected
      every 3 mo. Herds were considered test positive and thus most likely infected if
      the 4-quarter moving average bulk tank milk antibody concentration was high or if
      there was a large increase in the most recent measurement compared with the
      average value from the previous 3 samples. The objective of this study was to
      evaluate risk factors for changing from test negative to positive, which was
      indicative of herds becoming infected from one quarter of the year to the next,
      and risk factors for changing from test positive to negative, which was
      indicative of herds recovering from infection between 2 consecutive quarters of
      the year. The Salmonella serotypes in question were Salmonella Dublin or other
      serotypes that cross-react with the Salmonella Dublin antigen in the ELISA (e.g.,
      some Salmonella Typhimurium types). Two logistic regression models that accounted
      for repeated measurements at the herd level and controlled for herd size and
      regional effects were used. Data from 2003 was used for the analyses. A change
      from test negative to positive occurred in 2.0% of the quarterly observations (n
      = 21,007) from test negative dairy herds. A change from test positive to negative
      occurred in 10.0% of quarterly observations (n = 6,168) available from test
      positive dairy herds. The higher the number of test-positive neighbor herds in
      the previous year-quarter, the more likely herds were to become test positive for
      Salmonella. The number of purchased cattle from test-positive herds was also
      associated with changing from test negative to positive. The bigger the herd, the
      more likely it was to change from negative to test positive. The effect of herd
      size on recovery was less clear. Large herds consisting mainly of large breeds or
      having test-positive neighbors in a 2-km radius were less likely to change from
      test positive to negative, whereas the breed and neighbor factors were not found
      to be important for small herds. Organic production was associated with remaining
      test positive, but not with becoming test positive. The results emphasize the
      importance of external and internal biosecurity measures to control Salmonella
      infections.

PMID- 17517723
TI  - Altering physically effective fiber intake through forage proportion and particle
      length: chewing and ruminal pH.
AB  - Alfalfa silages varying in theoretical chop length and diets high and low in
      forage proportion were used to evaluate whether increasing the physically
      effective (pe) neutral detergent fiber (NDF) content of dairy cow diets reduces
      the risk of acidosis. The experiment was designed as a replicated 4 x 4 Latin
      square using 8 ruminally cannulated lactating dairy cows. Treatments were
      arranged in a 2 x 2 factorial design; 2 forage particle lengths (FPL) of alfalfa
      silage (short and long) were combined with low (35:65) and high (60:40)
      forage:concentrate (F:C) ratios [dry matter (DM) basis]. Dietary peNDF content
      (DM basis) was determined from the sum of the proportion of dietary DM retained
      on either the 2 sieves (8 and 19 mm) or the 3 sieves (1.18, 8, and 19 mm) of the
      Penn State Particle Separator multiplied by the NDF content of the diet. The
      dietary peNDF contents ranged from 9.6 to 19.8% using 2 sieves, or from 28.6 to
      34.0% using 3 sieves. Intake of peNDF was increased by increasing both the F:C
      ratio and the FPL of the diets. However, F:C ratio and FPL affected chewing
      activity differently; increasing F:C ratio increased chewing time but increasing
      FPL only increased chewing when a high-forage diet was fed. Mean ruminal pH was
      increased by 0.5 and 0.2 units with increasing F:C ratio and FPL, respectively.
      Cows fed the low F:C diet had > 10 or 7 h daily in which ruminal pH was below 5.8
      or 5.5, respectively, compared with 1.2 and 0.1 h for cows fed the high F:C ratio
      diet. Increased F:C ratio reduced ruminal VFA concentration from 135 to 121 mM
      but increased the acetate:propionate ratio from 1.82 to 3.13. Dietary peNDF
      content when measured using 2 sieves was positively correlated to chewing time (r
      = 0.61) and mean ruminal pH (r = 0.73), and negatively correlated to the time
      that pH was below 5.8 or 5.5 (r = -0.46). This study shows that the risk of
      ruminal acidosis is high for cows fed a low F:C diet, particularly when finely
      chopped silage is used. Intake of dietary peNDF is a good indicator of ruminal pH
      status of dairy cows. Increasing the proportion of forage in the diet helps
      prevent ruminal acidosis through increased chewing time, a change in meal
      patterns, and decreased ruminal acid production. Increasing FPL elevates ruminal
      pH, but in low-forage diets increased FPL does not completely alleviate subacute
      acidosis because the fermentability of the diet is high and changes in chewing
      activity are marginal.

PMID- 17517724
TI  - Enhancing in vitro degradation of alfalfa hay and corn silage using feed enzymes.
AB  - A series of in vitro fermentation experiments was performed to assess the effects
      of 4 feed enzyme products (FE) that varied in enzymatic activities on the
      degradation of alfalfa hay and corn silage. The FE contained a range of
      endoglucanase, exoglucanase, xylanase, and protease activities, and a range of
      dose rates (DR) was used. The objective of the study was to identify effective
      formulations and optimum DR, and to establish if combining FE would further
      improve fiber degradation. For alfalfa hay, quadratic increases in gas production
      and degradation of dry matter (DM) and fiber were observed for all FE, with
      maximum responses at low to medium DR. For corn silage, none of the FE increased
      gas production or DM degradation, but all FE increased NDF degradation, with
      optimum DR in the low to medium range. The proteolytic enzyme papain improved
      fiber degradation of alfalfa hay and corn silage in a manner similar to that
      observed for polysaccharidase FE. Among the polysaccharidase FE, added activities
      of endoglucanase and exoglucanase were positively correlated with improvement in
      neutral detergent fiber (NDF) degradability of corn silage, whereas only added
      endoglucanase activity tended to be correlated with improvement in NDF
      degradability of alfalfa hay. Combining effective polysaccharidase FE further
      improved fiber degradation of both forages, with greater improvements for corn
      silage. Combining polysaccharidase and proteolytic FE further improved NDF
      degradation of corn silage, but not alfalfa hay. Combination treatments generally
      resulted in additive effects with increases in fiber degradation equal to the sum
      of the improvements for the individual enzyme components. Improved fiber
      degradation of corn silage was associated with decreased acetate to propionate
      ratios. Enzyme products that improve in vitro degradation of forages may have the
      potential to improve lactational performance of dairy cows.

PMID- 17517725
TI  - Effect of grains differing in expected ruminal fermentability on the productivity
      of lactating dairy cows.
AB  - The objective of the study was to evaluate the effect of barley and corn grains
      differing in expected fermentability in the rumen on dry matter intake (DMI) and
      productivity of lactating dairy cows. Twenty-two multiparous and 9 primiparous
      lactating Holstein cows (94 +/- 29 d in milk; mean +/- SD) were used in a 3 x 3
      Latin square design with 21-d periods. Experimental diets contained approximately
      40% of dietary dry matter as steam-rolled barley, using a lot of cultivar Dillon
      or cultivar Xena, or a corn mixture (CM) containing 87.5% dry ground corn, 11.4%
      beet pulp, and 1.1% urea (dry matter basis). Starch concentration of the grain
      sources was 50.0, 58.7, and 60.4% and in vitro 6-h starch digestibility was 73.5,
      78.0, and 71.0%, respectively, for Dillon, Xena, and CM. All diets were
      formulated to contain 19.4% crude protein and 25.3% forage neutral detergent
      fiber. Dry matter intake (23.6 vs. 21.6 kg/d) and yields of milk (40.4 vs. 37.4
      kg/d), milk protein (1.20 vs. 1.12 kg/d), and milk lactose (1.85 vs. 1.74 kg/d)
      were higher for cows fed CM than for cows fed barley. Although DMI was similar
      for cows fed Xena and Dillon (21.9 vs. 21.4 kg/d), cows fed Xena had higher
      yields of milk (38.5 vs. 36.2 kg/d), milk protein (1.18 vs. 1.07 kg/d), and milk
      lactose (1.80 vs. 1.69 kg/d) than cows fed Dillon. However, milk fat
      concentration tended to be higher (3.47 vs. 3.23%) for cows fed Dillon than Xena.
      Plasma glucose and nonesterified fatty acid concentrations were not affected by
      treatment, but plasma insulin concentration was higher for cows fed Xena compared
      with those fed Dillon (8.50 vs. 5.91 microIU/mL). Greater milk production for
      cows fed CM can be attributed to greater DMI. Feeding barley that was lower in
      starch concentration and ruminal starch fermentability (Dillon) did not increase
      DMI compared with feeding barley that was higher in starch concentration and
      ruminal starch fermentability (Xena). Reducing ruminal starch degradation of
      barley grain may not improve the productivity of lactating dairy cows.

PMID- 17517726
TI  - Selection of barley grain affects ruminal fermentation, starch digestibility, and
      productivity of lactating dairy cows.
AB  - The objective of this study was to evaluate the effects of 2 lots of barley grain
      cultivars differing in expected ruminal starch degradation on dry matter (DM)
      intake, ruminal fermentation, ruminal and total tract digestibility, and milk
      production of dairy cows when provided at 2 concentrations in the diet. Four
      primiparous ruminally cannulated (123 +/- 69 d in milk; mean +/- SD) and 4
      multiparous ruminally and duodenally cannulated (46 +/- 14 d in milk) cows were
      used in a 4 x 4 Latin Square design with a 2 x 2 factorial arrangement of
      treatments with 16-d periods. Primiparous and multiparous cows were assigned to
      different squares. Treatments were 2 dietary starch concentrations (30 vs. 23% of
      dietary DM) and 2 lots of barley grain cultivars (Xena vs. Dillon) differing in
      expected ruminal starch degradation. Xena had higher starch concentration (58.7
      vs. 50.0%) and greater in vitro 6-h starch digestibility (78.0 vs. 73.5%)
      compared with Dillon. All experimental diets were formulated to supply 18.3%
      crude protein and 20.0% forage neutral detergent fiber. Dry matter intake and
      milk yield were not affected by treatment. Milk fat concentration (3.55 vs.
      3.29%) was greater for cows fed Dillon compared with Xena, but was not affected
      by dietary starch concentration. Ruminal starch digestion was greater for cows
      fed high-starch diets compared with those fed low-starch diets (4.55 vs. 2.49
      kg/d), and tended to be greater for cows fed Xena compared with those fed Dillon
      (3.85 vs. 3.19 kg/d). Ruminal acetate concentration was lower, and propionate
      concentration was greater, for cows fed Xena or high-starch diets compared with
      cows fed Dillon or low-starch diets, respectively. Furthermore, cows fed Xena or
      high-starch diets had longer duration that ruminal pH was below 5.8 (6.6 vs. 4.0
      and 6.4 vs. 4.2 h/d) and greater total tract starch digestibility (94.3 vs. 93.0
      and 94.3 vs. 93.0%) compared with cows fed Dillon or low-starch diets,
      respectively. These results demonstrate that selection of barley grain can affect
      milk fat production and rumen fermentation to an extent at least as great as
      changes in dietary starch concentration.

PMID- 17517727
TI  - Effects of the method of conservation of timothy on nitrogen metabolism in
      lactating dairy cows.
AB  - Six ruminally and duodenally cannulated lactating primiparous Holstein cows were
      used to study the effects of different methods of conservation of timothy on N
      metabolism. Cows were assigned randomly to 2 replicated 3 x 3 Latin squares (35-d
      periods). Because of missing data from 2 cows, data were analyzed as a 3 x 4
      Youden square. Diets contained a similar concentrate (44% of total ration on a
      dry matter basis) plus first-cut timothy conserved as hay, or as restrictively
      (formic) or extensively fermented silage (inoc). Crude protein contents were
      10.4, 13.6, and 14.8% for hay, formic, and inoc, respectively. Hay and formic had
      a high soluble carbohydrate content (> or =8.0% of dry matter) and formic and
      inoc had a high soluble protein content (> or =8.0% of dry matter). Haying and
      restricting fermentation resulted in increased efficiency of partition to milk N
      (30.9, 28.2, 24.7% of N intake for hay, formic, and inoc, respectively). Despite
      a 14% lower N intake with hay, no effects of treatments were detected on
      microbial protein synthesis and apparent intestinal digestion of essential AA.
      Haying reduced feed protein degradation in the rumen, whereas this effect was not
      observed when restricting fermentation in the silage. Haying and restricting
      fermentation induced a lipogenic fermentation pattern in the rumen (4.55, 4.23,
      and 3.78 ratio of acetate to propionate for hay, formic, and inoc), but no
      effects on milk fat yield and plasma glucose were observed. Whole-body protein
      metabolism was unaffected by treatments.

PMID- 17517728
TI  - Effects of fescue type and sampling date on the ruminal disappearance kinetics of
      autumn-stockpiled tall fescue.
AB  - Two tall fescue (Festuca arundinacea Schreb.) forages, one an experimental host
      plant/endophyte association containing a novel endophyte (HM4) that produces low
      or nil concentrations of ergot alkaloids, and the other a typical association of
      Kentucky 31 tall fescue and the wild-type endophyte (Neotyphodium coenophialum;
      E+), were autumn-stockpiled following late-summer clipping and fertilization with
      56 kg/ha of N to assess the nutritive value and ruminal disappearance kinetics of
      autumn-stockpiled tall fescue forages. Beginning on December 4, 2003, sixteen 361
      +/- 56.4-kg replacement dairy heifers were stratified by weight and breeding and
      assigned to one of four 1.6-ha pastures (2 each of E+ and HM4) that were strip
      grazed throughout the winter. Pastures were sampled before grazing was initiated
      (December 4), each time heifers were allowed access to a fresh strip (December
      26, January 15, and February 4), and when the study was terminated (February 26).
      For fiber components, there were no interactions between fescue type and sampling
      date for either pregrazed or postgrazed forages. Over sampling dates, neutral
      detergent fiber (NDF; 56.5 to 67.8%), acid detergent fiber (27.7 to 34.9%),
      hemicellulose (28.8 to 34.0%), cellulose (25.0 to 28.1%), and lignin (3.61 to
      10.05%) varied with sampling date, but patterns were almost exclusively
      curvilinear with time. Ruminal disappearance rate of dry matter (DM) was not
      affected by any treatment factor (overall mean for both pregrazed and postgrazed
      forages = 0.050 h(- 1)); similar responses were observed for NDF disappearance
      (overall mean = 0.048 h(- 1)). Interactions of fescue type and sampling date were
      observed for both pregrazed and postgrazed forages with respect to effective
      ruminal disappearance of DM; however, estimates were relatively high for all
      forages (overall mean = 64.0%). Effective disappearance of NDF was relatively
      extensive for all forages (overall mean = 55.4% of NDF). Based on the results of
      this trial, the endophyte status of stockpiled tall fescue forages had little
      practical effect on forage nutritive value and kinetics of ruminal DM or NDF
      disappearance. Overall, autumn-stockpiled tall fescue forages would appear to be
      a legitimate and lower cost alternative to harvested forages, and appear to
      possess suitable nutritional characteristics for developing dairy heifers in the
      Ozark Highlands.

PMID- 17517729
TI  - Diet supplementation with fish oil and sunflower oil to increase conjugated
      linoleic acid levels in milk fat of partially grazing dairy cows.
AB  - The objective of this study was to determine the long-term effect on milk
      conjugated linoleic acid (cis-9, trans-11 CLA) of adding fish oil (FO) and
      sunflower oil (SFO) to the diets of partially grazing dairy cows. Fourteen
      Holstein cows were divided into 2 groups (7 cows/treatment) and fed either a
      control or oil-supplemented diet for 8 wk while partially grazing pasture. Cows
      in group 1 were fed a grain mix diet (8.0 kg/d, DM basis) containing 400 g of
      saturated animal fat (control). Cows in the second group were fed the same grain
      mix diet except the saturated animal fat was replaced with 100 g of FO and 300 g
      of SFO. Cows were milked twice a day and milk samples were collected weekly
      throughout the trial. Both groups grazed together on alfalfa-based pasture ad
      libitum and were fed their treatment diets after the morning and afternoon
      milking. Milk production (30.0 and 31.2 kg/d), milk fat percentages (3.64 and
      3.50), milk fat yield (1.08 and 1.09 kg/d), milk protein percentages (2.97 and
      2.88), and milk protein yield (0.99 and 0.91 kg/d) for diets 1 and 2,
      respectively, were not affected by the treatment diets. The concentrations of cis
      9, trans-11 CLA (1.64 vs. 0.84 g/100 g of fatty acids) and vaccenic acid (5.11
      vs. 2.20 g/100 g of fatty acids) in milk fat were higher for cows fed the oil
      supplemented diet over the 8 wk of oil supplementation. The concentration of cis
      9, trans-11 CLA in milk fat reached a maximum (1.0 and 1.64 g/100 g of fatty
      acids for diets 1 and 2, respectively) in wk 1 for both diets and remained
      relatively constant thereafter. The concentration of vaccenic acid in milk fat
      followed the same temporal pattern as cis-9, trans-11 CLA. In conclusion,
      supplementing the diet of partially grazing cows with FO and SFO increased the
      milk cis-9, trans-11 CLA content, and that increase remained relatively constant
      after 1 wk of oil supplementation.

PMID- 17517730
TI  - Short communication: Absorption of protein and immunoglobulin g in calves fed a
      colostrum replacer.
AB  - A well-managed colostrum program on farms is the most important step in reducing
      disease in neonatal calves. In the last few years, colostrum replacers have
      increased in popularity and are designed to be an alternative to colostrum on
      farms that have poor colostrum quality, limited colostrum reserves, or to break
      the cycle of transmission for certain infectious diseases. However, it is
      important to make sure these products are effective and are capable of providing
      adequate serum immunoglobulin concentrations. The objective of this study was to
      evaluate the efficacy of a commercially available colostrum replacer product in
      dairy calves. Holstein calves from a single dairy were randomly assigned to 1 of
      3 groups at birth. Group 1 (n = 21) calves were given 4 quarts of colostrum via
      esophageal feeder within 3 h of birth and served as the control group for this
      study. Group 2 (n = 21) received 2 packages of a colostrum replacer product, and
      group 3 (n = 21) received 3 packages of the colostrum replacer product within 3 h
      of birth. Blood samples from all calves were collected 24 h after colostrum
      administration and analyzed for serum total protein and IgG concentrations.
      Calves fed fresh colostrum had significantly higher serum total protein levels
      and IgG concentrations compared with calves fed the colostrum replacer product.
      Calves fed the colostrum replacer also had a significantly higher percentage of
      calves with failure of passive transfer (serum IgG <1,000 mg/dL). The colostrum
      replacer product evaluated in this study failed to routinely provide adequate IgG
      concentrations when fed according to label directions.

PMID- 17517731
TI  - Ruminal and intestinal degradability of distillers grains plus solubles varies by
      source.
AB  - Currently in the dairy industry, there is a concern about the variability in the
      nutrient content among sources of distillers grains plus solubles (DG), but
      little research has evaluated the variability in metabolizable AA among sources.
      The ruminal degradability of crude protein (CP) in soybean meal (SBM), dried DG
      from 5 sources (DG1, DG2, DG3, DG4, and DG5), and 1 source of wet DG (WDG) were
      determined using 2 lactating ruminally cannulated Holstein cows. Feeds were
      incubated in the rumen for 3, 6, 12, 18, 24, and 36 h. Intestinal CP
      digestibility via pepsin and pancreatin and AA profiles were measured on residue
      from 12-h ruminal incubation of feeds. Ruminal undegradable protein (RUP) was
      less for SBM (46.4%) than for DG. The WDG (53.6%) had less RUP than dried DG. The
      RUP concentrations of DG3 (59.1%) and DG5 (60.3%) were lower than DG1 (71.7%) and
      DG4 (67.5%), with DG1 having more than DG2 (63.7%) and DG4. Intestinal
      digestibility of RUP was greater for SBM (86.7%) than DG. The DG2 (76.8%) and DG3
      (74.2%) had greater intestinal digestibility compared with DG1 (59.2%), DG4
      (63.0%), and DG5 (68.1%). The intestinal digestibility in WDG (65.8%) was similar
      to all other DG except for DG1, which was lower. Total digestibility of CP was
      greater in SBM (93.9%) compared with DG. Among the DG sources, the CP in DG2
      (85.3%) and DG3 (84.9%) was more digestible compared with DG1 (70.7%), DG4
      (74.9%), and DG5 (80.8%) but not WDG (81.9%). Based on the milk protein score
      (MPS), which is an estimate of the proportion of milk protein that a protein
      source can sustain until the first limiting AA is depleted, Met was the first
      limiting AA in SBM and Lys in DG. The concentrations of essential AA in the RUP
      were not different among DG sources, but the greater MPS in WDG (0.306) compared
      with the dried DG (0.240) sources indicated that WDG may have been the more ideal
      RUP source; but, the MPS of the metabolizable protein indicated that the protein
      quality of WDG was similar to that in DG2, DG3, and DG5. In conclusion, protein
      degradability and digestibility differed greatly among DG sources, but these
      differences were actually not as prominent in the concentrations of metabolizable
      AA and MPS among these sources.

PMID- 17517732
TI  - Cheese manufacture with milk with elevated conjugated linoleic acid levels caused
      by dietary manipulation.
AB  - The objective of this study was to assess the effect of dietary supplementation
      of cows on pasture with sunflower oil for conjugated linoleic acid (cis-9, trans
      11 CLA) enrichment of milk, for the production of CLA-enriched cheese. A group of
      40 autumn-calving dairy cows were assigned to either a control group (indoor
      feeding on grass silage ad libitum and 6 kg/d of a typical indoor concentrate) or
      an experimental group (on pasture, being fed 6 kg of a supplement containing 100
      g/kg of sunflower oil per d). These diets were fed for 16 d, during which time
      milk was collected for pilot-scale hard cheese manufacture. The pasture-based
      diet with sunflower oil resulted in a significant effect on the milk fatty acid
      CLA content. The concentration of cis-9, trans-11 CLA in the milk produced from
      cows on this diet increased to 2.22 g/100 g of fatty acid methyl esters (FAME)
      after 14 d, compared with 0.46 g/100 g of FAME in milk produced on the control
      indoor diet. The content of cis-9, trans-11 CLA in the cheese manufactured from
      the indoor control milk was 0.78 g/100 g of FAME and that from the pasture-based
      sunflower oil milk was 1.93 g/100 g of FAME. The cheese was assessed during the
      ripening period and CLA concentrations were stable throughout the 6 mo of
      ripening. Other cheese variables (microbiology, composition, flavor, free AA)
      were monitored during the ripening period, and the cheese with the elevated CLA
      concentrations compared favorably with the control cheese. Thus, a pasture-based
      diet supplemented with an oil source rich in linoleic acid resulted in an
      enhanced CLA content of bovine milk fat, compared with an indoor grass silage
      based diet.

PMID- 17517733
TI  - Production performance and milk composition of dairy cows fed whole or ground
      flaxseed with or without monensin.
AB  - Eight multiparous Holstein cows averaging 570 +/- 43 kg of body weight and 60 +/-
      20 d in milk were used in a double Latin square design with four 21-d
      experimental periods to determine the effects of feeding ground or whole flaxseed
      with or without monensin supplementation (0.02% on a dry matter basis) on milk
      production and composition, feed intake, digestion, blood composition, and fatty
      acid profile of milk. Intake of dry matter was similar among treatments. Cows fed
      whole flaxseed had higher digestibility of acid detergent fiber but lower
      digestibilities of crude protein and ether extract than those fed ground
      flaxseed; monensin had no effect on digestibility. Milk production tended to be
      greater for cows fed ground flaxseed (22.8 kg/d) compared with those fed whole
      flaxseed (21.4 kg/d). Processing of flax-seed had no effect on 4% fat-corrected
      milk yield and milk protein and lactose concentrations. Monensin supplementation
      had no effect on milk production but decreased 4% fat-corrected milk yield as a
      result of a decrease in milk fat concentration. Feeding ground compared with
      whole flaxseed decreased concentrations of 16:0, 17:0, and cis6-20:4 and
      increased those of cis6-18:2, cis9, trans11-18:2, and cis3-18:3 in milk fat. As a
      result, there was a decrease in concentrations of medium-chain and saturated
      fatty acids and a trend for higher concentrations of long-chain fatty acids in
      milk fat when feeding ground compared with whole flaxseed. Monensin
      supplementation increased concentrations of cis9 and trans11-18:2 and decreased
      concentrations of saturated fatty acids in milk fat. There was an interaction
      between flaxseed processing and monensin supplementation, with higher milk fat
      concentration of trans11-18:1 for cows fed ground flaxseed with monensin than for
      those fed the other diets. Flaxseed processing and monensin supplementation
      successfully modified the fatty acid composition of milk fat that might favor
      nutritional value for consumers.

PMID- 17517734
TI  - Short communication: Absorption of 2-hydroxy-4-methylthiobutanoate in dairy cows.
AB  - The objective of this study was to measure net portal absorption of 2-hydroxy-4
      methylthiobutanoate (HMTBA) in dairy cows. Four multicatheterized lactating cows
      were used in a cross-over design with 7-d experimental periods. They were fed
      every other hour a total mixed ration and received, in addition, twice a day,
      12.5 or 25 g/meal of HMTBA. On the last day of treatment, net portal absorption
      of HMTBA was numerically greater after the 25-g compared with the 12.5-g bolus
      meal of HMTBA, and the amount absorbed relative to the dose ingested was
      unchanged between treatments averaging 11.2 +/- 4.7% of the dose. This represents
      a minimum value of HMTBA availability because it does not take into account any
      HMTBA metabolized to Met by gut tissues (in sheep this amounted to another 5% of
      the dose). A rapid method to estimate net portal absorption based on temporal
      variations of the peripheral plasma HMTBA concentrations following the HMTBA meal
      is also presented. Based on the good relationship (concordance correlation
      coefficient = 0.97) observed between direct measurements and estimations, this
      simplified approach offers a reasonable approach to assess HMTBA absorption under
      different feeding situations.

PMID- 17517735
TI  - Prepartum nutrition alters fatty acid composition in plasma, adipose tissue, and
      liver lipids of periparturient dairy cows.
AB  - The fatty acyl profile of phospholipids (PL) determines the fluidity of cell
      membranes and affects cell function. The degree to which long-chain fatty acid
      (LCFA) composition of PL and triacylglycerols (TG) in liver and total lipids in
      adipose tissue can be altered by prepartum nutrition in peripartal dairy cows is
      unclear. Multiparous Holsteins (n = 25) were assigned to 1 of 4 prepartal diets:
      1) CA, the control diet fed to meet 120% of energy requirements; 2) CR, a control
      diet fed to meet 80% of requirements; 3) S, a diet supplemented with mostly
      saturated free fatty acids (47% 16:0, 36% 18:0, 14% cis-18:1) and fed to meet
      120% of requirements; or 4) U, a diet similar to S except that cows were
      abomasally infused with soybean oil so that the diet plus infused fat would meet
      120% of requirements. Diets were fed for 40 d prepartum; all cows received a
      lactation diet postpartum. Groups CR and U had lower prepartum intakes of dry
      matter and net energy, but glucose concentrations in plasma were similar among
      treatments. Cows fed S, U, or CR had greater nonesterified fatty acids in plasma
      prepartum, but cows fed U had decreased beta-hydroxybutyrate postpartum.
      Postpartal concentrations of total lipids and glycogen in liver tissue were
      similar among treatments. Cows in group U had a greater percentage of 18:2 but
      less 16:0, 18:0, and 20:4 in plasma total lipids than cows fed S. Treatment U
      increased 18:2 and 18:3 and decreased 18:1 in subcutaneous adipose tissue at 1 d
      postpartum. Across diets, percentages of 16:0 and trans-18:1 were increased, and
      18:0, 20:3, and 20:5 were decreased, in hepatic PL at d 1 postpartum. Significant
      treatment x time interactions indicated that treatment U increased 18:2 in
      hepatic PL at the expense of 18:1, 20:3, 20:4, 22:6, and 24:0 on d 1 postpartum,
      but changes were normalized by d 65 postpartum. The unsaturation index of hepatic
      PL was lower at d 1 than at d -45 or 65, which implies that hepatic membrane
      fluidity decreased around parturition. The unsaturation index at d 1 was greater
      for cows fed S than those fed CA or U. Percentages of 16:0, 18:1, and 22:0 were
      increased, and 18:0, 20:3, 20:4, 20:5, 24:0, and 26:0 were decreased, in hepatic
      TG at d 1. Prepartal feed restriction modestly affected tissue LCFA profiles. The
      LCFA profile of adipose tissue, liver PL, and liver TG can be altered by dietary
      LCFA supply prepartum; changes in liver are normalized by 65 d postpartum.

PMID- 17517736
TI  - Effect of level of metabolizable protein on milk production and nitrogen
      utilization in lactating dairy cows.
AB  - The objective of this study was to investigate the effects of the level of
      metabolizable protein (MP) on milk production and nitrogen utilization in Chinese
      Holstein dairy cows. Forty multiparous dairy cows (body weight = 590 kg; days in
      milk = 135; average milk yield = 30.2 kg/d) were assigned to treatments randomly
      within groups based on days in milk and milk production. Animals were offered
      diets with different levels of MP: 8.3% (diet A), 8.9% (diet B), 9.7% (diet C),
      and 10.4% (diet D) of dry matter. The MP level in diet A was designed to meet the
      current Chinese National Station of Animal Production and Health guidelines,
      whereas that in diet D was based on the National Research Council (2001) model.
      The experiment lasted for 7 wk. Milk yield and milk composition (fat, protein,
      and lactose) were recorded, and urea nitrogen concentrations in serum, urine, and
      milk were measured during the experiment. Milk yield and milk protein percentage
      increased as the MP increased up to 9.7% of dry matter, and then leveled off.
      Concentrations of nitrogen in urine, serum, and milk increased linearly as the
      amount of MP was increased, indicating decreased efficiency of nitrogen
      utilization. Milk lactose percentage and total solids percentage showed no
      significant differences among the 4 diets. We concluded that the optimal dietary
      MP level was at 9.6% of dry matter for Chinese Holstein dairy cows producing 30
      kg of milk per day.

PMID- 17517737
TI  - The association of bovine PPARGC1A and OPN genes with milk composition in two
      independent Holstein cattle populations.
AB  - Many studies have reported quantitative trait loci on chromosome 6 that affect
      milk production traits in dairy cattle. Osteopontin (OPN) and peroxisome
      proliferator activated receptor gamma coactivator 1 alpha (PPARGC1A) are located
      in the middle of chromosome 6 about 6 Mb apart, which is approximately 12 cM. The
      objective of this study was to investigate the association of OPN and PPARGC1A
      variants with milk production traits in 2 independent Holstein cattle
      populations: the University of Wisconsin (UW) daughter design and the Cooperative
      Dairy DNA Repository (CDDR) granddaughter design resource populations. For OPN,
      891 cows from the UW resource population were genotyped for the C/T polymorphism
      reported previously in the CDDR population. Additive effects were significant for
      fat percentage, protein percentage, and fat yield in the UW resource population.
      These results are consistent with previous studies that have shown significant
      association of OPN variants with milk composition traits. The association between
      PPARC1A variants was investigated in UW and CDDR resource populations using 2
      single nucleotide polymorphisms. For the UW resource population, additive effects
      were significantly increased for protein percentage and decreased for milk yield.
      Dominance effects were not significant for any of the examined traits. For the
      CDDR population, PPARGC1A was associated with a significant increase in milk
      protein percentage and in SCS. Thus, in UW and CDDR populations, PPARGC1A was
      associated with a significant increase in milk protein percentage in contrast to
      association results previously reported for the German Holstein population.

PMID- 17517738
TI  - Statistical modeling of candidate gene effects on milk production traits in dairy
      cattle.
AB  - A major objective of dairy cattle genomic research is to identify genes
      underlying the variability of milk production traits that could be useful in
      breeding programs. The candidate gene approach provides tools for searching for
      causative polymorphisms affecting quantitative traits. Genes with a possible
      effect on milk traits in cattle can be involved in different physiological
      pathways, such as triglyceride synthesis [acyl-CoA:diacylglycerol acyltransferase
      1 gene (DGAT1)], fat secretion from the mammary epithelial tissue (butyrophilin),
      or entire-body energy homeostasis regulation (leptin and leptin receptor). In
      this study, based on data from 252 Black and White bulls from the active Polish
      dairy population, effects and potential interactions of 9 single nucleotide
      polymorphisms in the butyrophilin, DGAT1, leptin, and leptin receptor genes were
      investigated. Additionally, the effect of the number of additive, dominance, and
      epistatic genetic effects fitted into the model on the estimates of model
      parameters and model selection was illustrated. Phenotypic records were daughter
      yield deviations for milk, fat, and protein yields, obtained from a routine
      national genetic evaluation. Out of all the analyzed polymorphisms, DGAT1 K232A
      had a much larger effect on milk traits than the other single nucleotide
      polymorphisms considered. Estimates of the additive genetic effect of K232A
      expressed as half of the difference between Lys- and Ala-encoding variants were 
      107.4 kg of milk, 5.4 kg of fat, and -1.6 kg of protein at first parity, as well
      as -120 kg of milk and 6.8 kg of fat at second parity. In terms of model
      selection, it was demonstrated that the modified version of Bayesian information
      criterion selects models with the parameterization reflecting the genetic
      background of the analyzed trait, while the Bayesian information criterion
      chooses models that are too highly parameterized.

PMID- 17517739
TI  - Characterization of the DGAT1 K232A and variable number of tandem repeat
      polymorphisms in French dairy cattle.
AB  - A quantitative trait locus (QTL) underlying different milk production traits has
      been identified with a high significance threshold value in the genomic region
      containing the acylCoA:diacylglycerol acyltransferase (DGAT1) gene, in the 3 main
      French dairy cattle breeds: French Holstein, Normande, and Montbeliarde. Previous
      studies have confirmed that the K232A polymorphism in DGAT1 is responsible for a
      major QTL underlying several milk production traits in Holstein dairy cattle and
      several other bovine breeds. In this study, we estimate the frequency of the 2
      alternative alleles, K and A, of the K232A polymorphism in French Holstein,
      Normande, and Montbeliarde breeds. Although the K allele segregates in French
      Holstein and Normande breeds with a similar effect on production traits, the
      existence of additional mutations contributing to the observed QTL effect is
      strongly suggested in both breeds by the existence of sires heterozygous at the
      QTL but homozygous at the K232A polymorphism. One allele at a variable number of
      tandem repeats (VNTR) locus in the 5' noncoding region of DGAT1 has been recently
      proposed as a putative causative variant. In our study, this marker was found to
      present a high mutation rate of 0.8% per gamete and per generation, making the
      allele diversity observed compatible with that expected under neutrality.
      Moreover, among the sires homozygous at the K232A polymorphism, no allele at the
      VNTR can fully explain their QTL status. Finally, no allele at the VNTR was found
      to be significantly associated with the fat percentage variation in the 3 breeds
      simultaneously after correction for the effect of the K232A polymorphism.
      Therefore, our results suggest the existence of at least one other causative
      polymorphism not yet described. Because the A allele is nearly fixed in the
      Montbeliarde breed, this breed represents an interesting model to identify and
      confirm other mutations that have a strong effect on milk production traits.

PMID- 17517740
TI  - Characterization of the casein gene complex in West African goats and description
      of a new alpha(s1)-casein polymorphism.
AB  - The analysis of casein polymorphisms was carried out in West Africa goat
      populations: Red Sokoto (n = 57), West African Dwarf Nigeria (n = 27), West
      African Dwarf Cameroon (n = 39), and Borno (n = 37). The 4 casein genes alpha(s1)
      (CSN1S1), beta (CSN2), alpha(s2) (CSN1S2), and kappa (CSN3) were typed at the DNA
      level. No null alleles were found in any of the genes analyzed. A PCR single
      strand conformation polymorphism method was implemented for the identification of
      CSN1S1*F allele simultaneously with A/0(1), B/E, N and the new allele. The allele
      differed from CSN1S1*B by a synonymous transversion TCG-->TCT in the codon
      corresponding to Ser(66) of the mature protein. The new allele, named CSN1S1*B',
      occurred at a high frequency in all the populations, ranging from 0.295 (West
      African Dwarf Cameroon) to 0.405 (Borno). A greater frequency was found for
      alleles associated with high alpha(s1)-casein quantity, as has already been
      observed in the goat populations from the Mediterranean area. The intermediate E
      allele occurred only in the Red Sokoto and at a low frequency. The faint F allele
      occurred in 3 populations at frequencies lower than 0.03. Linkage disequilibrium
      occurred in all the populations, with highly significant differences in Borno,
      Red Sokoto, and West Africa Dwarf Nigeria, and significant differences in West
      Africa Dwarf Cameroon. Only 10 haplotypes showed frequencies > or =0.05 in at
      least 1 of the 4 populations considered, and the overall frequency was >0.1 only
      for 4 haplotypes: BAAB, B'ACA, ACAB, and BACA (in the order CSN1S1-CSN2-CSN1S2
      CSN3). Haplotype BAAB, postulated as an ancestral haplotype in previous studies,
      was the most common haplotype in all breeds except Borno, where B'ACA was
      predominant. The results obtained are of considerable significance given that
      very little information exists on the subject for African goats. The high
      frequency of strong alleles in the calcium-sensitive caseins as well as the high
      linkage disequilibrium found among the casein genes in the African breeds
      analyzed may suggest that specific casein haplotypes have already been selected
      due to their advantages for nutrition. Haplotypes providing greater protein and
      casein content would increase the energy content of milk, thus resulting in more
      favorable growth and survival of young goats and humans consuming the milk.

PMID- 17517741
TI  - Characterization of genetic polymorphism of the bovine lymphocyte antigen DRB3.2
      locus in Kankrej cattle (Bos indicus).
AB  - Bovine lymphocyte antigen DRB 3.2 (BoLA-DRB3.2) gene encodes for the beta chain
      of the major histocompatibility complex (MHC) class II molecule in cattle, which
      is a glycoprotein present on the surface of antigen-presenting cells. This locus
      shows extensive polymorphism in it. The objective of the present study was to
      genotype the BoLA-DRB3.2 locus in Kankrej cattle (n = 50) by PCR-RFLP. Bovine DNA
      was isolated from aliquots of whole blood. Primers specific for exon 2 of the
      bovine lymphocyte antigen (BoLA)-DRB3 gene were used to amplify the region. The
      304-bp amplified product of the DRB3 gene was separately digested with
      restriction endonucleases RsaI, BstYI, and Hae III. Twenty-four BoLA-DRB 3.2
      alleles were identified with frequencies ranging from 1 to 22.0%. Twenty-one
      alleles of the total 24 alleles were similar to those reported earlier; 3 alleles
      were new and had not been reported previously. The allele BoLA-DRB3.2*34 occurred
      at the highest frequency of 22% (approx.) in the Kankrej animals studied. Six
      alleles (BoLA-DRB3.2 *34, *15, *06, *20, *37, and *20) accounted for almost 71%
      of the total alleles observed to be present in the Kankrej animals. All the new
      alleles observed were present at frequencies of 1%. The results obtained in the
      present study demonstrated that the BoLA DRB3.2 locus is highly polymorphic in
      the Kankrej cattle.

PMID- 17517742
TI  - A stochastic simulation study on validation of an approximate multitrait model
      using preadjusted data for prediction of breeding values.
AB  - Three different models for prediction of breeding values were compared in a
      stochastic simulation study of a dairy cattle population of 100,000 cows. The
      simulation was done in 2 steps. The first step involved 15 yr of selection using
      breeding values obtained in a univariate model for production and a trivariate
      model for mastitis occurrence, udder depth, and somatic cell score, in which
      production and mastitis occurrence were included in the breeding goal. This was
      done to create an initial population that had already been under selection. The
      second step consisted of 20 replicates of 4 different scenarios set up to make it
      possible to compare the different models. Two scenarios were based on univariate
      evaluations and one for udder health traits on trivariate evaluations, with 2
      different breeding goals. In another scenario, an approximate multitrait model
      using preadjusted data in a 2-step procedure was used and in the last scenario, a
      complete linear multitrait model was carried out. Differences in genetic response
      in total merit over the last 15 yr of selection were compared and used to rank
      the models. The linear multitrait model gave the highest regression coefficient
      of true genetic values on year (3.073 +/- 0.069 in economic units), and this was
      significantly better than for the approximate multitrait model (2.819 +/- 0.047),
      which again was significantly better than for the univariate approach (2.672 +/-
      0.060). The linear multitrait model cannot be applied to nearly the same number
      of traits as the approximate model. Therefore, the approximate model with
      developments handling breeding values from more complex models than presented in
      this paper is an option of choice in countries providing total merit indices that
      combine many traits because it does not neglect correlations between these
      traits.

PMID- 17517743
TI  - Short communication: Identification of two polymorphisms in the goat lipoprotein
      lipase gene and their association with milk production traits.
AB  - Lipoprotein lipase (LPL) is a glycoprotein that plays a central role in plasma
      triglyceride metabolism by hydrolyzing triglyceride-rich chylomicrons and very
      low density lipoproteins. The activity of milk LPL has been shown to differ among
      several goat breeds, suggesting the existence of a genetic polymorphism
      influencing the functional properties of this enzyme. We have characterized the
      complete coding sequence of the goat LPL gene in 18 individuals belonging to 3
      breeds. The coding region of the goat LPL cDNA was 1,437 bp long and encoded a
      protein of 478 amino acids. Moreover, we have identified 2 single nucleotide
      polymorphisms (SNP) including a G50C missense mutation, which involved a Ser-
      >Thr amino acid replacement at position 17 of the signal peptide, and a C2094T
      substitution in the 3' untranslated region. A univariate mixed model was used to
      evaluate the association between LPL genotypes and milk production and
      composition in 130 Murciano-Granadina goats. The G50C SNP was suggestively
      associated with milk fat content and tended to affect the milk dry weight basis.
      The C2094T SNP was not associated with any of the measured traits.

PMID- 17517744
TI  - Evaluation of chemical parameters in soft mold-ripened cheese during ripening by
      mid-infrared spectroscopy.
AB  - The suitability of mid-infrared spectroscopy (MIR) to follow the evolution
      throughout ripening of specific physicochemical parameters in Camembert-type
      cheeses was evaluated. The infrared spectra were obtained directly from raw
      cheese samples deposited on an attenuated total reflectance crystal. Significant
      correlations were observed between physicochemical data, pH, acid-soluble
      nitrogen, nonprotein nitrogen, ammonia (NH4+), lactose, and lactic acid. Dry
      matter showed significant correlation only with lactose and nonprotein nitrogen.
      Principal components analysis factorial maps of physicochemical data showed a
      ripening evolution in 2 steps, from d 1 to d 7 and from d 8 to d 27, similar to
      that observed previously from infrared spectral data. Partial least squares
      regressions made it possible to obtain good prediction models for dry matter,
      acid-soluble nitrogen, nonprotein nitrogen, lactose, lactic acid, and NH4+ values
      from spectral data of raw cheese. The values of 3 statistical parameters
      (coefficient of determination, root mean square error of cross validation, and
      ratio prediction deviation) are satisfactory. Less precise models were obtained
      for pH.

PMID- 17517745
TI  - Effects of physical form of a starter for dairy replacement calves on feed intake
      and performance.
AB  - One hundred six female Holstein calves [body weight (BW) = 41.5 +/- 0.37 kg and
      11.2 +/- 0.3 d old] were used to evaluate the effects of physical form of a
      starter on animal performance and starter intake. Calves were randomly allocated
      to 2 treatments consisting of either a multiparticle or a pelleted starter. Both
      starters had exactly the same ingredient and nutrient composition but differed in
      their physical form. Calves received 4 L/d of the same milk replacer at a 150
      g/kg dilution rate in 2 offers of 2 L each until they consumed an average of 300
      g/d of starter (as fed) for 2 consecutive days; then the dilution rate was
      decreased to 120 g/kg until the age of 49 d when milk replacer was limited to 1
      daily dose of 2 L until 57 d of age. Calves were kept in individual hutches for
      at least 1 wk after weaning. Body weight was measured at the beginning of the
      study and at 49 and 64 d of age. The median perimeters for the multiparticle and
      pelleted starters were 0.61 +/- 0.016 and 2.71 +/- 0.082 cm, respectively.
      Overall starter consumption was greater in calves receiving the multiparticle
      starter (944.8 +/- 30.01 g/d) than in those receiving the pelleted starter (863.9
      +/- 32.04 g/d). There were no differences in the total milk replacer intake
      between the 2 treatments. Calf BW when leaving the individual hutches at the end
      of the study was similar between both treatments. Consequently, feed conversion
      efficiency was greater in calves consuming the pelleted than the multiparticle
      starter up to 64 d of age, mainly due to the greater conversion efficiency
      obtained with the pelleted than with the multiparticle starter after the
      preweaning period. It is concluded that pelleted starters may result in lower dry
      feed consumption compared with multiparticle starters, but because final BW was
      similar in both treatments, feed efficiency of calves consuming pelleted starters
      may be greater than that of calves consuming multiparticle starters. Therefore,
      when feeding a starter with similar nutrient composition to the one used in this
      study, there seems to be an economic advantage associated with feeding the
      starter in a pelleted form compared with a multiparticle form.

PMID- 17517746
TI  - Efficiency of use of imported magnesium, sulfur, copper, and zinc on Idaho dairy
      farms.
AB  - Six commercial dairies from south central Idaho were surveyed to estimate the
      whole-farm surpluses of magnesium (Mg), sulfur (S), copper (Cu), and zinc (Zn).
      Mineral imports and exports were monitored in a 12-mo period and samples from the
      diets, feeds, feces, urine, and manure were collected at regular farm visits.
      Soils from manure-amended fields were sampled in the spring and fall. In all
      cases, the largest import of Mg, S, Cu, and Zn to the dairy was with purchased
      feeds, from 91 (S) to 97% (Zn) of all imports. The major mineral export item was
      manure [from 60% (S) to 89% (Cu) of all exports] and forages, in the case of a
      dairy with a large land base. Export with milk represented on average only 8.6,
      25, 2.1, and 11% (Mg, S, Cu, and Zn, respectively) of all exports. Thus, the
      conversion of the imported feed Mg, S, Cu, and Zn into milk was rather low (on a
      whole-farm scale): 5.6, 11, 1.4, and 5.2%, respectively. Concentrations of Mg,
      Cu, and Zn in the lactating cow diets from the participating dairies exceeded
      National Research Council (2001) recommendations on average by 85, 34, and 73%,
      respectively, which contributed to the inefficient use of imported minerals.
      Whole-farm Mg surplus varied from 4 to 54 t/yr (3 to 19 kg/cow per year). The
      efficiency of use of imported Mg varied from 27 to 88%. Sulfur surpluses were
      from 9 to 52 t/yr (12 to 40 kg/cow per year). Copper and Zn surpluses were also
      significant (average of 59 and 585 kg/yr and 0.05 and 0.4 kg/cow per year,
      respectively). The average efficiency of use of imported S, Cu, and Mg was 44,
      62, and 56%, respectively and, as with Mg, varied significantly among the
      dairies. The results from this study suggest that reduction in the concentration
      of dietary Mg, Cu, and Zn is potentially the most efficient way of reducing
      overall excretions and whole-farm surpluses of these minerals.

PMID- 17517747
TI  - Optimal choice of dairy forages in eastern Australia.
AB  - Although several forage species such as perennial ryegrass are predominant, there
      is a wide range of forage species that could be grown in subtropical and
      temperate regions in Australia as dairy pastures. These species have differing
      seasonal patterns of growth, nutrient quality, and water-use efficiency, as
      demonstrated in a large experiment evaluating over 30 species at the University
      of Sydney (Camden, New South Wales, Australia). Some species can be grazed,
      whereas others require mechanical harvesting, which incurs a further cost.
      Previous comparisons of species that relied on yield of dry matter per unit of
      some input (typically land or water) did not simultaneously take into account the
      season in which forage is produced, or other factors related to the costs of
      production and delivery to the cows. To effectively compare the profitability of
      individual species, or combinations of species, requires the use of a whole-farm,
      multiperiod model. Linear programming was used to find the most profitable mix of
      forage species for an irrigated dairy farm in a warm temperate irrigation region
      of New South Wales, Australia. It was concluded that for a typical farmer facing
      the prevailing milk and purchased feed prices with average milk production per
      cow, the most profitable mix of species would include a large proportion of
      perennial ryegrass (Lolium perenne) and prairie grass (Bromus willdenowii). The
      result was robust to changes in seasonal milk pricing and a move from year-round
      to a more seasonal calving pattern.

PMID- 17517748
TI  - The effect of early-lactation feeding strategy on the lactation performance of
      spring-calving dairy cows.
AB  - The objective of this study was to establish the influence of daily herbage
      allowance (DHA) and supplementation level offered to spring-calving dairy cows in
      early lactation on animal performance throughout lactation. Sixty-six Holstein
      Friesian dairy cows were randomly assigned to a 6-treatment grazing study. The
      treatments comprised 3 DHA levels (13, 16, and 19 kg of DM/cow; >4 cm) and 2
      concentrate supplementation levels (0 and 4 kg of DM/cow per day). Treatments
      were imposed from February 21 to May 8 (period 1; P1). During the subsequent 4-wk
      (period 2; P2), animals were offered a DHA of 20 kg of DM/cow and no concentrate.
      Subsequently, all animals grazed as a single herd to the end of lactation. Sward
      quality was homogeneous throughout lactation. A low DHA increased sward
      utilization (+14%) but reduced milk, solids-corrected milk, protein, and lactose
      yields compared with a high DHA during P1. Concentrate supplementation
      significantly increased milk, solids-corrected milk, fat, protein, and lactose
      yields during P1. The positive effect of concentrate supplementation remained
      throughout P2. A total concentrate input of 380 kg of DM/cow increased total
      lactation milk (+432 kg), solids-corrected milk (+416 kg), fat (+18 kg), protein
      (+15 kg), and lactose (+23 kg) yields. Greater P1 body weights were recorded when
      a high DHA and concentrate were offered. The P1 treatment had no effect on body
      condition score throughout lactation. The results indicate that offering a low
      DHA in early spring does not adversely affect total milk production, body weight,
      or body condition score, and offering concentrate results in a greater total
      lactation milk production performance.

PMID- 17517749
TI  - Ruminal nitrogen metabolism: perspectives for integration of microbiology and
      nutrition for dairy.
AB  - Our objectives are to integrate current knowledge with a future perspective
      regarding how metagenomics can be used to integrate rumen microbiology and
      nutrition. Ruminal NH3-N concentration is a crude predictor of efficiency of
      dietary N conversion into microbial N, but as this concentration decreases below
      approximately 5 mg/dL (the value most often suggested to be the requirement for
      optimal microbial protein synthesis), blood urea N transfer into the rumen
      provides an increasing buffer against excessively low NH3-N concentrations, and
      the supply of amino N might become increasingly important to improve microbial
      function in dairy diets. Defaunation typically decreases NH3-N concentration,
      which should increase the efficiency of blood urea N and protein-derived NH3-N
      conversion into microbial protein in the rumen. Thus, we explain why more
      emphasis should be given toward characterization of protozoal interactions with
      proteolytic and deaminating bacterial populations. In contrast with research
      evaluating effects of protozoa on N metabolism, which has primarily been done
      with sheep and cattle with low dry matter intake, dairy cattle have greater
      intakes of readily available carbohydrate combined with increased ruminal passage
      rates. We argue that these conditions decrease protozoal biomass relative to
      bacterial biomass and increase the efficiency of protozoal growth, thus reducing
      the negative effects of bacterial predation compared with the beneficial effects
      that protozoa have on stabilizing the entire microbial ecosystem. A better
      understanding of mechanistic processes altering the production and uptake of
      amino N will help us to improve the overall conversion of dietary N into
      microbial protein and provide key information needed to further improve
      mechanistic models describing rumen function and evaluating dietary conditions
      that influence the efficiency of conversion of dietary N into milk protein.

PMID- 17517750
TI  - Ruminal acidosis in beef cattle: the current microbiological and nutritional
      outlook.
AB  - Ruminal acidosis continues to be a common ruminal digestive disorder in beef
      cattle and can lead to marked reductions in cattle performance. Ruminal acidosis
      or increased accumulation of organic acids in the rumen reflects imbalance
      between microbial production, microbial utilization, and ruminal absorption of
      organic acids. The severity of acidosis, generally related to the amount,
      frequency, and duration of grain feeding, varies from acute acidosis due to
      lactic acid accumulation, to subacute acidosis due to accumulation of volatile
      fatty acids in the rumen. Ruminal microbial changes associated with acidosis are
      reflective of increased availability of fermentable substrates and subsequent
      accumulation of organic acids. Microbial changes in the rumen associated with
      acute acidosis have been well documented. Microbial changes in subacute acidosis
      resemble those observed during adaptation to grain feeding and have not been well
      documented. The decrease in ciliated protozoal population is a common feature of
      both forms of acidosis and may be a good microbial indicator of an acidotic
      rumen. Other microbial factors, such as endotoxin and histamine, are thought to
      contribute to the systemic effects of acidosis. Various models have been
      developed to assess the effects of variation in feed intake, dietary roughage
      amount and source, dietary grain amount and processing, step-up regimen, dietary
      addition of fibrous byproducts, and feed additives. Models have been developed to
      study effects of management considerations on acidosis in cattle previously
      adapted to grain-based diets. Although these models have provided useful
      information related to ruminal acidosis, many are inadequate for detecting
      responses to treatment due to inadequate replication, low feed intakes by the
      experimental cattle that can limit the expression of acidosis, and the feeding of
      cattle individually, which reduces experimental variation but limits the ability
      of researchers to extrapolate the data to cattle performing at industry
      standards. Optimal model systems for assessing effects of various management and
      nutritional strategies on ruminal acidosis will require technologies that allow
      feed intake patterns, ruminal conditions, and animal health and performance to be
      measured simultaneously in a large number of cattle managed under conditions
      similar to commercial feed yards. Such data could provide valuable insight into
      the true extent to which acidosis affects cattle performance.

PMID- 17517751
TI  - Cumulative physiological events influence the inflammatory response of the bovine
      udder to Escherichia coli infections during the transition period.
AB  - A high proportion of intramammary coliform infections present at parturition
      develop disease characterized by severe inflammatory signs and sepsis during the
      first 60 to 70 d of lactation. In the lactating bovine mammary gland, the innate
      immune system plays a critical role in determining the outcome of these
      infections. Since the beginning of the 1990s, research has increased
      significantly on bovine mammary innate defense mechanisms in connection with the
      pathogenesis of coliform mastitis. Neutrophils are key effector cells of the
      innate immune response to intramammary infection, and their function is
      influenced by many physiological events that occur during the transition period.
      Opportunistic infections occur when the integrity of the host immune system is
      compromised by physical and physiological conditions that make the host more
      susceptible. The innate immune system of many periparturient cows is
      immunocompromised. It is unlikely that periparturient immunosuppression is the
      result of a single physiological factor; more likely, several entities act in
      concert, with profound effects on the function of many organ systems of the
      periparturient dairy cow. Their defense system is unable to modulate the complex
      network of innate immune responses, leading to incomplete resolution of the
      pathogen and the inflammatory reaction. During the last 30 yr, most efforts have
      been focused on neutrophil diapedesis, phagocytosis, and bacterial killing. How
      these functions modulate the clinical outcome of coliform mastitis, and how they
      can be influenced by hormones and metabolism has been the subject of intensive
      research and is the focus of this review. The afferent (sensing) arm of innate
      immunity, which enables host recognition of a diverse array of pathogens, is the
      subject of intense research interest and may contribute to the variable
      inflammatory response to intramammary infections during different stages of
      lactation. The development of novel interventions that modulate the inflammatory
      response or contribute to the elimination of the pathogen or both may offer
      therapeutic promise in the treatment of mastitis in periparturient cows.

PMID- 17517752
TI  - Regulation of gene expression in the bovine mammary gland by ovarian steroids.
AB  - It is well established that estrogen is required for mammary epithelial cell
      proliferation and ductal development in the growing animal, and that
      lobuloalveolar development during gestation is dependent on progesterone. The
      effects of these steroid hormones on gene expression in the mammary gland are
      mediated primarily by their respective nuclear hormone receptors, which function
      as hormone-bound transcription factors. To gain insight into how estrogen and
      progesterone regulate mammary gland growth and function in cattle, we and others
      have characterized the expression patterns of their cognate nuclear hormone
      receptors in the bovine mammary gland throughout development, pregnancy, and
      lactation. This work has identified a lack of expression of estrogen receptor
      beta and a greater abundance of progesterone receptor during lactation in the
      bovine mammary gland, compared with the rodent gland. We speculate that
      interactions among the estrogen receptor isoforms that regulate progesterone
      receptor expression may contribute to these species differences. Further,
      demonstrated expression of substantial quantities of estrogen receptor within the
      prepubertal bovine mammary fat pad, along with coordinated insulin-like growth
      factor-I expression, suggests that this tissue may stimulate parenchymal growth
      via an estrogen-responsive paracrine mechanism. In addition, the recent
      availability of bovine genomic sequence information and microarray technologies
      has permitted the study of global gene expression in the mammary gland in
      response to the steroid environment. We have identified more than 100 estrogen
      responsive genes, of which the majority are novel estrogen gene targets. Estrogen
      induced changes in gene expression were consistent with increased mammary
      epithelial cell proliferation, increased extracellular matrix turnover in
      parenchyma, and increased extracellular matrix deposition in the fat pad. A
      comparison of estrogen-responsive genes in the mammary glands of humans, mice,
      and cattle suggests considerable variation among species, as well as potential
      differences in regulatory elements in common estrogen receptor gene targets.
      Continuing studies using advanced molecular techniques should assist in
      elucidating the complex regulation of mammary function at the transcript level.

PMID- 17517753
TI  - The tammar wallaby and fur seal: models to examine local control of lactation.
AB  - Mammary development and function are regulated by systemic endocrine factors and
      by autocrine mechanisms intrinsic to the mammary gland, both of which act
      concurrently. The composition of milk includes nutritional and developmental
      factors that are crucial to the development of the suckled young, but it is
      becoming increasingly apparent that milk also has a role in regulating mammary
      function. This review examines the option of exploiting the comparative biology
      of species with extreme adaptation to lactation to examine regulatory mechanisms
      that are present but not readily apparent in other laboratory and livestock
      species. The tammar wallaby has adopted a reproductive strategy that includes a
      short gestation (26 d), birth of an immature young, and a relatively long
      lactation (300 d). The composition of milk changes progressively during the
      lactation cycle, and this is controlled by the mother and not the sucking pattern
      of the young. Furthermore, the tammar can practice concurrent asynchronous
      lactation; the mother provides a concentrated milk high in protein and fat for an
      older animal that is out of the pouch and a dilute milk low in fat and protein
      but high in carbohydrates from an adjacent mammary gland for a newborn pouch
      young. This phenomenon suggests that the mammary gland is controlled locally. The
      second study species, the Cape fur seal, has a lactation characterized by a
      repeated cycle of long at-sea foraging trips (up to 28 d) alternating with short
      suckling periods of 2 to 3 d ashore. Lactation almost ceases while the seal is
      off shore, but the mammary gland does not progress to apoptosis and involution,
      most likely because of local control of the mammary gland. Our studies have
      exploited the comparative biology of these models to investigate how mammary
      function is regulated by endocrine factors, and particularly by milk. This review
      reports 3 major findings using these model animals. First, the mammary epithelial
      cell has an extraordinary intrinsic capacity for survival in our culture model,
      and the path to either function or death by apoptosis is actively driven. The
      second outcome is that the route to apoptosis is most likely regulated by
      specific milk factors. Finally, whey acidic protein, a major milk protein in some
      species, may play a role in normal mammary development, but that role in vivo may
      be limited to marsupials. Evolutionary pressure has led to changes in the
      structure of the protein with an accompanying change in function. Therefore, we
      propose that a loss of function of this protein in eutherians may relate to a
      reproductive strategy that is less dependent on lactation.

PMID- 17517754
TI  - Expression and regulation of glucose transporters in the bovine mammary gland.
AB  - Glucose is the primary precursor for the synthesis of lactose, which controls
      milk volume by maintaining the osmolarity of milk. Glucose uptake in the mammary
      gland plays a key role in milk production. Glucose transport across the plasma
      membranes of mammalian cells is carried out by 2 distinct processes: facilitative
      transport, mediated by a family of facilitative glucose transporters (GLUT); and
      sodium-dependent transport, mediated by the Na+/glucose cotransporters (SGLT).
      Transport kinetic studies indicate that glucose transport across the plasma
      membrane of the lactating bovine mammary epithelial cell has a K(m) value of 8.29
      mM for 3-O-methyl-D-glucose and can be inhibited by both cytochalasin-B and
      phloretin, indicating a facilitative transport process. This is consistent with
      the observation that in the lactating bovine mammary gland, GLUT1 is the
      predominant glucose transporter. However, the bovine lactating mammary gland also
      expresses GLUT3, GLUT4, GLUT5, GLUT8, GLUT12, and sodium-dependent SGLT1 and
      SGLT2 at different levels. Studies of protein expression and cellular and
      subcellular localizations of these transporters are needed to address their
      physiological functions in the mammary gland. From late pregnancy to early
      lactation, expression of GLUT1, GLUT8, GLUT12, SGLT1, and SGLT2 mRNA increases
      from at least 5-fold to several hundred-fold, suggesting that these transporters
      may be regulated by lactogenic hormones and have roles in milk synthesis. The
      GLUT1 protein is detected in lactating mammary epithelial cells. Its expression
      level decreases from early to late lactation stages and becomes barely detectable
      in the nonlactating gland. Both GLUT1 mRNA and protein levels in the lactating
      mammary gland are not significantly affected by exogenous bovine growth hormone,
      and, in addition, GLUT1 mRNA does not appear to be affected by leptin.

PMID- 17517755
TI  - Design and analysis of pen studies in the animal sciences.
AB  - Increasingly, research is being performed in which animals subjected to a common
      treatment are also housed in a common pen. Issues have been raised regarding the
      proper planning of experiments and conduct of statistical analyses in these
      instances. This paper reviews the problems associated with ignoring animal
      grouping during data analyses, and examples are provided for appropriate methods
      to use when animals are grouped in pens. Using animals as the error term when
      treatments are applied to pens can result in biased estimates of treatment
      effects when pens are of unequal sizes and animals are moved in and out of the
      pens. It always results in biased probability statements regarding their
      significance. The pen effect includes systematic effects other than that of the
      treatment, which is why pens must be replicated and randomized. In essence, pen
      studies have an implicit split-plot design in which the main plots (pens) receive
      the treatments of interest, whereas the subplots (cows) receive all the same
      subplot treatment. Using the subplot error to test main-plot treatment effects
      creates inflated degrees of freedom and uses the wrong denominator mean square to
      test the effect; hence, severely biasing the test of significance for the
      treatment effects and resulting in an invalid causal inference base. The
      interactions of pens with the fixed-effect elements of the treatment design are
      the correct error terms for those fixed-effects factors applied to the pens. The
      same statistical designs used with animals as experimental units can be used with
      pens. The number of experimental units to achieve a given power can be, and
      generally is, considerably less with pens because the variance among pens is
      generally less than the variance of cows within pens. Pens must be replicated,
      randomized, and included in the statistical model to ensure valid statistical
      inference.

PMID- 17517756
TI  - Do cardiovascular risk factors confer the same risk for cardiovascular outcomes
      in rheumatoid arthritis patients as in non-rheumatoid arthritis patients?
AB  - OBJECTIVE: To compare the frequency of traditional cardiovascular (CV) risk
      factors in rheumatoid arthritis (RA) compared to non-RA subjects, and examine
      their impact on the risk of developing selected CV events (myocardial infarction
      (MI), heart failure (HF) and CV death) in these two groups. METHODS: We examined
      a population-based incidence cohort of subjects with RA (defined according to the
      1987 American College of Rheumatology criteria), and an age- and sex-matched non
      RA cohort. All subjects were followed longitudinally through their complete
      community medical records, until death, migration, or 1 January 2001. Clinical CV
      risk factors and outcomes were defined using validated criteria. The chi2 test
      was used to compare the frequency of each CV risk factor at baseline. Person
      years methods were used to estimate the rate of occurrence of each CV risk factor
      during follow-up. Cox models were used to examine the influence of CV risk
      factors on the development of CV outcomes. RESULTS: A total of 603 RA and 603 non
      RA subjects (73% female; mean age 58 years) were followed for a mean of 15 and 17
      years (total: 8842 and 10,101 person-years), respectively. At baseline, RA
      subjects were significantly more likely to be former or current smokers when
      compared to non-RA subjects (p<0.001). Male gender, smoking, and personal cardiac
      history had weaker associations with CV events among RA subjects, compared to non
      RA subjects. There was no significant difference between RA and non-RA subjects
      in the risk imparted with respect to the other CV risk factors (ie, family
      cardiac history, hypertension, dyslipidaemia, body mass index, or diabetes
      mellitus). CONCLUSION: While some traditional CV risk factors imparted similar
      risk among RA compared with non-RA subjects, others (ie, male gender, smoking and
      personal cardiac history) imparted significantly less risk for the development of
      CV disease. These differences in the overall impact of traditional CV risk
      factors suggest that strategies to prevent CV disease and mortality focused
      solely on controlling traditional CV risk factors may be relatively less
      beneficial in RA subjects than in the general population. Further research is
      needed to determine optimal approaches to reducing CV morbidity and mortality in
      persons with RA.

PMID- 17517758
TI  - Probenazole-induced accumulation of salicylic acid confers resistance to
      Magnaporthe grisea in adult rice plants.
AB  - Probenazole (PBZ) is the active ingredient of Oryzemate, an agrochemical which is
      used for the protection of rice plants from Magnaporthe grisea (blast fungus).
      While PBZ was reported to function upstream of salicylic acid (SA) in
      Arabidopsis, little is known about the mechanism of PBZ-induced resistance in
      rice. The role of SA in blast fungus resistance is also unclear. The recommended
      application period for Oryzemate is just before the Japanese rainy season, at
      which time rice plants in the field have reached the 8-leaf stage with adult
      traits. Thus, the involvement of SA in PBZ-induced resistance was studied in
      compatible and incompatible blast fungus-rice interactions at two developmentally
      different leaf morphology stages. Pre-treatment of inoculated fourth leaves of
      young wild-type rice plants at the 4-leaf stage with PBZ did not influence the
      development of whitish expanding lesions (ELs) in the susceptible interaction
      without the accumulation of SA and pathogenesis-related (PR) proteins. However,
      PBZ pre-treatment increased accumulation of SA and PR proteins in the eighth
      leaves of adult plants at the 8-leaf stage, resulting in the formation of
      hypersensitive reaction (HR) lesions (HRLs). Exogenous SA induced resistance in
      adult but not young plants. SA concentrations in blast fungus-inoculated young
      leaves were essentially the same in compatible and incompatible interactions,
      suggesting that PBZ-induced resistance in rice is age-dependently regulated via
      SA accumulation.

PMID- 17517757
TI  - A closer look at non-Hodgkin's lymphoma cases in a national Swedish systemic
      lupus erythematosus cohort: a nested case-control study.
AB  - OBJECTIVE: To investigate risk factors for non-Hodgkin's lymphoma (NHL) and
      analyse NHL subtypes and characteristics in patients with systemic lupus
      erythematosus (SLE). METHODS: A national SLE cohort identified through SLE
      discharge diagnoses in the Swedish hospital discharge register during 1964 to
      1995 (n = 6438) was linked to the national cancer register. A nested case control
      study on SLE patients who developed NHL during this observation period was
      performed with SLE patients without malignancy as controls. Medical records from
      cases and controls were reviewed. Tissue specimens on which the lymphoma
      diagnosis was based were retrieved and reclassified according to the WHO
      classification. NHLs of the subtype diffuse large B cell lymphoma (DLBCL) were
      subject to additional immunohistochemical staining using antibodies against bcl
      6, CD10 and IRF-4 for further subclassification into germinal centre (GC) or non
      GC subtypes. RESULTS: 16 patients with SLE had NHL, and the DLBCL subtype
      dominated (10 cases). The 5-year overall survival and mean age at NHL diagnosis
      were comparable with NHL in the general population-50% and 61 years,
      respectively. Cyclophosphamide or azathioprine use did not elevate lymphoma risk,
      but the risk was elevated if haematological or sicca symptoms, or pulmonary
      involvement was present in the SLE disease. Two patients had DLBCL-GC subtype and
      an excellent prognosis. CONCLUSIONS: NHL in this national SLE cohort was
      predominated by the aggressive DLBCL subtype. The prognosis of NHL was comparable
      with that of the general lymphoma population. There were no indications of
      treatment-induced lymphomas. Molecular subtyping could be a helpful tool to
      predict prognosis also in SLE patients with DLBCL.

PMID- 17517759
TI  - Litigation against English NHS ambulance services and the rule in Kent v.
      Griffiths.

PMID- 17517760
TI  - Re-detention after recent discharge: a role for judicial review?

PMID- 17517761
TI  - Accuracy of liquid based versus conventional cytology: overall results of new
      technologies for cervical cancer screening: randomised controlled trial.
AB  - OBJECTIVE: To compare the accuracy of conventional cytology with liquid based
      cytology for primary screening of cervical cancer. DESIGN: Randomised controlled
      trial. SETTING: Nine screening programmes in Italy. PARTICIPANTS: Women aged 25
      60 attending for a new screening round: 22 466 were assigned to the conventional
      arm and 22 708 were assigned to the experimental arm. INTERVENTIONS: Conventional
      cytology compared with liquid based cytology and testing for human
      papillomavirus. MAIN OUTCOME MEASURE: Relative sensitivity for cervical
      intraepithelial neoplasia of grade 2 or more at blindly reviewed histology, with
      atypical cells of undetermined significance or more severe cytology considered a
      positive result. RESULTS: In an intention to screen analysis liquid based
      cytology showed no significant increase in sensitivity for cervical
      intraepithelial neoplasia of grade 2 or more (relative sensitivity 1.17, 95%
      confidence interval 0.87 to 1.56) whereas the positive predictive value was
      reduced (relative positive predictive value v conventional cytology 0.58, 0.44 to
      0.77). Liquid based cytology detected more lesions of grade 1 or more (relative
      sensitivity 1.68, 1.40 to 2.02), with a larger increase among women aged 25-34 (P
      for heterogeneity 0.0006), but did not detect more lesions of grade 3 or more
      (relative sensitivity 0.84, 0.56 to 1.25). Results were similar when only low
      grade intraepithelial lesions or more severe cytology were considered a positive
      result. No evidence was found of heterogeneity between centres or of improvement
      with increasing time from start of the study. The relative frequency of women
      with at least one unsatisfactory result was lower with liquid based cytology
      (0.62, 0.56 to 0.69). CONCLUSION: Liquid based cytology showed no statistically
      significant difference in sensitivity to conventional cytology for detection of
      cervical intraepithelial neoplasia of grade 2 or more. More positive results were
      found, however, leading to a lower positive predictive value. A large reduction
      in unsatisfactory smears was evident. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN81678807 [controlled-trials.com].

PMID- 17517762
TI  - INDELSCAN: a web server for comparative identification of species-specific and
      non-species-specific insertion/deletion events.
AB  - Insertion and deletion (indel) events usually have dramatic effects on genome
      structure and gene function. Species-specific indels have been demonstrated to be
      associated with species-unique traits. Currently, indel identifications mainly
      rely on pair-wise sequence alignments (the 'pair-wise indels'), which suffer lack
      of discrimination of species specificity and insertion versus deletion. Also,
      there is no freely accessible web server for genome-wide identification of
      indels. Therefore, we develop a web server--INDELSCAN--to identify four types of
      indels using multiple sequence alignments that include sequences from one target,
      one subject and > or =1 out-group species. The four types of indels identified
      encompass target species-specific, subject species-specific, non-species-specific
      and target-subject pair-wise indels. Insertions and deletions are discriminated
      with reference to out-group sequences. The genomic locations (5'UTR, intron, CDS,
      3'UTR and intergenic region) of these indels are also provided for functional
      analysis. INDELSCAN provides genomic sequences and gene annotations from a wide
      spectrum of taxa for users to select from, including nine target species (human
      (Homo sapiens), mouse (Mus musculus), rat (Rattus norvegicus), dog (Canis
      familiaris), opossum (Monodelphis domestica), chicken (Gallus gallus), zebrafish
      (Danio rerio), fly (Drosophila melanogaster) and yeast (Saccharomyces cerevisiae)
      and >35 subject/out-group species, ranging from yeasts to mammals. The server
      also provides analytic figures and supports indel identification from user
      uploaded alignments/annotations. INDELSCAN is freely accessible at
      http://indelscan.genomics.sinica.edu.tw/IndelScan/.

PMID- 17517763
TI  - 3D-partner: a web server to infer interacting partners and binding models.
AB  - The 3D-partner is a web tool to predict interacting partners and binding models
      of a query protein sequence through structure complexes and a new scoring
      function. 3D-partner first utilizes IMPALA to identify homologous structures
      (templates) of a query from a heterodimer profile library. The interacting
      partner sequence profiles of these templates are then used to search interacting
      candidates of the query from protein sequence databases (e.g. SwissProt) by PSI
      BLAST. We developed a new scoring function, which includes the contact-residue
      interacting score (e.g. the steric, hydrogen bonds, and electrostatic
      interactions) and the template consensus score (e.g. couple-conserved residue and
      the template similarity scores), to evaluate how well the interfaces between the
      query and interacting candidates. Based on this scoring function, 3D-partner
      provides the statistic significance, the binding models (e.g. hydrogen bonds and
      conserved amino acids) and functional annotations of interacting partners. The
      correlation between experimental energies and predicted binding affinities of our
      scoring function is 0.91 on 275 mutated residues from the ASEdb. The average
      precision of the server is 0.72 on 563 queries and the execution time of this
      server for a query is approximately 15 s on average. These results suggest that
      the 3D-partner server can be useful in protein-protein interaction predictions
      and binding model visualizations. The server is available online at: http://3D
      partner.life.nctu.edu.tw.

PMID- 17517764
TI  - M4T: a comparative protein structure modeling server.
AB  - Multiple Mapping Method with Multiple Templates (M4T)
      (http://www.fiserlab.org/servers/m4t) is a fully automated comparative protein
      structure modeling server. The novelty of M4T resides in two of its major
      modules, Multiple Templates (MT) and Multiple Mapping Method (MMM). The MT module
      of M4T selects and optimally combines the sequences of multiple template
      structures through an iterative clustering approach that takes into account the
      'unique' contribution of each template, its sequence similarity to other template
      sequences and to the target sequences, and the quality of its experimental
      resolution. MMM module is a sequence-to-structure alignment method that is aimed
      at improving the alignment accuracy, especially at lower sequence identity
      levels. The current implementation of MMM takes inputs from three profile-to
      profile-based alignment methods and iteratively compares and ranks alternatively
      aligned regions according to their fit in the structural environment of the
      template structure. The performance of M4T was benchmarked on CASP6 comparative
      modeling target sequences and on a larger independent test set and showed a
      favorable performance to current state-of-the-art methods.

PMID- 17517765
TI  - Sp1 and Sp3 regulate basal transcription of the human APOBEC3G gene.
AB  - APOBEC3G (A3G), a member of the recently discovered family of human cytidine
      deaminases, is expressed in peripheral blood lymphocytes and has been shown to be
      active against HIV-1 and other retroviruses. To gain new insights into the
      transcriptional regulation of this restriction factor, we cloned and
      characterized the promoter region of A3G. Transcriptional start sites were
      identified by 5'-rapid amplification of cDNA ends analysis. Luciferase reporter
      assays demonstrated that a 1025 bp A3G promoter sequence (from -959 to +66
      relative to the major transcriptional start site) displayed constitutive promoter
      activity. In T cells, the A3G promoter was not inducible by mitogenic
      stimulation, interferon treatment or expression of HIV-1 proteins. Using a series
      of 5' deletion promoter constructs in luciferase reporter assays, we identified a
      180 bp region that was sufficient for full promoter activity. Transcriptional
      activity of this A3G core promoter was dependent on a GC-box (located at position
      -87/-78 relative to the major transcriptional start site) and was abolished after
      mutation of this DNA element. Electrophoretic mobility shift assays and chromatin
      immunoprecipitation assays demonstrated that the identified GC-box represented a
      binding site for the ubiquitous transcription factors specificity protein (Sp) 1
      and Sp3.

PMID- 17517766
TI  - Three-dimensional model for the isolated recombinant influenza virus polymerase
      heterotrimer.
AB  - The genome of influenza A virus is organized into eight ribonucleoprotein
      complexes (RNPs), each containing one RNA polymerase complex. This RNA polymerase
      has also been found non-associated to RNPs and is possibly involved in distinct
      functions in the infection cycle. We have expressed the virus RNA polymerase
      complex by co-tranfection of the PB1, PB2 and PA genes in mammalian cells and the
      heterotrimer was purified by the TAP tag procedure. Its 3D structure was
      determined by electron microscopy and single-particle image processing. The model
      obtained resembles the structure previously reported for the polymerase complex
      associated to viral RNPs but appears to be in a more open conformation. Detailed
      model comparison indicated that specific areas of the complex show important
      conformational changes as compared to the structure for the RNP-associated
      polymerase, particularly in regions known to interact with the adjacent NP
      monomers in the RNP. Also, the PB2 subunit seems to undergo a substantial
      displacement as a result of the association of the polymerase to RNPs. The
      structural model presented suggests that a core conformation of the polymerase in
      solution exists but the interaction with other partners, such as proteins or RNA,
      will trigger distinct conformational changes to activate new functional
      properties.

PMID- 17517767
TI  - DNA topoisomerase II selects DNA cleavage sites based on reactivity rather than
      binding affinity.
AB  - DNA topoisomerase II modulates DNA topology by relieving supercoil stress and by
      unknotting or decatenating entangled DNA. During its reaction cycle, the enzyme
      creates a transient double-strand break in one DNA segment, the G-DNA. This break
      serves as a gate through which another DNA segment is transported. Defined
      topoisomerase II cleavage sites in genomic and plasmid DNA have been previously
      mapped. To dissect the G-DNA recognition mechanism, we studied the affinity and
      reactivity of a series of DNA duplexes of varied sequence under conditions that
      only allow G-DNA to bind. These DNA duplexes could be cleaved to varying extents
      ranging from undetectable (<0.5%) to 80%. The sequence that defines a cleavage
      site resides within the central 20 bp of the duplex. The DNA affinity does not
      correlate with the ability of the enzyme to cleave DNA, suggesting that the
      binding step does not contribute significantly to the selection mechanism.
      Kinetic experiments show that the selectivity interactions are formed before
      rather than subsequent to cleavage. Presumably the binding energy of the cognate
      interactions is used to promote a conformational change that brings the enzyme
      into a cleavage competent state. The ability to modulate the extent of DNA
      cleavage by varying the DNA sequence may be valuable for future structural and
      mechanistic studies that aim to determine topoisomerase structures with DNA bound
      in pre- and post-cleavage states and to understand the conformational changes
      associated with DNA binding and cleavage.

PMID- 17517768
TI  - Sequence analysis and editing for bisulphite genomic sequencing projects.
AB  - Bisulphite genomic sequencing is a widely used technique for detailed analysis of
      the methylation status of a region of DNA. It relies upon the selective
      deamination of unmethylated cytosine to uracil after treatment with sodium
      bisulphite, usually followed by PCR amplification of the chosen target region.
      Since this two-step procedure replaces all unmethylated cytosine bases with
      thymine, PCR products derived from unmethylated templates contain only three
      types of nucleotide, in unequal proportions. This can create a number of
      technical difficulties (e.g. for some base-calling methods) and impedes manual
      analysis of sequencing results (since the long runs of T or A residues are
      difficult to align visually with the parent sequence). To facilitate the detailed
      analysis of bisulphite PCR products (particularly using multiple cloned
      templates), we have developed a visually intuitive program that identifies the
      methylation status of CpG dinucleotides by analysis of raw sequence data files
      produced by MegaBace or ABI sequencers as well as Staden SCF trace files and
      plain text files. The program then also collates and presents data derived from
      independent templates (e.g. separate clones). This results in a considerable
      reduction in the time required for completion of a detailed genomic methylation
      project.

PMID- 17517769
TI  - QuickSNP: an automated web server for selection of tagSNPs.
AB  - Although large-scale genetic association studies involving hundreds to thousands
      of SNPs have become feasible, the associated cost is substantial. Even with the
      increased efficiency introduced by the use of tagSNPs, researchers are often
      seeking ways to maximize resource utilization given a set of SNP-based gene
      mapping goals. We have developed a web server named QuickSNP in order to provide
      cost-effective selection of SNPs, and to fill in some of the gaps in existing SNP
      selection tools. One useful feature of QuickSNP is the option to select only gene
      centric SNPs from a chromosomal region in an automated fashion. Other useful
      features include automated selection of coding non-synonymous SNPs, SNP filtering
      based on inter-SNP distances and information regarding the availability of
      genotyping assays for SNPs and whether they are present on whole genome chips.
      The program produces user-friendly summary tables and results, and a link to a
      UCSC Genome Browser track illustrating the position of the selected tagSNPs in
      relation to genes and other genomic features. We hope the unique combination of
      features of this server will be useful for researchers aiming to select markers
      for their genotyping studies. The server is freely available and can be accessed
      at the URL http://bioinformoodics.jhmi.edu/quickSNP.pl.

PMID- 17517770
TI  - KinasePhos 2.0: a web server for identifying protein kinase-specific
      phosphorylation sites based on sequences and coupling patterns.
AB  - Due to the importance of protein phosphorylation in cellular control, many
      researches are undertaken to predict the kinase-specific phosphorylation sites.
      Referred to our previous work, KinasePhos 1.0, incorporated profile hidden Markov
      model (HMM) with flanking residues of the kinase-specific phosphorylation sites.
      Herein, a new web server, KinasePhos 2.0, incorporates support vector machines
      (SVM) with the protein sequence profile and protein coupling pattern, which is a
      novel feature used for identifying phosphorylation sites. The coupling pattern
      [XdZ] denotes the amino acid coupling-pattern of amino acid types X and Z that
      are separated by d amino acids. The differences or quotients of coupling strength
      C(XdZ) between the positive set of phosphorylation sites and the background set
      of whole protein sequences from Swiss-Prot are computed to determine the number
      of coupling patterns for training SVM models. After the evaluation based on k
      fold cross-validation and Jackknife cross-validation, the average predictive
      accuracy of phosphorylated serine, threonine, tyrosine and histidine are 90, 93,
      88 and 93%, respectively. KinasePhos 2.0 performs better than other tools
      previously developed. The proposed web server is freely available at
      http://KinasePhos2.mbc.nctu.edu.tw/.

PMID- 17517771
TI  - DSHIFT: a web server for predicting DNA chemical shifts.
AB  - DSHIFT is a web server for predicting chemical shifts of DNA sequences in random
      coil form or double helical B-form. The prediction methods are based on sets of
      published reference chemical shift values and correction factors which account
      for shielding or deshielding effects from neighboring nucleotides. Proton, carbon
      and phosphorus chemical shift predictions are available for random coil DNAs. For
      double helical B-DNA, only proton chemical shift prediction is available. Results
      from these predictions will be useful for facilitating NMR resonance assignments
      and investigating structural features of solution DNA molecules. The URL of this
      server is: http://www.chem.cuhk.edu.hk/DSHIFT.

PMID- 17517772
TI  - RNA chaperone activity of L1 ribosomal proteins: phylogenetic conservation and
      splicing inhibition.
AB  - RNA chaperone activity is defined as the ability of proteins to either prevent
      RNA from misfolding or to open up misfolded RNA conformations. One-third of all
      large ribosomal subunit proteins from E. coli display this activity, with L1
      exhibiting one of the highest activities. Here, we demonstrate via the use of in
      vitro trans- and cis-splicing assays that the RNA chaperone activity of L1 is
      conserved in all three domains of life. However, thermophilic archaeal L1
      proteins do not display RNA chaperone activity under the experimental conditions
      tested here. Furthermore, L1 does not exhibit RNA chaperone activity when in
      complexes with its cognate rRNA or mRNA substrates. The evolutionary conservation
      of the RNA chaperone activity among L1 proteins suggests a functional requirement
      during ribosome assembly, at least in bacteria, mesophilic archaea and eukarya.
      Surprisingly, rather than facilitating catalysis, the thermophilic archaeal L1
      protein from Methanococcus jannaschii (MjaL1) completely inhibits splicing of the
      group I thymidylate synthase intron from phage T4. Mutational analysis of MjaL1
      excludes the possibility that the inhibitory effect is due to stronger RNA
      binding. To our knowledge, MjaL1 is the first example of a protein that inhibits
      group I intron splicing.

PMID- 17517773
TI  - Endonuclease-independent insertion provides an alternative pathway for L1
      retrotransposition in the human genome.
AB  - LINE-1 elements (L1s) are a family of highly successful retrotransposons
      comprising approximately 17% of the human genome, the majority of which have
      inserted through an endonuclease-dependent mechanism termed target-primed reverse
      transcription. Recent in vitro analyses suggest that in the absence of non
      homologous end joining proteins, L1 elements may utilize an alternative,
      endonuclease-independent pathway for insertion. However, it remains unknown
      whether this pathway operates in vivo or in cell lines where all DNA repair
      mechanisms are functional. Here, we have analyzed the human genome to demonstrate
      that this alternative pathway for L1 insertion has been active in recent human
      evolution and characterized 21 loci where L1 elements have integrated without
      signs of endonuclease-related activity. The structural features of these loci
      suggest a role for this process in DNA double-strand break repair. We show that
      endonuclease-independent L1 insertions are structurally distinguishable from
      classical L1 insertion loci, and that they are associated with inter-chromosomal
      translocations and deletions of target genomic DNA.

PMID- 17517774
TI  - Disparate contributions of the Fanconi anemia pathway and homologous
      recombination in preventing spontaneous mutagenesis.
AB  - Fanconi anemia (FA) is a chromosomal instability disorder in which DNA-damage
      processing defects are reported for translesion synthesis (TLS), non-homologous
      end joining (NHEJ) and homologous recombination (HR; both increased and
      decreased). To reconcile these diverse findings, we compared spontaneous
      mutagenesis in FA and HR mutants of hamster CHO cells. In the fancg mutant we
      find a reduced mutation rate accompanied by an increased proportion of deletions
      within the hprt gene. Moreover, in fancg cells gene amplification at the CAD and
      dhfr loci is elevated, another manifestation of inappropriate processing of
      damage during DNA replication. In contrast, the rad51d HR mutant has a greatly
      elevated rate of hprt mutations, >85% of which are deletions. Our analysis
      supports the concept that HR faithfully restores broken replication forks,
      whereas the FA pathway acts more globally to ensure chromosome stability by
      promoting efficient end joining of replication-derived breaks, as well as TLS and
      HR.

PMID- 17517775
TI  - Regulation of glutamate receptor B pre-mRNA splicing by RNA editing.
AB  - RNA-editing enzymes of the ADAR family convert adenosines to inosines in double
      stranded RNA substrates. Frequently, editing sites are defined by base-pairing of
      the editing site with a complementary intronic region. The glutamate receptor
      subunit B (GluR-B) pre-mRNA harbors two such exonic editing sites termed Q/R and
      R/G. Data from ADAR knockout mice and in vitro editing assays suggest an intimate
      connection between editing and splicing of GluR-B pre-mRNA. By comparing the
      events at the Q/R and R/G sites, we can show that editing can both stimulate and
      repress splicing efficiency. The edited nucleotide, but not ADAR binding itself,
      is sufficient to exert this effect. The presence of an edited nucleotide at the
      R/G site reduces splicing efficiency of the adjacent intron facilitating
      alternative splicing events occurring downstream of the R/G site. Lack of editing
      inhibits splicing at the Q/R site. Editing of both the Q/R nucleotide and an
      intronic editing hotspot are required to allow efficient splicing. Inefficient
      intron removal may ensure that only properly edited mRNAs become spliced and
      exported to the cytoplasm.

PMID- 17517776
TI  - Protein knot server: detection of knots in protein structures.
AB  - KNOTS (http://knots.mit.edu) is a web server that detects knots in protein
      structures. Several protein structures have been reported to contain intricate
      knots. The physiological role of knots and their effect on folding and evolution
      is an area of active research. The user submits a PDB id or uploads a 3D protein
      structure in PDB or mmCIF format. The current implementation of the server uses
      the Alexander polynomial to detect knots. The results of the analysis that are
      presented to the user are the location of the knot in the structure, the type of
      the knot and an interactive visualization of the knot. The results can also be
      downloaded and viewed offline. The server also maintains a regularly updated list
      of known knots in protein structures.

PMID- 17517777
TI  - PAP: a comprehensive workbench for mammalian transcriptional regulatory sequence
      analysis.
AB  - Given the recent explosion of publications that employ microarray technology to
      monitor genome-wide expression and that correlate these expression changes to
      biological processes or to disease states, the determination of the
      transcriptional regulation of these co-expressed genes is the next major step
      toward deciphering the genetic network governing the pathway or disease under
      study. Although computational approaches have been proposed for this purpose,
      there is no integrated and user-friendly software application that allows
      experimental biologists to tackle this problem in higher eukaryotes. We have
      previously reported a systematic, statistical model of mammalian transcriptional
      regulatory sequence analysis. We have now made crucial extensions to this model
      and have developed a comprehensive, user-friendly web application suite termed
      the Promoter Analysis Pipeline (PAP). PAP is available at:
      http://bioinformatics.wustl.edu/webTools/portalModule/PromoterSearch.do.

PMID- 17517778
TI  - MAGMA: analysis of two-channel microarrays made easy.
AB  - The web application MAGMA provides a simple and intuitive interface to identify
      differentially expressed genes from two-channel microarray data. While the
      underlying algorithms are not superior to those of similar web applications,
      MAGMA is particularly user friendly and can be used without prior training. The
      user interface guides the novice user through the most typical microarray
      analysis workflow consisting of data upload, annotation, normalization and
      statistical analysis. It automatically generates R-scripts that document MAGMA's
      entire data processing steps, thereby allowing the user to regenerate all results
      in his local R installation. The implementation of MAGMA follows the model-view
      controller design pattern that strictly separates the R-based statistical data
      processing, the web-representation and the application logic. This modular design
      makes the application flexible and easily extendible by experts in one of the
      fields: statistical microarray analysis, web design or software development.
      State-of-the-art Java Server Faces technology was used to generate the web
      interface and to perform user input processing. MAGMA's object-oriented modular
      framework makes it easily extendible and applicable to other fields and
      demonstrates that modern Java technology is also suitable for rather small and
      concise academic projects. MAGMA is freely available at www.magma-fgcz.uzh.ch.

PMID- 17517779
TI  - Conformational changes in the expression domain of the Escherichia coli thiM
      riboswitch.
AB  - The thiM riboswitch contains an aptamer domain that adaptively binds the coenzyme
      thiamine pyrophosphate (TPP). The binding of TPP to the aptamer domain induces
      structural rearrangements that are relayed to a second domain, the so-called
      expression domain, thereby interfering with gene expression. The recently solved
      crystal structures of the aptamer domains of the thiM riboswitches in complex
      with TPP revealed how TPP stabilizes secondary and tertiary structures in the RNA
      ligand complex. To understand the global modes of reorganization between the two
      domains upon metabolite binding the structure of the entire riboswitch in
      presence and absence of TPP needs to be determined. Here we report the secondary
      structure of the entire thiM riboswitch from Escherichia coli in its TPP-free
      form and its transition into the TPP-bound variant, thereby depicting domains of
      the riboswitch that serve as communication links between the aptamer and the
      expression domain. Furthermore, structural probing provides an explanation for
      the lack of genetic control exerted by a riboswitch variant with mutations in the
      expression domain that still binds TPP.

PMID- 17517780
TI  - COMPASS server for remote homology inference.
AB  - COMPASS is a method for homology detection and local alignment construction based
      on the comparison of multiple sequence alignments (MSAs). The method derives
      numerical profiles from given MSAs, constructs local profile-profile alignments
      and analytically estimates E-values for the detected similarities. Until now,
      COMPASS was only available for download and local installation. Here, we present
      a new web server featuring the latest version of COMPASS, which provides (i)
      increased sensitivity and selectivity of homology detection; (ii) longer, more
      complete alignments; and (iii) faster computational speed. After submission of
      the query MSA or single sequence, the server performs searches versus a user
      specified database. The server includes detailed and intuitive control of the
      search parameters. A flexible output format, structured similarly to BLAST and
      PSI-BLAST, provides an easy way to read and analyze the detected profile
      similarities. Brief help sections are available for all input parameters and
      output options, along with detailed documentation. To illustrate the value of
      this tool for protein structure-functional prediction, we present two examples of
      detecting distant homologs for uncharacterized protein families. Available at
      http://prodata.swmed.edu/compass.

PMID- 17517781
TI  - ProSA-web: interactive web service for the recognition of errors in three
      dimensional structures of proteins.
AB  - A major problem in structural biology is the recognition of errors in
      experimental and theoretical models of protein structures. The ProSA program
      (Protein Structure Analysis) is an established tool which has a large user base
      and is frequently employed in the refinement and validation of experimental
      protein structures and in structure prediction and modeling. The analysis of
      protein structures is generally a difficult and cumbersome exercise. The new
      service presented here is a straightforward and easy to use extension of the
      classic ProSA program which exploits the advantages of interactive web-based
      applications for the display of scores and energy plots that highlight potential
      problems spotted in protein structures. In particular, the quality scores of a
      protein are displayed in the context of all known protein structures and
      problematic parts of a structure are shown and highlighted in a 3D molecule
      viewer. The service specifically addresses the needs encountered in the
      validation of protein structures obtained from X-ray analysis, NMR spectroscopy
      and theoretical calculations. ProSA-web is accessible at
      https://prosa.services.came.sbg.ac.at.

PMID- 17517782
TI  - Extracting binary signals from microarray time-course data.
AB  - This article presents a new method for analyzing microarray time courses by
      identifying genes that undergo abrupt transitions in expression level, and the
      time at which the transitions occur. The algorithm matches the sequence of
      expression levels for each gene against temporal patterns having one or two
      transitions between two expression levels. The algorithm reports a P-value for
      the matching pattern of each gene, and a global false discovery rate can also be
      computed. After matching, genes can be sorted by the direction and time of
      transitions. Genes can be partitioned into sets based on the direction and time
      of change for further analysis, such as comparison with Gene Ontology annotations
      or binding site motifs. The method is evaluated on simulated and actual time
      course data. On microarray data for budding yeast, it is shown that the groups of
      genes that change in similar ways and at similar times have significant and
      relevant Gene Ontology annotations.

PMID- 17517783
TI  - WoLF PSORT: protein localization predictor.
AB  - WoLF PSORT is an extension of the PSORT II program for protein subcellular
      location prediction. WoLF PSORT converts protein amino acid sequences into
      numerical localization features; based on sorting signals, amino acid composition
      and functional motifs such as DNA-binding motifs. After conversion, a simple k
      nearest neighbor classifier is used for prediction. Using html, the evidence for
      each prediction is shown in two ways: (i) a list of proteins of known
      localization with the most similar localization features to the query, and (ii)
      tables with detailed information about individual localization features. For
      convenience, sequence alignments of the query to similar proteins and links to
      UniProt and Gene Ontology are provided. Taken together, this information allows a
      user to understand the evidence (or lack thereof) behind the predictions made for
      particular proteins. WoLF PSORT is available at wolfpsort.org.

PMID- 17517784
TI  - RADAR: a web server for RNA data analysis and research.
AB  - RADAR is a web server that provides a multitude of functionality for RNA data
      analysis and research. It can align structure-annotated RNA sequences so that
      both sequence and structure information are taken into consideration during the
      alignment process. This server is capable of performing pairwise structure
      alignment, multiple structure alignment, database search and clustering. In
      addition, RADAR provides two salient features: (i) constrained alignment of RNA
      secondary structures, and (ii) prediction of the consensus structure for a set of
      RNA sequences. RADAR will be able to assist scientists in performing many
      important RNA mining operations, including the understanding of the functionality
      of RNA sequences, the detection of RNA structural motifs and the clustering of
      RNA molecules, among others. The web server together with a software package for
      download is freely accessible at
      http://datalab.njit.edu/biodata/rna/RSmatch/server.htm and
      http://www.ccrnp.ncifcrf.gov/~bshapiro/

PMID- 17517785
TI  - Assisted large fragment insertion by Red/ET-recombination (ALFIRE)--an
      alternative and enhanced method for large fragment recombineering.
AB  - Functional genomics require manipulation and modification of large fragments of
      the genome. Such manipulation has only recently become more efficient due to the
      discovery of different techniques based on homologous recombination. However,
      certain limitations of these strategies still exist since insertion of homology
      arms (HAs) is often based on amplification of DNA sequences with PCR. Large
      quantities of PCR products longer than 4-5 kb can be difficult to obtain and the
      risk of mutations or mismatches increases with the size of the template that is
      being amplified. This can be overcome by adding HAs by conventional cloning
      techniques, but with large fragments such as entire genes the procedure becomes
      time-consuming and tedious. Second, homologous recombination techniques often
      require addition of antibiotic selection genes, which may not be desired in the
      final construct. Here, we report a method to overcome the size and selection
      marker limitations by a two- or three-step procedure. The method can insert any
      fragment into small or large episomes, without the need of an antibiotic
      selection gene. We have humanized the mouse luteinizing hormone receptor gene
      (Lhcgr) by inserting a approximately 55 kb fragment from a BAC clone containing
      the human Lhcgr gene into a 170 kb BAC clone comprising the entire mouse
      orthologue. The methodology is based on the rationale to introduce a counter
      selection cassette flanked by unique restriction sites and HAs for the insert,
      into the vector that is modified. Upon enzymatic digestion, in vitro or in
      Escherichia coli, double-strand breaks are generated leading to recombination
      between the vector and the insert. The procedure described here is thus an
      additional powerful tool for manipulating large and complex genomic fragments.

PMID- 17517786
TI  - In vitro replication and thermodynamic studies of methylation and oxidation
      modifications of 6-thioguanine.
AB  - The cytotoxic effects of thiopurine drugs are mostly exerted through the
      formation of thioguanine nucleotide and its subsequent incorporation into DNA.
      The 6-thioguanine (6-TG) in DNA can be converted to S6-methylthio-2-aminopurine
      (2-AP-6-SCH3) and 2-aminopurine-6-sulfonic acid (2-AP-6-SO3H) upon reaction with
      S-adenosyl-L-methionine and irradiation with UVA light, respectively. Here we
      prepared oligodeoxynucleotides (ODNs) harboring a 6-TG, 2-AP-6-SCH3 or 2-AP-6
      SO3H at a defined site and examined, by using LC-MS/MS, the in vitro replication
      of these substrates with yeast polymerase eta and Klenow fragment (KF-). Our
      results revealed that 2-AP-6-SCH3 could be bypassed by KF-, with significant
      misincorporation of thymine opposite the lesion. The 2-AP-6-SO3H, however,
      blocked markedly the nucleotide insertion by KF-. Yeast pol eta could bypass all
      three modified nucleosides; although dCMP was inserted preferentially, we found
      substantial misincorporation of dTMP and dAMP opposite 2-AP-6-SCH3 and 2-AP-6
      SO3H, respectively. Moreover, both KF- and yeast pol eta induced a considerable
      amount of -2 frameshift products from the replication of 2-AP-6-SCH3- and 2-AP-6
      SO3H-bearing substrates. Our results also underscored the importance of measuring
      the relative ionization efficiencies of replication products in the accurate
      quantification of these products by LC-MS/MS. Moreover, thermodynamic studies
      revealed that 2-AP-6-SCH3 and 2-AP-6-SO3H could cause more destabilization to
      duplex DNA than 6-TG. Taken together, the results from this study shed important
      new light on the biological implications of the two metabolites of 6-TG.

PMID- 17517787
TI  - A facile method for attaching nitroxide spin labels at the 5' terminus of nucleic
      acids.
AB  - In site-directed spin labeling (SDSL), a nitroxide moiety containing a stable,
      unpaired electron is covalently attached to a specific site within a
      macromolecule, and structural and dynamic information at the labeling site is
      obtained via electron paramagnetic resonance (EPR) spectroscopy. Successful SDSL
      requires efficient site-specific incorporation of nitroxides. Work reported here
      presents a new method for facile nitroxide labeling at the 5' terminus of nucleic
      acids of arbitrary sizes. T4-polynucleotide kinase was used to enzymatically
      substitute a phosphorothioate group at the 5' terminus of a nucleic acid, and the
      resulting phosphorothioate was then reacted with an iodomethyl derivative of a
      nitroxide. The method was successfully demonstrated on both chemically
      synthesized and naturally occurring nucleic acids. The attached nitroxides
      reported duplex formation as well as tertiary folding of nucleic acids,
      indicating that they serve as a valid probe in nucleic acid studies.

PMID- 17517788
TI  - Tentacle probes: eliminating false positives without sacrificing sensitivity.
AB  - The majority of efforts to increase specificity or sensitivity in biosensors
      result in trade-offs with little to no gain in overall accuracy. This is because
      a biosensor cannot be more accurate than the affinity interaction it is based on.
      Accordingly, we have developed a new class of reagents based on mathematical
      principles of cooperativity to enhance the accuracy of the affinity interaction.
      Tentacle probes (TPs) have a hairpin structure similar to molecular beacons (MBs)
      for enhanced specificity, but are modified by the addition of a capture probe for
      increased kinetics and affinity. They produce kinetic rate constants up to 200
      fold faster than MB with corresponding stem strengths. Concentration-independent
      specificity was observed with no false positives at up to 1 mM concentrations of
      variant analyte. In contrast, MBs were concentration dependent and experienced
      false positives above 3.88 muM of variant analyte. The fast kinetics of this
      label-free reagent may prove important for extraction efficiency, hence
      sensitivity and detection time, in microfluidic assays. The concentration
      independent specificity of TPs may prove extremely useful in assays where
      starting concentrations and purities are unknown as would be the case in
      bioterror or clinical point of care diagnostics.

PMID- 17517789
TI  - Partially folded conformations of bovine liver glutamate dehydrogenase induced by
      mild acidic conditions.
AB  - The acid-induced unfolding of bovine liver glutamate dehydrogenase (GDH) was
      studied using various spectroscopic methods such as far- and near-UV circular
      dichroism (CD), intrinsic and 1-anilino naphthalene-8-sulphonate (ANS) extrinsic
      fluorescence spectroscopy, light scattering and fluorescence quenching in 20 mM
      mixed buffer at various pHs. CD spectra show that at pH 3.5, GDH retains its
      secondary structure substantially, whereas its tertiary structure content is
      reduced considerably. Intrinsic fluorescence of GDH and ANS binding suggest that,
      at pH 3.5, the hydrophobic surface of enzyme is more exposed in comparison to the
      native form. Acrylamide quenching indicates more exposure of tryptophan residues
      of enzyme at pH 3.5 in comparison to pH 7.5. Another partially unfolded
      intermediate was detected at pH 5.0, which with its ANS binding capacity lies
      between the pH 3.5 intermediate and the native form of the enzyme. Gel filtration
      results revealed that the enzyme at pH 3.5 is dissociated into trimeric species
      whereas it exists as hexamer at pH 7.5 and 5.0. All the data taken together
      suggest the existence of two partially unfolded states of GDH at moderate acidic
      pHs which may be considered as molten and pre-molten globule-like states.

PMID- 17517790
TI  - Secretion expression and activity assay of a novel fusion protein of
      thrombopoietin and interleukin-6 in Pichia pastoris.
AB  - Thrombopoietin (TPO) is an important haematopoietic factor in megakaryocytic
      activities as well as in platelet production. Interleukin 6 (IL-6) can co
      stimulate TPO-dependent formation of colony forming unit of megakaryocyte (CFU
      Meg) growth which could be responsible for residual platelet formation in TPO
      deficient or c-mpl-deficient animals. In this report, we demonstrated the
      development of a high-level expression system to produce a 78-kDa human fusion
      protein IL-6/TPO (named ZH646). This was achieved by constructing the expression
      vector pPICZalpha-A-IL-6-linker-TPO, and obtained the recombinant yeast GS115,
      which then efficiently secreted into a medium with a yield of 30 mg/l from the
      supernatant of the yeast culture in flask. ZH646 was then purified using two
      steps via DEAE-Sephacel chromatography and Mono Q columns. Activity assay showed
      that ZH646 could significantly stimulate the formation of CFU-Meg and the
      proliferation of Dami cells in vitro in a dose-dependent manner. In addition,
      ZH646 also showed thrombopoietic effect in normal mice, and the ability to
      enhance recovery of normal platelet counts after myelosuppression mice. These
      results suggested that ZH646 is a novel protein, and its activities are much
      stronger than that of TPO or IL-6 alone. ZH646 therefore has a broad spectrum of
      megakaryopoiesis activity associated with platelet production.

PMID- 17517791
TI  - Identification of a novel peptide ligand of human vascular endothelia growth
      factor receptor 3 for targeted tumour diagnosis and therapy.
AB  - Human vascular endothelia growth factor receptor 3 (VEGFR-3) is up-regulated in a
      variety of human cancers. It is a potentially rational target for drug delivery.
      To identify novel ligands with specific binding capabilities to VEGFR-3, we
      screened a phage display peptide library and found a consensus motif of the
      peptides which is displayed by the positive phages CSDxxHxWC (x is any amino
      acid). The phage displaying peptide CSDSWHYWC (designated as P1) exhibited the
      highest affinity to VEGFR-3 in phage ELISA and the chemically synthesized P1
      could bind to VEGFR-3 specifically in a dose-dependent manner. In addition, the
      flow cytometry assay and immunofluorescence showed that the FITC labelled P1
      could bind to VEGFR-3 positive carcinoma cells with specificity. Our study
      suggests that P1 may be a homing peptide for treatment of tumours.

PMID- 17517792
TI  - High plasma phosphate as a risk factor for decline in renal function and
      mortality in pre-dialysis patients.
AB  - BACKGROUND: Hyperphosphataemia is associated with increased mortality in patients
      with chronic kidney disease (CKD) stage IV or on dialysis. Furthermore, in animal
      studies, elevated plasma phosphate has been shown to be associated with an
      accelerated decline in renal function. The aim of this study was to determine the
      association of plasma phosphate with renal function loss and mortality in CKD
      stage IV-V pre-dialysis patients with GFR <20 ml/min/1.73 m(2). METHODS: Incident
      pre-dialysis patients were included between 1999 and 2001 in the multi-centre
      PREPARE study, and followed until 2003 or death. Rate of decline in renal
      function for each patient was calculated by linear regression using the
      Modification of Diet in Renal Disease (MDRD) formula to estimate GFR (eGFR).
      RESULTS: A total of 448 patients were included [mean (SD) age 60 (15) years, eGFR
      13 (5.4) ml/min/1.73 m(2), decline in renal function 0.38 (0.95) ml/min/month].
      Phosphate concentration at baseline was 4.71 (1.16) mg/dl, calcium 9.25 (0.77)
      mg/dl and calcium-phosphate product 43.5 (10.9) mg(2)/dl(2). For each mg/dl
      higher phosphate concentration, the mean (95% CI) decline in renal function
      increased with 0.154 (0.071-0.237) ml/min/month. After adjustment, this
      association remained [beta 0.178 (0.082-0.275)]. Seven percent of the patients
      died. Crude mortality risk was 1.25 (0.85-1.84) per mg/dl increase in phosphate,
      which increased to 1.62 (1.02-2.59) after adjustment. CONCLUSIONS: High plasma
      phosphate is an independent risk factor for a more rapid decline in renal
      function and a higher mortality during the pre-dialysis phase. Plasma phosphate
      within the normal range is likely of vital importance in pre-dialysis patients.

PMID- 17517793
TI  - Reversible posterior leukoencephalopathy syndrome (RPLS) in a patient with
      systemic lupus erythematosus (SLE) and lupus nephritis.

PMID- 17517794
TI  - Cigarette smoking and chronic allograft nephropathy.
AB  - BACKGROUND: Smoking has been demonstrated to decrease patient and graft survival
      after kidney transplantation. Data on histological changes associated with
      smoking in renal allografts are lacking. METHODS: Smoking habits before and after
      renal transplantation were evaluated by questionnaire in 279 patients. A
      transplant biopsy was performed more than 1 year after transplantation in 76 of
      them. Histological changes were classified according to Banff 97 criteria. Linear
      regression analysis and proportional odds models for histological changes
      including the factors age, gender, diabetes, body mass index, donor age, time
      since transplantation, history of acute rejection and smoking status were
      calculated. RESULTS: Overall 22% of patients continued smoking after
      transplantation, with the proportion decreasing from 38% of those transplanted
      before 1990 to 13% of those transplanted after 2000. Serum creatinine was non
      significantly higher in smokers (2.3 +/- 2.7 mg/dl vs 1.8 +/- 1.4 mg/dl, P =
      0.21). A renal biopsy was performed in 24% of non-smokers and 39% of smokers (P =
      0.02), and smokers were biopsied on average 1.5 years earlier. Among biopsied
      patients current smokers tended to suffer more often from diabetes (25.0% vs
      13.5%, P = 0.33), to develop transplant failure (33.3% vs 21.2%, P = 0.25) or
      experience a cardiovascular event (29.2% vs 15.4%, P = 0.16). The frequency of
      acute rejection was comparable between smokers and non-smokers (25.0% vs 34.6%, P
      = 0.40). Glomerular sclerosis was associated with diabetes (P = 0.03). Severity
      of vascular intimal fibrous thickening was associated with current smoking (P =
      0.004), whereas the degree of arteriolar hyalinosis (P < 0.001) and
      chronic/sclerosing nephropathy (P = 0.05) were associated with time since
      transplantation. CONCLUSIONS: The number of patients who continue cigarette
      smoking after renal transplantation has decreased in recent years. The main
      allograft lesion associated with smoking is fibrous intimal thickening of small
      arteries.

PMID- 17517795
TI  - A prospective national study of acute renal failure treated with RRT: incidence,
      aetiology and outcomes.
AB  - BACKGROUND: Acute renal failure (ARF) is a diverse condition with no standardized
      definition and is managed in several sub-specialty areas within hospitals. Its
      incidence and aetiology are unknown and studies show a wide range of incidences.
      ARF is becoming more common as the population ages leading to the hypothesis that
      the incidence is much higher than previous estimates. METHODS: This prospective
      population study investigated the incidence, aetiology and outcomes of ARF based
      on a standardized classification of ARF treated by renal replacement therapy
      (RRT) in all sub-specialty areas within hospitals where such treatment takes
      place. Data were collected prospectively on all patients starting RRT for ARF
      within three 12-week periods in 2002. RESULTS: Two hundred eighty-six adults per
      million population (pmp) per year received RRT for ARF. The incidence increased
      with age and pre-existing comorbid illness. Two hundred twelve adults pmp per
      year had no evidence of pre-existing chronic kidney disease (CKD) and the
      remainder had acute on CKD. The median age was 67 years. Fifty-one percent of the
      patients received their first RRT treatment in a critical care setting. Sepsis
      was the most common aetiological insult contributing to ARF in 48% of the
      patients. Mortality was high with 48% dying within 90 days of starting RRT. Age,
      comorbidity, sepsis and recent surgery were independent risk factors for death in
      those with no pre-existing CKD. DISCUSSION: This is the first national study to
      describe ARF treated with RRT in all hospital locations. The hypothesis that ARF
      occurs more frequently than previously thought has been confirmed. This study
      provides data upon which to base effective decision making for prevention,
      patient care and resource planning for patients with ARF.

PMID- 17517796
TI  - Is abdominal surgery still a contraindication for peritoneal dialysis?

PMID- 17517797
TI  - Reduced residual renal function is a risk of peritonitis in continuous ambulatory
      peritoneal dialysis patients.
AB  - BACKGROUND: Loss of residual renal function (RRF) contributes to anaemia,
      inflammation and malnutrition and is also a strong predictor of mortality in
      continuous ambulatory peritoneal dialysis (CAPD) patients. However, the role of
      RRF on peritonitis is not yet clearly established. This study aimed to evaluate
      the effect of RRF on the development of peritonitis. METHODS: Study subjects were
      204 end-stage renal disease (ESRD) patients who started PD from January 2000 to
      December 2005. Biochemical and clinical data within 1 month of PD commencement
      were considered as baseline. To determine risk factors for peritonitis,
      multivariate Cox regression was performed. Kaplan-Meier analysis and log-rank
      test were used to examine the difference of peritonitis-free period according to
      the presence of diabetes and RRF. RESULTS: On univariate analysis based on
      baseline data in first peritonitis, diabetes was less prevalent and RRF (6.7+/
      2.6 vs 4.0+/-2.3 ml/min/1.73 m2, P<0.01), haemoglobin (10.9+/-1.2 vs 10.6+/-1.2
      g/dl, P<0.05) and serum albumin level (3.6+/-0.4 vs 3.4+/-0.4 g/dl, P<0.01) were
      significantly higher in the peritonitis-free group. Kaplan-Meier analysis showed
      that time to first PD peritonitis episode was significantly longer in the non
      diabetic patients (P<0.001) and in patients with higher residual GFR (P<0.001).
      Multivariate analysis showed that diabetes [hazard ratio(HR) 1.64, P<0.05] and
      RRF (per 1 ml/min/1.73 m2 increase, HR 0.81, P<0.01) were independent risk
      factors. CONCLUSION: Our study revealed that RRF and diabetes were risk factors
      for peritonitis. These results suggest that preservation of RRF should be viewed
      as a protective strategy to reduce peritonitis.

PMID- 17517798
TI  - Risk of target lesion revascularization after coronary stenting in patients with
      and without chronic kidney disease.
AB  - BACKGROUND: Rates of restenosis following percutaneous coronary intervention with
      stent placement are high in patients with advanced renal failure. Whether mild to
      moderate chronic kidney disease (CKD) is associated with a similarly increased
      need for short or long-term target lesion revascularization (TLR) following
      coronary stenting is uncertain. METHODS: We analysed results from 1228 patients
      enrolled in four separate, randomized, controlled clinical trials who underwent
      elective coronary angioplasty with stenting and were prospectively followed for 5
      years after the index procedure. Cox proportional hazards regression was used to
      correct for confounding and to estimate the short and long-terms risks of target
      lesion revascularization in patients with vs without mild to moderate CKD.
      RESULTS: During a median follow-up of 5 years, 205 patients (16.7%) required TLR
      with 59 (4.8%) requiring TLR after the first year. Mild (HR 1.07, 95% CI 0.74
      1.53) and moderate (HR 0.95, 95% CI 0.552-1.64) CKD were not associated with an
      increase in the adjusted, overall-risk of TLR. However, mild to moderate CKD was
      associated with a non-significantly increased risk of late TLR (HR 1.40, 95% CI
      0.73-2.69). CONCLUSIONS: Coronary stenting appears to be similarly effective in
      patients with mild to moderate CKD and patients with normal renal function. While
      target lesion revascularization is rarely needed beyond the first year after
      revascularization, long-term results of coronary stenting may be less-favourable
      in patients with CKD.

PMID- 17517799
TI  - Outcomes of surgical revision of stenosed and thrombosed forearm arteriovenous
      fistulae for haemodialysis.
AB  - BACKGROUND: Surgery is an established treatment for stenosed and thrombosed
      forearm arteriovenous fistulae (AVFs), but the literature on its outcome is
      limited. We report our experience of the surgical repair of stenosis in patent
      and thrombosed forearm AVFs and evaluate the outcome of two procedures, proximal
      neo-anastomosis (NEO) vs replacement of the stenosed segment with a
      polytetrafluoroethylene graft interposition (GI). METHODS: Sixty-four stenosed
      forearm AVFs underwent surgery, 32 pre-emptively and 32 post-thrombosis. End
      points of the study were initial success, restenosis and access loss rates. After
      treatment, AVFs were surveilled for restenosis by measuring access flow quarterly
      and performing at least one follow-up angiogram. RESULTS: Initial procedural
      success was 92%; 100% for patent and 84% for thrombosed AVFs. The restenosis rate
      was 0.189 events/AVF-year for both patent and thrombosed AVFs, while the access
      loss rate was 0.016 events/AVF-year in patent and 0.148 in thrombosed AVFs.
      Stenosis was corrected by NEO in 27 AVFs and by GI in 30. The restenosis and
      access loss rates were 0.151 vs 0.214 and 0.033 vs 0.019 events/AVF-year for NEO
      vs GI, respectively. At Cox's hazard analysis, no variable was significantly
      associated with restenosis, while the timing of intervention was the only
      significant determinant of access loss, repaired clotted accesses carrying an 8.0
      fold relative risk of access loss compared with patent AVFs (P=0.048).
      CONCLUSION: Our study shows that surgery remains a valid option for the pre
      emptive repair of stenosis and to salvage clotted forearm AVFs, offering an
      excellent initial success rate and low restenosis rate. It confirms that it is
      better to treat stenosis pre-emptively than post-thrombosis (though the
      restenosis rate appears to be uninfluenced by the timing of intervention) and
      suggests that GI compares favourably with conventional NEO.

PMID- 17517801
TI  - Rapidly progressive renal failure associated with successful pharmacotherapy for
      obesity.

PMID- 17517802
TI  - Agonistic antibody-triggered stimulation of Angiotensin II type 1 receptor and
      renal allograft vascular pathology.

PMID- 17517803
TI  - Coronary spasm: a case of transient ST elevation and syncopal ventricular
      tachycardia without angina.
AB  - We report the case of a 60-year-old male with recurrent pre-syncope, referred
      with a provisional diagnosis of carotid sinus syndrome on the basis of a 4 s
      asystolic pause following carotid sinus massage. On repeat Holter monitoring
      there was ST-segment elevation followed by episodes of polymorphic ventricular
      tachycardia during a mild episode of pre-syncope. Coronary angiography showed
      mild right coronary artery irregularity without significant stenosis. An
      automatic cardioverter defibrillator was implanted and high dose combined
      vasodilator therapy was commenced. At follow-up 18 months after implantation, the
      device has recorded no episode of tachycardia and the patient reports no
      recurrence of symptoms.

PMID- 17517804
TI  - Improvement in cardiac adrenergic function post biventricular pacing for heart
      failure.
AB  - AIMS: We investigated whether biventricular (BiV) pacing favourably affects
      cardiac sympathetic activity in heart failure (HF). METHODS AND RESULTS: In 10 HF
      patients treated with BiV pacing, we assessed cardiac sympathetic activity by
      metaiodobenzylguanidine ((123)I-MIBG) imaging. Patients were randomized in a
      double-blinded crossover fashion, for two weeks of either inactivation of BiV
      pacing or BiV pacing, with crossover to the alternate group for a further two
      weeks. After randomization blocks, cardiac (123)I-MIBG imaging and a 6 min walk
      test were performed. BiV pacing was associated with significant improvements in
      cardiac (123)I-MIBG uptake reflected by increases in early (BiV 1.71 +/- 0.09 vs.
      non-BiV 1.63 +/- 0.06, P = 0.03) and late (at 4 h) heart to mediastinal ratio of
      uptake (BiV 1.54 +/- 0.08 vs. non-BiV 1.45 +/- 0.06, P = 0.03). Additionally,
      pulmonary (123)I-MIBG uptake, measured as lung to mediastinal ratio,
      significantly improved (P = 0.009). Six-minute walk and systolic blood pressure
      tended to improve with BiV vs. non-BiV pacing (P = 0.09). CONCLUSION: In patients
      with stable HF, BiV pacing is associated with long-term improvements in cardiac
      sympathetic nerve activity, as reflected by improvements in cardiac (123)I-MIBG
      uptake. This is a potential mechanism for morbidity and mortality benefits
      observed in larger studies.

PMID- 17517806
TI  - Military fatality rates (by cause) in Afghanistan and Iraq: a measure of
      hostilities.
AB  - BACKGROUND: Military fatalities occur in clusters, and causes differ between
      theatres of operation or within-theatre over time. AIM: Based on around 500
      coalition deaths, identify major causes in Iraq and Afghanistan. For consecutive
      periods (1: May 1 to September 17, 2006, 2: September 18, 2006 to February 4,
      2007), ascertain UK and others' numbers deployed to compare fatality rates per
      1000-personnel years. Take account of clustering: deaths per fatal improvised
      explosive device (IED) incident, and in making short-term projections for
      Afghanistan. METHODS: Cause and date of coalition deaths in Iraq and Afghanistan
      are as listed in http://www.iCasualties.org, where each death is designated as
      hostile or non-hostile. Numbers deployed in 2006 were available for UK and
      Canada, and for US to Iraq. FINDINGS: Out of 537 coalition fatalities in Iraq in
      2006 to September 17, 2006, 457 (85%) were hostile, but only half were in
      Afghanistan (October 2001 to September 17, 2006: 52%, 249/478). Air losses
      accounted for 5% fatalities in Iraq, but 32% in Afghanistan. IEDs claimed three
      out of five hostile deaths in Iraq, only a quarter in Afghanistan. Deaths per
      fatal IED incident averaged 1.5. In period 1, 50/117 military deaths in
      Afghanistan were UK or Canadian from 6750 personnel, a fatality rate of
      19/1000/year, nearly four times the US rate of 5/1000/year in Iraq (based on 280
      deaths). Sixty out of 117 fatalities in Afghanistan occurred as clusters of two
      or more deaths. In period 2, fatality rates changed: down by two-thirds in
      Afghanistan for UK and Canadian forces to 6/1000/year (18 deaths), up by 46% for
      US troops in Iraq to 7.5/1000/year (416 deaths). INTERPRETATION: Rate, and cause,
      of military fatalities are capable of abrupt change, as happened in Iraq (rate)
      and Afghanistan (rate and cause) between consecutive 140-day periods. Forecasts
      can be wide of the mark.

PMID- 17517808
TI  - A field test of three LQAS designs to assess the prevalence of acute
      malnutrition.
AB  - BACKGROUND: The conventional method for assessing the prevalence of Global Acute
      Malnutrition (GAM) in emergency settings is the 30 x 30 cluster-survey. This
      study describes alternative approaches: three Lot Quality Assurance Sampling
      (LQAS) designs to assess GAM. The LQAS designs were field-tested and their
      results compared with those from a 30 x 30 cluster-survey. METHODS: Computer
      simulations confirmed that small clusters instead of a simple random sample could
      be used for LQAS assessments of GAM. Three LQAS designs were developed (33 x 6,
      67 x 3, Sequential design) to assess GAM thresholds of 10, 15 and 20%. The
      designs were field-tested simultaneously with a 30 x 30 cluster-survey in Siraro,
      Ethiopia during June 2003. Using a nested study design, anthropometric, morbidity
      and vaccination data were collected on all children 6-59 months in sampled
      households. Hypothesis tests about GAM thresholds were conducted for each LQAS
      design. Point estimates were obtained for the 30 x 30 cluster-survey and the 33 x
      6 and 67 x 3 LQAS designs. RESULTS: Hypothesis tests showed GAM as <10% for the
      33 x 6 design and GAM as > or =10% for the 67 x 3 and Sequential designs. Point
      estimates for the 33 x 6 and 67 x 3 designs were similar to those of the 30 x 30
      cluster-survey for GAM (6.7%, CI = 3.2-10.2%; 8.2%, CI = 4.3-12.1%, 7.4%, CI =
      4.8-9.9%) and all other indicators. The CIs for the LQAS designs were only
      slightly wider than the CIs for the 30 x 30 cluster-survey; yet the LQAS designs
      required substantially less time to administer. CONCLUSIONS: The LQAS designs
      provide statistically appropriate alternatives to the more time-consuming 30 x 30
      cluster-survey. However, additional field-testing is needed using independent
      samples rather than a nested study design.

PMID- 17517809
TI  - Impact of allocation concealment on conclusions drawn from meta-analyses of
      randomized trials.
AB  - BACKGROUND: Randomized trials without reported adequate allocation concealment
      have been shown to overestimate the benefit of experimental interventions. We
      investigated the robustness of conclusions drawn from meta-analyses to exclusion
      of such trials. MATERIAL: Random sample of 38 reviews from The Cochrane Library
      2003, issue 2 and 32 other reviews from PubMed accessed in 2002. Eligible reviews
      presented a binary effect estimate from a meta-analysis of randomized controlled
      trials as the first statistically significant result that supported a conclusion
      in favour of one of the interventions. METHODS: We assessed the methods sections
      of the trials in each included meta-analysis for adequacy of allocation
      concealment. We replicated each meta-analysis using the authors' methods but
      included only trials that had adequate allocation concealment. Conclusions were
      defined as not supported if our result was not statistically significant.
      RESULTS: Thirty-four of the 70 meta-analyses contained a mixture of trials with
      unclear or inadequate concealment as well as trials with adequate allocation
      concealment. Four meta-analyses only contained trials with adequate concealment,
      and 32, only trials with unclear or inadequate concealment. When only trials with
      adequate concealment were included, 48 of 70 conclusions (69%; 95% confidence
      interval: 56-79%) lost support. The loss of support mainly reflected loss of
      power (the total number of patients was reduced by 49%) but also a shift in the
      point estimate towards a less beneficial effect. CONCLUSION: Two-thirds of
      conclusions in favour of one of the interventions were no longer supported if
      only trials with adequate allocation concealment were included.

PMID- 17517810
TI  - Discrimination and the incidence of psychotic disorders among ethnic minorities
      in The Netherlands.
AB  - BACKGROUND: It is well established now that the incidence of schizophrenia is
      extremely high for several ethnic minority groups in western Europe, but there is
      considerable variation among groups. We investigated whether the increased risk
      among these groups depends upon the degree to which they perceive discrimination
      based on race or ethnicity. METHODS: We studied the incidence of psychotic
      disorders over 7 years in The Hague, a city with a large and diverse population
      of ethnic minorities. To compare the incidence of schizophrenic disorders (DSM
      IV: schizophrenia, schizophreniform disorder, schizoaffective disorder) in each
      ethnic minority group with the incidence in native Dutch, we computed incidence
      rate ratios (IRRs). Based on a population study and on rates of reported
      incidents of discrimination in The Hague, the degree of perceived discrimination
      of ethnic minority groups was rated: high (Morocco), medium (Netherlands
      Antilles, Surinam and 'other non-western countries'), low (Turkey) or very low
      ('western or westernized countries'). RESULTS: The age- and gender-adjusted IRRs
      of schizophrenic disorders for ethnic minority groups exposed to high, medium,
      low, and very low discrimination were 4.00 (95% CI 3.00-5.35), 1.99 (1.58-2.51),
      1.58 (1.10-2.27), and 1.20 (0.81-1.90), respectively. When not only
      schizophrenic, but all psychotic disorders were included in the analysis, the
      results were similar. CONCLUSIONS: These results suggest that discrimination
      perceived by ethnic minority groups in western Europe, or some factor closely
      related to it, may contribute to their increased risk of schizophrenia.

PMID- 17517811
TI  - Socioeconomic circumstances and common mental disorders among Finnish and British
      public sector employees: evidence from the Helsinki Health Study and the
      Whitehall II Study.
AB  - BACKGROUND: Common mental disorders do not always show as consistent
      socioeconomic gradients as severe mental disorders and physical health. This
      inconsistency may be due to the multitude of socioeconomic measures used and the
      populations and national contexts studied. We examine the associations between
      various socioeconomic circumstances and common mental disorders among middle-aged
      Finnish and British public sector employees. METHODS: We used survey data from
      the Finnish Helsinki Health Study (n = 6028) and the British Whitehall II Study
      (n = 3116). Common mental disorders were measured by GHQ-12. The socioeconomic
      indicators were parental education, childhood economic difficulties, own
      education, occupational class, household income, housing tenure and current
      economic difficulties. Logistic regression analysis was the main statistical
      method used. RESULTS: Childhood and current economic difficulties were strongly
      associated with common mental disorders among men and women in both the Helsinki
      and the London cohort. The more conventional indicators of socioeconomic
      circumstances showed weak or inconsistent associations. Differences between the
      two cohorts and two genders were small. CONCLUSIONS: Our findings emphasize the
      importance of past and present economic circumstances to common mental disorders
      across different countries and genders. Overall, our results suggest that among
      employee populations, the socioeconomic patterning of common mental disorders may
      differ from that of other domains of health.

PMID- 17517812
TI  - Estimates of the reproduction numbers of Spanish influenza using morbidity data.
AB  - BACKGROUND: There have been several studies of the transmissibility of the 1918
      (Spanish) influenza virus, which has attributed to >20 million deaths. Many of
      the analyses to date have involved fitting predictions from a transmission model
      to the observed epidemic curves from different settings. METHODS: Using morbidity
      data from cities in Europe and America and from confined settings during the 1918
      influenza pandemic, we contrast the use of several different methods based on the
      growth rate and final size of the epidemic, which do not rely on transmission
      models, to estimate the effective and basic reproduction numbers. RESULTS: The
      effective reproduction number (the average number of secondary infectious cases
      produced by a typical infectious case in a given population) for the 1918
      influenza virus was in the range 1.2-3.0 and 2.1-7.5 for community-based and
      confined settings, respectively. CONCLUSIONS: Assuming further that 30 and 50% of
      individuals were immune to Spanish influenza after the wave in April 1918 and the
      first subsequent wave, respectively, these findings imply that, in a totally
      susceptible population, an infectious case could have led to 2.4-4.3 and 2.6-10.6
      cases in community-based and confined settings, respectively. These findings for
      community-based populations confirm the relatively low transmissibility of the
      1918 (Spanish) influenza virus, which has been found by other studies using
      alternative data sources and methods.

PMID- 17517813
TI  - The impact of passive smoking on the development of lower respiratory tract
      infections in children.
AB  - Environmental tobacco smoke is an important public health problem. The objective
      of this study was to evaluate the effect of passive smoking on lower respiratory
      tract infections (LRTIs) in children aged 2-12 years. A case-control study was
      conducted on matched-pair design. One-hundred and fifty children with LRTIs and
      150 healthy children were included in the study. Data were collected through
      questionnaire and urine samples for the determination of cotinine levels, and
      were analysed by McNemar chi-square, paired t-test and Pearson correlation tests.
      The prevalence of parental self-reported, indoor smoking was 71.3% in children
      with LRTI and 72.0% in healthy children. Employing 30 ng mg(-1), the cut-off
      level of urinary cotinine/creatinine as commonly accepted, 87.3% of the children
      with LRTIs and 84.7% of healthy children were found to be passive smokers (p =
      0.61, odds ratio (OR) = 0.93; confidence interval (CI) = 0.34-2.53). If 60 ng mg(
      1) of urinary cotinine/creatinine was accepted as a cut-off level, it was
      observed that the rates of passive smoking were 76.7% and 50.7%, respectively (p
      = 0.000, OR = 4.72; 95% CI = 2.62-8.52). Dose-dependent exposure to environmental
      tobacco smoke was found to be associated with the incidence of LRTI.

PMID- 17517814
TI  - The use of acacia gum in end stage renal failure.
AB  - OBJECTIVE: To describe a new model for the management of end-stage renal failure
      (ESRF) associated with longest period of dialysis freedom (4-year) achieved with
      this novel form of renal replacement therapy (RRT).The research was done in
      accordance with Helsinki declaration and approved the scientific committee in the
      hospital. Conservative management of chronic renal failure (CRF) can only be
      successful in nonterminal CRF, and patients with ESRF cannot sustain life in the
      absence of renal replacement therapy. A new regimen combining the traditional
      conservative management of CRF (dietary and pharmacologic) with addition of
      Acacia gum (AG) 1 g kg(-1) per day has been reported to provide patients with
      ESRF dialysis freedom. An 11-year-old girl with ESRF initially required four
      sessions of intermittent peritoneal dialysis to control uremic symptoms despite
      conservative measures. The parents refused further treatment by dialysis.
      Thereafter, she was managed with a new regimen combining the traditional
      conservative management of CRF with addition of AG. Four year dialysis and
      improved well-being was achieved. The chronicity of her illness was confirmed by
      the presence of small contracted kidneys, a finding that has not changed during
      the subsequent follow-up. During these 4 years she continued experiencing
      improved well-being and good participation in outdoor activities, had never been
      acidotic or experienced significant uremic symptoms. CONCLUSION: This is the
      longest period of dialysis freedom reported in children with ESRF.

PMID- 17517815
TI  - Evidence behind the WHO guidelines: Hospital Care for Children: what are
      appropriate methods of urine collection in UTI?

PMID- 17517816
TI  - Evidence behind the WHO guidelines: hospital care for children: what is the
      appropriate empiric antibiotic therapy in uncomplicated urinary tract infections
      in children in developing countries?

PMID- 17517817
TI  - Frequency of Chlamydia pneumoniae and Mycoplasma pneumoniae infections in
      children.
AB  - OBJECTIVE: Chlamydia pneumoniae and Mycoplasma pneumoniae are among the most
      important pathogens of acute respiratory infections in children between the ages
      of 5 and 15 years. We aimed to investigate seasonal frequency of respiratory
      infections caused by C. pneumoniae and M. pneumoniae, frequency of coinfection,
      clinical findings and to determine relationship between clinical findings and
      laboratory results. MATERIAL AND METHODS: Total of 284 patients (ranging 5-15
      years of age), admitted to out-patient clinic with symptoms of respiratory tract
      infections between January 2004 and June 2005, were enrolled in the study. IgA,
      IgG and IgM antibodies against C. pneumoniae were quantitatively detected in all
      serum samples by using microimmunofluorescence (MIF). For the M. pneumoniae
      infection an IgM titer in the ELISA test were analyzed. Nasopharyngeal smear
      samples were collected for PCR detection. RESULTS: Mean age was 8 +/- 2.2 (range
      5-14) years. Mycoplasma pneumoniae IgM in 86 (30.2%) cases, C. pneumoniae IgM in
      one (0.3%) case, IgA in six (2.1%) cases and IgG in 10 (3.5%) cases were found
      positive. In 10 (3.5%) cases, both C. pneumoniae IgG (a titer of >1/216) and M.
      pneumoniae IgM were found positive concomitantly. The M. pneumoniae IgM in winter
      was found significantly higher compared to other seasons. Mycoplasma pneumoniae
      PCR method was performed on a total of 203 samples in 33 (16.2%) of which M.
      pneumoniae was found positive. The false positive ratio of PCR technique was
      found 16.2%. In a total of 217 examined samples by PCR method, the DNA of C.
      pneumoniae was found positive in two patients. CONCLUSION: Mycoplasma pneumoniae
      was a common pathogen in respiratory infections. The otherwise C. pneumoniae
      infections were rarely seen in children. A Comparison of serology diagnostic
      tests for M. pneumoniae infections was found more sensitive and specific than
      PCR.

PMID- 17517818
TI  - European health services.

PMID- 17517819
TI  - Are drinkers implicitly positive about drinking alcohol? Personalizing the
      alcohol-IAT to reduce negative extrapersonal contamination.
AB  - AIMS: The advent of indirect measures, such as the Implicit Association test
      (IAT), has stimulated interest in implicit cognitions that may automatically
      steer addictive behaviours such as alcohol abuse. Counter-intuitively, recent IAT
      research has demonstrated that alcohol is implicitly associated with negative
      valence, regardless of the level of alcohol consumption. However, because the IAT
      is susceptible to extrapersonal contamination, this study examined whether
      previous findings reflect contamination of IAT effects by negative extrapersonal
      knowledge rather than personal associations with alcohol. METHODS: Implicit
      alcohol associations were measured with a personalized alcohol-IAT, designed to
      reduce extrapersonal contamination. Whether alcohol associations measured with
      the personalized IAT would predict drinking behaviour above the variance
      explained by self-reported alcohol-related expectancies and attitude was
      examined. RESULTS: In contrast to previous findings with the IAT, the
      personalized IAT yielded positive associations. Moreover, positive alcohol
      associations predicted drinking behaviour above self-reported alcohol
      expectancies and attitudes, demonstrating the incremental validity of the
      personalized IAT. CONCLUSIONS: The present findings support the hypothesis that
      previous findings with the alcohol-IAT at least partly reflect negative
      extrapersonal alcohol-related knowledge, and that implicit alcohol associations
      are positive rather than negative.

PMID- 17517821
TI  - Ethyl glucuronide concentration in hair is not influenced by pigmentation.
AB  - This work shows that the concentration of ethyl glucuronide (EtG) in hair, a
      marker for the evaluation of the alcohol consumption, is not influenced by the
      presence or absence of melanin. The results confirm that, unlike many other
      substances, the EtG determination in hair has not to take into account the hair
      colour for the correct interpretation of hair testing results.

PMID- 17517820
TI  - Prescription procedures in medication for relapse prevention after inpatient
      treatment for alcohol use disorders in Switzerland.
AB  - AIMS: In randomized controlled trials with high internal validity,
      pharmacotherapy using acamprosate, naltrexone, and, to a somewhat lesser extent,
      disulfiram has proved effective in preventing relapse in patients with alcohol
      use disorders (AUD). There remains, however, a paucity of studies with sufficient
      external validity in which the effectiveness of pharmacotherapy in clinical
      practice is investigated. This study aimed to make a contribution to close this
      gap in research. METHODS: In this naturalistic, prospective study, a comparison
      on indices of substance use, psychiatric symptoms, and treatment service
      utilization was carried out using samples of 92 patients who received
      pharmacotherapy and 323 patients who did not receive pharmacotherapy following
      discharge from 12 residential AUD programmes (index stay). RESULTS: Patients that
      received pharmacotherapy were more likely to use alcohol during the index stay
      and at the 1-year follow-up. Moreover, this patient group more readily utilized
      treatment services during a 2-year period prior to and a 1-year period following
      index stay than patients who were not given pharmacotherapy. Nevertheless, when
      pharmacotherapy was prescribed before first post-treatment alcohol use, it was
      associated with delay of alcohol use, fewer relapses, and a reduced need for
      inpatient treatment. In many cases, however, medication was not prescribed until
      alcohol use and relapse had occurred. The length of time to first alcohol use was
      longer, and the cumulative abstinence rate higher, for disulfiram than for
      acamprosate, the latter being generally prescribed for more severely alcohol
      dependent patients. CONCLUSIONS: There is a need for further studies to probe the
      reasons why medication for relapse prevention is not prescribed upon discharge
      from residential treatment and for less severely alcohol-dependent patients.

PMID- 17517822
TI  - Spatial distribution of CYP2B1/2 messenger RNA within the rat liver acinus
      following exposure to the inducers phenobarbital and dieldrin.
AB  - Traditionally, the liver has been considered a homogeneous organ, but literature
      suggests that the cytochromes P450 are differentially distributed among the
      hepatocytes and that the pattern of this distribution is altered by various
      xenobiotics. In this study, the CYP2B1/2 messenger RNA (mRNA) in the hepatocytes
      was compared following treatment of rats with either of two inducers,
      phenobarbital (PB), or dieldrin. Adult male Sprague-Dawley-derived rats were
      treated with either ip PB in saline at 80 mg/kg/day for 5 days or dieldrin in
      corn oil by oral gavage at 2.5 mg/kg/day for 13 days. Control rats received ip
      saline or po corn oil for the same time. Laser capture microdissection (LCM)
      followed by duplex quantitative real-time reverse transcriptase PCR was used to
      measure the CYP2B1/2 mRNA produced in bands of hepatocytes isolated from three
      locations along the sinusoidal path. The amounts of mRNA present in whole liver
      subsamples were also analyzed. CYP2B1/2 enzyme activity was determined by
      assaying 16beta-hydroxytestosterone formation. Whole liver mRNA samples exhibited
      significant induction in CYP2B1/2 transcript levels: sixfold for PB and 2200-fold
      for dieldrin. All the LCM band samples also showed significant fold induction in
      CYP2B1/2 mRNA compared to controls. Dieldrin caused marked increases in CYP2B1/2
      mRNA levels in the direction of blood flow through the acinus: periportal, 300
      fold; midzonal, 600-fold; and centrilobular, 1700-fold. A different pattern of
      induction was observed in the PB-treated rats: periportal, 1800-fold; midzonal,
      8800-fold; and centrilobular, 1600-fold. The present study indicates the
      differences in spatial responses that can be exhibited within the liver following
      exposure to various xenobiotics. It also indicates the importance of examining
      xenobiotic metabolism in the liver in light of its nonhomogeneous, zoned
      microenvironment.

PMID- 17517823
TI  - A proposed mechanism for the protective effect of dioxin against breast cancer.
AB  - Although it is causative for many types of cancers, experimental and
      epidemiological evidence suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (dioxin) may in fact protect against breast cancer. The mechanism(s) for this
      protection remain unclear. In an attempt to further elucidate this mechanism, we
      performed a microarray experiment to identify genes that were modulated upon
      dioxin treatment. We found that dioxin downregulated the messenger RNAs for the G
      protein-coupled receptor, CXCR4, as well as its unique chemokine ligand, CXCL12,
      in MCF-7 breast cancer cells. We demonstrated that the corresponding proteins are
      also downregulated by dioxin. The interaction between CXCR4 and CXCL12 plays a
      central role in the metastasis of breast cancer, as disruption of the
      CXCL12/CXCR4 axis has been shown to limit the metastasis of breast cancer cells
      to the lung in mice. Utilizing an in vitro chemotaxis assay, we demonstrate that
      dioxin specifically inhibits the migration of MCF-7 cells toward CXCL12. We also
      show that dioxin reduces CXCR4 under hypoxia and CXCL12 under estradiol-induced
      conditions in MCF-7 cells. Finally, as the CXCR4/CXCL12 axis is implicated in the
      progression of numerous types of cancer, we identified several other cancer cell
      lines in which dioxin modulates CXCR4 and CXCL12 levels. We therefore propose
      that one mechanism whereby dioxin may protect against breast cancer is via
      downregulation of CXCR4 and CXCL12, thereby inhibiting progression of the
      disease. Further, other nontoxic ligands for the aryl hydrocarbon receptor
      (selective AHR modulators) may exert their protective effects by a similar
      mechanism.

PMID- 17517824
TI  - Promotion of noise-induced cochlear injury by toluene and ethylbenzene in the
      rat.
AB  - Ethylbenzene + toluene are known individually to have ototoxic potential at high
      exposure levels and with prolonged exposure times generally of 4-16 weeks. Both
      ethylbenzene + toluene are minor constituents of JP-8 jet fuel; this fuel has
      recently been determined to promote susceptibility to noise-induced hearing loss.
      Therefore, the current study evaluates the ototoxic potential of combined
      exposure to ethylbenzene + toluene exposure in a ratio calculated from the
      average found in three laboratories. Rats received ethylbenzene + toluene by
      inhalation and half of them were subjected simultaneously to an octave band of
      noise (OBN) of 93-95 dB. Another group received only the noise exposure which was
      designed to produce a small, but permanent auditory impairment while an unexposed
      control group was also included. In two separate experiments, exposures occurred
      either repeatedly on 5 successive days for 1 week or for 5 days on 2 successive
      weeks to 4000 mg/m(3) total hydrocarbons for 6 h based upon initial pilot
      studies. The concentration of toluene was 400 ppm and the concentration of
      ethylbenzene was 660 ppm. Impairments in auditory function were assessed using
      distortion product otoacoustic emissions and compound action potential testing.
      Following completion of these tests, the organs of Corti were dissected to permit
      evaluation of hair cell loss. The uptake and elimination of the solvents was
      assessed by harvesting key organs at two time points following ethylbenzene +
      toluene exposure from additional rats not used for auditory testing. Similarly,
      glutathione (GSH) levels were measured in light of suggestions that oxidative
      stress might result from solvent-noise exposures. Ethylbenzene + toluene exposure
      by itself at 4000 mg/m(3) for 6 h did not impair cochlear function or yield a
      loss of hair cells. However, when combined with a 93-dB OBN exposure combined
      solvent + noise did yield a loss in auditory function and a clear potentiation of
      outer hair cell death that exceeded the loss produced by noise alone. No evidence
      was found for a loss in total GSH in lung, liver, or brain as a consequence of
      ethylbenzene + toluene exposure.

PMID- 17517825
TI  - Globin s-propyl cysteine and urinary N-acetyl-S-propylcysteine as internal
      biomarkers of 1-bromopropane exposure.
AB  - 1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, is a neuro and
      reproductive toxicant in animals and humans. In this study, the dose responses
      for urinary AcPrCys and S-propylcysteine (PrCys) adducts on globin and
      neurofilaments were determined as a function of 1-BP exposure level and duration
      in the rat; and globin PrCys adducts and urinary AcPrCys were quantified in
      samples obtained from workers in a 1-BP production facility. Rats were exposed to
      1-BP by inhalation for 2 weeks at 0, 50, 200, or 800 ppm and to 1-BP at 0 or 50
      ppm for 4 weeks. After the 4-week exposures ended, half of the animals were
      euthanized immediately and half euthanized 8 days later. Urinary AcPrCys was
      measured using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas
      chromatograph-mass spectrometry (GC/MS); and PrCys adducts were determined on
      globin and neurofilaments using LC/MS/MS. In rats, PrCys adduct and urinary
      AcPrCys levels demonstrated a linear dose response relative to exposure level.
      PrCys globin adducts demonstrated a linear cumulative dose response over the 4
      week exposure period. Elimination of AcPrCys appeared biphasic with detectable
      levels still present in urine up to 8 days postexposure. A significant increase
      in globin PrCys adducts was observed in the 1-BP workers relative to control
      workers; and urinary AcPrCys increased with increasing 1-BP ambient exposure
      levels. The results of these studies demonstrate the ability of 1-BP to
      covalently modify proteins in vivo and support the potential of urinary AcPrCys
      and globin PrCys adducts to serve as biomarkers of 1-BP exposure in humans.

PMID- 17517827
TI  - Relationship between embryonic histonic hyperacetylation and axial skeletal
      defects in mouse exposed to the three HDAC inhibitors apicidin, MS-275, and
      sodium butyrate.
AB  - Some histone deacetylase inhibitors (HDACi) have recently been related to
      teratogenic effects in rodents. Skeletal defects have been directly associated
      with embryonic hyperacetylation of somitic nuclei after valproic acid or
      trichostatin A exposure in vivo. Albeit the antitumoral activity of HDACi has
      been classically related to chromatin condensation due to histonic lysine
      hyperacetylation, nonhistonic proteins have also been suggested as an HDACi
      target. The aim of this work was the study of the effects of three HDACi
      (apicidin, API; MS-275; sodium butyrate, BUT) on mouse development and their
      activity on embryonic histonic and nonhistonic proteins. Pregnant mice were ip
      treated with 10 mg/kg body weight API, 25 mg/kg MS-275, 2000 mg/kg BUT or with
      the vehicle alone on day 8 post coitum. Embryos were extracted 1, 2, or 3 h after
      treatment and Western blotting (using antibodies antihyperacetylated histone H4,
      antiacetylated lysine, or antitubulin) and immunohistochemistry (using the
      antibody antihyperacetylated histone H4) were performed. Fetuses, explanted at
      term of gestation, were double stained for bone and cartilage to detect skeletal
      abnormalities. The studied HDACi were teratogenic. The specific axial skeletal
      malformations were fusions or homeotic respecifications. These molecules induced
      hyperacetylation restricted to somitic histones. The hyperacetylation index of
      histone H4 as well as immunohistochemical and skeletal analyses indicated BUT as
      the less active molecule. These new data on effects of API, MS-275, and BUT on
      development suggest histonic hyperacetylation as the mechanism for the induction
      of the observed skeletal abnormalities.

PMID- 17517826
TI  - Transcription of key genes regulating gonadal steroidogenesis in control and
      ketoconazole- or vinclozolin-exposed fathead minnows.
AB  - This study evaluated changes in the expression of steroidogenesis-related genes
      in male fathead minnows exposed to ketoconazole (KTC) or vinclozolin (VZ) for 21
      days. The aim was to evaluate links between molecular changes and higher level
      outcomes after exposure to endocrine-active chemicals (EACs) with different modes
      of action. To aid our analysis and interpretation of EAC-related effects, we
      first examined variation in the relative abundance of steroidogenesis-related
      gene transcripts in the gonads of male and female fathead minnows as a function
      of age, gonad development, and spawning status, independent of EAC exposure.
      Gonadal expression of several genes varied with age and/or gonadal somatic index
      in either males or females. However, with the exception of aromatase,
      steroidogenesis-related gene expression did not vary with spawning status.
      Following the baseline experiments, expression of the selected genes in male
      fathead minnows exposed to KTC or VZ was evaluated in the context of effects
      observed at higher levels of organization. Exposure to KTC elicited changes in
      gene transcription that were consistent with an apparent compensatory response to
      the chemical's anticipated direct inhibition of steroidogenic enzyme activity.
      Exposure to VZ, an antiandrogen expected to indirectly impact steroidogenesis,
      increased pituitary expression of follicle-stimulating hormone beta-subunit as
      well as testis expression of 20beta-hydroxysteroid dehydrogenase and luteinizing
      hormone receptor transcripts. Results of this study contribute to ongoing
      research aimed at understanding responses of the teleost hypothalamic-pituitary
      gonadal axis to different types of EACs and how changes in molecular endpoints
      translate into apical outcomes reflective of either adverse effect or
      compensation.

PMID- 17517828
TI  - Providencia stuartii with VIM-1 metallo-beta-lactamase.

PMID- 17517829
TI  - Survival of HIV-infected patients in the intensive care unit in the era of highly
      active antiretroviral therapy.
AB  - BACKGROUND: Several studies have described improved outcomes for HIV-infected
      patients admitted to the intensive care unit (ICU) since the introduction of
      highly active antiretroviral therapy (HAART). A study was undertaken to examine
      the outcome from the ICU for HIV-infected patients and to identify prognostic
      factors. METHODS: A retrospective study of HIV-infected adults admitted to a
      university affiliated hospital ICU between January 1999 and December 2005 was
      performed. Information was collected on patient demographics, receipt of HAART
      (no patient began HAART on the ICU), reason for ICU admission and hospital
      course. Outcomes were survival to ICU discharge and to hospital discharge.
      RESULTS: 102 patients had 113 admissions to the ICU; HIV infection was newly
      diagnosed in 31 patients. Survival (first episode ICU discharge and hospital
      discharge) was 77% and 68%, respectively, compared with 74% and 65% for general
      medical patients. ICU and hospital survival was 78% and 67% in those receiving
      HAART, and 75% and 66% in those who were not. In univariate analysis, factors
      associated with survival were: haemoglobin (OR = 1.25, 95% CI 1.03 to 1.51, for
      an increase of 1 g/dl), CD4 count (OR = 1.59, 95% CI 0.98 to 2.58, for a 10-fold
      increase in cells/microl), APACHE II score (OR = 0.51, 95% CI 0.29 to 0.90, for a
      10 unit increase) and mechanical ventilation (OR = 0.29, 95% CI 0.10 to 0.83).
      CONCLUSIONS: The outcome for HIV-infected patients admitted to the ICU was good
      and was comparable to that in general medical patients. More than a quarter of
      patients had newly diagnosed HIV infection. Patients receiving HAART did not have
      a better outcome.

PMID- 17517830
TI  - Relationship between air pollution, lung function and asthma in adolescents.
AB  - BACKGROUND: The interrelationships between air pollution, lung function and the
      incidence of childhood asthma have yet to be established. A study was undertaken
      to determine whether lung function is associated with new onset asthma and
      whether this relationship varies by exposure to ambient air pollutants. METHODS:
      A cohort of children aged 9-10 years without asthma or wheeze at study entry were
      identified from the Children's Health Study and followed for 8 years. The
      participants resided in 12 communities with a wide range of ambient air
      pollutants that were measured continuously. Spirometric testing was performed and
      a medical diagnosis of asthma was ascertained annually. Proportional hazard
      regression models were fitted to investigate the relationship between lung
      function at study entry and the subsequent development of asthma and to determine
      whether air pollutants modify these associations. RESULTS: The level of airway
      flow was associated with new onset asthma. Over the 10th-90th percentile range of
      forced expiratory flow over the mid-range of expiration (FEF(25-75), 57.1%), the
      hazard ratio (HR) of new onset asthma was 0.50 (95% CI 0.35 to 0.71). This
      protective effect of better lung function was reduced in children exposed to
      higher levels of particulate matter with an aerodynamic diameter <2.5 microm
      (PM(2.5)). Over the 10th-90th percentile range of FEF(25-75), the HR of new onset
      asthma was 0.34 (95% CI 0.21 to 0.56) in communities with low PM(2.5) (<13.7
      microg/m(3)) and 0.76 (95% CI 0.45 to 1.26) in communities with high PM(2.5) (>
      or = 13.7 microg/m(3)). A similar pattern was observed for forced expiratory
      volume in 1 s. Little variation in HR was observed for ozone. CONCLUSION:
      Exposure to high levels of PM(2.5) attenuates the protective effect of better
      lung function against new onset asthma.

PMID- 17517831
TI  - Diphenyl furans and aza analogs: effects of structural modification on in vitro
      activity, DNA binding, and accumulation and distribution in trypanosomes.
AB  - Human African trypanosomiasis is a devastating disease with only a few treatment
      options, including pentamidine. Diamidine compounds such as pentamidine, DB75,
      and DB820 are potent antitrypanosomal compounds. Previous investigations have
      shown that diamidines accumulate to high concentrations in trypanosomes. However,
      the mechanism of action of this class of compounds remains unknown. A long
      hypothesized mechanism of action has been binding to DNA and interference with
      DNA-associated enzymes. The fluorescent diamidines, DB75 and DB820, have been
      shown to localize not only in the DNA-containing nucleus and kinetoplast of
      trypanosomes but also to the acidocalcisomes. Here we investigate two series of
      analogs of DB75 and DB820 with various levels of in vitro antitrypanosomal
      activity to determine whether any correlation exists between trypanosome
      accumulation, distribution, and in vitro activity. Despite wide ranges of in
      vitro antitrypanosomal activity, all of the compounds investigated accumulated to
      millimolar concentrations in trypanosomes over a period of 8 h. Interestingly,
      some of the less potent compounds accumulated to concentrations much higher than
      those of more potent compounds. All of the compounds were localized to the DNA
      containing nucleus and/or kinetoplast, and many were also found in the
      acidocalcisomes. Accumulation in the nucleus and kinetoplast should be important
      to the mechanism of action of these compounds. The acidocalcisomes may also play
      a role in the mechanism of action of these compounds. This investigation suggests
      that the extent of accumulation alone is not responsible for killing trypanosomes
      and that organelle-specific accumulation may not predict in vitro activity.

PMID- 17517832
TI  - Pegylated interferon Alfa-2b monotherapy and pegylated interferon Alfa-2b plus
      lamivudine combination therapy for patients with hepatitis B virus E antigen
      negative chronic hepatitis B.
AB  - Forty-eight hepatitis B virus (HBV) E antigen-negative chronic hepatitis B
      patients received pegylated interferon alfa-2b either alone or with lamivudine
      for 48 weeks and were followed for an additional 24 weeks. At the end of follow
      up, virological response rates (HBV DNA levels of <400 copies/ml) were similar in
      the monotherapy (24%) and combination therapy (26%) groups.

PMID- 17517833
TI  - Interdomain loop mutation Asp190Cys of the tetracycline efflux transporter
      TetA(B) decreases affinity for substrate.

PMID- 17517834
TI  - Location of persisting mycobacteria in a Guinea pig model of tuberculosis
      revealed by r207910.
AB  - The lengthy chemotherapy of tuberculosis reflects the ability of a small
      subpopulation of Mycobacterium tuberculosis bacteria to persist in infected
      individuals. To date, the exact location of these persisting bacteria is not
      known. Lung lesions in guinea pigs infected with M. tuberculosis have striking
      similarities, such as necrosis, mineralization, and hypoxia, to natural
      infections in humans. Guinea pigs develop necrotic primary lesions after aerosol
      infection that differ in their morphology compared to secondary lesions resulting
      from hematogenous dissemination. In infected guinea pigs conventional therapy for
      tuberculosis during 6 weeks reduced the bacterial load by 1.7 logs in the lungs
      and, although this completely reversed lung inflammation associated with
      secondary lesions, the primary granulomas remained largely unaffected. Treatment
      of animals with the experimental drug R207910 (TMC207) for 6 weeks was highly
      effective with almost complete eradication of the bacteria throughout both the
      primary and the secondary lesions. Most importantly, the few remnants of acid
      fast bacilli remaining after R207910 treatment were to be found extracellular, in
      a microenvironment of residual primary lesion necrosis with incomplete dystrophic
      calcification. This zone of the primary granuloma is hypoxic and is
      morphologically similar to what has been described for human lung lesions. These
      results show that this acellular rim may, therefore, be a primary location of
      persisting bacilli withstanding drug treatment.

PMID- 17517835
TI  - Effects of rifampin and multidrug resistance gene polymorphism on concentrations
      of moxifloxacin.
AB  - Treatment regimens combining moxifloxacin and rifampin for drug-susceptible
      tuberculosis are being studied intensively. However, rifampin induces enzymes
      that transport and metabolize moxifloxacin. We evaluated the effect of rifampin
      and the human multidrug resistance gene (MDR1) C3435T polymorphisms (P
      glycoprotein) on moxifloxacin pharmacokinetic parameters. This was a single
      center, sequential design study with 16 volunteers in which sampling was
      performed after four daily oral doses of moxifloxacin (400 mg) and again after 10
      days of combined rifampin (600 mg) and moxifloxacin. After daily coadministration
      of rifampin, the area under the concentration-time curve from 0 to 24 h (AUC(0
      24)) for moxifloxacin decreased 27%. Average bioequivalence between moxifloxacin
      coadministered with rifampin and moxifloxacin alone was not demonstrated: the
      ratio of geometric means (RGM) of the moxifloxacin AUC(0-24) was 73.3 (90%
      confidence intervals [CI], 64.3, 83.5) (total P value, 0.87 for two one-sided t
      tests). Peak moxifloxacin concentrations, however, were equivalent: the RGM of
      the maximum concentration of the drug in serum was 93.6 (90% CI, 80.2, 109.3)
      (total P value, 0.049). Concentrations of the sulfate conjugate metabolite of
      moxifloxacin were increased twofold following rifampin coadministration (AUC(0
      24), 1.29 versus 2.79 mug.h/ml). Concomitant rifampin administration resulted in
      a 27% decrease in the mean moxifloxacin AUC(0-24) and a marked increase in the
      AUC(0-24) of the microbiologically inactive M1 metabolite. Additional studies are
      required to understand the clinical significance of the moxifloxacin-rifampin
      interaction.

PMID- 17517836
TI  - In vitro activities of 15 antimicrobial agents against 110 toxigenic clostridium
      difficile clinical isolates collected from 1983 to 2004.
AB  - The incidence and severity of Clostridium difficile-associated disease (CDAD) is
      increasing, and standard treatment is not always effective. Therefore, more
      effective antimicrobial agents and treatment strategies are needed. We used the
      agar dilution method to determine the in vitro susceptibility of the following
      antimicrobials against 110 toxigenic clinical isolates of C. difficile from 1983
      to 2004, primarily from the United States: doripenem, meropenem, gatifloxacin,
      levofloxacin, moxifloxacin, OPT-80, ramoplanin, rifalazil, rifaximin,
      nitazoxanide, tizoxanide, tigecycline, vancomycin, tinidazole, and metronidazole.
      Included among the isolates tested were six strains of the toxinotype III,
      NAP1/BI/027 group implicated in recent U.S., Canadian, and European outbreaks.
      The most active agents in vitro were rifaximin, rifalazil, tizoxanide,
      nitazoxanide, and OPT-80 with MICs at which 50% of the isolates are inhibited
      (MIC(50)) and MIC(90) values of 0.0075 and 0.015 microg/ml, 0.0075 and 0.03
      microg/ml, 0.06 and 0.125 microg/ml, 0.06 and 0.125 microg/ml, 0.125 and 0.125
      microg/ml, respectively. However, for three isolates the rifalazil and rifaximin
      MICs were very high (MIC of >256 microg/ml). Ramoplanin, vancomycin, doripenem,
      and meropenem were also very active in vitro with narrow MIC(50) and MIC(90)
      ranges. None of the isolates were resistant to metronidazole, the only agent for
      which there are breakpoints, with tinidazole showing nearly identical results.
      These in vitro susceptibility results are encouraging and support continued
      evaluation of selected antimicrobials in clinical trials of treatment for CDAD.

PMID- 17517838
TI  - First occurrence of an Escherichia coli clinical isolate producing the VIM-1/VIM
      2 hybrid metallo-beta-lactamase VIM-12.

PMID- 17517837
TI  - Impact of resistance selection and mutant growth fitness on the relative
      efficacies of streptomycin and levofloxacin for plague therapy.
AB  - Yersinia pestis, the bacterium that causes plague, is a potential agent of
      biowarfare and bioterrorism. The aminoglycoside antibiotic streptomycin is the
      gold standard for treatment. However, this recommendation is based on scant
      animal and clinical data. We used an in vitro pharmacodynamic infection model to
      compare the efficacies of 10-day regimens of streptomycin versus the
      fluoroquinolone antibiotic levofloxacin for the treatment of Y. pestis infection
      and to evaluate for emergence of resistance. The human serum concentration-time
      profiles for standard clinical regimens of 1 g of streptomycin given every 12 h
      and 500 mg of levofloxacin given every 24 h were simulated. The growth fitness of
      drug-resistant mutants was examined in neutropenic and immunocompetent mouse
      thigh infection models. In the in vitro infection system, untreated bacteria grew
      from 10(7) to 10(10) CFU/ml. Streptomycin therapy caused a 10(5) CFU/ml reduction
      in the number of bacteria over 24 h, followed by regrowth with streptomycin
      resistant mutants. Levofloxacin resulted in a 10(7) CFU/ml reduction in the
      number of bacteria within 12 h, ultimately sterilizing the culture without
      resistance selection. In both the normal and neutropenic mouse infection models,
      streptomycin-resistant and wild-type strains were equally fit. However, 90% of
      levofloxacin-resistant isolates, cultured from the control in vitro infection
      arm, did not proliferate in the mouse models. Thus, the fluoroquinolone
      antibiotic levofloxacin was superior to streptomycin in our in vitro infection
      model. The majority of levofloxacin-resistant mutants were less fit than
      streptomycin-resistant and wild-type Y. pestis.

PMID- 17517839
TI  - Increased expression of ampC in Pseudomonas aeruginosa mutants selected with
      ciprofloxacin.
AB  - Two Pseudomonas aeruginosa mutants exhibiting increased expression of ampC were
      selected during exposure to ciprofloxacin. These mutants also exhibited
      significant increases in mexCD-oprJ expression, but further studies failed to
      show a link between the increased expression of mexCD-oprJ and ampC. Increased
      ampC expression was not related to mutations within ampR, the ampC-ampR
      intergenic region, ampD, ampDh2, or ampDh3 or to changes in the levels of
      expression of these amidase genes. However, ampD complementation restored wild
      type levels of ampC expression and ceftazidime susceptibility, suggesting
      alternative mechanisms of ampC regulation.

PMID- 17517840
TI  - Measurement of voriconazole activity against Candida albicans, C. glabrata, and
      C. parapsilosis isolates using time-kill methods validated by high-performance
      liquid chromatography.
AB  - We developed a high-performance liquid chromatography (HPLC) assay to validate
      time-kill and postantifungal-effect (PAFE) experiments for voriconazole against
      Candida albicans, Candida glabrata, and Candida parapsilosis isolates.
      Voriconazole exerted prolonged fungistatic activity but no PAFE at concentrations
      achievable in human sera. HPLC confirmed that experiments were conducted at the
      desired steady-state voriconazole concentrations.

PMID- 17517841
TI  - Target gene sequencing to characterize the penicillin G susceptibility of
      Neisseria meningitidis.
AB  - Clinical isolates of Neisseria meningitidis with reduced susceptibility to
      penicillin G (intermediate isolates, Pen(I)) harbor alterations in the penA gene
      encoding the penicillin binding protein 2 (PBP2). A 402-bp DNA fragment in the 3'
      half of penA was sequenced from a collection of 1,670 meningococcal clinical
      isolates from 22 countries that spanned 60 years. Phenotyping, genotyping, and
      the determination of MICs of penicillin G were also performed. A total of 139
      different penA alleles were detected with 38 alleles that were highly related,
      clustered together in maximum-likelihood analysis and corresponded to the
      penicillin G-susceptible isolates. The remaining 101 penA alleles were highly
      diverse, corresponded to different genotypes or phenotypes, and accounted for 38%
      of isolates, but no clonal expansion was detected. Analysis of the altered
      alleles that were represented by at least five isolates showed high correlation
      with the Pen(I) phenotype. The deduced amino acid sequence of the corresponding
      PBP2 comprised five amino acid residues that were always altered. This
      correlation was not complete for rare alleles, suggesting that other mechanisms
      may also be involved in conferring reduced susceptibility to penicillin. Evidence
      of mosaic structures through events of interspecies recombination was also
      detected in altered alleles. A new website was created based on the data from
      this work (http://neisseria.org/nm/typing/penA). These data argue for the use of
      penA sequencing to identify isolates with reduced susceptibility to penicillin G
      and as a tool to improve typing of meningococcal isolates, as well as to analyze
      DNA exchange among Neisseria species.

PMID- 17517842
TI  - Single-dose pharmacokinetics of intravenous itraconazole and hydroxypropyl-beta
      cyclodextrin in infants, children, and adolescents.
AB  - This investigation was designed to evaluate the single-dose pharmacokinetics of
      itraconazole, hydroxyitraconazole, and hydroxypropyl-beta-cyclodextrin (HP-beta
      CD) after intravenous administration to children at risk for fungal infection.
      Thirty-three children aged 7 months to 17 years received a single dose of
      itraconazole (2.5 mg/kg in 0.1-g/kg HP-beta-CD) administered over 1 h by
      intravenous infusion. Plasma samples for the determination of the analytes of
      interest were drawn over 120 h and analyzed by high-pressure liquid
      chromatography, and the pharmacokinetics were determined by traditional
      noncompartmental analysis. Consistent with the role of CYP3A4 in the
      biotransformation of itraconazole, a substantial degree of variability was
      observed in the pharmacokinetics of this drug after IV administration. The
      maximum plasma concentrations (C(max)) for itraconazole, hydroxyitraconazole, and
      HP-beta-CD averaged 1,015 +/- 692 ng/ml, 293 +/- 133 ng/ml, and 329 +/- 200
      mug/ml, respectively. The total body exposures (area under the concentration-time
      curve from 0 to 24 h) for itraconazole, hydroxyitraconazole, and HP-beta-CD
      averaged 4,922 +/- 6,784 ng.h/ml, 3,811 +/- 2,794 ng.h/ml, and 641.5 +/- 265.0
      mug.h/ml, respectively, with no significant age dependence observed among the
      children evaluated. Similarly, there was no relationship between age and total
      body clearance (702.8 +/- 499.4 ml/h/kg); however, weak associations between age
      and the itraconazole distribution volume (r(2) = 0.18, P = 0.02), C(max) (r(2) =
      0.14, P = 0.045), and terminal elimination rate (r(2) = 0.26, P < 0.01) were
      noted. Itraconazole infusion appeared to be well tolerated in this population
      with a single adverse event (stinging at the site of infusion) deemed to be
      related to study drug administration. Based on the findings of this
      investigation, it appears that intravenous itraconazole can be administered to
      infants beyond 6 months, children, and adolescents using a weight-normalized
      approach to dosing.

PMID- 17517843
TI  - Experimental phage therapy against Staphylococcus aureus in mice.
AB  - The present study describes a bacteriophage (M(Sa)) active against Staphylococcus
      aureus, including methicillin-resistant staphylococcal strains. When inoculated
      into mice simultaneously with S. aureus A170 (10(8) CFU/mouse), phage (10(9) PFU)
      rescued 97% of the mice; when applied to nonlethal (5 x 10(6) CFU/mouse) 10-day
      infections, the phage also fully cleared the bacteria. The phage M(Sa), delivered
      inside macrophages by S. aureus, kills the intracellular staphylococci in vivo
      and in vitro. The phage can also prevent abscess formation and reduce the
      bacterial load and weight of abscesses. These results suggest a potential use of
      the phage for the control of both local and systemic human S. aureus infections.

PMID- 17517844
TI  - Systematic derivation of marker sets for staphylococcal cassette chromosome mec
      typing.
AB  - The aim of this study was to identify optimized sets of genotyping targets for
      the staphylococcal cassette chromosome mec (SCCmec). We analyzed the gene
      contents of 46 SCCmec variants in order to identify minimal subsets of targets
      that provide useful resolution. This was achieved by firstly identifying and
      characterizing each available SCCmec element based on the presence or absence of
      34 binary targets. This information was used as input for the software "Minimum
      SNPs," which identifies the minimum number of targets required to differentiate a
      set of genotypes up to a predefined Simpson's index of diversity (D) value. It
      was determined that 22 of the 34 targets were required to genotype the 46 SCCmec
      variants to a D of 1. The first 6, 9, 12, and 15 targets were found to define 21,
      29, 35, and 39 SCCmec variants, respectively. The genotypes defined by these
      marker subsets were largely consistent with the relationships between SCCmec
      variants and the accepted nomenclature. Consistency was made virtually complete
      by forcing the computer program to include ccr1 and ccr5 in the target set. An
      alternative target set biased towards discriminating abundant SCCmec variants was
      derived by analyzing an input file in which common SCCmec variants were repeated,
      thus ensuring that markers that discriminate abundant variants had a large effect
      on D. Finally, it was determined that mecA single nucleotide polymorphisms (SNPs)
      can increase the overall genotyping resolution, as different mecA alleles were
      found in otherwise identical SCCmec variants.

PMID- 17517845
TI  - Inhaled large porous particles of capreomycin for treatment of tuberculosis in a
      guinea pig model.
AB  - Capreomycin is used for the treatment of multidrug-resistant tuberculosis (MDR
      TB), but it is limited therapeutically by its severe side effects. The objectives
      of the present studies were (i) to design low-density porous capreomycin sulfate
      particles for efficient pulmonary delivery to improve local and systemic drug
      bioavailability and capacity to reduce the bacillary load in the lungs in a
      manner similar to that achieved with intramuscular injections; (ii) to determine
      pharmacokinetic parameters after pulmonary administration of these capreomycin
      particles; and (iii) to evaluate the efficacy of these particles in treating
      animals in a small-aerosol-inoculum guinea pig model of TB. Capreomycin particles
      were manufactured by spray drying and characterized in terms of size and drug
      content. Pharmacokinetic parameters were determined by noncompartmental methods
      with healthy guinea pigs after administration of capreomycin particles by
      insufflation. The efficacy of the particles was evaluated by histopathological
      analysis and in terms of wet organ weight and bacterial burden in TB-infected
      animals. Lungs of animals receiving a 14.5-mg/kg dose of capreomycin particles
      showed significantly lower wet weights and smaller bacterial burdens than those
      of animals receiving any other treatment. These results were supported by
      histopathological analysis. The feasibility of inhaling capreomycin in a novel
      powder form, with the ultimate objective of the treatment of MDR-TB, is
      demonstrated by pharmacokinetic and pharmacodynamic studies with guinea pigs. If
      applied to humans with MDR-TB, such a therapeutic approach might simplify drug
      delivery by eliminating injections and might reduce adverse effects through
      lowering the dose.

PMID- 17517846
TI  - High-affinity, human antibody-like antibody fragment (single-chain variable
      fragment) neutralizing the lethal factor (LF) of Bacillus anthracis by inhibiting
      protective antigen-LF complex formation.
AB  - The anthrax lethal toxin (LT) consists of two subunits, the protective antigen
      (PA) and the lethal factor (LF), and is essential for anthrax pathogenesis.
      Several recombinant antibodies directed against PA and intended for medical use
      have been obtained, but none against LF, despite the recommendations of anthrax
      experts. Here we describe an anti-LF single-chain variable fragment (scFv) that
      originated from an immunized macaque (Macaca fascicularis) and was obtained by
      phage display. Panning of the library of 1.8 x 10(8) clones allowed the isolation
      of 2LF, a high-affinity (equilibrium dissociation constant, 1.02 nM) scFv, which
      is highly neutralizing in the standardized in vitro assay (50% inhibitory
      concentration, 1.20 +/- 0.06 nM) and in an in vivo assay. The scFv neutralizes
      anthrax LT by inhibiting the formation of the LF-PA complex. The genes encoding
      2LF are very similar to those of human immunoglobulin germ line genes, sharing
      substantial (84.2%) identity with their most similar, germinally encoded
      counterparts; this feature favors medical applications. These results, and others
      formerly published, demonstrate that our approach can generate antibody fragments
      suitable for prophylaxis and therapeutics.

PMID- 17517847
TI  - In vitro interactions between apricitabine and other deoxycytidine analogues.
AB  - Apricitabine is a novel deoxycytidine analogue reverse transcriptase inhibitor
      that is under development for the treatment of human immunodeficiency virus type
      1 (HIV-1) infection. Apricitabine is phosphorylated to its active triphosphate by
      deoxycytidine kinase, which is also responsible for the intracellular
      phosphorylation of lamivudine (3TC) and emtricitabine (FTC); hence, in vitro
      studies were performed to investigate possible interactions between apricitabine
      and these agents. Human peripheral blood mononuclear cells (PBMC) were incubated
      for 24 h with various concentrations of (3)H-labeled or unlabeled apricitabine,
      3TC, or FTC. Intracellular concentrations of parent compounds and their
      phosphorylated derivatives were measured by high-performance liquid
      chromatography. In other experiments, viral reverse transcriptase activity was
      measured in PBMC infected with HIV-1 bearing M184V in the presence of various
      concentrations of apricitabine and 3TC. [(3)H]apricitabine and [(3)H]3TC were
      metabolized intracellularly to form mono-, di-, and triphosphates. 3TC and FTC (1
      to 10 microM) produced concentration-dependent decreases in apricitabine
      phosphorylation; in contrast, apricitabine at concentrations of up to 30 muM had
      no effect on the phosphorylation of 3TC or FTC. The combination of apricitabine
      and 3TC reduced the antiviral activity of apricitabine against HIV-1:
      apricitabine concentrations producing 50% inhibition of viral reverse
      transcriptase were increased two- to fivefold in the presence of 3TC. These
      findings suggest that nucleoside reverse transcriptase inhibitors with similar
      modes of action may show biochemical interactions that affect their antiviral
      efficacy. It is therefore essential that potential interactions between
      combinations of new and existing agents be thoroughly investigated before such
      combinations are introduced into clinical practice.

PMID- 17517848
TI  - Fosamprenavir plus ritonavir increases plasma ketoconazole and ritonavir
      exposure, while amprenavir exposure remains unchanged.
AB  - Plasma ketoconazole (KETO), amprenavir (APV), and ritonavir (RTV)
      pharmacokinetics were evaluated in 15 healthy subjects after being treated with
      KETO at 200 mg once daily (QD), fosamprenavir (FPV)/RTV at 700/100 mg twice daily
      (BID), and then KETO at 200 mg QD plus FPV/RTV at 700/100 mg BID in this open
      label study. The KETO area under the concentration-time curve at steady state was
      increased 2.69-fold with FPV/RTV. APV exposure was unchanged, and RTV exposure
      was slightly increased.

PMID- 17517849
TI  - Early bactericidal activity of high-dose rifampin in patients with pulmonary
      tuberculosis evidenced by positive sputum smears.
AB  - We studied the early bactericidal activity of twice the standard dose of rifampin
      in subjects with pulmonary tuberculosis evidenced by positive smears. The
      observed mean 2-day activity was almost double that reported at the standard
      dose. Further studies are warranted to establish whether higher rifampin doses
      might assist in shortening tuberculosis treatment.

PMID- 17517850
TI  - Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy
      subjects.
AB  - The population pharmacokinetics of tafenoquine were studied in Australian
      soldiers taking tafenoquine for malarial prophylaxis. The subjects (476 males and
      14 females) received a loading dose of 200 mg tafenoquine base daily for 3 days,
      followed by a weekly dose of 200 mg tafenoquine for 6 months. Blood samples were
      collected from each subject after the last loading dose and then at weeks 4, 8,
      and 16. Plasma tafenoquine concentrations were determined by liquid
      chromatography-tandem mass spectrometry. Population modeling was performed with
      NONMEM, using a one-compartment model. Typical values of the first-order
      absorption rate constant (K(a)), clearance (CL/F), and volume of distribution
      (V/F) were 0.243 h(-1), 0.056 liters/h/kg, and 23.7 liters/kg, respectively. The
      intersubject variability (coefficient of variation) in CL/F and V/F was 18% and
      22%, respectively. The interoccasion variability in CL/F was 18%, and the mean
      elimination half-life was 12.7 days. A positive linear association between weight
      and both CL/F and V/F was found, but this had insufficient impact to warrant
      dosage adjustments. Model robustness was assessed by a nonparametric bootstrap
      (200 samples). A degenerate visual predictive check indicated that the raw data
      mirrored the postdose concentration-time profiles simulated (n = 1,000) from the
      final model. Individual pharmacokinetic estimates for tafenoquine did not predict
      the prophylactic outcome with the drug for four subjects who relapsed with
      Plasmodium vivax malaria, as they had similar pharmacokinetics to those who were
      free of malaria infection. No obvious pattern existed between the plasma
      tafenoquine concentration and the pharmacokinetic parameter values for subjects
      with and without drug-associated moderate or severe adverse events. This
      validated population pharmacokinetic model satisfactorily describes the
      disposition and variability of tafenoquine used for long-term malaria prophylaxis
      in a large cohort of soldiers on military deployment.

PMID- 17517851
TI  - Novel complex class 1 integron bearing an ISCR1 element in an Escherichia coli
      isolate carrying the blaCTX-M-14 gene.
AB  - This work identifies an ISCR1-related bla(CTX-M-14) gene, which has never been
      reported before, from a clinical isolate of Escherichia coli. The bla(CTX-M-14)
      gene was preceded by an ISCR1 element that was followed by a class 1 integron
      containing three different insert gene cassettes, i.e., dfrA12, orfF, and aadA2.

PMID- 17517852
TI  - Effects of the translocation status of human immunodeficiency virus type 1
      reverse transcriptase on the efficiency of excision of tenofovir.
AB  - The ATP-dependent phosphorolytic excision of nucleoside analogue reverse
      transcriptase inhibitors can diminish their inhibitory effects on human
      immunodeficiency virus replication. Previous studies have shown that excision can
      occur only when the reverse transcriptase complex exists in its
      pretranslocational state. Binding of the next complementary nucleotide causes the
      formation of a stable dead-end complex in the posttranslocational state, which
      blocks the excision reaction. To provide mechanistic insight into the excision of
      the acyclic phosphonate nucleotide analog tenofovir, we compared the efficiencies
      of the reaction in response to changes in the translocation status of the enzyme.
      We found that rates of excision of tenofovir with wild-type reverse transcriptase
      can be as high as those seen with 3'-azido-3'-deoxythymidine monophosphate (AZT
      MP). Thymidine-associated mutations, which confer >100-fold and 3-fold decreased
      susceptibility to AZT and tenofovir, respectively, caused substantial increases
      in the efficiency of excision of both inhibitors. However, in contrast to the
      case for AZT-MP, the removal of tenofovir was highly sensitive to dead-end
      complex formation. Site-specific footprinting experiments revealed that complexes
      with AZT-terminated primers exist predominantly pretranslocation. In contrast,
      complexes with tenofovir-terminated primers are seen in both configurations. Low
      concentrations of the next nucleotide are sufficient to trap the complex
      posttranslocation despite the flexible, acyclic character of the compound. Thus,
      the relatively high rate of excision of tenofovir is partially neutralized by the
      facile switch to the posttranslocational state and by dead-end complex formation,
      which provides a degree of protection from excision in the cellular environment.

PMID- 17517853
TI  - Effect of rosiglitazone on the risk of myocardial infarction and death from
      cardiovascular causes.
AB  - BACKGROUND: Rosiglitazone is widely used to treat patients with type 2 diabetes
      mellitus, but its effect on cardiovascular morbidity and mortality has not been
      determined. METHODS: We conducted searches of the published literature, the Web
      site of the Food and Drug Administration, and a clinical-trials registry
      maintained by the drug manufacturer (GlaxoSmithKline). Criteria for inclusion in
      our meta-analysis included a study duration of more than 24 weeks, the use of a
      randomized control group not receiving rosiglitazone, and the availability of
      outcome data for myocardial infarction and death from cardiovascular causes. Of
      116 potentially relevant studies, 42 trials met the inclusion criteria. We
      tabulated all occurrences of myocardial infarction and death from cardiovascular
      causes. RESULTS: Data were combined by means of a fixed-effects model. In the 42
      trials, the mean age of the subjects was approximately 56 years, and the mean
      baseline glycated hemoglobin level was approximately 8.2%. In the rosiglitazone
      group, as compared with the control group, the odds ratio for myocardial
      infarction was 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03), and the
      odds ratio for death from cardiovascular causes was 1.64 (95% CI, 0.98 to 2.74;
      P=0.06). CONCLUSIONS: Rosiglitazone was associated with a significant increase in
      the risk of myocardial infarction and with an increase in the risk of death from
      cardiovascular causes that had borderline significance. Our study was limited by
      a lack of access to original source data, which would have enabled time-to-event
      analysis. Despite these limitations, patients and providers should consider the
      potential for serious adverse cardiovascular effects of treatment with
      rosiglitazone for type 2 diabetes.

PMID- 17517854
TI  - Rosiglitazone and cardiovascular risk.

PMID- 17517855
TI  - Burch colposuspension versus fascial sling to reduce urinary stress incontinence.
AB  - BACKGROUND: Many surgical procedures are available for women with urinary stress
      incontinence, yet few randomized clinical trials have been conducted to provide a
      basis for treatment recommendations. METHODS: We performed a multicenter,
      randomized clinical trial comparing two procedures--the pubovaginal sling, using
      autologous rectus fascia, and the Burch colposuspension--among women with stress
      incontinence. Women were eligible for the study if they had predominant symptoms
      associated with the condition, a positive stress test, and urethral
      hypermobility. The primary outcomes were success in terms of overall urinary
      incontinence measures, which required a negative pad test, no urinary
      incontinence (as recorded in a 3-day diary), a negative cough and Valsalva stress
      test, no self-reported symptoms, and no retreatment for the condition, and
      success in terms of measures of stress incontinence specifically, which required
      only the latter three criteria. We also assessed postoperative urge incontinence,
      voiding dysfunction, and adverse events. RESULTS: A total of 655 women were
      randomly assigned to study groups: 326 to undergo the sling procedure and 329 to
      undergo the Burch procedure; 520 women (79%) completed the outcome assessment. At
      24 months, success rates were higher for women who underwent the sling procedure
      than for those who underwent the Burch procedure, for both the overall category
      of success (47% vs. 38%, P=0.01) and the category specific to stress incontinence
      (66% vs. 49%, P<0.001). However, more women who underwent the sling procedure had
      urinary tract infections, difficulty voiding, and postoperative urge
      incontinence. CONCLUSIONS: The autologous fascial sling results in a higher rate
      of successful treatment of stress incontinence but also greater morbidity than
      the Burch colposuspension. (ClinicalTrials.gov number, NCT00064662
      [ClinicalTrials.gov] .).

PMID- 17517856
TI  - Shades of dry--curing urinary stress incontinence.

PMID- 17517857
TI  - Recovery of cognitive and dynamic motor function following concussion.
AB  - OBJECTIVE: Neuropsychological testing has been advocated as an important tool of
      proper post-concussion management. Although these measures provide information
      that can be used in the decision of when to return an individual to previous
      levels of physical activity, they provide little data on motor performance
      following injury. The purpose of this investigation was to examine the
      relationship between measures of dynamic motor performance and neuropsychological
      function following concussion over the course of 28 days. METHODS: Participants
      completed two experimental protocols: gait stability and neuropsychological
      testing. The gait stability protocol measured whole-body centre of mass motion as
      subjects walked under conditions of divided and undivided attention.
      Neuropsychological testing consisted of a computerised battery of tests designed
      to assess memory, reaction time, processing speed and concussion symptoms.
      Correlation coefficients were computed between all neuropsychological and gait
      variables and comparisons of neuropsychological and gait stability post
      concussion recovery curves were assessed. RESULTS: Dynamic motor tasks, such as
      walking under varying conditions of attention, are complex and demanding
      undertakings, which require a longer recovery time following a concussion than
      cognitive measures. Little statistical relationship was found between the
      neuropsychological and gait variables, and the recovery curves of
      neuropsychological and gait domains were observed to be independent. CONCLUSIONS:
      In order to fully examine the effects of concussion and determine the optimal
      time for a safe return to activity, a multi-factorial approach, including both
      cognitive and motor tasks, should be employed.

PMID- 17517858
TI  - A continuous mental task decreases the physiological response to soccer-specific
      intermittent exercise.
AB  - BACKGROUND: Epidemiological findings of higher injury incidence during the latter
      stages of soccer match-play have been attributed to fatigue. OBJECTIVE: To
      examine the interaction of physical and cognitive responses during soccer
      specific intermittent exercise. METHOD: Ten semi-professional soccer players
      completed a 90-minute laboratory-based treadmill protocol replicating the
      activity profile of soccer match-play. Two separate trials were performed in
      randomised order, with and without the added stressor of a continuous grid-based
      vigilance task. The exercise task comprised six repetitions of a 15 minute
      activity profile, separated by a passive 15 minute half-time interval. The
      vigilance task required continual attention and sporadic target response within a
      letter grid. Physical response (RPE, heart rate, blood lactate, salivary
      cortisol) and cognitive performance (response time, response accuracy) were
      quantified at 15 minute intervals. RESULTS: Completing the exercise task with the
      vigilance task resulted in decreased physiological (heart rate, blood lactate)
      response. This may be attributed to externally directed attention, resulting in
      association with the cognitive task and subsequent dissociation from the physical
      effort. Response speed generally improved with exercise duration, while there was
      evidence of impaired accuracy in the early stages of the first half and the
      latter stages of the second half. CONCLUSION: The interaction of physical and
      mental work was not additive in nature. The mental task had a masking effect on
      the physical response. Performing physical exercise tasks without due regard for
      appropriate psychological stimuli may therefore overestimate the physiological
      response.

PMID- 17517859
TI  - Surface-exposed proteins of Ehrlichia chaffeensis.
AB  - The surface proteins of Ehrlichia chaffeensis provide an important interface for
      pathogen-host interactions. To investigate the surface proteins of E.
      chaffeensis, membrane-impermeable, cleavable Sulfo-NHS-SS-Biotin was used to
      label intact bacteria. The biotinylated bacterial surface proteins were isolated
      by streptavidin-agarose affinity purification. The affinity-captured proteins
      were separated by electrophoresis, and five relatively abundant protein bands
      containing immunoreactive proteins were subjected to capillary-liquid
      chromatography-nanospray tandem mass spectrometry analysis. Nineteen out of 22
      OMP-1/P28 family proteins, including P28 (which previously was shown to be
      surface exposed), were detected in E. chaffeensis cultured in human monocytic
      leukemia THP-1 cells. For the first time, with the exception of P28 and P28-1, 17
      OMP-1/P28 family proteins were demonstrated to be expressed at the protein level.
      The surface exposure of OMP-1A and OMP-1N was verified by immunofluorescence
      microscopy. OMP-1B was undetectable either by surface biotinylation or by Western
      blotting of the whole bacterial lysate, suggesting that it is not expressed by E.
      chaffeensis cultured in THP-1 cells. Additional E. chaffeensis surface proteins
      detected were OMP85, hypothetical protein ECH_0525 (here named Esp73),
      immunodominant surface protein gp47, and 11 other proteins. The identification of
      E. chaffeensis surface-exposed proteins provides novel insights into the E.
      chaffeensis surface and lays the foundation for rational studies on pathogen-host
      interactions and vaccine development.

PMID- 17517860
TI  - Multiple consecutive lavage samplings reveal greater burden of disease and
      provide direct access to the nontypeable Haemophilus influenzae biofilm in
      experimental otitis media.
AB  - The typically recovered quantity of nontypeable Haemophilus influenzae (NTHi)
      bacteria in an ex vivo middle ear (ME) aspirate from the chinchilla model of
      experimental otitis media is insufficient for direct analysis of gene expression
      by microarray or of lipopolysaccharide glycoforms by mass spectrometry. This
      prompted us to investigate a strategy of multiple consecutive lavage samplings to
      increase ex vivo bacterial recovery. As multiple consecutive lavage samples
      significantly increased the total number of bacterial CFU collected during
      nasopharyngeal colonization or ME infection, this led us to evaluate whether
      bacteria sequentially acquired from consecutive lavages were similar. Comparative
      observation of complete ex vivo sample series by microscopy initially revealed ME
      inflammatory fluid consisting solely of planktonic-phase NTHi. In contrast,
      subsequent lavage samplings of the same infected ear revealed the existence of
      bacteria in two additional growth states, filamentous and biofilm encased. Gene
      expression analysis of such ex vivo samples was in accord with different
      bacterial growth phases in sequential lavage specimens. The existence of
      morphologically distinct NTHi subpopulations with varying levels of gene
      expression indicates that the pooling of specimens requires caution until methods
      for their separation are developed. This study based on multiple consecutive
      lavages is consistent with prior reports that NTHi forms a biofilm in vivo,
      describes the means to directly acquire ex vivo biofilm samples without
      sacrificing the animal, and has broad applicability for a study of mucosal
      infections. Moreover, this approach revealed that the actual burden of bacteria
      in experimental otitis media is significantly greater than was previously
      reported. Such findings may have direct implications for antibiotic treatment and
      vaccine development against NTHi.

PMID- 17517861
TI  - Uropathogenic Escherichia coli outer membrane antigens expressed during urinary
      tract infection.
AB  - Uncomplicated urinary tract infection (UTI) caused by uropathogenic Escherichia
      coli (UPEC) represents a prevalent and potentially severe infectious disease. In
      this study, we describe the application of an immunoproteomics approach to
      vaccine development that has been used successfully to identify vaccine targets
      in other pathogenic bacteria. Outer membranes were isolated from pyelonephritis
      strain E. coli CFT073 cultured under conditions that mimic the urinary tract
      environment, including iron limitation, osmotic stress, human urine, and exposure
      to uroepithelial cells. To identify antigens that elicit a humoral response
      during experimental UTI, outer membrane proteins were separated by two
      dimensional gel electrophoresis and probed using pooled antisera from 20 CBA/J
      mice chronically infected with E. coli CFT073. In total, 23 outer membrane
      antigens, including a novel iron compound receptor, reacted with the antisera and
      were identified by mass spectrometry. These antigens also included proteins with
      known roles in UPEC pathogenesis, such as ChuA, IroN, IreA, Iha, IutA, and FliC.
      These data demonstrate that an antibody response is directed against these
      virulence-associated factors during UTI. We also show that the genes encoding
      ChuA, IroN, hypothetical protein c2482, and IutA are significantly more prevalent
      (P < 0.01) among UPEC strains than among fecal-commensal E. coli isolates. Thus,
      we suggest that the conserved outer membrane antigens identified in this study
      could be rational candidates for a UTI vaccine designed to elicit protective
      immunity against UPEC infection.

PMID- 17517862
TI  - Heterogeneity of a Campylobacter jejuni protein that is secreted through the
      flagellar filament.
AB  - Cj0859c, or FspA, is a small, acidic protein of Campylobacter jejuni that is
      expressed by a sigma(28) promoter. Analysis of the fspA gene in 41 isolates of C.
      jejuni revealed two overall variants of the predicted protein, FspA1 and FspA2.
      Secretion of FspA occurs in broth-grown bacteria and requires a minimum flagellar
      structure. The addition of recombinant FspA2, but not FspA1, to INT407 cells in
      vitro resulted in a rapid induction of apoptosis. These data define a novel C.
      jejuni virulence factor, and the observed heterogeneity among fspA alleles
      suggests alternate virulence potential among different strains.

PMID- 17517863
TI  - Cytolysin-dependent escape of the bacterium from the phagosome is required but
      not sufficient for induction of the Th1 immune response against Listeria
      monocytogenes infection: distinct role of Listeriolysin O determined by cytolysin
      gene replacement.
AB  - Listeria monocytogenes evades the antimicrobial mechanisms of macrophages by
      escaping from the phagosome into the cytosolic space via a unique cytolysin that
      targets the phagosomal membrane, listeriolysin O (LLO), encoded by hly. Gamma
      interferon (IFN-gamma), which is known to play a pivotal role in the induction of
      Th1-dependent protective immunity in mice, appears to be produced, depending on
      the bacterial virulence factor. To determine whether the LLO molecule (the major
      virulence factor of L. monocytogenes) is indispensable or the escape of bacteria
      from the phagosome is sufficient to induce IFN-gamma production, we first
      constructed an hly-deleted mutant of L. monocytogenes and then established
      isogenic L. monocytogenes mutants expressing LLO or ivanolysin O (ILO), encoded
      by ilo from Listeria ivanovii. LLO-expressing L. monocytogenes was highly capable
      of inducing IFN-gamma production and Listeria-specific protective immunity, while
      the hly-deleted mutant was not. In contrast, the level of IFN-gamma induced by
      ILO-expressing L. monocytogenes was significantly lower both in vitro and in
      vivo, despite the ability of this strain to escape the phagosome and the
      intracellular multiplication at a level equivalent to that of LLO-expressing L.
      monocytogenes. Only a negligible level of protective immunity was induced in mice
      against challenge with LLO- and ILO-expressing L. monocytogenes. These results
      clearly show that escape of the bacterium from the phagosome is a prerequisite
      but is not sufficient for the IFN-gamma-dependent Th1 response against L.
      monocytogenes, and some distinct molecular nature of LLO is indispensable for the
      final induction of IFN-gamma that is essentially required to generate a Th1
      dependent immune response.

PMID- 17517864
TI  - Biofilms protect Mycoplasma pulmonis cells from lytic effects of complement and
      gramicidin.
AB  - The length of the tandem repeat region of the Vsa protein of Mycoplasma pulmonis
      has previously been shown to modulate the susceptibility of mycoplasmas to
      killing by complement: cells that produce a short form of the Vsa protein are
      highly sensitive, and cells producing the long Vsa protein are resistant. In
      contrast to their differing susceptibilities to complement, the mycoplasmas were
      highly sensitive to gramicidin irrespective of the length of the Vsa protein
      produced. We show here that when encased within a biofilm, cells of M. pulmonis
      producing a short form of the Vsa protein were more resistant to complement and
      gramicidin than mycoplasmas that were dispersed. The resistance appeared to be
      localized to those mycoplasmas within tower structures of the biofilms. Biofilm
      formation may be a mechanism that protects mycoplasmas from host immunity.

PMID- 17517865
TI  - Toll-like receptor 2-mediated signaling requirements for Francisella tularensis
      live vaccine strain infection of murine macrophages.
AB  - Francisella tularensis, an aerobic, non-spore-forming, gram-negative
      coccobacillus, is the causative agent of tularemia. We reported previously that
      F. tularensis live vaccine strain (LVS) elicited strong, dose-dependent NF-kappaB
      reporter activity in Toll-like receptor 2 (TLR2)-expressing HEK293T cells and
      proinflammatory gene expression in primary murine macrophages. Herein, we report
      that F. tularensis LVS-induced murine macrophage proinflammatory cytokine gene
      and protein expression are overwhelmingly TLR2 dependent, as evidenced by the
      abrogated responses of TLR2(-/-) macrophages. F. tularensis LVS infection also
      increased expression of TLR2 both in vitro, in mouse macrophages, and in vivo, in
      livers from F. tularensis LVS-infected mice. Colocalization of intracellular F.
      tularensis LVS, TLR2, and MyD88 was visualized by confocal microscopy. Signaling
      was abrogated if the F. tularensis LVS organisms were heat or formalin killed or
      treated with chloramphenicol, indicating that the TLR2 agonist activity is
      dependent on new bacterial protein synthesis. F. tularensis LVS replicates in
      macrophages; however, bacterial replication was not required for TLR2 signaling
      because LVSDeltaguaA, an F. tularensis LVS guanine auxotroph that fails to
      replicate in the absence of exogenous guanine, activated NF-kappaB in TLR2
      transfected HEK293T cells and induced cytokine expression in wild-type
      macrophages comparably to wild-type F. tularensis LVS. Collectively, these data
      indicate that the primary macrophage response to F. tularensis LVS is
      overwhelmingly TLR2 dependent, requires de novo bacterial protein synthesis, and
      is independent of intracellular F. tularensis replication.

PMID- 17517866
TI  - The Pseudomonas aeruginosa LasB metalloproteinase regulates the human urokinase
      type plasminogen activator receptor through domain-specific endoproteolysis.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen in human lungs, where its
      secretable LasB metalloproteinase can be a virulence factor. The urokinase-type
      plasminogen activator receptor (uPAR) participates in pericellular proteolysis
      and the adherence/migration of epithelial cells and leukocytes recruited during
      infection and shows functional regulation by various proteinases via limited
      endoproteolysis occurring within its three domains (D1 to D3). We thus examined
      the proteolytic activity of LasB on uPAR by using recombinant uPAR as well as
      uPAR-expressing, human monocytic, and bronchial epithelial cell lines. Protein
      immunoblotting and flow immunocytometry using a panel of domain-specific anti
      uPAR antibodies showed that LasB is able to cleave uPAR both within the sequence
      linking D1 to D2 and at the carboxy terminus of D3. Comparison of LasB-producing
      and LasB-deficient bacterial strains indicated that LasB is entirely responsible
      for the uPAR cleavage ability of P. aeruginosa. Based on amino-terminal protein
      microsequencing and mass spectrometry analysis of the cleavage of peptides
      mimicking the uPAR sequences targeted by LasB, cleavage sites were determined to
      be Ala(84)-Val(85) and Thr(86)-Tyr(87) (D1-D2) and Gln(279)-Tyr(280) (D3). Such a
      dual cleavage of uPAR led to the removal of amino-terminal D1, the generation of
      a truncated D2D3 species, and the shedding of D2D3 from cells. This proteolytic
      processing of uPAR was found to (i) drastically reduce the capacity of cells to
      bind urokinase and (ii) abrogate the interaction between uPAR and the matrix
      adhesive protein vitronectin. The LasB proteinase is thus endowed with a high
      potential for the alteration of uPAR expression and functioning on inflammatory
      cells during infections by P. aeruginosa.

PMID- 17517867
TI  - Periodontal bacterial DNA suppresses the immune response to mutans streptococcal
      glucosyltransferase.
AB  - Certain CpG motifs found in bacterial DNA enhance immune responses through Toll
      like receptor 9 (TLR-9) and may also demonstrate adjuvant properties. Our
      objective was to determine if DNA from bacteria associated with periodontal
      disease could affect the immune response to other bacterial antigens in the oral
      cavity. Streptococcus sobrinus glucosyltransferase (GTF), an enzyme involved in
      dental caries pathogenesis, was used as a test antigen. Rowett rats were injected
      with aluminum hydroxide (alum) with buffer, alum-GTF, or alum-GTF together with
      either Escherichia coli DNA, Fusobacterium nucleatum DNA, or Porphyromonas
      gingivalis DNA. Contrary to expectation, animals receiving alum-GTF plus
      bacterial DNA (P. gingivalis in particular) demonstrated significantly reduced
      serum immunoglobulin G (IgG) antibody, salivary IgA antibody, and T-cell
      proliferation to GTF compared to animals immunized with alum-GTF alone. A
      diminished antibody response was also observed after administration of alum-GTF
      with the P. gingivalis DNA either together or separately, indicating that
      physical complexing of antigen and DNA was not responsible for the reduction in
      antibody. Since TLR triggering by DNA induces synthesis of prospective
      suppressive factors (e.g., suppressor of cytokine signaling [SOCS]), the effects
      of P. gingivalis DNA and GTF exposure on rat splenocyte production of SOCS family
      molecules and inflammatory cytokines were investigated in vitro. P. gingivalis
      DNA significantly up-regulated SOCS1 and SOCS5 expression and down-regulated
      interleukin-10 expression by cultured splenocytes. These results suggested that
      DNA from periodontal disease-associated bacteria did not enhance, but in fact
      suppressed, the immune response to a protein antigen from cariogenic
      streptococci, potentially through suppressive SOCS components triggered by innate
      mechanisms.

PMID- 17517868
TI  - Cytokines, signaling pathways, and effector molecules required for the control of
      Leishmania (Viannia) braziliensis in mice.
AB  - Cutaneous leishmaniasis is caused by protozoan parasites of the genus Leishmania.
      The mechanisms of pathogen control have been established primarily in the mouse
      model of Leishmania major infection, but they might not hold true for other
      Leishmania species associated with cutaneous disease. Here, we analyzed the role
      of cytokines, signaling components, and effector molecules in the control of New
      World cutaneous leishmaniasis due to L. braziliensis. Unlike L. major, L.
      braziliensis caused small, nonulcerative, and self-healing skin swelling in
      C57BL/6 mice, as well as BALB/c mice. In contrast to the results obtained for L.
      mexicana, mice deficient for interleukin-12 or its key signaling molecule, signal
      transducer and activator of transcription 4, rapidly succumbed to severe visceral
      leishmaniasis. Infection of tumor necrosis factor knockout mice with L.
      braziliensis led to progressive, nonhealing skin lesions with erosions and
      hemorrhagic ulcerations, but in contrast to the results with L. major, only 20 to
      30% of the mice developed fatal visceral disease. As seen with L. major, mice
      with a deleted inducible nitric oxide synthase gene (iNOS(-/-)) were unable to
      contain L. braziliensis in the skin, whereas the control of the parasite in the
      spleen remained unimpaired. Unlike what happens in L. major infections, NADPH
      oxidase had no impact on the course of disease in L. braziliensis-infected mice.
      These results not only define essential components of a protective immune
      response to L. braziliensis but also illustrate that the requirements for the
      control of cutaneous leishmaniasis vary between different parasite species.

PMID- 17517869
TI  - Extracytoplasmic-stress-responsive pathways modulate type III secretion in
      Yersinia pseudotuberculosis.
AB  - Three signal transduction pathways, the two-component systems CpxRA and BaeSR and
      the alternative sigma factor sigma(E), respond to extracytoplasmic stress that
      facilitates bacterial adaptation to changing environments. At least the CpxRA and
      sigma(E) pathways control the production of protein-folding and degradation
      factors that counter the effects of protein misfolding in the periplasm. This
      function also influences the biogenesis of multicomponent extracellular
      appendages that span the bacterial envelope, such as various forms of pili.
      Herein, we investigated whether any of these regulatory pathways in the
      enteropathogen Yersinia pseudotuberculosis affect the functionality of the Ysc
      Yop type III secretion system. This is a multicomponent molecular syringe
      spanning the bacterial envelope used to inject effector proteins directly into
      eukaryotic cells. Disruption of individual components revealed that the Cpx and
      sigma(E) pathways are important for Y. pseudotuberculosis type III secretion of
      Yops (Yersinia outer proteins). In particular, a loss of CpxA, a sensor kinase,
      reduced levels of structural Ysc (Yersinia secretion) components in bacterial
      membranes, suggesting that these mutant bacteria are less able to assemble a
      functional secretion apparatus. Moreover, these bacteria were no longer capable
      of localizing Yops into the eukaryotic cell interior. In addition, a cpxA lcrQ
      double mutant engineered to overproduce and secrete Yops was still impaired in
      intoxicating cells. Thus, the Cpx pathway might mediate multiple influences on
      bacterium-target cell contact that modulate Yersinia type III secretion-dependent
      host cell cytotoxicity.

PMID- 17517870
TI  - The large clostridial toxins from Clostridium sordellii and C. difficile repress
      glucocorticoid receptor activity.
AB  - We have previously shown that Bacillus anthracis lethal toxin represses
      glucocorticoid receptor (GR) transactivation. We now report that repression of GR
      activity also occurs with the large clostridial toxins produced by Clostridium
      sordellii and C. difficile. This was demonstrated using a transient transfection
      assay system for GR transactivation. We also report that C. sordellii lethal
      toxin inhibited GR function in an ex vivo assay, where toxin reduced the
      dexamethasone suppression of the proinflammatory cytokine tumor necrosis factor
      alpha (TNF-alpha). Furthermore, the glucocorticoid antagonist RU-486 in
      combination with C. sordellii lethal toxin additively prevented glucocorticoid
      suppression of TNF-alpha. These findings corroborate the fact that GR is a target
      for the toxin and suggest a physiological role for toxin-associated GR repression
      in inflammation. Finally, we show that this repression is associated with toxins
      that inactivate p38 mitogen-activated protein kinase (MAPK).

PMID- 17517871
TI  - Plasmodium yoelii sporozoites with simultaneous deletion of P52 and P36 are
      completely attenuated and confer sterile immunity against infection.
AB  - Malaria infection starts when sporozoites are transmitted to the mammalian host
      during a mosquito bite. Sporozoites enter the blood circulation, reach the liver,
      and infect hepatocytes. The formation of a parasitophorous vacuole (PV)
      establishes their intracellular niche. Recently, two members of the 6-Cys domain
      protein family, P52 and P36, were each shown to play an important albeit
      nonessential role in Plasmodium berghei sporozoite infectivity for the rodent
      host. Here, we generated p52/p36-deficient Plasmodium yoelii parasites by the
      simultaneous deletion of both genes using a single genetic manipulation. p52/p36
      deficient parasites exhibited normal progression through the life cycle during
      blood-stage infection, transmission to mosquitoes, mosquito-stage development,
      and sporozoite infection of the salivary glands. p52/p36-deficient sporozoites
      also showed normal motility and cell traversal activity. However,
      immunofluorescence analysis and electron microscopic observations revealed that
      p52/p36-deficient parasites did not form a PV within hepatocytes in vitro and in
      vivo. The p52/p36-deficient parasites localized as free entities in the host cell
      cytoplasm or the host cell nucleoplasm and did not develop as liver stages.
      Consequently, they did not cause blood-stage infections even at high sporozoite
      inoculation doses. Mice immunized with p52/p36-deficient sporozoites were
      completely protected against infectious sporozoite challenge. Our results
      demonstrate for the first time the generation of two-locus gene deletion
      attenuated parasites that infect the liver but do not progress to blood-stage
      infection. The study will critically guide the design of Plasmodium falciparum
      live attenuated malaria vaccines.

PMID- 17517872
TI  - Mycolactone-mediated inhibition of tumor necrosis factor production by
      macrophages infected with Mycobacterium ulcerans has implications for the control
      of infection.
AB  - The pathogenicity of Mycobacterium ulcerans, the agent of Buruli ulcer, depends
      on the cytotoxic exotoxin mycolactone. Little is known about the immune response
      to this pathogen. Following the demonstration of an intracellular growth phase in
      the life cycle of M. ulcerans, we investigated the production of tumor necrosis
      factor (TNF) induced by intramacrophage bacilli of diverse toxigenesis/virulence,
      as well as the biological relevance of TNF during M. ulcerans experimental
      infections. Our data show that murine bone marrow-derived macrophages infected
      with mycolactone-negative strains of M. ulcerans (nonvirulent) produce high
      amounts of TNF, while macrophages infected with mycolactone-positive strains of
      intermediate or high virulence produce intermediate or low amounts of TNF,
      respectively. These results are in accordance with the finding that TNF receptor
      P55-deficient (TNF-P55 KO) mice are not more susceptible than wild-type mice to
      infection by the highly virulent strains but are more susceptible to nonvirulent
      and intermediately virulent strains, demonstrating that TNF is required to
      control the proliferation of these strains in animals experimentally infected by
      M. ulcerans. We also show that mycolactone produced by intramacrophage M.
      ulcerans bacilli inhibits, in a dose-dependent manner, but does not abrogate, the
      production of macrophage inflammatory protein 2, which is consistent with the
      persistent inflammatory responses observed in experimentally infected mice.

PMID- 17517873
TI  - Opa proteins of pathogenic neisseriae initiate Src kinase-dependent or lipid raft
      mediated uptake via distinct human carcinoembryonic antigen-related cell adhesion
      molecule isoforms.
AB  - Several pathogenic bacteria exploit human carcinoembryonic antigen-related cell
      adhesion molecules (CEACAMs) for adhesion to and invasion into their host cells.
      CEACAM isoforms have characteristic expression patterns on epithelial,
      endothelial, or hematopoietic cells, providing bacteria with distinct sets of
      receptors on particular tissues. For example, while CEACAM1 and CEACAM6 have a
      wide tissue distribution, CEACAM3, CEACAM4, and CEACAM8 are uniquely expressed on
      primary human granulocytes, whereas CEA and CEACAM7 are limited to epithelia. By
      reconstitution of a CEACAM-deficient cell line with individual CEACAMs, we have
      analyzed the requirements for CEACAM-mediated internalization of Neisseria
      gonorrhoeae. Our results point to two mechanistically different uptake pathways
      triggered by either epithelial CEACAMs (CEACAM1, CEA, and CEACAM6) or the
      granulocyte-specific CEACAM3. In particular, CEACAM3-mediated uptake critically
      depends on Src family protein tyrosine kinase (PTK) activity, and CEACAM3
      associates with the SH2 domains of several Src PTKs. In contrast, epithelial
      CEACAMs require the integrity of cholesterol-rich membrane microdomains and are
      affected by cholesterol depletion, whereas CEACAM3-mediated uptake by transfected
      cells or the opsonin-independent phagocytosis by human granulocytes is not
      altered in the presence of cholesterol chelators. These results allow the
      subdivision of all human CEACAMs known to be utilized as pathogen receptors into
      functional groups and point to important consequences for bacterial engagement of
      distinct CEACAM isoforms.

PMID- 17517874
TI  - Exogenous farnesol interferes with the normal progression of cytokine expression
      during candidiasis in a mouse model.
AB  - Candida albicans, a dimorphic fungus composed of yeast and mycelial forms, is the
      most common human fungal pathogen. Th1 cytokines such as interleukin-2 (IL-2),
      gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), which
      are induced by macrophage IL-12, are critical to resistance against systemic
      candidiasis, while Th2 cytokines such as IL-4 and IL-5 are less critical.
      Farnesol is a quorum-sensing molecule produced by C. albicans that controls the
      formation of mycelia but is also a virulence factor. To determine whether
      farnesol enhances the virulence of C. albicans by modulating the production of
      Th1 and Th2 cytokines, mice were pretreated with farnesol prior to intravenous
      infection with a sublethal dose of farnesol-producing C. albicans. Production of
      IL-2, IL-4, IL-5, TNF-alpha, IFN-gamma, and IL-12 was evaluated by bead-array
      flow cytometry and enzyme-linked immunosorbent assay. Mice exhibited an elevation
      in serum TNF-alpha levels at 48 h and an elevation in IFN-gamma and IL-12 levels
      at 6 to 12 h after infection with C. albicans. Pretreatment with farnesol
      significantly reduced the elevation of both IFN-gamma and IL-12 but not TNF
      alpha. In contrast, mice pretreated with farnesol exhibited an unexpected
      elevation in IL-5 levels. To determine whether farnesol has a direct effect on
      macrophage production of IL-12, peritoneal macrophages were pretreated with
      farnesol prior to stimulation with IFN-gamma plus lipopolysaccharide (LPS).
      Farnesol inhibited production of both IL-12 p40 and p70 from IFN-gamma/LPS
      stimulated macrophages. Therefore, the role of farnesol in systemic candidiasis
      is likely due to its ability to inhibit the critical Th1 cytokines IFN-gamma and
      IL-12 and perhaps to enhance a Th2 cytokine, IL-5.

PMID- 17517875
TI  - Helicobacter pylori chemotaxis modulates inflammation and bacterium-gastric
      epithelium interactions in infected mice.
AB  - The ulcer-causing pathogen Helicobacter pylori uses directed motility, or
      chemotaxis, to both colonize the stomach and promote disease development.
      Previous work showed that mutants lacking the TlpB chemoreceptor, one of the
      receptors predicted to drive chemotaxis, led to less inflammation in the gerbil
      stomach than did the wild type. Here we expanded these findings and examined the
      effects on inflammation of completely nonchemotactic mutants and mutants lacking
      each chemoreceptor. Of note, all mutants colonized mice to the same levels as did
      wild-type H. pylori. Infection by completely nonchemotactic mutants (cheW or
      cheY) resulted in significantly less inflammation after both 3 and 6 months of
      infection. Mutants lacking either the TlpA or TlpB H. pylori chemotaxis receptors
      also had alterations in inflammation severity, while mutants lacking either of
      the other two chemoreceptors (TlpC and HylB) behaved like the wild type. Fully
      nonchemotactic and chemoreceptor mutants adhered to cultured gastric epithelial
      cells and caused cellular release of the chemokine interleukin-8 in vitro similar
      to the release caused by the wild type. The situation appeared to be different in
      the stomach. Using silver-stained histological sections, we found that
      nonchemotactic cheY or cheW mutants were less likely than the wild type to be
      intimately associated with the cells of the gastric mucosa, although there was
      not a strict correlation between intimate association and inflammation. Because
      others have shown that in vivo adherence promotes inflammation, we propose a
      model in which H. pylori uses chemotaxis to guide it to a productive interaction
      with the stomach epithelium.

PMID- 17517876
TI  - Endogenous interleukin-18 improves the early antimicrobial host response in
      severe melioidosis.
AB  - Melioidosis is caused by the soil saprophyte Burkholderia pseudomallei and is
      endemic in Southeast Asia. The pathogenesis of melioidosis is still largely
      unknown, although gamma interferon (IFN-gamma) seems to play an obligatory role
      in host defense. Previously, we have shown that IFN-gamma production in
      melioidosis is controlled in part by interleukin-18 (IL-18). The aim of the
      present study was to determine the role of IL-18 in the immune response to B.
      pseudomallei. For this the following investigations were performed. (i) Plasma IL
      18 and blood monocyte IL-18 mRNA levels were elevated in 34 patients with culture
      proven melioidosis compared to the levels in 32 local healthy controls; in
      addition, IL-18 binding protein levels were markedly elevated in patients,
      strongly correlating with mortality. (ii) IL-18 gene-deficient (IL-18 knockout
      [KO]) mice showed accelerated mortality after intranasal infection with a lethal
      dose of B. pseudomallei, which was accompanied by enhanced bacterial growth in
      their lungs, livers, spleens, kidneys, and blood at 24 and 48 h postinfection,
      compared to wild-type mice. In addition, IL-18 KO mice displayed evidence of
      enhanced hepatocellular injury and renal insufficiency. Together, these data
      indicate that the enhanced production of IL-18 in melioidosis is an essential
      part of a protective immune response to this severe infection.

PMID- 17517877
TI  - Identification of a LolC homologue in Burkholderia pseudomallei, a novel
      protective antigen for melioidosis.
AB  - Melioidosis is an emerging disease of humans in Southeast Asia and tropical
      Australia. The bacterium causing this disease, Burkholderia pseudomallei, is also
      considered a bioterrorism agent, and as yet there is no licensed vaccine for
      preventing B. pseudomallei infection. In this study, we evaluated selected
      proteins (LolC, PotF, and OppA) of the ATP-binding cassette systems of B.
      pseudomallei as candidate vaccine antigens. Nonmembrane regions of the B.
      pseudomallei proteins were expressed and purified from Escherichia coli and then
      evaluated as vaccine candidates in an established mouse model of B. pseudomallei
      infection. When delivered with the monophosphoryl lipid A-trehalose
      dicorynomycolate adjuvant, the proteins stimulated antigen-specific humoral and
      cellular immune responses. Immunization with LolC or PotF protein domains
      afforded significant protection against a subsequent challenge with B.
      pseudomallei. The most promising vaccine candidate, LolC, provided a greater
      level of protection when it was administered with immune-stimulating complexes
      complexed with CpG oligodeoxynucleotide 10103. Immunization with LolC also
      protected against a subsequent challenge with a heterologous strain of B.
      pseudomallei, demonstrating the potential utility of this protein as a vaccine
      antigen for melioidosis.

PMID- 17517878
TI  - Human lung innate immune response to Bacillus anthracis spore infection.
AB  - Bacillus anthracis, the causative agent of inhalational anthrax, enters a host
      through the pulmonary system before dissemination. We have previously shown that
      human alveolar macrophages participate in the initial innate immune response to
      B. anthracis spores through cell signal-mediated cytokine release. We proposed
      that the lung epithelia also participate in the innate immune response to this
      pathogen, and we have developed a human lung slice model to study this process.
      Exposure of our model to B. anthracis (Sterne) spores rapidly activated the
      mitogen-activated protein kinase signaling pathways ERK, p38, and JNK. In
      addition, an RNase protection assay showed induction of mRNA of several cytokines
      and chemokines. This finding was reflected at the translational level by protein
      peak increases of 3-, 25-, 9-, 34-, and 5-fold for interleukin-6 (IL-6), tumor
      necrosis factor alpha, IL-8, macrophage inflammatory protein 1alpha/beta, and
      monocyte chemoattractant protein 1, respectively, as determined by an enzyme
      linked immunosorbent assay. Inhibition of individual pathways by UO126, SP600125,
      and SB0203580 decreased induction of chemokines and cytokines by spores, but this
      depended on the pathways inhibited and the cytokines and chemokines induced.
      Combining all three inhibitors reduced induction of all cytokines and chemokines
      tested to background levels. An immunohistochemistry analysis of IL-6 and IL-8
      revealed that alveolar epithelial cells and macrophages and a few interstitial
      cells are the source of the cytokines and chemokines. Taken together, these data
      showed the activation of the pulmonary epithelium in response to B. anthracis
      spore exposure. Thus, the lung epithelia actively participate in the innate
      immune response to B. anthracis infection through cell signal-mediated
      elaboration of cytokines and chemokines.

PMID- 17517879
TI  - Pasteurella multocida expresses two lipopolysaccharide glycoforms simultaneously,
      but only a single form is required for virulence: identification of two acceptor
      specific heptosyl I transferases.
AB  - Lipopolysaccharide (LPS) is a critical virulence determinant in Pasteurella
      multocida and a major antigen responsible for host protective immunity. In other
      mucosal pathogens, variation in LPS or lipooligosaccharide structure typically
      occurs in the outer core oligosaccharide regions due to phase variation. P.
      multocida elaborates a conserved oligosaccharide extension attached to two
      different, simultaneously expressed inner core structures, one containing a
      single phosphorylated 3-deoxy-D-manno-octulosonic acid (Kdo) residue and the
      other containing two Kdo residues. We demonstrate that two heptosyltransferases,
      HptA and HptB, add the first heptose molecule to the Kdo(1) residue and that each
      exclusively recognizes different acceptor molecules. HptA is specific for the
      glycoform containing a single, phosphorylated Kdo residue (glycoform A), while
      HptB is specific for the glycoform containing two Kdo residues (glycoform B). In
      addition, KdkA was identified as a Kdo kinase, required for phosphorylation of
      the first Kdo molecule. Importantly, virulence data obtained from infected
      chickens showed that while wild-type P. multocida expresses both LPS glycoforms
      in vivo, bacterial mutants that produced only glycoform B were fully virulent,
      demonstrating for the first time that expression of a single LPS form is
      sufficient for P. multocida survival in vivo. We conclude that the ability of P.
      multocida to elaborate alternative inner core LPS structures is due to the
      simultaneous expression of two different heptosyltransferases that add the first
      heptose residue to the nascent LPS molecule and to the expression of both a
      bifunctional Kdo transferase and a Kdo kinase, which results in the initial
      assembly of two inner core structures.

PMID- 17517881
TI  - Pathogen specificity and autoimmunity are distinct features of antigen-driven
      immune responses in neuroborreliosis.
AB  - Neuroborreliosis (NB) is a chronic infectious disease of the central nervous
      system (CNS) caused by a tick-borne spirochete, Borrelia burgdorferi. In addition
      to direct effects of the causative infectious agent, additional immunity-mediated
      mechanisms are thought to play a role in the CNS pathology of NB. In order to
      further understand the involvement of humoral immune mechanisms in NB, we
      dissected the intrathecal antibody responses down to the single-plasma-cell
      level. Starting with single-cell reverse transcription-PCR of fluorescence
      activated cell sorter-sorted cerebrospinal fluid plasma cells from an NB patient,
      we identified expanded clones and resurrected the antigen specificity of their
      secreted antibodies through recombinant expression of the correctly paired
      immunoglobulin heavy- and light-chain genes as monoclonal antibodies (MAbs). As
      expected, we found specificity for the causative infectious agent, B.
      burgdorferi, among the clonally expanded plasma cell (cePC)-derived MAbs.
      However, from an independent cePC of the same patient, we could derive MAbs
      specific for human CNS myelin, without detectable cross-reactivity with B.
      burgdorferi antigens. While reactivity against B. burgdorferi is a known feature
      of humoral immune responses in NB, we show (i) that immune responses specific for
      self antigens may be a distinct feature of CNS infections independent of pathogen
      reactivity and (ii) that humoral autoimmunity in NB (since found in cePC) is the
      result of a truly antigen-driven immune response. Our findings indicate that in
      NB mechanisms may be at play that induce distinct immune responses specific for
      pathogen and self antigens independent from "molecular mimicry."

PMID- 17517880
TI  - Clostridium difficile toxins A and B directly stimulate human mast cells.
AB  - Clostridium difficile toxins A and B (TcdA and TcdB) are the causative agents of
      antibiotic-associated pseudomembranous colitis. Mucosal mast cells play a crucial
      role in the inflammatory processes underlying this disease. We studied the direct
      effects of TcdA and TcdB on the human mast cell line HMC-1 with respect to
      degranulation, cytokine release, and the activation of proinflammatory signal
      pathways. TcdA and TcdB inactivate Rho GTPases, the master regulators of the
      actin cytoskeleton. The inactivation of Rho GTPases induced a reorganization of
      the actin cytoskeleton accompanied by morphological changes of cells. The TcdB
      induced reorganization of the actin cytoskeleton in HMC-1 cells reduced the
      number of electron-dense mast cell-specific granules. Accordingly, TcdB induced
      the release of hexosaminidase, a marker for degranulation, in HMC-1 cells. The
      actin rearrangement was found to be responsible for degranulation since
      latrunculin B induced a comparable hexosaminidase release. In addition, TcdB as
      well as latrunculin B induced the activation of p38 mitogen-activated protein
      kinase (MAPK) and extracellular signal-regulated kinase 1/2 and also resulted in
      a p38 MAPK-dependent increased formation of prostaglandins D(2) and E(2). The
      autocrine stimulation of HMC-1 cells by prostaglandins partially contributed to
      the degranulation. Interestingly, TcdB-treated HMC-1 cells, but not latrunculin B
      treated HMC-1 cells, showed a strong p38 MAPK-dependent increase in interleukin-8
      release. Differences in the mast cell responses to TcdB and latrunculin B are
      probably due to the presence of functionally inactive Rho GTPases in toxin
      treated cells. Thus, the HMC-1 cell line is a promising model for studying the
      direct effects of C. difficile toxins on mast cells independently of the tissue
      context.

PMID- 17517882
TI  - Role of laminin terminal globular domains in basement membrane assembly.
AB  - Laminins contribute to basement membrane assembly through interactions of their N
      and C-terminal globular domains. To further analyze this process, recombinant
      laminin-111 heterotrimers with deletions and point mutations were generated by
      recombinant expression and evaluated for their ability to self-assemble, interact
      with nidogen-1 and type IV collagen, and form extracellular matrices on cultured
      Schwann cells by immunofluorescence and electron microscopy. Wild-type laminin
      and laminin without LG domains polymerized in contrast to laminins with deleted
      alpha1-, beta1-, or gamma1-LN domains or with duplicated beta1- or alpha1-LN
      domains. Laminins with a full complement of LN and LG domains accumulated on cell
      surfaces substantially above those lacking either LN or LG domains and formed a
      lamina densa. Accumulation of type IV collagen onto the cell surface was found to
      require laminin with separate contributions arising from the presence of laminin
      LN domains, nidogen-1, and the nidogen-binding site in laminin. Collectively, the
      data support the hypothesis that basement membrane assembly depends on laminin
      self-assembly through formation of alpha-, beta-, and gamma-LN domain complexes
      and LG-mediated cell surface anchorage. Furthermore, type IV collagen recruitment
      into the laminin extracellular matrices appears to be mediated through a nidogen
      bridge with a lesser contribution arising from a direct interaction with laminin.

PMID- 17517883
TI  - The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of
      mammalian target of rapamycin complex 1.
AB  - The proline-rich Akt substrate of 40 kilodaltons (PRAS40) was identified as a
      raptor-binding protein that is phosphorylated directly by mammalian target of
      rapamycin (mTOR) complex 1 (mTORC1) but not mTORC2 in vitro, predominantly at
      PRAS40 (Ser(183)). The binding of S6K1 and 4E-BP1 to raptor requires a TOR
      signaling (TOS) motif, which contains an essential Phe followed by four
      alternating acidic and small hydrophobic amino acids. PRAS40 binding to raptor
      was severely inhibited by mutation of PRAS40 (Phe(129) to Ala). Immediately
      carboxyl-terminal to Phe(129) are two small hydrophobic amino acid followed by
      two acidic residues. PRAS40 binding to raptor was also abolished by mutation of
      the major mTORC1 phosphorylation site, Ser(183), to Asp. PRAS40 (Ser(183)) was
      phosphorylated in intact cells; this phosphorylation was inhibited by rapamycin,
      by 2-deoxyglucose, and by overexpression of the tuberous sclerosis complex
      heterodimer. PRAS40 (Ser(183)) phosphorylation was also inhibited reversibly by
      withdrawal of all or of only the branched chain amino acids; this inhibition was
      reversed by overexpression of the Rheb GTPase. Overexpressed PRAS40 suppressed
      the phosphorylation of S6K1 and 4E-BP1 at their rapamycin-sensitive
      phosphorylation sites, and reciprocally, overexpression of S6K1 or 4E-BP1
      suppressed phosphorylation of PRAS40 (Ser(183)) and its binding to raptor. RNA
      interference-induced depletion of PRAS40 enhanced the amino acid-stimulated
      phosphorylation of both S6K1 and 4E-BP1. These results establish PRAS40 as a
      physiological mTORC1 substrate that contains a variant TOS motif. Moreover, they
      indicate that the ability of raptor to bind endogenous substrates is limiting for
      the activity of mTORC1 in vivo and is therefore a potential locus of regulation.

PMID- 17517884
TI  - Sustained hydrogen peroxide induces iron uptake by transferrin receptor-1
      independent of the iron regulatory protein/iron-responsive element network.
AB  - Local and systemic inflammatory conditions are characterized by the intracellular
      deposition of excess iron, which may promote tissue damage via Fenton chemistry.
      Because the Fenton reactant H(2)O(2) is continuously released by inflammatory
      cells, a tight regulation of iron homeostasis is required. Here, we show that
      exposure of cultured cells to sustained low levels of H(2)O(2) that mimic its
      release by inflammatory cells leads to up-regulation of transferrin receptor 1
      (TfR1), the major iron uptake protein. The increase in TfR1 results in increased
      transferrin-mediated iron uptake and cellular accumulation of the metal. Although
      iron regulatory protein 1 is transiently activated by H(2)O(2), this response is
      not sufficient to stabilize TfR1 mRNA and to repress the synthesis of the iron
      storage protein ferritin. The induction of TfR1 is also independent of
      transcriptional activation via hypoxia-inducible factor 1alpha or significant
      protein stabilization. In contrast, pulse experiments with (35)S-labeled
      methionine/cysteine revealed an increased rate of TfR1 synthesis in cells exposed
      to sustained low H(2)O(2) levels. Our results suggest a novel mechanism of iron
      accumulation by sustained H(2)O(2), based on the translational activation of
      TfR1, which could provide an important (patho) physiological link between iron
      metabolism and inflammation.

PMID- 17517885
TI  - Skp1-Cullin-F-box-dependent degradation of Aah1p requires its interaction with
      the F-box protein Saf1p.
AB  - When yeast cells enter into quiescence in response to nutrient limitation, the
      adenine deaminase Aah1p is specifically degraded via a process requiring the F
      box protein Saf1p and components of the Skp1-Cullin-F-box complex. In this paper,
      we show that Saf1p interacts with both Aah1p and Skp1p. Interaction with Skp1p,
      but not with Aah1p, requires the F-box domain of Saf1p. Based on deletion and
      point mutations, we further demonstrate that the F-box domain of Saf1p is
      critical for degradation of Aah1p. We also establish that overexpression of Saf1p
      in proliferating cells is sufficient to trigger the degradation of Aah1p. Using
      this property and a two-dimensional protein gel approach, we found that Saf1p has
      a small number of direct targets. Finally, we isolated and characterized several
      point mutations in Aah1p, which increase its stability during quiescence. The
      majority of the mutated residues are located in two distinct exposed regions in
      the Aah1p three-dimensional model structure. Two hybrid experiments strongly
      suggest that these domains are directly involved in interaction with Saf1p.
      Importantly, we obtained a mutation in Aah1p that does not affect the protein
      interaction with Saf1p but abolishes Aah1p degradation. Because this mutated
      residue is an exposed lysine in the Aah1p three-dimensional model, we propose
      that it is likely to be a major ubiquitylation site. All together, our data
      strongly argue for Saf1p being a bona fide Skp1-Cullin-F-box subunit.

PMID- 17517886
TI  - Functional characterization of AtATM1, AtATM2, and AtATM3, a subfamily of
      Arabidopsis half-molecule ATP-binding cassette transporters implicated in iron
      homeostasis.
AB  - The functional capabilities of one of the smallest subfamilies of ATP-binding
      cassette transporters from Arabidopsis thaliana, the AtATMs, are described.
      Designated AtATM1, AtAATM2, and AtATM3, these half-molecule ABC proteins are
      homologous to the yeast mitochondrial membrane protein ATM1 (ScATM1), which is
      clearly implicated in the export of mitochondrially synthesized iron/sulfur
      clusters. Yeast ATM1-deficient (atm1) mutants grow very slowly (have a petite
      phenotype), are respiration-deficient, accumulate toxic levels of iron in their
      mitochondria, and show enhanced compensatory high affinity iron uptake. Of the
      three Arabidopsis ATMs, AtATM3 bears the closest functional resemblance to
      ScATM1. Heterologously expressed AtATM3 is not only able to complement the yeast
      atm1 petite phenotype but is also able to suppress the constitutively high
      capacity for high affinity iron uptake associated with loss of the chromosomal
      copy of ScATM1, abrogate intra-mitochondrial iron hyperaccumulation, and restore
      mitochondrial respiratory function and cytochrome c levels. By comparison, AtATM1
      only weakly suppresses the atm1 phenotype, and AtATM2 exerts little or no
      suppressive action but instead is toxic when expressed in this system. The
      differences between AtATM3 and AtATM1 are maintained after exchanging their
      target peptides, and these proteins as well as AtATM2 colocalize with the
      mitochondrial fluor MitoTracker Red when expressed in yeast as GFP fusions.
      Although its toxicity when heterologously expressed in yeast, except when fused
      with GFP, precludes the functional analysis of native AtATM2, a common function,
      mitochondrial export of Fe/S clusters or their precursors for the assembly of
      cytosolic Fe/S proteins, is inferred for AtATM3 and AtATM1.

PMID- 17517887
TI  - A ubiquitin-binding motif in the translesion DNA polymerase Rev1 mediates its
      essential functional interaction with ubiquitinated proliferating cell nuclear
      antigen in response to DNA damage.
AB  - During normal DNA replication, the proliferating cell nuclear antigen (PCNA)
      enhances the processivity of DNA polymerases at the replication fork. When DNA
      damage is encountered, PCNA is monoubiquitinated on Lys-164 by the Rad6-Rad18
      complex as the initiating step of translesion synthesis. DNA damage bypass by the
      translesion synthesis polymerase Rev1 is enhanced by the presence of
      ubiquitinated PCNA. Here we have carried out a mutational analysis of Rev1, and
      we have identified the functional domain in the C terminus of Rev1 that mediates
      interactions with PCNA. We show that a unique motif within this domain binds the
      ubiquitin moiety of ubiquitinated PCNA. Point mutations within this ubiquitin
      binding motif of Rev1 (L821A,P822A,I825A) abolish its functional interaction with
      ubiquitinated PCNA in vitro and strongly attenuate damage-induced mutagenesis in
      vivo. Taken together, these studies suggest a specific mechanism by which the
      interaction between Rev1 and ubiquitinated PCNA is stabilized during the DNA
      damage response.

PMID- 17517888
TI  - Akt-mediated liver growth promotes induction of cyclin E through a novel
      translational mechanism and a p21-mediated cell cycle arrest.
AB  - The control of hepatocyte growth is relevant to the processes of liver
      regeneration, development, metabolic homeostasis, and cancer. A key component of
      growth control is the protein kinase Akt, which acts downstream of mitogens and
      nutrients to affect protein translation and cell cycle progression. In this
      study, we found that transient transfection of activated Akt triggered a 3-4-fold
      increase in liver size within days but only minimal hepatocyte proliferation. Akt
      induced liver growth was associated with marked up-regulation of cyclin E but not
      cyclin D1. Analysis of liver polyribosomes demonstrated that the post
      transcriptional induction of cyclin E was associated with increased translational
      efficiency of this mRNA, suggesting that cell growth promotes expression of this
      protein through a translational mechanism that is distinct from the cyclin D-E2F
      pathway. Treatment of Akt-transfected mice with rapamycin only partially
      inhibited liver growth and did not prevent the induction of cyclin E protein,
      indicating that target of rapamycin activity is not necessary for this response.
      In the enlarged livers, cyclin E-Cdk2 complexes were present in high abundance
      but were inactive due to increased binding of p21 to these complexes. Akt
      transfection of p21(-/-) mice promoted liver growth, activation of Cdk2, and
      enhanced hepatocyte proliferation. In conclusion, growth promotes cyclin E
      expression through a novel translational mechanism in the liver, suggesting a new
      link between cell growth and the cell cycle machinery. Furthermore, p21
      suppresses proliferation in the overgrown livers and may play a role in
      preventing cell cycle progression in response to organ size homeostatic
      mechanisms.

PMID- 17517889
TI  - Characterization of anti-heparan sulfate phage display antibodies AO4B08 and
      HS4E4.
AB  - Heparan sulfates (HS) are linear carbohydrate chains, covalently attached to
      proteins, that occur on essentially all cell surfaces and in extracellular
      matrices. HS chains show extensive structural heterogeneity and are functionally
      important during embryogenesis and in homeostasis due to their interactions with
      various proteins. Phage display antibodies have been developed to probe HS
      structures, assess the availability of protein-binding sites, and monitor
      structural changes during development and disease. Here we have characterized two
      such antibodies, AO4B08 and HS4E4, previously noted for partly differential
      tissue staining. AO4B08 recognized both HS and heparin, and was found to interact
      with an ubiquitouys, N-, 2-O-, and 6-O-sulfated saccharide motif, including an
      internal 2-O-sulfate group. HS4E4 turned out to preferentially recognize low
      sulfated HS motifs containing iduronic acid, and N-sulfated as well as N
      acetylated glucosamine residues. Contrary to AO4B08, HS4E4 did not bind highly O
      sulfated structures such as found in heparin.

PMID- 17517890
TI  - A histidine scan to probe the flexibility of the rat P2X2 receptor zinc-binding
      site.
AB  - The response of P2X(2) receptors to submaximal concentrations of ATP is
      potentiated by low levels of extracellular zinc. Histidines 120 and 213 have
      previously been shown to be essential in binding zinc across an intersubunit
      binding site. We tested the flexibility of the zinc-binding site by making
      mutations that had the effect of shifting the two essential histidines up to 13
      residues upstream or downstream from their original positions and then testing
      the ability of the mutated receptors to respond to zinc. Using this method, we
      were able to explore potential orientations of the two regions relative to one
      another. Our data are consistent with a moderately flexible zinc-binding site and
      inconsistent with parallel and anti-parallel orientations of the regions
      surrounding histidines 120 and 213.

PMID- 17517891
TI  - A C-terminal region of signal peptide peptidase defines a functional domain for
      intramembrane aspartic protease catalysis.
AB  - Intramembrane proteolysis is now firmly established as a prominent biological
      process, and structure elucidation is emerging as the new frontier in the
      understanding of these novel membrane-embedded enzymes. Reproducing this unusual
      hydrolysis within otherwise water-excluding transmembrane regions with purified
      proteins is a challenging prerequisite for such structural studies. Here we show
      the bacterial expression, purification, and reconstitution of proteolytically
      active signal peptide peptidase (SPP), a membrane-embedded enzyme in the
      presenilin family of aspartyl proteases. This finding formally proves that,
      unlike presenilin, SPP does not require any additional proteins for proteolysis.
      Surprisingly, the conserved C-terminal half of SPP is sufficient for proteolytic
      activity; purification and reconstitution of this engineered fragment of several
      SPP orthologues revealed that this region defines a functional domain for an
      intramembrane aspartyl protease. The discovery of minimal requirements for
      intramembrane proteolysis should facilitate mechanistic and structural analysis
      and help define general biochemical principles of hydrolysis in a hydrophobic
      environment.

PMID- 17517892
TI  - GRK2 negatively regulates glycogen synthesis in mouse liver FL83B cells.
AB  - G-protein-coupled receptor (GPCR) kinases (GRKs) are serine/threonine kinases
      that desensitize agonist-occupied classical GPCRs. Although the insulin receptor
      (IR) is a tyrosine kinase receptor, the IR also couples to G-proteins and
      utilizes G-protein signaling components. The present study was designed to test
      the hypothesis that GRK2 negatively regulates IR signaling. FL83B cells, derived
      from mouse liver, were treated with insulin and membrane translocation of GRK2
      was determined using immunofluoresecence and Western blotting. Insulin caused an
      increase in the translocation of GRK-2 from cytosol to the plasma membrane. To
      determine the role of GRK2 in IR signaling, GRK2 was selectively down-regulated (
      approximately by 90%) in FL83B cells using a small interfering RNA technique.
      Basal as well as insulin-induced glycogen synthesis (measured by d-[U
      (14)C]glucose incorporation) was increased in GRK2-deficient cells compared with
      control cells. Similarly, GRK2 deficiency increased the basal and insulin
      stimulated phosphorylation of Ser(21) in glycogen synthase kinase-3alpha. Insulin
      induced tyrosine phosphorylation of the IR was similar in control and GRK2
      deficient cells. Basal and insulin-stimulated phosphorylation of Tyr(612) in
      insulin receptor subunit 1 was significantly increased while phosphorylation of
      Ser(307) was decreased in GRK2-deficient FL83B cells compared with control cells.
      Chronic insulin treatment (24 h) in control cells caused an increase in GRK2
      (56%) and a decrease in IR (50%) expression associated with the absence of an
      increase in glycogen synthesis, suggesting impairment of IR function. However,
      chronic insulin treatment (24 h) did not decrease IR expression or impair IR
      effects on glycogen synthesis in GRK2-deficient cells. We conclude that (i) GRK2
      negatively regulates basal and insulin-stimulated glycogen synthesis via a post
      IR signaling mechanism, and (ii) GRK2 may contribute to reduced IR expression and
      function during chronic insulin exposure.

PMID- 17517893
TI  - Rotational catalysis of Escherichia coli ATP synthase F1 sector. Stochastic
      fluctuation and a key domain of the beta subunit.
AB  - A complex of gamma, epsilon, and c subunits rotates in ATP synthase (FoF(1))
      coupled with proton transport. A gold bead connected to the gamma subunit of the
      Escherichia coli F(1) sector exhibited stochastic rotation, confirming a previous
      study (Nakanishi-Matsui, M., Kashiwagi, S., Hosokawa, H., Cipriano, D. J., Dunn,
      S. D., Wada, Y., and Futai, M. (2006) J. Biol. Chem. 281, 4126-4131). A similar
      approach was taken for mutations in the beta subunit key region; consistent with
      its bulk phase ATPase activities, F(1) with the Ser-174 to Phe substitution
      (betaS174F) exhibited a slower single revolution time (time required for 360
      degree revolution) and paused almost 10 times longer than the wild type at one of
      the three 120 degrees positions during the stepped revolution. The pause
      positions were probably not at the "ATP waiting" dwell but at the "ATP
      hydrolysis/product release" dwell, since the ATP concentration used for the assay
      was approximately 30-fold higher than the K(m) value for ATP. A betaGly-149 to
      Ala substitution in the phosphate binding P-loop suppressed the defect of
      betaS174F. The revertant (betaG149A/betaS174F) exhibited similar rotation to the
      wild type, except that it showed long pauses less frequently. Essentially the
      same results were obtained with the Ser-174 to Leu substitution and the
      corresponding revertant betaG149A/betaS174L. These results indicate that the
      domain between beta-sheet 4 (betaSer-174) and P-loop (betaGly-149) is important
      to drive rotation.

PMID- 17517894
TI  - IQGAP1 binds Rap1 and modulates its activity.
AB  - IQGAP1 is a scaffolding protein involved in multiple fundamental cellular
      activities, including transcription, cell-cell attachment, and regulation of the
      cytoskeleton. To function in these pathways, IQGAP1 associates with numerous
      proteins such as actin, calmodulin, E-cadherin, beta-catenin, CLIP-170, and
      components of the mitogen-activated protein kinase pathway. Moreover, IQGAP1
      binds to active Cdc42 and Rac1 but not RhoA or Ras. Here we show that IQGAP1 also
      binds to the small GTPase Rap1. In vitro analysis demonstrates a direct
      interaction between Rap1 and IQGAP1, which is augmented by activation (GTP
      loading) of Rap1. Cdc42 does not modulate the interaction between Rap1 and
      IQGAP1. In contrast, the association is eliminated by calmodulin both in the
      absence and presence of Ca(2+). The binding of Rap1 to a point mutant IQGAP1
      construct that is unable to interact with calmodulin is 2.5-fold more than to
      wild type IQGAP1. Consistent with these findings, Rap1 binds to the IQ region of
      IQGAP1. Confocal microscopy demonstrates that Rap1 and IQGAP1 co-localize at the
      periphery of human epithelial cells but not in the cytoplasm. The interaction has
      functional sequelae. Overexpression of IQGAP1 substantially reduces adhesion
      mediated activation of Rap1. In addition, Rap1 activation by cAMP is attenuated
      in cells that overexpress IQGAP1 and enhanced in cells lacking IQGAP1. These
      findings reveal that the interaction of IQGAP1 with Rap1 differs in several
      respects from its interaction with other small GTPases. Furthermore, our data
      suggest that IQGAP1 may link the calmodulin and Rap1 signaling pathways.

PMID- 17517895
TI  - Structurally unique yeast and mammalian serine-arginine protein kinases catalyze
      evolutionarily conserved phosphorylation reactions.
AB  - The mammalian serine-arginine (SR) protein, ASF/SF2, contains multiple contiguous
      RS dipeptides at the C terminus, and approximately 12 of these serines are
      processively phosphorylated by the SR protein kinase 1 (SRPK1). We have recently
      shown that a docking motif in ASF/SF2 specifically interacts with a groove in
      SRPK1, and this interaction is necessary for processive phosphorylation. We
      previously showed that SRPK1 and its yeast ortholog Sky1p maintain their active
      conformations using diverse structural strategies. Here we tested if the
      mechanism of ASF/SF2 phosphorylation by SRPK is evolutionarily conserved. We show
      that Sky1p forms a stable complex with its heterologous mammalian substrate
      ASF/SF2 and processively phosphorylates the same sites as SRPK1. We further show
      that Sky1p utilizes the same docking groove to bind yeast SR-like protein Gbp2p
      and phosphorylates all three serines present in a contiguous RS dipeptide
      stretch. However, the mechanism of Gbp2p phosphorylation appears to be non
      processive. Thus, there are physical attributes of SR and SR-like substrates that
      dictate the mechanism of phosphorylation, whereas the ability to processively
      phosphorylate substrates is inherent to SR protein kinases.

PMID- 17517896
TI  - Discovery, characterization, and kinetic analysis of an alditol oxidase from
      Streptomyces coelicolor.
AB  - A gene encoding an alditol oxidase was found in the genome of Streptomyces
      coelicolor A3(2). This newly identified oxidase, AldO, was expressed at extremely
      high levels in Escherichia coli when fused to maltose-binding protein. AldO is a
      soluble monomeric flavoprotein with subunits of 45.1 kDa, each containing a
      covalently bound FAD cofactor. From sequence alignments with other flavoprotein
      oxidases, it was found that AldO contains a conserved histidine (His(46)) that is
      typically involved in covalent FAD attachment. Covalent FAD binding is not
      observed in the H46A AldO mutant, confirming its role in covalent attachment of
      the flavin cofactor. Steady-state kinetic analyses revealed that wild-type AldO
      is active with several polyols. The alditols xylitol (K(m) = 0.32 mm, k(cat) = 13
      s(-1)) and sorbitol (K(m) = 1.4 mm, k(cat) = 17 s(-1)) are the preferred
      substrates. From pre-steady-state kinetic analyses, using xylitol as substrate,
      it can be concluded that AldO mainly follows a ternary complex kinetic mechanism.
      Reduction of the flavin cofactor by xylitol occurs at a relatively high rate (99
      s(-1)), after which a second kinetic event is observed, which is proposed to
      represent ring closure of the formed aldehyde product, yielding the hemiacetal of
      d-xylose. Reduced AldO readily reacts with molecular oxygen (1.7 x 10(5) m(-1) s(
      1)), which confirms that the enzyme represents a true flavoprotein oxidase.

PMID- 17517897
TI  - Specific protein domains mediate cooperative assembly of HuR oligomers on AU-rich
      mRNA-destabilizing sequences.
AB  - The RNA-binding factor HuR is a ubiquitously expressed member of the Hu protein
      family that binds and stabilizes mRNAs containing AU-rich elements (AREs). Hu
      proteins share a common domain organization of two tandemly arrayed RNA
      recognition motifs (RRMs) near the N terminus, followed by a basic hinge domain
      and a third RRM near the C terminus. In this study, we engineered recombinant
      wild-type and mutant HuR proteins lacking affinity tags to characterize their ARE
      binding properties. Using combinations of electrophoretic mobility shift and
      fluorescence anisotropy-based binding assays, we show that HuR can bind ARE
      substrates as small as 13 nucleotides with low nanomolar affinity, but forms
      cooperative oligomeric protein complexes on ARE substrates of at least 18
      nucleotides in length. Analyses of deletion mutant proteins indicated that RRM3
      does not contribute to high affinity recognition of ARE substrates, but is
      required for cooperative assembly of HuR oligomers on RNA. Finally, the hinge
      domain between RRM2 and RRM3 contributes significant binding energy to HuR.ARE
      complex formation in an ARE length-dependent manner. The hinge does not enhance
      RNA-binding activity by increased ion pair formation despite extensive positive
      charge within this region, and it does not thermodynamically stabilize protein
      folding. Together, the results define distinct roles for the HuR hinge and RRM3
      domains in formation of cooperative HuR.ARE complexes in solution.

PMID- 17517898
TI  - A robust, target-driven, cell-based assay for checkpoint kinase 1 inhibitors.
AB  - Checkpoint kinase 1 (Chk1), a serine/threonine kinase, plays an important role in
      DNA damage checkpoint control and is an attractive target for cancer treatment.
      To develop a Chk1-specific cell-based assay, stable clones were established in
      which Chk1 kinase domain fused at its N-terminus with p53 through 4 tandem
      repeats of Gly-Gly-Gly-Gly-Ser was expressed in an inducible manner. Chk1 kinase
      specificity of the phosphorylation of fused p53 was confirmed by the experiments
      with a kinase-inactive Chk1. Only in the presence of an inducer molecule was
      phosphorylation of p53 at Ser-15 in the stable clones induced. Furthermore, its
      assay performance proved acceptable for high-throughput screening applications,
      judging from the Z' factor values (> 0.77). Finally, the cell-based assay thus
      established yielded structure-activity relationship data for a small set of test
      inhibitors of Chk1 within cells. Collectively, these results demonstrate that the
      established cell-based assay provides a novel and highly sensitive cellular
      platform for Chk1 inhibitor discovery.

PMID- 17517899
TI  - Quality control procedures for dose-response curve generation using nanoliter
      dispense technologies.
AB  - With the advancement of high-throughput biomolecular screening techniques to the
      lead optimization stage, there is a critical need to quality control (QC) dose
      response curves generated by robotic liquid handlers to ensure accurate affinity
      determinations. One challenge in evaluating the performance of liquid handlers is
      identifying and validating a robust method for testing dispense volumes across
      different instruments. Although traditional automated liquid handlers are still
      considered the standard platform in many laboratories, nanoliter dispensers are
      becoming more common and pose new challenges for routine quality control
      procedures. For example, standard gravimetric measurements are unreliable for
      testing the accuracy of nanoliter liquid dispenses. However, nanoliter dispensing
      technology allows for the conservation of compound, reduces compound carryover
      from well to well through discrete dispenses, and eliminates the need for
      intermediate compound dilution steps to achieve a low final DMSO assay
      concentration. Moreover, an intermediate dilution step in aqueous solution might
      result in compound precipitation at high concentrations. This study compared
      representative automation procedures done on a variety of liquid dispensers,
      including manual, traditional, and nanodispense volumes. The data confirmed the
      importance of establishing robust QC procedures for dose-response generation in
      addition to accuracy and precision determinations for each instrument, and they
      validated the use of nanoliter pipettors for dose-response testing. The results
      of this study also support the requirement for thorough mixing during serial
      compound dilutions prepared for high-throughput lead optimization strategies
      using traditional liquid handlers.

PMID- 17517900
TI  - Development of a Ca(2+)-activated photoprotein, Photina, and its application to
      high-throughput screening.
AB  - The present work describes the engineering and characterization of a new Ca(2+)
      activated photoprotein (Photina) and its use in mammalian cell lines for
      implementation of flash luminescence cell-based assays for high-throughput
      screening (HTS). When used to measure the activation of 2 G protein-coupled
      receptors (GPCRs), targeting Photina to the mitochondria increased the signal
      strength as compared to the normal cytoplasmic expression of Photina. The
      mitochondrial-targeted Photina also produced a higher signal-to-noise ratio than
      conventional calcium dyes and a consistently stronger signal than aequorin when
      tested under equivalent conditions. MitoPhotina provided strong and reliable
      results when used to measure the activity of purinergic receptors endogenously
      expressed in the Chinese Hamster Ovary cells and heterologously expressed GPCRs
      in response to their cognate ligands. Several different types of flash
      luminescence plate readers (FLIPR(3), FLIPR(TETRA), CyBi-Lumax flash HT, Lumilux,
      Lumibox) in different plate formats (96, 384, 1536 wells) were used to validate
      the use of Photina in HTS. The cell number had to be adjusted to correspond to
      the qualities of the different readers, but once so adjusted, it provided
      equivalent results on each device. The results obtained show robust and
      reproducible light signals that offer new possibilities for application of
      photoproteins to the generation of cell-based assays for HTS.

PMID- 17517901
TI  - A selective cellular screening assay for B-Raf and c-Raf kinases.
AB  - The Ras/Raf signaling pathway has been recognized as an important process in
      cancer biology. Recently, activating mutations in the BRAF gene were reported to
      be present in approximately 66% of malignant melanomas as well as other
      malignancies such as colon cancer. Here, the authors report the development of a
      B-Raf-specific cellular assay to profile cell-active B-Raf inhibitors. Expression
      of the active B-Raf mutant (V600E) and the kinase-inactive form of its substrate,
      MEK1, was regulated by mifepristone, and the catalytic activity of B-Raf was
      monitored by following MEK1 phosphorylation. Target specificity was ensured
      because the phosphorylation of MEK1 was significantly inhibited when kinase
      inactive B-Raf was used in place of the active kinase. A cellular c-Raf assay was
      similarly established to monitor the selectivity between B-Raf and c-Raf. Z'
      factor values were consistently above 0.50 with either kinase, indicating that
      assay performance was sufficiently robust for use as cellular profiling assays.
      The authors used this system to demonstrate that the selectivity profile of
      compounds targeted against B-Raf and c-Raf kinases could be quantitatively
      determined. This platform provides a quantitative cellular readout for a spectrum
      of specific inhibitors of B-Raf and c-Raf kinases that is particularly suitable
      for use in drug discovery.

PMID- 17517902
TI  - An improved beta-lactamase reporter assay: multiplexing with a cytotoxicity
      readout for enhanced accuracy of hit identification.
AB  - A problem inherent to the use of cellular assays for drug discovery is their
      sensitivity to cytotoxic compounds, which can result in false hits from certain
      compound screens. To alleviate the need to follow-up hits from a reporter assay
      with a separate cytotoxicity assay, the authors have developed a multiplexed
      assay that combines the readout of a beta-lactamase reporter with that of a
      homogeneous cytotoxicity indicator. Important aspects to the development of the
      multiplexed format are addressed, including results that demonstrate that the
      IC(50) values of 40 select compounds in a beta-lactamase reporter assay for
      nuclear factor kappa B and SIE pathway antagonists are not affected by the
      addition of the cytotoxicity indicator. To demonstrate the improvement in hit
      confirmation, the multiplexed assay was used to perform a small-library screen
      (7728 compounds) for serotonin 5HT1A receptor antagonists. Hits identified from
      analysis of the beta-lactamase reporter data alone were compared to those hits
      determined when the reporter and cytotoxicity data generated from the multiplexed
      assay were combined. Confirmation rates were determined from compound follow-up
      using dose-response analysis of the potential antagonist hits identified by the
      initial screen. In this representative screen, the multiplexed assay approach
      yielded a 19% reduction in the number of compounds flagged for follow-up, with a
      37% decrease in the number of false hits, demonstrating that multiplexing a beta
      lactamase reporter assay with a cytotoxicity readout is a highly effective
      strategy for reducing false hit rates in cell-based compound screening assays.

PMID- 17517903
TI  - High-content imaging analysis of the knockdown effects of validated siRNAs and
      antisense oligonucleotides.
AB  - High-content imaging (HCI) provides researchers with a powerful tool for
      understanding cellular processes. Although phenotypic analysis generated through
      HCI is a potent technique to determine the overall cellular effects of a given
      treatment, it frequently produces complex data sets requiring extensive
      interpretation. The authors developed statistical analyses to decrease the time
      spent to determine the outcome of each HCI assay and to better understand complex
      phenotypic changes. To test these tools, the authors performed a comparison
      experiment between 2 types of oligonucleotide-mediated gene silencing (OMGS),
      antisense oligonucleotides (ASOs), and short, double-stranded RNAs (siRNAs).
      Although similar in chemical structure, these 2 methods differ in cellular
      mechanism of action and off-target effects. Using a library of 50 validated ASOs
      and siRNAs to the same targets, the authors characterized the differential
      effects of these 2 technologies using a HeLa cell G2-M cell cycle assay. Although
      knockdown of a variety of targets by ASOs or siRNAs affected the cell cycle
      profile, few of those targets were affected by both ASOs and siRNAs. Distribution
      analysis of population changes induced through target knockdown led to the
      identification of targets that, when inhibited, could affect the G2-M transition
      in the cell cycle in a statistically significant manner. The distinctly different
      mechanisms of action of these 2 forms of gene silencing may help define the use
      of these treatments in both clinical and research environments.

PMID- 17517904
TI  - A new method with flexible and balanced control of false negatives and false
      positives for hit selection in RNA interference high-throughput screening assays.
AB  - The z-score method and its variants for testing mean difference are commonly used
      for hit selection in high-throughput screening (HTS) assays. Strictly
      standardized mean difference (SSMD) offers a way to measure and classify the
      short interfering RNA (siRNA) effects. In this article, based on SSMD, the
      authors propose a new testing method for hit selection in RNA interference (RNAi)
      HTS assays. This SSMD-based method allows the differentiation between siRNAs with
      large and small effects on the assay output and maintains flexible and balanced
      control of both the false-negative rate, in which the siRNAs with strong effects
      are not selected as hits, and the restricted false-positive rate, in which the
      siRNAs with weak or no effects are selected as hits. This method directly
      addresses the size of siRNA effects represented by the strength of difference
      between an siRNA and a negative reference, whereas the classic z-score method and
      t-test of testing no mean difference address whether the mean of an siRNA is
      exactly the same as the mean of a negative reference. This method can readily
      control the false-negative rate, whereas it is nontrivial for the classic z-score
      method and t-test to control the false-negative rate. Therefore, theoretically,
      the SSMD-based method offers better control of the sizes of siRNA effects and the
      associated false-positive and false-negative rates than the commonly used z-score
      method and t-test for hit selection in HTS assays. The SSMD-based method should
      generally be applicable to any assay in which the end point is a difference in
      signal compared to a reference sample, including those for RNAi, receptor,
      enzyme, and cellular function.

PMID- 17517905
TI  - pH-Insensitive FRET voltage dyes.
AB  - Many high-throughput ion channel assays require the use of voltage-sensitive dyes
      to detect channel activity in the presence of test compounds. Dye systems
      employing Forster resonance energy transfer (FRET) between 2 membrane-bound dyes
      are advantageous in combining high sensitivity, relatively fast response, and
      ratiometric output. The most widely used FRET voltage dye system employs a
      coumarin fluorescence donor whose excitation spectrum is pH dependent. The
      authors have validated a new class of voltage-sensitive FRET donors based on a
      pyrene moiety. These dyes are significantly brighter than CC2-DMPE and are not pH
      sensitive in the physiological range. With the new dye system, the authors
      demonstrate a new high-throughput assay for the acid-sensing ion channel (ASIC)
      family. They also introduce a novel method for absolute calibration of voltage
      sensitive dyes, simultaneously determining the resting membrane potential of a
      cell.

PMID- 17517906
TI  - Optimized and automated protocols for high-throughput screening of amylosucrase
      libraries.
AB  - This article describes the design and validation of a general procedure for the
      high-throughput isolation of amylosucrase variants displaying higher
      thermostability or increased resistance to organic solvents. This procedure
      consists of 2 successive steps: an in vivo selection that eliminates inactive
      variants followed by automated screening of active variants to isolate mutants
      displaying enhanced features. The authors chose an Escherichia coli expression
      vector, allowing a high production rate of the recombinant enzyme in miniaturized
      culture conditions. The screening assay was validated by minimizing variability
      for various parameters of the protocol, especially bacterial growth and protein
      production in cultures in 96-well microplates. Recombinant amylosucrase
      production was normalized by decreasing the coefficient of variance from 27% to
      12.5%. Selective screening conditions were defined to select variants displaying
      higher thermostability or increased resistance to organic solvents. A first
      generation amylosucrase variant library, constructed by random mutagenesis, was
      subjected to this procedure, yielding a mutant displaying a 25-fold increased
      stability at 50 degrees C compared to the parental wild-type enzyme.

PMID- 17517907
TI  - The health status of retired American football players: Super Bowl III revisited.
AB  - BACKGROUND: Despite a perception that retired professional football players have
      poor health, there are little supporting data. HYPOTHESIS: Retired football
      players have poor health compared with age-matched population norms. STUDY
      DESIGN: Cross-sectional study; Level of evidence, 4. METHODS: Thirty-six of 41
      members of the 1969 Super Bowl winning team were contacted 35 years after that
      event (3 were deceased, and no contact information was available for 2). Players
      completed an SF-36 health survey and a medical history and football-specific
      questionnaire. Each player's football-related injury history before 1969 was
      documented from medical records. It was estimated that there was 80% power to
      detect a 10% difference in physical and mental health scores between the retired
      football players (age, 62 +/- 3 y) and population norms (n = 741) at an alpha
      level of 0.05. RESULTS: SF-36 scores for physical and mental health were not
      different from age-matched norms (physical health P = .69; mental health P =
      .49). The most prevalent medical conditions were arthritis (24 of 36 players),
      hypertension (13 of 36 players), and chronic low back pain (13 of 36 players). SF
      36 physical health scores were 21% lower in players with arthritis (P < .01) and
      back pain (P < .05) compared with the other players. Physical health scores were
      19% above normal for players without arthritis (P < .01) and not different from
      normal for players with arthritis (6% lower; P = .6). Four of 8 players who had
      major ligamentous injuries to the knee before 1969 had total knee arthroplasty in
      the intervening years, compared with 3 of the remaining 28 players (P < .05). The
      men played professional football for 8.3 +/- 3.8 years, and 33 players (94%)
      reported having had "very fulfilling" (n = 24) or "somewhat fulfilling" (n = 9)
      careers. CONCLUSION: These professional football players had long and fulfilling
      careers with no apparent long-term detrimental effects on physical or mental
      health scores despite a high prevalence of arthritis.

PMID- 17517908
TI  - Nonirradiated versus irradiated Achilles allograft: in vivo failure comparison.
AB  - BACKGROUND: Many studies suggest that gamma irradiation decreases allograft
      strength in a dose-dependent manner. No study has demonstrated that this decrease
      in strength translates into higher clinical failures. HYPOTHESIS: Irradiation of
      allograft tissue will lead to higher early clinical failure in anterior cruciate
      ligament (ACL) reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3.
      METHODS: Medical records were reviewed for 90 consecutive patients who had
      received Achilles allograft reconstruction for unilateral primary ACL injuries at
      one institution between July 2001 and June 2002. One half of patients received
      nonirradiated Achilles allograft and the other half received irradiated Achilles
      allograft at a dose range of 2.0 to 2.5 Mrad. The ACL allograft reconstructions
      were performed using the same surgical technique. The rehabilitation program was
      identical for both groups. All clinical failures were recorded. RESULTS: At least
      6 months' follow-up was available on 42 subjects in the nonirradiated group and
      33 subjects in the irradiated group. A significant difference was noted in early
      failure rates between the groups (P <.01). The nonirradiated group had 1 in 42
      (2.4%) catastrophic failure. In the irradiated group, 11 of 33 (33%) Achilles
      tendon grafts failed. CONCLUSIONS: Less than satisfactory results led the senior
      authors to discontinue the use of irradiated allografts in ACL surgery. Continued
      research into alternatives to gamma irradiation is needed.

PMID- 17517910
TI  - Beyond intuitive modeling: combining biophysical models with innovative
      experiments to move the circadian clock field forward.
AB  - Two major approaches have been used to model circadian clocks. Qualitative
      modeling, used prior to the recent wealth of detailed molecular knowledge, makes
      general predictions but cannot provide detailed mechanistic insights. The more
      recent biophysical approach, on the other hand, incorporates the biochemical
      events that drive the clock and can make detailed and testable molecular
      predictions. These predictions are being tested using new experimental techniques
      that measure reaction kinetics and the behavior of individual cells. A joint
      modeling and experimental approach has recently been used to understand how
      mutations affecting phosphorylation can lead to a short circadian period in tau
      mutant hamsters and in humans with familial advanced sleep phase syndrome
      (FASPS). Another recent study has revealed novel single-cell phenotypes of clock
      gene mutations, demanding revision of current biophysical models yet validating
      certain model predictions that were previously overlooked. A new paradigm for
      clock research is emerging in which modeling inspires new experimental efforts,
      experimental data inspire new modeling efforts, and joint modeling/experimental
      studies lead to a deeper understanding of mammalian circadian rhythms.

PMID- 17517911
TI  - Modeling the behavior of coupled cellular circadian oscillators in the
      suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) in the hypothalamus is the site of the master
      circadian clock in mammals, a complex tissue composed of multiple, coupled,
      single-cell circadian oscillators. Mathematical modeling is now providing
      insights on how individual SCN cells might interact and assemble to create an
      integrated pacemaker that governs the circadian behavior of whole animals. In
      this article, we will discuss the neurobiological constraints for modeling SCN
      behavior, system precision, implications of cellular heterogeneity, and analysis
      of heterogeneously coupled oscillator networks. Mathematical approaches will be
      critical for better understanding intercellular interactions within the SCN.

PMID- 17517912
TI  - Neuronal models for sleep-wake regulation and synaptic reorganization in the
      sleeping hippocampus.
AB  - In this article, we discuss mathematical models that address the control of sleep
      wake behavior in the infant and adult rodent and a model that addresses changes
      in single-cell firing patterns in the hippocampus across wake and rapid eye
      movement (REM) sleep states. Each of the models describes the dynamics of
      experimentally identified neuronal components--either the firing activity of wake
      and sleep-promoting neuronal populations or the spiking activity of hippocampal
      pyramidal neurons. Our discussion of each model illustrates how a mathematical
      model that describes the temporal dynamics of the modeled neuronal components can
      reveal specifics about proposed neuronal mechanisms that underlie sleep-wake
      regulation or sleep-specific firing patterns. For example, the dynamics of the
      models developed for sleep-wake regulation in the infant rodent lend insight into
      the involved brain-stem neuronal populations and the evolution of the network
      during maturation. The results of the model for sleep-wake regulation in the
      adult rodent suggest distinct properties of the involved neuronal populations and
      their interactions that account for long-lasting and brief waking bouts. The
      dynamics of the model for sleep-specific hippocampal neural activity proposes
      neural mechanisms to account for observed activity changes that can invoke
      synaptic reorganization associated with learning and memory consolidation.

PMID- 17517913
TI  - Uncovering physiologic mechanisms of circadian rhythms and sleep/wake regulation
      through mathematical modeling.
AB  - Mathematical models of neurobehavioral function are useful both for understanding
      the underlying physiology and for predicting the effects of rest-activity-work
      schedules and interventions on neurobehavioral function. In a symposium titled
      "Modeling Human Neurobehavioral Performance I: Uncovering Physiologic Mechanisms"
      at the 2006 Society for Industrial and Applied Mathematics/Society for
      Mathematical Biology (SIAM/SMB) Conference on the Life Sciences, different
      approaches to modeling the physiology of human circadian rhythms, sleep, and
      neurobehavioral performance and their usefulness in understanding the underlying
      physiology were examined. The topics included key elements of the physiology that
      should be included in mathematical models, a computational model developed within
      a cognitive architecture that has begun to include the effects of extended wake
      on information-processing mechanisms that influence neurobehavioral function, how
      to deal with interindividual differences in the prediction of neurobehavioral
      function, the applications of systems biology and control theory to the study of
      circadian rhythms, and comparisons of these methods in approaching the
      overarching questions of the underlying physiology and mathematical models of
      circadian rhythms and neurobehavioral function. A unifying theme was that it is
      important to have strong collaborative ties between experimental investigators
      and mathematical modelers, both for the design and conduct of experiments and for
      continued development of the models.

PMID- 17517914
TI  - Developing mathematical models of neurobehavioral performance for the "real
      world".
AB  - Work-related operations requiring extended wake durations, night, or rotating
      shifts negatively affect worker neurobehavioral performance and health. These
      types of work schedules are required in many industries, including the military,
      transportation, and health care. These industries are increasingly using or
      considering the use of mathematical models of neurobehavioral performance as a
      means to predict the neurobehavioral deficits due to these operational demands,
      to develop interventions that decrease these deficits, and to provide additional
      information to augment existing decision-making processes. Recent advances in
      mathematical modeling have allowed its application to real-world problems.
      Developing application-specific expertise is necessary to successfully apply
      mathematical models, in part because development of new algorithms and methods
      linking the models to the applications may be required. During a symposium,
      "Modeling Human Neurobehavioral Performance II: Towards Operational Readiness,"
      at the 2006 SIAM-SMB Conference on the Life Sciences, examples of the process of
      applying mathematical models, including model construction, model validation, or
      developing model-based interventions, were presented. The specific applications
      considered included refining a mathematical model of sleep/wake patterns of
      airline flight crew, validating a mathematical model using railroad operations
      data, and adapting a mathematical model to develop appropriate countermeasure
      recommendations based on known constraints. As mathematical models and their
      associated analytical methods continue to transition into operational settings,
      such additional development will be required. However, major progress has been
      made in using mathematical model outputs to inform those individuals making
      schedule decisions for their workers.

PMID- 17517915
TI  - Dynamics of the adjustment of clock gene expression in the rat suprachiasmatic
      nucleus to an asymmetrical change from a long to a short photoperiod.
AB  - The molecular clockwork of the rat suprachiasmatic nucleus, the site of the
      circadian clock, is affected by the photoperiod (Sumova et al., 2003). The aim of
      the present study was to partly elucidate the dynamics of the adjustment of the
      clockwork to a change from a long to a short photoperiod accomplished by an
      asymmetrical prolongation of the dark period into the morning hours. Rats
      maintained under a regime with 16 h of light and 8 h of darkness per day (LD
      16:8) were transferred to LD 8:16, and after 2, 3, and 13 days, daily profiles of
      Per1, Per2, Bmal1, and Cry1 mRNA were assessed by in situ hybridization. The
      rhythms of Per1, Per2, and Bmal1 expression adjusted to the change from a long to
      a short photoperiod with larger phase delays of the morning Per mRNA rise and
      Bmal1 mRNA decline than of the evening and nighttime Per mRNA decline and Bmal1
      mRNA rise. The rhythm of Cry1 expression adjusted to the change by parallel
      delays of the Cry1 mRNA rise and decline. Adjustment of the Cry1 mRNA rhythm to
      short days was almost accomplished within 13 days, whereas adjustment of the Per1
      and Bmal1 mRNA rhythms took longer. Different dynamics of the adjustment of
      rhythms in clock gene expression to a change from a long to a short photoperiod
      suggests complex resetting effects of the photoperiod change.

PMID- 17517916
TI  - Association between morningness-eveningness and behavioral/emotional problems
      among adolescents.
AB  - Adolescent eveningness is associated with age, parental monitoring, daytime
      sleepiness, sleep problems, moodiness, and the use of coffee. This study
      investigated the association between adolescent morningness-eveningness and
      psychopathology, substance use, and suicidality in 1332 students ages 12 to 13.
      Each student-participant completed the Chinese version of the Child
      Morningness/Eveningness Scale (CMES), the Pubertal Development Scale, and a
      questionnaire about their sleep schedule, trouble sleeping, habitual substance
      use, and suicidality. Their mothers completed the Child Behavioral Checklist and
      Chinese Health Questionnaire. The morning (n = 412), intermediate (n = 740), and
      evening (n = 180) groups were operationally defined by the CMES t scores. The
      mixed model was used for data analysis. The evening group had shorter weekday
      sleep time, longer weekend sleep time, more daytime napping, and greater sleep
      compensation on weekends and was more likely than the other 2 groups to have
      behavioral/emotional problems, suicidality, and habitual substance use.
      Internalizing and externalizing problems partially explained the association
      between eveningness, substance use, and suicidality. The findings suggest that
      eveningness may be an indicator for adolescents with behavioral/emotional
      problems and risky behaviors and suggest an investigation for possible
      intervention.

PMID- 17517917
TI  - The Presence of UG-repeat sequences in the 3'-UTRs of reporter luciferase mRNAs
      mediates circadian expression and can determine acrophase in Chlamydomonas
      reinhardtii.

PMID- 17517918
TI  - Which aspects of morningness-eveningness change with age?

PMID- 17517919
TI  - A structural basis for interferon-alpha-receptor interactions.
AB  - Interferon (IFN)-alpha subtypes exhibit differences in biological potencies based
      on their affinity interactions with the IFN receptor subunits, IFNAR1 and IFNAR2.
      Using available three-dimensional structural information and computational
      biology, homology models of human IFN-alpha1, human IFN-alpha8, IFN alfacon-1,
      and murine IFN-alpha4 were derived and docked with the extracellular region of
      human IFNAR2 to evaluate the behavior of potential interacting residue pairs and
      characterize the nature of the IFN-IFNAR2 binding interfaces. The data suggest
      that IFN afacon-1 has 9 optimal interactions with IFNAR2, comprising hydrophobic,
      electrostatic, and hydrogen bonding. Human IFN-alpha2 exhibits 8 optimal
      interactions, human IFN-alpha1, 7, and murine IFN-alpha4 exhibits the least
      number of optimal interactions, at 5. A model of IFNAR1 was generated, taking
      into consideration the IFNAR1 extracellular domain interaction with cell surface
      glycosphingolipids, putative ligand interaction residues, and residues
      stabilizing the structural integrity of IFNAR. IFNAR1 was then docked with the
      various IFN-IFNAR2 complexes to describe the complete extracellular receptor
      pocket with bound IFN. These data provide insights into the species specificity
      of IFN-alphas: residues in murine IFN-alpha4 that preclude strong affinity
      interactions with human IFNAR because of steric crowding and residues in human
      IFN-alpha8 that resemble a receptor interactive domain in murine IFN-alpha4, are
      described.

PMID- 17517920
TI  - Conditional glucocorticoid receptor expression in the heart induces atrio
      ventricular block.
AB  - Corticosteroid hormones (aldosterone and glucocorticoids) and their receptors are
      now recognized as major modulators of cardiovascular pathophysiology, but their
      specific roles remain elusive. Glucocorticoid hormones (GCs), which are widely
      used to treat acute and chronic diseases, often have adverse cardiovascular
      effects such as heart failure, hypertension, atherosclerosis, or metabolic
      alterations. The direct effects of GC on the heart are difficult to evaluate, as
      changes in plasma GC concentrations have multiple consequences due to the
      ubiquitous expression of the glucocorticoid receptor (GR), resulting in secondary
      effects on cardiac function. We evaluated the effects of GR on the heart in a
      conditional mouse model in which the GR was overexpressed solely in
      cardiomyocytes. The transgenic mice displayed electrocardiogram (ECG)
      abnormalities: a long PQ interval, increased QRS and QTc duration as well as
      chronic atrio-ventricular block, without cardiac hypertrophy or fibrosis. The ECG
      alterations were reversible on GR expression shutoff. Isolated ventricular
      cardiomyocytes showed major ion channel remodeling, with decreases in I(Na),
      I(to), and I(Kslow) activity and changes in cell calcium homeostasis (increase in
      C(al), in Ca2+ transients and in sarcoplasmic reticulum Ca2+ load). This
      phenotype differs from that observed in mice overexpressing the mineralocorticoid
      receptor in the heart, which displayed ventricular arrhythmia. Our mouse model
      highlights novel effects of GR activation in the heart indicating that GR has
      direct and specific cardiac effects in the mouse.

PMID- 17517921
TI  - Science to Practice: Is there a role for MR imaging in monitoring gene therapy
      response?

PMID- 17517922
TI  - Teleradiology. Part I. History and clinical applications.

PMID- 17517923
TI  - What we do not yet know in the radiologic sciences.

PMID- 17517924
TI  - Pandemic influenza.

PMID- 17517925
TI  - Evidence-based practice in radiology education: why and how should we teach it?
AB  - Evidence-based practice in radiology (EBR) is becoming firmly established as a
      method to enhance the knowledge and fill the need for further knowledge within
      the profession. It has been identified as an essential part of the training
      program, both at medical school and at the resident and/or fellowship level. This
      review aims to describe the essential components of EBR, to describe the
      educational theories that may be applied to developing EBR within the curriculum,
      and to give several models that have been shown to result in greater student and
      resident participation in the search and exploration of evidence-based practice.

PMID- 17517926
TI  - Imaging techniques for detection and management of endoleaks after endovascular
      aortic aneurysm repair.
AB  - Endovascular aortic aneurysm repair (EVAR) is evolving into a viable alternative
      to open surgical repair for many patients with abdominal and thoracic aortic
      aneurysms. Endoleak development is a complication of EVAR and represents one of
      the limitations of this procedure. Endoleaks represent blood flow outside the
      stent-graft lumen but within the aneurysm sac. Lifelong imaging surveillance of
      patients after EVAR is critical to detect endoleaks for the patient's benefit and
      to determine the long-term performance of the stent-graft. Although computed
      tomographic angiography is the most commonly used examination for imaging
      surveillance, magnetic resonance angiography, ultrasonography, and digital
      subtraction angiography all have a role in endoleak detection and management.
      This review will focus on imaging techniques used for endoleak detection and the
      role imaging surveillance plays in the overall care of the post-EVAR patient.

PMID- 17517927
TI  - Evidence-based target recall rates for screening mammography.
AB  - PURPOSE: To retrospectively identify target recall rates for screening
      mammography on the basis of how sensitivity shifts with recall rate. MATERIALS
      AND METHODS: The study group included 1 872 687 subsequent and 171 104 first
      screening mammograms from 1996 to 2001 from 172 and 139 facilities, respectively,
      in six sites of the Breast Cancer Surveillance Consortium. Institutional review
      board (IRB) approval was obtained from each site. Informed consent requirements
      of the IRBs were followed. The study was HIPAA compliant. Recall rate was defined
      as the percentage of screening studies for which further work-up was recommended
      by the radiologist. Sensitivity was defined as the proportion of cancers that
      were detected at screening mammography. Piecewise linear regression was used to
      model sensitivity as a function of recall rate. This model allows detection of
      critical recall rates in which significant changes (shifts) occurred in the rates
      that sensitivity increased with increasing recall rate. Rates were interpreted as
      number of additional work-ups per additional cancer detected (AW/ACD) or, in
      other words, the estimated number of additional women needed to be recalled at a
      given rate to detect one additional cancer. RESULTS: For first mammograms, a
      single shift in the estimated AW/ACD rate occurred at a recall rate of 10.0%,
      with the rate jumping dramatically from 35 to 172. For subsequent mammograms,
      four shifts were identified. At a recall rate of 6.7%, the estimated AW/ACD
      increased from 80 to 132, which rendered it the highest desirable target recall
      rate. At a recall rate of 12.3%, the estimated AW/ACD was 304, which suggests
      little benefit for any higher recall rate. CONCLUSION: Recall rates of 10.0% for
      first and 6.7% for subsequent mammograms are recommended targets on the basis of
      their AW/ACD rates (less than 100).

PMID- 17517928
TI  - Detection of pulmonary vein and left atrial scar after catheter ablation with
      three-dimensional navigator-gated delayed enhancement MR imaging: initial
      experience.
AB  - PURPOSE: To prospectively evaluate whether scar caused by radiofrequency (RF)
      ablation of the left atrium (LA) in patients with atrial fibrillation can be
      depicted with high-spatial-resolution delayed enhancement magnetic resonance (MR)
      imaging. MATERIALS AND METHODS: All 23 subjects (16 men, seven women; mean age,
      54 years +/- 13 [standard deviation]) provided written informed consent; the
      study was approved by the local institutional review board and was HIPAA
      compliant. A high-spatial-resolution free-breathing delayed enhancement MR
      imaging method was developed to detect scar (ie, ablated tissue) in the LA and
      pulmonary veins (PVs). The LA in 15 patients before ablation and in 18 patients
      at least 30 days after ablation was examined. A reader with 4 years of experience
      assessed presence of delayed enhancement on images and circumferential
      completeness. Signal-to-noise and contrast-to-noise ratios were measured and
      compared with an unpaired t test. The relationship between measurements of
      enhancement thickness at the interatrial septum and the number of days after
      ablation was investigated. RESULTS: No subject demonstrated preablation delayed
      enhancement of the atrial or PV wall, whereas postablation delayed enhancement
      was identified in all (100%). In patients after ablation, a partial to completely
      circumferential delayed enhancement pattern could be identified for the left
      inferior PV that encompassed 88% +/- 11 of the circumference, but only 62% of
      patients demonstrated more than 90% circumferential delayed enhancement. The
      signal-to-noise ratio of blood was 12, and the signal-to-noise ratios of the pre-
      and postablation left atrial wall were 15 and 22, respectively (P<.05). A
      relationship between delayed enhancement wall thickness and the inverse of the
      time interval from ablation was identified (P<.05). CONCLUSION: High-spatial
      resolution delayed enhancement MR imaging allows noninvasive identification of
      scar induced by RF ablation following isolation therapy of the PV.

PMID- 17517929
TI  - Diagnostic accuracy of image postprocessing methods for the detection of coronary
      artery stenoses by using multidetector CT.
AB  - PURPOSE: To retrospectively evaluate the diagnostic accuracy of multidetector
      computed tomography (CT) coronary angiography for detection of hemodynamically
      significant (>or=50%) stenoses by using various image postprocessing methods,
      with conventional coronary angiography as the reference standard. MATERIALS AND
      METHODS: The analysis used data from previous studies, use of which had been
      approved by the Institutional Review Board. Sixteen-section multidetector CT data
      sets for 40 patients (30 men, 10 women; mean age 56 years +/- 8; mean heart rate,
      61 beats per minute +/- 6) were evaluated. Six independent investigators
      evaluated the data sets for the presence of stenoses with diameter reduction of
      50% or more, by using either exclusively transverse images, free oblique
      multiplanar reconstructions (MPRs), free oblique maximum intensity projections
      (MIPs, 5 mm thick), prerendered curved MPRs, prerendered curved MIPs, or
      prerendered three-dimensional volume rendered reconstructions (VRTs). Evaluation
      results were compared with conventional coronary angiography for each artery in a
      blinded fashion (chi(2) test). RESULTS: Overall, 35 coronary artery stenoses were
      present. Percentage of evaluable arteries and accuracy for detecting stenosis
      (percentages of accurately classified arteries were, respectively, 99% and 88%
      for transverse, 99% and 91% for oblique MPR, 94% and 86% for oblique MIP, 94% and
      83% for curved MIP, 93% and 81% for curved MPR, and 91% and 73% for VRT).
      Accuracy was significantly higher for oblique MPR than for curved MPR (P=.01),
      curved MIP (P=.03), and VRT (P<.001). CONCLUSION: The evaluation of multidetector
      CT coronary angiography with interactive image display methods, especially
      interactive oblique MPRs, permits higher diagnostic accuracy than evaluation of
      prerendered images (curved MPR, curved MIP, or VRT images).

PMID- 17517930
TI  - CT perfusion for determination of pharmacologically mediated blood flow changes
      in an animal tumor model.
AB  - PURPOSE: To prospectively compare single- and multisection computed tomographic
      (CT) perfusion for tumor blood flow determination in an animal model. MATERIALS
      AND METHODS: All animal protocols and experiments were approved by the
      institutional animal care and use committee before the study was initiated. R3230
      mammary adenocarcinoma was implanted in 11 rats. Tumors (18-20 mm) were scanned
      with dynamic 16-section CT at baseline and after administration of arsenic
      trioxide, which is known to cause acute reduction in blood flow. The
      concentration of arsenic was titrated (0-6 mg of arsenic per kilogram of body
      weight) to achieve a defined blood flow reduction (0%-75%) from baseline levels
      at 60 minutes, as determined with correlative laser Doppler flowmetry. The mean
      blood flow was calculated for each of four 5-mm sections that covered the entire
      tumor, as well as for the entire tumor after multiple sections were processed.
      Measurements obtained with both methods were correlated with laser Doppler
      flowmetry measurements. Interobserver agreement was determined for two blinded
      radiologists, who calculated the percentage of blood flow reduction for the "most
      representative" single sections at baseline and after arsenic administration.
      These results were compared with the interobserver variability of the same
      radiologists obtained by summing blood flow changes for the entire tumor volume.
      RESULTS: Overall correlations for acute blood flow reduction were demonstrated
      between laser Doppler flowmetry and the two CT perfusion approaches (single
      section CT, r=0.85 and r(2)=0.73; multisection CT, r=0.93 and r(2)=0.87; pooled
      data, P=.01). CT perfusion disclosed marked heterogeneity of blood flow, with
      variations of 36% +/- 13 between adjacent 5-mm sections. Given these marked
      differences, interobserver agreement was much lower for single-section CT
      (standard deviation, 0.22) than for multisection CT (standard deviation, 0.10;
      P=.01). CONCLUSION: Multisection CT perfusion techniques may provide an accurate
      and more reproducible method of tumor perfusion surveillance than comparison of
      single representative tumor sections.

PMID- 17517931
TI  - Advanced hepatocellular carcinoma: CT perfusion of liver and tumor tissue-
      initial experience.
AB  - PURPOSE: To prospectively assess computed tomographic (CT) perfusion for
      evaluation of tumor vascularity of advanced hepatocellular carcinoma (HCC) and to
      correlate CT perfusion parameters with tumor grade and serum markers. MATERIALS
      AND METHODS: The study was HIPAA compliant and was approved by the institutional
      review board. Patients provided informed consent. Thirty patients (22 men, eight
      women; mean age, 60 years; range, 28-79 years) with unresectable or metastatic
      HCC were studied. Dynamic first-pass CT perfusion was performed in primary (n=25)
      and metastatic (n=5) HCCs after intravenous injection of contrast medium. Data
      were analyzed to calculate tissue blood flow, blood volume, mean transit time,
      and permeability-surface area product. Repeat examination was performed in four
      patients within 30 hours to test reproducibility of CT perfusion. CT perfusion
      parameters were compared among tumors of different grades, with presence or
      absence of portal vein invasion, with presence or absence of cirrhosis, and of
      various extrahepatic metastases. Parameters were correlated with HCC serum
      markers. One-way analysis of variance was used to calculate variations in CT
      perfusion parameters. RESULTS: Good correlation (r=0.9, P<.01) was observed
      between repeat examination results and first CT examination results. There was a
      significant difference (P <or= .05) in CT perfusion parameters between primary
      HCC and background liver parenchyma. Well-differentiated HCC showed significantly
      higher perfusion values (P <or= .05) than other grades. There was no significant
      difference in tumor perfusion between presence or absence of portal vein invasion
      or cirrhosis. Lymph node metastasis demonstrated lower values compared with
      metastases from other extrahepatic sites. There was no significant correlation
      between CT perfusion parameters and serum markers. CONCLUSION: Results suggest
      that CT perfusion is a feasible and, from the limited data, reproducible
      technique for quantifying tumor vascularity and angiogenesis in advanced HCC.

PMID- 17517932
TI  - Comparison of delayed enhanced CT and chemical shift MR for evaluating
      hyperattenuating incidental adrenal masses.
AB  - PURPOSE: To retrospectively compare the accuracy of delayed enhanced computed
      tomography (CT) and chemical shift magnetic resonance (MR) imaging for
      characterizing hyperattenuating adrenal masses at CT, with either follow-up
      imaging or pathologic review as the reference standard. MATERIALS AND METHODS:
      The institutional review board approved this retrospective study with a waiver of
      patient informed consent. Forty-three hyperattenuating adrenal masses (>10 HU) on
      unenhanced CT images were found in 34 patients (23 men and 11 women; mean age,
      52.7 years) by reviewing radiologic reports. These lesions were retrospectively
      analyzed with delayed enhanced CT and chemical shift MR. The diagnostic accuracy
      of CT by using absolute percentage loss of enhancement (PLE) and relative PLE and
      of chemical shift MR by using adrenal-to-spleen ratio (ASR) or signal intensity
      index (SII) were obtained to determine which modality was more accurate for lipid
      poor adenoma. For CT, an adenoma was diagnosed if a mass had an absolute PLE
      greater than 60% and a relative PLE greater than 40%. For MR, an adenoma was
      diagnosed if a mass had an ASR of 0.71 or an SII greater than 16.5%. McNemar test
      was used to compare diagnostic performance of CT and MR. RESULTS:
      Hyperattenuating adrenal masses included 37 adenomas and six nonadenomas. The
      sensitivity, specificity, and accuracy for adenoma at CT were 97% (36 of 37),
      100% (six of six), and 98% (42 of 43), respectively, and at MR were 86% (32 of
      37), 50% (three of six), and 49% (21 of 43), respectively. CT helped confirm five
      more adenomas and three more metastatic tumors than did MR. However, there was no
      significant difference for diagnostic accuracy between these two imaging
      modalities (P>.05) CONCLUSION: Delayed enhanced CT can characterize additional
      hyperattenuating adrenal masses that cannot be characterized with chemical shift
      MR.

PMID- 17517933
TI  - Assessment of detective quantum efficiency: intercomparison of a recently
      introduced international standard with prior methods.
AB  - PURPOSE: To prospectively evaluate the recently introduced international standard
      method for measurement of the detective quantum efficiency (DQE) of digital
      radiography systems, in comparison with representative prior methods. MATERIALS
      AND METHODS: A recently introduced international standard method (International
      Electrotechnical Commission [IEC] 62220-1, 2003) for DQE measurement and two
      previously described DQE evaluation methods were considered. In addition to an
      overall comparison, evaluations of the following method factors were performed:
      beam quality, beam-limiting devices (apertures or collimators), noise power
      spectrum (NPS) analysis algorithms and parameters (area, region of interest size,
      background detrending), and modulation transfer function (MTF) test devices and
      methods. RESULTS: Overall, at low to middle frequencies, the IEC method yielded
      DQE estimates that were 3.3% and 6.5% lower than the values yielded by the two
      previous methods. Averaged over the frequency range of 1.5-2.5 mm(-1), the DQE
      estimate derived by using the IEC method was 7.1% lower and 12.4% higher than the
      estimates derived by using the other two methods. Results obtained with the two
      previous DQE evaluation methods agreed well (within 2.0%) in the low- to middle
      frequency range but diverged by up to 10% at higher frequencies. When the DQE
      method factors were evaluated separately, the largest percentage deviations in
      DQE were associated with (in order of decreasing influence) the MTF analysis
      method ( approximately 11%), the beam limitation (about 7%-10%), the beam quality
      ( approximately 9%), and the NPS analysis method ( approximately 3%). CONCLUSION:
      Comparison of DQE estimates obtained by using the recently introduced
      international standard technique with those obtained by using prior methods
      revealed that the overall measurement method can affect the DQE estimate by as
      much as 12%. Findings further suggest that both beam limitation achieved by means
      of internal collimation (rather than external apertures) and use of a radio
      opaque edge MTF device yield a more accurate estimation of the DQE.

PMID- 17517934
TI  - Low spin-lock field T1 relaxation in the rotating frame as a sensitive MR imaging
      marker for gene therapy treatment response in rat glioma.
AB  - PURPOSE: To prospectively assess the effectiveness of T1 relaxation in the
      rotating frame (T1 rho) dispersion and the low spin-lock radiofrequency field
      (B(1)) T1 rho magnetic resonance (MR) imaging relaxation time in noninvasive
      monitoring of gene therapy response in BT4C glioma in rats. MATERIALS AND
      METHODS: All animal studies were approved by the ethical committee of the
      National Laboratory Animal Center. Rats with BT4C gliomas (n=9) were treated with
      herpes simplex virus thymidine kinase gene therapy and were compared with
      untreated rats (n=5). Absolute T1 rho at a B(1) range of 2.0 x 10(-6) to 1.4 x
      10(-4) T, T1, T2, and apparent diffusion constant were measured at 4.7 T during
      treatment. Statistical significance was tested by using repeated-measures
      analysis of variance. RESULTS: A significant (P<.05) lengthening of T1 rho was
      observed beginning on the 4th day of treatment, and T1 rho values increased to be
      approximately 80% higher than values observed before treatment. These changes
      preceded T1 and T2 changes and resembled those of water diffusion. The T1 rho was
      associated with a treatment-induced decrease in cell density; this was the only
      measured MR imaging property that provided significant (P<.05) Pearson
      correlation with cell density in the tumor border. T1 rho relaxation dispersion,
      however, did not offer additional benefits over those offered in one B(1)
      experiment in the early phase of treatment. CONCLUSION: T1 rho with low B(1) is
      an excellent MR imaging marker of early gene therapy response in gliomas. The low
      B(1) approach is not limited by specific absorption rate restrictions; this
      finding suggests that spin-lock methods could be applicable in clinical settings.
      (

PMID- 17517935
TI  - Complications of diagnostic cerebral angiography: evaluation of 19,826
      consecutive patients.
AB  - PURPOSE: To retrospectively evaluate the complications of diagnostic cerebral
      catheter angiography in 19,826 consecutive patients. MATERIALS AND METHODS: This
      HIPAA-compliant study had institutional review board approval, with waiver of
      informed consent. Demographic, procedural, and complication data in 19 826
      consecutive patients undergoing diagnostic cerebral angiography at one
      institution from 1981 through 2003 were retrospectively reviewed. Neurologic,
      systemic, and local complications were recorded on the basis of clinical follow
      up results after each angiographic examination. Events that occurred within 24
      hours of angiography were considered to be complications of the procedure.
      Multivariable analysis was employed to identify patient and procedural factors
      significantly associated with neurologic complications. RESULTS: Neurologic
      complications occurred in 522 examinations (2.63%), and 27 of these (0.14%) were
      strokes with permanent disability. Twelve deaths occurred (0.06%). Access-site
      hematoma was the most common complication overall (4.2%). Factors independently
      associated with an increased risk of neurologic complication included the
      indication of atherosclerotic cerebrovascular disease (odds ratio [OR], 2.494),
      the indication of subarachnoid hemorrhage (OR, 2.523), and the comorbidity of
      frequent transient ischemic attack (OR, 1.674). Factors independently associated
      with a decreased risk of neurologic complication were increasing chronologic year
      in which the procedure was performed (OR, 0.659 per 5-year interval) and
      involvement of a trainee in the procedure (OR, 0.710). CONCLUSION: In this
      review, diagnostic catheter cerebral angiography was found to have relatively low
      complication rates.

PMID- 17517936
TI  - Localizing and lateralizing language in patients with brain tumors: feasibility
      of routine preoperative functional MR imaging in 81 consecutive patients.
AB  - PURPOSE: To prospectively assess the feasibility of standardized presurgical
      functional magnetic resonance (MR) imaging for localizing the Broca and Wernicke
      areas and for lateralizing language function. MATERIALS AND METHODS: The study
      was approved by the responsible ethics commission, and patients gave written
      informed consent. Eighty-one patients (36 female and 45 male patients; age range,
      7-75 years) with different brain tumors underwent blood oxygen level-dependent
      functional MR imaging at 1.5 T with two paradigms: sentence generation (SG) and
      word generation (WG). Functional MR imaging measurements, data processing, and
      evaluation were fully standardized by using dedicated software. Four regions of
      interest were evaluated in each patient: the Broca and Wernicke areas and their
      anatomic homologues in the right hemisphere. Statistics were calculated. RESULTS:
      The SG and WG paradigms were successfully completed by all (100%) and 70 (86%)
      patients, respectively. Success rates in localizing and lateralizing language
      were 96% for the Broca and Wernicke areas with the SG paradigm, 81% for the Broca
      area and 80% for the Wernicke area with the WG paradigm, and 98% for both areas
      when the SG and WG paradigms were used in combination. Functional localizations
      were consistent for SG and WG paradigms in the inferior frontal gyrus (Broca
      area) and the superior temporal, supramarginal, and angular gyri (Wernicke area).
      Surgery was not performed in seven patients (9%) and was modified in two patients
      (2%) because of functional MR imaging findings. CONCLUSION: Functional MR imaging
      proved to be feasible during routine diagnostic neuroimaging for localizing and
      lateralizing language function preoperatively.

PMID- 17517937
TI  - Contrast-enhanced MR angiography of the chest and abdomen with use of controlled
      apnea in children.
AB  - PURPOSE: To retrospectively determine if controlled apnea improves the image
      quality of contrast material--enhanced magnetic resonance (MR) angiography of the
      chest and abdomen in children. MATERIALS AND METHODS: Institutional review board
      approval and waiver of informed consent were obtained for this HIPAA-compliant
      study. The authors evaluated contrast-enhanced MR angiographic procedures
      performed in the chest, abdomen, or both, in 23 children (14 boys, nine girls;
      age range, 1 month to 8 years) who were under general anesthesia. All patients
      underwent mechanical ventilation with preoxygenation (100% oxygen) prior to
      controlled apnea during image acquisition. In control subjects, the authors
      assessed contrast-enhanced MR angiographic procedures performed in the chest,
      abdomen, or both, in 23 children (matched for age and type of study with children
      in the controlled apnea group; 11 boys, 12 girls; age range, 1 month to 8 years)
      who were under general anesthesia (n=15) or deep sedation (n=8) and were
      breathing spontaneously during image acquisition. MR angiograms of the chest,
      abdomen, or both, were assessed for image quality, motion artifacts, and vessel
      definition by two radiologists working in consensus with a subjective grading
      scale. Wilcoxon signed rank test was used to assess differences in measurements.
      RESULTS: Image quality was rated excellent in 97% (30 of 31) of studies with
      controlled apnea and in 30% (nine of 31) of control studies (P<.001). Motion
      artifacts were absent in 97% (30 of 31) of studies with controlled apnea and 13%
      (four of 31) of control studies (P<.001). Vessel sharpness was rated as being
      significantly better on images obtained with controlled apnea (P<.05). There were
      no complications caused by anesthesia or sedation in either group. CONCLUSION:
      Controlled apnea is highly effective in children for eliminating respiratory
      motion artifacts with contrast-enhanced MR angiographic studies, resulting in
      greatly improved image quality and spatial resolution.

PMID- 17517938
TI  - Multidetector CT of the paranasal sinus: potential for radiation dose reduction.
AB  - The aim of the study was to retrospectively determine the potential for radiation
      dose reduction at multidetector computed tomography (CT) of the paranasal sinus
      by using computer simulation of the effect of low-radiation dose acquisition on
      diagnostic image quality. This HIPAA compliant study was approved by the
      institutional human research committee. The need for informed patient consent was
      waived. Twenty patients underwent four-section CT at 120 kV, 170 mAs, and 4 x 1
      mm collimation. Artificial image noise was added to the CT raw data by using a
      dedicated software platform. Acquisitions with effective tube currents of 134,
      100, 67, and 33 mAs were simulated. Each raw data set was reconstructed with bone
      and soft-tissue algorithms, and two radiologists independently rated the images
      in blinded fashion. A two-sided paired Student t test was used for statistical
      analysis. The lowest radiation dose that still provided diagnostic quality was
      <or=67 effective mAs for osseous structures and <or=134 effective mAs for the
      optic nerve and the inferior rectus muscle. On the basis of the results, tube
      currents can be lowered and radiation dose reduced by 20%.

PMID- 17517939
TI  - Virtual autopsy: two- and three-dimensional multidetector CT findings in drowning
      with autopsy comparison.
AB  - PURPOSE: To retrospectively determine the multidetector computed tomographic (CT)
      virtual autopsy findings of death by drowning in comparison with autopsy
      findings. MATERIALS AND METHODS: The institutional review board of the Armed
      Forces Institute of Pathology approved this HIPAA-compliant study and did not
      require informed consent by the next of kin. Total-body multidetector CT was
      performed, immediately prior to routine autopsy, in 28 consecutive male subjects
      (mean age, 24.2 years) who died of drowning and a control group of 12 consecutive
      male subjects (mean age, 50.8 years) who died of sudden death from
      atherosclerotic coronary artery disease. Images were evaluated for the presence
      of fluid and sediment in the paranasal sinuses and airways, mastoid air cell
      fluid, frothy fluid in the airways, pulmonary opacity (ground-glass opacity or
      airspace consolidation), interlobular septal thickening, and gastric distention
      and contents (fluid or sediment). Image findings were compared with findings from
      autopsy reports and photographs. RESULTS: All drowning subjects had fluid in the
      paranasal sinuses and mastoid air cells and had ground-glass opacity within the
      lungs. Twenty-six subjects (93%) had fluid in the subglottic trachea and main
      bronchi. Fourteen subjects (50%) had high-attenuation sediment in the subglottic
      airways. Frothy fluid in the airways was present in six subjects (21%). Twenty
      five (89%) of the drowning subjects had pulmonary ground-glass opacity with
      septal lines, which was mild with apical and perihilar distribution in 12
      subjects, severe and diffuse in nine, posterior and basilar in three, and limited
      to the apices in one (not assessed in three of 28 subjects because of
      decomposition). Control subjects showed mastoid cell fluid (25%), sinus fluid
      (83%), subglottic airway fluid (92%), and pulmonary ground-glass opacity (100%)
      but did not have evidence of frothy airway fluid or high-attenuation sediment in
      the airways. CONCLUSION: The multidetector CT finding of frothy airway fluid or
      high-attenuation airway sediment is highly suggestive of drowning; multidetector
      CT findings of pan sinus fluid, mastoid cell fluid, subglottic tracheal and
      bronchial fluid, and ground-glass opacity within the lung at multidetector CT are
      supportive of drowning in the appropriate scenario.

PMID- 17517940
TI  - Percutaneous radiofrequency ablation of hepatic tumors against the diaphragm:
      frequency of diaphragmatic injury.
AB  - PURPOSE: To retrospectively determine the frequency of diaphragmatic injury when
      percutaneous hepatic radiofrequency (RF) ablation is performed adjacent to the
      diaphragm. MATERIALS AND METHODS: Institutional Review Board approval was
      obtained for our HIPAA-compliant study. Informed consent for the ablation
      procedure and for use of related data for future research was obtained from each
      patient. A retrospective review was conducted of 215 patients undergoing
      percutaneous RF ablation of hepatic tumors. Twenty-nine patients (21 men and
      eight women; age, 41-89 years) were identified with tumors abutting the
      diaphragm. Episodes of right shoulder pain were recorded. A panel of radiologists
      blinded to the patients' clinical histories reviewed their imaging for evidence
      of diaphragmatic injury and ablation success. A generalized estimating equation
      model and the Fisher exact test were used for statistical analysis. RESULTS: The
      29 patients had a total of 33 tumors abutting the diaphragm. Tumor size was 1.3
      5.5 cm (mean, 3.2 cm +/- 1.1). After ablation, five (17%) patients reported right
      shoulder pain. In four, pain was mild or moderate, with symptoms lasting 2-14
      days (median, 5.5 days). Three of these showed diaphragmatic thickening on
      postablation computed tomographic (CT) scans. One patient had severe pain lasting
      2 weeks, followed by milder pain for 2 months. This patient's postablation CT
      images showed focal nodular diaphragmatic thickening. This patient was treated
      with a multitined device; the other four, with straight-needle devices. Local
      tumor progression was seen in 14 tumors (42.4%). Tumors 3 cm or smaller had a
      much lower local progression rate than tumors larger than 3 cm (12.5% vs 70.6%).
      CONCLUSION: Of 29 patients who had ablation of hepatic tumors adjacent to the
      diaphragm, five (17%) had diaphragmatic injury, which was clinically apparent
      with right shoulder pain.

PMID- 17517943
TI  - Case 114: radical trachelectomy.

PMID- 17517944
TI  - Case 115: aortic pseudoaneurysm from penetrating superior vena cava stent.

PMID- 17517945
TI  - The crazy-paving sign.

PMID- 17517946
TI  - Assessment of lung cancer perfusion by using Patlak analysis: what do we measure?

PMID- 17517947
TI  - Measurement of signal-to-noise ratio in MR imaging with sensitivity encoding.

PMID- 17517948
TI  - Blood flow quantification with permeable contrast agents: a valid technique?

PMID- 17517949
TI  - Randomized controlled trial of pyrimethamine plus sulfadiazine versus
      trimethoprim plus sulfamethoxazole for treatment of toxoplasmic encephalitis in
      AIDS patients.
AB  - BACKGROUND: Toxoplasmic encephalitis (TE), caused by Toxoplasma gondii, is common
      in AIDS patients. TE can result in tissue destruction via massive inflammation
      and brain abscess formation. METHODS: Randomized controlled trials were performed
      in AIDS patients to assess which drug regimen was optimally effective for the
      treatment of TE. AIDS patients with TE were randomly divided into 3 groups that
      received a 6-week course of either pyrimethamine (50 mg/day or 100 mg/day) plus
      sulfadiazine (4 g/day) and folinic acid (25 mg/day) or trimethoprim (10
      mg/kg/day) plus sulfamethoxazole (50 mg/kg/day) (TMP-SMX), and results were
      evaluated with respect to clinical response, mortality, morbidity, and serious
      adverse events. The primary outcome was defined as death in the first 6-week
      period. The secondary outcome was successful treatment within 6 weeks without
      severe adverse events, bone marrow suppression, drug-induced rash, or any other
      event that caused a change in the treatment regimen. RESULTS: The results from
      this study showed that in AIDS patients, TE was most successfully treated with
      the combination of pyrimethamine (50 mg/day) plus sulfadiazidine (4 g/day) and
      folinic acid (25 mg/day); failure rates were not significantly different among
      the 3 treatment groups. CONCLUSIONS: Available data suggest that of the currently
      available options, treatment of TE with pyrimethamine at 50 mg/day plus
      sulfadiazidine at 4 g/day provides the best primary outcome for AIDS patients
      with TE; however, because this study was terminated prematurely, we suggest that
      treatment with intravenous TMP-SMX be further evaluated to determine its
      efficacy.

PMID- 17517958
TI  - Ira Mellman: from endosomes to industry. Interview by William A Wells.
AB  - Disease-related research requires a different kind of teamwork, says Ira Mellman.
      He hopes to find that team at his new home at Genentech.

PMID- 17517959
TI  - Intranucleolar sites of ribosome biogenesis defined by the localization of early
      binding ribosomal proteins.
AB  - Considerable efforts are being undertaken to elucidate the processes of ribosome
      biogenesis. Although various preribosomal RNP complexes have been isolated and
      molecularly characterized, the order of ribosomal protein (r-protein) addition to
      the emerging ribosome subunits is largely unknown. Furthermore, the correlation
      between the ribosome assembly pathway and the structural organization of the
      dedicated ribosome factory, the nucleolus, is not well established. We have
      analyzed the nucleolar localization of several early binding r-proteins in human
      cells, applying various methods, including live-cell imaging and electron
      microscopy. We have located all examined r-proteins (S4, S6, S7, S9, S14, and L4)
      in the granular component (GC), which is the nucleolar region where later pre
      ribosomal RNA (rRNA) processing steps take place. These results imply that early
      binding r-proteins do not assemble with nascent pre-rRNA transcripts in the dense
      fibrillar component (DFC), as is generally believed, and provide a link between r
      protein assembly and the emergence of distinct granules at the DFC-GC interface.

PMID- 17517960
TI  - Chemoattractants and chemorepellents act by inducing opposite polarity in
      phospholipase C and PI3-kinase signaling.
AB  - During embryonic development, cell movement is orchestrated by a multitude of
      attractants and repellents. Chemoattractants applied as a gradient, such as cAMP
      with Dictyostelium discoideum or fMLP with neutrophils, induce the activation of
      phospholipase C (PLC) and phosphoinositide 3 (PI3)-kinase at the front of the
      cell, leading to the localized depletion of phosphatidylinositol 4,5-bisphosphate
      (PI[4,5]P(2)) and the accumulation of phosphatidylinositol-3,4,5-trisphosphate
      (PI[3,4,5]P(3)). Using D. discoideum, we show that chemorepellent cAMP analogues
      induce localized inhibition of PLC, thereby reversing the polarity of
      PI(4,5)P(2). This leads to the accumulation of PI(3,4,5)P(3) at the rear of the
      cell, and chemotaxis occurs away from the source. We conclude that a PLC polarity
      switch controls the response to attractants and repellents.

PMID- 17517961
TI  - BimS-induced apoptosis requires mitochondrial localization but not interaction
      with anti-apoptotic Bcl-2 proteins.
AB  - Release of apoptogenic proteins such as cytochrome c from mitochondria is
      regulated by pro- and anti-apoptotic Bcl-2 family proteins, with pro-apoptotic
      BH3-only proteins activating Bax and Bak. Current models assume that apoptosis
      induction occurs via the binding and inactivation of anti-apoptotic Bcl-2
      proteins by BH3-only proteins or by direct binding to Bax. Here, we analyze
      apoptosis induction by the BH3-only protein Bim(S). Regulated expression of
      Bim(S) in epithelial cells was followed by its rapid mitochondrial translocation
      and mitochondrial membrane insertion in the absence of detectable binding to anti
      apoptotic Bcl-2 proteins. This caused mitochondrial recruitment and activation of
      Bax and apoptosis. Mutational analysis of Bim(S) showed that mitochondrial
      targeting, but not binding to Bcl-2 or Mcl-1, was required for apoptosis
      induction. In yeast, Bim(S) enhanced the killing activity of Bax in the absence
      of anti-apoptotic Bcl-2 proteins. Thus, cell death induction by a BH3-only
      protein can occur through a process that is independent of anti-apoptotic Bcl-2
      proteins but requires mitochondrial targeting.

PMID- 17517962
TI  - Myosin V, Rab11, and dRip11 direct apical secretion and cellular morphogenesis in
      developing Drosophila photoreceptors.
AB  - Sensory neuron terminal differentiation tasks apical secretory transport with
      delivery of abundant biosynthetic traffic to the growing sensory membrane. We
      recently showed Drosophila Rab11 is essential for rhodopsin transport in
      developing photoreceptors and asked here if myosin V and the Drosophila Rab11
      interacting protein, dRip11, also participate in secretory transport. Reduction
      of either protein impaired rhodopsin transport, stunting rhabdomere growth and
      promoting accumulation of cytoplasmic rhodopsin. MyoV-reduced photoreceptors also
      developed ectopic rhabdomeres inappropriately located in basolateral membrane,
      indicating a role for MyoV in photoreceptor polarity. Binary yeast two hybrids
      and in vitro protein-protein interaction predict a ternary complex assembled by
      independent dRip11 and MyoV binding to Rab11. We propose this complex delivers
      morphogenic secretory traffic along polarized actin filaments of the subcortical
      terminal web to the exocytic plasma membrane target, the rhabdomere base. A
      protein trio conserved across eukaryotes thus mediates normal, in vivo sensory
      neuron morphogenesis.

PMID- 17517963
TI  - Caveolin-1 regulates cell polarization and directional migration through Src
      kinase and Rho GTPases.
AB  - Development, angiogenesis, wound healing, and metastasis all involve the movement
      of cells in response to changes in the extracellular environment. To determine
      whether caveolin-1 plays a role in cell migration, we have used fibroblasts from
      knockout mice. Caveolin-1-deficient cells lose normal cell polarity, exhibit
      impaired wound healing, and have decreased Rho and increased Rac and Cdc42 GTPase
      activities. Directional persistency of migration is lost, and the cells show an
      impaired response to external directional stimuli. Both Src inactivation and
      p190RhoGAP knockdown restore the wild-type phenotype to caveolin-1-deficient
      cells, suggesting that caveolin-1 stimulates normal Rho GTP loading through
      inactivation of the Src-p190RhoGAP pathway. These findings highlight the
      importance of caveolin-1 in the establishment of cell polarity during directional
      migration through coordination of the signaling of Src kinase and Rho GTPases.

PMID- 17517964
TI  - GPI-anchored receptor clusters transiently recruit Lyn and G alpha for temporary
      cluster immobilization and Lyn activation: single-molecule tracking study 1.
AB  - The signaling mechanisms for glycosylphosphatidylinositol-anchored receptors (GPI
      ARs) have been investigated by tracking single molecules in living cells. Upon
      the engagement or colloidal gold-induced cross-linking of CD59 (and other GPI
      ARs) at physiological levels, CD59 clusters containing three to nine CD59
      molecules were formed, and single molecules of Galphai2 or Lyn (GFP conjugates)
      exhibited the frequent but transient (133 and 200 ms, respectively) recruitment
      to CD59 clusters, via both protein-protein and lipid-lipid (raft) interactions.
      Each CD59 cluster undergoes alternating periods of actin-dependent temporary
      immobilization (0.57-s lifetime; stimulation-induced temporary arrest of lateral
      diffusion [STALL], inducing IP(3) production) and slow diffusion (1.2 s). STALL
      of a CD59 cluster was induced right after the recruitment of Galphai2. Because
      both Galphai2 and Lyn are required for the STALL, and because Lyn is
      constitutively recruited to CD59 clusters, the STALL of CD59 clusters is likely
      induced by the Galphai2 binding to, and its subsequent activation of, Lyn within
      the same CD59 cluster.

PMID- 17517965
TI  - Dynamic recruitment of phospholipase C gamma at transiently immobilized GPI
      anchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking
      study 2.
AB  - Clusters of CD59, a glycosylphosphatidylinositol-anchored receptor (GPI-AR), with
      physiological sizes of approximately six CD59 molecules, recruit Galphai2 and Lyn
      via protein-protein and raft interactions. Lyn is activated probably by the
      Galphai2 binding in the same CD59 cluster, inducing the CD59 cluster's binding to
      F-actin, resulting in its immobilization, termed stimulation-induced temporary
      arrest of lateral diffusion (STALL; with a 0.57-s lifetime, occurring
      approximately every 2 s). Simultaneous single-molecule tracking of GFP-PLCgamma2
      and CD59 clusters revealed that PLCgamma2 molecules are transiently (median =
      0.25 s) recruited from the cytoplasm exclusively at the CD59 clusters undergoing
      STALL, producing the IP(3)-Ca(2+) signal. Therefore, we propose that the CD59
      cluster in STALL may be a key, albeit transient, platform for transducing the
      extracellular GPI-AR signal to the intracellular IP(3)-Ca(2+) signal, via
      PLCgamma2 recruitment. The prolonged, analogue, bulk IP(3)-Ca(2+) signal, which
      lasts for more than several minutes, is likely generated by the sum of the short
      lived, digital-like IP(3) bursts, each created by the transient recruitment of
      PLCgamma2 molecules to STALLed CD59.

PMID- 17517966
TI  - Mice lacking NKCC1 are protected from development of bacteremia and hypothermic
      sepsis secondary to bacterial pneumonia.
AB  - The contribution of the Na(+)-K(+)-Cl(-) transporter (NKCC1) to fluid in ion
      transport and fluid secretion in the lung and in other secretory epithelia has
      been well established. Far less is known concerning the role of this
      cotransporter in the physiological response of the pulmonary system during acute
      inflammation. Here we show that mice lacking this transporter are protected
      against hypothermic sepsis and bacteremia developing as a result of Klebsiella
      pneumoniae infection in the lung. In contrast, this protection was not observed
      in NKCC1(-/-) mice with K. pneumoniae-induced peritonitis. Although overall
      recruitment of cells to the lungs was not altered, the number of cells present in
      the airways was increased in the NKCC1(-/-) animals. Despite this robust
      inflammatory response, the increase in vascular permeability observed in this
      acute inflammatory model was attenuated in the NKCC1(-/-) animals. Our studies
      suggest that NKCC1 plays a unique and untoward unrecognized role in acute
      inflammatory responses in the lung and that specific inhibition of this NKCC
      isoform could be beneficial in treatment of sepsis.

PMID- 17517967
TI  - Increased susceptibility to colitis and colorectal tumors in mice lacking core 3
      derived O-glycans.
AB  - Altered intestinal O-glycan expression has been observed in patients with
      ulcerative colitis and colorectal cancer, but the role of this alteration in the
      etiology of these diseases is unknown. O-glycans in mucin core proteins are the
      predominant components of the intestinal mucus, which comprises part of the
      intestinal mucosal barrier. Core 3-derived O-glycans, which are one of the major
      types of O-glycans, are primarily expressed in the colon. To investigate the
      biological function of core 3-derived O-glycans, we engineered mice lacking core
      3 beta1,3-N-acetylglucosaminyltransferase (C3GnT), an enzyme predicted to be
      important in the synthesis of core 3-derived O-glycans. Disruption of the C3GnT
      gene eliminated core 3-derived O-glycans. C3GnT-deficient mice displayed a
      discrete, colon-specific reduction in Muc2 protein and increased permeability of
      the intestinal barrier. Moreover, these mice were highly susceptible to
      experimental triggers of colitis and colorectal adenocarcinoma. These data reveal
      a requirement for core 3-derived O-glycans in resistance to colonic disease.

PMID- 17517968
TI  - Th2-driven, allergen-induced airway inflammation is reduced after treatment with
      anti-Tim-3 antibody in vivo.
AB  - T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) is a surface
      molecule that is preferentially expressed on activated Th1 cells in comparison to
      Th2 cells. Blockade of Tim-3 has been shown to enhance Th1-driven pathology in
      vivo, suggesting that blockade of Tim-3 may improve the development of Th2
      associated responses such as allergy. To examine the effects of Tim-3 blockade on
      the Th2 response in vivo, we administered anti-Tim-3 antibody during pulmonary
      inflammation induced by transfer of ovalbumin (OVA)-reactive Th2 cells, and
      subsequent aerosol challenge with OVA. In this model, anti-Tim-3 antibody
      treatment before each airway challenge significantly reduced airway
      hyperreactivity, with a concomitant decrease in eosinophils and Th2 cells in the
      lung. We examined Th1 and Th2 cytokine levels in the lung after allergen
      challenge and found that pulmonary expression of the Th2 cytokine IL-5 was
      significantly reduced, whereas IFN-gamma levels were significantly increased by
      anti-Tim-3 antibody treatment. Thus, blocking Tim-3 function has a beneficial
      effect during pulmonary inflammation by skewing the Th2 response toward that of a
      Th1 type, suggesting an important role for Tim-3 in the regulation of allergic
      disease.

PMID- 17517969
TI  - G-CSF rescues the memory impairment of animal models of Alzheimer's disease.
AB  - Most of the current clinical treatments for Alzheimer's disease (AD) are largely
      symptomatic and can have serious side effects. We have tested the feasibility of
      using the granulocyte colony-stimulating factor (G-CSF), which is known to
      mobilize hematopoietic stem cells (HSCs) from the bone marrow into the peripheral
      blood, as a therapeutic agent for AD. Subcutaneous administration of G-CSF into
      two different beta-amyloid (Abeta)-induced AD mouse models substantially rescued
      their cognitive/memory functions. The rescue was accompanied by the accumulation
      of 5-bromo-2'deoxyuridine-positive HSCs, as well as local neurogenesis
      surrounding the Abeta aggregates. Furthermore, the level of acetylcholine in the
      brains of Tg2576 mice was considerably enhanced upon G-CSF treatment. We suggest
      that G-CSF, a drug already extensively used for treating chemotherapy-induced
      neutropenia, should be pursued as a novel, noninvasive therapeutic agent for the
      treatment of AD.

PMID- 17517970
TI  - Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin
      mycolactone.
AB  - Mycolactone is a polyketide toxin produced by Mycobacterium ulcerans (Mu), the
      causative agent of the skin disease Buruli ulcer (BU). Surprisingly, infected
      tissues lack inflammatory infiltrates. Structural similarities between
      mycolactone and immunosuppressive agents led us to investigate the
      immunomodulatory properties of mycolactone on dendritic cells (DCs), the key
      initiators and regulators of immune responses. At noncytotoxic concentrations,
      phenotypic and functional maturation of both mouse and human DCs was inhibited by
      mycolactone. Notably, mycolactone blocked the emigration of mouse-skin DCs to
      draining lymph nodes, as well as their maturation in vivo. In human peripheral
      blood-derived DCs, mycolactone inhibited the ability to activate allogeneic T
      cell priming and to produce inflammatory molecules. Interestingly, production of
      the cytokines interleukin (IL) 12, tumor necrosis factor alpha, and IL-6 was only
      marginally affected, whereas production of the chemokines macrophage inflammatory
      protein (MIP) 1alpha, MIP-1beta, regulated on activation, normal T cell expressed
      and secreted, interferon gamma-inducible protein 10, and monocyte chemoattractant
      protein 1 was abolished at nanomolar concentrations. Importantly, mycolactone
      endogenously expressed by Mu mediated similar inhibitory effects on beta
      chemokine production by DCs. In accordance with the histopathological features of
      BUs, our results suggest that bacterial production of mycolactone may limit both
      the initiation of primary immune responses and the recruitment of inflammatory
      cells to the infection site. Moreover, they highlight a potential interest in
      mycolactone as a novel immunosuppressive agent.

PMID- 17517971
TI  - Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking
      surface recognition domains.
AB  - Factor H (FH) is an abundant serum glycoprotein that regulates the alternative
      pathway of complement-preventing uncontrolled plasma C3 activation and
      nonspecific damage to host tissues. Age-related macular degeneration (AMD),
      atypical hemolytic uremic syndrome (aHUS), and membranoproliferative
      glomerulonephritis type II (MPGN2) are associated with polymorphisms or mutations
      in the FH gene (Cfh), suggesting the existence of a genotype-phenotype
      relationship. Although AMD and MPGN2 share pathological similarities with the
      accumulation of complement-containing debris within the eye and kidney,
      respectively, aHUS is characterized by renal endothelial injury. This
      pathological distinction was reflected in our Cfh association analysis, which
      demonstrated that although AMD and MPGN2 share a Cfh at-risk haplotype, the
      haplotype for aHUS was unique. FH-deficient mice have uncontrolled plasma C3
      activation and spontaneously develop MPGN2 but not aHUS. We show that these mice,
      transgenically expressing a mouse FH protein functionally equivalent to aHUS
      associated human FH mutants, regulate C3 activation in plasma and spontaneously
      develop aHUS but not MPGN2. These animals represent the first model of aHUS and
      provide in vivo evidence that effective plasma C3 regulation and the defective
      control of complement activation on renal endothelium are the critical events in
      the molecular pathogenesis of FH-associated aHUS.

PMID- 17517972
TI  - Depression in diabetes: the chicken or the egg?

PMID- 17517973
TI  - Scabies in children.
AB  - Scabies is a common dermatological problem managed by both paediatricians and
      dermatologists. It manifests itself in various forms in children and differs from
      that in adults in many ways. The treatment of scabies has developed with the
      evolution of new strategies and anti-ectoparasitic drugs. Drugs such as
      permethrin and ivermectin have revolutionised its treatment. The management of
      scabies not only includes prescribing the correct drugs but also educating
      patients about their application. Treatment failure can result from a variety of
      causes and must be managed appropriately.

PMID- 17517974
TI  - Whistle blowing in clinical diagnosis.

PMID- 17517976
TI  - Attention deficit or lack of attention?

PMID- 17517977
TI  - Drug therapy in the management of acute asthma.

PMID- 17517978
TI  - Green for danger! Intestinal malrotation and volvulus.

PMID- 17517979
TI  - Obesity and overweight: its prevention, identification, assessment and
      management.

PMID- 17517981
TI  - Provider views--and strategies--for price transparency.

PMID- 17517982
TI  - Heart scans hold intermediate promise. CT scans for calcium in the heart's
      arteries only benefit people in the gray zone of heart disease risk.

PMID- 17517983
TI  - A new way to control blood pressure. Inactivating renin, which is made by the
      kidneys, may open the door to better blood pressure.

PMID- 17517984
TI  - New tool refines heart risk prediction. Adding C-reactive protein and family
      history modernizes and improves the standard risk tool.

PMID- 17517985
TI  - What the latest diet trial really means. Any diet that helps you take in fewer
      calories will help you shed pounds.

PMID- 17517986
TI  - As the hammock swings.

PMID- 17517987
TI  - Ask the doctor. Is weight lifting safe if I have a stent?

PMID- 17517988
TI  - Ask the doctor. Can eye drops for glaucoma affect the heart?

PMID- 17517989
TI  - Bipolar disorder in children. Difficult to diagnose, important to treat.

PMID- 17517990
TI  - Thyroid deficiency and mental health.

PMID- 17517991
TI  - Depression in China: finding a translation.

PMID- 17517993
TI  - Addiction treatment, ready or not.

PMID- 17517992
TI  - Williams syndrome in Japan: the interplay of genetics and culture.

PMID- 17517994
TI  - How important is a good breakfast for children?

PMID- 17517995
TI  - New biological paramagnetic center: octahedrally coordinated nickel(III) in the
      methanogenic bacteria.
AB  - Methanobacterium bryantii was grown in medium supplemented with nickel-61, an
      isotope with a nuclear spin of 3/2. The appearance of nuclear hyperfine structure
      in the electron paramagnetic resonance spectrum of a cell extract identified a
      previously observed signal as nickel(III) in an environment of octahedral
      coordination with rhombic distortions.

PMID- 17517996
TI  - What's wrong with doctors.
AB  - Review of: Groopman, Jerome. How doctors think. (Boston: Houghton Mifflin, 2007).

PMID- 17517997
TI  - The Court and abortion: worse than you think.
AB  - Analysis of recent U.S. Supreme Court decisions on abortion.

PMID- 17517998
TI  - [Differences in the neurosurgical treatment in the United states and Japan].

PMID- 17517999
TI  - Notes on the female condom: experiences in Brazil.
AB  - A nationwide effort to introduce the female condom (FC) into public health
      services was undertaken in Brazil in 1998-99. To this end, the Ministry of Health
      sponsored a national research group of public health professionals, aided by
      local field workers and supervisors, to conduct a preparatory study at 20 sites
      in six cities. Clinic health workers were trained to conduct the study. Following
      an educational session, 2382 women volunteered to use the FC and to report their
      experiences at follow-up. Among those seen at 15 days, 1782 had used the FC at
      least once; among those seen at the 90-day follow-up, 1453 women had used it at
      least once, while 1296 of them liked it and wished to continue its use. Among
      these 1296 women, barrier use at last intercourse (either with a male or a female
      condom) was more than double at 90 days what it had been at baseline: 70%
      compared with 33%. Clinics providing active health-education activities achieved
      higher rates of follow-up and of FC acceptability. These findings suggest that in
      Brazil, the introduction of the FC at public health centres could lead to high
      initial adoption rates and that continued use would be effective in encouraging
      safer sex. The level of health education and type of clinic are likely to
      influence the effectiveness of a future programme.

PMID- 17518000
TI  - The Primary Care Electronic Library: RSS feeds using SNOMED-CT indexing for
      dynamic content delivery.
AB  - BACKGROUND: Rich Site Summary (RSS) feeds are a method for disseminating and
      syndicating the contents of a website using extensible mark-up language (XML).
      The Primary Care Electronic Library (PCEL) distributes recent additions to the
      site in the form of an RSS feed. When new resources are added to PCEL, they are
      manually assigned medical subject headings (MeSH terms), which are then
      automatically mapped to SNOMED-CT terms using the Unified Medical Language System
      (UMLS) Metathesaurus. The library is thus searchable using MeSH or SNOMED-CT. Our
      syndicate partner wished to have remote access to PCEL coronary heart disease
      (CHD) information resources based on SNOMED-CT search terms. OBJECTIVE: To pilot
      the supply of relevant information resources in response to clinically coded
      requests, using RSS syndication for transmission between web servers. METHOD: Our
      syndicate partner provided a list of CHD SNOMED-CT terms to its end-users, a list
      which was coded according to UMLS specifications. When the end-user requested
      relevant information resources, this request was relayed from our syndicate
      partner's web server to the PCEL web server. The relevant resources were
      retrieved from the PCEL MySQL database. This database is accessed using a server
      side scripting language (PHP), which enables the production of dynamic RSS feeds
      on the basis of Source Asserted Identifiers (CODEs) contained in UMLS. RESULTS:
      Retrieving resources using SNOMED-CT terms using syndication can be used to build
      a functioning application. The process from request to display of syndicated
      resources took less than one second. CONCLUSION: The results of the pilot
      illustrate that it is possible to exchange data between servers using RSS
      syndication. This method could be utilised dynamically to supply digital library
      resources to a clinical system with SNOMED-CT data used as the standard of
      reference.

PMID- 17518001
TI  - [A giant uterine fibromyoma].

PMID- 17518002
TI  - [Giant pointed condyloma].

PMID- 17518003
TI  - [A perforating wound of the urinary bladder and rectum].

PMID- 17518004
TI  - [125 years since the first successful resection of the stomach].

PMID- 17518005
TI  - Pediatric urology.

PMID- 17518006
TI  - Transarterial chemoembolization for liver cancer.

PMID- 17518007
TI  - Importance of documentation to successful medication therapy management
      practices.

PMID- 17518008
TI  - Does sleep apnea change over time in patients with acute myocardial infarction?

PMID- 17518009
TI  - Transforming a payer-provider relationship from conflict to collaboration.
AB  - The current relationship between payers and providers is often adversarial. The
      growth of managed care has fostered very little cooperation between the payer and
      provider, even though both are working toward improved patient outcomes. This
      article describes the process by which a payer and provider were able to
      transform a contentious relationship into a collaborative patient-centered
      program. The program demonstrates that through the sharing of retrospective
      utilization data, improved clinical and financial outcomes can be achieved.

PMID- 17518010
TI  - Medication reconciliation: a necessity in promoting a safe hospital discharge.
AB  - Medication errors are among the most common type of patient-safety error and
      therefore are a priority for organizational performance-improvement efforts.
      Medication reconciliation has been found to greatly reduce adverse drug and
      medication events. At one facility, a computer-generated Physician Discharge
      Medication Worksheet (PDMW) was developed to aid medication reconciliation. Use
      of this tool led to a reduction in discrepancies in drug frequency and dose, as
      well as therapeutic duplication, at the time of discharge. Through the use of the
      PDMW, medication reconciliation has been dramatically improved.

PMID- 17518011
TI  - Lessons learned from performance feedback by a quality improvement organization.
AB  - Performance feedback is a common quality improvement (QI) intervention strategy
      in the outpatient setting. This article describes the use by one quality
      improvement organization (QIO) of performance feedback to primary-care physicians
      with claims-based measures relating to diabetes, adult vaccinations, and
      mammography screening. Feedback from the physicians identified themes relating to
      data accuracy, methodology of the feedback reports, reasons for low performance
      rates, and suggestions on how the QIO could improve its intervention strategy.
      The article highlights the value of collecting and analyzing formative data on
      the process and offers specific recommendations to other QI professionals
      contemplating the use of claims data for performance feedback.

PMID- 17518012
TI  - Health disparities in 30 indicators of recommended clinical care.
AB  - This article examines variations in clinical practice for 30 clinical indicators.
      Patients' age, gender, and morbidity and certain characteristics of their
      physicians affected whether they received recommended care. Recommended care
      increased with patient age for 13 significant clinical indicators and decreased
      with age for 7 others. Males received recommended care more often for 12 of 13
      clinical indicators. Recommended care varied by physician specialties for health
      screenings, disease management, and medication use. Patients seeing physicians
      who treated a high volume of patients generally received better care. The
      variations in recommended care suggest potential targets for healthcare quality
      improvements.

PMID- 17518013
TI  - Constructing adolescent substance abuse performance measures using administrative
      data.
AB  - Substance abuse among adolescents requires early intervention and proper
      treatment. Although substance use among this age group is considerable, the
      population of adolescents identified as having a substance use problem is
      significantly lower. Recent attention has focused on the use of adult substance
      abuse performance measures for quality improvement in this area. This article
      discusses the importance of performance measures for adolescent substance abuse
      treatment, the measurement tools now being developed, and implications for future
      treatment.

PMID- 17518014
TI  - Improving behavioral health satisfaction assessment: measuring patients'
      perceptions.
AB  - In order to focus on and improve key aspects of patient satisfaction in its
      behavioral health programs, Catholic Health East (CHE) enhanced its measurement
      methodology. In an effort to be consistent with the federal government's movement
      from measuring patient advocacy programs to measuring patients' perceptions, CHE
      transitioned to behavior-based questions. These questions give clear targets for
      program goals and initiatives by objectively measuring whether certain events and
      desired staff behaviors occurred during treatment, rather than subjectively
      ranking attributes of institution-defined service. Through this change in
      approach, CHE may better align its care and services with patients' wants and
      needs, as illustrated by four case examples.

PMID- 17518015
TI  - A wound-care process model improves emergency department turnaround time.
AB  - Numerous studies demonstrate that patient satisfaction correlates with perceived
      timeliness of care. Turnaround time data identified Laceration patients as a
      subset of emergency department patients who were not receiving high-quality care.
      With the Define-Measure-Analyze- Devise-Verify methodology, root causes of delay
      in operations were sought, and remedies were devised. An education module and an
      improved patient-care process model were implemented. Through the use of
      continuous quality improvement, a wound-care process model improved turnaround
      times for laceration care by 30 minutes.

PMID- 17518016
TI  - A rural healthcare quality agenda.

PMID- 17518017
TI  - Coordination of care--Minnesota's journey.

PMID- 17518018
TI  - The rural community--key to quality healthcare.

PMID- 17518019
TI  - Pennsylvania Critical Access Hospital Consortium: a strategy-focused performance
      improvement network.
AB  - The Pennsylvania Critical Access Hospital Consortium (PACAHC) has had success
      with an ambitious plan to bring together 12 small rural hospitals to support
      performance improvement initiatives. PACAHC differs from most other rural health
      networks or state Rural Hospital Flexibility (Flex) Programs because of its
      multiyear process to implement Balanced Scorecards at every member hospital and
      its innovative coordination of data collection and reporting systems to enable
      performance comparison. PACAHC also convenes statewide performance improvement
      meetings that allow partner organizations, such as the state quality improvement
      organization, to contribute to improvement activities.

PMID- 17518020
TI  - Rural communities improving quality through collaboration: the MaineHealth story.
AB  - Small and rural communities face unique challenges in improving healthcare
      quality. To address these challenges, MaineHealth, an integrated health system
      serving small and rural communities, leveraged knowledge, resources, and data
      through collaboration to help providers improve care and outcomes for asthma,
      heart failure, diabetes, and depression. The programs emphasized patient self
      care, used uniform clinical standards, and supported population-based data
      collection. This collaborative approach provided an effective way to achieve
      improved outcomes across a geographically and structurally diverse system, and it
      can help influence improvement efforts in other small and medium-sized rural
      communities.

PMID- 17518021
TI  - Metrics help rural hospitals achieve world-class performance.
AB  - This article describes the emerging trend of using metrics in rural hospitals to
      achieve world-class performance. This trend is a response to the fact that rural
      hospitals have small patient volumes yet must maintain a profit margin in order
      to fulfill their mission to the community. The conceptual idea for this article
      is based largely on Robert Kaplan and David Norton's Balanced Scorecard articles
      in the Harvard Business Review. The ideas also come from the experiences of the
      60-plus rural hospitals that are using the Balanced Scorecard and their
      implementation of metrics to influence performance and behavior. It is indeed
      possible for rural hospitals to meet and exceed the unique needs of patients and
      physicians (customers), to achieve healthy profit margins, and to be the rural
      hospital of choice that employees are proud to work for.

PMID- 17518022
TI  - Ira Moscovice on quality in rural healthcare settings. Interview by Sue Boisvert.

PMID- 17518023
TI  - A systems approach to improving core measure outcomes in a small rural facility.
AB  - In spring 2005, Fairview Hospital, a small rural critical access facility, began
      an initiative to develop an integrated system for performance measurement and
      improvement. The system involved an organization-level change in the process of
      data collection, analysis, and dissemination, coupled with an organization-level
      change in structure that used the performance data to bring about continuous
      improvement. The system entailed no new investment in technology. Within the
      integrated system framework, Fairview used a patient-level composite score
      methodology to achieve dramatic improvement in core measure outcomes. This
      article describes key elements of Fairview's integrated system, as well as the
      specific initiatives that led to performance improvement on core measures, with
      the primary purpose of providing a framework for organization-level improvement.

PMID- 17518024
TI  - Collaborative networks: helping rural laboratories achieve quality.
AB  - Rural hospital laboratories can combine some of their significant advantages with
      the benefits of an egalitarian, collaborative network to create a setting in
      which the disadvantages of their size (such as limited skill sets and resources)
      may be more readily overcome. Participation in a knowledge-sharing network, a
      coordinated effort at reference-range establishment and validation, and
      development of quality and safety algorithms help them avoid many potentially
      costly problems. This article describes the experience of developing such a
      network over a 30-year period and illustrates the benefits of this practice.

PMID- 17518025
TI  - Bringing performance improvement full circle.
AB  - Roane General Hospital (RGH), a critical access hospital, revised its performance
      improvement (PI) plan to ensure compliance and establish a system for promoting
      and sustaining performance. RGH used a modified approach to continuous quality
      improvement and developed a customized, circular process to guide PI. RGH strives
      to apply interventions based on data, monitor resulting effects, and start the
      process anew each year when indicators are evaluated and selected on the basis of
      need for improvement.

PMID- 17518026
TI  - On the little things.

PMID- 17518027
TI  - Improving the efficiency of hospital porter services, part 1: study objectives
      and results.
AB  - This article is the first of a 2-part series reporting the results of a 7-month
      study of porter operations at Vancouver General Hospital, Vancouver, British
      Columbia, Canada. Part 1 describes the importance of efficient porter services,
      the system's operation at the time of the study, the challenges faced in carrying
      out the study, the performance measures developed, the recommendations, and the
      outcomes. Part 2 describes the simulation model that measured the impact of
      system changes and the linear programming model developed to improve porter
      schedules.

PMID- 17518028
TI  - Improving the efficiency of hospital porter services, part 2: schedule
      optimization and simulation model.
AB  - This article is the second of a 2-part series on a study of porter operations at
      Vancouver General Hospital, Vancouver, British Columbia, Canada. Part 1 describes
      the importance of efficient porter services, the system's operation at the time
      of the study, the challenges faced in carrying out the study, the performance
      measures developed, the recommendations, and the outcomes. Part 2 describes the
      simulation model that measured the impact of system changes and the linear
      programming model developed to improve porter schedules.

PMID- 17518029
TI  - Managing the storm: an emergency department capacity strategy.
AB  - This article assesses the extent to which a team using quality improvement
      methods could improve the timeliness of the flow of admitted patients through the
      emergency department in one hospital. Using a structured approach, a
      multidisciplinary team redesigned the processes for admitting patients from the
      emergency department to the inpatient unit. Indicators of capacity limitations in
      the inpatient environment were also identified as triggers for a tiered
      institutional response to capacity constraints. Three time intervals in the
      admission process were identified for measuring performance, with comparisons to
      the same months of the previous year to determine significance. Significant
      reductions in the median minutes for a majority of the time intervals studied
      were achieved during the 6-month study period. The data from the study suggest
      that improvements in patient progression through an emergency department can be
      achieved with quality improvement methods. Success factors for this and other
      improvement strategies are discussed.

PMID- 17518030
TI  - Population control charts for population data.
AB  - Healthcare managers are beginning to collect full population data, rather than
      sample data, on some patient and performance measures. For example, hospitals and
      healthcare systems already gather and store comprehensive data on admissions,
      ambulatory encounters, and other procedures. And as the electronic medical record
      is more widely used, complete population data will be collected on an even wider
      range of clinical measures, such as blood pressure and Laboratory values, in both
      inpatient and outpatient settings. To correctly monitor process quality when
      working with full population data, rather than sample data, healthcare managers
      will need appropriate statistical tools. Traditional control charts, which are
      used for tracking processes over time, are not suitable for such population data
      because they are based on the assumption that sample data are being collected.
      The author proposes a new type of control chart specifically for use with such
      population data: population control charts. These control charts can be used for
      monitoring processes that have output measures with continuous, binomial, or
      nonbinomial rate variables.

PMID- 17518031
TI  - Thomas L. Garthwaite on healthcare quality in large enterprises. Interview by
      Danny van Leeuwen.

PMID- 17518032
TI  - What is quality? Do we agree, and does it matter?
AB  - The definition of quality is complex, elusive, and ambiguous. Cross-disciplinary
      definitions, usually assumed to be identical, vary in significant and subtle
      ways. Clear definition of a problem is the first step in correcting or improving
      it. Therefore, identification and increased understanding of disciplinary
      definitions of quality healthcare are needed. Development of a universal
      definition would be the ideal solution and would support quality improvement and
      patient safety efforts and programs. This article compares and contrasts
      definitions of quality in four selected healthcare disciplines and offers
      recommendations for how healthcare quality professionals might address and
      mitigate the ambiguity.

PMID- 17518033
TI  - Self-monitoring of a stress reduction technique using wrist-worn counters.
AB  - In a study of 59 veterans and healthcare workers, the reliability of a self
      monitoring method used to track the frequency of a spiritually oriented stress
      reduction technique was assessed. During a 5-week program of silently repeating a
      mantram (a spiritual word or phrase) to lower stress and anger and improve
      spiritual well-being, portable wrist-worn counters were used to track daily
      mantram practice sessions. All outcomes significantly improved in the
      hypothesized direction. Mantram practice tracked by the counters was highly
      correlated (r = .84) with retrospective self-reports, indicating that such
      counters may be a reliable self-monitoring tool and could be used to measure a
      variety of other behavioral health quality indicators.

PMID- 17518034
TI  - Exploring moral distress in the long-term care setting.
AB  - Moral distress has the potential to affect every practice setting in nursing;
      however little research has been conducted that examines the presence and impact
      of moral distress for nurses working in long-term care. This article reports the
      results of a pilot study that examined the experience and presence of moral
      distress of registered nurses in a long-term care setting. A convenience pilot
      sample of 6 nurses participated in audio-taped open-ended interviews. Interview
      questions were formulated using Corley's theory of moral distress as the
      theoretical framework. Findings indicated that nurses' experiences of moral
      distress were precipitated most often by disagreements with family regarding
      treatment decisions for residents that impacted quality of life and lack of
      resources to meet residents' assessed needs. Moral distress had both a positive
      and negative impact on nurses with nurses reporting that the presence of moral
      distress had little impact on the quality of care received by residents.

PMID- 17518035
TI  - Clean those teeth.

PMID- 17518036
TI  - Recent progress in the improvement of the coupling efficiency of "difficult
      sequences" in peptide synthesis.
AB  - Even though chemistry is now in place that potentially allows high coupling
      efficiencies to be attained, successful coupling is usually a challenge when so
      called "difficult sequences" is encountered in peptide synthesis. Some factors
      that affect the coupling efficiency have been discussed and related methods to
      overcome those obstacles have been introduced in present review. All suggestions
      proposed here are valuable and also feasible to improve the coupling completeness
      in both liquid-phase or solid-phase

PMID- 17518037
TI  - [Recent advances in the study of natural homoisoflavonoids].
AB  - Homoisoflavonoid is a special type in flavonoids. There are more than 110
      homoisoflavonoid compounds isolated from natural materials. Homoisoflavonoid
      compounds show many bioactivities on anti-inflammatory, estrogenicy,
      antiestrogenic, anticancer and angioprotective etc. This paper summarized the
      plant sources, structural types spectrocopy features and the biology activities
      of homoisoflavonoids.

PMID- 17518038
TI  - [Recent advances in the applications of ultrasonic microbubbles as gene delivery
      systems].
AB  - Ultrasonic beam can be focused on a particular tissue. As ultrasound contrast
      agents for medical ultrasound imaging, gas-filled microbubbles can also be used
      as drugs or gene carriers. Therefore, ultrasonic microbubbles become a topic of
      intense interest in drug delivery because they can be used as gene targeting
      delivery systems. Based on the relevant materials, the applications of ultrasonic
      microbubbles as gene delivery systems in various tissues in vivo were reviewed,
      such as cardiac, vascular, skeletal muscle and tumor. Their potential problems in
      future use were also discussed.

PMID- 17518039
TI  - [Effect of lidamycin on mitochondria initiated apoptotic pathway in human cancer
      cells].
AB  - Although enediyne antibiotic lidamycin ( LDM) is a potent inducer of apoptosis,
      the underlying mechanisms of its apoptotic functions remain to be explored. Here,
      we aim to elucidate its possible mechanisms in mitochondria initiated apoptotic
      pathway involved in human BEL-7402 and MCF-7 cells. Cytochrome c released from
      mitchondria to cytosol fraction was detected by Western blotting. p53 and Bax,
      Bcl-2 expressions were detected by Western blotting and RT-PCR. MTT assay was
      used to detect cytotoxicity of LDM with or without caspase inhibitor z-VAD-fmk.
      After the BEL-7402 cells were exposed to 0. 1 micromol x L(-1) LDM within 6 h,
      the increase of cytochrome c in the cytosol and decrease in the mitochondria were
      observed when compared with untreated cells. The expression of Bax, an important
      proapoptotic member of the Bcl-2 family, increased gradually in the BEL-7402
      cells after exposure to LDM of 0. 1 micromol x L (-1) for 2, 6, and 9 h,
      separately, while Bcl-2 increased at 2 and 6 h, and decreased at 9 h after LDM
      treatment. Enhanced protein expressions were parallel with respective increased
      mRNA level for Bax only, but not p53. Caspase inhibitor may inhibit partially the
      killing effects induced by LDM. Therefore we conclude that the rapid activation
      of mitochondrial pathway induced by LDM in tumor cells might contribute to its
      highly potent cytotoxicities.

PMID- 17518040
TI  - [Effects of matrine, oxymatrine and resveratrol on HERG channel expression].
AB  - Because HERG potassium channel has important effects on both proarrhythmia and
      antiarrhythmia, we use immunofluorescence and Western blotting methods to detect
      the expression of HERG channel of HERG-HEK cells in different concentrations of
      matrine, oxymatrine and resveratrol. The findings showed that both matrine (1
      micromol x L(-1) ) and oxymatrine ( 1micromol x L (-1) ) increased HERG channel
      expression ( n = 5, P < 0. 05 ) , while matrine (100 micromol x L(-1) ) decreased
      HERG channel expression ( n = 5, P < 0. 05), resveratrol didn't affect HERG
      channel expression. In conclusion, different concentrations of matrine and
      oxymatrine affect HERG channel expression, while there is no relationship between
      resveratrol and HERG channel expression. It provides a theoretical support for
      the safety and mechanism of anti-arrhythmic drugs.

PMID- 17518041
TI  - [Effects of doxazosin enantiomers on alpha-adrenoceptors of isolated rabbit blood
      vessels].
AB  - Doxazosin, a high selective alpha1-adrenoceptor antagonist, is considered as the
      first-line therapy for the patients with benign prostatic hyperplasia (BPH) and
      also produce several side effects in cardiovascular system. In this study, we
      observed the isometric vasoconstrictive responses of the rabbit isolated arterial
      rings to electric field stimulation and noradrenaline ( NA ) to study the effects
      of R-doxazosin ( R-DOX ) and S-doxazosin ( S-DOX ) on the alpha1-adrenoceptor
      regulated vasoconstrictive responses in the rabbit isolated ear artery,
      mesenteric artery and pulmonary artery, and the effects of higher concentration
      of S-DOX and R-DOX on presynaptic alpha2-adrenoceptor-regulated purinergic
      vasoconstriction in the rabbit isolated saphenous artery. We found that R-DOX and
      S-DOX competitively inhibited the vasoconstriction induced by NA in the rabbit
      isolated ear artery, mesenteric artery and pulmonary artery. The pA2 values of R
      DOX and S-DOX against NA in the rabbit isolated ear artery, mesenteric artery and
      pulmonary artery were 7. 91 +/- 0. 03 and 7. 53 +/- 0. 05, 7. 80 +/- 0. 05 and 7.
      29 +/-0. 07, 8. 32 +/- 0. 06 and 7. 97 +/- 0. 07, respectively. The pA2 values of
      R-DOX in the three arterial preparations were significantly higher than those of
      S-DOX (P < 0. 01). R-DOX and S-DOX at the concentrations of 0. 1 - 10 micromol x
      L (-1) did not affect the vasoconstriction induced by electric stimulation in the
      rabbit isolated saphenous artery. R-DOX and S-DOX at 100 micromol x L(-1) in the
      rabbit isolated saphenous artery completely inhibited the vascular responses to
      exogenous NA, but did not affect the vascular responses to exogenous adenosine
      triphosphate (1 mmol x L(-1) ). It is reasonable to suggest that R-DOX and S-DOX
      competitively inhibit the vasoconstriction induced by NA in the rabbit ear
      artery, mesenteric artery and pulmonary artery, and the pA2 values of S-DOX are
      significantly lower than those of R-DOX. The higher concentration (10 micromol x
      L(-1)) of R-DOX and S-DOX does not affect the presynaptic alpha2-adrenoceptors at
      sympathetic nerve terminals of the rabbit saphenous artery.

PMID- 17518042
TI  - [Synthesis and bioactivity of N- [4- ( benzimidazole-2-thio) phenyl] -N'-alkyl
      guanidine derivatives].
AB  - In order to get some novel compounds with potent iNOS inhibitory activity, 12
      target compounds of N-[ 4-( benzimidazole-2-thio) phenyl ] -N'-alkyl guanidine
      derivatives ( I1- I12 ) were synthesized from 1-benzoyl-3-[ 4-( benzimidazole-2
      thio) phenyl] thioureas (4) by hydrolysis with 2. 0 mol x L(-1) sodium hydroxide
      solution containing tetrahydrofuran to form the corresponding N-[ 4
      (benzimidazole-2-thio) phenyl] thioureas (5) which was S-ethylated with ethyl
      iodide, followed by amination with primary amines or secondary amines. The
      intermediate 4 was synthesized from 2-mercaptobenzimidazole (1) by reaction with
      1-chloro-4-nitrobenzene to form 2-( 4-nitrophenylthio) benzimidazole (2) which
      was reduced by iron powder and hydrochloric acid, followed by reaction with
      benzoyl isothiocyanate. The structures of compounds I1 - I12 were confirmed by
      IR, MS,1H NMR and elemental analysis. The results of preliminary pharmacological
      test showed that the activities of three compounds (I 1, I8 and I10) were
      stronger than aminoguanidine, especially for compound I1.

PMID- 17518043
TI  - [Evolutionary trace analysis of N-myristoyltransferase family].
AB  - To clarify the important functional residues in the active site of N
      myristoyltransferase (NMT), a novel antifungal drug target, and to guide the
      design of specific inhibitors, multiple sequence alignments were performed on the
      NMT family and thus evolutionary trace was constructed. The important functional
      residues in myristoyl CoA binding site, catalytic center and inhibitor binding
      site of NMT family were identified by ET analysis. The trace residues were mapped
      onto the active site of CaNMT. Trpl26, Asn175 and Thr211 are highly conserved
      trace residues and do not interact with current NMT inhibitors, which are
      potential novel drug binding sites for the novel inhibitor design. Pro338,
      Leu350, Ile352 and Ala353 are class-specific trace residues, which are important
      for the optimization of current NMT inhibitors. The trace residues identified by
      ET analysis are of great importance to study the structure-function relationship
      and also to guide the design of specific inhibitors.

PMID- 17518044
TI  - Diterpenes from Helianthus annuus and their cytotoxicity in vitro.
AB  - To search for bioactive compounds from the flower disc of Helianthus annuus L.,
      chromatography was used to isolate and purify the chemical constituents, their
      structures were identified by spectral analysis, MTT method was applied to
      investigate their cytotoxic activities, some compounds showed moderate cytotoxic
      activities on SF-268, MCF-7 and HepG2 cell lines. Eleven compounds were obtained
      from the flower disc of H. annuus, and identified as ent-kaurane-2alpha, 16alpha
      diol (1) and entkaurane-15alpha,16alpha-epoxy-17-al-19-oic acid (2), and nine
      known diterpenes, ent-kaurane-16P-ol (3), phyllocladan-16beta-ol (4) , ent-atisan
      16a-ol (5) , grandifloric acid (6) , angeloylgrandifloric acid (7), ent-kaurane
      16-en-19-oic acid (8), ent-kaurane-17-hydroxy-15-en-19-oic acid (9), ent-kaurane
      16beta, 17-dihydroxy-19-oic acid (10), and ciliaric acid (11). Compounds 1 and 2
      are new compounds, some compounds showed cytotoxic activities on SF-268, MCF-7
      and HepG2 cell lines.

PMID- 17518045
TI  - [A new saponin from Koelreuteria paniculata].
AB  - AIM: To investigate the chemical constituents of seeds of Koelreuteria paniculata
      Laxm. , components were separated by means of solvent extraction and
      chromatography on C18, the structure of compound was determined by spectral
      analysis and chemical evidences. One saponin was obtained and identified as 28-O
      isopentyryl-3beta, 16alpha, 22beta, 28-tetrahydroxyl-oleanane-3-O-[ alpha-L
      rhamnopyranosyl- ( 1-->3) -betaD-galactopyranosyl-( 1--->4' )]-3betaD
      galacturonopyranoside, named paniculata saponin C. This saponin is a new
      compound.

PMID- 17518046
TI  - [Isolation and identification of phenolic constituents from Juncus effusus].
AB  - To study the phenolic constituents from the dry stem of Juncus effusus L. , the
      constituents were isolated by normal-phase and reverse-phase silica gel column
      chromatography from the EtOAc extract. Their structures were elucidated by
      spectral analysis. Six phenolic constituents were purified and identified as 7
      carboxy-2-hydroxy-1-methyl-5-vinyl-9,10-dihydrophenanthrene (1) , 2,3-isopylidene
      1-O-ferulic acid glyceride ( 2 ) , ( 2S )-2, 3-isopylidene-1-0-p-coumaroyl
      glyceride (3 ) , dehydroeffusal ( 4 ) , p-hydroxybenzaldehyde (5) and luteolin
      5,3'-dimethyl ether (6). Compounds 1 and 2 are new compounds. Compounds 5 and 6
      were isolated from Juncaceae plant for the first time. 13C NMR data of compound 6
      were reported for the first time.

PMID- 17518047
TI  - [Anti-HIV chemical constituents of aerial parts of Caragana rosea].
AB  - This study was intended to look for anti-HIV chemical constituents of aerial
      parts of Caragana rosea Turcz. Column chromatographic technique was used for the
      isolation and purification of constituents of Caragana rosea under the guide of
      anti-HIV assay. The structures were established on the basis of physical and
      chemical properties and spectroscopic data. Five compounds were obtained from the
      EtOAc fraction of aerial parts of Caragana rosea and identified as myricetin (1),
      mearnsetin (2), p-hydroxy cinnamic acid (3), cararosinol A (4) and cararosinol B
      (5). At the same time, one possible transformation route between cararosinol B
      and kobophenol A, another resveratrol tetramer isolated from this plant
      previously, was proposed. Compounds 4, 5 are new resveratrol tetramers, compounds
      1 -3 were isolated from this plant for the first time. All compounds showed no
      activities in an in vitro assay against HIV-1.

PMID- 17518048
TI  - [Three new flavonoid glycosides from Peperomia dindygulensis].
AB  - To study the chemical constituents of Peperomia dindygulensis Miq. ,
      chromatography was used to isolate and purify the chemical constituents, their
      structures were elucidated by spectroscopic data and physical-chemical
      properties. Three compounds were obtained. They were identified as: hypolacetin
      4',7-dimethyl ether-8-O-beta-D-glucopyranoside (I) , isoscutellarein-4'-methyl
      ether-8-O-alpha-L-arabinopyrano-syl-(1--> 4)-beta-D-glucopyranoside ( II) ,
      isoscutellarein-4', 7-dimethyl ether-8-O-alpha-L-arabinopyranosyl-(1-->4) -betea
      D-glucopyranoside (III). Compounds I, II and III are all new compounds.

PMID- 17518049
TI  - [Analysis of essential oil in herba ephedrae-ramulus cinnamomi by GC-MS and
      chemometric resolution method].
AB  - Gas chromatography/mass spectrometry, chemometric resolution method ( CRM) and
      overall volume integration method were used to analyze the essential components
      of herbal pair Herba Ephedrae-Ramulus Cinnamomi (HP HE-RC) and compare it with
      that of single herbs HE and RC. 72, 68, and 97 essential components in essential
      oil of HE, RC, and HP HE-RC were determined, accounting for 90. 08% , 91. 62% ,
      and 89. 76% of total contents of essential oil of HE, RC, and HP HE-RC,
      respectively. The numbers of essential components of HP HE-RC are almost the
      summation of that of two single herbs, but some relative contents of them are
      changed. Some new components, such as 1, 6-dimethylhepta-1,3,5-triene,
      tetracyclo[4. 2. 1.1 (2,5 ). 0 (9,10) ] deca-3,7-diene, globulol, ( E, E) -6,
      10,14-trimethyl-5,9,13-pentadecatrien-2 -one, etc. have been found in HP HE-RC
      because of chemical reactions and physical changes during the course of
      decocation.

PMID- 17518050
TI  - [Relative adscriptions of components in the effective fractions of Yinqiao
      decoction and its composing individual herbs].
AB  - HPLC and LC-MS/MS were used to establish a comprehensive HPLC analytical method
      of Yinqiao decoction and identify the chemical constituents of the whole and
      individual herbs of Yinqiao decoction. YWG-C18 (250 mm x4. 6 mm ID, 10 microm)
      column was used; the mobile phase was composed of acetonitrile (A) and water ( B,
      with 3% acetic acid) with gradient elution; the flow rate was 1. 0 mL x min(-1)
      and the column temperature was set up at 25 degrees C. The detection wavelength
      was 280 nm. The chromatographic fingerprints of Yinqiao Decoction showed 30 main
      peaks. Peak 2, 14, 15, 17 were from Lonicera japonica Thunb, peak 3, 12, 13, 24
      were from Fosythia suspense (Thunb) Vahl, peak 19, 25, 26, 27 were from Arctium
      lappa L. , peak 5, 6, 8, 9, 10, 11, 18, 28 were from Glycyrrhiza uralensis Fisch,
      peak 20, 21 were from Mentha haplocalyx Briq. , peak 22, 23 were from
      Schizonepeta tenuifolia Briq. , peak 1 presented in the chromatograms of Lonicera
      japonica Thunb, Fosythia suspense (Thunb) Vahl, Mentha haplocalyx Briq. ,
      Schizonepeta tenuifolia Briq. and Platycodon grandiflorum (Jacq. ) A. DC. , peak
      7 presented in the chromatograms of Fosythia suspense (Thunb) Vahl and Glycine
      max (L. ) Merr. , peak 16 presented in the chromatograms of Mentha haplocalyx
      Briq. and Schizonepeta tenuifolia Briq. , peak 29 presented in the chromatograms
      of the herbs except Mentha haplocalyx Briq. and Platycodon grandiflorum (Jacq. )
      A. DC. , peak 30 presented in the chromatograms of the herbs except Platycodon
      grandiflorum (Jacq. ) A. DC. , peak 4 was not identified, maybe it was a new
      constituent produced during decoction. By comparison of the standards isolated
      and MS spectra, 14 peaks were identified as 2 ( chlorogenic acid) , 9 (
      liquiritin ) , 10 ( 4'-O-[ beta-D-apiofuranosyl (1--> 2 ) -beta-D-glucopyranosyl]
      liquiritigenin), 12 (forsythiaside), 13 (rutin), 14 (4,5-O-dicaffeoylquiniic
      acid), 15 (3, 5-O-dicaffeoylquiniic acid ), 16 ( 4-0- [ beta-D-apiofuranosyl ( 1 
      ->2 ) -beta-D-glucopyranosyl ] isoliquiritigenin) , 17 ( 3, 4-O-dicaffeoylquiniic
      acid) , 18 (2'-O-[ beta-D-apiofuranosyl (1 -->2 ) -beta-D-glucopyranosyl]
      isoliquiritigenin) , 19 (arctiin) , 20 (linarin) , 25 (genistein) , 28 (
      isoliquiritigenin) . The method could be used to identify the characteristics of
      Yinqiao decoction, and it could be used to evaluate the quality and quantity of
      Yinqiao decoction.

PMID- 17518051
TI  - [Pharmacokinetics of PEG-rhG-CSF and rHSA-hG-CSF in mice determined with ELISA].
AB  - Double antibody sandwich-type ELISA was used to detect rhG-CSF in serum to study
      the pharmacokinetics of rhG-CSF, PEG-rhG-CSF and rHSA-hG-CSF in mice and to
      confirm that PEGlyation and albumin fusion of rhG-CSF technology can prolong half
      life of G-CSF. Pharmacokinetic parameters were calculated with 3P87 software.
      T1/2 s of rhG-CSF, PEG-rhG-CSF and rHSA-hG-CSF are 2. 1 , 14.2 and 10. 6 h,
      respectively. T1/2 s of PEG- rhG-CSF and rHSA-hG-CSF are 7, 5 times than T1/2 s
      of rhG-CSF, respectively. Tpeak s of PEG-rhG-CSF and rHSA-hG-CSF are 15, 13 times
      than Tpeak of rhG-CSF, respectively. The result of ELISA indicates that
      PEGlyation and albumin fusion of rhG-CSF technology can prolong half-life of G
      CSF.

PMID- 17518052
TI  - [Analysis of aconite alkaloids in the combination of radix aconiti lateralis
      preparata with different herbs by ESI-MS spectrometry].
AB  - The method was established study the influence of different herbal combination
      with Radix Aconiti in the traditional medical formulae on content of the aconite
      alkaloids, for elucidating the scientific basis of reducing the toxicity of
      aconite in traditional Chinese medical formulation. The samples for ESI-MS study
      were prepared by decocting a mixture of Radix Aconiti Lateralis Preparata ( RALP)
      with Radix Glycyrrhizae Preparata (RGP) , Radix Paeoniae Alba ( RPA) , Rhizoma
      Zingiberis (RZ) or Radix Et Rhizoma Rhei ( RERR) , separately, and extracting the
      residue of the above mentioned mixtures after decocting. The diester-diterpenoid
      alkaloids (DDAs) was lower in the herb couples of RALP-RGP, RALP-RPA, RALP-RZ and
      RALP-RERR, and lipo-alkaloids was increased in the herb couples of RALP-RGP, RALP
      RPA and RALP-RZ. The reason of reducing toxic effect principle is that the
      components of RGP, RPA and RZ have ester-exchange reactions with DDAs in RALP to
      produce lipo-alkaloids of low toxicity in the decocting process of the herb
      couples. The combination of RALP-RERR can reduce the content of DDAs in decoction
      and residue due to the formation of water insoluble alkaloid compound.

PMID- 17518053
TI  - [Preparation of budesonide-poly (ethylene oxide) solid dispersions using
      supercritical carbon dioxide and in vitro evaluation].
AB  - An application of supercritical fluids technology for processing of budesonide
      poly (ethylene oxide) solid dispersions was presented. The correlations of the
      operation parameters in the preparation process were studied. Solid dispersions
      of budesonide in poly (ethylene oxide) were prepared using a static method for
      supercritical carbon dioxide and characterized by powder X-ray diffractometry,
      differential scanning calorimetry, intrinsic dissolution, and in vitro
      dissolution. It was found that the optimum condition of solid dispersions
      formation was as follows: temperature, 40 degrees C ; pressure, 20 MPa; the ratio
      of budesonide and poly (ethylene oxide) , 1: 10. Drug existed in amorphous state
      in hydrophilic poly (ethylene oxide) carriers and intrinsic solubility and
      dissolution rates were significantly enhanced. The mechanism of the enhanced
      dissolution may be attributed to the amorphous character of the budesonide,
      improvement of the wettability of the hydrophobic budesonide, together with the
      formation of hydrogen bond of budesonide and hydrophilic poly (ethylene oxide).
      The supercritical fluids process can be used as an alternative method for
      preparation of solid dispersions.

PMID- 17518054
TI  - [Preparation and properties of Talpha1 loaded injectable sustained release
      microspheres].
AB  - To prepare thymosin alpha-1 (Talpha) loaded injectable sustained release
      microspheres and to evaluate its release behavior, bioactivities in vitro as well
      as its pharmacodynamics in vivo, Talpha1 loaded microspheres was prepared with
      poly ( lactic-co-glycolic acid) (PLGA) as carrier material by double emulsion
      (W/O/W) method. Physical and chemical properties of microspheres, such as mean
      diameter, The release behavior and its influencing factors were morphology and
      drug loading were evaluated. evaluated by HPLC determination. The bioactivity of
      Talpha1 in the course of encapsulation process and in vitro release ware
      evaluated by CCK-8 method. The ratio of CD4+/CD8+ in blood was determined with
      flow cytometry and the pharmacodynamics of Ta, loaded microspheres was evaluated
      by the change of CD4+/ CD8+. Microspheres with good shape and dispersive quality
      were prepared. The drug entrapment efficiency of two optimizing prescriptions
      containing 5% NaCl and 10% glucose as outer water phase were 87. 8% and 90. 2% ,
      respectively. The cumulated release in one month is up to 90%. The bioactivity of
      Talpha was conserved with glucose as outer water phase, but in the course of in
      vitro release, the specific activity of Talpha in the microspheres decreased a
      little. Talpha microspheres can increase significantly the immunity of immuno
      suppressed rats. Talpha can be encapsulated in injectable microspheres to yield
      one-month continuous release when using biodegradable polymers PLGA as carrier
      material, and this technique will have a favorable perspective in the near
      future.

PMID- 17518055
TI  - [Preparation and gene expression of transferrin modified gene loaded procationic
      liposomes].
AB  - A novel transferrin modified non-viral gene delivery system Tf-PLPD was developed
      and the related characteristics was investigated. Blank procationic liposomes
      were prepared by film dispersion-filteration method. PLPD was prepared as follows
      by first mixing the plasmid DNA and protamine together, then the resulted
      polyplexes were incubated for 10 min at room temperature, followed by addition of
      preformed blank procationic liposomes. Transferrin was adsorbed at the surface of
      PLPD via electrostatic interactions to form Tf-PLPD. Central composite design
      (CCD) was employed to optimize the formulation. The HepG2 cells were transfected
      using lacZ as reporter gene and characteristics such as the morphology, the mean
      particle size, the zeta potential and the transfection efficiency in HepG2 cells
      were further investigated by different methods. The resulting PLPD had a regular
      spherical surface with an average size of (228. 9 +/- 8. 0) nm (polydispersity
      index, PDI = 0. 122 +/- 0. 02, n = 3) , a zeta potential of ( - 25. 08 +/-2. 50)
      mV (n = 3) and a transfection efficiency of (12. 18 +/- 3. 80) mU x mg(-1)
      (protein). The Tf-PLPD had an average size of (240 +/- 12) nm (polydispersity
      index, PDI = 0. 150 +/- 0. 03, n = 3), a zeta potential of ( - 24. 10 +/- 2. 50)
      mV ( n = 3) and a transfection efficiency of (24. 26 +/- 2. 60) mU x mg(-1)
      (protein) , 20 times greater than that of the naked plasmid DNA. The presence of
      serum didn' t affect the tansfection activity of PLPD or Tf-PLPD. Compared to one
      kind of cationic liposomes (liposome-protamine-DNA, LPD), the PLPD and Tf-PLPD
      had much less cytotoxicity to three hepatic cell lines (including HepG2, SMMC7721
      and Chang' s normal hepatocyte). The results indicated that the Tf-PLPD is a
      perspective non-viral vector for gene delivery systems.

PMID- 17518056
TI  - [Metabolism of mitomycin C by human liver microsomes in vitro].
AB  - To provide the profiles of metabolism of mitomycin C (MMC) by human liver
      microsomes in vitro, MMC was incubated with human liver microsomes, then the
      supernatant component was isolated and detected by HPLC. Types of metabolic
      enzymes were estimated by the effect of NADPH or dicumarol (DIC) on metabolism of
      MMC. Standard, reaction, background control (microsomes was inactivated),
      negative control (no NADPH), and inhibitor group (adding DIC) were assigned, the
      results were analyzed by Graphpad Prism 4. 0 software. Reaction group compared
      with background control and negative control groups, 3 NADPH-dependent absorption
      peaks were additionally isolated by HPLC after MMC were incubated with human
      liver microsomes. Their retention times were 10. 0, 14. 0, 14. 8 min ( named as
      Ml, M2, M3) , respectively. Their formation was kept as Sigmoidal dose-response
      and their Km were 0. 52 (95% CI, 0. 40 - 0.67) mmol x L(-1), 0. 81 (95% CI, 0. 59
      - 1. 10) mmol x L(-1), 0. 54 (95% CI, 0. 41 -0. 71) mmol x L(-1) , respectively.
      The data indicated that the three absorption peaks isolated by HPLC were
      metabolites of MMC. DIC can inhibit formation of M2, it' s dose-effect fitted to
      Sigmoidal curve and it' s IC50 was 59. 68 (95% CI, 40. 66 - 87. 61) micromol x L(
      1) , which indicated DT-diaphorase could take part in the formation of M2. MMC
      can be metabolized by human liver microsomes in vitro, and at least three
      metabolites of MMC could be isolated by HPLC in the experiment, further study
      showed DT-diaphorase participated in the formation of M2.

PMID- 17518057
TI  - [The delivery mechanism of micro-porous osmotic pump tablets].
AB  - To investigate the delivery mechanism of micro-porous osmotic pump tablets (
      MPOP), taking tramadol hydrochloride ( TR) as the model drug, tramadol
      hydrochloride micro-porous osmotic pump tablets (TR MPOP) were prepared with
      compressible starch as diluent, cellulose acetate as coating material,
      polyethylene glycol 400 as pore-forming agents. The equilibrium solubility and
      osmolality of TR were determined. The effects of fillers in tablet cores, coating
      levels, and osmotic pressures of release media on expansion behavior of
      preparations were described. The influences of the category, osmolality, and pH
      value of release media, release methods, and release conditions on release curves
      of tablets were evaluated. Based on several models, the delivery pattern of TR
      MPOP was fitted. The equilibrium solubility in water and osmolality of TR were
      (775.8 +/- 17.7) g x L(-1) and 4.036 Osmol x kg(-1), respectively. During the
      drug-release period, it was observed that the tablets expanded markedly in
      response to the expansion characteristics of compressible starch and the osmotic
      pressure difference across the membrane. When osmotic pressure of release media
      increased, the significant change of the equilibrium solubility of TR was not
      found, but the release rates of TR MPOP decreased significantly. The delivery
      rate was not influenced by the pH of release mediums, dissolution methods and
      paddle stirring rates. The drug release profile conformed to the model of zero
      order in 8 h. The pore-forming agents were dissolved in release medium, which
      caused micro-pores. The expansion of tablets made the size of micropores bigger,
      and then the drug-releasing pores were obtained. It was proved that the drivers
      of drug delivering from TR MPOP were mainly the difference of osmotic pressure,
      and secondly the difference of solubility. TR MPOP were the controlled-release
      preparation.

PMID- 17518058
TI  - Electrical impedance tomography for piecewise constant domains using boundary
      element shape-based inverse solutions.
AB  - Shape-based solutions have recently received attention for certain ill-posed
      inverse problems. Their advantages include implicit imposition of relevant
      constraints and reduction in the number of unknowns, especially important for
      nonlinear ill-posed problems. We apply the shape-based approach to current
      injection electrical impedance tomography (EIT) reconstructions. We employ a
      boundary element method (BEM) based solution for EIT. We introduce two shape
      models, one based on modified B-splines, and the other based on spherical
      harmonics, for BEM modeling of shapes. These methods allow us to parameterize the
      geometry of conductivity inhomogeneities in the interior of the volume. We assume
      the general shape of piecewise constant inhomogeneities is known but their
      conductivities and their exact location and shape is not. We also assume the
      internal conductivity profile is piecewise constant, meaning that each region has
      a constant conductivity. We propose and test three different regularization
      techniques to be used with either of the shape models. The performance of our
      methods is illustrated via both simulations in a digital torso model and phantom
      experiments when there is a single internal object. We observe that in the noisy
      environment, either simulated noise or real sources of noise in the experimental
      study, we get reasonable reconstructions. Since the signal-to-noise ratio (SNR)
      expected in modern EIT instruments is higher than that used in this study, these
      reconstruction methods may prove useful in practice.

PMID- 17518059
TI  - A pattern-theoretic characterization of biological growth.
AB  - Mathematical and statistical modeling of biological growth is an important
      problem in medical diagnostics. Here, we seek tools to analyze changes in
      anatomical parts using images collected over time. We introduce a structured
      model, called Growth by Random Iterated Diffeomorphisms (GRID), that treats a
      cumulative growth deformation as a composition of several elementary
      deformations. Each elementary deformation applies to a small region by capturing
      deformation local to that region and is characterized by a seed and a radial
      deformation pattern around that seed. These GRID variables--seed locations and
      radial deformation patterns---are estimated from observed images in two steps: 1)
      estimate a cumulative deformation over an observation interval; 2) estimate GRID
      variables using maximum-likelihood criterion from this estimated cumulative
      deformation. We demonstrate this framework using an MRI image data of a rat's
      brain growth. For future statistical analysis, we propose a time-varying Poisson
      process for the seed placements and a random drawing from a predetermined catalog
      of deformations for the radial deformation patterns.

PMID- 17518060
TI  - Imaging the distribution of magnetic nanoparticles with ultrasound.
AB  - Magnetic nanoparticles can be caused to oscillate under the influence of an
      incident ultrasonic wave. If the particles are momentarily aligned with a
      magnetizing pulse creating a macroscopic magnetization, this oscillation will
      result in a time-varying magnetic moment which should be detectable as an induced
      voltage in a nearby pickup coil. In this way, focused ultrasound can be used to
      map, or image, the spatial distribution of the magnetic particles after these
      particles have been introduced into the body. The magnetic particles could be
      antibody-labeled to target tumor cells or used as a cardiovascular contrast
      agent, among other applications. The magnitude of the induced signal is estimated
      for one micron particles with a Fe/tissue volume fraction of 10(-6), which is
      about the limit of detectability for MRI superparamagnetic contrast agents
      consisting of single domain iron-oxide particles. One advantage of this method
      compared to conventional MRI is potentially greater sensitivity due to the
      absence of a large background signal.

PMID- 17518061
TI  - Learning active shape models for bifurcating contours.
AB  - Statistical shape models are often learned from examples based on landmark
      correspondences between annotated examples. A method is proposed for learning
      such models from contours with inconsistent bifurcations and loops. Automatic
      segmentation of tibial and femoral contours in knee X-ray images is investigated
      as a step towards reliable, quantitative radiographic analysis of osteoarthritis
      for diagnosis and assessment of progression. Results are presented using various
      features, the Mahalanobis distance, distance weighted K-nearest neighbours, and
      two relevance vector machine-based methods as quality of fit measure.

PMID- 17518062
TI  - Texture anisotropy of the brain's white matter as revealed by anatomical MRI.
AB  - The purpose of this work was to study specific texture properties of the brain's
      white matter (WM) based on conventional high-resolution T1-weighted magnetic
      resonance imaging (MRI) datasets. Quantitative parameters anisotropy and
      laminarity were derived from 3-D texture analysis. Differences in WM texture
      associated with gender were evaluated on an age-matched sample of 210 young
      healthy subjects (mean age 24.8, SD 3.97 years, 103 males and 107 females).
      Changes of WM texture with age were studied using 112 MRI-T1 datasets of healthy
      subjects aged 16 to 70 years (57 males and 55 females). Both texture measures
      indicated a "more regular" WM structure in females (p < 10(-6)). An age-related
      deterioration of WM structure manifests itself as a remarkable decline of both
      parameters (p < 10(-6)) that is more prominent in females (p < 10(-6)) than in
      males (p = 0.02). Texture analysis of anatomical MRI-T1 brain datasets provides
      quantitative information about macroscopic WM characteristics and helps
      discriminating between normal and pathological aging.

PMID- 17518063
TI  - Improved reconstruction for MR spectroscopic imaging.
AB  - Sensitivity limitations of in vivo magnetic resonance spectroscopic imaging
      (MRSI) require that the extent of spatial-frequency (k-space) sampling be
      limited, thereby reducing spatial resolution and increasing the effects of Gibbs
      ringing that is associated with the use of Fourier transform reconstruction.
      Additional problems occur in the spectral dimension, where quantitation of
      individual spectral components is made more difficult by the typically low signal
      to-noise ratios, variable lineshapes, and baseline distortions, particularly in
      areas of significant magnetic field inhomogeneity. Given the potential of in vivo
      MRSI measurements for a number of clinical and biomedical research applications,
      there is considerable interest in improving the quality of the metabolite image
      reconstructions. In this report, a reconstruction method is described that makes
      use of parametric modeling and MRI-derived tissue distribution functions to
      enhance the MRSI spatial reconstruction. Additional preprocessing steps are also
      proposed to avoid difficulties associated with image regions containing spectra
      of inadequate quality, which are commonly present in the in vivo MRSI data.

PMID- 17518065
TI  - Rayleigh-maximum-likelihood filtering for speckle reduction of ultrasound images.
AB  - Speckle is a multiplicative noise that degrades ultrasound images. Recent
      advancements in ultrasound instrumentation and portable ultrasound devices
      necessitate the need for more robust despeckling techniques, for both routine
      clinical practice and teleconsultation. Methods previously proposed for speckle
      reduction suffer from two major limitations: 1) noise attenuation is not
      sufficient, especially in the smooth and background areas; 2) existing methods do
      not sufficiently preserve or enhance edges--they only inhibit smoothing near
      edges. In this paper, we propose a novel technique that is capable of reducing
      the speckle more effectively than previous methods and jointly enhancing the edge
      information, rather than just inhibiting smoothing. The proposed method utilizes
      the Rayleigh distribution to model the speckle and adopts the robust maximum
      likelihood estimation approach. The resulting estimator is statistically analyzed
      through first and second moment derivations. A tuning parameter that naturally
      evolves in the estimation equation is analyzed, and an adaptive method utilizing
      the instantaneous coefficient of variation is proposed to adjust this parameter.
      To further tailor performance, a weighted version of the proposed estimator is
      introduced to exploit varying statistics of input samples. Finally, the proposed
      method is evaluated and compared to well-accepted methods through simulations
      utilizing synthetic and real ultrasound data.

PMID- 17518064
TI  - Genetic algorithms for finite mixture model based voxel classification in
      neuroimaging.
AB  - Finite mixture models (FMMs) are an indispensable tool for unsupervised
      classification in brain imaging. Fitting an FMM to the data leads to a complex
      optimization problem. This optimization problem is difficult to solve by standard
      local optimization methods, such as the expectation-maximization (EM) algorithm,
      if a principled initialization is not available. In this paper, we propose a new
      global optimization algorithm for the FMM parameter estimation problem, which is
      based on real coded genetic algorithms. Our specific contributions are two-fold:
      1) we propose to use blended crossover in order to reduce the premature
      convergence problem to its minimum and 2) we introduce a completely new
      permutation operator specifically meant for the FMM parameter estimation. In
      addition to improving the optimization results, the permutation operator allows
      for imposing biologically meaningful constraints to the FMM parameter values. We
      also introduce a hybrid of the genetic algorithm and the EM algorithm for
      efficient solution of multidimensional FMM fitting problems. We compare our
      algorithm to the self-annealing EM-algorithm and a standard real coded genetic
      algorithm with the voxel classification tasks within the brain imaging. The
      algorithms are tested on synthetic data as well as real three-dimensional image
      data from human magnetic resonance imaging, positron emission tomography, and
      mouse brain MRI. The tissue classification results by our method are shown to be
      consistently more reliable and accurate than with the competing parameter
      estimation methods.

PMID- 17518066
TI  - Learning-based segmentation framework for tissue images containing gene
      expression data.
AB  - Associating specific gene activity with functional locations in the brain results
      in a greater understanding of the role of the gene. To perform such an
      association for the more than 20 000 genes in the mammalian genome, reliable
      automated methods that characterize the distribution of gene expression in
      relation to a standard anatomical model are required. In this paper, we propose a
      new automatic method that results in the segmentation of gene expression images
      into distinct anatomical regions in which the expression can be quantified and
      compared with other images. Our contribution is a novel hybrid atlas that
      utilizes a statistical shape model based on a subdivision mesh, texture
      differentiation at region boundaries, and features of anatomical landmarks to
      delineate boundaries of anatomical regions in gene expression images. This atlas,
      which provides a common coordinate system for internal brain data, is being used
      to create a searchable database of gene expression patterns in the adult mouse
      brain. Our framework annotates the images about four times faster and has
      achieved a median spatial overlap of up to 0.92 compared with expert segmentation
      in 64 images tested. This tool is intended to help scientists interpret large
      scale gene expression patterns more efficiently.

PMID- 17518067
TI  - Iterative image reconstruction using inverse Fourier rebinning for fully 3-D PET.
AB  - We describe a fast forward and back projector pair based on inverse Fourier
      rebinning for use in iterative image reconstruction for fully 3-D positron
      emission tomography (PET). The projector pair is used as part of a factored
      system matrix that takes into account detector-pair response by using shift
      variant sinogram blur kernels, thereby combining the computational advantages of
      Fourier rebinning with iterative reconstruction using accurate system models. The
      forward projector consists of a 2-D projector, which maps 3-D images into 2-D
      direct sinograms, followed by exact inverse rebinning which maps the 2-D into
      fully 3-D sinograms. The back projector is implemented as the transpose of the
      forward projector and differs from the true exact rebinning operator in the sense
      that it does not require reprojection to compute missing lines of response
      (LORs). We compensate for two types of inaccuracies that arise in a cylindrical
      PET scanner when using inverse Fourier rebinning: 1) nonuniform radial sampling
      and 2) nonconstant oblique angles in the radial direction in a single oblique
      sinogram. We examine the effects of these corrections on sinogram accuracy and
      reconstructed image quality. We evaluate performance of the new projector pair
      for maximum a posteriori (MAP) reconstruction of simulated and in vivo data. The
      new projector results in only a small loss in resolution towards the edge of the
      field-of-view when compared to the fully 3-D geometric projector and requires an
      order of magnitude less computation.

PMID- 17518068
TI  - In the balance: the shift from hospitals into the community.

PMID- 17518069
TI  - Transforming lives.
AB  - Being locked up in a young offender institution causes stress to inmates that can
      erupt into disorder and violence. Two nurses are providing relaxation and
      acupuncture therapies to help them cope.

PMID- 17518070
TI  - Ready for Wembley.
AB  - As the new Wembley Stadium prepares to host its first big football matches and
      rock concerts this summer, local healthcare workers are planning how they will
      cope with any major disaster.

PMID- 17518071
TI  - In search of happiness.
AB  - Unlike other 'talking' therapies, psychotherapy centres on transferance. While it
      can be a painful experience, people feel and function better for it.

PMID- 17518072
TI  - Older patients have much to teach us.

PMID- 17518073
TI  - Adverse drug reactions: reducing the burden of treatment.
AB  - This article offers definitions and descriptions of adverse drug reactions and
      the associated burden of treatment. Nurse-led patient monitoring may be one way
      to minimise the problems attributed to well-known adverse drug reactions. While
      clinical research is needed to explore feasible strategies to ameliorate the
      known adverse effects of treatments, academics need to develop detailed research
      databases to uncover the less well-established adverse effects, which may be of
      considerable public health importance.

PMID- 17518074
TI  - Terminal sedation: promoting ethical nursing practice.
AB  - This article discusses ethical aspects of 'terminal sedation' in relation to end
      of-life care. An examination of the literature reveals there are different
      definitions and explanations of terminal sedation. Some definitions appear
      compatible with the values of palliative care and nursing, whereas others could
      arguably be perceived as deserving of the term 'euthanasia in disguise'. The
      authors suggest that 'palliative sedation' is a more helpful term and argue that,
      when defined and understood appropriately, it is a defensible and ethical
      practice. Nurses should be clear about the purpose of their profession, honest
      about their intentions and respect the autonomy and dignity of the patients for
      whom they provide care. The doctrine or principle of 'double effect' has been put
      forward to support the practice of terminal sedation. The authors examine this
      doctrine and caution that nurses and other professions need to approach it
      critically in relation to terminal sedation. Vignettes are used to illustrate
      aspects of the discussion.

PMID- 17518075
TI  - Understanding Parkinson's disease.
AB  - This article describes the signs and symptoms of Parkinson's disease and the
      complications that arise as the condition progresses. Motor and non-motor
      symptoms are discussed as well as the problems that patients experience on
      admission to hospital. The complexities of medication management--including
      issues of concordance--are outlined and advice is given on how nurses can help
      patients and their carers to manage this condition.

PMID- 17518077
TI  - Remember and learn.

PMID- 17518076
TI  - Tissue viability.

PMID- 17518078
TI  - Sight savers on wheels.

PMID- 17518079
TI  - Leprosy.

PMID- 17518080
TI  - Community dermatology inclusive of leprosy: its past present and future.
AB  - The archives of leprosy and its global history are currently evolving in Oxford.
      A collection of documents and books are housed in the historical library of Sir
      William Osler under the heading of 'Public Health before and after Osler' and the
      history of leprosy can be found on http://www.leprosyhistory.org. A striking
      feature of the old books is their attention to the designation 'Lepra' and the
      evolution of not just leprosy but of the other differential diagnoses of the
      eighteenth and nineteenth century such as psoriasis.. Even in the twentieth
      century, the development of a major interest in Oxford led by Weddell was the
      innervation of the skin first in psoriasis and then in leprosy, joint meetings
      with Weddell, Cochrane, Browne, Rees and others over patients with leprosy, to
      the building of the Cochrane Annex and the work of Colin MacDougal in the
      Department of Dermatology.

PMID- 17518081
TI  - A public health approach for leprosy detection based on a very short term
      training of primary health care workers in basic dermatology.
AB  - INTRODUCTION: In countries where leprosy control is integrated to general heath
      services, health workers, at primary health care level, often manage a large
      number of patients with skin diseases including leprosy. The distinction of
      leprosy from others skin diseases requires more skill and attention. Basic
      dermatological knowledge will help these staff to provide a better quality of
      care. A few years ago, a short term training programme focussed on leprosy and
      some common skin diseases was set up in Mali through a pilot project. This study
      will evaluate the impact of this training on the detection of leprosy at primary
      health care level. METHODS: health care workers from two health districts were
      invited to participate in the training. Trainee was submitted to an anonymous
      written test before training, immediately after and 12-18 months post-training
      using a standardized scoring system. The suspected or referred leprosy cases
      before and after training were compared. Data were recorded and analysed with the
      software Epi info version 6.04. RESULTS: Overall, 495 HCW attended the three
      anonymous written tests (before training, just after and 12-18 months later). The
      proportion of participants who gave correct answers before training, just after
      were respectively: 33 and 57% for correct diagnosis, 5 and 39% for test of
      sensation and 28 and 47% for referral. Eight patients suspected of leprosy were
      referred for further examination; in these, five cases of leprosy were detected.
      DISCUSSION: The training showed a huge improvement in the skill of the
      participants in managing leprosy patients. This study addresses how leprosy
      control can be improved by involving primary health care staff and by the
      implementation of only a single day's training on basic dermatology. CONCLUSION:
      The role of the dermatologist in this post-elimination era of leprosy needs to be
      reconsidered and adapted to the increasing need to take multiple programmes,
      inclusive of dermatology and leprosy, into primary health care services and those
      interested in leprosy control should fund these programmes.

PMID- 17518082
TI  - Role of dermatologists in leprosy elimination and post-elimination era: the
      Brazilian contribution.
AB  - Dermatologists in Brazil have always been involved in care of leprosy patients,
      and have been alternating with public health physicians in the management of
      control policies. It is worth mentioning that Fernando Terra, founder of the
      Brazilian Society of Dermatology (BSD) in 1912, established the position of
      intern dermatologist at the Hospital dos Lizaros, in Rio de Janeiro, in 1913
      (Souza-Araujo, 1952; Oliveira, 1991). In 1920, the dermatologist Eduardo Rabello
      formulated the first national public policy on the control of leprosy in the
      country, which was called 'Inspection of Prophylaxis of Leprosy and Venereal
      Diseases'. His son was an enthusiast of dermatological research and his main
      legacy was the polarity concept of leprosy (Rabelo, 1937). However, from 1930 to
      1985, the public health physicians were in charge of the political guidelines
      that represented the period of establishing the vertical programmatic structure,
      with compulsory isolation of patients (1933-1962). Moreover, the federal states
      coordinated the control actions, based on the leprosy prophylaxis campaign. The
      dermatologists resumed the conduction of the control process in 1986, when multi
      drug therapy (MDT) was implemented in the country, and in 1991, when
      decentralization of public healthcare services to the municipal level took place.
      In 2003 again, the dermatologists were no longer in control of the national
      policy. However, active dermatologists have acted in Brazilian references on
      diagnosis and treatment of Hansen's disease, at municipal, state and national
      levels. It is true that dermatologists have been getting away from leprosy
      control actions. And one could ask: who will replace this specialist? In the
      'post-elimination' era, when the public primary healthcare technicians no longer
      consider leprosy of much significance, the knowledge of the expert in this
      disease and its differential diagnoses will be crucial.

PMID- 17518083
TI  - The leprosy problem--back to the dermatologists.

PMID- 17518084
TI  - Role of dermatologist in leprosy elimination and post-elimination era.

PMID- 17518085
TI  - Dermatologist's role in leprosy elimination/ post-elimination.

PMID- 17518086
TI  - Potential role of dermatologists and dermatological services in developing and
      sustaining the leprosy control referral system in resource constrained settings.
AB  - General Health Services that pay due attention to the management of skin
      conditions are opportune for suspecting and diagnosing early leprosy. In many
      developing countries, patients with dermatological conditions can only access
      specialist services in the larger cities and university hospitals; unaffordable
      costs make the services even less accessible if they can only be provided in the
      private sector. The high profile of dermatologists in the health services, gives
      them the opportunity to facilitate the development and implementation of a
      referral system that includes leprosy. This potential benefit for leprosy control
      must be initiated by current National Leprosy Programme Managers through
      establishing formal relationships with the dermatologists and involving them and
      other partners in the re-designing of leprosy control strategies to keep them in
      tandem with changing epidemiological patterns, national policies and on -going
      health sector reforms. The same health service managers should avail of the
      opportunities from the dermatologists (both in public and private sectors) about
      the current knowledge on the management and control of leprosy.

PMID- 17518087
TI  - Leprosy free India: clinical perspectives and challenges ahead.

PMID- 17518088
TI  - Role of dermatologist in post-leprosy elimination era.

PMID- 17518089
TI  - Role of dermatologists in leprosy elimination and post-elimination era.
AB  - Would it not have been better to have left out the word 'elimination' altogether
      in the question and do what WHO has done in its new strategic plan for 2006-2010,
      'Global Strategy for further reducing the Leprosy Burden and Sustaining Leprosy
      Control Activities'? Why not use a title such as 'The Role of Dermatologists in
      reducing the Leprosy Burden and Sustainig Leprosy Control Activities'? Some
      elements of the 'foundation' of the elimination policy have been (and are still)
      very controversial, its definition and the unsubstantiated (up till now) claim
      that when reaching a prevalence rate of less than 1 per 10,000, the transmission
      of the infection would be interrupted and the incidence would therefore decline.

PMID- 17518090
TI  - Role of a dermatologist in the post-elimination era.

PMID- 17518091
TI  - Role of dermatologists in leprosy elimination and post-elimination era in India.

PMID- 17518092
TI  - Histoid leprosy as reservoir of the disease; a challenge to leprosy elimination.

PMID- 17518093
TI  - Role of dermatologists in leprosy elimination and in the post-elimination era.

PMID- 17518094
TI  - Role of dermatologists in leprosy.

PMID- 17518095
TI  - Role of dermatologists in leprosy elimination and post elimination era.

PMID- 17518096
TI  - Dermatologist. Treating leprosy.

PMID- 17518097
TI  - A focus on the issues associated with implementing self-care as an intervention.

PMID- 17518098
TI  - Rapid survey on case detection of leprosy in a low endemic situation, Zhucheng
      County, Shandong Province, The People's Republic of China.
AB  - The prevalence of leprosy fell below 1 per 100,000 in Shandong province in 1994.
      Since then, a few incident leprosy cases have been reported each year over the
      past 10 years. In order to explore whether or not the reduction in case detection
      in the province was due to the stopping of active case-finding activities, a
      rapid village survey was conducted in a formerly endemic county, using skin
      disease service. Ninety-one villages in 23 townships, covering a total population
      of 104,885, were surveyed. No leprosy case was detected. The results of the
      survey, along with other evidences, such as higher MB/PB ratio among newly
      detected cases and late onset of the disease, suggest that leprosy is dying out
      as a disease in the county as well as in Shandong. The efforts of the leprosy
      control programme should shift to other services such as prevention of disability
      and care for the disabled.

PMID- 17518099
TI  - The ML flow test as a point of care test for leprosy control programmes:
      potential effects on classification of leprosy patients.
AB  - OBJECTIVE: To evaluate the use of the ML Flow test as an additional, serological,
      tool for the classification of new leprosy patients. DESIGN: In Brazil, Nepal and
      Nigeria, 2632 leprosy patients were classified by three METHODS: : (1) as
      multibacillary (MB) or paucibacillary (PB) according to the number of skin
      lesions (WHO classification), (2) by slit skin smear examination, and (3) by
      serology using the ML Flow test detecting IgM antibodies to Mycobacterium leprae
      specific phenolic glycolipid-I. RESULTS: The proportion of MB leprosy patients
      was 39.5, 35.6 and 19.4% in Brazil, Nepal and Nigeria, respectively. The highest
      seropositivity in patients was observed in Nigeria (62.9%), followed by Brazil
      (50.8%) and Nepal (35.6%). ML Flow test results and smears were negative in 69.1
      and 82.7% of PB patients, while smears were positive in 58.6% of MB patients in
      Brazil and 28.3% in Nepal. In MB patients, both smears and ML Flow tests were
      negative in 15.6% in Brazil and 38.3%, in Nepal. Testing all PB patients with the
      ML Flow test to prevent under-treatment would increase the MB group by 18, 11 and
      46.2% for Brazil, Nepal and Nigeria, respectively. Using the ML Flow test as the
      sole criterion for classification would result in an increase of 11.3 and 43.5%
      of patients requiring treatment for MB leprosy in Brazil and Nigeria,
      respectively, and a decrease of 3.7% for Nepal. CONCLUSIONS: The ML Flow test
      could be used to strengthen classification, reduce the risk of under-treatment
      and minimize the need for slit skin smears.

PMID- 17518100
TI  - Laryngeal lesion in leprosy and the risk of aspiration.
AB  - Leprosy affects the larynx, damaging its mucosa and sensory nerves and loss of
      sensation may result in aspiration of food and secretions. The laryngeal lesion
      may be insidious. Post-mortem studies showed bronchopneumonia that could have
      originated from aspiration. In patients with laryngeal symptoms, dysphagia or
      aspiration pneumonia loss of laryngeal sensation should be looked for.

PMID- 17518101
TI  - Focus and VP ellipsis.
AB  - In spoken English, pitch accents can convey the focus associated with new or
      contrasted constituents. Two listening experiments were conducted to determine
      whether accenting a subject makes its predicate a more tempting antecedent for an
      elided verb phrase, presumably because the accent helps focus the subject of the
      antecedent clause, increasing its likelihood of contrasting with the subject of
      the elided clause. The results of Experiment 1 supported the predictions of this
      "Contrasted Remnant hypothesis" but in principle could also be caused by
      listeners avoiding antecedents containing a focused (F-marked) constituent.
      Experiment 2 disconfirmed the hypothesis that listeners avoid antecedents
      containing a focused constituent, although pitch accents within a potential
      antecedent VP affected ellipsis resolution.

PMID- 17518102
TI  - Perceptual distortions in the adaptation of English consonant clusters: syllable
      structure or consonantal contact constraints?
AB  - We present the results from an experiment that tests the perception of English
      consonantal sequences by Korean speakers and we confirm that perceptual
      epenthesis in a second languge (L2) arises from syllable structure restrictions
      of the first language (L1), rather than linear co-occurence restrictions. Our
      study replicates and extends Dupoux, Kakehi, Hirose, Pallier, & Mehler's (1999)
      results that suggested that listeners perceive epenthetic vowels within
      consonantal sequences that violate the phonotactics of their L1. Korean employs
      at least two kinds of phonotactic restrictions: (i) syllable structure
      restrictions that prohibit the occurence of certain consonants in coda position
      STRUCTURE (e.g., *[c.], *[g.]), while allowing others (e.g., [k.], [l.]), and
      (ii) consonantal contact restrictions that ban the co-occurrence of certain
      heterosyllabic consonants (e.g., *[k.m]; *[l.n]) due to various phonological
      processes that repair such sequences on the surface (i.e., /k.m/ --> [n.m];
      /ll.n/ --> [l.l]). The results suggest that Korean syllable structure
      restrictions, rather than consonantal contact restrictions, result in the
      perception of epenthetic vowels. Furthermore, the frequency of co-occurrence
      fails to explain the epenthesis effects in the percept of consonant clusters
      employed in the present study. We address questions regarding the interaction
      between speech perception and phonology and test the validity of Steriade's (2001
      a,b) Perceptual-Mapping (P-Map) hypothesis for the Korean sonorant assimilation
      processes. Our results indicate that Steriade's hypothesis makes incorrect
      predictions about Korean phonology and that speech perception is not isomorphic
      to speech production.

PMID- 17518103
TI  - The role of additional processing time and lexical constraint in spoken word
      recognition.
AB  - Three phoneme monitoring experiments examined the manner in which additional
      processing time influences spoken word recognition. Experiment 1a introduced a
      version of the phoneme monitoring paradigm in which a silent interval is inserted
      prior to the word-final target phoneme. Phoneme monitoring reaction time
      decreased as the silent interval increased indicating that lexical knowledge was
      utilized more effectively with additional processing time. Experiment 1b used
      short, medium, and long words and derived nonwords with word-initial mismatching
      segments. Phoneme monitoring response times to words and nonwords were sensitive
      to both additional processing time (silent interval delay) and word length.
      Experiment 2 examined the utilization of anticipatory coarticulation as a
      function of word length and additional processing time. The results suggest that
      (segmental and coarticulatory) information subsequent to mismatching information
      influences spoken word recognition in a manner dependent on word length and
      availability of additional processing time.

PMID- 17518104
TI  - Perceptual tests of rhythmic similarity: I. Mora rhythm.
AB  - Listeners rely on native-language rhythm in segmenting speech; in different
      languages, stress-, syllable- or mora-based rhythm is exploited. The rhythmic
      similarity hypothesis holds that where two languages have similar rhythm,
      listeners of each language should segment their own and the other language
      similarly. Such similarity in listening was previously observed only for related
      languages (English-Dutch; French-Spanish). We now report three experiments in
      which speakers of Telugu, a Dravidian language unrelated to Japanese but similar
      to it in crucial aspects of rhythmic structure, heard speech in Japanese and in
      their own language, and Japanese listeners heard Telugu. For the Telugu
      listeners, detection of target sequences in Japanese speech was harder when
      target boundaries mismatched mora boundaries, exactly the pattern that Japanese
      listeners earlier exhibited with Japanese and other languages. The same results
      appeared when Japanese listeners heard Telugu speech containing only codas
      permissible in Japanese. Telugu listeners' results with Telugu speech were mixed,
      but the overall pattern revealed correspondences between the response patterns of
      the two listener groups, as predicted by the rhythmic similarity hypothesis.
      Telugu and Japanese listeners appear to command similar procedures for speech
      segmentation, further bolstering the proposal that aspects of language
      phonological structure affect listeners' speech segmentation.

PMID- 17518105
TI  - Does horse activate mother? Processing lexical tone in form priming.
AB  - Lexical tone languages make up the majority of all known languages of the world,
      but the role of tone in lexical processing remains unclear. In the present study,
      four form priming experiments examined the role of Mandarin tones in constraining
      lexical activation and the time course of the activation. When a prime and a
      target were related directly in form (e.g., lou3 'hug'--lou2 'hall'), competitors
      that differed from the prime in tone failed to be activated, indicating the use
      of tonal information to distinguish between segmentally identical words. When a
      prime and a target were not form-related but were related through a third word
      that was not actually presented (e.g., lou3 'hug'--jian4zhu0 'building', where
      lou3 is form-related to lou2 'hall', which was semantically related to
      jian4zhu0), a mismatch in tone prevented activation of minimal tone pairs at
      250ms interstimulus interval (ISI) but did not prevent activation at 50 ms ISI.
      These results indicate that tonal information is used on-line to reduce the
      number of activated candidates, but does not prevent the minimal tone pairs from
      being activated in the early phase of lexical activation.

PMID- 17518106
TI  - The acoustic correlates of perceived masculinity, perceived femininity, and
      perceived sexual orientation.
AB  - Previous studies have shown that a subset of gay, lesbian, and bisexual (GLB) and
      heterosexual adults produce distinctive patterns of phonetic variation that allow
      listeners to detect their sexual orientation from audio-only samples of read
      speech. The current investigation examined the extent to which judgments of
      sexual orientation from speech are related to judgments of masculinity or
      femininity made by an independent group of listeners. It also examined the
      acoustic measures that predict perceived sexual orientation and perceived
      masculinity/femininity. Ten listeners judged the perceived masculinity or
      femininity of 44 talkers (11 heterosexual men, 11 heterosexual women, 11 gay men,
      and 11 lesbian or bisexual women). These were compared to measures of the
      talkers' perceived sexual orientation, and to acoustic measures of the talker's
      speech. Listeners judged gay men to sound less masculine than heterosexual men,
      and lesbian/bisexual women to sound less feminine than heterosexual women. These
      measures were significantly correlated with measures of perceived sexual
      orientation. Regression analyses showed that different sets of acoustic measures
      predicated perceived sexual orientation and perceived masculinity/femininity, and
      that some acoustic measures were more strongly correlated with one perceptual
      measure than the other. Results suggest that perceived sexual orientation,
      perceived masculinity, and perceived femininity are distinct but correlated
      perceptual parameters.

PMID- 17518107
TI  - [Synthesis and antifungal activity of naturally occurring O- and C-prenylated
      flavanones].
AB  - Flavonoids is one of the most important groups of naturally occurring O
      heterocycles possessing a wide range of biological activity. O- and C-prenylated
      flavanones as members of flavonoids also show remarkable biological activity such
      as antibacterial, antiviral, anti-tumor, antifungal, anti-HIV and enzyme
      inhibition activity. O- and C-prenylated flavanones possessing remarkable
      biological activity are representatives of this family of natural products. In
      this paper efficient synthetic methods have been reported for the preparation of
      O-(2, 3) and C-(4, 5) prenylated flavanones isolated from Monotes engleri and
      their analogues (26-30; 38-43) starting from commercially available starting
      materials. In vitro pharmacological examinations of our compounds were performed
      on different Candida species (Candida albicans, Candida inconspicua, Candida
      dubliniensis, Candida krusei) by agardiffusion method. Our structure-activity
      relationship study clearly showed that any modification of the structure of
      selinone (2) and monotesone-A (3) led to the total loss the fungistatic activity.

PMID- 17518108
TI  - [Ecdysteroid sources in the Carpathian basin. 11-hydroxy substituted ecdysteroids
      from the Serratula wolffii Andrae].
AB  - Seven ecdysteroids have been isolated from the methanolic extract of the herb
      Serratula wolffii Andrae. The isolation process involved the removal of polar and
      apolar contaminants, and also included the separation of the target ecdysteroids
      from each other by using combined chromatographic methods. Isolation of the pure
      compounds required a minimum of 2 and a maximum of 7 consecutive chromatographic
      steps with different selectivity. Six of the isolated ecdysteroids showed the
      presence of an 11alpha-hydroxyl group on the steroidal skeleton, which structure
      may enhance the increasing effect of ecdysteroids on the protein synthesys of
      mammals, according to literature data. Ajugasterone C, one of these compounds was
      found to be present in remarkable amount in the plant. One ecdysteroid, 11 alpha
      hydroxypoststerone was identified as a new natural compound.

PMID- 17518109
TI  - [Gas chromatography for analysis of essential oils. Characteristics of essential
      oil of Dracocephalum species and the influence of extraction method on its
      composition].
AB  - In this work the essential oil composition of some less known Dracocephalum
      species was studied and compared the effectiveness, selectivity and influence of
      different extraction methods (hydrodistillation, Soxhlet extraction with organic
      solvents and supercritical fluid extraction) on essential oils. For
      investigations in Hungary and Transylvania cultivated plant material was used.
      The analysis of essential oils was carried out by GC and GC-MS methods. The
      components were identified by standard addition, retention factors and mass
      spectra. The percentile evaluation of each volatile constituents was made on
      basis of GC-FID chromatograms. The accuracy of measurements was characterized by
      relative standard deviation. In the essential oil of D. renati Emb. (studied
      firstly by us) 18.3% of limonene was measured and carvone, citrals and linalyl
      acetate monoterpenes, methyl chavicol and some sesquiterpene (e.g.
      bicyclovetivenol) determined in lower quantities. We established that more than
      50% of essential oil of D. grandiflorum L. was formed by sesquiterpenes (beta
      caryophyllene and- oxide, beta-bourbonene, beta-cubebene, aromadendrene) and the
      essential oil of D. ruyschiana L. contained pinocamphone isomers in more than
      60%. The oxygenated acyclic monoterpenes, the characteristic constituents of
      Moldavian dragonhead were present in some tenth percent only in D. renati oil. We
      found significant differences in the composition of the SFE extract and
      traditional essential oil of D. moldavica L. The supercritical fractions
      collected at the beginning of the extraction process were richer in valuable
      ester component (geranyl acetate) than the essential oil obtained by
      hydrodistillation. The fractions collected at the end of supercritical were poor
      in oxygenated monoterpenes but rich in minor compounds of traditional oil, e.g.
      palmitic acid.

PMID- 17518110
TI  - [Medicinal plant research and phytochemical traditions of Pecs].
AB  - The authors have summarized the local history of pharmacobotany, phytochemistry
      and pharmacognosy remembering Szabolcs Nyiredy, the honorary professor of Pecs
      University.

PMID- 17518111
TI  - [Chemical diversity of the biological active ingredients of salvia officinalis
      and some closely related species].
AB  - Comparative studies on the volatile and non-volatile fractions of 6 species. i.e.
      Salvia officinalis, S. tomentosa, S. fruticosa, S. candelabrum, S. ringens, S.
      lavandulifolia of the Section Salvia (Lamiaceae) have been carried out. Both
      fractions provide the chemical pattern matches to the chemotaxonomic character of
      Subfamily Nepetoideae in Erdtmanr two subfamiliar system. S. lavandulifolia had
      the highest essential oil content, followed by S. fruticosa, S. tomentosa, S.
      officinalis and S. candelabrum. S. ringens contains volatile oil only in traces.
      The neurotoxin thujone content was the highest in the S. officinalis oils and in
      that of S. fruticosa. No thujone was detected in S. lavandulifolia. The other
      species, e.g.: S. tomentosa contain this compound only in moderate concentrations
      (less than 10%). Among the non-volatile fractions of the plant ingredients the
      triterpene ursolic and oleanolic acids had the highest concentration in the
      leaves. Despite some rare cases, ursolic acid dominates the tritepene fraction.
      Rosmarinic and caffeic acids were measured in similar concentrations, in all
      species. As the case of S. officinalis shows, these compounds vary significantly
      in all organs during the vegetation period. Caffeic acid is also ubiquitous in
      the genus Salvia but as our data suggest it occurs in an order of magnitude lower
      concentration than rosmarinic acid. The isolation of phenylethanolid martynoside,
      though obtained in a rather small concentration, is of great chemotaxonomic
      significance, as this is the first phenylethanolid type glycoside isolated not
      only from the Salvia genus but also from the entire Subfamily Nepetoideae. As
      pheylethanolids are rather common and accumulate in significant concentrations in
      plants of the Subfamily Lamioideae, our opinion that the chemical differences
      between the two subfamilies are less qualititative than quantitative, is
      confirmed. This holds true of other chemical markers like monoterpenes, ursolic
      and oleanolic acids, caffeic acid and now phenylethanolids. Diterpenes i.e. 7
      methyl carnosoate, rosmanol 7- methylether, sageon from S. officinalis, 7alpha
      acetoyroyleanone, 7alpha-hydroxyroyleanone, royleanone, 6,7-dehydroroyleanone
      from S. tomentosa and candesalvoquinone, candelabroquinone, 12-O
      methylcandesalvone, candesalvone B methyl ester and candelabrone have been
      isolated from Salvia candelabrum. All of the compounds belong to the abietane
      type of diterpenoids and have pronounced antioxidant effect.

PMID- 17518112
TI  - [Formation of flavanolignane in the white-flowered variety (Szibilla) of Silybum
      marianum in relation to fruit development].
AB  - In our present work we studied the white-flowered lady's thistle variety
      'Szibilla' improved by our Institute and having received state acknowledgement in
      1997. During our investigations we established the following facts: -
      flavanolignanes having liver-protecting, cytoprotective effects can be found only
      in the developing and ripe achene fruits. The vegetative organs contain
      flavanoids of different types; --around the tissues of the fruit (Silybi mariani
      fructus) known as drug raw material for therapy and the pharmaceutical industry,
      effective agents are contained only in the fruit wall having undergone
      significant changes as well as in the woody (ligneous) seed-coat. The endosperm
      and the plant embryo contain effective agents only in traces; --during
      ontogenesis--following the pistil's organization into fruit and seed,
      respectively--we revealed that the biogenesis and accummulation of
      flavanolignanes correlate with the wood formation (lignification) of the seed
      coat.

PMID- 17518113
TI  - [Role of formaldehyde and its reaction products in mechanism of action of some
      plant ingredients].
AB  - BioArena as a complex bioautographic system was successfully used for studying
      mechanism of action of some characteristic plant ingredients (e.g., 1'-methyl
      ascorbigen, trans-resveratrol, salicylic acid, cinnamic acid). It has been
      established that the formaldehyde as a main component of formaldehyde cycle and
      other biochemical pathways can be studied in chromatographic spots as well. Ozone
      as a specially reactive reaction product of formaldehyde can be measured
      indirectly there. Different formaldehyde-capturing and -giving molecules and
      other compounds influenced (inhibited or promoted) characteristically the
      antibiotic effect.

PMID- 17518114
TI  - [In vitro studies on ciprofloxacin-milk interaction using LC-MS methode].
AB  - As fluoroquinolone antibiotics are known to interact with foods containing
      multivalent ions, dairy products represent a risk for less than optimal
      absorption of them. A number of studies give evidence that fluoroquinolones
      forming slightly soluble complexes with metal ions of foods show reduced
      bioavailability. Our aim was to investigate the in vitro dissolution profile of a
      marketed ciprofloxacin (CPFX) containing tablet in aqueous and low fat milky
      mediums. For our experiments three various pH values were chosen to represent the
      circumstances of the gastrointestinal tract. Solid phase extraction (SPE) sample
      preparation followed by high performance liquid chromatography coupled mass
      spectrometry (LC-MS) technique was used to determine the amount of free CPFX.
      According to our results the presence of milk decreases the amount of
      bioavailable CPFX.

PMID- 17518115
TI  - [Fundamentals of stationary phase optimized selectivity LC (SOS-LC)].
AB  - A new procedure (SOS-LC) is described for the optimization of the HPLC stationary
      phase, using serially connected columns and the principle of the "PRISMA" model.
      In the course of the base measurements the retention factors (k) of the analytes
      were determined on three different base stationary phases; other parameters were
      fixed. By use of these data the k values were predicted in the cases of all
      theoretically combined stationary phases. These predictions resulted in numerous
      intermediate theoretical separations but only the optimal one was compiled and
      tested applying other parameters fixed as in the case of the base measurements.
      The overall selectivity of this separation was better than that of any individual
      stationary phase. SOS-LC is independent of the mechanism and the scale of
      separation and will be very advantageous in the case of hyphenated techniques (LC
      MS and LC-NMR) due to stable mobile phase background.

PMID- 17518116
TI  - Economic incentives and barriers to quality care.

PMID- 17518117
TI  - Why we need to certify dialysis technicians.

PMID- 17518118
TI  - Black churches, diabetes groups team up for diabetes awareness.

PMID- 17518119
TI  - Custom-made Raster method improves access surveillance.

PMID- 17518120
TI  - Renal care in Cuba: challenges and opportunities. Part 2.

PMID- 17518121
TI  - Medically stable, mentally static, physically restrained: positive results for
      older transplant recipients.

PMID- 17518122
TI  - Evaluating patients' perceptions of end-stage renal disease.
AB  - Patients not adhering to hemodialysis treatment is a pervasive problem in the
      renal community. We need to identify renal patients' unique needs and incorporate
      these needs into the delivery of dialysis care. The social workers at the USF
      Dialysis Center created and implemented a questionnaire to ascertain patients'
      confidence in and perception of success levels of specific aspects of treatment.
      Nephrology social work interventions to address the issue of non-compliance are
      suggested.

PMID- 17518123
TI  - Managing anemia: what do we do now?

PMID- 17518124
TI  - The FDA, stocks, black boxes and ESAs.

PMID- 17518125
TI  - The FDA black box for EPO: what should nephrologists do?

PMID- 17518126
TI  - Reaction from renal associations. Renal Physicians Association.

PMID- 17518127
TI  - Male circumcision for HIV prevention: evidence and expectations.

PMID- 17518128
TI  - Global policy change and women's access to safe abortion: the impact of the World
      Health Organization's guidance in Africa.
AB  - Along with governments from around the world, African leaders agreed at the
      International Conference on Population and Development (ICPD) in 1994 to address
      unsafe abortion as a major public health problem. At the five-year review of the
      ICPD, they decided further that health systems should make safe abortion services
      accessible for legal indications. Based on this mandate, the World Health
      Organization (WHO) developed norms and standards for quality abortion services,
      Safe Abortion: Technical and Policy Guidance for Health Systems, released in
      2003. While abortion-related maternal mortality and morbidity remains very high
      in many African countries, stakeholders are increasingly using WHO
      recommendations in conjunction with other global and regional policy frameworks,
      including the African Union Protocol on the Rights of Women in Africa, to spur
      new action to address this persistent problem. Efforts include: reforming
      national laws and policies; preparing service-delivery guidelines and
      regulations; strengthening training programs; and expanding community outreach
      programs. This paper reviews progress and lessons learned while drawing attention
      to the fragility of the progress made thus far and the key challenges that remain
      in ensuring access to safe abortion care for all African women.

PMID- 17518129
TI  - [Maternal deaths audit in four Benin referral hospitals: quality of emergency
      care causes and contributing factors].
AB  - OBJECTIVE: Analyse evolution of maternal deaths and quality of emergency
      obstetric care provided to the women admitted in four Benin referral maternities
      thus causes and reasons of deficiencies contributing to maternal death. A
      transversal retrospective study was conducted in two stage: evolution of maternal
      death ratio added to living births was analysed from 1994 to 2003, followed by
      extensive analysis of maternal death in 2003. Different hospital data recording
      and individual interviews were the main sources of data collecting. Maternal
      mortality ratio in hospitals didn't evolve since 10 years. The poor quality of
      care was noticed in 59 % of cases. Direct obstetric causes were prevailing in 74%
      of cases and the leading specific causes were haemorrhage (32,2%), infection
      (31,60%). Deficiencies in health system, medicals errors in treatment and
      monitoring, patients' financial unavailability and inadequate management of
      septic abortions were the main contributing factors. Maternal deaths continue to
      happen unacceptably in Benin. The drastic solutions have to be taken at all
      levels to improve maternal health.

PMID- 17518130
TI  - HIV-1 infection and fertility in Dar es Salaam, Tanzania.
AB  - The objective of this study was to examine the association of HIV-1 infection
      with rates of pregnancy and pregnancy loss in Dar es Salaam, Tanzania. A
      retrospective cohort study of 1,006 HIV-infected women and 485 uninfected women
      was employed. In multivariate analyses controlling for other predictors of
      pregnancy, the association of HIV-seropositivity with a woman's reported number
      of pregnancies was of borderline significance (RR = 1.13, 95% CI = 1.00, 1.27).
      HIV infection was not associated with pregnancy loss in multivariate analysis.
      The adjusted pregnancy rate ratio comparing HIV-positive women at the earliest
      stages of infection to all uninfected women was 1.22 (95% CI = 1.04, 1.42). HIV
      infection was not associated with female fertility when comparing women in the
      most advanced stages of infection to all uninfected women. We conclude that HIV-1
      infected women had higher pregnancy rates than uninfected women. This association
      disappeared when analyses were limited to women with advanced disease. Abstract
      word count: 150.

PMID- 17518131
TI  - Male knowledge, attitudes, and family planning practices in northern Nigeria.
AB  - This paper examines the linkages between socioeconomic characteristics,
      attitudes, and familial contraceptive use. Past family planning programs in
      Nigeria have been mainly directed toward women. However, because northern Nigeria
      (and to a slightly lesser extent all of Nigeria) remains a patrilineal society
      characterised by early age at marriage for women, men at present continue to
      determine familial fertility and contraceptive decisions. Consequently, at least
      for the time period relevant for current policy planning purposes, the
      willingness of husbands to adopt or allow their spouses to use family planning
      practices will determine the pace of fertility reduction in Nigeria. The results
      suggest that there is high knowledge of contraceptives, a generally negative
      attitude towards limiting family size for economic reasons, and consequently low
      rates of contraceptive use. Respondents who were willing to use contraceptives
      were more willing to use them for child spacing purposes than explicitly for
      limiting family size. Path-analytic decompositions of the effects of predictor
      variables show that education has the largest direct and total effects on
      contraceptive use while specific knowledge of contraceptives has the smallest
      direct and total effect (as well as a paradoxical negative direct effect when
      education is included in the model). Most importantly, attitudes have the largest
      direct effect on contraceptive use with a standardized coefficient value of 781.
      Thus, since knowledge of contraceptive is already high among even those
      respondents who do not use contraceptives, the attitudes of males are especially
      important for decisions about contraceptive use. As a result, family planning
      programs that continue to focus solely on women will continue to achieve only
      limited successes in northern Nigeria (and likely in the many patrilineal
      societies where similar programs are pursued).

PMID- 17518132
TI  - Factors influencing women's choice of place of delivery in rural Malawi--an
      explorative study.
AB  - This explorative study was conducted in the Mangochi area in Malawi with the aim
      of investigating the individual, community and health facility level factors
      influencing women's choice of place of delivery. In depth interviews and non
      participating observation were the methods used. Three major issues were
      revealed. First, sub optimal quality of care including communication, attitudes
      and cooperation within the health care system was identified as a main factor.
      Secondly, cultural aspects such as influence from decision makers, perceptions of
      danger signs and traditional views on pregnancy and delivery were important.
      Finally, an unsatisfactory availability to skilled delivery care in terms of
      distance, transport and costs was shown. We conclude that the barriers to use of
      professional obstetric care in Malawi partly can be attributed to the health care
      system itself, and that a more individualized maternity care is needed.

PMID- 17518133
TI  - Knowledge of HIV/AIDS and sexual practices among adolescents in Benin City,
      Nigeria.
AB  - A cross sectional study to determine the knowledge of HIV/AIDS and sexual
      practices of adolescents was undertaken in Benin City, Nigeria. Benin City the
      capital of Edo State, Nigeria, has 40 government owned secondary schools
      comprising 6 boys, 10 girls, and 24 mixed. Out of these 3 schools were randomly
      selected for survey viz; Adolor (boys only), Iyoba (girls only), Army Day
      (mixed). The sample size for the survey was 920 while the total population for
      selected schools was 1692 giving a sampling ratio of 1:2. Using the systematic
      sampling method and class register as sampling frame every other child was
      selected for the study. However, only 852 students consented to participate
      giving a response rate of 92.6%. An overwhelming majority of the adolescents were
      aware of HIV/AIDS but only 16.2% knew the cause of the disease. The submission
      that kissing, living with infected persons and sharing their utensils could lead
      to infection was an indication of ignorance. Sexual intercourse was the
      predominant route of transmission mentioned by 60.0% while multiple sexual
      partners was prevalent among age group 13-15 years. Playing with sharps, frequent
      clean head shave with unsterilised instruments in the barbing saloon and
      promiscuity were some of the activities that adolescents were involved in that
      could lead to HIV/AIDS infection. In conclusion, the knowledge of the study
      population was poor and correlates with their reckless sexual practices.
      Prevention is the best option to the disease. Better informed youths on HIV/AIDS
      will enhance the principle of prevention.

PMID- 17518134
TI  - Menstruation: symptoms, management and attitude of female nursing students in
      Ibadan, Nigeria.
AB  - This study surveyed 120 student nurses from two schools of nursing in Ibadan,
      Nigeria to assess the symptoms experienced during menstruation, attitude towards
      and management of menstruation. The student nurses overall mean age at menarche
      was 14 years, average duration of menstrual period was five days and mean of
      menstrual cycle was 28 days. Out of the 120 study participants, 93% were having
      menstruation regularly. More participants experienced symptoms during
      premenstrual periods than menstrual periods. Majority (70%) used sanitary pad to
      manage their menstruation, 93% had positive attitude towards menstruation while
      only 20% consulted medical doctors whenever they experienced menstrual symptoms.
      Paracetamol was the drug of choice for many of the participants whenever they
      experienced menstrual symptoms It was recommended that authorities in schools of
      nursing should not overlook reproductive health needs of students. Also teaching
      of reproductive health education early in primary and secondary schools should be
      encouraged.

PMID- 17518135
TI  - Assessing the level of preparedness of private health providers for clinical
      management of HIV/AIDS epidemic in Nassarawa State, Nigeria.
AB  - Very little information is available on the extent to which the private health
      sector is involved in clinical management of HIV/AIDS in Nigeria. This study
      assessed the potentials and existing capacity of 15 private health facilities in
      Nassarawa state for clinical management of HIV/AIDS. Information was obtained
      from 25 staff (15 proprietors and 10 professionals) of the randomly selected
      health facilities in the state using structured questionnaire. Of the 15 health
      facilities, three provided voluntary counselling and testing (VCT), seven had
      never admitted persons living with HIV/AIDS (PLWHA), two provided laboratory
      services, none provided home-based care for PLWHAs, two had anti-retro-viral
      drugs in stock, two had rooms for counselling, three had full-time doctors, and
      six had registered nurses. Of the 25 health workers, 5 had skills/training in
      conducting VCT, 15 had skills in the treatment of opportunistic infections, 14
      were aware of anti-retro-viral drugs and 13 did not feel comfortable attending to
      PLWHAs. The study recommended capacity building on HIV/AIDS related services for
      the private health-workers.

PMID- 17518136
TI  - Effect of training programme on secondary schools teachers' knowledge and
      attitude towards reproductive health education in rural schools Ile-Ife, Nigeria.
AB  - This study assessed the effect of training programme on teachers' knowledge of
      and attitude towards reproductive health education /sexuality education [RHE/SE]
      in five randomly selected rural schools in Ife-North local government area
      [IFLGA], Southwest, Nigeria. All the 84 teachers in the selected schools in the
      LGA were recruited for the study. They [84 teachers] were all given training in
      RHE/SE for one month. Their knowledge and attitude towards RHE/SE were assessed
      pre-and post-training programme. The results show a significant increase in
      percentage of those who had good knowledge in general areas of RHE/SE at post
      training assessment compared with pre-training assessment[from 14.3% to 53.6%,
      p=0.0001].Also, pre-post attitudinal disposition assessments show that there was
      an increase in percentage of those who were favourably disposed to the teaching
      of RHE/SE in Nigeria Schools at post-training assessment [from 17.9% to 45.2%,
      p=0.0011]. The study suggests that RHE/SE should be included and made compulsory
      in all training programme for all teachers in Nigeria.

PMID- 17518137
TI  - Alloxan-induced and insulin-resistant diabetes mellitus affect semen parameters
      and impair spermatogenesis in male rats.
AB  - The purpose of this study was to determine the effects of diabetes mellitus and
      insulin resistance on semen parameters, histology of reproductive organs and
      serum concentrations of testosterone and luteinizing hormone (LH). Male Sprague
      Dawley rats weighing 180 - 200g were made diabetic by intravenous injection of
      alloxan (40 mg/kg): and insulin resistant by chronic fructose feeding (25%
      fructose) for 12 weeks. Rats were anaesthetized, followed by laparatomy. Blood
      was obtained by cardiac puncture for measurement of testosterone and LH
      concentrations by radioimmunoassay. Semen analysis was carried out; reproductive
      organs were isolated, fixed in Bouin's fluid and processed for histological
      studies. All semen parameters analyzed were significantly reduced (P < 0.05) in
      the diabetic and insulin resistant rats compared to control rats. Body weight and
      weight of reproductive organs were also significantly reduced (P < 0.05).
      Furthermore, tissue fixation studies revealed changes in the cytoarchitecture of
      reproductive organs in the diabetic and insulin resistant rats compared to
      control rats. However, serum concentrations of testosterone and LH were not
      significantly different in all the groups. We conclude that diabetes mellitus and
      insulin resistance affect semen parameters and impair distinct phases of
      spermatogenesis in male rats. Some mechanisms responsible for this impairment are
      suggested.

PMID- 17518138
TI  - Effects of breast cancer and mastectomy on fibrinolytic activity in African
      women.
AB  - Reduced blood fibrinolytic activity (FA) has been postulated in cancer. It is
      good to know if this is also the case in Africans with breast cancer. Africans
      are known to possess enhanced fibrinolysis. This study was designed to assess the
      effect o breast cancer on fibrinolytic activity and the effect of mastectomy on
      fibrinolysis in African women. Sixty histo-patholically proven breast cancer
      patients aged 25 - 45 years were compared with 50 healthy age-matched controls.
      Plasma fibrinogen levels and euglobulin lysis time (ELT) were estimated in breast
      cancer patients and th controls. Patients with breast cancer had significantly
      increased fibrinogen levels euglobulin lysis time (P < 0.001) compare with
      controls. There was significant mean difference between pre and post-mastectomy
      fibrinogen and euglobulin lysis time values (p < 0.05). Progressive significant
      decrease in fibrinogen levels and euglobulin lysis time values (P < 0.05) were
      observed over the weeks studied respectively. African women with breast cancer
      have defective fibrin clearing which could predispose them to thrombotic
      diathesis and early mastectomy may be beneficial. We suggest that fibrinolytic
      components may be a prognostic marker for breast cancer.

PMID- 17518139
TI  - Infertility and migraine in midwest Niger-Delta region.

PMID- 17518140
TI  - Patient comes back to ED in scrubs and works an entire shift as a temp.
AB  - A former patient in a Tampa, FL, ED, returned to the department in scrubs,
      claimed to be a temp, and was allowed to work despite not having any ID. To avoid
      similar problems, your ED should have a well-defined set of rules for people who
      report for work without an ID and/or do not demonstrate the requisite skills to
      treat patients. No badge, no work" is a good rule, unless the person is well
      known to you. All ED staff, including physicians and ancillary workers, should be
      prepared to produce photo ID immediately upon request. If staff cannot reach you,
      they should be encouraged to report interlopers to security or local police, as
      they are guilty of trespassing.

PMID- 17518141
TI  - EDs can play major role in rapid response teams.

PMID- 17518142
TI  - Incremental approach is best with a new EDIS.
AB  - Be aware of how your staff are taking to a new Emergency Department Information
      System, and be prepared to be proactive in terms of spotting problems and
      addressing them to ensure the entire staff is comfortable. Make sure staff
      receive adequate training. Provide them with several sessions if necessary. Once
      a new phase has been implemented, monitor staff performance with computer screen
      audits. Doctors often require more time and patience than nurses, but make sure
      that rejection of the system is not an option.

PMID- 17518143
TI  - Cooperation, expansion keep diversion rate low.
AB  - Having the same diversion policy as neighboring facilities will enhance
      communications during stressful periods and minimize the likelihood that more
      than one ED will go on diversion at the same time. Establish a Code Purple to
      indicate that your ED is at capacity and requires cooperation from other hospital
      departments. Share this information with other facilities, to determine which of
      them might have capacity to accommodate additional patients slated for your ED.
      If no other facilities can accommodate your needs, go on Code Orange (disaster
      alert) rather than on diversion. This will activate your disaster plan and enable
      you to call in extra staff.

PMID- 17518144
TI  - Proposed leadership standard revisions emphasize resolution of conflicts among
      leaders.
AB  - Proposed revisions of Joint Commission leadership standards put the focus on
      conflict resolution. Interdepartmental conflicts can best be resolved through
      collaboration. To minimize conflict within the department, engender a team
      atmosphere among the staff. When conflicts arise, assemble an interdisciplinary
      team involving all affected departments, and seek a solution together. If upper
      management is charged with resolving conflicts, employ your political skills to
      convince administration, risk management, that ED-friendly solutions are best for
      patient welfare. Eliminate hierarchical structure and a hostile atmosphere
      between physicians and nurses to reduce likelihood of personal conflicts.

PMID- 17518145
TI  - White paper underscores patient health literacy.

PMID- 17518146
TI  - Critical lab value reporting more challenging in ED.
AB  - The Joint Commission requires timely reporting of all critical lab values and
      verification by having the person receiving the information read it back and
      confirm it. Because of higher volumes of critical results, this requirement is
      more challenging for EDs than other hospital units. Measure the time frame from
      the nurse becoming aware of the result to the physician being informed. If your
      policy requires documentation of the read-back, make sure it's followed
      consistently. ED nurses can be taken out of the process by having the lab
      communicate with the ED physician directly.

PMID- 17518147
TI  - The Journal of Goldberg Research (April Fool).

PMID- 17518148
TI  - Jefferson consults a British physician.

PMID- 17518149
TI  - Pediatric upper extremity conditions: traumatic and congenital.
AB  - There are a variety of upper extremity conditions both traumatic and congenital
      that the physician will encounter. Some require emergent treatment; some should
      be observed. It is important to make the correct diagnosis and refer in a timely
      fashion.

PMID- 17518150
TI  - Adolescents and upper extremity sports injuries: the throwing arm.

PMID- 17518151
TI  - Idiopathic scoliosis in children: an update.

PMID- 17518152
TI  - Pediatric femur fractures: treatment in the year 2007.

PMID- 17518153
TI  - Transitional care.

PMID- 17518154
TI  - Arthritis and associated health conditions and risks among Rhode Island adults in
      2005.

PMID- 17518155
TI  - Retiree-volunteers and the Abbreviations Study.

PMID- 17518156
TI  - Malignant gastric ulcer on multidetector row CT and endoscopy.

PMID- 17518157
TI  - A well-nourished vocabulary.

PMID- 17518158
TI  - What are we waiting for?

PMID- 17518159
TI  - Screening for chlamydia trachomatis: barriers for homeless young people.
AB  - OBJECTIVE: The study explored homeless young people's knowledge and attitudes of
      Chlamydia trachomatis (Chlamydia) and its screening. DESIGN: Semi-structured
      interviews using focus groups. SETTING: An inner city clinic for homeless young
      people. SUBJECTS: Homeless young people aged 16 -26 years. OUTCOMES: Perceptions
      of Chlamydia and its screening. RESULTS: 19 males and 6 females aged 16-26 years
      participated. Content analysis confirmed a lack of knowledge, prior education and
      misinformation about Chlamydia and barriers to being screened. Ideas for
      informing young people about Chlamydia included advertising on billboards, in
      free newspapers, and improved school sex education programs. CONCLUSIONS:
      Homeless young people have poor knowledge of Chlamydia and its screening and
      barriers to the screening process. Culturally-specific education and health
      promotion programs and services are needed.

PMID- 17518160
TI  - Acceptability of antenatal screening for depression in routine antenatal care.
AB  - OBJECTIVE: The Edinburgh Postnatal Depression Scale (EPDS) is generally
      recognised as a valid, reliable, cost-effective and simple tool to implement
      within routine care, however there is controversy regarding the acceptability of
      screening for depression. This paper aims to examine how acceptable women find
      (1) completing a battery of questionnaires, including the EPDS and (2) receiving
      feedback from midwives regarding the significance of their EPDS score when being
      screened for depression as part of routine antenatal care. DESIGN: Telephone
      interviews with women following completion of the questionnaire battery and
      receiving feedback from midwives. SETTING: Antenatal primary care in a hospital
      setting. SUBJECTS: Community sample of 407 women screened by midwives in
      antenatal clinics. MAIN OUTCOME MEASURES: Information regarding women's
      experience of participating in the screening process. RESULTS: 100% of women
      reported that the screening experience was acceptable and not upsetting. Almost
      50% reported that the screening process raised their awareness of perinatal
      depression. No woman reported feeling stigmatised, labelled or distressed by the
      screening process. Women reported that gaining immediate feedback from midwives
      was reassuring. CONCLUSION: This study strongly supports the acceptability of
      routine screening for perinatal depression in the context of registered midwife
      support.

PMID- 17518161
TI  - Critical care nurses' knowledge in preventing nosocomial pneumonia.
AB  - OBJECTIVE: The purpose of this study was to identify knowledge deficits
      concerning nosocomial pneumonia (NP) prevention among critical care nurses. The
      study also determined whether NP knowledge was associated with nurse
      characteristics. DESIGN: A survey design using a mailed self-administered
      questionnaire. SETTING: New Zealand critical care nurses were identified through
      the Nursing Council of New Zealand. SUBJECTS: 134 critical care nurses. MAIN
      OUTCOME MEASURES: NP prevention knowledge score (the proportion of 24 items
      answered correctly). RESULTS: The NP knowledge score ranged from 21% to 92%. The
      mean (and median) was 48%. Items related to knowledge about NP risks had the
      highest mean score (67%) compared to items addressing NP prevention (43%) or the
      role of devices in the transmission of NP (45%). No nurse demographic or
      workplace characteristic was associated with NP knowledge. CONCLUSIONS: Several
      important deficits in nosocomial pneumonia knowledge were identified indicating a
      need for critical care nurses to have greater exposure to nosocomial pneumonia
      prevention education, guidelines, and research.

PMID- 17518162
TI  - Educational intervention for patients with automatic implantable cardioverter
      defibrillators.
AB  - OBJECTIVE: The aim of this pilot study was to evaluate the feasibility of a brief
      educational intervention administered two weeks after Automatic Implantable
      Cardioverter Defibrillator (AICD) implantation on subsequent levels of anxiety,
      depression, stress and hostility. DESIGN: A randomised controlled design was
      used. SUBJECTS AND SETTING: Twenty-two patients hospitalised for implantation of
      an AICD were recruited for the study. Thirteen patients were randomised to attend
      the intervention and nine to the standard care control group. INTERVENTION: The
      educational intervention was delivered by a nurse and psychologist. It comprised
      one 60-90 minute session in which the patient and a significant other received
      detailed information about the AICD (including practical and psychological
      aspects), and had the opportunity to ask questions, express concerns and receive
      reassurance. MAIN OUTCOME MEASURE: The DASS was used to measure anxiety,
      depression and stress at two, four and six months after AICD insertion. RESULTS:
      Patients who attended the intervention showed no significant improvements or
      trend toward improvement on any of the measured psychological domains.
      CONCLUSIONS: The findings suggest that a single educational session delivered to
      recent AICD recipients is not sufficient to improve patients' psychological
      adjustment.

PMID- 17518163
TI  - The educational needs of nurses working in Australian general practices.
AB  - OBJECTIVE: To describe the educational needs of nurses working in general medical
      practice in Australia. DESIGN: Survey research combining qualitative and
      quantitative data collected via telephone interview. SUBJECTS: 222 enrolled (RN
      Division 2 in Victoria) and registered nurses (RN Division 1 in Victoria) working
      in general practice in rural and urban areas of Australia. RESULTS: Nurses
      identified a number of educational areas of high importance including
      communication skills (94.1%); infection control (93.7%); confidentiality and
      national privacy legislation (93.7%); legal and ethical issues (91.9%); first aid
      and CPR (91.4%); wound (91.0%); care cold chain monitoring (90.0%); sterilisation
      (90.0%); and triage (90%). Barriers to education were identified including lack
      of time due to work (21.9%); costs of courses (17.3%); distance to education
      (13.9%); and lack of time due to family commitments (13.1%). More rural/remote
      nurses identified distance as a barrier (20.5%) than urban nurses (3.6%).
      DISCUSSION: cussion: The education areas that were rated as important by a high
      number of the nurses appeared to relate directly to the activities nurses
      currently undertake in Australian general practice. Barriers to education may
      reflect the workforce characteristics of general practice nurses and/or the
      capacity of general practices to finance training for employees. CONCLUSIONS: As
      a growing specialty of nursing in Australia, general practice nursing should be
      supported by a solid foundation of ongoing education and training that is
      tailored to the current needs of nursing in general practices and reflects
      appropriate delivery options to overcome barriers to training.

PMID- 17518164
TI  - Enrolled nurse skill extension: metropolitan myth or rural reality?
AB  - OBJECTIVE: The objective of this study was to examine whether the position of
      'after hours clinical support enrolled nurse' is embracing clinical skill
      extension in the acute surgical area. DESIGN: Experienced enrolled nurses
      employed in a supernumerary capacity documented all activities with which they
      were engaged over a six-month period. SETTING: Six surgical wards within a
      tertiary referral hospital, Sydney, Australia. SUBJECTS: Enrolled nurses working
      after hours in an extended support role in a supernumerary capacity. RESULTS:
      Data demonstrated that, in this study, the 'after hours clinical support enrolled
      nurse' was primarily performing routine nursing activities. Although the number
      of extended skills (n=13) performed could be considered diverse for an enrolled
      nurse, many were seldom performed. The most frequently performed extended skills
      were patient escorts and undertaking bladder ultrasounds with a mobile scanner.
      Medication administration was rarely performed. CONCLUSION: The role primarily
      incorporates basic nursing care with minimal scope for extended skills. The paper
      recommends that basic nursing practices be delegated to assistants in nursing to
      enable the 'after hours clinical support enrolled nurse' to effectively support
      registered nurses and extend their own practice.

PMID- 17518165
TI  - Burnout in nursing.
AB  - OBJECTIVE: Previous research has suggested that organisational change can
      contribute to stress-related outcomes for workers. Burnout, one such stress
      related outcome, has been conceptualised as a multidimensional construct
      consisting of emotional exhaustion, depersonalisation and reduced personal
      accomplishment. Many health care organisations have undergone substantial
      organisational change over the last decade. The purpose of this study was to
      assess levels of burnout in nurses and to ascertain if there were individual or
      work characteristics that were associated with this syndrome. DESIGN: Randomised
      survey methodology. SETTING: Registered nurses (Division 1) in Victoria who were
      ANF members. SUBJECTS: A random sample of 574 Victorian ANF nurse members. MAIN
      OUTCOME MEASURES: The assessment of levels of burnout in Victorian ANF nurse
      members and the identification of individual or work characteristics that may be
      associated with it. RESULTS: Victorian ANF nurse members exhibited lower
      depersonalisation and higher personal accomplishment compared to medical and
      overall normative data. Increasing age and fewer working hours were associated
      with lower levels of emotional exhaustion and depersonalisation. Working overtime
      was positively associated with emotional exhaustion however further analyses
      demonstrated that those who worked overtime voluntarily did not differ from
      workers not working overtime. However feeling pressured/expected to work overtime
      was positively associated with emotional exhaustion and depersonalisation.
      CONCLUSION: Victorian ANF nurse members were not experiencing high levels of
      burnout. However the study highlighted the need for health care management to
      recognise the importance of working reasonable hours and in particular, to
      understand the potential detrimental effect that having to work pressured or
      unexpected overtime has on staff.

PMID- 17518166
TI  - Adolescent appropriate care in an adult hospital: the use of a youth care plan.
AB  - OBJECTIVE: This paper explores the development of a specific youth care plan
      which provides a framework for adolescent appropriate care in an adult acute care
      facility. SETTING: The Sydney South Western Area Health Service (SSWAHS) Youth
      Consultancy, Royal Prince Alfred Hospital (RPAH), Camperdown, Sydney, Australia.
      SUBJECTS: Young people aged 12- 24 years who were admitted to the acute hospital
      setting at RPAH. Approximately 2500 young people are admitted as in-patients to
      RPAH each year. PRIMARY ARGUMENT: Adolescents are a unique population with
      different developmental and health care needs. Adult acute care facilities are
      often ill-equipped to deal with the complex developmental needs of young people
      and need guidance and education to provide appropriate care for this population.
      Nurses play a pivotal role in caring for hospitalised young people. A
      developmentally relevant youth care plan may be an appropriate and effective tool
      to facilitate best-practice nursing. CONCLUSIONS: The Youth Care Plan was
      developed to provide a framework for developmentally appropriate assessment and
      care for young patients admitted to RPAH. This care plan also provides a
      mechanism for referrals to the Youth Consultancy team, which provides continuous
      education, consultation and liaison for staff related to both the Youth Care Plan
      and general adolescent health. The Youth Care Plan is regularly audited and has
      been trialled as a registered Continuous Quality Improvement project of RPAH.

PMID- 17518167
TI  - The use of the term vulnerability in acute care: why does it differ and what does
      it mean?
AB  - OBJECTIVE: Throughout health care literature, vulnerability is widely accepted as
      a potential issue for all patients yet the consensus on the meaning of and
      practical strategies to reduce or manage these 'harmful agents' in the clinical
      context are rarely offered. Three main themes emerge from the related literature
      which can be further refined into general terms of; social vulnerability--a
      person's basic statistical data in relation to their potential for illness;
      psychological vulnerability--the actual or potential harm to the identity of self
      and/or other emotional effects such as anxiety or stress caused by the ailment or
      treatment; and physical vulnerability--which refers to the actual physiological
      state where an individual is susceptible to further morbidity or mortality.
      SETTING: Acute care facilities. PRIMARY ARGUMENT: Although there is
      acknowledgment within the literature that individuals will experience some form
      of vulnerability when hospitalised, the complexity of what defines vulnerability
      for individuals causes further problems for patients and health professionals
      alike. CONCLUSIONS: This paper attempts to define vulnerability within the
      context of Western health care systems and raises the following issues: all
      states of vulnerability are accurate and appropriate in the context of the study
      or incidence alluded to, but further discussion and research is required to
      achieve a consensus to when, how, why and who is vulnerable. It is this
      recognition of the potentially differing classifications of vulnerability and the
      particular contexts that can be used that may assist nurses and other health care
      professionals with, not only problems associated with a patient's
      hospitalisation, but in the implementation of appropriate strategies to
      individual patient's cases.

PMID- 17518168
TI  - The professional self-concept of nurses: a review of the literature from 1992
      2006.
AB  - OBJECTIVE: This paper will discuss some recent concerns about research in the
      area of the professional self-concept of nurses, and trace the development of the
      literature on professional self-concept of nurses over the last 14 years. PRIMARY
      ARGUMENT: Professional self-concept or how nurses feel about themselves as nurses
      is vital in examining current and future nursing practice and education, as it
      affects patient care. CONCLUSION: The essence of the paper is the identification
      of three streams of literature: (1) which has 'emerged from the development of
      the Professional Self-Concept of Nurses instrument'; (2) literature which fails
      to consider recent or current research in the area; and (3) 'well-conducted work
      in the topic area'. The implications for nurses, educators and students are
      presented.

PMID- 17518169
TI  - [Sugammadex, a revolutionary new drug to reverse neuromuscular block].

PMID- 17518170
TI  - [The Color Analog Scale: a valid instrument for measuring pain intensity in
      Catalan-speaking children?].
AB  - OBJECTIVE: To evaluate the validity of the Color Analog Scale (CAS) for assessing
      pain intensity in a Catalan-speaking pediatric population. PATIENTS AND METHODS:
      We compared children's CAS pain intensity ratings with their scores on the
      Catalan version of the Faces Pain Scale-Revised (FPS-R). We also compared the CAS
      to ratings of affective experience of pain evaluated with the Facial Affective
      Scale (FAS). RESULTS: A total of 124 Catalan-speaking children aged 7 to 15 years
      admitted to the pediatric wards of 3 university hospitals participated in the
      study. The results supported the construct and criterion validity of the CAS in
      the Catalan population. Correlation between CAS and FPS-R scores was high and
      significant (r=0.87; P <.001). Similarly, pain intensity scores correlated
      significantly with emotional discomfort recorded with the FAS (r = 0.34; P <
      .001). Most of the children, regardless of sex or age, reported a preference for
      the FPS-R over the CAS. CONCLUSIONS: The results of the present study provide
      preliminary evidence of the convergent, discriminant, and criterion validity of
      the CAS in this setting. The CAS appears to be valid for measuring pain intensity
      in Catalan-speaking children and adolescents between the ages of 7 and 15 years.

PMID- 17518171
TI  - [Cost-effectiveness analysis of patient-controlled analgesia compared to
      continuous elastomeric pump infusion of tramadol and metamizole].
AB  - OBJECTIVES: Little information is available on the cost-effectiveness of
      postoperative patient-controlled analgesia (PCA). The present study compared PCA
      to continuous infusion by elastomeric pump. MATERIAL AND METHODS: Fifty ASA 1 or
      2 patients undergoing major gynecologic surgery were enrolled for a randomized
      controlled trial to evaluate the effectiveness and costs derived from intravenous
      PCA with metamizole and tramadol compared to continuous infusion of the same
      analgesic solution by elastomeric pump in the 48 hours following surgery. Patient
      satisfaction and side effects were also recorded. RESULTS: The analgesic
      effectiveness and side effects of the 2 regimens were similar, although 61% of
      patients in the elastomeric pump group needed morphine for rescue analgesia
      compared to 33% in the PCA group (P < .05). In the PCA group, 81% of the patients
      said they would repeat the analgesic treatment compared to only 56% in the
      elastomeric pump group (P = .05). The mean number of nursing interventions was 16
      for the PCA group and 19 for the elastomeric pump group. The mean cost of the
      treatment (not including the PCA pump, provided by the manufacturer) was Euros
      41.35 for the PCA group and Euros 56.22 for the elastomeric pump group.
      CONCLUSIONS: The analgesic efficacy of the 2 regimens was similar. However,
      patient satisfaction was greater with PCA and use of an elastomeric pump was more
      expensive. In the setting of the present study, postoperative PCA proved to be
      more advantageous than continuous elastomeric pump infusion.

PMID- 17518172
TI  - [Stress response under continuous infusion of remifentanil compared to bolus
      doses of fentanyl assessed by levels of cytokines, C-reactive protein, and
      cortisol during and after abdominal hysterectomy].
AB  - OBJECTIVES: Surgery and anesthetic method have immunomodulating effects on
      hemodynamic response and stress. We compared the effects of 2 intraoperative
      analgesic regimens on patients undergoing abdominal hysterectomy. MATERIAL AND
      METHODS: We conducted a randomized double-blind trial in ASA 1 and 2 patients
      undergoing abdominal hysterectomy under balanced anesthesia. Twenty-nine patients
      were randomized to 2 groups. One group received analgesia by infusion of
      remifentanil plus morphine and nonsteroidal anti-inflammatory drugs as rescue
      medications; the other received conventional analgesia with bolus doses of
      fentanyl according to changes in hemodynamic variables. We measured levels of
      proinflammatory (interleukin [IL]-6) and antiinflammatory (IL-10) cytokines,
      cortisol, and C-reactive protein preoperatively, at incision, and at 1, 4 and 24
      hours after surgery. RESULTS: There were no significant differences between the 2
      groups in terms of the markers studied at baseline. In each group, however, there
      were significant changes from baseline at the various points in time. IL-6 and IL
      10 levels were significantly elevated (P < .05) at 4 hours. The changes in
      cortisol levels were significantly different at 1 and 4 hours. Finally, there
      were significant increases in C-reactive protein at 24 hours. CONCLUSIONS: Unlike
      other clinical trials, our study detected no differences between the 2 techniques
      in response to surgical stress evaluated by analyzing concentrations of pro- and
      anti-inflammatory cytokines, cortisol, and C-reactive protein.

PMID- 17518173
TI  - [Continuous femoral nerve block to control postoperative pain in outpatient
      orthopedic surgery].
AB  - OBJECTIVE: Postoperative pain is one of the most frequent complications of
      outpatient orthopedic surgery. We therefore studied the efficacy, feasibility,
      and safety of the continuous femoral nerve block as an analgesic technique for
      outpatient anterior cruciate ligament reconstruction. MATERIAL AND METHODS: We
      carried out a single-blind prospective study of ASA 1-2 patients who received a
      continuous femoral nerve block with 0.125% bupivacaine through an elastomeric
      pump to treat postoperative pain as part of a multimodal approach. Postoperative
      pain was assessed on a verbal numerical scale from the immediate postoperative
      period until 48 hours after the operation. Side effects and patient satisfaction
      were also assessed. RESULTS: Sixty-three patients were enrolled. The continuous
      femoral nerve block was effective: in the first 24 hours following surgery 90% of
      patients had mild or no pain, and 92% required no rescue medication. It also
      proved safe, as there were no significant side effects. CONCLUSION: The
      continuous femoral nerve block with 0.125% bupivacaine is a safe, effective
      option for the management of postoperative pain in outpatient anterior cruciate
      ligament reconstruction.

PMID- 17518174
TI  - [Anesthetic and physiologic implications of neurophysiologic monitoring with
      evoked potentials during spinal surgery].
AB  - Neurophysiologic monitoring with somatosensory and motor evoked potentials in
      spinal surgery is now widely applied in order to reduce the risk of neural injury
      and facilitate intraoperative decision making. Most anesthetics affect such
      monitoring by altering both somatosensory and motor evoked responses and these
      effects may place constraints on the choice of anesthetic. Intraoperative
      management includes maintaining stable physiologic conditions, which involves
      adjusting hemodynamic parameters, maintaining normal blood flow to promote proper
      oxygen exchange, ensuring proper ventilation, and avoiding variations in
      temperature. Close collaboration between the anesthetist, the surgeon, and the
      neurophysiologist will ensure the success of intraoperative monitoring and make
      it possible to avoid neural injury by making timely changes in the surgical
      approach.

PMID- 17518175
TI  - [Two cases of early postoperative massive pulmonary thromboembolism after gastric
      bypass surgery].
AB  - Pulmonary thromboembolism in the early postoperative period is rare. We present 2
      cases of massive embolism that occurred soon after gastric bypass surgery. The
      first patient was a 32-year-old man, a smoker with a body mass index (BMI) of 52
      kg/m2, obstructive sleep apnea-hypopnea syndrome and venous insufficiency in the
      lower extremities. Fatal cardiorespiratory arrest occurred 22 hours after
      surgery. Autopsy confirmed massive pulmonary thromboembolism. The second patient
      was a 48-year-old woman with a BMI of 40 kg/m2 who had undergone abdominal
      hysterectomy 2 months earlier. She survived cardiorespiratory arrest occurring 11
      hours after surgery. There were no sequelae. The diagnosis of pulmonary
      thromboembolism was confirmed by transesophageal echocardiography. These patients
      undoubtedly had asymptomatic deep vein thrombosis before the operations.
      Prevention of pulmonary embolism is essential in high risk patients. The
      prophylactic measures usually applied are administration of low molecular weight
      heparin to prevent thrombosis, early ambulation, and the use of elastic
      compression stockings or intermittent pneumatic compression.

PMID- 17518176
TI  - [Conservative management of the airway following iatrogenic tracheal rupture].
AB  - The trachea of a 39-year-old man ruptured following intubation for fiberoptic
      bronchoscopy; the complication became evident during surgery as extensive
      subcutaneous emphysema developed. The emphysema resolved with conservative
      treatment. Tracheobronchial lesions are generally caused by direct trauma to the
      chest. Tracheal rupture due to intubation maneuvers is one of the complications
      anesthetists fear most. Although infrequent, such lesions are potentially fatal.
      Signs and symptoms can vary widely, from self-limiting asymptomatic subcutaneous
      emphysema immediately following surgery to severe complications such as tension
      pneumothorax, acute respiratory failure, pneumomediastinum, or even
      pneumopericardium. The absence of complications in patients treated
      conservatively has increased interest in using this approach to management when
      conditions are favorable, always with fiberoptic assessment to evaluate whether
      the lesion has resolved completely and without sequelae.

PMID- 17518177
TI  - [Perianesthetic complications in a woman with undiagnosed osteomalacia secondary
      to earlier gastric bypass surgery].

PMID- 17518178
TI  - [Anesthesia for laparoscopic adrenalectomy in a pregnant patient with Cushing
      syndrome].

PMID- 17518179
TI  - [Obstetric analgesia for a women with type III hereditary angioneurotic edema].

PMID- 17518180
TI  - [Difficult removal of a central venous catheter].

PMID- 17518181
TI  - [Managing anesthesia for a woman with Donohue syndrome].

PMID- 17518182
TI  - [Anesthesia for a boy with Rubinstein-Taybi syndrome].

PMID- 17518183
TI  - [Continuous positive airway pressure with a helmet during sedation for
      vertebroplasty in a patient with severe pulmonary emphysema].

PMID- 17518184
TI  - [Final leaf in the history of Spanish doctoral theses and treatises on
      anesthesia].

PMID- 17518185
TI  - [Anesthesia for a patient with blue rubber bleb nevus syndrome].

PMID- 17518186
TI  - [Anesthetic management during treatment of neonatal tracheoesophageal fistula].

PMID- 17518187
TI  - Making patients' lives comfortable?

PMID- 17518188
TI  - 'The pain makes you wish you were dead'.

PMID- 17518189
TI  - Hungry to be heard.

PMID- 17518190
TI  - Pass the parcel?

PMID- 17518191
TI  - A world of difference.

PMID- 17518192
TI  - Helping people at home.

PMID- 17518193
TI  - Subcutaneous infusion.

PMID- 17518194
TI  - Dignity in hospital.

PMID- 17518195
TI  - Community matrons: person-centred care planning (part one).
AB  - A total of 15 million people in England live with a long term condition. The
      government wants to improve the health and social care outcomes for the most
      vulnerable by offering them pro-active support and case management from community
      matrons. Personalised care planning is fundamental to the success of this
      intervention. Yet new role developments in nursing have often lacked rigorous
      evaluation, particularly in relation to clinical and service outcomes and patient
      perspectives. This article introduces a framework for person-centred care
      planning (McCormack and McCance 2006). It helps identify what community matrons
      are likely to need, do and think about in order to deliver truly person-centred
      care.

PMID- 17518196
TI  - Involving older people in improving general hospital care.
AB  - User involvement is high on the NHS agenda. At King's College Hospital, London,
      older people helped to develop the Improving Hospital Care for Older People
      project by producing teaching and learning materials for staff using e-learning.
      The project was set up by holding focus groups with older people. Staff surveys
      were also conducted to explore views and identify issues to be addressed. Older
      people's representatives were selected and directly involved in developing
      learning materials. This article describes the process of working together and
      includes the personal reflections of some of the key players. It discusses
      barriers to effective user involvement work between staff and older people, and
      identifies some benefits and opportunities presented by this approach.

PMID- 17518197
TI  - Improving mental health care in general hospitals.
AB  - The mental health needs of older people being cared for within general hospitals
      and other acute healthcare settings has been specifically identified as a
      priority for improvement. Yet in reality little has changed. The Department of
      Health (DH) (2006) has highlighted how many challenges still exist in developing
      effective integrated care for this patient group and continues to respond with
      further centrally initiated policy documents. This article explores the
      relationship between policy and practice and highlights how, despite their
      importance, policy initiatives alone are unlikely to be enough to ensure the
      effective delivery of mental health care for older people in general hospitals.

PMID- 17518198
TI  - Amanda phelan.

PMID- 17518199
TI  - Government plays the numbers game.

PMID- 17518200
TI  - 'Nursing teams are floundering because they lack supervision and direction'.

PMID- 17518201
TI  - Lost in transition.

PMID- 17518203
TI  - Improving services for gay and transgender patients.

PMID- 17518202
TI  - Getting to grips with the smoking bans.

PMID- 17518204
TI  - Blood pressure measurement. Part 2: Using automated devices.

PMID- 17518205
TI  - Compliance with guidelines on effective hand hygiene.
AB  - This article outlines in detail the processes involved in effective hand hygiene,
      as well as the responsibilities of nurses in relation to hand hygiene as a method
      of maintaining a safe environment for patients and staff. It also makes some
      recommendations to improve hand hygiene and reduce risk.

PMID- 17518206
TI  - Providing coping mechanisms is an essential aspect of care.

PMID- 17518207
TI  - Implementing guidance on pelvic floor exercises.
AB  - The NICE (2006) guidelines on female urinary incontinence suggest that pelvic
      floor muscle rehabilitation is an important component of treatment for managing
      stress and mixed urinary incontinence. Ian Pomfret and Clare Holden outline why
      implementing the recommendations requires specifically trained multiprofessional
      continence teams. They also highlight problems with implementing the
      recommendation that women should have a digital examination of the pelvic floor
      to assess muscle contraction.

PMID- 17518208
TI  - A guide to managing constipation: Part two.
AB  - In the first article in this three-part series, Gaye Kyle discussed the causes
      and assessment of constipation. This second article discusses the management of
      the condition.

PMID- 17518209
TI  - Assessing continence with bladder ultrasound.
AB  - Ray Addison outlines the principal uses of portable bladder ultrasound and
      reminds readers of the importance of reviewing the results of this investigation
      with other clinical investigations and the patient's health status.

PMID- 17518210
TI  - Coping with continence problems at work.
AB  - Debra Evans reports the results of explanatory research that explored the impact
      of continence problems on the ability to work.

PMID- 17518211
TI  - 'Are we really being as creative as we can be'?

PMID- 17518212
TI  - Cognitive functioning in children with and without Attention
      deficit/Hyperactivity Disorder with and without comorbid learning disabilities.
AB  - This study attempted to determine whether children with the combined subtype of
      attention-deficit/hyperactivity disorder (ADHD) have impairments in cognitive
      functioning and motor skills. The specific effect of the comorbidity of learning
      disabilities (LD) was also investigated. A battery of cognitive tests was
      administered to 26 children with a clinical diagnosis of ADHD-combined subtype
      (ADHD/C), to 24 children with ADHD/C with a comorbid diagnosis of LD (ADHD/C+LD),
      and to 102 participants without disabilities, all between ages 7 and 10. The
      testing battery consisted of tasks assessing memory, visuospatial and verbal
      abilities, and fine motor skills. In general, the test results of children with
      ADHD/C were poorer than those of the control group but better than the results of
      children with a combined ADHD/C+LD diagnosis (with the exception of motor
      skills). The predictive accuracy of the testing battery tasks in children with
      ADHD/C and ADHD/C+LD was examined. The results of a standard procedure of
      discriminant function analyses revealed that the measures correctly classified
      73.6% of the children.

PMID- 17518213
TI  - Efficacy of an intervention to improve fluency in children with developmental
      dyslexia in a regular orthography.
AB  - The purpose of this study was to examine the efficacy of a method to improve
      reading fluency in children with dyslexia. The method, which we named
      "subsyllabic," was aimed at automatizing the recognition of syllables within
      words in connected texts, presented by ad hoc software. Two versions of this
      method--one self-paced and the other one with automatic syllable identification
      were compared to a method based on phonemic awareness, assisted reading, and
      other psycholinguistic exercises. The efficacy of the two versions of the
      subsyllabic method was further studied by repeating the first version twice and
      the second version three times using an AB design, with each phase lasting
      approximately 3 months. This part of the study provided not only follow-up data
      but also useful information on if and how fluency may change after repeated
      treatment. Outcomes obtained by a total of 63 children with dyslexia suggested
      that the subsyllabic method was superior to the control method and that the use
      of an automatic presentation of target syllables produced better results.
      Furthermore, we observed that fluency improved approximately at the same rate
      after each treatment repetition. Our data support the possibility of improving
      reading fluency at a significant clinical level, at least for regular
      orthographies. The crucial component of the subsyllabic method seems to be the
      facilitation of syllable recognition within words in connected texts and the
      emphasis on their rapid recognition using an automatized procedure.

PMID- 17518214
TI  - Improving comprehension of expository text in students with LD: a research
      synthesis.
AB  - This article summarizes the findings of research studies designed to improve the
      comprehension of expository text for students with learning disabilities. Twenty
      nine studies were located that met the inclusion criteria. Interventions gleaned
      from the review were categorized as content enhancement (i.e., advance and
      graphic organizers, visual displays, mnemonic illustrations, and computer
      assisted instruction) or cognitive strategy instruction (i.e., text structure,
      main idea identification, summarization, questioning, cognitive mapping,
      reciprocal teaching). Treatment outcomes are discussed in relation to the various
      instructional approaches, student characteristics (e.g., grade, IQ),
      instructional features (e.g., materials, treatment length), methodological
      features, strategy maintenance, and generalization components. Implications for
      classroom practice and future research directions are provided.

PMID- 17518215
TI  - Speaking up for vocabulary: reading skill differences in young adults.
AB  - This study is part of a broader project aimed at developing cognitive and
      neurocognitive profiles of adolescent and young adult readers whose educational
      and occupational prospects are constrained by their limited literacy skills. We
      explore the relationships among reading-related abilities in participants ages 16
      to 24 years spanning a wide range of reading ability. Two specific questions are
      addressed: (a) Does the simple view of reading capture all nonrandom variation in
      reading comprehension? (b) Does orally assessed vocabulary knowledge account for
      variance in reading comprehension, as predicted by the lexical quality
      hypothesis? A comprehensive battery of cognitive and educational tests was
      employed to assess phonological awareness, decoding, verbal working memory,
      listening comprehension, reading comprehension, word knowledge, and experience
      with print. In this heterogeneous sample, decoding ability clearly played an
      important role in reading comprehension. The simple view of reading gave a
      reasonable fit to the data, although it did not capture all of the reliable
      variance in reading comprehension as predicted. Orally assessed vocabulary
      knowledge captured unique variance in reading comprehension even after listening
      comprehension and decoding skill were accounted for. We explore how a specific
      connectionist model of lexical representation and lexical access can account for
      these findings.

PMID- 17518216
TI  - Expressive writing difficulties in children described as exhibiting ADHD
      symptoms.
AB  - Three groups of children of different ages who were considered by their teachers
      as showing symptoms of attention-deficit/hyperactivity disorder (ADHD) and
      matched controls were tested in a series of expressive writing tasks, derived
      from a standardized writing test. In the first study, 24 sixth- and seventh-grade
      children with ADHD symptoms wrote a description of an image. The ADHD group's
      expressive writing was worse than that of the control group and associated with a
      higher number of errors, mainly concerning accents and geminates. The second
      study showed the generality of the effect by testing younger groups of children
      with ADHD symptoms and controls with another description task where a verbal
      description was substituted for the picture stimulus. The third study extended
      the previous observations with another type of writing task, the request of
      writing a narrative text. In all the three studies, children with ADHD symptoms
      scored lower than controls on four qualitative parameters (adequacy, structure,
      grammar, and lexicon), produced shorter texts, and made more errors. These
      studies show that children with ADHD symptoms have school difficulties also in
      writing-both in spelling and expression-and that these difficulties are extended
      to different tasks and ages.

PMID- 17518217
TI  - Foreign language learning difficulties in Italian children: are they associated
      with other learning difficulties?
AB  - A group of seventh- and eighth-grade Italian students with low achievement (LA)
      in learning English as a foreign language (FL) was selected and compared to a
      group with high achievement (HA) in FL learning. The two groups were matched for
      age and nonverbal intelligence. Two experiments were conducted to examine the
      participants' verbal and nonverbal learning skills, such as native language
      reading accuracy, speed and comprehension, calculation, and attention and self
      regulation. Both experiments showed that the LA group seemed at risk for reading
      comprehension difficulties, but its reading speed and accuracy were within the
      average range according to Italian norms. The results also excluded the
      possibility that FL learning difficulties of LA participants could be associated
      with a deficit in calculation. Furthermore, according to teachers' ratings,
      children with LA appeared at risk for attention-deficit disorder (ADD). The
      pattern of learning difficulties of seventh- and eighth-grade participants with
      LA appeared to be not completely comparable with that of high school students at
      risk of FL learning difficulties as described in the literature.

PMID- 17518218
TI  - Is there a common linkage among reading comprehension, visual attention, and
      magnocellular processing?
AB  - The authors examined the relationships between reading comprehension, visual
      attention, and magnocellular processing in 42 Grade 7 students. The goal was to
      quantify the sensitivity of visual attention and magnocellular visual processing
      as concomitants of poor reading comprehension in the absence of either vision
      therapy or cognitive intervention. Nineteen good readers (M = grade equivalent of
      11.2) and 23 poor readers (M = grade equivalent of 3.5) were identified.
      Participants were tested for visual attention skills (Cognitive Assessment
      System: CAS) and magnocellular integrity (Coherent Motion Threshold: CM).
      Individual and combined correlations of dependent variables with reading were
      significant at the 0.01 level. When combined, the two tests (CAS + CM) accounted
      for 61% of the variance in reading comprehension. Logistic regression analysis
      measured sensitivity of the two diagnostic tests. Attention tests correctly
      classified 95.7% of poor readers, and coherent motion correctly classified 78.3%
      of poor readers. When the data were combined, 91.3% of poor readers were
      correctly classified. The research reinforces the notion that a common linkage
      exists between reading comprehension, visual attention, and magnocellular
      processing. Diagnostic test batteries for students who have been identified as
      reading disabled should include magnocellular and visual attention tests.
      Procedures to diagnose and ameliorate these disabilities are discussed.

PMID- 17518219
TI  - Real-time measurement of outdoor tobacco smoke particles.
AB  - The current lack of empirical data on outdoor tobacco smoke (OTS) levels impedes
      OTS exposure and risk assessments. We sought to measure peak and time-averaged
      OTS concentrations in common outdoor settings near smokers and to explore the
      determinants of time-varying OTS levels, including the effects of source
      proximity and wind. Using five types of real-time airborne particle monitoring
      devices, we obtained more than 8000 min worth of continuous monitoring data,
      during which there were measurable OTS levels. Measurement intervals ranged from
      2 sec to 1 min for the different instruments. We monitored OTS levels during 15
      on-site visits to 10 outdoor public places where active cigar and cigarette
      smokers were present, including parks, sidewalk cafes, and restaurant and pub
      patios. For three of the visits and during 4 additional days of monitoring
      outdoors and indoors at a private residence, we controlled smoking activity at
      precise distances from monitored positions. The overall average OTS respirable
      particle concentration for the surveys of public places during smoking was
      approximately 30 microg m(-3). OTS exhibited sharp spikes in particle mass
      concentration during smoking that sometimes exceeded 1000 microg m(-3) at
      distances within 0.5 m of the source. Some average concentrations over the
      duration of a cigarette and within 0.5 m exceeded 200 microg m(-3), with some
      average downwind levels exceeding 500 microg m(-3). OTS levels in a constant
      upwind direction from an active cigarette source were nearly zero. OTS levels
      also approached zero at distances greater than approximately 2 m from a single
      cigarette. During periods of active smoking, peak and average OTS levels near
      smokers rivaled indoor tobacco smoke concentrations. However, OTS levels dropped
      almost instantly after smoking activity ceased. Based on our results, it is
      possible for OTS to present a nuisance or hazard under certain conditions of wind
      and smoker proximity.

PMID- 17518220
TI  - A fuzzy composting process model.
AB  - Composting processes are normally complicated with a variety of uncertainties
      arising from incomplete or imprecise information obtained in real-world systems.
      Previously, there has been a lack of studies that focused on developing effective
      approaches to incorporate such uncertainties within composting process models. To
      fill this gap, a fuzzy composting process model (FCPM) for simulating composting
      process under uncertainty was developed. This model was mainly based on
      integration of a fractional fuzzy vertex method and a comprehensive composting
      model. Degrees of influence by projected uncertain factors were also examined.
      Two scenarios were investigated in applying the FCPM method. In the first
      scenario, model simulation under deterministic conditions was conducted. A pilot
      scale experiment was provided for verifications. The result indicated that the
      proposed composting model could provide an excellent vehicle for demonstrating
      the complex interactions that occurred in the composting process. In the second
      scenario, application of the proposed FCPM was conducted under uncertainties. Six
      input parameters were considered to be of uncertain features that were reflected
      as fuzzy membership functions. The results indicated that the uncertainties
      projected in input parameters will result in significant derivations on system
      predictions; the proposed FCPM can generate satisfactory system outputs, with
      less computational efforts being required. Analyses on degree of influence of
      system inputs were also provided to describe the impacts of uncertainties on
      system responses. Thus, suitable measures can be adopted either to reduce system
      uncertainty by well-directed reduction of uncertainties of those high-influencing
      parameters or to reduce the computational requirement by neglecting those
      negligible factors.

PMID- 17518221
TI  - Particulate emissions from U.S. Department of Defense artillery backblast
      testing.
AB  - There is a dearth of information on dust emissions from sources that are unique
      to the U.S. Department of Defense testing and training activities. However,
      accurate emissions factors are needed for these sources so that military
      installations can prepare accurate particulate matter (PM) emission inventories.
      One such source, coarse and fine PM (PM10 and PM2.5) emissions from artillery
      backblast testing on improved gun positions, was characterized at the Yuma
      Proving Ground near Yuma, AZ, in October 2005. Fugitive emissions are created by
      the shockwave from artillery pieces, which ejects dust from the surface on which
      the artillery is resting. Other contributions of PM can be attributed to the
      combustion of the propellants. For a 155-mm howitzer firing a range of propellant
      charges or zones, amounts of emitted PM10 ranged from -19 g of PM10 per firing
      event for a zone 1 charge to 92 g of PM10 per firing event for a zone 5. The
      corresponding rates for PM2.5 were approximately 9 g of PM2.5 and 49 g of PM2.5
      per firing. The average measured emission rates for PM1o and PM2.5 appear to
      scale with the zone charge value. The measurements show that the estimated annual
      contributions of PM10 (52.2 t) and PM2.5 (28.5 t) from artillery backblast are
      insignificant in the context of the 2002 U.S. Environment Protection Agency (EPA)
      PM emission inventory. Using national-level activity data for artillery fire, the
      most conservative estimate is that backblast would contribute the equivalent of 5
      x 10(-4) % and 1.6 x 10(-3)% of the annual total PM10 and PM2.5 fugitive dust
      contributions, respectively, based on 2002 EPA inventory data.

PMID- 17518222
TI  - Source apportionment of ambient total suspended particulates and coarse
      particulate matter in urban areas of Jiaozuo, China.
AB  - Approximately 750 total suspended particulates (TSPs) and coarse particulate
      matter (PM10) filter samples from six urban sites and a background site and >210
      source samples were collected in Jiaozuo City during January 2002 to April 2003.
      They were analyzed for mass and abundances of 25 chemical components. Seven
      contributive sources were identified, and their contributions to ambient TSP/PM10
      levels at the seven sites in three seasons (spring, summer, and winter days) and
      a "whole" year were estimated by a chemical mass balance (CMB) receptor model.
      The spatial TSP average was high in spring and winter days at a level of
      approximately 530 microg/m(3) and low in summer days at 456 microg/m(3); however,
      the spatial PMo0 average exhibited little variation at a level of approximately
      325 microg/m(3), and PM10-to-TSP ratios ranged from 0.58 to 0.81, which suggested
      heavy particulate matter pollution existing in the urban areas. Apportionment
      results indicated that geological material was the largest contributor to ambient
      TSP/PM10 concentrations, followed by dust emissions from construction activities,
      coal combustion, secondary aerosols, vehicle movement, and other industrial
      sources. In addition, paved road dust and re-entrained dust were also apportioned
      to the seven source types and found soil, coal combustion, and construction dust
      to be the major contributors.

PMID- 17518223
TI  - Methyl bromide as a building disinfectant: interaction with indoor materials and
      resulting byproduct formation.
AB  - Several buildings were contaminated with Bacillus anthracis in the fall of 2001.
      These events required consideration of how to disinfect large indoor spaces for
      continued worker occupation. The interactions of gaseous disinfectants with
      indoor materials may inhibit the disinfection process, cause persistence of the
      disinfectant, and lead to possible byproduct formation and persistence. Methyl
      bromide (CH3Br) is a candidate for disinfection/deactivation of biological agents
      in buildings. In this study, 24 indoor materials were exposed to CH3Br for 16 hr
      at concentrations ranging from 100 to 2500 ppm in 48-L electropolished stainless
      steel chambers. CH3Br concentrations were measured during and after disinfection.
      Its interactions with materials were observed to be small, with nearly complete
      and rapid desorption. Between 3% and 8% of CH3Br adsorbed to four materials
      (office partition, ceiling tile, particle-board, and gypsum wallboard with satin
      paint), and the degree of adsorption decreased with increasing relative humidity.
      The percentage of adsorption to all other materials was <2%. This result suggests
      that when designing disinfection events with CH3Br, loss to indoor materials can
      be neglected in terms of disinfectant dose calculations. Possible reaction
      products were identified and/or quantified before and after exposure to CH3Br.
      Several monomethylated and dimethylated aliphatic compounds were observed in
      chamber air at low concentrations after the exposures of six materials to CH3Br.
      Concentration increases also occurred for chemicals that were observed to
      naturally off-gas from materials before exposure to CH3Br, suggesting that CH3Br
      may play a role in enhancing the natural off-gassing of chemicals, for example,
      by competitive displacement of compounds that already existed in the materials.
      The results described in this paper should facilitate the design of building
      disinfection systems involving CH3Br.

PMID- 17518224
TI  - Using prognostic model-generated meteorological output in the AERMOD dispersion
      model: an illustrative application in Philadelphia, PA.
AB  - In this study, we introduce the prospect of using prognostic model-generated
      meteorological output as input to steady-state dispersion models by identifying
      possible advantages and disadvantages and by presenting a comparative analysis.
      Because output from prognostic meteorological models is now routinely available
      and is used for Eulerian and Lagrangian air quality modeling applications, we
      explore the possibility of using such data in lieu of traditional National
      Weather Service (NWS) data for dispersion models. We apply these data in an urban
      application where comparisons can be made between the two meteorological input
      data types. Using the U.S. Environment Protection Agency's American
      Meteorological Society/U.S. Environmental Protection Agency Regulatory Model
      (AERMOD) air quality dispersion model, hourly and annual average concentrations
      of benzene are estimated for the Philadelphia, PA, area using both hourly MM5
      model-generated meteorological output and meteorological data taken from the NWS
      site at the Philadelphia International Airport. Our intent is to stimulate a
      discussion of the relevant issues and inspire future work that examines many of
      the questions raised in this paper.

PMID- 17518225
TI  - Investigation of a systematic offset in the measurement of organic carbon with a
      semicontinuous analyzer.
AB  - Organic carbon (OC) was measured semicontinuously in laboratory experiments of
      steady-state secondary organic aerosol formed by hydrocarbon + nitrogen oxide
      irradiations. Examination of the mass of carbon measured on the filter for
      various sample volumes reveals a systematic offset that is not observed when
      performing an instrumental blank. These findings suggest that simple subtraction
      of instrumental blanks determined as the standard analysis without sample
      collection (i.e., by cycling the pump and valves yet filtering zero liters of air
      followed by routine chemical analysis) from measured concentrations may be
      inadequate. This may be especially true for samples collected through the
      filtration of small air volumes wherein the influence of the systematic offset is
      greatest. All of the experiments show that filtering a larger volume of air
      minimizes the influence of contributions from the systematic offset. Application
      of these results to measurements of ambient concentrations of carbonaceous
      aerosol suggests a need for collection of sufficient carbon mass to minimize the
      relative influence of the offset signal.

PMID- 17518226
TI  - TiO2 nanotube-supported cu as the catalyst for selective NO reduction with NH3.
AB  - Catalyst supports composed of titanate nanotubes were prepared from hydrothermal
      treatment on TiO2 nanoparticles in NaOH followed by HCl washing. The nanotubes
      exhibited well-defined TiO2 anatase phase after calcination at 400 degrees C. The
      nanotube aggregates and other commercially available TiO2 nanoparticles, all with
      surface areas >300 m(2)/g, were impregnated with Cu and examined in selective
      catalytic reduction of NO with NH3. In catalyst preparation, the nanotubes were
      found to be more thermally stable than nanoparticles, withstanding agglomeration
      at elevated temperatures. The Cu species supported on the nanotubes showed a
      higher catalytic activity than those supported on the nanoparticles. Analysis
      with temperature programmed reduction, X-ray photoelectron spectroscopy, and NO
      adsorption reflected that the layered-titanate feature of the tube wall was
      advantageous for even distribution of the Cu species, thus leading to the high
      catalytic activity of the tubular Cu/TiO2 catalyst.

PMID- 17518227
TI  - Analysis and apportionment of organic carbon and fine particulate matter sources
      at multiple sites in the midwestern United States.
AB  - Speciated fine particulate matter (PM2.5) data collected as part of the
      Speciation Trends Network at four sites in the Midwest (Detroit, MI; Cincinnati,
      OH; Indianapolis, IN; and Northbrook, IL) and as part of the Interagency
      Monitoring of Protected Visual Environments program at the rural Bondville, IL,
      site were analyzed to understand sources contributing to organic carbon (OC) and
      PM2.5 mass. Positive matrix factorization (PMF) was applied to available data
      collected from January 2002 through March 2005, and seven to nine factors were
      identified at each site. Common factors at all of the sites included mobile
      (gasoline)/secondary organic aerosols with high OC, diesel with a high elemental
      carbon/OC ratio (only at the urban sites), secondary sulfate, secondary nitrate,
      soil, and biomass burning. Identified industrial factors included copper smelting
      (Northbrook, Indianapolis, and Bondville), steel/manufacturing with iron
      (Northbrook), industrial zinc (Northbrook, Cincinnati, Indianapolis, and
      Detroit), metal plating with chromium and nickel (Detroit, Indianapolis, and
      Bondville), mixed industrial with copper and iron (Cincinnati), and limestone
      with calcium and iron (Bondville). PMF results, on average, accounted for 96% of
      the measured PM2.5 mass at each site; residuals were consistently within
      tolerance (+/-3), and goodness-of-fit (Q) was acceptable. Potential source
      contribution function analysis helped identify regional and local impacts of the
      identified source types. Secondary sulfate and soil factors showed regional
      characteristics at each site, whereas industrial sources typically appeared to be
      locally influenced. These regional factors contributed approximately one third of
      the total PM2.5 mass, on average, whereas local mobile and industrial sources
      contributed to the remaining mass. Mobile sources were a major contributor (55
      76% at the urban sites) to OC mass, generally with at least twice as much mass
      from nondiesel sources as from diesel. Regional OC associated with secondary
      sulfate and soil was generally low.

PMID- 17518228
TI  - Fine and coarse particulate matter chemical characterization in a heavily
      industrialized city in central Mexico during Winter 2003.
AB  - This paper presents the results of the first reported study on fine particulate
      matter (PM) chemical composition at Salamanca, a highly industrialized urban area
      of Central Mexico. Samples were collected at six sites within the urban area
      during February and March 2003. Several trace elements, organic carbon (OC),
      elemental carbon (EC), and six ions were analyzed to characterize aerosols.
      Average concentrations of PM with aerodynamic diameter of less than 10 microm
      (PM10) and fine PM with aerodynamic diameter of less than 2.5 microm (PM2.5)
      ranged from 32.2 to 76.6 [g m(-3) and 11.1 to 23.7 microg m(-3), respectively. OC
      (34%), SO4= (25.1%), EC (12.9%), and geological material (12.5%) were the major
      components of PM2.5. For PM10 geological material (57.9%), OC (17.3%), and SO4=
      (9.7%) were the major components. Coarse fraction (PM,, -PM2.5), geological
      material (81.7%), and OC (8.6%) were the dominant species, which amounted to
      90.4%. Correlation analysis showed that sulfate in PM2.5 was present as ammonium
      sulfate. Sulfate showed a significant spatial variation with higher
      concentrations to the north resulting from predominantly southwesterly winds
      above the surface layer and by major SO2 sources that include a power plant and
      refinery. At the urban site of Cruz Roja it was observed that PM2.5 mass
      concentrations were similar to the submicron fraction concentrations.
      Furthermore, the correlation between EC in PM2.5 and EC measured from an
      aethalometer was r(2) = 0.710. Temporal variations of SO2 and nitrogen oxide were
      observed during a day when the maximum concentration of PM2.5 was measured, which
      was associated with emissions from the nearby refinery and power plant. From
      cascade impactor measurements, the three measured modes of airborne particles
      corresponded with diameters of 0.32, 1.8, and 5.6 microm.

PMID- 17518229
TI  - Standardizing dictated documents. New standards are beginning to be cast on the
      electronic medical record scene.

PMID- 17518230
TI  - Vision of tomorrow. Accenture's Online Health Services prototype looks to give
      vendors an idea of what may be possible.

PMID- 17518231
TI  - Stamp of approval. EHNAC announces its first certified e-prescribing network.

PMID- 17518232
TI  - State alliance on track. A new national panel gets the green light for exploring
      a variety of e-health issues, including licensure, liability and privacy.

PMID- 17518233
TI  - Performance improvement: EMR nirvana. Part I: the landscape.

PMID- 17518234
TI  - Hospitals take action to help patients. Part II: the improvements.

PMID- 17518235
TI  - Organizations sign up and climb on board. Part III: connecting the docs.

PMID- 17518236
TI  - Show me the system. Tips on choosing an EHR and PM system that really works.

PMID- 17518237
TI  - Team EMR. How to maximize productivity and potential for both the individual and
      the team.

PMID- 17518238
TI  - The adoption hurdle. External influences continue to impact physician EHR
      adoption.

PMID- 17518239
TI  - Uncovering the truth. Debunking 10 myths about why community hospitals shouldn't
      adopt EHRs.

PMID- 17518240
TI  - The 360-degree approach. EHRs are only a first step in what should be an effort
      to integrate clinical and financial applications.

PMID- 17518241
TI  - The little guy. What electronic health records look like at a small practice.

PMID- 17518242
TI  - Hospital, unplugged. Nick Christinao warns that when spending on wireless
      infrastructure, paying now is better than paying later.

PMID- 17518243
TI  - Wag the dog. Is your IT department running the business operations or is your
      business operations running the IT?

PMID- 17518244
TI  - Surfing the web. Searching the Internet can yield best practices and clinical
      guidelines for healthcare providers.

PMID- 17518245
TI  - Use and abuse. Adopting an electronic medical system is only the first step to
      delivering seamless care.

PMID- 17518246
TI  - Wound healing process of a full-thickness skin wound model in rats.
AB  - Using a rat full-thickness skin wound model, confocal laser scanning microscopy
      was carried out for examination of angiogenesis in granulation tissue formation.
      By semi-quantitation analysis with reverse transcription-polymerase chain
      reaction (RT-PCR), assessment was made of mRNA expression in the vascular
      endothelial growth factor (VEGF) and connective tissue growth factor (CTGF).
      Immunohistological analysis was also made to determine the location of these
      factors in granulation tissue at the protein level. Comparison was made of the
      cytokines in granulation and angiogenesis. Chronic granulation tissue with
      advanced fibrosis could be clearly demonstrated by the inhibition of wound
      contraction and epithelialization. From the results of the present study, VEGF
      would appear quite closely involved in angiogenesis in granulation tissue
      formation and pericytes may possibly give rise to VEGF and have significant roles
      in angiogenesis even with inhibition of epithelialization. CTGF expression in
      parenchyma is considerable during granulation and thus possibly may be related to
      the progress of fibrosis.

PMID- 17518247
TI  - Whole stomach transposition without gastric drainage procedure: a good surgical
      option to restore digestive continuity after esophagectomy.
AB  - After esophagectomy, the stomach is usually used to restore digestive continuity.
      To prevent postoperative delayed gastric emptying, most authors perform a gastric
      drainage procedure or transpose a tubulized stomach. The aim of our work is to
      evaluate the emptying of a transposed whole stomach without performing a
      pyloromyotomy or a pyloroplasty. From 1996 to January 2004, 45 patients underwent
      total esophagectomy for cancer or for caustic stenosis. Reconstruction of
      digestive continuity was realized through transposition of the whole stomach
      without performing a pyloric drainage procedure. At 12 months after the
      intervention, 35 patients (77.8%; 20 men and 15 women) were submitted to a
      gastric emptying scintigraphic study by means of ingestion of a mixed meal
      labeled with 37 MBq 99mTc-sulfur colloid. Mean half-emptying time was 71.4
      minutes (range, 15-90 minutes; reference range, 83 +/- 34 minutes): all the
      patients were in the normal range except one. No patient complained of delayed
      gastric emptying symptoms. After esophagectomy, the transposition of the whole
      stomach without a pyloric drainage procedure seems to be an interesting option,
      and is not associated with delayed gastric emptying.

PMID- 17518248
TI  - Iliac vessel injury by a cement spacer: report of a case.
AB  - The use of antibiotic-impregnated acrylic cement as a bone spacer between the
      intervals of revision hip arthroplasty for infection has been widely practiced.
      Vascular injuries caused by the migration of a cement spacer with subsequent
      erosion of the vessel wall have never been reported. A 67-year-old woman
      presented with tense swelling over her left lower extremity and hemarthroses of
      the left hip after implantation of a cement spacer for infected hip arthroplasty.
      Complete external compression of the external iliac vein and laceration of the
      iliac artery by the spacer were found. The symptoms were resolved after surgical
      debridement, removal of the spacer and femoral stem, and repair of the vessel.
      Cautious placement of a cement spacer in the acetabular fossa accompanied with
      poor bone stock must be emphasized.

PMID- 17518249
TI  - Novel treatment of intractable rectal strictures associated with anastomotic
      leakage using a stenosis-cutting device.
AB  - Disruption of an anastomosis after a low anterior resection reconstructed by a
      double stapling technique is a relatively rare complication but leads to a severe
      anastomotic stricture. Furthermore, this type of stricture is usually resistant
      to conventional treatment. A previously developed type of staple cutter (STENO
      CUTTER) was applied in order to evaluate the clinical effects for the treatment
      of severe rectal stricture associated with anastomotic leakage. The incidence of
      leakage was 11 out of 371 patients (3.0%). The incidence of subsequent stricture
      in the leakage group (54.5%) was significantly higher than that in the nonleakage
      group (6.7%; P < 0.0001). Six out of 11 patients with leakage had anastomotic
      stricture with the distressing symptoms of frequent bowel movements and ileus.
      Excellent dilation was performed in all of the six strictures using the STENO
      CUTTER. Because of the excellent efficacy, in addition to safe and easy use, this
      treatment is highly recommended for stricture of the rectum associated with
      anastomotic leakage.

PMID- 17518250
TI  - Simultaneous bilateral anterior fracture dislocation of the shoulder with
      neurovascular injury: report of a case.
AB  - This paper reports an unusual case of orthopedic trauma in a 29-year-old man who
      experienced concomitant bilateral anterior shoulder fracture dislocation with
      associated brachial plexus and axillary artery injury. We also highlight the
      mechanism underlying this rare workplace injury related to use of a forklift.

PMID- 17518251
TI  - Clinical pathway after lung transplantation shortens hospital length of stay
      without affecting outcome.
AB  - Transplant programs are under pressure to resolve multiple challenges related to
      quality, cost, and access in a resource-driven customer-focused health care
      environment. We reviewed outcomes of patients undergoing isolated lung
      transplantation using a single postoperative clinical pathway, developed between
      the specialties of Thoracic Surgery, Pulmonary and Critical Care Medicine, and
      Nursing. The data were retrospectively reviewed for mortality, length to
      extubation (LE), hospital length of stay (LOS), and readmissions of 183
      consecutive patients. One hundred ten women and 73 men with a mean age of 48 +/-
      12 years underwent 90 bilateral, 88 single, and 6 repeat lung transplantations.
      Median LE was 17 hours, and the LOS was 7 days. The operative mortality was 6.5%.
      One- and 3-year survivals were 82% and 73%, respectively. We conclude that a
      single multidisciplinary clinical pathway can facilitate early discharge from the
      hospital. Early hospital discharge after lung transplantation does not compromise
      early or late outcome.

PMID- 17518252
TI  - Shoulder restraint injury of the female breast.
AB  - Female breast trauma occasionally occurs while using a three-point lap-diagonal
      seat belt while involved in a motor vehicle collision. Breast trauma is either a
      crush injury or an avulsion injury. Breast traumatic injury is infrequently
      reported. The records and complete follow-up results from all patients who were
      treated for breast trauma caused by lap-diagonal seat belt injury over a 25-year
      period were reviewed and reported. A series of 19 female patients were treated
      for breast trauma that occurred during a motor vehicle collision in which the
      patient was using a three-point lap-diagonal seat belt restraint. Patient age
      range at the time of injury was 18-75 years. The patients' breast injuries were
      classified according to the type and severity of breast trauma. Fourteen patients
      had a class I mild crush injury. All recovered completely with conservative
      breast care. Four patients had a class II moderate crush injury. All four
      patients had an area of painful chronic fat necrosis removed. Two of four
      patients with a class II injury continue to have mild to moderate chronic breast
      pain. A single patient with a class III severe crush injury was successfully
      treated nonsurgically. The breast healed with a diagonal furrow. No chronic
      breast pain has been associated with this class III breast crush injury. No class
      IV avulsion breast injuries were treated in this clinical series. A
      classification of breast trauma from a motor vehicle collision in which the
      female was wearing a three-point lap-diagonal seat belt restraint has been
      developed. Results of treatment of 19 patients are reported with breast trauma,
      with a clinical guide for immediate and long-term care. Chronic breast pain
      persists in two patients in this series with a class II breast injury who had an
      area of traumatic fat necrosis. No breast cancer occurred in long-term complete
      follow-up in this series of 19 patients with breast trauma.

PMID- 17518253
TI  - Significance of platelet counts in patients who underwent surgical treatment for
      lung metastasis.
AB  - Many studies have asserted that thrombocytosis has a prognostic impact in various
      malignancies. To date, there has been no report of platelet value in patients
      with pulmonary metastasis. We retrospectively reviewed the medical charts of 143
      patients with resection for lung metastasis. The thrombocyte cut-off was 22 x
      10(4) /ml, which was the average count in this study, and we separated patients
      into two groups (high group versus low group). Cases of larger-size (>2-0.5 cm)
      pulmonary metastasis showed a significant increase compared with cases of smaller
      size (-2 cm; P = 0.0040). In univariate analysis, location in the bilateral lung
      and higher platelet count were significantly associated with prognosis.
      Multivariate analysis showed that only the high platelet group (P = 0.0334)
      showed significant independent prognostic factors. Platelet count may be a
      valuable marker in patients with pulmonary metastasis and for surgical indication
      with higher count.

PMID- 17518254
TI  - Expanded criteria for hepatocellular carcinoma and liver transplantation.
AB  - In this study, we evaluated our early results of liver transplantation for
      hepatocellular carcinoma. Between January 2003 and June 2006, 26 patients (4
      women and 22 men; age, 1.1-65 years) with preoperatively diagnosed or incidental
      hepatocellular carcinoma (HCC) underwent liver transplantation at our center.
      Inclusion criteria (independent of tumor size and number of tumor nodules) were
      no invasion of major vascular structure and no evidence of extrahepatic disease.
      In 13 of the patients, tumors were beyond the Milan criteria. At this writing,
      with a mean follow-up of 16.5 months (range, 1-31 months), all patients are doing
      well with excellent graft function. The longest survival is 2.5 years, and our
      patient survival rate is 100%. There has been only one tumor recurrence that was
      4 months after liver transplantation. Liver transplantation provides long patient
      and disease-free survival, even in patients with HCC that exceeds the Milan
      criteria.

PMID- 17518255
TI  - Can recurrent reflux disease after fundoplication be circumvented by adding a
      vagotomy?
AB  - Gastro-esophageal reflux disease (GORD) is caused by a weak lower esophageal
      sphincter. Open Nissen fundoplication has been the most common surgical treatment
      of GORD and hiatus hernia. This paper describes the symptomatic result and
      quantifies the endoscopic improvement achieved by open Nissen fundoplication
      alone and when combined with truncal vagotomy in a series of 21 cases and studies
      whether the added vagotomy confers any additional benefits. From the results, it
      was concluded that, compared with fundoplication alone, an additional vagotomy
      does seem to prevent recurrent reflux disease. Therefore, in the absence of any
      contraindication, it is strongly recommended to combine a vagotomy(and if
      necessary a drainage procedure) with a Nissen fundoplication for the surgical
      treatment of GORD and hiatus hernia.

PMID- 17518256
TI  - Inflammatory pseudotumor of the spleen: CT and MRI findings.
AB  - Inflammatory pseudotumors rarely occur in the spleen. We report such a case with
      characteristic computed tomography (CT) and magnetic resonance imaging (MRI)
      findings. A CT scan showed an isodense nodular mass with gradual mild enhancement
      on delayed-phase contrast-enhanced images. MRI showed a mass with isointense
      signal on T1-weighted images and hypointense signal on T2-weighted images. The
      tumor mass showed progressive inhomogeneous enhancement on gadolinium-enhanced
      images. The patient received splenectomy, and histologic diagnosis was compatible
      with inflammatory pseudotumor.

PMID- 17518257
TI  - How do you investigate complaints about staff or physicians?

PMID- 17518258
TI  - CMS announces proposed rule on physician fee schedule calculation method.

PMID- 17518259
TI  - Walking the talk on universal health insurance.

PMID- 17518260
TI  - What's ahead for medical practice? Meeting tomorrow's challenges.

PMID- 17518261
TI  - The digital lockbox. A virtual mail-processing assistant.

PMID- 17518262
TI  - Giving seniors a helping hand to health care. Case study: when Medicare rates cut
      seniors' access to care, one community found solutions.

PMID- 17518263
TI  - Boom or bust? How to attract and keep baby boomer patients.

PMID- 17518264
TI  - Real-time claims adjudication. . .can put money in a practice's pocket right
      away.

PMID- 17518265
TI  - Are you ready for disaster? Pandemic flu, monster hurricanes, bioterrorism--how
      to prepare your practice for the unthinkable.
AB  - Unthinkable disasters are no longer unthinkable. Yet almost half of medical group
      practices--43 percent--lack a formal emergency plan. If that doesn't get your
      attention, this might: 82 percent of surveyed medical group practices believe
      that emergency preparation is the administrator's job. Here's how to get started.

PMID- 17518266
TI  - Physician dispensing: an old idea is new again.
AB  - Faced with declining reimbursement for infusional therapies, an oncology practice
      turned to physician dispensing to offset the loss. Its leaders quickly discovered
      that the dispensing-vendor landscape was limited, and few guidelines existed for
      product line development. Yet the approach offers a competitive response to the
      changing health care landscape. With physician-dispensing prescription costs 50
      percent below the national average and generic substitution 50 percent higher
      than the national average, the potential cost savings for payers and consumers is
      staggering.

PMID- 17518267
TI  - Getting paid for taking ER calls: who decides, and how much is fair?
AB  - Most physicians have voluntarily taken calls at hospital emergency rooms because
      of medical staff bylaw requirements, a sense of professional or ethical
      obligation or civic commitment. Today, however, most specialists expect to
      receive some form of remuneration for taking ER calls. Physicians' desire for
      such a stipend obviously must coincide with a hospital's willingness to pay--and
      this leads to the key question of the fair market value, or reasonableness, of a
      specific compensation level.

PMID- 17518268
TI  - ECTO-NOX target for the anticancer isoflavene phenoxodiol.
AB  - Phenoxodiol, a synthetic isoflavene with clinical efficacy in the management of
      ovarian and other forms of human cancer, blocked the activity of a cancer
      specific and growth-related cell surface ECTO-NOX protein with both oxidative
      (hydroquinone) and protein disulfide-thiol interchange activity designated tNOX.
      Purified recombinant tNOX bound phenoxodiol with high affinity (Kd of 50 nM). The
      tNOX protein appeared to be both necessary and sufficient for the cancer-specific
      cytotoxicity of phenoxodiol. Growth inhibition of fibroblasts from embryos of
      mice expressing a tNOX transgene, but not from wild-type mice, was inhibited by
      phenoxodiol followed by apoptosis. Both the oxidative and protein disulfide-thiol
      interchange activities that alternate to generate the complex set of oscillations
      with a period length of 22 min (24 min for the constitutive counterpart CNOX)
      that characterize ECTO-NOX proteins respond to phenoxodiol. Oxidation of NADH or
      reduced coenzyme Q10 was rapidly blocked by phenoxodiol. In contrast, the protein
      disulfidethiol interchange activity measured either by the restoration of
      activity to scrambled and inactive RNase or from the cleavage of dithiodipyridine
      (EC50 of 50 nM) was inhibited progressively over an interval of 60 min that
      spanned three cycles of activity. Inhibition of the latter paralleled the
      inhibition of cell enlargement and the consequent inability of inhibited cells to
      initiate traverse of the cell cycle. Activities of constitutive ECTO-NOX (CNOX)
      forms of either cancer or noncancer cells were unaffected by phenoxodiol to help
      explain how the cytotoxic effects of phenoxodiol may be restricted to cancer
      cells.

PMID- 17518269
TI  - Antitumor effects of hydroxycamptothecin-loaded poly[ethylene glycol]-poly [gamma
      benzyl-L-glutamate] micelles against oral squamous cell carcinoma.
AB  - Therapeutic use of hydroxycamptothecin (HCPT), a promising antitumor agent, is
      limited by its poor solubility and rapid destruction. Amphiphilic block copolymer
      micelle carriers possess significant potential for improving drug solubility and
      stability. Poly[ethylene glycol]-poly[gamma-benzyl-L-glutamate] (PEG-PBLG)
      micelles were prepared and loaded with the active lactone form of HCPT using an
      uncomplicated dialysis method. HPLC and scanning electron microscopy studies
      revealed an encapsulation efficiency of 56.8% and a core-shell figure with a mean
      diameter of 200 nm. Encapsulated HCPT lactone was compared with the less active,
      open ring-carboxylated HCPT-Na+ soluble form generated in vivo from the free
      active lactone for activity against oral squamous cell carcinoma. Cytotoxicity in
      vitro was measured in cultured Tca8113 cells by the MTT assay and microscopy
      techniques. The golden hamster cheek pouch squamous cell carcinoma model was
      employed for in vivo studies; encapsulated lactone and open ring-carboxylated
      forms of HCPT were administered intraperitoneally, followed by determinations of
      tumor growth rate and inhibition ratio. PEG-PBLG micelles were not cytotoxic in
      vitro. At 48 h of treatment, open ring-carboxylated HCPT proved significantly
      more cytotoxic in vitro than encapsulated HCPT lactone. At 96 h, however, the
      open ring-carboxylated and encapsulated drugs displayed comparable in vitro
      cytotoxicities. In the in vivo squamous cell carcinoma model, encapsulated HCPT
      lactone produced greater and more prolonged tumor suppression compared to the
      open ring-carboxylated form. The antitumor effects of HCPT/PEG-PBLG micelles
      against oral squamous cell carcinoma in vivo are concluded to be superior to
      those exerted by open ring-carboxylated HCPT.

PMID- 17518270
TI  - DMBA/TPA-induced tumor formation is aggravated in human papillomavirus type 16
      E6/E7 transgenic mouse skin.
AB  - Human papillomavirus type 16 (HPV16) is a major causative factor in the
      development of uterine cervical carcinomas. We investigated the role of E6/E7 in
      tumor formation. Skin-specific E6/E7 transgenic mice showed approximately twice
      as many tumors compared with nontransgenic mice in dimethylbenz[a]anthracene
      (DMBA)-initiated and a 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two
      stage skin carcinogenesis. This model showed a significant increase of epidermal
      cell proliferation in the transgenic mice. The 8-hydroxy-2'deoxyguanosine (8OH
      dG) detection assay showed that oxidative DNA damage was significantly higher in
      the transgenic mice after TPA treatments. The overexpression of E6/E7 in the skin
      in the DMBA/TPA two-stage-induced carcinogenesis model aggravated the incidence
      of tumor formation. HPV16 E6/E7 appears to act as an enhancer of carcinogenesis
      that requires initiation by DMBA and promotion by TPA.

PMID- 17518271
TI  - Relationship between the loss of heterozygosity and tobacco smoking in pulmonary
      adenocarcinoma.
AB  - A loss of heterozygosity (LOH) is a major cause of lung carcinogenesis, and it is
      considered to be related to tobacco smoking in central type lung cancer. We
      investigated the relationship between LOH in lung adenocarcinoma and tobacco
      smoking. In a consecutive series of 50 patients with lung adenocarcinoma who
      underwent a surgical resection, cancer tissue specimens and corresponding normal
      peripheral lung and central bronchial tissue specimens were analyzed for LOH at
      the regions of D3S1234 (FHIT), D3S1300 (FHIT), D9S171 (CDKN2), and D17S796 (p53)
      by polymerase chain reaction using four fluorescence-labeled dinucleotide
      markers. To examine how cells are influenced by smoking, the A549 cell line was
      exposed to benzo[a]pyrene (B[a]P) for 24 weeks and then was subjected to the
      above analysis. The LOH in cancer tissue was thus detected in four (17%) patients
      at D3S1234, six (14%) at D3S1300, and seven (18%) at D17S796, but no LOH was
      detected in any normal tissue specimens. The incidence of LOHs in cancer tissue
      specimens from active smokers was 21% at D3S1234, 11% at D3S1300, and 19% at
      D17S796, whereas that of LOHs from nonactive smokers was 0% at D3S1234, 19% at
      D3S1300, and 14% at D17S796. Analyzing the relationship between the pack-year
      index and the presence of LOH, a significant difference was found among the
      active smokers. Besides, in the A549 cell line exposed to B[a]P, LOH was de novo
      detected in one (D2S123) of the nine regions examined. The incidence of LOH could
      be influenced by tobacco smoking in lung adenocarcinoma, thus suggesting the
      presence of an important event in the carcinogenesis of this disease.

PMID- 17518272
TI  - Combination therapy of personalized peptide vaccination and low-dose estramustine
      phosphate for metastatic hormone refractory prostate cancer patients: an analysis
      of prognostic factors in the treatment.
AB  - The aim of this study was to investigate prognostic factors of patients with
      metastatic hormone refractory prostate cancer (HRPC) under combined
      administration of personalized peptide vaccination and low-dose estramustine
      phosphate (EMP). From February 2001 to July 2004, 58 men with metastatic HRPC
      received the combination therapy of personalized peptide vaccination and low-dose
      EMP. Conducted immune monitorings for those patients were peptide-specific
      cytotoxic T lymphocyte (CTL) precursor analysis by interferon-gamma production
      and peptide-reactive immunoglobulin G (IgG) by an enzyme-linked immunosorbent
      assay. Clinical responses and survival times were also evaluated. The combination
      therapy was well tolerated with no major adverse effects. Increased levels of CTL
      precursors and IgG responses to the vaccinated peptides were observed in 29 of 37
      (78%) patients and in 36 of 41 (88%) patients tested, respectively. A prostate
      specific antigen decline of at least 50% occurred in 24% of patients. The median
      survival time was 17 months (95% confidence interval, 12-25 months). Cox
      proportional hazards analysis showed that a low number of lymphocytes (p =
      0.0075, odds ratio 2.700), a negative immunological activity response after the
      vaccination (p = 0.0185, odds ratio 2.658), and poor performance status (p =
      0.0347, odds ratio 2.569) were independent predictors of disease death. These
      encouraging results show the need for further evaluation of the combination of
      personalized peptide vaccination and low dose of EMP for metastatic HRPC
      patients.

PMID- 17518273
TI  - Feasibility of employing model-based optimization of pulse amplitude and
      electrode distance for effective tumor electropermeabilization.
AB  - In electrochemotherapy (ECT) electropermeabilization, parameters (pulse
      amplitude, electrode setup) need to be customized in order to expose the whole
      tumor to electric field intensities above permeabilizing threshold to achieve
      effective ECT. In this paper, we present a model-based optimization approach
      toward determination of optimal electropermeabilization parameters for effective
      ECT. The optimization is carried out by minimizing the difference between the
      permeabilization threshold and electric field intensities computed by finite
      element model in selected points of tumor. We examined the feasibility of model
      based optimization of electropermeabilization parameters on a model geometry
      generated from computer tomography images, representing brain tissue with tumor.
      Continuous parameter subject to optimization was pulse amplitude. The distance
      between electrode pairs was optimized as a discrete parameter. Optimization also
      considered the pulse generator constraints on voltage and current. During
      optimization the two constraints were reached preventing the exposure of the
      entire volume of the tumor to electric field intensities above permeabilizing
      threshold. However, despite the fact that with the particular needle array holder
      and pulse generator the entire volume of the tumor was not permeabilized, the
      maximal extent of permeabilization for the particular case (electrodes, tissue)
      was determined with the proposed approach. Model-based optimization approach
      could also be used for electro-gene transfer, where electric field intensities
      should be distributed between permeabilizing threshold and irreversible threshold
      the latter causing tissue necrosis. This can be obtained by adding constraints on
      maximum electric field intensity in optimization procedure.

PMID- 17518275
TI  - Extracting physiologically relevant parameters of vocal folds from high-speed
      video image series.
AB  - In this paper, a new method is proposed to extract the physiologically relevant
      parameters of the vocal fold mathematic model including masses, spring constants
      and damper constants from high-speed video (HSV) image series. This method uses a
      genetic algorithm to optimize the model parameters until the model and the
      realistic vocal folds have similar dynamic behavior. Numerical experiments
      theoretically test the validity of the proposed parameter estimation method. Then
      the validated method is applied to extract the physiologically relevant
      parameters from the glottal area series measured by HSV in an excised larynx
      model. With the estimated parameters, the vocal fold model accurately describes
      the vibration of the observed vocal folds. Further studies show that the proposed
      parameter estimation method can successfully detect the increase of longitudinal
      tension due to the vocal fold elongation from the glottal area signal. These
      results imply the potential clinical application of this method in inspecting the
      tissue properties of vocal fold.

PMID- 17518274
TI  - Are patient-specific joint and inertial parameters necessary for accurate inverse
      dynamics analyses of gait?
AB  - Variations in joint parameter (JP) values (axis positions and orientations in
      body segments) and inertial parameter (IP) values (segment masses, mass centers,
      and moments of inertia) as well as kinematic noise alter the results of inverse
      dynamics analyses of gait. Three-dimensional linkage models with joint
      constraints have been proposed as one way to minimize the effects of noisy
      kinematic data. Such models can also be used to perform gait optimizations to
      predict post-treatment function given pre-treatment gait data. This study
      evaluates whether accurate patient-specific JP and IP values are needed in three
      dimensional linkage models to produce accurate inverse dynamics results for gait.
      The study was performed in two stages. First, we used optimization analyses to
      evaluate whether patient-specific JP and IP values can be calibrated accurately
      from noisy kinematic data, and second, we used Monte Carlo analyses to evaluate
      how errors in JP and IP values affect inverse dynamics calculations. Both stages
      were performed using a dynamic, 27 degrees-of-freedom, full-body linkage model
      and synthetic (i.e., computer generated) gait data corresponding to a nominal
      experimental gait motion. In general, JP but not IP values could be found
      accurately from noisy kinematic data. Root-mean-square (RMS) errors were 3
      degrees and 4 mm for JP values and 1 kg, 22 mm, and 74 500 kg * mm2 for IP
      values. Furthermore, errors in JP but not IP values had a significant effect on
      calculated lower-extremity inverse dynamics joint torques. The worst RMS torque
      error averaged 4% bodyweight * height (BW * H) due to JP variations but less than
      0.25% (BW * H) due to IP variations. These results suggest that inverse dynamics
      analyses of gait utilizing linkage models with joint constraints should calibrate
      the model's JP values to obtain accurate joint torques.

PMID- 17518276
TI  - Predictive haemodynamics in a one-dimensional human carotid artery bifurcation.
      Part I: Application to stent design.
AB  - A diagnostic technique is proposed to identify patients with carotid stenosis who
      could most benefit from angioplasty followed by stent implantation. This
      methodology involves performing a parametric study to investigate the
      haemodynamic behavior due to alterations in the stenosis shapes in the internal
      carotid artery (ICA). A pulsatile 1-D Navier-Stokes solver incorporating fluid
      wall interactions for a Newtonian fluid which predicts pressure and flow in the
      human carotid artery bifurcation is used for the numerical simulations. In order
      to assess the performance of each individual geometry, we introduce pressure
      variation factor as a metric to directly compare the global effect of variations
      in the geometry. It is shown that the probability of an overall catastrophic
      effect is higher when the stenosis is present in the upstream segment of the ICA.
      Furthermore, maximum pressure is used to quantify the local effects of geometry
      changes. The location of the peak and extent of stenosis are found not to
      influence maximum pressure. We also show how these metrics respond after stent
      deployment into the stenosed part of the ICA. In particular, it is found that
      localized pressure peaks do not depend on the length of a stent. Finally, we
      demonstrate how these metrics may be applied to cost-effectively predict the
      benefit of stenting.

PMID- 17518277
TI  - How visual feedback of decomposed movements of the center of pressure
      trajectories affects undisturbed postural control of healthy individuals.
AB  - The center-of-pressure (CP) trajectory is a complex movement comprising both the
      vertically projected displacements of the centre-of-gravity (CG(v)) and the CP -
      CG(v) differences whose magnitudes are proportional to the horizontal
      accelerations communicated to the CG. One may, therefore, investigate whether the
      information given by these movements can be differentially used for controlling
      the standing posture. To this aim, a group of healthy adults was tested through
      four conditions including visual feedback (VFB) of their CP in real time and,
      with a 578 ms delay, CP, CG(v) and CP - CG(v) movements. The CG(v) and, thus, CP 
      C G, movements, were implemented from a numerical filter applied to the CP
      displacements. The postural behavior was assessed on the basis of basic CG(v) and
      CP - CG(v) movements estimated from the CP trajectories. The postural behavior
      observed during delayed CG(v) feedback was similar to the one observed with the
      similarly delayed CP movements feedback. On the other hand, the delayed CP -
      CG(v) feedback infers a decrease of the CP - CG(v) movements and concomitantly an
      increase of the CG(v) movements. This data highlight that there is enough
      information in the displayed CP trajectories to enable control of the CG and that
      providing CP - CG(v) information can lead the subjects to solely decrease these
      movements.

PMID- 17518278
TI  - Combining spatial filters for the classification of single-trial EEG in a finger
      movement task.
AB  - Brain-computer interface (BCI) is to provide a communication channel that
      translates human intention reflected by a brain signal such as
      electroencephalogram (EEG) into a control signal for an output device. In recent
      years, the event-related desynchronization (ERD) and movement-related potentials
      (MRPs) are utilized as important features in motor related BCI system, and the
      common spatial patterns (CSP) algorithm has shown to be very useful for ERD-based
      classification. However, as MRPs are slow nonoscillatory EEG potential shifts,
      CSP is not an appropriate approach for MRPs-based classification. Here, another
      spatial filtering algorithm, discriminative spatial patterns (DSP), is newly
      introduced for better extraction of the difference in the amplitudes of MRPs, and
      it is integrated with CSP to extract the features from the EEG signals recorded
      during voluntary left versus right finger movement tasks. A support vector
      machines (SVM) based framework is designed as the classifier for the features.
      The results show that, for MRPs and ERD features, the combined spatial filters
      can realize the single-trial EEG classification better than anyone of DSP and CSP
      alone does. Thus, we propose an EEG-based BCI system with the two feature sets,
      one based on CSP (ERD) and the other based on DSP (MRPs), classified by SVM.

PMID- 17518279
TI  - EEG-based lapse detection with high temporal resolution.
AB  - A warning system capable of reliably detecting lapses in responsiveness (lapses)
      has the potential to prevent many fatal accidents. We have developed a system
      capable of detecting lapses in real-time with second-scale temporal resolution.
      Data was from 15 subjects performing a visuomotor tracking task for two 1-hour
      sessions with concurrent electroencephalogram (EEG) and facial video recordings.
      The detector uses a neural network with normalized EEG log-power spectrum inputs
      from two bipolar EEG derivations, though we also considered a multichannel
      detector. Lapses, identified using a combination of video rating and tracking
      behavior, were used to train our detector. We compared detectors employing tapped
      delay-line linear perceptron, tapped delay-line multilayer perceptron (TDL-MLP),
      and long short-term memory (LSTM) recurrent neural networks operating
      continuously at 1 Hz. Using estimates of EEG log-power spectra from up to 4 s
      prior to a lapse improved detection compared with only using the most recent
      estimate. We report the first application of a LSTM to an EEG analysis problem.
      LSTM performance was equivalent to the best TDL-MLP network but did not require
      an input buffer. Overall performance was satisfactory with area under the curve
      from receiver operating characteristic analysis of 0.84 +/- 0.02 (mean +/- SE)
      and area under the precision-recall curve of 0.41 +/- 0.08.

PMID- 17518280
TI  - Detrended fluctuation analysis of EEG as a measure of depth of anesthesia.
AB  - For several decades, a number of methods have been developed for the noninvasive
      assessment of the level of consciousness during general anesthesia. In this
      paper, detrended fluctuation analysis is used to study the scaling behavior of
      the electroencephalogram as a measure of the level of consciousness. Three
      indexes are proposed in order to characterize the patient state. Statistical
      analysis demonstrates that they allow significant discrimination between the
      awake, sedated and anesthetized states. Two of them present a good correlation
      with established indexes of depth of anesthesia. The scaling behavior has been
      found related to the depth of anesthesia and the methodology allows real-time
      implementation, which enables its application in monitoring devices.

PMID- 17518281
TI  - A comparison of surface and intramuscular myoelectric signal classification.
AB  - The surface myoelectric signal (MES) has been used as an input to controllers for
      powered prostheses for many years. As a result of recent technological advances
      it is reasonable to assume that there will soon be implantable myoelectric
      sensors which will enable the internal MES to be used as input to these
      controllers. An internal MES measurement should have less muscular crosstalk
      allowing for more independent control sites. However, it remains unclear if this
      benefit outweighs the loss of the more global information contained in the
      surface MES. This paper compares the classification accuracy of six pattern
      recognition-based myoelectric controllers which use multi-channel surface MES as
      inputs to the same controllers which use multi-channel intramuscular MES as
      inputs. An experiment was designed during which surface and intramuscular MES
      were collected simultaneously for 10 different classes of isometric contraction.
      There was no significant difference in classification accuracy as a result of
      using the intramuscular MES measurement technique when compared to the surface
      MES measurement technique. Impressive classification accuracy (97%) could be
      achieved by optimally selecting only three channels of surface MES.

PMID- 17518282
TI  - Single-trial multiwavelet coherence in application to neurophysiological time
      series.
AB  - A method of single-trial coherence analysis is presented, through the application
      of continuous multiwavelets. Multiwavelets allow the construction of spectra and
      bivariate statistics such as coherence within single trials. Spectral estimates
      are made consistent through optimal time-frequency localization and smoothing.
      The use of multiwavelets is considered along with an alternative single-trial
      method prevalent in the literature, with the focus being on statistical,
      interpretive and computational aspects. The multiwavelet approach is shown to
      possess many desirable properties, including optimal conditioning, statistical
      descriptions and computational efficiency. The methods are then applied to
      bivariate surrogate and neurophysiological data for calibration and comparative
      study. Neurophysiological data were recorded intracellularly from two spinal
      motoneurones innervating the posterior biceps muscle during fictive locomotion in
      the decerebrated cat.

PMID- 17518283
TI  - Endothelial cell electrical impedance parameter artifacts produced by a gold
      electrode and phase sensitive detection.
AB  - Frequency dependent cellular micro-impedance estimates obtained from a gold two
      electrode configuration using phase sensitive detection have become increasingly
      used to evaluate cellular barrier model parameters. The results of this study
      show that cellular barrier function parameter estimates optimized using
      measurements obtained from this biosensor are highly susceptible to both time
      dependent and systematic instrumental artifacts. Based on a power spectral
      analysis of experimentally measured microelectrode voltages, synchronous, 60 Hz,
      and white Gaussian noise were identified as the most significant time dependent
      instrumental artifacts. The reduction of these artifacts using digital filtering
      produced a corresponding reduction in the optimized model parameter fluctuations.
      Using a series of instrumental circuit models, this study also shows that
      electrode impedance voltage divider effects and circuit capacitances can produce
      systematic deviations in cellular barrier function parameter estimates. Although
      the implementation of an active current source reduced the voltage divider
      effects, artifacts produced by coaxial cable and other circuit capacitive
      elements at frequencies exceeding 1 kHz still remained. Reducing time dependent
      instrumental fluctuations and systematic errors produced a significant reduction
      in cellular model barrier parameter errors and improved the model fit to
      experimental data.

PMID- 17518284
TI  - Body movement activity recognition for ambulatory cardiac monitoring.
AB  - Wearable electrocardiogram (W-ECG) recorders are increasingly in use by people
      suffering from cardiac abnormalities who also choose to lead an active lifestyle.
      The challenge presently is that the ECG signal is influenced by motion artifacts
      induced by body movement activity (BMA) of the wearer. The usual practice is to
      develop effective filtering algorithms which will eliminate artifacts. Instead,
      our goal is to detect the motion artifacts and classify the type of BMA from the
      ECG signal itself. We have recorded the ECG signals during specified BMAs, e.g.,
      sitting still, walking, movements of arms and climbing stairs, etc. with a single
      lead system. The collected ECG signal during BMA is presumed to be an additive
      mix of signals due to cardiac activities, motion artifacts and sensor noise. A
      particular class of BMA is characterized by applying eigen decomposition on the
      corresponding ECG data. The classification accuracies range from 70% to 98% for
      various class combinations of BMAs depending on their uniqueness based on this
      technique. The above classification is also useful for analysis of P and T waves
      in the presence of BMA.

PMID- 17518285
TI  - Ambulatory position and orientation tracking fusing magnetic and inertial
      sensing.
AB  - This paper presents the design and testing of a portable magnetic system combined
      with miniature inertial sensors for ambulatory 6 degrees of freedom (DOF) human
      motion tracking. The magnetic system consists of three orthogonal coils, the
      source, fixed to the body and 3-D magnetic sensors, fixed to remote body
      segments, which measure the fields generated by the source. Based on the measured
      signals, a processor calculates the relative positions and orientations between
      source and sensor. Magnetic actuation requires a substantial amount of energy
      which limits the update rate with a set of batteries. Moreover, the magnetic
      field can easily be disturbed by ferromagnetic materials or other sources.
      Inertial sensors can be sampled at high rates, require only little energy and do
      not suffer from magnetic interferences. However, accelerometers and gyroscopes
      can only measure changes in position and orientation and suffer from integration
      drift. By combing measurements from both systems in a complementary Kalman filter
      structure, an optimal solution for position and orientation estimates is
      obtained. The magnetic system provides 6 DOF measurements at a relatively low
      update rate while the inertial sensors track the changes position and orientation
      in between the magnetic updates. The implemented system is tested against a lab
      bound camera tracking system for several functional body movements. The accuracy
      was about 5 mm for position and 3 degrees for orientation measurements. Errors
      were higher during movements with high velocities due to relative movement
      between source and sensor within one cycle of magnetic actuation.

PMID- 17518286
TI  - Utilizing characteristic electrical properties of the epidermal skin layers to
      detect fake fingers in biometric fingerprint systems--a pilot study.
AB  - Electronic fingerprint systems are now gaining acceptance in mainstream consumer
      applications worldwide. It has been shown, however, that about 80% of these
      systems are easily fooled with different kinds of fake fingers with imprinted
      patterns. Hence, a live finger detection mechanism will be a crucial part of any
      fingerprint system used in security applications. We present such a system based
      on measurement of electrical characteristics of different layers of the skin.

PMID- 17518287
TI  - Ambulatory assessment of ankle and foot dynamics.
AB  - Ground reaction force (GRF) measurement is important in the analysis of human
      body movements. The main drawback of the existing measurement systems is the
      restriction to a laboratory environment. This paper proposes an ambulatory system
      for assessing the dynamics of ankle and foot, which integrates the measurement of
      the GRF with the measurement of human body movement. The GRF and the center of
      pressure (CoP) are measured using two six-degrees-of-freedom force sensors
      mounted beneath the shoe. The movement of foot and lower leg is measured using
      three miniature inertial sensors, two rigidly attached to the shoe and one on the
      lower leg. The proposed system is validated using a force plate and an optical
      position measurement system as a reference. The results show good correspondence
      between both measurement systems, except for the ankle power estimation. The root
      mean square (RMS) difference of the magnitude of the GRF over 10 evaluated trials
      was (0.012 +/- 0.001) N/N (mean +/- standard deviation), being (1.1 +/- 0.1)% of
      the maximal GRF magnitude. It should be noted that the forces, moments, and
      powers are normalized with respect to body weight. The CoP estimation using both
      methods shows good correspondence, as indicated by the RMS difference of (5.1 +/-
      0.7) mm, corresponding to (1.7 +/- 0.3)% of the length of the shoe. The RMS
      difference between the magnitudes of the heel position estimates was calculated
      as (18 +/- 6) mm, being (1.4 +/- 0.5)% of the maximal magnitude. The ankle moment
      RMS difference was (0.004 +/- 0.001) Nm/N, being (2.3 +/- 0.5)% of the maximal
      magnitude. Finally, the RMS difference of the estimated power at the ankle was
      (0.02 +/- 0.005) W/N, being (14 +/- 5)% of the maximal power. This power
      difference is caused by an inaccurate estimation of the angular velocities using
      the optical reference measurement system, which is due to considering the foot as
      a single segment. The ambulatory system considers separate heel and forefoot
      segments, thus allowing an additional foot moment and power to be estimated.
      Based on the results of this research, it is concluded that the combination of
      the instrumented shoe and inertial sensing is a promising tool for the assessment
      of the dynamics of foot and ankle in an ambulatory setting.

PMID- 17518288
TI  - Tapered conical polymer microneedles fabricated using an integrated lens
      technique for transdermal drug delivery.
AB  - Administration of protein and DNA biotherapeutics is limited by the need for
      hypodermic injection. Use of micron-scale needles to deliver drugs in a minimally
      invasive manner provides an attractive alternative, but application of this
      approach is limited by the need for suitable microneedle designs and fabrication
      methods. To address this need, this paper presents a conical polymer microneedle
      design that is fabricated using a novel integrated lens technique and analyzed
      for its ability to insert into the skin without mechanical failure. Microneedle
      master structures were fabricated using microlenses etched into a glass substrate
      that focused light through SU-8 negative epoxy resist to produce sharply tapered
      structures. Microneedle replicates were fabricated out of biodegradable polymers
      by micromolding. Because microneedle mechanical properties are critical to their
      insertion into the skin, we theoretically modeled two failure modes (axial mode
      and transverse mode), and analytical models were compared with measured data
      showing general agreement. Guided by this analysis, polymer microneedles were
      designed and demonstrated to insert to different depths into porcine skin in
      vitro. "Long" polymer microneedles were also demonstrated in human subjects to
      insert deeply without failure.

PMID- 17518289
TI  - EEG electrode caps can reduce SAR induced in the head by GSM900 mobile phones.
AB  - This paper investigates the influence of EEG electrode caps on specific
      absorption rate (SAR) in the head from a GSM900 mobile phone (217-Hz modulation,
      peak power output 2 W). SAR measurements were recorded in an anthropomorphic
      phantom using a precision robotic system. Peak 10 g average SAR in the whole head
      and in just the temporal region was compared for three phantom arrangements; no
      cap, 64-electrode "Electro-Cap," and 64-electrode "Quick-Cap". Relative to the
      "no cap" arrangement, the Electro-Cap and Quick-Cap caused a peak SAR (10 g)
      reduction of 14% and 18% respectively in both the whole head and in the temporal
      region. Additional computational modeling confirmed that SAR (10 g) is reduced by
      the presence of electrode leads and that the extent of the effect varies
      according to the orientation of the leads with respect to the radiofrequency (RF)
      source. The modeling also indicated that the nonconductive shell between the
      electrodes and simulated head material does not significantly alter the electrode
      lead shielding effect. The observed SAR reductions are not likely to be
      sufficiently large to have accounted for null EEG findings in the past but should
      nonetheless be noted in studies aiming to measure and report human brain activity
      under similar exposure conditions.

PMID- 17518290
TI  - Initial analysis of SAR from a cell phone inside a vehicle by numerical
      computation.
AB  - The purpose of this paper is to analyze the influence of the metallic structures
      of a realistic car body frame on the specific absorption rate (SAR) produced by a
      cell phone when a complete human body model is placed at different locations
      inside the vehicle, and to identify the relevant parameters responsible for these
      changes. The modeling and analysis of the whole system was conducted by means of
      computer simulations based on the full wave finite-difference time-domain (FDTD)
      numerical method. The excitation considered was an 835 MHz lambda/2 dipole
      located as a hands-free communication device or as a hand-held portable system.
      We compared the SAR at different planes on the human model, placed inside the
      vehicle with respect to the free space situation. The presence of the car body
      frame significantly changes the SAR distributions, especially when the dipole is
      far from the body. Although the results are not conclusive on this point, this
      change in SAR distribution is not likely to produce an increase above the limits
      in current guidelines for partial body exposure, but may be significant for whole
      body exposure. The most relevant change found was the change in the impedance of
      the dipole, affecting the radiated power. A complementary result from the
      electromagnetic computations performed is the change in the electromagnetic field
      distribution inside a vehicle when human bodies are present. The whole vehicle
      model has been optimized to provide accurate results for sources placed inside
      the vehicle, while keeping low requirements for computer storage and simulation
      time.

PMID- 17518291
TI  - Glucose concentration can be predicted ahead in time from continuous glucose
      monitoring sensor time-series.
AB  - A clinically important task in diabetes management is the prevention of
      hypo/hyperglycemic events. In this proof-of-concept paper, we assess the
      feasibility of approaching the problem with continuous glucose monitoring (CGM)
      devices. In particular, we study the possibility to predict ahead in time glucose
      levels by exploiting their recent history monitored every 3 min by a minimally
      invasive CGM system, the Glucoday, in 28 type 1 diabetic volunteers for 48 h.
      Simple prediction strategies, based on the description of past glucose data by
      either a first-order polynomial or a first-order autoregressive (AR) model, both
      with time-varying parameters determined by weighted least squares, are
      considered. Results demonstrate that, even by using these simple methods, glucose
      can be predicted ahead in time, e.g., with a prediction horizon of 30 min
      crossing of the hypoglycemic threshold can be predicted 20-25 min ahead in time,
      a sufficient margin to mitigate the event by sugar ingestion.

PMID- 17518292
TI  - Reduced-order preconditioning for bidomain simulations.
AB  - Simulations of the bidomain equations involve solving large, sparse, linear
      systems of the form Ax = b. Being an initial value problems, it is solved at
      every time step. Therefore, efficient solvers are essential to keep simulations
      tractable. Iterative solvers, especially the preconditioned conjugate gradient
      (PCG) method, are attractive since memory demands are minimized compared to
      direct methods, albeit at the cost of solution speed. However, a proper
      preconditioner can drastically speed up the solution process by reducing the
      number of iterations. In this paper, a novel preconditioner for the PCG method
      based on system order reduction using the Arnoldi method (A-PCG) is proposed.
      Large order systems, generated during cardiac bidomain simulations employing a
      finite element method formulation, are solved with the A-PCG method. Its
      performance is compared with incomplete LU (ILU) preconditioning. Results
      indicate that the A-PCG estimates an approximate solution considerably faster
      than the ILU, often within a single iteration. To reduce the computational
      demands in terms of memory and run time, the use of a cascaded preconditioner was
      suggested. The A-PCG was applied to quickly obtain an approximate solution, and
      subsequently a cheap iterative method such as successive overrelaxation (SOR) is
      applied to further refine the solution to arrive at a desired accuracy. The
      memory requirements are less than those of direct LU but more than ILU method.
      The proposed scheme is shown to yield significant speedups when solving time
      evolving systems.

PMID- 17518293
TI  - A rod matrix compensator for small-field intensity modulated radiation therapy: a
      preliminary phantom study.
AB  - A compensator made of a tungsten-based rod matrix has been proposed for small
      field intensity modulated radiation therapy. The compensator was attached to a 6
      MV linac gantry head. The proposed compensator could modulate the X-ray intensity
      with a step of 10% and a minimum transmission of 2.5%.

PMID- 17518294
TI  - Real-time correction of heart interbeat intervals.
AB  - Heart rate variability (HRV) is traditionally analyzed while a subject is in a
      controlled environment, such as at rest in a clinic, where it can be used as a
      medical indicator. This paper concerns analyzing HRV outside of controlled
      environments, such as on an actively moving person. We describe automated methods
      for inter-heartbeat interval (IBI) error detection and correction. We collected
      124,998 IBIs from 18 subjects, undergoing a variety of active motions, for use in
      evaluating our methods. Two human graders manually labeled each IBI, evaluating
      10% of the IBIs as having an error, which is a far greater error percentage than
      has been examined in any previous study. Our automated method had a 96% agreement
      rate with the two human graders when they themselves agreed, with a 49% rate of
      matching specific error corrections and a 0.01% false alarm rate.

PMID- 17518295
TI  - Forward Euler stability of the bidomain model of cardiac tissue.
AB  - The bidomain model describes the anisotropic electrical properties of cardiac
      tissue. One common numerical technique for solving the bidomain equations is the
      explicit forward Euler method. In this communication we derive a relationship
      between the time and space steps that ensures the stability of this numerical
      method.

PMID- 17518296
TI  - In vivo inductive phase shift measurements to detect intraperitoneal fluid.
AB  - Four different volumes of physiological saline were infused into the abdominal
      cavity of rats and the resulting inductive phase shift in the bulk of the abdomen
      was measured with a noncontact electrical induction system, built to measure
      phase shift in the bulk of the body in the frequency range from 1 MHz to 8.5 MHz.
      This experimental study shows that inductive bulk measurements of phase shift
      have the potential to detect changes in intraperitoneal fluid in vivo with
      measurements made at frequencies higher than approximately 1 MHz. The experiments
      also show that the bulk phase shift increases as a function of frequency and
      fluid volume in a way that is qualitatively consistent with earlier theoretical
      predictions.

PMID- 17518297
TI  - An approach for the estimation of contact force on a human head induced by a
      foreign-object impact.
AB  - This paper presents a novel approach to estimate the contact force on a human
      head induced by a foreign-object impact. A simple head-striker model is proposed
      to describe the contact between the human head and the foreign-object striker.
      Based on the head-striker model, a contact force function is formulated, which is
      expressed by the head and striker material properties and the impact velocity.
      The contact force predicted by present method is compared with the previous
      published experimental data. A good agreement of the simulation results with the
      experimental data shows the feasibility of the present approach.

PMID- 17518298
TI  - Improved heat transfer modeling of the eye for electromagnetic wave exposures.
AB  - This study proposed an improved heat transfer model of the eye for exposure to
      electromagnetic (EM) waves. Particular attention was paid to the difference from
      the simplified heat transfer model commonly used in this field. From our
      computational results, the temperature elevation in the eye calculated with the
      simplified heat transfer model was largely influenced by the EM absorption
      outside the eyeball, but not when we used our improved model.

PMID- 17518299
TI  - Epidemiology and education: using public health for teaching mathematics and
      science.

PMID- 17518300
TI  - The New Mexico Clinical Prevention Initiative: a statewide prevention
      partnership.
AB  - The New Mexico Department of Health and the New Mexico Medical Society invited
      organizations to participate in an initiative to promote clinical preventive
      services. The Clinical Preventive Initiative (CPI) focuses on the following
      interventions based on burden of illness, preventability of the condition, cost,
      current level of services, availability of leadership, and programmatic support:
      adult pneumococcal vaccination, tobacco use prevention and cessation, mammography
      screening, colorectal cancer screening, healthier weight, screening and treatment
      for chlamydia and gonorrhea, screening and intervention for problem drinking,
      childhood immunization, and prevention of unintended pregnancy. Specific
      workgroups plan and implement interventions directed at New Mexico medical
      practices, practitioners, and health-care systems. Several state measures suggest
      effectiveness of CPI efforts. CPI is a successful public-private collaboration
      providing an active forum for statewide clinical prevention policy development,
      an effective mechanism to achieve greater awareness of prevention and improved
      delivery of preventive services.

PMID- 17518301
TI  - Baseline assessment of public health informatics competencies in two Hudson
      Valley health departments.
AB  - Information technology has the capability to improve the way public health is
      practiced. Realization of this potential is possible only with a workforce ready
      to utilize these technologies. This project team assessed informatics
      competencies of employees in two county departments of health. The goal was to
      determine the status quo in terms of informatics competencies by surveying
      current levels of proficiency and relevance, and identify areas of needed
      training. A survey was adapted from the recommendations of a Working Group
      document by the Centers for Disease Control and Prevention and administered to
      all employees in the two health departments. Respondents evaluated proficiency
      and relevance for each of 26 recommended competencies. A gap score was generated
      between these two measures; results were compared to the recommendations of the
      Working Group. The following data for each job level are presented: mean gap
      scores by competency class; the percentage of respondents demonstrating a gap in
      the competencies reported to be most relevant; and the percentage of respondents
      meeting the target recommendations of the Working Group. The percentage of
      respondents who reached the targets was low in higher-level staff. And overall,
      employees reported low levels of relevance for most of the competencies. The
      average public health employee does not feel that prescribed informatics
      competencies are relevant to their work. Before the public health system can take
      advantage of information technology, relevant employee skills should be
      identified or developed. There needs to be a shift in thinking that will
      recognize the promise of information technology in everyday work.

PMID- 17518302
TI  - Survey of state practices during the 2004-2005 influenza vaccine shortage.
AB  - To describe state-level actions and policies during the 2004-2005 influenza
      vaccine shortage and determine whether these or other factors were related to
      vaccination coverage, we surveyed all state health departments (including the
      District of Columbia). We included 2004-2005 Behavioral Risk Factor Surveillance
      System data to examine whether state-level actions, policies, or other factors
      like vaccine supply were related to changes in vaccination coverage in adults
      aged > or = 65 years from the previous non-shortage year. We found that 96% (n =
      49) of states reported adopting or recommending adherence to the initial national
      interim influenza vaccination recommendations. Of these, at some point during the
      season, 22% (n = 11) reported local public health agencies issued prioritization
      recommendations that differed from the state health department's guidance. Eighty
      percent (n = 41) initiated at least one emergency response activity and 43% (n =
      22) referred to or implemented components of their pandemic influenza plans. In
      35% (n = 18), emergency or executive orders were issued or legislative action
      occurred. In a multivariable linear regression model, the availability and use of
      practitioner contact lists and having a relatively high vaccine supply in early
      October 2004 were associated with smaller decreases in coverage for adults aged >
      or = 65 years from the previous non-shortage season (p = 0.003, r2 = 0.26).
      States over-whelmingly followed national vaccination prioritization guidelines
      and used a range of activities to manage the 2004-2005 vaccine shortage. The
      availability and use of practitioner contact lists and having a relatively high
      vaccine supply early in the season were associated with smaller decreases in
      coverage from the previous non-shortage season.

PMID- 17518303
TI  - Changes in driver fatality rates and vehicle incompatibility concurrent with
      changes in the passenger vehicle fleet.
AB  - OBJECTIVE: With more sport utility vehicles (SUVs) on the road, public concern
      has been expressed about their influence on traffic safety. The present study
      examined changes in the mix of passenger vehicles between 1988 and 2004 and
      concurrent changes in driver fatality rates and vehicle incompatibility. METHOD:
      Vehicle registrations and driver deaths per registered vehicle were examined
      using data from R.L. Polk and Company and the Fatality Analysis Reporting System.
      RESULTS: Between 1988 and 2004, SUVs comprised an increasingly larger proportion
      of registered passenger vehicles (5% of one- to three-year-old vehicles in 1988
      vs. 22% in 2004), yet driver deaths per registered vehicle decreased 43% to 47%
      for all passenger vehicle types. Reductions in driver fatality rates were greater
      for two-vehicle crashes than for single-vehicle crashes and greater for two
      vehicle frontal crashes than for two-vehicle side-impact crashes. Driver death
      rates declined more on rural roads than on urban roads, and this difference was
      most pronounced for SUVs. Among cars struck by other vehicles, driver death rates
      in front-to-front and front-to-side impacts decreased more when the striking
      vehicle was an SUV than a pickup or car. CONCLUSIONS: Factors likely contributing
      to the overall reductions in fatality rates include advances in occupant
      protection, increases in average vehicle weight, increased availability of SUVs
      with car-based designs, and reductions in alcohol-impaired driving. Reductions of
      driver death rates in two-vehicle collisions between 1988 and 2004 are
      encouraging, but SUVs and pickups continue to pose a substantially higher risk to
      drivers of cars than when the striking vehicle is another car.

PMID- 17518304
TI  - Development of a survey instrument to measure connectivity to evaluate national
      public health preparedness and response performance.
AB  - OBJECTIVE: Survey instruments for evaluating public health preparedness have
      focused on measuring the structure and capacity of local, state, and federal
      agencies, rather than linkages among structure, process, and outcomes. To focus
      evaluation on the latter, we evaluated the linkages among individuals,
      organizations, and systems using the construct of "connectivity" and developed a
      measurement instrument. METHODS: Results from focus groups of emergency
      preparedness first responders generated 62 items used in the development sample
      of 187 respondents. Item reduction and factors analyses were conducted to confirm
      the scale's components. RESULTS: The 62 items were reduced to 28. Five scales
      explained 70% of the total variance (number of items, percent variance explained,
      Cronbach's alpha) including connectivity with the system (8, 45%, 0.94),
      coworkers (7, 7%, 0.91), organization (7, 12%, 0.93), and perceptions (6, 6%,
      0.90). Discriminant validity was found to be consistent with the factor
      structure. CONCLUSION: We developed a Connectivity Measurement Tool for the
      public health workforce consisting of a 34-item questionnaire found to be a
      reliable measure of connectivity with preliminary evidence of construct validity.

PMID- 17518305
TI  - Injury mortality rates in Native and non-Native children: a population-based
      study.
AB  - OBJECTIVES: To examine injury mortality rates in Native and non-Native children
      in the province of Alberta, Canada, over a 10-year period, temporal trends in
      injury mortality rates (Native vs. non-Native), as well as relative risks of
      injury mortality (Native vs. non-Native) by injury mechanism and intent, were
      calculated. METHODS: An observational, population-based study design was used.
      Mortality data were obtained from provincial vital statistics, with injury deaths
      identified using external injury codes (E-codes). The relative risk (RR) of
      injury mortality (Native vs. non-Native) along with 95% confidence intervals
      (CIs) were calculated. Stratified analyses and Poisson regression modeling were
      used to calculate adjusted relative risk. RESULTS: Injury mortality rates
      declined over the study period, with no difference in the rate of decline between
      Native and non-Native children. The adjusted relative risk for all-cause injury
      death (Native vs. non-Native) was 4.6 (95% CI 4.1 to 5.2). The adjusted relative
      risks (Native vs. non-Native) by injury intent categories were: unintentional
      injuries, 4.0 (95% CI 3.5 to 4.6); suicide, 6.6 (95% CI 5.2 to 8.5); and
      homicide, 5.1 (95% CI 3.0 to 8.5). Injury mortality rates were consistently
      higher for Native children across all injury mechanism categories. The largest
      relative risks (Native vs. non-Native) were pedestrian injury (RR = 17.0),
      accidental poisoning (RR = 15.4), homicide by piercing objects (RR = 15.4), and
      suicide by hanging (RR = 13.5). CONCLUSION: The burden of injury mortality is
      significantly greater in Native children compared with non-Native children.
      Therefore, injury prevention strategies that target both intentional and
      unintentional injuries are needed.

PMID- 17518306
TI  - Perceived discrimination among severely disadvantaged people with HIV infection.
AB  - OBJECTIVES: Studies continue to document that people with human immunodeficiency
      virus (HIV) experience discrimination in their interactions with the health-care
      system, which can have negative implications for maintaining continuity in care
      and outcomes. We explored the patient characteristics associated with perceived
      discrimination and whether these experiences are associated with health-care
      system quality ratings in a survey of severely disadvantaged people with HIV who
      are at great risk of inconsistent access to appropriate health care. METHODS:
      Five hundred and twenty-three participants were recruited from temporary housing
      facilities for people with HIV in the New York City area and administered a
      survey using audio computer-assisted self-interviewing technology. RESULTS: Of
      the 207 participants (39.6%) who reported experiencing discrimination in the
      health-care system, the most common attributions were HIV infection (n = 122,
      59.8%), drug use (n = 100, 49.8%), homelessness (n = 71, 34.6%), and
      race/ethnicity (n = 69, 35.2%). Length of time HIV infected, use of non
      prescription opioids, white race, higher education, female gender, younger age,
      and poorer self-reported health status were all significantly associated with
      greater odds of perceived discrimination. After adjusting for participant
      characteristics, perceived discrimination was significantly associated with
      poorer participant ratings of quality of health care. CONCLUSIONS: Members of
      this vulnerable population commonly report experiences of discrimination from
      within the health-care system and these experiences are associated with poor
      health-care ratings. These findings support the need for closer examination of
      the adequacy of cultural competency training within the HIV health-care delivery
      system to improve access to appropriate care for disadvantaged people.

PMID- 17518307
TI  - Exposure to West Nile virus during the 2002 epidemic in Cuyahoga County, Ohio: a
      comparison of pediatric and adult behaviors.
AB  - OBJECTIVES: Emerging evidence suggests that children are at higher risk for West
      Nile virus (WNV) exposure, but may have a lower risk for infection-related
      morbidity and mortality. Limited data exist regarding risk determinants of
      childhood WNV infection. We conducted a survey to analyze the differences between
      pediatric and adult behavior relevant to WNV exposure. METHODS: Residents of
      participating sampled households responded to a questionnaire that measured
      knowledge, attitudes, personal protective behaviors, and clinical history to
      evaluate the association between personal behavior and exposure to WNV. RESULTS:
      Children were more likely to have high levels of outdoor exposure compared to
      adults (83% vs. 70%). Children were less likely to avoid going outdoors (4% vs.
      13%) and to wear long sleeves or pants compared to adults (8% vs. 19%). Both
      groups were highly educated about WNV. Television, not health-care provider
      education, was the most common source of WNV information. Participants were more
      concerned about WNV infection than pesticide usage. CONCLUSIONS: Our study
      demonstrates that children exhibit behaviors that could put them at greater risk
      for WNV infection and suggests that children could benefit from greater education
      about practices that can decrease WNV exposure to limit their risk for infection.

PMID- 17518308
TI  - Racially disproportionate admission rates for ambulatory care sensitive
      conditions in North Carolina.
AB  - OBJECTIVE: This study examines race variations in quality of care through the
      proxy of ambulatory care sensitive (ACS) conditions. Hospital admission rates for
      eight ACS conditions were examined for African American and white Medicare
      beneficiaries in North Carolina. Temporal variations for ACS were also examined.
      METHOD: Enrollment and inpatient claims files from the Centers for Medicare and
      Medicaid Services (CMS) for a 1999-2002 cohort who were aged 65 years or older in
      1999 were examined. Descriptive statistics were computed for each year. Cochran
      Mantel Haenszel tests were performed to assess differences in the admission rates
      for both individual and aggregate ACS conditions controlling for time. The
      Cochran-Armitage test for trend was used to evaluate changes in admission rates
      over time. RESULTS: African Americans had higher admission rates for five of the
      eight ACS conditions. The highest rates were for diabetes among African Americans
      (odds ratio [OR] = 2.86; 95% confidence interval [CI] [2.73, 2.99]) and adult
      asthma (OR = 1.51; 95% CI [1.43, 1.61]). African Americans tended to have lower
      ACS admission rates than white patients for chronic obstructive pulmonary disease
      (OR = 0.67; 95% CI [0.65, 0.69]); bacterial pneumonia (OR = 0.86; 95% CI [0.84,
      0.89]), and angina (OR = 0.90; 95% CI [0.84, 0.97]). CONCLUSIONS: Using the ACS
      proxy for quality of health care as applied to examining race and ethnicity is a
      promising approach, though challenges remain. Admissions for ACS conditions
      between African American and white patients differ, but it is unclear why. This
      exploratory study must lead to an examination of social, economic, historical,
      and cultural factors for preventive, remedial, and beneficial policy initiatives.

PMID- 17518309
TI  - Investigating asthma deaths among children and young adults: Michigan Asthma
      Mortality Review.
AB  - OBJECTIVE: We developed a surveillance system to investigate asthma deaths in
      children and young adults. METHODS: A rapid asthma death notification and
      investigation system for Michigan was developed to identify interventions to
      prevent future deaths among people aged 2-34 years. Multidisciplinary panels to
      determine causal factors and recommend preventative actions reviewed information
      from death certificates, autopsies, next-of-kin interviews, and medical records.
      An annual report was disseminated to public health workers, health-care
      providers, insurers, and others. RESULTS: Eighty-six asthma deaths in Michigan
      residents, aged 2-34, occurred from 2002-2004. Sixty-one next of kin were
      interviewed and medical records were obtained for 84 of the deceased. Summaries
      were prepared on each of the deceased and were reviewed by expert panels, which
      reached consensus on causal factors and potential preventive action for each
      death. Each year an annual report, which summarized the causal factors and
      potential preventive activity, was prepared. CONCLUSION: This review has informed
      and catalyzed interventions to improve asthma care and management in Michigan.
      Factors leading to the review's success and future activities are discussed.

PMID- 17518310
TI  - Racial misidentification of American Indians/Alaska Natives in the HIV/AIDS
      Reporting Systems of five states and one urban health jurisdiction, U.S., 1984
      2002.
AB  - OBJECTIVES: We examined racial misidentification of American Indians/Alaska
      Natives (AI/AN) reported to the human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS) Reporting Systems (HARS) of five U.S. states and
      one county. METHODS: To identify AI/AN records with misidentified race, we linked
      HARS data from 1984 through 2002 to the Indian Health Service National Patient
      Information and Reporting System (NPIRS), excluding non-AI/AN dependents, using
      probabilistic matching with clerical review. We used chi-square tests to examine
      differences in proportions and logistic regression to examine the associations of
      racial misidentification with HARS site, degree of AI/AN ancestry, mode of
      exposure to HIV, and urban or rural location of residence at time of diagnosis.
      RESULTS: A total of 1,523 AI/AN individuals was found in both NPIRS and HARS;
      race was misidentified in HARS for 459 (30%). The percentages of racially
      misidentified ranged from 3.7% (in Alaska) to 55% (in California). AI/AN people
      were misidentified as white (70%), Hispanic (16%), black (11%), and Asian/Pacific
      Islander (2%); for 0.9%, race was unspecified. Logistic regression results (data
      from all areas, all variables) indicated that urban residence at time of
      diagnosis, degree of AI/AN ancestry, and mode of exposure to HIV were
      significantly associated with racial misidentification of AI/AN people reported
      to HARS. CONCLUSIONS: Our findings add to the evidence that racial
      misidentification of AI/AN in surveillance data can result in underestimation of
      AI/AN HIV/AIDS case counts. Racial misidentification must be addressed to ensure
      that HIV/ AIDS surveillance data can be used as the basis for equitable resource
      allocation decisions, and to inform and mobilize public health action.

PMID- 17518311
TI  - Providing naloxone to substance users for secondary administration to reduce
      overdose mortality in New York City.

PMID- 17518312
TI  - Public health, culture, and colonial medicine: smallpox and variolation in
      Palestine during the British Mandate.

PMID- 17518313
TI  - Health-care utilization among empty-nesters in the rural area of a mountainous
      county in China.

PMID- 17518314
TI  - Public health "malpractice" and the obesity epidemic.

PMID- 17518315
TI  - Identifying and protecting vulnerable populations in public health emergencies:
      addressing gaps in education and training.

PMID- 17518316
TI  - Let's explore a truly free market, consumer driven health care system.

PMID- 17518317
TI  - Charging interest on patient accounts--caution!

PMID- 17518318
TI  - Democratic priorities take center stage.

PMID- 17518319
TI  - The future: medicare reimbursement and quality measures.

PMID- 17518320
TI  - Free clinics and Iowa's uninsured: the last safety net.

PMID- 17518321
TI  - Emergency preparedness for office-based surgery.

PMID- 17518322
TI  - Can money really buy happiness?

PMID- 17518323
TI  - [Surgical approach of the functional post-partial gastrectomy syndromes].
AB  - AIM OF THE STUDY: Post-gastrectomy syndromes (PGS) are iatrogenic conditions
      which may arise from partial gastrectomies, independently from their indications
      (cancer or ulcer) and the reconstruction technique (Billroth I, Billroth II or
      Roux-en-Y). They are usually less frequent in patients with a Roux-en-Y
      reconstruction, but also this technique does not surely prevent SPG. Recently,
      some new technique have been proposed in order to prevent the PGS. Most of them
      are based upon a less extensive resection of the viscus, replaced by application
      of simple stapler mediated interruptions (the so called "uncut" technique). We
      aimed to verify whether such less invasive technique were also able to exert a
      therapeutic role for various type of PGS with the same efficiency of the
      traditional ri-resection techniques, which are known to generally have a major
      morbidity impact. MATERIAL AND METHODS: Nineteen patients, 12 male and 7 female,
      aged between 44 and 67 years, have been operated since 1985 up to 2004. All of
      them had an overt SPG (2 with efferent loop syndrome, 10 with gastro-esophageal
      biliary reflux, 3 with an afferent loop disease and, finally, 4 with a late
      dumping disease. The series has been divided into two groups depending on the
      type of surgical technique we chose for the correction of their SPG: "high
      surgery" patients (HS), operated with Roux re-resection and TADE, "low surgery"
      (LS) patients treated with "uncut" techniques and or Braun/GEA anastomosis. Both
      group were comparatively analyzed for the surgical outcome using an Eckhauser and
      a Visick scale. RESULTS: Out of the 11 patients of the first group 8 had a Roux
      ri-resection and 3 a TADE, whereas subjects from the second group underwent in
      four cases to a Braun/uncut afferent loop closer, which was associated to a GEA
      in the remnant ones. In both group there was no mortality rate, whereas only one
      subjects from the HS group had a post-operative complication. Either the Visick
      and the Eckauser score was better in the LS group. DISCUSSION: Data collected
      show that SPG, even if represented an heterogeneous group of clinical conditions,
      can be generally treated following a surgical procedure as conservative as
      possible. Such conclusion may open further views in the laparoscopic management
      of SPG.

PMID- 17518324
TI  - [Some ecomorphologic aspects of nodular goiter].
AB  - AIM OF THE STUDY: Determine microcalcifications' rule in nodular goiter, to
      classify those calcifications and identify US features suspect for tumoral
      pathology. MATERIAL AND METHODS: In Endocrine Surgery Unit we
      ultrasonographically detected 655 patients in a period of twelve months (Jan to
      Dec 2005). Patients aged from 22 to 75 years. Multinodular goiter were 42% and
      solitary nodular 33.8%, higher than other studies, as we checked selected
      patients. We determined microcalcification' incidence in nodular goiter and
      thyroiditis and studied their correlations with tumours. We also studied other US
      features suspect for malignant lesions. We divided microcalcifications in four
      groups. Thyroiditis prevalence was 55.8%. Microcalcifications' prevalence was
      32.3%, divided as follow: Type I 18.1%, type II 4%, type III 81.8%, type IV 9%.
      In 9% of patients was present more than one kind of calcifications.
      Microcalcification rate was 28.9% in inflammatory disease, 55.17% in multinodular
      goiter and 18, 18% in single thyroid nodules. "Suspect" microcalcifications were
      present in 9% of whole thyroid pathology and in 12% of MNG. The majority of
      microcalcifications belonged to type III and their nature is questionable.
      Several Authors mentioned microcalcifications as a sensitive and highly specific
      feature for tumour diagnosis. Microcalcifications have a 59.2% sensitivity rate
      and a specificity rate of 85.8-95%. Their diagnostic accuracy is 77.4%. Other us
      suspect features are hypoecogenicity and irregular nodule outline. CONCLUSIONS:
      Ultrasonography remains an operator-dependent exam and it's necessary a correct
      interpretation of morphological data. Meticulous characterization of all
      ultrasonographic criteria enounced above is useful to reach satisfactory results
      and identify suspect lesions.

PMID- 17518325
TI  - Spontaneous pneumothorax. When and how to treat.
AB  - INTRODUCTION: Spontaneous pneumothorax, whether primary or secondary, may occur
      in patients with or without a history of pneumonic disease. AIM OF THE STUDY:
      From 1992 to 2002, we treated 275 patients, 230 male and 45 female, in the
      department of Thoracic Surgery of the General Hospital of Nikaia-Piraeus. In this
      study the Authors report the data concerning the frequency correlated with age,
      sex, causes, symptoms, as well as the ways of treatment, in order to compare them
      and their results with those recorded in Greek and international literature.
      CONCLUSIONS: It is made obvious by our material that only approximately 10% of
      patients suffering from spontaneous pneumothorax need surgery (thoracotomy),
      while the remaining patients can be managed with closed thoracic drainage or
      conservative treatment and monitoring.

PMID- 17518326
TI  - [Extra-ampullary duodenal neoplasms].
AB  - The authors report on twelve cases of non-ampullary duodenal neoplasm and remark
      the rarity of this pathology. According to the literature, the traditional
      endoscopy is the mainstay diagnostic test, because of aspecific digestive
      symptoms, but the authors stress the importance of the "longue" endoscopy or
      endoscopy integrated with duodenography in non-responders patients who had non
      diagnostic traditional endoscopy for neoplasm. Duodeno-cephalo-pancreatectomy and
      segmentary duodenal resection are proposed by tumor site. Better results for
      prognosis can be obtained only with an early diagnosis and radical surgical
      therapy, because of chemotherapy and radiotherapy don't improve survival.

PMID- 17518327
TI  - The bilio-intestinal bypass.
AB  - BACKGROUND: Since 1990 we adopted the bilio-intestinal bypass (BIBP) for all
      morbid obese patients eligible to a malabsorption procedure. Since 2001 we used
      laparoscopic technique. MATERIALS AND METHODS: 102 patients; mean age 35.4 (18
      54) years; preoperative mean weight Kg 148.3 (105-225); mean preoperative BMI
      54.1 kg/m2 (40-66.2); mean follow-up 10 years (1-22). 83 patients underwent open
      and 19 laparoscopic BIBP. The operation was performed with five lap ports.
      Section of the jejunum 30 cm from the Treitz and of mesentery was made by linear
      stapler. The cholecysto-jejunal anastomosis was completed with 45 mm linear
      stapler. A side-to-side anastomosis between the proximal jejunum and the last 12
      18 cm of the ileum was created by firing a 60 mm linear stapler. On the excluded
      ileum an anti-reflux valve system was hand-sutured. RESULTS: Five years post
      operatively mean weight was 89 (62-130) kg, mean BMI was 31 (24-41) kg/m2. Two
      patients of the 19 laparoscopic patients were converted in open surgery for
      adhesions post-appendectomy. The main late complications were incisional hernia
      (19.3%) and abdominal bloating (2.9%). The reversal and conversion rate was 65%.
      There was no death. CONCLUSION: Our experience showed that five years post-BIBP
      the weight loss was satisfactory in 90.7% of patients. Using laparoscopic
      technique it is possible to reduce pain, in-hospital time, respiratory and
      thromboembolic complications, convalescence and incisional hernia.

PMID- 17518328
TI  - [Extraordinary role of self-expanding metal stent (SEMS) in the malignant
      colorectal obstruction: different care in two cases].
AB  - The colorectal cancer presents with bowel obstruction in 10%-30% of patients.
      Established treatment of this evolutive condition, until 15 years ago, was
      emergency surgery. Primary resection with or without ileostomy, staged resection,
      Hartmann's procedure, or definitive colostomy are the therapeutical options.
      There is ongoing controversy on the best procedure to apply, because the choice
      depends on the patient's condition, age, electrolyte imbalances, nutritional
      status, obstructional grade, comorbidity and surgeon's attitude. However, the
      obstruction and the emergency operation add risk of complications and mortality
      instead of elective surgery. The efficacy of self-expanding metal stent to solve
      the obstruction had recently changed the management of malignant luminal
      obstruction: it is safe, effective, with very low mortality, low morbidity and
      also cheap. In the inoperable cases it represents the first line therapy avoiding
      the colostomy. In the operable patients, instead of two-step surgery, the SEMS
      had to be preferred because is a one-time and election surgery and avoid
      colostomy too, even if temporary. SEMS versus emergency primary surgery, without
      randomized and controlled study, allows a safer single-staged surgery. Finally it
      improves the quality of life avoiding colostomy, and reducing operative risk. We
      present two different use of SEMS: the palliation in inoperable patient and the
      "bridge to surgery" in critical obstructed patient.

PMID- 17518329
TI  - [The education of the trauma surgeon: the "trauma surgery course" as advanced
      didactic tool].
AB  - BACKGROUND: The consequences of low incidence of penetrating injuries in Europe
      and of the increasing in nonoperative management of blunt trauma are a decrease
      in surgeons' confidence for managing traumatic injuries. The Corso Teorico
      Pratico di Chirurgia del Politrauma was developed as model for teaching operative
      trauma techniques. The aim of this retrospective study is to evaluate the
      effectiveness of the course and compare it with other similar courses. METHOD:
      The Corso Teorico Pratico di Chirurgia del Politrauma is a two day course and
      consists of lecture on trauma topics and porcine operative experience. Data on
      the first 124 participants were collected and analyzed. RESULTS: One hundred
      twenty general surgeons and 2 pediatric surgeons had participated at the course.
      All the participants judged the course an efficient model to improve knowledge on
      surgical treatment of trauma. CONCLUSION: A two days course, focused on trauma,
      with didactic lectures and operative life-like situations, can be a model for
      simulated education and useful to improve surgeons' confidence in trauma
      patients.

PMID- 17518330
TI  - Agenesis of the gallbladder.
AB  - Agenesis of the gallbladder is a rare anomaly that is usually asymptomatic, but
      sometimes the patients may have symptoms compatible with a biliary disorder like
      cholelithiasis. Its preoperative diagnosis is often difficult, especially if
      dysplastic cyst is associated and simulates the gallbladder. When the diagnosis
      is doubtful its confirmation and treatment of dysplastic cyst require open
      surgery, careful dissection of the common bile duct to avoid biliary lesions and
      intraoperative ultrasonography or cholangiography to be performed to exclude
      other associated anomalies. The Authors describe the case of agenesis of
      gallbladder and dysplastic cyst associated and comment on its clinical,
      diagnostic, and therapeutic aspects.

PMID- 17518331
TI  - [Gallbladder injury].
AB  - The Authors report on a rare case of blunt traumatic injury of the gallbladder. A
      careful clinical examination, an abdominal ultrasonography and a contrast
      material-enhanced computed tomography have a primary importance for a correct
      diagnosis. Laparoscopic surgery has an important diagnostic and, in selected
      cases, therapeutic role. In all traumatic gallbladder ruptures, after an accurate
      search of eventual associated injuries of other abdominal organs, cholecystectomy
      is considered the treatment of choice.

PMID- 17518332
TI  - [Surgical therapy of hepatic fibrolamellar carcinoma].
AB  - Hepatic fibrolamellar carcinoma (FLC) is an uncommon tumour that differs from
      hepatocellular carcinoma (HCC) in demographics, condition of the affected liver,
      tumour markers, and prognosis. FLC characteristically manifests as a large
      hepatic mass in adolescents or young adults with female predominance (mean age 23
      years). Cirrhosis, elevated alpha-fetoprotein levels, and risk factors for HCC
      such as viral hepatitis are typically absent. FLC is usually associated with
      serum tumour markers such as vitamin B12 binding protein, and neurotensin. FLC is
      characterized pathologically by cords of tumour cells surrounded by abundant
      collagenous fibrous tissue arranged in a parallel or lamellar distribution. FLC
      usually appears on radiologic images as a lobulated heterogeneous mass with a
      central scar in an otherwise normal liver. The clinical presentation of patients
      with FLC is variable. These patients commonly have pain, and palpable right upper
      quadrant abdominal mass. An uncommon presenting sign is gynaecomastia in men. Use
      of percutaneous biopsy (FNAB) is beneficial if there is diagnostic uncertainty
      about the radiologic diagnosis (US, CT MRI). Although FLC is frequently
      recurrent, patients have a better prognosis than those with HCC, and aggressive
      surgical liver resection with extended lymphadenectomy or liver transplantation
      may be indicated. The presence of advanced-stage disease, direct invasion of
      adjacent organs, lymphadenopathy, or limited metastasis does not preclude
      attempts at curative resection. In inoperable cases, the patient may benefit from
      chemotherapy, permitting in up to 50% of these cases a curative resection. The
      case is reported of a 18-year-old man with bilateral gynecomastia secondary to an
      unknown hepatic fibrolamellar carcinoma producing oestrogens. Serum alpha
      fetoprotein was negative; des-gamma-carboxy prothrombin (DCP) level was elevated.
      CT scan and MRI showed a solid hepatic tumour (theta 10 cm) without evidence of
      extrahepatic spreading. By a needle biopsy a fibrolamellar carcinoma was
      diagnosed. On March 1995 a right hemihepatectomy was performed. The postoperative
      course was uneventful and the patient recovered. Specimen's histologic
      examination confirmed the preoperative diagnosis. Intracellular (hepatocytes)
      oestrogens were found, but oestrogen and androgen receptors were negative. After
      surgery DCP and oestradiol levels rapidly decreased and gynaecomastia
      disappeared. A follow-up program was established. On April 2000 a probable
      recurrence within the caudate lobe was discovered by a liver CT scan without
      evidence of extrahepatic spreading. Tumour markers, FNAB, and bone scintigraphy
      were negative. On July 2000 the patient underwent second look laparotomy. Only a
      coeliac lymphadenopathy was found and a lymphadenectomy performed. Specimen's
      histologic examination showed a metastatic lymph nodal disease (FLC). The
      postoperative course was uneventful and the patient recovered. He is currently
      alive without evidence of recurrence 5 years after the second operation.

PMID- 17518333
TI  - Small bowel obstruction by mesh migration after umbilical hernia repair.
AB  - A case of intestinal obstruction due to mesh migration is described. A 61 year
      old patient affected by BPCO and chronic atrial fibrillation is admitted for
      mechanical intestinal obstruction. He underwent a umbilical hernia repair with
      mesh and omphalectomy 6 years before. Laparotomy revealed the obstruction due to
      an inflammatory block including polypropylene mesh penetrating an ileal loop.
      Intestinal resection and mechanical isoperistaltic L-L anastomosis is performed.
      The post-operative period is complicated by cardiorespiratory problems and the
      patient comes discharged in XVII day. The prosthesis migration after umbilical
      hernia repair is an event never described in the literature; instead rare cases
      of migration after inguinal hernia repair are reported. The pathophysiological
      mechanisms of this complication are not still cleared and that makes necessary a
      careful technique in the use of the hernia mesh.

PMID- 17518334
TI  - [Two-stage laparoscopic management of complicated acute diverticulitis. Initial
      experience].
AB  - Today no secure consensus exists about the best treatment of complicated
      diverticulitis. The classic surgical procedures are associated to a high
      immediate and delayed morbidity. In the last few years several more conservative
      techniques have been suggested to allow a later elective resection. Laparoscopic
      exploration, peritoneal lavage, and drain of the abdominal cavity followed by an
      elective sigmoid laparoscopic resection is a new minimal invasive approach. This
      approach has been applied in our unit to treat four patients. All patients had an
      acute abdomen due to complicated diverticulitis and one patient had evidence of
      free air at the abdomen x-ray. At emergent operation pus was cleaned, a
      peritoneal lavage was carried out, a drain was placed near the colonic lesion and
      another one in the pelvis. Patients fully recovered without complication and 2 to
      28 weeks after first operation an elective laparoscopic resection of descending
      and sigmoid colon with a Knight-Griffen colorectal anastomosis was performed.
      Neither residual abscess nor dense adhesions were found at the second operations.
      There were no complications and median hospital stay after the second operation
      was 10 days (range, 8-13 days). Laparoscopic treatment of generalized peritonitis
      due to perforated diverticulitis is an attractive alternative to the traditional
      management of this disease. Our initial results are comparable to that published
      in the literature. This approach can be safe and effective in selected cases of
      complicated acute diverticulitis.

PMID- 17518335
TI  - Hemoperitoneum after percutaneous liver biopsy. Video-laparoscopic management.
AB  - BACKGROUND: Percutaneous liver biopsy is a safe procedure, with a low rate of
      major complications. Among these massive hemoperitoneum is the most life
      threatening, and its management sometimes leads to an emergency invasive surgical
      approach. CASE REPORT AND RESULTS: The following case highlights the possible
      role of laparoscopy in diagnosis and treatment of this condition. In this patient
      a significant intraperitoneal bleeding developed from a liver lesion 48 hours
      after needle-biopsy. Video-laparoscopic exploration evidenced a grade III
      laceration of the right lobe, successfully managed with coagulation and
      apposition of an absorbable haemostatic gauze. Peritoneal toilette and multiple
      drains completed the procedure. No surgical complications developed and the
      patient was discharged on 5th post-operative day. DISCUSSION: Minimally invasive
      surgery has been, in this case, an adequate alternative for the treatment of this
      bleeding complication of liver biopsy, offering advantages in terms of low
      morbidity, quick recovery and satisfying cosmetic results. CONCLUSIONS:
      Laparoscopy is gaining a prominent role in penetrating liver trauma, whenever
      conservative or angiographic management fails, and should be considered as the
      first surgical attempt especially in patients with stable hemodynamics despite
      active intraperitoneal bleeding.

PMID- 17518336
TI  - Very atypical presentation of a retroperitoneal "atypical lipoma". A well
      differentiated liposarcoma presenting as sciatic hernia.
AB  - Unlike hernias and neoplasms of any other body site, the sciatic hernia is
      uncommon and the finding of an atypical lipoma in it is probably unique. In such
      instance making the correct diagnosis is paramount in order to perform a
      procedure with a radical intent. A CT scan must be considered any time a rare
      form of hernia is observed and the surgical treatment of a retroperitoneal lipoma
      has to be radical, to prevent a recurrence. This is the strategy followed by the
      authors in a case of a 53 year old lady presenting with a large retroperitoneal
      lipomatous neoplasm within a sciatic hernia.

PMID- 17518337
TI  - [Thyreopathy associated with vagus schwannoma].
AB  - We report the case of a young woman who underwent total thyroidectomy for a
      suspect nodular thyreopathy and occasionally happened to be affected
      simultaneously by vagus nerve schwannoma. Symptomatology is discussed and we
      propose a review of the literature about this non frequent pathology and discuss
      the latest diagnostic procedures and surgical indications and treatment.

PMID- 17518338
TI  - Inhibition of farnesyltransferase: a rational approach to treat cancer?
AB  - This article presents in brief the development of farnesyltransferase inhibitors
      (FTIs) and their preclinical and clinical status. In this review the mechanism of
      action of FTIs is discussed and their selectivity issue towards tumor cells is
      also addressed. The significant efficacy of FTIs as single or combined agents in
      preclinical studies stands in contrast with only moderate effects in Clinical
      Phase II-III studies. This suggests that there is a need to further explore and
      understand the complex mechanism of action of FTIs and their interaction with
      cytotoxic agents.

PMID- 17518339
TI  - Quantifying the inactivation rate constants for the molecular species comprising
      the catalytic cycle of Leuconostoc mesenteroides glucose 6-phosphate
      dehydrogenase.
AB  - When an unstable enzyme is incubated with its substrate(s), catalysis may cease
      before chemical equilibrium is attained. The residual substrate concentrations
      depend on their initial concentrations, the initial enzymic activity, and the
      inactivation rate constants for each molecular species that comprise the
      catalytic cycle. The underlying theory has been elaborated previously for single
      substrate reactions and here it is extended to bi-substrate reactions. The theory
      is illustrated by application to glucose 6-phosphate dehydrogenase, which is
      unstable when exposed to a low concentration of sodium dodecyl sulphate. It is
      shown that the ternary complex containing both substrates is resistant to
      inactivation while each of the remaining complexes undergoes first-order decay.
      Rate constants for the inactivation of each complex are calculated.

PMID- 17518340
TI  - Kinetic analysis of a general model of activation of aspartic proteinase zymogens
      involving a reversible inhibitor. I. Kinetic analysis.
AB  - Starting from a simple general reaction mechanism of activation of aspartic
      proteinases zymogens involving a uni- and a bimolecular simultaneous activation
      route and a reversible inhibition step, the time course equation of the zymogen,
      inhibitor and activated enzyme concentrations have been derived. Likewise,
      expressions for the time required for any reaction progress and the corresponding
      mean activation rates as well as the half-life of the global zymogen activation
      have been derived. An experimental design and kinetic data analysis is suggested
      to estimate the kinetic parameters involved in the reaction mechanism proposed.

PMID- 17518341
TI  - Kinetic analysis of a general model of activation of aspartic proteinase zymogens
      involving a reversible inhibitor. II. Contribution of the uni- and bimolecular
      activation routes.
AB  - From the kinetic study carried out in part I of this series (preceding article)
      an analysis quantifying the relative contribution to the global process of the
      uni- and bimolecular routes has been carried out. This analysis suggests a way to
      predict the time course of the relative contribution as well as the effect on
      this relative weight of the initial zymogen, inhibitor and activating enzyme
      concentrations.

PMID- 17518342
TI  - Quantitative structure-activity relationship study of human A3 adenosine receptor
      antagonists: derivatives of 2-aryl-1,2,4-triazolo [4,3-alpha]quinoxaline.
AB  - A quantitative structure-activity relationship (QSAR) study was conducted on the
      antagonistic activities of derivatives of 2-aryl-1,2,4-triazolo[4,3
      alpha]quinoxaline at the human A3 adenosine receptor. As per the structural
      framework, the title analogues were subdivided into two congeneric series, namely
      the 1,4-dione and the 4-amino-1-one series. A majority of substituents occurred
      at the R- and a limited number at the X-positions in both of these series. In the
      case of the 1,4-dione series, the derived significant QSAR equation revealed that
      those substituents exhibiting a larger field effect at R renders the molecule to
      more efficiently bind at the receptor site. The study also extrapolated the
      requirement of electron-donor substituents at the X-position which, at present,
      is regarded as insensitive to any interaction due to limited substitution.
      However, the X-position may be explored in a further synthetic study. From the
      derived correlation equation for the 4-amino-1-one series, it appeared that a
      strong electron-withdrawing substituent at R will enhance the pK(i) value of a
      compound while a strong electron-donor at this position will have a detrimental
      effect on it. Based on correlation equations, derived using different electronic
      parameters, it may be interpreted that the two series of compounds attain
      different orientation inside the recognition site of the receptor.

PMID- 17518343
TI  - Synthesis and antibacterial activity of some 5-(4-biphenylyl)-7-aryl [3,4-d]
      1,2,3-benzoselenadiazoles.
AB  - A new series of 5-(4-biphenylyl)-7-aryl[3,4-d]-1,2,3-benzoselenadiazoles were
      prepared, characterized by elemental analysis, 1H NMR and 13C NMR spectral
      studies, and tested for antibacterial activities. The compounds were very
      effective against the tested Gram-positive bacteria; 7b was the most effective
      compound.

PMID- 17518344
TI  - Template synthesis, spectroscopic studies and biological activities of
      macrocyclic complexes derived from thiocarbohydrazide and glyoxal.
AB  - A novel series of complexes of the type [M(TML)X2]; where TML is Tetradentate
      Macrocyclic Ligand; M = Co(II), Ni(II), Cu(II), Zn(II)or Cd(II); X = Cl-, CH3COO-
      or NO3- have been synthesized by template condensation of glyoxal and
      thiocarbohydrazide in the presence of divalent metal salts in methanolic medium.
      The complexes have been characterized by elemental analyses, conductance
      measurements, molecular weight determination, magnetic measurements, electronic,
      NMR, infrared and far infrared spectral studies. Electronic spectra along with
      magnetic moments suggest a six coordinate octahedral geometry for these
      complexes. The low molar conductance values indicates them to be non
      electrolytes. The biological activities of the metal complexes have been tested
      in vitro against a number of pathogenic bacteria to assess their inhibitory
      potential.

PMID- 17518345
TI  - Antitubercular activity of novel substituted 4,5-dihydro-1H-1
      pyrazolylmethanethiones.
AB  - A series of, anilino-5-(substituted) phenyl-3-(4-hydroxy-3-methylphenyl)-4,5
      dihydro-1H-1-pyrazolylmethanethione and 2-chloroanilino-5-(substituted) phenyl-3
      (4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolylmethanethione were
      synthesized by the reaction between hydrazine hydrate and the chalcones (3a-k)
      followed by condensation with the appropriate aryl isothiocyanate which yielded
      the N-substituted pyrazoline derivatives. These were tested for their in-vitro
      anti-mycobacterial activity against INH resistant Mycobacterium tuberculosis
      (INHR MTB) using the BACTEC 460 radiometric system. Compound 2-chloroanilino-5
      (2,6-dichlorophenyl)-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolyl
      methanethione (6i) was found to be most active agent with a minimum inhibitory
      concentration of 0.96 microg/mL.

PMID- 17518346
TI  - Mechanistic studies of electrophilic protease inhibitors of full length hepatic C
      virus (HCV) NS3.
AB  - The inhibition mechanism of electrophilic peptide-based protease inhibitors of
      full-length hepatitis C virus (HCV) NS3 has been investigated by determining the
      K(i)-values for a series of compounds differing in the electrophilicity and
      acidity of the C-terminal residue at pH-values above and below the pK(a) of the
      catalytic histidine (6.85) and at two different ionic strengths. Electrophilic
      compounds with a pentafluoroethyl ketone group showed stronger inhibition at pH 8
      than pH 6, as expected for a mechanism requiring an unprotonated catalytic
      histidine. However, the difference was only significant at high ionic strength.
      In contrast, electrophilic compounds with an acidic C-terminal group or a cyclic
      P1 residue showed a lower inhibitory effect at pH 8 than at pH 6, inconsistent
      with a mechanism-based inhibition. Moreover, all electrophilic compounds had an
      unexpectedly strong inhibition at pH 6, when mechanism-based inhibition is
      unlikely. The results suggest that for some of the electrophilic compounds the
      reactive group may not be properly positioned in the active site and that binding
      of these inhibitors is a result of non-covalent interactions. The nature of these
      interactions is discussed.

PMID- 17518347
TI  - Chemical synthesis and in vitro biological evaluation of a phosphorylated
      bisubstrate inhibitor of type 3 17beta-hydroxysteroid dehydrogenase.
AB  - Type 3 17beta-hydroxysteroid dehydrogenase (17beta-HSD) catalyzes the last step
      in the biosynthesis of the potent androgen testosterone (T) by selectively
      reducing the C17 ketone of 4-androstene-3,17-dione (delta4-dione), with NADPH as
      cofactor. This enzyme is thus an interesting therapeutic target for androgen
      sensitive diseases. Using an efficient convergent chemical approach we
      synthesized a phosphorylated version of the best delta4-dione/adenosine hybrid
      inhibitor of type 3 17beta-HSD previously reported. An appropriately protected
      C2' phosphorylated adenosine was first prepared and linked by esterification to
      the steroid delta4-dione bearing an alkyl spacer. After three deprotection steps,
      the phosphorylated bisubstrate inhibitor was obtained. The inhibitory potency of
      this compound was evaluated on homogenated HEK-293 cells overexpressing type 3
      17beta-HSD and compared to the best non-phosphorylated bisubstrate inhibitor.
      Unexpectedly, the phosphorylated derivative was slightly less potent than the non
      phosphorylated bisubstrate inhibitor of type 3 17beta-HSD. Two hypotheses are
      discussed to explain this result: 1) the phosphorylated adenosine moiety does not
      interact optimally with the cofactor-binding site and 2) the bisubstrate
      inhibitors, phosphorylated or not, interact only with the substrate-binding site
      of type 3 17beta-HSD.

PMID- 17518348
TI  - The effects of captopril and losartan on erythrocyte membrane Na+/K(+)-ATPase
      activity in experimental diabetes mellitus.
AB  - Diabetes mellitus induces a decrease in sodium potassium-adenosine triphosphatase
      (Na+/K(+)-ATPase) activity in several tissues in the rat and red blood cells
      (RBC) and nervous tissue in human patients. This decrease in Na+/K(+)-ATPase
      activity is thought to play a role in the development of long-term complications
      of the disease. Angiotensin enzyme inhibitors (ACEi) and angiotensin-II receptor
      antagonists (ARBs) reduce proteinuria and retard the progression of renal failure
      in patients with IDDM and diabetic rats. We investigated the effects of captopril
      and losartan, which are used in the treatment of diabetic nephropathy, on
      Na+/K(+)-ATPase activity. Captopril had an inhibitory effect on red cell plasma
      membrane Na+/K+ ATPase activity, but losartan did not. Our study draws attention
      to the inhibitory effect of captopril on Na+/K+ ATPase activity. Micro and macro
      vascular complications are preceeding mortality and morbidity causes in diabetes
      mellitus. There is a strong relationship between the decrease in Na+/K+ ATPase
      activity and hypertension. The non-sulphydryl containing ACEi and ARBs must be
      the choice of treatment in hypertensive diabetic patients and diabetic
      nephropathy.

PMID- 17518349
TI  - Evalution of toxicity of abcisic acid and gibberellic acid in rats: 50 days
      drinking water study.
AB  - In the present study, the influence of subchronic effects of two plant growth
      regulators (PGRs) [Abcisic acid (ABA) and Gibberellic acid (GA3)] on antioxidant
      defense systems [reduced glutathione (GSH), glutathione reductase (GR),
      superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)]
      and lipid peroxidation level (malondialdehyde = MDA) in various tissues of the
      rat were investigated during treatment as a drinking water model. 75 ppm of ABA
      and GA3 in drinking water were continuously administered orally to rats (Sprague
      Dawley albino) ad libitum for 50 days. The PGRs treatments caused different
      effects on the antioxidant defense systems and MDA content of dosed rats compared
      to controls. The lipid peroxidation end product MDA significantly increased in
      the lungs, heart and kidney of rats treated with GA3 without significant change
      in the spleen. ABA caused also a significant increase in MDA content in the
      spleen, lungs, heart and kidney. The GSH levels were significantly depleted in
      the spleen, lungs and stomach of rats treated with ABA without any change in the
      tissues of rats treated with GA3 except the kidney where it increased.
      Antioxidant enzyme activities such as SOD significantly increased in the lungs
      and stomach and decreased in the spleen and heart tissues of rats treated with
      GA3. Meanwhile, SOD significantly decreased in the spleen, heart and kidney and
      increased in the lungs of rats treated with ABA. While CAT activity significantly
      decreased in the lungs of rats treated with GA3, a significant increase occurred
      in the heart of rats treated with both PGRs. On the other hand, the ancillary
      enzyme GR activity in the tissues were either significantly depleted or not
      changed with PGRs treatment. The drug metabolizing enzyme GST activity
      significantly decreased in the lungs of rats treated with ABA but increased in
      the stomach of rats treated with both PGRs. As a conclusion, the rats resisted
      oxidative stress via the antioxidant mechanism. But the antioxidant mechanism
      could not prevent the increases in lipid peroxidation in rat's tissues. This
      data, along with changes, suggests that PGRs produced substantial systemic organ
      toxicity in the spleen, lungs, stomach, heart and kidney during a 50-day period
      of subchronic exposure.

PMID- 17518350
TI  - In vitro and in vivo trypanocidal activity of the ethyl esters of N-allyl and N
      propyl oxamates using different Trypanosoma cruzi strains.
AB  - The trypanocidal activity of N-allyl (NAOx) and N-propyl (NPOx) oxamates and that
      of the ethyl esters ofN-allyl (Et-NAOx) and N-propyl (Et-NPOx) oxamates were
      tested on cultured epimastigotes (in vitro) and murine trypanosomiasis (in vivo)
      using five different T. cruzi strains. NAOx and NPOx did not penetrate intact
      epimastigotes and therefore we were not able to detect any trypanocidal effect
      with these oxamates. Whereas the ethyl esters (Et-NAOx and Et-NPOx), acting as
      prodrugs, exhibited in vitro and in vivo trypanocidal activity on the five tested
      T. cruzi strains. On the contrary, when Nifurtimox and Benznidazole used as
      reference drugs were tested, we found that only three of the five tested T cruzi
      strains were affected, whereas the other two strains, Miguz and Compostela, were
      resistant to the in vitro and in vivo trypanocidal activity of these compounds.

PMID- 17518351
TI  - Enzyme inhibition activities of Andrachne cardifolia Muell.
AB  - The crude methanolic extract and various fractions of Andrachne cardifolia Muell,
      including chloroform, ethyl acetate and n-butanol fractions were subjected to in
      vitro enzyme inhibition activity against acetylcholinesterase,
      butyrylcholinesterase, lipoxygenase and urease enzymes. A significant enzyme
      inhibition activity (40-89%) was shown by the crude methanolic extract and its
      fractions against lipoxygenase, while low to significant activity (40-71%)
      against butyrylcholinesterase. The crude methanolic extract and its various
      fractions demonstrated poor to significant activity (25-73%) against
      acetylcholinesterase and no activity against urease.

PMID- 17518352
TI  - The inhibitory effect of some new synthesized xanthates on mushroom tyrosinase
      activities.
AB  - Three iso-alkyldithiocarbonates (xanthates), as sodium salts, C3H7OCS2Na (I),
      C4H9OCS2Na (II) and C5H11OCS2Na (III), were synthesized, by the reaction between
      CS2 with the corresponding iso-alcohol in the presence of NaOH, and examined for
      inhibition of both cresolase and catecholase activities of mushroom tyrosinase
      (MT) from a commercial source of Agricus bisporus. 4-[(4-methylbenzo)azo]-1,2
      benzendiol (MeBACat) and 4-[(4-methylphenyl)azo]-phenol (MePAPh) were used as
      synthetic substrates for the enzyme for the catecholase and cresolase reactions,
      respectively. Lineweaver-Burk plots showed different patterns of mixed and
      competitive inhibition for the three xanthates and also for cresolase and
      catecholase activities of MT. For cresolase activity, I and II showed a mixed
      inhibition pattern but III showed a competitive inhibition pattern. For
      catecholase activity, I showed mixed inhibition but II and III showed competitive
      inhibition. These new synthesized compounds are potent inhibitors of MT with K(i)
      values of 9.8, 7.2 and 6.1 microM for cresolase inhibitory activity, and also
      12.9, 21.8 and 42.2 microM for catecholase inhibitory activity for I, II and III,
      respectively. They showed a greater inhibitory potency towards the cresolase
      activity of MT. Both substrate and inhibitor can be bound to the enzyme with
      negative cooperativity between the binding sites (alpha > 1) and this negative
      cooperativity increases with increasing length of the aliphatic tail in these
      compounds in both cresolase and catecholase activities. The cresolase inhibition
      is related to the chelating of the copper ions at the active site by a negative
      head group (S-) of the anion xanthate, which leads to similar values of K(i) for
      all three xanthates. Different K(i) values for catecholase inhibition are related
      to different interactions of the aliphatic chains of I, II and III with
      hydrophobic pockets in the active site of the enzyme.

PMID- 17518353
TI  - Production and chitinase-binding ability of lipo-chitopentaose nodulation factor.
AB  - The penta-N-acetyl-chitopentaose 2 has been prepared by using recombinant E. coli
      strains harboring the nodC gene (encoding chitooligosaccharide synthase) from
      Azorhizobium caulinodans. Then, the deacetylase NodB removed the N-acetyl moiety
      from the nonreducing terminus of 2 to give tetra-N-acetyl-chitopentaose 3. N
      Acylation of 3 with stearyl chloride was performed in DMF containing water and
      provided the corresponding lipo-chitopentaose nodulation factor 4. A binding
      chitinase assay indicated that 4 was much more stable than 3.

PMID- 17518354
TI  - The prevalence and risk factors of post-inflammatory hyperpigmentation after
      fractional resurfacing in Asians.
AB  - BACKGROUND: Ablative laser resurfacing is considered to be the main therapeutic
      option for the treatment of wrinkles and acne scarring. However, in Asians, post
      inflammatory hyperpigmentation (PIH) is a common adverse effect of laser
      resurfacing. Fractional resurfacing is a new concept of skin rejuvenation whereby
      zones of micro thermal injury are generated in the skin with the use of a 1,540
      nm laser. The risk and prevalence of hyperpigmentation in dark-skinned patients
      using this approach have not been studied. OBJECTIVE: To assess the prevalence
      and risk factors of PIH that is associated with the use of fractional resurfacing
      in Asians. METHOD: A retrospective study of 37 Chinese patients who were treated
      with fractional resurfacing for acne scarring, skin rejuvenation, and
      pigmentation was carried out. In all of the cases, pre- and post-treatment
      clinical photographs (from standardized and cross-polarized views) were taken
      using the Canfield CR system. Two independent observers assessed the photographs.
      A prospective study of treatments of nine different density and energy levels
      that were applied to the forearms of 18 volunteers was also performed. Clinical
      photographs were assessed pre- and post-treatment for evidence of PIH. RESULT: In
      the retrospective study, 119 treatment sessions were performed. Sixty-eight
      treatment sessions were high energy, low density; 51 sessions were low energy,
      high density. Patients who underwent a high energy but low-density treatment
      (range of energy 7-20 mJ; average energy 16.3 mJ, 1,000 MTZ) were associated with
      a lower prevalence of generalized PIH (7.1% vs. 12.4%) than those who underwent a
      low energy but high-density (range of energy 6-12 mJ; average energy 8.2 mJ,
      2,000 MTZ) treatment. However, the difference was not statistically significant.
      Localized PIH occurred in the peri-oral area among patients who did not receive
      air cooling as an adjunctive therapy. CONCLUSION: Both the density and energy of
      the treatment determines the risk of PIH in dark-skinned patients. Density may be
      of more important but further studies are necessary to determine this. Cooling to
      prevent bulk tissue heating is also important, especially in small anatomical
      areas. By using adequate parameters, the risk of PIH in dark-skinned patients can
      be significantly reduced.

PMID- 17518355
TI  - Critical assessment of inverse gas chromatography as means of assessing surface
      free energy and acid-base interaction of pharmaceutical powders.
AB  - Inverse gas chromatography (IGC) has been employed as a research tool for
      decades. Despite this record of use and proven utility in a variety of
      applications, the technique is not routinely used in pharmaceutical research. In
      other fields the technique has flourished. IGC is experimentally relatively
      straightforward, but analysis requires that certain theoretical assumptions are
      satisfied. The assumptions made to acquire some of the recently reported data are
      somewhat modified compared to initial reports. Most publications in the
      pharmaceutical literature have made use of a simplified equation for the
      determination of acid/base surface properties resulting in parameter values that
      are inconsistent with prior methods. In comparing the surface properties of
      different batches of alpha-lactose monohydrate, new data has been generated and
      compared with literature to allow critical analysis of the theoretical
      assumptions and their importance to the interpretation of the data. The commonly
      used (simplified) approach was compared with the more rigorous approach
      originally outlined in the surface chemistry literature.

PMID- 17518356
TI  - Interactions of azole antifungal agents with the human breast cancer resistance
      protein (BCRP).
AB  - Breast cancer resistance protein (BCRP) is an efflux transporter that plays an
      important role in drug disposition. The goal of this study was to investigate the
      interactions of azole antifungal agents, ketoconazole, itraconazole, fluconazole,
      and voriconazole, with BCRP. First, the effect of the azoles on BCRP efflux
      activity in BCRP-overexpressing HEK cells was determined by measuring
      intracellular pheophorbide A (PhA) fluorescence using flow cytometry. We found
      that keotoconazole and itraconazole significantly inhibited BCRP-mediated efflux
      of PhA at low microM concentrations. However, fluconazole only mildly inhibited
      and voriconazole did not inhibit BCRP efflux activity at concentrations up to 100
      microM. The IC(50) value of ketoconazole for inhibition of BCRP-mediated PhA
      efflux was 15.3 +/- 6.5 microM. Ketoconazole and itraconazole also effectively
      reversed BCRP-mediated resistance of HEK cells to topotecan. When direct efflux
      of [(3)H]ketoconazole was measured in BCRP-overexpressing HEK cells, we found
      that [(3)H]ketoconazole was not transported by BCRP. Consistent with this
      finding, BCRP did not confer resistance to ketoconazole and itraconazole in HEK
      cells. Taken together, ketoconazole and itraconazole are BCRP inhibitors, but
      fluconazole and voriconazole are not. These results suggest that BCRP could play
      a significant role in the pharmacokinetic interactions of ketoconazole or
      itraconazole with BCRP substrate drugs.

PMID- 17518357
TI  - Combined use of crystalline salt forms and precipitation inhibitors to improve
      oral absorption of celecoxib from solid oral formulations.
AB  - Biopharmaceutical evaluation of crystalline celecoxib salts in novel solid
      formulations, which were designed to simultaneously facilitate dissolution and
      inhibit precipitation in vitro, showed fast and complete absorption in beagle
      dogs at doses up to 7.5 mg/kg orally. In contrast, 5 mg/kg celecoxib in the form
      of Celebrex(R) showed approximately 40% absolute bioavailability in a cross-over
      experiment. An in vitro-in vivo correlation was observed in dog, and a threshold
      level of in vitro dissolution needed to maximize in vivo performance was
      highlighted. Oral bioavailability was limited in the absence of excipient
      combinations that delayed precipitation of celecoxib free acid as the salt
      neutralized in the GI fluid. Formulations of crystal forms having high energy (a
      'spring'), thus transiently increasing solubility in aqueous solution relative to
      the free acid, combined with excipients functioning as precipitation inhibitors
      ('parachutes') were shown to provide both enhanced dissolution and high oral
      bioavailability.

PMID- 17518358
TI  - The role of the cyclic imide in alternate degradation pathways for asparagine
      containing peptides and proteins.
AB  - Peptides and proteins exhibit enhanced reactivity at asparagine residues due to
      the formation of a reactive succinimide intermediate that produces normal and
      isoaspartyl deamidation products along with significant racemization. This study
      examines the potential for attack of amine nucleophiles at the succinimide
      carbonyls to generate alternate decomposition products, depending on the
      nucleophile involved in the reaction. The reactions of the model peptides Phe-Asn
      Gly (FNG) and Phe-isoAsn-Gly (FisoNG) were explored as a function of pH (8.5
      10.5) in the presence and absence of ammonia buffer (0.2-2 M) using an isocratic
      HPLC method to monitor reactant disappearance and product formation. In addition
      to deamidation to form isoAsp and Asp peptides, two additional types of reactions
      were found to occur via the succinimide intermediate under these conditions. Back
      reaction of the succinimide with ammonia led to peptide backbone isomerization
      while intramolecular attack by the amino terminus produced diketopiperazines. A
      kinetic model assuming a central role for the succinimide intermediate was
      derived to fit the concentration versus time data. These studies implicate the
      cyclic imide as a key intermediate in the formation of alternate peptide and
      protein degradants, including possible covalent amide-linked aggregates that may
      form from intermolecular attack of the cyclic imide by neighboring amino groups.

PMID- 17518359
TI  - Effects of solution conditions and surface chemistry on the adsorption of three
      recombinant botulinum neurotoxin antigens to aluminum salt adjuvants.
AB  - Botulinum neurotoxin (BoNT) is a biological warfare threat. Protein antigens have
      been developed against the seven major BoNT serotypes for the development of a
      recombinant protein vaccine. This study is an evaluation of adsorption profiles
      for three of the recombinant protein antigens to aluminum salt adjuvants in the
      development of a trivalent vaccine against BoNT. Adsorption profiles were
      obtained over a range of protein concentrations. The results document that charge
      charge interactions dominate the adsorption of antigen to adjuvant. Optimal
      conditions for adsorption were determined. However, potency studies and solution
      stability studies indicated the necessity of using aluminum hydroxide adjuvant at
      low pH. To improve the adsorption profiles to AlOH adjuvant, phosphate ions were
      introduced into the adsorption buffers. The resulting change in the adjuvant
      chemistry led to an improvement of adsorption of the BoNT antigens to aluminum
      hydroxide adjuvant while maintaining potency. Competitive adsorption profiles
      were also determined, and showed changes in maximum adsorption from mixed
      solutions compared to adsorption from individual protein solutions. The
      adsorption profiles for each protein varied due to differences in adsorption
      mechanism and affinity for the adjuvant surface. These results emphasize the
      importance of evaluating competitive adsorption in the development of multivalent
      vaccine products.

PMID- 17518360
TI  - Potency of siRNA versus shRNA mediated knockdown in vivo.
AB  - The intracellular delivery of small interfering RNA (siRNA) is a therapeutic
      strategy to transiently block gene expression. Two silencing RNA strategies
      utilize either synthetic double stranded RNA or plasmid DNA encoding a short
      hairpin RNA (shRNA). In the present study, we have quantitatively compared the
      potency of siRNA (siLuc1) and shRNA (pShagLuc) mediated knockdown of luciferase
      expression in vivo using hydrodynamic dosing and bioluminescence imaging (BLI).
      Following hydrodynamic coadministration of siLuc1 or pShagLuc with a plasmid
      encoding luciferase (pGL3), mice were analyzed for transgene expression by BLI.
      The knockdown of luciferase expression by siLuc1 or pShagLuc was observed at 3 h
      and persisted for 3 days. The potency of siLuc1 and pShagLuc was equivalent with
      maximal effect at 10 microg coadministered with 1 microg of pGL3 resulting in
      >80% knockdown. Combined dosing of siLuc1 and pShagluc (5 microg each) with 1
      microg of pGL3 resulted in >99% knockdown. Analysis of the data established that
      shRNA was significantly more potent than siRNA at mediating knockdown when
      compared on a mole basis. The combination of hydrodynamic dosing and BLI to
      measure siRNA or shRNA mediated knockdown of luciferase provide an attractive in
      vivo quantitative method to test formulations that target the liver.

PMID- 17518361
TI  - Characterization and selective crystallization of famotidine polymorphs.
AB  - Famotidine crystallizes in two different polymorphic forms: the metastable
      polymorph B and the stable polymorph A. In this work, solid characterization for
      both polymorphs has been conducted in detail. The solubility, metastable zone
      width and interfacial energy of both polymorphs in different solvents have been
      measured. The influence of solvent, cooling rate, initial concentration and the
      temperature of nucleation on polymorphism has been investigated. Results show
      that the nature of polymorph that crystallizes from solution depends on the
      initial concentration of the solution, solvent, cooling rate, and the temperature
      of nucleation. Polymorph B preferentially crystallizes only at high
      concentrations. When acetonitrile or methanol is used as solvent, cooling rate
      can affect the polymorph of product only at high concentrations. While water is
      used as solvent, cooling rate has no effect on the polymorph of product, and
      nucleation temperature is found to be the predominant controlling factor. The
      effect of crystallization conditions on the polymorph of famotidine can be mainly
      attributed to the conformational polymorphism. Finally the "polymorphic window"
      for famotidine crystallized from aqueous solution has been described.

PMID- 17518362
TI  - The structure, stability, and complex behavior of recombinant human gelatins.
AB  - Gelatin prepared from animal sources is widely used as a stabilizer in vaccine
      formulations. The disadvantages associated with their use such as heterogeneity
      and allerginicity, have led to the development of recombinant human gelatins
      (rhGs) as a substitute. This study focuses on characterizing the structure and
      monitoring the physical stability of four molecular weights ( approximately 8.5,
      25, 50, and 100 kDa) of rhGs as a function of temperature and pH. The information
      supplied should be useful in predicting the behavior of rhGs under formulation
      conditions. A number of spectroscopic techniques were employed in this study.
      Experimental results indicated that the solution properties of all four rhGs were
      unpredictable with micro-aggregation observed at various pH values. The 8.5 kDa
      rhG was found to be in a micro-aggregated state at pH 5 while the 25 kDa rhG was
      found to be more aggregated at pHs 5, 7, and 8. The properties of these
      aggregates have been analyzed as a function of temperature. The rhGs were also
      found to complex with the polyanion heparin through electrostatic and
      nonelectrostatic interactions. The stability of these complexes has been studied
      as a function of temperature and pH.

PMID- 17518363
TI  - Bisphosphonate action: revelations and deceptions from in vitro studies.
AB  - Bisphosphonates (BPs) are a class of drugs used in the treatment of osteoporosis
      and diseases of high bone turnover, as well as for control of skeletal related
      events secondary to malignant disease. The key to BP specificity is their
      capacity to bind rapidly and with high affinity to bone surfaces. The cellular
      targets of BPs at the bone surface have been a source of controversy. In addition
      to osteoclasts, it has been frequently proposed that BPs may affect a variety of
      cell types including osteoclast precursors, osteoblasts and bone-lining cells,
      immunogenic cells, and tumour cells. However, there is an emerging body of
      literature from in vitro studies indicating that BPs are only released and taken
      up from bone surfaces by resorbing osteoclasts. In this scenario, the only
      significant exposure of non-resorbing cells to BP would occur during the initial
      period after dosing, prior to drug clearance from the soft tissues. Auspiciously,
      several groups have reported on revised culture systems that better reflect the
      pharmacology of BP dosing.

PMID- 17518364
TI  - CYP2D6 polymorphisms and the impact on tamoxifen therapy.
AB  - The cytochrome P450 2D6 (CYP2D6) is an enzyme known to metabolize a variety of
      xenobiotics and drugs. Inter-individual variation in the metabolic capacity of
      this enzyme has been extensively studied and associations with genotype have been
      established. Genetic polymorphisms have been grouped as nonfunctional, reduced
      function, functional, and multiplication alleles phenotypically. Individuals
      carrying these alleles are presumed to correspond to poor, intermediate,
      extensive, and ultrarapid metabolizers (UM), respectively. Tamoxifen has been
      shown to be metabolized by CYP2D6 to the more potent metabolite endoxifen. Poor
      metabolizers (PM) of tamoxifen have lower levels of endoxifen and poorer clinical
      outcomes as compared to extensive metabolizers (EM). Here, we will provide an
      overview of the history and application of CYP2D6 pharmacogenetics, and will
      discuss the clinical implications of recent developments relating to the
      involvement of CYP2D6 in tamoxifen treatment.

PMID- 17518365
TI  - Enzybiotics: a look to the future, recalling the past.
AB  - The discovery and development of antibiotics was one of the greatest successes of
      Medicine in the 20th century and allowed the control of many diseases caused by
      microorganisms. Nevertheless, it is necessary to search constantly for new
      therapeutic tools in the continuing fight against disease-causing microorganisms
      and this probably leads us to today's concept of enzybiotics. Although
      microorganism-degrading enzymes have been known since the beginning of the last
      century, their use was soon forgotten because of the widespread use of
      antibiotics. The term enzybiotic is a hybrid word from "enzyme" and "antibiotic"
      and refers to phages: that is, viruses that attack and lyse bacteria and that can
      potentially help us to fight bacterial diseases. If the concept of enzybiotic is
      extended to antifungal enzymes, an enormous potential in the struggle against
      microorganism-due diseases may become available in the foreseeable future.

PMID- 17518366
TI  - Molecular aspects of phytoestrogen selective binding at estrogen receptors.
AB  - Phytoestrogens are a diverse group of plant-derived compounds that structurally
      or functionally mimic mammalian estrogens and show potential benefits for human
      health. An increase in phytoestrogen research over the past few decades has
      demonstrated the biological complexity of phytoestrogens, which belong to several
      different chemical classes and act through diverse mechanisms. Identification of
      the estrogen receptor beta (ERbeta) and research into various ligand classes has
      enabled elucidation of molecular aspects important in selective ER binding. This
      article explores the structural characteristics and significance of functional
      groups as they relate to phytoestrogen selectivity for ER binding.

PMID- 17518367
TI  - The Lille model: a new tool for therapeutic strategy in patients with severe
      alcoholic hepatitis treated with steroids.
AB  - Early identification of patients with severe (discriminant function > or = 32)
      alcoholic hepatitis (AH) not responding to corticosteroids is crucial. We
      generated a specific prognostic model (Lille model) to identify candidates early
      on for alternative therapies. Three hundred twenty patients with AH prospectively
      treated by corticosteroids were included in the development cohort and 118 in its
      validation. Baseline data and a change in bilirubin at day 7 were tested. The
      model was generated by logistic regression. The model combining six reproducible
      variables (age, renal insufficiency, albumin, prothrombin time, bilirubin, and
      evolution of bilirubin at day 7) was highly predictive of death at 6 months (P <
      0.000001). The area under the receiver operating characteristic (AUROC) curve of
      the Lille model was 0.89 +/- 0.02, higher than the Child-Pugh (0.62 +/- 0.04, P <
      0.00001) or Maddrey scores (0.66 +/- 0.04, P < 0.00001). In the validation
      cohort, its AUROC was 0.85 +/- 0.04, still higher than the other models,
      including MELD (0.72 +/- 0.05, P = 0.01) and Glasgow scores (0.67 +/- 0.05, P =
      0.0008). Patients above the ideal cutoff of 0.45 showed a marked decrease in 6
      month survival as compared with others: 25% +/- 3.8% versus 85% +/- 2.5%, P <
      0.0001. This cutoff was able to identify approximately 75% of the observed
      deaths. CONCLUSION: In the largest cohort to date of patients with severe AH, we
      demonstrate that the term "nonresponder" can now be extended to patients with a
      Lille score above 0.45, which corresponds to 40% of cases. Early identification
      of subjects with substantial risk of death according to the Lille model will
      improve management of patients suffering from severe AH and will aid in the
      design of future studies for alternative therapies.

PMID- 17518368
TI  - Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic
      steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is now the most frequent cause of chronic
      liver impairment in developed countries and is a suggested causative factor in
      the development of cryptogenic cirrhosis and hepatocellular carcinoma. At present
      there is no effective and accepted therapy for NASH. The renin-angiotensin system
      is involved in hepatic fibrosis through activation of hepatic stellate cells,
      major fibrogenic cells in the liver. Hepatic stellate cells are activated by
      liver injury to express excessive matrix proteins and profibrogenic cytokines
      such as transforming growth factor-beta 1. Medicines that inhibit this pathway
      may be of therapeutic potential in NASH. Using a methionine-choline-deficient rat
      model of NASH, we studied the potential utility of an angiotensin II type 1
      receptor blocker (ARB), olmesartan, on biochemical, histologic, and antioxidant
      measures of disease activity. ARB significantly attenuated increases in aspartate
      aminotransferase, activation of hepatic stellate cells, oxidative stress,
      expression of transforming growth factor-beta 1, expression of collagen genes,
      and liver fibrosis. CONCLUSION: Our observations strongly suggest a potential
      preventive role for ARB in the progression of nonalcoholic steatohepatitis.

PMID- 17518369
TI  - Identification of host genes involved in hepatitis C virus replication by small
      interfering RNA technology.
AB  - Hepatitis C virus (HCV) replication is highly dependent on host cell factors.
      Identification of these host factors not only facilitates understanding of the
      biology of HCV infection but also enables the discovery of novel targets for anti
      HCV therapy. To identify host genes important for HCV RNA replication, we
      screened a library of small interfering RNA (siRNA) that targets approximately
      4,000 human genes in Huh7-derived EN5-3 cells harboring an HCV subgenomic
      replicon with the nonstructural region NS3-NS5B from the 1b-N strain. Nine
      cellular genes that potentially regulate HCV replication were identified in this
      screen. Silencing of these genes resulted in inhibition of HCV replication by
      more than 60% and exhibited minimal toxicity. Knockdown of host gene expression
      by these siRNAs was confirmed at the RNA level and, in some instances, at the
      protein level. The level of siRNA silencing of these host genes correlated well
      with inhibition of HCV. These genes included those that encoded a G-protein
      coupled receptor (TBXA2R), a membrane protein (LTbeta), an adapter protein
      (TRAF2), 2 transcription factors (RelA and NFkappaB2), 2 protein kinases (MKK7
      and SNARK), and 2 closely related transporter proteins (SLC12A4 and SLC12A5). Of
      interest, some of these genes are members of the tumor necrosis
      factor/lymphotoxin signaling pathway. CONCLUSION: Findings of this study may
      provide important information for understanding HCV replication. In addition,
      these cellular genes may constitute a novel set of targets for HCV antiviral
      therapy.

PMID- 17518370
TI  - The mannose receptor on murine liver sinusoidal endothelial cells is the main
      denatured collagen clearance receptor.
AB  - The purpose of this study was to identify the receptor responsible for
      endocytosis of denatured collagen from blood. The major site of clearance of this
      material (at least 0.5 g/day in humans) is a receptor on liver sinusoidal
      endothelial cells (LSECs). We have now identified an 180-kDa endocytic receptor
      on LSECs, peptide mass fingerprinting of which revealed it to be the mannose
      receptor. Challenge of mannose-receptor knockout mice and their cultured LSECs
      revealed significantly reduced blood clearance and a complete absence of LSEC
      endocytosis of denatured collagen. Organ analysis of wild-type versus knockout
      mice after injection of denatured collagen revealed significantly reduced liver
      uptake in the knockout mice. Clearance/endocytosis of ligands for other receptors
      in these animals was as that for wild-type mice, and denatured collagen uptake in
      wild-type mice was not affected by other ligands of the mannose receptor, namely
      mannose and mannan. Furthermore, unlike that of mannose and mannan, endocytosis
      of denatured collagen by the mannose receptor is calcium independent. This
      suggests that the binding site for denatured collagen is distinct from that for
      mannose/mannan. Mannose receptors on LSECs appear to have less affinity for
      circulating triple helical type I collagen. CONCLUSION: The mannose receptor is
      the main candidate for being the endocytic denatured collagen receptor on LSECs.

PMID- 17518371
TI  - Th2 and regulatory immune reactions are increased in immunoglobin G4-related
      sclerosing pancreatitis and cholangitis.
AB  - Immunoglobin G (IgG) 4-related sclerosing pancreatitis and cholangitis
      (autoimmune pancreato-cholangitis [AIPC]) are recently recognized disease
      entities characterized by high serum IgG4 concentrations and sclerosing
      inflammation with numerous IgG4-positive plasma cells, although the underlining
      immune mechanism remains only speculative. In this study, the immunopathogenesis
      of AIPC was examined with respect to the production of cytokines in situ and the
      possible involvement of regulatory T cells (Tregs) using fresh (5 cases) and
      formalin-fixed (28 cases) specimens of AIPC and related extra-pancreatobiliary
      lesions. Quantitative real-time polymerase chain reaction revealed that AIPC and
      extra-pancreatobiliary lesions had significantly higher ratios of interleukin
      (IL)-4/interferon-gamma (IFN-gamma) (45.8-fold), IL-5/IFN-gamma (18.7-fold), IL
      13/interferon (IFN)-gamma (20.7-fold), IL-10/CD4 (45.3-fold), and tumor growth
      factor (TGF)-beta/CD4 (39.4-fold) than did primary sclerosing cholangitis (PSC)
      and primary biliary cirrhosis (PBC). Lymphocytes with signals for IL-4 and IL-10
      were frequently found in AIPC by in situ hybridization. The expression of Foxp3
      messenger RNA, a transcription factor specific for naturally arising
      CD4(+)CD25(+) Tregs, was significantly increased in AIPC and extra
      pancreatobiliary lesions in comparison to PSC and PBC (36.4-fold).
      Immunohistochemically, CD4(+)CD25(+)Foxp3(+) cells were frequently found in AIPC,
      while few were found in PSC and other disease controls. Taken together, AIPC
      could be characterized by the over-production of T helper (Th) 2 and regulatory
      cytokines. Tregs might be involved in the in situ production of IL-10 and TGF
      beta, which could be followed by IgG4 class switching and fibroplasia.
      CONCLUSION: AIPC is a unique inflammatory disorder characterized by an immune
      reaction predominantly mediated by Th2 cells and Tregs.

PMID- 17518373
TI  - Skills training in telerobotic surgery.
AB  - Surgical robots have the potential to expand the repertoire of minimally invasive
      surgery resulting in more patients benefiting from lower operative morbidity and
      shorter hospital stays. However, in a similar manner to all new surgical
      interventions it necessary to explore the learning curves of practitioners as
      they adopt this new technology to enable optimisation of future training
      programs. Only when the standard of practice is firmly established, should the
      proliferation of robotic practitioners be encouraged thus ensuring patient safety
      is not compromised.

PMID- 17518374
TI  - Robotics in urology: an update.
AB  - Urology has been quick to realise the advantages of surgical robots. We describe
      the main devices currently in use, the advantages and disadvantages of robotic
      assisted surgery and the current and potential urological applications focussing
      on robot-assisted radical prostatectomy.

PMID- 17518375
TI  - Respiration tracking in radiosurgery without fiducials.
AB  - In robotic radiosurgery, a focused beam of radiation is moved by a robot arm. We
      investigated methods for soft-tissue navigation using robotic radiosurgery. In
      previous work we described a method for real-time tracking based on correlation
      between the motion of implanted fiducial markers and external skin markers. In
      this work we extend our method of correlation-based tracking to tracking without
      implanted fiducials. We propose to use deformation algorithms on CT data sets
      combined with registration of digitally reconstructed radiographs and intra
      treatment X-ray images to obtain intermittent information on the target location.
      This information is then combined with our basic correlation method to achieve
      real-time tracking. Our study investigates the feasibility of this approach from
      the point of view of computing time and required level of user interaction. The
      term 7D registration is coined to describe the underlying method for performing
      this task.

PMID- 17518376
TI  - Robotic whole body stereotactic radiosurgery: clinical advantages of the
      Cyberknife integrated system.
AB  - Radiosurgery is defined as the delivery of high doses of ionising radiation, in
      mono- or hypo- fractionated treatments, to destroy tumours or focal areas of
      pathology. The clinical requirements of designing a radiosurgical treatment
      system include providing: a) a highly precise beam delivery to targets located
      throughout the body, b) a highly conformal dose distribution, c) the ability to
      irradiate both small and/or large complex-shaped lesions while minimising the
      dose to adjacent radiosensitive tissues and d) the ability to interactively track
      lesion motion due to normal patient motion. To accomplish this, the CyberKnife
      radiosurgery system has pioneered in this area by taking advantage of the
      inherent geometrical targeting precision of a commercial arm-based robotic system
      carrying a compact X-band linear accelerator and integrated with X-ray imaging
      and visualisation feedback systems. The arm-mounted linear accelerator, equipped
      with patient specific anatomical models, registered to the patient in real-time
      with image guidance, dynamically and safely delivers conformal and homogeneous
      radiation for therapeutic benefit. This paper details the components of the
      CyberKnife system and their integration in the clinical workflow of radiosurgery.

PMID- 17518377
TI  - Precision placement of instruments for minimally invasive procedures using a
      "needle driver" robot.
AB  - Medical practice continues to move toward less invasive procedures. Many of these
      procedures require the precision placement of a needle in the anatomy. Over the
      past several years, our research team has been investigating the use of a robotic
      needle driver to assist the physician in this task. This paper summarizes our
      work in this area. The robotic system is briefly described, followed by a
      description of a clinical trial in spinal nerve blockade. The robot was used
      under joystick control to place a 22 gauge needle in the spines of 10 patients
      using fluoroscopic imaging. The results were equivalent to the current manual
      procedure. We next describe our follow-up clinical application in lung biopsy for
      lung cancer screening under CT fluoroscopy. The system concept is discussed and
      the results of a phantom study are presented. A start-up company named ImageGuide
      has recently been formed to commercialize the robot. Their revised robot design
      is presented, along with plans to install a ceiling-mounted version of the robot
      in the CT fluoroscopy suite at Georgetown University.

PMID- 17518378
TI  - A technical challenge for robot-assisted minimally invasive surgery: precision
      surgery on soft tissue.
AB  - In minimally invasive surgery, a higher degree of accuracy is required by
      surgeons both for current and for future applications. This could be achieved
      using either a manipulator or a robot which would undertake selected tasks during
      surgery. However, a manually-controlled manipulator cannot fully exploit the
      maximum accuracy and feasibility of three-dimensional motion sequences.
      Therefore, apart from being used to perform simple positioning tasks,
      manipulators will probably be replaced by robot systems more and more in the
      future. However, in order to use a robot, accurate, up-to-date and extensive data
      is required which cannot yet be acquired by typical sensors such as CT, MRI, US
      or common x-ray machines. This paper deals with a new sensor and a concept for
      its application in robot-assisted minimally invasive surgery on soft tissue which
      could be a solution for data acquisition in future.

PMID- 17518379
TI  - Haptic interaction in robot-assisted endoscopic surgery: a sensorized end
      effector.
AB  - Conventional endoscopic surgery has some drawbacks that can be addressed by using
      robots. The robotic systems used for surgery are still in their infancy. A major
      deficiency is the lack of haptic feedback to the surgeon. In this paper, the
      benefits of haptic feedback in robot-assisted surgery are discussed. A novel
      robotic end-effector is then described that meets the requirements of endoscopic
      surgery and is sensorized for force/ torque feedback. The endoscopic end-effector
      is capable of non-invasively measuring its interaction with tissue in all the
      degrees of freedom available during endoscopic manipulation. It is also capable
      of remotely actuating a tip and measuring its interaction with the environment
      without using any sensors on the jaws. The sensorized end-effector can be used as
      the last arm of a surgical robot to incorporate haptic feedback and/or to
      evaluate skills and learning curves of residents and surgeons in endoscopic
      surgery.

PMID- 17518380
TI  - A telerobotic haptic system for minimally invasive stereotactic neurosurgery.
AB  - Medical robotics and computer assisted surgery are feasible and promising
      applications of robotic technology, whose main goals are surgical augmentation,
      information enhancement and improved surgical action. Neurosurgery probably
      presents the most major challenges, and can considerably benefit from the
      introduction of computers and robots to guide surgical procedures. This paper
      presents an innovative master-slave haptic robotic system for minimally invasive
      neurosurgery, which can help surgeons overcome human shortcomings and perform
      more accurate, repeatable, and reliable stereotactic neurosurgery. The system,
      named LANS, consists of a slave mechatronic actuator and a haptic master. The
      slave is designed to move linearly a laser pointer, a biopsy needle or a low
      energy X-ray emitter along a pre-planned axis. The tool insertion into the brain
      is guided by the surgeon through the haptic master which also provides force
      feedback to the operator. Not only can the haptic master reproduce the contact
      force between the surgical tool and the treated tissue, but it can also produce
      virtual forces aimed at assisting surgeons during the operations. Experiments
      have been conducted to prove the soundness and accuracy of the overall system
      mechanical design and to assess the effectiveness of the control schemes
      synthesized for the master and the slave.

PMID- 17518381
TI  - Preoperative planning system for surgical robotics setup with kinematics and
      haptics.
AB  - Recently, some useful robotic surgical systems have been developed and applied in
      many surgical situations. Systems such as the da Vinci surgical system of
      Intuitive Surgical Inc., which facilitates minimally invasive surgery with
      increased dexterity, are commercially available. Preoperative simulation and
      planning of surgical robot setups should accompany advanced robotic surgery if
      their advantages are to be further pursued. Feedback from the planning system
      will play an essential role in computer-aided robotic surgery in addition to
      preoperative detailed geometric information from patient CT/MRI images. Surgical
      robot setup simulation systems for appropriate trocar site placement have been
      developed especially for abdominal surgery. The motion of the surgical robot can
      be simulated and rehearsed with kinematic constraints at the trocar site, and the
      inverse-kinematics of the robot. Results from simulation using clinical patient
      data verify the effectiveness of the proposed system.

PMID- 17518382
TI  - Multi-imager compatible actuation principles in surgical robotics.
AB  - Today's most successful surgical robots are perhaps surgeon-driven systems, such
      as the daVinci (Intuitive Surgical Inc., USA, www.intuitivesurgical.com). These
      have already enabled surgery that was unattainable with classic instrumentation;
      however, at their present level of development, they have limited utility. The
      drawback of these systems is that they are independent self-contained units, and
      as such, they do not directly take advantage of patient data. The potential of
      these new surgical tools lies much further ahead. Integration with medical
      imaging and information are needed for these devices to achieve their true
      potential. Surgical robots and especially their subclass of image-guided systems
      require special design, construction and control compared to industrial types,
      due to the special requirements of the medical and imaging environments. Imager
      compatibility raises significant engineering challenges for the development of
      robotic manipulators with respect to imager access, safety, ergonomics, and above
      all the non-interference with the functionality of the imager. These apply to all
      known medical imaging types, but are especially challenging for achieving
      compatibility with the class of MRI systems. Even though a large majority of
      robotic components may be redesigned to be constructed of MRI compatible
      materials, for other components such as the motors used in actuation, prescribing
      MRI compatible materials alone is not sufficient. The electromagnetic motors most
      commonly used in robotic actuation, for example, are incompatible by principle.
      As such, alternate actuation principles using "intervention friendly" energy
      should be adopted and/or devised for these special surgical and radiological
      interventions. This paper defines the new concept of Multi-Imager Compatibility
      of surgical manipulators and describes its requirements. Subsequently, the paper
      gives several recommendations and proposes new actuation principles for this
      concept. Several implementations have been constructed and tested, and the
      results are presented here. This is the first paper addressing these issues.

PMID- 17518383
TI  - MBARS: mini bone-attached robotic system for joint arthroplasty.
AB  - A report on a new active, miniature bone-attached, robotic system including its
      design, high level and low level control, is given together with a description of
      the system implementation and first experimental use. The system is capable of
      preparing the bone cavity for an implant during joint arthroplasty procedures.
      Without loss of generality, the report describes the implementation of the system
      for a Patellofemoral Joint Replacement procedure. The system is image-free and
      all planning is performed intra-operatively in the robot coordinate system,
      eliminating the need for external tracking systems in the operating room.
      Experiments were conducted using the first robot prototype and the results
      supported the feasibility of the concept. The methodology which is presented can
      be modified to other orthopaedic procedures and could improve the results in
      terms of accuracy and operational time. Moreover, it enables minimally invasive
      procedures and use of the next generation of more anatomically shaped implants.

PMID- 17518384
TI  - Robotic microsurgical vasovasostomy and vasoepididymostomy in rats.
AB  - Robotic and robotic assisted procedures are rapidly increasing in popularity
      amongst practicing surgeons and urologists. Robotic techniques are now commonly
      used to perform radical prostatectomies for prostate cancer and pyeloplasties for
      uretero-pelvic junction obstruction. Other robotic procedures include robotic
      assisted coronary artery bypass and partial nephrectomies. We initially studied
      the da Vinci surgical robot in order to determine the feasibility of adapting the
      robot to microsurgical vasovasostomy and vasoepididymostomy. In this paper, we
      describe our experience in developing a set of practice exercises using the da
      Vinci robot to prepare for these microsurgical procedures. We also review the
      design and results of our studies of robotic microsurgical vasovasostomy and
      vasoepididymostomy in rats.Finally, we discuss the potential future roles of
      robotic microsurgery in urology and surgery.

PMID- 17518386
TI  - Registration of different phases of contrast-enhanced CT/MRI data for computer
      assisted liver surgery planning: evaluation of state-of-the-art methods.
AB  - The exact localization of intrahepatic vessels in relation to a tumour is an
      important issue in oncological liver surgery. For computer-assisted preoperative
      planning of surgical procedures high quality vessel models are required. In this
      work we show how to generate such models on the basis of registered CT or MRI
      data at different phases of contrast agent propagation. We combine well
      established intensity-based rigid and non-rigid registration approaches using
      Mutual Information as distance measure with different masking strategies as well
      as intensity inhomogeneity correction for MRI data. Non-rigid deformations are
      modelled by multilevel cubic B-splines. Quantitative evaluations of 5 MRI and 5
      CT image pairs show that the liver moves rigidly 7.2 (+/- 4.2) mm on average,
      while the remaining non-rigid deformations range from 1.4-3 mm. As a result we
      find that masked rigid registration is necessary and in many cases also
      sufficient on clinical data. After non-rigid registration the matching shows no
      deviations in most cases.

PMID- 17518387
TI  - MEMSurgery: an integrated test-bed for vascular surgery.
AB  - Many surgical procedures require skillful manipulations of blood vessels,
      especially in conventional invasive or minimally invasive surgical procedures.
      Current surgical methods do not allow the surgeon to receive any real time
      feedback of the tissue properties when operating on the vessel. As a result, the
      unintentional application of excessive force may damage the blood vessel. To
      minimize such trauma, and to study the interaction of surgical instruments with
      the vessel structure, we have developed an integrated surgical testbed called
      MEMSurgery (Microelectromechanical Sensory augmented Surgery). The test-bed
      integrates four elements: a) force sensors mounted on surgical appliances, b) a
      feedback control mechanism utilizing the intrinsic mechanical properties of the
      blood vessel, c) feedback of the force applied on the tissue back to the surgeon
      through a haptic feedback device, and d) visual feedback by a graphical computer
      model of the vessel. Finally, we evaluate the performance of MEMSurgery by
      testing the hypothesis that the combination of haptic feedback, feedback control
      based on vascular mechanical properties, and real-time visual representation of
      the vessel will help the surgeon decrease the probability of applying excess
      force while occluding the blood vessel. To this end, we designed a rodent
      experimental model to obtain the ideal minimum occlusion force (MOF). After a
      series of human performance studies, and subsequent comparison to direct
      application of force on the forceps (without feedback), the results show that the
      probability of applying reasonable MOF increases from 35.5% to 80%. After a brief
      training period, the probability increases to 90%.

PMID- 17518388
TI  - Navigated control in functional endoscopic sinus surgery.
AB  - This study designs and evaluates a mechatronic system to assist ENT surgery,
      taking as an example a navigation controlled shaver as used in paranasal sinus
      surgery. The on/off status of the shaver is regulated automatically, depending on
      the current position of the shaver tip. The working space for the navigation
      controlled shaver is planned preoperatively as a three-dimensional model and is
      based on the individual patient's CT data. Within this area the shaver reacts to
      signals from the surgeon. If the tip of the shaver moves outside the predefined
      working space, the shaver's automatic drive control is interrupted by an
      electrical pulse. The planning software was evaluated using CT data sets from 32
      patients. The accuracy of the registration was analysed on an anatomical model
      with the aid of 451 measurements on titanium screws attached endonasally, whilst
      the implementation of the working space was evaluated on 5 technical models. The
      average time taken for segmenting the working space was found to be 4.23 minutes.
      The average accuracy of the shaver registration was 1.08 mm. The selected cavity
      was to be resected without any restrictions. The preoperatively determined
      working space was implemented with a mean deviation of 3.1 mm over all levels.
      The study proves the feasibility of a mechatronic assistance system taking as an
      example the navigation controlled shaver used in paranasal sinus surgery. In
      contrast to isolated CAS solutions, this conceptual approach provides for the
      redundancy of the surgeon and eases their cognitive burden. We can foresee
      numerous applications in ENT surgery of the future following the principle
      presented here, in the control systems of power tools such as cutters, high
      frequency scalpels and lasers.

PMID- 17518389
TI  - Increased safety in robotic paranasal sinus and skull base surgery with redundant
      navigation and automated registration.
AB  - We present an advanced version of our robotic setup for paranasal sinus surgery
      that was developed at the Department of Otorhinolaryngology, Head and Neck
      Surgery in Erlangen, Germany. The system was interconnected with a redundant
      navigation system for increasing intraoperative safety while performing
      telemanipulatory as well as fully automated maneuvers.In contrast to the previous
      "all in one" version, we built a modular three component setup. The basic feature
      of the computer navigation system is the "CAPPA ENT" station. The system
      references by automatically detecting a referencing frame mounted on a non
      invasive upper jaw mouthpiece. Software components of both systems, navigation
      and robotics were combined on one user interface. Accuracy as well as clinical
      applicability studies were carried out. For better surveillance and increased
      safety, we decided to evaluate the robots reproducibility errors and overall
      stereotactic accuracy by means of redundant navigational control on a phantom
      model for paranasal sinus and skull base surgery. Multiple measurements from 14
      CT-markers were taken representing different surgical approaches.A modular setup
      was designed and was deemed feasible in its size and weight dimensions as well as
      its maneuvrability for application in a routine operating room environment. The
      navigational feedback is integrated in real time in the robots user interface. In
      case of blocked visibility to the Dynamic Referencing Frame the robot powers down
      and activates the force torque sensor, thus softening all articulating joints. We
      found only adequate accuracies in pinpointing a specific CT-marker both in
      telemanipulatory and fully automated maneuvers. No significant offsets were
      observed evaluating accuracies for different surgical approaches.By using
      redundant navigation feedback, we were able to add another safety feature, the
      "loss of control" function, which shuts down any robotic action. However, no
      increase of the absolute accuracy was observed by adding this feature. We
      conclude that redundant navigational control does not make the robot more
      accurate, but it adds a potent safety feature to the system.

PMID- 17518390
TI  - New augmented reality and robotic based methods for head-surgery.
AB  - Within the framework of the collaborative research centre "Information Technology
      in Medicine--Computer and Sensor-Aided Surgery" (SFB414) new methods for
      intraoperative computer assistance of surgical procedures are being developed.
      The developed tools will be controlled by an intraoperative host which provides
      interfaces to the electronic health record (EHR) and intraoperative computer
      assisted instruments.The interaction is based on standardised communication
      protocols. Plug & work functions will allow easy integration and configuration of
      new components. Intraoperative systems currently under development are
      intraoperative augmented reality (AR) using a projector and via a microscope, a
      planning system for definition of complex trajectories and a surgical robot
      system. The developed systems are under clinical evaluation and showing promising
      results in their application.

PMID- 17518391
TI  - Computer-assisted training system for knee arthroscopy.
AB  - This paper presents an educational method for minimally invasive surgery,
      conceived in collaboration with educationalists and arthroscopists, and an
      integrated system to train a priori knowledge and to exercise manual dexterity.
      The approach is generally suitable for minimally invasive surgery interventions
      but has been developed specifically for knee arthroscopy. Based on a
      classification of the knowledge, the system provides multimedia modules to train
      anatomical and procedural knowledge and a surgical simulator for training
      perceptual motor skills. We have tested the system in making three surgeons
      perform a series of tests. The results show that performance increases with the
      degree of experience. We also delivered a usability questionnaire and evaluated
      the appreciation by the surgeons. The test results and the appreciation showed by
      the surgeons encourage the prosecution of the research.

PMID- 17518392
TI  - Intraoperative, fluoroscopy-based planning for complex osteotomies of the
      proximal femur.
AB  - Intertrochanteric osteotomy of the proximal femur is a surgical technique that
      aims at changing the orientation of the proximal part of the femur in the hip
      joint by removing a bone wedge between the trochanters. Due to its six degrees of
      freedom, it presents a complex planning problem for the surgeon. In this paper,
      we propose an intraoperative planning system for proximal femur osteotomies.
      Based on two fluoroscopic images taken during the procedure, a primitive femur
      model is reconstructed, which then allows the user to interactively determine the
      osteotomy parameters and perform the intervention with the help of a navigation
      system. Besides the fluoroscopic images, no other imaging is needed. Compared to
      the traditional approach, this system allows the intervention to be performed
      with higher precision and less radiation exposure for both patient and surgeon,
      requiring only little time overhead. An in vitro study has demonstrated the high
      accuracy and ease of use of this system.

PMID- 17518393
TI  - Towards robotic heart surgery: introduction of autonomous procedures into an
      experimental surgical telemanipulator system.
AB  - The introduction of telemanipulator systems into cardiac surgery enabled the
      heart surgeon to perform minimally invasive procedures with high precision and
      stereoscopic view. For further improvement and especially for inclusion of
      autonomous action sequences, implementation of force-feedback is necessary. The
      aim of our study was to provide a robotic scenario giving the surgeon an
      impression very similar to open procedures (high immersion) and to enable
      autonomous surgical knot tying with delicate suture material. In this
      experimental set-up the feasibility of autonomous surgical knot tying is
      demonstrated for the first time using stereoscopic view and force feedback.

PMID- 17518394
TI  - Detection of tumour infiltration in axonal fibre bundles using diffusion tensor
      imaging.
AB  - We present a method for the detection and quantification of white matter
      infiltration from human brain tumours based on Diffusion Tensor Imaging (DTI).
      Since white matter destruction alters the local diffusion properties, DTI has the
      potential to sensitively detect tumour infiltration and to quantify the degree
      thereof. Here, we consider three tumour patients with gliomas, two with and one
      without contralateral tumour progress. We use DTI to identify specific fibre
      systems, where infiltration has to be assessed. On this basis, the problem of
      arbitrary region of interest definition is solved such that tumour infiltration
      can be reliably quantified in particular fibre bundles. It is demonstrated at the
      Corpus Callosum (CC) and the Pyramidal Tract (PT) that fibre bundle infiltration
      can be well detected by specific visualisation techniques of diffusion tensor
      data. Infiltration of the CC is quantified by using a reliable method for the
      determination of diffusion properties inside particular fibre bundles. For an age
      normalised quantification of white matter infiltration we introduce the Integrity
      Index, which measures the diffusion anisotropy inside an infiltrated fibre bundle
      normalised by the diffusion anisotropy in a specific region of healthy fibre
      tissue. It turns out that the quantification of CC infiltration correlates with
      contralateral tumour progression and has the potential to serve as a surrogate
      marker for this process, which is crucial for surgical therapy decisions and
      intervention planning.

PMID- 17518395
TI  - Determination of the elasticity parameters of brain tissue with combined
      simulation and registration.
AB  - Reliable elasticity parameters describing the behavior of a given material are an
      important issue in the context of physically-based simulation. In this paper we
      introduce a method for the determination of the mechanical properties of brain
      tissue. Elasticity parameters Young's modulus E and Poisson's ratio nu are
      estimated in an iterative framework coupling a finite element simulation with
      image registration. Within this framework, the outcome of the simulation is
      parameterized with both elasticity moduli that are automatically varied until
      optimal image correspondence between the simulated and the intraoperative data is
      achieved. We calculated optimal mechanical properties of brain tissue in six
      cases. The statistical analysis of the obtained values showed a good correlation
      of the results, thus proving the value of the method. An approach combining
      simulation and registration for the determination of the mechanical brain tissue
      properties is presented. This contributes to performing reliable physically-based
      simulation of soft tissue movement.

PMID- 17518396
TI  - Development of actuated and sensor integrated forceps for minimally invasive
      robotic surger.
AB  - In minimally invasive surgery (MIS) the patient's skin forms a spatial barrier
      between the operation area and the surgeon. This prevents direct access to the
      operation site which causes a lack of dexterity and limits the sensation of
      tissue manipulation forces, therefore complicating MIS procedures significantly.
      A telepresence approach can overcome these limitations: Additional degrees of
      freedom (DoF) inside the patient provide full manipulability and force torque
      sensors at the distal end of the instrument allow precise measurement of
      interaction forces. Using a suitable man-machine interface and free cartesian
      motion kinaesthetic feedback can be achieved, thus providing a virtual open
      surgery environment to the surgeon. This article focuses on the development and
      first results of actuated and sensor integrated instruments as part of the DLR
      minimally invasive robotic surgery (MIRS) setup. The instruments as a front-end
      part of the MIRS setup form one base of a telepresence working environment and
      are crucial for semi-autonomous functions, e.g. motion compensation.

PMID- 17518397
TI  - A robotic C-arm fluoroscope.
AB  - Fluoroscopic C-arms are common devices for acquiring images during surgery.
      Manual positioning is time consuming and requires considerable experience.
      Trained users must often take several images to find the best viewing direction.
      If a second image must be taken from the same position, e.g. for postoperative
      control, the C-arm must be moved to the exact same position. Without guidance,
      this is often difficult to accomplish. We developed the idea to completely
      "robotize" a standard C-arm, i.e. to equip all joints with motors and encoders. A
      software environment provides for intelligent control. To archive this goal a
      complete kinematic analysis of the fluoroscope was necessary. On the basis of
      this analysis a number of clinical applications have been developed: (1)
      simplified positioning via cartesian control; (2) automatic acquisition of
      panoramic images; (3) 3D CT with arbitrary viewing angles; (4) 4D intraoperative
      CT with/without respiration triggering; (5) automated anatomy-oriented
      positioning. The goal of this research is thus three-fold: minimise radiation
      exposure of the OR staff, reduce positioning time and offer enhanced imaging
      capability.

PMID- 17518399
TI  - "MIS meets CAOS"--less and minimally invasive joint reconstruction.

PMID- 17518400
TI  - Robotic systems in total hip arthroplasty--is the time ripe for a new approach?
AB  - The technical aspects of manual total hip arthroplasty are briefly described. The
      development, technique and technical problems of previous robotic systems in
      total hip arthroplasty are described with special details of the Robodoc--System.
      Recent advances regarding the minimally invasive technique of total-hip
      implantation and navigation are described. The current development of a robotic
      assisted system for total hip arthroplasty is presented. This project aims to
      combine the advantages of minimally invasive techniques and navigational systems
      with the accuracy that robotic assisted bone milling can provide. The project
      name is RomEo (Robotic minimally invasive Endoprosthetics), the main project
      partners are the Helmut-Schmidt-University/Hamburg and the Department of Trauma
      and Orthopaedics of the BG Trauma Hospital Hamburg.

PMID- 17518401
TI  - Robotic clinical trials of uni-condylar arthroplasty.
AB  - A randomised clinical trial has been completed for uni-condylar arthroplasty. The
      trial, under the auspices of the UK MHRA, comprised 15 knees of patients
      undergoing conventional surgery, and 13 knees of patients who had robotic surgery
      using the Acrobot hands-on robotic system. The results of the trial were checked
      by comparing post-op CT scans with pre-op CT-based plans, and show a significant
      improvement in accuracy using the robot. The technical concept of the Acrobot
      approach is also described. Details of the complete system are outlined,
      including the pre-operative planner. The plan incorporates 3D CT models of the
      leg, together with CAD models of prostheses that can be used to plan the leg
      alignment, position the prostheses, plan the shape of the cuts required and
      generate the regions within which cuts must be constrained. The robotic system is
      also described, together with the methods for locating, clamping, cutting and
      monitoring the patient. An outline is given of the means by which the
      preoperative model is registered or aligned to the intra-operative position of
      the patient and of the robot, without the need for fiducial markers. Results of
      the randomised clinical trial are also discussed.

PMID- 17518402
TI  - Computer assisted pedicle screw fixation: clinical experience with a newly
      developed software.
AB  - We have used software, recently developed at Cochin University of Science and
      Technology, to perform computer assisted pedicle screw placement in forty
      pedicles of ten patients with fractured thoracolumbar vertebrae from January 2002
      to February 2004. A pre-operative CT scan section at the pedicle level is taken
      one vertebra above and one below the involved vertebra. The dicom image is
      converted into a bitmap image and reference lines are drawn through the
      transverse processes and the spinous processes. The screw trajectory is drawn in
      the image at the most suitable path of the pedicle. Intraoperatively reference
      pins are placed exactly at the same areas in the transverse processes and the
      spinous processes. The intraoperative image is live captured using a camera and
      is matched with the preoperative image and the awl is advanced into the pedicle
      corresponding to the screw trajectory in the CT image. Out of forty pedicles
      instrumented in ten patients using computer assistance, the pedicle wall
      violation as demonstrated with 1 mm thin CT scans was less than AMIOT Grade 2.
      Ideal placement was noted in 80% and clinically insignificant perforation (Grade
      2&3) in the rest. Computer assisted pedicle screw fixation appears to be a good
      technique for the accurate placement of pedicle screws in fractured vertebrae.

PMID- 17518403
TI  - Computer assisted orthopaedic surgical system for insertion of distal locking
      screws in intra-medullary nails: a valid and reliable navigation system.
AB  - The insertion of distal locking screws is a difficult task in intra-medullary
      (IM) nailing operations of long bones and contributes a significant proportion to
      the overall operating time. The current technique to insert these screws uses
      numerous fluoroscopic images and depends on the skills and expertise of the
      surgeon. The Computer Assisted Orthopaedic Surgical System (CAOSS) was developed
      to assist orthopaedic surgeons in these operations. The laboratory based test
      results for insertion of distal locking screws in IM nailing procedures are
      presented and discussed in terms of accuracy and as part of the validation
      process to introduce new CAOS procedures into clinical use. This study shows that
      CAOSS in IM nailing is robust and reliable. Positional accuracy was shown to be
      within 0.3 mm and angular accuracy within 0.2 degrees with femoral IM nail. CAOSS
      was also shown to be very reliable and accurate at different angles of distal
      screws in fluoroscopic image space.

PMID- 17518404
TI  - Mini-invasive computer assisted bi-unicompartimental knee replacement.
AB  - In the treatment of knee osteoarthritis there are no reports using bi
      unicompartimental implants and many orthopaedic surgeons are sceptical about this
      demanding surgical procedure despite its theoretical advantages in terms of less
      invasive surgery. The bi-unicompartmental approach also offers the potential
      advantage of maximal preservation of normal anatomy, with benefits for functional
      aspects such as gait, muscle activity, and proprioception.Computer-aided knee
      replacement surgery has been gaining popularity and an improvement in limb
      alignment and kinematics has been demonstrated in several studies. During the
      procedure the surgeon can check both implant position and ligament balance during
      the full range of joint movements, which helps to reduce the complications
      traditionally associated with failure in the past. The authors present a computer
      aided technique for performing bi-unicompartimental knee replacement which
      permits a less invasive alternative for knee replacement surgery.

PMID- 17518405
TI  - Automated hydraulic tensor for Total Knee Arthroplasty.
AB  - To obtain a long lifespan of knee prosthesis, it is necessary to restore the
      alignment of the lower limb. In some cases of severe arthrosis, the ligament
      envelope of the joint may be deformed, inducing an asymmetric laxity once the
      lower limb is realigned. Because there is not yet unanimity regarding how to
      optimally measure or implement soft tissue balance, we provide a means to acquire
      a variety of measurements. In traditional surgery, the surgeon sometimes uses a
      "tensor", which acts like a forceps. This system was redesigned, instrumented,
      actuated, and integrated into a navigation system for orthopaedic surgery.
      Improving the perception of the surgeon, it helps him to address the ligament
      balancing problem. Our first prototype has been tested on sawbones before being
      validated in an experiment on two cadavers. In our first attempt, the surgeon was
      able to assess soft tissue balance but judged the device not powerful enough,
      which led us to develop a new more powerful hydraulic system. In this paper, we
      present our approach and the first results of the new hydraulic tensor which is
      currently in an integration process.

PMID- 17518406
TI  - Computer-assisted access to the kidney.
AB  - OBJECTIVES: The aim of this paper is to introduce the principles of computer
      assisted access to the kidney. The system provides the surgeon with a pre
      operative 3D planning on computed tomography (CT) images. After a rigid
      registration with space-localized ultrasound (US) data, preoperative planning can
      be transferred to the intra-operative conditions and an intuitive man-machine
      interface allows the user to perform a puncture. MATERIAL AND METHODS: Both CT
      and US images of informed normal volunteer were obtained to perform calculation
      on the accuracy of registration and punctures were carried out on a kidney
      phantom to measure the precision of the whole of the system. RESULTS: We carried
      out millimetric registrations on real data and guidance experiments on a kidney
      phantom showed encouraging results of 4.7 mm between planned and reached targets.
      We noticed that the most significant error was related to the needle deflection
      during the puncture. CONCLUSION: Preliminary results are encouraging. Further
      work will be undertaken to improve efficiency and accuracy, and to take breathing
      into account.

PMID- 17518407
TI  - Praxiteles: a miniature bone-mounted robot for minimal access total knee
      arthroplasty.
AB  - We have been working to develop a compact, accurate, safe, and easy-to-use
      surgical robot for minimally invasive total knee arthroplasty (TKA). The goal of
      our bone-mounted robot, named Praxiteles, is to precisely position a surgical
      bone-cutting guide in the appropriate planes surrounding the knee, so that the
      surgeon can perform the planar cuts manually using the guide. The robot
      architecture is comprised of 2 motorized degrees of freedom (DoF) whose axes of
      rotation are arranged in parallel, and are precisely aligned to the implant
      cutting planes with a 2 DoF adjustment mechanism. Two prototypes have been
      developed and tested on saw bones and cadavers--an initial one for open TKA
      surgery and a new version for MIS TKA, which mounts on the side of the knee. A
      novel bone-milling technique is also presented that uses passive guide and a side
      milling tool.

PMID- 17518408
TI  - Tele-surgery simulation with a patient organ model for robotic surgery training.
AB  - Robotic systems are increasingly being incorporated into general laparoscopic and
      thoracoscopic surgery to perform procedures such as cholecystectomy and
      prostatectomy. Robotic assisted surgery allows the surgeon to conduct minimally
      invasive surgery with increased accuracy and with potential benefits for
      patients. However, current robotic systems have their limitations. These include
      the narrow operative field of view, which can make instrument manipulation
      difficult. Current robotic applications are also tailored to specific surgical
      procedures. For these reasons, there is an increasing demand on surgeons to
      master the skills of instrument manipulation and their surgical application
      within a controlled environment. This study describes the development of a
      surgical simulator for training and mastering procedures performed with the da
      Vinci surgical system. The development of a tele-surgery simulator and the
      construction of a training center are also described, which will enable surgeons
      to simulate surgery from or in remote places, to collaborate over long distances,
      and for off-site expert assistance.

PMID- 17518409
TI  - Recording forces exerted on the bowel wall during colonoscopy: in vitro
      evaluation.
AB  - A novel system for distributed force measurement between the bowel wall and the
      shaft of a colonoscope is presented. The system, based on the piezoresistive
      method, involves the integration of soft miniature transducers to a colonoscope
      to enable a wide range of forces to be sensed. The attached sensing sheath does
      not restrict the propulsion of the colonoscope nor notably alter its flexibility.
      The addition of the sensor sheath increases the colonoscope diameter by 15-20%
      depending on the type of the colonoscope (adult or paediatric). The transducer's
      accuracy is +/-20 grammes if it is not subjected to extensive static forces.
      Under large static force conditions the errors may increase to +/-50 grammes. The
      tactile force measuring sensors have provided preliminary results from
      experiments on a model of the large bowel. The force measurements confirm the
      predictions on the location and magnitude of the forces and that most of the
      forces are exerted whilst the instrument is looping.

PMID- 17518410
TI  - Navigation of bone alignment osteotomies of the tibia.
AB  - This article describes a new bone segment navigation device for application in
      orthopaedic surgery. It allows for exact and CT-free alignment of bone segments
      according to a preset plan. The system guides the user through the initialisation
      process with only minor interaction. Once the bone segments are registered, an
      intuitive graphical model visualizes current spatial position relative to a
      desired (initial or planned) position. Advantages of the system are the usability
      without CT data and a very simple user interface. We describe the system, its
      components and the method of operation. Furthermore, an initial experiment to
      measure the overall repositioning accuracy during an experimental intervention is
      described, which was performed to access biomechanical information for the
      clinical analysis of osseo-integration processes is presented.

PMID- 17518411
TI  - The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a
      prospective study.
AB  - PURPOSE: The primary purpose of this study was to evaluate the cognitive effects
      of adjuvant chemotherapy in post-menopausal breast cancer patients. PATIENTS AND
      METHODS: Breast cancer patients scheduled to receive adjuvant chemotherapy (n =
      61) completed comprehensive cognitive testing before and after treatment. A
      control group of women receiving adjuvant hormonal therapy (n = 51) was tested at
      comparable intervals. RESULTS: Mean scores for both patient groups were within
      the normal range relative to published norms on all cognitive tests at both time
      points, and generally inclined or stayed the same from baseline to retest in both
      groups. However, in an analysis of individual change scores, the chemotherapy
      patients were 3.3 times more likely than the hormonal patients to show reliable
      cognitive decline (31 and 12%, respectively). Chemotherapy subjects showing
      decline were less educated and had higher baseline depression scores than their
      counterparts who did not decline. Working memory was the cognitive domain most
      vulnerable to the effects of chemotherapy. CONCLUSION: These data support
      previous findings of a subtle negative influence of chemotherapy on cognitive
      function in a subgroup of breast cancer patients. The results are discussed in
      terms of the importance of study design.

PMID- 17518412
TI  - Assessing pre-death grief in cancer caregivers using the Marwit-Meuser Caregiver
      Grief Inventory (MM-CGI).
AB  - The Marwit-Meuser Caregiver Grief Inventory (MM-CGI) was developed and initially
      validated with caregivers of persons with Alzheimer's disease, and subsequently
      evaluated with caregivers of persons with brain injury. The present study
      examined MM-CGI psychometric and validity properties in 75 caregivers of persons
      with cancer. As with previous studies, high internal consistency reliability of
      MM-CGI Total Grief and subscale scores (Personal Sacrifice and Burden, Heartfelt
      Sadness and Longing, and Worry and Felt Isolation) was demonstrated. Construct
      validity of the subscale scores was supported by differential associations with
      other caregiver measures of depression, strain, well-being, and family support.
      Based on these preliminary results, the MM-CGI appears useful for assessing pre
      death grief in caregivers of persons with cancer.

PMID- 17518413
TI  - Production, purification, and characterization of a novel galactose oxidase from
      Fusarium acuminatum.
AB  - Extra-cellular production of a novel galactose oxidase from Fusarium acuminatum
      using submerged fermentation was studied. Glucose (1.0% w/v) was used as the sole
      carbon source. Maximum galactose oxidase production (approximately 4.0 U/ml) was
      obtained when fermentation was carried out at 25 degrees C, with orbital shaking
      (100 rpm) and an initial medium of pH 7.0, for 96 h, using a 2% (v/v) inoculum
      made from a homogenized four-day-old liquid culture, in the presence of copper,
      manganese, and magnesium. The enzyme was purified by one-step affinity
      chromatography, with a recovery of 42% of the initial activity. The purified
      enzyme ran as a single band of 66 kDa in SDS-PAGE. Optimal pH and temperature for
      the enzyme activity were 8.0 and 30 degrees C, respectively. The enzyme was
      thermoinactivated at temperatures above 60 degrees C. The purified enzyme was
      active toward various substrates, including galactose, dihydroxyacetone, guar
      gum, lactose, melibiose, methyl-galactopyranoside, and raffinose. SDS was an
      inhibitor but EDTA, Tween 80, NH(4)(+), Na(+), Mg(2+), K(+), and glycerol were
      not. The Michaelis-Menten constant (K(m)) for galactose was estimated to be 16.2
      mM, while maximal velocity (V(max)) was 0.27 micromol of H(2)O(2) . ml(-1) . min(
      1).

PMID- 17518414
TI  - Moderately halophilic, alkalitolerant Halomonas campisalis MCM B-365 from Lonar
      Lake, India.
AB  - Seven bacterial isolates obtained from sediment and water samples, collected from
      the alkaline Lonar Lake were identified on the basis of their morphological,
      physiological and biochemical characteristics and were confirmed by 16S rDNA
      sequencing to be Halomonas campisalis. They were capable of using a variety of
      electron donors and were found to grow in the presence of sodium chloride (NaCl)
      up to 4 M, at pH from 7 to 11, 9 being the optimum. The isolates could grow over
      a wide range of temperatures (from 4 to 45 degrees C) and showed temperature
      dependent salt tolerance. They exhibited requirement of sodium for growth and
      could grow in any medium where NaCl is replaced by NaNO(3) and Na(2)S(2)O(3) but
      not in the presence of salts like LiCl, MgCl(2) . 6H(2)O, KCl and NH(4)Cl. One of
      the seven isolates, ARI 351, was able to produce lipase at pH-9.0, while two
      isolates, ARI 351 and ARI 360, could accumulate polyhydroxyalkanoic acid (PHA)
      granules when grown in a medium containing maltose. Thus the H. campisalis
      isolated from Lonar Lake was different from the previously reported one, with
      respect to its biotechnological potential for production of Lipase and PHA.

PMID- 17518415
TI  - Cell cycle dependent phosphatase activity in Bacillus subtilis.
AB  - In Bacillus subtilis there is evidence that the replication origin of the DNA
      molecule is attached to the cytoplasmic membrane, and that this attachment is
      essential for the initiation of replication. We have previously shown that
      attachment of DNA to the membrane is cyclic and that DNA becomes attached to the
      cytoplasmic membrane at the beginning of replication and is subsequently
      released. We have also shown that membrane protein phosphorylation is associated
      with the initiation of DNA replication in B. subtilis. We now report that
      cantharidin, an inhibitor of eukaryotic serine/threonine protein phosphatases
      type 1 and 2A, stimulated membrane binding of DNA and caused premature initiation
      of DNA replication in B. subtilis cells. The membrane of B. subtilis cells had
      cell cycle dependent phosphatase activity against a standard substrate in vitro.
      Cloning of the B. subtilis protein PrpE and production of antibodies allowed us
      to identify the protein in the cytoplasmic membrane. Its presence was cell cycle
      dependent, and appeared to contribute to the observed phosphatase activity.

PMID- 17518416
TI  - Antimicrobial mechanisms of ortho-phthalaldehyde action.
AB  - Biocides generally have multiple biochemical targets. Such a feature easily
      entangles the analysis of the mechanisms of antimicrobial action. In this study,
      the action of the dialdehyde biocide ortho-phtalaldehyde (OPA), on bacteria, was
      investigated using the Gram-negative Pseudomonas fluorescens. The targets of the
      biocide action were studied using different bacterial physiological indices. The
      respiratory activity, membrane permeabilization, physico-chemical
      characterization of the bacterial surfaces, outer membrane proteins (OMP)
      expression, concomitant influence of pH, contact time and presence of bovine
      serum albumin (BSA) on respiratory activity, morphological changes and OPA-DNA
      interactions were assessed for different OPA concentrations. With the process
      conditions used, the minimum inhibitory concentration was 1500 mg/l, the
      concentration to promote total loss of bacterial culturability was 65 mg/l and
      the concentration needed to inactivate respiratory activity was 80 mg/l. These
      data are evidence that culturability and respiratory activity were markedly
      affected by the biocide. OPA lead, moreover, to a significant change in cell
      surface hydrophobicity and induced propidium iodide uptake. Such results suggest
      cytoplasmic membrane damage, although no release of ATP was detected. At pH 5,
      the bactericidal action of OPA was stronger, though not influenced by BSA
      presence. Nevertheless, at pH 9, BSA noticeably (p < 0.05) impaired biocide
      action. A time-dependent effect in OPA action was evident when contemplating
      respiratory activity variation, mainly for the lower exposure times. Scanning
      electron microscopy allowed to detect bacterial morphological changes, translated
      on cellular elongation, for OPA concentrations higher than 100 mg/l.
      Interferences at DNA level were, however, restricted to extreme biocide
      concentrations. The overall bactericidal events occurred without detectable OMP
      expression changes. In conclusion, the results indicated a sequence of events
      responsible for the antimicrobial action of OPA: it binds to membrane receptors
      due to cross-linkage; impairs the membrane functions allowing the biocide to
      enter through the permeabilized membrane; it interacts with intracellular
      reactive molecules, such as RNA, compromising the growth cycle of the cells and,
      at last, with DNA.

PMID- 17518417
TI  - Discaria trinervis - Frankia symbiosis promotion by saprophytic actinomycetes.
AB  - The influence of saprophytic actinomycetes strains on the Discaria trinervis -
      Frankia actinorhizal symbiosis was investigated. Three strains out of 122
      isolated from the rhizosphere and rhizoplane of D. trinervis with multiple
      enzymatic activities, were selected for plant growth experiments: Streptomyces
      (BCRU-MM40), Actinoplanes (BCRU-ME3) and Micromonospora (BCRU-MM18). Inoculated
      seedlings of Discaria trinervis were grown in glass tubes with vermiculite-sand
      for 12 weeks. They were inoculated either with a single saprophytic strain or a
      combination of one or two of them together with the symbiotic N(2) fixing strain
      Frankia BCU110501. The saprophytic strains were applied in two experimental
      series, i.e. mycelium + supernatant simultaneously or mycelium and supernatant
      (growth medium free of cells) separately. Micromonospora strain MM18 showed a
      direct promotion effect on shoot growth, when plants were inoculated with
      mycelium and supernatant together. Streptomyces strain MM40 and Actinoplanes
      strain ME3 promoted the actinorhizal symbiosis with Frankia and consequently the
      development of plant shoots, when supernatant was involved as inoculum. It is
      supposed, that the strains MM18, MM40 and ME3 produce bioactive metabolites,
      which are released into the culture medium. The saprophytic strains studied could
      be considered as "promoting or helper rhizoactinomycetes" of the actinorhizal
      plant D. trinervis.

PMID- 17518418
TI  - Bacterial cell division protein FtsZ is stable against degradation by AAA family
      protease FtsH in Escherichia coli cells.
AB  - We have found that FtsH protease of Escherichia coli could degrade E. coli cell
      division protein FtsZ in an ATP- and Zn(2+)-dependent manner in vitro and that
      the degradation did not show specificity for the N-terminus or C-terminus of
      FtsZ, like in the case of degradation of its conventional substrate sigma(32)
      protein. In continuation of these observations, in the present study, we examined
      whether FtsH would affect the stability and turnover of FtsZ in vivo. We found
      that FtsZ levels were not elevated in E. coli AR754 (ftsH1 ts) cells at
      nonpermissive temperature as compared to the levels in an FtsH-active isogenic
      AR753 strain. Neither did FtsH degrade ectopically expressed FtsZ in AR754 strain
      nor did ectopic expression of FtsH reduced FtsZ levels in E. coli AR5090 ftsH
      null strain (ftsH::kan, sfhC21). Pulse chase experiments in AR754 and AR5090
      strains showed that there were no compensatory changes in FtsZ turnover, in case
      FtsZ degradation had occurred. Even under cell division arrested conditions,
      wherein FtsZ was not required, FtsH protease did not degrade unutilized FtsZ.
      These experiments demonstrate that either FtsH protease may not have a role in
      regulating the levels of FtsZ in vivo under the conditions tested or that some
      cellular component(s) might be stabilising FtsZ against FtsH protease.

PMID- 17518419
TI  - Molecular characterization of the non-coding promoter and leader regions and full
      length 16S ribosomal RNA (rRNA) gene of Taylorella asinigenitalis.
AB  - The 3,339 base pair (bp) sequences encoding a putative open reading frame (ORF),
      non-coding promoter and leader regions (approximately 320 bp), full-length 16S
      ribosomal RNA (rRNA) gene (approximate 1,540 bp) and part of the 16S-23S rDNA
      internal spacer region (ISR) were determined from genome DNA libraries of the
      Taylorella asinigenitalis (UK-1) isolate. The non-coding promoter and leader
      regions included antiterminators (boxB, boxA and boxC) immediately upstream of
      the 16S rRNA gene sequence. An approximately 680 bp region upstream of the non
      coding promoter region appears to contain a putative ORF with high sequence
      similarity to GTP cyclohydrolase I. In addition, a typical order of
      intercistronic tRNA genes with the 48 nucleotide spacer of 5'-16S rDNA-tRNA(Ile)
      tRNA(Ala)-23S rDNA-3' was demonstrated in a part of the 16S-23S rDNA ISR. The
      antiterminators of boxB and boxA were also identified in the ISR.A phylogenetic
      analysis based on the 16S rRNA gene sequence information clearly demonstrated
      that the five T. asinigenitalis isolates formed a cluster together with the three
      T. equigenitalis strains, more similar to Pelistega europaea than the other beta
      Proteobacteria from the 13 species of 11 genera.

PMID- 17518420
TI  - Isolation of a FAD-GPDH gene encoding a mitochondrial FAD-dependent glycerol-3
      phosphate dehydrogenase from Dunaliella salina.
AB  - The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase (FAD-GPDH),
      recently reported in plants, has been detailed in yeast and animal systems. It
      oxidizes glycerol-3-phosphate (G-3-P) to dihydroxyacetone phosphate (DHAP) on the
      outer surface of mitochondrial inner membrane. A cDNA encoding the Dunaliella
      salina mitochondrial glycerol-3-phosphate dehydrogenase (DsFAD-GPDH) has been
      cloned and sequenced. The full length cDNA is 2791 bp, with an open reading frame
      (ORF) encoding 650 predicted amino acids, which show strong homology to reported
      FAD-GPDHs and have an apparent mitochondrial targeting sequence in the N
      terminal. The sequence has been submitted to the GenBank database under Accession
      No. DQ916107. Results of Real-Time Quantitative PCR and enzymatic assays show
      that expression of DsFAD-GPDH is enhanced at first by salt treatment, and
      repressed by oxygen deficiency and cold stress.

PMID- 17518421
TI  - Effect of inoculation with Penicillium albidum, a phosphate-solubilizing fungus,
      on the growth of Trifolium pratense cropped in a volcanic soil.
AB  - Volcanic soils in the south of Chile have an elevated quantity of total P, which
      is scarcely available due to its high P fixation capacity. One strategy for
      increasing the availability of P for the vegetables that grow there would be to
      use phosphate-solubilizing microorganisms. In one assay conducted in a greenhouse
      on a volcanic soil, the effect of inoculation with Penicillium albidum, a
      phosphate-solubilizing fungus, was studied on the growth of red clover (Trifolium
      pratense L). Some chemical and biological properties of the soil were also
      evaluated. There were three treatments: a) active inoculum [In(+)], b) inactive
      inoculum (autoclaved) [In(-)] and c) without inoculum [In(0)], each one done in
      three replicates. The In(+) significantly (P < 0.050) increased the growth of the
      plants, contributing particularly to root development. The P mobilized to the
      shoot with In(+) was higher than twofold related to In(0) and In(-) treatments;
      however, the In(+) plants had similar concentration of shoot P. In the soil,
      available-P was not statistically different (P < 0.050) among the treatments but
      phosphatase activity in In(+) was higher (P < 0.050) in comparison to In(0). The
      results suggest that Penicillium albidum contributed to growth and nutrition of
      the red clover through the induction of root development and enhancing phosphate
      mobilization from the soil and into the plant. It is concluded that Penicillium
      albidum, under greenhouse conditions, in soils deficient in available P can
      increase the inoculation potential for volcanic soils in Chile. Anyway further
      studies are required, especially in organic farming where the use of soluble P
      fertilizer is avoided.

PMID- 17518422
TI  - Efficient transformation of Lactococcus lactis IL1403 and generation of knock-out
      mutants by homologous recombination.
AB  - Lactococcus lactis IL1403 is a Gram-positive bacterium of great biotechnological
      interest for food grade applications. Its use is however hampered by the
      difficulty to efficiently transform this strain. We here describe a detailed,
      optimized electrotransformation protocol which yields a transformation efficiency
      of 10(6) cfu/microg of DNA with the two E. coli Gram-positive shuttle vectors pC3
      and pVA838. The utility of the protocol was demonstrated by the generation of
      single- and double-knock-out mutants by homologous recombination.

PMID- 17518423
TI  - Abnormal first-trimester ductus venosus blood flow: a risk factor for adverse
      outcome in fetuses with normal nuchal translucency.
AB  - OBJECTIVES: First-trimester nuchal translucency thickness (NT) is a potent tool
      for assessment of fetal risks of aneuploidy and other adverse outcomes. When NT
      is increased, Doppler assessment of the ductus venosus (DV) enhances the
      prediction specificity for Down syndrome. This study assessed abnormal Doppler DV
      waveform as a predictor of adverse outcome when the NT is normal. METHODS: This
      was a case-control study of 2,505 consecutive patients undergoing NT screening in
      our certified first-trimester screening program. First-trimester Doppler
      assessment of DV was performed and atrial systolic velocity was rated as
      antegrade (normal) or absent/reversed (DV-RAV; abnormal). Each case with normal
      NT (< 95(th) percentile) and DV-RAV was matched with two controls with respect to
      maternal age within 1 year, NT within 0.2 mm, crown-rump length within 3 mm, and
      closest calculated aneuploidy risk. Outcomes for paired variables were compared
      using t-test and Chi-square test. RESULTS: Forty-seven (1.9%) patients had normal
      NT and DV-RAV. After exclusion of three cases with obvious first-trimester
      anomalies and two with incomplete outcome data, 42 remained for analysis. Adverse
      outcome included cardiovascular defects (n = 6), fetal growth restriction (n =
      3), renal anomaly (n = 2), aneuploidy (n = 3) and multiple defects (n = 3), in a
      total of 11/42 cases (26.2%). Cardiac abnormalities, renal abnormalities and
      perinatal death were all significantly more common in the study group (all P <
      0.05). CONCLUSIONS: Abnormal first-trimester DV Doppler findings appear to
      predict adverse outcome independently of a normal NT. These patients need
      detailed mid-trimester assessment of fetal anatomy with formal echocardiography,
      and subsequent follow-up.

PMID- 17518428
TI  - Chemistry in cancer research: a vital partnership.

PMID- 17518429
TI  - Making bacteria behave: new agonists and antagonists of quorum sensing.
AB  - Small-molecule agonists and antagonists of bacterial quorum sensing can enhance
      our understanding of this form of cell-cell communication. A recent effort has
      discovered effective modulators of the autoinducer-1 circuit for bacterial quorum
      sensing by the synthesis and evaluation of a small library of aryl-substituted
      acyl-homoserine lactone analogues. This series highlights the sensitivity to
      structure of the contrasting responses of agonism and antagonism of the natural
      signal and identifies an analogue that provokes the same response as the natural
      signal but at 10-fold lower concentration, a "superagonist".

PMID- 17518430
TI  - Revealing coupling patterns in isoprenoid alkylation biocatalysis.
AB  - Diversity of scaffold structure and function is a hallmark of the >50,000
      isoprenoid natural products such as taxol. Whereas most members of this class are
      assembled by iterative head-to-tail enzymatic joining reactions between delta2-
      and delta3-isopentenyl diphosphate (IPP) monomers, dimerization of two delta2-IPP
      molecules has now been shown to account for three additional modes of "irregular"
      coupling patterns at the level of C10 monoterpene scaffolds.

PMID- 17518431
TI  - Using chemical genetics and ATP analogues to dissect protein kinase function.
AB  - Protein kinases catalyze the transfer of the gamma-phosphate of ATP to a protein
      substrate and thereby profoundly alter the properties of the phosphorylated
      protein. The identification of the substrates of protein kinases has proven to be
      a very difficult task because of the multitude of structurally related protein
      kinases present in cells, their apparent redundancy of function, and the lack of
      absolute specificity of small-molecule inhibitors. Here, we review approaches
      that utilize chemical genetics to determine the functions and substrates of
      protein kinases, focusing on the design of ATP analogues and protein kinase
      binding site mutants.

PMID- 17518432
TI  - Structural basis for high-affinity peptide inhibition of human Pin1.
AB  - Human Pin1 is a key regulator of cell-cycle progression and plays growth
      promoting roles in human cancers. High-affinity inhibitors of Pin1 may provide a
      unique opportunity for disrupting oncogenic pathways. Here we report two high
      resolution X-ray crystal structures of human Pin1 bound to non-natural peptide
      inhibitors. The structures of the bound high-affinity peptides identify a type-I
      beta-turn conformation for Pin1 prolyl peptide isomerase domain-peptide binding
      and an extensive molecular interface for high-affinity recognition. Moreover,
      these structures suggest chemical elements that may further improve the affinity
      and pharmacological properties of future peptide-based Pin inhibitors. Finally,
      an intramolecular hydrogen bond observed in both peptide complexes mimics the
      cyclic conformation of FK506 and rapamycin. Both FK506 and rapamycin are
      clinically important inhibitors of other peptidyl-prolyl cis-trans isomerases.
      This comparative discovery suggests that a cyclic peptide polyketide bridge, like
      that found in FK506 and rapamycin or a similar linkage, may significantly improve
      the binding affinity of structure-based Pin1 inhibitors.

PMID- 17518433
TI  - Molecules in glass: probes, ordered assemblies, and functional materials.
AB  - Research on the properties and applications of molecules doped into sol-gel
      derived silica matrices has expanded rapidly. This Account begins with a brief
      review of the use of the dopant molecules as probes of the changes that occur as
      the system evolves from the initial sol to the final xerogel during the formation
      of monoliths, thin films, and mesostructured films. Methods of deliberately
      placing desired molecules in specific regions of the mesostructure are discussed,
      and an application, energy transfer, is presented. Finally, encapsulation of
      biological molecules is examined, and two important aspects, stabilization of the
      biomolecules and applications as biosensors, are described.

PMID- 17518434
TI  - Annulenylenes, annulynes, and annulenes.
AB  - A number of techniques have been found to generate annulynes. Some of the
      annulynes have been found to spontaneously dimerize to biannulenylenes and to
      form triannulenylenes. The reaction products, thermodynamics, and kinetic
      stabilities of the annulenylenes, annulynes, and their parent annulenes prove to
      be extremely dependent upon the number of pi electrons. In fact, the addition of
      an extra electron can trap some "fugitive" systems and render them sufficiently
      stable for spectroscopic study. Even the number of neutrons can perturb the
      conjugation and, presumably, the stability of annulenes that have internal
      protons.

PMID- 17518435
TI  - Substrate trafficking and dioxygen activation in bacterial multicomponent
      monooxygenases.
AB  - Non-heme carboxylate-bridged diiron centers in the hydroxylase components of the
      bacterial multicomponent monooxygenases process four substrates during catalysis:
      electrons, protons, dioxygen, and hydrocarbons. Understanding how protein-protein
      interactions mediate the transport of these substrates to the diiron center to
      achieve the selective oxidation of the hydrocarbon is a significant challenge. In
      this Account, we summarize our current knowledge of these processes with a focus
      on the methane monooxygenase system. We also describe recent results for the
      toluene/ o-xylene monooxygenase and phenol hydroxylase systems from Pseudomonas
      sporium OX1. The observation in these latter systems of a diiron(III) oxygenated
      intermediate having different Mossbauer parameters from analogous species in
      other carboxylate-bridged diiron proteins is discussed. The results indicate that
      the ability of the protein framework to tune the reactivity of the diiron center
      at structurally similar active sites is substantially more complex than
      previously recognized.

PMID- 17518436
TI  - Organically modified transition metal alkoxides: chemical problems and structural
      issues on the way to materials syntheses.
AB  - Metal or semimetal alkoxides substituted with nonhydrolyzable organic groups are
      important precursors for inorganic-organic hybrid materials. Understanding the
      chemistry and structural issues of such precursors is a prerequisite for a
      rational materials design. Examples are given in this Account, mainly from the
      chemistry of titanium and zirconium alkoxides, which show that modified metal
      alkoxide precursors sometimes have an unexpected and unpredictable stuctural
      chemistry. Furthermore, chemical consequences of the Lewis acidity of the metal
      alkoxides are discussed, such as adduct formation, ligand exchange reactions, or
      organic side reactions.

PMID- 17518437
TI  - Glycol-modified silanes: novel possibilities for the synthesis of hierarchically
      organized (hybrid) porous materials.
AB  - The preparation of porous hierarchical architectures that have structural
      features spanning from the nanometer to micrometer and even larger dimensions and
      that exhibit certain functionalities is one of the new challenging frontiers in
      materials chemistry. The sol-gel process is one of the most promising synthesis
      routes toward such materials because it not only offers the possibility to
      incorporate organic functions into the porous host but also offers the
      possibility to deliberately tailor the pore structure. In this Account, the
      opportunities given by the application of novel diol-modified silanes are
      discussed for the synthesis of hierarchically organized inorganic and also
      inorganic-organic porous monoliths.

PMID- 17518438
TI  - Dioxygen activation at monovalent nickel.
AB  - The monovalent oxidation state of nickel has received a growing amount of
      attention in recent years, in part due to its suggested catalytic role in a
      number of metalloprotein-mediated transformations. In coordination chemistry,
      nickel(I) is suitable for reductive activation of dioxygen, provided ligands are
      used that stabilize this less common oxidation state against disproportionation
      reactions. Two distinct molecular systems have been explored, which have provided
      access to new nickel-dioxygen structure types, namely, monomeric side-on and end
      on superoxo and trans-micro-1,2-peroxo-dinickel complexes. The geometric and
      electronic structures of the complexes have been established by advanced
      spectroscopic methods, including resonance Raman and X-ray absorption
      spectroscopies, and augmented by density functional theory analyses.

PMID- 17518439
TI  - Porphyrin-retinamides: synthesis and cellular studies.
AB  - A series of four porphyrin-retinamides containing either all-trans- or 13-cis
      retinoid acid residues, directly linked to the para-phenyl position of meso
      tetraphenylporphyrin or via a low-molecular-weight PEG spacer, have been
      synthesized. The biological properties of these conjugates were evaluated in a
      model cell line, human HEp2, and in neuroblastoma SK-N-DZ cells, which exhibit
      moderate expression of retinoic acid receptors and retinoic acid-induced
      differentiation. The directly linked porphyrin-retinamides were taken up by a
      greater extent (20-50% more) in SK-N-DZ than in HEp2 cells. However, the PEG
      containing conjugates accumulated maximally within both cell lines and
      approximately by the same amount, probably due to their increased amphiphilicity.
      Among all conjugates, the porphyrin-PEG-13-cis-retinamide accumulated the most in
      both cell lines (about 5 times more than the non-pegylated conjugates). None of
      the porphyrin-retinamide conjugates were toxic toward HEp2 cells at
      concentrations up to 100 microM, and only the hydrophobic non-pegylated
      conjugates were moderately toxic to SK-N-DZ cells [IC50 (dark) = 56-92 microM,
      and IC50 (at 1 J/cm2) = 6-8 microM]. All conjugates preferentially localized
      within cellular vesicles that correlated well to the lysosomes and, in addition,
      the PEG-containing porphyrin-retinamides were also found in the ER.

PMID- 17518440
TI  - Self-assembling peptide inspired by a barnacle underwater adhesive protein.
AB  - An underwater bioadhesive generally comprises a multiprotein complex that
      provides a molecular basis for self-assembly. We report here a new class of self
      assembling peptide inspired by a 20 kDa barnacle cement protein. Studies on the
      chemically synthesized 24-residue peptide have revealed that (1) it underwent
      irreversible self-assembly upon the addition of salt, (2) the self-assembly was
      started at a salt concentration close to that of seawater with noncovalent
      intermolecular interactions, (3) the self-assembled material resembled a
      macroscopic membrane of interwoven nanofilaments, (4) incubation in an alkaline
      pH range formed the intramolecular disulfide bond of a peptide molecule, thus
      triggering a conformation change of the molecule, and (5) conformational change
      of the building block promoted the formation of a nanofiber, resulting in the
      display of a three-dimensional meshlike mesoscopic structure with defined pores
      having a diameter of approximately 200 nm. The peptide is likely to provide a
      suitable basis for further development of peptide-based materials.

PMID- 17518441
TI  - Preparation of liquid-core nanocapsules from poly[(ethylene oxide)-co-glycidol]
      with multiple hydrophobic linoleates at an oil-water interface and its
      encapsulation of pyrene.
AB  - A convenient approach is provided to prepare liquid-core nanocapsules by cross
      linking an amphiphilic copolymer at an oil-water interface. The hydrophilic
      copolymer poly[(ethylene oxide)-co-glycidol] was prepared by anionic
      polymerization of ethylene oxide and ethoxyethyl glycidyl ether first, then the
      hydroxyl groups on the backbone were recovered after hydrolysis and partly
      modified by hydrophobic conjugated linoleic acid. The copolymer with multiple
      linoleate pendants was absorbed at an oil-water interface and then cross-linked
      to form stable nanocapsules. The mean diameter of the nanocapsule was below 350
      nm, and the size distribution was relatively narrow (<0.2) at low concentrations
      of oil in acetone (<10 mg/mL). The particle size could be tuned easily by
      variation of the emulsification conditions. The nanocapsule was stable in water
      for at least 5 months, and the shell maintained its integrity after removal of
      the oily core by solvent. Pyrene was encapsulated in these nanocapsules, and a
      loading efficiency as high as 94% was measured by UV spectroscopy.

PMID- 17518442
TI  - Influence of the spacer of cationic gemini amphiphiles on the hydration of
      lipoplexes.
AB  - The impact of the length of gemini surfactant spacer on complexation and
      condensation of calf thymus DNA by cationic mixed phospholipid/gemini liposomes
      was investigated by monitoring the conformational changes of DNA by circular
      dichroism and the lipid hydration level by the emission characteristics of the
      fluorescent probe laurdan included in the lipid bilayer. The length of the spacer
      was shown to influence, on one hand, the hydration level and the organization of
      the corresponding liposomes and, on the other, the variation of lipid hydration
      level and the DNA conformation upon complexation. In fact, in correspondence with
      the longest spacer we observed more hydrated liposomes, probably organized in
      domains, a higher extent of dehydration promoted by the addition of DNA, and a
      minor extent of DNA conformational change. The physicochemical features of
      lipoplexes were shown to depend on the [cationic headgroup]/[DNA single base]
      ratio.

PMID- 17518443
TI  - A versatile approach to reducible vinyl polymers via oxidation of telechelic
      polymers prepared by reversible addition fragmentation chain transfer
      polymerization.

PMID- 17518444
TI  - Systematic comparison of bias and precision data obtained with multiple-point and
      one-point calibration in six validated multianalyte assays for quantification of
      drugs in human plasma.
AB  - One-point (linear through zero) calibration is often used as a compromise between
      necessary calibration, workload, and time. The aim of the present study was to
      systematically check the applicability of one-point calibration by comparing bias
      and precision data obtained with full and one-point calibration. Data from
      validation studies of six mass spectrometry-based multianalyte bioanalytical
      assays were used for this purpose. Bias and intermediate precision datasets of
      full multiple-point calibration were compared to six one-point calibration
      datasets (A-F in rising calibrator concentration order) calculated from the same
      raw data. The datasets were statistically compared using the Friedman test
      followed by Dunn's multiple comparison test. The results obtained with full
      calibration and the different one-point calibrations were found to differ
      significantly (P < 0.05) in all of the six studied methods. The best one-point
      calibration results were obtained with calibrator D, with which acceptance
      criteria for bias and precision were fulfilled for the majority of analytes.
      However, some extremely high bias and precision data were obtained for some
      analytes in the low-concentration range. In conclusion, one-point calibration
      with a calibrator close to the center of the full calibration range can be a
      feasible alternative to full calibration.

PMID- 17518445
TI  - Structural analysis of the alpha-2,3-sialyltransferase Cst-I from Campylobacter
      jejuni in apo and substrate-analogue bound forms.
AB  - Sialic acid is an essential sugar in biology that plays key roles in numerous
      cellular processes and interactions. The biosynthesis of sialylated
      glycoconjugates is catalyzed by five distinct families of sialyltransferases. In
      the last 25 years, there has been much research on the enzymes themselves, their
      genes, and their reaction products, but we still do not know the precise
      molecular mechanism of action for this class of glycosyltransferase. We
      previously reported the first detailed structural and kinetic characterization of
      Cst-II, a bifunctional sialyltransferase (CAZy GT-42) from the bacterium
      Campylobacter jejuni [Chiu et al. (2004) Nat. Struct. Mol. Biol. 11, 163-170].
      This enzyme can use both Gal-beta-1,3/4-R and Neu5Ac-alpha-2,3-Gal-beta-1,3/4-R
      as acceptor sugars. A second sialyltransferase from this bacterium, Cst-I, has
      been shown to utilize solely Gal-beta-1,3/4-R as the acceptor sugar in its
      transferase reaction. We report here the structural and kinetic characterization
      of this monofunctional enzyme, which belongs to the same sialyltransferase family
      as Cst-II, in both apo and substrate bound form. Our structural data show that
      Cst-I adopts a similar GTA-type glycosyltransferase fold to that of the
      bifunctional Cst-II, with conservation of several key noncharged catalytic
      residues. Significant differences are found, however, between the two enzymes in
      the lid domain region, which is critical to the creation of the acceptor sugar
      binding site. Furthermore, molecular modeling of various acceptor sugars within
      the active sites of these enzymes provides significant new insights into the
      structural basis for substrate specificities within this biologically important
      enzyme class.

PMID- 17518446
TI  - Mutational analysis of active site residues in the Staphylococcus aureus
      transpeptidase SrtA.
AB  - In Staphylococcus aureus, virulence and colonization-associated surface proteins
      are covalently anchored to the cell wall by the transpeptidase Sortase A (SrtA).
      In order to better understand the contribution of specific active site residues
      to substrate recognition and catalysis, we performed mutational analysis of
      several key residues in the SrtA active site. Analysis of protein stability,
      kinetic parameters, solvent isotope effects, and pH-rate profiles for key SrtA
      variants are consistent with a reverse protonated Cys184-His120 catalytic dyad,
      and implicate a role for Arg197 in formation of an oxyanion hole to stabilize the
      transition state. In contrast, mutation of Asp185 and Asp186 produced negligible
      effects on catalysis, and no evidence was found to support the existence of a
      functional catalytic triad. Mutation of Thr180, Leu181, and Ile182 to alanine
      produced modest decreases in SrtA activity and led to substrate inhibition.
      Thermodynamic stability measurements by SUPREX (stability of unpurified proteins
      from rates of H/D exchange) revealed decreases in conformational stability that
      correlate with the observed substrate inhibition for each variant, signifying a
      potential role for the conserved 180TLITC184 motif in defining the active-site
      architecture of SrtA. In contrast, mutation of Thr183 to alanine led to a
      significant 1200-fold decrease in kcat, which appears to be unrelated to
      conformational stability. Potential explanations for these results are discussed,
      and a revised model for SrtA catalysis is presented.

PMID- 17518447
TI  - Charge-transfer controlled exchange interaction in radical-triplet encounter
      pairs as studied by FT-EPR spectroscopy.
AB  - The exchange interaction, J, producing quartet and doublet energy separation in
      radical-triplet excited molecule encounter pairs, was investigated in solution by
      measuring chemically induced dynamic electron polarization (CIDEP) created
      through the radical-triplet pair mechanism. A time-resolved FT-EPR method was
      utilized to measure CIDEP of galvinoxyl radical by recording FID signals and an
      absolute magnitude of CIDEP, P(n), was determined for each radical-triplet system
      by detailed analysis of the time evolution curves of CIDEP. A transient FT-EPR
      signal phase remarkably depends on the triplet molecule. The signal phase is
      related to the sign of J value, which is responsible for the radical-triplet pair
      interaction. Most of galvinoxyl-triplet systems showed normal negative sign. An
      unusual positive sign was found in some systems characterized by a small energy
      gap, DeltaG, between the radical-triplet pair and intermolecular charge transfer
      (CT) states. A theoretical calculation of J value for radical-triplet encounter
      pairs was carried out by considering exchange integral and intermolecular CT
      interaction. According to the calculated J value and the diffusion theory for
      CIDEP magnitude, experimental Pn values were theoretically reproduced as a
      function of DeltaG. The present results confirm our previously reported CT model
      explaining the complicated nature of the sign of J value in the galvinoxyl
      triplet encounter pairs. According to the proposed model for CT effect on J value
      and CIDEP results, nature of J value in radical-triplet pairs is discussed.

PMID- 17518448
TI  - Interaction between water molecules and zinc sulfide nanoparticles studied by
      temperature-programmed desorption and molecular dynamics simulations.
AB  - We have investigated the bonding of water molecules to the surfaces of ZnS
      nanoparticles (approximately 2-3 nm sphalerite) using temperature-programmed
      desorption (TPD). The activation energy for water desorption was derived as a
      function of the surface coverage through kinetic modeling of the experimental TPD
      curves. The binding energy of water equals the activation energy of desorption if
      it is assumed that the activation energy for adsorption is nearly zero. Molecular
      dynamics (MD) simulations of water adsorption on 3 and 5 nm sphalerite
      nanoparticles provided insights into the adsorption process and water binding at
      the atomic level. Water binds with the ZnS nanoparticle surface mainly via
      formation of Zn-O bonds. As compared with bulk ZnS crystals, ZnS nanoparticles
      can adsorb more water molecules per unit surface area due to the greatly
      increased curvature, which increases the distance between adjacent adsorbed
      molecules. Results from both TPD and MD show that the water binding energy
      increases with decreasing the water surface coverage. We attribute the increase
      in binding energy with decreasing surface water coverage to the increasing degree
      of surface under-coordination as removal of water molecules proceeds. MD also
      suggests that the water binding energy increases with decreasing particle size
      due to the further distance and hence lower interaction between adsorbed water
      molecules on highly curved smaller particle surfaces. Results also show that the
      binding energy, and thus the strength of interaction of water, is highest in
      isolated nanoparticles, lower in nanoparticle aggregates, and lowest in bulk
      crystals. Given that water binding is driven by surface energy reduction, we
      attribute the decreased binding energy for aggregated as compared to isolated
      particles to the decrease in surface energy that occurs as the result of inter
      particle interactions.

PMID- 17518449
TI  - Temperature dependence of excited state proton transfer in ice.
AB  - We have studied the excited-state proton-transfer rate of four photoacids in ice
      as a function of temperature. For all four photoacids, we have found a non
      Arrhenius behavior of the proton-transfer rate constant, k(PT). d(ln
      k(PT))/d(1/T) decreases as the temperature decreases. The average slope of
      ln(k(PT))versus 1/T depends on the photoacid strength (pK*). The stronger the
      photoacid is, the smaller the slope. For the strongest photoacid 2-naphthol-6,8
      disulfonate (2N68DS) the largest slope is 35 kJ/mol at about 270 K, and the
      smallest measured slope is about 8 kJ/mol at about 215 K. We propose that the
      temperature dependence of k(PT) in ice at the temperature range 270 > T > 200 K
      can be explained as arising from contributions of two proton-transfer mechanisms
      over the barrier and tunneling under the barrier. At very low temperatures T <
      200 K, the slope of ln(k(PT)) versus 1/T increases again. At about 170 K, the
      proton-transfer rate is much slower than the radiative rate, and the deprotonated
      form of the photoacid cannot be detected in the steady-state emission spectrum.
      At lower temperatures, T < 200 K, the rate further decreases because of a
      limitation on the reaction caused by the restrictions on the H2O hydrogen
      reorientations.

PMID- 17518450
TI  - Combined ESR and thermodynamic studies of the superoxide adduct of 5
      (diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO): hindered rotation
      around the O-O bond evidenced by two-dimensional simulation of temperature
      dependent spectra.
AB  - Experiments were performed to elucidate the origin of the superhyperfine
      structure and line width alternation (LWA) seen in the ESR spectrum of the major
      diastereoisomer (1) of DEPMPO-OOH, the remarkably persistent superoxide adduct of
      5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO). Using selectively
      deuterated DEPMPO derivatives, we demonstrated that the superhyperfine pattern
      can be unambiguously attributed to long-range couplings. The recording in
      pyridine of highly resolved spectra in a wide temperature range, combined with
      two-dimensional simulation, allowed us to characterize an inverted LWA in 1 and
      revealed a uniform line broadening in the spectrum of the minor DEPMPO-OOH
      diastereoisomer (2), with both effects originating from a chemical exchange
      between conformers. When the individual spectra of 1 presenting LWA in the fast
      exchange regime were simulated, four equally good fits were obtained and this
      ambiguity could be resolved by using a two-dimensional simulation technique. The
      thermodynamic and kinetic constants of this exchange were consistent with a
      rotation around the O-O bond. We propose that line broadening effects in 1 and 2
      result from this O-O rotation concerted with the pseudo-rotation of the
      pyrrolidine ring.

PMID- 17518451
TI  - High-resolution infrared spectroscopy of HCN-Agn (n = 1-4) complexes solvated in
      superfluid helium droplets.
AB  - High-resolution infrared spectroscopy has been used to determine the structures,
      C-H stretching frequencies, and dipole moments of the HCN-Agn (n = 1-3) complexes
      formed in superfluid helium droplets. The HCN-Ag4 cluster was tentatively
      assigned based upon pick-up cell pressure dependencies and harmonic vibrational
      shift calculations. Ab initio and density functional theory calculations were
      used in conjunction with the high-resolution spectra to analyze the bonding
      nature of each cluster. All monoligated species reported here are bound through
      the nitrogen end of the HCN molecule. The HCN-Agn complexes are structurally
      similar to the previously reported HCN-Cun clusters, with the exception of the
      HCN-Ag binary complex. Although the interaction between the HCN and the Agn
      clusters follows the same trends as the HCN-Cun clusters, the more diffuse nature
      of the electrons surrounding the silver atoms results in a much weaker
      interaction.

PMID- 17518452
TI  - Comparison of interfacial electron transfer through carboxylate and phosphonate
      anchoring groups.
AB  - The effects of anchoring groups on electron injection from adsorbate to
      nanocrystalline thin films were investigated by comparing injection kinetics
      through carboxylate versus phosphonate groups to TiO2 and SnO2. In the first pair
      of molecules, Re(LA)(CO)3Cl (ReC1A) and Re(Lp)(CO)3Cl (ReC1P), [LA=2,2'
      bipyridine-4,4'-bis-CH2-COOH, Lp=2,2'-bipyridine-4,4'-bis-CH2-PO3H2], the
      anchoring groups were insulated from the bipyridine ligand by a CH2 group. In the
      second pair of molecules, Ru(dcbpyH2)2(NCS)2 (RuN3) and Ru(bpbpyH2)2(NCS)2
      (RuN3P), [dcbpy=2,2'-bipyridine-4,4'-biscarboxylic acid, bpbpy=2,2'-bipyridine
      4,4'-bisphosphonic acid], the anchoring groups were directly connected to the
      bipyridine ligands. The injection kinetics, as measured by subpicosecond IR
      absorption spectroscopy, showed that electron injection rates from ReC1P to both
      TiO2 and SnO2 were faster than those from ReC1A. The injection rates from RuN3
      and RuN3P to SnO2 films were similar. On TiO2, the injection kinetics from RuN3
      and RuN3P were biphasic: carboxylate group enhances the rate of the <100 fs
      component, but reduces the rate of the slower components. To provide insight into
      the effect of the anchoring groups, the electronic structures of Re-bipyridyl-Ti
      model clusters containing carboxylate and phosphonate anchoring groups and with
      and without a CH2 spacer were computed using density functional theory. With the
      CH2 spacer, the phosphonate group led to a stronger electronic coupling between
      bpy and Ti center than the carboxylate group, which accounted for the faster
      injection from ReC1P than ReC1A. When the anchoring groups were directly
      connected to the bpy ligand without the CH2 spacer, such as in RuN3 and RuN3P,
      their effects were 2-fold: the carboxylate group enhanced the electronic coupling
      of bpy pi* with TiO2 and lowered the energy of the bpy orbital. How these
      competing factors led to different effects on TiO2 and SnO2 and on different
      components of the biphasic injection kinetics were discussed.

PMID- 17518453
TI  - A group additivity algorithm for polychlorinated dibenzofurans derived from
      selected DFT analyses.
AB  - The difficulty in measuring the heats of combustion of polychlorinated
      dibenzofurans (PCDFs) has resulted in a shortage of data on their heats of
      formation, required for the purpose of developing an understanding of the role of
      thermodynamics and kinetics in their production via industrial processes. B3LYP
      density functional theory calculations have been carried out on a number of PCDFs
      using 6-31G(d) and 6-311+G(3df,p) basis sets to estimate their heats of formation
      based on the known experimental values for dibenzofuran, benzene and
      chlorobenzene. By examining the interactions among chlorine substituents, it is
      shown that energy contributions arising from successive chlorination can be
      interpreted in a predictable way, based on a small number of key energy
      parameters associated with ring position and chlorine atom repulsions. These
      parameters have been presented as the basis for a simplified prediction
      algorithm, which can be used to reproduce the predicted DFT heat of formation to
      within a few kJ/mol, avoiding the need to carry out extensive DFT calculations on
      the possible 135 isomers of the dibenzofuran group.

PMID- 17518454
TI  - Didehydrophenanthrenes: structure, singlet-triplet splitting, and aromaticity.
AB  - In this work, we explore the geometries, relative stabilities, singlet-triplet (S
      T) splittings, and local aromaticities of the 25 possible didehydrophenanthrenes
      (DDPs) at the BLYP/6-31G(d) level. The main aim is to understand their molecular
      structure and stability in terms of the electronic structure. To this end, we
      analyze the changes induced by didehydrogenation in molecular structure and local
      aromaticity and we investigate the coupling strength between radical centers in
      DDPs through the evaluation of S-T splittings. Further evidence for the repulsive
      character of the H-H interactions in phenanthrene's bay region is gained from the
      relative energies of the triplet states of the different DDPs.

PMID- 17518455
TI  - The 1,2,3-tridehydrobenzene triradical: 2B or not 2B? The answer is 2A!
AB  - The molecular and electronic structure of 1,2,3-tridehydrobenzene was
      investigated by a variety of computational methods. The two lowest electronic
      states of the triradical are the (2)B(2) and (2)A(1) doublet states characterized
      by different interactions of the unpaired electrons. Vertically, the two states
      are well separated in energy-by 4.9 and 1.4 eV, respectively. However, due to
      different bonding patterns, their equilibrium structures are very different and,
      adiabatically, the two states are nearly degenerate. The adiabatic energy gap
      between the (2)B(2) and (2)A(1) states is estimated to be 0.7-2.1 kcal/mol, in
      favor of the (2)A(1) state. Harmonic vibrational frequencies and anharmonic
      corrections were calculated for both states. Comparison with the three
      experimentally observed IR transitions supports the assignment of the (2)A(1)
      ground state for the triradical with a weakly bonding distance of 1.67-1.69 A
      between the meta radical centers.

PMID- 17518456
TI  - Structures of small Li(NH3)n and Li(NH3)n+ clusters (n = 1-5): evidence from
      combined photoionization efficiency measurements and ab initio calculations.
AB  - Photoionization threshold measurements have been carried out for small Li(NH3)n
      clusters (n = 1-5) and have been combined with ab initio calculations to
      determine structural information. The calculated adiabatic ionization energy for
      the lowest-energy isomer of each cluster is found to be in excellent agreement
      with the corresponding experimental photoionization threshold, providing evidence
      that the calculated structures are correct. The combination of the
      photoionization efficiency curve and the calculated adiabatic ionization energies
      also confirms the tentative assignment of the infrared spectrum of Li(NH3)4
      reported by Salter and co-workers (J. Chem. Phys. 2006, 125, 34302); i.e., the 3
      + 1 isomer does not contribute and the spectrum is due solely to the 4 + 0
      isomer. The findings are consistent with an inner solvation shell that can hold a
      maximum of four ammonia molecules around the central lithium atom.

PMID- 17518457
TI  - Gauge-origin-independent coupled cluster singles and doubles calculation of
      magnetic circular dichroism of azabenzenes and phosphabenzene using London
      orbitals.
AB  - A computational study of the Faraday B term of magnetic circular dichroism at the
      coupled cluster singles and doubles level is presented for pyridine, pyrazine,
      pyrimidine, and phosphabenzene. Gauge-origin independence is obtained by
      expressing the B term as a total derivative of the one-photon dipole transition
      strength and using London orbitals. The high quality of the coupled cluster
      singles and doubles (CCSD) B terms makes these useful for the assignment of
      experimental spectra. Previous assignments of the experimental spectra based on
      the qualitative perimeter model are confirmed by the CCSD results for the three
      azines, while a reassignment is proposed for phosphabenzene. For non-overlapping
      bands, the B terms calculated at the equilibrium geometries are in good agreement
      with the experimental values. For overlapping bands, large deviations occur.
      Attributing a line width to the calculated equilibrium B terms leads to a large
      cancellation of positive and negative contributions. This cancellation may result
      in a large displacement of the band center maximum, leading to a large
      uncertainty in the assignments of "vertical experimental excitation energies"
      (pyridine). Bands may also completely vanish due to such cancellation
      (phosphabenzene). Explicit consideration of the cancellation yields simulated
      theoretical spectra that are in good agreement with experiment once the
      theoretical spectra are parallel displaced. A major contribution for this
      parallel displacement is the shift in the excitation energies due to correlation
      beyond CCSD, as seen when comparing vertical CCSD and CC3 equilibrium-geometry
      excitation energies.

PMID- 17518458
TI  - Hyperspectral infrared imaging of HF(v, J) chemiluminescence and gain in
      chemically reacting flowfields.
AB  - This paper presents results from investigations of chemically reacting flowfields
      and optical gain profiles in HF chemical laser media by infrared hyperspectral
      imaging. Subsonic and supersonic chemiluminescent F+H2 reacting flowfields,
      produced in high-fluence microwave-driven reactors, were imaged at a series of
      wavelengths, 2.6-3.1 microm, by a low-order, spectrally scanning Fabry-Perot
      interferometer mated to an infrared camera. The resulting hyperspectral data
      cubes define the spectral and spatial distributions of the emission. Spectrally
      resolved images at high spatial resolution were processed to determine spatial
      distributions of the excited-state concentrations of the product HF(v, J)
      molecules, as well as spatial distributions of small-signal gain on specific
      laser transitions. Additional high-resolution Fourier transform spectroscopy and
      spectral fitting analysis determined detailed excited-state distributions in the
      reacting flowfields. The measurements showed that energetic HF(v, J) state
      distributions were generated by both the supersonic and fast-flow subsonic mixing
      schemes. In particular, the subsonic reactor produced a spatially distributed
      field of inverted, near-nascent state populations, with small-signal gains near 2
      3%/cm.

PMID- 17518459
TI  - 5-alkynyl analogs of arabinouridine and 2'-deoxyuridine: cytostatic activity
      against herpes simplex virus and varicella-zoster thymidine kinase gene
      transfected cells.
AB  - A group of arabinouridines (TMSEAU, EAU, IEAU-TA) and 2'-deoxyuridines (TMSEDU,
      EDU, IEDU) having a variety of substituents at the uracil C-5 position
      (trimethylsilylethynyl, TMSE; ethynyl, E; or iodoethynyl, IE), and the sugar C-2'
      position (2'-arabino OH in arabinouridine, AU; or 2'-deoxyribo H in 2'
      deoxyuridine, DU) were prepared to acquire antiviral structure-activity
      relationships. A broad-spectrum viral panel screen showed that these 5
      alkynylarabino/deoxy-uridines exhibit moderate anti-HSV-1 activity, with no
      difference in potency between arabinouridines and 2'-deoxyuridines. The 2'
      deoxyuridines TMSEDU, EDU, and IEDU, unlike the arabinouridines, exhibited potent
      antiviral activity against cytomegalovirus, but they were also highly cytostatic.
      The abilities of the 5-alkynylarabino/deoxy-uridines to inhibit nontransfected
      (wild-type or thymidine kinase-deficient, tk-) and viral gene transfected (HSV-1,
      HSV-2, or VZV thymidine kinase-positive, tk+) FM3A and OST (osteosarcoma) cells
      were determined. This group of 5-alkynylarabino/deoxy-uridines showed an enhanced
      ability to inhibit cells transfected with a viral thymidine kinase gene (HSV
      1tk+, HSV-2tk+, VZVtk+) relative to wild-type or thymidine kinase-deficient (tk-)
      cells.

PMID- 17518460
TI  - DNA minor groove pharmacophores describing sequence specific properties.
AB  - The more that is known about human and other genome sequences and the correlation
      between gene expression and the course of a disease, the more evident it seems to
      be that DNA is chosen as a drug target instead of proteins which are built with
      the information encoded by DNA. According to this approach, small minor groove
      binding molecules have been designed to bind the DNA sequence specifically and
      thereby downregulate genes. Because of their lack of druglikeness, we plan to use
      them as templates for forthcoming virtual screening experiments to discover
      molecules with the same bioactivity and a different scaffold. In this proof of
      principle study, carried out with the software tool Catalyst, we present a model
      work for description of a ligand-DNA complex with the aid of pharmacophore
      modeling methods. The successful reproduction of sequence specificity of a
      polyamidic minor groove binding ligand is the precondition for later model
      application to virtual screening.

PMID- 17518461
TI  - Rapid estimation of relative protein-ligand binding affinities using a high
      throughput version of MM-PBSA.
AB  - By employing a modified protocol of the Molecular Mechanics with Poisson
      Boltzmann Surface Area (MM-PBSA) methodology we substantially decrease the
      required computation time for calculating relative estimates of protein-ligand
      binding affinities. The modified method uses a generalized Born implicit
      solvation model during molecular dynamics to enhance conformational sampling as
      well as a very efficient Poisson-Boltzmann solver and a computational design
      based on a distributed-computing paradigm. This construction allows for reduction
      of the computational cost of the calculations by roughly 2 orders of magnitude
      compared to the traditional formulation of MM-PBSA. With this high-throughput
      version of MM-PBSA we show that one can produce efficient physics-based estimates
      of relative binding free energies with reasonable correlation to experimental
      data and a total computation time that is sufficiently low such that an
      industrially relevant throughput can be realized given currently accessible
      computing resources. We demonstrate this approach by performing a comparison of
      different MM-PBSA implementations on a set of 18 ligands for the protein target
      urokinase.

PMID- 17518462
TI  - ThermoData Engine (TDE): software implementation of the dynamic data evaluation
      concept. 2. Equations of state on demand and dynamic updates over the web.
AB  - ThermoData Engine (TDE) is the first full-scale software implementation of the
      dynamic data evaluation concept, as reported recently in this journal. The
      present paper describes two major software enhancements to TDE: (1) generation of
      equation of state (EOS) representations on demand and (2) establishment of a
      dynamically updated experimental data resource for use in the critical evaluation
      process. Four EOS formulations have been implemented in TDE for on-demand
      evaluation: the volume translated Peng-Robinson, modified Sanchez-Lacombe, PC
      SAFT, and Span Wagner EOS. The equations are fully described with their general
      application. The class structure of the program is described with particular
      emphasis on special features required to implement an equation, such as an EOS,
      that represents multiple properties simultaneously. Full implementation of the
      dynamic data evaluation concept requires that evaluations be based on an up-to
      date "body of knowledge" or, in the case of TDE, an up-to-date collection of
      experimental results. A method to provide updates through the World Wide Web is
      described that meets the challenges of maintenance of data integrity with full
      traceability. Directions for future enhancements are outlined.

PMID- 17518463
TI  - Remarkable changes in the optical properties of CeO(2) nanocrystals induced by
      lanthanide ions doping.
AB  - Highly uniform and well-dispersed CeO(2) and CeO(2):Eu(3+) (Sm(3+), Tb(3+))
      nanocrystals were prepared by a nonhydrolytic solution route and characterized by
      X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray
      photoelectron spectra (XPS), UV/vis absorption, and photoluminescence (PL)
      spectra, respectively. The result of XRD indicates that the CeO(2) nanocrystals
      are well crystallized with a cubic structure. The TEM images illustrate that the
      average size of CeO(2) nanocrystals is about 3.5 nm in diameter. The absorption
      spectrum of CeO(2):Eu(3+) nanocrystals exhibits red-shifting with respect to that
      of the undoped CeO(2) nanocrystals. Under the excitation of 440 nm (or 426 nm)
      light, the colloidal solution of the undoped CeO(2) nanocrystals shows a very
      weak emission band with a maximum at 501 nm, which is remarkably enhanced by
      doping additional lanthanide ions (Eu(3+), Tb(3+), Sm(3+)) in the CeO(2)
      nanocrystals. The emission band is not due to the characteristic emission of the
      lanthanide ions but might arise from the oxygen vacancy which is introduced in
      the fluorite lattice of the CeO(2)nanocrystals to compensate the effective
      negative charge associated with the trivalent ions.

PMID- 17518464
TI  - Tetrairon and hexairon hydroxo/acetato clusters stabilized by multiple
      polyoxometalate scaffolds. Structures, magnetic properties, and chemistry of a
      dimer and a trimer.
AB  - Investigation of the catalytically relevant gamma-diiron(III) Keggin complexes in
      aqueous acetate buffer leads to a dimeric C(2v)-symmetric polyanion,
      [{Fe(OH)(OAc)}(4)(gamma-SiW(10)O(36))(2)](12-) (3) and a trimeric C(2)-symmetric
      polyanion, [{Fe(6)(OH)(9)(H(2)O)(2)(OAc)(2)}(gamma-SiW(10)O(36))(3)](17-) (4).
      Polyanion 3 incorporates a hydroxo/acetato-bridged tetrairon(III) core, while 4
      incorporates a trigonal prismatic hydroxo/acetato-bridged hexairon(III) core. The
      monomeric building unit of 3 and 4, {gamma-SiW(10)Fe(2)}, adopts the "out-of
      pocket" structural motif (with two corner-sharing FeO(6) coordination polyhedra
      no longer connected to the internal SiO(4) tetrahedron of the Keggin unit) also
      observed in the {gamma-SiW(10)Fe(2)}(-)type structures isolated from nonbuffered
      aqueous solutions. Following hydrolysis, 3 is converted to 4 as confirmed by
      (29)Si NMR. Magnetic measurements establish that in both 3 and 4 all exchange
      interactions are antiferromagnetic.

PMID- 17518465
TI  - Conformational indeterminism in protein misfolding: chiral amplification on
      amyloidogenic pathway of insulin.
AB  - Unlike folding, protein aggregation is a multipathway, kinetically controlled
      process yielding different conformations of fibrils. The dynamics and
      determinism/indeterminism boundaries of misfolded conformations remain obscure.
      Here we show that, upon vortexing, insulin forms two distinct types of fibrils
      with opposite local chiral preferences, which manifest in the opposite twists of
      bound dye, thioflavin T. Occurrence of either type of fibrils in a test tube is
      only stochastically determined. By acting through an autocatalytic, "chiral
      amplification"-like mechanism, a random conformational fluctuation triggers
      conversion of the macroscopic amount of insulin into aggregates with uniformly
      biased chiral moieties, which bind and twist likewise the achiral dye. Although a
      convection-driven chiral amplification in achiral systems, which results in
      randomly distributed excesses of optically active forms, is known, observation of
      such a phenomenon in misfolded protein built of l-amino acids is unprecedented.
      The two optical variants of insulin fibrils show distinct morphologies and can
      propagate their chiral biases upon seeding to nonagitated insulin solutions. Our
      findings point to a new aspect of topological complexity of protein fibrils: a
      chiral feature of hierarchically assembled polypeptides, which is partly
      emancipated from the innate left-handedness of amino acids. Because altering
      chirality of a molecule changes dramatically its biological activity, the finding
      may have important ramifications in the context of the structural basis of
      "amyloid strains".

PMID- 17518466
TI  - Beyond exciton theory: a time-dependent DFT and Franck-Condon study of perylene
      diimide and its chromophoric dimer.
AB  - The diimide perylene motif exhibits a dramatic intensity reversal between the 0 -
      > 0 and 0 --> 1 vibronic bands upon pi-pi stacking; this distinct spectral
      property has previously been used to measure folding dynamics in covalently bound
      oligomers and synthetic biological hybrid foldamers. It is also used as a tool to
      assess organization of the pi-stacking, indicating the presence of H- or J
      aggregation. The zeroth-order exciton model, often used to describe the optical
      properties of chromophoric aggregates, is solely a transition dipole coupling
      scheme, which ignores the explicit electronic structure of the system as well as
      vibrational coupling to the electronic transition. We have therefore examined the
      optical properties of gas-phase perylene tetracarboxylic diimide (PTCDI) and its
      chromophoric dimer as a function of conformation to relate the excited-state
      distributions predicted by exciton theory with that of time-dependent density
      functional theory (TDDFT). Using ground- and excited-state geometries, the Franck
      Condon (FC) factors for the lowest energy molecular nature electronic transition
      have been calculated and the origin of the intensity reversal of 0 --> 0 and 0 -
      > 1 vibronic bands has been proposed.

PMID- 17518468
TI  - Cocktails of Tb(3+) and Eu(3+) complexes: a general platform for the design of
      ratiometric optical probes.
AB  - Fluorescent and luminescent reporters that signal molecular events of interest by
      modulating the ratio of peaks in their emission profile have advantages over
      reporters that simply modulate their emission intensity, since ratiometric
      measurement is concentration-independent and allows them to be effective in
      complex contexts, such as living cells or sensor microarrays. We herein describe
      a general platform for the design of ratiometric probes based on a heterometallic
      Tb(3+)/Eu(3+) bis-lanthanide ensemble, consisting of a mixture, or "cocktail", of
      otherwise identical heterometalated chelates. The chelate contains an organic
      photon antenna that sensitizes the Tb(3+)/Eu(3+) luminescence. The contributions
      of the two metals to the composite luminescence spectrum can be tuned to the same
      relative scale by adjusting the stoichiometry of the cocktail, allowing subtle
      changes in their ratio to be accurately measured. Importantly, the ratio responds
      to chemical and environmental changes experienced by the photon antenna, making
      the system an ideal platform for the design of chemical and enzymatic probes. As
      proofs of concept, we describe a ratiometric probe for esterase activity and a
      polarity-responsive ratiometric sensor.

PMID- 17518469
TI  - An unprecedented Fe(III)(mu-OH)Zn(II) complex that mimics the structural and
      functional properties of purple acid phosphatases.

PMID- 17518473
TI  - Chromogenic signaling of hydrogen carbonate anion with pyrylium-containing
      polymers.
AB  - Polymeric films containing pyrylium derivatives showing a selective color
      modulation from yellow to red in the presence of the poorly coordinating hydrogen
      carbonate anion in water at neutral pH have been developed.

PMID- 17518474
TI  - Organocatalytic synthesis of (2S,3R)-3-hydroxy-3-methyl-proline (OHMePro), a
      component of polyoxypeptins, and relatives using OHMePro itself as a catalyst.
AB  - An efficient synthesis of (2S,3R)-3-hydroxy-3-methylproline (OHMePro), a
      component of polyoxypeptins, and relatives was achieved, in which an
      intramolecular asymmetric aldol reaction of the ketoaldehyde using OHMePro itself
      as an organocatalyst constitutes a key step.

PMID- 17518475
TI  - Cobalt-rhodium heterobimetallic nanoparticle-catalyzed synthesis of alpha,beta
      unsaturated amides from internal alkynes, amines, and carbon monoxide.
AB  - The first example of cobalt-rhodium heterobimetallic nanoparticle-catalyzed
      synthesis of alkenyl amides from alkynes, amines, and carbon monoxide is
      described.

PMID- 17518476
TI  - Solid-phase synthesis of carboxylic and oxamic acids via OsO4/NaIO4/HMTA-mediated
      oxidative cleavage of acetylenic peptides.
AB  - A general method for the solid-phase synthesis of carboxy-functionalized peptides
      by oxidative cleavage of alkynes is presented. Clean and quantitative conversion
      is enabled by the addition of bases, such as DABCO and HMTA, to the classical
      OsO4/NaIO4 mixture. The utility of the reaction is further illustrated by the
      synthesis of oxamic acids.

PMID- 17518477
TI  - Asymmetric synthesis of 6-alkyl- and 6-arylpiperidin-2-ones. Enantioselective
      synthesis of (S)-(+)-coniine.
AB  - A variety of diolefinic hydrazides (1) have been assembled in a highly
      diastereoselective manner by addition of allyllithium to chiral SAMP hydrazones
      followed by N-acylation with acryloyl chloride. Substrates 1 undergo ring-closing
      metathesis to give the cyclic enehydrazides (5) which can be easily converted
      into virtually enantiopure 6-alkyl- or 6-arylpiperidin-2-ones (7). The
      versatility of this hydrazone addition-RCM protocol has been further exemplified
      by the conversion of the unsaturated heterocycle 5b into the piperidine alkaloid
      (S)-(+)-coniine.

PMID- 17518478
TI  - A highly alpha-regioselective AgOTf-catalyzed nucleophilic substitution of the
      Baylis-Hillman acetates with indoles.
AB  - An efficient method for highly alpha-regioselective nucleophilic substitution of
      the Baylis-Hillman acetates with indoles catalyzed by AgOTf in high yields (72
      99%) has been developed. Reductive cyclization of the substitution products
      furnished the azepinoindole derivatives in good yields (up to 93%).

PMID- 17518479
TI  - Synthesis of meso-5-azaindolyl-appended Zn(II) porphyrins via Pd-catalyzed
      annulation.
AB  - Pd-catalyzed annulation reaction of meso-hexynyl Zn(II) porphyrin with 4-amino-3
      iodopyridine efficiently provides meso-3-(5-azaindolyl)-substituted Zn(II)
      porphyrin as a major product, which assembles to form a slipped cofacial dimer by
      the complementary coordination of the pyridine moiety to the Zn(II) center. 2
      iodoaniline and 2-iodophenol also undergo this [3 + 2] annulation with the meso
      hexynyl Zn(II) porphyrin to furnish meso-indolyl- and benzofuranyl-substituted
      Zn(II) porphyrins, respectively.

PMID- 17518480
TI  - Asymmetric hydrogenation of alpha-hydroxy ketones catalyzed by MsDPEN-Cp*Ir(III)
      complex.
AB  - Asymmetric hydrogenation of a series of alpha-hydroxy aromatic ketones in
      methanol catalyzed by Cp*Ir(OTf)(MsDPEN) (MsDPEN = N-(methanesulfonyl)-1,2
      diphenylethylenediamine) affords the 1-aryl-1,2-ethanediols in up to 99% ee. The
      reaction can be conducted with a substrate-to-catalyst molar ratio as high as
      6000 under 10 atm of H2. 1-hydroxy-2-propanone is also hydrogenated with high
      enantioselectivity.

PMID- 17518481
TI  - Highly enantioselective organocatalytic direct aldol reaction in an aqueous
      medium.
AB  - We have demonstrated that small organic molecules 1 and 2 catalyzed the direct
      aldol reaction of both acyclic and cyclic ketones with different aldehydes in an
      excess of water/brine. Excellent enantioselectivities up to >99% and
      diastereoselectivities up to 99% with very good yields were obtained by using
      much lower catalyst loadings (0.5 mol %).

PMID- 17518482
TI  - Characterization of adducts formed in the reaction of glutaraldehyde with 2'
      deoxyadenosine.
AB  - Glutaraldehyde (1,5-pentanedial) is a widely used industrial chemical that has
      been found to be mutagenic in bacteria and mammalian cells. In this study, we
      examined the reaction of glutaraldehyde with 2'-deoxyadenosine and calf thymus
      DNA in aqueous buffered solutions. The 2'-deoxyadenosine adducts were isolated by
      reversed phase HPLC and characterized by their UV absorbance and 1H and 13C NMR
      spectroscopic and mass spectrometric features. The reaction produced three major
      adducts. The adduct dA567 was derived from two 2'-deoxyadenosine units bound
      together with a piperidine unit, and its yield was 10.4%. The carbons of the
      piperidine ring originated from glutaraldehyde, whereas the nitrogen of the ring
      originated from the exocyclic amino group of one of the 2'-deoxyadenosine units.
      The adduct dA451d (yield 0.6%) was similar in structure to dA567, but one of the
      deoxyribose moieties from 2'-deoxyadenosine was missing. The third adduct, dA334,
      consisted of a hydroxy-tetrahydropyridine moiety derived from glutaraldehyde and
      N6 of 2'-deoxyadenosine (yield 4.0%). Furthermore, LC-ESI-MS/MS analysis of the
      reaction mixture revealed the formation of compounds with ion peaks of m/z = 352.
      None of these compounds were sufficiently stable for preparative isolation. They
      were tentatively identified as a pair of diastereomers of 2,6-dihydroxypiperidine
      derivatives, which are likely precursors to dA334. Plausible mechanisms for the
      formation of the adducts are presented. In the reaction of glutaraldehyde with
      single and double stranded calf thymus DNA, the dA334 adduct was formed.

PMID- 17518483
TI  - Influence of cyclohexane vapor on stick-slip friction between mica surfaces.
AB  - Stick-slip friction between mica surfaces under cyclohexane vapor has been
      investigated with the Surface Force Apparatus. The dynamic shear stress decreased
      from 60 to 10 MPa with increasing relative vapor pressure (rvp) from 5% to 50%.
      Between a rvp of 50% and 80%, the shear stress remained at approximately 10 MPa,
      with a slight decrease on increasing the rvp. At a rvp greater than 80%, the
      values of shear stress were below 5 MPa. The stick-slip behavior was observed in
      the rvp range of 20% to saturation. When the rvp reached 20%, stick-slip appeared
      but faded out with sliding time. At a rvp greater than 50%, the stick-slip
      pattern was stable without fading. By taking into account the size of the
      meniscus formed by capillary condensation of the liquid around the contact area
      and the Laplace pressure, the dependence of shear stress and the stick-slip
      modulation on rvp suggests that the origin of the stick-slip observed in
      cyclohexane vapor is as follows: At a rvp greater than 50%, where stable sick
      slip is observed, the stick-slip caused by the cyclohexane layering in the
      contact area is of essentially the same origin as that observed with mica
      surfaces sliding in bulk cyclohexane liquid. As with the bulk liquid experiment,
      decreasing the layer thickness (or the number of the layers) between the surfaces
      increases the shear stress at the onset of slip. In the vapor phase experiments,
      the stick-slip is enhanced by the increase of the negative Laplace pressure in
      the capillary condensed liquid, thereby forcing the surfaces toward each other
      more strongly with decreasing rvp. In the rvp range between 20% and 50%, where
      the fading stick-slip is observed, the condensate liquid seeps into the contact
      area under the influence of the applied tangential force and thus triggers the
      slip motion. Due to the small condensation volume, the liquid condensed around
      the contact area is exhausted in the process of repeating stick-slip. As the slip
      length is limited to the meniscus size, the stick-slip amplitude becomes smaller,
      and eventually the surfaces start sliding without stick-slip.

PMID- 17518484
TI  - Superhydrophobic polyolefin surfaces: controlled micro- and nanostructures.
AB  - Superhydrophobic polyolefin surfaces were prepared by simultaneous micro- and
      nanostructuring. Electropolished aluminum foil was microstructured with a micro
      working robot and then anodized in polyprotic acid. The surface microstructure
      can be tailored by adjusting the settings of the micro working robot and the
      nanostructure by adjusting the parameters of the anodization procedure. Surface
      structuring was done by injection molding where a microstructured anodized
      aluminum oxide mold insert was used to pattern the surfaces. Structuring had a
      marked effect on the contact angle between the injection-molded polyolefins and
      water. When the optimized microstructure was covered with nanostructure, the
      static contact angle between polypropylene and water obtained a value of about
      165 degrees and the sliding angle decreased to about 2.5 degrees. The
      superhydrophobic state was achieved.

PMID- 17518485
TI  - Silver-protein (core-shell) nanoparticle production using spent mushroom
      substrate.
AB  - A simple route for the synthesis of silver-protein (core-shell) nanoparticles
      using spent mushroom substrate (SMS) has been demonstrated in this work. SMS
      exhibits an organic surface that reduces silver ions and stabilizes the silver
      nanoparticles by a secreted protein. The silver nitrate solution incubated with
      SMS changed to a yellow color from 24 h onward, indicating the formation of
      silver nanoparticles. The purified solution yielded the maximum absorbance at 436
      nm due to surface plasmon resonance of the silver nanoparticles. X-ray analysis
      of the freeze-dried powder of silver nanoparticles confirmed the formation of
      metallic silver. Transmission electron microscopic analysis of the samples showed
      a uniform distribution of nanoparticles, having an average size of 30.5 +/- 4.0
      nm, and its corresponding electron diffraction pattern confirmed the face
      centered cubic (fcc) crystalline structure of metallic silver. The characteristic
      fluorescence of the protein shell at 435 nm was observed for the silver
      nanoparticles in solution, when excited at 280 nm, while Fourier transform
      infrared (FTIR) spectroscopy confirmed the presence of a protein shell. The
      silver nanoparticles were found to be stable in solution for more than 6 months.
      It is observed that the reducing agents from the safflower stalks caused the
      reduction of silver ions while protein secreted by the fungus stabilized the
      silver nanoparticles. These silver nanoparticles showed excellent antibacterial
      activity against two representative bacteria, Staphylococcus aureus (Gram
      positive) and Klebsiella pneumoniae (Gram negative), in spite of the presence of
      an organic layer as a shell. Apart from ecofriendliness and easy availability,
      "SMS" as a biomanufacturing unit will give us an added advantage in ease of
      handling when compared to other classes of microorganisms.

PMID- 17518486
TI  - Tunable stabilization of gold nanoparticles in aqueous solutions by
      mononucleotides.
AB  - Gold nanoparticles are one of the popular nanomaterials, widely used in biosensor
      applications as well as nanostructure construction. An essential attribute of
      these gold nanoparticles (Au-nps) is their stabilization against salt-induced
      aggregation. In this work, utilization of deoxyribonucleotides (dNTPs) as a
      tunable surface-stabilization agent for Au-nps was investigated. It was found
      that surfaces of Au-nps are covered by a layer of dNTPs after an adequate
      incubation with dNTPs solutions. Electrostatic repulsion among dNTP-coated Au-nps
      could prevent aggregation of Au-nps at a high salt concentration. The strength of
      dNTP-based protection can be manipulated by changing preparation protocols (e.g.,
      incubation temperature, ionic strength, and ratio of Au-nps to dNTPs). Four
      different types of dNTPs exhibit different binding affinity to Au-nps and thus
      various stabilization efficiency in the order of dATP > dCTP > dGTP approximately
      dTTP. Moreover, this salt-induced aggregation can be reinitiated by the increase
      of solution temperature, which leads to a partial removal of the protective dNTP
      layer on Au-nps. The advantage of thermally tunable aggregation/dispersion of Au
      nps mediated by dNTP adsorption offers a useful approach for the preparation of
      biomolecule (oligonucleotides and oligopeptides) modified nanoparticles in
      applications of bioassay and nanobiotechnology.

PMID- 17518488
TI  - Atomistic simulations of hydrated nafion and temperature effects on hydronium ion
      mobility.
AB  - The effects of hydration level and temperature on the nanostructure of an
      atomistic model of a Nafion (DuPont) membrane and the vehicular transport of
      hydronium ions and water molecules were examined using classical molecular
      dynamics simulations. Through the determination and analysis of structural and
      dynamical parameters such as density, radial distribution functions, coordination
      numbers, mean square deviations, and diffusion coefficients, we identify that
      hydronium ions play an important role in modifying the hydration structure near
      the sulfonate groups. In the regime of low level of hydration, short hydrogen
      bonded linkages made of water molecules and sometimes hydronium ions alone give a
      more constrained structure among the sulfonate side chains. The diffusion
      coefficient for water was found to be in good accord with experimental data. The
      diffusion coefficient for the hydronium ions was determined to be much smaller (6
      10 times) than that for water. Temperature was found to have a significant effect
      on the absolute value of the diffusion coefficients for both water and hydronium
      ions.

PMID- 17518487
TI  - Bladder cancer associated glycoprotein signatures revealed by urinary proteomic
      profiling.
AB  - Current methods in the noninvasive detection and surveillance of bladder cancer
      via urine analysis include voided urine cytology (VUC) and some diagnostic
      urinary protein biomarkers; however, due to the poor sensitivity of VUC and high
      false-positive rates of currently available protein assays, detection of bladder
      cancer via urinalysis remains a challenge. In the study presented here, a rapid,
      high-sensitivity technique was developed to profile the N-linked glycoprotein
      component in naturally micturated human urine specimens. Concanavalin A (Con A)
      affinity chromatography coupled to nanoflow liquid chromatography was utilized to
      separate the complex peptide mixture prior to a linear ion trap MS analysis. Of
      186 proteins identified with high confidence by multiple analyses, 40% were
      secreted proteins, 18% membrane proteins, and 14% extracellular proteins. In this
      study, the presence of several proteins appeared to be associated with the
      presence of bladder cancer, including alpha-1B-glycoprotein that was detected in
      all tumor-bearing patient samples but in none of the samples obtained from non
      tumor-bearing individuals. The combination of Con A affinity chromatography and
      nano-LC/MS/MS provides an initial investigation of N-glycoproteins in complex
      biological samples and facilitates the identification of potential biomarkers of
      bladder cancer in noninvasively obtained human urine.

PMID- 17518489
TI  - Comparison of electron injection dynamics from re-bipyridyl complexes to TiO2
      nanocrystalline thin films in different solvent environments.
AB  - Factors that control photoinduced interfacial electron transfer (ET) between
      molecular adsorbates and semiconductor nanoparticles have been intensely
      investigated in recent years. In this work, the solvent dependence of interfacial
      ET was studied by comparing ET rates in dye sensitized TiO2 nanocrystalline films
      in different solvent environments. Photoinduced ET rates from Re(LA)(CO)3Cl
      [LA=dcbpy=4,4'-dicarboxy-2,2'-bipyridine] (ReC1A) to TiO2 nanocrystalline thin
      films in air, pH buffer, MeOH, EtOH, and DMF were measured by femtosecond
      transient IR spectroscopy. The ET rates in these solvent environments were
      noticeably different. However, differences between the rates in pH buffer and
      nonaqueous solvents (MeOH, EtOH, and DMF) were much smaller than the values
      expected from much more negative TiO2 conduction band-edge positions in the
      latter solvents under anhydrous conditions. It was suggested that the presence of
      adsorbed water, which was evident in FTIR spectra, lowered the band edge of TiO2
      in these solvents and reduced the rate differences. The important effect of
      adsorbed water was verified by comparing two samples of Re(LP)(CO)3Cl [LP=2,2'
      bipyridine-4,4'-bis-CH2PO(OH)2] sensitized TiO2 in DMF, in which the presence of
      a trace amount of water was found to significantly increase the injection rate.

PMID- 17518490
TI  - Quantitative characterization of ion pairing and cluster formation in strong 1:1
      electrolytes.
AB  - Aqueous solutions of 1:1 strong electrolytes are considered to be the prototype
      for complete ionic dissociation. Nonetheless, clustering of strong 1:1
      electrolytes has been widely reported in all atom molecular dynamics simulations,
      and their presence is indirectly implicated in a diverse range of experimental
      results. Is there a physical basis for nonidealities such as ion pairing and
      cluster formation in aqueous solutions of strong 1:1 electrolytes? We attempt to
      answer this question by direct comparison of results from detailed molecular
      dynamics simulations to experimentally observed properties of 1:1 electrolytes.
      We report the analysis of a series of lengthy molecular dynamics simulations of
      alkali-halide solutions carried out over a wide range of physiologically relevant
      concentrations using explicit representations of water molecules. We find
      evidence for pronounced nonideal behavior of ions at all concentrations in the
      form of ion pairs and clusters which are in rapid equilibrium with dissociated
      ions. The phenomenology for ion pairing seen in these simulations is congruent
      with the multistep scheme proposed by Eigen and Tamm based on data from
      ultrasonic absorption experiments. For a given electrolyte, we show that the
      dependence of cluster populations on concentration can be described through a
      single set of equilibrium constants. We assess the accuracy of calculated ion
      pairing constants by favorable comparison to estimates obtained by Fuoss and co
      workers and based on conductometric experiments. Ion pairs and clusters form on
      length scales where the size of individual water molecules is as important as the
      hard core radius of ions. Ion pairing results as a balance between the favorable
      Coulomb interactions and the unfavorable partial desolvation of ions needed to
      form a pair.

PMID- 17518491
TI  - Proton hopping in phosphoric acid solvated nafion membrane: a molecular
      simulation study.
AB  - Molecular simulation studies of the microstructure and of the proton transport
      properties of phosphoric acid solvated Nafion membrane are carried out. The ab
      initio calculations show that the phosphoric acid is a good solvent to promote
      the proton ionization of the sulfonic acid group, and only two phosphoric acid
      molecules are necessary for the dissociation of one sulfonic acid group. A
      mechanism of proton hopping between phosphoric acid and protonated phosphoric
      acid cation in the hydrophilic subphase is also elucidated by ab initio
      calculations. The molecular dynamics simulations, conducted at a phosphoric acid
      concentration of 25.4% (wt) which is slightly lower than that of phosphoric acid
      swollen Nafion, show that the phosphoric acid exists in subphases and that it
      cannot develop into a continuous subphase. Thus, proton-hopping pathways are
      interrupted, and the conductivity is expected to be lower than that for pure
      phosphoric acid. The molecular dynamics simulations, conducted at a phosphoric
      acid concentration of 45.1% (wt) which corresponds to an unstable state, show
      that the hydrophobic poly(tetrafluoroethylene) backbones trend to gather together
      forming hydrophobic clusters and that the phosphoric acid forms a continuous
      subphase with the sulfonic acid groups located at the hydrophobic/hydrophilic
      interface. Thus, proton-hopping pathways can develop uninterruptedly like the
      pure phosphoric acid, and high conductivity is expected. The molecular dynamics
      study also shows that the hydrogen-bonding characteristics of phosphoric acid and
      sulfonate anion are similar regardless of the factor that the former can move
      freely while the latter is attached to Nafion backbone.

PMID- 17518492
TI  - Effect of water and organic solvents on the ionic dissociation of ionic liquids.
AB  - The effect of water and several organic solvents on the density, viscosity, and
      conductivity of ionic liquids (ILs) 1-n-butyl-3-methylimidazolium
      hexafluorophosphate ([bmim][PF6]), 1-n-butyl-3-methylimidazolium
      tetrafluoroborate ([bmim][BF4]), and 1-n-butyl-3-methylimidazolium
      trifluoroacetate ([bmim][CF3CO2]) was studied at 298.15 K in wide composition
      ranges. The density, viscosity, and conductivity of the three neat ILs were also
      determined at various temperatures. Upon the basis of the molar conductivity of
      the mixtures and that of the neat ILs of the same viscosity, the degree of
      dissociation of ILs in the solutions was investigated. It can be deduced that the
      organic solvents enhance the ionic association of the ILs, the effect depending
      on the solvent dielectric constant, while water promotes dissociation
      significantly due to its high dielectric constant and its ability to form strong
      hydrogen bonds with the anions of the ILs.

PMID- 17518493
TI  - Control of the fixed charge distribution in an ion-exchange membrane via
      diffusion and the reaction rate of the monomer.
AB  - The fixed charge distribution of the ion-exchange membranes was controlled by
      introducing ion-exchangeable groups onto the glycidyl methacrylate (GMA)-g
      polypropylene (PP) membranes. The membranes were prepared by plasma-induced graft
      polymerization with uniform or nonuniform graft distributions over the cross
      section. The effects of reaction conditions on the graft distribution in plasma
      induced graft polymerization were investigated to obtain the GMA-g-PP membranes
      with different graft distributions. The examined reaction conditions were plasma
      power, gas pressure of the plasma, solvent, concentration of the monomer
      solution, and reaction temperature. The graft distribution of the membranes was
      directly observed by a microscopic Fourier transform infrared mapping method and
      field-emission scanning electron microscopy. Also, the graft distribution was
      correlated with the relative magnitude of the reaction rate to the diffusion
      rate, which may determine the grafting yield as a function of the distance from
      the surface. A high rate of diffusion compared to the reaction rate resulted in a
      more uniform graft distribution. Among the grafting conditions, control of the
      reaction temperature was found to be the most effective for selectively preparing
      both uniform and nonuniform graft distribution. Uniform graft distribution was
      achieved when the reaction was conducted at 1 degrees C because of the relatively
      rapid diffusion and the slow reaction of the monomer, while nonuniform graft
      distribution occurred at higher reaction temperatures. Consequently, uniformly
      and nonuniformly charged cation-exchange membranes were prepared through
      sulfonation of the corresponding GMA-g-PP membranes at temperatures of 1 and 40
      degrees C, respectively.

PMID- 17518494
TI  - Experimental and computational study of the thermochemistry of the
      fluoromethylaniline isomers.
AB  - The standard (po = 0.1 MPa) molar enthalpies of formation in the condensed phase
      of seven isomers of fluoromethylaniline were derived from the standard molar
      energies of combustion, in oxygen, to yield CO2(g), N2(g) and HF.10H2O(l), at T =
      298.15 K, measured by rotating bomb combustion calorimetry. The standard molar
      enthalpies of vaporization or sublimation of these compounds, also at T = 298.15
      K, were determined using Calvet microcalorimetry, while the enthalpies of fusion
      of the solid compounds were determined by differential scanning calorimetry. The
      standard molar enthalpies of formation in the gaseous phase, at T = 298.15 K,
      were derived from the former two experimental quantities. G3MP2//B3LYP
      calculations were performed for all possible fluoromethylanilines allowing the
      estimation of data for the isomers that were not studied experimentally. The Cox
      scheme was applied with two different approaches for the estimation of the
      standard molar enthalpies of formation of all the isomers studied, and this led
      to the conclusion that the literature values for the enthalpies of formation of
      the meta and para isomers of methylaniline seem to be not reliable. Further
      G3MP2//B3LYPs calculations on the methylaniline isomers yielded new values for
      the standard molar enthalpies of formation of the isomers of methylaniline, which
      have been tested under the Cox scheme, resulting in better estimates.

PMID- 17518495
TI  - Structure control for fine tuning fluorescence emission from side-chain
      azobenzene polymers.
AB  - New fluorescent azobenzene dyes and side-chain polymers have been synthesized and
      characterized and their photophysical properties studied. A series of azobenzene
      dyes having different fluorophores such as phenol (S1), phenylphenol (S2) and
      naphthol (S3) incorporated in them were synthesized. S2 had unusually high
      fluorescence with a quantum yield of phi f = 0.2 recorded in dichloromethane
      (DCM), whereas S1 and S3 were found to be weakly fluorescent. The azobenzene dyes
      were converted into methacrylate monomers having short ethyleneoxy spacers and
      then free radically polymerized. Phenylphenol-based azobenzene polymer (P2)
      continued to show fluorescence, whereas fluorescence was completely quenched in
      the case of phenol (P1)- and naphthol (P3)-based polymers. Phenylphenol, though
      twisted in the ground state is known to have a more planar geometry in the
      excited state--a factor that enables it to retain its fluorescence behavior even
      when it is incorporated as part of an azobenzene unit. In contrast, naphthol,
      which is a better fluorophore compared to phenylphenol, loses much of its
      emissive behavior upon coupling to the azobenzene unit. The extent of trans to
      cis photoisomerization in solution was very low (approximately 17%) for P2 after
      30 min of continuous irradiation using 365 nm light, in contrast to approximately
      40% for P1 under identical conditions. This is attributed to the steric repulsion
      brought about by the bulky phenylphenol units that restrict rotation. A 2-fold
      enhancement in fluorescence emission was observed for P2 upon irradiation by UV
      light at 360 nm, which relaxed to the original intensity in about 7 day's time.
      The higher emission of the cis azobenzenes is generally attributed to an
      inhibition of photoinduced electron transfer (PET) mechanism. The emission of P2
      showed a concentration dependence which increased initially and then decreased in
      intensity with the formation of a new red-shifted peak at higher concentration
      due to aggregation. Irradiation of the fluorescence quenched highly concentrated
      (1 x 10(-3) M) sample of P2 showed an enhancement in emission from aggregates at
      532 nm.

PMID- 17518496
TI  - ESEEM studies of peptide nitrogen hyperfine coupling in tyrosyl radicals and
      model peptides.
AB  - Tyrosyl radicals are important in long-range electron transfer in several
      enzymes, but the protein environmental factors that control midpoint potential
      and electron transfer rate are not well understood. To develop a more detailed
      understanding of the effect of protein sequence, we have performed 14N and 15N
      electron spin echo envelope modulation (ESEEM) measurements on tyrosyl radical,
      generated either in polycrystalline tyrosinate or in its 15N-labeled isotopomer,
      by UV photolysis. 14N-ESEEM was also performed on tyrosyl radical generated in
      tyrosine-containing pentapeptide samples. Simulation of the 14N- and 15N-tyrosyl
      radical ESEEM measurements yielded no significant isotropic hyperfine splitting
      to the amine or amide nitrogen; the amplitude of the anisotropic, nitrogen
      hyperfine coupling (0.21 MHz) was consistent with a dipole-dipole distance of 3.0
      A. Density functional theory was used to calculate the isotropic and anisotropic
      hyperfine couplings to the amino nitrogen in four different tyrosyl radical
      conformers. Comparison with the simulated data suggested that the lowest energy
      radical conformer, generated in tyrosine at pH 11, has a 76 degrees Calpha-Cbeta
      C1'-C2' ring and a -73 degrees C-Calpha-Cbeta-C1' backbone dihedral angle. In
      addition, the magnitude, orientation, and asymmetry of the nuclear quadrupole
      coupling tensor were derived from analysis of the tyrosyl radical 14N-ESEEM. The
      simulations showed differences in the coupling and orientation of the nuclear
      quadrupole tensor, when the tyrosinate and pentapeptide samples were compared.
      These results suggest sequence- or conformation-induced changes in the ionic
      character of the NH bond in different tyrosine-containing peptides.

PMID- 17518497
TI  - Normal vibrational analysis of a trans-planar syndiotactic polystyrene chain.
AB  - The full vibrational spectra of alpha and beta crystalline phases of syndiotactic
      polystyrene (sPS), that is, phases presenting the trans-planar conformation, have
      been experimentally determined and compared with that calculated at the B3LYP/6
      31G(d,p) level of theory for an infinite trans-planar chain. The normal
      vibrational analysis of most representative modes of the periodic model allowed
      us to give a general description of each one, which was further confirmed by the
      direct inspection of mode animations. An assignment of the different modes was
      performed in terms of frequency, relative intensity, and direction of the
      transition-moment vector of the observed IR peaks as well as Raman vibrational
      frequencies.

PMID- 17518498
TI  - Direct synthesis of magnesium porphine via 1-formyldipyrromethane.
AB  - The reaction of 1-formyldipyrromethane (100 mM) in toluene at 115 degrees C
      containing DBU (10 mol equiv) and MgBr2 (3 mol equiv) in the presence of air
      affords the magnesium chelate Mg(II) porphine in 30-40% yield. The advantages of
      the new method include simplicity, high concentration, chromatography-free
      purification, gram-scale synthesis, and avoidance of the poorly soluble free base
      porphine. Mg(II) porphine exhibits good solubility in common organic solvents and
      is a valuable core scaffold for derivatization.

PMID- 17518499
TI  - Enantioselective total synthesis of phomallenic acid C.
AB  - The newly isolated bacterial FAS II inhibitor phomallenic acid C (3) was
      synthesized for the first time as a 16:1 mixture of the (R)- and (S)-isomer with
      the diyne-allene motif constructed using a coupling under Negishi conditions. By
      comparison with the synthetic sample, the natural phomallenic acid C was
      estimated to be a 3.8:1 mixture of (R)-/(S)-isomers. This synthesis describes a
      new synthetic entry to optically active allene diynes.

PMID- 17518500
TI  - Synthesis of C13-C25 fragment of 24-demethylbafilomycin C(1) via
      diastereoselective aldol reactions of a ketone boron enolate as the key step.
AB  - An efficient synthesis of the C13-C25 fragment is described for 24
      demethylbafilomycin C1, a new member of the plecomacrolide family isolated from
      fermentation broth of Streptomyces sp. CS which is a commensal microbe of
      Maytenus hookeri. The targeted C13-C25 fragment possesses five oxygenated and
      three methyl-substituted stereogenic centers. It is obtained through formation of
      the C17-C18 syn aldol by using an ethyl ketone boron enolate with diastereomeric
      ratios of 95:5 and 83:17, respectively, for the chiral aldehydes substituted with
      acetoxy and methoxyacetoxy groups at C15. The results confirm the observation
      that the stereochemistry at C22 of the ketone is determinant to the
      diastereoselectivity of the aldol reaction. The synthesized C13-C25 fragment
      having a methoxyacetoxy group at C15 is considered as a useful precursor for
      construction of the 16-membered ring lactone of 24-demethylbafilomycin C1 through
      an aldol condensation of the methoxyacetate followed by formation of the C12-C13
      double bond via a diene-ene RCM reaction.

PMID- 17518502
TI  - Catalysis in ionic liquids.

PMID- 17518501
TI  - Green chemistry considerations in entropic control of materials and processes.

PMID- 17518503
TI  - Lanthanides and actinides in ionic liquids.

PMID- 17518504
TI  - Organic nanowire-templated fabrication of alumina nanotubes by atomic layer
      deposition.
AB  - Alumina nanotubes were fabricated by a template method. Tris-(8-hydroxyquinoline)
      gallium (GaQ3) organic nanowires were used as a soft template for coating with
      alumina using an atomic layer deposition technique. The deposition was conducted
      at 25 degrees C by using trimethylaluminum and distilled water as the precursors
      of Al2O3. Amorphous alumina nanotubes were obtained after removing the GaQ3 by
      dissolving in toluene or by heat treatment at 350 degrees C. The amorphous
      nanotubes could be crystallized by heating at 900 degrees C for 1 h in vacuum.

PMID- 17518505
TI  - Molecular-scale soft imprint lithography for alignment layers in liquid crystal
      devices.
AB  - We describe molecular-scale soft nanoimprint lithographic replication of rubbed
      polyimide substrates to form alignment layers for liquid crystal devices.
      Systematic studies of the surface relief morphology of the polyimide and molded
      structures in three different polymers illustrate good lithographic fidelity down
      to relief heights of several nanometers, and with some capabilities at the level
      of approximately 1 nm. Collective results of experiments with several polymer
      formulations for molds and molded materials and process conditions indicate that
      this molecular-scale fidelity in replication can be used to produce surfaces that
      will effectively align liquid crystal molecules. Good electro-optical responses
      from liquid crystal light modulators that are formed in this manner suggest
      utility for fundamental studies and potential practical application.

PMID- 17518508
TI  - Pharmacokinetics of cinacalcet hydrochloride when administered with ketoconazole.
AB  - BACKGROUND AND OBJECTIVE: The calcimimetic cinacalcet hydrochloride (cinacalcet)
      is used for treatment of patients with chronic kidney disease with secondary
      hyperparathyroidism, a population that commonly receives multiple concurrent
      medications. Cinacalcet is eliminated primarily via oxidative metabolism
      mediated, in part, through cytochrome P450 (CYP) 3A4. Thus, the potential for an
      inhibitor of CYP3A4 to alter the pharmacokinetics of cinacalcet is of clinical
      importance. The objective of this study was to evaluate the pharmacokinetics of
      cinacalcet during treatment with a potent CYP3A4 inhibitor, ketoconazole.
      SUBJECTS AND METHODS: Twenty-four healthy subjects were enrolled in an open
      label, crossover, phase I study to receive a single oral dose of cinacalcet (90
      mg) alone and with 7 days of ketoconazole (200mg twice daily). Blood samples for
      pharmacokinetics were collected for up to 72 hours postdose. Cinacalcet plasma
      concentration-time data were analysed by noncompartmental methods.
      Pharmacokinetic parameters were analysed using a crossover ANOVA model that
      included subjects who completed both treatment arms. RESULTS: Twenty subjects
      completed both treatment arms. The mean area under the plasma concentration-time
      curve of cinacalcet increased 2.3-fold (90% CI 1.92, 2.67) [range 1.15- to 7.12
      fold] and the mean maximum plasma concentration increased 2.2-fold (90% CI 1.67,
      2.78) [range 0.904- to 10.8-fold] when administered with ketoconazole, relative
      to when administered alone. The time to reach the maximum plasma concentration
      was not significantly affected, and the terminal elimination half-lives were
      similar between treatments. CONCLUSIONS: Co-administration of a potent CYP3A4
      inhibitor moderately increased cinacalcet exposure in study subjects. This
      suggests that clinicians should monitor parathyroid hormone and calcium
      concentrations when a patient receiving cinacalcet initiates or discontinues
      therapy with a strong CYP3A4 inhibitor.

PMID- 17518506
TI  - Expression of adenosine triphosphate-binding cassette (ABC) drug transporters in
      peripheral blood cells: relevance for physiology and pharmacotherapy.
AB  - Adenosine triphosphate-binding cassette (ABC)-type transport proteins were
      initially described for their ability to reduce intracellular concentrations of
      anticancer compounds, thereby conferring drug resistance. In recent years,
      expression of this type of proteins has also been reported in numerous cell types
      under physiological conditions; here, these transporters are often reported to
      alter systemic and local drug disposition (e.g. in the brain or the
      gastrointestinal tract). In this context, peripheral blood cells have also been
      found to express several ABC-type transporters. While erythrocytes mainly express
      multidrug resistance protein (MRP) 1, MRP4 and MRP5, which are discussed with
      regard to their involvement in glutathione homeostasis (MRP1) and in the efflux
      of cyclic nucleotides (MRP4 and MRP5), leukocytes also express P-glycoprotein and
      breast cancer resistance protein. In the latter cell types, the main function of
      efflux transporters may be protection against toxins, as these cells demonstrate
      a very high turnover rate. In platelets, only two ABC transporters have been
      described so far. Besides MRP1, platelets express relatively high amounts of MRP4
      not only in the plasma membrane but also in the membrane of dense granules,
      suggesting relevance for mediator storage. In addition to its physiological
      function, ABC transporter expression in these structures can be of
      pharmacological relevance since all systemic drugs reach their targets via
      circulation, thereby enabling interaction of the therapeutic agent with
      peripheral blood cells. Moreover, both intended effects and unwanted side effects
      occur in peripheral blood cells, and intracellular micropharmacokinetics can be
      affected by these transport proteins. The present review summarises the data
      available on expression of ABC transport proteins in peripheral blood cells.

PMID- 17518507
TI  - A systematic review of limited sampling strategies for platinum agents used in
      cancer chemotherapy.
AB  - Despite evidence in the literature suggesting that a strong correlation exists
      between the pharmacokinetic parameters and pharmacodynamic effect of anticancer
      agents, many of these agents are still dosed by body surface area. Therapeutic
      drug monitoring with the aim of pharmacokinetic-guided dosing would not only
      maintain target concentrations associated with efficacy but may potentially
      minimise the likelihood of dose-related systemic toxicities. The pharmacokinetic
      parameter that displays the best correlation with the pharmacodynamics of
      anticancer drugs is the area under the plasma concentration-time curve (AUC).
      However, accurate determination of the AUC requires numerous blood samples over
      an extended interval, which is not feasible in clinical practice. Therefore,
      limited sampling strategies (LSSs) have been proposed as a means to accurately
      and precisely estimate pharmacokinetic parameters with a minimal number of blood
      samples. LSSs have been developed for many drugs, particularly ciclosporin and
      other immunosuppressants, as well as for certain anticancer drugs. This
      systematic review evaluates LSSs developed for the platinum compounds and
      categorises 18 pertinent citations according to criteria adapted from the US
      Preventive Services Task Force. Thirteen citations (four level I, six level II-1,
      three level II-2) pertained to LSSs for carboplatin, four citations (one level II
      1, one level II-2, two level III) to cisplatin LSSs, and one citation (level II
      2) to nedaplatin. Based on the current evidence, it appears that LSSs may be
      useful for pharmacokinetic-guided dosage adjustments of carboplatin in both
      adults and children with cancer. Although some validation studies suggest that
      LSSs can be extended to different cancer populations or different chemotherapy
      regimens, other studies dispute this finding. Although the use of LSSs to predict
      the pharmacokinetic parameters of cisplatin and nedaplatin appear promising, the
      quality of evidence from published studies does not support routine
      implementation at this time.LSSs represent one approach in which clinicians can
      make specific dosage adjustments for individual patients to optimise outcomes.
      However, the limitations of these strategies must also be taken into
      consideration. There is also a need for prospective studies to demonstrate that
      application of LSSs for platinum agents ultimately improves patient response and
      decreases systemic toxicities.

PMID- 17518509
TI  - Population pharmacokinetics of levetiracetam in Japanese and Western adults.
AB  - OBJECTIVE: To assess the population pharmacokinetics of levetiracetam, a second
      generation antiepileptic drug, in adult Japanese and Western populations.
      METHODS: Data were pooled from ten matched clinical trials conducted in Japan and
      in Europe and the USA, in which levetiracetam was administered orally to healthy
      subjects and subjects with epilepsy. Overall, 5408 plasma concentrations were
      available from 524 subjects in six clinical pharmacology studies and two
      confirmatory and two long-term safety studies of add-on treatment for partial
      epilepsy. A one-compartment open model with first-order absorption and
      elimination was fitted to the plasma concentrations using nonlinear mixed-effects
      modelling with first-order estimation. RESULTS: Ethnicity had no statistically
      significant effect on the pharmacokinetics of levetiracetam in the presence of
      the other covariates. Bodyweight, sex, creatinine clearance and concomitant
      intake of enzyme inducers or valproic acid had a statistically significant effect
      on apparent plasma clearance of levetiracetam. Bodyweight, disease and valproic
      acid had a statistically significant effect on the volume of distribution.
      Levetiracetam exposure (the area under the plasma concentration-time curve over
      the 12-hour dosing interval at steady state) was 12% higher in females than in
      males. Decreasing bodyweight from 70 kg to 40 kg was predicted to increase
      exposure by 16%, while halving creatinine clearance was predicted to increase
      exposure by 10%. Enzyme inducers reduced exposure by 8%, while valproic acid
      resulted in a 23% increase in exposure. The latter effect was assumed to arise
      from the known association between valproic acid and increased body fat, since
      levetiracetam is negligibly metabolised by cytochrome P450 enzymes. CONCLUSIONS:
      Population pharmacokinetic analysis points to the absence of ethnic differences
      in the pharmacokinetics of levetiracetam between Japanese and Western
      populations, other than those arising from bodyweight differences. Small,
      clinically non-relevant differences between individual demographic
      characteristics suggest that dose adjustment is usually not necessary.

PMID- 17518510
TI  - Pharmacokinetics of taurolidine following repeated intravenous infusions measured
      by HPLC-ESI-MS/MS of the derivatives taurultame and taurinamide in glioblastoma
      patients.
AB  - BACKGROUND AND OBJECTIVE: Taurolidine is known to have antimicrobial activity.
      Furthermore, at lower concentrations, it has been found to exert a selective
      antineoplastic effect in vitro and in vivo. The aim of this study was to
      investigate the pharmacokinetics of taurolidine in vivo following repeated
      intravenous infusion in a schedule used for the treatment of glioblastoma. As a
      prerequisite, the pharmacokinetics of taurolidine in human blood plasma and whole
      blood in vitro was investigated. PATIENTS AND METHODS: The pharmacokinetics of
      taurolidine and its derivatives taurultame and taurinamide were investigated in
      human blood plasma and in whole blood in vitro using blood from a healthy male
      volunteer. During repeated intravenous infusion therapy with taurolidine, plasma
      samples were taken every hour for a period of 13 hours per day in seven patients
      (three male, four female; mean age 48.4 +/- 12.8 years, range 27-66 years) with a
      glioblastoma. Following dansyl derivatisation, the concentrations of taurultame
      and taurinamide were determined using a new method based on high-performance
      liquid chromatography (HPLC) online coupled to electrospray ionisation tandem
      mass spectrometry (ESI-MS/MS) in the multiple reaction monitoring mode. Under the
      experimental conditions used, taurolidine could not be determined directly and
      was back-calculated from the taurultame and taurinamide values. RESULTS: The new
      HPLC-ESI-MS/MS method demonstrated high accuracy and reproducibility. In vitro
      plasma concentrations of taurultame and taurinamide remained constant over the
      incubation period. In whole blood in vitro, a time-dependent formation of
      taurinamide was observed. At the start of the incubation, the taurultame
      taurinamide ratio (TTR) was 0.95 at an initial taurolidine concentration of 50
      microg/mL, and 1.69 at 100 microg/mL. The concentration of taurultame decreased
      at the same rate as the taurinamide concentration increased, showing logarithmic
      kinetics. The calculated taurolidine concentration remained largely constant over
      the 6-hour incubation period. During repeated infusions in patients, calculated
      plasma concentrations of taurolidine showed a strong increase after the start of
      each infusion and continued to increase until the end of infusion, followed by a
      rapid decline. The TTR was found to fluctuate between 0.1 and 0.3, depending on
      the relation to the previous or next infusion period. The volume of distribution
      was markedly higher for taurolidine, taurultame and taurinamide than the plasma
      volume. CONCLUSIONS: Taurolidine displayed a stable pattern of derivatives in
      plasma in vitro, whereas in whole blood, a time- and concentration-dependent
      conversion was apparent. In patients, the calculated average taurolidine plasma
      concentration, achieved with the repeated infusion regimen, was in the
      antineoplastic-effective concentration range. The tissue concentrations of
      taurolidine and taurultame are expected to be higher than the plasma
      concentrations, taking into account the calculated volumes of distribution.
      Repeated infusion of taurolidine is the therapeutically adequate mode of
      administration for the indication of glioblastoma.

PMID- 17518511
TI  - Pharmacokinetics and safety of ebastine in healthy subjects and patients with
      renal impairment.
AB  - OBJECTIVE: To assess the differences in the pharmacokinetics and cardiac safety
      of ebastine and its active metabolite, carebastine, in patients with normal and
      impaired renal function. METHODS: Twenty-four patients with varying degrees of
      renal impairment (mild, moderate or severe: n = 8 per group) and 12 healthy
      subjects participated in an open-label, parallel-group, multicentre study.
      Ebastine 20mg was administered orally once daily for 5 days. Plasma
      concentrations of ebastine and carebastine were determined for 24 hours on day 1
      and for 72 hours on day 5 by using a validated sensitive liquid chromatography
      tandem mass spectrometry assay with a minimum quantifiable limit of 0.05 ng/mL
      for ebastine and 1.00 ng/mL for carebastine. Renal function was assessed by
      measuring 24-hour creatinine clearance (CL(CR)) at baseline. Cardiac and general
      safety parameters were also monitored. RESULTS: The pharmacokinetics of ebastine
      were not modified by renal impairment. No correlation between ebastine
      pharmacokinetics and renal function, as expressed by CL(CR) assessed 2 days prior
      to dosing, was observed. Comparison of the plasma exposure and the elimination
      half-life of ebastine and carebastine between groups showed no significant
      differences. Therefore, no apparent accumulation of ebastine and carebastine
      occurred, and steady-state concentrations of ebastine and carebastine were
      predictable from single-dose pharmacokinetics for both healthy subjects and
      patients with renal impairment, even though the variability between the groups
      was large. In addition, no differences were observed in the safety of ebastine
      between patients with renal impairment and healthy subjects when assessing
      adverse events, vital signs, laboratory parameters or ECGs. CONCLUSION: Ebastine
      was generally well tolerated in subjects with impaired renal function. No
      clinically important pharmacokinetic or safety differences were observed between
      patients with renal impairment and healthy subjects with normal renal function.

PMID- 17518512
TI  - Using Clinical Evidence in a national continuing medical education program in
      Italy.

PMID- 17518513
TI  - Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone
      therapy: a drug-drug interaction?
AB  - BACKGROUND: Suppression of prostacyclin (PGI2) is implicated in the
      cardiovascular hazard from inhibitors of cyclooxygenase (COX)-2. Furthermore,
      estrogen confers atheroprotection via COX-2-dependent PGI2 in mice, raising the
      possibility that COX inhibitors may undermine the cardioprotection, suggested by
      observational studies, of endogenous or exogenous estrogens. METHODS AND
      FINDINGS: To identify an interaction between hormone therapy (HT) and COX
      inhibition, we measured a priori the association between concomitant nonsteroidal
      anti-inflammatory drugs (NSAIDs), excluding aspirin, in peri- and postmenopausal
      women on HT and the incidence of myocardial infarction (MI) in a population-based
      epidemiological study. The odds ratio (OR) of MI in 1,673 individuals and 7,005
      controls was increased from 0.66 (95% confidence interval [CI] 0.50-0.88) when
      taking HT in the absence of traditional (t)NSAIDs to 1.50 (95% CI 0.85-2.64) when
      taking the combination of HT and tNSAIDs, resulting in a significant (p < 0.002)
      interaction. The OR when taking aspirin at doses of 150 mg/d or more was 1.41
      (95% CI 0.47-4.22). However, a similar interaction was not observed with other
      commonly used drugs, including lower doses of aspirin, which target
      preferentially COX-1. CONCLUSIONS: Whether estrogens confer cardioprotection
      remains controversial. Such a benefit was observed only in perimenopausal women
      in the only large randomized trial designed to address this issue. Should such a
      benefit exist, these results raise the possibility that COX inhibitors may
      undermine the cardioprotective effects of HT.

PMID- 17518514
TI  - Hyperoxic brain effects are normalized by addition of CO2.
AB  - BACKGROUND: Hyperoxic ventilation (>21% O2) is widely used in medical practice
      for resuscitation, stroke intervention, and chronic supplementation. However,
      despite the objective of improving tissue oxygen delivery, hyperoxic ventilation
      can accentuate ischemia and impair that outcome. Hyperoxia results in,
      paradoxically, increased ventilation, which leads to hypocapnia, diminishing
      cerebral blood flow and hindering oxygen delivery. Hyperoxic delivery induces
      other systemic changes, including increased plasma insulin and glucagon levels
      and reduced myocardial contractility and relaxation, which may derive partially
      from neurally mediated hormonal and sympathetic outflow. Several cortical,
      limbic, and cerebellar brain areas regulate these autonomic processes. The aim of
      this study was to assess recruitment of these regions in response to hyperoxia
      and to determine whether any response would be countered by addition of CO2 to
      the hyperoxic gas mixture. METHODS AND FINDINGS: We studied 14 children (mean age
      11 y, range 8-15 y). We found, using functional magnetic resonance imaging, that
      2 min of hyperoxic ventilation (100% O2) following a room air baseline elicited
      pronounced responses in autonomic and hormonal control areas, including the
      hypothalamus, insula, and hippocampus, throughout the challenge. The addition of
      5% CO2 to 95% O2 abolished responses in the hypothalamus and lingual gyrus,
      substantially reduced insular, hippocampal, thalamic, and cerebellar patterns in
      the first 48 s, and abolished signals in those sites thereafter. Only the dorsal
      midbrain responded to hypercapnia, but not hyperoxia. CONCLUSIONS: In this group
      of children, hyperoxic ventilation led to responses in brain areas that modify
      hypothalamus-mediated sympathetic and hormonal outflow; these responses were
      diminished by addition of CO2 to the gas mixture. This study in healthy children
      suggests that supplementing hyperoxic administration with CO2 may mitigate
      central and peripheral consequences of hyperoxia.

PMID- 17518515
TI  - Vaccinating to protect a vulnerable subpopulation.
AB  - BACKGROUND: Epidemic influenza causes serious mortality and morbidity in
      temperate countries each winter. Research suggests that schoolchildren are
      critical in the spread of influenza virus, while the elderly and the very young
      are most vulnerable to the disease. Under these conditions, it is unclear how
      best to focus prevention efforts in order to protect the population. Here we
      investigate the question of how to protect a population against a disease when
      one group is particularly effective at spreading disease and another group is
      more vulnerable to the effects of the disease. METHODS AND FINDINGS: We developed
      a simple mathematical model of an epidemic that includes assortative mixing
      between groups of hosts. We evaluate the impact of different vaccine allocation
      strategies across a wide range of parameter values. With this model we
      demonstrate that the optimal vaccination strategy is extremely sensitive to the
      assortativity of population mixing, as well as to the reproductive number of the
      disease in each group. Small differences in parameter values can change the best
      vaccination strategy from one focused on the most vulnerable individuals to one
      focused on the most transmissive individuals. CONCLUSIONS: Given the limited
      amount of information about relevant parameters, we suggest that changes in
      vaccination strategy, while potentially promising, should be approached with
      caution. In particular, we find that, while switching vaccine to more active
      groups may protect vulnerable groups in many cases, switching too much vaccine,
      or switching vaccine under slightly different conditions, may lead to large
      increases in disease in the vulnerable group. This outcome is more likely when
      vaccine limitation is stringent, when mixing is highly structured, or when
      transmission levels are high.

PMID- 17518516
TI  - Understanding the slow depletion of memory CD4+ T cells in HIV infection.
AB  - BACKGROUND: The asymptomatic phase of HIV infection is characterised by a slow
      decline of peripheral blood CD4(+) T cells. Why this decline is slow is not
      understood. One potential explanation is that the low average rate of homeostatic
      proliferation or immune activation dictates the pace of a "runaway" decline of
      memory CD4(+) T cells, in which activation drives infection, higher viral loads,
      more recruitment of cells into an activated state, and further infection events.
      We explore this hypothesis using mathematical models. METHODS AND FINDINGS: Using
      simple mathematical models of the dynamics of T cell homeostasis and
      proliferation, we find that this mechanism fails to explain the time scale of
      CD4(+) memory T cell loss. Instead it predicts the rapid attainment of a stable
      set point, so other mechanisms must be invoked to explain the slow decline in
      CD4(+) cells. CONCLUSIONS: A runaway cycle in which elevated CD4(+) T cell
      activation and proliferation drive HIV production and vice versa cannot explain
      the pace of depletion during chronic HIV infection. We summarize some alternative
      mechanisms by which the CD4(+) memory T cell homeostatic set point might slowly
      diminish. While none are mutually exclusive, the phenomenon of viral rebound, in
      which interruption of antiretroviral therapy causes a rapid return to
      pretreatment viral load and T cell counts, supports the model of virus adaptation
      as a major force driving depletion.

PMID- 17518517
TI  - Time scales of CD4+ T cell depletion in HIV infection.

PMID- 17518518
TI  - Structural analysis of CsoS1A and the protein shell of the Halothiobacillus
      neapolitanus carboxysome.
AB  - The carboxysome is a bacterial organelle that functions to enhance the efficiency
      of CO2 fixation by encapsulating the enzymes ribulose bisphosphate
      carboxylase/oxygenase (RuBisCO) and carbonic anhydrase. The outer shell of the
      carboxysome is reminiscent of a viral capsid, being constructed from many copies
      of a few small proteins. Here we describe the structure of the shell protein
      CsoS1A from the chemoautotrophic bacterium Halothiobacillus neapolitanus. The
      CsoS1A protein forms hexameric units that pack tightly together to form a
      molecular layer, which is perforated by narrow pores. Sulfate ions, soaked into
      crystals of CsoS1A, are observed in the pores of the molecular layer, supporting
      the idea that the pores could be the conduit for negatively charged metabolites
      such as bicarbonate, which must cross the shell. The problem of diffusion across
      a semiporous protein shell is discussed, with the conclusion that the shell is
      sufficiently porous to allow adequate transport of small molecules. The molecular
      layer formed by CsoS1A is similar to the recently observed layers formed by
      cyanobacterial carboxysome shell proteins. This similarity supports the argument
      that the layers observed represent the natural structure of the facets of the
      carboxysome shell. Insights into carboxysome function are provided by comparisons
      of the carboxysome shell to viral capsids, and a comparison of its pores to the
      pores of transmembrane protein channels.

PMID- 17518519
TI  - The mother centriole plays an instructive role in defining cell geometry.
AB  - Centriole positioning is a key step in establishment and propagation of cell
      geometry, but the mechanism of this positioning is unknown. The ability of pre
      existing centrioles to induce formation of new centrioles at a defined angle
      relative to themselves suggests they may have the capacity to transmit spatial
      information to their daughters. Using three-dimensional computer-aided analysis
      of cell morphology in Chlamydomonas, we identify six genes required for centriole
      positioning relative to overall cell polarity, four of which have known
      sequences. We show that the distal portion of the centriole is critical for
      positioning, and that the centriole positions the nucleus rather than vice versa.
      We obtain evidence that the daughter centriole is unable to respond to normal
      positioning cues and relies on the mother for positional information. Our results
      represent a clear example of "cytotaxis" as defined by Sonneborn, and suggest
      that centrioles can play a key function in propagation of cellular geometry from
      one generation to the next. The genes documented here that are required for
      proper centriole positioning may represent a new class of ciliary disease genes,
      defects in which would be expected to cause disorganized ciliary position and
      impaired function.

PMID- 17518520
TI  - A field survey of iodine supplementation of primary school children and their
      parents in a rural village in the endemic area of iodine deficiency disorder,
      northeastern Thailand.
AB  - Iodine deficiency disorder (IDD) is an important health problem in Thailand. Due
      to the geographical limitation of marine salt distribution, the Northern and
      Northeastern regions of Thailand are endemic areas of this disorder. In this
      study, a cross-sectional survey on the domestic use of iodine-enriched salt by
      the people in a rural village, Non Sam Ran, Borabue district, Mahasarakarm
      province in the northeastern region of Thailand was conducted. A salt survey was
      undertaken in the village, involving the specific health knowledge of both
      primary school students and their parents, and including a home visit with
      kitchen salt sampling. As a result of this survey, despite the smallness of the
      sample, concern is raised regarding the application of public health information
      about IDD due to a taste preference for non-iodised salt, and the quality control
      of the manufacture of iodine-fortified salt.

PMID- 17518521
TI  - Bilateral leg swelling as the initial and predominant presentation of HIV and
      associated pulmonary arterial hypertension.
AB  - Although mortality from HIV has decreased over the last several years as a result
      of effective antiretroviral therapy, the infection continues to pose significant
      morbidity. Pulmonary arterial hypertension (PAH), for instance, has been reported
      to occur in the setting of established HIV infection on only rare occasions and
      carries a universally poor prognosis. The current case report is unique in
      describing a previously well patient who presents initially with complaints of
      debilitating leg swelling and is subsequently diagnosed with HIV and associated
      PAH.

PMID- 17518522
TI  - Antiretroviral therapies associated with lipoatrophy in HIV-infected women.
AB  - We previously demonstrated that HIV infection is associated with peripheral and
      central lipoatrophy in women. We now describe the association of specific
      antiretroviral drugs (ARV) with body fat changes over a four-year period from
      1999 to 2003. 775 HIV-positive and 205 HIV-negative women in the Women's
      Interagency HIV Study with anthropometric measurements, weight, bioelectric
      impedance analysis and ARV collected semiannually were included in analysis.
      Exposure to ARV was defined as report of use for 3 consecutive semiannual study
      visits. The average 6-month change in weight, percent total body fat, and
      circumference measurements (i.e., hip, waist, chest, arm, and thigh) was compared
      between those exposed and those unexposed to the specific ARV for any of the same
      three consecutive visits. Weight, percent total body fat, and hip, waist, thigh,
      chest, and arm circumferences decreased in HIV-positive women, but increased in
      HIV-negative women on average for every six-month interval over the 4-year study
      period. Among the HIV-positive women, didanosine was the only ARV associated with
      decreases in circumference measures in the hip (-0.65 cm, 95% confidence interval
      [CI]: -1.18, -0.12), waist (-0.71 cm, 95% CI: -1.37, -0.04), chest (-0.71 cm, 95%
      CI: -1.17, -0.26), and arm (-0.23 cm, 95% CI: -0.48, 0.03; p = 0.08). These
      prospective data suggest that fat loss continues to predominate in HIV-positive
      women and exposure to didanosine for at least 12 months may further worsen fat
      loss.

PMID- 17518523
TI  - A quantitative study on the condom-use behaviors of eighteen- to twenty-four-year
      old urban African American males.
AB  - This research study sought to develop, pilot test, and assess a brief male
      centered condom promotion program for urban young adult African American males.
      For study implementation, both qualitative and quantitative research methods were
      used, and the project was guided by tenets of two common but integrated
      theoretical frameworks in HIV/sexually transmitted disease (STD) prevention
      research: the social cognitive theory and the stages of change model. The purpose
      of the qualitative component was to identify and explore condom-use barriers and
      facilitators while that of the quantitative component was to identify the
      prevalence of condom-related behaviors and the feasibility of program
      administration. After recruitment of study participants from hang-out spots and
      street intercepts, study participants were self-administered a baseline survey
      regarding their perceived condom-use behaviors prior to random assignment to
      program conditions (a condom promotion program and an attention-matched
      comparison condition). In this paper, we report the findings from the analyses of
      the quantitative baseline survey data. While the occurrence of HIV/STD-related
      risk behavIors were highly prevalent among this population; importantly,
      regression analyses revealed that sexual debut, favorable attitudes toward condom
      use, social or personal connectedness to HIV/STDs, health beliefs, perceived
      susceptibility, unprotected sexual encounters, and refusal skills were predictive
      of retrospective (i.e., prior 30 days) condom use while positive reasons (pros)
      to use condoms, condom-use beliefs, condom-carrying, health belief, unprotected
      sexual encounters and refusal skills were also predictive of prospective (i.e.,
      future 30 days) condom-use intentions. The implications and limitations of this
      study are described and recommendations provided for program development.

PMID- 17518524
TI  - Gender differences in survival in an HIV/AIDS cohort from Sao Paulo, Brazil.
AB  - Highly active antiretroviral therapy accounted for significant improvement in
      AIDS prognosis. However, in areas where access to antiretrovirals is universal,
      the impact of treatment might have been less remarkable among women. To compare
      survival between men and women living with HIV, we studied a retrospective cohort
      of 1072 patients who attended a Brazilian reference center. Time to AIDS-related
      death was the dependent variable. Medical charts were reviewed to obtain
      sociodemographic data, clinical, and laboratory outcomes. Cumulative survival
      probability was estimated by the Kaplan-Meier method and hazard ratios by Cox
      proportional hazards model. At admission, 55% of men and 38% of women had AIDS.
      Ninety-one AIDS-related deaths occurred in 6004 person-years of follow-up (PYFU).
      After adjustment for antiretroviral therapy, predictors of death included: female
      gender (p = 0.02), age at HIV diagnosis (p = 0.005), lowest CD4 count less than
      200 cells/mm(3) (p < 0.001) and highest viral load greater than 100,000 copies
      per milliliter during follow-up (p = 0.007), having an AIDS-defining illness
      before admission or during follow-up (p < 0.001). We provide evidence that women
      have benefited less from care, though admitted to the clinic at earlier stages of
      HIV disease and offered standardised therapeutic interventions. However, the
      reasons for such gender differences in survival still remain unclear. Further
      studies are thus warranted to help recognize factors associated to a higher
      vulnerability in care among women, what may help establish strategies to enhance
      care for all people living with HIV and for women, in particular.

PMID- 17518525
TI  - Factors influencing the acceptance of changes in antiretroviral therapy among HIV
      1-infected patients.
AB  - Physicians routinely consider modifying antiretroviral therapy (ART) regimen for
      their patients with HIV. Little is known about the factors associated with
      patients' willingness to accept providers' recommended ART changes. This
      multicenter prospective observational study examined factors associated with
      willingness to accept ART changes recommended by their providers among HIV
      infected adults from six urban outpatient HIV clinics. Patients were surveyed
      using the Patient Attitudes about Altering Antiretroviral Therapy Survey
      questionnaire (PAAARTS). Factors associated with willingness to accept ART
      changes were assessed using a multivariate generalized estimating equation (GEE)
      model to account for correlated responses. The Classification and Regression
      Trees (CART) analysis was also performed to determine subgroups of patients with
      higher acceptance of change. 216 of 289 patients (75%) definitely accepted
      recommended changes. Odds for acceptance were 3.2, 2.3, and 2.8 times higher for
      patients with higher attitudes and beliefs about ART (p < 0.01; 95% confidence
      interval [CI] = 1.59, 6.52), patients who rated their provider's care as
      excellent (p < 0.05; 95% CI = 1.07, 4.78), and non-Hispanic patients (p < 0.05;
      95% CI 1.03, 7.57), respectively. CART analysis showed similar results and
      identified that when patients had less positive attitude about ART, acceptance
      rates were higher for non-Hispanic patients with higher assessments of their
      patient-provider communication. While most patients accepted providers'
      recommendation for ART changes, this willingness was influenced by both patients'
      attitudes and beliefs about ART and their assessment of either the effectiveness
      of patient-provider communication or their rating of providers' care. ART
      acceptance rates among Hispanic patients were lower.

PMID- 17518526
TI  - The health related quality of life outcomes of English and Spanish speaking
      persons living with HIV/AIDS from the continental United States and Puerto Rico.
AB  - Recent evidence indicates that HIV disproportionately affects ethnic minorities,
      youth, and women. The present study sought to further understand how
      sociodemographic and clinical factors impact the health-related quality of life
      (HRQL) of people living with HIV/AIDS (PLWHA) from the continental United States
      and Puerto Rico. Two hundred seventy-three participants (87% men, 13% women; 59%
      Hispanic, 25% black non-Hispanic, 16% white non-Hispanic) completed Spanish or
      English versions of the Functional Assessment of Human Immunodeficiency Virus
      Infection (FAHI), an illness-specific measure of HRQL. Univariate and
      multivariate regression analyses were performed using age, gender, ethnicity,
      level of education, insurance type, language preference, living arrangement,
      literacy level, antiretroviral status, CD4+ T cell count, and time since
      diagnosis as independent variables. Four subscales from the FAHI, physical,
      emotional, social, and functional/general well-being, were analyzed as dependent
      variables. Men and Spanish speaking participants reported better physical well
      being (p < 0.001). Men also reported better functional well-being (p < 0.05).
      Participants with a lower CD4+ T cell count, Spanish speakers, and White
      participants reported better emotional well-being (p < 0.001). Participants who
      lived with others, had a lower CD4+ T cell count, or were white reported better
      social well-being (p < 0.001). These results suggest that sociodemographic and
      clinical factors influence quality of life in PLWHA. Women appear to be
      particularly vulnerable to adverse quality of life impacts in the physical
      domains, and ethnic minorities appear vulnerable to adverse impacts in the
      psychosocial domains.

PMID- 17518527
TI  - Age difference in rates of mental health/substance abuse and behavioral care in
      HIV-positive adults.
AB  - This study aims to investigate age differences in rates of mental
      health/substance abuse and behavioral health treatment in HIV-positive adults.
      One-hundred and nine HIV-positive adults (21-88 years old) were recruited from
      the University of Pennsylvania Center for AIDS Research (CFAR) infectious disease
      clinics. Each subject participated in a 3-hour comprehensive
      behavioral/psychosocial interview. Over half of the sample displayed significant
      mental health and substance abuse symptoms, of which approximately a third were
      actively participating in behavioral health care. Major depression and illicit
      drug use appeared to be the most prevalent syndromes. However, individuals with
      mania and psychosis were most likely to be participating in behavioral health
      treatment, while individuals with at-risk drinking and illicit drug use were
      least likely to be participating in treatment. Furthermore, older-aged adults
      were less likely to be receiving behavioral health care when there was evidence
      of need. The findings of this investigation generally concluded that HIV-positive
      adults, especially older-aged adults, are in need of improved behavioral health
      management for mental health/substance abuse.

PMID- 17518528
TI  - Demographic, clinical, and virologic characteristics of African-born persons with
      HIV/AIDS in a Minnesota hospital.
AB  - Minnesota is currently home to the tenth largest African population and the
      second largest East African population in the United States. HIV is increasingly
      being diagnosed in African-born persons in Minnesota. A retrospective survey was
      conducted on all African-born patients in our HIV clinic between January 1994 and
      June 2005. We identified 237 patients who were African-born and HIV-positive.
      They constituted 12% of patients attending the clinic within the study timeframe.
      There was no significant difference in the ages of the African-born and non
      African patients in the HIV clinic. African-born patients were more likely to be
      women compared with non-African patients (p < 0.001). Forty-three percent of the
      African-born patients presented with AIDS as defined by CD4(+) T cell counts less
      than 200 cells per milliliter compared to 33% of antiretroviral naive non-African
      HIV patients in the clinic (p < 0.001). Most patients were infected through
      heterosexual contact and only 4% were diagnosed as a result of routine testing.
      Seven known HIV subtypes and four unique recombinant forms were identified. The
      most common opportunistic infection was pulmonary tuberculosis. African
      immigrants with HIV appear to: (1) access care at later stages of HIV disease
      than other patients in our clinic; (2) are often infected with non-B subtypes;
      (3) do not routinely get tested for HIV. Increased awareness to this growing
      trend is needed for health care providers and public health officials to tailor
      educational programs and prevention efforts for African immigrants in the United
      States.

PMID- 17518529
TI  - Abbott agrees to expand access to Kaletra/Aluvia.

PMID- 17518530
TI  - PROVE data released on telaprevir.

PMID- 17518531
TI  - Diffuse axonal injury in severe traumatic brain injury visualized using high
      resolution diffusion tensor imaging.
AB  - Traumatic brain injury (TBI) is the most common cause of death and disability in
      young people. The functional outcome in patients with TBI cannot be explained by
      focal pathology alone, and diffuse axonal injury (DAI) is considered a major
      contributor to the neurocognitive deficits experienced by this group. The aim of
      the present study was to investigate whether diffusion tensor imaging (DTI)
      offers additional information as to the extent of damage not visualized with
      standard magnetic resonance imaging (MRI) in patients with severe TBI. Nine
      chronic male TBI patients and 11 matched healthy controls were recruited. Results
      of the voxel-based analysis of fractional anisotropy (FA) maps and apparent
      diffusion coefficient (ADC) maps revealed significant differences in anisotropy
      in major white matter tracts, including the corpus callosum (CC), internal and
      external capsule, superior and inferior longitudinal fascicles, and the fornix in
      the TBI group. The FA and ADC measurements offered superior sensitivity compared
      to conventional MRI diagnosis of DAI. Region-of-interest (ROI) analyses confirmed
      these results in the investigated regions. The findings of this study support the
      hypothesis that severe TBI is accompanied by DAI. The DTI changes were more
      prominent on the right side that contained the focal pathology in most of the
      patients and accurately reflected differences in both hemispheres. In conclusion,
      DTI holds great promise as a diagnostic tool to identify and quantify the degree
      of white matter injury in TBI patients.

PMID- 17518532
TI  - Longitudinal changes in global brain volume between 79 and 409 days after
      traumatic brain injury: relationship with duration of coma.
AB  - Neuropathological and experimental animal studies indicate that traumatic brain
      injury (TBI) results in long-term, neurodegenerative changes. Structural image
      evaluation using normalization of atrophy (SIENA) offers an automated analysis of
      the subtle changes in percent brain volume change (%BVC) associated with TBI. In
      the present study, SIENA was used to evaluate %BVC in individuals who had
      sustained a mild to severe TBI. We obtained three-dimensional (3D) T1-weighted
      anatomical magnetic resonance imaging (MRI) scans approximately 79 days and again
      409 days post-injury. TBI patients (n = 37) displayed significantly greater
      decline in %BVC (-1.43%) relative to a normal comparison group (+0.1%, n = 30).
      Greater %BVC was associated with longer duration of post-injury coma. These
      results confirm previous findings from cross-sectional studies and argue that the
      brain undergoes continued structural change for several months post-injury.

PMID- 17518533
TI  - Proteomic identification of oxidized mitochondrial proteins following
      experimental traumatic brain injury.
AB  - Experimental traumatic brain injury (TBI) results in a significant loss of
      cortical tissue at the site of injury, and in the ensuing hours and days a
      secondary injury exacerbates this primary injury, resulting in significant
      neurological dysfunction. The mechanism of the secondary injury is not well
      understood, but evidence implicates a critical role for mitochondria in this
      cascade. This mitochondrial dysfunction is believed to involve excitotoxicity,
      disruption of Ca(2+) homeostasis, production of reactive oxygen species (ROS),
      ATP depletion, oxidative damage of mitochondrial proteins, and an overall
      breakdown of mitochondrial bioenergetics. Although oxidative damage occurs
      following TBI, the identities of proteins undergoing oxidative modification after
      TBI have not been investigated. In the present study, we utilized the 3-h post
      injury controlled cortical impact model of experimental TBI in 20 young adult
      male Sprague-Dawley rats, coupled with proteomics to identify specific
      mitochondrial fraction proteins from the cortex and hippocampus that were
      oxidatively modified after TBI. We identified, from the cortex, pyruvate
      dehydrogenase, voltage-dependent anion channel, fumarate hydratase 1, ATP
      synthase, and prohibitin. From the hippocampus, we identified cytochrome C
      oxidase Va, isovaleryl coenzyme A dehydrogenase, enolase-1, and glyceraldehyde-3
      phosphate dehydrogenase as proteins that had undergone oxidative modification
      following TBI. In addition, we have also shown that, following TBI, there is a
      reduction in the activities of pyruvate dehydrogenase (PDH), complex I, and
      complex IV. These findings demonstrate that, following TBI, several proteins
      involved in mitochondrial bioenergetics are highly oxidatively modified, which
      may possibly underlie the massive breakdown of mitochondrial energetics and
      eventual cell death known to occur in this model. The identification of these
      proteins provides new insights into the mechanisms that take place following TBI
      and may provide avenues for possible therapeutic interventions after TBI.

PMID- 17518534
TI  - Apolipoprotein E4 allele presence and functional outcome after severe traumatic
      brain injury.
AB  - Presence of the apolipoprotein E (APOE) 4 allele has been associated with
      increased incidence and faster progression of neurodegenerative diseases, poorer
      recovery from neurologic insult, and decreased cognitive function in the well
      elderly. The specific association between APOE genotype and recovery from severe
      traumatic brain injury (TBI) is conflicting with many groups finding the APOE 4
      allele to be associated with poorer outcome while others have found no
      association. The purpose of this study was to investigate the association between
      APOE 4 allele presence and recovery during the two years after injury from severe
      TBI in light of other potential covariates, such as age, race, gender,
      hypotension or hypoxia before hospital admission and severity of injury. APOE
      genotype was determined for 123 subjects with severe TBI. Glasgow outcome score
      (GOS) and mortality were collected at 3, 6, 12, and 24 months after injury.
      Results showed individuals improved over the two year period following injury and
      those with the 4 allele had a slower recovery rate than those without the APOE 4
      allele over the two year period. We did not however find significant differences
      in GOS at individual time points when controlling for other covariates. Our
      findings suggest that APOE 4 allele presence influences recovery rate from severe
      TBI independent of other covariates. The findings of this study are unique in
      that they address not only the relationship between APOE 4 allele presence and
      outcome from severe TBI, but also describe differences in trajectory of recovery
      by APOE 4 allele presence.

PMID- 17518535
TI  - Post-Injury Administration of Mitochondrial Uncouplers Increases Tissue Sparing
      and Improves Behavioral Outcome following Traumatic Brain Injury in Rodents.
AB  - Following experimental traumatic brain injury (TBI), a rapid and significant
      necrosis occurs at the site of injury which coincides with significant
      mitochondrial dysfunction. The present study is driven by the hypothesis that TBI
      induced glutamate release increases mitochondrial Ca(2+)cycling/overload,
      ultimately leading to mitochondrial dysfunction. Based on this premise,
      mitochondrial uncoupling during the acute phases of TBI-induced excitotoxicity
      should reduce mitochondrial Ca(2+) uptake (cycling) and reactive oxygen species
      (ROS) production since both are mitochondrial membrane potential dependent. In
      the present study, we utilized a cortical impact model of TBI to assess the
      potential use of mitochondrial uncouplers (2,4-DNP, FCCP) as a neuroprotective
      therapy. Young adult male rats were intraperitoneally administered vehicle
      (DMSO), 2,4-DNP (5 mg/kg), or FCCP (2.5 mg/kg) at 5 min post-injury. All animals
      treated with the uncouplers demonstrated a significant reduction in the amount of
      cortical damage and behavioral improvement following TBI. In addition,
      mitochondria isolated from the injured cortex at 3 or 6 h post-injury
      demonstrated that treatment with the uncouplers significantly improved several
      parameters of mitochondrial bioenergetics. These results demonstrate that post
      injury treatment with mitochondrial uncouplers significantly (p < 0.01) increases
      cortical tissue sparing ( approximately 12%) and significantly (p< 0.01) improves
      behavioral outcome following TBI. The mechanism of neuroprotection most likely
      involves the maintenance of mitochondrial homeostasis by reducing mitochondrial
      Ca(2+) loading and subsequent mitochondrial dysfunction. These results further
      implicate mitochondrial dysfunction as an early event in the pathophysiology of
      TBI and that targeting acute mitochondrial events can result in long-term
      neuroprotection and improve behavioral outcome following brain injury.

PMID- 17518536
TI  - Mechanical heterogeneity of the rat hippocampus measured by atomic force
      microscope indentation.
AB  - Knowledge of brain tissue mechanical properties may be critical for formulating
      hypotheses about traumatic brain injury (TBI) mechanisms and for accurate TBI
      simulations. To determine the local mechanical properties of anatomical
      subregions within the rat hippocampus, the atomic force microscope (AFM) was
      adapted for use on living brain tissue. The AFM provided advantages over
      alternative methods for measuring local mechanical properties of brain because of
      its high spatial resolution, high sensitivity, and ability to measure live
      samples under physiologic conditions. From AFM indentations, a mean pointwise or
      depth-dependent apparent elastic modulus, E, was determined for the following
      hippocampal subregions: CA1 pyramidal cell layer (CA1P) and stratum radiatum
      (CA1SR), CA3 pyramidal cell layer (CA3P) and stratum radiatum (CA3SR), and the
      dentate gyrus (DG). For all regions, E was indentation-depth-dependent,
      reflecting the nonlinearity of brain tissue. At an indentation depth of 3microm,
      E was 234 +/- 152 Pa for CA3P, 308 +/- 184 Pa for CA3SR, 137 +/- 97 Pa for CA1P,
      169 +/- 52 Pa for CA1SR, and 201 +/- 133 Pa for DG (mean +/- SD). Our results
      demonstrate for the first time that the hippocampus is mechanically
      heterogeneous. Based on our findings, we discuss hypotheses accounting for
      experimentally observed patterns of hippocampal cell death, which can be tested
      with biofidelic finite element models of TBI.

PMID- 17518537
TI  - FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited to
      membrane rafts after spinal cord injury.
AB  - The Fas/CD95 receptor-ligand system plays an essential role in apoptosis that
      contributes to secondary damage after spinal cord injury (SCI), but the mechanism
      regulating the efficiency of FasL/Fas signaling in the central nervous system
      (CNS) is unknown. Here, FasL/Fas signaling complexes in membrane rafts were
      investigated in the spinal cord of adult female Fischer rats subjected to
      moderate cervical SCI and sham operation controls. In sham-operated animals, a
      portion of FasL, but not Fas was present in membrane rafts. SCI resulted in FasL
      and Fas translocation into membrane raft microdomains where Fas associates with
      the adaptor proteins Fas-associated death domain (FADD), caspase-8, cellular FLIP
      long form (cFLIPL ), and caspase-3, forming a death-inducing signaling complex
      (DISC). Moreover, SCI induced expression of Fas in clusters around the nucleus in
      both neurons and astrocytes. The formation of the DISC signaling platform leads
      to rapid activation of initiator caspase-8 and effector caspase-3, and the
      modification of signaling intermediates such as FADD and cFLIP(L) . Thus,
      FasL/Fas-mediated signaling after SCI is similar to Fas expressing Type I cell
      apoptosis.

PMID- 17518538
TI  - Transplantation of adult rat spinal cord stem/progenitor cells for spinal cord
      injury.
AB  - Stem/progenitor cells derived from the ependymal region of the spinal cord have
      the ability to self-renew and are multipotential for neurons and glia. These
      cells may have the ability to regenerate the injured mammalian spinal cord as
      they do in some lower vertebrates. However, the optimal conditions for
      transplantation and the fate of transplanted cells are not fully known. In the
      current study, spinal cord stem/progenitor cells were cultured from adult male
      rats expressing enhanced green fluorescent protein (eGFP). Neurospheres were
      transplanted at the time of clip compression injury (35-g force) into the injury
      site, or 1 mm rostral and caudal to the injury site. Neurospheres were also
      transplanted into a subacute model (day 9 after injury) and a chronic model (day
      28 after injury). Functional recovery was also studied in an acute injury model
      with weekly locomotor testing over a 16-week period. A significant increase in
      cell survival at 7 days was seen in rats receiving rostral and caudal injections
      as compared to injection directly into the site of injury. A significant increase
      in cell survival was also seen in rats receiving subacute transplants at 9 days
      after injury. Transplanted cells differentiated primarily into astrocytes (31.2%)
      and oligodendrocytes (50.3%), and a small number of neurons (1%). No improvement
      was seen in the Basso, Beattie and Bresnahan (BBB) locomotor rating scale after
      acute transplantation as compared with injury only, although surviving
      transplanted cells were identified that had migrated across the injury site from
      the rostral and caudal injection sites.

PMID- 17518539
TI  - Simultaneous application of two neurotrophic factors after spinal cord injury.
AB  - We have studied the application of voltage gradients to injured spinal cord which
      enhanced regeneration of axons and reduced their retrograde degeneration after
      injury. This led to an implanted electronic device producing electrical fields
      sufficient to induce regeneration in both ascending and descending tracts of
      white matter (called oscillating field stimulation [OFS]), which has been
      associated with behavioral recovery in animal models of spinal cord injury (SCI).
      OFS has also proven to benefit neurologically complete spinal cord injured dogs
      and humans in clinical trials. These studies, however, have failed to confirm
      benefit if applied after the sub-acute period of SCI. Here we report on combining
      OFS with the application of a non-toxic neurotrophic factor, inosine, using a
      behavioral model for "chronic" SCI, the cutaneous trunci muscle (CTM) reflex in
      adult guinea pigs. Inosine was delivered subcutaneously in guinea pigs for 28
      days using implantable "osmotic pumps"--alone or in combination with OFS. In all
      animals, experimental and control treatments were withheld for three months after
      a right lateral hemisection of the thoracic spinal cord. Both inosine and the
      combination therapy produced a statistically significant recovery of CTM
      receptive fields silenced permanently by spinal cord hemisection in controls-
      though the combination therapy enhanced the time of the appearance of recovered
      regions of skin. Retransection of the cord in three recovered animals eliminated
      the CTM recovery confirming changes in neural connections were restricted to the
      cord and not due to changes in cutaneous peripheral innervation. Morphometry of
      anterogradely labeled white matter revealed a statistically enhanced regeneration
      of ascending and descending projections in animals treated with the combination
      "therapy" compared to inosine alone. These data suggest that combining
      neurotrophic factors of differing modes of action likely enhance the outcome from
      "chronic" SCI.

PMID- 17518540
TI  - Quantitative characterization of regenerating axons after end-to-side and end-to
      end coaptation in a rat brachial plexus model: a retrograde tracer study.
AB  - The efficacy of end-to-side repair as a method of nerve reconstruction has been
      questioned, and most studies that characterize the mode of re-innervation are
      marred by inappropriate experimental design and lack quantitative analysis. This
      makes characterization of re-innervating neurons confusing and consequently
      controversy remains as to the extent and source of reinnervating axons. In an
      experimental brachial plexus rat model, we transected the musculocutaneous nerve,
      labeled its neuron pool with Fast-Blue and joined the distal stump to the side of
      the intact ulnar nerve, or to the proximal stump of the divided ulnar nerve, to
      characterize neurons that reinnervate the recipient nerve. Tetramethyl-rhodamine
      dextran (TMRD) or fluoro-gold was used to map the reinnervating motor and sensory
      neurons at 12 weeks post-transection. No neurons originally labeled from
      musculocutaneous nerve were subsequently labeled with TMRD or fluoro-gold,
      showing that this original neuron pool does not contribute to re-innervation of
      the distal musculocutaneous nerve, but that reinnervation occurs solely by ulnar
      nerve motor and sensory axons. In the end-to-side group, 16.4% of the motor and
      7% of the sensory donor ulnar nerve neurons re-innervated the musculocutaneous
      nerve exclusively, and a further 10% motor and 11.6% sensory innervated the
      musculocutaneous nerve by collateral sprouting of their axons. This compared to
      re-innervation by 62.6% of motor and 70.4% of ulnar nerve sensory neurons in the
      positive control that underwent end-to-end repair. Our results confirm the
      concept of collateral sprouting and support the use of end-to-side repair.

PMID- 17518541
TI  - Suture of transected nerve suppresses expression of BH3-only protein Noxa in
      nerve-transected motor neurons of C57BL/6J mouse.
AB  - Disrupted peripheral nerves are typically sutured as spontaneous recovery does
      not always occur. However, the molecular mechanisms involved in nerve
      regeneration following end-to-end nerve suture are obscure. Here, we investigated
      effects of end-to-end nerve suture after peripheral nerve transection on motor
      neurons, using the C57BL/6J mouse hypoglossal nerve injury model. In this animal
      model, 60-80% of injured motor neurons gradually progress to neuronal death,
      while the remaining injured neurons survive and regenerate. Mice were divided
      into the Cut and Suture groups. In the Cut group, the right hypoglossal nerve was
      transected. In the Suture group, the right hypoglossal nerve was transected and
      then was repaired using end-to-end nerve suture. We assessed differences between
      the Cut and Suture groups by analyzing the neuronal survival rate by thionine
      staining and the nerve terminal regeneration rate by vesicular acetylcholine
      transporter (VAChT) immunohistochemistry, which is a marker for cholinergic
      presynaptic terminal. We found that 82.9% of motor neurons survived in the Suture
      group, whereas only 39.2% of motor neurons did in the Cut group 56 days after
      surgery. At that time point, 86% of presynaptic terminals compared to controls
      were regenerated in the Suture group, and 21% were regenerated in the Cut group.
      These results demonstrate that peripheral nerve suture prevented death of nerve
      transected motor neurons and promoted nerve regeneration. We also examined
      expression profiles of major survival and death signal-associated genes in
      hypoglossal nuclei using in situ hybridization and real-time polymerase chain
      reaction (PCR). Although most of the survival- and death-associated genes were
      regulated in a similar manner in both groups, expression of BH3-only protein Noxa
      mRNA was significantly lower in the Suture than in the Cut group. A significant
      suppression of Noxa expression by the Suture may be a major reason why nerve
      suture induces survival and regeneration of nerve-injured motor neurons.

PMID- 17518542
TI  - Aging delays the regeneration process following sciatic nerve injury in rats.
AB  - The present study investigated the effect of aging on muscle reinnervation in
      rats following a crush nerve injury. Using confocal laser scanning microscopy, we
      examined the spatial correlation of terminal Schwann cells (TSCs) or axon
      terminals with acetylcholine receptor (AChR) sites at neuromuscular junctions
      (NMJs). Compared to young rats (4 months of age), aged rats (24 months of age)
      demonstrated damaged TSC extensions and delayed regeneration. Post-injury
      endplate abnormalities in aged rats correlated with the degree of TSC
      degeneration. In the late stages of reinnervation, pathologic changes were seen
      in old rats, including multiple innervations, terminal sprouting, and poorly
      formed collateral innervation in NMJs. Our results suggest that the impaired TSC
      axon interaction in aged rats delays the reinnervation process.

PMID- 17518543
TI  - Protective effects of NIM811 in transient focal cerebral ischemia suggest
      involvement of the mitochondrial permeability transition.
AB  - Cerebral ischemia followed by reperfusion activates numerous pathways that lead
      to cell death. One such pathway involves the release of large quantities of the
      excitatory amino acid glutamate into the synapse and activation of N-methyl-D
      aspartate receptors. This causes an increase in mitochondrial calcium levels
      ([Ca(2+)](m)) and a production of reactive oxygen species (ROS), both of which
      may induce the mitochondrial permeability transition (MPT). As a consequence,
      there is eventual mitochondrial failure culminating in either apoptotic or
      necrotic cell death. Thus, agents that inhibit MPT might prove useful as
      therapeutic interventions in cerebral ischemia. In this study, we have
      investigated the neuroprotective efficacy of the novel compound NIM811. Similar
      in structure of its parent compound cyclosporin A, NIM811 is a potent inhibitor
      of the MPT. Unlike cyclosporin A, however, it is essentially void of
      immunosuppressive actions, allowing the role of MPT to be clarified in
      ischemia/reperfusion injury. The results of these studies demonstrate that NIM811
      provides almost 40% protection in a model of transient focal cerebral ischemia.
      This was associated with a nearly 10% reduction in mitochondrial reactive species
      formation and 34% and 38% reduction of cytochrome c release in core and penumbra,
      respectively. Treatment with NIM811 also increased calcium retention capacity by
      approximately 20%. Interestingly, NIM811 failed to improve ischemia-induced
      impairment of bioenergetics. The neuroprotective effects of NIM811 were not due
      to drug-induced alterations in cerebral perfusion after ischemia. Activation of
      MPT appears to be an important process in ischemia/reperfusion injury and may be
      a therapeutic target.

PMID- 17518544
TI  - End-to-side nerve repair in peripheral nerve injury.
AB  - In peripheral nerve injury, end-to-side neurorrhaphy has been reported as an
      alternative in cases that the proximal nerve stump is not accessible. Several
      hypotheses have been proposed to explain peripheral nerve regeneration after end
      to-side neurorrhaphy. Recent evidence suggests that nerve regeneration occurs by
      collateral sprouting. Although a great number of humoral factors have been
      identified, molecular mechanism of nerve regeneration after end-to-side
      neurorrhaphy has not been completely clarified yet. The goal of this technique is
      to provide satisfactory functional recovery for the recipient nerve, without any
      deterioration of the donor nerve function. End-to-side technique has been
      investigated in detail in both experimental and clinical studies. Only a limited
      number of reported cases in clinical practice, until today, can reveal that end
      to-side technique may become a viable means of repairing peripheral nerves in
      certain clinical situations.

PMID- 17518546
TI  - Allotopic mRNA localization to the mitochondrial surface rescues respiratory
      chain defects in fibroblasts harboring mitochondrial DNA mutations affecting
      complex I or v subunits.
AB  - The possibility of synthesizing mitochondrial DNA (mtDNA)-coded proteins in the
      cytosolic compartment, called allotopic expression, provides an attractive option
      for genetic treatment of human diseases caused by mutations of the corresponding
      genes. However, it is now appreciated that the high hydrophobicity of proteins
      encoded by the mitochondrial genome represents a strong limitation on their
      mitochondrial import when translated in the cytosol. Recently, we optimized the
      allotopic expression of a recoded ATP6 gene in human cells, by forcing its mRNA
      to localize to the mitochondrial surface. In this study, we show that this
      approach leads to a long-lasting and complete rescue of mitochondrial dysfunction
      of fibroblasts harboring the neurogenic muscle weakness, ataxia and retinitis
      Pigmentosa T8993G ATP6 mutation or the Leber hereditary optic neuropathy G11778A
      ND4 mutation. The recoded ATP6 gene was associated with the cis-acting elements
      of SOD2, while the ND4 gene was associated with the cis-acting elements of COX10.
      Both ATP6 and ND4 gene products were efficiently translocated into the
      mitochondria and functional within their respective respiratory chain complexes.
      Indeed, the abilities to grow in galactose and to produce adenosine triphosphate
      (ATP) in vitro were both completely restored in fibroblasts allotopically
      expressing either ATP6 or ND4. Notably, in fibroblasts harboring the ATP6
      mutation, allotopic expression of ATP6 led to the recovery of complex V enzymatic
      activity. Therefore, mRNA sorting to the mitochondrial surface represents a
      powerful strategy that could ultimately be applied in human therapy and become
      available for an array of devastating disorders caused by mtDNA mutations.

PMID- 17518547
TI  - When we were comrades together: a note on the language of assessment.
AB  - From a psychoanalytic perspective, the assessor is seen as more than a gatherer
      of data; he or she is viewed as a source of information independent of the tests
      as well as a potential vehicle of change. To effect these functions, the assessor
      needs to pay close attention to the language he or she uses in interaction with
      the patient. In this article, I present a case and then discuss it in terms of
      the role of language in the assessor-patient relationship: specifically, how the
      language used facilitated the establishing of a working alliance, the promoting
      of a meaningful dialogue, and eventually led to a deeper understanding of the
      patient.

PMID- 17518548
TI  - Using reliability generalization methods to explore measurement error: an
      illustration using the MMPI-2 PSY-5 scales.
AB  - Reliability generalization (RG) is a meta-analytic technique that allows for the
      systematic examination of variation in score reliability for different samples of
      test takers; this procedure is based on the recognition that reliability is not a
      stable property of a test but is sample dependent. As a demonstration of an RG
      analysis, I obtained 63 reliability coefficients for each of the MMPI-2 (Butcher
      et al., 2001) Personality Psychopathology 5 (Harkness, McNulty, & Ben-Porath,
      1995) scales. The overall variability of alpha coefficients supports the argument
      that reliability is sample dependent and underscores the need for researchers to
      calculate reliability estimates based on their research samples rather than
      simply citing published alpha coefficients as evidence of score reliability. I
      observed statistically significant mean reliability differences for scores across
      the 5 scales, with the highest level of reliability observed for scores on the
      measure of Negative Emotionality and the lowest levels of reliability observed
      for scores on the measures of Aggression and Disconstraint. There was no evidence
      that the sex-composition of a sample was systematically related to score
      reliability, and there were no statistically significant differences in
      reliability between scores obtained with the English version of the test and
      those obtained with translated forms. However, reliability was consistently lower
      for scores on some scales when the data were obtained in nonclinical settings as
      opposed to clinical ones. Sample size was not significantly correlated with
      reliability estimates. RG methods have the potential for deepening the level of
      understanding about the role of reliability in the evaluation and use of
      personality tests.

PMID- 17518549
TI  - The utility of the NEO-PI-R validity scales to detect response distortion: a
      comparison with the MMPI-2.
AB  - In this psychometric study, we compared the recently developed Validity Scales
      from the Revised NEO Personality Inventory (NEO PI-R; Costa & McCrae, 1992b) with
      the MMPI-2 (Butcher, Dahstrom, Graham, Tellegen, & Kaemmer, 1989) Validity
      Scales. We collected data from clients (n = 74) who completed comprehensive
      psychological evaluations at a university-based outpatient mental health clinic.
      Correlations between the Validity Scales of the NEO-PI-R and MMPI-2 were
      significant and in the expected directions. The relationships provide support for
      convergent and discriminant validity of the NEO-PI-R Validity Scales. The percent
      agreement of invalid responding on the two measures was high, although the
      diagnostic agreement was modest (kappa = .22-.33). Finally, clients who responded
      in an invalid manner on the NEO-PI-R Validity Scales produced significantly
      different clinical profiles on the NEO-PI-R and MMPI-2 than clients with valid
      protocols. These results provide additional support for the clinical utility of
      the NEO-PI-R Validity Scales as indicators of response bias.

PMID- 17518550
TI  - Development and preliminary validation of a Chinese version of the Buss-Perry
      Aggression Questionnaire in a population of Hong Kong Chinese.
AB  - I developed a Chinese version of the Aggression Questionnaire (Buss & Perry,
      1992) by translating scale items into Chinese and subjecting them to standard
      validation procedures. I used confirmatory factor analysis via structural
      equation modeling to compare several measurement models. Models based on Buss and
      Perry's (1992) original four-factor (29-item) scale failed to replicate in the
      Chinese sample; however, the construct validity of Bryant and Smith's (2001)
      abridged version of the Aggression Questionnaire received strong overall support.
      The new 12-item scale demonstrated good fit to the data and adequate internal
      reliability. Evidence for criterion validity was provided by the scale's
      sensitivity to differing levels of aggression in males and females. Convergent
      and discriminant validity received partial support from the pattern of
      correlations with a measure of anger rumination. Linguistic and metric
      equivalence were supported by high correlation coefficients between scores on
      Chinese and English versions of the scale completed by bilingual Chinese on
      separate occasions. Consistent replications of these preliminary results across
      three independent samples suggest that the Chinese version of the Aggression
      Questionnaire may be useful for clinical assessment and cross-cultural research.

PMID- 17518551
TI  - The structure of retrospective accounts of family environments: related to the
      structure of personality attributes.
AB  - Environmental variables are often assumed to constitute a qualitatively different
      domain from personality variables, and unlike personality variables, their
      structure is relatively poorly understood. We studied retrospective descriptions
      of families-of-origin in 3 samples using the items of Moos's (1974) Family
      Environment Scale (FES). Using cluster-analytic procedures, we generated a new
      set of 22 homogeneous item clusters for the FES at a level more specific than the
      10 conventional FES scales, thus enhancing potential fidelity in the measurement
      of family environments. We show that these item composites are well organized
      under a 3-factor structure and that reports of family environments on these 3
      factors correlate moderately with those of the Big Five personality factors that
      have the most analogous content. Results suggest possible homology between the
      structure of family environments and the structure of personality dispositions.

PMID- 17518552
TI  - Assessing self-critical perfectionism in clinical depression.
AB  - Several facets of perfectionism have been strongly associated with depression and
      anxiety. Dunkley and Blankstein (2000) combined these maladaptive traits with
      self-criticism to create a general construct labeled self-critical perfectionism.
      In this study, we employed confirmatory factor analysis to evaluate a model for
      assessing self-critical perfectionism in a clinically depressed sample using
      scales from 3 instruments. Participants were 356 depressed adult outpatients who
      completed 2 multidimensional measures of perfectionism and a measure of self
      criticism. A confirmatory factor model that separated a self-critical
      perfectionism construct from a more adaptive, achievement-striving component of
      perfectionism was supported. A composite scale assessing self-critical
      perfectionism demonstrated much larger correlations with distress measures
      compared to a composite scale assessing achievement striving and also showed
      evidence of discriminant validity. In this study, we provided further support for
      the valid assessment of self-critical perfectionism and extended evidence for its
      assessment to a clinically depressed sample.

PMID- 17518553
TI  - Development of the Weight- and Body-Related Shame and Guilt scale (WEB-SG) in a
      nonclinical sample of obese individuals.
AB  - In this article, we present the evaluation of the psychometric properties of a
      new self-report measure of Weight- and Body-Related Shame and Guilt (WEB-SG). The
      main purpose of the study was to measure shame and guilt feelings separately in
      obese individuals and investigate differing behavioral and emotional correlates
      of these emotions. Altogether, 331 obese participants completed the WEB-SG and
      other established self-report measures. A subset of the participants completed a
      6-month follow-up. The WEB-SG proved to be internally consistent and temporally
      stable over a 6-month period. Regarding the factorial structure, a two-factor
      conceptualization was supported. The construct validity of the WEB-SG subscales
      was evidenced by a substantial overlap of common variance with related measures.
      The subscales Shame and Guilt showed differential correlation patterns to other
      scales. The WEB-SG is a brief, psychometrically sound measure for assessing body
      shame and guilt concerning weight control in obese individuals.

PMID- 17518554
TI  - Varying cautionary instructions, monetary incentives, and comorbid diagnostic
      training in malingered psychopathology research.
AB  - In this article, we combine two analogue experiments in which we empirically
      examined three malingering methodological issues in individuals trained and
      instructed to simulate posttraumatic stress disorder (PTSD) on the Trauma Symptom
      Inventory (TSI; Briere, 1995). In Experiment 1, we examined TSI scale effects of
      the following manipulations using a 2 x 2 design with 330 college students: (a)
      inclusion or exclusion of cautionary instructions regarding believability of
      participants' simulation and (b) different financial incentive levels. In
      Experiment 2, we examined comorbid psychiatric diagnostic training with 180
      college students who were either trained to simulate PTSD and comorbid major
      depressive disorder or trained to simulate only PTSD. Caution main effects were
      significant for all but two TSI Clinical Scales, incentive main effects and
      interactions were only significant for one Clinical scale each, and the
      comorbidity manipulation did not yield any scale differences. We discuss
      malingering research design implications regarding the use of cautionary
      instructions, financial incentive levels, and comorbid training.

PMID- 17518555
TI  - Psychometric properties of the Trait Emotional Intelligence Questionnaire: factor
      structure, reliability, construct, and incremental validity in a French-speaking
      population.
AB  - In this research, we investigated the psychometrical properties of the Trait
      Emotional Intelligence Questionnaire (TEIQue, Petrides & Furnham, 2003) in a
      French-speaking population. In summary, we found that (a) TEIQue scores were
      globally normally distributed and reliable; (b) the United Kingdom four-factor
      structure (well-being, self-control, emotionality, sociability) replicated in our
      data; (c) TEIQue scores were dependent on gender but relatively independent of
      age; (d) there was preliminary evidence of convergent/discriminant validity, with
      TEIQue scores being independent of nonverbal reasoning (Raven's [1976] matrices)
      but positively related to some personality dimensions (optimism, agreeableness,
      openness, conscientiousness) as well as inversely related to others (alexithymia,
      neuroticism); (e) there was also preliminary evidence of criterion validity, with
      TEIQue scores predicting depression, anxiety, and social support as well as
      future state affectivity and emotional reactivity in neutral and stressful
      situations; (f) TEIQue scores were susceptible to socially desirable responding;
      however, (g) TEIQue scores had incremental validity to predict emotional
      reactivity over and above social desirability, alexithymia, and the Five-factor
      model of personality. Such results constitute encouraging preliminary findings in
      favor of the use of the TEIQue.

PMID- 17518556
TI  - Might the Rorschach be a projective test after all? Social projection of an
      undesired trait alters Rorschach Oral Dependency scores.
AB  - The degree to which projection plays a role in Rorschach (Rorschach, 1921/1942)
      responding remains controversial, in part because extant data have yielded
      inconclusive results. In this investigation, I examined the impact of social
      projection on Rorschach Oral Dependency (ROD) scores using methods adapted from
      social cognition research. In Study 1, I prescreened 85 college students (40
      women and 45 men) with the ROD scale and a widely used self-report measure of
      dependency, the Interpersonal Dependency Inventory (IDI; Hirschfeld et al.,
      1977). Results show that informing participants who scored low on the IDI that
      they were in fact highly dependent led to significant increases in ROD scores; I
      did not obtain parallel ROD increases for participants who scored high on the IDI
      or for participants who received low-dependent feedback. In Study 2, I examined a
      separate sample of 80 prescreened college students (40 women and 40 men) and
      showed that providing low self-report participants an opportunity to attribute
      dependency to a fictional target person prior to Rorschach responding attenuated
      the impact of high-dependent feedback on ROD scores. These results suggest that
      projection played a role in at least one domain of Rorschach responding. I
      discuss theoretical, clinical, and empirical implications of these results.

PMID- 17518557
TI  - Reliability of the UCLA Loneliness Scale in opiate dependent individuals.
AB  - The purpose of this study was to examine the internal consistency and test-retest
      reliability of the self-report University of California, Los Angeles, Loneliness
      Scale (UCLA LS; Russell, 1996) in methadone maintenance patients at an urban
      university hospital. A diverse sample of 117 patient volunteers completed a
      standardized interview that included the UCLA LS. A total of 67 participants
      returned after a minimum of 14 days for a follow-up session to complete an
      identical assessment but with a different researcher. We examined internal
      consistency and test-retest reliability in the total sample and in groups
      stratified by gender, race, ethnicity, and education. Across strata, the UCLA LS
      showed adequate to high internal consistency and good to excellent test-retest
      reliability. The UCLA LS was highly correlated with a measure of perceived
      belonging, supporting criterion validity. Findings support the use of the UCLA LS
      with methadone maintenance patients.

PMID- 17518560
TI  - Mechanical conditioning of cell-seeded small intestine submucosa: a potential
      tissue-engineering strategy for tendon repair.
AB  - Our long-term objective is to enhance tendon repair by delivering cells on
      natural biologic scaffolds to the repair site. Clinical outcomes may be improved
      by first preconditioning these cell-seeded constructs in bioreactors to enhance
      their properties at implantation and to deliver cells expressing a desired
      phenotype. In this work, we have investigated the effect of in vitro mechanical
      conditioning on small-intestine submucosa (SIS) scaffolds seeded with primary
      tendon cells (tenocytes). SIS scaffolds (with and without cells) were conditioned
      under various loading regimes over a 2-week period. In vitro cyclic loading
      significantly increased the biomechanical properties (e.g., stiffness) of cell
      seeded SIS constructs (129.1 +/- 10.2%) from time 0. The stiffness change of
      cyclically loaded constructs without cells was 33.9 +/- 13.8% and of statically
      loaded constructs with cells was 34.0 +/- 15.2% and without cells was 33.4 +/-
      10.7%. In the cell-seeded groups, our data demonstrate a direct role (e.g., cell
      tensioning) for cells in construct stiffening. In addition, the initial stiffness
      of the cell-seeded, cyclically loaded constructs was found to be a strong
      predictor of the change in construct stiffness. Despite the mechanical integrity
      of these constructs being significantly less than native tendon, our data show
      that structural properties can be improved with in vitro mechanical conditioning.
      These data provide the basis for future studies investigating in vitro
      conditioning (mechanical, chemical) of cell-seeded ECM scaffolds and the use of
      such constructs for enhancing tendon repair in vivo.

PMID- 17518561
TI  - A reverse transfection technology to genetically engineer adult stem cells.
AB  - A new non-viral method of gene transfection was designed to enhance the level of
      gene expression for rat mesenchymal stem cells (MSCs). Pullulan was cationized
      using chemical introduction of spermine to prepare cationized pullulan of non
      viral carrier (spermine-pullulan). The spermine-pullulan was complexed with a
      plasmid deoxyribonucleic acid (DNA) of luciferase and coated on the surface of
      culture substrate together with Pronectin of artificial cell adhesion protein.
      MSCs were cultured and transfected on the complex-coated substrate (reverse
      transfection), and the level and duration of gene expression were compared with
      those of MSCs transfected by culturing in the medium containing the plasmid DNA
      spermine-pullulan complex (conventional method). The reverse transfection method
      enhanced and prolonged gene expression significantly more than did the
      conventional method. The reverse method permitted the transfection culture of
      MSCs in the presence of serum, in contrast to the conventional method, which gave
      cells a good culture condition to lower cytotoxicity. The reverse transfection
      was carried out for a non-woven fabric of polyethylene terephthalate (PET) coated
      with the complex and Pronectin using agitation and stirring culture methods. The
      two methods enhanced the level and duration of gene expression for MSCs
      significantly more than did the static method. It is possible that medium
      circulation improves the culture conditions of cells in terms of oxygen and
      nutrition supply and waste excretion, resulting in enhanced gene expression.

PMID- 17518562
TI  - Beta1 integrin expression pattern in transitional urothelium does not allow for
      efficient stem cell enrichment as in other epithelia.
AB  - With a lack of distinct stem cell markers, isolation of tissue-specific stem
      cells for tissue engineering and gene therapy is a great challenge. Beta
      (beta)(1) integrin expression has been used as a way of enriching for putative
      epithelial stem cells through rapid adhesion to collagen IV or flow cytometry.
      This is a first report of enrichment of putative urothelial stem cells using
      rapid adhesion and flow cytometric methods. We assessed our success by
      determining the clonogenic and proliferative potential of the isolated cells. We
      demonstrated that enrichment based on beta(1) integrin expression with flow
      cytometry yields highly clonogenic and proliferative urothelial cells, whereas
      the rapid adhesion method is not as efficient, possibly because of the unique
      nature of urothelium, a transitional epithelium, compared to results reported in
      stratified and columnar epithelia.

PMID- 17518563
TI  - Modulating the development of renal tubules growing in serum-free culture medium
      at an artificial interstitium.
AB  - Little information on the structural growth of renal tubules is available. A
      major problem is the technical limitation of culturing intact differentiated
      tubules over prolonged periods of time. Consequently, we developed an advanced
      culture method to follow tubule development. Isolated tissue containing renal
      progenitor cells was placed in a perfusion culture container at the interphase of
      an artificial polyester interstitium. Iscove's modified Dulbecco's medium without
      serum or protein supplementation was used for culture, and the culture period was
      13 days. Tissue growth was not supported by addition of extracellular matrix
      proteins. The development of tubules was registered on cryosections labeled with
      soybean agglutinin (SBA) and tissue-specific antibodies. Multiple SBA-labeled
      tubules were found when aldosterone was added to the culture medium. In contrast,
      culture without aldosterone supplementation displayed completely disintegrated
      tissue. The development of tubules depended on the applied aldosterone
      concentration. The use of 1 x 10(-6) M and 1 x 10(-7) M aldosterone produced
      numerous tubules, while application of 1 x 10(-8) M to 1 x 10(-10) M led to a
      continuous decrease and finally a loss of tubule formation. The development of
      labeled tubules in aldosterone-treated specimens took an unexpectedly long period
      of at least 8 days. The morphogenic effect of aldosterone appeared to be
      mineralocorticoid hormone-specific since spironolactone and canrenoate abolished
      the development. Finally, dexamethasone induced widely distributed cell clusters
      instead of tubules.

PMID- 17518564
TI  - Regenerative medicine bioprocessing: building a conceptual framework based on
      early studies.
AB  - This paper reviews early studies of regenerative medicine using human cells and
      engineered tissues progressing from a laboratory-centered manual procedure toward
      automated manufacture. It then examines the distinctive bioprocesses by which
      autologous human material must be produced, the degree of simplification allowed
      by use of allogeneic cell lines and engineered tissue derived from them, and
      issues that affect both cell types. The paper concludes by drawing upon this
      discussion to suggest some factors that will determine how regenerative medicine
      bioprocessing can progress to provide many units of material economically.

PMID- 17518565
TI  - Transplantation of genetically engineered mesenchymal stem cells improves cardiac
      function in rats with myocardial infarction: benefit of a novel nonviral vector,
      cationized dextran.
AB  - It is expected that mesenchymal stem cells (MSCs) will be a cell source for
      cardiac reconstruction because of their differentiation potential and ability to
      supply growth factors. However, poor viability at the transplanted site often
      hinders the therapeutic potential of MSCs. Here, in a trial designed to address
      this problem, a non-viral carrier of cationized polysaccharide is introduced for
      genetic engineering of MSCs. Spermine-introduced dextran of cationized
      polysaccharide (spermine-dextran) was internalized into MSCs by way of a sugar
      recognizable receptor to enhance the expression level of plasmid deoxyribonucleic
      acid (DNA). When genetically engineered by the spermine-dextran complex with
      plasmid DNA of adrenomedullin (AM), MSCs secreted a large amount of AM, an anti
      apoptotic and angiogenic peptide. Transplantation of AM gene-engineered MSCs
      improved cardiac function after myocardial infarction significantly more than
      MSCs alone. Thus, this genetic engineering technology using the non-viral
      spermine-dextran is a promising strategy to improve MSC therapy for ischemic
      heart disease.

PMID- 17518566
TI  - Chitosan microchannel scaffolds for tendon tissue engineering characterized using
      optical coherence tomography.
AB  - Tendon tissue engineering requires the generation of a uniaxially orientated
      collagen type I matrix with several organization scales that confer mechanical
      functionality upon the tendon. A combination of factors in a dose- and time
      dependent manner, such as growth factors and mechanical environment, may be the
      key to an in vitro-engineered tendon. To define the progress of tissue
      development within a scaffold, on-line systems need to be applied to monitor the
      newly generated matrix. To address this challenge, we designed a new porous
      chitosan scaffold with microchannels (diameter: 250 microm), which allows primary
      porcine tenocytes to proliferate in a bundle-like structure. The cell
      proliferation and extracellular matrix (ECM) production within the microchannels
      were successfully assessed under sterile conditions using optical coherence
      tomography (OCT). A semi-quantitative method that calculated the microchannel
      occupation ratio (the degree of cell proliferation and tissue turnover based on
      the total backscattered intensity in the microchannels) was developed. We further
      investigated the effect of different culture conditions on tendon cell matrix
      formation. Using a perfusion bioreactor, we demonstrated how fluid flow can
      increase (p < 1e(3)) ECM production within the microchannels significantly more
      than static culture. Our study illustrates how using a guiding scaffold in
      combination with the fast and non-destructive assessment of the microstructure
      using OCT allows discrimination between the parameters affecting the production
      and the organization of the ECM.

PMID- 17518567
TI  - Bone marrow stromal cells act as feeder cells for tendon fibroblasts through
      soluble factors.
AB  - Feeder effects of bone marrow stromal cells (BMSCs) on tendon fibroblasts were
      investigated using a co-culture method for the application of ligament or tendon
      tissue engineering and cell therapy. BMSCs had significant effects on enhancing
      cell proliferation, the ability of cells to migrate, and cell adhesivity but
      little effect on the extracellular matrix (ECM) synthesis of tendon fibroblasts
      without cell-cell contact. Furthermore, the conditioned medium from BMSCs,
      despite the existence of fibroblasts, significantly increased the number of
      fibroblasts. Based on these results, the mechanism of the feeder effects is
      considered to be a certain signal of soluble factors from BMSCs to the
      fibroblasts. Comparative proteome analysis of the conditioned medium from co
      culture of fibroblasts and BMSCs revealed less expression of plasminogen, which
      showed inhibitory effects on fibroblast proliferation. With regard to the
      relationships between plasminogen and BMSCs in the co-culture system, we
      speculate that BMSCs allow resolution of plasminogen or its cleavage activity in
      the medium via some mechanism.

PMID- 17518568
TI  - Evaluation of porcine aortic valve interstitial cell activity using different
      serum types in two- and three-dimensional culture.
AB  - Unlike established cell lines used in the biotechnology industry, primary cells
      used in tissue engineering require culture media to be supplemented with serum.
      The most common serum is fetal bovine serum (FBS); however, FBS is expensive,
      negatively affecting process economics. Less-costly alternative sera are
      commercially available, but their efficacy has not been documented. Therefore,
      bovine calf serum (BCS), bovine growth serum (BGS), and newborn calf serum (NCS)
      were compared with FBS. Porcine aortic valve interstitial cells (VICs) were
      cultured as 2-dimensional (2-D) monolayers or as 3-dimensional (3-D) collagen
      gels using medium supplemented with 10% FBS, BGS, BCS, or NCS. No significant
      difference was seen in cellular activity between VICs cultured in BCS and those
      cultured in FBS in 2-D cultures, whereas cells cultured in BGS and NCS had
      significantly lower specific growth rates coupled with markedly higher metabolic
      activity than cells cultured in FBS. No statistically significant differences
      were seen in cellular activity between any of the sera when cells were cultured
      in 3-D constructs. In conclusion, BCS is a suitable alternative to FBS for the 2
      D and 3-D culture of VICs, which may be used to develop a tissue-engineered
      valve.

PMID- 17518569
TI  - Preconditioning of mesenchymal stem cells with low-intensity ultrasound for
      cartilage formation in vivo.
AB  - The purpose of this study was to evaluate the benefits of in vitro
      preconditioning of mesenchymal stem cells (MSCs) using low-intensity ultrasound
      (US) in the induction of chondrogenic differentiation of MSCs in vivo. After
      rabbit bone marrow-derived MSCs were seeded onto a polyglycolic acid (PGA)
      scaffold, the PGA-MSCs constructs were divided into 4 subgroups: untreated
      control, low-intensity US group, transforming growth factor-beta [TGF]-treated
      group and low-intensity US/TGF group. The chondrocyte-seeded PGA construct served
      as a positive control. For 1 week before implantation, the low-intensity US
      groups were subjected to ultrasound treatment for 20 min daily at an intensity of
      200 mW/cm(2). The TGF groups were treated with 10 ng/mL TGF-beta1. The cells were
      then implanted into the nude mouse subcutaneously. Retrieved 1, 2, 4, and 6 weeks
      after implantation, each construct underwent gross examination, histology,
      biochemical assays, mechanical testing, and reverse transcriptase polymerase
      chain reaction (RT-PCR). Substantial size reduction and blood invasion were found
      much earlier in the groups that did not undergo low-intensity US than in those
      that did. Safranin O/Fast green staining revealed that the chondrogenic
      differentiation of MSCs was more widespread throughout the constructs in the low
      intensity US groups. In the biochemical and mechanical analyses, the low
      intensity US and low-intensity US/TGF groups were significantly better in forming
      hyaline cartilage-like tissue by 4 weeks than the non-low-intensity US groups.
      Presented by von Kossa staining, the development of osteogenic phenotypes was
      highly suppressed until 4 weeks in the low-intensity US groups, along with
      compressive strength comparable to the positive control. In the RT-PCR analysis
      before implantation, the messenger RNA levels of Sox-9, aggrecan, and tissue
      inhibitors of metalloproteinase-2 were higher in the low-intensity US groups,
      while those of type I and type X collagens and matrix metalloproteinase-13 were
      higher in the non-low-intensity US groups. Blood invasion into the constructs was
      also considerably hindered in the low-intensity US groups. These results strongly
      indicate that low-intensity US preconditioning in vitro could be an effective cue
      to upregulate chondrogenic differentiation of MSCs in vivo.

PMID- 17518570
TI  - Characterizing environmental factors that impact the viability of tissue
      engineered constructs fabricated by a direct-write bioassembly tool.
AB  - Tissue engineering combines the fields of medicine and engineering to build
      replacement tissue capable of restoring, maintaining, or improving damaged
      tissue. Researchers have recently developed techniques to fabricate tissue in
      which both the cells and matrix have a carefully defined architecture. This
      report details studies evaluating the use of a direct-write, 3-dimensional (3D)
      bioassembly tool (BAT) capable of extruding cells and matrix into spatially
      organized, 3D constructs. This system has been characterized by its ability to
      fabricate viable 2-dimensional and 3D constructs containing up to 2 separate
      cellular solutions suspended in type I collagen. The effects of various
      environmental factors, such as extrusion pressure, humidity, and stage heating,
      were examined with respect to the viability of the extruded cells. The data
      indicate that the system parameters required to extrude cells suspended in
      collagen do not adversely affect the viability of those cells. Maintaining a high
      humidity, especially when stage heat was applied, is critical in maintaining the
      viability of the printed cells. These results demonstrate that the BAT is capable
      of spatially organizing separate cellular solutions into a defined architecture;
      however, when cells were extruded in a supporting matrix of 3.0 mg/mL type I
      collagen, it was not possible to consistently generate adjacent, touching, but
      nonoverlapping lines of separate solutions. Thus, when a fabrication system such
      as BAT is used to generate complex, 3D viable constructs, the supporting matrix
      for the cells should be carefully chosen on the basis of such characteristics as
      its rate of polymerization and stiffness.

PMID- 17518571
TI  - In vitro enhancement of collagen matrix formation and crosslinking for
      applications in tissue engineering: a preliminary study.
AB  - The construction of stable engineered tissue depends on the formation of a
      functional connective tissue produced by cells locally. A major component of
      connective tissue is collagen. Its deposition into a stable matrix depends on the
      enzymatic extracellular conversion of procollagen to collagen. This step is very
      slow in vitro and we hypothesized that this is due to a lack of crowdedness and
      insufficient excluded volume effect (EVE) in culture media. We used neutral (670
      kDa) and negatively charged dextran sulfate (DxS, 500 kDa) to create EVE in cell
      cultures and to enhance in vitro matrix formation by accelerating procollagen
      conversion. Biochemical analyses in 2 human fibroblast lines revealed mostly
      unprocessed procollagen in uncrowded culture medium, whereas in the presence of
      DxS, procollagen conversion occurred and most of the collagen was associated with
      the cell layer. Immunocytochemistry confirmed DxS-related collagen deposition
      that colocalized with fibronectin. The large neutral dextran showed, in identical
      concentration ranges, no effects that correlated well with its smaller
      hydrodynamic radius as determined by dynamic light scattering. This predicted a
      10 times bigger crowding power of DxS and benchmarks it as a potentially
      promising crowding agent facilitating the formation of extracellular matrix in
      vitro.

PMID- 17518572
TI  - Gene expression profiling of cells involved in periodontal regeneration.
AB  - Understanding the molecular mechanisms involved in periodontal regeneration is
      important for the development of more predictable clinical techniques. This study
      aimed to identify these mechanisms by comparing the gene expression profiles of
      cells derived from regenerating defects with patient-matched periodontal ligament
      cells. Gene profiling was carried out via Affymetrix U133A arrays containing
      probes for 22,000 genes. Robust differences in gene expression were obtained by
      identifying genes that consistently changed by a minimum of 2-fold. Analysis of
      molecular function as designated by gene ontology (GO) identified differentially
      regulated mechanisms including protein metabolism, tyrosine kinase activity, and
      skeletal development. The differentially expressed genes could be broadly divided
      into the categories of protein biosynthesis and turnover, structural constituents
      of the cytoskeleton and extracellular matrix, and signal transduction. The
      differential expression of 4 genes (EGR-1, elastin, osteoprotegerin, and IGFBP3)
      was confirmed via real-time polymerase chain reaction (PCR). Further, the
      expression of another 2 differentially expressed transcripts, decorin and
      biglycan, was immunohistochemically confirmed in a periodontal wound healing
      model and the protein expression was consistent with the pattern of gene
      expression. This study gives insight into the molecular processes involved in
      periodontal regeneration and identifies cell markers that are characteristic of
      regenerating periodontal tissues.

PMID- 17518573
TI  - Bone increase in rat tibiae by local administration of amino-terminally truncated
      rhFGF-4(73-206).
AB  - Fibroblast growth factor 4 (FGF-4) plays important roles in bone development
      during embryogenesis. Human FGF-4 consists of 206 amino acid residues. We
      produced amino-terminally truncated rhFGF-4, named rhFGF-4(73-206), that
      increases bone mineral density when systemically administered to mice. In the
      present study, we examined the effects of rhFGF-4(73-206) in bone after local
      administration. We injected 1 microg of rhFGF-4(73-206) into tibiae of 10-week
      old Sprague-Dawley rats. At days 4 and 7, sets of animals were subjected for
      tibial bone marrow cell culture in an osteogenic medium. The bone marrow cells
      from FGF-4-injected tibiae produced more alkaline phosphatase-positive cells and
      mineralized nodules than those from control tibiae, indicating that local
      injection of rhFGF-4(73-206) increased the osteoblastic population in the bone
      marrow. The remaining sets of animals were killed on days 7 and 10. The tibiae
      were then analyzed with soft X-ray, dual energy X-ray absorptiometry, peripheral
      quantitative computed tomography, and histomorphometry. The radiographic analyses
      revealed increases in trabecular bone in the tibiae but no difference in the
      cortical bone between the rhFGF-4(73-206) group and the control group. High bone
      turnover and a derived increase of trabecular bone mineral density were
      demonstrated by histomorphometry in the rhFGF-4(73-206) group. The present
      results indicate that local injection with rhFGF-4(73-206) elicited an increase
      in the osteogenic cell population in the tibial bone marrow, which resulted in
      more trabecular bone.

PMID- 17518575
TI  - Tissue engineering: perspectives, challenges, and future directions.

PMID- 17518574
TI  - Tissue compatibility of interfacial polyelectrolyte complexation fibrous
      scaffold: evaluation of blood compatibility and biocompatibility.
AB  - Interfacial polyelectrolyte complexation (PEC) fiber has been proposed as a
      biostructural unit and biological construct for tissue engineering applications,
      with its ability to incorporate proteins, drug molecules, DNA nanoparticles, and
      cells. In this study, we evaluated the biocompatibility and blood compatibility
      of PEC fiber in order to assess its potential for in vivo applications in tissue
      engineering. Although chitosan-alginate PEC fibrous scaffold was found to be
      thrombogenic, the blood compatibility of the scaffold could be significantly
      improved by incorporating a small amount of heparin in the polyelectrolyte
      solution during fiber formation. The platelet microparticle production and
      platelet adhesion on the chitosan-alginate-heparin fibrous scaffold were
      comparable to those on the resting control. In vitro cytotoxicity test showed
      that the scaffold was not toxic to human mesenchymal stem cells (hMSCs). In the
      in vivo biocompatibility test in rats, no acute inflammation was observed in the
      subcutaneously or intramuscularly implanted specimens. Good cell infiltration and
      vascularization were observed after 2 months of implantations. Enhanced
      extracellular matrix (ECM) deposition was observed when hMSCs were cultured in
      the transforming growth factor-beta3 (TGF-beta3)-encapsulated PEC fibrous
      scaffold in vitro, or when the TGF-beta3-encapsulated PEC was implanted
      intramuscularly in vivo. The results showed that this versatile PEC fibrous
      scaffold could be used in various tissue engineering applications for its good
      biocompatible and blood compatible properties.

PMID- 17518576
TI  - A rapid and efficient method for expansion of human mesenchymal stem cells.
AB  - During the past decade, there has been much interest in the use of human
      mesenchymal stem cells (hMSCs) in bone tissue engineering. HMSCs can be obtained
      relatively easily and expanded rapidly in culture, but for clinical purposes
      large numbers are often needed and the cost should be kept to a minimum. A rapid
      and efficient culturing protocol would therefore be beneficial. In this study, we
      examined the effect of different medium compositions on the expansion and
      osteogenic differentiation of bone marrow-derived hMSCs from 19 donors. We also
      investigated the effect of low seeding density and dexamethasone on both hMSCs
      expansion and their in vitro and in vivo osteogenic differentiation capacity.
      HMSCs seeded at a density of 100 cells/cm2 had a significantly higher growth rate
      than at 5000 cell/cm2, which was further improved by the addition of
      dexamethasone. Expanded hMSCs were characterized in vitro on the basis of
      positive staining for CD29, CD44, CD105, and CD166. The in vitro osteogenic
      potential of expanded hMSCs was assessed by flow cytometric staining for alkaline
      phosphatase. In vivo bone-forming potential of the hMSCs was assessed by seeding
      the cells in ceramic scaffolds, followed by subcutaneous implantation in nude
      mice and histopathologic assessment of de novo bone formation after 6-week
      implantation. Expanded hMSCs from all donors displayed similar osteogenic
      potential independent of the culture conditions. On the basis of these results we
      have developed an efficient method to culture hMSCs by seeding the cells at 100
      cells/cm2 in an alpha-minimal essential medium-based medium containing
      dexamethasone.

PMID- 17518577
TI  - Bone regeneration on a collagen sponge self-assembled peptide-amphiphile
      nanofiber hybrid scaffold.
AB  - The objective of this study was to create a novel approach to promote bone
      induction through sustained release of growth factor from a 3-dimensional (3D)
      hybrid scaffold. Peptide-amphiphile (PA) was synthesized by standard solid-phase
      chemistry that ends with the alkylation of the NH2 terminus of the peptide.
      Collagen sponge was reinforced by incorporation of poly(glycolic acid) (PGA)
      fiber. A 3D network of nanofibers was formed by mixing basic fibroblast growth
      factor (bFGF) suspensions with dilute aqueous solutions of PA. A hybrid scaffold
      was fabricated by combination of self-assembled PA nanofibers and collagen sponge
      reinforced with incorporation of PGA fibers. The in vitro release profile of bFGF
      from hybrid scaffold was investigated, and ectopic bone formation induced by the
      released bFGF was assessed after subcutaneous implantation of hybrid scaffold
      into the backs of rats. Homogeneous bone formation was histologically observed
      throughout the hybrid scaffolds, in marked contrast to collagen sponge
      incorporated bFGF. The level of alkaline phosphatase activity and osteocalcin
      content at the implanted sites of hybrid scaffolds were significantly high
      compared with collagen sponge incorporated with bFGF. The combination of bFGF
      incorporated in a collagen sponge self-assembled PA nanofiber hybrid scaffold is
      a promising procedure to improve bone regeneration.

PMID- 17518578
TI  - Migration of the epidermal over the dermal component (epiboly) in a bilayered
      bioengineered skin construct.
AB  - A bilayered bioengineered living skin construct (LSC) consisting of viable human
      neonatal keratinocytes over a collagenous dermis seeded with dermal fibroblasts
      has been used extensively in difficult-to heal human wounds. Its biological
      properties include production of several mediators, cytokines, and growth factors
      and the ability to heal itself upon injury. In this study, we investigated the
      process of keratinocyte migration in LSC. At baseline, 6-mm punch biopsies of the
      construct were placed in serum-free medium (AIM-V) or Dulbecco's modified Eagle
      medium. At varying time points, the LSC samples were processed and analyzed using
      histology and immunohistochemistry. By 72 h, in a time-dependent manner, the
      overlying epidermis had migrated over and enveloped the entire underlying dermis,
      a process known as epiboly. Increasing concentrations of neutralizing antibodies
      to epidermal growth factor or interleukin-1 alpha down-regulated the extent of
      epiboly, as measured using computerized planimetry, but antibodies to
      transforming growth factor-beta 1 did not affect it. The consistent expression of
      laminin V, alpha3beta1 integrin, and vitronectin (epibolin) and its integrin
      receptor (alphavbeta5) characterized the tongue of migrating epidermis.
      Increasing concentrations of antibodies to vitronectin blocked the process of
      epiboly, as did antibodies to the alphavbeta5 integrin receptor, which mediates
      vitronectin-driven keratinocyte locomotion. This process of epiboly provides
      novel mechanisms of action for bioengineered skin constructs.

PMID- 17518579
TI  - Mechanical loading-dependence of mRNA expressions of extracellular matrices of
      chondrocytes inoculated into elastomeric microporous poly(L-lactide-co-epsilon
      caprolactone) scaffold.
AB  - The temporal response of young rabbit chondrocyte metabolism (including
      biosynthesis of extracellular matrix macromolecules such as collagen and
      aggrecan, both of which are essential components of normal cartilage tissue, and
      their messenger ribonucleic acid (mRNA) expression) in microporous elastomeric
      scaffolds made of poly(L-lactide-co-epsilon-caprolactone) subjected to different
      compressive regimes (loading frequency, loading duration per cycle, loading
      period, and continuous or intermittent compression) were studied over a 6-day
      culture period at 10% of compressive strain. A continuous dynamic compression
      improved the production of sulfated glycosaminoglycan (S-GAG), most of which was
      released into the culture medium upon loading. High mRNA expression of type II
      collagen was exhibited at a frequency of 0.1 Hz. Little frequency dependency was
      observed for aggrecan. An intermittent loading (24-h cycle of loading and
      unloading) or short loading and unloading duration per cycle-compression regime
      maintained high levels of mRNA expression. This strongly suggests that well
      controlled mechanical conditioning regimes may control the gene expression of key
      metabolic substances relevant to functional cartilage tissue while the degree of
      release of these substances into the culture medium is minimized.

PMID- 17518580
TI  - Synthesis of glycosaminoglycans in differently loaded regions of collagen gels
      seeded with valvular interstitial cells.
AB  - Cells respond to changes in mechanical strains by varying their production of
      extracellular matrix macromolecules. Because differences in strain patterns
      between mitral valve leaflets and chordae tendineae have been linked to different
      quantities and types of glycosaminoglycans (GAGs), we investigated the effects of
      various strain conditions on GAG synthesis by valvular interstitial cells (VICs)
      using an in vitro 3-dimensional tissue-engineering model. VICs from leaflets or
      chordae were seeded within collagen gels and subjected to uniaxial or biaxial
      static tension for 1 week. GAGs synthesized within the collagen gels and secreted
      into the surrounding medium were analyzed using fluorophore-assisted carbohydrate
      electrophoresis. In constrained conditions, more 4-sulfated GAGs were retained
      within the collagen gel, whereas more hyaluronan was secreted into the
      surrounding medium. Selected GAG classes were found in significantly different
      proportions in collagen gels seeded with leaflet cells versus chordal cells. The
      only significant difference between uniaxial and biaxial regions was found for 6
      sulfated GAGs in the gels seeded with chordal cells (p<0.05). This study suggests
      how mechanical loading may influence GAG production and localization in the
      remodeling of the mitral valve and has design implications for engineered
      tissues.

PMID- 17518581
TI  - Recapitulating development: a template for periodontal tissue engineering.
AB  - The induction of bone formation by the soluble osteogenic molecular signals of
      the transforming growth factor-beta (TGF-beta) superfamily is a critical issue to
      periodontologists, molecular biologists, and tissue engineers alike, because
      preclinical studies in primates and clinical trials have demonstrated the bone
      induction capacity of bone morphogenetic and osteogenic proteins (BMPs/OPs) in
      clinical context. BMPs/OPs, pleiotropic members of the TGF-beta superfamily,
      induce de novo endochondral bone formation as a recapitulation of embryonic
      development and act as soluble signals for tissue morphogenesis sculpting the
      multicellular mineralized structures of the periodontal tissues with functionally
      oriented periodontal ligament fibers inserting into newly formed cementum. This
      paper reviews the induction of the complex tissue morphologies of the periodontal
      tissues in the nonhuman primate Papio ursinus with furcation defects treated with
      doses of naturally derived and recombinantly produced human BMPs/OPs. Periodontal
      tissue regeneration develops as a mosaic structure in which the OPs of the TGF
      beta superfamily singly, synergistically, and synchronously initiate and maintain
      tissue induction and morphogenesis.

PMID- 17518582
TI  - Photochemical cross-linking for collagen-based scaffolds: a study on optical
      properties, mechanical properties, stability, and hematocompatibility.
AB  - Collagen presents an attractive biomaterial for tissue engineering because of its
      excellent biocompatibility and negligible immunogenicity. However, some intrinsic
      features related to the mechanical stability and thrombogenicity limit its
      applications in orthopedic and vascular tissue engineering. Photochemical cross
      linking is an emerging technique able to stabilize tissue grafts and improve the
      physicochemical properties of collagen-based structures. However, other important
      properties of collagen-based structures and the effect of processing parameters
      on these properties have not been explored. In this study, we aim to investigate
      the dose dependence of tensile and swelling properties on two parameters, namely,
      laser energy fluence and rose Bengal photosensitizer concentration. We also study
      the compression properties using cyclic compression test, long-term stability
      using subcutaneous implantation, and hematocompatibility using platelets adhesion
      test, of cross-linked collagen structures. Moreover, because limited optical
      penetration in turbid media is the major obstacle for light-based techniques, we
      also characterize the optical properties, which partially determine the effective
      optical penetration depth in collagen gel samples, during photochemical cross
      linking. Laser energy fluence and rose Bengal concentration are important
      parameters affecting the cross-linking efficiency, which was characterized as the
      mechanical and the swelling properties, in a dose-dependent manner. Under the
      experimental conditions in this study, the peak fluence was 12.5 J/cm2 and the
      minimal rose Bengal concentration for effective cross-linking was >0.00008%
      (0.786 micromol). Photochemical cross-linking also enhanced the compression
      strength and long-term stability of collagen structures without compromising the
      tissue compatibility. Furthermore, photochemical cross-linking reduced platelet
      adhesion and abolished fibrin mesh formation, thereby improving the
      hematocompatibility of collagen structures. These results suggest the feasibility
      of using the photochemically cross-linked collagen structures for orthopedic and
      vascular tissue engineering. Finally, the effective optical penetration depth in
      collagen gel samples is wavelength and rose Bengal concentration dependent, and
      was approximately 12 mm at 514 nm at 0.001% (9.825 micromol), the rose Bengal
      concentration mostly used in this study.

PMID- 17518583
TI  - Engineering of implantable cartilaginous structures from bone marrow-derived
      mesenchymal stem cells.
AB  - Fabrication of implantable cartilaginous structures that could be secured in the
      joint defect could provide an alternative therapeutic approach to prosthetic
      joint replacement. Herein we explored the possibility of using biodegradable
      hydrogels in combination with a polyglycolic acid (PGA) scaffold to provide an
      environment propitious to mesenchymal stem cells (MSCs) chondrogenic
      differentiation. We examined the influence of type I collagen gel and alginate
      combined with PGA meshes on the extracellular matrix composition of tissue
      engineered transplants. MSCs were isolated from young rabbits, expanded in
      monolayers, suspended in each hydrogel, and loaded on PGA scaffolds. All
      constructs (n=48) were cultured in serum-free medium containing transforming
      growth factor beta-1, under dynamic conditions in specially designed bioreactors
      for 3-6 weeks. All cell-polymer constructs had a white, shiny aspect, and
      retained their initial size and shape over the culture period. Their thickness
      increased substantially over time, and no shrinkage was observed. All specimens
      developed a hyalin-like extracellular matrix containing glycosaminoglycans (GAGs)
      and type II collagen, but significant differences were observed among the three
      different groups. In PGA/MSCs and collagen-PGA/MSCs constructs, the cell growth
      phase and the chondrogenic differentiation phase of MSCs occurred during the
      first 3 weeks. In alginate-PGA/MSCs constructs, cells remained round in the
      hydrogel and cartilage extracellular matrix deposition was delayed. However, at 6
      weeks, alginate-PGA/MSCs constructs exhibited higher contents of GAGs and lower
      contents of type I collagen. These results suggest that the implied time for the
      transplantation of in vitro engineered constructs depends, among other factors,
      on the nature of the scaffold envisioned. In this study, we demonstrated that the
      use of a composite hydrogel-PGA scaffold supported the in vitro growth of
      implantable cartilaginous structures cultured in a bioreactor system.

PMID- 17518584
TI  - Effect of passage and topography on gene expression of temporomandibular joint
      disc cells.
AB  - The temporomandibular joint (TMJ) disc is maintained by a population of
      fibrochondrocytes. Although articular chondrocytes exhibit zonal differences and
      de-differentiate in monolayer culture, such variations are unknown for
      fibrochondrocytic populations. This study's objective was to define topographical
      cellular variations in the porcine TMJ disc and investigate changes in the disc's
      gene expression levels over multiple passages using quantitative reverse
      transcriptase polymerase chain reaction. For topographical characterization,
      samples were acquired from posterior, anterior, lateral, medial, and intermediate
      zone sections and subdivided into inferior and superior halves. For passage
      characterization, cells were plated and passaged for 35 days, with samples
      acquired at every passage. The medial region had the lowest expression of genes
      indicative of fibroblastic activity, but in general, topographical variations
      were limited. Passage effects were evident; gene expression levels of aggrecan,
      collagen type I, and collagen type II dropped 20%, 23%, and 73% per passage,
      respectively. In contrast, decorin and glyseraldehyde-3-phosphate dehydrogenase
      gene expression increased 33% and 27% per passage, respectively. These data
      indicate that TMJ disc cells undergo significant changes due to monolayer
      expansion, experiencing losses in major chondrocytic markers (aggrecan and
      collagen type II) and fibroblastic markers (collagen type I) and posing a serious
      impediment to studies in which cell passaging is required.

PMID- 17518585
TI  - Comparison of immunological properties of bone marrow stromal cells and adipose
      tissue-derived stem cells before and after osteogenic differentiation in vitro.
AB  - Mesenchymal stem cells (MSCs) can be isolated from various tissues and represent
      an attractive cell population for tissue-engineering purposes. MSCs from bone
      marrow (bone marrow stromal cells [BMSCs]) are negative for immunologically
      relevant surface markers and inhibit proliferation of allogenic T cells in vitro.
      Therefore, BMSCs are said to be available for allogenic cell therapy. Although
      the immunological characteristics of BMSCs have been the subject of various
      investigations, those of stem cells isolated from adipose tissue (ASCs) have not
      been adequately described. In addition, the influence of osteogenic
      differentiation in vitro on the immunological characteristics of BMSCs and ASCs
      is the subject of this article. Before and after osteogenic induction, the
      influence of BMSCs and ASCs on the proliferative behavior of resting and
      activated allogenic peripheral blood mononuclear cells (PBMCs) was studied as a
      measure of the immune response (mixed lymphocyte culture). At the same points,
      the expression of immunologically relevant surface markers (e.g., major
      histocompatibility complex (MHC)-I, MHC-II, CD40, CD40L) was measured, and
      correlations between the different sets of results were sought. The pattern of
      surface antigen expression of BMSCs is the same as that of ASCs. Analogous to
      BMSCs, undifferentiated cells isolated from adipose tissue lack expression of MHC
      II; this is not lost in the course of the osteogenic differentiation process. In
      co-culture with allogenic PBMCs, both cell types fail to lead to any significant
      stimulation, and they both retain these characteristics during the
      differentiation process. BMSCs and ASCs suppress proliferation on activated PBMCs
      before and after osteogenic differentiation. Our results confirm that MSCs are
      immune modulating cells. These properties are retained even after osteogenic
      induction in vitro and seem to be similar in BMSCs and ASCs. Our results suggest
      that allogenic transplantation of BMSCs and ASCs would be possible, for example,
      in the context of tissue engineering.

PMID- 17518586
TI  - Survival of cultured allogeneic limbal epithelial cells following corneal repair.
AB  - In this study a technique for determining donor cell fate following corneal
      grafting was evaluated. Patients treated for limbal deficiency with allogeneic
      cultured corneal epithelial cells were studied to determine the fate of the
      grafted cells. The technique was evaluated initially through the use of donor
      eyes and then applied to the clinical analysis of 7 patients who had received a
      cultured corneal epithelial allograft. Cells removed from the cornea and any
      retrieved tissue were analyzed via polymerase chain reaction (PCR) genotyping to
      determine the origin of the cells populating the patients' healed cornea. A
      mixture of genotypes was detected in a cornea retrieved from a patient following
      a fully penetrating keratoplasty who had received a mixture of allogeneic tissue.
      Donor cells were no longer detected on the corneal surface of all 7 cases beyond
      28 weeks postgraft. At these later time points, only patient genotype could be
      detected. These results demonstrate that PCR genotyping can be used to determine
      the origin of cells populating the surface of the cornea following the grafting
      of cultured allogeneic cells and demonstrates that transplanted cultured limbal
      epithelial cells do not persist on the surface of the host cornea for more than
      28 weeks.

PMID- 17518587
TI  - Bespoke human hypertrophic chondrocytic cell lines provide the osteoinductive
      signals required for vascularized bone formation.
AB  - Hypertrophic cartilage provides the morphological and biochemical template for
      orchestrating bone growth. To produce a bone-inductive material such as
      hypertrophic cartilage for clinical use, we have conditionally immortalized
      hypertrophic chondrocytic cells from human femur and expanded them in vitro
      through more than 145 divisions. The clonal cell lines generated by this process
      consistently express signals that induce both rat and human marrow cells to
      differentiate in vitro into osteoblastic cells. Further, implantation of the cell
      free extracellular matrix from the immortalized chondrocytic cells causes
      vascularized bone to form in vivo in bony defects, but not in ectopic sites such
      as skeletal muscle. This study shows that molecular techniques can be used to
      generate bespoke human cell lines for bone tissue engineering. It also
      demonstrates that matrix material generated from human immortalized hypertrophic
      chondrocytic cells may provide an abundant, efficacious, and safer alternative to
      bone autograft--the currently preferred material for fracture repair.

PMID- 17518588
TI  - Intervertebral disc regeneration using platelet-rich plasma and biodegradable
      gelatin hydrogel microspheres.
AB  - This study evaluated the regenerative effects of platelet-rich plasma (PRP) for
      the degenerated intervertebral disc (IVD) in vivo. After induction of IVD
      degeneration in rabbits, we prepared PRP by centrifuging blood obtained from
      these rabbits. These PRP were injected into the nucleus pulposus (NP) of the
      degenerated IVDs after impregnation into gelatin hydrogel microspheres that can
      immobilize PRP growth factors physiochemically and release them in a sustained
      manner with the degradation of the microspheres. As controls, microspheres
      impregnated with phosphate-buffered saline (PBS) and PRP without microspheres
      were similarly injected. Histologically, notable progress in IVD degeneration
      with time courses was observed in the PBS control, PRP-only, and sham groups. In
      contrast, progress was remarkably suppressed over the 8-week period in the PRP
      group. Moreover, in immunohistochemistry, intense immunostaining for proteoglycan
      in the NP and inner layer of the annulus fibrosus was observed 8 weeks after
      administration of PRP-impregnated microspheres. Almost all microspheres were
      indistinct 8 weeks after the injection, and there were no apparent side effects
      in this study. Our results suggest that the combined administration of PRP and
      gelatin hydrogel microspheres into the IVD may be a promising therapeutic
      modality for IVD degeneration.

PMID- 17518589
TI  - Identification of differentially expressed genes in hepatocyte/endothelial cell
      co-culture system.
AB  - Cell-cell communication between multiple-cell populations is believed to be
      important for the activation of many cellular functions. Previously, we showed
      that, in the rat hepatoma cell line Fao, grown in a layered co-culture system
      with a human umbilical vein endothelial cell (HUVEC) sheet, the expression of
      albumin and apolipoprotein A-I increased time-dependently for 10 days and was
      maintained at a significantly higher level than Fao without the HUVEC sheet.
      Because the gene-expression profile of hepatocytes and HUVECs under double
      layered co-culture has not previously been elucidated, in the present study, we
      examined the difference in messenger ribonucleic acid expression between Fao or
      HUVEC monolayer cells and double-layered co-cultured Fao cells/HUVECs using
      suppression subtractive hybridization. More than 200 transcripts were
      differentially screened to ensure unique expression. The expression levels of
      genes in the co-cultured and monolayer cells were determined using SYBR Green I
      real-time reverse transcription polymerase chain reaction with species-specific
      primers. We found 23 genes that showed at least a 2-fold difference in expression
      level. Five hepatocyte-specific genes--alpha1-acidglycoprotein, alpha2
      microglobulin, hepcidin, transferrin, and transthyretin--were identified from the
      Fao cells. Two cell-surface protein genes--bone morphogenetic protein receptor
      type II and CD82--which may be related to cell-cell communication, showed greater
      expression in the HUVECs co-cultured with Fao cells. These results indicate that
      many hepatocyte and endothelial cell functions increase in intensity upon layered
      co-culture.

PMID- 17518590
TI  - Formation of biphasic constructs containing cartilage with a calcified zone
      interface.
AB  - The zone of calcified cartilage is the mineralized region of articular cartilage
      that anchors the hyaline cartilage to the subchondral bone and serves to disperse
      mechanical forces across this interface. In an attempt to mimic this zonal
      organization, we have developed the methodology to form biphasic constructs
      composed of cartilaginous tissue anchored to the top surface of a bone substitute
      (porous calcium polyphosphate, CPP) with a calcified interface. To accomplish
      this, chondrocytes were selectively isolated from the deep zone of bovine
      articular cartilage, placed on top of the CPP substrate, and grown in the
      presence of beta-glycerophosphate (10 mM, beta-GP). By 8 weeks, cartilage tissue
      had formed with two zones: a calcified region adjacent to the CPP substrate and a
      hyaline-like zone above. Little or no mineralization occurred in the absence of
      beta-GP. The mineral that formed in vitro was identified as hydroxyapatite,
      similar in composition and crystal size to that found in vivo. The tissue
      stiffness was seven times greater, and the interfacial shear properties at the
      cartilage-CPP interface were at least two times greater in the presence of this
      mineralized zone within the in vitro-formed cartilage than in tissue lacking a
      mineral zone. In conclusion, developing a biphasic construct with a calcified
      zone at the tissue-biomaterial interface resulted in significantly better
      cartilage load-bearing (compressive) properties and interfacial shear strength,
      emphasizing the importance of the presence of a mineralized zone in bioengineered
      cartilage. Because failure due to shear occurred at the cartilage-CPP interface
      instead of the tidemark, as occurs with osteochondral tissue, further study is
      required to optimize this system so that it more closely mimics the native
      tissue.

PMID- 17518591
TI  - Monocytic U937 adhesion, tumor necrosis factor-alpha and interleukin-1 beta
      expression in response to gelatin-based networks grafted with arginine-glycine
      aspartic acid and proline-histidine-serine-arginine-asparagine oligopeptides.
AB  - In this study we synthesized gelatin-based, tissue-engineering, interpenetrating
      network (IPN) scaffolds immobilized with fibronectin (FN)-derived peptides to
      assess monocyte-biomaterial interaction. Human promonocytic U937 cells were
      seeded onto peptide-grafted IPN or tissue-culture polystyrene plate (TCPS) pre
      adsorbed with FN or FN-derived peptides. The presence of RGD influenced U937
      density on IPN. Interleukin-1 beta (IL-1beta) messenger ribonucleic acid (mRNA)
      expression in adherent U937 on treated TCPS was slightly upregulated at 4 h.
      Tumor necrosis factor alpha (TNF-alpha) and IL-1beta mRNA expression in adherent
      U937 on all IPNs was generally downregulated at 4 h. This downregulation of IL
      1beta mRNA apparently varied in IPNs grafted with different ligand and was still
      present at 24 h. TNF-alpha and IL-1beta proteins released from U937 on treated
      TCPS were comparable with the control at 24 h, but TNF-alpha and IL-1beta protein
      expression in U937 on IPNs was lower at 24 h than on the TCPS control. The
      results indicate that the tissue-engineering substrate and the bioactive peptides
      modulate the initial U937 adhesion and the subsequent inflammatory cytokine gene
      and protein expression.

PMID- 17518592
TI  - Continuously microscopically observed and process-controlled cell culture within
      the SlideReactor: proof of a new concept for cell characterization.
AB  - Certain cell types, especially primary human cells, favor a well-defined culture
      environment offering continuous supply of nutrients and oxygen and waste product
      removal. Several bioreactors based on special matrices or hollow fibers have been
      developed that provide such conditions. However, characterization of matrix re
      organization or growth of tissue within these systems is possible only after
      culture termination. Evaluation of the influence of certain medium additives or
      culture conditions (e.g., temperature, oxygenation) on cell viability, expansion,
      and differentiation within these systems remains a challenging task. The
      SlideReactor, a miniaturized hollow fiber-based bioreactor, was developed to
      enable the observation of cells during culture. An operation concept offering
      predefined conditions for various cell types has been designed. For proof of
      concept, primary human cells (hepatocytes, fibroblasts, keratinocytes) and cell
      lines (HepG2, HuH7, C3A, WiDr, SkHep1) were cultured and observed. A series of
      experiments (n=40) showed the feasibility of the set-up; determination of process
      parameters and continuous observation is possible. The SlideReactor may serve as
      a simple and cost-efficient tool for cell characterization and optimization of
      cell-culture conditions.

PMID- 17518593
TI  - Perfusion culture improves the maintenance of cultured liver tissue slices.
AB  - Cultured precision-cut liver tissue slices are useful for studying the metabolism
      and toxicity of xenobiotics in liver. They may also be used to investigate the
      behavior of and interaction between different cell types in an intact histo
      architecture. Because cultured liver tissues undergo a loss of function and
      morphology because of their separation from the blood supply, we investigated
      changes in key protein marker expressions in parenchymal and non-parenchymal
      cells, as well as in the extracellular matrix (ECM) at different time points. We
      also compared conventional culture methods such as static and dynamic cultures
      with perfusion culture, which allows a continuous exchange of the culture medium.
      In conventional culture methods, the expression of vimentin and collagen type IV
      decreased after 5 h in the non-parenchymal cells and the ECM, respectively,
      whereas the hepatocyte nuclear factor 4 alpha (HNF4alpha) staining in the
      hepatocytes remained constant. In perfusion culture, on the other hand, vimentin,
      collagen type IV, and HNF4alpha staining were clearly detectable after 5 h. The
      histo-architecture obtained from perfusion culture was also more compact than
      those obtained from conventional culture methods. After 24 h, only the perfusion
      cultured sample retained protein marker expression in all components of the liver
      tissue. Our results suggest that, to develop improved culture techniques for
      liver slices, changes at the early time-points should be taken into
      consideration. Our results also show that culture techniques that enable a
      continuous exchange of the culture medium seem to be superior to static or
      dynamic cultures in terms of maintaining the protein expression and the histo
      architecture.

PMID- 17518594
TI  - Mechanical strain regulates endothelial cell patterning in vitro.
AB  - Blood vessels of the vertebrate circulatory system typically exhibit tissue
      specific patterning. However, the cues that guide the development of these
      patterns remain unclear. We investigated the effect of cyclic uniaxial strain on
      vascular endothelial cell dynamics and sprout formation in vitro in two
      dimensional (2D) and three-dimensional (3D) culture systems under the influence
      of growth factors. Cells preferentially aligned and moved in the direction
      perpendicular to the major strain axis in monolayer culture, and mechanical
      strain also regulated the spatial location of cell proliferation in 2D cell
      culture. Cells in 3D cell culture could be induced to form sprouts by exposure to
      appropriate growth factor combinations (vascular endothelial growth factor and
      hepatocyte growth factor), and the strain direction regulated the directionality
      of this process. Moreover, cyclic uniaxial strain inhibited branching of the
      structures formed by endothelial cells and increased their thickness. Taken
      together, these data support the importance of external mechanical stimulation in
      the regulation of endothelial cell migration, proliferation, and differentiation
      into primitive vessels.

PMID- 17518595
TI  - Properties of the human umbilical vein as a living scaffold for a tissue
      engineered vessel graft.
AB  - Umbilical cords are usually discarded after delivery, even though they contain a
      set of functional vessels. We investigated whether the human umbilical vein (HUV)
      is suitable as a storable scaffold for the tissue engineering of small-caliber
      vessel grafts. Isolated HUVs were cryopreserved by freezing or vitrification. The
      reaction of the vessels to vasoactive compounds and the mechanical properties
      were determined in an organ bath. Mitochondrial metabolism, release of
      antithrombotic compounds, and platelet adhesion were measured on the luminal
      vessel surface. Seeding with endothelial cells was tested on denuded HUVs. The
      vessels showed a weak response to norepinephrine but were readily contracted by
      serotonin and by the thromboxane A2 mimetic U46619. Endothelium-dependent
      vasorelaxation was weak, reaching significance only for histamine. However, the
      vessels relaxed to sodium nitroprusside, and to acetylcholine if sandwiched with
      human saphenous vein. Cryopreservation did not change the mechanical properties
      in the relevant tension range. Vasoconstriction to potassium chloride and
      serotonin were reduced after freezing (22.9+/-7.6%, 27.7+/-10.2%) and after
      vitrification (2.6+/-5.8%, 4.3+/-7.1%). The mitochondrial metabolism was also
      attenuated after freezing (57.9+/-25.9%) and after vitrification (21.7+/-6.7%).
      Prostacyclin release was elevated after both cryopreservation procedures (4.0
      fold, 3.9-fold), whereas there was no significant change in the adhesion of
      platelets. Denuded HUVs could readily be seeded with isolated endothelial cells
      before and after freezing. We conclude that HUV is suitable as a storable living
      scaffold with antithrombogenic properties.

PMID- 17518596
TI  - Structural bone allograft combined with genetically engineered mesenchymal stem
      cells as a novel platform for bone tissue engineering.
AB  - The presence of live periosteal progenitor cells on the surface of bone
      autografts confers better healing than devitalized allograft. We have previously
      demonstrated in a murine 4 mm segmental femoral bone-grafting model that live
      periosteum produces robust endochondral and intramembraneous bone formation that
      is essential for effective healing and neovascularization of structural bone
      grafts. To the end of engineering a live pseudo-periosteum that could induce a
      similar response onto devitalized bone allograft, we seeded a mesenchymal stem
      cell line stably transfected with human bone morphogenic protein-2/beta
      galactosidase (C9) onto devitalized bone allografts or onto a membranous small
      intestinal submucosa scaffold that was wrapped around the allograft. Histology
      showed that C9-coated allografts displayed early cartilaginous tissue formation
      at day 7. By 6 and 9 weeks, a new cortical shell was found bridging the segmental
      defect that united the host bones. Biomechanical testing showed that C9-coated
      allografts displayed torsional strength and stiffness equivalent to intact femurs
      at 6 weeks and superior to live isografts at 9 weeks. Volumetric and
      histomorphometric micro-computed tomography analyses demonstrated a 2-fold
      increase in new bone formation around C9-coated allografts, which resulted in a
      substantial increase in polar moment of inertia (pMOI) due to the formation of
      new cortical shell around the allografts. Positive correlations between
      biomechanics and new bone volume and pMOI were found, suggesting that the
      biomechanical function of the grafted femur relates to both morphological
      parameters. C9-coated allograft also exhibited slower resorption of the graft
      cortex at 9 weeks than live isograft. Both new bone formation and the persistent
      allograft likely contributed to the improved biomechanics of C9-coated allograft.
      Taken together, we propose a novel strategy to combine structural bone allograft
      with genetically engineered mesenchymal stem cells as a novel platform for bone
      tissue engineering.

PMID- 17518597
TI  - Effects of gamma-irradiation on physical and biologic properties of crosslinked
      hyaluronan tissue engineering scaffolds.
AB  - Hydrogels containing divinyl sulfone (DVS)-crosslinked hyaluronan (HA) (hylans)
      are potentially useful implant biomaterials because of their non-cytotoxicity and
      -antigenicity. However, to successfully fulfill their intended role in vivo,
      their properties (e.g., mechanics, pore size, surface topography, hydrophilicity,
      swelling) must be modulated to match the demands of the target application. This
      study explored whether controlled irradiation with gamma (gamma) can strengthen
      hylans and modulate their physical and biologic properties, as has previously
      been shown to be possible with other natural and synthetic polymers. Hydrated
      hylans containing two different amounts of DVS were irradiated in vacuum to
      increasing doses of gamma (0-13.5 kGy). The properties of the irradiated gels
      were compared with those of non-irradiated controls. Changes to bulk structure
      were evaluated using swelling tests, surface topography and pore structure were
      evaluated using scanning electron microscopy, mechanics were evaluated using
      unconfined compression tests, and surface hydrophilicity was evaluated by
      measuring contact angle changes. Irradiated gels exhibited lower swelling
      capacity, structural weakening, increase in elasticity, surface texturing,
      increased pore size, and decreased surface hydrophilicity in direct correlation
      with received dose. Cells adhered and proliferated readily on the irradiated gel
      surfaces but not on control gels. The irradiated gels, however, deteriorated
      during long-term (<60 days) storage. Irradiation of hylans in a lyophilized state
      instead resulted in gels that were more compact, swelled less, and exhibited
      smaller pores than their hydrated counterparts. The results show that gamma
      irradiation, although useful to modulate hylan gel properties, presents
      challenges of degradation that may be associated with its generation of free
      radicals, HA chain fragmentation, and disruption of DVS crosslinks, particularly
      when the gels are irradiated in their native hydrated state (>98% water content).
      Future studies will optimize parameters for gamma-mediated modulation of hylan
      properties through irradiation under water-free conditions.

PMID- 17518598
TI  - Interconnected network of ganglion-like neural cell spheres formed on hydrozoan
      skeleton.
AB  - Identifying scaffolds supporting in vitro reconstruction of active neuronal
      tissues in their 3-dimensional (3D) conformation is a major challenge in tissue
      engineering. We have previously shown that aragonite coral exoskeletons support
      the development of neuronal tissue from hippocampal neurons and astrocytes. Here
      we show for the first time that the porous aragonite skeleton obtained from bio
      fabricated hydrozoan Millepora dichotoma supports the spontaneous organization of
      dissociated hippocampal cells into highly interconnected 3D ganglion-like tissue
      formations. The ganglion-like cell spheres expanded hundreds of microns across
      and included hundreds to thousands of astrocytes and mature neurons, most of them
      having only cell-cell and no cell-surface interactions. The spheres were linked
      to the surface directly or through a neck of cells and were interconnected
      through thick bundles of dendrites, varicosity-bearing axons, and astrocytic
      processes. Thus, M. dichotoma exoskeleton is a novel scaffold with the
      unprecedented ability to support a highly ordered organization of neuronal
      tissue. This unexpected organization opens new opportunities for neuronal tissue
      regeneration, because the spheres resemble in vivo nervous tissue having high
      volume of cells associated primarily through cell-cell rather than cell-matrix
      interactions.

PMID- 17518599
TI  - Transplantation of allogeneic chondrocytes cultured in fibroin sponge and
      stirring chamber to promote cartilage regeneration.
AB  - Cartilage regeneration using a fibroin sponge and a stirring chamber was
      investigated to improve the potential of articular cartilage tissue engineering.
      Chondrocytes seeded on the fibroin-sponge scaffolds were cultured in the stirring
      chamber (a bioreactor facilitating mechanical stimulation) for up to 3 weeks.
      Changes in DNA content, glycosaminoglycan (GAG) amount, integrin subunits alpha5
      and beta1 fluorescence intensity, and morphologic appearance, were studied to
      evaluate tissue maturity. Seeded scaffolds subjected to the stirring chamber
      demonstrated significant increases in both DNA content (38.9%) and GAG content
      (54.3%) at day 21 compared to the control group. In addition, the stirring
      chamber system facilitated a maturation of cartilage tissue showed by histologic
      examination, after a staining of proteoglycan and type II collagen. Clinical
      feasibility of the fibroin and stirring chamber system was evaluated using rabbit
      models with cartilage defect. Large defects on rabbit knee joints were repaired
      with regenerated cartilage, which resembles hyaline cartilage at 12 weeks after
      operation. These studies demonstrated the potential of such mechanically
      stimulated scaffold/cell constructs to support chondrogenesis in vivo.

PMID- 17518600
TI  - Transplantation of preserved human amniotic membrane for bladder augmentation in
      rats.
AB  - Although gastrointestinal segments have been widely used for bladder
      reconstruction, they are not ideal because of the possible complications.
      Searches have therefore continued for an alternative material for augmentation.
      Here, we performed bladder augmentation in rats using human amniotic membrane
      (hAM). Morphologically, the hAM-augmented bladder revealed regeneration of
      urothelium, detrusor smooth muscle, and nerve fibers within 3 months post
      operatively. In our functional evaluation of bladder strips, we compared hAM
      augmented bladders with bladders augmented using small intestinal submucosa
      (SIS). For example, at 6 months post-operatively, contractions of the following
      size (as a percentage of the responses in the control-bladder group) were
      obtained in response to high potassium, carbachol, and electrical field
      stimulation, respectively: hAM 22% vs SIS 15%, hAM 15% vs SIS 7%, hAM 5.3% vs SIS
      1.3% (no significant differences, hAM vs SIS). Both hAM- and SIS-augmented
      bladders displayed adequate capacity and compliance. The present results indicate
      that, for bladder augmentation, hAM can be used as a scaffold and is comparable
      in this respect with SIS. hAM can be more easily obtained than SIS and requires
      little preparation, and its use raises few ethical questions. Hence, hAM may
      represent a new therapeutic alternative for urological reconstructions.

PMID- 17518601
TI  - Endothelial progenitor and mesenchymal stem cell-derived cells persist in tissue
      engineered patch in vivo: application of green and red fluorescent protein
      expressing retroviral vector.
AB  - An unresolved question regarding tissue-engineered (TE) cardiac valves and
      vessels is the fate of the transplanted cells in vivo. We have developed a
      strategy to track the anatomic location of seeded cells within TE constructs and
      neighboring tissues using a retroviral vector system encoding green and red
      fluorescent proteins (GFPs and RFPs, respectively) in ovine circulating
      endothelial progenitor cells (EPCs) and bone marrow-derived mesenchymal stem
      cells (BMSCs). We demonstrate that stable transduction ex vivo with high-titer
      Moloney murine leukemia virus-based retroviral vector yields transduction
      efficiency of greater than 97% GFP(+) EPC- and RFP(+) mesenchymal stem cell (MSC)
      derived cells. Cellular phenotype and transgene expression were also maintained
      through 25 subsequent passages. Using a retroviral vector system to distinguish
      our pre-seeded cells from tissue-resident progenitor cells and circulating
      endothelial and marrow-derived precursors, we simultaneously co-seeded 2 x 10(6)
      GFP(+) EPCs and 2 x 10(5) RFP(+) MSCs onto the TE patches. In a series of ovine
      pulmonary artery patch augmentation studies, transplanted GFP(+) EPC- and RFP(+)
      MSC-derived cells persisted within the TE patch 7 to 14 days after implantation,
      as identified using immunofluorescence. Analysis showed 81% luminal coverage of
      the TE patches before implantation with transduced cells, increasing to 96% at
      day 7 and decreasing to 67% at day 14 post-implantation. This suggests a temporal
      association between retroviral expression of progenitor cells and mediating
      effects of these cells on the physiological remodeling and maturation of the TE
      constructs. To our knowledge, this is the first cardiovascular tissue-engineering
      in vivo study using a double-labeling method to demonstrate a direct evidence of
      the source, persistence, and incorporation into a TE vascular patch of co
      cultured and simultaneously pre-seeded adult progenitor cells.

PMID- 17518602
TI  - A biodegradable, acellular xenogeneic scaffold for regeneration of the vocal fold
      lamina propria.
AB  - A novel method for preparing an acellular xenogeneic extracellular matrix
      scaffold for tissue engineering was developed. Bovine vocal fold lamina propria
      specimens were treated with high-concentration sodium chloride, nucleic acid
      digestion, and ethanol dehydration for decellularization and removal of
      immunogenic foreign epitopes. Human vocal fold fibroblasts from primary culture
      were seeded onto the acellular scaffolds and cultured for 21 days. The
      decellularized and the recellularized scaffolds were examined by light
      microscopy, fluorescent microscopy, and scanning electron microscopy. Collagen
      synthesis and release by fibroblasts were quantified by the Sircol assay, whereas
      the synthesis and release of hyaluronic acid, decorin, and fibronectin were
      assessed by enzyme-linked immunosorbent assays. Viscoelastic shear properties of
      the scaffolds were quantified by a simple-shear rheometer at frequencies of up to
      250 Hz. Preliminary results showed that a biodegradable, acellular extracellular
      matrix scaffold with an intact basement membrane and 3-dimensional structure of
      the matrix proteins was engineered. Vocal fold fibroblasts readily attached to
      and infiltrated the scaffold with high viability and active protein synthesis,
      demonstrating the biocompatibility. The elastic shear modulus and dynamic
      viscosity of the acellular scaffold and the fibroblast-repopulated scaffold were
      comparable to those of the human vocal fold cover. These findings support the
      potential of the scaffold as a xenograft for vocal fold reconstruction and
      regeneration.

PMID- 17518603
TI  - Engineered cell-adhesive nanoparticles nucleate extracellular matrix assembly.
AB  - Tissue engineering aims to regenerate new biological tissue for replacing
      diseased or injured tissues. We propose a new approach to accelerate the
      deposition of cell-secreted matrix proteins into extracellular matrix fibrils. We
      examined whether dynamic substrates with nanoscale ligand features allowing for
      alpha5beta1 integrin recruiting, cellular tension generation, and alpha5beta1
      integrin mobility would enhance fibronectin matrix assembly in a ligand model
      system that is routinely not sufficient for its induction. To this end, we
      developed biodynamic substrates consisting of cell adhesive fragment from the 9th
      and 10th type repeats of fibronectin (FNf ) functionalized to 100 nm
      prefabricated albumin nanoparticles (ANPs). FNf-ANPs modulated cellular spreading
      processes, promoting the development of stellate or dendritic morphologies.
      Concomitant with the spreading, FNf-ANPs rapidly recruited beta1 integrins to
      focal contacts and promoted the migration of beta1 integrins centripetally from
      the cell periphery toward the center. FNf-ANPs stimulated the deposition of
      secreted fibronectin into matrix fibrils; FNf, the key ligand alone, was not
      sufficient for fibronectin fibrillogenesis. When FNf-ANPs were displayed from
      "immobilized" substrates, abolishing any mobility of ligated beta1 integrins,
      fibronectin matrix assembly was abrogated, implicating the role of dynamic matrix
      display on matrix assembly. Receptor ligation of FNf-ANPs via noncontractile
      adhesions was not sufficient to stimulate fibrillogenesis, and Rho-kinase
      inhibitors abolished fibronectin matrix deposition. Our approach highlights the
      possibility of engineering integrin-based extracellular matrix assembly using
      nanotechnology, which may have implications for improved biomaterials for wound
      repair and basic understanding of matrix remodeling within pathogenesis and
      biomedicine.

PMID- 17518604
TI  - Role of fiber diameter in adhesion and proliferation of NIH 3T3 fibroblast on
      electrospun polycaprolactone scaffolds.
AB  - The goal of the current study was to find the quantitative relationship between
      electrospun polycaprolactone scaffold fiber diameter and NIH 3T3 fibroblast
      adhesion and growth kinetics. By varying 3 important process parameters--solution
      concentration, voltage, and collector screen distance--different average fiber
      diameters ranging from 117 to 1,647 nm were obtained. Although 117 nm represented
      the lowest possible fiber diameter obtainable, these fibers had beads in them. An
      increase in fiber diameter to 428 nm led to uniform fibers without any beads.
      Fiber distribution pattern was a single mode for all the scaffolds except at the
      largest-diameter end. The diameter distribution changed from single to bimodal at
      1,647 nm, suggesting some instability in the process. It was found that cell
      adhesion and growth kinetics are significantly affected as a function of fiber
      diameter. Beaded scaffolds offered the lowest cell adhesion and minimal growth
      kinetics despite having the lowest average fiber diameter. When uniform fibers
      were formed and the average fiber was in the nanofiber range (428-1051 nm), cell
      adhesion and growth kinetics decreased as a function of increasing fiber
      diameter. Cell adhesion kinetics remained invariant when the average fiber
      diameter was in the micron range (1,647 nm), whereas cell-growth kinetics were
      slightly greater than with 900 nm scaffolds. We propose that the uniformness of
      fibers and the average fiber diameter may play an important role in modulating
      cellular attachment and proliferation in electrospun tissue engineering
      scaffolds.

PMID- 17518605
TI  - Islet encapsulation: strategies to enhance islet cell functions.
AB  - Diabetes is one of the most prevalent, costly, and debilitating diseases in the
      world. Although traditional insulin therapy has alleviated the short-term
      effects, long-term complications are ubiquitous and harmful. For these reasons,
      alternative treatment options are being developed. This review investigates one
      appealing area: cell replacement using encapsulated islets. Encapsulation
      materials, encapsulation methods, and cell sources are presented and discussed.
      In addition, the major factors that currently limit cell viability and
      functionality are reviewed, and strategies to overcome these limitations are
      examined. This review is designed to introduce the reader to cell replacement
      therapy and cell and tissue encapsulation, especially as it applies to diabetes.

PMID- 17518606
TI  - Epidermal growth factor signaling for matrix-dependent cell proliferation and
      differentiation in primary cultured hepatocytes.
AB  - Understanding hepatocellular signaling occurring in biomaterial systems is
      important for successful hepatic tissue engineering. Toward this end, we employed
      synthetic glycopolymers, as artificial matrices, to examine integrin-mediated
      epidermal growth factor (EGF) signaling in primary hepatocyte cultures. We
      dispersed hepatocytes on a collagen matrix or on a synthetic glycopolymer matrix
      and subsequently stimulated them with EGF. Only hepatocytes cultured on collagen
      proliferated, and we observed significant expression of cyclin B1 in these cells.
      Pharmacological agents, LY294004 (a phosphatidylinositol [PI] 3-kinase inhibitor)
      and AG1478 (an EGF kinase receptor inhibitor), blocked hepatocyte proliferation
      and cyclin B1 expression. In addition, EGF-stimulated hepatocytes formed
      spheroids, exhibited membrane ruffling, and increased tryptophan 2,3-oxygenase
      (TO) expression when cultured on glycopolymer matrices. Interestingly, PI 3
      kinase inhibition suppressed membrane ruffling, spheroid formation, and TO
      expression. Taken together, this data suggests PI 3-kinase plays an important
      role in mediating cross talk between integrin and the EGF signaling pathways in
      primary hepatocyte cultures.

PMID- 17518607
TI  - Intermittent applications of continuous ultrasound on the viability,
      proliferation, morphology, and matrix production of chondrocytes in 3D matrices.
AB  - Chondrocytes, the cellular component of the articular cartilage, have long been
      recognized as strain-sensitive cells, and have the ability to sense mechanical
      stimulation through surface receptors and intracellular signaling pathways. This
      strain-induced biological response of chondrocytes has been exploited to
      facilitate chondrocyte culture in in vitro systems; examples include the
      application of hydrostatic pressure, dynamic compression, hydrodynamic shear
      (i.e., rotating bioreactors), and low-intensity pulsed ultrasound (US). While the
      ability of US to influence chondrogenesis has been documented, the precise
      mechanisms of US-induced stimulation continue to be investigated. There remains a
      critical need to evaluate the impact of US on chondrocytes in 3D culture, which
      is a necessary microenvironment for maintaining the chondrocyte phenotype. In
      this study, a continuous US wave for predetermined time intervals was employed,
      as opposed to pulsed US used in previous studies, to stimulate chondrocytes
      seeded in 3D scaffolds. The chondrocytes (n = 6) were subjected to US stimulation
      as follows: 1.5 MHz for 161 seconds, 5.0 MHz for 51 seconds, and 8.5 MHz for 24
      seconds, and the US signal was applied twice in a 24-hour period. Scaffolds that
      are not stimulated by US served as the control. Both the control and the US
      stimulated groups were maintained in culture for 10 days, and at the conclusion
      of the culture period, chondrocytes were assayed for total DNA content,
      morphology, and cartilage-specific gene expression by reverse transcriptase
      polymerase chain reaction. Our results show that chondrocytes when stimulated
      with continuous US for predetermined time intervals possessed higher cellular
      viability (1.2 to 1.4 times) and higher levels of type II collagen and aggrecan
      mRNA expression when compared to controls.

PMID- 17518608
TI  - In vivo osteogenic potential of human adipose-derived stem cells/poly lactide-co
      glycolic acid constructs for bone regeneration in a rat critical-sized calvarial
      defect model.
AB  - Recent studies suggest that human adipose tissue contains pluripotent stem cells,
      which are similar to bone marrow-derived stem cells. The objective of the present
      study was to assess the effect in bone regenerating capability of human adipose
      derived stem cells (ADSCs) cultured in osteogenic media layered over poly lactide
      co-glycolic acid (PLGA) and implanted in a critical nude rat calvarial defect.
      Twenty-seven nude rats were randomized into 3 groups (n = 9): 1) PLGA alone
      (control), 2) PLGA with undifferentiated ADSCs, and 3) PLGA with differentiated
      ADSCs. These 3 groups were divided into 9 subgroups (n = 3) according to in vitro
      pre-cultured periods (day 1 pre-culture (Group1), day 7 pre-culture (Group2), and
      day 14 pre-culture (Group3)) before implantation. An 8 mm critical-size circular
      calvarial defect was made in each nude rat. Specimens were harvested at 12 weeks
      post-implantation and evaluated radiographically and histologically.
      Radiodensitometric analysis revealed significantly higher bone growth in implants
      pre-cultured in osteogenic media for 14 days for Group 3. Histomorphometric
      analysis demonstrated that Groups 2 and 3 had bone formation filling 35% to 72%
      of the area of the defect after transplantation with cells that had been pre
      cultured for 14 days. Constructs with differentiated ADSCs (Group 3) had
      noticeably more maximal and robust bone tissue regeneration than constructs with
      undifferentiated ADSCs (Group 2). These data provide evidence that constructs or
      implants made of PLGA and osteogenically differentiated ADSCs pre-cultured for 14
      days before transplantation have better, more-robust bone regeneration capability
      in critical-sized skeletal defects than constructs with undifferentiated ADSCs.
      Human adipose derived stem cells can therefore be used as seed cells to construct
      tissue-engineered bone.

PMID- 17518609
TI  - Cyclic straining of cell-seeded synthetic ligament scaffolds: development of
      apparatus and methodology.
AB  - Cyclic tensile strains acting along a ligament implant are known to stimulate
      cells that colonize it to proliferate and to synthesize an extracellular matrix
      (ECM), which will then remodel and form a new ligament structure. However, this
      process of tissue induction is poorly understood. As a first step toward
      elucidating this process, we aimed to investigate the effect of cyclic tensile
      strain on the proliferation of, and possible ECM synthesis by, cells colonizing
      ligament scaffolds. Because there was no commercially available apparatus to
      undertake such investigation the objectives of this study were to develop an
      apparatus for the application of cyclic tensile strains on cell-seeded synthetic
      ligament scaffolds and to develop and validate (through preliminary data obtained
      using the apparatus) methodology for studying the effect of cyclic strain on cell
      proliferation. We designed a multi-station test apparatus that operated inside an
      incubator. It allowed the application of tensile cyclic strains of between 0.5%
      and 5% at a frequency of 1 Hz on cell-seeded polyester ligament scaffolds
      immersed in culture medium. Test stations with windows in their bases could be
      easily de-coupled from the apparatus. This allowed monitoring of cell
      proliferation and morphology, with inverted light microscopy, through the
      transparent glass bases of the culture wells. Preliminary experiments lasting for
      1 day or 9 weeks examined the effect of selected aspects of the cyclic strain on
      proliferation of cells seeded onto ligament scaffolds. Tests lasting for 1 day
      showed that the application of cyclic tensile strain of 5% for 4 h increased cell
      proliferation 24% above that observed in unstrained controls (p < .05). Scanning
      electron microscopy data from tests lasting for 9 weeks demonstrated further the
      dependency of cell proliferation and possible ECM synthesis on the magnitude of
      the strain. The larger the amplitude, the greater was the coverage of the
      scaffold with cells and ECM. Transmission electron microscopy of the ECM observed
      at 9 weeks showed evidence of collagen fibrils aligned in the direction of load
      in strained scaffolds, whereas the tissue on the control scaffolds was random.

PMID- 17518611
TI  - Gene Therapy Clinical Studies And The CONSORT Guidelines.

PMID- 17518610
TI  - Chemical dimerization of fibroblast growth factor receptor-1 induces myoblast
      proliferation, increases intracardiac graft size, and reduces ventricular
      dilation in infarcted hearts.
AB  - The ability to control proliferation of grafted cells in the heart and consequent
      graft size could dramatically improve the efficacy of cell therapies for cardiac
      repair. To achieve targeted graft cell proliferation, we created a chimeric
      receptor (F36Vfgfr-1) composed of a modified FK506-binding protein (F36V) fused
      with the cytoplasmic domain of the fibroblast growth factor receptor-1 (FGFR-1).
      We retrovirally transduced mouse C2C12 and MM14 skeletal myoblasts with this
      construct and treated them with AP20187, a dimeric F36V ligand ("dimerizer"), in
      vitro and in vivo to induce receptor dimerization. Dimerizer treatment in vitro
      activated the mitogen-activated protein kinase pathway and induced proliferation
      in myoblasts expressing F36Vfgfr-1 comparable with the effects of basic FGF. Wild
      type myoblasts did not respond to dimerizer. Subcutaneous grafts composed of
      myoblasts expressing F36Vfgfr-1 showed a dose-dependent increase in DNA synthesis
      with dimerizer treatment. When myoblasts expressing F36Vfgfr-1 were injected into
      infarcted hearts of nude mice, dimerizer treatment resulted in a dose-dependent
      increase in graft size, from 20 +/- 3 to 42.9 +/- 4.3% of the left ventricle.
      Blinded echocardiographic analysis demonstrated that larger graft size was
      associated with a dose-dependent reduction in ventricular dilation after
      myocardial infarction, although animals with the largest grafts showed an
      increased incidence of ventricular tachycardia. Thus, selective proliferation of
      genetically modified graft cells can be induced with a systemically administered
      synthetic molecule in vitro or in vivo. Control of intramyocardial graft size by
      this approach may allow optimization of cell-based therapy to obtain desired
      cardiac function postinfarction.

PMID- 17518612
TI  - Local and distant immune-mediated control of colon cancer growth with fusogenic
      membrane glycoproteins in combination with viral oncolysis.
AB  - We evaluated whether the expression of measles virus fusogenic membrane
      glycoproteins H and F (MV-FMG), encoded by a herpes simplex virus type 1 (HSV-1)
      amplicon vector, can serve with or without viral oncolysis (G47Delta) and
      facultative irinotecan chemotherapy, alone or in combination with the monoclonal
      epidermal growth factor receptor (EGFR) inhibitory antibody cetuximab, as a
      platform for inducing tumor-specific immune responses against colon cancer. We
      demonstrated in vitro that MV-FMG expression in murine cells resulted in cell
      cell fusion and synergistically enhanced the cytotoxicity of irinotecan alone or
      in combination with cetuximab. In a bilateral syngeneic subcutaneous MC38 and
      Colon26 tumor model in C57BL/6 and BALB/c mice we assessed both the effect on
      directly vector-treated tumors and the effect on contralateral, not directly
      vector-treated tumors. We demonstrated that the combination of three treatment
      components with or without cetuximab resulted in the best volume reduction of
      both directly vector-treated and not directly vector-treated tumors as well as
      pronounced infiltration of both tumor types with natural killer cells,
      macrophages, and T cells. T cells of these animals exhibited strong ex vivo
      cytotoxic activity against the tumor cells, indicating that the antineoplastic
      effect on untreated tumors was mediated by an antitumor immune response.
      Preexisting immunity against HSV-1 or measles virus had no detrimental effect on
      overall treatment efficacy. Our data indicate that MV-FMG expression in
      combination with viral oncolysis with or without clinically relevant chemotherapy
      for colon cancer treatment warrants further investigation.

PMID- 17518613
TI  - Modification of the Rb-binding domain of replication-competent adenoviral vector
      enhances cytotoxicity against human esophageal cancers via NF-kappaB activity.
AB  - A replication-competent adenoviral vector deficient for expression of the early
      E1B55K protein has been applied in clinical studies. The vector, however, was not
      fully effective for the treatment of human cancer. In this study, the E1A gene
      (which encodes an Rb-binding domain protein) of the adenoviral vector AxE1AdB was
      further engineered with a point mutation designed to abolish binding to Rb
      protein (pRb) and arrest the cell cycle (AxdAdB-3). The difference in the
      cytotoxicity of these vectors in two cancer cell lines was observed in
      association with differences in replication, infection efficiency, and expression
      levels of adenovirus receptors. Relative to the parent vector (AxE1AdB), which
      worked in a manner similar to ONYX-015, AxdAdB-3 with the mutated pRb-binding
      motif demonstrated increased cytotoxicity against p53-mutant human esophageal
      cancer cell lines EC-GI-10 and T.Tn. AxdAdB-3 showed a greater oncolytic effect
      than AxE1AdB in vivo despite almost the same replication efficiency in vitro.
      Unexpectedly, cell cycle arrest in AxdAdB-3-infected cells was less efficient
      than that in cell lines infected with AxE1AdB. However, AxdAdB-3 strongly reduced
      NF-kappaB activity and thereby enhanced apoptosis more than AxE1AdB did. These
      data demonstrate that the Rb-binding domain of E1A can regulate NF-kappaB
      activity and that modifications to this domain may lead to advances in gene
      therapies for the treatment of human cancers.

PMID- 17518614
TI  - Human immunodeficiency viral vector pseudotyped with the spike envelope of severe
      acute respiratory syndrome coronavirus transduces human airway epithelial cells
      and dendritic cells.
AB  - The human severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly
      infectious virus that causes severe respiratory infections in humans. The spike
      envelope glycoprotein of SARS-CoV, the main determinant of SARS-CoV tropism, was
      isolated and used to pseudotype a human immunodeficiency virus (HIV)-based
      vector. Spike-pseudotyped HIV vector was generated and evaluated in vitro on well
      differentiated human airway epithelial cells and bronchial explants and in vivo
      in murine airways. The spike envelope was less efficient at promoting HIV vector
      transduction of murine airway epithelium than an optimized deletion mutant of the
      Zaire ebolavirus envelope glycoprotein (NTD6L), which was used as a benchmark.
      However, spike-pseudotyped HIV vector was substantially more efficient than NTD6L
      pseudotyped vector on human airway epithelium as demonstrated by lacZ gene
      transfer in primary cultures of epithelial cells and bronchial explants. In
      addition, this study shows that spike-pseudotyped HIV -based vector can
      efficiently transduce human dendritic cells and epithelial cells of the
      esophagus, which may have implications in investigating mechanisms of SARS-CoV
      pathogenesis. Spike-pseudotyped HIV-based vector is a novel lung-directed gene
      transfer vehicle that holds promise for the treatment of genetic lung diseases
      such as cystic fibrosis or alpha(1)-antitrypsin deficiency.

PMID- 17518615
TI  - In vivo culture of encapsulated endostatin-secreting Chinese hamster ovary cells
      for systemic tumor inhibition.
AB  - Microencapsulation of recombinant cells is a novel alternative approach to tumor
      gene therapy. Therapeutic protein delivery can be sustained for systemic
      treatment of tumors because the recombinant cells are enclosed in microcapsules
      and the semipermeable membrane of the microcapsules protects the cells from host
      immune rejection and reduces the need for frequent injection. In this study, we
      describe a method to systemically inhibit tumor growth by in vivo culture of
      antiangiogenic endostatin-secreting Chinese hamster ovary (CHO) cells in
      microcapsules as small as 200 microm in diameter. Peritoneal administration of
      encapsulated endostatin-CHO cells inhibited melanoma growth to 66.4% and enhanced
      the survival of treated mice to 80% by 27 days posttreatment. Continuous systemic
      release of endostatin from microcapsules offers an effective therapeutic strategy
      to eradicate solid tumors.

PMID- 17518616
TI  - Unique integration profiles in a canine model of long-term repopulating cells
      transduced with gammaretrovirus, lentivirus, or foamy virus.
AB  - Recent advances have allowed for improved retrovirus-mediated gene transfer, and
      therapeutic benefits have been described in patients. These successes have shown
      the potential of hematopoietic stem cell (HSC) gene therapy, but treatment
      related leukemia and benign expansion of gene-modified clones have shifted the
      attention toward safety. The delayed onset of adverse events in gene therapy
      clinical trials emphasizes the importance of long-term integration site studies
      in large animal models. We have addressed safety by characterizing the genomic
      location of 555 integration sites of the three most commonly used integrating
      retroviral vectors, that is, gammaretrovirus, lentivirus, and foamy virus, in
      long-term repopulating cells from dogs. Gammaretroviral integrants showed the
      most significant frequency of occurrence very close (<2.5 kb) to transcription
      start sites, but a substantial portion of all three retroviral integrants were
      within 50 kb. Importantly, gammaretroviral integrants were found more frequently
      in and near proto-oncogenes, suggesting this retroviral system may be the most
      prone to adverse gene activation. These data suggest that gammaretroviral vectors
      may have the highest intrinsic risk, but also emphasize that no vector system can
      be defined as "safe" based solely on integration profile.

PMID- 17518617
TI  - Review: ex vivo engineering of living tissues with adult stem cells.
AB  - Adult stem cells have the potential to revolutionize regenerative medicine with
      their unique abilities to self-renew and differentiate into various phenotypes.
      This review examines progress and challenges in ex vivo tissue engineering with
      adult stem cells. These rare cells are harvested from a variety of tissues,
      including bone marrow, adipose, skeletal muscle, and placenta, and differentiate
      into cells of their own lineage and in some cases atypical lineages. Insight into
      the stem cell niche leads to the identification of matrix components, soluble
      factors, and physiological conditions that enhance the ex vivo amplification and
      differentiation of stem cells. Scaffolds composed of metals, naturally occurring
      materials, and synthetic polymers organize stem cells into complex spatial
      groupings that mimic native tissue. Cell signals from covalently bound ligands
      and slowly released regulatory factors in scaffolds direct stem cell fate. Future
      advances in stem cell biology and scaffold design will ultimately improve the
      efficacy of tissue substitutes as implants, in research, and as extracorporeal
      devices.

PMID- 17518618
TI  - Design of a filamentous polymeric scaffold for in vivo guided angiogenesis.
AB  - Angiogenesis is mandatory for reperfusion of viable tissues, and lack of
      vascularization may cause ischemia. The increasing disparity between the demand
      and availability of adequate substitutes for small-diameter human blood vessels
      has prompted an intensive search for artificial materials or biological allograft
      tissues, both of which usually fail in the long term. The objective of this study
      was to pioneer a novel model for in vivo guided angiogenesis based on a specific
      design process of a filamentous polymeric scaffold with endothelial cells in a 3
      dimensional culture system. To our knowledge, this is the first report of an in
      vivo guided angiogenesis approach based on a 2-step model, composed of
      endothelial cells and a filamentous polymeric scaffold framework. Endothelial
      cells that had been cultured on a specifically designed filamentous polymeric
      scaffold within a regulated dynamic tissue culture system were shown in vivo to
      induce guided angiogenesis. Cells seeded on a biodegradable polymeric scaffold
      were implanted into mice. On day 28 after implantation, analysis revealed a
      guided angiogenic process along the path of the implanted polymeric scaffold as
      well as initial evidence for early maturation of engineered vessels, allowing red
      blood cells to flow through the forming lumina of new vessels as the polymer
      degraded. The authors conclude that in vivo guided angiogenesis can be achieved
      by combining endothelial cells with biodegradable filamentous polymeric scaffolds
      and that this model can lay the cornerstone for vascular engineering and future
      development of clinically available protocols aimed to treat life-threatening
      cardiovascular conditions.

PMID- 17518619
TI  - Adipose tissue engineering based on the controlled release of fibroblast growth
      factor-2 in a collagen matrix.
AB  - Adipose tissue forms when basement membrane extract (Matrigel) and fibroblast
      growth factor-2 (FGF-2) are added to our mouse tissue engineering chamber model.
      A mouse tumor extract, Matrigel is unsuitable for human clinical application, and
      finding an alternative to Matrigel is essential. In this study we generated
      adipose tissue in the chamber model without using Matrigel by controlled release
      of FGF-2 in a type I collagen matrix. FGF-2 was impregnated into biodegradable
      gelatin microspheres for its slow release. The chambers were filled with these
      microspheres suspended in 60 microL collagen gel. Injection of collagen
      containing free FGF-2 or collagen containing gelatin microspheres with buffer
      alone served as controls. When chambers were harvested 6 weeks after
      implantation, the volume and weight of the tissue obtained were higher in the
      group that received collagen and FGF-2 impregnated microspheres than in controls.
      Histologic analysis of tissue constructs showed the formation of de novo adipose
      tissue accompanied by angiogenesis. In contrast, control groups did not show
      extensive adipose tissue formation. In conclusion, this study has shown that de
      novo formation of adipose tissue can be achieved through controlled release of
      FGF-2 in collagen type I in the absence of Matrigel.

PMID- 17518620
TI  - Extended-term culture of bone cells in a compartmentalized bioreactor.
AB  - A specialized bioreactor is used to grow mineralizing, collagenous tissue up to
      150 microm thick from an inoculum of isolated murine (mouse calvaria MC3T3-E1,
      American Type Culture Collection (ATCC) CRL-2593) or human (hFOB 1.19 ATCC CRL
      11372) fetal osteoblasts over uninterrupted culture periods longer than 120 days
      (4 months). Proliferation and phenotypic progression of an osteogenic-cell
      monolayer into a tissue consisting of 6 or more cell layers of mature osteoblasts
      in the bioreactor was compared with cell performance in conventional tissue
      culture polystyrene (TCPS) controls. Cells in the bioreactor basically matched
      results obtained in TCPS over a 15-day culture interval, but loss of insoluble
      extracellular matrix and an approximate doubling of apoptosis rates in TCPS after
      30 days indicated that progressive instability of cultures maintained in TCPS
      with periodic refeeding but without subculture. In contrast, stable cultures were
      maintained in the bioreactor for more than 120 days, suggesting that extended
      term tissue maintenance is feasible with little or no special technique.
      Transmission electron microscopy ultramorphology of tissue derived from hFOB 1.19
      recovered from the bioreactor after only 15 days of culture showed evidence of
      osteocytic-like processes and gap junctions between cells like those observed in
      vivo, in addition to elaboration of the usual osteoblastic markers such as
      alkaline phosphatase activity and mineralization (alizarin red). Thus, the
      bioreactor design based on the principle of simultaneous growth and dialysis was
      shown to create an extraordinarily stable peri-cellular environment that better
      simulates the in vivo condition than conventional tissue culture. The bioreactor
      shows promise as a tool for the in vitro study of osteogenesis and
      osteopathology.

PMID- 17518621
TI  - In vitro microdistraction of preosteoblasts: distraction promotes proliferation
      and oscillation promotes differentiation.
AB  - Osteoblast biology is influenced in vivo by a 3-dimensional (3D) extracellular
      matrix that mediates their adhesion and interaction and by a constant state of
      compressive and tensile forces. To study the role of mechanical stress on
      osteoblasts in vitro, these parameters must be addressed. Therefore, this study
      describes the use of a novel, in vitro system that subjects cells to distractive
      and compressive forces in a 3D environment. This system, termed a microdistractor
      system, was used to apply linear forces to 3D collagen type I gels containing
      preosteoblasts. Gels were induced for up to 16 days in osteogenic medium and
      subjected to either constant linear distraction (distraction gels) or to
      repeating cycles of distraction and compression (oscillation gels). The effect of
      these stresses was evaluated over time by measuring proliferation rates, protein
      synthesis (i.e., cellular activity), and osteogenic differentiation levels. While
      linear forces in general appeared to increase protein synthesis, force-specific
      effects on proliferation and differentiation were observed. Specifically,
      distraction forces appeared to enhance MC3T3 proliferation while
      distraction/compressive forces appeared to accelerate their osteogenic
      differentiation program. Therefore, these results suggest that the
      microdistraction system may be an appropriate in vitro system for the study of
      mechanobiology in osteoblast phenotype.

PMID- 17518622
TI  - Platelet-rich plasma: quantification of growth factor levels and the effect on
      growth and differentiation of rat bone marrow cells.
AB  - Platelet-rich plasma (PRP) is a new application of tissue engineering and a
      developing area for clinicians and researchers. It is a storage vehicle of growth
      factors (GFs) such as platelet-derived growth factor (PDGF)- AA, -BB, -AB;
      transforming growth factor (TGF)-beta1 and -2; platelet-derived epidermal growth
      factor (PDEGF); platelet-derived angiogenesis factor (PDAF); insulin growth
      factor-1 (IGF-1); and platelet factor- 4 (PF-4), which are known to influence
      bone regeneration. However, animal and clinical studies reveal different results
      with the use of PRP and its effect on bone healing. This could be due to the
      differences between species, that is, differences between species in GF
      concentrations or variation in presence of GFs between the various PRPs. In this
      study, rat bone marrow cells were cultured in PRP-coated wells or in uncoated
      wells for 16 days in osteogenic medium, and analyzed on cell growth (DNA content)
      and cell differentiation (alkaline phosphatase [ALP] activity, calcium content,
      scanning electron microscopy, and QPCR). The concentrations of TGF-beta1, PDGF
      AA, PDGF-AB, and PDGF-BB in rat, goat, and human PRP were subsequently
      determined. The results showed that PRP stimulated initial cell growth and had no
      effect on ALP activity. The calcium measurements showed a significant increase in
      calcium at days 8, 12, and 16. The real-time PCR results showed that PRP
      upregulated osteocalcin at day 1 and collagen type I at day 8. Overall, the
      immunoassays revealed that human PRP contained higher concentrations of growth
      factors per platelet compared to rat and goat PRP. Goat PRP showed higher
      concentrations of growth factors per platelet as compared to rat PRP except for
      PDGF-BB, which had a higher concentration in rat PRP. TGF-beta1 was the most
      abundant growth factor in all 3 PRPs. On the basis of our results, we conclude
      that platelet-rich plasma contains osteo-inductive growth factors, which are
      probably species related. However, we cannot generalize the results because of
      large intraspecies variations. Further, we conclude that rat PRP gel stimulates
      initial growth and differentiation of rat bone marrow cells in vitro.

PMID- 17518623
TI  - Evaluation of tissue-engineered vascular autografts.
AB  - This study evaluated the endothelial function and mechanical properties of tissue
      engineered vascular autografts (TEVAs) constructed with autologous mononuclear
      bone marrow cells (MN-BMCs) and a biodegradable scaffold using a canine inferior
      vena cava (IVC) model. MN-BMCs were obtained from a dog and seeded onto a
      biodegradable tubular scaffold consisting of polyglycolide fiber and poly(L
      lactide-co-epsilon-caprolactone) sponge. This scaffold was implanted in the IVC
      of the same dog on the day of surgery. TEVAs were analyzed biochemically,
      biomechanically, and histologically after implantation. When TEVAs were explanted
      and stimulated with acetylcholine at 1 month, they produced nitrates and nitrites
      dose dependently. N(G)-nitro-L-arginine methylester significantly inhibited these
      reactions. With stimulation by acetylcholine, factor VIII-positive cells of TEVAs
      produced endothelial nitric oxide synthase proteins, and the ratio of endothelial
      nitric oxide synthase/s17 mRNA was similar among native IVC and TEVAs 1 and 3
      months after implantation. TEVAs had biochemical properties and wall thickness
      similar to those of native IVC at 6 months after implantation, and tolerated
      venous pressure well without any problems such as calcification. The number of
      inflammatory cells in TEVAs and the ratio of CD4/s17 mRNA decreased significantly
      with time. These results indicate that TEVAs are a biocompatible material with
      functional endothelial cells and biomechanical properties and do not have
      unwanted side effects.

PMID- 17518624
TI  - Monitoring mesenchymal stromal cell developmental stage to apply on-time
      mechanical stimulation for ligament tissue engineering.
AB  - To evaluate the appropriate time frame for applying mechanical stimuli to induce
      mesenchymal stromal cell (MSC) differentiation for ligament tissue engineering,
      developmental cell phenotypes were monitored during a period of in vitro culture.
      MSCs were seeded onto surface-modified silk fibroin fiber matrices and cultured
      in Petri dishes for 15 days. Cell metabolic activity, morphology, and gene
      expression of extracellular matrix (ECM) proteins (collagen type I and III and
      fibronectin), ECM receptors (integrins alpha-2, alpha-5, and beta-1), and heat
      shock protein 70 (HSP-70) were monitored during the culture of MSC. MSCs showed
      fluctuations in cell metabolic activity, ECM, integrin, and HSP-70 transcription
      potentially correlating to innate developmental processes. Cellular response to
      mechanical stimulation was dependent on the stage of cell development. At day 9,
      when levels of cell metabolic activity, ECM, integrin, and HSP-70 transcription
      peaked, mechanical stimulation increased MSC metabolic activity, alignment, and
      collagen production. Mechanical stimulation applied at day 1 and 3 showed
      detrimental effects on MSCs seeded on silk matrices. The results presented in
      this study identify a unique correlation between innate MSC development processes
      on a surface-modified silk matrix and dynamic environmental signaling.

PMID- 17518625
TI  - Differentiation of dental pulp stem cells into regular-shaped dentin-pulp complex
      induced by tooth germ cell conditioned medium.
AB  - Investigations of the odontoblast phenotype are hindered by obstacles such as the
      limited number of odontoblasts within the dental pulp and the difficulty in
      purification of these cells. Therefore, it is necessary to develop a cell culture
      system in which the local environment is inductive and can promote dental pulp
      stem cells (DPSCs) to differentiate into odontoblast lineage. In this study, we
      investigated the effect of conditioned medium from developing tooth germ cells
      (TGCs) on the differentiation and dentinogenesis of DPSCs both in vitro and in
      vivo. DPSCs were enzymatically isolated from the lower incisors of 4-week-old
      Sprague-Dawley rats and co-cultured with TGC conditioned medium (TGC-CM). The
      cell phenotype of induced DPSCs presents many features of odontoblasts, as
      assessed by the morphologic appearance, cell cycle modification, increased
      alkaline phosphatase level, synthesis of dentin sialoprotein, type I collagen and
      several other noncollagenous proteins, expression of the dentin
      sialophosphoprotein and dentin matrix protein 1 genes, and the formation of
      mineralized nodules in vitro. The induced DPSC pellets in vivo generated a
      regular-shaped dentin-pulp complex containing distinct dentinal tubules and
      predentin, while untreated pellets spontaneously differentiated into bone-like
      tissues. To our knowledge, this is the first study to mimic the dentinogenic
      microenvironment from TGCs in vitro, and our data suggest that TGC-CM creates the
      most odontogenic microenvironment, a feature essential and effective for the
      regular dentinogenesis mediated by DPSCs.

PMID- 17518626
TI  - An electromagnetic compressive force by cell exciter stimulates chondrogenic
      differentiation of bone marrow-derived mesenchymal stem cells.
AB  - In this study, we present a biological micro-electromechanical system and its
      application to the chondrogenic differentiation of rabbit bone marrow-derived
      mesenchymal stem cells (MSCs). Actuated by an electromagnetic force, the micro
      cell exciter was designed to deliver a cyclic compressive load (CCL) with various
      magnitudes. Two major parts in the system are an actuator and a cartridge-type
      chamber. The former has a permanent magnet and coil, and the latter is equipped
      with 7 sample dishes and 7 metal caps. Mixed with a 2.4% alginate solution, the
      alginate/MSC layers were positioned in the sample dishes; the caps contained
      chondrogenic defined medium without transforming growth factor-beta (TGF-beta).
      Once powered, the actuator coil-derived electromagnetic force pulled the metal
      caps down, compressing the samples. The cyclic load was given at 1-Hz frequency
      for 10 min twice a day. Samples in the dishes without a cap served as a control.
      The samples were analyzed at 3, 5, and 7 days after stimulation for cell
      viability, biochemical assays, histologic features, immunohistochemistry, and
      gene expression of the chondrogenic markers. Applied to the alginate/MSC layer,
      the CCL system enhanced the synthesis of cartilage-specific matrix proteins and
      the chondrogenic markers, such as aggrecan, type II collagen, and Sox9. We found
      that the micromechanically exerted CCL by the cell exciter was very effective in
      enhancing the chondrogenic differentiation of MSCs, even without using exogenous
      TGF-beta.

PMID- 17518627
TI  - Use of an in vitro model of tissue-engineered skin to investigate the mechanism
      of skin graft contraction.
AB  - Skin graft contraction leading to loss of joint mobility and cosmetic deformity
      remains a major clinical problem. In this study we used a tissue-engineered model
      of human skin, based on sterilized human adult dermis seeded with keratinocytes
      and fibroblasts, which contracts by up to 60% over 28 days in vitro, as a model
      to investigate the mechanism of skin contraction. Pharmacologic agents modifying
      collagen synthesis, degradation, and cross-linking were examined for their effect
      on contraction. Collagen synthesis and degradation were determined using
      immunoassay techniques. The results show that skin contraction was not dependent
      on inhibition of collagen synthesis or stimulation of collagen degradation, but
      was related to collagen remodelling. Thus, reducing dermal pliability with
      glutaraldehyde inhibited the ability of cells to contract the dermis. So did
      inhibition of matrix metalloproteinases and inhibition of lysyl oxidase-mediated
      collagen cross-linking, but not transglutaminase-mediated cross-linking. In
      summary, this in vitro model of human skin has allowed us to identify specific
      cross-linking pathways as possible pharmacologic targets for prevention of graft
      contracture in vivo.

PMID- 17518628
TI  - In vitro liver tissue model established from transgenic mice: role of HIF-1alpha
      on hypoxic gene expression.
AB  - The instability of the hepatocyte phenotype in vitro has limited the ability to
      quantitatively investigate regulation of stress responses of the liver. Here, we
      adopt a tissue-engineering approach to form stable liver tissue in vitro by
      forming collagen "sandwich" cultures of transgenic murine hepatocytes harboring a
      regulatory gene of interest flanked by loxP sites. The floxed gene is excised in
      a subset of cultures by transfection with adenovirus carrying the gene for Cre
      recombinase, thereby generating wild-type and null liver tissues from a single
      animal. In this study, we specifically investigated the role of hypoxia inducible
      factor 1 alpha (HIF-1alpha) in the hepatocellular response to hypoxia. Using high
      density oligonucleotide arrays, we examined genome-wide gene expression after 8 h
      of hypoxia in wild-type and HIF- 1alpha null hepatocyte cultures. We identified
      more than 130 genes differentially expressed under hypoxia involved in metabolic
      adaptation, angiogenic signaling, immediate early response, and cell cycle
      regulation. Real-time polymerase chain reaction analysis verified that known
      hypoxia-responsive genes such as glucose transporter-1 and vascular endothelial
      growth factor were induced in a HIF-1alpha-dependent manner under hypoxia. Our
      results demonstrate the potential to integrate in vitro tissue models with
      transgenic and microarray technologies for the study of physiologic stress
      responses.

PMID- 17518629
TI  - Structure and functional evaluation of tendon-skeletal muscle constructs
      engineered in vitro.
AB  - During muscle contraction, the integrity of the myotendinous junction (MTJ) is
      important for the transmission of force from muscle to tendon. We evaluated the
      contractile and structural characteristics of 3-dimensional (3-D) skeletal muscle
      constructs co-cultured with engineered self-organized tendon constructs (n = 4),
      or segments of adult (n = 4) or fetal (n = 5) rat-tail tendon. We hypothesized
      that the co-culture of tendon and muscle would produce constructs with viable
      muscle-tendon interfaces that remain intact during generation of force. Construct
      diameter (lm) and maximum isometric force (microN) were measured, and specific
      force (kPa) was determined. After measure of force, constructs were loaded at a
      constant strain rate until failure and surface strains were recorded optically
      across the tendon, the muscle and the interface and used to determine the tangent
      modulus (passive stiffness) of the construct. Frozen samples were used for
      Trichrome Masson staining and immunofluorescent analysis of the MTJ-specific
      protein paxillin. No differences were observed between the groups with respect to
      diameter, maximum force, or specific force. The MTJ was robust and withstood
      tensile loading beyond the physiological strain range. The majority of the
      constructs failed in the muscle region. At the MTJ, there is an increase in the
      expression and localization of paxillin. In conclusion, using 3 sources of tendon
      tissue, we successfully engineered 3-D muscle-tendon constructs with functionally
      viable MTJ, characterized by structural features and protein expression patterns
      resembling neonatal MTJs in vivo.

PMID- 17518630
TI  - Mechanical loading modulates the differentiation state of vascular smooth muscle
      cells.
AB  - The cause underlying the onset of stenosis after vascular reconstruction is not
      well understood. In the present study, we evaluated the effect of mechanical
      unloading on the differentiation state of human vascular smooth muscle cells
      (hVSMCs) using a tissue-engineered vascular media (TEVM). hVSMCs cultured in a
      mechanically loaded three-dimensional environment, known as a living tissue
      sheet, had a higher differentiated state than cells grown on plastic. When the
      living tissue sheet was detached from its support, the release of the residual
      stress resulted in a mechanical unloading and cells within the extracellular
      matrix (ECM) dedifferentiated as shown by downregulation of differentiation
      markers. The relaxed living tissue sheet can be rolled onto a tubular mandrel to
      form a TEVM. The rolling procedure resulted in the reintroduction of a mechanical
      load leading to a cohesive compacted tissue. During this period, cells gradually
      redifferentiated and aligned circumferentially to the tubular support. Our
      results suggest that differentiation of hVSMCs can be driven by mechanical
      loading and may occur simultaneously in the absence of other cell types. The
      extrapolation of our results to the clinical context suggests the hypothesis that
      hVSMCs may adopt a proliferative phenotype resulting from the mechanical
      unloading of explanted blood vessels during vascular reconstruction. Therefore,
      we propose that this mechanical unloading may play an important role in the onset
      of vascular graft stenosis.

PMID- 17518631
TI  - Effects of simple and complex motion patterns on gene expression of chondrocytes
      seeded in 3D scaffolds.
AB  - This study investigated the effect of unidirectional and multidirectional motion
      patterns on gene expression and molecule release of chondrocyte-seeded 3D
      scaffolds. Resorbable porous polyurethane scaffolds were seeded with bovine
      articular chondrocytes and exposed to dynamic compression, applied with a ceramic
      hip ball, alone (group 1), with superimposed rotation of the scaffold around its
      cylindrical axis (group 2), oscillation of the ball over the scaffold surface
      (group 3), or oscillation of ball and scaffold in phase difference (group 4).
      Compared with group 1, the proteoglycan 4 (PRG4) and cartilage oligomeric matrix
      protein (COMP) mRNA expression levels were markedly increased by ball oscillation
      (groups 3 and 4). Furthermore, the collagen type II mRNA expression was enhanced
      in the groups 3 and 4, while the aggrecan and tissue inhibitor of
      metalloproteinase-3 (TIMP-3) mRNA expression levels were upregulated by
      multidirectional articular motion (group 4). Ball oscillation (groups 3 and 4)
      also increased the release of PRG4, COMP, and hyaluronan (HA) into the culture
      media. This indicates that the applied stimuli can contribute to the maintenance
      of the chondrocytic phenotype of the cells. The mechanical effects causing cell
      stimulation by applied surface motion might be related to fluid film buildup
      and/or frictional shear at the scaffold-ball interface. It is suggested that the
      oscillating ball drags the fluid into the joint space, thereby causing
      biophysical effects similar to those of fluid flow.

PMID- 17518632
TI  - Effect of recombinant human bone morphogenetic protein-2 on mandibular
      distraction at different rates in a rabbit model.
AB  - This study aims to evaluate the effect of recombinant human bone morphogenetic
      protein-2 (rhBMP-2) on mandibular distraction at routine and rapid distraction
      rates. Eighteen New Zealand white rabbits were assigned to 2 groups, 1 treated at
      a routine distraction rate (0.9 mm/d) and the other at a rapid distraction rate
      (2.7 mm/d). rhBMP-2 was injected into 1 side of the distraction regenerate at the
      end of the active distraction period; the contralateral side was used as a
      control. The distraction regenerates were analyzed by plain radiography,
      microcomputed tomography, and histologic examination. The results showed that
      rhBMP-2 can promote bone formation at both rapid and routine distraction rates,
      but no statistically significant difference was observed between the bone
      morphogenetic protein injection sides of the rapid and routine distraction
      groups. In conclusion, the study indicates that rhBMP-2 can enhance bone
      ossification at both routine and rapid distraction rates. The addition of rhBMP-2
      seems to be able to compensate for the rapid distraction rate in mandibular
      distraction osteogenesis. Further longterm follow-up and mechanical strength test
      for the support of implants or conventional prostheses are necessary.

PMID- 17518633
TI  - Video-gait analysis of functional recovery of nerve repaired with chitosan nerve
      guides.
AB  - Quantitative analysis of peripheral nerve regeneration using nerve guides is
      commonly evaluated through histomorphometry and walking track analysis. We
      conducted a unique assessment of functional sciatic nerve recovery treated with
      chitosan nerve guides. We used video-gait analysis to evaluate the extent of
      functional nerve recovery by measuring the ankle angle at different gait cycle
      phases. We also correlated the gastrocnemius muscle weight measurements and
      histological analysis to functional nerve recovery. The chitosan group showed
      increased functional improvement compared to the control groups at the end of a
      12-week period ( p < 0.05). Although both control and chitosan angle measurements
      were lower than those recorded for presurgery animals, the angle measurements
      significantly improved over the 12-week period. Stance phase duration of the gait
      cycle was also recorded, which showed a significant increase over the 12-week
      time period. The muscle weight parameter indicated a significant decrease in
      muscle atrophy and restoration of functional strength. Histological analysis
      revealed that the chitosan nerve guide provided significantly increased axonal
      growth. The functional results indicated that chitosan nerve guides enhanced
      functional improvement over no repair processes.

PMID- 17518634
TI  - Effect of a synthetic extracellular matrix on vocal fold lamina propria gene
      expression in early wound healing.
AB  - An improved understanding of molecular response in the vocal folds to a synthetic
      extracellular matrix (sECM) during early wound repair is essential for
      understanding functional improvement of the tissue and implementation of future
      tissue-engineering strategies. The present study used real-time reverse
      transcriptase polymerase chain reaction to measure transcript expression of
      selected markers (procollagen alpha 2 type I, fibronectin, fibromodulin,
      hyaluronan synthase 2, and hyaluronidase 2) in 20 rabbits that underwent vocal
      fold biopsy bilaterally. After the biopsy, Carbylan-GSX 5% was injected
      immediately into the left vocal fold, and saline was injected into the right
      vocal fold. Two unwounded normal rabbit larynges were also harvested. Animals
      were sacrificed at days 1, 3, 5, and 10 post-surgery. At days 1, 3, and 10, no
      significant differences were found between the Carbylan-GSX-treated and saline
      treated groups. At day 5, significant differences in procollagen (p = 0.02),
      fibronectin (p = 0.02), and transforming growth factor beta1 (p = 0.02) between
      the Carbylan-GSX-treated and saline-treated groups were measured. The presence of
      a sECM in the wound bed during the early stages of repair amplified the normal
      rabbit vocal fold wound-healing response over a short period of time. This
      amplification provided an optimal environment for tissue regeneration and may
      lead to the recovery of the functional biomechanical properties of the vocal
      folds necessary for voice production.

PMID- 17518635
TI  - Repair of porcine articular osteochondral defects in non-weightbearing areas with
      autologous bone marrow stromal cells.
AB  - In vivo niche is known to play important roles in terminal differentiation of
      implanted bone marrow stromal cells (BMSCs). This study explored the feasibility
      of repairing articular osteochondral defects using autologous BMSCs and
      biodegradable polymers. BMSCs from 18 hybrid pigs' marrows were either treated
      with dexamethasone (40 ng/mL) alone or chondrogenically induced with
      dexamethasone and transforming growth factor-beta1 (10 ng/mL). The cells were
      seeded respectively onto polylactic acid (PLA)- coated polyglycolic acid (PGA)
      scaffolds. Four osteochondral defects in each animal were created at non
      weightbearing areas of knee joints (2/each side) and were respectively repaired
      by a chondrogenically induced BMSC-PGA/PLA construct in experimental group (Exp),
      by a dexamethasone-treated BMSC-PGA/PLA construct in control 1 group (Ctrl 1), by
      a PGA/PLA construct alone in control 2 group (Ctrl 2), or left unrepaired in
      control 3 group (Ctrl 3). To trace the implanted cells, green fluorescent protein
      (GFP)- labeled BMSCs were implanted in 2 animals. Gross view and histology showed
      that Exp and Ctrl 1 (with cell implantation) achieved better reparative results
      than Ctrl 2 and Ctrl 3 (without cell implantation) in terms of the reparative
      level and the restoration of the histological structure. In addition, 6-month
      results were better than 3-month results in all 4 groups. In Exp, 11 of 16
      defects were completely repaired by hyaline cartilage and cancellous bone. In
      Ctrl 1, 11 of 16 defects were repaired by fibrocartilage and cancellous bone,
      although the repair with hyaline cartilage and cancellous bone was observed in 5
      of 16 defects. In contrast, no obvious repair or only fibrotic tissue was
      observed in Ctrl 2 and Ctrl 3. The compressive moduli of repaired cartilage in
      Exp reached 80.27% of the normal amount at 6 months, with a high level of
      glycosaminoglycan (GAG) content (no statistical difference from normal). In Ctrl
      1, the compressive moduli and GAG content were 62.69% and 78.03% of normal
      levels, respectively. More importantly, GFP-labeled cells were detected in the
      engineered cartilage and the repaired subchondral bone. These results strongly
      indicate that the implanted BMSCs can differentiate into either chondrocytes or
      osteoblasts and repair articular osteochondral defects by forming engineered
      cartilage and engineered bone.

PMID- 17518636
TI  - Engineering of biologically active living heart valve leaflets using human
      umbilical cord-derived progenitor cells.
AB  - This study demonstrates the engineering of biologically active heart valve
      leaflets using prenatally available human umbilical cord-derived progenitor cells
      as the only cell source. Wharton's Jelly-derived cells and umbilical cord blood
      derived endothelial progenitor cells were subsequently seeded on biodegradable
      scaffolds and cultured in a biomimetic system under biochemical or mechanical
      stimulation or both. Depending on the stimulation, leaflets showed mature layered
      tissue formation with functional endothelia and extracellular matrix production
      comparable with that of native tissues. This demonstrates the feasibility of
      heart valve leaflet fabrication from prenatal umbilical cord-derived progenitor
      cells as a further step in overcoming the lack of living autologous replacements
      with growth and regeneration potential for the repair of congenital malformation.

PMID- 17518637
TI  - Expansion of undifferentiated murine embryonic stem cells as aggregates in
      suspension culture bioreactors.
AB  - Pluripotent embryonic stem cells (ESCs) have recently been considered as a
      primary material for regenerating tissues lost to injuries and degenerative
      diseases. For clinical implementation of this technology, a quality controlled,
      reproducible culture system is necessary for the expansion and differentiation of
      the cells. Used in many bioprocess applications, suspension bioreactors have
      gained considerable attention for the regulated large-scale expansion of cells.
      The current study presents a bioreactor process for the large-scale expansion of
      undifferentiated murine ESCs as aggregates. In this system, the level of ESC
      aggregation and differentiation was effectively controlled by adjusting shear
      forces and inoculation density, achieving a 31-fold expansion in 5 days.
      Pluripotency markers Oct-4, Nanog, SSEA-1, ALP, and rex-1 were assessed using
      flow cytometry analysis and gene expression profiles and showed that the
      undifferentiated nature of the cells within the ESC aggregates was maintained.
      Colony-forming efficiencies and embryoid body formation tests of the expanded
      cultures demonstrated that characteristic functional attributes of
      undifferentiated cells were not lost. Overcoming a major impediment in the area
      of ESC expansion, this study describes a successful process for the controlled
      and reproducible largescale expansion of ESCs using suspension culture
      bioreactors.

PMID- 17518638
TI  - Magnetically-guided self-assembly of fibrin matrices with ordered nano-scale
      structure for tissue engineering.
AB  - The development of effective biological scaffold materials for tissue engineering
      and regenerative medicine applications hinges on the ability to present precise
      environmental cues to specific cell populations to guide their position and
      function. Natural extracellular matrices have an ordered nano-scale structure
      that can modulate cell behaviors critical for developmental control, including
      directional cell motility. Here we describe a method for fabricating fibrin gels
      with defined architecture on the nanometer scale in which magnetic forces are
      used to position thrombin-coated magnetic micro-beads in a defined 2-dimensional
      array and thereby guide the self-assembly of fibrin fibrils through catalytic
      cleavage of soluble fibrinogen substrate. Time-lapse and confocal microscopy
      confirmed that fibrin fibrils nucleate near the surface of the thrombin-coated
      beads and extend out in a radial direction to form these gels. When controlled
      magnetic fields were used to position the beads in hexagonal arrays, the fibrin
      nano-fibrils that polymerized from the beads oriented preferentially along the
      bead--bead axes in a geodesic (minimal path) pattern. These biocompatible
      scaffolds supported adhesion and spreading of human microvascular endothelial
      cells, which exhibited co-alignment of internal actin stress fibers with
      underlying fibrin nano-fibrils within some membrane extensions at the cell
      periphery. This magnetically-guided, biologically-inspired microfabrication
      system is unique in that large scaffolds may be formed with little starting
      material, and thus it may be useful for in vivo tissue engineering applications
      in the future.

PMID- 17518640
TI  - Growth factor modulation of fibroblast proliferation, differentiation, and
      invasion: implications for tissue valve engineering.
AB  - We have previously shown that transforming growth factor-beta1 (TGF-beta1)
      stimulates transdifferentiation of fibroblasts into smooth muscle alpha-actin
      (alpha-SMA) positive myofibroblasts. However, TGF-beta, as such, is unsuitable
      for effective population of a heart valve matrix, because it dose-dependently
      inhibits growth of fibroblasts. The aim of this study was to investigate
      combinations of other growth factors with TGF-beta to stimulate the proliferation
      of suitably differentiated cells and to enhance their invasion into aortic valve
      matrices. Human dermal mesenchymal cells (hDMC1.1) were treated with combinations
      of growth factors to stimulate these cells to trans-differentiate into
      myofibroblasts, to proliferate, and to invade. Growth factors were chosen after
      expression of their respective receptors was confirmed in hDMC1.1 using reverse
      transcriptase polymerase chain reaction. We combined TGF-beta with several growth
      factors such as insulin-like growth factor (IGF-1, IGF-2), epidermal growth
      factor (EGF), basic fibroblast growth factor (bFGF), and platelet-derived growth
      factor (PDGF-AA, PDGF-BB, and PDGFAB). Nuclear Ki67 staining, MTT assay, and cell
      counting revealed that only EGF and bFGF were capable of overcoming TGF-beta
      induced growth inhibition. However, bFGF but not EGF inhibited TGF-beta-induced
      alpha-SMA expression, as evidenced by immuno-cytochemistry and Western blotting.
      A growth factor cocktail (TGF-beta, EGF, bFGF) has been established that
      maintains TGF-beta-induced trans-differentiation but overcomes TGF-beta-induced
      growth inhibition while stimulating fibroblast proliferation and invasion.

PMID- 17518641
TI  - Effects of common sterilization methods on the structure and properties of
      poly(D,L lactic-co-glycolic acid) scaffolds.
AB  - While methods for the production of scaffolds with the appropriate mechanical
      properties and architecture for tissue engineering are attracting much attention,
      the effects of subsequent sterilization processes on the scaffold properties have
      often been overlooked. This study sought to determine the effects of
      sterilization with ethanol, peracetic acid, ultraviolet irradiation, and
      antibiotic solution on the structure of 50:50 (mol:mol) 65:35, and 85:15 poly(D,L
      lactic-co-glycolic acid [PLGA]) flat-sheet and hollow-fiber scaffolds. All
      methods resulted in scaffold sterilization, but scanning electron microscopy
      revealed deformations to the scaffold surface for all treatments. The extent of
      surface damage increased with treatment duration. This was further investigated
      by measurement of pore sizes, water flux, breaking strain, and Young's modulus.
      External pore size and water flux was found to be increased by all treatments in
      the following order: ethanol (largest), antibiotics, ultraviolet light, and
      peracetic acid. Pore sizes were 0.25 to 0.17 microm and water flux ranged from
      0.01 kg x m(-2) x s(-1) to 3.34 kg x m(-2) x s(-1). For all samples, the Young's
      modulus was 1.0 to 31.1 MPa and breaking strain was 1.2 to 2.4 MPa. The results
      of this study suggest that antibiotic treatment shows the most potential to
      sterilize PLGA hollow fibers for tissue engineering.

PMID- 17518642
TI  - Cartilage-like tissue engineering using silk scaffolds and mesenchymal stem
      cells.
AB  - Silk fibroin scaffolds were studied as a new biomaterial option for tissue
      engineered cartilage-like tissue. Human bone marrow-derived mesenchymal stem
      cells (MSCs) were seeded on silk, collagen, and crosslinked collagen scaffolds
      and cultured for 21 days in serum-free chondrogenic medium. Cells proliferated
      more rapidly on the silk fibroin scaffolds than on the collagen matrices. The
      total content of glycosaminoglycan deposition was three times higher on silk as
      compared to collagen scaffolds. Glycosaminoglycan deposition coincided with
      overexpression of collagen type II and aggrecan genes. Cartilage-like tissue was
      homogeneously distributed throughout the entire silk scaffolds, while on the
      collagen and crosslinked collagen systems tissue formation was restricted to the
      outer rim, leaving a doughnut appearance. Round or angular-shaped cells resided
      in deep lacunae in the silk systems and stained positively for collagen type II.
      The aggregate modulus of the tissue-engineered cartilage constructs was more than
      2-fold higher than that of the unseeded silk scaffold controls. These results
      suggest that silk fibroin scaffolds are suitable biomaterial substrates for
      autologous cartilage tissue engineering in serum-free medium and enable
      mechanical improvements along with compositional features suitable for durable
      implants to generate or regenerate cartilage.

PMID- 17518643
TI  - Tissue-engineered follicles produce live, fertile offspring.
AB  - Oocytes grown in vitro are of low quality and yield few live births, thus
      limiting the ability to store or bank the ova of women wishing to preserve their
      fertility. We applied tissue engineering principles to the culture of immature
      mouse follicles by designing an alginate hydrogel matrix to maintain the oocyte's
      3- dimensional (3D) architecture and cell-cell interactions in vitro. A 3D
      culture mimics the in vivo follicle environment, and hydrogel-encapsulated
      follicles develop mature oocytes within the capacity for fertilization similar to
      that of oocytes matured in vivo. Embryos derived from cultured oocytes fertilized
      in vitro and transferred to pseudopregnant female mice were viable, and both male
      and female offspring were fertile. Our results demonstrate that alginate hydrogel
      based 3D in vitro culture of follicles permits normal growth and development of
      follicles and oocytes. This system creates new opportunities for discovery in
      follicle biology and establishes a core technology for human egg banks for
      preservation of fertility.

PMID- 17518644
TI  - Modulations of 17-beta estradiol on osteogenic and adipogenic differentiations of
      human mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (MSCs) are a promising cell source for tissue
      engineering and regenerative medicine applications. However, effective regulation
      to improve differentiation potentials of MSCs plays a critical role in promoting
      successful tissue formation. Because estrogen has been demonstrated to modulate
      tissue and organ development and differentiation, we hypothesized that adding
      estrogen could effectively improve the multiple differentiation potentials of
      human bone marrow MSCs in vitro. In the present study, 17-beta estradiol (E2) was
      investigated for in vitro osteogenic and adipogenic differentiations of MSCs
      isolated from a healthy male human donor. After MSCs were exposed to osteogenic
      differentiation medium supplemented with E2 at different concentrations,
      osteocalcin expression is upregulated and calcium deposition (21.0%) is
      significantly improved ( p < 0.01; n = 4). Under adipogenic stimulation, E2
      increased 35.4% lipid accumulations more than that of the group without the E2
      supplement ( p < 0.01; n = 4). Estrogen's effect on osteogenesis occurs via
      estrogen receptors (ER)-alpha and -beta, whereas the effect on adipogenesis is
      through ER-alpha. Estrogen's regulation of differentiations of MSCs is dose
      dependent. The present study indicated that estrogen could potentially improve
      the role of MSCs in tissue engineering and regeneration by serving as a modulator
      of differentiation.

PMID- 17518645
TI  - Biomechanical and magnetic resonance characteristics of a cartilage-like
      equivalent generated in a suspension culture.
AB  - OBJECTIVE: To generate a cartilage biomaterial using a suspension culture with
      biophysical properties similar to native articular cartilage. DESIGN: A novel
      cartilage tissue equivalent (CTE) using a no-scaffold, high-density suspension
      culture of neonatal porcine chondrocytes was formed on poly 2-hydroxyethyl
      methacrylate-treated plates for up to 16 weeks. Equilibrium aggregate modulus and
      hydraulic permeability were measured at 8 and 16 weeks using confined compression
      stress relaxation experiments. The CTE proteoglycan composition was characterized
      using sodium and T(1rho) magnetic resonance imaging methods after 8 weeks.
      RESULTS: The resultant CTE produces a biomaterial consistent with a hyaline
      cartilage phenotype in appearance and expression of type II collagen and
      aggrecan. The equilibrium aggregate modulus and permeability for the 8-week
      specimens were 41.6 (standard deviation (SD) 4.3) kPa and 2.85(-13) (SD 2.45(
      13)) m(4)/Ns, respectively, and, for the 16-week specimens, 35.2 (SD 7.6) kPa and
      2.67(-13) (SD 1.06(-13)) m(4)/Ns, respectively. Average sodium concentration of
      the 8-week CTE ranged from 260 to 278 mM and average T(1rho) relaxation times
      from 105 to 107 ms, indicating proteoglycan content similar to that of native
      articular cartilage. CONCLUSION: The high-density culture method produced a CTE
      with characteristics that approach those of native articular cartilage. The CTE
      mechanical properties are similar to those of the native cartilage. The CTE
      developed in this study represents a promising methodological advancement in
      cartilage tissue engineering and cartilage repair.

PMID- 17518646
TI  - Magnetic resonance imaging of ferumoxide-labeled mesenchymal stem cells seeded on
      collagen scaffolds-relevance to tissue engineering.
AB  - Mesenchymal stem cells (MSCs) are a promising candidate cell for tissue
      engineering. Magnetic resonance imaging (MRI) has been proven effective in
      visualizing iron-labeled stem cells; however, the efficiency of this approach for
      visualization of cells seeded on scaffolds intended for use as tissue-engineered
      heart valves has not been assessed. MSCs were labeled by incubating for 48 h with
      ferumoxide and poly-L-lysine as transfecting agent. Any detrimental effect of
      iron labeling on cell viability, proliferation, and differentiation was examined
      using appropriate functional assays. Change in the nuclear magnetic relaxation
      properties of labeled cells was determined using in vitro relaxometry of cells
      seeded in 3-dimensional collagen gels. Images of labeled and non-labeled cells
      seeded onto 1% type I bovine collagen scaffolds were obtained using MRI. The
      presence of intracellular iron in labeled cells was demonstrated using Prussian
      blue staining, confocal microscopy, and electron microscopy. Cell viability,
      proliferation, and differentiation were comparable in labeled and non-labeled
      cells. The T2 relaxation time was 40% to 50% shorter in ferumoxide-labeled cells.
      Labeled cells seeded on scaffolds appeared as areas of reduced signal intensity
      in T2 weighted images. Ferumoxide labeling persisted and remained effective even
      on scans performed 4 weeks after the labeling procedure. Ferumoxide labeling of
      human MSCs seeded on collagen scaffolds is an effective, non-toxic technique for
      visualization of these cells using MRI. This technique appears promising for cell
      tracking in future tissue-engineering applications.

PMID- 17518647
TI  - Templated agarose scaffolds support linear axonal regeneration.
AB  - While several strategies can stimulate axonal regeneration within a site of
      spinal cord injury, the growth of axons is generally disorganized and random.
      Biocompatible scaffolds that guide and maintain the native organization of axons
      regenerating through an injury site could be of importance in enhancing recovery
      of the nervous system after injury. Here we report a novel fabrication process
      for templated agarose nerve guidance scaffolds composed of uniaxial channels of
      precise diameter and wall thickness extending through their full length. When
      tested in an in vivo model of spinal cord injury, scaffolds exhibit excellent
      integration with host tissue and support linear axonal growth through their
      channels. Further, when loaded with bone marrow stromal cells genetically
      engineered to secrete brain-derived neurotrophic factor (BDNF), the number of
      linear penetrating axons is significantly enhanced. The templating process can be
      useful in fabricating nerve guidance scaffolds for both central and peripheral
      nerve injuries, or any materials application requiring a precise array of
      linearly oriented channels.

PMID- 17518648
TI  - Strategies to promote chondrogenesis and osteogenesis from human bone marrow
      cells and articular chondrocytes encapsulated in polysaccharide templates.
AB  - The aim of this study was to synthesize functional in vitro and in vivo 3
      dimensional (3D) constructs using a mix of human mesenchymal populations and
      articular chondrocytes encapsulated in biomineralized polysaccharide templates.
      Single-cell-type populations or mixtures of both cell types were encapsulated in
      alginate/chitosan and cultured within a rotating-bioreactor, perfused bioreactor
      system, or static conditions for 28 days. Within single cell-type populations,
      type II collagen immunopositive cells were present within lacunae in rotating
      bioreactor capsules, with an increased proportion of metabolically active cells
      compared with perfused and static constructs. Biochemical analysis indicated
      significantly increased ( p < 0.05) DNA and protein in rotating-bioreactor
      conditions compared with perfused or static. However, in coculture samples, DNA
      and protein was significantly increased in static cultures owing to the formation
      of large regions of partially mineralized osteoid. This osteoid was found only in
      static cultures and when the ratio of human bone marrow cells to chondrocytes was
      2:1 or, to a lesser extent, 5:1 ratio capsules. Subcutaneous implantation of
      capsules into immunocompromised mice also showed optimal osteoid formation when
      the ratio was 2:1. The current studies demonstrate the pivotal role of robust 3D
      biomimetic microenvironments and indicate the potential to harness the
      interactions between different cell types to create specific tissues.

PMID- 17518649
TI  - Fabrication and characterization of poly(propylene fumarate) scaffolds with
      controlled pore structures using 3-dimensional printing and injection molding.
AB  - Poly(propylene fumarate) (PPF) is an injectable, biodegradable polymer that has
      been used for fabricating preformed scaffolds in tissue engineering applications
      because of in situ crosslinking characteristics. Aiming for understanding the
      effects of pore structure parameters on bone tissue ingrowth, 3-dimensional (3D)
      PPF scaffolds with controlled pore architecture have been produced in this study
      from computer-aided design (CAD) models. We have created original scaffold models
      with 3 pore sizes (300, 600, and 900 microm) and randomly closed 0%, 10%, 20%, or
      30% of total pores from the original models in 3 planes. PPF scaffolds were
      fabricated by a series steps involving 3D printing of support/build constructs,
      dissolving build materials, injecting PPF, and dissolving support materials. To
      investigate the effects of controlled pore size and interconnectivity on
      scaffolds, we compared the porosities between the models and PPF scaffolds
      fabricated thereby, examined pore morphologies in surface and cross-section using
      scanning electron microscopy, and measured permeability using the falling head
      conductivity test. The thermal properties of the resulting scaffolds as well as
      uncrosslinked PPF were determined by differential scanning calorimetry and
      thermogravimetric analysis. Average pore sizes and pore shapes of PPF scaffolds
      with 600- and 900-microm pores were similar to those of CAD models, but they
      depended on directions in those with 300-microm pores. Porosity and permeability
      of PPF scaffolds decreased as the number of closed pores in original models
      increased, particularly when the pore size was 300 microm as the result of low
      porosity and pore occlusion. These results show that 3D printing and injection
      molding technique can be applied to crosslinkable polymers to fabricate 3D porous
      scaffolds with controlled pore structures, porosity, and permeability using their
      CAD models.

PMID- 17518650
TI  - Multilineage differentiation potential of stem cells derived from human dental
      pulp after cryopreservation.
AB  - The current study aimed to prove that human dental pulp stem cells (hDPSCs)
      isolated from the pulp of third molars can show multilineage differentiation
      after cryopreservation. First, hDPSC were isolated via enzymatic procedures, and
      frozen in liquid nitrogen until use. After defrosting, cells were analyzed for
      proliferative potential and the expression of the stem cell marker STRO-1.
      Subsequently, cells were cultured in neurogenic, osteogenic/odontogenic,
      adipogenic, myogenic, and chondrogenic inductive media, and analyzed on basis of
      morphology, immunohistochemistry, and reverse transcriptase-polymerase chain
      reaction (RT-PCR) for specific marker genes. All data were replicated, and the
      results of the primary cells were compared to similar tests with an additional
      primary dental pulp stem cell strain, obtained from the National Institutes of
      Health (NIH). Results showed that our cell population could be maintained for at
      least 25 passages. The existence of stem/ progenitor cells in both cell strains
      was proven by the STRO-1 staining. Under the influence of the 5 different media,
      both cell strains were capable to advance into all 5 differentiation pathways.
      Still differences between both strains were found. In general, our primary
      culture performed better in myogenic differentiation, while the externally
      obtained cells were superior in the odontogenic/osteogenic and chondrogenic
      differentiation pathways. In conclusion, the pulp tissue of the third molar may
      serve as a suitable source of multipotent stem cells for future tissue
      engineering strategies and cell-based therapies, even after cryopreservation.

PMID- 17518651
TI  - Antioxidant functionality in hepatocytes using the enhanced collagen
      extracellular matrix under different oxygen tensions.
AB  - Improvement of O(2) supply in bioartificial liver devices remains a critical
      issue in maintaining hepatocyte viability and functions. Therefore, the current
      study investigates whether enhanced oxygen (O(2)) transport through collagen
      extracellular matrix (ECM) can produce a more stable antioxidant defense in
      different O(2) tensions during prolonged incubation times. Total glutathione
      concentration of cultured hepatocytes in enhanced ECM was significantly higher
      than in normal ECM under the lowest O(2) tension phase (2.60mm of thickness from
      O(2) source), and was also significantly increased in 0.52 mm transport distance
      of hypoxia as compared to normoxic conditions. Catalase and glutathione reductase
      activities for hepatocytes within enhanced ECM were also significantly preserved
      relative to their values for the normal collagen ECM. Specifically, the enhanced
      ECM produced higher activities at a further transport distance (1.56 mm) from the
      O(2) source at the 24 h time-point, and remained higher up to the 96 h incubation
      time. In contrast, the glutathione peroxidase activities in both collagen ECM
      systems were similar. Hepatocyte viability in the enhanced ECM system was also
      consistently greater than that for normal ECM. These results suggest that the
      O(2) enhanced collagen ECM preserves the antioxidant defense system as compared
      to normal collagen ECM, ostensibly via increased micropathways for O(2) transport
      to the hepatocytes.

PMID- 17518652
TI  - Imaging human bone marrow stem cell morphogenesis in polyglycolic acid scaffold
      by multiphoton microscopy.
AB  - The noninvasive imaging of tissue engineering constructs is vital for
      understanding the physiological changes in construct formation and the design of
      improved products for therapeutic purposes. In this work, we use the combination
      of multiphoton autofluorescence and second harmonic generation (SHG) microscopy
      to image the physiological changes to the engineered constructs of human
      mesenchymal stem cells seeded in a polyglycolic acid (PGA) scaffold under
      induction by chondrogenic transforming growth factor-beta3. Without histological
      procedures, we found that multiphoton autofluorescence is useful for imaging the
      PGA scaffold and stem cells while SHG is useful for following the progress of
      extracellular matrix (ECM) formation. We found that the initial ECM formation
      tends to align along the PGA scaffold orientation and progressive induction
      alters the scaffold conformation, indicating that biomechanical forces or the
      chemical environment generated by chondrogenesis is sufficient for scaffold
      reorganization. Our results suggest that in the future this approach may be used
      for real-time monitoring of the physiological processes associated with tissue
      engineering.

PMID- 17518653
TI  - A novel perfusion bioreactor providing a homogenous milieu for tissue
      regeneration.
AB  - We developed a novel perfusion bioreactor that is capable of cultivating multiple
      3-dimensional (3D) cellular constructs in one flow chamber with a total cross
      section area of 20 cm(2). Two unique features integrated into the bioreactor
      provided a homogenous fluid flow along the bioreactor cross-section and maximal
      exposure of the cellular constructs to the perfusing medium. Mathematical
      modeling of the fluid flow regime in the perfusion bioreactor showed that
      integrating a flow-distributing mesh 1.5 cm upstream from the construct
      compartment imposed an equal medium flow and shear stress of 0.6 dynes /cm(2)
      along the entire cell construct cross-section area. The design of 95.8%open-pore
      area fixing nets enabled the exposure of 99.88% of the cell construct volume to
      the perfusing medium. Cardiac cell constructs seeded with physiologically
      relevant cell density (0.7 x 10(8) cells/cm(3)) in alginate scaffolds developed
      into homogenous compacted cardiac tissue, as judged using cell staining with
      fluorescein diacetate and hematoxylin-eosin histology. The cell constructs
      maintained 80% viability for nearly 2 weeks, whereas in static-cultivated cell
      constructs, only 50% of the initial cells remained, as determined according to
      total DNA content and MTT viability assay. Medium perfusion resulted in better
      cell viability, presumably due to the convective-diffusive transport of oxygen,
      compared with oxygen diffusion within the static-cultivated cell constructs, as
      well as due to efficient removal of harmful cell secretions. It is envisioned
      that this bioreactor would be useful for 3D cultivation of different mammalian
      cells for purposes of tissue engineering or production of valuable biologicals.

PMID- 17518654
TI  - Differential expression pattern of extracellular matrix molecules during
      chondrogenesis of mesenchymal stem cells from bone marrow and adipose tissue.
AB  - Adipose-derived adult stem cells (ADASCs) or bone marrow-derived mesenchymal stem
      cells (BMSCs) are considered as alternative cell sources for cell-based cartilage
      repair due to their ability to produce cartilage-specific matrix. This article
      addresses the differential expression pattern of extracellular matrix (ECM)
      molecules in BMSCs or ADASCs following chondrogenic differentiation. Human BMSCs
      or ADASCs were encapsulated in alginate and cultured in TGF-beta1-containing
      medium for 2 or 3 weeks. Chondrospecific mRNA expression was analyzed and
      alternative splicing of alpha(1)-procollagen type II mRNA was monitored via
      reverse transcriptase-polymerase chain reaction (RT-PCR). Corresponding ECM
      synthesis was demonstrated using immunohistochemistry. After chondroinduction,
      expression of collagen type II, type X, COMP and aggrecan mRNA was 3-15-fold
      higher than in ADASCs. The type IIA splicing form of alpha(1)-procollagen type II
      was expressed in both populations, and the type IIB splicing form was exclusively
      detected in BMSCs. In response to TGF-beta, collagen type II and X were secreted
      more strongly by BMSCs than by ADASCs. BMSCs express a more mature phenotype than
      ADASCs after chondroinduction. TGF-beta1 induces alternative splicing of the
      alpha(1)-procollagen type II transcript in BMSCs, but not in ADASCs. These
      findings may direct the development of a cell-specific culture environment either
      to prevent hypertrophy in BMSCs or to promote chondrogenic maturation in ADASCs.

PMID- 17518655
TI  - In vivo osteogenic differentiation of rat bone marrow stromal cells in
      thermosensitive MPEG-PCL diblock copolymer gels.
AB  - Methoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (MPEG-PCL) diblock
      copolymers were prepared by ring-opening polymerization and their phase
      transition behavior characterized as a function of temperature. The MPEG-PCL
      solutions formed a sol at room temperature, and underwent sol-to-gel followed by
      gel-to-sol phase transitions as the temperature was increased. The temperature
      range over which the solutions were in a gel state could be extended simply by
      increasing the PCL chain length in the diblock copolymer. Scanning electron
      microscopy (SEM) images of MPEG-PCL solutions in the sol and gel states revealed
      near-regular and irregular porous structures, respectively. in vitro culture of
      rat bone marrow stromal cells (rBMSCs) on gel surfaces exhibited mostly round
      cells after 1 day of incubation. SEM images of the attached cells clearly showed
      the cell body and anchoring filopodia. Injection of room-temperature diblock
      copolymer solutions into Sprague-Dawley rats produced a gel at body temperature.
      In situ gel-forming scaffolds in vivo were successfully fabricated by simple
      subcutaneous injection of MPEG-PCL diblock copolymer solutions. The gel implants
      retained their original shape for 4 weeks without in- flammation at the injection
      site. Gel implants removed after 4 weeks were found to be surrounded by a thin
      fibrous capsule consisting of fibroblasts and blood vessels cells. Hematoxylin
      and eosin (H&E) and von Kossa staining revealed bone formation in gel implants
      containing both rBMSCs and dexamethasone, with the degree of bone formation
      increasing markedly with increasing dexamethasone concentration. Thus, our
      results show that in situ gel scaffolds fabricated from MPEG-PCL diblock
      copolymer solutions containing dexamethasone enable multipotent rBMSCs to produce
      viable bone when injected into rats.

PMID- 17518656
TI  - Mesenchymal stem cells enhance angiogenesis in mechanically viable
      prevascularized tissues via early matrix metalloproteinase upregulation.
AB  - Angiogenesis, the sprouting of new blood vessels from existing vasculature, is a
      complex biological process of interest to both the treatment of numerous
      pathologies and the creation of thick engineered tissues. In the context of
      tissue engineering, one potential solution to the diffusion limitation is to
      create a vascular network in vitro that can subsequently anastomose with the host
      after implantation, allowing the implantation of thicker, more complex tissues.
      In this study, the ability of endothelial cells to sprout and form stable
      vascular networks in 3-dimensional (3D) fibrin matrices was investigated as a
      function of matrix density in a prevascularized tissue model. The results
      demonstrate that while increasing matrix density leads to a nearly 7-fold
      increase in compressive stiffness, vascular sprouting is virtually eliminated in
      the most dense matrix condition. However, the addition of human mesenchymal stem
      cells (HMSCs) to the denser matrices reverses this effect, resulting in an up to
      a 7-fold increase in network formation. Although the matrix metalloproteinases
      (MMPs) MMP-2, MMP-9, and MT1-MMP are all upregulated early on with the addition
      of HMSCs, MT1-MMP appears to play a particularly important role in the observed
      angiogenic response among these proteases. This study provides a means to design
      stiffer prevascularized tissues utilizing naturally derived substrates, and its
      results may yield new mechanistic insights into stem cell-based angiogenic
      therapies.

PMID- 17518657
TI  - Gene expression profiling reveals platelet-derived growth factor receptor alpha
      as a target of cell contact-dependent gene regulation in an endothelial cell
      osteoblast co-culture model.
AB  - Angiogenesis plays an important role in bone development, repair, and
      remodelling. Neovascularization is furthermore a crucial step in bone tissue
      engineering because implantation of voluminous grafts without sufficient
      vascularity results in hypoxic cell death of the engineered tissue. We have
      previously described a co-cultivation system of human primary osteoblasts and
      human primary endothelial cells that was developed to improve neovascularization
      in bone tissue-engineering applications. In our present study, we have performed
      complementary deoxyribonucleic acid microarray analysis to analyze putative
      changes in osteoblastic gene expression upon co-cultivation of osteoblasts and
      endothelial cells. Transcriptional profiling revealed upregulation of 79 genes
      and downregulation of 62 genes in osteoblasts after co-cultivation with
      endothelial cells. To verify the microarray data, quantitative real-time reverse
      transcriptase polymerase chain reaction was carried out on selected genes. The
      expression of the platelet-derived growth factor receptor alpha gene in
      osteoblasts was analyzed in more detail, revealing that a cell contact-dependent
      mechanism, and not paracrine-acting diffusible factors, mediates the
      downregulation of this receptor in osteoblasts upon co-cultivation with
      endothelial cells. In summary, the data demonstrate complex gene-regulation
      mechanisms between endothelial cells and osteoblasts that are likely to play a
      role in bone morphogenesis.

PMID- 17518658
TI  - Sequential growth factor stimulation of bone marrow stromal cells in extended
      culture.
AB  - The sequence of applied biochemical stimulation in developing ligament tissue
      cultures in vitro offers the potential to intricately control cell behavior
      following the template of native tissue development. Previous studies have
      identified and enhanced ligament tissue development as defined by matrix in
      growth, upregulation of mRNA transcripts for metalloproteinase-2 (MMP-2),
      collagen types I and III, and collagen type I production. We hypothesize that
      sequential application of growth factors through extended culture will reinforce
      the effectiveness of basic fibroblast growth factor and transforming growth
      factor beta (bFGF/TGF-beta) as the optimal growth factor regimen. Bone marrow
      stromal cells (BMSCs) were seeded on RGD-coupled silk fiber matrices and cultured
      in bFGF, epidermal growth factor (EGF), or growth factor-free control for the
      first 5 days of culture. On day 5, cultures were stimulated with TGF-beta
      supplemented medium for a total of 28 days. Results indicated enhanced matrix in
      growth and collagen type I produced with extended culture, most notably in
      mitogen / TGF-beta-stimulated cultures. Matrix development attained through
      extended static culture will support future study leading to the transition and
      addition of mechanical stimulation for optimized ligament tissue production.

PMID- 17518659
TI  - Interleukin-1beta increases elasticity of human bioartificial tendons.
AB  - Stiffness is an important mechanical property of connective tissues, especially
      for tissues subjected to cyclic strain in vivo, such as tendons. Therefore,
      modulation of material properties of native or engineered tissues is an important
      consideration for tissue repair. Interleukin 1-beta (IL-1beta) is a cytokine most
      often associated in connective tissues with induction of matrix
      metalloproteinases and matrix destruction. However, IL-1beta may also be involved
      in constructive remodeling and confer a cell survival value to tenocytes. In this
      study, we investigated the effects of IL-1beta on the properties of human
      tenocyte-populated bioartificial tendons (BATs) fabricated in a novel three
      dimensional (3D) culture system. IL-1beta treatment reduced the ultimate tensile
      strength and elastic modulus of BATs and increased the maximum strain. IL-1beta
      at low doses (1, 10 pM) upregulated elastin expression and at a high dose (100
      pM) downregulated type I collagen expression. Matrix metalloproteinases, which
      are involved in matrix remodeling, were also upregulated by IL-1beta. The
      increased elasticity prevented BATs from rupture caused by applied strain. The
      results in this study suggest that IL-1beta may act as a defense/survival factor
      in response to applied mechanical loading. The balance between cell intrinsic
      strain and external matrix strain is important for maintaining the integrity of
      tendons.

PMID- 17518660
TI  - Inhibition of histone acetylation as a tool in bone tissue engineering.
AB  - Our approach to bone tissue engineering is the in vitro expansion and osteogenic
      differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) and
      their subsequent implantation on porous ceramic materials. Current osteogenic
      differentiation protocols use dexamethasone to initiate the osteogenic process,
      thus ignoring the multiple signaling pathways that control osteogenesis in vivo.
      Supporting osteogenesis at multiple stages might further enhance the bone-forming
      capacity of hMSCs. As reported previously, inhibition of so-called histone
      deacetylases (HDACs) stimulates osteoblast maturation, and in this report, we
      investigated whether trichostatin A (TSA), a widely used HDAC inhibitor, can be
      implemented in bone tissue engineering. We confirmed that TSA treatment of hMSCs
      results in increased expression of alkaline phosphatase (ALP) with concomitant
      increase in mineralization. Flow cytometry demonstrated that TSA increases the
      percentage of ALP-positive hMSCs as well as their average ALP expression level,
      but the robustness of the response differs between donors. Unfortunately, TSA has
      a profound negative effect on cell proliferation, so we investigated whether
      hMSCs respond to TSA after reaching confluence. Confluent hMSCs on tissue culture
      plastic displayed enhanced ALP expression. Therefore, we seeded TSA-treated hMSCs
      onto ceramic particles and analyzed ectopic bone formation upon implantation in
      immune-deficient mice. Unfortunately, TSA-treated hMSCs did not display better
      bone formation in vivo than control cells. Finally, we observed that TSA
      treatment strongly enhanced bone formation of ex vivo cultured mouse calvaria,
      which warrants further exploration of TSA in bone tissue engineering.

PMID- 17518661
TI  - Re-engineering primary epithelial cells from rhesus monkey parotid glands for use
      in developing an artificial salivary gland.
AB  - There is no satisfactory conventional treatment for patients who experience
      irreversible salivary gland damage after therapeutic radiation for head and neck
      cancer or because of Sjogren's syndrome. Additionally, if most parenchyma is
      lost, these patients also are not candidates for evolving gene transfer
      strategies. To help such patients, several years ago we began to develop an
      artificial salivary gland. In the present study, we used a non-human primate
      tissue source, parotid glands from rhesus monkeys, to obtain potential autologous
      graft cells for development of a prototype device for in situ testing. Herein, we
      present 3 major findings. First, we show that primary cultures of rhesus parotid
      gland (RPG) cells are capable of attaining a polarized orientation, with
      Na(+)/K(+)-adenosine triphosphatase, zonula occludens-1, and claudin-1
      distributed in specific domains appropriate for epithelial cells. Second, we show
      that RPG cells exhibit 2 essential epithelial functions required for graft cells
      in an artificial salivary gland device (i.e., an effective barrier to
      paracellular water flow and the generation of a moderate transepithelial
      electrical resistance). Third, we show that RPG cells can express functional
      water channels, capable of mediating directional fluid movement, after
      transduction by adenoviral and adeno-associated virus type 2 vectors. Together
      these results demonstrate that it is feasible to individually prepare RPG cells
      for eventual use in a prototype artificial salivary gland.

PMID- 17518662
TI  - Antibacterial activity within degradation products of biological scaffolds
      composed of extracellular matrix.
AB  - Biological scaffolds composed of extracellular matrix (ECM) have been shown to be
      resistant to deliberate bacterial contamination in preclinical in vivo studies.
      The present study evaluated the degradation products resulting from the acid
      digestion of ECM scaffolds for antibacterial effects against clinical strains of
      Staphylococcus aureus and Escherichia coli. The ECM scaffolds were derived from
      porcine urinary bladder (UBM-ECM) and liver (L-ECM). These biological scaffolds
      were digested with acid at high temperatures, fractionated using ammonium sulfate
      precipitation, and tested for antibacterial activity in a standardized in vitro
      assay. Degradation products from both UBM-ECM and L-ECM demonstrated
      antibacterial activity against both S. aureus and E. coli. Specific ammonium
      sulfate fractions that showed antimicrobial activity varied for the 2 different
      ECM scaffold types. The results of this study suggest that several different low
      molecular-weight peptides with antibacterial activity exist within ECM and that
      these peptides may help explain the resistance to bacterial infection provided by
      such biological scaffolds.

PMID- 17518663
TI  - The effect of synovial fluid from injured knee joints on in vitro chondrogenesis.
AB  - Various in vivo and in vitro studies suggest that joint homeostasis may have a
      crucial effect on the quality of regeneration tissue resulting from cartilage
      tissue engineering techniques. The goal of the current study was to evaluate the
      effect of synovial fluid (SF) from injured knee joints on in vitro
      chondrogenesis. Chondrocytes were isolated from a healthy human femoral condyle
      (post-mortem) and expanded in monolayer for 2 passages. Subsequently, the
      chondrocytes were redifferentiated for 14 days on collagencoated filters,
      cultured either in the presence or absence of 10% SF. SF was obtained from 12
      injured human knee joints. After 14 days of culture, SF supplementation resulted
      in a significant downregulation of final proteoglycan (PG) content (7.3 +/- 1.8
      mg versus 15.6 +/- 1.3 mg; p = 0.0001), PG content normalized to DNA (0.7 +/- 0.5
      mg/microg versus 3.0 +/- 0.6 mg/microg; p < 0.05), relative collagen type II mRNA
      levels normalized to GAPDH mRNA levels (0.2 +/- 0.3 versus 7.0 +/- 5.6; p <
      0.001), and differentiation index (collagen type II/I mRNA ratio; 0.1 +/- 0.2
      versus 6.0 +/- 2.9; p < 0.001) as compared to control culture conditions.
      Additionally, SF-supplemented media resulted in significantly increased
      cellularity, as reflected by DNA content, compared with control media (1,369 +/-
      683 microg versus 514 +/- 72 microg; p < 0.0001). Morphology, and collagen type
      I, X, and aggrecan mRNA levels were not significantly affected. In conclusion,
      this study demonstrates that SF from injured human knee joints significantly
      affects in vitro chondrogenesis and therefore may provide a viable target for
      future improvement of ACT by refinement of culture techniques, patient selection,
      or pretreatment of affected joints to restore joint homeostasis.

PMID- 17518664
TI  - Elevated hepatocyte-specific functions in fetal rat hepatocytes co-cultured with
      adult rat hepatocytes.
AB  - Fetal hepatocytes (FHEPs) are a potential source of highly proliferative
      transplantable cells but express low levels of liver-specific functions. We
      hypothesized that the microenvironment of adult hepatocytes (AHEPs) may
      upregulate these functions. Primary FHEPs were seeded on top of collagen
      sandwiched AHEPs directly or separated by a porous transwell membrane insert. In
      direct co-cultures, albumin (ALB) secretion, urea synthesis, and cytochrome P450
      (CytP450) activity were all approximately 2 times as high as the sum of the
      corresponding monocultures. Using a transwell porous insert led to similar
      results, suggesting a major role for soluble factors. When AHEPs and FHEPs were
      separated after co-culture, they both initially showed significantly higher ALB
      secretion than control monocultures, whereas urea synthesis was significantly
      lower for the FHEPs only. Functions of previously co-cultured FHEPs normalized
      over the course of a week, but AHEP function remained high even after separation.
      In conclusion, co-culturing AHEPs with FHEPs increases expression of liver
      specific functions in both cell types. The effect on FHEPs, but not AHEPs, was
      reversible. Unraveling the underlying mechanisms and optimizing this phenomenon
      will be useful in making fetal liver cells a potential cell source for hepatic
      tissue-engineering applications.

PMID- 17518665
TI  - Matrix alteration and not residual sodium dodecyl sulfate cytotoxicity affects
      the cellular repopulation of a decellularized matrix.
AB  - It has been suggested that residual cytotoxic sodium dodecyl sulfate (SDS) is
      responsible for the low levels of cell in-growth observed in SDS decellularized
      tissues. To determine whether this is the case, we used 2 washing methods to
      remove residual SDS and extensive biochemical, mechanical, and structural
      analyses to determine the effects of SDS-based decellularization on porcine
      anterior cruciate ligament (ACL) tissue and its propensity for cellular
      repopulation. The level of residual SDS in decellularized tissue was reduced
      using 2 different washing techniques (pH = 9 buffer, 75% ethanol). After washing
      in pH = 9 or 75% ethanol, residual SDS concentrations in decellularized tissues
      were found to be approximately 8 and 23 times less than reported SDS cytotoxic
      levels, respectively. It was found that SDS treatment significantly reduced
      glycosaminoglycan levels, increased collagen crimp amplitude and periodicity, and
      increased susceptibility of collagen to degradation by the gelatinase enzyme
      trypsin. The level of repopulation and viability of autologous ACL fibroblasts in
      the decellularized tissue after 28 days of culture were found to be the same
      regardless of the washing technique and resulting level of residual SDS in the
      tissue. This strongly indicates that alterations in tissue matrix biochemistry or
      structure from SDS treatment and not residual SDS cytotoxicity are responsible
      for the low cell re-population observed in SDS decellularized tissues.

PMID- 17518666
TI  - A comparison of tissue-engineered hyaluronic acid dermal matrices in a human
      wound model.
AB  - The derivatives of hyaluronic acid (hyaluronan) have been extensively studied in
      the field of tissue engineering. Several forms of the material are available
      (benzyl esters of hyaluronic acid, HYAFF), with differing degradation profiles.
      This study compared 2 such products used for dermal regeneration (HYAFF p80 and
      HYAFF p100, the partial and total benzyl ester of hyaluronan, respectively), in a
      human model. In a prospective, randomized, controlled trial, 20 tattoos were
      tangentially excised and 1 of 2 hyaluronic acid-derived dermal matrices were
      applied to the wound bed. The partial ester was changed after 1 week and the
      total ester was kept for 2 weeks. After 2 weeks, cultured epidermal autograft was
      applied using the Laserskin method. Wounds were subsequently assessed by several
      modalities and by such features as rate of epithelialization, wound contraction,
      and histologic and immunohistologic appearances. Subtle differences were seen
      between the 2 groups, indicating that the total ester, which showed better
      clinical performance, could be used, especially in burns. This has the advantage
      of a single application for a 2-week period, rather than the comparison material,
      a partial ester, which requires weekly changing and degrades faster. Further, the
      method of epidermal grafting with a dermal substitute shows excellent results and
      adds to the armory for the treatment of both chronic and acute wounds.

PMID- 17518667
TI  - Tissue Engineering: The Next Generation. Proceedings of a workshop, May 2-4,
      2005, Cambridge, Massachusetts, USA.

PMID- 17518668
TI  - Tissue engineering: the next generation.

PMID- 17518669
TI  - Tissue engineering and developmental biology: going biomimetic.
AB  - This article contains the collective views expressed at the first session of the
      workshop "Tissue Engineering--The Next Generation," which was devoted to the
      interactions between developmental biology and tissue engineering. Donald Ingber
      discussed the chasms between developmental biology and tissue engineering from
      the perspective of a cell biologist who has had interest in tissue engineering
      since its early days. Van C. Mow shared a historical perspective on the
      development of tissue engineering as one of the first engineers involved in the
      field. David Butler offered an assessment of functional tissue engineering, a new
      area he helped establish and promote. Laura Niklason discussed how to be more
      effective in developing cellular therapies for large numbers of patients. Johnny
      Huard described his approach to tissue engineering, based on the use of muscle
      derived cells. Jeremy Mao focused on cell homing and cell density in the context
      of native development and relevance to tissue engineering. Ioannis Yannas
      proposed a set of "rules" in organ regeneration. Collectively, the faculty
      expressed a remarkable level of enthusiasm for bridging the gaps between
      developmental biology and tissue engineering and offered new ideas on how to
      facilitate the interaction between the two fields.

PMID- 17518670
TI  - Advanced tools for tissue engineering: scaffolds, bioreactors, and signaling.
AB  - This article contains the collective views expressed at the second session of the
      workshop "Tissue Engineering--The Next Generation,'' which was devoted to the
      tools of tissue engineering: scaffolds, bioreactors, and molecular and physical
      signaling. Lisa E. Freed and Farshid Guilak discussed the integrated use of
      scaffolds and bioreactors as tools to accelerate and control tissue regeneration,
      in the context of engineering mechanically functional cartilage and cardiac
      muscle. Edward Guo focused on the opportunities that tissue engineering generates
      for studies of mechanobiology and on the need for tissue engineers to learn about
      mechanical forces during tissue and organ genesis. Martha L. Gray focused on the
      potential of biomedical imaging for noninvasive monitoring of engineered tissues
      and on the opportunities biomedical imaging can generate for the development of
      new markers. Robert Tranquillo reviewed the approach to tissue engineering of a
      spectrum of avascular habitually loaded tissues- blood vessels, heart valves,
      ligaments, tendons, cartilage, and skin. Jeffrey W. Holmes offered the
      perspective of a "reverse paradigm''--the use of tissue constructs in
      quantitative studies of cell-matrix interactions, cell mechanics, matrix
      mechanics, and mechanobiology. Milica Radisic discussed biomimetic design of
      tissue-engineering systems, on the example of synchronously contractile cardiac
      muscle. Michael V. Sefton proposed a new, simple approach to the vascularization
      of engineered tissues. This session stressed the need for advanced scaffolds,
      bioreactors, and imaging technologies and offered many enlightening examples on
      how these advanced tools can be utilized for functional tissue engineering and
      basic research in medicine and biology.

PMID- 17518672
TI  - Translation from research to applications.
AB  - The article summarizes the collective views expressed at the fourth session of
      the workshop Tissue Engineering--the Next Generation, which was devoted to the
      translation of results of tissue engineering research into applications. Ernst
      Hunziker described the paradigm of a dual translational approach, and argued that
      tissue engineering should be guided by the dimensions and physiological setting
      of the bodily compartment to be repaired. Myron Spector discussed collagen
      glycosaminoglycan (GAG) scaffolds for musculoskeletal tissue engineering.
      Jeanette Libera focused on the biological and clinical aspects of cartilage
      tissue engineering, and described a completely autologous procedure for
      engineering cartilage using the patient's own chondrocytes and blood serum.
      Arthur Gertzman reviewed the applications of allograft tissues in orthopedic
      surgery, and outlined the potential of allograft tissues as models for biological
      and medical studies. Savio Woo discussed a list of functional tissue engineering
      approaches designed to restore the biochemical and biomechanical properties of
      injured ligaments and tendons to be closer to that of the normal tissues.
      Specific examples of using biological scaffolds that have chemoattractants as
      well as growth factors with unique contact guidance properties to improve their
      healing process were shown. Anthony Ratcliffe discussed the translation of the
      results of research into products that are profitable and meet regulatory
      requirements. Michael Lysaght challenged the proposition that commercial and
      clinical failures of early tissue engineering products demonstrate a need for
      more focus on basic research. Arthur Coury described the evolution of tissue
      engineering products based on the example of Genzyme, and how various definitions
      of success and failure can affect perceptions and policies relative to the status
      and advancement of the field of tissue engineering.

PMID- 17518673
TI  - Effects of growth factors on extracellular matrix production by vocal fold
      fibroblasts in 3-dimensional culture.
AB  - Culturing cells in 3-dimensional (3D) systems is important in tissue engineering
      and in fundamental studies of cellular mechanisms that are sensitive or specific
      to the 3D environment. To guide the engineering of artificial vocal fold lamina
      propria tissue, we developed 3D cultures containing human vocal fold fibroblasts
      (hVFFs) dispersed in a synthetic peptide hydrogel matrix. Growth factors were
      added to the culture to examine their influence on extracellular matrix (ECM)
      synthesis, cell proliferation, and matrix contraction. The hVFF-hydrogel
      constructs were treated with transforming growth factor-beta 1 (TGF-beta1), basic
      fibroblast growth factor (bFGF), or hepatocyte growth factor (HGF), and the
      culture was maintained for 21 days. TGF-beta1 induced matrix contraction and
      enhanced collagen and sulfated glycosaminoglycan production, bFGF effectively
      increased cell proliferation, and HGF stimulated synthesis of hyaluronic acid and
      elastin with less collagen accumulation than other conditions. Of the growth
      factors tested, HGF appears to be most useful for stimulating essential tissue
      components for restoring vocal fold pliability. The results also suggest that
      multiple growth factors might be employed sequentially or in combination to
      program the makeup of cell-hydrogel constructs for vocal fold tissue repair.

PMID- 17518674
TI  - Cell-assisted lipotransfer: supportive use of human adipose-derived cells for
      soft tissue augmentation with lipoinjection.
AB  - Injective transfer of autologous aspirated fat is a popular option for soft
      tissue augmentation, but several issues require attention, including
      unpredictability and a low survival rate due to partial necrosis. In this study,
      histologic features and yield of adipose-derived stromal (stem) cells (ASCs) were
      compared between human aspirated fat and excised whole fat. Aspirated fat
      contained fewer large vascular structures, and ASC yield was lower in aspirated
      fat. Aspirated fat was transplanted subcutaneously into severe combined
      immunodeficiency mice with (cell-assisted lipotransfer; CAL) or without (non-CAL)
      vascular stromal fractions containing ASCs isolated from adipose tissue. The CAL
      fat survived better (35% larger on average) than non-CAL fat, and
      microvasculature was detected more prominently in CAL fat, especially in the
      outer layers. DiI-labeled vascular stromal fraction cells were found between
      adipocytes and in the connective tissue in CAL fat, and some of these cells were
      immunopositive for von Willebrand factor, suggesting differentiation into
      vascular endothelial cells. Another experiment that used vascular stromal
      fractions taken from green fluorescent protein rats also suggested that ASCs
      differentiated into vascular endothelial cells and contributed to neoangiogenesis
      in the acute phase of transplantation. These findings may partly explain why
      transplanted aspirated fat does not survive well and suggest clinical potential
      of the CAL method for soft tissue augmentation.

PMID- 17518671
TI  - Engineering complex tissues.
AB  - This article summarizes the views expressed at the third session of the workshop
      "Tissue Engineering--The Next Generation," which was devoted to the engineering
      of complex tissue structures. Antonios Mikos described the engineering of complex
      oral and craniofacial tissues as a "guided interplay" between biomaterial
      scaffolds, growth factors, and local cell populations toward the restoration of
      the original architecture and function of complex tissues. Susan Herring,
      reviewing osteogenesis and vasculogenesis, explained that the vascular
      arrangement precedes and dictates the architecture of the new bone, and proposed
      that engineering of osseous tissues might benefit from preconstruction of an
      appropriate vasculature. Jennifer Elisseeff explored the formation of complex
      tissue structures based on the example of stratified cartilage engineered using
      stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a
      problem critical for biological fixation of tendons and ligaments, and the
      development of a new generation of fixation devices. Rita Kandel discussed the
      challenges related to the re-creation of the cartilage-bone interface, in the
      context of tissue engineered joint repair. Frederick Schoen emphasized, in the
      context of heart valve engineering, the need for including the requirements
      derived from "adult biology" of tissue remodeling and establishing reliable early
      predictors of success or failure of tissue engineered implants. Mehmet Toner
      presented a review of biopreservation techniques and stressed that a new
      breakthrough in this field may be necessary to meet all the needs of tissue
      engineering. David Mooney described systems providing temporal and spatial
      regulation of growth factor availability, which may find utility in virtually all
      tissue engineering and regeneration applications, including directed in vitro and
      in vivo vascularization of tissues. Anthony Atala offered a clinician's
      perspective for functional tissue regeneration, and discussed new biomaterials
      that can be used to develop new regenerative technologies.

PMID- 17518675
TI  - Repair and regeneration of the abdominal wall musculofascial defect using silk
      fibroin-chitosan blend.
AB  - Reconstructive surgery with synthetic or biological materials is commonly
      performed to repair abdominal wall musculofascial defects that result from
      ventral hernias. A study was conducted to investigate the feasibility of using
      silk fibroin and chitosan blend (SFCS) scaffolds for ventral hernia repair in
      guinea pigs. We compared SFCS with biodegradable human acellular dermal matrix
      (HADM) and nonbiodegradable polypropylene mesh by implanting each to repair an
      incisionally created ventral hernia in the abdominal wall using an inlay
      technique. At 4 weeks, both HADM and SFCS underwent remodeling by host tissue,
      but polypropylene mesh resulted in extensive bowel adhesions and scarring.
      Abdominal wall repairs with SFCS showed tissue remodeling in all 3 dimensions,
      with seamless integration at the interface with adjacent native tissue. The SFCS
      repair sites remained intact, and their mechanical strength was similar to that
      of the native abdominal wall despite greater degradation and remodeling of SFCS
      than of HADM. The deposition of new extracellular matrix consisting of collagen
      and ground substance, uniform vascularization, and cellular infiltration in SFCS
      repair sites contributed to the increase in mechanical strength of the
      regenerated tissue. Thus, SFCS is a potentially useful material for clinical
      abdominal wall reconstruction, since it becomes remodeled and integrated into the
      surrounding abdominal wall and maintains adequate tensile strength.

PMID- 17518676
TI  - Quantitative analysis of radiation-induced DNA break repair in a cultured oral
      mucosal model.
AB  - Oral mucositis is a major side effect of radiation therapy. Development of
      strategies for reduction of this problem calls for quantitative models. The goal
      of the present study was to test the feasibility of detecting double-strand
      breaks (DSBs) and DSB repair proteins upon radiation of mucosa in a 3-dimensional
      culture system using morphology and immunohistochemistry. Human oral
      keratinocytes and fibroblasts were seeded onto and into an acellular dermal
      carrier to produce a cultured mucosal substitute (CMS). CMSs were gamma
      irradiated with 0, 2, and 12 Gy. One group received 4 Gy through 2 Gy fractions
      with a 24-h interval. Radiation-induced damage was quantified using hematoxylin
      and eosin (H&E). DSBs and DSB repair proteins were visualized and quantified
      using antibodies against P53 binding protein 1 (53BP1), MRE11, and RAD51. As in
      cell culture, CMSs showed intranuclear loci of damage and repair, mostly in the
      proliferative basal cell layers. Maximum percentages of damaged basal layer
      keratinocytes were 54.8% using H&E (12 Gy) up to 78.9% (12 Gy) for 53BP1. This
      study shows the feasibility of DNA repair markers to quantify radiation damage.
      This is an important step forward in the study of mucositis and the development
      of treatment and prevention strategies, proving once more the power and clinical
      importance of tissue engineering.

PMID- 17518677
TI  - Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem
      cells in an injectable, in situ, cross-linked synthetic extracellular matrix.
AB  - A co-cross-linked synthetic extracellular matrix (sECM) composed of chemically
      modified hyaluronic acid and gelatin was used as a cell delivery vehicle for
      osteochondral defect repair in a rabbit model. A full-thickness defect was
      created in the patellar groove of the femoral articular cartilage in each of 2
      rabbit joints, and 4 experimental groups were assigned (12 rabbits/group):
      untreated control, autologous mesenchymal stem cells (MSCs) only, sECM only, and
      MSCs + sECM. The sECM hydrogels were allowed to cross-link in the defect in situ.
      Rabbits were sacrificed at 4, 8, and 12 weeks post-surgery, and cartilage repair
      was evaluated and scored. In the controls, defects were filled with fibrous
      tissue. In the MSC-only group, hyaline-like cartilage filled the peripheral area
      of the defect, but the center was filled with fibrous tissue. In the sECM-only
      group, hyaline cartilage with zonal architecture filled the defect at 12 weeks,
      but an interface between repaired and adjacent host cartilage was evident. In the
      MSCs + sECM group, defects were completely filled with elastic, firm, translucent
      cartilage at 12 weeks and showed superior integration of the repair tissue with
      the normal cartilage. The sECM delivers and retains MSCs, and the injectable cell
      seeded sECM could be delivered arthroscopically in the clinic.

PMID- 17518678
TI  - Effect of scaffold design on bone morphology in vitro.
AB  - Silk fibroin is an important polymer for scaffold designs, forming biocompatible
      and mechanically robust biomaterials for bone, cartilage, and ligament tissue
      engineering. In the present work, 3D biomaterial matrices were fabricated from
      silk fibroin with controlled pore diameter and pore interconnectivity, and
      utilized to engineer bone starting from human mesenchymal stem cells (hMSC).
      Osteogenic differentiation of hMSC seeded on these scaffolds resulted in
      extensive mineralization, alkaline phosphatase activity, and the formation of
      interconnected trabecular- or cortical-like mineralized networks as a function of
      the scaffold design utilized; allowing mineralized features of the tissue
      engineered bone to be dictated by the scaffold features used initially in the
      cell culture process. This approach to scaffold predictors of tissue structure
      expands the window of applications for silk fibroin-based biomaterials into the
      realm of directing the formation of complex tissue architecture. As a result of
      slow degradation inherent to silk fibroin, scaffolds preserved their initial
      morphology and provided a stable template during the mineralization phase of stem
      cells progressing through osteogenic differentiation and new extracellular matrix
      formation. The slow degradation feature also facilitated transport throughout the
      3D scaffolds to foster improved homogeneity of new tissue, avoiding regions with
      decreased cellular density. The ability to direct bone morphology via scaffold
      design suggests new options in the use of biodegradable scaffolds to control in
      vitro engineered bone tissue outcomes.

PMID- 17518679
TI  - Tissue-engineered vascular grafts as in vitro blood vessel mimics for the
      evaluation of endothelialization of intravascular devices.
AB  - The accelerating use of minimally invasive procedures for the treatment of
      cardiovascular disease, and the commensurate development of intravascular devices
      such as stents, has lead to a high demand for preclinical assessment techniques.
      A 3-dimensional in vitro blood vessel mimic (BVM) would be ideal for device
      testing before animal or clinical studies. This is possible based on current
      capabilities for the creation of tissue-engineered vascular grafts (TEVGs). Using
      an established method of pressure-sodding human endothelial cells onto a polymer
      scaffold, a BVM was created in an in vitro bioreactor system under flow. Scanning
      electron microscopy and immunohistochemistry verified a cellular lining and
      revealed a luminal monolayer of endothelial cells. After BVM development, bare
      metal stents were deployed. Stented and unstented BVMs were evaluated using
      fluorescent nuclear staining and optical coherence tomography (OCT). En face and
      cross-sectional evaluation of bisbenzimide-stained nuclei revealed cellular
      coverage of the stent surfaces. Cross-sectional evaluation using OCT also
      illustrated a cellular layer developing over the stent struts. These data support
      the use of TEVGs as in vitro BVMs for pre-clinical evaluation of the endothelial
      cell response to stents and endovascular devices.

PMID- 17518680
TI  - Identification and reduction of cryoinjury in endothelial cells: a first step
      toward establishing a cell bank for vascular tissue engineering.
AB  - We analyzed a cryopreservation protocol which improves long-term storage of
      endothelial cells (EC) for tissue engineering purposes. Human umbilical vein EC
      were frozen in a high-potassium solution containing 10% dimethyl sulfoxide using
      3 different cooling rates. After a storage time in liquid nitrogen of 1, 4, or 12
      months, samples were thawed and compared to fresh cells in terms of growth rates,
      anti-inflammatory, and anticoagulant functions. Independent of cooling rate and
      storage time, the retrieval after cryopreservation ranged between 60% and 80%.
      However, viability of the cells cryopreserved at 10 degrees C/min decreased
      significantly from 78 +/- 5% to 64 +/-3% with storage. Storage time of 4 months
      resulted in a decreased cell multiplication factor over 4 and 12 days in culture.
      The lag phases returned to normal in the next passage. Thawed cells showed
      increased metabolic activity, reduced expression of thrombomodulin, and unchanged
      basal expression of adhesion molecules. However, the tumor necrosis factor
      induced expression of adhesion molecules was significantly increased after long
      term storage. This effect was partially compensated after expansion of the cells,
      whereas the prostacyclin release increased. Expansion of cryopreserved/thawed EC
      resulted in highly proliferative cells with antithrombotic properties and a
      capacity for inflammatory reactions, which makes them suitable for vascular
      tissue engineering.

PMID- 17518681
TI  - Kinetics of in vivo bone deposition by bone marrow stromal cells into porous
      calcium phosphate scaffolds: an X-ray computed microtomography study.
AB  - In a typical bone tissue engineering application, osteogenic cells are harvested
      and seeded on a three-dimensional (3D) synthetic scaffold that acts as guide and
      stimulus for tissue growth, creating a tissue engineering construct or living
      biocomposite. Despite the large number of performed experiments in different
      laboratories, information on the kinetics of bone growth into the scaffolds is
      still scarce. Highly porous hydroxyapatite scaffolds were investigated before the
      implantation and after they were seeded with in vitro expanded bone marrow
      stromal cells (BMSC) and implanted for 8, 16, or 24 weeks in immunodeficient
      mice. Synchrotron x-ray computed microtomography (microCT) was used for
      qualitative and quantitative 3D characterization of the scaffold material and 3D
      evaluation of tissue engineered bone growth kinetics after in vivo implantation.
      Experiments were performed taking advantage of a dedicated set up at the European
      Synchrotron Radiation Facility (ESRF, Grenoble, France), which allowed
      quantitative imaging at a spatial resolution of about 5 microm. A peculiarity of
      these experiments was the fact that at first the data were obtained on the
      different pure scaffolds, then the same scaffolds were seeded by BMSC, implanted,
      and brought again to ESRF for investigating the formation of new bone. The volume
      fraction, average thickness, and distribution of the newly formed bone were
      evaluated as a function of the implantation time. New bone thickness increased
      from week 8 to week 16, but deposition of new bone was arrested from week 16 to
      week 24. Instead, mineralization of the newly deposited bone matrix continued up
      to week 24.

PMID- 17518682
TI  - Osteogenic differentiation of human mesenchymal stem cells in collagen matrices:
      effect of uniaxial cyclic tensile strain on bone morphogenetic protein (BMP-2)
      mRNA expression.
AB  - Human mesenchymal stem cells (hMSCs) differentiate down an osteogenic pathway
      with appropriate mechanical and/or chemical stimuli. This study describes the
      successful culture of hMSCs in 3D collagen matrices under mechanical strain. Bone
      marrow-derived hMSCs were seeded in linear 3D type I collagen matrices and
      subjected to 0%, 10%, or 12% uniaxial cyclic tensile strain at 1 Hz for 4 h/day
      for 7 or 14 days. Cell viability studies indicated that hMSCs remained viable
      throughout the culture period irrespective of the applied strain level. Real-time
      RT-PCR studies indicated a significant increase in BMP-2 mRNA expression levels
      in hMSCs strained at 10% compared to the same day unstrained controls after both
      7 and 14 days. An increase in BMP-2 was also observed in hMSCs subjected to 12%
      strain, but the increase was significant only in the 14-day sample. This is the
      first report of the culture of bone marrow-derived hMSCs in 3D collagen matrices
      under cyclic strain, and the first demonstration that strain alone can induce
      osteogenic differentiation without the addition of osteogenic supplements.
      Induction of bone differentiation in 3D culture is a critical step in the
      creation of bioengineered bone constructs.

PMID- 17518683
TI  - Autospecies and post-myocardial infarction sera enhance the viability,
      proliferation, and maturation of 3D cardiac cell culture.
AB  - The limited ability of cardiac muscle to regenerate after an extensive myocardial
      infarction (MI) and the scarcity of cardiac donors have fueled the field of
      cardiac tissue engineering as a potential therapeutic approach to enhance cardiac
      function in post-MI patients. We are exploring the ex vivo bioengineering of
      cardiac muscle tissue by seeding isolated cardiac cells within alginate scaffolds
      and supplementing the culture with "smart" media. The hypothesis investigated
      herein is that sera derived from autospecies and from post-MI animals contain
      agents that might induce cell proliferation, survival, and maturation in vitro.
      The results of the metabolic activity of the neonatal cardiac cell constructs
      (6.4-51x10(6) cells/cm(3)), as measured by MTT viability assay, indicated a
      significant advantage (p < 0.05) to the constructs supplemented with serum from
      normal and post-MI adult rats compared to fetal calf serum (FCS) supplementation.
      H&E staining and alpha-sarcomeric actin immunofluorescence staining revealed
      thick viable cardiac cell clusters (150-300 microm), with abundant 3D
      architecture in the cardiac cell constructs supplemented with post-MI and normal
      adult rat serum. The number of cells positively immunostained with Ki-67, a cell
      proliferation marker, was significantly higher in post-MI adult rat serum
      supplemented cultures compared to negative results in the FCS-supplemented
      culture. The results presented in this study indicate that media supplemented
      with post-MI adult rat serum and normal adult rat serum compared to FCS have a
      significant advantage in the regeneration of injured cardiac tissue.

PMID- 17518684
TI  - Hepatic differentiation potential of commercially available human mesenchymal
      stem cells.
AB  - The ready availability and low immunogenicity of commercially available
      mesenchymal stem cells (MSC) render them a potential cell source for the
      development of therapeutic products. With cell source a major bottleneck in
      hepatic tissue engineering, we investigated whether commercially available human
      MSC (hMSC) can transdifferentiate into the hepatic lineage. Based on previous
      studies that find rapid gain of hepatic genes in bone marrow-derived stem cells
      cocultured with liver tissue, we used a similar approach to drive hepatic
      differentiation by coculturing the hMSC with rat livers treated or untreated with
      gadolinium chloride (GdCl(3)). After a 24-hour coculture period with liver tissue
      injured by GdCl(3) in a Transwell configuration, approximately 34% of the cells
      differentiated into albumin-expressing cells. Cocultured cells were subsequently
      maintained with growth factors to complete the hepatic differentiation.
      Cocultured cells expressed more hepatic gene markers, and had higher metabolic
      functions and P450 activity than cells that were only differentiated with growth
      factors. In conclusion, commercially available hMSC do show hepatic
      differentiation potential, and a liver microenvironment in culture can provide
      potent cues to accelerate and deepen the differentiation. The ability to generate
      hepatocyte-like cells from a commercially available cell source would find
      interesting applications in liver tissue engineering.

PMID- 17518685
TI  - Glucose concentration and medium volume influence cell viability and
      glycosaminoglycan synthesis in chondrocyte-seeded alginate constructs.
AB  - Increasing the thickness of tissue-engineered cartilage is associated with loss
      of chondrocyte viability and biosynthetic activity at the tissue center.
      Exceptionally high volumes of culture medium, however, can maintain cellularity
      and glycosaminoglycan synthesis throughout 4-mm-thick constructs. We hypothesized
      that glucose supplementation could replicate the augmentation of tissue formation
      achieved by medium volume. Chondrocyte-alginate constructs (40x10(6) cells/mL)
      were cultured for 14 days in 0.4-6.4 mL/10(-6) cells of either low- (5.1 mM) or
      high- (20.4 mM) glucose medium. Glucose was critical to chondrocyte viability,
      and glucose uptake increased significantly (P < .001) with both medium volume and
      glucose supplementation. After 14 days, constructs cultured in 0.4 mL/10(-6)
      cells of low-glucose medium had a mass of 172 +/- 6.1 mg and glycosaminoglycan
      (GAG) content of 0.32 +/- 0.03 mg (mean +/- standard deviation). A 4-fold
      increase in medium volume increased the final construct mass by 44% and GAG
      content by 207%. An equivalent increase in glucose supply in the absence of
      volume change increased these parameters by just 10% and 73%, respectively. A
      similar trend was observed from 0.8 to 3.2 mL/10(-6) cells, when maximal values
      of construct GAG content and mass were obtained. Therefore, medium volume remains
      an important consideration for the optimal culture of tissue-engineered
      cartilage.

PMID- 17518686
TI  - Development of controlled matrix heterogeneity on a triphasic scaffold for
      orthopedic interface tissue engineering.
AB  - Biological fixation of orthopedic soft tissue grafts to bone poses a significant
      clinical challenge. The clinical success of soft tissue-based grafts for anterior
      cruciate ligament (ACL) reconstruction is limited by the lack of functional graft
      integration with subchondral bone. Soft tissues such as the ACL connect to
      subchondral bone via a complex interface whereby three distinct tissue regions
      (ligament, fibrocartilage, and bone) work in concert to facilitate load transfer
      from soft to hard tissue while minimizing stress concentration at the interface.
      Although a fibrovascular tissue forms at the graft-to-bone interface following
      surgery, this tissue is nonphysiologic and represents a weak link between the
      graft and bone. We propose that the re-establishment of the native multi-tissue
      interface is essential for biological graft fixation. In vivo observations and
      our in vitro monolayer co-culture results suggest that osteoblast-fibroblast
      interaction is important for interface regeneration. This study focuses on the
      design of a triphasic scaffold system mimicking the multi-tissue organization of
      the native ACL-to-bone interface and the evaluation of osteoblast-fibroblast
      interactions during three-dimensional co-culture on the triphasic scaffold. We
      found that the triphasic scaffold supported cell proliferation, migration and
      phenotypic matrix production while maintaining distinct cellular regions and
      phase-specific extracellular matrix deposition over time. This triphasic scaffold
      is designed to guide the eventual reestablishment of an anatomically oriented and
      mechanically functional fibrocartilage interfacial region directly on biological
      and synthetic soft tissue grafts. The results of this study demonstrate the
      feasibility of multi-tissue regeneration on a single scaffold, and the potential
      of interface tissue engineering to enable the biological fixation of soft tissue
      grafts to bone.

PMID- 17518687
TI  - Evaluation of silicon dioxide-based coating enriched with bioactive peptides
      mapped on human vitronectin and fibronectin: in vitro and in vivo assays.
AB  - A wide range of biochemical signals promoting cell functions (adhesion,
      migration, proliferation, and differentiation) and thereby improving the
      osseointegration process are currently investigated. Unfortunately, their
      application for the production of bioactive implantable devices is often hampered
      by their insolubility; instability; and limited availability of a large amount of
      inexpensive, high-purity samples. An attractive alternative is the use of short
      peptides carrying the minimum active sequence of the natural factors. Synthetic
      peptides mapped on fibronectin and vitronectin have been demonstrated to enhance
      cell adhesion both to polystyrene and acellular bone matrix; in particular, a
      nonapeptide sequence from human vitronectin works via an osteoblast-specific
      adhesion mechanism. In this study, we incorporated these peptides into a sol-gel
      silica dressing applied to coat sand-blasted and acid-attacked titanium samples;
      measured the kinetic of peptide release; and used titanium disks, coated with a
      peptide-enriched film, as substrates to determine the peptide concentration that
      maximizes cell adhesion in vitro. We also evaluated in vivo the capacity of the
      vitronectin-derived peptide to improve osteogenic activity: histologic analysis
      revealed markedly improved osteogenic activity around peptide-enriched samples.
      This article also discusses the role of surface characteristics and the
      importance of bioactive peptides.

PMID- 17518688
TI  - Effects of glutamine, glucose, and oxygen concentration on the metabolism and
      proliferation of rabbit adipose-derived stem cells.
AB  - The use of adipose-derived stem cells (ASCs) for tissue engineering involves
      exposing them to metabolically adverse conditions. This study examined the
      metabolism, proliferation, and viability of ASCs under various oxygen, glucose,
      and glutamine concentrations to determine how these cells respond to such
      environments. ASCs were cultured in each of 8 media preparations containing 4.8
      or 21.5 mM glucose, and 0, 2, 4, or 6 mM glutamine. The ASCs were cultured under
      normoxic (20% O(2)) and hypoxic (0.1% O(2)) conditions. Conditioned media were
      collected and assayed for glucose, glutamine, lactate, pyruvate, and glutamate.
      Cell proliferation and cell death were measured after 5 days of culture. ASCs
      remained metabolically active under all culture conditions; however, their
      proliferation rate was significantly reduced in the absence of glutamine. Hypoxia
      resulted in increased cell death. ASCs are a viable source of stem cells for
      tissue engineering purposes, although substantial challenges remain. These cells
      are able to survive in environments with limited oxygen and glutamine and thus
      may be able to survive brief periods of limited nutrient transport after
      implantation.

PMID- 17518689
TI  - Three-dimensional flow perfusion culture system for stem cell proliferation
      inside the critical-size beta-tricalcium phosphate scaffold.
AB  - A 3-dimensional flow perfusion system has been created in our laboratory to
      provide continuous and homogeneous nutrient supply inside the critical-size beta
      tricalcium phosphate (beta-TCP) scaffold and permit cell proliferation during
      long-term incubation. The critical-size porous cylindrical scaffold (14 mm in
      diameter, 30 mm in length) with a central tunnel was impregnated with sheep
      mesenchymal stem cells. In the flow perfusion group, the hybrid scaffolds were
      continuously perfused with complete alpha-minimum essential medium via a
      peristaltic pump for 7, 14, and 28 days. In the static culture group, the hybrid
      composites were immersed in the medium without perfusion for 14 and 28 days. The
      daily glucose consumption was much higher in the flow perfusion group than in the
      static group (p < 0.001). In the flow perfusion group, glucose consumption
      increased dramatically in the first 14 days, and the increase slowed in the last
      14 days. In the static group, the increase occurred only in the first 14 days.
      Cell viability via MTT colorimetry increased with time, which coincided with the
      results of glucose consumption. Histological study showed that the cells
      proliferated through the whole scaffolds under the flow perfusion culture. While
      under the static culture, the cells survived and proliferated only inside the
      first to third rows of the macropores under the scaffold surface. The cell
      quantity increased with time under flow perfusion culture. The results suggest
      that flow perfusion culture is superior to static culture for mesenchymal stem
      cell proliferation in the critical-size porous scaffold. This perfusion culture
      system permits a constant nutrition supply into the center of a large-scale
      scaffold for at least 4 weeks. Determination of D-glucose in the culture medium
      is a noninvasive way to survey cell proliferation in this system.

PMID- 17518690
TI  - Unphysiologically high magnesium concentrations support chondrocyte proliferation
      and redifferentiation.
AB  - The effect of unphysiologically high extracellular magnesium concentrations on
      chondrocytes, induced by the supplementation of magnesium sulfate, was studied
      using a 3-phase tissue engineering model. The experiments showed that chondrocyte
      proliferation and redifferentiation, on the gene and protein expression level,
      are enhanced. A negative influence was found during chondrogenesis where an
      inhibition of extracellular matrix formation was observed. In addition, a direct
      impact on chondrocyte metabolism, elevated magnesium concentrations also affected
      growth factor effectiveness by consecutive influences during chondrogenesis. All
      observations were dosage dependent. The results of this study indicate that
      magnesium may be a useful tool for cartilage tissue engineering.

PMID- 17518691
TI  - Polyesteramide-derived nonwovens as innovative degradable matrices support
      preadipocyte adhesion, proliferation, and differentiation.
AB  - Extended soft tissue defects resulting from injuries or tumor resections are
      still an unresolved problem in plastic and reconstructive surgery because
      adequate reconstruction is difficult. Immature adipogenic precursor cells, called
      preadipocytes, which are located between mature adipocytes in adipose tissue,
      represent a powerful tool for soft tissue engineering because of their ability to
      proliferate and differentiate into adipose tissue after transplantation. In
      previous studies, we compared preadipocyte-loaded hyaluronan or collagen
      biomaterials and their applicability for adipose tissue engineering. Our findings
      demonstrated successful de novo formation of adipose tissue in vivo but pore size
      and stiffness were limiting factors not allowing for sufficient cell distribution
      in the construct. This study presents a nonwoven made of novel bioabsorbable co
      poly(ester amide) based on e-caprolactam, adipic acid, and 1,4-butanediol in an
      innovative 3-dimensional architecture. The material was formed into nonwovens by
      textile manufacturing using an aerodynamic web formation process and a needle
      felting technique. Carriers were seeded with human preadipocytes and examined for
      cellular proliferation and differentiation. In addition, methods of preparing
      scaffolds for optimal cell interaction were evaluated. Our findings show that
      polyesteramide-derived nonwovens allow good adherence, proliferation, and
      differentiation of preadipocytes. These results are promising guidance toward an
      optimally designed scaffold for in vivo use.

PMID- 17518693
TI  - Mathematical models for the proliferation of neural stem/progenitor cells in
      clonogenic culture.
AB  - Neurospheres are free-floating heterogeneous spheroid structures maintained in
      culture and have been used for in vitro expansion of neural stem/progenitor
      cells. But the growth characteristics and proliferation kinetics of cell
      population in neurospheres are poorly understood. Using clonogenic culture and
      immunocytochemistry, we observed the growth dynamics of cell populations in
      neurospheres and identified key parameters relating to the growth dynamics of
      cells in neurospheres, including the fraction of dividing cells, cell cycle
      duration, time delay of first division, and survival rate of cells. Based on
      these parameters, we established two mathematical models that describe kinetic
      features of neural stem/progenitor cells under clonogenic conditions. These
      models provide a powerful tool to explain and predict the experimental outcome
      and clarify the cell growth characteristics of neural stem/progenitor cells.

PMID- 17518694
TI  - Oxidative stress of neural, hematopoietic, and stem cells: protection by natural
      compounds.
AB  - During natural aging, adult stem cells are known to have a reduced restorative
      capacity and are more vulnerable to oxidative stress resulting in a reduced
      ability of the body to heal itself. We report here that the proprietary natural
      product formulation, NT020, previously found to promote proliferation of human
      hematopoietic stem cells, reduced oxidative stress-induced apoptosis of murine
      neurons and microglial cells in vitro. Furthermore, when taken orally for 2
      weeks, cultured bone marrow stem cells from these mice exhibited a dose-related
      reduction of oxidative stress-induced apoptosis. This preclinical study
      demonstrates that NT020 can act to promote healing via an interaction with stem
      cell populations and forms the basis of conducting a clinical trial to determine
      if NT020 exhibits similar health promoting effects in humans when used as a
      dietary supplement.

PMID- 17518695
TI  - Oxidative DNA damage repair and parp 1 and parp 2 expression in Epstein-Barr
      virus-immortalized B lymphocyte cells from young subjects, old subjects, and
      centenarians.
AB  - Oxidative DNA damage has been implicated in the aging process and in some of its
      features such as telomere shortening and replicative senescence. Poly(ADP
      ribosyl)ation is involved in many molecular and cellular processes, including DNA
      damage detection and repair, chromatin modification, transcription, and cell
      death pathways. We decided to examine the behavior of poly(ADP-ribosyl)ation in
      centenarians, i.e., those subjects who represent the best example of longevity
      having reached a very advanced age avoiding the main age-associated diseases. In
      this study we investigated the relationship between DNA repair capacity and
      poly(ADP-ribose) polymerase activity in Epstein-Barr virus-immortalized B
      lymphocyte cell lines from subjects of three different groups of age, including
      centenarians. Our data show that cells from centenarians have characteristics
      typical of cells from young people both in their capability of priming the
      mechanism of repair after H(2)O(2) sublethal oxidative damage and in poly(ADP
      ribosyl)ation capacity, while in cells from old subjects these phenomena are
      delayed or decreased. Moreover, cells from old subjects show a constitutive
      expression level of both parp 1 and parp 2 genes reduced by a half, together with
      a reduced presence of modified PARP 1 and other poly(ADP-ribosyl)ated chromatin
      proteins in comparison to cells from young subjects and centenarians. Our data
      support the hypothesis that this epigenetic modification is an important
      regulator of the aging process in humans and it appears to be rather preserved in
      healthy centenarians, the best example of successful aging.

PMID- 17518696
TI  - Long-term low-calorie low-protein vegan diet and endurance exercise are
      associated with low cardiometabolic risk.
AB  - BACKGROUND: Western diets, which typically contain large amounts of energy-dense
      processed foods, together with a sedentary lifestyle are associated with
      increased cardiometabolic risk. We evaluated the long-term effects of consuming a
      low-calorie low-protein vegan diet or performing regular endurance exercise on
      cardiometabolic risk factors. METHODS: In this cross-sectional study,
      cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had
      been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean
      age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners
      consuming Western diets, and 21 age- and gender-matched sedentary subjects,
      consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein
      vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2))
      groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p <
      0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C
      reactive protein, blood pressure (BP), and carotid artery intima-media thickness
      were lower in the low-calorie low-protein vegan diet and runner groups than in
      the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower
      in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg)
      than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western
      diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly
      associated with sodium intake and inversely associated with potassium and fiber
      intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan
      diet or regular endurance exercise training is associated with low
      cardiometabolic risk. Moreover, our data suggest that specific components of a
      low-calorie low-protein vegan diet provide additional beneficial effects on blood
      pressure.

PMID- 17518697
TI  - SENS: an engineer's point of view on feasibility and bioethics dialogue.

PMID- 17518699
TI  - The olive constituent oleuropein exhibits proteasome stimulatory properties in
      vitro and confers life span extension of human embryonic fibroblasts.
AB  - Normal human fibroblasts undergo replicative senescence due to both genetic and
      environmental factors. Senescence and aging can be further accelerated by
      exposure of cells to a variety of oxidative agents that contribute among other
      effects to the accumulation of damaged proteins. The proteasome, a multicatalytic
      nonlysosomal protease, has impaired function during aging, while its increased
      expression delays senescence in human fibroblasts. The aim of this study was to
      identify natural compounds that enhance proteasome activity and exhibit antiaging
      properties. We demonstrate that oleuropein, the major constituent of Olea europea
      leaf extract, olive oil and olives, enhances the proteasome activities in vitro
      stronger than other known chemical activators, possibly through conformational
      changes of the proteasome. Moreover, continuous treatment of early passage human
      embryonic fibroblasts with oleuropein decreases the intracellular levels of
      reactive oxygen species (ROS), reduces the amount of oxidized proteins through
      increased proteasome-mediated degradation rates and retains proteasome function
      during replicative senescence. Importantly, oleuropein-treated cultures exhibit a
      delay in the appearance of senescence morphology and their life span is extended
      by approximately 15%. In summary, these data demonstrate the beneficial effect of
      oleuropein on human fibroblasts undergoing replicative senescence and provide new
      insights towards enhancement of cellular antioxidant mechanisms by natural
      compounds that can be easily up-taken through normal diet.

PMID- 17518698
TI  - Examination of cognitive function during six months of calorie restriction:
      results of a randomized controlled trial.
AB  - BACKGROUND: Calorie restriction increases longevity in many organisms, and
      calorie restriction or its mimetic might increase longevity in humans. It is
      unclear if calorie restriction/dieting contributes to cognitive impairment.
      During this randomized controlled trial, the effect of 6 months of calorie
      restriction on cognitive functioning was tested. METHODS: Participants (n = 48)
      were randomized to one of four groups: (1) control (weight maintenance), (2)
      calorie restriction (CR; 25% restriction), (3) CR plus structured exercise (CR +
      EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), or
      (4) low-calorie diet (LCD; 890 kcal/d diet until 15% weight loss, followed by
      weight maintenance). Cognitive tests (verbal memory, visual memory,
      attention/concentration) were conducted at baseline and months 3 and 6. Mixed
      linear models tested if cognitive function changed significantly from baseline to
      months 3 and 6, and if this change differed by group. Correlation analysis was
      used to determine if average daily energy deficit (quantified from change in body
      energy stores) was associated with change in cognitive test performance for the
      three dieting groups combined. RESULTS: No consistent pattern of verbal memory,
      visual retention/memory, or attention/concentration deficits emerged during the
      trial. Daily energy deficit was not significantly associated with change in
      cognitive test performance. CONCLUSIONS: This randomized controlled trial
      suggests that calorie restriction/dieting was not associated with a consistent
      pattern of cognitive impairment. These conclusions must be interpreted in the
      context of study limitations, namely small sample size and limited statistical
      power. Previous reports of cognitive impairment might reflect sampling biases or
      information processing biases.

PMID- 17518700
TI  - Living and all-time longevity record-holders over the age of 110.

PMID- 17518701
TI  - Microsatellite instability and compromised mismatch repair gene expression during
      in vitro passaging of monoclonal human T lymphocytes.
AB  - An age-related accumulation of DNA damage caused by increased insult and/or
      decreased repair, could contribute to impaired cellular function. DNA mismatch
      repair (MMR), the main postreplicative correction pathway, can be monitored by
      assessing microsatellite instability and has been reported to decrease with age.
      Here, we analyzed the involvement of the MMR system in the accumulation of
      genetic damage in a cultured monoclonal human T lymphocyte model. We correlated
      microsatellite instability (MSI) and MMR gene expression, and replicative
      senescence of CD4+ clones derived from young, old and centenarian individuals or
      from CD34+ precursors. Cells were analyzed for MSI at five loci (CD4, VWA, Fes,
      D2S123, and BAT26), for the methylation status of MLH1 and MSH2 gene promoters,
      and for the expression of the MMR genes MSH2, MSH6, MSH3, MLH1, PMS2, and PMS1.
      MSI increased with increasing culture passages, particularly in the CD34+
      progenitor-derived clones, but also in those from adult T cells. MSI and MMR gene
      expression were found to correlate, mostly due to a reduced expression of the
      components of MutL heterodimers, pointing to a role of MMR in the acquisition of
      DNA damage with in vitro aging.

PMID- 17518702
TI  - Reconstruction of a hard connective tissue utilizing a pressed silk sheet and
      type-I collagen as the scaffold for fibroblasts.
AB  - A pressed silk sheet is a new biomaterial composed of a network of numerous
      cocoon filaments and having excellent mechanical strength and shape stability
      compared to a cotton-gauze sheet. To reconstruct a hard connective tissue using
      the silk sheet and type-I collagen as the scaffold for fibroblasts, three
      different three-dimensional floating culture systems were designed. "On sheet"
      system: fibroblasts were seeded on the silk sheet coated with collagen and the
      cell-attached sheet was cultured. "In gel" system: fibroblasts and the silk sheet
      were co-embedded in a collagen gel and the gel was cultured. "On vitrigel"
      system: fibroblasts were seeded on both sides of a collagen vitrigel involving
      the silk sheet and the vitrigel was cultured. The fibroblasts in all culture
      systems grew and formed disk-shaped connective tissue models involving the silk
      sheet by 14 days of culture. The "on sheet" and "on vitrigel" models retained a
      maximum elastic load of about 23 kgf and an ultimate tensile load of about 3.6
      kgf, which were almost the same as for the individual silk sheet. However, the
      "in gel" system showed a low value for the tensile load. Cell damage following
      application of mechanical stress was lowest in the "on vitrigel" system. These
      data demonstrated the advantage of the "on vitrigel" system in reconstructing
      hard connective tissues. Such a novel culture method would contribute to a
      regenerative medicine for the failure of ligaments, tendons, and other connective
      tissues.

PMID- 17518703
TI  - Chemical and physical regulation of stem cells and progenitor cells: potential
      for cardiovascular tissue engineering.
AB  - The field of cardiovascular tissue engineering has experienced tremendous
      advances in the past several decades, but the clinical reality of engineered
      heart tissue and vascular conduits remains immature. Stem cells and progenitor
      cells are promising cell sources for engineering functional cardiovascular
      tissues. To realize the therapeutic potential of stem cells and progenitor cells,
      we need to understand how microenvironmental cues modulate and guide stem cell
      differentiation and organization. This review describes the current understanding
      of the chemical and physical regulation of embryonic and adult stem cells for
      potential applications in cardiovascular repair, focusing on cardiac therapies
      after myocardial infarction and the engineering of vascular conduits.

PMID- 17518704
TI  - Expanded adipose-derived stem cells suppress mixed lymphocyte reaction by
      secretion of prostaglandin E2.
AB  - Multipotent mesenchymal stem cells (MSCs) in adult tissue are known to be less
      immunogenic and immunosuppressive. Previous study showed that primary cultures of
      human adipose-derived stem cells (ADSCs) shared their immunomodulatory properties
      with other MSCs. However, whether passaged human ADSCs can retain their
      immunomodulatory effect after in vitro expansion remains unknown. In addition,
      the mechanism of ADSC-mediated immunomodulatory effect remains to be elucidated.
      This study aimed to investigate these issues by using passaged human ADSCs as an
      in vitro study model. Flow cytometry showed that passaged ADSCs expressed human
      leukocyte antigen (HLA) class I but not class II molecules, which could be
      induced to express to a high level with interferon-gamma (IFN-gamma) treatment.
      The study found that passaged ADSCs could not elicit lymphocyte proliferation
      after co-culturing with them, even after IFN-gamma treatment. In addition, either
      IFN-gamma-treated or non-treated ADSCs could inhibit phytohemagglutinin (PHA)
      stimulated lymphocyte proliferation. Moreover, passaged ADSCs could serve as the
      third-party cells to inhibited two-way mixed lymphocyte reaction (MLR). Further
      study using a transwell system also showed that this type of immunosuppressive
      effect was not cell-cell contact dependent. In defining possible soluble factors,
      we found that passaged ADSCs significantly increased their secretion of
      prostaglandin E2 (PGE2), but not transforming growth factor-beta (TGF-beta) and
      hepatocyte growth factor (HGF), when they were co-cultured with MLR. Furthermore,
      the result demonstrated that only PGE2 production inhibitor indomethacine, but
      not TGF-beta- and HGF-neutralizing antibodies, could significantly counteract
      ADSC-mediated suppression on allogeneic lymphocyte proliferation. These results
      indicated that in vitro expanded ADSCs retain low immunogenicity and
      immunosuppressive effect, and PGE2 might be the major soluble factor involved in
      the in vitro inhibition of allogeneic lymphocyte reaction.

PMID- 17518705
TI  - Photochemically cross-linked collagen gels as three-dimensional scaffolds for
      tissue engineering.
AB  - Collagen gels have many favorable attributes for tissue engineering, but the gels
      undergo dramatic contraction when cells are added because of the weak noncovalent
      bonds that form during spontaneous gelation. We hypothesized that photochemically
      cross-linking collagen gels would make suitable scaffolds for tissue engineering
      with favorable cell viability and minimal gel contraction. Rose Bengal and
      riboflavin were chosen as candidate photo-initiators for gel cross-linking using
      532- and 458-nm-light wavelengths, respectively. Chondrocyte viability was
      measured after initial gelation for several concentrations of initiators. Cell
      viability and gel contraction were then measured using chondrocytes and
      fibroblasts over 7 days of culture. Rose Bengal used at concentrations necessary
      for gelation resulted in little or no cell viability. Short-term viability
      results showed that 0.25- or 0.5-mM concentrations of riboflavin, and 40 s of
      illumination permitted more than 90% cell viability. Using riboflavin
      concentrations of 0.25 or 0.5 mM, long-term chondrocyte viability was 113.1 +/-
      11.6% and 25.4 +/- 2.7%, respectively, at day 7. Although non-cross-linked
      chondrocyte constructs contracted to 59.9 +/- 11.8% of their original diameter
      and fibroblasts contracted to 24.9 +/- 5.0% of their original diameter by day 7,
      the cross-linked constructs retained 88.8 +/- 7.4% and 85.5 +/- 5.0% of the
      original diameter, respectively. In conclusion, by photochemically cross-linking
      collagen gels using riboflavin and visible light, stable gel scaffolds with
      favorable cell survival can be produced.

PMID- 17518706
TI  - Characterization and inhibition of fibrin hydrogel-degrading enzymes during
      development of tissue engineering scaffolds.
AB  - The goal of articular cartilage tissue engineering is to provide cartilaginous
      constructs to replace abnormal cartilage. We have evaluated the chondroprogenitor
      clonal cell line RCJ3.1C5.18 (C5.18) as a model to guide the development of
      appropriate scaffolds for tissue engineering. Rapid degradation of fibrin
      hydrogels was observed after encapsulation of C5.18 cells. The enzymes
      responsible for this fibrin gel breakdown were characterized to control their
      activity and regulate gel stability. Western blotting, confirming zymography,
      revealed bands due to matrix metalloproteinases (MMP-2, MMP-3) that are secreted
      concomitantly with fibrin hydrogels breakdown. High plasmin activity was detected
      in conditioned media during hydrogel breakdown but not in the confluent cells
      before encapsulation. Reverse transcriptase polymerase chain reaction indicated
      the expression of MMP-2, -3, and -9 and plasminogen in the cells. MMP-9 was 100
      times higher at day 1, whereas MMP-2 started to increase and reached its maximum
      level by day 7. Aprotinin, a known serine protease inhibitor, and galardin
      (GM6001), a potent MMP inhibitor, in combination or separately, prevented the
      breakdown of fibrin-C5.18 hydrogels, whereas only the combination of both
      promoted the accumulation of extracellular matrix. These findings suggest that
      plasmin and MMPs contribute independently to fibrin hydrogel breakdown, but that
      either enzyme can achieve extracellular matrix breakdown.

PMID- 17518707
TI  - Refining retinoic acid stimulation for osteogenic differentiation of murine
      adipose-derived adult stromal cells.
AB  - Murine adipose-derived adult stromal cells (ADAS) seeded onto appropriate
      scaffolds and pre-incubated with retinoic acid have been shown to generate in
      vivo bone rapidly. Prompt resorption ensues, however, as a result of
      osteoclastogenesis, likely secondary to retinoic acid carryover. In this study,
      we determined the effects of abbreviated retinoic acid exposure on ADAS
      osteogenic differentiation. Histological staining and gene expression analysis
      revealed that longer retinoic acid exposure resulted in better in vitro bone
      differentiation. However, significant osteogenesis was observed in ADAS after
      just 15 days of retinoic acid supplementation, suggesting that continual culture
      with retinoic acid is unnecessary for initiation of the osteogenic program. This
      was confirmed using ADAS pre-incubated in monolayer with an abbreviated 15 days
      of retinoic acid exposure before implantation into critical-sized calvarial
      defects. Similar rates of regeneration were observed between ADAS exposed to for
      15 days or for a full 25-day course of retinoic acid before defect repair.
      Furthermore, by limiting retinoic acid exposure to ADAS in monolayer without
      scaffold, accelerated bone formation was observed without concomitant
      osteoclastic resorption. These data suggest that skeletal regeneration may be
      improved by modulating retinoic acid exposure before implantation, markedly
      accelerating the repair of bone defects using ADAS.

PMID- 17518708
TI  - Tissue engineering the mandibular condyle.
AB  - Tissue engineering provides the revolutionary possibility for curing
      temporomandibular joint (TMJ) disorders. Although characterization of the
      mandibular condyle has been extensively studied, tissue engineering of the
      mandibular condyle is still in an inchoate stage. The purpose of this review is
      to provide a summary of advances relevant to tissue engineering of mandibular
      cartilage and bone, and to serve as a reference for future research in this
      field. A concise anatomical overview of the mandibular condyle is provided, and
      the structure and function of the mandibular condyle are reviewed, including the
      cell types, extracellular matrix (ECM) composition, and biomechanical properties.
      Collagens and proteoglycans are distributed heterogeneously (topographically and
      zonally). The complexity of collagen types (including types I, II, III, and X)
      and cell types (including fibroblast-like cells, mesenchymal cells, and
      differentiated chondrocytes) indicates that mandibular cartilage is an
      intermediate between fibrocartilage and hyaline cartilage. The fibrocartilaginous
      fibrous zone at the surface is separated from hyaline-like mature and
      hypertrophic zones below by a thin and highly cellular proliferative zone.
      Mechanically, the mandibular condylar cartilage is anisotropic under tension
      (stiffer anteroposteriorly) and heterogeneous under compression (anterior region
      stiffer than posterior). Tissue engineering of mandibular condylar cartilage and
      bone is reviewed, consisting of cell culture, growth factors, scaffolds, and
      bioreactors. Ideal engineered constructs for mandibular condyle regeneration must
      involve two distinct yet integrated stratified layers in a single osteochondral
      construct to meet the different demands for the regeneration of cartilage and
      bone tissues. We conclude this review with a brief discussion of tissue
      engineering strategies, along with future directions for tissue engineering the
      mandibular condyle.

PMID- 17518709
TI  - Effects of serial passaging on the adipogenic and osteogenic differentiation
      potential of adipose-derived human mesenchymal stem cells.
AB  - Adipose-derived human mesenchymal stem cells (hMSCs) will be more valuable for
      tissue engineering applications if they can be extensively subcultured without
      loss of phenotype and multilineage differentiation ability. This study examined
      the effects of serial passaging on growth rate, gene expression, and
      differentiation potential of adipose-derived hMSCs. Differentiation was assessed
      by analyzing changes in messenger RNA (mRNA) expression of osteogenic and
      adipogenic marker genes and by determining production of calcium deposits and
      lipid vacuoles. Cells cultured in osteogenic medium for 2 weeks upregulated
      expression of alkaline phosphatase mRNA relative to cells in growth medium, and
      deposited calcium. Calcium deposition decreased in cells from passages 4 to 6 but
      returned to levels near or above those of primary cells by passage 10. Cells
      cultured in adipogenic medium upregulated expression of lipoprotein lipase and
      peroxisome proliferator activated receptor-gamma mRNA relative to cells in growth
      medium, and formed lipid vacuoles at all passages. By passage 8, however, cells
      in adipogenic medium also deposited calcium. Growth rate was stable through
      passage 5, then decreased. The results of this study indicate that adipose
      derived hMSCs are capable of both adipogenic and osteogenic differentiation
      through 10 passages (34 population doublings) but that osteogenic differentiation
      may start to dominate at later passages.

PMID- 17518711
TI  - Production of a novel fibroblast-populated platelet matrix cocultured with
      keratinocytes.
AB  - We have developed a new method for the production of a dermal matrix equivalent.
      Human platelets were used to dilute human fibroblasts. The platelet mix was
      placed in a cell culture well. Addition of 200 microL of a thrombin solution
      caused gel formation. Gels were overlaid with standard Iscove's growth medium
      supplemented with 10% fetal bovine serum, insulin, and N-2-hydroxyethylpiperazine
      N'-2-ethanesulfonic acid buffer. Medium was exchanged regularly. Keratinocytes
      were plated on top of selected gels and elevated to the air-liquid interface. The
      gels were harvested weekly, fixed, cut, and stained with hematoxylin and eosin
      stains and immunostains for collagens I, III, and IV and cytokeratins. Digital
      image analysis was used to quantitate collagen production. Growth factors,
      including transforming growth factor-beta (TGF-beta), platelet-derived growth
      factor, and vitamin C were added. Staining identified fibroblasts within the gels
      with a surrounding fibrous matrix. Immunostaining for cytokeratin identified
      keratinocytes on the gel surface. Immunostaining revealed the fibrous matrix to
      be composed of collagen I and III and some collagen IV. Digital image analysis
      demonstrated that greater TGF-beta concentration resulted in greater collagen
      production. These differences were statistically significant. With development of
      this construct, a viable dermal/epidermal replacement may be possible. TGF-beta
      enhances collagen production by fibroblasts in this matrix.

PMID- 17518710
TI  - Differential effects on messenger ribonucleic acid expression by bone marrow
      derived human mesenchymal stem cells seeded in agarose constructs due to ramped
      and steady applications of cyclic hydrostatic pressure.
AB  - This study investigated the differential effects of ramped and steady
      applications of cyclic hydrostatic pressure (CHP) on chondrogenic differentiation
      of bone marrow-derived human mesenchymal stem cells (hMSCs) in 3-dimensional
      culture in the absence of transforming growth factor-beta (TGF-beta). A custom
      hydrostatic pressure system was designed and manufactured. hMSCs were seeded in
      agarose and exposed to steady (7.5 MPa) or ramped (1 MPa to 7.5 MPa over a 14-day
      period) CHP for 4 h/d at f = 1 Hz for 14 days. Real-time reverse transcriptase
      polymerase chain reaction analysis was performed on days 0, 4, 9, and 14 to
      determine changes in messenger ribonucleic acid (mRNA) expression levels of Sox9,
      aggrecan, collagen I, and collagen II. Collagen II and aggrecan mRNA expression
      remained unchanged. Collagen I increased at day 4 in CHP specimens before
      decreasing to levels at or below same-day unloaded controls at days 9 and 14. On
      average, ramped and steady regimens of CHP increased Sox9, with the largest
      upregulation occurring at day 4 in response to steady pressure. These findings
      indicate that hydrostatic pressure may induce chondrogenesis in hMSC-seeded
      agarose constructs without TGF-beta, and that hMSCs are capable of withstanding
      high initial pressures that may initiate chondrogenesis faster than lower
      pressures.

PMID- 17518712
TI  - Alginate encapsulation impacts the insulin-like growth factor-I system of
      monolayer-expanded equine articular chondrocytes and cell response to interleukin
      1beta.
AB  - Alginate hydrogel culture has been shown to reestablish chondrocytic phenotype
      following monolayer expansion; however, previous studies have not adequately
      addressed how culture conditions affect the signaling systems responsible for
      chondrocyte metabolic activity. Here we investigate whether chondrocyte culture
      history influences the insulin-like growth factor-I (IGF-I) signaling system and
      its regulation by interleukin-1 (IL-1). Articular chondrocytes (ACs) from equine
      stifle joints were expanded by serial passage and were either encapsulated in
      alginate beads or maintained in monolayer culture for 10 days. Alginate-derived
      cells (ADCs) and monolayer-derived cells (MDCs) were then plated at high density,
      stimulated with IL-1beta (1 and 10 ng/mL) or IGF-I (50 ng/mL) for 48 h, and
      assayed for levels of type I IGF receptor (IGF-IR), IGF binding proteins
      (IGFBPs), and endogenously secreted IGF-I. Intermediate alginate culture yielded
      relatively low IGF-IR levels that increased in response to IL-1beta, whereas
      higher receptor levels on MDCs were reduced by cytokine. MDCs also secreted
      substantially more IGFBP-2, the predominant binding protein in conditioned media
      (CM), though IL-1beta suppressed levels for both cell populations. Concentrations
      of autocrine/paracrine IGF-I paralleled IGFBP-2 secretion. Disparate basal levels
      of IGF-IR and IGFBP-2, but not IGF-I, were attributed to relative transcript
      expression. Systemic differences coincided with varied effects of IL-1beta and
      IGF-I on cell growth and type I collagen expression. We conclude that culture
      strategy impacts the IGF-I signaling system of ACs, potentially altering their
      capacity to mediate cartilage repair. Consideration of hormonal regulators may be
      an essential element to improve chondrocyte culture protocols used in tissue
      engineering applications.

PMID- 17518713
TI  - Dynamics of the self-assembly of complex cellular aggregates on micromolded
      nonadhesive hydrogels.
AB  - The process by which cells self-assemble to form three-dimensional (3D)
      structures is central to morphogenesis and development of living tissues and
      hence is of growing interest to the field of tissue engineering. Using rapid
      prototyping technology we made micromolded nonadhesive hydrogels to study the
      dynamics of self-assembly in a low-shear environment with simple spherical
      geometries as well as more complex geometries such as a toroid. Aggregate size,
      shape, and composition were easily controlled; aggregates were easily retrieved;
      and the dynamics of the assembly process were readily observed by time-lapse
      microscopy. When two cell types, normal human fibroblasts (NHFs) and human
      umbilical vein endothelial cells (HUVECs), were seeded together, they self
      segregated into multilayered spherical microtissues with a core of NHFs enveloped
      by a layer of HUVECs. Surprisingly, when a single cell suspension of NHFs was
      added to 7-day-old HUVEC spheroids, the HUVEC spheroid reorganized such that NHFs
      occupied the center and HUVECs coated the outside, demonstrating that self
      assembly is not terminal and that spheroids are fluid structures that retain the
      ability to reassemble. We also showed that cells can self-assemble to form a
      complex toroid shape, and we observed several phenomena indicating that cellular
      contraction and tension play a significant role in the assembly process of
      complex shapes.

PMID- 17518714
TI  - Stimulation of peri-implant vascularization with bone marrow-derived progenitor
      cells: monitoring by in vivo EPR oximetry.
AB  - The poorly vascularized fibrous capsule that develops around implantable
      biomedical devices (for drug delivery, biosensors, etc.) severely limits their
      applications. We tested the hypotheses that co-implantation of bone marrow
      derived progenitor cells could stimulate the vascularization of implants. To
      assess the presence of functional peri-implant microvasculature, we developed a
      novel model of implanted device containing an oxygen (O(2))-sensing spin probe
      (detectable using electron paramagnetic resonance) placed inside a nanoporous
      filter-limited capsule. These devices were implanted subcutaneously in C57/Bl6
      mice alone, with the addition of a Matrigel plug in front of the filter, or with
      the addition of Matrigel containing equal proportions of c-kit(+) and stem cell
      antigen-1(+) bone marrow-derived cells. Implants partial pressure of O(2) (pO(2))
      were recorded non-invasively and periodically for up to 10 weeks. Tissue
      surrounding the implants was collected for immunohistochemistry. Initially, there
      were no differences in pO(2) between the experimental groups. After 3 weeks, the
      devices supplied with progenitor cells showed more than twice the O(2)
      concentrations as controls. This difference remained significant for 4 more weeks
      and then started to decrease slightly, still being 6 mmHg higher than in the
      controls at 10 weeks post-implantation. Collagen deposition was detected around
      the control implants, along with F4/80-positive macrophages and giant cells. In
      the plugs collected from the cell treatment group, we found an active process of
      adipogenesis, accompanied by neovascularization, and a highly vascularized
      adipose layer surrounding the implants. In conclusion, we successfully developed
      a cell therapy-type strategy to maintain vascularization around implanted devices
      using co-administration of bone marrow-derived progenitor cells, and we
      demonstrated a novel O(2)-sensing method to functionally monitor
      neovascularization in vivo.

PMID- 17518715
TI  - Mechanical stimulation increases collagen type I and collagen type III gene
      expression of stem cell-collagen sponge constructs for patellar tendon repair.
AB  - Our group has shown that mechanical stimulation increases the stiffness of stem
      cell-collagen sponge constructs at 14 days in culture and subsequent rabbit
      patellar tendon repairs at 12 weeks postsurgery. What remains unclear is which
      genes might be responsible for this increase in stiffness. Therefore, the
      objective of this study was to determine how a tensile stimulus affects the gene
      expression of stem cell-collagen sponge constructs used to repair rabbit central
      patellar tendon defects. Tissue-engineered constructs were created by seeding
      mesenchymal stem cells (MSCs) from 10 adult rabbits at 0.14 x 10(6)
      cells/construct in type I collagen sponges. Half of the constructs were
      mechanically stimulated once every 5 min for 8 h/d to a peak strain of 2.4% for 2
      weeks. The other half remained in an incubator without mechanical stimulation for
      2 weeks. After 14 days in culture, half of the stimulated and nonstimulated
      constructs were prepared to determine the expression of collagen type I, collagen
      type III, decorin, fibronectin, and glyceraldehyde-3-phosphate dehydrogenase
      genes using real-time quantitative reverse transcriptase polymerase chain
      reaction. The remaining constructs were mechanically tested to determine their
      mechanical properties. Two weeks of in vitro mechanical stimulation significantly
      increased collagen type I and collagen type III gene expression of the stem cell
      collagen sponge constructs. Stimulated constructs showed 3 and 4 times greater
      collagen type I (p = 0.0001) and collagen type III gene expression (p = 0.001)
      than nonstimulated controls. Stimulated constructs also had 2.5 times the linear
      stiffness and 4 times the linear modulus of nonstimulated constructs. However,
      mechanical stimulation did not significantly increase decorin or fibronectin gene
      expression (p = 0.2) after 14 days in culture. This study shows that mechanical
      stimulation of cell-sponge constructs produces similar increases in the
      expression of 2 structural genes, as well as linear stiffness and linear modulus.

PMID- 17518716
TI  - Efficient production of bioactive insulin from human epidermal keratinocytes and
      tissue-engineered skin substitutes: implications for treatment of diabetes.
AB  - Despite many years of research, daily insulin injections remain the gold standard
      for diabetes treatment. Gene therapy may provide an alternative strategy by
      imparting the ability to secrete insulin from an ectopic site. The epidermis is a
      self-renewing tissue that is easily accessible and can provide large numbers of
      autologous cells to generate insulin-secreting skin substitutes. Here we used a
      recombinant retrovirus to modify human epidermal keratinocytes with a gene
      encoding for human proinsulin containing the furin recognition sequences at the A
      C and B-C junctions. Keratinocytes were able to process proinsulin and secrete
      active insulin that promoted glucose uptake. Primary epidermal cells produced
      higher amounts of insulin than cell lines, suggesting that insulin secretion may
      depend on the physiological state of the producer cells. Modified cells
      maintained the ability to stratify into 3-dimensional skin equivalents that
      expressed insulin at the basal and suprabasal layers. Modifications at the furin
      recognition sites did not improve proinsulin processing, but a single amino acid
      substitution in the proinsulin B chain enhanced C-peptide secretion from cultured
      cells and bioengineered skin substitutes 10- and 28-fold, respectively. These
      results suggest that gene-modified bioengineered skin may provide an alternative
      means of insulin delivery for treatment of diabetes.

PMID- 17518717
TI  - Gene expression by fibroblasts seeded on small intestinal submucosa and subjected
      to cyclic stretching.
AB  - Extracellular matrix scaffolds derived from porcine small intestinal submucosa
      (SIS-ECM) have been shown to promote the formation of site-specific tissue in a
      number of preclinical animal studies. However, this constructive remodeling
      process requires that the scaffold be subjected to a site-specific mechanical
      environment. The specific quantitative effects of mechanical loading on the gene
      expression patterns of fibroblasts seeded on SIS-ECM are unknown and yet very
      important in the tissue remodeling process. The objective of the present study
      was to evaluate the expression of collagen type I (Col I), collagen type III (Col
      III), smooth muscle actin (SMA), tenascin-C (TN-C), matrix metalloprotease-2 (MMP
      2), matrix metalloprotease-9 (MMP-9), transforming growth factor-beta1 (TGF
      beta1), and transforming growth factor-beta3 (TGF-beta3) by fibroblasts subjected
      to various magnitudes (0%, 5%, 10%, and 15%) and frequencies (0.1 Hz, 0.3 Hz, and
      0.5 Hz) of stretch. A new cyclic-stretching tissue culture (CSTC) system was
      developed. This system consists of eight independently controlled culture
      chambers that can be operated in a sterile incubator. Each chamber includes a
      load cell so that the load in each scaffold can be monitored. It was found that
      different stretching regimens led to complex and distinctive patterns of gene
      expression by fibroblasts seeded onto SIS-ECM. In general, the fibroblasts
      increased expression of Col I up to 5-fold and decreased that of Col III with
      increased frequency of stretch. In addition, the fibroblasts exhibited a
      contractile phenotype with increased expression of SMA, TN-C, and TGF-beta1.
      These findings support the concept that the mechanical environment of a
      remodeling ECM scaffold may have substantial effects on the behavior of cells
      within the scaffold and contribute to the site-specific tissue remodeling that
      has been observed in in vivo studies.

PMID- 17518718
TI  - Tissue-engineering approach to regenerating the intervertebral disc.
AB  - In today's world there is an ever increasing incidence of low back pain, which is
      generally attributed to degeneration of the intervertebral disc (IVD) in those in
      their second or third decade of life. The most prevalent treatment modalities
      involve conservative methods (physical therapy and medications) or surgical
      fusion of the upper and lower vertebral bodies. In the last 10 years, there has
      been a surge of interest in applying tissue-engineering principles to treat
      spinal problems associated with the IVD. Tissue engineering provides many
      promising advantages to treating disc degeneration; it adopts a more biological
      and reparative approach, whereby the main goal is to restore the properties of
      the disc to its pre-degenerative state. This review outlines the physiology of
      the IVD and the etiology of disc degeneration. Much of the research carried out
      in the field of tissue engineering is based on three predominant constituents:
      cells, scaffolds, and signals. Thus, specific attention is given to these
      constituents and their potential use in repairing the IVD. Some of the
      significant challenges involved in IVD tissue engineering are also identified,
      and a brief discussion regarding possible future areas of research follows.

PMID- 17518719
TI  - Controlled release of stromal cell-derived factor-1 alpha in situ increases c
      kit+ cell homing to the infarcted heart.
AB  - Stromal-derived factor 1alpha (SDF-1alpha) is a key stem cell homing factor that
      is crucial for mobilization of stem cells from bone marrow to peripheral blood
      and subsequent engraftment to the tissue of diseased organs. It has been reported
      that SDF-1alpha is transiently over-expressed in ischemic myocardium. Therefore,
      there may be a limited time window after acute myocardial infarction (AMI) during
      which stem cells are recruited to injured myocardium for repair. This study aimed
      at investigating whether controlled release of SDF-1alpha via a novel conjugated
      poly(ethylene glycol) (PEG) (PEGylated) fibrin patch at the infarct site would
      increase the rate of stem cell recruitment and offer potential therapeutic
      benefits. Recombinant mouse SDF-1alpha was covalently bound to the PEGylated
      fibrinogen as evidenced by immunoprecipitation and western blotting. The
      PEGylated fibrinogen, bound with recombinant mouse SDF-1alpha, was mixed with
      thrombin to form the PEGylated fibrin patch. The release kinetics of SDF-1alpha
      were detected in vitro using enzyme-linked immunosorbent assay. Using a mouse AMI
      model produced by a ligature on the left anterior descending coronary artery, a
      PEGylated fibrin patch bound with SDF-1alpha (100 ng) was placed on the surface
      of the infarct area of the left ventricle. Infarct size, left ventricular (LV)
      function, and the percentage of sca-1(+)/c-kit(+) cells within the infarct area
      were measured at days 7, 14, and 28 after AMI. In vitro results showed that SDF
      1alpha was successfully bound to the PEGylated fibrin patch and can be released
      from the patch constantly for up to 10 days. Two weeks after infarction, the
      myocardial recruitment of c-kit(+) cells was significantly higher in the group
      treated with the SDF-1alpha PEGylated fibrin patch (n = 9) than in the AMI
      control group (n = 10) (p < 0.05; 11.20 +/- 1.71% vs. 4.22 +/- 0.96%,
      respectively). At day 28 post-AMI, unlike the control group, the group with the
      SDF-1alpha-releasing patch maintained stable release of SDF-1alpha concurrent
      with additional stem cell homing. Moreover, LV function was significantly better
      than in the control group. These data demonstrate that the PEGylated fibrin patch
      based SDF-1alpha delivery can improve the rate of c-kit(+) cell homing and
      improve LV function in hearts with postinfarction LV remodeling.

PMID- 17518720
TI  - Osterix induces osteogenic gene expression but not differentiation in primary
      human fetal mesenchymal stem cells.
AB  - The transcription factor osterix (Osx) is a key regulator of osteoblast
      differentiation and induces bone formation in embryonic but not adult stem cells.
      We investigated the effect of up-regulating Osx on an intermediate stem cell
      type, first trimester fetal mesenchymal stem cells (MSCs), which are more
      expandable than adult MSCs. Human fetal (hf ) MSCs were transduced with a
      lentiviral vector encoding human Osx. In undifferentiating MSCs cultures, forced
      expression of Osx stimulated osteopontin and alkaline phosphatase expression.
      However, Osx did not up-regulate osteocalcin, a late marker of osteoblast
      differentiation or result in extracellular calcium crystals, indicating that Osx
      does not directly mediate terminal differentiation in primary hfMSCs. To
      understand the downstream effects of Osx expression in primary hfMSCs, we next
      investigated the regulatory relationship between Osx, and the transcription
      factors Dlx5, Runx2, and Msx2. Osx induced Dlx5 but did not affect Runx2 and
      Msx2, whereas stealth ribonucleic acid interference of Osx inhibited Dlx5 without
      affecting expression of Runx2 and Msx2. In conclusion, Osx regulates osteogenic
      gene expression in hfMSCs but is insufficient to induce terminal osteogenic
      differentiation.

PMID- 17518721
TI  - Starch-based microparticles as vehicles for the delivery of active platelet
      derived growth factor.
AB  - In a previous work, we described the use of starch-based microparticles as
      vehicles for the controlled release of corticosteroids. The goal of the present
      work is to evaluate the potential of these microparticles to incorporate and
      release platelet-derived growth factor (PDGF). The loading efficiency and release
      profile were evaluated, and PDGF was incorporated into and released from the
      matrix of starch-based microparticles. The release profile shows rapid release of
      PDGF in the first 24 h, after which there was a slow but constant release for up
      to 8 weeks. The maintenance of the PDGF biological activity after incorporation
      and release was evaluated by its mitogenic effect over osteoblastic cells, and it
      was shown to be comparable to that of PDGF supplemented to the culture medium.
      This proves that the incorporation and release did not affect the biological
      activity of the growth factor (GF). The results clearly demonstrate that starch
      based microparticles are suitable vehicles for the incorporation and release of
      GFs. When combined with previous results, these materials also suggest their
      ability to enhance the regenerating potential of tissue engineering hybrid
      constructs.

PMID- 17518722
TI  - A comparison of human umbilical cord matrix stem cells and temporomandibular
      joint condylar chondrocytes for tissue engineering temporomandibular joint
      condylar cartilage.
AB  - The temporomandibular joint (TMJ) presents many problems in modern
      musculoskeletal medicine. Patients who suffer from TMJ disorders often experience
      a major loss in quality of life due to the debilitating effects that TMJ
      disorders can have on everyday activities. Cartilage tissue engineering can lead
      to replacement tissues that could be used to treat TMJ disorders. In this study,
      a spinner flask was used for a period of 6 days to seed polyglycolic acid (PGA)
      scaffolds with either TMJ condylar chondrocytes or mesenchymal-like stem cells
      derived from human umbilical cord matrix (HUCM). Samples were then statically
      cultured for 4 weeks either in growth medium containing chondrogenic factors or
      in control medium. Immunohistochemical staining of HUCM constructs after 4 weeks
      revealed a strong presence of collagen I and minute amounts of collagen II,
      whereas TMJ constructs revealed little collagen I and no collagen II. The HUCM
      constructs were shown to contain more GAGs than the TMJ constructs quantitatively
      at week 0 and histologically at week 4. Moreover, the cellularity of HUCM
      constructs was 55% higher at week 0 and nearly twice as high after 4 weeks,
      despite being seeded at the same density. The increased level of biosynthesis and
      higher cellularity of HUCM constructs clearly demonstrates that the HUCM stem
      cells outperformed the TMJ condylar cartilage cells under the prescribed
      conditions. HUCM stem cells may therefore be an attractive alternative to
      condylar cartilage cells for TMJ tissue engineering applications. Further, given
      the availability and ease of obtaining HUCM stem cells, these findings may have
      far-reaching implications, leading to novel developments in both craniofacial and
      orthopaedic tissue replacement therapies.

PMID- 17518723
TI  - Time-related analysis of metabolic liver functions, cellular morphology, and gene
      expression of hepatocytes cultured in the bioartificial liver of the Academic
      Medical Center in Amsterdam (AMC-BAL).
AB  - A comprehensive understanding of the mechanisms that underlie hepatic
      differentiation inside a bioartificial liver (BAL) device is obtained when
      functional, histological, and gene expression analyses can be combined. We
      therefore developed a novel cell-sampling technique that enabled us to analyze
      adherent hepatocytes inside a BAL device during a 5-day culture period, without
      the necessity of terminating the culture. Biochemical data showed that hepatocyte
      specific functions were relatively stable, despite an increase in glycolytic
      activity. Quantitative reverse transcriptase polymerase chain reaction analysis
      of hepatic genes cytochrome p450 3A29, albumin, glutamine synthetase, alpha-1
      antitrypsin, and carbamoyl-phosphate synthetase, but also de-differentiation
      marker pi-class glutathione S transferase showed stable messenger ribonucleic
      acid (mRNA) levels from day 1 to 5. In contrast, mRNA levels of alpha
      fetoprotein, pro- and anti-apoptotic genes Bax-alpha and Bcl-X(L), metabolic
      genes lactate dehydrogenase and uncoupling protein 2, and cytoskeleton genes
      alpha- and beta-tubulin and beta-actin increased in 5 days. Histological analysis
      revealed viable tissue-like structures with adaptation to the in vitro
      environment. We conclude that hepatocytes show a tendency for de-differentiation
      shortly after seeding but thereafter remain acceptably differentiated during 5
      days of culture. Furthermore, partly impaired mitochondrial function is
      suggestive for local hypoxic regions and may trigger the observed metabolic
      changes. Anti-apoptotic activity seems to balance pro-apoptotic activity. This
      new cell-sampling technique facilitates the analysis of dynamic processes of
      hepatocyte culture inside a BAL.

PMID- 17518724
TI  - The potential use of enamel matrix derivative for in situ anterior cruciate
      ligament tissue engineering: a translational in vitro investigation.
AB  - Polyester scaffolds have been used as an alternative to autogenous tissues for
      the reconstruction of the anterior cruciate ligament (ACL). They are
      biocompatible and encourage tissue infiltration, leading to neoligament
      formation. However, rupture can occur, caused by abrasion of the scaffold against
      the bone tunnels through which it is implanted. Good early tissue induction is
      therefore considered essential to protect the scaffold from this abrasion. Enamel
      matrix derivative (EMD) is used clinically in the treatment of periodontal
      disease. It is a complex mix of proteins with growth factor-like activity, which
      enhances periodontal ligament fibroblast attachment, proliferation, and
      differentiation, leading to the regeneration of periodontal bone and ligament
      tissues. We hypothesized that EMD might, in a similar manner, enhance tissue
      induction around scaffolds used in ACL reconstruction. This preliminary
      investigation adopted a translational approach, modelling in vitro 3 possible
      clinical modes of EMD administration, to ascertain the suitability of each
      protocol for application in an animal model or clinically. Preliminary
      investigations in monolayer culture indicated that EMD had a significant dose
      dependent stimulatory effect (p < 0.05, n = 6) on the proliferation of bovine
      primary synovial cells. However, pre-treating culture plates with EMD
      significantly inhibited cell attachment (p < 0.01, n = 6). EMD's effects on
      synovial cells, seeded onto ligament scaffolds, were then investigated in several
      in vitro experiments modelling 3 possible modes for clinical EMD administration
      (pre-, intra-, and post-operative). In the pre-operative model, EMD was adsorbed
      onto scaffolds before the addition of cells. In the intra-operative model, EMD
      and cells were added simultaneously to scaffolds in the culture medium. In the
      post-operative model, cells were pre-seeded onto scaffolds before EMD was
      administered. EMD significantly inhibited cell adhesion in the pre-operative
      model (p < 0.05, n = 6) and had no significant benefit in the intra-operative
      model. In the post-operative model, the addition of EMD to previously cell-seeded
      scaffolds significantly increased their total deoxyribonucleic acid content (p <
      0.01, n = 5). EMD's stimulative effect on cell proliferation in vitro suggests
      that it may accelerate scaffold colonization by cells (and in turn tissue
      induction) in situ. However, its inhibitory effect on synovial cell attachment in
      vitro implies that it may only be suited to post-operative administration.

PMID- 17518725
TI  - Growth factors for clinical-scale expansion of human articular chondrocytes:
      relevance for automated bioreactor systems.
AB  - The expansion of chondrocytes in automated bioreactors for clinical use requires
      that a relevant number of cells be generated, starting from variable initial
      seeding densities in one passage and using autologous serum. We investigated
      whether the growth factor combination transforming growth factor beta
      1/fibroblast growth factor 2/platelet-derived growth factor BB (TFP), recently
      shown to enhance the proliferation capacity of human articular chondrocytes
      (HACs), allows the efficiency of chondrocyte use to be increased at different
      seeding densities and percentages of human serum (HS). HACs were seeded at 1,000,
      5,000, and 10,000 cells/cm2 in medium containing 10% fetal bovine serum or 10,000
      cells/cm2 with 1%, 5%, or 10%HS. The chondrogenic capacity of post-expanded HACs
      was then assessed in pellet cultures. Expansion with TFP allowed a sufficient
      number of HACs to be obtained in one passage even at the lowest seeding density
      and HS percentage and variability in cartilage-forming capacity of HACs expanded
      under the different conditions to be reduced. Instead, larger variations and
      insufficient yields were found in the absence of TFP. By allowing large numbers
      of cells to be obtained, starting from a wide range of initial seeding densities
      and HS percentages, the use of TFP may represent a viable solution for the
      efficient expansion of HACs and addresses constraints of automated clinical
      bioreactor systems.

PMID- 17518726
TI  - The use of ultrasonication to aid recellularization of acellular natural tissue
      scaffolds for use in anterior cruciate ligament reconstruction.
AB  - Tissue engineering offers a promising solution to the replacement of anterior
      cruciate ligament. A decellularized porcine patella tendon scaffold was produced
      by immersing whole tissues sequentially in hypotonic buffer, 0.1% (w/v) sodium
      dodecyl sulfate (SDS) in hypotonic buffer, and nuclease solution prior to
      sterilization with 0.1% (w/v) peracetic acid. Initial studies revealed that
      primary human tenocytes would attach to, but failed to penetrate into, the
      decellularized scaffold. A novel use of ultrasonication was therefore developed
      to allow extrinsic cells to migrate into the acellular scaffold. Various
      intensities of ultrasonication were tested in order to produce a microscopically
      more open porous matrix without damaging the overall architecture of the
      scaffold. Ultrasonication treatment with the intensity of 360 W and a pulse time
      of 1 s for a total of 1 min was found to be the optimal treatment. This process
      did not have a significant effect upon the biochemical constituents (collagen,
      glycosaminoglycans), nor did it denature the collagen. Moreover, the acellular
      sonicated scaffold retained the essential biomechanical characteristics of the
      native tissue. Primary human tenocytes penetrated into the center of whole
      acellular sonicated scaffolds over a 3-week period in static culture. The
      viability of the cells in the center of the scaffold (depth of circa 2.5 mm) was,
      however, compromised. To circumvent the problem of nutrient limitation, acellular
      sonicated scaffolds were split into fascicular scaffolds (500 mum thick). Cells
      seeded onto the fascicular scaffolds penetrated throughout the scaffold and
      remained viable after 3 weeks of culture. This study has shown that an acellular
      biocompatible tendon scaffold can be produced using 0.1% (w/v) SDS and that
      ultrasonication can provide a novel method to enhance the recellularization of
      decellularized natural tissues.

PMID- 17518727
TI  - Design strategies of tissue engineering scaffolds with controlled fiber
      orientation.
AB  - Tissue engineering is an emerging area of applied research with a goal of
      repairing or regenerating the functions of damaged tissue that fails to heal
      spontaneously by using cells and synthetic functional components called
      scaffolds. Scaffolds made of nanofibers (herein called "nano-fibrous scaffolds")
      play a key role in the success of tissue engineering by providing a structural
      support for the cells to accommodate and guiding their growth in the three
      dimensional space into a specific tissue. The orientation of these fibers is
      considered as one of the important features of a perfect tissue scaffold, because
      the fiber orientation greatly influences cell growth and related functions.
      Therefore, engineering scaffolds with a control over fiber orientation is
      essential and a prerequisite for controlling cell orientation and tissue growth.
      Recent advances in electrospinning have made it possible to create nano-featured
      scaffolds with controlled fiber orientation. Electrospinning is a
      straightforward, cost-effective, and versatile method, which is recently applied
      in engineering well-defined nano-fibrous scaffolds that hold promise in serving
      as a synthetic extra-cellular matrix (ECM). This article reviews the current
      trends in electrospinning nano-fibrous scaffolds with fiber orientation. A
      detailed mechanism involved in the spinning process is discussed, followed by
      experimental examples that show how the fiber orientation influences cellular
      growth behavior. This review is expected to be useful for readers to gain
      knowledge on the state-of-the-art of scaffold engineering by electrospinning.

PMID- 17518728
TI  - Recent advances in gene delivery for structural bone allografts.
AB  - In this paper, we review the progress toward developing strategies to engineer
      improved structural grafting of bone. Three strategies are typically used to
      augment massive bone defect repair. The first is to engraft mesenchymal stem
      cells (MSCs) onto a graft or a biosynthetic matrix to provide a viable
      osteoinductive scaffold material for segmental defect repair. The second strategy
      is to introduce critical factor(s), for example, bone morphogenetic proteins
      (BMPs), in the form of bone-derived or recombinant proteins onto the graft or
      matrix directly. The third strategy uses targeted delivery of therapeutic genes
      (using viral and nonviral vectors) that either transduce host cells in vivo or
      stably transduce cells in vitro for subsequent implantation in vivo. We developed
      a murine femoral model in which allografts can be revitalized via recombinant
      adeno-associated virus (rAAV) gene transfer. Specifically, allografts coated with
      rAAV expressing either the constitutively active BMP type I receptor Alk2
      (caAlk2), or the angiogenic factor vascular endothelial growth factor (VEGF)
      combined with the osteoclastogenic factor receptor activator of NF-kappa B ligand
      (RANKL) have remarkable osteogenic, angiogenic, and remodeling effects that have
      not been previously documented in healing allografts. Using histomorphometric and
      micro computed tomography (muCT) imaging we show that rAAV-mediated delivery of
      caAlk2 induces significant osteoinduction manifested by a mineralized callus on
      the surface of the allograft, which resembles the healing response of an
      autograft. We also demonstrate that the rAAV-mediated gene transfer of the
      combination of VEGF and RANKL can induce significant vascularization and
      remodeling of processed structural allografts. By contrast, rAAV-LacZ coated
      allograft controls appeared similar to necrotic allografts and lacked significant
      mineralized callus, neovascularization, and remodeling. Therefore, innovations in
      gene delivery offer promising therapeutic approaches for tissue engineering of
      structural bone substitutes that can potentially have clinical applications in
      challenging indications.

PMID- 17518729
TI  - Effect of transforming growth factor-beta and growth differentiation factor-5 on
      proliferation and matrix production by human bone marrow stromal cells cultured
      on braided poly lactic-co-glycolic acid scaffolds for ligament tissue
      engineering.
AB  - Tissue engineering of ligaments based on biomechanically suitable biomaterials
      combined with autologous cells may provide a solution for the drawbacks
      associated with conventional graft material. The aim of the present study was to
      investigate the contribution of recombinant human transforming growth factor beta
      1 (rhTGF-beta1) and growth differentiation factor (GDF)-5, known for their role
      in connective tissue regeneration, to proliferation and matrix production by
      human bone marrow stromal cells (BMSCs) cultured onto woven, bioabsorbable, 3
      dimensional (3D) poly(lactic-co-glycolic acid) scaffolds. Cells were cultured for
      12 days in the presence or absence of these growth factors at different
      concentrations. Human BMSCs attached to the suture material, proliferated, and
      synthesized extracellular matrix rich in collagen type I and collagen III. No
      differentiation was demonstrated toward cartilage or bone tissue. The addition of
      rhTGF-beta1 (1-10 ng/mL) and GDF-5 (10-100 ng/mL) increased cell content (p <
      0.05), but only TGF-beta1 also increased total collagen production (p < 0.05) and
      collagen production per cell, which is a parameter indicating differentiation. In
      conclusion, stimulation with rhTGF-beta1, and to a lesser extent with GDF-5, can
      modulate human BMSCs toward collagenous soft tissue when applied to a 3D hybrid
      construct. The use of growth factors could play an important role in the
      improvement of ligament tissue engineering.

PMID- 17518730
TI  - Preparation of a functionally flexible, three-dimensional, biomimetic poly(L
      lactic acid) scaffold with improved cell adhesion.
AB  - Poly(L-lactic acid) (PLLA) is widely used in tissue-engineering applications
      because of its degradation characteristics and mechanical properties, but it
      possesses an inert nature, affecting cell-matrix interactions. It is desirable to
      modify the surface of PLLA to create biomimetic scaffolds that will enhance
      tissue regeneration. We prepared a functionally flexible, biomimetic scaffold by
      derivatizing the surface of PLLA foams into primary amines, activated
      pyridylthiols, or sulfhydryl groups, allowing a wide variety of modifications.
      Poly(L-lysine) (polyK) was physically entrapped uniformly throughout the scaffold
      surface and in a controllable fashion by soaking the foams in an acetone-water
      mixture and later in a polyK solution in dimethylsulfoxide. Arginine-glycine
      aspartic acid-cysteine (RGDC) adhesion peptide was linked to the polyK via
      creating disulfide bonds introduced through the use of the linker N-succinimidyl
      3-(2-pyridylthiol)-propionate. Presence of RGDC on the surface of PLLA 2
      dimensional (2-D) disks and 3-D scaffolds increased cell surface area and the
      number of adherent mesenchymal stem cells. We have proposed a methodology for
      creating biomimetic scaffolds that is easy to execute, flexible, and
      nondestructive.

PMID- 17518731
TI  - Utility and control of proteoglycans in tissue engineering.
AB  - This review addresses various methods of integrating proteoglycans (PGs) into the
      design of engineered tissues and provides insight for designing tissue-engineered
      disease models that leverage current knowledge of PG biology. Even though PGs
      show immense possibilities in tissue-engineering applications, they have seldom
      been used to their full potential. The most common tissue-engineering application
      of PGs has been in scaffolds (matrigels and collagen-chondroitin sulfate
      matrices), in which PGs or their glycosaminoglycan (GAG) chains are incorporated
      into the scaffold to promote cell growth, tissue remodeling, and intracellular
      signaling. In addition, many studies have reported the total amount of PGs
      synthesized within engineered tissues but have not delineated which specific PGs
      or GAG classes are involved in engineered tissue development. In native tissues,
      various PGs are dynamically and differentially regulated to achieve specific
      biophysical and biological functions, such as compressibility and transparency.
      Therefore, the targeted modulation of specific PGs (via exogenous addition,
      endogenous stimulation with growth factors, or mechanical stimulation) may help
      engineered tissues to achieve native tissue properties. The PG composition of
      engineered tissues could also be modified to achieve disease models in vitro and
      thus provide a way to study the effect of external agents on PG-related disease
      mechanisms.

PMID- 17518732
TI  - Gene expression profiling of mouse articular and growth plate cartilage.
AB  - Articular cartilage is recalcitrant to repair and regeneration. Tissue
      engineering and regenerative medicine are potential strategies to treat the
      damage to articular cartilage. A thorough understanding of the gene expression
      profiles in articular cartilage and growth plate chondrocytes will be an
      important prerequisite for tissue engineering of cartilage. Regeneration is a
      recapitulation of embryonic development and morphogenesis. We used laser capture
      microdissection to capture the surface articular chondrocytes and the resting
      zone chondrocytes of growth plate from 14-day-old C57BL/6J mice. Total RNA was
      individually purified, pooled, and amplified by two rounds of in vitro
      transcription. Labeled cRNA probes were analyzed using the Affymetrix GeneChip
      Mouse Genome 430 2.0 Array. We identified 107 genes that were highly expressed by
      the surface articular chondrocytes and 130 genes that were highly expressed by
      the resting zone chondrocytes of growth plate (> or = fivefold). The expression
      of major matrix proteins aggrecan and collagen II were similar, while several
      morphogens and growth factors were differentially expressed by the surface
      articular chondrocytes and the resting zone chondrocytes of growth plate. The
      results of this investigation will be of use in the evaluation of tissue
      engineered cartilage.

PMID- 17518733
TI  - Ascorbic acid modulates proliferation and extracellular matrix accumulation of
      hyalocytes.
AB  - Ascorbic acid is known to influence proliferation and functional properties of
      several cell types and is therefore widely used in tissue engineering. In this
      study, the effect of ascorbic acid on the proliferation and functional properties
      of hyalocytes was evaluated. Hyalocytes were cultured with different amounts of
      ascorbic acid in classical two-dimensional (2-D) cultures and a three-dimensional
      (3-D) pellet culture system. Ascorbic acid enhanced hyalocyte proliferation dose
      dependently at concentrations between 0.1 and 3 microg/mL; proliferation was
      constant over a wide concentration range up to 150 microg/mL, concentrations of
      500 microg/mL showed toxic effects. In 2-D hyalocyte culture, the accumulation of
      glycosaminoglycans (GAG) and collagens increased in response to ascorbic acid
      supplementation of 10 or 200 microg/mL. Normalized to the cell number, GAG
      production was not influenced, whereas collagen production increased. These
      results could be verified in a pellet-like 3-D culture system. Ascorbic acid also
      influenced hyalocytes on the mRNA level; the expression of COL11A1 was clearly
      enhanced by ascorbic acid. To conclude, ascorbic acid modulates proliferation and
      collagen accumulation of hyalocytes; it also influences mRNA expression of the
      cells. Taken together with the fact that ascorbic acid is present in high
      concentrations in the vitreous body, this vitamin seems to be an important factor
      for in vitro hyalocyte culture.

PMID- 17518734
TI  - Cell adhesion on polyelectrolyte multilayer coated polydimethylsiloxane surfaces
      with varying topographies.
AB  - This article demonstrates that the micro-topography of the surface with respect
      to the pattern size and pitch influences cell adhesion and proliferation.
      Extensive research has shown the dependence of cell proliferation on substrate
      chemistry, but the influence of substrate topography on cell attachment has only
      recently been appreciated. To evaluate the effect of substrate physical
      properties (i.e., periodic microstructures) on cell attachment and morphology, we
      compared the response of several cell types (fibroblasts, HeLa, and primary
      hepatocytes) cultured on various polydimethylsiloxane (PDMS) patterns. PDMS has
      been used as an artificial construct to mimic biological structures. Although
      PDMS is widely used in biomedical applications, membrane technology, and
      microlithography, it is difficult to maintain cells on PDMS for long periods, and
      the polymer has proved to be a relatively inefficient substrate for cell
      adhesion. To improve adhesion, we built polyelectrolyte multilayers (PEMs) on
      PDMS surfaces to increase surface wettability, thereby improving attachment and
      spreading of the cells. Micrographs demonstrate the cellular response to physical
      parameters, such as pattern size and pitch, and suggest that surface topography,
      in part, regulates cell adhesion and proliferation. Therefore, varying the
      surface topography may provide a method to influence cell attachment and
      proliferation for tissue-engineering applications.

PMID- 17518735
TI  - Enhanced functions of vascular cells on nanostructured Ti for improved stent
      applications.
AB  - Vascular tissue possesses numerous nanostructured surface features, but most
      metallic vascular stents proposed to restore blood flow are smooth at the
      nanoscale. Thus, the objective of the present study was to determine in vitro
      vascular cell functions on nanostructured titanium (Ti) compared to conventional
      commercially pure (c.p.) Ti. Results of this study showed for the first time
      greater competitive adhesion of endothelial versus vascular smooth muscle cells
      on nanostructured Ti compared to conventional Ti after 4 hours. Moreover, when
      cultured separately, increased endothelial and vascular smooth muscle cell
      density was observed on nanostructured Ti compared to conventional c.p. Ti after
      1, 3, and 5 days; endothelial cells formed confluent monolayers before vascular
      smooth muscle cells on nanostructured Ti. Results also showed greater total
      amounts of collagen and elastin synthesis by vascular cells when cultured on
      nanostructured Ti. Since a major mode of failure of conventional vascular stents
      is the overgrowth of smooth muscle cells compared to endothelial cells, these
      results suggest that while the functions of both types of vascular cells were
      promoted on nanostructured c.p. Ti, endothelial cell functions (of particular
      importance, cell density or confluence) were enhanced over that of vascular
      smooth muscle cells. Thus, the present in vitro study showed that vascular stents
      composed of nanometer c.p. Ti particles may invoke advantageous cellular
      responses for improved stent applications.

PMID- 17518736
TI  - Stem cells from adipose tissue allow challenging new concepts for regenerative
      medicine.
AB  - The perspective of an innovative new concept integrating tissue-engineering
      techniques with an established surgical technique is described. The focus is
      primarily on a one-step surgical procedure using adipose tissue-derived
      mesenchymal stem cells, a calcium phosphate scaffold as a carrier, and a
      bioresorbable polymer cage to facilitate spinal interbody fusion. We address the
      harvesting and processing of clinically relevant quantities of adipose tissue
      derived mesenchymal stem cells, triggering of these stem cells toward lineage
      specific differentiation, seeding of the triggered stem cells on a bioresorbable
      scaffold, and implantation of the resulting tissue-engineered construct. The
      integrated steps can be accomplished within one surgical procedure in a surgical
      theater. Although the proposed concept has been developed for spinal fusion,
      potential application in other surgical disciplines is presumed realistic.

PMID- 17518737
TI  - 17-Beta estradiol enhances osteogenic and adipogenic differentiation of human
      adipose-derived stromal cells.
AB  - Adipose-derived stromal cells (ASCs) possess multiple differentiation potentials
      and may serve as a cell source, if effectively modulated, for regenerative
      medicine and tissue engineering. Due to estrogen's function in tissue and organ
      development through regulating cell proliferation and differentiation, we
      hypothesized that an estrogen supplement may effectively enhance the multiple
      differentiation potentials of human ASCs. 17-Beta estradiol (E2) was investigated
      for modulating in vitro osteogenic and adipogenic differentiation in human ASCs
      isolated from a healthy female donor. After ASCs' exposure to osteogenic and
      adipogenic differentiation medium supplemented with different concentrations of
      E2, osteogenic markers (alkaline phosphatase activity, extracellular matrix,
      calcium deposition, and osteocalcin expression) and adipogenic parameters (lipid
      accumulation and differentiated cell population) significantly improved.
      Estrogen's enhancement is dose dependent and linked to differing alpha and beta
      estrogen receptors. Our data preliminarily demonstrate that estrogen can modulate
      the differentiation, and potentially improve the efficiency of ASCs in stem cell
      based tissue engineering and regeneration. However, further study is needed to
      verify the regulatory functions of estrogen on ASC differentiations of donors
      with different ages and genders.

PMID- 17518738
TI  - Hypoxia inducible factor-1alpha deficiency affects chondrogenesis of adipose
      derived adult stromal cells.
AB  - Increased cartilage-related disease, poor regeneration of cartilage tissue, and
      limited treatment options have led to intense research in tissue engineering of
      cartilage. Adipose-derived adult stromal cells (ADAS) are a promising cell source
      for skeletal tissue engineering; understanding ADAS cellular signaling and
      chondrogenesis will advance cell-based therapies in cartilage repair.
      Chondrocytes are unique-they are continuously challenged by a hypoxic
      microenvironment. Hypoxia inducible factor-1-alpha (HIF-1alpha), a critical
      mediator of a cell's response to hypoxia, plays a significant role in chondrocyte
      survival, growth arrest, and differentiation. By using an established in vitro 3
      dimensional micromass system, we investigated the role of HIF-1alpha in
      chondrogenesis. Targeted deletion of HIF-1alpha in ADAS substantially inhibited
      the chondrogenic pathway specifically. In marked contrast, deletion of HIF-1alpha
      did not affect osteogenic differentiation but enhanced adipogenic
      differentiation. This study demonstrates the critical and specific interplay
      between HIF-1alpha and chondrogenesis in vitro.

PMID- 17518739
TI  - Early fetal healing as a model for adult organ regeneration.
AB  - Evidence is provided pointing out certain basic similarities, though not an
      identity, between the mechanisms of early fetal regeneration and induced organ
      regeneration in adults. These similarities favor a model of induced organ
      regeneration in which biologically active scaffolds block wound contraction and
      scar formation.

PMID- 17518740
TI  - Activation of the ERK1/2 cascade via pulsatile interstitial fluid flow promotes
      cardiac tissue assembly.
AB  - Deciphering the cellular signals leading to cardiac muscle assembly is a major
      challenge in ex vivo tissue regeneration. For the first time, we demonstrate that
      pulsatile interstitial fluid flow in three-dimensional neonatal cardiac cell
      constructs can activate ERK1/2 sixfold, as compared to static-cultivated
      constructs. Activation of ERK1/2 was attained under physiological shear stress
      conditions, without activating the p38 cell death signal above its basic level.
      Activation of the ERK1/2 signaling cascade induced synthesis of high levels of
      contractile and cell-cell contact proteins by the cardiomyocytes, while its
      inhibition diminished the inducing effects of pulsatile flow. The pulsed medium
      induced cardiac cell constructs showed improved cellularity and viability, while
      the regenerated cardiac tissue demonstrated some ultra-structural features of the
      adult myocardium. The cardiomyocytes were elongated and aligned into myofibers
      with defined Z-lines and multiple high-ordered sarcomeres. Numerous intercalated
      disks were positioned between adjacent cardiomyocytes, and deposits of collagen
      fibers surrounded the myofibrils. The regenerated cardiac tissue exhibited high
      density of connexin 43, a major protein involved in electrical cellular
      connections. Our research thus demonstrates that by judiciously applying fluid
      shear stress, cell signaling cascades can be augmented with subsequent profound
      effects on cardiac tissue regeneration.

PMID- 17518741
TI  - Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a
      fibrin spray accelerate healing in murine and human cutaneous wounds.
AB  - The nonhematopoietic component of bone marrow includes multipotent mesenchymal
      stem cells (MSC) capable of differentiating into fat, bone, muscle, cartilage,
      and endothelium. In this report, we describe the cell culture and
      characterization, delivery system, and successful use of topically applied
      autologous MSC to accelerate the healing of human and experimental murine wounds.
      A single bone marrow aspirate of 35-50 mL was obtained from patients with acute
      wounds (n = 5) from skin cancer surgery and from patients with chronic, long
      standing, nonhealing lower extremity wounds (n = 8). Cells were grown in vitro
      under conditions favoring the propagation of MSC, and flow cytometry and
      immunostaining showed a profile (CD29+, CD44+, CD105+, CD166+, CD34-, CD45-)
      highly consistent with published reports of human MSC. Functional induction
      studies confirmed that the MSC could differentiate into bone, cartilage, and
      adipose tissue. The cultured autologous MSC were applied up to four times to the
      wounds using a fibrin polymer spray system with a double-barreled syringe. Both
      fibrinogen (containing the MSC) and thrombin were diluted to optimally deliver a
      polymerized gel that immediately adhered to the wound, without run-off, and yet
      allowing the MSC to remain viable and migrate from the gel. Sequential adjacent
      sections from biopsy specimens of the wound bed after MSC application showed
      elongated spindle cells, similar to their in vitro counterparts, which
      immunostained for MSC markers. Generation of new elastic fibers was evident by
      both special stains and antibodies to human elastin. The application of cultured
      cells was safe, without treatment-related adverse events. A strong direct
      correlation was found between the number of cells applied (greater than 1 x 10(6)
      cells per cm2 of wound area) and the subsequent decrease in chronic wound size (p
      = 0.0058). Topical application of autologous MSC also stimulated closure of full
      thickness wounds in diabetic mice (db/db). Tracking of green fluorescent protein
      (GFP)+ MSC in mouse wounds showed GFP+ blood vessels, suggesting that the applied
      cells may persist as well as act to stimulate the wound repair process. These
      findings indicate that autologous bone marrow-derived MSC can be safely and
      effectively delivered to wounds using a fibrin spray system.

PMID- 17518742
TI  - Healing full-thickness cartilage defects using adipose-derived stem cells.
AB  - The purpose of this study was to evaluate the use of adipose-derived stem cells
      (ADSCs) as a source for full-thickness cartilage repair in an animal model.
      Autologous ADSCs were isolated and induced with growth medium and placed in a
      fibrin glue scaffold and into 3-mm x 4-mm full-thickness chondral defects in
      rabbits with negative controls. Specimens were evaluated for early healing using
      immunostaining, Western blotting, reverse transcriptase polymerase chain
      reaction, transfection with the Lac Z gene, and quantitative assessment. Twelve
      of 12 (100%) articular surface defects containing tissue-engineered stem cell
      constructs healed with hyaline-like cartilage, versus 1 of 12 (8%) in the control
      group (p < .001). There was complete healing to subchondral bone in 12 of 12
      experimental defects (100%), and 10 of 12 (83%) had seamless annealing to the
      native cartilage. Aggrecan, superficial zone protein, collagen type II messenger
      ribonucleic acid, and Lac-Z gene products were identified in 12 of 12
      experimental specimens, which exhibited a collagen type II:I protein ratio
      similar to that of normal rabbit cartilage. Quantitative histologic analysis
      revealed an average score of 18.2 of 21 in the experimental group, compared with
      10.0 in the controls (p = .001). Induced ADSCs supported in a fibrin glue matrix
      are a promising cell source for cartilage tissue engineering.

PMID- 17518743
TI  - Identification and characterization of a novel prespheroid 3-dimensional
      hepatocyte monolayer on galactosylated substratum.
AB  - Three-dimensional (3D) hepatocyte spheroids mimicking the structural and
      functional characteristics of hepatocytes in vivo were self-assembled onto a
      galactosylated polyethylene terephthalate (PET) substratum, and the dynamic
      process of spheroid formation was investigated using time-lapse confocal
      microscopy. Hepatocytes cultured on this galactosylated substratum formed small
      cell-aggregates within 12 h, which gradually merged into "island-like" clusters
      at approximately 1 day and spread to form prespheroid monolayer within 2 days;
      the prespheroid monolayer was stretched to fold into compact and larger 3D
      spheroids after 3 days. We compared the expressions of F-actin (cytoskeleton),
      phosphorylated focal adhesion kinase (p-FAK, cell-substratum interactions) and E
      cadherin (cell-cell interactions) during the dynamic process of 3D hepatocyte
      spheroid formation with the dynamic process of 2D hepatocyte monolayer formation
      on collagen substratum. Hepatocytes in the prespheroid monolayer stage exhibited
      the strongest cell-substratum interactions of all 4 stages during spheroid
      formation with cell-cell interactions and F-actin distribution comparable with
      those of the 3D hepatocyte spheroids. The prespheroid monolayer also exhibited
      better hepatocyte polarity (multidrug resistance protein 2) and tight junction
      (zonula occludens-1) formation, more-differentiated hepatocyte functions (albumin
      production and cytochrome P450 1 A activity), and higher sensitivity to
      hepatotoxicity than the conventional 2D hepatocyte monolayer. The transient
      prespheroid 3D monolayer could be stabilized on a hybrid glycine-arginine-glycine
      aspartic acid-serine (GRGDS)/galactose-PET substratum for up to 1 week and
      destabilized to form 3D spheroids in excess soluble GRGDS peptide.

PMID- 17518744
TI  - Nanofabrication and microfabrication of functional materials for tissue
      engineering.
AB  - The burgeoning field of regenerative medicine promises significant progress in
      the treatment of cardiac ischemia, liver disease, and spinal cord injury. Key to
      its success will be the ability to engineer tissue safely and reliably. Tissue
      functionality must be recapitulated in the laboratory and then integrated into
      surrounding tissue upon transfer to the patient. Scaffolding materials must be
      chosen such that the microenvironment surrounding the cells is a close analog of
      the native environment. In the early days of tissue engineering, these materials
      were largely borrowed from other fields, with much of the focus on
      biocompatibility and biodegradation. However, attention has shifted recently to
      cell-cell and cell-surface interactions, largely because of enabling technologies
      at the nanoscale and microscale. Studies on cellular behavior in response to
      various stimuli are now easily realized by using microfabrication techniques and
      devices (e.g., biomedical microelectromechanical systems). These experiments are
      reproducible and moderate in cost, and often can be accomplished at high
      throughput, providing the fundamental knowledge required to design biomaterials
      that closely mimic the biological system. It is our opinion that these novel
      materials and technologies will bring engineered tissues one step closer to
      practical application in the clinic. This review discusses their application to
      cardiac, liver, and nerve tissue engineering.

PMID- 17518745
TI  - Effects of the mechanical properties of collagen gel on the in vitro formation of
      microvessel networks by endothelial cells.
AB  - Vascularization by endothelial cells (ECs) is an essential element in tissue
      engineering of organoids. Morphogenesis of these cells is regulated not only by
      the biochemical properties of the extracellular matrix (ECM) but also by its
      mechanical properties. Here, we investigated the effect of substrate mechanical
      properties on the formation of capillary-like networks by ECs; in particular, we
      examined the three-dimensional (3D) configurations of the resulting networks.
      Bovine pulmonary microvascular ECs (BPMECs) were cultured on a series of collagen
      gels of different stiffness but the same collagen concentration. Imaging
      techniques revealed that cells cultured in rigid and flexible gels formed 3D
      networks via different processes; cells formed dense, thin networks in the
      flexible gel, whereas thicker and deeper networks were formed in the rigid gel.
      Cross-sections of the networks revealed that those formed within the rigid gel
      had large lumens composed of multiple cells, whereas those formed within the
      flexible gel had small, intracellular vacuoles. The expression of vinculin, a
      focal adhesion protein, appeared to change with the mechanical properties of
      collagen gel. Our results indicate that the mechanical properties of adhesion
      substrates play an important role in regulating 3D network formation.

PMID- 17518746
TI  - Poly-L-D-lactic acid scaffold in the repair of porcine knee cartilage lesions.
AB  - Articular cartilage injuries cause a major clinical problem because of the
      negligible repair capacity of cartilage. Autologous chondrocyte transplantation
      is a surgical method developed to repair cartilage lesions. In the operation,
      cartilage defect is covered with a periosteal patch and the suspension of
      cultured autologous chondrocytes is injected into the lesion site. The method can
      form good repair tissue, but new techniques are needed to make the operation
      easier and to increase the postoperative biomechanical properties of the repair
      tissue. In this study, we investigated poly-L,D-lactic acid (PLDLA) scaffolds
      alone or seeded with autologous chondrocytes in the repair of circular 6-mm
      cartilage lesions in immature porcine knee joints. Spontaneous repair was used as
      a reference. Histologic evaluation of the repair tissue showed that spontaneous
      repair exhibited higher scores than either PLDLA scaffold group (with or without
      seeded chondrocytes). The scaffold material was most often seen embedded in the
      subchondral bone underneath the defect area, probably because of the hardness of
      the PLDLA material. However, some of the cell-seeded and nonseeded scaffolds
      contained cartilaginous tissue, suggesting that invasion of mesenchymal cells
      inside nonseeded scaffolds had occurred. Hyaluronan deposited in the scaffold had
      possibly acted as a chemoattractant for the cell recruitment. In conclusion, the
      PLDLA scaffold material used in this study was obviously mechanically too hard to
      be used for cartilage repair in immature animals.

PMID- 17518747
TI  - Facilitated endogenous repair: making tissue engineering simple, practical, and
      economical.
AB  - Facilitated endogenous repair is a novel approach to tissue engineering that
      avoids the ex vivo culture of autologous cells and the need for manufactured
      scaffolds, while minimizing the number and invasiveness of associated clinical
      procedures. The strategy relies on harnessing the intrinsic regenerative
      potential of endogenous tissues using molecular stimuli, such as gene transfer,
      to initiate reparative processes in situ. In the simplest example, direct
      percutaneous injection of an osteogenic vector is used to stimulate bone healing.
      If necessary, additional progenitor cells and space-filling scaffolds can be
      provided by autologous bone marrow, muscle, fat, and perhaps other tissues. These
      can be harvested, processed, and reimplanted by simple, expedited, intraoperative
      procedures. Examples of repair of experimental osseous and osteochondral lesions
      in laboratory animals are described. If successful, these strategies will provide
      methods for tissue regeneration that are not only effective but also inexpensive,
      safe, and clinically expeditious. Although orthopaedic examples are given here,
      the technology should be more generally applicable.

PMID- 17518748
TI  - Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the
      art and novel application in organ printing.
AB  - Organ printing, a novel approach in tissue engineering, applies layered computer
      driven deposition of cells and gels to create complex 3-dimensional cell-laden
      structures. It shows great promise in regenerative medicine, because it may help
      to solve the problem of limited donor grafts for tissue and organ repair. The
      technique enables anatomical cell arrangement using incorporation of cells and
      growth factors at predefined locations in the printed hydrogel scaffolds. This
      way, 3-dimensional biological structures, such as blood vessels, are already
      constructed. Organ printing is developing fast, and there are exciting new
      possibilities in this area. Hydrogels are highly hydrated polymer networks used
      as scaffolding materials in organ printing. These hydrogel matrices are natural
      or synthetic polymers that provide a supportive environment for cells to attach
      to and proliferate and differentiate in. Successful cell embedding requires
      hydrogels that are complemented with biomimetic and extracellular matrix
      components, to provide biological cues to elicit specific cellular responses and
      direct new tissue formation. This review surveys the use of hydrogels in organ
      printing and provides an evaluation of the recent advances in the development of
      hydrogels that are promising for use in skeletal regenerative medicine. Special
      emphasis is put on survival, proliferation and differentiation of skeletal
      connective tissue cells inside various hydrogel matrices.

PMID- 17518749
TI  - Prolonged hypoxia concomitant with serum deprivation induces massive human
      mesenchymal stem cell death.
AB  - Mesenchymal stem cells (MSCs) have been proposed for the repair of damaged tissue
      including bone, cartilage, and heart tissue. Upon in vivo transplantation, the
      MSCs encounter an ischemic microenvironment characterized by reduced oxygen (O2)
      tension and nutrient deprivation that may jeopardize viability of the tissue
      construct. The aim of this study was to assess the effects of serum deprivation
      and hypoxia on the MSC survival rates in vitro. As expanded MSCs are transferred
      from plastic to a scaffold in most tissue engineering approaches, possibly
      inducing loss of survival signals from matrix attachments, the effects of a
      scaffold shift on the MSC survival rates were also assessed. Human MSCs were
      exposed for 48 hours to (i) a scaffold substrate shift, (ii) serum deprivation,
      and (iii) O2 deprivation. MSCs were also exposed to prolonged (up to 120 hours)
      hypoxia associated with serum deprivation. Cell death was assessed by Live/Dead
      staining and image analysis. The MSC death rates were not affected by the shift
      to scaffold or 48-hour hypoxia, but increased with fetal bovine serum (FBS)
      starvation, suggesting that between the two components of ischemia, nutrient
      deprivation is the stronger factor. Long-term hypoxia combined with serum
      deprivation resulted in the complete death of MSCs (99 +/- 1%), but this rate was
      reduced by half when MSCs were exposed to hypoxia in the presence of 10% FBS (51
      +/- 31%). These results show that MSCs are sensitive to the concurrent serum and
      O2 deprivation to which they are exposed when transplanted in vivo, and call for
      the development of new transplantation methods.

PMID- 17518750
TI  - The role of collagen cross-links in biomechanical behavior of human aortic heart
      valve leaflets--relevance for tissue engineering.
AB  - A major challenge in tissue engineering of functional heart valves is to
      determine and mimic the dominant tissue structures that regulate heart valve
      function and in vivo survival. In native heart valves, the anisotropic matrix
      architecture assures sustained and adequate functioning under high-pressure
      conditions. Collagen, being the main load-bearing matrix component, contributes
      significantly to the biomechanical strength of the tissue. This study
      investigates the relationship between collagen content, collagen cross-links, and
      biomechanical behavior in human aortic heart valve leaflets and in tissue
      engineered constructs. In the main loading direction (circumferential) of native
      valve leaflets, a significant positive linear correlation between modulus of
      elasticity and collagen cross-link concentration was found, whereas no
      correlation between modulus of elasticity and collagen content was found. Similar
      findings were observed in tissue-engineered constructs, where cross-link
      concentration was higher for dynamically strained constructs then for statically
      cultured controls. These findings suggest a dominant role for collagen cross
      links over collagen content with respect to biomechanical tissue behavior in
      human heart valve leaflets. They further suggest that dynamic tissue straining in
      tissue engineering protocols can enhance cross-link concentration and
      biomechanical function.

PMID- 17518751
TI  - Oxygen tension directs chondrogenic differentiation of myelo-monocytic
      progenitors during endochondral bone formation.
AB  - Synthesis of bone requires both essential progenitors to form the various
      structures and the correct microenvironment for their differentiation. To
      identify these factors, we have used a system that exploits bone morphogenetic
      protein's ability to induce endochondral bone formation rapidly. One of the
      earliest events observed was the influx and proliferation of fibroblastic cells
      that express both vascular smooth muscle cell markers, alpha smooth muscle actin
      (alpha SMA), smooth muscle myosin heavy chain, and the monocytic marker CD68. The
      expression of these factors was lost by days 4 to 5, coincident with the up
      regulation of Sox9 and the appearance of chondrocytes. Studies with a cyclization
      recombination (Cre)/lox system, in which a myeloid-specific promoter driving Cre
      recombinase can irreversibly unblock expression of beta-galactosidase only in
      cells of myeloid origin, showed specific activity in the newly formed
      chondrocytes. These results suggest that early chondrocyte progenitors are of
      myeloid origin. Simultaneous with this recruitment, we determined that a numbers
      of these cells were in a hypoxic state, indicative of a low-oxygen environment.
      The cells in the hypoxic regions were undergoing chondrogenesis, whereas cells in
      adjacent normoxic regions appeared to be assembling into new vessels, suggesting
      that the oxygen microenvironment is critical for establishment of the cartilage.

PMID- 17518752
TI  - Dose-dependent immunomodulatory effect of human stem cells from amniotic
      membrane: a comparison with human mesenchymal stem cells from adipose tissue.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) have been used for allogeneic
      application in tissue engineering but have certain drawbacks. Therefore, stem
      cells (SC)s derived from other adult tissue sources have been considered as an
      alternative. However, there is only limited knowledge on their immunomodulatory
      properties. The aim of our study was to compare the immunomodulatory potential of
      human amniotic mesenchymal and human amniotic epithelial cells with that of human
      adipose-derived SCs under identical experimental conditions. We have demonstrated
      a dose-dependent inhibition of peripheral blood mononuclear cell (PBMC) immune
      responses in mixed lymphocyte reactions (up to 66-93% inhibition) and
      phytohemagglutinin activation assays (up to 67-96% inhibition). The lowest SC-to
      PBMC ratio able to inhibit PBMC proliferation significantly was 1:8.
      Subcultivation (passage 2-6) did not alter immunoinhibitory properties, whereas
      cryopreservation significantly reduced the immunomodulatory potential. Using
      transwell systems, we have demonstrated an inhibition mechanism that is dependent
      on cell contact. Additionally, in coculture with allogeneic PBMCs, SCs were well
      tolerated and at most provoked mild alloreactions in singular cases. This study
      demonstrates, for the first time, contact- and dose-dependent immunosuppression
      of mesenchymal and epithelial amniotic SC populations, as well as of adipose
      tissue-derived SCs. All three cell types may be considered as possible
      alternatives to BMSCs for allogeneic application in tissue engineering.

PMID- 17518753
TI  - Characterization of arachnoidal cells cultured on three-dimensional nonwoven PET
      matrix.
AB  - PURPOSE: To culture physiologically functional primary arachnoidal cells on a
      suitable polymer substrate for an in-vitro model of the cerebrospinal fluid
      outflow pathway. METHODS: Primary cultures of arachnoidal cells were prepared
      within 24 hours post-mortem from brain tissue obtained from human cadavers at
      autopsy. Arachnoidal cells were characterized using immunocytochemistry and
      seeded onto needle punched non-woven poly(ethylene terephthalate)(PET) scaffolds.
      Metabolic rate, cell growth rate in log phase, morphologic assessment,
      immunocytochemistry, and protein analysis were used to characterize the cultures
      in both 2-D and 3-D-culture. Functional outflow assessment was performed using
      the Lucifer Yellow (LY) permeability assay and hydraulic conductivity (Lp)
      determination. RESULTS: Cells cultured on PET scaffold grew slightly slower than
      cells grown in 2-D-culture as measured by metabolic rate and growth rate,
      however, they often formed sheets that bridged between the adjacent scaffold
      filaments forming many junctional protein connections. LY permeability
      coefficients of 2-D cells were compared with cells from scaffolds, and were not
      significantly different (p > 0.05) for both culture conditions. Average Lp of
      cells from 2-D-culture and 3-D-scaffolds were compared and shown not to be
      significantly different. CONCLUSION: Based on the biochemical and functional
      analysis, it has been shown that cells cultured on 3D-PET scaffolds retained the
      same properties as cells from 2D-culture plates.

PMID- 17518754
TI  - Current state of the art in myocardial tissue engineering.
AB  - Myocardial tissue engineering aims to repair, replace, and regenerate damaged
      cardiac tissue using tissue constructs created ex vivo. This approach may one day
      provide a full treatment for several cardiac disorders, including congenital
      diseases or ventricular dysfunction after myocardial infarction. Although the ex
      vivo construction of a myocardium-like tissue is faced with many challenges, it
      is nevertheless a pressing objective for cardiac reparative medicine.
      Multidisciplinary efforts have already led to the development of promising viable
      muscle constructs. In this article, we review the various concepts of cardiac
      tissue engineering and their specific challenges. We also review the different
      types of existing biografts and their physiological relevance. Although many
      investigators have favored cardiomyocytes, we discuss the potential of other
      clinically relevant cells, as well as the various hypotheses proposed to explain
      the functional benefit of cell transplantation.

PMID- 17518755
TI  - Adhesion behavior of human bone marrow stromal cells on differentially wettable
      polymer surfaces.
AB  - An appropriate cellular response to implanted surfaces is essential for tissue
      regeneration and integration. In this study, we investigated how human bone
      marrow stromal cells (hBMSCs) respond to scaffold substrates. We prepared
      wettable polymer surfaces by exposing polymer sheets to radio frequency plasma
      discharge, which gradually oxidizes the polymer surface, increasing the roughness
      and greatly reducing the hydrophobicity. We found that hBMSCs adhered better to
      highly hydrophilic and rough surfaces than to hydrophobic and smooth surfaces. In
      addition, the cells flattened extensively on hydrophilic surfaces. Further, c-fos
      gene expression increased in parallel with the degree of hydrophilicity, whereas
      the expression of the c-myc gene was higher on hydrophobic than on hydrophilic
      surfaces. Finally, p53 gene expression was higher on more hydrophobic or
      hydrophilic surfaces than on moderately hydrophobic or hydrophilic surfaces.
      These results indicate that the biological signals induced by cell adhesion
      depend on the wettability of the surface to which the cells attach.

PMID- 17518756
TI  - Axial prevascularization of porous matrices using an arteriovenous loop promotes
      survival and differentiation of transplanted autologous osteoblasts.
AB  - Generation of axially vascularized bioartificial bone might be performed using
      matrix neovascularization in connection with osteoblast injection. We sought to
      evaluate whether prevascularization of porous hard matrices using an
      arteriovenous (AV) loop promotes survival of transplanted osteoblasts. A
      processed bovine cancellous bone matrix was inserted into the AV loop. Six weeks
      later, 5 x 10(6) carboxyfluorescein diacetate-stained osteoblasts were injected
      into the matrix (group A, n = 34). Osteoblast-seeded matrices without
      prevascularization were implanted subcutaneously as controls (group B, n = 32).
      Specimens were subjected to histologic, morphometric, and molecular-biological
      analysis after 1, 4, 8, and 16 weeks. Upon cell injection, matrices were
      completely vascularized. An intense foreign body reaction was observed in
      matrices from both groups. Group A was significantly superior to group B in terms
      of osteoblast survival at any time point. Expression of bone-specific genes was
      detected in the AV loop group but not in the subcutaneous control. Bone formation
      was only detectable in 1 long-term animal of group A. This study demonstrates for
      the first time that axial prevascularization increases the survival of implanted
      osteoblasts in porous matrices. Matrices with optimized biocompatibility might
      eventually facilitate generation of axially vascularized bone tissue after
      injection of osteogenic cells in the AV loop model.

PMID- 17518757
TI  - Gene response in endothelial cells cultured on engineered surfaces is regulated
      by shear stress.
AB  - In vitro endothelialization of small-diameter synthetic vascular prostheses
      confluently lined with cultured autologous endothelial cells (ECs) before
      implantation has been shown to increase their patency. Many authors have studied
      the effects of shear stress on EC gene response seeded on various substrates
      showing different gene expression profiles according to cell type, flow times, or
      shear type with different molecular biology techniques, but few studies have
      reported any EC gene response to shear stress when cells are seeded on vascular
      grafts. The purpose of this in vitro study was to investigate whether ECs were
      able to transduce shear stress at the level of the nucleus. Human saphenous vein
      ECs were seeded on glass slides coated with gelatin or fibrin glue or on 6-mm
      fibrin-glue-coated grafts. Then cells were exposed to 12 dyn/cm(2) for 4 h and
      ribonucleic acid (RNA) were extracted. The relative messenger RNA (mRNA)
      expression was studied using real-time quantitative polymerase chain reaction for
      the following mRNAs: von Willebrand Factor, tissue-plasminogen activator, CD31,
      vascular endothelial (VE)-cadherin, beta(1) integrin, and vascular endothelial
      growth factor receptor type 2. From parallel flow chambers, results have shown
      similar EC gene response on gelatin and fibrin glue under laminar shear stress
      with downregulation of prothrombotic genes, as well as upregulation of
      nonthrombotic genes and upregulation of adhesion molecules such as VE-cadherin,
      but some discrepancies are noted, with a downregulation of CD31 and kinase insert
      domain receptor (KDR) for the former, without significant variation for the
      latter. In comparison, results show upregulation of tissue type plasminogen
      activator gene and downregulation of KDR, VE-cadherin, and beta(1) integrin genes
      in ECs lining grafts. To conclude, the major finding of our study is to show that
      human saphenous vein ECs seeded on fibrin glue (in planar flow chambers or in
      tubular grafts) can be regulated using shear stress via gene expression changes
      in a nonthrombotic way.

PMID- 17518758
TI  - Sequence analysis of the Receptor Activity-Modifying Proteins family, new
      putative peptides and structural conformation inference.
AB  - The Receptor Activity-Modifying Proteins (RAMP) is a family constituted by a
      single N-terminal extracellular domain and a transmembrane region ending in a
      short cytoplasmic region. Due to their specific role in modulating the
      specificity of ligand binding in many class II G-Protein Coupled Receptors, these
      proteins are awaiting further characterization and elucidation of their
      structure. This was the aim of this study. We were able to find 13 new RAMP
      sequences including new protein sequences and predicted peptides from Expressed
      Sequence Tags and genomic DNA, all of them annotated in databases such as
      GeneBank, EMBL, Swissprot and ENSEMBL. The predicted peptides came from an array
      of different organisms including Teleostei and Elasmobranchii species, of which
      the latter was the most ancient RAMP sequence found. It was also possible to
      efficiently predict the 1D structure of the extracellular RAMP domain and its 3D
      conformation was inferred through a combination of bioinformatic approaches such
      as threading. The 1D structure of the extracellular RAMP domain was predicted as
      three alpha-helix domain. The most highly conserved residues in the RAMP family
      were found to be involved in critical functions. Bioinformatic data mining and
      multiple sequence alignment analysis were crucial for improving the
      characterization of RAMP proteins and prediction of their 1D and 3D
      configurations.

PMID- 17518759
TI  - T-iDT : tool for identification of drug target in bacteria and validation by
      Mycobacterium tuberculosis.
AB  - With the completion of the Human Genome Project in 2003, many new projects to
      sequence bacterial genomes were started and soon many complete bacterial genome
      sequences were available. The sequenced genomes of pathogenic bacteria provide
      useful information for understanding host-pathogen interactions. These data prove
      to be a new weapon in fighting against pathogenic bacteria by providing
      information about potential drug targets. But the limitation of computational
      tools for finding potential drug targets has hindered the process and further
      experimental analysis. There are many in silico approaches proposed for finding
      drug targets but only few have been automated. One such approach finds essential
      genes in bacterial genomes with no human homologue and predicts these as
      potential drug targets. The same approach is used in our tool. T-iDT, a tool for
      the identification of drug targets, finds essential genes by comparing a
      bacterial gene set against DEG (Database of Essential Genes) and excludes
      homologue genes by comparing against a human protein database. The tool predicts
      both the set of essential genes as well as potential target genes for the given
      genome. The tool was tested with Mycobacterium tuberculosis and results were
      validated. With default parameters, the tool predicted 236 essential genes and 52
      genes to encode potential drug targets. A pathway-based approach was used to
      validate these potential drug target genes. The pathway in which the products of
      these genes are involved was determined. Our analysis shows that almost all these
      pathways are very essential for the bacterial survival and hence these genes
      encode possible drug targets. Our tool provides a fast method for finding
      possible drug targets in bacterial genomes with varying stringency level. The
      tool will be helpful in finding possible drug targets in various pathogenic
      organisms and can be used for further analysis in novel therapeutic drug
      development. The tool can be downloaded from http://www.milser.co.in/research.htm
      and http://www.srmbioinformatics.edu.in/ forum.htm.

PMID- 17518760
TI  - Using Grid technology for computationally intensive applied bioinformatics
      analyses.
AB  - For several applications and algorithms used in applied bioinformatics, a bottle
      neck in terms of computational time may arise when scaled up to facilitate
      analyses of large datasets and databases. Re-codification, algorithm modification
      or sacrifices in sensitivity and accuracy may be necessary to accommodate for
      limited computational capacity of single work stations. Grid computing offers an
      alternative model for solving massive computational problems by parallel
      execution of existing algorithms and software implementations. We present the
      implementation of a Grid-aware model for solving computationally intensive
      bioinformatic analyses exemplified by a blastp sliding window algorithm for whole
      proteome sequence similarity analysis, and evaluate the performance in comparison
      with a local cluster and a single workstation. Our strategy involves temporary
      installations of the BLAST executable and databases on remote nodes at
      submission, accommodating for dynamic Grid environments as it avoids the need of
      predefined runtime environments (preinstalled software and databases at specific
      Grid-nodes). Importantly, the implementation is generic where the BLAST
      executable can be replaced by other software tools to facilitate analyses
      suitable for parallelisation. This model should be of general interest in applied
      bioinformatics. Scripts and procedures are freely available from the authors.

PMID- 17518761
TI  - Primer design for Whole Genome Amplification using genetic algorithms.
AB  - Whole Genome Amplification (WGA) is an important process to increase limiting
      amounts of genomic DNA prior to genomic analyses. Current amplification methods
      based on primer extension or strand displacement principles employ primers of
      partially or totally random sequence. In this paper, we present a method using
      Genetic Algorithms to optimize a single primer design to be used in a primer
      extension reaction to achieve unbiased WGA. Computational simulation and
      prediction of a suitable primer proposed two candidates NYP6-1 (ATCTCA) and NYP6
      2 (TGAGAT). NYP6-1 amplified to a maximum length of 2537 base pairs (bp), had
      genome coverage of approximately 45.62%, with an average of 493 and variance of
      163 amplicons per 1 megabasepairs (Mb). NYP6-2 amplified to a maximum length of
      2926 bp and covered 54.35% of the genome with an average of 579 and a variance of
      191 amplicons per Mb. In contrast, the original primer used in Degenerate
      Oligonucleotide-Primed PCR (DOP-PCR) had coverage of 20.93%, an average of 74 and
      variance of 188 amplicons per Mb when extended up to a length of 2000 bp.
      Successful WGA of miniscule amounts of genomic DNA requires the amplification
      method used to resolve issues on efficiency, accurate representation of the whole
      genome and ability to degraded DNA. The sequence NYP6-2 discovered using our
      method can be confidently used in a primer extension based protocol to perform
      quantitatively unbiased WGA.

PMID- 17518762
TI  - Improving the performance of an SVM-based method for predicting protein-protein
      interactions.
AB  - Predicting the interactions between all the possible pairs of proteins in a given
      organism (making a protein-protein interaction map) is a crucial subject in
      bioinformatics. Most of the previous methods based on supervised machine learning
      use datasets containing approximately the same number of interacting pairs of
      proteins (positives) and non-interacting pairs of proteins (negatives) for
      training a classifier and are estimated to yield a large number of false
      positives. Thinking that the negatives used in previous studies cannot adequately
      represent all the negatives that need to be taken into account, we have developed
      a method based on multiple Support Vector Machines (SVMs) that uses more
      negatives than positives for predicting interactions between pairs of yeast
      proteins and pairs of human proteins. We show that the performance of a single
      SVM improved as we increased the number of negatives used for training and that,
      if more than one CPU is available, an approach using multiple SVMs is useful not
      only for improving the performance of classifiers but also for reducing the time
      required for training them. Our approach can also be applied to assessing the
      reliability of high-throughput interactions.

PMID- 17518763
TI  - Identification of transcriptional regulators using binding site enrichment
      analysis.
AB  - To understand the transcriptional regulatory network in eukaryotic cells, it is
      essential to identify functional cis-regulatory sequences that interact with
      trans-acting factors. A number of algorithms have been developed to predict
      common cis-regulatory elements for co-regulated genes with similar expression
      patterns. However, previous methods usually deal with disjoint gene groups
      partitioned or clustered by arbitrary cutoffs, which might cause information
      losses. To preclude the defining step of gene set, we adopted enrichment analysis
      and termed the method binding site enrichment analysis (BSEA). BSEA was first
      applied for publicly available ChIP-on-chip data of c-MYC, MAX and E2F
      transcription factors, identifying significant enrichment for signatures of
      corresponding factors and potential co-activators. Using time-scaled expression
      profiling of 3T3-L1 adipogenesis, we observed enrichment for signatures of known
      adipogenic factors such as C/EBPalpha, C/EBPbeta and PPARgamma, temporally
      coincident with previous reports. BSEA was also applied to tissue-specific
      expression profiles of human and mouse, identifying well-known tissue-specific
      transcription factors such as HNF-4 in liver and MEF-2 in heart along with other
      putative tissue-specific regulators. With extended versatility coping with
      various kinds of microarray dataset, BSEA can identify key regulators for global
      microarray data in which transcriptional regulation plays a major role. As a
      generalized method, BSEA would help to elucidate the transcriptional regulatory
      networks, the primary challenges in functional genomics.

PMID- 17518764
TI  - A calcium dependent de-adhesion mechanism regulates the direction and rate of
      cell migration: a mathematical model.
AB  - Cell migration has long been studied by a variety of techniques and many proteins
      have been implicated in its regulation. Integrins, key proteins that link the
      cell to the extracellular matrix, are central to adhesion complexes whose
      turnover defines the rate of cell locomotion. The formation and disassembly of
      these adhesions is regulated by both intracellular and extracellular factors. In
      this study we have focused on the Ca2+-dependent protein network (module) that
      disassembles the adhesion complexes. We have developed a mathematical model that
      includes the Ca2+-dependent enzymes micro-calpain and phospholipase C (PLC) as
      well as IP3 receptors and stretch activated Ca2+ channels, all of which have been
      reported to regulate migration. The model also considers the spatial effects of
      Ca2+ propagation into lamella. Our model predicts differential activation of
      calpain at the leading and trailing edges of the cell. Since disassembly of
      integrin adhesive contacts is proportional to the degree of calpain activation,
      this leads to cell migration in a preferred direction. We show how the dynamics
      of Ca2+ spiking affects calpain activation and thus changes the disassembly rate
      of adhesions. The spiking is controlled by PLC activity and currents through
      stretch-activated Ca2+ channels. Our model thus combines the effects of various
      molecular factors and leads to a consistent explanation of the regulation of the
      rate and direction of cell migration.

PMID- 17518765
TI  - IMGT standardization for statistical analyses of T cell receptor junctions: the
      TRAV-TRAJ example.
AB  - The diversity of immunoglobulin (IG) and T cell receptor (TR) chains depends on
      several mechanisms: combinatorial diversity, which is a consequence of the number
      of V, D and J genes and the N-REGION diversity, which creates an extensive and
      clonal somatic diversity at the V-J and V-D-J junctions. For the IG, the
      diversity is further increased by somatic hypermutations. The number of different
      junctions per chain and per individual is estimated to be 10(12). We have chosen
      the human TRAV-TRAJ junctions as an example in order to characterize the required
      criteria for a standardized analysis of the IG and TR V-J and V-D-J junctions,
      based on the IMGT-ONTOLOGY concepts, and to serve as a first IMGT junction
      reference set (IMGT, http://imgt.cines.fr). We performed a thorough statistical
      analysis of 212 human rearranged TRAV-TRAJ sequences, which were aligned and
      analysed by the integrated IMGT/V-QUEST software, which includes
      IMGT/JunctionAnalysis, then manually expert-verified. Furthermore, we compared
      these 212 sequences with 37 other human TRAV-TRAJ junction sequences for which
      some particularities (potential sequence polymorphisms, sequencing errors, etc.)
      did not allow IMGT/JunctionAnalysis to provide the correct biological results,
      according to expert verification. Using statistical learning, we constructed an
      automatic warning system to predict if new, automatically analysed TRAV-TRAJ
      sequences should be manually re-checked. We estimated the robustness of this
      automatic warning system.

PMID- 17518766
TI  - Sequence-structure-function relation characterized in silico.
AB  - Methods for biological function recognition in silico appeared to be useful also
      for identifying characteristics of structure-to-function relations. The
      introduction of a three-dimensional Gauss function was assumed to represent the
      hydrophobic core in a protein molecule. The discrepancy between idealized "fuzzy
      oil-drop" and the observed one in real proteins appeared to be localized in the
      ligation site or in the area of biological function related part of protein
      molecule. The examples of proteins presented in this paper reveal that the
      structure-function relation can be evaluated and characterized also using the
      profile of the difference in value between idealized and real hydrophobicity
      distribution along the polypeptide chain. The specificity of particular
      polypeptide chain fragments in respect to their biological function and their
      specific participation in active site creation is discussed in this paper. The
      scale allowing comparison of different proteins in respect to their ligand
      binding sites characteristics is introduced.

PMID- 17518767
TI  - Detailed comparison of the protein-ligand docking efficiencies of GOLD, a
      commercial package and ArgusLab, a licensable freeware.
AB  - Molecular docking and virtual screening based on molecular docking have become an
      integral part of many modern structure-based drug discovery efforts. Hence, it
      becomes a useful endeavor to evaluate existing docking programs, which can assist
      in the choice of the most suitable docking algorithm for any particular study.
      The objective of the current study was to evaluate the ability of ArgusLab 4.0, a
      relatively new molecular modeling package in which molecular docking is
      implemented, to reproduce crystallographic binding orientations and to compare
      its accuracy with that of a well established commercial package, GOLD. The study
      also aimed to evaluate the effect of the nature of the binding site and ligand
      properties on docking accuracy. The three dimensional structures of a carefully
      chosen set of 75 pharmaceutically relevant protein-ligand complexes were used for
      the comparative study. The study revealed that the commercial package outperforms
      the freely available docking engine in almost all the parameters tested. However,
      the study also revealed that although lagging behind in accuracy, results from
      ArgusLab are biologically meaningful. This taken together with the fact that
      ArgusLab has an easy to use graphical user interface, means that it can be
      employed as an effective teaching tool to demonstrate molecular docking to
      beginners in this area.

PMID- 17518768
TI  - A database of simple sequence repeats from cereal and legume expressed sequence
      tags mined in silico: survey and evaluation.
AB  - Simple sequence repeats (SSRs) or microsatellites are an important class of
      molecular markers for genome analysis and plant breeding applications. In this
      paper, the SSR distributions within ESTs from the legumes soybean (Glycine max,
      representing 135.86 Mb), medicago (Medicago truncatula, 121.1 Mb) and lotus
      (Lotus japonicus, 45.4 Mb) have been studied relative to the distributions in
      cereals such as sorghum (Sorghum bicolor, 98.9 Mb), rice (Oryza sativa, 143.9 Mb)
      and maize (Zea mays, 183.7 Mb). The relative abundance, density, composition and
      putative annotations of di-, tri-, tetra- and penta-nucleotide repeats have been
      compared and SSR containing ESTs (SSR-ESTs) have been clustered to give a non
      redundant set of EST-SSRs, available in a database. Further, a subset of such
      candidate EST-SSRs from sorghum have been tested for their ability to detect
      polymorphism between Striga-susceptible, stay-green drought tolerant mapping
      population parent 'E 36-1' and its Striga-resistant, non-stay-green counterpart
      'N13'. Primer sets for 64% of the EST-SSRs tested produced a clear and specific
      PCR product band and 34% of these detected scorable polymorphism between the N13
      and E 36-1 parental lines. Over half of these markers have been genotyped on 94
      RILs from the (N13 x E 36-1)-based mapping population, with 42 markers mapping
      onto the ten sorghum linkage groups. This establishes the value of this database
      as a resource of molecular markers for practical applications in cereal and
      legume genetics and breeding. The primer pairs for non-redundant EST-SSRs have
      been designed and are freely available through the database
      (http://intranet.icrisat.org/gt1/ssr/ssrdatabase.html).

PMID- 17518769
TI  - MEGU: pathway mapping web-service based on KEGG and SVG.
AB  - Scientific visualization is a key technology to enhance our understanding of huge
      masses of omics data, especially for cell-wide, high-throughput measurements of
      the physiological networks. We have developed a web application that visualizes
      complex omics data of multiple layers simultaneously, including transcriptome,
      proteome, and metabolome, onto an integrated pathway diagram derived by
      connecting the individual KEGG pathway maps; the mapped images are generated in
      Scalable Vector Graphics for easy editing by hand or with computer programs or
      drawing software. The web application is available at
      http://megu.iab.keio.ac.jp/.

PMID- 17518770
TI  - Analysis of the signal transduction pathway of nickel-induced matrix
      metalloproteinase-2 expression in the human keratinocytes in vitro: preliminary
      findings.
AB  - BACKGROUND: Nickel can induce cellular and nuclear damages responsible for
      chronic diseases, like allergic contact dermatitis (ACD). We previously showed
      that matrix metalloproteinase-2 (MMP-2) gene expression was induced by nickel in
      nontumorigenic human keratinocytes cell line (HaCat). OBJECTIVE: To investigate
      the signal transduction pathways involved in gelatinolytic activity induced in
      HaCat under nickel stimulation. METHODS: We analyzed the involvement of protein
      kinase A (PKA), protein kinase C (PKC), tyrosine kinase (PTK), nuclear factor-kB
      (NF-kB) and activator protein-1 (AP-1) using specific inhibitors (H89, calphostin
      C, genistein, carpain and curcumin) by electrophoretic mobility shift assay,
      reverse transcription-polymerase chain reaction and gelatin zymography. RESULTS:
      Our results indicate that nickel-induced MMP-2 production was inhibited with PTK,
      PKC and AP-1 specific inhibitors. Moreover, both PKA and NF-kB were not involved
      in nickel pathway. CONCLUSIONS: Using HaCat, we showed that curcumin and
      genistein can revert nickel-induced MMP-2 upregulation. Whether the use of PTK
      and AP-1 inhibitors has therapeutic ramifications in the management of ACD
      remains to be investigated.

PMID- 17518771
TI  - Low prevalence of RAS-RAF-activating mutations in Spitz melanocytic nevi compared
      with other melanocytic lesions.
AB  - Melanocytic lesions, including Spitz nevi (SN), common benign nevi (CBN) and
      cutaneous metastatic melanoma (CMM), were analyzed for activating mutations in
      NRAS, HRAS and BRAF oncogenes, which induce cellular proliferation via the MAP
      kinase pathway. One of 22 (4.5%) SN tested showed an HRAS G61L mutation. Another
      lesion, a 'halo' SN, showed a BRAF V600E (T1796A) mutation. BRAF V600E mutations
      were found in two thirds (20/31) of CBN, while a further 19% (6/31) showed NRAS
      codon 61 mutations. One third of CMM (10/30) had various BRAF mutations of codon
      600, and a further 6% (2/31) showed NRAS codon 61 mutations. Seventeen SN tested
      for loss of heterozygosity (LOH) at 9p and 10q regions, known to be frequently
      deleted in melanoma, showed LOH at the 9p loci D9S942 and IFNA. A further lesion
      was found with low-level microsatellite instability at one locus, D10S214. The
      low rate of RAS-RAF mutations (2/22, 9.1%) observed in SN suggests that these
      lesions harbor as yet undetected activating mutations in other components of the
      RAS-RAF-MEK-ERK-MAPK pathway. Germline DNA from members of 111 multiple-case
      melanoma families, representing a range of known (CDKN2A) and unknown
      predisposing gene defects, was analyzed for germline BRAF mutations, but none was
      found.

PMID- 17518772
TI  - Cell adhesion protein expression in melanocytic matricoma.
AB  - Melanocytic matricoma is a rare neoplasm thought to recapitulate the hair
      follicle in anagen. The tumor forms a nodule in the dermis containing basaloid,
      intermediate and shadow cells admixed with pigmented melanocytes dispersed as
      single dendritic cells. Because cadherins and catenins are crucial in the
      development of hair tumors, we examined the expression of E(epithelial)-,
      P(placental)-, N(nerve)-cadherin and beta-catenin in a melanocytic matricoma. A
      66-year-old Caucasian woman with a history of breast cancer presented with a
      pigmented nodule on the shoulder. Pathology revealed a melanocytic matricoma with
      S-100 and HMB45-positive melanocytes. E- and P-cadherin were localized at the
      cell membrane of basaloid and differentiating keratinocytes, and in melanocytes,
      recapitulating the anagen hair. Both cadherins were absent in shadow cells. N
      cadherin was not expressed. Beta-catenin had a differential distribution, in the
      nucleus and cytoplasm of basaloid cells, but at the cell membrane in
      differentiating cells and negative in shadow cells, paralleling the expression of
      E- and P-cadherin. Our results support the previously hypothesized resemblance of
      the tumor to the hair bulb in anagen and suggest a transcriptional role of beta
      catenin in the development of this rare neoplasm.

PMID- 17518773
TI  - The expression of CD23 and CD40 in primary cutaneous B-cell lymphomas.
AB  - BACKGROUND: CD23 expression in normal B lymphocytes is limited to autoreactive B
      cells, naive B cells and mature B cells manifesting an activated phenotype. As a
      marker of hematologic dyscrasia/malignancy, expression of CD23 is associated with
      small lymphocytic lymphoma/chronic lymphocytic leukemia. An absence of CD23
      expression within small lymphocytes is typically seen in marginal zone lymphoma
      and mantle cell lymphoma. Positive CD23 expression amidst neoplastic cells in
      primary cutaneous B-cell lymphoma is not a reported phenomenon. METHODS: This
      paper reports nine patients with cutaneous B-cell lymphoma manifesting CD23
      expression. RESULTS: In seven of the nine cases CD23 expression was observed in
      the setting of recurrent disease, being present in both large and small
      lymphocytes. CD23 expression paralleled staining for CD40 in all but one case.
      CONCLUSIONS: A potential mechanism of CD23 upregulation may involve the anti
      apoptotic nuclear kappa beta CD40-CD40 ligand pathway. Neoplastic B cells
      manifesting CD23 expression could have a survival advantage, predisposing to
      recurrent disease and or oncogenic events permissive to disease progression.

PMID- 17518774
TI  - Immunohistochemical expression of beta-catenin, E-cadherin, cyclin D1 and c-myc
      in benign trichogenic tumors.
AB  - BACKGROUND: beta-catenin gene mutations have been reported in vast majority of
      pilomatrixomas (PMXs). beta-catenin, a component of the adhesion molecules of the
      cytoskeleton, is degraded at the cytoplasm. Excess cytoplasmic beta-catenin
      enters into the nucleus and activates the transcription of several genes encoding
      c-myc, cyclin D1 and others. Sublocation of beta-catenin has been demonstrated by
      immunohistochemistry. The aim of this study was to determine the role of beta
      catenin-related proteins in various benign trichogenic tumors. METHODS: We
      investigated the expression of beta-catenin, E-cadherin, c-myc and cyclin D1
      immunohistochemically, and the expression of these molecules were compared
      between two groups consisting of 12 PMXs and 12 other benign trichogenic tumors
      (OBTTs). RESULTS: In PMX group, nuclear and/or cytoplasmic expression of beta
      catenin was associated with a loss of membranous expression of E-cadherin (p =
      0.002). In OBTT group, a membranous expression of E-cadherin and beta-catenin was
      observed, and there was a stronger nuclear immunoreactivity of cyclin D1 compared
      with PMX group (p = 0.006). CONCLUSIONS: In PMX, nuclear and/or cytoplasmic beta
      catenin expression of tumoral cells is not related with beta-catenin-related gene
      expressions (c-myc or cyclin D1). The molecular behaviour of OBTTs is clearly
      different from that of PMXs in terms of to E-cadherin and beta-catenin
      expression.

PMID- 17518775
TI  - Use of p63 expression in distinguishing primary and metastatic cutaneous adnexal
      neoplasms from metastatic adenocarcinoma to skin.
AB  - p63, a recently identified homologue of the p53 gene, is mainly expressed by
      basal and myoepithelial cells in skin. Others and we have shown the value of p63
      in distinguishing primary adnexal tumors from visceral adenocarcinomas metastatic
      to skin. We now investigate the pattern of p63 expression in metastases from skin
      adnexal carcinomas and their cognate primaries and evaluate p63 expression in a
      larger case series of malignant cutaneous adnexal neoplasms. Immunohistochemical
      analysis for p63 was performed on 13 metastases of adnexal carcinomas and their
      corresponding primary tumors. Twenty visceral metastatic adenocarcinomas to the
      skin and 7 primary mucinous carcinomas with cutaneous or visceral origin were
      compared. The majority (90.9%) of primary adnexal tumors strongly expressed p63
      and their metastases labeled similar to their cognate primary tumors. With one
      exception, primary or metastatic mucinous carcinomas did not express p63.
      Metastases from two apocrine carcinomas lacked p63 expression. All other
      cutaneous metastases from internal adenocarcinomas were negative for p63.
      Analysis of p63 expression may assist in the differential diagnosis of primary
      adnexal carcinomas versus metastatic visceral adenocarcinomas to the skin.
      Metastases from adnexal carcinomas generally retain p63 expression similar to
      their associated primary tumors.

PMID- 17518776
TI  - Cytoid bodies in cutaneous direct immunofluorescence examination.
AB  - BACKGROUND: The clinical significance of scattered or grouped cytoid bodies seen
      on direct immunofluorescence (DIF) examination has not been systematically
      analyzed in a variety of disorders. METHODS: We prospectively studied skin biopsy
      specimens obtained from July 2002 to December 2005 for which DIF examination
      using immunoglobulin (Ig) A, IgG, IgM, C3 and fibrinogen had been performed.
      Slides with cytoid bodies were further reviewed to assess the number, intensity
      and location of the cytoid bodies and for other specific findings. These data
      were compared with both clinical records in the medical charts and pathologic
      findings from concurrent skin biopsies. RESULTS: Of 1080 DIF examinations
      performed during the study period, 117 (10.8%) had cytoid bodies. These specimens
      were from patients with 28 different cutaneous disorders, the most common of
      which were various forms of lupus erythematosus (29/117, 24.8%) and erythema
      multiforme (22/117, 18.8%). In 81 (69.2%) of these specimens, interface
      dermatitis was found histopathologically. CONCLUSION: Cytoid bodies are not
      infrequent on DIF examination and, in the absence of a clear diagnosis, might
      point toward several common disorders, particularly those involving interface
      dermatitis.

PMID- 17518777
TI  - US dermatopathology fellows career survey: 2004-2005.
AB  - BACKGROUND: Graduates of a dermatopathology fellowship may choose an academic
      career or a career in private practice. OBJECTIVE: To assess career plans of 2004
      2005 dermatopathology fellows and to correlate an academic career choice with
      factors identified in a national survey of US dermatopathology fellowship
      programs. METHODS: Surveys were mailed to 60 trainees at 45 dermatopathology
      fellowship programs across the United States. Pearson correlation analysis was
      used to interpret the data. RESULTS: Thirty-five surveys (58% response rate) were
      returned. Top five factors that correlated positively with an academic career
      choice were graduating from a non-US medical school, performing research during
      fellowship, importance of research in a career decision, completing a dermatology
      residency and publication requirement in fellowship. Top five factors that
      correlated positively with choosing a career in private practice were loan debt,
      importance of salary/earning potential, importance of job availability, being
      married and having an employed spouse. LIMITATIONS: Study limitations are a small
      sample size and potential response bias. CONCLUSION: Supporting research during
      fellowship, supporting applicants who completed a dermatology residency or
      graduated from a foreign medical school, providing loan forgiveness/repayment and
      increasing earning/salary potential in academic practice may encourage more young
      physicians to join the academic workforce.

PMID- 17518778
TI  - Acquired acrodermatitis enteropathica: case report of an atypical presentation.
AB  - Acrodermatitis enteropathica (ADE) is a rare genetic or acquired disorder of
      hypozincemia. It can be caused by impaired intestinal absorption of zinc or by
      poor consumption of the mineral. It is characterized by skin lesions on acral and
      periorificial areas and may be associated to alopecia, diarrhea and increased
      frequency of infections. We present an atypical presentation of ADE in a 33-year
      old women with a history of mental retardation and psoriasis that presented with
      lesions on the periorificial areas and extremities, and low plasma zinc levels.

PMID- 17518779
TI  - Plaque form of warty dyskeratoma - acantholytic dyskeratotic acanthoma.
AB  - We report the case of a 64-year-old man with a plaque-like lesion on the lower
      back. Clinically, squamous cell carcinoma was suspected, but the histological
      features resembled those of isolated Darier's disease or pemphigus vegetans. The
      lesion was removed with the final diagnosis of acantholytic dyskeratotic
      acanthoma. We discuss this case with special regard to the differential diagnosis
      of other isolated acantholytic acanthomas.

PMID- 17518780
TI  - Mucinous hidradenoma: a report of three cases.
AB  - Mucinous cutaneous adnexal tumors are an uncommon occurrence. We describe three
      cases of mucinous hidradenoma characterized by diffuse and prominent mucinous
      cell proliferation and discuss the relevant literature. The patients (two men and
      one woman) ranged in age from 32 to 72 years. The lesions were completely
      excised, and all patients were alive without evidence of disease (follow-up
      interval 3-4 years). Case 1 presented as a 1.3-cm eyelid nodule and histology
      showed a mucinous apocrine hidradenoma with a proliferation of mucinous cells and
      apocrine glands. Case 2, from the shoulder of a 40-year-old man, was a 2.5-cm
      well-circumscribed nodule composed of hyperplastic villoglandular proliferation
      of mucinous cells with focal squamous whorls and focal columnar glandular cells
      showing decapitation secretion. The tumor was also interpretated as a mucinous
      hidradenoma, most likely of follicular-apocrine origin. Case 3 was a 3.0-cm scalp
      nodule. The histology showed a mucinous clear-cell hidradenoma composed of
      numerous mucinous glands amidst small squamous cells with clear cytoplasm and a
      hyalinized fibrovascular stroma.

PMID- 17518781
TI  - Ductal eccrine carcinoma with squamous differentiation: apropos a case.
AB  - Sweat gland carcinomas are rare. Given this, they can pose a diagnostic challenge
      especially in shave biopsy specimens. We present a case of ductal eccrine
      carcinoma with extensive squamoid differentiation that was repeatedly
      misdiagnosed by multiple dermatopathologists as squamous cell carcinoma in the
      initial few biopsies. As the distinction between these two neoplasms is crucial
      to patient management, we highlight the histologic features of this uncommon
      entity to highlight the potential diagnostic pitfalls.

PMID- 17518782
TI  - Metastatic myxoid melanoma with partial regression of the primary lesion.
AB  - Myxoid melanoma is a rare variant of malignant melanoma. The diagnostic problems
      are obviously increased when it presents as amelanotic metastasis in a lymph
      node. An 82-year-old woman presented a subcutaneous mass in the right axilla. A
      thorough clinical investigation disclosed a pigmented black lesion on the right
      forearm. The right axillary lymph nodes and the pigmented lesion were resected.
      In the lymph nodes, proliferation of tumor cells with an abundant mucous
      substrate was noted. The cells proliferated in a variable pattern, and there were
      no melanin granules detected on hematoxylin-eosin-stained sections. However, we
      found melanin granules in the tumor cells observed under electron microscopy. In
      the pigmented lesion of the right forearm, there were small clusters of tumor
      cells with melanin granules, suggesting malignant melanoma. In the present case,
      myxoid metastasis occurred with the partial spontaneous disappearance of the
      primary nonmyxoid malignant melanoma.

PMID- 17518783
TI  - Generalized vasculitic exanthem following Loxosceles reclusa envenomation.
AB  - Brown recluse spider bites (BRSB) cause a myriad of reactions ranging from local
      necrosis to potentially lethal systemic involvement. Envenomation may induce a
      generalized exanthem known clinically but not described histologically. We report
      a 49-year-old female who developed a generalized exanthem 24 hours after BRSB.
      The histopathology demonstrated a necrotizing vasculitis similar to that seen at
      an envenomation site but without epidermal necrosis. Loxoscelism should be
      considered in patients residing in endemic areas who present with a vasculitic
      exanthem.

PMID- 17518784
TI  - Cutaneous epithelioid angiomatous nodule: report of a case and absence of
      microsatellite instability.

PMID- 17518786
TI  - The praxis of clinical knowledge: learning to care for paediatric patients with a
      congenital heart anomaly.
AB  - In Saudi Arabia, the major tertiary care unit for the treatment of cardiovascular
      disease is the King Faisal Heart Institute (KFHI). Its state of the art
      technology and patient profile facilitates nurses to become highly knowledgeable
      in the diversity of treatment modalities and nursing care of a range of
      paediatric pathology. Like many global nursing organizations, the KFHI is
      experiencing nursing shortages and nurses coming to work in this highly
      specialized area are lacking some of the basic understanding and skills
      development necessary to work efficiently and effectively in the area. This paper
      describes the work of the cardiovascular education team in developing a praxis
      based curriculum that equips nurses to not only function at a high level in the
      cardiovascular area but also facilitate success in their future careers when they
      leave Saudi Arabia.

PMID- 17518787
TI  - Psychometric testing of the Swedish version of the Philadelphia Geriatric Center
      Multilevel Assessment Instrument.
AB  - We examined whether the Swedish adaptation of the Philadelphia Geriatric Center
      Multilevel Assessment Instrument (PGCMAI) developed by Lawton meets criteria for
      reliability and validity in an elderly Swedish population with locomotor
      disability. Data were collected, using the mid-length version of the instrument,
      from 199 elderly people with locomotor disability in two Swedish counties.
      Reliability was determined by Cronbach's alpha and construct validity was tested
      by means of exploratory factor analysis. Comparison was made with the
      Standardized Practical Equipment (SPE) test. Factor analysis identified eight
      factors, which were comparable to the original eight domains. There was a logical
      correlation between the PGCMAI and the SPE test. Further psychometric testing is
      recommended on other groups of elderly people.

PMID- 17518788
TI  - Reflective practice in nursing care: embedded assumptions in qualitative studies.
AB  - Qualitative nursing researchers have long recognized that reflective practice
      (RP) seems to be a valuable tool in nursing care. The aim of the present meta
      study was to analyse current qualitative research on RP in nursing care, in order
      to create and synthesize the knowledge and the understanding of registered
      nurses' RP. Using a meta-study synthesis approach, embedded assumptions were
      identified in qualitative studies that have influenced the way researchers have
      interpreted and made sense of RP in nursing care. Despite empirical focus in
      research on RP in nursing care, it was found that assumptions about RP were
      predominantly based on theory. The reflective movement within the practice of
      nursing care has mainly a constructivist epistemology, based on learning from
      experience. The individual nurse's RP capability is essential in providing and
      improving ethical and holistic nursing care.

PMID- 17518789
TI  - Elderly destitution in Ile-Ife community of Osun State, Nigeria.
AB  - Many studies have been conducted on the elderly, but none has ever paid
      particular attention to the increasing rate of destitution in the rural
      communities, where the elderly serve as agents for sustenance and transmission of
      culture. This study is descriptive in nature and has adopted qualitative
      perspective in order to identify and examine the factors that have contributed to
      the state of elderly in destitution in Ile-Ife, Nigeria. It has also examined the
      feelings and reactions of the subjects of the study and has documented how their
      lifestyles affect their health status. Sixteen elderly people in destitution were
      traced and interviewed in Ile-Ife community. At each location, where an elderly
      in destitution was located, at least an elderly chief and a resident were located
      for interview. Data collected were analysed using Textbase Beta package for
      qualitative analysis. The study found that communal feud, violence and conflicts
      were factors that created unhappiness for the elderly, and the lack of adequate
      support from the immediate households consequently led to their homelessness. The
      study documented that the elderly in destitution lack good hygiene and nutrition,
      and equally suffer self-neglect and mental confusion. The study concludes that
      peaceful coexistence, communal security, and familial care and support are
      important factors that promote happiness and successful ageing. It also maintains
      that focused health education is highly essential for the households and
      caregivers of the elderly in rural community.

PMID- 17518790
TI  - Getting on with life: accepting the permanency of an implantable cardioverter
      defibrillator.
AB  - Increasing numbers of people with cardiovascular disease are requiring the
      insertion of Implantable Cardioverter Defibrillators (ICDs). Although these
      devices are an effective life-saving treatment, psychological distress sometimes
      accompanies their insertion. A qualitative approach was used to explore the
      experiences, concerns and needs of recipients of the device in Western Australia.
      Twenty-two tape-recorded interviews were carried out and transcribed verbatim.
      This paper focuses on the physical and psychological adjustments following the
      insertion of the device. A central theme of 'getting on with it' used to cope
      with the permanency of the device was identified. This was an approach to life in
      which the presence of the device was accepted and then put aside while life was
      continued and optimized. This study provides directions for the identification of
      persons who might be experiencing difficulties adjusting, or who are taking
      extended amounts of time to accept the permanency of the device.

PMID- 17518791
TI  - The role of significant others in the care of women with breast cancer.
AB  - This study seeks to gain knowledge of how significant others experience the
      nursing care of women with breast cancer and what their own caring needs might
      be. The overall research design is a clinical application research within the
      hermeneutic tradition. Thirty-seven significant others have contributed their own
      narratives about the care on the basis of open, structured questions. The
      narratives have been submitted to an analysis of contents. The result shows that
      significant others have no given place in nursing care. Their place in nursing
      care is to look on, be present or be ignored. No matter what their place is, the
      significant others feel a need for caring conversations and information in an
      ethical manner. The faith and trust of significant others, the sharing, sense of
      communion and the information about woman's illness strengthen the significant
      others' own vitality. Their inmost desire concerns the sensitiveness of
      caregivers with regard to the woman's as well as the significant others' personal
      needs. If space is allowed and this desire meets with response, significant
      others can constitute a source of strength in the care of the woman suffering
      from breast cancer.

PMID- 17518792
TI  - Clinical usefulness and feasibility of using Reality Orientation with patients
      who have dementia in acute care settings.
AB  - Reality Orientation (RO) was developed as a strategy to assist people with
      dementia to improve their orientation and everyday function. Although its
      efficacy has been extensively studied in long-term care facilities, its
      effectiveness has rarely been examined in acute care settings. The aim of this
      review was to examine the studies cited in systematic reviews of RO to determine
      the potential clinical usefulness and the feasibility of using RO in acute care
      settings. Based on this information, the authors make recommendations for future
      research in this area. The feasibility of implementing RO in acute care poses
      challenges because of the short time a patient is in hospital and their ability
      to participate given their acute medical condition. Although the efficacy and
      feasibility of using RO in acute care settings have not been sufficiently
      examined, its potential to improve care should not be ignored. A comprehensive
      and rigorous study is necessary to investigate the usefulness of RO in the acute
      care setting and to help establish clinical guidelines for dementia care in the
      context of acute care nursing.

PMID- 17518793
TI  - Families' needs when a child is long-term ill: a literature review with reference
      to nursing research.
AB  - This article reports a literature review which draws together findings targeting
      families' needs when a child is long-term ill. The databases PubMed and CINHAL
      were searched from 1999 to 2003 during February 2004. The search terms were child
      health care, family caregivers, and needs and combinations of these. The search
      was limited to articles published in English and the Scandinavian languages. The
      analysis entailed a series of comparisons across articles focusing on major areas
      of inquiry and patterns of results. Various levels of needs are described, based
      on individual, family and social needs.

PMID- 17518794
TI  - Who makes the diagnosis? The role of clinical skills and diagnostic test results.
AB  - RATIONALE, AIMS AND OBJECTIVES: Advances in medicine have led to a multitude of
      diagnostic tests. The contribution of the clinical skills of the general
      internist in the context of all these advances is unknown. Our objective was to
      assess the relative contributions of clinical skills and diagnostic test results
      in arriving at a final diagnosis. METHODS: Records were retrospectively reviewed
      from 248 consecutive patients admitted to a general internal medicine hospital
      service during a 3-month period in 2000. All diagnostic evaluations that yielded
      the final diagnosis were recorded along with the date and time they were
      performed. Diagnostic credit was given to the evaluation that yielded the
      diagnosis at the earliest point in time. RESULTS: All cases had a firm diagnosis
      by 3 months after hospitalization. Of the 248 patients, 246 received a final
      diagnosis during hospitalization. The diagnoses were made by use of the clinical
      judgement of the general internist in 50.4% of the cases, a radiologic study in
      31.7%, a blood test or culture result in 9.4%, biopsy findings in 3.3% and
      various other diagnostic studies (endoscopy, echocardiography, electromyography
      and electroencephalography) in 5.2%. Clinicians provided the correct diagnosis
      significantly more often than radiologic studies (P = 0.0015), which was the next
      most useful type of diagnostic evaluation. CONCLUSION: Although technology has
      become increasingly available in clinical practice, clinical expertise and skills
      are still important factors with respect to making correct, timely diagnoses in
      hospitalized patients.

PMID- 17518795
TI  - An evaluation of two Rapid Access Chest Pain Clinics in central Lancashire, UK.
AB  - AIM: The aim of the project was to assess critically, using Maxwell's six
      dimensions, the quality of the services provided by the two Rapid Access Chest
      Pain Clinics (RACPCs) in Central Lancashire. METHODS: Data on the actual use of
      the clinic was obtained from the two RACPCs. A record linkage exercise between
      the database of patients from the RACPC and HES/mortality data was performed.
      Expected use of the clinic was established from the performance of other RACPCs
      and from published angina incidence figures. Patient and general practitioner
      views were obtained by conducting questionnaire surveys. KEY RECOMMENDATIONS: (1)
      Clinic is providing a valuable service and should be continued. (2) A
      standardized database should be created which includes ethnicity and final
      diagnosis. (3) Alternative methods for rapid diagnosis and management of chest
      pain need to be provided for patients who are not suitable for the exercise
      electrocardiogram. (4) Referral criteria should be redrafted in order to remove
      the exclusion criteria for patients with chest pain of longer duration than 3
      months. (5) Further resources need to be targeted at cardiology outpatients and
      revascularizations, as waiting times for patients with a positive test are felt
      to be too long.

PMID- 17518796
TI  - The clinical and cultural factors in classifying low back pain patients within
      Greece: a qualitative exploration of Greek health professionals.
AB  - RATIONALE, AIMS AND OBJECTIVES: Identifying homogenous subgroups of low back pain
      (LBP) patients is considered a priority in musculoskeletal rehabilitation and is
      believed to enhance clinical outcomes. In order to achieve this, the specific
      features of each subgroup need to be identified. The aim of this study was to
      develop a list of clinical and cultural features that are included in the
      assessment of LBP patients in Greece, among health professionals. This 'list'
      will be, utilized in a clinical study for developing LBP subgroups. METHODS:
      Three focus groups were conducted, each one comprising health professionals with
      homogenous characteristics and all coordinated by a single moderator. There were:
      11 physiotherapists (PTs) with clinical experience in LBP patients, seven PTs
      specialized in LBP management, and five doctors with a particular spinal
      interest. The focus of discussions was to develop a list of clinical and cultural
      features that were important in the examination of LBP. Content analysis was
      performed by two researchers. RESULTS: Clinicians and postgraduates developed
      five categories within the History (Present Symptoms, History of Symptoms,
      Function, Psychosocial, Medical History) and six categories within the Physical
      Examination (Observation, Neurological Examination, Active and Passive Movements,
      Muscle Features and Palpation). The doctors identified four categories in History
      (Symptomatology, Function, Psychosocial, Medical History) and an additional in
      Physical Examination (Special Tests). All groups identified three cultural
      categories; Attitudes of Health Professionals, Patients' Attitudes and Health
      System influences. CONCLUSION: An extensive Greek 'list' of clinical and cultural
      features was developed from the groups' analysis. Although similarities existed
      in most categories, there were several differences across the three focus groups
      which will be discussed.

PMID- 17518797
TI  - Using an interactive voice response system to improve patient safety following
      hospital discharge.
AB  - BACKGROUND: Patients often experience complications when transitioning from
      hospital to home. These complications are frequently related to poor monitoring.
      An interactive voice response system (IVRS) could improve post-discharge
      monitoring. OBJECTIVE: To determine the feasibility and utility of an IVRS to
      monitor patients following hospital discharge. DESIGN: Prospective cohort study
      at an academic health sciences centre. PATIENTS: Consecutive internal medicine
      patients who had a touch-tone telephone, spoke English, had no cognitive
      impairments and were discharged home. MEASUREMENTS: Feasibility was defined as
      the proportion of patients reached by the IVRS and the proportion completing an
      IVRS-based survey. Utility was defined as the percentage of patients whose
      outcomes could have been changed by the IVRS. METHODS: We programmed the IVRS to
      call patients and administer a simple survey 48 hours after discharge. The
      survey's objective was to identify all patients with new health problems. Such
      patients were telephoned by a nurse to clarify and address the problem. RESULTS:
      We enrolled 77 patients who were predominantly male (68%), elderly (median age 65
      years) and chronically ill (median number of co-morbidities = 3). The IVRS
      reached 45 of the 77 patients (58.4%). Forty patients (51.9%) answered all
      questions on the survey. Twenty patients (26%, 95% CI 17%-37%) indicated new or
      worsening symptoms, problems with their medications, or requested to talk to the
      clinic nurse. For 10 patients (13%, 95% CI 7%-22%), the IVRS could have made a
      difference in their outcome. CONCLUSION: Using an IVRS, we were able to identify
      several important new health concerns arising following hospital discharge.
      Subtle changes could increase the feasibility and utility of IVRS technology in
      improving post-discharge outcomes.

PMID- 17518798
TI  - The assessment of criterion audit cycles by external peer review - when is an
      audit not an audit?
AB  - INTRODUCTION: Clinical audit has failed to fully deliver the rewards initially
      envisaged. Contributory factors include: an ill-defined approach to audit; the
      assumption that health care professionals can intuitively apply audit methods;
      and the lack of a system to 'quality assure' the process. A method of criterion
      audit was defined and developed in conjunction with an instrument to facilitate
      trained General Practitioner (GP) assessors in the review of colleagues' audit
      projects. Given the potential for improving audit practice, this study aimed to
      define the methodological factors that contributed to 'unsatisfactory' audits as
      judged by peer assessors. METHODS: West of Scotland GPs voluntarily submitted a
      criterion audit in a standard format for review by two trained colleagues using
      an assessment instrument. Audits judged unsatisfactory and associated educational
      feedback were subjected to content analysis. RESULTS: Between 1999 and 2004, 336
      audits were submitted, of which 132 (39%) were judged to be unsatisfactory. Of
      these, 118 audits (89%) had a methodological issue identified in the initial
      project design (e.g. defining criteria) that effectively invalidated the audit.
      119 projects (90%) were also judged to have at least one deficiency in the data
      analysis or change management stages of the audit (e.g. implementing inadequate
      change). CONCLUSION: A range of audit method issues was found. The proportion of
      unsatisfactory audits may point to a larger problem beyond this sample, which may
      have implications for health care quality. If audit practise is to be consistent
      and rigorous, consideration should be given to assessing the standard of this
      activity.

PMID- 17518799
TI  - General practitioners' perceptions and attitudes to infertility management in
      primary care: focus group study.
AB  - BACKGROUND: Infertility management in primary care is variable. National
      Institute of Clinical Excellence have recommended hysterosalpingography (HSG) as
      a first-line investigation for tubal assessment. Aim To explore general
      practitioners' (GPs) perceptions of, and attitudes to, the initial management of
      the infertile couple and their views on open access to HSG. METHOD:  DESIGN:
      Qualitative study using three focus groups. SETTING: Seven general practices in
      Newcastle upon Tyne and Northumberland. SUBJECTS: We purposively selected the
      three focus groups to provide a range of GPs' views. In total 13 practitioners
      participated: 11 GPs, one GP registrar and one nurse practitioner. RESULTS: The
      key themes to emerge were: (1) perceived professional responsibilities, (2)
      uncertainty and lack of knowledge, (3) consistency of approach to the initial
      management of infertility, and (4) access to infertility services. Some GPs felt
      that they should do all they possibly could, while others felt it was the
      responsibility of the infertility specialist. Uncertainty and lack of knowledge
      was linked to the relative infrequency of primary care infertility consultations
      and the difficulty 'keeping up to date' with rapidly advancing reproductive
      technologies in tertiary care. Some GPs subscribed to the notion of one suitably
      trained clinician delivering the service on behalf of a group of GPs. Some were
      unsure where HSG fitted into the overall management plan, but they were
      comfortable with following recommended guidelines. CONCLUSIONS: GPs recognize an
      advocacy role and many take on a significant degree of clinical responsibility
      welcoming the introduction of a new technology in primary care. Nevertheless, GPs
      feel that they lack proficiency and have little opportunity to rehearse the
      necessary skills. These findings contribute to an understanding of the management
      of infertility, an infrequently presenting problem in primary care.

PMID- 17518800
TI  - Which factors are associated with a successful outcome in a weight management
      programme for obese children?
AB  - AIMS AND OBJECTIVE: To identify factors important in determining whether an obese
      child achieves significant reductions in Body Mass Index Standard Deviation Score
      (BMI SDS) within a UK, hospital-based paediatric obesity service aimed at
      lifestyle modification. DESIGN: Observational Study. SUBJECTS: 137 obese children
      (63 boys) who have attended our childhood obesity service within the last three
      and a half years at The Royal Hospital for Children, Bristol, UK. MEASUREMENTS:
      BMI SDS with a target reduction of - 0.5 or greater. RESULTS: 70% of children
      achieved reductions in BMI SDS with 18% achieving the target reduction. In those
      attending the clinic for a year or more the levels improved to 83% and 28%
      respectively. Age was found to be the most important predictor with younger
      children achieving larger reductions in BMI SDS. More boys than girls were likely
      to achieve target reductions in BMI SDS and those without a parental history of
      obesity were more likely to achieve greater reductions in BMI SDS. Socio-economic
      status did not appear to impact upon the child's level of success. CONCLUSIONS:
      In families of obese children, motivated to seek help by attending a hospital
      based weight control clinic, improvements in BMI are possible by a simple
      approach of education and continued support. Improvement is greatest in younger
      children with maximal benefit being seen in boys without a parental history of
      obesity. We believe this emphasizes the importance of identifying significant
      obesity in primary school aged children, who seem most likely to benefit from
      simple lifestyle modification, while many older children may require additional
      intervention programmes to improve BMI.

PMID- 17518801
TI  - Effects of a behaviour independent financial incentive on prescribing behaviour
      of general practitioners.
AB  - RATIONALE AND OBJECTIVES: It is difficult to keep control over prescribing
      behaviour in general practice. The purpose of this study was to assess the
      initial effects of a behaviour independent financial incentive on the volume of
      drug prescribing of general practitioners (GPs). DESIGN: 2-Year Controlled Before
      After study with an intervention region and a concurrent control region. SETTING
      AND PARTICIPANTS: GPs in two regions in the Netherlands (n = 119 and n = 118).
      INTERVENTION: A financial incentive for prescribing according to local guidelines
      on specific drugs or drug categories. The financial incentive consisted of a non
      recurrent, behaviour-independent allowance. MAIN OUTCOME MEASURE: Change in the
      number of prescriptions for 10 targeted drugs or drug groups. RESULTS:
      Significant changes were seen only in three types of antibiotics and in
      recommended gastric medicines. In almost all cases, effects were temporary.
      CONCLUSION: Behaviour independent financial incentives can be a help in changing
      prescription behaviour of GPs, but effects are small-scale and temporary.

PMID- 17518802
TI  - Bridging the gap between clinical practice and diagnostic clinical epidemiology:
      pilot experiences with a didactic model based on a logarithmic scale.
AB  - Rationale From general practitioners to academic staff, clinicians continue to
      have difficulties in applying clinical epidemiology in their everyday work. They
      do not fully understand the logical rules behind the numbers and they do not
      recognize these rules in their work. We present a new model where the pre-test
      and the post-test probabilities are converted to log10 of odds, and the
      likelihood ratio (LR) to its own log10. Methods Following Bayes' theorem, adding
      the log10LR to the log10 pre-test odds gives the log10 post-test odds, which can
      easily be represented on a logarithmic scale. In addition, by rounding the
      log10LR to half the unit, we create classes of discriminative power of tests,
      close to intuitive estimation. This model generates also a user-friendly diagram,
      adding considerably to the understanding of Bayes' theorem. We evaluated the
      effect of the rounding, the current use of the classical model and the
      acceptability of the new model. Results Rounding 10 disease characteristics to
      half the unit gives an absolute error of less than half a unit. After six
      explanations of Bayes' theorem, only 6/16 medical students were capable of
      answering simple questions about predictive value. When asked about weight of
      disease characteristics, no one of the 50 clinicians mentioned sensitivity,
      specificity, predictive value or LR. With the new model, more than 80% of
      trainees found medical decision making easier to understand and recognized the
      theory in their practice. Conclusions We conclude that our model of diagnostic
      clinical epidemiology offers a logical environment for an easy and rapid
      assessment of the evolution of disease probability with consecutive tests,
      providing a scientific format for 'qualitative' clinical estimations.

PMID- 17518803
TI  - New models for old questions: generalized linear models for cost prediction.
AB  - BACKGROUND: Generalized linear models (GLMs) have recently been introduced into
      cost data analysis. GLMs, transformations of the linear regression model, are
      characterized by a particular response distribution from one of the exponential
      family of distributions and monotonic link function which relates the response
      mean to a scale on which additive model effects operate. OBJECTIVES: This study
      compared GLMs and ordinary least squares regression (OLS) in predicting
      individual patient costs in adult intensive care units (ICUs) and sought to
      define the utility of the inverse Gaussian distribution family within GLMs.
      METHODS: A prospective 'ground-up' utilization costing study was performed in
      three adult university associated ICUs, enrolling consecutive ICU admissions over
      a 6-month period in 1991. ICU utilization, patient demographic and ICU admission
      day data were recorded by dedicated data collectors. Model performance was
      assessed by prediction error [mean absolute error (MAE), root mean squared error
      (RMSE)] and residual analysis. RESULTS: The cohort, 1098 patients surviving ICU,
      was of mean (SD) age 56 (19.5) years and 41% female. Patient costs per ICU
      episode (1991 A$) were A$6311 (9689), with range A$106 to A$95602. Prediction
      error for mean costs was minimal (MAE 4780; RMSE 8965) with OLS using
      heteroscedastic retransformation of log costs and GLM with Gaussian family and
      log link (MAE 4798; RMSE 8907). Residual analysis suggested optimal overall
      performance for the above two models and a GLM with inverse Gaussian family and
      log link. CONCLUSIONS: Traditional cost models of OLS with (log) cost
      transformation may be supplemented by appropriately specified GLM which more
      closely model the error structure.

PMID- 17518804
TI  - Distracting communications in the operating theatre.
AB  - RATIONALE AND AIMS: Research suggests that there are problems of communication
      effectiveness in surgery. Here we describe the content, initiators and recipients
      of communications that intrude or interfere with individual surgical cases. We
      also consider the level at which the surgical team and its team members are
      distracted by these case-irrelevant communications (CICs). METHODS: Two
      psychologist observers sampled 48 general surgery procedures and they recorded
      the initiator and the recipient of CIC events, their content and the level of
      observable distraction that they caused. RESULTS: Irrelevant comments and queries
      (i.e. 'small-talk') accounted for half of the observed CICs. From the remaining
      CICs that we observed, most were related to the organization and administration
      of the case-list, to operating theatre provisions and to teaching junior staff.
      Surgeons initiated a third of the observed CICs, while receiving two thirds of
      them. External staff visiting the operating theatre initiated the most
      distracting communications. The CICs addressed to surgeons introduced
      significantly less distraction to the operating theatre than those addressed to
      anaesthetists and nurses. CONCLUSIONS: Some of the observed CICs contributed to
      the administration of the operating theatre case-list. Nonetheless, this
      communication can interfere with highly sensitive work. More effectively co
      ordinated communication could reduce this interference. More research should
      assess the communication effectiveness and the impact of CICs on task performance
      in the operating theatre.

PMID- 17518805
TI  - A survey of the practice of stroke doctors in developing transient ischaemic
      attack services in the UK.
AB  - RATIONALE, AIMS AND OBJECTIVES: (1) To describe current practice in the
      establishment and running of transient ischaemic attack (TIA) clinics in the UK;
      (2) to identify whether TIA targets are met; (3) to inform future TIA service
      development. METHODS: A survey distributed to the members of the British
      Association of Stroke Physicians (BASP). RESULTS: Forty-one per cent of full BASP
      members responded to the survey. TIA clinics were being run by 77% of
      respondents. Of the remainder 75% had plans to do so. Dedicated consultant time
      for stroke predominated among those involved in clinics (87% vs. 54%). The median
      time for clinics operation was 36 months. The median time from TIA to appointment
      was 2 weeks, exceeding national targets. Sixty-four per cent of clinics were run
      weekly and 31% more than once a week. Forty-six per cent stated they ran a one
      stop clinic service yet only 10% said there were no later follow-up visits. A
      patient returning for completion of investigations was the most common reason for
      this (60%). Waits for investigations were reported - 53% indicated a wait for
      carotid Doppler scanning and 41% indicated this wait was in excess of 1 week.
      CONCLUSION: Key areas of concern arising from this survey were that time from TIA
      to clinic appointment remained outside the national target and there were delays
      for key investigations. Current service models are inadequate to meet current TIA
      targets and exploration of alternative service models is required.

PMID- 17518806
TI  - Determining if disease management saves money: an introduction to meta-analysis.
AB  - Disease management (DM) programmes have long been promoted as a major medical
      cost-saving mechanism, even though the scant research that exists on the topic
      has provided conflicting results. In a 2004 literature review, the Congressional
      Budget Office stated that 'there is insufficient evidence to conclude that
      disease management programs can generally reduce the overall cost of health care
      services'. To address this question more accurately, a meta-analysis was
      warranted. Meta-analysis is the quantitative technique used to pool the results
      of many studies on the same topic and summarize them statistically. This method
      is also quite suitable for individual DM firms to assess whether their programmes
      are effective at the aggregate level. This paper describes the elements of a
      rigorous meta-analytic process and discusses potential biases. A hypothetical DM
      organization is then evaluated with a specific emphasis on medical cost-savings,
      simulating a case in which different populations are served, evaluation
      methodologies are employed, and diseases are managed.

PMID- 17518807
TI  - Appropriate utilization of hospital beds in internal medicine: evaluation in a
      tertiary care hospital.
AB  - AIM: To assess the appropriateness of utilization of beds in the internal
      medicine department of a university hospital. METHODS: The appropriateness of
      hospital stay was evaluated using the Appropriateness Evaluation Protocol. A
      random sample of 402 days of stay was assessed. RESULTS: One hundred and thirty
      nine days of stay (34.6%) were classified as inappropriate. The inappropriate
      stays were mostly secondary to hospital-related factors. The two major factors
      for inappropriate stays were 'inappropriate timing/delay in diagnostic
      procedures/consultations' (27%) and 'delay in obtaining test results' (27%). None
      of the factors including age, gender, residence and inpatient period was
      significantly related to inappropriate stay in univariate analysis. CONCLUSION:
      This study indicated that a significant portion of stays were inappropriate.
      Efforts to decrease particularly hospital-related factors associated with
      inappropriate stay are needed.

PMID- 17518808
TI  - Practice patterns of physiotherapists in the treatment of work-related back pain.
AB  - RATIONALE AND OBJECTIVES: Although physiotherapists (PTs) are one of the health
      professionals most involved in the treatment of back pain, their practice
      patterns have not been well studied. The study objectives were to identify the
      practice patterns of PTs treating workers suffering from acute/subacute back
      pain, with and without radiating pain below the knee, and to assess the
      relationship between these patterns and characteristics of PTs. METHODS: PTs
      working in private clinics in the province of Quebec, Canada were invited to
      participate. Each PT used a self-administered questionnaire to record, for each
      treatment session, treatment objectives, interventions used and education given
      to two workers with back pain, one without radiating pain (n = 189 PTs) and one
      with radiating pain (n = 136 PTs). Multiple correspondence analysis with
      hierarchical classification was used to identify practice patterns of PTs.
      Multinomial logistic regressions were used to assess the relationship between
      practice patterns and PTs characteristics. RESULTS: For workers without radiating
      pain, 51.9% of PTs focused their treatment on soft tissue mobilizations/massage
      and heat, 24.3% focused on the McKenzie approach and related interventions, and
      23.8% focused on exercises and function. Similar results were found for workers
      with radiating pain. Most of the PT characteristics were not related to practice
      patterns. CONCLUSIONS: The practices of PTs appeared to be separated into three
      distinct patterns. These practice variations suggest that there may be
      disagreement or uncertainty among PTs in the management of work-related back
      pain. The lack of evidence for the majority of interventions used by PTs and the
      difficulties of integrating evidence into clinical practice may be possible
      explanations.

PMID- 17518809
TI  - Evaluating cardiovascular mortality in type 2 diabetes patients: an analysis
      based on competing risks Markov chains and additive regression models.
AB  - RATIONALE, AIMS AND OBJECTIVES: Type 2 diabetes represents a condition
      significantly associated with increased cardiovascular mortality. The aims of the
      study are: (i) to estimate the cumulative incidence function for cause-specific
      mortality using Cox and Aalen model; (ii) to describe how the prediction of
      cardiovascular or other causes mortality changes for patients with different
      pattern of covariates; (iii) to show if different statistical methods may give
      different results. METHODS: Cox and Aalen additive regression model through the
      Markov chain approach, are used to estimate the cause-specific hazard for
      cardiovascular or other causes mortality in a cohort of 2865 type 2 diabetic
      patients without insulin treatment. The models are compared in the estimation of
      the risk of death for patients of different severity. RESULTS: For younger
      patients with a better covariates profile, the Cumulative Incidence Function
      estimated by Cox and Aalen model was almost the same; for patients with the worst
      covariates profile, models gave different results: at the end of follow-up
      cardiovascular mortality rate estimated by Cox and Aalen model was 0.26 [95%
      confidence interval (CI) = 0.21-0.31] and 0.14 (95% CI = 0.09-0.18). CONCLUSIONS:
      Standard Cox and Aalen model capture the risk process for patients equally well
      with average profiles of co-morbidities. The Aalen model, in addition, is shown
      to be better at identifying cause-specific risk of death for patients with more
      severe clinical profiles. This result is relevant in the development of analytic
      tools for research and resource management within diabetes care.

PMID- 17518810
TI  - Development of explicit criteria for prioritization of hip and knee replacement.
AB  - RATIONALE AND AIMS: Among the problems to the publicly funded national health
      services are the waiting lists. Patients who need elective surgery generally have
      long waiting times before treatment. We aimed to develop a new prioritization
      tool for primary hip and knee replacement. METHODS: Criteria were developed using
      a modified Delphi panel process. We convened a panel of nine members who scored
      the scenarios created by the research team and by patient focus groups. We
      studied the level of agreement among the panelists and the contribution of the
      variables to the ratings of the panel using linear and logistic regression
      models. The priority scores of the variables and their levels were synthesized
      using the optimal scaling and standard linear regression methods. RESULTS: Seven
      variables, pain on motion, walking functional limitations, abnormal findings on
      physical examination, pain at rest, other functional limitations, social role,
      and other pathologies that could improve with joint replacement, were considered
      to create the different scenarios. The panel scored 192 scenarios. The
      disagreement among the panelists was very low (1%) with an intra-class
      correlation coefficient of 0.72. Of the 192 scenarios, 45.8% were scored as
      urgent, 35.4% as preferred and 18.8% as ordinary. The variables that contributed
      most to the scores were pain on motion and walking functional limitations. When
      optimal scaling and regression techniques were applied, similar results were
      obtained. CONCLUSION: This tool can evaluate and prioritize patients on a waiting
      list for hip or knee replacement. We also provide a simple and easy way to use an
      algorithm to estimate the treatment priority for individual patients.

PMID- 17518811
TI  - Family history of mental illness and frequent mental distress in community clinic
      patients.
AB  - OBJECTIVE: The objective of this study was to investigate the importance of
      family history of mental illness as a risk factor for self-reported frequent
      mental distress among patients who use community-based clinics. DESIGN: A cross
      sectional survey was distributed to a convenience sample in three community
      clinics serving largely low-income patients. Forms were completed by 793 clinic
      patients. Multiple logistic regression analysis was to control for the effects of
      demographic variables. RESULTS: In this sample of primary care patients, 27.1%
      had frequent mental distress. Having a family history of mental illness or
      substance abuse was found to be associated with frequent mental distress in this
      population [adjusted odds ratio (OR) = 2.24, P = 0.000]. Also associated with
      increased odds of frequent mental distress were avoiding medical care owing to
      cost (OR = 1.86, P = 0.003) and obesity (OR = 1.73, P = 0.006). CONCLUSIONS:
      Having a family history of mental illness or substance abuse is independently
      associated with increased odds of frequent mental distress among primary care
      patients seen in community clinics. Three strategies are suggested for using this
      information to prevent frequent mental distress: health education via mass
      communication to the general population of primary care patients being followed
      in a clinic, health education to at-risk patients, and targeted screening of
      clinic patients who have the risk factor.

PMID- 17518812
TI  - Cost-effectiveness of an electronic medication ordering and administration system
      in reducing adverse drug events.
AB  - OBJECTIVES: Adverse drug events (ADEs) are common and cause significant morbidity
      and mortality. Patient safety groups advocate the implementation of electronic
      medication order entry systems to reduce ADEs. However, these systems are costly,
      and there are limited data on their effectiveness. We conducted a study to
      examine the costs of introducing an electronic medication ordering and
      administration system and its potential impact on reducing ADEs. METHODS: An
      incremental cost-effectiveness analysis was performed comparing an electronic
      medication ordering and administration system to the standard system used at a
      large health care institution over a 10-year time horizon. Estimates of effect
      were obtained from the literature. Cost data were obtained from a health care
      institution in Toronto, Canada. RESULTS: The incremental cost-effectiveness of
      the new system was $12,700 (USD) per ADE prevented. The cost-effectiveness was
      found to be sensitive to the ADE rate, to the effectiveness of the new system,
      the cost of the system, and costs due to possible increase in doctor workload.
      CONCLUSIONS: An electronic medication order entry and administration system could
      improve care by reducing adverse events. Unfortunately there are limited data on
      effectiveness of these systems at reducing ADEs. Further research is required to
      determine more precisely the potential economic benefit of this technology.

PMID- 17518813
TI  - The role of Clinical Support Workers in reducing junior doctors' hours and
      improving quality of patient care.
AB  - AIM: The aim of the study was to see if the introduction of Clinical Support
      Workers (CSWs) at a teaching hospital could reduce the medical work intensity for
      junior doctors without compromising the quality of patient care. BACKGROUND: The
      'New Deal' and 'European Working Time Directive' have prompted hospitals to take
      a close look at junior doctors' hours and work intensity in order to make posts
      compliant. Following the Department of Health's publication 'reducing junior
      doctors' hours', it was felt that certain clinical duties could be shared with
      nursing staff. METHODS: Two audits were undertaken 8 months apart. The first was
      to determine the areas where the introduction of CSW would make the biggest
      impact. The second was to determine if this impact had had an effect on the
      intensity of work carried out by the junior doctors. FINDINGS: The CSW greatly
      reduced the number of cannulations and venepunctures performed by the doctors
      without any compromise to patient care. RELEVANCE TO CLINICAL PRACTICE: This
      study shows that other allied health professionals can be trained to carry out
      certain tasks that previously were only performed by doctors. This not only
      reduces the impact on junior doctors' hours but can also improve patient care,
      with fewer delays encountered when patients are waiting for a procedure.

PMID- 17518814
TI  - Decision analysis model evaluating the cost-effectiveness of risperidone,
      olanzapine and haloperidol in the treatment of schizophrenia.
AB  - PURPOSE: To evaluate the cost-effectiveness of three antipsychotic medications
      (olanzapine, risperidone and haloperidol) in the treatment of schizophrenia using
      the Positive and Negative Symptom Scale. STUDY DESIGN AND METHODS: A decision
      analysis model was created to evaluate the cost-effectiveness of two atypical
      antipsychotics (risperidone and olanzapine) and haloperidol. Outcome
      probabilities were determined from published clinical trials. The main dependent
      variable of interest was to compare the incremental cost-effectiveness ratios
      (ICER) of the atypical antipsychotic with haloperidol, and also to compare the
      ICER of olanzapine and risperidone. Sensitivity analyses were conducted for
      olanzapine and risperidone to determine the effects of altering drug cost,
      efficacy and re-hospitalization rate on total costs. RESULTS: Risperidone and
      olanzapine were dominant strategies compared with haloperidol (less costly and
      more effective). Risperidone was also dominant when compared with olanzapine. A
      one-way sensitivity analysis for efficacy indicated that the efficacy of
      risperidone would need to decrease by approximately 3% from the base-case in
      order for olanzapine and risperidone to have equal total costs. In a two-way
      sensitivity analysis varying both the cost of olanzapine and risperidone, the
      difference in drug costs between them would have to increase from $2.12 per day
      to $4.12 per day in order to have equal total costs. In terms of varying re
      hospitalization rates, the re-hospitalization rate for risperidone would have to
      increase from 3% to 33% greater than the re-hospitalization rate for olanzapine
      in order to have equal total direct costs. CONCLUSION: Based on this decision
      model, atypical antipsychotics were a dominant strategy over haloperidol
      primarily because of increased efficacy and lower re-hospitalizations. The ICER
      indicated that risperidone was dominant over olanzapine because of lower drug
      costs and increased number of responders, which leads to decreased total costs.

PMID- 17518815
TI  - Can ear swabs help in improving the prescription of ear drops?

PMID- 17518816
TI  - Prognosis following head injury: a survey of doctors from developing and
      developed countries.

PMID- 17518817
TI  - Evolution of a non-transplant hepatobiliary unit.

PMID- 17518818
TI  - Consequences of treatment delay in Lyme disease.

PMID- 17518819
TI  - Primary care doctor attributions for why patients did not receive adequate
      antidepressant treatment.

PMID- 17518820
TI  - Tailoring urological outpatient services to patient choice.

PMID- 17518821
TI  - Lessons from Malinowski: scholarship opportunities and the clinical academic.

PMID- 17518822
TI  - The sustainability of ideals, values and the nursing mandate: evidence from a
      longitudinal qualitative study.
AB  - This article reports on research that examines newly qualified UK nurses'
      experiences of implementing their ideals and values in contemporary nursing
      practice. Findings are presented from questionnaire and interview data from a
      longitudinal interpretive study of nurses' trajectories over time. On
      qualification nurses emerged with a coherent and strong set of espoused ideals
      around delivering high quality, patient-centred, holistic and evidence-based
      care. These were consistent with the current UK nursing mandate and had been
      transmitted and reinforced throughout their 'prequalification' programmes. The
      existence of professional and organisational constraints influenced their ability
      to implement these ideals and values once in practice. Data analysis revealed
      that within 2 years in practice the newly qualified nurses could be categorised
      as sustained idealists, compromised idealists, or crushed idealists. The majority
      experienced frustration and some level of 'burnout' as a consequence of their
      ideals and values being thwarted. This led to disillusionment, 'job-hopping' and,
      in some cases, a decision to leave the profession. These data are explored and
      discussed to inform the question of whether the current nursing mandate is
      sustainable.

PMID- 17518823
TI  - The exodus of health professionals from sub-Saharan Africa: balancing human
      rights and societal needs in the twenty-first century.
AB  - Increased international migration of health professionals is weakening healthcare
      systems in low-income countries, particularly those in sub-Saharan Africa. The
      migration of nurses, physicians and other health professionals from countries in
      sub-Saharan Africa poses a major threat to the achievement of health equity in
      this region. As nurses form the backbone of healthcare systems in many of the
      affected countries, it is the accelerating migration of nurses that will be most
      critical over the next few years. In this paper we present a comprehensive
      analysis of the literature and argue that, from a human rights perspective, there
      are competing rights in the international migration of health professionals: the
      right to leave one's country to seek a better life; the right to health of
      populations in the source and destination countries; labour rights; the right to
      education; and the right to non-discrimination and equality. Creative policy
      approaches are required to balance these rights and to ensure that the individual
      rights of health professionals do not compromise the societal right to health.

PMID- 17518824
TI  - Failures of reproduction: problematising 'success' in assisted reproductive
      technology.
AB  - This paper scrutinises the many ways in which 'success' is portrayed in
      representing assisted reproductive technology (ART) services and illuminates how
      these definitions differ from those held by participant couples. A qualitative
      approach informed by feminist perspectives guided this study and aimed to
      problematise the concept of 'success' by examining literature from ART clinics,
      government reports on ART, and by analysing narratives of couples who have
      accessed ART services. As many ART services have varying definitions of 'success'
      and as statistics are manipulated to promote further patronage of ART services,
      the likelihood of 'success' is often overstated. This paper is concerned with the
      effects this promotion has on the participants. We suggest that this very
      mobilisation of statistical success changes the ability of those who access ART
      services to make productive decisions about themselves inside these treatment
      regimes, as the basis for decision-making is hidden by the way numbers,
      objectivity and clinical reasoning operate to maintain participation in the
      program. In such an operation, the powerful mix of hope and technology kept
      participants enrolled far longer than they originally planned. Moreover, how
      success rates are manipulated raises ethical issues for all involved: clients,
      counsellors, and nursing and medical professionals.

PMID- 17518825
TI  - Experiences of infertility: liminality and the role of the fertility clinic.
AB  - This paper explores the experiences of infertile women who occupy a liminal space
      in society, and argues that the fertility clinic served as a space to tolerate
      women's experiences of liminality. It provided not only rituals aimed at
      transition to pregnancy, but also a space where women's liminal experiences,
      which are caused by the existential chaos of infertility, could be tolerated. The
      British experience seemed to differ from the American one identified in the
      literature, where self-management and peer group support are described as
      strategies used by infertile women to manage infertility. The British women in
      this study did not appear to draw so much on self-management or peer group
      support to deal with their experiences of infertility. They appeared to be
      isolated in their experience. The clinic thus provided a space in which
      recognition was given to their intensely private experiences of difference from
      those in the outside fertile world and allowed them to manage these socially
      unacceptable, culturally taboo and invisible experiences. However, because of its
      very limited success rate in enabling women to become pregnant, rather than
      facilitating the transition of status from infertile to fertile woman, the clinic
      also served to reinforce the liminal experiences of those women who remained
      infertile. Inadvertently, the clinic offered a way of being in limbo while at the
      same time reinforcing the liminal experiences of women.

PMID- 17518826
TI  - 'With woman' philosophy: examining the evidence, answering the questions.
AB  - 'With woman', 'woman centred' and 'in partnership with women' are new terms
      associated with midwifery care in Australia, and the underlying philosophy has
      emerged both as an antidote to the medicalisation of pregnancy and in a bid to
      reacquaint women with their natural capacity to give birth successfully and
      without intervention. A reorientation of midwifery services in the 1990s, a shift
      towards midwifery-led care (MLC) and the subsequent introduction of direct entry
      midwifery programs all contributed to this new direction. Central concepts are a
      focus on the childbearing woman and a valuing of women's experiences. While this
      philosophical re-alignment has been applauded by many midwives in terms of
      maternal empowerment and improved autonomy for midwives, there are nonetheless
      some concerns that, with its emphasis on normality, midwifery-led care is in
      danger of becoming an exclusionary model. Particular concerns include meeting the
      needs of a growing cohort of women, those with 'high risk' pregnancies, and the
      educational adequacy of direct entry midwifery programs. To date, there has been
      no thorough evaluation of this emerging midwifery philosophy in Australia. In
      order to open the debate, this paper aims to initiate a discussion of 'with
      woman' midwifery care as it applies to Australian practice.

PMID- 17518827
TI  - White on whiteness: becoming radicalized about race.
AB  - Race difference and whiteness--key elements in the construction of my cultural
      identity - became a focus of my reflective practice that began over 5 years ago.
      This article reflects critically on the production of white identity from my
      social location as a white nurse. My attention focused on two aspects of
      whiteness: the social location from which I live and learn, and the hegemonic but
      unmarked discourse that informs the knowledge I read and create as a researcher.
      My white identity is characterized by four features: the absent presence of
      whiteness; the need for an oppositional identity; the entitlement of choice and
      subjectivity; and the denial of a dominant position and relation to the
      racialized Other. Exploring these features is critically important at this
      juncture in global and professional history because of the persistence of
      neoliberalism and the popularity of culturalist approaches to diversity.
      Examining the process of my radicalization about race simultaneously calls
      attention to the historiography of ideas about whiteness and race difference and
      the institutionalization of beliefs and practices about race difference that
      continuously reproduce racialized identities and inform collective nursing
      practice and research.

PMID- 17518828
TI  - Decolonising research: a shift toward reconciliation.
AB  - Although awareness of cultural differences that distinguish Indigenous peoples
      has increased worldwide following attention from international human rights
      bodies, Indigenous cultural values have had little influence in shaping research
      agendas or methods of inquiry. Self-determination and reconciliation policies
      have been part of the decolonisation agenda of governments for several decades;
      however, these have not, until recently, been considered of relevance to
      research. Indigenous peoples feel that they are the most studied population in
      Australia, to the point where even the word research arouses feelings of
      suspicion and defensive attitudes. Indigenous people are generally cynical about
      the benefits of research and cautious toward what many perceive to be the
      colonial mentality or 'positional superiority' ingrained in the psyche of western
      researchers. This article examines the characteristics and colonising effects of
      traditional research methods and describes an alternative, decolonising approach.
      Decolonising research methodology is congruent with Indigenous epistemology and
      is guided by the values and research agenda of Indigenous people. The Guidelines
      for ethical conduct in Aboriginal and Torres Strait islander health research,
      developed by the National Aboriginal and Islander Health Organisation (NAIHO)
      with the National Health & Medical Research Council (NHMRC) in 2003 are examined,
      as they exemplify a decolonising paradigm for researchers.

PMID- 17518829
TI  - Verbal and social interactions in the nurse-patient relationship in forensic
      psychiatric nursing care: a model and its philosophical and theoretical
      foundation.
AB  - The present paper focuses on the nurse-patient relationship in forensic
      psychiatric care. From research in the field six categories of nurse-patient
      interactions are identified: 'building and sustaining relationships',
      'supportive/encouraging interactions', 'social skills training', 'reality
      orientation', 'reflective interactions' and 'practical skills training'. The
      content of each category of interaction in the context of forensic psychiatric
      care is described. A conceptual model is presented together with an empirical,
      philosophical and theoretical foundation for the use of verbal and social
      interactions in nurse-patient interactions in forensic psychiatric nursing care.
      The implications and possible uses of the model in the practical field of
      forensic psychiatric care are discussed.

PMID- 17518830
TI  - Family and medicine.

PMID- 17518831
TI  - Research on problem-based learning: the need for critical analysis of methods and
      findings.

PMID- 17518832
TI  - Jigsaws and the march of time.

PMID- 17518833
TI  - Unannounced standardised patients in real practice: a systematic literature
      review.
AB  - BACKGROUND: No attempt has been made to give a systematic overview of the
      innovative use of unannounced or incognito standardised patients. OBJECTIVE: To
      provide a systematic overview of all published studies with incognito
      standardised patients assessing doctors in actual practice situations using sound
      reliable and valid standardised patient methodology. METHODS: Systematic
      literature search in Medline, Eric and Psyclit with piloted search terms,
      followed by retrieving additional papers from reference lists. All papers were
      scored with a predefined protocol-sheet using predefined inclusion and exclusion
      criteria. RESULTS: Forty papers referring to 21 projects with incognito
      standardised patients were found and described in detail. The majority of studies
      were conducted in primary care and were descriptive. DISCUSSION: There is a need
      for research on the additional value of the incognito standardised patient
      methodology and for a consensus on how to report on accuracy and consistency of
      standardised patients.

PMID- 17518834
TI  - Clinical experience and examination performance: is there a correlation?
AB  - CONTEXT: The Liaison Committee on Medical Education (LCME) requires there to be:
      '...comparable educational experiences and equivalent methods of evaluation
      across all alternative instructional sites within a given discipline'. It is an
      LCME accreditation requirement that students encounter similar numbers of
      patients with similar diagnoses. However, previous empirical studies have not
      shown a correlation between the numbers of patients seen by students and
      performance on multiple-choice examinations. OBJECTIVE: This study examined
      whether student exposure to patients with specific diagnoses predicts performance
      on multiple-choice examination questions pertaining to those diagnoses. METHODS:
      The Department of Pediatrics at the University of Nebraska Medical Center has
      collected patient logbooks from clerks since 1994. These contain information on
      patient demographics and students' roles in patient care. During week 7 of an 8
      week course, students took an examination intended to help them prepare for their
      final examination. Logbooks and pre-examination questions were coded using
      standard ICD-9 codes. Data were analysed using Minitab statistical software to
      determine dependence between patient encounters and test scores. Subjects
      comprised a convenience sample of students who completed the clerkship during
      1997-2000. RESULTS: Our analysis indicates that performance on a multiple-choice
      examination is independent of the number of patients seen. CONCLUSIONS: Our data
      suggest knowledge-based examination performance cannot be predicted by the volume
      of patients seen. Therefore, too much emphasis on examination performance in
      clinical courses should be carefully weighed against clinical performance to
      determine the successful completion of clerkships.

PMID- 17518835
TI  - The effects of examination stress on the performance of emergency medicine
      residents.
AB  - CONTEXT: Despite the finding that residents are exposed to significant stressors
      during their training, little is known about the impact of these stressors on
      performance. The objectives of this project were to measure the subjective
      anxiety felt by emergency medicine (EM) residents during in-training
      examinations, and to determine the effect of this anxiety on their ability to
      diagnose visual stimuli such as X-rays, photographs and electrocardiographs.
      METHODS: Two examinations, matched for difficulty and length, were constructed
      based on the performance of 23 residents in 2 Royal College of Physicians and
      Surgeons of Canada (RCPSC) EM residency programmes. These examinations were then
      administered at 2-week intervals to another 24 residents in 2 additional RCPSC EM
      programmes. One examination was administered under high-stress conditions (in
      training examination) and the other under low-stress (control) conditions.
      Perceived anxiety was measured using the state scale of the State-Trait Anxiety
      Inventory before and after each iteration of the examination. RESULTS: Residents
      reported higher levels of anxiety in the high-stress condition (41.5 versus 35.9,
      P < 0.05). Examination scores were higher in the high-stress condition (70.4
      versus 64.4, P < 0.01). The scores of junior residents improved in the high
      stress condition, whereas those of intermediate and senior residents did not
      change. CONCLUSIONS: Emergency medicine residents report higher anxiety during in
      training examinations compared with control conditions. Residents at all levels
      exhibited similar perceptions of anxiety. Junior residents performed better under
      stress, achieving higher scores during the in-training examination than during
      the control condition. The performance of more experienced residents was not
      affected by the stress condition.

PMID- 17518836
TI  - What is the educational impact of standards-based assessment in a medical degree?
AB  - CONTEXT: Many medical courses use standards-based assessment, usually reported by
      a restricted range of categories, but there is little evidence of its educational
      impact. This study aimed to evaluate the impact on medical student learning of
      changing to standards-based assessments reported by distinction, pass or fail.
      METHODS: We carried out a prospectively planned before-and-after study within an
      undergraduate medical course using a questionnaire to compare motivation and
      approaches to the study, and a diary to compare the number of hours spent
      studying. RESULTS: Questionnaire response rates were 607/752 (81%) before the
      change and 651/780 (83%) afterwards. Daily diary response rates were 1074/1478
      (73%) before, and 1304/1844 (71%) after the change. Deep motive declined with
      class year during norm-referenced assessments but not with standards-based
      assessment (r = - 0.11 versus 0.01; P < 0.02). Deep strategy increased
      significantly under standards-based assessments in students in Years 2 and 3
      (mean difference 0.64 [0.08-1.2]; P < 0.05) and Year 6 (mean difference 2.0 [0.03
      3.9]; P < 0.05). Competitiveness scores declined as students progressed through
      the course in both cohorts. Students identified themselves as feeling more like a
      doctor after the change to standards-based assessments. Time spent studying was
      largely unchanged but the proportions of wanted discretionary study increased
      from 64% to 71% for students in Years 2 and 3, and from 65% to 70% for students
      in Years 4 and 5. CONCLUSIONS: The changes were associated with beneficial
      effects on deep motive, deep strategy, professional identify and intrinsically
      motivated study. There were no changes in competitiveness and minimal changes in
      amount of time spent studying.

PMID- 17518837
TI  - Assessment of non-cognitive traits through the admissions multiple mini
      interview.
AB  - CONTEXT: Contemporary studies have shown that traditional medical school
      admissions interviews have strong face validity but provide evidence for only low
      reliability and validity. As a result, they do not provide a standardised,
      defensible and fair process for all applicants. METHODS: In 2006, applicants to
      the University of Calgary Medical School were interviewed using the multiple mini
      interview (MMI). This interview process consisted of 9, 8-minute stations where
      applicants were presented with scenarios they were then asked to discuss. This
      was followed by a single 8-minute station that allowed the applicant to discuss
      why he or she should be admitted to our medical school. Sociodemographic and
      station assessment data provided for each applicant were analysed to determine
      whether the MMI was a valid and reliable assessment of the non-cognitive
      attributes, distinguished between the non-cognitive attributes, and discriminated
      between those accepted and those placed on the waitlist (waiting list). We also
      assessed whether applicant sociodemographic characteristics were associated with
      acceptance or waitlist status. RESULTS: Cronbach's alpha for each station ranged
      from 0.97-0.98. Low correlations between stations and the factor analysis suggest
      each station assessed different attributes. There were significant differences in
      scores between those accepted and those on the waitlist. Sociodemographic
      differences were not associated with status on acceptance or waiting lists.
      DISCUSSION: The MMI is able to assess different non-cognitive attributes and our
      study provides additional evidence for its reliability and validity. The MMI
      offers a fairer and more defensible assessment of applicants to medical school
      than the traditional interview.

PMID- 17518838
TI  - Undergraduate medical students: who seeks formative feedback?
AB  - OBJECTIVE: This study aimed to monitor which undergraduate students collected
      formative feedback on their degree essays and to quantify any correlations
      between gender or summative mark achieved and whether formative feedback was
      sought. METHODS: We carried out a study at the University of Aberdeen Medical
      School, involving a total of 360 Year 3 students, comprising all 177 students in
      the 2004 cohort and 183 in 2005. Data on gender and summative mark were routinely
      collected during the degree assessment processes in March 2004 and 2005. Students
      signed on receipt of their feedback. RESULTS: Less than half the students (46%)
      collected their formative feedback: 47% in 2004, and 45% in 2005. Overall,
      females were significantly more likely than males to seek formative feedback (P =
      0.004). Higher achievers were significantly more likely than lower achievers to
      seek their feedback (P = 0.020). CONCLUSIONS: Our findings indicate that these
      medical students, particularly males and poor students, may not use assessment
      feedback as a learning experience. Female and better students are keener to seek
      out formative feedback that might be expected to help them continue to do well.
      We need to explore further why so many students do not access formative feedback,
      and develop strategies for addressing this issue effectively.

PMID- 17518839
TI  - Challenges in multisource feedback: intended and unintended outcomes.
AB  - CONTEXT: Multisource feedback (MSF) is a type of formative assessment intended to
      guide learning and performance change. However, in earlier research, some doctors
      questioned its validity and did not use it for improvement, raising questions
      about its consequential validity (i.e. its ability to produce intended outcomes
      related to learning and change). The purpose of this qualitative study was to
      increase understanding of the consequential validity of MSF by exploring how
      doctors used their feedback and the conditions influencing this use. METHODS: We
      used interviews with open-ended questions. We purposefully recruited volunteer
      participants from 2 groups of family doctors who participated in a pilot
      assessment of MSF: those who received high (n = 25) and those who received
      average/lower (n = 44) scores. RESULTS: Respondents included 12 in the higher-
      and 16 in the average/lower-scoring groups. Fifteen interpreted their feedback as
      positive (i.e. confirming current practice) and did not make changes. Thirteen
      interpreted feedback as negative in 1 or more domains (i.e. not confirming their
      practice and indicating need for change). Seven reported making changes. The most
      common changes were in patient and team communication; the least common were in
      clinical competence. Positive influences upon change included receiving specific
      feedback consistent with other sources of feedback from credible reviewers who
      were able to observe the subjects. These reviewers were most frequently patients.
      DISCUSSION: Findings suggest circumstances that may contribute to low
      consequential validity of MSF for doctors. Implications for practice include
      enhancing procedural credibility by ensuring reviewers' ability to observe
      respective behaviours, enhancing feedback usefulness by increasing its
      specificity, and considering the use of more objective measures of clinical
      competence.

PMID- 17518840
TI  - Qualitative assessment of the long-term impact of a faculty development programme
      in teaching skills.
AB  - CONTEXT: The long-term impact of faculty development programmes (FDPs) is poorly
      understood, and most assessments of them have been quantitative in nature.
      OBJECTIVE: This study aimed to use qualitative methods to better understand the
      long-term impact of an FDP in teaching skills (FDP/TS). METHODS: A survey was
      carried out in July 2002 of the 242 faculty members and fellows who had
      participated in a 9-month FDP/TS at any time from 1987 through 2000. The survey
      included 2 quantitative questions and an open-ended qualitative question about
      the impact of the programme on the participants' professional and personal lives.
      RESULTS: A total of 200 past participants (83%) responded to the survey.
      Participants from early and recent cohorts were similarly represented. In all,
      82% of respondents said programme participation had had 'a moderate' or 'a lot'
      of impact on their professional life, and 49% said their personal life had been
      affected to this degree. Four major domains, each containing at least 3
      subcategories, emerged from qualitative analysis. The domain intrapersonal
      development included changes participants reported in themselves and in their
      approach to self-management. Interpersonal development contained subcategories
      relating to how participants interact with others. Subcategories in the domain
      development as a teacher related to increased teaching ability and enjoyment. The
      domain career development included professional growth and career opportunities
      attributed to programme participation. CONCLUSIONS: Longitudinal FDPs can have
      broad and sustained positive effects on the professional and personal lives of
      participants. Qualitative evaluation methods may result in a richer and deeper
      understanding of the impact of these programmes.

PMID- 17518841
TI  - 'Flying below the radar': a qualitative study of minority experience and
      management of discrimination in academic medicine.
AB  - OBJECTIVES: This paper aims to give voice to the lived experience of faculty
      members who have encountered racial or ethnic discrimination in the course of
      their academic careers. It looks at how they describe the environment for
      minorities, how they manage discrimination and what institutions and majority
      member faculty can do to improve medical academe for minority members. METHODS:
      Qualitative techniques were used for semi-structured, in-depth individual
      telephone interviews, which were audiotaped, transcribed and analysed by
      reviewers. Themes expressed by multiple faculty members were studied for patterns
      of connection and grouped into broader categories. A description of the faculty
      sample is provided, in which respondents ranked the importance of discrimination
      in hindering academic advancement and used Likert scales to evaluate effects of
      discrimination. The sample was drawn from 12 of 24 academic medical centres in
      the National Faculty Survey and included 18 minority-member faculty staff
      stratified by gender, rank and degree who had experienced, or possibly
      experienced, work-related discrimination. RESULTS: Minority faculty described the
      need to be strongly self-reliant, repeatedly prove themselves, develop strong
      supports and acquire a wide range of academic skills to succeed. Suggested
      responses to discrimination were to be cautious, level-headed and informed.
      Confronting discriminatory actions by sitting down with colleagues and raising
      the level of awareness were important methods of dealing with such situations.
      CONCLUSIONS: Academic medical centres may need to make greater efforts to support
      minority faculty and improve understanding of the challenges confronting such
      faculty in order to prevent the loss and/or under-utilisation of important
      talent.

PMID- 17518842
TI  - Teaching professionalism in the early years of a medical curriculum: a
      qualitative study.
AB  - CONTEXT: Despite the growing literature on professionalism in undergraduate
      medical curricula, few studies have examined its delivery. OBJECTIVES: This study
      investigated tutors' and students' perspectives of the delivery of
      professionalism in the early years of Glasgow's learner-centred, problem-based
      learning (PBL), integrated medical curriculum. METHODS: A qualitative approach
      was adopted involving semistructured interviews, on a 1 in 6 sample of tutors
      involved in teaching in the early curricular years, and 3 student focus groups.
      The findings were subjected to between-method triangulation. RESULTS: Involvement
      in teaching raised students' and tutors' awareness of their professionalism.
      Learning activities promoting critical reflection were most effective. The
      integration of professionalism across the domains of Vocational Studies (VS) was
      important for learning; however, it was not well integrated with the PBL core.
      Integration was promoted by having the same tutor present throughout all VS
      sessions. Early patient contact experiences were found to be particularly
      important. The hidden curriculum provided both opportunities for, and threats to,
      learning. The small-group format provided a suitable environment for the
      examination of pre-existing perspectives. The portfolio was an effective learning
      tool, although its assessment should be formalised. CONCLUSIONS: Reflection is
      integral to professional development. Early clinical contact is an important part
      of the process of socialisation, as it allows students to enter the community of
      practice that is the medical profession. Role models can contribute powerfully to
      students' learning and identity formation. As students move towards fuller
      participation, the clinical milieu should be controlled to maximise the influence
      of role models, and opportunities for guided reflection should be sustained.

PMID- 17518843
TI  - Learning styles: do they really exist?

PMID- 17518844
TI  - Re: the impact of simulation on people who act as simulated patients: a focus
      group study.

PMID- 17518845
TI  - The process of learning during an examination.

PMID- 17518847
TI  - Introduction: reflections on emerging technologies at the centennial of organ
      transplantation.

PMID- 17518848
TI  - The god squad and the origins of transplantation ethics and policy.
AB  - The era of replacing human organs and their functions began with chronic dialysis
      and renal transplantation in the 1960s. These significant medical advances
      brought unprecedented problems. Among these, the selection of patients for a
      scarce resource was most troubling. In Seattle, where dialysis originated, a "God
      Committee" selected which patients would live and die. The debates over such a
      committee stimulated the origins of bioethics.

PMID- 17518849
TI  - The use of nonhuman animals in biomedical research: necessity and justification.
AB  - Discourse about the use of animals in biomedical research usually focuses on two
      issues: its empirical and moral use. The empirical issue asks whether the use of
      nonhumans in experiments is required in order to get data. The moral issue asks
      whether the use of nonhumans can be defended as matter of ethical theory.
      Although the use of animals in research may involve a plausible necessity claim,
      no moral justification exists for using nonhumans in situations in which we would
      not use humans.

PMID- 17518850
TI  - Markets in health care: the case of renal transplantation.
AB  - This article explores the ethics and economics of a market in donated kidneys in
      the United States. With the impending changes in the health care system, the
      author argues that a full turn to the market for distribution of kidneys is not
      appropriate. However, he would sanction a regulated market, as outlined in the
      article.

PMID- 17518851
TI  - The injustice of enforced equal access to transplant operations: rethinking
      reckless claims of fairness.
AB  - The globalizing or totalizing imposition of a particular understanding of
      justice, fairness, or equality, as seen, for example, in Canada's single health
      care system, which forbids the sale of private insurance and the purchase of
      better basic health care, cannot be justified in general secular terms because of
      the following limitations: (1) the plurality of understandings of justice,
      fairness, and equality, and (2) the inability to establish one understanding as
      canonical. The secular state lacks plausible moral authority for the coercive
      imposition of one such account on peaceable, consenting adults. This state of
      affairs, with regard to the weakness of human moral epistemological powers, means
      that the secular state fails to have the moral authority to forbid coercively the
      sale and purchase of organs. It further lacks the secular, moral authority to
      impose equal access to organ transplantations. Assertions of such authority
      amount to reckless claims of fairness, and for this reason, health care policy
      must be set within the constraints of limited, constitutional regimes.

PMID- 17518852
TI  - Clinical trials of xenotransplantation: waiver of the right to withdraw from a
      clinical trial should be required.
AB  - Xenotransplantation pits clinical research ethics against public health needs
      because recipients must undergo long-term, perhaps life-long, surveillance for
      infectious diseases. This surveillance requirement is effectively an abrogation
      of the right to withdraw from a clinical trial. Ulysses contracts, which are
      advance directives for future care, may be an ethical mechanism by which to
      balance public health needs against limitation of individual rights.

PMID- 17518853
TI  - Brain death - too flawed to endure, too ingrained to abandon.
AB  - The concept of brain death has become deeply ingrained in our health care system.
      It serves as the justification for the removal of vital organs like the heart and
      liver from patients who still have circulation and respiration while these organs
      maintain viability. On close examination, however, the concept is seen as
      incoherent and counterintuitive to our understandings of death. In order to
      abandon the concept of brain death and yet retain our practices in organ
      transplantation, we need to either change the definition of death or no longer
      maintain a commitment to the dead donor rule, which is an implicit prohibition
      against removing vital organs from individuals before they are declared dead.
      After exploring these two options, the author argues that while new definitions
      of death are problematic, alternatives to the dead donor rule are both ethically
      justifiable and potentially palatable to the public. Even so, the author
      concludes that neither of these approaches is likely to be adopted and that
      resolution will most probably come when technological advances in immunology
      simply make the concept of brain death obsolete.

PMID- 17518854
TI  - Genetic determinism and discrimination: a call to re-orient prevailing human
      rights discourse to better comport with the public implications of individual
      genetic testing.
AB  - Genetic testing can not only provide information about diseases but also their
      prevalence in ethnic, gender, or other vulnerable populations. While offering the
      promise of significant therapeutic benefits and serving to highlight our
      commonality, genetic information also raises a number of sensitive human rights
      issues touching on identity and the perception thereof, as well as the
      possibility of discrimination and social stigma. It stands to reason that the
      results of individual screenings could haplessly be used to make general
      assumptions about entire ethnic or gender groups. In this manner, genetic
      information can directly influence identity by impacting and perhaps even
      reframing conceptions of group rights and dimensions of self-identification, thus
      importing constitutional scrutiny on questions of dignity and discrimination in
      particular. Is there a risk of collective stigmatization deriving from discrete
      testing of self-identified individuals? Would such stigmatization impinge on
      individual dignity by the exogenous imposition of ethnic or gender/sexual
      identity? If so, what norms can most adequately respond if and when individual
      and group interests diverge? These questions are examined from a comparative
      perspective.

PMID- 17518855
TI  - Ethics of population-based research.
AB  - This paper considers the morally relevant ways in which population-based research
      is a distinct type of human subjects research that have unique moral
      considerations relevant for public health practitioners and researchers. By
      defining population-based research, the authors distinguish it from public health
      practice and then consider, in more detail, the ways in which population-based
      research differs from clinical human subjects research. Based upon the
      distinctions between these types of research and practice, they identify five
      important issues that arise in the design and conduct of certain kinds of
      population-based research. The authors hope that public health practitioners find
      these distinctions useful in determining when their work may actually be
      population-based research and that public health researchers use them to identify
      the areas where ethical issues in their research may arise.

PMID- 17518856
TI  - Ethics, law, and commercial surrogacy: a call for uniformity.
AB  - In the United States at this time, no uniform federal law exists regarding
      commercial surrogacy, and state statutory schemes vary vastly, ranging from
      criminalization to legal recognition with contract enforcement. The authors
      examine how commercial surrogacy agencies utilize the Internet as a means for
      attracting parents and surrogates by employing emotional cultural rhetoric. By
      inducing both parents and surrogates to their jurisdiction, agencies circumvent
      vast discrepancies in state statutory regulative schemes and create a distinct
      interstate business, absent an efficient regulatory framework or legal recourse
      in some circumstances. The authors propose a uniform federal regulatory scheme
      premised upon regulating interstate business transactions to create
      accountability and legal remedies for both the parents and the surrogate.

PMID- 17518857
TI  - Use of forensic DNA evidence in prosecutors'offices.
AB  - This article reports on a survey of DNA-related practices and procedures within
      District Attorneys' offices to obtain preliminary information about actual
      prosecutorial practices. The data obtained is preliminary but supportive of
      further study of areas targeted by the survey.

PMID- 17518858
TI  - Currents in contemporary ethics. The implications of expanding access to
      unapproved drugs.

PMID- 17518859
TI  - The ethical health lawyer. Loopholes: opportunity, responsibility or liability?

PMID- 17518860
TI  - Abortion distortion: a review of dispelling the myths of abortion history by
      Joseph W. Dellapenna.

PMID- 17518861
TI  - Recent developments in health law. States lead the way on health insurance
      reform.

PMID- 17518864
TI  - Predictors of psychosocial adjustment in people with physical disease.
AB  - AIMS: The purpose of this paper was to examine the demographic, medical and
      psychosocial variables that result in the deterioration of psychosocial
      adjustment in patients with physical disease, the meaning their illness has for
      them and their coping style. METHODS: The study was carried out in inpatient
      clinics of the Istanbul Faculty of Medicine (n = 198). The following evaluation
      instruments were used: a semi-structured questionnaire, the Psychosocial
      Adjustment to Illness Scale-Self Report (PAIS-SR), the Meaning of Illness
      Questionnaire (MIQ), the Hospital Anxiety-Depression Scale, the Multivariate
      Perceived Social Support Questionnaire and the Ways of Coping Inventory (WCI).
      Variables to be related with psychosocial adjustment were analysed by using
      Forward Logistic Regression. RESULTS: The mean age of patients was 36.9 (SD 12.9)
      (18-65), 55% of which were women, the average PAIS-SR score was 1.02 (SD 0.41)
      (0.7-2.26); 47% of the patients had poor adjustment scores. Univariate analysis
      showed that psychosocial adjustment was affected by having children (p = 0.02),
      anxiety, depression, locus of control, perceived social support (p < 0.001),
      information level about their illness and its treatment (p = 0.01), the subscales
      of WCI [escape-avoidance (p < 0.001), distancing (p = 0.002), planned problem
      solving (p < 0.001), positive re-appraisal (p = 0.02)]. The psychosocial
      adjustment of patients with respiratory or infectious illnesses or bone-muscle
      skeletal disorders was even less (p = 0.03). All 33 items of the MIQ were found
      to have a significant impact on psychosocial adjustment (p < 0.001). According to
      the regression analysis, the best predictors of psychosocial adjustment were:
      depression (p < 0.001) and the meaning of illness for patient (p < 0.01).
      CONCLUSIONS: Having a physical illness is an important stress factor. In
      providing assistance, a number of factors should be taken into consideration,
      including how the patient perceives his illness, the impact the illness has on
      the patient's life, and a determination of the degree of depression being
      experienced by the patient. RELEVANCE TO CLINICAL PRACTICE: The study indicated
      some predictors in the assessment of psychosocial adjustment and care of patients
      with physical illness. In daily clinical practice, among the patients with
      physical illness, those with a negative perception of their illness and those who
      define depression should be given special attention for psychosocial support.

PMID- 17518865
TI  - Young women with diabetes: using Internet communication to create stability
      during life transitions.
AB  - AIMS AND OBJECTIVES: The aim of the current study was to explore and describe the
      strategies young women with Type 1 diabetes used to manage transitions in their
      lives. This paper will describe one aspect of the findings of how women with Type
      1 diabetes used the Internet to interact with other people with diabetes and
      create stability in their lives. BACKGROUND: Individuals living with diabetes
      develop a range of different strategies to create stability in their lives and
      enhance their well-being. Changing social and emotional conditions during life
      transitions have a major impact on diabetes management. Although the literature
      indicates that strategies enabling the individuals to cope with transitions are
      important, they remain under-researched. DESIGN: Using grounded theory,
      interviews were conducted with 20 women with Type 1 diabetes. Constant
      comparative data analysis was used to analyse the data and develop an
      understanding of how young women with Type 1 diabetes used the Internet to create
      stability in their lives. FINDINGS: The findings revealed that the women valued
      their autonomy and being in control of when and to whom they reveal their
      diabetic status, especially during life transitions and at times of uncertainty.
      However, during these times they also required health and social information and
      interacting with other people. One of the women's main strategies in managing
      transitions was to use Internet chat lines as a way of obtaining information and
      communicating with others. This strategy gave women a sense of autonomy, enabled
      them to maintain their anonymity and interact with other people on their own
      terms. CONCLUSIONS: Having meaningful personal interactions, social support and
      being able to connect with others were fundamental to the women's well being.
      Most importantly, preserving autonomy and anonymity during such interactions were
      integral to the way the women with Type 1 diabetes managed life transitions.
      RELEVANCE TO CLINICAL PRACTICE: Health professionals need to explore and
      incorporate Internet communication process or anonymous help lines into their
      practice as a way to assist people manage their diabetes.

PMID- 17518866
TI  - Attributing recovery from depression. Perceptions of people cared for in primary
      care.
AB  - AIMS AND OBJECTIVES: The aim of the study was to understand how people treated
      for depression in primary care perceived the care they received. The focus was
      specifically on ascertaining their perceptions of what had helped during their
      treatment, their understanding of the factors to which they attributed their
      recovery, and their reflections on their experience of depression. BACKGROUND:
      Although knowledge of the factors that promote recovery from depression is
      growing, personal accounts of attributions of recovery are largely absent from
      the literature. Identifying and understanding people's accounts of their recovery
      is particularly important for practitioners involved in medication management and
      prescribing. METHOD: A purposeful sample of 60 people who had accessed primary
      care and been prescribed medication because of depressive symptoms was
      interviewed using a semistructured approach. Interviews explored people's
      experiences of accessing and using primary care, their assessments of care
      offered, experiences of medication management and their attributions of recovery.
      RESULTS: Recovery from depression was characterized by its multifactorial nature,
      and two-thirds of the participants felt that medication had contributed to their
      recovery. Factors in recovery changed with the passage of time and many perceived
      personal strengths as important to recovery. Practitioners who acknowledged and
      encouraged people's roles in recovery and supported multifaceted care were
      perceived by users as caring and offering holistic, individualized care.
      CONCLUSION: People with depression are keen to regard their recovery as
      multifactorial and to have their own roles in recovery acknowledged. Preferences
      for a 'portfolio' of care, the components of which change as recovery progresses,
      were evident. RELEVANCE TO CLINICAL PRACTICE: Practitioners involved in
      prescribing and medication management for depression must aim to explore
      patients' beliefs about appropriate treatments and recovery. Addressing these can
      potentially promote treatment concordance and enhance recovery from depression by
      establishing and sustaining therapeutic relationships.

PMID- 17518867
TI  - Non-finite loss and emotional labour: family caregivers' experiences of living
      with motor neurone disease.
AB  - AIM AND OBJECTIVES: This paper aims to add to nurses' knowledge concerning the
      losses and emotional labour family caregivers face caring for people living with
      neurodegenerative, life-limiting illnesses such as motor neurone disease.
      BACKGROUND: Motor neurone disease is a relentless, progressive illness resulting
      in progressive loss of voluntary muscle mass and function. Previous caregiver
      research presents the salient losses such as social, financial and relationship
      loss. However, the non-finite, unpredictable losses faced every day by caregivers
      and the emotional labour experienced are not effectively represented and have not
      been explored for caregivers of adult patients with life-limiting, degenerative,
      illness. DESIGN/METHODS: Semi-structured interviews, ecomaps of social support
      networks and field notes were used to collect data for this ethnographic case
      study. Data were attained at three time points over a 10-month period from 18
      primary caregivers and once from six peripheral caregivers. RESULTS: Data
      revealed new information about the psychosocial and emotional losses experienced
      daily, when living with motor neurone disease. The impact of the constancy of
      voluntary muscle degeneration and the uncertainty of the illness progression in
      terms of available time and functional loss, threatened people's understanding
      and expectations of life, their relationships, their personal identity and their
      future. Managing their relationship with the patient and their reactions to the
      devastation of motor neurone disease is consistent with the concept of emotional
      labour. CONCLUSIONS: Family caregivers living with relentless, life-limiting
      illness experience non-finite losses and emotional labour on a daily basis. While
      each individual's experience of loss is unique, nurses need to include caregivers
      as well as patients, in their spectrum of supportive care. RELEVANCE TO CLINICAL
      PRACTICE: Nurses can be independent confidants who share the emotional labour and
      work with caregivers to develop interventions to assist them to manage their
      losses and their changing needs for psychological and emotional support.

PMID- 17518868
TI  - The relationship between disability and self-care agency of Turkish people with
      rheumatoid arthritis.
AB  - AIM: This study aims to determine the relationship between disability levels and
      self care agency scores in Turkish patients with rheumatoid arthritis and to
      investigate the factors affecting them. BACKGROUND: Self-care agency is the
      complex acquired ability to meet one's constant requirements for care that
      regulates life processes, maintains or promotes the integrity of human structure,
      functioning and development, and promotes well-being. DESIGN AND METHODS: Forty
      three consecutive patients with Rheumatoid Arthritis (M/F: 11/32; mean age 49.53
      +/- 13.37 years; disease duration 118.32 +/- 76.55 months), being followed up by
      Ege University Rheumatology Outpatient Department and all fulfilling ACR 1987
      criteria were included in this study. Data collection instruments used in this
      study were Informative-Demographic Data Form, Health Assessment Questionnaire
      (including disability index and pain scale) and Self-as-Carer Inventory. RESULTS:
      The mean disability index, the mean pain score and the mean self-care agency
      score of patients were 0.53 (SD 0.45), 1.48 (SD 0.74) and 80.95 (SD 27.80) were
      respectively. Self-care agency of patients found moderate level. It was found
      that a positive correlation between the disability index and the self-care agency
      scores (r = 0.488; p < 0.01). It was found that in male (t = 0.907; p = 0.000),
      in patients graduate from university (F = 0.271; p = 0.001), the self-care agency
      was better than other patients. CONCLUSION: In conclusion we found that in
      Turkish patients with Rheumatoid Arthritis, the higher the disability rate was,
      the lower the self-care agency score was. RELEVANCE TO CLINICAL PRACTICE:
      Disability, pain and their impact on self-care agency should be focused on in
      everyday care for Rheumatoid Arthritis patients. These areas are most important
      in nursing care and should be considered while organizing the medical treatment
      and rehabilitation programme.

PMID- 17518869
TI  - 'Doing dialysis at home': client attitudes towards renal therapy.
AB  - AIM: This paper reports a study seeking to describe characteristic attitudes
      towards their treatment regime among a group living on home dialysis. BACKGROUND:
      Although there are many papers about the problem of renal patient compliance and
      a number describing the experience of living on dialysis, studies have not
      focused on client attitudes towards their therapy. METHODS: The study used an
      interpretivist methodology. Twenty home dialysis clients from one renal service
      were interviewed for an hour each in 2004. Texts of the taped interviews were
      analysed to formulate a number of themes that summarize the client perspective.
      RESULTS: During the initial period of adjustment to treatment many participants
      learned their need for treatment by experimenting with the therapeutic
      prescription. They then used their knowledge of the therapy to alter their
      treatment regime to maintain their normal lifestyle. Having modified their
      therapeutic prescription, participants' motivation to continue meeting the
      continuing demands of the treatment regime was influenced by their individual
      life situation, including their relationships, work and personal attitudes
      towards life. CONCLUSION: Health professionals have interpreted renal client
      behaviour in relation to their therapy in terms of compliance, because
      effectiveness of treatment depends on their cooperation. From a client
      perspective their attitudes are better understood in terms of negotiation. Renal
      clients do not simply follow professional advice but, through a process of
      negotiation, seek to integrate therapy into their pattern of regular activities
      to maintain their normal lifestyle. Renal clients' motivation to meet the ongoing
      demands of treatment is not related solely to their health status, but is
      affected by their general life situation. RELEVANCE TO CLINICAL PRACTICE:
      Understanding client attitudes towards therapy enables nurses to support people
      living on dialysis better. Through enhancing their relationships with clients,
      nurses can assume a key role in service to people living with chronic conditions.

PMID- 17518870
TI  - Difficult asthma: people's perspectives on taking corticosteroid therapy.
AB  - AIMS AND OBJECTIVES: This study aimed to explore the experiences of patients with
      difficult asthma, who take corticosteroid therapy, and provide insight into why
      some patients comply with therapy, whilst others do not. BACKGROUND: Asthma is
      growing in prevalence and affects more than 100 million people worldwide.
      Corticosteroids are the mainstay treatment but, despite considerable risk to the
      individual in terms of morbidity and mortality, compliance is low. Previous
      research has been mainly quantitative and analysed variables associated with
      compliance, doing little to increase professional understanding of the patient's
      perspective on taking corticosteroid treatment. METHODS: A hermeneutic
      phenomenological approach was selected as most appropriate for this study.
      Unstructured interviews were undertaken with a purposive sample of 10
      participants. Interviews were taped, transcribed and the data were analysed using
      a multi-step technique described by Holloway. FINDINGS: Fear of side effects was
      the strongest theme to emerge; illustrated by the negative images participants
      described such as weight gain, anxiety, irritability and depression. Participants
      related control and power over their condition to knowledge and information. They
      wanted more information, but believed that health professionals assumed they were
      already well informed. Costs and benefits of treatment were weighed up before
      decisions were made. Participants described feelings of 'not being themselves'
      and personality changes resulting in the loss of their role within relationships.
      Routine, time and opinions of significant others, also impacted on taking
      steroids. CONCLUSION: Decision-making was a complex process, involving evaluation
      of the personal costs and benefits of treatment; fear of side effects was the
      dominant concern. Compliance with treatment saves lives in this population.
      RELEVANCE TO CLINICAL PRACTICE: This study uncovers issues participants consider
      when making decisions regarding adherence and highlights the importance of the
      nurse's role in eliciting patients' concerns and the providing appropriate
      information to allay fears and misconceptions.

PMID- 17518871
TI  - The meaning of living with malodorous exuding ulcers.
AB  - AIM: This study illuminates the meaning of living with malodorous, exuding
      ulcers. BACKGROUND: Difficulties for patients with chronic ulcers and the ulcers'
      impact on patients' daily life are described in the literature. Suffering and
      consolation are also addressed in the literature as important issues in nursing
      care. DESIGN: The first author interviewed seven women and two men, aged 41-95,
      with various diagnoses. METHOD: We interpreted the transcribed interviews using a
      phenomenological hermeneutic method. RESULTS: Two processes were identified:
      'being struck down'- themes: feeling dirty, being trapped, losing confidence,
      losing hope, becoming frustrated and protecting oneself; and 'finding
      consolation'- themes: experiencing kinship, encountering genuineness and gaining
      control. The meaning of living with malodorous and exuding ulcers can be
      understood as being trapped in a debilitating process that slowly strikes one
      down. There is a longing for purity and wholeness and for one's life to improve.
      When people with malodorous, exuding ulcers encounter genuineness and feel loved,
      regarded and respected as fully human despite their ulcers, they feel purified.
      The contaminated body no longer contaminates their self-image and self-esteem and
      they feel restored and fully human again. Only when they feel fully human can
      they regain control and see life beyond their ulcers. CONCLUSION: Although nurses
      cannot make ulcers or smell disappear, they can contribute significantly to
      improve the patients' life. Finding consolation makes patients feel purified
      despite their contaminated body. RELEVANCE TO CLINICAL PRACTICE: This study
      points to the importance of seeing the human being beyond the ulcer and
      considering not only the body but the whole person.

PMID- 17518872
TI  - Experiences of loss and chronic sorrow in persons with severe chronic illness.
AB  - AIMS AND OBJECTIVES: The aims of the present study were to describe losses
      narrated by persons afflicted with severe chronic physical illness and to
      identify the concomitant occurrence of chronic sorrow. BACKGROUND: Reactions
      connected with repeated losses are referred to in the literature as chronic
      sorrow, which has recently been described in conjunction with chronic illness.
      DESIGN: A qualitative study with an abductive approach of analysis, including
      both inductive and deductive interpretations. METHOD: The study is based on 30
      persons of working age with average disease duration of 18 years. The average age
      was 51 years. All of the persons had personal assistance for at least three
      months because of considerable need for help in daily life due to physical
      disability. Each person was interviewed twice. There was also an independent
      assessment of the deductive results concerning chronic sorrow. RESULTS: The
      inductive findings show that all persons had experienced repeated physical,
      emotional and social losses. Most common were 'Loss of bodily function', 'Loss of
      relationship', 'Loss of autonomous life' and 'Loss of the life imagined'. 'Loss
      of identity' included the loss of human worth, dignity and a changed self-image.
      In addition, the deductive findings suggest that chronic sorrow exists in the
      study population. Sixteen of 30 participating subjects were assessed by both
      assessors to be in a state of chronic sorrow and there was an especially high
      agreement with respect to one criterion of chronic sorrow 'Loss experience,
      ongoing or single event' (28 of 30 subjects). CONCLUSIONS: This study shows that
      persons with severe chronic illness often experience recurring losses. These
      experiences are consistent with the phenomenon of chronic sorrow. RELEVANCE TO
      CLINICAL PRACTICE: Knowledge of the existence of chronic sorrow in persons with
      chronic illness will enable nurses to support these persons in a more sensitive
      and appropriate way.

PMID- 17518873
TI  - Self-evaluation and peer review--an example of action research in promoting self
      determination of patients with rheumatoid arthritis.
AB  - AIMS AND OBJECTIVES: The aim of this paper was to describe the areas that have
      been performed well and the areas in need of further development of rheumatoid
      arthritis patients. BACKGROUND: Nurses' self-evaluation and peer review are
      important methods for ascertaining the changes and success in the development of
      nursing practice. To date, there has been minimal research regarding the use of
      those evaluation methods in nursing practice. DESIGN: The findings of self
      evaluation and peer review of nurses are described in a participatory action
      research study aimed at promotion of self-determination for patients with
      rheumatoid arthritis. METHODS: In self-evaluation, the collection of data was
      accomplished using a self-evaluation instrument with the permanent nursing staff
      (n = 18), then analysed through quantitative methods. For peer review, the data
      were gathered through focus groups (n = 21) using a tool similar to the one used
      for self-evaluation. The participants included many of the same nurses as in self
      evaluation. The data were analysed using qualitative content analysis. RESULTS:
      Well-performed areas in nursing of rheumatoid arthritis patients were found to be
      promoting patient participation, supporting self-determination, performing
      patient-centred nursing and raising patient self-respect. The areas in need of
      development were connected to the nursing staff themselves: increasing
      collaboration of nursing staff, decreasing authoritarianism in nursing care and
      developing nursing practice with colleagues. CONCLUSIONS: Self-evaluation and
      peer review are complementary and support one another, especially since nurses
      were found to be more critical in their self-evaluations than in peer review.
      RELEVANCE TO CLINICAL PRACTICE: Both evaluation tools proved to be useful methods
      in the evaluation phase of the action research process as a means of professional
      development. Also assisting in the development of clinical nursing practice.

PMID- 17518874
TI  - Exploring determinants for quality of life among older people in pain and in need
      of help for daily living.
AB  - AIMS AND OBJECTIVES: The aim of the study was to investigate the quality of life
      and related factors among older people who are in pain and in need of help to
      manage daily living. BACKGROUND: To intervene against the low quality of life in
      nursing care knowledge about factors affecting it is needed and this is
      especially important for vulnerable people such as those who suffer from pain and
      who are in need of help to manage daily living. METHODS: Five hundred and twenty
      six people, aged 75-102 years participated in this study. RESULTS: Those in pain
      reported a significantly higher degree of all complaints and lower quality of
      life in all measures compared with those not in pain. Overall quality of life was
      associated with mobility problems, sleeping problems and depressed mood, while
      health-related quality of life was associated with living in special
      accommodations, walking problems, mobility problems and fatigue. CONCLUSIONS:
      Those in need of help to manage daily living and in pain seem to be at higher
      risk of lowered quality of life than those not in pain and the lower quality of
      life among those in pain is probably caused by the complex of complaints rather
      than pain per se. RELEVANCE TO CLINICAL PRACTICE: Daily nursing care should
      identify and treat the complex of complaints related to pain as well as pain
      itself, to improve everyday life and quality of life for older people in pain.

PMID- 17518875
TI  - Models for developing young nurse researchers: a discussion.

PMID- 17518876
TI  - Literature review: considerations in undertaking focus group research with
      culturally and linguistically diverse groups.
AB  - AIMS: This integrated literature review seeks to identify the key considerations
      in conducting focus groups and discusses the specific considerations for focus
      group research with culturally and linguistically diverse groups. BACKGROUND: The
      focus group method is a technique of group interview that generates data through
      the opinions expressed by participants. Focus groups have become an increasingly
      popular method of data collection in health care research. Although focus groups
      have been used extensively with Western populations, they are a particularly
      useful tool for engaging culturally and linguistically diverse populations. The
      success of focus groups in this context is dependent upon the cultural competence
      of the research team and the research questions. METHODS: The electronic
      databases Medline, CINAHL, Embase, Psychlit and the Internet using the Google
      Scholar search engine were explored using the search terms 'focus group',
      'cultural sensitivity', 'transcultural nursing', 'transcultural care', 'cultural
      diversity' and 'ethnic groups'. Hand searching of reference lists and relevant
      journals was also undertaken. English language articles were selected for the
      review if they discussed the following issues: (i) methodological implications of
      the focus group method; (ii) strengths and limitations of the focus group method;
      (iii) recommendations for researchers and (iv) use of the focus group in
      culturally and linguistically diverse groups. Conclusions were drawn from each of
      the articles and consensus regarding a summary of recommendations was derived
      from a minimum of two authors. RESULTS: Findings from this review revealed
      several key issues involving focus group implementation including recruitment,
      sample size, data collection, data analysis and use within multicultural
      populations. Strengths and limitations of the focus group method were also
      identified. CONCLUSIONS: Focus groups are a useful tool to expand existing
      knowledge about service provision and identify consumer needs that will assist in
      the development of future intervention programmes, particularly within
      multicultural populations. Careful planning related to methodological and
      pragmatic issues are critical in deriving effective data and protecting
      participants. RELEVANCE TO CLINICAL PRACTICE: Focus groups can facilitate
      increased understanding of perspectives of culturally and linguistically diverse
      groups and thereby shape clinical practice to better meet the needs of these
      groups.

PMID- 17518877
TI  - Nurses' knowledge of pain.
AB  - AIM: The aim of this study was to establish if postregistration education and
      clinical experience influence nurses' knowledge of pain. BACKGROUND: Inadequacies
      in the pain management process may not be tied to myth and bias originating from
      general attitudes and beliefs, but reflect inadequate pain knowledge. Design. A
      pain knowledge survey of 20 true/false statements was used to measure the
      knowledge base of two groups of nurses. This was incorporated in a self
      administered questionnaire that also addressed lifestyle factors of patients in
      pain, inferences of physical pain, general attitudes and beliefs about pain
      management. METHOD: One hundred questionnaires were distributed; 86 nurses
      returned the questionnaire giving a response rate of 86%. Following selection of
      the sample, 72 nurses participated in the study: 35 hospice/oncology nurses
      (specialist) and 37 district nurses (general). Data were analysed using SPSS.
      RESULTS: The specialist nurses had a more comprehensive knowledge base than the
      general nurses; however, their knowledge scores did not appear to be related to
      their experience in terms of years within the nursing profession. CONCLUSION:
      Whilst educational programmes contribute to an increase in knowledge, it would
      appear that the working environment has an influence on the development and use
      of this knowledge. It is suggested that the clinical environment in which the
      specialist nurse works can induce feelings of reduced self-efficacy and low
      personal control. To ease tension, strategies are used that can result in nurses
      refusing to endorse their knowledge, which can increase patients' pain. RELEVANCE
      TO CLINICAL PRACTICE: Clinical supervision will serve to increase the nurses'
      self-awareness; however, without power and autonomy to make decisions and affect
      change, feelings of helplessness, reduced self-efficacy and cognitive dissonance
      can increase. This may explain why, despite educational efforts to increase
      knowledge, a concomitant change in practice has not occurred.

PMID- 17518878
TI  - Nurses' experience with the clinical application of a research-based nursing
      protocol in a long-term care setting.
AB  - AIM: To describe nurses' experience with the clinical application of a research
      based nursing protocol (The Serial Trial Intervention) within a long-term care
      setting. DESIGN: A descriptive, qualitative study was conducted with a
      convenience sample of eight nurses from three nursing homes, who assessed and
      treated residents with dementia according to the Serial Trial Intervention
      protocol. METHODS: Each nurse participated in a semi-structured interview between
      September 2003 and May 2004. Interviews were audiotaped and transcribed verbatim.
      Qualitative content analysis of the data, including thematic analysis, was used
      to identify patterns of experience. RESULTS: Three themes emerged that offer
      insight into the factors contributing to implementation of research-based
      practice in a clinical setting. These include determining to intervene, pertinent
      steps of the protocol and facilitators and barriers. CONCLUSIONS: The interplay
      between the protocol, the residents receiving care, the nurses providing care and
      the setting in which the care is provided, are interacting to affect the outcomes
      expected. RELEVANCE TO CLINICAL PRACTICE: Nurses who recognize the research
      process, the need for continual improvement in patient care and who possess
      competency in comprehensive physical assessment are needed to implement this
      evidence-based protocol successfully. The regulatory atmosphere, workload
      structure and interdisciplinary collaboration are additional factors contributing
      to the successful use of the Serial Trial Intervention.

PMID- 17518879
TI  - An analysis of the experiences of clinical supervision on Registered Nurses
      undertaking MSc/graduate diploma in renal and urological nursing and on their
      clinical supervisors.
AB  - AIMS: The aim of this study was to elicit clinical supervisors' and supervisees'
      experiences of clinical supervision while undertaking MSc/Graduate Diploma
      Programme in Renal and Urological Nursing. BACKGROUND: Formal systems of clinical
      supervision have not been implemented in the Republic of Ireland. There is a
      growing awareness of their effectiveness in enhancing analytic skills and in
      helping to retain staff in clinical practice. Clinical supervision was
      incorporated in the MSc/Graduate Diploma Programme to enhance professional growth
      and development for students. DESIGN: A qualitative descriptive research design
      was used in this study. METHODS: A purposive sample of 10 Registered Nurses
      participated in the study; five were clinical supervisors and the other five were
      supervisees. The study was undertaken at a large teaching hospital in the
      Republic of Ireland. Data were collected by semi-structured interviews and
      analysed using content analysis. RESULTS: Following data analysis, six major
      categories emerged. These were, 'positive aspects''negative aspects', 'factors,
      which had an impact on the process of clinical supervision', 'support', 'formal
      systems of clinical supervision', 'reflective practice in groups'. CONCLUSIONS:
      There was a general feeling that clinical supervision was a good experience for
      many members of this study group. The concept of clinical supervision was
      perceived as an inappropriate term to encompass the complexity of the clinical
      supervision sessions. This begs the question: is clinical supervision a practice
      with no name or should it be called something else? Giving a practice an
      appropriate name may empower registered nurses to implement this practice with
      confidence. RELEVANCE TO CLINICAL PRACTICE: The findings of this study have
      implications for management and for the clinical environment, in terms of
      supporting and preparing practitioners to develop their critical and analytic
      skills.

PMID- 17518880
TI  - Nurses' perceptions, understanding and experiences of health promotion.
AB  - AIM: This paper presents an account of nurses' perceptions and understanding of
      health promotion in an acute setting. BACKGROUND: Health promotion is considered
      the remit of every nurse. To engage in health-promoting practice, however, nurses
      need to understand the term 'health promotion' clearly. METHOD: A single
      qualitative embedded case study was used. Purposive sampling of eight nurses was
      employed. Initially, theses nurses were observed in practice and, following this,
      a semi-structured one-to-one interview was conducted with each observed nurse.
      Qualitative data analysis guided by work of Miles and Huberman was employed.
      RESULTS: The data revealed one main theme: health-promoting nursing practice and
      this consisted of six categories and five subcategories. The findings indicated
      that nurses struggled to describe their understanding of health promotion, their
      understanding was limited and the strategies described to conduct health
      promotion were narrow and focused on the individual. Their perceptions and
      descriptions of health promotion were more in keeping with the traditional health
      education approach. Overall health promotion was reported to occur infrequently,
      being added on if the nurse had time. Factors relating to education,
      organizational and management issues were identified as key barriers prohibiting
      health-promoting nursing practice. CONCLUSIONS: Nurses must recognize that health
      promotion is a broad concept that does not exclusively focus on the individual or
      lifestyle factors. Nurses must be educated to recognize health-promoting
      opportunities in the acute setting, as well as how to plan for and conduct health
      promotion so that it becomes integral to practice. A review of the methods of
      organizing and delivering nursing care is also advocated. RELEVANCE TO CLINICAL
      PRACTICE: Ward managers have an important role in supporting nurses, creating a
      culture for health promotion and sharing power in decision-making processes, so
      that nurses feel valued and empowered.

PMID- 17518881
TI  - Nurse practitioner-client interaction as resource exchange: the nurse's view (NP
      client interaction).
AB  - AIM: The aim of this study was to explore nurse practitioner (NP) client
      encounters from the nurse's perspective using a resource exchange paradigm.
      BACKGROUND: In health care interactions there is a need to examine what is
      reinforcing from the nurse's perspective. DESIGN: An exploratory descriptive
      design was used to address the following research questions: Prior to a clinic
      visit with midlife female clients what are NPs expectations of resources
      provided? What resources are actually provided during the visit with the NP and
      the client? To what extent is there congruence between the NP's expectations and
      the resources actually provided during a clinic visit? METHODS: The participants
      included two expert NPs and eight midlife female clients. Data for the study were
      derived from an initial larger study which examined resource exchange from the
      client angle and consisted of audio-taped pre- and postencounter interviews with
      the NPs, audiotapes of the entire clinic visit and field notes recorded by the
      researcher of the client visits. Content analysis was conducted using ETHNOGRPAH
      software. RESULTS: NPs anticipated that a broad range of resources would be
      provided. The most prominent resources provided across visits were information,
      services, time and affirmation (that included affirmation itself, reassurance,
      reinforcement of positive health behaviours, support and feedback). In the more
      established relationships nurse self-disclosure was evident. CONCLUSIONS:
      Resource exchange theoretical formulations can be applied to NP-client
      interactions to understand and explain the specific nature of resources NPs
      expect to provide and actually provide. RELEVANCE TO CLINICAL PRACTICE: The
      nature of resources NPs provide, relationship development, types of exchange
      relationships in clinical practice were identified and posit a beginning typology
      for NPs to apply in their own clinical practice.

PMID- 17518882
TI  - Initiation, choice and satisfaction of nursing appointments in general practice:
      a cross-sectional survey of patients and nurses.
AB  - AIMS AND OBJECTIVES: To compare patients' and nurses' perceptions regarding the
      initiation of appointments, and to assess patients' satisfaction with appointment
      provision. BACKGROUND: Appointment provision is changing in primary care and no
      research has assessed the initiation of nursing appointments. DESIGN: Cross
      sectional survey assessing patients' and nurses' perceptions of the same
      appointment. METHODS: A survey distributed to a convenience sample of patients
      attending nursing appointments for a two-week period. RESULTS: Patients are
      highly satisfied with appointment provision. There is little agreement between
      patients and nursing staff regarding the initiation of an appointment.
      CONCLUSION: Patients are satisfied with appointment provision which can
      accommodate different perceptions regarding the initiation of an appointment.
      RELEVANCE TO CLINICAL PRACTICE: It is important to acknowledge patients'
      perceptions regarding appointment management as the views of nursing staff differ
      regarding the initiation of the appointment.

PMID- 17518883
TI  - A nurse short message service by cellular phone in type-2 diabetic patients for
      six months.
AB  - AIM: To investigate the effectiveness of a nurse short message service (SMS) by
      cellular phone and wire Internet on plasma glucose levels in people with diabetes
      for six months. BACKGROUND: Blood glucose management system using telemedicine
      approaches may maintain the appropriate blood glucose levels in type-2 diabetic
      patients. DESIGN: A control group pre-test-post-test design was used to assess
      the effectiveness of nurse's education. METHODS: Twenty-five patients were
      randomly assigned to an intervention group and 26 to a control group. The
      intervention was applied for six months. The goal of the intervention was to keep
      blood glucose concentrations close to the normal range. Participants were
      requested to input their blood glucose level, diet and exercise diary everyday in
      the website by cellular phone or wire Internet. The researcher sends optimal
      recommendations to each patient using SMS by cellular phone and wire Internet
      weekly. RESULTS: Glycosylated hemoglobin (HbA(1)c) decreased 1.15% points at
      three months and 1.05% points at six months compared with baseline in the
      intervention group. Patients in the intervention group had a decrease of two
      hours post meal glucose (2HPMG) of 85.1 mg/dl at three months and 63.1 mg/dl at
      six months compared with baseline. CONCLUSION: This web-based intervention using
      SMS of cellular phone improved HbA(1)c and 2HPMG for six months in type-2
      diabetic patients. RELEVANCE TO CLINICAL PRACTICE: An SMS of cellular phone
      intervention by a nurse can reduce HbA(1)c and 2HPMG for six months in type-2
      diabetic patients.

PMID- 17518884
TI  - Development and validation of a learning needs assessment scale: a continuing
      professional education tool for multiple sclerosis specialist nurses.
AB  - AIM: To develop and validate a learning needs assessment scale. BACKGROUND:
      Learning needs analysis is a central component of continuing professional
      development but there is a lack of psychometrically developed learning needs
      assessment tools. Self-assessment questionnaires are emerging as a key method.
      The development of a learning needs analysis scale for multiple sclerosis
      specialist nurses is described. DESIGN: A psychometric approach comprising the
      three phases of the development and testing of the scale are outlined. METHOD:
      Phase 1: Item identification using a literature review; postal survey of
      stakeholders (n = 320), 20 nurse interviews; four nurse focus groups; five
      telephone interviews with people with MS. Phase 2: Refinement of draft scale and
      establishing face and content validity testing using an expert panel. Phase 3:
      Testing of draft scale using data from a postal survey (n = 47 MS specialist
      nurses) to assess the feasibility and effectiveness of scale, internal
      consistency and construct validity. Test-retest reliability was assessed using
      data from 17 MS specialist nurse respondents to calculate intra-class correlation
      coefficients. RESULTS: The data from the different study phases informed scale
      refinement. The validity and reliability of the scale was confirmed through
      testing. CONCLUSION: The study provides an example of how a robust learning needs
      assessment scale may be developed for a specialist area of nursing practice to be
      used in conjunction with more subjective approaches. RELEVANCE TO CLINICAL
      PRACTICE: High quality nursing care depends upon a competent nursing workforce
      that engages in continuing professional development. This study provides an
      example of a psychometrically developed learning needs assessment scale to inform
      continuing professional development needs of nurses working in a specialist area
      of practice.

PMID- 17518885
TI  - Contemporary day surgery: patients' experience of discharge and recovery.
AB  - AIM: To explore and reveal patients' perceptions of discharge arrangements and
      recovery following day surgery. INTRODUCTION: Contemporary day surgery is
      increasingly being used to carry out elective surgical procedures enabling
      patients to be discharged on the same day. The Department of Health and
      government modernization programmes in the UK have encouraged this rapid growth.
      Preparation for discharge is important because patients require knowledge and
      understanding about self-management and access to primary health care services if
      required. METHODS: Using a phenomenological approach, data were collected by
      unstructured interviews from 30 patients undergoing gynaecology, urology and
      general surgery procedures. RESULTS: Deficits in patient preparation for
      discharge including the timing of information giving postprocedure for all groups
      were highlighted. The gynaecology patients pointed to a specific lack of verbal
      information about resuming sexual activity following procedures. Some general
      surgery and urology patients alluded to finding it stressful coping with threats
      to body image through 'skin discoloration', 'swelling' or 'bruising', because
      they did not know what to do. A number of urology patients talked about the
      challenges posed by difficulty with voiding, dysuria and haematuria. RELEVANCE TO
      CLINICAL PRACTICE: The results and problems identified have applicability for the
      development of discharge planning services and patient education in a day surgery
      context. It is suggested that the use of evidenced-based and innovative
      interventions among health professionals might improve patient outcomes.

PMID- 17518886
TI  - Patients' experiences at home after day case cystoscopy.
AB  - AIM: To determine patients' problems with day case cystoscopy and their problem
      solving ways and patients' self-care at home. BACKGROUND: Day surgery has become
      increasingly common in the last 20 years. Cystoscopic procedures are increasingly
      being carried out as a diagnostic and therapeutic procedures. DESIGN AND METHOD:
      This descriptive/prospective study comprised 50 patients undergoing day case
      cystoscopic procedures in the university hospital of Turkey. The data were
      collected using telephone interview three days after the procedure. The two
      questionnaire used were Symptom Measurement Questionnaire and Symptom Management
      Questionnaire. Discharge information and written instruction was given to all
      patients. RESULTS: It was found in the investigation that the most common
      problems experienced by the patients were tiredness, haematuria, dysuria, pain
      over bladder and difficulty in voiding after flexible cystoscopy in first day.
      Generally, urinary elimination problems were experienced by majority of the
      patients. At second day, these problems were also common. The mean score for all
      problems decreased after three days. The patients stated that they were able to
      deal with their symptoms either independently or to a lesser extent with
      assistance of a carer. But they were unable to deal with problems such as
      especially haematuria. CONCLUSION: Problems experiences by the patients at home
      after cystoscopy influenced some daily living activities. The problems related to
      voiding are more frequently observed after cystoscopy. Although some these
      problems are related to the procedures, some were present previously. RELEVANCE
      TO CLINICAL PRACTICE: This findings indicate that patient-centred care should be
      strengthened at home in urological day surgery.

PMID- 17518888
TI  - Making patients better: a qualitative descriptive study of registered nurses'
      reasons for working in surgical areas.
AB  - AIMS: To explore the reasons and motivation identified by qualified nurses for
      working within the surgical area. BACKGROUND: Little is known about the career
      decisions qualified nurses make, although it is clear that some areas of practice
      are more popular than others. This qualitative descriptive study considers one
      common area, surgery, and explores the motivation for decisions made by
      Registered Nurses (RNs) to work in this area. METHOD: A sample of 16 RNs working
      within surgical areas participated in semi-structured interviews, using a
      thematic interview schedule. Findings were analysed using the framework suggested
      by Morse and Field. RESULTS: Analysis of findings indicates that all participants
      actively chose to work within surgery and that this was because of the pace and
      turnover of surgical work, personal satisfaction at the recovery of patients; the
      close links between this type of work; and participants' original aims when first
      entering nursing and participants' preference of surgery to other areas of
      nursing work. Participants actively rejected working in areas where patients were
      likely to suffer from chronic long-term conditions where recovery was unlikely
      and felt that these areas were likely to be depressing and unrewarding.
      CONCLUSION: These findings suggest that participants actively chose to work with
      'healthy' patients in preference to those who may be considered 'ill', and this
      is closely linked to the identified need of participants to be able to 'make
      patients better'. Participants were reluctant to work in areas where they would
      be unlikely to achieve this aim. RELEVANCE TO CLINICAL PRACTICE: The reluctance
      of surgical nurses to work with patients who were considered 'ill', in preference
      to 'healthy' patients must be acknowledged. Findings reflect different
      professional perspectives on the purpose of nursing work and suggest that
      qualified staff choose their clinical specialism based on their own personal
      sense of professional purpose, with consequent implications for both the
      recruitment and retention of qualified staff.

PMID- 17518887
TI  - Nurses' knowledge and skills in colonoscopy patients' pain management.
AB  - AIM: This study aimed to describe the knowledge and skills of nurses in managing
      pain during colonoscopy procedures. BACKGROUND: Colonoscopy is a procedure to
      diagnose diseases of the intestine, and patients consider it even painful.
      However, few studies have described patients' pain management during the
      colonoscopy procedure. DESIGN: A quantitative survey design was used. The data
      were collected from colonoscopy nurses with a self-completed semi-structured
      questionnaire developed for the study. METHODS: The hospitals performing
      colonoscopies in Finland, with the exception of the ones where the questionnaire
      was pilot-tested, were included in the study (n = 12). The optional sample was
      drawn by mailing questionnaires (n = 147) to endoscopy units to be filled in by
      three colonoscopy nurses during 2002. The response rate was 79% (n = 116).
      RESULTS: The majority of nurses used versatile non-pharmacological methods of
      managing pain and had practice-based knowledge of pain management during the
      colonoscopy procedure, but pain education and the acquisition of new professional
      knowledge were rarely reported. Pain scales were not in use and ethical
      conversation was lacking among the endoscopy staff in most (95%) hospitals.
      CONCLUSION: The study showed that colonoscopy nurses used numerous non
      pharmacological methods, but only rarely acquired professional knowledge. There
      was a lack of pain scales and ethical conversation in the participating endoscopy
      units. RELEVANCE TO CLINICAL PRACTICE: The results can be used to improve the
      treatment of pain during colonoscopy procedures and endoscopy nurses' education.
      Nurses should be motivated by education and ethical conversation. Future studies
      should aim to analyse patients' own evaluation of pain during the colonoscopy
      procedure. The applicability of the existing pain scales and non-pharmacological
      methods should be tested in practice.

PMID- 17518889
TI  - The comparison of effectiveness of two modalities of mental health nurse follow
      up programmes for female outpatients with depression in Taipei, Taiwan.
AB  - AIMS AND OBJECTIVES: This study compares the effectiveness of two modalities of
      mental health nurse three-month follow-up programmes: telephone counselling
      programme and group therapy programme for female outpatients with depression.
      BACKGROUND: The lifetime prevalence of major depression is 15% and is about twice
      as common in women as in men. Outpatients with depression often discontinue their
      treatment after the initial visits to their physicians. METHODS: This study used
      a quasi-experimental, pre-post-test comparison group design. Twenty-six female
      outpatients with depression were assigned to one of follow-up programmes:
      telephone counselling programme or group therapy programme. To qualify for group
      therapy programme, potential participants were required to come to group sessions
      weekly. To be accepted into telephone counselling programme, potential
      participants had to be able to be contacted by phone regularly. Mental health
      nurse three-month follow-up programmes included care management and structured
      psychotherapy. Patients in telephone counselling programme received 10 regular
      telephone calls of 30-60 minutes each. Patients in group therapy programme
      received 12 sessions of weekly group meetings of 90-120 minutes each. RESULTS:
      Wilcoxon signed ranks tests provided evidence that the group therapy programme (S
      = -52.5, p < 0.001; S = 31.5, p = 0.046) and telephone counselling programme (S =
      -36, p = 0.002; S = 25, p = 0.050) follow-up programmes were effective in terms
      of relieving depressed symptoms and improving quality of life. According to
      Quade's analysis of covariance, telephone counselling programme and group therapy
      programme appeared to have similar effects of relieving depressed symptoms
      (F(1,24) = 0.06, p = 0.813) and increasing quality of life (F(1,24) = 0.07, p =
      0.792). While there was no significant difference in using emergency services (
      chi(2)(1)= 0.89, p = 0.539) between telephone counselling programme and group
      therapy programme, the rate of adherence to scheduled outpatient appointments
      with psychiatrists was higher among patients in group therapy programme than
      patients in telephone counselling programme (chi(2)(3) = 8.67, p = 0.034).
      CONCLUSIONS: Establishing two modalities of mental health nurse follow-up
      programmes in Taiwan could benefit patients with different needs. RELEVANCE TO
      CLINICAL PRACTICE: Mental health nurses specialized in management of depression
      could provide not only care management but also structured psychotherapy.

PMID- 17518890
TI  - The perceived burden among Chinese family caregivers of people with
      schizophrenia.
AB  - AIMS: The aim of this study was to examine the level of perceived burden of the
      Chinese families caring for a relative with schizophrenia and to test its
      associations with their demographic characteristics, social and family factors
      and health condition. BACKGROUND: Despite the increased demands on family members
      to provide care for patients with schizophrenia in community care, little is
      known about the level of family burden among these family caregivers and its
      relationship with their demographic, social and cultural backgrounds. METHODS:
      This was a cross-sectional descriptive study. A total of 203 family caregivers
      were recruited from three regional psychiatric outpatient clinics in Hong Kong.
      They were asked to complete a set of well-validated questionnaires, consisting of
      the Chinese version of four instruments - Family Burden Interview Schedule,
      Family Assessment Device, Six-item Social Support Questionnaire and MOS 36-Item
      Short Form Health Survey and a socio-demographic data sheet. Statistical analyses
      were conducted to test the differences in mean burden scores between subgroups,
      the inter-relationships among the mean scores of the scales and socio-demographic
      variables and the predictors of family burden. RESULTS: The families who
      perceived a higher level of caregiver burden were those who lived in a family
      with poorer functioning, worse health status and less satisfaction of social
      support. The caregivers' burden score was positively correlated with their age;
      conversely, it was negatively correlated with their monthly household income and
      number of family members living with patient. Social support was the best
      predictor of caregiver burden. CONCLUSION: These findings increase our
      understanding about the socio-demographic and cultural variables influencing the
      well being of family caregivers of a relative with schizophrenia. Helping
      families to maintain and enhance a supportive social network may represent a
      useful means to reduce family burden in schizophrenia. RELEVANCE TO CLINICAL
      PRACTICE: This understanding helps health professionals and researchers to
      identify different sources and domains of burden from a Chinese cultural
      perspective and take into account of these factors when planning interventions
      for family caregivers.

PMID- 17518891
TI  - Health literacy and the information needs and dilemmas of first-time mothers over
      35 years.
AB  - AIM AND OBJECTIVES: This paper aims to highlight the information-based dilemmas
      of a particular group of healthcare patients, first-time mothers over 35 years.
      BACKGROUND: In recent years, there has been a proliferation of health-related
      information and a move towards greater public access to health information as an
      important step towards patient education and empowerment. Information
      technologies, such as the Internet, have added considerable momentum to this
      trend. Many health professionals now consider the provision of detailed health
      information to patients as requisite for informed decision making. Within the
      literature there is some emphasis on the importance of patient understanding of
      information received; however, to date, few studies have considered information
      over-consumption as problematic. METHODS: Using in-depth interviews, a sample of
      22 first-time mothers over 35 years was interviewed over three junctures: 35
      weeks gestation, 10-14 days postpartum and six to eight months postpartum. Three
      focus group interviews of midwives and maternal and child health nurses were also
      conducted. This paper was undertaken as part of a larger project to evaluate the
      experience of first mothering over 35 years. RESULTS: Mothers in this study were
      found to have access to large volumes of health information. This tendency was
      driven by both the women and the health professionals who cared for them.
      Midwives and maternal and child health nurses revealed a tendency to provide
      older first-time mothers with considerable health information of a medical
      orientation, understanding that this is what the women required. However, despite
      common perceptions of empowerment, the consumption of medical-type information
      proved frightening and many mothers described feeling overwhelmed by 'knowing too
      much'. CONCLUSION: This study contributes to the limited understanding of the
      information needs of a growing group of childbearing women, first-time mothers
      over 35 years. By providing an insight into the 'downside' of extensive health
      information, nursing staff, in particular, may consider the amount and type of
      information they distribute. Some suggestions are offered to health professionals
      to ameliorate the information-based dilemmas of these women. RELEVANCE TO
      CLINICAL PRACTICE: As the number of childbearing women over 35 years continues to
      grow, it is important for health professionals to understand the particular needs
      of this group. In doing so, doctors, midwives and maternal and child health
      nurses may be in a position to provide more meaningful maternal support.

PMID- 17518892
TI  - Effectiveness of hand-washing teaching programs for families of children in
      paediatric intensive care units.
AB  - AIMS: The authors developed a video-centred teaching program based on social
      learning principles to demonstrate hand-washing technique. A comparison was made
      between families who viewed the video and families who were taught the same
      techniques with the aid of an illustrated poster in terms of compliance and
      improvement in hand-washing skills. BACKGROUND: Nosocomial infections are a
      significant cause of morbidity and mortality in paediatric intensive care unit
      patients. Hand hygiene is considered the most important preventive action against
      hospital-acquired infections. A number of studies have shown that increased
      compliance with hand-washing guidelines for health-care workers leads to
      decreases in nosocomial infection rates. Furthermore, recommendations have been
      made to ensure that parents who visit their children in intensive care units wash
      their hands first. STUDY DESIGN: Quasi-experimental time series. Compliance and
      accuracy measurements were collected during one to five visits following the
      initial teaching intervention. METHODS: A total of 123 families, who visited
      paediatric intensive care units, were recruited and assigned to two groups - one
      experimental (61 families) and the other a comparison group (62). Participants in
      the comparison group were taught hand-washing skills using simple illustrations.
      A 20-item hand-washing checklist was used to examine hand-washing compliance and
      accuracy. RESULTS: No significant differences were noted in terms of demographics
      between the two groups. Results from a general estimated equation analysis showed
      that families in the experimental group had higher compliance and accuracy scores
      at statistically significant levels. CONCLUSION: The video-based teaching program
      was effective in increasing compliance and accuracy with a hand-washing policy
      among families with children in intensive care units. RELEVANCE TO CLINICAL
      PRACTICE: The education program is a simple, low-cost, low technology
      intervention for substantially reducing the incidence of nosocomial infection.

PMID- 17518893
TI  - The maternal self in pregnant women undergoing maternal serum screening.
AB  - BACKGROUND: Much has been written about the anxiety of pregnant women undergoing
      maternal serum screening, but little has focused on the maternal self. AIMS: The
      purpose of this study was to explore how the maternal self was affected by
      abnormal results of prenatal screening. Design. A qualitative design was used,
      based upon a grounded theory method. METHODS: Twenty-seven women undergoing
      maternal serum screening engaged in qualitative interviews about how abnormal
      results affected them and their family life. RESULTS: This study identified three
      forms of maternal self in women who had been informed of abnormal results of
      maternal serum screening. The three forms of maternal self could be described as
      self-stigmatizing, self-conflicting and self-knowledgeable. CONCLUSION: The self
      stigmatizing and self-conflicting resulted from painful body image. The pregnant
      women responded to this vulnerability by reflecting on their experiences and
      constituting self-knowledgeable. RELEVANCE TO CLINICAL PRACTICE: This study
      demonstrated that ethical issues were implicit in prenatal counselling in terms
      of various forms of maternal self. Understanding the self-perceptions of pregnant
      women coping with an increased risk of Down Syndrome could be very significant in
      delivering prenatal genetic counselling.

PMID- 17518894
TI  - Healthcare workers and influenza vaccination. Commentary on Canning HS, Phillips
      J & Allsup S (2005). Healthcare workers beliefs about influenza vaccine and the
      reasons for non-vaccination - a cross-sectional survey. Journal of Clinical
      Nursing 14, 922-925.

PMID- 17518895
TI  - Commentary on Grandell-Niemi H, Hupli M, Leino-Kilpi H & Puuka P (2005). Finnish
      nurses and nursing students' pharmacological skills. Journal of Clinical
      Nursing14, 685-694.

PMID- 17518896
TI  - Commentary on Liu JE, Mok E & Wong T (2006). Caring in nursing: investigating the
      meaning of caring from the perspective of cancer patients in Beijing, China.
      Journal of Clinical Nursing, 15, 188-196.

PMID- 17518898
TI  - The new direction in dental continuing education.

PMID- 17518899
TI  - Adhesives and foundations.

PMID- 17518900
TI  - Interdisciplinary approach to treating a patient with amelogenesis imperfecta: a
      clinical report.
AB  - Treatment of a patient with amelogenesis imperfecta (AI) presents a real problem
      from both functional and esthetic points of view. An esthetic result also will
      result in an improvement in the patient's quality of life. This clinical report
      illustrates the oral rehabilitation of a 24-year-old man diagnosed with
      hypomature type of AI. The aim of treatment was to both restore esthetics and
      improve masticatory function. Esthetic expectations of the patient were
      successfully attained by placing all-porcelain crowns from canine to canine in
      each arch, 12 crowns total. Moreover, metal-ceramic three-unit fixed partial
      dentures for the missing mandibular right first molars were fabricated for the
      patient's masticatory function. Resin composite restorations were applied to the
      maxillary premolars, the maxillary right first molar, the mandibular left
      premolars, and the right first premolar to modify the occlusion. No deterioration
      in the restorations and no pathology associated with the rehabilitation were
      found at the 1-year recall, and the patient's esthetic and functional
      expectations were satisfied. CLINICAL SIGNIFICANCE This article provides an
      overview of an interdisciplinary approach to treating the difficult condition of
      AI using a combination of treatments to achieve optimal esthetics and function.

PMID- 17518902
TI  - Esthetic and functional rehabilitation of a patient with nonsyndromic
      oligodontia: a case report from China.
AB  - STATEMENT OF THE PROBLEM: Oligodontia (severe partial anodontia) is a
      developmental dental anomaly. It is either an isolated trait or part of a
      syndrome. Oligodontia is characterized by the congenital absence of more than six
      permanent teeth except the third molars. Treatment often calls for facilitated
      surgical techniques, but less severe cases can be treated conventionally in a
      normally equipped dental office. CASE PRESENTATION: A case of oligodontia treated
      with prosthetic rehabilitation is presented in this article to remind clinicians
      of the anomaly. A medical history was taken and clinical and radiographic
      examinations were made. It is emphasized that conventional prosthetic treatment
      can lead to a satisfactory result. The patient was treated with fully extending
      denture prostheses. An overdenture was designed in the maxillary arch, while a
      removable partial denture was made in the mandibular arch. RESULTS: The patient's
      speech and masticatory function improved greatly. He was also pleased with better
      facial esthetics. Observed temporomandibular joint dysfunction also ameliorated
      after the treatment. CONCLUSION: Dental clinicians should keep in mind that there
      are good possibilities with conventional prosthodontic techniques to help
      patients with dental anomalies. Treatment not only improves speech and
      masticatory function but also has psychological implications that may greatly
      help in regaining self-confidence. CLINICAL SIGNIFICANCE Patients suffering from
      oligodontia may have severe psychological, esthetic, and functional problems.
      Thus, early diagnosis and treatment of these patients are necessary.

PMID- 17518904
TI  - Effect of ZOE temporary restoration on resin-dentin bond strength using different
      adhesive strategies.
AB  - STATEMENT OF THE PROBLEM: Eugenol is a radical scavenger that inhibits the
      polymerization of resin materials. Little is known about the effect of a eugenol
      containing temporary restorative material on the resin-dentin bond strength of
      adhesive systems that partially dissolves and modifies the smear layer. PURPOSE
      OF THE STUDY: The aim of this study was to evaluate the effect of eugenol
      containing temporary restoration (zinc oxide eugenol [ZOE]) on the resin-dentin
      microshear bond strength of etch-and-rinse and self-etch adhesives. MATERIAL AND
      METHODS: The roots of 18 human molars were removed and the crowns of the teeth
      were transversally sectioned into two halves. The dentin surfaces were embedded
      in acrylic resin. Half of the samples were stored while the remaining specimens
      were restored with eugenol-containing temporary restoration. After 24 hours, the
      ZOE restoration was mechanically removed and dentin surfaces were ultrasonically
      cleaned. Dentin surfaces were treated with one of the following adhesives: Single
      Bond, Clearfil SE, and iBond. Six cylinders of Z250 (0.5 mm high and 0.75 mm in
      diameter) were applied to each bonded dentin surface using a tygon tube. After
      storage for 24 hours, the specimens were subjected to micro-shear testing. The
      data was subjected to a two-way analysis of variance and Tukey's test
      (alpha=0.05). RESULTS: Similar bond strength values were obtained for Single Bond
      (p=0.48) either in the control or in the ZOE-treated group. For both self-etch
      systems, the bond strength in the ZOE-treated group was statistically lower than
      the control group (p < 0.01). CONCLUSIONS: Although the prior use of eugenol
      containing temporary restoration (IRM) affects the resin-dentin bond strength of
      the etch-and-rinse Single Bond, a more pronounced reduction on bond strength was
      observed for the two self-etch systems evaluated (iBond, Clearfil SE Bond).
      CLINICAL SIGNIFICANCE Eugenol-containing provisional restorations (IRM) should
      not be used prior to the placement of resin restorations bonded with the two-step
      etch-and-rinse Single Bond and the self-etch adhesives systems iBond and Clearfil
      SE Bond.

PMID- 17518906
TI  - Evaluation of the relationship between subjects' perception and professional
      assessment of esthetic treatment needs.
AB  - PURPOSE: The purposes of the present study were to (1) evaluate the esthetic
      dental treatment need by means of two special questionnaires, (2) determine the
      reliability and the construct validity of the measurement scales derived from
      these questionnaires, and (3) investigate the relationship between Greek
      subjects' perception and a professional examiner's assessment regarding the
      esthetic treatment need. MATERIALS AND METHODS: Participants in this survey
      consisted of 132 subjects (48 males with mean age 39.0 +/- 14.5 years old, 84
      females with mean age 41.7 +/- 14.5 years old) with natural teeth and fixed
      restorations. Subjects were asked to complete a special self-evaluation
      questionnaire consisting of 12 items. During the next stage, all participants
      were clinically examined by an experienced examiner and the data collected were
      used to fill out a second special professional assessment questionnaire
      consisting of 20 items. The forms structure used were in accordance with well
      established indices used in orthodontics for assessing esthetic treatment need.
      RESULTS: The reliability of the multiple correspondence analysis (MCA) analysis
      derived scales was very satisfactory (Cronbach's a coefficient: a =0.82) for the
      total scale of the self-evaluation measurement. For the professional assessment
      scale, the reliability of the total scale was almost perfect (a=0.92). The MCA
      revealed one reliable factorial construct for the self-evaluation measurement
      scale and two reliable constructs for the professional measurement scale.
      Pearson's correlation coefficient indicated a very low agreement between self
      evaluation and professional measurement scales. CONCLUSION: The findings of this
      survey suggest that there was a relative disagreement between subjects'
      perception and professional assessment regarding the need for esthetic dental
      treatment. CLINICAL SIGNIFICANCE In the present survey, the agreement between
      subjects' perception and clinical assessment of esthetic dental treatment need
      was found to be very low, which highlighted the discrepancies between patients'
      and dentists' perceptions of esthetic needs.

PMID- 17518908
TI  - Attitudes and problems faced by both patients and dentists in esthetic dentistry
      today: an AAED membership survey.

PMID- 17518909
TI  - Critical appraisal. Class II composite resin restorations with gingival margins
      in dentin.

PMID- 17518910
TI  - Bleeding disorders and oral health.

PMID- 17518911
TI  - Effects of different substance misuse in genital reflexes of paradoxical sleep
      deprived male rats.
AB  - As psychostimulants are widely abused, their neurochemical and behavioral effects
      have been extensively studied for many years. Our previous data demonstrate that
      paradoxical sleep deprivation (PSD) enhances drug-induced penile erection and
      ejaculation. PSD in association to drugs of abuse like cocaine potentiated
      genital reflexes in male rats. In this sense, the present study investigated if
      three substances abused by young people--such as Delta(9)-tetrahydrocannabinol
      (Delta(9)THC), alcohol and caffeine--had any significant effect on the genital
      reflexes in PSD rats. The results indicated that PSD induced erection in 50% of
      the rats and 20% ejaculated. In addition, there was no significant alteration in
      the number of animals exhibiting genital reflexes neither on the frequency of
      these behaviors when challenged with Delta(9)-THC or alcohol or caffeine after 96
      h of PSD. These findings show that Delta(9)THC, alcohol and caffeine when
      administrated isolated did not produce alterations in genital reflexes in the PSD
      male rats.

PMID- 17518912
TI  - Automatic semantic priming in the left and right hemispheres.
AB  - We investigated hemispheric differences and inter-hemispheric transfer of
      facilitation in automatic semantic priming, using prime-target pairs composed of
      words of the same category but not associated (e.g. skirt-glove), and a blank
      target baseline condition. Reaction time and accuracy were measured at short (300
      ms) intervals between prime and target onsets, using a go/no-go task to
      discriminate between word or non-word targets. Reaction times were facilitated
      more for target words presented in the right visual field (RVF) compared to the
      left visual field (LVF), and targets presented in RVF were primed in both visual
      fields, whereas targets presented in LVF were primed by primes in the LVF only.
      These results suggest that both hemispheres are capable of automatic priming at
      very short stimulus onset asymmetries (SOA), but cross-hemisphere priming occurs
      only in the left hemisphere.

PMID- 17518913
TI  - Young children's representations of peers' distress: associations to children's
      social functioning and acceptance of distressed peers.
AB  - Children's mental representations of situations involving another child's
      distress were examined in two studies. Study 1 examined 3- to 7-year-old
      children's (n= 44) ideas about what victims and bystanders would think, feel and
      do in hypothetical situations. In Study 2, 7- to 8-year-olds (n= 40) described
      their own cognitive response to situations in which they were confronted with
      another's distress. In both studies, representational bias was examined in
      relation to children's display of prosocial and aggressive behavior and in
      relation to their acceptance of distressed peers. Although not entirely
      consistent, findings indicate that three types of representational biases are
      associated with low levels of considerate behavior and with relatively low
      acceptance of distressed peers: (a) mentally representing the victim's problem
      without giving thought to its implications for the victim, (b) significantly
      reducing the emotional significance of the problem and (c) exaggerating negative
      aspects of the problem.

PMID- 17518914
TI  - Personality predicts prospective memory task performance: an adult lifespan
      study.
AB  - Do interindividual differences in prospective memory task performance reflect
      individual differences in personality and lifestyle? Do the cognitive abilities
      known to change with age retain their power to predict episodic prospective
      memory task performance after controlling for personality and lifestyle
      variables, and do personality and lifestyle variables offer predictive power
      apart from that provided by cognitive ability measures? To answer these
      questions, we conducted a study with community-living healthy individuals (n=
      141) between 18 and 81 years of age. They completed three different episodic
      prospective memory tasks--two laboratory tasks and one field task--as well as
      various measures of personality, lifestyle, and cognitive ability. The results
      indicated that personality and lifestyle reliably predicted who will succeed and
      who will fail on all three episodic prospective memory tasks. Conscientiousness
      predicted performance on two of the prospective memory tasks; socially prescribed
      perfectionism and neuroticism each predicted performance on one of the
      prospective memory tasks. Cognitive ability predicted performance on one of the
      laboratory prospective memory tasks but not on the other two prospective memory
      tasks. After we controlled for individual differences in personality and
      lifestyle variables, cognitive ability was no longer able to predict performance
      on the laboratory prospective memory task. By contrast, controlling for cognitive
      ability had no influence on the predictive power of the personality and lifestyle
      variables.

PMID- 17518915
TI  - Validation of a Swedish short self-report measure of core affect.
AB  - This research aimed at validating two self-report composite rating scales of core
      affect that are useful when quick assessments are required, for instance, of
      current mood or recalled, anticipated, and experienced emotional reactions. The
      ratings were derived from the Swedish Core Affect Scales (SCAS) comprising six
      self-report rating scales of the two orthogonal dimensions of core affect,
      valence (unpleasantness-pleasantness) and activation (quietness-excitement). In
      three samples of university students who were requested to rate current moods,
      affect-inducing sounds, or affect-inducing pictures, the composite ratings were
      compared to SCAS, two widely used graphical rating scales of valence and
      activation, and skin conductance responses and the acceleratory peak of heart
      rate. Three different rating formats were also compared. The results showed that
      the composite ratings were reliable and yielded the expected correlations with
      the other ratings and with the physiological affect indicators. No effects of
      rating format were detected. It is concluded that the composite ratings of
      valence and activation may be used if quick assessments are called for. Choices
      can be made of any of three rating formats depending on purpose with the
      assessments.

PMID- 17518916
TI  - Empathy, guilt, and gender: a comparison of two measures of guilt.
AB  - The relations of empathy with two measures of guilt were examined in a sample of
      13- to 16-year-olds (N= 113). Empathy was measured using Davis's IRI and guilt by
      Tangney's TOSCA and Hoffman's semi-projective story completion method that
      includes two different scenarios, guilt over cheating and guilt over inaction.
      Empathy correlated more strongly with both measures of guilt than the two
      measures correlated with each other. For boys, cognitive perspective-taking was a
      stronger predictor for guilt than for girls. Hoffman's guilt over inaction was
      more strongly associated with empathy measures in girls than in boys, whereas for
      guilt over cheating the pattern was the opposite. The results indicate that boys
      and girls may emphasize different aspects of morality.

PMID- 17518917
TI  - Socio-cognitive conflict, emotions and complexity of thought in real-life
      morality.
AB  - A new taxonomy of real-life dilemmas was tested in two studies. In Study 1, 35
      respondents assessed six types of real-life dilemmas in terms of socio-cognitive
      conflict. Support was found for a classification of dilemmas into three levels of
      socio-cognitive conflict. In Study 2, 191 young women responded to measures of
      social perspective-taking and emotional empathy and reported a real-life moral
      dilemma as well as their feelings while making decisions about it. The dilemmas
      were classified into personal and impersonal and into three levels of socio
      cognitive conflict. Dependent variables were the integrative complexity of the
      arguments and the reported feelings (sympathy, upset, and remorse). Dispositional
      empathy and perspective taking predicted level of socio-cognitive conflict and
      feelings of sympathy but not integrative complexity. Personal dilemmas aroused
      more feelings of upset than did impersonal ones. Low socio-cognitive conflict
      dilemmas evoked less complex thinking and less intensive feelings of upset and
      sympathy than did moderate and high socio-cognitive conflict dilemmas.

PMID- 17518918
TI  - Constructions of work stress and coping in a female- and a male-dominated
      department.
AB  - In the present study the nature of stress and coping was investigated and
      considered as socially constructed. Thirty small group interviews were performed
      using the Critical Incident Technique in one female- and one male-dominated
      customer service department of a telecom company. The main themes about stress
      among both women and men were often expressed as collective phenomena and were
      connected to the organizational change and downsizing process, problems when
      carrying out the work and lack of autonomy. However, a striking difference
      between female and male interviews was found in the way that women to a greater
      extent expressed lack of autonomy and their working situation was described as
      strictly regulated. The findings illustrate that a traditional gender difference
      regarding autonomy could be found when comparing a female- and a male-dominated
      department even though they were performing the same type of job. Both women and
      men portrayed coping as a mixture of collective and individual strategies. They
      often mentioned collective acceptance, resignation and hardening. There is a need
      for further research about women and men at work, taking into consideration the
      interpersonal context and the collective nature of stress and coping.

PMID- 17518919
TI  - Estimation of premorbid cognitive function based on word knowledge: the Swedish
      Lexical Decision Test (SLDT).
AB  - In clinical neuropsychology, the present status of a patient is evaluated in
      relation to the assumed premorbid status. However, in Sweden, existing methods to
      assess premorbid status are far from optimal. In the present study, the design
      and evaluation of a Swedish Lexical Decision Test (SLDT) for premorbid global
      cognitive function (i.e., premorbid intelligence) is described. The design was
      based on the empirical finding that, in general adult population, word knowledge
      is strongly associated with measures of global cognitive functioning. Linear
      stepwise regression analysis demonstrated that SLDT findings accounted for 48% of
      the variance of global cognitive function as assessed by the Full Scale
      Intelligence Quotient (FSIQ) from the Wechsler Adult Intelligence Scale Revised
      (WAIS-R). Demographic variables alone accounted for 31% and a combination of SLDT
      results and demographics accounted for 60%. Psychometric properties are presented
      using data from 109 healthy individuals stratified according to age, gender, and
      level of education. In addition, a case of Alzheimer's disease is presented to
      illustrate the relationship between SLDT performance and cognitive function.
      Finally, the theoretical foundation for the relationship between word knowledge
      and global cognitive function is discussed.

PMID- 17518920
TI  - Atypical performance: how do we deal with that?

PMID- 17518921
TI  - Neuromotor task training for children with developmental coordination disorder.

PMID- 17518922
TI  - Current approaches to intervention in children with developmental coordination
      disorder.

PMID- 17518923
TI  - Neuromotor task training for children with developmental coordination disorder: a
      controlled trial.
AB  - The aim of this study was to evaluate neuromotor task training (NTT), a recently
      developed child-centred and task-oriented treatment programme for children with
      developmental coordination disorder (DCD). A treatment and a non-treatment
      control group of children with DCD were included. Children were selected if they
      scored below the 15th centile on the Movement Assessment Battery for Children
      (MABC). The children in the treatment group were recently referred for
      physiotherapy (n=26; 20 males, 6 females; mean age 7y 2mo [SD 1y 3mo]). The
      parents of the non-treated children were concerned about their children's motor
      performance and responded to advertisements for free testing (n=13; 10 males, 3
      females; mean age 7y 2mo [SD 2y 1mo]). Before and after nine weekly 30-minute
      sessions of NTT or at least 9 weeks of no intervention, the MABC and the Test of
      Gross Motor Development - 2 (TGMD-2) were administered. Therapists reported per
      session on treatment goals and tasks trained. The results indicate that motor
      performance does not improve spontaneously and that NTT is effective. During the
      intervention period, only the treated group improved on the MABC and the TGMD-2.
      Children improved most on tasks similar to those trained. In older children with
      poorer motor patterns, NTT's treatment success was higher. The Child Behavior
      Checklist subscales withdrawn, thought problems, anxious/depressed, and
      delinquency were determinants of effects on motor patterns.

PMID- 17518924
TI  - Executive functioning in childhood epilepsy: parent-report and cognitive
      assessment.
AB  - There is considerable interest in the assessment of executive function (EF) in
      pediatric clinical populations but only a few well-standardized measures exist.
      We examined EF in 53 children aged 8 to 18 years with recent onset epilepsy (31
      males, 22 females) and 50 control children (23 males, 27 females) using the
      Behavior Rating Inventory of Executive Function (BRIEF) and the Delis-Kaplan
      Executive Function System (D-KEFS). Thirty children had localization-related
      epilepsy and 23 had idiopathic generalized epilepsy; average duration of 10
      months (SD 4y 1mo) and onset age of 11 years 6 months (SD 3y 6mo). The study
      sample was characterized by good seizure control, with 40 participants taking one
      antiepileptic drug (AED), one taking two AEDs, and 12 not treated
      pharmacologically. Children with epilepsy showed greater executive difficulties
      on both measures than children in the control group. The BRIEF and D-KEFS were
      significantly correlated, and an 'at-risk' group identified from the BRIEF was
      more significantly impaired on the D-KEFS than a 'low risk' group. The BRIEF was
      also a better predictor of performance on the D-KEFS than the Child Behavior
      Checklist. These findings indicate that children with recent onset epilepsy show
      significant difficulties in E F, and demonstrate the utility of parent ratings
      (BRIEF) in the assessment of EF.

PMID- 17518925
TI  - Clinical and radiological features of childhood cerebral infarction following
      varicella zoster virus infection.
AB  - The aim of the study was to describe the clinical and radiological features of
      childhood post-varicella cerebral infarction (PVCI). A retrospective review was
      undertaken of children with arterial ischaemic stroke (AIS) who had experienced
      varicella zoster virus (VZV) infection within the preceding year. Twenty-four
      children (15 males, nine females; age range at time of VZV infection 2mo-6y) were
      identified, with a median of 4 months between VZV and AIS (range 1wk-12mo). All
      had infarction in the middle cerebral artery (MCA) territory and abnormalities of
      the M1 segment; arteriopathy affected other arteries in 10 children. After a
      median of 27 months, six patients had recurrent transient ischaemic attacks
      (TIA), with new infarcts in two of 22 children on re-imaging. Arterial disease
      improved in 11 children, was stable in four, and progressed in seven (of whom
      four had recurrent TIA and two had re-infarction). PVCI affects young, previously
      healthy children within a few months of VZV infection and is characterized by MCA
      territory infarction and proximal MCA disease. One quarter of patients have
      recurrence, usually, but not inevitably, associated with progressive
      arteriopathy. Treatable co-existing AIS risk factors should always be excluded. A
      more comprehensive diagnostic evaluation should be considered in children with
      AIS who do not fit the clinical and radiological profile outlined, even where
      there is a history of recent VZV infection.

PMID- 17518926
TI  - Cerebrospinal fluid baclofen concentrations in patients undergoing continuous
      intrathecal baclofen therapy.
AB  - The aim of this study was to report concentrations of cerebrospinal fluid (CSF)
      baclofen in children undergoing chronic intrathecal baclofen (ITB) infusions. CSF
      baclofen concentrations were analyzed in 53 specimens obtained by intrathecal
      catheter aspiration from 43 participants (28 males, 15 females; range 3-44y, mean
      16y [SD 8y 11mo]), with functioning baclofen pumps and catheters. Daily ITB doses
      ranged from 70 to 1395 microg per day (mean 607 microg per day [SD 363], median
      575). Baclofen concentration was quantified by high-pressure liquid
      chromatography and confirmed by injection onto a gas chromatograph. CSF baclofen
      concentrations from children receiving either simple continuous or complex
      infusions ranged from 0.2 to 20.0 microg/ml (mean 4.64 microg/ml, median 3.3
      microg/ml). CSF baclofen concentrations from children receiving simple continuous
      infusions ranged from 0.5 to 12.9 (mean 4.7 microg/ml, median 3.55 microg/ml).
      There was no correlation between ITB dosage and CSF baclofen concentration. We
      conclude that baclofen concentration can be measured to determine if baclofen is
      present in CSF. However, there appears to be no correlation between the ITB dose
      infused and the corresponding CSF baclofen level.

PMID- 17518927
TI  - Hyoscine skin patches for drooling dilate pupils and impair accommodation:
      spectacle correction for photophobia and blurred vision may be warranted.
AB  - Hyoscine skin patches diminish salivation by their anticholinergic action. The
      aim of reporting this case series is to present the ophthalmic side effects in
      children, and to highlight the precautions to take. Five children (two males,
      three females; age range 8-18y) with quadraplegic cerebral palsy (Gross Motor
      Function Classification System Level V) and profound intellectual impairment,
      wearing hyoscine skin patches to control excessive salivation, were examined.
      Binocular visual acuity, pupil reaction, pupil diameter, and dynamic retinoscopy
      were recorded before and after instilling guttae cyclopentolate 1%. The
      accommodative responses were compared with the expected norms. Spectacle
      correction was provided for refractive error and to compensate for lack of
      accommodation. Tinted lenses were provided for photophobia. Visual assessment was
      repeated 6 months later. All children had dilated pupils with a mean diameter of
      7.8mm (range 7-9mm) before instilling guttae cyclopentolate. Mean pupil
      constriction to bright light was only 1.8mm (range 1-2mm). Mean resting
      accommodation was 0.45 dioptres (D; range 0-1D) and no accommodative responses
      were detected on dynamic retinoscopy. Three children were photophobic. Visual
      behaviour was seen to improve after the use of appropriate spectacles.
      Photophobia was relieved by tinted lenses. The anticholinergic effects of
      hyoscine skin patches can cause photophobia and impair vision due to pupil
      dilatation and paralysis of accommodation. Appropriate spectacles are
      recommended.

PMID- 17518928
TI  - Autoimmune diseases in parents of children with infantile autism: a case-control
      study.
AB  - This register study compared the rates and types of autoimmune disease in the
      parents of 111 patients (82 males, 29 females; mean age at diagnosis 5y 5mo [SD
      2y 6mo]) with infantile autism (IA) with a matched control group of parents of
      330 children from the general population. All parents were screened through the
      nationwide Danish National Hospital Register. We inquired about 35 autoimmune
      diseases during an observation period of 27 years. At follow-up the case and
      control mothers were identical in age (65y 7mo [SDs 9y 7mo and 9y respectively]).
      For case and control fathers the figures were 70 years 2 months (SD 10y 2mo) and
      69 years 1 month (SD 10y 1mo) respectively. A similar proportion of case and
      control mothers had a diagnosis of any autoimmune disease: 10.8% versus 9.1%. For
      case fathers the proportion was 8.6% versus 4.6%. Two autoimmune conditions were
      associated with IA: ulcerative colitis in mothers (p=0.05) and type 1 diabetes in
      fathers (p=0.02). Additional studies are required to determine whether there is a
      true association between a parental history of autoimmune disease and pervasive
      developmental disorder in their offspring.

PMID- 17518929
TI  - Reduced parietal and visual cortical activation during global processing in
      Williams syndrome.
AB  - Several lines of investigation suggest that individuals with Williams syndrome
      (WS), a neurodevelopmental disorder of well-characterized genetic etiology, have
      selective impairments in integrating local image elements into global
      configurations. We compared global processing abilities in 10 clinically and
      genetically diagnosed participants with WS (eight females, two males; mean age
      31y 10mo [SD 9y 7mo], range 15y 5mo-48y 4mo) with a typically developed (TD) age-
      and sex-matched comparison group (seven females, one male; mean age 35y 2mo [SD
      10y 10mo], range 24y-54y 7mo) using functional magnetic resonance imaging (fMRI).
      Behavioral data showed participants with WS to be significantly less accurate
      (p<0.042) together with a non-significant trend to be slower than the TD
      comparison group while performing the global processing task. fMRI data showed
      participants with WS to possess reduced activation in the visual and parietal
      cortices. Participants with WS also showed relatively normal activation in the
      ventral occipitotemporal cortex, but elevated activation in several posterior
      thalamic nuclei. These preliminary results largely confirm previous research
      findings and neural models implicating neurodevelopmental abnormalities in
      extended subcortical and cortical visual systems in WS, most notably dorsal
      stream pathways.

PMID- 17518930
TI  - Effects of oral stimulation and oral support on non-nutritive sucking and feeding
      performance in preterm infants.
AB  - This study compared the effects of oral stimulation with those of oral support on
      non-nutritive sucking and feeding parameters in preterm infants. Preterm infants
      (23 males, 20 females) born between 29 and less than 34 weeks' gestational age
      (GA; mean GA 31.2wks [standard error of mean{SEM} 0.39]; mean birth-weight 1580g
      [SEM 120]) were allocated to one of three experimental groups:
      (Stimulation+support [five males, four females]; Stimulation [four males, seven
      females]; and Support [seven males, five females]) or a control group. Non
      nutritive sucking pressure and sucking activity were quantified in the gavage and
      transition periods. Oral support minimizes fluid loss, stabilizes the jaw, and
      organizes deglutition. The time of transition, the quantity of milk ingested per
      day, and the number of bottle feeds per day were recorded. Variables were
      analyzed by repeated-measures analysis of variance, with birth-weight as
      covariate (ANCOVA). Transition time was reduced (p<0.0001) for the
      Stimulation+support and Support groups. ANCOVA computed during gavage showed
      increased non-nutritive sucking pressure and sucking activity (p<0.001) for the
      Stimulation and Stimulation+support groups. ANCOVA computed during transition
      revealed increases in non-nutritive sucking pressure and daily bottle feeds
      (p<0.001) for the three experimental groups and in daily milk ingested (p=0.002)
      for the Stimulation+support and Support groups. We demonstrated that oral support
      is the result of both the action of chin and cheek support, and the aid to
      deglutition. An analysis of the organization of sucking patterns should be
      undertaken to provide better understanding of the mechanisms involved in oral
      support.

PMID- 17518931
TI  - Being in pain: a phenomenological study of young people with cerebral palsy.
AB  - This study explored the experience and impact of chronic pain on the lives of
      adolescents and young adults with cerebral palsy (CP). Six participants with CP
      (four males, two females; age range 14-24y) who were known to experience chronic
      pain participated in individual in-depth interviews. Five participants had
      quadriplegia and used wheelchairs; one had left hemiplegia and walked
      independently. Pain was located in the hips, back, bladder, and upper limbs.
      Interviews were analyzed using a six-step phenomenological process. Participants
      in the study were found to live with constant pain that was difficult to relieve
      and pervaded their lives. They often felt isolated and became frustrated due to
      their loss of independence and inability to participate in activities.
      Participants indicated the importance of having their experience of pain
      acknowledged, supporting the need for greater attention to ongoing holistic
      management. Further research into effective interventions may enable increased
      activity participation and prevent later chronicity.

PMID- 17518932
TI  - Physical and sedentary activity in adolescents with cerebral palsy.
AB  - Participation in regular physical activity (PA) provides health, psychological,
      and physiological benefits for people with and without a physical disability.
      This study investigated the physical and sedentary activity patterns of
      adolescents with cerebral palsy (CP). A cross-sectional, descriptive, postal
      survey was used, consisting of the Physical Activity Questionnaire for
      Adolescents (PAQ-A), self-reported level of gross motor function (based on the
      Gross Motor Function Classification System [GMFCS]), and specific questions
      regarding weekly sedentary activities. Following piloting to determine test
      retest reliability (intraclass correlation [ICC] for PA=0.90; total weekly
      sedentary time=0.84) and concurrent validity (survey PA score vs pedometry,
      Pearson's r=0.24; survey PA score vs accelerometry, r=-0.21; survey weekly
      sedentary time vs logbook, r=0.38), the survey was mailed to all adolescents with
      CP in South Australia registered with Novita Children's Services (n=219). One
      hundred and twelve valid surveys were returned (76 males, 36 females; age range
      11-17y, mean age 13y 11mo [SD 23mo]; GMFCS Level I, n=42; Level II, n=27; Level
      III, n=10; Level IV, n=17; Level V, n=15; level not reported, n=1). Results were
      compared with recent normative age- and sex-matched data sets. Key findings were
      that PA level of adolescents with CP was related to level of gross motor function
      and inversely related to age, and that adolescents with CP were less physically
      active than their peers without disability. Comparisons with normative data sets
      suggested that adolescents with CP tend to participate in less structured and
      lower intensity PA compared with non-disabled adolescents, though sedentary
      activity patterns (TV and computer use) of adolescents with and without CP were
      similar.

PMID- 17518933
TI  - Life satisfaction of young adults with spina bifida.
AB  - This study concerns life satisfaction and its determinants in Dutch young adults
      with spina bifida (SB). Data on life satisfaction (Life Satisfaction
      Questionnaire [LiSat-9]) were related to hydrocephalus, lesion level,
      disabilities, and demographic variables. In total, 179 young adults with SB
      participated (41% male, age range 16-25y; 79% SB aperta, 67% hydrocephalus [HC],
      39% wheelchair-dependent). Most were satisfied with their life as a whole (24%
      dissatisfied). No difference was found from a population reference group (28%
      dissatisfied). Highest proportions of dissatisfaction were found for financial
      situation (44%), partnership relations (49%), and sex life (55%). Least
      dissatisfaction was found for contact with friends (17%) and families (15%).
      Young adults with SB and HC were more satisfied with their financial situation
      and family life but were less satisfied with self-care ability and partnership
      relations than those without HC and the reference group. However, except for self
      care ability, relationships between life satisfaction and having SB were weak. In
      conclusion, self-care ability and partnership relations were rated least
      favourable and may need more attention from care providers. Overall, SB does not
      seem to be an important determinant of life satisfaction.

PMID- 17518934
TI  - Aicardi syndrome associated with anterior cephalocele in a female infant.
AB  - Aicardi syndrome is a triad of abnormalities that includes total or partial
      agenesis of the corpus callosum, chorioretinal lacunae, and infantile spasms.
      This syndrome was first described in 1965. A female infant with Aicardi syndrome
      associated with a nasoethmoidal cephalocele is described in this report. She
      presented with a history of unilateral nasal discharge since birth and seizures
      since age 1 week. She was microcephalic and there was visual impairment. A fleshy
      mass of the left nostril was noted. Ophthalmological evaluation revealed left
      exotropia, dysplastic optic discs and retina, 'morning glory' appearance of the
      left optic disc, and bilateral chorioretinal lacunae. Magnetic resonance imaging
      of the brain showed absence of the corpus callosum, dysmorphic changes of the
      lateral ventricles, a superiorly located third ventricle, heterotopic grey matter
      of the frontal lobes, a left nasoethmoidal cephalocele, and closed lip
      schizencephaly of the left frontal lobe. This female infant developed asymmetric
      infantile spasms at age 8 weeks. Surgical correction of the cephalocele was
      declined. She developed recurrent pneumonias secondary to aspiration of feeds and
      died at age 8 months during one of these events.

PMID- 17518935
TI  - Current approaches to intervention in children with developmental coordination
      disorder.
AB  - This review analyzes approaches to intervention in children with developmental
      coordination disorder within the framework of how children develop and learn
      motor skills, drawing upon maturational, cognitive, and dynamic systems models.
      The approaches to intervention are divided into two categories: (1) process or
      deficit-oriented approaches; and (2) approaches that teach specific functional
      skills. These approaches are viewed alongside theoretical, empirical, and
      experiential standpoints, noting the differences and the fact no single approach
      is, as yet, fully substantiated. Principles and guidelines are drawn from the
      analyses that support both cognitive and dynamic models and that are set within
      an ecological framework.

PMID- 17518938
TI  - 'Sex, neuroprotection, and neonatal ischemia'.

PMID- 17518939
TI  - 'Long-term survival in X-linked myotubular myopathy'.

PMID- 17518942
TI  - Unassisted pelvic floor exercises for postnatal women: a systematic review.
AB  - AIM: This paper is a report of a systematic review on unassisted pelvic floor
      exercises for postnatal stress incontinence to identify effective interventions
      and highlight areas for further research. BACKGROUND: Stress incontinence is a
      common and embarrassing problem. Childbirth is a major cause and problems can be
      persistent for some. However women are often reluctant to seek help. METHOD: We
      conducted a systematic literature search in December 2006 using the CINAHL,
      Medline and Cochrane Library databases, hand-searching of selected textbooks,
      checking reference lists and contacting experts. There were no date restrictions.
      The review included randomized controlled trials, published in English, of
      unassisted pelvic floor exercises in postnatal women. Two reviewers independently
      extracted data and assessed study quality. Main outcomes were reduction in
      symptoms of incontinence, patient satisfaction and quality of life. RESULTS: Four
      randomized controlled trials met the inclusion criteria. Interventions ranged
      from written information to structured exercise classes, while usual care varied
      from a leaflet to group sessions with a midwife. Three out of four studies
      demonstrated short-term improvement in incontinence symptoms, which was
      statistically significant in two. However, at later follow-up there was no longer
      a statistically significant effect on continence. All trials found that women in
      the intervention group were more likely to do the exercises. CONCLUSION: We found
      few trials, quality was variable, and comparisons were difficult because of
      variations in interventions and outcomes measured. Further high quality
      evaluations are needed, using standardized interventions and outcome measures,
      patient-relevant outcomes such as quality of life, and follow-up periods that
      enable evaluation of long-term effectiveness.

PMID- 17518943
TI  - In response to: Kitson A. (2006) The relevance of scholarship for nursing
      research and practice. Journal of Advanced Nursing 55(5), 541-545.

PMID- 17518946
TI  - Atypical cutaneous leishmaniasis cases display elevated antigen-induced
      interleukin-10.
AB  - In humans, Leishmania chagasi parasites can produce subclinical infections,
      atypical cutaneous leishmaniasis (ACL) and visceral leshmaniasis that is
      potentially fatal if not treated in a timely fashion. L. chagasi parasites that
      cause both ACL and visceral disease appear to be genetically similar, which
      suggests that host factors such as the immune response play an important role in
      controlling infection. We evaluated the immunologic response in ACL using
      peripheral blood mononuclear cells (PBMCs) of 37 subjects divided into three
      groups: (i) active ACL cases, (ii) asymptomatic cases and (iii) persons with no
      history of Leishmania infection. The supernatants of stimulated PBMCs were
      analysed for production of IL-10, IFN-gamma and IL-2. Robust production of IL-10
      in response to Leishmania stimulation was observed in active ACL cases, compared
      to low levels in asymptomatic cases and negative controls. Serum IgE levels,
      measured by ELISA, were not significantly different among the three groups. In
      addition, ACL cases displayed depressed levels of all cytokines in response to
      mitogen. Thus, this first characterization of the immune response in ACL suggests
      a role for IL-10 as well as partial immunosuppression.

PMID- 17518947
TI  - Reduced apoptosis in BALB/c mice infected with Heligmosomoides polygyrus.
AB  - We evaluated levels of apoptosis and the immune response ex vivo in BALB/c mice
      infected with Heligmosomoides polygyrus. Cell proliferation, apoptosis and
      cytokine production were measured in mesenteric lymph nodes (MLN) without
      exposure to H. polygyrus antigens in culture. The inhibited apoptosis and
      cytokine production reported might reflect a state of cell hyporesponsiveness in
      the prepatent phase of infection. These changes were accompanied by changes in
      the percentage of CD4+ cells in MLN and popliteal lymph nodes (PLN). The
      prolonged reduction in apoptosis coexisted with induced cell proliferation,
      elevated TNF-alpha, IL-12p70, IFN-gamma, IL-6, IL-10 and TGF-beta synthesis, but
      lowered IL-4 and IL-2 levels. In the chronic phase of infection an increasing
      production of IFN-gamma, monocyte chemotactic protein-1 (MCP-1), IL-10 and TGF
      beta with decreasing concentrations of other cytokines resulted in restored
      apoptosis. The cytokine response in serum showed moderate production of TNF
      alpha, temporary involvement of IL-12p70, induction of IFN-gamma and IL-10
      synthesis, as well as growing IL-6 and MCP-1 production. It is suggested that a
      synchronized synthesis of distinct cytokines is accompanied by different levels
      of inhibited apoptosis during the prepatent and chronic phases of H. polygyrus
      infection in BALB/c mice. We suggest that immunosuppression provoked by the
      nematode is not the outcome of parasite-induced apoptosis, but rather results
      from a hyporesponsiveness experienced by cells during H. polygyrus infection.

PMID- 17518948
TI  - Role for CTLA-4 but not CD25+ T cells during Schistosoma mansoni infection of
      mice.
AB  - Schistosoma mansoni infection of mice increases the frequency of cells that are
      CD4+ CD25+ in the acute (4 and 8 weeks) and chronic (16 week) stages of
      infection. Depletion of > 85% of CD25+ cells in the acute or chronic stages of
      schistosome infection caused no overt changes in morbidity or immunological
      responses. The absence of effect in mice with CD25+ cells depleted may be due to
      the preferential expression of IL-4 and IL-10, two cytokines that are protective
      in schistosome infection, on CD25- CD4+ cells. We also assessed infection-induced
      changes of other regulatory markers, GITR, CD103 and CTLA-4 on CD4+ cells. We
      identified a marked expansion of CTLA-4+ population on CD25- CD4+ cells in acute
      and chronic infection. Blocking of CTLA-4 during acute, but not chronic
      infection, caused significant weight loss and altered the type 2 cytokine
      response of mice, with increased IL-4 and IL-5 production associated with
      significantly more Th2 cells and eosinophils in the liver granuloma. This study
      illustrates the complexity of regulation of T cells in schistosome infection and
      highlights a specific role for CTLA-4+, but not CD25+ cells, in the regulation of
      Th2 responses in helminth infection.

PMID- 17518949
TI  - A longitudinal study of immune responses to Plasmodium falciparum sexual stage
      antigens in Tanzanian adults.
AB  - Next to children, adults form a substantial part of the infectious reservoir that
      is responsible for the spread of malaria. In this longitudinal study, we
      determined sexual stage immune responses to Plasmodium falciparum and
      infectiousness to mosquitoes in adults from an area with intense malaria
      transmission. A cohort of 43 Tanzanian adults was followed for 18 months.
      Parasitological data were collected monthly; serum once every three months.
      Antibody prevalences were determined for sexual stage antigens Pfs230 and
      Pfs48/45 and circumsporozoite protein (NANP5)(n = 199). Functional transmission
      reducing activity (TRA) was assessed by standard membrane feeding assay (SMFA; n
      = 85). Cumulative parasite prevalence was 67.4% (29/43) for asexual stages and
      34.9% (15/43) for gametocytes. Enrolment antibody prevalence was 95.3% (41/43)
      for NANP5, 18.9% (7/37) for Pfs230 and 7% (3/43) for Pfs48/45 epitope 3. TRA >
      50% reduction was seen in 48.2% (41/85) and TRA > 90% reduction in 4.7% (4/85) of
      the samples. Our findings of low and inconsistent sexual stage immune responses
      are likely to be the result of a low exposure to gametocytes in this older age
      group. This may in turn be caused by effective asexual stage immunity. We
      conclude that the infectivity of older individuals is less likely to be affected
      by sexual stage immunity.

PMID- 17518950
TI  - Vaccination of goats with recombinant galectin antigen induces partial protection
      against Haemonchus contortus infection.
AB  - The efficacy of vaccination against Haemonchus contortus infection with two
      recombinant proteins, rHco-gal-m and rHco-gal-f, was studied in 9-10-month-old
      goats. Vaccination with 100 microg protein reduced faecal egg output and worm
      burdens by 37.25% and 41.1%, respectively. Corresponding reductions with 200
      microg protein were 48.03% and 46.19%. Vaccinated groups had significantly higher
      IgG levels than the negative and positive controls. Significant negative
      correlations were detected between IgG level, mucosal homogenate IgA
      concentration, haemoglobin and abomasal worm burden at necropsy. By contrast a
      positive correlation was found between the percentage of B cells, monocytes and
      abomasal worm burden. These findings suggested that vaccination with a
      combination of recombinant rHco-gal-m/f proteins had a role in protecting goats
      against H. contortus infection.

PMID- 17518952
TI  - Dementia, oral health and the failing dentition.

PMID- 17518951
TI  - Trichuris suis excretory/secretory antigen-specific antibodies in serum from
      single-inoculated pigs.
AB  - The humoral immune response induced by Trichuris infections has mostly been
      described in mouse models and in infected humans, but as the immunomodulatory
      effect of Trichuris suis, the swine whipworm, becomes increasingly documented,
      the need for understanding the response induced by this specific parasite species
      grows. In the present study we describe changes in serum IgG1, IgG2, IgA and IgM
      antibodies specific to adult T. suis excretory/secretory (E/S) antigens in the
      time course of a primary infection in swine. The average levels of specific IgG1,
      IgG2 and IgM peaked at 9 weeks post-inoculation and then declined within a few
      weeks of worm expulsion. The IgA level rose earlier and remained elevated after
      worm expulsion. The protective role of Trichuris-specific antibodies is
      uncertain, but some of them presumably reflect the presence of worms in the
      intestine. Further development of this analysis could have diagnostic value in
      swine and humans infected with T. suis for experimental or therapeutic purposes.

PMID- 17518953
TI  - Oral health conditions of community-dwelling cognitively intact elderly persons
      with disabilities.
AB  - OBJECTIVES: To present descriptive information on oral health and health care of
      community-dwelling elderly persons with disabilities who are living at home.
      BACKGROUND: Most previous studies have focused on specific subpopulations,
      namely, persons who are essentially healthy and independent, are homebound, or
      are nursing home residents. Little information appears to be available on
      community-residing elderly persons with disabilities. MATERIALS AND METHODS: A
      total of 641 participants aged 65 years and over in a Medicare Demonstration who
      were cognitively intact, completed an oral health questionnaire within 1 year of
      Demonstration entry. Demonstration participants were required to be living in the
      community, need or receive help with 2+ activities of daily living (ADLs) or 3+
      instrumental ADLs (IADLs), and have recently experienced significant health
      services utilisation. RESULTS: Subject mean age was 79.1 years, 73.8% were
      female, and 4% were minority. They were dependent in a mean of 1.8 ADLs and 2.9
      IADLs. 43.1% reported that they had no natural teeth, 77.4% had dentures, 58.8%
      frequently felt their mouth was dry, 5.2% had jaw pain now and 6.1% had at some
      time experienced burning sensations in their mouth or tongue. 40.4% reported that
      they were currently in need of dental treatment, although 56.2% indicated they
      now had a dentist, and 42.1% identified having a dental visit within the past 12
      months. 19.7% indicated some dental insurance coverage. CONCLUSION: This is one
      of the first studies to focus on community-dwelling elderly people with
      disabilities. Substantial oral health morbidity was reported.

PMID- 17518954
TI  - Patient ratings of chewing ability from a randomised crossover trial: lingualised
      vs. first premolar/canine-guided occlusion for complete dentures.
AB  - BACKGROUND: Complex procedures involving a facebow transfer and the use of
      lingualised teeth are deemed to have a positive influence on the chewing ability
      with complete dentures. OBJECTIVES: To determine if patients' ratings of their
      ability to chew depend on the method of complete denture fabrication. METHODS:
      Edentulous patients (n = 20) participated in a within-subject crossover trial.
      Each patient received two sets of new complete dentures. One pair was
      manufactured based on intraoral tracing of centric relation and facebow transfer;
      semi-anatomical teeth with lingualised occlusion denture (LOD) were chosen. The
      second pair was made using a simplified procedure without facebow transfer; jaw
      relations were recorded with wax occlusion rims, and anatomical teeth with a
      first premolar/canine-guidance (CGD) were selected. The dentures were delivered
      in randomised order, and each was worn for 3 months. Three months after delivery,
      patients' ratings of each new prosthesis were recorded on visual analogue scales
      for their ability to chew seven index foods. Repeated measurements analysis of
      variance was performed to investigate possible carry-over effects accounting for
      confounding by treatment period. RESULTS: When comparing the two treatments,
      participants rated their ability to chew in general, to masticate carrots, hard
      sausage, steak and raw apple in particular, was significantly better with the CGD
      (anatomical teeth) than with the LOD (p < 0.05). CONCLUSION: Comprehensive
      methods for the fabrication of complete dentures including semi-anatomical
      lingualised teeth and a full registration do not seem to influence the perceived
      chewing ability, when compared with more simple procedures. Chewing ability for
      tough foods appears to benefit from the use of anatomical teeth.

PMID- 17518955
TI  - Association of total tooth loss with smoking, drinking alcohol and nutrition in
      elderly Japanese: analysis of national database.
AB  - OBJECTIVE: Various factors may be associated with edentulism in elderly people.
      Association of total tooth loss with smoking, alcohol intake and nutrition in non
      institutionalised elderly Japanese was assessed utilising national database.
      MATERIALS AND METHODS: Records of independent surveys, the Survey of Dental
      Diseases (SDD) and the National Nutrition Survey (NNS) in 1999 were
      electronically linked using the household identification number. RESULTS: Among
      the records of 6903 subjects in the SDD and 12 763 subjects in the NNS, 6805
      records were successfully linked. Overall, prevalence of total tooth loss in
      adults was very similar in males and females at approximately 7.0%, and the
      smoking rate was 47.6% and 9.9% respectively. Total tooth loss was a rare
      phenomenon (<2%) in age groups of <60 years. According to the multiple logistic
      regression analysis involving 2200 subjects aged 60 years or older, significant
      variables were age, current smokers and vitamin C intake in males, and age and
      current smokers in females. The variable for current drinkers was significant in
      females but the odds ratio was <1.0. No significant relationship was detected
      with respect to former smokers and drinkers, body mass index, vitamin E intake
      and blood glucose level. CONCLUSIONS: Current smoking was associated with total
      tooth loss, although smoking rate was low in females. Gender difference in the
      association was suggestive with respect to drinking alcohol and vitamin C intake.

PMID- 17518956
TI  - Edentulousness and associated risk factors in a south Brazilian elderly
      population.
AB  - AIM: To examine the relationship between edentulousness and the socioeconomic and
      behavioural variables collected in a cross-sectional study of an elderly
      population. METHODS: The study was conducted on 277 elderly (60 years or older)
      in the municipality of Biguacu, Southern Brazil. The oral examinations and
      questionnaires were conducted by two calibrated dentists. The criteria used
      followed the WHO and FDI standards. RESULTS: Prevalence of edentulousness reached
      48.4%. A significant association was found in bivariate analysis for gender,
      satisfaction with appearance, time since last dental visit, the type of dental
      service sought in the last 5 years, educational level of the elderly and their
      children, and age of the elderly. In the multivariate analysis, gender, time
      since last dental visit and level of education of the elderly were significantly
      associated with edentulousness. CONCLUSIONS: Female sex and low educational level
      were the main risk factors for edentulousness in this population. Although
      various Brazilian studies suggest a decline in edentulousness in the country,
      methodologically robust research into edentulousness in Brazil is still limited,
      demanding further studies into this highly prevalent yet preventable health
      problem amongst the elderly.

PMID- 17518958
TI  - Electromyographic evaluation of masseter and anterior temporalis muscles in rest
      position of edentulous patients with temporomandibular disorders, before and
      after using complete dentures with sliding plates.
AB  - OBJECTIVES: This study was performed with the purpose of investigating
      electromyographic (EMG) activity of the anterior temporalis and masseter muscles
      in edentulous individuals with temporomandibular disorder (TMD), before and after
      using sliding plates on complete dentures in the mandibular rest position.
      BACKGROUND: Edentulous patients may present TMD, which is characterised by pain
      in temporomandibular joints, masticatory and neck muscles, uncoordinated and
      limited mandible movements, joint sounds and an altered occlusal relationship. It
      is imperative to offer treatment in order to re-establish stomatognathic system
      structures before submitting the individual to any definitive restorative
      treatment. MATERIALS AND METHODS: The patients were edentulous for at least 10
      years. EMG recordings were made before the insertion of the dentures (0 months)
      and also after using the sliding plates at the fourth month, 9th month and 12th
      month, using computerised electromyography K6-I/ EMG Light Channel Surface. EMG
      evaluations of the muscles were performed under the following clinical
      conditions: rest position with dentures (R1), rest position without dentures
      (R2), rest position with dentures post-activity (chewing) (R3), rest position
      without dentures post-activity (chewing) (R4). RESULTS: All patients obtained
      remission of muscular fatigue and reduced pain in stomatognathic system
      structures. Temporalis muscle showed significant increase in EMG activity
      compared with initial values (p < 0.01). Masseter muscles showed significantly
      lower mean values (p < 0.01) compared with initial values. CONCLUSION: The
      sliding plates allowed the process of neuromuscular deprogramming, contributing
      to muscular balance of the masticatory system, and are therefore indicated to be
      used before the fabrication of definitive complete dentures in patients with TMD.

PMID- 17518957
TI  - Buffering effect of a prophylactic gel on dental plaque in institutionalised
      elderly.
AB  - OBJECTIVES: The effect of multiple daily applications of a prophylactic gel, with
      buffering substances, on plaque acidogenicity in elderly institutionalised
      individuals was evaluated. BACKGROUND: Many elderly suffer from reduced salivary
      flow, poor oral hygiene and increased levels of cariogenic bacteria and are
      considered to be at an increased risk for coronal and root caries. Reinforcing
      the buffering capacity of dental plaque by the addition of substances such as
      bicarbonate and phosphates may decrease their caries activity. MATERIALS AND
      METHODS: Fourteen elderly, with subjective dry mouth, were treated for 16-day
      periods at random with: (i) Profylin fluoride gel with buffering components; (ii)
      Profylin fluoride gel without buffering components and (iii) rinsing with water.
      Applications were made four times a day and each period was followed by a 2-week
      wash-out period. The plaque pH was registered after a carbohydrate challenge and
      the following were recorded before and after each test period: stimulated
      salivary secretion rate, buffer capacity, number Colony Farming Units (CFU)
      mutans streptococci, lactobacilli and a sample of Candida albicans on oral
      mucosa. RESULTS: Eleven participants (mean age 76.6 years) fulfilled the study.
      Changes in plaque pH measurements, when calculated as area under the curve
      (AUC(6.2) and AUC(5.7)) values (pH x min), before and after each of the three
      treatments, showed no significant differences. A tendency to a higher plaque
      acidogenicity and amount of cariogenic microorganisms was found after the gel
      treatments. C. albicans was found in low levels. CONCLUSION: Frequent
      applications of the gel did not result in an improved neutralising effect in the
      elderly. This may be caused by a combination of several factors, such as the
      level of oral dryness of the individuals and low solubility, release and
      retention of the gel substances in plaque. Instead, an increased plaque
      acidogenicity was noted.

PMID- 17518959
TI  - Comparison of surface electromyographic (sEMG) activity of submental muscles
      between the head lift and tongue press exercises as a therapeutic exercise for
      pharyngeal dysphagia.
AB  - OBJECTIVE: The present study compared surface electromyographic (sEMG) activity
      obtained from the submental muscle group for a tongue press and a head lift
      exercise as potential therapeutic exercises for dysphagic elderly. MATERIALS AND
      METHODS: Fifty-three healthy volunteers with a mean age of 35.3 participated in
      this study. Subjects were required to perform an isometric task, pressing their
      tongue against the hard palate, and an isotonic task requiring sustained lingual
      force against the hard palate. Pressure sensors were used to measure the amount
      of lingual pressure against the hard palate. Submental sEMG data from these tasks
      were compared with those obtained from the isometric and isotonic aspects of a
      head lift exercise. RESULTS: No sEMG differences were identified between the
      isometric tongue press task and head lift exercise. Isotonic tongue press
      exercises resulted in significantly higher maximum and mean sEMG values compared
      with the isotonic head lift exercise (p < 0.05). The submental sEMG activity from
      the tongue press exercise was equal (isometric) to, or greater (isotonic) than
      comparable muscle activation obtained during the head lift exercise. CONCLUSIONS:
      The tongue press exercise may be less strenuous than the head lift exercise while
      achieving the same therapeutic effect.

PMID- 17518960
TI  - Denture loss: an 8-month study in a community dental setting.
AB  - OBJECTIVE: Lost dentures can be a frustrating scenario for both patients and
      clinicians. This study aimed to find out where dentures were being lost and the
      level of assistance patients received with denture care. RESULTS: The results
      showed most dentures were lost in the hospital environment, and in many cases
      patients were not provided with pots in which to store their dentures or offered
      help or advice on denture care. The provision of new dentures to this patient
      group is complicated by the fact that in many cases the dentures were over ten
      years old and many of the patients were over eighty five years old. This makes
      adaptation to new dentures difficult. CONCLUSIONS: It is imperative that
      protocols are developed and staff trained to minimise the risk of lost dentures
      and improve the standard of denture care.

PMID- 17518961
TI  - Pharyngeal actinomycosis: a case report.
AB  - Actinomycetes are saprophytic bacteria of the oral cavity. They can produce a
      rare, chronic, and suppurative process that usually originates from the teeth and
      mandible and then involve the cervical region, especially in the sub-mandibular
      area. A case of actinomycosis occurring in the retropharyngeal space in a 74 year
      old man is reported. It arose as a swelling behind the third lower left molar
      that had no lesion. The patient was treated successfully with antibiotic therapy.
      The clinical presentation and management of the case are discussed and the
      relevant literature is reviewed.

PMID- 17518962
TI  - The contributions of qualitative research towards dental public health practice.
AB  - Dental public health (DPH) researchers have traditionally relied on quantitative
      methods for scientific enquiry. This paper argues that qualitative methodology
      can make a significant contribution to DPH knowledge and practice because it
      allows researchers to answer important questions of relevance to procedure and
      policy that are difficult to answer satisfactorily using quantitative methods
      alone. Qualitative research can also challenge the norms and assumptions of DPH
      practice. There are tensions in the relationship between qualitative research and
      the prevailing paradigm of evidence-based practice (EBP) which potentially
      influence the utility of DPH-related qualitative research. However, the relevance
      of qualitative research is increasing as the scope of EBP enquiry extends beyond
      questions of effectiveness, and methods are developed for incorporating
      qualitative research into systematic reviews.

PMID- 17518964
TI  - Is the Child Perceptions Questionnaire for 11-14 year olds sensitive to clinical
      and self-perceived variations in orthodontic status?
AB  - OBJECTIVES: To assess the association between scores on the Child Perceptions
      Questionnaire for 11-14 year olds (CPQ11-14) and clinical and self-perceived
      measures of malocclusion. METHODS: Children were recruited from an orthodontic
      clinic just prior to starting orthodontic treatment. They completed a copy of the
      CPQ11-14 and a short questionnaire concerning their feelings about the condition
      of their teeth. Study models were taken and rated according to the Dental
      Aesthetic Index (DAI) and the Peer Assessment Rating (PAR) index by two sets of
      three examiners. Intra and inter-rater reliabilities for the two sets of
      examiners ranged from 0.80 to 0.99. CPQ11-14 scores were calculated for the full
      35-item version and for 16 and 8-item short forms by summing the item response
      codes. The association between these scores, the DAI and PAR ratings and self
      perceived measures of malocclusion were examined using appropriate parametric and
      nonparametric tests. RESULTS: Complete data were collected for 141 children, 63
      boys and 78 girls. The mean age was 12.5 (SD = 1.0). DAI scores ranged from 17.0
      to 58.0 with a mean of 35.0 (SD = 8.0). The distribution of subjects across the
      four severity categories was minor/none - 6.6%, definite - 35.2%, severe - 15.6%
      and handicapping 42.6%. PAR scores ranged from 8.0 to 66.0 with a mean of 31.4
      (SD = 11.1). Eight percent had scores of 50 or above indicating marked deviation
      from an ideal occlusion. Both the long and the short forms of the CPQ11-14
      identified substantial variability in the impacts of malocclusion. Correlations
      between CPQ11-14 scores and the orthodontic indices ranged from 0.26 to 0.31 (P <
      0.01). There was a clear gradient in CPQ11-14 scores across four categories of
      the PAR based on quartiles. The gradient across the DAI categories was less
      clear. There were significant associations between all CPQ11-14 scores and the
      children's self-ratings of oral health, ratings of the extent to which the
      condition of the teeth affected life overall and expressions of happiness with
      the appearance and arrangement of the teeth. CONCLUSION: The results provide some
      evidence of the validity of the CPQ11-14 when used with children needing
      orthodontic treatment. However, because clinical samples are biased the study
      needs to be repeated in different treatment settings in order to confirm the
      utility of the measure.

PMID- 17518963
TI  - The International Caries Detection and Assessment System (ICDAS): an integrated
      system for measuring dental caries.
AB  - This paper describes early findings of evaluations of the International Caries
      Detection and Assessment System (ICDAS) conducted by the Detroit Center for
      Research on Oral Health Disparities (DCR-OHD). The lack of consistency among the
      contemporary criteria systems limits the comparability of outcomes measured in
      epidemiological and clinical studies. The ICDAS criteria were developed by an
      international team of caries researchers to integrate several new criteria
      systems into one standard system for caries detection and assessment. Using ICDAS
      in the DCR-OHD cohort study, dental examiners first determined whether a clean
      and dry tooth surface is sound, sealed, restored, crowned, or missing.
      Afterwards, the examiners classified the carious status of each tooth surface
      using a seven-point ordinal scale ranging from sound to extensive cavitation.
      Histological examination of extracted teeth found increased likelihood of carious
      demineralization in dentin as the ICDAS codes increased in severity. The criteria
      were also found to have discriminatory validity in analyses of social, behavioral
      and dietary factors associated with dental caries. The reliability of six
      examiners to classify tooth surfaces by their ICDAS carious status ranged between
      good to excellent (kappa coefficients ranged between 0.59 and 0.82). While
      further work is still needed to define caries activity, validate the criteria and
      their reliability in assessing dental caries on smooth surfaces, and develop a
      classification system for assessing preventive and restorative treatment needs,
      this early evaluation of the ICDAS platform has found that the system is
      practical; has content validity, correlational validity with histological
      examination of pits and fissures in extracted teeth; and discriminatory validity.

PMID- 17518965
TI  - Methodological assessment of behavioural problem dimensions in adults with dental
      fear.
AB  - OBJECTIVES: In the assessment and treatment of persons with dental fear, there
      may be other psychological/behavioural factors than fear itself and traditional
      measures of psychopathology that should be considered. Longitudinal natural
      history studies are needed to find such variables. The present study investigated
      whether the same behavioural problem dimensions (internalizing, externalizing,
      attention) found among children and adolescents with behaviour management
      problems and/or dental fear could also be found among severely fearful adult
      patients. METHODS: The participants were 230 consecutive adult patients applying
      for treatment for severe dental anxiety at a specialized clinic. Patients
      completed a version of the Rutter behaviour questionnaire that was adapted for
      adults. Comparison data were the Hospital Anxiety and Depression scale and self
      rated anger evoked by dental fear. Background data, including dental fear, were
      also collected. Descriptive statistics, principal components analyses, group
      comparisons and correlations were calculated. RESULTS: Of the three behaviour
      problems scales we adapted for adults, two (Internalizing and Attention) had
      acceptable psychometric properties and meaningful relations with the comparison
      variables. In contrast, the third problem scale (Externalizing) proved to have
      less satisfactory properties and relations, especially for men. Patients with
      severe phobia had higher levels of problem behaviours than patients with less
      severe phobia. CONCLUSIONS: Internalizing and Attention scales for adults seem
      promising for use in future prospective studies of the natural history of dental
      fear. The Externalizing scale, however, needs to be studied with a wider range of
      comparison variables and measures of social desirability.

PMID- 17518966
TI  - The independent contribution of neighborhood disadvantage and individual-level
      socioeconomic position to self-reported oral health: a multilevel analysis.
AB  - OBJECTIVES: To examine the association between neighborhood disadvantage and
      individual-level socioeconomic position (SEP) and self-reported oral health.
      METHODS: A population-based cross-sectional study conducted in 2003 among males
      and females aged 43-57 years. The sample comprised 2915 individuals and 60
      neighborhoods and was selected using a stratified two-stage cluster design. Data
      were collected using a mail survey (69.4% response rate). Neighborhood
      disadvantage was measured using a census-based composite index, and individual
      level SEP was measured using education and household income. Oral health was
      indicated by self-reports of the impact of oral conditions on quality of life (0
      = none or minor, 1 = severe), self-rated oral health (0 = excellent-good, 1 =
      fair/poor) and missing teeth (measured as a quantitative outcome). Data were
      analyzed using multilevel modeling. RESULTS: After adjusting for age, sex,
      education, and household income, residents of socioeconomically disadvantaged
      neighborhoods were significantly more likely than those in more advantaged
      neighborhoods to indicate negative impacts of oral conditions on quality of life,
      to assess their oral health as fair or poor, and to report greater tooth loss. In
      addition, respondents with low levels of education and those from a low income
      household reported poorer oral health for each outcome independent of
      neighborhood disadvantage. CONCLUSIONS: The socioeconomic characteristics of
      neighborhoods are important for oral health over and above the socioeconomic
      characteristics of the people living in those neighborhoods. Policies and
      interventions to improve population oral health should be directed at the social,
      physical and infrastructural characteristics of places as well as individuals
      (i.e. the traditional target of intervention efforts).

PMID- 17518967
TI  - Effectiveness of ART and traditional amalgam approach in restoring single-surface
      cavities in posterior teeth of permanent dentitions in school children after 6.3
      years.
AB  - OBJECTIVES: The Atraumatic Restorative Treatment (ART) approach was compared with
      the traditional amalgam (TA) approach in order to test their appropriateness to
      complement a preventive and educational school oral health programme in Syria.
      METHODS: Using a parallel group design, 370 and 311 grade 2 children were
      randomly assigned to the ART and the TA group respectively. Eight dentists placed
      1117 single- and multiple-surface restorations. A modified actuarial method was
      used to estimate survival curves. The jackknife method was applied to calculate
      the standard error in the cumulative survival percentages. RESULTS: A
      statistically significant difference in cumulative survival percentages between
      single-surface non-occlusal ART and comparable amalgam restorations was observed
      after 4.3, 5.3 and 6.3 years. The survival of single-surface non-occlusal ART
      posterior restorations (80.2 +/- 4.9%) was statistically significantly higher
      than that of occlusal posterior ART restorations (64.8 +/- 3.9%) at evaluation
      year 6.3. There was no statistically significant difference observed between
      survival percentages of large (55.8 +/- 10%) and that of small (69.2 +/- 4.6%)
      single-surface posterior ART restorations after 6.3 years. There was an operator
      effect observed for single-surface ART and comparable amalgam restorations.
      Secondary caries was observed in 2.3% of single-surface ART restorations and in
      3.7% of single-surface amalgam restorations during the 6.3 year observation
      period. CONCLUSIONS: The ART approach provided higher survival percentages for
      single-surface restorations than the TA approach over 6.3 years and is therefore
      appropriate for use in school oral health programmes. Secondary caries was only a
      minor reason for ART restorations to fail. An operator effect was observed for
      both treatment approaches.

PMID- 17518968
TI  - A randomized trial of the effectiveness of home visits in preventing early
      childhood caries.
AB  - OBJECTIVES: Assess the effectiveness of home visits for advising mothers about
      breast feeding and weaning on early childhood caries (ECC) at the age of 12
      months. METHODS: A randomized field trial was conducted in mothers who gave birth
      within the public health system in the Brazilian city of Sao Leopoldo
      (intervention group = 200; controls = 300). The intervention group received the
      advice 10 days after the child's birth, monthly up to 6 months, at 8, 10 and 12
      months, based on the 'Ten Steps for Healthy Feeding', a Brazilian national health
      policy for primary care, based on WHO guidelines. Both groups had research
      assessment at 6 and 12 months, with dental caries investigated in this last
      assessment; 122 children were lost in the 1-year follow-up; 378 were assessed for
      caries: two predentulous children were excluded from the analysis. Mann-Whitney U
      was used to test if the average number of decayed surfaces (DS; white spots and
      cavities) differed between the intervention and control groups, and logistic
      regression to estimate the effects of the intervention on the odds of ECC. Chi
      square test was used to test for differences between the intervention and control
      groups in the distribution of feeding behaviours tackled by the dietary
      intervention. RESULTS: 10.2% of the children in the intervention group and 18.3%
      of the controls had caries. The odds of caries was 48% lower for the intervention
      group, adjusted for number of teeth (OR = 0.52, 95% CI = 0.27-0.97). Mean DS were
      lower for the intervention group (0.37) when compared with the control group
      (0.63), (Mann-Whitney U, P = 0.03). The intervention group had significantly
      longer duration of exclusive breast feeding (P = 0.000), later introduction of
      sugar (P = 0.005), and smaller probability of ever having eaten biscuits (P =
      0.000), honey (P = 0.003), soft drinks (P = 0.02), fromage-frais (P = 0.001),
      chocolate and sweets (P = 0.001). CONCLUSIONS: ECC is a public health problem in
      that population. The home visits for dietary advice appear to help reducing
      dental caries in infants. Greater efforts are needed to tackle cariogenic dietary
      behaviours even further, as a relevant proportion of children of the intervention
      group were shown to present with dental caries. Further studies should examine
      the effect of the intervention in the longer term.

PMID- 17518969
TI  - Correlates of partial tooth loss and edentulism in the Brazilian elderly.
AB  - BACKGROUND: In South American older adults the association between tooth loss and
      demographic, predisposing and enabling factors has not been determined. The
      purpose of this study was to evaluate the association between partial and
      complete tooth loss and demographic, predisposing, enabling and need factors, and
      quality of life variables in the Brazilian older adults. METHODS: In this cross
      sectional study, 5349 subjects aged 65-74 years were evaluated using conglomerate
      random sampling. Data collection included dental examinations and questionnaires
      evaluating demographic, predisposing, enabling and need factors, and quality of
      life variables. Multinomial logistic regression was carried out to evaluate
      correlates of tooth loss. The number of teeth was set as the outcome and
      categorized as: edentulous, subjects with 1-19 teeth, and subjects with 20 or
      more teeth. RESULTS: Predisposing factors including age, female gender and
      schooling were independently associated with edentulism. Female gender was
      associated with partial tooth loss. The only enabling factor associated with
      edentulism was car ownership. Need factors were associated with edentulism and
      partial tooth loss. Edentulous subjects perceived the need for dental treatment
      less frequently. Quality of life factors were associated with partial tooth loss
      and edentulism. Subjects with 1-19 teeth and edentulous subjects were more likely
      to rate their chewing ability as not good. Edentulous subjects were more likely
      to rate their speech ability and their dental appearance as good. CONCLUSIONS:
      The results indicate that tooth loss and edentulism were complex phenomena, with
      intricate predisposing, demographic, enabling and need factors playing a role.

PMID- 17518970
TI  - Racial disparity in stage at diagnosis and survival among adults with oral cancer
      in the US.
AB  - OBJECTIVES: To explore distribution of stage at diagnosis and relative survival
      rates among US adults with oral cavity cancer in relation to race, and over time.
      METHODS: We obtained 1973-2002 oral cancer incidence data from the Surveillance,
      Epidemiology, and End Results (SEER) Program, and computed proportions for each
      oral cavity site by stage at diagnosis, tumor size, and 5-year relative survival
      rates among Whites and Blacks. RESULTS: A total of 46 855 cases of oral cavity
      cancer were reported to the SEER registry among adults > or =20 years between
      1973 and 2002. African-Americans had a significantly higher proportion of cancer,
      mainly in the tongue, that had spread to a regional node or to a distant site at
      diagnosis than Whites: 67% versus 49% of tongue cancers reported from 1973 to
      1987 (P < 0.001), and 70% versus 53% of those reported from 1988 to 2002 (P <
      0.001). They had a significantly higher proportion of tongue cancer that were >4
      cm in diameter at time of diagnosis (59% versus 44%; P < 0.001), and black men in
      particular experienced lower 5-year relative survival rates than white men, in
      particular, for tongue cancer (25% versus 43% from 1973 to 1987, and 31% versus
      53% from 1988 to 2002). CONCLUSION: There are significant racial disparities with
      respect to stage at diagnosis and survival among adults with oral cancer reported
      to the SEER registry from 1973 to 2002. One possible explanation for the lower
      survival among Blacks may be a difference in access to, and utilization of,
      healthcare services.

PMID- 17518971
TI  - Regulation of the muscle-specific AMP-activated protein kinase alpha2beta2gamma3
      complexes by AMP and implications of the mutations in the gamma3-subunit for the
      AMP dependence of the enzyme.
AB  - The AMP-activated protein kinase is an evolutionarily conserved heterotrimer that
      is important for metabolic sensing in all eukaryotes. The muscle-specific isoform
      of the regulatory gamma-subunit of the kinase, AMP-activated protein kinase
      gamma3, has a key role in glucose and fat metabolism in skeletal muscle, as
      suggested by metabolic characterization of humans, pigs and mice harboring
      substitutions in the AMP-binding Bateman domains of gamma3. We demonstrate that
      AMP-activated protein kinase alpha2beta2gamma3 trimers are allosterically
      activated approximately three-fold by AMP with a half-maximal stimulation
      (A(0.5)) at 1.9 +/- 0.5 or 2.6 +/- 0.3 microm, as measured for complexes
      expressed in Escherichia coli or mammalian cells, respectively. We show that
      mutations in the N-terminal Bateman domain of gamma3 (R225Q, H306R and R307G)
      increased the A(0.5) values for AMP, whereas the fold activation of the enzyme by
      200 microm AMP remained unchanged in comparison to the wild-type complex. The
      mutations in the C-terminal Bateman domain of gamma3 (H453R and R454G), on the
      other hand, substantially reduced the fold stimulation of the complex by 200
      microm AMP, and resulted in AMP dependence curves similar to those of the double
      mutant, R225Q/R454G. A V224I mutation in gamma3, known to result in a reduced
      glycogen content in pigs, did not affect the fold activation or the A(0.5) values
      for AMP. Importantly, we did not detect any increase in phosphorylation of Thr172
      of alpha2 by the upstream kinases in the presence of increasing concentrations of
      AMP. Taken together, the data show that different mutations in gamma3 exert
      different effects on the allosteric regulation of the alpha2beta2gamma3 complex
      by AMP, whereas we find no evidence for their role in regulating the level of
      phosphorylation of alpha2 by upstream kinases.

PMID- 17518972
TI  - Cloning of type 1 cannabinoid receptor in Rana esculenta reveals differences
      between genomic sequence and cDNA.
AB  - The endocannabinoid system is a conserved system involved in the modulation of
      several physiologic processes, from the activity of the central nervous system to
      reproduction. Type 1 cannabinoid receptor (CNR1) cDNA was cloned from the brain
      and testis of the anuran amphibian, the frog Rana esculenta. Nucleotide identity
      ranging from 62.6% to 81.9% is observed among vertebrates. The reading frame
      encoded a protein of 462 amino acids (FCNR1) with all the properties of a
      membrane G-coupled receptor. Alignments of FCNR1 with those of other vertebrates
      revealed amino acid identity ranging from 61.9% to 88.1%; critical domains for
      CNR1 functionality were conserved in the frog. As nucleotide differences of cnr1
      cDNA were observed in brain and testis, the genomic sequence of the cnr1 gene was
      also determined in the same tissue preparations. Nucleotide changes in codons 5,
      30, 70, 186, 252 and 408 were observed when cDNA and genomic DNA were compared;
      the nucleotide differences did not affect the predicted amino acid sequences,
      except for changes in codons 70 and 408. Interestingly, the predicted RNA folding
      was strongly affected by different nucleotide sequences. Comparison of cnr1 mRNA
      sequences available in GenBank with the corresponding genomic sequences revealed
      that also in human, rat, zebrafish and pufferfish, nucleotide changes between
      mRNA and genomic sequences occurred. Furthermore, amino acid sequences deduced
      from both mRNA and the genome were compared among vertebrates, and also in
      pufferfish the nucleotide changes corresponded to modifications in the amino acid
      sequence. The present results indicate for the first time that changes in
      nucleotides may occur in cnr1 mRNA maturation and that this phenomenon might not
      be restricted to the frog.

PMID- 17518973
TI  - Quality of reporting masticatory muscle electromyography in 2004: a systematic
      review.
AB  - This study evaluated the quality of reporting electromyography in studies
      evaluating the masticatory muscles published during 2004. Several electronic
      databases were searched. Abstracts and later articles were selected by a
      consensus from the five reviewers. An adaptation of the methodological checklist
      published by the International Society of Electrophysiology and Kinesiology
      (ISEK) was used. The following information regarding electrodes was reported on
      the 35 finally selected articles: location (94.3%), interelectrode distance
      (48.6%), and material (42.9%); detection and amplification: amplification type
      (54.3%), gain (25.7%), low high pass filters (60%) and cut-off frequencies (60%);
      electromyography (EMG) processing: sampling rate (74.2%), rectification (46.6%),
      root-mean square (RMS) (39.2%); number of bits and model of A/D card (17.1%); and
      normalization procedure (40%). Reasons for the poor reporting are discussed.
      Because of the general poor quality of reporting of the analysed studies,
      findings of studies using surface electromyography of masticatory muscles should
      be interpreted with caution.

PMID- 17518974
TI  - The lateral leeway in the habitual intercuspation: experimental studies and
      literature review.
AB  - The habitual intercuspation is used ubiquitous for manufacturing small dental
      restorations. However, a little is known on its precision. The aim of the present
      study was therefore to investigate the unambiguity and accuracy of the habitual
      occlusion in mounted plaster casts from fully dentate persons. Eighty-one fully
      dentate volunteers, 36 women and 45 men aged 26.8 +/- 6.2 years (18-55 years),
      with minor fillings and no signs or symptoms of TMD took part in the experiments.
      Silicone impressions were taken, poured with stone plaster and the obtained casts
      mounted into Dentatus ARL(R)- articulators using an individual face bow transfer.
      Subsequently, the models were transferred to a custom-made measuring articulator
      where the lateral leeway and the accuracy of the hand-held habitual
      intercuspation were quantified in the condylar area. Measurements were repeated
      seven times with the upper cast pushed either to the maximum right or the maximum
      left intercuspation. The hand-held habitual intercuspation of upper and lower
      cast proved ambiguous in 57% of pairs of casts. The average lateral leeway of the
      habitual intercuspation in the condylar area was 0.10 +/- 0.05 mm (0-0.51 mm;
      median 0.07 mm) between the maximum right and left occlusal positions. The
      average accuracy of three repeated measurements was 0.22 +/- 0.09 mm (0.02-1.17
      mm; median 0.16 mm). Natural occlusal surfaces in a full dentition do not
      guarantee an unambiguous habitual intercuspation of the plaster casts. The
      described leeway and technical limits might be possible causes for occlusal
      adjustments that are sometimes necessary when inserting restorations manufactured
      in habitual intercuspation.

PMID- 17518975
TI  - Influences of body posture on duration of oral swallowing in normal young adults.
AB  - The primary purpose of this study was to determine whether body posture altered
      the duration of oral swallowing. To answer this question, we recorded
      electromyograms (EMGs) from the anterior tongue and suprahyoid (SH) muscles as
      well as laryngeal movement associated with swallowing in nine normal young
      subjects. The subjects swallowed a test food after receiving a signal while in
      four randomly set postures: upright, two inclined (60 degrees and 30 degrees to
      the horizontal), and supine positions. We measured the durations from the start
      to the peak and from the peak to the end of the integrated tongue and SH EMGs. We
      assumed that the duration from the start to the peak of the integrated SH EMG
      would correspond to the duration of oral swallowing. The average duration from
      the start to the peak of the integrated SH EMG decreased after moving from the
      upright to the inclined and supine positions. The decrease in the duration was
      statistically significant and consistent for three experimental sessions. The
      duration from the start to the peak of the integrated tongue EMG during
      swallowing tended to decrease after lying down, but not significantly. The
      postural changes did not affect the remaining four durations. The decrease in the
      duration of oral swallowing induced by lying down suggests that the gravitational
      force placed on the test food facilitates the swallowing reflex. Large variation
      in the tongue activity during swallowing among the subjects can probably be
      attributed to the lack of a significant decrease in the duration of the tongue
      activity.

PMID- 17518976
TI  - Evaluation of chewing and swallowing disorders among frail community-dwelling
      elderly individuals.
AB  - The purpose of the present study was to develop a new assessment scale to
      evaluate the risk of chewing and swallowing disorders among frail community
      dwelling elderly individuals. Subjects were 85 frail elderly individuals (29 men
      and 56 women) living in southern Japan. First, we pooled 18 subjectively
      evaluated variables identified by previous studies as being related to chewing
      and swallowing disorders. Secondly, using factor analysis, we extracted 12
      variables as the 'dysphagia risk assessment for the community-dwelling elderly'
      (DRACE) and examined its reliability using Cronbach's alpha coefficient. Thirdly,
      we examined the validity of the DRACE by comparing it with an existing method for
      evaluating dysphagia. Cronbach's alpha coefficient of the DRACE was 0.88,
      indicating satisfactory reliability. Dysphagia risk assessment for the community
      dwelling elderly scores were significantly related to the results of the 3-oz
      water test (P < 0.01). Furthermore, DRACE scores were closely associated with
      activities of daily living as evaluated by the Barthel index, a tendency that was
      consistent with previous studies. These findings suggest that the DRACE is a
      useful tool with sufficient reliability and validity to detect latent risk of
      chewing and swallowing disorders among frail community-dwelling elderly
      individuals.

PMID- 17518977
TI  - Relationship between number of natural teeth in older Japanese people and health
      related functioning.
AB  - The objective was to assess the relationship between number of functional
      occluding natural pairs of teeth and health related functioning in older free
      living Japanese people using the SF-20. The participants were 107 elderly people
      aged 80 years. Health related functioning was measured with the SF-20. The
      numbers of functional occluding natural pairs of teeth (OPs) were calculated and
      scored as follows: 1, for each pair of anterior teeth and premolars in occlusion.
      Molar functional natural occluding pairs were scored 2 for each occluding pair.
      The number of functional occluding pairs was assessed separately as anterior
      natural occluding pairs (AOPs) and posterior occluding pairs (POPs). There were
      significant differences in the role functioning subscale of SF-20 between those
      who were edentulous and those with one to nine natural teeth and 10 or more
      natural teeth (P = 0.030). Those with one to six AOPs had significantly higher
      role functioning than the zero AOPs group (P = 0.042). Those with 1-12 POPs also
      had significantly higher role functioning scores than the zero natural POPs group
      (P = 0.007). However, there were no significant relationships between number of
      natural teeth, OPs or AOPs, and POPs on the one hand, and all other subscales of
      SF-20 on the other hand. The community-dwelling 80-year-old Japanese people in
      this study had overall good health related functioning. The number of functional
      occluding pairs of natural teeth, especially POPs, was related with the role
      functioning subscale of SF-20 but had no significant relationships to the other
      dimensions of SF-20.

PMID- 17518978
TI  - Establishing a reliable protocol to measure tongue sensation.
AB  - The relationship between tongue sensation and tongue function for speech,
      mastication and deglutition are growing areas of interest among rehabilitative
      professionals. To determine the potential effect that sensation has on function,
      it is imperative that, first, reliable and valid measures of tongue sensation be
      established. The aim of this study was to develop a protocol to test tongue
      sensation across a spectrum of sensory functions that included two-point
      discrimination, light-touch discrimination, thermal sensation, texture
      recognition, oral stereognosis and taste recognition. Materials tested within
      each domain respectively included: (i) the MacKinnon-Dellon Disk-criminator,
      paperclip and caliper; (ii) the Semmes-Weinstein monofilament and cotton wisp;
      (iii) dental mirrors and glass test tubes; (iv) spheres of textured acrylic resin
      on rods; (v) acrylic resin forms with differing shapes on rods and (vi) salty,
      sweet, sour, bitter and neutral solutions. Materials were tested on 40 healthy
      subjects between the ages of 20 and 55. The results from this study indicated
      that thermal, texture and taste sensations appear robust for accuracy and
      discrimination. Two-point discrimination and light touch seem to be influenced by
      location of stimulation on the tongue and force applied, whereas stereognosis was
      influenced by stimulus complexity. The results of this study indicate that
      clinicians may choose instruments as practical as paperclips and test tubes for
      testing two-point discrimination and thermal sensation, respectively. For the
      other sensations, it may be important to use more sophisticated instrumentation
      to control variables of force, surface area stimulated and assessing sensations
      in graded steps.

PMID- 17518979
TI  - New method for evaluation of tongue-coating status.
AB  - The purpose of this study was to determine the viability of Tongue Coating Index,
      which is a new method for evaluating tongue-coating status. To determine the
      reliability and reproducibility of our new evaluation criteria (Score 0: Tongue
      coating not visible; Score 1: Tongue coating thin, papillae of tongue visible;
      Score 2: Tongue coating very thick, papillae of tongue not visible), 10 observers
      evaluated 20 photographs of tongues. Each tongue surface was divided into nine
      sections. Observers evaluated each section according to our new criteria and each
      score for tongue-coating status was recorded in the pertinent section of the
      Tongue Coating Record form. They repeated the same evaluation 2 weeks after the
      first evaluation. The relationship between the scores obtained and number of oral
      microorganisms was investigated in 50 edentulous patients. Tongue coating was
      collected from the tongue surface after evaluation of tongue-coating status. The
      total number of anaerobic bacteria and the number of Candida species were counted
      from the specimens collected. Interobserver agreement and intraobserver agreement
      were 0.66 and 0.80 by Cohen's kappa, respectively. No significant difference was
      observed in the number of Candida species among the three scores. The number of
      total anaerobic bacteria, however, was significantly different among the scores
      (P < 0.05). Therefore, we conclude that our method for evaluating tongue-coating
      status offers new criteria that are superior in reliability and reproducibility,
      and that also reflect the total number of anaerobic bacteria present on the
      dorsum of the tongue.

PMID- 17518980
TI  - Denture-related stomatitis: identification of aetiological and predisposing
      factors - a large cohort.
AB  - The aim of this study was to identify and characterize aetiological and
      predisposing factors in denture-related stomatitis (DRS), by means of a case
      control, transversal study, in a large cohort of 140 persons wearing removable
      maxillary polymethylamethacrylate prostheses. Data were obtained by (1) a
      questionnaire that included the identification of the subject, demographic and
      social data, medical history and behaviour; (2) intra-oral examination; (3)
      evaluation of the prosthesis; (4) microbiological examination; (5) yeast
      identification and analyses using Epi-info and the chi-square test. Results
      showed significant associations between DRS and yeasts, gender, age and alcohol
      consumption. We also found a significant relationship between the presence of
      yeasts and hyposalivation and decreased salivary pH. We found a highly
      significant difference between groups with and without DRS concerning the
      presence or absence of yeasts, regardless of the sample origin. Most cases of DRS
      showed the presence of Candida albicans. The results confirm a highly significant
      difference between groups with and without DRS concerning the presence or absence
      of yeasts.

PMID- 17518981
TI  - Panoramic findings in 34-year-old subjects with facial pain and pain-free
      controls.
AB  - The aim of this study was to compare panoramic radiographic findings between
      subjects with reported facial pain and pain-free controls in a population-based
      sample of 34-year olds. The study was a part of a comprehensive medical survey
      including subjects born in the year 1966 in Northern Finland. A sub-sample of the
      cohort was formed based on the question concerning facial pain. A panoramic
      radiograph was taken of 48 subjects with facial pain and 47 pain-free controls.
      Pathological findings in the dentition, jaws, maxillary sinuses and
      temporomandibular joints (TMJs) were compared between the groups. The majority of
      the subjects in both groups did not have pathological findings. Compared with
      controls, the subjects with facial pain did not show significantly more
      pathological findings in the teeth, periodontium, maxillary sinuses, TMJs or in
      the other areas. Radiographic panoramic findings had no association with reported
      facial pain in the population-based sample of young adults, and have little
      impact on the diagnosis of facial pain.

PMID- 17518982
TI  - Influence of the shape core on custom cast dowel and core removal by ultrasonic
      energy.
AB  - The aim of this study was to assess the influence of the shape of custom cast
      dowel and cores on their removal by the use of ultrasound technique. Twenty-four
      single-rooted bovine teeth were prepared and had cast dowel fixed with zinc
      phosphate cement. The teeth were randomly divided into two groups: group I-
      received custom cast dowel and cores made without the coronal portion anatomy,
      simulating removal this portion with a bur, and group II- received cores that
      reproduced the coronal anatomy. Both were treated with an ultrasound device in
      two three-minute cycles (US). The force necessary for dowel removal was
      determined using a mechanical test machine. In the second stage of the study, the
      custom cast dowel and cores were again cemented and no ultrasound vibration was
      used on them (C). Data were submitted to the two-way anova (2 x 2) and Tukey test
      (P < 0.05), resulting in decreased tensile strength values (Kgf): GIC (49.85 +/-
      11.10); GIIC (48.22 +/- 11.09); GIIUS (32.36 +/- 6.21) and GIUS (8.0 +/- 7.52).
      It was concluded that the shape of the core without the anatomic coronal portion
      facilitated removal of intra-radicular retention only when associated with the
      use of ultrasound.

PMID- 17518983
TI  - The effect of two root canal sealers on the retentive strength of glass fibre
      endodontic posts.
AB  - This study was undertaken to examine the effect of eugenol-containing and non
      eugenol-containing root canal sealers on the retention strength of glass fibre
      endodontic posts (ParaPost Fibre White) luted with a resin cement (ParaPost
      cement). We also examined the mode of failure that occurred visually by using
      scanning electron microscopy. Seventy-two single rooted, recently extracted,
      premolar teeth were root canal treated and randomly divided into two groups.
      Group 1 was obturated with gutta percha and a calcium hydroxide-based sealer
      (Sealapex, Kerr). Group 2 was obturated with gutta percha and a eugenol-based
      sealer (Tubli-Seal Kerr). The teeth were stored for 1 week in distilled water at
      37 degrees C and then prepared for 9 mm posts with a 1.40-mm drill. The matching
      glass fibre post was luted with a resin cement following the manufacturer's
      instructions. The samples were stored for 1 week and thermocycled. The posts were
      removed from the root canals using a calibrated testing machine in tensile mode.
      The mean dislodging force for group 1 was 190.46 N and for group 2 was 183.8 N,
      with standard deviations of 54.9 and 56.0 N respectively. The t-test indicated no
      significant difference between the two groups. Failure of the posts occurred
      mainly within the resin layer. This study showed that under experimental
      conditions there was no statistically significant difference between Sealapex
      sealer and Tubli-Seal sealer on the retention of glass fibre posts using a resin
      cement.

PMID- 17518985
TI  - Anchorless keratinocyte survival: an emerging pathogenic mechanism for squamous
      cell carcinoma in recessive dystrophic epidermolysis bullosa.
AB  - Squamous cell carcinomas in patients suffering from recessive dystrophic
      epidermolysis bullosa are highly invasive and frequently metastatic. Expression
      of a collagen VII fragment (NC1) has been described as a prerequisite for the
      development of this tumor form. This commentary focuses on potential molecular
      mechanisms by which expression of the NC1 fragment may augment anchorage
      independent growth and survival of malignant keratinocytes.

PMID- 17518986
TI  - Plakoglobin-dependent disruption of the desmosomal plaque in pemphigus vulgaris.
AB  - We recently reported that the pathogenesis of pemphigus vulgaris (PV), an
      autoimmune blistering skin disorder, is driven by the accumulation of c-Myc
      secondary to abrogation of plakoglobin (PG)-mediated transcriptional c-Myc
      suppression. PG knock-out mouse keratinocytes express high levels of c-Myc and
      resemble PVIgG-treated wild-type keratinocytes in most respects. However, they
      fail to accumulate nuclear c-Myc and loose intercellular adhesion in response to
      PVIgG-treatment like wild-type keratinocytes. This suggested that PG is also
      required for propagation of the PVIgG-induced events between augmented c-Myc
      expression and acantholysis. Here, we addressed this possibility by comparing
      PVIgG-induced changes in the desmosomal organization between wild-type and PG
      knock-out keratinocytes. We found that either bivalent PVIgG or monovalent PV-Fab
      (known to trigger blister formation in vivo) disrupt the linear organization of
      all major desmosomal components along cell borders in wild-type keratinocytes,
      simultaneously with a reduction in intercellular adhesive strength. In contrast,
      PV-Fab failed to affect PG knock-out keratinocytes while PVIgG cross-linked their
      desmosomal cadherins without significantly affecting desmoplakin. These results
      identify PG as a principle effector of the PVIgG-induced signals downstream of c
      Myc that disrupt the desmosomal plaque at the plasma membrane.

PMID- 17518987
TI  - Differential p53-mediated responses to solar-simulated radiation in human
      papillomavirus type 16-infected keratinocytes.
AB  - In immunocompromised patients, cooperative effects of human papillomavirus (HPV)
      and ultraviolet (UV) radiation have been postulated in the development of non
      melanoma skin cancers. The tumor suppressor p53 is a key component of the
      cellular response to genotoxic agents, such as UV radiation. We have previously
      demonstrated that in HPV16-infected cells, a higher E6* level was associated with
      a higher resistance to UV and oxidative stress. Using the two same SKv cell
      lines, the aim of the present study was to investigate p53 and p21 expression and
      cell death in HPV-infected keratinocytes in response to UV irradiation and to
      determine the role of HPV oncoprotein levels on the p53-mediated cellular
      response. We demonstrated that the weakly E6*-expressing level SKv-e cell line
      presented both higher cytotoxicity and apoptosis to UV. This high sensitivity was
      associated with both p53 and p21 nuclear accumulation, while a high E6* level and
      resistance were associated with no p53 accumulation and a p21 nuclear down
      regulation after UV. Moreover, in SKv-e cell line, p21 promoter activation was
      p53 dependent. Our results suggest that an alteration and/or a modulation of the
      p53-p21 pathway in response to UV could be determinant for HPV-infected
      keratinocyte survival and HPV-associated carcinogenic process.

PMID- 17518988
TI  - Squamous cell carcinoma induced by ultraviolet radiation originates from cells of
      the hair follicle in mice.
AB  - Short-wave ultraviolet radiation (UVB) is the most carcinogenic part of the
      ultraviolet spectrum. The target cells of skin cancer are believed to be the
      bulge stem cells and/or their offspring, the transit-amplifying cells that reside
      in the epidermis. However, the amount of UVB penetrating epidermis and reaching
      the bulge cells is very low, which questions if these cells suffer sufficient DNA
      damage to transform into cancer stem cells. We performed this study to determine
      whether UV-induced squamous cell carcinoma (SCC) originates from the epidermis or
      the hair follicles in mice. Hairless mice had their epidermis removed at
      different levels using CO(2) laser ablation. Simulated solar irradiations were
      administered either preoperatively (in total 7 weeks) or pre- and postoperatively
      (in total 30 weeks). Control groups were untreated or treated only with solar
      simulated radiation or with laser. Blinded clinical assessments of skin tumors
      were carried out weekly during 12 months observation. Only mice irradiated with
      solar-simulated radiation both pre- and postoperatively developed tumors. Median
      time to first, second and third tumor ranged from 19 to 20.5 weeks and was not
      significantly different between the non-laser and laser-treated groups (P >
      0.05). The tumor response was thus similar in UV-exposed mice whether they had
      their epidermis removed or not. No tumors appeared in control groups. Hence, UV
      induced SCC of mice originates from cells of the hair follicle, presumably the
      bulge stem cells, indicating that ultraviolet radiation penetrates epidermis
      sufficiently to cause irreversible DNA damage in cells located beneath the
      epidermis.

PMID- 17518989
TI  - A topical lipophilic niacin derivative increases NAD, epidermal differentiation
      and barrier function in photodamaged skin.
AB  - The effects of myristyl nicotinate (MN), a nicotinic acid derivative designed to
      deliver nicotinic acid to skin without vasodilatation, on subjects with
      photodamaged skin have been studied. MN increased skin cell nicotinamide adenine
      dinucleotide (NAD) by 25% (P = 0.001) demonstrating effective delivery of
      nicotinic acid to skin. Relative to placebo, MN treatment of photodamaged facial
      skin increased stratum corneum thickness by approximately 70% (P = 0.0001) and
      increased epidermal thickness by approximately 20% (P = 0.001). In two separate
      studies, MN treatment increased rates of epidermal renewal by 6% (P = 0.003) to
      11% (P = 0.001) and increased the minimal erythemal dose by 8.9 (P = 0.07) and
      10% (P = 0.05) relative to placebo. MN treatment resulted in reductions in the
      rates of transepidermal water loss (TEWL) of approximately 20% relative to
      placebo on cheeks (P = 0.012) and arms (P = 0.017) of study subjects. Results of
      a tape stripping challenge before and after MN treatment demonstrated a
      significant correlation (P = 0.03) between increased skin NAD content and
      resistance to changes in TEWL for MN treated but not placebo subjects. Rates of
      TEWL changed more rapidly and to a greater extent in atopic subjects compared
      with normal subjects. The results indicate that MN enhances epidermal
      differentiation and barrier function in skin, suggesting that this method of
      nicotinic acid delivery may prove useful in limiting progression of actinic skin
      damage and possibly in treating other conditions involving skin barrier
      impairment.

PMID- 17518990
TI  - In vitro modulation of TLR-2, CD1d and IL-10 by adapalene on normal human skin
      and acne inflammatory lesions.
AB  - The anti-inflammatory mechanisms of adapalene, a synthetic retinoid used for the
      treatment of acne patients, are partially understood. They seem particularly
      related to the modulation of the non-specific immunity. Recent studies have shown
      that Toll-like receptor (TLR)-2 expression, a receptor of the innate immune
      system, was increased in acne lesions and could play an essential role in acne
      linked inflammation. The aim of our study was to investigate the new mechanisms
      of the anti-inflammatory activity of adapalene in vitro, and more specifically
      the modulatory effect of adapalene on the expression of TLR-2, CD1d, a cell
      surface glycoprotein that plays a role as antigen-presenting molecules and is
      responsible for the development of cutaneous inflammation, and also on the
      expression and the secretion of the anti-inflammatory interleukin (IL)-10
      cytokine. Both explants of normal human skin and explants of acne patients were
      incubated with adapalene (10(-7) or 10(-6) M) or the control medium for 24 h.
      Evaluation of epidermal expression by immunohistochemistry showed a decreased
      expression of TLR-2 and IL-10 in explants of normal skin and explants of acne
      with adapalene. On the contrary, adapalene increased CD1d expression in explants
      of acne patients. Thus, adapalene can modulate the epidermal immune system by
      increasing the CD1d expression and by decreasing the IL-10 expression by
      keratinocytes. Moreover, these modulations could increase the interactions
      between dendritic cells and T lymphocytes and could strengthen the antimicrobial
      activity against Propionibacterium acnes. The decreased expression of TLR-2 by
      the keratinocytes can contribute to explain the anti-inflammatory activity of
      adapalene observed in clinical practice.

PMID- 17518992
TI  - Human tissue kallikrein expression in the stratum corneum and serum of atopic
      dermatitis patients.
AB  - Human tissue kallikreins are a family of 15 trypsin- or chymotrypsin-like
      secreted serine proteases (KLK1-KLK15). Many KLKs have been identified in normal
      stratum corneum (SC) and sweat, and are candidate desquamation-related proteases.
      We report quantification by enzyme-linked immunosorbent assay (ELISA) of KLK5,
      KLK6, KLK7, KLK8, KLK10, KLK11, KLK13 and KLK14 in the SC and serum of atopic
      dermatitis (AD) patients by ELISA, and examine their variation with clinical
      phenotype, correlation with blood levels of eosinophils, lactate dehydrogenase
      (LDH) and immunoglobulin E. The overall SC serine protease activities were also
      measured. In the SC of AD, all KLKs, except KLK11, were significantly elevated.
      The elevation of chymotrypsin-like KLK7 was predominant, compared with trypsin
      like KLKs. The SC overall plasmin- and furin-like activities were significantly
      elevated, while trypsin- and chymotrypsin-like activities did not differ
      significantly. In the serum of AD patients, KLK8 was significantly elevated and
      KLK5 and KLK11 were significantly decreased. However, their serum levels were not
      modified by corticosteroid topical agents. The alterations of KLK levels in the
      SC of AD were more pronounced than those in the serum. KLK7 in the serum was
      significantly correlated with eosinophil counts in the blood of AD patients,
      while KLK5, KLK8 and KLK11 were significantly correlated with LDH in the serum.
      In conclusion, we report abnormal kallikrein levels in the SC and the serum of AD
      patients. KLKs might be involved in skin manifestation and/or focal/systemic
      inflammatory reactions in AD. Our data may contribute to a better understanding
      of the pathogenesis of AD.

PMID- 17518991
TI  - Role of prostaglandins on mechanical scratching-induced cutaneous barrier
      disruption in mice.
AB  - The role of prostaglandins (PGs) on mechanical scratching-induced cutaneous
      barrier disruption in mice was investigated by comparing the observed effects of
      arachidonic acid (AA) application. Scratching of the mouse skin with a stainless
      steel wire brush (mechanical scratching) was associated with significant, scratch
      count-dependent elevation of the transepidermal water loss (TEWL) and skin PG
      levels (especially PGD(2) and PGE(2)). Histological evidence of inflammation
      (crusta, acanthosis and neutrophilic infiltration) in the skin also became
      evident 24 h after mechanical scratching. On the other hand, while topical
      application of 0.1% AA to the mouse skin also increased the skin PG levels, but
      did not produce any increase of TEWL or histological evidence of inflammation in
      the skin. Topical application of cyclooxygenase inhibitors (indomethacin,
      piroxicam, aspirin, diclofenac and ketoprofen) decreased the spontaneous recovery
      rates from cutaneous barrier disruption. These results suggest that the elevation
      of cutaneous PG production induced by mechanical scratching is involved in the
      repair of the skin damage caused by the scratching.

PMID- 17518993
TI  - Experimental models of epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is an organ-specific autoimmune disease
      with a well-defined antigen-autoantibody system. Recently, mutually complementary
      ex vivo and animal models were developed for this disease. The blister formation
      of EBA can be reproduced by passively transferring antibodies against type VII
      collagen into mice. In addition, the Fc-dependent interaction of autoantibodies
      with granulocytes resulting in dermal-epidermal separation can be studied using
      patient autoantibodies and leukocytes from healthy donors in cryostat sections of
      normal human skin. Finally, the autoimmune response and the active blistering
      disease are replicated by immunizing mice with autologous type VII collagen. The
      results obtained using these experimental systems provided conclusive evidence
      that EBA is an antibody-mediated autoimmune disease. In addition, these models
      represent powerful new tools for understanding EBA pathophysiology and will
      likely offer unique opportunities to investigate the molecular mechanisms of
      antibody-mediated autoimmune diseases in general. Thus, due to improved disease
      modelling, EBA emerges as an exquisitely instructive model disease to study
      fundamental, biologically and clinically crucial aspects of antibody-mediated
      organ-specific autoimmune diseases that extend well beyond the limits of
      autoimmunity against type VII collagen. The new mechanistic insights gained from
      investigating EBA pathogenesis will facilitate the design of immunomodulatory
      interventions for this and other pathogenetically related organ-specific,
      antibody-dependent autoimmune diseases.

PMID- 17518994
TI  - Lessons learned from DNA repair defective syndromes.
AB  - Genomic instability is the driving force behind cancer development. Human
      syndromes with DNA repair deficiencies comprise unique opportunities to study the
      clinical consequences of faulty genome maintenance leading to premature aging and
      premature cancer development. These syndromes include chromosomal breakage
      syndromes with defects in DNA damage signal transduction and double-strand break
      repair, mismatch repair defective syndromes as well as nucleotide excision repair
      defective syndromes. The same genes that are severely affected in these model
      diseases may harbour more subtle variations in the 'healthy' normal population
      leading to genomic instability, cancer development, and accelerated aging at
      later stages of life. Thus, studying those syndromes and the molecular mechanisms
      behind can significantly contribute to our understanding of (skin) cancerogenesis
      as well as to the development of novel individualized preventive and therapeutic
      anticancer strategies. The establishment of centers of excellence for studying
      rare genetic model diseases may be helpful in this direction.

PMID- 17518996
TI  - Genome-wide identification of specific oligonucleotides using artificial neural
      network and computational genomic analysis.
AB  - BACKGROUND: Genome-wide identification of specific oligonucleotides (oligos) is a
      computationally-intensive task and is a requirement for designing microarray
      probes, primers, and siRNAs. An artificial neural network (ANN) is a machine
      learning technique that can effectively process complex and high noise data.
      Here, ANNs are applied to process the unique subsequence distribution for
      prediction of specific oligos. RESULTS: We present a novel and efficient
      algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify
      specific oligos. We establish the unique marker database for human and rat gene
      index databases using the hash table algorithm. We then create the input vectors,
      via the unique marker database, to train and test the ANN. The trained ANN
      predicted the specific oligos with high efficiency, and these oligos were
      subsequently verified by BLAST. To improve the prediction performance, the ANN
      over-fitting issue was avoided by early stopping with the best observed error and
      a k-fold validation was also applied. The performance of the IAB algorithm was
      about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for
      experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively.
      In addition, the results of polymerase chain reactions showed that the primers
      predicted by the IAB algorithm could specifically amplify the corresponding
      genes. The IAB algorithm has been integrated into a previously published
      comprehensive web server to support microarray analysis and genome-wide iterative
      enrichment analysis, through which users can identify a group of desired genes
      and then discover the specific oligos of these genes. CONCLUSION: The IAB
      algorithm has been developed to construct SpecificDB, a web server that provides
      a specific and valid oligo database of the probe, siRNA, and primer design for
      the human genome. We also demonstrate the ability of the IAB algorithm to predict
      specific oligos through polymerase chain reaction experiments. SpecificDB
      provides comprehensive information and a user-friendly interface.

PMID- 17518997
TI  - Children with pertussis inform the investigation of other pertussis cases among
      contacts.
AB  - BACKGROUND: The number of reported pertussis has increased in the last two
      decades. However, many cases of pertussis may be underreported or not diagnosed.
      The World Health Organization estimates that pertussis causes 200,000-400,000
      deaths each year, most deaths are in infants and in developing countries. Infants
      with pertussis can indicate an undetected source cases in the community. METHODS:
      At a University Hospital in Brazil individuals that had frequent contacts with a
      child with confirmed pertussis (the index case) and had recent history of cough
      were enrolled into the study. Nasopharyngeal swabs were collected from every
      contact that had cough within the last 21 days. Cases confirmation followed the
      guidelines of the Center for Disease Control and Prevention-Atlanta, USA.
      RESULTS: Pertussis diagnosis was confirmed in 51 children, (considered the index
      cases). Among the index cases, 72.5% (37/51) were under 6 months of age; culture
      for Bordetella pertussis was positive in 78.4% (40/51). Pertussis was confirmed
      in 39% (107/276) of the contacts of 51 index cases. Among these contacts
      identified as a pertussis case, 40.2% (43/107) were between 6 months and 111/2
      years of age and 59.8% (64/107) were older than 111/2 years of age. Pertussis was
      confirmed by culture in 11.2% (12/107) of them and by epidemiologic linkage in
      88.8% (95/107). Each index case allowed identifying two new cases of pertussis.
      CONCLUSION: Public health authorities should consider implementing early
      recognition of pertussis index cases and searching for pertussis cases among the
      contacts. Treatment of the cases and prophylaxis of the contacts is fundamental
      to control outbreaks in the community.

PMID- 17518998
TI  - Preliminary study on the effect of parenteral naloxone, alone and in association
      with calcium gluconate, on bone healing in an ovine "drill hole" model system.
AB  - BACKGROUND: Several diseases affect bone healing and physiology. Many drugs that
      are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents
      impair bone healing. Stressful conditions are associated with decreased serum
      osteocalcin concentration. High endorphin levels alter calcium metabolism,
      blocking the membrane channels by which calcium normally enters cells. The
      consequent decrease of intracellular calcium impairs the activities of calcium
      related enzymes. Naloxone is a pure opioid antagonist. Morphine-induced
      osteocalcin inhibition was abolished when osteoblasts were incubated with
      naloxone. Naloxone restored the altered cellular and tissue physiology by
      removing beta-endorphins from specific receptors. However, this is only possible
      if the circulating Ca concentration is adequate. The aim of the present study was
      to evaluate the efficacy of parenteral naloxone administration in inducing fast
      mineralization and callus remodelling in a group of sheep with a standardised
      bone lesion. METHODS: Twenty ewes were randomly assigned to 4 treatment groups.
      Group A acted as control, group B received a solution of calcium gluconate, group
      C a solution of naloxone, and group D a solution of calcium gluconate and
      naloxone. A transverse hole was drilled in the left metacarpus, including both
      cortices, then parenteral treatment was administered intramuscularly, daily for
      four weeks. Healing was evaluated by weekly radiographic examination for eight
      weeks. For quantitative evaluation, the ratio of the radiographic bone density
      between the drill area and the adjacent cortical bone was calculated. After eight
      weeks the sheep were slaughtered and a sample of bone was collected for
      histopathology RESULTS: Group D showed a higher radiographic ratio than the other
      groups. Sheep not treated with naloxone showed a persistently lower ratio in the
      lateral than the medial cortex (P < 0.01). Histopathology of bone samples showed
      more caverns and fewer osteoblasts in group D than in the other groups (P </=
      0.001). CONCLUSION: A low-dose parenteral regimen of naloxone enhances
      mineralization and remodelling of the callus in healing cortical defects in
      sheep, especially if associated with calcium gluconate.

PMID- 17518999
TI  - Can asthma control be improved by understanding the patient's perspective?
AB  - BACKGROUND: Clinical trials show that asthma can be controlled in the majority of
      patients, but poorly controlled asthma still imposes a considerable burden. The
      level of asthma control achieved reflects the behaviour of both healthcare
      professionals and patients. A key challenge for healthcare professionals is to
      help patients to engage in self-management behaviours with optimal adherence to
      appropriate treatment. These issues are particularly relevant in primary care,
      where most asthma is managed. An international panel of experts invited by the
      International Primary Care Respiratory Group considered the evidence and
      discussed the implications for primary care practice. DISCUSSION: Causes of poor
      control: Clinical factors such as exposure to triggers and concomitant rhinitis
      are important but so are patient behavioural factors. Behaviours such as smoking
      and nonadherence may reduce the efficacy of treatment and patients' perceptions
      influence these behaviours. Perceptual barriers to adherence include doubting the
      need for treatment when symptoms are absent and concerns about potential adverse
      effects. Under-treatment may also be related to patients' underestimation of the
      significance of symptoms, and lack of awareness of achievable control.
      IMPLICATIONS: Three key implications for healthcare professionals emerged from
      the debate. First, the need for simple tools to assess asthma control. Two
      approaches considered were the monitoring of biometric markers of control and
      questionnaires to record patient-reported outcomes. Second, to understand the
      reasons for poor control for individual patients, identifying both clinical (e.g.
      rhinitis) and behavioural factors (e.g. smoking and nonadherence to treatment).
      Third was the need to incorporate, within asthma review, an assessment of patient
      perspectives including their goals and aspirations and to elicit their beliefs
      and concerns about asthma and its treatment. This can be used as a basis for
      agreement between the healthcare professional and patient on a predefined target
      regarding asthma control and a treatment plan to achieve this. SUMMARY: Optimum
      review of asthma is essential to improve control. A key priority is the
      development of simple and effective tools for identifying poor control for
      individual patients coupled with a tailored approach to treatment to enable
      patients to set and achieve realistic goals for asthma control.

PMID- 17519000
TI  - Larvicidal effects of a neem (Azadirachta indica) oil formulation on the malaria
      vector Anopheles gambiae.
AB  - BACKGROUND: Larviciding is a key strategy used in many vector control programmes
      around the world. Costs could be reduced if larvicides could be manufactured
      locally. The potential of natural products as larvicides against the main African
      malaria vector, Anopheles gambiae s.s was evaluated. METHODS: To assess the
      larvicidal efficacy of a neem (Azadirachta indica) oil formulation (azadirachtin
      content of 0.03% w/v) on An. gambiae s.s., larvae were exposed as third and
      fourth instars to a normal diet supplemented with the neem oil formulations in
      different concentrations. A control group of larvae was exposed to a corn oil
      formulation in similar concentrations. RESULTS: Neem oil had an LC50 value of 11
      ppm after 8 days, which was nearly five times more toxic than the corn oil
      formulation. Adult emergence was inhibited by 50% at a concentration of 6 ppm.
      Significant reductions on growth indices and pupation, besides prolonged larval
      periods, were observed at neem oil concentrations above 8 ppm. The corn oil
      formulation, in contrast, produced no growth disruption within the tested range
      of concentrations. CONCLUSION: Neem oil has good larvicidal properties for An.
      gambiae s.s. and suppresses successful adult emergence at very low
      concentrations. Considering the wide distribution and availability of this tree
      and its products along the East African coast, this may prove a readily available
      and cheap alternative to conventional larvicides.

PMID- 17519001
TI  - Deletion mutagenesis of large areas in Plasmodium falciparum genes: a comparative
      study.
AB  - BACKGROUND: The increasing emergence of Plasmodium falciparum parasites resistant
      to most of the cost-effective drugs has necessitated the identification of novel
      leads and drug targets. Parasite-specific inserts in enzymes that are essential
      for the differentiation and proliferation of malarial parasites have received
      considerable interest since it distinguishes these proteins from their human
      counterparts. The functions of these inserts, which include mediations of protein
      activities or protein-protein interactions, are being investigated by several
      strategies including deletion mutagenesis. A comparative study of five widely
      used PCR-based mutagenesis methods identified a modified inverse PCR method as
      particularly suitable for the deletion of large areas (>100 bp) in malaria
      parasite genes. METHODS: The restriction enzyme-mediated inverse PCR method
      described here incorporates unique restriction enzyme sites at the 5'-ends of
      inverse tail-to-tail primers. The entire gene-containing vector is amplified
      except the desired region to be deleted and cloned using the unique restriction
      sites to increase ligation efficiency. This method was compared in its efficiency
      to delete a ~400 bp parasite-specific insert in malarial S-adenosylmethionine
      decarboxylase/ornithine decarboxylase (PfAdoMetDC/ODC) to existing PCR-based site
      directed deletion mutagenesis methods including the QuickChange site-directed
      mutagenesis, ExSite, overlapping primer and inverse PCR. In addition, the
      modified method was applied in the deletion of a >600 bp parasite-specific insert
      in another malarial gene, pyridoxal kinase (PfPdxK). RESULTS: The modified and
      optimized restriction enzyme-mediated inverse PCR method resulted in 80% compared
      to 40% deletion mutagenesis efficiency of the overlapping primer method in the
      deletion of a large area (411 bp) from a large malaria gene (PfAdoMetDC/ODC, gene
      size 4257 bp). In contrast, deletion mutagenesis methods such as the well-known
      QuickChange site-directed mutagenesis, ExSite and inverse PCR methods produced
      insignificant results. A 100% mutagenesis efficiency was obtained with the
      restriction enzyme-mediated inverse PCR method to delete 618 bp from a smaller
      gene (PfPdxK, gene size 1536 bp). CONCLUSION: An efficient method was developed
      for the deletion of large areas (>100 bp) in significantly sized genes such as
      those of the A+T-rich P. falciparum genome.

PMID- 17519002
TI  - Renin-angiotensin-aldosterone system polymorphisms: a role or a hole in
      occurrence and long-term prognosis of acute myocardial infarction at young age.
AB  - BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) is involved in the
      cardiovascular homeostasis as shown by previous studies reporting a positive
      association between specific RAAS genotypes and an increased risk of myocardial
      infarction. Anyhow the prognostic role in a long-term follow-up has not been yet
      investigated. Aim of the study was to evaluate the influence of the most studied
      RAAS genetic Single Nucleotide Polymorphisms (SNPs) on the occurrence and the
      long-term prognosis of acute myocardial infarction (AMI) at young age in an
      Italian population. METHODS: The study population consisted of 201 patients and
      201 controls, matched for age and sex (mean age 40 +/- 4 years; 90.5% males). The
      most frequent conventional risk factors were smoke (p < 0.001), family history
      for coronary artery diseases (p < 0.001), hypercholesterolemia (p = 0.001) and
      hypertension (p = 0.002). The tested genetic polymorphisms were angiotensin
      converting enzyme insertion/deletion (ACE I/D), angiotensin II type 1 receptor
      (AGTR1) A1166C and aldosterone synthase (CYP11B2) C-344T. Considering a long-term
      follow-up (9 +/- 4 years) we compared genetic polymorphisms of patients with and
      without events (cardiac death, myocardial infarction, revascularization
      procedures). RESULTS: We found a borderline significant association of occurrence
      of AMI with the ACE D/I polymorphism (DD genotype, 42% in cases vs 31% in
      controls; p = 0.056). DD genotype remained statistically involved in the
      incidence of AMI also after adjustment for clinical confounders. On the other
      hand, during the 9-year follow-up (65 events, including 13 deaths) we found a
      role concerning the AGTR1: the AC heterozygous resulted more represented in the
      event group (p = 0.016) even if not independent from clinical confounders. Anyhow
      the Kaplan-Meier event free curves seem to confirm the unfavourable role of this
      polymorphism. CONCLUSION: Polymorphisms in RAAS genes can be important in the
      onset of a first AMI in young patients (ACE, CYP11B2 polymorphisms), but not in
      the disease progression after a long follow-up period. Larger collaborative
      studies are needed to confirm these results.

PMID- 17519003
TI  - In silico identification of functional divergence between the multiple groEL gene
      paralogs in Chlamydiae.
AB  - BACKGROUND: Heat-shock proteins are specialized molecules performing different
      and essential roles in the cell including protein degradation, folding and
      trafficking. GroEL is a 60 Kda heat-shock protein ubiquitous in bacteria and has
      been regarded as an important molecule implicated in chronic inflammatory
      processes caused by Chlamydiae infections. GroEL in Chlamydiae became duplicated
      at the origin of the Chlamydiae lineage presenting three distinct molecular
      chaperones, namely the original protein GroEL1 (Ct110), and its paralogous
      proteins GroEL2 (Ct604) and GroEL3 (Ct755). These chaperones present differential
      and independent expressions during the different stages of Chlamydiae infections
      and have been suggested to present differential physiological and regulatory
      roles. RESULTS: In this comprehensive in silico study we show that GroEL protein
      paralogs have diverged functionally after the different gene duplication events
      and that this divergence has occurred mainly between GroEL3 and GroEL1. GroEL2
      presents an intermediate functional divergence pattern from GroEL1. Our results
      point to the different protein-protein interaction patterns between GroEL
      paralogs and known GroEL protein clients supporting their functional divergence
      after groEL gene duplication. Analysis of selective constraints identifies
      periods of adaptive evolution after gene duplication that led to the fixation of
      amino acid replacements in GroEL protein domains involved in the interaction with
      GroEL protein clients. CONCLUSION: We demonstrate that GroEL protein copies in
      Chlamydiae species have diverged functionally after the gene duplication events.
      We also show that functional divergence has occurred in important functional
      regions of these GroEL proteins and that very probably have affected the
      ancestral GroEL regulatory role and protein-protein interaction patterns with
      GroEL client proteins. Most of the amino acid replacements that have affected
      interaction with protein clients and that were responsible for the functional
      divergence between GroEL paralogs were fixed by adaptive evolution after the
      groEL gene duplication events.

PMID- 17519004
TI  - Allylsilanes in the synthesis of three to seven membered rings: the silylcuprate
      strategy.
AB  - Addition of low order phenyldimethylsilylcyanocuprates to allenes followed by "in
      situ" reaction of the intermediate silylcuprate with electrophiles ("the
      silylcuprate strategy") provides new routes for the synthesis of functionalised
      allylsilanes, which undergo highly stereocontrolled silicon-assisted
      intramolecular cyclizations leading to three to seven membered ring-formation.

PMID- 17519005
TI  - Non-communicable diseases and global health governance: enhancing global
      processes to improve health development.
AB  - This paper assesses progress in the development of a global framework for
      responding to non-communicable diseases, as reflected in the policies and
      initiatives of the World Health Organization (WHO), World Bank and the UN: the
      institutions most capable of shaping a coherent global policy. Responding to the
      global burden of chronic disease requires a strategic assessment of the global
      processes that are likely to be most effective in generating commitment to policy
      change at country level, and in influencing industry behaviour. WHO has adopted a
      legal process with tobacco (the WHO Framework Convention on Tobacco Control), but
      a non-legal, advocacy-based approach with diet and physical activity (the Global
      Strategy on Diet, Physical Activity and Health). The paper assesses the merits of
      the Millennium Development Goals (MDGs) and the FCTC as distinct global processes
      for advancing health development, before considering what lessons might be
      learned for enhancing the implementation of the Global Strategy on Diet. While
      global partnerships, economic incentives, and international legal instruments
      could each contribute to a more effective global response to chronic diseases,
      the paper makes a special case for the development of international legal
      standards in select areas of diet and nutrition, as a strategy for ensuring that
      the health of future generations does not become dependent on corporate charity
      and voluntary commitments. A broader frame of reference for lifestyle-related
      chronic diseases is needed: one that draws together WHO's work in tobacco,
      nutrition and physical activity, and that envisages selective use of
      international legal obligations, non-binding recommendations, advocacy and policy
      advice as tools of choice for promoting different elements of the strategy.

PMID- 17519006
TI  - RNA quality in frozen breast cancer samples and the influence on gene expression
      analysis--a comparison of three evaluation methods using microcapillary
      electrophoresis traces.
AB  - BACKGROUND: Assessing RNA quality is essential for gene expression analysis, as
      the inclusion of degraded samples may influence the interpretation of expression
      levels in relation to biological and/or clinical parameters. RNA quality can be
      analyzed by agarose gel electrophoresis, UV spectrophotometer, or microcapillary
      electrophoresis traces, and can furthermore be evaluated using different methods.
      No generally accepted recommendations exist for which technique or evaluation
      method is the best choice. The aim of the present study was to use microcapillary
      electrophoresis traces from the Bioanalyzer to compare three methods for
      evaluating RNA quality in 24 fresh frozen invasive breast cancer tissues: 1)
      Manual method = subjective evaluation of the electropherogram, 2) Ratio Method =
      the ratio between the 28S and 18S peaks, and 3) RNA integrity number (RIN) method
      = objective evaluation of the electropherogram. The results were also related to
      gene expression profiling analyses using 27K oligonucleotide microarrays,
      unsupervised hierarchical clustering analysis and ontological mapping. RESULTS:
      Comparing the methods pair-wise, Manual vs. Ratio showed concordance (good vs.
      degraded RNA) in 20/24, Manual vs. RIN in 23/24, and Ratio vs. RIN in 21/24
      samples. All three methods were concordant in 20/24 samples. The comparison
      between RNA quality and gene expression analysis showed that pieces from the same
      tumor and with good RNA quality clustered together in most cases, whereas those
      with poor quality often clustered apart. The number of samples clustering in an
      unexpected manner was lower for the Manual (n = 1) and RIN methods (n = 2) as
      compared to the Ratio method (n = 5). Assigning the data into two groups, RIN >
      or = 6 or RIN < 6, all but one of the top ten differentially expressed genes
      showed decreased expression in the latter group; i.e. when the RNA became
      degraded. Ontological mapping using GoMiner (p < or = 0.05; > or = 3 genes
      changed) revealed deoxyribonuclease activity, collagen, regulation of cell
      adhesion, cytosolic ribosome, and NADH dehydrogenase activity, to be the five
      categories most affected by RNA quality. CONCLUSION: The results indicate that
      the Manual and RIN methods are superior to the Ratio method for evaluating RNA
      quality in fresh frozen breast cancer tissues. The objective measurement when
      using the RIN method is an advantage. Furthermore, the inclusion of samples with
      degraded RNA may profoundly affect gene expression levels.

PMID- 17519007
TI  - Evaluating the organisational climate in Italian public healthcare institutions
      by means of a questionnaire.
AB  - BACKGROUND: By means of the ICONAS project, the Healthcare Agency of an Italian
      Region developed, and used a standardised questionnaire to quantify the
      organisational climate. The aims of the project were (a) to investigate whether
      the healthcare institutions were interested in measuring climate, (b) to estimate
      the range of applicability and reliability of the instrument, (c) to analyse the
      dimensions of climate among healthcare personnel, (d) to assess the differences
      among employees with different contractual positions. METHODS: The anonymous
      questionnaire containing 50 items, each with a scale from 1 to 10, was offered to
      the healthcare organisations, to be compiled during ad hoc meetings. The data
      were sent to the central project coordinator. The differences between highly
      specialised staff (mostly physicians) and other employees were assessed after
      descriptive statistical analysis of the single items. Both Principal Component
      Analysis and Factor Analysis were used. RESULTS: Ten healthcare organisations
      agreed to participate. The questionnaire was completed by 8691 employees out of
      13202. The mean value of organisational climate was 4.79 (range 1-10). There were
      significant differences among single items and between the 2 groups of employees.
      Multivariate methods showed: (a) one principal component explained > 40% of the
      variance, (b) 7 factors summarised the data. CONCLUSION: Italian healthcare
      institutions are interested in assessing organisational phenomena, especially
      after the reforms of the nineties. The instrument was found to be applicable and
      suitable for measuring organisational climate. Administration of the
      questionnaire leads to an acceptable response rate. Climate can be described by
      means of 7 underlying dimensions.

PMID- 17519008
TI  - The NMR structure of the murine DLC2 SAM domain reveals a variant fold that is
      similar to a four-helix bundle.
AB  - BACKGROUND: The tumor suppressor DLC2 (Deleted in Liver Cancer -2) participates
      in cell signaling at the mitochondrial membrane. DLC2 is characterized by a SAM
      (sterile alpha motif) domain, a Rho GTPase activating protein (GAP) domain, and a
      START lipid transfer domain. RESULTS: Towards understanding the function of DLC2,
      we have solved the NMR solution structure of the SAM domain. The DLC2-SAM domain
      structure reveals an atypical four-helix composition that is distinct from the
      five-helix SAM domain structures that have been determined to date. From
      structural alignments, helix 3 of the canonical SAM domain appears to be replaced
      by shorter, extended secondary structure that follows a similar path. Another
      difference is demonstrated by helices 1 and 2 that form a helical hairpin that is
      situated approximately parallel to the canonical helix 5. CONCLUSION: The DLC2
      SAM domain adopts a structure that is topologically more similar to an anti
      parallel four-helix bundle than a canonical SAM domain. This alternate topology
      may allow the DLC2-SAM domain to interact with a novel set of ligands.

PMID- 17519009
TI  - Adolescent survey non-response and later risk of death. A prospective cohort
      study of 78,609 persons with 11-year follow-up.
AB  - BACKGROUND: Non-response in survey studies is a growing problem and, being
      usually selective, it leads to under- or overestimation of health outcomes in the
      follow-up. We followed both respondents and non-respondents by registry linkage
      to determine whether there is a risk of death, related to non-response at
      baseline. METHODS: Sample data of biennial surveys to 12-18-year-old Finns in
      1979-1997 were linked with national death registry up to 2001. The number of
      respondents was 62,528 (79.6%) and non-respondents 16,081 (20.4%). The average
      follow-up was 11.1 years, totalling 876,400 person-years. The risk of death
      between non-respondents and respondents was estimated by hazard ratios (HR).
      RESULTS: The number of deaths per 100,000 person-years were 229 in non
      respondents and 447 in respondents (HR 2.0, 95% CI: 1.5-2.6). The hazard ratios
      of death were for intoxication 3.2 (95% CI: 1.9-5.4), for disease 3.1 (95% CI:
      2.2-4.1), for violence-related injury 2.0 (95% CI: 1.5-2.6) and for unintentional
      injury 1.8 (95% CI: 1.3-2.4) in non-respondents vs. respondents. The association
      between non-response and death increased with age at baseline, and the increase
      persisted after the age of 25. CONCLUSION: Our study demonstrated significantly
      increased rates of death among adolescent non-respondents in a follow-up. The
      highest hazard ratios were seen in disease- and violence-related deaths. The
      death rate varied between respondents and non-respondents by death type.
      Increased rates of death persisted beyond the age of 25.

PMID- 17519010
TI  - Randomized clinical trial of artemisinin versus non-artemisinin combination
      therapy for uncomplicated falciparum malaria in Madagascar.
AB  - BACKGROUND: Data concerning antimalarial combination treatment for uncomplicated
      malaria in Madagascar are largely lacking. Randomized clinical trial was designed
      to assess therapeutic efficacies of chloroquine (CQ), amodiaquine (AQ),
      sulphadoxine-pyrimethamine (SP), amodiaquine plus sulphadoxine-pyrimethamine
      combination (AQ+SP) and artesunate plus amodiaquine combination (AQ+AS). METHODS:
      287 children between 6 months and 15 years of age, with uncomplicated falciparum
      malaria, were enrolled in the study. Primary endpoints were the day-14 and day-28
      risks of parasitological failure, either unadjusted or adjusted by genotyping.
      RESULTS: All treatment regimens, except for CQ treatment, gave clinical cure
      rates above 97% by day-14 and 92% by day-28 (PCR-corrected). AQ+SP was as
      effective as AQ+AS. The risk of new infection within the month after therapy was
      generally higher for AQ+AS than AQ+SP. CONCLUSION: These findings show that the
      inexpensive and widely available combination AQ+SP may be valuable in for the
      treatment of uncomplicated malaria in Madagascar and could have an important role
      in this country, where much of the drugs administered go to patients who do not
      have malaria.

PMID- 17519011
TI  - Antimicrobial resistance predicts death in Tanzanian children with bloodstream
      infections: a prospective cohort study.
AB  - BACKGROUND: Bloodstream infection is a common cause of hospitalization, morbidity
      and death in children. The impact of antimicrobial resistance and HIV infection
      on outcome is not firmly established. METHODS: We assessed the incidence of
      bloodstream infection and risk factors for fatal outcome in a prospective cohort
      study of 1828 consecutive admissions of children aged zero to seven years with
      signs of systemic infection. Blood was obtained for culture, malaria microscopy,
      HIV antibody test and, when necessary, HIV PCR. We recorded data on clinical
      features, underlying diseases, antimicrobial drug use and patients' outcome.
      RESULTS: The incidence of laboratory-confirmed bloodstream infection was 13.9%
      (255/1828) of admissions, despite two thirds of the study population having
      received antimicrobial therapy prior to blood culture. The most frequent isolates
      were klebsiella, salmonellae, Escherichia coli, enterococci and Staphylococcus
      aureus. Furthermore, 21.6% had malaria and 16.8% HIV infection. One third (34.9%)
      of the children with laboratory-confirmed bloodstream infection died. The
      mortality rate from Gram-negative bloodstream infection (43.5%) was more than
      double that of malaria (20.2%) and Gram-positive bloodstream infection (16.7%).
      Significant risk factors for death by logistic regression modeling were
      inappropriate treatment due to antimicrobial resistance, HIV infection, other
      underlying infectious diseases, malnutrition and bloodstream infection caused by
      Enterobacteriaceae, other Gram-negatives and candida. CONCLUSION: Bloodstream
      infection was less common than malaria, but caused more deaths. The frequent use
      of antimicrobials prior to blood culture may have hampered the detection of
      organisms susceptible to commonly used antimicrobials, including pneumococci, and
      thus the study probably underestimates the incidence of bloodstream infection.
      The finding that antimicrobial resistance, HIV-infection and malnutrition predict
      fatal outcome calls for renewed efforts to curb the further emergence of
      resistance, improve HIV care and nutrition for children.

PMID- 17519012
TI  - Correlation-maximizing surrogate gene space for visual mining of gene expression
      patterns in developing barley endosperm tissue.
AB  - BACKGROUND: Micro- and macroarray technologies help acquire thousands of gene
      expression patterns covering important biological processes during plant
      ontogeny. Particularly, faithful visualization methods are beneficial for
      revealing interesting gene expression patterns and functional relationships of
      coexpressed genes. Such screening helps to gain deeper insights into regulatory
      behavior and cellular responses, as will be discussed for expression data of
      developing barley endosperm tissue. For that purpose, high-throughput
      multidimensional scaling (HiT-MDS), a recent method for similarity-preserving
      data embedding, is substantially refined and used for (a) assessing the quality
      and reliability of centroid gene expression patterns, and for (b) derivation of
      functional relationships of coexpressed genes of endosperm tissue during barley
      grain development (0-26 days after flowering). RESULTS: Temporal expression
      profiles of 4824 genes at 14 time points are faithfully embedded into two
      dimensional displays. Thereby, similar shapes of coexpressed genes get closely
      grouped by a correlation-based similarity measure. As a main result, by using
      power transformation of correlation terms, a characteristic cloud of points with
      bipolar sandglass shape is obtained that is inherently connected to expression
      patterns of pre-storage, intermediate and storage phase of endosperm development.
      CONCLUSION: The new HiT-MDS-2 method helps to create global views of expression
      patterns and to validate centroids obtained from clustering programs.
      Furthermore, functional gene annotation for developing endosperm barley tissue is
      successfully mapped to the visualization, making easy localization of major
      centroids of enriched functional categories possible.

PMID- 17519013
TI  - Rapid and specific biotin labelling of the erythrocyte surface antigens of both
      cultured and ex-vivo Plasmodium parasites.
AB  - BACKGROUND: Sensitive detection of parasite surface antigens expressed on
      erythrocyte membranes is necessary to further analyse the molecular pathology of
      malaria. This study describes a modified biotin labelling/osmotic lysis method
      which rapidly produces membrane extracts enriched for labelled surface antigens
      and also improves the efficiency of antigen recovery compared with traditional
      detergent extraction and surface radio-iodination. The method can also be used
      with ex-vivo parasites. METHODS: After surface labelling with biotin in the
      presence of the inhibitor furosemide, detergent extraction and osmotic lysis
      methods of enriching for the membrane fractions were compared to determine the
      efficiency of purification and recovery. Biotin-labelled proteins were identified
      on silver-stained SDS-polyacrylamide gels. RESULTS: Detergent extraction and
      osmotic lysis were compared for their capacity to purify biotin-labelled
      Plasmodium falciparum and Plasmodium chabaudi erythrocyte surface antigens. The
      pellet fraction formed after osmotic lysis of P. falciparum-infected erythrocytes
      is notably enriched in surface antigens, including PfEMP1, when compared to
      detergent extraction. There is also reduced co-extraction of host proteins such
      as spectrin and Band 3. CONCLUSION: Biotinylation and osmotic lysis provides an
      improved method to label and purify parasitised erythrocyte surface antigen
      extracts from both in vitro and ex vivo Plasmodium parasite preparations.

PMID- 17519014
TI  - Education, sense of mastery and mental health: results from a nation wide health
      monitoring study in Norway.
AB  - BACKGROUND: Earlier studies have shown that people with low level of education
      have increased rates of mental health problems. The aim of the present study is
      to investigate the association between level of education and psychological
      distress, and to explore to which extent the association is mediated by sense of
      mastery, and social variables like social support, negative life events,
      household income, employment and marital status. METHODS: The data for the study
      were obtained from the Level of Living Survey conducted by Statistics Norway in
      2002. Data on psychological distress and psychosocial variables were gathered by
      a self-administered questionnaire, whereas socio-demographic data were based on
      register statistics. Psychological distress was measured by Hopkins Symptom
      Checklist 25 items. RESULTS: There was a significant association between low
      level of education and psychological distress in both genders, the association
      being strongest in women aged 55-67 years. Low level of education was also
      significantly associated with low sense of mastery, low social support, many
      negative life events (only in men), low household income and unemployment,. Sense
      of mastery emerged as a strong mediating variable between level of education and
      psychological distress, whereas the other variables played a minor role when
      adjusting for sense of mastery. CONCLUSION: Low sense of mastery seems to account
      for much of the association between low educational level and psychological
      distress, and should be an important target in mental health promotion for groups
      with low level of education.

PMID- 17519015
TI  - Important roles of multiple Sp1 binding sites and epigenetic modifications in the
      regulation of the methionine sulfoxide reductase B1 (MsrB1) promoter.
AB  - BACKGROUND: Methionine sulfoxide reductases (Msrs) are enzymes that catalyze the
      reduction of oxidized methionine residues. Most organisms that were genetically
      modified to lack the MsrA gene have shown shortening of their life span.
      Methionine sulfoxide reductases B (MsrB) proteins codified by three separate
      genes, named MsrB1, MsrB2, and MsrB3, are included in the Msrs system. To date,
      the mechanisms responsible for the transcriptional regulation of MsrB genes have
      not been reported. The aim of this study was to investigate the regulation of
      MsrB1 selenoprotein levels through transcriptional regulation of the MsrB1 gene
      in MDA-MB231 and MCF-7 breast carcinoma cell lines. RESULTS: A MsrB1 gene
      promoter is located 169 base pairs upstream from the transcription start site. It
      contains three Sp1 binding sites which are sufficient for maximal promoter
      activity in transient transfection experiments. High levels of MsrB1 transcript,
      protein and promoter activity were detected in low metastatic MCF7 human breast
      cancer cells. On the contrary, very low levels of both MsrB1 transcript and
      promoter activity were detected in the highly metastatic counterpart MDA-MB231
      cells.A pivotal role for Sp1 in the constitutive expression of the MsrB1 gene was
      demonstrated through transient expression of mutant MsrB1 promoter-reporter gene
      constructs and chromatin immunoprecipitation experiments. Since Sp1 is
      ubiquitously expressed, these sites, while necessary, are not sufficient to
      explain the patterns of gene expression of MsrB1 in various human breast cancer
      cells. MDA-MB231 cells can be induced to express MsrB1 by treatment with 5-Aza-2'
      deoxycytidine, a demethylating agent. Therefore, the MsrB1 promoter is controlled
      by epigenetic modifications. CONCLUSION: The results of this study provide the
      first insights into the transcriptional regulation of the human MsrB1 gene,
      including the discovery that the Sp1 transcription factor may play a central role
      in its expression. We also demonstrated that the MsrB1 promoter activity appears
      to be controlled by epigenetic modifications such as methylation.

PMID- 17519016
TI  - Reproducibility of postural control measurement during unstable sitting in low
      back pain patients.
AB  - BACKGROUND: Postural control tests like standing and sitting stabilometry are
      widely used to evaluate neuromuscular control related to trunk balance in low
      back pain patients. Chronic low back pain patients have lesser postural control
      compared to healthy subjects. Few studies have assessed the reproducibility of
      the centre of pressure deviations and to our knowledge no studies have
      investigated the reproducibility of three-dimensional kinematics of postural
      control tests in a low back pain population. Therefore the aim of this study was
      to assess the test-retest reproducibility of a seated postural control test in
      low back pain patients. METHODS: Postural control in low back pain patients was
      registered by a three dimensional motion analysis system combined with a force
      plate. Sixteen chronic low back pain patients having complaints for at least six
      months, were included based on specific clinical criteria. Every subject
      performed 4 postural control tests. Every test was repeated 4 times and lasted 40
      seconds. The force plate registered the deviations of the centre of pressure. A
      Vicon-612-datastation, equipped with 7 infra-red M1 camera's, was used to track
      13 markers attached to the torso and pelvis in order to estimate their angular
      displacement in the 3 cardinal planes. RESULTS: All Intraclass Correlation
      Coefficients (ICC) calculated for the force plate variables did not exceed 0.73
      (ranging between 0.11 and 0.73). As for the torso, ICC's of the mean flexion
      extension and rotation angles ranged from 0.65 to 0.93 and of the mean lateral
      flexion angle from 0.50 to 0.67. For the pelvis the ICC of the mean flexion
      extension angle varied between 0.66 and 0.83, the mean lateral flexion angle
      between 0.16 and 0.81 and the mean rotation angle between 0.40 and 0.62.
      Consecutive data suggest that the low test-retest reproducibility is probably due
      to a learning effect. CONCLUSION: The test-retest reproducibility of these
      postural control tests in an unstable sitting position can globally be considered
      as rather moderate. In order to improve the test-retest reproducibility, a
      learning period may be advisable at the beginning of the test.

PMID- 17519017
TI  - The frequency of missed test results and associated treatment delays in a highly
      computerized health system.
AB  - BACKGROUND: Diagnostic errors associated with the failure to follow up on
      abnormal diagnostic studies ("missed results") are a potential cause of treatment
      delay and a threat to patient safety. Few data exist concerning the frequency of
      missed results and associated treatment delays within the Veterans Health
      Administration (VA). OBJECTIVE: The primary objective of the current study was to
      assess the frequency of missed results and resulting treatment delays encountered
      by primary care providers in VA clinics. METHODS: An anonymous on-line survey of
      primary care providers was conducted as part of the health systems ongoing
      quality improvement programs. We collected information from providers concerning
      their clinical effort (e.g., number of clinic sessions, number of patient visits
      per session), number of patients with missed abnormal test results, and the
      number and types of treatment delays providers encountered during the two week
      period prior to administration of our survey. RESULTS: The survey was completed
      by 106 out of 198 providers (54 percent response rate). Respondents saw and
      average of 86 patients per 2 week period. Providers encountered 64 patients with
      missed results during the two week period leading up to the study and 52 patients
      with treatment delays. The most common missed results included imaging studies
      (29 percent), clinical laboratory (22 percent), anatomic pathology (9 percent),
      and other (40 percent). The most common diagnostic delays were cancer (34
      percent), endocrine problems (26 percent), cardiac problems (16 percent), and
      others (24 percent). CONCLUSION: Missed results leading to clinically important
      treatment delays are an important and likely underappreciated source of
      diagnostic error.

PMID- 17519018
TI  - GOSim--an R-package for computation of information theoretic GO similarities
      between terms and gene products.
AB  - BACKGROUND: With the increased availability of high throughput data, such as DNA
      microarray data, researchers are capable of producing large amounts of biological
      data. During the analysis of such data often there is the need to further explore
      the similarity of genes not only with respect to their expression, but also with
      respect to their functional annotation which can be obtained from Gene Ontology
      (GO). RESULTS: We present the freely available software package GOSim, which
      allows to calculate the functional similarity of genes based on various
      information theoretic similarity concepts for GO terms. GOSim extends existing
      tools by providing additional lately developed functional similarity measures for
      genes. These can e.g. be used to cluster genes according to their biological
      function. Vice versa, they can also be used to evaluate the homogeneity of a
      given grouping of genes with respect to their GO annotation. GOSim hence provides
      the researcher with a flexible and powerful tool to combine knowledge stored in
      GO with experimental data. It can be seen as complementary to other tools that,
      for instance, search for significantly overrepresented GO terms within a given
      group of genes. CONCLUSION: GOSim is implemented as a package for the statistical
      computing environment R and is distributed under GPL within the CRAN project.

PMID- 17519019
TI  - Haemoglobin and haematocrit: is the threefold conversion valid for assessing
      anaemia in malaria-endemic settings?
AB  - BACKGROUND: Anaemic status is determined by haemoglobin using the HemoCue system
      or haematocrit measurements, and a threefold conversion is commonly used to
      equate the two measures (haemoglobin = haematocrit/3). The validity of this
      conversion in malaria endemic settings was assessed. METHODS: Concurrent measures
      of haemoglobin and centrifuged haematocrit in children aged 6-59 months were
      compared by modelling the difference between the two measures against their
      average. A random effects linear regression of the difference of the measures on
      their average was used to describe the line of best agreement and 95% limits of
      agreement for these two measures over a range of values after adjusting for
      statistically significant covariates. RESULTS: There was a consistent bias
      between the two measures, with haemoglobin less than haematocrit/3 in 87%
      (899/1,030) of observations. This difference was non-uniform, decreasing with the
      average measure, i.e. less difference at higher haemoglobin and haematocrit
      values. In these studies, use of haematocrit would have underestimated the
      prevalence of anaemia by misclassifying 10% (89/920) of individuals with
      haemoglobin < 11 g/dl, 66% (252/380) of individuals with haemoglobin < 8 g/dl and
      100% (23/23) of individuals with haemoglobin < 5 g/dl. The mean difference
      between the measures was greater in males than females, increased with age
      between 6-59 months, and was greater in the wet than dry season suggesting that
      the relationship between haemoglobin and haematocrit may be modified by exposure
      to malaria. CONCLUSION: The regression model indicated that the standard
      threefold conversion from haematocrit to haemoglobin underestimates the
      prevalence of haemoglobin < 11 g/dl in children under five years of age in
      malaria endemic settings. This bias was more acute for more severe anaemia
      defined by haemoglobin < 8 g/dl and haemoglobin < 5 g/dl. This has important
      implications for the comparability of studies using these different measures.
      Direct determination of haemoglobin should be the measurement of choice for
      assessing anaemia outcomes in malaria intervention trials and surveys.

PMID- 17519020
TI  - Correlates of women's cancer screening and contraceptive knowledge among female
      emergency department patients.
AB  - BACKGROUND: Lack of knowledge regarding preventive health services for women
      might impede campaigns to expand these services in the emergency department
      setting. For 18-55-year-old English-speaking women visiting an urban emergency
      department, we aimed to: (1) Ascertain their knowledge regarding the
      applicability, purpose, and recommended intervals of three women's cancer
      screening and three contraceptive methods; and (2) Determine if patient age,
      race/ethnicity, medical insurance status, and current or recent usage of these
      methods are associated with greater or lesser knowledge about them. METHODS:
      Emergency department-based survey on recent or current usage and knowledge about
      Pap smears, breast self-examinations, mammograms, condoms, birth control, and
      emergency contraception. Analyses included calculation of summary statistics and
      creation of multivariable logistic regression models. RESULTS: Of 1,100 patients
      eligible for the study, 69.9% agreed to participate. Most of the participants
      were < age 35, white, single (never married and no partner), Catholic, and had
      private medical insurance. Participant's recent or current usage of a particular
      cancer screening or contraceptive method varied by type of method: Pap smear
      within the past year (69.1%), breast self-exam within the past month (45.5%),
      mammogram within the past year (65.7% for women age 45-55), condom usage during
      every episode of sexual intercourse (15.4%), current usage of birth control pills
      (17.8%), and ever use of emergency contraception (9.3%). The participants
      correctly answered 87.9% of all survey questions about condoms, 82.5% about birth
      control pills, 78.5% about breast self-exams, 52.9% about Pap smears, 35.4% about
      mammograms, and 25.0% about emergency contraception. In multivariable logistic
      regression models, survey participants who had private medical insurance and
      those who recently or currently used a given screening or contraceptive method
      had a greater odds of correctly answering all questions about each cancer
      screening or contraceptive method. CONCLUSION: Although these female ED patients
      demonstrated strong knowledge on some women's cancer screening and contraceptive
      methods, there were several areas of knowledge deficit. Women without private
      medical insurance and those who have not used a particular cancer screening or
      contraceptive method demonstrated less knowledge. Reduced knowledge about women's
      cancer screening and contraceptive methods should be considered during clinical
      encounters and when instituting or evaluating emergency department-based
      initiatives that assess the need for these methods.

PMID- 17519021
TI  - Coordinated regulation of Myc trans-activation targets by Polycomb and the
      Trithorax group protein Ash1.
AB  - BACKGROUND: The Myc oncoprotein is a transcriptional regulator whose function is
      essential for normal development. Myc is capable of binding to 10% of the
      mammalian genome, and it is unclear how a developing embryo controls the DNA
      binding of its abundant Myc proteins in order to avoid Myc's potential for
      inducing tumorigenesis. RESULTS: To identify chromatin binding proteins with a
      potential role in controlling Myc activity, we established a genetic assay for
      dMyc activity in Drosophila. We conducted a genome-wide screen using this assay,
      and identified the Trithorax Group protein Ash1 as a modifier of dMyc activity.
      Ash1 is a histone methyltransferase known for its role in opposing repression by
      Polycomb. Using RNAi in the embryo and Affymetrix microarrays, we show that ash1
      RNAi causes the increased expression of many genes, suggesting that it is
      directly or indirectly required for repression in the embryo, in contrast to its
      known role in maintenance of activation. Many of these genes also respond
      similarly upon depletion of Pc and pho transcripts, as determined by concurrent
      microarray analysis of Pc and pho RNAi embryos, suggesting that the three are
      required for low levels of expression of a common set of targets. Further, many
      of these overlapping targets are also activated by Myc overexpression. We
      identify a second group of genes whose expression in the embryo requires Ash1,
      consistent with its previously established role in maintenance of activation. We
      find that this second group of Ash1 targets overlaps those activated by Myc and
      that ectopic Myc overcomes their requirement for Ash1. CONCLUSION: Genetic,
      genomic and chromatin immunoprecipitation data suggest a model in which Pc, Ash1
      and Pho are required to maintain a low level of expression of embryonic targets
      of activation by Myc, and that this occurs, directly or indirectly, by a
      combination of disparate chromatin modifications.

PMID- 17519022
TI  - Monitoring of gene knockouts: genome-wide profiling of conditionally essential
      genes.
AB  - We have developed a new microarray-based genetic technique, named MGK (Monitoring
      of Gene Knockouts), for genome-wide identification of conditionally essential
      genes. MGK identified bacterial genes that are critical for fitness in the
      absence of aromatic amino acids, and was further applied to identify genes whose
      inactivation causes bacterial cell death upon exposure to the bacteriostatic
      antibiotic chloramphenicol. Our findings suggest that MGK can serve as a robust
      tool in functional genomics studies.

PMID- 17519023
TI  - Analysis of 14 BAC sequences from the Aedes aegypti genome: a benchmark for
      genome annotation and assembly.
AB  - BACKGROUND: Aedes aegypti is the principal vector of yellow fever and dengue
      viruses throughout the tropical world. To provide a set of manually curated and
      annotated sequences from the Ae. aegypti genome, 14 mapped bacterial artificial
      chromosome (BAC) clones encompassing 1.57 Mb were sequenced, assembled and
      manually annotated using a combination of computational gene-finding, expressed
      sequence tag (EST) matches and comparative protein homology. PCR and sequencing
      were used to experimentally confirm expression and sequence of a subset of these
      transcripts. RESULTS: Of the 51 manual annotations, 50 and 43 demonstrated a high
      level of similarity to Anopheles gambiae and Drosophila melanogaster genes,
      respectively. Ten of the 12 BAC sequences with more than one annotated gene
      exhibited synteny with the A. gambiae genome. Putative transcripts from eight BAC
      clones were found in multiple copies (two copies in most cases) in the Aedes
      genome assembly, which point to the probable presence of haplotype polymorphisms
      and/or misassemblies. CONCLUSION: This study not only provides a benchmark set of
      manually annotated transcripts for this genome that can be used to assess the
      quality of the auto-annotation pipeline and the assembly, but it also looks at
      the effect of a high repeat content on the genome assembly and annotation
      pipeline.

PMID- 17519024
TI  - Peer assessment of outpatient consultation letters--feasibility and satisfaction.
AB  - BACKGROUND: Written correspondence is one of the most important forms of
      communication between health care providers, yet there is little feedback
      provided to specialists. The objective of this study was to determine the
      feasibility and satisfaction of a peer assessment program on consultation letters
      and to determine inter-rater reliability between family physicians and
      specialists. METHODS: A rating scale of nine 5-point Likert scale items including
      specific content, style items, education value of the letter and an overall
      rating was developed from a previous validated tool. Nine Internal Medicine
      specialists/subspecialists from two tertiary care centres submitted 10 letters
      with patient and physician identifiers removed. Two Internal Medicine
      specialists, and 2 family physicians from the other centre rated each letter (to
      protect writer anonymity). A satisfaction survey was sent to each writer and
      rater after collation of the results. A follow-up survey was sent 6-8 months
      later. RESULTS: There was a high degree of satisfaction with the process and
      feedback. The rating scale information was felt to be useful and appropriate for
      evaluating the quality of consultation letters by 6/7 writers. 5/7 seven writers
      felt that the feedback they received resulted in immediate changes to their
      letters. Six months later, 6/9 writers indicated they had maintained changes in
      their letters. Raters rank ordered letters similarly (Cronbach's alpha 0.57-0.84)
      but mean scores were highly variant. At site 1 there were significant differences
      in scoring brevity (p < 0.01) between family physician and specialist raters;
      whereas, at site 2 there were differences in scoring of history (p < 0.01),
      physical examination (p < 0.01) and educational value (p < 0.01) of the letter.
      CONCLUSION: Most participants found peer assessment of letters feasible and
      beneficial and longstanding changes occurred in some individuals. Family
      physicians and specialists appear to have different expectations on some items.
      Further studies on reliability and validity, with a larger sample, are required
      before high stakes professional assessments include consultation letters.

PMID- 17519025
TI  - Hinge Atlas: relating protein sequence to sites of structural flexibility.
AB  - BACKGROUND: Relating features of protein sequences to structural hinges is
      important for identifying domain boundaries, understanding structure-function
      relationships, and designing flexibility into proteins. Efforts in this field
      have been hampered by the lack of a proper dataset for studying characteristics
      of hinges. RESULTS: Using the Molecular Motions Database we have created a Hinge
      Atlas of manually annotated hinges and a statistical formalism for calculating
      the enrichment of various types of residues in these hinges. CONCLUSION: We found
      various correlations between hinges and sequence features. Some of these are
      expected; for instance, we found that hinges tend to occur on the surface and in
      coils and turns and to be enriched with small and hydrophilic residues. Others
      are less obvious and intuitive. In particular, we found that hinges tend to
      coincide with active sites, but unlike the latter they are not at all conserved
      in evolution. We evaluate the potential for hinge prediction based on sequence.
      Motions play an important role in catalysis and protein-ligand interactions.
      Hinge bending motions comprise the largest class of known motions. Therefore it
      is important to relate the hinge location to sequence features such as residue
      type, physicochemical class, secondary structure, solvent exposure, evolutionary
      conservation, and proximity to active sites. To do this, we first generated the
      Hinge Atlas, a set of protein motions with the hinge locations manually
      annotated, and then studied the coincidence of these features with the hinge
      location. We found that all of the features have bearing on the hinge location.
      Most interestingly, we found that hinges tend to occur at or near active sites
      and yet unlike the latter are not conserved. Less surprisingly, we found that
      hinge residues tend to be small, not hydrophobic or aliphatic, and occur in turns
      and random coils on the surface. A functional sequence based hinge predictor was
      made which uses some of the data generated in this study. The Hinge Atlas is made
      available to the community for further flexibility studies.

PMID- 17519026
TI  - Cystatin C and beta2-microglobulin: markers of glomerular filtration in
      critically ill children.
AB  - INTRODUCTION: Parameters allowing regular evaluation of renal function in a
      paediatric intensive care unit (PICU) are not optimal. The aim of the present
      study was to analyse the utility of serum cystatin C and beta2-microglobulin
      (B2M) in detecting decreased glomerular filtration rate in critically ill
      children. METHODS: This was a prospective, observational study set in an eight
      bed PICU. Twenty-five children were included. The inverses of serum creatinine,
      cystatin C, and B2M were correlated with creatinine clearance (CrC) using a 24
      hour urine sample and CrC estimation by Schwartz formula (Schwartz). The
      diagnostic value of serum creatinine, cystatin C, and B2M to identify a
      glomerular filtration rate under 80 ml/minute per 1.73 m(2) was evaluated using
      receiver operating characteristic (ROC) curve analysis. RESULTS: Mean age was 2.9
      years (range, 0.1 to 13.9 years). CrC was less than 80 ml/minute per 1.73 m(2) in
      14 children, and Schwartz was less than 80 ml/minute per 1.73 m(2) in 9 children.
      Correlations between inverse of B2M and CrC (r = 0.477) and between inverse of
      B2M and Schwartz (r = 0.697) were better than correlations between inverse of
      cystatin C and CrC (r = 0.390) or Schwartz (r = 0.586) and better than
      correlations between inverse of creatinine and CrC (r = 0.104) or Schwartz (r =
      0.442). The ability of serum cystatin C and B2M to identify a CrC rate and a
      Schwartz CrC rate under 80 ml/minute per 1.73 m(2) was better than that of
      creatinine (areas under the ROC curve: 0.851 and 0.792 for cystatin C, 0.802 and
      0.799 for B2M, and 0.633 and 0.625 for creatinine). CONCLUSION: Serum cystatin C
      and B2M were confirmed as easy and useful markers, better than serum creatinine,
      to detect acute kidney injury in critically ill children.

PMID- 17519027
TI  - Communication and marketing as tools to cultivate the public's health: a proposed
      "people and places" framework.
AB  - BACKGROUND: Communication and marketing are rapidly becoming recognized as core
      functions, or core competencies, in the field of public health. Although these
      disciplines have fostered considerable academic inquiry, a coherent sense of
      precisely how these disciplines can inform the practice of public health has been
      slower to emerge. DISCUSSION: In this article we propose a framework--based on
      contemporary ecological models of health--to explain how communication and
      marketing can be used to advance public health objectives. The framework
      identifies the attributes of people (as individuals, as social networks, and as
      communities or populations) and places that influence health behaviors and
      health. Communication, i.e., the provision of information, can be used in a
      variety of ways to foster beneficial change among both people (e.g., activating
      social support for smoking cessation among peers) and places (e.g., convincing
      city officials to ban smoking in public venues). Similarly, marketing, i.e., the
      development, distribution and promotion of products and services, can be used to
      foster beneficial change among both people (e.g., by making nicotine replacement
      therapy more accessible and affordable) and places (e.g., by providing city
      officials with model anti-tobacco legislation that can be adapted for use in
      their jurisdiction). SUMMARY: Public health agencies that use their communication
      and marketing resources effectively to support people in making healthful
      decisions and to foster health-promoting environments have considerable
      opportunity to advance the public's health, even within the constraints of their
      current resource base.

PMID- 17519028
TI  - The NRG1 exon 11 missense variant is not associated with autism in the Central
      Valley of Costa Rica.
AB  - BACKGROUND: We are conducting a genetic study of autism in the isolated
      population of the Central Valley of Costa Rica (CVCR). A novel Neuregulin 1
      (NRG1) missense variant (exon 11 G>T) was recently associated with psychosis and
      schizophrenia (SCZ) in the same population isolate. METHODS: We genotyped the
      NRG1 exon 11 missense variant in 146 cases with autism, or autism spectrum
      disorder, with CVCR ancestry, and both parents when available (N = 267 parents)
      from 143 independent families. Additional microsatellites were genotyped to
      examine haplotypes bearing the exon 11 variant. RESULTS: The NRG1 exon 11 G>T
      variant was found in 4/146 cases including one de novo occurrence. The frequency
      of the variant in case chromosomes was 0.014 and 0.045 in the parental non
      transmitted chromosomes. At least 6 haplotypes extending 0.229 Mb were associated
      with the T allele. Three independent individuals, with no personal or family
      history of psychiatric disorder, shared at least a 1 megabase haplotype 5' to the
      T allele. CONCLUSION: The NRG1 exon 11 missense variant is not associated with
      autism in the CVCR.

PMID- 17519029
TI  - Plexin-B1 plays a redundant role during mouse development and in tumour
      angiogenesis.
AB  - BACKGROUND: Plexins are a large family of transmembrane receptors for the
      Semaphorins, known for their role in the assembly of neural circuitry. More
      recently, Plexins have been implicated in diverse biological functions, including
      vascular growth, epithelial tissue morphogenesis and tumour development. In
      particular, PlexinB1, the receptor for Sema4D, has been suggested to play a role
      in neural development and in tumour angiogenesis, based on in vitro studies.
      However, the tissue distribution of PlexinB1 has not been extensively studied and
      the functional relevance of this receptor in vivo still awaits experimental
      testing. In order to shed light on PlexinB1 function in vivo, we therefore
      undertook the genomic targeting of the mouse gene to obtain loss of function
      mutants. RESULTS: This study shows that PlexinB1 receptor and its putative
      ligand, Sema4D, have a selective distribution in nervous and epithelial tissues
      during development and in the adult. PlexinB1 and Sema4D show largely
      complementary cell distribution in tissues, consistent with the idea that
      PlexinB1 acts as the receptor for Sema4D in vivo. Interestingly, PlexinB1 is also
      expressed in certain tissues in the absence of Sema4D, suggesting Sema4D
      independent activities. High expression of PlexinB1 was found in lung, kidney,
      liver and cerebellum. Mutant mice lacking expression of semaphorin receptor
      PlexinB1 are viable and fertile. Although the axon collapsing activity of Sema4D
      is impaired in PlexinB1 deficient neurons, we could not detect major defects in
      development, or in adult histology and basic functional parameters of tissues
      expressing PlexinB1. Moreover, in the absence of PlexinB1 the angiogenic response
      induced by orthotopically implanted tumours was not affected, suggesting that the
      expression of this semaphorin receptor in endothelial cells is redundant.
      CONCLUSION: Our expression analysis suggests a multifaceted role of PlexinB1
      during mouse development and tissue homeostasis in the adult. Nonetheless, the
      genetic deletion of PlexinB1 does not result in major developmental defects or
      clear functional abnormalities. We infer that PlexinB1 plays a redundant role in
      mouse development and it is not strictly required for tumour induced
      angiogenesis.

PMID- 17519030
TI  - Recovery of transplantable organs after cardiac or circulatory death:
      transforming the paradigm for the ethics of organ donation.
AB  - Organ donation after cardiac or circulatory death (DCD) has been introduced to
      increase the supply of transplantable organs. In this paper, we argue that the
      recovery of viable organs useful for transplantation in DCD is not compatible
      with the dead donor rule and we explain the consequential ethical and legal
      ramifications. We also outline serious deficiencies in the current consent
      process for DCD with respect to disclosure of necessary elements for voluntary
      informed decision making and respect for the donor's autonomy. We compare two
      alternative proposals for increasing organ donation consent in society: presumed
      consent and mandated choice. We conclude that proceeding with the recovery of
      transplantable organs from decedents requires a paradigm change in the ethics of
      organ donation. The paradigm change to ensure the legitimacy of DCD practice must
      include: (1) societal agreement on abandonment of the dead donor rule, (2)
      legislative revisions reflecting abandonment of the dead donor rule, and (3)
      requirement of mandated choice to facilitate individual participation in organ
      donation and to ensure that decisions to participate are made in compliance with
      the societal values of respect for autonomy and self-determination.

PMID- 17519031
TI  - Acceptability and efficacy of intra-rectal quinine alkaloids as a pre-transfer
      treatment of non-per os malaria in peripheral health care facilities in Mopti,
      Mali.
AB  - BACKGROUND: The acceptability and efficacy of a new kit with a new formulation of
      quinine alkaloids designed for the intra-rectal administration in the treatment
      of non-per os malaria was assessed in the peripheral health care system of Mopti,
      Mali. METHODS: A single-arm trial was conducted from August 2003 to January 2004.
      An initial dose of diluted quinine alkaloids (20 mg/kg Quinimax) was administered
      by the intra-rectal route to children with presumptive non per-os malaria at six
      peripheral heath care centres. The children were then referred to two referral
      hospitals where standard inpatient care including intravenous route were
      routinely provided. A malaria thick smear was done at inclusion and a second
      malaria thick smear after arrival at the referral facility, where a more complete
      clinical examination and laboratory testing was done to confirm diagnosis.
      Confirmed cases of severe malaria or others diseases were treated according to
      national treatment guidelines. Cases of non per-os malaria received a second dose
      of intra rectal quinine alkaloids. Primary outcome was acceptability of the intra
      rectal route by children and their parents as well as the ease to handle the kit
      by health care workers. RESULTS: The study included 134 children with a median
      age of 33 months and 53.7% were male. Most of the children (67%) and 92% of
      parents or guardians readily accepted the intra-rectal route; 84% of health care
      workers found the kit easy to use. At the peripheral health care centres, 32% of
      children had a coma score < or = 3 and this was reduced to 10% at the referral
      hospital, following one dose of intra-rectal quinine alkaloids (IRQA). The mean
      time to availability of oral route treatment was 1.8 +/- 1.1 days. Overall, 73%
      of cases were confirmed severe malaria and for those the case fatality rate was
      7.2%. CONCLUSION: IRQA was well accepted by children, their parents/guardians and
      by the health workers at peripheral health facilities in Mopti, Mali. There was
      also a quick recovery from deep coma and a reduced case fatality rate in severe
      malaria.

PMID- 17519032
TI  - Transcriptional profiling of Arabidopsis heat shock proteins and transcription
      factors reveals extensive overlap between heat and non-heat stress response
      pathways.
AB  - BACKGROUND: The heat shock response of Arabidopsis thaliana is dependent upon a
      complex regulatory network involving twenty-one known transcription factors and
      four heat shock protein families. It is known that heat shock proteins (Hsps) and
      transcription factors (Hsfs) are involved in cellular response to various forms
      of stress besides heat. However, the role of Hsps and Hsfs under cold and non
      thermal stress conditions is not well understood, and it is unclear which types
      of stress interact least and most strongly with Hsp and Hsf response pathways. To
      address this issue, we have analyzed transcriptional response profiles of
      Arabidopsis Hsfs and Hsps to a range of abiotic and biotic stress treatments
      (heat, cold, osmotic stress, salt, drought, genotoxic stress, ultraviolet light,
      oxidative stress, wounding, and pathogen infection) in both above and below
      ground plant tissues. RESULTS: All stress treatments interact with Hsf and Hsp
      response pathways to varying extents, suggesting considerable cross-talk between
      heat and non-heat stress regulatory networks. In general, Hsf and Hsp expression
      was strongly induced by heat, cold, salt, and osmotic stress, while other types
      of stress exhibited family or tissue-specific response patterns. With respect to
      the Hsp20 protein family, for instance, large expression responses occurred under
      all types of stress, with striking similarity among expression response profiles.
      Several genes belonging to the Hsp20, Hsp70 and Hsp100 families were specifically
      upregulated twelve hours after wounding in root tissue, and exhibited a parallel
      expression response pattern during recovery from heat stress. Among all Hsf and
      Hsp families, large expression responses occurred under ultraviolet-B light
      stress in aerial tissue (shoots) but not subterranean tissue (roots). CONCLUSION:
      Our findings show that Hsf and Hsp family member genes represent an interaction
      point between multiple stress response pathways, and therefore warrant functional
      analysis under conditions apart from heat shock treatment. In addition, our
      analysis revealed several family and tissue-specific heat shock gene expression
      patterns that have not been previously described. These results have implications
      regarding the molecular basis of cross-tolerance in plant species, and raise new
      questions to be pursued in future experimental studies of the Arabidopsis heat
      shock response network.

PMID- 17519033
TI  - BioPP: a tool for web-publication of biological networks.
AB  - BACKGROUND: Cellular processes depend on the function of intracellular molecular
      networks. The curation of the literature relevant to specific biological pathways
      is important for many theoretical and experimental research teams and
      communities. No current tool supports web publication or hosting of user
      developed large scale annotated pathway diagrams. Sharing via web publication is
      needed to allow real-time access to the current literature pathway knowledge
      base, both privately within a research team or publicly among the outside
      research community. Web publication also facilitates team and/or community input
      into the curation process while allowing centralized control of the curation and
      validation process. We have developed new tool to address these needs. Biological
      Pathway Publisher (BioPP) is a software suite for converting CellDesigner Systems
      Biology Markup Language (CD-SBML) formatted pathways into a web viewable format.
      The BioPP suite is available for private use and for depositing knowledge-bases
      into a newly created public repository. RESULTS: BioPP suite is a web-based
      application that allows pathway knowledge-bases stored in CD-SBML to be web
      published with an easily navigated user interface. The BioPP suite consists of
      four interrelated elements: a pathway publisher, an upload web-interface, a
      pathway repository for user-deposited knowledge-bases and a pathway navigator.
      Users have the option to convert their CD-SBML files to HTML for restricted use
      or to allow their knowledge-base to be web-accessible to the scientific
      community. All entities in all knowledge-bases in the repository are linked to
      public database entries as well as to a newly created public wiki which provides
      a discussion forum. CONCLUSION: BioPP tools and the public repository facilitate
      sharing of pathway knowledge-bases and interactive curation for research teams
      and scientific communities. BioPP suite is accessible at
      http://tsb.mssm.edu/pathwayPublisher/broadcast/

PMID- 17519034
TI  - CAG-encoded polyglutamine length polymorphism in the human genome.
AB  - BACKGROUND: Expansion of polyglutamine-encoding CAG trinucleotide repeats has
      been identified as the pathogenic mutation in nine different genes associated
      with neurodegenerative disorders. The majority of individuals clinically
      diagnosed with spinocerebellar ataxia do not have mutations within known disease
      genes, and it is likely that additional ataxias or Huntington disease-like
      disorders will be found to be caused by this common mutational mechanism. We set
      out to determine the length distributions of CAG-polyglutamine tracts for the
      entire human genome in a set of healthy individuals in order to characterize the
      nature of polyglutamine repeat length variation across the human genome, to
      establish the background against which pathogenic repeat expansions can be
      detected, and to prioritize candidate genes for repeat expansion disorders.
      RESULTS: We found that repeats, including those in known disease genes, have
      unique distributions of glutamine tract lengths, as measured by fragment analysis
      of PCR-amplified repeat regions. This emphasizes the need to characterize each
      distribution and avoid making generalizations between loci. The best predictors
      of known disease genes were occurrence of a long CAG-tract uninterrupted by CAA
      codons in their reference genome sequence, and high glutamine tract length
      variance in the normal population. We used these parameters to identify eight
      priority candidate genes for polyglutamine expansion disorders. Twelve CAG
      polyglutamine repeats were invariant and these can likely be excluded as
      candidates. We outline some confusion in the literature about this type of data,
      difficulties in comparing such data between publications, and its application to
      studies of disease prevalence in different populations. Analysis of Gene Ontology
      based functions of CAG-polyglutamine-containing genes provided a visual framework
      for interpretation of these genes' functions. All nine known disease genes were
      involved in DNA-dependent regulation of transcription or in neurogenesis, as were
      all of the well-characterized priority candidate genes. CONCLUSION: This
      publication makes freely available the normal distributions of CAG-polyglutamine
      repeats in the human genome. Using these background distributions, against which
      pathogenic expansions can be identified, we have begun screening for mutations in
      individuals clinically diagnosed with novel forms of spinocerebellar ataxia or
      Huntington disease-like disorders who do not have identified mutations within the
      known disease-associated genes.

PMID- 17519035
TI  - Bladder inflammatory transcriptome in response to tachykinins: neurokinin 1
      receptor-dependent genes and transcription regulatory elements.
AB  - BACKGROUND: Tachykinins (TK), such as substance P, and their neurokinin receptors
      which are ubiquitously expressed in the human urinary tract, represent an
      endogenous system regulating bladder inflammatory, immune responses, and visceral
      hypersensitivity. Increasing evidence correlates alterations in the TK system
      with urinary tract diseases such as neurogenic bladders, outflow obstruction,
      idiopathic detrusor instability, and interstitial cystitis. However, despite
      promising effects in animal models, there seems to be no published clinical study
      showing that NK-receptor antagonists are an effective treatment of pain in
      general or urinary tract disorders, such as detrusor overactivity. In order to
      search for therapeutic targets that could block the tachykinin system, we set
      forth to determine the regulatory network downstream of NK1 receptor activation.
      First, NK1R-dependent transcripts were determined and used to query known
      databases for their respective transcription regulatory elements (TREs). METHODS:
      An expression analysis was performed using urinary bladders isolated from
      sensitized wild type (WT) and NK1R-/- mice that were stimulated with saline, LPS,
      or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent
      genes were selected. PAINT software was used to query TRANSFAC database and to
      retrieve upstream TREs that were confirmed by electrophoretic mobility shift
      assays. RESULTS: The regulatory network of TREs driving NK1R-dependent genes
      presented cRel in a central position driving 22% of all genes, followed by AP-1,
      NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A
      comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as
      a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly
      correlated with 36 transcripts which included several candidates for mediating
      bladder development (FGF) and inflammation (PAR-3, IL-1R, IL-6, alpha-NGF, TSP2).
      In the absence of NK1R, the matrix Nkx2-5_02 had a predominant participation
      driving 8 transcripts, which includes those involved in cancer (EYA1, Trail,
      HSF1, and ELK-1), smooth-to-skeletal muscle trans-differentiation, and Z01, a
      tight-junction protein, expression. Electrophoretic mobility shift assays
      confirmed that, in the mouse urinary bladder, activation of NK1R by substance P
      (SP) induces both NKx-2.5 and NF-kappaB translocations. CONCLUSION: This is the
      first report describing a role for Nkx2.5 in the urinary tract. As Nkx2.5 is the
      unique discriminator of NK1R-modulated inflammation, it can be imagined that in
      the near future, new based therapies selective for controlling Nkx2.5 activity in
      the urinary tract may be used in the treatment in a number of bladder disorders.

PMID- 17519036
TI  - Pediatric malignancies presenting as a possible infectious disease.
AB  - BACKGROUND: The clinical, laboratory, and radiological features of malignancy can
      overlap with those of infection. The purpose of this study was to determine the
      findings in children who were initially thought to have an infectious disease but
      ultimately proved to have a malignancy. METHODS: The database of patients
      diagnosed with a malignancy in the Northern Alberta Children's Cancer Program
      (NACCP) January 1, 1993 to December 31, 2003 was merged with the database of
      inpatients referred to the infectious diseases service at the Stollery Children's
      Hospital and charts were reviewed on all patients referred to the infectious
      diseases consult service prior to the diagnosis of malignancy. RESULTS: An
      infectious diseases consultation for diagnosis was requested in 21 of 561
      patients prior to the confirmation of malignancy, and 3 of these 21 patients had
      both infection and malignancy (leukemia (N = 13), lymphoma (N = 3),
      rhabdomyosarcoma (N = 1), Langerhan's cell histiocytosis (N = 1), fibrous
      histicocytosis (N = 1), ependymoma (N = 1), and neuroblastoma (N = 1). The most
      common reason for infectious diseases consultation was suspected muskuloskeletal
      infection (N = 9). A palpable or radiographically enlarged spleen was noted in 11
      patients (52%). All but 2 patients had abnormal hematologic parameters while an
      elevated lactate dehydrogenase (LDH) occurred in 10 patients (48%). Delay of
      diagnosis because of investigation or therapy for an infectious disease occurred
      in only 2 patients. CONCLUSION: It is not common for treatment of pediatric
      malignancies to be delayed because infection is thought to be the primary
      diagnosis. However, pediatric infectious diseases physicians should consider
      malignancy in the differential diagnosis when they see patients with fever and
      bone pain, unexplained splenomegaly or abnormal complete blood cell counts. Other
      clues may include hepatomegaly or elevated LDH.

PMID- 17519038
TI  - A feature selection approach for identification of signature genes from SAGE
      data.
AB  - BACKGROUND: One goal of gene expression profiling is to identify signature genes
      that robustly distinguish different types or grades of tumors. Several tumor
      classifiers based on expression profiling have been proposed using microarray
      technique. Due to important differences in the probabilistic models of microarray
      and SAGE technologies, it is important to develop suitable techniques to select
      specific genes from SAGE measurements. RESULTS: A new framework to select
      specific genes that distinguish different biological states based on the analysis
      of SAGE data is proposed. The new framework applies the bolstered error for the
      identification of strong genes that separate the biological states in a feature
      space defined by the gene expression of a training set. Credibility intervals
      defined from a probabilistic model of SAGE measurements are used to identify the
      genes that distinguish the different states with more reliability among all gene
      groups selected by the strong genes method. A score taking into account the
      credibility and the bolstered error values in order to rank the groups of
      considered genes is proposed. Results obtained using SAGE data from gliomas are
      presented, thus corroborating the introduced methodology. CONCLUSION: The model
      representing counting data, such as SAGE, provides additional statistical
      information that allows a more robust analysis. The additional statistical
      information provided by the probabilistic model is incorporated in the
      methodology described in the paper. The introduced method is suitable to identify
      signature genes that lead to a good separation of the biological states using
      SAGE and may be adapted for other counting methods such as Massive Parallel
      Signature Sequencing (MPSS) or the recent Sequencing-By-Synthesis (SBS)
      technique. Some of such genes identified by the proposed method may be useful to
      generate classifiers.

PMID- 17519037
TI  - Housekeeping and tissue-specific genes in mouse tissues.
AB  - BACKGROUND: This study aims to characterize the housekeeping and tissue-specific
      genes in 15 mouse tissues by using the serial analysis of gene expression (SAGE)
      strategy which indicates the relative level of expression for each transcript
      matched to the tag. RESULTS: Here, we identified constantly expressed
      housekeeping genes, such as eukaryotic translation elongation factor 2, which is
      expressed in all tissues without significant difference in expression levels.
      Moreover, most of these genes were not regulated by experimental conditions such
      as steroid hormones, adrenalectomy and gonadectomy. In addition, we report
      previously postulated housekeeping genes such as peptidyl-prolyl cis-trans
      isomerase A, glyceraldehyde-3-phosphate dehydrogenase and beta-actin, which are
      expressed in all the tissues, but with significant difference in their expression
      levels. We have also identified genes uniquely detected in each of the 15 tissues
      and other tissues from public databases. CONCLUSION: These identified
      housekeeping genes could represent appropriate controls for RT-PCR and northern
      blot when comparing the expression levels of genes in several tissues. The
      results reveal several tissue-specific genes highly expressed in testis and
      pituitary gland. Furthermore, the main function of tissue-specific genes
      expressed in liver, lung and bone is the cell defence, whereas several keratins
      involved in cell structure function are exclusively detected in skin and vagina.
      The results from this study can be used for example to target a tissue for agent
      delivering by using the promoter of tissue-specific genes. Moreover, this study
      could be used as basis for further researches on physiology and pathology of
      these tissues.

PMID- 17519039
TI  - Factors influencing the spatial extent of mobile source air pollution impacts: a
      meta-analysis.
AB  - BACKGROUND: There has been growing interest among exposure assessors,
      epidemiologists, and policymakers in the concept of "hot spots", or more broadly,
      the "spatial extent" of impacts from traffic-related air pollutants. This review
      attempts to quantitatively synthesize findings about the spatial extent under
      various circumstances. METHODS: We include both the peer-reviewed literature and
      government reports, and focus on four significant air pollutants: carbon
      monoxide, benzene, nitrogen oxides, and particulate matter (including both
      ultrafine particle counts and fine particle mass). From the identified studies,
      we extracted information about significant factors that would be hypothesized to
      influence the spatial extent within the study, such as the study type (e.g.,
      monitoring, air dispersion modeling, GIS-based epidemiological studies), focus on
      concentrations or health risks, pollutant under study, background concentration,
      emission rate, and meteorological factors, as well as the study's implicit or
      explicit definition of spatial extent. We supplement this meta-analysis with
      results from some illustrative atmospheric dispersion modeling. RESULTS: We found
      that pollutant characteristics and background concentrations best explained
      variability in previously published spatial extent estimates, with a modifying
      influence of local meteorology, once some extreme values based on health risk
      estimates were removed from the analysis. As hypothesized, inert pollutants with
      high background concentrations had the largest spatial extent (often
      demonstrating no significant gradient), and pollutants formed in near-source
      chemical reactions (e.g., nitrogen dioxide) had a larger spatial extent than
      pollutants depleted in near-source chemical reactions or removed through
      coagulation processes (e.g., nitrogen oxide and ultrafine particles). Our
      illustrative dispersion model illustrated the complex interplay of spatial extent
      definitions, emission rates, background concentrations, and meteorological
      conditions on spatial extent estimates even for non-reactive pollutants. Our
      findings indicate that, provided that a health risk threshold is not imposed, the
      spatial extent of impact for mobile sources reviewed in this study is on the
      order of 100-400 m for elemental carbon or particulate matter mass concentration
      (excluding background concentration), 200-500 m for nitrogen dioxide and 100-300
      m for ultrafine particle counts. CONCLUSION: First, to allow for meaningful
      comparisons across studies, it is important to state the definition of spatial
      extent explicitly, including the comparison method, threshold values, and whether
      background concentration is included. Second, the observation that the spatial
      extent is generally within a few hundred meters for highway or city roads
      demonstrates the need for high resolution modeling near the source. Finally, our
      findings emphasize that policymakers should be able to develop reasonable
      estimates of the "zone of influence" of mobile sources, provided that they can
      clarify the pollutant of concern, the general site characteristics, and the
      underlying definition of spatial extent that they wish to utilize.

PMID- 17519040
TI  - Adherence to physiotherapy clinical guideline acute ankle injury and determinants
      of adherence: a cohort study.
AB  - BACKGROUND: Clinical guidelines are considered important instruments to improve
      quality in health care. In physiotherapy, insight in adherence to guidelines is
      limited. Knowledge of adherence is important to identify barriers and to enhance
      implementation. Purpose of this study is to investigate the ability to adherence
      to recommendations of the guideline Acute ankle injury, and to identify patient
      characteristics that determine adherence to the guideline. METHODS: Twenty-two
      physiotherapists collected data of 174 patients in a prospective cohort study, in
      which the course of treatment was systematically registered. Indicators were used
      to investigate adherence to recommendations. Patient characteristics were used to
      identify prognostic factors that may determine adherence to the guideline.
      Correlation between patient characteristics and adherence to outcome-indicators
      (treatment sessions, functioning of patient, accomplished goals) was calculated
      using univariate logistic regression. To calculate explained variance of combined
      patient characteristics, multivariate analysis was performed. RESULTS: Adherence
      to individual recommendations varied from 71% to 100%. In 99 patients (57%) the
      physiotherapists showed adherence to all indicators. Adherence to preset maximum
      of six treatment sessions for patients with severe ankle injury was 81% (132
      patients). The odds to receive more than six sessions were statistically
      significant for three patient characteristics: females (OR:3.89; 95%CI: 1.41
      10.72), recurrent sprain (OR: 6.90; 95%CI: 2.34 - 20.37), co-morbidity (OR:
      25.92; 95% CI: 6.79 - 98.93). All factors together explained 40% of the variance.
      Inclusion of physiotherapist characteristics in the regression model showed that
      work-experience reduced the odds to receive more than six sessions (OR: 0.2;
      95%CI: 0.06 - 0.77), and increased explained variance to 45%. CONCLUSION:
      Adherence to the clinical guideline Acute ankle sprain showed that the guideline
      is applicable in daily practice. Adherence to the guideline, even in a group of
      physiotherapists familiar with the guideline, showed possibilities for
      improvement. The necessity to exceed the expected number of treatment sessions
      may be explained by co-morbidity and recurrent sprains. It is not clear why
      female patients were treated with more sessions. Experience of the
      physiotherapist reduced the number of treatment sessions. Quality indicators may
      be used for audit and feedback as part of the implementation strategy.

PMID- 17519041
TI  - Estimating the annotation error rate of curated GO database sequence annotations.
AB  - BACKGROUND: Annotations that describe the function of sequences are enormously
      important to researchers during laboratory investigations and when making
      computational inferences. However, there has been little investigation into the
      data quality of sequence function annotations. Here we have developed a new
      method of estimating the error rate of curated sequence annotations, and applied
      this to the Gene Ontology (GO) sequence database (GOSeqLite). This method
      involved artificially adding errors to sequence annotations at known rates, and
      used regression to model the impact on the precision of annotations based on
      BLAST matched sequences. RESULTS: We estimated the error rate of curated GO
      sequence annotations in the GOSeqLite database (March 2006) at between 28% and
      30%. Annotations made without use of sequence similarity based methods (non-ISS)
      had an estimated error rate of between 13% and 18%. Annotations made with the use
      of sequence similarity methodology (ISS) had an estimated error rate of 49%.
      CONCLUSION: While the overall error rate is reasonably low, it would be prudent
      to treat all ISS annotations with caution. Electronic annotators that use ISS
      annotations as the basis of predictions are likely to have higher false
      prediction rates, and for this reason designers of these systems should consider
      avoiding ISS annotations where possible. Electronic annotators that use ISS
      annotations to make predictions should be viewed sceptically. We recommend that
      curators thoroughly review ISS annotations before accepting them as valid.
      Overall, users of curated sequence annotations from the GO database should feel
      assured that they are using a comparatively high quality source of information.

PMID- 17519042
TI  - HYBRIDdb: a database of hybrid genes in the human genome.
AB  - BACKGROUND: Hybrid genes are candidate risk factors for human tumors by inducing
      mutation, translocation, inversion, or rearrangement of genes. The occurrence of
      hybrid genes may also have given rise to new transcripts during hominid
      evolution. DESCRIPTION: HYBRIDdb is a database of hybrid genes in humans. This
      system encompasses the bioinformatics analysis of mRNA, EST, cDNA, and genomic
      DNA sequences in the INDC databases, and can be used to identify hybrid genes. We
      searched for hybrid genes among the 28,171 genes listed in the NCBI database, and
      analyzed their structural patterns in the human genome. The 2,344 gene pairs were
      detected as hybrid forms of transcriptional products. We classified the hybrid
      genes into two groups: chromosomal-mediated translocation fusion transcripts and
      transcription-mediated fusion transcripts. CONCLUSION: The HYBRIDdb database will
      provide genome scientists with insight into potential roles for hybrid genes in
      human evolution and disease.

PMID- 17519043
TI  - Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1
      response in a mouse hepatic cancer model.
AB  - BACKGROUND: The novel cytokine, interleukin (IL)-18, is a strong interferon-gamma
      inducer and costimulatory factor in Th1 cell activation. IL-18 triggers IFN-gamma
      production and enhances cytolytic activity in both T and NK cells. However, the
      exact mechanism of antitumor action of IL-18 remains to be clarified. To
      determine the effects of IL-18 plasmid DNA on hepatic cancer in mice, CT26 murine
      colon adenocarcinoma cells were established in mouse liver. METHODS: Plasmid
      vectors encoding IL-18 were transferred directly into the liver 7 days after
      tumor injection to restrict IL-18 expression within the tumor site. The IL-18
      protein level was increased in the liver 4 days after plasmid injection, and a
      marked antitumoral effect was observed at day 7. Antitumor effects were evaluated
      by measuring tumor regression, immune cell population, and IFN-gamma production.
      RESULTS: The IL-18 plasmid controlled the growth of hepatic tumors and
      proliferation of splenic immune cells. Moreover, treatment of CT26 tumors with
      the IL-18 plasmid significantly enhanced the population of the effector T and NK
      cells in the spleen and peripheral blood. In spleen, the population of
      CD4+CD62Low cells was augmented in response to IL-18 on day 7. These results are
      consistent with the increase in CD4+ T cells secreting IFN-gamma, but not CD8+ T
      cells. The marked reduction of tumor growth in tumor-bearing mice was associated
      with the maintenance of IFN-gamma production in spleen in response to IL-18.
      These antitumoral effects were maintained until 14 days after plasmid injection.
      CONCLUSION: Our results suggest that direct plasmid DNA transfer of IL-18 with no
      accompanying reagents to augment transfection efficiency may be useful in tumor
      immunotherapy.

PMID- 17519044
TI  - Epidemiology and patterns of care for invasive breast carcinoma at a community
      hospital in Southern India.
AB  - BACKGROUND: Breast cancer incidence in India is on rise. We report
      epidemiological, clinical and survival patterns of breast cancer patients from
      community perspective. METHODS: All breast cancer patients treated at this
      hospital from July 2000 to July 2005 were included. All had cytological or
      histological confirmation of breast cancer. TNM guidelines for staging and
      Immunohistochemistry to assess the receptor status were used. Either lumpectomy
      with axillary lymph node dissection or Modified radical mastectomy (MRM) was done
      for operable breast cancer, followed by 6 cycles of adjuvant chemotherapy with
      FAC or CMF regimens to patients with pT >1 cm or lymph node positive or estrogen
      receptor negative and radiotherapy to patients after breast conservation surgery,
      pT size > 5 cm, 4 or more positive nodes and stage IIIB disease. Patients with
      positive Estrogen receptor or Progesterone receptor were advised Tamoxifene 20 mg
      per day for 3 years. Descriptive analysis was performed. Independent T test and
      Chi-square test were used. Overall survival time was computed by Kaplan - Meier
      method. RESULTS: Of 1488 cancer patients, 122 (8.2%) had breast cancer. Of 122
      patients, 96.7% had invasive breast carcinoma and 3.3% had sarcoma. 94% came from
      the rural and semi urban areas. Premenopausal women were 27%. The median age was
      50 years. Stage I-6.8%, II-45.8%, III-22%, IV-6.8%, Bilateral breast cancer -
      2.5%. The mean pT size was 3.9 cm. ER and PR were positive in 31.6% and 28.1%
      respectively. MRM was done in 93.8%, while 6.3% patients underwent breast
      conservation surgery. The mean of the lymph nodes dissected were 3. CMF and FAC
      regimens were used in 48.8% and 51.2% of patients respectively. FAC group were
      younger than the CMF group (43.6 yr vs. 54 yrs, P = 0.000). Toxicities were more
      in FAC than CMF group, alopecia (100% vs. 26.2%), grade2 or more emesis (31.8%
      vs. 9.2%), grade2 or more fatigue (40.9% vs.19%), anemia (43.1% vs. 16.6%).
      Median Survival for the cohort was 50.8 months. ER positive patients had better
      median survival (P = 0.05). CONCLUSION: MRM was the most frequent surgical
      option. CMF and FAC showed equivalent survival. FAC chemotherapy was more toxic
      than CMF. ER positive tumors have superior survival. Overall 3 year survival was
      70 percent.

PMID- 17519045
TI  - A hydrogen-bonded channel structure formed by a complex of uracil and melamine.
AB  - The structure of a 1:1 complex of uracil and melamine obtained by
      cocrystallization has been investigated. The structure involves hydrogen bonded
      layers with apertures stacked along the a and b directions giving rise to
      channels, unlike the complex of cyanuric acid with melamine.

PMID- 17519047
TI  - Validation of a diet history questionnaire for use with Costa Rican adults.
AB  - OBJECTIVE: To validate a diet history questionnaire (DHQ) using a weighed food
      record (WFR) as the standard method in the estimation of food consumption and
      nutrient intake in a group of adults. DESIGN: WFR: all foods consumed by subjects
      during 7 consecutive days were weighed and recorded by nutrition students. Two
      DHQ interviews were carried out on days 1 (first diet history questionnaire,
      DHQ1) and 28 (second diet history questionnaire, DHQ2). SETTING: Costa Rica.
      SUBJECTS: Sixty adults: 30 men and 30 women; 30 living in urban and 30 in rural
      areas. RESULTS: In comparison to the WFR, the DHQ1 gave statistically significant
      higher estimates of the mean intake of 19 nutrients for men and of three
      nutrients for women. The uncorrected correlation coefficients for nutrient intake
      according to both methods ranged from 0.40 to 0.83 for males and from 0.22 to
      0.62 for females. Percentage of subjects classified in the same quartiles of
      nutrient intake according to each method ranged from 33.3% to 63.3% for males and
      from 23.3% to 53.3% for females. Misclassification in extreme quartiles ranged
      from 0% to 13.3% for both sexes. The mean food group consumption, according to
      the DHQ1, when compared with the WFR, gave statistically significant differences
      for three of the 18 food groups for men and for two groups in the case of women.
      The two applications of the DHQ gave similar results. CONCLUSION: Validation of a
      DHQ using a WFR as the standard method gave results that compare favourably with
      those reported by other authors. This study found important differences in the
      response of men and women to the DHQ: among men, the estimates of mean nutrient
      intake from DHQ1 were significantly greater than those of the WFR, while in the
      case of women, the mean nutrient intake estimates from both methods were not
      significantly different. There was a higher degree of correlation between the
      DHQ1 and the WFR mean nutrient intakes among men than among women. The DHQ showed
      good reproducibility.

PMID- 17519046
TI  - The N-terminus and alpha-5, alpha-6 helices of the pro-apoptotic protein Bax,
      modulate functional interactions with the anti-apoptotic protein Bcl-xL.
AB  - BACKGROUND: Bcl-2 family proteins are key regulators of mitochondrial integrity
      and comprise both pro- and anti-apoptotic proteins. Bax a pro-apoptotic member
      localizes as monomers in the cytosol of healthy cells and accumulates as
      oligomers in mitochondria of apoptotic cells. The Bcl-2 homology-3 (BH3) domain
      regulates interactions within the family, but regions other than BH3 are also
      critical for Bax function. Thus, the N-terminus has been variously implicated in
      targeting to mitochondria, interactions with BH3-only proteins as well as
      conformational changes linked to Bax activation. The transmembrane (TM) domains
      (alpha5-alpha6 helices in the core and alpha9 helix in the C-terminus) in Bax are
      implicated in localization to mitochondria and triggering cytotoxicity. Here we
      have investigated N-terminus modulation of TM function in the context of
      regulation by the anti-apoptotic protein Bcl-xL. RESULTS: Deletion of 29 amino
      acids in the Bax N-terminus (Bax 30-192) caused constitutive accumulation at
      mitochondria and triggered high levels of cytotoxicity, not inhibited by Bcl-xL.
      Removal of the TM domains (Bax 30-105) abrogated mitochondrial localization but
      resulted in Bcl-xL regulated activation of endogenous Bax and Bax-Bak dependent
      apoptosis. Inclusion of the alpha5-alpha6 helices/TMI domain (Bax 30-146)
      phenocopied Bax 30-192 as it restored mitochondrial localization, Bcl-xL
      independent cytotoxicity and was not dependent on endogenous Bax-Bak. Inhibition
      of function and localization by Bcl-xL was restored in Bax 1-146, which included
      the TM1 domain. Regardless of regulation by Bcl-xL, all N-terminal deleted
      constructs immunoprecipitated Bcl-xLand converged on caspase-9 dependent
      apoptosis consistent with mitochondrial involvement in the apoptotic cascade. Sub
      optimal sequence alignments of Bax and Bcl-xL indicated a sequence similarity
      between the alpha5-alpha6 helices of Bax and Bcl-xL. Alanine substitutions of
      three residues (T14A-S15A-S16A) in the N-terminus (Bax-Ala3) attenuated
      regulation by the serine-threonine kinase Akt/PKB but not by Bcl-xL indicative of
      distinct regulatory mechanisms. CONCLUSION: Collectively, the analysis of Bax
      deletion constructs indicates that the N-terminus drives conformational changes
      facilitating inhibition of cytotoxicity by Bcl-xL. We speculate that the TM1
      helices may serve as 'structural antagonists' for BH3-Bcl-xL interactions, with
      this function being regulated by the N-terminus in the intact protein.

PMID- 17519048
TI  - Iron supplementation compliance among pregnant women in Bicol, Philippines.
AB  - OBJECTIVE: To quantify factors influencing iron supplementation compliance and
      haemoglobin (Hb) concentrations among pregnant women participating in an iron
      supplementation programme under routine field conditions. DESIGN: Cross-sectional
      interviews and Hb measurements. SETTINGS: Albay and Sorsogon provinces, Bicol,
      Philippines. SUBJECTS: Three hundred and forty-six pregnant women receiving iron
      supplements via the Philippine iron supplementation programme. RESULTS: Women had
      a mean Hb concentration of 10.75 +/- 1.43 g dl-1, and 56.4% were anaemic (Hb <
      11.0 g dl-1). On average, the first prenatal visit occurred at nearly 4 months
      (3.80 +/- 1.56). The ratio of visits to number of months pregnant was 0.51 +/-
      0.24. Self-reported consumption of pills received was 85% (0.85 +/- 0.23),
      although pill counts suggested that consumption was 70% (0.70 +/- 0.35). Using
      multiple regression, an earlier first prenatal visit and greater self-reported
      compliance were positively associated with Hb concentrations. Additionally,
      perceived health benefits from taking the supplements and higher health programme
      knowledge were positively associated with pill consumption, while experiencing
      side-effects and disliking the taste of the supplements were associated with
      lower pill consumption. A greater number of living children was negatively
      associated with the frequency of prenatal visits. The number of children was also
      directly negatively associated with Hb concentrations. CONCLUSIONS: Compliance
      was positively related to Hb concentrations. Several factors associated with
      greater compliance were identified, including marital status, number of children,
      health programme knowledge, side-effects, perceived health benefits, and dislike
      of taste. Some of these factors may serve as avenues for interventions to
      increase compliance, and ultimately Hb concentrations.

PMID- 17519049
TI  - Comparison of effects of preoperatively administered lornoxicam and tenoxicam on
      morphine consumption after laparoscopic cholecystectomy.
AB  - BACKGROUND AND OBJECTIVE: The efficacy, tolerability and the morphine-sparing
      effects of lornoxicam were compared with those of tenoxicam when used
      preoperatively in patients undergoing laparoscopic cholecystectomy. METHODS: In
      this prospective, double-blind study, 60 ASA I-II patients undergoing
      laparoscopic cholecystectomy were randomized equally to receive intravenous
      tenoxicam 40 mg (Group T) or lornoxicam 16 mg (Group L), preemptively. Three
      patients withdrew from the study, so 57 patients were included in the analysis.
      In the postoperative period, the first morphine demand times, pain scores, side
      effects and cumulative morphine consumptions were evaluated during the first 24
      h. RESULTS: The patient characteristics data and the duration of surgery were
      similar between two groups, except for body weights (P = 0.002). The first
      morphine demand time was significantly longer in Group L (P = 0.037), but the
      pain levels did not differ. The mean pain scores were higher in Group T in the 15
      min (P = 0.036), 1 h (P = 0.020), 2 h (P = 0.001) and 4 h (P = 0.0042) after
      extubation. A statistically significant difference between two groups was found
      in calculated cumulative morphine consumptions per kilogram in the 15 min (P =
      0.037), 30 min (P = 0.016), and 1 h (P = 0.004) and 2 h (P = 0.013) between two
      groups. There was no difference in the severity of nausea but 13 patients in
      Group T and five patients in Group L had vomiting (P = 0.018). Patient
      satisfaction was similar in the two groups. CONCLUSIONS: Preoperatively
      administered lornoxicam 16 mg significantly prolonged the first morphine demand
      time, reduced postoperative morphine consumption during the first 4 h and caused
      significantly fewer adverse effects when compared with tenoxicam after
      laparoscopic cholecystectomy.

PMID- 17519050
TI  - The need for a global telemedicine society.

PMID- 17519051
TI  - Low-bandwidth teleconsultations for patients with complex congenital heart
      diseases.
AB  - We have reviewed our experience with a low-bandwidth paediatric telecardiology
      link (using ISDN at 128 kbit/s) between a tertiary centre in Belgrade and a
      tertiary centre in London. Over a two-year period, 12 videoconferences were held,
      during which 40 case histories of 38 patients were presented from Belgrade. The
      patients were aged 7 days to 20 years, and most of them had complex congenital
      heart defects. Changes in diagnosis and/or therapy occurred in 21 cases.
      Clinically relevant changes in diagnosis occurred in 2/40 cases (5%). In 12
      cases, there were slight differences in opinion which resulted in minor changes
      in therapy for 9 of the patients. In another 9 patients, major changes in therapy
      occurred. There were no major problems with the quality of image and sound in any
      of the videoconferences. Our experience suggests that when there are experienced
      paediatric cardiologists at both ends of the connection, transmission via a
      single ISDN line is safe and accurate.

PMID- 17519052
TI  - A feasibility study of an Internet-based telemedicine system for consultation in
      an ophthalmic emergency room.
AB  - We examined the feasibility of a low-bandwidth, Internet-based tele-ophthalmology
      system for consultation in an ophthalmic emergency room. Forty-nine patients (98
      eyes) with complicated cases were seen during night shifts in the ophthalmic
      emergency room. Ocular images were taken using a slit-lamp connected to a video
      camera, processed and transmitted to a senior physician by email. A telephone was
      used for real-time audio communication. Each case was re-examined by the same
      senior physician the following day. The time needed to capture and to process the
      images was 5 min (SD 2). Each case was given a feasibility score (0-100%), which
      was defined as the contribution made by the transmitted images in presenting
      clinical details which could not have been described verbally. High feasibility
      scores (mean scores ranging from 85 to 90) were found for the following images:
      ocular surface, anterior chamber, anterior chamber angle, pupils, lens, optic
      nerve and macula. In contrast, images of vitreous and peripheral retina received
      low feasibility scores (mean score 65). There was 100% agreement between the
      diagnosis made during consultation and the on-site examination made by the senior
      ophthalmologist later on. Ninety-eight percent of the patients stated that they
      would prefer being examined under the telemedicine system on their next emergency
      room visit, rather than the traditional resident on-site examination.

PMID- 17519053
TI  - Videoconferencing in child and adolescent psychiatry in Finland--an inadequately
      exploited resource.
AB  - To assess the current role of videoconferencing and the purposes for which it has
      been used in child and adolescent psychiatry in Finland, we sent a 16-item
      questionnaire to all providers of child and adolescent psychiatry services in
      specialised health care in Finland, i.e. the 42 child and adolescent units in 21
      hospital districts. All service providers responded. The responses to both open
      ended and structured questions were analysed manually and classified
      quantitatively and qualitatively. Use of videoconferencing was reported by 16 of
      the 21 hospital districts in Finland. Videoconferencing had been used for more
      than 5.5 years in only three hospital districts, for 3-5 years in 14 units and
      for 1-3 years in six units. Videoconferencing was used for clinical work in 12
      and for distance education in another 12 hospital districts. Videoconferencing
      was used weekly for clinical work and for supervision by two districts; it was
      used for education by three districts. Although the workers' experiences of and
      attitudes towards videoconferencing were favourable, it has not been widely used
      in child and adolescent psychiatry. The implementation of videoconferencing seems
      to depend more on the activity of service providers than on the number of people
      involved.

PMID- 17519054
TI  - Use of videoconferencing in Norwegian psychiatry.
AB  - We conducted a national survey about access to and use of videoconferencing in
      Norwegian mental health care. A questionnaire was mailed to 300 institutions,
      with 113 returned (38%). Attitudes towards videoconferencing were positive. 58 of
      the respondents had access to videoconferencing equipment. 51 institutions had
      used videoconferencing in the previous year. Geographical and climatic factors
      and travel-related strain were predictors of access. Videoconferencing was mostly
      used for meetings, supervision and lectures, and to a lesser degree was used
      clinically, with the patient present. 90% of the institutions had experienced
      videoconferencing as useful. Lack of videoconferencing equipment in collaborating
      institutions was an inhibiting factor for use. There is a gap between the
      potential of videoconferencing and its actual utilization in Norway's mental
      health sector.

PMID- 17519055
TI  - Cardiology grand rounds: effect of videoconferencing on educational value.
AB  - We studied four cardiology grand rounds transmitted by videoconference from a
      tertiary care centre to four other hospitals in eastern Canada. We collected data
      with evaluation questionnaires and by video recording participants at the
      receiving-site and the presentation they received from the presenting site.
      Receiving-site participants (n=20) rated their satisfaction with all domains
      significantly lower than did presenting-site participants (n=49). The greatest
      difference in ratings was in the ability to see slides (receiving sites 2.6/5,
      presenting site 4.6/5). Review of video recordings revealed that slides showing
      material copied from print sources was difficult to read at receiving sites.
      While 56% of discussion time was devoted to questions from receiving sites,
      participants there rated their ability to participate in discussion lower than
      those at the presenting site (3.9/5 vs 4.4/5). This may be because some parts of
      the discussion from the presenting site were not transmitted. Receiving-site
      participants rated the educational value of the rounds lower than their
      presenting-site colleagues (3.9/5 vs 4.4/5) but answered a similar percentage of
      knowledge questions correctly (85 vs 89%).

PMID- 17519056
TI  - A randomized trial of telepsychiatry for post-traumatic stress disorder.
AB  - We compared the efficacy of telepsychiatry and same-room treatment of combat
      related post-traumatic stress disorder (PTSD) using cognitive behavioural therapy
      in 14 weekly, 90-min treatment sessions. Of 97 patients referred for study
      participation, 38 were randomized (17 into telepsychiatry, 21 into same-room),
      and approximately 25 (the number differed by instrument) had at least one post
      baseline assessment. Measures of clinical and process outcomes were examined. No
      group differences were found on clinical outcomes at three-month follow-up.
      Satisfaction with treatment ratings was similar in both groups, with 'strong
      satisfaction' indicated by veterans in both modalities. Attendance and drop-out
      were similar in the two groups. The same-room group reported more comfort in
      talking with their therapist at post-treatment and had better treatment
      adherence. The results provide preliminary support for the use of telepsychiatry
      in the treatment of PTSD to improve access to care.

PMID- 17519057
TI  - Qualitative and quantitative assessment of video transmitted by DVTS (digital
      video transport system) in surgical telemedicine.
AB  - Real-time video pictures can be transmitted inexpensively via a broadband
      connection using the DVTS (digital video transport system). However, the
      degradation of video pictures transmitted by DVTS has not been sufficiently
      evaluated. We examined the application of DVTS to remote consultation by using
      images of laparoscopic and endoscopic surgeries. A subjective assessment by the
      double stimulus continuous quality scale (DSCQS) method of the transmitted video
      pictures was carried out by eight doctors. Three of the four video recordings
      were assessed as being transmitted with no degradation in quality. None of the
      doctors noticed any degradation in the images due to encryption by the VPN
      (virtual private network) system. We also used an automatic picture quality
      assessment system to make an objective assessment of the same images. The
      objective DSCQS values were similar to the subjective ones. We conclude that
      although the quality of video pictures transmitted by the DVTS was slightly
      reduced, they were useful for clinical purposes. Encryption with a VPN did not
      degrade image quality.

PMID- 17519058
TI  - Nuclear medical expertise delivered by telemedicine in a 'dirty bomb' exercise.
AB  - Management of victims in a 'dirty bomb' incident requires communication between
      the physicians directly involved and experts in radiation medicine. Telemedicine
      is an excellent tool to support doctors--who may not have specific training in
      radiation medicine--in handling radiation casualties. We have successfully used
      telemedicine in an exercise of the Federal Police in Germany. Experts in
      radiation medicine were provided by the Bundeswehr Institute of Radiobiology.
      Simple PC-based videoconferencing equipment was used with a 128 kbit/s ISDN line.
      To facilitate a standardized approach, a new questionnaire for radiation
      accidents was developed and tested during the exercise. A special camera was used
      for capturing skin images. Advice for patient treatment and strategies for
      safeguarding personnel and the environment during the exercise was provided
      almost immediately.

PMID- 17519059
TI  - A national telehealth nursing research agenda.

PMID- 17519060
TI  - Inaugural paediatric telehealth colloquium.

PMID- 17519062
TI  - Perindopril arginine: benefits of a new salt of the ACE inhibitor perindopril.
AB  - BACKGROUND: The efficacy of the angiotensin-converting enzyme (ACE) inhibitor
      perindopril in the treatment of hypertension, stable coronary artery disease, and
      heart failure is well established. The reduced stability of the current salt,
      perindopril-tert-butylamine, in extreme climatic conditions has prompted research
      into more stable compounds. This article presents stability and bioequivalence
      results for a new L-arginine salt of perindopril. METHODS: Drug stability studies
      were performed on nonsalified perindopril, perindopril-tert-butylamine, and
      perindopril arginine in closed and open containers. The bioequivalence of
      perindopril arginine was tested in 36 healthy male volunteers in an open-label,
      randomized, two-period, crossover pharmacokinetic study. A consumer study was
      carried out in 120 patients to assess preference for a simplified packaging using
      a high-density polyethylene canister designed for distribution to all climatic
      zones. RESULTS AND DISCUSSION: Perindopril arginine is 50% more stable than
      perindopril-tert-butylamine, which increases the shelf life from 2 to 3 years. At
      the revised dosage (perindopril arginine 5-10 mg/day corresponds to perindopril
      tert-butylamine 4-8 mg/day), the new salt is equivalent in terms of
      pharmacokinetics, efficacy, safety, and acceptability. The consumer studies
      indicate a preference for the new packaging, with 62% of patients nominating the
      canister as better than the blister packs. CONCLUSION: The new perindopril
      arginine salt is equivalent to perindopril-tert-butylamine and more stable, and
      can be distributed to climatic zones III and IV without the need for specific
      packaging. The patient preference for the new packaging could have positive
      implications for compliance.

PMID- 17519063
TI  - A retrospective analysis of low-field strength magnetic resonance imaging and the
      management of patients with rheumatoid arthritis.
AB  - OBJECTIVE: To assess how in-office magnetic resonance imaging (MRI) scans of the
      hand/wrist or feet are utilized in a rheumatology practice to make clinical
      evaluations regarding therapeutic options for rheumatoid arthritis (RA) patients.
      METHODS: In a large clinical practice, a retrospective review was conducted on
      the first 300 RA patients who had office-based MRI scans at baseline. Information
      was collected on demographics, baseline therapy, and whether any change in
      therapy occurred at the time of the MRI scans. MR images of the affected wrist
      were obtained with a low-field strength dedicated extremity unit. RESULTS: Of the
      300 patients, 99 patients (33%) had MRIs that exhibited signs of erosions, joint
      space narrowing, or bone edema. These patients were classified as MRI-positive.
      The remaining 201 patients (67%) were classified as MRI-negative. A substantial
      majority (85%) of MRI-positive patients received a change in their therapeutic
      regimen, compared with only 9.5% of the MRI-negative patients (p < 0.001). In the
      84 MRI-positive patients who had their therapy changed, 65% received a new
      prescription for a biologic or an increase in the dose of their existing biologic
      and 34% of the MRI-positive patients received a DMARD. In the 19 MRI-negative
      patients with a therapeutic change, 11% received a biologic agent and 88%
      received a DMARD. The major limitation of this study is that it was a
      retrospective analysis and the assessments of MRI findings were qualitative.
      CONCLUSION: In this large population of RA patients, there was an association
      between MRI detection of joint space narrowing, erosions, and/or bone edema and
      change in therapeutic management.

PMID- 17519064
TI  - Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable
      haemoglobin in patients with CKD on dialysis: once monthly administration.
AB  - AIMS: This Phase II study aimed to determine the optimal dose and administration
      schedule of continuous erythropoietin receptor activator (C.E.R.A.) given
      subcutaneously (s.c.) in patients receiving dialysis converting directly from
      s.c. epoetin therapy 1-3 times/week. An extension phase examined long-term safety
      and efficacy. METHODS: Patients were assigned to one of three C.E.R.A. dose
      groups determined by multiplying the previous weekly dose of epoetin by one of
      three ratios (0.4/150, 0.8/150, 1.2/150 for groups A, B and C, respectively).
      Within each group, patients were randomized to once weekly (QW), once every 3
      weeks (Q3W) and once monthly (Q4W) schedules. Dose adjustments were not permitted
      for the first 6 weeks. The core study period was 19 weeks (21 weeks in the Q4W
      cohorts). Patients could enter a 12-month extension period at the same schedule,
      aiming to maintain haemoglobin (Hb) at 11-12 g/dL. RESULTS: 137 patients entered
      the core period, and 62 continued into the extension period. A dose-dependent
      relationship was seen in the primary efficacy variable, change in Hb standardized
      to a 6 week period (p < 0.0001), but effect was independent of schedule. Hb
      levels were maintained throughout the study, with few dose changes. C.E.R.A. was
      generally well tolerated and the most frequent adverse event was hypotension.
      CONCLUSION: The results suggest that s.c. C.E.R.A. at up to once monthly
      intervals provides stable maintenance of Hb levels in dialysis patients
      converting directly from epoetin 1-3 times/week. Achieving tight Hb control with
      few dose adjustments at extended administration intervals may offer health
      benefits and improvements in resource management.

PMID- 17519065
TI  - Efficacy and safety evaluation of once-daily OROS hydromorphone in patients with
      chronic low back pain: a pilot open-label study (DO-127).
AB  - OBJECTIVE: To evaluate the safety, tolerability, and efficacy of once-daily
      osmotic controlled-release oral delivery system (OROS) hydromorphone in patients
      with chronic low back pain of moderate-to-severe intensity. RESEARCH DESIGN AND
      METHODS: This was a 6-week, multicenter, nonrandomized, noncomparative, open
      label, repeat-dose study of chronic (> or = 6 weeks) low back pain. The study
      comprised three periods: prior opioid stabilization (2-7 days); OROS
      hydromorphone conversion, titration, and stabilization (3-14 days); and OROS
      hydromorphone maintenance (28 days). Patients were evaluated weekly. Baseline
      pain assessment was performed at the end of prior opioid stabilization. For pain
      relief rating, endpoint was defined as the mean pain relief score from the last 2
      nonmissing days before study termination. For other assessments, endpoint was
      defined as the last post-baseline evaluation. RESULTS: Of the 207 patients who
      received the study drug, 131 completed the trial. Scores (mean +/- SD) for Brief
      Pain Inventory 'worst pain in the last 24 hours' decreased significantly from
      baseline to endpoint (-0.8 +/- 2.06, p < 0.0001). The proportions of patients and
      investigators rating the global effectiveness as good, very good, or excellent
      increased from 31.6% at baseline while patients were on prior opioids to 63.2% at
      endpoint while patients received OROS hydromorphone, and from 29.8% at baseline
      while patients were on prior opioids to 65.8% at endpoint while patients received
      OROS hydromorphone, respectively. Daily pain relief ratings also increased
      significantly (+0.26 +/- 1.084, p = 0.0008). Significant improvements in health
      related quality of life and sleep problems were observed. Adverse events were
      mild to moderate in severity; the most common of these were constipation, nausea,
      headache, and somnolence. The limitations of this study include its pilot-type
      design and the lack of comparison of OROS hydromorphone with a placebo or another
      drug. Additional comparative and longer-term studies are needed to confirm these
      findings. CONCLUSIONS: OROS hydromorphone may be an effective treatment for
      chronic low back pain of moderate-to-severe intensity. Adverse events were
      typical of those associated with opioid therapy.

PMID- 17519066
TI  - A phase I clinical and pharmacokinetic study of tipifarnib in combination with
      docetaxel in patients with advanced solid malignancies.
AB  - PURPOSE: This phase I study assessed the maximum tolerated doses (MTDs), safety,
      pharmacokinetics, and efficacy of combined tipifarnib and docetaxel treatment in
      patients with advanced solid malignancies. EXPERIMENTAL DESIGN: The study
      protocol was sensitive to myelosuppression, as both drugs have been associated
      with this adverse event. Due to myelosuppression incidence, and in order to
      determine the MTD of docetaxel, multiple treatment regimens were employed.
      Tipifarnib was administered orally at 200 or 300 mg, twice daily (BID) for 21
      days, 14 days, or 7 days for multiple 21-day cycles; intravenous (i.v.) docetaxel
      was administered on day 1 of each cycle at 60, 75, or 85 mg/m2. RESULTS: A total
      of 36 patients entered into the study. For each drug, MTDs were identified
      (tipifarnib: 300 mg BID for 14 days with 60 mg/m2 docetaxel; tipifarnib: 200 mg
      BID for 14 days with 75 mg/m2 docetaxel). The major dose-limiting toxicity was
      myelosuppression, particularly febrile neutropenia (44%). Mutual pharmacokinetic
      interactions (the effect of docetaxel on tipifarnib pharmacokinetics and the
      effect of tipifarnib on docetaxel pharmacokinetics) were not evident, as maximum
      plasma concentration (Cmax) and the area under the serum concentration-time curve
      (AUC) values of both tipifarnib and docetaxel were similar (p > or = 0.43)
      whether the two drugs were concomitantly administered or not. Seven of 31
      evaluable patients (23%) had an objective response, 11 (35%) had stable disease
      (six > or = 24 weeks), and the overall clinical benefit rate (objective response
      and/or stable disease > or = 24 weeks) was 42%. CONCLUSIONS: Although the high
      incidence of febrile neutropenia necessitated a multiple scheduling adaptation of
      tipifarnib compared to the original protocol, the apparent lack of mutual
      pharmacokinetic interactions, the ability to coadminister tipifarnib and
      docetaxel near single-agent MTDs, and suggestive evidence of efficacy make this
      drug combination attractive for further examination.

PMID- 17519067
TI  - A 2-night, 3-period, crossover study of ramelteon's efficacy and safety in older
      adults with chronic insomnia.
AB  - OBJECTIVE: To assess the efficacy and safety of ramelteon, a selective melatonin
      MT1/MT2-receptor agonist, for insomnia treatment in older adults. METHODS: In a
      randomized, 9-week, 3-period crossover trial conducted at 17 sleep centers, older
      adults (N = 100) with chronic primary insomnia (37 men, 63 women; mean age
      [range], 70.7 [65-83] years) were administered placebo, ramelteon 4 mg, and
      ramelteon 8 mg in three treatment phases for two consecutive nights. Each phase
      was separated by 5- to 12-day washout periods. Sleep was monitored via
      polysomnography. Subjective sleep parameters, using a Postsleep Questionnaire,
      were recorded, and residual pharmacologic effects were assessed. RESULTS:
      Statistically significant reductions in latency to persistent sleep were observed
      with both ramelteon 4 mg and 8 mg compared to placebo (28.7 min vs. 38.4 min, p <
      0.001; 30.8 min vs. 38.4 min, p = 0.005, respectively). Total sleep time (p =
      0.036 and p = 0.007, respectively) and sleep efficiency (p = 0.037 and p = 0.007,
      respectively) were also significantly improved with ramelteon 4 mg and 8 mg
      compared to placebo. Statistically significant reductions in subjective sleep
      latency on a Postsleep Questionnaire were reported with ramelteon 4 mg versus
      placebo (p = 0.037), but not ramelteon 8 mg (p = 0.120); no significant
      differences on other subjective sleep assessments were reported. A lack of power
      limits interpretation of self-reported sleep parameters. Incidences of adverse
      events considered treatment related were placebo (7%), ramelteon 4 mg (11%), and
      ramelteon 8 mg (5%). No residual pharmacologic effects were observed via Digit
      Symbol Substitution Test, memory recall tests (immediate and delayed), visual
      analog scales (feelings and mood), and Postsleep Questionnaire (level of
      alertness and ability to concentrate). CONCLUSIONS: In older adults with chronic
      primary insomnia, ramelteon produced significant reductions in latency to
      persistent sleep and increases in total sleep time and sleep efficacy, and showed
      no evidence of adverse next-day psychomotor or cognitive effects.

PMID- 17519068
TI  - A comparison of the safety and intraocular pressure lowering of
      bimatoprost/timolol fixed combination versus latanoprost/timolol fixed
      combination in patients with open-angle glaucoma.
AB  - PURPOSE: To compare the efficacy and tolerability of a once daily evening dose of
      the latanoprost/timolol fixed combination (LTFC) with that of a once-daily
      evening dose of the bimatoprost/timolol fixed combination (BTFC) in patients with
      open-angle glaucoma with elevated intraocular pressure (IOP) insufficiently
      responsive to monotherapy with prostaglandin analogues/prostamides. DESIGN:
      Prospective, randomized, evaluator masked, single-center study. PARTICIPANTS: 36
      patients with a diagnosis of open-angle glaucoma, with or without
      pseudoexfoliation, and inadequate control of IOP, insufficiently responsive to
      monotherapy with prostaglandin analogues/prostamides. MAIN OUTCOME MEASURE: The
      primary end-points were the change in IOP at 9:00 am from baseline to week 4, and
      the difference between treatment groups in the mean diurnal IOP reduction from
      baseline to week 4. RESULTS: BTFC provided significantly greater mean diurnal IOP
      reduction [mean (standard deviation)] 2.8 (0.9) mmHg, compared with LTFC 2.1
      (0.6) mmHg, p = 0.0214. Both treatments significantly reduced the IOP from
      baseline at each IOP time-point measured, p < 0.0001, and for the mean diurnal
      IOP; p = 0.0049 for the LTFC, and p < 0.0001 for the BTFC. There were no
      significant differences in average hyperemia scores among groups, 1.25 (0.5) vs.
      1.62 (0.69), p = 0.3835, for the LTFC and the BTFC, respectively. CONCLUSIONS:
      The results of this study showed a significantly higher IOP-lowering effect of a
      once-daily evening dose of the BTFC compared to that of a once-daily evening
      administration of the LTFC.

PMID- 17519069
TI  - Randomized, double-blind, placebo-controlled clinical trial of loperamide plus
      simethicone versus loperamide alone and simethicone alone in the treatment of
      acute diarrhea with gas-related abdominal discomfort.
AB  - OBJECTIVE: To compare efficacy and tolerability of a loperamide/simethicone
      (LOP/SIM) combination product with that of loperamide (LOP) alone, simethicone
      (SIM) alone, and placebo (PBO) for acute nonspecific diarrhea with gas-related
      abdominal discomfort. RESEARCH DESIGN AND METHODS: In this multicenter, double
      blind, 48-h study, patients were randomly assigned to receive two tablets, each
      containing either LOP/SIM 2 mg/125 mg (n = 121), LOP 2 mg (n = 120), SIM 125 mg
      (n = 123), or PBO (n = 121), followed by one tablet after each unformed stool, up
      to four tablets in any 24-h period. The primary outcome measures were time to
      last unformed stool and time to complete relief of gas-related abdominal
      discomfort. For time to last unformed stool, an unformed stool after a 24-h
      period of formed stools or no stools was considered a continuance of the original
      episode (stricter definition) or a new episode (alternate definition). RESULTS: A
      total of 483 patients were included in the intent-to-treat analysis. The median
      time to last unformed stool for LOP/SIM (7.6 h) was significantly shorter than
      that of LOP (11.5 h), SIM (26.0 h), and PBO (29.4 h) (p < or = 0.0232 in
      comparison with survival curves) using the alternate definition; it was
      numerically but not significantly shorter than that of LOP (p = 0.0709) and
      significantly shorter than that of SIM and PBO (p = 0.0001) using the stricter
      definition. LOP/SIM-treated patients had a shorter time to complete relief of gas
      related abdominal discomfort than patients who received either ingredient alone
      or placebo (all p = 0.0001). Few patients reported adverse events in the four
      treatment groups, none of which were serious in nature. Potential study
      limitations include the ability to generalize study results to the population at
      large, variability in total dose consumed, and subjectivity of patient diary
      data. CONCLUSIONS: LOP/SIM was well-tolerated and more efficacious than LOP
      alone, SIM alone, or placebo for acute nonspecific diarrhea and gas-related
      abdominal discomfort.

PMID- 17519070
TI  - Assessing the risk of bone fracture among postmenopausal women who are receiving
      adjuvant hormonal therapy for breast cancer.
AB  - OBJECTIVE: To understand better the true impact of widespread adoption of
      adjuvant aromatase inhibitor (AI) therapy on postmenopausal breast cancer
      patients' risk of bone fracture. METHODS: Data from three different studies were
      used to estimate the relative risk of bone fracture for each of the following
      groups of women (i.e., versus a control group of healthy postmenopausal women):
      (a) healthy postmenopausal women receiving tamoxifen; (b) postmenopausal women
      who had received treatment for early breast cancer; (c) postmenopausal breast
      cancer patients on adjuvant tamoxifen therapy; (d) postmenopausal breast cancer
      patients on adjuvant anastrozole therapy. The results of these analyses were then
      used to estimate the likely incidence of clinical fracture among such populations
      in 'real-life' clinical practice. RESULTS: Breast cancer survivors were
      calculated to be at increased risk of clinical bone fracture (i.e., RR 1.15 vs.
      control group over 5 years). Breast cancer patients initiated on adjuvant
      anastrozole were also calculated to be at increased risk of bone fracture (RR =
      1.36 vs. control group over 5 years), while the calculated risk of fracture among
      tamoxifen-treated breast cancer patients was similar to that observed in the
      control population (RR = 0.91). CONCLUSION: Breast cancer patients are at
      increased risk of clinical bone fracture (compared with the general
      postmenopausal population) and adjuvant anastrozole therapy slightly adds to this
      risk. Importantly, however, the absolute risk of bone fracture appears to remain
      low in each of the evaluated patient populations, suggesting that fear of
      fracture should not prevent the initiation of adjuvant aromatase inhibitor
      therapy.

PMID- 17519071
TI  - Comment and reply on: Randomized trial comparing polymer-coated extended-release
      morphine sulfate to controlled-release oxycodone HCl in moderate to severe
      nonmalignant pain.

PMID- 17519072
TI  - High- versus low-dose fluconazole therapy for empiric treatment of suspected
      invasive candidiasis among high-risk patients in the intensive care unit: a cost
      effectiveness analysis.
AB  - BACKGROUND: High-dose fluconazole is an alternative for patients with candidemia
      caused by Candida glabrata or other Candida species with decreased fluconazole
      susceptibility. However, empiric high-dose fluconazole is not currently
      recommended and may result in higher drug costs and toxicity. OBJECTIVE: To
      determine the cost-effectiveness of using empiric high-dose fluconazole in
      intensive care unit (ICU) with suspected invasive candidiasis. DESIGN: Decision
      analytic model. TARGET POPULATION: ICU patients with suspected invasive
      candidiasis. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Low
      dose fluconazole (loading dose of 800 mg followed by 400 mg daily) vs. high-dose
      fluconazole (loading dose of 1600 mg followed by 800 mg daily). Generic
      fluconazole costs were used for the analysis. OUTCOME MEASURES: Incremental life
      expectancy and incremental cost per discounted life year (DLY) saved. RESULT OF
      BASE-CASE ANALYSIS: Based on current national levels of fluconazole resistance
      and ability to correctly identify patients with candidemia, high-dose fluconazole
      was the more effective but more expensive treatment strategy. Empiric high-dose
      fluconazole therapy decreased the mortality rate by 0.15% compared to low-dose
      strategy with a cost-effectiveness rate of $55,526 per DLY saved. RESULTS OF
      SENSITIVITY ANALYSIS: Empirical high-dose fluconazole was an acceptable treatment
      strategy (using $100,000 per DLY saved as threshold) unless the physical age of
      an ICU survivor was 66 years or older. Empirical high-dose fluconazole was an
      acceptable treatment strategy using $50,000 per DLY saved with minor changes in
      parameters estimates. LIMITATIONS: The estimates of our model may not be
      applicable to all ICU patients. Other hospitals with differences in fluconazole
      resistance, prevalence of invasive candidiasis, or duration of fluconazole
      therapy may produce different results. CONCLUSION: These results suggest that
      empiric high-dose fluconazole therapy should reduce the mortality associated with
      invasive candidiasis at an acceptable cost.

PMID- 17519073
TI  - Bioavailability of triple-bead mixed amphetamine salts compared with a dose
      augmentation strategy of mixed amphetamine salts extended release plus mixed
      amphetamine salts immediate release.
AB  - OBJECTIVE: To compare the single-dose pharmacokinetics of triple-bead mixed
      amphetamine salts (MAS), an oral, once-daily, enhanced extended-release
      amphetamine formulation, with MAS extended release (MAS XR) (Adderall XR) + MAS
      immediate release (MAS IR) administered 8 h later. METHODS: This was a phase I,
      randomized, open-label, single-dose, single-center, two-period, crossover study
      in healthy adult volunteers designed to evaluate the bioavailability of triple
      bead MAS over the course of a full day. Subjects were randomized to triple-bead
      MAS 37.5 mg or MAS XR 25 mg + MAS IR 12.5 mg administered 8 h later (MAS XR + MAS
      IR). The reference treatment was designed to mimic the clinical practice of
      providing extended coverage by supplementing a morning dose of MAS XR with a dose
      of MAS IR 8 h later in order to increase the duration of action. Plasma was
      assayed for d-amphetamine and l-amphetamine. Treatment-emergent adverse events
      (TEAEs), vital signs, electrocardiograms (ECGs), and laboratory data were also
      collected for safety evaluation. RESULTS: Exposure to d- and l-amphetamine was
      equivalent between triple-bead MAS and MAS XR + MAS IR based on maximum plasma
      concentration (Cmax) and area under the plasma concentration-time curve from time
      0 to infinity (AUC(0-infinity)). For Cmax, least-squares mean ratios comparing
      triple-bead MAS with MAS XR + MAS IR were 101.0% and 90.9% for d-amphetamine and
      l-amphetamine, respectively, and for AUC(0-infinity) were 104.4% and 95.3% for d
      amphetamine and l-amphetamine, respectively. Median time to maximum observed
      plasma concentration (Tmax) values for d-amphetamine and l-amphetamine were 8.0 h
      for triple-bead MAS and 10.0 h for MAS XR + MAS IR. There were no clinically
      meaningful differences between the study formulations for TEAEs or laboratory
      values. One subject experienced an ECG abnormality (asymptomatic premature
      ventricular contractions) leading to early termination from the study.
      CONCLUSIONS: In healthy adults, the exposure observed with triple-bead MAS 37.5
      mg was bioequivalent to MAS XR 25 mg supplemented by MAS IR 12.5 mg administered
      8 h later. These data demonstrate that a single morning dose of triple-bead MAS
      provides equivalent plasma concentrations to those observed with a dose
      augmentation strategy of MAS XR in the morning followed by MAS IR in the
      afternoon, while minimizing peak-to-trough fluctuations. Triple-bead MAS was also
      generally well-tolerated in this study.

PMID- 17519074
TI  - LHRH agonists in prostate cancer: frequency of treatment, serum testosterone
      measurement and castrate level: consensus opinion from a roundtable discussion.
AB  - BACKGROUND: Options for lowering testosterone in patients with prostate cancer
      include bilateral orchiectomy, oestrogens and luteinising hormone-releasing
      hormone (LHRH) agonists. LHRH agonists have become widely used in the treatment
      of prostate cancer. ROUNDTABLE ASSEMBLY: In May 2006, a team of experts convened
      a roundtable assembly to discuss key issues associated with the use of LHRH
      agonists in the treatment of prostate cancer. ROUNDTABLE DISCUSSION: The
      discussion centred on the frequency of treatment with LHRH agonists, the role of
      serum testosterone (ST) measurement as part of routine follow-up, and the
      recommended castrate level of ST. Several formulations of LHRH agonists are
      available, including 3-month depots that coincide with visit frequency for
      prostate-specific antigen (PSA) testing. Appropriate monitoring of patients
      receiving LHRH agonists continues to be based on PSA levels. ST determination is
      not recommended as part of routine follow-up, and does not provide additional
      prognostic benefit or improved overall management for the majority of patients.
      However, determination of ST may be useful in selected patients, such as those
      with rising PSA levels or in cases where there is doubt over LHRH agonist
      administration or absorption. Achieving levels of ST similar to those obtained
      after orchiectomy is important for patient outcomes, although there is no
      evidence that a lower ST level (<50 ng/dl) results in additional clinical
      benefits. CONCLUSIONS: LHRH agonists should be considered first-choice
      testosterone-lowering therapy for the treatment of prostate cancer, with the 3
      month depot formulation providing optimal convenience and flexibility. Assessment
      of patients receiving LHRH agonists should be based on PSA levels rather than ST
      levels, although levels of ST similar to those obtained after orchiectomy still
      need to be achieved. Further studies are warranted before the potential
      therapeutic benefit of considerably lowered ST levels can be fully assessed.

PMID- 17519075
TI  - A phase 1, double-blind, placebo-controlled study evaluating single subcutaneous
      administrations of a human interleukin-12/23 monoclonal antibody in subjects with
      plaque psoriasis.
AB  - OBJECTIVE: To evaluate safety, pharmacokinetics, pharmacodynamics, and clinical
      response of single subcutaneous (s.c.) administrations of a human monoclonal
      antibody against the p40 subunit of IL-12/23 (IL-12/23 mAb) in subjects with
      moderate-to-severe psoriasis. METHODS: Twenty-one subjects were enrolled
      sequentially into 4 dose cohorts (0.27, 0.675, 1.35, and 2.7 mg/kg) and
      randomized to IL-12/23 mAb or placebo in a 4:1 ratio. Laboratory/clinical
      parameters and pharmacokinetics were evaluated through Week 24; mRNA cytokine
      expression was measured in psoriatic plaques at Week 1. RESULTS: Mostly mild
      adverse events and no serious adverse events were reported. The pharmacokinetics
      (Cmax and AUC) of IL-12/23 mAb increased in an approximately dose-proportional
      manner. Of the 17 subjects who received IL-12/23 mAb, 13 achieved PASI 75
      (compared with no placebo subjects). mRNA expression of IL-8, IL-18, and IFN
      gamma in psoriatic plaques decreased in subjects with sustained Psoriasis Area
      and Severity Index (PASI) improvement. LIMITATIONS: Interpretation of results is
      limited due to the small sample size in each dose cohort. CONCLUSION: A single
      s.c. administration of IL-12/23 mAb was well tolerated and showed clinical
      response in subjects with moderate-to-severe psoriasis.

PMID- 17519076
TI  - Efficacy and safety of extended-release fluvastatin in Turkish patients with
      hypercholesterolaemia: TULIPS (Turkish Lipid Study).
AB  - OBJECTIVE: The efficacy and safety of extended-release fluvastatin (fluvastatin
      XL), 80 mg once daily, was assessed in Turkish patients with primary
      hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C) 3.37-5.70
      mmol/l and triglyceride (TG) < 4.52 mmol/l). RESEARCH DESIGN: In this open-label,
      prospective, multi-centre study, 154 patients were given fluvastatin XL 80 mg
      once daily and lipid levels were assessed after 2 and 12 weeks. RESULTS:
      Fluvastatin XL 80 mg once daily significantly reduced LDL-C levels by 38.8 and
      38.1% at weeks 2 (n = 140) and 12 (n = 116), respectively (p < 0.001 vs.
      baseline). Treatment with fluvastatin XL for 2 and 12 weeks significantly reduced
      total cholesterol levels by 30.2 and 27.4%, respectively (p < 0.001 vs. baseline)
      and reduced TG levels by 14.9 and 7.5%, respectively (p < 0.001 vs. baseline).
      Following stratification by risk factors for coronary heart disease (CHD)
      according to the National Cholesterol Education Program Adult Treatment Panel III
      guidelines, 87.3% of patients with > or = 2 risk factors, and 67.4% of patients
      with existing CHD or CHD risk equivalents achieved target LDL-C levels (< 3.37
      mmol/l and < 2.59 mmol/l, respectively) with fluvastatin XL. Fluvastatin XL
      reduced high-density lipoprotein cholesterol by 8.9 and 4.7% at weeks 2 and 12
      weeks, respectively. fluvastatin XL 80 mg once daily was generally well
      tolerated. CONCLUSIONS: This open-label study indicates fluvastatin XL 80 mg once
      daily is an effective and well-tolerated lipid-lowering therapy for the reduction
      of CHD risk in Turkish patients.

PMID- 17519077
TI  - The clinical significance of the size of low-density-lipoproteins and the
      modulation of subclasses by fibrates.
AB  - BACKGROUND: Beyond total low-density-lipoproteins (LDL) levels, increasing
      evidence suggests that the 'quality' of LDL exerts a great influence on the
      cardiovascular risk. Several studies have also shown that the therapeutic
      modulation of LDL size is of benefit in reducing the risk of cardiovascular
      events. Hypolipidaemic treatment is able to alter LDL subclass distribution but
      strong variations have been noticed among different agents. Fibrates have a major
      impact on triglyceride metabolism and in modulating LDL size and subclasses, but
      variations exist among the different molecules. METHODOLOGY: A literature search
      (by Medline and Scopus) was performed using the following headings: 'small dense
      LDL', 'LDL size', 'LDL subfractions', 'LDL subclasses', 'LDL distribution' and
      'fenofibrate', 'bezafibrate', 'ciprofibrate' and 'gemfibrozil' up to 20 January
      2007. The authors also manually reviewed the references of selected articles for
      any pertinent material. RESULTS: Analysis of all published studies revealed that
      treatment with fenofibrate, ciprofibrate, bezafibrate and gemfibrozil is usually
      beneficial, and fenofibrate may be more efficacious than the other molecules.
      This is supported by using all the available techniques in subjects with a very
      wide range of lipid alterations. CONCLUSION: Among the different agents,
      fenofibrate has been found to be particularly effective in modulating LDL size
      and subclasses in patients at higher cardiovascular risk, such as those with type
      2 diabetes or the metabolic syndrome.

PMID- 17519078
TI  - A cost-effectiveness analysis of immunotherapy with SQ allergen extract for
      patients with seasonal allergic rhinoconjunctivitis in selected European
      countries.
AB  - BACKGROUND: Seasonal allergic rhinoconjunctivitis can, for some people, reduce
      quality of life and the ability to cope with everyday tasks. SCOPE: In this paper
      we investigate the cost-effectiveness of immunization therapy with Alutard SQ
      (ASQ) and compare the cost-effectiveness in countries where the therapy has been
      in use in order to assess the impact of national therapeutic practices on the
      results of health economic assessments. Data are obtained from a clinical trial
      carried out in 2001-2002. To evaluate the cost-effectiveness of immunization we
      have added data on resource use in Austria, Denmark, Finland, Germany, The
      Netherlands, and Sweden. FINDINGS: The computations result in cost-effectiveness
      ratios for allergen immunization between 10,000 euros and 20,000 euros per QALY
      even without provision for indirect costs, and achieving dominance in most
      countries where indirect costs have also been taken into account. The country
      comparisons show that the direct cost of administrating the up-dosing and
      maintenance differs considerably between countries, and that the cost of medical
      staff is substantial, constituting in most cases more than half of the direct
      costs of the immunization therapy. CONCLUSION: The study shows that immunotherapy
      with SQ allergen extract is cost-effective in a wide range of national
      environments, and that cost-effectiveness differences by country are largely a
      result of different practices in the up-dosing phase.

PMID- 17519079
TI  - Comparative effectiveness of rosuvastatin versus other statin therapies in
      patients at increased risk of failure to achieve low-density lipoprotein goals.
AB  - OBJECTIVES: Statins are increasingly used in the treatment of
      hypercholesterolemia. Research has shown difficulty in attaining LDL-C goals in
      routine clinical practice, especially in patients at high risk for coronary
      events. This study identified risk factors associated with failure to attain LDL
      C goals in routine clinical practice and examined the effectiveness of
      rosuvastatin compared to other statins in patients presenting with these risk
      factors. METHODS: This retrospective observational study used administrative
      claims data on patients receiving statins. After stratifying patients into
      baseline National Cholesterol Education Program Adult Treatment Panel III (NCEP
      ATP III) risk categories, logistic regression allowed identification of factors
      predicting failure to attain LDL-C goal. Separate analyses compared failure rates
      between rosuvastatin and other statins in patients at an increased risk of goal
      attainment failure. RESULTS: Of the 4661 patients identified, 50% and 14% had
      baseline NCEP ATP III high and moderate risk status, respectively. Risk factors
      associated with goal attainment failure were percentage change required to
      achieve goal > or = 30%, NCEP high risk status, percentage change required 15
      29%, and NCEP moderate risk status. Patients at an increased risk of failure
      exhibited significantly higher failure rates in all other statin groups compared
      to rosuvastatin. CONCLUSIONS: This study demonstrates that patients requiring >
      or = 15% change in LDL-C or NCEP high or moderate risk patients are at a higher
      risk of goal attainment failure. Rosuvastatin is more effective compared to other
      statins in patients with these risk factors and given variations in clinical
      profiles of branded and generic statins, these results may aid in identifying
      patients most likely to benefit from rosuvastatin compared to other statin
      therapies. Validating the results of this study in other patient populations
      would help increase the generalizability of study findings.

PMID- 17519080
TI  - Effect of the novel oral dipeptidyl peptidase IV inhibitor vildagliptin on the
      pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.
AB  - OBJECTIVE: Vildagliptin is a potent and selective dipeptidyl peptidase-IV (DPP-4)
      inhibitor that improves glycemic control in patients with type 2 diabetes by
      increasing alpha and beta-cell responsiveness to glucose. This study assessed the
      effect of multiple doses of vildagliptin 100 mg once daily on warfarin
      pharmacokinetics and pharmacodynamics following a single 25 mg oral dose of
      warfarin sodium. RESEARCH DESIGN AND METHODS: Open-label, randomized, two-period,
      two-treatment crossover study in 16 healthy subjects. RESULTS: The geometric mean
      ratios (co-administration vs. administration alone) and 90% confidence intervals
      (CIs) for the area under the plasma concentration-time curve (AUC) of
      vildagliptin, R- and S-warfarin were 1.04 (0.98, 1.11), 1.00 (0.95, 1.04) and
      0.97 (0.93, 1.01), respectively. The 90% CI of the ratios for vildagliptin, R-
      and S-warfarin maximum plasma concentration (Cmax) were also within the
      equivalence range 0.80-1.25. Geometric mean ratios (co-administration vs.
      warfarin alone) of the maximum value and AUC for prothrombin time (PT(max), 1.00
      [90% CI 0.97, 1.04]; AUC(PT), 0.99 [0.97, 1.01]) and international normalized
      ratios (INRmax, 1.01 [0.98, 1.05]; AUC(INR), 0.99 [0.97, 1.01]) were near unity
      with the 90% CI within the range 0.80-1.25. Vildagliptin was well tolerated alone
      or co-administered with warfarin; only one adverse event (upper respiratory tract
      infection in a subject receiving warfarin alone) was reported, which was judged
      not to be related to study medication. CONCLUSIONS: Co-administration of warfarin
      with vildagliptin did not alter the pharmacokinetics and pharmacodynamics of R-
      or S-warfarin. The pharmacokinetics of vildagliptin were not affected by
      warfarin. No dosage adjustment of either warfarin or vildagliptin is necessary
      when these drugs are co-medicated.

PMID- 17519081
TI  - Differentiating prescription omega-3-acid ethyl esters (P-OM3) from dietary
      supplement omega-3 fatty acids.
AB  - BACKGROUND: A reliable means of treating hyper-triglyceridemia is the use of
      large doses of the omega-3 fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA). Modest levels of EPA and DHA may be obtained from
      food, particularly fatty fish. OBJECTIVES: This article is intended to review
      clinically relevant differences between dietary-supplement omega-3 fatty acids
      and prescription omega-3-acid ethyl esters (P-OM3). METHODS: PubMed and the Food
      and Drug Administration (FDA) Website were searched for articles published
      between 1995 and 2007 that contained the terms fish oil, fatty acids, n-3 fatty
      acids, omega fatty acids, docosahexaenoic acid, or eicosapentaenoic acid.
      Articles discussing sources, recommended intake, and differences among various
      formulations of omega-3 fatty acids were selected for review. A limitation to
      this review is the lack of head-to-head clinical trials using P-OM3 and dietary
      supplement omega-3 fatty acids. RESULTS: Many types of nonprescription dietary
      supplements of omega-3 fatty acids are available; however, the efficacy, quality,
      and safety of these products are open to question because they are not regulated
      by the same standards as pharmaceutical agents. P-OM3 is the only omega-3 fatty
      acid product (Omacor capsules) approved by the US FDA available in the United
      States as an adjunct to diet to reduce very high (> or = 500 mg/dL) triglyceride
      levels in adult patients. CONCLUSIONS: P-OM3 can be used with confidence by
      practitioners who want to provide therapeutic doses of omega-3 fatty acids in a
      preparation that has been documented to be both safe and effective.

PMID- 17519082
TI  - Cost-effectiveness of salmeterol xinafoate/fluticasone propionate combination
      inhaler in chronic asthma.
AB  - OBJECTIVE: To determine where in the treatment steps recommended by the British
      Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN)
      Asthma Guideline it is cost-effective to use salmeterol xinafoate/fluticasone
      propionate combination inhaler (SFC) (Seretide) compared with other inhaled
      corticosteroid (ICS) containing regimens (with and without a long acting beta-2
      agonist (LABA)) for chronic asthma in adults and children. RESEARCH DESIGN AND
      METHODS: Meta-analyses of percentage symptom-free days (%SFD) were used within a
      cost-effectiveness model. Time spent in two asthma control health states,
      'symptom-free' and 'with-symptoms' was used as the measure of differential
      treatment effectiveness. SFC was compared with varying doses of fluticasone
      propionate (FP) and beclometasone dipropionate (BDP) with or without a separate
      salmeterol inhaler, and with the budesonide/formoterol combination inhaler
      (BUD/FORM) (Symbicort). Drug costs, non-drug costs and quality adjusted life
      years (QALY) were incorporated into the analyses. Results are presented as cost
      per QALY ratios and uncertainty explored using probabilistic sensitivity
      analysis. RESULTS: Compared with an increased dose of FP in adults, SFC either
      'dominates' (i.e. cheaper and more effective) FP or the cost per QALY is 6852
      pounds sterling. The cost per QALYs estimated in sensitivity analyses using BDP
      costs range from 5679 pounds sterling to 15,997 pounds sterling. For children the
      cost per QALY for SFC 50 Evohaler compared with an increased dose of FP is pound
      15,739 pounds sterling. SFC is similarly clinically effective in improving %SFDs
      compared with FP plus salmeterol delivered in separate inhalers (mean differences
      for each dose comparison of -3.9 (low) (with a 95% confidence interval (CI): 
      12.96; 5.16); 4.10 (medium) (95% CI: -3.01; 11.21); -0.4 (high) (95% CI: -8.88;
      8.08)) and BUD/FORM (mean difference of 0.40 (95% CI -3.69; 4.49)) in adults, and
      a cheaper SFC option is available at all doses (annual cost savings range from 18
      pounds sterling-427 pounds sterling per patient). SFC was similarly effective
      compared with FP plus salmeterol in separate inhalers in children under 12 and
      also resulted in annual cost savings of between 47 pounds sterling and 77 pounds
      sterling. A number of other comparisons were also made and the results are
      available as electronic supplementary data. CONCLUSIONS: This is the first
      analysis to estimate the cost-effectiveness of SFC in chronic asthma compared
      with multiple comparators and based on a systematic identification of relevant
      trials and data on %SFDs. The findings suggest that for adults and children
      uncontrolled on BDP 400 microg/day or equivalent it is a cost-effective option to
      switch to SFC (at an equivalent ICS dose) compared with increasing the dose of
      ICS. For adults and children aged 12 years and over who have passed this point
      and are uncontrolled on BDP 800 microg/day or equivalent, switching to SFC
      remains a cost-effective approach. Where an adult or child requires an ICS and a
      LABA to be co-prescribed, SFC is a cost-effective option compared with FP or BDP
      plus salmeterol delivered in separate inhalers. In adults who require combination
      therapy, SFC is a cost-effective option compared with BUD/FORM.

PMID- 17519083
TI  - Phase I study to determine the MTD of paclitaxel given three times per week
      during concurrent radiation therapy for stage III non-small cell lung cancer.
AB  - OBJECTIVE: To evaluate the toxicity and the maximum tolerated dose (MTD) of
      paclitaxel concurrently with three-dimensional (3D) conformal radiotherapy for
      patients with locally advanced non-small cell lung cancer (LANSCLC) after 2-3
      cycles of induction chemotherapy. RESEARCH DESIGN AND METHODS: Patients with
      histologically proven stage III non-small cell lung cancer (NSCLC) were eligible.
      Induction chemotherapy regimen included cisplatin (40 mg/m2) on days 1 and 2, and
      vinorelbine (25 mg/m2) on days 1 and 8 every 3 weeks for 2 or 3 cycles, followed
      a month later by continual three-dimensional (3D) conformal radiotherapy (60 Gy
      in 30 fractions for 6 weeks) delivered concurrently with paclitaxel dose
      escalating from the lowest level, 15 mg/m2, twice weekly, 6 weeks in all, to the
      highest level, 15 mg/m2, three times a week, 6 weeks in all. MAIN OUTCOME
      MEASURES: The MTD was defined as the highest safely tolerated dose at which no
      more than one patient out of six experiences dose-limiting toxicity, with the
      next higher dose having at least two out of six patients experience dose-limiting
      toxicity (DLT). RESULTS: Twenty-three patients were enrolled in this study. The
      maximum tolerated dose of paclitaxel during 3D-conformal radiotherapy was not
      reached at 15 mg/m2, three times a week, 6 weeks in all, a level which has been
      recommended for Caucasian patients with LANSCLC without induction chemotherapy.
      The overall response rate of induction chemotherapy alone was 47.8% (0% complete
      remission, 47.8% partial remission, 39.1% stable disease, 13% progressive
      disease) and that of induction chemotherapy plus concurrent treatment was 78.3%
      (18/23), including 8.7% (2/23) complete remissions. None of the patients died as
      a result of toxicity. The median survival time was 23.0 months. CONCLUSIONS: 15
      mg/m2 of paclitaxel, three times a week, concurrently with 3D-conformal
      radiotherapy for patients with locally advanced NSCLC after 2 or 3 cycles of
      induction chemotherapy is a safe and effective dose, according to our preliminary
      study.

PMID- 17519084
TI  - Effect of ezetimibe monotherapy on the concentration of lipoprotein subfractions
      in patients with primary dyslipidaemia.
AB  - BACKGROUND: Recent studies suggest that the distribution of lipoprotein
      subfractions is an independent predictor of vascular events. Therefore, we
      evaluated the effect of ezetimibe (a selective cholesterol transport inhibitor)
      on the concentrations of lipoprotein subfractions in patients with primary
      dyslipidaemia. MATERIALS AND METHODS: Patients (n = 50) with primary
      dyslipidaemias were recruited. The concentrations of the individual lipoprotein
      subfractions were measured using the Lipoprint system at baseline and after 16
      weeks of treatment. RESULTS: Ezetimibe reduced total, low-density lipoprotein
      cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) values
      as well as apolipoprotein B concentrations. Subfractionation of apolipoprotein B
      containing lipoproteins showed that the reduction in LDL-C values was due to a
      fall in the concentrations of all LDL subfractions. However, a more pronounced
      trend towards a decrease in the concentrations of dense LDL subfractions was
      observed. Patients with triglyceride values >1.7 mmol/L had significantly greater
      reductions in the concentrations of small, dense LDL particles compared with
      those with normal triglyceride levels (49 vs. 19%, respectively; p < 0.05).
      Ezetimibe decreased the concentrations of HDL-C mainly due to a fall in the
      concentration of dense HDL subfractions. CONCLUSION: Ezetimibe can favourably
      affect the distribution of LDL subfractions, especially in patients with elevated
      triglyceride values. Further studies are needed to clarify the significance of
      the ezetimibe-induced reduction in the concentrations of dense HDL particles.

PMID- 17519085
TI  - The relationship between statin use and atrial fibrillation.
AB  - OBJECTIVE: To investigate the relationship between statin therapy and the
      development of new-onset, recurrent, and postoperative atrial fibrillation (AF).
      RESEARCH DESIGN AND METHODS: A systematic literature search was conducted through
      September 2006. Included studies were either randomized, controlled trials or
      observational studies with adjusted analyses using multivariate regression or
      covariate matching, compared patients receiving or not receiving a statin, and
      reported data on the incidence of AF. Weighted averages were reported as odds
      ratios with 95% confidence intervals (CIs) using a random-effects model. MAIN
      OUTCOME MEASURES: The primary outcome measured was a combined endpoint of any AF
      type. Secondary outcomes included new-onset, recurrent, and postoperative AF.
      RESULTS: Fourteen trials reporting the results of 15 unique analyses (n = 7402)
      were included. There was a 20% incidence rate for any AF with varying rates
      depending on AF type (new-onset [11%], recurrent [56%], recurrent after
      cardioversion [54%], postoperative [22%]). The use of a statin reduced the odds
      of developing any AF by 45% (odds ratio [OR] 0.55; 95% CI 0.43-0.70); Q statistic
      p = 0.001). Statins reduced the odds of developing new-onset AF by 32% (OR 0.68;
      95% CI 0.51-0.90), recurrent AF by 57% (OR 0.43; 95% CI 0.24-0.79), recurrent AF
      after cardioversion by 42% (OR 0.58; 95% CI 0.32-1.05) and postoperative AF by
      58% (OR 0.42; 95% CI 0.27-0.65). LIMITATIONS: We considered studies that were
      observational in nature or only available in abstract form. Publication bias
      could not be ruled out. CONCLUSIONS: Statin therapy was associated with a reduced
      odds of developing AF, thus providing evidence of the benefit of statins beyond
      the lipid-lowering activity.

PMID- 17519086
TI  - Cost-effectiveness of memantine in moderate-to-severe Alzheimer's disease
      patients receiving donepezil.
AB  - OBJECTIVE: The efficacy and safety of memantine in patients with moderate-to
      severe Alzheimer's disease (AD) receiving stable doses of donepezil were recently
      demonstrated in a phase III trial. The cost-effectiveness of such therapy is
      unknown. RESEARCH DESIGN AND METHODS: A microsimulation model was developed to
      depict AD progression over time and associated clinical and economic outcomes. AD
      progression was measured in terms of decline in cognitive function, as assessed
      by the Severe Impairment Battery (SIB). At model entry, patients were assumed to
      have moderate-to-severe AD, to be on stable doses of donepezil, and to begin
      combination therapy with memantine, or continue to receive donepezil alone;
      duration of therapy was assumed to be 1 year. Drug efficacy was based on data
      from a phase III trial. Key assumptions of the model included: (1) efficacy of
      study drugs would extend to 1 year; (2) measures of cognitive function could be
      mapped to one another, as well as to global measures of disease severity; and (3)
      following therapy discontinuation, cognitive function would revert immediately to
      natural history levels. Cost-effectiveness was assessed in terms of cost (2005
      US$) per quality-adjusted life-year (QALY) gained over a lifetime (3% discount
      rate). RESULTS: SIB scores were estimated to improve by 3.3 over 1 year from
      therapy with memantine plus donepezil (vs. donepezil alone). While
      pharmacotherapy costs were estimated to increase by $1250 during the year of
      memantine treatment, costs of formal and informal services were estimated to
      decrease by $1240 over this period and by $1493 (discounted present value) over a
      lifetime. Findings were sensitive to the assumed SIB score at therapy initiation;
      cost-effectiveness was better for patients with higher initial SIB scores (i.e.,
      less severe disease). CONCLUSION: In patients with moderate-to-severe AD already
      receiving donepezil, treatment with memantine results in improved clinical
      outcomes and reduced total costs of care.

PMID- 17519087
TI  - Ethics reflection in development cooperation: a critical role for The Union.

PMID- 17519088
TI  - Learning about tuberculosis in medical schools.

PMID- 17519089
TI  - Risk of tuberculosis infection and disease associated with work in health care
      settings.
AB  - BACKGROUND: Tuberculosis (TB) in health care workers (HCWs) was not considered a
      serious problem following the advent of effective antibiotic therapy. Interest
      was re-stimulated by the occurrence of several major nosocomial outbreaks.
      METHODS: We have reviewed the available published literature regarding prevalence
      and incidence of TB infection and disease among HCWs in countries categorised by
      mean income. We included studies published in English since 1960 from low- and
      middle-income countries (LMICs) and since 1990 from high-income countries (HICs).
      We excluded outbreak reports and studies based only on questionnaires. RESULTS:
      The median prevalence of latent TB infection (LTBI) in HCWs was 63% (range 33
      79%) in LMICs and 24% in HICs (4-46%). Among HCWs from LMICs, LTBI was
      consistently associated with markers of occupational exposure, but in HICs it was
      more often associated with non-occupational factors. The median annual incidence
      of TB infection attributable to health care work was 5.8% (range 0-11%) in LMICs
      and 1.1% (0.2-12%) in HICs. Rates of active TB in HCWs were consistently higher
      than in the general population in all countries, although findings were variable
      in HICs. Administrative infection control measures had a modest impact in LMICs,
      yet seemed the most effective in HICs. CONCLUSIONS: TB remains a very important
      occupational risk for HCWs in LMICs and for workers in some institutions in HICs.
      Risk appears particularly high when there is increased exposure combined with
      inadequate infection control measures.

PMID- 17519090
TI  - Linezolid for the treatment of patients with [corrected] mycobacterial infections
      [corrected] a systematic review.
AB  - We searched PubMed and Cochrane databases to review the available evidence
      regarding the use of linezolid in combination with other drugs for the treatment
      of patients with mycobacterial infection. Case reports, case series, prospective
      and retrospective studies, and randomized controlled trials were eligible for
      inclusion in our systematic review if they evaluated the effectiveness and safety
      of linezolid for the treatment of patients with mycobacterial infection. Four
      studies were available, including 24 cases of patients with [corrected]
      mycobacterial infection. Cure of the infection, defined as sterilization of
      mycobacterial cultures or resolution of symptoms, was achieved in 15 of the 24
      cases (62.5%) with mycobacterial infection (mainly tuberculosis). Sterile
      cultures were also achieved in three other cases, although the patients had
      stopped linezolid (two because of optic neuropathy and one due to economic
      reasons; all three continued on second-line therapy). On the other hand, serious
      adverse events were observed in the majority of patients with mycobacterial
      infection treated with combinations that included linezolid (18/24, 75%).
      Neuropathy (peripheral and/or optic) and anemia were reported in 11/24 (45.8%)
      and 10/24 (41.7%) cases, respectively. Although the limited evidence suggests
      that linezolid may be considered as a second-line agent for mycobacterial
      infections, any treatment with linezolid should be weighed against the risks
      associated with its long-term use.

PMID- 17519091
TI  - Tobacco cessation and brief advice.
AB  - Patients who are enrolled on tuberculosis (TB) treatment are often ill and are
      seeking ways to get better. They are more likely at that time to adopt risk
      reducing health behaviours. Interventions that are neither complicated nor time
      consuming are available to health service personnel to help patients undertake
      smoking cessation. Brief advice to patients repeated at various times throughout
      their TB care can increase cessation rates. All tobacco use needs to be
      identified and reasons for quitting enunciated. Patients are thus given a
      framework for considering smoking cessation. If patients then choose not to stop
      currently, they can be asked to reconsider at a later visit, and also be
      cautioned to avoid smoking in the presence of others. Smokers who want to stop
      can discuss strategies for avoiding craving and withdrawal, and pharmacological
      agents can be recommended if they are available. Because the brief advice is
      repeated, patients are reinforced either for having stopped or for their progress
      towards stopping.

PMID- 17519092
TI  - Ethical issues in research in low-income countries.
AB  - During the twentieth century, spectacular developments in science, technology and
      medical practice coupled with economic growth have transformed health care and
      improved the lives of many people. Despite such progress, the world today is more
      inequitable than it was 50 years ago: disparities in wealth and health are
      widening inexorably, and infectious diseases are again becoming a major scourge
      and pose a threat to the lives of all. Hundreds of millions of people live in
      degrading poverty, with little, if any, access to health care. Recognition of
      this context in which much research takes place should sharpen our focus on the
      ethical requirements for research that could improve the health of a greater
      proportion of the world's population--one of the most pressing moral problems of
      our time. The intense debate on ethical dilemmas associated with an expanding
      programme of clinical research in developing countries has revealed much common
      ground, but has also left a residuum of controversy. We suggest that contested
      issues could be resolved by paying greater attention to different world views on
      the relationship between research and clinical care and by defining policies that
      both progressively improve the standard of care in research and link research to
      improved delivery of health care in developing countries.

PMID- 17519093
TI  - Antibody markers of incident tuberculosis among HIV-infected adults in the USA: a
      historical prospective study.
AB  - OBJECTIVE: To assess whether serum levels of antibodies against Mycobacterium
      tuberculosis antigens increase before diagnosis of active tuberculosis (TB).
      DESIGN: Serial serum samples were obtained from 30 human immunodeficiency virus
      (HIV) co-infected individuals who developed active TB during a multicenter
      prospective study on pulmonary complications of HIV/AIDS conducted among >1300
      subjects in the USA in the 1980s. Multiple serum samples from 47 matched control
      individuals who did not develop TB in the same study were also tested.
      Immunoglobulin G (IgG) antibodies to 10 M. tuberculosis proteins were detected by
      enzyme-linked immunosorbent assay (ELISA), and data were analyzed by descriptive
      and inferential statistical techniques to assess patterns, trends and differences
      in antibody levels relative to time from TB diagnosis. RESULTS: Antibodies to
      five antigens (ESAT-6, 38 kDa Ag, 16 kDa Ag, malate synthase and MTSA-10/CFP-10),
      but not to five other antigens (Rv2626c, ferredoxin A, glutamine synthetase,
      alanine dehydrogenase and Ag85) increased before diagnosis of TB relative to
      control levels. The earliest increase in the TB group was detected for MTSA
      10/CFP-10 (24-30 months pre-diagnosis). CONCLUSIONS: Levels of serum antibodies
      to particular proteins of M. tuberculosis increase before microbiological and
      clinical symptoms of active TB. The use of antibody biomarkers for prognostic
      purposes should therefore be feasible.

PMID- 17519094
TI  - Use of geographic and genotyping tools to characterise tuberculosis transmission
      in Montreal.
AB  - SETTING: In Canada, tuberculosis (TB) is increasingly an urban health problem.
      Montreal is Canada's second-largest city and the second most frequent destination
      for new immigrants and refugees. OBJECTIVES: To detect spatial aggregation of
      cases, areas of excess incidence and local 'hot spots' of transmission in
      Montreal. DESIGN: We used residential addresses to geocode active TB cases
      reported on the Island of Montreal in 1996-2000. After a hot spot analysis
      suggested two areas of overconcentration, we conducted a spatial scan, with
      census tracts (population 2500-8000) as the primary unit of analysis and
      stratification by birthplace. We linked these analyses with genotyping of all
      available Mycobacterium tuberculosis isolates, using IS6110-RFLP and
      spoligotyping. RESULTS: We identified four areas of excess incidence among the
      foreign-born (incidence rate ratios 1.3-4.1, relative to the entire Island) and
      one such area among the Canadian-born (incidence rate ratio 2.3). There was
      partial overlap with the two hot spots. Genotyping indicated ongoing transmission
      among the foreign-born within the largest high-incidence zone. While this zone
      overlapped the area of high incidence among Canadian-born, genotyping largely
      excluded transmission between the two groups. CONCLUSIONS: In a city with low
      overall incidence, spatial and molecular analyses highlighted ongoing local
      transmission.

PMID- 17519095
TI  - Variables associated with diagnostic delay in immigrant groups with tuberculosis
      in Madrid.
AB  - OBJECTIVE: To identify variables associated with total diagnostic delay (TDD),
      patient delay (PD) and health service delay (HSD), among the tuberculous
      immigrant population in the Autonomous Community of Madrid (ACT). METHODOLOGY:
      Tuberculosis cases diagnosed in 15 hospitals in the ACT in 2003 were interviewed
      face-to-face and medical records were reviewed. A descriptive study was
      conducted, followed by univariate and multivariate analysis using non-conditional
      logistic regressions. 50th (p50) and 75th (p75) percentiles of the different
      diagnostic delay components were analysed as dependent variables. RESULTS: For
      the 296 cases included, the mean TDD was 40.5 days (IQR 16.0-90.0), the PD was 15
      days (IQR 6.5-30.0), and the HSD was 5 days (IQR 0.0-30.0). TDD-p75 is associated
      with seeking primary health care (OR 2.87, 95%CI 1.47-5.58). PD-p75 is associated
      with identification of fever (OR 0.49, 95%CI 0.25-0.92) and non-identification of
      cough (OR 1.87, 95%CI 1.05-3.36) as symptoms resulting in health care being
      sought. The HSD-p75 is associated with primary health care being sought (OR 3.81,
      95%CI 1.87-7.78), health cover (OR 15.07, 95%CI 1.96-115.68) and negative smear
      results at the time of diagnosis (OR 1.98, 95%CI 1.01-3.91). CONCLUSIONS: The HSD
      needs to be reduced, mainly when health care is sought through the primary care
      services and among patients with negative smear results.

PMID- 17519096
TI  - Clinical and epidemiological evaluation of tuberculosis in Serbia, 1990-2004.
AB  - SETTING: Republic of Serbia, excluding Kosovo. OBJECTIVE: To estimate the
      clinical and epidemiological pattern of tuberculosis (TB) in Serbia during the
      period 1990-2004. DESIGN: A retrospective analysis of clinical and
      epidemiological data on TB patients registered in annual TB reports. RESULTS:
      During the 15-year period, TB incidence levelled off in Serbia. The slightly
      decreasing trend occurred in both total pulmonary TB (PTB) and laboratory
      confirmed PTB (PTB+) incidence (P > 0.05), while the trend of extra-pulmonary TB
      (EPTB) incidence increased slightly (P > 0.05). During the same period, TB
      mortality showed a significantly decreasing trend (P < 0.05). The mean annual
      proportion of PTB+ cases among newly reported PTB cases was 62.7%. The mean
      proportion of EPTB cases among total TB cases was 6.1%. The mean percentage of
      cases with resistance to at least one anti-tuberculosis drug was 4.8%.
      CONCLUSION: Thanks to the good organisation and efficient work of anti
      tuberculosis dispensaries in Serbia, as well as to the low incidence of AIDS and
      low frequency of Mycobacterium tuberculosis resistant strains, TB incidence did
      not increase during the period observed and TB mortality significantly decreased,
      despite markedly deteriorated socio-economic conditions during the 1990s.

PMID- 17519097
TI  - Mycobacterium caprae in cattle and humans in Croatia.
AB  - SETTING: This paper describes an outbreak of human and related bovine
      tuberculosis (TB) caused by Mycobacterium caprae in Croatia. A 13-year-old boy
      clinically presented enlargement of cervical lymph node with consecutive
      isolation of M. caprae. His 7-year-old sister, who had no clinical signs of
      disease, hyper-reacted to the purified protein derivative (PPD) test (>25 mm) and
      peribronchial infiltration was found by radiology. The children came from a
      family that ran a small-sized cattle dairy farm. DESIGN: All cattle on the farm
      were subjected to cutaneous TB testing: six of the 14 reacted positive, while
      three were suspicious. The entire herd was slaughtered, their carcasses examined
      and collected material subjected to pertinent diagnostic procedures. RESULTS:
      Gross examination findings consistent with TB were observed in the PPD-positive
      cows. Mycobacteria isolated from the boy and cattle were identified by classical
      and molecular methods, confirming M. caprae as the causative agent. CONCLUSION:
      Although not bacteriologically proven, consumption of raw milk or non-pasteurised
      milk products from infected dairy cattle was suspected as the source of infection
      in humans. Our findings confirm the domination of M. caprae among cattle in
      Croatia and represent the first evidence of M. caprae infection in humans in
      Croatia.

PMID- 17519098
TI  - Efficiency of a third serial sputum smear examination in the diagnosis of
      tuberculosis in Moldova and Uganda.
AB  - SETTING: Twenty-four and 30 tuberculosis (TB) microscopy laboratories in Moldova
      and Uganda, respectively. OBJECTIVE: To estimate the workload required to
      identify one additional case of TB with a third serial sputum smear examination.
      METHODS: Retrospective laboratory register study to determine the prevalence and
      the incremental yield of TB cases from a third serial sputum smear examination
      among suspects in Moldova and Uganda, with the reciprocal of the product of these
      two fractions providing the number of examinations required to identify one
      additional TB case. RESULTS: In Moldova, 9% (1141/12525) and in Uganda 20%
      (7280/36054) of suspects met the TB case definition with at least one positive
      sputum smear. The incremental yield from the third examination was 4% in Moldova
      and 3% in Uganda. To detect one additional TB case on a third smear, 273
      examinations (95%CI 200-389) in Moldova and 175 (95%CI 153-222) in Uganda were
      thus required. This corresponded to an average of 11 days (8-16) and 7 days (6
      9), respectively, to diagnose one additional case of TB. CONCLUSION: In both
      countries, the third serial sputum smear examination was inefficient in
      diagnosing sputum smear-positive TB.

PMID- 17519099
TI  - Improving sputum microscopy services for the diagnosis of tuberculosis in Peru
      and Bolivia.
AB  - SETTING: Sixteen primary care health centres in Peru and Bolivia. OBJECTIVES: To
      assess the utilisation of microscopy services in Peru and Bolivia and determine
      if clinical audit, a quality improvement tool, improves the utilisation of these
      services. DESIGN: We estimated the percentage of patients with suspected
      tuberculosis (TB) in whom sputum microscopy was effectively utilised in Peru and
      Bolivia over two 6-month periods before and after a clinical audit intervention
      that included standards setting, measuring clinical performance and feedback.
      RESULTS: Before the intervention, only 31% (95%CI 27-35) of TB suspects were
      assessed with sputum microscopy in Peru. In Bolivia, 30% (95%CI 25-35) underwent
      at least two sputum microscopy examinations. After clinical audit, the
      availability of sputum microscopy results improved by respectively 7% (95%CI 1
      12, P < 0.05) and 23% (95%CI 15-30, P < 0.05) over 2 years in Peru and Bolivia.
      CONCLUSIONS: Despite World Health Organization recommendations that all TB
      suspects should undergo sputum microscopy before treatment, results are available
      for further assessment for only one third. This is a potentially serious obstacle
      to TB case detection. Clinical audit can bring some improvement. We recommend
      regular monitoring of effective utilisation of microscopy services and
      investigations to ascertain organisational and structural issues in their uptake
      and use.

PMID- 17519100
TI  - Comparative assays of the rpoB gene for identification of Mycobacterium
      tuberculosis isolated from patients in Sudan.
AB  - OBJECTIVES: To characterise mycobacterial clinical isolates based on
      amplification of the rpoB gene. SETTING: One hundred and thirty-five
      mycobacterial isolates cultured from suspected pulmonary tuberculosis (TB)
      patients were identified phenotypically. Molecular characterisation of the
      isolates was performed based on amplification of the rpoB gene, using duplex
      polymerase chain reaction (DPCR), PCR-restriction fragment length polymorphism
      (RFLP) and nested PCR-based sequence analysis techniques. RESULTS: The DPCR assay
      identified 129 of 135 (95.5%) clinical isolates as Mycobacterium tuberculosis
      complex species. Restriction enzyme analysis of the rpoB PCR product using Hind
      II identified 134 of the 135 (99.3%) isolates as M. tuberculosis complex, while
      nested PCR sequence analysis of the rpoB gene identified 133/133 examined
      isolates (100%) as M. tuberculosis species. No mycobacteria other than M.
      tuberculosis (MOTT) were detected among the studied isolates. CONCLUSION: DPCR,
      PCR/RFLP Hind II and nested PCR sequence analysis of the rpoB gene techniques
      showed comparable efficiency in the characterisation of Mycobacterium isolates.
      Nested PCR sequence analysis of the rpoB gene was superior to PCR/RFLP for
      characterisation of suspected M. tuberculosis isolates, while the DPCR technique
      showed less sensitivity. As PCR-RFLP requires less sophisticated laboratory
      facilities than nested PCR sequence analysis, it would be more appropriate to be
      adopted for accurate characterisation of mycobacteria in countries with a weak
      infrastructure.

PMID- 17519101
TI  - Utility of three mammalian cell entry proteins of Mycobacterium tuberculosis in
      the serodiagnosis of tuberculosis.
AB  - SETTING: The mammalian cell entry (mce) proteins Mce3A, Mce3D and Mce3E, encoded
      by the mce3 operon of Mycobacterium tuberculosis, have recently been shown to be
      expressed during natural infection in humans. OBJECTIVE: To determine the
      potential of Mce3A, Mce3D and Mce3E proteins in the serodiagnosis of tuberculosis
      (TB). DESIGN: The quantitative detection of anti-Mce3A, -Mce3D and -Mce3E
      antibodies in serum samples from active TB patients (n = 58), healthy contacts of
      TB patients (n = 24) and bacilli Calmette-Guerin (BCG) vaccinated healthy
      subjects (n = 24) was performed using enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Antibodies in serum from 98%, 86% and 90% of active TB patients and from
      92%, 75% and 96% of healthy contacts of TB patients reacted with Mce3A, Mce3D and
      Mce3E proteins, respectively. However, none of the serum from BCG-vaccinated
      healthy subjects reacted with Mce3A and Mce3E proteins, and only 8% of serum
      samples reacted with Mce3D protein. Overall, serum from 98% active TB patients,
      96% healthy contacts and 0% BCG-vaccinated healthy subjects were positive for
      anti-Mce3A and/or -Mce3E antibodies. CONCLUSIONS: Our results suggest that Mce3A
      and Mce3E proteins may be useful for the serodiagnosis of TB infection.

PMID- 17519102
TI  - Evaluation of the resazurin assay for the detection of multidrug-resistant
      Mycobacterium tuberculosis in Madagascar.
AB  - SETTING: Multidrug-resistant (MDR) tuberculosis (TB) can jeopardise the success
      of national TB control programmes. Rapid, simple drug susceptibility tests
      applicable in developing countries would allow earlier treatment of patients with
      MDR infections. OBJECTIVE: To test the feasibility and performance of the
      resazurin microtitre assay (REMA) as an indirect test for detecting isoniazid
      (INH) and rifampicin (RMP) resistance of Mycobacterium tuberculosis strains in
      Madagascar. DESIGN: Study comparing the sensitivity and specificity of the REMA
      plate test with the Lowenstein-Jensen proportion method for determining the
      resistance of M. tuberculosis strains to INH and RMP. RESULTS: The sensitivity
      and specificity of the resazurin test were studied in 77 strains and were
      respectively 95% and 97.3% for the detection of INH resistance, and 95% and 100%
      for the detection of RMP resistance. The sensitivity and specificity for the
      identification of MDR strains were respectively 89% and 100%. CONCLUSION: The
      resazurin test is sensitive and specific enough for the detection of INH- and RMP
      resistant strains. It is also easy to use, rapid and inexpensive, making it
      suitable for developing countries. Its usefulness for national drug resistance
      surveys should be assessed.

PMID- 17519103
TI  - Clinical features in secondary and cryptogenic organising pneumonia.
AB  - SETTING: The clinical differences between cryptogenic organising pneumonia (COP)
      and secondary organising pneumonia (OP) have not been studied well. OBJECTIVE: To
      compare clinical features in COP and secondary OP. DESIGN: Causes, clinical
      features, treatment, radiographic studies and pathology were studied. RESULTS:
      After re-evaluation, 104 patients fulfilled the diagnostic criteria, 58 for COP
      and 46 for secondary OP. The mean age was 68 years. Most of the patients were
      smokers (79/104). Infections were the most common causes of secondary OP (21/46).
      Cough was the most common symptom and crackles the most common sign. Crackles
      were more common in patients with secondary OP (P = 0.02). Transbronchial biopsy
      was the diagnostic test in 81/104 cases. Most patients had lowered partial oxygen
      pressure (PO(2)) and mildly restrictive spirometry, with no differences between
      the two groups. Radiographic features were similar. Corticosteroids were the
      treatment in 70% of the patients, but 27% received no pharmacological treatment.
      The average initial dose of steroids was 42 mg prednisolone, and was similar for
      both groups. Relapses were seen in 20% of cases, with no difference between the
      two groups. CONCLUSION: There were no major differences in clinical features of
      COP and secondary OP, except that crackles were more common in secondary OP.

PMID- 17519104
TI  - Reported prevalence and co-morbidity of asthma, chronic bronchitis and emphysema:
      a pan-European estimation.
AB  - OBJECTIVE: Comparable population-based data exist at the European level for
      asthma but not for chronic obstructive pulmonary disease. Data from the World
      Health Organization's Large Analysis and Review of European Housing and Health
      Status Study conducted in random samples from eight European cities were used 1)
      to describe the prevalence of chronic bronchitis and emphysema (CBE) and asthma
      according to socio-demography, addictions, physical activities and body mass
      index; and 2) to identify the co-morbidities of these respiratory diseases.
      DESIGN: A total of 6915 adults filled out a standardised questionnaire on health
      outcomes, including major respiratory diseases and individual characteristics.
      RESULTS: Data showed that in the year preceding the survey, 3.3% of individuals
      had been diagnosed or treated for asthma and 6.2% for CBE. One per cent suffered
      simultaneously from both. Large variations were observed between cities. Physical
      activities and never smoking were inversely associated with CBE, independently of
      socio-cultural differences between the eight cities. Furthermore, both asthma and
      CBE were significantly related to several non-respiratory diseases, after
      adjustment for potential confounders. CONCLUSION: Population-based data from
      eight European cities show that there is a link between chronic respiratory
      diseases and various non-respiratory co-morbidities that needs further
      investigation.

PMID- 17519105
TI  - Tuberculosis teaching in Brazilian medical schools.
AB  - To achieve tuberculosis (TB) control, National Tuberculosis Programme guidelines
      should be implemented effectively. In a survey conducted in 2005-2006, 33
      Brazilian medical school coordinators answered a questionnaire about TB
      education. The median time dedicated to TB was 27 h (4-119 h), spread over
      several disciplines, mainly biological and clinical. This included 12 h (0-88 h)
      of practical activities, mainly in university hospitals (53%). The recommendation
      to offer human immunodeficiency virus testing for TB patients was taught in only
      54% of the schools. TB education in Brazil is fragmented and restricted to a
      biological approach, while field activities are insufficient and carried out in
      inadequate settings. Important changes to the TB curriculum are necessary.

PMID- 17519106
TI  - Pregnancies complicated by multidrug-resistant tuberculosis and HIV co-infection
      in Durban, South Africa.
AB  - SETTING: Tertiary hospitals in KwaZulu Natal, South Africa. OBJECTIVE: To study
      the impact of multidrug-resistant tuberculosis (MDR-TB) and human
      immunodeficiency virus-1 (HIV-1) co-infection during pregnancy on maternal and
      perinatal outcome. DESIGN: Prospective study performed between 1996 and 2001.
      Symptomatic pregnant women were investigated for TB. Those with confirmed MDR-TB
      were reported on. RESULTS: Three of five pregnant women with MDR-TB were HIV-1 co
      infected. One woman decided to terminate the pregnancy and one experienced pre
      term labour. Two neonates had features of growth restriction. CONCLUSION:
      Management of pregnant women with MDR-TB in an HIV-endemic area is possible in
      developing countries.

PMID- 17519108
TI  - Current trends in nitric oxide research.
AB  - Nitric oxide (NO), a molecule with multidimensional effects has generated
      exponential amount of research since its identification as a biological messenger
      almost two decades back. The recent trend in NO research is to explore newer
      dimensions in the cellular and molecular mechanisms of actions and interactions
      of NO with various biomolecules and their implications in various
      pathophysiological states. Advances in our knowledge of the mechanisms by which
      this pleiotropic molecule regulates the expression of eukaryotic genes has
      generated considerable excitement and is paving the way for development of novel
      NO based therapeutic strategies. However, it is still a challenge to understand
      fully the paradox of beneficial and damaging effects of this exciting molecule.
      This review will discuss the current trends of research in this area especially
      highlighting the new insights gained from recent experimental and clinical
      studies. New approaches to reduce or augment the availability of NO to benefit a
      wide range of clinical conditions and avenues for future research are also
      briefly discussed.

PMID- 17519109
TI  - Phenylpropanoids as naturally occurring antioxidants: from plant defense to human
      health.
AB  - Phenylpropanoids (PPs) belong to the largest group of secondary metabolites
      produced by plants, mainly, in response to biotic or abiotic stresses such as
      infections, wounding, UV irradiation, exposure to ozone, pollutants, and other
      hostile environmental conditions. It is thought that the molecular basis for the
      protective action of phenylpropanoids in plants is their antioxidant and free
      radical scavenging properties. These numerous phenolic compounds are major
      biologically active components of human diet, spices, aromas, wines, beer,
      essential oils, propolis, and traditional medicine. Last few years, much interest
      has been attracted to natural and synthetic phenylpropanoids for medicinal use as
      antioxidant, UV screens, anticancer, anti-virus, anti-inflammatory, wound
      healing, and antibacterial agents. They are of great interest for cosmetic and
      perfume industries as active natural ingredients. In the present review, the
      metabolic pathways of phenylpropanoid biosynthesis in plants and the mechanism of
      phenylpropanoid-mediated plant defense are described. Learning from plants, free
      radical-driven, molecular and cellular processes modulated by phenylpropanoids in
      human cell cultures in vitro and in the in vivo animal models of tumors,
      inflammation, and cellular damage are also reviewed.

PMID- 17519110
TI  - Arsenic and lead induced free radical generation and their reversibility
      following chelation.
AB  - Health hazards caused by heavy metals have become a great concern to the
      population. Lead and arsenic are one of the most important current global
      environmental toxicants. Their toxic manifestations are being considered caused
      primarily due to the imbalance between pro-oxidant and antioxidant homeostasis
      and also due to a high affinity of these metals for thiol groups on functional
      proteins. They also interfere with a number of other body functions and are known
      to affect central nervous system (CNS), hematopoietic system, liver and kidneys
      and produce serious disorders. They produce both acute and chronic poisoning, of
      which chronic poisoning is more dangerous as its very difficult to revert back to
      normal condition after chronic exposure to these insidious metals present in our
      life. Despite many years of research, we are still far from an effective
      treatment of chronic plumbism and arsenicosis. Current approved treatment lies in
      the administration of chelating agents that forms an insoluble complex with the
      metal and removes it. They have been used clinically as antidotes for treating
      acute and chronic poisoning. The most widely used chelating agents are calcium
      disodium ethylenediamine tetra acetic acid (CaNa2EDTA), D-penicillamine and
      British anti-lewisite (BAL). Meso 2,3 dimercaptosuccinic acid (DMSA), an analogue
      of BAL, has been tried successfully in animals as well as in humans. But it is
      unable to remove the metal from intracellular sites. Effective chelation therapy
      for intoxication by heavy metals depends on whether the chelating agents are able
      to reach the intracellular site where the heavy metal is firmly bound. One of the
      important approaches has been the use of combination therapy. This includes use
      of structurally different chelators or a combination of an adjuvant/ antioxidant/
      herbal extracts and a chelator to provide better clinical/ biochemical recovery.
      A number of other strategies have been suggested to minimize the numerous
      problems. This article presents the recent development made in this area with
      possible directions for future research.

PMID- 17519111
TI  - Attenuation of 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine induced
      nigrostriatal toxicity in mice by N-acetyl cysteine.
AB  - The present study was designed to investigate the effects of N-acetyl cysteine
      (NAC), an antioxidant on 1-methyl 4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)
      induced neurotoxicity in the nigrostriatal dopaminergic system of mice. MPTP
      treatment caused 80% decrease of the dopamine levels in the striatum of C57BL/ 6J
      mice. A marked increase in the extent of lipid peroxidation, superoxide dismutase
      (SOD) and g-glutamyl transpeptidase (g-GTP) was seen, while a significant
      decrease in the levels of glutathione (GSH), total thiols and glutathione
      peroxidase (GPx) activity was observed in the substantia nigra pars compacta
      (SNpc) of MPTP treated animals. As compared to control animals, Co-administration
      of NAC with MPTP restored the depleted dopamine, GSH, total tissue thiol levels
      and GPx activity in SNpc of treated mice brain. Moreover, NAC treatment also
      provided protection against lipid peroxidation and superoxide dismutase activity.
      The results of present study suggested that NAC attenuates MPTP neurotoxicity in
      mice brain and this protection by the NAC might be contributing to the
      regeneration of GSH, a major antioxidant.

PMID- 17519112
TI  - Manipulation of energy and redox states in the C6 glioma cells by buthionine
      sulfoxamine and N-acetylcysteine and the effect on cell survival to cadmium
      toxicity.
AB  - Changes in cellular energy and redox states were studied in the C6 glioma cells
      following exposure to chemicals that affect glutathione metabolism. It was
      demonstrated that treatment with sublethal concentrations (25, 50 and 100 microM)
      of buthionine sulfoxamine (BSO) did not affect cellular energy state as measured
      by total adenosine nucleotides (TAN=ATP+ADP+ AMP), ATP:ADP:AMP and energy charge
      potential (ECP=[ATP + 0.5 (ADP)]/TAN). However, there was a significantly
      decrease in cellular GSH/GSSG and total glutathione (TG=[GSH+GSSG]/ TAN). The
      change was due to a significant decrease in intracellular GSH level without
      significant change in [GSSG]. Cells exposed to BSO for 24 hr were much more
      sensitive to subsequent injuries caused by Cd (0.6 mM for 3 hr). The results
      indicated that while a significant reduction of intracellular redox state did not
      affect cell viability, it could increase the susceptibility of cells to
      subsequent chemical stress. N-acetylcysteine (NAC), on the other hand, caused a
      dose (1, 5 and 10 mM)-dependent increase in GSH/GSSG without significant changes
      in intracellular energy state. Improvement of intracellular GSH/GSSG offered no
      protection against subsequent Cd induced cell death unless NAC was present at the
      time Cd was added. The pattern of cell death also correlated with the increase in
      intracellular free radial generation as measured by the fluorescence labeling
      with 27- dichlorofluorescin. Results of the present study demonstrated that
      intracellular redox states could be manipulated by addition of chemicals that
      affect glutathione metabolism. While the redox state may not be the sufficient
      condition to cause cell death, it could modulate the response of cells to
      subsequent Cd treatment. Furthermore, the action of NAC against Cd cytotoxicity
      may not be related to intracellular redox status.

PMID- 17519113
TI  - Metal complexes of dietary flavonoids: evaluation of radical scavenger properties
      and protective activity against oxidative stress in vivo.
AB  - Interaction of certain flavonoids with transition metals increases their water
      solubility and leads to the formation of flavonoid-metal complexes, which may act
      as superoxide dismutase mimics with high scavenger potencies toward superoxide.
      Effect of serum albumin on stability of flavonoid-metal complexes was studied and
      complex of rutin with iron (II) was found to be the most stable. The ability of
      flavonoid metal complexes to catalyze homolytic cleavage of hydrogen peroxide was
      also studied and rutin iron (II) complex was found to be relatively poor Fenton
      catalyst. The potential therapeutic benefits of this new antioxidant agent were
      studied using experimental model of pathological states associated with oxidative
      stress in vivo. Acute hepatic injury in MT-I/MT-II null transgenic mice induced
      by injections of thioacetamide was used for this purpose. It was found that
      pretreatment with rutin- iron complex protected against thioacetamide induced
      hepatotoxicity as observed by a significant reduction in the elevated levels of
      serum enzymes and partial normalization of GSH/GSSG ratio, glutathione peroxidase
      II and glutathione reductase activity in mice liver. The results demonstrate that
      flavonoid-metal complexes possess effective free radical scavenger ability and
      have potent therapeutic benefits for the treatment of oxidative stress-related
      diseases and dysfunction.

PMID- 17519115
TI  - Anionic currents in hypoxia-mediated cardiac toxicity: a computer study.
AB  - Hypoxia-caused modulation of cardiac electrophysiology was modeled by computer
      simulation. Emphasis was on the effect of activation of anionic channels on the
      electrical state of the tissue. The model includes implicitly the effect of the
      presence of reactive oxygen species (ROS) and nitrogen oxide (NO) on myocyte
      membrane voltage by their contribution to the activation of chloride currents.
      Three anionic currents were added to the modified Luo-Rudy ionic model of the
      ventricular action potential used in these calculations. The effect of the
      activation of the usually dormant currents due to hypoxia results in the
      modulation of the morphology of the action potential and the ECG. Transition of
      the ECG to ventricular fibrillation is shown. An important finding reported here
      is that control of the swelling and protein kinase C (PKC)-activated chloride
      currents can limit the electrical chaos of pharmacologically-caused hypoxic
      cardiac toxicity.

PMID- 17519114
TI  - Vascular endothelial oxidative stress in alcohol-induced hypertension.
AB  - Epidemiological studies in humans and experimental studies in animals have shown
      the link between chronic alcohol consumption and the prevalence of hypertension.
      However, molecular mechanisms implicated with alcohol-induced increases in blood
      pressure (BP) remain elusive. The objective of this study was to investigate the
      relationship between BP and molecular as well as physiological changes in aortic
      endothelium in chronic ethanol treated rats. Male Fisher rats were given 20%
      ethanol (4 g/kg) orally and controls received 5% sucrose daily for 12 weeks. The
      BP was recorded weekly by tail-cuff method and after 12 weeks, rats were
      anesthetized with pentobarbital, thoracic aorta isolated and used for aortic
      reactivity using tissue bath and for biochemical analysis. The data show that
      ethanol ingestion significantly increased systolic, diastolic and mean BP after
      12 weeks compared to control. The endothelial nitric oxide synthase (eNOS) and
      vascular endothelial growth factor (VEGF) expressions were down-regulated leading
      to depletion of aortic NO levels in ethanol treated rats compared to control. The
      aortic NADPH oxidase activity significantly enhanced with a concomitant increase
      in membrane lipid peroxidation and depressed ratio of reduced to oxidized
      glutathione in alcohol-treated rats compared to control. The aortic
      vasoconstriction was slightly enhanced in response to phenylephrine but
      vasorelaxation was significantly diminished in response to acetylcholine,
      adenosine and sodium nitroprusside in chronic ethanol treated rats. It is
      concluded that chronic ethanol ingestion induces aortic endothelial oxidative
      injury and the down regulation of nitric oxide generating system leading to
      impaired vasorelaxation and hypertension in rats.

PMID- 17519116
TI  - Biochemical and molecular evaluation of neutrophil NOS in spontaneously
      hypertensive rats.
AB  - Resting neutrophils generate NO, while activation leads to the production of
      reactive oxygen and nitrogen species. Nowadays cardiovascular pathological
      conditions such as hypertension, cardiac ischemia, reperfusion and heart failure
      are associated with inflammation. This project explores the respiratory burst
      potential and NO generation status in the neutrophils, plasma, aorta, and kidneys
      from normotensive Wistar and spontaneously hypertensive rats (SHR). Total and
      protein associated nitrite content was quantitated using Griess reagent following
      cadmium reduction and mercuric chloride treatment respectively. NO and superoxide
      generation evaluated by Flowcytometry and peroxynitrite by spectrofluorimetric
      method. Expression of NOS isoforms was analyzed by RT-PCR. NO generation from SHR
      neutrophils was significantly augmented in comparison to normotensive
      counterparts. Neutrophils activated in response to arachidonic acid, PMA, fMLP or
      E. coli generated more superoxide radicals among SHR, and consequentially
      peroxynitrite. Expression of iNOS was significantly more in the SHR neutrophils,
      while that of nNOS remained unaffected. Results suggest that NO generated in SHR
      is utilized in scavenging superoxide radicals thereby limiting its
      bioavailability. Thus induction of NOS in neutrophils combined with augmented
      oxidative stress might influence its association with endothelium and contribute
      to inflammatory responses under hypertensive condition.

PMID- 17519117
TI  - Beneficial effects of pro-/antioxidant-based nutraceuticals in the skin
      rejuvenation techniques.
AB  - Modern technologies of skin rejuvenation include many physical and chemical
      intervention tools--laser irradiation, oxygen and ozone therapy, chemical peels,
      plastic surgery operations--affecting by different mechanisms the sensitive
      physiological free radical/antioxidant balance in the skin. All these
      interventions induce from mild to severe tissue damage, providing beneficial
      biochemical stimuli for skin re-epithelization and rejuvenation. Paradoxically,
      free radical production in the course of tissue inflammation helps to combat free
      radical damage consequent to the ageing process. We have studied two animal
      models (experimental burn and trichloracetic peeling), reproducing on the Wistar
      rat the effects generated by the commonly practiced aesthetic medicine procedures
      of laser resurfacing and chemical peels, demonstrating that the severe oxidative
      stress induced both systemically and on skin can be modulated by the oral pre-
      and post treatment administration of specific nutraceutical formulations. Potent
      antioxidants (RRR-alpha-tocopherol, coenzyme Q10), enhancing antioxidant
      defences, coupled with mild pro-oxidants, enhancers of a specific immune defense
      (soy phospholipids, L-methionine), at the blood and the skin levels, proved in
      fact to be beneficial in vivo, on the rat, for skin healing, trophism and
      accelerated re-epithelization. Data obtained allow us to predict the possibility
      of innovative protocols for dermocosmetology, enabling successful lowering of the
      risk of permanent adverse effects, and prolonging the duration of the beneficial
      effects of dermocosmetologic procedures.

PMID- 17519118
TI  - Isoniazid induces oxidative stress, mitochondrial dysfunction and apoptosis in
      Hep G2 cells.
AB  - Isoniazid (INH) continues to be a sheet anchor in treatment of tuberculosis,
      however its chronic administration is known to cause hepatotoxicity through a
      poorly defined mechanism. Ellucidation of mechanism underlying INH induced
      hepatotoxicity may be beneficial in devising ways to counteract toxic
      manifestations. In view of this concentration dependent effects INH were
      evaluated in hepatoma cell line (Hep-G2). INH exposure produced cytotoxic effects
      in Hep-G2 cells in a characteristic dose dependent manner. There was considerable
      cell detachment, loss of viability and alterations in cellular morphology that
      were indicative of toxic insult. We observed cell shrinkage at highest
      concentrations (88 microM) suggesting an involvement of apoptosis. This finding
      was substantiated by the flow cytometry data and DNA fragmentation analysis which
      clearly indicated that INH induced cytotoxicity, was being mediated by induction
      of apoptosis. Furthermore there was mitochondrial dysfunction as indicated by
      significant inhibition of MTT Reduction as compared to control at all the
      concentrations and depletion of cellular glutathione (GSH) content along with
      increased production of Reactive oxygen species (ROS). Collectively these
      findings led us to conclude that INH induced apoptosis in Hep-G2 cells is
      mediated by generation of oxidative stress.

PMID- 17519119
TI  - Blood pressure control and therapeutic modulation of the adrenergic overdrive.

PMID- 17519120
TI  - How "pre" is prehypertension?

PMID- 17519121
TI  - Analysis of antihypertensive effects of statins.
AB  - Hypertension and hyperlipidemia, two powerful risk factors of cardiovascular
      disease (CVD), often coexist. Therefore, treatment should consider the beneficial
      properties of drugs used to treat either condition. Statins, the mainstay of
      lipid-lowering therapy, result in a significant clinical benefit both in primary
      and secondary CVD prevention. In addition to their hypolipidemic capacity, other
      properties may contribute to statin-induced benefits. Clinical and experimental
      evidence indicates that statins may modulate blood pressure (BP). The mechanisms
      by which statins reduce BP seem to be largely independent of their lipid effects.
      Although small, reductions in BP are possibly clinically relevant. Large landmark
      studies confirm that statins can reduce CVD risk in hypertensive patients. These
      findings suggest that statins could be prescribed as an adjunct in treating
      hypertension with dyslipidemia or even in patients with "normal" cholesterol
      levels. Whether the effect of statins on BP is accompanied by an additional
      decrease in clinical outcomes needs to be investigated in long-term, large-scale
      trials.

PMID- 17519122
TI  - Compliance and fixed-dose combination therapy.
AB  - Despite data on the importance of blood pressure control in preventing
      cardiovascular and cerebrovascular events, only 34% of hypertensive patients have
      their blood pressure under control. The National Council on Patient Information
      and Education has estimated that the compliance rate is just over 30% for chronic
      conditions like hypertension. Polypharmacy and complex treatment regimens have
      been identified as important, modifiable risk factors for medication
      noncompliance. Fixed-dose combination regimens are attractive options because of
      the improved antihypertensive efficacy resulting from the dual mechanistic action
      of components targeting different effector mechanisms. One drug in the fixed-dose
      combination may negate an adverse effect of the other medication. Above all,
      fixed-dose combination therapy reduces pill burden and improves medication
      compliance, which can translate into better cardiovascular outcomes. Fixed-dose
      combinations should be used routinely for the management of hypertension and
      should also be considered when initiating therapy for patients with newly
      diagnosed hypertension.

PMID- 17519123
TI  - How to treat hypertension in patients with peripheral artery disease.
AB  - The risk of peripheral artery disease is underestimated by many physicians; such
      risk is further augmented by the presence of hypertension. Detection of these
      conditions is essential to prevent cardiovascular accidents. This review deals
      with the management of peripheral artery disease as a risk factor, highlighting
      the need for triple therapy (antiplatelet drugs, angiotensin-converting enzyme
      inhibitors, and statins). Treatment of hypertension is approached by reviewing
      the essentials of the different antihypertensive drugs available, focusing on
      their peripheral circulatory effect. However, because individual antihypertensive
      drugs seem not to differ largely in this respect, attention is drawn to the
      message that the most important task in these patients is to control total
      cardiovascular risk rather than focusing on the choice of the individual
      antihypertensive drug.

PMID- 17519124
TI  - The relationship between "race" and genetics in biomedical research.
AB  - The post-human genome sequencing era has presented several daunting challenges
      for biomedical research. How do we begin to quantify the level of sequence
      variation that exists within and between human populations? This challenge has
      serious implications for the enigma called "race," genetic ancestry, group
      definition, and membership. Another challenge has been the attempt to understand
      the role DNA sequence variation contributes to variation in susceptibility to
      common complex diseases. How these challenges are met will have an impact on our
      ability to determine if health disparities (eg, cardiovascular disease) are due
      to biological differences. Here we discuss genetic variation among African
      Americans and Hispanic Americans and its implications for "race." We believe that
      the casual use of "race" to define groups in biomedical research has contributed
      to our limited understanding of complex disease etiology and risk factors driving
      health disparities.

PMID- 17519125
TI  - Should the results of TROPHY affect the JNC 7 definition of prehypertension?
AB  - In the Trial of Preventing Hypertension (TROPHY), volunteers with "high normal
      blood pressure" were randomized to 4 years of placebo (n = 381) or 2 years of 16
      mg/d of candesartan (n = 391) followed by 2 years of placebo. At 2 years, there
      was a 26.8% absolute and a 66.3% relative risk reduction (P < 0.0001) of
      hypertension in the candesartan group. At study end, the former candesartan group
      had a 9.8% absolute and a 15.6% relative risk reduction (P < 0.007) of
      hypertension. The treatment was well tolerated. The Seventh Joint National
      Committee (JNC 7) changed the nomenclature from "high normal blood pressure" to
      "prehypertension" and widened the range to 120 to 139 and/or 80 to 89 mm Hg. Our
      results support the term "prehypertension" only for the 130 to 139 and/or 85 to
      89 mm Hg group; in 4 years two thirds of the placebo group developed
      hypertension. We suggest stratifying the JNC classification into
      "prehypertension" (130-139 and/or 85-89 mm Hg) and "high normal blood pressure"
      (120-129 and/or 80-84 mm Hg). By the present JNC definition, only one quarter of
      adult men have normal blood pressure. Removing the disease label from another 28%
      would appropriately focus attention on high-risk prehypertension.

PMID- 17519126
TI  - Antihypertensive effects of drospirenone and 17beta-estradiol in hypertensive
      postmenopausal women.

PMID- 17519127
TI  - Are current guidelines optimal for treatment of blood pressure in patients with
      coronary artery disease?

PMID- 17519128
TI  - The NTS and integration of cardiovascular control during exercise in normotensive
      and hypertensive individuals.
AB  - Due to upward resetting of baroreceptors, tachycardia coexists with increased
      pressure during dynamic exercise. This review critically evaluates current
      knowledge of proposed mechanisms to explain the continuous resetting of
      baroreflex control of heart rate and sympathetic nerve activity during and after
      exercise and exercise training. Of interest is the exercise-induced upward
      resetting that occurs in hypertensive and normotensive individuals. Accumulated
      evidence indicates that not only somatosensory afferents, but also inputs from
      central command projecting to the nucleus tractus solitarius (NTS) in the dorsal
      brainstem may mediate inhibition of excitatory neurotransmission on barosensitive
      neurons. Specific coordinated activation of vasopressinergic and oxytocinergic
      projections to the NTS is essential to tonically maintain baroreflex sensitivity
      and to adjust heart rate and cardiac output to circulatory demand at rest and
      during exercise in both sedentary and trained individuals. These findings
      reinforce the paramount importance of the NTS in integration of cardiovascular
      control during exercise.

PMID- 17519129
TI  - Cardiovascular effects of angiotensin II in the rostral ventrolateral medulla:
      the push-pull hypothesis.
AB  - Neurons within the rostral ventrolateral medulla (RVLM) play a pivotal role in
      the tonic and phasic control of blood pressure. This region also contains a high
      density of angiotensin II type 1 (AT1) receptors. There is evidence that tonic
      activation of AT1 receptors in the RVLM contributes to an increased sympathetic
      vasomotor activity in some models of hypertension. At the same time, under
      certain conditions, activation of AT1 receptors in the RVLM can cause
      sympathoinhibition. In this review we argue that the effect of endogenous
      angiotensin II in the RVLM on sympathetic vasomotor activity depends upon the
      balance between tonic excitatory and inhibitory effects on sympathetic premotor
      neurons mediated by AT1 receptors within this region, and that this balance may
      be altered in different physiological or pathophysiological conditions.

PMID- 17519130
TI  - Circulating angiotensin II and dietary salt: converging signals for neurogenic
      hypertension.
AB  - Circulating angiotensin II (Ang II) combined with high salt intake increases
      sympathetic nerve activity (SNA) in some forms of hypertension. Ang II-induced
      increases in SNA are modest, delayed, and specific to certain vascular beds. The
      brain targets for circulating Ang II are neurons in the area postrema (AP),
      subfornical organ (SFO), and possibly other circumventricular organs. Ang II
      signaling is integrated with sodium-sensitive neurons in the SFO and/or organum
      vasculosum of the lamina terminalis (OVLT) and drives sympathetic premotor
      neurons in the rostral ventrolateral medulla (RVLM) via the paraventricular
      nucleus (PVN). It is likely that, over time, new patterns of gene expression
      emerge within neurons of the SFO-PVN-RVLM pathway that transform their signaling
      properties. This transformation is critical in maintaining increased SNA.
      Identification of a novel gene supporting this process may provide new targets
      for treatment of neurogenic hypertension.

PMID- 17519131
TI  - New insights into the electrophysiology of brainstem circuits controlling blood
      pressure.
AB  - The brainstem contains the necessary circuitry for the maintenance and regulation
      of arterial blood pressure. It has become increasingly clear in the past few
      years that the characteristics of the neurons that constitute these circuits are
      not static, but can be altered in the face of chronic changes in physiological
      state. Alterations in voltage-gated and ligand-gated ion channels have been
      reported in neurons located within the nucleus of the solitary tract and the
      nucleus ambiguus in response to hypertension and exposures to hypoxia and
      environmental pollutants (eg, ozone and cigarette smoke). A discussion of these
      neuronal adaptations, the mechanisms that might initiate and sustain the
      adaptations, and their potential significance is the focus of this brief review.

PMID- 17519133
TI  - [Should we be paying attention to inspiratory capacity? ].

PMID- 17519134
TI  - [Development of a questionnaire to measure asthmatic patients' knowledge of their
      disease].
AB  - OBJECTIVE: To develop a valid, reliable, and sensitive self-administered
      questionnaire in Spanish to measure the knowledge asthmatic patients have of
      their disease. PATIENTS AND METHODS: The face and content validity of the
      questions was established by consensus among expert pulmonologists. To determine
      the importance of the questions, they were put to 100 participating asthmatic
      patients. The number of questions was reduced by consensus taking into account
      the importance given to each question by these patients. A further 25 patients
      participated in the assessment of reliability and sensitivity. The questionnaire
      was administered 5 times: twice before and 3 times after an educational
      intervention. The direct and indirect external consistency (kappa statistic) and
      the overall kappa value were determined. Sensitivity was assessed from the number
      of correct answers before and after the intervention (Wilcoxon test; P< .05) and
      from the percentage change (>40% was clinically significant). RESULTS: Fifty-nine
      questions were drawn up and the final version included 20. The test-retest
      consistency was between 0.81 and 1 in 76% of the cases before the intervention
      and in 92% after it. The kappa statistic before the intervention was between 0.41
      and 1 in 96% of the cases, and between 0.81 and 1 in 88% afterwards. The overall
      kappa values before and after the intervention were 0.12 and 0.43, respectively.
      The median sensitivity, measured as percentage change, was 67% and 10 patients
      showed an improvement between 81% and 233%. CONCLUSIONS: The questionnaire is
      reliable, has face and content validity, and is very sensitive to change. In view
      of these results, this instrument is useful for measuring the knowledge that
      asthmatic patients have of their disease in clinical practice and investigation.

PMID- 17519132
TI  - Vascular-brain signaling in hypertension: role of angiotensin II and nitric
      oxide.
AB  - Paracrine signaling by nitric oxide (NO) released from microvasculature within
      the brain affects multiple neuronal functions. Reviewed here is a role in central
      cardiovascular control. Within the nucleus tractus solitarii (NTS), a major
      regulatory region for arterial pressure, angiotensin II stimulates NO generation
      from endothelial nitric oxide synthase (eNOS). This enhances c-aminobutyric acid
      release to depress baroreflex function. In the spontaneously hypertensive rat
      (SHR), eNOS mRNA in the NTS is elevated compared to normotensive rats. Chronic
      inhibition of eNOS activity in the NTS of SHR reduced arterial pressure and
      increased baroreflex gain. Thus, eNOS-generated NO in the NTS plays a major role
      in control of baroreflex gain and arterial pressure. Indeed, its activity
      contributes to hypertension in the SHR. We propose that eNOS-generated NO in the
      SHR may be a compensatory mechanism for any potential threat to an adequate blood
      supply to the brain (eg, from genetically small arteries supplying the
      brainstem).

PMID- 17519135
TI  - [Spanish version of the Functional Outcomes of Sleep Questionnaire: scores of
      healthy individuals and of patients with sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: The main symptom of sleep apnea-hypopnea syndrome (SAHS) is excessive
      daytime sleepiness. The self-administered Functional Outcomes of Sleep
      Questionnaire (FOSQ) was designed to evaluate the impact of sleepiness on a
      patient's daily life. The aim of this study was to determine the scores of
      patients with SAHS and of healthy individuals on the Spanish version of the FOSQ
      and to assess its usefulness for evaluating the impact of excessive sleepiness in
      patients with suspected SAHS. POPULATION AND METHODS: Thirty-one patients with
      SAHS diagnosed by conventional polysomnography and 31 healthy individuals were
      included in the study. The following data were collected: patient information;
      use of tobacco, alcohol, or street drugs; blood pressure; and sleep schedule.
      Sleepiness was assessed on the Epworth Sleepiness Scale and the impact of
      sleepiness on activities of daily living by the FOSQ. RESULTS: Patients with SAHS
      (apnea-hypopnea index, 57) had a mean FOSQ total score of 88.7; healthy
      individuals had a mean score of 110.9 (P< .001) Significant differences were
      found between the 2 groups on all the FOSQ subscales, except for the one that
      measured social outcome. There was a moderate correlation between the 2
      questionnaires (r=--0.54; P=.01) and between FOSQ and the AHI (r=--0.39; P=.05).
      While the capacity to predict SAHS, based on receiver operating characteristic
      curves was greater for the Epworth Sleepiness Scale than for the FOSQ (area under
      the curve, 0.91 and 0.77, respectively), the diagnostic yield increased when both
      questionnaires were considered together. CONCLUSIONS: We obtained FOSQ reference
      scores for Spanish patients with SAHS and for healthy individuals. The study
      showed that the Spanish version of the FOSQ is a good instrument for assessing
      the impact of excessive sleepiness on activities of daily living in patients with
      suspected SAHS.

PMID- 17519136
TI  - [Impact of a rescue program on the operability of patients with bronchogenic
      carcinoma and chronic obstructive pulmonary disease].
AB  - OBJECTIVE: Bronchogenic carcinoma and chronic obstructive pulmonary disease
      (COPD) are strongly associated in our setting, occurring together in around 70%
      of cases. Approximately 60% of COPD patients who require resection for
      bronchogenic carcinoma are considered unfit for surgery because of seriously
      impaired lung function. The purpose of this study was to evaluate the extent to
      which a rescue program could improve lung function in COPD patients who had
      previously been considered unfit for surgery because of poor lung function.
      PATIENTS AND METHODS: The study enrolled COPD patients who had not been
      considered for surgical resection because they had a predicted postoperative
      forced expiratory volume in 1 second (FEV1) of less than 1 L. All of the patients
      participated in a 2-week rescue program that involved optimization of drug
      treatment (inhaled bronchodilators and/or corticosteroids) and intensive
      respiratory physiotherapy. Lung function was analyzed before and after the
      program. RESULTS: We evaluated 30 patients (26 men and 4 women) with a mean (SD)
      age of 66.7 (8.15) years and an initial FEV1 of 1.497 (0.27) mL (FEV1% of 55.7%
      [20.14%]). None of the patients had respiratory failure (PaO2 of 77.0 [9.4] mm Hg
      and PaCO2 of 41.6 [2.4] mm Hg). Twenty-four patients (80%) showed significant
      improvement in lung function (P< .001) after the program and were admitted for
      resection. Two wedge resections, 18 lobectomies, 2 pneumonectomies, and 2
      exploratory thoracotomies were performed (based on oncologic indications).
      Nineteen of the 24 patients who underwent surgery had no complications. Two
      patients had prolonged air leaks, 1 empyema, and 1 hemothorax. One patient died
      from sepsis. CONCLUSIONS: A large number (80%) of COPD patients previously
      considered unfit for surgical resection because of seriously impaired lung
      function can be admitted for surgery following an intensive drug and respiratory
      physiotherapy rescue program.

PMID- 17519137
TI  - [Noninvasive, indirect measurement of pulmonary artery pressure].
AB  - OBJECTIVE: The gold standard for measuring pulmonary artery pressure (PAP) is
      right heart catheterization. However, the usefulness of this technique is limited
      in patients with lung disease because of a poor acoustic window. The aim of this
      study was to assess PAP in a group of healthy persons using a noninvasive,
      indirect measurement procedure derived from the venous return flow velocity wave.
      MATERIAL AND METHODS: Twenty-three healthy volunteers with a mean (SD) age of 34
      (9) years were evaluated. Measurements were made with a Hitachi EUB 5000
      ultrasound device (3.5 MHz wave). The subject was placed in supine decubitus with
      neck hyperextended and head turned to one side. B-mode images were used to locate
      the point in the internal jugular vein 1 cm higher than its union with the
      subclavian vein. A color flow image was obtained of the vessel and a pulsed wave
      was then used to measure velocities. After 5 identical cycles, an estimate of PAP
      was derived from the ratio of maximum diastolic and systolic flow rates. RESULTS:
      On the right side, the mean (SD) ratio between flow rates was 0.50 (0.08),
      corresponding to a mean PAP of 15 (2.4) mm Hg. On the left side, the ratio was
      0.55 (0.09), corresponding to a mean PAP of 16 (2.8) mm Hg. The nonsignificant
      difference between mean PAP values on the right and left was 1.3 (3.1) mm Hg, and
      higher values were on the left. CONCLUSIONS: Mean PAP values obtained with the
      described procedure are within the normal range for a healthy population.
      Transcutaneous venous Doppler ultrasound is useful for estimating PAP in healthy
      individuals.

PMID- 17519138
TI  - [Clinical efficacy of sildenafil in patients with pulmonary hypertension in
      functional class II or III].
AB  - OBJECTIVE: To assess the efficacy of treatment with sildenafil monotherapy in
      patients with pulmonary hypertension. PATIENTS AND METHODS: An observational
      study was undertaken in 11 patients with pulmonary hypertension in functional
      class II or III who received treatment with sildenafil (150 mg/day). Seven of the
      patients had inoperable chronic thromboembolic pulmonary hypertension and 4 had
      pulmonary arterial hypertension. To assess treatment response, the following
      parameters were assessed during follow-up at 3, 6, and 12 months: exercise
      tolerance in the 6-minute walk test, change in functional class, and systolic
      pulmonary arterial pressure measured by echocardiography. RESULTS: We observed a
      significant improvement in exercise tolerance, as shown by increased 6-minute
      walk distance after 3, 6, and 12 months of treatment (increases of 20, 67, and 95
      m, respectively). All patients showed an improvement in functional class. The
      results of echocardiography did not reveal statistically significant differences
      in systolic pulmonary arterial pressure between baseline and 6 or 12 months of
      treatment. No significant adverse effects were observed, although sildenafil
      treatment was suspended in 1 patient due to persistent headache. CONCLUSIONS: The
      results of this study confirm that sildenafil is an effective drug for the
      management of pulmonary arterial hypertension and inoperable chronic
      thromboembolic pulmonary hypertension both in the short term and medium to long
      term, and that the drug is well tolerated and shows few side effects.

PMID- 17519139
TI  - [Influence of thoracentesis and pleural biopsy on biochemical parameters and
      cytology of pleural fluid].
AB  - OBJECTIVE: To assess the influence of thoracentesis and pleural biopsy on
      biochemical parameters and cytology of pleural fluid from patients with
      lymphocytic exudate. PATIENTS AND METHODS: A prospective, descriptive study was
      performed in 72 patients with pleural effusion who had lymphocytic exudate and in
      whom biopsy was indicated. Biochemical variables and cytology of pleural fluid
      were analyzed at baseline, 48 hours later (immediately prior to biopsy), and 48
      hours after biopsy. RESULTS: The patients had a mean (SD) age of 63 (17) years,
      57% were smokers, and 61% were men. Effusion was right-sided in 36% of patients,
      unilateral in 80%, and massive in 21%. The etiology was benign in 43 cases and
      neoplastic in 29 (40%). Pleural lactate dehydrogenase (LDH) was found to be
      increased following biopsy. This effect was significant in the overall population
      of 72 patients (649 [481] U/L just prior to biopsy and 736 [536] U/L 48 hours
      after biopsy; mean increase, 86 U/L; 95% confidence interval, 45-128 U/L; P<
      .001), in patients with pleural tumors (799 [529] U/L prior to biopsy and 957
      [571] U/L 48 hours later, P< .001), and in those with LDH concentration greater
      than 266 U/L. CONCLUSIONS: The results of our study show that a single
      thoracentesis procedure does not alter biochemical parameters or pleural cytology
      after 48 hours in lymphocytic exudates. Pleural needle biopsy leads to a
      significant increase in the concentration of LDH in patients with pleural tumors
      or higher baseline concentrations of LDH. Thoracentesis, pleural biopsy, or a
      combination of the two do not lead to significant changes in the number of
      eosinophils in pleural fluid.

PMID- 17519140
TI  - [Nutritional Status in COPD].
AB  - Changes in nutritional status, such as weight loss and malnutrition, are a very
      common complication in patients with chronic obstructive pulmonary disease
      (COPD). These changes primarily affect the patients' quality of life and
      functional capacity and they are also independent prognostic indicators of both
      morbidity and mortality. Malnutrition in these patients is due to multiple
      factors including increases in resting energy expenditure, decreased food intake,
      the effects of certain drugs, and, perhaps most importantly, a high systemic
      inflammatory response. The present review covers the most important facets of the
      prevalence, etiology, pathogenesis, and consequences of malnutrition in COPD and
      considers which parameters for nutritional assessment are the most satisfactory
      for use in routine clinical practice. The strategy used to ensure correct
      nutritional status in these patients is also discussed.

PMID- 17519141
TI  - [Severe obstructive sleep apnea syndrome in a toddler].
AB  - We report the case of a 3-year-old boy who had experienced intense snoring,
      frequent awakenings, intense respiratory effort during sleep, and delayed growth
      starting at the age of 15 months. He underwent adenoidectomy at 18 months.
      Symptoms initially improved but reappeared 3 months after surgery. He underwent a
      second adenoidectomy, this time with tonsillectomy, but there was no significant
      clinical improvement. Polysomnography revealed severe sleep apnea-hypopnea with
      an apnea-hypopnea index of 45. Continuous positive airway pressure improved sleep
      quality, although some symptoms, mainly snoring, persisted. A third adenoidectomy
      was necessary to normalize his breathing pattern during sleep.

PMID- 17519142
TI  - [Intrathoracic gossypiboma interpreted as bronchogenic carcinoma. Another false
      positive with positron emission tomography].
AB  - Gossypibomas from inflammatory reactions to textile foreign bodies are a rare
      postoperative complication and are easily confused with neoplastic processes
      because of their diversity of symptoms and radiographic signs. Positron emission
      tomography (PET) is seldom used to diagnose gossypibomas and PET findings can
      result in false positives for a diagnosis of neoplastic disease. We describe the
      case of a 56-year-old man in whom PET findings showed an intrathoracic mass
      suggesting a tumor. The final diagnosis was gossypiboma, identified 23 years
      after pneumothorax surgery.

PMID- 17519143
TI  - [Mediastinal parathyroid gland or adenopathy with endocrine cancer
      infiltration?].

PMID- 17519144
TI  - [Lady Windermere syndrome].

PMID- 17519145
TI  - Why we need to truly understand the medical literature.

PMID- 17519146
TI  - Biomarkers of semen in the vagina: applications in clinical trials of
      contraception and prevention of sexually transmitted pathogens including HIV.
AB  - Biomarkers of vaginal exposure to semen, long used in forensic medicine, are now
      becoming important in the development of vaginal microbicides to prevent HIV/STIs
      and the development of contraceptives. Semen biomarkers could help evaluate the
      safety of a new physical or chemical barrier, give preliminary indication of the
      effectiveness of physical barriers such as diaphragms or condoms, and provide
      information on unprotected intercourse among participants in a clinical trial who
      have been advised to use condoms. Candidate biomarkers of semen exposure fall
      into two broad categories: (1) biomarkers of seminal plasma, among which prostate
      specific antigen (PSA) is the best characterized; and (2) biomarkers of
      spermatozoa and other cells present in semen. This paper, authored by a working
      group of investigators performing research in the field of semen biomarkers,
      summarizes the characteristics of an ideal semen biomarker, reviews preclinical
      and clinical data on existing and potential biomarkers, and outlines the steps
      that should be carried out to develop an improved biomarker of semen exposure.

PMID- 17519147
TI  - The contraceptive vaginal ring compared with the combined oral contraceptive
      pill: a comprehensive review of randomized controlled trials.
AB  - BACKGROUND: The purpose of this review was to compare pharmacology, contraceptive
      efficacy, cycle control, side effects and acceptability with the combined
      contraceptive vaginal ring (CCVR) and combined oral contraceptives (COCs). STUDY
      DESIGN: All randomized controlled trials (RCTs) between the CCVR and a COC up to
      and including December 2006 were analyzed. RESULTS: Twelve RCTs comparing the
      CCVR and a COC were identified. Systemic exposure to ethinyl estradiol (EE) with
      the CCVR was half of that with a 30-microg EE-containing COC with less variation
      in serum levels. During CCVR use, sex hormone-binding globulin and cortisol
      binding globulin concentrations were significantly less increased than during COC
      use. Both methods showed adequate ovarian suppression and equal contraceptive
      efficacy. Uterine concentrations of EE and etonogestrel were not elevated with
      the CCVR. Cycle control achieved with the CCVR was better than that of the COC.
      Compliance with both methods was high. Mean blood pressure and body weight did
      not change in either group. Incidence of adverse events such as breast
      tenderness, headache and nausea was comparable, but a higher incidence of local
      and ring-related events led to higher discontinuation rates in the CCVR group.
      Both contraceptives were highly acceptable and resulted in a global improvement
      of sexual function. Ring users were more likely to continue with their method
      after study completion than COC users. CONCLUSIONS: The vaginal ring has the same
      contraceptive efficacy as COCs with lower systemic EE exposure, more consistent
      serum EE levels and better cycle control, but more local adverse events resulting
      in higher discontinuation rates.

PMID- 17519148
TI  - Comparison of the impact of vaginal and oral administration of combined hormonal
      contraceptives on hepatic proteins sensitive to estrogen.
AB  - OBJECTIVE: We evaluated the effects of a new combined hormonal contraceptive
      vaginal ring (CVR) delivering the nonandrogenic progestin Nestorone (NES) and
      ethinyl estradiol (EE) on several key estrogen-sensitive hepatic proteins that
      may be markers for the risk of arterial or venous disease events and on blood
      pressure (BP). Because the pharmacologic androgenicity of the progestin in these
      formulations influences the hepatic impact of EE, we selected an oral
      contraceptive (OC) delivering the androgenic progestin levonorgestrel (LNG) and
      EE as the comparator. We also investigated the effect of delivery route, which is
      known to modify the hepatic effects of estradiol, but has not been widely studied
      with EE. STUDY METHODS: Women, aged 18-34 years, with no contraindications to the
      use of combined OCs, were randomized to three cycles of treatment with a CVR
      delivering NES/EE (150/15 microg/day) or a combined OC providing LNG and EE
      (150/30 microg per tablet). Each cycle consisted of 21 days of active treatment,
      followed by 7 days without treatment. During the last weeks of the pretreatment
      and third treatment cycles, blood samples were obtained for determinations of
      plasma concentrations of angiotensinogen, an estrogen-sensitive hepatic protein,
      and serum concentrations of sex hormone-binding globulin (SHBG), total
      cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), triglycerides (TG) and estrogen- and androgen
      sensitive proteins. BP was also measured. RESULTS: Of 47 women randomized, 45
      completed the study (CVR: 23; OC: 22). Within-group comparisons over time by
      repeated-measure analysis of variance demonstrated statistically significant
      changes over time with both treatments for all hepatic proteins (p < .02) but not
      for TC. The within-group effects, presented as relative percent difference [95%
      confidence interval (CI)], were greatest for angiotensinogen [CVR: 227% (195
      262%); OC: 251.3% (218-288%)] and SHBG [CVR: 306% (237-389%); OC: 55% (30-86)].
      Both treatments were associated with small changes in systolic BP and diastolic
      BP (DBP), but only the within-group change in DBP for the OC group was
      statistically significant (p = .04). Between-treatment comparisons of third
      treatment cycle mean values were performed by analysis of covariance (baseline
      values as covariate). No statistically significant between-treatment differences
      were found for angiotensinogen, sensitive only to estrogen, or BP. Statistically
      significant treatment differences were found for all estrogen- and androgen
      sensitive proteins (p < or = .002) but not for TC. When presented as relative
      percent difference between the effects of treatment (CVR-OC/OC; 95% CI of percent
      difference), the difference was largest for SHBG (159% [117-210%]); smaller
      relative percent differences were found for HDL-C [31.9% (18.5-46.8%)], LDL-C
      [23.6% (33.4% to -2.4%)] and TG [39.0% (14.0-69.4%)], but not TC. CONCLUSION:
      Vaginal delivery of a combined hormonal contraceptive did not reduce the EE
      associated changes in estrogen-sensitive hepatic proteins observed after use of a
      combined OC. Significant treatment differences between the NES/EE CVR and the
      LNG/EE OC were found for SHBG, HDL-C, LDL-C, and TG, proteins sensitive to
      androgen as well as estrogen. No treatment difference was observed for
      angiotensinogen, which is sensitive only to estrogen. The observed treatment
      differences were therefore most likely due to the difference in androgenicity
      between NES and LNG.

PMID- 17519149
TI  - Bone mineral density in adolescents using norethisterone enanthate, depot
      medroxyprogesterone acetate or combined oral contraceptives for contraception.
AB  - PURPOSE: Most studies have shown a negative effect of depot-medroxyprogesterone
      acetate (DMPA) on the bone mineral density (BMD) of adolescents. There is no
      information available on the effect of norethisterone enanthate (NET-EN) on BMD
      in adolescents and the effect of combined oral contraceptives (COCs) on
      adolescent BMD is inconclusive. The aim of this longitudinal study was to
      investigate BMD in adolescent (aged 15-19 years) new users of hormonal
      contraception (DMPA, NET-EN and COCs). METHOD: New users of DMPA (n=115), NET-EN
      (n=115), COCs (n=116) and 144 nonuser controls were recruited. BMD was measured
      at the distal radius and midshaft of the ulna using dual X-ray absorptiometry.
      RESULTS: In total, 275 women were included in this interim analysis and total
      follow-up time was 553 person-years. There was no significant difference in
      radius BMD between users of different contraceptive methods at baseline (p=.40).
      Overall, an increase in radius BMD of 0.00522 per person-year was observed. This
      result was similar when adjusting for BMI in the random effects regression model
      (p=.88). The regression model showed that BMI was significantly associated with
      radius BMD, with each unit increase in BMI corresponding to an increase of 0.0029
      g/cm2 in BMD (95% CI 0.0023 to 0.0036, p<.001). Interaction between contraceptive
      method and follow-up time adjusted for BMI was not significant (p=.07). The
      increase in BMD for NET-EN users of 0.0013 g/cm2 per person-year (95% CI -0.0017
      to 0.0043) was significantly lower than that of nonusers (p=.017). For DMPA and
      COC users, the increase in BMD was not significantly different compared to the
      nonusers. This study suggests that NET-EN users had lower increase in BMD over
      time compared to the other user groups.

PMID- 17519150
TI  - Long-term assessment of symptomatology and satisfaction of an extended oral
      contraceptive regimen.
AB  - OBJECTIVE: The study was conducted to assess hormone withdrawal symptoms, patient
      acceptance and occurrence and management of bleeding with an extended oral
      contraceptive (OC) regimen. METHODS: Subjects were placed on an OC containing 3
      mg drosperinone (DRSP) and 30 microg ethinyl estradiol (EE), in the standard 21/7
      fashion for two cycles, before converting to an extended pattern of OC for women
      who indicated they had menstrually related symptoms such as headaches, cramping
      and mood swings (52 weeks with phone-call follow-up 6 months later). Daily
      assessments of bleeding, headache, pelvic pain, mood and number of pain pills
      were recorded. Results are reported as means with S.E., and values were compared
      using analysis of variance with Dunnett's post hoc test for comparison with 21/7
      cycle, Duncan's post hoc test for comparison of changes during the course of the
      extended regimen and Pearson's chi-square for comparison of proportions. RESULTS:
      Of the 111 women who began the extended OC regimen, 80 completed 1 year of use.
      Mood scores, headache scores and pelvic pain were all improved in the extended OC
      intervals, compared to the 21/7 cycle (p<.001 for all comparisons). Improvement
      in symptoms persisted throughout the 1 year extended regimen. The findings
      indicated that 53.7% of subjects had no breakthrough bleeding or breakthrough
      spotting (BTB/BTS) during any given 28-day interval of the extended regimen.
      BTB/BTS decreased in the second half compared to the first half of the extended
      regimen. To manage BTB/BTS, instituting a 3-day hormone-free interval (HFI) was
      significantly more effective than continuing OCs (p<.001). At the 6-month follow
      up, most subjects had continued the extended regimen on their own with a high
      level of satisfaction. CONCLUSIONS: An extended OC regimen containing DRSP/EE
      significantly improved mood, headaches and pelvic pain scores throughout the 1
      year of use, compared to a 21/7 cycle. Sustained BTB/BTS episodes occurred in 45
      subjects (56%), decreasing in the second half of the study and effectively
      managed with a 3-day HFI.

PMID- 17519151
TI  - Acceptability of contraceptive-induced amenorrhea in a racially diverse group of
      US women.
AB  - OBJECTIVE: The study was conducted to determine women's preferences about
      menstrual bleeding patterns and their willingness to manipulate bleeding with
      contraception. STUDY DESIGN: Women presenting for routine obstetric and
      gynecologic care at two US locations (Portland, OR, and Atlanta, GA) were offered
      a self-administered, anonymous survey. A validated survey tool was used. RESULTS:
      Valid surveys from 292 women were obtained. Mean age was 27 years (SD 8.0). We
      were unable to separate geographic vs. racial differences in responses because
      race significantly differed between sites (p<.001). The populations surveyed were
      predominantly black in Georgia (88%, 58/66) and white in Oregon (83%, 142/172).
      Overall, the majority of women did not like their menstrual period (69%, 190/275)
      and preferred a menstrual frequency of every 3 months or never (58%, 164/281)
      with no differences between racial groups. When asked if they would consider
      using a birth control method that stopped their menstrual periods, 40% (111/278)
      reported yes, 28% (78/278) reported no and 32% (89/278) were undecided. However,
      significantly fewer black than white women would consider a birth control method
      to stop their menstrual periods (29% vs. 49%, p=.006). CONCLUSIONS: Although the
      majority of US women surveyed dislike menstruation and prefer less frequent or no
      menstrual periods, black women were less accepting than white women of
      contraception that induces amenorrhea.

PMID- 17519152
TI  - Pharmacokinetic study to compare the absorption and tolerability of two doses of
      levonorgestrel following single vaginal administration of levonorgestrel in
      Carraguard gel: a new formulation for "dual protection" contraception.
AB  - OBJECTIVE: The study was conducted to assess levonorgestrel (LNG) serum levels
      achieved after a single administration of two different doses of Carraguard
      vaginal gel containing LNG (CARRA/LNG), designed for use as microbicide and
      contraceptive for potential dual protection. MATERIALS AND METHODS: This was a
      randomized double-blind pharmacokinetic study conducted in 12 subjects enrolled
      at two centers. Each subject received a single vaginal administration of
      CARRA/LNG containing either 0.75 or 1.5 mg LNG per 4 mL of gel on Days 10-12 of
      the menstrual cycle. LNG serum levels were measured at 0, 1, 2, 4, 8 and 12 h
      after administration and for the following 7 days. LH and progesterone (for a
      preliminary evaluation of effect on the ovarian function) as well as SHBG were
      measured in the daily samples. RESULTS: Serum LNG maximum concentrations (Cmax)
      were 14.1+/-2.1 and 11.7+/-2.7 nmol/L and Tmax was 12.0 and 6.0 h for the low and
      high dose, respectively, with large intersubject variability within the first 48
      h. Mean levels at 96 h were 10% of Cmax. Differences in AUC between both doses
      were not statistically significant. SHBG levels decreased approximately 25% by
      Day 4 after administration. Luteal activity was observed in 3/6 and 5/6 of the
      subjects in the low- and high-dose group, respectively. CONCLUSION: This study
      demonstrates that the CARRA/LNG gel can sustain elevated serum levels of the
      contraceptive steroid for up to 96 h after a single application. The serum levels
      attained with the 0.75-mg formulation are in the range expected to perturb the
      ovulatory process as observed in some subjects. The lack of correlation between
      the administered dose and serum concentrations of the steroid may be related to a
      rate-limiting absorption of LNG from the vaginal mucosa. The results reported
      here suggest that the CARRA/LNG formulation has good potential to become a dual
      protection method, possibly preventing conception and sexually transmitted
      infections.

PMID- 17519153
TI  - Injectable progestin contraceptive use and risk of HIV infection in a South
      African family planning cohort.
AB  - OBJECTIVE: To investigate whether the incidence of HIV infection is higher among
      sexually active women using depot medroxyprogesterone acetate (DMPA) or
      noresthisterone enanthate (NET-EN) injections for contraception than among women
      using nonhormonal or no contraception. METHODS: Five hundred and fifty-one
      initially HIV-negative women were followed up for a total of 491 person-years.
      Participants were interviewed, counselled, examined, tested for HIV and other
      STIs, and treated, at three monthly intervals for 1 year. RESULTS: There was no
      significant association between progestin contraceptive use and HIV infection
      (rate ratio 1.1, 95% CI 0.5 to 2.8; log-rank test, p=.73). In proportional
      hazards regression, the only significant hazard ratios for HIV acquisition were
      prevalent Neisseria gonorrhoea (5.2; 95% CI 1.1 to 23.7, p=.035) and Trichomonas
      vaginalis (4.8; 95% CI 1.0 to 22.8, p=.049); bacterial vaginosis was marginally
      significant (2.8; 95% CI 1.0 to 8.3, p=.057). The adjusted hazard ratios for NET
      EN and DMPA were 1.76 (95% CI 0.64 to 4.84) and 0.46 (95% CI 0.06 to 3.79),
      respectively, relative to nonuse. Five hundred and twelve of 551 women had one or
      more confirmed STIs during the study. CONCLUSIONS: There is no evidence of an
      association between HIV infection and injectable contraceptives. Due to the
      limited power of this study and because similar studies have not included young
      women using NET-EN, we recommend that further research be carried out to focus on
      the use of NET-EN and HIV acquisition in high risk groups.

PMID- 17519154
TI  - Contraceptive implants in Kenya: current status and future prospects.
AB  - BACKGROUND: Since introducing Norplant over 20 years ago in Kenya, demand for
      contraceptive implants has remained high and implant costs are dropping
      substantially. METHODS: An assessment of the Kenyan experience with implants was
      conducted to understand level of demand, capacity to provide services and
      reproductive health impact of possible increased use. Interviews were conducted
      with 35 key Kenyan informants. By modeling increases in national implant use (at
      the expense of oral contraceptives), reductions in the annual number of
      unintended pregnancies were estimated. RESULTS: Kenya has an unmet need for
      implants and the current network of trained providers appears ready to increase
      the volume of services. If 100,000 users of oral contraceptives switch to
      implants, then an estimated 26,000 unintended pregnancies can be averted over a 5
      year period. CONCLUSION: With increased purchases of implants by international
      donor agencies, Kenya can reduce reliance on short-term hormonal methods and
      reduce the 45% prevalence rate of unintended pregnancy.

PMID- 17519159
TI  - Microscope basics.

PMID- 17519155
TI  - Efficacy, acceptability and tolerability of the combined contraceptive ring,
      NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl
      estradiol and 3 mg of drospirenone.

PMID- 17519160
TI  - The optics of microscope image formation.

PMID- 17519161
TI  - Proper alignment of the microscope.

PMID- 17519162
TI  - Mating cameras to microscopes.

PMID- 17519163
TI  - Fundamentals of fluorescence and fluorescence microscopy.

PMID- 17519164
TI  - Fluorescent protein applications in microscopy.

PMID- 17519165
TI  - Live-cell fluorescence imaging.

PMID- 17519166
TI  - Working with classic video.

PMID- 17519167
TI  - Practical aspects of adjusting digital cameras.

PMID- 17519168
TI  - Cameras for digital microscopy.

PMID- 17519170
TI  - Electronic cameras for low-light microscopy.

PMID- 17519169
TI  - A high-resolution multimode digital microscope system.

PMID- 17519171
TI  - Camera technologies for low light imaging: overview and relative advantages.

PMID- 17519172
TI  - Digital manipulation of brightfield and fluorescence images: noise reduction,
      contrast enhancement, and feature extraction.

PMID- 17519173
TI  - Digital image files in light microscopy.

PMID- 17519174
TI  - High-resolution video-enhanced differential interference contrast light
      microscopy.

PMID- 17519175
TI  - Quantitative analysis of digital microscope images.

PMID- 17519176
TI  - Evaluating optical aberration using fluorescent microspheres: methods, analysis,
      and corrective actions.

PMID- 17519177
TI  - Ratio imaging: practical considerations for measuring intracellular Ca2+ and pH
      in living cells.

PMID- 17519178
TI  - Computational restoration of fluorescence images: noise reduction, deconvolution,
      and pattern recognition.

PMID- 17519179
TI  - Quantitative fluorescence microscopy and image deconvolution.

PMID- 17519180
TI  - Practical aspects of quantitative confocal microscopy.

PMID- 17519181
TI  - Theoretical principles and practical considerations for fluorescence resonance
      energy transfer microscopy.

PMID- 17519182
TI  - Fluorescence lifetime imaging microscopy.

PMID- 17519183
TI  - Fluorescence correlation spectroscopy: molecular complexing in solution and in
      living cells.

PMID- 17519184
TI  - Breaking the resolution limit in light microscopy.

PMID- 17519185
TI  - Virgin birth in a hammerhead shark.
AB  - Parthenogenesis has been documented in all major jawed vertebrate lineages except
      mammals and cartilaginous fishes (class Chondrichthyes: sharks, batoids and
      chimeras). Reports of captive female sharks giving birth despite being held in
      the extended absence of males have generally been ascribed to prior matings
      coupled with long-term sperm storage by the females. Here, we provide the first
      genetic evidence for chondrichthyan parthenogenesis, involving a hammerhead shark
      (Sphyrna tiburo). This finding also broadens the known occurrence of a specific
      type of asexual development (automictic parthenogenesis) among vertebrates,
      extending recently raised concerns about the potential negative effect of this
      type of facultative parthenogenesis on the genetic diversity of threatened
      vertebrate species.

PMID- 17519186
TI  - Twin intromittent organs of Drosophila for traumatic insemination.
AB  - In several animals, male genitalia create insemination wounds in areas outside
      the genital orifice of females. I report that such traumatic insemination (TI)
      occurs in the Drosophila bipectinata complex (Diptera: Drosophilidae) and
      illustrate a previously unknown evolutionary pathway for this behaviour. Flash
      fixation of mating pairs revealed the dual function of the paired claw-like basal
      processes, previously misidentified as a bifid aedeagus: (i) penetration of the
      female body wall near the genital orifice and (ii) sperm transfer into the
      genital tract through the wounds. Basal processes in closely related species
      (Drosophila ananassae and Drosophila pallidosa) also wounded females but did not
      transfer sperm; this represents a transitional state to TI as observed in the
      bipectinata complex. Copulatory wounding is suggested to occur in other allied
      species of the Drosophila melanogaster species group, including D. melanogaster.
      Ubiquitous sexual conflicts over mating may have led to the evolution of novel
      intromittent organs for insemination.

PMID- 17519187
TI  - Extreme environmental variation sharpens selection that drives the evolution of a
      mutualism.
AB  - The importance of infrequent events for both adaptive evolution and the evolution
      of species interactions is largely unknown. We investigated how the infrequent
      production of large seed crops (masting) of a bird-dispersed tree (whitebark
      pine, Pinus albicaulis) influenced phenotypic selection exerted by its primary
      avian seed predator-disperser, the Clark's nutcracker (Nucifraga columbiana).
      Selection was not evident during common years of low seed abundance, whereas it
      was replicated among areas and favoured traits facilitating seed dispersal during
      infrequent years of high seed abundance. Since nutcrackers act mostly as seed
      predators during small seed crops but as seed dispersers during the largest seed
      crops, trees experienced strong selection from nutcrackers only during infrequent
      years when the interaction was most strongly mutualistic. Infrequent events can
      thus be essential to both adaptive evolution and the evolutionary dynamics of
      species interactions.

PMID- 17519188
TI  - Floral reward production is timed by an insect pollinator.
AB  - Interval timing--sensitivity to elapsing durations--has recently been found to
      occur in an invertebrate pollinator, the bumble-bee (Bombus impatiens). Here,
      bumble-bees were required to time the interval between the start of foraging in a
      patch of low-quality artificial flowers providing 25% sucrose and the
      availability of a high-quality flower (HQF) that provided 50% sucrose after a
      fixed delay. The delay changed after every 20 foraging bouts in the order 30-150
      30 s. Bees visited the HQF sooner when the delay was 30 s than when it was 150 s,
      and visits to the HQF peaked near the end of both delays. When the delay changed
      to 150 s, bees appeared to time both the previous 30 s delay and the new delay.
      To examine whether bees also learned what kind of reward was provided at the HQF,
      its usual reward was replaced with 25% sucrose in a final foraging bout. Bumble
      bees rejected the HQF on the reward-replacement test. These results show that
      bumble-bees remembered both when reward was produced by the HQF and what type of
      reward was produced. These findings indicate that bumble-bees can learn both the
      timing and content of reward production.

PMID- 17519189
TI  - Do constructional constraints influence cichlid craniofacial diversification?
AB  - Constraints on form should determine how organisms diversify. Owing to
      competition for the limited space within the body, investment in adjacent
      structures may frequently represent an evolutionary compromise. For example,
      evolutionary trade-offs between eye size and jaw muscles in cichlid fish of the
      African great lakes are thought to represent a constructional constraint that
      influenced the diversification of these assemblages. To test the evolutionary
      independence of these structures in Lake Malawi cichlid fish, we measured the
      mass of the three major adductor mandibulae (AM) muscles and determined the eye
      volume in 41 species. Using both traditional and novel methodologies to control
      for resolved and unresolved phylogenetic relationships, we tested the
      evolutionary independence of these four structures. We found that evolutionary
      change in the AM muscles was positively correlated, suggesting that competition
      for space in the head has not influenced diversification among these jaw muscles.
      Furthermore, there was no negative relationship between change in total AM muscle
      mass and eye volume, indicating that there has been little effect of the
      evolution of eye size on AM evolution in Lake Malawi cichlids. The comparative
      approach used here should provide a robust method to test whether constructional
      constraints frequently limit phenotypic change in adaptive radiations.

PMID- 17519190
TI  - Generalization of learned predator recognition: an experimental test and
      framework for future studies.
AB  - While some prey species possess an innate recognition of their predators, others
      require learning to recognize their predators. The specific characteristics of
      the predators that prey learn and whether prey can generalize this learning to
      similar predatory threats have been virtually ignored. Here, we investigated
      whether fathead minnows that learned to chemically recognize a specific predator
      species as a threat has the ability to generalize their recognition to closely
      related predators. We found that minnows trained to recognize the odour of a lake
      trout as a threat (the reference predator) generalized their responses to brook
      trout (same genus as lake trout) and rainbow trout (same family), but did not
      generalize to a distantly related predatory pike or non-predatory suckers. We
      also found that the intensity of antipredator responses to the other species was
      correlated with the phylogenetic distance to the reference predator; minnows
      responded with a higher intensity response to brook trout than rainbow trout.
      This is the first study showing that prey have the ability to exhibit
      generalization of predator odour recognition. We discuss these results and
      provide a theoretical framework for future studies of generalization of predator
      recognition.

PMID- 17519191
TI  - Cooperation is less likely to evolve in a finite population with a highly skewed
      distribution of family size.
AB  - In the context of the finitely repeated Prisoner's Dilemma with the possibility
      of cooperating or defecting each time, the strategy tit-for-tat (TFT) consists in
      cooperating the first time and copying the strategy previously used by the
      opponent the next times. Assuming random pairwise interactions in a finite
      population of always defecting individuals, TFT can be favoured by selection to
      go to fixation following its introduction as a mutant strategy. We deduce the
      condition for this to be the case under weak selection in the framework of a
      general reproduction scheme in discrete time. In fact, we show when and why the
      one-third rule for the evolution of cooperation holds, and how it extends to a
      more general rule. The condition turns out to be more stringent when the numbers
      of descendants left by the individuals from one time-step to the next may
      substantially differ. This suggests that the evolution of cooperation is made
      more difficult in populations with a highly skewed distribution of family size.
      This is illustrated by two examples.

PMID- 17519192
TI  - An addendum to 'Songbird migration across the Sahara: the non-stop hypothesis
      rejected!'.

PMID- 17519193
TI  - Shell bone histology indicates terrestrial palaeoecology of basal turtles.
AB  - The palaeoecology of basal turtles from the Late Triassic was classically viewed
      as being semi-aquatic, similar to the lifestyle of modern snapping turtles.
      Lately, this view was questioned based on limb bone proportions, and a
      terrestrial palaeoecology was suggested for the turtle stem. Here, we present
      independent shell bone microstructural evidence for a terrestrial habitat of the
      oldest and basal most well-known turtles, i.e. the Upper Triassic Proterochersis
      robusta and Proganochelys quenstedti. Comparison of their shell bone histology
      with that of extant turtles preferring either aquatic habitats or terrestrial
      habitats clearly reveals congruence with terrestrial turtle taxa. Similarities in
      the shell bones of these turtles are a diploe structure with well-developed
      external and internal cortices, weak vascularization of the compact bone layers
      and a dense nature of the interior cancellous bone with overall short trabeculae.
      On the other hand, 'aquatic' turtles tend to reduce cortical bone layers, while
      increasing overall vascularization of the bone tissue. In contrast to the study
      of limb bone proportions, the present study is independent from the uncommon
      preservation of appendicular skeletal elements in fossil turtles, enabling the
      palaeoecological study of a much broader range of incompletely known turtle taxa
      in the fossil record.

PMID- 17519194
TI  - Phenotypic determinants of individual fitness in female fur seals: larger is
      better.
AB  - Inter-individual differences in fitness in female vertebrates have often been
      related to phenotypic discrepancies, suggesting that bigger individuals exhibit
      greater fitness. However, the use of the temporally variable indices of quality,
      such as body mass/condition, may not represent the most reliable index over
      longer time intervals. Few studies have assessed the direct influence of body
      size (BS) on individual fitness. We addressed this knowledge gap using data from
      long-term monitoring of individually marked female subantarctic fur seals. The
      females of higher quality (i.e. higher lifetime reproductive success) were larger
      in BS than their counterparts, which correlated with their ability to provision
      their pup with greater and more regular energy supply, possibly through the
      maximization of foraging performance and body fat storage. We accordingly found
      that our study population could be divided into three contrasted categories of
      maternal quality, with 33% of the females producing over 71% of the viable
      offspring constituting the next generation. We suggest that a larger BS
      represents a crucial selective advantage for a central place forager, especially
      when exploiting remotely available resources.

PMID- 17519195
TI  - Computational fluid dynamics for turbomachinery internal air systems.
AB  - Considerable progress in development and application of computational fluid
      dynamics (CFD) for aeroengine internal flow systems has been made in recent
      years. CFD is regularly used in industry for assessment of air systems, and the
      performance of CFD for basic axisymmetric rotor/rotor and stator/rotor disc
      cavities with radial throughflow is largely understood and documented.
      Incorporation of three-dimensional geometrical features and calculation of
      unsteady flows are becoming commonplace. Automation of CFD, coupling with thermal
      models of the solid components, and extension of CFD models to include both air
      system and main gas path flows are current areas of development. CFD is also
      being used as a research tool to investigate a number of flow phenomena that are
      not yet fully understood. These include buoyancy-affected flows in rotating
      cavities, rim seal flows and mixed air/oil flows. Large eddy simulation has shown
      considerable promise for the buoyancy-driven flows and its use for air system
      flows is expected to expand in the future.

PMID- 17519196
TI  - Turbomachinery computational fluid dynamics: asymptotes and paradigm shifts.
AB  - This paper reviews the development of computational fluid dynamics (CFD)
      specifically for turbomachinery simulations and with a particular focus on
      application to problems with complex geometry. The review is structured by
      considering this development as a series of paradigm shifts, followed by
      asymptotes. The original S1-S2 blade-blade-throughflow model is briefly
      described, followed by the development of two-dimensional then three-dimensional
      blade-blade analysis. This in turn evolved from inviscid to viscous analysis and
      then from steady to unsteady flow simulations. This development trajectory led
      over a surprisingly small number of years to an accepted approach-a 'CFD
      orthodoxy'. A very important current area of intense interest and activity in
      turbomachinery simulation is in accounting for real geometry effects, not just in
      the secondary air and turbine cooling systems but also associated with the
      primary path. The requirements here are threefold: capturing and representing
      these geometries in a computer model; making rapid design changes to these
      complex geometries; and managing the very large associated computational models
      on PC clusters. Accordingly, the challenges in the application of the current CFD
      orthodoxy to complex geometries are described in some detail. The main aim of
      this paper is to argue that the current CFD orthodoxy is on a new asymptote and
      is not in fact suited for application to complex geometries and that a paradigm
      shift must be sought. In particular, the new paradigm must be geometry centric
      and inherently parallel without serial bottlenecks. The main contribution of this
      paper is to describe such a potential paradigm shift, inspired by the animation
      industry, based on a fundamental shift in perspective from explicit to implicit
      geometry and then illustrate this with a number of applications to
      turbomachinery.

PMID- 17519197
TI  - Unstructured mesh methods for the solution of the unsteady compressible flow
      equations with moving boundary components.
AB  - A review of a procedure for the simulation of time-dependent, inviscid and
      turbulent viscous, compressible flows involving geometries that change in time is
      presented. The adopted discretization technique employs unstructured meshes and
      both explicit and implicit time-stepping schemes. A dual time-stepping procedure
      and an ALE formulation enable flows involving moving boundary components to be
      included. Techniques that have been developed to maintain the validity of the
      unstructured mesh and to allow for the capture of moving flow features are also
      reviewed. Using the in-house developed techniques, some examples are included to
      demonstrate the use of the approach for the simulation of a number of flows of
      practical industrial interest.

PMID- 17519198
TI  - Design search and optimization in aerospace engineering.
AB  - In this paper, we take a design-led perspective on the use of computational tools
      in the aerospace sector. We briefly review the current state-of-the-art in design
      search and optimization (DSO) as applied to problems from aerospace engineering,
      focusing on those problems that make heavy use of computational fluid dynamics
      (CFD). This ranges over issues of representation, optimization problem
      formulation and computational modelling. We then follow this with a multi
      objective, multi-disciplinary example of DSO applied to civil aircraft wing
      design, an area where this kind of approach is becoming essential for companies
      to maintain their competitive edge. Our example considers the structure and
      weight of a transonic civil transport wing, its aerodynamic performance at cruise
      speed and its manufacturing costs. The goals are low drag and cost while holding
      weight and structural performance at acceptable levels. The constraints and
      performance metrics are modelled by a linked series of analysis codes, the most
      expensive of which is a CFD analysis of the aerodynamics using an Euler code with
      coupled boundary layer model. Structural strength and weight are assessed using
      semi-empirical schemes based on typical airframe company practice. Costing is
      carried out using a newly developed generative approach based on a hierarchical
      decomposition of the key structural elements of a typical machined and bolted
      wing-box assembly. To carry out the DSO process in the face of multiple competing
      goals, a recently developed multi-objective probability of improvement
      formulation is invoked along with stochastic process response surface models
      (Krigs). This approach both mitigates the significant run times involved in CFD
      computation and also provides an elegant way of balancing competing goals while
      still allowing the deployment of the whole range of single objective optimizers
      commonly available to design teams.

PMID- 17519199
TI  - Computational aeroelastic modelling of airframes and turbomachinery: progress and
      challenges.
AB  - Computational analyses such as computational fluid dynamics and computational
      structural dynamics have made major advances towards maturity as engineering
      tools. Computational aeroelasticity (CAE) is the integration of these
      disciplines. As CAE matures, it also finds an increasing role in the design and
      analysis of aerospace vehicles. This paper presents a survey of the current state
      of CAE with a discussion of recent research, success and continuing challenges in
      its progressive integration into multidisciplinary aerospace design. It
      approaches CAE from the perspective of the two main areas of application:
      airframe and turbomachinery design. An overview will be presented of the
      different prediction methods used for each field of application. Differing levels
      of nonlinear modelling will be discussed with insight into accuracy versus
      complexity and computational requirements. Subjects will include current advanced
      methods (linear and nonlinear), nonlinear flow models, use of order reduction
      techniques and future trends in incorporating structural nonlinearity. Examples
      in which CAE is currently being integrated into the design of airframes and
      turbomachinery will be presented.

PMID- 17519200
TI  - Propulsive jets and their acoustics.
AB  - The complex flow physics challenges and asks questions regarding these challenges
      a wide range of jet flows found in aerospace engineering. Hence, the daunting
      task facing Reynolds-averaged Navier-Stokes (RANS) technology, for which the time
      average of the turbulent flow field is solved, is set out. Despite the clear
      potential of large eddy simulation (LES)-related methods and hybrid forms
      involving some RANS modelling, numerous current deficiencies, mostly related to
      the limitations of computational resources, are identified. It is concluded that
      currently, these limitations make LES and hybrids most useful for understanding
      flow physics and refining RANS technology. The use of LES in conjunction with a
      ray-tracing model to elucidate the physics of acoustic wave transmission in jets
      and thus improved RANS technology is described. It is argued that, as a stopgap
      measure, pure RANS simulations can be a valuable part of the design process and
      can now predict acoustics spectra and directivity diagrams with useful accuracy.
      Ultimately, hybrid RANS-LES-type methods, and then pure LES, will dominate, but
      the time-scales for this transition suggests that improvements to RANS technology
      should not be ignored.

PMID- 17519201
TI  - A deterministic model for the sublayer streaks in turbulent boundary layers for
      application to flow control.
AB  - We present a relatively simple, deterministic, theoretical model for the sublayer
      streaks in a turbulent boundary layer based on an analogy with Klebanoff modes.
      Our approach is to generate the streamwise vortices found in the buffer layer by
      means of a vorticity source in the form of a fictitious body force. It is found
      that the strongest streaks correspond to a spanwise wavelength that lies within
      the range of the experimentally observed values for the statistical mean streak
      spacing. We also present results showing the effect of streamwise pressure
      gradient, Reynolds number and wall compliance on the sublayer streaks. The
      theoretical predictions for the effects of wall compliance on the streak
      characteristics agree well with experimental data. Our proposed theoretical model
      for the quasi-periodic bursting cycle is also described, which places the streak
      modelling in context. The proposed bursting process is as follows: (i) streamwise
      vortices generate sublayer streaks and other vortical elements generate
      propagating plane waves, (ii) when the streaks reach a sufficient amplitude, they
      interact nonlinearly with the plane waves to produce oblique waves that exhibit
      transient growth, and (iii) the oblique waves interact nonlinearly with the plane
      wave to generate streamwise vortices; these in turn generate the sublayer streaks
      and so the cycle is renewed.

PMID- 17519202
TI  - Current trends in modelling research for turbulent aerodynamic flows.
AB  - The engineering tools of choice for the computation of practical engineering
      flows have begun to migrate from those based on the traditional Reynolds-averaged
      Navier-Stokes approach to methodologies capable, in theory if not in practice, of
      accurately predicting some instantaneous scales of motion in the flow. The
      migration has largely been driven by both the success of Reynolds-averaged
      methods over a wide variety of flows and the inherent limitations of the method
      itself. Practitioners, emboldened by their ability to predict a wide variety of
      statistically steady equilibrium turbulent flows, have now turned their attention
      to flow control and non-equilibrium flows, i.e. separation control. This review
      gives some current priorities in traditional Reynolds-averaged modelling research
      as well as some methodologies being applied to a new class of turbulent flow
      control problem.

PMID- 17519203
TI  - Introduction. Computational aerodynamics.
AB  - The wide range of uses of computational fluid dynamics (CFD) for aircraft design
      is discussed along with its role in dealing with the environmental impact of
      flight. Enabling technologies, such as grid generation and turbulence models, are
      also considered along with flow/turbulence control. The large eddy simulation,
      Reynolds-averaged Navier-Stokes and hybrid turbulence modelling approaches are
      contrasted. The CFD prediction of numerous jet configurations occurring in
      aerospace are discussed along with aeroelasticity for aeroengine and external
      aerodynamics, design optimization, unsteady flow modelling and aeroengine
      internal and external flows. It is concluded that there is a lack of detailed
      measurements (for both canonical and complex geometry flows) to provide
      validation and even, in some cases, basic understanding of flow physics. Not
      surprisingly, turbulence modelling is still the weak link along with, as ever, a
      pressing need for improved (in terms of robustness, speed and accuracy) solver
      technology, grid generation and geometry handling. Hence, CFD, as a truly
      predictive and creative design tool, seems a long way off. Meanwhile, extreme
      practitioner expertise is still required and the triad of computation,
      measurement and analytic solution must be judiciously used.

PMID- 17519205
TI  - Injectable tissue-engineered cartilage using a fibrin sealant.
AB  - OBJECTIVE: To investigate a commercially available fibrin sealant as a vehicle
      for developing injectable tissue-engineered cartilage. METHODS: Fibrin glue was
      mixed with autogenous chondrocytes from rabbits (n = 15). This isolate was
      injected along their nasal dorsa using 1 of 3 different fibrin glue
      concentrations. The samples were harvested at 8 weeks and compared with elastin
      and hyaline cartilage controls. RESULTS: Neocartilage was created along a linear
      injection tract on the dorsa of the nasal bones in 5 of 15 rabbits. Higher
      thrombin concentrations proved to be directly correlated with successful creation
      of injectable cartilage. Histologically, the staining patterns of both
      hematoxylin-eosin and safranin O stains were identical to that of normal
      auricular control cartilage. The presence of elastin fibers was observed
      following Verhoeff staining. No foreign body reaction was observed from the host.
      CONCLUSIONS: This study demonstrated a successful method for percutaneous
      injection of tissue-engineered cartilage as a mixture of chondrocytes suspended
      in fibrin glue. The thrombin concentration, along with the concentration of
      fibrinogen and chondrocytes, must be optimized to succeed consistently in
      cartilage growth.

PMID- 17519206
TI  - Retrospective analysis of the Farrior technique for otoplasty.
AB  - OBJECTIVE: To evaluate clinical outcomes and patient satisfaction following
      otoplasty for surgical correction of protruding or prominent ears using the
      Farrior technique. METHODS: This was a retrospective study of patients undergoing
      cosmetic otoplasty with the Farrior method at a private facial plastic surgery
      practice in Tampa, Fla. The study population comprised 75 subjects desiring
      operative correction of auricular deformities by one of the authors (E.H.F.) over
      the past 15 years. The subjects (40 male and 35 female) ranged in age from 5 to
      68 years, with a mean age of 23.9 years. Clinical follow-up ranged from 1 day to
      7 years 2 months, with a mean duration of 1 year 5 days. The Farrior otoplasty is
      a graduated technique that combines elements of cartilage sculpting, suturing,
      and conchal setback procedures, and stresses a patient-specific, anatomy-directed
      approach. This method was first introduced in the literature in 1959 by the
      senior author (R.T.F.) and is continued to the present day by his son (E.H.F.).
      Main outcome measures included satisfactory correction of auricular deformity,
      incidence of postoperative complications, and degree of patient satisfaction with
      the procedure. These outcomes were compared with that of other otoplasty
      techniques and long-term studies in the literature. RESULTS: Of the 75 patients
      who underwent otoplasty via the Farrior technique over the last 15 years,
      bilateral otoplasties were performed in 69 (92%). Of the cases, 69 (92%) were
      primary procedures, with revision otoplasties constituting 6 (8%) of the total. A
      combination of conchal cartilage reduction, cartilage scoring, and mattress
      suturing was the most frequently used maneuver (47 cases [63%]). Most cases were
      performed using local anesthesia (n = 62 [83%]), with 18 (24%) of all cases
      having adjunctive procedures at the time of the otoplasty. No major complications
      (large hematoma, tissue necrosis, gross deformity, or significant wound
      infection) were documented. A total of 40 minor complications was observed in 29
      patients, with suture extrusion and persistent auricular protrusion being the
      most common (occurring in 14 [19%] and 17 [23%] cases, respectively). Overall, 11
      patients required revision surgery (9 for protrusion, 1 for hypertrophic scar,
      and 1 for cartilaginous callus). A majority of positive responses on an anonymous
      patient survey reflects a high degree of patient satisfaction with the procedure
      and results. CONCLUSIONS: The Farrior otoplasty is a graduated technique that has
      met with clinical success over the years. It combines elements of cartilage
      shaping and suturing procedures and as such is susceptible to complications such
      as suture extrusion and auricular protrusion that are ascribed to similar
      otoplasty methods described in the literature. It allows for a directed approach
      to correct the causative anatomic defects, while maintaining a natural
      appearance. While further research and long-term analyses are encouraged, this
      technique remains a valuable component of a facial plastic surgeon's
      armamentarium.

PMID- 17519207
TI  - The healing effects of autologous platelet gel on acute human skin wounds.
AB  - OBJECTIVE: To compare the healing of full-thickness skin punch wounds treated
      with topical autologous platelet gel (APG) vs conventional therapy (antibiotic
      ointment and/or occlusive dressings) in healthy volunteers. METHODS: A
      prospective, single-blind, pilot study comprising 80 full-thickness skin punch
      wounds (4 mm diameter) was conducted on the thighs of 8 healthy volunteers. With
      each subject serving as his or her own control (5 punch sites per leg), APG was
      applied topically on one thigh, and an antibiotic ointment and/or a semiocclusive
      dressing was applied on the other thigh. Healing was monitored for spontaneous
      wound closure by clinical assessment and by digital photographs over 6 months.
      Over 35 days, 64 serial dermal biopsy specimens (6 mm diameter) were analyzed
      (using hematoxylin-eosin, Mason trichrome, CD-34, and Ki-67 stains) to measure
      differences between treated and control sites for cellularity, granulation
      formation, vascularity, epithelialization, and cellular replication. RESULTS:
      Over a 42-day period, the APG-treated sites had statistically increased wound
      closure compared with controls by visual clinical assessment and by digital
      planimetry photographic measurements (P<or=.02). On day 17, the percentage of
      closure was 81.1% +/- 2.5% (mean +/- SE) for the APG-treated sites and 57.2% +/-
      5.9% for the control sites. Also, the APG wound closure velocities were
      significantly faster than those of the controls (P = .001). Histologically, over
      time, the APG-treated sites had similar cellularity, cellular replication,
      granulation tissue, vascularity, and epithelialization compared with controls.
      However, when the platelet count in the gel was more than 6 times the baseline
      intravascular platelet count in some subjects, epithelialization and granulation
      formation appeared 3 days earlier in the APG-treated group. Furthermore, in vitro
      testing of supplemental APG showed increased endothelial cell proliferation
      compared with controls (P<.04). CONCLUSION: This pilot study provides preliminary
      evidence that topical APG may hasten wound closure in full-thickness dermal
      wounds in healthy individuals. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00199992.

PMID- 17519208
TI  - Suture biomechanics and static facial suspension.
AB  - BACKGROUND: Static facial suspension (SFS) continues to play a role for
      rehabilitation in patients with facial paralysis. We perform SFS almost
      exclusively with a suture technique in our practice. Monofilament polypropylene
      suture (Prolene) is commonly used for SFS, but we have witnessed occasional
      failure and some stretching with this material. The purpose of this study was to
      establish and compare the biomechanical properties of 3 suture types
      polypropylene, polybutilate-coated braided polyester (PBCP) (Ethibond Excel), and
      braided polyester impregnated with polytetrafluoroethylene (PIP) (Tevdek)-to
      assess their suitability for SFS. METHODS: Six samples of 0, 2-0, and 3-0
      polypropylene, PBCP, and PIP were tested. The mean load to failure was calculated
      for each suture type. Stiffness and elongation at specific loads were calculated
      to compare stretch between materials. RESULTS: The load to failure of PBCP and
      PIP was significantly greater than that for polypropylene for all suture sizes.
      In addition, PBCP and PIP had significantly less elongation than did
      polypropylene at clinically relevant loads. CONCLUSIONS: Both PBCP and PIP had
      superior load-bearing properties and decreased stretch when compared with
      polypropylene. These properties suggest that, for SFS with suture, use of PBCP or
      PIP may reduce the incidence of breakage and elongation, improving outcomes.

PMID- 17519209
TI  - Gangplank flap reconstruction of the nose.
AB  - In subtotal nose reconstruction, different tissues have to be reconstructed. We
      report the case of a 51-year-old man with a severe deformity of the nose
      (shortening and collapse of the nose, retraction of the right alar area, and a
      total septal defect after surgery and radiotherapy for a septum nasi carcinoma).
      Reconstruction with good results was performed with a "gangplank" flap technique
      (using a U-shaped skin flap for inner lining and for lengthening), rib cartilage
      for the nasal skeleton, and skin coverage with a paramedian forehead flap.

PMID- 17519204
TI  - Single-molecule biophysics: at the interface of biology, physics and chemistry.
AB  - Single-molecule methods have matured into powerful and popular tools to probe the
      complex behaviour of biological molecules, due to their unique abilities to probe
      molecular structure, dynamics and function, unhindered by the averaging inherent
      in ensemble experiments. This review presents an overview of the burgeoning field
      of single-molecule biophysics, discussing key highlights and selected examples
      from its genesis to our projections for its future. Following brief introductions
      to a few popular single-molecule fluorescence and manipulation methods, we
      discuss novel insights gained from single-molecule studies in key biological
      areas ranging from biological folding to experiments performed in vivo.

PMID- 17519210
TI  - Efficacy and safety of endotine fixation device in endoscopic brow-lift.

PMID- 17519217
TI  - Randomized double-blind trial of treatment of vitiligo: efficacy of psoralen-UV-A
      therapy vs Narrowband-UV-B therapy.
AB  - OBJECTIVE: To compare the efficacy of oral psoralen-UV-A (PUVA) with that of
      narrowband-UV-B (NB-UVB) phototherapy in patients with nonsegmental vitiligo.
      DESIGN: Double-blind randomized study. SETTING: Phototherapy unit in a university
      hospital. PATIENTS: Fifty-six patients with nonsegmental vitiligo. Interventions
      Twice-weekly therapy with PUVA or NB-UVB. MAIN OUTCOME MEASURES: The change in
      body surface area affected by vitiligo and the color match of repigmented skin
      compared with unaffected skin were assessed after 48 sessions of therapy, at the
      end of the therapy course, and 12 months after the end of therapy. RESULTS: The
      results in the 25 patients each in the PUVA and NB-UVB groups who began therapy
      were analyzed. The median number of treatments was 47 in the PUVA-treated group
      and 97 in the NB-UVB-treated group (P = .03); we suspect this difference was
      because of the differences in efficacy and adverse effects between the 2
      modalities, such that patients in the NB-UVB group wanted a longer course of
      treatment. At the end of therapy, 16 (64%) of 25 patients in the NB-UVB group
      showed greater than 50% improvement in body surface area affected compared with 9
      (36%) of 25 patients in the PUVA group. The color match of the repigmented skin
      was excellent in all patients in the NB-UVB group but in only 11 (44%) of those
      in the PUVA group (P<.001). In patients who completed 48 sessions, the
      improvement in body surface area affected by vitiligo was greater with NB-UVB
      therapy than with PUVA therapy (P = .007). Twelve months after the cessation of
      therapy, the superiority of NB-UVB tended to be maintained. CONCLUSION: In the
      treatment of nonsegmental vitiligo, NB-UVB therapy is superior to oral PUVA
      therapy.

PMID- 17519218
TI  - Bath PUVA and saltwater baths followed by UV-B phototherapy as treatments for
      psoriasis: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of psoralens dissolved in a warm-water bath
      followed by exposure to UV-A irradiation (bath PUVA) or saltwater phototherapy
      (SW UV-B) compared with tap-water phototherapy (TW UV-B) or UV-B irradiation
      alone in psoriasis. DESIGN: Multisite, prospective, randomized, controlled trial
      with 4 parallel groups. SETTING: Total of 102 dermatologic outpatient clinics.
      PATIENTS: Total of 1241 patients with stable psoriasis vulgaris and a Psoriasis
      Area and Severity Index score of 7 or greater. INTERVENTIONS: Four-times-weekly
      UV-B, TW UV-B, SW UV-B, or bath-PUVA with baths preceding UV irradiation over a
      maximum of 8 weeks. The UV dose was adapted to erythemal response. MAIN OUTCOME
      MEASURES: Incidence of therapeutic success, defined as a reduction of the
      Psoriasis Area and Severity Index or affected body surface area of 50% or more.
      RESULTS: Patients who received TW UV-B had a significantly higher incidence of
      therapeutic success than did patients treated with UV-B alone (60.7% vs 43.3%;
      P<.001; number needed to treat, 5.8; 95% confidence interval [CI], 3.9-10.9).
      Patients who received SW UV-B or bath PUVA had a significantly higher incidence
      of therapeutic success than did patients treated with TW UV-B (74.9% vs 60.7%;
      P<.001; number needed to treat, 7.0; 95% CI, 4.6-14.9; and 78.4% vs 60.7%;
      P<.001; number needed to treat, 5.7; 95% CI, 4.0-9.7, respectively). Bath PUVA
      was not superior to SW UV-B (78.4% vs 74.9%; P = .34). CONCLUSION: Bath PUVA and
      SW UV-B are comparably effective treatments in psoriasis and superior to UV-B and
      TW UV-B.

PMID- 17519219
TI  - Adult disseminated primary papular xanthoma treated with doxycycline.

PMID- 17519221
TI  - Fragile X mental retardation protein modulates the fate of germline stem cells in
      Drosophila.
AB  - Fragile X syndrome, a common form of inherited mental retardation, is caused by
      the loss of fragile X mental retardation protein (FMRP). FMRP, which may regulate
      translation in neurons, associates not only with specific mRNAs and microRNAs
      (miRNA), but also with components of the miRNA pathway, including Dicer and
      Argonaute proteins. In Drosophila, dFmr1 is also known to be involved in germ
      cell and oocyte specification; however, the question of whether dFmr1 is required
      for controlling the fate of germline stem cells (GSCs) has gone unanswered. Here
      we show that dFmr1 is required for both GSC maintenance and repressing
      differentiation. Furthermore, we demonstrate that in Drosophila ovary, dFmr1
      protein interacts with Argonaute protein 1 (AGO1), a key component of the miRNA
      pathway. Thus dFmr1 could modulate the fate of GSCs, likely via the miRNA
      pathway. Our results provide the first evidence that FMRP might be involved in
      the regulation of adult stem cells.

PMID- 17519220
TI  - Genome-wide expression profiling of lymphoblastoid cell lines distinguishes
      different forms of autism and reveals shared pathways.
AB  - Autism is a heterogeneous condition that is likely to result from the combined
      effects of multiple genetic factors interacting with environmental factors. Given
      its complexity, the study of autism associated with Mendelian single gene
      disorders or known chromosomal etiologies provides an important perspective. We
      used microarray analysis to compare the mRNA expression profile in lymphoblastoid
      cells from males with autism due to a fragile X mutation (FMR1-FM), or a 15q11
      q13 duplication (dup(15q)), and non-autistic controls. Gene expression profiles
      clearly distinguished autism from controls and separated individuals with autism
      based on their genetic etiology. We identified 68 genes that were dysregulated in
      common between autism with FMR1-FM and dup(15q). We also identified a potential
      molecular link between FMR1-FM and dup(15q), the cytoplasmic FMR1 interacting
      protein 1 (CYFIP1), which was up-regulated in dup(15q) patients. We were able to
      confirm this link in vitro by showing common regulation of two other dysregulated
      genes, JAKMIP1 and GPR155, downstream of FMR1 or CYFIP1. We also confirmed the
      reduction of the Jakmip1 protein in Fmr1 knock-out mice, demonstrating in vivo
      relevance. Finally, we showed independent confirmation of roles for JAKMIP1 and
      GPR155 in autism spectrum disorders (ASDs) by showing their differential
      expression in male sib pairs discordant for idiopathic ASD. These results provide
      evidence that blood derived lymphoblastoid cells gene expression is likely to be
      useful for identifying etiological subsets of autism and exploring its
      pathophysiology.

PMID- 17519222
TI  - Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity:
      the two facets of a Janus obesity gene.
AB  - The melanocortin-4 receptor (MC4R) gene pathogenic mutations are the most
      prevalent forms of monogenic obesity, responsible for approximately 2% of obesity
      cases, but its role in common obesity is still elusive. We analyzed the
      contribution of non-synonymous mutations V103I (rs2229616, c.307G > A) and I251L
      (no rs, c.751A > C) to obesity in 16 797 individuals of European origin from nine
      independent case-control, population-based and familial cohorts. We observed a
      consistent negative association of I251L variant (prevalence ranging 0.41-1.21%)
      with both childhood and adult class III obesity [odds ratio (OR) ranging from
      0.25 to 0.76, 0.001 < P-value < 0.05] and with modulation of body mass index
      (BMI) in general populations, in eight out of nine studies, whereas only one
      study showed an association between V103I and BMI. Meta-analyses of previous
      published data with the current ones provided strong evidence of the protective
      effect of I251L toward obesity (OR = 0.52, P = 3.58 10-5), together with a modest
      negative association between V103I and obesity (OR = 0.80, P = 0.002). Taken
      together, gain-of-function mutations I251L and V103I may be responsible for a
      preventive fraction of obesity of 2%, which mirrors the prevalence of monogenic
      obesity due to MC4R haploinsufficiency. These results also emphasize the
      importance of the MC4R signalling tonus to prevent obesity, even in the context
      of our current obesogenic environment.

PMID- 17519223
TI  - Mutant huntingtin's effects on striatal gene expression in mice recapitulate
      changes observed in human Huntington's disease brain and do not differ with
      mutant huntingtin length or wild-type huntingtin dosage.
AB  - To test the hypotheses that mutant huntingtin protein length and wild-type
      huntingtin dosage have important effects on disease-related transcriptional
      dysfunction, we compared the changes in mRNA in seven genetic mouse models of
      Huntington's disease (HD) and postmortem human HD caudate. Transgenic models
      expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice)
      exhibited the most rapid effects on gene expression, consistent with previous
      studies. Although changes in the brains of knock-in and full-length transgenic
      models of HD took longer to appear, 15- and 22-month CHL2(Q150/Q150), 18-month
      Hdh(Q92/Q92) and 2-year-old YAC128 animals also exhibited significant HD-like
      mRNA signatures. Whereas it was expected that the expression of full-length
      huntingtin transprotein might result in unique gene expression changes compared
      with those caused by the expression of an N-terminal huntingtin fragment, no
      discernable differences between full-length and fragment models were detected. In
      addition, very high correlations between the signatures of mice expressing normal
      levels of wild-type huntingtin and mice in which the wild-type protein is absent
      suggest a limited effect of the wild-type protein to change basal gene expression
      or to influence the qualitative disease-related effect of mutant huntingtin. The
      combined analysis of mouse and human HD transcriptomes provides important
      temporal and mechanistic insights into the process by which mutant huntingtin
      kills striatal neurons. In addition, the discovery that several available lines
      of HD mice faithfully recapitulate the gene expression signature of the human
      disorder provides a novel aspect of validation with respect to their use in
      preclinical therapeutic trials.

PMID- 17519224
TI  - Genetic haplotypes of Th-2 immune signalling link allergy to enhanced protection
      to parasitic worms.
AB  - Parasitic worm infection, allergy and asthma involve increased IgE production,
      eosinophil activity, mucus secretion and smooth muscle reactivity, effected
      through Th-2 immune signalling. These pathological features of allergic disorder,
      common in developed countries, appear to be protective features in resistance to
      parasitic worm infections prevalent in many developing countries. We investigated
      how genetic variation in the Th-2 signalling transduction molecule STAT6 relates
      to these clinical disorders, using immune phenotyping by serum IgE levels and
      haplotyping nine STAT6 genetic variants in a rural Chinese population, where
      Ascaris infection is prevalent, and an urban UK population where Ascaris is
      largely unknown but asthma and allergy are prevalent. We show for the first time
      that STAT6 haplotypes relate clearly to IgE levels, allergy and worm burden. The
      haplotypes segregated into two groups: those with raised IgE/low worm burden
      tended to have increased risk of allergic disorder, whereas low IgE/high worm
      burden tended to have a reduced risk of allergies. By estimating the mean worm
      burden for each haplotype in China and the relative risk of asthma for the
      matching haplotype in the UK, we draw a cross-population comparison and show a
      negative correlation between worm burden and expected risk of asthma. These data
      imply that the origin of common up-regulating variants of Th-2 signalling,
      involving STAT6, promotes asthma and allergy in developed countries, whereas in
      developing countries it protects against parasitic worm infections. Selective
      evolutionary mechanisms, driven by parasitic worm infection, may underlie the
      genetic contribution to risk of allergy and asthma in humans.

PMID- 17519225
TI  - Global survey of human T leukemic cells by integrating proteomics and
      transcriptomics profiling.
AB  - A global protein survey is needed to gain systems-level insights into mammalian
      cell signaling and information flow. Human Jurkat T leukemic cells are one of the
      most important model systems for T cell signaling study, but no comprehensive
      proteomics survey has been carried out in this cell type. In the present study we
      combined subcellular fractionation, multiple protein enrichment methods, and
      replicate tandem mass spectrometry analyses to determine the protein expression
      pattern in a single Jurkat cell type. The proteome dataset was evaluated by
      comparison with the genome-wide mRNA expression pattern in the same cell type. A
      total of 5381 proteins were identified by mass spectrometry with high confidence.
      Rigorous comparison of RNA and protein expression afforded removal of the false
      positive identifications and redundant entries but rescued the proteins
      identified by a single high scoring peptide, resulting in the final
      identification of 6471 unique gene products among which 98% of the corresponding
      transcripts were detected with high probability. Using hierarchical clustering of
      the protein expression patterns in five subcellular fractions (cytosol, light
      membrane, heavy membrane, mitochondria, and nuclei), the primary subcellular
      localization of 2241 proteins was assigned with high confidence including 792
      previously uncharacterized proteins. This proteome landscape can serve as a
      useful platform for systems-level understanding of organelle composition and
      cellular functions in human T cells.

PMID- 17519226
TI  - Gold nanoparticle assembly microfluidic reactor for efficient on-line
      proteolysis.
AB  - A microchip reactor coated with a gold nanoparticle network entrapping trypsin
      was designed for the efficient on-line proteolysis of low level proteins and
      complex extracts originating from mouse macrophages. The nanostructured surface
      coating was assembled via a layer-by-layer electrostatic binding of
      poly(diallyldimethylammonium chloride) and gold nanoparticles. The assembly
      process was monitored by UV-visible spectroscopy, atomic force microscopy, and
      quartz crystal microbalance. The controlled adsorption of trypsin was
      theoretically studied on the basis of the Langmuir isotherm model, and the fitted
      Gamma(max) and K values were estimated to be 1.2 x 10(-7) mol/m(2) and 4.1 x
      10(5) M(-1), respectively. An enzymatic kinetics assay confirmed that trypsin,
      which was entrapped in the biocompatible gold nanoparticle network with a high
      loading capacity, preserved its bioactivity. The maximum proteolytic rate of the
      adsorbed trypsin was 400 mM/(min.microg). Trace amounts of proteins down to
      femtomole per analysis were digested using the microchip reactor, and the
      resulting tryptic products were identified by MALDI-TOF MS/MS. The protein
      mixtures extracted from the mouse macrophages were efficiently identified by on
      line digestion and LC-ESI-MS/MS analysis.

PMID- 17519227
TI  - Activated platelets and monocytes generate four hydroxyphosphatidylethanolamines
      via lipoxygenase.
AB  - 12/15-Lipoxygenase (LOX) mediates immune-regulatory activities not accounted for
      by its known free acid eicosanoids, suggesting that additional lipids may be
      generated by activated cells. To characterize novel LOX-derived lipids, a
      lipidomic approach was utilized. Ionophore-activated interleukin-4-treated human
      peripheral monocytes generated up to 10-fold more esterified 15
      hydroxyeicosatetraenoic acid (15-HETE) than free in a phosphatidylinositol 3
      kinase- and protein kinase C-sensitive manner. Precursor scanning electrospray
      ionization/tandem spectroscopy for m/z 319 (HETE, [M-H](-)) showed 4 ions at m/z
      738, 764, 766, and 782 that were identified using tandem spectroscopy and MS3 as
      specific diacyl and plasmalogen 15-HETE phosphatidylethanolamines. Using H
      (18)(2)O water, the compounds were shown to form by direct oxidation of
      endogenous phosphatidylethanolamine (PE) by 15-LOX, with PE being the preferred
      phospholipid pool containing 15-HETE. Similarly, human platelets generated 4
      analogous PE lipids that contained 12-HETE and increased significantly in
      response to ionophore, collagen, or convulxin. These products were retained in
      the cells, in contrast to free acids, which are primarily secreted. Precursor
      scanning of platelet extracts for the major platelet-derived prostanoid,
      thromboxane B2 (m/z 369.2), did not reveal PE esters, indicating that this
      modification is restricted to the LOX pathway. In summary, we show formation of
      PE-esterified HETEs in immune cells that may contribute to LOX signaling in
      inflammation.

PMID- 17519228
TI  - Biochemical characterization of the polysialic acid-specific O-acetyltransferase
      NeuO of Escherichia coli K1.
AB  - Escherichia coli K1 is a leading pathogen in neonatal sepsis and meningitis. The
      K1 capsule, composed of alpha2,8-linked polysialic acid, represents the major
      virulence factor. In some K1 strains, phase-variable O-acetylation of the
      capsular polysaccharide is observed, a modification that is catalyzed by the
      prophage-encoded O-acetyltransferase NeuO. Phase variation is mediated by changes
      in the number of heptanucleotide repeats within the 5'-coding region of neuO, and
      full-length translation is restricted to repeat numbers that are a multiple of
      three. To understand the biochemical basis of K1 capsule O-acetylation, NeuO
      encoded by alleles containing 0, 12, 24, and 36 repeats was expressed and
      purified to homogeneity via a C-terminal hexahistidine tag. All NeuO variants
      assembled into hexamers and were enzymatically active with a high substrate
      specificity toward polysialic acid with >14 residues. Remarkably, the catalytic
      efficiency (k(cat)/K(m)(donor)) increased linearly with increasing numbers of
      repeats, revealing a new mechanism for modulating NeuO activity. Using homology
      modeling, we predicted a three-dimensional structure primarily composed of a left
      handed parallel beta-helix with one protruding loop. Two amino acids critical for
      catalytic activity were identified and corresponding alanine substitutions, H119A
      and W143A, resulted in a complete loss of activity without affecting the
      oligomerization state. Our results indicate that in NeuO typical features of an
      acetyltransferase of the left-handed beta-helix family are combined with a unique
      regulatory mechanism based on variable N-terminal protein extensions formed by
      tandem copies of an RLKTQDS heptad.

PMID- 17519229
TI  - Replacement of nonmuscle myosin II-B with II-A rescues brain but not cardiac
      defects in mice.
AB  - The purpose of these studies was to learn whether one isoform of nonmuscle myosin
      II, specifically nonmuscle myosin II-A, could functionally replace a second one,
      nonmuscle myosin II-B, in mice. To accomplish this, we used homologous
      recombination to ablate nonmuscle myosin heavy chain (NMHC) II-B by inserting
      cDNA encoding green fluorescent protein (GFP)-NMHC II-A into the first coding
      exon of the Myh10 gene, thereby placing GFP-NMHC II-A under control of the
      endogenous II-B promoter. Similar to B(-)/B(-) mice, most B(a*)/B(a*) mice died
      late in embryonic development with structural cardiac defects and impaired
      cytokinesis of the cardiac myocytes. However, unlike B(-)/B(-) mice, 15
      B(a*)/B(a*) mice of 172 F2 generation mice survived embryonic lethality but
      developed a dilated cardiomyopathy as adults. Surprisingly none of the
      B(a*)/B(a*) mice showed evidence for hydrocephalus that is always found in B(
      )/B(-) mice. Rescue of this defect was due to proper localization and function of
      GFP-NMHC II-A in place of NMHC II-B in a cell-cell adhesion complex in the cells
      lining the spinal canal. Restoration of the integrity and adhesion of these cells
      prevents protrusion of the underlying cells into the spinal canal where they
      block circulation of the cerebral spinal fluid. However, abnormal migration of
      facial and pontine neurons found in NMHC II-B mutant and ablated mice persisted
      in B(a*)/B(a*) mice. Thus, although NMHC II-A can substitute for NMHC II-B to
      maintain integrity of the spinal canal, NMHC II-B plays an isoform-specific role
      during cytokinesis in cardiac myocytes and in migration of the facial and pontine
      neurons.

PMID- 17519230
TI  - Agonist-modulated regulation of AMP-activated protein kinase (AMPK) in
      endothelial cells. Evidence for an AMPK -> Rac1 -> Akt -> endothelial nitric
      oxide synthase pathway.
AB  - The endothelial isoform of nitric-oxide synthase (eNOS), a key determinant of
      vascular homeostasis, is a calcium/calmodulin-dependent phosphoprotein regulated
      by diverse cell surface receptors. Vascular endothelial growth factor (VEGF) and
      sphingosine 1-phosphate (S1P) stimulate eNOS activity through
      Akt/phosphoinositide 3-kinase and calcium-dependent pathways. AMP-activated
      protein kinase (AMPK) also activates eNOS in endothelial cells; however, the
      molecular mechanisms linking agonist-mediated AMPK regulation with eNOS
      activation remain incompletely understood. We studied the role of AMPK in VEGF-
      and S1P-mediated eNOS activation and found that both agonists led to a striking
      increase in AMPK phosphorylation in pathways involving the calcium/calmodulin
      dependent protein kinase kinase beta. Treatment with tyrosine kinase inhibitors
      or the phosphoinositide 3-kinase inhibitor wortmannin demonstrated differential
      effects of VEGF versus S1P. Small interfering RNA (siRNA)-mediated knockdown of
      AMPKalpha1or Akt1 impaired the stimulatory effects of both VEGF and S1P on eNOS
      activation. AMPKalpha1 knockdown impaired agonist-mediated Akt phosphorylation,
      whereas Akt1 knockdown did not affect AMPK activation, thus suggesting that AMPK
      lies upstream of Akt in the pathway leading from receptor activation to eNOS
      stimulation. Importantly, we found that siRNA-mediated knockdown of AMPKalpha1
      abrogates agonist-mediated activation of the small GTPase Rac1. Conversely, siRNA
      mediated knockdown of Rac1 decreased the agonist-mediated phosphorylation of AMPK
      substrates without affecting that of AMPK, implicating Rac1 as a molecular link
      between AMPK and Akt in agonist-mediated eNOS activation. Finally, siRNA-mediated
      knockdown of caveolin-1 significantly enhanced AMPK phosphorylation, suggesting
      that AMPK is negatively regulated by caveolin-1. Taken together, these results
      suggest that VEGF and S1P differentially regulate AMPK and establish a central
      role for an agonist-modulated AMPK --> Rac1 --> Akt axis in the control of eNOS
      in endothelial cells.

PMID- 17519231
TI  - Species-specific differences in the intermediate states of human and Syrian
      hamster prion protein detected by high pressure NMR spectroscopy.
AB  - Human (huPrP) and Syrian hamster (ShaPrP) prion proteins have barriers for mutual
      infectivity, although they fold into almost an identical structure. The pressure
      responses of huPrP and ShaPrP characterized by high pressure NMR spectroscopy
      show differences in their excited states, as monitored by pressure-induced
      chemical shifts and intensity changes of individual residues in the (15)N/(1)H
      HSQC spectra. Both proteins fluctuate rapidly between two well folded (native)
      conformations N(1) and N(2) and less frequently between N and the excited states
      I(1) and I(2) with local disorder that may present structural intermediates on
      the way to PrP(Sc). These four structural states can be observed in the hamster
      and human PrP. At ambient pressure, less than 5 molecules of 10,000 are in the
      intermediate state I(2). From the structural point of view, the different states
      are mutually different, particularly in positions strategically important for
      generating species barriers for infection. The results point to the notion that
      excited state conformers are important for infection and that their structural
      differences may crucially determine species barriers for infection.

PMID- 17519232
TI  - The localization and activity of sphingosine kinase 1 are coordinately regulated
      with actin cytoskeletal dynamics in macrophages.
AB  - The physiologic and pathologic functions of sphingosine kinase (SK) require
      translocation to specific membrane compartments. We tested the hypothesis that
      interactions with actin filaments regulate the localization of SK1 to membrane
      surfaces, including the plasma membrane and phagosome. Macrophage activation is
      accompanied by a marked increase in association of SK1 with actin filaments.
      Catalytically-inactive (CI)- and phosphorylation-defective (PD)-SK1 mutants
      exhibited reductions in plasma membrane translocation, colocalization with
      cortical actin filaments, membrane ruffling, and lamellipodia formation, compared
      with wild-type (WT)-SK1. However, translocation of CI- and PD-SK1 to phagosomes
      were equivalent to WT-SK1. SK1 exhibited constitutive- and stimulus-enhanced
      association with actin filaments and F-actin-enriched membrane fractions in both
      intact macrophages and a novel in vitro assay. In contrast, SK1 bound G-actin
      only under stimulated conditions. Actin inhibitors disrupted SK1 localization and
      modulated its activity. Conversely, reduction of SK1 levels or activity via RNA
      interference or specific chemical inhibition resulted in dysregulation of actin
      filaments. Thus, the localization and activity of SK1 are coordinately regulated
      with actin dynamics during macrophage activation.

PMID- 17519233
TI  - Nitric oxide down-regulates caveolin-3 levels through the interaction with
      myogenin, its transcription factor.
AB  - Certain patients suffering from chronic diseases such as AIDS or cancer
      experience a constant cellular secretion of tumor necrosis factor alpha and other
      pro-inflammatory cytokines that results in a continuous release of nitric oxide
      (*NO) to the bloodstream. One immediate consequence of the deleterious action of
      *NO is weight loss and the progressive destruction of muscular mass in a process
      known as cachexia. We have previously reported that caveolin-3, a specific marker
      of muscle cells, becomes down-regulated by the action of *NO on muscular
      myotubes. We describe herein that the changes observed in caveolin-3 levels are
      due to the alteration of the DNA binding activity of the muscular transcription
      factor myogenin. In the presence of *NO, the binding of transcription factors
      from cell nuclear extracts of muscular tissues to the E boxes present in the
      caveolin-3 promoter become substantially reduced. When we purified recombinant
      myogenin and treated it with *NO donors, we could detect its S-nitrosylation by
      three independent methods, suggesting that very likely one of the cysteine
      residues of the molecule is being modified. Given the role of myogenin as a
      regulatory protein that determines the level of multiple muscle genes expressed
      during late myogenesis, our results might represent a novel mode of regulation of
      muscle development under conditions of nitric oxide-mediated toxicity.

PMID- 17519234
TI  - Human peroxiredoxin 1 and 2 are not duplicate proteins: the unique presence of
      CYS83 in Prx1 underscores the structural and functional differences between Prx1
      and Prx2.
AB  - Human peroxiredoxins 1 and 2, also known as Prx1 and Prx2, are more than 90%
      homologous in their amino acid sequences. Prx1 and Prx2 are elevated in various
      cancers and are shown to influence diverse cellular processes. Although their
      growth regulatory role has traditionally been attributed to the peroxidase
      activity, the physiological significance of this function is unclear because the
      proteins are highly susceptible to inactivation by H(2)O(2). A chaperone activity
      appears to emerge when their peroxidase activity is lost. Structural studies
      suggest that they may form a homodimer or doughnut-shaped homodecamer. However,
      little information is available whether human Prx1 and Prx2 are duplicative in
      structure and function. We noted that Prx1 contains a cysteine (Cys(83)) at the
      putative dimer-dimer interface, which is absent in Prx2. We studied the role of
      Cys(83) in regulating the peroxidase and chaperone activities of Prx1, because
      the redox status of Cys(83) might influence the oligomeric structure and
      consequently the functions of Prx1. We show that Prx1 is more efficient as a
      molecular chaperone, whereas Prx2 is better suited as a peroxidase enzyme.
      Substituting Cys(83) with Ser(83) (Prx1C83S) results in dramatic changes in the
      structural and functional characteristics of Prx1 in a direction similar to those
      of Prx2. Here we also report the first crystal structure of human Prx1 and the
      presence of the Cys(83)-Cys(83) bond at the dimer-dimer interface of decameric
      Prx1. These findings are consistent with the hypothesis that human Prx1 and Prx2
      possess unique functions and regulatory mechanisms and that Cys(83) bestows a
      distinctive identity to Prx1.

PMID- 17519235
TI  - Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived
      versus eicosapentaenoic acid-derived substrates and products.
AB  - Dietary fish oil containing omega 3 highly unsaturated fatty acids has
      cardioprotective and anti-inflammatory effects. Prostaglandins (PGs) and
      thromboxanes are produced in vivo both from the omega 6 fatty acid arachidonic
      acid (AA) and the omega 3 fatty acid eicosapentaenoic acid (EPA). Certain
      beneficial effects of fish oil may result from altered PG metabolism resulting
      from increases in the EPA/AA ratios of precursor phospholipids. Here we report in
      vitro specificities of prostanoid enzymes and receptors toward EPA-derived, 3
      series versus AA-derived, 2-series prostanoid substrates and products. The
      largest difference was seen with PG endoperoxide H synthase (PGHS)-1. Under
      optimal conditions purified PGHS-1 oxygenates EPA with only 10% of the efficiency
      of AA, and EPA significantly inhibits AA oxygenation by PGHS-1. Two- to 3-fold
      higher activities or potencies with 2-series versus 3-series compounds were
      observed with PGHS-2, PGD synthases, microsomal PGE synthase-1 and EP1, EP2, EP3,
      and FP receptors. Our most surprising observation was that AA oxygenation by PGHS
      2 is only modestly inhibited by EPA (i.e. PGHS-2 exhibits a marked preference for
      AA when EPA and AA are tested together). Also unexpectedly, TxA(3) is about
      equipotent to TxA(2) at the TP alpha receptor. Our biochemical data predict that
      increasing phospholipid EPA/AA ratios in cells would dampen prostanoid signaling
      with the largest effects being on PGHS-1 pathways involving PGD, PGE, and PGF.
      Production of 2-series prostanoids from AA by PGHS-2 would be expected to
      decrease in proportion to the compensatory decrease in the AA content of
      phospholipids that would result from increased incorporation of omega 3 fatty
      acids such as EPA.

PMID- 17519236
TI  - Promotion of cancer cell migration: an insulin-like growth factor (IGF)
      independent action of IGF-binding protein-6.
AB  - A family of six high affinity IGF-binding proteins (IGFBPs 1-6) plays an
      important role in modulating IGF activities. Recent studies suggest that some
      IGFBPs may have IGF-independent effects, including induction of apoptosis and
      modulation of cell migration. However, very little is known about possible IGF
      independent actions of IGFBP-6. We have generated a non-IGF-binding IGFBP-6
      mutant by substituting Ala for four amino acid residues
      (Pro(93)/Leu(94)/Leu(97)/Leu(98)) in its N-domain IGF-binding site. A >10,000
      fold loss of binding affinity for IGF-I and IGF-II was observed using charcoal
      solution binding assay, BIAcore biosensor, and ligand blotting. Wild-type and
      mutant IGFBP-6, as well as IGF-II, induced cell migration in RD rhabdomyosarcoma
      and LIM 1215 colon cancer cells. Cell migration was mediated by the C-domain of
      IGFBP-6. Transient p38 phosphorylation was observed in RD cells after treatment
      with IGFBP-6, whereas no change was seen in phospho-ERK1/2 levels. Phospho-JNK
      was not detected. IGFBP-6-induced cell migration was inhibited by SB203580, an
      inhibitor of p38 MAPK, and PD98059, an inhibitor of ERK1/2 MAPK activation. In
      contrast, SP600125, a JNK MAPK inhibitor, had no effect on migration. Knockdown
      of p38 MAPK using short interfering RNA blocked IGFBP-6-induced migration of RD
      cells. These results indicate that p38 MAPK is involved in IGFBP-6-induced IGF
      independent RD cell migration.

PMID- 17519237
TI  - The putative moss 3'-phosphoadenosine-5'-phosphosulfate reductase is a novel form
      of adenosine-5'-phosphosulfate reductase without an iron-sulfur cluster.
AB  - Sulfate assimilation provides reduced sulfur for synthesis of the amino acids
      cysteine and methionine and for a range of other metabolites. Sulfate has to be
      activated prior to reduction by adenylation to adenosine 5'-phosphosulfate (APS).
      In plants, algae, and many bacteria, this compound is reduced to sulfite by APS
      reductase (APR); in fungi and some cyanobacteria and gamma-proteobacteria, a
      second activation step, phosphorylation to 3'-phosphoadenosine 5'-phosphosulfate
      (PAPS), is necessary before reduction to sulfite by PAPS reductase (PAPR). We
      found previously that the moss Physcomitrella patens is unique among these
      organisms in possessing orthologs of both APR and PAPR genes (Koprivova, A.,
      Meyer, A. J., Schween, G., Herschbach, C., Reski, R., and Kopriva, S. (2002) J.
      Biol. Chem. 277, 32195-32201). To assess the function of the two enzymes, we
      compared their biochemical properties by analysis of purified recombinant
      proteins. APR from Physcomitrella is very similar to the well characterized APRs
      from seed plants. On the other hand, we found that the putative PAPR
      preferentially reduces APS. Sequence analysis, analysis of UV-visible spectra,
      and determination of iron revealed that this new APR, named PpAPR-B, does not
      contain the FeS cluster, which was previously believed to determine the substrate
      specificity of the otherwise relatively similar enzymes. The lack of the FeS
      cluster in PpAPR-B catalysis is connected with a lower turnover rate but higher
      stability of the protein. These findings show that APS reduction without the FeS
      cluster is possible and that plant sulfate assimilation is predominantly
      dependent on reduction of APS.

PMID- 17519238
TI  - Role of a carboxylesterase in herbicide bioactivation in Arabidopsis thaliana.
AB  - Arabidopsis thaliana contains multiple carboxyesterases (AtCXEs) with activities
      toward xenobiotics, including herbicide esters that are activated to their
      phytotoxic acids upon hydrolysis. On the basis of their susceptibility to
      inhibition by organophosphates, these AtCXEs are all serine hydrolases. Using a
      trifunctional probe bearing a fluorophosphonate together with biotin and
      rhodamine to facilitate detection and recovery, four dominant serine hydrolases
      were identified in the proteome of Arabidopsis. Using a combination of protein
      purification, capture with the trifunctional probe and proteomics, one of these
      hydrolases, AtCXE12, was shown to be the major carboxyesterase responsible for
      hydrolyzing the pro-herbicide methyl-2,4-dichlorophenoxyacetate (2,4-D-methyl) to
      the phytotoxic acid 2,4-dichlorophenoxyacetic acid. Recombinant expression of the
      other identified hydrolases showed that AtCXE12 was unique in hydrolyzing 2,4-D
      methyl. To determine the importance of AtCXE12 in herbicide metabolism and
      efficacy, the respective tDNA knock-out (atcxe12) plants were characterized and
      shown to lack expression of AtCXE12 and have greatly reduced levels of 2,4-D
      methyl-hydrolyzing activity. Young atcxe12 seedlings were less sensitive than
      wild type plants to 2,4-D-methyl, confirming a role for the enzyme in herbicide
      bioactivation in Arabidopsis.

PMID- 17519239
TI  - Residues surrounding Arg336 and Arg562 contribute to the disparate rates of
      proteolysis of factor VIIIa catalyzed by activated protein C.
AB  - Activated Protein C (APC) inactivates factor VIIIa by cleavage at Arg(336) and
      Arg(562) within the A1 and A2 subunits, respectively, with reaction at the former
      site occurring at a rate approximately 25-fold faster than the latter.
      Recombinant factor VIII variants possessing mutations within the P4-P3' sequences
      were used to determine the contributions of these residues to the disparate
      cleavage rates at the two P1 sites. Specific activity values for 336(P4-P3')562,
      336(P4-P2)562, and 336(P1'-P3')562 mutants, where indicated residues surrounding
      the Arg(336) site were replaced with those surrounding Arg(562), were similar to
      wild type (WT) factor VIII; whereas 562(P4-P3')336 and 562(P4-P2)336 mutants
      showed specific activity values <1% the WT value. Inactivation rates for the 336
      site mutants were reduced approximately 6-11-fold compared with WT factor VIIIa,
      and approached values attributed to cleavage at Arg(562). Cleavage rates at
      Arg(336) were reduced approximately 100-fold for 336(P4-P3')562, and
      approximately 9-16-fold for 336(P4-P2)562 and 336(P1'-P3')562 mutants. Inhibition
      kinetics revealed similar affinities of APC for WT factor VIIIa and 336(P4
      P3')562 variant. Alternatively, the 562(P4-P3')336 variant showed a modest
      increase in cleavage rate ( approximately 4-fold) at Arg(562) compared with WT,
      whereas these rates were increased by approximately 27- and 6-fold for 562(P4
      P3')336 and 562(P4-P2)336, respectively, using the factor VIII procofactor form
      as substrate. Thus the P4-P3' residues surrounding Arg(336) and Arg(562) make
      significant contributions to proteolysis rates at each site, apparently
      independent of binding affinity. Efficient cleavage at Arg(336) by APC is
      attributed to favorable P4-P3' residues at this site, whereas cleavage at
      Arg(562) can be accelerated following replacement with more optimal P4-P3'
      residues.

PMID- 17519240
TI  - Speech intelligibility, loneliness, and sense of coherence among deaf and hard-of
      hearing children in individual inclusion and group inclusion.
AB  - This study examined the sense of coherence and loneliness of 19 children aged 12
      14 years with severe to profound hearing loss. These feelings and their
      interrelations with speech intelligibility (SI) were examined in 2 settings: in
      special classes within regular schools (group inclusion) or individuals
      integrated into regular classes (individual inclusion). Two self-report measures
      (Loneliness Questionnaire and Sense of Coherence Scale) and one SI measure were
      utilized. Results indicated no significant differences between sense of coherence
      and loneliness scores of children in the 2 settings. Children in group inclusion
      received a significantly lower average SI score than did children who were in
      individual inclusion. Examination of the relations between SI and loneliness and
      coherence in each educational setting revealed no significant relations among
      these measures for the children in the group inclusion, whereas significant
      correlations did emerge for the children who were in individual inclusion. The
      study emphasized the importance of good SI not only for basic communication but
      also as a factor that affects the child's social and emotional feelings. In
      selecting a school setting, it is important to look beyond academic factors and
      not to ignore the significant effect of SI on the child's well being in school.

PMID- 17519241
TI  - Energy and direction distribution of neutrons in workplace fields: implication of
      the results from the EVIDOS project for the set-up of simulated workplace fields.
AB  - Workplace neutron spectra from nuclear facilities obtained within the European
      project EVIDOS are compared with those of the simulated workplace fields CANEL
      and SIGMA and fields set-up with radionuclide sources at the PTB. Contributions
      of neutrons to ambient dose equivalent and personal dose equivalent are given in
      three energy intervals (for thermal, intermediate and fast neutrons) together
      with the corresponding direction distribution, characterised by three different
      types of distributions (isotropic, weakly directed and directed). The comparison
      shows that none of the simulated workplace fields investigated here can model all
      the characteristics of the fields observed at power reactors.

PMID- 17519242
TI  - Measurement of the fluence response of the GSI neutron ball in high-energy
      neutron fields produced by 500 AMeV and 800 AMeV deuterons.
AB  - Experiments were performed in Cave C of GSI (Gesellschaft fur
      Schwerionenforschung) using the LAND (Large Area Neutron Detector) in combination
      with the deflection magnet ALADIN (A LArge DIpol magNet) in front of the LAND
      where charged particles and neutrons can be separated. This arrangement is used
      to create high-energetic neutron fields by irradiation of a thick lead target (5
      cm) with deuteron beams with the energies of 500 or 800 MeV per nucleon. In break
      up reactions the neutron is separated from the proton which is deflected in the
      magnetic field of the ALADIN. The produced neutron radiation, which has a
      pronounced peak at the nucleon energy, is used to measure the fluence response of
      the GSI neutron ball. A thermoluminescence (TL) based spherical neutron dosemeter
      was developed for the area monitoring for the quantity H(10) at high-energy
      accelerators. In the same experiment, the spectral neutron fluence Phi(E) is
      measured with the LAND in the energy range from 100 MeV to 1 GeV. The measured
      fluence responses are compared with results of FLUKA calculations and the
      corresponding fluence-to-dose conversion coefficients. The measured dosemeter
      responses are too high in comparison to the calculated ones (up to approximately
      50%), the dosemeter reading gives dose values which are too high by a factor of
      1.1-2.2 related to the corresponding fluence-to-dose conversion factors.

PMID- 17519243
TI  - Investigation of properties of the TIARA neutron beam facility of importance for
      calibration applications.
AB  - Evaluation of the properties for quasi-monoenergetic neutron calibration fields
      of high energies more than 20 MeV at TIARA is proceeding for development of the
      field. Among the properties needed for the development as the standard
      calibration field, we report on measurement of the neutron beam profile using an
      imaging plate with a polyethylene converter and on estimation of the contribution
      of scattered neutrons into the irradiation field based on pulse height
      distribution at various off-beam positions measured using an organic liquid
      scintillation detector.

PMID- 17519244
TI  - Electronic personal neutron dosemeters for high energies: measurements, new
      developments and further needs.
AB  - The results of measurements with neutron energies up to 60 MeV are shown for the
      personal neutron dosemeters Thermo Electron EPD-N2, ALOKA PDM-313 and the PTB
      prototype dosemeter DOS-2002. All dosemeters show dose equivalent responses that
      are about a factor of 10, too high at 60 MeV. A new prototype dosemeter-called
      DOS-2005-consisting of a detector with a thin effective layer of 6 microm has
      been set up at PTB. The dose equivalent response of this dosemeter and that of
      the newly developed dosemeter SAPHYDOSE-N was measured up to 19 MeV. Both
      dosemeters indicate a more flat response at high neutron energies. Further needs
      optimisations, measurements and calculations-for use at high-energy accelerators
      and in space are discussed.

PMID- 17519245
TI  - Sensitivity study of CR39 track detector in an extended range Bonner sphere
      spectrometer.
AB  - Bonner sphere spectrometers (BSS) are being used widely in neutron spectrometry
      since 1960. The response to neutrons of these moderating detectors spans over a
      broad energy range. This work discusses the measurement of the sensitivity of an
      extended range BSS hosting a CR39 nuclear track detector coupled to a boron
      converter. Two kinds of boron converters were tested, the first made by natural
      boron and a second one enriched in (10)B. The BSS response functions were
      calculated with Monte Carlo simulation using the MCNPX 2.4.0. and the FLUKA
      codes.

PMID- 17519246
TI  - Predicting functionally important residues from sequence conservation.
AB  - MOTIVATION: All residues in a protein are not equally important. Some are
      essential for the proper structure and function of the protein, whereas others
      can be readily replaced. Conservation analysis is one of the most widely used
      methods for predicting these functionally important residues in protein
      sequences. RESULTS: We introduce an information-theoretic approach for estimating
      sequence conservation based on Jensen-Shannon divergence. We also develop a
      general heuristic that considers the estimated conservation of sequentially
      neighboring sites. In large-scale testing, we demonstrate that our combined
      approach outperforms previous conservation-based measures in identifying
      functionally important residues; in particular, it is significantly better than
      the commonly used Shannon entropy measure. We find that considering conservation
      at sequential neighbors improves the performance of all methods tested. Our
      analysis also reveals that many existing methods that attempt to incorporate the
      relationships between amino acids do not lead to better identification of
      functionally important sites. Finally, we find that while conservation is highly
      predictive in identifying catalytic sites and residues near bound ligands, it is
      much less effective in identifying residues in protein-protein interfaces.
      AVAILABILITY: Data sets and code for all conservation measures evaluated are
      available at http://compbio.cs.princeton.edu/conservation/

PMID- 17519247
TI  - The evolutionary forest algorithm.
AB  - MOTIVATION: Gene genealogies offer a powerful context for inferences about the
      evolutionary process based on presently segregating DNA variation. In many cases,
      it is the distribution of population parameters, marginalized over the
      effectively infinite-dimensional tree space, that is of interest. Our
      evolutionary forest (EF) algorithm uses Monte Carlo methods to generate posterior
      distributions of population parameters. A novel feature is the updating of
      parameter values based on a probability measure defined on an ensemble of
      histories (a forest of genealogies), rather than a single tree. RESULTS: The EF
      algorithm generates samples from the correct marginal distribution of population
      parameters. Applied to actual data from closely related fruit fly species, it
      rapidly converged to posterior distributions that closely approximated the exact
      posteriors generated through massive computational effort. Applied to simulated
      data, it generated credible intervals that covered the actual parameter values in
      accordance with the nominal probabilities. AVAILABILITY: A C++ implementation of
      this method is freely accessible at http://www.isds.duke.edu/~scl13

PMID- 17519248
TI  - Assortative mixing in Protein Contact Networks and protein folding kinetics.
AB  - MOTIVATION: Starting from linear chains of amino acids, the spontaneous folding
      of proteins into their elaborate 3D structures is one of the remarkable examples
      of biological self-organization. We investigated native state structures of 30
      single-domain, two-state proteins, from complex networks perspective, to
      understand the role of topological parameters in proteins' folding kinetics, at
      two length scales--as 'Protein Contact Networks (PCNs)' and their corresponding
      'Long-range Interaction Networks (LINs)' constructed by ignoring the short-range
      interactions. RESULTS: Our results show that, both PCNs and LINs exhibit the
      exceptional topological property of 'assortative mixing' that is absent in all
      other biological and technological networks studied so far. We show that the
      degree distribution of these contact networks is partly responsible for the
      observed assortativity. The coefficient of assortativity also shows a positive
      correlation with the rate of protein folding at both short- and long-contact
      scale, whereas, the clustering coefficients of only the LINs exhibit a negative
      correlation. The results indicate that the general topological parameters of
      these naturally evolved protein networks can effectively represent the structural
      and functional properties required for fast information transfer among the
      residues facilitating biochemical/kinetic functions, such as, allostery,
      stability and the rate of folding. SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 17519249
TI  - Recombination-filtered genomic datasets by information maximization.
AB  - With the increasing amount of DNA sequence data available from natural
      populations, new computational methods are needed to efficiently process raw
      sequences into formats that are applicable to a variety of analytical methods.
      One highly successful approach to inferring aspects of demographic history is
      grounded in coalescent theory. Many of these methods restrict themselves to
      perfectly tree-like genealogies (i.e. regions with no observed recombination),
      because theoretical difficulties prevent ready statistical evaluation of
      recombining regions. However, determining which recombination-filtered dataset to
      analyze from a larger recombination-rich genomic region is a non-trivial problem.
      Current applications primarily aim to quantify recombination rates (rather than
      produce optimal recombination-filtered blocks), require significant manual
      intervention, and are impractical for multiple genomic datasets in high
      throughput, automated research environments. Here, we present a fast, simple and
      automatable command-line program that extracts optimal recombination-filtered
      blocks (no four-gamete violations) from recombination-rich genomic re-sequence
      data. AVAILABILITY: http://hammerlab.biosci.arizona.edu/software.html.

PMID- 17519251
TI  - Genetic linkages between circadian clock-associated components and phytochrome
      dependent red light signal transduction in Arabidopsis thaliana.
AB  - The current best candidates for Arabidopsis thaliana clock components are CCA1
      (CIRCADIAN CLOCK-ASSOCIATED 1) and its homolog LHY (LATE ELONGATED HYPOCOTYL). In
      addition, five members of a small family, PSEUDO-RESPONSE REGULATORS (including
      PRR1, PRR3, PRR5, PRR7 and PRR9), are believed to be another type of clock
      component. The originally described member of PRRs is TOC1 (or PRR1) (TIMING OF
      CAB EXPRESSION 1). Interestingly, seedlings of A. thaliana carrying a certain
      lesion (i.e. loss-of-function or misexpression) of a given clock-associated gene
      commonly display a characteristic phenotype of light response during early
      photomorphogenesis. For instance, cca1 lhy double mutant seedlings show a shorter
      hypocotyl length than the wild type under a given fluence rate of red light (i.e.
      hypersensitivity to red light). In contrast, both toc1 single and prr7 prr5
      double mutant seedlings with longer hypocotyls are hyposensitive under the same
      conditions. These phenotypes are indicative of linkage between the circadian
      clock and red light signal transduction mechanisms. Here this issue was addressed
      by conducting combinatorial genetic and epistasis analyses with a large number of
      mutants and transgenic lines carrying lesions in clock-associated genes,
      including a cca1 lhy toc1 triple mutant and a cca1 lhy prr7 prr5 quadruple
      mutant. Taking these results together, we propose a genetic model for clock
      associated red light signaling, in which CCA1 and LHY function upstream of TOC1
      (PRR1) in a negative manner, in turn, TOC1 (PRR1) serves as a positive regulator.
      PRR7 and PRR5 also act as positive regulators, but independently from TOC1
      (PRR1). It is further suggested that these signaling pathways are coordinately
      integrated into the phytochrome-mediated red light signal transduction pathway,
      in which PIF3 (PHYTOCHROME-INTERACTING FACTOR 3) functions as a negative
      regulator immediately downstream of phyB.

PMID- 17519250
TI  - Discovering gene expression patterns in time course microarray experiments by
      ANOVA-SCA.
AB  - MOTIVATION: Designed microarray experiments are used to investigate the effects
      that controlled experimental factors have on gene expression and learn about the
      transcriptional responses associated with external variables. In these datasets,
      signals of interest coexist with varying sources of unwanted noise in a framework
      of (co)relation among the measured variables and with the different levels of the
      studied factors. Discovering experimentally relevant transcriptional changes
      require methodologies that take all these elements into account. RESULTS: In this
      work, we develop the application of the Analysis of variance-simultaneous
      component analysis (ANOVA-SCA) Smilde et al. Bioinformatics, (2005) to the
      analysis of multiple series time course microarray data as an example of
      multifactorial gene expression profiling experiments. We denoted this
      implementation as ASCA-genes. We show how the combination of ANOVA-modeling and a
      dimension reduction technique is effective in extracting targeted signals from
      data by-passing structural noise. The methodology is valuable for identifying
      main and secondary responses associated with the experimental factors and
      spotting relevant experimental conditions. We additionally propose a novel
      approach for gene selection in the context of the relation of individual
      transcriptional patterns to global gene expression signals. We demonstrate the
      methodology on both real and synthetic datasets. AVAILABILITY: ASCA-genes has
      been implemented in the statistical language R and is available at
      http://www.ivia.es/centrodegenomica/bioinformatics.htm. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 17519252
TI  - Next steps for Tennessee: a conversation with Gov. Phil Bredesen. Interview by
      Alan Weil.
AB  - In this conversation, conducted during the February 2007 meeting of the National
      Governors Association, Gov. Phil Bredesen of Tennessee discusses his views on
      health care, health information technology, and the challenges of changing a
      massive system with many moving parts. He talks about his involvement in the
      State Alliance for E-Health, which is working on privacy, licensure, and data
      communications across state lines. He discusses the state's TennCare program; his
      views on effective managed care; and his Cover Tennessee program, which seeks to
      provide low-income workers with an innovative low-cost insurance product focused
      on preventive care.

PMID- 17519253
TI  - Aprataxin, causative gene product for EAOH/AOA1, repairs DNA single-strand breaks
      with damaged 3'-phosphate and 3'-phosphoglycolate ends.
AB  - Aprataxin is the causative gene product for early-onset ataxia with ocular motor
      apraxia and hypoalbuminemia/ataxia with oculomotor apraxia type 1 (EAOH/AOA1),
      the clinical symptoms of which are predominantly neurological. Although aprataxin
      has been suggested to be related to DNA single-strand break repair (SSBR), the
      physiological function of aprataxin remains to be elucidated. DNA single-strand
      breaks (SSBs) continually produced by endogenous reactive oxygen species or
      exogenous genotoxic agents, typically possess damaged 3'-ends including 3'
      phosphate, 3'-phosphoglycolate, or 3'-alpha, beta-unsaturated aldehyde ends.
      These damaged 3'-ends should be restored to 3'-hydroxyl ends for subsequent
      repair processes. Here we demonstrate by in vitro assay that recombinant human
      aprataxin specifically removes 3'-phosphoglycolate and 3'-phosphate ends at DNA
      3'-ends, but not 3'-alpha, beta-unsaturated aldehyde ends, and can act with DNA
      polymerase beta and DNA ligase III to repair SSBs with these damaged 3'-ends.
      Furthermore, disease-associated mutant forms of aprataxin lack this removal
      activity. The findings indicate that aprataxin has an important role in SSBR,
      that is, it removes blocking molecules from 3'-ends, and that the accumulation of
      unrepaired SSBs with damaged 3'-ends underlies the pathogenesis of EAOH/AOA1. The
      findings will provide new insight into the mechanism underlying degeneration and
      DNA repair in neurons.

PMID- 17519258
TI  - Effect of pulsed magnetic field therapy on pain reported by human volunteers in a
      laboratory model of acute pain.
AB  - BACKGROUND: Pulsed magnetic field therapy (PMFT) is a non-invasive, simple
      technique used extensively for the treatment of muscle pain. However, evidence to
      support its use from well-designed, clinical, or experimental studies is sparse.
      METHODS: We have utilized an acute pain model to perform a randomized, double
      blinded, placebo-controlled, crossover-study on 10 male (18-40 yr) volunteers.
      Pain was elicited by infusion of hypertonic saline 5% into the brachioradialis
      muscle of the non-dominant arm on two occasions, at least 1 week apart. Subjects
      received active or sham PMFT for 30 min in a randomized order delivered by two
      identical, commercially available machines (PulsePack 6000, Quantum Techniks).
      The active machine delivered a M-wave magnetic pulse (1.25 Hz, 3 ms width, 600
      Gauss); the sham device was deactivated and delivered no magnetic energy. Pain
      was assessed at 15-s intervals, and area under the visual analogue score (VAS)
      pain curve (AUCp) was calculated using the trapezoid method. RESULTS: There were
      no significant differences in mean VAS pain scores between the two machines at
      any time. In addition, there were no significant differences with respect to mean
      (sem) maximum pain score [sham 60 (8), active 63 (9) mm; P = 0.66, 95% CI -18 to
      12 mm] or AUCp [sham 463 (50), active 499 (90); P = 0.64, 95% CI -201 to 129].
      CONCLUSIONS: We conclude that, using the electromagnetic characteristics of the
      machine in this study, the PMFT had no effect on pain in our experimental model.
      More work is required to provide an evidence base in support of the use of this
      technique for pain.

PMID- 17519259
TI  - Effect site: who needs it?

PMID- 17519260
TI  - A warning on early-warning scores!

PMID- 17519261
TI  - Multi-level approach to anaesthetic effects produced by sevoflurane or propofol
      in humans: 1. BIS and blink reflex.
AB  - BACKGROUND: The relative roles of forebrain and brainstem in producing adequate
      anaesthesia are unclear. METHODS: We simultaneously analysed the effects of
      sevoflurane (Group S; n = 18) or propofol (Group P; n = 29) on the bispectral
      index (BIS) and the first component of the blink reflex (R1). The dose of
      anaesthetic agent was increased until loss of blink reflex. After discontinuation
      and reappearance of blink reflex activity, the amount was increased again. The
      area under curve R1 (area-R1) of the electromyogram of the orbicularis oculi
      muscle after electrical stimulation of the supraorbital nerve was measured. Using
      a sigmoid E(max) model and a first-order rate constant k(e0), we characterized
      the dose-response relationships for BIS and area-R1. RESULTS: Concentration
      dependent depression of BIS and area-R1 was adequately modelled. The
      concentration that causes an effect midway between minimum and maximum (EC50) for
      area-R1 was smaller than EC50 for BIS in both groups [0.34 (0.19) vs 1.29 (0.19)
      vol% and 1.78 (0.65) vs 2.69 (0.67) mug ml(-1); mean (sd)]. At doses of
      sevoflurane and propofol with equivalent depression of BIS, sevoflurane depressed
      area-R1 more than propofol. The k(e0) for area-R1 was about half that for BIS in
      both groups: 0.24 (0.19-0.29) vs 0.48 (0.38-0.60) min(-1) for Group S; 0.28 (0.23
      0.34) vs 0.46 (0.40-0.54) min(-1) for Group P, geometric mean (95% CI).
      CONCLUSIONS: The blink reflex (brainstem function) is more sensitive to
      sevoflurane or propofol than BIS (forebrain function). Sevoflurane suppresses the
      blink reflex more than propofol. Different k(e0)s for blink reflex vs BIS
      indicate different effect sites.

PMID- 17519262
TI  - Multi-level approach to anaesthetic effects produced by sevoflurane or propofol
      in humans: 2. BIS and tetanic stimulus-induced withdrawal reflex.
AB  - BACKGROUND: General anaesthesia could be assessed at two sites: cortical
      structures and the spinal cord. However, the practicalities of measurement at
      these two sites differ substantially. METHODS: We simultaneously analysed effects
      of sevoflurane (Group S; n = 16) or propofol (Group P; n = 17) on bispectral
      index (BIS) and the tetanic stimulus-induced withdrawal reflex (TIWR). TIWR was
      quantified by the area under the curve of the electromyogram of the biceps
      femoris muscle after electrical stimulation of the sural nerve. After loss of
      consciousness, TIWR was evoked once per minute. The anaesthetic was increased
      until TIWR disappeared. After discontinuation of the anaesthetic and reappearance
      of TIWR, the amount of anaesthetic was increased again. Using a sigmoid E(max)
      model and a first-order rate constant k(e0), we characterized the dose-response
      relationships for BIS and TIWR. RESULTS: Concentration-dependent depression of
      TIWR was reasonably well modelled for sevoflurane, but poorly for propofol. TIWR
      was completely suppressed by sevoflurane, but not propofol. Sevoflurane reduced
      TIWR to 5 mV ms (very weak movement) at 1.68 vol% end-expired concentration
      [approximately minimum alveolar concentration (MAC value)]. The k(e0)s for TIWR
      were smaller than those for BIS: 0.25 (0.16-0.39) vs 0.41 (0.33-0.51) min(-1) for
      Group S; 0.25 (0.22-0.30) vs 0.34 (0.29-0.40) min(-1) for Group P [geometric mean
      (95% CI)]. CONCLUSIONS: High concentrations of sevoflurane depress TIWR more than
      propofol. With propofol, we frequently observed a paradoxical behaviour of
      muscles of the lower leg. TIWR lags behind BIS, indicating different effect sites
      for two intended anaesthetic effects: unresponsiveness to noxious stimulation and
      unconsciousness.

PMID- 17519263
TI  - Iontophoretic transdermal system using fentanyl compared with patient-controlled
      intravenous analgesia using morphine for postoperative pain management.
AB  - BACKGROUND: The fentanyl iontophoretic transdermal system (fentanyl ITS) enables
      needle-free, patient-controlled analgesia for postoperative pain management. This
      study compared the efficacy, safety, and ease of care of fentanyl ITS with
      patient-controlled, i.v. analgesia (PCIA) with morphine for postoperative pain
      management. METHODS: A prospective, randomized, multicentre trial enrolled
      patients in Europe after abdominal or orthopaedic surgery. Patients received
      fentanyl ITS (n = 325; 40.0 microg fentanyl over 10 min) or morphine PCIA [n =
      335; bolus doses (standard at each hospital)] for < or =72 h. Supplemental i.v.
      morphine was available during the first 3 h. The primary efficacy measure was the
      patient global assessment (PGA) of the pain control method during the first 24 h.
      RESULTS: PGA ratings of 'good' or 'excellent' were reported by 86.2 and 87.5% of
      patients using fentanyl ITS or morphine PCIA, respectively (95% CI, -6.5 to
      3.9%). Mean (sd) last pain intensity scores (numerical rating scale, 0-10) were
      1.8 (1.77) and 1.9 (1.86) in the fentanyl ITS and morphine PCIA groups,
      respectively (95% CI, -0.38 to 0.18). More patients reported a system-related
      problem for fentanyl ITS than morphine PCIA (51.1 vs 17.9%, respectively).
      However, fewer of these problems interrupted pain control (4.4 vs 41.3%,
      respectively). Patients, nurses, and physiotherapists reported more favourable
      overall ease-of-care ratings for fentanyl ITS than morphine PCIA. Study
      termination rates and opioid-related side-effects were similar between groups.
      CONCLUSION: Fentanyl ITS and morphine PCIA were comparably effective and safe.

PMID- 17519264
TI  - Successful management of patients with a drug-eluting coronary stent presenting
      for elective surgery.

PMID- 17519265
TI  - Effects of hydroxyethyl starch in critically ill patients.

PMID- 17519266
TI  - Pain relief after thoracotomy.

PMID- 17519267
TI  - Synthetic oxytocin and latex allergy.

PMID- 17519268
TI  - Phasic voltage ECG variation during laparoscopy.

PMID- 17519269
TI  - Epidural anaesthesia and stress-induced immunosuppression.

PMID- 17519271
TI  - Elevated relapse rate under oral methotrexate versus leflunomide for maintenance
      of remission in Wegener's granulomatosis.
AB  - OBJECTIVES: Results from open-label trials suggest that methotrexate (MTX) and
      leflunomide (LEF) are effective for maintenance of remission in Wegener's
      granulomatosis (WG), but data from randomized controlled clinical trails are not
      yet available. METHODS: In this multicentre, prospective randomized controlled
      clinical trial, patients with generalized WG were treated either with oral LEF 30
      mg/day or oral MTX (starting with 7.5 mg/week reaching 20 mg/week after 8 weeks)
      for 2 yrs following induction of remission with cyclophosphamide. The primary
      endpoint was the incidence of relapses. Secondary outcome parameters were DEI,
      BVAS, SF-36, cANCA-titre, ESR and CRP. RESULTS: Fifty-four patients were included
      in the study, 26 in the LEF-limb, 28 in the MTX-limb. In the LEF-group, six
      patients relapsed after a median time of 7 months, thereof one major relapse with
      a new pulmonary manifestation. In the MTX-group, 13 relapses occurred in 6
      months, of which seven were major: rapidly progressive glomerulonephritis (n =
      4), pulmonary haemorrhage (n = 2) and one cerebral granuloma. The significantly
      higher incidence of major relapses in the MTX-limb (P = 0.037) led to premature
      termination of the study. In the LEF-limb, four patients were withdrawn due to
      hypertension (n = 2), peripheral neuropathy (n = 1) and leucopenia (n = 1).
      CONCLUSION: LEF at a dosage of 30 mg/day appears to be effective in the
      prevention of major relapses in WG, however, this is associated with an increased
      frequency of adverse events. Further studies testing other dosing regimens of
      lower doses of LEF are needed to confirm these promising results in larger
      patients cohorts.

PMID- 17519272
TI  - Varus instability of the hallux interphalangeal joint in a taekwondo athlete.
AB  - The hallux interphalangeal joint is stable in the transverse plane and there have
      been only a few reports of varus instability of this joint. A case is described
      of varus subluxation of the hallux interphalangeal joint in a taekwondo athlete
      and the surgical outcome after reconstruction of the collateral ligament.
      Taekwondo athletes, who require fast powerful kicks, should be warned about this
      type of forefoot injury.

PMID- 17519274
TI  - Upper limits for exceedance probabilities under the one-way random effects model.
AB  - In this article, we propose statistical methods for setting upper limits on (i)
      the probability that the mean exposure of an individual worker exceeds the
      occupational exposure limit (OEL) and (ii) the probability that the exposure of a
      worker exceeds the OEL. The proposed method for (i) is obtained using the
      generalized variable approach, and the one for (ii) is based on an approximate
      method for constructing one-sided tolerance limits in the one-way random effects
      model. Even though tolerance limits can be used to assess the proportion of
      exposure measurements exceeding the OEL, the upper limits on these probabilities
      are more informative than tolerance limits. The methods are conceptually as well
      as computationally simple. Two data sets involving industrial exposure data are
      used to illustrate the methods.

PMID- 17519275
TI  - Evaluation of a proposed velocity equation for improved exothermic process
      control.
AB  - Exothermic or heated processes create potentially unsafe work environments for an
      estimated 5-10 million American workers each year. Excessive heat and process
      contaminants have the potential to cause adverse health effects in exposed
      workers. Owing to the potential hazards, engineering controls are recommended for
      these processes. Our understanding of heat transfer and meteorological theories,
      and their applications for engineering controls have evolved since seminal work
      was published by Hemeon in 1955. These refined theories were reviewed and used to
      develop a proposed equation to estimate buoyant plume mean velocity. Mean
      velocity is a key parameter used to estimate the plume volumetric flow required
      for controlling effluents from exothermic processes. Subsequent to developing the
      proposed equation, plume velocity data were collected with a thermal anemometer
      for a model exothermic process in the laboratory, and an actual exothermic
      process in the field. Laboratory and field results were then compared to
      solutions provided by the proposed, American Conference of Governmental
      Industrial Hygienists (ACGIH), and Hemeon mean velocity equations. To determine
      which equation most closely matched the laboratory and field data, either t-tests
      or Wilcoxon Signed Rank tests were conducted (based on examination of data
      normality) to determine the difference between collected data and solutions from
      the proposed, ACGIH, and Hemeon equations. Median differences and P-values from
      Wilcoxon Signed Rank tests (nonparametric) indicate that the ACGIH mean velocity
      equation provides significantly different estimates from the laboratory and the
      field mean velocity data. However, the proposed and Hemeon equation provided
      solutions that were not significantly different from the collected data. These
      results were unexpected due to the similar developmental backgrounds between the
      ACGIH and Hemeon equations. Findings indicate that radiant heat flux is an
      important consideration when using horizontal plate heat transfer equations to
      estimate plume mean velocity over the range of parameters investigated. Results
      indicate that the mean velocity equation currently recommended by ACGIH is not as
      accurate as either the proposed or Hemeon equations over the range of parameters
      investigated.

PMID- 17519276
TI  - Survival and causes of death in 366 Hungarian patients with systemic sclerosis.
AB  - OBJECTIVE: Survival analysis of a series of 366 consecutive patients with
      systemic sclerosis (SSc). METHODS: Clinical and laboratory data were evaluated
      from 1983 until 2005 using a standard protocol. The female/male ratio was 315/51.
      The mean (SD) age of the patients was 56.8 (12.2) years. The duration of disease
      was 12 (5-19) years with a median follow-up of 6 (3-12) years. RESULTS: Kaplan
      Meier univariate analysis showed that renal, cardiac involvement, pigmentation
      disturbances, malabsorption, a forced vital capacity <50%, diffuse scleroderma,
      presence of early malignancy, anaemia, and increased erythrocyte sedimentation
      rate (ESR) were signs of unfavourable prognosis, whereas anti-centromere
      antibodies were indicators of a good survival. In the multivariate Cox
      proportional hazards model the presence of diffuse scleroderma, renal
      involvement, coexistence of a malignant disease, and increased ESR were poor
      independent prognostic signs. Elderly age at the onset of disease also caused an
      unfavourable outcome. A total of 86 SSc-related deaths were recorded during the
      follow-up. Of them, 65% were attributed to cardiorespiratory manifestation of
      disease. Tumour associated early death was found in 12 cases (14%). CONCLUSIONS:
      In addition to the well-known factors influencing the outcome (diffuse subset,
      internal organ involvements, and inflammatory signs), the coexistence of
      scleroderma with a malignancy also causes a poor outcome.

PMID- 17519277
TI  - BILAG-2004 index captures systemic lupus erythematosus disease activity better
      than SLEDAI-2000.
AB  - OBJECTIVE: To assess the reliability of Systemic Lupus Erythematosus Disease
      Activity Index (SLEDAI)-2000 index in routine practice and its ability to capture
      disease activity as compared with the British Isles Lupus Assessment Group
      (BILAG)-2004 index. METHODS: Patients with systemic lupus erythematosus from 11
      centres were assessed separately by two raters in routine practice. Disease
      activity was assessed using the BILAG-2004 and SLEDAI-2000 indices. The level of
      agreement for items was used to assess the reliability of SLEDAI-2000. The
      ability to detect disease activity was assessed by determining the number of
      patients with a high activity on BILAG-2004 (overall score A or B) but low SLEDAI
      2000 score (<6) and number of patients with low activity on BILAG-2004 (overall
      score C, D or E) but high SLEDAI-2000 score (>or=6). Treatment of these patients
      was analysed, and the increase in treatment was used as the gold standard for
      active disease. RESULTS: 93 patients (90.3% women, 69.9% Caucasian) were studied:
      mean age was 43.8 years, mean disease duration 10 years. There were 43 patients
      (46.2%) with a difference in SLEDAI-2000 score between the two raters and this
      difference was >or=4 in 19 patients (20.4%). Agreement for each of the items in
      SLEDAI-2000 was between 81.7 and 100%. 35 patients (37.6%) had high activity on
      BILAG-2004 but a low SLEDAI-2000 score, of which 48.6% had treatment increased.
      There were only five patients (5.4%) with low activity on BILAG-2004 but a high
      SLEDAI-2000 score. CONCLUSIONS: SLEDAI-2000 is a reliable index to assess
      systemic lupus erythematosus disease activity but it is less able than the BILAG
      2004 index to detect active disease requiring increased treatment.

PMID- 17519278
TI  - Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for
      remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an
      open-label strategy trial).
AB  - BACKGROUND: To investigate whether intensive treatment with methotrexate (MTX)
      according to a strict protocol and a computerised decision program is more
      beneficial compared to conventional treatment with MTX in early rheumatoid
      arthritis. METHODS: In a two-year multicentre open label strategy trial, 299
      patients with early rheumatoid arthritis were randomly assigned to the intensive
      strategy group or the conventional strategy group. Patients in both groups
      received MTX, the aim of treatment being remission. Patients in the intensive
      treatment group came to the outpatient clinic once every month; adjustment of the
      MTX dosage was tailored to the individual patient on the basis of predefined
      response criteria, using a computerised decision program. Patients of the
      conventional strategy group came to the outpatient clinic once every three
      months; they were treated according to common practice. Cyclosporine was added if
      patients had an inadequate response to maximal tolerated MTX doses. RESULTS:
      Seventy six (50%) patients in the intensive strategy group achieved at least one
      period of remission during the two year trial, versus 55 patients (37%) in the
      conventional strategy group (p = 0.03). Areas under the curve for nearly all
      clinical variables were significantly lower-that is, there was a better clinical
      effect for the intensive treatment group compared with the conventional treatment
      group. CONCLUSION: The results of this study show that it is possible to
      substantially enhance the clinical efficacy early in the course of the disease by
      intensifying treatment with MTX, aiming for remission, tailored to the individual
      patient. Furthermore, participating rheumatologists indicated that the
      computerised decision program could be a helpful tool in their daily clinical
      practice.

PMID- 17519279
TI  - Both mammalian PIG-M and PIG-X are required for growth of GPI14-disrupted yeast.
AB  - GPI mannosyltransferase I (GPI-MT-I) transfers the first mannose to a GPI-anchor
      precursor, glucosamine-(acyl)phosphatidylinositol [GlcN-(acyl)PI]. Mammalian GPI
      MT-I consists of two components, PIG-M and PIG-X, which are homologous to Gpi14p
      and Pbn1p in Saccharomyces cerevisiae, respectively. In the present study, we
      disrupted yeast GPI14 and analysed the phenotype of gpi14 yeast. The gpi14
      haploid cells were inviable and accumulated GlcN-(acyl)PI. We cloned PIG-M
      homologues from human, Plasmodium falciparum (PfPIG-M) and Trypanosoma brucei
      (TbGPI14), and tested whether they could complement gpi14-disrupted yeast. None
      of them restored GPI-MT-I activity and cell growth in gpi14-disrupted yeast.
      However, gpi14-disrupted yeast cells with human PIG-M, but not with PfPIG-M or
      TbGPI14, grew slowly but significantly when they were supplemented with rat PIG
      X. This suggests that the association of PIG-X and PIG-M for GPI-MT-I activity is
      not interchangeable between mammals and the other lower eukaryotes.

PMID- 17519280
TI  - Expression of c-Kit receptor tyrosine kinase and effect on beta-cell development
      in the human fetal pancreas.
AB  - The receptor, c-Kit, and its ligand, stem cell factor (SCF), are critical for
      hematopoietic stem cell differentiation and have been implicated in the
      development, function, and survival of rodent islets. Previously, we reported
      that exogenous SCF treatments of cultured human fetal (14-16 wk fetal age) islet
      epithelial clusters enhanced islet cell differentiation and proliferation (Li J,
      Goodyer CG, Fellows F, Wang R. Int J Biochem Cell Biol 38: 961-972, 2006). In the
      present study, we examined the expression pattern of c-Kit in early to
      midgestation human fetal pancreata and the relevance of c-Kit receptor tyrosine
      kinase for insulin gene expression and beta-cell survival. c-Kit is expressed in
      the intact pancreas in a cell-specific manner, with a significant decrease in
      immunoreactivity in the duct regions from 8 to 21 wk fetal age, paralleled by a
      significant increase in expression within endocrine regions. These c-Kit-positive
      cells are highly proliferative and show frequent coexpression with insulin and
      glucagon. Treatment of islet-epithelial clusters with anti-ACK45 antibody
      stimulates c-Kit phosphorylation paralleled by a significant increase in PDX-1
      and insulin expression, increased cell proliferation, and reduced beta-cell
      death. In contrast, transient transfection with c-Kit siRNA results in a three-
      to fourfold decrease in c-Kit, PDX-1, and insulin expression and decreased cell
      proliferation. This study describes important changes in the distribution and
      dynamics of c-Kit-expressing cells during human fetal pancreatic neogenesis,
      suggesting that c-Kit may be a marker for human pancreatic islet progenitor
      cells. Functional analysis of the c-Kit receptor tyrosine kinase provides
      evidence that phosphorylation of c-Kit receptor may be involved in mediating
      early beta-cell differentiation and survival.

PMID- 17519281
TI  - Calculating glucose fluxes during meal tolerance test: a new computational
      approach.
AB  - A new calculation method is proposed to quantify the endogenous glucose
      production (EGP), the glucose appearance rate due to meal ingestion (R(a meal)),
      and the glucose disposal (R(d)) during a three-tracer study design. The method
      utilizes the maximum likelihood theory combined with a regularization method to
      achieve a theoretically coherent computational framework. The method uses the two
      compartment formulation of the glucose kinetics. Instead of assuming smoothness
      of unlabeled and labeled glucose concentrations, the method assumes that the EGP,
      the R(a meal), and the fractional glucose clearance are smooth, increasing
      plausibility of their individual estimates. The method avoids transformation of
      the measurement errors, which may skew the estimates of the EGP, R(a meal), and
      R(d) with the traditional approach. Finally, the sequential nature of the
      calculations is replaced by calculating the EGP, R(a meal), and R(d) in "one go"
      to avoid the propagation of the errors from the EGP and R(a meal) into R(d). An
      example study is shown demonstrating the utility of the approach. A better
      performance of the new method is demonstrated in a simulation study.

PMID- 17519282
TI  - Palmitate modulates intracellular signaling, induces endoplasmic reticulum
      stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes.
AB  - Although fatty acids enhance preadipocyte differentiation in the presence of
      adequate hormone cocktails, little is known regarding their effects in the
      absence of these hormones. We have now shown that palmitate, a common long-chain
      saturated fatty acid, induced apoptosis in both mouse 3T3-L1 and rat primary
      preadipocytes grown in a normal serum-containing medium. Treatment of
      preadipocytes with palmitate induced multiple endoplasmic reticulum (ER) stress
      responses, evidenced by increased protein content of CHOP and GRP78 and splicing
      of XBP-1 mRNA, as well as altered phosphorylation of eIF2alpha and increased
      phosphorylation of JNK and Erk1/2. Intriguingly, palmitate induced an early
      activation of Akt but diminished both Akt activation and its protein mass after
      prolonged incubation (>6 h). In association with these changes, palmitate reduced
      expression of beta-catenin and its downstream target, c-Myc and cyclin D1, two
      key prosurvival proteins. Overexpression of constitutively active Akt did not
      block the apoptotic effect of palmitate. Cotreatment with unsaturated fatty acids
      (oleate, linoleate) or with LiCl (a glycogen synthase kinase-3beta inhibitor)
      attenuated the palmitate-induced apoptosis. Subsequent analysis suggested that
      the unsaturated fatty acids probably counteracted palmitate by reducing, not
      eliminating, ER stress, whereas LiCl probably improved viability by activating
      the Wnt signaling pathway. Cotreatment of palmitate with a standard adipogenic
      hormone cocktail also abolished the apoptotic effect and promoted adipocyte
      differentiation. Collectively, our results suggest that palmitate causes multiple
      cellular stresses that may lead to apoptosis in preadipocytes in the absence of
      adipogenic stimuli, highlighting the importance of exogenous hormones in
      directing cell fate in response to increased fatty acid influx.

PMID- 17519283
TI  - Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts
      cardioprotective effect of GIK.
AB  - There is a close association between hyperglycemia and increased risk of
      mortality after acute myocardial infarction (AMI). However, whether acute
      hyperglycemia exacerbates myocardial ischemia/reperfusion (MI/R) injury remains
      unclear. We observed the effects of acute hyperglycemia on MI/R injury and on the
      cardioprotective effect of glucose-insulin-potassium (GIK). Male rats were
      subjected to 30 min of myocardial ischemia and 6 h of reperfusion. Rats were
      randomly received one of the following treatments (at 4 ml.kg(-1).h(-1) iv):
      Vehicle, GIK (GIK during reperfusion; glucose: 200g/l, insulin: 60 U/l, KCL: 60
      mmol/l), HG (high glucose during ischemia; glucose:500 g/l), GIK + HG (HG during
      I and GIK during R) or GIK + wortmannin (GIK during R and wortmannin 15 min
      before R). Blood glucose, plasma insulin concentration and left ventricular
      pressure (LVP) were monitored throughout the experiments. Hyperglycemia during
      ischemia not only significantly increased myocardial apoptosis (23.6 +/- 1.7% vs.
      18.8 +/- 1.4%, P < 0.05 vs. vehicle), increased infarct size (IS) (45.6 +/- 3.0%
      vs. 37.6 +/- 2.0%, P < 0.05 vs. vehicle), decreased Akt and GSK-3beta
      phosphorylations (0.5 +/- 0.2 and 0.6 +/- 0.1% fold of vehicle, respectively, P <
      0.05 vs. vehicle) following MI/R, but almost completely blocked the
      cardioprotective effect afforded by GIK, as evidenced by significantly increased
      apoptotic index (19.1 +/- 2.0 vs. 10.3 +/- 1.2%, P < 0.01 vs. GIK), increased
      myocardial IS (39.2 +/- 2.8 vs. 27.2 +/- 2.1%, P < 0.01 vs. GIK), decreased Akt
      phosphorylation (1.1 +/- 0.1 vs. 1.7 +/- 0.2%, P < 0.01 vs. GIK) and GSK-3beta
      phosphorylation (1.4 +/- 0.2 vs. 2.3 +/- 0.2%, P < 0.05 vs. GIK). Hyperglycemia
      significantly exacerbates MI/R injury and blocks the cardioprotective effect
      afforded by GIK, which is, at least in part, due to hyperglycemia-induced
      decrease of myocardial Akt activation.

PMID- 17519284
TI  - Metabolic challenges reveal impaired fatty acid metabolism and translocation of
      FAT/CD36 but not FABPpm in obese Zucker rat muscle.
AB  - We examined, in muscle of lean and obese Zucker rats, basal, insulin-induced, and
      contraction-induced fatty acid transporter translocation and fatty acid uptake,
      esterification, and oxidation. In lean rats, insulin and contraction induced the
      translocation of the fatty acid transporter FAT/CD36 (43 and 41%, respectively)
      and plasma membrane-associated fatty acid binding protein (FABPpm; 19 and 60%)
      and increased fatty acid uptake (63 and 40%, respectively). Insulin and
      contraction increased lean muscle palmitate esterification and oxidation 72 and
      61%, respectively. In obese rat muscle, basal levels of sarcolemmal FAT/CD36
      (+33%) and FABPpm (+14%) and fatty acid uptake (+30%) and esterification (+32%)
      were increased, whereas fatty acid oxidation was reduced (-28%). Insulin
      stimulation of obese rat muscle increased plasmalemmal FABPpm (+15%) but not
      plasmalemmal FAT/CD36, blunted fatty acid uptake and esterification, and failed
      to reduce fatty acid oxidation. In contracting obese rat muscle, the increases in
      fatty acid uptake and esterification and FABPpm translocation were normal, but
      FAT/CD36 translocation was impaired and fatty acid oxidation was blunted. There
      was no relationship between plasmalemmal fatty acid transporters and palmitate
      partitioning. In conclusion, fatty acid metabolism is impaired at several levels
      in muscles of obese Zucker rats; specifically, they are 1) insulin resistant with
      respect to FAT/CD36 translocation and fatty acid uptake, esterification, and
      oxidation and 2) contraction resistant with respect to fatty acid oxidation and
      FAT/CD36 translocation, but, conversely, 3) obese muscles are neither insulin nor
      contraction resistant at the level of FABPpm. Finally, 4) there is no evidence
      that plasmalemmal fatty acid transporters contribute to the channeling of fatty
      acids to specific metabolic destinations within the muscle.

PMID- 17519285
TI  - Cdk1 phosphorylation sites on Cdc27 are required for correct chromosomal
      localisation and APC/C function in syncytial Drosophila embryos.
AB  - Anaphase-promoting complex or cyclosome (APC/C) controls the metaphase-to
      anaphase transition and mitosis exit by triggering the degradation of key cell
      cycle regulators such as securin and B-type cyclins. However, little is known
      about the functions of individual APC/C subunits and how they might regulate
      APC/C activity in space and time. Here, we report that two potential Cdk1 kinase
      phosphorylation sites are required for the chromosomal localisation of GFP::Cdc27
      during mitosis. Either or both of the highly conserved proline residues in the
      Cdk1 phosphorylation consensus sequence motifs were mutated to alanine (Cdc27
      P304A or P456A). The singly mutated fusion proteins, GFP::Cdc27P304A and
      GFP::Cdc27P456A, can still localise to mitotic chromosomes in a manner identical
      to wild-type GFP::Cdc27 and are functional in that they can rescue the phenotype
      of the cdc27L7123 mutant in vivo. However, when both of the Cdk1 phosphorylation
      sequence motifs were mutated, the resulting GFP::Cdc27P304A,P456A construct was
      not localised to the chromosomes during mitosis and was no longer functional, as
      it failed to rescue mutant phenotypes of the cdc27L7123 gene. High levels of
      cyclin B and cyclin A were detected in mutant third instar larvae brain samples
      compared with its wild-type control. These results show for the first time that
      the two potential Cdk1 phosphorylation sites on Drosophila Cdc27 are required for
      its chromosomal localisation during mitosis and imply that these localisations
      specific to Cdc27 are crucial for APC/C functions.

PMID- 17519286
TI  - Identification of novel chromatin-associated proteins involved in programmed
      genome rearrangements in Tetrahymena.
AB  - Extensive DNA rearrangements occur during the differentiation of the developing
      somatic macronuclear genome from the germ line micronuclear genome of Tetrahymena
      thermophila. To identify genes encoding proteins likely to be involved in this
      process, we devised a cytological screen to find proteins that specifically
      localize in macronuclear anlagen (Lia proteins) at the stage when rearrangements
      occur. We compared the localization of these with that of the chromodomain
      protein, Pdd1p, which is the most abundant known participant in this genome
      reorganization. We show that in live cells, Pdd1p exhibits dynamic localization,
      apparently shuttling from the parental to the developing nuclei through
      cytoplasmic bodies called conjusomes. Visualization of GFP-tagged Pdd1p also
      highlights the substantial three-dimensional nuclear reorganization in the
      formation of nuclear foci that occur coincident with DNA rearrangements. We found
      that late in macronuclear differentiation, four of the newly identified proteins
      are organized into nuclear foci that also contain Pdd1p. These Lia proteins are
      encoded by primarily novel genes expressed at the beginning of macronuclear
      differentiation and have properties or recognizable domains that implicate them
      in chromatin or nucleic acid binding. Three of the Lia proteins also localize to
      conjusomes, a result that further implicates this structure in the regulation of
      DNA rearrangement.

PMID- 17519287
TI  - Chitin synthase III requires Chs4p-dependent translocation of Chs3p into the
      plasma membrane.
AB  - In Saccharomyces cerevisiae, Chs4p is required for chitin synthase III (CSIII)
      activity and hence for chitin synthesis. This protein is transported in vesicles
      in a polarized fashion independently of the other Chs proteins. Its association
      with membranes depends not only on prenylation, but also on its interaction with
      other proteins, mainly Chs3p, which is the catalytic subunit of CSIII and is able
      to properly direct Chs4p to the bud neck in the absence of prenylation. Chs4p is
      present in functionally limiting amounts and its overexpression increases Chs3p
      accumulation at the plasma membrane with a concomitant increase in chitin
      synthesis. In the absence of Chs4p, Chs3p is delivered to the plasma membrane but
      fails to accumulate there because it is rapidly endocytosed and accumulates in
      intracellular vesicles. A blockade of endocytosis stops Chs3p internalization,
      triggering a significant increase in chitin synthesis. This blockade is
      independent of Chs4p function, allowing the accumulation of Chs3p at the plasma
      membrane even in the chs4Delta mutant. However, the absence of Chs4p renders
      CSIII functionally inactive, independently of Chs3p accumulation at the plasma
      membrane. Chs4p thus promotes Chs3p translocation into the plasma membrane in a
      stable and active form. Proper CSIII turnover is maintained through the endocytic
      internalization of Chs3p.

PMID- 17519288
TI  - Nuclear localization of barrier-to-autointegration factor is correlated with
      progression of S phase in human cells.
AB  - Barrier-to-autointegration factor (BAF) is a conserved metazoan protein that
      plays a critical role in retrovirus infection. To elucidate its role in
      uninfected cells, we first examined the localization of BAF in both mortal and
      immortal or cancerous human cell lines. In mortal cell lines (e.g. TIG-1, WI-38
      and IMR-90 cells) BAF localization depended on the age of the cell, localizing
      primarily in the nucleus of >90% of young proliferating cells but only 20-25% of
      aged senescent cells. In immortal cell lines (e.g. HeLa, SiHa and HT1080 cells)
      BAF showed heterogeneous localization between the nucleus and cytoplasm. This
      heterogeneity was lost when the cells were synchronized in S phase. In S-phase
      synchronized populations, the percentage of cells with predominantly nuclear BAF
      increased from 30% (asynchronous controls) to approximately 80%. In HeLa cells,
      RNAi-induced downregulation of BAF significantly increased the proportion of
      early S-phase cells that retained high levels of cyclin D3 and cyclin E
      expression and slowed progression through early S phase. BAF downregulation also
      caused lamin A to mislocalize away from the nuclear envelope. These results
      indicate that BAF is required for the integrity of the nuclear lamina and normal
      progression of S phase in human cells.

PMID- 17519290
TI  - Maturing of pharmaceutical education. 1976.

PMID- 17519291
TI  - Setting a solid pharmacy foundation.

PMID- 17519292
TI  - Lubiprostone: a chloride channel activator for treatment of chronic constipation.
AB  - OBJECTIVE: To review lubiprostone's pharmacology, pharmacokinetics, efficacy, and
      safety in the treatment of chronic constipation. DATA SOURCES: A literature
      search was conducted using PubMed/MEDLINE (1966-January 2007), IngentaConnect,
      and International Pharmaceutical Abstracts (1977-January 2007). Key words used
      included lubiprostone, Amitiza, and chronic constipation. STUDY SELECTION AND
      DATA EXTRACTION: All articles identified from the data sources that were
      published in English were evaluated. DATA SYNTHESIS: Lubiprostone is a chloride
      channel activator approved by the Food and Drug Administration for the treatment
      of chronic constipation. A randomized, double-blind, parallel-group, placebo
      controlled study evaluating the effect of lubiprostone on gastric function showed
      slowed gastric emptying and increased small bowel and colonic transit time. Peak
      plasma concentration was shown to be around 1.14 hours, with a majority of the
      drug excreted in the urine within 48 hours. Phase III trials have noted that most
      patients with chronic constipation have a spontaneous bowel movement within 24
      hours after taking lubiprostone. The most common adverse events in these trials
      were nausea, diarrhea, abdominal pain, and headache. Lubiprostone use has not
      been studied in the pediatric population. CONCLUSIONS: Lubiprostone may be a
      reasonable alternative for use in patients who either fail or are intolerant of
      standard therapy for chronic constipation. Head-to-head comparison studies with
      conventional therapy are needed to contrast clinical efficacy and safety of this
      medication.

PMID- 17519293
TI  - Evolution of peroxisome proliferator-activated receptor agonists.
AB  - OBJECTIVE: To discuss the evolution of peroxisome proliferator-activated receptor
      (PPAR) agonists from single site to multiple subtype or partial agonists for the
      treatment of type 2 diabetes, dyslipidemia, obesity, and the metabolic syndrome.
      DATA SOURCES: Information was obtained from MEDLINE (1966-March 2007) using
      search terms peroxisome proliferator-activated receptor agonist, PPAR dual
      agonist, PPAR alpha/gamma agonist, PPAR pan agonist, partial PPAR, and the
      specific compound names. Other sources included pharmaceutical companies, the
      Internet, and the American Diabetes Association 64th-66th Scientific Sessions
      abstract books. STUDY SELECTION AND DATA EXTRACTION: Animal data, abstracts,
      clinical trials, and review articles were reviewed and summarized. DATA
      SYNTHESIS: PPAR alpha, gamma, and delta receptors play an important role in lipid
      metabolism, regulation of adipocyte proliferation and differentiation, and
      insulin sensitivity. The PPAR dual agonists were developed to combine the
      triglyceride lowering and high-density lipoprotein cholesterol elevation from the
      PPAR-alpha agonists (fibrates) with the insulin sensitivity improvement from the
      PPAR-gamma agonists (thiazolidinediones). Although the dual agonists reduced
      hemoglobin A(1C) (A1C) and improved the lipid profile, adverse effects led to
      discontinued development. Currently, PPAR-delta agonists (GW501516 in Phase I
      trials), partial PPAR-gamma agonists (metaglidasen in Phase II and III trials),
      and pan agonists (alpha, gamma, delta; netoglitazone in Phase II and III trials)
      with improved cell and tissue selectivity are undergoing investigation to address
      multiple aspects of the metabolic syndrome with a single medication. By
      decreasing both A1C and triglycerides, metaglidasen did improve multiple aspects
      of the metabolic syndrome with fewer adverse effects than compared with placebo.
      Metaglidasen is now being compared with pioglitazone. CONCLUSIONS: Influencing
      the various PPARs results in improved glucose, lipid, and weight management, with
      effects dependent on full or partial agonist activity at single or multiple
      receptors. Although the dual PPAR compounds have been associated with
      unacceptable toxicities, new PPAR agonist medications continue to be developed
      and investigated to discover a safe drug with benefits in multiple disease
      states.

PMID- 17519294
TI  - Vitamin C pharmacokinetics after continuous infusion in a patient with prostate
      cancer.

PMID- 17519295
TI  - Evaluation of consultation in community pharmacies with mystery shoppers.
AB  - BACKGROUND: Consultation of patients in community pharmacies (CPs) must meet
      standards, especially in selling over-the-counter drugs; however, there has been
      no information as to whether northeastern German CPs meet these standards.
      OBJECTIVE: To estimate aspects of consultation quality in CPs in Mecklenburg
      Vorpommern, located in northeastern Germany, study factors related to
      consultation quality, and check compliance with Pharmacy Practice Law, because
      not all pharmaceutical professions may legally sell drugs. METHODS: In 2005, 6
      mystery shoppers (pharmacy students) presented with a headache to 146 of 398 CPs;
      they requested a sleeping pill plus an antihistaminic drug and completed data
      collection forms. Consultation scores were calculated and effects of
      pharmacy/staff characteristics on consultation were modeled with linear
      (consultation score) and logistic regression (failure to detect a drug-drug
      interaction). Variables used in models were staff profession, pharmacy size
      (number of staff), city/town size (number of pharmacies), and day of the week in
      which shoppers visited the pharmacy. RESULTS: Despite a high willingness of
      pharmacy staff to provide consultation (83% spontaneously offered advice),
      northeastern German CPs did not achieve their professional mission. Extreme
      variation was evident in their questioning of the mystery shoppers regarding use
      of important single items (from 1% for pregnancy/breast-feeding considerations to
      56% for dosing instructions). In all cases, drugs were sold to the shoppers; most
      (91%) were single agents. Drug-drug interaction detection was low: 43 (30%)
      counselors informed mystery shoppers about the interaction. The profession of the
      consulting staff and the size of the pharmacy were associated with consultation
      quality (highest for pharmacists; lowest for small pharmacies [2-4 staff]). For
      interaction detection, consulting staff profession was relevant: pharmacists had
      OR of 3.2 for the detection compared with pharmacy engineers/assistants. In 7
      pharmacies, staff illegally sold drugs to customers. CONCLUSIONS: Northeastern
      German CPs have much need and potential for improvement in consultation quality
      and drug-drug interaction detection. In-depth elicitation of symptoms and details
      of patients' situations must be improved. Relevant training should be provided,
      including use of software to identify drug interactions. Mystery shopper studies
      give valuable information for tailoring training schemes.

PMID- 17519296
TI  - Tigecycline: a novel broad-spectrum antimicrobial.
AB  - OBJECTIVE: To review the literature on tigecycline, a novel antibiotic. DATA
      SOURCES: References were identified through MEDLINE (1966-February 2007) and
      International Pharmaceutical Abstracts (1970-February 2007) databases, using the
      key words tigecycline, glycylcycline, complicated skin and skin structure
      infections (cSSSI), complicated intraabdominal infections (cIAI), and in vitro.
      Additional articles for this review were identified by reviewing the
      bibliographies of articles cited. The package insert was also used as a
      reference. STUDY SELECTION AND DATA EXTRACTION: In vitro, clinical, and
      pharmacokinetic studies evaluating tigecycline's safety and efficacy were
      selected. DATA SYNTHESIS: A tigecycline 100 mg intravenous loading dose followed
      by an intravenous infusion of 50 mg every 12 hours was shown in clinical trials
      to be as effective as comparator antibiotics in treating cSSSI and cIAI.
      Tigecycline has a broad spectrum of activity that includes many resistant
      bacteria with few treatment options, such as methicillin-resistant Staphylococcus
      aureus and extended-spectrum beta-lactamase-producing bacteria such as
      Escherichia coli and Klebsiella pneumoniae. In cSSSI studies, tigecycline was
      found to be noninferior to vancomycin plus aztreonam with test-of-cure rates of
      86.5% and 88.6%, respectively. Tigecycline was also found to be noninferior to
      imipenem/cilastatin in cIAI studies; clinical cure rates were 86.1% and 86.2%,
      respectively. In vitro activity has been demonstrated against other multidrug
      resistant microorganisms of concern, such as Acinetobacter spp. Although it has a
      broad spectrum of activity, tigecycline has inadequate activity against
      Pseudomonas spp. Nausea and vomiting were the most frequently reported adverse
      effects. CONCLUSIONS: Tigecycline is approved for the treatment of cSSSI and cIAI
      infections. To date, little resistance to tigecycline has been reported; however,
      with widespread use of the drug, resistance will likely occur. Since published
      studies have not dealt with seriously ill patients, it is recommended that, until
      further studies have been completed, other agents be used in the treatment of
      these patients unless no option other than tigecycline exists.

PMID- 17519297
TI  - Modafinil augmentation for residual symptoms of fatigue in patients with a
      partial response to antidepressants.
AB  - OBJECTIVE: To evaluate the literature discussing the use of modafinil in the
      treatment of residual symptoms of fatigue in patients with depression. DATA
      SOURCES: PubMed (1966-March 2007) and International Pharmaceutical Abstracts
      (1970-March 2007) were searched using the key words modafinil and depression. A
      manual search of the reference section of the articles retrieved was conducted to
      identify articles not indexed in either of these sources. STUDY SELECTION AND
      DATA EXTRACTION: All articles published in English were evaluated. Studies were
      included if modafinil was used to treat patients with residual fatigue from
      depression and the effects were measured with validated fatigue subscales. DATA
      SYNTHESIS: One retrospective study, 5 open-label trials, and 2 randomized
      controlled clinical trials met the inclusion criteria for assessment of residual
      symptoms of fatigue as assessed by commonly used fatigue subscales after
      modafinil administration. Although improvement with fatigue has occurred with
      modafinil therapy, literature regarding the topic is limited by the lack of well
      controlled clinical trials. Modafinil does appear to improve residual fatigue
      with depression as evidenced by open-label trials; however, the efficacy of this
      agent has not been duplicated in randomized controlled trials. The open-label
      trials that have been conducted often had no comparator and a small number of
      patients. In addition, outcome measures used in the studies were not consistent
      between trials. Modafinil appears to be well tolerated, with the main adverse
      effects being headache and nausea. CONCLUSIONS: Open-label trials indicate that
      modafinil may be effective in ameliorating fatigue associated with depression;
      however, this effect has not been reproduced in randomized, double-blind, placebo
      controlled clinical trials. Therefore, the use of modafinil for the treatment of
      residual fatigue is not recommended due to the lack of reproducible data of its
      efficacy. Long-term, adequately powered clinical trials should be conducted to
      determine its place in therapy.

PMID- 17519298
TI  - Extended-release venlafaxine-induced alopecia.

PMID- 17519299
TI  - Assessing the validity of self-reported medication adherence in hepatitis C
      treatment.
AB  - OBJECTIVE: To assess the validity of self-reported medication adherence provided
      by individuals in treatment for hepatitis C virus (HCV) infection with a regimen
      of peginterferon and ribavirin. METHODS: Adherence was evaluated prospectively
      among 196 African American and 205 white subjects enrolled in Virahep-C (Viral
      Resistance to Antiviral Therapy of Chronic Hepatitis C), a treatment study for
      genotype 1 HCV infection. Adherence to the prescribed dose was measured by 2
      methods: self-report questions administered during multiple clinic visits, using
      a touch screen computer; and recordings of bottle openings, using an electronic
      monitor placed inside the cap of prescription containers. Self-reported responses
      were compared with the electronic monitor data. Nonparametric tests were used to
      test the association between adherence measures at 4, 12, 24, 36, and 48 weeks of
      treatment. RESULTS: The estimated proportion of participants who were adherent
      prior to a given visit ranged from 85% to 97% (ribavirin) and 97% to 100%
      (peginterferon) by self report and from 69% to 90% (ribavirin) and 84% to 100%
      (peginterferon) by electronic monitors. For ribavirin, the percentage of cases in
      which the 2 measurement methods agreed varied from 68% to 90%; peginterferon
      agreement was from 84% to 100%. Overall, adherence was higher for peginterferon
      than for ribavirin but decreased over time for both medications. Self-reported
      adherence was usually higher than that assessed by electronic measures, and the
      level of discrepancy increased during the course of treatment. CONCLUSIONS:
      Adherence to peginterferon and ribavirin decreased gradually during therapy but
      remained relatively high. Simple self-reported measures can be used to screen for
      nonadherence to HCV drug therapy, but should be considered as overestimation of
      the actual amounts taken.

PMID- 17519300
TI  - Corticosteroid treatment of severe community-acquired pneumonia.
AB  - OBJECTIVE: To assess the evidence for adjunctive corticosteroids for severe
      community-acquired pneumonia (CAP). DATA SOURCES: MEDLINE (1966-February 2007)
      and EMBASE (1980-February 2007) were searched to identify English- and French
      language publications that evaluated the use of corticosteroids for CAP in
      adults. Major search terms included community-acquired pneumonia, intensive care
      unit, steroids, glucocorticoids, and adrenal cortex hormones. STUDY SELECTION AND
      DATA EXTRACTION: Clinical studies that evaluated the use of corticosteroids for
      CAP in adults were included. Clinical and surrogate markers of pneumonia were
      evaluated. DATA SYNTHESIS: Severe CAP is associated with an increase in pulmonary
      and circulatory cytokines such as interleukin-6 and tumor necrosis factor-alpha
      that may be associated with higher mortality. Corticosteroids suppress
      inflammatory reactions and prevent migration of inflammatory cells from the
      circulation to tissues by suppressing the synthesis of chemokines and cytokines.
      One observational comparative study and 2 randomized, controlled studies examined
      the effects of corticosteroid therapy at various doses on endpoints of pulmonary
      and systemic inflammation and clinical outcomes. One small observational pilot
      study revealed that methylprednisolone blunted some of the pulmonary and systemic
      markers of inflammation. One small, randomized, placebo-controlled study revealed
      that hydrocortisone had no significant effects on markers of pulmonary and
      systemic inflammation or clinical outcomes. Another small, randomized, placebo
      controlled preliminary study with methodological limitations revealed
      improvements in oxygenation, organ dysfunction score, and markers of inflammation
      favoring hydrocortisone over placebo. CONCLUSIONS: Given the lack of proven
      benefit on clinically meaningful endpoints and adverse events, corticosteroids
      cannot be recommended for adjunctive treatment of severe CAP.

PMID- 17519301
TI  - Acetaminophen and ibuprofen for prevention of adverse reactions associated with
      childhood immunization.
AB  - OBJECTIVE: To evaluate the literature examining prophylactic use of acetaminophen
      and ibuprofen for prevention of adverse reactions associated with childhood
      immunization. DATA SOURCES: Articles were identified via MEDLINE/PubMed/EMBASE
      (1966-March 2007) using the following key terms: vaccination, immunization,
      diphtheria-tetanus toxoids-whole pertussis (DTwP), diphtheria tetanus-toxoid,
      whole pertussis, diphtheria-tetanus toxoids-acellular pertussis (DTaP), acellular
      pertussis, Haemophilus influenzae type B, inactivated poliovirus, pneumococcal 7
      valent conjugate, measles, mumps, rubella, meningococcal C-conjugate, varicella
      zoster, hepatitis B, influenza, pneumococcal polysaccharide, adverse reactions,
      analgesics, antipyretics, acetaminophen, ibuprofen, infant, and child. STUDY
      SELECTION AND DATA EXTRACTION: No limitations were placed on article selection.
      DATA SYNTHESIS: Five articles examining the effects of prophylactic acetaminophen
      or ibuprofen for adverse effects associated with either DTaP or DTwP vaccine were
      retrieved. In one randomized controlled trial of children aged 4-6 years given
      DTaP, no effect of prophylactic acetaminophen 15 mg/kg/dose, up to 450 mg, or
      ibuprofen 10 mg/kg/dose, up to 300 mg, was found on the incidence of fever,
      redness, pain, swelling, or itching. In 3 randomized studies of DTwP, either
      acetaminophen 10-15 mg/kg/dose or ibuprofen 20 mg/kg/24 hours, given in 3 equal
      doses before or at the time of immunization and every 4-8 hours thereafter for 12
      or more hours, reduced fever, pain, fussiness, and local redness in infants 2-7
      months of age compared with placebo. Results were not duplicated in older
      infants/children. No studies investigated use of prophylactic acetaminophen or
      ibuprofen for any other vaccine. CONCLUSIONS: Use of prophylactic acetaminophen
      and ibuprofen may reduce the incidence of adverse reactions in young infants
      receiving DTwP vaccine; however, DTwP has been replaced with DTaP, and no
      benefits have been demonstrated for this vaccine when evaluated in children aged
      4-6 years, or with any other vaccine currently in use. Thus, neither drug can be
      recommended prophylactically to prevent vaccine-associated adverse reactions.
      Individuals at high risk for seizures may, however, warrant special
      consideration.

PMID- 17519302
TI  - Clinical experience with transdermal and orally administered opioids in
      palliative care patients--a retrospective study.
AB  - BACKGROUND: Transdermal fentanyl is a widely used opioid for the treatment of
      cancer pain. Simplicity of use and high patient compliance are the main
      advantages of this opioid. However, based on our clinical experience, transdermal
      fentanyl is often not efficacious in terminally ill palliative care patients. We
      thus retrospectively examined the pain management and need for opioid switching
      in cancer patients admitted to our palliative care unit. METHODS: Of 354 patients
      admitted to our palliative care unit from 2004 through 2005, 81 patients were pre
      treated with transdermal fentanyl. Demographic and cancer-related data
      (diagnosis, symptoms, pain score on a numeric rating scale (NRS)), analgesic dose
      at admission and discharge were compared. STATISTICS: mean +/- SD, ANOVA,
      Wilcoxon's test was used for inter-group comparisons, significance P < 0.05,
      adjusted for multiple testing. Pain scores are given in median (range). RESULTS:
      Mean transdermal fentanyl dose at admission was 81.0 +/- 55.8 microg/h. In 79
      patients transdermal fentanyl treatment was discontinued. In two patients,
      analgesic treatment according to WHO I provided sufficient pain relief. The other
      77 patients were switched to other opioids: 33 patients to oral morphine and 44
      to oral hydromorphone. In patients switched to morphine the dose at discharge
      (104.7 +/- 89.0 mg) was lower than at admission (165.5 mg morphine equivalence).
      In patients switched to hydromorphone the dose of 277.8 +/- 255.0 mg morphine
      equivalent was higher at discharge than at admission (218.2 +/- 131.4 mg morphine
      equivalence--considering an equianalgesic conversion ratio morphine:
      hydromorphone = 7.5: 1). Pain scores decreased significantly after opioid
      rotation (NRS at rest/on exertion: 4 (0-10)/7 (2-10) versus 1 (0-3)/2 (0-5); P <
      0.001). CONCLUSIONS: In the patient group switched to morphine, sufficient pain
      relief was achieved by lower equianalgesic morphine doses, compared with the
      doses at admission. In the patient group switched to hydromorphone, higher
      equianalgesic morphine doses were needed at discharge, considering an
      equianalgesic conversion ratio of morphine: hydromorphone = 7.5: 1. Patients with
      far advanced cancer often suffer from sweating and cachexia, which may have
      negative effects on the absorption of transdermal fentanyl. Opioid switching to
      oral morphine or hydromorphone was well tolerated and proved to be an efficacious
      option for cancer pain treatment.

PMID- 17519303
TI  - Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5'
      CpG island in endometriosis.
AB  - CONTEXT: Endometriosis is an estrogen-dependent disease. Steroidogenic factor-1
      (SF-1), a transcriptional factor essential for activation of multiple
      steroidogenic genes for estrogen biosynthesis, is undetectable in normal
      endometrial stromal cells and aberrantly expressed in endometriotic stromal
      cells. OBJECTIVE: The objective of the study was to unravel the mechanism for
      differential SF-1 expression in endometrial and endometriotic stromal cells.
      DESIGN: We identified a CpG island flanking the SF-1 promoter and exon I region
      and determined its methylation patterns in endometrial and endometriotic cells.
      SETTING: The study was conducted at Northwestern University. PATIENTS OR OTHER
      PARTICIPANTS: Eutopic endometrium from disease-free subjects (n = 8) and the
      walls of cystic endometriosis lesions of the ovaries (n = 8) were investigated.
      INTERVENTION(S): Stromal cells were isolated from these two types of tissues.
      MAIN OUTCOME MEASURE(S): Measures are mentioned in Results. RESULTS: SF-1 mRNA
      and protein levels in endometriotic stromal cells were significantly higher than
      those in endometrial stromal cells (P < 0.001). Bisulfite sequencing showed
      strikingly increased methylation in endometrial cells, compared with
      endometriotic cells (P < 0.001). Demethylation by 5-aza-2'-deoxycytidine
      increased SF-1 mRNA levels by up to 55.48-fold in endometrial cell (P < 0.05).
      Luciferase assays showed that the -85/+239 region bearing the CpG island
      regulated its activity (P < 0.01). Natural or in vitro methylation of this region
      strikingly reduced SF-1 promoter activity in both cell types (P < 0.01).
      Chromatin immunoprecipitation assay showed that methyl-CpG-binding domain protein
      2 binds to the SF-1 promoter in endometrial but not endometriotic cells.
      CONCLUSIONS: This is the first demonstration of methylation-dependent regulation
      of SF-1 in any mammalian tissue. These findings point to a new mechanism for
      targeting local estrogen biosynthesis in endometriosis.

PMID- 17519304
TI  - Ovarian androgen production in postmenopausal women.
AB  - CONTEXT: Several studies previously reported that the postmenopausal ovary
      produces androgens. However, these findings have recently been questioned in a
      group of women with adrenal insufficiency. OBJECTIVE: We sought to use
      contemporary assay methodologies to investigate whether the postmenopausal ovary
      is hormonally active and contributes to the circulating pool of androgens. DESIGN
      AND PATIENTS: Serum was collected from the ovarian veins of 13 postmenopausal
      women undergoing total abdominal hysterectomy and bilateral oophorectomy, with
      sufficient quantities obtained to allow for measurement of several hormones.
      Serum was also analyzed from peripheral blood collected preoperatively,
      intraoperatively, and postoperatively. SETTING: The study took place at the Los
      Angeles County Women's and Children's Hospital, University of Southern California
      Keck School of Medicine. MAIN OUTCOME MEASURES: Testosterone (T), androstenedione
      (A), dehydroepiandrosterone (DHEA), estrone (E1), and estradiol (E2) were
      measured by RIA with preceding organic solvent extraction and Celite column
      chromatography. RESULTS: Statistically significant gradients were seen between
      the ovarian venous and peripheral samples for T, A, DHEA, E1, and E2.
      Postoperative levels of T and E1, but not A, DHEA, or E2, were statistically
      significantly lower than preoperative levels. A gradient for T between the
      ovarian venous and peripheral blood was present in four of five women who were
      menopausal for more than 10 yr. CONCLUSIONS: The postmenopausal ovary is
      hormonally active, contributing significantly to the circulating pool of T.
      Furthermore, this contribution appears to persist in women as long as 10 yr
      beyond the menopause.

PMID- 17519305
TI  - Concomitant reduction of low-density lipoprotein-cholesterol and biomarkers of
      inflammation with low-dose simvastatin therapy in patients with type 1 diabetes.
AB  - CONTEXT: Cardiovascular disease is a major cause of mortality in type 1 diabetes
      (TIDM). TIDM is a proinflammatory state. Whereas there is consensus on lipid
      management in type 2 diabetes, there is a lack of data in type 1 diabetes. In
      addition to benefits on the lipid profile, statin therapy is antiinflammatory.
      OBJECTIVE: There are scant data on statin therapy in T1DM. Thus, we tested the
      effect of simvastatin, compared with placebo, on biomarkers of inflammation and
      monocyte function in TIDM patients. DESIGN: This was a double-blind, randomized,
      placebo-controlled study of T1DM patients, randomized to placebo or simvastatin,
      20 mg/d for 3 months. SETTING: The study was conducted at the University of
      California, Davis, Medical Center. PARTICIPANTS: Participants included patients
      with T1DM. METHODS AND RESULTS: Analytes measured at baseline and 3 months
      included liver function tests, creatinine, hemoglobin AIC, high-sensitivity C
      reactive protein, soluble CD40 ligand, monocyte O(2)(-), cytokines, nuclear
      factor-kappaB. Simvastatin therapy resulted in significant reduction in low
      density lipoprotein and non-high-density lipoprotein cholesterol, high
      sensitivity C-reactive protein (18% reduction, P < 0.001) and soluble CD40 ligand
      (22% reduction, P < 0.05), compared with placebo. Simvastatin therapy
      significantly inhibited lipopolysaccharide-activated monocyte release of O(2)(-)
      (P < 0.0005), IL-8 (P < 0.03), and TNF (P < 0.02). Simvastatin therapy
      significantly inhibited monocyte IL-6 release, compared with baseline (P = 0.02).
      Simvastatin therapy also significantly reduced monocytic nuclear factor-kappaB
      p65 activity, compared with placebo (P < 0.01). CONCLUSIONS: This study
      demonstrates that simvastatin (20 mg/d) is safe in T1DM patients and has
      concomitant benefits on the lipid profile and biomarkers of inflammation. These
      novel findings could have implications for developing policy guidelines for
      statin therapy in forestalling vascular complications in young T1DM.

PMID- 17519306
TI  - Hormonal and nutritional effects on cardiovascular risk markers in young women.
AB  - CONTEXT: Cardiovascular (CV) risk markers, including high-sensitivity C-reactive
      protein (hsCRP), are increasingly important in predicting cardiac events. A
      favorable CV risk profile might be expected in anorexia nervosa (AN) due to low
      body weight and dietary fat intake. However, women with AN have decreased IGF-I
      levels reflecting decreased GH action, and IGF-I deficiency is associated with
      elevated hsCRP. Moreover, oral estrogens, known to increase hsCRP in other
      populations, are commonly prescribed in AN. To date, hsCRP levels and their
      physiological determinants have not been reported in women with AN. OBJECTIVE: We
      examined the relationship between CV risk markers, undernutrition, IGF-I, and
      oral estrogens, specifically hypothesizing that in the setting of undernutrition,
      AN would be associated with low hsCRP despite low IGF-I levels and that those
      women taking oral contraceptive pills (OCPs) would have higher hsCRP and lower
      IGF-I levels. DESIGN AND SETTING: We conducted a cross-sectional study at a
      clinical research center. STUDY PARTICIPANTS: Subjects included 181 women: 140
      women with AN [85 not receiving OCPs (AN-E) and 55 receiving OCPs (AN+E)] and 41
      healthy controls [28 not receiving OCPs (HC-E) and 13 receiving OCPs (HC+E)].
      MAIN OUTCOME MEASURES: We assessed hsCRP, IL-6, IGF-I, low-density lipoprotein
      (LDL), and high-density lipoprotein (HDL). RESULTS: Despite low weight, more than
      20% of AN+E had high-risk hsCRP levels. AN+E had higher hsCRP than AN-E. AN-E had
      lower mean hsCRP levels than healthy controls (HC+E and HC-E). IL-6 levels were
      higher in AN+E with elevated hsCRP (>3 mg/liter) than in AN+E with normal hsCRP
      levels. IGF-I was inversely associated with hsCRP in healthy women, suggesting a
      protective effect of GH on CV risk. However, this was not seen in AN. Few
      patients in any group had high-risk LDL or HDL levels. CONCLUSIONS: Although
      hsCRP levels are lower in AN than healthy controls, OCP use puts such women at a
      greater than 20% chance of having hsCRP in the high-CV-risk (>3 mg/liter)
      category. The elevated mean IL-6 in women with AN and high-risk hsCRP levels
      suggests that increased systemic inflammation may underlie the hsCRP elevation in
      these patients. Although OCP use in AN was associated with slightly lower mean
      LDL and higher mean HDL, means were within the normal range, and few patients in
      any group had high-risk LDL or HDL levels. IGF-I levels appear to be important
      determinants of hsCRP in healthy young women. In contrast, IGF-I does not appear
      to mediate hsCRP levels in AN.

PMID- 17519307
TI  - Meal-stimulated glucagon release is associated with postprandial blood glucose
      level and does not interfere with glycemic control in children and adolescents
      with new-onset type 1 diabetes.
AB  - CONTEXT: The role of glucagon in hyperglycemia in type 1 diabetes is unresolved,
      and in vitro studies suggest that increasing blood glucose might stimulate
      glucagon secretion. OBJECTIVE: Our objective was to investigate the relationship
      between postprandial glucose and glucagon level during the first 12 months after
      diagnosis of childhood type 1 diabetes. DESIGN: We conducted a prospective,
      noninterventional, 12-month follow-up study conducted in 22 centers in 18
      countries. PATIENTS: Patients included 257 children and adolescents less than 16
      yr old with newly diagnosed type 1 diabetes; 204 completed the 12-month follow
      up. SETTING: The study was conducted at pediatric outpatient clinics. MAIN
      OUTCOME MEASURES: We assessed residual beta-cell function (C-peptide),
      glycosylated hemoglobin (HbA(1c)), blood glucose, glucagon, and glucagon-like
      peptide-1 (GLP-1) release in response to a 90-min meal stimulation (Boost) at 1,
      6, and 12 months after diagnosis. RESULTS: Compound symmetric repeated
      measurements models including all three visits showed that postprandial glucagon
      increased by 17% during follow-up (P = 0.001). Glucagon levels were highly
      associated with postprandial blood glucose levels because a 10 mmol/liter
      increase in blood glucose corresponded to a 20% increase in glucagon release (P =
      0.0003). Glucagon levels were also associated with GLP-1 release because a 10%
      increase in GLP-1 corresponded to a 2% increase in glucagon release (P = 0.0003).
      Glucagon levels were not associated (coefficient -0.21, P = 0.07) with HbA(1c),
      adjusted for insulin dose. Immunohistochemical staining confirmed the presence of
      Kir6.2/SUR1 in human alpha-cells. CONCLUSION: Our study supports the recent in
      vitro data showing a stimulation of glucagon secretion by high glucose levels.
      Postprandial glucagon levels were not associated with HbA(1c), adjusted for
      insulin dose, during the first year after onset of childhood type 1 diabetes.

PMID- 17519308
TI  - Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia.
AB  - CONTEXT: Germline mutations in the MEN1 gene predispose to multiple endocrine
      neoplasia type 1 (MEN1) syndrome, but in up to 20-25% of clinical MEN1 cases, no
      MEN1 mutations can be found. Recently, a germline mutation in the CDKN1B gene,
      encoding p27(Kip1), was reported in one suspected MEN1 family with two
      acromegalic patients. OBJECTIVE: Our objective was to evaluate the role of
      CDKN1B/p27(Kip1) in human tumor predisposition in patients clinically suspected
      of MEN1 but testing negative for MEN1 germline mutation as well as in familial
      and sporadic acromegaly/pituitary adenoma patients. DESIGN: Genomic DNA was
      analyzed for germline mutations in the CDKN1B/p27(Kip1) gene by PCR amplification
      and direct sequencing. SETTING: The study was conducted at nonprofit academic
      research and medical centers. PATIENTS: Thirty-six Dutch and one German suspected
      MEN1 patient, who previously tested negative for germline MEN1 gene mutations,
      were analyzed. In addition, 19 familial and 50 sporadic acromegaly/pituitary
      adenoma patients from Europe and the United States were included in the study.
      MAIN OUTCOME MEASURES: We analyzed germline CDKN1B/p27(Kip1) mutations in
      individuals with pituitary adenoma and MEN1-like features. RESULTS: A
      heterozygous 19-bp duplication (c.59_77dup19) leading to a truncated protein
      product was identified in one Dutch patient with suspected MEN1 phenotype,
      pituitary adenoma, carcinoid tumor, and hyperparathyroidism (one of 36, 2.8%). No
      mutations were detected in either familial or sporadic acromegaly/pituitary
      adenoma patients. CONCLUSIONS: Our results support the previous finding that
      germline CDKN1B/p27(Kip1) mutations predispose to a human MEN1-like condition.
      However, such mutations appear uncommon in suspected MEN1 cases and rare or
      nonexistent in familial or sporadic acromegaly/pituitary adenoma patients.

PMID- 17519310
TI  - Evaluation of the biological activity of a growth hormone (GH) mutant (R77C) and
      its impact on GH responsiveness and stature.
AB  - CONTEXT AND OBJECTIVE: A single missense mutation in the GH-1 gene converting
      codon 77 from arginine (R) to cysteine (C) yields a mutant GH-R77C peptide, which
      was described as natural GH antagonist. DESIGN, SETTING, AND PATIENTS:
      Heterozygosity for GH-R77C/wt-GH was identified in a Syrian family. The index
      patient, a boy, was referred for assessment of his short stature (-2.5 SD score)
      and partial GH insensitivity was diagnosed. His mother and grandfather were also
      carrying the same mutation and showed partial GH insensitivity with modest short
      stature. INTERVENTIONS AND RESULTS: Functional characterization of the GH-R77C
      was performed through studies of GH receptor binding and activation of Janus
      kinase 2/Stat5 pathway. No differences in the binding affinity and bioactivity
      between wt-GH and GH-R77C were found. Similarly, cell viability and proliferation
      after expression of both GH peptides in AtT-20 cells were identical. Quantitative
      confocal microscopy analysis revealed no significant difference in the extent of
      subcellular colocalization between wt-GH and GH-R77C with endoplasmic reticulum,
      Golgi, or secretory vesicles. Furthermore studies demonstrated a reduced
      capability of GH-R77C to induce GHR/GHBP gene transcription rate when compared
      with wt-GH. CONCLUSION: Reduced GH receptor/GH-binding protein expression might
      be a possible cause for the partial GH insensitivity with delay in growth and
      pubertal development found in our patients. In addition, this group of patients
      deserves further attention because they could represent a distinct clinical
      entity underlining that an altered GH peptide may also have a direct impact on
      GHR/GHBP gene expression causing partial GH insensitivity.

PMID- 17519311
TI  - Determinants of early atherosclerosis in obese children and adolescents.
AB  - CONTEXT: Obesity in childhood is associated with an increased mortality due to
      cardiovascular (CV) diseases in adulthood, independent of adult weight. Recent
      studies in children indicate that the atherosclerosis process starts at an early
      age and is linked to obesity. OBJECTIVE: The aim of the study was to investigate
      determinants of increased carotid intima-media thickness (IMT), an early marker
      of atherosclerosis, in obese children. DESIGN: A total of 104 obese children
      [age, 12.7 +/- 0.2 yr; body mass index (BMI)-z-score, 2.8 +/- 0.7] underwent an
      oral glucose tolerance test. Fasting levels of glucose, insulin, C-reactive
      protein and adhesion molecules (sICAM, sVCAM, sE-selectin), lipid profile,
      adiponectin, and resistin were determined. IMT was measured by ultrasound.
      Insulin resistance was estimated by the homeostatic model assessment index.
      Baseline measurements of blood parameters were obtained from 93 nonobese children
      (age, 13.0 +/- 0.2 yr; BMI-z-score, -0.2 +/- 0.9), and IMT was measured in 23
      other control children with similar characteristics. RESULTS: Univariate analysis
      showed a significant positive correlation between IMT and relative BMI, the
      degree of systolic hypertension, fasting insulin levels, homeostatic model
      assessment-R index, and resistin concentrations, whereas an inverse correlation
      with adiponectin levels was found. No correlation was obtained between IMT and
      classical CV risk factors such as positive familial history of type 2 diabetes or
      precocious CV disease, visceral obesity, or the lipid profile. C-reactive protein
      and adhesion molecule levels were not associated with IMT in our obese
      population. When controlled for sex, Tanner stage, and relative BMI, only
      adiponectin levels remained an independent determinant of IMT. CONCLUSION:
      Adiponectin more than conventional CV risk factors and inflammation status may be
      related to early atherosclerosis in obese children.

PMID- 17519312
TI  - Insulin sensitivity after metformin suspension in normal-weight women with
      polycystic ovary syndrome.
AB  - CONTEXT: To date, the metabolic effects of the long-term metformin administration
      in anovulatory patients with polycystic ovary syndrome (PCOS) are known, whereas
      few data are available on the effects of its suspension. OBJECTIVE: The objective
      of the study was to evaluate the effects of metformin suspension on insulin
      sensitivity in PCOS patients. DESIGN: This was a prospective, randomized, placebo
      controlled study. SETTING: The study was conducted at the University "Magna
      Graecia" of Catanzaro, Italy. PATIENTS: Patients included 30 normal-weight
      anovulatory PCOS women and 10 age- and body mass index-matched healthy controls.
      INTERVENTION: PCOS patients were randomized to receive 1700 mg daily metformin
      (metformin group) or placebo tables (placebo group) for 12 months, whereas no
      treatment was administered in healthy women (control group). MAIN OUTCOME
      MEASURES: Clinical, endocrine, and metabolic profile and clamp insulin
      sensitivity index were evaluated at study entry and after 6, 12, 18, and 24
      months. RESULTS: At baseline, the clamp insulin sensitivity index resulted
      significantly different (P < 0.05) in PCOS patients in comparison with healthy
      controls, without difference between metformin and placebo groups. During
      treatment, the clamp insulin sensitivity index was significantly improved (P <
      0.05) in the metformin group in comparison with baseline and placebo group,
      without significant differences between the 6- and 12-month assessments. At 6 and
      12 months after treatment suspension, in the metformin group, insulin sensitivity
      index significantly (P < 0.05) worsened in comparison with that observed at
      baseline and during treatment and with that observed in the placebo and control
      groups. CONCLUSION: In normal-weight anovulatory PCOS patients, long-term
      metformin administration exerts beneficial effects on peripheral insulin
      sensitivity. Furthermore, this effect disappears at treatment suspension.

PMID- 17519313
TI  - Growth hormone treatment in adolescent males with idiopathic short stature:
      changes in body composition, protein, fat, and glucose metabolism.
AB  - CONTEXT: Cross-sectional observations show an inverse relationship between
      pubertal increase in GH and insulin sensitivity, suggesting that pubertal insulin
      resistance may be mediated by GH. OBJECTIVE: Our objective was to assess
      longitudinally the effects of short-term GH supplementation in adolescent males
      with non-GH-deficient idiopathic short stature (ISS) on body composition,
      substrate metabolism, and insulin sensitivity. Children with ISS were studied to
      simulate the pubertal increase in GH secretion. PARTICIPANTS AND SETTING: Eight
      males with ISS (10.8-16.5 yr) were recruited from pediatric endocrinology clinics
      at an academic medical center. STUDY DESIGN: Participants were evaluated in the
      General Clinical Research Center before and after 4 months of GH supplementation
      (0.3 mg/kg.wk). Body composition was assessed with dual-energy x-ray
      absorptiometry. Whole-body glucose, protein, and fat turnover were measured using
      stable isotopes. In vivo insulin action was assessed during a 3-h
      hyperinsulinemic (40 mU/m(2).min) euglycemic clamp. RESULTS: GH supplementation
      led to 1) increase in hepatic glucose production and fasting insulin levels, 2)
      increase in lean body mass and decrease in fat mass, and 3) improvement in
      cardiovascular lipid risk profile. Plasma IGF-I levels correlated positively with
      insulin levels. CONCLUSIONS: Four months of GH supplementation in adolescent
      males with ISS is associated with significant body composition changes and
      hepatic insulin resistance.

PMID- 17519314
TI  - Serum sex hormone-binding globulin levels in healthy children and girls with
      precocious puberty before and during gonadotropin-releasing hormone agonist
      treatment.
AB  - CONTEXT: The regulation of SHBG is complex and influenced by sex steroids and
      insulin. OBJECTIVE: Our objective was to describe serum levels and evaluate
      determinants of SHBG levels in healthy children and in girls with central
      precocious puberty (CPP) before and during GnRH analog (GnRHa) treatment. DESIGN:
      We conducted a cross-sectional study on healthy subjects and a 2-yr longitudinal
      study in girls with CPP. SETTING: The study took place at a tertiary referral
      center for pediatric endocrinology. PARTICIPANTS/PATIENTS: A total of 903 healthy
      schoolchildren served as healthy subjects, and 25 girls with precocious/early
      puberty participated. INTERVENTIONS: Girls with CPP were treated with the long
      acting GnRHa triptorelin. RESULTS: SHBG levels declined with increasing age in
      both sexes until adulthood. In healthy children, SHBG was significantly
      negatively correlated with testosterone, estradiol, dehydroepiandrosterone
      sulfate, and body mass index (BMI) in boys (total model R(2) = 0.71) but only
      with dehydroepiandrosterone sulfate and BMI in girls (total model R(2) = 0.26).
      Body fat percentage was significantly negatively correlated with SHBG levels (P <
      0.001) in both boys (R(2) = 0.18) and girls (R(2) = 0.23). Girls with CPP had
      significantly lower pretreatment SHBG levels compared with age-matched controls
      [SHBG sd score, -1.29 (-4.48; 0.01)], which declined even further during GnRHa
      treatment [-2.75 (-5.9; 0.53); P < 0.001]. Even after adjustment for BMI and
      pubertal stage, girls with CPP had lower SHBG levels (P < 0.001) compared with
      healthy controls. CONCLUSIONS: SHBG levels were strongly dependent on body
      composition and sex steroid levels in children with normal and precocious
      puberty. Studies on insulin sensitivity and SHBG in puberty are needed to better
      understand the interaction between body composition and gonadal maturation.

PMID- 17519315
TI  - Sleep loss alters basal metabolic hormone secretion and modulates the dynamic
      counterregulatory response to hypoglycemia.
AB  - CONTEXT: Sleep loss has immediate effects on metabolic function that in the long
      run may contribute to the development of obesity and type 2 diabetes. OBJECTIVE:
      Our objective was to explore the neuroendocrine mechanisms mediating the acute
      effects of sleep deprivation on blood glucose regulation under basal and
      hypoglycemic conditions. METHODS: In a randomized, crossover study in 10 healthy
      young men, plasma concentrations of relevant hormones were examined during basal
      rest, a subsequent stepwise hypoglycemic clamp after one night of total sleep
      deprivation (SD) and one night of regular sleep. RESULTS: Basal glucagon
      concentrations were decreased (P = 0.022) and C-peptide levels were slightly
      reduced after SD (P = 0.085), compared with regular sleep. During hypoglycemia
      after SD, the glucagon increase relative to baseline was enhanced (P = 0.034) and
      the relative decrease in C-peptide was reduced (P = 0.013). Also, the relative
      increase in norepinephrine was reduced (P = 0.031). SD did not affect
      epinephrine, ACTH, cortisol, lactate, beta-hydroxybutyrate, or nonesterified
      fatty acids during hypoglycemia, but overall, plasma nonesterified fatty acid
      levels were reduced after SD (P = 0.009). SD markedly increased rated hunger
      during basal rest (P < 0.008), resulting in a dampened relative increase during
      hypoglycemia (P < 0.009). Unexpectedly, despite distinct alterations in basal
      secretory activity, the absolute amplitude of hormonal counterregulation and
      hunger responses to hypoglycemia was not affected by SD. CONCLUSION: Short-term
      SD distinctly alters hormonal glucose regulation, affecting especially pancreatic
      islet secretion, and also increases hunger. Immediate perturbations in the
      dynamic regulation of energy metabolism caused by acute sleep curtailment may
      contribute to the association between chronic sleep loss and metabolic disorders.

PMID- 17519316
TI  - Altered activity of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in skeletal
      muscle confers metabolic protection in subjects with type 2 diabetes.
AB  - CONTEXT: There is little information regarding the regulation of 11beta
      hydroxysteroid dehydrogenase (11beta-HSD) enzymes in skeletal muscle in the
      setting of type 2 diabetes. OBJECTIVE: Our objective was to investigate whether
      there is differential mRNA expression and enzyme activity of 11beta-HSD1 and
      11beta-HSD2 in the skeletal muscle of diabetic subjects compared with controls at
      baseline and in response to dexamethasone. DESIGN: Participants underwent muscle
      biopsy of vastus lateralis at baseline and after dexamethasone. SETTING: The
      study took place at a university teaching hospital. PARTICIPANTS: Twelve subjects
      with type 2 diabetes and 12 age- and sex-matched controls participated.
      INTERVENTION: Subjects were given oral dexamethasone, 4 mg/d for 4 d. MAIN
      OUTCOME MEASURES: We assessed 11beta-HSD1, 11beta-HSD2, and H6PDH mRNA levels by
      quantitative RT-PCR and enzyme activity by percent conversion of [(3)H]cortisone
      and [(3)H]cortisol, respectively. RESULTS: At baseline, mRNA levels were similar
      in diabetic and control subjects for 11beta-HSD1, 11beta-HSD2, and H6PDH. 11beta
      HSD1 activity was reduced in diabetic subjects (percent conversion of
      [(3)H]cortisone to [(3)H]cortisol was 11.4 +/- 2.5% vs. 18.5 +/- 2.2%; P =
      0.041), and 11beta-HSD2 enzyme activity was higher in diabetic subjects (percent
      conversion of [(3)H]cortisone to [(3)H]cortisol was 17.2 +/- 2.6% vs. 9.2 +/-
      1.3%; P = 0.012). After dexamethasone, 11beta-HSD1 mRNA increased in both groups
      (P < 0.001), whereas 11beta-HSD2 mRNA decreased (P = 0.002). 11beta-HSD1 activity
      increased in diabetic subjects (P = 0.021) but not in controls, whereas 11beta
      HSD2 activity did not change in either group. At baseline, there was a
      significant negative correlation between 11beta-HSD1 and 11beta-HSD2 enzyme
      activity (r = -0.463; P = 0.026). CONCLUSIONS: The activities of skeletal muscle
      11beta-HSD1 and 11beta-HSD2 are altered in diabetes, which together may reduce
      intracellular cortisol generation, potentially conferring metabolic protection.

PMID- 17519317
TI  - Effects of diet-induced moderate weight reduction on intrahepatic and
      intramyocellular triglycerides and glucose metabolism in obese subjects.
AB  - CONTEXT: Although moderate weight reduction is recommended as primary therapy of
      metabolic syndrome, little information is known regarding metabolic changes
      associated with moderate weight reduction in nondiabetic obese subjects.
      OBJECTIVE: The aim of this study was to determine the effects of a moderate
      weight reduction program on intracellular lipid and glucose metabolism in muscle
      and liver. PARTICIPANTS: Data for 13 nondiabetic obese subjects were evaluated.
      INTERVENTION: Subjects were put on a 3-month mildly hypocaloric diet therapy
      (approximately 35 kcal/kg of ideal body weight). MAIN OUTCOME MEASURES:
      Intrahepatic lipid (IHL) and intramyocellular lipid were measured by using (1)H
      magnetic resonance spectroscopy. Peripheral insulin sensitivity and splanchnic
      glucose uptake were evaluated by euglycemic-hyperinsulinemic clamp with oral
      glucose load. RESULTS: Diet therapy for 3 months resulted in 6% reduction in body
      weight (from 99.9 +/- 7.3 to 93.8 +/- 6.6 kg, P < 0.0001). This change was
      accompanied by reduction of plasma glucose and insulin excursions during 75-g
      oral glucose tolerance tests, decrease in diastolic blood pressure, glycated
      hemoglobin, serum low-density lipoprotein cholesterol, and triglyceride. These
      changes were also accompanied by a decrease in IHL (from 12.9 to 8.2%, P < 0.01)
      and increase in splanchnic glucose uptake (from 13.5 to 35.0%, P < 0.03). On the
      other hand, the diet program did not affect intramyocellular lipid or glucose
      infusion rate during euglycemic hyperinsulinemic clamp. CONCLUSIONS: Our results
      suggest that moderate weight reduction in obese subjects decreased IHL and
      augmented splanchnic glucose uptake. This mechanism is at least in part involved
      in improvement of glucose metabolism by moderate weight reduction in obese
      subjects.

PMID- 17519318
TI  - Infantile hypophosphatasia: transplantation therapy trial using bone fragments
      and cultured osteoblasts.
AB  - BACKGROUND: Hypophosphatasia (HPP) is a rare, heritable, metabolic bone disease
      due to deficient activity of the tissue-nonspecific isoenzyme of alkaline
      phosphatase. The infantile form features severe rickets often causing death in
      the first year of life from respiratory complications. There is no established
      medical treatment. In 1997, an 8-month-old girl with worsening and life
      threatening infantile HPP improved considerably after marrow cell
      transplantation. OBJECTIVE: Our aim was to better understand and to advance these
      encouraging transplantation results. DESIGN: In 1999, based on emerging mouse
      transplantation models involving implanted donor bone fragments as well as
      osteoblast-like cells cultured from bone, we treated a 9-month-old girl suffering
      a similar course of infantile HPP. RESULTS: Four months later, radiographs
      demonstrated improved skeletal mineralization. Twenty months later, PCR analysis
      of adherent cells cultured from recipient bone suggested the presence of small
      amounts of paternal (donor) DNA despite the absence of hematopoietic engraftment.
      This patient, now 8 yr old (7 yr after transplantation), is active and growing,
      and has the clinical phenotype of the more mild, childhood form of HPP.
      CONCLUSIONS: Cumulative experience suggests that, after immune tolerance, donor
      bone fragments and marrow may provide precursor cells for distribution and
      engraftment in the skeletal microenvironment in HPP patients to form tissue
      nonspecific isoenzyme of alkaline phosphatase-replete osteoblasts that can
      improve mineralization.

PMID- 17519319
TI  - Water drinking induces thermogenesis through osmosensitive mechanisms.
AB  - CONTEXT: Recently, we showed that drinking 500 ml water induces thermogenesis in
      normal-weight men and women. OBJECTIVE: We now repeated these studies in a
      randomized, controlled, crossover trial in overweight or obese otherwise healthy
      subjects (eight men and eight women), comparing also the effects of 500 ml
      isoosmotic saline or 50 ml water. RESULTS: Only 500 ml water increased energy
      expenditure by 24% over the course of 60 min after ingestion, whereas isoosmotic
      saline and 50 ml water had no effect. Heart rate and blood pressure did not
      change in these young, healthy subjects. CONCLUSIONS: Our data exclude volume
      related effects or gastric distension as the mediator of the thermogenic response
      to water drinking. Instead, we hypothesize the existence of a portal
      osmoreceptor, most likely an ion channel.

PMID- 17519320
TI  - Prolonged activation EEG differentiates dementia with and without delirium in
      frail elderly patients.
AB  - OBJECTIVE: Delirium in the elderly results in increased morbidity, mortality and
      functional decline. Delirium is underdiagnosed, particularly in dementia. To
      increase diagnostic accuracy, we investigated whether maintenance of activation
      assessed by EEG discriminates delirium in association with dementia (D+D) from
      dementia without delirium (DP) and cognitively unimpaired elderly subjects (CU).
      METHOD: Routine and quantitative EEG (rEEG/qEEG) with additional prolonged
      activation (3 min eyes open period) were evaluated in hospitalised elderly
      patients with acute geriatric disease. Patients were assigned post hoc to three
      comparable groups (D+D/DP/CU) by expert consensus based on DSM-IV criteria.
      Dementia diagnosis was confirmed using cognitive and functional tests and
      caregiver rating (IQCODE, Informed Questionnaire of Cognitive Decline in the
      Elderly). RESULTS: While rEEG at rest showed low accuracy for a diagnosis of
      delirium, qEEG in DP and CU revealed a specific activation pattern of high
      significance found to be absent in the D+D group. Stepwise logistic regression
      confirmed that differentiation of D+D from DP was best resolved using activated
      upper alpha and delta power density which, compared with rEEG, enabled an 11%
      increase in diagnostic correctness to 83%, resulting in 67% sensitivity and 91%
      specificity. Among frail CU and D+D subjects, almost 90% were correctly
      classified. CONCLUSION: Dementia associated with delirium can be discriminated
      reliably from dementia alone in a meaningful clinical setting. Thus EEG
      evaluation in chronic encephalopathy should be optimised by a simple activation
      task and spectral analysis, particularly in the elderly with dementia.

PMID- 17519321
TI  - Cognitive function in patients with late stage amyotrophic lateral sclerosis.
AB  - BACKGROUND: Subtle cognitive deficits have been found in a substantial percentage
      of patients with early stage amyotrophic lateral sclerosis (ALS). Cognitive
      function in later stages of the disease remain to be investigated because the
      neuropsychological tests that are usually employed, such as written or verbal
      fluency tests, cannot be performed by those patients because of motor or speech
      impairment, or both. METHODS: In the present study, 11 patients with late stage
      ALS who were severely physically impaired and matched controls underwent a
      neuropsychological test battery to explore their cognitive function with respect
      to disease related functional status. Testing was restricted to tasks that used a
      binary (yes/no) signal and did not require verbalisation or measures of reaction
      time to index performance. RESULTS: Although some patients displayed deficits in
      aspects of executive function, learning and memory, overall test results
      indicated normal cognitive function. A statistically highly significant negative
      correlation was found between the performance on two learning and memory tasks
      and the functional status of the patients. CONCLUSION: The results of this study
      indicate a superior performance on learning and memory tasks of patients whose
      disease had further progressed. This may have important implications for our view
      on cognitive function in relation to the course of the disease.

PMID- 17519322
TI  - Repetitive asystole in right insular haemorrhage.

PMID- 17519323
TI  - Functional imaging of the cerebral olfactory system in patients with Parkinson's
      disease.
AB  - BACKGROUND: Olfactory dysfunction is a frequent non-motor symptom in Parkinson's
      disease (PD) and is considered to be an early manifestation of the disease.
      OBJECTIVE: To establish the cortical basis of olfactory function in patients with
      PD. METHOD: Functional magnetic resonance imaging (fMRI) was used to investigate
      brain activity related to olfactory processing in patients with hyposmic PD at
      mild to moderate stages of the disease (n = 12, median Hoehn and Yahr stage 2.0)
      and in healthy, age-matched controls (n = 16) while passively perceiving a
      positively valenced (rose-like) odorant. RESULTS: In both patients with PD and
      healthy controls, olfactory stimulation activated brain regions relevant for
      olfactory processing (ie the amygdaloid complex, lateral orbitofrontal cortex,
      striatum, thalamus, midbrain and the hippocampal formation). In controls, a
      bilateral activation of the amygdala and hippocampus was observed, whereas
      patients with PD involved these structures in the left hemisphere only. Group
      comparison showed that regions of higher activation in patients with PD were
      located bilaterally in the inferior frontal gyrus (BA 44/45) and anterior
      cingulate gyrus (BA 24/32), and the left dorsal and right ventral striatum.
      CONCLUSIONS: In patients with PD, results obtained under the specific conditions
      used suggest that neuronal activity in the amygdala and hippocampus is reduced.
      Assuming an impact on olfactory-related regions early in PD, our findings support
      the idea that selective impairment of these brain regions contributes to
      olfactory dysfunction. Furthermore, neuronal activity in components of the
      dopaminergic, cortico-striatal loops appears to be upregulated, indicating that
      compensatory processes are involved. This mechanism has not yet been demonstrated
      during olfactory processing in PD.

PMID- 17519324
TI  - FSH stimulates the expression of the ADAMTS-16 protease in mature human ovarian
      follicles.
AB  - We report the characterization of full-length human ADAMTS (a disintegrin and
      metalloproteinase with thrombospondin motifs)-16, a novel member of the
      disintegrin and metalloproteinase with thrombospondin motifs (hence ADAMTS)
      family. ADAMTS-16 is highly expressed both in the kidney and in the ovary, where
      it is predominantly expressed in the parietal granulosa cells of pre-ovulatory
      follicles but only slightly expressed in cells of the cumulus oophorus. In fully
      differentiated luteinizing granulosa cells, follicle-stimulating hormone and
      forskolin induces expression of ADAMTS-16, suggesting that it is regulated via
      the cAMP pathway. Luteinizing hormone had a minor effect on the expression of
      ADAMTS-16. ADAMTS-16 is capable of cleaving alpha2-macroglobulin (MG), a common
      substrate for proteases, which is present at high concentrations in the
      follicular fluid of ovarian follicles. These studies provide the first evidence
      that ADAMTS-16 is an active protease and suggest a physiological role of ADAMTS
      16 in ovarian follicles, at least during the pre-ovulatory phase.

PMID- 17519325
TI  - The high-pressure dimension in earth and planetary science.

PMID- 17519326
TI  - Profile of Daniel L. Hartl.

PMID- 17519327
TI  - An early infructescence Hyrcantha decussata (comb. nov.) from the Yixian
      Formation in northeastern China.
AB  - The continuing study of early angiosperms from the Yixian Formation
      (approximately 125 Ma) of northeastern China has yielded a second early
      angiosperm genus. This report is a detailed account of this early flowering plant
      and recognizes earlier reports of similar fossils from Russia and China. Entire
      plants, including roots, stems, and branches terminating in fruits are presented
      and reconstructed. Evidence for a possible aquatic nature of this plant is
      presented. The relationship of Hyrcantha ("Sinocarpus") to the eudicots is
      discussed. The presence of this second early angiosperm genus, now known as a
      whole plant, is important in the discussion of its systematics and the ecology of
      the earliest angiosperms.

PMID- 17519328
TI  - Sildenafil accelerates reentrainment of circadian rhythms after advancing light
      schedules.
AB  - Mammalian circadian rhythms are generated by a master clock located in the
      suprachiasmatic nuclei and entrained by light-activated signaling pathways. In
      hamsters, the mechanism responsible for light-induced phase advances involves the
      activation of guanylyl cyclase, cGMP and its related kinase (PKG). It is not
      completely known whether interference with this pathway affects entrainment of
      the clock, including adaptation to changing light schedules. Here we report that
      cGMP-specific phosphodiesterase 5 is present in the hamster suprachiasmatic
      nuclei, and administration of the inhibitor sildenafil (3.5 mg/kg, i.p.) enhances
      circadian responses to light and decreases the amount of time necessary for
      reentrainment after phase advances of the light-dark cycle. These results suggest
      that sildenafil may be useful for treatment of circadian adaptation to
      environmental changes, including transmeridian eastbound flight schedules.

PMID- 17519329
TI  - GPR37 associates with the dopamine transporter to modulate dopamine uptake and
      behavioral responses to dopaminergic drugs.
AB  - The orphan G protein-coupled receptor 37 (GPR37) is a substrate of parkin; its
      insoluble aggregates accumulate in brain samples of Parkinson's disease patients.
      We report here that GPR37 interacts with the dopamine transporter (DAT) and
      modulates DAT activity. GPR37 and DAT were found colocalized in mouse striatal
      presynaptic membranes and in transfected cells and their interaction was
      confirmed by coimmunoprecipitation assays. Gpr37-null mutant mice showed enhanced
      DAT-mediated dopamine uptake in striatal membrane samples, with a significant
      increase in the number of plasma membrane DAT molecules. The null mutant mice
      also exhibited a decrease in cocaine-induced locomotor activity and in catalepsy
      induced by dopamine receptor antagonists. These results reveal the specific role
      of GPR37, a putative peptidergic G protein-coupled receptor, in modulating the
      functional expression of DAT and the behavioral responses to dopaminergic drugs.

PMID- 17519330
TI  - Apres le deluge: microbial landscape of New Orleans after the hurricanes.

PMID- 17519331
TI  - An RNA-making reactor for the origin of life.

PMID- 17519332
TI  - Canonical Wnt signaling functions in second heart field to promote right
      ventricular growth.
AB  - The second heart field (SHF), progenitor cells that are initially sequestered
      outside the heart, migrates into the heart and gives rise to endocardium,
      myocardium, and smooth muscle. Because of its distinct developmental history, the
      SHF is likely subjected to different signals from that of the first heart field.
      Previous experiments revealed that canonical Wnt signaling negatively regulated
      first heart field specification. We inactivated the obligate canonical Wnt
      effector beta-catenin using a beta-catenin conditional null allele and the Mef2c
      AHF cre driver that directs cre activity specifically in SHF. We also expressed a
      stabilized form of beta-catenin to model continuous Wnt signaling in SHF. Our
      data indicate that Wnt signaling acts in a positive fashion to promote right
      ventricular and interventricular myocardial expansion. Cyclin D2 and Tgfbeta2
      expression was drastically reduced in beta-catenin loss-of-function mutants,
      indicating that Wnt signaling is required for patterning and expansion of SHF
      derivatives. Our findings reveal that Wnt signaling plays a major positive role
      in promoting growth and diversification of SHF precursors into right ventricular
      and interventricular myocardium.

PMID- 17519333
TI  - Beta-catenin directly regulates Islet1 expression in cardiovascular progenitors
      and is required for multiple aspects of cardiogenesis.
AB  - Recent studies have demonstrated that the LIM homeodomain transcription factor
      Islet1 (Isl1) marks pluripotent cardiovascular progenitor cells and is required
      for proliferation, survival, and migration of recently defined second heart field
      progenitors. Factors that are upstream of Isl1 in cardiovascular progenitors have
      not yet been defined. Here we demonstrate that beta-catenin is required for Isl1
      expression in cardiac progenitors, directly regulating the Isl1 promoter.
      Ablation of beta-catenin in Isl1-expressing progenitors disrupts multiple aspects
      of cardiogenesis, resulting in embryonic lethality at E13. beta-Catenin is also
      required upstream of a number of genes required for pharyngeal arch, outflow
      tract, and/or atrial septal morphogenesis, including Tbx2, Tbx3, Wnt11, Shh, and
      Pitx2. Our findings demonstrate that beta-catenin signaling regulates
      proliferation and survival of cardiac progenitors.

PMID- 17519334
TI  - Global and regional drivers of accelerating CO2 emissions.
AB  - CO2 emissions from fossil-fuel burning and industrial processes have been
      accelerating at a global scale, with their growth rate increasing from 1.1% y(-1)
      for 1990-1999 to >3% y(-1) for 2000-2004. The emissions growth rate since 2000
      was greater than for the most fossil-fuel intensive of the Intergovernmental
      Panel on Climate Change emissions scenarios developed in the late 1990s. Global
      emissions growth since 2000 was driven by a cessation or reversal of earlier
      declining trends in the energy intensity of gross domestic product (GDP)
      (energy/GDP) and the carbon intensity of energy (emissions/energy), coupled with
      continuing increases in population and per-capita GDP. Nearly constant or
      slightly increasing trends in the carbon intensity of energy have been recently
      observed in both developed and developing regions. No region is decarbonizing its
      energy supply. The growth rate in emissions is strongest in rapidly developing
      economies, particularly China. Together, the developing and least-developed
      economies (forming 80% of the world's population) accounted for 73% of global
      emissions growth in 2004 but only 41% of global emissions and only 23% of global
      cumulative emissions since the mid-18th century. The results have implications
      for global equity.

PMID- 17519335
TI  - Selectivity in K+ channels is due to topological control of the permeant ion's
      coordinated state.
AB  - The selectivity filter of K+ channels provides specific coordinative interactions
      between dipolar carbonyl ligands, water, and the permeant cation, which allow for
      selective flow of K+ over (most importantly) Na+ across the cell membrane.
      Although a structural viewpoint attributes K+ selectivity to coordination
      geometry provided by the filter, recent molecular dynamics simulation studies
      attribute it to dynamic and unique chemical/electrostatic properties of the
      filter's carbonyl ligands. Here we provide a simple theoretical analysis of K+
      and Na+ complexation with water in the context of simplified binding site models
      and bulk solution. Our analysis reveals that water molecules and carbonyl groups
      can both provide K+ selective environments if equivalent constraints are imposed
      on the coordination number of the complex. Absence of such constraints
      annihilates selectivity, demonstrating that whether a coordinating ligand is a
      water molecule or a carbonyl group, "external" or "topological"
      constraints/forces must be imposed on an ion-coordinated complex to elicit
      selective binding. These forces must inevitably originate from the channel
      protein, because in bulk water, which, by definition, presents a nonselective
      medium, the coordination number is allowed to relax to suit the ion. We show that
      the coordination geometry of K+ channel binding sites is replicated by 8-fold
      complexation of K+ in both water and simplified binding site models due to
      dominance of local interactions within a complex and is thus a requirement for
      topologically constraining the coordination number to a specific value.

PMID- 17519336
TI  - Analyzing the control of mosquito-borne diseases by a dominant lethal genetic
      system.
AB  - Motivated by the failure of current methods to control dengue fever, we formulate
      a mathematical model to assess the impact on the spread of a mosquito-borne viral
      disease of a strategy that releases adult male insects homozygous for a dominant,
      repressible, lethal genetic trait. A dynamic model for the female adult mosquito
      population, which incorporates the competition for female mating between released
      mosquitoes and wild mosquitoes, density-dependent competition during the larval
      stage, and realization of the lethal trait either before or after the larval
      stage, is embedded into a susceptible-exposed-infectious-susceptible human-vector
      epidemic model for the spread of the disease. For the special case in which the
      number of released mosquitoes is maintained in a fixed proportion to the number
      of adult female mosquitoes at each point in time, we derive mathematical formulas
      for the disease eradication condition and the approximate number of released
      mosquitoes necessary for eradication. Numerical results using data for dengue
      fever suggest that the proportional policy outperforms a release policy in which
      the released mosquito population is held constant, and that eradication in
      approximately 1 year is feasible for affected human populations on the order of
      10(5) to 10(6), although the logistical considerations are daunting. We also
      construct a policy that achieves an exponential decay in the female mosquito
      population; this policy releases approximately the same number of mosquitoes as
      the proportional policy but achieves eradication nearly twice as fast.

PMID- 17519337
TI  - Strongly emissive individual DNA-encapsulated Ag nanoclusters as single-molecule
      fluorophores.
AB  - The water-soluble, near-IR-emitting DNA-encapsulated silver nanocluster presented
      herein exhibits extremely bright and photostable emission on the single-molecule
      and bulk levels. The photophysics have been elucidated by intensity-dependent
      correlation analysis and suggest a heavy atom effect of silver that rapidly
      depopulates an excited dark level before quenching by oxygen, thereby conferring
      great photostability, very high single-molecule emission rates, and essentially
      no blinking on experimentally relevant time scales (0.1 to >1,000 ms). Strong
      antibunching is observed from these biocompatible species, which emit >10(9)
      photons before photobleaching. The significant dark-state quantum yield even
      enables bunching from the emissive state to be observed as a dip in the
      autocorrelation curve with only a single detector as the dark state precludes
      emission from the emissive level. These species represent significant
      improvements over existing dyes, and the nonpower law blinking kinetics suggest
      that these very small species may be alternatives to much larger and strongly
      intermittent semiconductor quantum dots.

PMID- 17519338
TI  - Density-equalizing Euclidean minimum spanning trees for the detection of all
      disease cluster shapes.
AB  - Existing disease cluster detection methods cannot detect clusters of all shapes
      and sizes or identify highly irregular sets that overestimate the true extent of
      the cluster. We introduce a graph-theoretical method for detecting arbitrarily
      shaped clusters based on the Euclidean minimum spanning tree of cartogram
      transformed case locations, which overcomes these shortcomings. The method is
      illustrated by using several clusters, including historical data sets from West
      Nile virus and inhalational anthrax outbreaks. Sensitivity and accuracy
      comparisons with the prevailing cluster detection method show that the method
      performs similarly on approximately circular historical clusters and greatly
      improves detection for noncircular clusters.

PMID- 17519339
TI  - Cystic fibrosis transmembrane conductance regulator is vital to sperm fertilizing
      capacity and male fertility.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel,
      mutations of which cause cystic fibrosis, a disease characterized by defective
      Cl(-) and HCO(3)(-) transport. Although >95% of all CF male patients are
      infertile because of congenital bilateral absence of the vas deferens (CBAVD),
      the question whether CFTR mutations are involved in other forms of male
      infertility is under intense debates. Here we report that CFTR is detected in
      both human and mouse sperm. CFTR inhibitor or antibody significantly reduces the
      sperm capacitation, and the associated HCO(3)(-)-dependent events, including
      increases in intracellular pH, cAMP production and membrane hyperpolarization.
      The fertilizing capacity of the sperm obtained from heterozygous CFTR mutant mice
      is also significantly lower compared with that of the wild-type. These results
      suggest that CFTR in sperm may be involved in the transport of HCO(3)(-)
      important for sperm capacitation and that CFTR mutations with impaired CFTR
      function may lead to reduced sperm fertilizing capacity and male infertility
      other than CBAVD.

PMID- 17519340
TI  - Neural signature of fictive learning signals in a sequential investment task.
AB  - Reinforcement learning models now provide principled guides for a wide range of
      reward learning experiments in animals and humans. One key learning (error)
      signal in these models is experiential and reports ongoing temporal differences
      between expected and experienced reward. However, these same abstract learning
      models also accommodate the existence of another class of learning signal that
      takes the form of a fictive error encoding ongoing differences between
      experienced returns and returns that "could-have-been-experienced" if decisions
      had been different. These observations suggest the hypothesis that, for all real
      world learning tasks, one should expect the presence of both experiential and
      fictive learning signals. Motivated by this possibility, we used a sequential
      investment game and fMRI to probe ongoing brain responses to both experiential
      and fictive learning signals generated throughout the game. Using a large cohort
      of subjects (n = 54), we report that fictive learning signals strongly predict
      changes in subjects' investment behavior and correlate with fMRI signals measured
      in dopaminoceptive structures known to be involved in valuation and choice.

PMID- 17519341
TI  - Very high-pressure orogenic garnet peridotites.
AB  - Mantle-derived garnet peridotites are a minor component in many very high
      pressure metamorphic terranes that formed during continental subduction and
      collision. Some of these mantle rocks contain trace amounts of zircon and
      micrometer-sized inclusions. The constituent minerals exhibit pre- and
      postsubduction microstructures, including polymorphic transformation and mineral
      exsolution. Experimental, mineralogical, petrochemical, and geochronological
      characterizations using novel techniques with high spatial, temporal, and energy
      resolutions are resulting in unexpected discoveries of new phases, providing
      better constraints on deep mantle processes.

PMID- 17519342
TI  - Structural elucidation of a novel phosphoglycolipid isolated from six species of
      Halomonas.
AB  - The structure of a new phosphoglycolipid from the halophilic Gram-negative
      bacteria Halomonas elongata ATCC 33173(T), Halomonas eurihalina ATCC 49336(T),
      Halomonas almeriensis CECT 7050(T), strain Sharm (AM238662), Halomonas halophila
      DSM 4770(T), and Halomonas salina ATCC 49509(T) was elucidated by NMR and mass
      spectroscopy studies. In all of the species examined, the polar lipid composition
      consisted of 1,2-diacylglycero-3-phosphorylethanolamine, 1,2-diacylglycero-3
      phosphoryl-glycerol, bisphosphatidyl glycerol, and the new phosphoglycolipid
      PGL1. The structure of PGL1 was established to be (2-(alpha-D-glucopyranosyloxy)
      3-hydroxy-propyl)-phosphatidyl diacylglycerol. C16:0;C18:1 and
      C16:0;C19:cyclopropane are the most abundant acyl chains linked to the
      phosphatidylglycerol moiety of each isolated PGL1. All of the species presenting
      the lipid PGL1 belong to Halomonas rRNA group 1, suggesting that the new
      phosphoglycolipid could be a chemotaxonomic marker of this phylogenetic group.

PMID- 17519344
TI  - Re: "Seasonal associations between weather conditions and suicide--evidence
      against a classic hypothesis".

PMID- 17519345
TI  - Taking the "idio" out of idiopathic pulmonary fibrosis: a call to arms.

PMID- 17519346
TI  - Treatment of tuberculosis in HIV-infected patients: we need to know more.

PMID- 17519347
TI  - Hospitalizations with severe COPD.

PMID- 17519348
TI  - Bronchoscopy should be the first test in the evaluation of patients with a
      pulmonary mass.

PMID- 17519349
TI  - It's all about US: (E)US, (EB)US, and their US(age).

PMID- 17519350
TI  - Food perception with age and its relationship to pleasantness.
AB  - Differences between elderly subjects (n = 46, 61-86 years) and young subjects (n
      = 36, 18-25 years) in food perception and food liking were investigated.
      Intensity and liking ratings were assessed for custard dessert, in which flavor
      enrichment, textural change, and irritant addition were incorporated as
      strategies to compensate for sensory losses with increasing age. The sensory
      acuity (taste, olfaction, irritation, chewing efficiency) of both young and
      elderly subjects was measured with the help of different sensitivity tests. The
      elderly perceived the custards differently from the young, mainly as less intense
      in flavor (cherry/vanilla) and less intense in creaminess/swallowing effort.
      Several of the observed interaction effects were different for the elderly and
      the young. The majority of these differences manifested as lower intensity slopes
      for the elderly. Losses in sensitivity to taste and to olfactory and trigeminal
      stimuli as well as a reduced chewing efficiency were observed on average for the
      elderly compared with the young. Furthermore, subgroups of the elderly were
      observed in which the compensatory strategies flavor enrichment, textural change,
      and irritant addition led to an increase in food liking. However, these subgroups
      did not differ in their sensory acuity. The present study does not support the
      assumption that age-associated changes in food perception-caused by losses in
      sensory acuity-inevitably reduce the food liking of the elderly.

PMID- 17519351
TI  - Mutational evidence that the Arabidopsis MAP kinase MPK6 is involved in anther,
      inflorescence, and embryo development.
AB  - Loss-of-function, dominant-negative, and change-of-function genetic approaches
      were used to investigate the role played by the Arabidopsis mitogen-activated
      protein (MAP) kinase MPK6 throughout development. Plants homozygous for T-DNA
      null alleles of MPK6 displayed reduced male fertility and abnormal anther
      development. In addition, a portion of the seed produced by mpk6 plants was found
      to contain embryos that had burst out of their seed coats. To address potential
      functional redundancy, a dominant-negative version of MPK6 was constructed by
      changing the TEY activation loop motif to the amino acid sequence AEF. Plants
      expressing MPK6AEF via the MPK6 native promoter were found to produce excessive
      stomata, consistent with the recently described role of MPK6 in stomatal
      patterning. A novel floral phenotype characterized by abnormal sepal development
      was also observed in MPK6AEF lines. The gene expression pattern of the MPK6
      native promoter was determined using a YFP-MPK6 fusion construct, and expression
      was observed throughout most plant tissues, consistent with a role for MPK6 in
      multiple developmental processes. The YFP-MPK6 construct was found to rescue the
      fertility phenotype of mpk6 null alleles, indicating that the fusion protein
      retains its biological activity. It was also observed, however, that plants
      expressing YFP-MPK6 displayed reduced apical dominance and a shortening of
      inflorescence internodes. These results suggest that the YFP tag modifies the
      activity of MPK6 in a manner that affects inflorescence development but not
      anther development. Taken together, the present results indicate that MPK6 is
      involved in the regulation of multiple aspects of plant development.

PMID- 17519352
TI  - Nitrate transport and signalling.
AB  - Physiological measurements of nitrate (NO(3)(-)) uptake by roots have defined two
      systems of high and low affinity uptake. In Arabidopsis, genes encoding both of
      these two uptake systems have been identified. Most is known about the high
      affinity transport system (HATS) and its regulation and yet measurements of soil
      NO(3)(-) show that it is more often available in the low affinity range above 1
      mM concentration. Several different regulatory mechanisms have been identified
      for AtNRT2.1, one of the membrane transporters encoding HATS; these include
      feedback regulation of expression, a second component protein requirement for
      membrane targeting and phosphorylation, possibly leading to degradation of the
      protein. These various changes in the protein may be important for a second
      function in sensing NO(3)(-) availability at the surface of the root. Another
      transporter protein, AtNRT1.1 also has a role in NO(3)(-) sensing that, like
      AtNRT2.1, is independent of their transport function. From the range of
      concentrations present in the soil it is proposed that the NO(3)(-)-inducible
      part of HATS functions chiefly as a sensor for root NO(3)(-) availability. Two
      other key NO(3)(-) transport steps for efficient nitrogen use by crops, efflux
      across membranes and vacuolar storage and remobilization, are discussed. Genes
      encoding vacuolar transporters have been isolated and these are important for
      manipulating storage pools in crops, but the efflux system is yet to be
      identified. Consideration is given to how well our molecular and physiological
      knowledge can be integrated as well to some key questions and opportunities for
      the future.

PMID- 17519353
TI  - The Janus kinase 2 is required for expression and nuclear accumulation of cyclin
      D1 in proliferating mammary epithelial cells.
AB  - Using a conditional knockout approach, we previously demonstrated that the Janus
      kinase 2 (Jak2) is crucial for prolactin (PRL) signaling and normal mammary gland
      development. PRL is suggested to synchronously activate multiple signaling
      cascades that emerge on the PRL receptor (PRLR). This study demonstrates that
      Jak2 is essential for the activation of the signal transducer and activator of
      transcription 5 (Stat5) and expression of Cish (cytokine-inducible SH2-containing
      protein), a Stat5-responsive negative regulator of Jak/Stat signaling. However,
      Jak2 is dispensable for the PRL-induced activation of c-Src, focal adhesion
      kinase, and the MAPK pathway. Despite activation of these kinases that are
      commonly associated with proliferative responses, the ablation of Jak2 reduces
      the multiplication of immortalized mammary epithelial cells (MECs). Our studies
      show that signaling through Jak2 controls not only the transcriptional activation
      of the Cyclin D1 gene, but, more importantly, it regulates the accumulation of
      the Cyclin D1 protein in the nucleus by altering the activity of signal
      transducers that mediate the phosphorylation and subsequent nuclear export of
      Cyclin D1. In particular, the levels of activated Akt (protein kinase B) and
      inactive glycogen synthase kinase-3beta (i.e. a kinase that regulates the nuclear
      export and degradation of Cyclin D1) are reduced in MECs lacking Jak2. The
      proliferation of Jak2-deficient MECs can be rescued by expressing of a mutant
      form of Cyclin D1 that cannot be phosphorylated by glycogen synthase kinase-3beta
      and therefore constitutively resides in the nucleus. Besides discriminating Jak2
      dependent and Jak2-independent signaling events emerging from the PRLR, our
      observations provide a possible mechanism for phenotypic similarities between
      Cyclin D1 knockouts and females lacking individual members of the PRLR signaling
      cascade, in particular the PRLR, Jak2, and Stat5.

PMID- 17519354
TI  - Novel regulatory role for human Acf1 in transcriptional repression of vitamin D3
      receptor-regulated genes.
AB  - Hormones and vitamins play integral roles in modulating transcriptional activity
      of members of the nuclear hormone receptor (NR) superfamily. The nuclear receptor
      corepressor protein (N-CoR) is essential for the transcriptional repression by
      unliganded NRs. In an attempt to isolate novel components of the hormone
      signaling pathway, we used a yeast two-hybrid screen and identified human ATP
      utilizing chromatin assembly and remodeling factor 1 (hAcf1) as an N-CoR
      interacting protein. A previously unrecognized function of hAcf1 in the
      repression of euchromatic genes in mammalian cells was found: hAcf1 plays key
      roles in the hormone responsiveness and in the transcriptional repression of
      specific class II NR-regulated genes. First, hormone treatment causes a
      significant release of hAcf1 from its target gene promoters. Second, hAcf1 is
      crucial for stabilizing the endogenous vitamin D receptor-N-CoR repression
      complex and N-CoR itself, in the vitamin D3-regulated IGF binding protein 3 and
      receptor activator of nuclear factor-kappaB ligand gene promoters, respectively.
      Third, RNA interference-mediated reduction of hAcf1 or vitamin D3 treatment
      differentially affects the histone modification profile and the histone occupancy
      in these genes. Together, these results establish that hAcf1 has a critical role
      in the transcriptional repression of specific NR-regulated genes and indicate
      that hAcf1 release and histone H3 and H4 eviction are novel mechanisms in hormone
      induced gene activation.

PMID- 17519355
TI  - Response of SMRT (silencing mediator of retinoic acid and thyroid hormone
      receptor) and N-CoR (nuclear receptor corepressor) corepressors to mitogen
      activated protein kinase kinase kinase cascades is determined by alternative mRNA
      splicing.
AB  - The SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N
      CoR (nuclear receptor corepressor) corepressors are important mediators of
      transcriptional repression by nuclear hormone receptors. SMRT is regulated by
      MAPK kinase kinase (MAPKKK) cascades that induce its release from its receptor
      partners, its export from nucleus to cytoplasm, and derepression of target gene
      expression. Intriguingly, the otherwise closely related N-CoR is refractory to
      MAPKKK signaling under the same conditions. However, both SMRT and N-CoR are
      expressed as a series of alternatively spliced protein variants differing in
      structure and function. We have now characterized the impact of this alternative
      mRNA splicing on the corepressor response to MAPKKK signaling. Whereas the
      SMRTalpha, SMRTtau, and SMRTsp2 splice variants are released from their nuclear
      receptor partners in response to MAPKKK activation, the SMRTsp18 variant, which
      resembles N-CoR in its overall molecular architecture, is relatively refractory
      to this kinase-induced release. Alternative splicing of N-CoR, in contrast, had
      only minimal effects on the resistance of this corepressor to MAPKKK inhibition.
      Notably, all of the SMRT splice variants examined redistributed from nucleus to
      cytoplasm in response to MAPKKK cascade signaling, but none of the N-CoR splice
      variants did so. Different tiers of the MAPKKK cascade hierarchy contributed to
      these different aspects of corepressor regulation, with MAP/ERK kinase kinase 1
      and MAP/ERK kinase 1 regulating subcellular redistribution and ERK2 regulating
      nuclear receptor-corepressor interaction. We conclude that cells can customize
      their transcriptional response to MAPKKK cascade signaling by selective
      expression of the SMRT or N-CoR locus, by selective utilization of a specific
      corepressor splice variant, and by selective exploitation of specific tiers of
      the MAPK cascade.

PMID- 17519356
TI  - A common polymorphism in the bile acid receptor farnesoid X receptor is
      associated with decreased hepatic target gene expression.
AB  - The farnesoid X receptor (FXR or NR1H4) is an important bile-acid-activated,
      transcriptional regulator of genes involved in bile acid, lipid, and glucose
      homeostasis. Accordingly, interindividual variations in FXR expression and
      function could manifest as variable susceptibility to conditions such as
      cholesterol gallstone disease, atherosclerosis, and diabetes. We performed an FXR
      polymorphism discovery analysis of European-, African-, Chinese-, and Hispanic
      Americans and identified two rare gain-of-function variants and a common single
      nucleotide polymorphism resulting in a G-1T substitution in the nucleotide
      adjacent to the translation initiation site (FXR*1B) with population allelic
      frequencies ranging from 2.5 to 12%. In cell-based transactivation assays, FXR*1B
      (-1T) activity was reduced compared with FXR*1A (-1G). This reduced activity for
      FXR*1B resulted from neither decreased translational efficiency nor the potential
      formation of a truncated translational variant. To further define the relevance
      of this polymorphism, gene expression was examined in a human liver bank to
      reveal that levels of the FXR target genes small heterodimer partner and organic
      anion transporting polypeptide 1B3 were significantly reduced in livers harboring
      an FXR*1B allele. These findings are the first to identify the presence of a
      common genetic variant in FXR with functional consequences that could contribute
      to disease risk or therapeutic outcomes.

PMID- 17519357
TI  - Desensitization of the dopamine D1 and D2 receptor hetero-oligomer mediated
      calcium signal by agonist occupancy of either receptor.
AB  - When dopamine D1 and D2 receptors were coactivated in D1-D2 receptor hetero
      oligomeric complexes, a novel phospholipase C-mediated calcium signal was
      generated. In this report, desensitization of this Gq/11-mediated calcium signal
      was demonstrated by pretreatment with dopamine or with the D1-selective agonist
      (+/-)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      hydrobromide (SKF-81297) or the D2-selective agonist quinpirole. Desensitization
      of the calcium signal mediated by D1-D2 receptor hetero-oligomers was initiated
      by agonist occupancy of either receptor subtype even though the signal was
      generated only by occupancy of both receptors. The efficacy, potency, and rate of
      calcium signal desensitization by agonist occupancy of the D1 receptor (t1/2,
      approximately 1 min) was far greater than by the D2 receptor (t1/2, approximately
      10 min). Desensitization of the calcium signal was not mediated by depletion of
      calcium stores or internalization of the hetero-oligomer and was not decreased by
      inhibiting second messenger-activated kinases. The involvement of G protein
      coupled receptor kinases 2 or 3, but not 5 or 6, in the desensitization of the
      calcium signal was shown, occurring through a phosphorylation independent
      mechanism. Inhibition of Gi protein function associated with D2 receptors
      increased D1 receptor-mediated desensitization of the calcium signal, suggesting
      that cross-talk between the signals mediated by the activation of different G
      proteins controlled the efficacy of calcium signal desensitization. Together,
      these results demonstrate the desensitization of a signal mediated only by hetero
      oligomerization of two G protein-coupled receptors that was initiated by agonist
      occupancy of either receptor within the hetero-oligomer, albeit with differences
      in desensitization profiles observed.

PMID- 17519358
TI  - CETP genotypes and HDL-cholesterol phenotypes in the HERITAGE Family Study.
AB  - Associations between cholesteryl ester transfer protein (CETP) polymorphisms and
      high-density lipoprotein cholesterol (HDL-c) levels before and after 20 wk of
      endurance training were investigated in the HERITAGE Family Study. Plasma HDL-c,
      HDL(2)-c, HDL(3)-c, and apolipoprotein (apo)A1 levels were measured, and 13 CETP
      single nucleotide polymorphisms (SNPs) were genotyped in 265 blacks and 486
      whites. Three haplotypes defined by SNPs at the -1337, -971, and -629 sites were
      strongly associated with baseline HDL-c levels in whites. Both C-1337T and C-629A
      were associated with baseline HDL-c (P < 0.001) and apoA1 (P < 0.01) when tested
      separately. However, only C-629A remained significant in a combined model. G-971A
      was not associated with HDL phenotypes, but showed significant interactions with
      C-629A (P = 0.002) on baseline traits. Genotype-by-sex interactions were observed
      at the -629 locus for HDL(3)-c (P = 0.004) and apoA1 (P = 0.02) training
      responses in whites. In women, the -629 A/A homozygotes showed greater increases
      in HDL(3)-c (P = 0.02) and apoA1 (P = 0.02) levels than the other genotypes.
      Finally, apolipoprotein E (APOE) genotype and the CETP C-629A locus contributed
      independently and in additive fashion to the HDL traits, explaining 6.0-8.8% of
      the variance. The CETP -1337T and -629A alleles are associated with higher
      baseline HDL-c and apoA1 levels. The beneficial effects of endurance training on
      plasma HDL(3)-c and apoA1 levels are evident in white women homozygous for the 
      629A allele. The CETP and APOE genotypes account for up to 9% of the variance in
      HDL-c phenotypes in the HERITAGE Family Study.

PMID- 17519359
TI  - Gene expression responses over 24 h to lengthening and shortening contractions in
      human muscle: major changes in CSRP3, MUSTN1, SIX1, and FBXO32.
AB  - Resistance training using lengthening (eccentric) contractions induces greater
      increases in muscle size than shortening (concentric) contractions, but the
      underlying molecular mechanisms are not clear. Using temporal expression
      profiling, we compared changes in gene expression within 24 h of an acute bout of
      each type of contractions conducted simultaneously in the quadriceps of different
      legs. Five healthy young men performed shortening contractions with one leg while
      the contralateral leg performed lengthening contractions. Biopsies were taken
      from both legs before exercise and 3, 6, and 24 h afterwards, in the fed state.
      Expression profiling (n = 3) was performed using a custom-made Affymetrix
      MuscleChip containing probe sets of approximately 3,300 known genes and expressed
      sequence tags expressed in skeletal muscle. We identified 51 transcripts
      differentially regulated between the two exercise modes. Using unsupervised
      hierarchical clustering, we identified four distinct clusters, three of which
      corresponded to unique functional categories (protein synthesis, stress
      response/early growth, and sarcolemmal structure). Using quantitative RT-PCR (n =
      5), we verified expression changes (lengthening/shortening) in SIX1 (3 h, -1.9
      fold, P < 0.001), CSRP3 (6 h, 2.9-fold, P < 0.05), and MUSTN1 (24 h, 4.3-fold, P
      < 0.05). We examined whether FBXO32/atrogin-1/MAFbx, a known regulator of protein
      breakdown and of muscle atrophy was differentially expressed: the gene was
      downregulated after lengthening contractions (3 h, 2.7-fold, P < 0.05; 6 h, 3.3
      fold, P < 0.05; 24 h, 2.3-fold, P < 0.05). The results suggested that lengthening
      and shortening contractions activated distinct molecular pathways as early as 3 h
      postexercise. The molecular differences might contribute to mechanisms underlying
      the physiological adaptations seen with training using the two modes of exercise.

PMID- 17519360
TI  - Dead or alive: gene expression profiles of advanced atherosclerotic plaques from
      autopsy and surgery.
AB  - Since inclusion of atherosclerotic tissues from different sources is often
      indispensable to study the full atherogenic spectrum, we investigated to what
      extent the expression profiles of advanced, stable atherosclerotic lesions
      obtained during autopsy and surgery are comparable. The gene expression profiles
      of human carotids with advanced atherosclerosis obtained at autopsy and at
      vascular surgery were studied by microarray analysis. Expression analysis was
      performed both at the single gene (Rosetta, Gene Ontology) and at the pathway
      level using Ingenuity and Gene Set Enrichment Analysis. In addition, mRNA and
      protein expression levels were validated using quantitative (q) RT-PCR and
      immunohistochemistry on unrelated advanced carotid lesions from autopsy and
      surgery. Microarray analysis indicated that the 97.2% of genes showed similar
      expression levels in advanced atherosclerotic lesions from autopsy and surgery.
      While the expression data revealed no differences in common atherosclerotic
      related pathways such as lipid metabolism and inflammation, the differentially
      expressed genes were mainly involved in basal cell metabolism and hypoxia driven
      pathways. qRT-PCR confirmed the differential expression of hypoxia-driven genes
      VEGF-A (2.3-fold upward arrow), glucose transporter (GLUT)-1 (2.5-fold upward
      arrow), GLUT3 (8.3-fold upward arrow), and hexokinase 1 (2.4-fold upward arrow)
      in autopsy vs. surgical specimens. Immunohistochemistry revealed that the
      transcriptional differences in these hypoxia-related genes were not reflected at
      the protein level. The gene expression profiles of advanced atherosclerotic
      lesions from autopsy and surgery are largely similar. However, >500 genes, mostly
      involved in basal cell metabolism and hypoxia were differentially expressed at
      mRNA, but not at the protein level.

PMID- 17519361
TI  - Differential expression, distribution, and function of PPAR-gamma in the proximal
      and distal colon.
AB  - Suppression of colon carcinogenesis by peroxisome proliferator-activated receptor
      (PPAR)-gamma is likely due to some effect of PPAR-gamma on normal colonic
      epithelial cells. However, our understanding of the effects of PPAR-gamma in such
      cells is limited. We analyzed the abundance, distribution, and function of PPAR
      gamma in epithelial cells isolated from the murine proximal and distal colon.
      Marked differences in PPAR-gamma abundance and distribution were observed,
      suggesting tissue-specific responses. Analysis of PPAR-gamma effects on DNA
      synthesis, formation of preneoplastic lesions, and activation of MAPK signaling
      in proximal and distal colonic epithelial cells in vivo indicates that PPAR-gamma
      regulates both tissue-specific and common responses within the proximal and
      distal colon. Three major functional cohorts of PPAR-gamma target genes were
      identified by genomic profiling of isolated colonic epithelial cells: genes that
      are involved in metabolism, in signaling, and in cellular adhesion and motility.
      Two subsets of PPAR-gamma target genes were differentially expressed in the
      proximal and distal epithelium. Proximal target genes were primarily involved in
      metabolic activities, whereas signal transduction, adhesion, and motility targets
      were more pronounced in the distal colon. Remarkably, those target genes that are
      differentially expressed in the proximal colon were all induced on activation of
      PPAR-gamma, whereas all target genes that are preferentially expressed in the
      distal colon were repressed. Our data indicate that PPAR-gamma exerts both common
      and tissue-specific effects in the colon and challenge the general conclusions
      that PPAR-gamma is induced on differentiation of colonic epithelial cells and
      that this receptor stimulates differentiated function in epithelial cells
      throughout the colon.

PMID- 17519362
TI  - Disruption of insulin-like growth factor-I expression in type IIalphaI collagen
      expressing cells reduces bone length and width in mice.
AB  - It is well established that insulin-like growth factor (IGF)-I is critical for
      the regulation of peak bone mineral density (BMD) and bone width. However, the
      role of systemic vs. local IGF-I is not well understood. To determine the role
      local IGF-I plays in regulating BMD and bone width, we crossed IGF-I flox/flox
      mice with procollagen, typeIIalphaI-Cre mice to generate conditional mutants in
      which chondrocyte-derived IGF-I was disrupted. Bone parameters were measured by
      dual X-ray absorptiometry at 2, 4, 8, and 12 wk of age and peripheral
      quantitative computed tomography at 12 wk of age. Body length, areal BMD, and
      bone mineral content (BMC) were reduced (P < 0.05) between 4 and 12 wk in the
      conditional mutant mice. Bone width was reduced 7% in the vertebrae and femur (P
      < 0.05) of conditional mutant mice at 12 wk. Gains in body length and total body
      BMC and BMD were reduced by 27, 22, and 18%, respectively (P < 0.05) in
      conditional mutant mice between 2 and 4 wk of age. Expression of parathyroid
      hormone related protein, parathyroid hormone receptor, distal-less homeobox (Dlx)
      5, SRY-box containing gene-9, and IGF binding protein (IGFBP)-5 were reduced 27,
      36, 45, 33, and 45%, respectively, in the conditional mutant cartilage (P <
      0.05); however, no changes in Indian hedgehog, Dlx-3, growth hormone receptor,
      IGF-I receptor, and IGFBP-3 expression were observed (P > or = 0.20). In
      conclusion, IGF-I from cells expressing procollagen type IIalphaI regulates bone
      accretion that occurs during postnatal growth period.

PMID- 17519363
TI  - Structural organization of the gap junction network in the cerebral cortex.
AB  - Neurons in mammalian brains are heavily interconnected by specialized junctions
      called chemical synapses. At chemical synapses, signals are transmitted rather
      indirectly between connected neurons with some delay. Recent studies have
      revealed additional channels for neuronal communication, that is, gap junctions.
      As electrical signals are directly transmitted through gap junctions without
      delay, gap junctions can mediate synchronous activities of coupled neurons. In
      the cerebral cortex, both morphological and physiological studies have
      established frequent occurrence of gap junctions between dendrites of GABAergic
      interneurons of particular types. However, it remains unclear how the dendritic
      network of these interneurons is extended three-dimensionally within the tissue
      architecture. The present article reviews recent findings on structural aspects
      of the gap junction network in the cerebral cortex. The three-dimensional
      structure of the network is discussed on a basis of contrasting tissue
      organization in the two cortical areas, the hippocampus and neocortex. The
      controversial issue on the presence and function of distal gap junctions is
      addressed. Quantitative analysis of the distribution of gap junctions along
      dendritic profiles suggests lateral continuity of the network that extends in a
      boundless manner. Functional implications of this lateral continuity are
      discussed with particular reference to variability in local cell assemblies.

PMID- 17519364
TI  - Statins: multiple mechanisms of action in the ischemic brain.
AB  - Although substantial epidemiological studies have failed to find a correlation
      between cholesterol levels and stroke, clinical trials have shown that HMG-CoA
      reductase inhibitors (or statins, the most potent hypocholesterolemic drugs
      available) greatly reduce the incidence of stroke. These clinical observations
      have opened the way to a number of studies of the non-cholesterol-dependent (or
      pleiotropic) effects in animal models of stroke, indicating that the
      neuroprotection is attributable to multiple activities. One of the main
      protective mechanisms elicited by statin administration is the increase in nitric
      oxide bioavailability that regulates cerebral perfusion and improves endothelial
      function, but others include antioxidant properties, the inhibition of
      inflammatory responses, immunomodulatory actions, the regulation of progenitor
      cells, and the stabilization of atherosclerotic plaques. Many of these effects
      are due to the inhibited synthesis of isoprenoid intermediates, which serve as
      lipid attachments for a variety of intracellular signaling molecules. This
      article describes the mechanisms involved in the neuroprotective effects of
      statins.

PMID- 17519365
TI  - The neural basis of inhibition in cognitive control.
AB  - The concept of "inhibition" is widely used in synaptic, circuit, and systems
      neuroscience, where it has a clear meaning because it is clearly observable. The
      concept is also ubiquitous in psychology. One common use is to connote an
      active/willed process underlying cognitive control. Many authors claim that
      subjects execute cognitive control over unwanted stimuli, task sets, responses,
      memories, and emotions by inhibiting them, and that frontal lobe damage induces
      distractibility, impulsivity, and perseveration because of damage to an
      inhibitory mechanism. However, with the exception of the motor domain, the notion
      of an active inhibitory process underlying cognitive control has been heavily
      challenged. Alternative explanations have been provided that explain cognitive
      control without recourse to inhibition as concept, mechanism, or theory. This
      article examines the role that neuroscience can play when examining whether the
      psychological concept of active inhibition can be meaningfully applied in
      cognitive control research.

PMID- 17519366
TI  - Plasticity of the primate prefrontal cortex.
AB  - Cortical plasticity refers to flexible and long-lasting changes in neuronal
      circuitry and information processing, which is caused by learning and experience.
      Although cortical plasticity can be observed in every cortex of the brain, the
      plasticity of the prefrontal cortex (PFC) is particularly important because the
      PFC is involved in various cognitive functions, and its plasticity could lead to
      adaptive changes in the use of other brain regions. Cortical plasticity occurs at
      several levels, from functional molecules to the organization of large areas of
      the brain. Here, the authors focus mainly on the development and remodeling of
      the functional and structural organization of the primate PFC. They discuss how
      the columnar modules of the PFC develop in the immature brain, how these modules
      form a "cognitive field" that is responsible for a specific cognitive function,
      how the cognitive field could be reorganized by training in the mature brain, and
      how monoaminergic systems contribute to these various levels of plasticity. They
      suggest that monoaminergic systems, especially the dopaminergic system, are
      involved in various levels of cortical plasticity, such as behavioral learning
      and learning-dependent cortical remodeling, thereby contributing to the
      reorganization of the cognitive field in the primate PFC.

PMID- 17519367
TI  - The neurodevelopmental impact of prenatal infections at different times of
      pregnancy: the earlier the worse?
AB  - Environmental insults taking place in early brain development may have long
      lasting consequences for adult brain functioning. There is a large body of
      epidemiological data linking maternal infections during pregnancy to a higher
      incidence of psychiatric disorders with a presumed neurodevelopmental origin in
      the offspring, including schizophrenia and autism. Although specific gestational
      windows may be associated with a differing vulnerability to infection-mediated
      disturbances in normal brain development, it still remains debatable whether
      and/or why certain gestation periods may confer maximal risk for
      neurodevelopmental disturbances following the prenatal exposure to infectious
      events. In this review, the authors integrate both epidemiological and
      experimental findings supporting the hypothesis that infection-associated
      immunological events in early fetal life may have a stronger neurodevelopmental
      impact compared to late pregnancy infections. This is because infections in early
      gestation may not only interfere with fundamental neurodevelopmental events such
      as cell proliferation and differentiation, but it may also predispose the
      developing nervous system to additional failures in subsequent cell migration,
      target selection, and synapse maturation, eventually leading to multiple brain
      and behavioral abnormalities in the adult offspring. The temporal dependency of
      the epidemiological link between maternal infections during pregnancy and a
      higher risk for brain disorders in the offspring may thus be explained by
      specific spatiotemporal events in the course of fetal brain development.

PMID- 17519368
TI  - The working memory networks of the human brain.
AB  - Working memory and short-term memory are closely related in their cognitive
      architecture, capacity limitations, and functional neuroanatomy, which only
      partly overlap with those of long-term memory. The author reviews the functional
      neuroimaging literature on the commonalities and differences between working
      memory and short-term memory and the interplay of areas with modality-specific
      and supramodal representations in the brain networks supporting these fundamental
      cognitive processes. Sensory stores in the visual, auditory, and somatosensory
      cortex play a role in short-term memory, but supramodal parietal and frontal
      areas are often recruited as well. Classical working memory operations such as
      manipulation, protection against interference, or updating almost certainly
      require at least some degree of prefrontal support, but many pure maintenance
      tasks involve these areas as well. Although it seems that activity shifts from
      more posterior regions during encoding to more anterior regions during delay,
      some studies reported sustained delay activity in sensory areas as well. This
      spatiotemporal complexity of the short-term memory/working memory networks is
      mirrored in the activation patterns that may explain capacity constraints, which,
      although most prominent in the parietal cortex, seem to be pervasive across
      sensory and premotor areas. Finally, the author highlights open questions for
      cognitive neuroscience research of working memory, such as that of the mechanisms
      for integrating different types of content (binding) or those providing the link
      to long-term memory.

PMID- 17519369
TI  - Neurotransmitters and brain maturation: early paracrine actions of GABA and
      glutamate modulate neuronal migration.
AB  - Migration of neurons from their birthplace to their final destination is an
      extremely important step in brain maturation, and cortical migration disorders
      are the most common brain developmental alteration observed in human patients.
      Among the mechanisms that govern neuronal migration, the neurotransmitters GABA
      and glutamate deserve particular attention: 1) neurotransmitters and receptors
      are expressed early in the developing brain, 2) neurotransmitters may act as
      paracrine signaling molecules in the immature brain, and 3) neurotransmitters
      regulate intracellular calcium required for many cellular functions, including
      cytoskeletal dynamic changes. Thus, many reports reviewed here aimed to
      demonstrate that the activation of specific GABA and glutamate receptors is
      instrumental in cell migration by acting as motility promoting, acceleratory, or
      stop signal. Interestingly, the regulation of migration by neurotransmitters and
      receptors depends on the type of migration (radial, tangential, or chain
      migration), the type of cells (principal glutamatergic neurons vs. GABAergic
      interneurons), and the brain area (neocortex, cerebellum, rostral migratory
      stream). A hypothesis is proposed that these differential actions in different
      cell types arise from a "homeostatic-like" regulation that controls final
      position, timing, and number of cells at destination.

PMID- 17519370
TI  - Prefrontal cortex and long-term memory encoding: an integrative review of
      findings from neuropsychology and neuroimaging.
AB  - Recent findings have led to a growing appreciation of the role of the lateral
      prefrontal cortex (PFC) in episodic long-term memory (LTM). Here, the authors
      will review results from neuropsychological and neuroimaging studies of humans
      and present a framework to explain how different regions of the PFC contribute to
      successful LTM formation. Central to this framework is the idea that different
      regions within the PFC implement different control processes that augment memory
      by enhancing or attenuating memory for certain aspects of a particular item or
      event. Evidence reviewed here suggests that ventrolateral regions of the PFC
      contribute to the ability to select goal-relevant item information, and that this
      processing strengthens the representation of goal-relevant features of items
      during LTM encoding. Dorsolateral regions of the PFC may contribute to the
      ability to organize multiple pieces of information in working memory, thereby
      enhancing memory for associations among items in LTM. Thus, dorsolateral and
      ventrolateral regions of the PFC may implement different control processes that
      support LTM formation in a complementary fashion.

PMID- 17519371
TI  - Questions about ACR accreditation.

PMID- 17519372
TI  - 18FDG uptake in brown fat: potential for false positives.
AB  - CONTEXT: (18)FDG is used widely to enhance PET and PET-CT images. However, this
      radiotracer tends to be taken up by brown fat, which can lead to false-positive
      diagnoses. Purpose To determine which patients, areas of the body and
      circumstances are more likely to be associated with false-positive diagnoses due
      to (18)FDG uptake in brown fat. METHOD: A review of the literature was conducted
      on factors that contribute to false-positive diagnoses caused by (18)FDG uptake
      in brown fat. RESULTS: Brown fat commonly is found in women and children and can
      be located in the supraclavicular, mediastinal, paravertebral and perirenal areas
      of the body. Research has shown that these areas can be sources of a false
      positive diagnosis because of (18)FDG uptake. Studies also have indicated that
      cold climate affects the uptake of (18)FDG, contributing to false-positive
      results on PET-CT examinations. CONCLUSIONS: This literature review should
      stimulate continued research into and awareness of the potential for false
      positive PET findings in women and children during the winter months and in cold
      climates. This information is especially applicable to young female patients
      undergoing PET or PET-CT.

PMID- 17519373
TI  - Breast MR imaging: applications and pitfalls.
AB  - CONTEXT: Contrast-enhanced magnetic resonance (MR) imaging provides better detail
      of the breast than either mammography or ultrasound imaging and can be a valuable
      adjunct to other imaging techniques, particularly for small lesions, in dense or
      augmented breasts and for treatment planning. OBJECTIVE: To illustrate some
      common technical problems encountered with MR imaging of the breast and present
      breast pathologies depicted with MR. RESULTS: Using a case-study approach, the
      authors discuss breast MR imaging difficulties related to hardware, software,
      technologist performance and patient cooperation. They also present examples of
      contralateral breast cancer, recurrent breast carcinoma and local staging of
      breast cancer with MR imaging. Summary MR imaging of the breast has important
      advantages over other techniques, despite occasional technical problems.

PMID- 17519374
TI  - Radiation protection.
AB  - One of radiologic technologists' most important professional obligations is
      protecting patients, other members of the health care team, the public and
      themselves from as much radiation-related harm as possible while also maximizing
      the screening, diagnostic and therapeutic potential of ionizing radiation. This
      article reviews the different types of radiation dose and how radiation affects
      the body. Patient shielding, personnel dosimeters and area monitors are
      discussed, along with beam collimation and filtration. The author also describes
      protocols to protect pregnant patients and pregnant technologists.

PMID- 17519375
TI  - Diagnosis and treatment of carotid artery disease.
AB  - Carotid artery disease (CAD) can cause strokes or even death. Fortunately, some
      of the risk factors for CAD can be controlled, and the disease can be prevented,
      slowed or reversed. This article reviews those risk factors, along with normal
      and abnormal carotid artery anatomy, techniques for imaging the carotid arteries,
      treatment options for CAD and the roles of specialists who diagnose and treat it.
      The article concludes with a look at promising new and alternative treatments.

PMID- 17519376
TI  - Documentation for mammographers.
AB  - The mammographer is the vital link in relaying pertinent patient information to
      the radiologist at the time of the breast imaging examination or procedure. All
      relevant breast health history and areas of clinical concern should be documented
      carefully and precisely in the patient's record. The mammographer also is
      directly responsible for accurate and timely recording of quality control
      equipment function tests and the corrective actions taken. This article supplies
      mammographers with tools to complete effective and consistent documentation as a
      basis for continuity of patient care.

PMID- 17519377
TI  - Radiograph reflects poor practice.

PMID- 17519378
TI  - Obesity creates imaging obstacles.

PMID- 17519379
TI  - An enlightening event.

PMID- 17519380
TI  - Developmental dysplasia of the hip.

PMID- 17519381
TI  - Patellar imaging.

PMID- 17519382
TI  - Iodine 131 uptake related to hair dyeing.

PMID- 17519383
TI  - Minimizing distortion with geometry.

PMID- 17519384
TI  - Barium enema examination/examen de enema de bario.

PMID- 17519385
TI  - Applicability of the dopamine and rate hypotheses in explaining the differences
      in behavioral pharmacology of the chloro-benztropine analogs: studies conducted
      using intracerebral microdialysis and population pharmacodynamic modeling.
AB  - Previous studies indicated that the chloro-benztropine analogs differed
      significantly in their cocaine-like activity, which was not expected based on the
      similarity in their in vitro binding affinity and functional potency at the
      dopamine transporter (DAT). The present study was designed to extend the
      understanding of the involvement of both pharmacokinetic and pharmacodynamic
      factors in mediating the behavioral differences among these analogs. The
      pharmacokinetics of 3'-chloro-3alpha-(diphenylmethoxy)tropane (3'-Cl BZT), the
      analog showing a cocaine-like behavioral profile in rodents, was compared with
      previously reported pharmacokinetic characteristics of cocaine and 4',4''
      dichloro-3alpha-(diphenylmethoxy)tropane (4',4''-diCl BZT), an analog totally
      devoid of cocaine-like actions. Microdialysis studies in rats were conducted to
      determine whether 3'-Cl and 4',4''-diCl BZT differed significantly in their
      effect on nucleus accumbens extracellular dopamine levels, with cocaine serving
      as a reference. A mechanistic model based on DAT association/dissociation
      kinetics was used to describe the time delay between the plasma concentrations of
      the chloro-analogs and their dopaminergic effects. 3'-Cl BZT had plasma
      elimination half-life of 1.9 h versus 0.5 and 21.1 h for cocaine and 4',4''-diCl
      BZT, respectively. 4',4''-diCl BZT increased the DA levels at a slower rate and
      to a significantly lower extent relative to 3'-Cl BZT that were, in turn, lower
      than cocaine. The duration of dopamine elevation was as follows: 4',4''-diCl BZT
      > 3'-Cl BZT > cocaine. The model indicated faster association and dissociation
      with DAT for 3'-Cl BZT relative to 4',4''-diCl BZT. The present results indicate
      that behavioral differences among the chloro-analogs may be explainable based on
      both the dopamine and rate hypotheses of drug abuse.

PMID- 17519386
TI  - PDE4B5, a novel, super-short, brain-specific cAMP phosphodiesterase-4 variant
      whose isoform-specifying N-terminal region is identical to that of cAMP
      phosphodiesterase-4D6 (PDE4D6).
AB  - The cAMP-specific phosphodiesterase-4 (PDE4) gene family is the target of several
      potential selective therapeutic inhibitors. The four PDE4 genes generate several
      distinct protein-coding isoforms through the use of alternative promoters and 5'
      coding exons. Using mouse transcripts, we identified a novel, super-short isoform
      of human PDE4B encoding a novel 5' terminus, which we label PDE4B5. The protein
      coding region of the novel 5' exon is conserved across vertebrates, chicken,
      zebrafish, and fugu. Reverse-transcription-polymerase chain reaction (PCR) and
      quantitative (PCR) measurements show that this isoform is brain-specific. The
      novel protein is 58 +/- 2 kDa; it has cAMP hydrolyzing enzymatic activity and is
      inhibited by PDE4-selective inhibitors rolipram and cilomilast (Ariflo). Confocal
      and subcellular fractionation analyses show that it is distributed predominantly
      and unevenly within the cytosol. The 16 novel N-terminal residues of PDE4B5 are
      identical to the 16 N-terminal residues of the super-short isoform of PDE4D
      (PDE4D6), which is also brain-specific. PDE4B5 is able to bind the scaffold
      protein DISC1, whose gene has been linked to schizophrenia. Microarray expression
      profiling of the PDE4 gene family shows that specific PDE4 genes are enriched in
      muscle and blood fractions; however, only by monitoring the individual isoforms
      is the brain specificity of the super-short PDE4D and PDE4B isoforms revealed.
      Understanding the distinct tissue specificity of PDE4 isoforms will be important
      for understanding phosphodiesterase biology and opportunities for therapeutic
      intervention.

PMID- 17519387
TI  - ACP-103, a 5-hydroxytryptamine 2A receptor inverse agonist, improves the
      antipsychotic efficacy and side-effect profile of haloperidol and risperidone in
      experimental models.
AB  - Dopamine D(2) receptor antagonism contributes to the therapeutic action of
      antipsychotic drugs (APDs) but also produces undesirable side effects, including
      extrapyramidal motor deficits, cognitive dulling, and prolactinemia. The
      introduction of atypical APDs was a significant advancement in the treatment of
      schizophrenia. Whereas these agents are D(2) receptor antagonists, they are also
      potent 5-hydroxytryptamine (5-HT)(2A) receptor inverse agonists, a feature that
      may explain their improved efficacy and tolerability. Recently, we reported that
      N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2
      methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP
      103), a novel selective 5-HT(2A) receptor inverse agonist that fails to bind D(2)
      receptors, is active in several models predictive of antipsychotic activity.
      Using ACP-103, we tested the hypothesis that combining high levels of 5-HT(2A)
      inverse agonism with low levels of D(2) antagonism would result in a favorable
      interaction, such that antipsychotic efficacy could be achieved with reduced D(2)
      receptor-related adverse effects. Here we show that ACP-103 1) potently inhibited
      head-twitching produced by the 5-HT(2A/2C) receptor agonist (+/-)-2,5-dimethoxy-4
      iodoamphetamine, 2) increased the potency of haloperidol against amphetamine
      induced hyperactivity, 3) interacted synergistically with haloperidol or
      risperidone to suppress hyperactivity induced by the N-methyl-d-aspartate
      receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), and, by contrast,
      4) attenuated haloperido-l- or risperidone-induced prolactinemia. ACP-103 also
      attenuated catalepsy produced by haloperidol or risperidone. However, the doses
      that were required for this effect were higher than would be expected for a 5
      HT(2A) receptor-mediated mechanism. These data indicate that utilizing ACP-103 as
      an adjunctive therapy to currently used APDs may result in enhanced antipsychotic
      efficacy while reducing adverse effects including those attributable to D(2)
      receptor antagonism.

PMID- 17519388
TI  - High T-cell response to human cytomegalovirus induces chemokine-mediated
      endothelial cell damage.
AB  - Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases
      that involve vascular endothelial damage, including vascular disease and chronic
      transplant rejection. We previously reported that the host CD4(+) T-cell response
      to CMV antigen presented by endothelial cells can produce interferon-gamma and
      tumor necrosis factor-alpha at levels sufficient to drive induction of
      fractalkine, a key marker of inflammation, in endothelial cells. In this work, we
      report that donors with high frequencies of antigen-specific T cells to CMV (high
      responders) induce higher levels of activation-associated chemokines such as
      fractalkine, RANTES (regulated on activation, normal T cell expressed and
      secreted), and macrophage inflammatory protein-1beta, together with cell-adhesion
      markers in endothelial cells compared with donors with low levels of CMV-specific
      T cells (low responders). High-responder cultures had higher levels of leukocyte
      recruitment and adherence to the endothelial monolayers associated with
      progressive damage and loss of the endothelial cells. These processes that led to
      endothelial destruction only required viral antigen and did not require
      infectious virus. Our findings further support that CMV may represent one member
      of a class of persistent pathogens in which a high antigen-specific T-cell
      response defines an important risk factor for development of chronic inflammation
      and endothelial cell injury.

PMID- 17519390
TI  - Splenic CD19-CD35+B220+ cells function as an inducer of follicular dendritic cell
      network formation.
AB  - Follicular dendritic cells (FDCs) form a reticular FDC network in the lymphoid
      follicle that is essential for the retention and presentation of native antigens
      in the form of antigen-antibody immune complexes (ICs) to B cells during
      secondary immune response. Although the presence of migrating precursors of FDCs
      has been hypothesized, their entity has not been elucidated. Here we report the
      identification of murine splenic CD19(-)CD11c(-)CD35(+)B220(+) cells as an
      inducer of FDC network formation. We demonstrated that CD19(-)-CD11c(
      )CD35(+)B220(+) cells, together with stromal cells, had the remarkable ability to
      form lymphoid-follicle-like structures that contained B220(+)FDC-M1(+) reticular
      cells originally derived from CD19(-)-CD11c(-)CD35(+)B220(+) cells in the CD35(+)
      reticulum. Our results indicate that CD19(-)CD11c(-)CD35(+)B220(+) cells function
      as an inducer of FDC network formation and that the interaction between CD19(
      )CD11c(-)CD35(+)B220(+) cells and stromal cells is required to initiate lymphoid
      follicle formation.

PMID- 17519391
TI  - A score test for linkage analysis of ordinal traits based on IBD sharing.
AB  - Statistical methods for linkage analysis are well established for both binary and
      quantitative traits. However, numerous diseases including cancer and psychiatric
      disorders are rated on discrete ordinal scales. To analyze pedigree data with
      ordinal traits, we recently proposed a latent variable model which has higher
      power to detect linkage using ordinal traits than methods using the dichotomized
      traits. The challenge with the latent variable model is that the likelihood is
      usually very complicated, and as a result, the computation of the likelihood
      ratio statistic is too intensive for large pedigrees. In this paper, we derive a
      computationally efficient score statistic based on the identity-by-decent sharing
      information between relatives. Using simulation studies, we examined the
      asymptotic distribution of the test statistic and the power of our proposed test
      under various levels of heritability. We compared the computing time as well as
      power of the score test with the likelihood ratio test. We then applied our
      method for the Collaborative Study on the Genetics of Alcoholism and performed a
      genome scan to map susceptibility genes for alcohol dependence. We found a strong
      linkage signal on chromosome 4.

PMID- 17519389
TI  - Pathobiology of ALK+ anaplastic large-cell lymphoma.
AB  - Anaplastic large-cell lymphoma (ALCL) was initially recognized on the basis of
      morphologic features and the consistent expression of CD30. It then became
      evident that the majority of these tumors are derived from lymphoid cells of T or
      null immunophenotype. The subsequent finding that t(2;5)(p23;q35) occurs in 40%
      to 60% of ALCL patients established a distinct clinicopathologic entity. This
      chromosomal translocation induces the formation of the chimeric protein
      nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which possesses significant
      oncogenic potential resulting from the constitutive activation of the tyrosine
      kinase ALK. In addition to its specific pathophysiologic events, NPM-ALK
      expressing lymphoma presents with consistent clinical manifestations. Only 13
      years after the identification of NPM-ALK, tremendous progress has been made in
      our understanding of this molecule because of the relentless efforts of multiple
      investigators who have dissected its biologic roles using in vitro and in vivo
      experimental models. Several upstream modulators, cross-reacting oncogenes, and
      downstream effectors of NPM-ALK have been identified and characterized.
      Understanding these interacting oncogenic systems is expected to facilitate the
      design of new therapeutic strategies and agents. In this review, we briefly
      discuss ALCL and focus on NPM-ALK.

PMID- 17519392
TI  - A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents
      a candidate causal mutation for coat color dilution in dogs.
AB  - Coat color dilution in several breeds of dog is characterized by a specific
      pigmentation phenotype and sometimes accompanied by hair loss and recurrent skin
      inflammation, the so-called color dilution alopecia or black hair follicular
      dysplasia. Coat color dilution (d) is inherited as a Mendelian autosomal
      recessive trait. In a previous study, MLPH polymorphisms showed perfect
      cosegregation with the dilute phenotype within breeds. However, different dilute
      haplotypes were found in different breeds, and no single polymorphism was
      identified in the coding sequence that was likely to be causative for the dilute
      phenotype. We resequenced the 5'-region of the canine MLPH gene and identified a
      strong candidate single nucleotide polymorphism within the nontranslated exon 1,
      which showed perfect association to the dilute phenotype in 65 dilute dogs from 7
      different breeds. The A/G polymorphism is located at the last nucleotide of exon
      1 and the mutant A-allele is predicted to reduce splicing efficiency 8-fold. An
      MLPH mRNA expression study using quantitative reverse transcriptase-polymerase
      chain reaction confirmed that dd animals had only about approximately 25% of the
      MLPH transcript compared with DD animals. These results provide preliminary
      evidence that the reported regulatory MLPH mutation might represent a causal
      mutation for coat color dilution in dogs.

PMID- 17519393
TI  - Dopamine modulation of emotional processing in cortical and subcortical neural
      circuits: evidence for a final common pathway in schizophrenia?
AB  - The neural regulation of emotional perception, learning, and memory is essential
      for normal behavioral and cognitive functioning. Many of the symptoms displayed
      by individuals with schizophrenia may arise from fundamental disturbances in the
      ability to accurately process emotionally salient sensory information. The
      neurotransmitter dopamine (DA) and its ability to modulate neural regions
      involved in emotional learning, perception, and memory formation has received
      considerable research attention as a potential final common pathway to account
      for the aberrant emotional regulation and psychosis present in the schizophrenic
      syndrome. Evidence from both human neuroimaging studies and animal-based research
      using neurodevelopmental, behavioral, and electrophysiological techniques have
      implicated the mesocorticolimbic DA circuit as a crucial system for the encoding
      and expression of emotionally salient learning and memory formation. While many
      theories have examined the cortical-subcortical interactions between prefrontal
      cortical regions and subcortical DA substrates, many questions remain as to how
      DA may control emotional perception and learning and how disturbances linked to
      DA abnormalities may underlie the disturbed emotional processing in
      schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the
      amygdala-prefrontal cortical circuit as an important processor of emotionally
      salient information and how neurodevelopmental perturbances within this circuitry
      may lead to dysregulation of DAergic modulation of emotional processing and
      learning along this cortical-subcortical emotional processing circuit.

PMID- 17519394
TI  - Perfluoroalkyl acids: a review of monitoring and toxicological findings.
AB  - In recent years, human and wildlife monitoring studies have identified
      perfluoroalkyl acids (PFAA) worldwide. This has led to efforts to better
      understand the hazards that may be inherent in these compounds, as well as the
      global distribution of the PFAAs. Much attention has focused on understanding the
      toxicology of the two most widely known PFAAs, perfluorooctanoic acid, and
      perfluorooctane sulfate. More recently, research was extended to other PFAAs.
      There has been substantial progress in understanding additional aspects of the
      toxicology of these compounds, particularly related to the developmental
      toxicity, immunotoxicity, hepatotoxicity, and the potential modes of action. This
      review provides an overview of the recent advances in the toxicology and mode of
      action for PFAAs, and of the monitoring data now available for the environment,
      wildlife, and humans. Several avenues of research are proposed that would further
      our understanding of this class of compounds.

PMID- 17519395
TI  - Neurotoxic mechanisms of electrophilic type-2 alkenes: soft soft interactions
      described by quantum mechanical parameters.
AB  - Conjugated Type-2 alkenes, such as acrylamide (ACR), are soft electrophiles that
      produce neurotoxicity by forming adducts with soft nucleophilic sulfhydryl groups
      on proteins. Soft-soft interactions are governed by frontier molecular orbital
      characteristics and can be defined by quantum mechanical parameters such as
      softness (sigma) and chemical potential (mu). The neurotoxic potency of ACR is
      likely related to the rate of adduct formation, which is reflected in values of
      sigma. Correspondingly, differences in mu, the ability of a nucleophile to
      transfer electrons to an electrophile, could determine protein targets of these
      chemicals. Here, sigma and mu were calculated for a series of structurally
      similar Type-2 alkenes and their potential sulfhydryl targets. Results show that
      N-ethylmaleimide, acrolein and methylvinyl ketone were softer electrophiles than
      methyl acrylate or ACR. Softness (sigma) was closely correlated to corresponding
      second-order rate constants (k(2)) for electrophile reactions with sulfhydryl
      groups on N-acetyl-L-cysteine (NAC). The rank order of softness was also directly
      related to neurotoxic potency as determined by impairment of synaptosomal
      function and sulfhydryl loss. Calculations of mu showed that the thiolate state
      of several cysteine analogs was the preferred nucleophilic target of alkene
      electrophiles. In addition, mu was directly related to the thiolate rate constant
      (k) for the reaction of the Type-2 alkenes with the cysteine compounds. Finally,
      in accordance with respective mu values, we found that NAC, but not N-acetyl-L
      lysine, protected synaptosomes from toxicity. These findings suggest that the
      neurotoxicity of ACR and its conjugated alkene analogs is related to
      electrophilic softness and that the thiolate state of cysteine residues is the
      corresponding adduct target.

PMID- 17519396
TI  - Transgenic rescue of methotrexate-induced teratogenicity in Drosophila
      melanogaster.
AB  - The folic acid analog methotrexate (MTX), a competitive inhibitor of
      dihydrofolate reductase (DHFR), is used to treat a variety of cancers and
      autoimmune disorders. However, MTX also causes a wide range of toxic effects in
      healthy cells and is an established teratogen. Efforts to "rescue" the defects
      caused by MTX by administering a folate analog or by transgenic expression of a
      DHFR with an altered affinity for MTX have been attempted in a variety of mammals
      but limited protection was conferred. As a result, our understanding of the
      effect of MTX at the molecular genetic level remains incomplete and, in addition,
      continued mammalian sacrifice is not ideal. Due to the similarity of teratogenic
      effects produced by MTX in Drosophila melanogaster these insects were transformed
      with DHFR alleles to determine if rescue could be achieved. The resulting "MTX
      resistant" flies were subsequently used to investigate changes in gene expression
      in response to MTX using semiquantitative reverse transcription PCR. The majority
      (12/14) of key transcripts that were affected in MTX-exposed females including
      transcripts involved in cell cycle, defense response, and transport were
      "rescued" in the "MTX-resistant" transgenic flies. These studies illustrate the
      utility of this invertebrate model for the investigation of molecular effects of
      MTX-induced teratogenicity, MTX-resistant DHFRs for gene therapy techniques, and
      teratogenic protection.

PMID- 17519397
TI  - Noninherited risk factors and congenital cardiovascular defects: current
      knowledge: a scientific statement from the American Heart Association Council on
      Cardiovascular Disease in the Young: endorsed by the American Academy of
      Pediatrics.
AB  - Prevention of congenital cardiovascular defects has been hampered by a lack of
      information about modifiable risk factors for abnormalities in cardiac
      development. Over the past decade, there have been major breakthroughs in the
      understanding of inherited causes of congenital heart disease, including the
      identification of specific genetic abnormalities for some types of malformations.
      Although relatively less information has been available on noninherited
      modifiable factors that may have an adverse effect on the fetal heart, there is a
      growing body of epidemiological literature on this topic. This statement
      summarizes the currently available literature on potential fetal exposures that
      might alter risk for cardiovascular defects. Information is summarized for
      periconceptional multivitamin or folic acid intake, which may reduce the risk of
      cardiac disease in the fetus, and for additional types of potential exposures
      that may increase the risk, including maternal illnesses, maternal therapeutic
      and nontherapeutic drug exposures, environmental exposures, and paternal
      exposures. Information is highlighted regarding definitive risk factors such as
      maternal rubella; phenylketonuria; pregestational diabetes; exposure to
      thalidomide, vitamin A cogeners, or retinoids; and indomethacin tocolysis.
      Caveats regarding interpretation of possible exposure-outcome relationships from
      case-control studies are given because this type of study has provided most of
      the available information. Guidelines for prospective parents that could reduce
      the likelihood that their child will have a major cardiac malformation are given.
      Issues related to pregnancy monitoring are discussed. Knowledge gaps and future
      sources of new information on risk factors are described.

PMID- 17519398
TI  - Genetic basis for congenital heart defects: current knowledge: a scientific
      statement from the American Heart Association Congenital Cardiac Defects
      Committee, Council on Cardiovascular Disease in the Young: endorsed by the
      American Academy of Pediatrics.
AB  - The intent of this review is to provide the clinician with a summary of what is
      currently known about the contribution of genetics to the origin of congenital
      heart disease. Techniques are discussed to evaluate children with heart disease
      for genetic alterations. Many of these techniques are now available on a clinical
      basis. Information on the genetic and clinical evaluation of children with
      cardiac disease is presented, and several tables have been constructed to aid the
      clinician in the assessment of children with different types of heart disease.
      Genetic algorithms for cardiac defects have been constructed and are available in
      an appendix. It is anticipated that this summary will update a wide range of
      medical personnel, including pediatric cardiologists and pediatricians, adult
      cardiologists, internists, obstetricians, nurses, and thoracic surgeons, about
      the genetic aspects of congenital heart disease and will encourage an
      interdisciplinary approach to the child and adult with congenital heart disease.

PMID- 17519399
TI  - Population pharmacokinetics of tigecycline in healthy volunteers.
AB  - Tigecycline, a novel glycylcycline, possesses broad-spectrum antimicrobial
      activity. A structural population pharmacokinetic model for tigecycline was
      developed based on data pooled from 5 phase I studies. Intravenous tigecycline
      was administered as single (12.5-300 mg) or multiple (25-100 mg) doses every 12
      hours for up to 10 days. Three-compartment models with zero-order input and first
      order elimination separately described the single- or multiple-dose full-profile
      data. Additional models were evaluated using a subset of the phase I data
      mimicking the phase II/III trial sparse-sampling scheme and dosage. A 2
      compartment model best described the reduced phase I data following single or
      multiple doses and provided reliably accurate estimates of tigecycline AUC(0-12).
      This modeling supported phase II/III population pharmacokinetic model development
      to further determine individual patient tigecycline exposures for safety and
      efficacy analyses.

PMID- 17519400
TI  - Steady-state pharmacokinetics of emtricitabine and tenofovir disoproxil fumarate
      administered alone and in combination in healthy volunteers.
AB  - The approved antiretroviral drugs, emtricitabine and tenofovir disoproxil
      fumarate, were considered good candidates for a fixed-dose combination product
      that could be administered as a single pill once daily (qd), thereby simplifying
      existing treatment regimens and promoting patient adherence. As both drugs are
      extensively renally eliminated, a randomized, 3-way crossover study was conducted
      in 19 healthy volunteers to formally evaluate the potential pharmacokinetic
      interaction when the drugs are administered alone and together (ie, 200 mg
      emtricitabine qd for 7 days, 300 mg tenofovir disoproxil fumarate qd for 7 days,
      and 200 mg emtricitabine plus 300 mg tenofovir disoproxil fumarate qd for 7 days)
      with no washout between treatments. Steady-state pharmacokinetic parameters
      (AUC(tau), C(max), and C(min)) of emtricitabine and tenofovir (as tenofovir
      disoproxil fumarate) in combination were essentially equivalent versus each drug
      alone, providing a pharmacokinetic rationale for combining these products in
      emtricitabine/tenofovir disoproxil fumarate fixed-dose tablets.

PMID- 17519401
TI  - The cover. Cattleya Orchid and Three Brazilian Hummingbirds.

PMID- 17519402
TI  - A piece of my mind. Don't sleep with your chickens.

PMID- 17519403
TI  - Antimalarial drugs--here and on the horizon.

PMID- 17519404
TI  - Malaria researchers target mosquitoes.

PMID- 17519405
TI  - Intensive glucose control in elderly adults.

PMID- 17519406
TI  - Intensive glucose control in elderly adults.

PMID- 17519407
TI  - Malaria prevention measures in coalition troops in Afghanistan.

PMID- 17519408
TI  - Statins and regression of coronary atherosclerosis.

PMID- 17519409
TI  - Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the
      treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized
      controlled trial.
AB  - CONTEXT: In areas where Plasmodium falciparum and Plasmodium vivax coexist and
      treatments for the 2 species differ, misdiagnosis can lead to poor outcomes in
      either disease. A unified therapy effective against both species would reduce
      reliance on species-specific diagnosis, which in many areas is difficult to
      maintain. The antifolates are an important and affordable antimalarial class to
      which it is often assumed P vivax malaria is intrinsically resistant. OBJECTIVE:
      To test the relative efficacy and safety of 2 antifolate drugs against P vivax
      malaria and compare each with chloroquine. DESIGN, SETTING, AND PATIENTS: An open
      label randomized controlled trial comparing chloroquine, sulfadoxine
      pyrimethamine, and chlorproguanil-dapsone for the treatment of P vivax malaria
      was conducted in eastern Afghanistan and northwestern Pakistan, areas in which P
      vivax malaria predominates. A total of 20,410 patients older than 3 years were
      screened; 767 patients (315 in Pakistan and 452 in Afghanistan) with confirmed P
      vivax malaria were enrolled and followed up daily for 4 days, then weekly for 28
      days, between March 2004 and June 2006. MAIN OUTCOME MEASURES: Complete clearance
      of parasites with no recrudescence by day 14. Secondary outcomes included being
      parasite-free by day 28, clinical failure, and anemia. RESULTS: By day 14, only 1
      patient in the sulfadoxine-pyrimethamine group had parasites. By day 28, failure
      rates were found in 2 of 153 patients (1.3%) in the chloroquine group, 5 of 290
      patients (1.7%) in the sulfadoxine-pyrimethamine group, and 27 of 272 patients
      (9.9%) in the chlorproguanil-dapsone group. Chlorproguanil-dapsone was less
      effective than sulfadoxine-pyrimethamine (adjusted odds ratio [OR], 6.4; 95%
      confidence interval [CI], 2.4-17.0; P<.001) and chloroquine (adjusted OR, 8.4;
      95% CI, 2.0-36.5; P = .004). Chloroquine and sulfadoxine-pyrimethamine were
      equivalent in efficacy at day 28 (adjusted OR, 1.3; 95% CI, 0.3-7.0; P = .73).
      Chloroquine cleared gametocytes and asexual parasites more rapidly than
      sulfadoxine-pyrimethamine or chlorproguanil-dapsone did. All drugs were well
      tolerated. CONCLUSIONS: Although chloroquine remains the drug of choice,
      antifolates are effective against P vivax malaria in South Asia. These drugs may
      be appropriate for unified treatment where species-specific diagnosis is
      unavailable, most likely in combination with other drugs. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00158561.

PMID- 17519410
TI  - Combination therapy for uncomplicated falciparum malaria in Ugandan children: a
      randomized trial.
AB  - CONTEXT: Combination therapy is now widely advocated as first-line treatment for
      uncomplicated malaria in Africa. However, it is not clear which treatment
      regimens are optimal or how to best assess comparative efficacies in highly
      endemic areas. OBJECTIVE: To compare the efficacy and safety of 3 leading
      combination therapies for the treatment of uncomplicated malaria. DESIGN,
      SETTING, AND PARTICIPANTS: Single-blind randomized clinical trial, conducted
      between November 2004 and June 2006, of treatment for all episodes of
      uncomplicated malaria in children in an urban community in Kampala, Uganda. A
      total of 601 healthy children (aged 1-10 years) were randomly selected and were
      followed up for 13 to 19 months, receiving all medical care at the study clinic.
      INTERVENTIONS: Study participants were randomized to receive 1 of 3 combination
      therapies (amodiaquine plus sulfadoxine-pyrimethamine, amodiaquine plus
      artesunate, or artemether-lumefantrine) when diagnosed with their first episode
      of uncomplicated malaria. The same assigned treatment was given for all
      subsequent episodes. MAIN OUTCOME MEASURE: 28-Day risk of parasitological failure
      (unadjusted and adjusted by genotyping to distinguish recrudescence from new
      infection) for each episode of uncomplicated malaria treated with study drugs.
      RESULTS: Of enrolled children, 329 of 601 were diagnosed with at least 1 episode
      of uncomplicated malaria, and 687 episodes of Plasmodium falciparum malaria were
      treated with study drugs. The 28-day risk of treatment failure (unadjusted by
      genotyping) for individual episodes of malaria were 26.1% (95% CI, 21.1%-32.1%)
      for amodiaquine plus sulfadoxine-pyrimethamine, 17.4% (95% CI, 13.1%-23.1%) for
      amodiaquine plus artesunate, and 6.7% (95% CI, 3.9%-11.2%) for artemether
      lumefantrine (P<.05 for all pairwise comparisons). When only recrudescent
      treatment failures were considered, the risks of failure were 14.1% (95% CI,
      10.3%-19.2%), 4.6% (95% CI, 2.5%-8.3%), and 1.0% (95% CI, 0.3%-4.0%) for the same
      order of study drugs, respectively (P< or =.008 for all pairwise comparisons,
      except amodiaquine plus artesunate vs artemether-lumefantrine, P = .05). There
      were no deaths or cases of severe malaria. Significant reductions in anemia (9.3%
      [95% CI, 7.0%-12.0%] at enrollment vs 0.6% [95% CI, 0.1%-2.2%] during the last 2
      months of follow-up; P<.001) and asymptomatic parasitemia (18.6% [95% CI, 15.5%
      22.1%] at enrollment vs 2.3% [95% CI, 1.5%-3.5%] during the last 2 months of
      follow-up; P<.001) were observed according to routine testing. CONCLUSIONS:
      Artemether-lumefantrine was the most efficacious treatment for uncomplicated
      malaria in the study population. With all study regimens, the provision of prompt
      and reasonably effective facility-based treatment was associated with good
      outcomes in long-term health measures. TRIAL REGISTRATION: isrctn.org Identifier:
      ISRCTN37517549.

PMID- 17519411
TI  - Hemoglobin variants and disease manifestations in severe falciparum malaria.
AB  - CONTEXT: The geographical distributions of hemoglobin S (HbS), hemoglobin C
      (HbC), and alpha+-thalassemia (-alpha) strongly suggest balancing selection with
      malaria. However, whereas several studies indicate that the HbS carrier state
      protects against all major forms of clinical malaria, malaria protection on
      clinical grounds has been more difficult to confirm for HbC and -alpha, and
      questions remain as to whether it applies to all forms of the disease. OBJECTIVE:
      To assess the association between major clinical forms of severe falciparum
      malaria and HbS, HbC, and -alpha. DESIGN, SETTING, AND PARTICIPANTS: Case-control
      study of 2591 children with severe falciparum malaria enrolled at a tertiary
      referral center in Ghana, West Africa, and 2048 age-, sex-, and ethnicity-matched
      control participants recruited by community surveys. MAIN OUTCOME MEASURES:
      Frequencies of HbS, HbC, and -alpha in patients and controls, including
      stratifications of patients for signs of disease. RESULTS: Patients presented
      with partly overlapping signs of disease, including severe anemia (64%), cerebral
      malaria (22%), respiratory distress (30%), hyperparasitemia (32%), prostration
      (52%), acidosis (59%), and hyperlactatemia (56%). Carrier states of HbS, HbC, and
      -alpha were found in 1.4%, 9.4%, and 25.2% of the patients, respectively, and
      14.8%, 8.7%, and 27.3% of controls. The HbS carrier state was negatively
      associated with all forms of the disease studied (overall odds ratio [OR], 0.08;
      95% confidence interval [CI], 0.06-0.12). The HbC carrier state showed a negative
      association selectively with cerebral malaria (OR, 0.64; 95% CI, 0.45-0.91), and
      the -alpha carrier state showed a negative association selectively with severe
      anemia (OR, 0.82; 95% CI, 0.69-0.96). CONCLUSION: Whereas the HbS carrier state
      was found to be negatively associated with all major forms of severe falciparum
      malaria, the negative associations of the carrier states of HbC and -alpha
      appeared to be limited to cerebral malaria and severe anemia, respectively.

PMID- 17519412
TI  - Improved diagnostic testing and malaria treatment practices in Zambia.
AB  - CONTEXT: Improving the accuracy of malaria diagnosis with rapid antigen-detection
      diagnostic tests (RDTs) has been proposed as an approach for reducing
      overtreatment of malaria in the current era of widespread implementation of
      artemisinin-based combination therapy in sub-Saharan Africa. OBJECTIVE: To assess
      the association between use of microscopy and RDT and the prescription of
      antimalarials. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, cluster sample
      survey, carried out between March and May 2006, of all outpatients treated during
      1 working day at government and mission health facilities in 4 sentinel districts
      in Zambia. MAIN OUTCOME MEASURE: Proportions of patients undergoing malaria
      diagnostic procedures and receiving antimalarial treatment. RESULTS: Seventeen
      percent of the 104 health facilities surveyed had functional microscopy, 63% had
      RDTs available, and 73% had 1 or more diagnostics available. Of patients with
      fever (suspected malaria), 27.8% (95% confidence interval [CI], 13.1%-42.5%)
      treated in health facilities with malaria diagnostics were tested and 44.6% had
      positive test results. Of patients with negative blood smear results, 58.4% (95%
      CI, 36.7%-80.2%) were prescribed an antimalaria drug, as were 35.5% (95% CI,
      16.0%-55.0%) of those with a negative RDT result. Of patients with fever who did
      not have diagnostic tests done, 65.9% were also prescribed antimalarials. In
      facilities with artemether-lumefantrine in stock, this antimalarial was
      prescribed to a large proportion of febrile patients with a positive diagnostic
      test result (blood smear, 75.0% [95% CI, 51.7%-98.3%]; RDT, 70.4% [95% CI, 39.3%
      100.0%]), but also to some of those with a negative diagnostic test result (blood
      smear, 30.4% [95% CI, 8.0%-52. 9%]; RDT, 26.7% [95% CI, 5.7%-47.7%]).
      CONCLUSIONS: Despite efforts to expand the provision of malaria diagnostics in
      Zambia, they continue to be underused and patients with negative test results
      frequently receive antimalarials. Provision of new tools to reduce inappropriate
      use of new expensive antimalarial treatments must be accompanied by a major
      change in clinical treatment of patients presenting with fever but lacking
      evidence of malaria infection.

PMID- 17519413
TI  - Burden, features, and outcome of neurological involvement in acute falciparum
      malaria in Kenyan children.
AB  - CONTEXT: Plasmodium falciparum appears to have a particular propensity to involve
      the brain but the burden, risk factors, and full extent of neurological
      involvement have not been systematically described. OBJECTIVES: To determine the
      incidence and describe the clinical phenotypes and outcomes of neurological
      involvement in African children with acute falciparum malaria. DESIGN, SETTING,
      AND PATIENTS: A review of records of all children younger than 14 years admitted
      to a Kenyan district hospital with malaria from January 1992 through December
      2004. Neurological involvement was defined as convulsive seizures, agitation,
      prostration, or impaired consciousness or coma. MAIN OUTCOME MEASURES: The
      incidence, pattern, and outcome of neurological involvement. RESULTS: Of 58,239
      children admitted, 19,560 (33.6%) had malaria as the primary clinical diagnosis.
      Neurological involvement was observed in 9313 children (47.6%) and manifested as
      seizures (6563/17,517 [37.5%]), agitation (316/11,193 [2.8%]), prostration
      (3223/15,643 [20.6%]), and impaired consciousness or coma (2129/16,080 [13.2%]).
      In children younger than 5 years, the mean annual incidence of admissions with
      malaria was 2694 per 100,000 persons and the incidence of malaria with
      neurological involvement was 1156 per 100,000 persons. However, readmissions may
      have led to a 10% overestimate in incidence. Children with neurological
      involvement were older (median, 26 [interquartile range {IQR}, 15-41] vs 21 [IQR,
      10-40] months; P<.001), had a shorter duration of illness (median, 2 [IQR, 1-3]
      vs 3 [IQR, 2-3] days; P<.001), and a higher geometric mean parasite density (42.0
      [95% confidence interval {CI}, 40.0-44.1] vs 30.4 [95% CI, 29.0-31.8] x
      10(3)/microL; P<.001). Factors independently associated with neurological
      involvement included past history of seizures (adjusted odds ratio [AOR], 3.50;
      95% CI, 2.78-4.42), fever lasting 2 days or less (AOR, 2.02; 95% CI, 1.64-2.49),
      delayed capillary refill time (AOR, 3.66; 95% CI, 2.40-5.56), metabolic acidosis
      (AOR, 1.55; 95% CI, 1.29-1.87), and hypoglycemia (AOR, 2.11; 95% CI, 1.31-3.37).
      Mortality was higher in patients with neurological involvement (4.4% [95% CI,
      4.2%-5.1%] vs 1.3% [95% CI, 1.1%-1.5%]; P<.001). At discharge, 159 (2.2%) of 7281
      patients had neurological deficits. CONCLUSIONS: Neurological involvement is
      common in children in Kenya with acute falciparum malaria, and is associated with
      metabolic derangements, impaired perfusion, parasitemia, and increased mortality
      and neurological sequelae. This study suggests that falciparum malaria exposes
      many African children to brain insults.

PMID- 17519414
TI  - Estimating the number of insecticide-treated nets required by African households
      to reach continent-wide malaria coverage targets.
AB  - CONTEXT: African countries are scaling up malaria interventions, especially
      insecticide-treated nets (ITNs), for which ambitious coverage targets have been
      set. OBJECTIVE: To estimate how many ITNs are available in African households
      that are at risk of malaria and how many ITNs are needed to reach targets for use
      by children younger than 5 years and pregnant women. DATA SOURCES: Primary
      sources of data were the Multiple Indicator Cluster Surveys II, the Demographic
      and Health Surveys, or other nationally representative or large-scale household
      surveys that measured household possession and use of nets or ITNs among children
      younger than 5 years. DATA EXTRACTION: Data from 42 household surveys between
      1999 and 2006 on net and ITN coverage (either household possession or use) and
      average numbers of nets and ITNs per household were compared with populations and
      households at risk. Data are included for 43 sub-Saharan African countries. DATA
      SYNTHESIS: For the median survey year 2003, the population-weighted mean
      proportion of households possessing at least 1 ITN was 6.7% (range among
      countries, 0.1%-71.0%) and was 23.8% (range, 5.0%-91.2%) for any type of net.
      Based on an average of 0.13 ITNs per household, we estimated that 53.6 million
      nets, of which 16.7 million were ITNs, were available in households at risk of
      malaria. Between 130 million and 264 million ITNs are required in 2007 to reach
      the 80% coverage target for about 133 million children younger than 5 years and
      pregnant women living in 123 million households in risk areas; the exact number
      depends on usage patterns (best estimate, assuming 55% of owned ITNs are used by
      the target groups, 192 million ITNs). CONCLUSION: To achieve the targeted ITN
      usage rates, numbers of ITNs available to African households must be dramatically
      increased.

PMID- 17519415
TI  - Controversies and misconceptions in malaria chemoprophylaxis for travelers.
AB  - CONTEXT: Controversies in malaria prevention arise from the absence of data,
      conflicting data between different studies, conflicting recommendations,
      deviation of local practice from scientific data, and varying risk thresholds.
      Misconceptions about the seriousness of malaria, the tolerability of
      chemoprophylaxis drugs, and the efficacy and safety of repellents contribute to
      the controversies. OBJECTIVES: To compare several national guidelines on malaria
      chemoprophylaxis to identify variations in recommendations. We reviewed studies
      on tolerability of mefloquine with particular focus on its neuropsychiatric
      adverse effects and influence on performance. We also describe why most
      recommended chemoprophylactic regimens fail to prevent relapses of Plasmodium
      vivax malaria and review available options. EVIDENCE ACQUISITION: We searched
      scientific publications in MEDLINE via PubMED for relevant articles with a cutoff
      date of December 2006 using the search terms malaria, chemoprophylaxis, travel,
      mefloquine, neuropsychiatric adverse events, tolerability, vivax malaria, and
      primaquine. Additional references were obtained from bibliographies of the
      selected articles. There were no language restrictions. EVIDENCE SYNTHESIS: Gaps
      and conflicts exist among current guidelines. Health authorities vary in the
      chemoprophylaxis drugs they recommend, the indications for continuous prophylaxis
      vs no prophylaxis, and the use of standby emergency treatment. Despite widespread
      reports on the adverse effects of mefloquine, controlled studies found that
      serious neuropsychiatric adverse events occur at rates comparable with or lower
      than other chemoprophylaxis drugs. Moreover, mefloquine does not appear to impair
      performance while driving, flying, or diving. Vivax malaria causes significant
      illness in travelers, but current first-line chemoprophylaxis agents do not
      prevent relapses of vivax malaria. Although not licensed in most countries as
      primary prophylaxis, primaquine effectively prevents relapses of vivax malaria.
      CONCLUSIONS: Prevention of malaria in travelers requires detailed knowledge of
      malaria epidemiology and host-vector-parasite interactions. Decisions are
      complicated by a lack of standardized recommendations, controversies, and
      misconceptions. Improved international consensus is indicated to minimize
      conflicting guidelines, clarify controversies, and promote adherence to
      preventive measures.

PMID- 17519416
TI  - Treatment of malaria in the United States: a systematic review.
AB  - CONTEXT: Many US clinicians and laboratory personnel are unfamiliar with the
      diagnosis and treatment of malaria. OBJECTIVES: To examine the evidence base for
      management of uncomplicated and severe malaria and to provide clinicians with
      practical recommendations for the diagnosis and treatment of malaria in the
      United States. EVIDENCE ACQUISITION: Systematic MEDLINE search from 1966 to 2006
      using the search term malaria (with the subheadings congenital, diagnosis, drug
      therapy, epidemiology, and therapy). Additional references were obtained from
      searching the bibliographies of pertinent articles and by reviewing articles
      suggested by experts in the treatment of malaria in North America. EVIDENCE
      SYNTHESIS: Important measures to reduce morbidity and mortality from malaria in
      the United States include the following: obtaining a travel history, considering
      malaria in the differential diagnosis of fever based on the travel history, and
      prompt and accurate diagnosis and treatment. Chloroquine remains the treatment of
      choice for Plasmodium falciparum acquired in areas without chloroquine-resistant
      strains. In areas with chloroquine resistance, a combination of atovaquone and
      proguanil or quinine plus tetracycline or doxycycline or clindamycin are the best
      treatment options. Chloroquine remains the treatment of choice for all other
      malaria species, with the exception of P vivax acquired in Indonesia or Papua New
      Guinea, in which case atovaquone-proguanil is best, with mefloquine or quinine
      plus tetracycline or doxycycline as alternatives. Quinidine is currently the
      recommended treatment for severe malaria in the United States because the
      artemisinins are not yet available. Severe malaria occurs when a patient with
      asexual malaria parasitemia, and no other confirmed cause of symptoms, has 1 or
      more designated clinical or laboratory findings. The only adjunctive measure
      recommended in severe malaria is exchange transfusion. CONCLUSIONS: Malaria
      remains a diagnostic and treatment challenge for US clinicians as increasing
      numbers of persons travel to and emigrate from malarious areas. A strong evidence
      base exists to help clinicians rapidly initiate appropriate therapy and minimize
      the major mortality and morbidity burdens caused by this disease.

PMID- 17519417
TI  - Global malaria control in the 21st century: a historic but fleeting opportunity.

PMID- 17519418
TI  - Malaria 2007--progressing research, persisting challenges.

PMID- 17519420
TI  - JAMA patient page. Malaria.

PMID- 17519421
TI  - Variation in TCF7L2 influences therapeutic response to sulfonylureas: a GoDARTs
      study.
AB  - OBJECTIVE: There is considerable interindividual variation in sulfonylurea
      response in type 2 diabetes. Transcription factor 7-like 2 (TCF7L2) variants have
      been identified to be strongly associated with type 2 diabetes risk, probably due
      to decreased beta-cell function. We hypothesized that variation in TCF7L2 would
      influence response to sulfonylureas but not metformin. We studied the effect of
      TCF7L2 rs12255372 and rs7903146 genotypes on glycemic response. RESEARCH DESIGN
      AND METHODS: The DARTS/MEMO (Diabetes Audit and Research Tayside/Medicines
      Monitoring Unit) collaboration database includes prescribing, biochemistry, and
      clinical phenotype of all patients with diabetes within Tayside, Scotland, from
      1992. Of these, the TCF7L2 genotype was determined in 4,469 patients with type 2
      diabetes recruited to GoDARTS (Genetics of Diabetes Audit and Research Tayside)
      between 1997 and July 2006. A total of 901 incident sulfonylurea users and 945
      metformin users were identified. A logistic regression was used with treatment
      failure defined as an A1C >7% within 3-12 months after treatment initiation.
      Covariates included the TCF7L2 genotype, BMI, sex, age diagnosed, drug adherence,
      and drug dose. A1C pretreatment was available in a subset of patients
      (sulfonylurea n = 579; metformin n = 755). RESULTS: Carriers of the risk allele
      were less likely to respond to sulfonylureas with an odds ratio (OR) for failure
      of 1.95 (95% CI 1.23-3.06; P = 0.005), comparing rs12255372 T/T vs. G/G.
      Including the baseline A1C strengthened this association (OR 2.16 [95% CI 1.21
      3.86], P = 0.009). A similar, although slightly weaker, association was seen with
      rs7903146. No association was seen between metformin response and either single
      nucleotide polymorphism, after adjustment for baseline A1C. CONCLUSIONS: TCF7L2
      variants influence therapeutic response to sulfonylureas but not metformin. This
      study establishes that genetic variation can alter response to therapy in type 2
      diabetes.

PMID- 17519422
TI  - Excess lipid availability increases mitochondrial fatty acid oxidative capacity
      in muscle: evidence against a role for reduced fatty acid oxidation in lipid
      induced insulin resistance in rodents.
AB  - A reduced capacity for mitochondrial fatty acid oxidation in skeletal muscle has
      been proposed as a major factor leading to the accumulation of intramuscular
      lipids and their subsequent deleterious effects on insulin action. Here, we
      examine markers of mitochondrial fatty acid oxidative capacity in rodent models
      of insulin resistance associated with an oversupply of lipids. C57BL/6J mice were
      fed a high-fat diet for either 5 or 20 weeks. Several markers of muscle
      mitochondrial fatty acid oxidative capacity were measured, including (14)C
      palmitate oxidation, palmitoyl-CoA oxidation in isolated mitochondria, oxidative
      enzyme activity (citrate synthase, beta-hydroxyacyl CoA dehydrogenase, medium
      chain acyl-CoA dehydrogenase, and carnitine palmitoyl-transferase 1), and
      expression of proteins involved in mitochondrial metabolism. Enzyme activity and
      mitochondrial protein expression were also examined in muscle from other rodent
      models of insulin resistance. Compared with standard diet-fed controls, muscle
      from fat-fed mice displayed elevated palmitate oxidation rate (5 weeks +23%, P <
      0.05, and 20 weeks +29%, P < 0.05) and increased palmitoyl-CoA oxidation in
      isolated mitochondria (20 weeks +49%, P < 0.01). Furthermore, oxidative enzyme
      activity and protein expression of peroxisome proliferator-activated receptor
      gamma coactivator (PGC)-1alpha, uncoupling protein (UCP) 3, and mitochondrial
      respiratory chain subunits were significantly elevated in fat-fed animals. A
      similar pattern was present in muscle of fat-fed rats, obese Zucker rats, and
      db/db mice, with increases observed for oxidative enzyme activity and expression
      of PGC-1alpha, UCP3, and subunits of the mitochondrial respiratory chain. These
      findings suggest that high lipid availability does not lead to intramuscular
      lipid accumulation and insulin resistance in rodents by decreasing muscle
      mitochondrial fatty acid oxidative capacity.

PMID- 17519423
TI  - Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity
      and insulin resistance.
AB  - Obesity is associated with insulin resistance and a state of abnormal
      inflammatory response. The Toll-like receptor (TLR)4 has an important role in
      inflammation and immunity, and its expression has been reported in most tissues
      of the body, including the insulin-sensitive ones. Because it is activated by
      lipopolysaccharide and saturated fatty acids, which are inducers of insulin
      resistance, TLR4 may be a candidate for participation in the cross-talk between
      inflammatory and metabolic signals. Here, we show that C3H/HeJ mice, which have a
      loss-of-function mutation in TLR4, are protected against the development of diet
      induced obesity. In addition, these mice demonstrate decreased adiposity,
      increased oxygen consumption, a decreased respiratory exchange ratio, improved
      insulin sensitivity, and enhanced insulin-signaling capacity in adipose tissue,
      muscle, and liver compared with control mice during high-fat feeding. Moreover,
      in these tissues, control mice fed a high-fat diet show an increase in IkappaB
      kinase complex and c-Jun NH(2)-terminal kinase activity, which is prevented in
      C3H/HeJ mice. In isolated muscles from C3H/HeJ mice, protection from saturated
      fatty acid-induced insulin resistance is observed. Thus, TLR4 appears to be an
      important mediator of obesity and insulin resistance and a potential target for
      the therapy of these highly prevalent medical conditions.

PMID- 17519424
TI  - Micromanagement during the innate immune response.
AB  - The innate immune response can be initiated by the binding of various pathogen
      associated compounds or cytokines to receptors on the surfaces of dendritic
      cells. These interactions result in the activation of many genes and gene
      products. Several different pathways converge to raise the abundance of specific
      microRNAs (miRNAs). In particular, activation of the transcription factors AP-1
      and NF-kappaB results in an increase in the amount of miR-155. High levels of
      this miRNA are associated with several types of cancer. However, the mRNAs that
      may be targeted by miR-155 in the innate immune response remain to be determined.

PMID- 17519426
TI  - Health care affordability and complementary and alternative medicine utilization
      by adults with diabetes.

PMID- 17519427
TI  - Childhood obesity and metabolic imprinting: the ongoing effects of maternal
      hyperglycemia.
AB  - OBJECTIVE: The purpose of this study was to determine how the range of measured
      maternal glycemia in pregnancy relates to risk of obesity in childhood. RESEARCH
      DESIGN AND METHODS: Universal gestational diabetes mellitus (GDM) screening (a 50
      g glucose challenge test [GCT]) was performed in two regions (Northwest and
      Hawaii) of a large diverse HMO during 1995-2000, and GDM was diagnosed/treated
      using a 3-h 100-g oral glucose tolerance test (OGTT) and National Diabetes Data
      Group (NDDG) criteria. Measured weight in offspring (n = 9,439) was ascertained 5
      7 years later to calculate sex-specific weight-for-age percentiles using U.S.
      norms (1963-1994 standard) and then classified by maternal positive GCT (1 h >or=
      7.8 mmol/l) and OGTT results (1 or >or=2 of the 4 time points abnormal: fasting,
      1 h, 2 h, or 3 h by Carpenter and Coustan and NDDG criteria). RESULTS: There was
      a positive trend for increasing childhood obesity at age 5-7 years (P < 0.0001;
      85th and 95th percentiles) across the range of increasing maternal glucose screen
      values, which remained after adjustment for potential confounders including
      maternal weight gain, maternal age, parity, ethnicity, and birth weight. The risk
      of childhood obesity in offspring of mothers with GDM by NDDG criteria (treated)
      was attenuated compared with the risks for the groups with lesser degrees of
      hyperglycemia (untreated). The relationships were similar among Caucasians and
      non-Caucasians. Stratification by birth weight also revealed these effects in
      children of normal birth weight (<or=4,000 g). CONCLUSIONS: Our results in a
      multiethnic U.S. population suggest that increasing hyperglycemia in pregnancy is
      associated with an increased risk of childhood obesity. More research is needed
      to determine whether treatment of GDM may be a modifiable risk factor for
      childhood obesity.

PMID- 17519428
TI  - Scottish foot ulcer risk score predicts foot ulcer healing in a regional
      specialist foot clinic.
AB  - OBJECTIVE: To determine whether patients developing ulcers had previously been
      identified as being at high risk of ulceration using the Scottish Care
      Information-Diabetes Collaboration (SCI-DC) ulcer risk score and whether the risk
      score predicts ulcer healing. RESEARCH DESIGN AND METHODS: All patients attending
      the diabetes foot clinic with an ulcer had been assessed for foot ulcer risk
      using the SCI-DC risk calculator, which categorizes patients into low, moderate,
      or high risk of ulceration. Information on foot pulses, neuropathy, foot
      deformity, previous ulcer, ulcer site, depth, and presence of sepsis was recorded
      and related to ulcer outcome. Patients were followed up until outcome was
      achieved (median 3 months [range 1-33]). RESULTS: Of patients attending the
      clinic with a foot ulcer (mean [+/-SD] age 67.3 +/- 12.7 years, 68% male), 68%
      were previously recognized to be at high risk of foot ulceration, and 98% were
      high or moderate risk. Of 221 ulcers, the healing rate was 75% overall but was
      lower for high-risk patients compared with other patients (68 vs. 93%; P <
      0.0001). Of the remainder, 3% became chronic ulcers, 12% required minor or major
      amputation, and 10% died with their ulcer. In multivariate analysis, absent
      pulses, neuropathy, increased age, and deep ulcers were associated with poor
      healing. The combination of neuropathy and ischemia was particularly associated
      with poor outcome of an ulcer (61% healing). CONCLUSIONS: The Scottish foot ulcer
      risk score predicts both ulcer development and ulcer healing. The risk score can
      be a useful initial guide to determine the likelihood of poor healing. The
      individual criteria contributing to this overall risk are similar to other
      studies.

PMID- 17519429
TI  - Combining population health and baseline risk strategy by determining an age
      cutoff for initiating statins in patients with diabetes: a population-based
      study.
AB  - OBJECTIVE: Strategies for initiating statin use among adult patients with
      diabetes for primary cardiovascular disease (CVD) prevention include treating all
      patients (assuming diabetes is a coronary risk equivalent) or treating patients
      who are at risk of developing CVD. The aim of the study was to combine both
      strategies to derive an appropriate age cutoff for prescribing statins. By
      considering different strategies, we also aim to assess the effectiveness and
      efficiency of different strategies to reduce CVD events. RESEARCH DESIGN AND
      METHODS: This was a cross-sectional primary care population study using
      electronic patient files from 304 general practitioner practices in England and
      Wales. Of 60,258 patients with diabetes, 11,005 men and women aged 30-74 years
      fullfilled criteria for primary CVD prevention. Model outcomes were extrapolated
      to an estimated national diabetes prevalence of 3.6%. RESULTS: The age transition
      from a low-risk to a moderate-risk category for diabetic men and women occurred
      at ages 40.6 and 44.2 years, respectively, and sensitivity and specificity for
      fulfilling moderate CVD risk criteria were 97.9 and 61.8% for men and 92.0 and
      77.0% for women. When applied to the national population, the age cutoff
      strategies were an effective and efficient strategy, potentially avoiding 11,094
      events with a number needed to treat of 25.1. CONCLUSIONS: A strategy to treat
      all men and women with diabetes aged >40 and 45 years, respectively, with statins
      showed good compromise between high effectiveness and high efficiency for
      reducing CVD events. Strategy to intervene if cholesterol was >5 mmol/l was the
      least effective and efficient in preventing CVD events.

PMID- 17519430
TI  - Nonalcoholic fatty liver disease is independently associated with an increased
      incidence of cardiovascular events in type 2 diabetic patients.

PMID- 17519431
TI  - The prevalence of cutaneous manifestations in young patients with type 1
      diabetes.
AB  - OBJECTIVE: The aim of the study was to assess the prevalence of cutaneous
      disorders and their relation to disease duration, metabolic control, and
      microvascular complications in children and adolescents with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: The presence and frequency of skin manifestations
      were examined and compared in 212 unselected type 1 diabetic patients (aged 2-22
      years, diabetes duration 1-15 years) and 196 healthy sex- and age-matched control
      subjects. Logistic regression was used to analyze the relation of cutaneous
      disorders with diabetes duration, glycemic control, and microvascular
      complications. RESULTS: One hundred forty-two (68%) type 1 diabetic patients had
      at least one cutaneous disorder vs. 52 (26.5%) control subjects (P < 0.01).
      Diabetes-associated skin lesions were found in 81 (38%) patients. Acquired
      ichthyosis, rubeosis faciei, diabetic hand, and necrobiosis lipoidica were seen
      in 22 vs. 3%, 7.1 vs. 0%, 2.3 vs. 0%, and 2.3 vs. 0% of type 1 diabetic and
      control subjects, respectively. The frequency of cutaneous reactions to insulin
      therapy was low (-2.7%). The prevalence of fungal infections in patients and
      control subjects was 4.7% and 1.5%, respectively. Keratosis pilaris affected 12%
      of our patients vs. 1.5% of control subjects. Diabetic hand was strongly (odds
      ratio 1.42 [95% CI 1.11-1.81]; P < 0.001), and rubeosis faciei weakly (1.22 [1.04
      1.43]; P = 0.0087), associated with diabetes duration. Significant association
      was also found between acquired ichthyosis and keratosis pilaris (1.53 [1.09
      1.79]; P < 0.001). CONCLUSIONS: Cutaneous manifestations are common in type 1
      diabetic patients, and some of them, like acquired ichthyosis and keratosis
      pilaris, develop early in the course of the disease. Diabetic hand and rubeosis
      faciei are related to disease duration.

PMID- 17519432
TI  - A longitudinal study of lipids and blood pressure in relation to method of
      contraception in Latino women with prior gestational diabetes mellitus.
AB  - OBJECTIVE: To investigate the effect of nonhormonal contraception (NHC),
      combination oral contraception (COC), and depo-medroxyprogesterone acetate (DMPA)
      on lipids and blood pressure in women with recent gestational diabetes mellitus
      (GDM). RESEARCH DESIGN AND METHODS: An observational cohort of 972 nondiabetic,
      normotensive, postpartum Latino women who elected NHC (n = 448), COC (n = 430),
      or DMPA (n = 94) were followed for at least one subsequent metabolic evaluation
      on the same contraception. Baseline and follow-up measures included glucose
      tolerance testing, fasting serum LDL and HDL cholesterol, triglycerides, and
      systolic (SBP) and diastolic (DBP) blood pressure. Patterns of changes in lipids
      and blood pressure were evaluated by comparing slopes over follow-up time using
      random coefficient linear mixed-effects models. RESULTS: Median follow-up times
      were 20, 12, and 11 months in the NHC, COC, and DMPA groups. The DMPA users
      gained significantly more weight (4.3 +/- 6.9 kg/year) compared with NHC and COC
      users (1.2 +/- 4.7 and 0.7 +/- 6.0 kg/year, respectively; P < 0.0001). Patterns
      of change in LDL cholesterol, triglycerides, and DBP were not significantly
      different among groups. HDL cholesterol change differed only between COC and NHC
      groups (adjusted slopes: 1.0 vs. -1.6 mg x dl(-1) x year(-1), respectively; P <
      0.0001). SBP change differed only between COC and DMPA groups (adjusted slopes:
      1.3 vs. -1.7 mmHg/year, respectively; P = 0.01). CONCLUSIONS: These results,
      derived predominantly from the initial 1-2 years of treatment in Hispanic women,
      demonstrate that DMPA was associated with greater weight gain than NHCs or COCs.
      Other differences in blood pressure and lipid effects were very small. These
      findings should be taken into account when advising women with recent GDM about
      their contraceptive choices.

PMID- 17519433
TI  - Presence of GAD antibodies during gestational diabetes mellitus predicts type 1
      diabetes.
AB  - OBJECTIVE: We sought to study the frequency of beta-cell-specific autoantibody
      markers in women with gestational diabetes mellitus (GDM) and to follow these
      women to estimate the risk of later development of type 1 diabetes. RESEARCH
      DESIGN AND METHODS: Of 385 pregnant women with GDM during 1995-2005 in the
      district of Lund, 24 (6%) women were found positive for at least one of the
      following: islet cell antibody (ICA), GAD antibody (GADA), or tyrosine
      phosphatase antibody (IA-2A). The women were followed and autoantibodies
      reanalyzed. Those who had not developed diabetes did an oral glucose tolerance
      test. The frequencies of known risk factors for GDM were compared in women with
      GDM with and without pancreatic autoantibodies. RESULTS: Among the autoantibody
      positive women, 50% had developed type 1 diabetes compared with none among the
      GDM control subjects (P = 0.001), 21% had impaired fasting glucose or impaired
      glucose tolerance compared with 12.5% among control subjects (P = 0.3), and none
      had developed type 2 diabetes compared with 12.5% among control subjects (P =
      0.1). CONCLUSIONS: Autoantibody screening in pregnant women with GDM and follow
      up after delivery should be considered for early recognition of type 1 diabetes.

PMID- 17519434
TI  - Is waist circumference an essential component of the metabolic syndrome?

PMID- 17519435
TI  - Folic acid does not improve endothelial function in obese children and
      adolescents.
AB  - OBJECTIVE: Obese children have severe endothelial dysfunction as measured by flow
      mediated dilation (FMD). We have shown that folic acid normalizes endothelial
      function in children with type 1 diabetes who have a similar degree of
      endothelial dysfunction but lower total plasma homocyst(e)ine (tHcy) and higher
      folate status. Our aim was to evaluate, for the first time, the effect of folate
      supplementation on endothelial dysfunction in obese children. RESEARCH DESIGN AND
      METHODS: A total of 53 obese subjects (26 male, mean +/- SD age 13.3 +/- 2.2
      years, and BMI Z score 2.29 +/- 0.25) participated in a randomized, double-blind,
      placebo-controlled, parallel trial of oral folic acid (5 mg/day) or placebo for 8
      weeks. Before and after the intervention, we assessed endothelial function (FMD),
      smooth muscle function (glyceryl trinitrate-induced dilatation [GTN]), high
      sensitivity C-reactive protein (hsCRP), tHcy, serum folate, red cell folate
      (RCF), and lipids. RESULTS: There were no group differences at baseline. FMD did
      not change with the intervention (folic acid group pre- and postintervention:
      6.42 +/- 5.03 and 6.56 +/- 4.79%, respectively, vs. placebo group: 5.17 +/- 3.54
      and 5.79 +/- 4.26%, respectively; P = 0.6). Folate supplementation increased
      serum folate and RCF by 18.4 nmol/l (P < 0.001) and 240.1 nmol/l (P < 0.001),
      respectively, and decreased tHcy by 0.95 microl (P = 0.008). The intervention did
      not change GTN, hsCRP, or lipids. CONCLUSIONS: Folic acid supplementation does
      not improve endothelial function in obese children without diabetes despite
      increasing folate status and reducing tHcy. This is in contrast to the response
      to folate in children with type 1 diabetes.

PMID- 17519436
TI  - Effect of chromium supplementation on glucose metabolism and lipids: a systematic
      review of randomized controlled trials.
AB  - OBJECTIVE: A systematic review of the effect of chromium supplementation on
      glucose metabolism and lipid levels. RESEARCH DESIGN AND METHODS: A literature
      search was conducted in MEDLINE and the Commonwealth Agricultural Bureau.
      Eligible studies were English language randomized controlled trials of chromium
      supplement intake > or = 3 weeks, with > or = 10 participants receiving chromium.
      All trials with glucose metabolism outcomes and trials of individuals with
      diabetes or glucose intolerance for lipid outcomes were included. Meta-analyses
      were performed as appropriate. RESULTS: Forty-one studies met criteria, almost
      half of which were of poor quality. Among participants with type 2 diabetes,
      chromium supplementation improved glycosylated hemoglobin levels by -0.6% (95% CI
      -0.9 to -0.2) and fasting glucose by -1.0 mmol/l (-1.4 to -0.5) but not lipids.
      There was no benefit in individuals without diabetes. There were some indications
      of dose effect and differences among chromium formulations. Larger effects were
      more commonly observed in poor-quality studies. The evidence was limited by poor
      study quality, heterogeneity in methodology and results, and a lack of consensus
      on assessment of chromium status. CONCLUSIONS: No significant effect of chromium
      on lipid or glucose metabolism was found in people without diabetes. Chromium
      supplementation significantly improved glycemia among patients with diabetes.
      However, future studies that address the limitations in the current evidence are
      needed before definitive claims can be made about the effect of chromium
      supplementation.

PMID- 17519437
TI  - Genome sequence of a proteolytic (Group I) Clostridium botulinum strain Hall A
      and comparative analysis of the clostridial genomes.
AB  - Clostridium botulinum is a heterogeneous Gram-positive species that comprises
      four genetically and physiologically distinct groups of bacteria that share the
      ability to produce botulinum neurotoxin, the most poisonous toxin known to man,
      and the causative agent of botulism, a severe disease of humans and animals. We
      report here the complete genome sequence of a representative of Group I
      (proteolytic) C. botulinum (strain Hall A, ATCC 3502). The genome consists of a
      chromosome (3,886,916 bp) and a plasmid (16,344 bp), which carry 3650 and 19
      predicted genes, respectively. Consistent with the proteolytic phenotype of this
      strain, the genome harbors a large number of genes encoding secreted proteases
      and enzymes involved in uptake and metabolism of amino acids. The genome also
      reveals a hitherto unknown ability of C. botulinum to degrade chitin. There is a
      significant lack of recently acquired DNA, indicating a stable genomic content,
      in strong contrast to the fluid genome of Clostridium difficile, which can form
      longer-term relationships with its host. Overall, the genome indicates that C.
      botulinum is adapted to a saprophytic lifestyle both in soil and aquatic
      environments. This pathogen relies on its toxin to rapidly kill a wide range of
      prey species, and to gain access to nutrient sources, it releases a large number
      of extracellular enzymes to soften and destroy rotting or decayed tissues.

PMID- 17519438
TI  - Gender differences in anterior cruciate ligament injury vary with activity:
      epidemiology of anterior cruciate ligament injuries in a young, athletic
      population.
AB  - BACKGROUND: Previous studies have shown that women involved in similar activities
      as men are at increased risk for anterior cruciate ligament injuries. HYPOTHESIS:
      The incidence rate of complete anterior cruciate ligament tears for men and women
      in our athletic, college-aged population is similar. STUDY DESIGN: Descriptive
      epidemiology study. METHODS: Students graduating in class years 1994 to 2003 at
      our institution who sustained complete anterior cruciate ligament tears were
      assessed for mechanism of injury and type of sport played at time of injury. We
      calculated the incidence proportion, an estimation of risk, by gender and class
      year, and the incidence proportion ratio comparing men and women by class year.
      We also calculated incidence rates by gender and type of sport played and
      incidence rate ratios comparing men and women. RESULTS: There were 353 anterior
      cruciate ligament injuries in the 10 classes studied. We found an overall, 4-year
      incidence proportion of 3.24 per 100 (95% confidence interval, 2.89-3.63) for men
      and 3.51 (95% confidence interval, 2.65-4.65) for women (incidence proportion
      ratio, 1.09 [95% confidence interval, 0.80-1.47]). The overall anterior cruciate
      ligament injury rate, excluding male-only sports, was significantly greater in
      women (incidence rate ratio, 1.51 [95% confidence interval, 1.03-2.21]). We found
      significantly greater injury rates among women in a gymnastics course (incidence
      rate ratio, 5.67 [95% confidence interval, 1.99-16.16]), indoor obstacle course
      test (incidence rate ratio, 3.72 [95% confidence interval, 1.25-11.10]), and
      basketball (incidence rate ratio, 2.42 [95% confidence interval, 1.05-5.59]).
      CONCLUSION: We found little gender difference in the overall risk of an anterior
      cruciate ligament tear; however, there were gender differences in injury rates
      when specific sports and activities were compared and when male-only sports were
      removed from the overall rate assessment.

PMID- 17519439
TI  - Syndesmotic ankle sprains in athletes.
AB  - Ankle sprains are among the most common athletic injuries and represent a
      significant source of persistent pain and disability. Despite the high incidence
      of ankle sprains in athletes, syndesmosis injuries have historically been
      underdiagnosed, and assessment in terms of severity and optimal treatment has not
      been determined. More recently, a heightened awareness in sports medicine has
      resulted in more frequent diagnoses of syndesmosis injuries. However, there is a
      low level of evidence and a paucity of literature on this topic compared with
      lateral ankle sprains. As a result, no clear guidelines are available to help the
      clinician assess the severity of injury, choose an imaging modality to visualize
      the injury, make a decision in terms of operative versus nonoperative treatment,
      or decide when the athlete may return to play. Increased knowledge and
      understanding of these injuries by clinicians and researchers are essential to
      improve the prevention, diagnosis, and treatment of this significant condition.
      This review will discuss the anatomy, mechanism of injury, diagnosis, and
      treatment of syndesmosis sprains of the ankle while identifying controversies in
      management and topics for future research.

PMID- 17519440
TI  - Arthroscopic capsulolabral reconstruction of the type VIII superior labrum
      anterior posterior lesion: mean 2-year follow-up on 13 shoulders.
AB  - BACKGROUND: A type VIII superior labrum anterior posterior lesion represents
      pathologic posteroinferior extension of a type II superior labrum anterior
      posterior lesion with injury to the insertion of the posterior band of the
      inferior glenohumeral ligament. No reports in the literature describe
      arthroscopic treatment of a type VIII superior labrum anterior posterior lesion
      and its associated glenohumeral instability. HYPOTHESIS: Arthroscopic
      capsulolabral reconstruction is effective in alleviating pain and restoring
      stability and function in athletes with glenohumeral instability due to the type
      VIII superior labrum anterior posterior lesion. STUDY DESIGN: Case series; Level
      of evidence, 4. METHODS: From 2003 to 2006, 23 shoulders in 23 athletes were
      diagnosed with a type VIII superior labrum anterior posterior lesion by physical
      examination, magnetic resonance arthrography, and arthroscopy. All were treated
      with an arthroscopic capsulolabral reconstruction. Ten patients were involved in
      rehabilitation less than 9 months after surgery and were not included in this
      study. Thirteen remaining shoulders in 13 athletes with a mean age of 27.8 +/-
      10.9 years were analyzed at a mean follow-up of 24 months. Shoulders were
      evaluated preoperatively and postoperatively using the American Shoulder and
      Elbow Surgeons scoring system and standard subjective scales for stability,
      strength, function, and range of motion. RESULTS: Athletes most commonly
      participated in sport at the recreational level (n = 8), followed by collegiate
      (n = 3) and high school (n = 2). The most common activity was weight lifting (n =
      4). Eight athletes (62%) participated in contact sports, most commonly football
      and wrestling. Two patients (15%) had a partial-thickness articular-sided
      supraspinatus tendon tear that was debrided at the time of surgery. Mean American
      Shoulder and Elbow Surgeons score improved from 51.4 to 90.0 (P < .001). There
      were significant improvements in stability, pain, function, and range of motion
      based on standardized subjective scales (P < .001). No shoulder required revision
      surgery for recurrent instability. All patients were able to return to sports,
      with 9 (69%) able to return to their highest level before surgery. CONCLUSION:
      Arthroscopic capsulolabral reconstruction is an effective and reliable treatment
      for glenohumeral instability due to a type VIII superior labrum anterior
      posterior lesion in the contact, noncontact, and throwing athlete. Successful
      postoperative return to sport is a reasonable expectation.

PMID- 17519441
TI  - Managing acute coronary syndrome: evidence-based approaches.
AB  - PURPOSE: To describe data and insights from a national quality improvement
      initiative known as Can Rapid Risk Stratification of Unstable Angina Patients
      Suppress Adverse Outcomes with Early Implementation of the American College of
      Cardiology (ACC)/American Heart Association (AHA) Guidelines (CRUSADE), for
      managing non-ST-segment elevation acute coronary syndrome (ACS), as well as the
      findings and implications of Acute Catheterization and Urgent Intervention Triage
      Strategy (ACUITY), a study of bivalirudin with or without a glycoprotein (GP)
      IIb/IIIa inhibitor in patients with non-ST-segment elevation ACS who were
      undergoing an invasive intervention, and the results of two recent studies of
      clopidogrel in patients with ST-segment elevation myocardial infarction (MI) that
      are not reflected in current ACC/AHA guidelines for managing ST-segment elevation
      MI. SUMMARY: Data from the CRUSADE registry suggest that there is room for
      improvement in the use of GP IIb/IIIa inhibitors and clopidogrel during the first
      24 hours of hospitalization in patients with non-ST-segment elevation ACS who
      undergo early invasive cardiac procedures, and in the prescribing of angiotensin
      converting-enzyme (ACE) inhibitors at the time of discharge. Adherence to ACC/AHA
      guidelines for non-ST-segment elevation ACS has improved over time but further
      improvement is needed. Failure to reduce the dose of a GP IIb/IIIa for patients
      with renal insufficiency resulting in excessive dosing of GP IIb/IIIa inhibitors
      increases the risk of major bleeding and is particularly common among the
      elderly, women, and patients with renal insufficiency. The ACUITY study suggests
      that bivalirudin plus a GP IIb/IIIa inhibitor is a suitable alternative to
      standard therapy for moderate- to high-risk patients with non-ST-segment
      elevation ACS who are undergoing early invasive intervention, and bivalirudin
      alone may be preferred because of a lower risk of major bleeding. However,
      interpretation of the ACUITY results is complicated by numerous methodologic
      concerns, so the role of bivalirudin in managing non-ST-segment elevation ACS is
      still evolving. In patients with ST-segment elevation, clopidogrel provides an
      early benefit in reopening occluded coronary arteries and a late benefit in
      reducing cardiovascular mortality and morbidity without increasing the risk of
      bleeding. Clopidogrel treatment is warranted before as well as after percutaneous
      coronary intervention in patients with ST-segment elevation MI who receive
      fibrinolytic therapy. Adding clopidogrel to fibrinolytic therapy and other
      standard therapy reduces mortality without increasing the risk of bleeding.
      CONCLUSION: Evidence-based guidelines provide recommendations for the management
      of ACS, but the pace of clinical research is rapid and current guidelines do not
      reflect the latest research findings. Pharmacists need to stay abreast of new
      developments and ensure that clinical practice reflects these developments.

PMID- 17519443
TI  - Translating evidence-based guidelines into performance measures for venous
      thromboembolism and acute coronary syndrome.
AB  - PURPOSE: The evolution of evidence-based quality measures in healthcare, specific
      performance measures that have been developed by various groups for the
      prevention and treatment of venous thromboembolism (VTE), the objectives and
      potential benefits of a national quality improvement initiative designed to
      improve the care of high-risk patients with acute coronary syndrome (ACS), the
      reporting of performance data to the public to guide consumer choice, and the
      recent growth in pay-for-performance programs are described. SUMMARY: Efforts to
      develop evidence-based quality measures began in the mid to late 1990s and have
      led to the creation of various safe practices, indicators, standards, and quality
      measures and initiatives. The prevention and treatment of VTE and the management
      of ACS have been the focus of some of these initiatives. Reporting of data for
      two surgery-related VTE process measures to the Centers for Medicare and Medicaid
      Services began January 1, 2007, and two additional measures may be used in the
      future. The Joint Commission and National Quality Forum have proposed eight core
      measures for the prevention and care of VTE that could eventually be used in
      hospital accreditation decisions. A national quality improvement initiative,
      CRUSADE, provides participating hospitals with feedback about performance in
      caring for high-risk patients with non-ST-segment elevation ACS. Reporting of
      performance data to the public facilitates healthcare decision making by
      consumers. The use of pay-for-performance programs that provide incentives and
      rewards for meeting quality goals has grown rapidly in recent years. CONCLUSION:
      The various initiatives under way using evidence-based performance measures to
      evaluate quality of care for VTE and ACS have the potential to improve patient
      outcomes.

PMID- 17519445
TI  - Assessing, preventing, and treating venous thromboembolism: evidence-based
      approaches.
AB  - PURPOSE: The long-term complications of deep vein thrombosis (DVT), assessment of
      risk for venous thromboembolism (VTE) in medical and surgical patients,
      recommendations in evidence-based guidelines for VTE prophylaxis in surgical and
      medical patients and the treatment of VTE, and a new alternative for VTE
      prophylaxis and treatment are discussed. SUMMARY: Pulmonary embolism (PE) is an
      acute complication of DVT, and recurrent DVT, post-thrombotic syndrome, and death
      are long-term complications of DVT. The need to assess VTE risk and provide VTE
      prophylaxis are well recognized in surgical patients. However, VTE prophylaxis is
      underutilized in medical patients despite the fact that DVT is common and
      guidelines for prophylaxis are available, partly because the condition often is
      asymptomatic in these patients. The risk for VTE increases as the number of risk
      factors increases, so the aggressiveness of VTE prophylaxis in medical and
      surgical patients increases as the risk of VTE increases. The most recent
      American College of Chest Physicians (ACCP) guidelines recommend low-dose
      unfractionated heparin or low-molecular-weight heparin (LMWH) for VTE prophylaxis
      in acutely ill medical patients. The treatment of VTE recommended by ACCP
      involves short-term LMWH or unfractionated heparin therapy plus long-term oral
      warfarin therapy. The pentasaccharide, factor Xa inhibitor, fondaparinux is a new
      alternative for VTE prophylaxis and treatment. Reducing LMWH doses for patients
      with severe renal impairment may offer a safety advantage. Fixed doses of LMWH
      are customarily used for VTE prophylaxis regardless of body weight or body mass
      index, but weight-based dosing with larger doses for obese patients may be more
      effective than fixed doses. CONCLUSION: Efforts to assess VTE risk and apply
      evidence-based guidelines for VTE prophylaxis and treatment in medical patients
      as well as surgical patients can improve patient care and outcomes. Findings from
      recent clinical research provide clinicians with clarification about the optimal
      prophylactic and treatment strategies, and future guidelines will reflect these
      findings.

PMID- 17519446
TI  - FDA mulls over paperless labeling.

PMID- 17519447
TI  - Joint Commission reverses course. Prospective, not retrospective, reviews of ED
      orders wanted.

PMID- 17519448
TI  - Katrina's aftermath expands Xavier students' clinical options.

PMID- 17519449
TI  - Pharmacist leads new security office.

PMID- 17519450
TI  - Misinformation about emergency contraception.

PMID- 17519452
TI  - Remembering Jere Goyan.

PMID- 17519453
TI  - Getting involved in professional policy development.

PMID- 17519454
TI  - Eradicating analgesic use of meperidine in a hospital.

PMID- 17519455
TI  - Managing wholesaler agreements in the fee-for-service era.

PMID- 17519457
TI  - Treatment of cholestatic pruritus in children.
AB  - PURPOSE: The treatment of cholestatic pruritus in children is reviewed. SUMMARY:
      Cholestasis is characterized by an accumulation of substances that are normally
      secreted in the bile. Pruritus is a well-known feature of chronic cholestasis in
      both adults and children and has been reported as the most incapacitating symptom
      in children with chronic liver disease. Traditional agents, such as
      antihistamines, are typically ineffective as monotherapy in controlling
      cholestatic pruritus. As a result, clinicians have looked to other agents, such
      as rifampin, phenobarbital, ursodiol, opioid antagonists, and bile-binding
      resins, for attaining better control of pruritic symptoms. Each agent
      demonstrates different levels of efficacy in pediatric and adult literature.
      There are no guidelines or algorithms to guide therapy with these agents for
      children. As a result, an agent should be selected based on the patient's
      concurrent diseases and current medication regimen. Cholestyramine and ursodiol
      are both safe and inexpensive, with documented efficacy for cholestatic pruritus
      in children. Because cholestatic pruritus is likely a result of multiple
      mechanisms, combination therapy with agents that have differing mechanisms of
      action might be beneficial and could capitalize on potential synergy between the
      agents used. Future therapy for cholestatic pruritus may include serotonin
      antagonists, selective serotonin-reuptake inhibitors, and leukotriene
      antagonists. CONCLUSION: Depending on the underlying disease state resulting in
      cholestasis, phenobarbital, ursodiol, bile sequestering agents, and opioid
      antagonists appear to be most effective for treating pruritus related to
      intrahepatic cholestasis. Alternatively, rifampin appears to be the only agent
      with reported treatment efficacy for pruritus related to extrahepatic
      cholestasis.

PMID- 17519458
TI  - Resumption of high-dose methotrexate after methotrexate-induced nephrotoxicity
      and carboxypeptidase G2 use.
AB  - PURPOSE: The successful resumption of high-dose methotrexate in a 13-year-old boy
      with recurrent anaplastic large-cell lymphoma (ALCL) who suffered renal
      dysfunction after a 24-hour infusion of high-dose methotrexate and required
      treatment with carboxypeptidase G(2) (CPDG(2) ) is described. SUMMARY: A 13-year
      old boy who had been diagnosed in 2001 with stage I ALCL was admitted to the
      hospital in February 2005 after he developed a smaller left axillary mass in the
      area of his original mass. Recurrent ALCL was diagnosed, and treatments were
      initiated based on branch K3 of the protocol published in the non-Hodgkin's
      lymphoma-Berlin-Frankfurt-Munster (NHL-BFM) trial 90. In the NHL-BFM 90 protocol,
      all AA and BB courses include high-dose methotrexate therapy, which consists of
      aggressive alkalinized hydration, methotrexate 5 g/m(2) given as an i.v. infusion
      over 24 hours, and leucovorin rescue. During course BB2, the boy's serum
      methotrexate values exceeded NHL-BFM goals at 36, 42, and 48 hours. Because the
      patient's elimination of methotrexate remained slow and his serum creatinine
      level remained above normal limits, CPDG(2) was obtained for the treatment of
      methotrexate toxicity. The patient tolerated the CPDG(2) without adverse effects,
      and the patient's serum methotrexate concentration decreased from 14.47 to 0.66
      microM. The patient went on to complete six courses based on the protocol. High
      dose methotrexate was resumed at 50% then 100% of the original dose. He is
      currently in remission on maintenance therapy. CONCLUSION: A 13-year-old boy with
      recurrent ALCL had methotrexate-induced nephrotoxicity following high-dose
      methotrexate. The resultant delayed methotrexate clearance required the standard
      therapies as well as use of investigational CPDG(2). High-dose methotrexate was
      successfully resumed.

PMID- 17519459
TI  - Educational interventions to reduce use of unsafe abbreviations.
AB  - PURPOSE: Educational interventions to reduce the use of abbreviations and dosage
      designations that were deemed unsafe at a level 1 trauma center are described.
      SUMMARY: Strategies to reduce the use of unsafe abbreviations at Detroit
      Receiving Hospital were studied. Six abbreviations and dosage designations were
      deemed as unsafe by the site's medication-use and patient medical safety
      committees: (1) U for units, (2) microg for microgram, (3) TIW for three times a
      week, (4) the degree symbol for hour, (5) trailing zeros after a decimal point,
      and (6) the lack of leading zeros before a decimal point. Data on abbreviation
      use was collected starting in September 2003 by examining copies of patients'
      order sheets, which are sent from nursing units to the pharmacy for processing.
      Data were collected during three 24-hour periods each month, with 7-10 days
      between each period. A data collection sheet was developed to assist in
      documenting the number of opportunities for each unsafe abbreviation and the
      actual incidence of each. Educational strategies were developed and implemented
      starting in October 2003 to decrease the use of the unsafe abbreviations. These
      strategies included inservice education programs for the medical, pharmacy, and
      nursing staffs; laminated pocket cards; patient chart dividers; stickers; and
      interventions by pharmacists and nurses during medication prescribing. During the
      eight-month evaluation period, 20,160 orders were reviewed, representing 27,663
      opportunities to use a designated unsafe abbreviation. Educational interventions
      successfully reduced the overall incidence of unsafe abbreviations from 19.69% to
      3.31%. CONCLUSION: Educational interventions markedly reduced the use of unsafe
      abbreviations in medication orders over an eight-month evaluation period.

PMID- 17519460
TI  - Evidence-based review of the black-box warning for droperidol.
AB  - PURPOSE: Data collected from the Food and Drug Administration (FDA) under the
      Freedom of Information Act are presented to help clinicians understand the data
      prompting the black-box warning for droperidol and to make educated decisions
      regarding the use of droperidol and alternative agents. SUMMARY: A written
      request was submitted to FDA to provide a report of any and all reports of
      cardiovascular adverse events related to droperidol that were part of the
      decision to add a black-box warning to the label of droperidol. The report listed
      277 cases of adverse effects associated with droperidol since its introduction to
      the market in 1970. Many of the reports were duplicates, leaving a total of 65
      individual cases. Of these cases, only 2 described adverse effects possibly
      caused by droperidol in dosages commonly used in the United States. In addition
      to these reports, the results of two European studies prompted FDA to make the
      decision for the black-box warning. Both studies used droperidol doses 50-100
      times higher than those used in the United States. CONCLUSION: Studies show that
      there is a dose-dependent increase in the rate of adverse cardiovascular events
      when droperidol is used either alone or in combination with other medications
      that cause Q-T interval prolongation. At this time, there does not appear to be
      significant evidence to suggest that serotonin type 3-receptor (5-HT(3))
      antagonists are safer than droperidol with regard to Q-T interval prolongation.
      More studies are needed to determine the safety and efficacy of droperidol when
      used in doses of 0.625-1.25 mg compared with the 5-HT(3) antagonists.

PMID- 17519461
TI  - Valsartan versus lisinopril or extended-release metoprolol in preventing
      cardiovascular and renal events in patients with hypertension.
AB  - PURPOSE: The objective of this study was to compare cardiovascular and renal
      events in patients with hypertension receiving the angiotensin II-receptor
      blocker valsartan versus those receiving the angiotensin-converting-enzyme
      lisinopril or the beta-blocker metoprolol succinate in an extended-release
      formulation. METHODS: A retrospective study was conducted using a health
      insurance claims database spanning the period from January 1997 through December
      2003 and representing approximately 40 million members enrolled in over 70 health
      plans across the United States. Study subjects included all persons in the
      database with two or more outpatient prescriptions for valsartan, lisinopril, or
      extended-release metoprolol and two or more prior claims with a diagnosis of
      hypertension. Those with a history of major cardiovascular or renal events
      (diagnosis of myocardial infarction, stroke, heart failure, ventricular
      arrhythmias, or cardiac arrest; coronary revascularization procedure; diagnosis
      of renal failure; or dialysis or kidney transplantation) or using other
      antihypertensive medications except diuretics during the 12 months before
      treatment with valsartan, lisinopril, or extended-release metoprolol were
      excluded. Risks of major cardiovascular or renal event during follow-up were
      analyzed using Cox proportional hazards regression. RESULTS: A total of 29,357
      antihypertensive patients were identified who initiated therapy with valsartan (n
      = 6,645), lisinopril (n = 17,320), or extended-release metoprolol (n = 5,392). In
      multivariate analyses, therapy with valsartan was associated with a significantly
      lower risk of a major cardiovascular or renal event versus extended-release
      metoprolol (heart rate [HR], 0.70; 95% confidence interval [CI], 0.56-0.87; p =
      0.0015). Patients receiving valsartan had a nominally lower risk of a major
      cardiovascular or renal event than those receiving lisinopril, although this
      difference was not statistically significant (HR, 0.89; 95% CI, 0.74-1.07; p =
      0.1987). CONCLUSION: Results of this observational study suggest that the use of
      valsartan may reduce the risk of major cardiovascular and renal events compared
      with extended-release metoprolol.

PMID- 17519462
TI  - Internal reporting system to improve a pharmacy's medication distribution
      process.
AB  - PURPOSE: The current pharmacy occurrence-reporting system in an institution was
      reviewed, and an internal procedure that would provide data to improve the
      medication-use process was developed. SUMMARY: In a rural, 353-bed, tertiary care
      academic center, the effectiveness of a departmental occurrence-reporting system
      was determined over a nine-month period to increase occurrence reporting within
      the pharmacy and allow administrators to identify specific areas for improvement
      within the medication distribution process. These events were identified
      according to the number and type of near misses documented by pharmacy staff. The
      pharmacy staff was asked to complete a survey about the department's current
      reporting process and what the staff desired in a new occurrence-reporting
      system. The staff was also surveyed on which steps of the pharmacy's medication
      distribution process could contribute to the most errors. Initially, a paper
      based error-reporting form was developed for all steps of the pharmacy
      distribution process except pharmacist order entry. Once the paper-based error
      reporting form was introduced, the pharmacist order-entry phase of the project
      was begun. During the evaluation period, 203 pharmacy-dispensing errors were
      reported to the hospital's error-reporting system. In contrast, 1385 total
      pharmacy events were documented using the pharmacy's internal occurrence
      reporting system. At least 204 of those reported events involved high-alert
      medications according to the institution's high-alert medications policy.
      CONCLUSION: A pharmacy internal occurrence-reporting system increased staff
      reporting and identified areas for improvement within the medication distribution
      process that may not have been recorded by a hospital-based reporting system.

PMID- 17519463
TI  - Survey of hospitals for guidelines, policies, and protocols for anticoagulants.
AB  - PURPOSE: A survey of community hospitals that are part of a national group
      purchasing organization (GPO) was conducted to assess the formulary status of
      currently available anticoagulants, assess the current status of anticoagulant
      prescribing guidelines and the existing scope of such guidelines, and identify
      perceptions about the appropriateness of the use of anticoagulants in community
      hospitals in the United States. METHODS: A Web-based survey of acute care
      hospitals that were members of a leading health care resource management and GPO
      was conducted. The survey was sent to 224 hospitals. RESULTS: Of 224 hospitals,
      127 participated in the survey, a response rate of 59.6%. Warfarin,
      unfractionated heparin (UFH), and enoxaparin were the anticoagulants most
      commonly included (>80%) on the hospitals' drug formularies. Guidelines relating
      to the use of UFH and low-molecular-weight heparins (LMWHs) existed in
      approximately 87.4% and 55.1% of responding hospitals, respectively, followed by
      warfarin and direct thrombin inhibitors (DTIs) (approximately 44.1% and 30.7%,
      respectively). Among hospitals without guidelines, 78.2%, 72.1%, 65.4%, 50.0%,
      and 41.4% reported that such guidelines would be useful if they included LMWHs,
      warfarin, DTIs, UFH, and fondaparinux, respectively. Guidelines for prophylaxis
      of venous thromboembolism (VTE), appropriate drug selection, and dosing for VTE
      prophylaxis and treatment existed in 59.8%, 53.5%, and 43.3% of the hospitals,
      respectively. CONCLUSION: The study found that a sizable percentage of the
      responding community hospitals did not have guidelines, protocols, or policies
      related to the use of anticoagulants. Further, those hospitals without such
      guidelines commonly reported a need for clinical practice guidelines.

PMID- 17519464
TI  - Physical and chemical stability of palonosetron hydrochloride with five opiate
      agonists during simulated Y-site administration.
AB  - PURPOSE: The physical and chemical compatibility of palonosetron hydrochloride
      with fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride,
      morphine sulfate, and sufentanil citrate during simulated Y-site administration
      was studied. METHODS: Test samples were prepared in triplicate by mixing 7.5-mL
      samples of undiluted palonosetron 50 microg/mL (of palonosetron) with 7.5-mL
      samples of fentanyl citrate 50 microg/mL, morphine sulfate 15 mg/mL,
      hydromorphone hydrochloride 0.5 mg/mL, meperidine hydrochloride 10 mg/mL, and
      sufentanil citrate 12.5 microg/mL (of sufentanil) per milliliter individually in
      colorless 15-mL borosilicate glass screw-cap culture tubes with polypropylene
      caps. Physical stability of the admixtures was assessed by visual examination and
      by measuring turbidity and particle size and content. Chemical stability was
      assessed by stability-indicating high-performance liquid chromatography.
      Evaluations were performed immediately and one and four hours after mixing.
      RESULTS: All of the admixtures were initially clear and colorless in normal
      fluorescent room light and when viewed with a high-intensity monodirectional
      light (Tyndall beam) and were essentially without haze. Changes in turbidity were
      minor throughout the study. Particulates measuring 10 microm or larger were few
      in all samples throughout the observation period. The admixtures remained
      colorless throughout the study. No loss of palonosetron hydrochloride occurred
      with any of the opiate agonists tested over the four-hour period. Similarly,
      little or no loss of the opiate agonists occurred over the four-hour period.
      CONCLUSION: Palonosetron hydrochloride was physically and chemically stable with
      fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride, morphine
      sulfate, and sufentanil citrate during simulated Y-site administration.

PMID- 17519472
TI  - Medicaid agencies as managed care organizations: an "actuarially sound" solution?

PMID- 17519473
TI  - Distributing State Children's Health Insurance Program funds: a critical review
      of the design and implementation of the funding formula.
AB  - The development of formulas to distribute federal funds to states based on
      demographic data continues to challenge data and policy analysts. Analysts must
      forward the best objective statistical analysis and data inputs to formula
      specifications while acknowledging the politics of the legislative process that
      authorizes federal funding formulas. This article evaluates the federal funding
      formula for the State Children's Health Insurance Program (SCHIP) using key
      formula components of need, effort, capacity, and performance. We also examine
      the operationalization and measure of the target population in the SCHIP funding
      formula. Legislative decisions on formulas are, by nature, based on compromises
      that balance competing policy objectives. The analyst's role is to continually
      review current research standards, data quality, and relevant formula inputs and
      make recommendations to refine federal funding formulas to better target
      resources to their intended populations.

PMID- 17519474
TI  - The political management of managed care: explaining variations in state health
      maintenance organization regulations.
AB  - In the 1990s, strong incentives for managed care organizations to control costs,
      once regarded as a fortuitous confluence of interests, came to be seen as
      antithetical to consumers' interests in quality of care. In response to this
      change in political climate, many states have greatly increased their regulatory
      control of managed care organizations since the mid-1990s. This activity is
      surprising in an era when public policy on health care issues is usually
      described as frozen, gridlocked, and/or stalemated as a result of intense
      activity on the part of organized interests. We take advantage of the variation
      in state regulations of health maintenance organizations (HMOs) to discover why
      some governments are able to address policy problems that are often perceived as
      intractable in a political if not in a true policy sense. From the history of
      HMOs, the backlash against managed care, and state responses to that backlash, we
      first extract a number of hypotheses about state regulatory activity. We then
      test these hypotheses with data on regulatory adoptions by states during the late
      1990s and the early 2000s. Last, we discuss the findings with special attention
      to the role of politics in health care.

PMID- 17519475
TI  - Different countries, different needs: the role of private health insurance in
      developing countries.
AB  - This article discusses the role of private health insurance (PHI) in developing
      countries. Three broad regional clusters are identified that share similar
      characteristics and policy challenges for the effective integration of private
      insurance into national health care systems: (1) Latin America and Eastern
      Europe, where there are already developed insurance industries facing important
      market and policy failures; (2) the Middle East/North Africa region and East
      Asia, where there is a projected strong growth of PHI that needs to be
      accompanied by efficient regulation; and finally, (3) South Asia and Sub-Saharan
      Africa, where PHI will only play a marginal role in the foreseeable future while
      the scaling up of small-scale, nonprofit insurance schemes appears to be of
      critical importance. Overall, this survey shows that the role of private
      insurance varies depending on the economic, social, and institutional settings in
      a country or region. Private health insurance schemes can be valuable tools to
      complement existing health-financing options only if they are carefully managed
      and adapted to local needs and preferences.

PMID- 17519476
TI  - Body measures in relation to gastro-oesophageal reflux.

PMID- 17519477
TI  - Prospective comparison of secretin-stimulated MRCP with manometry in the
      diagnosis of sphincter of Oddi dysfunction types II and III.

PMID- 17519478
TI  - Are we meeting the standards set for ERCP?

PMID- 17519480
TI  - Abdominal pain following cardiac transplantation.

PMID- 17519479
TI  - Cardiovascular determinants of survival in cirrhosis.

PMID- 17519481
TI  - Extremely rare anal nodules in a rare disease.

PMID- 17519484
TI  - Dysphagia following fish bone ingestion.

PMID- 17519485
TI  - Bad breath and weight loss.

PMID- 17519488
TI  - Complication of therapeutic endoscopic retrograde cholangiopancreatography.

PMID- 17519490
TI  - Treatment options for patients with severe gastroparesis.

PMID- 17519491
TI  - Inadequate statistical power in Barrett's oesophagus ablation study.

PMID- 17519492
TI  - Hepatitis C virus clearance and gender.

PMID- 17519493
TI  - Development of a bioartificial new intestinal segment using an acellular matrix
      scaffold.

PMID- 17519494
TI  - No evidence of persisting measles virus in the intestinal tissues of patients
      with inflammatory bowel disease.

PMID- 17519495
TI  - Clostridium difficile-associated diarrhoea: bovine anti-Clostridium difficile
      whey protein to help aid the prevention of relapses.

PMID- 17519496
TI  - Is gliadin really safe for non-coeliac individuals? Production of interleukin 15
      in biopsy culture from non-coeliac individuals challenged with gliadin peptides.

PMID- 17519497
TI  - The value of endothelin 1 in the early diagnosis of severe intestinal
      strangulation.

PMID- 17519498
TI  - The RANTES -28 g polymorphism is associated with primary sclerosing cholangitis.

PMID- 17519499
TI  - Increased risk of colorectal neoplasia in asymptomatic liver-transplant
      recipients.

PMID- 17519500
TI  - Visceral leishmaniasis causes fever and decompensation in patients with
      cirrhosis.

PMID- 17519501
TI  - Magnifying videoendoscopic findings of Peyer's patches in the terminal ileum of
      Crohn's disease.

PMID- 17519502
TI  - Internationalisation of high-impact gastroenterology journals, 1970-2005.

PMID- 17519503
TI  - Molecular signaling involved in regulating feeding and other motivated behaviors.
AB  - The metabolic and nutritional status of an organism influences multiple behaviors
      in addition to food intake. When an organism is hungry, it employs behaviors that
      help it locate and ingest food while suppressing behaviors that are not
      associated with this goal. Alternatively, when an organism is satiated, food
      seeking behaviors are repressed so that the animal can direct itself to other
      goal-oriented tasks such as reproductive behaviors. Studies in both vertebrate
      and invertebrate model systems have revealed that food-deprived and -satiated
      behaviors are differentially executed and integrated via common molecular
      signaling mechanisms. This article discusses cellular and molecular mechanisms
      for how insulin, neuropeptide Y (NPY), and serotonin utilize common signaling
      pathways to integrate feeding and metabolic state with other motivated behaviors.
      Insulin, NPY, and serotonin are three of the most well-studied molecules
      implicated in regulating such behaviors. Overall, insulin signaling allows an
      organism to coordinate proper behavioral output with changes in metabolism, NPY
      activates behaviors required for locating and ingesting food, and serotonin
      modulates behaviors performed when an organism is satiated. These three molecules
      work to ensure that the proper behaviors are executed in response to the feeding
      state of an organism.

PMID- 17519504
TI  - Cofilin-mediated neurodegeneration in Alzheimer's disease and other
      amyloidopathies.
AB  - Transport defects may arise in various neurodegenerative diseases from failures
      in molecular motors, microtubule abnormalities, and the chaperone/proteasomal
      degradation pathway leading to aggresomal-lysosomal accumulations. These defects
      represent important steps in the neurodegenerative cascade, although in many
      cases, a clear consensus has yet to be reached regarding their causal
      relationship to the disease. A growing body of evidence lends support to a link
      between neurite transport defects in the very early stages of many
      neurodegenerative diseases and alterations in the organization and dynamics of
      the actin cytoskeleton initiated by filament dynamizing proteins in the
      ADF/cofilin family. This article focuses on cofilin, which in neurons under
      stress, including stress induced by the amyloid-beta (Abeta) 1-42 peptide,
      undergoes dephosphorylation (activation) and forms rod-shaped actin bundles
      (rods). Rods inhibit transport, are sites of amyloid precursor protein
      accumulation, and contribute to the pathology of Alzheimer's disease. Because
      rods form rapidly in response to anoxia, they could also contribute to synaptic
      deficits associated with ischemic brain injury (e.g., stroke). Surprisingly,
      cofilin undergoes phosphorylation (inactivation) in hippocampal neurons treated
      with Abeta1-40 at high concentrations, and these neurons undergo dystrophic
      morphological changes, including accumulation of pretangle phosphorylated-tau.
      Therefore, extremes in phosphoregulation of cofilin by different forms of Abeta
      may explain much of the Alzheimer's disease pathology and provide mechanisms for
      synaptic loss and plaque expansion.

PMID- 17519505
TI  - Developmental role of tryptophan hydroxylase in the nervous system.
AB  - The serotonin 5-hydroxytryptamine (5-HT) neurotransmitter system contributes to
      various physiological and pathological conditions. 5-HT is the first
      neurotransmitter for which a developmental role was suspected. Tryptophan
      hydroxylase (TPH) catalyzes the rate-limiting reaction in the biosynthesis of 5
      HT. Both TPH1 and TPH2 have tryptophan hydroxylating activity. TPH2 is abundant
      in the brain, whereas TPH1 is mainly expressed in the pineal gland and the
      periphery. However, TPH1 was found to be expressed predominantly during the late
      developmental stage in the brain. Recent advances have shed light on the kinetic
      properties of each TPH isoform. TPH1 showed greater affinity for tryptophan and
      stronger enzymic activity than TPH2 under conditions reflecting those in the
      developing brain stem. Transient alterations in 5-HT homeostasis during
      development modify the fine wiring of brain connections and cause permanent
      changes to adult behavior. An increasing body of evidence suggests the
      involvement of developmental brain disturbances in psychiatric disorders. These
      findings have revived a long-standing interest in the developmental role of 5-HT
      related molecules. This article summarizes our understanding of the kinetics and
      possible neuronal functions of each TPH during development and in the adult.

PMID- 17519507
TI  - Caenorhabditis elegans as a model system to study aging of learning and memory.
AB  - The nematode Caenorhabditis elegans is an excellent model organism to study
      biological processes relevant to a wide variety of human and rodent disease
      systems. Previous studies have suggested that mutants of the insulin/insulin-like
      growth factor-1 pathway show life extension and increased stress resistance in
      various species, including C. elegans, the fruit fly, and the mouse. It has
      recently been shown that the life-extending mutants, including the age-1
      phosphatidylinositol- 3 OH kinase mutants and the daf-2 insulin-like receptor
      mutants, display improvement in a type of associative learning behavior called
      thermotaxis learning behavior. The age-1 mutant shows a dramatic threefold
      extension of the health-span that ensures thermotaxis learning behavior,
      suggesting strong neuroprotective actions during aging. The age-1 and daf-2
      mutants show resistance to multiple forms of stress and upregulates the genes
      involved in reactive oxygen species scavenging, heat shock, and P450 drug
      detoxification. The life-extending mutants may confer resistance to various
      stress and diseases in neurons. Therefore, C. elegans provides an emerging system
      for the prevention of age-related deficits in the nervous system and in learning
      behaviors. This article discusses the aging of learning and memory and the
      neuroprotection effects of life-extending mutants on learning behaviors.

PMID- 17519506
TI  - Neuroprotection against neurodegenerative diseases: development of a novel hybrid
      neuroprotective peptide Colivelin.
AB  - Neuronal death is directly implicated in the pathogenesis of neurodegenerative
      diseases (NDDs). NDDs cannot be cured because the mechanisms underlying neuronal
      death are too complicated to be therapeutically suppressed. Neuroprotective
      factors, such as neurotrophins, certain growth factors, neurotrophic cytokines,
      and short neuroprotective peptides, support neuronal survival in both
      physiological and pathological conditions, suggesting that these factors may be
      good drug candidates for NDDs. We recently generated a novel neuroprotective
      peptide named Colivelin by attaching activity-dependent neurotrophic factor
      (ADNF) to the N-terminus of a potent Humanin derivative, AGA-(C8R)HNG17. HN was
      originally identified from an Alzheimer's disease (AD) brain as an endogenous
      neuroprotective peptide that suppresses ADrelevant toxicity. Colivelin protects
      neurons from death relevant to NDDs by activating two independent prosurvival
      signals: an ADNF-mediated Ca2+/calmodulin-dependent protein kinase IV pathway and
      an HN-mediated STAT3 pathway. The neuroprotective effect of Colivelin provides
      novel insights into therapy for NDDs.

PMID- 17519509
TI  - Tandem couture: Cys-loop receptor concatamer insights and caveats.
AB  - Receptor subunits in the Cys-loop superfamily assemble to form channels as
      homopentamers or heteropentamers, expanding functional diversity through
      modularity. Expression of two or more compatible subunit types can lead to
      various receptor assemblies or subtypes. However, what may be good for diversity
      in vivo may be undesirable for the bench scientist, because we often wish to
      reduce our analyses to a single receptor subtype. By linking two or more
      subunits, creating tandems or concatamers, we can control stoichiometry and limit
      expression to exactly one receptor subtype. In this fashion, receptors with mixed
      subunit subtypes and heterozygous mutations can be separated from a mixture and
      can be described in detail. However, several recent studies have shown that this
      may be more easily conceived than accomplished, because several unforeseen
      problems have arisen. Concatamers can degrade, linkers can sometimes be clipped
      after or during translation, and one subunit may "loop out" or even become part
      of a second (now linked) pentamer with different characteristics. Some strategies
      have been developed to overcome these drawbacks, and the resultant new
      information that has begun to emerge has revitalized the study of these receptors
      in heterologous expression systems.

PMID- 17519508
TI  - Cocaine withdrawal and neuro-adaptations in ion channel function.
AB  - Chronic exposure to psychostimulants induces neuro-adaptations in ion channel
      function of dopamine (DA)-innervated cells localized within the medial prefrontal
      cortex (mPFC) and nucleus accumbens (NAc). Although neuroplasticity in ion
      channel function is initially found in drug-sensitized animals, it has recently
      been believed to underlie the withdrawal effects of cocaine, including craving
      that leads to relapse in human addicts. Recent studies have also revealed
      remarkable differences in altered ion channel activities between mPFC pyramidal
      neurons and medium spiny NAc neurons in cocaine-withdrawn animals. In response to
      psychostimulant or certain "excitatory" stimuli, increased intrinsic excitability
      is found in mPFC pyramidal neurons, whereas decreased excitability is observed in
      medium spiny NAc cells in drug-withdrawn animals compared to drug-free control
      animals. These changes in ion channel function are modulated by interrupted
      DA/Ca2+ signaling with decreased DA D2 receptor function but increased D1
      receptor signaling. More importantly, they are correlated to behavioral changes
      in cocaine-withdrawn human addicts and sensitized animals. Based on growing
      evidence, researchers have proposed that cocaine-induced neuro-adaptations in ion
      channel activity and DA/Ca2+ signaling in mPFC pyramidal neurons and medium spiny
      NAc cells may be the fundamental cellular mechanism underlying the cocaine
      withdrawal effects observed in human addicts.

PMID- 17519510
TI  - Do we need new drugs for the treatment of type 2 diabetes mellitus?

PMID- 17519511
TI  - Heterozygous alpha-I antitrypsin deficiency as a co-factor in the development of
      chronic liver disease: a review.
AB  - Alpha-I antitrypsin (AIAT) is an acute-phase protein that is produced in liver
      cells. AIAT deficiency is a hereditary disease which is defined by the hepatic
      production of an abnormal protein that can not be released into the plasma. This
      leads to deficiency of plasma AIAT and subsequently to an impaired protection
      against proteases, resulting in pulmonary disease. Accumulation of the abnormal
      protein in hepatocytes can lead to liver damage. Serum level measurement,
      phenotyping and liver biopsy can be used for establishing the diagnosis.
      Homozygous AIAT deficiency can cause neonatal hepatitis; in adults end-stage
      liver disease, cirrhosis and hepatocellular carcinoma can develop. There are
      strong arguments to consider heterozygous AIAT deficiency as an important co
      factor in the aetiology of chronic liver disease. Studies have shown that AIAT
      heterozygosity can be considered a modifier for hepatitis C virus, end-stage
      liver disease, cirrhosis and hepatocellular carcinoma. The accumulation of AIAT
      in the hepatocytes occurs more profoundly in a diseased liver, and as a
      consequence it affects the natural course of the liver disease. Therapeutic
      options include augmentation therapy (infusion of purified human plasma AIAT) in
      pulmonary disease; in end-stage liver disease liver transplantation is an option.
      For the future, other interventions such as gene therapy or strategies to inhibit
      polymerisation are promising.

PMID- 17519512
TI  - Non-evidence-based variables affecting physicians' test-ordering tendencies: a
      systematic review.
AB  - BACKGROUND: The concept of evidence-based medicine (EBM) was introduced in 1992.
      Incorporation of EBM into physicians' practices, however, has been slow.
      Testordering tendencies are still based on variables that are not necessarily
      evidence-based. METHODS: The literature was reviewed to identify the non-EBM
      variables that affect physicians' practices of test ordering. Studies of interest
      were limited to original research on the determinants of physicians' test
      ordering tendencies. The search strategy included queries in MEDLINE (1992-2006),
      Web of Science (1993-2006), EMBASE (1992-2006), and PsycINFO (1992-2006);
      checking of reference lists; hand searching relevant journals; and personal
      communication with experts. Two independent reviewers abstracted information on
      the design, quality, and limitations of the study. Review articles, letters, and
      editorials were excluded from analysis. RESULTS: 104 original studies reporting
      on the variables affecting test ordering were identified. Of these, 53 studies
      assessing physician variables affecting test ordering were identified. Some of
      the recognisable physician factors included age, sex, degree of specialisation,
      geographic location and practice setting, individual belief systems, experience,
      knowledge, fear of malpractice litigation, physician regret, financial
      incentives, awareness of costs of tests ordered, and provision of written
      feedback by peers or employers. CONCLUSION: Despite considerable advances in our
      understanding of EBM and its application to patient care, several non-EBM
      physician variables influence physicians' test-ordering characteristics. Ongoing
      effort is needed to identify the modifiable non-EBM determinants of physicians'
      test ordering and to use appropriate tools and techniques to encourage evidence
      based behaviours for test ordering.

PMID- 17519513
TI  - Single-centre experience with nonmyeloablative allogeneic stem cell
      transplantation in patients with multiple myeloma: prolonged remissions induced.
AB  - BACKGROUND: The role of allogeneic stem cell transplantation in multiple myeloma
      is not yet established. METHODS: We retrospectively evaluated the outcome of
      nonmyeloablative allogeneic stem cell transplantation (NMA) in patients with
      multiple myeloma treated at the Department of Haematology of the University
      Medical Centre Utrecht. Thirty-six patients received NMA as part of the first
      line treatment; 23 patients as part of salvage therapy. Conditioning regimen was
      low-dose total body irradiation (TBI, 2 Grays) only; fludarabine was added in
      patients without previous autologous stem cell transplantation and patients with
      matched unrelated donors received antithymocyte globulin in addition to
      fludarabine and TBI. RESULTS: Following NMA overall response increased from 84 to
      90%, complete remission rate from 15 to 32%. As part of first-line treatment NMA
      induced complete remission in 50% of patients vs one patient (4%) treated for
      relapsed multiple myeloma. Median progression-free survival was 26 months (13
      months for the salvage group, 38 months for the 'upfront' patients). Median
      overall survival has not been reached yet. The achievement of complete remission
      following NMA as part of first-line treatment was associated with prolonged
      progression-free and overall survival. Major toxicities were acute and chronic
      graft-vs-host disease occurring in 64% (23% grade 3-4) and in 54% (49% extensive)
      patients, respectively. Seven patients (12%) died from nonrelapse mortality, five
      patients (9%) directly related to toxicity of NMA. CONCLUSION: NMA in multiple
      myeloma is feasible, is associated with acceptable nonrelapse mortality and may
      induce prolonged complete remission. In pretreated patients the result of NMA is
      disappointing which urges new strategies.

PMID- 17519514
TI  - Papillary thyroid carcinoma in a patient with sarcoidosis treated with
      minocycline.
AB  - Long-term treatment with minocycline is occasionally associated with the
      development of black thyroid syndrome in which thyroid cancer is frequently
      found. Here, we report a patient with cutaneous, pulmonary and thyroid
      sarcoidosis who developed papillary thyroid carcinoma in the presence of a black
      thyroid syndrome after being treated with minocycline for 2.5 years.

PMID- 17519515
TI  - An itchy holiday.
AB  - A 33-year-old Dutch woman developed itchy skin lesions during a beach holiday in
      Thailand. She was treated for various diagnoses, without success. Finally she was
      successfully treated for a clinically suspected hookwormrelated folliculitis. A
      brief overview of hookworm-related folliculitis is given.

PMID- 17519516
TI  - Rare localisation of air.

PMID- 17519517
TI  - Recurrent pericardial effusion with a common clinical disorder.
AB  - We present a case of recurrent pericardial effusion in a patient with Down's
      syndrome in whom the underlying cause was not considered because of unfamiliarity
      with the care of people with Down's syndrome. The diagnosis hypothyroidism only
      became apparent by means of a routine panel of biochemical tests.

PMID- 17519519
TI  - H1foo is indispensable for meiotic maturation of the mouse oocyte.
AB  - Oocyte-specific linker histone H1foo is localized in the oocyte nucleus, either
      diffusely or bound to chromatin, during the processes of meiotic maturation and
      fertilization. This expression pattern suggests that H1foo plays a key role in
      the control of gene expression and chromatin modification during oogenesis and
      early embryogenesis. To reveal the function of H1foo, we microinjected antisense
      morpholino oligonucleotides (MO) against H1foo into mouse germinal-vesicle stage
      oocytes. The rate of in vitro maturation of the antisense MO group was
      significantly lower than that of the control group. Eggs that failed to extrude a
      first polar body following injection of antisense MO arrested at metaphase I.
      Additionally, co-injection of in vitro synthesized H1foo mRNA along with
      antisense MO successfully rescued expression of H1foo and improved the in vitro
      maturation rate. There was no difference in the rate of parthenogenesis between
      the antisense MO and control groups. These results indicate that H1foo is
      essential for maturation of germinal vesicle-stage oocytes.

PMID- 17519520
TI  - Seasonal changes in semen characteristics, composition of seminal plasma and
      frequency of acrosome reaction induced by calcium and calcium ionophore A23187 in
      Large White boars.
AB  - This study attempted to explain the mechanisms regulating boar fertility by
      examining seasonal changes in semen characteristics, the composition of seminal
      plasma and responsiveness of sperm acrosomes to Ca(2+) and the Ca(2+) ionophore
      A23187 (Ca(2+)/A23187). Sperm-rich and sperm-poor fractions were separately
      collected from 3 mature fertile Large White boars once a month over a one-year
      period. During the period of study, ambient temperature and relative humidity
      were recorded for within the stall in which the boars were kept and the semen
      characteristics, composition of the seminal plasma of sperm-rich fractions, and
      occurrence of the acrosome reaction in response to Ca(2+) (3 mM)/A23187 (0.3
      microM) were examined. The highest mean maximum and minimum ambient temperatures
      were recorded in August-September, whereas the lowest mean maximum and minimum
      ambient temperatures were recorded in December and January, respectively. There
      was a moderate peak in relative humidity from July to October. The lowest
      percentages of motile spermatozoa and of spermatozoa with intact acrosomes and
      highest percentage of spermatozoa with abnormal morphology and strongest
      agglutination were seen in August-September. The total protein and albumin
      concentrations were lowest in August-September. Testosterone levels increased
      gradually as day length decreased after the summer solstice (June) and peaked in
      October-November. The percentage of acrosome reactions in response to
      Ca(2+)/A23187 was highest with the quickest response in August-September, as
      shown by the shortest time required for 50% of relative acrosome reactions. The
      farrowing rates were lowest in these same 2 months. These results suggest that
      seasonal infertility in Large White boars may be due, at least in part, to a
      combination of low motility, abnormal morphology including acrosomal abnormality,
      and early occurrence of the acrosome reaction in response to stimulus, possibly
      resulting from a decrease in acrosomal stabilizing proteins in the seminal plasma
      during summer. These changes may be modulated by heat/humidity stress and/or
      photoperiod-regulated testosterone.

PMID- 17519521
TI  - A simple method for selection of cumulus-oocyte complexes from bovine ovaries by
      sedimentation with percoll.
AB  - Selection of bovine cumulus-oocyte complexes (COCs) for in vitro embryo
      production (IVP) is generally based on the morphological characteristics of the
      cumulus cells surrounding the oocytes and the ooplasm under microscopic
      observation. The purpose of this study was to examine a simple method for
      selection of COCs by sedimentation with Percoll solutions. COCs were aspirated
      from ovaries derived from a local slaughterhouse, and the COCs were classified by
      the morphology of their cumulus cell layers, as follows: Class A, compact and
      thick; Class B, compact but thin; Class C, partially denuded and thin; and Class
      D, denuded. Percoll solutions were prepared by diluting Percoll to 7.5, 10, 12.5,
      15, 17.5, 20, 22.5, 25, 27.5 and 30% solutions, respectively. COCs were placed on
      the surface of the Percoll solution for 3 min, and the precipitated COCs were
      transferred to stepwise high density solution. The percentage of Percoll solution
      just before buoyancy was considered to the specific sedimentary value of the COC
      and oocyte. The mean sedimentary value of Class A COCs was higher than those of
      the other classes (P<0.01). The mean sedimentary values of denuded oocytes from
      Classes A and B were higher than those from Classes C and D (P<0.01). Our results
      show that sedimentation of COCs and denuded oocytes was generally related to the
      morphological quality of the COCs, although the sedimentary values ranged widely
      for one class of COCs and oocytes. The Percoll method can be used for simple
      selection of COCs.

PMID- 17519522
TI  - Direct effects of prolactin on adrenal steroid release in male Hatano high
      avoidance (HAA) rats may be mediated through Janus kinase 2 (Jak2) activity.
AB  - Prolactin (PRL) has been proposed to directly stimulate corticosterone release.
      However, the role of PRL on adrenocortical function in male HAA rats has not been
      fully clarified. The aim of this study was to investigate the effect of PRL on
      the secretion of corticosterone and progesterone using an in vitro cell culture
      system in male rats. Administration of PRL (10(-7) and 10(-6) M) resulted in dose
      dependent increases in corticosterone and progesterone release. Cotreatment with
      PRL produced an increase in the stimulatory effects of ACTH-induced
      corticosterone and progesterone secretion. However, the PRL-induced
      corticosterone and progesterone releases were significantly reduced by treatment
      with AG490, a specific Janus kinase 2 (Jak2) inhibitor. In addition,
      administration of AG490 blunted the significant inhibition of ACTH-induced
      corticosterone and progesterone secretion by PRL. These results demonstrated that
      PRL could act directly on the adrenal gland to drive corticosterone and
      progesterone secretion in male rats. Additionally, the results emphasize that PRL
      stimulation of adrenal steroid release may be mediated through Jak2 activity.

PMID- 17519523
TI  - Macro- and microstructure of the superior cervical ganglion in dogs, cats and
      horses during maturation.
AB  - The superior cervical ganglion (SCG) provides sympathetic input to the head and
      neck, its relation with mandible, submandibular glands, eyes (second and third
      order control) and pineal gland being demonstrated in laboratory animals. In
      addition, the SCG's role in some neuropathies can be clearly seen in Horner's
      syndrome. In spite of several studies published involving rats and mice, there is
      little morphological descriptive and comparative data of SCG from large mammals.
      Thus, we investigated the SCG's macro- and microstructural organization in medium
      (dogs and cats) and large animals (horses) during a very specific period of the
      post-natal development, namely maturation (from young to adults). The SCG of
      dogs, cats and horses were spindle shaped and located deeply into the bifurcation
      of the common carotid artery, close to the distal vagus ganglion and more related
      to the internal carotid artery in dogs and horses, and to the occipital artery in
      cats. As to macromorphometrical data, that is ganglion length, there was a 23.6%
      increase from young to adult dogs, a 1.8% increase from young to adult cats and
      finally a 34% increase from young to adult horses. Histologically, the SCG's
      microstructure was quite similar between young and adult animals and among the 3
      species. The SCG was divided into distinct compartments (ganglion units) by
      capsular septa of connective tissue. Inside each ganglion unit the most prominent
      cellular elements were ganglion neurons, glial cells and small intensely
      fluorescent cells, comprising the ganglion's morphological triad. Given this
      morphological arrangement, that is a summation of all ganglion units, SCG from
      dogs, cats and horses are better characterized as a ganglion complex rather than
      following the classical ganglion concept. During maturation (from young to
      adults) there was a 32.7% increase in the SCG's connective capsule in dogs, a
      25.8% increase in cats and a 33.2% increase in horses. There was an age-related
      increase in the neuronal profile size in the SCG from young to adult animals,
      that is a 1.6-fold, 1.9-fold and 1.6-fold increase in dogs, cats and horses,
      respectively. On the other hand, there was an age-related decrease in the nuclear
      profile size of SCG neurons from young to adult animals (0.9-fold, 0.7-fold and
      0.8-fold in dogs, cats and horses, respectively). Ganglion connective capsule is
      composed of 2 or 3 layers of collagen fibres in juxtaposition and, as observed in
      light microscopy and independently of the animal's age, ganglion neurons were
      organised in ganglionic units containing the same morphological triad seen in
      light microscopy.

PMID- 17519524
TI  - Effects of partial ablation of the cerebellum on sustained swimming in goldfish.
AB  - To investigate the role of the corpus cerebelli in the control of sustained
      swimming or cruising in goldfish, Carassius auratus, we conducted experiments
      examining the effects of partial ablation of the corpus cerebelli (CC) on
      swimming performance against constant water flow at various speeds. Ten out of 15
      CC-ablated fish successfully maintained sustained swimming against water flow
      even at the highest speed tested (3.0 body lengths per second). This result
      showed that the CC is not crucial for generating the simple swimming motor
      pattern, although some effects of the surgical operation itself on the capability
      of the sustained swimming were found in both sham-operated and CC-ablated fish.
      However, we found that both tail-beat amplitude and frequency in CC-ablated
      goldfish tended to be greater than that of control fish at the same swimming
      speeds. The thrust index (square of the value obtained by multiplying the tail
      beat frequency (Hz) by twice the tail beat amplitude (mm)) was significantly
      larger in CC-ablated fish than in control fish at higher swimming speeds (> or
      =2.0 body length per second). This result suggests that CC-ablated goldfish
      produced more thrust by tail beats than control fish to maintain sustained
      swimming at higher speeds. We concluded that in goldfish the CC plays no major
      role in the posture control and generation of simple forward swimming movement,
      although the integrity of the CC is important for execution of normal swim gait.

PMID- 17519525
TI  - Central projections of sensory systems involved in honey bee dance language
      communication.
AB  - Honey bee dance language is a unique and complex form of animal communication
      used to inform nest mates in the colony about the specific location of food
      sources or new nest sites. Five different sensory systems have been implicated in
      acquiring and communicating the information necessary for dance language
      communication. We present results from neuronal tracer studies identifying the
      central projections from four of the five. Sensory neurons of the dorsal rim area
      of the compound eyes, involved in acquiring sun-compass based information,
      project to the dorsal-most part of the medulla. Sensory neurons of the neck hair
      plates, required to transpose sun-compass based information to gravity-based
      information in the dark hive, project to the dorsal labial neuromere of the
      subesophageal ganglion. Sensory neurons from the antennal joint hair sensilla and
      the Johnston's organ, which perceive information on dance direction and distance
      from mechanostimuli generated by abdomen waggling and wing vibration, project to
      the deutocerebral dorsal lobe and the subesophageal ganglion, and the posterior
      protocerebrum, respectively. We found no 'dance-specific' projections relative to
      those previously described for drone and queen honey bees and other insect
      species that do not exhibit dance communication. We suggest that the evolution of
      dance language communication was likely based on the modification of central
      neural pathways associated with path integration, the capability to calculate
      distance, and directional information during flight.

PMID- 17519526
TI  - Mushroom body volume is related to social aggression and ovary development in the
      paperwasp Polistes instabilis.
AB  - The mushroom bodies (MB) are a complex neuropil in insect brains that have been
      implicated in higher-order information processing such as sensory integration and
      various types of learning and memory. Eusocial insects are excellent models to
      test functional neural plasticity in the MB because genetically related nest
      mates differ in task performance, environmental experience and social
      interactions. Previous research on eusocial insects shows that experience
      dependent changes in brain anatomy (i.e., enlarged MB calyces) are positively
      correlated with task performance and social interactions. In this study, we
      quantified relationships of task performance and social and reproductive
      dominance with MB volume in Polistes instabilis, a primitively eusocial paper
      wasp. We used experimental removals of dominant workers to induce changes in
      aggressive behavior and foraging by workers. Ovary development and social
      dominance were positively associated with the volume of the MB calyces relative
      to the region containing the Kenyon cell bodies. In contrast to highly eusocial
      insect workers, foraging behavior was not positively correlated with MB calycal
      volume. We conclude that mushroom body volume is more strongly associated with
      dominance rank than with foraging behavior in Polistes instabilis.

PMID- 17519527
TI  - Gastric electrical stimulation is safe and effective: a long-term study in
      patients with drug-refractory gastroparesis in three regional centers.
AB  - BACKGROUND: Drug-refractory gastroparesis has previously been without acceptable
      alternative therapies. Although gastric electrical stimulation has been used for
      over a decade, no long-term multicenter data exist. METHODS: We studied 214
      consecutive drug-refractory patients with the symptoms of gastroparesis (146
      idiopathic, 45 diabetic, 23 after surgery) who consented to participate in a
      variety of clinical research and clinical protocols at three centers from January
      1992 through January 2005, resulting in 156 patients implanted with a gastric
      electrical stimulation device and the other 58 patients serving as controls. The
      patients were stratified into three groups: (1) consented but never permanently
      implanted; (2) implanted with permanent device, and (3) consented while awaiting
      a permanent device. The patients were followed over time for gastrointestinal
      symptoms, solid gastric emptying, health-related quality of life, survival,
      device retention, and complications. Demographics, descriptive statistics, and t
      tests were used for comparison between baseline and latest follow-up. RESULTS: At
      latest follow-up, median 4 years for 5,568 patient months, most patients
      implanted (135 of 156) were alive with intact devices, significantly reduced
      gastrointestinal symptoms, and improved health-related quality of life, with
      evidence of improved gastric emptying, and 90% of the patients had a response in
      at least 1 of 3 main symptoms. Most patients explanted, usually for pocket
      infections, were later reimplanted successfully. There were no deaths directly
      related to the device. CONCLUSION: Based on this sample of patients, implanted
      with gastric electrical stimulation devices at three centers and followed for up
      toward a decade, gastric electrical stimulation for drug-refractory gastroparesis
      is both safe and effective.

PMID- 17519528
TI  - Prognostic value of renal hemodynamic characteristics in patients with
      proliferative lupus nephritis.
AB  - BACKGROUND/AIM: Previous studies showed that renal hemodynamic parameters,
      especially the filtration fraction (FF), are decreased in patients with active
      lupus nephritis (LN). In this study, we evaluate the prognostic value of renal
      hemodynamic function tests on the renal outcome in patients with proliferative
      LN. METHODS: We performed a retrospective cohort study of our patients with
      proliferative LN from 1986 to 2005. Glomerular filtration rate (GFR) and FF
      before treatment were measured. Treatment failure was defined as a renal relapse
      or development of end-stage renal disease. RESULTS: Thirty-seven patients were
      included. The median follow-up period was 8 years. Creatinine clearance, GFR, and
      FF before treatment correlated with the creatinine clearance at the end of follow
      up (p = 0.001, p = 0.006, and p = 0.04, respectively). The FF was decreased in
      92% of our patients, but FF and GFR did not have a prognostic value with regard
      to treatment failure. CONCLUSIONS: Most patients with proliferative LN had a low
      FF. Low GFR and FF at baseline were correlated with a worse renal function at the
      end of follow-up, but this had no prognostic value in individual patients.

PMID- 17519529
TI  - Oligohydramnios decreases platelet-derived growth factor expression in fetal rat
      lungs.
AB  - OBJECTIVE: To evaluate the effects of experimental oligohydramnios on lung
      growth, expression of platelet-derived growth factor (PDGF) and its receptors,
      and lung morphology in fetal rats. METHODS: On day 16 of gestation, we
      anesthetized timed pregnant Sprague-Dawley dams and punctured uterine wall and
      fetal membranes of each uterine sac which resulted in oligohydramnios. The
      fetuses in the opposite uterine horn served as controls. On days 19 and 21 of
      gestation, the fetuses were delivered by cesarean section and weighed, and the
      lungs were dissected free and weighed. RESULTS: Rats exposed to oligohydramnios
      exhibited significantly lower lung/body weight ratios on days 19 and 21 of
      gestation and significantly lower radial saccular counts on day 21 of gestation
      than did the control rats. Lung PDGF-A and PDGF-B gene and protein expression and
      elastin level were significantly decreased in rats exposed to oligohydramnios on
      days 19 and 21 of gestation. The PDGF receptor alpha and beta gene expression
      levels were significantly decreased in rats exposed to oligohydramnios on day 19
      of gestation. CONCLUSION: A decreased PDGF expression may be important in the
      pathogenesis of oligohydramnios-induced pulmonary hypoplasia and suggests that
      supplementation may provide useful therapeutic strategies.

PMID- 17519530
TI  - Melatonin levels during the first week of life and their relation with the
      antioxidant response in the perinatal period.
AB  - AIM: Melatonin is a potent free radical scavenger and an indirect antioxidant.
      Knowledge about the behavior of melatonin secretion in the early neonatal period,
      which may relate to its properties at a vital stage during very high antioxidant
      demands, is limited. PATIENTS AND METHODS: We studied 35 newborns admitted to the
      Neonatal Unit with respiratory distress syndrome (RDS) and with no signs of
      sepsis, severe anemia, hemodynamic compromise or malformation. The gestational
      age of the newborns was 26-40 weeks (mean value 32.5 weeks) and the weight at
      birth was 870-4,400 g (mean value 1,800 g). They were classified into two groups:
      <or=1,500 g or >1,500 g birthweight. In all cases, at 09:00 h on their 1st, 3rd
      and 7th days of life, serum melatonin was measured by RIA. The clinical history
      was recorded and treatment and follow-up were performed according to established
      neonatology practice, and the resultant data recorded. Informed consent from the
      parents or guardians was obtained in accordance with the Declaration of Helsinki.
      Statistical analysis was carried out using ANOVA-II (factor I: day of sample;
      factor II: birthweight). RESULTS: There were significant increases in melatonin
      levels with increasing birthweight (p = 0.017), but no changes by day of sample.
      Although in both study groups melatonin levels increased during the first few
      days this was not statistically significant. CONCLUSIONS: In newborns of low
      birthweight, we report high melatonin concentrations in the morning and during
      the first week of life. These increase with maturation, and at full-term were
      similar to nocturnal levels during the acrophase of pineal gland secretion in
      toddlers and schoolage children, when pineal gland secretion is maximal and takes
      place reflecting environmental variations. In the early neonatal period these
      high levels of melatonin seem to derive from extrapineal sources, which mature to
      provide antioxidant protection in accordance with other elements of the
      antioxidant network to compensate for the high levels of oxidative stress that
      are present in the perinatal period.

PMID- 17519531
TI  - Effects of thiopental on Ca2+ currents and intracellular Ca2+ transient in single
      atrial cells from guinea pig.
AB  - The effects of thiopental on Ca2+ currents and intracellular Ca2+ transient in
      single atrial cells from guinea pigs were studied by means of a whole-cell
      voltage-clamp method and Ca2+-sensitive fluorescent dye. Thiopental inhibited L
      type voltage-dependent Ca2+ currents in a concentration-dependent manner
      (IC50=2.8.10(-5) mol/l). Moreover, the mode of Ca2+ current inhibition by
      thiopental showed no use dependency. Electrical stimulation-induced intracellular
      Ca2+ transient was significantly suppressed by 10(-5) mol/l thiopental. However,
      the caffeine-sensitive Ca2+ releasing pathway from sarcoplasmic reticulum was not
      affected by thiopental. Our results indicate that thiopental inhibits L-type Ca2+
      currents, but not release of Ca2+ from sarcoplasmic reticulum. These results
      suggest that the negative inotropic action of thiopental is mainly due to
      inhibition of L-type Ca2+ channels in guinea pig atrial myocytes.

PMID- 17519532
TI  - Brain natriuretic peptide reverses the effects of myocardial stunning in rabbit
      myocardium.
AB  - We tested the hypothesis that brain natriuretic peptide (BNP) would decrease the
      effects of myocardial stunning in rabbit hearts. We also examined the mechanisms
      responsible for these effects. In two groups of anesthetized open-chest rabbits,
      myocardial stunning was produced by 2 15-min occlusions of the left anterior
      descending artery separated by 15 min of reperfusion. The treatment group had BNP
      (10(-3) mol/l) topically applied to the stunned area. Hemodynamic and functional
      parameters were measured. Coronary flow and O2 extraction were used to determine
      myocardial O2 consumption. In separate animals, we measured the function of
      isolated control and simulated ischemia (95% N2/5% CO2, 15 min)-reperfusion
      ventricular myocytes with BNP or C-type natriuretic peptide (10(-8)-10(-7) mol/l)
      followed by KT5823 (10(-6) mol/l, cyclic GMP protein kinase inhibitor). In the in
      vivo control group, baseline delay to contraction was 47+/-4 ms and after
      stunning it increased to 71+/-10 ms. In the treatment group, baseline delay to
      contraction was 40+/-7 ms, and after stunning and BNP it did not significantly
      increase (43+/-6 ms). Neither stunning nor BNP administration affected regional
      O2 consumption. In control myocytes, BNP (10(-7) mol/l) decreased the percent
      shortening from 6.7+/-0.4 to 4.5+/-0.2%; after KT5823 administration, the percent
      shortening increased to 5.4+/-0.5%. In ischemia-reperfusion myocytes, BNP (10(-7)
      mol/l) decreased the percent shortening less from 5.0+/-0.5 to 3.8+/-0.2%; KT5823
      administration did not increase the percent shortening (3.8+/-0.2%). BNP
      similarly and significantly increased cyclic GMP levels in control and stunned
      myocytes. The data illustrated that BNP administration reversed the effects of
      stunning and its mechanism may be independent of the cyclic GMP protein kinase.

PMID- 17519533
TI  - Heterogeneous metastasis efficiency of isogenic orthotopic colon cancer
      xenografts reveals distinctive gene expression profiles.
AB  - Hepatic and lung metastases are the leading causes of mortality and major
      indicators of aggressiveness in colorectal cancer. The underlying molecular
      mechanisms contributing to the development of metastasis are still unclear. Here,
      we designed a novel approach to explore gene expression profiles associated with
      metastasis in human colorectal cancer (hCRC). A series of ten isogenic tumors
      from three different hCRC models were orthotopically implanted into nude mice. In
      these series, we analyzed the contribution of dynamic heterogeneity,
      independently of any intrinsic gene expression program predictive of metastasis.
      When screened for the presence of disseminated tumor cells in the lung and liver,
      as the most common host tissues for hCRC metastases, both high- and low
      metastatic efficient tumors were found among these isogenic orthotopic series.
      The metastasis-specific cDNA macroarray analysis of 96 genes, in both tumor
      populations for each of the three hCRC models, characterized a common
      differential gene expression within a small group of genes. Our results suggest
      that, independently of a gene expression profile predictive of metastasis, the
      progressive acquisition of additional alterations occurs during hCRC
      tumorigenesis. This dynamic process might determine tumor progression, namely the
      metastasis dissemination.

PMID- 17519534
TI  - Expression of the apoptosis inhibitor livin in renal cell carcinomas:
      correlations with pathology and outcome.
AB  - Livin has recently been identified as a member of the inhibitor of apoptosis
      family expressed in several types of cancer but not in most benign tissues.
      Expression levels of livin were associated with prognosis in various
      malignancies, but livin expression and its prognostic relevance have not been
      evaluated in renal cell carcinomas (RCC). In a cohort of 152 RCC patients, we
      analyzed the relative expression of livin and its splicing variants by real-time
      RT-PCR and Western blot in tumor and adjacent normal renal tissue specimens.
      Livin expression was detected in 59 (38.8%) of 152 RCC specimens but in none of
      the normal samples. Both splicing variants were present in the livin-positive RCC
      specimens. Livin expression levels did not correlate with pathological or
      clinical parameters and were not predictive of patient outcome. Our findings
      suggest that livin expression in RCC is not of prognostic relevance. Further
      studies to clarify the role of livin expression in RCC and its potential value as
      a target for immune-mediated tumor destruction are warranted.

PMID- 17519535
TI  - Expression of EphA2 in human astrocytic tumors: correlation with pathologic
      grade, proliferation and apoptosis.
AB  - A high expression of EphA2 has been detected in many non-central nervous system
      tumors; however, the EphA2 expression in brain astrocytic tumors remains unclear.
      In this study, we investigated the expression of EphA2 mRNA and protein in 90
      cases of human astrocytic tumors by reverse transcription polymerase chain
      reaction and immunohistochemistry, respectively. The proliferative index (PI) of
      tumor cells was evaluated by Ki-67 immunohistochemistry, and the apoptotic index
      (AI) was determined by TdT-mediated dUTP nick end labeling assay. The correlation
      between EphA2 expression, pathologic grade, proliferation and apoptosis of
      astrocytic tumors was further analyzed. The results showed that 47.8% of cases
      expressed EphA2 mRNA and 43.3% of cases expressed EphA2 protein. With increasing
      pathologic grade, the positive rate of EphA2 mRNA and protein, as well as the
      EphA2 immunoreactivity score (IRS), increased markedly. The PI in the EphA2
      positive group was significantly higher than in the EphA2-negative group. In
      addition, the PI was positively correlated with EphA2 IRS. Although there was no
      significant difference between the AI in the EphA2-positive group and that in the
      EphA2-negative group, the AI was inversely correlated with EphA2 IRS. Therefore,
      EphA2 may be a new biomarker for astrocytic tumors. It may also affect the
      proliferation and apoptosis of tumor cells and be an attractive therapy target
      for astrocytic tumors.

PMID- 17519536
TI  - KCl depolarization increases HIF-1 transcriptional activity via the calcium
      independent pathway in SGC7901 gastric cancer cells.
AB  - BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) has been reported to be
      expressed aberrantly in gastric cancer cells. Stability and transactivation of
      HIF-1 were associated with the change of intracellular calcium. We hypothesized
      that KCl depolarization may modulate HIF-1 activity in gastric cancer cells
      through calcium involvement. METHODS: HIF-1alpha expression and its
      transcriptional activity were determined in SGC7901 gastric cancer cells treated
      with KCl and/or CoCl2 under normoxia. KCl induced change in the intracellular
      free calcium concentration and its effect on HIF-1 activity was investigated
      subsequently. RESULTS: Exposure of SGC7901 cells to KCl (50 mM) could induce HIF
      1alpha expression and its nucleus accumulation under normoxic conditions,
      reaching the peak at 8 and 2 h, respectively. KCl could also induce
      transactivation of the HIF-1 reporter gene and its target gene VEGF secretion at
      8 h. Further experiments confirmed that depolarization of SGC7901 cells with KCl
      caused an increase in intracellular free calcium concentration. Chelation of
      intracellular calcium by BAPTA [1,2-bis (2-aminophenoxy) ethane-N,N,N',N'
      tetraacetic acid] induced HIF-1alpha accumulation and HIF-1 activity. However,
      elevation of cytosolic calcium level by ionomycin, a calcium ionophore, failed to
      induce HIF-1 transcriptional activity. CONCLUSIONS: KCl depolarization would act
      through the calcium-independent pathway leading to enhanced HIF-1 transcriptional
      activity in gastric cancer cells.

PMID- 17519537
TI  - Early renal injury after nonmyeloablative allogeneic peripheral blood stem cell
      transplantation in patients with chronic myelocytic leukemia.
AB  - BACKGROUND: Renal insufficiency is a common complication early after
      hematopoietic stem cell transplantation (HSCT). Over the past several years,
      significant advancement has been achieved in HSCT, especially in nonmyeloablative
      stem cell transplantation. Compared with traditional HSCT, nonmyeloablative HSCT
      employs significantly lower doses of chemoradiotherapy and lower toxicity. The
      current study evaluated renal insufficiency during the first 100 days in patients
      with chronic myelocytic leukemia (CML) who underwent nonmyeloablative allogeneic
      peripheral blood stem cell transplantation (allo-PBSCT) in a single center.
      METHODS: A total of 26 consecutive patients with CML received nonmyeloablative
      allo-PBSCT from 2002 to 2005 in Zhong Da Hospital. The average age of the
      patients was 40.2 +/- 8.2 years. Renal function was measured by serum creatinine
      concentration and estimated glomerular filtration rate (GFR) during the first 100
      days after nonmyeloablative allo-PBSCT. Renal dysfunction was classified as
      follows: grade 0 (<25% decline in GFR), grade 1 (> or =25% decrease in GFR but
      <twofold rising in serum creatinine), grade 2 (> or =twofold increase in serum
      creatinine but no need for dialysis) and grade 3 (> or =twofold increase in serum
      creatinine and need for dialysis). Acute renal failure (ARF) was defined as a
      doubling of baseline serum creatinine, grade 2 and grade 3. RESULTS: All the
      patients were successfully engrafted. Of the 26 patients, 10 (38%) patients had
      some degree of renal dysfunction (grade 1, 5 patients; grade 2, 4 patients; grade
      3, 1 patient). They developed ARF at an average of 32.8 +/- 4.0 days after
      transplantation. No significant difference was observed in terms of age, baseline
      serum creatinine, albumin and hemoglobin between the patients with ARF and
      without ARF. Renal dysfunction was associated with significantly higher
      frequencies of sepsis and hepatic veno-occlusive disease (VOD, p < 0.01,
      respectively). The overall mortality rate at the end of 100 days was 19% (5/26).
      The mortality rate for patients with ARF was significantly higher than those
      without ARF (p < 0.001). CONCLUSION: During the first 100 days following
      nonmyeloablative allo-PBSCT in patients with CML, a 38% incidence of renal
      dysfunction and a 19% of ARF were found, which were much less than previous
      studies. Sepsis and VOD were significantly correlated with the development of
      renal dysfunction. Severe nephrotoxicity was associated with the increase in
      mortality.

PMID- 17519538
TI  - Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute
      ischemic stroke: a review of the risk factors.
AB  - BACKGROUND: Symptomatic intracerebral hemorrhage (SICH) following thrombolytic
      therapy for acute ischemic stroke is associated with a high rate of morbidity and
      mortality. Knowledge of the risk factors associated with SICH following
      thrombolyitc therapy may provide insight into the pathophysiological mechanisms
      underlying the development of SICH, lead to the development of treatments that
      reduce the risk of SICH and have implications for the design of future stroke
      trials. METHODS: Relevant studies were identified through a search in Pubmed.
      Included studies used multivariate analyses to identify independent risk factors
      for SICH following thrombolytic therapy. For each variable that was found to have
      a significant association with SICH, a secondary literature search was conducted
      to identify additional reports on the specific relationship between that variable
      and SICH. SUMMARY OF REVIEW: Twelve studies met inclusion criteria for the
      systematic review. Extent of hypoattenuated brain parenchyma on pretreatment CT
      and elevated serum glucose or history of diabetes were independent risk factors
      for thrombolysis-associated SICH in six of the twelve studies. Symptom severity
      was an independent risk factor in three of the studies and advanced age,
      increased time to treatment, high systolic blood pressure, low platelets, history
      of congestive heart failure and low plasminogen activator inhibitor levels were
      found to be independent risk factors for SICH in a single study. Although these
      data should not alter the current guidelines for the use of rt-PA in acute
      stroke, they may help develop future strategies aimed at reducing the rate of
      thrombolysis-associated SICH.

PMID- 17519539
TI  - Patterns of infarction in hemodynamic failure.
AB  - BACKGROUND AND PURPOSE: The mechanism of stroke in patients with atherosclerotic
      occlusive disease and hemodynamic failure may be primarily hemodynamic or a
      combination of hemodynamic and embolic factors. The purpose of this study was to
      investigate the clinical and imaging features of stroke in these patients.
      METHODS: Eleven patients with complete atherosclerotic carotid artery occlusion
      and increased oxygen extraction fraction measured in the hemisphere distal to the
      occlusion developed an ischemic stroke during the observation phase of a
      prospective study of cerebral hemodynamics and stroke risk. The medical and study
      records related to the endpoint event for these 11 patients were reviewed.
      Records were reviewed for evidence of associated hypotension and for specific
      details of the neurological deficit. Infarct location was characterized, based on
      review of imaging and clinical features, as: (1) middle cerebral artery (MCA)
      core; (2) possible cortical border zone, or (3) internal border zone. RESULTS:
      One patient had a retinal infarction; the remaining 10 had MCA territory strokes.
      Six of the 10 infarctions occurred in the MCA core territory. Two of these 6 were
      fatal hemispheric events. One of the 10 infarctions occurred in the cortical
      border zone region. Two of the remaining 3 infarctions were localized to the
      internal border zone. One was indeterminate. CONCLUSIONS: The clinical features
      and radiological patterns of stroke in many patients with hemodynamic impairment
      failure and carotid occlusion are most consistent with large artery
      thromboembolic stroke. These data suggest a synergistic effect between embolic
      and hemodynamic mechanisms for large artery thromboembolic stroke.

PMID- 17519540
TI  - Carotid artery calcification on multislice detector-row computed tomography.
AB  - BACKGROUND: To determine the underlying conditions that affect the degree of
      calcification of carotid arterial plaques, measured quantitatively using
      multidetector row computed tomography (MDCT), and to study the association of
      carotid calcification with clinical symptomatology. METHODS: We measured the
      calcification volume of stenotic lesions at the carotid bifurcation using MDCT in
      84 consecutive patients who were scheduled to undergo carotid revascularization.
      These results were compared with the clinical and radiological characteristics of
      the patients. RESULTS: On MDCT, calcification in the carotid plaques was present
      in 78 patients (93%). Compared to the other patients, patients in the highest
      quartile of calcification volume (quartile 4) had higher serum creatinine levels
      (p < 0.001) and tended to have fewer symptomatic ischemic events in the territory
      of the affected carotid artery in the preceding 6 months (29 vs. 49%, p = 0.099);
      in particular, there were fewer transient symptoms (5 vs. 27%, p = 0.032) and
      symptoms possibly occurring due to local embolism (14 vs. 37%, p = 0.045). On
      ultrasound, plaque ulceration was less prevalent in patients in quartile 4 than
      in the remaining patients (5 vs. 29%, p = 0.026), although the severity of
      carotid stenosis was similar among all the quartiles. CONCLUSIONS: Renal
      dysfunction was associated with enhanced carotid plaque calcification. Patients
      with severe carotid calcification were found to have a low risk of recent
      ischemic stroke, presumably due, in part, to a lower prevalence of emboligenic
      carotid ulceration. MDCT was valuable for the quantitative evaluation of carotid
      calcification.

PMID- 17519541
TI  - Does long-term continuous transcranial Doppler monitoring require a pause for
      safer use?
AB  - BACKGROUND: Transcranial Doppler sonography (TCD) has been used widely for long
      term monitoring of cerebral blood flow without adverse reports. However,
      attention has not been adequately paid to the fact that an increase in the time
      period of TCD insonation causes brain temperature to rise due to ultrasound
      absorption by tissue and the skull. We measured the actual temperature rise in
      local brain tissue induced by TCD insonation over a long time period during in
      vivo animal experiments in order to verify whether or not a pause is required in
      long-term, continuous TCD monitoring. METHODS: We inserted thermocouples into the
      skull-brain interface (SBI) of 15 New Zealand White rabbits (10: TCD application
      group; 5: control group, TCD non-application group). The TCD probe was placed on
      the parietal bone, and changes in SBI temperature (SBIT) were measured for 90
      min. TCD was set at maximum output level (0.2 W, 2 MHz). RESULTS: SBIT in the TCD
      group increased rapidly to 3.47 degrees C within 25 min and then reached a
      plateau. The maximum time for safe continuous TCD application is estimated to be
      33 min. CONCLUSIONS: Even though there are large differences in factors, such as
      brain volume and environmental conditions, between rabbits and humans, there is
      less difference in their cerebral blood flow per brain weight, which is the
      parameter that is mainly associated with heat reduction. Accordingly, the
      findings of the present experiment suggest that long-term TCD monitoring in
      clinical use should include a pause after every 30 min of insonation to avoid
      thermal damage to the brain surface.

PMID- 17519542
TI  - Carotid intima-media thickness and risk of cardiovascular events in high-risk
      patients. Results of the Osaka Follow-Up Study for Carotid Atherosclerosis 2
      (OSACA2 Study).
AB  - BACKGROUND AND PURPOSE: There is epidemiological evidence that increased carotid
      intima-media thickness (IMT) is a predictor of cardiovascular disease (CVD)
      events. However, the significance of carotid IMT in high-risk patients in whom
      risk factors are managed clinically has not been adequately investigated. The
      purpose of this study was to determine the usefulness of carotid IMT measurement
      in such patients. METHODS: The study comprised 900 outpatients with
      cardiovascular risk factors or established atherosclerosis. Carotid IMT was
      calculated as the mean bilateral IMT of the common carotid artery, bifurcation,
      and internal carotid artery. Baseline vascular risk factors, medications, and
      history of CVD were recorded at the time of enrollment. The incidence of CVD
      events was determined prospectively. RESULTS: During a mean follow-up period of
      2.6 years, there were 64 CVD events. The relative risk (RR) of a CVD event
      increased with increased IMT. Association between CVD events and carotid IMT was
      significant after adjustment for risk factors and history of CVD, showing an
      increased risk per IMT tertile from the middle tertile (RR, 2.5; 95% confidence
      interval [CI]: 1.0-6.3) to the highest (RR, 3.6; 95% CI: 1.4-9.0). When patients
      with a history of CVD were excluded (n = 574), the predictive value of IMT was
      significant even after adjustment for risk factors (hazard ratio per 1 SD IMT
      increase was 1.57 [95% CI: 1.11-2.20]). CONCLUSIONS: Carotid IMT is an
      independent predictor of vascular events in high-risk patients in whom risk
      factors are managed clinically.

PMID- 17519543
TI  - Variable platelet response to aspirin in patients with ischemic stroke.
AB  - BACKGROUND: A large number of patients experience ischemic stroke despite
      treatment with aspirin (acetylsalicylic acid, ASA). It is not clear whether all
      of these patients with ischemic stroke respond normally to ASA or are
      hyporesponsive as assessed by inhibition of aggregation and thromboxane (TX)
      synthesis. METHODS: We studied the effect of ASA given orally and ASA in vitro on
      collagen- and arachidonic-acid-induced TX formation and aggregation in platelet
      rich plasma of 90 patients with ischemic stroke and 25 healthy control subjects.
      RESULTS: Thirty-seven patients were being treated with ASA at the time of stroke.
      Arachidonic-acid-induced TX formation was not depressed below a predefined
      threshold of 25 ng/ml in 9 patients. Eight of these however exhibited a normal
      platelet sensitivity to ASA in vitro, suggesting poor compliance or a
      pharmacokinetic mechanism of nonresponse. The addition of ASA in vitro did not
      inhibit arachidonic-acid-induced TX formation below the above threshold in 6
      patients (11%) in the group of 53 stroke patients not receiving oral ASA,
      indicating an impaired response to ASA at the platelet level. Moreover, platelets
      from stroke patients showed an increased collagen-induced, TX-independent
      aggregation as compared with those of healthy individuals. CONCLUSION: Different
      categories of ASA nonresponders can be distinguished in patients with ischemic
      stroke. These include patients with poor bioavailability or noncompliance, an
      impaired platelet response to ASA in vitro and an increased, TX-independent
      hyperreactivity to collagen.

PMID- 17519544
TI  - Searching for subtle features of laxity of connective tissue in patients with
      ruptured intracranial aneurysms: a pilot study.
AB  - BACKGROUND: A disruption of the extracellular matrix (ECM) of the intracranial
      arterial wall is a likely contributing factor in the pathogenesis of intracranial
      aneurysms. If this is a generalized process, patients with subarachnoid
      haemorrhage (SAH) may have subtle signs of a general laxity of the connective
      tissue. We performed a pilot study to assess general laxity in SAH patients and
      to examine which tests for joint mobility can be best used in these patients.
      METHODS: In 59 SAH patients and sex- and age-matched controls we compared: (1)
      joint mobility (scores of Beighton and Bulbena and the total range of joint
      motion); (2) skin extensibility, and (3) bone quantity and stiffness. For the
      analyses we used the independent-samples T test and linear regression with
      adjustment for possible confounders. RESULTS: The patients had a higher degree of
      joint mobility according to the Beighton criteria (total score of 4 in patients
      vs. 2 in controls, p = 0.001) and the summation of Z scores of active range of
      motion measurements (0.1 in patients vs. -0.1 in controls, p = 0.0036), and a
      tendency towards a higher degree of joint mobility according to the Bulbena
      criteria (total score of 3 in patients vs. 2 in controls, p = 0.097) and the
      summation of active range of joint motion measurements (1,292 in patients vs.
      1,275 in controls, p = 0.13). No differences were found for the other
      investigated characteristics. CONCLUSIONS: Our preliminary results suggest that
      SAH patients have a higher degree of joint mobility than controls. The Beighton
      score can be best used in our patient population.

PMID- 17519545
TI  - The Cologne stroke experience: safety and outcome in 450 patients treated with
      intravenous thrombolysis.
AB  - BACKGROUND: Predictors of outcome and safety in intravenous thrombolysis within 3
      h in clinical routine is a matter of ongoing debate. Available reports contain
      small patient numbers or summarize heterogeneous multicenter data. METHODS: Four
      hundred and fifty patients received intravenous thrombolysis within 3 h after
      stroke. Pretreatment NIHSS score and detailed medical history were analyzed.
      Noncontrast CT was performed before thrombolysis, 24-36 h later and in case of
      clinical deterioration. Symptomatic intracranial hemorrhage (SICH; any bleeding
      with an NIHSS increase of > or =4 points) and clinical outcome (modified Rankin
      Scale, mRS) after 3 months were recorded. Logistic regression identified
      parameters predictive of independence (mRS 0-2) and SICH. RESULTS: Median onset
      to admission, door to needle and onset to treatment time was 75, 50 and 135 min,
      respectively. Direct presentation by emergency service (64%) was the fastest way
      of referral. Median pretreatment NIHSS was 11 points. Independence (mRS 0-2) was
      reached by 53%. Mortality was 11% (7% intracerebral, 4% extracerebral
      complications). Logistic regression identified low NIHSS, low age and absent
      diabetes as predictors of independence. Overall hemorrhagic complications and
      SICH were found in 18 and 4% of the patients, respectively. Extracerebral
      bleeding complications and allergic reactions were found in 3 and 1%,
      respectively. CONCLUSION: This largest single center report presents a sample in
      the range of the 3 h rt-PA cohort of all randomized controlled trials. Outcome
      was comparable to randomized studies with a higher rate of independence and a
      lower rate of mortality and SICH.

PMID- 17519546
TI  - Description of quality of life and its predictors in patients with aneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND: According to previous studies, the quality of life is usually
      substantially altered in patients who have suffered a subarachnoid hemorrhage of
      an aneurysmal origin. Some studies have attempted to find out which factors
      predict the deterioration in quality of life. Our study will try to describe the
      quality of life of these patients and discover which variables may predict it in
      each of its dimensions. METHODS: The participants were 70 patients with
      aneurysmal subarachnoid hemorrhage between 15 and 85 years of age. The instrument
      used to measure the quality of life is the SF-36 with its eight dimensions. The
      predictor variables introduced into the multiple linear regressions are
      neurological condition on admission [World Federation of Neurological Surgeons
      (WFNS) scale and Hunt and Hess scale], extension of the hemorrhage (Fisher
      scale), sex, age, physical handicaps, and the Glasgow Outcome Scale (GOS) on
      release. RESULTS: The results showed that 42.9% of the patients had a
      deteriorated quality of life after 4 months, and that the most affected dimension
      was the Physical Role (60%). The two factors that predict quality of life are sex
      and physical handicaps. Other factors that intervene are the GOS on release and
      the WFNS. CONCLUSIONS: The patients who have experienced an aneurysmal
      subarachnoid hemorrhage show greater difficulty in performing daily activities,
      and they present more depression and anxiety. The absence of handicaps and being
      male are predictor factors for an unaffected quality of life.

PMID- 17519547
TI  - Recognition of depression in aphasic stroke patients.
AB  - BACKGROUND: Data on post-stroke depression in aphasia are scarce. METHODS: Eighty
      nine acute stroke patients with aphasia of all types were followed for 6 months
      to investigate if depression can be reliably diagnosed (DSM-IV criteria) and
      validly assessed by the verbal Montgomery-Asberg Depression Rating Scale (MADRS)
      and a global technique (Clinical Global Impressions Rating Scale for Severity). A
      standard aphasia test was performed. RESULTS: In 60 patients (67%) at baseline
      and in 100% at 6 months, comprehension allowed a reliable DSM-IV diagnosis. Among
      these patients MADRS was feasible in 95% at baseline and in 100% at 6 months. The
      assistance of relatives and staff increases the feasibility and decreases the
      validity. Depression was identified in 24% during the 6 months. CONCLUSION:
      Depression diagnosis and severity rating can reliably be made in the acute phase
      in at least two thirds of aphasic patients, and feasibility increases over time.

PMID- 17519548
TI  - Management and outcome of patients with transient ischemic attack admitted to a
      stroke unit.
AB  - BACKGROUND: The way in which patients with transient ischemic attack (TIA) are
      investigated and treated varies substantially worldwide. There are no data on the
      management and outcome of TIA patients admitted to a stroke unit. We assessed to
      what extent rapid management of TIA patients admitted to a stroke unit led to
      specific treatments which can prevent stroke and evaluated the early risk and
      predictors of stroke in these patients. METHODS: From January 2003 to November
      2005, 203 consecutive patients with a recent (<48 h) TIA were admitted to our
      stroke unit. All patients had a diffusion-weighted imaging (DWI) on admission, a
      standardized etiological workup, and were followed up to 3 months. RESULTS: The
      median (interquartile range) time from TIA onset to admission to the stroke unit
      was 12 h (5-25). DWI revealed acute lesions in 64 patients (32%). Of the 203
      patients, 147 (72%) were treated by antiplatelet therapy and 56 (28%) with high
      doses of heparin, soon after their admission. In addition, 7 patients (3%) had a
      carotid revascularization. The risk of stroke was 2.5% (95% CI, 0.3-4.7) at 1
      week, and 3.5% (1.0-6.1) at 3 months. In multivariate analysis, a score > or =5
      at the previously validated ABCD score (HR = 5.0; 1.0-25.8; p = 0.06) and the
      presence of DWI abnormalities (HR = 10.3; 1.2-86.7; p = 0.03) were independent
      predictors of stroke at 3 months. CONCLUSION: Early management of TIA in a stroke
      unit leads to specific treatments in a significant proportion of cases. The
      presence of acute lesions on DWI and the ABCD score predict the 3-month risk of
      stroke after TIA.

PMID- 17519549
TI  - Presence of acute ischaemic lesions on diffusion-weighted imaging is associated
      with clinical predictors of early risk of stroke after transient ischaemic
      attack.
AB  - BACKGROUND: Early risk of stroke after a transient ischaemic attack (TIA) can be
      reliably predicted with risk scores based on clinical features of the patient and
      the event, but it is unclear how these features correlate with findings on brain
      imaging and few studies have investigated this in the subacute phase. METHODS:
      Two hundred consecutive patients attending a specialist clinic underwent
      diffusion-weighted brain imaging (DWI) on the day of the clinic (> or =3 days
      after a TIA) and the presence of recent lesions (positive DWI) was related to the
      presence of clinical features associated with a high stroke risk and to 2
      validated risk scores (ABCD and California). RESULTS: Thirty-one patients (16%)
      had positive DWI. Increasing ABCD and California scores were associated with
      positive DWI (p = 0.02 for both) independent of the delay from TIA to scan.
      CONCLUSION: Presence of recent ischaemic lesions on DWI correlates with validated
      clinical scores for risk of stroke after TIA in patients scanned subacutely.
      Future prognostic studies of DWI after TIA should adjust for the risk scores to
      determine the independent predictive value of DWI and hence the likely role of
      DWI in refinements of the scores.

PMID- 17519550
TI  - Application of neuroendoscopy in the treatment of intraventricular hemorrhage.
AB  - BACKGROUND: Spontaneous intraventricular hemorrhage is an infrequent but severe
      complication of hemorrhagic stroke. The conventional treatment of
      intraventricular hemorrhage consists of ventricular drainage or surgical
      evacuation, but neither of them is encouraged. The objective of this article is
      to compare different surgical procedures in order to evaluate a method of
      minimally invasive treatment for intraventricular hemorrhage. METHODS:
      Neuroendoscopy was applied to treat 22 cases of intraventricular hemorrhage.
      Twenty cases of the same disease that were treated by external ventricular
      drainage were taken as a control and comparison. RESULTS: All patients were
      followed up for 2 months. In the neuroendoscopy group, according to the Glasgow
      outcome scale, the result was excellent in 5 cases, good in 9, fair in 4, poor in
      2 and death in 2. In the external ventricular drainage group, the result was
      excellent in 1 case, good in 5, fair in 7, poor in 5 and death in 2. More
      patients in the neuroendoscopy group showed good recovery after 2 months of
      surgery (p < 0.05). The difference in mortality rate between the 2 groups was not
      statistically significant (p > 0.05). CONCLUSIONS: Neuroendoscopic neurosurgery
      for intraventricular hemorrhage offers better surgical treatment because it is
      characterized by visualized manipulation, effective hemorrhage evacuation and
      excellent postoperative outcomes.

PMID- 17519551
TI  - Trends in risk factors, patterns and causes in hospitalized strokes over 25
      years: The Lausanne Stroke Registry.
AB  - BACKGROUND AND OBJECTIVE: The Lausanne Stroke Registry includes, from 1979, all
      patients admitted to the department of Neurology of the Lausanne University
      Hospital with the diagnosis of first clinical stroke. Using the Lausanne Stroke
      Registry, we aimed to determine trends in risk factors, causes, localization and
      inhospital mortality over 25 years in hospitalized stroke patients. METHODS: We
      assessed temporal trends in stroke patients characteristics through the following
      consecutive periods: 1979-1987, 1988-1995 and 1996-2003. Age-adjusted
      cardiovascular risk factors, etiologies, stroke localizations and mortality were
      compared between the three periods. RESULTS: Overall, 5,759 patients were
      included. Age was significantly different among the analyzed periods (p < 0.001),
      showing an increment in older patients throughout time. After adjustment for age,
      hypercholesterolemia increased (p < 0.001), as opposed to cigarette smoking (p <
      0.001), hypertension (p < 0.001) and diabetes and hyperglycemia (p < 0.001). In
      patients with ischemic strokes, there were significant changes in the
      distribution of causes with an increase in cardioembolic strokes (p < 0.001), and
      in the localization of strokes with an increase in entire middle cerebral artery
      (MCA) and posterior circulation strokes together with a decrease in superficial
      middle cerebral artery stroke (p < 0.001). In patients with hemorrhagic strokes,
      the thalamic localizations increased, whereas the proportion of striatocapsular
      hemorrhage decreased (p = 0.022). Except in the older patient group, the
      mortality rate decreased. CONCLUSIONS: This study shows major trends in the
      characteristics of stroke patients admitted to a department of neurology over a
      25-year time span, which may result from referral biases, development of acute
      stroke management and possibly from the evolution of cerebrovascular risk
      factors.

PMID- 17519552
TI  - The time course and determinants of temperature within the first 48 h after
      ischaemic stroke.
AB  - BACKGROUND AND PURPOSE: Previous research has attempted to analyze the
      relationship between post-stroke hyperthermia and prognosis. These analyses have
      been hindered by a lack of information about the time course and determinants of
      temperature change after stroke. METHODS: Serial temperatures were measured until
      48 h after ischaemic stroke in a prospectively recruited cohort. Potential
      determinants of temperature, including stroke severity [measured using the
      National Institutes of Health Stroke Scale (NIHSS)], infection and paracetamol
      use were recorded. Mixed-effects models were used to model serial temperature
      measurements over time, adjusted for significant determinants. RESULTS: In 155
      patients the mean temperature rose from 36.5 degrees C at the time of stroke to
      36.7 degrees C approximately 36 h later. The factors with significant
      multivariable associations with serial temperatures were: first- and second-order
      time components, infection, paracetamol administration and the interaction
      between stroke severity (NIHSS > or =6) and time (all p < 0.1). Patients with
      admission NIHSS > or =6 had a mean temperature rise of 0.35 degrees C during the
      first 36 h after stroke, compared with a rise of 0.17 degrees C in those with
      NIHSS < or =5. CONCLUSIONS: Temperature spontaneously rises during the first 36 h
      after stroke, particularly after severer stroke and in the presence of infection.

PMID- 17519553
TI  - Prevalence and risk factors of middle cerebral artery stenosis in asymptomatic
      residents in Rongqi County, Guangdong.
AB  - BACKGROUND: Intracranial atherosclerosis is the commonest vascular lesion for
      ischemic stroke in Asians. Most research on risk factors for middle cerebral
      artery (MCA) stenosis has been conducted in symptomatic patients with ischemic
      stroke or transient ischemic attack. The present study aimed to investigate risk
      factors for MCA stenosis in an asymptomatic population in Rongqi County in
      Southern China. METHODS: We assessed 1,068 asymptomatic subjects over 50 years of
      age by transcranial Doppler. Medical history documentation and investigation of
      biochemical markers were performed for each subject. Multivariant, unconditioned,
      logistic regression analyses were employed to assess the risk factors associated
      with MCA stenosis. RESULTS: MCA stenosis was found in 63 subjects (5.9%). Male
      gender, advancing age, hypertension, diabetes and systolic blood pressure were
      significant risk factors for MCA stenosis (p < 0.001). Based on logistic
      regression analyses, 4 factors emerged as independent risk factors (p < 0.001) of
      MCA stenosis: male gender [95% confidence interval (CI) = 1.49-4.66, OR = 2.63],
      age (95% CI = 1.01-1.06, OR = 1.04), hypertension (95% CI = 4.57-18.35, OR =
      9.16) and diabetes mellitus (95% CI = 3.09-11.29, OR = 5.9). CONCLUSION: MCA
      stenosis is relatively common among asymptomatic Chinese subjects. Male gender,
      advanced age, hypertension and diabetes mellitus are risk factors for MCA
      stenosis.

PMID- 17519554
TI  - Taurine protects from liver injury after warm ischemia in rats: the role of
      kupffer cells.
AB  - BACKGROUND/AIMS: Warm ischemia to liver with subsequent Kupffer cell-dependent
      pathology is associated with many clinical conditions. Taurine prevents Kupffer
      cell activation and improves graft survival after experimental cold ischemia and
      liver transplantation. Thus this study was designed to assess its effects after
      warm hepatic ischemia. METHODS: The left liver lobe of female Sprague-Dawley rats
      (170-210 g) underwent 60 min of warm ischemia. Animals were given either
      intravenous taurine or Ringer's solution 10 min prior to warm ischemia.
      Transaminases, histology, in vivo microscopy, intercellular adhesion molecules-1
      (ICAM-1) expression, TNF-alpha and tissue hydroperoxide were compared between
      groups using analysis of variance (ANOVA) or ANOVA on ranks as appropriate.
      RESULTS: Taurine significantly decreased transaminases and improved histologic
      outcome. Phagocytosis of latex beads, serum TNF-alpha levels and tissue
      hydroperoxide concentrations were also significantly reduced. Stickers in
      sinusoids and post-sinusoidal venules significantly decreased. In parallel, both
      leukocyte infiltration and ICAM-1 expression decreased (p < 0.05), while flow
      velocity of red blood cells as well as sinusoidal perfusion rate were improved (p
      < 0.05). CONCLUSION: This study demonstrates that taurine blunts Kupffer cell
      dependent hepatic pathology after warm ischemia in vivo via mechanisms including
      leukocyte-endothelial interaction, microcirculation disturbances and protection
      against lipid peroxidation.

PMID- 17519555
TI  - Ethanol inhibitory effect on rat kidney brush border aminopeptidases.
AB  - BACKGROUND/AIM: Confusing data have been reported about the effect of ethanol or
      its metabolic products on blood pressure. The pressor agent, angiotensin II (Ang
      II), is found to be susceptible to degradation by different enzymes known as
      angiotensinases. We have studied the effects of ethanol and L-NAME, an inhibitor
      of nitric oxide synthase, consumption on rat serum and kidney ectoenzymes:
      aminopeptidase N (APN) and aminopeptidase A (APA). METHODS: Enzymatic activity of
      both enzymes was determined spectrophotometrically in serum and 10% homogenates
      of the rat kidney cortex using appropriate chromogenic substrates. RESULTS: After
      2 weeks of treatment with ethanol and L-NAME, blood urea and creatinine levels
      were significantly increased. The activities of APN (EC 3.4.11.2) and APA (EC
      3.4.11.7) were reduced in serum as well as in kidney tissue during this period. L
      NAME significantly attenuated activities of both enyzmes. Ethanol and L-NAME
      given simultaneously did not have an additional effect on the activity of
      investigated enzymes. CONCLUSION: Hypertension caused by chronic ethanol
      treatment as well as L-NAME administration could be associated with the reduction
      of APN and APA activity. Possible ethanol- and L-NAME-mediated inhibition of
      angiotensins degrading aminopeptidases could potentiate their effects on blood
      pressure.

PMID- 17519556
TI  - SM22alpha: the novel phenotype marker of injured glomerular epithelial cells in
      anti-glomerular basement membrane nephritis.
AB  - BACKGROUND/AIMS: Our previous comprehensive analysis of the genes expressed in
      kidneys with anti-glomerular basement membrane (GBM) nephritis using DNA
      microarrays showed that SM22alpha was one of the highly expressed genes.
      SM22alpha is a 22-kDa cytoskeletal protein that is exclusively expressed in
      smooth muscle cells. We investigated the localization of SM22alpha at mRNA and
      protein levels, and its pathological significance in anti-GBM nephritis kidneys.
      METHODS: Northern blot analysis, in situ hybridization, immunohistochemistry and
      double immunofluorescence studies were performed. The specific antibody (Ab)
      against SM22alpha was obtained by immunization of rabbits with recombinant rat
      SM22alpha protein. RESULTS: SM22alpha mRNA expression was upregulated in kidneys
      and inducibly expressed in the parietal and visceral glomerular epithelial cells
      in anti-GBM nephritis kidneys. Immunohistochemistry with anti-SM22alpha Ab showed
      that SM22alpha protein was localized in the same series of cells. Double
      immunofluorescence with anti-SM22alpha and anti-glomerular cell markers
      demonstrated that SM22alpha might be expressed in epithelial cells of injured
      glomeruli. In visceral epithelial cells, SM22alpha might be expressed in cells in
      which podocyte specific markers, podocalyxin and nephrin were lost. CONCLUSION:
      The injured glomerular epithelial cells in anti-GBM nephritis might undergo
      structural and functional alterations, including the expression of a smooth
      muscle marker, SM22alpha.

PMID- 17519557
TI  - Differences in renal tubule primary cilia length in a mouse model of Bardet-Biedl
      syndrome.
AB  - BACKGROUND: Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder that
      comprises numerous features, including renal cystic disease. Twelve BBS genes
      have been identified (BBS1-12). Although the exact functions of the BBS proteins
      are unknown, evidence suggests that they are involved in cilia assembly,
      maintenance and/or function. Renal primary cilia dysfunction can lead to cystic
      kidney disease. To test whether lacking Bbs4 affects cilia assembly and
      structure, we analyzed primary cilia in Bbs4-null (Bbs4(-/-)) mice. METHODS:
      Renal tubule cultures from wild-type (Bbs4(+/+)) and Bbs4(-/-) mice were examined
      by immunocytochemistry and scanning and transmission electron microscopy.
      RESULTS: Our culture conditions generated ciliated epithelial cells that were
      mostly of collecting duct origin. The microtubule ultrastructure of cilia and
      basal bodies did not appear disrupted in Bbs4(-/-) cells. In control cells, cilia
      length was maximal at 7 days in culture. In cells cultured from Bbs4(-/-) mice,
      cilia were shorter initially, but surpassed the length of control cilia by 10
      days. Renal primary cilia were also longer in Bbs4(-/-) kidneys. CONCLUSIONS:
      Lacking Bbs4 does not lead to aberrant cilia or basal body structure. However,
      the dynamics of cilia assembly is altered in Bbs4(-/-) cells, suggesting a role
      for Bbs4 in the regulation of ciliary assembly.

PMID- 17519558
TI  - Modification in the von Hippel-Lindau protein is involved in the progression of
      experimentally induced rat glomerulonephritis.
AB  - BACKGROUND/AIMS: We previously demonstrated that angiotensin II (AII) combined
      with Habu snake venom (HV) induces glomerulonephritis (GN) in rats, with lesions
      being restricted to the glomeruli 2 days after the administration of both
      reagents, but the mechanisms inducing GN are unclear. We also indicated a role
      for hypoxia-inducible factor (HIF)-1alpha in attenuating the progression of GN.
      However, a role of the von Hippel-Lindau (VHL) protein in GN and mechanisms by
      which HV regulates the pathogenesis of GN remains unclear. METHODS AND RESULTS:
      Immunohistochemical analysis revealed that VHL is weakly expressed in the renal
      tubules alone; however, HV caused elevated VHL expression in the injured
      glomeruli including endothelial cells and partially podocytes. Western blot
      analysis revealed that VHL expression was increased in HV-treated kidney compared
      with AII-treated or normal kidney. An in vitro study also showed HV-induced
      elevation in VHL expression. To investigate whether VHL pre-induction causes GN
      aggravation, we utilized thrombin, an inducer of VHL. Thrombin alone did not
      cause renal injuries; however, thrombin pre-treatment accelerated the development
      of GN even 1 day after treatment. CONCLUSION: We suggest that VHL pre-induction
      by thrombin aggravates GN, and that the increase in VHL expression due to HV
      might be involved in accelerating onset of GN.

PMID- 17519559
TI  - Behavioral evaluation of male and female mice pups exposed to fluoxetine during
      pregnancy and lactation.
AB  - BACKGROUND/AIMS: Fluoxetine (FLX) has been widely prescribed for depression
      during pregnancy and/or lactation. Since serotonin is a neurotrophic factor, the
      use of FLX by mothers could disrupt brain development resulting in behavioral
      alterations in their progeny. This study evaluated the effects of developmental
      FLX exposure on anxiety, depression, aggressivity and pain sensitivity of male
      and female mice pups. METHODS: Swiss dams were treated daily, by gavage, with 7.5
      mg/kg of FLX during pregnancy and lactation. Pups were submitted to open-field,
      forced swimming, elevated plus-maze, intruder-resident and hot plate tests at
      adolescence and adulthood. RESULTS AND CONCLUSION: In male pups, exposure to FLX
      decreased ambulation at postnatal day (PND) 40 and tended (p=0.07) to increase
      the latency to the first attack in the intruder-resident test at PND 70,
      suggesting decreased impulsivity. In female pups, FLX exposure increased
      immobility time in the forced swimming test at both PND 30 and 70, which is
      interpreted as depressive-like behavior. In conclusion, our results suggest that
      maternal exposure to FLX during pregnancy and lactation results in enduring
      behavioral alterations in male and female pups throughout life.

PMID- 17519560
TI  - In vivo assessment of Ectoin: a randomized, vehicle-controlled clinical trial.
AB  - The aim of the study was to assess an Ectoin formulation with regard to the
      antiageing properties. The study was designed as a monocentric, randomized,
      double-blind application test, in order to ensure the compatibility and the
      efficacy of Ectoin in comparison to a vehicle emulsion. A total of 104 voluntary
      healthy female test subjects were included in the study. Moisturizing properties
      as well as other parameters of skin ageing, like skin surface structure and skin
      elasticity, were determined for treatment A (vehicle) and treatment B (with 2%
      Ectoin) versus an untreated control. Statistical evaluations according to the
      Wilcoxon rank-sum test indicate a general preference for the Ectoin treatment by
      the test subjects in both the application and the efficacy tests. None of the
      participating test subjects had any side effects throughout the study. In terms
      of antiageing properties, previous in vitro studies could be confirmed by this
      clinical trial, clarifying that the natural cell protection concept of Ectoin is
      transferable to skin care with manifold benefits.

PMID- 17519561
TI  - Immunohistochemical study of osteopontin in boar testis.
AB  - The expression of osteopontin (OPN) in boar testis was studied. Western blot
      analysis detected 66- and 32-kDa OPN immunopositive bands in the testes of adult
      boars. In postnatal piglets, the 66-kDa OPN band was detected in the testes, but
      not the 32-kDa band. In the newborn testis, OPN immunostaining was seen in
      gonocytes and in some supporting cells in the seminiferous tubules, as well as in
      interstitial Leydig cells. In the adult boar testis, OPN immunoreactivity was
      detected in seminiferous tubules with varying intensities. Intense OPN
      immunostaining was seen in the residual bodies and acrosomes in the spermatids
      while, occasionally, OPN immunostaining was seen in spermatogonia and various
      stage of spermatocytes but in few Sertoli cells in the seminiferous tubules. In
      addition, Leydig cells in adult boars were weakly immunostained with OPN. These
      findings suggest that OPN is detected in the majority of germ cells and is
      involved in spermatogenesis in boar testis.

PMID- 17519562
TI  - Immunohistochemical expression of h-telomerase reverse transcriptase in canine
      and feline meningiomas.
AB  - Telomere length maintenance is regarded as a fundamental step in tumorigenesis,
      as most human brain tumors, including meningiomas, stabilize the ends of their
      chromosomes using telomerase. This investigation represents an introduction to
      telomerase expression in canine and feline meningiomas. Twenty-five archived
      cases (14 dogs and 11 cats) were immunohistochemically tested for human
      telomerase reverse transcriptase (h-TERT), scored, and quantified; furthermore,
      mitoses were counted on sections stained with a modified toluidine blue. The h
      TERT antibody immunolabelled the nucleus and nucleolus of meningeal neoplastic
      cells, with an intensity ranging from mild to strong and a speckled distribution;
      a significantly higher expression in cats was noted, while no significant
      association between h-TERT immunolabelling and sex or histotype was evident in
      dogs or cats. The telomerase enzyme represents a fundamental parameter of
      potential malignant transformation, which may occur independently of the signal
      to proliferate, thereby supplying the cells with unlimited growth capabilities.
      Telomerase expression could be a prognostic indicator independent of the kinetic
      parameters, although this should be evaluated using a larger dataset with
      available clinical information.

PMID- 17519563
TI  - The micronucleus frequency in cytokinesis-blocked lymphocytes of cattle in the
      vicinity of a nuclear power plant.
AB  - Cytogenetic and hematological analyses were performed on the peripheral blood
      lymphocytes (PBLs) obtained from Korean native cattle bred in the vicinity of
      three nuclear power plants (Wolsong, Uljin and Yeonggwang) and in a control area.
      The micronucleus (MN) rates for the cattle from the Wolsong, Uljin and Yeonggwang
      nuclear power plants and for the control area were 9.87 +/- 2.64, 8.90 +/- 3.84,
      9.20 +/- 3.68 and 9.60 +/- 3.91 per 1,000 cytokinesis-blocked lymphocytes,
      respectively. The apparent difference is not statistically significant. The MN
      frequencies of PBLs from cattle bred in the four areas are within the background
      variation for this study. The MN frequencies and hematological values were
      similar regardless of whether the cattle were bred near a nuclear power plant or
      in the control area.

PMID- 17519564
TI  - Epigallocatechin-3 gallate prevents cardiac hypertrophy induced by pressure
      overload in rats.
AB  - Pressure overload diseases, such as valvular stenosis and systemic hypertension,
      manifest morphologically in patients as cardiac concentric hypertrophy.
      Prevention of cardiac remodeling due to increased pressure overload is important
      to reduce morbidity and mortality. Epigallocatechin-3 gallate (EGCG) is a major
      bioactive polyphenol present in green tea which has been found to be a nitric
      oxide-mediated vasorelaxant and to be cardioprotective in myocardial ischemia
      reperfusion injury. Therefore, we investigated whether EGCG supplementation could
      reduce in vivo pressure overloadmediated cardiac hypertrophy. Cardiac hypertrophy
      was induced by suprarenal transverse abdominal aortic constriction (AC) in rats.
      Three weeks after AC surgery, heart to body weight ratio increased in the AC
      group by 34% compared to the sham group. EGCG administration suppressed the load
      induced increase in heart weight by 69%. Attenuation of cardiac hypertrophy by
      EGCG was associated with attenuation of the increase in myocyte cell size and
      fibrosis induced by aortic constriction. Despite abolition of hypertrophy by
      EGCG, transstenotic pressure gradients did not change. Echocardiogram revealed
      that increased left ventricular systolic dimensions and deteriorated systolic
      function were relieved by EGCG. These results suggest that EGCG prevents the
      development of left ventricular concentric hypertrophy by pressure overload and
      may be a useful therapeutic modality to prevent cardiac remodeling in patients
      with pressure overload myocardial diseases.

PMID- 17519565
TI  - Biological characteristics of Chinese hamster ovary cells transfected with bovine
      Prnp.
AB  - A normal prion protein (PrPc) is converted to a proteaseresistant isoform by an
      apparent self-propagating activity in transmissible spongiform encephalopathy, a
      neurodegenerative disease. The cDNA encoding open reading frame (ORF) of the
      bovine prion protein gene (Prnp) was cloned from Korean cattle by PCR, and was
      transfected into Chinese hamster ovary (CHO-K1) cells using lipofectamine. The
      gene expression of the cloned cDNA was confirmed by RT-PCR and Western blotting
      with the monoclonal antibody, 6H4. Cellular changes in the transfected CHO-K1
      cells were investigated using parameters such as MTT, lactate dehydrogenase
      (LDH), and superoxide dismutase (SOD) activities, as well as nitric oxide (NO)
      production, and an apoptosis assay. In the MTT and LDH assays, the bovine PrnP
      transfectant showed a lower proliferation rate than the wild-type (p < 0.05).
      Production of NO, after LPS or ConA stimulation, was not detected in either
      transfectants or CHO-K1 cells. In SOD assay under ConA stimulation, the SOD
      activity of transfectants was 10 times higher than that of CHO-K1 cells at 6 h
      after treatment (p < 0.05). The genomic DNA of both the transfectants and control
      cells began to be fragmented at 6 h after treatment with cyclohexamide. Caspase-3
      activity was reduced by transfection with the bovine Prnp (p < 0.05).
      Conclusively, the viability of transfectants expressing exogenous bovine Prnp was
      decreased while the capacities for cellular protection against antioxidative
      stress and apoptosis were increased.

PMID- 17519566
TI  - Diagnosis of Helicobacter spp. infection in canine stomach.
AB  - A total of 75 biopsied samples of cardia, fundus, body, and pyloric antrum from
      necropsied dogs that were submitted to the Department of Pathology, Faculty of
      Veterinary Science, Chulalongkorn University from April 2003 to June 2004 were
      investigated. The objectives of this study were to determine the prevalence of
      Helicobacter spp. in canine stomach by polymerase chain reaction (PCR) in
      comparison to histochemistry versus immunohistochemistry (IHC), and to correlate
      these diagnostic methods with the clinical significance in infected dogs.
      Histopathological results revealed 60.0% (45/75) of samples to be positive, and
      consisted of mild gastritis in 64.44% (29/45), moderate gastritis in 11.11%
      (5/45), and severe gastritis in 24.44% (11/45). The proportion showing no
      histopathological lesions was 40.0% (30/75). Helicobacter spp. were localized to
      the luminal crypt in 18.67% (14/75), gastric pit in 22.67% (17/75), gastric gland
      in 21.33% (16/75), and gastric epithelium in 8% (6/75). The percentages of
      positive samples of Helicobacter spp. diagnosed by hematoxylin and eosin stain
      (H&E), Warthin Starry stain (WSS), IHC with rabbit polyclonal anti-H. pylori
      antibody, and PCR were 17.3% (13/75), 46.7% (35/75), 30.7% (23/75), and 10.7%
      (8/75), respectively. No significant differences were observed in
      histopathological changes in portions of the stomach (p > 0.05). The diagnosis of
      Helicobacter spp. by PCR in comparison to that by WSS and IHC was not
      significantly different (p > 0.05). There were no relationships between
      pathological studies using H&E, WSS, and IHC, and especially between PCR and
      clinical signs of Helicobacter spp. infections in canine stomachs (p > 0.05). The
      present study revealed significantly different levels of correlation for
      Helicobacter spp. detection between H&E and WSS (p < 0.001). Results indicate
      that the method of choice for diagnosis of Helicobacter spp. infection in canine
      stomach is dependent on the purpose of study and appropriate specimen collection.

PMID- 17519567
TI  - Heterosporis anguillarum infections in farm cultured eels (Anguilla japonica) in
      Korea.
AB  - Ten eels (Anguilla japonica) from a fish farm in Korea were examined and
      diagnosed with a Heterosporis infection. The gross lesions on the trunk were
      uneven and the concave parts were pasty. Histopathologically, lyses of the trunk
      muscles, degenerative muscle fibers and the scattered spores were observed. The
      sporophorocyst (SPC) contained several spores with a variety of shapes. Some SPC
      were disrupted and the spores in the SPC were scattered in the muscle tissues.
      Macrophages existed near the scattered spores. Electron microscopy revealed
      special structures such as sporophorocyst containing various developmental
      parasitic stages such as meronts, sporonts, sporophorous vesicles and spores.

PMID- 17519568
TI  - PCR-based detection of genes encoding virulence determinants in Staphylococcus
      aureus from bovine subclinical mastitis cases.
AB  - The present study was carried out to genotypically characterize Staphylococcus
      aureus (S. aureus) isolated from bovine mastitis cases. A total of 37 strains of
      S. aureus were isolated during processing of 552 milk samples from 140 cows. The
      S. aureus strains were characterized phenotypically, and were further
      characterized genotypically by polymerase chain reaction using oligonucleotide
      primers that amplified genes encoding coagulase (coa), clumping factor (clfA),
      thermonuclease (nuc), enterotoxin A (entA), and the gene segments encoding the
      immunoglobulin G binding region and the X region of protein A gene spa. All of
      the isolates yielded an amplicon with a size of approximately 1,042 bp of the
      clfA gene. The amplification of the polymorphic spa gene segment encoding the
      immunoglobulin G binding region was observed in 34 isolates and X-region binding
      was detected in 26 isolates. Amplification of the coa gene yielded three
      different products in 20, 10, and 7 isolates. The amplification of the
      thermonuclease gene, nuc, was observed in 36 out of 37 isolates. All of the
      samples were negative for the entA gene. The phenotypic and genotypic findings of
      the present strategies might provide an understanding of the distribution of the
      prevalent S. aureus clones among bovine mastitis isolates, and might aid in the
      development of steps to control S. aureus infections in dairy herds.

PMID- 17519569
TI  - Dissemination and tracking of Salmonella spp. in integrated broiler operation.
AB  - Controlling Salmonella in integrated broiler operation is complicated because
      there are numerous potential sources of Salmonella contamination, including
      chicks, feed, rodents, wild poultry operations, and the processing plant. The
      objective of this study was to investigate the distribution of Salmonella through
      all phases of two integrated broiler operations and to determine the key areas
      related to the control of all known sources of infection. Two different
      Salmonella serotypes were observed at integrated broiler chicken company A. S.
      enteritidis, the predominant company A isolate, was consistently found in the
      breeder farm, hatcheries, broiler farms, and chicken slaughterhouse. At company
      B, a total of six different serotypes, S. heidelberg, S. senftenberg, S.
      enteritidis, S. blockley, S. gallinarum, and S. virchow, were detected. Although
      S. heidelberg was not found in the broiler farms, it was consistently found in
      the breeder farm, hatcheries, and chicken slaughterhouse. In addition, S.
      enteritidis was found in the hatcheries, broiler farm, and chicken
      slaughterhouse. In order to obtain the genetic clonality, 22 S. enteritidis
      isolates were digested with XbaI and analyzed by pulsed-field gel electrohporesis
      (PFGE). A difference in the PFGE pattern was found to be related to the origin of
      the integrated broiler operation. These data support the critical need to control
      Salmonella in breeder farms and hatcheries, and demonstrate important points
      related to the control of infection in large-scale poultry operations of Korea.

PMID- 17519570
TI  - Hematology, cytochemistry and ultrastructure of blood cells in fishing cat (Felis
      viverrina).
AB  - Hematological, cytochemical and ultrastructural features of blood cells in
      fishing cat (Felis viverrina) were evaluated using complete blood cell counts
      with routine and cytochemical blood stains, and scanning and transmission
      electron microscopy. No statistically significant difference was found in
      different genders of this animal. Unique features of blood cells in this animal
      were identified in hematological, cytochemical and ultrastructural studies. This
      study contributes to broaden hematological resources in wildlife animals and
      provides a guideline for identification of blood cells in the fishing cat.

PMID- 17519571
TI  - Suppressive effect of culture supernatant of erythrocytes and serum from dogs
      infected with Babesia gibsoni on the morphological maturation of canine
      reticulocytes in vitro.
AB  - The present study evaluated the effects of infected culture supernatant of
      erythrocytes, fractionation of culture supernatant and serum from dogs infected
      with Babesia gibsoni (B. gibsoni) on the maturation of canine reticulocytes in
      vitro. The SDS-PAGE demonstrated that significantly broader bands were generated
      by both the infected culture supernatant of erythrocytes and the serum from dogs
      chronically infected with B. gibsoni. The culture supernatant of erythrocytes
      infected with B. gibsoni strongly suppressed the maturation of reticulocytes.
      Prior studies showed that chronically infected serum had inhibitory effects on
      both the maturation of reticulocytes and the canine pyrimidine 5'-nucleotidase
      subclass I and purine-specific 5'-nucleotidase activity. In addition, serum free
      infected culture supernatant of erythrocytes had an inhibitory effect on the
      morphological maturation of reticulocytes. These results suggest that infected
      serum and culture supernatant of erythrocytes might accumulate excess proteins
      and/or metabolites as a result of the inhibited maturation of reticulocytes and
      decreased activity of erythrocyte 5'-nucleotidase. Furthermore, the fractions
      observed at >150 kDa- and 150-70 kDa- in the infected culture supernatant and
      serum retarded the maturation of canine reticulocytes in vitro. The results
      obtained from the in vitro examinations, in the present study, suggested that B.
      gibsoni itself and/or its metabolites might release certain proteins in the
      infected culture supernatant and serum from infected dogs and as a result delay
      morphological maturation of canine reticulocytes.

PMID- 17519572
TI  - Purification and characterization of two larval glycoproteins from the cattle
      tick, Boophilus annulatus.
AB  - The present study was conducted to identify new target immunogenic molecules from
      the larval stage of the cattle tick, Boophilus annulatus (Acari: Ixodidae). Two
      specific larval glycoproteins (GLPs) were isolated by two-step affinity
      chromatography. The larval immunogens were first purified with CNBr-Sepharose
      coupled to rabbit anti-larval immunoglobulins, and the glycoproteins were then
      purified with Con-A Sepharose. These glycoproteins have molecular weights of
      approximately 32 and 15 kDa with isoelectric points between 6.8 and 7.2.
      Antibodies against the two GLPs, labeled I and II, were detected in the anti
      whole tick, -whole larval, and -gut antigens through immunoblot analysis. These
      results suggest that these GLPs are good immunogens and can be useful in the
      vaccination of cattle against tick infestation.

PMID- 17519573
TI  - Successful introduction of modified dorsolumbar epidural anesthesia in a bovine
      referral center.
AB  - This study describes the successful use of modified dorsolumbar epidural
      anesthesia with a fixed volume of anesthetic in a bovine referral center. Among
      the 130 Holstein cattle scheduled for flank surgery, 90 cattle received a mixed
      anesthetic consisting of 1 ml of xylazine hydrochloride and 3 ml of lidocaine
      hydrochloride by modified dorsolumbar epidural anesthesia. Eighteen cattle with
      dehydration and/or lameness received a mixed anesthetic containing 0.5 ml of
      xylazine and 3 ml of lidocaine. Infiltration anesthesia was performed in 22
      cattle whose epidural space could not be reached in order to perform the flank
      surgery. The surgeries began about 12 min after the administration of the
      anesthetic and lasted for about 36 min. The modified method using a fixed volume
      of anesthetic was successfully introduced and effectively used in a bovine
      referral center. This modified method will allow veterinarians to save time and
      effort, thus lowering the cost of each surgery.

PMID- 17519574
TI  - Surgical treatment for different forms of hernias in sheep and goats.
AB  - Sheep and goats are frequently presented with different forms of hernias to
      veterinary clinics. The aim of this study is to investigate the outcome of the
      surgical treatment of abdominal, umbilical, inguinal and scrotal hernias in sheep
      and goats. Fifty-eight clinical cases (sheep = 44, goat = 14) were presented to
      the Veterinary Teaching Hospital, College of Agriculture and Veterinary Medicine,
      Qassim University, Saudi Arabia from September, 2003 to September, 2006. These
      animals had abdominal (sheep = 30, goat = 10), umbilical (sheep = 6, goat = 4),
      inguinal (sheep = 7) and scrotal (sheep = 1) hernias. All the cases of hernias in
      sheep and goats were subjected to full study including the history of the case,
      classification of hernias, the size of the hernial ring, surgical repair of the
      hernias, adhesions between the hernial sacs in each case, the postoperative care
      and follow up of the cases. The results revealed that gender had an effect on the
      incidence of hernia. The incidence of abdominal hernias was higher in females and
      the incidence of inguinal hernia was higher in males. There was a positive
      correlation between the history of hernia and the degree of adhesion. For the
      sheep, 26 out of 30 cases of abdominal hernia had good outcomes and the healing
      was excellent. There were postoperative complications in 4 ewes. For the goats,
      there were slight swellings at the site of operation in 2 out of 10 cases of
      abdominal hernia, while the remaining 8 cases had good outcomes. There was one
      case of umbilical hernia with an umbilical abscess that had broken down with
      sepsis formation at the surgical site. In conclusion, the success rates of
      surgical treatment for all types of hernias were very high and there were no
      significant differences in the success rates among the different types of hernias
      in both sheep and goats. The types of suture materials and the types of hernias
      had no significant effect on the outcome of the surgical treatment.

PMID- 17519575
TI  - Targeted surveillance to assess the presence of BSE in the age risk population of
      cattle slaughtered in Bursa, Turkey: preliminary results of an
      immunohistochemical detection study for the 2004-2005 period.
AB  - Bovine spongiform encephalopathy (BSE), a member of the transmissible spongiform
      encepahlopathies, has been a notifiable disease in Turkey since 1997. In 2002,
      the BSE status of Turkey was assessed by the EU Scientific Steering Committee as
      "it is likely but not confirmed". This study presents the results of a targeted
      surveillance study to assess the presence of BSE in the age risk population of
      Bursa, Turkey. In the assessment procedure, the immunohistochemical detection of
      protease-resistant prion protein (PrP-Sc) was aimed at and applied to 420 brain
      tissues of cattle slaughtered in Bursa at an age of 30-months and older. None of
      the samples were positive for BSE.

PMID- 17519576
TI  - The seroprevalence of Japanese encephalitis virus in goats raised in Korea.
AB  - Japanese encephalitis virus (JEV) causes a mosquitoborne viral zoonosis that is
      becoming increasingly important to public health in east and south Asia. Although
      JEV is primarily associated with reproductive failure in swine, JEV infection can
      cause fever and headache in humans and is associated with aseptic meningitis and
      encephalitis. The exact mode of transmission, including host range and possible
      source of viral amplification within livestock, is still not completely clear.
      This study consisted of a serological survey of JEV infection in goats. A total
      of 804 goat serum samples were collected from 144 farms in Korea between May 2005
      and May 2006. The incidence of positive cases was 12.1% (97 out of 804 goats).
      The seroprevalence of JEV infection in the 144 farms screened was 31.3% (45/144),
      indicating that JEV infection is frequent in goat farms in Korea. In addition,
      three districts of Korea (mainly in the southern region) had a higher
      seroprevalence of JEV compared to other areas. The results suggest that goats
      could be monitored epidemiologically as a sentinel animal for JEV transmission in
      Korea.

PMID- 17519577
TI  - Bilateral Polydactyly in a foal.
AB  - The following case report describes the diagnosis and surgery of bilateral
      polydactyly of unknown origin in a colt. A 7-month-old Berber colt was referred
      for cosmetic and curative excision of supernumerary digits. Radiographic
      examination revealed bilateral polydactyly and welldeveloped first carpal bones.
      Surgery consisted of an osteotomy of both second metacarpal bones combined with
      an amputation of the supernumerary digits. The follow-up at 18 months after
      surgery revealed a sound horse with an excellent cosmetic outcome.

PMID- 17519578
TI  - Retrieval of an embolization coil accidentally dislodged in the descending aorta
      of a dog with a patent ductus arteriosus.
AB  - A 3.5-year-old intact female miniature poodle (weighing 2.7 kg) was referred to
      the Veterinary Teaching Hospital at Kangwon National University, because of
      inadvertent aortic embolization, by an occlusion coil used for the closure of
      patent ductus arteriosus (PDA). The coil was found at the site of the branching
      renal arteries in the abdominal aorta. A foreign body forceps with a three-wire
      nail tip was used, with fluoroscopic guidance, to retrieve the coil. After the
      removal, the dog was treated with heparin to prevent thromboembolization.

PMID- 17519579
TI  - Analysis of perimenstrual asthma based on questionnaire surveys in Japan.
AB  - BACKGROUND: Perimenstrual asthma (PMA) has been documented in 30% to 40% of
      asthmatic women; the characteristics of PMA have also been well described.
      However, there have been few epidemiological investigations of PMA in practice.
      In this study, we analyzed PMA based on a questionnaire survey carried out in
      Japan and compared the results with those of studies reported previously.
      METHODS: For 8 weeks from September through October 2004, a questionnaire survey
      was administered to patients with bronchial asthma and their attending
      physicians. The questionnaire surveyed asthma control, asthma-related emergencies
      and satisfaction in daily life. The attending physicians were questioned about
      patient profiles and medications. All female patients who were menstruating
      during the survey period and who were known to have asthma exacerbation related
      to menstruation were allocated to the PMA group; those who were not were
      allocated to the non-PMA group. RESULTS: The rate of PMA in female patients who
      were menstruating during the survey period was 11.3% in this study.
      Characteristic features of the PMA group (n = 54) included more severe disease,
      worsened disease control and more aggressive patient management, including
      increased oral corticosteroid use compared with the non-PMA group. The rates of
      emergency episodes in the PMA group were higher than in the non-PMA group. There
      was a significant increase in aspirin intolerant asthma (AIA, 25.5%) in the PMA
      group compared with the non-PMA group (8.4%). CONCLUSIONS: Attention should be
      paid to the lack of knowledge regarding PMA in patients with asthma in actual
      clinical settings. The low rate of PMA reported in this study may be due to the
      study method using self-reports of PMA by patients without sufficient knowledge,
      and may not be an accurate representation of the actual incidence of the disease.
      The clinical similarity of PMA to AIA in this study may also provide a new
      insight into the mechanism of PMA.

PMID- 17519580
TI  - Late-onset anaphylaxis after ingestion of Bacillus Subtilis-fermented soybeans
      (Natto): clinical review of 7 patients.
AB  - BACKGROUND: Allergic reactions after ingestion of fermented soybeans have rarely
      been reported. Fermented soybeans were recently reported to be a causative food
      of IgE-mediated, late-onset anaphylaxis without early phase responses. The
      objectives of our study are to clarify the clinical and laboratory features and
      to characterize the allergens in allergy due to fermented soybeans. METHODS:
      Seven patients with suspected hypersensitivity to fermented soybeans, from whom
      informed consent had been obtained, underwent skin prick-prick tests with
      fermented soybeans and challenge test with fermented soybeans. Additionally,
      specific IgE against fermented soybeans and the allergens of fermented soybeans
      were detected by ELISA and IgE-immunoblotting, respectively. RESULTS: Seven male
      patients, aged 26 to 42 years (mean age, 33.1 years), participated. All patients
      reported generalized urticaria and dyspnea; 5, loss of consciousness; 2,
      collapse; 2, vomiting; and 2, diarrhea after fermented soybean ingestion. The
      interval between fermented soybean ingestion and onset of symptoms was 5 to 14
      hours (mean, 9.6 hours). All patients were positive on skin prick-prick tests
      with fermented soybeans. In 2 patients, oral challenge with fermented soybeans
      was positive 5.5 and 13 hours after ingestion. In ELISA, all 5 patients tested
      showed elevated IgE levels to the fermented soybean extract. Furthermore, IgE
      immunoblotting using 5 patients' sera showed six bands, of which three bands at
      38, 28, and 26-kd were bound to sera from 4 patients. CONCLUSIONS: Cases with
      hypersensitivity after ingestion of fermented soybeans most frequently correspond
      to IgE-mediated, late-onset anaphylactic reactions due to fermented soybeans.

PMID- 17519581
TI  - The new role of disodium cromoglycate in the treatment of adults with bronchial
      asthma.
AB  - BACKGROUND: Viral infection of the respiratory tract in patients with asthma is
      one of the most frequent causes of exacerbation of asthmatic symptoms. Disodium
      cromoglycate (DSCG) is a commonly used anti-asthmatic medicine with many
      beneficial biochemical and physiological effects. The purpose of this study was
      to investigate the efficacy of DSCG against colds when used in clinical practice.
      METHODS: A questionnaire survey to determine the efficacy of DSCG was undertaken
      in 220 adult patients with asthma (81 male, 139 female; mean age: 54.1 +/- 13.7
      years and 60.1 +/- 12.7 years, respectively) from April to September 2004 at the
      Miyatake Asthma Clinic. RESULTS: The duration of DSCG inhalation therapy was not
      less than 5 years in more than half of the patients. The mean daily DSCG dose at
      the time of the questionnaire survey was 40mg/day in over 50% of all patients.
      After DSCG was added to inhaled corticosteroid (ICS) combination therapy, 56.4%
      of the patients rated their condition as "improved", and 66.4% of the patients
      felt that the frequency of colds they had caught had decreased while DSCG was
      added to ICS. CONCLUSIONS: DSCG inhalation therapy is a useful additional
      treatment following ICS to alleviate asthma symptoms, and to prevent colds in
      adult patients with asthma.

PMID- 17519583
TI  - A case of angioedema associated with decreased C1 inhibitor activity.
AB  - BACKGROUND: We report a case of a 31-year-old woman who began to notice swelling
      of her arms at age 20. She was once given a diagnosis of cellulitis, but her
      symptoms spontaneously resolved. The patient had swelling of the left forearm and
      palm and was referred to our department for evaluation. She had slight pain but
      no obvious weight gain. CASE SUMMARY: Antinuclear antibody and other
      autoantibodies, including anti-ds-DNA antibody, anti-RNP antibody, anti-Sm
      antibody, and anti-SS-A antibody were not detected. C1 inhibitor activity was
      low, C3 was normal, C4 was low, CH(50) was low, and C1q was normal. DISCUSSION:
      Based on the presence of the typical clinical features and the positive results
      on the complement tests, we diagnosed hereditary angioedema. A decrease in C1
      inhibitor activity and an increase in specific protein concentrations indicated
      type 1.

PMID- 17519582
TI  - An evaluation of the clinical efficacy of tomato extract for perennial allergic
      rhinitis.
AB  - BACKGROUND: Recently, some common foods in daily life have been found to have
      anti-allergic effects. We have reported that tomato extract (TE) could possibly
      inhibit histamine release and mouse ear-swelling responses. Moreover, it is
      reported that TE could relieve the symptoms for Japanese cedar pollinosis.
      METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized,
      double-blind, placebo-controlled study in 33 patients with perennial allergic
      rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8
      weeks. RESULTS: We found that the sneezing score significantly decreased in the
      TE group at the end of the trial compared to the beginning (P < 0.05). There were
      decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The
      patients' quality of life was significantly improved in the TE group after 8
      weeks of treatment (P < 0.05), but not in placebo group. A significant
      improvement in total symptom scores, combining sneezing, rhinorrhea and nasal
      obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01).
      The safety of TE treatment was confirmed by laboratory tests and inspection of
      general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal
      symptoms of PAR.

PMID- 17519584
TI  - Drug-induced hypersensitivity syndrome associated with a marked increase in anti
      paramyxovirus antibody titers in a scleroderma patient.
AB  - BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is characterized by a
      severe multiorgan hypersensitivity reaction that usually appears after prolonged
      exposure to certain drugs and may be related to reactivation of herpes viruses.
      There have been few reports regarding the clinical association of DIHS with
      pathogens other than herpes viruses. CASE SUMMARY: We report a case of
      scleroderma with DIHS associated with paramyxovirus infection. A 61-year-old man
      with early diffuse cutaneous scleroderma with myositis and progressive
      interstitial pneumonia developed generalized erythema with high fever 3 weeks
      after taking sulfamethoxazole/trimethoprim. The diagnosis of DIHS was made based
      on the patient's history of using an offending drug, clinical manifestations and
      laboratory data showing peripheral eosinophilia with the presence of atypical
      lymphocytes. Virological tests showed significant increases of antibody titers
      against mumps virus and parainfluenza virus type 2, which strongly suggested that
      paramyxovirus infection occurred during the clinical course of DIHS. DISCUSSION:
      These findings suggest that paramyxovirus infection had contributed to the
      development of DIHS in this patient and that there is a need to seek evidence of
      other viral infections in some cases of DIHS, especially those without herpes
      virus reactivation/infection.

PMID- 17519585
TI  - No more terrifying experiences. Diabetes self-management requires knowledgeable,
      supportive nurses.

PMID- 17519586
TI  - Nurses, duty, and war. Supporting our troops, protecting our patients.

PMID- 17519587
TI  - Bad birthing.

PMID- 17519588
TI  - Full prescribing privileges.

PMID- 17519589
TI  - Violence and nursing.

PMID- 17519590
TI  - AJN in print.

PMID- 17519591
TI  - Electronic health records.

PMID- 17519596
TI  - Fighting for more than member benefits. Nursing unions embrace patient safety as
      part of their workplace mission.

PMID- 17519597
TI  - Extensively drug-resistant tuberculosis. Recent outbreaks highlight the need for
      improved prevention, control, and surveillance programs.

PMID- 17519604
TI  - Wound wise: wounds in surgical patients who are obese.
AB  - The number of surgical patients who are obese in the United States is rising, a
      trend that's likely to continue. Such patients are at higher risk than nonobese
      patients are for surgical site infections and other complications such as
      dehiscence, pressure ulcers, deep tissue injury, and rhabdomyolysis. This article
      details the factors that can contribute to such complications, including a high
      number of comorbidities, and offers practical suggestions for preventing them.
      Nurses should understand that special equipment, precautions, and protocols may
      be needed at every stage of care, and that obese patients aren't anomalies but
      rather a part of a growing population with particular needs.

PMID- 17519606
TI  - Emergency: heatstroke in older adults. In this population it's a short step from
      heat exhaustion.

PMID- 17519607
TI  - Healer's Heart.

PMID- 17519608
TI  - "Them" and "us": a view from the middle. An overreliance on regulations can
      demean both patients and staff.

PMID- 17519609
TI  - Hospital discharge of older adults. How nurses can ease the transition.
AB  - When an older adult is discharged from the hospital, she or he should have an
      individualized, comprehensive discharge plan to help prevent unnecessary
      complications and rehospitalization. But the large number of older adults who are
      hospitalized and their typically greater needs can make creating such a plan a
      challenge for clinicians. Clear communication among hospital personnel, patients,
      family members, case managers, and community caregivers (such as home health care
      nurses and long-term care staff) is essential. In examining effective discharge
      planning for this population, this article examines five discharge models.

PMID- 17519617
TI  - Nursing with the TQ Surgical in Iraq. The work of navy nurses at Camp Al
      Taqaddum.

PMID- 17519615
TI  - Executive summary: the state of the science on nursing best practices for
      diabetes self-management.

PMID- 17519618
TI  - Reflections: the vault. A dying friend's farewell ball.

PMID- 17519619
TI  - Primary cutaneous marginal zone B-cell lymphoma may exhibit both the
      t(14;18)(q32;q21) IGH/BCL2 and the t(14;18)(q32;q21) IGH/MALT1 translocation: an
      indicator for clonal transformation towards higher-grade B-cell lymphoma?
AB  - Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a recently proposed
      entity and constitutes the cutaneous counterpart of extranodal marginal zone B
      cell lymphoma of mucosa-associated lymphoid tissue (MALT). The t(14;18)(q32;q21)
      involving the IGH and the MALT1 gene has previously been described in PCMZL,
      whereas the t(14;18)(q32;q21) IGH/BCL2 seems to be restricted to follicular
      lymphoma and diffuse large B-cell lymphoma. We screened 30 PCMZLs of 13 patients
      by fluorescent in situ hybridization analysis for the presence of the
      t(14;18)(q32;q21) IGH/BCL2 and the t(14;18)(q32;q21)IGH/MALT1. The
      t(14;18)(q32;q21) IGH/MALT1 was detected in 10 PCMZLs of eight patients, with
      four patients showing the t(14;18)(q32;q21) IGH/MALT1 exclusively. The
      t(14;18)(q32;q21)IGH/BCL2 was detected in 16 PCMZLs of seven patients, with four
      patients showing the t(14;18)(q32;q21) IGH/BCL2 exclusively. Six lymphomas of
      four patients showed both translocations in the same lesion. In seven lymphomas,
      neither of the two translocations occurred. One patient developed multiple
      lesions without either of the two translocations. Our results underline that both
      the t(14;18)(q32;q21)IGH/BCL2 and the t(14;18)(q32;q21) IGH/MALT1 may occur in
      PCMZL, albeit in an irregular distribution. Therefore, the etiopathogenetic
      relevance of either translocation in PCMZL remains a matter of debate.

PMID- 17519620
TI  - Nature of inflammatory infiltrate in superficial cutaneous malignancies during
      topical imiquimod treatment.
AB  - Topical imiquimod (IQ) is an effective treatment for genital warts and various
      malignant tumors of the skin. IQ acts through the Toll-like receptor 7 leading to
      the production of cytokines and chemokines such as interferons, interleukins, and
      growth factors. We investigated the composition of the inflammatory cell
      infiltrate before, during, and after the treatment of 10 superficial cutaneous
      malignancies (melanoma in situ (n = 4), melanoma metastasis (n = 1), squamous
      cell carcinoma in situ (n = 4), and basal cell carcinoma (n = 1) with 5% IQ
      cream. Immunophenotyping revealed in all cases during treatment an increased
      population of T-lymphocytes positive for CD3, CD4 and CD8, as well as a
      considerable number of cytotoxic cells (TIA-1+, granzyme B+) and plasmacytoid
      dendritic cells (CD 123+). These findings further support previous investigations
      that the antitumor effects of IQ result from an enhanced cytotoxic T-cell
      mediated immune response and from the recruitment of plasmacytoid dendritic cells
      to the skin. The population of infiltrative inflammatory cells was similar in all
      patients irrespective of the type of tumor.

PMID- 17519621
TI  - Sebaceous carcinoma arising in nevus sebaceus of Jadassohn: a clinicopathological
      study of five cases.
AB  - The authors report a small series of sebaceous carcinoma developing in nevus
      sebaceus of Jadassohn (also known as organoid nevus) and analyze similar cases
      reported in the literature. All of our patients were females (age range 57-71
      years; median 60 years) who had the organoid nevus on the scalp, face, or nuchal
      area, the rest of which was recognized clinically and/or histologically. All
      sebaceous carcinomas manifested unquestionable architectural (asymmetry, invasive
      growth) and cytological features of a carcinoma (cellular and nuclear
      pleomorphism, plentiful atypical mitoses, necroses en masse), demonstrated
      unambiguous sebaceous differentiation in the form of mature sebocytes, and lacked
      other differentiations. The sebaceous carcinoma was always accompanied by other
      benign or malignant adnexal lesions such as sebaceoma, syringocystadenoma
      papilliferum, syringocystadenocarcinoma papilliferum, trichoblastoma,
      tricholemmoma, desmoplastic tricholemmoma, or syringoma. In three cases,
      prominent mucinous metaplasia of sweat ducts and glands was seen. In two of these
      cases, sweat ducts exhibited hyperplastic changes. The analysis of the previously
      published material and our cases indicates that sebaceous carcinoma arising in
      organoid nevus has a female predilection and tends to occur in elderly patients.
      It may involve any site where nevus sebaceus typically occurs. Clinically, the
      tumor presents as a solitary nodule, ulcerated tumor, or mass, often with a
      recent history of rapid growth. It may arise alone, but it occurs more frequently
      as part of multiple benign and malignant adnexal tumors. The lesion does not seem
      to be associated with Muir-Torre syndrome. The rest of organoid nevus is usually
      recognized both clinically and microscopically, although large tumors may
      overgrow and mask the nevus. The tumor seems to be a low-grade carcinoma in terms
      of clinical behavior.

PMID- 17519622
TI  - Merkel cell-poor trichoblastoma with basal cell carcinoma-like foci.
AB  - We reexamined 11 cases of trichoblastoma, and two cases of trichoblastoma with
      basal cell carcinoma (BCC)-like foci were found. In these two trichoblastomas
      with BCC-like foci, the BCC-like foci were often localized in peripheral or deep
      areas of lesions extending out of the fibrocytic stroma. Immunohistochemistry was
      performed in five conventional trichoblastomas and in two trichoblastomas with
      BCC-like foci, using antibodies against CK20 and CK15. No CK20-positive Merkel
      cells and no expression of CK15 were seen in any neoplastic aggregations of the
      two trichoblastomas with BCC-like foci. In contrast, increased numbers of Merkel
      cells and positive staining for CK15 were observed in all five trichoblastomas
      without BCC-like foci. The five trichoblastomas without BCC-like foci included
      two trichoblastomas with a popped out or shelled out appearance, which
      characteristically had a thick fibrous capsule surrounding the fibrotic stroma,
      demonstrating numerous Merkel cells in the aggregations. Some trichoblastomas may
      undergo mutations, resulting in the development of foci of BCC and in the loss of
      the expression of CK15 as well as the disappearance of Merkel cells.

PMID- 17519624
TI  - Incidental granular parakeratotic cornification in carcinomas.
AB  - Granular parakeratosis is histopathologically recognized by the presence of
      parakeratotic corneocytes housing keratohyaline granules. Similar to acantholytic
      dyskeratosis and epidermolytic hyperkeratosis, it may histopathologically
      represent a diagnostic finding in a specific dermatosis, one of the diagnostic
      features in a solitary keratosis or an incidental finding. Granular parakeratosis
      as an incidental finding has been reported in association with various
      dermatoses. This report expands the concept of granular parakeratosis as an
      incidental histopathologic feature by describing it in carcinomas. In addition,
      we also present the phenomenon of retained keratohyaline granules unaccompanied
      by a nucleus within corneocytes, ie, granular orthokeratotic cornification.

PMID- 17519623
TI  - Tubular adenoma and syringocystadenoma papilliferum: a reappraisal of their
      relationship. An interobserver study of a series, by a panel of
      dermatopathologists.
AB  - Tubular adenoma (TA) and syringocystadenoma papilliferum (SCAP) may show
      histopathological overlap, with some lesions having features of both neoplasms
      (SCAP + TA). TA has been recently suggested to represent a carcinoma. Four
      observers blindly assessed 67 cases of TA, SCAP, and their lookalikes (poroma,
      apocrine adenoma, apocrine carcinoma; all lesions focally featuring a
      pseudopapillary pattern), and classified the lesions into one of four categories:
      (1) TA, (2) SCAP, (3) SCAP + TA, and (4) others. Lesions were also classified as
      benign or malignant. In only 29 cases was there unanimous agreement among the
      four observers, who classified 22 lesions as TA, three as SCAP, and four cases as
      others. Of the 38 cases where there was interobserver diagnostic variation, in
      30, the diagnosis varied between TA or SCAP or SCAP + TA; the remainder fell in
      the others category. Analysis of the factors leading to interobserver variability
      indicated that diagnostic problems occurred when there were any of the following:
      epidermal acanthosis, papillomatosis, connection of the neoplastic tubules to the
      overlying epidermis and/or follicular infundibula, and plasma cell infiltration.
      These features accounted for the morphological overlap between TA and SCAP. All
      observers agreed that the lesions were benign; the only apocrine carcinoma
      included was recognized as such by all observers. From the study, it was
      concluded that TA may arise in the deep dermis without any epidermal connection,
      or, in other cases, it may be more superficially located with or without an
      epidermal connection. It may be reasonably inferred that, possibly as a response
      to infection, there may be accompanying plasma cells and variable acanthosis and
      papillomatosis, such that the appearances are those of "pure" SCAP, or lesions
      may have features "intermediate" or overlapping between TA and SCAP.

PMID- 17519625
TI  - Primary cutaneous metaplastic carcinoma: report of a case involving angiosarcoma.
AB  - Primary cutaneous metaplastic carcinoma is an uncommon cutaneous malignancy
      comprising a mixture of epithelial and mesenchymal components. The former is most
      frequently a squamous cell or basal cell carcinoma, and the latter is most
      typically a pleomorphic sarcoma or atypical fibroxanthoma. We describe the first
      primary cutaneous metaplastic carcinoma with angiosarcoma as the mesenchymal
      component arising on the scalp of a 90-year-old woman.

PMID- 17519626
TI  - Facial apocrine fibroadenoma in man: a rare finding.
AB  - Apocrine fibroadenoma (AFA), considered a counterpart of fibroadenoma of breast,
      is a rare cutaneous apocrine neoplasm occurring almost exclusively in women. We
      describe a 75-year-old man who presented with a red dome-shaped papule near the
      nasal bridge. The tumor was composed of numerous tubular, cystic, and partially
      branching lumina and struts of epithelial cells oriented perpendicular to the
      skin surface, with which it connected through infundibula. The epithelial strands
      were embedded in fibrocollagenous stroma. These histopathological features are
      consistent with AFA. The cytokeratin profiles of our case were similar to those
      of apocrine or eccrine neoplasms. Progesterone and estrogen receptors (PR/ER)
      were not expressed. The stroma cells were stained strongly positive for vimentin,
      but nonreactive for alpha-smooth muscle actin, S-100 protein, or glial fibrillary
      acidic protein. To the best of our knowledge, this is the first report of facial
      AFA in man. Different from a more common anogenital AFA, this neoplasm might
      represent a second type of AFA with unique histopathologic and immunopathological
      features.

PMID- 17519627
TI  - Oculocutaneous oncocytic tumors: clinicopathologic and immunohistochemical study
      of 2 cases with literature review.
AB  - Oculocutaneous oncocytic tumors (OCOTs) are uncommon neoplasms that have been
      reported only rarely in the dermatopathology literature and whose
      immunophenotypic profile has not been well characterized. The clinical,
      histologic, and immunophenotypic features of 2 cases seen by the authors were
      assessed, and relevant publications in the literature were reviewed. Both
      patients with OCOTs were adult women with gradually enlarging, asymptomatic
      lesions involving the caruncle; they were locally excised. Histologically, the
      tumors were well-circumscribed nodules comprised of large oxyphilic cells
      arranged in confluent sheets and forming glandular spaces with secretory
      material. Microcystic areas and sparse intermingled goblet-cells were also
      apparent. Nuclear atypia and infiltrative growth were absent. Mitotic activity
      was absent in one case; a single mitotic figure was identified in the other.
      Immunostains demonstrated uniform expression of pankeratin and mitochondrial
      antigens. Both neoplasms were also labeled for markers associated with cutaneous
      adnexal, lacrimal, and minor salivary glandular tissue, including alpha-1
      antitrypsin, gross cystic disease fluid protein-15, carcinoembryonic antigen,
      lysozyme and MUC1; each case expressed 4 of the 5 substances. Some cells
      expressed cytokeratins 5/6 and p63 consistent with the presence of basal-type
      differentiation in a subset of cells. No definite evidence of myoepithelial
      differentiation was demonstrated, as stains for smooth muscle actin, muscle
      specific actin, and S100 protein were negative. Estrogen and progesterone
      receptor proteins were absent; strong cytoplasmic immunoreactivity for androgen
      receptor protein was evident, but nuclear staining was absent. The authors
      conclude that OCOTs show glandular differentiation. A review of the literature
      disclosed that none of these lesions arising in the caruncle behaved
      aggressively, in contrast to occasional tumors in other oculocutaneous sites.

PMID- 17519628
TI  - Giant pilomatricoma.
AB  - A 52-year-old man was examined for an ulcerated, rapidly growing reddish nodule.
      It was 5.5 cm high with an 11 x 6-cm base and located on the left clavicle. The
      lesion had been present for approximately 7 years, and the patient complained
      occasional burning and pain. Clinical differential diagnoses included cutaneous
      lymphoma, sarcoma, squamous cell carcinoma, and cutaneous metastasis.
      Histopathologic examination revealed a well-circumscribed tumor involving the
      whole dermis and the subcutis and composed of partially confluent aggregates of
      matrical cells admixed with eosinophilic cornified material containing shadow
      cells. In addition, multinucleated giant cells, areas of calcification and
      metaplastic ossification, edema, and hemorrhage were also observed. On the basis
      of histopathologic features, the diagnosis of pilomatricoma was made. Our report
      highlights an unusual clinical appearance of pilomatricoma that made us consider
      a variety of primary or secondary cutaneous neoplasms in its differential
      diagnosis.

PMID- 17519629
TI  - Epidermotropic metastatic prostate carcinoma presenting as an umbilical nodule
      Sister Mary Joseph nodule.
AB  - Carcinoma of the prostate accounts for fewer than 1% of all skin metastases.
      Cutaneous metastases from prostate carcinoma most often involve the penis, the
      anterior aspect of the thighs, the suprapubic area, and the perineum, but they
      also have been reported in the scalp, the chest, the back, and even the face. We
      report an unusual case of metastatic prostate adenocarcinoma that presented as an
      umbilical nodule (Sister Mary Joseph nodule) and demonstrated significant
      epidermotropism histologically. A review of the literature has found only one
      documented case of prostatic carcinoma metastasizing to the umbilicus, and one
      other documented case of epidermotropic metastatic prostate carcinoma.

PMID- 17519630
TI  - The pseudo-Pelger-Huet anomaly in pyoderma gangrenosum associated with
      myelodysplastic syndrome.
AB  - We report a case of pyoderma gangrenosum in which most of the neutrophils
      exhibited the pseudo-Pelger-Huet (pPH) anomaly, a cytologic abnormality affecting
      the neutrophil nucleus. Pelgeroid cells have round, oval, or hyposegmented nuclei
      and are therefore difficult to recognize as neutrophils. The pPH anomaly is
      important because it is found mostly in patients with myelodysplastic syndromes
      or myeloid leukemias. These patients are also at risk for developing neutrophilic
      dermatosis as well as leukemia cutis, the main differential diagnosis. In our
      case, the proper diagnosis was made with the help of immunohistochemistry.

PMID- 17519631
TI  - Giant cell rich histiocytic dermatitis/panniculitis associated with
      thrombocytosis.
AB  - An unusual histiocytic dermatitis associated with a lymphoplasmacytic and
      histiocytic panniculitis appears to represent a previously undescribed disease
      process. A 56-year-old woman presented with a 5 year history of a violaceous,
      maculo-papular rash primarily on her legs. It began approximately 8 months before
      therapy for thrombocytosis. The rash subsequently progressed to form confluent
      patches and plaques on her torso and arms. The clinical impression was of
      disseminated granuloma annulare, but multiple biopsies from different sites did
      not confirm this. Histologic examination revealed a diffuse proliferation of
      histiocytic cells in the dermis, without well-formed granulomas or necrobiosis.
      The cells had large, focally irregular nuclei with prominent nucleoli, and were
      associated with scattered, often bizarre multinucleate giant cells.
      Immunohistochemistry demonstrated the histiocytic cells to be positive for S100
      and CD68 and negative for CD1a. Perivascular siderophages as well as a
      lymphoplasmacytic and histiocytic panniculitis accompanied the process. The
      striking cutaneous changes are of unknown etiology but appear to be previously
      undescribed.

PMID- 17519632
TI  - Histoplasma phimosis: an uncommon presentation of a not uncommon pathogen.
AB  - Infection from Histoplasma capsulatum is usually subclinical, but it also can be
      disseminated in patients with a compromised immune status. Involvement of the
      external genitalia is a rare finding, occurring by direct contact or hematogenous
      spread. We present a case of histoplasma posthitis in a 71-year-old man,
      manifesting with the extremely unusual presentation of phimosis. The diagnosis
      was confirmed using an immunohistochemical stain.

PMID- 17519633
TI  - Zosteriform connective tissue nevus: a case report.
AB  - Zosteriform connective tissue nevus is a rare form of connective tissue
      hamartomas, which arises from cells of mesodermal origin. Despite similar
      clinical appearance of many connective tissue nevi, they can be differentiated
      histochemically and/or biochemically on the basis of the primary connective
      tissue element present. There are only 3 reported cases of zosteriform connective
      tissue nevi in the worldwide literature. We report a case occurring in a 25-year
      old male with approximately 40 nodules and smaller papules distributed in a
      zosteriform fashion on the right lower lumbar region and upper gluteal region.
      The identification of the lesion by deep biopsy excluded the important
      differential diagnosis of segmental neurofibromatosis.

PMID- 17519634
TI  - Nonnecrobiotic necrobiotic xanthogranuloma.

PMID- 17519635
TI  - Squamous epithelial-lined cyst occurring in an aneurysmal fibrous histiocytoma.

PMID- 17519636
TI  - A surreptitious sinister sarcoma.
AB  - Angiosarcoma is an exceedingly rare endothelial-derived sarcoma that, when seen,
      usually presents as an expanding bruise-like patch or violaceous papule/nodule on
      the head of an elderly patient. Herein, we present the histologic features of an
      unusual case that defied initial diagnosis.

PMID- 17519638
TI  - Merkel cell carcinoma and Azzopardi phenomenon.

PMID- 17519639
TI  - Reply to Merkel cell carcinoma and Azzopardi phenomenon.

PMID- 17519640
TI  - A novel approach to rater training and certification in multinational trials.
AB  - Clinical trials are becoming increasingly international in scope. Global studies
      pose unique challenges in training and calibrating raters owing to language and
      cultural differences. Recent findings that poorly conducted interviews reduce
      study power, makes attention to raters' clinical skills critical. In this study,
      109 raters from 14 countries went through a two-step certification process on the
      Hamilton Depression and Anxiety Rating Scales: (i) an online didactic tutorial on
      scoring conventions, and (ii) applied clinical training, consisting of small
      language-specific groups in which raters took turns interviewing patients while
      observed by an expert trainer, and observation and evaluation of individual
      interviews. Translators were used when native-language trainers were unavailable.
      Those who were unable to attend the startup meeting received the training
      individually via telephone. Results found a significant improvement in raters'
      knowledge of scoring conventions, with the mean number of correct answers on the
      20-item test improving from 14.59 to 17.83, P<0.0001. In addition, raters'
      clinical skills improved significantly, with the mean score on the Rater Applied
      Performance Scale improving from their first to their second testing from 10.25
      to 11.31, P=0.003. These results support the efficacy of this applied training
      model in improving raters' applied clinical skills in multinational trials.

PMID- 17519641
TI  - Prolactin serum levels in paranoid versus nonparanoid male schizophrenia patients
      treated with risperidone.
AB  - The frequently seen side effect of hyperprolactinemia thought to be the 'price'
      paid for the antipsychotic treatment of schizophrenia. Various reports have
      linked the use of risperidone, an atypical antipsychotic drug, with the
      significant rise of prolactin levels. Thus, we set to assess possible difference
      between prolactin levels among schizophrenia subtypes in 45 male patients treated
      with stable doses (2-6 mg/day) of risperidone as antipsychotic monotherapy. All
      patients showed increased prolactin levels beyond the normal range, with a
      significant difference between the paranoid and all other groups (P<0.0001).
      Specifically, the paranoid patients' prolactin levels were higher than those of
      the schizoaffective and the disorganized ones. These results suggest that the
      blockade of higher dopamine activity in the paranoid schizophrenia corresponds to
      the prolactin increase, more than in the schizoaffective and disorganized
      subtypes. These findings are opposite of what was observed in the previous study
      of unmedicated patients.

PMID- 17519642
TI  - Olanzapine therapy in anorexia nervosa: psychobiological effects.
AB  - Dopamine impairments occur in anorexia nervosa. The aim of this study was to see
      whether treatment with the atypical dopamine antagonist antipsychotic olanzapine
      improves the disorder. Thirty anorexics, 18 restricted and 12 bingeing-purging,
      underwent a 3-month course of cognitive behavioral therapy, plus at random and
      double-blinded oral olanzapine (2.5 mg for 1 month, 5 mg for 2 months) in half
      and oral placebo in the other half of them. BMI, psychopathological aspects
      (eating disorder inventory, Hamilton Rating Scale, Buss-Durkee Rating Scale, Yale
      Brown Cornell for Eating Disorders Rating Scale, temperament-character
      inventory), and homovanillic acid blood concentrations for dopamine secretion,
      were monitored at baseline and then monthly during the trial. At the end of the
      trial BMI, total eating disorder inventory, total Yale Brown Cornell for Eating
      Disorders Rating Scale, Buss-Durkee Rating Scale, Hamilton Rating Scale scores
      and in olanzapine-treated patients the subitems of eating disorder inventory
      ineffectiveness and maturity fear, of Buss-Durkee Rating Scale direct
      aggressiveness, of temperament-characteristic inventory persistence had improved
      significantly. When stratified for anorexia nervosa subtype, BMI changes were
      significant among anorexia nervosa bingeing-purging patient, 'depression'
      (Hamilton Rating Scale) and 'direct aggressiveness' (Buss-Durkee Rating Scale)
      among anorexia nervosa bingeing-purging patients, 'persistence' (temprerament
      characteristic inventory), among anorexics restricted patients, with a trend
      toward significance for obsessivity-compulsivity (Yale Brown Cornell for Eating
      Disorders Rating Scale). homovanilic acid blood levels increased significantly in
      the cognitive behavioral therapy+olanzapine group. No correlations were observed
      between homovanilic acid concentrations and psychopathological parameters. The
      pharmacological treatment can significantly improve specific aspects of anorexia
      nervosa.

PMID- 17519643
TI  - Similar frequency of abnormal correlation between serum leptin levels and BMI
      before and after olanzapine treatment in schizophrenia.
AB  - Melkersson proposed leptin dysregulation as a factor in the olanzapine-induced
      metabolic dysfunction. Their suggestion was based on the absence of the expected
      positive correlation between serum leptin levels and the BMI, and the loss of the
      sex-dependent difference in leptin levels, which are higher in women. Although
      subsequent studies did not confirm that proposal, few of them assessed basal
      leptin levels and corrected for body fat percentage. Along with these variables,
      we added a precise definition of participants out of the expected positive
      correlation in a large sample of schizophrenia patients. Sixty patients (26 women
      and 34 men) with severe schizophrenia undergoing chronic hospitalization and
      conventional antipsychotic treatment were switched to olanzapine (10-20 mg/day).
      We assessed at baseline, and at weeks 8 and 16 of treatment, the percentage of
      participants with abnormal correlation (out of the 95% confidence interval in the
      regression line) between leptin levels and the BMI, and the correlation between
      leptin and insulin, glucose, the insulin resistance index, c-reactive protein
      (CRP) and treatment response. Leptin levels were higher in women than in men
      (P<0.01). The positive correlation between leptin levels, BMI and percentage of
      fat were preserved. After olanzapine, 3.8% of women and 2.9-5.8% of men were out
      the 95% confidence interval, and the proportion was similar at baseline. Glucose,
      insulin, the insulin resistance index and the CRP levels significantly increased
      after olanzapine. The impact of olanzapine on leptin regulation appears discrete
      and limited to a small number of participants. Additional studies must clarify
      the features that render them to metabolic dysregulation.

PMID- 17519644
TI  - A double blind, randomized, placebo-controlled trial of quetiapine as an add-on
      therapy to lithium or divalproex for the treatment of bipolar mania.
AB  - The aim of this study was to evaluate the efficacy and tolerability of quetiapine
      combined with lithium or divalproex in the treatment of bipolar mania. Patients
      were randomized to 6 weeks of quetiapine (up to 800 mg/day) and
      lithium/divalproex (Li/DVP) (target trough serum concentrations of 0.7-1.0 mEq/L
      and 50-100 microg/mL, respectively) or placebo and lithium/divalproex.
      Quetiapine+lithium/divalproex treatment (n=104) showed a 2.0-point greater
      improvement on the primary outcome (change from baseline in Young Mania Rating
      Scale total score at day 21) compared with placebo+lithium/divalproex (n=96), and
      a 2.8-point greater difference by day 42, but the differences between groups were
      not statistically significant. Other efficacy measures, however, did show a
      statistically significant advantage in favor of quetiapine+lithium/divalproex
      over lithium/divalproex monotherapy at day 42. Improvement of mean Young Mania
      Rating Scale scores with quetiapine+lithium/divalproex was numerically but not
      statistically significantly greater than lithium/divalproex monotherapy in the
      treatment of bipolar mania. Potential reasons for the failure of
      quetiapine+lithium/divalproex to differentiate from placebo+lithium/divalproex
      treatment on the primary outcome measure and the implications of this for the
      treatment of mania and future studies are discussed. Overall, the combination of
      quetiapine with lithium or divalproex was well tolerated.

PMID- 17519645
TI  - Factors associated with antipsychotic dosing in psychiatric inpatients: a
      prospective study.
AB  - The persistent use of doses in excess of recommended levels is associated with
      increased risks of adverse reactions without evidence of additional benefits.
      Such treatment modality was evaluated in hospitalized psychiatric patients.
      During a 6-year recruitment period, a consecutive series of psychiatric
      inpatients receiving antipsychotic therapy were included. At admission,
      sociodemographic and clinical data, including antipsychotic drug use, were
      collected, and the 18-item version of the Brief Psychiatric Rating Scale was
      administered. At discharge, data on antipsychotic drug therapy were collected.
      Prescribed daily doses were converted into multiples of the defined daily doses.
      Using a cut-off score of a prescribed daily dose/defined daily dose as a ratio of
      more than 1.5 both at admission and at discharge assessments, a total of 62
      (15.4%) patients persistently received high antipsychotic dose. With less
      stringent criteria (prescribed daily dose/defined daily dose as a ratio of more
      than 2), however, only 4.4% of the entire sample was persistently exposed to high
      antipsychotic doses. Bootstrapped linear regression analysis revealed that
      positive symptoms were positively associated with high antipsychotic dose,
      whereas negative symptoms were negatively associated with high antipsychotic
      dose. Antipsychotic polypharmacy at admission was the strongest predictor of
      persistently receiving antipsychotic doses in excess of recommended levels. This
      study showed that the use of high antipsychotic dosing is not an occasional
      event. Clinicians should consider that concurrent prescribing of two or more
      antipsychotic agents increases the probability of administering excessive dosing
      in the long-term.

PMID- 17519646
TI  - Relative antidepressant efficacy of bupropion and the selective serotonin
      reuptake inhibitors in major depressive disorder: gender-age interactions.
AB  - To determine whether age/gender-based differences in efficacy exist between
      bupropion and the selective serotonin reuptake inhibitors for major depressive
      disorder, we pooled the findings of 10 double-blind studies comparing bupropion
      with a selective serotonin reuptake inhibitor. Men (N=943) and women (N=1179)
      were divided into three age groups (younger than 40, 40-55, older than 55).
      Improvement in terms of the 17-item Hamilton Depression Rating Scale, as well as
      the Bech melancholia, anxiety-somatization, and insomnia factors of the Hamilton
      Depression Rating Scale was compared between the two treatment groups. Of 64 pair
      wise comparisons, only one was statistically significant. Specifically, more
      women treated with a selective serotonin reuptake inhibitor experienced a 50% or
      greater decrease in Hamilton Depression Rating Scale Anxiety-Somatization scores
      (58.8 versus 63.8%, P=0.0394). No difference, however, was seen in the degree of
      resolution of Hamilton Depression Rating Scale Anxiety-Somatization scores
      (continuous measure) between women treated with bupropion versus a selective
      serotonin reuptake inhibitor (P=0.114). Bupropion and the selective serotonin
      reuptake inhibitors, thus, appear to be equally effective in treating depressive
      symptoms, as well as anxious/somatic symptoms and insomnia in depression. No
      gender-related or age-related differences were found except that greater
      improvement was seen in anxious/somatic symptoms of depression among women during
      selective serotonin reuptake inhibitor treatment. This finding could, however,
      not be replicated when improvement in anxious/somatic symptoms was defined as a
      continuous measure.

PMID- 17519647
TI  - D-cycloserine does not enhance exposure-response prevention therapy in obsessive
      compulsive disorder.
AB  - Obsessive-compulsive disorder is a common, chronic, and oftentimes disabling
      disorder. The only established first-line treatments for obsessive-compulsive
      disorder are exposure and response prevention therapy and the serotonin reuptake
      inhibitors. Many patients do not experience complete symptom resolution with
      either modality and require augmentation approaches. Recent animal and clinical
      data suggest that D-cycloserine, a partial agonist that acts at the strychnine
      insensitive glycine-recognition site of the N-methyl-D-aspartate receptor
      complex, may enhance extinction learning that occurs in exposure-based
      psychotherapies. Given this, this study examined if D-cycloserine (250 mg)
      enhances the overall efficacy and rate of change of exposure and response
      prevention therapy for adult obsessive-compulsive disorder. Participants were 24
      adults meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria
      for obsessive-compulsive disorder. The study design was a randomized, double
      blinded, placebo-controlled augmentation trial examining exposure and response
      prevention therapy+D-cycloserine versus exposure and response prevention
      therapy+placebo. All patients received 12 weekly sessions of exposure and
      response prevention treatment. The first session involved building a ritual
      hierarchy and providing psychoeducation about obsessive-compulsive disorder. The
      second session involved a practice exposure. Sessions 3-12 involved exposure and
      response prevention exercises. D-cycloserine or placebo (250 mg) was taken 4 h
      before every session. No significant group differences were found across outcome
      variables. The rate of improvement did not differ between groups. The present
      results fail to support the use of D-cycloserine with exposure and response
      prevention therapy for adult obsessive-compulsive disorder. As this study is the
      first to explore this question and a number of methodological issues must be
      considered when interpreting the findings, the conclusions that may be drawn from
      our results are limited.

PMID- 17519648
TI  - Prevalence and nature of side effects during clozapine maintenance treatment and
      the relationship with clozapine dose and plasma concentration.
AB  - Clozapine is associated with non-neurological side effects that can be
      subjectively unpleasant and/or clinically serious. We sought to: (i) assess the
      nature and prevalence of side effects experienced by patients receiving
      maintenance treatment with clozapine and (ii) explore the relationship between
      clozapine plasma concentration and side effect burden. Patients were receiving
      clozapine maintenance treatment. Open questioning followed by systematic enquiry
      using the Antipsychotic Non-neurological Side Effects Rating Scale were used to
      assess side effects. Trough plasma clozapine and norclozapine concentrations were
      measured. One hundred and three patients participated. On open questioning, 61
      patients reported a total of 117 side effects, whereas systematic enquiry
      identified an additional 649 side effects, with each patient reporting at least
      one. Clozapine plasma concentrations were significantly but weakly correlated
      with total Antipsychotic Non-neurological Side Effects Rating Scale score
      (Pearson correlation=0.29, P<0.004). Patients with a plasma clozapine
      concentration >0.25 mg/l were significantly more likely to have moderate/severe
      side effects than patients with lower plasma concentrations (63/76 vs. 12/23,
      chi=9.07, d.f.=1, P<0.01). The side-effect burden associated with maintenance
      clozapine treatment is high and the true extent can only be ascertained by
      systematic inquiry. The use of target plasma concentrations below those used for
      acute treatment should be explored as a strategy for minimizing side effects.

PMID- 17519649
TI  - Dose-dependent constipation with higher doses of quetiapine: a case series.
AB  - Quetiapine is a dopamine D2 and serotonin 5-HT2 antagonist with antipsychotic and
      mood-stabilizing properties. Recent studies suggest that higher doses of
      quetiapine combine superior therapeutic efficacy with good tolerability. We
      present five patients, in whom treatment with higher doses of quetiapine was
      associated with constipation. Our observations raise the question of dose
      dependent constipation under treatment with quetiapine.

PMID- 17519650
TI  - Concomitant use of lamotrigine and aripiprazole increases risk of Stevens-Johnson
      syndrome?
AB  - Stevens-Johnson syndrome is a severe and potentially life-threatening cutaneous
      reaction associated with lamotrigine. The incidence of developing Stevens-Johnson
      syndrome during lamotrigine therapy is low. On the basis of the glutamate and
      dopamine neuron dysregulation hypothesis in schizophrenia, we propose new
      strategies for the treatment of schizophrenic patients using a glutamate system
      stabilizer lamotrigine as an adjunctive treatment for the poor responders of a
      dopamine system stabilizer, aripiprazole. The finding of Stevens-Johnson syndrome
      in two cases out of three treated with lamotrigine plus aripiprazole, however,
      has a much higher index of suspicion and it is correct to warn of its possible
      raised risk. As lamotrigine is currently licensed for the prophylactic treatment
      of bipolar depression, many of these patients have psychotic features where it
      would be considered reasonable to add an antimanic atypical antipsychotic such as
      aripriprazole. The two case reports raised the question about the possible
      increased risk of Stevens-Johnson syndrome with the combination therapy.

PMID- 17519651
TI  - Assessing patients with epiphora who are patent to syringing: clinical predictors
      of response to dacryocystorhinostomy.
AB  - PURPOSE: To assess the value of an abnormal fluorescein dye disappearance test
      (FDDT), lacrimal syringing, and Jones test for patients with epiphora who are
      clinically patent to syringing. METHODS: Prospective cohort study of 68
      consecutive patients with epiphora who were clinically patent to syringing and
      otherwise normal to examination. Patients were assessed using FDDT and lacrimal
      syringing, as well as the Jones test comparing either single- or multiple-drop
      technique. FDDT and canalicular reflux on lacrimal syringing were subjectively
      graded. RESULTS: Success was defined as nil or only mild epiphora after surgery.
      Surgery was performed on 68 patients with a successful result in 64 (94%). The
      majority of these patients had severely delayed FDDT (90%), > or = 50% reflux on
      lacrimal syringing (78%), or were Jones I negative (81%). There was no
      significant difference between outcomes of the single- and multiple-drop tests.
      In patients examined with the single-drop Jones test, patients with a Jones I
      negative result had a statistically significant better surgical outcome (p =
      0.04). This comparison was highly significant when the subgroup of patients with
      severely delayed/nonclearing FDDT and > or = 50% reflux was examined (p = 0.005).
      The results were not significant for the multiple-drop group. CONCLUSIONS: These
      findings show that a negative single-drop Jones I test is predictive of
      symptomatic improvement after dacryocystorhinostomy surgery in patients with
      epiphora who are clinically patent to syringing. Lacrimal syringing and the FDDT,
      on their own, were not predictive of surgical outcome. Jones testing was of
      significant value in patients, but only when the traditional single-drop test was
      used.

PMID- 17519652
TI  - Transcanalicular dacryocystorhinostomy with diode laser: long-term results.
AB  - PURPOSE: To evaluate the effectiveness of transcanalicular dacryocystorhinostomy
      with diode laser in treatment of epiphora in adults. METHODS: A prospective,
      noncomparative, interventional case series of transcanalicular
      dacryocystorhinostomy in 25 patients presenting with epiphora due to nasolacrimal
      obstruction. Patient age ranged from 32 to 72 years. Patients were evaluated
      postoperatively at 12, 24, and 36 months. Patients were evaluated for symptom
      improvement through a visual analog scale, and patency of osteotomy by lacrimal
      system irrigation with fluorescein and direct visualization by nasal endoscopy.
      Success was defined as resolution of epiphora. RESULTS: Transcanalicular
      dacryocystorhinostomy was able to re-establish patency of the lacrimal system in
      88% of cases after 36 months of surgery. No differences were found between
      patients older than 65 years and younger patients (chi-square, p > 0.05). Early
      (12 months) and late (36 months) results were similar (chi-square, p > 0.05).
      CONCLUSIONS: In this prospective series, transcanalicular dacryocystorhinostomy
      was effective in treatment of epiphora in adults with little morbidity.

PMID- 17519653
TI  - Effect of timing of external dacryocystorhinostomy on surgical outcome.
AB  - PURPOSE: To present our experience with external dacryocystorhinostomy (DCR)
      outcome and to compare cases of early and late DCR. METHODS: Retrospective data
      review of all patients who had external DCR with silicone intubation in a 7-year
      period. Data were collected and analyzed concerning patients' preoperative and
      postoperative symptoms, and the lacrimal drainage system examination before,
      during, and after surgery. RESULTS: In all, 162 patients underwent 195 DCR
      surgeries for nasolacrimal duct obstruction. Success was achieved in 81% of
      surgeries. Success rates were higher in patients who had early DCR (tearing only
      or early inflammatory signs of the lacrimal sac, 84% success) than in cases that
      had late DCR (more than 6 months after inflammation started, 77% success). These
      differences were statistically insignificant. Failure of DCR was much higher in
      posttraumatic DCR than in DCR for other etiologies. Complications (in 9% of
      surgeries) were generally mild and infrequent, except 1 case of meningitis.
      CONCLUSIONS: In experienced hands, external DCR has good postoperative success
      with a low complication rate. Early DCR does not have a substantial advantage
      over late surgery with regard to surgical outcome.

PMID- 17519654
TI  - Papillary thyroid carcinoma with thyroid-associated orbitopathy in a euthyroid
      state.
AB  - PURPOSE: Thyroid cancers with concurrent thyroid-associated orbitopathy (TAO) are
      extremely rare. The present study reports 5 unusual cases of papillary thyroid
      microcarcinoma in patients presenting with TAO in an euthyroid state. METHODS: We
      retrospectively reviewed the records of 5 patients (4 female, 1 male) with no
      known history of thyroid disease, who initially presented with TAO and were
      subsequently found to have thyroid cancer. TAO was diagnosed by a combination of
      computed tomography and clinical symptoms and signs. All patients underwent
      routine serologic assessment of thyroid hormones and thyroid-related
      autoantibodies including thyrotropin-receptor antibodies, as well as imaging
      studies such as neck ultrasonography or thyroid scintiscan with I. RESULTS:
      Patients presented with asymmetric proptosis (cases 1-3), ocular motility
      restriction (cases 1-3), and eyelid retraction (cases 1-5). None of the patients
      showed clinical signs of hyperthyroidism, and all returned normal thyroid
      function test data. Thyroid nodules were detected by neck imaging; subsequent
      fine-needle aspiration biopsies were performed with the cytologic result of
      papillary carcinoma. In no cases did ophthalmic symptoms resolve following cancer
      treatment (e.g., thyroidectomy and radioactive iodine therapy). All patients were
      positive for thyroid-binding inhibiting immunoglobulin in low titers.
      CONCLUSIONS: Although coincident occurrence is rare, patients presenting with TAO
      should be carefully evaluated for the possible presence of papillary
      microcarcinoma, which can develop in a setting of systemic autoimmunity without
      inducing hyperthyroidism.

PMID- 17519655
TI  - Beveled osteotomy with lateral wall advancement and interpositional bone grafting
      for severe thyroid orbitopathy.
AB  - PURPOSE: To present a new technique for orbital decompressions for patients with
      severe thyroid orbitopathy that minimizes complications while maximizing the
      amount of decompression. This method involves advancing the lateral orbital wall
      in such a way as to promote osseous union and minimize cosmetic deformities.
      METHODS: This paper represents a case series (42 eyes from 26 patients) of
      orbital decompressions for severe thyroid related orbitopathy. All patients were
      treated via a graded balanced orbital decompression with advancement of the
      lateral orbital wall with interpositional bone grafts. Preoperative and
      postoperative measurements were tabulated and statistically analyzed. RESULTS:
      All patients demonstrated significant improvement in proptosis with an average
      Hertel exophthalmometry reduction of 8 mm. In addition, 22 patient orbits with
      preoperative elevation of intraocular pressure demonstrated an average 7 mm Hg
      improvement in postoperative intraocular pressure. Seven patients required
      strabismus surgery postoperatively and no patient developed new onset strabismus
      after surgery. Of all patients, 54% demonstrated improvement of visual acuity of
      greater than 1 line and no patient experienced a decrease in visual acuity.
      Postoperative computed tomography scan demonstrated osseous union of the lateral
      wall after advancement with this new technique. No patient complained of a
      palpable deformity of the lateral orbital wall. CONCLUSIONS: The graded balanced
      orbital decompression with interpositional bone grafts effectively decompressed
      the orbit with significant improvement in final visual acuity, exophthalmometry
      measurements, and final intraocular pressure. In addition, this technique
      promotes osseous union with minimal cosmetic deformities.

PMID- 17519656
TI  - Errors of single-mirror or prism Hertel exophthalmometers and recommendations for
      minimizing the errors.
AB  - PURPOSE: Analysis is performed of the geometry of a Hertel exophthalmometer to
      determine the intrinsic error of reading that results from using the instrument
      in the manner that the manufacturer intended. Recommendations for improvement of
      the design and/or use of the instrument are made based on the findings. METHODS:
      A schematic drawing of the manufacturer-recommended use of an exophthalmometer is
      created. The geometry is analyzed to reveal the sources of error in the
      exophthalmometer reading and an equation for the magnitude of the error is
      derived. RESULTS: The exophthalmometer reading error is directly proportional to
      the difference between the reading obtained and the reading at the no-parallax
      alignment position used to make the reading (commonly 18 mm), with the reading
      being low when the reading is greater than the no-parallax-alignment position and
      high when the reading is less. The error is increased by the observer's eye being
      closer to the reflecting surface and by widening the base or separation of the 2
      reflecting surfaces of the instrument. The exophthalmometer reading may be 1.7 mm
      less than actual when it reads as 35 mm, which is 17 mm from the no-parallax
      alignment position. CONCLUSIONS: To minimize error in exophthalmometer readings,
      the reading should be as close to the no-parallax-alignment-position as possible.
      Exophthalmometers should therefore be modified to have multiple sets of no
      parallax-alignment lines, each pair of a different color. The instrument should
      be used with the narrowest feasible base and the examiner should be consistently
      positioned as far from the reflecting surface of the instrument as possible.

PMID- 17519657
TI  - Orbital lipoma: 2 cases and review of literature.
AB  - PURPOSE: Lipomas are rare benign tumors of the orbit that can resemble a variety
      of other orbital masses. We present 2 patients with orbital lipomas and review
      the literature. METHOD: Retrospective review of clinical charts, imaging studies,
      and pathology specimens. RESULTS: We encountered 2 patients with lipomas, both
      presenting with orbital swelling and a mass noted on clinical examination. A well
      circumscribed lesion was seen on CT, which on excision was composed of mature fat
      cells arranged in lobules and surrounded by a diaphanous capsule. CONCLUSIONS:
      Lipomas arising in the orbit may evoke a range of clinicoradiologic differential
      diagnoses.

PMID- 17519658
TI  - Complications of pegged and non-pegged hydroxyapatite orbital implants.
AB  - PURPOSE: The purpose of this study is twofold: to assess the incidence and
      implications of complications unique to placing a freestanding polycarbonate peg
      in patients with hydroxyapatite implants and to compare the incidence of
      complications in these patients with the incidence in patients with non-pegged
      hydroxyapatite implants. METHODS: This is a retrospective clinical case series of
      103 patients who underwent hydroxyapatite implant insertion at our institution.
      The incidence of postoperative complications in patients who underwent
      freestanding polycarbonate pegging procedures (n = 21) and those who had not (n =
      82) were compared. RESULTS: One postoperative complication - infection - occurred
      in a significantly higher percentage of patients in the pegged group (42.9%,
      9/21) compared with the non-pegged group (19.5%, 16/82), (p = 0.037). Fifteen of
      the 21 patients (71.4%) in the pegged group experienced complications unique to
      freestanding polycarbonate pegging. Overall, 95.2% (20/21) of patients in the
      pegged group experienced a complication compared with 58.5% (48/82) of patients
      in the non-pegged group, (p = 0.001). In addition, there was an average of 3.1
      (66/21) complications per patient in the pegged group compared with an average of
      1.9 (106/82) complications per patient in the non-pegged group (p = 0.010).
      CONCLUSIONS: Patients who received a freestanding polycarbonate pegged implant
      had a high risk of experiencing complications unique to pegging, and therefore a
      significantly higher rate of complications overall when compared with patients
      whose implant was not pegged. In addition, patients who received a pegged implant
      had a higher incidence of infection. However, most patients retained their pegs
      despite complications.

PMID- 17519659
TI  - Eyelid mucous membrane grafts: a histologic study of hard palate, nasal
      turbinate, and buccal mucosal grafts.
AB  - PURPOSE: To histologically evaluate the outcome of mucous membrane grafts to the
      eyelid. METHODS: Case series of 31 eyes from 24 patients who underwent
      transplantation of hard palate (25 eyes), buccal (1 eye), or nasal turbinate (5
      eyes) mucosa to the posterior eyelid surface. These grafts were biopsied at 0.5
      months to 84 months (mean, 20 months) postoperatively. They were examined with
      light microscopy and compared with either the donor mucosa from the same patient
      (2 patients) or the typical donor site histology (22 patients). RESULTS: Graft
      biopsies revealed general epithelial morphology that was quite similar to the
      respective donor sites in virtually all cases. Six (25%) of 24 hard palate graft
      biopsies, which were obtained at 8 months to 49 months (mean, 22 months)
      postoperatively, displayed orthokeratosis alternating with parakeratosis, while
      12 (50%) demonstrated parakeratosis alone, and another 6 (25%) showed adjacent
      regions of parakeratotic and nonkeratinized epithelium. No hard palate grafts
      showed complete absence of keratinization after transplantation. Other
      significant findings included loss of goblet cells in nasal turbinate grafts and
      few submucosal glands remaining in any specimen. CONCLUSIONS: Full-thickness
      mucosal grafts typically maintain their native epithelial morphology following
      transplantation to the ocular surface. Submucosal glands usually do not survive
      transplantation, which could be the result of intentional thinning of the graft
      at the time of transplantation. Contrary to the opinion that hard palate graft
      epithelium usually undergoes metaplasia from keratinized to nonkeratinized within
      6 months following transplantation to the eye, all hard palate grafts in this
      study remained orthokeratotic and/or parakeratotic.

PMID- 17519660
TI  - A randomized clinical trial of two methods of fascia lata suspension in
      congenital ptosis.
AB  - PURPOSE: To compare the results of 2 methods of upper eyelid sling placement with
      autogenous fascia lata in the treatment of congenital ptosis. METHODS: In a
      randomized clinical trial, patients with congenital upper eyelid ptosis and poor
      levator function (<4 mm) were randomly assigned to either of 2 methods of upper
      eyelid sling placement: group A, bitriangular fascia sling (modified Crawford
      method), and group B, monotriangular fascia sling (modified Fox method). RESULTS:
      This study included 30 upper eyelids (15 eyelids in each surgical group) of 19
      patients (8 unilateral and 11 bilateral cases) with congenital ptosis. Mean
      increase in eyelid fissure height was 2.7 +/- 2.3 mm in group A and 3.4 +/- 2.2
      mm in group B. Change in eyelid fissure in both groups was significant (p <
      0.001, paired t test) but the intergroup difference was not (p = 0.4, independent
      sample t test). Early complications such as corneal epithelial defects and
      entropion and late complications such as undercorrection were comparable in the 2
      groups. No patient experienced recurrent ptosis requiring reoperation in either
      group. CONCLUSIONS: The monotriangular method of upper eyelid fascia sling
      placement can be used instead of the more popular bitriangular method. Advantages
      include less need for fascial tissue, less periocular scar formation, and a
      shorter period of anesthesia.

PMID- 17519661
TI  - Comparison of the outcomes of internal-fixation versus bolster-suture
      tarsorrhaphy.
AB  - PURPOSE: To compare the outcomes of 2 techniques of permanent tarsorrhaphy.
      METHODS: The clinical records of 30 patients who underwent tarsorrhaphy at a
      single university-based hospital clinic were reviewed. Patients underwent
      permanent tarsorrhaphy because they had a nonresolving facial palsy, neurotrophic
      keratopathy unresponsive to medical treatment, or both. Permanent tarsorrhaphies
      were carried out by either internal fixation tarsorrhaphy or rubber bolster
      suture tarsorrhaphy. RESULTS: The overall success (100%) of internal fixation
      tarsorrhaphy on 12 patients (ages, 42.0 +/- 17.6 years) was significantly better
      than that of rubber bolster suture tarsorrhaphy (44.4%) on 18 patients (ages,
      40.6 +/- 25.5 years) (Mann-Whitney U test, p = 0.01). Of the 10 patients who had
      unsuccessful outcomes, 8 (80%) had their eyelids separated within the first 3
      postoperative weeks. Patients whose surgical outcomes were deemed successful were
      followed for a period of 21.4 +/- 10.7 weeks (range, 11-52 weeks). CONCLUSIONS:
      Internal fixation tarsorrhaphy is associated with a more favorable outcome than
      rubber bolster suture tarsorrhaphy in patients who require permanent eyelid
      closure.

PMID- 17519662
TI  - Rapamycin for treatment of refractory dysthyroid compressive optic neuropathy.
AB  - We report a patient with dysthyroid optic neuropathy refractory to steroids and
      orbital decompression treated with rapamycin, a fibroblast and T cell inhibitor.
      Symptoms, visual acuity, color plate testing, and visual fields improved. Aside
      from hypercholesterolemia, no complication related to this therapy was observed.
      By addressing the pathogenesis of thyroid eye disease, rapamycin may represent an
      alternative when standard treatments fail. Further investigation of rapamycin for
      treatment of dysthyroid orbitopathy is warranted.

PMID- 17519663
TI  - A novel approach to the management of severe facial disfigurement in
      neurofibromatosis type 1.
AB  - A 12-year-old girl with neurofibromatosis type 1 underwent subtotal anterior
      exenteration of a blind, unsightly, buphthalmic eye and orbital/eyelid plexiform
      neurofibroma. Simultaneously, a channeled Medpor orbital implant was positioned
      to reduce a meningoencephalocele resulting from severe sphenoid wing dysgenesis.
      Two-stage osseointegration was subsequently performed to permit secure fitting of
      an orbital prosthesis. This patient's cosmesis and social interaction were
      improved markedly with this surgical approach for disfiguring ocular, eyelid, and
      orbital disease due to neurofibromatosis type 1.

PMID- 17519664
TI  - Free tarsal graft combined with skin transposition flap for full-thickness lower
      eyelid reconstruction.
AB  - We present the surgical outcome in a series of 4 patients with large full
      thickness eyelid defects after basal cell carcinoma excision. The patients
      underwent reconstructive eyelid surgery using autogenous free tarsal grafts
      combined with a skin transposition flap from the upper eyelid. Two female and 2
      male patients ranging in age from 44 years to 85 years were treated. In all 4
      cases, posterior lamellae were reconstructed using a free tarsal graft, and the
      outer lamella was developed with a transposition skin flap from the upper eyelid.
      The skin flap provided adequate vascular support in all cases. Follow up of 10
      months to 20 months showed a good outcome in all patients. Reconstruction of full
      thickness eyelid defects after extensive tumor excision requires reforming of the
      anterior and posterior lamella. Whereas the Hughes or Cutler Beard techniques for
      eyelid reconstruction require a 2-step approach with occlusion of the eye for at
      least 1 week, reconstruction with a free tarsal graft is a 1-stage procedure and
      does not entail eye occlusion. Autogenous tarsus as a free graft proves to be a
      simple procedure for posterior lamella substitution in lower eyelid surgery,
      especially in combination with a skin transposition flap from the upper eyelid.

PMID- 17519665
TI  - Simple alternative to the Wright needle in frontalis sling surgery.
AB  - The Wright needle is a widely used instrument for insertion of fascia lata or a
      synthetic material during frontalis suspension surgery; however, difficulties in
      handling this instrument are frequently encountered by many surgeons. We describe
      an 18-gauge needle with a 4/0 monofilament polypropylene suture as an alternative
      to the Wright needle for placement of the sling material in frontalis suspension
      surgery. Less slippage and easier control of the needle's direction and depth of
      tissue penetration result in more accurate placement of the material and a
      reduction in damage to the surrounding tissues.

PMID- 17519666
TI  - Resection of an orbital rim intraosseous cavernous hemangioma and reconstruction
      by chin graft and resorbable fixation plate.
AB  - Intraosseous hemangiomas are uncommon in the orbital rim and pose difficulties
      for removal and reconstruction. Here we report an excellent cosmetic and
      functional outcome following en bloc resection and reconstruction, using a
      corticocancellous bone graft from the chin and LactoSorb perforated tray plate.
      The lesion treated is characterized by both computed axial tomography and
      histology, while the postsurgical bony contour also is revealed by CT.

PMID- 17519667
TI  - Lacrimal gland pleomorphic adenomas with low-density zones resembling cystic
      change on computed tomography.
AB  - We report 2 cases of pleomorphic adenoma with unusual radiologic findings. CT
      showed lacrimal gland masses dominated by low-density areas resembling cysts.
      Pathology revealed the lesions to be pleomorphic adenomas with myxomatous and/or
      cartilaginous features.

PMID- 17519669
TI  - Retrobulbar orbital abscess secondary to dacryocystitis in a neonate.
AB  - A retrobulbar orbital abscess secondary to congenital dacryocystitis is extremely
      rare. External abscess drainage, probing, and syringing with broad spectrum
      intravenous antibiotics was performed in a 22-day-old neonate who was examined
      for congenital dacryocystitis complicated by retrobulbar orbital abscess
      formation.

PMID- 17519668
TI  - Benign fibrous histiocytoma associated with a frontoethmoidal mucopyocele and
      orbital abscess.
AB  - A 74-year-old man sought treatment for painful swelling in the right upper
      eyelid. CT demonstrated a frontoethmoidal mucocele extending in the right orbit
      with abscess formation. Following functional endoscopic sinus surgery, the
      inflammatory symptoms in the right eye nearly resolved. However, a firm mass was
      still noted in the same location. Histopathologic examination proved it to be a
      benign fibrous histiocytoma. Benign fibrous histiocytoma may occur in association
      with an orbital abscess secondary to mucocele.

PMID- 17519670
TI  - Nasolacrimal duct obstruction with Urbach-Wiethe syndrome.
AB  - An 80-year-old woman presented with signs and symptoms consistent with bilateral
      nasolacrimal duct obstruction. She also was noted to have multiple eyelid margin
      lesions. She underwent bilateral dacryocystorhinostomy with biopsy of the
      nasolacrimal ducts and eyelid lesions. Her tearing resolved. Histopathology of
      the eyelid lesions was consistent with lipoid proteinosis. Nasolacrimal duct
      obstruction may occur in patients with lipoid proteinosis (Urbach-Wiethe
      syndrome).

PMID- 17519671
TI  - Reactive lymphoid hyperplasia of the nasolacrimal duct presenting as bloody
      epiphora.
AB  - A 90-year-old man reported a 1-year history of tearing and irritation in the left
      eye. Ophthalmic examination was significant for bloody mucopurulent material
      expressed from the left nasolacrimal duct. The patient underwent external
      dacryocystorhinostomy with excision of a soft-tissue mass. Initial
      histopathologic examination of the specimen revealed an atypical lymphoid
      infiltrate. Subsequent immunohistochemistry suggested that the mass was reactive
      lymphoid hyperplasia. Lymphoid hyperplasia should be considered in the
      differential diagnosis of bloody epiphora, in addition to primary malignancy of
      the nasolacrimal duct, hematologic abnormalities, coagulopathies, vascular
      tumors, and giant papillary conjunctivitis.

PMID- 17519672
TI  - Ophthalmologic presentation of nasal chondromesenchymal hamartoma in an infant.
AB  - A 7-month-old infant was examined for severe right ptosis, strabismus, and noisy
      breathing. CT revealed a right intranasal mass with areas of calcification,
      erosion, and extension to the cribriform plate. Surgical resection was performed.
      Pathologic examination confirmed the diagnosis of nasal chondromesenchymal
      hamartoma. Ophthalmologists may be among the first medical practitioners to
      encounter nasal chondromesenchymal hamartoma, a rare, benign neoplasm of the
      nasal and paranasal sinuses.

PMID- 17519673
TI  - Ectopic brain in the orbit with congenital adduction deficit and simultaneous
      abduction.
AB  - An 11-month-old girl was referred to us with enophthalmos and restriction of
      ocular movement in the right eye. There was restriction of supraduction and
      adduction with synergistic divergence on left gaze. MRI revealed a multiloculated
      cystic mass in the right inferior orbit. There was an atrophic and misinserted
      inferior rectus muscle and only a vestigial right medial rectus muscle.
      Excisional biopsy of the orbital cystic mass was performed. Microscopic
      examination disclosed that the mass was brain tissue composed of arachnoid
      tissue, brain parenchyma, choroid plexus, and dura mater. Our report describes a
      rare case of ectopic brain in the orbit that was combined with anomalies of the
      extraocular muscles.

PMID- 17519674
TI  - Orbital chordoid meningioma: a rare subtype of meningioma.
AB  - A 34-year-old woman presented with progressive proptosis of the right eye for 2
      years. MRI revealed a well-demarcated mass in the right intraconal space, which
      was isointense on T(1)- and hyperintense on T(2)-weighted images with bright
      uniform enhancement. The mass was resected through a lateral orbitotomy.
      Histopathologic examination revealed cords and clusters of spindle and
      epithelioid cells embedded in a myxoid matrix, with vacuolated eosinophilic
      cytoplasm and round nuclei. The tumor cells were diffusely positive for
      epithelial membrane antigen and vimentin. These findings helped confirm the
      diagnosis of chordoid meningioma, a rare variant of meningioma with a greater
      risk of recurrence and aggressive growth. Many of the clinical manifestations and
      imaging findings were indistinguishable from those of cavernous hemangiomas,
      solitary fibrous tumors, neurofibromas, and other variants of meningiomas. Given
      the prognostic significance of chordoid meningioma, extra care and attention
      should be given during surgery, histopathologic assessment, and follow-up.

PMID- 17519675
TI  - Epibulbar conjunctival fibroma.
AB  - A nodular, epibulbar mass appearing in an adult woman without antecedent
      inflammation or injury prompted concern for possible malignancy. Excision was
      performed, and pathologic examination demonstrated a conjunctival fibroma. The
      rarity of the fibroma and its clinical similarity to other benign or malignant
      tumors render its clinical diagnosis elusive.

PMID- 17519676
TI  - Metastatic endometrial carcinoma resulting in orbital apex compression.
AB  - A 63-year-old woman presented subacutely with signs of orbital apex and cavernous
      sinus disease in the setting of widespread, untreated metastatic carcinoma of the
      uterus. MRI revealed a destructive lesion of the left sphenoid wing with
      compression of the orbital apex and with possible extension in the cavernous
      sinus. The underlying diagnosis was confirmed with repeat endometrial biopsy,
      revealing well-differentiated endometrial adenocarcinoma. Given the supporting
      clinical evidence for metastatic disease and the radiologic characteristics of
      the lesion, the decision was made to not perform a confirming orbital biopsy.

PMID- 17519677
TI  - Re: "Laterality of periocular basal cell carcinomas in relation to driving
      practices in Philadelphia, PA, U.S.A.".

PMID- 17519678
TI  - Laterality of periocular basal cell carcinomas in relation to driving practices
      in Philadelphia, PA, U.S.A.

PMID- 17519679
TI  - Re: "minimally invasive conjunctivodacryocystorhinostomy with Jones tube".

PMID- 17519681
TI  - Re: "congenitally enlarged extraocular muscles: can congenital thyroid eye
      disease exist in a euthyroid infant?".

PMID- 17519682
TI  - Defining the tear trough.

PMID- 17519684
TI  - Misdiagnosis in chronic canaliculitis.

PMID- 17519685
TI  - Quantifying upper eyelid laxity in symptomatic floppy eyelid syndrome by
      measurement of anterior eyelid distraction.

PMID- 17519686
TI  - Iatrogenic giant fornix syndrome of the lower eyelid.

PMID- 17519688
TI  - Temporal flap variations for craniofacial reconstruction.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Describe the anatomy of the temporal region. 2. Identify the types and
      possible indications of the temple group flaps to be selected depending on the
      defects, and then raise the flap safely for reconstruction. 3. Predict and manage
      successfully the potential complications of surgery. BACKGROUND: Good harmony of
      color and texture with surrounding tissues, thinness and adequate pliability,
      good alignment, obliteration of the cavities, and minimal donor-site morbidity
      are the main features of an ideal flap to be used in the reconstruction of
      craniofacial defects. Despite the numerous local, regional, and free flaps that
      have been described, to date, there has not yet been an ideal flap. The authors
      discuss the reconstruction alternatives presented by the temporal site and its
      outcomes. METHODS: The temporal group flaps can be raised using one or more
      tissues based on the superficial temporal artery and its branches, depending on
      the defect site and nature. They can be designed as axial skin flaps consisting
      of transposition or V-Y island flaps, composite flaps including more than one
      tissue, and chimeric flaps involving both the temple skin and temporal fascia
      based on the two distal branches of the superficial temporal artery. RESULTS: The
      temporal region is a good donor site for closure of craniofacial defects, by
      means of its rich vascular network and almost all types of tissue, including
      skin, fascia, muscle, galea, calvarial bone, and periosteum. The charm of this
      region has gradually increased as clinical experiences have advanced and its
      anatomy has been better understood. CONCLUSIONS: The authors discuss the history,
      anatomy, surgical dissection techniques, and potential complications and their
      management of temporal flaps.

PMID- 17519689
TI  - Cancer risk among Los Angeles women with cosmetic breast implants.
AB  - BACKGROUND: As the first generation of women who received cosmetic breast
      implants ages, questions remain about cancer risk. This study is an update of the
      Los Angeles Augmentation Mammaplasty Study and examines cancer risk among women
      with long-term exposure to breast implants. METHODS: The authors conducted a
      record linkage cohort study of patients with cosmetic breast implants by
      abstracting from records of the private practices of 35 board-certified plastic
      surgeons in Los Angeles County, California. They included 3139 Caucasian women
      who received cosmetic breast implants between 1953 and 1980. Spanish-surnamed
      women, nonresidents of Los Angeles County, and patients with prior subcutaneous
      mastectomy or breast cancer were excluded. Cancer outcomes through 1994 were
      ascertained through record linkage with the Los Angeles County Cancer
      Surveillance Program. RESULTS: With a mean follow-up period of 15.5 years, 43
      cases of breast cancer were observed, compared with 62.6 expected, based on Los
      Angeles County population-based incidence rates (standardized incidence ratio,
      0.69; 95% CI, 0.50 to 0.93). Significant increases were observed for cancer of
      the lung and bronchus (standardized incidence ratio, 2.14; 95% CI, 1.42 to 3.09)
      and vulvar cancer (standardized incidence ratio, 3.47; 95% CI, 1.39 to 7.16).
      CONCLUSIONS: The breast cancer results of this study are consistent with the
      previous reports of the Los Angeles study as well as with several other long-term
      cohort studies. Lung cancer has previously been found to be increased in this
      cohort and also in some, but not most, other studies. The increased risk of vulva
      cancer has previously been observed in this cohort and just one other.

PMID- 17519690
TI  - Changing trends in recipient vessel selection for microvascular autologous breast
      reconstruction: an analysis of 1483 consecutive cases.
AB  - BACKGROUND: Over the years, the authors' preferred recipient vessels for
      microvascular autologous breast reconstruction have changed from the
      thoracodorsal to the internal mammary vessels. METHODS: From 1994 to 2004, 1483
      microvascular autologous breast reconstructions were performed in 1168 patients
      at the authors' institution. Potential factors involved in the selection of the
      recipient vessels were evaluated and compared between the thoracodorsal and
      internal mammary groups. Rates of recipient vessel unusability and flap-related
      complications were also analyzed and compared between the two groups. RESULTS:
      The mean patient age was 48 years, and the mean follow-up time was 1.5 years. The
      vessel conversion rate was 2.8 percent for the thoracodorsal group and 1.9
      percent for the internal mammary group. Preoperative radiotherapy and previous
      axillary node dissection were significantly associated with thoracodorsal vessel
      conversion (odds ratios, 4.7 and 2.6, respectively). The overall flap-related
      complication rate (12.6 percent versus 8.6 percent) and specific flap-related
      complications, including flap loss (2.6 percent versus 3.8 percent), vessel
      thrombosis (3.7 percent versus 5.0 percent), fat necrosis (4.5 percent versus 2.6
      percent), infection (0.7 percent versus 0.7 percent), and hematoma (1.6 percent
      versus 1.9 percent), were comparable between the two groups, but the flap seroma
      rate was significantly higher in the thoracodorsal group (4.0 percent versus 0.7
      percent; odds ratio, 4.2). CONCLUSION: In the authors' experience, use of
      internal mammary vessels is safe, with low rates of vessel conversion and flap
      related complications.

PMID- 17519691
TI  - Blood transfusion and risk of metastatic disease or recurrence in patients
      undergoing immediate TRAM flap breast reconstruction: a clinical study and meta
      analysis.
AB  - BACKGROUND: The transfusion of blood products has a known immunomodulatory effect
      that may affect cancer recurrence. The present study examined whether blood
      transfusion is an independent risk factor for recurrence or development of
      metastatic disease among patients undergoing immediate breast reconstruction with
      a transverse rectus abdominis musculocutaneous (TRAM) flap. METHODS: Records of
      103 patients who underwent mastectomy and immediate reconstruction with a TRAM
      flap between 1991 and 2001 were reviewed. A logistic regression analysis was used
      to identify independent risk factors for metastasis or recurrence. For the meta
      analysis, all English-language studies regarding blood transfusion and breast
      cancer recurrence were reviewed, and 2 x 2 contingency tables were constructed
      from which a summary relative risk was calculated. RESULTS: There were 57 free
      and 35 pedicle TRAM flaps. Forty-nine patients (48 percent) received
      perioperative transfusion of nonautologous blood. Twenty patients (19 percent)
      experienced metastatic disease or local recurrence. Follow-up ranged from 4 to 14
      years (mean, 6.7 years). There was a higher observed rate of adverse outcome in
      patients who received transfusion, but this was not statistically significant (p
      = 0.90). Of the 11 articles identified by the meta-analysis, eight used a
      regression analysis controlling for the effect of stage and nodal status. The
      summary relative risk in these studies was 1.03 (95% CI, 0.90 to 1.26).
      CONCLUSIONS: Perioperative blood transfusion does not seem to be an independent
      risk factor for metastasis or cancer recurrence in patients undergoing TRAM flap
      reconstruction. The observed correlation in this and prior studies may be due to
      the effect of other, more significant factors, such as tumor stage and nodal
      status.

PMID- 17519692
TI  - Psychological factors predict patient satisfaction with postmastectomy breast
      reconstruction.
AB  - BACKGROUND: This prospective study examined the contribution of psychological
      factors to the prediction of patient satisfaction with postmastectomy breast
      reconstruction surgery. METHODS: Women presenting for breast reconstruction were
      administered presurgical psychological inventories. Measures of affective
      distress, depressive symptoms, anxiety, somatization, and somatic preoccupation
      were obtained from standardized inventories. At 1-year (n = 295) and 2-year (n =
      205) follow-up, subjects completed ratings of their satisfaction with both the
      general and aesthetic results of surgery. RESULTS: After controlling for
      sociodemographic variables and both surgical procedure type and timing, multiple
      linear regression analyses indicated that at 1-year follow-up preoperative
      measures of affective distress, depression, somatization, and somatic anxiety
      predicted less general satisfaction with surgical outcome, while presurgical
      levels of affective distress, depression, anxiety, somatization, and somatic
      anxiety predicted decreased aesthetic satisfaction. At 2-year follow-up, only
      preoperative affective distress retained a significant association with lowered
      general satisfaction with reconstructive surgery. In addition, at 2-year
      reassessment, aesthetic quality of surgical outcome was inversely related to all
      the presurgical psychological variables. CONCLUSIONS: Affective distress and
      somatic preoccupation negatively influence patient satisfaction with both
      aesthetic and general outcomes associated with postmastectomy breast
      reconstruction. Presurgical psychological screening and counseling of selected
      women who are being considered for breast reconstruction may be advisable to
      enhance patient satisfaction with reconstructive surgery.

PMID- 17519694
TI  - The effect of closed-suction drains on the incidence of local wound complications
      following tissue expander/implant reconstruction: a cohort study.
AB  - BACKGROUND: The purpose of this investigation was to evaluate the effect of
      drains on complications, including infection, seroma, and hematoma formation, in
      patients undergoing exchange of a temporary expander for a permanent breast
      implant. METHODS: A review of all tissue expander/implant breast reconstructions
      performed at a single center from 1997 to 2004 was undertaken. Two patient
      cohorts were identified: patients who underwent exchange of their expander to a
      permanent implant with the use of closed-suction drains and patients who
      underwent the exchange procedure without the use of drains. The incidence of
      infection, seroma, and hematoma formation was determined for each cohort. Chi
      square and two-sample t tests were performed for categorical and continuous
      variables, respectively. RESULTS: A total of 2446 exchange procedures in 1863
      patients were performed. In 1495 reconstructions (1165 patients), drains were
      placed after the exchange procedure; in 951 reconstructions (698 patients), no
      drains were used. There was no difference in the overall rate of complications
      following the exchange procedure with or without the use of drains (p = 0.886).
      Specifically, there was no difference in the incidence of infection necessitating
      implant removal in the presence of drains compared with that in the absence of
      drains (p = 0.585). Similarly, there was no significant difference in the rate of
      hematoma/seroma formation with or without the use of drains (p = 0.742).
      CONCLUSION: The use of periprosthetic, closed-suction drains after exchange of a
      temporary expander for a permanent breast implant does not affect the incidence
      of perioperative complications, including infection, seroma, and hematoma
      formation.

PMID- 17519695
TI  - Immunosuppressive effect of tryptophan metabolites in composite tissue
      allotransplantation.
AB  - BACKGROUND: Hand transplantations have intensified immunological research into
      composite tissue allotransplantation to induce tolerance. Pregnancy is a
      successful, natural model of immunological tolerance. The enzyme indoleamine 2,3
      deoxygenase plays an important role by catabolizing the amino acid tryptophan.
      The resulting metabolites have been shown to be immunosuppressive. The effect of
      tryptophan metabolites has not been investigated in vascularized organ
      transplantation before. In this study, the authors applied to composite tissue
      allotransplantation what nature has developed for pregnancy, and examined the
      immunosuppressive effect of tryptophan metabolites in a model of hind limb
      transplantation. METHODS: Thirty-three allogeneic hind limb transplantations in
      the rat (Lewis --> Brown-Norway) were performed in three groups. Group A (n = 12)
      received no immunosuppression, group B (n = 13) received tryptophan metabolites
      (kynurenine and 3-hydroxyanthranilic acid) locally and systemically, and group C
      (n = 8) served as a control group receiving FK506. The timing of rejection was
      assessed by clinical observation. RESULTS: Rejection of the allogeneic hind limb
      occurred on average 6.58 days after transplantation in group A (no
      immunosuppression) and after 8.15 days in group B (tryptophan metabolites).
      Rejection was significantly delayed (log-rank test, p < 0.01). No rejection was
      seen with application of FK506 during the follow-up period of 21 days.
      CONCLUSIONS: For the first time, tryptophan metabolites have been applied in
      vascularized composite tissue allotransplantation and showed a significant
      immunosuppressive effect. These promising first results need further dose-effect
      and toxicological studies to increase the still limited immunosuppressive effect
      and define the clinical role these metabolites may play in the future.

PMID- 17519696
TI  - Can proximity of the occipital artery to the greater occipital nerve act as a
      cause of idiopathic greater occipital neuralgia? An anatomical and histological
      evaluation of the artery-nerve relationship.
AB  - BACKGROUND: The purpose of this study was to clarify whether proximity of the
      occipital artery to the greater occipital nerve can act as a cause of occipital
      neuralgia, analogous to the contribution of intracranial vessels due to
      compression in cranial nerve neuralgias, represented by trigeminal neuralgias due
      to compression of the trigeminal nerve root by adjacent arterial loops. METHODS:
      Twenty-four suboccipital areas in cadaver heads were studied for anatomical
      relationships between the occipital artery and the greater occipital nerve, with
      histopathological assessment of the greater occipital nerve for signs of
      mechanical damage. RESULTS: The occipital artery and greater occipital nerve were
      found to cross each other in the nuchal subcutaneous layer, and the latter was
      constantly situated superficial to the former at the cross point. An indentation
      of the greater occipital nerve due to the occipital artery was observed at the
      cross point in all specimens. However, histopathological examination did not
      reveal any findings of damage to nerves, even in specimens with atherosclerosis
      of the occipital artery. CONCLUSIONS: Although the present study did not provide
      direct evidence that the occipital artery contributes to occipital neuralgia at
      the point of contact with the greater occipital nerve, the possibility still
      cannot be precluded, because the occipital artery may be palpable in areas
      corresponding to tenderness of the greater occipital nerve. Further studies,
      including clinical cases, are needed to clarify this issue.

PMID- 17519698
TI  - Cranial suture response to stress: expression patterns of Noggin and Runx2.
AB  - BACKGROUND: Current theory on normal cranial suture fusion entrusts the dura with
      the regulatory role. Studies suggest that the dura responds to stress with
      changes in gene expression. Noggin (bone morphogenetic protein inhibitor)
      expression is decreased in normal (rat and mouse) cranial suture fusion, but its
      role in craniosynostosis and the response to stress has not been studied.
      METHODS: Posterior frontal (fusing) and sagittal (patent) rat cranial sutures
      were held static, oscillated, or distracted for 10 days in an organ culture
      microdistraction device beginning at 5 days of age (n = 30 sutures, or 10 sutures
      per group). The percentage of fusion equaled the score received for bony closure.
      Noggin, Runx2, and alkaline phosphatase expression was localized by
      immunohistochemistry for all groups. RESULTS: Both the posterior frontal and
      sagittal sutures demonstrated a significant (p < 0.05) increase in fusion
      percentage with oscillation relative to the static control. Noggin was not
      expressed in the fusing posterior frontal suture but was expressed in the
      normally patent sagittal suture. Conversely, Runx2 was expressed in the posterior
      frontal suture but not in the sagittal suture. However, when a mechanical stress
      was applied, both the posterior frontal and sagittal sutures expressed Runx2 but
      not Noggin, as in the static fusing suture. CONCLUSIONS: The application of
      mechanical stress to cranial sutures results in fusion of both the posterior
      frontal suture and the normally patent sagittal suture. Runx2 is expressed but
      Noggin is not expressed. Thus, mechanical stress influences sutural fusion and
      may play a role in craniosynostosis.

PMID- 17519699
TI  - Effect of venous superdrainage on a four-territory skin flap survival in rats.
AB  - BACKGROUND: In a previous report, the authors demonstrated that distal arterial
      supercharging is more effective at increasing flap survival. There is no doubt of
      the benefit of arterial augmentation in flap surgery, but the effect of venous
      superdrainage is still controversial. The purpose of this study was to
      investigate how venous augmentation could generate larger flap survival areas
      with different superdrainage positions in rats. METHODS: A four-territory skin
      flap, developed by the authors, was used. Forty rats were divided into four
      groups, as follows: group 1, flaps based only on the deep circumflex iliac artery
      and vein; group 2, flaps superdrained with the ipsilateral superficial inferior
      epigastric vein; group 3, flaps superdrained with the contralateral superficial
      inferior epigastric vein; and group 4, flaps superdrained with the contralateral
      deep circumflex iliac vein. On the fourth postoperative day, the flaps were
      assessed by measurements of necrosis and survival areas. Vascular changes
      produced by venous augmentation were evaluated angiographically. RESULTS:
      Compared with group 1 (mean flap survival, 37.8 +/- 5.0 percent), the flap
      survival areas were significantly greater in the superdrainage flap groups (group
      2, 57.4 +/- 6.5 percent, p < 0.001; group 3, 72.4 +/- 21.3 percent, p < 0.001,
      and group 4, 89.2 +/- 18.8 percent; p < 0.001). Angiographic assessment of the
      flaps revealed dilatation of the choke vein between the territories and
      reorientation of dilated veins along the long axes of the flaps. CONCLUSIONS:
      This study demonstrates that venous augmentation is also effective for increasing
      flap survival, and the distal procedure is more effective than the proximal
      procedure in arterial supercharging.

PMID- 17519700
TI  - Postoperative medical complications--not microsurgical complications--negatively
      influence the morbidity, mortality, and true costs after microsurgical
      reconstruction for head and neck cancer.
AB  - BACKGROUND: Immediate reconstruction of composite head and neck defects using
      free tissue transfer is an accepted treatment standard. There remains, however,
      ongoing debate on whether the costs associated with this reconstructive approach
      merit its selection, especially considering poor patient prognoses and the high
      cost of care. METHODS: A retrospective review of the last 100 consecutive
      patients undergoing microsurgical reconstruction for head and neck cancer by the
      two senior surgeons was performed to determine whether microsurgical
      complications or postoperative medical complications had the more profound
      influence on morbidity and mortality outcomes and the true costs of these
      reconstructions. RESULTS: Two patients required re-exploration of the
      microsurgical anastomoses, for a re-exploration rate of 2 percent, and one flap
      failed, for a flap success rate of 99 percent. The major surgical complication
      rate requiring a second operative procedure was 6 percent. Sixteen percent had
      minor surgical complications related to the donor site. Major medical
      complications, defined as a significant risk to the patient's life, occurred in 5
      percent of the patients, but there was a 37 percent incidence of "minor" medical
      complications primarily caused by pulmonary problems and alcohol withdrawal.
      Postsurgical complications almost doubled the average hospital stay from 13.5
      days for those patients without complications to 24 days for patients with
      complications. Thirty-six percent of the true cost of microsurgical
      reconstruction of head and neck cancer was due to the intensive care unit and
      hospital room costs, and 24 percent was due to operating room costs. Postsurgical
      complications resulted in a 70.7 percent increase in true costs, reflecting a
      prolonged stay in the intensive care unit and not an increase in operating room
      costs or regular hospital room costs. CONCLUSION: Postoperative medical
      complications in these elderly, debilitated patients related to pulmonary
      problems and alcohol withdrawal were statistically far more important in
      negatively affecting the outcomes and true costs of microsurgical reconstruction.

PMID- 17519701
TI  - Histological comparison between young and aged specimens of the Oriental lower
      eyelid using sagittal serial sections.
AB  - BACKGROUND: Understanding the anatomy of the lower eyelid, including the effect
      of aging, assists in blepharoplasty. METHODS: After celloidin was embedded, 30
      mum-thick serial sagittal sections from the medial to the lateral canthus were
      prepared from two Japanese left lower eyelid specimens obtained from a young
      cadaver and an old cadaver. A comparative study was then performed. RESULTS: The
      orbicularis oculi muscle was divided into three portions. Each muscular portion
      was transformed by aging. The fascia group that maintained the orbicularis oculi
      muscle was observed. Particularly, the fasciae in the upper and lower portions
      were termed the "upper fascia" and "lower fascia," respectively. These fasciae
      were generically referred to as "suborbicularis retaining fasciae." The
      suborbicularis retaining fasciae relaxed with aging. Fat tissue was observed in
      front of the orbital septum and was termed "preseptal adipose tissue." This area
      was most sensitive to deep pressure, because the retaining fascia hardly exists
      here; it almost disappears with aging. The retinacula cutis connected the
      orbicularis oculi muscle and the skin in parallel; their palisade structure was
      not clear in the aged specimen. In both specimens, the tarsal muscle did not
      unite with the tarsus, and the muscle fiber was enlarged at the lateral border of
      the tarsus. CONCLUSION: Lower eyelid aging changes were involved in the
      transformation of the three parts of the orbicularis oculi muscle, the relaxation
      of the suborbicularis retaining fasciae, the disappearance of the preseptal
      adipose tissue area due to orbital fat herniation, and the indistinctness of the
      palisade structure of the retinacula cutis.

PMID- 17519702
TI  - The expanded supraclavicular flap, prefabricated with thoracoacromial vessels,
      for reconstruction of postburn anterior cervical contractures.
AB  - Mentosternal contractures are well-known complications after burns, scald
      injuries, and injuries with acid or lye. These contractures may cause severe
      deformities that are both functionally and aesthetically crippling.
      Reconstruction of the neck requires the transfer of large flaps of thin, pliable
      skin to optimally match the texture and color of the recipient region. With the
      introduction of free tissue transfer, the availability of flaps for
      reconstruction of large neck defects has greatly increased. Unfortunately, many
      of these flaps are bulky and are not well matched to the thin and pliable skin of
      the neck. This article introduces the expanded supraclavicular flap prefabricated
      with the thoracoacromial vessels for reconstruction of anterior cervical
      contractures. Their anatomic location, length, and arc of rotation make the
      thoracoacromial vessels an excellent choice for prefabricating the
      supraclavicular skin for its subsequent interpolation into the anterior neck.
      Skin expansion in the donor region not only allows coverage of the larger unit of
      the anterior neck but also modifies the morphologic characteristics of the
      transferred flap through capsule formation and fatty tissue atrophy, which is
      beneficial for obtaining an optimal neck reconstruction.

PMID- 17519704
TI  - Axial bilobed superficial temporal artery island flap (tulip flap):
      reconstruction of combined defects of the lateral canthus including the lower and
      upper eyelids.

PMID- 17519705
TI  - A better template for microtia reconstruction: the waterproof, mirror-image
      digital photograph of the contralateral ear.

PMID- 17519706
TI  - Free flap reexploration: indications, treatment, and outcomes in 1193 free flaps.
AB  - BACKGROUND: Microvascular free tissue transfer is a reliable method for
      reconstruction of complex surgical defects. However, there is still a small risk
      of flap compromise necessitating urgent reexploration. A comprehensive study
      examining the causes and methods of avoiding or treating these complications has
      not been performed. The purpose of this study was to review the authors'
      experience with a large number of microvascular complications over an 11-year
      period. METHODS: This was a retrospective review of all free flaps performed from
      1991 to 2002 at Memorial Sloan-Kettering Cancer Center. All patients who required
      emergent reexploration were identified, and the incidence of vascular
      complications and methods used for their management were analyzed. RESULTS: A
      total of 1193 free flaps were performed during the study period, of which 6
      percent required emergent reexploration. The most common causes for reexploration
      were pedicle thrombosis (53 percent) and hematoma/bleeding (30 percent). The
      overall flap survival rate was 98.8 percent. Venous thrombosis was more common
      than arterial thrombosis (74 versus 26 percent) and had a higher salvage rate (71
      versus 40 percent). Salvaged free flaps were reexplored more quickly than failed
      flaps (4 versus 9 hours after detection; p = 0.01). There was no significant
      difference in salvage rate in flaps requiring secondary vein grafting or
      thrombolysis as compared with those with anastomotic revision only. CONCLUSIONS:
      Microvascular free tissue transfer is a reliable reconstructive technique with
      low failure rates. Careful monitoring and urgent reexploration are critical for
      salvage of compromised flaps. The majority of venous thromboses can be salvaged.
      Arterial thromboses can be more problematic. An algorithm for flap exploration
      and salvage is presented.

PMID- 17519707
TI  - Differential effect of burn injury on fibroblasts from wounds and normal skin.
AB  - BACKGROUND: Although there are well-recognized fluctuations in the systemic
      concentration of cytokines and growth factors after burn injuries, the effect on
      wound-healing potential in patients is not well understood. The objective of this
      study was to characterize the proliferation rate and response of wound and dermal
      fibroblasts to cytokines in burn patients compared with normal subjects. METHODS:
      Polyvinyl alcohol sponges were implanted subcutaneously in normal subjects and
      burn patients soon after admission. Sponges were removed for wound fibroblast
      explantation after 12 days. At the same time, a small piece of skin was excised
      for dermal fibroblast explantation. Fibroblast proliferation was then quantified
      after exposure to 10% fetal bovine serum, 1% fetal bovine serum, interleukin-1,
      transforming growth factor-beta1, or interferon-alpha2b. RESULTS: Normal
      subjects' dermal fibroblasts (n = 7) exposed to 10% fetal bovine serum showed
      significantly increased proliferation relative to normal subjects' wound
      fibroblasts (n = 3) (p < 0.0005), burn patients' dermal fibroblasts (n = 5) (p <
      0.05), and burn patients' wound fibroblasts (n = 5) (p < 0.0001). Burn patients'
      dermal fibroblast proliferation was also significantly augmented relative to burn
      patients' wound fibroblasts (p < 0.005); however, there was no significant
      difference between the two wound fibroblast types. Proliferation of burn
      subjects' fibroblasts was significantly enhanced with the addition of interleukin
      1 and significantly decreased for dermal fibroblasts with interferon-alpha2b. A
      significant elevation of proliferation with transforming growth factor-beta1 was
      seen only with burn patients' dermal fibroblasts. CONCLUSIONS: The data suggest
      that systemic mediators markedly alter the proliferation potential of dermal
      fibroblasts but not of wound fibroblasts. However, the wound environment
      substantially alters both the proliferation rate and the responsiveness of
      fibroblasts to cytokines. Thus, the data support the value of using wound
      fibroblasts during preliminary in vitro experiments to investigate wound-healing
      modification by cytokine manipulation.

PMID- 17519709
TI  - Monitoring the changes in intraparenchymatous venous pressure to ascertain flap
      viability.
AB  - BACKGROUND: Disruption of venous outflow can lead to tissue necrosis. Thrombosis
      of a venous channel at the coaptation site in instances of free tissue transfer
      could cause death of the transplanted tissues. Although various techniques have
      been used to monitor the viability of transferred tissues, there has been no
      technique designed specifically to check the flow within and the patency of the
      venous channel. The authors have devised an approach with which to monitor the
      changes in venous pressure in a composite tissue transferred by means of
      microsurgical technique for bodily reconstruction. METHODS: The status of the
      venous system in various composite tissue grafts was monitored at the time of
      surgery or for 3 days after the completion of surgery by placing a small-caliber
      catheter in the vein within the transferred tissue. A total of 52 patients
      participated in the study. RESULTS: The venous pressure noted in grafts with a
      patent venous channel remained constant within a range between 0 and 35 mmHg.
      Venous insufficiency was detected in three of the 52 cases, with unmistakable
      findings of an elevated venous pressure of over 50 mmHg. CONCLUSIONS: The
      technique of measuring the venous pressure by means of an indwelling venous
      catheter to monitor changes was found to accurately assess the patency of the
      venous channel and, by inference, the viability of the transferred tissue. No
      morbidity was associated with the technique.

PMID- 17519710
TI  - Free functioning muscle transfer for lower extremity posttraumatic composite
      structure and functional defect.
AB  - BACKGROUND: Traumatized lower extremities may present not only composite soft
      tissue defects but also flexor and/or extensor loss. Free functioning muscle
      transfer can provide composite structural and functional restoration. METHODS:
      From 1996 to 2004, 19 patients with lower extremity injuries whose lesions
      exhibited composite soft-tissue damage, with or without bone defects, and certain
      accompanying functional disabilities were allocated to study groups on the basis
      of impression, as follows: group I, open fracture IIIB (n = 10); group II,
      neglected compartment syndromes [open IIIB (n = 4) and open IIIC (n = 1)]; and
      group III, crush injuries (n = 4). Free flap resurfacing was indicated for these
      lesions. Fifteen patients underwent free functioning muscle transfer; source
      muscles were the rectus femoris (n = 3), rectus femoris with anterolateral thigh
      flap (n = 5), and gracilis (for ankle dorsiflexion) (n = 7). Two patients
      underwent composite rectus femoris and vascular iliac crest for ankle
      dorsiflexion and segmental tibial defect reconstruction. Two received rectus
      femoris muscle and anterolateral thigh flaps for posterior compartment defect and
      quadriceps defect reconstruction, individually. RESULTS: Two patients required
      reexploration; salvage was successful in only one, with below-knee amputation
      necessary in the other. Skin grafts were needed for partial skin paddle necrosis
      (n = 3) or remaining skin defect (n = 2). Functioning muscle reinnervation failed
      in four cases, with one individual undergoing ankle fusion, two people electing
      ambulation with stiff ankles, and one person using an orthosis. In the sample
      population, range of motion varied and was related to the severity of injury and
      the extent of skin grafting on the distal musculotendinous portion. Less function
      was exhibited in the compartment syndrome group (group II). CONCLUSION:
      Functioning muscle transfer can be performed posttraumatically in lower limbs
      with composite soft-tissue and motor-unit defects, resulting in acceptable
      functional results and reliable limb salvage.

PMID- 17519711
TI  - The distally based sural musculoneurocutaneous flap for treatment of distal
      tibial osteomyelitis.
AB  - BACKGROUND: The treatment of distal tibial osteomyelitis represents a challenge
      for orthopedic and plastic surgeons. The affected tissues should be debrided and
      good vascularized tissue should cover the defect, but the option of a muscle flap
      covering the area is limited. Free flaps are used but require longer operating
      time and experience with microsurgery, may result in donor-site morbidity, and
      sometimes add bulky tissue to the area. The authors present their experience with
      a sural musculoneurocutaneous flap for the treatment of chronic osteomyelitis of
      the distal tibia. METHODS: Over a 2-year period, nine distally based sural
      musculoneurocutaneous flaps were used in the treatment of chronic osteomyelitis
      of the distal tibia. Four patients had comorbid conditions (smoking, diabetes
      mellitus, venous insufficiency, or obesity). The clinical aspect was represented
      by drainage sinuses located in the distal part of the tibia. Five patients had
      postsurgical scars on the lateral malleolar region and one had medial and lateral
      malleolar scarring. Three patients had an Ilizarov device at the time of wound
      coverage. RESULTS: All wounds were closed successfully. Dehiscence surrounding
      the flap was encountered in a single case that was attributable to inadequate
      bone debridement; this flap was raised to allow extending the debridement, and a
      local medial fasciocutaneous flap completed wound coverage. Distal tip necrosis
      of the flap was encountered in two cases. CONCLUSIONS: The sural
      musculoneurocutaneous sural flap was successfully used for treatment of distal
      tibia osteomyelitis. Although it is believed that lateral malleolar scars might
      compromise the flap, the flaps in the authors' series survived. This flap can
      also be applied to patients with external fixators without removing the
      apparatus.

PMID- 17519712
TI  - The soft-tissue frame.

PMID- 17519713
TI  - Simultaneous surgical release of ipsilateral pronator teres and carpal tunnel
      syndromes.
AB  - BACKGROUND: Because of overlapping symptoms, carpal tunnel syndrome is sometimes
      diagnosed and a more proximal site of compression may be missed. Incomplete
      relief following carpal tunnel surgery may be caused by the failure to identify
      the second site of compression. METHODS: A retrospective review was performed on
      61 patients who were diagnosed as having both carpal tunnel syndrome and pronator
      teres syndrome of the ipsilateral median nerve. Besides precise medical history
      and physical evaluation, nerve conduction velocity studies and electromyography
      were performed. All patients but two had ipsilateral endoscopic carpal tunnel
      release and pronator teres release. Results after surgery were clinically
      assessed and evaluated as follows: complete relief, partial relief, or no relief.
      RESULTS: Postoperative evaluation resulted in 39 of 61 patients (64 percent)
      experiencing complete relief. Thirteen patients (21 percent) had partial relief.
      Eight of these patients were secondarily diagnosed with more proximal
      compression. Five of them had thoracic outlet compression syndrome, and three of
      them had cervical radiculopathy. For five patients, no specific reason was found
      for experiencing only partial relief. Nine patients (15 percent) had no
      significant relief. Among those patients, four were diagnosed with thoracic
      outlet compression syndrome and two with cervical radiculopathy; for three
      patients, the authors found no specific reason for failure. CONCLUSION: The main
      benefit of using this protocol in this selected group of patients is to shorten
      total morbidity time and to avoid exposure of the patient to two operations
      instead of one.

PMID- 17519714
TI  - Ropivacaine versus lidocaine in digital nerve blocks: a prospective study.
AB  - BACKGROUND: Ropivacaine is a relatively new long-acting amide local anesthetic.
      Since its introduction in 1996, it has been used for subcutaneous infiltration;
      epidural, intrathecal, and peripheral nerve block surgery; and postoperative
      analgesia. However, it has never been used for digital blocks. This prospective,
      randomized, double-blind study compares the digital block results following the
      administration of 2.5 ml of 0.75% ropivacaine solution and 2.5 ml of 2% lidocaine
      solution. METHODS: From March of 1999 to March of 2001, 70 adult patients who
      underwent immediate reconstruction for traumatic injuries of the digits were
      prospectively randomized into two groups. Group A (n = 35) received 2.5 ml 0.75%
      ropivacaine and group B (n = 35) received 2.5 ml of 2% lidocaine for digital
      anesthesia. Onset time of anesthetic action, duration of anesthesia, time until
      first postoperative requirement for pain medication, and digital-brachial artery
      systolic blood pressure index were recorded and evaluated. Local vascular effects
      were observed visually. RESULTS: No side effects were observed. Lidocaine had the
      quickest onset of anesthesia, with a mean time of 1.3 minutes (range, 1 to 2.7
      minutes). Ropivacaine had a mean onset time of 4.5 minutes (range, 3.5 to 5.5
      minutes). The mean duration of postoperative anesthesia for lidocaine was 2.4
      hours (range, 1.4 to 4 hours), compared with 21.5 hours for ropivacaine and less
      requirement for analgesics during the first 24 postoperative hours (p < 0.05)
      (range, 19 to 23 hours). No significant difference was found between the digital
      brachial artery systolic blood pressure index of group A compared with group B.
      CONCLUSIONS: Ropivacaine can be used effectively as a local anesthetic for
      digital nerve blocks. It can be used for prolonged operations (>1.5 hours)
      without additional injections and can provide long-lasting postoperative
      analgesia.

PMID- 17519715
TI  - The transverse radial artery forearm flap.
AB  - BACKGROUND: In an attempt to improve the versatility of the radial forearm flap,
      a new design was developed: the transverse radial artery forearm flap. METHODS:
      The transverse radial artery forearm flap is designed elliptically in the distal
      palmar forearm with the long axis oriented transversely parallel to the wrist.
      The donor defect is closed by a V-shaped flap, which is elevated as a
      fasciocutaneous flap based on the ulnar artery by V-Y advancement. This second
      flap allows defect coverage without the need for a skin graft. From March of 1994
      to February of 2005, the authors treated 39 patients with this flap. Free flaps
      were used in 36 patients and three patients were operated on with reverse
      pedicled flaps. RESULTS: Twenty-five patients had head and neck defects, 11
      patients had defects of the distal foot or great toe, and three patients had hand
      defects. In 13 cases, an osteocutaneous flap was elevated, and three flaps were
      transferred as sensate flaps. Maximum flap dimensions were 10 x 6 cm. The longest
      vascular pedicle in this series was 20 cm. All flaps survived. Except for two
      cases of delayed healing, no complications occurred at the donor site.
      CONCLUSIONS: The transverse radial artery forearm flap is more versatile than the
      conventional radial flap, with the additional advantage of a long vascular
      pedicle. Its design allows for harvest of a piece of radial bone, which is
      pedicled on a completely different portion of the radial artery than the skin
      paddle. Thus, the setting of the bony portion can be chosen liberally. Donor-site
      morbidity is reduced, and the result is aesthetically pleasing.

PMID- 17519716
TI  - Wilhelm Heinrich Erb, M.D. (1840 to 1921): a historical perspective on Erb's
      palsy.
AB  - Erb's palsy is well known to physicians across medical specialties, and its
      clinical manifestations present a formidable challenge to reconstructive
      surgeons. Although the condition is well established, knowledge pertaining to its
      namesake, Wilhelm Heinrich Erb, is rather obscure in the existing scientific
      literature. Erb was influential not only through his description of classic
      brachial plexus palsy involving the superior (or upper) roots, but also by his
      indelible contributions to our understanding of peripheral nerve physiology, deep
      tendon reflexes, and the muscular dystrophies. Erb's contributions to medicine
      transcend specialty boundaries. In this article, the authors seek to convey his
      scientific achievements and the character of the man through translation of his
      German manuscripts. These texts, complemented by the existing English literature,
      provide a unique perspective on Wilhelm Heinrich Erb's contribution to medicine.
      The authors will also emphasize his role in describing and clarifying the nature
      of Erb's palsy.

PMID- 17519717
TI  - Biomechanical strain and morphologic changes with age in rat calvarial bone and
      sutures.
AB  - BACKGROUND: The role of calvarial sutures in transmitting biomechanical forces
      within the head is unclear. METHODS: To examine the biomechanical characteristics
      of sutures, the authors measured bite force changes in rats and tested for
      alterations in strain across intrafrontal and sagittal sutures and within
      parietal bone with age. To understand the effects of suture fusion on strain
      distribution in the head, the authors measured percentage fusion of the
      intrafrontal sutures with age (n = 6 per age group). The masticatory muscles in
      anesthetized 9-, 24-, and 70-day-old rats (n = 15 per group) were bilaterally
      stimulated. Stacked delta rosette gauges were fixed across the intrafrontal
      sutures and sagittal suture, or on the parietal bone. Strain and bite force were
      measured with a bite force transducer positioned at the incisors. RESULTS: Bite
      force increased significantly (p < 0.05) with age (9-day-old rats, 72.6 +/- 20
      gf; 24-day-old rats, 707.3 +/- 150 gf; 70-day-old rats, 2425.6 +/- 255 gf). Some
      significant differences were found between the volume and direction of strain
      among sites and age groups. Compressive strains of 230 microepsilon on average
      were found across the intrafrontal sutures at all ages. In contrast, tensile
      strains less than 180 microepsilon on average were found across the sagittal
      sutures of 9- and 24-day-old rats, increasing to 940 microepsilon on average at
      day 70. Tensile strains in parietal bone tended to be less than 150 microepsilon.
      CONCLUSIONS: The timing of sutural closure and patterns of transsutural strain do
      not suggest that strain patterns contribute to initial fusion in the intrafrontal
      sutures. Differences in strain are likely related to changes in rat skull
      kinetics with growth, perhaps resulting from fusion of the intrafrontal sutures.

PMID- 17519719
TI  - Therapeutic strategy for the triad of acquired anophthalmic orbit.
AB  - BACKGROUND: In treating patients with anophthalmic orbits, it is essential to
      achieve a long-lasting natural appearance and comfortable retention of eye
      prostheses. In 1992, the authors developed a therapeutic strategy based on a
      simple algorithm for treating the three common symptoms of acquired anophthalmic
      orbit: severe eye socket contracture is surgically treated with a radial forearm
      free flap transfer, upper lid depression is treated with lipoinjection, and lower
      lid retraction is treated with an auricular cartilage graft. METHODS: From 1992
      to 2004, 18 acquired anophthalmic orbits (11 enucleated and seven exenterated)
      were treated at Kobe University Hospital based on the authors' therapeutic
      strategy. Aesthetic outcomes were evaluated according to patient and surgeon
      satisfaction. RESULTS: Sixteen patients underwent auricular cartilage grafts,
      eight received radial forearm free flap transfers, and seven were treated with
      lipoinjection. Optional revisional surgery was carried out in four cases. The
      aesthetic outcome was assessed as good in six patients, moderate in eight
      patients, and poor in four patients; the last four had undergone total
      maxillectomy with orbital exenteration or had eyelid defects because of previous
      cancer surgery. CONCLUSIONS: The authors' therapeutic strategy for acquired
      anophthalmic orbit is simple and, with slight modification, fitting for most
      cases, although it necessitates innovative surgery in cases with orbital rim
      and/or eyelid defects.

PMID- 17519721
TI  - A three-dimensional evaluation of postoperative swelling following orthognathic
      surgery at 6 months.
AB  - BACKGROUND: Advances in three-dimensional technology have enabled applications
      for the clinical setting to be created and used in routine diagnosis, treatment
      planning, and patient education. The objectives of this prospective clinical
      trial were to determine the volume changes associated with facial swelling
      following orthognathic surgery. METHODS: Twelve subjects requiring orthognathic
      surgery were recruited for the study. Laser scanned images of the subjects were
      obtained under a reproducible, controlled environment with two laser-scanning
      devices assembled as a stereo pair. Three-dimensional laser scans were recorded
      over six time periods, as follows: T1, presurgical scan; T2, 1 day
      postoperatively; T3, 1 week postoperatively; T4, 1 month postoperatively; T5, 3
      months postoperatively; and T6, 6 months postoperatively. RESULTS: The results
      showed a clinical difference in the mean shell deviations between bimaxillary and
      single-jaw orthognathic surgery. Furthermore, the results suggest that the mean
      volume of swelling was reduced by approximately 60 percent within the first month
      after surgery. Finally, the amounts of swelling following surgery were greater in
      bimaxillary cases. The recovery in the swelling was also faster in this group of
      patients. CONCLUSIONS: Three-dimensional imaging has opened up new avenues of
      patient care and treatment evaluation. The results have shown that the laser
      scanning device and the method described are a reliable and accurate measure of
      facial swelling following surgery.

PMID- 17519722
TI  - Maxillary expansion using transpalatal distraction in patients with unilateral
      cleft lip and palate.
AB  - BACKGROUND: The goal of this study was to evaluate prospectively the use of a
      transpalatal distractor for surgically assisted rapid palatal distraction
      osteogenesis in the treatment of severe unilateral maxillary constriction of
      patients with cleft lip and palate following alveolar bone grafting. METHODS: The
      authors analyzed the clinical and radiographic data of eight patients with
      unilateral cleft lip and palate. Follow-up examinations were performed at 1, 3,
      6, and 12 months. RESULTS: All of the patients had satisfactory palatal expansion
      and correction of the dental crossbite without major complications. None of the
      children in this study were noncompliant with the prescribed duration of the
      active distraction period. CONCLUSIONS: Surgically assisted rapid palatal
      distraction osteogenesis using a transpalatal distractor results in a high rate
      of success in correcting maxillary transverse width discrepancies and dental
      crossbite and offers a harmonious maxillary arch shape in patients with
      unilateral cleft lip and palate.

PMID- 17519723
TI  - The role of functional orthodontic stress on implants in residual alveolar cleft.
AB  - BACKGROUND: The most widely accepted protocol for alveolar cleft reconstruction
      is repair during the mixed dentition stage (age, 9 to 11 years), before eruption
      of the canine teeth. Alveolar bone grafting should not be considered as an
      isolated therapy but always as an integrated part of comprehensive orthodontic
      treatment. METHODS: The authors evaluate the results of transitional secondary
      osteoplasty, comparing the use of autogenous cancellous bone versus heterogenetic
      implants, in patients with unilateral complete clefts who did or did not undergo
      orthodontic treatment. From 1990 to 1994, 48 patients aged between 9 and 11 years
      with unilateral alveolar cleft underwent alveolar grafting by transitional
      secondary osteoplasty. In 30 patients (group A), autogenous cancellous bone was
      used, and in 18 patients (group B), a heterogenetic implant consisting of
      demineralized bone powder containing bone morphogenetic protein and
      hydroxylapatite was used. RESULTS: Twenty-two patients in group A and 12 patients
      in group B underwent orthodontic treatment. After 10 to 12 years of follow-up,
      the clinical and radiographic examinations revealed that the best alveolar bone
      repair results were obtained using autologous bone graft in association with
      orthodontic treatment. Also, in the patients who underwent heterogenetic
      implantation, the orthodontic treatment clearly improved the quality of the
      osteoplasty. CONCLUSIONS: The essential conditions for a successful osteoplasty
      include meticulous operative technique and orthodontic treatment. The latter
      plays an essential role at several stages of development in children with clefts.
      The "functional stress" on the autologous or heterogenetic implant exerts a
      decisive influence on the quality and volume of the osteoplasty, preventing
      progressive resorption.

PMID- 17519724
TI  - The fat compartments of the face: anatomy and clinical implications for cosmetic
      surgery.
AB  - BACKGROUND: Observation suggests that the subcutaneous fat of the face is
      partitioned as distinct anatomical compartments. METHODS: Thirty hemifacial
      cadaver dissections were performed after methylene blue had been injected into
      specified regions. Initial work focused on the nasolabial fat. Dye was allowed to
      set for a minimum of 24 hours to achieve consistent diffusion. Dissection was
      performed in the cadaver laboratory using microscopic and loupe magnification.
      RESULTS: The subcutaneous fat of the face is partitioned into multiple,
      independent anatomical compartments. The nasolabial fold is a discrete unit with
      distinct anatomical boundaries. What has been referred to as malar fat is
      composed of three separate compartments: medial, middle, and lateral temporal
      cheek fat. The forehead is similarly composed of three anatomical units including
      central, middle, and lateral temporal-cheek fat. Orbital fat is noted in three
      compartments determined by septal borders. Jowl fat is the most inferior of the
      subcutaneous fat compartments. Some of the structures referred to as "retaining
      ligaments" are formed simply by fusion points of abutting septal barriers of
      these compartments. CONCLUSIONS: The subcutaneous fat of the face is partitioned
      into discrete anatomic compartments. Facial aging is, in part, characterized by
      how these compartments change with age. The concept of separate compartments of
      fat suggests that the face does not age as a confluent or composite mass.
      Shearing between adjacent compartments may be an additional factor in the
      etiology of soft-tissue malposition. Knowledge of this anatomy will lead to
      better understanding and greater precision in the preoperative analysis and
      surgical treatment of the aging face.

PMID- 17519726
TI  - Blepharoplasty in the post-laser in situ keratomileusis patient: preoperative
      considerations to avoid dry eye syndrome.
AB  - BACKGROUND: The authors used a retrospective case series to describe the
      increased frequency of dry eye syndrome in patients who have undergone both laser
      in situ keratomileusis and blepharoplasty. METHODS: The authors reviewed records
      from six patients who required surgical correction for exposure keratopathy
      previously treated by both laser in situ keratomileusis and blepharoplasty.
      RESULTS: All six patients developed significant exposure keratopathy
      postoperatively requiring surgical intervention. Four patients had blepharoplasty
      followed by laser in situ keratomileusis, and two patients had laser in situ
      keratomileusis followed by blepharoplasty. Symptomatic dry eye symptoms followed
      the second procedure 1 week to 4 months later. Surgical correction of eyelid
      malposition and lagophthalmos markedly improved symptoms. CONCLUSIONS: Patients
      with a history of laser in situ keratomileusis contemplating blepharoplasty are
      at higher risk of developing postoperative dry eye syndrome. Surgeons performing
      these procedures should perform thorough preoperative evaluation and surgical
      planning to minimize this potential complication.

PMID- 17519727
TI  - The influence of brow shape on the perception of facial form and brow aesthetics.
AB  - BACKGROUND: Previous studies have described the ideal shape of the aesthetic
      brow. These studies were based on fashion models, who typically have ideal oval
      faces. In people with different facial shapes, makeup artists modify brow shape
      to give the illusion of an oval shape. The purpose of this investigation was to
      compare the classically described ideal brow to the modified brow for each facial
      shape. METHODS: The faces of five models were morphed into round, square, oval,
      and long facial shapes. The eyebrows were digitally removed. A makeup artist drew
      the brows specifically for each facial shape. In a second set of prints, the brow
      shape was based on the previously published criteria. Seventy-eight people were
      asked which face they believed was more aesthetic. RESULTS: There was no
      significant difference between the classic and the modified eyebrow in the oval
      or round facial shapes. In the square and long facial shapes, the modified brow
      was found to be more attractive in 62.7 percent and 58.7 percent of the subjects,
      which is statistically significant (p < 0.05). CONCLUSIONS: The ideal brow may
      differ from the classic description when applied to the long or square face. In
      long faces, a flatter brow may give the illusion of fullness. In the square face,
      an accentuated lateral curvature may help soften the angles of the face. It may
      be difficult to achieve these modifications surgically, but it is important to be
      aware of the effect that brow shape has on facial shape.

PMID- 17519728
TI  - The results of surgical excision and adjuvant irradiation for therapy-resistant
      keloids: a prospective clinical outcome study.
AB  - BACKGROUND: There is no consensus on the best way to treat keloids, because
      adequate studies on this subject are sparse. Surgical excision in combination
      with radiotherapy is considered the most efficacious treatment available in
      severe keloids following the International Clinical Recommendations on Scar
      Management. Unfortunately, the recommendations are mainly based on retrospective
      studies that do not define recurrence. METHODS: The authors evaluated the
      recurrence rate of therapy-resistant keloids treated with excision followed by
      radiotherapy (1200 Gy in three or four fractions). The minimum follow-up period
      was 12 months. The therapeutic outcome was judged as recurrence (elevation of the
      lesion not confined to the original wound area) or nonrecurrence. An evaluation
      of the outcome of the scars was obtained by using the Patient and Observer Scar
      Assessment Scale. RESULTS: Twenty-one patients with 32 keloids were evaluated.
      The recurrence rate was 71.9 percent after a mean follow-up period of 19 months.
      CONCLUSIONS: This high recurrence rate suggests that radiotherapy might be less
      efficacious than suggested by other studies. On the basis of the authors'
      results, surgical excision combined with radiotherapy should be reserved as a
      last resort in the treatment of therapy-resistant keloids.

PMID- 17519729
TI  - The two-dermal-flap umbilical transposition: a natural and aesthetic umbilicus
      after abdominoplasty.
AB  - BACKGROUND: The aesthetic and natural appearance of the transposed umbilicus
      after abdominoplasty is a key factor to the overall result and satisfaction of
      patient and surgeon alike. In this article, the authors present a technique in
      umbilical transposition that creates a natural-appearing umbilicus. METHODS: The
      skin in the neoumbilical position is deepithelialized and incised in the midline,
      thus creating two dermal flaps that are sutured down to the abdominal fascia,
      thereby creating a natural periumbilical concavity, inconspicuous scars, and a
      tension-free closure, resulting in a decreased chance for cicatricial umbilical
      scarring. Twenty patients underwent umbilical transposition during abdominoplasty
      with this technique between 2003 and 2005. RESULTS: Both patient and surgeon
      satisfaction were very high, with three senior surgeons changing their surgical
      technique after being introduced to that described in this article. One
      complication culminated in partial skin dehiscence early in our experience when
      deep dermal sutures were not used for skin closure. CONCLUSION: The technique
      described is simple, safe, and easily learned, and results in a very satisfying
      aesthetic and natural-appearing umbilicus in patients after abdominoplasty.

PMID- 17519730
TI  - Sedation analgesia during office-based plastic surgery procedures: comparison of
      two opioid regimens.
AB  - BACKGROUND: The combination of sedative and analgesic drugs is increasingly being
      used during minimally invasive surgery. The authors compared the clinical
      efficacy of two different fentanyl regimens, in combination with midazolam, for
      sedation analgesia in patients undergoing office-based plastic surgery procedures
      under local anesthesia. METHODS: One-hundred patients were randomized into two
      groups of 50 subjects each. Group F1 received a fentanyl bolus of 0.7 microg/kg
      before infiltration with local anaesthetics; group F2 received the same bolus
      plus 0.6 microg/kg fentanyl every 45 minutes. All patients received a midazolam
      bolus of 0.05 mg/kg plus continuous infusion 0.08 mg/kg per hour. RESULTS: High
      quality analgesia was obtained in every group, without significant differences
      between the two fentanyl regimens. Group F2 was associated with lower
      intraoperative mean blood pressure and SpO2 values compared with group F1. No
      differences were detected between the two groups in perioperative side effects or
      postoperative pain. CONCLUSION: Higher doses of opioid did not improve the
      quality of perioperative patient comfort but acted synergistically with the
      sedative drugs, amplifying the hemodynamic and respiratory side effects.

PMID- 17519731
TI  - Long-lasting and permanent fillers: biomaterial influence over host tissue
      response.
AB  - BACKGROUND: The purpose of this study was to attempt to understand why some
      injectable fillers produce frequent ill effects and some do not, by reviewing the
      available agents and analyzing them through the knowledge of biomaterial studies,
      which show clearly what type of reactions can be expected according to the
      chemical used. METHODS: A study of long-lasting and permanent fillers was
      performed in an attempt to understand the specific reactions induced by each
      agent. Agents were then compared with manufacturers' allegations and published
      data on complications. RESULTS: All the available products have a potential for
      complications. However, the difference between the normal healing process and
      true inflammatory granuloma must be established. For a volume effect, the
      implant, although deep, should induce the smallest inflammatory reaction, to
      avoid any long-term side effects. Particulate implants with porous or irregular
      surfaces are potentially more reactive than spherical, smooth-surface particles.
      Gels and oils have a potential for fragmentation, and each droplet will start a
      new inflammatory phase. For a superficial treatment, is seems better to use a
      "passive" filler, which should have no inflammatory reaction. The problem remains
      for combined indications: volume and smoothing, deep and superficial. After
      hyaluronic acid injections in areas previously treated with a nonresorbable
      agent, severe inflammatory granulomas have appeared, and it is not possible to
      state whether they are attributable to the new product, even a resorbable one, or
      to reactivation of the sleeping reaction from the previous implant. CONCLUSION:
      There is an obvious need for serious, precise, and objective studies on most of
      the available fillers, which have not been properly scientifically studied on
      human skin.

PMID- 17519732
TI  - Autologous fat transfer for facial recontouring: is there science behind the art?
AB  - BACKGROUND: Clinical use of autologous fat grafts for facial soft-tissue
      augmentation has grown in popularity in the plastic surgery community, despite a
      perceived drawback of unpredictable results. METHODS: The authors' review of the
      literature and their current techniques of autologous fat transfer focused on (1)
      the donor site, (2) aspiration methods, (3) local anesthesia, (4) centrifugation
      and washing, (5) exposure to cold and air, (6) addition of growth factors, (7)
      reinjection methods, and (8) longevity of fat grafts. RESULTS: Clinical
      experience and basic science data showed a slight preference for the following:
      harvesting abdominal fat with "nontraumatic," blunt cannula technique,
      preparation by means of centrifugation without washing or addition of growth
      factors, and immediate injection of small amounts of fat by means of multiple
      passes. Quantitative evidence of clinical fat survivability and predictability of
      volume restoration does not exist, yet reports of patient satisfaction with this
      procedure do. Clinicians report the need for revisionary procedures to optimize
      results. CONCLUSIONS: Although there is an increased trend in replacement of soft
      tissue volume with autologous fat transfer, the literature fails to provide
      definitive evidence of fat survival. A large-scale clinical assessment using
      three-dimensional volumetric imaging would provide useful outcome data.

PMID- 17519733
TI  - The Canadian plastic surgery workforce survey: interpretation and implications.
AB  - BACKGROUND: Few studies have monitored physician supply in Canada, and no studies
      have specifically examined the Canadian plastic surgery workforce. METHODS: In
      this study, data were gathered by three methods. A survey was distributed to all
      members of the Canadian Society of Plastic Surgeons in October of 2004. Opinions
      on the availability of plastic surgery services were solicited. A second survey
      that focused on demographics and workload was distributed in December of 2004.
      Finally, the locations of all Canadian trainees graduating between 1995 and 2005
      were reviewed. RESULTS: The response rate to the first survey was 42 percent.
      Seventy-eight percent of respondents felt that there was a shortage of plastic
      surgeons in their community. The response rate to the second survey was 40
      percent. Twenty-eight percent of respondents were within 5 years of retirement
      and 3.2 percent stated that they planned to emigrate by 2010. The mean waiting
      time for an elective consultation was 32 +/- 33 weeks. Review of all 179 plastic
      surgery graduates over the past 10 years revealed that 23 percent now practice
      outside of Canada. CONCLUSIONS: When these results are projected to the total
      workforce, they indicate that there will be a future shortage of plastic surgeons
      in Canada. To prevent a further deficit, there is a need to increase the number
      of plastic surgery trainees in Canada, to offer incentives for graduates to stay
      in Canada, and to possibly recruit more foreign-trained plastic surgeons to
      practice within Canada.

PMID- 17519734
TI  - Ethical approval of clinical studies, informed consent, and the Declaration of
      Helsinki: what you need to know.

PMID- 17519737
TI  - Soft-tissue response: is it a standing obstacle in distraction osteogenesis?

PMID- 17519738
TI  - Nonresective shrinkage of the septum and fat compartments of the upper and lower
      eyelids: a comparative study with carbon dioxide laser and Colorado needle.

PMID- 17519741
TI  - Mini face lift with suspension sutures: historical analysis of development and
      morphic resonance.

PMID- 17519743
TI  - Investigation of risk acceptance in facial transplantation.

PMID- 17519745
TI  - Use of an expanded temporoparietal fascial flap technique for total auricular
      reconstruction.

PMID- 17519746
TI  - Preservation of digital palmar veins to avoid venous congestion in heterodigital
      arterialized flaps.

PMID- 17519750
TI  - Staged versus simultaneous bilateral endoscopic carpal tunnel release: an outcome
      study.

PMID- 17519752
TI  - Hernia repairs in postbariatric patients.

PMID- 17519753
TI  - The "reverse" latissimus dorsi myocutaneous flap for reconstruction of the
      gluteal region.

PMID- 17519754
TI  - Free microdissected thin groin flap design with an extended vascular pedicle;
      thin anterolateral thigh perforator flap using a modified microdissection
      technique.

PMID- 17519755
TI  - Is there any need to localize the perforator of the anterolateral thigh flap?

PMID- 17519759
TI  - Full-thickness skin graft as a one-stage debulking procedure after free flap
      reconstruction for the lower leg.

PMID- 17519760
TI  - Effects of hyperbaric oxygen on peripheral nerves.

PMID- 17519761
TI  - Update on office-based surgery regulations in New York State.

PMID- 17519763
TI  - Pseudoaneurysm of the frontal branch of the superficial temporal artery: an
      unusual complication after the injection of botox.

PMID- 17519764
TI  - Functional lower lip reconstruction with a modification in McGregor flap
      technique.

PMID- 17519765
TI  - Prepositioning a closed negative-pressure drainage device in head and neck
      reconstruction.

PMID- 17519766
TI  - Avoiding donor-site complications with bilateral DIEP flaps in patients with
      subcostal scars.

PMID- 17519767
TI  - Areola reconstruction with local tissue.

PMID- 17519768
TI  - Staged upper extremity reconstruction with a pedicled parascapular flap and
      massive bone graft after a devastating airplane propeller accident.

PMID- 17519769
TI  - Intersecting the intersection: a reliable incision for the treatment of de
      Quervain's and second dorsal compartment tenosynovitis.

PMID- 17519770
TI  - Simple irrigation technique for microvascular surgery.

PMID- 17519771
TI  - Analyses of skin waste during excision of benign skin lesions: is the surgical
      ellipse cut necessary?

PMID- 17519772
TI  - Wound irrigation in the emergency room: a simple, effective method.

PMID- 17519773
TI  - Use of hyaluronan dressings following dermabrasion avoids escharectomy and
      facilitates healing in pediatric burn patients.

PMID- 17519774
TI  - The management of human bites with regard to blood-borne viruses.

PMID- 17519776
TI  - Perspectives in organ preservation.
AB  - Maintaining organ viability after donation until transplantation is critically
      important for optimal graft function and survival. To date, static cold storage
      is the most widely used form of preservation in every day clinical practice.
      Although simple and effective, it is questionable whether this method is able to
      prevent deterioration of organ quality in the present era with increasing numbers
      of organs retrieved from older, more marginal, and even non-heart-beating donors.
      This review describes principles involved in effective preservation and focuses
      on some basic components and methods of abdominal organ preservation in clinical
      and experimental transplantation. Concepts and developments to reduce ischemia
      related injury are discussed, including hypothermic machine perfusion. Despite
      the fact that hypothermic machine perfusion might be superior to static cold
      storage preservation, organs are still exposed to hypothermia induced damage.
      Therefore, recently some groups have pointed at the beneficial effects of
      normothermic machine perfusion as a new perspective in organ preservation and
      transplantation.

PMID- 17519777
TI  - Commentary on living donor liver transplantation with reduced monosegments for
      neonates and small infants.

PMID- 17519778
TI  - Pregnancy after organ transplantation: a report from the UK Transplant pregnancy
      registry.
AB  - BACKGROUND: Maternal and fetal complications in pregnancies after renal
      transplantation have been highlighted in several reports, but information on
      their main predisposing factors is limited. The U.K. Transplant Pregnancy
      Registry was established in 1997 to obtain detailed information on pregnancies in
      female organ transplant recipients across the U.K. METHODS: For each female
      kidney, liver, or cardiothoracic organ transplant recipient who had had a recent
      pregnancy, data on maternal and fetal factors and pregnancy outcomes were
      collected using forms completed by their transplant follow-up and obstetric
      units. For kidney transplant recipients, the factors that influence pregnancy
      outcome were studied using logistic regression, and the effect of pregnancy on
      graft function was analyzed. RESULTS: There were live births in 83%, 69%, and 79%
      of pregnancies in cardiothoracic organ, liver, and kidney recipients,
      respectively. In 50% of live births from renal patients, delivery was preterm
      (<37 weeks), with 83% of the preterm infants delivered via caesarean. Preterm
      delivery was associated with maternal drug-treated hypertension and impaired
      renal function. A matched case-control study showed no evidence of increased
      renal allograft loss after pregnancy. A univariate survival analysis, however,
      suggested an association between drug-treated hypertension during pregnancy and
      poorer postpregnancy graft survival. In patients with prepregnancy serum
      creatinine (SCr) >150 micromol/L, a trend toward increased postpregnancy SCr was
      identified. CONCLUSIONS: Pregnancy is likely to end in a live birth in a majority
      of organ transplant recipients. In patients with greater prepregnancy SCr and/or
      drug-treated hypertension during pregnancy, however, subsequent renal function
      may be adversely affected.

PMID- 17519779
TI  - Probrain natriuretic peptide and C-reactive protein as markers of acute
      rejection, allograft vasculopathy, and mortality in heart transplantation.
AB  - BACKGROUND: N-terminal probrain natriuretic peptide (NT-proBNP) and C-reactive
      protein (CRP) are useful in risk stratification of patients with congestive heart
      failure. They could also be markers of distinctly altered hormonal and
      immunological milieus, but the combined prognostic value of these biomarkers in
      heart transplant (HTx) recipients has not been assessed previously. METHODS: We
      sought to assess the individual and combined value of NT-proBNP and CRP as
      markers of acute rejection, cardiac allograft vasculopathy (CAV) and all-cause
      mortality in HTx recipients. We evaluated 101 patients for acute rejection and
      210 patients for CAV and all-cause mortality. Patients evaluated for rejection
      had serial endomyocardial biopsies and plasma sampling performed during the first
      year postHTx. All other patients had plasma samples taken upon inclusion at an
      annual visit. Median follow-up for CAV and all-cause mortality was 2.2 years and
      5.4 years, respectively. RESULTS: Altogether, 1131 biopsy procedures were
      performed, and increased NT-proBNP and CRP levels were not useful markers of
      acute cellular rejection. In total, 78 (37%) patients developed CAV, and 39 (19%)
      patients died. Neither biomarker was a predictor of CAV, but both were
      independent predictors of mortality. When combining both biomarkers, elevated
      levels of both NT-proBNP and CRP identified patients at highest risk for CAV (HR
      2.10, P=0.01) and all-cause mortality (HR 3.14, P=0.01). CONCLUSIONS: In HTx
      recipients, NT-proBNP and CRP are not useful as markers of acute cellular
      rejection during the first year postHTx, but combined analysis adds significantly
      to their predictive value for development of CAV and all-cause mortality.

PMID- 17519780
TI  - Plasma exchange and retransplantation in recurrent nephrosis of patients with
      congenital nephrotic syndrome of the Finnish type (NPHS1).
AB  - BACKGROUND: Recurrent nephrotic syndrome (NS) is a severe problem after renal
      transplantation in patients with congenital nephrotic syndrome of the Finnish
      type (NPHS1). The NPHS1 kidneys do not express nephrin, and antibodies against
      this major glomerular filter protein have been observed in NPHS1 children with
      recurrent NS. We evaluated here the use of plasma exchange (PE) therapy and
      kidney retransplantation in NPHS1 patients with recurrent NS and extended our
      studies on the pathogenesis of the recurrence. METHODS: Clinical data on 65 NPHS1
      patients who received 77 kidney transplants between the years 1986 and 2006 was
      collected. Serum anti-nephrin antibodies were assayed with an enzyme-linked
      immunosorbent assay method, and the kidney biopsy samples were evaluated by light
      microscopy and immunohistochemistry. RESULTS: Twenty-three episodes of recurrent
      NS occurred in 19 grafts of 13 NPSH1 patients homozygous for Fin-major mutation.
      Six retransplantations were performed to four NPHS1 patients, who lost their
      graft because of recurrent NS, and heavy proteinuria developed immediately in all
      cases. Although 73% of the patients had detectable serum anti-nephrin antibodies,
      the kidney biopsy findings were minimal. Introduction of PE alongside
      cyclophosphamide proved effective in the treatment of the proteinuric episodes
      (one graft loss out of nine). If remission was achieved, recurrent NS did not
      significantly deteriorate the long term graft function. CONCLUSIONS: The clinical
      and pathological data suggest that anti-nephrin antibodies effectively impair the
      glomerular function in kidney grafts of NPHS1 patients homozygous for Fin-major
      mutation. Plasma exchange is a useful adjunct to the treatment of the recurrent
      NS.

PMID- 17519781
TI  - Long-term renal transplant function in recipient of simultaneous kidney and
      pancreas transplant maintained with two prednisone-free maintenance
      immunosuppressive combinations: tacrolimus/mycophenolate mofetil versus
      tacrolimus/sirolimus.
AB  - BACKGROUND: It is not known how different steroid-free immunosuppressive
      combinations affect long-term kidney transplant function in recipients of
      simultaneous kidney and pancreas transplant (SPK). Here, we sought to evaluate,
      in SPK recipients, the impact on long-term renal allograft function of two Tac
      based prednisone-free maintenance immunosuppressive protocols: tacrolimus
      (Tac)/mycophonelate mofetil (MMF) versus Tac/ sirolimus (SRL). METHODS: In this
      single-center, retrospective, sequential study, we analyzed 59 SPK transplant
      patients with at median follow up of 5 years. All patients received induction
      therapy with thymoglobulin and maintenance immunosuppression with Tac/MMF (n=22)
      or Tac/SRL (n=37). There were no differences between the two groups in regards to
      age, gender, race, panel reactive antibodies, degree of mismatch, donor age,
      incidence of delay graft function, and Tac trough levels at different time points
      after transplantation. RESULTS: Kaplan-Meier patient survival at 6 years after
      transplantation was not statistically different between the two groups. Rate of
      ACR was similar. Kidney survival, even if not statistically significant, was
      better in the Tac/MMF group than in the Tac/SRL (90.7% vs. 70.7%, P=0.09). The
      slope of glomerular filtration rate decline per month at 5 years after
      transplantation was not statistically different between the two groups. Both
      groups had the same decline over time in glomerular filtration rate of 0.40+/
      0.06 mL/min/1.73/month. Pancreas survival at 6 years after transplantation was
      100% in both treatment groups. CONCLUSIONS: Our data suggest that, in SPK
      recipients, long-term kidney allograft survival and function are not
      statistically different. A trend toward an increased rate of renal allograft loss
      was found in the Tac/SRL-treated group.

PMID- 17519782
TI  - Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the
      diagnosis of invasive aspergillosis in lung transplant recipients.
AB  - BACKGROUND: The clinical utility of Platelia Aspergillus enzyme immunoassay (EIA)
      for galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) for the
      diagnosis of invasive aspergillosis (IA) in lung transplant recipients is not
      known. METHODS: BAL fluid samples from consecutive lung transplant recipients who
      underwent bronchoscopy were prospectively analyzed for GM. RESULTS: A total of
      333 BAL samples from 116 patients were tested. Invasive aspergillosis was
      documented in 5.2% (6/116) of the patients. Samples analyzed included 9 BALs from
      two patients with proven IA, 19 BALs from four patients with probable IA, and 305
      BALs from 110 patients without IA. At the index cutoff value of > or =0.5, the
      sensitivity was 60%; specificity was 95%, with positive and negative likelihood
      ratios of 14 and 0.41, respectively. Increasing the index cutoff value to > or
      =1.0 yielded a sensitivity of 60%, a specificity of 98%, and the positive and
      negative likelihood ratios of 28 and 0.40, respectively. Two of six patients with
      IA receiving antifungal prophylaxis had false-negative results. CONCLUSIONS: A
      Platelia EIA index cut-off > or =1.0 in the BAL fluid in a lung transplant
      recipient with a compatible clinical illness may be considered as suggestive of
      IA.

PMID- 17519783
TI  - Living donor liver transplantation with reduced monosegments for neonates and
      small infants.
AB  - BACKGROUND: In pediatric living donor liver transplantation, left lateral segment
      or monosegmental graft is used to overcome size discrepancies between adult
      donors and pediatric recipients. For neonates and extremely small infants,
      however, problems related to large-for-size graft are sometimes encountered even
      when using such grafts. The reduced monosegmental graft, in which the caudal part
      of the monosegmental graft is resected, has been introduced to address this
      problem. METHODS: Of 566 children who underwent transplant between June 1990 and
      September 2004, reduced monosegment living donor liver transplants were used for
      nine patients (median age, 144 days; median weight, 4.1 kg). This technique was
      used for infants with estimated graft-to-recipient weight ratio (GRWR) > or =4.0%
      when using the left lateral segment. RESULTS: Graft and patient survival was
      66.7%. GRWR was reduced from 7.45+/-2.70% to 3.39+/-0.89% using this
      modification. Transaminase levels at days 1 and 2 after transplantation were
      significantly higher in reduced monosegmental transplantation than in left
      lateral segmental transplantation. Hepatic artery thrombosis and portal vein
      thrombosis were observed in one case each. CONCLUSION: Reduced monosegmental
      living donor liver transplantation represents a feasible option for neonates and
      extremely small infants with liver failure.

PMID- 17519784
TI  - Role of lamivudine in the posttransplant prophylaxis of chronic hepatitis B virus
      and hepatitis delta virus coinfection.
AB  - BACKGROUND: Posttransplant combined lamivudine (LAM) and immunoglobulin (HBIg)
      prophylaxis is the gold standard in the case of single hepatitis B virus (HBV),
      but is still not recommended in the case of patients coinfected with hepatitis
      delta virus (HDV). METHODS: We compared two consecutive groups of chronic HDV
      carriers who survived >6 months after liver transplantation of the risk of
      recurrence, survival and HBIg requirements: 21 received passive prophylaxis (HBIg
      group) and 25 were treated with combined prophylaxis (LAM+HBIg group). The
      immunoprophylaxis schedule was the same in both groups: intramuscular HBIg
      targeted to maintain anti-HBs levels of >500 IU/L during the first 6
      posttransplant months and >200 IU/L thereafter. RESULTS: The mean length of
      follow-up in the two groups was significantly different (133 vs. 40 months;
      P<0.001). None of the patients in either group developed recurrent hepatitis, and
      the 3-year actuarial survival rate was 100% in both groups. During the first 6
      months, HBIg requirement was 38% lower in the LAM+HBIg group although similar
      anti-HBs target levels were maintained, leading to significantly lower costs
      (5,000 Euros in the first year and 500 Euros in the second). CONCLUSIONS: This is
      the first study of large and homogeneous cohort of long-term HDV coinfected liver
      transplant survivors showing the absence of HBV recurrence under combined
      prophylaxis. Although retrospective, our results suggest that combined anti-HBV
      prophylaxis should also be preferred to single immunoprophylaxis in patients with
      HDV coinfection because it allows significant cost savings in the first two
      posttransplant years.

PMID- 17519785
TI  - Corneal transplantations from donors with cancer.
AB  - BACKGROUND: Acceptance criteria for corneal donation in some eye banks include
      cadavers with active cancer, both solid and hematological. Such acceptance is
      based on the fact that the cornea is an avascular tissue and metastatic
      dissemination is extremely unlikely. METHODS: From a total of 588 corneal donors
      in the Sant Pau Tissue Bank (April 1999 to December 2003), 204 (34.7%) had an
      active malignancy or a history of malignancy. Of these, 177 had solid cancers and
      27 had hematological cancers. Cancer was active in 94.7% and 64% had metastatic
      dissemination. A histopathological study of the 408 eyes from these 204 donors
      was performed to rule out metastasis. A total of 325 corneas (79.7%) were
      transplanted and recipients were followed for an average of 64.1 months (SD 11.1,
      range 30-86). RESULTS: The incidence of ocular metastases in the 204 donors with
      malignancy was 1%, 0.6% for solid cancer, and 3.7% for malignant hematological
      disease. There was no tumor transmission in any of the 325 recipients.
      CONCLUSIONS: The incidence of ocular metastases in corneal donors with active
      malignancy is very low. Donor-recipient tumor transmission through corneal
      transplantation is highly improbable when the eyes are free of cancer.

PMID- 17519786
TI  - Inhibition of sonic hedgehog signaling reduces chronic rejection and prolongs
      allograft survival in a rat orthotopic small bowel transplantation model.
AB  - BACKGROUND: Although acute graft rejection can be successfully controlled by
      immunosuppressive agents, chronic rejection (CR), which is characterized by
      arteriosclerosis in the donor organ vessels, is a major hurdle to long-term
      allograft survival. Sonic hedgehog (Shh), a morphogen critical in embryogenesis,
      also promotes peripheral immunity, which prompted us to investigate if inhibition
      of Shh signaling could reduce CR and thereby enhance allograft survival. METHODS:
      In a rat orthotopic small bowel transplantation model, FK506 prevented acute
      rejection; however, recipients eventually lost their grafts by CR. Anti-Shh
      antibody or isotype control were administered to animals at day 30
      postoperatively. Graft survival, tissue fibrosis, vascular occlusion, and
      expression of vascular endothelial growth factor (VEGF) were investigated.
      RESULTS: Immunostaining revealed that Shh and the Hedgehog receptor Patched 1
      (Ptc1) are strongly expressed in CR grafts and that Ptc1 expression partially
      overlapped with that of ED-1, a macrophage marker. In contrast, only minimal
      expression of Shh and Ptc1 was detected in syngeneic grafts. Grafts survival was
      significantly prolonged after anti-Shh antibody treatment compared with the
      immunoglobulin G control (116 vs. 77.5 days). Collagen deposition and vascular
      occlusion in the mesentery were markedly reduced in recipients of the anti-Shh
      antibody. Specific transcripts and protein expression for VEGF, which was present
      mainly in the blood vessels, were reduced. CONCLUSION: In a rat small bowel
      transplantation model, anti-Shh antibody treatment reduced CR and prolonged graft
      survival. These beneficial effects of Shh treatment may occur partly by reducing
      VEGF expression in the blood vessels of the allografts.

PMID- 17519787
TI  - Suppression of alloreactivity and allograft rejection by SP600125, a small
      molecule inhibitor of c-Jun N-terminal kinase.
AB  - BACKGROUND: c-Jun N-terminal kinase (JNK) is reported to play crucial roles in T
      cell activation and differentiation, and SP600125 is a small molecule that
      inhibits JNK. The aim of this study was to examine immunosuppressive action of
      this compound. METHODS: Rat heterotopic heart transplantation, popliteal lymph
      node (PLN) hyperplasia bioassay and lymphocyte proliferation assay. RESULTS:
      SP600125 treatment reduced histological rejection, and dose-dependently extended
      median survival time of cardiac allografts from 7 days (vehicle) up to 20 days
      (40 mg/kg/day). Alloantigen-induced PLN hyperplasia was also inhibited by
      SP600125 in a similar fashion. SP600125 suppressed mixed lymphocyte reaction and
      OX52-positive lymphocyte proliferation (IC50: 1.5-5.7 microM). Thus, SP600125
      inhibits both T-lymphocyte expansion in vitro and T-cell-mediated alloimmune
      responses in vivo. In addition, SP600125 interacted with cyclosporine additively
      to prolong cardiac allograft survival. CONCLUSION: Our data provide the first
      evidence indicating the potential for JNK as a therapeutic target to inhibit the
      alloimmune response.

PMID- 17519788
TI  - Impact of cyclosporine upon emotional and social behavior in mice.
AB  - BACKGROUND: Cyclosporine induces psychological side effects but its mechanisms of
      action remain to be elucidated. METHODS: Mice were injected with cyclosporine (0,
      10, 60 mg/kg intraperitoneal) and indexes of both anxiety-related and social
      behaviors were examined. Release of serotonin and dopamine in the prefrontal
      cortex was also investigated by microdialysis. RESULTS: Intraperitoneal
      administration of cyclosporine increased cyclosporine concentrations in the blood
      and brains in mice. Cyclosporine administration at a higher-dose reduced motor
      activity, increased indexes of anxiety-related behavior, and decreased an index
      of social interaction. The administration reduced release of serotonin and
      dopamine in the prefrontal cortex. Clozapine administration abolished the reduced
      release of dopamine and partially restored the index of social behavior in
      cyclosporine-injected mice. CONCLUSIONS: This in vivo model suggests that
      cyclosporine at a high dose induced hypo-function of the prefrontal cortex as a
      result of reduced release of serotonin and dopamine, increased anxiety-related
      behavior, and disturbed social behavior. Clozapine partially restored an index of
      social behavior. The present findings are pathologically relevant in patients who
      take cyclosporine.

PMID- 17519789
TI  - Erythropoietin protects the kidneys against ischemia reperfusion injury by
      activating hypoxia inducible factor-1alpha.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury is closely associated with tissue
      damage in various organs, as well as in kidney transplants. Erythropoietin (EPO)
      has been shown to have a cytoprotective effect against hypoxia. We examined the
      effect of EPO against renal I/R injury and the underlying mechanism. METHODS:
      Human umbilical vein endothelial cells and human renal proximal tubular
      epithelial cells were cultured under hypoxic conditions with various EPO
      concentrations at 37 degrees C and examined the mechanism of cell proliferation
      by EPO. Moreover, to demonstrate the renoprotective effect in vivo, we treated
      Sprague-Dawley rats with 100 IU/kg EPO every 2 days for 2 weeks (a total of 6
      doses). One day after the last injection, the operations to produce renal I/R
      injury (bilateral renal occlusion for 60 min) were done, and rats were killed at
      the end of the reperfusion period (24 hr and 72 hr after reperfusion began).
      RESULTS: First, we demonstrated in vitro that EPO increased hypoxia inducible
      factor-1alpha (HIF-1alpha) expression and stimulated proliferation of both cells
      under hypoxic conditions. Next, we demonstrated in vivo that EPO treatment
      increased the number of HIF-1alpha-positive cells, and markedly induced the
      expression of vascular endothelial growth factor messenger RNA. Using
      pimonidazole, a molecular probe that detects hypoxia, we found that EPO markedly
      attenuated tubular hypoxia, and reduced the number of terminal transferase dUTP
      nick end labeling-positive apoptotic cells and alpha-smooth muscle actin-positive
      interstitial cells. CONCLUSIONS: We suggested a novel HIF-1alpha induction
      pathway by EPO under hypoxic conditions. Thus, EPO may protect the kidneys
      against ischemia reperfusion injury by activating HIF-1alpha.

PMID- 17519790
TI  - Polymorphisms of multidrug resistance gene (MDR1) and cyclosporine absorption in
      de novo renal transplant patients.
AB  - BACKGROUND: Several single nucleotide polymorphisms (SNPs) in the multidrug
      resistance (MDR1) gene may play a role in the interindividual variation of
      cyclosporine A (CsA) absorption in renal transplant patients. METHODS: An
      analysis of CsA absorption measured by the dose- and weight-adjusted 4 hr area
      under the time-concentration curve, AUC(0-4)/mg doseCsA/kg, was conducted on day
      3 after transplantation, in 69 de novo renal transplant patients who were
      genotyped for MDR1 SNPs. Follow-up pharmacogenomic analysis at 1 month
      posttransplant was performed utilizing dose- and weight-adjusted 2-hour postdose
      CsA concentration (C2). RESULTS: AUC(0-4)/mg doseCsA/kg was significantly higher
      (P=0.024) in (C/C)3435 individuals than in a grouped population of (C/T)3435 and
      (T/T)3435 patients on postoperative day 3. G2677T variants were not significantly
      correlated with CsA absorption (P=0.084). The number of C3435-G2677 haplotypes
      was the best predictor of CsA exposure. At 1 month posttransplant, no correlation
      was seen between MDR1 SNPs and CsA exposure. The frequency of wild-type variants
      for C3435T and G2677T were 61% and 77.6%, respectively. SNPs at G2677T and C3435T
      loci were found to be in linkage disequilibrium. CONCLUSIONS: MDR1 polymorphisms
      are associated with differences in CsA exposure only in the first posttransplant
      week.

PMID- 17519791
TI  - Complex arterial reconstruction for pancreas transplantation in recipients with
      advanced arteriosclerosis.
AB  - Pancreas transplantation can be very challenging in the recipient with iliac
      artery disease. In this report, we describe three techniques we have applied in
      these difficult situations and include demonstrative case reports. In principle,
      we believe that this is a problem that should be dealt with carefully to prevent
      further complicating the situation and should be resolved before bringing the
      allograft to the operative field in order to prevent prolonged warm ischemic
      times.

PMID- 17519792
TI  - Sirolimus conversion in liver transplant recipients with renal dysfunction: a
      prospective, randomized, single-center trial.
AB  - This pilot trial was designed to assess the safety and efficacy of SRL in liver
      transplant recipients with renal dysfunction. Forty patients with renal
      dysfunction (24-hr CrCl 40-80 mL/min) were randomized to be withdrawn from the
      calcineurin inhibitor (CNI) and receive sirolimus (SRL) or to continue CNI
      (control arm). Improvement in 24-hour CrCl was seen in the SRL arm at 3 months
      (75 mL/min SRL vs. 56 mL/min control, P=0.012), whereas at 12 months there was a
      trend toward improvement in the SRL arm (72 mL/min SRL vs. 58 mL/min control,
      P=0.09). Two patients, one in each arm, developed steroid-sensitive rejection.
      Side effects of SRL were limited and included hyperlipidemia requiring treatment
      (15%), pruritus (5%), and mouth sores (25%). In this trial, SRL-based
      immunosuppression was a safe alternative to CNI. Although early improvements were
      observed, withdrawing CNI and replacing it with SRL did not result in a
      statistically significant improvement in renal function at 12 months of follow
      up.

PMID- 17519793
TI  - Induction of regulatory T cells after prophylactic treatment with photopheresis
      in renal transplant recipients.
AB  - Extracorporeal photopheresis (ECP), originally used to treat cutaneous T-cell
      lymphoma, also has been applied to the therapy of transplant rejection. Our aim
      was to investigate the biologic response in two children who underwent kidney
      transplantation with ECP as prophylactic treatment. They received conventional
      immunosuppressive therapy and ECP immediately after transplantation: six
      applications over the course of 3 weeks. During a 12-month follow-up, the
      clinical course was favorable in both patients; renal histology was normal 6
      months after transplantation. When compared with four transplanted controls, the
      ECP-treated patients showed lower tumor necrosis factor-alpha serum levels in the
      short-term and a marked increase of Foxp3-positive T-regulatory cells. T
      regulatory cells were still higher than in the controls 1 year after
      transplantation. These preliminary results suggest that the addition of ECP to
      standard immunosuppressive therapy induces a tolerogenic shift in the immune
      system of kidney transplanted patients and may pave the way to preventing chronic
      rejection.

PMID- 17519794
TI  - A new preservation solution increases islet yield and reduces graft
      immunogenicity in pancreatic islet transplantation.
AB  - The aim of the study was to test a new preservation solution containing
      polyethylene glycol (S.C.O.T. solution) as pancreatic islet isolation medium both
      to increase the islet yield and to prolong the allograft survival. In a model of
      islet transplantation in diabetic mouse, islets were isolated with S.C.O.T. in
      experimental groups and with Hank's balanced salt solution (HBSS) in control
      groups. The use of S.C.O.T. solution improved the islet yield (596+/-27
      IEQ/pancreas) as compared to HBSS (456+/-11 IEQ/pancreas) (P<0.001). Allograft
      survival was prolonged in experimental group (17.3+/-4.3 days) versus controls
      (7.3+/-3.6 days) in a full mismatch combination (P<0.001) and in absence of
      recipient immunosuppression. The same prolongation (10 days) was also found in a
      strongly alloreactive transgenic combination. It is hypothesized that a
      transitory phenomenon of immunocamouflage of the graft surface antigens occurs,
      as shown by immunofluorescence studies. The use of this new solution could
      improve the results of islet transplantation in humans.

PMID- 17519795
TI  - A new model of corneal transplantation in the miniature pig: efficacy of
      immunosuppressive treatment.
AB  - Corneal allograft rejection is frequently studied in small rodent or rabbit
      models. To study mechanisms of rejection in a model that more closely mimics
      transplantation in humans, we performed orthotopic corneal transplantation in the
      miniature pig using a 7-mm diameter donor graft. Four groups of recipients were
      studied: 1) untreated naive, 2) untreated vascularized (high risk), 3) high-risk
      grafts treated by topical application of prednisolone, or 4) high-risk grafts
      treated with a combined systemic immunosuppression regime of oral prednisone,
      cyclosporine A, and mycophenolate mofetil. Both the clinical features and
      histological assessment of corneal graft rejection showed close similarities to
      graft rejection in humans. Interestingly, preliminary results indicated that
      topical steroid treatment was superior to systemic immunosuppression in
      significantly promoting graft survival. Thus, corneal transplantation in the pig
      represents an animal model most closely resembling corneal grafting in humans,
      and offers possibilities for testing various clinically applicable
      immunosuppressive treatments.

PMID- 17519796
TI  - Fatal human herpes virus 6 primary infection after liver transplantation.

PMID- 17519797
TI  - Reciprocal auxiliary partial liver transplant for inborn noncirrhotic metabolic
      diseases.

PMID- 17519798
TI  - Liver Transplantation From a Donor Affected by Marfan's Syndrome.

PMID- 17519799
TI  - Gender disparities in live kidney donation: fundamental moral differences?

PMID- 17519800
TI  - Long-term outcome of nephrotic syndrome in an allogeneic hematopoietic stem cell
      recipient without typical features of graft versus host disease.

PMID- 17519801
TI  - Successful treatment of invasive pulmonary aspergillosis after ABO-incompatible
      living donor liver transplantation under rapid steroid withdrawal protocol.

PMID- 17519802
TI  - Variation in sweating patterns: implications for studies of hot flashes through
      skin conductance.
AB  - OBJECTIVE: The literature of sweat physiology and population variation in
      response to heat stress suggests that variation in sweating patterns may affect
      the measurement of hot flashes. This study examined variation in sweating
      patterns in Puebla, Mexico, and Amherst, MA, and compared the levels of
      concordance between subjective and objective measures of hot flashes. DESIGN:
      Thirteen women in Puebla, Mexico, and 15 women in Amherst, MA, aged 45 to 61,
      completed surveys, body diagrams of heat flow during a hot flash, anthropometric
      measures, and the measurement of hot flashes through skin conductance monitoring.
      Hot flashes were measured through sternal (Mexico and Massachusetts) and nuchal
      (Mexico only) skin conductance. RESULTS: Mexican women were significantly more
      likely to describe the heat of hot flashes on the back of their neck (100% vs
      40%) and on their arms and/or hands (85% vs 40%) compared with women in
      Massachusetts. Hot flashes in the midback were associated with concordance
      between nuchal, but not sternal, measures of skin conductance and subjective
      report in Mexico. In comparing average scores for concordance between subjective
      and sternal measures of hot flashes, there was a higher mean score for true
      positives in Mexico (61% vs 29%, P=0.06) and a significantly higher mean score
      for false-negative measures in Massachusetts (57% vs 21%, P=0.04). CONCLUSIONS:
      Variation in rates of concordance between subjective and objective measures were
      not adequately explained by sweating patterns. Future studies should consider
      population variation in acclimatization and assess variation in the amount of
      sweat produced during a hot flash.

PMID- 17519803
TI  - Symptom groupings at midlife: cross-cultural variation and association with job,
      home, and life change.
AB  - OBJECTIVE: To examine how symptoms at midlife grouped together by factor analyses
      in four different countries and to examine whether life changes were associated
      with symptom frequencies. DESIGN: The Decisions at Menopause Study was a
      multisite study of women aged 45 to 55 drawn from the general population in the
      United States, Spain, Lebanon, and Morocco. Semistructured questionnaires
      collected demographic, reproductive, and lifestyle information, along with 4-week
      recalls of 25 symptoms. Factor analyses were performed using symptom frequency
      data from each country. Symptoms frequencies were examined by chi analysis in
      relation to job, home, and life changes. Regression scores for individual factors
      were examined as dependent variables in relation to menopause status and life
      change while controlling for demographic and reproductive variables. RESULTS: The
      intercorrelation among symptoms differed in country-specific ways, eg, hot
      flashes grouped with vaginal dryness and sexual symptoms in Spain, with general
      somatic symptoms in Morocco, and did not cluster with other symptoms in the
      United States or Lebanon. In chi2 analyses, household change, not job change, was
      associated with increased symptomatology in Spain. Job change was a significant
      predictor of the first symptom cluster in the United States (mental symptoms) and
      Spain (emotional symptoms). Home change was a significant predictor of the third
      (mental) symptom cluster in Spain. Life change was a significant predictor of
      symptom clusters in Spain and Morocco. CONCLUSIONS: Cross-population comparisons
      demonstrate variation in symptom clusters. Regression analyses showed how the
      variables that predict symptom groupings (eg, job change, marital status,
      menopause status, or level of education) also differed in country-specific ways.

PMID- 17519804
TI  - The origin of breast cancer.
AB  - Biological studies confirm that breast cancer is the result of an accumulation of
      a large number of individual genetic mutations that collectively alter elements
      of the complex internal signaling system of a cell. These aberrant genetic
      alterations, when assembled in a single breast cell, disrupt the control system
      to the extent that the cell functions autonomously in an erratic and irregular
      manner. Continual replication of a corrupted cell results in the formation of a
      colony of abnormal cells that may accumulate other aberrant mutations to
      eventually initiate cancer. What causes these mutations has been the topic of
      debate over a number of years, but because so many genetic alterations are
      involved, it is now conceded that one single factor could not possibly initiate
      all the changes. One plausible explanation involves a sequence of random,
      accidental, spontaneous mutations during normal stem cell replication. Some of
      these mutations may be an advantage to the host and their creation advances the
      functional ability of the breast, whereas abnormal mutations are usually deleted
      after activation of the complex apoptotic and inhibitory signaling system. When
      the defense system is corrupted, cells carrying the abnormal genes are able to
      avoid elimination, eventually passing abnormal mutations from one cell generation
      to the next. Accumulation of genetic abnormalities, over time, leads to
      development of a colony of cells that are pathologically abnormal. Biological
      studies confirm that cultured stem cells are capable of undergoing spontaneous
      mutations during mitosis, that sex hormones control the rate of mitosis, and that
      estrogen and progesterone therefore influence the rate that mutations occur.
      Accumulating the large number of mutations that eventually cause breast cancer
      can be achieved only if chromosomal abnormalities are carried from one generation
      of cells to the next to combine with genetic alterations generated spontaneously
      during stem cell mitosis.

PMID- 17519805
TI  - Knowledge of reproductive physiology and hormone therapy in 53- to 54-year-old
      Swedish women: a population-based study.
AB  - OBJECTIVE: To investigate knowledge of hormone therapy (HT), reproductive
      physiology, and menopause in a population of 53- to 54-year-old women. Further
      aims were to determine whether the knowledge differed between users and nonusers
      of HT and between groups with different levels of education. DESIGN: In 2003, all
      53- and 54-year-old women (N = 1,733) in Linkoping, Sweden, were sent a
      questionnaire containing questions about reproductive physiology related to
      menopause and HT. Answers from 73% of the women were analyzed. RESULTS: Swedish
      women had limited knowledge of HT, reproductive physiology, and menopause
      irrespective of HT use or educational level. Most of the women knew that hot
      flashes are common around menopause and decreasing estrogen production causes the
      menopause. They knew little about the effects of progestagens and the effects of
      HT on fertility. Women with low educational level were more likely to answer the
      questions by stating that they were unsure than did women with high educational
      level. Ever-users of HT knew more than never-users about risks and benefits of HT
      in relation to breast cancer and osteoporosis, and ever-users thought that the
      risks of thrombosis and myocardial infarction were lower than did never-users.
      CONCLUSIONS: Women need improved knowledge of the risks and benefits of HT as
      well as education about the reproductive system around menopause. This would
      probably better support and empower women to manage an important period of their
      lives.

PMID- 17519806
TI  - Cerebral inflammatory response after fetal asphyxia and hyperoxic resuscitation
      in newborn sheep.
AB  - Resuscitation with pure oxygen at birth after fetal asphyxia may aggravate brain
      damage by inducing pro-inflammation. The toll-like receptors (TLRs) may serve a
      pro-inflammatory role in hyperoxemia during ischemia-reperfusion. Sixteen near
      term fetal sheep (132-136 d) were subjected to 10 min of cord occlusion, delivery
      and mechanical ventilation with 100% O2 (n = 8), or 21% O2 (n = 8) for 30 min
      followed by normoxemia for 90 min. Eight sheep fetuses were delivered immediately
      with inspired O2 targeted at normoxemia for 120 min (controls). Levels and
      distributions of mRNAs for IL-1beta, TNF-alpha, IL-12p40, IL-18, IL-6, IL-10, IFN
      gamma, TLR-2, -3 and -4 in cerebral tissue at 2 h after birth were evaluated with
      real-time polymerase chain reaction (PCR) and in situ hybridization. Expressions
      of IL-1beta, IL-12p40, TLR-2, and TLR-4 were increased in cortex/subcortex after
      resuscitation with 100% O2 compared with 21% O2 (all p < 0.05) and to controls
      (all p < 0.05). Increased cellular expression of IL-1beta was localized to sub
      meningeal cortical layers and to sub-cortical white matter. Hyperoxic
      resuscitation at birth following fetal asphyxia induces a cerebral pro
      inflammatory response with an up-regulation of TLR-2 and -4. These may be early
      events leading to increased tissue damage after exposure to hyperoxemia at birth.

PMID- 17519807
TI  - [Techniques for giving information to people with cancer: between ethics and
      pragmatism].

PMID- 17519808
TI  - [Occupational exposure to low concentrations of carbon monoxide and sleep
      disordered breathing. A negative result].
AB  - INTRODUCTION: This study explored the possibility that occupational exposure to
      low concentrations of carbon monoxide (CO) could influence the synchronisation of
      upper airway and lower respiratory muscles and thus induce sleep disordered
      breathing. METHODS: Two hundred and thirty subjects exposed to between 1 and 5
      ppm (peaks up to 25 ppm) at work and one hundred and sixteen unexposed controls
      were studied with a protocol comprising anthropomorphic measurements and a self
      completed French translation of the Wisconsin Sleep Questionnaire. RESULTS: The
      two groups had similar anthropomorphic and lifestyle data with the exception that
      the exposed group were slightly younger (2.5 years). No differences were found in
      personal or family history, sleep related breathing disorder (snoring, breathing
      pauses etc) and disturbed sleep. CONCLUSIONS: Occupational exposure to low
      concentrations of CO do not seem to affect ventilatory drive and the
      synchronisation of upper airway and respiratory muscles during sleep. It should
      be recognised that these results were obtained by a relatively insensitive
      technique (questionnaire); a protocol including polysomnography applied to
      subjects exposed to higher concentrations of CO could lead to other conclusions.

PMID- 17519809
TI  - [Trends in hospital admissions for asthma in France, 1998-2002].
AB  - BACKGROUND: As the quality of asthma care influences hospital admission rates, we
      described hospitalizations for asthma and studied trends in admission rates in
      France from 1998 to 2002. METHODS: Using data from the French hospital
      information system, admissions for asthma were defined by the J45 or J46 codes
      (ICD-10) as primary diagnosis, and admissions for acute respiratory failure (ARF)
      associated with asthma by the J96.0 code as primary diagnosis and the J45 or J46
      codes as an associated diagnosis. Annual rates of admission adjusted for age and
      sex were calculated. RESULTS: During the study period, the adjusted asthma
      admission rate decreased by 5% per year (from 10.8/10,000 in 1998 to 8.6/10,000
      in 2002). A significant decrease was observed in children aged 10-14 years (
      5%/year) and in older people (from -7%/year in 15-19 years old to -9%/year in
      people aged 50 years or more), whereas no significant decrease was seen in
      youngest children (-2%/year in children aged 0-1 or 5-9 years, +0.1%/year in
      those aged 2-4 years). Although not statistically significant, an increase in
      admission rate for ARF associated with asthma was observed (+5%/year).
      CONCLUSION: Admission rates for asthma decreased between 1998 and 2002 in people
      aged 10 years and older. However, changes in coding practices or admission
      policies cannot be excluded and the extent to which the observed trends reflect
      changes in preventive care among patients with asthma remains to be assessed.

PMID- 17519810
TI  - [Incidence of individualized training on exercise-induced desaturation in COPD
      patients].
AB  - BACKGROUND: Exercise-induced desaturation is a well-described phenomenon in COPD
      patients during exercise assessments such as the six minute walk test (6MWT).
      Some of the pathophysiological mechanisms involved in this O2 desaturation could
      be modified by individualized exercise training as part of a pulmonary
      rehabilitation programme. The aim of this study was to determine the effect of
      pulmonary rehabilitation on O2 desaturation exhibited by COPD patients during a
      6MWT. METHODS: Twenty COPD patients (FEV1=61.1 +/- 3.2% predicted) who exhibited
      O2 desaturation before rehabilitation (mean 7.3 +/- 0.7% with a mean duration of
      5.3 +/- 0.1 min) participated. They performed four weeks of RP including
      individualized whole-body exercise training achieving a mean 9.3 +/- 0.27 hours
      per week of exercise tailored to their ventilatory threshold. RESULTS: Dyspnoea
      at the end of the test, ventilatory threshold and FEV1 were retained as
      correlates of desaturation before rehabilitation. After rehabilitation, 6MWT
      distance increased (p<0.01) with reduced dyspnoea (p<0.05). Two sub-groups were
      identified: persistent desaturaters (DS, n=13) and non-desaturaters group (NDS,
      n=7). There were no baseline differences between the two groups. After
      rehabilitation only the persistent desaturaters showed a significant increase in
      distance achieved during 6MWT associated with a reduced dyspnea (p<0.05). This
      group showed a mean O2 desaturation equal to 8.1 +/- 0.9% which persisted to 5 +/
      0.3 min. A tendency to a lower dyspnoea at the end of 6MWT performed before
      rehabilitation was observed in NDS compared with DS (p<0.058). CONCLUSION: It
      seems that responses to a pulmonary rehabilitation programme including
      individualized exercise training could act on O2 desaturation. Indeed 7 of 20
      (35%) COPD patients exhibiting O2 desaturation during a 6MWT showed no O2
      desaturation after rehabilitation programme while 13 on 20 (65%) do it.

PMID- 17519811
TI  - [Environmental factors for asthma severity and allergy: results from the EGEA
      study].
AB  - INTRODUCTION: EGEA (Epidemiological study on the genetics and environment of
      asthma, bronchial hyperresponsiveness and atopy), a case control and family study
      including 2048 individuals, was initiated to look for environmental and genetic
      risk factors for asthma. A synthesis of the results obtained since 2002 on
      phenotypic and environmental aspects of asthma severity and allergy are presented
      in this article. METHODS AND RESULTS: The results support a role for hormonal
      factors in asthma severity and in various allergic markers of asthma. A greater
      body mass index was related to a more severe asthma in women with early menarche.
      Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal
      dependent events in women (premenstrual asthma, menopause and oral contraceptive
      use) have been found. In asthmatics, exposure to agents known to be associated
      with occupational asthma, active and passive smoking were associated with an
      increased clinical asthma severity score. The study underlines the protective
      role of country living and exposure to pets in early life on allergy markers in
      adulthood, supporting the hygiene hypothesis. CONCLUSIONS: New hypothesis will be
      tested in the near future from the second stage of this survey.

PMID- 17519812
TI  - [Social and housing conditions of patients with chronic respiratory failure
      treated in the ANTADIR Federation].
AB  - INTRODUCTION: Chronic respiratory failure (CRF) has an impact on quality of life
      because of respiratory handicap. METHODS: The purpose of this study was to
      analyse the daily life and social activities of patients with CRF. A
      questionnaire was addressed to over 9000 patients being cared for in the ANTADIR
      homecare network, with over a 60% response rate. RESULTS: The data showed that
      patients were old, and frequently had comorbidity. The predominant diagnosis was
      chronic obstructive airways disease (COPD) and the number of women in this
      population continues to increase. Respiratory handicap led to a loss of autonomy,
      a reduction in social activity and mobility of patients, but the impact differed
      markedly according to the cause of the respiratory failure, as well as age and
      social class. A typological study of behavioural characteristics revealed three
      groups of patients with contrasting profiles. CONCLUSION: These results lead to
      recommendation for better management of social aspects of patient care in the
      ANTADIR network.

PMID- 17519813
TI  - [Pulmonary mucormycosis: difficulties in diagnosis and treatment].
AB  - INTRODUCTION: Mucormycosis is a rare opportunistic fungal infection due to
      filamentous fungi of the order Mucorales in the class Zygomycetes. Rhino-cerebral
      and pulmonary manifestations predominate on account of the airborn spread of the
      spores. Gastro-intestinal, cutaneous and disseminated disease is less common. The
      principal risk factors are immuno-suppression and diabetic keto-acidosis. CASE
      REPORTS: One case of fatal pulmonary mucormycosis and two cases of colonisation
      illustrate both the extreme severity of this disease and the diagnostic
      difficulties facing the physician. The ubiquitous nature of the organism leads to
      frequent colonisation and, moreover, the symptomatology readily mimics that of
      invasive pulmonary aspergillosis. The diagnosis of mucormycosis can only be
      confirmed by pathological and mycological examination of biopsy specimens. These
      requirements conflict with the need for urgent treatment with surgical
      debridement, amphotericin B and control of the underlying pathology. Sadly the
      mortality remains very high, between 50 and 80% in published series. CONCLUSION:
      Currently there is hope of new therapeutic approaches with posaconozole but the
      ineffectiveness of voriconozole and the echinocandines, used more and more
      against aspergillus, raises the possibility of an increase in mucormycosis by
      selection.

PMID- 17519814
TI  - [Pneumothorax following recreational inhalation of nitrous oxide].
AB  - CASE REPORT: A 21 year old man was admitted to hospital as an emergency
      complaining of left sided chest pain. Chest radiograph revealed a complete non
      compressive left-sided pneumothorax which resolved following thoracic drainage. A
      more detailed history revealed repeated and regular use of nitrous oxide by
      inhalation, for its consciousness-altering effect during rave parties.
      DISCUSSION: The principal side effects occurring as a consequence of repeated
      exposures to nitrous oxide are haematological, neuropsychiatric and teratogenic.
      Rare cases of pneumothorax have been described associated with the use of nitrous
      oxide occurring as complications of anaesthesia or during laparoscopy where gas
      diffuses from the abdominal to the pleural cavity. Illicit use of nitrous oxide
      is rare and usually occurs in medical workers. Its spreading to the public may
      lead to accidents and unanticipated side effects. CONCLUSION: Inhaled nitrous
      oxide can reveal asymptomatic pneumothorax by worsening it. The consequences can
      be dramatic in case of illicit use because of ignorance of side effects.

PMID- 17519815
TI  - [Paradoxical lymphadenopathy following treatment of pulmonary tuberculosis. A
      rare condition with controversial management].
AB  - INTRODUCTION: The appearance of a peripheral lymph node tuberculosis in end of
      anti-tuberculosis treatment of a pulmonary tuberculosis is a rare phenomenon
      whose assumption of responsibility, particularly therapeutic, is not reproduced
      on the recommendations of WHO. CLINICAL CASE: It is about a case of a 36 years
      old patient who presented, in end anti-TB treatment for ulceroinfiltrative
      pulmonary tuberculosis, a left axillary adenopathy of important size. The
      treatment consisted with a puncture aspiration with the fine needle as well as
      the prolongation of the duration of the anti-TB treatment from 6 to 9 months. The
      evolution was favourable on radio-clinical and bacteriological level. CONCLUSION:
      The puncture-aspiration of a paradoxical adenopathy in end of the anti-TB
      treatment as well as the prolongation of the duration of the treatment is
      effective and could constitute an alternative to the surgical excision.

PMID- 17519816
TI  - [Idiopathic pulmonary fibrosis and right-to left shunt by patent foramen ovale].
AB  - INTRODUCTION: The association between idiopathic pulmonary fibrosis and patent
      foramen ovale has rarely been described. OBSERVATION: We report the cases of two
      patients, 72 and 59 years old, who presented with refractory hypoxemia in the
      context of pulmonary fibrosis. The hypoxemia was due to a right-to-left shunt
      through a patent foramen ovale (PFO), diagnosed by transoesophageal contrast
      echocardiography. The closure of the PFO allowed a decrease in the oxygen
      requirement in the first case: from 8 l/min to 3 l/min (PaO2 80 mmHg), and in the
      second case oxygen therapy could be stopped (PaO2 76 mmHg on room air). Right-to
      left shunts by PFO are usually associated with pulmonary arterial hypertension
      (systolic pulmonary arterial pressure at 70 mmHg for case 1), but in some cases
      the pulmonary artery pressure is normal (case 2), the shunt being due to an
      anatomical conformation. CONCLUSION: These two cases underline the importance of
      diagnosing right-to-left shunts in patients who have pulmonary fibrosis with
      severe hypoxemia, in order to reduce their oxygen needs.

PMID- 17519817
TI  - [Severe cutaneous toxicity after Pemetrexed as second line treatment for a
      refractory non small cell lung cancer].
AB  - INTRODUCTION: Pemetrexed is a chemotherapeutic drug with good tolerance, used as
      first line treatment for malignant pleural mesothelioma in association with
      cisplatin, and alone as second line treatment in resistant or relapsing non-small
      cell lung cancer (NSCLC). However, cutaneous toxicity has been described,
      principally as a rash. Cutaneous toxicity of all grades has been observed in up
      to 14%, and grade 3 or 4 toxicity in 0.8-1.3% of cases. CASE REPORT: We report
      the case of an 85 year old man treated for NSCLC presenting 15 days after
      administration of the second cycle of pemetrexed with cutaneous lesions including
      erythema, bullae, and desquamation, associated with deterioration in his general
      condition; a skin reaction corresponding to Lyell's syndrome. Treatment with
      steroids and gammaglobulins led to local resolution and improvement in his
      general condition. CONCLUSION: Cutaneous toxicity from pemetrexed should be
      recognised on account of its potential severity. The appearance of skin lesions
      is an indication for careful follow-up for evidence of Lyell's syndrome for which
      intensive management is needed.

PMID- 17519818
TI  - [Acute respiratory distress syndrome complicating Ebstein-Barr virus pneumonia].
AB  - INTRODUCTION: In the immuno-competent adult Ebstein-Barr virus (EBV) infection is
      a self-limiting disease that resolves spontaneously. CASE REPORT: We report a
      case of acute respiratory distress syndrome (ARDS) complicating severe EBV
      pneumonia and requiring prolonged artificial ventilation. The diagnosis was
      confirmed by specific serology and estimation of the viral load by PCR. Apart
      from supportive treatment with artificial ventilation the medical treatment
      included the use of Acyclovir and polyclonal immunoglobulins in the early phase
      and corticosteroids in the late phase. Recovery was progressive and complete.
      CONCLUSION: ARDS can complicate EBV pneumonia in an immuno-competent subject. Its
      management represents a diagnostic and therapeutic challenge.

PMID- 17519819
TI  - [IFCT-0302 trial: randomised study comparing two follow-up schedules in
      completely resected non-small cell lung cancer].
AB  - BACKGROUND: The authorities advocate a minimalist attitude towards the follow-up
      of resected bronchial carcinoma (clinical examination and chest x-ray). A survey
      showed that 70% of French respiratory physicians have chosen to use the CT
      scanner and often endoscopy. The published data are equivocal and are often based
      on retrospective studies. Lung cancer is a good model for a study of post
      operative surveillance. Recurrences often occur in easily observed areas, they
      may be detected while still asymptomatic and are sometimes potentially curable.
      Second primary tumours may develop at the same site. METHODS: The Intergroupe
      Francophone de Cancerologie Thoracique (IFCT) has initiated a trial comparing
      simple follow-up (clinical examination, chest x-ray) with a more intensive follow
      up (CT scan, fibreoptic bronchoscopy). The surveillance will take place every 6
      months for 2 years and then annually until 5 years. EXPECTED RESULTS: The main
      aim is to determine whether intensive follow-up improves patient survival. The
      opposite question is equally important. If an expensive and demanding follow-up
      does not affect the chances of cure these results will influence our practice.

PMID- 17519820
TI  - [Randomised phase II study evaluating oral combination chemotherapy (CCNU,
      cyclophosphamide, etoposide) and intravenous chemotherapy as second-line
      treatment for relapsed small cell bronchial carcinoma (Trial GFPC0501)].
AB  - BACKGROUND: There is no standard second-line treatment for small cell lung cancer
      (SCLC). The prognosis of these patients is poor and special attention should be
      paid to both quality of life and economic factors. METHODS: The aim of this phase
      II randomised trial (GFPC0501) is to compare, in patients with progressive SCLC
      after first-line platinum based chemotherapy, oral multi drug chemotherapy (CCNU,
      cyclophosphamide, etoposide) and classical intravenous chemotherapy with
      cyclophosphamide, doxorubicin and vincristine (CAV) in terms of tolerability,
      efficacy (response rate, median one year survival and overall survival), quality
      of life and consumption of health care resources. Based on a two-stage Bryant and
      Day approach, this study will require a total of 138 patients with an interim
      analysis of the first 38. EXPECTED RESULTS: This trial will provide information
      on several aspects of second-line chemotherapy for patients with SCLC. Thirty six
      patients have been enrolled in 16 centres by December 2006 and the results of the
      interim analysis will be available in June 2007.

PMID- 17519821
TI  - [Perspectives on allergic bronchopulmonary aspergillosis].

PMID- 17519822
TI  - [Smoking cessation in adolescence. Questionnaire study of 248 students].

PMID- 17519824
TI  - [Central apnea].

PMID- 17519825
TI  - [Non-apneic sleep-disordered breathing].

PMID- 17519826
TI  - [Obstructive sleep apnea syndrome].

PMID- 17519829
TI  - The genetics of nonalcoholic fatty liver disease.
AB  - The increasing prevalence of obesity in Western countries has led to a
      significant increase of nonalcoholic fatty liver disease (NAFLD) over the past
      decades. Being part of the metabolic syndrome, NAFLD is thought to be the most
      frequent cause of elevated liver enzymes in the United States affecting up to one
      third of the population. NAFLD is also proposed to be the major cause for
      cryptogenic cirrhosis and hepatocellular cancer of unknown etiology, and thus,
      represents one of the most important problems for hepatologists in the future.
      However, the natural course of NAFLD is highly variable and is influenced by both
      environmental and genetic factors. Polymorphisms in specific genes have been
      proposed to increase the risk of fibrosis in patients with NAFLD. The present
      review article summarizes currently available data from genotype-phenotype
      studies and defines candidate genes that deserve future investigation.

PMID- 17519830
TI  - Bouveret's syndrome. Narrative review.
AB  - Obstruction at the level of the gastric outlet by a gallstone is defined as
      Bouveret's syndrome. It is an uncommon form of gallstone ileus. A single
      gallstone of at least 2.5 cm in diameter is the most common underlying cause of
      Bouveret's syndrome. Diagnosis is based on the clinical manifestations, existence
      of pneumobilia, visualization of lithiasis and demonstration of duodenal
      obstruction. Enterotomy or gastrotomy with or without cholecystectomy and fistula
      repair is the most common surgical therapy. It has high success rate, with
      acceptable surgical morbidity and mortality. Heightened awareness of this
      syndrome may lead to decreased morbidity and mortality.

PMID- 17519831
TI  - What is the reason of elevated alanine aminotransferase level in HBeAg negative
      patients with low viremia: NAFLD or chronic hepatitis?
AB  - BACKGROUND AND STUDY AIMS: Increased alanine aminotransferase (ALT) levels with
      negative hepatitis B virus (HBV) DNA by hybridization is a common problem in
      Turkey where is a mild endemic region. We aimed to evaluate the causes of
      elevated ALT levels in patients who are negative for hepatitis B e antigen
      (HBeAg) and HBV DNA (by hybridization) for at least 6 months. PATIENTS-METHODS:
      Forty-nine patients were enrolled in this study. Histological changes
      [histological activity index (HAI), and the extent of fibrosis] were assessed
      according to the Knodell scoring system and steatosis were graded by Brunt's
      classification for NAFLD in all patients. RESULTS: A mean age of the patients was
      34.9 +/- 12.1 years (16-70). 43 (87.8%) of them were male. Mean ALT level was 95
      +/- 39.7 IU/L (50- 258). Hyperglycemia (>100 mg/dL) and hyperlipidemia were found
      in 12 and 24 patients, respectively. Hepatic steatosis (7 patients grade 1; 5
      patients grade 2; and 7 patients grade 3), ground-glass hepatocyte, chronic
      hepatitis, and Wilson disease were found in liver biopsy in 38.8%, 32.6%, 26.6%,
      2%, respectively. Mean HAI was 6.5 +/- 3.6 (4-12) in chronic hepatitis. Seven
      patients (53.9%) were in stage 1 and 2 while 6 patients (46.1%) were in stage 3
      and 4. CONCLUSIONS: Nonalcoholic fatty liver disease is the most common cause of
      elevated ALT levels in HBeAg negative/HBV DNA negative patients. Chronic
      hepatitis B was found in 26.6% of these patients.

PMID- 17519832
TI  - Anterior pituitary hormone effects on hepatic functions in infants with
      congenital hypopituitarism.
AB  - BACKGROUND: Congenital hypopituitarism is an uncommon cause of neonatal
      cholestasis. Little is known about the effect of anterior pituitary hormone on
      hepatic functions. METHODS: A retrospective review of the medical charts of eight
      infants with congenital hypopituitarism and neonatal cholestasis was performed.
      The results of endocrinological investigations, eye examinations, and magnetic
      resonance imaging were used to classify these infants. RESULTS: Eight infants (4
      male and 4 female; mean age, 1.7 weeks) who presented with cholestatic jaundice
      subsequently (mean age, 7.6 weeks) developed isolated or multiple anterior
      pituitary hormone deficiencies. Persistent hypoglycemia, ocular abnormalities,
      and microphallus were often clinical signs prompting further endocrinological and
      radiological investigations. Septo-optic dysplasia was prevalent, occurring in
      five cases. Cholestasis and hepatosplenomegaly resolved within a mean of 9.7 and
      10 weeks, respectively, in the majority of cases after replacement of
      glucocorticoid and thyroid hormones. However, transaminase levels remained high
      after hormone replacement. Cortisol deficiency and hypoglycemia were noted in all
      cases, often following stress. Hyperlipidemia persisted in one case after the
      resolution of cholestasis and after corticosteroid and thyroid hormone
      replacement therapy. Growth hormone deficiency was not corrected due to the
      absence of hypoglycemia after corticosteroid hormone, an infant's age, and/or a
      lack of financial resources. CONCLUSIONS: In our series, it appears that
      glucocorticoid and thyroid hormones play a significant role in the resolution of
      cholestasis and hepatosplenomegaly. A persistently elevated transaminase level
      and hyperlipidemia after corticosteroid and thyroid hormone replacement may
      indicate the need for long-term follow-up and/or growth hormone therapy.

PMID- 17519833
TI  - Does autonomic dysfunction in cirrhosis liver influence variceal bleed?
AB  - BACKGROUND: Autonomic dysfunction has been documented in cirrhosis liver. Its
      influence on variceal bleed is not known. AIM: To determine the autonomic
      function amongst variceal bleeders in cirrhosis of the liver. MATERIALS AND
      METHODS: Fifty cirrhotics (variceal bleeders: 34) belonging to either sex, Childs
      B, age more than 15 years and non diabetic constituted the study group.
      Parasympathetic function tests included valsalva ratio (E:I ratio) and deep
      breathing test. (Max.-Min. heart rate); sympathetic function included postural
      fall of B.P and a rise in diastolic B.P. with sustained hand grip. A cirrhotic
      was considered to have 'True' autonomic dysfunction when both parasympathetic and
      one of the two sympathetic tests were abnormal. RESULTS: The mean age for men was
      39.64 + 10.6 yrs and for women 39.54 + 15.8 yrs. The male female ratio was 3.5:1.
      Only 10 of the 50 patients (all bleeders) had 'true' autonomic dysfunction i.e.
      20%. Parasympathetic dysfunction alone was positive in 19 (38%) and sympathetic
      in 10 patients (20%). The E:I ratio (p < 0.001) and an increase in diastolic B.P.
      during sustained hand grip (p < 0.04) were significantly positive amongst
      variceal bleeders. CONCLUSION: 'True' autonomic dysfunction can predispose a
      cirrhotic to variceal bleed.

PMID- 17519834
TI  - Predicted binding affinity of candidate HDV epitope: a bioinformatics study.
AB  - Hepatitis D virus (HDV) is an RNA virus that can cause hepatitis. Development and
      approval of new vaccines are the hope for control of the possible emerging
      pandemic of this infection. Recently, the possible epitope as 174 to 195 of HDAg
      was mentioned. Here, the author reports the preliminary data from the
      computational analysis to find binding affinity of the candidate HDV epitope
      using new bioinformatics technique. For LHDAg, the binding affinity for A0203,
      A0301, A1101, A6801 and DRB0101 are acceptable. For S-HDAg, the binding affinity
      for A0203, A0301, A1101, A6801 and DRB6802 are acceptable. The binding affinity
      for A0203 is the most for both L-HDAg and S-HDAg.

PMID- 17519835
TI  - In vitro study on the mechanisms of action of a novel phytotherapeutic compound
      against human hepatoma cells.
AB  - HepG2 human hepatoma cells were incubated for 24 or 48 h with various
      concentrations of YHK solution. After 24 h incubation, cell proliferation and
      cytotoxicity were determined by 3-(4,5-dimethylthiazol-2- yl)-5-(3-
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium (MTT) assay. Cytotoxicity
      or necrosis was expressed as lactate dehydrogenase (LDH) release. After
      exponential growth phase HepG2 cells were treated with different doses of YHK and
      apoptosis was assessed by using an Annexin V-FITC kit. Further, oxidative stress
      was measured by dichlorofluorescein-diacetate (DCFH-DA) assay. As compared to
      control, YHK-treated cultures showed a significant time-course decrease of the
      proliferation rate of HepG2 cell growth (p < 0.01). This is likely to be due to
      an enhanced cytotoxicity (MTT and LDH tests) (p < 0.001). On the other hand, YHK
      showed in vitro to significantly enhance the oxidative stress of HepG2 cell (p <
      0.01) while also markedly increasing apoptosis at 72 h with cells G2/M phase
      arrest (p < 0.01). These data suggest that YHK seem to modulate the extrinsic and
      intrinsic regulators of apoptosis and sensitize tumour cells to apoptosis. These
      preliminary data are worth interest when considering that this nutraceutical has
      been shown in vitro and in vivo to exert protective anti-tumour effect by redox
      statusmodulating and immuno-regulatory actions. Given its lack of toxicity so far
      reported, such natural product might represent an effective nutritional
      supplement in a number of pathological conditions where a chemopreventive
      strategy is planned.

PMID- 17519836
TI  - A Brazilian species of Entamoeba dispar (ADO) produces amoebic liver abscess in
      hamsters.

PMID- 17519837
TI  - Nitrofurantoin-induced lung- and hepatotoxicity.
AB  - We present the case of a patient referred to the gastroenterology service for
      investigation of abnormal liver function tests. She had been taking
      nitrofurantoin for 16 months as prophylaxis against urinary tract infections. CT
      scan showed evidence of lung pneumonitis and low attenuation in the liver
      parenchyma. Nitrofurantoin-induced pneumonitis and hepatotoxicity was diagnosed.
      The patient responded both clinically and biochemically to withdrawal of
      nitrofurantoin. This combination of adverse reaction to nitrofurantoin is rare.

PMID- 17519838
TI  - Hepatocellular carcinoma in patients with autoimmune liver diseases: two case
      reports and literature review.
AB  - BACKGROUND AND AIMS: Hepatocellular carcinoma has been reported as a rare
      complication of autoimmune liver diseases. We describe herein two patients with
      this neoplasia associated with autoimmune hepatitis and primary biliary
      cirrhosis, and we also review the literature. CASES REPORT: The first case
      corresponds to a 49-year-old woman presented for evaluation of right upper
      abdominal pain. She had been diagnosed with autoimmune hepatitis 4 years before.
      Alpha-fetoprotein was markedly elevated and an abdominal MRI showed a 10 cm x 9.0
      cm mass. She received transarterial chemoembolization, and currently the disease
      has progressed to the lungs and bones, and she is on supportive care. The second
      case corresponds to a 68-year-old woman presented for evaluation of a liver mass
      found in a screening ultrasound. She had been diagnosed with primary biliary
      cirrhosis 5 years previously. At admission alpha-fetoprotein was 1000 ng/mL and
      an abdominal MRI revealed a 4 cm x 3 cm liver tumor. She was treated with
      percutaneous radiofrequency ablation getting complete response, and currently she
      has no evidence of neoplastic disease. These two patients constitute the only
      cases of hepatocellular carcinoma associated to autoimmune liver diseases that
      have been attended in our Institute. CONCLUSION: These cases highlight that
      hepatocellular carcinoma secondary to autoimmune hepatitis and primary biliary
      cirrhosis, although rare, can occur in the absence of coexistent viral hepatitis,
      or excessive alcohol consumption. The utility of screening for hepatocellular
      carcinoma in autoimmune liver diseases is still not defined.

PMID- 17519839
TI  - [The gold standard in the treatment of haemorrhoidal disease. Milligan-Morgan
      haemorrhoidectomy vs Longo mucoprolapsectomy: comparing techniques].
AB  - AIM: Although mucosectomy according to Longo was a real revolution in the
      treatment of haemorrhoidal disease, Milligan-Morgan haemorrhoidectomy,
      maintaining the characteristics of a technique which is physiopathologically
      efficacious and easily performed, is still the procedure of choice in some
      clinical conditions. The aim of this study was to evaluate which of the two
      techniques, Milligan-Morgan haemorrhoidectomy and Longo mucoprolapsectomy, could
      be considered the gold standard in the treatment of haemorrhoidal disease.
      METHODS: From March 2002 to October 2006, in the VII Department of General
      Surgery of SUN, we compared two groups of 26 patients each: one treated with
      Milligan-Morgan haemorrhoidectomy, the other one with Longo mucoprolapsectomy.
      Among the patients treated with traditional technique, 16 were suffering from
      grade III haemorrhoids and prolapse, while the other 10 from grade IV
      haemorrhoids and prolapse. The group treated with stapler was composed of 10
      patients affected by grade III haemorrhoids and prolapse, while the other 16 were
      patients complaining for grade IV haemorrhoids and prolapse. For both groups of
      patients the follow-up lasted 12 months; they were controlled at 1 week, 1 month,
      6 months and 1 year after the operation. RESULTS: The level of pain measured with
      a visual analogue scale (VAS) was always higher in the group treated with
      traditional technique. In 69% of the patients treated with stapler and in 59% of
      those treated with open technique there was the first defecation within
      postoperative day 2. The return to normal activity was earlier in patients who
      underwent Longo technique. Among the patients treated with traditional technique,
      7.7% had postoperative bleeding, 15.4% at the 6-month control, suffered from anal
      fissure with associated high pressure of anal sphincter and tenesmus and 7.7%
      showed a recurrence after 1 year. In the group treated with Longo technique,
      11.54% of the patients had a postoperative haemorrhage at the 6-month control,
      7.7% showed substenosis, 3.84% of the patients felt tenesmus; in 3.84% of the
      cases a perianal extra-sphincteric fistula was evident. At 1 year control, 11.54%
      of the patients showed recurrences. CONCLUSION: The conclusion is drawn that it
      does not exist any indication for the Longo technique; however, it seems to give
      the best results in grade III haemorrhoids with prolapse, without sphincteric
      implications.

PMID- 17519840
TI  - [Surgical treatment and prognostic factors in colorectal cancer].
AB  - AIM: The aim of this study was to make a contribution to improve the care of
      patients with colorectal cancer by optimizing times and methods of the follow-up;
      particular attention is given to factors which may be important for the prognosis
      and for the quality of life in the immediate postoperative period. METHODS: The
      study includes all the patients with colorectal cancer who underwent laparotomic
      surgical treatment from 1996 to 2003. The total number of patients was 226 with
      an average age of 65 years; male to female ratio was 1.57:1. According to the
      stage of tumor, an adjuvant radiotherapeutic and/or chemiotherapeutic treatment
      was associated to surgery. RESULTS: On the basis of the preoperative staging and
      tumor localization, our patients underwent: 3 total colectomies, 57 right
      hemicolectomies, 137 left hemicolectomies, 6 Hartmann resections, 19 Miles
      resections, 4 transverse resections. CONCLUSION: The results obtained show that
      the 5-year overall survival is particularly influenced by the stage and the
      factors which directly or indirectly affect the primary tumor; thus the
      prognostic factors which should be considered for the survival and in the follow
      up of these patients are: stage, grading and nodal involvement of the tumor.

PMID- 17519841
TI  - [Diagnosis and treatment of gallbladder and common bile duct stones: our
      experience].
AB  - AIM: The aim of this study was to verify the possibility to identify and treat
      common bile duct (CBD) stones by means of preoperative magnetic resonance
      cholangiopancreatography (MRCP) and endoscopic retrograde
      cholangiopancreatography (ERCP) with a reduction of postoperative complications.
      METHODS: We have carried out a retrospective monocenter analysis of 104
      consecutive patients who underwent a laparoscopic or open cholecystectomy
      performed by a single surgeon at the VII Division of General Surgery, Second
      University of Naples, between 2002 and 2006. Before the operation, we have
      performed highly selective studies like MRCP and ERCP to identify and treat CBD
      stones in patients affected by pancreatitis, jaundice, high liver function tests
      or in case of common bile duct dilation at the US examination, without
      intraoperative cholangiography. RESULTS: Of 104 patients with indication for a
      cholecystectomy, 22 patients (21.2%) presented high levels of cholestasis tests;
      13 patients (12.5%) presented common bile duct dilation at the US examination (>6
      mm diameter). Both groups underwent a MRCP which was positive in 8 patients
      (7.7%), confirming the diagnosis of common bile duct stones. For these reasons we
      removed CBD stones using preoperative ERCP. CONCLUSION: Preoperative ERCP and
      RMCP, without intraoperative cholangiography, is not associated with a
      significant increase in morbility/mortality associated with CBD stones before
      surgical treatment.

PMID- 17519842
TI  - Surgical treatment in postinfarction left ventricular pseudoaneurysm.
AB  - AIM: We evauated the outcome of patients with left ventricular pseudoaneurysms,
      focusing on those treated surgically. METHODS: Between June 1990 and March 2007,
      7 patients underwent surgery because of left ventricular pseudoaneursym following
      myocardial infarction, at our institution. The median time interval between
      myocardial infarction and the diagnosis of left ventricular psedoaneursym was 2.6
      months (range: 15 days to 8 months). The aneursym was resected and the defect was
      closed with a Teflon patch or direct sutures. RESULTS: The location of the
      pseudoaneursym was posterior in 3 patients, inferolateral in 3 patients and
      anterolateral in 1 patient. The aneursym was resected and the defect was closed
      with a Teflon patch in 6 patients. In 1 patient with chronic pseudoaneurysm, the
      defect was closed with direct sutures reinforced with Teflon felt. In addition, 5
      patients underwent coronary artery bypass grafting. The patients have been
      followed-up for a mean period of 45 months (range: 24 to 109 months). CONCLUSION:
      There was no intraoperative death. However, 2 patients died due to multiple organ
      failure, one 17 days and the other 1 month after the surgical operation. There
      was 1 late death due to the cancer. Currently, 1 patient is free of any cardiac
      symptoms, 2 patients have New York Heart Association (NYHA) Class II heart
      failure, and 1 patient with moderate mitral regurgitation is in class III.

PMID- 17519843
TI  - New advances in biology and treatment of gastrointestinal stromal tumours
      (GISTs).
AB  - Gastrointestinal stromal tumours (GISTs) are a precise oncogenetic entity that
      has started the new era of targeted therapies in solid tumours. GISTs are now a
      model to understand the role of oncogenic kinase mutation in tumourigenesis,
      duplication, cell regulation, apoptosis and drug resistance. Ninety-five percent
      of GISTs have some activacting mutation of c-KIT or PDGFRA tyrosine kinase. The
      studies of the last two years have found concrete correlations between mutations
      and anatomical locations of GISTs, prognosis, response to therapy and resistance
      to therapy. Genotyping has increased of importance in the last years as a new
      field for translational researches. The important advances made in molecular
      studies are now a practical tool in diagnosis and therapy of GISTs.

PMID- 17519844
TI  - Metachronous single lung transplantation after contralateral pneumonectomy. A
      ''big'' challenge?
AB  - Single lung transplantation for cystic fibrosis is an uncommon therapy.
      Contralateral pneumonectomy is, in these cases, rarely done before
      transplantation. Herein, we report the case of a single lung transplantation in a
      patient who had previously a contralateral pneumonectomy.

PMID- 17519845
TI  - Laparoscopic treatment of paraesophageal and mixed diaphragmatic hernias. Report
      of two cases.
AB  - Hiatal hernias are classified into 3 types: sliding hernia (type I),
      paraesophageal hernia (type II) and mixed hernia (type III), that is a
      combination of type I and II. The paraesophageal and mixed hernias represent
      about 5-10% of the surgically treated hiatal hernias. The surgical treatment of
      the paraesophageal and mixed hernias is unavoidable because of the high risk of
      severe complications and it has to be considered in a high percentage of cases.
      The most important technical difficulty in the video-laparoscopic treatment is
      represented by the hugeness of the hernial defect and by the challenging
      reduction of the stomach into the abdomen. A cautious dissection of hernial sac
      and diaphragmatic cruses as well as a careful crural repair make the video
      laparoscopic procedure feasible. The operative times are not prolonged and the
      results are similar to the open technique ones. In literature, the incidence of
      both intra and postoperative complications doesn't exhibit statistically
      significant differences between laparoscopic and open techniques. Because of the
      complexity of the laparoscopic procedure, the minimally invasive access has to be
      reserved to surgeons who are well trained in those techniques. In this paper we
      describe 2 cases: one of paraesophageal hernia and the other of mixed hernia
      which were video-laparoscopically treated with the help, in the second case, of a
      Gore-Tex mesh. In both cases the technical results were positive. Intra and
      postoperative complications didn't occur and, one year after the surgical
      procedure, both patients were in good health and recurrence-free.

PMID- 17519846
TI  - Laparoscopic repair of Morgagni hernia and cholecystectomy in a 40-year-old male
      with Down's sindrome. Report of a case.
AB  - Morgagni-Larrey hernia (MH) is an unusual diaphragmatic hernia of the
      retrosternal region. Few cases of MH, treated laparoscopically, associated with
      Down's syndrome (DS) have been reported in literature. On October 2004, a DS 40
      year-old male was admitted to our Department with mild abdominal pain and nausea.
      Hematochemical tests were within the normal range. Ultrasonography showed biliary
      sludge and multiple gallstones. Chest X-ray revealed a right-sided paracardiac
      mass that appeared as MH after a thoraco-abdominal computed tomography (CT). Four
      trocars were placed as a routinary cholecystectomy. Abdominal exploration
      confirmed the presence of a voluminous hernia through a wide diaphragmatic defect
      (12 cm) on the left side of the falciform ligament, containing the last 20 cm
      ileal loops and right colon with the third lateral of transverse. After
      retrograde cholecystectomy and reduction of the herniated ileo-colonic tract from
      multiple adherences, the defect was repaired with an interrupted 2/0 silk suture
      and then a running 2/0 polypropylene suture. Postoperative course was complicated
      by pulmonary edema but subsequently the patient was discharged without further
      complications and has no recurrence after 2 years. In conclusion, surgery is
      necessary for symptomatic MH and to prevent possible severe complications. We
      preferred laparoscopy for the reduced morbidity compared to laparotomy, even if
      in our case the postoperative course was not uneventful. There are still few
      comparative data about the modality of closure of the defect between primary
      repair with nonabsorbable suture material, in case of small defects, or
      continuous monofilament suture or prosthesis in case of large defects.

PMID- 17519847
TI  - Laparoscopic cecopexy for cecal volvulus after laparoscopy. Case report and a
      review of the literature.
AB  - Cecal volvulus is a rare cause of large bowel obstruction. Surgical therapy
      depends on visceral circulatory conditions at diagnosis. Possible options include
      endoscopic decompression, detorsion, cecopexy with or without cecostomy, right
      colectomy with immediate or delayed anastomosis. The present paper describes a
      case of cecal volvulus in a 40-year-old woman after laparoscopic removal of a
      pelvic mass successfully treated by laparoscopic cecopexy.

PMID- 17519848
TI  - Combined endovascular intervention and percutaneous thrombin injection in the
      treatment of iatrogenic pseudoaneurysm. Case report.
AB  - One of the basic techniques of treatment of iatrogenic pseudoaneurysms is
      percutaneous thrombin injection. Unfortunately, success rate of this treatment
      can be limited in cases associated with extensive damage to arterial wall. Our
      paper presents one case of combined treatment involving endovascular occlusion of
      the entry to the false aneurysm and percutaneous thrombin injection into the
      pseudoaneurysm chamber. In our opinion this technique can be successfully applied
      in patients with contraindications for compression therapy, surgical intervention
      or failure of traditional injection due to large entry, multiple arterial wall
      damage or accompanying arteriovenous fistula.

PMID- 17519849
TI  - Delayed presentation of splenic rupture.

PMID- 17519850
TI  - Laboratory assessment of hypercoagulable state. A study in a group of patients
      with venous thromboembolism born in Chioggia.
AB  - AIM: Authors performed a Laboratory assessment for thrombophilia risk factors in
      a group of patients with previous deep venous thrombosis. METHODS: 123
      consecutive patients were considered. The following parameters were investigated
      by using commercially available methods: PT, aPTT, TT, Fibrinogen, D-Dimer, Anti
      thrombin 3 (AT), Protein C (PC), Protein S (PS), activated C protein (APC)
      resistance, Lupus anticoagulant (LA), FV Leiden (G1691a mutation), Prothrombin
      G20210A mutation, MTHFR mutation (G677T mutation), anti Prothrombin auto
      antibodies (PR) IgG and IgM, anti Beta 2 glycoprotein 1 (B2GP1) auto-antibodies
      IgG and IgM, anti Cardiolipin (CL) auto-antibodies IgG and IgM, homocysteine.
      RESULTS: In the 123 patients considered we observed: two AT deficiency, one PC
      deficiencies, one PS deficiency, 60 FV Leiden mutation (six homozygous), 1
      Prothrombin gene mutations (heterozygous), 71 MTHFR mutations (15 homozygous).
      Study of anti phospholipid auto antibodies showed 10 patients positive for LA, 9
      for anti CL antibodies (6IgG and 3IgM), 10 for anti B2GP1 antibody (5 IgG and
      5IgM), 3 for anti PR antibody (IgG). Thirty nine patients showed hyper
      homocysteinemia. CONCLUSION: In our study only 19 patients were free of
      demonstrable thrombophilia risk factor. In 51 subjects a single risk factor was
      identified and in 53 multiple (from 2 to 5) risk factors were identified. In our
      opinion a Laboratory assessment of thrombophilia risk factors after a previous
      episode of deep venous thrombosis is a diagnostic tool of great importance. As a
      matter of fact, in our experience, by using a standard analytical panel, it was
      possible to highlight one or more risk factors in about 85% of the patients
      considered.

PMID- 17519851
TI  - [Hashimoto's thyroiditis and autoimmunity parameters: descriptive study].
AB  - AIM: Aim of the study is a prospective evaluation of the simultaneous presence of
      antinuclear antibodies (ANA) in patients with Hashimoto's thyroiditis as a sign
      of a possible occurrence of another autoimmune disease. METHODS: Thirty two
      patients with Hashimoto's thyroiditis have been selected. No other immunological
      parameters have been used for the selection. All the patients have been submitted
      to ANA research and to thyroid colour-Doppler ultrasonography. Moreover,
      subgroups of patients have been submitted to the research of other autoimmunity
      parameters: 25 patients to AMA (anti-mitochondrial antibodies), ASMA (anti-smooth
      muscle antibodies), ENA (extractable nuclear antigens) and anti-double stranded
      DNA; 7 patients to anti-gastric mucosa; 8 patients to ACA (anti-cardiolipin
      antibodies) IgM and IgG; 12 patients to rheuma-screen. Twenty five patients were
      under L-thyroxine therapy at the time of the samples. RESULTS: Forty-seven
      percent of the patients were ANA positive. Of them 60% showed a title of 1:40.
      The most frequent sonography picture was pseudo-nodular (66%) with predominance
      in ANA negative subgroups (71%) than in ANA positive one (60%). On the basis of
      all the autoimmune parameters evaluated in every subgroups, 72% of our patients
      were positive to at least one autoimmunity parameter and/or have an autoimmune
      disease besides Hashimoto's thyroiditis. CONCLUSION: The conclusion is drawn that
      the patient with Hashimoto's thyroiditis should be considered as an autoimmune
      patient. Thus, it is necessary to carry out an autoimmune screening with ANA in
      every new diagnosed patients and to study in depth the familiar and phatological
      history. Periodical checking of the autoimmune parameters should not be
      underestimated in these patients.

PMID- 17519852
TI  - [Partial androgen deficiency of the aging male and clinical response to
      conventional medical therapy in patients with metabolic syndrome].
AB  - AIM: Analytical study (longitudinal) able to examine the modifications relative
      to some of the main metabolic parameters: body mass index (BMI); waist
      measurement; cholesterol HDL; triglicerydes, medium arterial pressure and some
      insulin sensitivity indicators deduced (index HOMA and index Quicki) in patients
      with full clinical expression of metabolic syndrome (SM) and comparison of the
      results in relation to the condition of testosteronemia. METHODS: Fifty-six male
      patients aged between 52 and 59 years old; 23/56 with full expression of SM,
      assignable (SM) to 3 different groups: group A n=8 (35%) with T normal (>346
      ng/dL); group B n=9 (39%) with values of T at low limits (231-346 ng/dL); group
      C, n=6 (26%) with low values(<231 ng/dL) of T. All patients (SM) were subjected
      to an educational-therapeutic phase of 6 months divided into 3 intervention
      levels: 1) dietotherapy: -20% from the ideal daily caloric needs calculated on
      the base of parameters such as: age, working activity, physical activity
      performed; 2) physical activity: heart rate (HR) included between 40% and 60% of
      the HRmax; three times a week; 3) pharmacological therapy: metmorfin 1 500 mg/die
      and olmesartan 20 mg/die. The condition of hypoandrogenism (group C) was not
      pharmacologically corrected for: a) lack of suitability to the therapeutic scheme
      (2/6); b) presence of controindications absolute and/or relative (4/6).
      Revaluation in 6 months: BMI, waist measurement, serum levels of cholesterol HDL
      and triglicerydes, glycemia, medium arterial pressure, HOMA, Quicki, total
      testosteronemia. RESULTS: Group C (hypoandrogenism) after 6 months shows
      statistically significant differences (Student's T for coupled data), down
      (P<0.05) relative to the following parameters (intragroup comparison): waist
      measurement and serum levels of triglycerides. On the contrary, it doesn't show
      any significant difference regarding: BMI, serum levels of cholesterol HDL, mean
      arterial pressure, HOMA index (found in groups A and B) and Quicki (not found in
      groups A and B). CONCLUSION: The condition of acquired hypoandrogenism of the
      adult serves as an amplifier of an already known condition of dysmetabolism. The
      same condition, when not properly pharmacologically corrected becomes responsible
      for refractoriness to the common pharmacological therapies.

PMID- 17519853
TI  - [Strategies for the development of new tuberculosis vaccines].
AB  - Tuberculosis remains a substantial global health problem causing 2 million
      deaths, and an estimated 8 to 10 million new infections a year. The efficacy of
      the Mycobacterium bovis Bacillus Calmette-Guerin (BCG), the only available
      antituberculosis vaccine, is variable (0-80%), especially in tuberculosis-endemic
      countries. Over the past decade there has been a resurgence of interest in the
      development of new tuberculosis vaccines and some of the most promising are now
      entering into early clinical trials, based on two different strategies. The first
      is to use whole mycobacteria to replace BCG (priming vaccines), either by
      developing a recombinant strain of BCG or an attenuated strain of Mycobacterium
      tuberculosis. To date, two recombinant strains of BCG, one overexpressing antigen
      85B (rBCG-85B) and the other, a urease-deficient BCG mutant which expresses the
      listeriolysin O gene from Listeria monocytogenes (rBCG::DeltaureC-hly+), entered
      into clinical trials. The second approach is to develop subunit vaccines
      (recombinant proteins and viral vectors, and DNA vaccines) expressing
      immunodominant antigen/s from M. tuberculosis able to augmenting BCG protection
      (booster vaccines). At the moment, three major vaccines, namely a recombinant
      modified vaccinia virus Ankara expressing antigen 85A (MVA85A), a fusion protein
      of ESAT6 and 85B (Hybrid 1), and another fusion protein comprising the 32 and 39
      Kda proteins (72f) entered into clinical trials.

PMID- 17519854
TI  - Prevention of human papilloma virus-induced preneoplasia and cancer by
      prophylactic HPV vaccines.
AB  - Persistent infection with human papilloma virus (HPV) is a necessary condition
      for the development of cervical, most of the vulvar and anal carcinoma and their
      precursors. HPV is the most common sexually transmitted virus throughout the
      world. About 70-80% of sexually active people are infected during their lifetime.
      Most infections are transient and asymptomatic and cleared by the host immune
      system within 12-18 months. Only persistent infections predispose to the
      development of genital preneoplasia and cancer. The first vaccine against HPV
      infection has been available in Italy since March 2006. The vaccine is a
      prophylactic, quadrivalent vaccine against the two most common oncogenic HPV
      types 16 and 18, responsible for more than 70% of cervical carcinomas and against
      the two low-risk types 6 and 11 responsible for 90% of cases of genital warts. A
      second, bivalent HPV 16/18 vaccine will be launched soon. The immunogenicity
      (100%) and efficacy of the vaccines is very high (96% against infection, 100%
      against disease). These vaccines constitute a milestone in the battle against
      cervical carcinoma, which is the second most common cancer in young women in
      Europe, with 33,500 new cases diagnosed every year.

PMID- 17519855
TI  - Pneumococcal conjugate vaccines. A review.
AB  - The pneumococcus is currently the most common cause of vaccine-preventable death
      in children aged less than 5 years, and in 2002 was responsible for 716,000
      deaths worldwide. Treatment with antibiotics was the main approach to contain the
      pneumococcus, however, even with effective antibiotics, pneumococcal meningitis
      has a poor prognosis and with the emergence of drug resistant pneumococcal
      disease the need for prevention by vaccine was evident. The first born
      pneumococcal vaccines were polysaccharide vaccines that unfortunately did not
      protect young children. The most vulnerable age group of children, less than 2
      years of age, were without any form of protection from the pneumococcus until the
      licensure of a conjugate vaccine. Conjugation of bacteria polysaccharides to
      carrier proteins has been a significant milestone in the work of vaccine
      development and has been previously used successfully in the production of the
      Haemophilus influenzae-print type b vaccine. The seven-valent pneumococcal
      conjugate vaccine was first licensed in the USA in 2000 and in the European Union
      this conjugate vaccine was licensed in February 2001. Currently, fourteen
      countries have included this vaccine in their immunization programmes.
      Vaccination policies are found to differ greatly across Europe due to differences
      in local epidemiological situation, and also due to economic considerations.
      However, many countries are reviewing their own policies based on available data
      on the burden of pneumococcal disease. This review aims to give an overview about
      the pneumococcus, the development of the pneumococcal conjugate vaccine, and its
      impact.

PMID- 17519856
TI  - Vaccines in development against avian influenza.
AB  - Avian influenza has become a high priority item for all public health
      authorities. An influenza pandemic is believed to be imminent. The only questions
      are what will be the causative agent and when will it happen. Recently, most
      attention has been directed to human cases of avian influenza caused by an H5N1
      avian influenza virus. An effective vaccine will be needed to substantially
      reduce the impact of an influenza pandemic. Despite the fact that the current
      influenza vaccine manufacturing technology is not adequate to support vaccine
      production in the event of a pandemic influenza outbreak, most of the ongoing
      clinical development is occurring with vaccines made in embryonated chicken eggs.
      It is clear that innovative production technology is required. This review
      provides an update on the status of avian vaccine development. In addition
      available manufacturing technologies are presented, some of which could be more
      suitable to adequately respond to an emergency situation where billions of doses
      of vaccines would be required within a very short period of time. The review is
      concluded with some proposed areas of focus for pandemic vaccine preparedness.

PMID- 17519857
TI  - Italy: the first European country to forbid smoking in closed spaces. First
      results.
AB  - Second-hand smoke is a well-known risk factor for several diseases, including
      lung cancer, chronic obstructive pulmonary disease, asthma. Evidence exists that
      smoke-free policies have an effect on reducing or eliminating the exposure to
      second-hand smoke, decreasing the prevalence of smokers, encouraging smokers to
      quit or preventing the initiation of smoking, and reducing cigarettes consumption
      among smokers. Italy has been the first European country to forbid smoking in
      closed places, also in working areas not open to the public, as protection to the
      health of the entire population. This article describes the first results
      obtained from the application of this new law, the positive effects and
      unexpected modifications in the behaviour and social habits of the Italian
      people, thus, revealing itself an important instrument to protect public health.

PMID- 17519858
TI  - Healthcare economics and evidence based medicine: all that glitters is not gold.

PMID- 17519859
TI  - Lymphadenopathy: what we are doing now and what we should be doing.

PMID- 17519861
TI  - [Human papillomavirus vaccination. Consensus Conference in pediatric age].
AB  - Genital human papillomavirus (HPV) infection is the most common sexually
      transmitted infection worldwide. Spontaneous clearance of HPV infection occurs in
      most cases, but chronic infection with high risk genotypes is associated with the
      development of cervical cancer. In particular, HPV 16 and 18 are responsible for
      70% of cancers of the cervix and, in variable proportions, for cancers of the
      vagina, vulva, anus, penis and oropharinx. Low risk HPV genotypes, such as HPV 6
      and 11, cause genital warts. Two prophylactic vaccines using virus like particles
      (VLPs) of L1 capside protein of HPV 16 and 18 have been developed. Of these, one
      also containing VLPs of HPV 6 and 11, has been approved by FDA, EMEA and AIFA for
      use in 9-26 year-old females. Large scale studies have shown that these vaccines
      are safe, well tolerated, elicits high levels of neutralizing antibodies, prevent
      chronic HPV infections due to genotypes present in the vaccine, and associated
      cervical lesions (and genital wars for the quadrivalent vaccine). To be effective
      the vaccines should be given prior to sexual debut. In Italy, the vaccination
      will be offered to 12 year-old girls. This article is the result of a targeted
      Consensus Conference by a panel of experts, which reviews the cornerstones of HPV
      infection, its association with cervical cancer, the advances in prophylactic
      vaccines, and the primary role of the paediatrician for the optimal adoption of
      this new preventive strategy.

PMID- 17519862
TI  - [Predictive ability of a predischarge hour-specific serum bilirubin for
      hyperbilirubinemia in full term infants].
AB  - AIM: The aim of this paper was to assess the ability of total serum bilirubin
      (TSB) levels in the first 3 days of life to predict subsequent nonphysiologic
      hyperbilirubinemia. METHODS: The predictive ability of an hour-specific nomogram
      for TSB values in the first week of life was prospectively assessed in 1496 full
      term neonates admitted to a first level neonatal unit, using a single TSB value
      or two consecutive ones, when available. RESULTS: The incidence of TSB values >
      12 mg/dL was 9.6%, while the incidence of TSB > 15 mg/dL was 2.6%. A sensitivity
      of 97.9% and a negative predictive value (NPV) of 99.6% were obtained with a
      single bilirubin determination applying Trend 12, while 82.5% of sensitivity and
      99.4% of NPV were obtained with Trend 15. Two consecutive TSB determinations
      identified all infants reaching TSB values > 12 mg/dL and all neonates but 5
      reaching TSB values > 15 mg/dL (92.1% of sensitivity and 99% of NPV) CONCLUSION:
      The hour-specific TSB determination in the first 3 days of life is able to
      predict all neonates at risk of nonphysiologic hyperbilirubinemia and could
      facilitate a safe discharge from the hospital and a targeted intervention and
      follow-up.

PMID- 17519863
TI  - [Preadolescents' nutritional habits: a survey in the secondary schools in
      Brianza].
AB  - AIM: This study was aimed at assessing eating habits among preadolescents living
      in Brianza, with a special focus on snacking' and breakfast' habits. METHODS: The
      research was carried out in 12 post-primary schools in Brianza and included 802
      students attending 43 different classes (49.3% males and 50.7% females; mean
      age:12.6 years). The research tool was an ad hoc questionnaire administered to
      the preadolescents attending school on the day of the research. Data were
      analyzed using program Epi Info 6. RESULTS: Many students (78.3%) had breakfast
      in the morning of the questionnaire's administration. Among those perceiving
      themselves as overweight, not having breakfast is more common than among others.
      This information is the opposite of what preadolescents say when inquired about
      their habit to have ''a good breakfast'': only 36.8% of the responders declare
      that it happens on a daily basis. As to snacking, 18.7% of the students declare
      to be used to having multiple snacking during the day; during school recess on
      the day of the survey, 39.9% of respondents declared that they had eaten various
      industrial snacks, while 27.4% had cakes or fresh bread, 1.2% both of them and
      0.6% fruit. On a daily basis, 59.5% report to eat various and different fruits
      and 62.9% report the same when inquired about vegetables. CONCLUSION: Considering
      the importance of a correct nutrition during developmental age and the importance
      of the phase of adolescence in establishing permanent nutritional habits that
      will last life-long, it is thus an educational priority to help preadolescents to
      choose the best foods for their health and well being.

PMID- 17519864
TI  - The role of breastfeeding and passive smoking on the development of severe
      bronchiolitis in infants.
AB  - AIM: Bronchiolitis is an acute infectious disease of the lower respiratory tract
      which causes the obstruction of bronchioles in children younger than 2 years. The
      aim of this study was to investigate the effect of passive smoking alone and in
      conjunction with breastfeeding on the severity of acute bronchiolitis in infancy
      and the duration of hospitalisation. METHODS: We studied 240 consecutive infants
      aged from 6 to 24 months (137 boys and 103 girls) median age 14 months, who
      required hospital admission for acute bronchiolitis at the Paediatric Department
      of Democritus University Hospital, Alexandroupolis, Greece. The outcomes of
      interest were the severity of bronchiolitis and the duration of hospitalisation.
      RESULTS: Among the entire cohort, 122 (50.8%) children presented a severe attack
      of bronchiolitis. In multivariate regression analysis adjusting for confounding
      factors, breastfeeding for less than four months (aOR=6.1, 95% CI=3.4-10.7),
      exposure to environmental tobacco smoke (aOR=2.2, 95% CI=1.1-3.6) and their
      combination (aOR=16.2, 95% CI=6.0-34.3) showed significant association with
      severe bronchiolitis and prolonged hospitalisation. Passive smoking did not
      increase the risk of severe bronchiolitis, when infants breastfed for more than
      four months (aOR=1.9, 95% CI=0.8-5.1). CONCLUSION: In conclusion, exposure to
      environmental tobacco smoke worsens the symptoms and the prognosis of
      bronchiolitis, while breastfeeding seems to have a protective effect even in
      children exposed to environmental tobacco smoke.

PMID- 17519865
TI  - Diagnostic problems and postnatal follow-up in congenital toxoplasmosis.
AB  - AIM: In order to assess the consequences of different clinical approaches in the
      prenatal management of congenital toxoplasmosis, we retrospectively reviewed 58
      pregnant women with Toxoplasma seroconversion and prospectively enrolled their 59
      infants, referred to us from 1999 to 2004. METHODS: Data on clinical, laboratory
      and demographic characteristics of the pregnant women were collected. Their
      children were entered into a 48-month follow-up programme in which clinical,
      instrumental, ophthalmologic and serologic evaluations were carried out at birth,
      at 1, 3, 6, 9, 15, 18, 24, 36 and at 48 months of life. Paediatric treatment with
      Spiramycin alone or alternated with Pyrimethamine-Sulphadiazine was administered
      according to the different clinical cases. RESULTS: Time of infection was dated
      in the first trimester for 24 women (41%), in the second trimester for 18 women
      (31%) and in the third trimester for 16 (28%). In the first trimester of
      pregnancy 20 of the 24 infected women had undergone amniocentesis, while the test
      had not been performed on any of the women infected in the third trimester.
      Serological follow-up revealed that 11 (19%) of the infants had been infected. An
      alternating regimen with Pyrimethamine-Sulphadoxine was administered to the
      infected children. All the infants were clinically asymptomatic, and the
      instrumental follow-up revealed specific toxoplasmosis anomalies in 4/11 infected
      children. CONCLUSION: Our results highlight issues and problems concerning
      current prenatal diagnostic tests and the therapeutic approach based on PCR
      testing of amniotic fluid alone. The incidence of ocular-cerebral lesions
      observed in children born to women with seroconversion in the third trimester
      raises questions about the diagnostic and therapeutic approach for these women
      and their offspring. Paediatric therapeutic protocol, with alternating
      Pyrimethamine-Sulphadiazine regimen, applied also to asymptomatic children born
      to women with inadequate prenatal diagnostic management, could prevent severe
      sequelae.

PMID- 17519866
TI  - Cardiac manifestations of inborn errors of metabolism.
AB  - AIM: The aim of the study was to investigate the frequency and type of cardiac
      manifestations in a defined group of patients with inborn errors of metabolism.
      This paper also explores the key role of cardiac manifestations in the diagnosis
      of inborn errors of metabolism in daily practice. METHODS: Out of the 287
      patients with the potential for inborn errors of metabolism who had been referred
      to the University Hospital of Heraklion (202 children and adolescents and 85
      adults), 41 were found to have a variety of cardiac manifestations, including
      cardiomyopathy, cardiomegaly, atrioventricular conduction disorders and coronary
      artery disease. RESULTS: In 15 out of the 41 patients a diagnosis of inborn
      errors of metabolism was established, while the total number of patients with
      inborn errors of metabolism was 60 out of the 287. In 6 out of the 15 patients
      the major symptoms were from the cardiovascular system and 7 of them were adults
      with symptoms initiating in childhood. CONCLUSION: The cardiac findings consist
      of a neglected area in the diagnosis of the inborn errors of metabolism.
      Neurologists, pediatricians and internists should cooperate with cardiologists in
      managing people with unexplained cardiac symptoms and signs and be aware that
      several inborn errors of metabolism are associated with cardiac abnormalities and
      mild neurologic findings.

PMID- 17519867
TI  - [Pediatric craniopharyngioma: long-term results in 61 cases].
AB  - AIM: The aim of this study was to analyze the long-term results of the surgical
      management of craniopharyngioma in children by reviewing a series of patients
      consecutively treated in a single institution, and to assess the efficacy of
      intratumoral chemotherapy with interferon-alpha. METHODS: Sixty-one paediatric
      patients (38 males and 23 females; mean age: 8 years) have been surgically
      treated in the last 20 years. The goal of surgery was to remove the tumour as
      much as possible. Postoperative radiotherapy was administered only to children
      aged more than 4 year old and with postsurgical evolutive remnant. Three patients
      were treated with intratumoral administration of interferon-alpha. The mean
      follow-up is 8.4 years (median: 7 years). RESULTS: All the 55 surviving patients
      enjoy a normal social life, except for 3 of them (visual and/or neurological
      deficits); endocrine function, compromised in 3/5 of cases, is managed by chronic
      hormone replacement; neuropsychological assessment is satisfactory in almost all
      the cases. Although obesity does not seem to be an important social limit, it
      represents a real management problem. Interferon-a was useful in transitorily
      arresting the growing cystic craniopharyngiomas. CONCLUSION: The current
      experience confirms the still remarkable challenges in the treatment of
      craniopharyngioma in childhood. Surgery should aim not only at removing the
      tumour, but also at preserving the late neuro-endocrinological functions.
      Intracystic chemotherapy with interferon-alpha might represent an effective
      option to postpone the surgical operation until the maturation of the
      hypothalamic-hypophyseal pathway is completed. However, it can not replace the
      traditional surgical management.

PMID- 17519868
TI  - [Cerebral hemodynamics and major surgery].
AB  - AIM: Near infrared spectroscopy (NIRS) is a non invasive optical technique to
      assess the monitoring of oxygenation and cerebral hemodynamics. Aim of our study
      was to value cerebral hemodynamics during major surgery to reduce the period of
      possible modifications of cerebral oxygenation. METHODS: Twenty-five newborns
      which underwent surgical intervention (8 diaphragmatic hernia, 8 esophageal
      atresia, 1 neck lymphangioma, 8 intestinal malformation) were studied during
      surgery by means of NIRS (NIRO 300), using an electrode applied to the scalp in
      the frontoparietal region. We monitored the Tissue Oxygenation Index (TOI) as
      well as the changes in concentration of total haemoglobin (tHb), oxygenated
      haemoglobin (O2Hb) and deoxygenated haemoglobin (HHb). The changes have been
      expressed as difference from the basal value recorded at the beginning of
      surgery. RESULTS: During the surgical intervention O2Hb, tHb and TOI decreased
      (DeltaO2Hb=-11.4+/-6.5 microM; P<0.001; DeltatHb=- 7.54+/-4.3 microM, P<0.05;
      microTOI=-12.5+/-5.5%, P<0.001), and HHb increased (DeltaHHb=+4.80+/-2.30 microM,
      P<0.001); the greatest changes occurred when the viscera were positioned into the
      abdomen (in diaphragmatic hernia and intestinal malformation). CONCLUSION: The
      present study suggests that NIRS, during major surgery, is able to monitor
      oxygenation and cerebral hemodynamics thus allowing a real time evaluation of
      some intraoperative procedure aftereffects that, if timely modified, could reduce
      cerebral hypoxia risks.

PMID- 17519869
TI  - A review on eating disorders and adolescence.
AB  - Eating disorders in adolescence are a public health concern with both personal
      costs and a financial burden for the community health services. This paper is a
      review of incidence and gender differences of eating disorders; comorbid
      psychopathology, including substance abuse, mood disorders, anxiety disorders and
      personality disorders; developmental and intellectual factors; family, socio
      cultural functioning and birth order; self-injury and suicidal behaviour with
      health outcome and therapy success rate. We have also asked several questions
      from our clinical experience and tried to answer them with our clinical knowledge
      and based on literature review. Overall, there is an indication that therapy
      success is significantly correlated with (low) manifestation, specifically for
      social problems and aggressivity. Due to the complexity of factors involved in
      the manifestation of eating disorders, the inclusion of cognitive-behavioural
      therapy as well as family-oriented therapeutic concepts coupled with medical
      treatment would appear to offer an intervention inventory, which would be most
      effective in offering adolescents optimal treatment programmes. The implications
      of our review is discussed in terms of psychotherapeutic treatment plans for
      adolescents in clinical care.

PMID- 17519870
TI  - Update of the medical treatment of West syndrome.
AB  - West syndrome is a generalized epilepsy syndrome composed of infantile spasms and
      onset is usually within the first year of life. Although West syndrome is well
      known clinical epileptic syndrome, there is no agreement about the first- and
      second-line treatments. In the last years a great progress in the development of
      new antiepileptic drugs allow us to have a large choice of treatment options to
      control the seizures. This review outlines the usefulness of the different
      antiepileptic drugs for the treatment of West syndrome.

PMID- 17519871
TI  - [Proposal for a protocol for the staging of incontinentia pigmenti in pediatric
      age].
AB  - Incontinentia Pigmenti (IP) is an X-linked dominant disorder of skin with
      neurologic and ophthalmologic involvement. IP predominantly affects females
      because the mutations are usually lethal in males in utero. IP is characterized
      by abnormalities of neuroectodermal tissues. IP is caused by mutations in a gene
      called NEMO, which is required to activate the NF-kB pathway. We present a
      diagnostic protocol for IP and a meta-analysis of the clinical spectrum of IP in
      82 patients cited by MEDLINE in the European literature from 2000 to 2006.

PMID- 17519872
TI  - [Evaluation of C reactive protein and others immunologic markers in the diagnosis
      of neonatal sepsis].
AB  - Neonatal sepsis occurs from 1 to 21 newborns out of 1 000 live births with
      mortality rates as high as 30% up to 69%. The most important risk factors are
      prematurity, low birth weight, invasive medical procedure and prolonged
      hospitalization in neonatal intensive care units. An aimed and restrictive
      antibiotic therapy has an outstanding importance to reduce both morbidity
      mortality rates and multiple drug-resistance. Generally, preterm newborns present
      nonspecific clinical signs of infection. The use of high sensitivity infection
      markers and a negative predictive value (near 100%) are important to distinguish
      infected and noninfected patients before the culture results and to verify
      adequacy and duration of antibiotic therapy. This article reviews the immunologic
      function and practical use of C reactive protein (CRP) and other markers in the
      diagnosis of neonatal sepsis. While CRP is a specific late infection marker,
      cytokines, cell surface markers and procalcitonin (PCT) are early infection
      markers. The use of multiple markers as CRP, PCT, IL-6, IL-8, CD64, CD11b is
      useful both to early (24-48 h) diagnose of neonatal sepsis, and to monitorate the
      antibiotic treatment while waiting for the results of cultural examinations.

PMID- 17519873
TI  - [Accidental ethyl alcohol intoxication in a 30-day-old infant. Clinical findings
      and neurological follow-up].
AB  - Fetus damages due to alcohol abuse in pregnancy, fetal alcohol syndrome (FAS),
      are widely documented in the literature, whereas short and long term clinical
      signs of acute alcohol intoxication in newborn babies are poorly described. In
      our study we describe the case of a 30-day-old newborn baby erroneously fed with
      70 mL of white wine in place of the water for milk dilution. The baby clinical
      features were torpor, tremors, slight fever without metabolic anomalies typical
      of classic acute alcohol intoxication such as hypoglycemia, hypothermia,
      metabolic acidosis and coma. Periodical follow-up a 2, 3, 6 and 12 months were
      performed in order to evaluate neuromotor development using Bayley Scales of
      Infant Development II, for children between 1 and 42 months old. The results
      showed normal psychomotor development in our patient.

PMID- 17519874
TI  - [Specific learning disabilities and psychopathological aspects: the importance of
      early diagnosis].
AB  - The case of a couple of monozygotic twins, for whom the diagnosis of Specific
      Learning Disabilities was made when they were 14.5 years old, even if reading and
      writing difficulties had been present since the beginning of primary school, is
      described. The consultation had been required due to difficulties in relating
      with same age boys, with social withdrawal and depressive traits, leaving in
      second place school difficulties; clinical suspect has led to extend the
      evaluation to include the neuropsychological aspects and so to reach the
      diagnosis. The differences in terms of adaptive modalities facing the discomfort,
      probably based on temperament differences, and neuropsychological disorder (low
      grade dyslexia for one twin, dis-orthography and low-to-medium grade dyslexia for
      the other one) are discussed. The acquired awareness of being intelligent has
      permitted the boys to look back in a new way to the school failures they had
      collected through years; namely, understanding that their difficulties reflected
      a specific neuropsychological deficit has permitted to reconsider their own past
      history with a consequent modification of the ''beliefs'' about their abilities.
      This all has led as a consequence to an increase of life quality (with an
      improved school and relational adaptation), without cancelling but instead
      supporting the research of on individuality based on temperament differences.
      This was possible in spite of the evident delay in reaching the diagnosis and the
      consequent accumulation of frustration and inadequacy experiences for many years;
      it's therefore demonstrated the importance of a global evaluation of patients
      with anamnesis of difficulties in learning to read and write, also in order to
      treat the possible psychopathological aspects of the clinical picture, which can
      be the result of a sense of helplessness.

PMID- 17519875
TI  - Hirsutism.

PMID- 17519876
TI  - The development of novel agents for the treatment of colorectal cancer: a
      critical review of current practice and some suggestions for the future.
AB  - The pathways to approval of new therapeutic agents in the United States and
      globally rely on the performance of well-designed clinical trials demonstrating
      both safety and efficacy. We recognize that the last decade has seen some great
      successes in improving outcomes for patients with cancer and, specifically, for
      patients with colorectal cancer. The development of novel agents active in colon
      cancer has led to improved survival and cure rates. However, because of the
      number of agents now available and the established practice patterns, it is
      becoming increasingly difficult to test new agents in cancer, particularly in
      colorectal cancer. The focus of this article is to review the current clinical
      trial designs with a critical eye and propose novel approaches to bringing new
      agents into the armamentarium of agents effective against colorectal cancer. Our
      current standards for drug development are increasingly problematic, and it is
      imperative that we develop new expectations and supporting standards in cancer
      drug development.

PMID- 17519877
TI  - Treatment of incidental thromboses in cancer patients.

PMID- 17519878
TI  - Pharmacokinetics and pharmacodynamics in the elderly.

PMID- 17519879
TI  - Advances in the management of AML in the elderly.

PMID- 17519880
TI  - The use of microarray technology in the management of breast cancer.

PMID- 17519881
TI  - Creating an infrastructure for pediatric oncology drug development.

PMID- 17519882
TI  - In focus: non-small cell lung cancer: E1505.

PMID- 17519883
TI  - The 800-lb gorilla we all ignore: treatment of NSCLC in elderly and PS 2
      patients.
AB  - Patients with non-small cell lung cancer,NSCLC, typically have advanced disease
      on presentation. First-line palliative platinum-based doublet chemotherapy has
      emerged as the standard of care in fit, younger patients. However, patients with
      advanced age and/or impaired performance status have been relatively
      underrepresented in clinical trials. Retrospective analyses and the few existing
      prospective randomized trials in these populations have suggested a poorer
      overall prognosis, yet also provide evidence of benefit from systemic therapy.
      Toxicity is generally manageable, and in most cases, comparable to that of
      younger, healthier patients. There are clearly expanding roles for nonplatinum
      chemotherapy agents and newer targeted therapies, which have generally yielded
      decreased toxicity compared to platinum-based chemotherapy without sacrificing
      efficacy. Appropriate pretreatment assessment and proper patient selection is of
      paramount importance; it is imperative to treat patients who are most likely to
      garner benefit. In summary, data suggest that these relatively neglected
      populations of NSCLC patients can be safely treated, and can benefit from
      palliative systemic therapy. Single-agent chemotherapy is generally recommended
      over combination chemotherapy, although investigation of newer targeted therapies
      or alternative agents may allow for combination therapy in the near future.
      Further prospective investigation is absolutely warranted.

PMID- 17519884
TI  - Intravenous azacitidine for MDS.

PMID- 17519887
TI  - Developments in the treatment of lymphoproliferative disorders: rising to the new
      challenges of CLL therapy. A report of a symposium presented during the 48th
      American Society of Hematology Annual Meeting and Exposition, December 8, 2006,
      Orlando, Florida.

PMID- 17519888
TI  - Recent Advances in the Treatment of MDS. A review of selected presentations from
      the 48th Annual Meeting of the American Society of Hematology, December 9-12,
      2006, Orlando, Florida.

PMID- 17519890
TI  - Proteolytic disassembly is a critical determinant for reovirus oncolysis.
AB  - Mammalian ortheoreoviruses are currently being investigated as novel cancer
      therapeutics, but the cellular mechanisms that regulate susceptibility to
      reovirus oncolysis remain poorly understood. In this study, we present evidence
      that virion disassembly is a key determinant of reovirus oncolysis. To penetrate
      cell membranes and initiate infection, the outermost capsid proteins of reovirus
      must be proteolyzed to generate a disassembled particle called an infectious
      subviral particle (ISVP). In fibroblasts, this process is mediated by the
      endo/lysosomal proteases cathepsins B and L. We have analyzed the early events of
      infection in reovirus-susceptible and -resistant cells. We find that, in contrast
      to susceptible glioma cells and Ras-transformed NIH3T3 cells, reovirus-resistant
      cancer cells and untransformed NIH3T3 cells restrict virion uncoating and
      subsequent gene expression. Disassembly-restrictive cells support reovirus
      infection, as in vitro-generated ISVPs establish productive infection, and
      pretreatment with poly(I:C) does not prevent infection in cancer cells. We find
      that the level of active cathepsin B and L is increased in tumors and that
      disassembly-restrictive glioma cells support reovirus oncolysis when grown as a
      tumor in vivo. Together, these results provide a model in which proteolytic
      disassembly of reovirus is a critical determinant of susceptibility to reovirus
      oncolysis.

PMID- 17519891
TI  - Long-term correction of beta-thalassemia with minimal cellular requirement and
      transplantation modalities.
AB  - Determination of minimal criteria, pre-transplantation regimens, and infusion
      modalities for effective and reproducible bone marrow (BM) therapy in beta
      thalassemia is of fundamental importance for clinical application. In this study,
      using repopulation assays, we first established the minimal proportion of normal
      BM stem cells that would result in therapeutic benefit in this red blood cell
      (RBC) disorder. Eight groups of stable chimeric hemizygous beta-thalassemic (hemi
      betathal) mice (10-89%) were systematically subjected to cellular, molecular, and
      patho-physiologic analyses for approximately 2 years. In the chimeric hemi
      betathal groups containing 19-24% normal donor cells, all RBC parameters and
      consequent erythropoiesis were significantly improved. Mice in the 24% chimeric
      group and above had marked reduction in organ pathology including iron deposits,
      and survived to a normal lifespan. Altogether, these results established that a
      range of 19-24% normal BM cells is sufficient for long-term significant
      correction of the hemi-betathal phenotype. We also determined concomitantly the
      minimal myelosuppression radiation doses, the number of cells to be infused, and
      the number of infusions required in order to attain this therapeutic range in
      hemi-betathal mice. Importantly, with prior minimal myelosuppression with 1 or 2
      Gy, and using cell doses of 40 or 60 millions, 100% of the recipients were
      successfully engrafted at therapeutic levels, provided the cells were
      administered in two doses. This study has therefore determined the therapeutic
      chimeric level as 19-24% of normal cells, and has also defined the minimal
      transplantation modalities necessary for the stable and successful correction of
      the hemi-betathal phenotype.

PMID- 17519892
TI  - Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for
      size liver grafts regeneration.
AB  - Ischemia-reperfusion (I/R) associated with small-for-size liver transplantation
      (SFSLT) impairs liver graft regeneration. Mesenchymal stem cells (MSCs) have the
      capability, under specific conditions, of differentiating into hepatocytes.
      Hepatocyte growth factor (HGF) has potent anti-apoptotic and mitogenic effects on
      hepatocytes during liver injury, and has been utilized in many experimental and
      clinical applications. In this study, we implanted HGF-expressing MSCs into liver
      grafts via the portal vein, using a 30% small-for-size rat liver transplantation
      model. HGF, c-met expression, hepatic injury and liver regeneration were assessed
      after liver transplantation. Our study demonstrated that MSCs over-expressing HGF
      prevented liver failure and reduced mortality in rats after SFSLT. These animals
      also exhibited improved liver function and liver weight recovery during the early
      post-transplantation period. Using green fluorescent protein (GFP) gene as a
      marker, we demonstrated that the engrafted cells and their progeny incorporated
      into remnant livers and produced albumin. These findings suggest that MSCs
      genetically modified to over-express HGF and implanted in the liver graft, may
      offer a novel approach to promoting liver regeneration after small-for-size
      transplantations.

PMID- 17519893
TI  - Correction of clinical manifestations of canine mucopolysaccharidosis I with
      neonatal retroviral vector gene therapy.
AB  - Mucopolysaccharidosis I (MPS I) (Hurler syndrome) is due to deficient alpha-L
      iduronidase (IDUA) activity and is the most common of the MPS disorders. Neonatal
      MPS I dogs were injected intravenously (IV) with a gamma retroviral vector
      containing a complete long-terminal repeat (LTR) and an internal human alpha(1)
      antitrypsin (hAAT) promoter upstream of the canine IDUA complementary DNA (cDNA).
      This resulted in stable serum IDUA activity of 366 +/- 344 units (U)/ml (28-fold
      normal) for up to 1.8 years, which likely derived primarily from secretion of
      IDUA by transduced liver cells. Retroviral vector (RV)-treated dogs had >18% of
      normal IDUA activity in organs and had decreased severity and/or incidence of
      hernias, chest deformities, joint disease, facial dysmorphia, corneal clouding,
      valvular heart disease, and aortic dilatation as compared with untreated MPS I
      dogs. The marked reduction that was observed in lysosomal storage in the brain of
      RV-treated dogs may have been due in part to expression from the LTR of the
      vector in cells in the brain. This possibility will be explored in future
      studies, because the potential for insertional mutagenesis has raised concerns
      about using vectors with an intact LTR. If proven safe, this gene therapy
      technique may be utilized in treating children with Hurler syndrome.

PMID- 17519894
TI  - Mesenchymal stem cell-mediated gene delivery of bone morphogenetic protein-2 in
      an articular fracture model.
AB  - In articular fractures, both bone and cartilage are injured. We tested whether
      stem cells transduced with bone morphogenetic protein 2 (BMP2) can promote bone
      and cartilage repair. Distal femoral articular osteotomies in nude rats were
      treated with stem cells, either wild-type or transduced with an adenoviral (Ad)
      BMP2. Cells were delivered in alginate (ALG) carrier or by direct injection in
      saline solution. Gene expression of these cells at the osteotomy site was
      confirmed by in vivo imaging. At day 14, only the group that received AdBMP2 stem
      cells by direct injection showed completely healed osteotomies, while other
      groups remained unhealed (P < 0.0003). In ALG groups, bone healing was impeded by
      the development of a chondroid mass, most pronounced in the AdBMP2 ALG group (P <
      0.002). We were successful in achieving repair of both bone and cartilage in
      vivousing direct stem cell injection. Our data suggests that BMP2 augmentation
      might be critically important in achieving this effect.

PMID- 17519895
TI  - Blood pressure and renal cancer risk: the HUNT Study in Norway.
AB  - In a prospective study of 36,728 women and 35,688 men during 18 years of follow
      up, compared to systolic pressure <130 mm Hg, levels of 130-149, 150-169 and
      >or=170 mm Hg in women were associated with relative risks of renal cell cancer
      of 1.7, 2.0 and 2.0, respectively (P for linear trend, 0.11). In men, there was
      no association with blood pressure.

PMID- 17519896
TI  - Lifestyle and socio-demographic factors associated with high-risk HPV infection
      in UK women.
AB  - The world age-standardised prevalence of high-risk HPV (hrHPV) infection among
      5038 UK women aged 20-59 years, with a low-grade smear during 1999-2002, assessed
      for eligibility for TOMBOLA (Trial Of Management of Borderline and Other Low
      grade Abnormal smears) was 34.2%. High-risk HPV prevalence decreased with
      increasing age, from 61% at ages 20-24 years to 14-15% in those over 50 years.
      The age-standardised prevalence was 15.1, 30.7 and 52.7%, respectively, in women
      with a current normal, borderline nuclear abnormalities (BNA) and mild smear. In
      overall multivariate analyses, tertiary education, previous pregnancy and
      childbirth were associated with reduced hrHPV infection risk. Risk of infection
      was increased in non-white women, women not married/cohabiting, hormonal
      contraceptives users and current smokers. In stratified analyses, current smear
      status and age remained associated with hrHPV infection. Data of this type are
      relevant to the debate on human papillomavirus (HPV) testing in screening and
      development of HPV vaccination programmes.

PMID- 17519897
TI  - Differential expression of DHHC9 in microsatellite stable and instable human
      colorectal cancer subgroups.
AB  - Microarray analysis on pooled samples has previously identified ZDHHC9 (DHHC9) to
      be upregulated in colon adenocarcinoma compared to normal colon mucosa. Analyses
      of 168 samples from proximal and distal adenocarcinomas using U133plus2.0
      microarrays validated these findings, showing a significant two-fold (log 2)
      upregulation of DHHC9 transcript (P<10(-6)). The upregulation was more striking
      in microsatellite stable (MSS), than in microsatellite instable (MSI), tumours.
      Genes known to interact with DHHC9 as H-Ras or N-Ras did not show expression
      differences between MSS and MSI. Immunohistochemical analysis was performed on 60
      colon adenocarcinomas, previously analysed on microarrays, as well as on tissue
      microarrays with 40 stage I-IV tumours and 46 tumours from different organ sites.
      DHHC9 protein was strongly expressed in MSS compared to MSI tumours, readily
      detectable in premalignant lesions, compared to the rare expression seen in
      normal mucosa. DHHC9 was specific for tumours of the gastrointestinal tract and
      localised to the Golgi apparatus, in vitro and in vivo. Overexpression of DHHC9
      decreased the proliferation of SW480 and CaCo2 MSS cell lines significantly. In
      conclusion, DHHC9 is a gastrointestinal-related protein highly expressed in MSS
      colon tumours. The palmitoyl transferase activity, modifying N-Ras and H-Ras,
      suggests DHHC9 as a target for anticancer drug design.

PMID- 17519898
TI  - Increased chromosomal stability in cultures of ovarian tumours of low malignant
      potential compared to cystadenomas.
AB  - Cell cultures of ovarian cystadenomas transfected with SV40 large T antigen are
      not immortal because they invariably reach a phenomenon called crisis, which is
      triggered in part by telomere attrition. Recovery from crisis may be an integral
      component of the malignant transformation process. We reported earlier that such
      ovarian cystadenoma cell cultures undergo severe changes in DNA ploidy as they
      approach crisis and that such changes are an important determinant of crisis
      independent of telomere attrition. Here, we show that in sharp contrast to these
      benign ovarian tumours, the DNA content of ovarian tumours of low malignant
      potential (LMP) was remarkably stable as they approached crisis, suggesting that
      telomere attrition was the main determinant of this mortality checkpoint. Lack of
      a ploidy-based crisis was not due to loss of expression of a functional SV40
      large T antigen protein. We conclude that ovarian LMP tumours are characterised
      by increased numerical chromosomal stability compared to cystadenomas. This might
      account for the fact that most LMP tumours are diploid or near diploid in vivo.
      This fundamental difference in chromosomal stability between ovarian cystadenomas
      and LMP tumours also suggests potential differences in predisposition to
      progression to malignancy between these two ovarian tumour subtypes.

PMID- 17519899
TI  - Further observations on the relationship between the FGFR4 Gly388Arg polymorphism
      and lung cancer prognosis.
AB  - The Gly388Arg polymorphism in the fibroblast growth factor receptor 4 (FGFR4)
      gene has been reported to influence prognosis in a wide variety of cancer types.
      To determine whether Gly388Arg is a marker for lung cancer prognosis, we
      genotyped 619 lung cancer patients with incident disease and examined the
      relationship between genotype and overall survival. While we employed a
      comprehensive set of statistical tests, including those sensitive to the
      detection of differences in early survival, our data provide little evidence to
      support the tenet that the FGFR4 Gly388Arg polymorphism is a clinically useful
      marker for lung cancer prognosis.

PMID- 17519901
TI  - Adenovirus-mediated hypoxia-targeting cytosine deaminase gene therapy enhances
      radiotherapy in tumour xenografts.
AB  - Hypoxia is closely associated with the radioresistance of tumours; therefore,
      targeting hypoxic areas is very important for cancer therapy. The aim of this
      study is to establish such a targeting strategy by applying a bacterial cytosine
      deaminase (BCD)/5-fluorocytosine (5-FC) gene therapy system and to examine
      whether the strategy enhances the efficacy of radiotherapy in a tumour xenograft.
      The hypoxia-responsive promoter 5HREp, in which five copies of the hypoxia
      response element (HRE) enhance transcription from a cytomegalovirus minimal
      promoter, was employed to induce the expression of BCD under hypoxic conditions.
      The adenoviral vector Ad/5HREp-BCD, encoding the gene 5HREp-BCD, robustly induced
      BCD expression under hypoxic conditions and this led to significant cytotoxicity
      in combination with 5-FC in vitro. Intratumoral Ad/5HREp-BCD administration
      resulted in the expression of BCD at the border between normoxic and necrotic
      regions. The BCD/5-FC gene therapy enhanced the therapeutic effects of both
      single (12.5 Gy) and fractionated (3 Gy x 5 days) radiotherapy with few side
      effects and significantly increased tumour growth doubling time by up to 2.4-fold
      (P<0.01) and 2.5-fold (P<0.05), respectively. All of these results suggest that
      the present BCD/5-FC gene therapy has the ability to specifically target hypoxic
      tumour cells and significantly improves the control of tumour growth after
      radiotherapy.

PMID- 17519900
TI  - Mechanisms of adverse effects of anti-VEGF therapy for cancer.
AB  - Advances in understanding the role of vascular endothelial growth factor (VEGF)
      in normal physiology are giving insight into the basis of adverse effects
      attributed to the use of VEGF inhibitors in clinical oncology. These effects are
      typically downstream consequences of suppression of cellular signalling pathways
      important in the regulation and maintenance of the microvasculature.
      Downregulation of these pathways in normal organs can lead to vascular
      disturbances and even regression of blood vessels, which could be intensified by
      concurrent pathological conditions. These changes are generally manageable and
      pose less risk than the tumours being treated, but they highlight the properties
      shared by tumour vessels and the vasculature of normal organs.

PMID- 17519902
TI  - Transmucosal fentanyl vs intravenous morphine in doses proportional to basal
      opioid regimen for episodic-breakthrough pain.
AB  - The use of supplemental doses of opioids is commonly suggested to manage
      breakthrough pain. A comparative study of intravenous morphine (IV-MO) and oral
      transmucosal fentanyl citrate (OTFC) given in doses proportional to the basal
      opioid regimen was performed in 25 cancer patients receiving stable opioid doses.
      For each episode, when it occurred and 15 and 30 min after the treatment, pain
      intensity and opioid-related symptoms were recorded. Fifty-three couples of
      breakthrough events, each treated with IV-MO and OTFC, were recorded. In episodes
      treated with IV-MO, pain intensity decreased from a mean of 6.9 to 3.3 and to 1.7
      at T1 and T2, respectively. In episodes treated with OTFC, pain intensity
      decreased from a mean of 6.9 to 4.1 and to 2.4 at T1 and T2, respectively.
      Statistical differences between the two treatments were found at T1 (P=0.013),
      but not at T2 (P=0.059). Adverse effects were comparable and were not
      significantly related with the IV-MO and OTFC doses. Intravenous morphine and
      OTFC in doses proportional to the scheduled daily dose of opioids were both safe
      and effective, IV-MO having a shorter onset than OTFC. Future comparative studies
      with appropriate design should compare titration methods and proportional methods
      of OTFC dosing.

PMID- 17519903
TI  - Desmosomes: a role in cancer?
AB  - Much evidence now attests to the importance of desmosomes and their constituents
      in cancer. Alterations in the expression of desmosomal components could
      contribute to the progression of the disease by modifying intracellular signal
      transduction pathways and/or by causing reduced cell adhesion. The Wnt/beta
      catenin pathway is a potential target because of the involvement of the
      cytoplasmic desmosomal protein plakoglobin. Loss of desmosomal adhesion is a
      prerequisite for the epithelial-mesenchymal transition, implicated in the
      conversion of early stage tumours to invasive cancers.

PMID- 17519904
TI  - Compartmentalisation of EGFR signalling might potentiate the optimal use of EGFR
      tyrosine kinase inhibitors in cancer therapeutics.

PMID- 17519905
TI  - Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody
      against the extra domain B of fibronectin, in colorectal tumour models.
AB  - Angiogenesis is a characteristic feature of tumours and other disorders. The
      human monoclonal antibody L19- SIP targets the extra domain B of fibronectin, a
      marker of angiogenesis expressed in a range of tumours. The aim of this study was
      to investigate whole body distribution, tumour localisation and the potential of
      radioimmunotherapy with the L19-small immunoprotein (SIP) in colorectal tumours.
      Two colorectal tumour models with highly different morphologies, the SW1222 and
      LS174T xenografts, were used in this study. Localisation and retention of the L19
      SIP antibody at tumour vessels was demonstrated using immunohistochemistry and
      Cy3-labelled L19-SIP. Whole body biodistribution studies in both tumour models
      were carried out with (125)I-labelled L19-SIP. Finally, (131)I-labelled antibody
      was used to investigate the potential of radioimmunotherapy in SW1222 tumours.
      Using immunohistochemistry, we confirmed extra domain B expression in the tumour
      vasculature. Immunofluorescence demonstrated localisation and retention of
      injected Cy3-labelled L19-SIP at the abluminal side of tumour vessels.
      Biodistribution studies using a (125)I-labelled antibody showed selective tumour
      uptake in both models. Higher recorded values for localisation were found in the
      SW1222 tumours than in the LS174T (7.9 vs 6.6 %ID g(-1)), with comparable blood
      clearance for both models. Based on these results, a radioimmunotherapy study was
      performed in the SW1222 xenograft using (131)I-Labelled L19-SIP (55.5 MBq), which
      showed selective tumour uptake, tumour growth inhibition and improved survival.
      Radio- and fluorescence-labelled L19-SIP showed selective localisation and
      retention at vessels of two colorectal xenografts. Furthermore, (131)I-L19-SIP
      shows potential as a novel treatment of colorectal tumours, and provides the
      foundation to investigate combined therapies in the same tumour models.

PMID- 17519906
TI  - Angiosarcoma after radiotherapy: a cohort study of 332,163 Finnish cancer
      patients.
AB  - We evaluated the risk of angiosarcoma after radiotherapy among all patients with
      cancers of breast, cervix uteri, corpus uteri, lung, ovary, prostate, or rectum,
      and lymphoma diagnosed in Finland during 1953-2003, identified from the Finnish
      Cancer Registry. Only angiosarcomas of the trunk were considered, this being the
      target of radiotherapy for the first cancer. In the follow-up of 1.8 million
      person-years at risk, 19 angiosarcomas developed, all after breast and
      gynaecological cancer. Excess of angiosarcomas over national incidence rates were
      observed after radiotherapy without chemotherapy (standardised incidence ratio
      (SIR) 6.0, 95% confidence interval (CI) 2.7-11), after both radiotherapy and
      chemotherapy (SIR 100, 95% CI 12-360), and after other treatments (SIR 3.6, 95%
      CI 1.6-7.1). In the regression analysis however, the adjusted rate ratio for
      radiotherapy was 1.0 (95% CI 0.23-4.4). Although an increased risk of
      angiosarcoma among cancer patients is evident, especially with breast and
      gynaecological cancer, the excess does not appear to be strongly related to
      radiotherapy.

PMID- 17519907
TI  - The potential therapeutic role of lymph node resection in epithelial ovarian
      cancer: a study of 13918 patients.
AB  - The aim of the study is to determine the role of lymphadenectomy in advanced
      epithelial ovarian cancer. The data were obtained from the Surveillance,
      Epidemiology and End Results (SEER) program reported between 1988 and 2001.
      Kaplan-Meier estimates and Cox proportional hazards regression models were used
      for analysis. Of 13 918 women with stage III-IV epithelial ovarian cancer (median
      age: 64 years), 87.9% were Caucasian, 5.6% African Americans, and 4.4% Asians. A
      total of 4260 (30.6%) underwent lymph node dissections with a median number of
      six nodes reported. For all patients, a more extensive lymph node dissection (0,
      1, 2-5, 6-10, 11-20, and >20 nodes) was associated with an improved 5-year
      disease-specific survival of 26.1, 35.2, 42.6, 48.4, 47.5, and 47.8%,
      respectively (P<0.001). Of the stage IIIC patients with nodal metastases, the
      extent of nodal resection (1, 2-5, 6-10, 11-20, and >20 nodes) was associated
      with improved survivals of 36.9, 45.0, 47.8, 48.7, and 51.1%, respectively
      (P=0.023). On multivariate analysis, the extent of lymph node dissection and
      number of positive nodes were significant independent prognosticators after
      adjusting for age, year at diagnosis, stage, and grade of disease. The extent of
      lymphadenectomy is associated with an improved disease-specific survival of women
      with advanced epithelial ovarian cancer.

PMID- 17519908
TI  - Reducing uncertainty in health-care resource allocation.
AB  - A key task for health policymakers is to optimise the outcome of health care
      interventions. The pricing of a new generation of cancer drugs, in combination
      with limited health care resources, has highlighted the need for improved
      methodology to estimate outcomes of different treatment options. Here we
      introduce new general methodology, which for the first time employs continuous
      hazard functions for analysis of survival data. Access to continuous hazard
      functions allows more precise estimations of survival outcomes for different
      treatment options. We illustrate the methodology by calculating outcomes for
      adjuvant treatment of gastrointestinal stromal tumours with imatinib mesylate,
      which selectively inhibits the activity of a cancer-causing enzyme and is a
      hallmark representative for the new generation of cancer drugs. The calculations
      reveal that optimal drug pricing can generate all win situations that improve
      drug availability to patients, make the most of public expenditure on drugs and
      increase pharmaceutical company gross profits. The use of continuous hazard
      functions for analysis of survival data may reduce uncertainty in health care
      resource allocation, and the methodology can be used for drug price negotiations
      and to investigate health care intervention thresholds. Health policy makers,
      pharmaceutical industry, reimbursement authorities and insurance companies, as
      well as clinicians and patient organisations, should find the methodology useful.

PMID- 17519909
TI  - Is bilateral varicocele more detrimental to male fertility than unilateral
      varicocele?

PMID- 17519910
TI  - Can PSA velocity predict risk of death in men with prostate cancer?

PMID- 17519911
TI  - The Reynolds Risk Score: improved accuracy for cardiovascular risk prediction in
      women?

PMID- 17519912
TI  - Is alteplase safe and effective in routine clinical practice for patients with
      ischemic stroke?

PMID- 17519913
TI  - Risk profiling patients for selective use of drug-eluting stents is warranted.

PMID- 17519914
TI  - The estrogen paradox.

PMID- 17519915
TI  - Pegvisomant for the treatment of acromegaly-translation of clinical trials into
      clinical practice.

PMID- 17519916
TI  - Can serum thyroglobulin levels predict patient outcome after treatment of
      differentiated thyroid carcinoma?

PMID- 17519917
TI  - Pulmonary fibrosis in systemic sclerosis: is treatment with cyclophosphamide more
      effective than placebo?

PMID- 17519918
TI  - Should recommendations for colorectal-cancer screening be changed?

PMID- 17519919
TI  - Is rituximab maintenance therapy useful following rituximab salvage in refractory
      or relapsed follicular lymphoma?

PMID- 17519920
TI  - Probiotics for abdominal pain disorders in children--safe to use but are they
      helpful?

PMID- 17519921
TI  - Molecular imaging of brain amyloid in mild cognitive impairment and Alzheimer's
      disease.

PMID- 17519922
TI  - Measuring health-related quality of life in patients with end-stage renal
      disease: why and how.

PMID- 17519923
TI  - Lowering salt intake--an important strategy in the management of renal disease.

PMID- 17519924
TI  - Long-term outcome for lymph node-positive prostate cancer.
AB  - Although the number of men with lymph node-positive prostate cancer has declined,
      it is still significant and the challenge remains on how best to treat these
      patients. Only long-term follow-up can give a true indication of the outcome in
      prostate cancer. We evaluated our experience in treating lymph node-positive
      prostate cancer with a median follow-up of 10.2 years. The overall 5-year
      survival was 78% and the 10-year survival was 56%. Length of tumor control
      depends on the type of treatment given. Adding androgen ablation improves the
      duration of control dramatically, although optimal timing is still uncertain.

PMID- 17519925
TI  - Quality of life in young men after radical prostatectomy.
AB  - Urinary and sexual function and bother are important outcomes following radical
      prostatectomy (RP). Since urinary and sexual function are age-related, post
      operative bother may vary by age. This study explores the disease-specific
      quality-of-life outcomes in young men compared with older men undergoing RP.
      Using CaPSURE data, we identified men who underwent RP and completed the UCLA
      Prostate Cancer Index (PCI) before and 1-year post-RP. Men were stratified by age
      (< 55 years, 55-64, > or = 65). Multivariate regression models were created: a
      linear model for predictors of PCI scores and a logistic model for predictors of
      severe declines in PCI domains. Younger men scored significantly better than
      older men in urinary function (P=0.04), urinary bother (P=0.02) and sexual
      function (P<0.0001) 1-year post-RP. Severe declines in urinary bother (odds ratio
      (OR)=1.54, 1.01-2.35) and sexual function (OR=3.20, 1.97-5.19) were more common
      in men > or = 65 years. Men with relationships had less urinary bother (P=0.03)
      and were less likely to experience severe worsening of urinary bother (OR=0.32,
      0.17-0.60) while having a greater risk of severe worsening of sexual bother
      (OR=2.74, 1.28-5.89). The use of sexual aids was associated with worse sexual
      bother (P<0.0001) and greater risk of severe worsening of sexual bother (OR=2.29,
      1.54-3.30). Baseline PCI scores were independent predictors in all models. One
      year after RP, younger men (age < 55) have similar, or better, urinary and sexual
      function and bother. Baseline scores are strongly associated with post-RP scores
      and severity of declines. Current relationships and use of sexual aids have
      significant roles in post-RP bother.

PMID- 17519926
TI  - Fruit, vegetable, vitamin A intakes, and prostate cancer risk.
AB  - Prostate cancer risk was examined in relation to intakes of fruit, vegetables,
      beta-carotene and retinol. Subjects were a cohort of 1985 men previously to
      asbestos who participated in a cancer prevention programme of beta-carotene and
      retinol supplements that commenced in July 1990. Diet was assessed at entry to
      the programme. Ninety-seven cases of prostate cancer were identified during
      follow-up until the end of 2004. A decreased prostate cancer risk was observed
      with increasing intakes of vitamin C-rich vegetables, including bell peppers and
      broccoli. Fruit, other vegetables and vitamin A intakes did not appear to be
      strong factors in the development of prostate cancer in this study.

PMID- 17519927
TI  - A selected review and personal experience with robotic prostatectomy:
      implications for adoption of this new technology in the United Kingdom.
AB  - Robot-assisted laparoscopic prostatectomy (RALP) is a rapidly evolving technique
      for the treatment of localized prostate cancer. However, cynics point to the
      increasing role of market forces in the robotic revolution. As yet, Europe has
      not taken up RALP in large numbers and this may in part relate to the high level
      of expertise in laparoscopy previously gained. Furthermore, setting up a robotic
      programme is a major undertaking for many surgical units. This review discusses
      some of the challenges in the development of a robotic service drawn from
      personal experience within the United Kingdom. Furthermore, available data on
      RALP versus open and laparoscopic approaches are reviewed for surgical and cancer
      related outcomes. Preliminary data appear to show an advantage over open
      prostatectomy with reduced blood loss, decreased pain and early mobilisation and
      shorter hospital stay. Most intra-institutional studies demonstrate better
      postoperative continence and potency with RALP; however, this needs to be viewed
      in the context of a paucity of randomized data available in the literature. There
      is no definitive data to show an advantage over standard laparoscopic surgery,
      but the fact that this technique has reached parity with laparoscopy within 5
      years is encouraging: with continued experience, the hope is that results will
      continue to improve.

PMID- 17519928
TI  - Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating
      individual differences in human personality.
AB  - Little is known about neural mechanisms underlying human personality and
      temperament, despite their considerable importance as highly heritable risk
      mediators for somatic and psychiatric disorders. To identify these circuits, we
      used a combined genetic and imaging approach focused on Monoamine Oxidase A
      (MAOA), encoding a key enzyme for monoamine metabolism previously associated with
      temperament and antisocial behavior. Male carriers of a low-expressing genetic
      variant exhibited dysregulated amygdala activation and increased functional
      coupling with ventromedial prefrontal cortex (vmPFC). Stronger coupling predicted
      increased harm avoidance and decreased reward dependence scores, suggesting that
      this circuitry mediates a part of the association of MAOA with these traits. We
      utilized path analysis to parse the effective connectivity within this system,
      and provide evidence that vmPFC regulates amygdala indirectly by influencing
      rostral cingulate cortex function. Our data implicate a neural circuit for
      variation in human personality under genetic control, provide an anatomically
      consistent mechanism for vmPFC-amygdala interactions underlying this variation,
      and suggest a role for vmPFC as a superordinate regulatory area for emotional
      arousal and social behavior.

PMID- 17519929
TI  - Infant serotonin transporter (SLC6A4) promoter genotype is associated with
      adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor
      medications.
AB  - Reduced Apgar scores and birth weight, increased risk of respiratory distress,
      jitteriness and increased tone have been reported in up to 30% of neonates with
      prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressant
      medications. In adults, effects of these medications may be related to the
      genotype for the serotonin transporter (SLC6A4) promoter. In this study we
      investigated whether SLC6A4 genotype influences the risk for adverse outcomes in
      neonates with prenatal SRI exposure. Neonatal outcomes including Apgar scores,
      birth weight, gestational age at birth, symptoms of poor neonatal adaptation and
      genotype for SLC6A4 were determined in 37 prenatally SRI exposed neonates and
      compared with 47 non-exposed neonates. Reduced 5 min Apgar scores were observed
      in exposed neonates and this was moderated by the ss genotype (P<0.001). Birth
      weight was lower in exposed ls neonates (P=0.008). Risk for respiratory symptoms
      (respiratory distress and rapid breathing) was higher in exposed neonates with
      the ll genotype compared to non-exposed neonates (P<0.05) and risk for neuromotor
      symptoms increased in exposed ss neonates (P<0.026). These relationships remained
      when controlling for maternal mood during pregnancy, length of gestational
      medication exposure and gestational age at birth and cesarean section rate.
      Prenatal SRI exposure was associated with adverse neonatal outcomes and these
      effects were moderated by infant SLC6A4 genotype. Relationships between
      polymorphisms and specific outcomes varied during the neonatal period, suggesting
      that beyond apparent gene-medication interactions, multiple mechanisms contribute
      to adverse neonatal outcomes following prenatal SRI exposure.

PMID- 17519931
TI  - Protecting the tract.

PMID- 17519932
TI  - Alzheimer's and the immune system.

PMID- 17519935
TI  - Categorizing pain and distress in a Parkinson's model. Gimme an 'E'.

PMID- 17519936
TI  - Categorizing pain and distress in a Parkinson's model.

PMID- 17519937
TI  - Categorizing pain and distress in a Parkinson's model. Category E (with caveats).

PMID- 17519938
TI  - Categorizing pain and distress in a Parkinson's model. Depends on context.

PMID- 17519939
TI  - Sudden onset of mortality within a colony of FVB/n mice.

PMID- 17519941
TI  - Psittacine bird crop gavage feeding.

PMID- 17519942
TI  - A current perspective on the role and needs of IACUC unaffiliated members.
AB  - To be considered properly constituted, an IACUC must include at least one member
      who is unaffiliated with the research institution. The unaffiliated member, whose
      role on the Committee is to represent the general public, is often a non
      scientist with little or no previous exposure to the concepts described in the
      animal-use protocols he or she is charged with reviewing. Needless to say, this
      knowledge gap can present problems. The author, himself an unaffiliated IACUC
      member, provides advice for those who may choose to serve in this capacity and
      suggestions for the institutions that rely on their services.

PMID- 17519943
TI  - The basics of animal biosafety and biocontainment training.
AB  - The threat of biocontamination in an animal facility is best subdued by training.
      'Training' is an ambiguous designation that may not be adequately appreciated in
      all animal facilities. The authors set down concrete training topics and provide
      practical advice on incorporating the basic principles of facility biosafety
      training--as well as the precautions and procedures that employees must know in
      case of accident or emergency--into various training models. They also discuss
      the current biosafety publications and guidelines and their relationship to
      biosafety training.

PMID- 17519944
TI  - Use of behavior analysis to recognize pain in small mammals.
AB  - The minimization of pain in laboratory animals is a gold standard with
      implications for improvements in both animal welfare and research quality.
      Changes in behavioral parameters may indicate that an animal is in pain, but in
      order to effectively use behavioral change to assess pain, the observer must be
      familiar with normal behaviors. The author discusses normal and pain-related
      behaviors exhibited by rodents, rabbits, and ferrets.

PMID- 17519945
TI  - The nematode neuropeptide, AF2 (KHEYLRF-NH2), increases voltage-activated calcium
      currents in Ascaris suum muscle.
AB  - BACKGROUND AND PURPOSE: Resistance to all the classes of anti-nematodal drugs
      like the benzimidazoles, cholinergic agonists and avermectins, has now been
      recorded in parasites of animals and/or humans. The development of novel
      anthelmintics is an urgent and imperative need. Receptors of nematode
      neuropeptides have been suggested to be suitable target sites for novel
      anthelmintic drugs. EXPERIMENTAL APPROACH: To investigate the effect of AF2 on
      calcium-currents in Ascaris suum somatic muscle cells we employed the two
      micropipette current-clamp and voltage-clamp techniques and a brief application
      of AF2. KEY RESULTS: Here we report the isolation of voltage-activated,
      transient, inward calcium currents. These currents are similar in characteristics
      to Caenorhabditis elegans UNC-2 type currents, non-L-type calcium currents.
      Following a 2-minute application of 1 microM AF2 , there was a significant long
      lasting increase in the transient inward calcium current; AF2 increased the
      maximum current (from -84 nA to -158 nA) by shifting the threshold in the
      hyperpolarising direction (V (50) changed from -7.2 to -12.8 mV) and increasing
      the maximum conductance change from 1.91 to 2.94 microS. CONCLUSION AND
      IMPLICATIONS: These studies demonstrate a mechanism by which AF2 increased the
      excitability of the neuromuscular system by modulating calcium currents in
      nematodes. A selective small molecule agonist of the AF2 receptor is predicted to
      increase the contraction and act synergistically with cholinergic anthelmintics
      and could counter resistance to these compounds.

PMID- 17519946
TI  - Kisspeptins: a multifunctional peptide system with a role in reproduction, cancer
      and the cardiovascular system.
AB  - Orphan G-protein-coupled receptors that have recently been paired with their
      cognate ligand are an often untapped resource for novel drug development. The
      KISS1 receptor (previously designated GPR54) has been paired with biologically
      active cleavage peptides of the KiSS-1 gene product, the kisspeptins (KP). The
      focus of this review is the emerging pharmacology and physiology of the KP.
      Genetic linkage analysis in humans revealed that mutations in KISS1 (GPR54,
      AXOR12 or hOT7T175) result in idiopathic hypogonadotrophic hypogonadism and
      knockout mouse studies confirmed this finding. Identification of KISS1 (GPR54) as
      a molecular switch for puberty subsequently led to the discovery that KP activate
      the GnRH cascade. Prior to the role of KISS1 (GPR54) in puberty being described,
      KP had been shown to be inhibitors of tumour metastasis across a range of
      cancers. Subsequently the mechanism of this inhibition has been suggested to be
      via altered cell motility and adhesiveness. PCR detected highest expression of KP
      and KISS1 (GPR54) in placenta, and changes in KP levels throughout pregnancy and
      expression in trophoblasts suggests a role in placentation. Placentation and
      metastasis are invasive processes that require angiogenesis. Investigation of
      KISS1 (GPR54) and KP in vasculature revealed discrete localisation of KISS1
      (GPR54) to blood vessels prone to atherosclerosis and a potent vasoconstrictor
      action. A role for KP has also been shown in whole body homeostasis. KP are
      multifunctional peptides and further investigation is required to fully elucidate
      the complex pathways regulated by these peptides and how these pathways integrate
      in the whole body system.

PMID- 17519947
TI  - Dexrazoxane prevents doxorubicin-induced long-term cardiotoxicity and protects
      myocardial mitochondria from genetic and functional lesions in rats.
AB  - BACKGROUND AND PURPOSE: Doxorubicin causes a chronic cardiomyopathy in which
      reactive oxygen species (ROS) accumulate over time and are associated with
      genetic and functional lesions of mitochondria. Dexrazoxane is a cardioprotective
      iron chelator that interferes with ROS production. We aim to analyze the effects
      of dexrazoxane on mitochondria in the prevention of doxorubicin-induced chronic
      myocardial lesions. EXPERIMENTAL APPROACH: Wistar rats (11 weeks of age) were
      injected with intravenous doxorubicin (0.8 mg kg(-1) weekly for 7 weeks) with or
      without simultaneous dexrazoxane (8 mg kg(-1)). Animals were killed at 48 weeks.
      Cardiomyopathy was scored clinically and histologically and cardiac mitochondria
      were analyzed. KEY RESULTS: Compared to control rats receiving saline, rats
      treated with doxorubicin alone developed a clinical, macroscopic, histological
      and ultrastructural cardiomyopathy with low cytochrome c-oxidase (COX) activity
      (26% of controls). The expression of the mtDNA-encoded COX II subunit was reduced
      (64% of controls). Myocardia exhibited a high production of ROS (malondialdehyde
      338% and superoxide 787% of controls). Mitochondria were depleted of
      mitochondrial DNA (mtDNA copy number 46% of controls) and contained elevated
      levels of mtDNA deletions. Dexrazoxane co-administration prevented all these
      effects of doxorubicin on mitochondria, except that hearts co-exposed to
      doxorubicin and dexrazoxane had a slightly lower mtDNA content (81% of controls)
      and mtDNA deletions at low frequency. CONCLUSIONS AND IMPLICATIONS: Dexrazoxane
      prevented doxorubicin induced late-onset cardiomyopathy and also protected the
      cardiac mitochondria from acquired ultrastructural, genetic and functional
      damage.

PMID- 17519948
TI  - Blockade of MCH1 receptor signalling ameliorates obesity and related hepatic
      steatosis in ovariectomized mice.
AB  - BACKGROUND AND PURPOSE: Melanin-concentrating hormone (MCH) is a cyclic
      orexigenic neuropeptide predominantly expressed in the lateral hypothalamus. We
      investigated the roles of MCH1 receptor signalling in ovariectomy (OVX)-induced
      obesity in female C57BL/6J mice, an animal model of postmenopausal obesity.
      EXPERIMENTAL APPROACH: The effects of blocking signalling via the MCH1 receptor
      on OVX-induced obesity was investigated by using Mch1r deficient (KO) mice and
      chronic treatment with a selective MCH1 receptor antagonist. KEY RESULTS: OVX
      induced body weight gain and increases in the weight of visceral fat and of
      liver; these effects were attenuated following OVX in Mch1r KO mice. OVX-induced
      triglyceride (TG) accumulation and elevated expression of lipogenic genes were
      significantly ameliorated in the liver of Mch1r KO mice. In agreement with these
      results, chronic i.c.v. infusion of a selective MCH1 receptor antagonist
      significantly reduced body weight gain, visceral fat and liver weights in OVX
      mice, and hepatic TG contents and lipogenic gene expression levels were
      normalized. CONCLUSION AND IMPLICATIONS: Our results indicate that MCH1 receptor
      signalling is involved in the development of fatty liver, as well as obesity, in
      OVX mice, and suggest a therapeutic potential for MCH1 receptor antagonists in
      the treatment of obesity and fatty liver.

PMID- 17519949
TI  - Mitochondrial medicine: pharmacological targeting of mitochondria in disease.
AB  - Mitochondria play a central role in cell life and death and are known to be
      important in a wide range of diseases including the cancer, diabetes,
      cardiovascular disease, and the age-related neurodegenerative diseases. The
      unique structural and functional characteristics of mitochondria enable the
      selective targeting of drugs designed to modulate the function of this organelle
      for therapeutic gain. This review discusses mitochondrial drug targeting
      strategies and a variety of novel mitochondrial drug targets including the
      electron transport chain, mitochondrial permeability transition, Bcl-2 family
      proteins and mitochondrial DNA. Mitochondrial drug-targeting strategies will open
      up avenues for manipulating mitochondrial functions and allow for selective
      protection or eradication of cells for therapeutic gain in a variety of diseases.

PMID- 17519950
TI  - Molecular expression and pharmacological identification of a role for K(v)7
      channels in murine vascular reactivity.
AB  - BACKGROUND AND PURPOSE: This study represents a novel characterisation of KCNQ
      encoded potassium channels in the vasculature using a variety of pharmacological
      and molecular tools to determine their role in contractility. EXPERIMENTAL
      APPROACH: Reverse transcriptase polymerase chain reaction (RT-PCR) experiments
      were undertaken on RNA isolated from mouse aorta, carotid artery, femoral artery
      and mesenteric artery using primers specific for all known KCNQ genes. RNA
      isolated from mouse heart and brain were used as positive controls.
      Pharmacological experiments were undertaken on segments from the same blood
      vessels to determine channel functionality. Immunocytochemical experiments were
      performed on isolated myocytes from thoracic aorta. KEY RESULTS: All blood
      vessels expressed KCNQ1, 4 and 5 with hitherto 'neuronal' KCNQ4 being,
      surprisingly, the most abundant. The correlated proteins K(v)7.1, K(v)7.4 and
      K(v)7.5 were identified in the cell membranes of aortic myocytes by
      immunocytochemistry. Application of three compounds known to activate K(v)7
      channels, retigabine (2 -20 microM), flupirtine (20 microM) and meclofenamic acid
      (20 microM), relaxed vessels precontracted by phenylephrine or 1 mM 4
      aminopyridine but had no effect on contractions produced by 60 mM KCl or the
      K(v)7 channel blocker XE991 (10 microM). All vessels tested contracted upon
      application of the K(v)7 channel blockers XE991 and linopirdine (0.1-10 microM).
      CONCLUSIONS AND IMPLICATIONS: Murine blood vessels exhibit a distinctive KCNQ
      expression profile with 'neuronal' KCNQ4 dominating. The ion channels encoded by
      KCNQ genes have a crucial role in defining vascular reactivity as K(v)7 channel
      blockers produced marked contractions whereas K(v)7 channel activators were
      effective vasorelaxants.

PMID- 17519951
TI  - A-272651, a nonpeptidic blocker of large-conductance Ca2+-activated K+ channels,
      modulates bladder smooth muscle contractility and neuronal action potentials.
AB  - BACKGROUND AND PURPOSE: The large-conductance Ca(2+)-activated K(+) channel
      (BK(Ca), K(Ca)1.1) links membrane excitability with intracellular Ca(2+)
      signaling and plays important roles in smooth muscle contraction, neuronal
      firing, and neuroendocrine secretion. This study reports the characterization of
      a novel BK(Ca) channel blocker, 2,4-dimethoxy-N-naphthalen-2-yl-benzamide (A
      272651). EXPERIMENTAL APPROACH: (86)Rb(+) efflux in HEK-293 cells expressing
      BK(Ca) was measured. Effects of A-272651 on BK(Ca) alpha- and BK(Ca) alphabeta1
      mediated currents were evaluated by patch-clamp. Effects on contractility were
      assessed using low-frequency electrical field stimulated pig detrusor and
      spontaneously contracting guinea pig detrusor. Effects of A-272651 on neuronal
      activity were determined in rat small diameter dorsal root ganglia (DRG). KEY
      RESULTS: A-272651 (10 microM) inhibited (86)Rb(+) efflux evoked by NS-1608 in HEK
      293 cells expressing BK(Ca) currents. A-272651 concentration-dependently
      inhibited BK(Ca) currents with IC(50) values of 4.59 microM (Hill coefficient
      1.04, measured at +40 mV), and 2.82 microM (Hill coefficient 0.89), respectively,
      for BK(Ca) alpha and BK(Ca) alphabeta1-mediated currents. Like iberiotoxin, A
      272651 enhanced field stimulated twitch responses in pig detrusor and spontaneous
      contractions in guinea pig detrusor with EC(50) values of 4.05+/-0.05 and 37.95+/
      0.12 microM, respectively. In capsaicin-sensitive DRG neurons, application of A
      272651 increased action potential firing and prolonged action potential duration.
      CONCLUSIONS AND IMPLICATIONS: These data demonstrate that A-272651 modulates
      smooth muscle contractility and neuronal firing properties. Unlike previously
      reported peptide BK(Ca) blockers, A-272651 represents one of the first small
      molecule BK(Ca) channel blockers that could serve as a useful tool for further
      characterization of BK(Ca) channels in physiological and pathological states.

PMID- 17519952
TI  - Mutations at F637 in the NMDA receptor NR2A subunit M3 domain influence agonist
      potency, ion channel gating and alcohol action.
AB  - BACKGROUND AND PURPOSE: NMDA receptors are important molecular targets of ethanol
      action in the CNS. Previous studies have identified a site in membrane-associated
      domain 3 (M3) of the NR1 subunit and two sites in M4 of the NR2A subunit that
      influence alcohol action; the sites in NR2A M4 also regulate ion channel gating.
      The purpose of this study was to determine whether mutations at the site in the
      NR2A subunit corresponding to the NR1 M3 site influence alcohol action and ion
      channel gating. EXPERIMENTAL APPROACH: We investigated the effects of mutations
      at phenylalanine (F) 637 of the NR2A subunit using whole-cell and single-channel
      patch-clamp electrophysiological recording in transiently-transfected HEK 293
      cells. KEY RESULTS: Mutations at F637 in the NR2A subunit altered peak and steady
      state glutamate EC(50) values, maximal steady-state to peak current ratios
      (I(ss):I(p)), mean open time, and ethanol IC(50) values. Differences in glutamate
      potency among the mutants were not due to changes in desensitization. Ethanol
      IC(50) values were significantly correlated with glutamate EC(50) values, but not
      with maximal I(ss):I(p) or mean open time. Ethanol IC(50) values were linearly
      and inversely related to molecular volume of the substituent. CONCLUSIONS AND
      IMPLICATIONS: These results demonstrate that NR2A(F637) influences NMDA receptor
      affinity, ion channel gating, and ethanol sensitivity. The changes in NMDA
      receptor affinity are likely to be the result of altered ion channel gating. In
      contrast to the cognate site in the NR1 subunit, the action of ethanol does not
      appear to involve occupation of a critical volume at NR2A(F637).

PMID- 17519953
TI  - When a friend can become an enemy! Recognition and management of metformin
      associated lactic acidosis.

PMID- 17519954
TI  - Association of osteopontin gene haplotypes with nephrolithiasis.
AB  - Osteopontin (OPN) is one of the glycosylated phosphoproteins produced in the
      kidney that can modulate nephrolithiasis. We had previously found a modest
      association between OPN gene polymorphisms and the risk for urinary stone
      formation. In order to determine if sequence variants within the OPN gene could
      be linked to the risk of nephrolithiasis; we sequenced the entire OPN gene of 45
      stone forming patients and 54 control patients of Japanese ancestry. We
      identified 61 polymorphisms and of these evaluated four haplotype-tagging single
      nucleotide polymorphisms in a total of 126 kidney stone cases and 214 healthy
      individuals; all of Japanese ancestry. There was a significant association of two
      of these haplotypes located in the OPN promoter with the relative probability of
      nephrolithiasis; one of increased and one of reduced risk. Our findings provide
      potential support for significant increased and decreased associations between
      OPN gene haplotypes and the relative potential of stone formation in the Japanese
      population. We suggest that such genetic findings may help to clarify the
      function of OPN in nephrolithiasis.

PMID- 17519955
TI  - Heparanase in glomerular diseases.
AB  - Heparanase is an endo-beta(1-4)-D-glucuronidase that degrades heparan sulfate
      (HS) polysaccharide side chains. The role of heparanase in metastasis,
      angiogenesis, and inflammation has been established. Recent data suggest a role
      for heparanase in several proteinuric diseases and an increased glomerular
      heparanase expression is associated with loss of HS in the glomerular basement
      membrane (GBM). Furthermore, an increase in heparanase activity was detected in
      urine from proteinuric patients. Mice with transgenic heparanase overexpression
      developed mild proteinuria. Glomerular heparanase activity is proposed to lead to
      loss of HS in the GBM and proteinuria. Because the primary role of GBM HS for
      charge-selective permeability has been questioned recently, heparanase may induce
      or enhance proteinuria by (i) changes in the glomerular cell-GBM interactions,
      due to loss of HS; (ii) release of HS-bound factors and HS fragments in
      glomeruli; or (iii) intracellular signaling by binding of heparanase to
      glomerular cells. Which of these mechanisms is prevailing requires further
      research. The precise mechanisms leading to increased heparanase expression in
      the different glomerular cell types remain elusive, but may involve
      hyperglycemia, angiotensin II, aldosterone, and reactive oxygen species. This
      review focuses on the role of heparanase in HS degradation in proteinuric
      diseases and the possibility/feasibility of heparanase inhibitors, such as
      heparin(oids), as treatment options.

PMID- 17519956
TI  - A mouse model of autosomal recessive polycystic kidney disease with biliary duct
      and proximal tubule dilatation.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in
      the polycystic kidney and hepatic disease (PKHD1) gene encoding the protein
      fibrocystin/polyductin. The aim of our study was to produce a mouse model of
      ARPKD in which there was no functional fibrocystin/polyductin to study the
      pathophysiology of cystic and fibrocystic disease in renal and non-renal tissues.
      Exon 2 of the gene was deleted and replaced with a neomycin resistance cassette
      flanked by loxP sites, which could be subsequently removed by Cre-lox
      recombinase. Homozygous Pkhd1(del2/del2) mice were viable, fertile and exhibited
      hepatic, pancreatic, and renal abnormalities. The biliary phenotype displayed
      progressive bile duct dilatation, resulting in grossly cystic and fibrotic livers
      in all animals. The primary cilia in the bile ducts of these mutant mice had
      structural abnormalities and were significantly shorter than those of wild-type
      (WT) animals. The Pkhd1(del2/del2) mice often developed pancreatic cysts and some
      exhibited gross pancreatic enlargement. In the kidneys of affected female mice,
      there was tubular dilatation of the S3 segment of the proximal tubule (PT)
      starting at about 9 months of age, whereas male mice had normal kidneys up to 18
      months of age. Inbreeding the mutation onto BALBc/J or C57BL/6J background mice
      resulted in females developing PT dilatation by 3 months of age. These inbred
      mice will be useful resources for studying the mechanisms underlying the
      pathogenesis of ARPKD.

PMID- 17519957
TI  - Influence of aging on cytoplasmic incompatibility, sperm modification and
      Wolbachia density in Culex pipiens mosquitoes.
AB  - Wolbachia are maternally inherited endocellular bacteria, widespread in
      invertebrates and capable of altering several aspects of host reproduction.
      Cytoplasmic incompatibility (CI) is commonly found in arthropods and induces
      hatching failure of eggs from crosses between Wolbachia-infected males and
      uninfected females (or females infected by incompatible strains). Several factors
      such as bacterial and host genotypes or bacterial density contribute to CI
      strength and it has been proposed, mostly from Drosophila data, that older males
      have a lower Wolbachia load in testes which, thus, induces a lighter CI. Here, we
      challenge this hypothesis using different incompatible Culex pipiens mosquito
      strains and show that CI persists at the same intensity throughout the mosquito
      life span. Embryos from incompatible crosses showed even distributions of
      abortive phenotypes over time, suggesting that host ageing does not reduce the
      sperm-modification induced by Wolbachia. CI remained constant when sperm was
      placed in the spermathecae of incompatible females, indicating that sperm
      modification is also stable over time. The capacity of infected females to rescue
      CI was independent of age. Last, the density of Wolbachia in whole testes was
      highly strain-dependent and increased dramatically with age. Taken together,
      these data stress the peculiarity of the C.pipiens/Wolbachia interaction and
      suggest that the bacterial dosage model should be rejected in the case of this
      association.

PMID- 17519958
TI  - Cigarette smoking, cytogenetic abnormalities, and acute myelogenous leukemia.

PMID- 17519959
TI  - Essential thrombocythemia in young individuals: frequency and risk factors for
      vascular events and evolution to myelofibrosis in 126 patients.
AB  - The frequency of vascular events and evolution to myelofibrosis (MF) in young
      individuals with essential thrombocythemia (ET) is not well known. The incidence
      and predisposing factors to such complications was studied in 126 subjects
      diagnosed with ET at a median age of 31 years (range: 5-40). Overall survival and
      probability of survival free of thrombosis, bleeding and MF were analyzed by the
      Kaplan-Meier method and the presence of the Janus Kinase 2 (JAK2) V617F mutation
      correlated with the appearance of such complications. The JAK2 mutation (present
      in 43% of patients) was associated with higher hemoglobin (Hb) (P<0.001) and
      lower platelets at diagnosis. With a median follow-up of 10 years (range: 4-25),
      31 thrombotic events were registered (incidence rate: 2.2 thromboses/100
      patients/year). When compared with the general population, young ET patients
      showed a significant increase in stroke (odds ratio 50, 95% CI: 21.5-115) and
      venous thromboses (odds ratio 5.3, 95% CI: 3.9-10.6). Thrombosis-free survival
      was 84% at 10 years, with tobacco use being associated with higher risk of
      thrombosis. Actuarial freedom from evolution to MF was 97% at 10 years. In
      conclusion, young ET patients have thrombotic events, especially stroke and
      venous thrombosis, more frequently than generally considered, whereas they rarely
      transform to MF.

PMID- 17519960
TI  - Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with
      ABCG2 on primitive hematopoietic stem cells.
AB  - The majority of chronic phase chronic myeloid leukemia (CML) patients treated
      with the tyrosine kinase inhibitor (TKI) imatinib mesylate maintain durable
      responses to the drug. However, most patients relapse after withdrawal of
      imatinib and advanced stage patients often develop drug resistance. As CML is
      considered a hematopoietic stem cell cancer, it has been postulated that inherent
      protective mechanisms lead to relapse in patients. The ATP binding-cassette
      transporters ABCB1 (MDR-1; P-glycoprotein) and ABCG2 are highly expressed on
      primitive hematopoietic stem cells (HSCs) and have been shown to interact with
      TKIs. Herein we demonstrate a dose-dependent, reversible inhibition of ABCG2
      mediated Hoechst 33342 dye efflux in primary human and murine HSC by both
      imatinib and nilotinib (AMN107), a novel aminopyrimidine inhibitor of BCR-ABL.
      ABCG2-transduced K562 cells were protected from imatinib and nilotinib-mediated
      cell death and from downregulation of P-CRKL. Moreover, photoaffinity labeling
      revealed interaction of both TKIs with ABCG2 at the substrate binding sites as
      they compete with the binding of [(125)I] IAAP and also stimulate the
      transporter's ATPase activity. Therefore, our evidence suggests for the role of
      ABC transporters in resistance to TKI on primitive HSCs and CML stem cells and
      provides a rationale how TKI resistance can be overcome in vivo.

PMID- 17519961
TI  - The multifunctional nucleolus.
AB  - The nucleolus is a distinct subnuclear compartment that was first observed more
      than 200 years ago. Nucleoli assemble around the tandemly repeated ribosomal DNA
      gene clusters and 28S, 18S and 5.8S ribosomal RNAs (rRNAs) are transcribed as a
      single precursor, which is processed and assembled with the 5S rRNA into ribosome
      subunits. Although the nucleolus is primarily associated with ribosome
      biogenesis, several lines of evidence now show that it has additional functions.
      Some of these functions, such as regulation of mitosis, cell-cycle progression
      and proliferation, many forms of stress response and biogenesis of multiple
      ribonucleoprotein particles, will be discussed, as will the relation of the
      nucleolus to human diseases.

PMID- 17519962
TI  - Selection on MHC-linked microsatellite loci in sheep populations.
AB  - Microsatellites within the major histocompatibility complex (MHC) region have
      received increasing attention as proxy measures of the level of polymorphism at
      the Mhc genes themselves. We assessed the diversity of microsatellite loci within
      or in close proximity of the Mhc genes in several breeds of domestic sheep (Ovis
      aries) and the wild Mouflon (Ovis orientalis musimon). This was compared to
      variation at other microsatellite loci scattered throughout the sheep genome.
      Significantly higher number of alleles were observed at the MHC microsatellites.
      The sheep breeds studied fell into high- and low-diversity group. This grouping
      is not related to the agricultural use of the breeds, whether for milk, meat or
      wool. It is, however, correlated with the geographic origins of the breeds.
      Southern breeds are genetically more diverse than northern breeds. The observed
      heterozygosity was in most cases lower than Hardy-Weinberg expectations. The
      potential impact of selective breeding by man on this is discussed. Neutrality
      tests indicated that for most of the breeds, the distribution of alleles at the
      MHC-linked microsatellites are more even than would be expected if the genes were
      neutral and sampled from populations under drift-mutation equilibrium.
      Hitchhiking due to tight linkage with alleles at the MHC loci that are under
      balancing selection is proposed as a possible explanation for this pattern.

PMID- 17519963
TI  - Inferring gene flow in coral reef fishes from different molecular markers: which
      loci to trust?
AB  - Contrasting results are usually reported in the literature regarding the factors
      influencing observed structuring of genetic variability. The goals of this study
      were, for five coral reef fishes in French Polynesia, (1) to infer the
      theoretical variance of single locus F(ST) estimates expected under neutrality in
      order to exclude outlier loci before inferring gene flow and (2) to test
      thereafter whether species laying pelagic eggs effectively disperse more than
      species laying benthic eggs in this system. For this purpose, a total of 952
      individuals from five species belonging to two families (Chaetodontidae and
      Pomacentridae) were screened among populations sampled within a 60-600 km spatial
      range for intron length polymorphism at 11 loci in order to illuminate
      contrasting results previously published on allozymes and mitochondrial DNA
      (mtDNA) control region polymorphisms. Statistically speaking, among the five
      species, four loci (three allozymes and one intron) were identified as outliers
      and discarded before interpretation of genetic differentiation in terms of
      effective dispersal. Biologically speaking, our results suggest that the observed
      genetic structure is not significantly related to the reproductive strategy of
      coral reef fish in the island system we analysed and that observed random genetic
      differentiation accommodates Wright's island model in all five species surveyed.
      Overall, our study emphasizes how cautious one has to be when trying to interpret
      present-day genetic structure in terms of gene flow while using a limited number
      of loci and/or different sets of loci.

PMID- 17519964
TI  - Phylogeography of a ground beetle species in La Gomera (Canary Islands): the
      effects of landscape topology and population history.
AB  - Paraeutrichopus pecoudi (Coleoptera, Carabidae) is a species endemic to the
      mountain laurel forests of La Gomera in the Canary archipelago. La Gomera is an
      island of volcanic origin (9.4 mya), where a well-preserved laurel forest is
      partly fragmented by valleys and ridges. Historically restricted gene flow with
      isolation by distance are deduced at different clade levels for P. pecoudi
      populations, an expected scenario arising from landscape discontinuity, which has
      caused local isolation of these flightless insects. Methodological considerations
      were investigated for nested clade phylogeographic analysis (NCPA), comparing the
      results obtained using either (a) pairwise distances between collecting sites
      measured as surface (route) distances or (b) standard geographical distances
      calculated from latitude-longitude coordinates. Some differences were found in
      the NCPA statistics and associated inferences at the higher clade levels in
      relation to the assumed distance criteria. Coalescent simulations and posterior
      automated NCPAs assuming different geographical distances were performed to test
      the robustness of the method when considering the distances used. These analyses
      showed no significant differences in NCPA conclusions, and the scenario of
      restricted gene flow was recovered using both distance calculators at the same
      rate, although the parameter statistics were slightly different. We suggest that
      in landscapes with extreme topography, geographical distances separating
      populations are certainly underestimated by standard techniques. More complex and
      explicit descriptions of the potential dispersal of terrestrial organisms should
      be explored for implementation in statistical phylogeography in such cases.

PMID- 17519965
TI  - EST-SSRs as a resource for population genetic analyses.
AB  - Simple-sequence repeats (SSRs) have increasingly become the marker of choice for
      population genetic analyses. Unfortunately, the development of traditional
      'anonymous' SSRs from genomic DNA is costly and time-consuming. These problems
      are further compounded by a paucity of resources in taxa that lack clear economic
      importance. However, the advent of the genomics age has resulted in the
      production of vast amounts of publicly available DNA sequence data, including
      large collections of expressed sequence tags (ESTs) from a variety of different
      taxa. Recent research has revealed that ESTs are a potentially rich source of
      SSRs that reveal polymorphisms not only within the source taxon, but in related
      taxa, as well. In this paper, we review what is known about the transferability
      of EST-SSRs from one taxon to another with particular reference to the potential
      of these markers to facilitate population genetic studies. As an example of the
      utility of these resources, we then cross-reference existing EST databases
      against lists of rare, endangered and invasive plant species and conclude that
      half of all suitable EST databases could be exploited for the population genetic
      analysis of species of conservation concern. We then discuss the advantages and
      disadvantages of EST-SSRs in the context of population genetic applications.

PMID- 17519966
TI  - Evaluating the role of natural selection in the evolution of gene regulation.
AB  - Surveys of gene expression reveal extensive variability both within and between a
      wide range of species. Compelling cases have been made for adaptive changes in
      gene regulation, but the proportion of expression divergence attributable to
      natural selection remains unclear. Distinguishing adaptive changes driven by
      positive selection from neutral divergence resulting from mutation and genetic
      drift is critical for understanding the evolution of gene expression. Here, we
      review the various methods that have been used to test for signs of selection in
      genomic expression data. We also discuss properties of regulatory systems
      relevant to neutral models of gene expression. Despite some potential caveats,
      published studies provide considerable evidence for adaptive changes in gene
      expression. Future challenges for studies of regulatory evolution will be to
      quantify the frequency of adaptive changes, identify the genetic basis of
      expression divergence and associate changes in gene expression with specific
      organismal phenotypes.

PMID- 17519967
TI  - Ecological genomics in Daphnia: stress responses and environmental sex
      determination.
AB  - Ecological genomics is the study of adaptation of natural populations to their
      environment, and therefore seeks to link organism and population level processes
      through an understanding of genome organization and function. The planktonic
      microcrustacean Daphnia, which has long been an important system for ecology, is
      now being used as a genomic model as well. Here we review recent progress in
      selected areas of Daphnia genomics research. Production of parthenogenetic male
      offspring occurs through environmental cues, which clearly involves endocrine
      regulation and has also been studied as a toxicological response to juvenoid
      hormone analog insecticides. Recent progress has uncovered a putative juvenoid
      cis-response element, which together with microarray analysis will stimulate
      further research into nuclear hormone receptors and their associated
      transcriptional regulatory networks. Ecotoxicological studies indicate that mRNA
      profiling is a sensitive and specific research tool with promising applications
      in environmental monitoring and for uncovering conserved cellular processes.
      Rapid progress is expected to continue in these and other areas, as genomic tools
      for Daphnia become widely available to investigators.

PMID- 17519968
TI  - Bidirectional incompatibility among divergent Wolbachia and incompatibility level
      differences among closely related Wolbachia in Nasonia.
AB  - Most insect groups harbor obligate bacterial symbionts from the alpha
      proteobacterial genus Wolbachia. These bacteria alter insect reproduction in ways
      that enhance their cytoplasmic transmission. One of the most common alterations
      is cytoplasmic incompatibility (CI) - a post-fertilization modification of the
      paternal genome that renders embryos inviable or unable to complete diploid
      development in crosses between infected males and uninfected females or infected
      females harboring a different strain. The parasitic wasp species complex Nasonia
      (N. vitripennis, N. longicornis and N. giraulti) harbor at least six different
      Wolbachia that cause CI. Each species have double infections with a
      representative from both the A and B Wolbachia subgroups. CI relationships of the
      A and B Wolbachia of N. longicornis with those of N. giraulti and N. vitripennis
      are investigated here. We demonstrate that all pairwise crosses between the
      divergent A strains are bidirectionally incompatible. We were unable to
      characterize incompatibility between the B Wolbachia, but we establish that the B
      strain of N. longicornis induces no or very weak CI in comparison to the closely
      related B strain in N. giraulti that expresses complete CI. Taken together with
      previous studies, we show that independent acquisition of divergent A Wolbachia
      has resulted in three mutually incompatible strains, whereas codivergence of B
      Wolbachia in N. longicornis and N. giraulti is associated with differences in CI
      level. Understanding the diversity and evolution of new incompatibility strains
      will contribute to a fuller understanding of Wolbachia invasion dynamics and
      Wolbachia-assisted speciation in certain groups of insects.

PMID- 17519969
TI  - Neutral versus adaptive genetic variation in parasite resistance: importance of
      major histocompatibility complex supertypes in a free-ranging primate.
AB  - Current discussions in evolutionary ecology and conservation genetics focus on
      the relative importance of using selective neutral markers or markers of coding
      genes to identify adaptive and evolutionary relevant processes. Genetic diversity
      might be particularly important in immune genes (e.g., in genes of the major
      histocompatibility complex, MHC), which are influencing pathogen and parasite
      resistance. We investigated the effects of neutral versus adaptive genetic
      variation in parasite resistance in a natural population of fat-tailed dwarf
      lemurs (Cheirogaleus medius). No association between neutral overall individual
      genetic diversity and parasite load could be detected. In 149 individuals, we
      identified 50 MHC class II alleles of the functionally important duplicated DRB
      locus. The investigation of the functional importance of immune gene (MHC)
      diversity and parasite selection in natural populations is often problematic due
      to extensive polymorphism in the MHC genes and restrictions in available sample
      sizes. Here, for the first time we applied an approach that has been developed in
      human medical studies. Eleven MHC class II supertypes were identified based on
      shared antigen-binding similarities. The number of individual MHC supertypes had
      no influence on the nematode burden. However, we found evidence for a specific
      MHC supertype (supertype 1) that was linked to infected individuals, a higher
      number of different nematode infections and high intensity of infection per
      individual. Moreover, one rare MHC supertype (supertype 7) was revealed to be
      advantageous with respect to parasite burden. Thus, our results add evidence to
      the small body of studies that show significant associations between specific MHC
      constitutions and naturally occurring parasites in the complexity of natural
      populations.

PMID- 17519970
TI  - Ecological genomics: understanding gene and genome function in the natural
      environment.
AB  - The field of ecological genomics seeks to understand the genetic mechanisms
      underlying responses of organisms to their natural environments. This is being
      achieved through the application of functional genomic approaches to identify and
      characterize genes with ecological and evolutionary relevance. By its very
      nature, ecological genomics is an interdisciplinary field. In this review, we
      consider the significance of this new area of study from both an ecological and
      genomic perspective using examples from the recent literature. We submit that by
      considering more fully an ecological context, researchers may gain additional
      insights into the underlying genetic basis of ecologically relevant phenotypic
      variation. Likewise, genomic approaches are beginning to offer new insights into
      higher-level biological phenomena that previously occupied the realm of
      ecological investigation only. We discuss various approaches that are likely to
      be useful in ecological genomic studies and offer thoughts on where this field is
      headed in the future.

PMID- 17519971
TI  - Non-neutral evolution of the major histocompatibility complex class II gene DRB1
      in the sac-winged bat Saccopteryx bilineata.
AB  - The immune genes of the major histocompatibility complex (MHC) are classical
      examples for high levels of genetic diversity and non-neutral evolution. This is
      particularly true for the regions containing the antigen-binding sites as, for
      instance, in the exon 2 of the MHC class II gene DRB. We surveyed, for the first
      time in the order Chiroptera, the genetic diversity within this exon in the sac
      winged bat Saccopteryx bilineata. We detected 11 alleles among 85 bats, of which
      79 were sampled in one population. Pairwise comparisons revealed that
      interallelic sequence differences ranged between 3 and 22%, although nucleotide
      substitutions were not evenly distributed along the exon sequence. This was most
      probably the result of intragenic recombination. High levels of sequence
      divergence and significantly more nonsynonymous than synonymous substitutions
      (d(N)/d(S)>1) suggest long-term balancing selection. Thus, the data are
      consistent with the hypothesis that recombination gives rise to new alleles at
      the DRB locus of the sac-winged bat, and these are maintained in the population
      through balancing selection. In this respect, the sac-winged bat closely
      resembles other mammalian species.

PMID- 17519972
TI  - Analysis of inbreeding depression in the first litter size of mice in a long-term
      selection experiment with respect to the age of the inbreeding.
AB  - An understanding of inbreeding and inbreeding depression are important in
      evolutionary biology, conservation genetics, and animal breeding. A new method
      was developed to detect departures from the classical model of inbreeding; in
      particular, it investigated differences between the effects of inbreeding in
      recent generations from that in the more distant past. The method was applied in
      a long-term selection experiment on first-litter size in mice. The total pedigree
      included 74,630 animals with approximately 30,000 phenotypic records. The
      experiment comprised several different lines. The highest inbreeding coefficients
      (F) within a line ranged from 0.22 to 0.64, and the average effective population
      size (N(e)) was 58.1. The analysis divided F into two parts, corresponding to the
      inbreeding occurring in recent generations ('new') and that which preceded it
      ('old'). The analysis was repeated for different definitions of 'old' and 'new',
      depending on length of the 'new' period. In 15 of these tests, 'new' inbreeding
      was estimated to cause greater depression than 'old'. The estimated depression
      ranged from -11.53 to -0.79 for the 'new' inbreeding and from -5.22 to 15.51 for
      'old'. The difference was significant, the 'new' period included at least 25
      generations of inbreeding. Since there were only small differences in N(e)
      between lines, and near constant N(e) within lines, the effect of 'new' and 'old'
      cannot be attributed to the effects of 'fast' versus 'slow' inbreeding. It was
      concluded that this departure from the classical model, which predicts no
      distinction between this 'old and 'new' inbreeding, must implicate natural
      selection and purging in influencing the magnitude of depression.

PMID- 17519973
TI  - Hypoxia-induced acute mountain sickness is associated with intracellular cerebral
      edema: a 3 T magnetic resonance imaging study.
AB  - Acute mountain sickness is common among not acclimatized persons ascending to
      high altitude; the underlying mechanism is unknown, but may be related to
      cerebral edema. Nine healthy male students were studied before and after 6-h
      exposure to isobaric hypoxia. Subjects inhaled room air enriched with N(2) to
      obtain arterial O(2) saturation values of 75 to 80%. Acute mountain sickness was
      assessed with the environmental symptom questionnaire, and cerebral edema with 3
      T magnetic resonance imaging in 18 regions of interest in the cerebral white
      matter. The main outcome measures were development of intra- and extracellular
      cerebral white matter edema assessed by visual inspection and quantitative
      analysis of apparent diffusion coefficients derived from diffusion-weighted
      imaging, and B0 signal intensities derived from T2-weighted imaging. Seven of
      nine subjects developed acute mountain sickness. Mean apparent diffusion
      coefficient increased 2.12% (baseline, 0.80+/-0.09; 6 h hypoxia, 0.81+/-0.09;
      P=0.034), and mean B0 signal intensity increased 4.56% (baseline, 432.1+/-98.2; 6
      h hypoxia, 450.7+/-102.5; P<0.001). Visual inspection of magnetic resonance
      images failed to reveal cerebral edema. Cerebral acute mountain sickness scores
      showed a negative correlation with relative changes of apparent diffusion
      coefficients (r=-0.83, P=0.006); there was no correlation with relative changes
      of B0 signal intensities. In conclusion, isobaric hypoxia is associated with mild
      extracellular (vasogenic) cerebral edema irrespective of the presence of acute
      mountain sickness in most subjects, and severe acute mountain sickness with
      additional mild intracellular (cytotoxic) cerebral edema.

PMID- 17519974
TI  - Interaction of mechanisms involving epoxyeicosatrienoic acids, adenosine
      receptors, and metabotropic glutamate receptors in neurovascular coupling in rat
      whisker barrel cortex.
AB  - Adenosine, astrocyte metabotropic glutamate receptors (mGluRs), and
      epoxyeicosatrienoic acids (EETs) have been implicated in neurovascular coupling.
      Although A(2A) and A(2B) receptors mediate cerebral vasodilation to adenosine,
      the role of each receptor in the cerebral blood flow (CBF) response to neural
      activation remains to be fully elucidated. In addition, adenosine can amplify
      astrocyte calcium, which may increase arachidonic acid metabolites such as EETs.
      The interaction of these pathways was investigated by determining if combined
      treatment with antagonists exerted an additive inhibitory effect on the CBF
      response. During whisker stimulation of anesthetized rats, the increase in
      cortical CBF was reduced by approximately half after individual administration of
      A(2B), mGluR and EET antagonists and EET synthesis inhibitors. Combining
      treatment of either a mGluR antagonist, an EET antagonist, or an EET synthesis
      inhibitor with an A(2B) receptor antagonist did not produce an additional
      decrement in the CBF response. Likewise, the CBF response also remained reduced
      by approximately 50% when an EET antagonist was combined with an mGluR antagonist
      or an mGluR antagonist plus an A(2B) receptor antagonist. In contrast, A(2A) and
      A(3) receptor antagonists had no effect on the CBF response to whisker
      stimulation. We conclude that (1) adenosine A(2B) receptors, rather than A(2A) or
      A(3) receptors, play a significant role in coupling cortical CBF to neuronal
      activity, and (2) the adenosine A(2B) receptor, mGluR, and EETs signaling
      pathways are not functionally additive, consistent with the possibility of
      astrocytic mGluR and adenosine A(2B) receptor linkage to the synthesis and
      release of vasodilatory EETs.

PMID- 17519975
TI  - Cerebral ischemia causes dysregulation of synaptic adhesion in mouse
      synaptosomes.
AB  - Synaptic pathology is observed during hypoxic events in the central nervous
      system in the form of altered dendrite structure and conductance changes. These
      alterations are rapidly reversible, on the return of normoxia, but are thought to
      initiate subsequent neuronal cell death. To characterize the effects of hypoxia
      on regulators of synaptic stability, we examined the temporal expression of cell
      adhesion molecules (CAMs) in synaptosomes after transient middle cerebral artery
      occlusion (MCAO) in mice. We focused on events preceding the onset of ischemic
      neuronal cell death (<48 h). Synaptosome preparations were enriched in
      synaptically localized proteins and were free of endoplasmic reticulum and
      nuclear contamination. Electron microscopy showed that the synaptosome
      preparation was enriched in spheres (approximately 650 nm in diameter) containing
      secretory vesicles and postsynaptic densities. Forebrain mRNA levels of
      synaptically located CAMs was unaffected at 3 h after MCAO. This is contrasted by
      the observation of consistent downregulation of synaptic CAMs at 20 h after MCAO.
      Examination of synaptosomal CAM protein content indicated that certain adhesion
      molecules were decreased as early as 3 h after MCAO. For comparison, synaptosomal
      Agrn protein levels were unaffected by cerebral ischemia. Furthermore, a marked
      increase in the levels of p-Ctnnb1 in ischemic synaptosomes was observed. p
      Ctnnb1 was detected in hippocampal fiber tracts and in cornu ammonis 1 neuronal
      nuclei. These results indicate that ischemia induces a dysregulation of a subset
      of synaptic proteins that are important regulators of synaptic plasticity before
      the onset of ischemic neuronal cell death.

PMID- 17519976
TI  - Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell
      angiogenesis in vitro.
AB  - Circulating blood endothelial progenitor cells (EPCs) contribute to postnatal
      vasculogenesis, providing a novel therapeutic target for vascular diseases.
      However, the molecular mechanism of EPC-induced vasculogenesis is unknown.
      Interleukin-6 plays multiple functions in angiogenesis and vascular remodeling.
      Our previous study demonstrated that the polymorphism (174G>C) in IL-6 gene
      promoter was associated with brain vascular disease. In this study, we
      investigated if IL-6 receptor is expressed in human EPCs derived from circulating
      mononuclear cells, and if interleukin-6 (IL-6) stimulates EPC angiogenesis in
      vitro. First, we isolated and cultured mononuclear cells from adult human
      circulating blood. We obtained EPC clones that were further cultured and expended
      for the angiogenesis study. We found that the EPCs possessed human mature
      endothelial cell phenotypes; however, they proliferated much faster than mature
      endothelial cells (P<0.05). We then found that IL-6 receptor (gp-80) was
      expressed in the EPCs, and that administration of IL-6 could activate receptor
      gp80/gp130 signaling pathways including downstream extracellular signal-regulated
      kinase 1/2 and STAT3 phosphorylation in EPCs. Furthermore, IL-6 stimulated EPC
      proliferation, migration, and matrigel tube formation in a dose-dependent manner
      (P<0.05); anti-IL-6 antibodies or IL-6 receptor could abolish these effects
      (P<0.05). These results suggest that IL-6 plays a crucial role in the biologic
      behavior of blood-derived EPCs, which may help clarify the mechanism of IL-6
      inflammatory-related diseases.

PMID- 17519977
TI  - Validation of cerebral venous oxygenation measured using near-infrared
      spectroscopy and partial jugular venous occlusion in the newborn lamb.
AB  - Near-infrared spectroscopy combined with partial jugular venous occlusion (JVO)
      offers promise for determining cerebral venous saturation (CSvO(2)) in sick
      preterm infants, but has not been validated in the newborn brain or under
      conditions of hypoxaemia. We assessed the accuracy of the CSvO(2) estimate using
      cerebral venous oxygen saturation in superior sagittal sinus blood (SSSO(2)) as
      the 'gold standard'. Comparisons were made in seven newborn lambs over a wide
      range of arterial oxygen saturations (SaO(2)) of 20% to 100%. Overall, median
      (range) CSvO(2) was 49.8% (10.6% to 88.5%), whereas SSSO(2) was 45.5% (4.3% to
      76.6%); Bland-Altman analysis revealed a mean difference (CSvO(2)-SSSO(2)) of
      5.1% and limits of agreement of +/-27.4%. The change in cerebral blood volume
      (DeltaCBV) induced by JVO increased with SaO(2) (P<0.05). In addition, the
      strength of the correlation of CSvO(2) with SSSO(2) progressively improved with
      increasing change in total haemoglobin concentration (DeltaHbT) induced by JVO.
      With Bland-Altman analysis repeated for data with DeltaHbT >30 micromol cm, the
      mean difference (CSvO(2)-SSSO(2)) decreased to 2.4% with limits of agreement of
      +/-18.8%. We conclude that the accuracy of estimating CSvO(2) varies with the
      DeltaCBV induced by JVO. Potential differences of optical properties between the
      head of the lamb and the human infant suggest that caution be exercised in
      directly applying these data to the human newborn. Nevertheless, this critical
      aspect of the JVO technique needs to be taken into consideration in developing an
      accurate measurement for sick preterm human infants.

PMID- 17519978
TI  - Quantification of cerebral nicotinic acetylcholine receptors by PET using 2
      [18F]fluoro-A-85380 and the multiinjection approach.
AB  - The multiinjection approach was used to study in vivo interactions between
      alpha4beta2(*) nicotinic acetylcholine receptors and 2-[(18)F]fluoro-A-85380 in
      baboons. The ligand kinetics was modeled by the usual nonlinear compartment model
      composed of three compartments (arterial plasma, free and specifically bound
      ligand in tissue). Arterial blood samples were collected to generate a metabolite
      corrected plasma input function. The experimental protocol, which consisted of
      three injections of labeled or unlabeled ligand, was aiming at identifying all
      parameters in one experiment. Various parameters, including B'(max) (the binding
      sites density) and K(d)V(R) (the apparent in vivo affinity of 2-[(18)F]fluoro-A
      85380) could then be estimated in thalamus and in several receptor-poor regions.
      B'(max) estimate was 3.0+/-0.3 pmol/mL in thalamus, and ranged from 0.25 to 1.58
      pmol/mL in extrathalamic regions. Although K(d)V(R) could be precisely estimated,
      the association and dissociation rate constants k(on)/V(R) and k(off) could not
      be identified separately. A second protocol was then used to estimate k(off) more
      precisely in the thalamus. Having estimated all model parameters, we performed
      simulations of 2-[(18)F]fluoro-A-85380 kinetics to test equilibrium hypotheses
      underlying simplified approaches. These showed that a pseudo-equilibrium is
      quickly reached between the free and bound compartments, a favorable situation to
      apply Logan graphical analysis. In contrast, the pseudo-equilibrium between the
      plasma and free compartments is only reached after several hours. The ratio of
      radioligand concentration in these two compartments then overestimates the true
      equilibrium value, an unfavorable situation to estimate distribution volumes from
      late images after a bolus injection.

PMID- 17519980
TI  - [Dream vaccine or still a dream?].

PMID- 17519979
TI  - Consensus nomenclature for in vivo imaging of reversibly binding radioligands.
AB  - An international group of experts in pharmacokinetic modeling recommends a
      consensus nomenclature to describe in vivo molecular imaging of reversibly
      binding radioligands.

PMID- 17519981
TI  - [Guidelines--by whom and for whom?].

PMID- 17519982
TI  - [Quality registry for better stroke treatment].

PMID- 17519983
TI  - [Future of out-of-hours primary health care services].

PMID- 17519984
TI  - [Organization of Norwegian out-of-hours primary health care services].
AB  - BACKGROUND: The organization of out-of-hours primary health care services in
      Norway is currently changing from municipal-based to larger inter-municipal co
      operations with regular employees and improved competence. The Norwegian Medical
      Association and others have encouraged the establishment of larger out-of-hours
      primary health care units that include all municipalities and regular GPs and
      serve the entire population. More data are needed to study the situation for out
      of-hours services in Norway. MATERIAL AND METHODS: The National Centre for
      Emergency Primary Health Care sent questionnaires to all 433 municipalities in
      Norway the autumn of 2005 to study how the out-of-hours primary health services
      are organized. RESULTS: Out-of-hours primary health services is an inter
      municipality endeavour in two-thirds of Norwegian municipalities and one third of
      the remaining municipalities have plans to start such co-operation. Regular GPs
      participate in out-of-hours services to a varying degree. In half of the
      municipalities all regular GPs participate in out-of-hours duty. Participation
      decreases with increasing numbers of inhabitants and regular GPs in the
      municalities. We found a distinct variation in the number of phone calls per
      inhabitant to municipal out-of-hours services. Due to geographical factors, there
      are also variations in patient transport time and availability of ambulances to
      the out-of-hours offices. INTERPRETATION: We observed distinct variations in the
      organization of the out-of-hours emergency primary health services in Norway.
      Some of these differences are due to differences in population density and
      geographical factors.

PMID- 17519985
TI  - [Locations, facilities and routines in Norwegian out-of-hours emergency primary
      health care services].
AB  - BACKGROUND: Limited data are available on casualty clinic facilities and
      localisation, inter-municipal co-operation and routines for out-of-hours services
      in the 433 Norwegian municipalities. The National centre for emergency primary
      health care collected data on these issues from October 2005 until February 2006.
      METHOD: Questionnaires concerning organisation of the out-of-hours services,
      casualty clinic facilities, locations and routines were sent to every Norwegian
      municipality. RESULTS: 282 of the 433 municipalities are in charge of out-of
      hours services in 262 districts in the evenings and 230 districts during nights
      and weekends. There is inter-municipal cooperation in 100 of the districts. Most
      out-of-hours services are located in one casualty clinic in the host municipality
      and have the same locations as GP surgeries and laboratories. Most clinics
      offered the same services, but some routines were different. About half of the
      casualty clinics had a system for training of doctors and other health personnel.
      Half of the doctors on duty were available on the emergency communications system
      (radio). User assessments were collected, telephone calls documented and
      discrepancies reported to a varying degree, and medical histories were not
      consistently sent to regular GPs. INTERPRETATION: Inter-municipal co-operations
      are most common in areas with a high population density, i.e. in southern and
      eastern parts of Norway. Varying routines in out-of-hours service districts
      indicate that several municipalities do not fulfil all the obligations in
      regulations from the Ministry of health and care services in Norway.

PMID- 17519986
TI  - [Differences in requests to out-of-hours services].
AB  - BACKGROUND: Out-of-hours services in Norway have not been systematically assessed
      and no national statistics exist. This article reports a pilot study of requests
      to three casualty clinics and the activities related to these requests. MATERIAL
      AND METHODS: All requests to the three clinics, day and night for four weeks in
      the spring of 2006, were recorded. Variables and definitions were discussed with
      all participating personnel before start. A coordinator at each casualty clinic
      was responsible for ensuring data quality and sending data to the study centre
      weekly. RESULTS: 5,041 requests were recorded. Contact rates per 1,000
      inhabitants ranged from 29 to 84. In two casualty clinics a large majority of the
      contacts were given the priority grade "not urgent". In one casualty clinic the
      rate "acute" was more than twice the rate in the two others. The rate of
      consultation with GPs differed, but the rate of home visits and acute response by
      ambulance and GP was low in all the casualty clinics. INTERPRETATION: Large
      differences were identified regarding several factors affecting requests to
      casualty clinics in Norway. This pilot study supports the need for a larger and
      more representative study.

PMID- 17519987
TI  - [Which physicians receive reimbursement for out-of-hours work?].
AB  - BACKGROUND: Norwegian regular general practitioners (RGPs) are required to
      participate in out-of-hours duty. The aim of this study was to determine their
      actual participation rate. MATERIAL AND METHODS: Information was collected from
      the RGP Database, the Municipality Database and from physicians' bills to the
      National Insurance in 2004. The material consists of 3,751 RGPs and 2,317 other
      physicians claiming reimbursement for out-of-hours work. RESULTS: RGPs received
      51.8% of the total reimbursement for out-of-hours work, and 35.6% of them did not
      have any such income. Male RGPs received almost twice as much reimbursement for
      out-of-hours duty as their female colleagues, and there was a strong tendency for
      older RGPs to receive less. Among all physicians, young men were those who
      generally worked most frequently out-of-hours. RGPs' reimbursement dropped with
      poorer coverage of doctors, increasing list size, if their list was full or
      overcrowded, and with increasing size and central localization of the
      municipality. INTERPRETATION: A large proportion of RGPs do not work out-of-hours
      in emergency services.

PMID- 17519988
TI  - [Fewer regular general practitioners participate in out-of-hours emergency
      services].
AB  - BACKGROUND: The aim of the study was to determine whether the official numbers of
      regular general practitioners (GPs) participating in out-of-hours duty have been
      correct. METHOD: Data were collected from the Norwegian labour and welfare
      organisation's (NAV's) regular GP database. This is a database with information
      collected from Statistics Norway and the Norwegian Social Science Data Services.
      RESULTS: The study has revealed an error in one of the sources used by the
      national health authorities to evaluate the regular GP Scheme
      "Fastlegeordningen". Official figures indicate that the number of regular GPs who
      participate in out-of-hours duty increased with 5% the first three years after
      implementation of the regular GP Scheme (2001-2004). New analyses show that the
      number of regular GPs instead decreased with 12%. INTERPRETATION: Our study
      uncovers weaknesses with the quality assurance of data used by the health
      authorities to calculate the work force needed for out-of-hours duty. This
      misinformation may have prevented action needed to recruit regular GPs to work in
      the out-of-hours emergency services, as the problem has not been recognised.

PMID- 17519989
TI  - [Arthroscopic capsular release in treatment of primary frozen shoulder].
AB  - BACKGROUND: Frozen shoulder is a debilitating, long-lasting condition. At Bergen
      Surgical Hospital we have performed arthroscopic capsular release since 2003 in
      patients where conservative treatment has failed. The procedure is done as day
      surgery. The purpose of this study was to evaluate our results. PATIENTS AND
      METHODS: From June 2003 until October 2005 arthroscopic capsular and ligament
      release was performed in 66 patients (70 shoulders) with primary frozen shoulder.
      Oxford shoulder score and range of motion were recorded prospectively. Follow-up
      was done during autumn 2005 and included subjective evaluation of symptoms,
      function, satisfaction with the result of the procedure, Oxford shoulder score
      and clinical examination. RESULTS: 62 out of 66 patients would agree to have the
      same procedure done again. Degree of satisfaction with the result of the
      procedure (0 = worst, 10 = best) was 8.6 +/- 1.8 (SD) on average. Ability to
      work, physical activity and quality of night's sleep improved significantly (p <
      0.001). Oxford shoulder score (12 = best, 60 = worst) decreased significantly
      from 41.0 +/- 7.5 (SD) to 18.4 +/- 7.3 (SD) (p < 0.001). External rotation,
      abduction and flexion increased significantly (p < 0.001). INTERPRETATION: The
      results from treatment of frozen shoulder with arthroscopic capsular release are
      good and suggest that the the condition shoulder is shortened. The procedure may
      be done safely as day surgery. We feel that more patients may benefit from the
      procedure.

PMID- 17519990
TI  - [Sleep deprivation as antidepressive treatment].
AB  - BACKGROUND: Sleep deprivation, i.e. keeping patients awake for approximately 35
      hours, is an antidepressive treatment that is rarely used in Norway. MATERIAL AND
      METHODS: Review of a selection of publications from Medline, ISI, and psychINFO.
      The treatment is illustrated with two clinical vignettes. RESULTS AND
      INTERPRETATION: Sleep deprivation is a well documented treatment of depression.
      The effect is transient but can be prolonged by sleep phase advancement,
      concurrent pharmacological treatment, and light therapy. The effect is comparable
      to other standard treatments for depression, but is reported to occur within
      hours rather than weeks. There are few studies with follow-up results for more
      than two weeks and there is uncertainty regarding the mechanisms of change that
      are involved in sleep deprivation. Our two pilot patients experienced over 50%
      symptom reduction in three days. Results from these patients indicate that it may
      be of interest to study the course of response to sleep deprivation and three day
      sleep phase advancement for several weeks, and whether the treatment has the
      additional effect of improving sleep quality and stabilizing diurnal rhythm.

PMID- 17519991
TI  - [Training after percutaneous coronary intervention- an undervalued treatment
      option?].
AB  - BACKGROUND: Even though regular exercise training after myocardial infarction
      reduces morbidity and mortality, training after percutaneous coronary
      intervention (PCI) is still not part of the standard treatment. This article
      reviews the documentation on exercise training with coronary artery disease and
      examines the effect on pathophysiological mechanisms that play an important role
      in the progression of coronary artery disease and restenosis after PCI with stent
      implantation. MATERIAL AND METHODS: The article is based on a search in PubMed
      and the Cochcrane database. RESULTS AND INTERPRETATION: The effect of regular
      exercise training on morbitity and mortality in coronary artery disease without
      myocardial infarction is not well documented. But the data indicate that training
      has an antiinflammatory effect in the vessel wall. Regular exercise training in
      these patients increases the bioavailibility of nitric oxide and is a non
      pharmacological option to improve the endothelial function. Prospective,
      randomised, controlled trials are needed to evaluate whether there is a
      beneficial clinical effect of training after PCI treatment.

PMID- 17519992
TI  - [Guidelines on do-not-resuscitate orders in Norwegian hospitals].
AB  - BACKGROUND: All somatic hospitals in Norway should have guidelines on do-not
      resuscitate orders, according to a directive issued by the Norwegian Board of
      Health in 2002. MATERIAL AND METHODS: All 31 Norwegian hospital trusts were asked
      to send in such guidelines. 20 submitted guidelines were assessed, analysed and
      compared according to 19 questions. RESULTS: The guidelines have various
      contents. Key aspects such as indications, definitions, participation in decision
      making by patients and relatives, strategies for conflict resolution, competence
      to consent, and advanced directives are in many guidelines either not commented,
      or described in an ambiguous manner. There are minor differences between the
      guidelines developed before and after the legal directive was issued in 2002, but
      legal provisions have become more heavily emphasized. INTERPRETATION: National
      guidelines should be developed to clarify key questions and contribute to more
      consistent practice concerning do-not-resuscitate orders.

PMID- 17519993
TI  - [Stroke--a study of clinical management and prognosis].
AB  - BACKGROUND: Knowledge on how to treat stroke effectively is increasing, but is
      not always implemented into clinical practice. The aim of this study was to
      establish the treatment offered, clinical status at discharge and long-term
      results for stroke patients admitted to a Norwegian local hospital. MATERIAL AND
      METHODS: 421 patients were treated for stroke at Baerum hospital during the years
      1994-1995. Patient history, medication, radiological findings and clinical
      findings at admission and discharge were recorded in a local register. Data on
      survival and re-hospitalisation for recurrent stroke were recorded for a period 7
      to 9 years after discharge, i.e. until January 2003. RESULTS: Hospital mortality
      was 17%. 49% were discharged directly to their homes. No antihypertensive
      treatment was given to 106 (51.6%) of the 206 patients who had hypertension upon
      discharge. 273 (90%) of the 303 patients discharged after cerebral infarction,
      were receiving antithrombotic treatment with warfarin or acetylic salicylic acid
      upon discharge. The most important prognostic factor for survival and functional
      ability was the patient's age at the time of stroke and next, the stroke's
      anatomical localization and extent. INTERPRETATION: Registers for follow-up of
      stroke patients provide valuable information on clinical practice and can form a
      basis for improved treatment of stroke in the future.

PMID- 17519994
TI  - [Secondary prophylaxis after ischemic stroke and transitoric ischemic attack].
AB  - BACKGROUND: Approximately 13,000 persons develop a stroke in Norway each year.
      3,000 of these are recurrent strokes. There are also more than 10,000 patients
      who experience a transitory ischemic attack each year which often immediately
      precedes a stroke. The aim of this review article is to present updated treatment
      recommendations for secondary prophylaxis after an ischemic stroke or TIA.
      MATERIAL AND METHODS: This article is based on the guidelines from the European
      Stroke Initiative, the American Stroke Association and review articles found by
      searching Medline and the Cochrane database. New relevant randomized studies are
      also included and discussed. Therapy guidelines have been modified for Norwegian
      use. RESULTS AND INTERPRETATION: Individualised secondary prophylaxis following
      an ischemic stroke or TIA can prevent cerebrovascular disease and death. It is
      especially important with optimal blood pressure and blood glucose control as
      well as adequate antithrombotic and lipid-lowering treatment.

PMID- 17519995
TI  - [Incontinence after stroke].
AB  - BACKGROUND: Urinary and fecal incontinence can be a consequence of cerebral
      stroke. This article aims to give an overview of incidence, prevalence, risk
      factors, natural course and management of stroke-related incontinence. METHODS:
      MEDLINE search in relevant literature during the last 15 years, and own clinical
      and research experience. RESULTS AND CONCLUSIONS: Stroke-related incontinence is
      a frequent and bothersome symptom and a sign of a bad prognosis. Despite a
      certain spontaneous remission rate during the first year after onset of stroke, a
      considerable number of patients will have chronic problems. Many factors affect
      bladder and bowel function, and several of them are often present in the same
      individual. Keeping a record of natural functions and knowledge of incontinence
      is a prerequisite for all treatment. Impaired central inhibition of the
      micturition reflex is one important cause of urinary incontinence. Failure of
      certain cognitive functions probably has the greatest negative impact on
      prognosis. Even though established therapies for some urinary incontinence types
      have not been tested specifically in stroke patients, they may have effect and
      should be tried. Very little is known about post-stroke fecal incontinence.
      Patients with pre-existing incontinence should be offered help if they have not
      yet had a proper assessment and if they are motivated for it. There is a
      considerable need for further research in the field.

PMID- 17519996
TI  - [Depression, anxiety and other emotional symptoms after cerebral stroke].
AB  - BACKGROUND: Emotional symptoms are probably among the most ignored impairments in
      stroke patients. Of these, depression is best described, and appears in 20-40% of
      the stroke patients. Other emotional symptoms are anxiety (20-30%), emotional
      instability (10-25%), crisis reaction (20%) and reduced initiative and fatigue
      (50-70%). Depression and anxiety are, according to some publications, related to
      organic lesions in the anterior parts of the left hemisphere, although this
      relationship is under discussion. In addition, marital status and neurological
      impairments correlate with emotional symptoms in stroke. MATERIAL AND METHODS:
      The manuscript is based on a Medline search (1980-2006) and on own clinical
      experience and research. RESULTS AND INTERPRETATION: Several diagnostic
      instruments are in use to identify emotional symptoms in patients who suffer from
      stroke. Of these, the Montgomery-Asberg-Depression-Rating-Scale, the Geriatric
      Depression Scale and the Hospital Anxiety and Depression Scale are the most
      frequently used to diagnose post-stroke anxiety and depression in Norway. Aphasia
      and other cognitive impairments do however make these instruments difficult to
      use. At present, pharmacological treatment consists of selective serotonine
      reuptake inhibitors and serotonine noradrenaline reuptake inhibitors. Tricyclic
      antidepressive therapy is also effective, but often unsuitable due to side
      effects. Post-stroke emotional symptoms may affect the patients' neurological
      outcome, and should be emphasized more in the stroke unit. Documentation is
      insufficient regarding the effects of medical intervention, and more knowledge is
      needed.

PMID- 17519997
TI  - [Cognitive impairment after stroke--diagnosis and management].
AB  - BACKGROUND: An incidence of stroke is often followed by cognitive impairment.
      This review article presents an update about such impairment and emphasises
      diagnostical and therapeutical challenges. MATERIAL AND METHOD: This article is
      based mainly on literature identified on Medline using the terms "cognitive
      impairment and stroke," "dementia and stroke," "vascular dementia" and "vascular
      cognitive impairment." RESULTS AND INTERPRETATION: Cognitive impairment after
      stroke varies with respect to cerebral localisation and the magnitude of injured
      brain tissue, and may be classified according to neuropsychological profile and
      neuroanatomical damage. The cognitive domains affected are in particular
      executive functions, motor and psychomotor abilities (mapped by speeded tests)
      and attention. Executive function comprises planning, organising, conducting,
      assessing and controlling actions. The neuropathological basis for these
      cognitive domains is mainly located in frontal subcortical brain areas. Cognitive
      impairment can be identified using neuropsychological tests as verbal fluency
      (FAS) corresponding to executive function, digit span (psychomotor abilities) and
      finger-tapping (motor speed). The Mini Mental State Examination test is of
      limited diagnostic help, but is recommended due to the need of a global cognitive
      functioning measure. The treatment recommended comprises sound measures for
      secondary prevention of stroke directed towards vascular risk factors. Non
      pharmaceutical intervention such as physical training, cognitive and social
      stimulation probably has a greater therapeutic potential than normally assumed.

PMID- 17519998
TI  - [Insufficient view of ethical guidelines].

PMID- 17519999
TI  - [Somadril recalled in Norway].

PMID- 17520000
TI  - [Arguments to a senior policy].

PMID- 17520001
TI  - [Misleading about substance abuse in schools].

PMID- 17520003
TI  - [Substance abuse can cause stroke].

PMID- 17520005
TI  - [The brain belongs to all].

PMID- 17520006
TI  - [Suprapubic bladder drainage after abdominal surgery in Norway].

PMID- 17520012
TI  - The Arabidopsis thaliana brassinosteroid receptor (AtBRI1) contains a domain that
      functions as a guanylyl cyclase in vitro.
AB  - BACKGROUND: Guanylyl cyclases (GCs) catalyze the formation of the second
      messenger guanosine 3',5'-cyclic monophosphate (cGMP) from guanosine 5'
      triphosphate (GTP). Cyclic GMP has been implicated in an increasing number of
      plant processes, including responses to abiotic stresses such as dehydration and
      salt, as well as hormones. PRINCIPLE FINDINGS: Here we used a rational search
      strategy based on conserved and functionally assigned residues in the catalytic
      centre of annotated GCs to identify candidate GCs in Arabidopsis thaliana and
      show that one of the candidates is the brassinosteroid receptor AtBR1, a leucine
      rich repeat receptor like kinase. We have cloned and expressed a 114 amino acid
      recombinant protein (AtBR1-GC) that harbours the putative catalytic domain, and
      demonstrate that this molecule can convert GTP to cGMP in vitro. CONCLUSIONS: Our
      results suggest that AtBR1 may belong to a novel class of GCs that contains both
      a cytosolic kinase and GC domain, and thus have a domain organisation that is not
      dissimilar to that of atrial natriuretic peptide receptors, NPR1 and NPR2. The
      findings also suggest that cGMP may have a role as a second messenger in
      brassinosteroid signalling. In addition, it is conceivable that other proteins
      containing the extended GC search motif may also have catalytic activity, thus
      implying that a significant number of GCs, both in plants and animals, remain to
      be discovered, and this is in keeping with the fact that the single cellular
      green alga Chlamydomonas reinhardtii contains over 90 annotated putative CGs.

PMID- 17520013
TI  - Molecular biogeography: towards an integrated framework for conserving pan
      African biodiversity.
AB  - BACKGROUND: Biogeographic models partition ecologically similar species
      assemblages into discrete ecoregions. However, the history, relationship and
      interactions between these regions and their assemblages have rarely been
      explored. METHODOLOGY/PRINCIPAL FINDINGS: Here we develop a taxon-based approach
      that explicitly utilises molecular information to compare ecoregion history and
      status, which we exemplify using a continentally distributed mammalian species:
      the African bushbuck (Tragelaphus scriptus). We reveal unprecedented levels of
      genetic diversity and structure in this species and show that ecoregion
      biogeographic history better explains the distribution of molecular variation
      than phenotypic similarity or geography. We extend these data to explore
      ecoregion connectivity, identify core habitats and infer ecological affinities
      from them. CONCLUSIONS/SIGNIFICANCE: This analysis defines 28 key biogeographic
      regions for sub-Saharan Africa, and provides a valuable framework for the
      incorporation of genetic and biogeographic information into a more widely
      applicable model for the conservation of continental biodiversity.

PMID- 17520014
TI  - Absent or low rate of adult neurogenesis in the hippocampus of bats (Chiroptera).
AB  - Bats are the only flying mammals and have well developed navigation abilities for
      3D-space. Even bats with comparatively small home ranges cover much larger
      territories than rodents, and long-distance migration by some species is unique
      among small mammals. Adult proliferation of neurons, i.e., adult neurogenesis, in
      the dentate gyrus of rodents is thought to play an important role in spatial
      memory and learning, as indicated by lesion studies and recordings of neurons
      active during spatial behavior. Assuming a role of adult neurogenesis in
      hippocampal function, one might expect high levels of adult neurogenesis in bats,
      particularly among fruit- and nectar-eating bats in need of excellent spatial
      working memory. The dentate gyrus of 12 tropical bat species was examined
      immunohistochemically, using multiple antibodies against proteins specific for
      proliferating cells (Ki-67, MCM2), and migrating and differentiating neurons
      (Doublecortin, NeuroD). Our data show a complete lack of hippocampal neurogenesis
      in nine of the species (Glossophaga soricina, Carollia perspicillata,
      Phyllostomus discolor, Nycteris macrotis, Nycteris thebaica, Hipposideros
      cyclops, Neoromicia rendalli, Pipistrellus guineensis, and Scotophilus
      leucogaster), while it was present at low levels in three species (Chaerephon
      pumila, Mops condylurus and Hipposideros caffer). Although not all antigens were
      recognized in all species, proliferation activity in the subventricular zone and
      rostral migratory stream was found in all species, confirming the appropriateness
      of our methods for detecting neurogenesis. The small variation of adult
      hippocampal neurogenesis within our sample of bats showed no indication of a
      correlation with phylogenetic relationship, foraging strategy, type of hunting
      habitat or diet. Our data indicate that the widely accepted notion of adult
      neurogenesis supporting spatial abilities needs to be considered carefully. Given
      their astonishing longevity, certain bat species may be useful subjects to
      compare adult neurogenesis with other long-living species, such as monkeys and
      humans, showing low rates of adult hippocampal neurogenesis.

PMID- 17520015
TI  - High-yield hydrogen production from starch and water by a synthetic enzymatic
      pathway.
AB  - BACKGROUND: The future hydrogen economy offers a compelling energy vision, but
      there are four main obstacles: hydrogen production, storage, and distribution, as
      well as fuel cells. Hydrogen production from inexpensive abundant renewable
      biomass can produce cheaper hydrogen, decrease reliance on fossil fuels, and
      achieve zero net greenhouse gas emissions, but current chemical and biological
      means suffer from low hydrogen yields and/or severe reaction conditions.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate a synthetic enzymatic pathway
      consisting of 13 enzymes for producing hydrogen from starch and water. The
      stoichiometric reaction is C(6)H(10)O(5) (l)+7 H(2)O (l)-->12 H(2) (g)+6 CO(2)
      (g). The overall process is spontaneous and unidirectional because of a negative
      Gibbs free energy and separation of the gaseous products with the aqueous
      reactants. CONCLUSIONS: Enzymatic hydrogen production from starch and water
      mediated by 13 enzymes occurred at 30 degrees C as expected, and the hydrogen
      yields were much higher than the theoretical limit (4 H(2)/glucose) of anaerobic
      fermentations. SIGNIFICANCE: The unique features, such as mild reaction
      conditions (30 degrees C and atmospheric pressure), high hydrogen yields, likely
      low production costs ($ approximately 2/kg H(2)), and a high energy-density
      carrier starch (14.8 H(2)-based mass%), provide great potential for mobile
      applications. With technology improvements and integration with fuel cells, this
      technology also solves the challenges associated with hydrogen storage,
      distribution, and infrastructure in the hydrogen economy.

PMID- 17520016
TI  - Ionizing radiation changes the electronic properties of melanin and enhances the
      growth of melanized fungi.
AB  - BACKGROUND: Melanin pigments are ubiquitous in nature. Melanized microorganisms
      are often the dominating species in certain extreme environments, such as soils
      contaminated with radionuclides, suggesting that the presence of melanin is
      beneficial in their life cycle. We hypothesized that ionizing radiation could
      change the electronic properties of melanin and might enhance the growth of
      melanized microorganisms. METHODOLOGY/PRINCIPAL FINDINGS: Ionizing irradiation
      changed the electron spin resonance (ESR) signal of melanin, consistent with
      changes in electronic structure. Irradiated melanin manifested a 4-fold increase
      in its capacity to reduce NADH relative to non-irradiated melanin. HPLC analysis
      of melanin from fungi grown on different substrates revealed chemical complexity,
      dependence of melanin composition on the growth substrate and possible influence
      of melanin composition on its interaction with ionizing radiation. XTT/MTT assays
      showed increased metabolic activity of melanized C. neoformans cells relative to
      non-melanized cells, and exposure to ionizing radiation enhanced the electron
      transfer properties of melanin in melanized cells. Melanized Wangiella
      dermatitidis and Cryptococcus neoformans cells exposed to ionizing radiation
      approximately 500 times higher than background grew significantly faster as
      indicated by higher CFUs, more dry weight biomass and 3-fold greater
      incorporation of (14)C-acetate than non-irradiated melanized cells or irradiated
      albino mutants. In addition, radiation enhanced the growth of melanized
      Cladosporium sphaerospermum cells under limited nutrients conditions.
      CONCLUSIONS/SIGNIFICANCE: Exposure of melanin to ionizing radiation, and possibly
      other forms of electromagnetic radiation, changes its electronic properties.
      Melanized fungal cells manifested increased growth relative to non-melanized
      cells after exposure to ionizing radiation, raising intriguing questions about a
      potential role for melanin in energy capture and utilization.

PMID- 17520017
TI  - Impact of HIV on cell survival and antiviral activity of plasmacytoid dendritic
      cells.
AB  - Plasmacytoid dendritic cells (pDCs) are important mediators of innate immunity
      that act mainly through secretion of interferon (IFN)-alpha. Previous studies
      have found that these cells can suppress HIV in vitro; additionally, pDCs have
      been shown to be severely reduced in the peripheral blood of HIV-infected
      individuals. In the present study, we sought to determine the ability of pDCs to
      directly suppress viral replication ex vivo and to delineate the potential
      mechanisms whereby pDCs are depleted in HIV-infected individuals. We demonstrate
      that activated pDCs strongly suppress HIV replication in autologous CD4(+) T
      cells via a mechanism involving IFN-alpha as well as other antiviral factors. Of
      note, unstimulated pDCs from infected individuals who maintain low levels of
      plasma viremia without antiretroviral therapy were able to suppress HIV ex vivo
      via a mechanism requiring cell-to-cell contact. Our data also demonstrate that
      death of pDCs by both apoptosis and necrosis is induced by fusion of HIV with
      pDCs. Taken together, our data suggest that pDCs play an important role in the
      control of HIV replication and that high levels of viral replication in vivo are
      associated with pDC cell death via apoptosis and necrosis. Elucidation of the
      mechanism by which pDCs suppress HIV replication in vivo may have clinically
      relevant implications for future therapeutic strategies.

PMID- 17520018
TI  - Analysis of intraviral protein-protein interactions of the SARS coronavirus
      ORFeome.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted
      to encode 14 functional open reading frames, leading to the expression of up to
      30 structural and non-structural protein products. The functions of a large
      number of viral ORFs are poorly understood or unknown. In order to gain more
      insight into functions and modes of action and interaction of the different
      proteins, we cloned the viral ORFeome and performed a genome-wide analysis for
      intraviral protein interactions and for intracellular localization. 900 pairwise
      interactions were tested by yeast-two-hybrid matrix analysis, and more than 65
      positive non-redundant interactions, including six self interactions, were
      identified. About 38% of interactions were subsequently confirmed by CoIP in
      mammalian cells. Nsp2, nsp8 and ORF9b showed a wide range of interactions with
      other viral proteins. Nsp8 interacts with replicase proteins nsp2, nsp5, nsp6,
      nsp7, nsp8, nsp9, nsp12, nsp13 and nsp14, indicating a crucial role as a major
      player within the replication complex machinery. It was shown by others that nsp8
      is essential for viral replication in vitro, whereas nsp2 is not. We show that
      also accessory protein ORF9b does not play a pivotal role for viral replication,
      as it can be deleted from the virus displaying normal plaque sizes and growth
      characteristics in Vero cells. However, it can be expected to be important for
      the virus-host interplay and for pathogenicity, due to its large number of
      interactions, by enhancing the global stability of the SARS proteome network, or
      play some unrealized role in regulating protein-protein interactions. The
      interactions identified provide valuable material for future studies.

PMID- 17520019
TI  - Virtual Northern analysis of the human genome.
AB  - BACKGROUND: We applied the Virtual Northern technique to human brain mRNA to
      systematically measure human mRNA transcript lengths on a genome-wide scale.
      METHODOLOGY/PRINCIPAL FINDINGS: We used separation by gel electrophoresis
      followed by hybridization to cDNA microarrays to measure 8,774 mRNA transcript
      lengths representing at least 6,238 genes at high (>90%) confidence. By comparing
      these transcript lengths to the Refseq and H-Invitational full-length cDNA
      databases, we found that nearly half of our measurements appeared to represent
      novel transcript variants. Comparison of length measurements determined by
      hybridization to different cDNAs derived from the same gene identified clones
      that potentially correspond to alternative transcript variants. We observed a
      close linear relationship between ORF and mRNA lengths in human mRNAs, identical
      in form to the relationship we had previously identified in yeast. Some
      functional classes of protein are encoded by mRNAs whose untranslated regions
      (UTRs) tend to be longer or shorter than average; these functional classes were
      similar in both human and yeast. CONCLUSIONS/SIGNIFICANCE: Human transcript
      diversity is extensive and largely unannotated. Our length dataset can be used as
      a new criterion for judging the completeness of cDNAs and annotating mRNA
      sequences. Similar relationships between the lengths of the UTRs in human and
      yeast mRNAs and the functions of the proteins they encode suggest that UTR
      sequences serve an important regulatory role among eukaryotes.

PMID- 17520020
TI  - Global genetic population structure of Bacillus anthracis.
AB  - Anthrax, caused by the bacterium Bacillus anthracis, is a disease of historical
      and current importance that is found throughout the world. The basis of its
      historical transmission is anecdotal and its true global population structure has
      remained largely cryptic. Seven diverse B. anthracis strains were whole-genome
      sequenced to identify rare single nucleotide polymorphisms (SNPs), followed by
      phylogenetic reconstruction of these characters onto an evolutionary model. This
      analysis identified SNPs that define the major clonal lineages within the
      species. These SNPs, in concert with 15 variable number tandem repeat (VNTR)
      markers, were used to subtype a collection of 1,033 B. anthracis isolates from 42
      countries to create an extensive genotype data set. These analyses subdivided the
      isolates into three previously recognized major lineages (A, B, and C), with
      further subdivision into 12 clonal sub-lineages or sub-groups and, finally, 221
      unique MLVA15 genotypes. This rare genomic variation was used to document the
      evolutionary progression of B. anthracis and to establish global patterns of
      diversity. Isolates in the A lineage are widely dispersed globally, whereas the B
      and C lineages occur on more restricted spatial scales. Molecular clock models
      based upon genome-wide synonymous substitutions indicate there was a massive
      radiation of the A lineage that occurred in the mid-Holocene (3,064-6,127 ybp).
      On more recent temporal scales, the global population structure of B. anthracis
      reflects colonial-era importation of specific genotypes from the Old World into
      the New World, as well as the repeated industrial importation of diverse
      genotypes into developed countries via spore-contaminated animal products. These
      findings indicate humans have played an important role in the evolution of
      anthrax by increasing the proliferation and dispersal of this now global disease.
      Finally, the value of global genotypic analysis for investigating bioterrorist
      mediated outbreaks of anthrax is demonstrated.

PMID- 17520021
TI  - Positive selection within the Schizophrenia-associated GABA(A) receptor beta(2)
      gene.
AB  - The gamma-aminobutyric acid type-A (GABA(A)) receptor plays a major role in
      inhibitory neurotransmissions. Intronic SNPs and haplotypes in GABRB2, the gene
      for GABA(A) receptor beta(2) subunit, are associated with schizophrenia and
      correlated with the expression of two alternatively spliced beta(2) isoforms. In
      the present study, using chimpanzee as an ancestral reference, high frequencies
      were observed for the derived (D) alleles of the four SNPs rs6556547, rs187269,
      rs1816071 and rs1816072 in GABRB2, suggesting the occurrence of positive
      selection for these derived alleles. Coalescence-based simulation showed that the
      population frequency spectra and the frequencies of H56, the haplotype having all
      four D alleles, significantly deviated from neutral-evolution expectation in
      various demographic models. Haplotypes containing the derived allele of rs1816072
      displayed significantly less diversity compared to haplotypes containing its
      ancestral allele, further supporting positive selection. The variations in DD
      genotype frequencies in five human populations provided a snapshot of the
      evolutionary history, which suggested that the positive selections of the D
      alleles are recent and likely ongoing. The divergence between the DD-genotype
      profiles of schizophrenic and control samples pointed to the schizophrenia
      relevance of positive selections, with the schizophrenic samples showing weakened
      selections compared to the controls. These DD-genotypes were previously found to
      increase the expression of beta(2), especially its long isoform.
      Electrophysiological analysis showed that this long beta(2) isoform favored by
      the positive selections is more sensitive than the short isoform to the
      inhibition of GABA(A) receptor function by energy depletion. These findings
      represent the first demonstration of positive selection in a schizophrenia
      associated gene.

PMID- 17520022
TI  - A novel motif identified in dependence receptors.
AB  - Programmed cell death signaling is a critical feature of development, cellular
      turnover, oncogenesis, and neurodegeneration, among other processes. Such
      signaling may be transduced via specific receptors, either following ligand
      binding-to death receptors-or following the withdrawal of trophic ligands-from
      dependence receptors. Although dependence receptors display functional
      similarities, no common structural domains have been identified. Therefore, we
      employed the Multiple Expectation Maximization for Motif Elicitation and the
      Motif Alignment and Search Tool software programs to identify a novel
      transmembrane motif, dubbed dependence-associated receptor transmembrane (DART)
      motif, that is common to all described dependence receptors. Of 3,465 human
      transmembrane proteins, 25 (0.7%) display the DART motif. The predicted secondary
      structure features an alpha helical structure, with an unusually high percentage
      of valine residues. At least four of the proteins undergo regulated intramembrane
      proteolysis. To date, we have not identified a function for this putative domain.
      We speculate that the DART motif may be involved in protein processing,
      interaction with other proteins or lipids, or homomultimerization.

PMID- 17520023
TI  - Predicting pneumonia and influenza mortality from morbidity data.
AB  - BACKGROUND: Few European countries conduct reactive surveillance of influenza
      mortality, whereas most monitor morbidity. METHODOLOGY/PRINCIPAL FINDINGS: We
      developed a simple model based on Poisson seasonal regression to predict excess
      cases of pneumonia and influenza mortality during influenza epidemics, based on
      influenza morbidity data and the dominant types/subtypes of circulating viruses.
      Epidemics were classified in three levels of mortality burden ("high", "moderate"
      and "low"). The model was fitted on 14 influenza seasons and was validated on six
      subsequent influenza seasons. Five out of the six seasons in the validation set
      were correctly classified. The average absolute difference between observed and
      predicted mortality was 2.8 per 100,000 (18% of the average excess mortality) and
      Spearman's rank correlation coefficient was 0.89 (P = 0.05).
      CONCLUSIONS/SIGNIFICANCE: The method described here can be used to estimate the
      influenza mortality burden in countries where specific pneumonia and influenza
      mortality surveillance data are not available.

PMID- 17520024
TI  - Resistance exercise reverses aging in human skeletal muscle.
AB  - Human aging is associated with skeletal muscle atrophy and functional impairment
      (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction
      is a major contributor to sarcopenia. We evaluated whether healthy aging was
      associated with a transcriptional profile reflecting mitochondrial impairment and
      whether resistance exercise could reverse this signature to that approximating a
      younger physiological age. Skeletal muscle biopsies from healthy older (N = 25)
      and younger (N = 26) adult men and women were compared using gene expression
      profiling, and a subset of these were related to measurements of muscle strength.
      14 of the older adults had muscle samples taken before and after a six-month
      resistance exercise-training program. Before exercise training, older adults were
      59% weaker than younger, but after six months of training in older adults,
      strength improved significantly (P<0.001) such that they were only 38% lower than
      young adults. As a consequence of age, we found 596 genes differentially
      expressed using a false discovery rate cut-off of 5%. Prior to the exercise
      training, the transcriptome profile showed a dramatic enrichment of genes
      associated with mitochondrial function with age. However, following exercise
      training the transcriptional signature of aging was markedly reversed back to
      that of younger levels for most genes that were affected by both age and
      exercise. We conclude that healthy older adults show evidence of mitochondrial
      impairment and muscle weakness, but that this can be partially reversed at the
      phenotypic level, and substantially reversed at the transcriptome level,
      following six months of resistance exercise training.

PMID- 17520025
TI  - Anthrax toxins induce shock in rats by depressed cardiac ventricular function.
AB  - Anthrax infections are frequently associated with severe and often irreversible
      hypotensive shock. The isolated toxic proteins of Bacillus anthracis produce a
      non-cytokine-mediated hypotension in rats by unknown mechanisms. These
      observations suggest the anthrax toxins have direct cardiovascular effects. Here,
      we characterize these effects. As a first step, we administered systemically
      anthrax lethal toxin (LeTx) and edema toxin (EdTx) to cohorts of three to twelve
      rats at different doses and determined the time of onset, degree of hypotension
      and mortality. We measured serum concentrations of the protective antigen (PA)
      toxin component at various time points after infusion. Peak serum levels of PA
      were in the microg/mL range with half-lives of 10-20 minutes. With doses that
      produced hypotension with delayed lethality, we then gave bolus intravenous
      infusions of toxins to groups of four to six instrumented rats and continuously
      monitored blood pressure by telemetry. Finally, the same doses used in the
      telemetry experiments were given to additional groups of four rats, and
      echocardiography was performed pretreatment and one, two, three and twenty-four
      hours post-treatment. LeTx and EdTx each produced hypotension. We observed a
      doubling of the velocity of propagation and 20% increases in left ventricular
      diastolic and systolic areas in LeTx-treated rats, but not in EdTx-treated rats.
      EdTx-but not LeTx-treated rats showed a significant increase in heart rate. These
      results indicate that LeTx reduced left ventricular systolic function and EdTx
      reduced preload. Uptake of toxins occurs readily into tissues with biological
      effects occurring within minutes to hours of serum toxin concentrations in the
      microg/mL range. LeTx and EdTx yield an irreversible shock with subsequent death.
      These findings should provide a basis for the rational design of drug
      interventions to reduce the dismal prognosis of systemic anthrax infections.

PMID- 17520026
TI  - Structural insights into the evolution of a non-biological protein: importance of
      surface residues in protein fold optimization.
AB  - Phylogenetic profiling of amino acid substitution patterns in proteins has led
      many to conclude that most structural information is carried by interior core
      residues that are solvent inaccessible. This conclusion is based on the
      observation that buried residues generally tolerate only conserved sequence
      changes, while surface residues allow more diverse chemical substitutions. This
      notion is now changing as it has become apparent that both core and surface
      residues play important roles in protein folding and stability. Unfortunately,
      the ability to identify specific mutations that will lead to enhanced stability
      remains a challenging problem. Here we discuss two mutations that emerged from an
      in vitro selection experiment designed to improve the folding stability of a non
      biological ATP binding protein. These mutations alter two solvent accessible
      residues, and dramatically enhance the expression, solubility, thermal stability,
      and ligand binding affinity of the protein. The significance of both mutations
      was investigated individually and together, and the X-ray crystal structures of
      the parent sequence and double mutant protein were solved to a resolution limit
      of 2.8 and 1.65 A, respectively. Comparative structural analysis of the evolved
      protein to proteins found in nature reveals that our non-biological protein
      evolved certain structural features shared by many thermophilic proteins. This
      experimental result suggests that protein fold optimization by in vitro selection
      offers a viable approach to generating stable variants of many naturally
      occurring proteins whose structures and functions are otherwise difficult to
      study.

PMID- 17520027
TI  - Conformational proofreading: the impact of conformational changes on the
      specificity of molecular recognition.
AB  - To perform recognition, molecules must locate and specifically bind their targets
      within a noisy biochemical environment with many look-alikes. Molecular
      recognition processes, especially the induced-fit mechanism, are known to involve
      conformational changes. This raises a basic question: Does molecular recognition
      gain any advantage by such conformational changes? By introducing a simple
      statistical-mechanics approach, we study the effect of conformation and
      flexibility on the quality of recognition processes. Our model relates
      specificity to the conformation of the participant molecules and thus suggests a
      possible answer: Optimal specificity is achieved when the ligand is slightly off
      target; that is, a conformational mismatch between the ligand and its main target
      improves the selectivity of the process. This indicates that deformations upon
      binding serve as a conformational proofreading mechanism, which may be selected
      for via evolution.

PMID- 17520028
TI  - Nicotine protects kidney from renal ischemia/reperfusion injury through the
      cholinergic anti-inflammatory pathway.
AB  - Kidney ischemia/reperfusion injury (I/R) is characterized by renal dysfunction
      and tubular damages resulting from an early activation of innate immunity.
      Recently, nicotine administration has been shown to be a powerful inhibitor of a
      variety of innate immune responses, including LPS-induced toxaemia. This
      cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine
      receptor (alpha7nAChR). Herein, we tested the potential protective effect of
      nicotine administration in a mouse model of renal I/R injury induced by bilateral
      clamping of kidney arteries. Renal function, tubular damages and inflammatory
      response were compared between control animals and mice receiving nicotine at the
      time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in
      a dose-dependent manner and through the alpha7nAChR, as attested by the absence
      of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly
      reduced tubular damages, prevented neutrophil infiltration and decreased
      productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high
      mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice
      was associated with a decrease in tubular cell apoptosis and proliferative
      response as attested by the reduction of caspase-3 and Ki67 positive cells,
      respectively. All together, these data highlight that nicotine exerts a
      protective anti-inflammatory effect during kidney I/R through the cholinergic
      alpha7nAChR pathway. In addition, this could provide an opportunity to overcome
      the effect of surgical cholinergic denervation during kidney transplantation.

PMID- 17520029
TI  - Statins disrupt CCR5 and RANTES expression levels in CD4(+) T lymphocytes in
      vitro and preferentially decrease infection of R5 versus X4 HIV-1.
AB  - BACKGROUND: Statins have previously been shown to reduce the in vitro infection
      of human immunodeficiency virus type 1 (HIV-1) through modulation of Rho GTPase
      activity and lipid raft formation at the cell surface, as well as by disrupting
      LFA-1 incorporation into viral particles. PRINCIPLE FINDINGS: Here we demonstrate
      that treatment of an enriched CD4(+) lymphocyte population with lovastatin (Lov),
      mevastatin (Mev) and simvastatin (activated and non-activated, Sim(A) and Sim(N),
      respectively) can reduce the cell surface expression of the CC-chemokine receptor
      CCR5 (P<0.01 for Sim(A) and Lov). The lowered CCR5 expression was associated with
      down-regulation of CCR5 mRNA expression. The CC-chemokine RANTES protein and mRNA
      expression levels were slightly increased in CD4(+) enriched lymphocytes treated
      with statins. Both R5 and X4 HIV-1 were reduced for their infection of statin
      treated cells; however, in cultures where statins were removed and where a
      decrease in CCR5 expression was observed, there was a preferential inhibition of
      infection with an R5 versus X4 virus. CONCLUSIONS: The results indicate that the
      modulation of CC-chemokine receptor (CCR5) and CC-chemokine (RANTES) expression
      levels should be considered as contributing to the anti-viral effects of statins,
      preferentially inhibiting R5 viruses. This observation, in combination with the
      immunomodulatory activity exerted by statins, suggests they may possess more
      potent anti-HIV-1 activity when applied during the early stages of infection or
      in lowering viral transmission. Alternatively, statin treatment could be
      considered as a way to modulate immune induction such as during vaccination
      protocols.

PMID- 17520030
TI  - The Chernobyl nuclear catastrophe: unacknowledged health detriment.

PMID- 17520032
TI  - Chlorinated pools and the risk of asthma.

PMID- 17520034
TI  - Exploring developmental origins of obesity.

PMID- 17520036
TI  - Where space and ocean meet.

PMID- 17520040
TI  - Society builds sustainability in Africa.

PMID- 17520043
TI  - Of mice and women.

PMID- 17520044
TI  - Perfluoroalkyl acids: what is the evidence telling us?

PMID- 17520045
TI  - Radical departure: polymerization does more with less.

PMID- 17520046
TI  - Short-term particulate threat. Pollution standard may not protect health.

PMID- 17520047
TI  - Arsenic upsets heartbeat. Possible early warning for cardiovascular risk.

PMID- 17520048
TI  - Cottonwood clues in Fallon. Tree rings reflect tungsten, cobalt exposure.

PMID- 17520049
TI  - Toxic neighbors? Fetal death risk near hazardous waste sites.

PMID- 17520050
TI  - What do we feed to food-production animals? A review of animal feed ingredients
      and their potential impacts on human health.
AB  - OBJECTIVE: Animal feeding practices in the United States have changed
      considerably over the past century. As large-scale, concentrated production
      methods have become the predominant model for animal husbandry, animal feeds have
      been modified to include ingredients ranging from rendered animals and animal
      waste to antibiotics and organoarsenicals. In this article we review current U.S.
      animal feeding practices and etiologic agents that have been detected in animal
      feed. Evidence that current feeding practices may lead to adverse human health
      impacts is also evaluated. DATA SOURCES: We reviewed published veterinary and
      human-health literature regarding animal feeding practices, etiologic agents
      present in feed, and human health effects along with proceedings from animal feed
      workshops. DATA EXTRACTION: Data were extracted from peer-reviewed articles and
      books identified using PubMed, Agricola, U.S. Department of Agriculture, Food and
      Drug Administration, and Centers for Disease Control and Prevention databases.
      DATA SYNTHESIS: Findings emphasize that current animal feeding practices can
      result in the presence of bacteria, antibiotic-resistant bacteria, prions,
      arsenicals, and dioxins in feed and animal-based food products. Despite a range
      of potential human health impacts that could ensue, there are significant data
      gaps that prevent comprehensive assessments of human health risks associated with
      animal feed. Limited data are collected at the federal or state level concerning
      the amounts of specific ingredients used in animal feed, and there are
      insufficient surveillance systems to monitor etiologic agents "from farm to
      fork." CONCLUSIONS: Increased funding for integrated veterinary and human health
      surveillance systems and increased collaboration among feed professionals, animal
      producers, and veterinary and public health officials is necessary to effectively
      address these issues.

PMID- 17520051
TI  - The OECD program to validate the rat Hershberger bioassay to screen compounds for
      in vivo androgen and antiandrogen responses: phase 2 dose-response studies.
AB  - OBJECTIVE: The Organisation for Economic Co-operation and Development (OECD) has
      completed phase 2 of an international program to validate the rodent Hershberger
      bioassay. DESIGN: The Hershberger bioassay is designed to identify suspected
      androgens and antiandrogens based on changes in the weights of five androgen
      responsive tissues (ventral prostate, paired seminal vesicles and coagulating
      glands, the levator ani and bulbocavernosus muscles, the glans penis, and paired
      Cowper's or bulbourethral glands). Protocol sensitivity and reproducibility were
      tested using two androgen agonists (17alpha-methyl testosterone and 17beta
      trenbolone), four antagonists [procymi-done, vinclozolin, linuron, and 1,1
      dichoro-2,2-bis-(p-chlorophenyl)ethylene (p,p'-DDE)], and a 5alpha-reductase
      inhibitor (finasteride). Sixteen laboratories from seven countries participated
      in phase 2. RESULTS: In 40 of 41 studies, the laboratories successfully detected
      substance-related weight changes in one or more tissues. The one exception was
      with the weakest antiandrogen, linuron, in a laboratory with reduced sensitivity
      because of high coefficients of variation in all tissue weights. The protocols
      performed well under different experimental conditions (e.g., strain, diet,
      housing protocol, bedding, vehicle). There was good agreement and reproducibility
      among laboratories with regard to the lowest dose inducing significant effects on
      tissue weights. CONCLUSIONS: The results show that the OECD Hershberger bioassay
      protocol is reproducible and transferable across laboratories with androgen
      agonists, weak androgen antagonists, and a 5alpha-reductase inhibitor. The next
      validation phase will employ coded test substances, including positive substances
      and negative substances having no androgenic or antiandrogenic activity.

PMID- 17520052
TI  - Mortality effects of a copper smelter strike and reduced ambient sulfate
      particulate matter air pollution.
AB  - BACKGROUND: Numerous studies have reported associations between fine particulate
      and sulfur oxide air pollution and human mortality. Yet there continues to be
      concern that public policy efforts to improve air quality may not produce actual
      improvement in human health. OBJECTIVES: This study retrospectively explored a
      natural experiment associated with a copper smelter strike from 15 July 1967
      through the beginning of April 1968. METHODS: In the 1960s, copper smelters
      accounted for approximately 90% of all sulfate emissions in the four Southwest
      states of New Mexico, Arizona, Utah, and Nevada. Over the 8.5-month strike
      period, a regional improvement in visibility accompanied an approximately 60%
      decrease in concentrations of suspended sulfate particles. We collected monthly
      mortality counts for 1960-1975 and analyzed them using Poisson regression models.
      RESULTS: The strike-related estimated percent decrease in mortality was 2.5% (95%
      confidence interval, 1.1-4.0%), based on a Poisson regression model that
      controlled for time trends, mortality counts in bordering states, and nationwide
      mortality counts for influenza/pneumonia, cardiovascular, and other respiratory
      deaths. CONCLUSIONS: These results contribute to the growing body of evidence
      that ambient sulfate particulate matter and related air pollutants are adversely
      associated with human health and that the reduction in this pollution can result
      in reduced mortality.

PMID- 17520053
TI  - Linkage of the California Pesticide Use Reporting Database with spatial land use
      data for exposure assessment.
AB  - BACKGROUND: The State of California maintains a comprehensive Pesticide Use
      Reporting Database (CPUR). The California Department of Water Resources (CDWR)
      maps all crops in agricultural counties in California about once every 5 years.
      OBJECTIVE: We integrated crop maps with CPUR to more accurately locate where
      pesticides are applied and evaluated the effects for exposure assessment.
      METHODS: We mapped 577 residences and used the CPUR and CDWR data to compute two
      exposure metrics based on putative pesticide use within a 500-m buffer. For the
      CPUR metric, we assigned pesticide exposure to the residence proportionally for
      all square-mile Sections that intersected the buffer. For the CDWR metric, we
      linked CPUR crop-specific pesticide use to crops mapped within the buffer and
      assigned pesticide exposure. We compared the metrics for six pesticides:
      simazine, trifluralin (herbicides), dicofol, propargite (insecticides), methyl
      bromide, and metam sodium (fumigants). RESULTS: For all six pesticides we found
      good agreement (88-98%) as to whether the pesticide use was predicted. When we
      restricted the analysis to residences with reported pesticide use in Sections
      within 500 m, agreement was greatly reduced (35-58%). The CPUR metric estimates
      of pesticide use within 500 m were significantly higher than the CDWR metric for
      all six pesticides. CONCLUSIONS: Our findings may have important implications for
      exposure classification in epidemiologic studies of agricultural pesticide use
      using CPUR. There is a need to conduct environmental and biological measurements
      to ascertain which, if any, of these metrics best represent exposure.

PMID- 17520054
TI  - Chronic arsenic exposure and cardiac repolarization abnormalities with QT
      interval prolongation in a population-based study.
AB  - BACKGROUND: Chronic arsenic exposure is associated with cardiovascular
      abnormalities. Prolongation of the QT (time between initial deflection of QRS
      complex to the end of T wave) interval and profound repolarization changes on
      electrocardiogram (ECG) have been reported in patients with acute promyelocytic
      leukemia treated with arsenic trioxide. This acquired form of long QT syndrome
      can result in life-threatening arrhythmias. OBJECTIVE: The objective of this
      study was to assess the cardiac effects of arsenic by investigating QT interval
      alterations in a human population chronically exposed to arsenic. METHODS:
      Residents in Ba Men, Inner Mongolia, have been chronically exposed to arsenic via
      consumption of water from artesian wells. A total of 313 Ba Men residents with
      the mean arsenic exposure of 15 years were divided into three arsenic exposure
      groups: low (< or = 21 microg/L), medium (100-300 microg/L), and high (430-690
      microg/L). ECGs were obtained on all study subjects. The normal range for QTc
      (corrected QT) interval is 0.33-0.44 sec, and QTc > or = 0.45 sec was considered
      to be prolonged. RESULTS: The prevalence rates of QT prolongation and water
      arsenic concentrations showed a dose-dependent relationship (p = 0.001). The
      prevalence rates of QTc prolongation were 3.9, 11.1, 20.6% for low, medium, and
      high arsenic exposure, respectively. QTc prolongation was also associated with
      sex (p < 0.0001) but not age (p = 0.486) or smoking (p = 0.1018). Females were
      more susceptible to QT prolongation than males. CONCLUSIONS: We found significant
      association between chronic arsenic exposure and QT interval prolongation in a
      human population. QT interval may potentially be useful in the detection of early
      cardiac arsenic toxicity.

PMID- 17520055
TI  - Elevated lead in drinking water in Washington, DC, 2003-2004: the public health
      response.
AB  - BACKGROUND: In 2003, residents of the District of Columbia (DC) experienced an
      abrupt rise in lead levels in drinking water, which followed a change in water
      disinfection treatment in 2001 and which was attributed to consequent changes in
      water chemistry and corrosivity. OBJECTIVES: To evaluate the public health
      implications of the exceedance, the DC Department of Health expanded the scope of
      its monitoring programs for blood lead levels in children. METHODS: From 3
      February 2004 to 31 July 2004, 6,834 DC residents were screened to determine
      their blood lead levels. RESULTS: Children from 6 months to 6 years of age
      constituted 2,342 of those tested; 65 had blood lead levels > 10 microg/dL (the
      "level of concern" defined by the Centers for Disease Control and Prevention),
      the highest with a level of 68 microg/dL. Investigation of their homes identified
      environmental sources of lead exposure other than tap water as the source, when
      the source was identified. Most of the children with elevated blood lead levels
      (n = 46; 70.8%) lived in homes without lead drinking-water service lines, which
      is the principal source of lead in drinking water in older cities. Although
      residents of houses with lead service lines had higher blood lead levels on
      average than those in houses that did not, this relationship is confounded. Older
      houses that retain lead service lines usually have not been rehabilitated and are
      more likely to be associated with other sources of exposure, particularly lead
      paint. None of 96 pregnant women tested showed blood lead levels > 10 microg/dL,
      but two nursing mothers had blood lead levels > 10 microg/dL. Among two data sets
      of 107 and 71 children for whom paired blood and water lead levels could be
      obtained, there was no correlation (r(2) = -0.03142 for the 107). CONCLUSIONS:
      The expanded screening program developed in response to increased lead levels in
      water uncovered the true dimensions of a continuing problem with sources of lead
      in homes, specifically lead paint. This study cannot be used to correlate lead in
      drinking water with blood lead levels directly because it is based on an ecologic
      rather than individualized exposure assessment; the protocol for measuring lead
      was based on regulatory requirements rather than estimating individual intake;
      numerous interventions were introduced to mitigate the effect; exposure from
      drinking water is confounded with other sources of lead in older houses; and the
      period of potential exposure was limited and variable.

PMID- 17520056
TI  - Tetrahydrofurandiols (THF-diols), leukotoxindiols (LTX-diols), and endocrine
      disruption in rats.
AB  - BACKGROUND: Ground corncob animal bedding and corn food products contain
      substances that disrupt endocrine function in rats. The disruptors were
      identified as isomeric mixtures of tetrahydrofurandiols (THF-diols; 9,12-oxy
      10,13-dihydroxyoctadecanoic acid and 10,13-oxy-9,12-dihydroxyoctadecanoic acid)
      and leukotoxindiols (LTX-diols; 9,10-dihydroxy-12-octadecenoic acid and 12,13
      dihydroxy-9-octadecenoic acid). The authentic compounds blocked sexual behavior
      in male rats and estrous cyclicity in female rats at oral doses of 2 ppm.
      OBJECTIVES: To define the lowest observed adverse effect level (LOAEL) for the
      THF-diols and LTX-diols in rats, we examined the nature of their interaction
      (additive or synergistic) and quantified the concentration of THF-diols in rat
      tissues. METHODS: Adult male and female rats were provided drinking solutions
      containing various doses of THF-diols and/or LTX-diols, and we evaluated their
      effects on male sexual behavior and female estrous cyclicity. Tissues were
      collected for THF-diol determination by gas chromatography-mass spectrometry.
      RESULTS: The LOAEL for THF-diols and LTX-diols for blocking estrous cyclicity was
      0.5-1.0 ppm and 0.2-0.5 ppm, respectively. Higher concentrations (1-2 ppm) of THF
      diols were required to block male sexual behavior. Combination studies with
      subthreshold doses of 0.05 ppm THF-diols plus 0.05 ppm LTX-diols revealed that
      their effects on estrous cyclicity were not synergistic. We were unable to detect
      THF-diols in tissues from rats treated with 10 ppm of the compounds, suggesting
      that metabolism may be involved. DISCUSSION: THF-diols, LTX-diols, and/or their
      metabolites likely act additively to disrupt endocrine function in male and
      female rats at concentrations (0.5-1 ppm) that are 200-fold lower than those of
      classical phytoestrogen endocrine disruptors.

PMID- 17520057
TI  - Coarse particulate matter (PM2.5-10) affects heart rate variability, blood
      lipids, and circulating eosinophils in adults with asthma.
AB  - INTRODUCTION: We investigated whether markers of airway and systemic
      inflammation, as well as heart rate variability (HRV) in asthmatics, change in
      response to fluctuations in ambient particulate matter (PM) in the coarse [PM
      with aerodynamic diameter 2.5-10 microm (PM(2.5-10))] and fine (PM(2.5)) size
      range. METHODS: Twelve adult asthmatics, living within a 30-mile radius of an
      atmospheric monitoring site in Chapel Hill, North Carolina, were followed over a
      12-week period. Daily PM(2.5-10) and PM(2.5) concentrations were measured
      separately for each 24-hr period. Each subject had nine clinic visits, at which
      spirometric measures and peripheral blood samples for analysis of lipids,
      inflammatory cells, and coagulation-associated proteins were obtained. We also
      assessed HRV [SDNN24HR (standard deviation of all normal-to-normal intervals in a
      24-hr recording), ASDNN5 (mean of the standard deviation in all 5-min segments of
      a 24-hr recording)] with four consecutive 24-hr ambulatory electrocardiogram
      measurements. Linear mixed models with a spatial covariance matrix structure and
      a 1-day lag were used to assess potential associations between PM levels and
      cardiopulmonary end points. RESULTS: For a 1-microg/m(3) increase in coarse PM,
      SDNN24HR, and ASDNN5 decreased 3.36% (p = 0.02), and 0.77%, (p = 0.05)
      respectively. With a 1-microg/m(3) increase in coarse PM, circulating eosinophils
      increased 0.16% (p = 0.01), triglycerides increased 4.8% (p = 0.02), and very low
      density lipoprotein increased 1.15% (p = 0.01). No significant associations were
      found with fine PM, and none with lung function. CONCLUSION: These data suggest
      that small temporal increases in ambient coarse PM are sufficient to affect
      important cardiopulmonary and lipid parameters in adults with asthma. Coarse PM
      may have underappreciated health effects in susceptible populations.

PMID- 17520058
TI  - Temporal variability of tungsten and cobalt in Fallon, Nevada.
AB  - BACKGROUND: Since 1997, Fallon, Nevada, has experienced a cluster of childhood
      leukemia that has been declared "one of the most unique clusters of childhood
      cancer ever reported." Multiple environmental studies have shown airborne
      tungsten and cobalt to be elevated within Fallon, but the question remains: Have
      these metals changed through time in correspondence with the onset of the
      leukemia cluster? METHODS: We used dendrochemistry, the study of element
      concentrations through time in tree rings, in Fallon to assess temporal
      variability of airborne tungsten and cobalt since the late 1980s. The techniques
      used in Fallon were also tested in a different town (Sweet Home, OR) that has
      airborne tungsten from a known source. RESULTS: The Sweet Home test case confirms
      the accuracy of dendrochemistry for showing temporal variability of environmental
      tungsten. Given that dendrochemistry works for tungsten, tree-ring chemistry
      shows that tungsten increased in Fallon relative to nearby comparison towns
      beginning by the mid-1990s, slightly before the onset of the cluster, and cobalt
      has been high throughout the last approximately 15 years. Other metals do not
      show trends through time in Fallon. DISCUSSION: Results in Fallon suggest a
      temporal correspondence between the onset of excessive childhood leukemia and
      elevated levels of tungsten and cobalt. Although environmental data alone cannot
      directly link childhood leukemia with exposure to metals, research by others has
      shown that combined exposure to tungsten and cobalt can be carcinogenic to
      humans. CONCLUSION: Continued biomedical research is warranted to directly test
      for linkage between childhood leukemia and tungsten and cobalt.

PMID- 17520059
TI  - Atrazine-induced aromatase expression is SF-1 dependent: implications for
      endocrine disruption in wildlife and reproductive cancers in humans.
AB  - BACKGROUND: Atrazine is a potent endocrine disruptor that increases aromatase
      expression in some human cancer cell lines. The mechanism involves the inhibition
      of phosphodiesterase and subsequent elevation of cAMP. METHODS: We compared
      steroidogenic factor 1 (SF-1) expression in atrazine responsive and non
      responsive cell lines and transfected SF-1 into nonresponsive cell lines to
      assess SF-1's role in atrazine-induced aromatase. We used a luciferase reporter
      driven by the SF-1-dependent aromatase promoter (ArPII) to examine activation of
      this promoter by atrazine and the related simazine. We mutated the SF-1 binding
      site to confirm the role of SF-1. We also examined effects of 55 other chemicals.
      Finally, we examined the ability of atrazine and simazine to bind to SF-1 and
      enhance SF-1 binding to ArPII. RESULTS: Atrazine-responsive adrenal carcinoma
      cells (H295R) expressed 54 times more SF-1 than nonresponsive ovarian granulosa
      KGN cells. Exogenous SF-1 conveyed atrazine-responsiveness to otherwise
      nonresponsive KGN and NIH/3T3 cells. Atrazine induced binding of SF-1 to
      chromatin and mutation of the SF-1 binding site in ArPII eliminated SF-1 binding
      and atrazine-responsiveness in H295R cells. Out of 55 chemicals examined, only
      atrazine, simazine, and benzopyrene induced luciferase via ArPII. Atrazine bound
      directly to SF-1, showing that atrazine is a ligand for this "orphan" receptor.
      CONCLUSION: The current findings are consistent with atrazine's endocrine
      disrupting effects in fish, amphibians, and reptiles; the induction of mammary
      and prostate cancer in laboratory rodents; and correlations between atrazine and
      similar reproductive cancers in humans. This study highlights the importance of
      atrazine as a risk factor in endocrine disruption in wildlife and reproductive
      cancers in laboratory rodents and humans.

PMID- 17520060
TI  - Efficient elimination of inhaled nanoparticles from the alveolar region: evidence
      for interstitial uptake and subsequent reentrainment onto airways epithelium.
AB  - BACKGROUND: There is ongoing discussion that inhaled nanoparticles (NPs, < 100
      nm) may translocate from epithelial deposition sites of the lungs to systemic
      circulation. OBJECTIVES AND METHODS: We studied the disappearance of NPs from the
      epithelium by sequential lung retention and clearance and bronchoalveolar lavage
      (BAL) measurements in healthy adult Wistar Kyoto (WKY) rats at various times over
      6 months after administration of a single 60- to 100-min intratracheal inhalation
      of iridium-192 ((192)Ir)-radiolabeled NPs. A complete (192)Ir balance of all
      organs, tissues, excretion, remaining carcass, and BAL was performed at each time
      point. RESULTS: Directly after inhalation we found free NPs in the BAL; later,
      NPs were predominantly associated with alveolar macropages (AMs). After 3 weeks,
      lavageable NP fractions decreased to 0.06 of the actual NP lung burden. This is
      in stark contrast to the AM-associated fraction of micron-sized particles
      reported in the literature. These particles remained constant at about 0.8
      throughout a 6-month period. Three weeks after inhalation, 80% of the retained Ir
      NPs was translocated into epithelium and interstitium. CONCLUSION: There is a
      strong size-selective difference in particle immobilization. Furthermore, AM
      mediated NP transport to the larynx originates not only from the NP fraction
      retained on the epithelium but also from NPs being reentrained from the
      interstitium to the luminal side of epithelium. We conclude that NPs are much
      less phagocytized by AMs than large particles but are effectively removed from
      the lung surface into the interstitium. Even from these interstitial sites, they
      undergo AM-mediated long-term NP clearance to the larynx.

PMID- 17520061
TI  - Molecular mechanisms of the diabetogenic effects of arsenic: inhibition of
      insulin signaling by arsenite and methylarsonous acid.
AB  - BACKGROUND: Increased prevalences of diabetes mellitus have been reported among
      individuals chronically exposed to inorganic arsenic (iAs). However, the
      mechanisms underlying the diabetogenic effects of iAs have not been
      characterized. We have previously shown that trivalent metabolites of iAs,
      arsenite (iAs(III)) and methylarsonous acid (MAs(III)) inhibit insulin-stimulated
      glucose uptake (ISGU) in 3T3-L1 adipocytes by suppressing the insulin-dependent
      phosphorylation of protein kinase B (PKB/Akt). OBJECTIVES: Our goal was to
      identify the molecular mechanisms responsible for the suppression of PKB/Akt
      phosphorylation by iAs(III) and MAs(III). METHODS: The effects of iAs(III) and
      MAs(III) on components of the insulin-activated signal transduction pathway that
      regulate PKB/Akt phosphorylation were examined in 3T3-L1 adipocytes. RESULTS:
      Subtoxic concentrations of iAs(III) or MAs(III) had little or no effect on the
      activity of phosphatidylinositol 3-kinase (PI-3K), which synthesizes
      phosphatidylinositol-3,4,5-triphosphate (PIP(3)), or on phosphorylation of PTEN
      (phosphatase and tensin homolog deleted on chromosome ten), a PIP(3) phosphatase.
      Neither iAs(III) nor MAs(III) interfered with the phosphorylation of 3
      phosphoinositide-dependent kinase-1 (PDK-1) located downstream from PI-3K.
      However, PDK-1 activity was inhibited by both iAs(III) and MAs(III). Consistent
      with these findings, PDK-1-catalyzed phosphorylation of PKB/Akt(Thr308) and
      PKB/Akt activity were suppressed in exposed cells. In addition, PKB/Akt(Ser473)
      phosphorylation, which is catalyzed by a putative PDK-2, was also suppressed.
      Notably, expression of constitutively active PKB/Akt restored the normal ISGU
      pattern in adipocytes treated with either iAs(III) or MAs(III). CONCLUSIONS:
      These results suggest that inhibition of the PDK-1/PKB/Akt-mediated transduction
      step is the key mechanism for the inhibition of ISGU in adipocytes exposed to
      iAs(III) or MAs(III), and possibly for impaired glucose tolerance associated with
      human exposures to iAs.

PMID- 17520062
TI  - Quantifying the efficiency and equity implications of power plant air pollution
      control strategies in the United States.
AB  - BACKGROUND: In deciding among competing approaches for emissions control, debates
      often hinge on the potential tradeoffs between efficiency and equity. However,
      previous health benefits analyses have not formally addressed both dimensions.
      OBJECTIVES: We modeled the public health benefits and the change in the spatial
      inequality of health risk for a number of hypothetical control scenarios for
      power plants in the United States to determine optimal control strategies.
      METHODS: We simulated various ways by which emission reductions of sulfur dioxide
      (SO(2)), nitrogen oxides, and fine particulate matter (particulate matter < 2.5
      microm in diameter; PM(2.5)) could be distributed to reach national emissions
      caps. We applied a source-receptor matrix to determine the PM(2.5) concentration
      changes associated with each control scenario and estimated the mortality
      reductions. We estimated changes in the spatial inequality of health risk using
      the Atkinson index and other indicators, following previously derived axioms for
      measuring health risk inequality. RESULTS: In our baseline model, benefits ranged
      from 17,000-21,000 fewer premature deaths per year across control scenarios.
      Scenarios with greater health benefits also tended to have greater reductions in
      the spatial inequality of health risk, as many sources with high health benefits
      per unit emissions of SO(2) were in areas with high background PM(2.5)
      concentrations. Sensitivity analyses indicated that conclusions were generally
      robust to the choice of indicator and other model specifications. CONCLUSIONS:
      Our analysis demonstrates an approach for formally quantifying both the magnitude
      and spatial distribution of health benefits of pollution control strategies,
      allowing for joint consideration of efficiency and equity.

PMID- 17520063
TI  - Mortality risk associated with short-term exposure to traffic particles and
      sulfates.
AB  - BACKGROUND: Many studies have shown that airborne particles are associated with
      increased risk of death, but attention has more recently focused on the
      differential toxicity of particles from different sources. Geographic information
      system (GIS) approaches have recently been used to improve exposure assessment,
      particularly for traffic particles, but only for long-term exposure. OBJECTIVES:
      We analyzed approximately 100,000 deaths from all, cardiovascular, and
      respiratory causes for the years 1995-2002 using a case-crossover analysis.
      METHODS: Estimates of exposure to traffic particles were geocoded to the address
      of each decedent on the day before death and control days, with these estimates
      derived from a GIS-based exposure model incorporating deterministic covariates,
      such as traffic density and meteorologic factors, and a smooth function of
      latitude and longitude. RESULTS: We estimate that an IQR increase in traffic
      particle exposure on the day before death is associated with a 2.3% increase [95%
      confidence interval (CI), 1.2 to 3.4%] in all-cause mortality risk. Stroke deaths
      were particularly elevated (4.4%; 95% CI, -0.2 to 9.3%), as were diabetes deaths
      (5.7%; 95% CI, -1.7 to 13.7%). Sulfate particles are spatially homogeneous, and
      using a central monitor, we found that an IQR increase in sulfate levels on the
      day before death is associated with a 1.1% (95% CI, 0.1 to 2.0%) increase in all
      cause mortality risk. CONCLUSIONS: Both traffic and powerplant particles are
      associated with increased deaths in Boston, with larger effects for traffic
      particles.

PMID- 17520064
TI  - Proteomic analysis of bronchoalveolar lavage fluid: effect of acute exposure to
      diesel exhaust particles in rats.
AB  - BACKGROUND: Inhalation of diesel exhaust particles (DEPs) is characterized by
      lung injury and inflammation, with significant increases in the numbers of
      polymorphonuclear leukocytes and alveolar macrophages. This influx of cellular
      infiltrates is associated with the activation of multiple genes, including
      cytokines and chemokines, and the production of reactive oxygen species.
      OBJECTIVE: The pathogenesis of the lung injury is not fully understood, but
      alterations in the presence or abundance of a number of proteins in the lung have
      been observed. Our objective in this study was to further characterize these
      changes and to ask whether additional changes could be discerned using modern
      proteomic techniques. METHODS: The present study investigates global alterations
      in the proteome of bronchoalveolar lavage fluid taken from rats 1, 7, or 30 days
      after exposure to 5, 35, or 50 mg/kg of animal weight of DEPs. RESULTS: Analysis
      by surface-enhanced laser desorption/ionization-time of flight mass spectrometry
      identified two distinct peaks that appeared as an acute response postexposure at
      all doses in all animals. We identified these two peaks, with mass to charge
      ratios (m/z) of 9,100 and 10,100, as anaphylatoxin C3a and calgranulin A by
      additional mass spectral investigation using liquid chromatography coupled to
      mass spectrometry. CONCLUSIONS: With this approach, we found a number of
      inflammatory response proteins that may be associated with the early phases of
      inflammation in response to DEP exposure. Further studies are warranted to
      determine whether serum levels of these proteins could be markers of diesel
      exhaust exposure in workers.

PMID- 17520065
TI  - Meeting report: alternatives for developmental neurotoxicity testing.
AB  - Developmental neurotoxicity testing (DNT) is perceived by many stakeholders to be
      an area in critical need of alternatives to current animal testing protocols and
      guidelines. To address this need, the Johns Hopkins Center for Alternatives to
      Animal Testing (CAAT), the U.S. Environmental Protection Agency, and the National
      Toxicology Program are collaborating in a program called TestSmart DNT, the goals
      of which are to: (a) develop alternative methodologies for identifying and
      prioritizing chemicals and exposures that may cause developmental neurotoxicity
      in humans; (b) develop the policies for incorporating DNT alternatives into
      regulatory decision making; and (c) identify opportunities for reducing,
      refining, or replacing the use of animals in DNT. The first TestSmart DNT
      workshop was an open registration meeting held 13-15 March 2006 in Reston,
      Virginia. The primary objective was to bring together stakeholders (test
      developers, test users, regulators, and advocates for children's health, animal
      welfare, and environmental health) and individuals representing diverse
      disciplines (developmental neurobiology, toxicology, policy, and regulatory
      science) from around the world to share information and concerns relating to the
      science and policy of DNT. Individual presentations are available at the CAAT
      TestSmart website. This report provides a synthesis of workgroup discussions and
      recommendations for future directions and priorities, which include initiating a
      systematic evaluation of alternative models and technologies, developing a
      framework for the creation of an open database to catalog DNT data, and devising
      a strategy for harmonizing the validation process across international
      jurisdictional borders.

PMID- 17520066
TI  - Particulate air pollution, progression, and survival after myocardial infarction.
AB  - OBJECTIVE: Several studies have examined the effect of particulate pollution (PM)
      on survival in general populations, but less is known about susceptible groups.
      Moreover, previous cohort studies have been cross-sectional and subject to
      confounding by uncontrolled differences between cities. DESIGN: We investigated
      whether PM was associated with progression of disease or reduced survival in a
      study of 196,000 persons from 21 U.S. cities discharged alive following an acute
      myocardial infarction (MI), using within-city between-year exposure to PM. We
      constructed city-specific cohorts of survivors of acute MI using Medicare data
      between 1985 and 1999, and defined three outcomes on follow-up: death, subsequent
      MI, and a first admission for congestive heart failure (CHF). Yearly averages of
      PM(10) (particulate matter with aerodynamic diameter < 10 microm) were merged to
      the individual annual follow-up in each city. We applied Cox's proportional
      hazard regression model in each city, with adjustment for individual risk
      factors. In the second stage of the analysis, the city-specific results were
      combined using a meta-regression. RESULTS: We found significant associations with
      a hazard ratio for the sum of the distributed lags of 1.3 [95% confidence
      interval (CI), 1.2-1.5] for mortality, a hazard ratio of 1.4 (95% CI, 1.2-1.7)
      for a hospitalization for CHF, and a hazard ratio of 1.4 (95% CI, 1.1-1.8) for a
      new hospitalization for MI per 10 microg/m(3) PM(10). CONCLUSIONS: This is the
      first long-term study showing a significant association between particle exposure
      and adverse post-MI outcomes in persons who survived an MI.

PMID- 17520067
TI  - Fetal deaths and proximity to hazardous waste sites in Washington State.
AB  - BACKGROUND: The in utero period is one of increased susceptibility to
      environmental effects. The effects of prenatal exposure to environmental
      toxicants on various adverse pregnancy outcomes, including fetal death, are not
      well understood. OBJECTIVE: We examined the risk of fetal death in relation to
      maternal residential proximity to hazardous waste sites. METHODS: We conducted a
      population-based case-control study using Washington State vital records for 1987
      2001. Cases were women with fetal deaths at > or = 20 weeks (n = 7,054). Ten
      controls per case were randomly selected from live births. Locations of 939
      hazardous waste sites were identified from the Department of Ecology registry. We
      measured distance from maternal residence at delivery to the nearest hazardous
      waste site, and calculated odds ratios (ORs) and 95% confidence intervals (CIs).
      RESULTS: The risk of fetal death for women residing < or = 0.5 miles, relative to
      > 5 miles, from a hazardous waste site was not increased (adjusted OR = 1.06; 95%
      CI, 0.90-1.25). No associations were observed for any proximity categories < or =
      5 miles from sites with contaminated air, soil, water, solvents, or metals;
      however, fetal death risk increased among women residing < or = 1 mile from
      pesticide-containing sites (OR = 1.28; 95% CI, 1.13-1.46). CONCLUSION: These
      results do not suggest that fetal death is associated with residential proximity
      to hazardous waste sites overall; however, close proximity to pesticide
      containing sites may increase the risk of fetal death.

PMID- 17520068
TI  - The SHEDS-Wood model: incorporation of observational data to estimate exposure to
      arsenic for children playing on CCA-treated wood structures.
AB  - BACKGROUND: Lumber treated with chromated copper arsenate (CCA) compounds has
      been used in residential outdoor wood structures and public playgrounds. The U.S.
      Environmental Protection Agency (EPA) has conducted a probabilistic assessment of
      children's exposure to arsenic using the Stochastic Human Exposure and Dose
      Simulation model for the wood preservative scenario (SHEDS-Wood). The assessment
      relied on data derived from an experimental study conducted using adult
      volunteers and designed to result in maximum hand and wipe loadings to estimate
      the residue-skin transfer efficiency. Recent analyses of arsenic hand-loading
      data generated by studies of children actively involved in playing on CCA-treated
      structures indicate that the transfer efficiency coefficient and hand-loading
      estimates derived from the experimental study significantly overestimate the
      amount that occurs during actual play. OBJECTIVES: Our goal was to assess the
      feasibility of using child hand-loading data in the SHEDS-Wood model and their
      impact on exposure estimates. METHODS: We used data generated by the larger of
      the studies of children in SHEDS-Wood, instead of the distributions used by U.S.
      EPA. We compared our estimates of the lifetime average daily dose (LADD) and
      average daily dose (ADD) with those derived by the U.S. EPA. RESULTS: Our
      analysis indicates that data from observational studies of children can be used
      in SHEDS-Wood. Our estimates of the mean (and 95th percentile) LADD and ADD were
      27% (10%) and 29% (15%) of the estimates derived by U.S. EPA. CONCLUSION: We
      recommend that the SHEDS-Woods model use data from studies of children actively
      playing on playsets to more accurately estimate children's actual exposures to
      CCA.

PMID- 17520069
TI  - Case report: three farmworkers who gave birth to infants with birth defects
      closely grouped in time and place-Florida and North Carolina, 2004-2005.
AB  - CONTEXT: There is little evidence linking adverse reproductive effects to
      exposure to specific pesticides during pregnancy. CASE PRESENTATION: In February
      2005, three infants with congenital anomalies were identified in Collier County,
      Florida, who were born within 8 weeks of one another and whose mothers worked for
      the same tomato grower. The mothers worked on the grower's Florida farms in 2004
      before transferring to its North Carolina farms. All three worked during the
      period of organogenesis in fields recently treated with several pesticides. The
      Florida and North Carolina farms were inspected by regulatory agencies, and in
      each state a large number of violations were identified and record fines were
      levied. DISCUSSION: Despite the suggestive evidence, a causal link could not be
      established between pesticide exposures and the birth defects in the three
      infants. Nonetheless, the prenatal pesticide exposures experienced by the mothers
      of the three infants is cause for concern. Farmworkers need greater protections
      against pesticides. These include increased efforts to publicize and comply with
      both the U.S. Environmental Protections Agency's Worker Protection Standard and
      pesticide label requirements, enhanced procedures to ensure pesticide applicator
      competency, and recommendations to growers to adopt work practices to reduce
      pesticide exposures. RELEVANCE TO PROFESSIONAL PRACTICE: The findings from this
      report reinforce the need to reduce pesticide exposures among farmworkers. In
      addition, they support the need for epidemiologic studies to examine the role of
      pesticide exposure in the etiology of congenital anomalies.

PMID- 17520070
TI  - Organophosphate pesticide exposure and neurodevelopment in young Mexican-American
      children.
AB  - BACKGROUND: Organophosphate (OP) pesticides are widely used in agriculture and
      homes. Animal studies suggest that even moderate doses are neurodevelopmental
      toxicants, but there are few studies in humans. OBJECTIVES: We investigated the
      relationship of prenatal and child OP urinary metabolite levels with children's
      neurodevelopment. METHODS: Participating children were from a longitudinal birth
      cohort of primarily Latino farm-worker families in California. We measured six
      nonspecific dialkylphosphate (DAP) metabolites in maternal and child urine as
      well as metabolites specific to malathion (MDA) and chlorpyrifos (TCPy) in
      maternal urine. We examined their association with children's performance at 6 (n
      = 396), 12 (n = 395), and 24 (n = 372) months of age on the Bayley Scales of
      Infant Development [Mental Development (MDI) and Psychomotor Development (PDI)
      Indices] and mother's report on the Child Behavior Checklist (CBCL) (n = 356).
      RESULTS: Generally, pregnancy DAP levels were negatively associated with MDI, but
      child measures were positively associated. At 24 months of age, these
      associations reached statistical significance [per 10-fold increase in prenatal
      DAPs: beta = -3.5 points; 95% confidence interval (CI), -6.6 to -0.5; child DAPs:
      beta = 2.4 points; 95% CI, 0.5 to 4.2]. Neither prenatal nor child DAPs were
      associated with PDI or CBCL attention problems, but both prenatal and postnatal
      DAPs were associated with risk of pervasive developmental disorder [per 10-fold
      increase in prenatal DAPs: odds ratio (OR) = 2.3, p = 0.05; child DAPs OR = 1.7,
      p = 0.04]. MDA and TCPy were not associated with any outcome. CONCLUSIONS: We
      report adverse associations of prenatal DAPs with mental development and
      pervasive developmental problems at 24 months of age. Results should be
      interpreted with caution given the observed positive relationship with postnatal
      DAPs.

PMID- 17520071
TI  - If cumulative risk assessment is the answer, what is the question?
AB  - Cumulative risk refers to the combined threats from exposure via all relevant
      routes to multiple stressors including biological, chemical, physical, and
      psychosocial entities. Cumulative risk assessment is a tool for organizing and
      analyzing information to examine, characterize, and possibly quantify the
      combined adverse effects on human health or ecologic resources from multiple
      environmental stressors. The U.S. Environmental Protection Agency (EPA) has
      initiated a long-term effort to develop future guidelines for cumulative risk
      assessment, including publication in 2003 of a framework that describes important
      features of the process and discusses theoretical issues, technical matters, and
      key definitions. The framework divides the process of cumulative risk assessment
      into three interrelated phases: a) planning, scoping, and problem formulation; b)
      analysis; and c) interpretation and risk characterization. It also discusses the
      additional complexities introduced by attempts to analyze cumulative risks from
      multiple stressors and describes some of the theoretical approaches that can be
      used. The development of guidelines for cumulative risk assessment is an
      essential element in the transition of the U.S. EPA risk assessment methodology
      from a narrow focus on a single stressor, end point, source, pathway, and
      exposure route to a broader, more holistic approach involving analysis of
      combined effects of cumulative exposure to multiple stressors via all relevant
      sources, pathways, and routes.

PMID- 17520072
TI  - A phased approach for assessing combined effects from multiple stressors.
AB  - We present a phased approach for evaluating the effects of physical, biological,
      chemical, and psychosocial stressors that may act in combination. Although a
      phased concept is common to many risk-based approaches, it has not been
      explicitly outlined for the assessment of combined effects of multiple stressors.
      The approach begins with the development of appropriate conceptual models and
      assessment end points. The approach then proceeds through a screening stage
      wherein stressors are evaluated with respect to their potential importance as
      contributors to risk. Stressors are considered individually or as a combination
      of independent factors with respect to one or more common assessment end points.
      As necessary, the approach then proceeds to consider interactions among
      stressors. We make a distinction between applications that begin with effects of
      concern (effects based) or with specific stressors (stressor based). We describe
      a number of tools for use within the phased approach. The methods profiled are
      ones that have been applied to yield results that can be communicated to a wide
      audience. The latter characteristic is considered especially important because
      multiple stressor problems usually involve exposures to communities or to
      ecologic regions with many stakeholders.

PMID- 17520073
TI  - Vulnerability as a function of individual and group resources in cumulative risk
      assessment.
AB  - BACKGROUND: The field of risk assessment has focused on protecting the health of
      individual people or populations of wildlife from single risks, mostly from
      chemical exposure. The U.S. Environmental Protection Agency recently began to
      address multiple risks to communities in the "Framework for Cumulative Risk
      Assessment" [EPA/630/P02/001F. Washington DC:Risk Assessment Forum, U.S.
      Environmental Protection Agency (2003)]. Simultaneously, several reports
      concluded that some individuals and groups are more vulnerable to environmental
      risks than the general population. However, vulnerability has received little
      specific attention in the risk assessment literature. OBJECTIVE: Our objective is
      to examine the issue of vulnerability in cumulative risk assessment and present a
      conceptual framework rather than a comprehensive review of the literature. In
      this article we consider similarities between ecologic and human communities and
      the factors that make communities vulnerable to environmental risks. DISCUSSION:
      The literature provides substantial evidence on single environmental factors and
      simple conditions that increase vulnerability or reduce resilience for humans and
      ecologic systems. This observation is especially true for individual people and
      populations of wildlife. Little research directly addresses the topic of
      vulnerability in cumulative risk situations, especially at the community level.
      The community level of organization has not been adequately considered as an end
      point in either human or ecologic risk assessment. Furthermore, current
      information on human risk does not completely explain the level of response in
      cumulative risk conditions. Ecologic risk situations are similarly more complex
      and unpredictable for cases of cumulative risk. CONCLUSIONS: Psychosocial
      conditions and responses are the principal missing element for humans. We propose
      a model for including psychologic and social factors as an integral component of
      cumulative risk assessment.

PMID- 17520075
TI  - Using biomarkers to inform cumulative risk assessment.
AB  - BACKGROUND: Biomarkers are considered the method of choice for determining
      exposure to environmental contaminants and relating such exposures to health
      outcomes. However, the association between many biomarkers and outcome is not
      direct because of variability in sensitivity and susceptibility in the
      individual. OBJECTIVES: We explore the relationship between environmental
      exposures and health outcomes as mitigated by differential susceptibility in
      individuals or populations and address the question "Can biomarkers enable us to
      understand and quantify better the population burden of disease and health
      effects attributable to environmental exposures?" METHODS: We use a case-study
      approach to develop the thesis that biomarkers offer a pathway to disaggregation
      of health effects into specific, if multiple, risk factors. We offer the point of
      view that a series or array of biomarkers, including biomarkers of exposure,
      biomarkers of susceptibility, and biomarkers of effect, used in concert offer the
      best means by which to effect this disaggregation. We commence our discussion by
      developing the characteristics of an ideal biomarker, then give some examples of
      commonly used biomarkers to show the strengths and weaknesses of current usage.
      We follow this by more detailed case-study assessment outlining the state-of-the
      science in specific cases. We complete our work with recommendations regarding
      the future use of biomarkers and areas for continued development. CONCLUSIONS:
      The case studies provide examples of when and how biomarkers can be used to infer
      the source and magnitude of exposure among a set of competing sources and
      pathways. The answer to this question is chemical specific and relates to how
      well the biomarker matches the characteristics of an "ideal" biomarker-in
      particular ease of collection and persistence. The use of biomarkers in
      combination provides a better opportunity to disaggregate both source and pathway
      contributions.

PMID- 17520074
TI  - Assessing cumulative health risks from exposure to environmental mixtures - three
      fundamental questions.
AB  - Differential exposure to mixtures of environmental agents, including biological,
      chemical, physical, and psychosocial stressors, can contribute to increased
      vulnerability of human populations and ecologic systems. Cumulative risk
      assessment is a tool for organizing and analyzing information to evaluate the
      probability and seriousness of harmful effects caused by either simultaneous
      and/or sequential exposure to multiple environmental stressors. In this article
      we focus on elucidating key challenges that must be addressed to determine
      whether and to what degree differential exposure to environmental mixtures
      contributes to increased vulnerability of exposed populations. In particular, the
      emphasis is on examining three fundamental and interrelated questions that must
      be addressed as part of the process to assess cumulative risk: a) Which mixtures
      are most important from a public health perspective? and b) What is the nature
      (i.e., duration, frequency, timing) and magnitude (i.e., exposure concentration
      and dose) of relevant cumulative exposures for the population of interest? c)
      What is the mechanism (e.g., toxicokinetic or toxicodynamic) and consequence
      (e.g., additive, less than additive, more than additive) of the mixture's
      interactive effects on exposed populations? The focus is primarily on human
      health effects from chemical mixtures, and the goal is to reinforce the need for
      improved assessment of cumulative exposure and better understanding of the
      biological mechanisms that determine toxicologic interactions among mixture
      constituents.

PMID- 17520076
TI  - Advances in genetics of juvenile myoclonic epilepsies.
AB  - One by one, mutation-containing mendelian genes that cause monogenic juvenile
      myoclonic epilepsies (JME) and single nucleotide polymorphisms (SNP)
      susceptibility alleles that increase risks for nonmendelian complex JME should
      fall to the power of molecular genetics. Of 15 chromosome loci, 3 mendelian genes
      (alpha1-subunit of the GABA(A) receptor [GABRA1], chloride channel 2 gene
      [CLCN2], and Myoclonin1/EFHC1) and 2 SNP-susceptibility alleles of putative JME
      genes in epistases (bromodomain-containing protein 2 [BRD2] and connexin [Cx]-36)
      have been identified, so far. Antiepileptic drugs now can be designed against the
      specific molecular defects of JME.

PMID- 17520077
TI  - More is not better: hormones for menopausal women with epilepsy?

PMID- 17520078
TI  - Nonconvulsive seizures in the pediatric intensive care unit: out of sight, out of
      mind?

PMID- 17520079
TI  - Treatment options for hypothalamic hamartomas--no laughing matter.

PMID- 17520080
TI  - Oxcarbazepine and carbamazepine: expected and unexpected differences and
      similarities.

PMID- 17520081
TI  - Do single seizures cause neuronal death in the human hippocampus?
AB  - The question of whether repeated single seizures cause neuronal death in the
      adult human brain is of great clinical importance and might have broad
      therapeutic implications. Reviewed here are recent studies on the effects of
      repeated single seizures (in the absence of status epilepticus) on hippocampal
      volume and on neuronal death markers in blood and in surgically ablated
      hippocampi.

PMID- 17520082
TI  - Mutant batten disease protein says "no" to unsaturated fats.

PMID- 17520083
TI  - No calm before the storm: reduced GABA inhibition precedes seizures in tish rats.

PMID- 17520084
TI  - How does the balance of excitation and inhibition shift during epileptogenesis?

PMID- 17520085
TI  - On demand up-regulation of therapeutic genes in the brain: fiction or reality?

PMID- 17520086
TI  - Androgen receptor and c-Myc transcription factors as putative partners in the in
      vivo cross-talk between androgen receptor-mediated and c-Met-mediated signalling
      pathways.
AB  - Cross-talk between two signal transduction pathways leads to a negative
      regulation of androgen-induced ornithine decarboxylase (ODC) gene expression in
      the mouse kidney. One pathway is triggered by testosterone via the intracellular
      androgen receptor, AR, and the other is induced by antifolate CB 3717 or folate
      via hepatocyte growth factor and its cell membrane receptor c-Met. Here we report
      the studies of the expression of AR and c-Myc transcription factors involved in
      ODC transactivation. Administration of CB 3717 or folate decreased the expression
      of AR. In contrast, testosterone did not modify AR mRNA content but augmented the
      AR protein. Furthermore, we demonstrate that administration of folate, but not
      testosterone, increases c-Myc transcript and protein level. We also document that
      activation of both examined pathways does not decrease the testosterone-induced
      AR protein level, but markedly increases c-Myc protein which is nearly 2-fold up
      regulated compared to its level evoked solely by testosterone. We suspect that
      this pronounced increase of c-Myc protein might have functional consequences
      mirrored by down-regulated expression of AR target genes, among them ODC.

PMID- 17520087
TI  - Menadione effect on l-cysteine desulfuration in U373 cells.
AB  - The non-cytotoxic concentration (20 microM) of menadione (2-methyl-1,4
      naphthoquinone), after 1 h of incubation, leads to loss of the activity of
      rhodanese by 33%, 3-mercaptopyruvate sulfurtransferase by 20%, as well as the
      level of sulfane sulfur by about 23% and glutathione by 12%, in the culture of
      U373 cells, in comparison with the control culture. Reactive oxygen species
      generated by menadione oxidize sulfhydryl groups in active centers of the
      investigated enzymes, inhibiting them and saving cysteine for glutathione
      synthesis. A decreased sulfane sulfur level can be correlated with an oxidative
      stress.

PMID- 17520088
TI  - Responsiveness of Lycopersicon pimpinellifolium to acute UV-C exposure: histo
      cytochemistry of the injury and DNA damage.
AB  - The in vivo and in vitro effects of UV-C (254 nm) exposure (0.039 watt . m(-2) .
      s for 2 h) of currant tomato (Lycopersicon pimpinellifolium), indigenous to Peru
      and Ecuador, were assayed. H(2)O(2) deposits, dead cells and DNA damage were
      localized, 12/24 h after irradiation, mainly in periveinal parenchyma of the 1st
      and 2nd order veins of the leaves, and before the appearance of visible symptoms,
      which occurred 48 h after irradiation. Cell death index was of 43.5 +/- 12% in
      exposed leaf tissues, 24 h after treatment. In currant tomato protoplasts, the
      percentage of viable cells dropped 1 h after UV-C irradiation from 97.42 +/- 2.1%
      to 43.38 +/- 4.2%. Afterwards, the protoplast viability progressively decreased
      to 40.16 +/- 7.25% at 2 h, to 38.31 +/- 6.9% at 4 h, and to 36.46 +/- 1.84% at 6
      h after the exposure. The genotoxic impact of UV-C radiation on protoplasts was
      assessed with single cell gel electrophoresis (SCGE, or comet assay). UV-C
      treatment greatly enhanced DNA migration, with 75.37 +/- 3.7% of DNA in the tail
      versus 7.88 +/- 5.5% in the case of untreated nuclei. Oxidative stress by
      H(2)O(2) used as a positive control, induced a similar damage on non-irradiated
      protoplasts, with 71.59 +/- 5.5% of DNA in the tail, whereas oxidative stress
      imposed on UV-C irradiated protoplasts slightly increased the DNA damage (85.13
      +/- 4.1%). According to these results, SCGE of protoplasts could be an
      alternative to nuclei extraction directly from leaf tissues.

PMID- 17520090
TI  - Plasma membrane homing of tissue nonspecific alkaline phosphatase under the
      influence of 3-hydrogenkwadaphnin, an antiproliferative agent from Dendrostellera
      lessertii.
AB  - Several mammalian enzymes are anchored to the outer surface of the plasma
      membrane by a covalently attached glycosylphosphatidylinositol (GPI) structure.
      These include acetylcholinesterase, alkaline phosphatase (AP) and 5'-nucleotidase
      among other enzymes. Recently, it has been reported that these membrane enzymes
      can be released into the serum by the GPI-dependent phospholipase D under various
      medical disturbances such as cancer and/or by chemical and physical manipulation
      of the biological systems. Treatment of MCF-7 cells with two consecutive
      effective concentrations of 3-hydrogenkwadaphnin (3-HK, 3 nM) for 48 h enhanced
      membrane AP activity by almost 330% along with a 40% reduction in the AP activity
      of the cell culture medium. In addition, our data indicate that 3-HK is capable
      of inducing mainly the tissue-nonspecific alkaline phosphatase (TNAP) isoenzyme,
      along with enhancing its thermostability. These findings, besides establishing a
      correlation between the antiproliferative activity of 3-HK and the extent of
      plasma membrane AP activity, might assist in the development of new diagnostic
      tools for following cancer medical treatments.

PMID- 17520089
TI  - Kinetic intermediates of unfolding of dimeric prostatic phosphatase.
AB  - Kinetics of guanidine hydrochloride (GdnHCl)-induced unfolding of human prostatic
      acid phosphatase (hPAP), a homodimer of 50 kDa subunit molecular mass was
      investigated with enzyme activity measurements, capacity for binding an external
      hydrophobic probe, 1-anilinonaphtalene-8-sulfonate (ANS), accessibility of thiols
      to reaction with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and 2-(4'
      maleimidylanilino)naphthalene-6-sulfonate (MIANS) and ability to bind Congo red
      dye. Kinetic analysis was performed to describe a possible mechanism of hPAP
      unfolding and dissociation that leads to generation of an inactive monomeric
      intermediate that resembles, in solution of 1.25 M GdnHCl pH 7.5, at 20 degrees
      C, in equilibrium, a molten globule state. The reaction of hPAP inactivation in
      1.25 M GdnHCl followed first order kinetics with the reaction rate constant
      0.0715 +/- 0.0024 min(-1) . The rate constants of similar range were found for
      the pseudo-first-order reactions of ANS and Congo red binding: 0.0366 +/- 0.0018
      min(-1) and 0.0409 +/- 0.0052 min(-1), respectively. Free thiol groups,
      inaccessible in the native protein, were gradually becoming, with the progress of
      unfolding, exposed for the reactions with DTNB and MIANS, with the pseudo-first
      order reaction rate constants 0.327 +/- 0.014 min(-1) and 0.216 +/- 0.010 min(
      1), respectively. The data indicated that in the course of hPAP denaturation
      exposure of thiol groups to reagents took place faster than the enzyme
      inactivation and exposure of the protein hydrophobic surface. This suggested the
      existence of a catalytically active, partially unfolded, but probably dimeric
      kinetic intermediate in the process of hPAP unfolding. On the other hand, the
      protein inactivation was accompanied by exposure of a hydrophobic, ANS-binding
      surface, and with an increased capacity to bind Congo red. Together with previous
      studies these results suggest that the stability of the catalytically active
      conformation of the enzyme depends mainly on the dimeric structure of the native
      hPAP.

PMID- 17520091
TI  - Neuroprotective effects of alpha2-adrenergic receptor agonists.
AB  - Alpha2-adrenergic receptor agonists exert potent analgesic and sedative/hypnotic
      effects. In addition, they have been shown to be neuroprotective in various
      experimental models, but the molecular pathways leading to these actions are
      still poorly defined. This review summarizes the available literature and
      discusses potential mechanisms of alpha2-adrenergic receptor agonist mediated
      neuroprotection.

PMID- 17520093
TI  - The beneficial effects of statins in autoimmune disease therapy.
AB  - Statins, HMG-CoA reductase inhibitors, are widely used for the treatment of
      hypercholesterolemia and the prevention of cardiovascular diseases. Recent
      experimental and clinical studies evaluated the effect of statins on immune and
      inflammatory cells, and the efficacy of statins in treatment of immune diseases.
      This review discusses the roles of statins in the treatment of immune and
      inflammatory diseases.

PMID- 17520092
TI  - NK cell-based cancer immunotherapy.
AB  - The identification of spontaneous antitumor immune responses in cancer patients
      and the demonstration that an intact immune system can prevent against certain
      forms of malignancies invigorated research efforts in the development of cancer
      immunotherapies. To date, numerous and diversified approaches are being
      investigated, thereby providing new means by which to mobilize the cellular and
      molecular elements of the immune system in order to destroy established cancers.
      While it is appreciated that tumor-specific cytotoxic T lymphocytes play a
      critical role in successful immunotherapy, it is becoming increasingly apparent
      that cellular components of both the innate and the adaptive arms of the immune
      system can control tumor growth. In particular, natural killer (NK) cells are
      emerging as key players in the cross-talk between innate and adaptive immunity.
      With the uncovering of the regulatory mechanisms governing NK cell biology, new
      immunotherapies based on the harnessing of NK cell antitumor activity are now
      being developed. In this review, we summarize the role of NK cells in the control
      of tumor growth and discuss potential cancer therapies incorporating NK cell
      mediated antitumor activity.

PMID- 17520094
TI  - Poly(ADP-ribose) polymerase as a drug target for cardiovascular disease and
      cancer: an update.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family
      consisting of PARP-1 and four additional, recently identified poly(ADP
      ribosylating) enzymes. PARP-1 is one of the most abundant nuclear proteins and
      functions as a DNA nick sensor enzyme. Upon binding to DNA breaks, activated PARP
      cleaves NAD+ into nicotinamide and ADP-ribose and polymerizes the latter onto
      nuclear acceptor proteins including histones, transcription factors and PARP
      itself. On one hand, PARP is viewed as a guardian angel of genomic integrity, and
      inhibition of PARP has been used to facilitate the death of tumor cells alone, or
      in combination with antitumor agents. On the other hand, overactivation of PARP
      in response to oxidant- and free radical-mediated excessive DNA single strand
      breaks promotes cell dysfunction and necrotic type cell death in a variety of
      pathophysiological conditions. Pharmacological inhibition of PARP, consequently,
      exerts cytoprotective effects in a variety of diseases including stroke,
      myocardial infarction, heart failure and diabetes mellitus. The research into the
      role of PARP in diabetic cardiovascular injury is now supported by novel tools
      such as new classes of potent inhibitors of PARP as well as genetically
      engineered animals lacking the gene for PARP. In addition, potent PARP inhibitors
      have entered the stage of clinical testing. The current review provides an update
      on the most recent developments in the area of PARP.

PMID- 17520095
TI  - Molecule of the month. Mircera and Daronrix.

PMID- 17520096
TI  - Society for Medicines Research: 40th anniversary symposium.
AB  - The recent symposium of the Society for Medicines Research (SMR), held on
      December 11, 2006, in Westminster, UK, celebrated the 40th anniversary of the
      formation of the SMR. The meeting began with an overview of future strategies for
      medicines research and its funding in Europe. This session was followed by the
      2006 SMR Award lecture, which was given by Dr. Napoleone Ferrara of Genentech,
      for the development of the anti-vascular endothelial growth factor (VEGF)
      antibody bevacizumab for the treatment of cancer. The remainder of the meeting
      showcased the best of medicines research in the United Kingdom by highlighting a
      number of drug discovery success stories from several UK biotech companies, which
      covered the therapeutic areas of central nervous system, cancer and viral
      infection, along with regenerative medicine.

PMID- 17520097
TI  - Latest advances and research in stroke treatment 2007.
AB  - The 32nd International Stroke Conference, held February 7-9, 2007, in San
      Francisco, California, U.S.A., was an excellent forum to bring together advances
      in stroke treatment. Very challenging new steps in the process of developing
      drugs for stroke from basic science to clinical trials, such as testing the in
      vitro efficacy in human tissue of a candidate drug, or its in vivo PET
      distribution in ischemic brain, were proposed. This report focuses on new
      therapeutic stroke targets addressed in the meeting, together with the trends in
      neurovascular research presented at the oral and poster sessions. Some of the
      results obtained by researchers in several stroke fields such as thrombolysis,
      new drugs or devices and nonpharmacological approaches for stroke treatment
      tested in humans will also be covered. From the basic research, promising
      strategies found in new drugs and targets, and endothelial progenitor cells,
      cellular therapies and angiogenesis will be discussed. Also covered in this
      review are a selection of advances introduced in secondary prevention and in
      cerebral hemorrhage.

PMID- 17520098
TI  - Quercetin induces cell cycle G1 arrest through elevating Cdk inhibitors p21 and
      p27 in human hepatoma cell line (HepG2).
AB  - Quercetin is a flavonoid ubiquitously found in nature. The therapeutic effect of
      quercetin on human hepatoma cell line (HepG2) was evaluated in this study.
      Various groups were incubated with different doses of quercetin for 12-, 24-, 48-
      and 72-h time duration and compared with control groups. Dose- and time-dependent
      inhibition in HepG2 proliferation was found with quercetin treatment. At 48 h of
      incubation, 61.78% of the cells were arrested at G(1) phase with 25 microM/l
      quercetin while 89.62% were arrested at G(1) phase with 50 microM/l quercetin.
      Furthermore, the results indicate that quercetin increased the content of Cdk
      inhibitor p21 protein, which was correlated with the elevation in p53 levels
      during 12 h of incubation. In addition, quercetin also increased the level of Cdk
      inhibitor p27 protein during 24 h of incubation. From our results it can be
      concluded that quercetin blocks cell cycle progression at G(1) phase and exerts
      its growth-inhibitory effect through the increase of Cdk inhibitors p21 and p27
      and tumor suppressor p53 in HepG2.

PMID- 17520100
TI  - Opioidergic mechanisms are not involved in the antihyperalgesic effects of
      carbamazepine and oxcarbazepine.
AB  - The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in
      particular the role of opioid receptors, have not been established precisely. The
      systemic effects of naloxone, an opioid receptor antagonist, on the
      antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the
      model of inflammatory hyperalgesia induced by the intraplantar (i.pl.)
      administration of concanavaline A (Con A, 0.8 mg/paw) into the rat hind paw.
      Naloxone (3 mg/kg; i.p.) did not alter the antihyperalgesic effects of either
      carbamazepine or oxcarbazepine. These results indicate that the opioid system of
      pain modulation does not play a significant role in the antihyperalgesic effects
      of carbamazepine and oxcarbazepine.

PMID- 17520099
TI  - Photoprotection by tocopherol submicron emulsion against UV-mediated damage in
      HaCaT cells.
AB  - alpha-Tocopherol is a lipophilic vitamin E that shows antioxidative, antiaging
      and antiphotodamage activity. Nanometer biotechnology is more widely used in the
      entrainment system of drug carriers and the development for new pharmaceutical
      preparations. Ultraviolet irradiation to human skin in the long term can result
      in photoaging and photocarcinogenesis. The purpose of this study was to observe
      the biological features of tocopherol submicron emulsion (vitE SME) and to
      clarify the roles of vitE SME on UVB-induced photodamage in HaCaT keratinocytes
      (KC). VitE SME was prepared by high-pressure homogenization and microemulsion
      technique. HaCaT KC was incubated in the culture medium supplied with 1/200 and
      1/400 of VitE SME prior to different dosages of UVB irradiation. The vitamin E
      amount in the culture medium was measured by high-performance liquid
      chromatography (HPLC). Cell growth and cellular viability was detected by MTT
      assay. The amount of vitamin E remaining in the culture medium significantly
      decreased during the first 8 h, and less than 10% can be detected by the terminal
      experiment (24 h). No cytotoxicity effect of tocopherol NM on HaCat KC was
      observed. In contrast to the control group, the cellular viability of VitE SME
      treated group increased 44.22% by 24 h. Compared with irradiated groups without
      VitE SME, cell proliferation decreased by 17.77% and 40.42% when the HaCaT KC was
      irradiated with 30 mJ/cm(2) and 90 mJ/cm(2) UVB irradiation, respectively. VitE
      SME has no toxicity to cell culture system and is characterized by stable release
      and penetration. Pre-incubation with VitE SME can partly reduce UV-induced cell
      damage, and the photoprotective efficiency to UVB irradiation also shows time
      dependence.

PMID- 17520101
TI  - Antiaggressive effects of topiramate in agonistic encounters between male mice.
AB  - Topiramate, an antiepileptic drug, has been found to be useful for the treatment
      of aggression in clinical populations. However, no studies have explored the
      action of this compound on aggressive behavior in laboratory animals. This work
      examined the effects of topiramate (10, 20, 40 and 80 mg/kg, i.p.) on agonistic
      interactions between male mice, using an ethopharmacological approach.
      Individually housed mice were exposed to anosmic "standard opponents" 30 min
      after drug administration. Ten minutes of diadic interactions were staged between
      a singly housed and an anosmic mouse in a neutral area. The encounters were
      videotaped and the accumulated time allocated by subjects to 10 broad behavioral
      categories was estimated using an ethologically based analysis. Results showed
      that topiramate (20-80 mg/kg) produced a significant reduction of offensive
      behaviors (threat and attack), without affecting immobility. Digging behavior
      (all doses) was also significantly decreased. The antiaggressive effects of
      topiramate could be related to its ability for modulating positively GABA-A
      receptors and/or blocking AMPA subtype of glutamate receptors.

PMID- 17520102
TI  - Pharmacological activity and structural analysis of a benzamide (TKS159) and its
      optical isomers in an in vitro study and in an in vivo study in mice.
AB  - We previously conducted an in vitro study of 4-amino-5-chloro-2-methoxy-N-(1
      ethyl-2-hydroxymethyl-4-pyrrolidinyl)benzamide (2S,4S)-(1, TKS159) and its three
      optical isomers (2S,4R)-(2), (2R,4S)-(3) and (2R,4R)-(4) with respect to their
      binding ability to the 5-HT(4) receptors, as well as an in vivo study on their
      gastric emptying-accelerating ability in rats. Consequently, we reported that
      steric configuration at positions 2 and 4 of the pyrrolidine ring is important in
      determining their pharmacological activity. The optical isomer (2R,4S)-(3)
      exhibited the most potent binding ability. However, the compound (2S,4S)-(1,
      TKS159) exhibited the most potent gastric emptying-accelerating ability in rats.
      A difference was thus found between binding ability and gastric emptying
      accelerating ability in rats. Therefore, we conducted an in vitro study of TKS159
      (1) and its three optical isomers to examine their agonistic activity on the 5
      HT(4) receptors, as well as an in vivo study in mice to examine their gastric
      emptying-accelerating ability. Consequently, a tendency for correlation was found
      between the activity and the ability. TKS159 (1) exhibited the most potent
      pharmacological activity, well reflecting the results from the previous in vivo
      study in rats. Furthermore, the present in vitro and in vivo studies reverified
      the importance of steric configuration at positions 2 and 4 of the pyrrolidine
      ring. In addition, we also made an X-ray crystallographic analysis of the optical
      isomer (2R,4S)-(3), which has the S-configuration at position 4 similar to TKS159
      (1), and discussed molecular structures in conjunction with the previously
      reported results from the X-ray crystallographic analysis of TKS159 (1).

PMID- 17520103
TI  - Effects of MPEP on avoidance learning in rats.
AB  - In recent years metabotropic glutamate receptors (mGluRs) have received
      considerable attention as a potential target for psychotropic drugs, but their
      influence on learning and memory is still unclear. The aim of the present study
      was to examine whether intraperitoneal (i.p.) administration of selective mGluR5
      antagonist 2-methyl-6-(phenylethynyl)-pyrydine (MPEP), injected prior to,
      immediately after or 30 min after training, affects acquisition and/or retrieval
      of the inhibitory step-down and active shuttle-box avoidance in rats. Our results
      indicate that 5 or 10 mg/kg i.p. MPEP in all tested groups impaired memory
      consolidation of step-down training without affecting acquisition and had no
      effect on learning and retention in shuttle-box trained rats. The data are in
      agreement with the statement that mGluR5s may contribute very little and task
      dependently to the actual acquisition of new information, but memory formation,
      appears to require mGluR5s through modulation of consolidation and/or recall.

PMID- 17520104
TI  - Neurochemical changes associated with chronic administration of typical
      antipsychotics and its relationship with tardive dyskinesia.
AB  - The therapeutic success of atypical antipsychotics has focused the attention on
      the role of receptor systems other than dopaminergic system in the
      pathophysiology of neuroleptic-associated extrapyramidal side effects such as
      tardive dyskinesia. In the present study we planned to study time-dependent
      changes in extracellular levels of norepinephrine, dopamine and serotonin in
      cortical and subcortical (including striatum) regions of brain and tried to
      correlate them with hyperkinetic motor activities (vacuous chewing movements
      [VCMs], tongue protrusions and facial jerking) in rats treated chronically with
      typical neuroleptics (haloperidol and chlorpromazine). Chronic administration of
      haloperidol (1 mg/kg) and chlorpromazine (5 mg/kg) resulted in a time-dependent
      increase in orofacial hyperkinetic movements. There were also significant changes
      in the extracellular levels of different neurotransmitters in different brain
      regions (cortical and subcortical regions) as measured by high-performance liquid
      chromatography/electrochemical detection (HPLC/ED). Both haloperidol and
      chlorpromazine produced time-dependent decreases in the levels of these
      neurotransmitters.

PMID- 17520106
TI  - Serum anticholinergic activity in patients following cardiac surgery and healthy
      individuals following amitriptyline application.
AB  - The serum anticholinergic activity (SAA) is used as a marker for cognitive
      impairment. Here, two studies have been performed characterizing the SAA profile.
      In Study 1 the endogenous SAA in relation to the total serum protein
      concentration was monitored for 24 h in five healthy individuals and compared
      with that in four inpatients following cardiac surgery. In Study 2 the SAA of
      seven healthy individuals was assessed following a single amitriptyline dose. In
      both studies SAA was assessed by an ex vivo assay. In Study 1, the absolute SAA
      varied in a wide range of 1.2 and 14.5 atropine equivalents (AEs) over 24 h. A
      circadian pattern was not observed. The mean total serum protein concentration,
      but not the SAA, was significantly lower in inpatients than in healthy
      individuals. In Study 2, the SAA increased following amitriptyline to a maximum.
      The mean SAA increased by 6.39 AE at the amitriptyline peak concentration. High
      SAA variability showed a low statistical relation to amitriptyline
      concentrations. Both studies characterize the SAA as an individual parameter not
      affected per se by surgery or clinical care and poorly correlated with the total
      serum protein concentration. The relation with amitriptyline concentration helps
      to quantify SAA values towards a better understanding of the clinical
      implications and limitations of SAA changes.

PMID- 17520105
TI  - Combination therapy of low-dose atorvastatin and fenofibrate in mixed
      hyperlipidemia.
AB  - Mixed hyperlipidemia is a major cause of coronary artery disease. Monotherapy
      with statins is considered the gold standard for treatment of mixed
      hyperlipidemia. But greater benefit may be expected by combination therapy.
      Combination may allow lower doses of statins and less adverse effects. Hence,
      this preliminary study was designed to evaluate the efficacy and safety of low
      dose atorvastatin in combination with fenofibrate in patients with mixed
      hyperlipidemia. Ninety patients were assigned into three groups and received
      atorvastatin (10-40 mg/day) or fenofibrate (160-200 mg/day) or combination of low
      dose atorvastatin (5 mg/day) and fenofibrate (160 mg/day). There was a
      significant decrease in low-density lipoprotein (LDL), triglycerides (TG) and
      total cholesterol (TC), and a significant increase in high-density lipoprotein
      (HDL) in all the groups at the end of therapy. Combination therapy produced
      maximum decrease in LDL, TG and TC, and maximum increase in HDL when compared
      with monotherapies. No significant difference was reported in safety profile
      between the two groups. To conclude, the results suggest that combination therapy
      with low-dose atorvastatin and fenofibrate is more efficacious, with no increase
      in adverse effects when compared with monotherapies with individual drugs for
      mixed hyperlipidemia. The results are preliminary and suggestive only, as the
      study was open and nonrandomized.

PMID- 17520107
TI  - Gateways to clinical trials.
AB  - 1E10, 101M; AAV-ASPA, agomelatine, aliskiren fumarate, alvimopan hydrate,
      ambrisentan, apaziquone, axitinib; Becatecarin, belagenpumatucel-L, BMS-201038;
      Cannabidiol, Cannabis sativa L. extract, capromorelin, CBP-501, cediranib,
      cetuximab, CHR-2797; Dapoxetine hydrochloride, degarelix acetate, desvenlafaxine
      succinate, dimethyl fumarate, dronedarone hydrochloride; Ecogramostim, eprodisate
      sodium; Falciparum merozoite protein-1/AS02A, fospropofol disodium; Gefitinib,
      glucarpidase, GTI-2040; Hepatitis C vaccine, HMR-4902, human proinsulin C
      peptide, hyaluronic acid; Ipilimumab, ixabepilone; Lapatinib, lenalidomide,
      lestaurtinib, liposome encapsulated doxorubicin; Manidipine
      hydrochloride/delapril hydrochloride, metreleptin, MG-98, MGCD-0103, morphine
      glucuronide; Nebicapone; O6-benzylguanine, ofatumumab, olmesartan
      medoxomil/hydrochlorothiazide; PAN-811, pemetrexed disodium, perifosine,
      pertuzumab, Peru-15, pexelizumab, pirfenidone, pralatrexate, prasugrel;
      Quercetin; Rivaroxaban; Semaxanib, St. John's Wort extract; Ticagrelor,
      tomopenem, triplatin tetranitrate; Ulipristal acetate; Vandetanib, vatalanib
      succinate, vildagliptin; XK-469; ZT-1.

PMID- 17520108
TI  - Novel synthetic strategies for the preparation of prostacyclin and prostaglandin
      analogues--off the beaten track.
AB  - The recent increase in activity in the fields of neuroscience and life sciences
      has been mirrored by the design and synthesis of novel chemically and
      metabolically stable prostaglandin and prostacyclin analogues. Consequently,
      convenient and practical access to these important classes of compounds is
      greatly coveted. Various strategies for the preparation of prostacyclin,
      prostaglandin and isoprostane analogues are discussed, with particular focus on
      novel approaches developed in our own laboratories.

PMID- 17520109
TI  - Isophthalamides and 2,6-dicarboxamidopyridines with pendant indole groups: a
      'twisted' binding mode for selective fluoride recognition.
AB  - Two cleft-like anion receptors have been synthesised that contain indole hydrogen
      bond donors and show fluoride selectively in a DMSO-water solution with
      crystallographic studies showing a 'twisted' binding mode for fluoride in the
      solid state.

PMID- 17520110
TI  - Enantioselectivity in the boron aldol reactions of methyl ketones.
AB  - DFT computed transition states quantitatively explain the surprising
      stereochemical outcome of unsubstituted enolborinates in diastereoselective and
      enantioselective boron aldol reactions.

PMID- 17520111
TI  - Hydroxy-cruciforms.
AB  - The synthesis of hydroxy-cruciforms 7 and 8 and their dramatically varying
      photophysical properties upon exposure to amines are reported.

PMID- 17520112
TI  - Ultrafast IR spectroscopy of the short-lived transients formed by UV excitation
      of cytosine derivatives.
AB  - A strong infrared band at 1574 cm(-1) is observed following 267 nm excitation of
      2'-deoxycytidine (tau = 37 +/- 4 ps) or 2'-deoxycytidine 5'-monophosphate (tau =
      33 +/- 4 ps); this band is provisionally attributed to an 1n(N)pi* state and is
      absent for cytosine.

PMID- 17520113
TI  - Dual-labeled oligonucleotide probe for sensing adenosine via FRET: a novel
      alternative to SNPs genotyping.
AB  - A novel FRET based strategy for DNA sequence analysis utilising base
      discriminating fluorescence (BDF) nucleoside, (Py)U/(2-Ant)U, as donor in the
      dual-labelled oligonucleotide probe is reported; a selective/specific emission
      from acceptor, was observed upon excitation at the donor, only when the opposite
      base of the "smart" fluorescently labeled BDF nucleoside, (Py)U/(2-Ant)U, is
      adenine on the complementary target sequence.

PMID- 17520114
TI  - Poly(vinyl alcohol)-graft-poly(ethylene glycol) resins and their use in solid
      phase synthesis and supported TEMPO catalysis.
AB  - New poly(vinyl alcohol)-graft-poly(ethylene glycol) (PVA-g-PEG) resins with
      various PEG chain lengths, which have high loadings and good swelling both in
      water and organic solvents, have been prepared via an anionic polymerization of
      ethylene oxide onto PVA beads and applied in solid-phase synthesis, supported
      TEMPO catalysis and in HR-MAS 1H NMR spectral analysis.

PMID- 17520115
TI  - Design and preparation of bioactive glasses with hierarchical pore networks.
AB  - Hierarchically giant-, macro-, and meso-porous 3D bioactive glass scaffolds with
      good bone-forming bioactivity in vitro were synthesized by using a combination of
      sol-gel, double polymers templating, and rapid prototyping techniques.

PMID- 17520116
TI  - Detection of explosives on skin using ambient ionization mass spectrometry.
AB  - Single nanogram amounts of the explosives TNT, RDX, HMX, PETN and their mixtures
      were detected and identified in a few seconds on the surface of human skin
      without any sample preparation by desorption electrospray ionization (DESI) using
      a spray solution of methanol-water doped with sodium chloride to form the
      chloride adducts with RDX, HMX, and PETN while TNT was examined as the radical
      anion and tandem mass spectrometry was used to confirm the identifications.

PMID- 17520117
TI  - Ultra-fast microwave enhanced reversible addition-fragmentation chain transfer
      (RAFT) polymerization: monomers to polymers in minutes.
AB  - Microwave mediated RAFT polymerization leads to ultra-fast polymerizations,
      whilst keeping excellent control over molecular weights and molecular weight
      distributions; this is the first example of such a dramatic effect of microwaves
      on living radical polymerization kinetics, and it shows the potential for
      chemists to produce very well controlled polymers in a matter of minutes.

PMID- 17520118
TI  - Synthesis and structural characterisation of the first N-heterocyclic carbene
      ligand fused to a porphyrin.
AB  - The functionalisation of two neighboring beta-pyrrolic positions of a porphyrin
      by a fused N-heterocyclic carbene ligand, the subsequent metallation of this
      external coordination site by palladium(II) and the structural characterisation
      of the resulting compounds are presented.

PMID- 17520119
TI  - Total synthesis of (-)-conocarpan and assignment of the absolute configuration by
      chemical methods.
AB  - (-)-Conocarpan (1) was synthesized by a method based on radical cyclization, and
      the absolute configuration was established by chemical degradation; the original
      2R,3R-assignment to (+)-conocarpan should be reversed, as suggested by a later
      chiroptical study of model 2,3-dihydrobenzofurans.

PMID- 17520120
TI  - Lewis acidity enhancement of organoboranes via oxidation of appended ferrocene
      moieties.
AB  - The Lewis acidity of boron in diboradiferrocene 1 is strongly enhanced through
      oxidation of the iron atoms as evident from examination of X-ray structural
      parameters of the mixed-valent cation 1(+)PF(6) and further confirmed from the
      strong complexation of MeCN to the dication in 2(2+)(I(3))(2).

PMID- 17520121
TI  - Non-nanogold catalyzed aerobic oxidation of secondary amines to imines.
AB  - Bulk gold powder (approximately 10(3) nm particle size) is a highly active
      catalyst for the oxidative dehydrogenation of secondary amines to imines under
      the mild conditions of 1 atm O2 and 60-100 degrees C.

PMID- 17520122
TI  - Unprecedented optically induced long-lived intramolecular electron transfer in
      cobalt-dioxolene complexes.
AB  - The observation of very long lifetimes of the metastable states of two cobalt
      dioxolene complexes undergoing photoinduced and high T(c) thermally-induced
      valence tautomer interconversion opens new research perspectives.

PMID- 17520123
TI  - Stereochemistry of rHint1 hydrolase assisted cleavage of P-N bond in nucleoside
      5'-O-phosphoramidothioates.
AB  - The Hint-1 hydrolase assisted cleavage of the P-N bond in adenosine-5'-O-[N
      (tryptophanylamide)]phosphoramidothioate proceeds with retention of configuration
      at the phosphorus atom which is consistent with the formation of a covalent
      enzyme-substrate complex.

PMID- 17520124
TI  - A2B2-type push-pull porphyrins as reverse saturable and saturable absorbers.
AB  - A(2)B(2)-type push-pull porphyrins with a strong intramolecular dipole moment
      have been prepared via Heck and Suzuki coupling reactions as novel materials for
      use in nonlinear optics (NLO); they display saturable (SA) and reverse saturable
      absorption (RSA) properties at 532 nm and their nonlinear optical response is
      characterized by RSA occurring at lower intensity levels whereas the onset of SA
      prevails at higher levels.

PMID- 17520125
TI  - A chronocoulometric aptamer sensor for adenosine monophosphate.
AB  - The selective recognition of adenosine monophosphate by a half-duplex aptamer
      modified electrode leads to a simple chronocoulometric aptasensor based on the
      changes in surface charges.

PMID- 17520126
TI  - Selective oxidation of methanol to dimethoxymethane under mild conditions over
      V2O5/TiO2 with enhanced surface acidity.
AB  - Dimethoxymethane was synthesized from the direct oxidation of methanol with high
      conversion and selectivity over specially designed bifunctional V(2)O(5)/TiO2
      catalysts with redox and enhanced acidic character, in which the surface acidity
      played an essential role for inhibiting the formation of formaldehyde through the
      enhanced condensation reaction of formaldehyde with methanol to produce
      dimethoxymethane.

PMID- 17520127
TI  - A tricarbonyl rhenium(I) complex with a pendant pyrrolidinium moiety as a robust
      and recyclable catalyst for chemical fixation of carbon dioxide in ionic liquid.
AB  - A novel Re(I) complex covalently anchored with a pyrrolidinium moiety was
      successfully synthesized and used as an efficient and recyclable catalyst in the
      cycloaddition of CO2 with epoxides under mild reaction conditions to give
      excellent isolated yield and selectivity of cyclic carbonates in pyrrolidinium
      ionic liquid.

PMID- 17520128
TI  - Unexpectedly facile isomerisation of [7,10-Ph2-7,10-nido-C2B10H10]2- to [7,9-Ph2
      7,9-nido-C2B10H10]2-.
AB  - The 2e-reduction of 1,12-Ph2-1,12-closo-C(2)B(10)H(10) followed by oxidation or
      metallation gives products that arise from [7,9-Ph2-7,9-nido-C(2)B(10)H(10)](2-),
      formed by unexpectedly facile isomerisation of the kinetic 7,10-isomer: the 4,1,6
      MC(2)B(10) compounds which result are progressively isomerised to 4,1,8- and
      4,1,12-isomers for M = {CpCo} but to an equilibrium mixture of 4,1,8- and 4,1,12
      isomers for M = {(arene)Ru}.

PMID- 17520129
TI  - CILAT--a new reagent for quantitative proteomics.
AB  - We report the development of a new reagent, called CILAT (Cleavable Isobaric
      Labeled Affinity Tag), for quantitative proteomics, which represents an
      improvement over current ICAT (Isotope-Coded Affinity Tag) and iTRAQ (Isobaric
      Tags for Relative and Absolute Quantitation) methods.

PMID- 17520130
TI  - The active role of NHC ligands in platinum-mediated tandem hydroboration-cross
      coupling reactions.
AB  - Stable N-heterocyclic platinum-carbene complexes are the first example of
      platinum-mediated regioselective H-B addition to vinylarenes and alkynes,
      allowing consecutive cross coupling reactions with the same catalytic system.

PMID- 17520131
TI  - Factors influencing the selectivity in asymmetric oxidation of sulfides attached
      to nitrogen containing heterocycles.
AB  - Asymmetric oxidation of heterocyclic sulfides, including imidazole,
      benzimidazole, indole and pyrimidine derivatives, were studied using a
      tartrate/Ti((i)OPr)4 catalyst system.

PMID- 17520132
TI  - Synthesis and structural characterization of lanthanide complexes with the di- or
      tri-anionic diguanidinate ligand: new insight into the flexibility and distinct
      reactivity of the linked diguanidinate ligand.
AB  - Unprecedented disproportionation and deprotonation of the linked diguanidinate
      ligand have been established, demonstrating, for the first time, that the number
      and distribution of negative charges on the diguanidinate ligand are tunable, and
      representing a new and efficient method for synthesis of linked diguanidinate di-
      and tri-anion complexes.

PMID- 17520133
TI  - Molecular rotors--fluorescent biosensors for viscosity and flow.
AB  - Viscosity is a measure of the resistance of a fluid against gradients in flow
      (shear rate). Both flow and viscosity play an important role in all biological
      systems from the microscopic (e.g., cellular) to the systemic level. Many methods
      to measure viscosity and flow have drawbacks, such as the tedious and time
      consuming measurement process, expensive instrumentation, or the restriction to
      bulk sample sizes. Fluorescent environment-sensitive dyes are known to show high
      sensitivity and high spatial and temporal resolution. Molecular rotors are a
      group of fluorescent molecules that form twisted intramolecular charge transfer
      (TICT) states upon photoexcitation and therefore exhibit two competing
      deexcitation pathways: fluorescence emission and non-radiative deexcitation from
      the TICT state. Since TICT formation is viscosity-dependent, the emission
      intensity of molecular rotors depends on the solvent's viscosity. Furthermore,
      shear-stress dependency of the emission intensity was recently described.
      Although the photophysical processes are widely explored, the practical
      application of molecular rotors as sensors for viscosity and the fluid flow
      introduce additional challenges. Intensity-based measurements are influenced by
      fluid optical properties and dye concentration, and solvent-dye interaction
      requires calibration of the measurement system to a specific solvent. Ratiometric
      dyes and measurement systems help solve these challenges. In addition, the
      combination of molecular rotors with specific recognition groups allows them to
      target specific sites, for example the cell membrane or cytoplasm. Molecular
      rotors are therefore emerging as new biosensors for both bulk and local
      microviscosity, and for flow and fluid shear stress on a microscopic scale and
      with real-time response.

PMID- 17520134
TI  - Artificial photosynthetic systems: assemblies of slipped cofacial porphyrins and
      phthalocyanines showing strong electronic coupling.
AB  - This paper reviews selected types of structurally well defined assemblies of
      porphyrins and phthalocyanines with strong electronic coupling. Face-to-face,
      head-to-tail, slipped cofacial, and non-parallel dimeric motifs constructed by
      covalent and non-covalent bonds are compared in the earlier sections. Their
      molecular orientation, electronic overlap, and absorption and fluorescence
      properties are discussed with a view towards the development of artificial
      photosynthetic systems and molecular electronics. Complementary coordination
      dimers are fully satisfactory in terms of structural stability, orientation
      factor, pi-electronic overlap, and zero fluorescence quenching. In later
      sections, several polymeric and macrocyclic porphyrin assemblies constructed by a
      combination of covalent bonds and complementary coordination bonds are discussed
      from the viewpoint of light-harvesting antenna functions.

PMID- 17520135
TI  - Formation of an aminoacyl-S-enzyme intermediate is a key step in the biosynthesis
      of chloramphenicol.
AB  - Herein we report the first biochemical characterization of an enzyme involved in
      the biosynthesis of chloramphenicol that provides new insights into the origins
      of the antibiotic.

PMID- 17520136
TI  - Synthesis of bitriazolyl nucleosides and unexpectedly different reactivity of
      azidotriazole nucleoside isomers in the Huisgen reaction.
AB  - Novel bitriazolyl nucleosides were synthesized via the Huisgen reaction, starting
      with 3-azidotriazole nucleoside (1). Surprisingly, its isomer, 5-azidotriazole
      nucleoside (1') did not yield the corresponding Huisgen reaction products
      efficiently because it was rapidly reduced to amine in the presence of Cu(II)
      ascorbate. The significant differences between the reactivity of these two
      isomers in Cu(II)-ascorbate mediated reactions are mainly due to differences in
      their electronic properties and steric congestion as a result of different
      relative positions of the azido and the ribosyl moieties.

PMID- 17520137
TI  - Epicoccarines A, B and epipyridone: tetramic acids and pyridone alkaloids from an
      Epicoccum sp. associated with the tree fungus Pholiota squarrosa.
AB  - Investigation of the metabolic profile of a fungus (Epicoccum sp.) isolated from
      the fruiting body of the tree fungus Pholiota squarrosa led to the discovery of
      two novel tetramic acid derivatives, epicoccarine A (2) and B (3), as well as a
      new pyridone alkaloid, epipyridone (1), with an unusually cyclized side chain. It
      appears that 1 is biogenetically derived from the ring expansion of 2 followed by
      a proposed hetero-Diels-Alder reaction. 2 shows selective antibacterial activity
      against Gram positive bacteria, in particular Mycobacterium vaccae.

PMID- 17520138
TI  - Carboxylate binding in polar solvents using pyridylguanidinium salts.
AB  - A series of thiourea and guanidinium derivatives have been prepared and their
      ability to bind a carboxylate group has been investigated. Guanidinium 33,
      featuring two additional amides and a pyridine moiety, proved to be the most
      potent carboxylate binding site and was able to bind acetate in aqueous solvent
      systems (K(ass) = 480 M(-1) in 30% H(2)O-DMSO). The pyridine moiety is critical
      to obtaining strong binding, and comparison with the binding properties of
      analogous compounds in which the pyridine is replaced by a benzene ring provides
      a striking example of enthalpy-entropy compensation.

PMID- 17520139
TI  - Microbial Baeyer-Villiger oxidation of terpenones by recombinant whole-cell
      biocatalysts--formation of enantiocomplementary regioisomeric lactones.
AB  - Recombinant whole-cell expression systems for Baeyer-Villiger monooxygenases of
      various bacterial origin were utilized in the regiodivergent biooxidation of
      cyclic terpenones enabling access to enantio- and regioisomeric lactones on
      preparative scale.

PMID- 17520140
TI  - "O-acyl isopeptide method" for peptide synthesis: synthesis of forty kinds of "O
      acyl isodipeptide unit" Boc-Ser/Thr(Fmoc-Xaa)-OH.
AB  - The O-acyl isopeptide method has recently received attention as an efficient
      synthetic method for peptides. Herein, forty kinds of "O-acyl isodipeptide unit"
      Boc-Ser/Thr(Fmoc-Xaa)-OH (1-40) were effectively synthesized in two-steps without
      epimerization. The O-acyl isodipeptide units are important building blocks to
      enable the routine use of the O-acyl isopeptide method.

PMID- 17520141
TI  - A potent bicyclic inhibitor of a family 27 alpha-galactosidase.
AB  - Two isomeric bicyclo[4.1.0]heptane analogues of the glycosidase inhibitor galacto
      validamine, (1R*,2S,3S,4S,5S,6S*)-5-amino-1-(hydroxymethyl)bicyclo[4.1.0]heptane
      2,3,4-triol, have been synthesized in 13 steps from 2,3,4,6-tetra-O-benzyl-D
      galactose. The inhibitory activities of the two conformationally restricted
      amines, and their corresponding acetamides, were measured against commercial
      alpha-galactosidase enzymes from coffee bean and E. coli. The activity of the
      glycosyl hydrolase family GH27 enzyme (coffee bean) was competitively inhibited
      by the 1R,6S-amine (7), a binding interaction that was characterized by a K(i)
      value of 0.541 microM. The GH36 E. coli alpha-galactosidase exhibited a much
      weaker binding interaction with the 1R,6S-amine (IC(50)= 80 microM). The
      diastereomeric 1S,6R-amine (9) bound weakly to both galactosidases, (coffee bean,
      IC(50)= 286 microM) and (E. coli, IC(50)= 2.46 mM).

PMID- 17520142
TI  - Calculation of the relative acidities and oxidation potentials of para
      substituted phenols. A model for alpha-tocopherol in solution.
AB  - Relative acidities (Delta pK(a)) of phenols and oxidation potentials (Delta
      E(ox)) of the phenoxide anions have been calculated for nine para-substituted
      phenols using density functional theory. Solvent effects were incorporated using
      the conductor-like polarisable continuum method. Using the calculated Delta pK(a)
      and Delta E(ox) values in a thermodynamic cycle, the DeltaBDE (bond dissociation
      enthalpy) of the phenols were also determined with all values calculated to
      within 1.5 kcal mol(-1) of experiment. The Delta pK(a) and Delta E(ox) values
      were calculated for 6-hydroxy-2,2,5,7,8-pentamethylchroman (HPMC), a model for
      alpha-tocopherol for which there are no known experimental values. The acidity of
      this compound is raised by 2.4 pK(a) units and lowered by -0.79 V relative to
      phenol with a calculated Delta BDE of -14.9 kcal mol(-1). There is a negative
      correlation (r(2) = 0.86) between the Delta pK(a) and the Delta BDE values. A
      stronger and positive correlation is found between the Delta E(ox) (r(2) = 0.98)
      and the Delta BDE values. Using these correlations it is uncovered that hydrogen
      abstraction of phenols, as measured by the Delta BDE, is driven by electron
      transfer rather than by proton transfer.

PMID- 17520143
TI  - Mayr electrophilicity predicts the dual Diels-Alder and sigma-adduct formation
      behaviour of heteroaromatic super-electrophiles.
AB  - We report on the dual reactivity, i.e. anionic Meisenheimer sigma adduct
      formation and Diels-Alder adduct formation, of a series of heteroaromatic super
      electrophiles, including 4,6-dinitro-benzofuroxan, -N-arylbenzotriazoles (4), 
      benzothiadiazole and -benzoselenadiazole. Measured pK(a)(H(2)O) values for sigma
      adduct formation provide a quantitative measure of super-electrophilic reactivity
      with a satisfactory correlation between the Mayr E electrophilicity parameter and
      pK(a)(H(2)O): E = -0.662 pK(a)(H(2)O) (or pK(R+) -3.20 (r(2) = 0.987). The most
      highly electrophilic, pre-eminent super-electrophile is 4,6
      dinitrotetrazolopyridine (E = -4.67, pK(a)(H(2)O) = 0.4), which supercedes the
      reference Meisenheimer super-electrophile, 4,6-dinitrobenzofuroxan (E = -5.06,
      pK(a) = 3.75), having itself an E value superior by 8 orders of magnitude
      compared to 1,3,5-trinitrobenzene as the benchmark normal Meisenheimer
      electrophile (E = -13.19, pK(a)(H(2)O) = 13.43). (For relevant kinetic parameters
      as well as E and pK(a) values, see .) In a parallel study we have investigated
      Diels-Alder (normal and inverse electron demand) reactivity of this series of
      heteroaromatic electrophiles and have shown that Mayr E values are valid
      predictors of whether DA adducts will form and how rapidly. The observed order of
      pericyclic reactivity corresponds to E = -8.5 as the demarcation E value, in
      close agreement with sigma complexation; thus pointing to a common origin for the
      two processes, i.e. an inverse relationship between the degree of aromaticity of
      the carbocyclic ring and ease of sigma complexation, or DA reactivity,
      respectively.

PMID- 17520144
TI  - Towards a general solid phase approach for the iterative synthesis of conjugated
      oligomers using a germanium based linker--first solid phase synthesis of an oligo
      (triarylamine).
AB  - The development of a germanium-based linker system for the solid phase synthesis
      (SPS) of 3-(n-hexyl)thiophene oligomers and the first SPS of triarylamine
      oligomers via iterative chain extension is described. The efficiency of the key
      steps in the oligomer syntheses and their compatibility with the germanium linker
      are demonstrated by the SPS of bi-[3-(n-hexyl)thiophene] 19 and ter
      (triarylamine) 50. The use of a germanium-based linker in combination with
      appropriately selected silicon-based blocking/protecting groups allows double
      coupling to drive the key cross coupling steps to completion hence minimising
      deletion sequences and also allows for traceless and potentially
      functionalisative cleavage from the resin. The latter feature has yet to be fully
      explored but towards this end the first ipso-borodegermylation reaction of a 2
      germyl-3-(n-hexyl)thiophene is presented.

PMID- 17520145
TI  - Exploring enzymatic catalysis at a solid surface: a case study with
      transglutaminase-mediated protein immobilization.
AB  - The factors affecting enzymatic protein immobilization with microbial
      transglutaminase (MTG) were explored. As model proteins, enhanced green
      fluorescent protein (EGFP) and glutathione S-transferase (GST) were chosen and
      tagged with a neutral Gln-donor substrate peptide for MTG (Leu-Leu-Gln-Gly, LLQG
      tag) at their C-terminus. To create a specific surface, displaying reactive Lys
      residues, to be cross-linked with the Gln residue in the LLQG-tag of target
      proteins by MTG catalysis, a polystyrene surface was physically coated with beta
      casein. Both recombinant proteins were immobilized onto the beta-casein-coated
      surface only in the presence of active MTG, indicating that those proteins were
      enzymatically immobilized to the surface. MTG-mediated protein immobilization
      markedly depends on the pH and ionic strength of the reaction media. The optimal
      pH range of MTG-mediated immobilization of both recombinant proteins was around
      5, at which point the MTG-catalyzed reaction in aqueous solution is not normally
      preferred. By utilizing a pH-dependent change in EGFP fluorescence, we found that
      the apparent pH at the surface is likely to be lower than bulk pH, this
      difference is not attributed to an optimal pH shift in MTG-mediated
      immobilization. On the other hand, lower yields of protein immobilization at
      higher ionic strength suggest that electrostatic interaction is a key factor
      governing MTG catalysis at a solid surface. The results of this study indicate
      that, in enzymatic catalysis at a solid surface, the concentration of substrates
      at the surface can enhance the catalytic efficiency, and this could alter the pH
      dependence of enzymatic catalysis.

PMID- 17520146
TI  - N-amidothiourea based PET chemosensors for anions.
AB  - Neutral N-amidothiourea based PET anion sensors bearing a pyrene fluorophore, 1
      3, were synthesized and their fluorescent response toward anions was assessed.
      The anion quenching and binding constants were found to be much higher than those
      of the corresponding PET sensors bearing a simple thiourea receptor despite a
      higher oxidation potential of the electron donor and a relatively longer spacer
      (CH(2))(3) between the signal reporter and binding receptor in 1-3. This was
      explained in terms of a much more substantial increase in the electron donating
      ability of amidothiourea upon anion binding.

PMID- 17520147
TI  - Cascade radical-mediated cyclisations with conjugated ynone electrophores. An
      approach to the synthesis of steroids and other novel ring-fused polycyclic
      carbocycles.
AB  - A cascade radical-mediated Diels-Alder reaction with the iododienynone 16b
      produced the tricyclic ketone 17 (22%). By contrast, treatment of the substituted
      furans 36 and 47 with Bu(3)SnH-AIBN, instead led to the tetracycles 44 and 58
      respectively, rather than the anticipated oestranes, i.e. 38 and 48. In a
      separate study, attempted cascade radical-mediated cyclisations from the ortho
      aryl substituted iododienynones 72 and 73, leading to the ring-D aromatic steroid
      7, instead gave the macrocyclic ketone 76 or the novel bridged tricycles 77/82,
      respectively, depending on whether benzene or heptane was used as solvent in the
      reactions.

PMID- 17520148
TI  - Synthesis of a chiral amino acid with bicyclo[1.1.1]pentane moiety and its
      incorporation into linear and cyclic antimicrobial peptides.
AB  - The synthesis of the lipophilic chiral amino acid 1 bearing the
      bicyclo[1.1.1]pentane moiety is described. Linear and cyclic hexapeptides of the
      type Arg-Arg-Xaa-Yaa-Arg-Phe containing 1 instead of one or two tryptophan
      residues are prepared by solid phase peptide synthesis and the antimicrobial and
      hemolytic activity of the peptides obtained are discussed.

PMID- 17520149
TI  - Indole as a scaffold for anion recognition.
AB  - Indole has an acidic N-H that can be used to form hydrogen bonds to anions and in
      this paper the synthesis of three new suitably functionalised indole based anion
      receptors is presented along with their evaluation using (1)H NMR titration
      techniques.

PMID- 17520150
TI  - Epoxidation-alcoholysis of cyclic enol ethers catalyzed by Ti(OiPr)4 or
      Venturello's peroxophosphotungstate complex.
AB  - Venturello's peroxophosphotungstate compound and Ti(O(i)Pr)(4) were successfully
      used as catalysts for the epoxidation-alcoholysis of various dihydropyrans and
      dihydrofuran using H(2)O(2) as the oxidant. Different alcohols can be used as
      solvents and nucleophiles, resulting in hydroxy ether products with varying
      alkoxy groups. The Venturello compound can also be used as catalyst in a biphasic
      conversion of dihydropyran, in which long chain alcohols or fatty acids are
      incorporated in the hydroxy ether products with high yield and
      (stereo)selectivity.

PMID- 17520151
TI  - Wool peptide derivatives for hand care.
AB  - Hands experience much greater wear and tear during normal daily routines compared
      with most other parts of the body, and thereby demand specific needs from
      cosmetics targeted at hand care. Keratin proteins are the major structural
      component of the outer layers of the skin. In this work a novel keratin fraction
      from wool, which has high cystine content present in the S-sulphonated form, has
      been developed to target hand care applications. In vivo long-term studies were
      performed to evaluate the water-holding capacity and elasticity of hand skin
      following topical application of keratins. Moreover, protection of healthy skin
      against detergent-induced dermatitis was evaluated after topical application of
      the keratin-active formulation. Significant results in the measured biophysical
      parameters were found, which indicated an improvement in the skin's water-holding
      capacity, hydration, and elasticity for volunteers with dry skin as a result of
      the keratin peptide treatment. Results also indicated that the keratin peptide
      treatment can prevent some of the damaging effects associated with surfactant
      exposure.

PMID- 17520152
TI  - The role of sodium dodecyl sulfate (SDS) micelles in inducing skin barrier
      perturbation in the presence of glycerol.
AB  - The stratum corneum (SC) serves as the skin barrier between the body and the
      environment. When the skin is contacted with an aqueous solution of the
      surfactant sodium dodecyl sulfate (SDS), a well-known model skin irritant, SDS
      penetrates into the skin and disrupts this barrier. It is well established, both
      in vitro and in vivo, that the SDS skin penetration is dose-dependent, and that
      it increases with an increase in the total SDS concentration above the critical
      micelle concentration (CMC) of SDS. However, when we added the humectant glycerol
      at a concentration of 10 wt% to the aqueous SDS contacting solution, we observed,
      through in vitro quantitative skin radioactivity assays using (14)C-radiolabeled
      SDS, that the dose dependence in SDS skin penetration is almost completely
      eliminated. To rationalize this important observation, which may also be related
      to the well-known beneficial effects of glycerol on skin barrier perturbation in
      vivo, we hypothesize that the addition of 10 wt% glycerol may hinder the ability
      of the SDS micelles to penetrate into the skin barrier through aqueous pores that
      exist in the SC. To test this hypothesis, we conducted mannitol skin permeability
      as well as average skin electrical resistivity measurements in vitro upon
      exposure of the skin to an aqueous SDS contacting solution and to an aqueous SDS
      + 10 wt% glycerol contacting solution in the context of a hindered-transport
      aqueous porous pathway model of the SC. Our in vitro studies demonstrated that
      the addition of 10 wt% glycerol: (i) reduces the average aqueous pore radius
      resulting from exposure of the skin to the aqueous SDS contacting solution from
      33 +/- 5 Angstrom to 20 +/- 5 Angstrom, such that a SDS micelle of radius 18.5 +/
      1 Angstrom (as determined using dynamic light-scattering measurements)
      experiences significant steric hindrance and cannot penetrate into the SC, and
      (ii) reduces the number density of aqueous pores in the SC by more than 50%,
      thereby further reducing the ability of the SDS micelles to penetrate into the SC
      and perturb the skin barrier.

PMID- 17520153
TI  - Effect of oil films on moisture vapor absorption on human hair.
AB  - In this paper sorption and desorption of water vapor on hair fibers treated with
      various oils is investigated, using a dynamic vapor sorption (DVS) apparatus.
      Results show lower "equilibrium" sorption of moisture for various oil-treated
      samples compared to the untreated sample. Coconut oil-treated hair had a higher
      regain than mineral oil-treated hair. Although treating the hair samples with oil
      reduced moisture pickup, a considerable amount of moisture vapor was still able
      to penetrate into hair fibers. Calculated hysteresis plots show that the samples
      treated with different oils have slightly higher moisture retention at low
      relative humidities compared to that of the untreated sample, which suggests a
      beneficial effect. The calculated moisture diffusion coefficients for oil-treated
      samples were much lower compared to the untreated hair fibers, suggesting that
      surface oil films and penetrated oil molecules form a diffusion barrier. A
      moisture diffusion model is discussed in terms of the possible role of fiber
      swelling on restrictive narrowing of the cell membrane complexes (CMCs), which
      form the diffusion pathways in the fiber. The effect of film thickness on
      moisture absorption and the reverting of the sorption isotherm to that of the
      untreated hair after removal of the oil film shows that oil film is the main
      resistance to moisture diffusion. The lowering of the diffusion coefficient of
      water vapor by oil films will slow the loss of moisture, an effect similar to
      "moisturization" of hair.

PMID- 17520155
TI  - Preparation and stability of cosmetic formulations with an anti-aging peptide.
AB  - Wrinkling of the skin is the most obvious sign of deterioration of the human body
      with age. This process involves a number of genetic, constitutional, hormonal,
      nutritional, and environmental factors, in addition to the influence of
      frequently repeated facial movements during laughing, smoking, etc. This article
      reviews the physiological basis and mechanism of action of the active cosmetic
      ingredient acetyl hexapeptide-8 (Argireline). We prepared two formulations: an
      emulsion with an external aqueous phase for normal to dry skin, and a gel for
      oily skin. Laboratory analyses, rheology tests and in vitro release assays were
      used to evaluate the stability of these formulations for cosmetic treatment.

PMID- 17520154
TI  - Formulation, characterization, and efficacy of an adenosine-containing
      dissolvable film for a localized anti-wrinkle effect.
AB  - A water-dissolvable film was developed to topically deliver adenosine for a
      localized anti-wrinkle effect. The polymers used to produce the film were
      cellulose derivatives. An aqueous mixture of the film components was made, coated
      on a liner, and then dried to form a solid film. No preservatives were added and
      the film was shown to be stable over time. The film quickly dissolves in water to
      form a uniform layer at the surface of the skin, as shown by scanning electron
      microscopy. The film layer can still be visualized on the wrinkle six hours after
      being applied on the skin. A randomized, placebo-controlled, investigator-blind
      study was conducted in female volunteers to assess the efficacy of the 1%
      adenosine-containing dissolvable film. After three weeks and eight weeks, a twice
      daily application led to a significant decrease in the skin roughness parameters
      as observed using fast optical in vivo topometry (FOITS). These results
      demonstrate that water-dissolvable films may be used as novel, preservative-free,
      cosmetic delivery systems.

PMID- 17520160
TI  - Social support among veterans with serious mental illness.
AB  - BACKGROUND: We determined whether patients with serious mental illness were more
      likely to report low social support than those without serious mental illness.
      METHOD: We conducted a national, cross-sectional study of VA patients in Fiscal
      Year 1999 who were diagnosed with a serious mental illness, as well as a random
      sample of VA patients without a diagnosis of serious mental illness (N = 8,547)
      from the National Psychosis Registry who also completed the VA's Large Health
      Survey of Veteran Enrollees (LHSV) 9-item questionnaire on social support. Using
      generalized estimating equations; we assessed patient's likelihood of reporting
      low social support, while controlling for patient socio-economic and clinical
      factors. RESULTS: In multivariable models adjusting for patient factors, patients
      with serious mental illness were more likely to report low instrumental support,
      e.g., having no one to help with chores (OR = 1.41, p < 0.001) and low emotional
      support, e.g., having no one to relax with (OR = 2.05, p < 0.001). CONCLUSIONS:
      Patients diagnosed with serious mental illness reported low social support across
      different dimensions. Recovery-oriented services for persons with serious mental
      illness should focus on improving and sustaining emotional and instrumental
      supports for this vulnerable population.

PMID- 17520161
TI  - Age variation in life events and their relationship with common mental disorders
      in a national survey population.
AB  - BACKGROUND: Life events (LEs) are recognised to be important risk factors for
      common mental disorders (CMD). Their prominence may vary across age groups but
      this issue has received little systematic investigation. METHOD: Data were
      analysed from the 2000 UK National Survey of Psychiatric Morbidity comprising
      8,580 participants aged 16-74 years. A history of recent life events pertaining
      to health threats, bereavement, interpersonal problems and redundancy was
      established for the preceding six months. Participants were also asked about
      earlier lifetime stressors including sexual abuse and expulsion from school. CMD,
      depression and generalised anxiety disorder were ascertained through the revised
      Clinical Interview Schedule. RESULTS: The strongest associations between LEs and
      CMD were for recent threats to health, recent interpersonal problems and lifetime
      stressors. Recent LEs were more strongly associated with depression than anxiety
      whereas the associations for lifetime stressors were similar in strength. The
      strength of association between recent LEs and CMD increased steadily up to the
      45-54 years age group and then declined. In the 65-74 year age range, CMD was not
      significantly associated with any recent LE but instead was associated with the
      following lifetime stressors: bullying, sexual abuse, running away from home, and
      institutional care in childhood. CONCLUSIONS: Recent life events were most
      strongly associated with CMD in mid-rather than early or late adult life. In
      later life, stronger associations were found with lifetime stressors than recent
      events.

PMID- 17520163
TI  - Polymorphisms in ALOX12, but not ALOX15, are significantly associated with BMD in
      postmenopausal women.
AB  - The murine arachidonate 15-lipoxygenase gene (Alox15) has recently been
      identified as a negative regulator of peak bone mineral density (BMD). The human
      ALOX15 gene shares significant sequence homology with the murine Alox15 gene;
      however, the human arachidonate 12-lipoxygenase gene (ALOX12) is functionally
      more similar to the mouse gene. Multiple single-nucleotide polymorphisms (SNPs)
      in the human ALOX15 and ALOX12 genes have previously been reported to be
      significantly associated with BMD in humans. On the basis of these data, we
      carried out our own investigation of the human ALOX15 and ALOX12 genes and their
      relationship with hip and spine BMD parameters. The study population consisted of
      779 postmenopausal women with a mean (+/- standard deviation) age of 62.5 +/- 5.9
      years at BMD measurement and was recruited from a single large general practice
      in Chingford, northeast London. Three SNPs from ALOX15 and five from ALOX12 were
      analyzed. None of the SNPs that we analyzed in ALOX15 were significantly
      associated with any of the BMD parameters or fracture data. However, we found
      that three SNPs from ALOX12, all previously associated with spine BMD in women,
      were significantly associated with spine and various hip BMD parameters in our
      cohort (P = 0.029-0.049). In conclusion, we found no association between
      polymorphism in ALOX15 and BMD phenotypes but were able to replicate previous
      findings that genetic variation in ALOX12 seems to play a role in determining
      bone structure in Caucasian women.

PMID- 17520164
TI  - The difference between hazard and risk in the relation between bone density and
      fracture.
AB  - The relation between fracture risk and bone density is frequently defined in
      terms of a relative hazard derived from the Cox proportional hazards model. The
      relative hazard is a multiplicative factor representing the rise in hazard for
      each standard deviation fall in bone mineral density, which has a typical value
      of about 1.5. It is not generally appreciated that this hazard may only be
      equated with absolute risk when risk is very low; at higher risk and over long
      periods, it is inappropriate to apply a multiplicative factor to absolute risk
      because risk has a range of 0-1 and cannot exceed unity. Here, we show how
      "hazard" can be converted to risk and how misleading the current practice of
      equating relative hazards with relative risks can be.

PMID- 17520162
TI  - Social determinants of self-reported emotional and behavioral problems in Greek
      adolescents.
AB  - OBJECTIVE: This study aimed to assess the social factors associated with self
      reported emotional and behavioral problems among Greek adolescents. METHODS: At
      age 18, a population-based sample of 3373 Greek adolescents completed the Youth
      Self-Report (YSR) questionnaire. RESULTS: The results from the multivariate
      analysis indicated that both lack of intimate friendships and not having parental
      monitoring were independently associated with problem behavior among both male
      and female adolescents. Engagement in sexual activities was significantly
      associated with higher YSR scores among both genders. Absence of academic
      motivation was associated with higher YSR scores in girls only. CONCLUSIONS: Our
      results confirm that social factors, including negative family functions, lack of
      academic motivation and not having close friends, were associated with emotional
      and behavioral problems among adolescents and imply the need to develop a
      supportive social network for adolescents.

PMID- 17520165
TI  - Analysis of trabecular bone structure with multidetector spiral computed
      tomography in a simulated soft-tissue environment.
AB  - We investigated the influence of soft tissue (ST) on image quality by high
      resolution multidetector computed tomography (MDCT) scans and assessed the effect
      of surrounding ST on the quantification of trabecular bone structure. Eight bone
      cores obtained from human proximal femoral heads discarded during hip replacement
      surgery were scanned with micro-computed tomography (microCT) as well as with
      MDCT both without (w/o) and with (w) simulated surrounding ST, where a phantom
      imitated a human torso. Signal-to-noise ratio (SNR) and contrast-to-noise ratio
      (CNR) were measured in all scans. Apparent trabecular bone structure parameters
      were calculated and compared to similar parameters obtained in coregistered
      sections of the microCT scans. Residual errors were calculated as root-mean
      square (RMS) errors relative to the microCT measurements. Compared to microCT
      results, trabecular structure parameters were overestimated by MDCT both w and
      w/o ST. SNR and CNR were significantly higher in the scans w/o ST. Significant
      correlations between microCT and MDCT results were found for bone fraction (r =
      0.90 w/o ST, r = 0.84 w ST), trabecular number, and separation. RMS ranged from
      10% to 15% for MDCT w/o ST and from 10% to 17% for MDCT w ST. Only bone fraction
      showed significantly different RMS and correlations for scans w/o vs. w ST (P <
      0.05). This study showed that MDCT is able to visualize trabecular bone structure
      in an in vivo-like setting at skeletal sites within the torso such as the
      proximal femur. Even though ST scatter compromises image quality substantially,
      the major characteristics of the trabecular network can still be appreciated and
      quantified.

PMID- 17520166
TI  - Characterization of chromosomal inversion of the mouse hairy ears (Eh) mutation
      associated with cleft palate.
AB  - The hairy ears (Eh) mutation in the mouse originated from neutron irradiation
      experiments and is associated with chromosomal inversion on chromosome 15. Eh/+
      mice have small pinna and extra hairs on the pinna but the phenotypic features of
      Eh/Eh mice are unclear. In this study we found that Eh/Eh mice died shortly after
      birth and had a cleft palate caused by impaired growth of palate shelves. Because
      genes located on the breakpoints of inversion are likely to be responsible for
      the defects associated with chromosomal inversions, we determined the breakpoints
      of the Eh inversion. We used a new genetic method that uses recombinant
      chromosomes resulting from crossing over between two overlapping inversions to
      determine the breakpoints. Koa is a mouse mutation associated with inversion of
      chromosome 15, which partially overlaps with the Eh inversion. We made Eh +/+ Koa
      double heterozygotes and obtained the recombinant chromosomes possessing deletion
      and duplication of the regions flanked by the breakpoints of both inversions,
      which were generated by crossing over within the overlapped region of these
      inversions. By defining the deleted regions we identified the breakpoints of the
      Eh inversion. We then examined the expression of genes in the vicinities of the
      breakpoints and found ectopic expression of the Hoxc5 gene and a transcript with
      unknown function in the developing palate of Eh/Eh mice, which is likely to be
      responsible for the cleft palate.

PMID- 17520167
TI  - Diagnosis and conservative management of an arteriovenous fistula of the scalp
      following awake craniotomy for tumor resection.

PMID- 17520168
TI  - Short postal questionnaire and selective clinical examination combined with
      repeat mailing and telephone reminders as a method of follow-up in hernia
      surgery.
AB  - BACKGROUND: We assessed the usefulness of a short postal questionnaire and
      selective clinical examination combined with repeat mailing and telephone
      reminders for quality assessment in hernia surgery. METHODS: All patients (n =
      1153) who underwent tension-free hernioplasty through an open preperitoneal
      approach between 1999 and 2003 received a six-item questionnaire with a covering
      letter and a stamped addressed envelope. Nonresponders received two successive
      new questionnaires and a telephone call. RESULTS: A total of 841 (72.9%) patients
      returned questionnaires after three reminders (512 after the first mailing, 205
      after the second, and 124 after the third). Positive questionnaire answers were
      documented for 152 (18.1%) of repairs and negative answers for 689 (81.9%). Of
      the 152 patients who answered "yes" to either of the questions regarding
      recurrence and/or current pain, 91 declined clinical appointments, 24 could not
      be contacted by phone, and 37 underwent physical examination. Of the 312 patients
      who did not return the questionnaire, eight had died, 124 did not want to be
      visited, and 180 could not be located. The recurrence rate was 2.7% and the
      chronic pain rate 5.9%. CONCLUSIONS: Repeat mailing was a useful strategy to
      improve response to self-administered postal questionnaires on hernia surgery
      quality assessment. However, contacting the group that responded with positive
      questionnaire answers was a poorly effective way to encourage subjects to come
      for a physical examination.

PMID- 17520170
TI  - Laparoscopic repair of traumatic lumbar hernia.

PMID- 17520169
TI  - Definitive reconstruction of full-thickness abdominal wall defects initially
      treated with skin grafting of exposed intestines.
AB  - BACKGROUND: The reconstruction of wide, full-thickness abdominal wall defects of
      the midline presents a continuing challenge, and consensus concerning the
      appropriate surgical treatment is lacking. METHOD: In this retrospective review,
      we describe a simple method of reconstruction in full-thickness defects initially
      treated with skin grafting directly on to the surface of the intestines. Instead
      of removing the split-thickness grafts from the surface of the intestines, the
      abdominal wall was reconstructed by inverting the grafted area and advancing the
      rectus muscles towards the midline. RESULTS: Four patients with full-thickness
      transverse defects larger than 10 cm at the level of the waist and extending from
      the xiphoid to the suprapubic region were operated with this method. All healed
      uneventfully. In one case, microscopic examination of the inverted skin showed
      transformation to normal connective tissue. CONCLUSION: Reconstruction of
      abdominal wall defects previously treated with skin grafting directly on to the
      intestines can be safely done by reposition of the skin-grafted intestines into
      the abdominal cavity and realignment of the rectus muscles in the midline.

PMID- 17520171
TI  - Pericarditis: a rare complication of methotrexate therapy.
AB  - Serositis is a rare complication of methotrexate (MTX) administration. We report
      a 60-year-old man with rheumatoid arthritis who developed pericarditis after
      taking his weekly MTX dose, which recurred within hours after 2 subsequent weekly
      MTX doses. Pericarditis has not recurred after discontinuance of MTX over 3 years
      ago. We conclude that he had MTX-induced pericarditis, based on the close
      temporal relationship between MTX ingestion and manifestations of pericarditis on
      three distinct occasions because of the previous reports of MTX-induced
      pericarditis and because pericarditis has not recurred after MTX withdrawal.

PMID- 17520172
TI  - Effects of composite fissure sealants on IR laser fluorescence measurements.
AB  - The influence of composite fissure sealants on caries detection with IR laser
      fluorescence measurements should be assessed. Thirty-five extracted human teeth
      with 105 initial carious lesions were included. Six groups containing 15 lesions
      each were sealed with either a clear or a white version of three sealants. Group
      7 was sealed with an experimental nanofilled material. Occlusal surfaces were
      irradiated by a diode laser (<1 mW, 655 nm). Fluorescence was measured before and
      after acid etching, directly and 1 week after application of the sealants. Values
      significantly increased after etching (p < 0.05). Compared to initial
      measurements, values decreased after sealing with the white materials (p < 0.05).
      There was no difference between values before and after sealing with the clear
      and the experimental materials (p > 0.05). All values were reproducible. The
      study indicates that it might be possible to monitor caries activity under clear
      or nanofilled fissure sealants by means of laser fluorescence.

PMID- 17520173
TI  - Planar soap bubble clusters with a cavity.
AB  - We construct local energy-minimizing bubble clusters in the plane that are not
      simply-connected. Numerical evidence suggests that these minima are not isolated.

PMID- 17520174
TI  - Pomolic acid-induced apoptosis in cells from patients with chronic myeloid
      leukemia exhibiting different drug resistance profile.
AB  - Pomolic acid (PA) is a pentacyclic triterpene which has been previously described
      as active in inhibiting the growth of K562 cell line-originated from chronic
      myeloid leukemia (CML) in blast crisis-and its vincristine-resistant derivative
      K562-Lucena1. In this work, cells from CML patients were treated with PA and the
      apoptotic index was compared with the multidrug resistance (MDR) profile and
      clinical status of the patients. Our findings show that PA 12.5 microg/ml at 24 h
      (p = 0.000), at 48 h (p = 0.012) and at 72 h (p = 0.005) has a potent apoptotic
      index in CML cells as compared to mononuclear cells from healthy donors. PA was
      capable to induce apoptosis in cells from CML patients exhibiting functional MDR
      phenotype but not in P-glycoprotein expression. In addition, PA was effective in
      chronic as well as in blast phase of CML. Moreover, similar apoptotic index
      induced by PA was observed in low, intermediate and high-risk Sokal score as well
      as in samples from the group of patients with clinical resistance to interferon
      and/or imatinib and non-treated patients. These results suggest that PA may be an
      effective agent for the treatment of CML.

PMID- 17520176
TI  - Phase II trial of ixabepilone in patients with cisplatin-refractory germ cell
      tumors.
AB  - In a phase I study, ixabepilone, a novel non-taxane microtubule-stabilizing
      agent, demonstrated activity against both paclitaxel-sensitive and paclitaxel
      refractory solid tumors. We conducted a phase II trial of this agent in patients
      with advanced germ cell tumors (GCT) who were resistant to conventional
      therapies. Patients with cisplatin-refractory GCT were enrolled in this single
      institution, phase II trial. Ixabepilone was administered at a dose of 40 mg/m2
      intravenously over 3 hours every 21 days. Dose modifications were planned
      according to a nomogram for adverse events. Responses were assessed every 6 weeks
      using tumor markers and radiographic imaging according to the Response Evaluation
      Criteria in Solid Tumors (RECIST). Patients who progressed (>or=20% increase in
      tumor size or rising serum tumor markers) were taken off protocol. Twenty-nine
      cycles of treatment were administered to 12 patients. The most common Grade 3/4
      toxicities were leukopenia, lymphopenia, and neutropenia. One patient (8%)
      achieved a confirmed objective partial response but this patient had not received
      prior treatment with a taxane. Based on slow accrual and a lack of antitumor
      activity in patients previously treated with a taxane, the trial was closed after
      enrolling 12 patients. For patients who had previously received taxane therapy,
      ixabepilone was not efficacious in the treatment of cisplatin-refractory GCT.

PMID- 17520175
TI  - Different cell cycle modulation following treatment of human ovarian carcinoma
      cells with a new platinum(IV) complex vs cisplatin.
AB  - Platinum (IV) derivative with adamantylamine-LA-12-represents a new generation of
      highly efficient anti-cancer drug derived from cisplatin and is currently in the
      final stage of phase I clinical trials. Understanding the specific mechanisms of
      its effects on cell cycle is necessary for defining the mode of action of LA-12.
      In this study, we characterized the ability of LA-12 to induce cell cycle
      perturbations in ovarian cancer cell line A2780 as compared to equitoxic
      cisplatin treatment. LA-12 induced a permanent accumulation of A2780 cells in S
      phase while cisplatin caused G2/M arrest at 24-h time point, where we also
      detected an increased expression of Gadd45alpha protein. Although both
      derivatives induced a rapid increase of p53 expression, this was not associated
      with a down-regulation of Mdm2 protein. Increased expression of p21(Cip1/WAF1)
      protein and its association with cyclins A and B1 suggested that this cyclin
      dependent kinase inhibitor might contribute significantly to the observed
      perturbations of cell cycle. The results of this study provide insight into the
      mechanism of action of platinum-based derivative with adamantylamine on cell
      cycle in ovarian cancer cells. The differences between effects of LA-12 and
      cisplatin suggest that more attention should be paid to elucidation of modes of
      action of novel platinum(IV) complexes at cellular level.

PMID- 17520177
TI  - Cell growth restoration and high level protein expression by the promoter of
      hexose transporter, HXT7, from Saccharomyces cerevisiae.
AB  - The promoters of high-affinity hexose transporter, HXT6 and HXT7, are sufficient
      for complementary expression of invertase to restore the growth of Saccharomyces
      cerevisiae in raffinose medium. The HXT7 promoter produced higher invertase
      activity at 139- and 30-fold of the basal activity in strains GN 3C.2 and W303-1,
      respectively. In addition, the HXT7 promoter expressed 3- to 9-fold more of
      enhanced green fluorescent protein than that of the constitutive ADH1 in three
      different S. cerevisiae strains, even during short-term incubation in glucose
      medium. Therefore, HXT7 promoter could be used for heterologous protein
      expression in S. cerevisiae.

PMID- 17520178
TI  - Heterologous expression and site-directed mutagenesis of endoglucanase CelA from
      Clostridium thermocellum.
AB  - The endoglucanase CelA from Clostridium thermocellum was strongly expressed in
      Bacillus subtilis. The enzyme was purified by Ni(2+)-affinity chromatography.
      Site-directed substitution of D278 with an asparagine or an alanine residue
      surprisingly did not decrease the apparent k(cat) value. Further substitutions of
      two other potentially critical residues, Y215 and D152, resulted in a 2-fold
      decrease in apparent k(cat) value for Y215P and complete loss of activity for
      D152N.

PMID- 17520179
TI  - The lack of expression of the peripheral benzodiazepine receptor characterises
      microglial response in anaplastic astrocytomas.
AB  - The peripheral benzodiazepine receptor (PBR) is a 18 kDa molecule mainly involved
      in cholesterol transport through the mitochondrial membrane. In microglia, PBR is
      expressed from the earliest stages of activation and appears to exert a pro
      inflammatory function. This molecule is commonly up-regulated in inflammatory,
      degenerative, infective and ischaemic lesions of the central nervous system but
      it has never been reported in glioma-infiltrating microglia. We examined two
      anaplastic astrocytomas showing minimal contrast-enhancement and therefore little
      damage of the blood brain barrier to minimise the presence of blood borne
      macrophages within tumour tissue. The two lesions were studied in vivo using
      positron emission tomography (PET) with the specific PBR ligand [(11)C](R)
      PK11195 and the corresponding tumour tissue was investigated with an anti-PBR
      antibody. Glioma-infiltrating microglia were characterised for molecules involved
      in antigen presentation and cytotoxic activity. As comparison, PBR was
      investigated in three brains with multiple sclerosis (MS) and three with
      Parkinson's disease (PD). The expression profile of four anaplastic astrocytomas
      was also exploited and results were compared to the profile of eleven samples of
      normal temporal lobe and nine cases of PD. PET studies showed that [(11)C](R)
      PK11195 binding was markedly lower in tumours than in the contralateral grey
      matter. Pathological investigation revealed that glioma-infiltrating microglia
      failed to express PBR and cytotoxic molecules although some cells still expressed
      antigen presenting molecules. PBR and cytotoxic molecules were highly represented
      in MS and PD. Evaluation of microarray datasets confirmed these differences. Our
      results demonstrated PBR suppression in glioma-infiltrating microglia and
      suggested that PBR may have a relevant role in modulating the anti-tumour
      inflammatory response in astrocytic tumours.

PMID- 17520180
TI  - Ability of different polymers to inhibit the crystallization of amorphous
      felodipine in the presence of moisture.
AB  - PURPOSE: To investigate the ability of various polymers to inhibit the
      crystallization of amorphous felodipine from amorphous molecular dispersions in
      the presence of absorbed moisture. METHODS: Spin coated films of felodipine with
      poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose acetate succinate
      (HPMCAS) and hydroxypropylmethylcellulose (HPMC) were exposed to different
      storage relative humidities and nucleation rates were measured using polarized
      light microscopy. Solid dispersions were further characterized using differential
      scanning calorimetry, infrared spectroscopy and gravimetric measurement of water
      vapor sorption. RESULTS: It was found that the polymer additive reduced
      nucleation rates whereas absorbed water enhanced the nucleation rate as
      anticipated. When both polymer and water were present, nucleation rates were
      reduced relative to those of the pure amorphous drug stored at the same relative
      humidity, despite the fact that the polymer containing systems absorbed more
      water. Differences between the stabilizing abilities of the various polymers were
      observed and these were explained by the variations in the moisture contents of
      the solid dispersions caused by the different hygroscopicities of the component
      polymers. No correlations could be drawn between nucleation rates and the glass
      transition temperature (Tg) of the system. PVP containing solid dispersions
      appeared to undergo molecular level changes on exposure to moisture which may be
      indicative of phase separation. CONCLUSIONS: In conclusion, it was found that for
      a given storage relative humidity, although the addition of a polymer increases
      the moisture content of the system relative to that of the pure amorphous drug,
      the crystallization tendency was still reduced.

PMID- 17520181
TI  - Pharmacokinetics and safety of a fully human hepatocyte growth factor antibody,
      AMG 102, in cynomolgus monkeys.
AB  - PURPOSE: AMG 102, a fully human monoclonal antibody that binds to hepatocyte
      growth factor (HGF), is a potential cancer therapeutic agent because of its
      ability to disrupt HGF/c-Met signaling pathways which have been implicated in
      most tumor types. To support a phase 1 study, the pharmacokinetic and safety
      profile of AMG 102 was assessed in cynomolgus monkeys. MATERIALS AND METHODS:
      Serum concentration-time data from single- (i.v. and s.c.) and repeated-dose
      (i.v.) studies of up to 13 weeks were used for pharmacokinetic analysis. Safety
      was assessed in a single-dose safety pharmacology study with i.v. doses of 0
      (vehicle), 25, 100, or 300 mg/kg and a 4-week toxicity study with once weekly
      i.v. doses of 0 (vehicle), 5, 25, or 100 mg/kg. RESULTS: AMG 102 exhibited linear
      pharmacokinetics over a 600-fold dose range (0.5 to 300 mg/kg) with a mean
      terminal half-life of 5.6 days after i.v. dosing. Clearance and volume of
      distribution at steady state were 1.22 ml/h and 198.3 ml, respectively. Estimated
      bioavailability was 72% for s.c. administration. Antibody response to AMG 102 was
      observed in a small percentage of monkeys. No treatment-related cardiovascular,
      respiratory, or CNS changes were observed. Administration of AMG 102 for 4 weeks
      was well tolerated at doses up to 100 mg/kg. Potential treatment-related effects
      were limited to minimal/moderate gastric mucosa hemorrhage in the mid- and high
      dose groups. CONCLUSIONS: The nonclinical pharmacokinetic and safety profile of
      AMG 102 effectively supports clinical investigation.

PMID- 17520182
TI  - Current status and new developments in ion therapy.
AB  - BACKGROUND: Worldwide, encouraging clinical results of ion radiotherapy led to
      planning and construction of several new treatment facilities. MATERIAL AND
      METHODS: The main technical and biological aspects of ion therapy are reviewed.
      The current status and future developments are discussed. RESULTS: The use of
      ions in radiotherapy results in highly conformal dose distributions. The degree
      of conformality is higher for active than for passive beam delivery techniques.
      Applying ion therapy, uncertainties in the range and the biologically effective
      dose have to be considered. For heavy ions, the clinical value of the increased
      biological efficiency has to be investigated. CONCLUSION: Although the principal
      methods for clinical application of ion therapy are available, the development
      must be continued to explore its full potential.

PMID- 17520183
TI  - Concurrent chemoradiotherapy for advanced pancreatic cancer: 1,000 mg/m2
      gemcitabine can be administered using limited-field radiotherapy.
AB  - PURPOSE: To examine the feasibility of concurrent use of full-dose gemcitabine
      (GEM) and radiotherapy for advanced pancreatic cancer. PATIENT AND METHODS: 22
      patients with advanced pancreatic cancer were subjected to concurrent
      chemoradiotherapy (GEM 1,000 mg/m(2) weekly, three times during 4 weeks). They
      received limited-field irradiation by three-dimensional radiotherapy planning.
      RESULTS: Of the 22 patients, 16 (72%) completed the treatment (50 Gy irradiation
      and at least three times concurrent administration of 1 g/m(2) GEM). One patient
      with unresectable tail cancer showed peritonitis carcinomatosa and both
      chemotherapy and radiotherapy had to be stopped. Dose reduction or omission of
      GEM was necessary in another four patients. In addition, radiotherapy was
      discontinued in one patient for fatigue. Grade 3 hematologic toxicity was
      detected in eight patients (36%), and grade 3 nonhematologic toxicity (anorexia)
      in one patient (5%). In total, the response rate amounted to 32% (seven partial
      responses), and the median survival time (MST) was 16 months. Among the twelve
      patients who received preoperative chemoradiotherapy, nine underwent surgery and
      showed a survival rate of 78% at 1 year. Another 13 patients without surgery
      showed 14 months of MST. No regional lymph node failure has appeared so far.
      CONCLUSION: Limited-field radiotherapy enables the safe concurrent administration
      of 1,000 mg/m(2) GEM.

PMID- 17520184
TI  - Precision of image-guided radiotherapy (IGRT) in six degrees of freedom and
      limitations in clinical practice.
AB  - PURPOSE: To evaluate the precision of image-guided radiotherapy (IGRT) using cone
      beam computed tomography (CB-CT) for volume imaging and a robotic couch for
      correcting setup errors in six degrees of freedom. PATIENTS AND METHODS: 47
      consecutive patients with 372 fractions were classified according to whether a
      patient fixation device was used (pat(fix): n = 28) or not (pat(non-fix): n =
      19). Prior to treatment a CB-CT was acquired and translational and rotational
      setup errors were corrected online without an action level using a robotic couch
      (HexaPOD). A second CB-CT was acquired after the correction process and after
      treatment in 134 and 238 fractions, respectively. RESULTS: In 17 fractions (4.6%)
      rotational errors > 3 degrees exceeded the motion range of the HexaPOD. Errors
      (3D vector) after the correction process were significantly smaller for pat(fix)
      compared to pat(non-fix) (p < 0.001): 0.9 mm +/- 0.5 mm and 1.6 mm +/- 0.8 mm,
      respectively. For pat(non-fix) the correction of rotational errors resulted in
      displacements of the patients on the angled couch of 0.6 mm/1 degree.
      Intrafractional motion further decreased precision in pat(non-fix) but not in
      pat(fix). CONCLUSION: Very high precision in cranial and extracranial treatment
      of immobilized patients was demonstrated. Without application of adequate
      immobilization the correction of rotational errors and intrafractional patient
      motion significantly decreased the accuracy of the online correction protocol.

PMID- 17520185
TI  - Patterns of care in the radiotherapy of prostate cancer in Northern Bavaria 1998
      2000.
AB  - PURPOSE: A patterns-of-care study of radiotherapy (RT) in prostate cancer was
      performed in Northern Bavaria, Germany, to characterize patient selection,
      treatment strategies and outcome for the time period 1998-2000. MATERIAL AND
      METHODS: Patients who received curative-intent radical or postoperative RT were
      identified from the databases of six centers (one university, five
      teaching/regional hospitals). Two centers treated < 20 patients and were excluded
      from further analysis. At the remaining four centers, 148 patients receiving
      radical RT and 134 undergoing postoperative RT were analyzed for pretreatment and
      RT characteristics and actuarial biochemical control (BC; ASTRO definition).
      RESULTS: All patients were treated with three-dimensional conformal external-beam
      techniques. In radical RT patients, cT- and cN-stages as well as the frequency of
      (neo)adjuvant hormonal therapy (53-91%) and RT to pelvic nodes (2-97%) and the
      mean total RT dose (64.8-71.0 Gy) varied significantly between centers. In
      postoperative RT, centers differed significantly in R-status, initial prostate
      specific antigen (PSA) and nodal RT frequency (2-89%), whereas total RT doses
      were similar (62.3-64.8 Gy). After radical RT, 5-year BC was 68.6% and differed
      significantly between centers on univariate analysis. In a multivariate model,
      only total RT dose showed a trend toward an effect on BC. In postoperative RT
      patients, overall 5-year BC was 82.1%, and age and initial PSA were associated
      with BC on multivariate analysis. CONCLUSION: From 1998 to 2000, radical RT for
      prostate cancer at the Northern Bavarian centers now studied was performed with
      three-dimensional conformal technique to conservative total doses and selection
      criteria for postoperative RT were highly variable.

PMID- 17520186
TI  - Single-institution results of primary external-beam radiation for the treatment
      of t1-t3 prostate cancer.
AB  - PURPOSE: To evaluate survival and toxicity rates after primary external-beam
      radiation for the treatment of prostate cancer. PATIENTS AND METHODS: Data of 306
      patients treated with conformal external beam radiation between 1996 and 2001
      were collected. These were evaluated in terms of overall, cause-specific and
      disease-free survival as well as toxicity. Furthermore, an investigation of
      possible risk factors was performed. RESULTS: Toxicity rates compared favorably
      with other series with 5.2% RTOG 1-2 and no RTOG > 2 long-term side effects.
      Actuarial 5-year overall survival rates with and without biochemical failure were
      77% versus 78%, cancer-specific survival was 85.41% versus 100%, and disease-free
      survival was 71.54%, respectively. Potential risk factors for cancer-related
      death were biochemical failure, initial serum prostate-specific antigen (PSA) and
      Gleason score. CONCLUSION: Toxicity rates were found to be surprisingly low
      compared to other series, which is likely due to low daily dose and consistent MR
      based treatment planning. In terms of survival, no significant differences to
      other trials could be observed. Initial PSA and Gleason score were significant
      predictors for treatment outcome in terms of survival.

PMID- 17520187
TI  - Linearity of the dose monitor system at low monitor units.
AB  - BACKGROUND AND PURPOSE: The accuracy of the dose monitor system of a medical
      electron accelerator is of crucial importance for the precise delivery of the
      prescribed dose. Special attention is given to the case of low monitor units
      (MU). The long-term stability of the dose monitor system is analyzed. MATERIAL
      AND METHODS: Photon and electron fields with monitor units between 1 and 500 MU
      were measured with field sizes of 10 x 10 cm(2) and 20 x 20 cm(2) at source-skin
      distances (SSDs) of 100 cm and 95 cm, respectively. The relative dose per MU [see
      text] was determined for an Elekta linear accelerator. RESULTS: The relative dose
      per MU was measured to be constant within about 1% down to fields with only 2 MU.
      The deviation remained below 2% down to 1 MU which is the minimum setting of the
      accelerator. The long-term stability is better than 0.2% per month. CONCLUSION:
      No therapeutically relevant deviation of the prescribed dose could be detected
      for the Elekta linear accelerator. This is a prerequisite for the implementation
      of intensity-modulated radiotherapy (IMRT) techniques.

PMID- 17520188
TI  - Scattered dose to gonads and associated risks from radiotherapy for common
      pediatric malignancies : a phantom study.
AB  - PURPOSE: To measure the scattered dose to ovaries and testes from radiotherapy
      for common pediatric malignancies and to assess the relevant risks for radiation
      induced gonadal damage and hereditary disorders in future generations. MATERIAL
      AND METHODS: Radiotherapy for central nervous system tumors, acute leukemia,
      neuroblastoma, Hodgkin's disease, Wilms' tumor, and sarcoma was simulated on
      three humanoid phantoms representing patients of 5, 10, and 15 years of age.
      Ovarian and testicular dose measurements were performed using thermoluminescent
      dosimeters on a linear accelerator with multileaf collimator (MLC) producing 6-MV
      X-rays. The effect of lead block introduction into the primary beam on the
      gonadal dose was evaluated. Gonadal dose from radiotherapy for abdominal tumors
      was measured using an 18-MV photon beam. RESULTS: For a tumor dose range of 12-55
      Gy, the scattered dose to ovaries was 0.5-62.4 cGy depending upon the patient's
      age (corresponding phantom) and treatment site. The corresponding dose to testes
      was 0.4-145.0 cGy. The use of blocks for field shaping can increase the gonadal
      dose up to a factor of 2.0 compared to that measured using MLC. Abdominal
      irradiation with 18-MV instead of 6-MV X-rays reduced the gonadal dose by more
      than 1.3 times. For female and male patients, the risk for induction of
      hereditary disorders was less than 81 x 10(-4) and 188 x 10(-4), respectively.
      CONCLUSION: The present dosimetric data suggest that pediatric radiotherapy is
      not associated with a risk for permanent damage to gonads excluded from the
      treatment volume. The risk for development of hereditary disorders in offspring
      conceived after exposure is low.

PMID- 17520189
TI  - [Intracerebrally localized sarcoma NOS--an interdisciplinary challenge].
AB  - BACKGROUND: In the literature, surveys of malignant intracerebral nerve sheath
      tumors are very rare (Table 1). Therapeutic guidelines do not exist. CASE REPORT:
      A 28-year-old female patient presented with a tumor in the postcentral region of
      the left parietal lobe (Figures 1 and 2). The specimen could not be categorized
      into a common tumor entity and was classified as sarcoma NOS. Shortly after
      surgery, a recurrence occurred (Figures 3 to 5) followed by a further excision.
      Due to the rapid tumor growth irradiation with CT-aided treatment planning
      (Figure 6) has been started immediately afterwards. A dose of 5,400 cGy in 22
      fractions was administered. RESULT: 2 weeks after treatment, the patient
      presented with a noticeable tumor regression (magnetic resonance imaging; Figures
      7 to 9). She developed pulmonary metastases. A partial remission could be
      achieved by systemic chemotherapy. Unfortunately, the patient died because of an
      exacerbation of a hepatic encephalopathy. CONCLUSION: In cases of intracerebrally
      localized sarcomas NOS, the earliest possible start of radiotherapy after surgery
      seems useful because of the noticed radiosensitivity of these tumors. In regard
      of the local control, this tumor entity shows a documented excellent response to
      radiotherapy. Expectedly, distant metastases cannot be influenced.
      Interdisciplinary cooperation is mandatory to enhance the diagnostic process, the
      treatment decisions, and the results.

PMID- 17520190
TI  - Some clinical results on selenium in radiation oncology: letter by O. Micke, R.
      Mucke, F. Bruns, K. Kisters, J. Buntzel on W. Dorr: Effects of selenium on
      radiation responses of tumor cells and tissue in: Strahlenther Onkol 2006;182:693
      5 (No. 12) (DOI 10.1007/s00066-006-1595-8).

PMID- 17520191
TI  - Real-time monitoring full length bid interacting with Bax during TNF-alpha
      induced apoptosis.
AB  - Bid, a member of the pro-apoptotic Bcl-2 protein family, is activated through
      caspase-8-mediated cleavage into a truncated form (p15 tBid) during TNF
      alpha(tumor necrosis factor alpha)-induced apoptosis. Activated tBid can induce
      Bax oligomerization and translocation to mitochondria, triggering the release of
      cytochrome c, caspase-3 activation and cell apoptosis. However, it is debatable
      that whether Bid and tBid can interact directly with Bax in living cells. In this
      study, we used confocal fluorescence microscope, combined with both FRET
      (fluorescence resonance energy transfer) and acceptor photobleaching techniques,
      to study the dynamic interaction between Bid and Bax during TNF-alpha-induced
      apoptosis in single living cell. In ASTC-a-1 cells, full length Bid induced Bax
      translocation to mitochondria by directly interacting with Bax transiently in
      response to TNF-alpha treatment before cell shrinkage. Next, we demonstrated
      that, in both ASTC-a-1 and HeLa cells, Bid was not cleaved before cell shrinkage
      even under the condition that caspase-8 had been activated, but in MCF-7 cells
      Bid was cleaved. In addition, in ASTC-a-1 cells, caspase-3 activation was a
      biphasic process and Bid was cleaved after the second activation of caspase-3. In
      summary, these findings indicate that, FL-Bid (full length-Bid) directly
      regulated the activation of Bax during TNF-alpha-induced apoptosis in ASTC-a-1
      cells and that the cleavage of Bid occurred in advanced apoptosis.

PMID- 17520192
TI  - Influence of pan-caspase inhibitors on coxsackievirus B3-infected CD19+ B
      lymphocytes.
AB  - Coxsackievirus B3 (CVB3), together with other enteroviruses of the picornavirus
      family, is associated with a wide variety of acute and chronic forms of human
      diseases. Using the murine model of CVB3-caused myocarditis, this pathogen can be
      detected not only in solid organs but also in different types of immune cells,
      preferentially in B lymphocytes. Therefore, these cells could represent a non
      cardiac virus reservoir and may play an important role with regard to viral
      dissemination in the infected host. In addition, the infection of specific immune
      cells might modulate the severity of tissue injury and the pattern of virus
      caused pathology in susceptible or resistant individuals. In the present study it
      could be demonstrated that CVB3 was capable to infect productively a certain
      percentage of murine CD19(+) B cells. In vivo studies revealed that CVB3 invaded
      murine CD19(+) B cells during an acute infection. Three days p. i. approximately
      0.5-1.0% of these cells were productively infected. This proportion could be
      decreased up to 45%, if 3 days p. i. mice were intravenously treated with the pan
      caspase inhibitors Z-VAD-FMK or Q-VD-OPH. These data were compared with results
      obtained from CVB3-infected human Raji cells.

PMID- 17520193
TI  - Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null
      HCT116 colon carcinoma cells.
AB  - Non-ionizing radiation produced by nanosecond pulsed electric fields (nsPEFs) is
      an alternative to ionizing radiation for cancer treatment. NsPEFs are high power,
      low energy (non-thermal) pulses that, unlike plasma membrane electroporation,
      modulate intracellular structures and functions. To determine functions for p53
      in nsPEF-induced apoptosis, HCT116p53(+/+) and HCT116p53(-/-) colon carcinoma
      cells were exposed to multiple pulses of 60 kV/cm with either 60 ns or 300 ns
      durations and analyzed for apoptotic markers. Several apoptosis markers were
      observed including cell shrinkage and increased percentages of cells positive for
      cytochrome c, active caspases, fragmented DNA, and Bax, but not Bcl-2. Unlike
      nsPEF-induced apoptosis in Jurkat cells (Beebe et al. 2003a) active caspases were
      observed before increases in cytochrome c, which occurred in the presence and
      absence of Bax. Cell shrinkage occurred only in cells with increased levels of
      Bax or cytochrome c. NsPEFs induced apoptosis equally in HCT116p53(+/+) and
      HCT116p53(-/-) cells. These results demonstrate that non-ionizing radiation
      produced by nsPEFs can act as a non-ligand agonist with therapeutic potential to
      induce apoptosis utilizing mitochondrial-independent mechanisms in HCT116 cells
      that lead to caspase activation and cell death in the presence or absence of p-53
      and Bax.

PMID- 17520194
TI  - Doxorubicin enhances TRAIL-induced cell death via ceramide-enriched membrane
      platforms.
AB  - Previous studies indicated that signalling via CD95 and DR5 is greatly enhanced
      by the formation of ceramide-enriched membrane platforms. Here, we employed this
      concept to convert doses of subtherapeutic TRAIL that were unable to release
      ceramide and kill leukemic B-cells or ex vivo T lymphocytes, into a very
      effective apoptotic stimulus. Ceramide production was induced by application of
      sub-toxic doses of doxorubicin that resulted in an activation of the acid
      sphingomyelinase (ASM), release of ceramide and formation of ceramide-enriched
      membrane platforms. The latter served DR5 to cluster after application of very
      low doses of TRAIL in combination with doxorubicin. Genetic deficiency of the ASM
      abrogated doxorubicin-induced ceramide release, as well as clustering of DR5 and
      apoptosis induced by the combined treatment of doxorubicin and TRAIL. These data
      show that local release of ceramide potentiates very low, otherwise inactive
      doses of TRAIL that may represent a novel therapeutic concept to treat tumors.

PMID- 17520195
TI  - Current understanding of precursors to pancreatic cancer.
AB  - Precursors to pancreatic cancer have been investigated for a century. Previous
      studies have revealed three distinct precursors, i.e. mucinous cystic neoplasm
      (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic
      intraepithelial neoplasia (PanIN), harboring identical or similar genetic
      alterations as does invasive pancreatic carcinoma. The current understanding of
      precursors to pancreatic cancer can be illustrated by progressive pathways from
      noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of
      ovarian-type stroma and epithelial lining with varying grades of atypia, and are
      occasionally associated with invasive adenocarcinoma. The epithelium of
      noninvasive IPMNs shows a variety of different directions of differentiation,
      including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs
      can also harbor varying grades of architectural and cytologic atypia. IPMNs
      confined to branch ducts are mostly the gastric type, and IPMNs involving the
      main ducts are often intestinal type, while PB and oncocytic types are rare.
      Small (<1 cm) IPMNs of the gastric type are not always morphologically
      distinguishable from low-grade PanINs. Mucin expression profiles suggest
      intestinal-type IPMNs progress to mucinous noncystic (colloid) carcinoma, while
      PB-type IPMNs progress toward ductal adenocarcinoma. It is a well-described
      paradigm that PanIN lesions progress toward ductal adenocarcinoma through step
      wise genetic alterations. The activation of Hedgehog and Notch signaling pathways
      in PanIN lesions as well as in pancreatic adenocarcinoma suggest that
      developmental pathways may be disregulated during carcinogenesis of the pancreas.
      Further study is needed to elucidate the pathways from precursors toward invasive
      carcinoma of the pancreas.

PMID- 17520197
TI  - Molecular genetics of intraductal papillary-mucinous neoplasms of the pancreas.
AB  - Intraductal papillary-mucinous neoplasms of the pancreas show characteristic
      clinicopathological and molecular pathobiological features which are distinct
      from those of conventional ductal adenocarcinomas. Alterations of KRAS, AKT/PKB,
      CDKN2A, TP53, SMAD4, STK11/LKB1, and DUSP6, and other molecular alterations,
      including global expression studies as well as their clinical implications, are
      discussed.

PMID- 17520198
TI  - Mucinous cystic neoplasms of the pancreas: pathology and molecular genetics.
AB  - Mucinous cystic neoplasm (MCN) of the pancreas is a distinct clinicopathological
      entity characterized by mucin-producing epithelial and cyst-forming neoplasm with
      "ovarian-type" stroma beneath the epithelial component. It is clearly
      distinguished from ductal adenocarcinoma and intraductal papillary mucinous
      neoplasm (IPMN). However, MCN can progress to infiltrating carcinoma, and
      frequently shows a similar histological pattern to ductal adenocarcinoma. Several
      genetic alterations such as K-ras oncogene mutation, and epigenetic alterations
      such as hypermethylation of p16 in the invasive component of MCN are also common
      with ductal adenocarcinoma. Furthermore, recent technologies, including a laser
      assisted microdissection system for histological slides and global gene
      expression profilings using DNA microarrays, made possible to identify more
      information about molecular abnormalities of MCNs. It is important to diagnose
      the lesions before they progress to an invasive carcinoma. MCN is one of the
      precursors of invasive pancreatic carcinoma.

PMID- 17520196
TI  - Molecular genetics of pancreatic intraepithelial neoplasia.
AB  - BACKGROUND: Recent evidence suggests that noninvasive precursor lesions,
      classified as pancreatic intraepithelial neoplasia (PanIN), can progress to
      invasive pancreatic cancer. This review will discuss the major genetic
      alterations in PanIN lesions. METHODS: A comprehensive review of the literature
      was performed in order to find studies on the molecular profile of human PanIN
      lesions. In addition, recent publications on genetically engineered mouse models
      of preinvasive neoplasia and pancreatic cancers were reviewed. RESULTS: PanINs
      demonstrate abnormalities at the genomic (DNA), transcriptomic (RNA), and
      proteomic levels, and there is a progressive accumulation of molecular
      alterations that accompany the histological progression from low-grade PanIN-1A
      to high-grade PanIN-3 lesions. Molecular changes in PanINs can be classified as
      "early" (KRAS2 mutations, telomere shortening, p21(WAF1/CIP1) up-regulation,
      etc.), "intermediate" (cyclin D1 up-regulation, expression of proliferation
      antigens, etc.), or "late" (BRCA2 and TP53 mutations, DPC4/SMAD4/MADH4
      inactivation, etc.). All the genetic changes observed in PanINs are also found in
      invasive ductal adenocarcinomas, where they usually occur at a higher frequency.
      Genetically engineered mice expressing mutant Kras in the pancreas, with or
      without additional genetic alterations, provide a unique in vivo platform to
      study the pancreatic cancer progression model. CONCLUSIONS: Molecular studies
      have been instrumental in establishing that PanIN lesions are the noninvasive
      precursors for invasive ductal adenocarcinomas. The availability of molecular
      date provides the basis for designing rational early detection strategies and
      therapeutic intervention trials before pancreatic neoplasms invade, with the
      intention of alleviating the dismal prognosis associated with this disease.

PMID- 17520199
TI  - Mucin expression profile in pancreatic cancer and the precursor lesions.
AB  - In this review article, we demonstrate the mucin expression profile in normal
      tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary
      mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic
      intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the
      pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated
      MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression
      of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low
      expression of all the glycoforms of MUC1. IPMNs clear cell type showed low
      expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and
      fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs
      dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in
      IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher
      in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study
      demonstrated that high expression of MUC4 in IDCs is correlated with a poor
      outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early
      event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they
      will show a specific mucin expression profile according to the literature review.

PMID- 17520200
TI  - Clinical importance of precursor lesions in the pancreas.
AB  - Three distinct noninvasive precursor lesions to invasive ductal adenocarcinoma of
      the pancreas have been described. These include the mucinous cystic neoplasm,
      intraductal papillary mucinous neoplasm, and pancreatic intraepithelial
      neoplasia. The early detection and treatment of these lesions can interrupt the
      progression of a curable noninvasive precursor to an almost uniformly deadly
      invasive cancer.

PMID- 17520201
TI  - Pylorus-preserving total pancreatectomy for an intraductal papillary-mucinous
      neoplasm of the pancreas.
AB  - BACKGROUND/PURPOSE: Total pancreatectomy (TP) is rarely performed to treat
      invasive ductal carcinoma of the pancreas, due to the associated markedly
      impaired quality of life and poor prognosis after the resection. Intraductal
      papillary-mucinous neoplasm (IPMN) of the pancreas is characterized by extensive
      intraductal spread and a favorable outcome even when presenting at an invasive
      stage. We herein reappraise the role of pylorus-preserving total pancreatectomy
      (PPTP) as a viable alternative pancreatic resection modality for borderline and
      malignant IPMN. METHODS: A total of five patients with IPMN underwent PPTP and
      their clinical follow-up data were reviewed. RESULTS: TP was performed due to
      recurrent IPMN in the remnant pancreas after distal pancreatectomy in three
      patients and due to massive involvement of the entire pancreas in the others. All
      patients were treated by the pylorus-preserving method, while the spleen was also
      preserved in one patient. The surgical margins were negative and no metastasis to
      the resected lymph nodes was evident, based on histological examinations. One
      patient underwent a re-operation due to postoperative intraabdominal bleeding,
      while another patient required tubedrainage for left pleural effusion. Three of
      the four patients who underwent PPTP with a splenectomy experienced postoperative
      gastric ulcer, which were controlled by medication. One patient died due to
      suicide 16 months after the PPTP. All the others were doing well without
      recurrence at periods of 62 to 127 months after the PPTP. CONCLUSIONS: PPTP is
      therefore considered to be indicated as an effective treatment for borderline or
      malignant IPMN with extensive involvement, when the patient's condition permits,
      in order to achieve complete resection of the IPMN.

PMID- 17520202
TI  - Use of an opened umbilical vein patch for the reconstruction of the injured
      biliary tract.
AB  - BACKGROUND/PURPOSE: When iatrogenic biliary tract injury occurs, there is the
      risk of complications such as bile leak and biliary stricture, and
      hepaticojejunostomy is the conventional procedure used for injury repair.
      However, this procedure can be complicated by retrograde biliary tract infection
      and the procedure can destroy the normal anatomical structure. METHODS: We report
      here a method of end-to-end biliary tract reconstruction that uses an opened
      umbilical vein (OUV) patch and two stents to reduce bile leakage and biliary
      stricture formation following injury to the common bile duct or right main bile
      duct. The postoperative courses of four patients are reviewed. RESULTS: In two of
      the patients, there was a small amount of postoperative bile drainage (for 3 days
      in the first patient and 2 days in the second patient). Of the two stents, the
      first stent was removed 1 month postoperatively, and the second stent at 2 to 3
      months postoperatively. Three patients have returned to normal activity without
      symptoms after 44, 62, and 93 months, respectively. One patient died of a liver
      tumor recurrence in the fifth postoperative month, without a biliary problem.
      CONCLUSIONS: An OUV patch for end-to-end biliary reconstruction reduced the
      volume and duration of bile leakage. Further research is needed to accurately
      evaluate the stenting period so as to reduce its duration.

PMID- 17520203
TI  - Evaluation of tumor growth in vivo in a rat model of liver metastasis, using a
      newly devised index obtained by positron emission tomography with [18F] FDG.
AB  - BACKGROUND/PURPOSE: [(18)F] fluorodeoxyglucose-positron emission tomography (FDG
      PET) is regarded as a unique imaging modality, because the images reflect tumor
      activity. This characteristic of PET encouraged us to use it to develop a novel
      method of quantitatively measuring liver metastasis viability. METHODS: F344 rats
      were injected with rat colon adenocarcinoma cells (RCN-9 cell line) via the
      portal vein, and some of them were treated with 5-fluorouracil (5-FU). Tumor
      growth and tumor activity were measured by PET. We used a tumor viability index
      (TVI) to evaluate changes in tumor activity and to quantitatively evaluate tumor
      proliferation activity, instead of using the standardized uptake value (SUV) of
      the tumor tissue. The TVI was compared with the number of tumor nodules and the
      proliferating cell nuclear antigen (PCNA) index 28 days after RCN-9 cell
      inoculation. RESULTS: [(18)F] FDG uptake by the liver tumors was measured by PET,
      and the TVI was found to increase as the tumor nodules increased in number and
      size. The TVI values in the experimental model represented the viability of
      tumors suppressed by chemotherapy, and the values were significantly correlated
      with the number of nodules and the PCNA index. CONCLUSIONS: The TVI was concluded
      to be superior to the SUV, the commonly used indicator, for evaluating tumor
      growth, especially that of multiple, small tumors.

PMID- 17520204
TI  - Invasive ductal adenocarcinoma of the pancreas may originate from the larger
      pancreatic duct: a study of 13 tumors less than 2 cm in diameter.
AB  - BACKGROUND/PURPOSE: We aimed to elucidate the origin/primary site of invasive
      ductal adenocarcinoma of the pancreas, based on the distribution of intraductal
      carcinoma components. These components were identified by a mural elastic fiber
      cuff. METHODS: Thirteen specimens from patients with invasive ductal
      adenocarcinoma (microscopically, less than 2 cm in diameter) of the pancreas were
      studied histopathologically. Variants of invasive ductal adenocarcinoma and
      intraductal papillary-mucinous carcinoma were excluded. RESULTS: Intraductal
      carcinoma components of invasive ductal adenocarcinoma were found in 12 of the
      specimens 13 (92%), and were observed within the tumor mass and/or on its
      boundary, or outside the tumor mass. Intraductal components were characterized by
      low papillary projections lacking a fibrovascular core, with/without surrounding
      tubular structures, or by irregular stratification and pleomorphism of the
      epithelial cells. Invasive components mostly showed a tubular pattern with
      desmoplasia. The distribution of the intraductal components in the 12 specimens
      was as follows: in 9 (75%), they were in both the main pancreatic duct and large
      branch ducts; and in 3, they were in the smaller branch ducts only. CONCLUSIONS:
      Invasive ductal adenocarcinomas of the pancreas may originate most frequently
      from the main pancreatic duct or larger branch ducts, while the smaller ducts are
      less often the site of cancer origin.

PMID- 17520205
TI  - Predictors of hepatic venous trunk invasion and prognostic factors in patients
      with hepatocellular carcinomas that had come into contact with the trunk of major
      hepatic veins.
AB  - PURPOSE: In this study, we tried to identify the preoperative predictors of
      hepatic venous trunk invasion and the prognostic factors in patients with
      hepatocellular carcinoma (HCC) that had come into contact with the trunk of a
      major hepatic vein over a distance of 1.0 cm or more. METHODS: Forty patients who
      had such HCCs resected were entered into this study and predictors of hepatic
      venous trunk invasion and prognostic factors were evaluated by univariate and
      multivariate analyses. RESULTS AND CONCLUSIONS: A combined resection of the HCC
      and the venous trunk was performed in 29 patients. Hepatic venous trunk invasion
      was observed in 12 patients, including 2 with inferior vena cava tumor thrombus.
      A stepwise logistic regression analysis indicated that tumors larger than or
      equal to 7 cm in diameter and tumors showing a poorly differentiated histological
      grade were independent predictors of hepatic venous trunk invasion. The survival
      of patients without venous trunk invasion was significantly better than that for
      patients with venous trunk invasion (P = 0.048). A univariate analysis revealed
      that Child-Pugh classification B (P = 0.002), a high des-gamma-carboxy
      prothrombin concentration (> or =400 mAU/ml, P = 0.023), a large HCC (> or =5.0
      cm in diameter, P = 0.002), the presence of portal vein invasion (P < 0.001), the
      presence of venous trunk invasion (P = 0.048), the presence of intrahepatic
      metastasis (P < 0.001), and poorly differentiated HCC (P = 0.006) correlated with
      a worse overall survival after hepatic resection. In a multivariate analysis,
      however, only the presence of intrahepatic metastasis (P = 0.037, relative risk
      8.25) was an independent predictor of poor overall survival. CONCLUSIONS: Large
      tumors (> or =7 cm in diameter) and poorly differentiated HCCs were more likely
      to be associated with hepatic venous trunk invasion and intrahepatic metastasis
      was an independent prognostic factor in patients with HCC that had come into
      contact with the trunk of a major hepatic vein.

PMID- 17520206
TI  - Close relation between the inferior vena cava ligament and the caudate lobe in
      the human liver.
AB  - BACKGROUND/PURPOSE: This study was conducted to clarify the real relation between
      the inferior vena cava (IVC) ligament and the caudate lobe in the human liver and
      also to elucidate their surgical importance in liver surgery. METHODS: Specimens
      obtained from 20 adult cadaveric livers were submitted for the study.
      Histological structures of the IVC ligament and its relationship to the caudate
      lobe and the IVC were microscopically investigated. RESULTS: The IVC ligament was
      a broad membranous connective tissue bridging the left and right side edges of
      the caval groove in which the IVC was embedded. At both edges of the caval
      groove, the IVC ligament was continuously transformed from the Glisson's capsules
      of the caudate and right lobes. The component of the portal triad, which
      originated from that of caudate lobe, and lymphatics were distributed in the IVC
      ligament without exception and ectopic hepatocytes existed in it in 4 of the 20
      cases. CONCLUSIONS: A close relation between the IVC ligament and the caudate
      lobe was confirmed. The findings suggested that the IVC ligament is a kind of
      degenerated hepatic tissue. When dissecting it, surgeons should manipulate it
      carefully to prevent unexpected bleeding and bile leakage.

PMID- 17520207
TI  - Temporary pancreatic stent to prevent post endoscopic retrograde
      cholangiopancreatography pancreatitis: a preliminary, single-center, randomized
      controlled trial.
AB  - BACKGROUND: Post endoscopic retrograde cholangiopancreatography (post-ERCP)
      pancreatitis is the most common complication of ERCP, which can occasionally
      become serious or fatal. This preliminary study was to prospectively evaluate the
      efficacy of a temporary unflanged pancreatic duct stent (PS) to prevent post-ERCP
      pancreatitis. METHODS: A total of 64 patients were randomly divided into a
      control group, which did not undergo stenting, and a stent group. The stent used
      was a 5-Fr pigtail PS without an inner flange. RESULTS: Placement of an unflanged
      PS was successful and without complications in all 32 patients. The rates of
      hyperamylasemia were 50.0% and 34.4% in the control and stent groups,
      respectively (P > 0.05), and the mean serum amylase levels were 456.2 and 257.9
      IU/l, respectively (P = 0.035). The overall rates of post-ERCP pancreatitis
      diagnosed according to Cotton's criteria were 12.5% and 3.1% in the control and
      stent groups, respectively (P > 0.05). The severity of pancreatitis was severe in
      one patient, moderate in one, and mild in two in the control group, whereas in
      the stent group, the single case of pancreatitis was mild. CONCLUSIONS: Placement
      of an unflanged 5-Fr PS may be useful in preventing post-ERCP pancreatitis.

PMID- 17520208
TI  - Usefulness of beta-D glucan in diagnosing Pneumocystis carinii pneumonia and
      monitoring its treatment in a living-donor liver-transplant recipient.
AB  - Pneumocystis carinii pneumonia (PCP) is one of the fatal complications
      encountered after liver transplantation. The diagnosis of PCP is sometimes very
      difficult, because detection of the bacteria itself is not easy under some
      conditions, and the serum level of the chemical mediator is not yet considered to
      be a definitive diagnostic marker. We report a case of PCP that occurred 3 months
      after transplantation in a living-donor liver-transplant recipient; the disease
      developed during the course of outpatient follow-up when the patient's condition
      was stable. The patient was maintained with the usual level of
      immunosuppressants, using tacrolimus, steroid, and mycophenolate mofetil. The
      patient had a dry cough with mild fever, and a chest computed tomography (CT)
      scan showed a reticular shadow in the left lung field. The plasma level of beta
      D: glucan was high (135 pg/ml). We suspected an invasive fungal infection, but no
      pathogen was detected by routine fungal culture and cytology. Finally, P. carinii
      was detected by polymerase chain reaction (PCR), and we started treatment with
      trimethoprim-sulfamethoxazole (TMP/SMX) combined with an antifungal agent. During
      this period, the level of beta-D: glucan correlated with the patient's clinical
      symptoms; this marker was very useful for monitoring the treatment of PCP in this
      living-donor liver-transplant recipient.

PMID- 17520209
TI  - Right trisectionectomy of the liver for intrahepatic cholangiocarcinoma with bile
      duct invasion in a Jehovah's Witness.
AB  - Intrahepatic cholangiocarcinoma (ICC) is well known to have a very poor
      prognosis. Aggressive surgical strategies in the treatment of ICC, including
      major hepatectomy, have been reported to afford patients the best chance for
      significant survival. Recent advancements in surgical techniques concerning live
      donor liver transplantation have dramatically improved the results of major
      hepatectomy. However, surgical treatment of biliary malignancy is complex and is
      known to increase the likelihood of blood transfusion. We describe a Jehovah's
      Witness patient with ICC and concomitant bile duct invasion who had a successful
      right trisectionectomy with bile duct resection, lymph node dissection, and
      Rouxen-Y hepatico-jejunostomy without blood transfusion. A multidisciplinary
      preparation was crucial in obtaining this positive outcome. Importantly,
      bloodless liver transection techniques with inflow clamping, meticulous
      dissection, and hemostasis should be utilized for major hepatectomy in a
      Jehovah's Witness. The success of this case may alert clinicians to consider a
      hepatectomy as a possible option in the treatment of ICC in a Jehovah's Witness.

PMID- 17520210
TI  - A malignant nonfunctioning pancreatic endocrine tumor with a unique pattern of
      intraductal growth.
AB  - The intraductal growth of nonfunctioning pancreatic endocrine tumors (NFPTs) is
      considered to be rare, and in our survey of the English-language literature, we
      found only three cases to have been described previously. We herein report the
      case of a 36-year-old man with a malignant NFPT that uniquely grew within the
      lumen of the main pancreatic duct (MPD) and completely obstructed the MPD, as
      shown by endoscopic retrograde pancreatography (ERP). Endoscopic ultrasonography
      clearly detected the tumor with intraductal growth. In addition, positron
      emission tomography (PET), using 18F-fluorodeoxyglucose (FDG) and computed
      tomography (CT) with the same scanner (FDG-PET/CT) showed enhanced uptake of FDG
      in the tumor. A pylorus-preserving pancreaticoduodenectomy and regional
      lymphadenectomy were performed under the preoperative diagnosis of an NFPT.
      Microscopically, positive immunoreactions for synaptophisin and vasoactive
      intestinal peptide indicated neuroendocrine differentiation of the tumor, while
      in addition, metastasis to a lymph node along the common hepatic artery was also
      observed. The patient has survived for 6 months after the surgery without any
      evidence of recurrence or metastasis. Both ERP and FDG-PET/CT were thus found to
      be useful for predicting the malignant potential of an NFPT in the preoperative
      diagnosis.

PMID- 17520211
TI  - Sarcomatous hepatocellular carcinoma without previous anticancer therapy.
AB  - Sarcomatous hepatocellular carcinoma is a rare neoplasm of the liver. A 79-year
      old man with a liver tumor was admitted to our hospital. Enhanced computed
      tomography and magnetic resonance imaging revealed a cystlike lesion, whereas
      abdominal ultrasonography revealed a solid tumor. The patient underwent medial
      segmentectomy of the liver for the presumptive diagnosis of atypical
      hepatocellular carcinoma. Microscopically, the tumor was diagnosed as
      hepatocellular carcinoma with sarcomatous change. Although anticancer therapy is
      presumed to be a cause of sarcomatous change in hepatocellular carcinoma, some
      cases in which patients had not previously undergone anticancer therapy have been
      reported. Here we report a case of sarcomatous hepatocellular carcinoma without
      previous anticancer therapy and present a review of the literature.

PMID- 17520212
TI  - Cutaneous metastasis from hepatocellular carcinoma as the first clinical sign.
AB  - Hepatocellular carcinoma (HCC) is a tumor whose incidence has been increasing in
      recent years. The occurrence of cutaneous metastases from HCC, as the first sign
      of onset, is very unusual. We report a case of cutaneous metastasis from HCC
      appearing as a shoulder abscess and being the first clinical sign of the disease.
      We also examined the few published cases, and the diagnosis, treatment, and
      survival rate for this disease. Metastases of HCC should be included in the
      differential diagnosis of growing lesions in unusual localizations. Biopsies are
      required to confirm the diagnosis. The diagnosis of HCC from a cutaneous lesion
      is very uncommon and is associated with a poor prognosis.

PMID- 17520213
TI  - Late hemorrhage after pancreatoduodenectomy and heavy ion beam therapy.
AB  - The patient was a 57-year-old man diagnosed with cancer of the pancreatic head.
      After treatment by heavy ion beam therapy, pylorus-preserving
      pancreatoduodenectomy was performed. The tumor was pT3, pN0, pM0, stage IIA.
      Sixteen months after the surgery, the patient was admitted to the hospital
      because he was vomiting blood. Hemorrhaging caused by failure of the cut end of
      the gastroduodenal artery into the elevated jejunum was confirmed by angiogram,
      and the hemorrhaging could be stopped by a transcatheter arterial embolization
      operation. Twenty-four months after surgery, the patient was readmitted because
      he was once again vomiting blood. Hemorrhaging from the elevated jejunum was
      suspected by hemorrhagic scintigram, but the source could not be identified on
      further examination, and the choice of treatment was difficult. The patient died
      on the 9th day after admittance to the hospital. Even on examination at autopsy,
      the source of the hemorrhaging could not be identified. No recurrence of cancer
      could be found. This has proven to be a perplexing case, in that hemorrhaging
      from the end of the routinely cut gastroduodenal artery occurred 16 and 24 months
      after heavy ion beam therapy and pylorus-preserving pancreatoduodenectomy for
      pancreatic cancer.

PMID- 17520214
TI  - Necrotizing fasciitis secondary to carcinoma of the gallbladder with perforation.
AB  - We present an unusual case of necrotizing fasciitis in the upper abdominal wall
      caused by penetrating perforation of the gallbladder. It was manifested as an
      elastic and reddish abdominal swelling with severe tenderness, but no peritoneal
      irritation. Computed tomography (CT) demonstrated water density with a slightly
      elevated CT value and air bubbles in the subcutaneous space. The preoperative
      diagnosis was subcutaneous abscess with fasciitis. At surgery, necrotizing
      fasciitis and subcutaneous abscess secondary to penetrating perforation of the
      gallbladder were revealed. Cholecystectomy and peritoneal irrigation were
      performed. Although no tumor was evident during surgery, a tumor located close to
      the perforation site was found just after the operation. Pathological examination
      revealed gallbladder carcinoma without stones. There have been very few previous
      reports of necrotizing fasciitis following gallbladder perforation. The
      presentation, diagnosis, and management of fasciitis, as well as carcinoma of the
      gallbladder with perforation, are discussed.

PMID- 17520215
TI  - Autoimmune pancreatitis: a message from Japan.
AB  - Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis generally
      observed in aged people and characterized by the presence of autoantibodies,(1-3)
      elevated levels of immunoglobulins,(4) enlargement of the pancreas (diffuse or
      focal) on ultrasonography (US) or computed tomography (CT),(1-3,5) diffuse
      narrowing of the main pancreatic duct (MPD) with an irregular wall,(1,3,5-8) and
      pathologic features of dense lymphoplasmacytic inflammation and fibrosis, as well
      as a favorable response to steroid therapy.(1-3,5,8) The clinical findings in AIP
      include obstructive jaundice secondary to biliary stenosis, mild epigastralgia,
      and diabetes mellitus. The clinical, laboratory, and radiological features
      respond promptly to oral steroid therapy.(1-3,5,6,8) Although prompt response to
      oral steroid therapy may be helpful in the differential diagnosis of AIP, careful
      imaging studies are necessary to exclude cancer of the pancreas or common bile
      duct (CBD).

PMID- 17520216
TI  - Prevalence of autoimmune pancreatitis in Japan from a nationwide survey in 2002.
AB  - BACKGROUND: Because autoimmune pancreatitis is a new disease entity, there are no
      data with regard to its prevalence. METHODS: To estimate the number of patients
      with autoimmune pancreatitis in Japan, we randomly selected hospitals using
      stratification and asked them how many patients they had with pancreatitis in
      2002 who fulfilled the diagnostic criteria for autoimmune pancreatitis as
      proposed by the Japan Pancreas Society. RESULTS: The number of patients with
      autoimmune pancreatitis who visited hospitals in Japan in 2002 was approximately
      900 (95% confidence interval; range 670-1100). The male : female ratio was 2.85 :
      1, and the age of disease onset in 95% of the patients was over 45 years.
      CONCLUSIONS: The prevalence of patients with autoimmune pancreatitis in Japan was
      estimated to be 0.82 per 100,000. Autoimmune pancreatitis was predominantly seen
      in men past middle age (over the age of 45 years).

PMID- 17520217
TI  - Clinical features of autoimmune pancreatitis.
AB  - Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by
      a high serum IgG4 concentration, and complications involving various
      extrapancreatic lesions. It should be emphasized that autoimmune pancreatitis is
      easily misdiagnosed as pancreatic cancer. This disease predominantly affects
      elderly men. The major symptom at onset is obstructive jaundice, while severe
      abdominal pain is rare. Blood tests have shown abnormal results, which could be
      attributed mainly to the obstructive jaundice. With regard to autoantibodies, the
      positive rate for the antinuclear antibody is 40%; however, disease-specific
      autoantibodies are rarely found. About half of the patients with autoimmune
      pancreatitis have shown exocrine and endocrine dysfunctions. IgG4 is a sensitive
      and specific marker for diagnosing autoimmune pancreatitis. In differentiating
      between pancreatic cancer and autoimmune pancreatitis, IgG4 shows a sensitivity
      of 90%, a specificity of 98%, and an accuracy of 95%. HLA DRB1*0405-DQB1*0401
      alleles are significantly associated with autoimmune pancreatitis, and may
      present a specific peptide which triggers the autoimmune response. Various
      imaging findings have shown pancreatic swelling, irregular narrowing of the main
      pancreatic duct, and stenosis of the lower bile duct. Histology shows a
      significant presence of lymphocytes, plasma cell infiltration, and fibrosis with
      abundant IgG4-bearing plasma cell infiltration. After corticosteroid treatment,
      imaging findings and pancreatic functions usually improve significantly. It is
      probable that autoimmune pancreatitis is an essentially progressive condition
      resulting in pancreatic stone formation in a similar way to ordinary chronic
      pancreatitis.

PMID- 17520218
TI  - Systemic extrapancreatic lesions associated with autoimmune pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is frequently associated with sclerosing
      cholangitis (SC). SC with AIP has a cholangiographic appearance that is often
      confused with primary sclerosing cholangitis (PSC) but only the former responds
      well to corticosteroid therapy. Detailed study of cholangiographic findings
      allows discrimination of SC with AIP from PSC. Band-like strictures, a beaded or
      pruned-tree appearance, and diverticulum-like outpouching were significantly more
      frequently observed in cases of PSC. In contrast, segmental strictures, dilation
      after confluent stricture, and strictures of the lower common bile duct were
      significantly more common in SC with AIP. The other systemic extrapancreatic
      lesions associated with AIP found in the literature were Sjogren's syndrome,
      ulcerative colitis, retroperitoneal fibrosis, sialadenitis, thyroiditis, and
      idiopathic thrombocytopenic purpura. In a comparison of the clinical course and
      laboratory data of our cases, gamma-globulin, IgG, and IgG4 levels were
      significantly higher in patients with AIP with systemic extrapancreatic lesions
      than those without them. In our immunohistochemical study, marked infiltration of
      IgG4+ plasma cells was frequently observed in the pancreas, liver, bile duct, and
      salivary glands of the AIP patients examined. In contrast, the degree of
      infiltration of IgG4+ plasma cells around the bile duct in the portal areas and
      the extrahepatic bile duct with PSC was significantly lower than with AIP. These
      results also suggest that AIP is a disease state clearly different from PSC. In
      addition, the normal epithelia of the pancreatic ducts, bile ducts, gallbladder,
      and salivary gland ducts reacting with the patients' sera was detectable by the
      anti-IgG4 antibody. Therefore, AIP may also affect extrapancreatic organs, and
      the sera of AIP patients may contain an IgG4 autoantibody to various organs.

PMID- 17520219
TI  - Pathology of autoimmune pancreatitis and tumor-forming pancreatitis.
AB  - The most frequently recognized presentation of autoimmune pancreatitis (AIP) is
      that mimicking pancreatic cancer. It is also known that at some stage during the
      disease process chronic pancreatitis clinically presents as a tumorous swelling,
      often suspected of being a carcinoma. In Japan, this stage has also been proposed
      clinically to be tumor-forming pancreatitis. Hence, tumor-forming pancreatitis
      shows at least two distinct types: a reparative process for centriductal acute
      inflammation with a background of chronic pancreatitis, which is considered to
      have given rise to the tumor at some stage of chronic pancreatitis, and a
      lymphoplasmacytic infiltration with lymphoid and fibrous proliferation in normal
      pancreatic tissue, which corresponds to autoimmune pancreatitis. These tumorous
      lesions may be changeable along the disease process.

PMID- 17520220
TI  - Autoimmune pancreatitis: histo- and immunopathological features.
AB  - In recent years autoimmune pancreatitis (AIP) has been established as a special
      type of chronic pancreatitis. It is characterized by its histopathological and
      immunological features. The morphological hallmarks are periductal infiltration
      by lymphocytes and plasma cells, granulocytic epithelial lesions with focal
      destruction of the duct epithelium, venulitis, and diffuse sclerosis in advanced
      stages. AIP has therefore also been called lymphoplasmacytic sclerosing
      pancreatitis, duct-destructive chronic pancreatitis, or sclerosing pancreatitis.
      AIP most commonly involves the head of the pancreas and the distal bile duct.
      Occasionally it is mass-forming, and has been described as an inflammatory
      myofibroblastic tumor. The presence of more than 20 IgG4-positive plasma cells
      per high-power field is of high specificity for the tissue diagnosis of AIP.

PMID- 17520221
TI  - How to diagnose autoimmune pancreatitis by the revised Japanese clinical
      criteria.
AB  - When diagnosing autoimmune pancreatitis (AIP), it is most important to
      differentiate it from neoplastic lesions such as pancreatic or biliary cancers.
      The revised diagnostic criteria are based on the minimum consensus of AIP in
      order to avoid misdiagnosing pancreas or biliary cancer as far as possible, but
      not for screening AIP. Therefore, it is recommended that facile therapeutic
      diagnosis by steroidal administration should be avoided. These criteria contain
      three approaches: pancreatic imaging, laboratory data, and histopathology. (i)
      Pancreatic image examinations show the narrowing of the main pancreatic duct and
      enlargement of the pancreas, which are characteristic of the disease. (ii)
      Laboratory data show the presence of autoantibodies or elevated levels of serum
      gammaglobulin, IgG, or IgG4. (iii) Histopathologial examinations of the pancreas
      show fibrosis and pronounced infiltration of cells, mainly lymphocytes and
      plasmacytes, which is called lymphoplasmacytic sclerosing cholangitis (LPSP). For
      a diagnosis of AIP, criterion (i) must be present, together with criterion (ii)
      and/or (iii). However, it is necessary to exclude malignant diseases such as
      pancreatic or biliary cancers.

PMID- 17520222
TI  - Diagnosis of autoimmune pancreatitis using its five cardinal features:
      introducing the Mayo Clinic's HISORt criteria.
AB  - Autoimmune pancreatitis (AIP) is a recently defined form of chronic pancreatitis.
      While numerous case reports and small case series of AIP have been reported from
      Japan, there have been relatively few from the West. Based on a retrospective
      review of our experience with resected AIP and a review of the literature, we
      have identified five cardinal features of AIP in histology, imaging, serology,
      other organ involvement, and response to steroid therapy, which are summarized in
      the mnemonic HISORt. A combination of the HISORt criteria can be used to
      definitively diagnose a wide spectrum of manifestations of AIP.

PMID- 17520223
TI  - Diagnostic criteria for autoimmune chronic pancreatitis.
AB  - Autoimmune chronic pancreatitis (AIP) is a clinically attractive entity because
      of its dramatic response to oral steroid therapy. Recently, as awareness of AIP
      is increasing, more cases are being reported. However, there are still no
      established worldwide diagnostic criteria for AIP. Since the Japan Pancreas
      Society (JPS) published diagnostic criteria for autoimmune chronic pancreatitis
      in the year 2002, increased attention toward this relatively new disease entity
      has enabled more cases of AIP to be correctly diagnosed. As previously
      unrecognized or misdiagnosed cases of autoimmune chronic pancreatitis are found,
      an increasing number of cases that are not in full accordance with the JPS
      diagnostic criteria are revealed. As a result, some groups have developed and
      cited their own criteria in the reporting of autoimmune chronic pancreatitis. The
      absence of consistent, uniform criteria has made comparison of different cases
      diagnosed under various guidelines difficult. In this review, we discuss and
      compare the four current sets of diagnostic criteria, focusing on their
      individual strengths and weaknesses.

PMID- 17520224
TI  - Treatment for autoimmune pancreatitis: consensus on the treatment for patients
      with autoimmune pancreatitis in Japan.
AB  - Autoimmune pancreatitis (AIP) has been characterized by unique clinical imaging,
      immunological findings, and the effectiveness of steroid therapy. A set of
      clinicopathological criteria for AIP was proposed by the Japan Pancreatic Society
      in 2002, and AIP has come to be widely recognized among general digestive
      clinicians. However, the indication of steroid therapy for AIP is still not well
      established, and furthermore the therapeutic doses and method of administration
      of steroid therapy is also unclear. Recently, an epidemiological survey of all
      the treatments used for AIP in Japan was conducted by the Research Committee of
      Intractable Pancreatic Diseases, and their report "Consensus for a Treatment of
      Autoimmune Pancreatitis" was produced. In a comparison of the results of steroid
      therapy and nonsteroid therapy for AIP in relation to the rate of complete
      remission, the recurrence rate, and the period needed to guarantee complete
      remission, it was thought that the administration of a steroid should be a
      standard therapy for AIP. However, if the diagnosis of AIP is still uncertain,
      steroid therapy should be given with caution. In addition, even when AIP still
      appears to be possible after a course of steroid therapy, a re-evaluation should
      be carried out taking pancreatic carcinoma into consideration. An initial steroid
      dose of 30-40 mg per day is recommended. With continuous and careful observations
      of the clinical manifestations, laboratory data, and imaging findings after
      administration of the initial dose of steroid for 2-4 weeks, the quantity of
      steroid can be reduced gradually to a maintenance dose in 2-3 months, and then
      reduced to 2.5-5 mg per day after remission. The recommended period of
      maintenance treatment is still unclear, but the administration of the steroid
      could be stopped after a period of about 6-12 months of treatment, although the
      patient should be monitored for clinical manifestations of improvement. In
      addition, the patient's progress should be followed taking recurrence into
      consideration. In order to evaluate the effectiveness of steroid therapy, follow
      up observations should include biochemical examinations of blood findings such as
      serum gamma-globulin, IgG, and IgG 4, imaging findings, and clinical
      manifestations such as jaundice and abdominal discomfort.

PMID- 17520225
TI  - Prognosis of autoimmune pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is responsive to steroid therapy, but some AIP
      patients improve spontaneously, or only improve after biliary drainage.
      Pancreatic enlargement and irregular narrowing of the main pancreatic duct
      usually improves in almost all patients, but marked atrophy of the pancreas
      develops in some patients. Biliary stenosis improves to various degrees, and a
      biliary drainage tube can be withdrawn. Other extrapancreatic lesions, including
      swelling of the salivary or lacrimal glands, lymphadenopathy, and retroperitoneal
      fibrosis also improve with steroid therapy. Pancreatic endocrine and exocrine
      function is frequently impaired in AIP patients, and steroid therapy is
      occasionally effective for these dysfunction. Deterioration of pancreatic
      exocrine function is rarely detected after steroid therapy. In the literature,
      the recurrence rate of AIP was reported to be about 17% (range 6% to 26%). AIP
      patients who relapse during maintenance steroid therapy or after stopping steroid
      medication should be re-treated with a high-dose steroid. Although AIP is rarely
      associated with pancreatic stones, stones are formed in some relapsing AIP
      patients. The long-term prognosis for AIP is unknown. As the pancreatic exocrine
      and endocrine functions as well as the morphological findings are reversible
      after steroid therapy, the prognosis for AIP seems better than that of chronic
      pancreatitis, which is usually followed by exocrine and endocrine pancreatic
      insufficiency with disease progression. Although carcinogenesis of AIP is
      unknown, some AIP patients developed a malignancy during follow-up. Since AIP
      occurs predominantly in the elderly, clinicians should pay attention to any
      complicating diseases in follow-up of AIP patients. Further studies are necessary
      to clarify the pathogenesis as well as the long-term prognosis of AIP.

PMID- 17520226
TI  - [Continuous intrathecal administration of medication. Special features in
      anaesthesiology and intensive care].
AB  - In anaesthesiological and intensive care practice patients are increasingly being
      treated with implanted medication pumps. Basic knowledge on the special aspects
      of this form of therapy is therefore important. During the preanasthesiology
      visit, information on the pump, the intrathecal catheter, type and dosage of the
      medication as well as the next scheduled refilling must be collected and
      documented. Needle punctures near the pump and the catheter must be avoided.
      During intensive care treatment any possible interaction and overdosing or
      underdosing of the intrathecally administered medication must be considered.
      Information on the schedule and punctual organisation of refilling are important
      to avoid complications.

PMID- 17520227
TI  - [Placenta praevia totalis et increta. Cause of life-threatening haemorrhaging
      during a caesarean section].
AB  - Placenta increta is a rare but potentially life-threatening risk constellation
      after a previous caesarean section. We present the case of a 29-year-old gravida
      2 para 1 patient, who developed dramatic haemorrhaging caused by this abnormal
      placentation, which could only be resolved by a postpartal hysterectomy. This
      demonstrates that in the case of a combination of the two most common
      predisposing factors, repeat caesarean section and placenta praevia, the
      possibility of a placenta increta should be considered and suitable precautions
      should be taken.

PMID- 17520228
TI  - [Postoperative nausea and vomiting].
AB  - The rule of three describes three steps which are needed for an optimal control
      of postoperative nausea and vomiting (PONV). Firstly, patients at high risk of
      PONV need to be identified. Knowledge about predictive factors may help to
      identify patients who may best profit from prophylaxis and those where
      prophylaxis is not worthwhile since the baseline risk is too low. Secondly, for
      high-risk patients a low emetogenic anaesthesia technique should be chosen, and
      thirdly, these patients should additionally receive a prophylactic antiemetic
      cocktail. At present, butyrophenones (e.g. droperidol), 5-HT(3) receptor
      antagonists ("setrons") and steroids (e.g. dexamethasone) are the most rational
      choices for the antiemetic cocktail. Although there is strong evidence that there
      is an additive effect when these antiemetics are combined, economic constraints
      may influence the number of antiemetics that are eventually chosen.
      Identification of high-risk patients remains the most difficult part of the rule
      of three. Risk scores have been proposed and have been widely implemented in
      clinical practice. The sensitivity and specificity of such scores, however,
      remain particularly unsatisfactory. Unless more reliable risk scores are
      developed, aggressive treatment of established PONV symptoms may be more useful
      and more cost-effective than prophylaxis for many patients.

PMID- 17520230
TI  - [Minimally invasive surgery. Economic analyses from the view point of the
      sickness funds].
AB  - Minimally invasive surgery (MIS) claims to lead to less pain, faster recovery
      and/or healing, smaller scars and a shorter hospital stay, ideally in combination
      with lower costs. This article discusses which aspects of the economic evaluation
      of MIS, from the perspective of the statutory health insurance (SHI), are
      relevant. The economic perspective of the statutory health insurance primarily
      comprises the expenditures for illness (e.g. medical treatment, drugs,
      rehabilitation, sick-pay), i.e. direct costs only. Indirect costs (i.e.
      productivity losses) remain unconsidered. Thus, the perspective of the SHI
      describes only a reduced view of reality. However, on the basis of proven
      efficacy, cost-minimisation and cost-benefit analyses for certain questions are
      conceivable from the perspective of the SHI. Results from such analyses can
      generate important information for the calculation of tariffs and negotiation of
      contracts.

PMID- 17520229
TI  - [Laryngeal masks. Possibilities and limits].
AB  - Introduction of the laryngeal mask airway (LMA) has been a revolutionary
      development in airway management over the last decades. It was first used
      clinically in 1981 by A. Brain and has been widely used in Germany since 1990.
      Originally intended as a substitute for conventional mask respiration for short
      periods of general anaesthesia, the laryngeal mask is in the meantime used in
      many areas as an alternative to elective endotracheal intubation as well as an
      option for controlling difficult airways. This contribution provides an overview
      of the basics as well as practical aspects of LMA use, and discusses the
      possibilities and limitations of the laryngeal mask in daily practice.

PMID- 17520231
TI  - [The present and future status of "scarless" surgery].
AB  - The concept of scarless surgery aims at further minimization of diagnostic and
      therapeutic interventions. Based on the success of flexible gastroenterological
      endoscopy and laparoscopic surgery, it combines their advantageous approaches in
      a synergistic manner. Animal experiments have achieved encouraging results in
      respect to the feasibility of various types of interventions in the peritoneal
      and retroperitoneal cavity. Further studies and improvement of instruments will
      have to prove the practicality and superiority of this concept for medical
      outcome and efficiency compared to present standards of practice in the potential
      fields of application. The replacement of certain minimally invasive procedures
      with scarless intervention techniques seems reasonable, as do new fields of
      application. After further improvement of the methodology, adequate organization,
      infrastructure, and teaching structures will have to be developed. If they
      succeed, the concept of scarless surgery can expect a promising future.

PMID- 17520232
TI  - [The influence of navigation on endoscopic sinus surgery].
AB  - BACKGROUND: Over the last few years, navigation systems have been used in
      endoscopic sinus surgery (ESS). We were interested determining whether this has
      repercussions on surgical procedures. MATERIAL AND METHODS: From December 2003 to
      April 2006, we prospectively evaluated all navigated ESS procedures (Vector
      vision, Brain lab) by means of a questionnaire. Numerous data were determined
      including diagnosis, navigation benefit, difficulty of the operation,
      radiological score and complications. RESULTS: Navigated ESS was carried out on
      106 patients (54 male symbol; 52 female symbol, average age 55 years) with the
      following diagnoses: 59 chronic sinusitis with nasal polyposis (13 primary
      surgery, 46 revision surgery), 14 mucocele, 8 benign tumour, 10 malignant
      sinonasal tumour, and 15 other diseases. There was only a slight correlation
      between the difficulty of the operation and the use of navigation (r=0.51,
      P=0.00) and no significant correlation between the radiological score with
      chronic sinusitis and the use of navigation (r=0.22, P=1.23). On the other hand,
      we found a significant difference between the benefit of navigation using primary
      and revision functional ESS in cases of chronic sinusitis with nasal polyps
      (P=0.005). The degree of benefit of navigation for the different diagnoses was in
      descending order: recurrent polyposis, mucocele, osteoma, malignant tumors,
      polyposis (primary surgery) and inverted papilloma. Without navigation, 15
      operations (14%) would not have been possible as an endonasal procedure, and 12
      operations (11%) would not have been carried out thoroughly enough. In spite of
      navigation in three operations (3%) the endonasal approach had to be changed to a
      transfacial approach. Twelve slight and three serious complications (1 dura
      defect + pneumoencephalos, dura defect, meningitis without CSF leak) occurred.
      CONCLUSIONS: Navigation exerts a substantial influence on the execution of the
      ESS by clearly extending its possibilities.

PMID- 17520233
TI  - [The binaural interaction component: a clinically useful diagnostic instrument?].

PMID- 17520234
TI  - [Early evaluation of neurological prognosis and therapy after cardiopulmonary
      resuscitation: current opportunities and clinical implications].
AB  - The developments of cardiopulmonary resuscitation and intensive care medicine
      have made possible survival after cardiac arrest. However, only 10-30% of
      patients with initially successful resuscitation later reach a state without
      severe neurological impairment. Ethical and socioeconomic reasons therefore make
      early prognosis important for certain patients. There are no reliable parameters
      for predictions of good clinical outcome. If clinical information is consistent
      with severe hypoxic brain damage, cortical somatosensory evoked potentials are
      absent, and neuron-specific enolase values exceed 33-65 microg/l, recovery of
      consciousness can be excluded. The same result can be predicted if brain imaging
      shows severe hypoxemic changes or if a myoclonic status occurs on the first day.
      In summary, the prognosis in patients with cerebral anoxy and cardiopulmonary
      resuscitation remains poor. Treatment with hypothermia for 24 h is recommended.

PMID- 17520237
TI  - Combined effect of pioglitazone and simvastatin on urinary liver-type fatty acid
      binding protein concentration in diabetic patients with microalbuminuria.

PMID- 17520236
TI  - [Long-term follow-up on alcohol use in a big company after brief intervention by
      a company physician].
AB  - BACKGROUND: Many examinations have shown that brief medical interventions are
      useful when seeking to influence the drinking behavior of problem drinkers and
      alcohol-dependent subjects. The working environment is particularly useful when
      trying to influence problematic drinking behavior. Our report is about the long
      term effects on alcoholic employees. METHODS: The drinking behavior of 100
      employees was categorized according to WHO criteria. By motivational
      interviewing, the employees were asked to reduce their alcohol consumption or
      quit completely and then come back at a later control date. The data collected
      was: drinking behavior (TLFB, time-line follow-back), biological markers (GGT,
      CDT, MCV), changes in personal situations, and the factors and reasons involved.
      RESULTS: Forty-five percent of the employees went to their company physician
      after recommendation by their supervisors, and 24% went on their own initiative.
      Of the employees examined, 82% were diagnosed as being alcohol-dependent, 4% as
      harmful abusers, 6% as risky drinkers, and 8% as questionably risky drinkers. At
      the time of catamnesis, 78% of the employees that were originally diagnosed as
      alcohol-dependent were abstinent. Of those participants, 17% that were initially
      classified as not dependent were abstinent, and the overall quantity of alcohol
      consumed was also reduced significantly by 79.3%. Personal realms especially
      concerning happiness in life, happiness at work, and physical health improved.
      CONCLUSION: The results show that a brief medical intervention conducted by a
      company physician is suited to influencing the drinking behavior of employees
      effectively and efficiently. The fear of demotion at work and job loss may prove
      to be a helpful influence on changing drinking behavior.

PMID- 17520238
TI  - Effects of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma
      agonists on glucose and lipid metabolism in patients with type 2 diabetes
      mellitus.
AB  - AIMS/HYPOTHESIS: The aim of the study was to examine the effects of pioglitazone
      (PIO), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, and
      fenofibrate (FENO), a PPAR-alpha agonist, as monotherapy and in combination on
      glucose and lipid metabolism. SUBJECTS AND METHODS: Fifteen type 2 diabetic
      patients received FENO (n = 8) or PIO (n = 7) for 3 months, followed by the
      addition of the other agent for 3 months in an open-label study. Subjects
      received a 4 h hyperinsulinaemic-euglycaemic clamp and a hepatic fat content
      measurement at 0, 3 and 6 months. RESULTS: Following PIO, fasting plasma glucose
      (FPG) (p < 0.05) and HbA(1c) (p < 0.01) decreased, while plasma adiponectin (AD)
      (5.5 +/- 0.9 to 13.8 +/- 3.5 microg/ml [SEM], p < 0.03) and the rate of insulin
      stimulated total-body glucose disposal (R (d)) (23.8 +/- 3.8 to 40.5 +/- 4.4
      micromol kg(-1) min(-1), p < 0.005) increased. After FENO, FPG, HbA(1c), AD and R
      (d) did not change. PIO reduced fasting NEFA (784 +/- 53 to 546 +/- 43
      micromol/l, p < 0.05), triacylglycerol (2.12 +/- 0.28 to 1.61 +/- 0.22 mmol/l, p
      < 0.05) and hepatic fat content (20.4 +/- 4.8 to 10.2 +/- 2.5%, p < 0.02).
      Following FENO, fasting NEFA and hepatic fat content did not change, while
      triacylglycerol decreased (2.20 +/- 0.14 to 1.59 +/- 0.13 mmol/l, p < 0.01).
      Addition of FENO to PIO had no effect on R (d), FPG, HbA(1c), NEFA, hepatic fat
      content or AD, but triacylglycerol decreased (1.61 +/- 0.22 to 1.00 +/- 0.15
      mmol/l, p < 0.05). Addition of PIO to FENO increased R (d) (24.9 +/- 4.4 to 36.1
      +/- 2.2 micromol kg(-1) min(-1), p < 0.005) and AD (4.1 +/- 0.8 to 13.1 +/- 2.5
      microg/ml, p < 0.005) and reduced FPG (p < 0.05), HbA(1c) (p < 0.05), NEFA (p <
      0.01), hepatic fat content (18.3 +/- 3.1 to 13.5 +/- 2.1%, p < 0.03) and
      triacylglycerol (1.59 +/- 0.13 to 0.96 +/- 0.9 mmol/l, p < 0.01). Muscle
      adenosine 5'-monophosphate-activated protein kinase (AMPK) activity did not
      change following FENO; following the addition of PIO, muscle AMPK activity
      increased significantly (phosphorylated AMPK:total AMPK ratio 1.2 +/- 0.2 to 2.2
      +/- 0.3, p < 0.01). CONCLUSIONS/INTERPRETATION: We conclude that PPAR-alpha
      therapy has no effect on NEFA or glucose metabolism and that addition of a PPAR
      alpha agonist to a PPAR-gamma agent causes a further decrease in plasma
      triacylglycerol, but has no effect on NEFA or glucose metabolism.

PMID- 17520239
TI  - Meta-analysis does not allow appraisal of complex interventions in diabetes and
      hypertension self-management: a methodological review.
AB  - Common methodologies used in systematic reviews do not allow adequate appraisal
      of complex interventions. The aim of the present study was to describe and
      critically appraise current methods of systematic reviews on complex
      interventions, using diabetes and hypertension patient education as examples.
      PubMed, the Cumulative Index to Nursing and Allied Health (CINAHL), the Cochrane
      Library and Health Technology Assessment databases were searched. Systematic
      reviews focusing on diabetes or hypertension patient education were included.
      Authors were contacted. Two investigators independently evaluated the reviews.
      The available evidence of three patient education programmes of diabetes and
      hypertension self-management implemented in Germany was used as a reference. We
      included 14 reviews; 12 reviews mentioned that the included education programmes
      were multidimensional. Reviews on comparable topics identified different
      publications of the same programme. Identical programmes were classified
      differently within and between reviews. Education programmes were dissected to
      analyse effects of single components. Different components of identical
      programmes were used. Interdependencies between components were not explored. Six
      reviews performed meta-analysis across programmes with heterogeneous educational
      or organisational approaches. The complexity of efficacy measures was
      disregarded: e.g. HbA(1c) was used as an isolated outcome variable without
      considering treatment goals, effects on hypoglycaemia, body weight or quality of
      life. Our results indicate that methods of current systematic reviews are not
      fully equipped to appraise patient education and self-management programmes.
      Since these are complex and heterogeneous interventions, consideration of
      aggregated evidence is necessary.

PMID- 17520240
TI  - Effects of SO2 derivatives on expressions of MUC5AC and IL-13 in human bronchial
      epithelial cells.
AB  - Sulfur dioxide (SO2) is a common air pollutant, and inhaled SO2 in airway
      epithelium easily forms its soluble derivatives in vivo (bisulfite and sulfite),
      which are toxic to the respiratory system and related to the exacerbation of
      asthma. To investigate the effects of SO2 derivatives on the expressions of
      asthma related genes (MUC5AC and IL-13), the mRNA and protein levels of the two
      genes in cultured human bronchial epithelial (BEP2D) cells were analyzed using
      real-time reverse transcription-polymerase chain reaction (real-time RT-PCR)
      assay, immunocytochemistry method and enzyme-linked immunosorbent assay (ELISA),
      respectively. The results showed that the mRNA expressions of MUC5AC and IL-13
      were significantly increased at different concentrations of SO2 derivatives
      (0.0001, 0.001, 0.01, 0.1 and 1.0 mM), and the maximum appeared at 0.01 mM for
      MUC5AC (3.9-fold) or at 0.001 mM for IL-13 (4.7-fold). Meanwhile, SO2 derivatives
      significantly increased the mRNA levels at 0, 0.5, 1, 4 and 24 h post-exposure
      with the maximum at 4 h post-exposure (25-fold for MUC5AC and 41-fold for IL-13).
      Furthermore, the protein levels of MUC5AC and IL-13 in BEP2D cells were
      significantly increased at different concentrations and different time courses
      exposed to SO2 derivatives, along with the maximum at 4 h post-exposure. These
      results lead to a conclusion that SO2 derivatives can increase the expressions of
      MUC5AC and IL-13 genes on the transcription and translation levels, and it
      suggests that SO2 derivatives can induce mucus over-production and inflammation
      responses in human bronchial epithelial cells and may have relations with asthma
      diseases. This might be one of the possible mechanisms that SO2 aggravates asthma
      disease.

PMID- 17520241
TI  - Pavlovian conditioning of an approach bias in low-dependent smokers.
AB  - RATIONALE: In the present study, it was investigated whether smokers can acquire
      a behavioural approach bias through Pavlovian conditioning. OBJECTIVES: More
      specifically, it was tested whether pairing neutral stimuli with either smoking
      availability or unavailability would lead to both differential urge responding to
      these stimuli and a corresponding shift in approach bias. MATERIALS AND METHODS:
      Thirty-nine low-dependent smokers performed a stimulus-response compatibility
      (SRC) task with which one can determine an approach bias. Next, participants
      received a conditioning session in which one cue (either a blue or yellow
      background screen colour) was paired with the opportunity to smoke (CS+) and
      another cue was paired with the absence of the opportunity to smoke (CS-). After
      conditioning, all participants again performed the SRC task. RESULTS: Evidence
      for the conditioning of an approach bias but not smoking urges was found. This
      effect, although, was only apparent when smokers had been prompted to determine
      the contingency between the cues and smoking outcome. CONCLUSIONS: It is
      concluded that one can differentially condition an approach bias in low-dependent
      smokers.

PMID- 17520242
TI  - Current role of LC-MS in therapeutic drug monitoring.
AB  - The role of liquid chromatography coupled with mass spectrometry (LC-MS)
      techniques in routine therapeutic drug monitoring activity is becoming
      increasingly important. This paper reviews LC-MS methods published in the last
      few years for certain classes of drugs subject to therapeutic drug monitoring:
      immunosuppressants, antifungal drugs, antiretroviral drugs, antidepressants and
      antipsychotics. For each class of compounds, we focussed on the most interesting
      methods and evaluated the current role of LC-MS in therapeutic drug monitoring.

PMID- 17520243
TI  - Autism and urinary exogenous neuropeptides: development of an on-line SPE-HPLC
      tandem mass spectrometry method to test the opioid excess theory.
AB  - Autism is a complex neurodevelopmental disorder with unknown etiology. One
      hypothesis regarding etiology in autism is the "opioid peptide excess" theory
      that postulates that excessive amounts of exogenous opioid-like peptides derived
      from dietary proteins are detectable in urine and that these compounds may be
      pathophysiologically important in autism. A selective LC-MS/MS method was
      developed to analyze gliadinomorphin, beta-casomorphin, deltorphin 1, and
      deltorphin 2 in urine. The method is based on on-line SPE extraction of the
      neuropeptides from urine, column switching, and subsequent HPLC analysis. A limit
      of detection of 0.25 ng/mL was achieved for all analytes. Analyte recovery rates
      from urine ranged between 78% and 94%, with relative standard deviations of 0.2
      6.8%. The method was used to screen 69 urine samples from children with and
      without autism spectrum disorders for the occurrence of neuropeptides. The target
      neuropeptides were not detected above the detection limit in either sample set.

PMID- 17520244
TI  - Periodic increases in force during sustained contraction reduce fatigue and
      facilitate spatial redistribution of trapezius muscle activity.
AB  - This study compared fatigue and the spatial distribution of upper trapezius
      electromyographic (EMG) amplitude during a 6-min constant force shoulder
      elevation task at 20% of the maximal voluntary contraction force (MVC) (constant
      force) and during the same task interrupted by brief (2 s) periodic increases in
      force to 25% MVC every 30 s (variable force). Surface EMG signals were recorded
      with a 13 x 5 grid of electrodes from the upper trapezius muscle of nine healthy
      subjects. The centroid (center of activity) of the EMG root mean square map was
      computed to assess changes over time in the spatial distribution of EMG
      amplitude. MVC force decreased by (mean +/- SD) 9.0 +/- 3.9% after the constant
      force task (P < 0.05) but was unchanged following the variable force contraction.
      The centroid of EMG amplitude shifted in the cranial direction across the
      duration of the variable force contraction (P < 0.05) but not during the constant
      force contraction (shift of 2.9 +/- 2.3 mm and 1.4 +/- 1.1 mm, respectively). The
      results demonstrate that periodic increases in force during a sustained
      contraction enhance the modifications in spatial distribution of upper trapezius
      EMG amplitude and reduce fatigue compared to a constant force contraction
      performed at a lower average load. The change in spatial distribution of EMG
      amplitude over time during a sustained contraction may reflect a mechanism to
      counteract fatigue during prolonged muscle activity.

PMID- 17520245
TI  - Childhood acute pyelonephritis: comparison of power Doppler sonography and Tc
      DMSA scintigraphy.
AB  - BACKGROUND: Tc 99m DMSA scintigraphy is regarded as the gold standard for the
      detection and localization of acute pyelonephritis (APN) in children. Power
      Doppler sonography (PD US) is a radiation-free and cost-effective technique that
      could be useful in the diagnosis of APN in children. OBJECTIVE: To compare the
      predictive value of PD US with DMSA scintigraphy in the diagnosis of APN in
      children. MATERIALS AND METHODS: A total of 74 neonates and children with
      clinical findings consistent with possible upper urinary tract infection were
      evaluated with PD US and DMSA scintigraphy. Children with anatomic (grey-scale)
      abnormalities were excluded. A total of 147 kidneys were examined within the
      first 48 h after the onset of symptoms. Each kidney was divided into three zones
      (upper, middle, and lower third). RESULTS: APN was diagnosed by PD US in 46
      kidneys. Sensitivity and specificity for detecting APN using DMSA scintigraphy as
      the reference standard were 73.8% and 85.7%, respectively. There was good
      agreement between PD US and DMSA scintigraphy in the localization of lesions.
      CONCLUSION: In clinically suspected APN, PD US has acceptable specificity and
      sensitivity, if performed within the first 48 h and could be helpful in neonates
      and children under 3 months of age in whom the use of scintigraphy is generally
      discouraged.

PMID- 17520246
TI  - Voiding urosonography as first step in the diagnosis of vesicoureteral reflux in
      children: a clinical experience.
AB  - BACKGROUND: Contrast-enhanced voiding urosonography (VUS) is becoming more widely
      used for the diagnosis of vesicoureteric reflux (VUR), but until now its use has
      only been accepted for first diagnosis in females and in the follow-up of
      children, including boys, who have already undergone voiding cystourethrography
      (VCUG). OBJECTIVE: To describe our 6-year experience with VUS used as a first
      step in the diagnosis of VUR. MATERIALS AND METHODS: A total of 610 children (334
      boys, 276 girls; mean age 22 months), underwent VUS as the first step in the
      diagnosis of VUR. In selected children, VCUG was also performed. RESULTS: VUR was
      detected in 199 of 610 VUS examinations, and 265 refluxing kidney-ureter units
      were found. Children with VUR underwent antibiotic prophylaxis or surgery.
      Children without VUR underwent clinical follow-up. Just 60 children underwent
      VCUG. The criteria for VCUG were: high-grade VUR after consultation with a
      urologist, onset of urinary tract infection while receiving prophylaxis,
      nondiagnostic VUS, and other malformations with or without clinical signs.
      CONCLUSION: Our experience suggests that we can use VUS as the first step in the
      diagnosis of VUR in children, boys and girls, with a significant reduction in
      radiation exposure.

PMID- 17520247
TI  - Bifunctional enzyme fusion of 3-hexulose-6-phosphate synthase and 6-phospho-3
      hexuloisomerase.
AB  - The formaldehyde-fixing enzymes, 3-Hexulose-6-phosphate synthase (HPS) and 6
      phospho-3-hexuloisomerase (PHI), are the key enzymes catalyzing sequential
      reactions in the ribulose monophosphate (RuMP) pathway. In this study, we
      generated two fused gene constructs of the hps and phi genes (i.e., hps-phi and
      phi-hps) from a methylotrophic bacterium Mycobacterium gastri MB19. The gene
      product of hps-phi exhibited both HPS and PHI activities at room temperature and
      catalyzed the sequential reactions more efficiently than a simple mixture of the
      individual enzymes. The gene product of phi-hps failed to display any enzyme
      activity. Escherichia coli strains harboring the hps-phi gene consumed
      formaldehyde more efficiently and exhibited better growth in a formaldehyde
      containing medium than the host strain. Our results demonstrate that the
      engineered fusion gene has the possibility to be used to establish a formaldehyde
      resistance detoxification system in various organisms.

PMID- 17520248
TI  - Production of uridine 5'-monophosphate by Corynebacterium ammoniagenes ATCC 6872
      using a statistically improved biocatalytic process.
AB  - Attempts were made with success to develop a two-step biocatalytic process for
      uridine 5'-monophosphate (UMP) production from orotic acid by Corynebacterium
      ammoniagenes ATCC 6872: the strain was first cultivated in a high salt mineral
      medium, and then cells were harvested and used as the catalyst in the UMP
      production reaction. Effects of cultivation and reaction conditions on UMP
      production were investigated. The cells exhibited the highest biocatalytic
      ability when cultivated in a medium containing corn steep liquor at pH 7.0 for 15
      h in the exponential phase of growth. To optimize the reaction, both "one-factor
      at-a-time" method and statistical method were performed. By "one-factor-at-a
      time" optimization, orotic acid, glucose, phosphate ion (equimolar KH(2)PO(4) and
      K(2)HPO(4)), MgCl(2), Triton X-100 were shown to be the optimum components for
      the biocatalytic reaction. Phosphate ion and C. ammoniagenes cell were
      furthermore demonstrated as the most important main effects on UMP production by
      Plackett-Burman design, indicating that 5-phosphoribosyl-1-pyrophosphate (PRPP)
      synthesis was the rate-limiting step for pyrimidine nucleotides production.
      Optimization by a central composition design (CCD) was then performed, and up to
      32 mM (10.4 g l(-1)) UMP was accumulated in 24 h from 38.5 mM (6 g l(-1)) orotic
      acid. The yield was threefold higher than the original UMP yield before
      optimization.

PMID- 17520249
TI  - Functional analysis of very long-chain fatty acid elongase gene, HpELO2, in the
      methylotrophic yeast Hansenula polymorpha.
AB  - We describe the cloning and functional characterization of the fatty acid
      elongase gene HpELO2, a homologue of the HpELO1 gene required for the production
      of C24:0 in the yeast Hansenula polymorpha. The open reading frame (ORF) of
      HpELO2 consists of 1,035 bp, encoding 344 amino acids, sharing about 65% identity
      with that of Saccharomyces cerevisiae Elo2. Expression of HpELO2 rescued the
      lethality of the S. cerevisiae elo2Delta elo3Delta double disruptant. An
      accumulation of C18:0 and a significant increase and decrease in the levels of
      C24:0 and C26:0, respectively, were observed in the Hpelo2Delta disruptant. These
      results supported an idea that HpELO2 encodes a fatty acid elongase involved in
      the elongation of C18:0 to very long-chain fatty acids. The Hpelo1Delta
      Hpelo2Delta double disruption was nonviable, suggesting that HpELO1 and HpELO2
      are the only two genes necessary for the biosynthesis in H. polymorpha.
      Interestingly, transcription of HpELO2 and HpELO1 were found to be transiently up
      regulated by exogenous long-chain fatty acids; however, this up-regulation was
      not observed with HpELO1 and HpELO2 genes driven by the constitutively expressed
      promoter of the HpACT gene, suggesting that exogenous fatty acids specifically
      trigger the transcriptional induction of HpELO1 and HpELO2 through their promoter
      regions.

PMID- 17520250
TI  - Partial volume effect-corrected FDG PET and grey matter volume loss in patients
      with mild Alzheimer's disease.
AB  - PURPOSE: Although( 18)F-fluorodeoxyglucose (FDG) PET is an established imaging
      technique to assess brain glucose utilisation, accurate measurement of tracer
      concentration is confounded by the presence of partial volume effect (PVE) due to
      the limited spatial resolution of PET, which is particularly true in atrophic
      brains such as those encountered in patients with Alzheimer's disease (AD). Our
      aim was to investigate the effects of PVE correction on FDG PET in conjunction
      with voxel-based morphometry (VBM) in patients with mild AD. METHODS: Thirty-nine
      AD patients and 73 controls underwent FDG PET and MRI. The PVE-corrected grey
      matter PET images were obtained using an MRI-based three-compartment method.
      Additionally, the results of PET were compared with grey matter loss detected by
      VBM. RESULTS: Before PVE correction, reduced FDG uptake was observed in posterior
      cingulate gyri (PCG) and parieto-temporal lobes (PTL) in AD patients, which
      persisted after PVE correction. Notably, PVE correction revealed relatively
      preserved FDG uptake in hippocampal areas, despite the grey matter loss in medial
      temporal lobe (MTL) revealed by VBM. CONCLUSION: FDG uptake in PCG and PTL is
      reduced in AD regardless of whether or not PVE correction is applied, supporting
      the notion that the reduced FDG uptake in these areas is not the result of
      atrophy. Furthermore, FDG uptake by grey matter tissue in the MTL, including
      hippocampal areas, is relatively preserved, suggesting that compensatory
      mechanisms may play a role in patients with mild AD.

PMID- 17520251
TI  - Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients
      with neuroendocrine tumours.
AB  - PURPOSE: Neuroendocrine tumours (NETs) can be imaged with scintigraphy using
      radiolabelled somatostatin analogues. The aim of our study was to compare the
      value of (68)Ga-DOTATOC PET and (111)In-DTPAOC SPECT (Octreoscan) in the
      detection of NET manifestations. METHODS: Twenty-seven NET patients were
      prospectively examined. (68)Ga-DOTATOC PET and (111)In-DTPAOC SPECT were
      performed using standard techniques. Treatment was not applied in between. Mean
      and maximum standardised uptake values (SUVs) were calculated for PET findings.
      Tumour/non-tumour ratios were calculated for SPECT findings. Findings were
      compared by a region-by-region analysis and verified with histopathology, CT and
      MRI within 21 days. RESULTS: SUVs of positive lesions on (68)Ga-DOTATOC PET
      ranged from 0.7 to 29.3 (mean SUV) and from 0.9 to 34.4 (maximum SUV). Tumour/non
      tumour ratios on (111)In-DTPAOC SPECT ranged from 1.8 to 7.3. In imaging lung and
      skeletal manifestations, (68)Ga-DOTATOC PET was more efficient than (111)In
      DTPAOC SPECT. All discrepant lung findings and 77.8% of discrepant osseous
      findings were verified as true positive PET interpretations. In regional
      comparison of liver and brain, (68)Ga-DOTATOC PET and (111)In-DTPAOC SPECT were
      identical. In lymph nodes, the pancreas and the gastro-intestinal system,
      different values of the two techniques were not indicated in regional analyses.
      In a single patient, surgical interventions were changed on the basis of (68)Ga
      DOTATOC PET findings. CONCLUSION: (68)Ga-DOTATOC PET is superior to (111)In
      DTPAOC SPECT in the detection of NET manifestations in the lung and skeleton and
      similar for the detection of NET manifestations in the liver and brain. (68)Ga
      DOTATOC PET is advantageous in guiding the clinical management.

PMID- 17520253
TI  - A late phase II study of S-1 for metastatic pancreatic cancer.
AB  - This study evaluated the antitumor effect and safety of S-1, an oral
      fluoropyrimidine derivative, in patients with metastatic pancreatic cancer. Chemo
      naive patients with pancreatic adenocarcinoma, and measurable metastatic lesions
      were enrolled. S-1 was administered orally twice daily after meals at a dose of
      80, 100, or 120 mg/day for body surface areas (BSAs) of less than 1.25 m(2),
      between 1.25 m(2) and less than 1.5, or 1.5 m(2) or greater, respectively, for 28
      consecutive days, followed by a 14-day rest. Fifteen (37.5%) of 40 patients
      responded to treatment, including 1 complete response and 14 partial responses.
      The median time to progression and the overall survival time were 3.7 months (95%
      confidence interval, 2.2-5.6 months) and 9.2 months (95% confidence interval, 7.5
      10.8 months), respectively. The major adverse events were anorexia, fatigue,
      hemoglobin reduction, nausea and pigmentation change, although most were
      tolerable and reversible. Although disseminated intravascular coagulation
      occurred in two patients, the condition resolved with anticoagulant therapy. S-1
      is an effective and well-tolerated drug. The effectiveness of this drug should be
      confirmed in a phase III study.

PMID- 17520252
TI  - A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer
      after failure of fluoropyrimidine and platinum combination chemotherapy.
AB  - PURPOSE: Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been
      widely used as a first-line treatment of advanced gastric cancer (AGC). Docetaxel
      has shown promising activity against this disease. In this study, we explored the
      efficacy and safety of docetaxel monotherapy as salvage chemotherapy in AGC after
      F and P combination chemotherapy failed. MATERIALS AND METHODS: From October 2004
      to October 2005, 49 eligible patients were enrolled in this study. The median
      treatment-free interval was 28.0 days, and 81.6% of patients had suffered cancer
      progression within 4 months after the withdrawal of first-line chemotherapy.
      Docetaxel was given IV at a dose of 75 mg/m(2) every 3 weeks, together with
      dexamethasone prophylaxis. RESULTS: A total of 182 cycles of docetaxel were
      administered with a median of 3 (range 1-9) cycles. From an intention-to-treat
      analysis, eight patients achieved objective response with a response rate of
      16.3% (95% CI, 6.0-26.6). The median response duration was 4.7 months. A total of
      20 patients showed stable disease, but 17 patients suffered disease progression.
      At a median follow-up duration of 11.3 months for surviving patients (range 6.3
      18.8 months), the median time to disease progression was 2.5 months (95% CI, 2.3
      2.7) and the median overall survival time since the start of docetaxel
      monotherapy was 8.3 months (95% CI, 6.7-9.8). Grade 3/4 neutropenia and febrile
      neutropenia occurred in 18.4% of patients and in 5.4% of cycles. The incidence of
      non-hematologic toxicities of grade 3 or worse was asthenia 32.7%, diarrhea 10.2%
      and peripheral sensory neuropathy 8.2%. CONCLUSION: Docetaxel at 75 mg/m(2) is
      active against AGC as second-line chemotherapy after prior exposure to F and P
      combination chemotherapy. The toxicity profile is moderate.

PMID- 17520254
TI  - Expression level of thymidylate synthase mRNA reflects 5-fluorouracil sensitivity
      with low dose and long duration in primary colorectal cancer.
AB  - OBJECTIVES: To investigate the prognostic marker for the adjuvant chemotherapy of
      primary colorectal carcinoma. METHODS: Primary colorectal cancer tissue from 24
      patients was investigated to evaluate the relationship between the mRNA
      expression level of several 5-fluorouracil (5-FU)-related metabolic enzymes
      (thymidylate synthase, TS; dihydropyrimidine dehydrogenase, DPD; and thymidine
      phosphorylase, TP) and chemosensitivity to two different 5-FU doses and duration
      (1: 5-FU concentration 1.0 microg/mL (7.68 microM), 24 h exposure and 2: 5-FU
      concentration 0.3 microg/mL (2.30 microM), 144 h exposure). Chemosensitivity and
      mRNA expression levels were measured using collagen gel droplet embedded culture
      drug sensitivity tests and real-time quantitative reverse transcription
      polymerase chain reaction. Clinicopathological features and chemosensitivity were
      also compared. RESULTS: The TS mRNA expression level was significantly higher in
      the 5-FU resistant group (T/C > 60%) compared with the 5-FU sensitive group (T/C
      < 60%) in both 5-FU regimens (1: 5.03 +/- 0.92 vs. 1.58 +/- 0.76, p < 0.01, 2:
      4.88 +/- 0.91 vs. 0.96 +/- 0.20, p < 0.001). The group with the higher TS mRNA
      expression level (>3.83, the average) were more resistant to both 5-FU regimens
      than those with lower TS mRNA (<3.83) (1: T/C = 80 vs. 66%, p = 0.11, 2: T/C = 89
      vs. 64%, p < 0.005). The TS mRNA expression level inversely correlated with the
      sensitivity to the latter 5-FU regimen (R = 0.577, p < 0.01). There were no
      relationships between chemosensitivity to 5-FU and the mRNA expression level of
      DPD and TP and clinicopathological factors. CONCLUSIONS: The TS mRNA expression
      level might be a good marker of chemosensitivity to 5-FU in primary colorectal
      cancer, especially the sensitivity to low dose 5-FU with a long duration.

PMID- 17520255
TI  - A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate
      synthase inhibitor in combination with oxaliplatin in patients with advanced
      colorectal cancer.
AB  - PURPOSE: OSI-7904L is a liposomal formulation of a potent thymidylate synthase
      (TS) inhibitor. This phase I study evaluated the safety, tolerability and
      pharmacokinetics (PK) of OSI-7904L administered in combination with oxaliplatin
      every 21 days in patients with advanced colorectal carcinoma. METHOD: A 3+3 study
      design was utilized at predefined dose levels. Polymorphisms in the TS enhancer
      region and XPD enzyme were investigated as potential predictors of efficacy and
      toxicity. RESULTS: Fourteen patients received 76 cycles of treatment. At the
      highest dose level (OSI-7904L 9 mg/m(2), oxaliplatin 130 mg/m(2)) investigated,
      one of nine patients experienced dose-limiting toxicity of grade 3 oral mucositis
      with cycle 1 and five further patients required dose reductions. The toxicity
      profile of stomatitis, diarrhea, nausea, fatigue, sensory neuropathy and skin
      rash was consistent with that expected for a TS inhibitor/oxaliplatin combination
      regimen. PK analysis showed high interpatient variability with no detectable
      interaction between OSI-7904L and oxaliplatin. Partial radiological responses
      were documented in two patients. CONCLUSIONS: The recommended regimen for further
      investigation is OSI-7904L 9 mg/m(2) and oxaliplatin 130 mg/m(2).

PMID- 17520256
TI  - Oligo-microarray analysis reveals the role of cyclophilin A in drug resistance.
AB  - Cyclophilin A (CYPA) belongs to peptidyl prolyl isomerases (PPIases), which
      catalyze the cis/trans isomerization of prolyl peptide bonds in cellular
      communication. CYPA has been implicated in several pathological processes,
      including cancer, inflammatory diseases, and HIV-1 infection. Up-regulation of
      CYPA has been found to be a common phenomenon in several tumor types, including
      in hepatocellular carcinoma (HCC). However, the role of CYPA in tumor cells
      remains unknown. We generated a stable SK-Hep1 cell line and studied the CYPA
      regulated genes at the transcriptome level. The microarray results reveal that
      CYPA can up-regulate the expression of many cytokine and drug resistance related
      genes. Furthermore, we showed that the elevated CYPA expression contributes to
      drug resistance. We postulate that the over-expression of CYPA in tumors may play
      a role in clinical resistance to chemotherapy.

PMID- 17520257
TI  - Glut-1 as a therapeutic target: increased chemoresistance and HIF-1-independent
      link with cell turnover is revealed through COMPARE analysis and metabolomic
      studies.
AB  - The facilitative glucose transporter Glut-1 is overexpressed and confers poor
      prognosis in a wide range of solid tumours. The peri-necrotic pattern of
      expression often seen in human tumour samples is linked with its transcriptional
      control in hypoxic conditions by hypoxia-inducible factor HIF-1 or through a
      reduced rate of oxidative phosphorylation. Hypoxia-regulated genes offer promise
      as novel therapeutic targets as a means of preventing the proliferation and
      eventual metastatic spread of tissue originating from residual chemically and
      radio resistant hypoxic cells that have survived treatment. Inhibiting the
      expression or functionality of Glut-1 may be a way of specifically targeting
      hypoxic cells within the tumour that depend upon a high rate of glucose uptake
      for anaerobic glycolysis. We used an array of formalin-fixed, paraffin-embedded
      samples of the NCI-60 panel of cell lines to carry out immunohistochemical
      detection of Glut-1 and to select possible candidate lead compounds by COMPARE
      analysis with agents from the NCI diversity screen, which may work via inhibition
      of Glut-1 or Glut-1-dependent processes. "Positive" COMPARE hits were mostly
      conjugated Pseudomonas toxins binding the epidermal growth factor receptor
      (EGFR). However, correlations with standard anticancer agents were virtually all
      negative, indicating a link between Glut-1 and chemoresistance. MTT proliferation
      assays carried out using stable, Glut-1 overexpressing cell lines generated from
      the bladder EJ138, human fibrosarcoma HT 1080 and the hepatoma wild type Hepa and
      HIF-1B-deficient c4 tumour cell lines revealed a cell line-dependent increase in
      chemoresistance to dacarbazine, vincristine and the bioreductive agent EO9 in
      Glut-1 overexpressing EJ138 relative to WT and empty vector controls. Metabolomic
      analysis ((31)P-MRS and (1)H MRS) carried out using cell lysates and xenografts
      generated from Glut-1 overexpressing Hepa and c4 cell lines showed higher glucose
      levels in Glut-1 overxpressing c4 relative to parental tumour extracts occurred
      in the absence of an increase in lactate levels, which were in turn significantly
      higher in the Glut-1 overexpressing Hepa xenografts. This implies that Glut-1
      over-expression without a co-ordinate increase in HIF-1-regulated glycolytic
      enzymes increases glucose uptake but not the rate of glycolysis. Glut-1
      overexpressing xenografts also showed higher levels of phosphodiester (PDE),
      which relates to the metabolite turnover of phospholipids and is involved in
      membrane lipid degradation, indicating a mechanism by which Glut-1 may increase
      cell turnover.

PMID- 17520258
TI  - Pulmonary veno-occlusive disease as a primary cause of pulmonary hypertension in
      a patient with mixed connective tissue disease.
AB  - Mixed connective tissue disease (MCTD) is a systemic disease seen in a group of
      patients with overlapping clinical features of lupus, scleroderma, polymyositis,
      and rheumatoid arthritis. A defining feature of MCTD is the presence of
      antibodies against the U1-ribonucleoprotein (U1-RNP) complex. Pulmonary
      hypertension is the major cause of death in MCTD. We report an autopsy case of
      MCTD with pulmonary hypertension. The U1-RNP antibody of this patient was 171.9 U
      (normal < 25.0 U). The immediate cause of death was attributed to acute pulmonary
      embolism at left lower lobe. A severe vasculopathy characterized by fibrotic
      occlusion of small veins and venules, associated with prominent capillary
      congestion, was consistent with pulmonary veno-occlusive disease (PVOD). This is
      the first case reported in which PVOD is the primary cause of pulmonary
      hypertension in MCTD.

PMID- 17520259
TI  - Refractory retinal vasculitis due to sarcoidosis successfully treated with
      infliximab.
AB  - Sarcoidosis is a chronic disease of unknown etiology characterized by
      granulomatous infiltration of several organs. Up to two- thirds of patients
      develop ocular inflammation eventually leading to significant visual loss.
      Treatment includes corticosteroids and immunosuppressive agents, but refractory
      cases do occur. In this report, the authors describe two patients with multi
      systemic sarcoidosis and refractory retinal vasculitis who experienced an
      excellent response to infliximab. This report emphasizes the importance of TNF
      alpha in the pathophysiology of this disease and warrants further studies with
      anti-TNF therapy in patients with refractory ocular sarcoidosis.

PMID- 17520260
TI  - Effects of mud-bath treatment on fibromyalgia patients: a randomized clinical
      trial.
AB  - The efficacy of balneotherapy in fibromyalgia syndrome (FS) has been well
      demonstrated, while controlled studies using mud packs are lacking. We performed
      a randomized clinical trial to evaluate the effects and the tolerability of mud
      bath treatment in FS patients, who are poor responders to pharmacological
      therapy. Eighty patients with primary FS, according to ACR criteria, were
      randomly allocated to two groups: 40 were submitted to a cycle of 12 mud packs
      and thermal baths, and 40 were considered as controls. At baseline, after thermal
      treatment and after 16 weeks, patients were evaluated by FIQ, tender points
      count, VAS for "minor" symptoms, AIMS1 and HAQ. Control patients were assessed at
      the same time periods. A significant improvement of all evaluation parameters
      after mud-bath therapy and after 16 weeks was observed. Mud packs were well
      tolerated and no drop-outs were recorded. Our results suggest the efficacy and
      the tolerability of mud-bath treatment in primary FS.

PMID- 17520261
TI  - Modulation rate transfer functions in bottlenose dolphins (Tursiops truncatus)
      with normal hearing and high-frequency hearing loss.
AB  - Envelope following responses were measured in two bottlenose dolphins in response
      to sinusoidal amplitude modulated tones with carrier frequencies from 20 to 60
      kHz and modulation rates from 100 to 5,000 Hz. One subject had elevated hearing
      thresholds at higher frequencies, with threshold differences between subjects
      varying from +/-4 dB at 20 and 30 kHz to +40 dB at 50 and 60 kHz. At each carrier
      frequency, evoked response amplitudes and phase angles were plotted with respect
      to modulation frequency to construct modulation rate transfer functions. Results
      showed that both subjects could follow the stimulus envelope components up to at
      least 2,000 Hz, regardless of carrier frequency. There were no substantial
      differences in modulation rate transfer functions for the two subjects suggesting
      that reductions in hearing sensitivity did not result in reduced temporal
      processing ability. In contrast to earlier studies, phase data showed group
      delays of approximately 3.5 ms across the tested frequency range, implying
      generation site(s) within the brainstem rather than the periphery at modulation
      rates from 100 to 1,600 Hz. This discrepancy is believed to be the result of
      undersampling of the modulation rate during previous phase measurements.

PMID- 17520262
TI  - Acoustical expression of arousal in conflict situations in tree shrews (Tupaia
      belangeri).
AB  - Empirical research on human and non-human primates suggests that communication
      sounds express the intensity of an emotional state of a signaller. In the present
      study, we have examined communication sounds during induced social interactions
      of a monogamous mammal, the tree shrew. To signal their unwillingness to mate,
      female tree shrews show defensive threat displays towards unfamiliar males
      paralleled by acoustically variable squeaks. We assumed that the distance between
      interacting partners as well as the behavior of the male towards the female
      indicates the intensity of perceived social threat and thereby the arousal state
      of a female. To explore this hypothesis we analyzed dynamic changes in
      communication sounds uttered during induced social interactions between a female
      and an unfamiliar male. Detailed videographic and sound analyzes revealed that
      the arousal state predicted variations in communication sound structure reliably.
      Both, a decrease of distance and a male approaching the female led to an increase
      in fundamental frequency and repetition rate of syllables. These findings support
      comparable results in human and non-human primates and suggest that common coding
      rules in communication sounds govern acoustic conflict regulation in mammals.

PMID- 17520263
TI  - Steroid correlates of multiple color traits in the spiny lizard, Sceloporus
      pyrocephalus.
AB  - Conspicuous coloration in females is less well studied compared to that in males.
      Adult female Mexican boulder spiny lizards (Sceloporus pyrocephalus) have
      conspicuously colored throat, or gular, regions, ranging from red to yellow,
      while adult males only weakly express such color in their gular region. Both
      sexes have dark blue-black gular stripes and venter stripes. Understanding
      proximate mechanisms underlying trait expression can aid in understanding trait
      function. To characterize the proximate mechanisms potentially influencing color
      variation among field-captured male and female S. pyrocephalus, we quantified
      three aspects of color (hue, saturation, brightness) for three body locations
      (gular region, gular stripes, venter stripes) and then assessed how color was
      related to reproductive state and concentrations of the plasma steroid hormones
      testosterone (T) and corticosterone (CORT) in males and T, CORT, and 17-beta
      estradiol (E(2)) in females. Testes volume was not related to variation in color
      or in hormones, perhaps because most males were in peak reproductive condition.
      Large vitellogenic follicles as opposed to oviductal eggs were associated with
      higher E(2) in females. Males with more dull gular stripes and females with dull
      venter stripes had significantly higher CORT. Females with red gular regions and
      pale grey gular stripes had higher T and E(2) concentrations compared to females
      with a more yellow gular region and darker gular stripes. Thus, gular region
      color in females could communicate reproductive state; dull gular stripes in
      males and dull venter stripes in females could communicate stress status.

PMID- 17520264
TI  - The effect of neo-rectal wall properties on functional outcome after colonic J
      pouch-anal anastomosis.
AB  - BACKGROUND/AIMS: It has been suggested that normal function of both anal
      sphincters is essential for a good functional outcome after colonic J-pouch-anal
      anastomosis (CPAA). However, CPAA patients may have impaired continence despite
      adequate sphincter function. The present study was designed to identify those
      factors, which contribute to the functional outcome after a handsewn CPAA.
      MATERIALS AND METHODS: Forty patients were studied before and 1 year after pouch
      surgery. Faecal continence was evaluated using the Rockwood faecal incontinence
      severity index (RFISI). At both occasions, maximum anal resting pressure (MARP)
      and maximum anal squeeze pressure (MASP) were recorded. In addition, sensory
      perception threshold-volumes (SPT-V) and compliance were assessed using an
      'infinitely' compliant polyethylene bag connected to an electronic barostat
      assembly. RESULTS: The median RFISI score 1 year after surgery was higher than
      the median RFISI score before surgery (13 vs 7 (p < 0.01). The median MARP
      dropped significantly (p < 0.01) whereas the median MASP remained unaffected. The
      mean compliance, calculated at three different sensation levels, and the pouch
      sensory perception threshold-volumes (PSPT-V) were lower than those of the
      original rectum (p < 0.05). The reduction of MARP showed no correlation with the
      post-operative change in RFISI scores. Low PC and low PSPT-V were associated with
      higher RFISI scores. CONCLUSION: Low pouch compliance and low SPT-V adversely
      affect functional outcome after a handsewn colonic J-pouch-anal anastomosis.

PMID- 17520265
TI  - Surgical treatment in cocaine body packers and body pushers.
AB  - OBJECTIVE: Body packers smuggle cocaine by swallowing containers filled with the
      drugs, whilst body pushers conceal the containers in the rectum or vagina. In a
      collaborative effort between the Department of General Surgery, two major
      airports and Poisons Centre, we performed a retrospective study to develop an
      algorithm for the treatment of ruptured cocaine-filled containers. MATERIALS AND
      METHODS: The data of all cocaine body packers and body pushers who were
      identified at the airports of Frankfurt and Paris from 1985 to 2002 were
      evaluated concerning incidence, demographics and surgical aspects. RESULTS: From
      1985 to 2002, 312 body pushers and 4,660 body packers were identified. The sex
      ratio was 1:1. Sixty-four "mules" (1.4%) developed life-threatening symptoms of
      cocaine overdose after the rupture of a container. In 20 patients, an emergency
      laparotomy was performed and the containers were removed; all of these patients
      survived. Forty-four body packers died before surgical treatment could be
      performed. Only one body pusher required medical attention. CONCLUSION: Cocaine
      overdose can be life-threatening. If the cause is the rupture of a container in a
      body packer, the only possible treatment is immediate laparotomy for the removal
      of the container.

PMID- 17520267
TI  - Efficacy of the barbecue manoeuvre in benign paroxysmal vertigo of the horizontal
      canal.
AB  - Five to ten percent of benign paroxysmal positional vertigo are caused by the
      horizontal semi-circular variant (h-BPPV). In this study, we reviewed the
      efficacy of the Barbecue repositioning manoeuvre in h-BPPV, and we assessed the
      possible effect of different factors on the outcome. Barbecue manoeuvre consists
      in turning the supine patient around his longitudinal axis toward the unaffected
      side until 360 degrees are accomplished. After every 90 degrees step the patient
      is maintained in the new position for 30 s. We reviewed 46 patients with h-BPPV,
      treated by barbecue rotation from 2003 to 2005. After the first Barbecue
      manoeuvre, the patients were followed-up at intervals of approximately 1 week and
      the rotation was repeated if h-BPPV persisted (up to three rotations). Factors
      assessed were age, gender, duration of symptoms before treatment and type of h
      BPPV (canalolithiasis vs. cupulolithiasis). Fisher's exact test was used for the
      analysis. RESULTS: 85% of patients (39/46) were cured after a maximum of 3
      rotations. 74% (34/46) were cured after the first manoeuvre and 80% (37/46) after
      the second one. None of the evaluated factors did significantly affect the
      efficacy (P > 0.05). The Barbecue manoeuvre is an efficient treatment of h-BPPV
      demonstrating 85% cure rate after a maximum of three sessions. 74% of the
      patients are healed after one manoeuvre. The efficacy is not affected by the
      evaluated factors.

PMID- 17520266
TI  - Substance P induces intestinal wound healing via fibroblasts--evidence for a TGF
      beta-dependent effect.
AB  - BACKGROUND: Substance P (SP) and calcitonin gene-related peptide (CGRP) are
      neurotransmitters of the afferent sensory nervous system. In experimental models
      of colitis in rats and rabbits, a protective role of SP and CGRP on the
      intestinal mucosa was presumed. In part, mucosal protection depends on a SP
      mediated and CGRP-mediated modulation of mucosal blood flow after injury. We
      thought to explore whether there is a fibroblast-mediated effect of SP and CGRP
      on epithelial cell restitution in vitro. MATERIALS AND METHODS: Rat kidney
      fibroblast (NRK-49F) cell lines were exposed to CGRP or SP in various
      concentrations. After incubation, the cell culture supernatants were taken from
      the fibroblast cultures and were directly applied to IEC-18 or Caco-2 monolayers,
      which had been wounded with a razor blade 24 h before the experiments. Epithelial
      cell migration was assessed by counting cells across the wound edge. Epithelial
      cell proliferation was assessed using the 3-[4, 5-dimethylthiazol-2-yl]-2, 5
      diphenyl-tetrazolium bromide (MTT) test. RESULTS: SP significantly induced
      epithelial cell migration and inhibited epithelial cell proliferation via
      stimulation of fibroblasts when supernatants were directly applied to epithelial
      cells in vitro. The effects on epithelial cell migration were abolished after
      neutralising anti-transforming growth factor-beta (TGF-beta) was added to the
      cell cultures. CGRP had no effect on epithelial cells via stimulation of
      fibroblasts. Neither CGRP nor SP had any effect on epithelial cell migration or
      proliferation when directly applied to epithelial cells. CONCLUSION: SP modulates
      epithelial cell restitution in vitro mediated by fibroblasts. The epithelial cell
      migration depends on a TGF-beta release from SP-stimulated fibroblasts. This
      observation underlines an important role for the sensory nervous system in
      mucosal defence and repair and in keeping mucosal homeostasis. Modulation of SP
      may be potentially useful for the treatment of various intestinal disorders
      characterised by injury and ineffective repair of the intestinal mucosa.

PMID- 17520268
TI  - Thyroid hormone receptor alpha1 is a critical regulator for the expression of ion
      channels during final differentiation of outer hair cells.
AB  - Cochlear outer hair cells (OHCs) terminally differentiate prior to the onset of
      hearing. During this time period, thyroid hormone (TH) dramatically influences
      inner ear development. It has been shown recently that TH enhances the expression
      of the motor protein prestin via liganded TH receptor beta (TRbeta) while in
      contrast the expression of the potassium channel KCNQ4 is repressed by unliganded
      TRalpha1. These different mechanisms of TH regulation by TRalpha1 or TRbeta
      prompted us to analyse other ion channels that are required for the final
      differentiation of OHCs. We analysed the onset of expression of the Ca(2+)
      channel Ca(V)1.3, and the K(+) channels SK2 and BK and correlated the results
      with the regulation via TRalpha1 or TRbeta. The data support the hypothesis that
      proteins expressed in rodents prior to or briefly after birth like Ca(V)1.3 and
      prestin are either independent of TH (e.g. Ca(V)1.3) or enhanced through TRbeta
      (e.g. prestin). In contrast, proteins expressed in rodents later than P6 like
      KCNQ4 ( approximately P6), SK2 ( approximately P9) and BK ( approximately P11)
      are repressed through TRalpha1. We hypothesise that the precise regulation of
      expression of the latter genes requires a critical local TH level to overcome the
      TRalpha1 repression.

PMID- 17520269
TI  - Expression and histochemical localization of ciliary neurotrophic factor in
      cultured adult rat dorsal root ganglion neurons.
AB  - Ciliary neurotrophic factor (CNTF) is abundantly expressed in Schwann cells in
      adult mammalian peripheral nerves, but not in neurons. After peripheral nerve
      injury, CNTF released from disrupted Schwann cells is likely to promote neuronal
      survival and axonal regeneration. In the present study, we examined the
      expression and histochemical localization of CNTF in adult rat DRG in vivo and in
      vitro. In contrast to the restricted expression in Schwann cells in vivo, we
      observed abundant CNTF mRNA and protein expression in DRG neurons after 3 h, 2,
      7, and 15 days in dissociated cell culture. At later stages (7 and 15 days) of
      culture, CNTF immunoreactivity was detected in both neuronal cell bodies and
      regenerating neurites. These results suggest that CNTF is synthesized and
      transported to neurites in cultured DRG neurons. Since we failed to observe CNTF
      immunoreactivity in DRG neurons in explant culture, disruption of cell-cell
      interactions, rather than the culture itself, may be an inducible factor for
      localization of CNTF in the neurons.

PMID- 17520270
TI  - On the inappropriateness of stepwise regression analysis for model building and
      testing.

PMID- 17520271
TI  - Changes in blood flow in a conduit artery and superficial vein of the upper arm
      during passive heating in humans.
AB  - The purposes of this study were (1) to evaluate changes in blood flow in the
      brachial artery and basilic vein of the upper arm with a rise in internal
      temperature during passive heating; and (2) to investigate the contributions of
      blood velocity and anteroposterior vessel diameter to these blood flow changes.
      Ten subjects rested in the supine position between a pair of tube-lined sheets.
      Thermoneutral water was circulated through the tubes to keep a mean skin
      temperature (Tsk) of 34-35 degrees C, and then hot water was circulated to
      maintain Tsk of 37-38 degrees C. The blood velocity and diameter in the brachial
      artery and basilic vein were continuously monitored by Doppler ultrasound
      technique and used to calculate blood flow. Blood flow in the brachial artery and
      basilic vein increased linearly as the oral temperature (T(or)) rose by < or =0.6
      degrees C. The magnitude of the change in blood flow did not differ significantly
      between the two vessels. In addition, plots of DeltaT(or) versus blood flow
      yielded slopes that did not differ significantly between the brachial artery and
      the basilic vein. As T (or) increased, blood velocity, but not diameter, also
      increased. In conclusion, blood flow in the brachial artery and the basilic vein
      increased linearly as the internal temperature variable T (or) increased < or
      =0.6 degrees C. In both vessels, the passive heating-induced increases in blood
      flow resulted primarily from a change in blood velocity, rather than from a
      change in diameter.

PMID- 17520272
TI  - Plasma lactate accumulation is reduced during incremental exercise in untrained
      women compared with untrained men.
AB  - The lactate threshold (LT) is commonly reported as not different between sexes,
      yet lower blood lactate concentrations have been reported in women during
      submaximal exercise. The purpose of the present study was to measure the changes
      in plasma lactate concentration [La(-1)] in men and women during incremental
      cycle ergometer exercise using the same protocol and compare the data using
      several different methods of analysis. A group of untrained men (n = 21) and
      women (n = 22) were studied and venous blood drawn at regular intervals during
      and after exercise for assay of plasma [La(-1)]. Plasma [La(-1)] increased during
      exercise in both sexes, reaching higher values in men, both at exhaustion (men
      8.6 +/- 2.3 mmol l(-1); women 6.2 +/- 2.3 mmol l(-1); P = 0.01) and post-exercise
      (men 11.8 +/- 2.1 mmol l(-1); women 10.2 +/- 2.4 mmol l(-1); P = 0.03).
      Logarithmic transformation of the data yielded LT values that were not different
      between sexes (men 44.2 +/- 12.9; women 50.2 +/- 12.6; %VO2peak; P = 0.45), yet
      both the 2 and 4 mmol l(-1) fixed concentration LT occurred at lower relative
      intensities in men (2 mmol l(-1): men 50.9 +/- 12.9; women 66.9 +/- 11.1;
      %VO2peak; P = 0.01). 4 mmol l(-1): men 75.7 +/- 11.0; women 90.6 +/- 9.2;
      VO2peak; P = 0.01). However, when the plasma [La(-1)] was examined in both sexes
      throughout exercise, using a single exponential function, plasma [La(-1)] was
      significantly lower in women (P < 0.05) at all relative intensities between 30
      and 100%VO2peak. While the basis of this sex difference is unknown, reduced
      plasma [La(-1)] during submaximal exercise in women may offset to some degree the
      endurance performance disadvantage of their lower VO2peak.

PMID- 17520273
TI  - Animal navigation: the difficulty of moving in a straight line.
AB  - In principle, there are two strategies for navigating a straight course. One is
      to use an external directional reference and continually reorienting with
      reference to it, while the other is to infer body rotations from internal sensory
      information only. We show here that, while the first strategy will enable an
      animal or mobile agent to move arbitrarily far away from its starting point, the
      second strategy will not do so, even after an infinite number of steps. Thus, an
      external directional reference-some form of compass-is indispensable for ensuring
      progress away from home. This limitation must place significant constraints on
      the evolution of biological navigation systems. Some specific examples are
      discussed. An important corollary arising from the analysis of compassless
      navigation is that the maximum expected displacement represents a robust measure
      of the straightness of a path.

PMID- 17520274
TI  - Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5
      kinases.
AB  - Phosphatidylinositol (4,5)-bisphosphate (PIP(2)) is an important lipid mediator
      that has multiple regulatory functions. There is now increasing evidence that the
      phosphatidylinositol 4-phosphate 5 kinases (PIP5Ks), which synthesize PIP(2), are
      regulated spatially and temporally and that they have isoform-specific functions
      and regulations. This review will summarize the highlights of recent developments
      in understanding how the three major PIP5K isoforms regulate the actin
      cytoskeleton and other important cellular processes.

PMID- 17520275
TI  - Antagonism of stromal cell-derived factor-1alpha reduces infarct size and
      improves ventricular function after myocardial infarction.
AB  - To examine the biological impact of locally expressed stromal cell-derived factor
      1alpha (SDF-1alpha) during the acute phase of remodeling after myocardial
      infarction (MI), rats were treated with the selective CXCR4 receptor antagonist
      AMD3100 (1 mg/kg; given 24 h post-MI and continued for 6 days). In 1-week post-MI
      rats, intense SDF-1 immunoreactivity was detected in scar-residing vessels, and
      SDF-1alpha messenger ribonucleic acid (mRNA) levels were significantly greater in
      the infarct region compared to the noninfarcted left ventricle (NILV). AMD3100
      treatment of post-MI rats reduced infarct size, improved systolic function, and
      partially suppressed the increased expression of atrial natriuretic peptide mRNA
      in the NILV. The latter finding indirectly suggests that SDF-1alpha may have
      contributed to the hypertrophic response of the NILV. SDF-1alpha treatment of
      neonatal rat ventricular myocytes (NNVMs) failed to promote protein synthesis.
      However, in hypertrophied NNVMs, SDF-1alpha treatment further augmented (3)H
      leucine uptake, and AMD3100 selectively inhibited the increase in protein
      synthesis. Collectively, these data support the existence of an SDF-1alpha
      gradient in the damaged rat myocardium increasing toward the infarct region and
      highlight the novel observation that AMD3100 antagonism of the SDF-1alpha/CXCR4
      axis reduced scar expansion and improved contractility. In vitro data further
      suggest that SDF-1alpha may have contributed to the hypertrophic response of the
      NILV.

PMID- 17520277
TI  - Production and characterization of arboreous and fertile Solanum melongena +
      Solanum marginatum somatic hybrid plants.
AB  - In crop plants the shift from being annuals to perennials may allow future
      agricultural systems requiring less energy inputs. The practicability of this was
      tested for Solanum melongena. Leaf protoplasts of S. melongena (2n = 2x = 24) and
      one of the related arborescent species Solanum marginatum (2n = 2x = 24) were
      electrofused and fertile somatic hybrids with arborescent habit regenerated. The
      magnetic cell sorter (MACS) technique was used for the selection of
      heterokaryons. The hybrid nature of 18 regenerated plants was assessed on the
      banding patterns generated by inter-simple sequence repeat PCR. When taken to
      maturity in the greenhouse, hybrids grew more vigorously compared to the parental
      species. Their morphological traits were intermediate between those of S.
      melongena and S. marginatum. Hybrids flowered and produced an average of 85%
      stainable viable pollen and fertile fruits. The somatic hybrids were maintained
      in the greenhouse for more than 3 years and continued to produce flowers
      developing into two types of fruits with plentiful seeds. Fruits were either
      striated green containing non-germinable seeds or yellow with fully germinable
      seeds. Their S(1) progenies showed common features with S(0) hybrids, including
      fertility and arborescent habit. Cytologically, somatic hybrids exhibited the
      expected chromosome number of 2n = 4x = 48, while chromosome pairing during
      microsporogenesis was associated with a low frequency of intergenomic pairing. It
      is concluded that an arborescent perennial species has been obtained by somatic
      hybridization. The usefulness of this species per se or in eggplant breeding will
      depend not only on the transmission of the arborescent habit to cultivated
      eggplant varieties, but also on the variability that should be created from
      backcrossing the S. melongena + S. marginatum hybrids to S. melongena.

PMID- 17520276
TI  - Phosphoinositide-mediated gating of inwardly rectifying K(+) channels.
AB  - Phosphoinositides, such as phosphatidylinositol-bisphosphate (PIP(2)), control
      the activity of many ion channels in yet undefined ways. Inwardly, rectifying
      potassium (Kir) channels were the first shown to be dependent on direct
      interactions with phosphoinositides. Alterations in channel-PIP(2) interactions
      affect Kir single-channel gating behavior. Aberrations in channel-PIP(2)
      interactions can lead to human disease. As the activity of all Kir channels
      depends on their interactions with phosphoinositides, future research will aim to
      understand the molecular events that occur from phosphoinositide binding to
      channel gating. The determination of atomic resolution structures for several
      mammalian and bacterial Kir channels provides great promise towards this goal. We
      have mapped onto the three-dimensional channel structure the position of basic
      residues identified through mutagenesis studies that contribute to the
      sensitivity of a Kir channel to PIP(2). The localization of these putative PIP(2)
      interacting residues relative to the channel's permeation pathway has given rise
      to a testable model, which could account for channel activation by PIP(2).

PMID- 17520278
TI  - Meristem maintenance and compound-leaf patterning utilize common genetic
      mechanisms in tomato.
AB  - Balancing shoot apical meristem (SAM) maintenance and organ formation from its
      flanks is essential for proper plant growth and development and for the
      flexibility of organ production in response to internal and external cues. Leaves
      are formed at the SAM flanks and display a wide variability in size and form.
      Tomato (Solanum lycopersicum) leaves are compound with lobed margins. We
      exploited 18 recessive tomato mutants, representing four distinct phenotypic
      classes and six complementation groups, to track the genetic mechanisms involved
      in meristem function and compound-leaf patterning in tomato. In goblet (gob)
      mutants, the SAM terminates following cotyledon production, but occasionally
      partially recovers and produces simple leaves. expelled shoot (exp) meristems
      terminate after the production of several leaves, and these leaves show a reduced
      level of compoundness. short pedicel (spd) mutants are bushy, with impaired
      meristem structure, compact inflorescences, short pedicels and less compound
      leaves. In multi drop (mud) mutants, the leaves are more compound and the SAM
      tends to divide into two active meristems after the production of a few leaves.
      The range of leaf-compoundness phenotypes observed in these mutants suggests that
      compound-leaf patterning involves an array of genetic factors, which act
      successively to elaborate leaf shape. Furthermore, the results indicate that
      similar mechanisms underlie SAM activity and compound-leaf patterning in tomato.

PMID- 17520279
TI  - Patterns of asexual reproduction in Nannochloris bacillaris and Marvania geminata
      (Chlorophyta, Trebouxiophyceae).
AB  - Non-flagellated vegetative green algae of the Trebouxiophyceae propagate mainly
      by autosporulation. In this manner, the mother cell wall is shed following
      division of the protoplast in each round of cell division. Binary fission type
      Nannochloris and budding type Marvania are also included in the Trebouxiophyceae.
      Phylogenetic trees based on the actin sequences of Trebouxiophyceae members
      revealed that the binary fission type Nannochloris bacillaris and the budding
      type Marvania geminata are closely related in a distal monophyletic group. Our
      results suggest that autosporulation is the ancestral mode of cell division in
      Trebouxiophyceae. To elucidate how non-autosporulative mechanisms such as binary
      fission and budding evolved, we focused on the cleavage of the mother cell wall.
      Cell wall development was analyzed using a cell wall-specific fluorescent dye,
      Fluostain I. Exfoliation of the mother cell wall was not observed in either N.
      bacillaris or M. geminata. We then compared the two algae by transmission
      electron microscopy with rapid freeze fixation and freeze substitution; in both
      algae, the mother cell wall was cleaved at the site of cell division, but
      remained adhered to the daughter cell wall. In N. bacillaris, the cleaved mother
      cell wall gradually degenerated and was not observed in the next cell cycle. In
      contrast, M. geminata daughter cells entered the growth phase of the next cell
      cycle bearing the mother and grandmother cell walls, causing the uncovered
      portion of the plane of division to bulge outward. Such a delay in the
      degeneration and shedding of the mother cell wall probably led to the development
      of binary fission and budding.

PMID- 17520280
TI  - Rhizome transition to storage organ is under phytochrome control in lotus
      (Nelumbo nucifera).
AB  - We examined photoperiodic response of lotus (Nelumbo nucifera) rhizome
      morphogenesis (its transition to a storage organ) by using seed-derived plants.
      Rhizome enlargement (increase in girth) was brought about under 8, 10 and 12 h
      photoperiods, whereas the rhizomes elongated under 13 and 14 h photoperiods.
      Rhizomes elongated under 14 h light regimes supplied as 8 h of natural light plus
      6 h supplemental hours of white, yellow or red light, but similar treatments with
      supplemental blue, green or far red light, caused enlargement in girth of the
      rhizomes. A 2 h interruption of the night with white, yellow or red light, in
      plants entrained to 8 h photoperiod brought rhizome elongation, whereas 2 h-blue,
      green or far red light night breaks still resulted in rhizome increase in girth.
      The inhibitory effect of a red (R) light night break on rhizome increase in girth
      was reversed by a far-red (FR) light given immediately afterwards. Irradiation
      with R/FR/R inhibited the rhizome increase in girth. FR light irradiation
      following R/FR/R irradiation cancelled the effect of the last R light
      irradiation. It was demonstrated that the critical photoperiod for rhizome
      transition to storage organ is between 12 and 13 h photoperiod. It was also
      evident that the optimal light quality range for interruption of dark period
      (night break) is between yellow and red light and that a R/FR reversible reaction
      is observed. From these results, we propose that phytochrome plays an important
      role in photoperiodic response of rhizome increase in girth in lotus. This is the
      first report on phytochrome-dependent morphogenesis of storage organs in
      rhizomous plants.

PMID- 17520281
TI  - Both the adaxial and abaxial epidermal layers of the rose petal emit volatile
      scent compounds.
AB  - The localization and timing of production and emission of scent was studied in
      different Rosa x hybrida cultivars, focusing on three particular topics. First,
      it was found that petals represent the major source of scent in R. x hybrida. In
      heavily scented cultivars, the spectrum and levels of volatiles emitted by the
      flower broadly correlated with the spectrum and levels of volatiles contained
      within the petal, throughout petal development. Secondly, analysis of rose
      cultivars that lacked a detectable scent indicated that the absence of fragrance
      was due to a reduction in both the biosynthesis and emission of scent volatiles.
      A cytological study, conducted on scented and non-scented rose cultivars showed
      that no major difference was visible in the anatomy of the petals either at small
      magnification in optical sections or in ultrathin sections observed by TEM. In
      particular, the cuticle of epidermal cells was not thicker in scentless
      cultivars. Thirdly, using two different techniques, solid/liquid phase extraction
      and headspace collection of volatiles, we showed that in roses, both epidermal
      layers are capable of producing and emitting scent volatiles, despite the
      different morphologies of the cells of these two tissues. Moreover, OOMT, an
      enzyme involved in scent molecule biosynthesis was localized in both epidermal
      layers.

PMID- 17520282
TI  - Inhibition of hemagglutination activity of influenza A viruses by SP-A1 and SP-A2
      variants expressed in CHO cells.
AB  - Surfactant protein A (SP-A) inhibits hemagglutination (HA) activity and
      infectivity of influenza A viruses (IAV). As we have showed before in different
      assays, SP-A2 gene products are more active than SP-A1. Here, we hypothesized
      that SP-A1 and SP-A2 mammalian CHO-cell-expressed proteins also differentially
      modulate HA inhibition of IAV. We found that both SP-A1 and SP-A2 equally
      displayed alpha(2,3)-linked sialic acids, and had similar activity against a
      strain (PR-8) that preferentially binds to alpha(2,3)-linked sialic acids. Based
      on these findings, we speculate that in human lung SP-A1 and SP-A2 will not be
      different in their activity against IAV that preferably bind to alpha(2,3)-linked
      sialic acids (like avian strains).

PMID- 17520283
TI  - A case of systemic aplasia cutis congenita: a newly recognized syndrome?
AB  - Aplasia cutis congenita, congenital absence of a localized area of skin, usually
      on the vertex of the scalp, occurs as an isolated defect, or with one or more
      other congenital anomalies as part of a syndrome, sequence or association. To
      date, more than 500 cases have been reported. A more severe and extensive form,
      almost complete absence of skin and subcutaneous tissue, was reported by Park et
      al. in 1998 [J Med Genet 35:609-611]. Until now, no other such lethal case has
      been reported. Here, we report the second case of systemic aplasia cutis
      congenita. The female was born without any skin at all, and with hypoplastic
      lungs, syndactyly, skull defect, esophageal atresia, intestinal malrotation, and
      calcifications of the hepatic capsule, as well as with other anomalies. She died
      about 12 hours after birth probably due to dehydration. On microscopic
      examination, the external surface of the body showed complete absence of the
      epidermis. Muscle fibers were thin. There was no evidence of skin appendages. The
      present case gives strong support to the suggestion that systemic aplasia cutis
      congenita is a newly recognized syndrome. More cases will have to be reported and
      studied in order to understand the etiology and establish diagnostic criteria.
      Thus, it is our conclusion that systemic aplasia cutis congenita might be a newly
      recognized syndrome.

PMID- 17520284
TI  - The familial Mediterranean fever (MEFV) gene may be a modifier factor of
      inflammatory bowel disease in infancy.
AB  - Pediatric inflammatory bowel disease (IBD) usually manifests in childhood or
      adolescence, but a small number of cases present in infancy. Genetic factors are
      more important than environmental ones in the onset of pediatric IBD. We report
      here the concurrent manifestation of IBD and familial Mediterranean fever (FMF)
      in three infants (less than 6 months of age) in whom infantile ulcerative colitis
      (UC) was associated with the MEFV mutation. One patient required colectomy before
      the diagnosis of FMF, and in the other two patients, the UC could not be
      controlled until colchicine was added to the drug regimen. We suggest that the
      onset of UC in infants should prompt a search for MEFV mutations as this
      association may influence the management of the disease.

PMID- 17520285
TI  - Monozygous twins with a microdeletion syndrome involving BTK, DDP1, and two other
      genes; evidence of intact dendritic cell development and TLR responses.
AB  - We report for the first time monozygous twins with a microdeletion syndrome
      involving genes coding for Bruton's tyrosine kinase (Btk) and deafness-dystonia
      peptide 1 (DDP1), and two other genes. Apart from its essential role in B cell
      development, Btk is indicated to affect signaling mediated by toll like receptors
      (TLRs) and development of dendritic cells (DCs) but results are conflictive. The
      twins revealed normal numbers of plasmacytoid and myeloid DCs (pDCs and mDCs).
      Moreover, BTK null cells from these patients exhibited robust responses to TLR
      agonists, normal natural killer (NK) cell activity, and normal pDC functions.
      CONCLUSION: Our results do not indicate the essential role of Btk in TLR
      signaling and DC development.

PMID- 17520286
TI  - New experimental markers for early detection of high-risk prostate cancer: role
      of cell-cell adhesion and cell migration.
AB  - Today's treatment and diagnosis of prostate cancer still exhibit major
      limitations. The search for new and additional prognostic markers is therefore
      still an actual field of interest. Potential markers involved in numerous
      biological processes in the tumor cell have been investigated intensively. For
      therapeutic interventions it is important to distinguish between harmless and
      aggressive disease in an early stage. Therefore the subject of this review is
      limited to markers associated with those functional processes, which discriminate
      early stage aggressive, metastatic cancer from harmless disease. Important
      processes in this respect are: altered cell adhesion and cellular migration. E
      cadherin, N-cadherin, beta-catenin, integrins, focal adhesion kinase, connexins
      and matrix metalloproteinases all appear promising biological markers associated
      with the early stage metastatic process in prostate cancer. Here we discuss their
      potential to become valid biological markers based on literature data. Thus far,
      none of these markers proved to be a valid individual marker by itself due to
      prostate cancer heterogeneity and transient expression. Analyzing a combination
      of the potential markers discussed in this review is expected to be a better
      approach toward discriminating high- from low-risk tumors in an early stage of
      prostate cancer.

PMID- 17520287
TI  - The intestinal nematode Trichuris arvicolae affects the fecundity of its host,
      the common vole Microtus arvalis.
AB  - Parasites have detrimental effects on host fitness. Consequently, they play a
      major role for host population dynamics. In this study, we investigated
      experimentally the impact of the nematode Trichuris arvicolae on the reproduction
      of its host, the common vole Microtus arvalis. Wild common voles were trapped in
      east of France and reared in standardized conditions before being experimentally
      infected. Infection with Trichuris arvicolae did not affect host consumption of
      food or water. Parasitized females gave birth to slightly less pups (mean 3.36 +/
      0.38) than unparasitized females (mean 3.60 +/- 0.40). Controlling for natal
      litter size using analysis of covariance (ANCOVA), T. arvicolae infection had a
      significant effect on the individual mass at birth, with pups from parasitized
      females having significantly lower mass (2.11 g +/- 0.01) than pups from
      unparasitized females (2.20 g +/- 0.01). Other measures of host reproductive
      outputs (time to first reproduction, mass of pups at weaning, litter survival)
      were not affected by maternal parasite infection. We discuss how these changes in
      M. arvalis reproductive investments associated with T. arvicolae infection must
      now be investigated in the context of physiological trade-offs.

PMID- 17520288
TI  - Evaluation of mosquitocidal activity of essential oil and sesquiterpenes from
      leaves of Chloroxylon swietenia DC.
AB  - Growing awareness in using ecofriendly and biologically compatible
      phytoconstituents as natural insecticides and repellents for the safety of life
      and ecological balance led to conscientious efforts by scientists all over the
      world to search for alternative sources of plant derivatives for effective use as
      mosquitocides. Encouraged by this, the essential oil and the sesquiterpenes
      isolated from the leaves of Chloroxylon swietenia DC. were screened for
      mosquitocidal activity by fumigant toxicity against three mosquito species,
      Anopheles gambiae, Culex quinquefasciatus and Aedes aegypti. The essential oil
      had pronounced mosquitocidal activity with LD50 of 1.0, 1.2 and 1.7 x 10(-3)
      mg/cm(-3), respectively, for the three vector species. Furthermore, the major
      sesquiterpenes were tested at different doses, which again showed varying levels
      of toxicity. However, germacrene D performed better and proved to be the
      potential candidate with LD50 values of 1.8-2.8 x 10(-3) mg/cm(-3) followed by
      pregeijerene and geijerene. Nevertheless, the oil and the isolated compounds were
      particularly active against A. gambiae. The essential oil from the leaves was
      obtained by hydrodistillation, and the chemical composition was determined by GC
      and GC-MS. The main compounds identified were limonene, germacrene D, geijerene,
      pregeijerene, trans-beta-ocimene and methyl eugenol. The present study indicates
      that the oil and the isolated compounds of C. swietenia displayed remarkable
      mosquitocidal activity suggesting that the method could be extended for future
      field trials in various mosquito control programmes, and the results are compared
      with synthetic insecticides.

PMID- 17520289
TI  - Effect of cytokine treatment on the in vitro expression of the P. falciparum
      adhesion receptor chondroitin-4-sulphate on the surface of human choriocarcinoma
      (BeWo) cells.
AB  - BeWo human choriocarcinoma cells have recently been identified as an in vitro
      model of adhesion of Plasmodium falciparum-infected erythrocytes to the major
      placental receptor chondroitn-4-sulphate (CSA). In this study, we show that
      treatment of BeWo cells with tumour necrosis factor-alpha and/or interferon
      gamma, cytokines linked with pregnancy-associated malaria and poor pregnancy
      outcome, does not alter the expression of cell surface CSA. BeWo cells do not
      express the common P. falciparum adhesion receptor cluster of differentiation 36
      (CD36) on the cell surface, and this was unchanged after treatment with
      cytokines. These data demonstrate that in vitro cultured BeWo cells mimic the P.
      falciparum adhesion receptor expression profile of ex vivo placental
      cytotrophoblast cells.

PMID- 17520290
TI  - Helminth parasites of reptiles (Reptilia) in Romania.

PMID- 17520291
TI  - Identification and characterization of segregation distortion loci along
      chromosome 5B in tetraploid wheat.
AB  - Segregation distortion genes are widespread in plants and animals and function by
      their effect on competition among gametes for preferential fertilization. In this
      study, we evaluated the segregation distortion of molecular markers in multiple
      reciprocal backcross populations derived from unique cytogenetic stocks involving
      the durum cultivar Langdon (LDN) and wild emmer accessions that allowed us to
      study the effects of chromosome 5B in isolation. No segregation distortion of
      female gametes was observed, but three populations developed to analyze
      segregation of male gametes had genomic regions containing markers with skewed
      segregation ratios. One region of distortion was due to preferential transmission
      of LDN alleles over wild emmer alleles through male gametes. Another region
      required the presence of LDN 5B chromosomes in the female for preferential
      fertilization by male gametes harboring LDN alleles indicating that the
      corresponding genes in the female gametes can govern genes affecting segregation
      distortion of male gametes. A third region of distortion was the result of
      preferential transmission of wild emmer alleles over LDN alleles through male
      gametes. These results indicate the existence of different distorter/meiotic
      drive elements among different genotypes and show that distortion factors along
      wheat chromosome 5B differ in chromosomal location as well as underlying
      mechanisms.

PMID- 17520292
TI  - Chromosomal location and gene paucity of the male specific region on papaya Y
      chromosome.
AB  - Sex chromosomes in flowering plants evolved recently and many of them remain
      homomorphic, including those in papaya. We investigated the chromosomal location
      of papaya's small male specific region of the hermaphrodite Y (Yh) chromosome
      (MSY) and its genomic features. We conducted chromosome fluorescence in situ
      hybridization mapping of Yh-specific bacterial artificial chromosomes (BACs) and
      placed the MSY near the centromere of the papaya Y chromosome. Then we sequenced
      five MSY BACs to examine the genomic features of this specialized region, which
      resulted in the largest collection of contiguous genomic DNA sequences of a Y
      chromosome in flowering plants. Extreme gene paucity was observed in the papaya
      MSY with no functional gene identified in 715 kb MSY sequences. A high density of
      retroelements and local sequence duplications were detected in the MSY that is
      suppressed for recombination. Location of the papaya MSY near the centromere
      might have provided recombination suppression and fostered paucity of genes in
      the male specific region of the Y chromosome. Our findings provide critical
      information for deciphering the sex chromosomes in papaya and reference
      information for comparative studies of other sex chromosomes in animals and
      plants.

PMID- 17520293
TI  - Fluorescent in situ RT-PCR to visualise the expression of a phosphate transporter
      gene from an ectomycorrhizal fungus.
AB  - Expression of a mycorrhizal fungal-specific phosphate (P) transporter gene
      (HcPT1) was studied in mycelium of the ectomycorrhizal fungus Hebeloma
      cylindrosporum, by in situ reverse transcriptase polymerase chain reaction using
      amplification of complementary DNA sequences. The expression of HcPT1 was
      visualised under two different P treatments. Mycelium was transferred to liquid
      medium with or without P and incubated for 5 days. Under P starvation, mycelium
      growth and vitality was reduced and the expression of HcPT1 up regulated. Enzyme
      labelled fluorescent substrate was used to detect gene expression in situ with
      epi-fluorescence microscopy and to visualise it at the level of the individual
      hyphae both in starved and non-starved hyphae. Up-regulation of HcPT1 was
      observed as a more intense fluorescent signal and from the larger proportion of
      hyphae that showed expression.

PMID- 17520294
TI  - Fixed lumbar apical vertebral rotation predicts spinal decompensation in Lenke
      type 3C adolescent idiopathic scoliosis after selective posterior thoracic
      correction and fusion.
AB  - Retrospective radiographic review of surgically treated double major curves
      (Lenke type 3C) in adolescent idiopathic scoliosis. To evaluate the role of
      selective posterior thoracic correction and fusion in double major curves with
      third generation instrumentation and to identify preoperative radiographic
      parameters that predict postoperative coronal spinal decompensation.
      Traditionally the surgical treatment of double major curves consists of fusion of
      both the thoracic and the lumbar curve. Few attempt to perform selective thoracic
      fusion in this curve pattern because of the potential to create spinal imbalance.
      Thirty-six patients with Lenke type 3C curves underwent a selective posterior
      thoracic correction and fusion with either Cotrel-Dubousset instrumentation or
      the Universal Spine System. Radiographs were evaluated to assess coronal and
      sagittal balance, curve flexibility, and curve correction at a minimum follow up
      of 2 years. Postoperative coronal spinal decompensation was investigated with
      respect to preoperative radiographic parameters on standing anteroposterior (AP),
      standing lateral radiographs, thoracic and lumbar supine side-bending
      radiographs. Coronal spinal decompensation was defined as plumbline deviation of
      C7 of more than 2 cm with respect to the centre sacral vertical line (CSVL)
      within 2 years of surgery. Twenty-six patients (72%) showed satisfactory frontal
      plane alignment patients (28%) showed coronal spinal decompensation. Significant
      group differences, however, were identified for lumbar apical vertebral rotation,
      measured according to Perdriolle (La scoliose. Son etude tridimensionnelle.
      Maloine, Paris, pp 179, 1979) (A 16 degrees , B 22 degrees , P = 0.02),
      percentage correction (derotation) of lumbar apical vertebrae in lumbar supine
      side-bending films in comparison to standing AP radiographs (A 49%, B 27%, P =
      0.002) and thoracic curve flexibility (A 43%, B 25%, P = 0.03). High correlation
      was noted between postoperative decompensation and derotation of lumbar apical
      vertebrae in pre-operative lumbar supine side-bending films with a critical value
      of 40% (Pearson correlation coefficient; P = 0.62, P < 0.001). Ten of 36 patients
      (28%) with Lenke type 3C adolescent idiopathic scoliosis showed coronal spinal
      decompensation of more than 2 cm after selective posterior thoracic correction
      and fusion. Lumbar apical vertebral derotation of less than 40% provided the
      radiographic prediction of postoperative coronal spinal imbalance. We advise
      close scrutiny of the transverse plane in the lumbar supine bending film when
      planning surgical strategy.

PMID- 17520295
TI  - Acute L5 pedicle fracture and contralateral spondylolysis in a 12-year-old boy: a
      case report.
AB  - Acute unilateral L5 pedicle fracture associated with a pre-existing contralateral
      spondylolysis is a rare lesion. We report a case in a non-competitive 12-year-old
      boy. We present the clinical, radiological and specific management of this rare
      condition. The clinical and radiological draft of this patient was reviewed. The
      follow-up was 30 months after fracture healing. Some cases reported in the
      literature were analyzed and our clinical findings and therapeutic strategy was
      compared and discussed. Non-operative treatment was done including full-time
      bracing in a modified Boston brace incorporating one thigh for 3 months. Plain
      radiographs and computed tomographic (CT)-scan performed at 3 and 6 months showed
      progressive healing of the pedicle fracture and no modification of the
      contralateral isthmic spondylolytic lesion. At final follow-up, the patient was
      asymptomatic and resumed all his activities. In skeletally immature patients, we
      think that conservative treatment should be considered as a treatment option for
      this unusual injury.

PMID- 17520296
TI  - Pain regulation and health-related quality of life after thoracolumbar fractures
      of the spine.
AB  - Fractures of the thoracolumbar spine rank among the severest injuries of the
      human skeleton. Especially in younger patients they often result from high-energy
      accidents. Recently, a shift in paradigm towards more aggressive treatment
      strategies including anterior procedures could be observed. However, so far only
      few data exist reflecting the quality of life (QoL) after such injuries. The aim
      of this study was to evaluate medium-term QoL and further to identify factors
      that influence the clinical outcome in patients with fractures of the
      thoracolumbar spine. Data of 906 patients who were treated during a 10-year
      period in our institution were evaluated retrospectively. Only patients with
      single-level traumatic injuries aged between 18 and 65 years without neurological
      deficits, concomitant injuries of other locations and internal comorbidities were
      included into the investigation (n = 204). Three different treatment groups (i.e.
      non-operative, dorsal and dorsoventral stabilisation) were compared to healthy
      controls as well as different pain populations. The QoL was assessed using
      established questionnaires (SF-36, HFAQ, VAS-Spinescore, PRQ, and PTSD). Sixty
      five percent of the included patients (n = 133) were studied at an average follow
      up of 5.3 +/- 1.7 years after injury. All treatment groups revealed an identical
      gender and age distribution. More severe and unstable injuries were found in the
      surgical groups associated with higher treatment costs and a longer inability to
      work. Compared to healthy controls, QoL was compromised to the same extent in all
      groups. Furthermore, all patients treated in this study did significantly better
      than low back pain individuals with regard to QoL and pain regulation parameters.
      In our study, patients with thoracolumbar spine fractures showed a reduced QoL
      compared to healthy controls. Thus, patients do not seem to regain their former
      QoL. However, the level of discomfort was comparably low in all groups, even in
      patients with more severe injuries requiring extensive surgery. Overall, outcome
      and QoL after traumatic fractures of the thoracolumbar spine rather seem to be
      determined by the severity of injury than by pain regulation or other
      psychosocial factors which is likely the case in low back pain disorders.

PMID- 17520297
TI  - The outcome of spinal decompression surgery 5 years on.
AB  - Decompression surgery is an increasingly common operation for the treatment of
      lumbar spinal stenosis. Although good relief from leg pain is expected after
      surgery, long term results of pain relief and function are more uncertain. This
      study prospectively followed a cohort of patients presenting with the signs and
      symptoms of spinal stenosis, who underwent decompression surgery to ascertain the
      long term outcome with respect to pain and function using visual analogue pain
      scores, the Oswestry Disability Index, and the Short Form 36, a general health
      questionnaire. From an initial pool of 84 recruited patients, 7 withdrew from
      surgical intervention; of the remaining 77, 51 (66%) returned for follow up
      assessments at 5 years. In these responders, a significant improvement was
      observed in back and leg pain, which was sustained for at least 1 year (P <
      0.01). A significant improvement was also seen in physical function (P < 0.05) as
      assessed by Oswestry and SF-36. Although an initial improvement was noted in
      social function, this was not observed at 5 years. This study has demonstrated
      that decompression surgery is successful in relieving symptoms of lumbar spinal
      stenosis. Physical function, back and leg pain are significantly improved after 5
      years but initial significant improvements in social function diminish over time.

PMID- 17520298
TI  - Direct repair of defects in lumbar spondylolysis with a new pedicle screw hook
      fixation: clinical, functional and Ct-assessed study.
AB  - Spondylolysis is a common entity, a minority of people affected by this disease
      need medical care, and only a few require surgery. Reconstruction of the pars
      interarticularis is an interesting alternative to segmental fusion; this
      technique has the advantage of preserving segmental motion. Most authors report
      good results for young patients without intervertebral disk or facet degenerative
      changes. Moreover Louis also showed good to excellent results with his technique
      carried out among people who presented a satisfactory disk height (equal to two
      thirds of normal height). This could extend the number of patients for whom pars
      interarticularis repair could be proposed. In this study, the limit of
      reconstruction was set at grade 3 of the Pfirrmann's classification. The fixation
      of the isthmus was done with a new kind of pedicle screw hook system. This stable
      and strong device is easy to use, allows an anatomic pars interarticularis
      reconstruction of spondylolysis and avoids a postoperative bracing. Twenty-three
      patients were assessed in this study, the mean age at operation was 34 (range 16
      52 years) and the average follow-up was for 59 months (range 6-113 months). Eight
      patients showed moderate degenerative disk disease before the surgery and 12
      patients had a grade 1 spondylolisthesis. The visual analogical scale, the
      Oswestry disability index (ODI) and the modified Prolo score were used for
      assessment of pain and clinical outcome before and after surgery. The results
      were from "excellent" to "good" for twenty patients (87%) and "fair" for three of
      them (13%). The consolidation of the isthmus was assessed at the end of the study
      (CT-scan); the fusion rate was observed in 91%. Among patients aged less than 30
      years results are from "good", to "excellent" in all cases and consolidation was
      always observed. All of them showed normal disc signal before the surgery. In the
      group aged more than 30 years, the results varied from "good" to "excellent' in
      73% and fusion of the defect was discovered in 82% of cases. Eight of them (73%)
      had moderate disk signal modification before the surgery. All people with fair
      results displayed moderate disk degeneration signs at MRI before surgery; but two
      of those three patients had a failure of defect consolidation too and it is also
      associated with poor results by several authors. No complication was found in
      this series. According to the good results reported by Louis and upto the current
      finding, the authors believe that pars interarticularis repair can be carried out
      on patients with moderate degenerative disk disease; the stage 3 of Pfirrmann's
      classification seems a good limit. The Bone and joint research (B.J.R. system) is
      readily usable by any surgeon using pedicle screw systems and having a short
      learning curve. No device failure has been observed in this series.

PMID- 17520299
TI  - Elevated soluble receptor activator of nuclear factor-kappaB ligand and reduced
      bone mineral density in patients with adolescent idiopathic scoliosis.
AB  - Generalized low bone mass and osteopenia in both axial and peripheral skeleton in
      adolescent idiopathic scoliosis (AIS) have been reported in literature. However,
      the exact mechanisms and causes of the bone loss in AIS are not identified yet.
      Therefore, this study examined the relationship between serum concentration of
      soluble receptor activator of nuclear factor-kappaB ligand (RANKL), serum level
      of osteoprotegerin (OPG) and bone mass in 72 patients with AIS and compared to
      those of 64 age- and gender-matched healthy controls. The mean lumbar spinal bone
      mineral density (LSBMD) and femoral neck BMD (FNBMD) in patients with AIS were
      decreased compared with that in control individuals, respectively (P = 0.0029 and
      P = 0.0192, respectively). The mean RANKL and RANKL to OPG ratio in patients with
      AIS were increased compared with that in control subjects, respectively (P =
      0.0004 and P = 0.0032, respectively). The RANKL and RANKL to OPG ratios were
      negatively correlated to the LSBMD and serum OPG levels in both groups. Serum OPG
      levels were positively correlated to the LSBMD and FNBMD in both groups. These
      findings mean that the imbalance and the disturbed interaction of RANKL and OPG
      may be an important cause and pathogenesis in reduced BMD in AIS.

PMID- 17520300
TI  - Comment on the paper "Contralateral radiculopathy after transforaminal lumbar
      interbody fusion" (Travis Hunt et al.).

PMID- 17520301
TI  - Comment to the author's reply of J.-M. Mac-Thiong et al. regarding "A proposal
      for a surgical classification of pediatric lumbosacral spondylolisthesis based on
      current literature" [J.-M. Mac-Thiong, H. Labelle (2006) Eur Spine J 15:1425
      1435].

PMID- 17520302
TI  - Answer to the comment by Dietrich Schlenzka on ''A proposal for a surgical
      classification of pediatric lumbosacral spondylolisthesis based on current
      literature (J.-M. Mac-Thiong, H. Labelle)''.

PMID- 17520303
TI  - Determinants of cost-effectiveness in lumbar spinal fusion using the net benefit
      framework: a 2-year follow-up study among 695 patients.
AB  - Up to one third of patients undergoing lumbar spinal fusion show no improvement
      after the procedure and thus, despite evidence from RCTs, there might be a
      rationale for observational studies clarifying indications. Similarly, selection
      of the right patients for the right procedure could have significant impact on
      cost-effectiveness, which in some countries, in turn, affects whether procedures
      are to be available through the National Health Service. The aim of this study
      was to investigate determinants of cost-effectiveness in lumbar spinal fusion. An
      observational cohort study with 2-year follow-up was conducted: 695 patients who
      underwent lumbar spinal fusion from 1996 to 2002 were included and followed for 2
      years. Patients had a localized segmental pathology and were diagnosed with MRI
      verified isthmic spondylolisthesis (26%) or disc degeneration (74%). The surgical
      techniques were non-instrumented posterolateral fusion (14%), instrumented
      posterolateral fusion (54%), and circumferential fusion (32%). Societal costs and
      improvement in functional disability (Dallas Pain Questionnaire) were transformed
      into a net benefit measure. Classical linear regression of the net benefit was
      conducted using predictors of age, sex, diagnosis, duration of pain, smoking
      habits, occupational status, severity of disability, emotional distress, surgical
      technique, and number of levels fused. The main results were that two
      determinants were found to negatively influence net benefit: smoking and
      diagnosis, whereas two others were found to be positively associated with the net
      benefit: severe disability and emotional distress. In conclusion, predicting net
      benefit reverses the picture usually seen in studies predicting clinical
      outcomes, because the response variable is based on improvement over time rather
      than end-point measures alone. Smoking habits, diagnosis, pre-operative
      disability, and pre-operative emotional distress were found to be significantly
      associated with the net benefit of spinal fusion.

PMID- 17520304
TI  - Comparative evaluation of automated reading versus visual interpretation with the
      BBL Crystal enteric/nonfermenter identification system in a clinical setting.

PMID- 17520305
TI  - Modeling the mechanical consequences of vibratory loading in the vertebral body:
      microscale effects.
AB  - Osteoporosis affects nearly 10 million individuals in the United States.
      Conventional treatments include anti-resorptive drug therapies, but recently, it
      has been demonstrated that delivering a low magnitude, dynamic stimulus via whole
      body vibration can have an osteogenic effect without the need for large magnitude
      strain stimulus. Vibration of the vertebral body induces a range of stimuli that
      may account for the anabolic response including low magnitude strains,
      interfacial shear stress due to marrow movement, and blood transport. In order to
      evaluate the relative importance of these stimuli, we integrated a
      microstructural model of vertebral cancellous bone with a mixture theory model of
      the vertebral body. The predicted shear stresses on the surfaces of the
      trabeculae during vibratory loading are in the range of values considered to be
      stimulatory and increase with increasing solid volume fraction. Peak volumetric
      blood flow rates also varied with strain amplitude and frequency, but exhibited
      little dependence on solid volume fraction. These results suggest that fluid
      shear stress governs the response of the vertebrae to whole body vibration and
      that the marrow viscosity is a critical parameter which modulates the shear
      stress.

PMID- 17520306
TI  - The reduction of artifacts due to metal hip implants in CT-attenuation corrected
      PET images from hybrid PET/CT scanners.
AB  - CT beam hardening artifacts near metal hip implants may erroneously enhance or
      diminish radiotracer uptake following CT attenuation correction (AC) of PET
      images. An artifact reduction algorithm (ARA) was developed to reduce metal
      artifacts in CT-based AC-PET. The algorithm employed a Bayes classifier to
      identify beam-hardening artifacts, followed by a partial correction of the
      attenuation map. ARA was implemented on phantom and patient 18F-FDG studies using
      a clinical PET/CT scanner. In phantom studies ARA successfully removed two
      artifacts of erroneously elevated uptake near a stainless steel hip prosthesis
      which were depicted in the standard CT-AC PET. ARA has also identified two
      targets absent on the scanner PET images. Target-to-background ratios were 1.5-3
      times higher for ARA-PET than scanner images. In a patient study, metal artifacts
      were of lower intensity in ARA-PET as compared to standard images. Potentially,
      ARA may improve detectability of small lesions located near metal hip implants.

PMID- 17520307
TI  - Cytochrome P450-dependent metabolism of vitamin E isoforms is a critical
      determinant of their tissue concentrations in rats.
AB  - The aim of this study was to clarify the contribution of cytochrome P450 (CYP)
      dependent metabolism of vitamin E isoforms to their tissue concentrations. We
      studied the effect of ketoconazole, a potent inhibitor of CYP-dependent vitamin E
      metabolism in cultured cells, on vitamin E concentration in rats. Vitamin E
      deficient rats fed a vitamin E-free diet for 4 weeks were administered by oral
      gavage a vitamin E-free emulsion, an emulsion containing alpha-tocopherol, gamma
      tocopherol or a tocotrienol mixture with or without ketoconazole. Alpha
      tocopherol was detected in the serum and various tissues of the vitamin E
      deficient rats, but gamma-tocopherol, alpha- and gamma-tocotrienol were not
      detected. Ketoconazole decreased urinary excretion of 2,5,7,8-tetramethyl-2(2'
      carboxyethyl)-6-hydroxychroman after alpha-tocopherol or a tocotrienol mixture
      administration, and that of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman
      (gamma-CEHC) after gamma-tocopherol or a tocotrienol mixture administration. The
      gamma-tocopherol, alpha- and gamma-tocotrienol concentrations in the serum and
      various tissues at 24 h after their administration were elevated by ketoconazole,
      while the alpha-tocopherol concentration was not affected. The gamma-tocopherol
      or gamma-tocotrienol concentration in the jejunum at 3 h after each
      administration was also elevated by ketoconazole. In addition, significant amount
      of gamma-CEHC was in the jejunum at 3 h after gamma-tocopherol or gamma
      tocotrienol administration, and ketoconazole inhibited gamma-tocopherol
      metabolism to gamma-CEHC in the jejunum. These results showed that CYP-dependent
      metabolism of gamma-tocopherol and tocotrienol is a critical determinant of their
      concentrations in the serum and tissues. The data also suggest that some amount
      of dietary vitamin E isoform is metabolized by a CYP-mediated pathway in the
      intestine during absorption.

PMID- 17520308
TI  - Novel cyclopropane fatty acids from the phospholipids of the Caribbean sponge
      Pseudospongosorites suberitoides.
AB  - The cyclopropane fatty acids 17-methyl-trans-4,5-methyleneoctadecanoic acid, 18
      methyl-trans-4,5-methylenenonadecanoic acid, and 17-methyl-trans-4,5
      methylenenonadecanoic acid were characterized for the first time in nature in the
      phospholipids (mainly PE, PG and PS) of the hermit-crab sponge
      Pseudospongosorites suberitoides. Pyrrolidine derivatization was the key in
      identifying the position of the cyclopropyl and methyl groups in the acyl chains
      and (1)H NMR was used to determine the trans stereochemistry of the cyclopropane
      ring. The phospholipids from the sponge also contained an interesting series of
      iso-anteiso Delta(5,9) fatty acids with chain-lengths between 17 and 21 carbons,
      with the fatty acids (5Z,9Z)-18-methyl-5,9-nonadecadienoic acid and the (5Z,9Z)
      17-methyl-5,9-nonadecadienoic acid being described for the first time in sponges.
      The anteiso alpha-methoxylated fatty acid 2-methoxy-12-methyltetradecanoic acid
      was also identified for the first time in nature in the phospholipids of this
      interesting marine sponge. The novel cyclopropyl fatty acids could have
      originated from the phospholipids of a cyanobacterium living in symbiosis with
      the sponge.

PMID- 17520309
TI  - Unique perspectives on the obesogenic environment.

PMID- 17520313
TI  - Independency of myocardial stunning of endothelial stunning?
AB  - BACKGROUND AND OBJECTIVE: Vascular endothelial cells play an important role in
      the control of vascular tone. The reasons for coronary endothelial dysfunction
      are complex and may involve ischemia/reperfusion injury. We investigated whether
      endothelial, smooth muscle, and myocardial dysfunction are independent phenomena.
      METHODS: Rabbit hearts were rapidly excised without intermittent ischemia,
      connected to a modified Langendorff apparatus, and perfused with a modified Krebs
      Henseleit solution containing bovine erythrocytes. Normoxic control hearts (n =
      16) were perfused for 125 min. Postischemic hearts (n = 15) were perfused for 45
      min, submitted to global ischemia (20 min) and reperfused (60 min). Both the
      normoxic and the postischemic hearts were divided into three groups that received
      either 0.9% NaCl (placebo), or 3-morpholinosydnonimine (SIN-1; 100 microM),or
      substance P (SP; 5 nM). RESULTS: After SIN-1, CBF in the normoxic hearts was
      increased by maximum 63% and after SP by 62%. 60 min after the onset of
      reperfusion, the postischemic hearts of both groups had recovered to 95%
      LVP(max). In the postischemic hearts, SIN-1 increased CBF still by 58%, while the
      endothelium-dependent vasomotion was impaired: SP improved CBF by only 9%.
      SUMMARY AND CONCLUSIONS: The particular protocol permitted differentiation
      between myocardial and vascular stunning. The results show that, while myocardial
      function has already recovered, endothelial cells are more severely impaired than
      smooth muscle cells, and that this injury persists beyond myocardial stunning.
      Thus, endothelial-dependent dysfunction can still impair vasodilatation while
      ventricular dysfunction has already resolved.

PMID- 17520315
TI  - Gastric carcinoma: applying the sentinel node paradigm to improve the
      understanding of metastatic patterns and the possible role of selective
      lymphadenectomy.

PMID- 17520314
TI  - Protective effect of enzymatic extracts from microalgae against DNA damage
      induced by H2O2.
AB  - The enzymatic extracts from seven species of microalgae (Pediastrum duplex,
      Dactylococcopsis fascicularis, Halochlorococcum porphyrae, Oltmannsiellopsis
      unicellularis, Achnanthes longipes, Navicula sp. and Amphora coffeaeformis)
      collected from three habitats (freshwater, tidal pool, and coastal benthic) at
      Jeju Island in Korea were investigated for their antioxidant activity. Of the
      extracts tested, the AMG 300 L (an exo 1, 4-alpha-D-glucosidase) extract of P.
      duplex, the Viscozyme extract of Navicula sp., and the Celluclast extract of A.
      longipes provided the most potential as antioxidants. Meanwhile, the Termamyl
      extract of P. duplex in an H(2)O(2) scavenging assay exhibited an approximate 60%
      scavenging effect. In this study, we report that the DNA damage inhibitory
      effects of P. duplex (Termamyl extract) and D. fascicularis (Kojizyme extract)
      were nearly 80% and 69% respectively at a concentration of 100 microg/ml. Thus,
      it is suggested that the microalgae tested in this study yield promising DNA
      damage inhibitory properties on mouse lymphoma L 5178 cells that are treated with
      H(2)O(2). Therefore, microalgae such as P. duplex may be an excellent source of
      naturally occurring antioxidant compounds with potent DNA damage inhibition
      potential.

PMID- 17520316
TI  - Location of rectal cancer within the circumference of the rectum does not
      influence lymph node status.
AB  - BACKGROUND: Patients with rectal cancer are treated in multimodal concepts on the
      basis of their tumor stage. In the context of local excision, it is of major
      importance to assess the risk of lymph node metastases in patients with T1 or T2
      tumors. To identify patients with an increased risk of lymph node metastases, the
      influence of the location of the tumor within the rectum (anterior, posterior,
      lateral) and of other variables on lymph node status was investigated. METHODS:
      All consecutive patients undergoing low anterior resection or abdominoperineal
      resection for primary rectal cancer between October 2001 and September 2003 were
      included. A multivariate analysis was performed focussing on tumor location and
      other variables as potential predictive factors for lymph node metastases.
      RESULTS: Of 148 included patients, 135 (91%) had an anterior and 13 (9%) an
      abdominoperineal resection. All patients routinely underwent total mesorectal
      excision. A statistically significant correlation with positive lymph node status
      was found for patients with lymphatic invasion (P < .0001), higher T stage (P <
      .0001), presence of distant metastases (M1) (P = .0003), and circular growth of
      the tumor (P = .003), but not for tumor location. Multivariate analysis confirmed
      that patients without lymphatic invasion (odds ratio, .1; 95% confidence
      interval, .02-.48; P = .006) and with a low T stage (odds ratio, .07; 95%
      confidence interval, .002-.9; P = .004) have a significantly lower risk for
      positive lymph nodes. CONCLUSIONS: Location of rectal cancer (anterior,
      posterior, lateral) is not a good predictor for lymph node metastases.

PMID- 17520317
TI  - Heme oxygenase-1 gene promoter polymorphism is associated with risk of gastric
      adenocarcinoma and lymphovascular tumor invasion.
AB  - PURPOSE: Heme oxygenase-1 (HO-1) gene, which encodes an oxidative response
      protein, plays a role in cytoprotection. A (GT)n dinucleotide repeat in HO-1
      promoter is polymorphic and modulates the transcriptional activity of the gene. A
      HO-1 gene promoter polymorphism was reported to be associated with the risks of
      lung adenocarcinoma and oral squamous cancer. In this study, the correlation
      between the HO-1 gene promoter polymorphism and the clinicopathological
      characteristics, along with the risk of gastric cancer, was analyzed.
      EXPERIMENTAL DESIGN: We examined the genotypic frequencies of (GT)n repeats in
      183 gastric cancer patients and 250 control subjects by PCR-based genotyping and
      DNA sequencing. The length polymorphisms of (GT)n repeats were classified into
      short (S) component (n <or= 25), medium (M) component (26 <or= n <or= 30) and
      long (L) component (n >or= 31). The distribution of S, M and L components in
      patient and control groups were evaluated to determine the correlation with
      susceptibility and clinicopathological characteristics of gastric adenocarcinoma.
      RESULTS: Higher frequencies of L-allele, L-allele carrier (S/L, M/L, L/L) and S/L
      genotype were found in gastric cancer patients. The frequencies of M-allele, M
      allele carrier (M/M, M/L, M/S) and M/M genotype were significantly lower in
      patients with gastric cancer than controls. Furthermore, the frequency of
      lymphovascular tumor invasion was significantly lower in M-allele carriers
      compared to non-M-allele carriers (S/S, S/L, L/L) (p = 0.009). CONCLUSIONS: These
      findings suggest that the long (GT)n repeat of HO-1 gene promoter was associated
      with a higher frequency of gastric adenocarcinoma, and the medium (GT)n repeat
      might possess protective effect against gastric adenocarcinoma with a lower
      frequency of lymphovascular invasion in tumors.

PMID- 17520318
TI  - Cognitive estimation in mild Alzheimer's disease.
AB  - In everyday life, we often estimate rather than know. We investigated in an
      experimental approach modality-specific cognitive estimation in patients with
      mild Alzheimer's disease (AD). Estimation of weight, size, number, and time prior
      and subsequent to observation of a moving object was assessed in healthy controls
      (HC; n = 49; 62.5 +/- 7.8 years (mean +/- standard deviation); MMSE 29.2 +/- 1.1)
      and patients with AD (NINCDS-ADRDA, DSM IV; n = 42; 75.0 +/- 9.5 years; p < 0.001
      to HC; MMSE 22.8 +/- 2.9; p < 0.001 to HC). In HC none of the estimation tasks
      correlated with age or general intellectual ability. AD patients were impaired
      for estimation of time and weight while estimation of number, size, and distance
      was not impaired. Estimation of time that a marble will need to roll down a
      marble track was associated with lower scores for verbal fluency and higher
      scores for clock drawing in the AD group and estimation of time subsequent to
      observation was associated with higher scores in clock drawing. Time estimation
      for moving objects as well as the ability to correct oneself on observation is
      impaired in patients with very mild AD. This argues for caution in tasks such as
      car driving already in this stage. Errors in estimation of time observed indicate
      temporo-parietal impairment while errors on estimation prior to observation of
      the moving object indicate additional frontal lobe impairment.

PMID- 17520320
TI  - Proceedings of the 12th Amine Oxidase and Trace Amines Workshop, Rotterdam, The
      Netherlands, 2006.

PMID- 17520319
TI  - Cannabis and Ecstasy/MDMA (3,4-methylenedioxymethamphetamine): an analysis of
      their neuropsychobiological interactions in recreational users.
AB  - The majority of recreational Ecstasy/MDMA users (90-98%) also take cannabis. This
      co-drug usage is often viewed as a methodological confound, which needs to be
      removed statistically. Here we take a rather different approach, and debate the
      potential complexities of their psychobiological interactions. The ring
      substituted amphetamine derivate MDMA (3,4-methylendioxymethamphetmaine, or
      'Ecstasy') is a powerful CNS stimulant, whereas cannabis is a relaxant. Their co
      usage may reflect opposing effects in three psychobiological areas: arousal, body
      temperature, and oxidative stress. Firstly MDMA is alerting whereas cannabis is
      sedating. Secondly MDMA is hyperthermic whereas cannabis is hypothermic. Thirdly
      MDMA increases oxidative stress whereas cannabinoids are antioxidant. Hence
      cannabis may modulate the acute and sub-acute reactions to MDMA, reduce the acute
      hyperthermia induced by MDMA, and ameliorate the oxidative stress caused by MDMA.
      The limited empirical evidence on each topic will be critically examined. In
      terms of chronic effects each drug is functionally damaging, so that polydrug
      users generally display cumulative neurobiological impairments. However in
      certain aspects their neuropsychobiological effects may interactive rather than
      additive. In particular, the combined use of cannabis and MDMA may have rather
      different neuropsychobiological implications, than their separate usage. In order
      to investigate these potential complexities, future research will need better
      empirical data on the exact patterns of co-drug usage.

PMID- 17520321
TI  - Redirecting retroviral tropism by insertion of hepatitis B virus PreS1 core
      peptide into the envelope.
AB  - A potentially powerful approach for in vivo gene delivery is to target retroviral
      vectors to specific cells through interactions between cell surface receptors and
      appropriately engineered viral envelope proteins, but this has so far met with
      little success. We report here an attempt to target ecotropic MLV retroviral
      vectors to human cells infected by hepatitis B virus (HBV) through the
      interaction between the HBV PreS1 domain and the receptors on the cell surface.
      We examined 7 MLV chimeric envelope derivatives that contained either the HBV
      PreS1 peptide or PreS1 aa 21-47 segment (partial PreS1, pPreS1), which was
      inserted at various locations within the SU of the MoMLV Env. In addition to
      infecting host NIH 3T3 cells, some of pseudotyped viruses could transduce human
      cells. Our results demonstrate that short peptide ligands inserted at appropriate
      locations in the MLV envelope can selectively target retroviruses to human cells.

PMID- 17520322
TI  - High genetic identity between RNA 3 segments of an Old World isolate and a New
      World isolate of Maize stripe virus.

PMID- 17520324
TI  - Serum amino acid profile in patients with acute pancreatitis.
AB  - Patients in the early phase of acute pancreatitis (AP) have reduced serum levels
      of arginine and citrulline. This may be of patho-biological importance, since
      arginine is the substrate for nitric oxide, which in turn is involved in normal
      pancreatic physiology and in the inflammatory process. Serum amino acid spectrum
      was measured daily for five days and after recovery six weeks later in 19
      patients admitted to the hospital for acute pancreatitis. These patients had
      abnormal levels of most amino acids including arginine, citrulline, glutamine and
      glutamate. Phenylalanine and glutamate were increased, while arginine,
      citrulline, ornithine and glutamine were decreased compared to levels after
      recovery. NO(2)/NO(3) concentration in the urine, but not serum arginase
      activity, was significantly increased day 1 compared to day 5 after admission.
      Acute pancreatitis causes a disturbance of the serum amino acid spectrum, with
      possible implications for the inflammatory process and organ function both in the
      pancreas and the gut. Supplementation of selected amino acids could possibly be
      of value in this severe condition.

PMID- 17520325
TI  - Using pseudo amino acid composition to predict transmembrane regions in protein:
      cellular automata and Lempel-Ziv complexity.
AB  - Transmembrane (TM) proteins represent about 20-30% of the protein sequences in
      higher eukaryotes, playing important roles across a range of cellular functions.
      Moreover, knowledge about topology of these proteins often provides crucial hints
      toward their function. Due to the difficulties in experimental structure
      determinations of TM protein, theoretical prediction methods are highly preferred
      in identifying the topology of newly found ones according to their primary
      sequences, useful in both basic research and drug discovery. In this paper, based
      on the concept of pseudo amino acid composition (PseAA) that can incorporate
      sequence-order information of a protein sequence so as to remarkably enhance the
      power of discrete models (Chou, K. C., Proteins: Structure, Function, and
      Genetics, 2001, 43: 246-255), cellular automata and Lempel-Ziv complexity are
      introduced to predict the TM regions of integral membrane proteins including both
      alpha-helical and beta-barrel membrane proteins, validated by jackknife test. The
      result thus obtained is quite promising, which indicates that the current
      approach might be a quite potential high throughput tool in the post-genomic era.
      The source code and dataset are available for academic users at liml@scu.edu.cn.

PMID- 17520326
TI  - Oxygen dependence of tyrosine hydroxylase.
AB  - The effects of dioxygen on tyrosine hydroxylase (TH) activity was studied,
      measuring the formation of DOPA from tyrosine, (3)H(2)O from 3,5-(3)H-tyrosine,
      or by direct oxygraphic determination of oxygen consumption. A high enzyme
      activity was observed during the initial 1-2 min of the reactions, followed by a
      decline in activity, possibly related to a turnover dependent substoichiometrical
      oxidation of enzyme bound Fe(II) to the inactive Fe(III) state. During the
      initial reaction phase, apparent K (m)-values of 29-45 microM for dioxygen were
      determined for all human TH isoforms, i.e. 2-40 times higher than previously
      reported for TH isolated from animal tissues. After 8 min incubation, the K (m)
      (O(2))-values had declined to an average of 20 +/- 4 microM. Thus, TH activity
      may be severely limited by oxygen availability even at moderate hypoxic
      conditions, and the enzyme is rapidly and turnover dependent inactivated at the
      experimental conditions commonly employed to measure in vitro activities.

PMID- 17520327
TI  - Solid-phase peptide synthesis and circular dichroism study of chiral beta-peptoid
      homooligomers.
AB  - N-alkyl-beta-alanine oligomers (beta-peptoids) with alpha-chiral side chains [(R)
      or (S)-1-(phenylethyl)amino groups] were synthesized and analyzed by CD
      spectroscopy. These chiral beta-peptoid homomers exhibited chain-length-dependent
      and solvent-dependent ellipticity, strongly indicating the presence of a
      secondary structure in solution. The CD behaviour was only slightly temperature
      dependent upon heating, as also previously observed for stable alpha-peptoid
      helices containing the same type of side chains. Thus, the data presented here
      comprise the first evidence for a chain length-dependent secondary folding of
      compounds with this novel peptidomimetic backbone design. In addition,
      applicability of a novel hyphenated technique, HPLC-SPE-NMR/MS, for analysis of
      crude SPPS reaction products was demonstrated.

PMID- 17520328
TI  - The effect of taurine on polymorphonuclear leukocyte functions in endotoxemia.
AB  - The aim of the present study was to measure MPO activity in PMN leukocytes after
      endotoxin administration, and to compare the levels of NO2- competing with
      taurine for reaction with HOCl. Furthermore we aimed to determine TauCl levels, a
      product of MPO-H2O2-Halide system, and to evaluate anti-inflammatory properties
      of PMN in endotoxemia. In addition, our second objective was to investigate the
      effect of taurine, an antioxidant amino acid, on anti-bactericidal and anti
      inflammatory functions of PMN after administration of endotoxin together with
      taurine. All experiments were performed with four groups (control, taurine,
      endotoxemia, and taurine plus endotoxin) of ten guinea pigs. After endotoxin
      administration (4 mg/kg), MPO activities increased and taurine levels decreased.
      Therefore levels of TauCl, NO2*- increased. We observed the effects of taurine as
      conflicting. When taurine was administrated alone (300 mg/kg), all of these
      parameters decreased.Consequently, we suggested that taurine is influential in
      infected subjects but not on healthy ones as an antioxidative amino acid. In
      addition, we believe that in vivo effects of taurine may differ from those in
      vitro depending on its dosage.

PMID- 17520329
TI  - In silico analysis of arginine catabolism as a source of nitric oxide or
      polyamines in endothelial cells.
AB  - We use a modeling and simulation approach to carry out an in silico analysis of
      the metabolic pathways involving arginine as a precursor of nitric oxide or
      polyamines in aorta endothelial cells. Our model predicts conditions of
      physiological steady state, as well as the response of the system to changes in
      the control parameter, external arginine concentration. Metabolic flux control
      analysis allowed us to predict the values of flux control coefficients for all
      the transporters and enzymes included in the model. This analysis fulfills the
      flux control coefficient summation theorem and shows that both the low affinity
      transporter and arginase share the control of the fluxes through these metabolic
      pathways.

PMID- 17520330
TI  - Minilaparotomy cholecystectomy in children.
AB  - AIM: Scarcity of paediatric cholelithiasis limits the obtainable experience in
      paediatric laparoscopic cholecystectomy (LPC). We report minilaparotomy
      cholecystectomy (MLC) in children which may be a useful alternative to LPC
      avoiding the added cost of disposable laparoscopic equipment. METHODS: Nineteen
      cases underwent a retrograde MLC using a 2-4 cm transverse right upper quadrant
      incision. Various parameters were assessed. RESULTS: Mean age at presentation was
      10.87 years, mean length of the incision 2.8 cm, mean operative time 36.5 min,
      mean analgesic requirement 2 days, mean time to feed/ mobilize 1 day each, and
      mean duration of hospital stay was 2.7 days. All had satisfactory cosmetic result
      without postoperative complications. CONCLUSIONS: MLC in children involves a
      small incision, excellent cosmetic scar and rapid postoperative recovery at
      relatively low cost. It is a good alternative to LPC.

PMID- 17520331
TI  - Baseline correction of intraoperative electromyography using discrete wavelet
      transform.
AB  - OBJECTIVE: In intraoperative analysis of electromygraphic signals (EMG) for
      monitoring purposes, baseline artefacts frequently pose considerable problems.
      Since artefact sources in the operating room can only be reduced to a limited
      degree, signal-processing methods are needed to correct the registered data
      online without major changes to the relevant data itself. We describe a method
      for baseline correction based on "discrete wavelet transform" (DWT) and evaluate
      its performance compared to commonly used digital filters. METHODS: EMG data from
      10 patients who underwent removal of acoustic neuromas were processed.
      Effectiveness, preservation of relevant EMG patterns and processing speed of a
      DWT based correction method was assessed and compared to a range of commonly used
      Butterworth, Resistor-Capacitor and Gaussian filters. RESULTS: Butterworth and
      DWT filters showed better performance regarding artefact correction and pattern
      preservation compared to Resistor-Capacitor and Gaussian filters. Assuming equal
      weighting of both characteristics, DWT outperformed the other methods: While
      Butterworth, Resistor-Capacitor and Gaussian provided good pattern preservation,
      the effectiveness was low and vice versa, while DWT baseline correction at level
      6 performed well in both characteristics. CONCLUSIONS: The DWT method allows
      reliable and efficient intraoperative baseline correction in real-time. It is
      superior to commonly used methods and may be crucial for intraoperative analysis
      of EMG data, for example for intraoperative assessment of facial nerve function.

PMID- 17520332
TI  - Pretreatment with sarafotoxin 6c prior to coronary occlusion protects against
      infarction and arrhythmias via cardiomyocyte mitochondrial K(ATP) channel
      activation in the intact rabbit heart during ischemia/reperfusion.
AB  - BACKGROUND: Endothelial ET(B) receptor activation by exogenously administered
      sarafotoxin 6c(a snake venom peptide with a sequence homology to ET-1 prior to
      ischemia activates release of nitric oxide(NO) and previous studies have shown
      that NO facilitates mitochondrial K(ATP) activation in cardiac cells and
      cardioprotection. OBJECTIVES AND METHODS: The aim of this investigation was to
      test whether the administration of sarafotoxin 6c(a selective ET(B) receptor
      agonist) has cardioprotective and antiarrhythmic effects against ischemia and
      reperfusion injury in a well-standardized model of reperfusion arrhythmias in
      anesthetized adult male rabbits (n = 53) subjected to 30 min occlusion of the
      left coronary artery followed by 120 min of reperfusion. RESULTS: Pretreatment
      with sarafotoxin 6c (0.24 nmol/kg, i.v.) prior to the period of coronary
      occlusion offers significant infarct size reduction (19.1 +/- 2.0% versus 39.7 +/
      3.7% in the saline control group; P < 0.01) and antiarrhythmic effects.
      Sarafotoxin 6c treatment significantly attenuated the incidence of life
      threatening arrhythmias like sustained VT (13 versus 100% in the saline control
      group; P < 0.005) and other arrhythmias (25 versus 100% in the saline control
      group; P < 0.005), and increased the number of surviving animals without
      arrhythmias. Pretreatment with 5-HD but not HMR 1883 abolished the beneficial
      effects of sarafotoxin 6c on reperfusion induced arrhythmias and cardioprotection
      suggesting that benefits have been achieved via the selective activation of
      cardiomyocyte mitochondrial K(ATP) channels. Sarafotoxin 6c evoked NO release and
      selective activation of mitoK(ATP) channels in cardiomyocytes contributes to
      cardioprotection and antiarrhythmic activity during ischemia-reperfusion in the
      anesthetized rabbit. CONCLUSIONS: We conclude that the selective activation of
      ET(B) receptors by sarafotoxin 6c prior to coronary occlusion contributes to
      cardioprotective and antiarrhythmic properties.

PMID- 17520334
TI  - Associations of leisure-time physical activity with quality of life in a large,
      population-based sample of colorectal cancer survivors.
AB  - OBJECTIVE: To examine the associations between physical activity and quality of
      life for colorectal cancer survivors; and to describe the associations of medical
      and sociodemographic attributes with overall quality of life, and their
      moderating effects on the relationships between physical activity and quality of
      life. METHODS: Telephone interviews were conducted with 1,996 colorectal cancer
      survivors recruited through the Queensland Cancer Registry. Data were collected
      on current quality of life; leisure-time physical activity pre- and post
      diagnosis; cancer treatment and side-effects; and general sociodemographic
      attributes. Hierarchical generalized linear models identified variables
      significantly associated with quality of life. RESULTS: After controlling for
      sociodemographic variables, disease-specific variables, treatment side-effects,
      and pre-diagnosis leisure-time physical activity, there were significant
      differences in quality of life scores by post-diagnosis physical activity
      category. Compared to participants who were inactive after their diagnosis, those
      who were sufficiently active had a 17.0% higher total quality of life score.
      Physical activity also had a significant independent positive association with
      the physical well-being, functional well-being, and additional concerns subscales
      of the FACT-C. CONCLUSIONS: Our findings demonstrate that quite modest changes in
      leisure-time physical activity are associated with quality of life. Colorectal
      cancer survivors may benefit from a more active lifestyle.

PMID- 17520333
TI  - The protective effect of a purified extract of Withania somnifera against
      doxorubicin-induced cardiac toxicity in rats.
AB  - The therapeutic value of doxorubicin as an effective antineoplastic agent is
      limited by its cardiotoxic side-effects. The administration of doxorubicin (10
      mg/kg) to male Wistar rats induced necrosis and apoptosis in heart tissues. It
      also caused oxidative stress damage as evidenced by the elevation of
      malondialdehyde and protein carbonyl levels and catalase activity, accompanied by
      the concurrent depletion of total antioxidant capacity and of superoxide
      dismutase level in cardiac tissues. The doxorubicin-induced cardiotoxicity and
      oxidative stress damage were also accompanied by increases of myeloperoxidase
      activity, total calcium content, and the expression of Bcl-2 protein in heart
      tissues. Most of these doxorubicin-induced biochemical and histological
      alterations were effectively attenuated by prior administration of purified
      standardized extract (1.5% withanolides; manufactured by Idea Sphere Inc.,
      American Fork, UT, USA) of Withania somnifera (300 mg/kg). Thus, Withania may
      play a role in the protection against cardiotoxicity and thus might be a useful
      adjuvant therapy where doxorubicin is the cancer-treating drug.

PMID- 17520335
TI  - Occupation and risk of lung cancer in Central and Eastern Europe: the IARC multi
      center case-control study.
AB  - OBJECTIVE: We sought to evaluate the role of occupation and industry in lung
      carcinogenesis in six countries in Central and Eastern Europe. METHODS: This
      multi-center case-control study included 2,056 male and 576 female lung cancer
      incidence cases diagnosed from 1998 to 2001 and 2,144 male and 727 female
      controls frequency-matched for sex and age. Unconditional regression models were
      applied to calculate the odds ratios after controlling for potential confounders
      including age (5-year groups), study center (15 centers), and tobacco pack-years.
      RESULTS: Elevated odds ratios (ORs) were found for men employed as production
      workers (OR 1.45, 95% CI 1.22-1.72), bookkeepers and cashiers (1.81, 1.03-3.24),
      general farmers (1.67, 1.08-2.60), livestock workers (2.54, 1.09-5.88), miners
      (2.17, 1.47-3.23), toolmakers and metal patternmakers (2.56, 1.34-4.94), glass
      formers (2.55, 1.18-5.50), dockworkers, and freight handlers (1.49, 1.04-2.12).
      Industries with elevated risk among men included mining (1.75, 1.20-2.57),
      manufacture of cement, lime, or plaster (3.62, 1.11-12.00), casting of metals
      (2.00, 1.17-3.45), manufacture of electric motors (2.18, 1.24-3.86). For women,
      elevated ORs were found for medical, dental, veterinary doctors (2.54, 1.01
      6.31), librarians and curators (7.03, 1.80-27.80), sewers 3.63 (1.12-10.23).
      CONCLUSIONS: This study identifies new areas for further, explanatory analyses,
      especially in production work, and indicates new possible sources of exposure to
      cancer risk for women.

PMID- 17520336
TI  - Extraction of labile metals from solid media by dilute hydrochloric acid.
AB  - Extraction of labile metals from solid media is environmentally more meaningful
      than a total digestion. A variety of reagents have been introduced in the
      literature, but dilute HCl has received the greatest attention. We compare metal
      concentrations liberated by a dilute HCl leach with the sum of the 3-step
      optimized (standardized) BCR sequential extraction procedure. This is the first
      study to compare these procedures over a range of grain sizes. Road-deposited
      sediments from 10 sites in Honolulu were fractionated into six grain size
      classes. Aliquots of individual fractions were digested with dilute HCl, the 3
      step BCR procedure ('labile'), and a 4-acid (total) procedure. Results indicated
      that the weighted labile concentrations of Al, Cu, Fe, Mn, Ni, Pb and Zn were
      statistically greater than those from the dilute HCl leach. However, regression
      analysis indicated strong statistically significant relationships between the two
      partial extraction procedures for all metals. On a whole-sample basis, the
      toxicity classifications for anthropogenic-enhanced metals (Cu, Pb and Zn) were
      similar between extractions. Taken together, results suggest that the application
      of dilute HCl to solid media provides a rapid, cost-effective, and
      environmentally meaningful approach for contaminant monitoring.

PMID- 17520337
TI  - Forest cover change and fragmentation using Landsat data in Macka State Forest
      Enterprise in Turkey.
AB  - Monitoring forest cover change and understanding the dynamic of forest cover is
      increasingly important in sustainable development and management of forest
      ecosystems. This paper uses remote sensing (RS) techniques to monitor forest
      cover change in Macka State Forest Enterprise (MSFE) located in NE of Turkey
      through 1975 to 2000 and then analyses spatial and temporal changes in forest
      cover by Geographical Information Systems (GIS) and FRAGSTATStrade mark. Forest
      cover changes were detected from a time series of satellite images of Landsat MSS
      in 1975, Landsat TM in 1987, and Landsat ETM+ in 2000 using RS and GIS. The
      results showed that total forest area, productive forest area and degraded forest
      area increased while broadleaf forest area and non forest area decreased. Mixed
      forest and degraded forest increased during the first (1975-1987) period, but
      decreased during the second (1987-2000) period. During the whole study period,
      the annual forestation rate was 152 ha year(-1), equivalent to 0.27% year(-1)
      using the compound-interest-rate formula. The total number of patches increased
      from 36,204 to 48,092 (33%), and mean size of forest patch (MPS) decreased from
      2.8 ha to 2.1 ha during a 25 year period. Number of smaller patches (patches in 0
      100 ha size class) increased, indicating more fragmented landscape over time that
      might create a risk for the maintenance of biodiversity of the area. While total
      population increased from 1975 to 2000 (3.7%), rural population constantly
      decreased. The increase of forest areas may well be explained by the fact that
      demographic movement of rural areas concentrated into Macka City Center. These
      figures also indicated that decrease in the rural population might likely lead to
      the release of human pressure to forest areas, probably resulting in a positive
      development of forest areas.

PMID- 17520338
TI  - Current status and perspectives of accelerated carbonation processes on municipal
      waste combustion residues.
AB  - The increasing volumes of municipal solid waste produced worldwide are
      encouraging the development of processes to reduce the environmental impact of
      this waste stream. Combustion technology can facilitate volume reduction of up to
      90%, with the inorganic contaminants being captured in furnace bottom ash, and
      fly ash/APC residues. The disposal or reuse of these residues is however governed
      by the potential release of constituent contaminants into the environment.
      Accelerated carbonation has been shown to have a potential for improving the
      chemical stability and leaching behaviour of both bottom ash and fly ash/APC
      residues. However, the efficacy of carbonation depends on whether the method of
      gas application is direct or indirect. Also important are the mineralogy,
      chemistry and physical properties of the fresh ash, the carbonation reaction
      conditions such as temperature, contact time, CO(2) partial pressure and relative
      humidity. This paper reviews the main issues pertaining to the application of
      accelerated carbonation to municipal waste combustion residues to elucidate the
      potential benefits on the stabilization of such residues and for reducing CO(2)
      emissions. In particular, the modification of ash properties that occur upon
      carbonation and the CO(2) sequestration potential possible under different
      conditions are discussed. Although accelerated carbonation is a developing
      technology, it could be introduced in new incinerator facilities as a "finishing
      step" for both ash treatment and reduction of CO(2) emissions.

PMID- 17520339
TI  - Uric acid changes in urine and plasma: an effective tool in screening for purine
      inborn errors of metabolism and other pathological conditions.
AB  - Purine inborn errors of metabolism (IEM) are serious hereditary disorders, which
      should be suspected in any case of neonatal fitting, failure to thrive, recurrent
      infections, neurological deficit, renal disease, self-mutilation and other
      manifestations. Investigation usually starts with uric acid (UA) determination in
      urine and plasma. UA, the final product of purine metabolism in humans, may be
      altered not only in purine IEM, but also in other related pathologies and
      clinical conditions. However, data and information about abnormal UA levels are
      scattered in the literature, often being controversial and confusing. A
      comprehensive overview has been elaborated, according to abnormal UA levels in
      urine and plasma, which associates these alterations with purine IEM. Other
      possible diseases, clinical conditions, diet and drug intake, related to the
      metabolism of uric acid, are also presented. The article includes tables that
      classify the disorders according to different patterns of UA alterations, with
      pertinent enzymes, clinical symptoms, inheritance and comments. Additionally,
      summarized pathophysiological mechanisms of important disorders are described.
      The overview is intended to assist in the interpretation of the results of UA
      analyses. It demonstrates that variation of UA concentrations in urine and plasma
      may constitute an effective tool in screening for purine IEM and other related
      pathological conditions.

PMID- 17520340
TI  - Cytobrush-culture method to diagnose tinea capitis.
AB  - This is a comparative study to isolate the dermatophytes of tinea capitis using
      the cytobrush and comparing it versus the standard method. A prospective,
      observational, comparative trial of 178 probable cases of tinea capitis was
      conducted in two dermatological centers. Each patient underwent mycological tests
      that included direct exam with KOH and cultures with either of two methods:
      scraping the scalp to remove hair and cell debris, and the cytobrush. A total of
      135 clinically and mycologically proven cases of tinea capitis were included; 119
      were non-inflammatory and 16 inflammatory tinea. A total of 131 had a positive
      direct exam and subsequent primary isolation cultures were obtained in 135 cases.
      The main dermatophytes isolated were Microsporum canis (68%) and Trichophyton
      tonsurans (20%). A total of 115/135 (85.1%), were detected with the traditional
      method, with an average of 11.2 days until positive, while the number detected
      with the cytobrush was 132/135 (97.7%) with an average of 8.5 days until
      positive. The chi-square statistical method showed that the cytobrush culture was
      superior to the standard one with a chi-square of 5.078 (P = 0.025), with a
      statistically significant difference versus the standard method.

PMID- 17520341
TI  - Pigmentation in Black-boned sheep (Ovis aries): association with polymorphism of
      the Tyrosinase gene.
AB  - Measurements were made in Black-boned (n = 40) and normal (n = 23) sheep (Ovis
      aries) from a flock in Nanping County of Yunnan Province, China, as well as a
      group (n = 21) of Romney Marsh sheep (O. aries) with the view to explaining the
      basis of the dark pigmentation occurring in the Black-boned animals. Plasma
      colour was significantly darker (P < 0.01) in Black-boned sheep than in their
      normal flock mates, which in turn had significantly darker plasma (P < 0.01) than
      the Romney Marsh sheep. Similar significant (P < 0.01) differences were measured
      for plasma tyrosinase activity and both groups of sheep from Nanping County had
      similar plasma concentrations of glutathione which were significantly smaller (P
      < 0.01) than for the Romney Marsh sheep.A partial fragment of 750 bp of exon 1 of
      the gene encoding tyrosinase was constructed and found to contain two silent
      mutation sites (G192C and C462T) but there was no effect on amino acid sequences
      of tyrosinase. Using restriction fragment length polymorphism analyses two
      allelic variants of site G192C were identified giving rise to the genotypes GG,
      GC and CC; the frequencies of allele G being 0.914, 0.824 and 0.286 in the Black
      boned sheep, their flock mates and the Romney Marsh sheep respectively. Plasma
      tyrosinase activity was similar for genotypes GG and GC and for both genotypes
      significantly higher (P < 0.05) than for genotype CC. The sheep from Nanping
      County displayed only the GG and GC genotypes and had predominantly black or
      black and white coat colour whereas the Romney Marsh sheep were of either
      genotype GC or CC and exhibited only white coat colouration. It is not appears
      that the dark pigmentation of the Black-boned sheep arises because of
      polymorphisms in the exon 1 of tyrosinase gene. However, this result could
      explain the differences between Black-boned and Romney Marsh sheep but not for
      differences between Black-boned and Nanping Normal sheep. Moreover, this result
      has provided evidence of genetic markers in the form of polymorphisms of the
      tyrosinase gene which may help to find the black traits causing mutations. There
      would be merit in further studies using histochemical and molecular techniques to
      elucidate the causes of the dark pigmentation in these Black-boned sheep.

PMID- 17520342
TI  - Molecular characterization and expression analysis of OsBISERK1, a gene encoding
      a leucine-rich repeat receptor-like kinase, during disease resistance responses
      in rice.
AB  - A rice gene, OsBISERK1, encoding a protein belonging to SOMATIC EMBRYOGENESIS
      RECEPTOR KINASE (SERK) type of leucine-rich repeat receptor-like kinases (LRR
      RLKs) was identified. The OsBISERK1 encodes a 624 aa protein with high level of
      identity to known plant SERKs. OsBISERK1 contains a hydrophobic signal peptide, a
      leucine zipper, and five leucine-rich repeat motifs in the extracellular domain;
      the cytoplasmic region carries a proline-rich region and a single transmembrane
      domain, as well as a conserved intracellular serine/threonine protein kinase
      domain. OsBISERK1 has a low level of basal expression in leaf tissue. However,
      expression of OsBISERK1 was induced by treatment with benzothiadiazole (BTH),
      which is capable of inducing disease resistance in rice, and also up-regulated
      after inoculation with Magnaporthe grisea in BTH-treated rice seedlings and
      during incompatible interaction between a blast-resistant rice genotype and M.
      grisea. The results suggest that OsBISERK1 may be involved in disease resistance
      responses in rice.

PMID- 17520343
TI  - Regulation of healthcare ethics committees in Europe.
AB  - In this article, the question is discussed if and how Healthcare Ethics
      Committees (HECs) should be regulated. The paper consists of two parts. First,
      authors from eight EC member countries describe the status quo in their
      respective countries, and give reasons as to the form of regulation they consider
      most adequate. In the second part, the country reports are analysed. It is
      suggested that regulation of HECs should be central and weak. Central regulation
      is argued to be apt to improve HECs' accountability, relevance and comparability.
      To facilitate biomedical citizenship and ethical reflection, regulation should at
      the same time be weak rather than strict. Independence of HECs to deliberate
      about ethical questions, and to give solicited and unsolicited advice, should be
      supported and only interfered with by way of exception. One exception is when
      circumstances become temporary adversarial to ethical deliberation in healthcare
      institutions. In view of European unification, steps should be taken to develop
      consistent policies for both Eastern and Western European countries.

PMID- 17520344
TI  - Information recovery in cancer families: value for risk estimations.
AB  - BACKGROUND: Drawing an informative pedigree is fundamental in genetic
      counselling. It is very common for some parts of pedigrees to remain ambiguous
      because of the proband's inability to recall the past history of her/his family.
      Current age, date of birth, date of death and age of diagnosis are the commonest
      missing information in pedigrees. METHODS: The Scottish Social Statistics
      website, National Statistics website and English language literature were used to
      model extrapolations. About 172 Grampian families and three high-risk Grampian
      families with complete information were chosen to evaluate the influence of
      extrapolations on models' performance. Differences between original data and
      extrapolated data were assessed by independent samples t-test. RESULTS: Changes
      made by extrapolations in age- and cancer-related information were not
      statistically significant (P > 0.05) in comparison with original data, except for
      average age of diagnosis of breast cancer (P = 0.03). The differences made by
      extrapolations in estimated probabilities generated by probability assessment
      models were small and ignorable except that for Tyrer-Cuzick model for Grampian
      family 3. CONCLUSION: Extrapolations based on National Health Statistics can
      scientifically cover missing information in a defined population with minimum
      effect on performance of probability assessment models.

PMID- 17520345
TI  - Prognostic value of BRCA1 mutations in familial breast cancer patients affected
      by a second primary cancer.
AB  - The aim of this prospective study is to assess the prognostic value of BRCA1
      mutations in familial breast cancer patients affected by a second primary cancer.
      The study group comprised 19 women having multiple primary breast cancers (breast
      breast, breast-other primary) who were either BRCA1 mutation carriers, or not.
      Appearance of a second primary cancer was recognised as the event and survival
      and second primary free cancer survival was calculated from the date of diagnosis
      to the secondary primary cancer. The results of this study show that the event
      free survival of women with familial breast cancer affected by a second primary
      cancer, who are BRCA1 mutation carriers is better, compared with women from the
      general population with breast cancer selected for second primary cancer sites
      and all second primary sites -- P = 0.009 and P = 0.0078 respectively. In
      contrast, the event free survival of women with breast cancer affected by a
      second primary cancer, without a breast cancer family history, who are not BRCA1
      mutation carriers is the same, as for women from the general population with
      breast cancer selected for second primary cancer sites and all second primary
      sites -- P = 0.6417 and P = 0.4859 respectively. The median time from diagnosis
      of the first to second primary cancer in the mutation carrying, and non-carrying,
      groups was 8,7 and 1,9 years respectively. In the study group, the highest event
      free survival rates had been observed among those carrying the said mutations --
      66.7% at 5 years, and 33.3% at 10 years -- in contrast with those not carrying
      the mutations, with rates of 30.8% and 15.4% respectively.

PMID- 17520347
TI  - Open letter.

PMID- 17520348
TI  - Patient perspectives on the Poole PCT cancer genetics service.
AB  - Focussing on the primary care aspects of the Kenilworth model, the Poole Primary
      Care Trust (PCT) cancer genetics service has aimed to develop a high quality
      primary care-led service for the assessment and counselling of people concerned
      about their genetic risk of cancer. The service has been available through
      General Practitioner (GP) surgeries within the PCT since early 2006, and is
      delivered by Community Cancer Nurses as part of their role to provide proactive
      care and support to cancer patients, their families and the local population.
      Acting as a point of reference for cancer genetics at each practice, the nurses
      have supplied basic education to both health professionals and lay staff about
      the aims of the service and the genetic risk of cancer. Feedback from service
      users is one of the key elements of the Poole evaluation. This article is based
      on the views of some of the first patients referred. The patients consulted one
      of the cancer nurses between June and December 2006, and were interviewed by a
      researcher about their experience. The interviews focussed on the psychosocial
      aspects of the patients' experiences, which are less accessible through
      quantitative methods. The patients were encouraged to talk specifically and
      generally about their experiences, and described some of the feelings and
      emotions from the time of their referral onwards.

PMID- 17520349
TI  - Providing a community-based cancer risk assessment service for a socially and
      ethnically diverse population.
AB  - BACKGROUND: Patients from ethnic minorities are under-represented in referrals to
      cancer genetics services. In a regional genetics centre that serves two London
      boroughs, the existing service attracts 3% of its referrals from Black and
      Minority Ethnic (BME) and other ethnic groups, despite the fact that these groups
      make up 34% of the population. OBJECTIVES: To improve access to familial cancer
      risk assessment in a socially and ethnically diverse population. SETTING: The
      London boroughs of Lambeth and Southwark. DESIGN: Community-based, nurse-led
      clinics were established for people who were concerned about their familial
      cancer risk. Patients were asked to triage themselves by answering three
      questions. Self-referral was encouraged. MAIN OUTCOME MEASURES: Data were
      gathered on ethnicity of clients, cancer risk, source of referral and patient and
      health professional satisfaction with the service. RESULTS: Of the 415 people who
      have accessed the service, 46% were from not White British groups and 67%
      referred themselves to the service, demonstrating the success of this model in
      reaching 'hard to reach' groups. Thirty-seven percent of patients were assessed
      as being at population risk and 63% were assessed as being at moderate risk or
      higher, showing that the clinics were meeting an unmet need in the community.

PMID- 17520350
TI  - Cancer genetics in rural primary care: a pilot nurse-led service using a new
      mobile IT system.
AB  - Somerset has a relatively high incidence of cancer. The county is very rural with
      pockets of deprivation and sizeable areas of poor access to services. The Cancer
      Plan advocates early identification of cancer and identified the genetic
      revolution as having the potential to predict risk, and detect and diagnose
      cancer early. This innovative Public Health led pilot takes specialist cancer
      genetics services into primary care. It explores a new service model that is
      patient focused, provides services close to home and reduces hospital visits and
      pressure on genetics departments. People who believe they are at increased risk
      of developing cancer, due to family history, are assessed by nurse specialists at
      their local surgery and triaged into population, medium and high risk groups.
      Patient pathways have been streamlined for breast, ovarian and colorectal
      cancers, which are known to have a genetic link and there may be advantage in
      increased surveillance and/or genetic testing. People are given the opportunity
      to understand their personal level of risk and make choices about lifestyles and
      interventions. To support the delivery of cancer genetics services in primary
      care a bespoke software package has been developed building on a commercial
      programme already established in many genetics departments. Electronic
      transmission of pedigrees from primary to tertiary care assists the lean pathways
      and the incorporation of a new risk calculator based on NICE guidelines for
      familial breast cancer is being assessed.

PMID- 17520351
TI  - Improving access to cancer genetics services in primary care: socio-economic data
      from North Kirklees.
AB  - A primary care cancer genetics project, funded by Macmillan Cancer Support and
      the Department of Health, has been running in North Kirklees since 2004. North
      Kirklees has a high ethnic minority population (mainly South Asian) and 50% of
      its wards lie in the most deprived quintiles in England. Previous audits in the
      department of genetics have shown lower than expected referral rates for patients
      from lower socio-economic classes and no referrals from ethnic minority patients.
      The aims of the project included improving access to cancer genetics services for
      disadvantaged patients from lower socio-economic groups and the ethnic minority
      population. A practice nurse and a General Practitioner with a Special Interest
      in genetics, both with appropriate language skills, and a 0.5 FTE genetic
      counsellor have set up local clinics in several primary care sites in North
      Kirklees where they provide full genetic counselling services in the community.
      Demographic details, ethnic origin and education information are collected from
      each patient seen. Comparing information prior to and during the project
      demonstrates an increase in numbers of referrals for patients from lower socio
      economic classes, those with educational achievements at GCSE level or below, and
      those from South Asian backgrounds. Local clinics and increasing awareness of
      cancer genetics services for professionals and the public can improve access to
      such services.

PMID- 17520352
TI  - National evaluation of NHS genetics service investments: emerging issues from the
      cancer genetics pilots.
AB  - In seeking to fulfil the ambition of the 2003 genetics white paper, Our
      Inheritance, Our Future, to 'mainstream' genetic knowledge and practices, the
      Department of Health provided start-up funding for pilot services in various
      clinical areas. These included seven cancer genetics projects, co-funded with
      Macmillan Cancer Support. To help to understand the challenges encountered by
      such an attempt at reconfiguring the organization and delivery of services in
      this field, a programme-level evaluation of the genetics projects was
      commissioned to consider the organizational issues faced. Using a qualitative
      approach, this research has involved comparative case-study work in 11 of the
      pilot sites, including four of the seven cancer genetics pilots. In this paper,
      the researchers present early findings from their work, focusing in particular on
      the cancer genetics pilots. They consider some of the factors that have
      influenced how the pilots have sought to address pre-existing sector,
      organizational and professional boundaries to these new ways of working. The
      article examines the relationship between these factors and the extent to which
      pilots have succeeded in setting up boundary-spanning services, dealing with
      human-resource issues and creating sustainable, 'mainstreamed' provision which
      attracts ongoing funding in a volatile National Health Service commissioning
      environment where funding priorities do not always favour preventive, risk
      assessment services.

PMID- 17520353
TI  - Competences, education and support for new roles in cancer genetics services:
      outcomes from the cancer genetics pilot projects.
AB  - In 2004 the Department of Health in collaboration with Macmillan Cancer Support
      set up service development projects to pilot the integration of genetics in
      mainstream medicine in the area of cancer genetics.In developing these services,
      new roles and responsibilities were devised that required supporting programmes
      of education and training. The NHS National Genetics Education and Development
      Centre has worked with the projects to draw together their experience in these
      aspects. New roles include the Cancer Family Nurse Specialist, in which a nurse
      working in a cancer setting was trained to identify and manage genetic or family
      history concerns, and the Genetic Risk Assessment Practitioner--a small team of
      practitioners working within a secondary care setting to deliver a standardised
      risk assessment pathway. Existing roles were also adapted for a different
      setting, in particular the use of genetic counsellors working in a community
      ethnic minority setting. These practitioners undertook a range of clinical
      activities that can be mapped directly to the 'UK National Workforce Competences
      for Genetics in Clinical Practice for Non-genetics Healthcare Staff' framework
      developed by Skills for Health and the NHS National Genetics Education and
      Development Centre (2007; draft competence framework). The main differences
      between the various roles were in the ordering of genetic tests and the provision
      of advice on invasive preventive options such as mastectomy. Those involved in
      service development also needed to develop competences in project management,
      business skills, audit and evaluation, working with users, general management
      (personnel, multi-agency work and marketing), educational supervision, IT, public
      and professional outreach, and research. Important resources to support the
      development of new roles and competences included pathways and guidelines, a
      formal statement of competences, a recognised syllabus, appropriate and timely
      courses, the availability of a mentor, supervision and opportunities to discuss
      cases, a formal assessment of learning and continuing support from specialist
      genetics services. This represents a current resource gap that will be of concern
      to cancer networks and a challenge to providers of educational resources and
      regional genetics services.

PMID- 17520354
TI  - The role of patient users in cancer genetics services in primary care.
AB  - There is much research that suggests all aspects of health care in the National
      Health Service should have patient user experience and input. This is to make
      sure service provision meets the needs of the local population. The Oldham Cancer
      Genetics team felt this was very important when developing a new service.
      Involving "patient users" meant the service kept the "client" at the centre of
      the planning process. It ensured all locally produced leaflets, family history
      questionnaires and patient pathways were tailored to the needs of people in
      Oldham. The "patient users" were invaluable at awareness-raising sessions for
      both health professionals and Oldhamers as personal experience always offers
      maximum impact.

PMID- 17520355
TI  - Potent inhibition of HIV-1 replication by backbone cyclic peptides bearing the
      Rev arginine rich motif.
AB  - Due to its essential role in the virus life cycle, the viral regulatory protein
      Rev constitutes an attractive target for the development of new antiviral
      molecules. In this work, a series of Backbone Cyclic Peptide (BCP) analogs that
      bear a conformationally constrained arginine rich motif (ARM) of Rev were tested
      for in vitro inhibition of HIV-1 replication. We observed a potent suppression of
      HIV-1 replication in chronically infected T lymphocytic cells treated with Rev
      BCPs. We further investigated possible mechanisms of HIV-1 inhibition and showed
      that Rev-BCPs interfere slightly with the nuclear import process and are very
      efficient in blocking a mechanism that controls Pr55(gag) and gp160(env)
      synthesis. Interestingly, these protein precursors are known to be encoded by
      mRNAs that require Rev-binding for nuclear export. In situ hybridization using a
      Cy-3 conjugated HIV-1 gag oligonucleotide probe indicated that Rev-BCPs prevent
      the intracellular accumulation of unspliced viral RNA. As a model, the most
      promising analog, Rev-BCP 14, was studied by molecular modeling and dynamics in
      order to identify its binding site on the Rev Response Element (RRE). The
      annealing simulation suggests that upon binding on the RRE, Rev-BCP 14 widens the
      distorted major groove of the viral RNA. Numerous contacts between peptide and
      RNA were found within the complex and some were identified as key components for
      the interactions. Altogether, our data indicate that the use of conformationally
      constrained Rev-BCPs represents a promising strategy for the development of new
      peptide-based therapeutic agents against HIV-1.

PMID- 17520356
TI  - Randomized controlled trial of workplace-based rehabilitation for work-related
      rotator cuff disorder.
AB  - INTRODUCTION: Return to work following an occupational injury is a multifactoral
      process although many traditional clinic-based rehabilitation programs do not
      appreciate the importance of workplace factors. A randomized controlled trial was
      conducted to investigate the effect of workplace-based rehabilitation program on
      the return to work outcome of work-related rotator cuff disorder, which is based
      on the therapeutic use of actual work facilities and work environment. METHODS: A
      total of 103 workers were recruited and randomly assigned into Clinic-based Work
      Hardening (CWH) or Workplace-based Work Hardening (WWH) groups. The CWH group
      were given traditional generic work hardening training while WWH group received
      workplace-based work hardening training with rehabilitative principles of
      athletic rotator cuff pathology, biomechanics and specific job activities.
      RESULTS: After four weeks, a higher return to work rate was obtained in WWH group
      compared to CWH group (71.4% vs. 37%, p < 0.01). A statistically significant
      difference (p < 0.05) was also noted in lowering of self-reported shoulder
      problems and functional work capabilities in the WWH group versus the CWH group.
      CONCLUSION: Workplace-based rehabilitation program appeared to be more effective
      in facilitating the return to work process of the injured worker as assessed
      immediately following intervention. In particular this approached was associated
      with many of the psychosocial workplace factors related to separation from the
      work routine. The influence of peer group and/or employer could be minimized.
      This initial attempt with rotator cuff injuries appears promising however long
      term outcome needs to be determined.

PMID- 17520357
TI  - Is phosphorescence lifetime an indicator of angiogenesis in cortical sarcoma?
AB  - In this paper, the oxygen dependent phosphorescence quenching method is proposed
      to study the correlation between the phosphorescence lifetime and microvessel
      density in tumors. In the implementation, the S180 transplanted tumor in the
      mouse is used for the collection of the time-resolved phosphorescence, the tumor
      microvessel density is measured by immunohistochemical examination of FVIII, the
      correlation between microvessel density and phosphorescence lifetime is analyzed
      by multiple regression method. The results show the phosphorescence decay
      constant measured in tumors is enlarged in the tumor progression. Furthermore,
      the relative total microvessel area is positively correlative with the
      phosphorescence lifetime, which is estimated by a two dimension regression
      equation. It is concluded phosphorescence lifetime is a valuable indicator of
      angiogenesis during the tumor development.

PMID- 17520358
TI  - Transcatheter cryoablation with 3-D mapping of an atrial ectopic tachycardia in a
      pediatric patient with tachycardia induced heart failure.
AB  - Atrial ectopic tachycardias (AET) are often resistant to medical management and
      can lead to a significant reduction in cardiac function. Transcatheter
      cryoablation, a definitive therapy, to our knowledge has yet to be described in
      the pediatric population. A three-year-old male presented with AET induced heart
      failure which persisted despite medical management. Management was complicated by
      worsening heart failure and propylene glycol intoxication. He underwent
      transcatheter cryoablation using a 3-D navigation system with an initially
      successful elimination of the arrhythmia. After a late recurrence (15 months) of
      the AET he underwent epicardial transcatheter ablation using cryotherapy with
      successful elimination of the arrhythmia.

PMID- 17520359
TI  - Capture of activation during ventricular arrhythmia using distributed
      stimulation.
AB  - Results of previous studies suggest that pacing strength stimuli can capture
      activation during ventricular arrhythmia locally near pacing sites. The existence
      of spatio-temporal distribution of excitable gap during arrhythmia suggests that
      multiple and timed stimuli delivered over a region may permit capture over larger
      areas. OBJECTIVE OF THE STUDY: Our objective in this study was to evaluate the
      efficacy of using spatially distributed pacing (DP) to capture activation during
      ventricular arrhythmia. METHODS: Data were obtained from rabbit hearts which were
      placed against a lattice of parallel wires through which biphasic pacing stimuli
      were delivered. Electrical activity was recorded optically. Pacing stimuli were
      delivered in sequence through the parallel wires starting with the wire closest
      to the apex and ending with one closest to the base. Inter-stimulus delay was
      based on conduction velocity. Time-frequency analysis of optical signals was used
      to determine variability in activation. A decrease in standard deviation of
      dominant frequencies of activation from a grid of locations that spanned the
      captured area and a concurrence with paced frequency were used as an index of
      capture. RESULTS: Results from five animals showed that the average standard
      deviation decreased from 0.81 Hz during arrhythmia to 0.66 Hz during DP at pacing
      cycle length of 125 ms (p = 0.03) reflecting decreased spatio-temporal
      variability in activation during DP. Results of time-frequency analysis during
      these pacing trials showed agreement between activation and paced frequencies.
      CONCLUSIONS: These results show that spatially distributed and timed stimulation
      can be used to modify and capture activation during ventricular arrhythmia.

PMID- 17520360
TI  - Psychophysiological effects of breathing instructions for stress management.
AB  - Stressed and tense individuals often are recommended to change the way they
      breathe. However, psychophysiological effects of breathing instructions on
      respiration are rarely measured. We tested the immediate effects of short and
      simple breathing instructions in 13 people seeking treatment for panic disorder,
      15 people complaining of daily tension, and 15 controls. Participants underwent a
      3-hour laboratory session during which instructions to direct attention to
      breathing and anti-hyperventilation instructions to breathe more slowly,
      shallowly, or both were given. Respiratory, cardiac, and electrodermal measures
      were recorded. The anti-hyperventilation instructions failed to raise end-tidal
      pCO(2) above initial baseline levels for any of the groups because changes in
      respiratory rate were compensated for by changes in tidal volume and vice versa.
      Paying attention to breathing significantly reduced respiratory rate and
      decreased tidal volume instability compared to the other instructions. Shallow
      breathing made all groups more anxious than did other instructions. Heart rate
      and skin conductance were not differentially affected by instructions. We
      conclude that simple and short instructions to alter breathing do not change
      respiratory or autonomic measures in the direction of relaxation, except for
      attention to breathing, which increases respiratory stability. To understand the
      results of breathing instructions for stress and anxiety management, respiration
      needs to be monitored physiologically.

PMID- 17520361
TI  - Direct and passive prenatal nicotine exposure and the development of
      externalizing psychopathology.
AB  - The association between maternal smoking during pregnancy and childhood
      antisocial outcomes has been demonstrated repeatedly across a variety of
      outcomes. Yet debate continues as to whether this association reflects a direct
      programming effect of nicotine on fetal brain development, or a phenotypic
      indicator of heritable liability passed from mother to child. In the current
      study, we examine relations between maternal smoking and child behavior among 133
      women and their 7-15-year-olds, who were recruited for clinical levels of
      psychopathology. In order to disentangle correlates of maternal smoking, women
      who smoked during pregnancy were compared with (a) those who did not smoke, and
      (b) those who did not smoke but experienced significant second-hand exposure.
      Second-hand exposure was associated with increased externalizing psychopathology
      in participant mothers' offspring. Moreover, regression analyses indicated that
      smoke exposure during pregnancy predicted conduct disorder symptoms, over and
      above the effects of income, parental antisocial tendencies, prematurity, birth
      weight, and poor parenting practices. This is the first study to extend the
      findings of externalizing vulnerability to second hand smoke exposure.

PMID- 17520362
TI  - Postconditioning: a mechanical maneuver that triggers biological and molecular
      cardioprotective responses to reperfusion.
AB  - Infarct size is determined not only by the duration and severity of ischemia, but
      also by pathological processes initiated at reperfusion (reperfusion injury).
      Numerous pharmacological strategies have been reported which administer drugs at
      or just before the onset of reperfusion, with subsequent salubrious effects,
      notably a reduction in infarct size. However, few if any of these strategies have
      become standard of care in the catheterization laboratory setting.
      Postconditioning, defined as repeated brief cycles of reperfusion interrupted by
      ischemia (or hypoxia) applied at the onset of reperfusion, was recently
      introduced as a mechanical strategy to attenuate reperfusion injury.
      Postconditioning intervenes only during the first few minutes of reperfusion.
      However, it reduces endothelial activation and dysfunction, the inflammatory
      response to reperfusion, necrosis, and apoptosis both acutely and long-term.
      Cardioprotection has been demonstrated by multiple independent laboratories and
      in multiple species. Postconditioning stimulates G-protein coupled receptors by
      their cognate endogenously released ligands and surprisingly activates survival
      kinases that may converge on mitochondrial K(ATP) channels and the permeability
      transition pore. Postconditioning has been shown in two clinical studies to
      reduce infarct size in patients undergoing percutaneous coronary intervention in
      the catheterization laboratory, and at least five other studies are in some phase
      of implementation. This significant reduction in infarct size has implications
      for reduction in heart failure as a consequence of myocardial infarction, but
      this link has yet to be demonstrated. The salubrious effects of postconditioning
      are an indirect validation of the experimental and clinical importance of
      reperfusion injury in the setting of coronary artery occlusion.

PMID- 17520363
TI  - Na(+)-independent choline transport in rat retinal capillary endothelial cells.
AB  - The purpose of this study was to clarify the mechanism of the inner blood-retinal
      barrier (inner BRB) transport of choline and examine the choline uptake ability
      of rat choline transporter-like protein (CTL) 1. The transcript level of CTL1 in
      a conditionally immortalized rat retinal capillary endothelial cell line (TR
      iBRB2) is more than 100-fold greater than that of CTL3 and CTL4, and no
      expression of organic cation transporter (OCT) mRNA was detected. The apparent
      influx permeability clearance of [(3)H]choline in the rat retina was found to be
      271 microl/(min x g retina). The [(3)H]choline uptake by TR-iBRB2 cells was Na(+)
      independent, potential-dependent, and concentration-dependent with Michaelis
      Menten constants of 6.44 microM and 99.7 microM, and inhibited by several organic
      cations but not tetraethylammonium. The inhibition of CTL1 mRNA by small
      interfering RNA had little effect on the [(3)H]choline uptake by TR-iBRB2 cells.
      Rat CTL1-expressing Xenopus laevis oocytes exhibited an increase in the
      [(3)H]choline uptake by 45% compared with a control. In conclusion, our findings
      are consistent with Na(+)-independent choline transport being the mechanism for
      blood-to-retina transport of choline at the inner BRB. Although rat CTL1
      expression is associated with the choline uptake, CTL1 does not play a major role
      in the choline uptake at the inner BRB.

PMID- 17520364
TI  - Relationship among oxidative DNA damage, gastric mucosal density and the
      relevance of cagA, vacA and iceA genotypes of Helicobacter pylori.
AB  - The aim of this study was to evaluate the relationship among oxidative DNA
      damage, density of Helicobacter pylori and the relevance of cagA, vacA and iceA
      genotypes of H. pylori. Gastric epithelial cells were isolated from 24 uninfected
      patients, 42 H. pylori infected patients with gastritis, and 61 patients with
      gastric cancer. Oxidative DNA damage was analyzed by the Comet assay, the density
      of H. pylori was measured by real-time polymerase chain reaction (PCR), and
      allelic variants of cagA, vacA and iceA were identified using the PCR. Infected
      patients by Helicobacter pylori cagA(+), vacAs1 m1 and iceA1 genotype showed
      higher levels of oxidative DNA damage than infected patients with H. pylori cagA(
      ), vacAs2 m2 and iceA2 genotypes and uninfected patients. Density of H. pylori
      did not influence oxidative DNA damage. Our results indicate that H. pylori
      genotype is more relevant than density for oxidative DNA damage.

PMID- 17520365
TI  - Rifaximin versus other antibiotics in the primary treatment and retreatment of
      bacterial overgrowth in IBS.
AB  - PURPOSE: Previous studies demonstrate improvement in IBS after antibiotic
      therapy, with the greatest efficacy seen with the antibiotic, rifaximin. The
      purpose of this study was to compare the efficacy of rifaximin in both the
      treatment and retreatment of IBS. METHODS: A retrospective chart review was
      conducted on Rome I-positive IBS patients. Charts were reviewed to evaluate all
      antibiotic treatments (rifaximin, neomycin, doxycycline, amoxicillin/clavulanate,
      and ciprofloxacin), even those predating 1 July 2004. Data collection included
      symptoms, breath test results (pre- and post-treatment), antibiotics used, and
      clinical response to individual antibiotic treatments before and after rifaximin
      availability in the USA. RESULTS: Out of 98 eligible charts, 84 patients received
      one course of rifaximin. Fifty of these (60%) had a follow-up breath test. Among
      these, 31 (62%) were clinical responders and 19 (38%) were nonresponders. Of 31
      responders, 25 (81%) had a normal follow-up breath test compared with only 3 of
      the 19 nonresponders (16%) (P < 0.001). Of participants given rifaximin, 69% (58
      out of 84) had a clinical response compared with only 38% (9 out of 24) with
      neomycin (P < 0.01) and 44% (27 out of 61) with all non-rifaximin antibiotics (P
      < 0.01). Rifaximin was used as retreatment on 16 occasions, and all patients
      improved. CONCLUSIONS: Rifaximin is more effective than other antibiotics in the
      treatment and retreatment of IBS.

PMID- 17520366
TI  - Fecal incontinence: a review.
AB  - Fecal incontinence (FI) is defined as the involuntary passage of fecal material
      through the anal canal. True incontinence must be differentiated from pseudo
      incontinence. FI is predominately a disease of the elderly or of institutional
      patients. Fecal incontinence in the nursing home population has been estimated at
      47%. We provide a guide to appropriate clinical evaluation, diagnostic testing,
      and treatment of FI.

PMID- 17520367
TI  - Effect of anastomosis level on continence performance and quality of life after
      colonic J-pouch reconstruction.
AB  - Total mesorectal excision (TME) has become the recommended method for treatment
      of cancer in the middle or lower third of the rectum. Thus very low anastomoses
      are necessary to preserve continence, and pouch reconstruction is favored. It is
      unclear whether the level of anastomosis is important for continence and quality
      of life in colonic J-pouch reconstruction. In this investigation all patients
      were included who underwent curative elective anterior continuity resection with
      colorectal or coloanal J-pouch reconstruction for primary rectal cancer between
      January 2001 and December 2004. Exclusion criteria were distant metastases and
      any signs of recurrence at the time of investigation. Evaluation of continence
      performance by Wexner and Holschneider questionnaire and quality of life using
      the QLQ-C30 and QLQ-CR38 (EORTC) questionnaires was done 220 +/- 38 days after
      closure of the protective Ileostomy, which was performed 106 +/- 48 days after
      primary intervention. Fifty-two patients (79%) were analyzed. Colopouch rectal
      anastomosis was performed in eighteen cases and colopouch anal anastomosis in
      thirty-four cases. Fifty percent of the patients in both groups were continent
      for solid stool. Patients with a colopouch anal anastomosis had a significantly
      higher rate of incontinence for liquid stool, however. They took stool-regulating
      medicine more frequently and complained of fecal soiling and a restricted quality
      of life. Patients with a colopouch anal anastomosis had a significantly lower
      score on the most important points of the QLQ-C30 (emotional functioning, social
      functioning, pain, and quality of life). The same applied to the QLQ-CR38 for
      body image and problems with defecation. The quality of life of patients with a
      colopouch anal anastomosis was still considered acceptable compared with
      reference data for the normal healthy population, however. Both continence and
      quality of life are substantially affected by the level of the anastomosis after
      colonic pouch reconstruction. This suggests preservation of a small part of the
      rectum when oncologically feasible and performing a colopouch rectal anastomosis.

PMID- 17520368
TI  - Mathematical modeling of guided neurite extension in an engineered conduit with
      multiple concentration gradients of nerve growth factor (NGF).
AB  - Neurotrophic factors such as nerve growth factor (NGF) provide essential cues to
      navigate growing axon toward their targets. Concentration and concentration
      gradient of NGF are key parameters affecting the growth rate and direction of
      neurites and axons. However, the maximum distance for guided nerve growth under
      stimulation of a single concentration gradient is limited and is thus unfavorable
      in nerve regeneration. Since the sensitivity of PC12 cells to NGF signals is
      restorable even after brief removal of the factors, exposure to multiple
      concentration gradients of the factor can achieve longer distances and greater
      rates of guided growth. In this study, a mathematical model simulating nerve
      growth in a virtually constructed nerve conduit incorporating multiple NGF
      concentration gradients is established. Using a genetic algorithm, optimized
      initial profiles of NGF able to achieve 4.5 cm of guided growth with a
      significantly improved growth rate has been obtained. The model also predicts an
      inverse relationship between the diffusion coefficient of the factor and the
      neurite growth rate. This model provides a useful tool for evaluating various
      conduit designs before fabrication and evaluation.

PMID- 17520369
TI  - Simulation and experimentation of a microfluidic device based on electrowetting
      on dielectric.
AB  - Electrowetting on dielectric (EWOD) moving fluid by surface tension effects
      offers some advantages, including simplicity of fabrication, control of minute
      volumes, rapid mixing, low cost and others. This work presents a numerical model
      using a commercial software, CFD-ACE+, and an EWOD system including a
      microfluidic device, a microprocessor, electric circuits, a LCD module, a keypad,
      a power supply and a power amplifier. The EWOD model based on a reduced form of
      the mass conservation and momentum equations is adopted to simulate the fluid
      dynamics of the droplets. The EWOD device consists of the 2 x 2 mm bottom
      electrodes (Au/Cr), a dielectric layer of 3,000 A nitride, 500 A Teflon and a
      piece of indium tin oxide (ITO)-coated glass as the top electrode. The complete
      EWOD phenomenon is elucidated by comparing simulation with the experimental data
      on droplet transportation, cutting and creation. In transportation testing, the
      speed of the droplet is 6 mm/s at 40 V(dc). In addition, the droplet division
      process takes 0.12 s at 60 V(dc) in the current case. Finally, a 347 nl droplet
      is successfully created from an on-chip reservoir at 60 V(dc).

PMID- 17520370
TI  - A flexible and wearable biosensor for tear glucose measurement.
AB  - A flexible and wearable amperometoric glucose sensor was fabricated and tested.
      Also, the sensor was utilized to tear glucose monitoring. The sensor was
      constructed by immobilizing GOD onto a flexible oxygen electrode (Pt working
      electrode and Ag/AgCl counter/reference electrode), which was fabricated using
      "Soft-MEMS" techniques onto a functional polymer membrane. In purpose of
      bioinstrumentation, adhesive agents were not used for constructing the flexible
      biosensor. Linear relationship between glucose concentration and output current
      was obtained in a range of 0.025-1.475 mmol/l, with a correlation coefficient of
      0.998. Current dependences on pH and temperature were also evaluated. The current
      was largest at pH 7.0 and the current increased when temperature increased. This
      indicates that the output current depends on enzyme activity. Based on the basic
      characteristics investigation, the glucose sensor was applied to measurement of
      glucose in tear fluids on an eye site of a Japan white rabbit. The change of tear
      glucose level induced by oral-administration of glucose was monitored as a
      current change of the sensor attached on the eye site. In this investigation, the
      tear glucose level varied from 0.16 to 0.46 mmol/l. Although there was a delay of
      several tens of minutes towards blood sugar level, it is considered to be
      possible that non-invasive continuous glucose monitoring can be realized using
      the flexible biosensor.

PMID- 17520371
TI  - A model neural interface based on functional chemical stimulation.
AB  - While functional electrical stimulation has been applied to treat a variety of
      neurological disorders, it cannot mimic function that is primarily achieved using
      neurochemical means. In this work, we present a neurotransmitter-based prosthetic
      interface in the form of a flexible microdevice that selectively releases
      chemical pulses through an aperture in a polymer membrane. The release profiles
      through the aperture are controlled by microfluidic switching in an underlying
      channel network. The profiles have been characterized using fluorescence
      microscopy as a function of pulse duration and frequency. Hippocampal neurons
      were cultured on the microdevices and cell stimulation via glutamate delivery was
      detected using calcium imaging. The release properties could be tuned to
      repeatedly elicit discrete action potentials in cells seeded proximate to the
      aperture, including single cell stimulation at 2 Hz. This model neural interface
      based on functional chemical stimulation may provide the biomimetic platform
      necessary to restore physiological pathways and function that electrical
      stimulation cannot fundamentally address.

PMID- 17520372
TI  - Analysis of pH and electrically controlled swelling of hydrogel-based micro
      sensors/actuators.
AB  - In this paper, we carry out the theoretical electro-chemo-mechanical
      investigation into water swollen ionic polymer gels under the simultaneous
      influence of electrical and chemical stimuli. In addition to these hydrogels
      being deployed as active sensing/actuating elements in MEMS/BioMEMS devices, this
      work can also serve as the basis of illustrating synthetic analogs of
      physiological muscles with possible applications in orthotics, prosthetics, and
      as artificial muscles. An electro-chemo-mechanical model or Multi-Effect-Coupling
      of pH Stimulus (MECpH) model, which was developed earlier by the present authors,
      is significantly extended to handle nonlinear deformation and implemented
      numerically to simulate the deformation characteristics of the pH-stimulus
      responsive hydrogel under the application of an externally applied voltage in
      different buffered pH solutions. The nonlinear deformation theory provides more
      accurate results especially when the deformations are large. The hydrogel is
      observed to experience swelling and bending when pH and external electric field
      stimuli coexist. The mode and degree of deformation are found to be highly
      dependent on changes of environmental pH, external electrical potential and
      bathing ionic strength. As an anionic hydrogel is considered in the simulation,
      it shows larger changes in deformation characteristic in basic than in acidic
      solutions. More importantly, the average curvatures of the swollen hydrogel are
      found to be a linear function with the applied electric potential, making the
      hydrogel an ideal actuator. However, we also note a significant decrease in the
      swelling equilibrium degree as the ionic strength becomes concentrated.

PMID- 17520373
TI  - The sustainability of systems of care for children's mental health: lessons
      learned.
AB  - The federal Comprehensive Community Mental Health Services for Children and Their
      Families Program was initiated in 1992 to provide grants to states, communities,
      territories, and Indian tribes to develop systems of care to serve children and
      adolescents with or at risk for emotional disorders and their families. As part
      of the national evaluation of this program, a study was undertaken to assess the
      ability of funded sites to sustain their systems of care beyond the federal grant
      period. The study involved a web survey and telephone interviews with local and
      state respondents to examine the extent to which key components of systems of
      care were maintained during the period in which federal funds were phasing out
      and during the post grant period. Study results demonstrate positive and negative
      changes that occurred in the communities which are included in the sample, with
      respect to maintaining the availability of each service included in the broad
      service array, the implementation of system of care principles, the system of
      care infrastructure, and the achievement of system of care goals. In addition,
      results identify factors that contribute to or impede the ability to sustain
      systems of care, and the effectiveness of various strategies for sustainability.
      Study findings offer guidance not only to federally funded system of care
      communities but also to non-funded communities engaged in system of care
      development to enhance their ability to sustain systems of care for this
      population over time. Findings will also assist federal, state, and local
      policymakers, technical assistance providers, family members, advocates, and
      other key stakeholders to more effectively support the development of viable,
      sustainable systems of care.

PMID- 17520374
TI  - [Clinical characteristics and surgical treatment of Crohn disease complicated
      with intra-abdominal abscess].
AB  - OBJECTIVE: To elucidate the clinical characteristics and surgical treatment of
      intra-abdominal abscess in patients with Crohn disease(CD). METHODS: Clinical
      data of 39 patients with CD complicated with intra-abdominal abscess from 2000 to
      2005 were analyzed retrospectively. RESULTS: The cumulative incidence of intra
      abdominal abscesses was 27.5%. Of the 39 CD patients with abscess, 61.5% had
      surgery the time of present study. The mean age of the patients with abscesses
      was (34.7+/- 12.3) years, and the duration of illness from the onset of CD until
      development of an abscess was (0-22) years,with 5 years of the average duration.
      In terms of location of abscess, it occurred most often on the right side
      (76.9%), especially near the site of anastomosis (48.7%). Most patients (34
      cases, 94.4%) were treated with surgical drainage and intestinal resection.
      CONCLUSIONS: Abscess formation was noted in 27.5% of patients with CD, with
      nearly half of abscesses occurring near the anastomotic site. The mean age of
      patients with abscess was 35 years, with 5 years of the duration of illness. Most
      abscesses were treated with operative drainage and intestinal resection.

PMID- 17520375
TI  - [Risk factors of operation and reoperation in patients with Crohn disease].
AB  - OBJECTIVE: To explore the operative rate and reoperative rate of Crohn
      disease(CD) in China, and to assess the relative risk factors indicating surgical
      treatment in CD patients. METHODS: Data of initial operation and reoperation were
      evaluated retrospectively in a cohort of 142 patients with CD. The influence of
      concomitant risk factors was assessed using multivariate analyses. RESULTS: Of
      the 142 cases of CD patients, 64.8% required at least one operation and the
      cumulative rate of operation was 52% at 5 years after onset. The relative risk of
      operation was increased in male patients, older than 40 years of age at onset,
      and those with CD involving small bowel. Of the patients undergone operation,
      33.9% relapsed and required reoperation subsequently. The cumulative reoperation
      rate was 21% at 3 years after first operation. Male gender, a perforating
      indication for initial operation, as well as colonic and ileocolonic disease,
      increased the relative risks of reoperation. CONCLUSIONS: Half of patients with
      CD will undergo an operation at 5 years after onset, and 20% of them will relapse
      and require reoperation at 3 years after first operation. Men run a higher risk
      of operation and reoperation than women do. A perforating indication for initial
      operation predict a higher risk of reoperation.

PMID- 17520376
TI  - [Experimental study of the hepatocyte growth factor contributing to
      lymphangiogenesis and lymphatic metastasis in gastric cancer].
AB  - OBJECTIVE: To investigate relationship between the expression of hepatocyte
      growth factor(HGF) and lymphatic vessel formation in gastric cancer(GC), and to
      further clarify the possible ways of HGF promoting GC lymphangiogenesis and
      lymphatic metastasis. METHODS: The expression of HGF, VEGF-C, c-Met and
      microlymphatic density(MLD) in tumor and non-tumor areas of 60 cases of GC and 20
      cases of peptic ulcer (PU) were evaluated by immunohistochemistry. The
      relationships between MLD and clinicopathologic features of GC were analyzed.
      RESULTS: The proteins of HGF, VEGF-C, and c-Met were overexpressed in GC tissues,
      which were significantly higher than those in normal gastric and PU tissues
      (P<0.001). The MLD of GC was also significant higher than those of normal gastric
      tissue and PU tissues (P<0.05). C-Met was expressed on enlarge lymphatic vessels
      in GC and PU tissues. MLD was positively correlated with the expression of HGF in
      GC (P<0.001). CONCLUSION: HGF as well as VEGF-C is a lymphangiogenic factor in
      GC. HGF can directly or indirectly stimulate lymphangiogenesis and contribute to
      lymphatic metastasis in GC.

PMID- 17520377
TI  - [Detection of microsatellite instability in colorectal cancer by fluorescence
      multiplex polymerase chain reaction and its clinical value].
AB  - OBJECTIVE: To detect microsatellite instability(MSI) in colorectal cancer by
      fluorescence multiplex polymerase chain reaction(FM-PCR) and explore its clinical
      value. METHODS: MSI of 110 colorectal cancer patients undergone surgical
      resection in our department from 2004 to 2005 were examined by FM-PCR, and the
      pathological characteristics were compared between MSI and microsatellite stable
      (MSS) colorectal cancer patients. RESULTS: Among 110 cases, the male were 66 and
      the female were 44. Mean age was 60.8 (26-94) yrs. All 5 microsatellite markers
      were amplified. Out of them, 10 cases (8.1%) were MSI-H, 13 cases (11.8%) were
      MSI-L and 87 cases (79.1%) were MSS. Instability of BAT-26 was found in 9 cases
      (8.2%), BAT-25 was in 11 cases (10.0%), D2S123 was in 11 cases (10.0%), D5S346
      was in 6 cases (8.2%) and D17S250 was in 8 cases (7.3%). Age between MSI and MSS
      colorectal cancer patients was significant and other pathological characteristics
      were not significant. CONCLUSIONS: FM-PCR is a clinically stable method for MSI
      detection in colorectal cancer patients. There are no significant differences
      between MSI and MSS pathological characteristics of colorectal cancer patients.

PMID- 17520378
TI  - [Retrospective analysis of extended gastrectomy and lymphadenectomy in early
      gastric cancer patients].
AB  - OBJECTIVE: To objectively evaluate the practical significance of different
      extended surgeries in early gastric cancer(EGC) patients, and to choose
      reasonable gastrectomies and lymphadenectomies. METHODS: A total of 217 EGC
      patients were investigated undergone normalized D2 or above extended surgery and
      their clinicopathological data were recorded in detail. The efficiency of the
      extended lymphadenectomies, complications and operation causes were analyzed, and
      the correlation between the group 2 lymph node metastasis (LNM) and
      clinicopathological factors were assessed, too. RESULTS: There was no nodal
      involvement in the No.5 and No.6 lymph nodes among the total gastrectomy in the
      upper third of the stomach, neither was in the No.10, 11p and 11d lymph nodes
      among the combined splenectomy, and neither was in the No.15 lymph nodes among
      the combined transverse mesocolon resection in the lower third of the stomach.
      There was no distant nodal involvement in the EGC. Above all, most of them were
      mistaken for advanced gastric cancer preoperatively and intraoperatively, the
      operation time was longer and the blood loss was more during operation. Among the
      resected nodes of group 2 in the lower third of the stomach, metastasis was not
      found in the No.11p, 12a and 14v lymph nodes. The rate of the No.7 and 8a nodal
      involvement in the submucosa cancer was higher than that in the mucosa
      cancer(P<0.05) and so did the No.7 in the lymphatic penetration
      positive(P<0.001). The No.1 and No.13 nodal involvement were only seen in the
      high risk cases, such as submucosa cancer, the lesion diameter more than 3.0 cm,
      depressed type and lymphatic involvement. CONCLUSION: It is not necessary to
      execute total gastrectomy in the upper third of the stomach, combined organ
      resection (such as splenectomy, transverse mesocolon resection), and distant
      lymph node dissection in the EGC. In the lower third of the stomach, the No.11p
      12a and 14v lymph nodes shouldn't be dissected. With respect to the high risk
      nodal involvement cases in the lower third of the stomach, the No.1 lymph nodes
      should be dissected and so does the No.13 lymph nodes if it's tumefied. It is the
      key point of reasonable operation to exactly diagnose the EGC before and during
      the surgery.

PMID- 17520379
TI  - [Reevaluation resection margin rectal cancer by flow cytometry and pathological
      examination].
AB  - OBJECTIVE: To investigate the appropriate distal resection margin in rectal
      cancer patients. METHODS: Thirty specimens of rectal carcinoma with total
      mesorectal excision(TME) were studied by flow cytometry and pathological
      examination. The differences of DNA ploidy status, DNA index (DI), proliferative
      index (PI), S-phase fraction (SPF) among rectal cancer, 3 cm and 5 cm below the
      tumor, normal rectum, distal mesorectum 3 cm and 5 cm below the tumor, and normal
      colon mesentery were analysed by flow cytometry, and were compared with the data
      of pathological examination. RESULTS: Pathological examination showed that there
      was no tumor invasion 3 cm and 5 cm below the tumor,but the metastasis rates of
      distal mesorectum 3 cm and 5 cm below the tumor were 26.7% and 6.7% respectively.
      The DI, PI and SPF of rectal cancer by flow cytometric examination were
      significantly higher than those of distal rectum 3 cm and 5 cm below the tumor,
      and normal rectum (P<0.05). The DI, PI and SPF of distal rectum 3 cm below the
      tumor were also significantly higher than those of distal rectum 5 cm below the
      tumor, and normal rectum (P<0.05), but there were no significant differences
      between DI, PI and SPF of distal rectum 5 cm below the tumor and those of normal
      rectum (P>0.05). The rate of DNA aneuploid of tumor was significantly higher than
      those of normal rectum and distal rectum 5 cm below the tumor,but there was no
      significant difference between the rate of DNA aneuploid of tumor and that of
      distal rectum 3 cm below the tumor. The DI and DNA aneuploid of rectal cancer and
      distal mesorectum 3 cm and 5 cm below the tumor were significantly higher than
      those of normal mesorectum,but there were no significant differences between DI
      and DNA aneuploid of rectal cancer and those of distal mesorectum 3 cm and 5 cm
      below the tumor. The PI and SPF of rectal cancer were significantly higher than
      those of normal mesorectum and distal mesorectum 3 cm and 5 cm below the tumor.
      CONCLUSIONS: Rectal cancer is able to invade distal rectum 3 cm below the tumor
      and distal mesorectum 5 cm below the tumor, and radical resection of rectal
      cancer should beyond that range.

PMID- 17520380
TI  - [Computer tomography appearances of the enterocutaneous fistula classification].
AB  - OBJECTIVE: To discuss the computer tomography(CT) appearances of the
      enterocutaneous fistula classification. METHODS: CT scan was performed on 754
      patients with enterocutaneous fistula, which were divided into tube fistula and
      labiate fistula according to clinic classification, and the appearances of CT
      scan were analyzed respectively. RESULTS: Five hundreds and eighteen patients
      (68.6%) were diagnosed as tube fistula, and CT appearance of which was a duct
      formed between internal hole and external hole. Two hundreds and thirty-six
      patients (31.4%) were diagnosed as labiate fistula,and CT appearance of which was
      a large external hole like labium.The basic appearance of intestine and celiac
      cavity in enterocutaneous fistula was inflammatory focus. The incidence of
      abscesses in tube fistula was higher than that in labiate fistula (P<0.01). The
      intestinal inflammation was more common in labiate fistula than that in tube
      fistula (P<0.01). CONCLUSION: There are characteristic CT appearances in
      enterocutaneous fistula and CT scan is useful for classification of
      enterocutaneous fistula.

PMID- 17520381
TI  - [Effect of surgical manipulation on the dissemination of cancer cells into
      peripheral blood in patients with gastric cancer and its risk factor analysis].
AB  - OBJECTIVE: To evaluate the effect of surgical manipulation on the dissemination
      of cancer cells into blood circulation in patients with gastric cancer and to
      analyze its risk factors. METHODS: This study included 45 consecutive patients
      with gastric cancer undergoing curative resection and 13 control cases (10
      healthy persons and 3 patients with peptic ulcer receiving gastrectomy).
      Peripheral blood was obtained preoperatively and just after surgical
      manipulation. The mRNA levels of carcinoembryonic antigen (CEA) from the blood
      samples were assayed by reverse transcription-polymerase chain reaction(RT-PCR)
      and compared between the 2 groups. RESULTS: CEA mRNA was negative in all control
      cases. Of the 45 gastric cancer patients, the preoperative positive rate of CEA
      mRNA was 8.9%, while the postoperative positive rate was 48.9%, which was
      significantly higher than that of preoperation (P=0.000). Multivariable Logistic
      regression analysis showed that operative duration (P=0.014) and tumor depth
      (P=0.010) were independent risk factors for cancer cell dissemination.
      Furthermore, the operative duration in patients with positive postoperative CEA
      mRNA was markedly longer than that in patients with negative postoperative CEA
      mRNA (P=0.000), and positive rate of postoperative CEA mRNA in advanced gastric
      cancer was higher compared with that in early gastric cancer (P=0.034).
      CONCLUSIONS: Surgical manipulation of curative gastrectomy can provoke
      dissemination of cancer cells into blood circulation, and the operative duration
      and tumor invasion depth may be 2 of the risk factors for cancer cell
      dissemination.

PMID- 17520382
TI  - [Application of the protocol of enhanced recovery after surgery in colorectal
      surgery].
AB  - OBJECTIVE: To evaluate enhanced recovery after surgery(ERAS) protocol in
      colorectal surgery. METHODS: From september 2006 to February 2007, 74 patients
      with colorectal cancer were randomly assigned to ERAS group and control group.
      The stress index, nutrition and metabolism index, intraoperative index and
      postoperative index were evaluated. RESULTS: Six patients were excluded, 3 in
      ERAS group (2 cases received hepatectomy concomitantly and 1 case received
      partial ileum resection), and 3 in control group (1 case received hepatectomy and
      1 case received colorectomy concomitantly, another presented asthma paroxysm). So
      there were 34 cases in ERAS group and 34 cases in control, with no statistical
      differences in sex, age, BMI index and operation types. Deviation of HOMA-IR
      index of ERAS was lower than the control (P>0.05), the same as plasma cortisol at
      the 1st day after operation (P<0.05), but plasma glucagons in the operation of
      ERAS group was higher than that of control (P<0.05). Plasma glucose 1st day after
      operation of ERAS group was lower than control (P<0.05), while plasma
      triglyceride intraoperation, at 1st day, 2nd day after operation of ERAS was
      higher than control (P<0.05). Nitrogen negative balance of ERAS group was higher
      than control at 2nd day after surgery, but is lower intraoperation and at 6th day
      after operation (P<0.05). The time of exhaust gas and stool, time to eat fluidity
      and semi-fluidity, out-of-bed time and exercise time per-day, residual time and
      complication rate in ERAS group were better than those of control (P<0.05). Post
      operative expenses of ERAS was lower than that of control (P<0.05). CONCLUSION:
      ERAS can decrease surgical stress, increase functional recovery and reduce
      complication rate.

PMID- 17520383
TI  - [Clinical characteristics, diagnosis and treatment of hepatoid adenocarcinoma of
      the stomach].
AB  - OBJECTIVE: To investigate the clinical characteristics,diagnosis and treatment of
      hepatoid adenocarcinoma of the stomach. METHODS: Clinical data of 13 hepatoid
      adenocarcinomas of the stomach, collected from 201 cases of gastric cancer, were
      analyzed retrospectively. RESULTS: Of the 201 gastric carcinomas, there were 13
      AFP-producing adenocarcinomas of the stomach, the positive rate was 6.5%.
      Morphologically, the tumor cells formed glandular, medullary and linear
      structures. Of the 13 hepatoid adenocarcinomas of the stomach, 10 cases were in
      gastric antrum and 10 cases were poorly differentiated. The metastasis rates of
      liver and lymph node in hepatoid adenocarcinoma of stomach were higher than those
      in non-hepatoid adenocarcinoma of stomach. The treatment of hepatoid
      adenocarcinoma of stomach depended mainly on radical resection, and adjuvant
      chemotherapy was needed.The prognosis of hepatoid adenocarcinoma of stomach was
      poor. CONCLUSION: Hepatoid adenocarcinoma of the stomach has its own special
      tumor biological behavior and poor prognosis. Special attention should be paid to
      this disease.

PMID- 17520384
TI  - [Primary non-Hodgkin lymphoma of small bowel: a clinical analysis of 34 cases].
AB  - OBJECTIVE: To study the clinical characteristics,treatment and prognosis of
      primary non-Hodgkin's lymphoma of small bowel. METHODS: The records of 34
      patients with a confirmed diagnosis of primary non-Hodgkin's lymphoma of small
      bowel, registered between Jan. 1996 and Dec. 2005 at our hospital, were retrieved
      and analysed retrospectively. RESULTS: Twenty-seven patients had B-cell lymphoma
      and 7 had T-cell lymphoma of the small bowel. The major symptoms included
      abdominal pain and intestinal obstruction. According to Ann Arbor staging
      classification, 22 patients belonged to stage I~II, including 20 cases of B-cell
      lymphoma and 2 cases of T-cell lymphoma, and 12 patients belonged to stage
      III~IV, including 7 cases of B-cell lymphoma and 5 cases of T-cell lymphoma.
      Compared with T-cell lymphoma patients, B-cell lymphoma patients had lower
      lymphoma stages (P<0.05). Twenty-seven patients were treated with surgical
      resection. Fourteen patients were treated with six cycles of cyclophosphamide,
      doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy, and 8 patients
      were treated with Rituximab at the same time. T-cell lymphoma patients were more
      often treated with emergent operation than B-cell lymphoma patients would
      (P<0.05). It happened more frequently that B-cell lymphoma patients reached
      complete remission and their accumulative survival rate was longer than T-cell
      lymphoma patients did (P<0.05). CONCLUSION: Patients with stages I and II B-cell
      lymphoma of small bowel respond well to surgery and chemotherapy, and the
      treatment and prognosis of patients with T-cell lymphoma of small bowel are
      unsatisfactory.

PMID- 17520385
TI  - [Laparoscopic abdominoperineal resection for low rectal cancer].
AB  - OBJECTIVE: To assess the advantage and disadvantage of laparoscopic abdomino
      perineal resection and open abdominoperineal resection for low rectal cancer.
      METHODS: Patients with low rectal cancer, collected from July 2003 to April 2006,
      were randomly divided into laparoscopic abdominoperineal resection group (37
      cases) and open abdominoperineal resection group (37 cases). Operation time,
      number of lymph node removed, intra-operative blood loss, time to pass flatus,
      time to ambulate, time to discharge, complications, early recurrence, and
      economical cost were compared between the 2 groups. RESULTS: All patients were
      performed successfully. For the first 10 patients, operation time of laparoscopic
      group was significantly longer than that of open group, but there was no
      significant difference between the 2 groups. Intra-operative blood loss of
      laparoscopic group was significantly less than that of open group, but it was
      reverse for the first 10 patients. There was no significant difference in time to
      pass flatus between the 2 groups. Time to ambulate in laparoscopic group was
      significantly earlier than that in open group. There was no significant
      difference in time to discharge between the 2 groups, but it was earlier for
      perineum closure in laparoscopic group. Relative complications of laparoscopic
      group, including pulmonary infection, abdominal wound infection or split, were
      significantly less than those of open group. There was no significant difference
      in number of lymph nodes removed, early recurrence between the 2 groups.
      Operation cost of laparoscopic group was significantly higher than that of open
      group, but there was no significant difference. CONCLUSION: Advantages of
      laparoscopic abdominoperineal resection were characterized for not only minimal
      invasion and good cosmetic outcome but also less blood loss, complications, and
      earlier postoperative recovery. The operation time, total costs and oncological
      clearance of laparoscopic abdominoperineal resection patients were comparable
      with those of open procedure patients.

PMID- 17520386
TI  - [Rule of lymph node metastasis in colorectal cancer and its affecting factors].
AB  - OBJECTIVE: To investigate the rule of lymph node metastasis in colorectal cancer
      and its affecting factors, and to provide clues for clinical diagnosis and
      treatment of colorectal cancer patients. METHODS: The clinical data of 1166 cases
      of colorectal cancer receiving surgical resection were analyzed
      retrospectively.The relationships between clinicopathologic variables and lymph
      node metastases were evaluated by crosstabs and logistic regression in SPSS 10.0
      for windows. RESULTS: The rate of lymph node metastasis in colorectal cancer was
      49.7%. After entering crosstabs estimation, gender and tumor site were not
      significantly correlated with lymph node metastasis in colorectal
      cancer(chi2=1.46, r=0.035, P>0.05 and chi2=3.86, r=0.012, P>0.05). Age, tumor
      size, the massive type of the tumor, the differentiating degree of the tumor,
      histology type and the depth of tumor invasion were proved to be independent
      factors influencing the lymph node metastasis in colorectal cancer (chi2 =13.1,
      r=0.064, P<0.05 and chi2=77.161, r=0.245, P<0.01 and chi2=144.831, r=0.341,
      P<0.01 and chi2=128.310, r=0.318, P<0.01 and chi2=120.418, r=0.319, P<0.01 and
      chi2=227.287, r=0.434, P<0.01). After entering logistic regression estimation,
      the correlativity of risk factor of lymph node metastasis in colorectal cancer:
      the depth of tumor invasion > the massive type of the tumor>the differentiating
      degree of the tumor > tumor size. Preoperative blood serum CEA level was
      significantly correlated with lymph node metastasis (chi2=509.599, r=0.661,
      P<0.01). CONCLUSION: The depth of tumor invasion is the most risk factor of lymph
      node metastasis in colorectal cancer. Preoperative high level of blood serum CEA
      indicates the occurrence of lymph node metastasis.

PMID- 17520387
TI  - [Diagnosis and surgical treatment of abdominal cocoon: a report of 16 cases].
AB  - OBJECTIVE: To explore the diagnosis and surgical treatment of abdominal cocoon.
      METHODS: The clinical data of 16 patients with abdominal cocoon admitted to our
      hospital between Jun. 1993 and Oct. 2006 were analyzed retrospectively. RESULTS:
      Preoperatively, Barium meal X-rays revealed coils of intestine in 8 cases,
      incomplete intestinal obstruction in 6 cases, and prolonged intestinal transit
      time in 2 cases. CT scan showed dilated intestine and intestinal loops seemed to
      be encapsulated in a thickened capsule. After opening the peritoneum, entire or
      partial intestine encapsulated in thickened membrane encasing were found,
      including partial intestine encapsulated in 1 cases(Type I), entire intestine
      encapsulated in 2 cases (Type II), and entire intestine and other organs
      encapsulated in 12 cases(Type III). All the cases underwent adhesiolysis.
      Intestinal splint was done in 2 patients, gastrostomy in one patient with chronic
      pyloric obstruction, radical resection of rectal cancer in one patients and
      ileocolic resection in one patients with Crohn's disease. All patients were
      healed by surgical operation and confirmed the diagnosis histopathologically.
      CONCLUSIONS: Abdominal cocoon is rare. It is difficult to make a right diagnosis
      preoperatively. Barium meal X-rays and CT scan are useful methods for its
      diagnosis. For the treatment, attention should be paid on complete resection of
      fibrous membrane, adhesiolysis and prevent intestinal obstruction.

PMID- 17520388
TI  - [Expression of Plexin A1 in gastric carcinoma and its relationship with tumor
      angiogenesis and proliferation].
AB  - OBJECTIVE: To investigate the expression of Plexin A1 in gastric cancer(GC) and
      its relationship with angiogenesis and proliferation of GC. METHODS: Plexin A1
      mRNA expression in 20 cases of GC specimens and matched resected normal gastric
      tissue were examined by RT-PCR. Plexin A1, Ki-67, vascular endothelial growth
      factor(VEGF) protein expression and microvessel density (MVD) in 50 cases of GC
      specimens and 20 cases of normal gastric mucosa were detected by
      immunohistochemistry. RESULTS: RT-PCR showed that the expression of Plexin A1 in
      GC was significantly higher than that in normal gastric mucosa(0.71 +/- 0.37 vs
      0.60 +/- 0.25, P < 0.05). MVD within tumor tissue increased significantly with
      Plexin A1 mRNA expression(r=0.8736, P < 0.01) and Plexin A1 protein expression (P
      < 0.01). The Plexin A1 expression was positively correlated with the
      proliferation index (Ki-67) of cancer cells (r=0.4851, P < 0.01). However, the
      Plexin A1 expression level had no relationship with the VEGF expression level.
      CONCLUSION: Plexin A1 plays an important role in the occurrence and development
      of GC. Plexin A1 may regulate angiogenesis, and promote the proliferation of GC
      cells.

PMID- 17520389
TI  - [In situ hybridization study on the expression of Kiss-1 and KAI-1 metastasis
      suppressor genes in gastric cancer].
AB  - OBJECTIVE: To investigate the mRNA levels of Kiss-1 and KAI-1 metastasis
      suppressor genes in gastric cancer, and to explore its clinical value. METHODS:
      In situ hybridization was used on routinely paraffin-embedded sections of
      resected specimens of 49 cases with gastric cancer and 20 cases with
      pericancerous tissue. RESULTS: The positive rates and the scores of Kiss-1 and
      KAI-1 mRNA in gastric cancer tissue were significantly lower than those in
      pericancerous tissue (P<0.01). The positive rates and scores in normal to mild
      atypical hyperplasia cases were significantly higher than those in middle to
      severe-atypical hyperplasia of pericancerous tissue (P<0.05,P<0.01). The positive
      rates and scores of Kiss-1 and KAI-1 mRNA in patients with infiltrating depth
      T1~T2, without lymph node metastasis, with only first group of lymph node
      metastasis, and without distant organ metastasis were significantly higher than
      those in patients with infiltrating depth T3~T4, with lymph node metastasis, with
      second or third group of lymph node metastasis and with distant organ metastasis.
      A strong positive correlation was found between the expressive scores of Kiss-1
      and KAI-1 mRNA in gastric cancer (r=0.53, P<0.01). CONCLUSION: The expression of
      Kiss-1 and/or KAI-1 mRNA may be important biological markers of reflecting
      invasive and metastatic potential and prognosis in gastric cancer. The assays of
      Kiss-1 and/or KAI-1 mRNA expression level in benign lesions of stomach may have
      important clinical value for the protection and early-stage finding of gastric
      cancer.

PMID- 17520392
TI  - An important Finnish contribution to the advancement of women's reproductive
      health.
AB  - This issue of Acta Obstetricia Gynecologica Scandinavica contains new guidelines
      for the management of menorrhagia recommended by the Finnish Society of
      Obstetrics and Gynecology. The treatment of menorrhagia has undergone radical
      changes over the last 2 decades, and several new treatment techniques for the
      management of this common and troublesome condition have been introduced. It is
      perhaps particularly appropriate that these guidelines come from Finland, where
      one of the most important advances regarding the modern management of menorrhagia
      has its origin.

PMID- 17520390
TI  - [Effects of anti-angiopoietin-2 antibody on vascularization of an implanted model
      of human colonic carcinoma on chick embryo].
AB  - OBJECTIVE: To establish an implanted model of human colonic carcinoma on chick
      embryo, and to study the effects of anti-angiopoietin-2 antibody on its
      vascularization. METHODS: The human colonic adenocarcinoma cell line HT-29 was
      transplanted on the chick embryo's chorioallantoic membrane(CAM), and the
      angiogenesis characteristics were observed by stero-microscope, light microscope
      and immunohistochemistry. Furthermore, the effects of anti-angiopoietin-2
      antibody on angiogenesis and tumor growth were also investigated. RESULTS: Three
      to seven days after HT-29 cell line was implanted into CAM, tumors grew rapidly
      and new blood vessels grew toward tumors. Five days after anti-angiopoietin-2
      antibody was given, the number of blood vessels in anti-angiopoietin-2 antibody
      group was significantly down-regulated than that in tumor control group observed
      by stero-microscope (37.2+/-4.6 vs 56.8+/-7.4, P<0.01), but was up-regulated than
      that in normal control group (37.2+/-4.6 vs 9.6+/-2.4, P<0.01). Microvessel
      density(MVD) in anti-angiopoietin-2 antibody group was much lower than that in
      tumor control group by histological examination (9.6+/-2.4 vs 20.2+/-5.8,
      P<0.01). CONCLUSION: Angiopoietin-2 antibody is able to inhibit the angiogenesis
      induced by colorectal cancer cell line HT-29 obviously. The anti-angiopoietin-2
      antibody may be potentially useful for clinical treatment of colonic carcinoma.

PMID- 17520393
TI  - Are clinical symptoms more predictive than laboratory parameters for adverse
      maternal outcome in HELLP syndrome?
AB  - BACKGROUND: To determine the risk factors for adverse maternal outcome among
      women with HELLP syndrome. METHODS: Sixty-one pregnancies with hemolysis,
      elevated liver enzymes and low platelet count (HELLP) syndrome diagnosed
      antenatally were reviewed between 2003 and 2005. Maternal outcomes analyzed
      included eclampsia, abruptio placentae, disseminated intravascular coagulopathy
      (DIC), acute renal failure, need for transfusion of blood products, cesarean
      delivery and maternal death. Risk factors included maternal age, parity,
      gestational age at diagnosis, mean arterial blood pressure, headache, visual
      changes, nausea-vomiting, epigastric pain, blood platelet count (<or=50,000
      versus >50,000 cells/mm3), and peak serum levels of aspartate aminotransferase.
      RESULTS: Eclampsia was present in 52%, abruptio placentae in 11%, and DIC in 8%
      of 61 women with HELLP syndrome. 23% women required transfusion of blood
      products, 15% had acute renal failure, and 73% had cesarean section. Women with
      eclampsia had significantly more headache, nausea-vomiting, visual changes and
      epigastric pain (p<0.05). Transfusion was significantly more frequent among women
      with blood platelet counts <or=50,000 cells/mm3 (33 versus 21%; p<0.05). Women
      with a platelet count <or=50,000 cells/mm3 had a higher rate of DIC compared to
      women with a platelet count >50,000 cells/mm3 (33.3 versus 3.8%; p<0.05). In
      women with acute renal failure and abruptio placentae, there were no significant
      differences in all the variables studied between those with and without these
      complications. CONCLUSIONS: Clinical symptoms, such as headache, visual changes,
      epigastric pain and nausea-vomiting, are more predictive than laboratory
      parameters for adverse maternal outcomes.

PMID- 17520394
TI  - Abnormal fetal growth is associated with gestational diabetes mellitus later in
      life: population-based register study.
AB  - BACKGROUND: Increasing evidence has been collected that intrauterine growth
      restriction is associated with development of type-2 diabetes mellitus in adult
      life. The present study was designed to test the hypothesis that abnormal
      intrauterine growth of female fetuses correlates with their future risk of
      developing gestational diabetes mellitus (GDM). METHODS: Population-based
      register study of the data from the Swedish Medical Birth Registry; perinatal
      data from 1973 to 1983 were linked with the diagnosis of GDM during 1987-2001.
      421 women with GDM diagnosis were compared to 60,890 controls with regard to
      maternal age and parity, maternal education (data from the Education Register of
      Statistics Sweden), maternal diagnosis of diabetes, gestational duration, birth
      weight, and gestational age-related birth weight. RESULTS: There was a
      significant association between low (odds ratio (OR): 2.15, 95% confidence
      interval (CI): 1.29-3.50), as well as high (OR: 1.97, 95% CI: 1.12-3.45) birth
      weight and later development of GDM. There was a U-shaped relation between the
      gestational age-related birth weight and risk of developing GDM. A young mother
      and prematurity increased the risk of the offspring developing GDM. Nine of the
      421 women (2.1%) with GDM were born to mothers who had a diagnosis of diabetes.
      The corresponding figures for the controls were 205 of 60,890 (0.3%). CONCLUSION:
      Intrauterine conditions and/or genetic disposition, which affect prenatal growth,
      increase the future risk of the female fetus developing GDM.

PMID- 17520395
TI  - Elective induction of labor: failure to follow guidelines and risk of cesarean
      delivery.
AB  - BACKGROUND: Estimate the frequency of failure to follow the French consensus
      guidelines for elective induction, and assess how failure affects the rate of
      cesarean delivery. METHODS: We compared cesarean rates according to mode of onset
      of labor among 5,046 low-risk patients. Violation of the guidelines was defined
      as induction before 38 weeks or with a Bishop score <5 or with prostaglandins.
      The cesarean risk was analysed with a bivariable and then a multivariable
      analysis, which used a multilevel logistic model. RESULTS: Women with electively
      induced and spontaneous labor had identical cesarean rates (4.1%). The guidelines
      were not followed in 23.2% of elective inductions. The risk of cesarean was
      higher after induction with a Bishop score <5, than after spontaneous labor
      (adjusted OR=4.1, 95% CI [1.3-12.9]), while elective induction with a favourable
      cervix did not increase the cesarean risk. In nulliparas, failure to follow the
      guidelines tripled the risk of cesarean (adjusted OR=3.2 [1.0-10.2]). On the
      other hand, elective induction of labor for women with a favourable cervix did
      not increase the risk of cesarean over the risk with spontaneous labor.
      CONCLUSION: Elective induction does not appear to increase the cesarean rate when
      the guidelines are met. Electively inducing labor with a low Bishop score
      increased the risk of cesarean, especially in nulliparas.

PMID- 17520396
TI  - Ultrasound screening for fetal major abnormalities at 11-14 weeks.
AB  - BACKGROUND: This study was planned to evaluate the efficiency of the 11-14 week
      scan in detecting fetuses with major fetal structural abnormalities. METHODS:
      Some 1,290 pregnant women were submitted to a routine ultrasound scan between the
      11th and 14th week after the detection of the fetal viability. The fetal anatomy
      was examined transabdominally, and in suspected cases transvaginally. Following
      the scans, the patients were examined in the second or third trimester of
      pregnancy. Fetal structural abnormalities classified as major and early onset
      were noted. Isolated choroid plexus cysts, cardiac defects not requiring
      treatment, mild ventriculomegaly, and mild renal pelviectasis in second trimester
      were not included. RESULTS: Twenty-four (1.86%) fetuses with various defects were
      identified, and 17 of these were diagnosed at the 11-14 week scan. The antenatal
      ultrasound detection rate of the fetuses with major anomalies was 95%, and 70%
      were detected in the first-trimester assessment. Four cardiac defects associated
      with genetic syndromes or requiring operation were included (0.31%) in this
      series. Two of the fetuses with cardiac defects (50%) had an increased nuchal
      translucency thickness. In this group, none of the fetuses with karyotype
      anomalies was born alive. CONCLUSIONS: The first-trimester scan is important in
      routine antenatal care for early detection of fetal defects, and determination of
      the fetuses at risk of cardiac anomalies and genetic syndromes.

PMID- 17520397
TI  - Self-administered measurement of symphysis-fundus heights.
AB  - BACKGROUND: Antenatal identification of infants small for gestational age (SGA)
      improves their perinatal outcome. Repeated measurement of symphysis-fundus (SF)
      heights performed by midwives is the most widespread screening method for
      detection of SGA. However, the inefficiency of this method necessitates improved
      practices. Earlier start and more frequent SF measurements, which could be
      accomplished by self-administered measurements, might improve the ability to
      detect deviant growth. The present study was set up to evaluate whether pregnant
      women can reliably perform SF measurements by themselves. METHOD: Forty healthy
      women with singleton and ultrasound-dated pregnancies from 2 antenatal clinics in
      Uppsala, Sweden, were asked to perform 4 consecutive SF measurements once every
      week, from 20 to 25 weeks of gestation until delivery. The self-administered SF
      measurements were recorded and systematically compared with midwives' SF
      measurements. RESULTS: Thirty-three pregnant women performed self-administered SF
      measurements over a 14-week period (range: 1-21). The SF curves constructed from
      self-administered SF measurements had the same shape as previously constructed
      population-based reference curves. The variance for self-administered SF
      measurements was higher than that of the midwives. CONCLUSIONS: Pregnant women
      are capable of measuring SF heights by themselves, but with higher individual
      variance than midwives. Repeated measurements at each occasion can compensate for
      the higher variance. The main advantage of self-administered SF measurements is
      the opportunity to follow fetal growth earlier and more frequently.

PMID- 17520398
TI  - Synergistic effect of renin-angiotensin system and nitric oxide synthase genes
      polymorphisms in pre-eclampsia.
AB  - BACKGROUND: Components of the renin-angiotensin system and endothelial nitric
      oxide synthase may co-operate in spiral artery remodelling during placentation,
      and thus reduce the uteroplacental resistance typical of normal pregnancy. Since
      lack of such remodelling and abnormal placentation are specific features of pre
      eclampsia, it has been suggested that abnormal function of both components of the
      renin-angiotensin system and endothelial nitric oxide synthase may be involved in
      its pathogenesis. However, previous studies of the association between pre
      eclampsia and polymorphisms of single genes encoding renin-angiotensin system
      components and endothelial nitric oxide synthase have yielded conflicting
      results. The aim of this study was to assess if interactions among different
      polymorphisms of the renin-angiotensin system and nitric oxide synthase are
      involved in the pathogenesis of pre-eclampsia. METHODS: Some 359 pregnant women
      were enrolled: 103 normotensive, 50 with chronic hypertension, 86 with
      gestational hypertension, and 120 with pre-eclampsia. DNA analysis was performed
      to evaluate angiotensin-converting enzyme I/D, angiotensin-II receptor 1 1166A/C,
      angiotensinogen M235T and endothelial constitutive nitric oxide synthase 4b/a
      polymorphisms. Odds ratios (OR) with 95% confidence interval (CI) and chi2 tests
      were calculated. RESULTS: The frequency of single gene polymorphisms was similar
      in each group. The frequency of pairs including the DD genotype of the
      angiotensin-converting enzyme I/D polymorphism plus other homozygous genotypes
      was significantly higher in pre-eclamptic patients than in controls (OR=3.04, 95%
      CI=1.16-7.93). CONCLUSIONS: Synergism of angiotensin-converting enzyme I/D and
      other polymorphisms of renin-angiotensin system components and nitric oxide
      synthase may be a risk factor for pre-eclampsia.

PMID- 17520399
TI  - Epidural ondansetron is more effective to prevent postoperative pruritus and
      nausea than intravenous ondansetron in elective cesarean delivery.
AB  - BACKGROUND: Postoperative pruritus, nausea, and vomiting are common side effects
      of intrathecal or epidural opioids. Intravenous ondansetron has been used for
      postoperative emesis. However, there are no reports regarding epidural
      ondansetron. Two studies were conducted to evaluate the prophylactic effects of
      epidural ondansetron for opioid-induced pruritus, nausea, and vomiting. METHODS:
      Neurotoxic signs were checked after epidural injection of ondansetron in rats. A
      clinical study was conducted to compare the prophylactic effects of epidural
      ondansetron with intravenous ondansetron for opioid-induced pruritus, nausea, and
      vomiting in cesarean delivery. RESULTS: No neurotoxic evidence was found in rats.
      The incidence of pruritus and nausea was significantly lower in the epidural
      ondansetron group than in the intravenous ondansetron group at 24 and 48 h
      postoperatively. CONCLUSIONS: Epidural ondansetron is more effective in
      preventing postoperative pruritus and nausea than intravenous ondansetron.

PMID- 17520400
TI  - Good accuracy of ultrasound estimations of fetal weight performed by midwives.
AB  - BACKGROUND: This study was undertaken to evaluate the quality of ultrasound
      estimation of fetal weight when performed by midwives experienced in ultrasound
      examinations. We also examined whether the accuracy was affected by fetal
      presentation, twin pregnancy or birth weight category. The results of 5 different
      formulas were compared to determine which was most accurate in our study
      population. METHODS: The study population consisted of 620 fetuses in 607
      pregnancies, on whom fetal weight estimations had been performed within 3 days
      prior to delivery. The group of twins (n=27) was analysed separately. Results
      achieved by Hadlock 2 formula used in our unit were compared with 4 other widely
      used formulas for estimation of fetal weight. RESULTS: With Hadlock 2 formula,
      mean absolute percent error was 6.2% and SD of error was 7.6% of mean birth
      weight. A total of 81% of estimates were within 10% of the actual birth weight.
      All the formulas tended to overestimate the weight of twins and fetuses weighing
      <2,500 g, and underestimate the weight of fetuses >4,000 g. Presentation of the
      fetus did not significantly influence the accuracy. The formula Hadlock 2, using
      3 parameters (biparietal diameter, abdominal circumference and femur length) gave
      the highest ICC of 0.910. CONCLUSIONS: Ultrasound estimation of fetal weight
      performed by midwives is feasible and of similar accuracy as in the original
      studies. Major errors may occur both in small and large birth weight groups.

PMID- 17520401
TI  - Infant mortality of very preterm infants by mode of delivery, institutional
      policies and maternal diagnosis.
AB  - OBJECTIVE: The aim of this study was to analyse infant mortality among infants
      born extremely preterm in relation to mode of delivery, maternal diagnosis, and
      different institutional policies. METHODS: We conducted a national tertiary
      health care center study using Swedish Medical Birth Register (MBR) data from
      1990 to 2002, to examine the 2,094 live births of infants at 23+0 to 27+6 weeks
      gestation. We assessed the association between mode of delivery, gestational age
      (GA), calendar year, maternal condition, and institutional policies on infant
      mortality outcome. RESULTS: At 23-25 weeks, 38% of infants (range: 34-69%) were
      delivered by cesarean section (CS), while at 26-27 weeks, 66% (59-80%) were
      delivered by CS. The CS rate for fetal or maternal indications was 98% in cases
      of pre-eclampsia/eclampsia, 42% for premature rupture of membranes (PROM), 68%
      for hemorrhage, 76% for PROM+hemorrhage, 56% for breech presentation, and 30% for
      preterm vertex with no other complications. After cases of pre
      eclampsia/eclampsia were excluded, vaginal delivery was associated with a small
      increase of risk for infant death. Vaginal delivery was associated with a
      significantly increased risk for infant death in breech presentations and
      multiple births, while vaginal delivery posed a non-significant risk increase for
      PROM and hemorrhage. For preterm vertex without any other complications, 4 out of
      5 infants were delivered vaginally without any risk increase. CONCLUSION: This
      study reports high CS rates for very preterm births at Swedish hospitals. In
      performing CS for very preterm infants, this study suggests a survival advantage
      for certain maternal conditions, but not for preterm labor with a vertex
      presentation without other obstetrical complications.

PMID- 17520402
TI  - Misoprostol-only versus mifepristone plus misoprostol in induction of labor
      following intrauterine fetal death.
AB  - BACKGROUND: Both misoprostol-alone and a combination of mifepristone plus
      misoprostol have been used in induction of labor in cases of intrauterine fetal
      death (IUFD). METHODS: Data from 130 women with IUFD at 21-42 weeks of gestation
      were analysed retrospectively. A total of 82 women received 100 microg (median)
      of misoprostol at 4-h intervals. Some 48 women received 200 mg of mifepristone,
      followed 19 h (median) later by single doses of 25 microg of misoprostol at 4-h
      intervals. RESULTS: The induction-to-delivery time did not differ between the
      groups (13.3 versus 12.8 h). However, between 21 and 25 weeks of gestation, the
      induction-to-delivery time was shorter with the combination regimen (p=0.04). The
      total dose of misoprostol needed was lower in the group pre-treated with
      mifepristone (p=0.0028). The 2 groups did not differ as regards complications
      experienced during labor and delivery. CONCLUSIONS: Both regimens, misoprostol
      only and the combination of mifepristone and misoprostol, are effective and safe
      in induction of labor after IUFD. Pre-treatment with mifepristone is more
      effective at earlier gestational weeks.

PMID- 17520404
TI  - Effects of maternal central hemodynamics on fetal heart rate patterns.
AB  - BACKGROUND: This study was undertaken to evaluate the effects of maternal central
      hemodynamics on fetal heart rate patterns near term, with special regard to the
      maternal body position. METHODS: Brief non-stress test and bioimpedance
      cardiography were carried out in the supine position, then repeated in a full
      left lateral decubitus position of mothers with singular, 36-39 week-old normal
      pregnancies in 106 cases. Computer-aided data were processed by SPSS statistic
      program. RESULTS: Due to the appearance of inferior vena cava syndrome,
      examinations had to be interrupted in 6 cases. Analysis of 100 complete
      registrations revealed a significantly increased number of accelerations, overall
      and short-term variations, and longer high episodes with lower basal fetal heart
      rates were found in the lateral decubitus than in the supine maternal position.
      Turning to the left resulted in a significant increase of the stroke volume;
      however, due to decreasing pulse rate, the cardiac output remained unchanged.
      Parameters of non-stress test showed correlations to hemodynamic indices. In the
      supine position, the short-term variation correlated with cardiac output
      (r=0.232, p=0.020); in the left lateral position, the number of accelerations
      correlated with stroke volume (r=0.221, p=0.027) and cardiac output (r=0.220,
      p=0.028). Changes of stroke volume due to altered body position correlated to
      similar changes of overall variation (r=0.264, p=0.018), and marginally to those
      of short-term variation (r=0.221, p=0.051). CONCLUSION: Maternal central
      hemodynamics influences fetal heart rate patterns in connection with different
      maternal body position.

PMID- 17520403
TI  - Regulation of amphiregulin, EGFR-like factor expression by hCG in cultured human
      granulosa cells.
AB  - BACKGROUND: It has long been suspected that the epidermal growth factor (EGF)
      receptor and some of its putative ligands may play an important role in ovarian
      function. Amphiregulin (AR) is the growth factor with an EGF-like motif, but its
      potential role in signalling in the ovary is still obscure. AR gene expression
      and its functional effect were evaluated in human granulosa cells from immature
      follicles. METHOD: Granulosa cells from immature follicles with early menstrual
      phase were cultured with or without 200 mIU/ml of FSH stimulation, following with
      or without 1 IU/ml of hCG. mRNA levels of AR and luteinising hormone replacement
      (LHR) were semi-quantified using RT-PCR. Progesterone (P) concentration in the
      medium was assayed. RESULTS: LHR mRNA was expressed 48 h after FSH stimulation
      without AR mRNA expression. AR mRNA was expressed 1 h after hCG stimulation, and
      increased the intensity in 6 h. P biosynthesis was increased by AR in a dose
      dependent manner. AR mRNA was elevated by forskolin stimulation without FSH and
      hCG stimulation before LHR mRNA expression. When cultured with FSH for 15 h,
      followed by increasing doses of hCG stimulation for 6 h, the AR mRNA levels
      increased according to hCG concentration up to 1,000 mIU/ml. CONCLUSION:
      Occurrence of LHR gene expression following FSH stimulation was necessary for the
      AR gene expression in vivo, and the AR gene was induced by forskolin without LHR
      gene expression in vitro. P biosynthesis was stimulated, to some extent, by AR.
      This result suggests the differentiation effect of AR on granulosa cells. AR
      might be a mediator of LH signals before ovulation.

PMID- 17520405
TI  - Testosterone versus clobetasol for maintenance of vulvar lichen sclerosus
      associated with variable degrees of squamous cell hyperplasia.
AB  - OBJECTIVE: To evaluate the therapeutic regimens and symptomatic response rates in
      patients with vulvar lichen sclerosus associated with variable degrees of
      squamous cell hyperplasia (mixed disease). MATERIAL AND METHODS: Eighty-three
      women with biopsy-proven vulvar mixed disease were evaluated for this
      retrospective study. All patients were initially treated with topical fluorinated
      corticosteroids, and then 2% testosterone propionate in petrolatum or 0.05%
      clobetasol 17-propionate (44 (53%) versus 39 (47%)). RESULTS: The remission rates
      were 82 and 93% in the testosterone and clobetasol subgroups at the end of 6
      months (p=0.112), respectively. The disease recurred in 8% of the patients. The
      recurrence rates in the testosterone and clobetasol arms were 13 and 5%,
      respectively (p=0.163). The histopathological review of the repeat vulvar
      biopsies of the patients without symptomatic relief revealed 6 (60%) patients
      with persistent disease, 2 (20%) with lichen sclerosus, 1 (10%) with atypical
      squamous hyperplasia, and 1 (10%) with VIN1. Two patients with recurrent disease
      and 2 patients with vulvar intraepithelial neoplasia I-II or atypical squamous
      hyperplasia were treated with skinning vulvectomy. CONCLUSIONS: Clobetasol
      resulted in higher remission and lower recurrence rates than those in
      testosterone therapy, although statistically significant differences were not
      obtained. In the evaluation of patients without symptomatic relief, the first
      step should be a vulvar biopsy to exclude the presence of atypical components.

PMID- 17520406
TI  - Attitudes to self-sampling of vaginal smear for human papilloma virus analysis
      among women not attending organized cytological screening.
AB  - BACKGROUND: The major problem with the cytological screening is the non-optimal
      participation rate among women invited for cervical smear collection. The aim of
      the present investigation was to examine the attitudes of the non-responding
      women to perform self-sampling of vaginal smear at home as a method to increase
      the coverage of the screening and to examine the prevalence of high-risk human
      papilloma virus (HPV) among the responding women. METHODS: From the database of
      the Department of Cytology, University Hospital of Uppsala 198 women, aged 35-55
      years, who had not attended the organized gynaecological screening for over 6
      years were identified. They were sent a letter of information about the study and
      one week later a self-sampling device aimed to collect vaginal smear. The vaginal
      smear of the women responding to the offer of self-sampling was analysed for high
      risk HPV using Hybrid Capture 2 method or polymerase chain reaction amplification
      of HPV DNA. All women in the study also received a questionnaire in order to
      investigate their attitudes towards self-sampling as an alternative in the
      organized screening. RESULTS: Of the 198 women 15 women had to be excluded. Fifty
      eight per cent of the women responded and collected vaginal smear at home and
      among them 7% were positive for high-risk HPV. The questionnaire revealed no
      significant difference of age, country of birth and occupation or marital status,
      on using self-sampling of vaginal smear at home. The attitudes among responding
      and non-responding women differed. The responding women who contributed by
      sampling vaginal smear were more positive to self-sampling of vaginal smear
      (p<0.01). CONCLUSIONS: Offering self-sampling of vaginal smear in women not
      attending the organized cytological screening increases the coverage and
      identifies an additional group of women with an increased risk to develop
      cervical cancer. The attitude towards self-sampling was mainly positive.

PMID- 17520407
TI  - VNTR I/I genotype of insulin gene is associated with the increase of follicle
      number independent from polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is accompanied by selective insulin
      resistance and enhanced ovarian steroidogenic effects of insulin. We analysed the
      minisatellite variations of the insulin gene (INS VNTR) with regard to the
      clinical features of PCOS. METHODS: Retrospective, adjusted association study.
      Infertile patients with PCOS (n=30) and tubal factor (n=75) were screened for
      anthropometrical, clinical and ovarian morphology parameters, as well as hormonal
      values. INS VNTR was genotyped by its surrogate marker at -23 HphI locus.
      RESULTS: INS VNTR genotype distribution was similar in PCOS and tubal infertility
      group. The mean ovarian follicle number was higher in VNTR I/I individuals
      compared to VNTR I/III and III/III individuals (adjusted OR=1.28, p=0.03),
      independent from the cause of infertility, the age, the follicle stimulating
      hormone level on day 3-5 of menstrual cycle, BMI and the previous surgical
      ovarian tissue removal. In addition, higher level of the luteinising hormone in
      VNTR I/I individuals was associated with the increase in follicle number.
      CONCLUSIONS: We suggest that INS VNTR genotypes are not associated with PCOS in
      general, but could have a certain influence on the phenotypic spectrum of the
      syndrome.

PMID- 17520408
TI  - Vaginal sacrospinous colpopexy and laparoscopic sacral colpopexy for vaginal
      vault prolapse.
AB  - BACKGROUND: Vaginal sacrospinous colpopexy (VSC) and laparoscopic sacral
      colpopexy (LSC) both correct vault prolapse. The present study compares the
      perioperative course and long-term results of VSC and LSC. METHODS: This
      retrospective study of post-hysterectomy vault prolapse involved 111 patients
      operated with either VSC (n=51) or LSC (n=60). The median time for the
      postoperative follow-up visit was 33.6 (range: 13-60) months for the LSC group
      and 38.4 (range: 7-108) months for the VSC group. Prolapse grade as well as the
      patient's satisfaction was recorded at the follow-up visit. RESULTS: Operation
      time was significantly shorter in the VSC group (median: 62 min) compared to the
      LSC group (median: 129 min). The rate of perioperative complications was low in
      both groups. There were 3 laparotomies in the LSC group, due to perioperative
      complications. The inpatients days were similar, with 3.7 days (1-18) and 4.0
      days (2-21) in the VSC and the LSC group, respectively. Surgery for the
      recurrence of vault prolapse at any time before the follow-up visit did not occur
      in the VSC group, but occurred in 7 patients in the LSC group. At the follow-up
      visit, there was no recurrence of vault prolapse in either group. The subjective
      success rate was 82% in the VSC and 78% in the LSC group. CONCLUSIONS: This study
      indicates that VSC and LSC are two equally effective surgical procedures to
      correct vaginal vault prolapse, but the LSC technique requires a longer operating
      time.

PMID- 17520409
TI  - Accuracy of preoperative tumor grade and intraoperative gross examination of
      myometrial invasion in patients with endometrial cancer.
AB  - BACKGROUND AND AIMS: Preoperative prediction of metastases to the regional lymph
      nodes in women with endometrioid endometrial cancer is a challenge. According to
      the Danish Gynaecological Cancer Society guidelines, a pelvic lymphadenectomy is
      warranted in all poorly differentiated tumors and all stage Ic disease. We have
      evaluated the accuracy of preoperative tumor grade and intraoperative gross
      examination of myometrial invasion, in predicting the need for a pelvic
      lymphadenectomy. METHODS: Preoperative tumor grade and intraoperative gross
      examination of myometrial invasion were prospectively registered in 72 women with
      stage I endometrioid endometrial cancer, operated between 1 September 2004 and 18
      April 2006. The pre- and intraoperative findings were compared with the final
      pathology report. RESULTS: The preoperative prediction of grade (well, moderate
      or poorly differentiated) was correct in 96% (69/72) of the patients. Gross
      examination of myometrial invasion correctly differentiated between stage Ia, Ib,
      and Ic disease in 89% (64/72) of the patients. The combination of preoperative
      tumor grade and intraoperative gross examination of myometrial invasion, led to
      wrong clinical decisions in 11% (8/72) of the patients. Three 'unnecessary'
      lymphadenectomies were performed, and 5 patients were primary operated upon
      without 'warranted' lymphadenectomy. CONCLUSIONS: Our data suggest that
      preoperative tumor grade and intraoperative gross examination of the uterus
      provide useful information for pre-and intraoperative planning of pelvic
      lymphadenectomy. However, wrong decisions were made in 11% of the patients, and
      more reliable evaluation methods are needed.

PMID- 17520410
TI  - The cervical cancer screening program from a midwife's perspective.
AB  - BACKGROUND: Midwives in Sweden are responsible for taking Papanicolaou (Pap)
      smears as part of the cervical cancer screening program. The aim of this study
      was to investigate midwives knowledge, experience and management of the cervical
      cancer screening program, and their apprehension of women's knowledge about Pap
      smear screening. METHODS: A postal questionnaire was sent to midwives working in
      primary health care in 3 different areas in Sweden. A total of 156 (77%) out of
      201 midwives completed the questionnaire. RESULTS: Four of 5 midwives considered
      themselves to have the education they needed to manage the screening program.
      However, the study indicated that midwives lacked a basic structure when giving
      information. As many as every third midwife refrained from or had an irrelevant
      answer to the proposed question, what is meant by a cellular atypia? Almost all
      midwives saw themselves as the main informant about Pap-smear screening. At the
      same time, the midwives perceived that women lacked knowledge about cellular
      atypia, and thought it was the same as cancer. Some 38% of the midwives expressed
      a wish to terminate the 'assembly line-like' screening system. The remaining
      midwives were completely satisfied with the organisation. CONCLUSIONS: Many
      midwives lacked time and a structured guidance when discussing screening and
      cervical atypia. Improvement in the organisation and certified education for Pap
      smear screening with access to recent research, could develop a more empowering
      exchange between the midwives and the women participating in cervical screening.

PMID- 17520411
TI  - Diagnosis and treatment of menorrhagia.
AB  - One-third of all women experience heavy menstrual bleeding at some point in their
      life. In western countries, about 5% of women of reproductive age will seek help
      for menorrhagia annually. Half of all women who consult for hypermenorrhea have
      some uterine abnormality, most often fibroids (among patients under 40 years of
      age) and endometrial polyps (above 40 years of age). Appropriate treatment
      considerably improves the quality of life of these patients, and it is important
      to make a rigorous assessment of the patient to provide the best treatment
      options. This guideline provides instructions on how to examine and treat women
      of fertile age who have menorrhagia. The subject's own assessment of the amount
      of menstrual blood loss does not generally reflect the true amount. All patients
      should undergo a pelvic examination and, if the menstrual pattern has changed
      substantially or if anaemia is present, a vaginal sonography should be carried
      out as the most important supplemental examination. Vaginal sonography combined
      with an endometrial biopsy is a reliable method for diagnosing endometrial
      hyperplasia or carcinoma, but it is insufficient for diagnosing endometrial
      polyps and fibroids; these can be diagnosed more reliably by sonohysterography or
      hysteroscopy. Non-steroidal anti-inflammatory drugs and tranexamic acid reduce
      menstrual blood loss by 20-60%, and the effectiveness of a hormonal intrauterine
      system (IUS) is comparable with that of endometrial ablation or hysterectomy.
      Cyclic progestogens do not significantly reduce menstrual bleeding of women who
      ovulate. Treatment should be started with one of the drug therapies, i.e. the
      IUS, tranexamic acid, anti-inflammatory drugs, or oral contraceptive. Drug
      treatment should be used and evaluated before surgical interventions are
      considered. With an effective training and feedback system, it is possible to
      organise the diagnostics, medical treatment and follow-up of heavy menstrual
      bleeding in the primary health care setting or in outpatient clinics, which
      reduces the burden on specialist health care.

PMID- 17520412
TI  - Cauda equina syndrome in early pregnancy: a case report.

PMID- 17520413
TI  - A case of placenta accreta complicated by severe IUGR and maternal coagulopathy.

PMID- 17520414
TI  - The rapid development of a giant condyloma acuminatum (Buschke-Lowenstein tumor)
      during pregnancy.

PMID- 17520415
TI  - Regarding Rogers MS, Yuen PM, Wong S. Avoiding manual removal of placenta:
      evaluation of intra-umbilical injection of uterotonics using the Pipingas
      technique for management of adherent placenta. Acta Obstet Gynecol. 2007;86:48
      54.

PMID- 17520419
TI  - Ablative therapy of liver tumors.

PMID- 17520420
TI  - Endovascular coiling of intracranial aneurysms using bioactive coils.

PMID- 17520421
TI  - Magnetic resonance imaging of the gallbladder: spectrum of abnormalities.
AB  - Various pathologies involving the gallbladder can manifest clinically, producing
      nonspecific clinical symptoms and making diagnosis difficult and challenging.
      Real-time sonography is the most widely used diagnostic study for the gallbladder
      and the primary screening examination of choice. With increasing use of magnetic
      resonance imaging (MRI) and MR cholangiopancreatography (MRCP), gallbladder
      pathology is frequently seen. Understanding the basic patterns of various disease
      manifestations and appearance on MRI is the key to making an accurate diagnosis.
      Given its inherent tissue contrast and contrast sensitivity, MRI in conjunction
      with MRCP can be a very valuable test in evaluating gallbladder pathology.
      Gallbladder pathology can be classified into congenital (such as absence),
      inflammatory (acute, hemorrhagic, and chronic cholecystitis), traumatic, benign
      (polyps) and malignant tumors (gallbladder carcinoma and lymphoma), and other
      disease processes can be seen in cholelithiasis, cholesterosis, thickened
      gallbladder wall, and Mirrizzi syndrome.

PMID- 17520422
TI  - Preoperative computed tomography-guided percutaneous hookwire localization of
      metallic marker clips in the breast with a radial approach: initial experience.
AB  - BACKGROUND: Hookwire localization is the current standard technique for
      radiological marking of nonpalpable breast lesions. Stereotactic directional
      vacuum-assisted breast biopsy (SVAB) is of sufficient sensitivity and specificity
      to replace surgical biopsy. Wire localization for metallic marker clips placed
      after SVAB is needed. PURPOSE: To describe a method for performing computed
      tomography (CT)-guided hookwire localization using a radial approach for metallic
      marker clips placed percutaneously after SVAB. MATERIAL AND METHODS: Nineteen
      women scheduled for SVAB with marker-clip placement, CT-guided wire localization
      of marker clips, and, eventually, surgical excision were prospectively entered
      into the study. CT-guided wire localization was performed with a radial approach,
      followed by placement of a localizing marker-clip surgical excision. Feasibility
      and reliability of the procedure and the incidence of complications were
      examined. RESULTS: CT-guided wire localization surgical excision was successfully
      performed in all 19 women without any complications. The mean total procedure
      time was 15 min. The median distance on CT image from marker clip to hookwire was
      2 mm (range 0-3 mm). CONCLUSION: CT-guided preoperative hookwire localization
      with a radial approach for marker clips after SVAB is technically feasible.

PMID- 17520423
TI  - Lymph drainage studied by lymphoscintigraphy in the arms after sentinel node
      biopsy compared with axillary lymph node dissection following conservative breast
      cancer surgery.
AB  - PURPOSE: To investigate lymphatic drainage as measured by lymphoscintigraphy in
      the arms of patients undergoing either sentinel lymph node biopsy (SNB) or
      axillary lymph node dissection (ALND). MATERIAL AND METHODS: From January 2001 to
      December 2002, 30 patients with unilateral invasive breast carcinoma underwent
      breast-conserving surgery with SNB and 30 patients with ALND. All patients
      received radiotherapy to the breast. Lymphoscintigraphy was performed, and skin
      circulation, skin temperature, and arm volume were measured 2-3 years after
      radiotherapy. RESULTS: None of the 30 patients who underwent SNB showed any
      clinical manifestation of lymphedema. Of the 30 patients undergoing ALND, six
      (20%) had clinical lymphedema, with an arm volume that was >10% larger on the
      operated than on the non-operated side (P<0.01). Scintigraphically, visual
      analysis revealed lymphatic dysfunction in three patients, manifested as forearm
      dermal back flow. Two of these patients also had an increased arm volume.
      Quantitative analysis showed no differences between the groups, apart from a
      smaller amount of isotope in the axilla in the ALND group. There was no
      difference in skin circulation or skin temperature. CONCLUSION: Our study shows
      that lymph drainage in the operated arm compared with the non-operated arm was
      less affected by SNB than by ALND, and that morbidity associated with SNB was
      lower than with ALND. However, the results do not confirm our hypothesis that
      lymphoscintigraphy can reveal differences in lymph circulation that are not
      evident clinically in the form of manifest lymphedema. The most sensitive
      clinical method of assessing lymph drainage seems to be measurement of arm
      volume.

PMID- 17520424
TI  - Occlusion of pulmonary arteriovenous malformations by use of vascular plug.
AB  - Pulmonary arteriovenous malformations are commonly treated by embolization with
      coils or balloons to prevent cerebral complications and to raise the oxygenation
      of the blood. The Amplatzer vascular plug is a new occlusive device made of a
      self-expanding cylindrical nitinol mesh. It is fast and safe to position, and can
      be repositioned before final delivery. It is especially suited for embolization
      of large high-flow vessels as in pulmonary arteriovenous malformations with big
      feeding arteries. Two cases of successful use of the new device for treatment of
      large pulmonary arteriovenous malformations are described.

PMID- 17520425
TI  - Magnetic resonance imaging in determination of myocardial ischemia and viability:
      comparison with positron emission tomography and single-photon emission computed
      tomography in a porcine model.
AB  - BACKGROUND: In patients with chronic left ventricular dysfunction, the size of
      the viable cardiac muscle is correlated with the prognosis and the outcome of
      myocardial revascularization. PURPOSE: To evaluate the diagnostic value of
      various imaging techniques in determination of myocardial ischemia and viability.
      MATERIAL AND METHODS: A chronic myocardial ischemia animal model was established,
      in which 10 pigs underwent magnetic resonance imaging (MRI), positron emission
      tomography (PET), and single-photon emission computed tomography (201Tl SPECT)
      before and 1-2 months after modeling. The size of myocardial ischemia and
      necrosis was judged, and the imaging manifestations were compared with pathologic
      findings. RESULTS: Seven of the 10 animals completed all examinations
      uneventfully. On dobutamine-stressed cine MRI, 10 (8.93%) segments were found to
      be akinetic. Perfusion was abnormal in 34 (30.35%) segments. Delayed
      hyperenhancement was observed in 12 (10.71%) segments. PET detected myocardial
      necrosis in 17 (15.18%) segments, and SPECT detected myocardial necrosis in nine
      (8.04%) segments. Histological examination with triphenyltetrazolium chloride
      (TTC) showed pale necrosis in 14 (12.50%) segments. The number of necrotic
      segments detected by PET was significantly greater than that by contrast-enhanced
      MRI (chi2 = 5, P = 0.0253, kappa = 0.8028) and cine MRI (chi2 = 7, P = 0.0082,
      kappa = 0.7079). It was also greater than that by TTC (chi2 = 3, P = 0.0833,
      kappa = 0.8879), although the difference was statistically insignificant. The
      number of necrotic segments detected by SPECT was significantly smaller than that
      by TTC (chi2 = 5, P = 0.0253, kappa = 0.7590), as was the number of necrotic
      segments detected by cine MRI (chi2 = 4, P = 0.0455, kappa = 0.8100). There was
      no statistically significant difference in the detection of necrotic segments
      between contrast-enhanced MRI and TTC (chi2 = 2, P = 0.1573, kappa = 0.9130).
      CONCLUSION: Cardiac MRI can determine viable myocardium and clearly delineate the
      location and degree of myocardial necrosis. PET slightly overestimates the extent
      of the necrotic myocardium and is unable to distinguish transmural necrosis from
      subendocardial necrosis.

PMID- 17520426
TI  - E-learning is a well-accepted tool in supplementary training among medical
      doctors: an experience of obligatory radiation protection training in healthcare.
AB  - PURPOSE: To evaluate the possibilities of Internet-based radiation protection
      training among referring physicians. MATERIAL AND METHODS: 324 referring
      physicians underwent an Internet-based radiation protection training course
      (www.prewise.com/radiationsafetytraining). Two hundred ten of them (96 female,
      114 male, aged 25-64 years) filled out the questionnaire, which included
      questions regarding their expectations for the course, its scope and schedule,
      and the benefit they derived from the course. In addition, we asked whether it
      was difficult to learn using the Internet, whether e-learning saved time, and
      whether they learned more or less effectively in comparison to conventional
      lectures. RESULTS: 75% found e-learning to be an easy way to study. Nineteen
      percent had previous experience in e-learning. Sixty-one percent found that it
      saved time, and 57% stated that they learned more effectively using e-learning in
      comparison to conventional lectures (22% chose "could not say"). Ninety-one
      percent found that the course fulfilled their expectations, and the scope and
      schedule were found convenient by 91% and 55% of subjects, respectively. Eighty
      four percent stated that they benefited from the course, and 94% were willing to
      study using the Internet in the future. No sex or age differences were found.
      Subjects working in the open ward (P = 0.028) and hospital (P = 0.004) found the
      course to be more timesaving than subjects working elsewhere. CONCLUSION: Finnish
      medical doctors are very positive about Internet-based learning. E-learning seems
      to be a well-accepted and practical learning method in healthcare.

PMID- 17520427
TI  - Factors predicting complete necrosis rate after ultrasound-guided percutaneous
      laser thermoablation of small hepatocellular carcinoma tumors in cirrhotic
      patients: a multivariate analysis.
AB  - PURPOSE: To assess factors affecting the effectiveness of percutaneous laser
      ablation (PLA) under ultrasound (US) guidance in terms of complete ablation
      achievement. MATERIAL AND METHODS: The clinical records of 86 hepatocellular
      carcinoma (HCC) tumors (mean diameter 23.7 mm) in 60 cirrhotic patients (mean age
      68.3 years; 36 males; 57 HCV+; 53 Child's class A, seven Child's class B) treated
      by means of PLA were reviewed. PLA was performed with a continuous-wave Nd:YAG
      laser by a single operator who positioned two to four 300-microm optic fibers
      advanced in 21-gauge needles into target lesions under US guidance. Triphasic
      computed tomography (CT) studies were used to verify treatment effectiveness 1
      month after PLA completion. The association between characteristics of the lesion
      and outcome (complete or incomplete ablation) was evaluated by logistic
      regression, taking into account the following predictive factors: tumor size,
      pattern of growth (infiltrating or not) at imaging, location, first diagnosis of
      HCC (naive tumors vs. non-naive tumors), number of sessions (1/ > 1), total
      delivered energy, and years of treatment in 2001-2002 (first period) vs. 2003
      2004 (second period). RESULTS: Complete ablation was obtained in 62 nodules
      (72%). Statistically significant predictors of incomplete ablation after the
      first PLA course at both univariate and multivariate analysis included:
      infiltrating growth pattern (odds ratio (OR) 12.3, P<0.002), non-naive tumors (OR
      8.7, P<0.001), and first period of treatment (OR 10.3, P<0.002). CONCLUSION: The
      effectiveness of US-guided PLA for HCC tumors < or =4 cm turned out to be
      negatively affected by both operator-related (the beginning of the operator's
      experience with the technique) and tumor-related factors (non-naive, infiltrating
      HCC tumors).

PMID- 17520428
TI  - Gadolinium contrast agent is of limited value for magnetic resonance imaging
      assessment of synovial hypertrophy in hemophiliacs.
AB  - PURPOSE: To examine the influence of different doses of gadolinium contrast agent
      on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of
      synovial hypertrophy and radiographic joint changes in hemophiliacs, and to
      investigate the value of gadolinium in MRI assessment of synovial hypertrophy in
      hemophiliacs using dynamic MRI and MRI scoring. MATERIAL AND METHODS: Twenty-one
      hemophiliacs on prophylactic factor treatment without recent bleeds were
      subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI
      of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the
      patients, the MRI procedure was repeated after a triple dose of gadoteridol.
      RESULTS: MRI findings of synovial hypertrophy were significantly correlated with
      Pettersson radiographic scores. In 19 of the 21 MRI investigated joints,
      administration of contrast agent did not alter the result of the evaluation of
      synovial hypertrophy. CONCLUSION: The optimal time interval for volume assessment
      of synovial hypertrophy after injection of gadolinium contrast agent is dose
      dependent. Hemophiliacs without recent bleeds have minor to abundant synovial
      hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not
      useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is
      not routinely indicated for MRI scoring of joints in hemophiliacs.

PMID- 17520429
TI  - Regionally specific compensation for bone loss in the tibial trabeculae of
      estrogen-deficient rats.
AB  - BACKGROUND: Bone mineral density (BMD) and microstructural variations have been
      extensively investigated in recent years; however, the compensation for bone loss
      between different regions is still unclear. PURPOSE: To fully characterize
      regional variations in bone mineral density (BMD) as well as the microstructure
      and dynamic changes of rat tibial trabeculae that occur with bone loss associated
      with estrogen deficiency. MATERIAL AND METHODS: Female Sprague-Dawley rats were
      ovariectomized (OVX), sham-operated (sham), or left unoperated (baseline
      control). The left tibiae were harvested at baseline, and at postoperative weeks
      3 and 15. High-resolution micro-computed tomography (microCT) was used to
      identify the densitometric and microstructural properties of trabeculae in the
      proximal ends of the rat tibia, specifically the epiphysis and metaphysis.
      RESULTS: Volumetric BMDs at the organ (organ BMD) and tissue (tissue BMD) levels
      were significantly higher for trabeculae at the epiphysis than metaphysis.
      Moreover, trabeculae at the epiphysis were thicker, and fewer in number and
      connectivity than those at the metaphysis, which were more rod like. Trabeculae
      at the metaphysis were more susceptible to bone loss induced by estrogen
      deprivation than at the epiphysis, and the regions varied greatly in their
      adaptation to this loss. At the metaphysis, trabecular tissue BMD and thickness
      were unexpectedly higher at postoperative week 15 than week 3 or baseline. In
      contrast, at the epiphysis, tissue BMD did not change with time, but trabecular
      thickness significantly increased at week 15 compared to baseline and was also
      greater in OVX compared to sham rats. CONCLUSION: Metaphyseal and epiphyseal
      trabeculae show regionally specific variations in BMD and microstructure. The
      former are more susceptible to bone loss induced by estrogen deficiency and would
      be strengthened by either hypertrophy or hypermineralization, while epiphyseal
      trabeculae are mainly strengthened by thickening.

PMID- 17520431
TI  - Intraoperative magnetic resonance imaging in neurosurgery.
AB  - Intraoperatively magnetic resonance (MR)-guided neurosurgical operations have
      been done since 1996, mostly for brain tumors. Several different concepts for
      intraoperative MRI procedures using low-, middle-, and high-field MR scanners
      have been reported from pioneering neurosurgical centers. In this article, we
      present the different solutions used in these centers from a practical point of
      view. More thoroughly, we present our own concept and experience of 160
      craniotomies since 1999 in an operation theater equipped with a low-field (0.23T)
      scanner, which can be turned on and off during surgery.

PMID- 17520432
TI  - Attempts to improve absolute quantification of cerebral blood flow in dynamic
      susceptibility contrast magnetic resonance imaging: a simplified T1-weighted
      steady-state cerebral blood volume approach.
AB  - BACKGROUND: Attempts to retrieve absolute values of cerebral blood flow (CBF) by
      dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) have
      typically resulted in overestimations. PURPOSE: To improve DSC-MRI CBF estimates
      by calibrating the DSC-MRI-based cerebral blood volume (CBV) with a corresponding
      T1-weighted (T1W) steady-state (ss) CBV estimate. MATERIAL AND METHODS: 17
      volunteers were investigated by DSC-MRI and 133Xe SPECT. Steady-state CBV
      calculation, assuming no water exchange, was accomplished using signal values
      from blood and tissue, before and after contrast agent, obtained by T1W spin-echo
      imaging. Using steady-state and DSC-MRI CBV estimates, a calibration factor K =
      CBV(ss)/CBV(DSC) was obtained for each individual. Average whole-brain CBF(DSC)
      was calculated, and the corrected MRI-based CBF estimate was given by CBF(ss) = K
      x CBF(DSC). RESULTS: Average whole-brain SPECT CBF was 40.1+/-6.9 ml/min x 100 g,
      while the corresponding uncorrected DSC-MRI-based value was 69.2+/-13.8 ml/min x
      100 g. After correction with the calibration factor, a CBF(ss) of 42.7+/-14.0
      ml/min x 100 g was obtained. The linear fit to CBF(ss)-versus-CBF(SPECT) data was
      close to proportionality (R = 0.52). CONCLUSION: Calibration by steady-state CBV
      reduced the population average CBF to a reasonable level, and a modest linear
      correlation with the reference 133Xe SPECT technique was observed. Possible
      explanations for the limited accuracy are, for example, large-vessel partial
      volume effects, low post-contrast signal enhancement in T1W images, and water
      exchange effects.

PMID- 17520433
TI  - Magnetic resonance imaging findings of adult-onset glutaric aciduria type I.
AB  - Glutaric aciduria or glutaric acidemia type I, an autosomal recessive disease,
      usually presents with an acute encephalopathic crisis in young children. We
      report the magnetic resonance (MR) and proton MR spectroscopy (MRS) imaging
      findings of a previously healthy 20-year-old man who presented with recurrent
      headaches. Organic acids from the patient's urine contained large amounts of
      adipate, glutarate, and 3-hydroxyglutarate consistent with glutaric aciduria type
      I.

PMID- 17520434
TI  - Magnetic resonance imaging findings in diffuse lymphangiomatosis:
      neuroradiological manifestations.
AB  - We report magnetic resonance (MR) findings in a patient with histologically
      proven lymphangiomatosis with a history of chylothorax, diffuse lung infiltrates,
      spinal involvement, cystic lesions of the mediastinum, and mesentery thickening.
      The patient also had diffuse infiltration of the right brachial plexus, with
      similar imaging findings as the spinal lesions. Although osseous and extraosseous
      involvement may be seen frequently with lymphangiomatosis, involvement of the
      brachial plexus has not been previously reported.

PMID- 17520435
TI  - Endovascular coiling of intracranial aneurysms using bioactive coils: a single
      center study.
AB  - BACKGROUND: Some degree of recanalization is reported in up to one-third of
      intracranial aneurysms treated with endovascular coiling. A technical development
      potentially effective in avoiding recanalization is the Matrix Detachable Coil
      (MDC), which is covered with a biodegradable polymeric material that enhances
      intra-aneurysmal clot organization and fibrosis. PURPOSE: To report the initial
      clinical experience of MDC for endovascular aneurysm coiling in a single-center,
      single-operator, and well-defined population setting. MATERIAL AND METHODS: 118
      aneurysms in 104 patients (73 with subarachnoid hemorrhage, SAH) were embolized
      with MDC alone (n = 52) or combined with bare platinum coils (n = 66). RESULTS:
      Initial aneurysm obliteration was class 1 (complete obliteration) in 45 aneurysms
      (38.1%), class 2 (residual neck) in 44 (37.3%), and class 3 (residual aneurysm)
      in 29 (24.6%). Procedure-related morbidity was 4.8%, and mortality 0.96%.
      Clinical follow-up of 61 patients with SAH (mean 5.9 months, range 1-17 months)
      showed good outcome (Glasgow Outcome Scale, GOS 4-5) in 39 (63.9%), and poor
      outcome or death (GOS 1-3) in 22 (36.1%). Imaging follow-up of 73 aneurysms
      (average 6.5 months, range 1-17 months) showed class 1 in 47 (64.4%), class 2 in
      18 (24.7%), and class 3 in eight (10.9%). Recanalization occurred in 11 aneurysms
      (15%), of which four (5.5%) required re-treatment. CONCLUSION: This study
      confirms that aneurysm coiling with MDC is feasible, effective, and safe.

PMID- 17520437
TI  - Neural mechanism of cognitive control impairment in patients with hepatic
      cirrhosis: a functional magnetic resonance imaging study.
AB  - BACKGROUND: Many studies have claimed the existence of attention alterations in
      cirrhotic patients without overt hepatic encephalopathy (HE). No functional
      magnetic resonance imaging (fMRI) study in this respect has been published.
      PURPOSE: To investigate the neural basis of cognitive control deficiency in
      cirrhotic patients using fMRI. MATERIAL AND METHODS: 14 patients with hepatic
      cirrhosis and 14 healthy volunteers were included in the study. A modified Stroop
      task with Chinese characters was used as the target stimulus, and block-design
      fMRI was used to acquire resource data, including four stimulus blocks and five
      control blocks, each presented alternatively. Image analysis was performed using
      statistical parametric mapping 99. After fMRI examinations were complete,
      behavior tests of Stroop interference were performed for all subjects. Overall
      reaction time and error numbers were recorded. RESULTS: Both healthy volunteers
      and patients with hepatic cirrhosis had Stroop interference effects. Patients
      with hepatic cirrhosis had more errors and longer reaction time in performing an
      incongruous color-naming task than healthy volunteers (P<0.001); there was no
      significant difference in performing an incongruous word-reading task (P =
      0.066). Compared with controls, patients with hepatic cirrhosis had greater
      activation of the bilateral prefrontal cortex and parietal cortex when performing
      the incongruous word-reading task. With increased conflict, activation of the
      anterior cingulate cortex (ACC), bilateral prefrontal cortex (PFC), parietal
      lobe, and temporal fusiform gyrus (TFG) was decreased when patients with hepatic
      cirrhosis performed the incongruous color-naming task. CONCLUSION: This study
      demonstrates that patients with hepatic cirrhostic have cognitive control
      deficiency. The abnormal brain network of the ACC-PFC-parietal lobe-TFG is the
      neural basis of cognitive control impairment in cirrhotic patients.

PMID- 17520438
TI  - Esophageal duplication cyst causing unilateral hyperinflation of the lung in a
      neonate.
AB  - Esophageal duplication cysts are rare congenital anomalies. Frequently
      asymptomatic, they may cause respiratory distress and feeding difficulties in
      infants. Unilateral hyperinflation of the lung due to compression of the bronchus
      by the cyst is rare. We report a case of a 4-day-old male neonate presenting with
      respiratory distress who had an esophageal duplication cyst causing obstructive
      hyperinflation of the right lung. The nature of the cyst was confirmed after
      surgery.

PMID- 17520439
TI  - A rare case of crossed renal ectopia with inflammatory abdominal aortic aneurysm.

PMID- 17520440
TI  - Stabilization and target delivery of Nattokinase using compression coating.
AB  - The aim of the work is to develop a new formulation in order to stabilize a
      nutraceutical enzyme Nattokinase (NKCP) in powders and to control its release
      rate when it passes through the gastrointestinal tract of human. NKCP powders
      were first compacted into a tablet, which was then coated with a mixture of an
      enteric material Eudragit L100-55 (EL100-55) and Hydroxypropylcellulose (HPC) by
      direct compression. The activity of the enzyme was determined using amidolytic
      assay and its release rates in artificial gastric juice and an intestinal fluid
      were quantified using bicinchoninic acid assay. Results have shown that the
      activity of NKCP was pressure independent and the coated tablets protected NKCP
      from being denatured in the gastric juice, and realized its controlled release to
      the intestine based on in vitro experiments.

PMID- 17520441
TI  - Pilot study of relative bioavailability of two oral formulations of ketoprofen 25
      mg in healthy subjects. A fast-dissolving lyophilized tablet as compared to
      immediate release tablet.
AB  - The pharmacokinetics of ketoprofen from a fast-dissolving lyophilized tablet
      (LT), which need not be swallowed, as compared to an immediate release (IR)
      tablet as reference after single oral dose (25 mg) administration was determined
      in six healthy subjects aged between 25-40 years using a randomized crossover
      design. In this study, the rate and extent of absorption of ketoprofen were found
      to be very different after administration of the LT and the IR tablet. The rate
      of absorption of ketoprofen from LT was significantly faster than that of IR
      tablet and had significantly higher Cmax (by about 50%) and earlier tmax (by 15
      min), whereas the extent of absorption expressed by AUC was about 68% higher as
      compared to the IR tablet. The relative bioavailability (frel) of the LT compared
      with the IR tablet was 168%. The difference between the two formulations for half
      life and MRT were statistically significant (p<0.05). The tolerance of the two
      tested formulations was excellent. Ketoprofen LT remained physically and
      chemically stable for 12 months at 25 degrees C and 60% relative humidity.

PMID- 17520442
TI  - Transdermal and buccal delivery of methylxanthines through human tissue in vitro.
AB  - We examined the in vitro permeation of central nervous stimulants - caffeine,
      theophylline, and theobromine across human skin with the aid of six chemical
      enhancers. It was found that oleic acid was the most potent enhancer for all
      three methylxanthines. Further optimization studies with different solvents
      showed that caffeine transport could be enhanced to give flux values up to 585
      microg/cm2.hr-1. Theobromine and theophylline delivery rates proved insufficient.
      An additional study involving a buccal tissue equivalent showed that this
      membrane was more permeable than skin for all model actives tested and would
      offer an alternate way of delivery.

PMID- 17520443
TI  - Fast-disintegrating sublingual epinephrine tablets: effect of tablet dimensions
      on tablet characteristics.
AB  - The purpose of this study was to evaluate the effect of changing dimensions on
      the hardness (H), disintegration time (DT), and wetting time (WT) of fast
      disintegrating epinephrine tablets for sublingual administration as potential
      first aid treatment for anaphylaxis. Tablet formulations I and II, containing 0%
      and 10% epinephrine bitartrate, respectively, and weighing 150 mg were prepared
      by direct compression. Formulations were compressed at a range of forces using an
      8/32'' die with concave punches (CP); a 10/32'' and an 11/32'' die with CP and
      flat punches (FP). Tablet weight variation, content uniformity, thickness, H, DT,
      and WT were measured. The 8/32'', 10/32'', and 11/32'' dies resulted in tablet
      thickness of ranges 0.25-0.19'', 0.17-0.1'', and 0.16-0.08'', respectively. The
      DT and WT using the 8/32'' die were<or=10 and<or=30 sec, respectively, at
      H<or=5.4+/-0.2 kg for formulation I, and H<or=5.4+/-0.3 kg for formulation II.
      The DT and WT were<or=10 and<or=30 sec, respectively, using 10/32'' die/CP,
      10/32'' die/FP, 11/32'' die/CP, and 11/32'' die/FP at H<or=6.2+/-0.6 kg,
      <or=6.8+/-0.4 kg, <or=4.9+/-0.1 kg, and<or=7.2+/-0.3 kg, respectively, for
      formulation I. For formulation II, the DT and WT were<or=10 sec and<or=30 sec,
      respectively, when H<4 kg. No difference in DT and WT was observed between
      concave and flat tablets. The 11/32'' and 10/32'' dies resulted in more ideal
      tablet dimensions for sublingual administration, but H must be maintained<4 kg to
      ensure rapid DT and WT.

PMID- 17520445
TI  - Interaction characteristics and thermodynamic behaviour of gatifloxacin by
      aluminium hydroxide.
AB  - The interaction pattern of gatifloxacin was temperature-dependent Langmuir
      isotherm, and the Langmuir coefficients increased as the temperature was raised.
      The perturbation experiment conducted on this system showed that the nature of
      interaction was irreversible. The enthalpy change is a positive value, indicating
      the existence of increased activation energy as the temperature is raised. The
      entropy value, 24.21 e.u. obtained in this system, indicated that the hydration
      shells of the ions were rather tightly bound. Intestinal permeation study also
      revealed the decreased bioavailability of gatifloxacin relatively to the presence
      of aluminium hydroxide. The strong adsorption of gatifloxacin by aluminium
      hydroxide is due to formation of complexes with cations of aluminium hydroxide
      through carboxyl and carbonyl groups of gatifloxacin.

PMID- 17520444
TI  - Short communication: in vivo evaluation of microemulsion system for oral and
      parenteral delivery of rutaecarpine to rats.
AB  - Rutaecarpine-loaded microemulsion composed of 10.8% polyethylene glycol 400, 7.2%
      Tween 80, 20% caster oil, and 62% water were previously reported to be physically
      and chemically stable for at least 6 months. For the development of a
      Rutaecarpine-loaded microemulsion, here we studied the pharmacokinetic profiles
      of rutaecarpine after oral and intravenous administration of rutaecarpine-loaded
      microemulsion compared to suspension. The AUC of rutaecarpine from microemulsion
      after oral and intravenous administration increased about three-fold compared
      with that from suspension. Furthermore, the rutaecarpine-loaded microemulsion
      gave significantly higher AUC and Cmax than did suspension, suggesting that the
      oral bioavailability of rutaecarpine in this microemulsion system could be
      enhanced due to the enhanced solubility of rutaecarpine by microemulsion. Thus,
      our results indicated that the microemulsion system composed of castor oil,
      polyethylene glycol 400, Tween 80, and water could be a more effective oral and
      parenteral dosage form for rutaecarpine.

PMID- 17520446
TI  - Influence of surfactant on the thermal behavior of marigold oil emulsions with
      liquid crystal phases.
AB  - Vegetable oils have been largely consumed owing to the interest of pharmaceutical
      and cosmetic industries in using natural raw materials. The production of stable
      emulsions with vegetable oils challenges formulators due to its variability in
      composition and fatty acids constitution within batches produced. In the present
      work, it was studied that the influence of the size of carbon chain and the
      number of ethylene oxide moieties of the surfactant on the thermal behavior of
      eight emulsions prepared with marigold oil stabilized by liquid crystal phases.
      Differential scanning calorimetry (DSC) was used to determine the thermal
      behavior of the emulsions. The ratio of bound water was calculated, being between
      29.0 and 42.0%, confirming the extension of the liquid-crystalline net in the
      external phase. Changing the lipophilic surfactant from Ceteth-2 to Steareth-2,
      there was an increase in the temperature of phase transition of the liquid
      crystal influencing the system stability. Calorimetric study is very useful in
      understanding the performance of liquid crystals with the increase of temperature
      and to estimate emulsions stability.

PMID- 17520447
TI  - A validated stability indicating LC method for Nateglinide.
AB  - A simple, isocratic, rapid and accurate reverse phase high-performance liquid
      chromatography (RP-HPLC) method was developed for the quantitative determination
      of Nateglinide. The developed method is also applicable for determination of
      related substance in bulk drugs. The chromatographic separation was achieved on a
      Hypersil C18 (250x4.6 mm 5 microm) column using aqueous mixture of 0.025 M
      potassium hydrogen phosphate and 0.1% triethyl amine, v/v (pH 3.0 with dilute
      phosphoric acid)-methanol (25:75, v/v) as a mobile phase. Solution concentrations
      were measured on a weight basis to avoid the use of an internal standard. The
      chromatographic resolutions between Nateglinide and its potential impurities A
      and B were found to be greater than four. Forced degradation studies were
      performed for Nateglinide using acid (0.5 N hydrochloric acid), base (0.5 N
      sodium hydroxide), oxidation (3% hydrogen peroxide) heat (60 degrees C) and UV
      light (254 nm). The limit of detection and limit of quantification of
      Nateglinide, impurities A and B were found to be 0.05 and 0.15 microg /mL,
      respectively for 20 microL injection volume. The percentage recovery of
      Nateglinide was ranged from 98.4 to 100.9. The percentage recovery of impurities
      in Nateglinide sample was ranged from 96.8 to 103.5. The developed RP-HPLC method
      was validated with respect to linearity, accuracy, precision, robustness, and
      forced degradation studies prove the stability indicating power of the method.

PMID- 17520448
TI  - In vitro studies on transdermal permeation of butorphanol.
AB  - The influence of the donor vehicles pH and the addition of laurocapram or
      transkarbam 12 as permeation enhancers on the transdermal permeation of
      butorphanol through human skin were examined with the aim of finding out about
      its possible use in the transdermal delivery system. As the pH of the donor
      vehicles rises, the mean value of butorphanol skin fluxes declines; an
      exponential relationship of the means of butorphanol flux values against the pH
      of the buffered aqueous donor vehicles has been demonstrated. The presence of 1%
      of transkarbam 12 (T12) or 5% of laurocapram (LC), respectively, in an
      isopropylmyristate (IPM) donor vehicle increased transdermal fluxes of
      butorphanol almost 2.5 times (58.1+/-5.7 microg cm-2 hr-1) or 1.5 times (36.4+/
      7.0 microg cm-2 hr-1), respectively, when compared to blank donors. Considering
      clinical and pharmacokinetic data on butorphanol, it is possible to expect that a
      transdermal preparation sized 20 cm2 and possessing flux values ranging between
      5.1 and 15.3 microg cm-2 hr-1 should be sufficient to achieve effective
      butorphanol transdermal fluxes, namely using IPM donors containing T12. In
      conclusion, butorphanol is a suitable candidate for transdermal administration
      and T12 is a very a suitable enhancer for it.

PMID- 17520449
TI  - Preparation of azithromycin nanosuspensions by high pressure homogenization and
      its physicochemical characteristics studies.
AB  - The azalide azithromycin was proved to be clinically effective against Gram
      positive and Gram-negative bacteria. But the low bioavailability caused by its
      poor solubility and gastrointestinal response limited its application in clinic.
      With the purpose of increasing its saturation solubility and dissolution
      velocity, azithromycin was produced as nanosuspensions by high pressure
      homogenization. Nanosuspensions could increase the drug-loading and reduce the
      administration dosage, thus the gastrointestinal response could be minimized. In
      order to enhance the stability of the nanosuspensions, we got the freeze-dried
      powder by lyophilization. After dispersed in distilled water, the nanoparticles
      had a bulk population of about 400 nm and a spherical figure (watched by
      transmission electron microscopy). The analysis of differential scanning
      calorimetry and powder X-ray diffraction demonstrated that the crystal state of
      azithromycin had changed. In vitro release studies showed that the dissolution
      rate of nanosuspension, compared with micronized powder, had been obviously
      increased.

PMID- 17520450
TI  - Scopolamine sublingual spray: an alternative route of delivery for the treatment
      of motion sickness.
AB  - The purpose of this study was to develop a sublingual drug delivery spray
      formulation of scopolamine hydrobromide (L-(-)-hyoscine hydrobromide) and to
      determine the absolute bioavailability of scopolamine hydrobromide following
      sublingual delivery and to investigate the effect of a bioadhesive on the
      pharmacokinetic parameters of this drug in a rabbit model. Rabbits received a
      single scopolamine free base equivalent sublingual dose of 100 microg/kg and this
      was compared to intravenous administration of the drug. Blood samples were
      collected at different time points, and plasma scopolamine concentrations were
      determined using a new sensitive and specific LC/MS analytical method which
      utilized electrospray ionization detection. The bioavailability of sublingual
      scopolamine was determined by comparing plasma concentrations after sublingual
      spray delivery with equivalent intravenous doses. Following delivery of the
      sublingual spray dose, the average Cmax was 1024.4+/-177 ng/mL, and the AUC value
      was found to be 61067.6+/-9605 ng.min/mL. Relative to the intravenous dose (100%
      bioavailability), the bioavailability was 79.8% after sublingual spray
      administration. The addition of 2% chitosan, a bio-adhesive material and an
      absorption enhancer, showed a significant improvement in scopolamine sublingual
      absorption (p<0.05) was observed. Considering the limitations of delivering
      scopolamine orally or transdermally to patients who experience motion sickness,
      the sublingual route of administration using a spray delivery dosage form, is a
      potential alternative modality for the prevention of nausea and vomiting
      associated with motion sickness.

PMID- 17520452
TI  - Eating disorders and substance abuse in Canadian men and women: a national study.
AB  - The objective of this study was to examine the co-morbidity between eating
      disorders and substance use in a large nationally representative sample of
      Canadian women and men while including varied measures of substance consumption
      and a wide range of substance classes. The research was based on secondary
      analyses of data collected, using multistage stratified probability sampling, by
      Statistics Canada in the Mental Health and Well-being cycle 1.2 of the Canadian
      Community Health Survey (CCHS). Data were collected mostly in face to face
      interviews using the Computer Assisted Personal Interviewing method. Data
      included the Eating Attitude Test (EAT-26), and modules of the short form of the
      Composite International Diagnostic Interview (CIDI-SF) to assess alcohol and drug
      use, dependence and interference. Alcohol interference and amphetamine use were
      associated with the risk for an eating disorder in both women and men. In the
      women sample only, risk for an eating disorder was associated with illicit drug
      use, dependence and interference, as well as with the number of substance classes
      used. The study findings support the importance of developing assessment
      instruments and treatment strategies that address the co-occurrence of eating
      disorders and substance use for both women and men.

PMID- 17520453
TI  - The Research Directions Survey: patient and parent perspectives of eating
      disorder research.
AB  - Seventy-two patients and parents completed the "Research Directions Survey"
      (RDS), consisting of an open-ended question and four rank-ordered lists. The RDS
      was designed to examine aspects of eating disorders (ED) that these individuals
      perceive as priorities for future research. The top three themes emerging from
      the open-ended question were treatment, family dynamics, and motivation for
      recovery. In the four ranking questions, respondents indicated low self-esteem,
      weight-related comments, body image distortions, and individual psychotherapy as
      most important for future research. This paper discusses the implications of our
      findings and directions for future research in ED.

PMID- 17520454
TI  - Eating disorders and body image concerns in Asian American women: assessment and
      treatment from a multicultural and feminist perspective.
AB  - Eating disorders are one of the most lethal psychiatric illnesses and affect
      millions of individuals worldwide. While they have been more typically attributed
      to middle class, Caucasian, adolescent females, current research suggests that
      there is a similar prevalence of eating disorders and their symptoms, especially
      body dissatisfaction, among Asian American girls and women. Despite this, very
      little research has investigated how culture and gender may impact the assessment
      and treatment of eating disorders for Asian American women. This review examines
      the literature on the prevalence of eating disorders and negative body image in
      Asian American women and describes current research on the efficacy of a variety
      of theoretical approaches for treatment, including psychodynamic, cognitive
      behavioral, and feminist perspectives. Recommendations for considering culture
      and gender when working clinically with Asian American women who experience
      eating concerns as well as suggestions for future research directions are
      provided.

PMID- 17520455
TI  - Comparisons between African American girls' and parents' perceptions of girls'
      weight concerns and weight control behaviors.
AB  - Weight concerns and weight control behaviors were evaluated among sixty 8-10 year
      old African American girls and their parents/caregivers. Girls completed the
      McKnight Risk Factor Survey and parents completed a modified version regarding
      perceptions of their daughters' concerns and behaviors. Significant correlations
      between girls' and parents' were seen for Overconcern with Weight and Shape (r =
      .56) and Weight Control Behaviors (r = .33). Parents' correctly identified 72% of
      girls' responses for Overconcern with Weight and Shape, 60% for Binge, 85% for
      Purging and 58% for Weight Control Behaviors scales using clinical cutoffs.
      However, more stringent agreement coefficients indicated generally poor
      concordance between girls and parents. The modified McKnight may be useful for
      assessing awareness of these issues.

PMID- 17520456
TI  - Disordered eating behavior and obsessive compulsive symptoms in college students:
      cognitive and affective similarities.
AB  - Few studies have examined the psychological similarities between disordered
      eating behavior and obsessive-compulsive (OC) symptoms. The present study
      examined relationships among disordered eating, OC symptoms, and three cognitive
      and affective variables (perfectionism, obsessive beliefs, and negative affect).
      The cognitive and affective variables were significantly associated with
      disordered eating and with OC symptoms in a sample of 160 college women. Results
      also indicated that perfectionism is an important link between disordered eating
      behavior and OC symptoms, although the nature of perfectionism differs somewhat
      for the two types of behavior. Implications of the current results and directions
      for future research are discussed.

PMID- 17520457
TI  - The relationship of family stability and family mealtime frequency with bulimia
      symptomatology.
AB  - The present study extended previous research reporting an association between
      frequency of family mealtimes and bulimia nervosa by exploring whether family
      mealtimes might be a component of a larger construct of family stability. One
      hundred thirty-four female undergraduates completed retrospective measures of
      family stability, frequency of shared family mealtimes, and a measure of bulimia
      symptomatology. Results indicate that family stability is a more comprehensive
      predictor of bulimia symptomatology than meal frequency alone. Implications for
      intervention and treatment options are discussed.

PMID- 17520458
TI  - Question and answer: neuroimaging in the treatment of eating disorders. What is
      neuroimaging and how can it be used to improve the treatment of eating disorders?

PMID- 17520460
TI  - Stories I tell my patients: where are you when you are eating?

PMID- 17520462
TI  - Vitamin levels in Behcet's disease.
AB  - OBJECTIVE: To determine the role of oxidative stress and the antioxidant defense
      mechanism in the etiopathogenesis of active and inactive Behcets disease. In line
      with this objective, the present study aimed to examine the levels of nitric
      oxide (NO) and malondialdehyde (MDA), which are the end products of oxidant
      stress, and vitamins, which are non-enzymatic antioxidants, for the diagnosis and
      particularly the follow-up of Behcet's disease. MATERIALS AND METHODS: The study
      group consisted of a total of 60 individuals: 40 of whom were Behcet's disease
      patients and 20 were healthy individuals. Of the 40 Behcet's patients, 29 had the
      active and 11 had the inactive (stable) form of the disease. RESULTS: Although
      plasma MDA and NO (its stable form nitrite) levels in the total patient group
      were statistically significantly higher than those in the control group (p<0.06),
      there was no statistically significant difference as such between inactive
      Behcet's patients and the control group (p>0.05). Vitamin E, C, B1, B2 and flavin
      mononucleotide (FMN) values were significantly lower in the patient group in
      comparison with the control group (p<0.05). There was no statistically
      significant difference in other vitamin values. DISCUSSION: It is contemplated
      that measurement of such oxidative stress factors as MDA and NO and an
      accompanying evaluation of the antioxidant defense system can be significant in
      the diagnosis and treatment follow-up of Behcet's disease.

PMID- 17520463
TI  - Etanercept and efalizumab treatment for high-need psoriasis. Effects and side
      effects in a prospective cohort study in outpatient clinical practice.
AB  - BACKGROUND: Since the beginning of 2005, etanercept and efalizumab are officially
      registered and reimbursed for the treatment of recalcitrant psoriasis in The
      Netherlands. OBJECTIVE: The evaluation of the efficacy, safety and adverse events
      of etanercept and efalizumab treatment in daily practice. METHODS: A prospective
      cohort study was carried out for patients treated with etanercept or efalizumab
      between February 2005 and March 2006. RESULTS: Over the past 13 months 45
      individuals were treated with etanercept and 17 subjects were treated with
      efalizumab. The cohort represented a high-need population. At week 12, 82% of the
      subjects treated with 2 x 50 mg etanercept/week and 71% of the subjects treated
      with 2 x 25 mg etanercept/week reached a PASI-50. Efficacy of etanercept
      treatment was comparable to the results of clinical trials. For efalizumab,
      efficacy in responding patients was also comparable to clinical trial data, but
      the percentage of dropouts was substantial. During biologic treatment, safety was
      preserved and mainly mild adverse events were reported. CONCLUSION: Etanercept
      and efalizumab are effective and safe treatments of psoriasis, even in a high
      need population. Etanercept was able to sustain the clinical improvement
      throughout 24 weeks, whereas efalizumab was not in 47% of subjects.

PMID- 17520464
TI  - Clobetasol propionate foam 0.05% as a novel topical formulation for plaque-type
      and scalp psoriasis.
AB  - OBJECTIVES: To establish the efficacy of clobetasol propionate foam 0.05% in
      patients with plaque-type psoriasis and scalp psoriasis. METHODS: We conducted an
      open-label study on 24 patients. Twelve patients affected by plaque-type
      psoriasis (group 1) and 12 patients with scalp psoriasis (group 2) applied
      clobetasol propionate foam 0.05% twice daily for 4 weeks. RESULTS: Clobetasol
      propionate foam 0.05% led to a reduction of the disease severity. After 2 weeks
      the PASI score decreased from 7.5 at baseline to 2.5 (range: 0.8-4.6, SD: 1.1) in
      group 1 and from 5.7 to 1.7 (range: 0.2-4.8, SD: 1.1) in group 2. At week 4, the
      mean PASI was 2 (range: 0.6-4, SD: 1) and 1.1 (range: 0.2-2.2, SD: 0.6) in groups
      1 and 2, respectively. In particular, at week 2, 83.3% of patients with plaque
      psoriasis and 75% with scalp psoriasis achieved an improvement of the PASI score
      from baseline> or =50% (PASI-50). At week 4, 91.6% of patients from group 1 and
      100% from group 2 achieved or maintained PASI-50, while 41.6% in group 1 and
      58.3% in group 2 demonstrated a further improvement, reaching PASI-75.
      CONCLUSION: The rapidity of effect and the good safety profile suggest a role for
      clobetasol propionate foam 0.05% in the management of both plaque-type and scalp
      psoriasis.

PMID- 17520465
TI  - Clinical efficacies of shampoos containing ciclopirox olamine (1.5%) and
      ketoconazole (2.0%) in the treatment of seborrhoeic dermatitis.
AB  - BACKGROUND: Ciclopirox olamine (CPO) is a broad-spectrum antifungal with anti
      inflammatory properties effective against the yeast implicated in seborrhoeic
      dermatitis, Malassezia spp. This study compared 1.5% CPO shampoo with 2.0%
      ketoconazole shampoo and placebo in scalp seborrhoeic dermatitis. METHODS: A
      randomized, double-blind, 4-week treatment period was preceded by a 2-week run-in
      period and followed by a 2-week run-out period. A total of 350 patients (150 CPO,
      150 ketoconazole, 50 placebo) were enrolled. Assessments included scalp area
      affected, the severity of scaling, erythema, itching and scaling, and overall
      signs and symptoms. RESULTS: Both shampoos were significantly more effective than
      placebo in reducing the area affected. The mean reduction from baseline to end of
      treatment was 48.2 cm(2) with CPO, 41.4 cm(2) with ketoconazole and 20.0 cm(2)
      with placebo. Patients rated the CPO shampoo as superior to placebo (p<0.001) and
      ketoconazole shampoo (p<0.05) on the basis of overall signs and symptoms.
      Assessments of itching and scaling were also significantly in favour of the CPO
      shampoo over placebo at the end of treatment. All three shampoos were well
      tolerated. CONCLUSIONS: CPO shampoo was superior to placebo and at least as
      effective as ketoconazole shampoo in treating scalp seborrhoeic dermatitis.
      Patients rated the overall improvement as better with CPO than with ketoconazole
      shampoo.

PMID- 17520466
TI  - Therapeutic options for cutaneous leishmaniasis.
AB  - BACKGROUND: Cutaneous leishmaniasis occurs worldwide in both old and new world
      countries with their own endemic foci. Many of those infected often experience a
      delay in diagnosis and inappropriate treatment. OBJECTIVES: To review the
      literature in terms of the various treatment options described for cutaneous
      leishmaniasis. METHODS: Literature on the treatment of cutaneous leishmaniasis
      retrieved by searching Index Medicus, PubMed and IndMed were reviewed. RESULTS
      AND CONCLUSION: Review reveals no uniform pattern or definite guidelines for its
      therapy. The varied and contradictory experience of different workers further
      confounds the clinicians involved in the care of these patients. Selection of an
      appropriate and customized treatment schedule is a discretion the treating
      clinician has to make.

PMID- 17520467
TI  - Prevention of chronic furunculosis with low-dose azithromycin.
AB  - BACKGROUND: Chronic furunculosis is a recurrent staphylococcal abscess of the
      hair follicle. Besides ensuring personal hygiene, the management consists of long
      term treatment with topical and systemic antibiotics. OBJECTIVE: An open-labeled,
      prospective study was conducted to assess the clinical and in vitro efficacy of
      azithromycin in the long-term suppressive treatment of chronic furunculosis.
      METHODS: Patients with a history of three or more episodes of furuncles were
      assigned to receive 12 weeks of suppressive treatment with azithromycin at a
      weekly dosage of 500 mg. In vitro susceptibility of azithromycin was evaluated
      with E-test. The primary efficacy parameter was complete absence of furuncles
      during the 3 months of azithromycin treatment. The secondary efficacy parameter
      was further absence of furuncles during the 3-month follow-up period. RESULTS: At
      the end of 3 months of therapy, azithromycin was found to be effective in 19
      (79.2%) of 24 patients; 18 of these patients remained in remission during the 3
      months of follow-up. All of the strains were methicillin-sensitive. The results
      of the E-test showed that 15 of 18 strains (83.3%) were susceptible to
      azithromycin. CONCLUSION: The results of this study indicate that azithromycin is
      an effective and safe alternative in the treatment of chronic furunculosis caused
      by methicillin-sensitive Staphylococcus aureus.

PMID- 17520468
TI  - Treatment of a tufted angioma with intense pulsed light.
AB  - Tufted angioma is a rare cutaneous angiomatous proliferation named because of its
      characteristic histologic pattern of grouped dermal capillary tufts. Lesions
      usually begin in infancy or early childhood but rarely are congenital. Clinical
      manifestations are dull red coalescent papules and plaques, most commonly located
      on the neck, shoulders, and upper back, and can sometimes be tender. Although
      transformation to malignancy has not been described, tufted angiomas do not tend
      to regress. Effective treatments reported in the literature are scarce. We report
      an adult case of tufted angioma, with unusual presentation as annular plaques,
      which was alleviated after treatment with intense pulsed light in terms of both
      cosmetics and discomfort.

PMID- 17520469
TI  - Successful colchicine administration in facial granulomas caused by cosmetic
      implants: report of a case.
AB  - Injectable cutaneous microimplants may occasionally cause either persistent local
      irritation or late skin reactions in the form of foreign body granulomas at the
      injected areas. Permanent elimination of the latter is not easily achieved. The
      skin of a female patient developed nodules along the treated sites on her face a
      few months following the last session of intracutaneous injections. Intralesional
      steroids offered temporary and incomplete clearance. Colchicine was administered
      orally for better results.

PMID- 17520470
TI  - Topical tacrolimus for the treatment of lichen simplex chronicus.
AB  - Owing to severe itching and scratching, the natural course of lichen simplex
      chronicus (LSC) is clinically characterized by typical lichenoid lesions. Topical
      corticosteroids are often used to treat LSC but after withdrawal a relapse will
      sometimes occur. Therefore, LSC can be difficult to treat over time. We report a
      13-year-old boy suffering from LSC on two symmetrical circumscribed areas on the
      temple, whose lesions healed completely with tacrolimus 0.1% ointment within
      approximately 9 months. During active treatment no adverse drug reaction was
      observed. The patient is completely free of symptoms 3 years after cessation of
      treatment. We conclude that topical tacrolimus can be used as an effective, long
      lasting therapeutic modality in treating LSC, especially in sensitive skin areas
      such as the face.

PMID- 17520471
TI  - Severe ichthyosis-related disorders in children: response to acitretin.
AB  - One case of keratitis ichthyosis deafness (KID) syndrome and two cases of bullous
      ichthyosiform erythroderma (BIE) were treated with systemic acitretin. The severe
      hyperkeratotic lesions improved dramatically with acitretin therapy in the KID
      case. Substantial improvement of the palmoplantar keratoderma was also observed.
      During follow-up, laboratory results remained within normal limits and no
      skeletal abnormalities were detected. The two cases with BIE also showed good
      responses to acitretin. Long-term follow-up of these cases showed that signs and
      symptoms were well under control and no adverse effects were noted.

PMID- 17520472
TI  - Acitretin treatment in acrokeratosis verruciformis of Hopf.
AB  - Acrokeratosis verruciformis of Hopf is a rare disorder and characterized by flesh
      coloured, wart-like, flat papules on the dorsum of the hands and feet. The
      disease is an autosomal disorder, but sporadic cases also occur. We present a 38
      year-old woman diagnosed with acrokeratosis verruciformis without family history
      and treated successfully with acitretin.

PMID- 17520474
TI  - How to address CPP and AMP translocation? Methods to detect and quantify peptide
      internalization in vitro and in vivo (Review).
AB  - Membrane translocation is a crucial issue when addressing the activity of both
      cell-penetrating and antimicrobial peptides. Translocation is responsible for the
      therapeutic potential of cell-penetrating peptides as drug carriers and can
      dictate the killing mechanisms, selectivity and efficiency of antimicrobial
      peptides. It is essential to evaluate if the internalization of cell-penetrating
      peptides is mediated by endocytosis and if it is able to internalize attached
      cargoes. The mode of action of an antimicrobial peptide cannot be fully
      understood if it is not known whether the peptide acts exclusively at the
      membrane level or also at the cytoplasm. Therefore, experimental methods to
      evaluate and quantify translocation processes are of first importance. In this
      work, over 20 methods described in the literature for the assessment of peptide
      translocation in vivo and in vitro, with and without attached macromolecular
      cargoes, are discussed and their applicability, advantages and disadvantages
      reviewed. In addition, a classification of these methods is proposed, based on
      common approaches to detect translocation.

PMID- 17520475
TI  - Quantification of the effects of a ryanodine receptor channel mutation on
      interaction with a ryanoid.
AB  - Understanding the nature of the interaction of the plant alkaloid ryanodine with
      its receptor channel (RyR) is important to aid interpretation of physiological
      studies and provide structure-function information about RyR. We present here the
      first quantitative description of the relative single-channel kinetic effects of
      a single-point mutation in RyR2. We exploit the well-characterized ryanoid 8beta
      amino-9alpha-hydroxyryanodine that displays reversible kinetics with RyR2. We
      explicitly show that the effect of the Q4863A mutation is to increase the
      apparent dissociation constant by increasing the apparent dissociation rate of
      the ryanoid. The voltage-dependence of the interaction displays no change. We
      infer that Q4863 is not involved with the voltage-drop but is able to influence
      ryanoid-bound structural changes. We discuss structural mechanisms by which this
      mutation could affect ryanoid interaction.

PMID- 17520476
TI  - Kv1 potassium channel C-terminus constant HRETE region: arginine substitution
      affects surface protein level and conductance level of subfamily members
      differentially.
AB  - We have shown previously that truncating all of the variable cytoplasmic C
      terminus of Kv1.1 potassium channels to G421stop had only a small inhibitory
      effect on their cell surface conductance density levels and cell surface protein
      levels. Here we investigated the role of a highly conserved cytoplasmic C
      terminal charged region of five amino acids (HRETE) of the S6 transmembrane
      domain in the protein and conductance expression of Kv1.1, Kv1.2, and Kv1.4
      channels. For Kv1.1 we found that E420stop, T419stop, and E418stop showed cell
      surface conductance densities and cell surface protein levels similar to full
      length control, whereas R417stop and H416stop exhibited essentially no
      conductance but their surface protein levels were similar to full length control.
      A bulky non-negatively charged hydrophilic amino acid at position 417 appeared to
      be critical for wild type gating of Kv1.1 because R417K and R417Q rescued
      conductance levels whereas R417A or R417E did not. The R417A mutation in the full
      length Kv1.1 also exhibited surface protein levels similar to control but it did
      not exhibit significant conductance. In contrast, mutation of the equivalent
      arginine to alanine in full length Kv1.2 and Kv1.4 appeared to have little or no
      effect on channel conductance but rather decreased cell surface protein levels by
      inducing partial high ER retention. These findings are consistent with the notion
      that the arginine amino acid in the HRETE region plays a different role in
      affecting conductance levels or cell surface protein levels of very closely
      related Kv1 potassium channels.

PMID- 17520478
TI  - Structural insight into an ankyrin-sensitive lipid-binding site of erythroid beta
      spectrin.
AB  - It was recently shown that the region within beta-spectrin responsible for
      interactions with ankyrin includes a lipid-binding site which displayed
      sensitivity to inhibition by ankyrin. We studied its structure by constructing a
      series of single and double spin-labeled beta-spectrin-derived peptides and
      analyzing their spin-spin distances via electron paramagnetic resonance
      spectroscopy and the Fourier deconvolution method. The results indicate that the
      whole ankyrin-sensitive lipid-binding site of beta-spectrin exhibits a helical
      conformation revealing a distinct 3(10)-helix contribution at its N-terminus. The
      start of the helix was located five residues upstream along the sequence compared
      to the theoretical predictions. A model based on the obtained data provides
      direct evidence that the examined lipid-binding site is a highly amphipathic
      helix, which is correlated with the specific conformation of its N-terminal
      fragment.

PMID- 17520477
TI  - Regulation of expression and kinetic modeling of substrate interactions of a
      uracil transporter in Aspergillus nidulans.
AB  - Early genetic evidence suggested that A. nidulans possesses at least one uracil
      transporter. A gene, named furD, was recently identified by reverse genetics and
      in silico approaches and we confirm here that it encodes a high-affinity, high
      capacity, uracil transporter. In this work, we study the regulation of expression
      of FurD and develop a kinetic model describing transporter-substrate
      interactions. The furD gene is not expressed in resting conidiospores, is
      transcriptionally activated and reaches a peak during the isotropic growth phase
      of conidiospore germination, and stays at a basic low level in mycelium.
      Transcriptional expression is correlated to uracil transport activity. Expression
      in a strain blocked in uracil biosynthesis (pyrG-) is moderately increased and
      extended to later stages of germination. The presence of excess uracil in the
      medium leads to down-regulation of furD expression and FurD activity. A detailed
      kinetic analysis using a number of pyrimidine and purine analogues showed that
      FurD is able to recognize with high-affinity uracil (Km 0.45 microM), thymine (Ki
      3.3 microM) and several 5-substituted analogues of uracil, and with moderate
      affinity uric acid and xanthine (Ki 94-99 microM). Kinetic evidence supports a
      model in which the positions N1-H, =O2, N3-H, =O4, as well as planarity play a
      central role for the substrate binding. This model, which rationalizes the unique
      specificity of FurD for uracil, is compared to and found to be very similar to
      analogous models for protozoan uracil transporters.

PMID- 17520479
TI  - Cationic lipids involved in gene transfer mobilize intracellular calcium.
AB  - Cationic lipids are efficient tools to introduce nucleic acids and proteins into
      cells. Elucidation of the mechanism and cellular pathways associated with such
      transport has been relatively tedious, even though significant progress has been
      made in the characterization of the intracellular trafficking of lipid/DNA
      complexes. Surprisingly little is known about the effects of these delivery
      vectors on cell functioning. In this report, we show that both cationic lipids
      and cationic lipid/DNA complexes mobilize the intracellular calcium. Removal of
      extracellular calcium did not significantly abolish this effect and preincubating
      cells with thapsigargin led to a decrease in [Ca2+]i, indicating that calcium was
      released mainly from internal calcium stores sensitive to thapsigargin.
      Pretreatment of the cells with the phospholipase C inhibitor U73122, blocked the
      [Ca2+]i rise, suggesting an inositol dependent mechanism.

PMID- 17520480
TI  - Sphingomyelin chain length influences the distribution of GPI-anchored proteins
      in rafts in supported lipid bilayers.
AB  - Glycosyl-phosphatidylinositol (GPI)-anchored proteins are enriched in cholesterol
      and sphingolipid-rich lipid rafts within the membrane. Rafts are known to have
      roles in cellular organization and function, but little is understood about the
      factors controlling the distribution of proteins in rafts. We have used atomic
      force microscopy to directly visualize proteins in supported lipid bilayers
      composed of equimolar sphingomyelin, dioleoyl-sn-glycero-3-phosphocholine and
      cholesterol. The transmembrane anchored angiotensin converting enzyme (TM-ACE)
      was excluded from the liquid ordered raft domains. Replacement of the
      transmembrane and cytoplasmic domains of TM-ACE with a GPI anchor (GPI-ACE)
      promoted the association of the protein with rafts in the bilayers formed with
      brain sphingomyelin (mainly C18:0). Association with the rafts did not occur if
      the shorter chain egg sphingomyelin (mainly C16:0) was used. The distribution of
      GPI-anchored proteins in supported lipid bilayers was investigated further using
      membrane dipeptidase (MDP) whose GPI anchor contains distearoyl
      phosphatidylinositol. MDP was also excluded from rafts when egg sphingomyelin was
      used but associated with raft domains formed using brain sphingomyelin. The
      effect of sphingomyelin chain length on the distribution of GPI-anchored proteins
      in rafts was verified using synthetic palmitoyl or stearoyl sphingomyelin. Both
      GPI-ACE and MDP only associated with the longer chain stearoyl sphingomyelin
      rafts. These data obtained using supported lipid bilayers provide the first
      direct evidence that the nature of the membrane-anchoring domain influences the
      association of a protein with lipid rafts and that acyl chain length hydrophobic
      mismatch influences the distribution of GPI-anchored proteins in rafts.

PMID- 17520481
TI  - Actin is not required for nanotubular protrusions of primary astrocytes grown on
      metal nano-lawn.
AB  - We used sub-micron metal rod decorated surfaces, 'nano-lawn' structures, as a
      substrate to study cell-to-cell and cell-to-surface interactions of primary
      murine astrocytes. These cells form thin membranous tubes with diameters of less
      than 100 nm and a length of several microns, which make contact to neighboring
      cells and the substrate during differentiation. While membrane protrusions grow
      on top of the nano-lawn pillars, nuclei sink to the bottom of the substrate. We
      observed gondola-like structures along those tubes, suggestive of their function
      as transport vehicles. Elements of the cytoskeleton such as actin fibers are
      commonly believed to be essential for triggering the onset and growth of tubular
      membrane protrusions. A rope-pulling mechanism along actin fibers has recently
      been proposed to account for the transport or exchange of cellular material
      between cells. We present evidence for a complementary mechanism that promotes
      growth and stabilization of the observed tubular protrusions of cell membranes.
      This mechanism does not require active involvement of actin fibers as the
      formation of membrane protrusions could not be prevented by suppressing
      polymerization of actin by latrunculin B. Also theoretically, actin fibers are
      not essential for the growing and stability of nanotubes since curvature-driven
      self-assembly of interacting anisotropic raft elements is sufficient for the
      spontaneous formation of thin nano-tubular membrane protrusions.

PMID- 17520482
TI  - Membrane topology of the endoplasmic reticulum to Golgi transport factor Erv29p.
AB  - Secretory proteins are transported from the endoplasmic reticulum to the Golgi
      apparatus via COPII-coated intermediates. Yeast Erv29p is a transmembrane protein
      cycling between these compartments. It is conserved across species, with one
      ortholog found in each genome studied, including the surf-4 protein in mammals.
      Yeast Erv29p acts as a receptor, loading a specific subset of soluble cargo,
      including glycosylated alpha factor pheromone precursor and carboxypeptidase Y,
      into vesicles. As the eukaryotic secretory pathway is highly conserved, mammalian
      surf-4 may perform a similar role in the transport of unknown substrates. Here we
      report the membrane topology of yeast Erv29p, which we solved by minimally
      invasive cysteine accessibility scanning using thiol-specific biotinylation and
      fluorescent labeling methods. Erv29p contains four transmembrane domains with
      both termini exposed to the cytosol. Two luminal loops may contain a recognition
      site for hydrophobic export signals on soluble cargo.

PMID- 17520483
TI  - Phosphatidylcholine is essential for efficient functioning of the mitochondrial
      glycerol-3-phosphate dehydrogenase Gut2 in Saccharomyces cerevisiae.
AB  - Gut2, the mitochondrial glycerol-3-phosphate dehydrogenase, was previously shown
      to become preferentially labelled with photoactivatable phosphatidylcholine (PC),
      pointing to a functional relation between these molecules. In the present study
      we analyzed whether Gut2 functioning depends on the PC content of yeast cells,
      using PC biosynthetic mutants in which the PC content was lowered. PC depletion
      was found to reduce growth on glycerol and to increase glycerol excretion, both
      indicating that PC is needed for optimal Gut2 functioning in vivo. Using several
      in vitro approaches the nature of the dependence of Gut2 functioning on cellular
      PC contents was investigated. The results of these experiments suggest that it is
      unlikely that the effects observed in vivo are due to changes in cellular Gut2
      content, in specific activity of Gut2 in isolated mitochondria, or in the
      membrane association of Gut2, upon lowering the PC level. The in vivo effects are
      more likely an indirect result of PC depletion-induced changes in the cellular
      context in which Gut2 functions, that are not manifested in the in vitro systems
      used.

PMID- 17520484
TI  - Energy-independent translocation of cell-penetrating peptides occurs without
      formation of pores. A biophysical study with pep-1.
AB  - Pep-1 is a cell-penetrating peptide (CPP) with the ability to translocate across
      biological membranes and introduce active proteins inside cells. The uptake
      mechanism used by this CPP is, as yet, unknown in detail. Previous results show
      that such a mechanism is endocytosis-independent and suggests that physical
      chemical interactions between the peptide and lipid bilayers govern the
      translocation mechanism. Formation of a transmembrane pore has been proposed but
      this issue has always remained controversial. In this work the secondary
      structure of pep-1 in the absence/presence of lipidic bilayers was determined by
      CD and ATR-FTIR spectroscopies and the occurrence of pore formation was evaluated
      through electrophysiological measurements with planar lipid membranes and by
      confocal microscopy using giant unilamellar vesicles. Despite pep-1 hydrophobic
      domain tendency for amphipathic alpha-helix conformation in the presence of
      lipidic bilayers, there was no evidence for membrane pores in the presence of pep
      1. Furthermore, alterations in membrane permeability only occurred for high
      peptide/lipid ratios, which induced the complete membrane disintegration. Such
      observations indicate that electrostatic interactions are of first importance in
      the pep-1-membrane interactions and show that pores are not formed. A peptide
      lipid structure is probably formed during peptide partition, which favours
      peptide translocation.

PMID- 17520485
TI  - Differential regulation of mouse equilibrative nucleoside transporter 1 (mENT1)
      splice variants by protein kinase CK2.
AB  - Nucleosides are accumulated by cells via a family of equilibrative transport
      proteins (ENTs). An alternative splice variant of the most common subtype of
      mouse ENT (ENT1) has been identified which is missing a protein kinase CK2
      (casein kinase 2) consensus site (Ser(254)) in the central intracellular loop of
      the protein. We hypothesized that this variant (mENT1a) would be less susceptible
      to modulation by CK2-mediated phosphorylation compared to the variant containing
      the serine at position 254 (mENT1b). Each splice variant was transfected into
      nucleoside transporter deficient PK15 cells, and stable transfectants assessed
      for their ability to bind the ENT1-selective probe [(3)H]nitrobenzylthioinosine
      (NBMPR) and to mediate the cellular uptake of [(3)H]2-chloroadenosine, with or
      without treatment with the CK2 selective inhibitor, 4,5,6,7
      tetrabromobenzotriazole (TBB). mENT1a had a higher affinity for NBMPR relative to
      mENT1b - measured both directly by the binding of [(3)H]NBMPR, and indirectly via
      inhibition of [(3)H]2-chloroadenosine influx by NBMPR. Furthermore, incubation of
      mENT1b-expressing cells with 10 microM TBB for 48 h decreased both the K(D) and
      B(max) of [(3)H]NBMPR binding, as well as the V(max) of 2-chloroadenosine uptake,
      whereas similar treatment of mENT1a-expressing cells with TBB had no effect. PK15
      cells transfected with hENT1, which has Ser(254), was similar to mENT1b in its
      response to TBB. In conclusion, inhibition of CK2 activity, or deletion of
      Ser(254) from mENT1, enhances transporter affinity for the inhibitor, NBMPR, and
      reduces the number of ENT1 proteins functioning at the level of the plasma
      membrane.

PMID- 17520486
TI  - Using hydropathy features for function prediction of membrane proteins.
AB  - A novel alignment-free method for computing functional similarity of membrane
      proteins based on features of hydropathy distribution is presented. The features
      of hydropathy distribution are used to represent protein families as hydropathy
      profiles. The profiles statistically summarize the hydropathy distribution of
      member proteins. The summation is made by using hydropathy features that
      numerically represent structurally/functionally significant portions of protein
      sequences. The hydropathy profiles are numerical vectors that are points in a
      high dimensional 'hydropathy' space. Their similarities are identified by
      projection of the space onto principal axes. Here, the approach is applied to the
      secondary transporters. The analysis using the presented approach is validated by
      the standard classification of the secondary transporters. The presented analysis
      allows for prediction of function attributes for proteins of uncharacterized
      families of secondary transporters. The results obtained using the presented
      analysis may help to characterize unknown function attributes of secondary
      transporters. They also show that analysis of hydropathy distribution can be used
      for function prediction of membrane proteins.

PMID- 17520487
TI  - Syntaxin and VAMP association with lipid rafts depends on cholesterol depletion
      in capacitating sperm cells.
AB  - Sperm cells represent a special exocytotic system since mature sperm cells
      contain only one large secretory vesicle, the acrosome, which fuses with the
      overlying plasma membrane during the fertilization process. Acrosomal exocytosis
      is believed to be regulated by activation of SNARE proteins. In this paper, we
      identified specific members of the SNARE protein family, i.e., the t-SNAREs
      syntaxin1 and 2, and the v-SNARE VAMP, present in boar sperm cells. Both
      syntaxins were predominantly found in the plasma membrane whereas v-SNAREs are
      mainly located in the outer acrosomal membrane of these cells. Under non
      capacitating conditions both syntaxins and VAMP are scattered in well-defined
      punctate structures over the entire sperm head. Bicarbonate-induced in vitro
      activation in the presence of BSA causes a relocalization of these SNAREs to a
      more homogeneous distribution restricted to the apical ridge area of the sperm
      head, exactly matching the site of sperm zona binding and subsequent induced
      acrosomal exocytosis. This redistribution of syntaxin and VAMP depends on
      cholesterol depletion and closely resembles the previously reported
      redistribution of lipid raft marker proteins. Detergent-resistant membrane
      isolation and subsequent analysis shows that a significant proportion of syntaxin
      emerges in the detergent-resistant membrane (raft) fraction under such
      conditions, which is not the case under those conditions where cholesterol
      depletion is blocked. The v-SNARE VAMP displays a similar cholesterol depletion
      dependent lateral and raft redistribution. Taken together, our results indicate
      that redistribution of syntaxin and VAMP during capacitation depends on
      association of these SNAREs with lipid rafts and that such a SNARE-raft
      association may be essential for spatial control of exocytosis and/or regulation
      of SNARE functioning.

PMID- 17520489
TI  - A computer-controlled contracture correction device with low-load and continuous
      torque: an animal experiment and prototype design for clinical use.
AB  - The purpose of this study was to clarify the relationship between mechanical
      stress and tissue response of the contracted knee joint in rats and to propose a
      new design of contracture correction device for clinical use. Wistar rats were
      operated on to immobilize their knee joints with a procedure causing
      periarticular bleeding and were kept in flexed position for 40 days. At day 40,
      the immobilizing wire was removed, and after day 43, the contracted knee joint
      had been treated with tunable corrective devices secured by an external fixation
      method to the rear limb. These devices consisted of four types of motor-driving
      system which provided several different low-load and continuous stretch torques.
      Measuring the angle of maximum knee extension, its effectiveness was assessed
      comparing with a lower load and control group of natural recovery course. The
      device also had a cyclic joint movement within the acquired range of motion and
      an oval cam mechanism producing a small distraction force to the joint along its
      long axis. The results showed that an appropriate range of low-load continuous
      torque was more effective to correct joint contracture. On the basis of the
      animal experiment, a new computer-controlled, gas-driven contracture correction
      device was developed for clinical trial. It was concluded that mechanical
      application in a condition with low and continuous torque is a useful treatment
      for fixed joint contracture.

PMID- 17520490
TI  - Carbon fibre reinforced plastic knee-ankle-foot orthosis with a partially
      flexible thigh cuff: a modification for comfort while sitting on a toilet seat.
AB  - At the request of a polio survivor, a partially flexible thigh cuff made of
      leather and canvas for a carbon KAFO was devised to allow the wearer to feel more
      comfortable while sitting on a toilet seat. The original, acrylic resin, thigh
      cuff was partially excised to make an opening (15x10 cm), which was stuffed with
      rubber sponge, and was sealed with leather and canvas. The opening's surround was
      vertically and horizontally reinforced with carbon fibres. This modification
      provided relief to the polio survivor from the discomfort previously experienced
      while sitting on a toilet seat, and satisfied her needs in daily life.

PMID- 17520491
TI  - A prospective study on the development of critical thinking skills for student
      prosthetists and orthotists in Hong Kong.
AB  - Critical thinking skill is considered to be one of the important attributes to
      nurture students to cope with the challenges coming from this ever-changing
      world. The training of critical thinking skill could be quite different from the
      conventional education. Thus, special arrangements should be considered in the
      curriculum design and effective assessment method should be employed to test the
      subsequent learning outcome. This study was to evaluate prospectively the
      development of critical thinking disposition of the student prosthetists and
      orthotists in Hong Kong and a validated instrument, the California Critical
      Thinking Disposition Inventory (CCTDI) was used. The results showed that there
      was significant improvement in 5 out of the 7 domains, namely Truthseeking, Open
      mindedness, Systematicity, Analyticity, Critical thinking self-confidence,
      Inquisitiveness and Maturity of judgment in 3 years' time. Further curriculum
      enhancements were suggested as the sum of all the domains was just slightly above
      the threshold of positive tendency.

PMID- 17520492
TI  - Living with thalidomide: health status and quality of life at 40 years.
AB  - Thalidomide was first synthesized in 1953 and was subsequently marketed as a mild
      hypnotic and sedative in more than 20 countries. By 2001 it was estimated that
      there were 5,000 survivors from the 10,000 - 12,000 babies who were, as a result,
      born with severe abnormalities. For these survivors, recent concerns have emerged
      about their physical state, in particular their levels of pain and their ability
      to maintain independence. It was therefore wished to ascertain health status and
      current concerns amongst a sample of survivors living in the UK. A combination of
      qualitative and quantitative methodologies was employed. Qualitative interviews
      were undertaken with a sample drawn from the population affected by thalidomide
      known to the Thalidomide Trust. Selection of participants was based upon a
      theoretical sample frame. Postal questionnaires to examine health status and
      various psychosocial aspects concerned with living with the consequences of
      thalidomide were sent subsequently to these same participants and to a random
      sample of those not originally drawn for the qualitative interviews. For the
      qualitative interviews, 28 agreed to take part; two refused and the remainder did
      not respond. Those agreeing to interview were representative of the original
      compensation bands (Chi-Square = 3.929; p = 0.416). Several themes emerged from
      these interviews, including the effects on work and career; coping in terms of
      attitude to life, self-image, confidence, self-esteem, stress and emotion;
      relationships, independent living issues and emergent problems such as pain,
      quality of life, and anxiety about the future. A postal questionnaire was then
      sent to those who had agreed to interview (28), plus a random sample of the
      remaining group who were not initially chosen for the qualitative interviews. In
      total 82 people were sent the questionnaire, of whom 41 (50%) responded. Two
      thirds of responders were female. Seven out of ten lived with a partner, and over
      half (56%) had children. Almost half (46%) were in work, but 32% reported they
      were permanently unable to work because of disability. Current levels of
      impairment were found to be similar across groups defined by the original
      compensation band. In contrast, the activity limitation measures showed a steep
      gradient across bands but only 37% considered themselves disabled. Nevertheless,
      despite the restriction in activities for some, levels of participation were
      similar across bands; likewise simple summary items on health status and quality
      of life were similar and 70% reported their quality of life (QoL) was good or
      better than good. Yet nine in ten believed that their body was less flexible than
      in the past. Almost as many reported they were less able to carry things. It
      turns out that when compensation bands were grouped (1 - 3, 4 - 5) to highlight
      those most severely affected according to the original assessment, then those in
      the higher band grouping reported significantly more musculoskeletal problems,
      high levels of fatigue and increasing dependency and feelings of vulnerability.
      It is clear that the original ranking of disability severity, as expressed
      through the compensation, bands (allocated in early childhood in most cases), is
      consistent with current ranking of limitations in activity and participation.
      Nevertheless, despite high levels of disability amongst some survivors, lifelong
      adjustments to the original impairments have resulted in more than two thirds
      reporting at least a good quality of life. However, survivors expressed
      increasing concern about emerging musculoskeletal and other problems which may
      compromise hard-won independence.

PMID- 17520493
TI  - Validation of a patient activity monitor to quantify ambulatory activity in an
      amputee population.
AB  - The ability to objectively measure an amputee's walking activity over prolonged
      periods can provide clinicians with a useful means of evaluating their patients'
      outcomes. The present study aimed to validate the temporospatial data output from
      a commercially available ambulatory activity monitor (PAM, Ossur) fitted to trans
      tibial and trans-femoral amputees, against data that was simultaneously captured
      from a three dimensional motion analysis system (Qualisys Medical AB, Gothenburg,
      Sweden). Results indicate that the PAM monitor provides accurate measures of
      temporospatial aspects of amputee gait for walking speeds above 0.75 m/s.

PMID- 17520494
TI  - Measuring quality of life in prosthetic practice: benefits and challenges.
AB  - There is an increasing awareness that the inclusion of quality of life as an
      outcome measure is important in ensuring a client-centred and holistic
      assessment. This review outlines the benefits of quality of life as an outcome
      measurement in the field of prosthetics. It introduces the key concepts and
      challenges in the definition and assessment of quality of life post-amputation,
      including the relative advantages and disadvantages of adopting generic,
      disease/condition specific, dimension specific and individualized measures of
      quality of life. In conclusion, the review delineates and recommends issues and
      guidelines for consideration when undertaking quality of life research and
      assessment. A co-ordinated approach by practitioners in the field of prosthetics
      is necessary to ensure the inclusion of quality of life as an outcome measure and
      to ensure its measurement in a standardized and rigorous manner.

PMID- 17520495
TI  - Mechanical testing of prosthetic feet utilized in low-income countries according
      to ISO-10328 standard.
AB  - This report summarizes the results from 1132 ISO-10328 standard tests performed
      on 21 different prosthetic foot models commonly utilized in the developing world.
      None of the tested feet passed the strictest ISO testing protocol. All but one
      failed at the initial Static Proof test, which simulates a single momentary
      overload, due to permanent forefoot deformation. In addition, all tested feet had
      significant internal failures that were visible when sectioned longitudinally.
      Static Proof testing revealed average permanent deformation of the forefoot of
      all feet that exceeded the optional 5 mm ISO requirement. Forefoot deformation
      for non-Jaipur rubber feet came closest to meeting the standard at 8.3+/-3.4 mm;
      deformation of the various types of rubber Jaipur feet was the greatest at 22.5+/
      5.4 mm. Forefoot deformation for polyurethane (PU) feet was 13.6+/-5.5 mm.
      Forefoot deformation of the ethyl-vinyl-acetate (EVA) feet was slightly greater
      than the Jaipur feet at 22.8+/-5.7 mm. After the Static Strength test, which
      simulates a higher momentary overload, permanent deformation of the feet
      increased. The average maximum deformation for rubber SACH forefeet varied from
      17 - 30 mm, and 11 - 26 mm for the heel; Jaipur forefeet 47 - 60 mm and heels 13 
      19 mm; PU forefeet 20 - 44 mm and heels 20 - 33 mm; and EVA forefeet 33 - 50 mm
      and heels 16 - 31 mm. After completion of the Cyclic Test the prosthetic feet
      were sawn in half and closely examined visually. All feet revealed internal
      derangements: (i) Deformation of rubber or PU foam under the keel of forefoot
      and/or heel: HCMC, VI, EB1, BAVI, HI Cambodia, Myanmar, Angola, TATCOT, Kingsley
      and CR; (ii) Delamination from the keel: Mozambique, PHN, and Pro-cirugia; and
      (iii) Delamination between foam layers: BMVSS, NISHA, MUKTI, and OM. The
      influence of the two environmental factors tested was minimal for rubber feet
      with respect to deformation and inconsistent for the polymer feet; in particular
      for the forefeet. Creep increased with humidity exposure in some feet of natural
      rubber. However, creep decreased with ultraviolet (UV) exposure for these natural
      rubber feet, as was also the case for EVA feet, whereas the creep increased for
      two PU feet. Comparison of the effect of humidity and UV exposure generally
      showed less creep with UV exposure. In conclusion, ISO-10328 testing prior to
      release of a new foot construction for amputee use appears to be useful in the
      developing countries as well as in the developed world, even though it does not
      simulate the wear on the plantar surface that is seen clinically in barefoot
      walking. Inspection of the internal structures after the laboratory testing has
      been shown to reveal occult failure mechanisms in all tested feet.

PMID- 17520496
TI  - Comment on Salawu et al.

PMID- 17520498
TI  - Comment on Geake et al.

PMID- 17520502
TI  - Fossils, molecules, divergence times, and the origin of lissamphibians.
AB  - A review of the paleontological literature shows that the early dates of
      appearance of Lissamphibia recently inferred from molecular data do not favor an
      origin of extant amphibians from temnospondyls, contrary to recent claims. A
      supertree is assembled using new Mesquite modules that allow extinct taxa to be
      incorporated into a time-calibrated phylogeny with a user-defined geological time
      scale. The supertree incorporates 223 extinct species of lissamphibians and has a
      highly significant stratigraphic fit. Some divergences can even be dated with
      sufficient precision to serve as calibration points in molecular divergence date
      analyses. Fourteen combinations of minimal branch length settings and 10 random
      resolutions for each polytomy give much more recent minimal origination times of
      lissamphibian taxa than recent studies based on a phylogenetic analyses of
      molecular sequences. Attempts to replicate recent molecular date estimates show
      that these estimates depend strongly on the choice of calibration points, on the
      dating method, and on the chosen model of evolution; for instance, the estimate
      for the date of the origin of Lissamphibia can lie between 351 and 266 Mya. This
      range of values is generally compatible with our time-calibrated supertree and
      indicates that there is no unbridgeable gap between dates obtained using the
      fossil record and those using molecular evidence, contrary to previous
      suggestions.

PMID- 17520503
TI  - Detecting and overcoming systematic errors in genome-scale phylogenies.
AB  - Genome-scale data sets result in an enhanced resolution of the phylogenetic
      inference by reducing stochastic errors. However, there is also an increase of
      systematic errors due to model violations, which can lead to erroneous
      phylogenies. Here, we explore the impact of systematic errors on the resolution
      of the eukaryotic phylogeny using a data set of 143 nuclear-encoded proteins from
      37 species. The initial observation was that, despite the impressive amount of
      data, some branches had no significant statistical support. To demonstrate that
      this lack of resolution is due to a mutual annihilation of phylogenetic and
      nonphylogenetic signals, we created a series of data sets with slightly different
      taxon sampling. As expected, these data sets yielded strongly supported but
      mutually exclusive trees, thus confirming the presence of conflicting
      phylogenetic and nonphylogenetic signals in the original data set. To decide on
      the correct tree, we applied several methods expected to reduce the impact of
      some kinds of systematic error. Briefly, we show that (i) removing fast-evolving
      positions, (ii) recoding amino acids into functional categories, and (iii) using
      a site-heterogeneous mixture model (CAT) are three effective means of increasing
      the ratio of phylogenetic to nonphylogenetic signal. Finally, our results allow
      us to formulate guidelines for detecting and overcoming phylogenetic artefacts in
      genome-scale phylogenetic analyses.

PMID- 17520504
TI  - Estimating species phylogeny from gene-tree probabilities despite incomplete
      lineage sorting: an example from Melanoplus grasshoppers.
AB  - Estimating phylogenetic relationships among closely related species can be
      extremely difficult when there is incongruence among gene trees and between the
      gene trees and the species tree. Here we show that incorporating a model of the
      stochastic loss of gene lineages by genetic drift into the phylogenetic
      estimation procedure can provide a robust estimate of species relationships,
      despite widespread incomplete sorting of ancestral polymorphism. This approach is
      applied to a group of montane Melanoplus grasshoppers for which genealogical
      discordance among loci and incomplete lineage sorting obscures any obvious
      phylogenetic relationships among species. Unlike traditional treatments where
      gene trees estimated using standard phylogenetic methods are implicitly equated
      with the species tree, with the coalescent-based approach the species tree is
      modeled probabilistically from the estimated gene trees. The estimated species
      phylogeny (the ESP) is calculated for the grasshoppers from multiple gene trees
      reconstructed for nuclear loci and a mitochondrial gene. This empirical
      application is coupled with a simulation study to explore the performance of the
      coalescent-based approach. Specifically, we test the accuracy of the ESP given
      the data based on analyses of simulated data matching the multilocus data
      collected in Melanoplus (i.e., data were simulated for each locus with the same
      number of base pairs and locus-specific mutational models). The results of the
      study show that ESPs can be computed using the coalescent-based approach long
      before reciprocal monophyly has been achieved, and that these statistical
      estimates are accurate. This contrasts with analyses of the empirical data
      collected in Melanoplus and simulated data based on concatenation of multiple
      loci, for which the incomplete lineage sorting of recently diverged species posed
      significant problems. The strengths and potential challenges associated with
      incorporating an explicit model of gene-lineage coalescence into the phylogenetic
      procedure to obtain an ESP, as illustrated by application to Melanoplus, versus
      concatenation and consensus approaches are discussed. This study represents a
      fundamental shift in how species relationships are estimated - the relationship
      between the gene trees and the species phylogeny is modeled probabilistically
      rather than equating gene trees with a species tree.

PMID- 17520505
TI  - [Cholinesterase inhibitors and Alzheimer's disease: meta-analysis of the
      verification of effectiveness, origin and bias of results in published studies].
AB  - BACKGROUND AND OBJECTIVE: The cholinesterase-inhibitors (AChE-I) donepezil,
      galantamine and rivastigmine are currently used in the symptomatic treatment of
      patients with Alzheimer's dementia (AD) and the associated cholinergic deficits
      as well as those with other forms of dementia. Three aspects were analysed: (1)
      data on their clinical efficacy, (2) differences between North-American and
      international studies, and (3) potential publication biases. METHODS: Included
      were data from randomized, placebo-controlled, double-blind parallel group trials
      on more than 100 patients who had been treated for > or =12 weeks for AD, VaD,
      dementia with Lewy bodies, dementia with Parkinson's disease or with mild
      cognitive impairment. RESULTS: These large published trials support the clinical
      efficacy of AChE-I in patients with mild to moderate AD and other forms of
      dementia with regard to cognition and global impression. there was a trend
      towards greater beneficial cognitive effects in North-American studies, but this
      was non-significant. There was no evidence of a publication bias. CONCLUSIONS:
      Published data provide evidence for the clinical efficacy of donepezil,
      galantamine and rivastigmine in patients with mild to moderate AD. There is no
      indication that these results are critically influenced by the origin or a bias
      of the publication.

PMID- 17520507
TI  - [Establishment of renal cell carcinoma metastasis in the inferior vena cava and
      in the right atrium].

PMID- 17520506
TI  - [Cholangitis with hepatic microabscesses caused by Salmonella enterica serovar
      choleraesuis].
AB  - HISTORY AND ADMISSION FINDINGS: A 71-year-old man was admitted to the emergency
      unit of another hospital with a mild gastroenteritis and high fever. On admission
      g-GT and C-reactive protein (CRP) levels were markedly elevated. Under
      nonspecific antibiotic therapy with ampicillin/sulbactam the fever persisted and
      for the first time, on day 5, the patient complained of right-sided abdominal
      pain. An increase in the laboratory values indicated cholestasis. After changing
      the antibiotics to ceftriaxon and metronidazole, acute cholangitis being
      suspected, the fever subsided immediately and the CRP level decreased. The
      patient was discharged after seven days of antibiotic treatment. But he was once
      more admitted after four weeks to another hospital because of severely reduced
      general condition and mild fever. He was transferred to our unit after two weeks.
      INVESTIGATIONS AND DIAGNOSIS: The test values indicated cholestasis and CRP was
      markedly elevated, while aminotransferase activity was slightly increased and
      normocytic normochromic anemia developed. Viral hepatitis, autoimmune and
      metabolic liver diseases, toxic liver damage, extrahepatic cholestasis and an
      endocarditis were excluded. Bile was aspirated by endoscopic retrograde
      cholangiopancreatography and added to blood culture bottles. Salmonella enterica
      serovar choleraesuis var. Kunzendorf was isolated. TREATMENT AND FURTHER COURSE:
      The patient was treated with ciprofloxacin, 2 x 250 mg by mouth for a total of
      five weeks. After 17 days of treatment no Salmonella bacteria were grown from a
      newly aspirated bile sample and the patient became free of fever. CONCLUSION:
      Salmonella infections do not always present as gastroenteritis. Bacteremia should
      be considered in the differential diagnosis of such infections. If cholangitis
      persists, the aspiration of bile for microbiological tests can be a rational
      diagnostic step and facilitates treatment. Prolonged administration of
      antibiotics is necessary to avoid relapse. and follow-up is very important when
      treatment is finished.

PMID- 17520508
TI  - [Multimodal therapy of small cell and non-small cell lung carcinoma].
AB  - Lung cancer is divided into two types: non-small cell and small cell lung cancer.
      Small-cell lung cancer is a very aggressive rapid growing tumour type treated
      primarily with chemotherapy and, in the minority of patients with limited
      disease, with radiotherapy. Non-small cell lung cancer is treated in a
      multidisciplinary way with surgery, radiotherapy and chemotherapy depending on
      stage. Surgery is the mainstay of treatment for early stage non-small cell lung
      cancer patients. Adjuvant therapy has become state of the art in stage II and
      IIIA patients and must be considered in stage IB. Stage III patients should be
      treated in a multimodal way with radiotherapy and chemotherapy, and, if possible,
      with surgery. Treatment for every stage III patient should be discussed in a
      multidisciplinary team. Stage IV patients in good performance status will benefit
      from a combination chemotherapy, preferably platinum-based. Second line therapy
      has become standard and targeted therapies are under evaluation and are common in
      second line chemotherapy.

PMID- 17520509
TI  - [Contrast enhanced ultrasound of the liver--state of the art].
AB  - The diagnostic process, differential diagnosis and continuing routine follow-up
      of patients with focal liver lesions require an easily available, reliable and
      cost-effective diagnostic method. Ultrasound is a widely used method for the
      detection of liver lesions, but it has generally been regarded as inferior to
      contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI).
      Recent advances in contrast-enhanced ultrasound (CEUS) have improved the
      detection rate to a level similar to that attained with CT and MRI. Because of
      the high spatial resolution of ultrasound, CEUS can also detect metastases
      smaller than 1 cm. This has been demonstrated in several single-centre studies
      and recently also a European multi-centre study. This review focuses on the
      recent advances of CEUS in detecting and characterizing focal liver lesions.

PMID- 17520510
TI  - [William Harvey, discoverer of the blood circulation].
AB  - William Harvey (1578-1657), living at the turn to modern times, scientifically
      speaking, was an eminent physician and scientist. He developed the concept of the
      circulation of the blood and his findings have proved to be correct in nearly all
      details to this day. He published his physiological findings and interpretations
      in a small, albeit epoch-making, volume: Exercitatio anatomica de motu cordis et
      sanguinis in animalibus, published in Frankfurt in 1628. On the occasion of the
      350th anniversary of his death on June 3, 2007, this essay commemorates the work
      of this important physician, illustrating his brilliant conception of the blood
      circulation by quoting passages from De motu cordis et sanguinis.

PMID- 17520511
TI  - [Release from doctor-patient confidentiality with respect to private health
      insurance companies].

PMID- 17520513
TI  - The immunological milieu of the liver.
AB  - From the immunology standpoint, the liver is a peculiar organ for several reasons
      that range from its anatomical location to its cytoarchitecture and its variety
      of specific functions. Receiving blood directly from the digestive system, the
      liver is the crossroad at which the majority of antigens enter the organism.
      Hence, the milieu of the liver must provide a finely tuned balance between
      generating tolerance to self as well as to nonpathogenic molecules and
      microorganisms and producing an appropriate immune response to pathogens.
      Knowledge of the mechanisms that effectively maintain this balance is critical to
      the understanding of the pathogenesis of chronic inflammatory liver diseases,
      infectious, autoimmune, and others. Several theories have been proposed to
      explain what causes one or another response to take precedence. Although no
      definitive answer is yet available, the critical elements include, for tolerance,
      the particular cytoarchitectural features and the intrahepatic existence of
      antigen-presenting cells and, for immunity, inflammatory expressions including
      type 1 cytokines and chemokines, notably CCR5. Herein we review the available
      data on immune responses in the liver with particular emphasis on the unique
      structural and functional features of this "lymphoid" organ.

PMID- 17520514
TI  - The impact of autoimmunity on hepatocytes.
AB  - In this article, the impact of autoimmunity on the hepatocyte is analyzed in
      three distinct settings: classical autoimmune hepatitis, chronic hepatitis C
      virus infection with autoimmune manifestations, and de novo autoimmune hepatitis
      after liver transplantation. (1) Classical autoimmune hepatitis: Using as model
      autoimmune hepatitis type 2, whose main autoantigen is known, complementary
      aspects of the autoimmune response are revisited, including the targeting of
      discrete antigenic regions by humoral and cellular effectors of damage and a
      defect in the counterbalancing immunoregulatory mechanisms. (2) Chronic hepatitis
      C virus infection: This condition provides clues to the possible role of viruses
      as triggers of autoimmunity. The interaction between hepatitis C virus and its
      receptor on B lymphocytes is the likely trigger of a polyclonal activation
      leading to the production of autoantibodies. These appear not to be an
      epiphenomenon but to be markers of hepatocyte damage. (3) De novo autoimmune
      hepatitis after liver transplantation: The intriguing observation that autoimmune
      hepatitis can arise de novo after liver transplantation is presented and its
      possible pathogenic mechanisms are discussed.

PMID- 17520515
TI  - Chronic infections with hepatotropic viruses: mechanisms of impairment of
      cellular immune responses.
AB  - Chronic hepatitis B and C cause significant morbidity and mortality worldwide.
      Antiviral therapy suppresses but does not eliminate chronic hepatitis B virus
      (HBV) infection, and it is effective in only half of all hepatitis C virus (HCV)
      infected patients. Because adaptive immune responses are associated with
      spontaneous resolution of acute HBV and HCV infection, therapeutic enhancement of
      immune responses has been proposed as alternative or supplementary therapy for
      chronic infection. However, all efforts have been hampered by poor proliferation
      and effector functions of HBV- and HCV-specific CD4 and CD8 T cells, which are
      thought to be due to T cell exhaustion, high antigenic load, and viral escape.
      Recent studies revealed that endogenous factors, such as regulatory T cells,
      immunosuppressive cytokines, and inhibitory receptors, also contribute to the
      impairment of virus-specific T cell responses in chronic infection, perhaps
      reflecting the host's attempt to protect itself against immune-mediated
      pathology. These endogenous mechanisms and potential avenues to revert them are
      the subject of this review.

PMID- 17520516
TI  - Interpreting serological tests in diagnosing autoimmune liver diseases.
AB  - Autoimmune liver diseases (ALD) are characterized by immune-mediated injury of
      bile ducts or hepatocytes, thus including cholangiopathies such as primary
      biliary cirrhosis (PBC), primary sclerosing cholangitis, and autoimmune
      hepatitis. Further, ALD variants manifesting with both hepatocellular and
      cholangiocellular damage are becoming more common. Serum autoantibodies, together
      with imaging and histology, are critical to the diagnostic process when ALD is
      suspected. Because an early diagnosis can influence prognosis, the development of
      sensitive and specific tests for serum autoantibodies should be a priority for
      researchers to ensure a more efficient noninvasive workup. Little prognostic
      value has been observed for any of the ALD serum hallmarks, and a vigorous effort
      to investigate new and old markers should therefore be undertaken in longitudinal
      studies as in the recent paradigm of PBC-specific antinuclear antibodies. We
      review herein the numerous ALD screening tests available in routine and
      specialized laboratories and comment on their significance in clinical practice.

PMID- 17520517
TI  - The role of cytokines and chemokines in the development of steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) share
      similar morphological characteristics despite the obvious etiological differences
      between the two conditions. In both conditions the first manifestation of injury
      is the accumulation of fat within hepatocytes (steatosis), and in a proportion of
      patients this is followed by the development of necroinflammatory activity that
      leads to cirrhosis. Steatosis alone is considered to be relatively innocuous and
      is usually reversible, and it is the development of liver cell ballooning and
      inflammation (steatohepatitis) that determines whether a patient progresses to
      irreversible liver damage and fibrosis. This has led to the two-hit theory in
      which the first hit is accumulation of fat in the liver and the second hit
      involves an inflammatory insult or challenge to the liver, for example, through
      oxidative stress or in response to pathogenic stimuli such as endotoxin. Although
      the nature of the hits remains poorly understood, it is clear that the critical
      event in progression is the development of inflammation, and the fact that it is
      impossible to distinguish alcoholic from nonalcoholic steatohepatitis on
      histological grounds suggests that common pathogenic mechanisms are involved. We
      focus on the role of cytokines and particularly chemokines in instigating and
      driving the inflammatory infiltrate in steatohepatitis. A better understanding of
      this process might allow therapeutic intervention to switch off the inflammatory
      response before irreversible damage occurs in both ALD and NAFLD.

PMID- 17520518
TI  - The liver: a special case in transplantation tolerance.
AB  - Liver transplants are not often rejected in patients weaned from
      immunosuppression and are spontaneously accepted in some animal models. We review
      past and recent findings of liver transplantation and propose a unified model in
      which several mechanisms act in concert to induce and maintain tolerance in both
      naive and effector T cell compartments. First, passenger leukocytes migrate to
      lymphoid tissues and induce apoptosis of alloreactive naive T cells. Second,
      antigen-specific activation and subsequent deletion of naive and effector cells
      within the liver itself purge the repertoire of alloreactive T cells. Other
      mechanisms such as microchimerism and migration of donor dendritic cells to the
      thymus may play a predominant role in maintaining tolerance, and soluble major
      histocompatibility complex molecules, donor peptides, and regulatory T cells may
      participate in the induction and maintenance phases. Thus, the major challenge in
      liver transplantation will be to favor these tolerogenic processes while
      developing strategies that specifically inhibit alloreactive memory T cells.

PMID- 17520519
TI  - Guidelines for therapy of autoimmune liver disease.
AB  - The principle of therapy for chronic inflammatory liver diseases is the removal
      of causal agents. For autoimmune liver diseases, however, total removal of causal
      agents and immune cells is impossible. Therefore, autoimmune liver diseases are
      presently treated by suppression of the immune response. Autoimmune hepatitis is
      characteristically responsive to corticosteroids, often used in combination with
      azathioprine to obtain a steroid-sparing effect. For primary biliary cirrhosis,
      ursodeoxycholic acid is safe and is the first choice for treatment. Treatment of
      this autoimmune liver disease should also address various symptoms and
      complications arising from any associated autoimmune diseases, particularly
      cholestasis and cirrhosis-related complications. For primary sclerosing
      cholangitis there are no established immunomodulatory therapies, but medical,
      endoscopic, and surgical treatments are applicable to this disease. Liver
      transplantation becomes indicated during the eventual end stages of each of these
      immune-mediated liver diseases.

PMID- 17520520
TI  - Fibrin ring granuloma in chronic hepatitis C: virus-related vasculitis and/or
      immune complex disease?
AB  - Fibrin ring granulomas are rare lesions whose pathophysiology has remained
      somewhat elusive. It has been suggested that these peculiar lesions are related
      to focal vasculitis with endothelial injury and deposition of immune complexes.
      Fibrin ring granulomas have been described in Q fever; in viral infections such
      as cytomegalovirus, Epstein-Barr virus, and hepatitis A virus; and in other
      conditions. We submit the first reported case of fibrin ring granuloma in a
      patient with chronic hepatitis C infection, in whom other potential etiologies
      have been excluded, and offer a brief review of available literature on the
      pathogenesis of both conditions.

PMID- 17520521
TI  - Gypenosides induce apoptosis in human hepatoma Huh-7 cells through a
      calcium/reactive oxygen species-dependent mitochondrial pathway.
AB  - We have previously reported that gypenosides induce apoptosis in human
      hepatocarcinoma Huh-7 cells through a mitochondria-dependent caspase-9 activation
      cascade. In order to further explore the critical events leading to apoptosis in
      gypenosides-treated cells, the following effects of gypenosides on components of
      the mitochondrial apoptotic pathway were examined: generation of reactive oxygen
      species (ROS), alteration of the mitochondrial membrane potential (MPT), and the
      subcellular distribution of Bcl-2 and Bax. We show that gypenosides-induced
      apoptosis was accompanied by the generation of intracellular ROS, disruption of
      MPT, and inactivation of ERK, as well as an increase in mitochondrial Bax and a
      decrease of mitochondrial Bcl-2 levels. Ectopic expression of Bcl-2 or treatment
      with furosemide attenuated gypenosides-triggered apoptosis. Treatment with ATA
      caused a drastic prevention of apoptosis and the gypenosides-mediated
      mitochondrial Bcl-2 decrease and Bax increase, but failed to inhibit ROS
      generation and MPT dysfunction. Incubation with antioxidants significantly
      inhibited gypenosides-mediated ROS generation, ERK inactivation, MPT and
      apoptosis. Moreover, an increase of the intracellular calcium ion (Ca(2+))
      concentration rapidly occurred in gypenosides-treated Huh-7 cells. Buffering of
      the intracellular Ca(2+) increase with a Ca(2+) chelator BAMTA/AM blocked the
      gypenosides-elicited ERK inactivation, ROS generation, Bcl-2/Bax redistribution,
      mitochondrial dysfunction, and apoptosis. Based on these results, we propose that
      the rise in intracellular Ca(2+) concentration plays a pivotal role in the
      initiation of gypenosides-triggered apoptotic death.

PMID- 17520522
TI  - Studies on antiproliferative effects of phthalides from Ligusticum chuanxiong in
      hepatic stellate cells.
AB  - Suppression of hepatic stellate cell (HSC) growth and activation, and induction
      of apoptosis, have been proposed as therapeutic strategies for the treatment and
      prevention of liver fibrosis. Our previous study showed that the Chinese herb
      Ligusticum chuanxiong (LC) inhibits platelet-derived growth factor (PDGF-BB)
      induced HSC proliferation. The present study was designed to investigate the
      active principles and their action mechanisms. With a bioactivity-directed
      fractionation approach, DNA synthesis (bromodeoxyuridine (BrdU) incorporation),
      cell cycle related proteins and apoptosis markers were determined to evaluate the
      inhibitory effects of active principles of LC. Two phthalides, Z,Z'-6,8',7,3'
      diligustilide (1) and levistolide A (2), from LC significantly abrogated PDGF-BB
      induced proliferation in both rat and human HSC lines. These inhibitory effects
      of compounds 1 and 2 were associated with reduction of alpha-smooth muscle actin
      and collagen expressions. The cell cycle promoting proteins, cyclins D1, D2, E, A
      and B1, were downregulated while the inhibitory proteins p21 and 27 were up
      regulated. JNK phosphorylation was up-regulated by compounds 1 and 2. In HSC-T6,
      the two compounds induced apoptosis through the activation of caspases 9 and 3,
      increase in cytosolic cytochrome c release, and downregulation of Bcl-2 and Akt
      phosphorylation. Moreover, neither phthalides caused direct cytotoxicity to
      either HSCs or rat primary hepatocytes under experimental concentrations. These
      results indicate that two phthalides from LC inhibited PDGF-BB-activated HSC
      proliferation possibly through cell cycle inhibition and apoptosis mechanisms.
      They might be potential anti-fibrotic drugs for the treatment and prevention of
      hepatic fibrosis.

PMID- 17520523
TI  - Novel epoxyfuranoid lignans and antitubercular constituents from the leaves of
      Beilschmiedia tsangii.
AB  - Three new epoxyfuranoid lignans, 4alpha,5alpha-epoxybeilschmin A (1),
      4alpha,5alpha-epoxybeilschmin B (2), and beilschmin D (3), together with nine
      known compounds have been isolated from the leaves of Beilschmiedia tsangii. The
      structures of these new compounds were determined through spectral analyses.
      Among the isolates, beilschmin A (4) and beilschmin B (5) exhibited potent
      antitubercular activities (MICs = 2.5 and 7.5 microg/mL, respectively) against
      Mycobacterium tuberculosis 90 - 221387 in vitro.

PMID- 17520524
TI  - Phenolic constituents in dried flowers of aloe vera (Aloe barbadensis) and their
      in vitro antioxidative capacity.
AB  - The dried flowers from Aloe vera (L.) Burm. f. (Aloe barbadensis Mill.)
      (Asphodelaceae) were analysed by means of HPLC-DAD and HPLC-MS/MS, verifying
      chlorogenic, caffeic, 5-P-coumaroylquinic, caffeoylshikimic, 5-feruloylquinic, 5
      P-CIS-coumaroylquinic, P-coumaric and ferulic acid as well as luteolin, apigenin,
      quercetin, kaempferol, isoorientin, isovitexin and their 7-O-glucosides,
      saponarin and lutonarin. On searching for anthranoids in the flower extract, aloe
      emodin as well as the glycosylchromone aloeresin B could be identified. Aloin A
      and B, the laxative principle of the drug Curacao-Aloes, are not accumulated in
      the dried flowers. The polyphenol content of three different batches was 0.73 -
      1.01% (+/- 0.05%) and the flavonoid content 0.24 - 0.34% (+/- 0.01%). The
      hydrophilic antioxidative capacity amounted to 85.7 - 94.9 (+/- 0.5) micromol
      TEAC/g dried Aloe vera flower and was directly correlated with the polyphenol and
      flavonoid contents.

PMID- 17520525
TI  - A bioactive polyacetylene compound isolated from Centella asiatica.
AB  - A polyacetylene compound was isolated from the aerial parts of Centella asiatica.
      The chemical structure of this new compound was identified as methyl 5-[(E)-9
      hydroxy-1-(1-hydroxyhexyl)-2-methoxyundeca-3,10-diene-5,7-diynyloxy]pentanoate
      (cadiyenol). This compound induces apoptosis (63%) independent of cell cycle
      regimen in mouse lymphoma cells (P388D1) at 28 microM (IC (50) = 24 +/- 2 microM)
      in 24 hours. The compound also reduces nitric oxide production by 70 +/- 2% in
      lipopolysacharride-activated mouse macrophages at 24 microM with no measurable
      cytotoxicity.

PMID- 17520526
TI  - [Remembering - working through - bringing together - the relationship between
      psychosomatic medicine and psychiatry].

PMID- 17520527
TI  - [For and against: does sponsoring impede the growth of knowledge in medicine?].

PMID- 17520528
TI  - [Is the schizophrenia diagnosis still appropriate?].
AB  - To analyse what psychotic, depressive and manic syndromes have in common and what
      separates them, we compared 130 population-based first-admission cases of
      schizophrenia and depression from illness onset until first admission and 130
      "healthy" controls. We also studied 107 first-episode cases of schizophrenia over
      11.2 years. Illness onset in depression and schizophrenia is marked by identical
      symptoms, mostly depressive in type. Throughout the course of schizophrenia
      depression is the most frequent symptom. Psychosis risk increases when depressive
      and anxiety symptoms increase and decreases when these symptoms decrease. The
      depressive syndrome is an integral part of schizophrenia. Schizophrenia diagnosis
      should be replaced by a four-dimensional construct, with each dimension
      associated with a mainly specific indication for therapy.

PMID- 17520529
TI  - [Therapy and assessment of psychological trauma as mirrored by fiction - part 4:
      popularizing and trivializing trauma in the present time].

PMID- 17520532
TI  - [Announcement of the Gerd Huber Prize for research work on the prevention of
      Psychosis].

PMID- 17520533
TI  - [Recommendations for background studies in tuberculosis].

PMID- 17520534
TI  - Impact of different methods of feedback to clinicians after postprescription
      antimicrobial review based on the Centers For Disease Control and Prevention's 12
      Steps to Prevent Antimicrobial Resistance Among Hospitalized Adults.
AB  - OBJECTIVES: To evaluate (1) the framework of the 12 Steps to Prevent
      Antimicrobial Resistance Among Hospitalized Adults that is part of the Centers
      for Disease Control and Prevention (CDC) Campaign to Prevent Antimicrobial
      Resistance in Healthcare Settings, with regard to steps addressing antimicrobial
      use; and (2) methods of feedback to clinicians regarding antimicrobial use after
      postprescription review. DESIGN: Prospective intervention to identify and modify
      inappropriate antimicrobial therapy. SETTING: A 1,000-bed, tertiary care teaching
      hospital. PATIENTS: Inpatients in selected medicine and surgery units receiving
      broad-spectrum antimicrobials for 48-72 hours. INTERVENTIONS: We created a
      computer-based clinical-event detection system that automatically identified
      inpatients taking broad-spectrum and "reserve" antimicrobials for 48-72 hours.
      Although prior approval was required for initial administration of broad-spectrum
      and reserve antimicrobials, once approval was obtained, therapy with the
      antimicrobials could be continued indefinitely at the discretion of the treating
      clinician. Therapy that was ongoing at 48-72 hours was reviewed by an infectious
      diseases pharmacist or physician, and when indicated feedback was provided to
      clinicians to modify or discontinue therapy. Feedback was provided via a direct
      telephone call, a note on the front of the medical record, or text message sent
      to the clinician's pager. The acceptance rate of feedback was recorded and
      recommendations were categorized according to the 12 steps recommended by the
      CDC. RESULTS: Interventions were recommended for 334 (30%) of 1,104 courses of
      antimicrobial therapy reviewed. A total of 87% of interventions fit into one of
      the CDC's 12 steps of prevention: 39% into step 3 ("target the pathogen"), 1%
      into step 4 ("access experts"), 3% into steps 7 and 8 ("treat infection, not
      colonization or contamination"), 18% into step 9 ("say ;no' to vancomycin"), and
      26% into step 10 ("stop treatment when no infection"). The rate of compliance
      with recommendations to improve antimicrobial use was 72%. No differences in
      compliance were seen with the different methods of feedback. CONCLUSIONS: Nearly
      one-third of antimicrobial courses did not follow the CDC's recommended 12 steps
      for prevention of antimicrobial resistance. Clinicians demonstrated high
      compliance with following suggestions made after postprescription review,
      suggesting that it is a useful approach to decreasing and improving antimicrobial
      use among inpatients.

PMID- 17520535
TI  - Impact of different methods for describing the extent of prior antibiotic
      exposure on the association between antibiotic use and antibiotic-resistant
      infection.
AB  - OBJECTIVE: Many studies have investigated the association between prior
      antibiotic use and antibiotic resistance. However, methods used in past studies
      to describe the extent of prior antibiotic use (eg, use of the 2 categories
      exposure versus no exposure and measurement of duration of exposure) have not
      been reviewed. The impact of the use of different methods for quantifying the use
      of antibiotics is unknown. The objectives of this study were to characterize past
      approaches to describing the extent of antibiotic use and to identify the impact
      of the use of different methods on associations between use of specific
      antibiotics and infection with an antibiotic-resistant-organism. METHODS: We
      conducted a systematic review of studies that investigated risk factors for
      extended-spectrum beta -lactamase (ESBL)-producing Escherichia coli and
      Klebsiella species to identify variability in past approaches to describing the
      extent of antibiotic use. We then reanalyzed a data set from a prior study of
      risk factors for infection with ESBL-producing E. coli and Klebsiella species. We
      developed 2 separate multivariable models: 1 in which prior antibiotic use was
      described as a categorical variable (eg, exposure or no exposure) and 1 in which
      antibiotic use was described as a continuous variable (eg, measured in antibiotic
      days). These models were compared qualitatively. SETTING: Large academic medical
      center. RESULTS: The 25 articles included in the systematic review revealed a
      variety of methods used to describe the extent of prior antibiotic exposure. Only
      1 study justified its approach. Results from the 2 multivariable models that used
      different methodologic approaches differed substantially. Specifically, use of
      third-generation cephalosporins was a risk factor for infection with ESBL
      producing E. coli and Klebsiella species when antibiotic use was described as a
      continuous variable but not when antibiotic use was described as a categorical
      variable. CONCLUSIONS: There has been no consistent method for assessing the
      extent of prior antibiotic exposure. The use of different methods may
      substantially alter the identified antimicrobial risk factors, which has
      important implications for the resultant interventions regarding antimicrobial
      use.

PMID- 17520536
TI  - Increase in the rate of sternal surgical site infection after coronary artery
      bypass graft: a marker of higher severity of illness.
AB  - OBJECTIVE: To evaluate factors related to a gradual rise in sternal surgical site
      infection (SSI) rates. DESIGN: Retrospective cohort study. SETTING: A 608-bed,
      tertiary care teaching hospital. PATIENTS: All patients who underwent coronary
      artery bypass graft (CABG) from January 2000 through September 2004. RESULTS: Of
      3,578 patients who underwent CABG, 144 (4%) had sternal SSI. There was an
      increase in infection rate, with a marked reduction in the number of operations
      per year. The percentage of patients with peripheral vascular disease increased
      from 12% to 24.3% (P<.001), and the percentage with congestive heart failure
      increased from 17% to 22% (P<.001). Between 2002 and 2004, the mean duration of
      surgery increased from 233 to 290 minutes (P<.001), the percentage of patients
      with a National Nosocomial Infections Surveillance System (NNIS) risk index of 2
      increased from 14.3% to 38% (P<.001), and the percentage of patients with a
      postoperative stay in the intensive care unit of greater than 72 hours increased
      from 29% to 40.6% (P<.001). Multivariate analysis showed diabetes mellitus,
      peripheral vascular disease, obesity, duration of surgery, and postoperative stay
      in the intensive care unit of greater than 72 hours to be independently
      associated with infection. CONCLUSIONS: An increase in infection in the CABG
      population not associated with an outbreak may be a reflection of a change in the
      severity of illness. Preoperative, intraoperative, and postoperative markers for
      increased infection risk may be used, in addition to the NNIS risk index, to
      assess the patient population risk.

PMID- 17520537
TI  - Exposure to pulmonary tuberculosis in a neonatal intensive care unit: unique
      aspects of contact investigation and management of hospitalized neonates.
AB  - OBJECTIVE: We describe the investigation of a tuberculosis (TB) exposure in which
      a neonatal intensive care unit (NICU) respiratory therapist was the index
      patient, as well as the rationale by which exposed infants were managed and
      possible explanations for the lack of transmission to these patients. DESIGN:
      Description of an exposure investigation. SETTING: Academic, level IV NICU of a
      tertiary care children's hospital. PARTICIPANTS: Contacts of a respiratory
      therapist with pulmonary TB disease, including household members, healthcare
      coworkers, and infant patients. RESULTS: In addition to 5 household contacts, 248
      healthcare coworkers and 180 infant patients were identified as possibly exposed
      during the 24 days that the index patient worked between December 3, 2004, and
      January 30, 2005. Tuberculin skin tests (TSTs) were performed for 233 of the 235
      contacts with the greatest degree of exposure (household and coworker contacts)
      who had a previously documented negative TST result or whose TST status was
      unknown prior to the investigation. No cases of latent tuberculosis infection or
      TB disease were identified. Because of characteristics of the index case, the
      exposure duration and setting, the infants' small lung volumes, and lack of
      evidence of transmission to higher-risk contacts, infants were not clinically
      evaluated or empirically treated for TB disease. Surveillance for subsequent
      illness was carried out by primary healthcare providers and parents. No TB
      disease or unexplained illness in these infants was reported in the 20 months
      following the exposure. CONCLUSION: After limited hospital exposure to a
      healthcare worker with pulmonary TB disease who is not highly contagious,
      neonates can be safely managed without specific evaluation for TB disease or
      empirical treatment.

PMID- 17520538
TI  - Value of performing active surveillance cultures on intensive care unit discharge
      for detection of methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: To quantify the value of performing active surveillance cultures for
      detection of methicillin-resistant Staphylococcus aureus (MRSA) on intensive care
      unit (ICU) discharge. DESIGN: Prospective cohort study. SETTING: Medical ICU
      (MICU) and surgical ICU (SICU) of a tertiary care hospital. PARTICIPANTS: We
      analyzed data on adult patients who were admitted to the MICU or SICU between
      January 17, 2001, and December 31, 2004. All participants had a length of ICU
      stay of at least 48 hours and had surveillance cultures of anterior nares
      specimens performed on ICU admission and discharge. Patients who had MRSA
      positive clinical cultures in the ICU were excluded. RESULTS: Of 2,918 eligible
      patients, 178 (6%) were colonized with MRSA on ICU admission, and 65 (2%)
      acquired MRSA in the ICU and were identified by results of discharge surveillance
      cultures. Patients with MRSA colonization confirmed by results of discharge
      cultures spent 853 days in non-ICU wards after ICU discharge, which represented
      27% of the total number of MRSA colonization-days during hospitalization in non
      ICU wards for patients discharged from the ICU. CONCLUSIONS: Surveillance
      cultures of nares specimens collected at ICU discharge identified a large
      percentage of MRSA-colonized patients who would not have been identified on the
      basis of results of clinical cultures or admission surveillance cultures alone.
      Furthermore, these patients were responsible for a large percentage of the total
      number of MRSA colonization-days during hospitalization in non-ICU wards for
      patients discharged from the ICU.

PMID- 17520539
TI  - Epidemiology and genetic diversity of methicillin-resistant Staphylococcus aureus
      strains in residential care homes for elderly persons in Hong Kong.
AB  - OBJECTIVE: To determine the prevalence and molecular epidemiology of methicillin
      resistant Staphylococcus aureus (MRSA) strains among residents in residential
      care homes for the elderly in Hong Kong. DESIGN: Cross-sectional and descriptive
      study. PARTICIPANTS: A total of 949 residents in 13 residential care homes for
      elderly persons in Hong Kong in January 2005. METHODS: MRSA colonization was
      assessed by culture of swab specimens from anterior nares and active skin
      lesions. Characteristics of residents were obtained by a standard questionnaire.
      All MRSA isolates were analyzed by polymerase chain reaction for their
      staphylococcal cassette chromosome (SCC) mec content and were typed by pulsed
      field gel electrophoresis (PFGE) and multilocus sequencing. RESULTS: MRSA
      colonization was detected in 27 residents (2.8%). No MRSA was found in 2
      facilities. The rate of MRSA carriage in the other 11 facilities ranged from 1.9%
      to 4.2%. In univariate analysis, functional immobility (odds ratio [OR], 1.4),
      history of hospital admission (OR, 2.3), and the use of nebulized medication (OR,
      5.4) were significantly associated with MRSA colonization. The isolates had 11
      unique antibiograms, with 14 isolates susceptible to all but 1 or 2 of the non-
      beta -lactam antimicrobial agents tested. The isolates exhibited SCCmec types I
      (1 isolate), II (2 isolates), III (1 isolate), IV/IVA (10 isolates), and V (13
      isolates). No isolates had the Panton-Valentine leukocidin genes. PFGE analysis
      clustered all except 1 isolate into 7 PFGE types, designated HKU10 to HKU70.
      Between 1 and 4 unique PFGE types were found in the individual residential care
      facilities. CONCLUSION: This study documented the emergence of SCCmec types IV
      and V among genetically diverse MRSA strains in residential care homes for
      elderly persons in Hong Kong.

PMID- 17520540
TI  - Eradication of amebiasis in a large institution for adults with mental
      retardation in Taiwan.
AB  - OBJECTIVE: Investigation of a program to eradicate amebiasis using consecutive
      intensive mass screenings followed by medication in a large institute for adults
      with mental retardation in Taiwan. DESIGN: Prospective cohort study, with 3 years
      of follow-up. SETTING: A large, 450-bed institution for adults with mental
      retardation located in southern Taiwan. PARTICIPANTS: All 443 adults with mental
      retardation in the institution, who have various motor and/or mental handicaps,
      were included in this study. INTERVENTIONS: A total of 7 consecutive intensive
      mass screenings for amebiasis for all residents (performed in March, August and
      November 2001, March and August 2002, January 2003, and May 2004). Infected
      patients were treated using the standard protocol of the Center for Disease
      Control of Taiwan. RESULTS: Enzyme immunoassay testing was used for the amebiasis
      screening, with the rapid detection of the specific antigen for Entamoeba
      histolytica in human fecal specimens confirmed by microscopic examination. The
      serial prevalence and cumulative incidence were then calculated. The prevalence
      of amebic infection declined in serial screenings, but new infections and
      reinfections were detected in 5 of 6 follow-up screenings. The prevalence was
      10.8% at the beginning of the program and then gradually reduced, falling to
      6.3%, 3.6%, 2.7%, 3.4%, and 2.2%. Finally, no more positive cases were identified
      in the last screening (May 2004). The cumulative incidence rate stabilized at
      around 40% by the fifth screening. Of the 179 infected patients, 120 had primary
      infections, with 59 cases of multiple amebic infections. CONCLUSIONS: Active
      surveillance with intensive mass screening is an effective method of identifying
      asymptomatic and latent cases of amebiasis in areas where it is endemic, such as
      an institution for adults with mental retardation.

PMID- 17520541
TI  - Increased rate of catheter-related bloodstream infection associated with use of a
      needleless mechanical valve device at a long-term acute care hospital.
AB  - OBJECTIVE: To determine whether introduction of a needleless mechanical valve
      device (NMVD) at a long-term acute care hospital was associated with an increased
      frequency of catheter-related bloodstream infection (BSI). DESIGN: For patients
      with a central venous catheter in place, the catheter-related BSI rate during the
      24-month period before introduction of the NMVD, a period in which a needleless
      split-septum device (NSSD) was being used (hereafter, the NSSD period), was
      compared with the catheter-related BSI rate during the 24-month period after
      introduction of the NMVD (hereafter, the NMVD period). The microbiological
      characteristics of catheter-related BSIs during each period were also compared.
      Comparisons and calculations of relative risks (RRs) with 95% confidence
      intervals (CIs) were performed using chi (2) analysis. RESULTS: Eighty-six
      catheter-related BSIs (3.86 infections per 1,000 catheter-days) occurred during
      the study period. The rate of catheter-related BSI during the NMVD period was
      significantly higher than that during the NSSD period (5.95 vs 1.79 infections
      per 1,000 catheter-days; RR, 3.32 [95% CI, 2.88-3.83]; P<.001). A significantly
      greater percentage of catheter-related BSIs during the NMVD period were caused by
      gram-negative organisms, compared with the percentage recorded during the NSSD
      period (39.5% vs 8%; P=.007). Among catheter-related BSIs due to gram-positive
      organisms, the percentage caused by enterococci was significantly greater during
      the NMVD period, compared with the NSSD period (54.8% vs 13.6%; P=.004). The
      catheter-related BSI rate remained high during the NMVD period despite several
      educational sessions regarding proper use of the NMVD. CONCLUSIONS: An increased
      catheter-related BSI rate was temporally associated with use of a NMVD at the
      study hospital, despite several educational sessions regarding proper NMVD use.
      The current design of the NMVD may be unsafe for use in certain patient
      populations.

PMID- 17520542
TI  - Effect of education on the rate of and the understanding of risk factors for
      intravascular catheter-related infections.
AB  - OBJECTIVE: Intravascular catheters are indispensable tools in modern medical
      therapy. In spite of their great benefits, however, the widespread use of
      catheters leads to several complications, including infections that cause
      significant morbidity, mortality, and economic losses for hospitalized patients.
      DESIGN: This study was conducted at Farabi Hospital, a 495-bed facility at
      Karadeniz Technical University Medical School in Trabzon, Turkey, and involved 3
      separate periods: preeducation, education, and posteducation. Patients with
      intravascular catheters were monitored daily, as were the results of their
      physical examinations. The information acquired was recorded in a questionnaire.
      RESULTS: During the preeducation period (October 2003 through March 2004), 405
      intravascular catheters inserted into 241 patients were observed for 5,445
      catheter-days. Seventy-one cases of intravascular catheter-related infection
      (CRI) were identified, giving a CRI rate of 13.04 infections per 1,000 catheter
      days. The catheter-related bloodstream infection (CRBSI) rate was 8.3 infections
      per 1,000 catheter-days, and the exit-site infection (ESI) rate was 3.5
      infections per 1,000 catheter-days. During the posteducation period (June through
      November 2004), 365 intravascular catheters inserted into 193 patients were
      observed for 5,940 catheter-days. Forty-five cases of CRI were identified, giving
      a rate of 7.6 infections per 1,000 catheter-days. The CRBSI rate was 4.7
      infections per 1,000 catheter-days, and the ESI rate was 2.2 infections per 1,000
      catheter-days. When findings from the 2 periods were compared, it was determined
      that education reduced CRI incidence by 41.7%. CONCLUSION: CRI can be prevented
      when hospital personnel are well informed about these infections. We compared the
      knowledge levels of the relevant personnel in our hospital before and after
      theoretical and practical training and identified a significant increase in
      knowledge after training (P<.0001). Parallel to this, although still below ideal
      levels, we identified a significant improvement in the incidence of CRI during
      the posteducation period (P=.004). The rate was low for the first 3 months of
      this period but increased 2.08 times after the third month. In conclusion,
      regular training for the residents in charge of inserting intravascular catheters
      and the nurses and interns who maintain the catheters is highly effective in
      reducing the rate of CRI in large teaching hospitals.

PMID- 17520543
TI  - Assessment of adverse events associated with antiretroviral regimens for
      postexposure prophylaxis for occupational and nonoccupational exposures to
      prevent transmission of human immunodeficiency virus.
AB  - OBJECTIVE: To assess adverse events associated with antiretroviral regimens for
      human immunodeficiency virus (HIV) postexposure prophylaxis (PEP), with a
      particular focus on the treatment combination of zidovudine, lamivudine, and
      tenofovir (ZDV-3TC-TDF). METHODS: Retrospective chart review for individuals who
      received HIV PEP for occupational and nonoccupational exposure, and multivariate
      analyses to identify risk factors for noncompletion of PEP and adverse events
      associated with PEP. SETTING: University of Rochester Health Service Occupational
      Health Program and University of Rochester AIDS Center. PARTICIPANTS: Healthcare
      workers who received HIV PEP for occupational exposure from January 1, 1999, to
      December 31, 2004, and individuals who received HIV PEP for nonoccupational
      exposure from January 1, 2002, to December 31, 2004.Results. We found increased
      rates of nausea among subjects who received treatment with ZDV-3TC-TDF and
      subjects who received treatment with zidovudine, lamivudine, and indinavir (ZDV
      3TC-IDV). Analyses showed that female sex was a risk factor for nausea. Compared
      with subjects who received treatment with ZDV-3TC-TDF, subjects who received
      treatment with ZDV-3TC-IDV were less likely to not complete the HIV PEP for
      occupational exposure. CONCLUSION: Preventive treatment of adverse events may be
      necessary to ensure completion of HIV PEP.

PMID- 17520544
TI  - Risk of transmission associated with live attenuated vaccines given to healthy
      persons caring for or residing with an immunocompromised patient.
AB  - OBJECTIVE: Persons who receive live attenuated vaccine may occasionally transmit
      the vaccine strain to others. The risk of such transmission is a concern,
      especially for persons who provide care to immunocompromised patients (ie, family
      and healthcare workers [HCWs]). Since the Advisory Committee on Immunization
      Practices released guidelines 10 years ago, several new live attenuated products
      have been introduced, and additional information on older vaccines has become
      available. To better define the risk of transmission associated with live
      vaccines, we reviewed the currently available literature. RESULTS: A review of
      the medical literature revealed no major risk of transmission associated with any
      live attenuated vaccine. A theoretical risk continues to exist for the live
      attenuated intranasal influenza vaccine and the smallpox vaccine. CONCLUSIONS:
      The available data support routine vaccination with live attenuated vaccines for
      all household contacts of immunocompromised patients and for HCWs caring for such
      patients. The benefit for immunocompromised patients of providing herd immunity
      against this group of potentially devastating pathogens outweighs the risk, if
      any, of secondary transmission.

PMID- 17520545
TI  - Impact of Bordetella pertussis exposures on a Massachusetts tertiary care medical
      system.
AB  - OBJECTIVE: To assess the impact of outbreaks of Bordetella pertussis infection on
      a tertiary care medical system. DESIGN: Retrospective study. SETTING: Academic
      tertiary care medical center and affiliated ambulatory care settings. SUBJECTS:
      All patients and healthcare workers (HCWs) who were in close contact with
      patients with laboratory-confirmed cases of B. pertussis infection from October
      1, 2003, through September 30, 2004. INTERVENTION: Direct and indirect medical
      center costs were determined, including low and high estimates of time expended
      in the evaluation and management of exposed patients and HCWs during outbreak
      investigations of laboratory-confirmed cases of B. pertussis infection. RESULTS:
      During this period, 20 primary and 3 secondary laboratory-confirmed cases of B.
      pertussis infection occurred, with 2 primary pertussis cases and 1 secondary case
      occurring in HCWs. Outbreak investigations prompted screening of 353 medical
      center employees. Probable or definitive exposure was identified for 296 HCWs,
      and 287 subsequently received treatment or prophylaxis for B. pertussis
      infection. Direct medical center costs for treatment and prophylaxis were $13,416
      and costs for personnel time were $19,500-$31,190. Indirect medical center costs
      for time lost from work were $51,300-$52,300. The total cost of these
      investigations was estimated to be $85,066-$98,456. CONCLUSIONS: Frequent B.
      pertussis exposures had a major impact on our facility. Given the impact of
      exposures on healthcare institutions, routine vaccination for HCWs may be
      beneficial.

PMID- 17520546
TI  - Clinical and economic impact of multidrug resistance in nosocomial Acinetobacter
      baumannii bacteremia.
AB  - OBJECTIVE: To investigate the impact of antimicrobial resistance on clinical and
      economic outcomes among hospitalized patients with multidrug-resistant (MDR)
      Acinetobacter baumannii bacteremia. DESIGN: A retrospective, matched-cohort
      study. SETTING: A tertiary care university teaching hospital. METHODS: A matched
      case-control (1 : 1) study was conducted to compare the differences in clinical
      and economic outcomes of patients with MDR A. baumannii bacteremia and patients
      with non-MDR A. baumannii bacteremia. Case patients were matched to control
      patients on the basis of sex, age, severity of underlying and acute illness, and
      length of hospital stay before onset of bacteremia. RESULTS: Forty-six (95.8%) of
      48 cases with MDR A. baumannii bacteremia were eligible for the study and matched
      with appropriate controls. The sepsis-related mortality rate was 34.8% among
      cases and 13.0% among controls, for an attributable mortality rate of 21.8%
      (adjusted odds ratio, 4.1 [95% confidence interval, 1.1-15.7]; P=.036). After the
      onset of bacteremia, cases and controls had a significantly different length of
      hospital stay (54.2 vs 34.1 days; P=.006), hospitalization cost (US$9,349 vs
      US$4,865; P=.001), and antibiotic therapy cost (US$2,257 vs US$1,610; P=.014).
      Thus, bacteremia due to MDR A. baumannii resulted in 13.4 days of additional
      hospitalization and US$3,758 of additional costs, compared with bacteremia due to
      non-MDR A. baumannii. CONCLUSIONS: Patients with MDR A. baumannii bacteremia had
      a higher mortality rate and incurred greater medical costs than patients with non
      MDR A. baumannii bacteremia.

PMID- 17520547
TI  - Acinetobacter skin carriage among US army soldiers deployed in Iraq.
AB  - Skin carriage of Acinetobacter calcoaceticus-baumannii complex was not detected
      among a representative sample of 102 US Army soldiers stationed in Iraq. This
      observation refutes the hypothesis that preinjury skin carriage serves as the
      reservoir for the Acinetobacter infections seen in US military combat casualties.

PMID- 17520548
TI  - Importation of Acinetobacter baumannii into a burn unit: a recurrent outbreak of
      infection associated with widespread environmental contamination.
AB  - A burn patient was infected with Acinetobacter baumannii on transfer to the
      hospital after a terrorist attack. Two patients experienced cross-infection.
      Environmental swab samples were negative for A. baumannii. Six months later, the
      bacteria reemerged in 6 patients. Environmental swab samples obtained at this
      time were inoculated into a minimal mineral broth, and culture results showed
      widespread contamination. No case of infection occurred after closure of the unit
      for disinfection.

PMID- 17520549
TI  - Colonization with multidrug-resistant organisms in evacuees after Hurricane
      Katrina.
AB  - After Hurricane Katrina, 50 patients were evacuated to Grady Memorial Hospital in
      Atlanta, Georgia, with limited medical records. The infection control department
      ordered contact precautions for 16 patients. Surveillance cultures performed on
      admission identified colonization with multidrug-resistant (MDR) bacteria in 9
      patients (18%). Presence of a wound was the strongest predictor for MDR
      colonization. More data are needed to reliably predict MDR bacterial
      colonization.

PMID- 17520550
TI  - Evaluation of the microbiology of soft-tissue abscesses in the era of community
      associated strains of methicillin-resistant Staphylococcus aureus: an argument
      for empirical contact precautions.
AB  - To ascertain the microbiology of skin abscesses, emergency department records
      were reviewed to identify patients with debrided skin abscesses. Methicillin
      resistant Staphylococcus aureus was isolated from 255 (67.6%) of 377 culture
      samples from episodes in the adult cohort and from 145 (79.7%) of 182 culture
      samples from episodes in the pediatric cohort. Thus, empirical use of contact
      precautions for patients with skin abscesses should be strongly considered.

PMID- 17520551
TI  - Acquisition of methicillin-resistant Staphylococcus aureus in the acute care
      setting: incidence and risk factors.
AB  - Our objective was to assess the incidence of and risk factors for methicillin
      resistant Staphylococcus aureus (MRSA) acquisition among patients in acute care
      wards. For 5 months, patients were screened for MRSA colonization at admission
      and at discharge. At admission, 6.6% of patients had cultures positive for MRSA,
      and 3.1% of patients who had tested negative for MRSA on admission had cultures
      positive for MRSA at discharge. Only the presence of chronic skin breaks at
      admission was independently associated with MRSA acquisition.

PMID- 17520552
TI  - Nasal carriage of Staphylococcus aureus: which sequence types do orthopedic
      surgical healthcare workers carry?
AB  - Using sequence typing methods, we found that healthcare workers on our orthopedic
      surgery unit were persistent carriers of a limited number of sequence types of
      Staphylococcus aureus for a limited time. Multilocus sequence typing
      characterized 3 clonal complexes that accounted for more than 80% of the clonal
      complexes identified.

PMID- 17520553
TI  - Risk of nosocomial transmission of Nipah virus in a Bangladesh hospital.
AB  - We conducted a seroprevalence study and exposure survey of healthcare workers to
      assess the risk of nosocomial transmission of Nipah virus during an outbreak in
      Bangladesh in 2004. No evidence of recent Nipah virus infection was detected
      despite substantial exposures and minimal use of personal protective equipment.

PMID- 17520554
TI  - A cluster of hemodialysis-related bacteremia linked to artificial fingernails.
AB  - We examined a cluster of 5 hemodialysis patients who contracted gram-negative
      bacteremia. A nurse who used an artificial fingernail to open a vial of heparin
      that was mixed to make a flush solution had a culture of an artificial fingernail
      specimen positive for Serratia marcescens. The typing of the S. marcescens
      strains isolated from the 5 patients and the nurse showed them to be identical.
      This finding provides strong support for policies prohibiting artificial nails
      for healthcare workers in all hemodialysis units.

PMID- 17520555
TI  - Hand rub-associated fire incidents during 25,038 hospital-years in Germany.
AB  - Fire incidents in German hospitals related to the use of alcohol-based hand rubs
      were analyzed. Seven nonsevere fire incidents were identified, occurring during
      25,038 hospital-years, which were caused by individual human actions and not by
      technical failure. The results underline the safety of using alcohol-based hand
      rubs in hospitals.

PMID- 17520556
TI  - Nurses' intentions to wear gloves during venipuncture procedures: a behavioral
      psychology perspective.
AB  - Registered nurses working at a teaching hospital in Kuwait were surveyed to
      assess the psychosocial variables associated with their intention to comply with
      glove-wearing recommendations. Perceived consequences and normative beliefs, as
      well as sex and years of nursing experience, significantly influenced their
      behavioral intentions, suggesting that improvements in intention to comply are
      more likely to come from practical demonstrations that show nurses the potential
      outcomes of both using and not using gloves.

PMID- 17520557
TI  - Use of the Haddon matrix as a tool for assessing risk factors for sharps injury
      in emergency departments in the United Arab Emirates.
AB  - We investigated the epidemiology and prevention of sharps injuries in the United
      Arab Emirates. Among 82 emergency nurses and 38 doctors who responded to our
      questionnaire, risk factors for sharp device injuries identified using the Haddon
      matrix included personal factors (for the pre-event phase, a lack of infection
      control training, a lack of immunization, and recapping needles, and for the
      postevent phase, underreporting of sharps injuries) and equipment-related factors
      (for the pre-event phase, failure to use safe devices; for the event phase,
      failure to use gloves in all appropriate situations). Nearly all injuries to
      doctors were caused by suture needles, and among nurses more than 50% of injuries
      were caused by hollow-bore needles.

PMID- 17520558
TI  - Contamination of peripheral hematopoeitic stem cell products with a Mycobacterium
      mucogenicum-related pathogen.
AB  - A gram-positive rod with a restriction pattern closely related to the published
      nucleotide sequence of Mycobacterium mucogenicum was isolated from 6 of 45 units
      of peripheral blood stem cell products. The source of the contamination was
      traced to ice cubes used in processing the peripheral blood stem cell products.
      Substituting reusable ice trays for ice from an ice machine terminated the
      outbreak.

PMID- 17520559
TI  - Pseudo-outbreak of Bordetella bronchiseptica infection associated with
      contaminated rabbit blood used as a broth culture supplement.
AB  - A cluster of clinical isolates of Bordetella bronchiseptica was identified by
      microbiology laboratory personnel. A clinical and molecular epidemiologic study
      determined that this cluster represented a pseudo-outbreak due to bacterial
      contamination of rabbit blood used as a broth culture supplement. This pseudo
      outbreak highlights the importance of quality assurance programs in the
      laboratory.

PMID- 17520560
TI  - Sharp-device injuries and perceived risk of infection with bloodborne pathogens
      among healthcare workers in rural Kenya.

PMID- 17520561
TI  - Pseudo-outbreak of Ochrobactrum anthropi bacteremia related to cross
      contamination from erythrocyte sedimentation tubes.

PMID- 17520562
TI  - A controlled study of Legionella concentrations in water from faucets with
      aerators or laminar water flow devices.

PMID- 17520563
TI  - CRRT protects the kidney during acute renal failure.

PMID- 17520564
TI  - Patient and kidney survival by dialysis modality in critically ill patients with
      acute kidney injury.
AB  - Using a large, international cohort, we sought to determine the effect of initial
      technique of renal replacement therapy (RRT) on the outcome of acute renal
      failure (ARF) in the intensive care unit (ICU). We enrolled 1218 patients treated
      with continuous RRT (CRRT) or intermittent RRT (IRRT) for ARF in 54 ICUs in 23
      countries. We obtained demographic, biochemical and clinical data and followed
      patients to either death or hospital discharge. Information was analyzed to
      assess the independent impact of treatment choice on survival and renal recovery.
      Patients treated first with CRRT (N=1006, 82.6%) required vasopressor drugs and
      mechanical ventilation more frequently compared to those receiving IRRT (N=212,
      17.4%), (p<0.0001). Unadjusted hospital survival was lower (35.8% vs. 51.9%,
      p<0.0001). However, unadjusted dialysis-independence at hospital discharge was
      higher after CRRT (85.5% vs. 66.2%, p<0.0001). Multivariable logistic regression
      showed that choice of CRRT was not an independent predictor of hospital survival
      or dialysis-free hospital survival. However, the choice of CRRT was a predictor
      of dialysis independence at hospital discharge among survivors (OR: 3.333, 95%
      CI: 1.845 - 6.024, p<0.0001). Further adjustment using a propensity score did not
      significantly change these results. We conclude that worldwide, the choice of
      CRRT as initial therapy is not a predictor of hospital survival or dialysis-free
      hospital survival but is an independent predictor of renal recovery among
      survivors.

PMID- 17520565
TI  - Hyperphosphatemia in dialysis patients: the therapeutic role of lanthanum
      carbonate.
AB  - Phosphate overload is a dramatic consequence in end-stage renal disease (ESRD)
      patients. Recent studies have well documented that abnormalities in mineral and
      bone metabolism in these patients are associated with increased cardiovascular
      morbidity and mortality. Elevated serum phosphate and calcium-phosphate product
      levels play an important role in the pathogenesis of secondary
      hyperparathyroidism and extra-skeletal calcification in dialysis patients.
      Furthermore, inorganic phosphate may cause vascular calcification directly
      through a real ""ossification"" of the tunica media in the vasculature of ESRD
      patients. The ""classical"" treatment of secondary hyperparathyroidism and
      hyperphosphatemia in ESRD patients consists of either calcium- or aluminum-based
      phosphate binders and calcitriol administration. Unfortunately, this ""old
      generation"" therapy is not free of complications. This review paper suggests
      that new calcium- and aluminum-free phosphate binders, such as lanthanum
      carbonate, can be used to treat hyperphosphatemia and secondary
      hyperparathyroidism in ESRD patients.

PMID- 17520566
TI  - A pilot randomized controlled crossover study comparing regional heparinization
      to regional citrate anticoagulation for continuous venovenous hemofiltration.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a regional heparinization and a
      regional citrate method of anticoagulation in CVVH. DESIGN: Randomized controlled
      cross-over study. SUBJECTS: Ten critically ill patients with acute renal failure.
      SETTING: ICU of tertiary hospital. INTERVENTION: CVVH was performed with pre
      filter fluid replacement at 2000 ml/h and a blood flow rate of 150 ml/min.
      Regional heparinization was by the administration of heparin pre-filter at 1500
      IU/h and protamine post-filter at 15 mg/h. Regional citrate anticoagulation was
      by means of a citrate-based replacement fluid (14 mmol/L) administered pre
      dilution. RESULTS: We studied nine males and one female. The mean age and APACHE
      II score were 70.5 and 17 respectively. Median circuit life was 13 hours (IQR
      9.28) for the regional heparinization method compared to 17 hours (IQR 12,19.5)
      for the regional citrate method (p=0.77). There were no episodes of bleeding in
      either group. CONCLUSION: Regional heparinization and regional citrate
      anticoagulation achieve similar circuit life in critically ill patients receiving
      CVVH.

PMID- 17520567
TI  - Treatment of chronic hepatitis B with lamivudine in renal transplant recipients.
AB  - Treatment of chronic hepatitis B in renal transplant recipients remains one of
      the major problems in clinical nephrology. Lamivudine is considered to be a drug
      of choice for these patients, however, its efficacy in patients with hepatitis B
      after renal transplantation (RT) has not been completely proven. Twenty-two RT
      recipients treated with lamivudine were evaluated. The duration of treatment was
      15.6+/-1.9 months. Fourteen patients (64%) had normalization of aminotransferase
      (ALT); in 9 of them (41% of the whole group), serum HBV DNA was eliminated. Serum
      HBeAg was undetectable in 4 out of 15 (27%) previously positive patients. It has
      been statistically proven that the efficacy of lamivudine therapy correlates with
      degree of fibrosis and higher histological activity index values. We could not
      establish any correlation between the outcome of antiviral therapy and patients'
      age, sex, conditions of contagion (while on dialysis or after RT), time lapsed
      after the infection had been detected, duration of post-transplant period, type
      of immunosuppression, HBeAg positivity or negativity, ALT levels, concomitant HCV
      infection. The efficacy of antiviral HBV therapy is limited by the duration of
      lamivudine treatment: in 4 out of 5 patients with virologic response, the viremia
      condition relapsed several weeks after the medication had been stopped. Two
      patients continued to sustain their biochemical response and 1 patient had ALT
      levels elevated to above normal, but the value was almost twice as low as
      initially reported. Liver biopsy was repeated in 4 RT recipients after the end of
      antiviral therapy; in 3 of them positive morphologic changes were observed.

PMID- 17520568
TI  - The relationship between carotid and coronary atherosclerotic damage in dialysis
      patients.
AB  - BACKGROUND: Data relating carotid ultrasound (CU) to atherosclerotic damage
      evaluated by coronary angiography in hemodialysis patients are scarce. METHODS:
      We carried out a cross-sectional study in 33 uremic subjects (age 55 +/- 12
      years, 22 male, 7 diabetic), who have been on dialysis for 41 +/- 48 months
      (range 2-192). Twenty-two underwent a coronary angiography in order to complete
      clinical evaluation for inclusion on the kidney transplantation waiting list, and
      11 because of coronary artery disease (CAD); Gensini's score was calculated.
      Intima-media thickness (IMT) and presence of plaques were related to the degree
      of coronary stenosis and to cardiovascular risk factors. Patients were divided
      into two groups depending on mean IMT (group 1 IM <or= 0.9 mm, n=18; group 2
      IMT>0.9 mm, n=15). RESULTS: Group 2 was older (60 +/- 8 vs 50 +/- 12 year,
      p=0.01), had higher frequency of CAD (53 vs 16%, p=0.02) and had higher
      prevalence of coronary artery stenosis >or= 75% in the right (60 vs 22%, p=0.02),
      left anterior descending (46 vs 16%, p=0.06) and left circumflex coronary
      arteriers (60 vs 11%, p=0.05) than group 1. IMT was not related to the degree of
      CAD evaluated by Gensini's score. IMT sensibility and specificity in detecting
      the presence of hemodynamically significant coronary stenosis were 64% and 68%,
      respectively. Coronary narrowing was correlated with the degree of stenosis of
      common, internal and external carotid arteries (Spearman's rank correlation
      coefficient). During two years of follow-up, six major cardiac events were
      recorded and they were related to Gensini's score. CONCLUSIONS: In uremic
      patients, ultrasonographic evaluation of carotid arteries is a simple,
      noninvasive examination that could be a helpful tool in detecting coronary
      atherosclerotic damage, but IMT does not appear to add more information regarding
      risk stratification of CAD.

PMID- 17520569
TI  - Evaluation of the Polyflux 6H dialyzer in pediatric patients receiving
      maintenance hemodialysis.
AB  - Hemodialysis remains the only life sustaining maintenance renal replacement
      therapy option for children who cannot undergo expeditious renal transplantation
      or who are not medical candidates for peritoneal dialysis. Provision of
      maintenance hemodialysis to small children entails many challenges, which arise
      from the limited choices for appropriately sized disposable dialysis treatment
      components. The dialysis extracorporeal circuit volume, comprised of the blood
      tubing and dialyzer, should be low enough to prevent hypotension and prevent the
      need for repeated blood transfusions. We performed a market acceptance evaluation
      of the Polyflux 6H dialyzer (0.6 m2 membrane surface area; Gambro Renal Products,
      Lakewood, Colorado) in six pediatric patients (3 male, 3 female, mean weight
      24.4+6.5 kg, mean age 10.3+3.8 yrs). We found that the Polyflux 6H Dialyzer
      provided a trend for improved clearance compared to Fresenius F3 and F4
      dialyzers. We found that the Polyflux 6H Dialyzer provided adequate clearance for
      children up to 24 kg in size and is a suitable dialyzer choice for patients 13 to
      26 kg in size.

PMID- 17520571
TI  - Infective endocarditis in hemodialysis patients.

PMID- 17520570
TI  - Prevalence and correlates of anemia and uncontrolled anemia in chronic
      hemodialysis patients--the Campania Dialysis Registry.
AB  - BACKGROUND: This study investigated prevalence and correlates of anemia and
      uncontrolled anemia in chronic hemodialysis patients. METHODS: A cross-sectional
      analysis was performed on registry data for 2,746 chronic (>6 months)
      hemodialysis patients aged 25-84. Data collection included years of dialysis,
      hours of dialysis/wk, disease causing hemodialysis, body mass index (BMI),
      erythropoietin (EPO) treatment, hemoglobin, markers of viral hepatitis, serum
      albumin, calcium, and phosphorus. RESULTS: Prevalence was 88.7% for anemia
      (hemoglobin <11 g/100 mL and EPO treatment at any Hb level), 39.4% for
      uncontrolled anemia (hemoglobin<11 g/100 mL). Gender, years of dialysis,
      hereditary cystic kidney disease (HCKD), and low BMI (<24 kg/m2) were independent
      correlates of anemia (P<0.001). Gender, HCKD, low BMI, serum albumin and calcium
      were independent correlates of uncontrolled anemia (P<0.05). An interaction was
      found between age (not correlated with anemia and uncontrolled anemia) and the
      association of gender with uncontrolled anemia (P<0.05). EPO doses were higher in
      patients with high prevalence of uncontrolled anemia than in patients with low
      prevalence (i.e., women vs men, other diseases vs HCKD, low vs not-low BMI,
      P<0.01). Gender, years of dialysis, HCKD, BMI, serum albumin, and calcium were
      independent correlates of the hemoglobin/EPO dose ratio in patients on EPO
      treatment (P<0.05). CONCLUSION: Anemia and uncontrolled anemia are more frequent
      in hemodialysis patients with shortterm dialysis, diseases other than HCKD, low
      BMI, and female gender. Gender effect was lower in elderly patients. Uncontrolled
      anemia was also associated with low serum albumin and calcium, suggesting that
      these parameters are indices of EPO resistance.

PMID- 17520572
TI  - On-pump vs. off-pump coronary artery bypass surgery at a non-academic community
      hospital: have biocompatibility improvements eliminated the superiority of off
      pump surgery?
AB  - OBJECTIVES: Standard coronary artery bypass grafting (CABG) surgery involves
      cardiopulmonary bypass (CPB) but given concerns over neurological and
      inflammatory complications related to CPB, many patients receive so-called off
      pump procedures (OPCABG). Our objective is to determine if the recent
      improvements in the biocompatibility of CPB circuitry have improved post
      operative outcomes at the community hospital level, particularly in terms of
      hospital length of stay (LOS), stroke and post-operative infection. METHODS: We
      analyzed hospital LOS, incidence of stroke, infection, and mortality along with
      several clinical variables in 209 patients (38% underwent OPCABG) at a single,
      non academic community hospital. We constructed a series of forward, stepwise,
      multiple-variable regression models using mediastinal infection, hospital LOS,
      and stroke as dependant variables. RESULTS: OPCABG was associated with a shorter
      median hospital LOS (3 days vs. 4 days; p=0.0001) and a reduced occurrence of
      stroke (0% vs. 7.6%; p=0.03). However, mediastinal infections occurred more
      commonly in OPCABG cases (10% vs. 2.2%; p=0.02). CABG and pre-existing renal
      disease were predictors of increased hospital LOS (p< 0.0001) whereas CABG was
      the only factor associated with decreased risk of mediastinal infection (OR=0.21
      (0.05-0.80); p=0.02). CONCLUSIONS: At the community level, OPCABG appears to be
      superior in terms of LOS and incidence of stroke. Paradoxically, CABG surgery
      demonstrates a reduced rate of mediastinal infection.

PMID- 17520573
TI  - The MiniACcor: constructive redesign of an implantable total artificial heart,
      initial laboratory testing and further steps.
AB  - The Aachen Total Artificial Heart (ACcor) has been under development at the
      Helmholtz Institute in Aachen over the last decade. It may serve as a bridge to
      transplant or as a long-term replacement of the natural heart. Based upon
      previous in vivo experiments with the ACcor total artificial heart, it was
      decided to optimize and redesign the pump unit. Smaller dimensions, passive
      filling and separability into three components were the three main design goals.
      The new design is called the MiniACcor, which is about 20% smaller than its
      predecessor, and weighs only 470 grams. Also its external driver/control unit was
      miniaturized and a new microcontroller was selected. To validate the design, it
      was extensively tested in laboratory mock loops. The MiniACcor was able to pump
      between 4.5 and 7 l/min at different pump rates against normal physiological
      pressures. Several requirements for the future compliance chamber and
      transcutaneous energy transmission (TET) system were also measured in the same
      mock loop. Further optimization and validation are being performed in cooperation
      with the Heart and Diabetes Centre North Rhine-Westphalia.

PMID- 17520574
TI  - In vitro and in vivo behaviour of biodegradable and injectable PLA/PGA copolymers
      related to different matrices.
AB  - This study comparatively investigates the in vitro and in vivo behavior of
      injectable polymeric materials for the treatment of bone defects. The tested
      materials were three injectable and biodegradable PLA/PGA 50/50 copolymers
      dispersed in different matrices: Fisograft-gel (GEL) was dispersed in an aqueous
      matrix of poly-ethyl-glycole (PEG); Slurry2 (SL2) was dispersed in an aqueous
      matrix of PEG and dextran; and Slurry6 (SL6) was dispersed in a 3% agarose
      matrix. The biological characterization of these materials was studied by in
      vitro and in vivo tests: the in vitro test assessed the cellular response in
      terms of viability, differentiation and synthetic activity, while the in vivo
      test evaluated the healing capacity of bone defects treated with these
      biomaterials. GEL and SL2 induced a similar response for viability and
      differentiation of MG63 osteoblast-like cells after a 7-day culture, while SL6
      caused a higher production of both interleukin-6 and type I collagen. Since the
      results showed that the materials were biocompatible and not cytotoxic in vitro,
      the in vivo study was carried out: materials were implanted, under general
      anesthesia, in critical size defects of rabbit femoral condyles; after 4 and 12
      weeks, the healing rates and the quality of the regenerated bone were
      histomorphometrically calculated. The SL2-treated defects healed better at 12
      weeks with a more similar microarchitecture of the newly formed bone to normal
      bone in comparison with other materials, as demonstrated by bone volume fraction
      and trabecular thickness values.

PMID- 17520575
TI  - Experimental validation of numerical simulations: a comparison of computational
      fluid dynamics and the oil film method.
AB  - BACKGROUND: Today Computational Fluid Dynamics (CFD) is used for simulating flow
      in many applications. The quality of the results, however, depends on various
      factors, like grid quality, boundary conditions and the computational model of
      the fluid. For this reason, it is important to validate the performed computation
      with experimental results. In this work, a comparison of numerical simulation
      with the oil film method was performed for two cardiovascular applications.
      METHODS: The investigations were conducted at various geometries, such as a
      bended cannula tubing, an impeller of a magnetically levitated rotary blood pump
      and tips of inflow cannulas. The oil film for the experimental validation was
      composed of black oil color and varnish. In the numerical simulation, color
      abrasion was displayed with a special post-processing tool by means of wall
      attached pathlines. RESULTS: With the proper choice of numerical parameters, the
      computer simulations and the oil film method demonstrated good correlation.
      Improper generation of the simulation grid did lead to divergent results between
      the numerical simulation and the experiment. For the pump impeller as well as for
      the inflow cannulas, the calculation and the experiment showed similar flow
      patterns with backflow and stall zones. CONCLUSION: The oil film method
      represents a fast and simple approach to help validate numerical simulations of
      fluid flow. The experimentally generated near wall flow patterns can be easily
      compared with the solution of the CFD analysis.

PMID- 17520577
TI  - Surrogate predictive biomarkers for response to anti-EGFR agents: state of the
      art and challenges.
AB  - The epidermal growth factor receptor (EGFR) plays a key role in cancer
      development and progression in several human malignancies including non-small
      cell lung cancer (NSCLC). Several strategies aimed at inhibiting the EGFR have
      been investigated in the last years, including the use of small tyrosine kinase
      inhibitors (TKIs) directed against the intracellular domain of the receptor and
      monoclonal antibodies targeting its extracellular portion. Subgroups of patients
      who are more likely to respond to TKIs have been identified based on both
      clinical and biological features. Never-smoking history has emerged as the most
      relevant clinical characteristic predictive of response to TKIs in NSCLC, while
      presence of drug-sensitive EGFR mutations and EGFR gene gain represent critical
      biological variables associated with an improved outcome for patients exposed to
      these agents. Recent studies have highlighted the existence of biological factors
      involved in intrinsic and acquired resistance to TKIs, including k-ras, HER-2 and
      EGFR exon 20 mutations. Increasing knowledge of EGFR biology and drug-receptor
      interactions will allow to identify individuals who are likely to derive a
      clinical benefit from the proposed targeted therapy, sparing refractory patients
      expensive and potentially toxic treatment.

PMID- 17520578
TI  - Pharmacology of epidermal growth factor inhibitors.
AB  - Research into the molecular bases of malignant diseases has yielded the
      development of many novel agents with potential antitumor activity. Evidence for
      a causative role for the epidermal growth factor receptor (EGFR), which is now
      regarded as an excellent target for cancer chemotherapy in human cancer, leads to
      the development of EGFR inhibitors. Two classes of anti-EGFR agents are currently
      in clinical use: monoclonal antibodies directed at the extracellular domain of
      the receptor, and the low-molecular-weight receptor tyrosine kinase inhibitors
      acting intracellularly by competing with adenosine triphosphate for binding to
      the tyrosine kinase portion of the EGFR. The effect on the receptor interferes
      with key biological functions including cell cycle arrest, potentiation of
      apoptosis, inhibition of angiogenesis and cell invasion and metastasis.
      Cetuximab, a monoclonal antibody, and the receptor tyrosine kinase inhibitors
      gefitinib and erlotinib are currently approved for the treatment of patients with
      cancer. New agents with clinical activity are entering the clinic, and new
      combinatorial approaches are being explored with the aim of improving the potency
      and pharmacokinetics of EGFR inhibition, to increase the synergistic activity in
      combination with chemotherapy and overcome resistance to the EGFR inhibitors.

PMID- 17520579
TI  - The biology of epidermal growth factor receptor and its value as a
      prognostic/predictive factor.
AB  - Receptor tyrosine kinases play a major role in human carcinogenesis.
      Overexpression of the epidermal growth factor receptor (EGFR) has been associated
      with poor clinical outcome in several types of cancer. In principle, as with
      HER2, the EGFR status of a tumor should predict the likelihood of response to
      EGFR-targeted therapy. However, clinical data have failed to demonstrate a
      relationship between EGFR expression and response to the EGFR-targeted compounds
      cetuximab, gefitinib and erlotinib. Recently, patients reported to be EGFR
      negative have been shown to respond to cetuximab. Possible explanations include
      methodological failures or most likely heterogeneity and complexity of the
      mechanisms of EGFR-mediated molecular carcinogenesis. Immunohistochemistry is the
      most widely used method for measuring EGFR expression; however, its value is
      limited by lack of methodological standardization. Other approaches to measuring
      EGFR such as amplification assays are currently being introduced but need further
      testing before they can enter clinical practice. Mutational analysis seems also
      fruitful in predicting response to anti-EGFR small molecules. Further work is
      needed to identify how EGFR contributes to the carcinogenic and metastatic
      processes.

PMID- 17520580
TI  - Development and clinical indications of cetuximab.
AB  - Cetuximab is a chimeric immunoglobulin G1 monoclonal antibody that targets the
      extracellular domain of the epidermal growth factor receptor (EGFR) with high
      specificity and affinity. It competitively inhibits endogenous ligand binding and
      thereby inhibits subsequent EGFR activation. The EGFR signaling pathways regulate
      cell differentiation, proliferation, migration, angiogenesis and apoptosis, all
      of which become deregulated in cancer cells. EGFR is an important target for
      cancer therapy and many studies have demonstrated that cetuximab is active in
      several types of cancer, particularly colorectal and head and neck cancer.
      Cetuximab enhances the effects of many standard cytotoxic agents, including
      irinotecan, and in combination with chemotherapy it can elicit antitumor
      responses in tumors that previously failed to respond to that chemotherapy.
      Cetuximab also enhances radiation-induced apoptosis. On the basis of a pivotal
      European randomized study (the BOND study) and of 2 clinical studies conducted in
      the USA, cetuximab has been approved in combination with irinotecan for patients
      affected by EGFR-expressing metastatic colon cancer after failure with
      irinotecan. There have only been a few small phase II trials on first-line
      treatment in metastatic colorectal cancer, but the results suggest promising
      activity of cetuximab together with irinotecan or oxaliplatin. There is some
      evidence that additive efficacy can be achieved using EGFR inhibitors in
      combination with vascular endothelial growth factor receptor inhibitors such as
      bevacizumab. A correlation between response and the main toxicity (acne-like skin
      reaction) has been observed but is unclear. EGFR status as a specific marker for
      EGFR inhibitors is controversial. At the moment, EGFR expression does not appear
      to be a predictive factor for response to EGFR inhibitors.

PMID- 17520581
TI  - The rationale for the combination of selective EGFR inhibitors with cytotoxic
      drugs and radiotherapy.
AB  - The epidermal growth factor receptor (EGFR) is frequently overexpressed in a wide
      range of human tumors; such overexpression often correlates with poor prognosis
      and worse clinical outcome. It has been demonstrated that the EGFR autocrine
      pathway plays a crucial role in human cancer since it contributes to a number of
      highly relevant processes in tumor development and progression, including cell
      proliferation, regulation of apoptotic cell death, angiogenesis and metastatic
      spread. For these reasons EGFR is one of the most studied and exploited targets
      for molecular cancer therapy. Two classes of anti-EGFR agents have entered
      clinical practice: monoclonal antibodies and small molecules targeting receptor
      tyrosine kinases. The possibility of combining conventional cytotoxic drugs with
      agents that specifically interfere with key pathways controlling cancer cell
      survival, proliferation, invasion and/or metastatic spread has generated wide
      interest. This could be a promising therapeutic approach for several reasons.
      First, the occurrence of cross-resistance is infrequent since the cellular
      targets and mechanisms of action of cytotoxic drugs and EGFR antagonists are
      different. Second, alterations in the expression and/or activity of genes that
      regulate mitogenic signals may either cause perturbation of cell growth or affect
      the sensitivity of cancer cells to conventional chemotherapy and radiotherapy. In
      fact, EGFR inhibitors have shown activity alone and/or in combination with
      conventional antitumor treatments.

PMID- 17520582
TI  - Clinical management of cutaneous toxicity of anti-EGFR agents.
AB  - Cutaneous toxicity is the most evident adverse effect of epidermal growth factor
      receptor (EGFR) inhibitors because of the specific role played by EGFR in skin
      biophysiology. Dermatological adverse reactions, mainly folliculocentric, have
      been widely reported in the literature. However, the mechanism of these reactions
      is not well defined and their management is still a matter of debate. In this
      paper keratinocyte differentiation, activation and pathways regulating gene
      expression are reviewed in order to improve the understanding of adverse skin
      reactions and obtain success in their management. The authors had the opportunity
      to treat skin reactions induced by cetuximab in a cohort of patients affected by
      metastatic colorectal carcinoma. The aims of this clinical approach were to
      control the signs and symptoms of skin toxicity in order to avoid delay in cancer
      therapy and to use nondrug agents for the treatment of drug-induced skin
      reactions.

PMID- 17520583
TI  - Cetuximab in colon cancer.
AB  - In the last decade remarkable progress has been made in the treatment of
      metastatic colorectal cancer due to the introduction of oxaliplatin and
      irinotecan in clinical practice. The addition of biological agents seems to offer
      a chance to further enhance the activity of conventional chemotherapy. Cetuximab,
      a chimeric mouse-human monoclonal antibody targeting the extracellular domain of
      the epidermal growth factor receptor (EGFR), has shown low but detectable
      activity when employed in pretreated patients either as a single agent or in
      combination with irinotecan. Cetuximab in combination with irinotecan has been
      registered in the USA and Europe for the treatment of patients with metastatic
      colorectal cancer expressing the EGFR after failure of prior irinotecan-based
      cytotoxic therapy. The role of cetuximab in first-line therapy is still
      investigational. Some phase II trials assessing cetuximab plus chemotherapy
      demonstrated a high objective response rate and promising results in terms of
      time to progression and overall survival; data from phase III trials are pending.
      Further studies are needed to investigate the efficacy of cetuximab in
      combination with conventional chemotherapy in the adjuvant/neoadjuvant setting
      and to define criteria for a better selection of patients for this type of
      treatment.

PMID- 17520584
TI  - Treatment of advanced head and neck cancer with cetuximab.
AB  - Cetuximab is a monoclonal antibody targeting the transmembrane receptor HER-1
      (epidermal growth factor receptor, EGFR). In theory, inhibition of EGFR may
      influence tumor behavior since the receptor regulates many important tumor cell
      activities including tumor growth, angiogenesis, and inhibition of the apoptotic
      response to chemotherapy and radiotherapy. Available experimental data suggest
      that cetuximab may enhance the activity of chemotherapy and radiotherapy, reverse
      resistance to some anticancer drugs, and has itself anticancer activity. Early
      clinical data support the experimental results. This paper reviews the published
      findings on cetuximab in the treatment of advanced head and neck cancer and
      points out the future objectives of the clinical research on this drug.

PMID- 17520585
TI  - Rationale and clinical results of multi-target treatments in oncology.
AB  - During the last 10 years, the concept of targeted biological therapy for the
      treatment of cancer has emerged. Targeted agents entered clinical practice only
      recently, and the first drugs with demonstrated clinical efficacy were mainly
      inhibitors of the ErbB family of receptors (i.e., EGFR and HER-2), either
      monoclonal antibodies (MAbs) or tyrosine kinase inhibitors (TKIs). After the
      proof of concept for the clinical efficacy and tolerability of these selective
      agents, it was conceived that most tumors will depend on more than one signaling
      pathway for their growth and survival. As a consequence, different strategies
      were pursued to inhibit multiple signaling pathways or multiple steps in the same
      pathway, either by the development of multi-targeted agents or the combination of
      single targeted drugs. The recent FDA and EMEA approval of sorafenib and
      sunitinib, both multi-targeted TKIs, marked the coming of age of this new
      generation of drugs. Now a whole new wave of multi-targeted compounds is moving
      into clinical trials, raising in the minds of investigators important questions
      about the best strategies to pursue in their use and many doubts about their
      differences and the seeming redundancies in the pipelines of pharmaceutical
      companies. This review will deal with the rationale underlying the multi-targeted
      approach and with the available clinical experience with multi-targeted agents,
      especially focusing on molecules with anti- EGFR mechanisms of action.

PMID- 17520586
TI  - The future of anti-EGFR therapy.
AB  - We report here on the state of our knowledge of the target--namely, the epidermal
      growth factor (EGF) and its receptor--and the challenges related to the methods
      of determination of the epidermal growth factor receptor (EGFR) and associated
      molecular pathways. A critical review of the anti-EGFR therapeutic strategies is
      also outlined. The chimeric anti- EGFR monoclonal antibody cetuximab has been
      approved for EGFR-expressing colorectal tumors in patients who progress after
      irinotecan-based chemotherapy in combination with irinotecan and in squamous cell
      head and neck carcinomas for patients with locally advanced disease in
      combination with radiation therapy or after failure of platinum-based
      chemotherapy in recurrent or metastatic disease (FDA). Cetuximab has the
      potential to provide an improvement of clinical outcome also in other indications
      and tumor types, particularly when used as first-line therapy combined with
      standard chemotherapy for metastatic disease or in the adjuvant setting. Possible
      strategies to improve the effectiveness of anti-EGFR agents are suggested and
      include (i) the use of predictive tools capable of making a more rational
      selection of patients; (ii) the development of standardized predictive biomarkers
      as surrogates for early monitoring of drug efficacy; and (iii) adequate study
      design, statistical analysis and proper end points of efficacy to be applied in
      future prospective trials.

PMID- 17520587
TI  - Segregation of inorganic ions at surfaces of polar nonaqueous liquids.
AB  - We present a short review of recent computational and experimental studies on
      surfaces of solutions of inorganic salts in polar nonaqueous solvents. These
      investigations complement our knowledge of aqueous interfaces and show that
      liquids such as formamide, liquid ammonia, and ethylene glycol can also surface
      segregate large polarizable anions like iodide, albeit less efficiently than
      water. For liquids whose surfaces are covered with hydrophobic groups (e.g.
      methanol), the surface-ion effect all but disappears. Based on the present data a
      general picture of inorganic-ion solvation at the solution-vapor interface of
      polar liquids is outlined.

PMID- 17520588
TI  - Probing the evolution of adsorption on nanoporous solids by in situ solid-state
      NMR spectroscopy.

PMID- 17520589
TI  - The promise and perils of wide-bandgap semiconductor nanowires for sensing,
      electronic, and photonic applications.

PMID- 17520590
TI  - Nanopore unstacking of single-stranded DNA helices.

PMID- 17520591
TI  - Recent developments in ghrelin receptor ligands.
AB  - The 28-amino acid peptide ghrelin is a neuroendocrine hormone synthesized
      primarily in the stomach. It stimulates growth hormone secretion and appetite,
      thus promoting food intake and body-weight gain. The pharmacological properties
      of this peptide are mediated by the growth hormone secretagogue receptor type 1a
      (GHS-R1a). Given its wide spectrum of biological activities, it is evident that
      the discovery of ghrelin and its receptor has opened up many perspectives in the
      fields of neuroendocrine and metabolic research and has had an influence on such
      fields of internal medicine as gastroenterology, oncology, and cardiology. It is
      therefore increasingly likely that synthetic, peptidyl, and nonpeptidyl GHS-R1a
      ligands, acting as agonists, partial agonists, antagonists, or inverse agonists,
      could have both clinical and therapeutic potential. This review summarizes the
      various types of GHS-R1a ligands that have been described in the literature and
      discusses the recent progress made in this research area.

PMID- 17520593
TI  - Robotics in neurosurgery: state of the art and future technological challenges.
AB  - The use of robotic technologies to assist surgeons was conceptually described
      almost thirty years ago but has only recently become feasible. In Neurosurgery,
      medical robots have been applied to neurosurgery for over 19 years. Nevertheless
      this field remains unknown to most neurosurgeons. The intrinsic characteristics
      of robots, such as high precision, repeatability and endurance make them ideal
      surgeon's assistants. Unfortunately, limitations in the current available systems
      make its use limited to very few centers in the world. During the last decade,
      important efforts have been made between academic and industry partnerships to
      develop robots suitable for use in the operating room environment. Although some
      applications have been successful in areas of laparoscopic surgery and
      orthopaedics, Neurosurgery has presented a major challenge due to the eloquence
      of the surrounding anatomy. This review focuses on the application of medical
      robotics in neurosurgery. The paper begins with an overview of the development of
      the medical robotics, followed by the current clinical applications in
      neurosurgery and an analysis of current limitations. We discuss robotic
      applications based in our own experience in the field. Next, we discuss the
      technological challenges and research areas to overcome those limitations,
      including some of our current research approaches for future progress in the
      field.

PMID- 17520594
TI  - Human tactile perception as a standard for artificial tactile sensing--a review.
AB  - In this paper, we examine the most important features of human skin tactile
      properties with special emphasis on the characteristics which are vital in the
      design of artificial systems. Contrary to the visual and auditory senses, the
      touch signal is not a well-defined quantity. As a result, the researchers of this
      field are still dealing with the basics of collecting the most relevant data.
      Following this, mimicking the sense of touch by producing artificial tactile skin
      is a challenging process. Although the sense of touch is widely distributed all
      over the human body, the tactile perception in the human hand is of great
      importance in terms of surgical and medical robotics applications. In this study,
      the role of various mechanoreceptors in the human hand, such as, RA, SA I, SA II,
      and PC units are discussed in relation to the stimuli like force, position,
      softness, and surface texture. Taking human hand as a suitable tactile model, the
      necessary engineering features of an artificial tactile sensor, such as, spatial
      and temporal resolutions, force sensitivity, and linearity, are being reviewed.
      In this work, we also report on the current and possible future applications of
      tactile sensors in various surgical procedures.

PMID- 17520595
TI  - The use of haptics in medical applications.
AB  - Explains the need for haptics (feeling of touch) in medical simulation systems.
      Describes a variety of laparoscopic training systems and other surgical
      simulators. Highlights the Reachin Technologies AB Application Programming
      Interface (API) which is a software tool that significantly speeds up the
      development of surgical simulators.

PMID- 17520596
TI  - Review of robotic fixtures for minimally invasive surgery.
AB  - Instrumental robotics aims to provide function-oriented solutions for given
      technical problems. Micro-Electro- Mechanical-Systems (MEMS) technologies provide
      miniaturized instruments, capable of effective duty-cycles at millimeter ranges.
      This review of current developments describes example devices, developed for
      intracorporeal operations; - system architectures, mainly concerned with problem
      solving approaches and synthetic outlines of modified methods and layouts. This
      review is principally concerned with technologies, but the nature of the medical
      surroundings cannot be disregarded. Robotic devices serve surgical staff to help
      them accomplish surgical procedures. Safety and reliability require high
      functional and structural performance, especially for the active, autonomous
      stages of the operation. All these aspects are considered, and an overview is
      presented of characteristic features generally required for the miniaturization
      of instruments used in remote access surgery.

PMID- 17520597
TI  - A hexapod robot external fixator for computer assisted fracture reduction and
      deformity correction.
AB  - Using hexapod robot kinematics, an external fixator adjustable in all six spatial
      degrees of freedom was developed. As usual with a robot system, bone movements
      can be accomplished with high precision. Contrary to conventional external
      fixators any three-dimensional movement is realisable without giving up stability
      or the necessity to change parts of the construction during the treatment. At
      first a manually controlled fixator with appropriate software was developed. Then
      electromotor elements were added, resulting in a "fracture reduction robot" and a
      fixator featuring load measurement capabilities was built. Finally the concept
      was extended into an "intelligent fixator" which will accomplish automatically
      controlled fracture and deformity treatment in the future.

PMID- 17520598
TI  - Robot-assisted surgery: training and re-training surgeons.
AB  - A renaissance in cardiac surgery is occurring. Cardiac operations are being
      performed through smaller incisions with enhanced technological assistance.
      Specifically, minimally invasive mitral valve surgery has become standard for
      many surgeons. At our institution, we have developed a robotic mitral surgery
      program with the da Vinci telemanipulation system, which has recently gained FDA
      approval. Initial results are reported. Despite procedural success,
      implementation of new technology requires restructuring training programs and re
      training senior surgeons. Ultimately, our desire for improved and less traumatic
      patient care will continue to drive this new technology into the future.

PMID- 17520599
TI  - The FeTouch project: an application of haptic technologies to obstetrics and
      gynaecology.
AB  - Ultrasound technologies have been widely used in gynecology and obstetrics.
      Modern ultrasound systems allow the reconstruction of a 3D model of the subject
      being scanned, but even though visual interfaces have reached very high
      standards, the problem of representing a 3D image on a 2D computer screen still
      exists. Moreover no physical interaction is possible with such a model. The
      FeTouch system, developed at Siena University in the last two years, partially
      solves such issues by using stereo visual feedback and haptic devices. While the
      system can be used with any 3D model obtained from ultrasound scans, its current
      prime use is to allow mothers to interact with a model of the fetus they are
      carrying. The system is freely available on the project web page.

PMID- 17520600
TI  - Brachytherapy--an example of a urological minimally invasive robotic procedure.
AB  - A review of the application of urological robots to the prostate is given,
      together with an examination of the conventional brachytherapy procedure for
      insertion of radioactive seeds to treat prostate cancer. The specification and
      design of a robotic system is provided, which can position a series of needles
      and radioactive pellets in accordance with a pre-operative plan. The needles can
      be withdrawn automatically, leaving the seeds in position.A separate motorised
      system is used to position a trans-rectal ultrasound (U/S) probe, which can be
      used to continually monitor the seed placement. The robot program can be updated
      intra-operatively if the U/S image shows this to be necessary. The demonstrator
      system has been demonstrated in-vitro using a variety of gel and animal tissue
      phantoms. The resulting robot performance shows this to be a viable approach.

PMID- 17520601
TI  - Minimal access coronary revascularisation without cardiopulmonary bypass--the
      impact of robotic technology in the current clinical practice.
AB  - Recent advances in interventional cardiology and cardiac surgery have changed the
      traditional therapeutic algorithms by altering indications, timing and patterns
      of referral for subsequent surgical treatment. The traditional longitudinal
      sternomy incision has been the surgical approach of choice for multi-vessel
      coronary revascularisation. Drawbacks of this incision include potential
      postoperative morbidity, which translates to a prolonged postoperative length of
      stay. The combination of minimally invasive direct coronary artery bypass
      (MIDCAB) with percutaneous transluminal coronary angioplasty (PTCA) or stenting
      (a hybrid approach) is an alternative therapeutic method for patients with
      multivessel coronary artery disease. Recent advances in percutaneous
      interventions have attempted to address the problem of re-stenosis, initially
      through the deployment of bare metal intra-coronary stents and, more recently,
      with drug-eluting stents. Developments in coronary revascularisation have focused
      on reducing both surgical invasiveness and trauma. Patients with significant co
      morbid pathologies, the ones undergoing re-interventions, and especially the
      elderly may benefit from such hybrid procedures by avoiding cardiopulmonary
      bypass and midline sternotomy. Minimally invasive techniques have revolutionized
      cardiothoracic surgery by increasing patient satisfaction and by reducing
      surgical trauma, hospital stay and consequently overall costs. There are however
      limitations. Robot assisted surgery endeavours to minimise these technical
      hindrances and so allow better and more accurate surgical practice whilst
      minimising surgical trauma.

PMID- 17520602
TI  - Simulation of real-time deformable soft tissues for computer assisted surgery.
AB  - The simulation of realistic surgical procedures requires specialized optimized
      algorithms for the models of organs and tissues, which should comply both with
      accuracy of results and run-time computation. This paper provides a general
      survey of methods and approaches used for the simulation of soft tissues in
      Computer Assisted Surgery, discussing the technological challenges to achieve
      realistic simulation of deformation.An application example is presented,
      referring to the simulation of a gastroenterology procedure, abdominal
      paracentesis for the treatment of ascites.

PMID- 17520603
TI  - The development and application of wireless capsule endoscopy.
AB  - The introduction of the Video Capsule Endoscope (VCE) by Given Imaging Ltd.
      (Yoqneam, Israel) in 2001, and its subsequent approval by the FDA as a first line
      tool in the detection of abnormalities of the small bowel, is indicative of the
      rapid acceptance of capsule endoscopy by the practicing gastroenterological
      community. An extensive clinical trials program consistently revealed a high
      diagnostic yield of the VCE when compared to other diagnostic modalities of the
      small intestine. The capsule endoscope contains a miniature color video camera,
      illumination sources, lens, transmitter/controller, antenna, and a power source.
      It is small enough to easily swallow (11 x 26 mm), and it is propelled through
      the gastrointestinal (GI) tract by peristalsis. Its development was enabled by a
      series of technological breakthroughs that occurred at the close of the 20th
      century. The VCE is one of the most exciting examples of the recent trend for
      minimally invasive autonomous medical tools in diagnostic, monitoring, and
      therapeutic applications. Expanding applications of the VCE to additional parts
      of the GI tract, adding physiological sensors, and--in the more remote future-
      addition of therapeutic capabilities will likely occur as this new branch of
      endoscopy develops.

PMID- 17520604
TI  - Image-guided reconstruction of the anterior cruciate ligament.
AB  - The replacement of the ruptured Anterior Cruciate Ligament (ACL) of the knee is a
      biomechanically difficult task. The correct placement of the graft, especially
      the isometry of the tibial and femoral insertion points, is critically to the
      success of the procedure. However, during arthroscopy, the planning of the
      insertion points and accurate execution of the plan is difficult. This paper
      reports an X-ray based system for navigation of the ACL graft implant. The system
      integrates arthroscopy and intra-operative X-ray imaging to identify the correct
      insertion points of the graft. Furthermore, it allows testing the isometry of
      these points before drilling of the femoral and tibial tunnel, and guides the
      drilling itself.

PMID- 17520607
TI  - Robotics in cardiac surgery.
AB  - BACKGROUND: The current status of surgical telemanipulators in the field of
      cardiac surgery is best described as a device in search of applications, as its
      role has not been clearly defined. METHODS/RESULTS: Basic robotic technological
      research and development needs to focus on two key areas: (a) developing methods
      for modeling patient and surgical procedures with the ability to employ that
      customized information in the successful completion of a minimally invasive
      operation; and (b) developing novel human machine interactions that can overcome
      the barriers we currently face in performing surgical tasks using
      telemanipulators. CONCLUSION: Significant breakthroughs in these areas will then
      facilitate the construction and employment of enabling robotic systems, each with
      its specific clinical application.

PMID- 17520608
TI  - Image-guided spinal surgery.
AB  - BACKGROUND: The purpose of this review is to present a comprehensive summary of
      commonly used methods of spinal image guidance, including the benefits and
      limitations of this novel technology. METHODS: The relevant medical literature
      was examined, supplemented by the author's laboratory and clinical experience
      with image-guided spinal surgery. RESULTS: Spinal image guidance has undergone
      significant evolution and rapid technological advancement in recent years. Image
      guidance provides three-dimensional visualization of the spine that can be used
      for preoperative planning and intraoperative navigation. There are three commonly
      used methods of spinal image guidance: preoperative CT-based, fluoroscopy-based,
      and 3D fluoroscopy. Each of these methods demonstrates lower rates of spinal
      implant misplacement than non-image-guided techniques. CONCLUSIONS: Image
      guidance provides highly accurate intraoperative navigation and the medical
      literature suggests that this technology increases the safety of a variety of
      routine and complex spinal procedures.

PMID- 17520609
TI  - Cardiac robotics: a review and St. Mary's experience.
AB  - BACKGROUND: The introduction of the laparoscope led to the progress of surgery to
      a new era, where surgeries that were deemed major are now being performed through
      keyhole incisions with comparable outcomes to open surgery. However, with this
      new technique rose several problems like inaccurate depth perception, diminished
      tactile feedback, need for experienced assistance, and reduction in degrees of
      motion of the surgeons hands all of which inspired surgeons and engineers to look
      for mechanical tools to help in reducing these problems. Henceforth; came the
      application of robotics in surgery. METHODS: A PubMed and Medline search was
      performed on cardiac robotic surgery and its applications in mitral valve repair
      and coronary artery surgery. A total of twenty one articles were picked that
      allude to the subject. A history of robotic surgery was outlined followed by
      applications of robotic manipulation in cardiac surgery was narrated. A quick
      overview of this technology in telemedicine was then outlined followed by future
      prospects of this technology in surgery was contemplated. RESULTS: The experience
      of the group from St. Mary's Hospital, London in this field was outlined. During
      the period of 4 years a total of 102 cases of robotic cardiac surgery were
      performed. The mean length of hospital stay was 3.1 days with a standard
      deviation of 1.4 days and the morbidity of the series explained. There was no
      mortality. CONCLUSION: Early studies have shown that minimally invasive cardiac
      surgery is feasible and yields results similar to conventional cardiac surgery,
      yet it is more technically demanding on the surgeon. As advantageous as this new
      modality is, further multicenter studies are needed to prove its efficacy.

PMID- 17520610
TI  - Non-fluoroscopic catheter-based mapping systems in cardiac electrophysiology-
      from approved clinical indications to novel research usage.
AB  - BACKGROUND: During 20 years of development of catheter-based technologies in the
      management of cardiac arrhythmias, electrophysiological mapping/ablation systems
      have evolved from single-plane fluoroscopic mapping to three-dimensional (3-D)
      non-fluoroscopic computer-based mapping systems. METHODS: Based on magnetic
      technology, the electro-anatomic CARTO mapping system can accurately correlate
      local electrograms with recording sites, by which the system can reconstruct 3-D
      maps with colour-coded electrophysiological information superimposed on the
      anatomy. Whereas the CARTO system is primarily designed for studying cardiac
      activation and not repolarisation, the system has been widely used in the
      diagnosis and ablation of cardiac arrhythmias and in the research of basic
      arrhythmic mechanisms. RESULTS: In order to study cardiac repolarisation in vivo,
      an innovative method, the monophasic action potential (MAP) mapping technique,
      which integrates MAP recording with electroanatomical mapping, has recently been
      developed in our centre. Using the MAP technique, global sequence and dispersion
      of atrial/ventricular repolarisation have been evaluated in vivo in both
      experimental and clinical settings. CONCLUSION: The innovative MAP technique
      provides unique research opportunities for in vivo studies of basic
      electrophysiological mechanisms.

PMID- 17520611
TI  - Essential elements to the establishment and design of a successful robotic
      surgery programme.
AB  - INTRODUCTION: The application of robotic assisted technology has created a new
      era in surgery, by addressing some of the limitations of conventional open and
      laparoscopic surgery. To optimize success the incorporation of robotics into a
      surgical program must be performed with a structured approach. We discuss the key
      factors for building a successful robotic surgery program. MATERIALS AND METHODS:
      Prior to implementing a robotics program certain essential elements must be
      examined. One must assess the overall goals of the program, the initial
      applications of the technology and the time line for success. In addition a
      financial analysis of the potential impact of the technology must also be
      performed. Essential personnel should also be identified in order to form a
      cohesive robotic surgery team. These preparatory sets help coordinate the
      establishment of the program and help to prevent unrealistic expectations; while
      generating the best environment for success. RESULTS: Once the purchase of the
      robotic system has been approved a robotic surgery team is created with certain
      essential components. This staff includes: the surgeons, nursing staff, physician
      assistants, resident/fellows, program coordinator, marketing and a financial
      analysis team. This team will work together to achieve the common goals for the
      program. CONCLUSION: Robotic assisted surgery has grown tremendously over the
      last half decade in certain surgical fields such as urology. The success of
      programs has been variable and often related to the infrastructure of the
      program. The key factors appear to be creation of a sound financial plan, early
      identification of applicable specialties and a motivated surgical team.

PMID- 17520612
TI  - Polish cardio-robot 'Robin Heart'. System description and technical evaluation.
AB  - BACKGROUND: This paper presents the mechanical structure and control system of
      the Polish cardio-robot Robin Heart (RIH). METHODS: The Polish project with
      cardiac surgery robots started in 2000. It was supported by the team from the
      Foundation of Cardiac Surgery Development, Zabrze, in cooperation with research
      centers in Lodz and Warsaw. So far three prototypes, RH0, 1 & 2, of the Robin
      Heart robots family have been designed, constructed and tested. In addition many
      diagnostic systems have been constructed to aid with the assessment of robot
      performance. RESULTS: The main focus of this article examines the technical
      evaluation of our prototypes, based on laboratory test results of both the
      mechanical and control aspects of the telemanipulator systems. CONCLUSIONS: The
      presented test results of both mechanical and electrical aspects of Robin Heart
      telemanipulator systems, show significant progress both in a mechanical and
      control viewpoint, along with an improvement in the characterisation of the test
      parameters.

PMID- 17520613
TI  - Computer-assisted 3D ultrasound-guided neurosurgery: technological contributions,
      including multimodal registration and advanced display, demonstrating future
      perspectives.
AB  - BACKGROUND: Navigation systems are now frequently being used for guiding surgical
      procedures. Existing neuronavigation systems suffer from the lack of updated
      images when tissue changes during surgery as well as from user-friendly displays
      of all essential images for accurate and safe surgery guidance. METHODS: We have
      developed various new technologies for improved neuronavigation. Using
      intraoperative 3D ultrasound (US) imaging, we have developed various registration
      algorithms for using and updating a complete multimodal and multivolume 3D map
      for navigation. RESULTS: We experienced that advanced multimodal visualization
      makes it easy to interpret information from several image volumes and modalities
      simultaneously. Using high quality intraoperative 3D ultrasound, essential
      preoperative information could be corrected due to brain shift. fMRI and other
      important preoperative data could then be used together with intraoperative
      ultrasound imaging for more accurate, safer and improved guidance of therapy.
      CONCLUSIONS: We claim that new features, as demonstrated in the present paper,
      using intraoperative 3D ultrasound in combination with advanced registration and
      display algorithms will represent important contributions towards more accurate,
      safer and more optimized future patient treatment.

PMID- 17520614
TI  - Image-based guidance for minimally invasive surgical atrial fibrillation
      ablation.
AB  - PURPOSE: Atrial fibrillation (AF) is the most common arrhythmia and results in an
      increased risk of ischaemic stroke. Recently, a European consortium has developed
      a new ablation device for minimally invasive surgical AF treatment. The device is
      controlled by a medical robot. Due to the minimal invasive usage, surgery using
      the new device needs appropriate navigation support. In this paper, we describe
      an image-based navigation application to guide the new device intraoperatively.
      METHODS: The navigation procedure is based on intraoperative ultrasound.
      Variations in the position of the ablation device are transferred from the
      software controlling the robot to the navigation system. Due to the flexibility
      of the ablation device, a deformation model predicts the behaviour during
      repositioning. Ablation lines are interactively planned. Actually burned ablation
      lines are visualized during surgery. Several in vitro and ex vivo experimental
      set-ups were built up to test the feasibility. RESULTS: The navigation workflow
      was implemented into navigation software using well-known open-source software
      toolkits. The navigation system has been integrated and tested successfully
      within the overall system. The ablation device could be localized on in vitro and
      ex vivo ultrasound images. CONCLUSION: The performed trials proved the
      applicability of the navigation procedure. More in vivo tests are currently being
      performed to make the new device and the described navigation procedure ready for
      clinical use.

PMID- 17520615
TI  - Short-term impact of a robot-assisted laparoscopic prostatectomy 'mini-residency'
      experience on postgraduate urologists' practice patterns.
AB  - INTRODUCTION: To assist practising urologists acquire and incorporate robot
      assisted laparoscopic prostatectomy (RALP) into their practice, a 5 day mini
      residency (M-R) programme with a mentor, preceptor and potential proctor
      experience was established at the University of California, Irvine, Yamanouchi
      Center for Urological Education. The follow-up results from the initial 21 RALP M
      R participants are presented. METHODS: Between September 2003 and September 2004,
      21 urologists from six states and four countries underwent a RALP M-R. Each
      participant underwent 1:2 teacher:attendee instruction over a 5 day period, which
      included inanimate model skills training, animal/cadaver laboratory skills
      training and operating room observation experience. Participants were also
      offered a proctoring experience at their hospital if they so desired. A
      questionnaire survey was mailed 1-14 months (mean 7.2 months) following
      completion of the mini-residency and these results were tabulated and reviewed.
      RESULTS: A 100% response rate was achieved from the mailed questionnaires. The
      mean M-R participant age was 43 years (range 33-55 years). One-third of the M-R
      participants were practising in an academic environment. Most of the participants
      (55%) had no fellowship training. Of those with fellowship training (45%), three
      (15%) were in laparoscopy and three (15%) were in oncology; 25% of the
      participants were in large (>6 physicians), 25% in small (2-6 physicians) and 15%
      in solo practices; 70% of the participants were located in an urban setting. The
      majority of the participants (80%) had laparoscopic experience during residency
      training and had performed 20-60 laparoscopic cases prior to attending the M-R
      programme. Within 7.2 months after M-R (range 1-14 months), 95% of the
      participants were practising robot-assisted laparoscopic prostatectomy and 25% of
      the RALP M-R participants had also performed robotic-assisted laparoscopic
      pyeloplasty. Of the M-R participants, 38% availed themselves of the
      preceptor/proctor component of the programme; among these, 100% reported that
      they were performing RALP vs. only 92% of the MR participants who did not have a
      proctor experience. The 5 day length of the M-R was considered to be of
      satisfactory duration by 90% of the participants, while 1 participant considered
      it too brief and 1 considered it too long. All but one of the participants rated
      the M-R as a very or extremely valuable experience. All the M-R participants
      indicated that they would recommend this training programme to a colleague.
      CONCLUSIONS: A 5 day intensive RALP M-R course seems to encourage postgraduate
      urologists, already familiar with laparoscopy, to successfully incorporate
      robotic surgery into their practice. The take rate, or the percentage of
      participants performing robotic-assisted surgery within 14 months after M-R, was
      95%. Continued follow-up will ultimately determine the long-term effectiveness of
      this 1 week intensive training programme for postgraduate urologists.

PMID- 17520616
TI  - Integrated image- and function-guided surgery in eloquent cortex: a technique
      report.
AB  - The ability to effectively identify eloquent cortex in close proximity to brain
      tumours is a critical component of surgical planning prior to resection. The use
      of electrocortical stimulation testing (ECS) during awake neurosurgical
      procedures remains the gold standard for mapping functional areas, yet the
      preoperative use of non-invasive brain imaging techniques such as fMRI are
      gaining popularity as supplemental surgical planning tools. In addition, the
      intraoperative three-dimensional display of fMRI findings co-registered to
      structural imaging data maximizes the utility of the preoperative mapping for the
      surgeon. Advances in these techniques have the potential to limit the size and
      duration of craniotomies as well as the strain placed on the patient, but more
      research accurately demonstrating their efficacy is required. In this paper, we
      demonstrate the integration of preoperative fMRI within a neuronavigation system
      to aid in surgical planning, as well as the integration of these fMRI data with
      intraoperative ECS mapping results into a three-dimensional dataset for the
      purpose of cross-validation.

PMID- 17520617
TI  - A novel method in measuring the stiffness of sensed objects with applications for
      biomedical robotic systems.
AB  - BACKGROUND: In this research paper, a new method for determining the compliance
      of various objects with different mechanical properties is presented. The
      structure of the proposed tactile sensor assembly is discussed in detail and the
      performance of the sensor tested experimentally. METHODS: In order to measure the
      stiffness of various sensed objects, the sensor consists of two separate parts.
      The first part is a rigid cylindrical section while the other part is a
      deformable foam-like section. As a practical application, the designed sensor is
      integrated with a typical endoscopic grasper used in minimally invasive
      surgeries. Two theoretical approaches are employed in our analysis. In the first
      approach, which is limited to flat surface objects, the stiffness of the object
      is obtained using a closed-form formula. In the second approach, which can be
      applied to objects with complex irregular shapes, the same parameter is computed
      using finite element analysis. To evaluate the performance of the designed
      grasper tool, eight sensors were placed on top and bottom jaws of the tool and
      objects with known modulus of elasticity were placed between the jaws. RESULTS:
      Keeping the magnitude of the applied forces in the range of 0.1-1 N, we managed
      to measure the stiffness of the sensed objects with reasonable accuracy (an error
      of about 20%). Comparing the experimental data with the analytical and the
      numerical approaches proves that there is a good correspondence between the two
      methods. CONCLUSIONS: The designed prototype can be used in various biomedical
      robotic procedures when performing minimally invasive surgeries. For the first
      time, we managed to make an endoscopic prototype suitable for measuring
      stiffness.

PMID- 17520618
TI  - A novel end-effector design for robotics in image-guided needle procedures.
AB  - BACKGROUND: Robotic end-effectors are being developed to facilitate image-guided
      minimally invasive needle-based procedures, such as tumour ablation, biopsy,
      thoracentesis and blood sampling. METHODS: A novel mechanical end-effector was
      designed to address the challenges associated with any major needle-based
      procedure, focusing on liver biopsy and ablation. In this end-effector
      embodiment, the distal end of a single articulating arm can grip needles and
      instruments and allows a fairly high number of degrees of freedom of movement
      during the complex motions associated with positioning and driving needles, as
      well as the periodic motions associated with breathing patterns. Tightening a
      cable that runs through the articulations fixes the arm in a rigid state,
      allowing insertion of the gripped needle. RESULTS: A design is presented that
      will require electro-mechanical stimulation and remote joystick control. The
      associated forces of cranial-caudal motion of soft tissue organs affects design
      constraints. A simulation study defined the process with tissue phantoms with
      mechanical properties in the range of hepatic tissue and the overlying abdominal
      wall. The robotic arm coupled with our end-effector could be deployed in an image
      guided interventional suite. CONCLUSIONS: Such a switch-able and flexible mode
      for a robotic arm could overcome much of the current limitations for automated
      needle placements for mobile targets, and could mitigate risks from breathing or
      patient motion with a rigid needle gripper in place.

PMID- 17520619
TI  - 1st International Congress of the Minimally Invasive Robotic Association (MIRA),
      7-10 December 2006, Innsbruck, Austria. Congress summary: MIRA and the future of
      surgical robotics (www.teleroboticsurgeons.com).

PMID- 17520620
TI  - Neurosurgical robotics.

PMID- 17520621
TI  - Use of the NeuroMate stereotactic robot in a frameless mode for functional
      neurosurgery.
AB  - BACKGROUND: The aim of this paper is to describe the use of the NeuroMate
      stereotactic robot for functional neurosurgery with a novel frameless ultrasound
      registration system. METHODS: A retrospective review of the evaluation and
      clinical use of the NeuroMate stereotactic robot in a frameless mode for
      functional neurosurgery. RESULTS: Prior to its clinical use a phantom study was
      undertaken to demonstrate an application accuracy of 1.29 mm. Subsequently the
      robot has been used in 153 functional neurosurgical procedures including 113 deep
      brain stimulator implantations. CONCLUSIONS: The NeuroMate stereotactic robot in
      a frameless mode has sufficient accuracy for a range of functional neurosurgical
      procedures, including movement disorder surgery.

PMID- 17520622
TI  - Miniature robotic guidance for pedicle screw placement in posterior spinal
      fusion: early clinical experience with the SpineAssist.
AB  - BACKGROUND: Spinal fusion is a commonly performed procedure for a variety of
      conditions. Pedicle screw fixation has become the standard of care for
      stabilization of the thoracic and lumbar spine. Precise screw placement is
      essential to avoid injury to adjacent neural structures. Patients with severe
      deformity or prior surgery present a challenge to the accurate placement of
      pedicle screws. Additionally, minimally invasive and percutaneous surgical
      techniques also present a greater challenge to accurate screw placement and
      require heavier reliance on intraoperative fluoroscopic imaging, which presents
      an occupational hazard for the surgeon and the operating-room (OR) staff. The
      purpose of this paper is to introduce the SpineAssist, a miniature robotic
      guidance system, developed to assist spine surgeons in the accurate placement of
      pedicle screws. METHODS: The operative technique is described, as is the
      experience and results with 14 patients during a 6 month period during which this
      system was used. RESULTS: The SpineAssist performed successfully in 93% of the
      cases in which it was used. 96% of the screws placed were determined to be within
      1 mm of their planned trajectory. CONCLUSIONS: Difficulties encountered with use
      of the SpineAssist, while minimal, will be described and suggestions made for
      future improvements.

PMID- 17520623
TI  - CASMIL: a comprehensive software/toolkit for image-guided neurosurgeries.
AB  - BACKGROUND: CASMIL aims to develop a cost-effective and efficient approach to
      monitor and predict deformation during surgery, allowing accurate, and real-time
      intra-operative information to be provided reliably to the surgeon. METHOD:
      CASMIL is a comprehensive Image-guided Neurosurgery System with extensive novel
      features. It is an integration of various modules including rigid and non-rigid
      body co-registration (image-image, image-atlas, and image-patient), automated 3D
      segmentation, brain shift predictor, knowledge based query tools, intelligent
      planning, and augmented reality. One of the vital and unique modules is the
      Intelligent Planning module, which displays the best surgical corridor on the
      computer screen based on tumor location, captured surgeon knowledge, and
      predicted brain shift using patient specific Finite Element Model. Also, it has
      multi-level parallel computing to provide near real-time interaction with iMRI
      (Intra-operative MRI). In addition, it has been securely web-enabled and
      optimized for remote web and PDA access. RESULTS: A version of this system is
      being used and tested using real patient data and is expected to be in use in the
      operating room at the Detroit Medical Center in the first half of 2006.
      CONCLUSION: CASMIL is currently under development and is targeted for minimally
      invasive surgeries. With minimal changes to the design, it can be easily extended
      and made available for other surgical procedures.

PMID- 17520624
TI  - The analysis of intraoperative neurosurgical instrument movement using a
      navigation log-file.
AB  - BACKGROUND: The purpose of this study was to define the technical requirements of
      future (tele)robotic neurosurgical systems. We aimed to analyse the movements of
      surgical instruments during neurosurgical procedures. METHODS: A commercially
      available neuronavigation system (StealthStation TREON(plus), Medtronic, USA) was
      used to determine the position and orientation of the surgical instrument. A
      custom-made log-mode was implemented in the software to file instrument
      coordinates intraoperatively. Data was collected during the debulking of
      malignant primary brain tumours, temporal epilepsy surgery and skull base tumour
      surgery. RESULTS: Maximum tip displacement velocity varied, per procedure, in the
      range 6.6-12.7 cm/s and maximum rotational speed 21-40 degrees/s. Maximum
      instrument orientation differences within the volume of movement varied. The
      largest differences were detected during temporal epilepsy surgery (73 degrees
      and 52 degrees in the coronal and axial planes, respectively), while the smallest
      differences were detected in the debulking of an intraventricular tumour.
      CONCLUSIONS: In this study, we have demonstrated the feasibility of motion
      analysis in image-guided neurosurgery. To mimic ordinary open neurosurgery,
      future neurosurgical (tele)robotic systems should at least support translational
      speeds up to 12.7 cm/s, rotational speeds up to 40 degrees/s and differences in
      instrument orientation of up to 73 degrees.

PMID- 17520625
TI  - Miniature robotic guidance for spine surgery--introduction of a novel system and
      analysis of challenges encountered during the clinical development phase at two
      spine centres.
AB  - BACKGROUND: Instrumented spinal fusion surgery is increasingly performed.
      Breaching of the pedicle occurs in 3-55% of screws; clinically significant screw
      misplacements occur in 0-7% of all transpedicular screw placements. Several
      techniques have reduced this incidence but none gained popularity due to cost as
      well as staff issues. Surgical robots offer distinct added value in accuracy and
      minimal invasiveness. The aim of this study is to introduce the SpineAssist--a
      novel spine surgery miniature robot, to discuss the various reasons that had
      prevented full success with its use, to identify patients related, technical
      related, and surgeon related issues, and to offer ways to avoid them. METHODS:
      The SpineAssist miniature robotic system is presented, including a short
      description of the system, its mode of action and a short summary of the surgical
      procedure.15 patients had undergone lumbar fusion procedures using the robotic
      system as part of clinical trials in two Israeli spine centres. A group of 9
      procedures was identified within this prospective cohort. This group represents a
      wide array of technical challenges and human errors which were encountered during
      the clinical development phase of the SpineAssist. These 9 cases were conducted
      in two different sites by different surgical teams, over a period of 9 months,
      with an average interval of 7 weeks between consecutive cases. The cases were
      analysed for patient, system, surgeon and technical issues causing the
      difficulty. Conclusions were drawn as to how to avoid these hurdles in the
      future. RESULTS: In six cases the system operated smoothly, resulting in accurate
      screws placement according to the pre-operative plan, this was confirmed by a
      post-operative CT scan. Technical and surgical challenges which are associated
      with the system early development stage were encountered during 9 procedures. On
      the technical side, the following phenomena were evident: 1) failure of the
      software to automatically achieve satisfying CT-to-fluoro image registration and
      2) failure of the hospital's peripheral equipment/logistics preventing
      registration. On the clinical side of things, the following issues were
      encountered: 1) failure to avoid excessive pressure on the guiding arm caused by
      surrounding soft tissues, leading to a shift in the entry point and trajectory of
      the tool guide. 2) a surgeon applying too much force on the tool guide at the tip
      of the robotic arm, causing deviation from plan. 3) pre-operative plan out of the
      reach of the robot arm and 4) attachment of the clamp to the spinous process in a
      suboptimal orientation. CONCLUSIONS: It is expected that following a steep
      learning curve in the range of 5-10 cases, recommended to take place within 2-3
      weeks time, the surgical team will gain sufficient experience in operating the
      SpineAssist miniature robotic device in order to achieve excellent surgical
      results. The system may be used for wide range of applications including but not
      limited to pedicle screws, trans-facet and trans-laminar screws, biopsy needles,
      vertebroplasty or kyphoplasty tools and more. The preoperative plan has to be
      logical, intraoperative fluoro images taken with care, gentle surgical technique
      must be kept - maintaining the integrity of the posterior elements, and avoiding
      pressure between the robot arms and the soft tissues. During the clinical
      development phase discussed in this study, both teams used an early version of
      the system. Based on the results of this study several significant software and
      hardware improvements have already been implemented. It is our hope that
      describing and analysing our findings will help in planning and preparing for the
      clinical utilization of the SpineAssist system in future sites and will shorten
      their learning curve. By the time this article is published wider clinical
      experience will have been gathered and we expect to soon follow up with an
      analysis of clinical utilization of this system in a larger study group.

PMID- 17520626
TI  - Image-guided transarticular atlanto-axial screw fixation.
AB  - BACKGROUND: The aim of this paper was to outline the use of frameless stereotaxy
      for the safe insertion of C1/C2 transarticular screws in the clinical setting of
      patients with atlanto-axial instability. METHODS: A retrospective review was
      conducted of cases involving the use of image guidance for the accurate placement
      of transarticular C1/C2 screws. The outcome measures considered were neural
      injury, vascular injury, death, and screw placement on postoperative imaging.
      RESULTS: We evaluated 60 patients for image-guided C1/2 transarticular screw
      fixation. There was a total of 109 screws inserted. There were no intraoperative
      complications. CONCLUSIONS: Frameless stereotaxy can be applied safely in a
      clinical setting for transarticular screw fixation. Image guidance can facilitate
      preoperative planning and help determine an optimal trajectory that avoids the
      vertebral artery.

PMID- 17520627
TI  - Image-guided microneurosurgical management of vascular lesions using navigated
      computed tomography angiography. An advanced IGS technology application.
AB  - BACKGROUND: Image-guided neurosurgery has become a standard practice in the last
      few years, with more than 2000 surgical navigation stations installed worldwide.
      In the same time several reports have also demonstrated the efficacy and accuracy
      of computed tomography angiography (CTA) in assessing cerebral vascular
      pathologies. Therefore, the CTA data have recently been implemented into the
      different navigation systems available on the market, making this new technique
      widely applied. The objective of this paper is to discuss and evaluate the
      clinical usefulness of navigated CTA in planning and performing surgery of
      neurovascular lesions. METHODS: Raw images acquired from an helical CTA are
      automatically post-processed on an independent workstation by using a three
      dimensional (3D) volume-rendering images engine and/or using thresholding and
      drawing tools. RESULTS: The data obtained provide useful information in the
      preoperative stage by reconstructing the vascular tree with regard to lesion
      volume, aneurysm neck, dome projection, perforating vessels and their
      relationship with the lesion and the surrounding anatomy. Furthermore, it can
      help in the identification of an arteriovenous malformation (AVM) nidus and
      recognition of its feeding and draining vessels. CONCLUSION: This fascinating
      technique can give some invaluable advantages on the management of cerebral
      vascular lesions and provides excellent information not always available on
      traditional digital subtraction angiography investigation. It has also proved to
      be very accurate, particularly regarding the correlation between the 3D volume
      rendered CT angiography and the intraoperative findings.

PMID- 17520628
TI  - Robot- and computer-assisted craniotomy: resection planning, implant modelling
      and robot safety.
AB  - BACKGROUND: In cases of cranial tumour, manual resection of the cancerous tissue
      can be very stressful and time-consuming, due to the adhesion of the subjacent
      dura mater. Computer-assisted planning, navigation and robotic craniotomy, with
      optional skull reconstruction using customized implants, are of increasing
      clinical interest in craniofacial and neurosurgery. METHODS: Using preoperative
      computed tomography (CT) images, an automatic segmentation of the tumour is
      performed, followed by resection planning. The skull reconstruction is performed
      using computer-assisted implant modeling and manufacturing. Risk analysis of the
      robot-guided intervention led to the development of a new hexapod robot system.
      RESULTS: Results from registration and robot accuracy on plastic and Anatomical
      skull are shown. The concept of a stand-alone safety system is presented to
      supervise the robot during the intervention. The entire process from preoperative
      CT scan to intraoperative robot assisted removal of tumourous bone is shown in
      laboratory and anatomical trials. CONCLUSION: The laboratory and anatomy studies
      conducted so far provided a substantial basis for further improvement of the
      system's integration in the surgical workflow and the final approval of the
      system for initial clinical studies.

PMID- 17520629
TI  - Robotics in cardiac surgery: the Istanbul experience.
AB  - BACKGROUND: Robots are sensor-based tools capable of performing precise, accurate
      and versatile actions. Initially designed to spare humans from risky tasks,
      robots have progressed into revolutionary tools for surgeons. Tele-operated
      robots, such as the da Vinci (Intuitive Surgical, Mountain View, CA), have
      allowed cardiac procedures to start benefiting from robotics as an enhancement to
      traditional minimally invasive surgery. METHODS: The aim of this text was to
      discuss our experience with the da Vinci system during a 12 month period in which
      61 cardiac patients were operated on. There were 59 coronary bypass patients
      (CABG) and two atrial septal defect (ASD) closures. RESULTS: Two patients (3.3%)
      had to be converted to median sternotomy because of pleural adhesions. There were
      no procedure- or device-related complications. CONCLUSION: Our experience
      suggests that robotics can be integrated into routine cardiac surgical practice.
      Systematic training, team dedication and proper patient selection are important
      factors that determine the success of a robotic surgery programme.

PMID- 17520630
TI  - A new minimally invasive heart surgery instrument for atrial fibrillation
      treatment: first in vitro and animal tests.
AB  - BACKGROUND: The paper presents a new robotic system for beating heart surgery.
      The final goal of this project is to develop a tele-operated system for the
      thoracoscopic treatment of patients with atrial fibrillation. The system consists
      of a robot that moves an innovative end-effector used to perform lines as in the
      Cox-Maze technique. METHODS: The device is an electrode mesh that is introduced
      in the thorax through a trocar and is deployed inside the left atrium, where it
      can create selective ablation lines at any atrial region, using radio frequency.
      The current version of the umbrella has 22 electrodes. Using visual feedback from
      an ultrasound based navigation system, the surgeon can choose which electrodes on
      the mesh to activate. Once the umbrella is in contact with the endocardium of the
      left atrium, at the expected position, the surgeon activates the chosen
      electrodes sequentially. The umbrella can then be moved to another position.
      RESULTS: In vitro and in vivo animal tests have been carried out in order to test
      and improve the instrument, the robotic system and the operative procedure.
      CONCLUSIONS: The performed trials proved the ability of the system to treat
      atrial fibrillation. More in vivo tests are currently being performed to make the
      robot and its device ready for clinical use.

PMID- 17520631
TI  - Influence of anastomotic techniques in totally endoscopic coronary artery bypass.
AB  - BACKGROUND: Beating heart totally endoscopic coronary artery bypass grafting
      (TECAB) utilizing a computer-enhanced telemanipulation system is a technically
      challenging procedure. The objective of our study was to compare two different
      anastomotic techniques. METHODS: Ten canine beating heart TECAB procedures were
      performed using Intuitive's daVinci surgical system. Left internal mammary artery
      (LIMA) to left anterior descending coronary artery (LAD) anastomosis was
      performed on all subjects. Anastomosis varied between a conventional running
      suture (8-0 Gore-tex) (group I) and an interrupted nitinol u-clip anastomosis
      (group II). On-table angiography was then performed to assess graft patency.
      RESULTS: While internal mammary artery (IMA) mobilization time decreased over the
      course of the study (p = 0.017), there was no significant difference in ischaemia
      time, anastomosis time or angiographic assessment between anastomotic techniques.
      Although operative time in group II was significantly shorter than in group I,
      this was likely due to the small sample size. There were no differences in
      anastomotic time or coronary occlusion time. There were also no significant
      differences in canine weight, IMA mobilization time, lipectomy/pericardiotomy,
      LAD identification, subxiphoid port placement, stabilizer position, or LAD
      dissection time between the cases performed with the conventional running suture
      and the cases performed with u-clips. CONCLUSION: Interrupted nitinol clip
      anastomosis or conventional running suture anastomoses are equally favourable in
      the short term when performing a TECAB procedure.

PMID- 17520633
TI  - The role of medical simulation: an overview.
AB  - Robotic surgery and medical simulation have much in common: both use a mechanized
      interface that provides visual "patient" reactions in response to the actions of
      the health care professional (although simulation also includes touch feedback);
      both use monitors to visualize the progression of the procedure; and both use
      computer software applications through which the health care professional
      interacts. Both technologies are experiencing rapid adoption and are viewed as
      modalities that allow physicians to perform increasingly complex minimally
      invasive procedures while enhancing patient safety. A review of the literature
      and industry developments concludes that medical simulators can be useful tools
      in determining a physician's understanding and use of best practices, management
      of patient complications, appropriate use of instruments and tools, and overall
      competence in performing procedures. Future use of these systems depends on their
      impact on patient safety, procedure completion time and cost efficiency. The
      sooner simulation training can be used to support developing technologies and
      procedures, the earlier, and typically the better, the results. Continued studies
      are needed to identify and ensure the ongoing applicability of these systems for
      both training and certification.

PMID- 17520634
TI  - Robotic mitral surgery at East Carolina University: a 6 year experience.
AB  - BACKGROUND: Robotic mitral valve repair using the da Vinci telemanupilation
      system has become the standard of care at many centres worldwide. We perform the
      first robotic MV repair in the United States in the year 2000. This article
      reviews our 6 year experience and current technique of robotic MV repair as well
      as future trends in the field. METHODS: Retrospective review of our initial 200
      robotic MV repairs. Patient demographics, operative times, type of repairs,
      morbidities, mortality, success of the repair including need for reoperations
      were reviewed. RESULTS: The average age was 57 +/- 0.9 years. Average time for
      CPB was 156 minutes and for cross clamp 119 minutes. There was one operative
      death (0.5%) with no device related complications. Postoperative TEE demonstrated
      no MR in 187 (93.5%) patients, trace MR in 6 (3%) patients, moderate MR in 5
      (2.5%) patients, and SAM in 2 (1%) patients. Five (2.5%) patients required
      reoperation for failed repairs. CONCLUSIONS: Robotic MV repair operations are
      safe with excellent early results. Follow-up studies are needed to determine
      repair longevity. We must continue to improve the current technology in order to
      develop the next generation of tools that will facilitate robotic MV repairs.

PMID- 17520635
TI  - Long-distance robotic telesurgery: a feasibility study for care in remote
      environments.
AB  - BACKGROUND: Basic telesurgical manoeuvres were conducted with signal delays.
      METHODS: Eight test subjects conducted four manoeuvres. Time delays of 0-1000 ms
      were investigated. Time to task completion and error rate were recorded in
      sequential delays of 0-600 ms. Additionally, blinded random delays of 0-1000 ms
      were studied. RESULTS: In the sequential trials (0-600 ms), there were no
      significant differences in average task time compared to zero latency. The error
      rate remained low despite increasing time delay, and was significantly less at
      500 ms (p < 0.05). In the random trials, task time was significantly greater at
      delays of 500, 600, 800 and 1000 ms (p < 0.05). There were no significant
      differences in error rates (p = 0.252). CONCLUSIONS: Operators are capable of
      performing surgical exercises at significant delays. Latent video feedback is
      difficult for telesurgery. Visual or virtual reality cues should be implemented
      to aid the operator in a high-cadence telesurgery environment.

PMID- 17520636
TI  - Robotic cardiac surgery.
AB  - BACKGROUND: Cardiac surgery, traditionally conducted via median sternotomy, has
      been recently forwarded by progressively advanced technology facilitating sternal
      sparing minimally invasive, access to the heart. Robotic systems, comprised of
      miniaturized surgical instruments mounted on long thin shafts with multiple
      degrees of range of motion coupled with a dual camera endoscope providing true
      three-dimentional high-magnification visualization have greatly propelled this
      field. METHODS: The robotic system and the literature base pertaining to robotic
      cardiac surgery is reviewed in depth. RESULTS: Robotic cardiac surgical
      procedures have been performed to repair and replace the mitral valve, bypass
      coronary arteries, close atrial septal defects, implant left ventricular pacing
      leads, and resect intracardiac tumors. CONCLUSIONS: As minimally invasive and
      robotic surgical technology advances, so proceeds the spectrum of potential
      applications for robotic cardiac surgery.

PMID- 17520637
TI  - Robotic application in epilepsy surgery.
AB  - BACKGROUND: Epilepsy surgery is cost-effective and dependent on patient
      selection, localization and meticulous technique. We report the use of a new
      robotic system in this surgery for the first time. METHODS: The brain is imaged
      for both image guidance and robotic application. The robot uses CT-visible
      reflective fiducials. Registration is performed by image-guided surgery (IGS)
      system and the robot. The robot is used to insert depth electrodes for intra
      operative epileptic focus localization and to localize the temporal horn.
      RESULTS: This technique was used in three patients; the catheter tip was found in
      the temporal horn in all cases and saved considerable operating time compared to
      previous experience. CONCLUSION: It is therefore feasible to use the robot to
      localize the temporal horn and place depth electrodes during epilepsy surgery
      with greater precision and consistency and potential time savings.

PMID- 17520638
TI  - A surgical telemanipulator for femur shaft fracture reduction.
AB  - BACKGROUND: We present a surgical telemanipulator system supporting long bone
      fracture reduction procedures. This paper gives an overview of the robotic system
      developed by our working group and describes a possible workflow for
      telemanipulated fracture reduction. The concepts enabling an intuitive control of
      the robot using a joystick with force feedback as input device are also
      described. METHODS: With our robotic set-up we performed a test series, in order
      to evaluate the achievable reposition accuracies and operation times. 11 femoral
      shaft fractures in seven human donors have been reduced with the telemanipulator
      and the results have been compared with those achieved by conventional manual and
      navigated manual repositions. RESULTS: All fractures in our test series could be
      reduced successfully with the telemanipulator, achieving a mean rotational
      deviation of 4.9 degrees in axial direction and 2.5 degrees and 3.5 degrees in AP
      and lateral direction. We could find no statistically significant difference
      between the accuracies achieved by the telemanipulator and those achieved by the
      two manual procedures. The image intensifier usage times of our telemanipulated
      repositions were conspicuously lower compared to the conventional manual
      repositions and statistically significant lower compared to the navigated
      repositions. CONCLUSION: We could show that robot-assisted fracture reduction is
      possible, yielding good accuracies and a conspicuous reduction of X-ray
      irradiation. However, we also show the limitations regarding reposition
      accuracies of telemanipulated fracture reduction when it is based on 2D X-ray
      imaging only. From the combination of 3D imaging, automated computation of the
      reduction parameters, and automated force/torque guided reduction by the robot we
      expect to overcome these limitations in our future work.

PMID- 17520639
TI  - Load balance in total knee arthroplasty: an in vitro analysis.
AB  - BACKGROUND: One of the goals of total knee arthroplasty (TKA) is to balance the
      loads between the compartments of the knee. An instrumented load cell that
      measures compartment loads in real time is utilized to evaluate conventional,
      qualitative methods of achieving this balance. METHODS: TKA was performed on 10
      cadaveric knees. Prior to and after load balancing, compartment forces were
      measured at flexion angles of 0-90 degrees. Knees were randomly assigned into one
      of two groups, based upon whether or not the surgeons could visualize the load
      cell's output during balancing. RESULTS: Prior to attempting load balance, there
      were significant differences between the medial and lateral compartment loads for
      all knees (p < 0.05). After attempting balance with the aid of the load cell,
      there was equal load balance at all angles studied. Without the aid of the load
      cell, balance was not consistently achieved at every angle. CONCLUSIONS:
      Conventional load balancing techniques in TKA are not perfect.

PMID- 17520640
TI  - MRI/TRUS data fusion for brachytherapy.
AB  - BACKGROUND: Prostate brachytherapy consists in placing radioactive seeds for
      tumour destruction under transrectal ultrasound imaging (TRUS) control. It
      requires prostate delineation from the images for dose planning. Because
      ultrasound imaging is patient- and operator-dependent, we have proposed to fuse
      MRI data to TRUS data to make image processing more reliable. The technical
      accuracy of this approach has already been evaluated. METHODS: We present work in
      progress concerning the evaluation of the approach from the dosimetry viewpoint.
      The objective is to determine what impact this system may have on the treatment
      of the patient. Dose planning is performed from initial TRUS prostate contours
      and evaluated on contours modified by data fusion. RESULTS: For the eight
      patients included, we demonstrate that TRUS prostate volume is most often
      underestimated and that dose is overestimated in a correlated way. However, dose
      constraints are still verified for those eight patients. CONCLUSIONS: This
      confirms our initial hypothesis.

PMID- 17520641
TI  - The robotic approach for mediastinal lesions.
AB  - BACKGROUND: We report here our institutional experience and reflect the relevant
      literature concerning the robotic approach in diagnostic and therapeutic
      interventions for mediastinal lesions. METHODS: During August 2001-December 2005,
      33 patients (15 males and 18 females aged 18-77 years) with mediastinal masses
      were operated on minimally invasively using the da Vinci robotic system. There
      were 22 thymectomies (nine thymomas), four resections of paravertebral
      neurinomas, one ectopic mediastinal parathyroidectomy, one resection of a
      lymphangioma, one resection of ectopic goitre, one resection of lymph node
      metastasis of thyroid carcinoma and three oesophageal procedures (one leiomyoma,
      one traction diverticulum and one foregut cyst). RESULTS: There were three (9%)
      open conversions due to surgical problems, 30 procedures (91%) were completed
      successfully using the da Vinci robot. There was no surgical mortality, no
      relevant intraoperative blood loss and no major surgical complication in any of
      the patients. As a minor complication (3%), an incomplete and transient palsy of
      the left laryngeal recurrent nerve was observed after resection of a tumour from
      the aortopulmonary window. The median overall operation time was 134 (range 54
      314) min, including 103 (range 39-272) min for the robotic act. CONCLUSIONS:
      Various different mediastinal procedures have been shown to be feasible and safe
      when performed with the robot. As the technical benefits of the da Vinci system
      are most advantageous in tiny and difficult-to-reach anatomical regions, the
      mediastinum should remain an area of special interest for robotic surgeons.
      Randomized trials and follow-up studies have been initiated in order to evaluate
      the clinical impact of the robotic approach.

PMID- 17520642
TI  - Computer-aided navigation for arthroscopic hip surgery using encoder linkages for
      position tracking.
AB  - BACKGROUND: While arthroscopic surgery has many advantages over traditional
      surgery, this minimally invasive technique is not often applied to the hip joint.
      Two main reasons for this are the complexity of navigating within the joint and
      the difficulty of correctly placing portal incisions without damaging critical
      neurovascular structures. This paper proposes a computer-aided navigation system
      to address the challenges of arthroscopic hip surgery. METHODS: Unlike
      conventional arthroscopic methods, our system uses a hyper-redundant encoder
      linkage to track surgical instruments, thus eliminating the occlusion and
      distortion problems associated with standard optical and electromagnetic tracking
      systems. The encoder linkage position information is used to generate a computer
      display of patient anatomy. RESULTS: The tracking error from the encoder linkage
      was evaluated to be within an acceptable range for this tracking prototype, and
      the new computer-aided approach to arthroscopic hip surgery was applied to a
      prototype system for concept verification. CONCLUSION: This navigation system for
      arthroscopic hip surgery can be used as a tool to address the challenges of joint
      navigation and portal placement in arthroscopic hip surgery by visually
      supplementing the limiting view from the arthroscope. The introduction of a
      tracking linkage shows significant potential as an alternative to other tracking
      systems. Positive feedback about the completed demo system was obtained from
      surgeons who perform arthroscopic procedures.

PMID- 17520643
TI  - 3D ultrasound in robotic surgery: performance evaluation with stereo displays.
AB  - BACKGROUND: The recent advent of real-time 3D ultrasound (3DUS) imaging enables a
      variety of new surgical procedures. These procedures are hampered by the
      difficulty of manipulating tissue guided by the distorted, low-resolution 3DUS
      images. To lessen the effects of these limitations, we investigated stereo
      displays and surgical robots for 3DUS-guided procedures. METHODS: By integrating
      real-time stereo rendering of 3DUS with the binocular display of a surgical
      robot, we compared stereo-displayed 3DUS with normally displayed 3DUS. To test
      the efficacy of stereo-displayed 3DUS, eight surgeons and eight non-surgeons
      performed in vitro tasks with the surgical robot. RESULTS: Error rates dropped by
      50% with a stereo display. In addition, subjects completed tasks faster with the
      stereo-displayed 3DUS as compared to normal-displayed 3DUS. A 28% decrease in
      task time was seen across all subjects. CONCLUSIONS: The results highlight the
      importance of using a stereo display. By reducing errors and increasing speed, it
      is an important enhancement to 3DUS-guided robotics procedures.

PMID- 17520645
TI  - Robotic foregut surgery.
AB  - BACKGROUND: Computer-assisted surgical systems, or surgical robots as they are
      more commonly called, are complex new devices which may be used to perform
      minimally invasive surgical procedures. There are certain technical limitations
      to a traditional laparoscopic approach that these devices can help a surgeon to
      overcome. Several surgical teams have applied these new devices to surgical
      procedures of the upper gastrointestinal tract and foregut. METHODS: A
      retrospective review of the currently published literature on robotic foregut
      surgery. RESULTS: Robotic foregut surgery appears to be feasible and safe. These
      procedures may be associated with increased operative time and cost when compared
      to their traditional laparoscopic counterparts. Procedures that require complex
      manoeuvres, delicate dissection, or a magnified high-definition image may be best
      suited to a computer-assisted approach. CONCLUSIONS: Robotic foregut surgery is
      an exciting new field with tremendous potential for growth and dissemination.

PMID- 17520646
TI  - The legal and economic forces that will shape the international market for
      cybersurgery.
AB  - BACKGROUND: Despite the common use of medical devices most health care providers
      have little understanding how a device alters medical malpractice litigation.
      Such knowledge will be increasingly valuable as cybersurgery (i.e. remote robotic
      surgery) becomes routine. METHODS: Review of the laws governing products and
      telecommunication liability. RESULTS: Litigation after cybersurgery 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 telecommunication company. Robotics manufacturers can
      obtain virtual immunity from liability if they elected to place their devices on
      the market after obtaining [see text]360 per-market approval from the FDA.
      However, because [see text]360 pre-market approval is expensive and time
      consuming most medical devices on the market (including the robotic surgical
      instruments) do not have immunity to products liability. Consequently, after an
      adverse cybersurgical outcome a manufacturer of a robotic surgical instrument
      faces liability for failure to warn, design defects, and failure to properly
      manufacture. As for telecommunication providers, existing law provides them with
      immunity from liability. CONCLUSIONS: Litigation following cybersurgery will
      involve multiple defendants who are likely to use "finger pointing" defenses.
      Accordingly, there will be liability traps associated with providing
      cybersurgery.

PMID- 17520647
TI  - Robotic laparoscopic distal gastrectomy: a comparison of the da Vinci and Zeus
      systems.
AB  - BACKGROUND: The robotic surgical systems working on a master-slave principle have
      been developed and used in the worldwide in cardiac, urologic, and general
      surgery. METHODS: The two robotic systems, the da Vinci and the Zeus Robotic
      Surgical System (Intuitive Surgical, Calif., USA), were compared with the aim of
      evaluating operative feasibility and technical efficacy in distal gastrectomy.
      RESULTS: During laparoscopic gastrectomy, the da Vinci System (n = 2) had a
      shorter total operative time (445 versus 656 minutes; p = 0.09) and less blood
      loss (65 versus 277 mL; p = 0.08) compared with the Zeus System (n = 3). The
      articulated instruments of both systems were useful in lymph node dissection,
      isolation of vessels in fat tissue, ligation of vessels, and intraabdominal
      anastomosis of the gastrointestinal tract. Robotic laparoscopic procedures can be
      performed effectively using either the da Vinci or Zeus System. CONCLUSION: In
      this limited study, the robotic instruments, especially those of da Vinci system,
      made it easier to complete tissue dissection including lymph nodes, complicated
      endoscopic anastomoses, and ligatures in a closed cavity.

PMID- 17520648
TI  - Surgical techniques: robot-assisted laparoscopic hysterectomy with the da Vinci
      surgical system.
AB  - BACKGROUND: Advanced gynecologic pathology and the surgical limitations of
      conventional laparoscopy have often been cited as impediments to converting
      hysterectomy from a procedure predominantly performed by laparotomy to one
      accomplished by laparoscopy. Recently, the use of robotic technology as a means
      to facilitate the laparoscopic completion of a hysterectomy was introduced.
      METHODS: Application of robotic-assistance with the da Vinci surgical system to
      complete a laparoscopic hysterectomy. RESULTS: Advantages to this approach have
      been the improved dexterity and precision of the instruments coupled with three
      dimensional imaging. Published preliminary data have shown feasibility and safety
      to this approach. CONCLUSION: The following paper demonstrates a safe and
      efficient surgical technique for completing a robot-assisted laparoscopic
      hysterectomy with the da Vinci Surgical System.

PMID- 17520649
TI  - A novel laparoscopic mesh placement part task trainer.
AB  - BACKGROUND: We present a surgical simulator, developed for the training of a
      laparoscopic surgery and in particular for mesh placement during an inguinal
      herniorrhaphy. METHODS: Major technical issues related to virtual surgery
      training systems include virtual patient modelling, collision detection and
      collision response, haptic and graphic rendering, 3-D motion tracking and some
      special effects, such as bleeding, cauterizing and so on. Among these problems,
      real-time deformation modelling and collision detection are the most challenging
      research topics. RESULTS: In this paper, we describe novel approaches addressing
      the above issues, which have been successfully adopted in our bimanual hernia
      repair simulator. CONCLUSION: The implementations of our new collision detection
      and deformation appear to work well, even at haptic rates for the limited scope
      of mesh placement training. More sophisticated techniques are needed for full
      organ deformation especially for blunt dissection simulation.

PMID- 17520650
TI  - Robotic prostatectomy: the first UK experience.
AB  - BACKGROUND: We describe a teamwork approach to setting up the UK's first clinical
      programme for robotically assisted laparoscopic radical prostatectomy. METHODS:
      On 22 November 2004 the Imperial Robotic Urological Surgery Group performed their
      first robotically assisted prostatectomy. Robotically assisted prostatectomy
      lends itself to division into eight definable stages. A team of four consultant
      urological surgeons utilized a structured rotating system, using these stages,
      for time at the console and tableside assisting. Fluidity of surgery was
      maintained by a surgeon acting as the tableside assistant for the stage prior to
      moving to the console. Data was collected prospectively for the first 50 cases
      and parameters associated with the learning curve compared to other reported
      series. RESULTS: Median operative time of 369.5 mins, median blood loss of 700
      ml, with 12% of patients requiring a blood transfusion. Four patients required
      conversion to an open procedure; one resulting from equipment failure and three
      due to failure of progression. Four patients had an anastomotic leak with
      resulting ileus and two patients sustained rectal injuries, which were repaired
      intraoperatively using the robot. Median hospital stay was 4 days with a 22%
      positive surgical margin rate. CONCLUSION: Parameters indicative of the learning
      curve are comparable to existing published initial series of other robotic
      centres. The use of teamwork has enabled us to provide safe and time-efficient
      training for four surgeons simultaneously. The structured approach used in this
      setting demonstrates that urological surgeons of varying laparoscopic experience
      can acquire the skills necessary to competently perform laparoscopic radical
      prostatectomy.

PMID- 17520651
TI  - Robots and lasers: the future of cardiac tissue ablation?
AB  - BACKGROUND: The future of medicine is tied-up in robotics and lasers. We've heard
      the hype for years, but only in the last 10 years has it actually started to come
      to fruition that robotic systems are beginning to play a role in surgery.
      METHODS: Multiple groups have reported over the past 10 years on increasingly
      complex cardiac surgical procedures being performed with the aid of robotic
      systems. With an increasing percentage of atrial fibrillation and with insight
      that atrial fibrillation results in poor long-term survival, attempts have been
      made to create a surgical cure. RESULTS: Much work has been done in the past
      several years to develop a less-invasive surgical option than the standard cut
      and-sew Maze to achieve pulmonary vein ablation. Laser is a unique energy source
      for tissue ablation because it is a form of light. CONCLUSION: While traditional
      energy sources focus on applying heat-based elements to the tissue's surface
      allowing temperature to propagate across the thickness of the tissue laser is an
      innovative, tissue-specific energy for creating tissue ablation.

PMID- 17520652
TI  - Detection of tumours using a computational tactile sensing approach.
AB  - BACKGROUND: A new method is presented for determining the existence of an
      embedded object in biological tissue. METHODS: We propose a method for modelling
      tissue containing a simulated tumour. Indications of the existence of a tumour
      that appear on the surface of the tissue were also determined. FEM provided
      properties such as the shape, size, depth and location of tumour. RESULTS: A
      number of different cases were created and solved by the software and tactile
      images and stress graphs were extracted. These results clearly showed the
      existence of the tumour in the tissue. Maximum stresses were used to create
      tactile maps. Simulation results demonstrated good agreements with other studies.
      CONCLUSIONS: Three-dimensional analysis leads to a novel method of predicting the
      characteristics of a tumour and can be directly applied to the incorporation of
      tactile sensing in artificial palpation, helping surgeons in non-invasive
      procedures.

PMID- 17520653
TI  - Mechatronic design of haptic forceps for robotic surgery.
AB  - BACKGROUND: Haptic feedback increases operator performance and comfort during
      telerobotic manipulation. Feedback of grasping pressure is critical in many
      microsurgical tasks, yet no haptic interface for surgical tools is commercially
      available. METHODS: Literature on the psychophysics of touch was reviewed to
      define the spectrum of human touch perception and the fidelity requirements of an
      ideal haptic interface. Mechanical design and control literature was reviewed to
      translate the psychophysical requirements to engineering specification. High
      fidelity haptic forceps were then developed through an iterative process between
      engineering and surgery. RESULTS: The forceps are a modular device that integrate
      with a haptic hand controller to add force feedback for tool actuation in
      telerobotic or virtual surgery. Their overall length is 153 mm and their mass is
      125 g. A contact-free voice coil actuator generates force feedback at frequencies
      up to 800 Hz. Maximum force output is 6 N (2N continuous) and the force
      resolution is 4 mN. The forceps employ a contact-free magnetic position sensor as
      well as micro-machined accelerometers to measure opening/closing acceleration.
      Position resolution is 0.6 microm with 1.3 microm RMS noise. The forceps can
      simulate stiffness greater than 20N/mm or impedances smaller than 15 g with no
      noticeable haptic artifacts or friction. CONCLUSION: As telerobotic surgery
      evolves, haptics will play an increasingly important role.

PMID- 17520654
TI  - Experiments on robot-assisted navigated drilling and milling of bones for pedicle
      screw placement.
AB  - BACKGROUND: This article presents experimental results for robot-assisted
      navigated drilling and milling for pedicle screw placement. The preliminary study
      was carried out in order to gain first insights into positioning accuracies and
      machining forces during hands-on robotic spine surgery. Additionally, the results
      formed the basis for the development of a new robot for surgery. METHODS: A
      simplified anatomical model is used to derive the accuracy requirements. The
      experimental set-up consists of a navigation system and an impedance-controlled
      light-weight robot holding the surgical instrument. The navigation system is used
      to position the surgical instrument and to compensate for pose errors during
      machining. Holes are drilled in artificial bone and bovine spine. A quantitative
      comparison of the drill-hole diameters was achieved using a computer. RESULTS:
      The interaction forces and pose errors are discussed with respect to the chosen
      machining technology and control parameters. Within the technological boundaries
      of the experimental set-up, it is shown that the accuracy requirements can be met
      and that milling is superior to drilling. CONCLUSIONS: It is expected that robot
      assisted navigated surgery helps to improve the reliability of surgical
      procedures. Further experiments are necessary to take the whole workflow into
      account.

PMID- 17520655
TI  - Supplemental wide field-of-view monitor improves performance in surgical
      telerobotic movement time.
AB  - BACKGROUND: This study investigates the effect of a supplemental wide field-of
      view (FOV) monitor on performance at high magnifications where the benefits of
      robotic surgery have greater importance. METHODS: Ten surgically naive
      participants performed a simple aimed movement task under two different monitor
      conditions. The task is intended to emulate the need to locate an instrument
      outside the surgeon's FOV and return it to a 'home' position without the need to
      zoom. One monitor condition used a narrow FOV (25x) coupled with a supplemental
      wide FOV (3x). The second monitor condition used only a narrow FOV. RESULTS:
      Using a supplemental wide FOV in addition to a narrow FOV improved task
      performance by at least 33%, with greater consistency and reliability.
      CONCLUSION: The supplemental wide FOV monitor provided additional information to
      the participant, allowing more efficient performance at high magnifications
      without the need for zooming.

PMID- 17520659
TI  - Estrogen receptor alpha/beta isoforms, but not betacx, modulate unique patterns
      of gene expression and cell proliferation in Hs578T cells.
AB  - The actions of 17beta-estradiol (E2) and selective estrogen receptor modulators
      (SERMs) have been extensively investigated regarding their ability to act through
      estrogen receptor-alpha (ERalpha) to perturb estrogen receptor positive (ER+)
      breast cancer (BC) growth. However, many BCs also express ERbeta, along with
      multiple estrogen receptor (ER) splice variants such as ERbetacx, an ERbeta
      splice variant incapable of binding ligand. To gain a more comprehensive
      understanding of ER action in BC cells, we stably expressed ERalpha, ERbeta, or
      ERbetacx under doxycycline (Dox) control in Hs578T cells. Microarrays performed
      on E2 or 4OH-tamoxifen (4HT) treated Hs578T ERalpha and ERbeta cells revealed
      distinct ligand and receptor-dependent patterns of gene regulation, while the
      induction of ERbetacx did not alter gene expression patterns. E2 stimulation of
      Hs578T ERbeta cells resulted in a 27% decrease in cellular proliferation,
      however, no significant change in proliferation was observed following the
      exposure of Hs578T ERalpha or ERbeta cells to 4HT. Expression of ERbetacx in
      Hs578T cells did not effect cellular proliferation. Flow cytometry assays
      revealed a 50% decrease in E2-stimulated Hs578T ERbeta cells entering S-phase,
      along with a 17% increase in G0/G1 cell-cycle arrest. We demonstrate here that
      ERalpha and ERbeta regulate unique gene expression patterns in Hs578T cells, and
      such regulation likely is responsible for the observed isoform-specific changes
      in cell proliferation. Hs578T ER expressing cell-lines provide a unique BC model
      system, permitting the comparison of ERalpha, ERbeta, and ERbetacx actions in the
      same cell-line.

PMID- 17520660
TI  - Increased resistance to trail-induced apoptosis in prostate cancer cells selected
      in the presence of bicalutamide.
AB  - BACKGROUND: Following prolonged treatment with the non-steroidal anti-androgen
      bicalutamide (Casodex), LNCaP cells have become resistant to this drug.
      Previously, we found that the bicalutamide-refractory subline LNCaP-Bic acquires
      a growth advantage and does not respond to androgenic stimulation. In the present
      study, we have asked whether changes in response to the tumor-selective apoptosis
      inducer TNF-related apoptosis-inducing ligand (TRAIL) occur in LNCaP-Bic cells.
      METHODS: LNCaP and LNCaP-Bic cells were incubated with increasing concentrations
      of TRAIL and apoptosis rate was analyzed using FACS. Expression of death
      receptors (DR), adaptor protein Fas-associated death domain (FADD), members of
      the Bcl-2 family, and caspases were investigated by Western blot. RESULTS: The
      percentage of cells undergoing apoptosis was lower in LNCaP-Bic in comparison to
      LNCaP cells. There were no major differences in death receptor expression between
      control LNCaP and bicalutamide-selected cells. Surprisingly, treatment with TRAIL
      increased the levels of Bcl-2 by 50% in LNCaP-Bic cells. The ratio cleaved
      caspase/procaspase-8 was substantially lower in LNCaP-Bic cells. CONCLUSIONS:
      Reduced sensitivity to TRAIL-induced apoptosis is a novel mechanism relevant to
      resistance to bicalutamide in prostate cancer. Inability of TRAIL to cause
      programmed cell death might be caused by multiple perturbations in the TRAIL
      signaling pathway.

PMID- 17520661
TI  - Cost-effectiveness analysis of donepezil for mild to moderate Alzheimer's disease
      in Taiwan.
AB  - BACKGROUND: Donepezil is a drug used for treatment in patients with Alzheimer's
      disease (AD). Information regarding the cost-effectiveness of this medication was
      previously rare in Asia. We used techniques of decision analysis and economic
      evaluation in conjunction with available local epidemiological and clinical data
      on costs of mild to moderate AD to assess the cost-effectiveness of donepezil in
      Taiwan. METHODS: A four-state Markov model was built to simulate the disease
      progression of AD patients. Local transition probabilities and costs of different
      stages were from the studies published earlier. RESULTS: Over a 5-year span,
      donepezil treatment for mild or moderate AD patients is predicted to result in
      the gain of 0.505 QALYs when comparing to usual care, while at the same time
      reducing the cost by US$7,691. The incremental cost was US$3,647 from the payer
      perspective; thus, the incremental cost-effectiveness ratio was estimated to be
      US$7,226 when considering only the medical expenditures. CONCLUSIONS: Under some
      assumptions, donepezil treatment might be a cost saving strategy for mild to
      moderate AD patients in Taiwan from a societal perspective. It is inconclusive
      from the payer's part since we still lack a consensus for judging the cost
      effectiveness of a new health care technology.

PMID- 17520662
TI  - Subjective memory complaints in an elderly sample: a cross-sectional study.
AB  - BACKGROUND: Community based studies show that neurological or psychiatric
      symptoms are very frequent among the elderly population, with poor memory
      complaints being the most common. However, the relationship between poor memory
      complaints and objective memory performance is unclear. We designed this study to
      evaluate whether subjective memory complaints (SMC) are associated with objective
      cognitive performance or depression amongst the elderly Brazilian generation.
      METHODS: A cross-sectional study was carried out in 114 patients who were 50+,
      with or without SMC having no obvious cognitive impairment at its baseline (this
      was screened by the Mini-Mental State Examination with cut-off values adapted
      according to the subjects' educational background). Subjects were assessed
      regarding memory difficulty complaints, demographic data and underwent a
      neuropsychological assessment made up of nine cognitive tests (Rey Auditory
      Verbal Learning Test, Visual Reproduction Test, Logic Memory--History A, Free and
      Cued Selective Reminding Test, Stroop Test, Digit Span, Digit Symbol, Trail
      Making Test, fluency tests: naming animals and fruits) and the Geriatric
      Depression Scale. RESULTS: Twenty-one percent of the subjects had subjective
      memory complaints. The scores in the cognitive assessment of subjects with SMC
      did not differ from the scores of subjects without SMC. However, patients with
      subjective memory complaints had lower scores in the fluency test--category
      animals and the Geriatric Depression Scale. CONCLUSIONS: These results support
      the finding from other cross-sectional studies showing that subjective memory
      complaints are associated with depressive symptoms rather than objective
      cognitive performance.

PMID- 17520663
TI  - Proteomic analysis of cardiomyocytes differentiation in mouse embryonic carcinoma
      P19CL6 cells.
AB  - A clonal derivative named P19CL6 has been isolated from pluripotent P19 mouse
      embryonic carcinoma cells, and this subline efficiently differentiates into
      beating cardiomyocytes when treated with 1% dimethyl sulfoxide (DMSO). It offers
      a valuable model to study cardiomyocytes differentiation in vitro. In this study,
      comparative proteomic analysis was used to characterize the protein profiles
      associated with the DMSO-induced cardiomyocytes differentiation of P19CL6 cells.
      We demonstrated that P19CL6 cells indeed differentiated into cardiomyocytes after
      DMSO inducement as they expressed sarcomeric myosin heavy chain (MHC) as well as
      three cardiac-specific transcription factors (Csx/Nkx-2.5, GATA-4, and MEF2C).
      Image analysis of silver-stained two-dimensional gels was used to find protein
      spots that exhibited an at least 1.5-fold change in abundance after successful
      differentiation. Seventeen protein spots were selected for further analysis by
      matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF-MS)
      and/or nano-electrospray ionization MS/MS (ESI-MS/MS), and 16 protein spots were
      identified. The identified proteins are involved in different cellular functions
      such as metabolism, signal transduction, and cellular organization. To confirm
      the expression changes of the identified proteins during differentiation, the
      mRNA levels of six identified proteins (including seven protein spots) were
      assessed by the real-time polymerase chain reaction and three showed a
      correlation between mRNA level and protein abundance. As an initial step toward
      identifying proteins involved in maintaining the differentiated state of
      cardiomyocytes derived from P19CL6 cells, our data provide some helpful
      information that may lead to a better understanding of the molecular mechanisms
      by which P19CL6 cells differentiate into cardiomyocytes after treatment with
      DMSO.

PMID- 17520664
TI  - Changes in osteoblast, chondrocyte, and adipocyte lineages mediate the bone
      anabolic actions of PTH and small molecule GSK-3 inhibitor.
AB  - Parathyroid hormone (PTH) and glycogen synthase kinase-3 (GSK-3) inhibitor 603281
      31-8, administered once daily increased bone formation in vivo. We investigated
      the molecular mechanisms of the anabolic responses of PTH and 603281-31-8 in rat
      osteopenia model. Female 6-month-old rats were ovariectomized (Ovx) and permitted
      to lose bone for 1 month, followed by treatment with PTH (1-38) at 10
      microg/kg/day s.c. or 603281-31-8 at 3 mg/kg/day p.o. for 60 days. Twenty-four
      hours after the last treatment, RNA from distal femur metaphysis was subjected to
      gene expression analysis. Differentially expressed genes (P<0.05) were subjected
      to pathway analysis to delineate relevant bio-processes involved in skeletal
      biology. Genes involved in morphogenesis, cell growth/differentiation, and
      apoptosis were significantly altered by Ovx and the treatments. Analysis of
      morphogenesis genes showed an overrepresentation of genes involved in
      osteogenesis, chondrogenesis, and adipogenesis. A striking finding was that Ovx
      decreased several markers of osteogenesis/chondrogenesis and increased markers of
      adipogenesis/lipid metabolism. Treatment with either PTH or the GSK-3 inhibitor
      reversed these effects, albeit at different levels. Histological analysis
      confirmed that osteopenia in Ovx animals was associated with three-fold increase
      in marrow adiposity. PTH and GSK-3 inhibitor restored bone volume, and reversed
      or normalized marrow adiposity. Ex vivo studies showed that PTH and GSK-3
      inhibitor increased the ratio of colony forming marrow stromal progenitors (CFU
      fs) that were alkaline phosphatase positive (putative osteoblasts). Our results
      suggest that the bone anabolic actions of PTH and GSK-3 inhibitor in vivo involve
      concerted effects on mesenchymal lineages; osteoblasts, chondrocytes, and
      adipocytes.

PMID- 17520665
TI  - Nanogel-based delivery system enhances PGE2 effects on bone formation.
AB  - Recovery of bone loss is one of the active research issues in bone medicine due
      to the need for efficient measures for bone gain. We examined here a novel drug
      delivery system using a nanogel of cholesterol-bearing pullulan (CHP) in
      combination with prostaglandin E2 (PGE2). PGE2 or PGE2/CHP, vehicle (saline
      containing 0.06% ethanol and 0.02% Tween 80) or CHP were injected on to the
      calvariae of mice once every day for 5 days per week for 4 weeks. Low dosage of
      PGE2 (0.6 microg) alone or CHP alone did not induce new bone formation in this
      system. In contrast, PGE2 (0.6 microg)/CHP induced new bone formation. Bone
      formation activities of PGE2 was enhanced by CHP nanogels only at the site of
      injection (calvaria) but not in the distant sites of the skeleton, showing that
      PGE2/CHP could avoid systemic effects. In spite of the fact that previously
      reported animal models of bone formation by PGE2 were associated with loss of
      body weight, bone formation based on PGE2/CHP did not associate with loss of body
      weight. Furthermore, only a single application of PGE2 in combination with
      nanogel cross-linking hydrogel sphere (PGE2/CHP-PEO) induced new bone formation.
      Thus, nanogel-based delivery system is an efficient delivery system of bone
      anabolic agent, PGE2.

PMID- 17520666
TI  - Antitumor activity of the histone deacetylase inhibitor MS-275 in prostate cancer
      models.
AB  - BACKGROUND: Histone deacetylase (HDAC) inhibitors represent a novel class of
      therapeutic agents with antitumor activity currently in clinical development. In
      this study, we tested the biological effects of the HDAC inhibitor MS-275 in
      various pre-clinical prostate cancer models both in'vitro and in vivo. METHODS:
      In vitro cell proliferation XTT assay and protein expression analysis by Western
      blot were performed. In vivo tumor growth assessment in subcutaneous, orthotopic,
      and transgenic mouse models were conducted. RESULTS: MS-275 significantly
      upregulated histone H3 acetylation and p21 gene expression in human prostate
      cancer cell lines. MS-275 exerted growth arrest in PC-3 and LNCaP cells, and
      induced cell death in DU-145 cells. Prostate specific antigen protein levels were
      increased by MS-275 in LAPC4 cell line. In vivo, MS-275 inhibited the growth of
      DU-145, LNCaP, and PC-3 in subcutaneous xenografts. MS-275 had also a significant
      inhibition of PC-3 cells growth in a mouse intratibial model. Molecular analysis
      showed increased histone acetylation and p21 expression in tumor samples from MS
      275-treated mice. In transgenic adenocarcinoma of mouse prostate (TRAMP) mice,
      long-term treatment of MS-275 slowed the progression of prostate carcinomas with
      significant reduction in cell proliferation. CONCLUSIONS: Taken together, these
      data support the clinical testing of MS-275 for the treatment of prostate cancer.

PMID- 17520667
TI  - The effect of simulated microgravity on osteoblasts is independent of the
      induction of apoptosis.
AB  - Bone loss during spaceflight has been attributed, in part, to a reduction in
      osteoblast number, altered gene expression, and an increase in cell death. To
      test the hypothesis that microgravity induces osteoblast apoptosis and suppresses
      the mature phenotype, we created a novel system to simulate spaceflight
      microgravity combining control and experimental cells within the same in vitro
      environment. Cells were encapsulated into two types of alginate carriers: non
      rotationally stabilized (simulated microgravity) and rotationally stabilized
      (normal gravity). Using these specialized carriers, we were able to culture MC3T3
      E1 osteoblast-like cells for 1-14 days in simulated microgravity and normal
      gravity in the same rotating wall vessel (RWV). The viability of cells was not
      affected by simulated microgravity, nor was the reductive reserve. To determine
      if simulated microgravity sensitized the osteoblasts to apoptogens, cells were
      challenged with staurosporine or sodium nitroprusside and the cell death was
      measured. Simulated microgravity did not alter the sensitivity of C3H10T-1/2 stem
      cells, MC3T3-E1 osteoblast-like cells, or MLO-A5 osteocyte-like cells to the
      action of these agents. RT-PCR analysis indicated that MC3T3-E1 osteoblasts
      maintained expression of RUNX2, osteocalcin, and collagen type I, but alkaline
      phosphatase expression was decreased in cells subjected to simulated microgravity
      for 5 days. We conclude that osteoblast apoptosis is not induced by vector
      averaged gravity, thus suggesting that microgravity does not directly induce
      osteoblast death.

PMID- 17520669
TI  - Underestimation of malignancy of breast core-needle biopsy: concepts and precise
      overall and category-specifc estimates.

PMID- 17520670
TI  - Merkel cell carcinoma: critical review with guidelines for multidisciplinary
      management.
AB  - Merkel cell carcinoma (MCC) is a relatively rare cutaneous malignancy that occurs
      predominantly in the older white population. The incidence of MCC appears to have
      tripled during the past 20 years; an increase that is likely to continue because
      of the growing number of older Americans. The pathogenesis of MCC remains largely
      unknown. However, ultraviolet radiation and immunosuppression are likely to play
      a significant pathogenetic role. Many questions currently remain unanswered
      regarding the biologic behavior and optimal treatment of MCC. Large, prospective,
      randomized studies are not available and are unlikely to be performed because of
      the rarity of the disease. The objective of this review was to provide a
      comprehensive reference for MCC based on a critical evaluation of the current
      data. The authors investigated the importance of sentinel lymph node biopsy as a
      staging tool for MCC to assess the status of the regional lymph node basin and to
      determine the need for additional therapy to the lymph node basin. In an attempt
      to standardize prospective data collection with the intention to define
      prognostic indicators, the authors also present histopathologic profiles for
      primary MCC and sentinel lymph nodes. The controversies regarding the appropriate
      surgical approach to primary MCC, the use of adjuvant radiation therapy, and the
      effectiveness of adjuvant chemotherapy were examined critically. Finally, the
      authors have provided treatment guidelines based on the available evidence and
      their multidisciplinary experience.

PMID- 17520672
TI  - Interferon-gamma regulation of TNFalpha-induced matrix metalloproteinase 3
      expression and migration of human glioma T98G cells.
AB  - Induction of proinflammatory cytokines in response to malignant cells is an
      integral component of immune response to control tumor development. However,
      recent evidences have suggested that tumor cells may evade the immune system and
      exploit inflammatory responses to enhance its own growth. An exemplary example is
      the highly invasive and tumor necrosis factor (TNF)alpha-resistant glioblastoma,
      whose growth is associated with TNFalpha expression. We thus examined whether the
      tumor takes advantage of TNFalpha overexpression to enhance its invasiveness. To
      delineate the contribution of inflammation in tumor migration, we demonstrated
      that the role of proinflammatory cytokines on matrix metalloproteinases-3 (MMP-3)
      expression, and its consequent effects on the invasiveness of a human glioma cell
      line, T98G. By using Matrigel Invasion Chamber, T98G cell migration was
      significantly enhanced in response to TNFalpha. In contrast, interferon-gamma
      (IFN gamma) reduced both basal and TNFalpha-enhanced cell invasion. To
      investigate the mechanisms involved, we demonstrated that TNFalpha upregulated
      mRNA and protein expression of MMP-3 in T98G cells, whereas IFN gamma
      downregulated the MMP-3 expression. The role of MMP-3 in glioma invasiveness was
      further confirmed by transfecting MMP-3 siRNA in T98G to abrogate the TNFalpha
      enhanced cell invasion. To delineate the mechanisms further, we showed that IFN
      gamma exerts an inhibitory effect on the binding of TNFalpha-activated Ets-1 and
      NF kappa B to their respective enhancer elements found in MMP-3 promoter. In
      summary, our results indicated that TNFalpha enhances the invasiveness of T98G
      glioma cells through MMP-3 induction, and such enhancement of cell migration can
      be inhibited by IFN gamma.

PMID- 17520673
TI  - Methylseleninic acid enhances the effect of etoposide to inhibit prostate cancer
      growth in vivo.
AB  - New therapeutic agents are needed for the treatment of androgen-independent
      prostate cancer (PrCa). We have investigated the effect of methylseleninic acid
      (MSA) on tumor stage-specific prostate cells derived from the C3 (1)/Tag model
      for PrCa: Pr111, a slow-growing and nontumorigenic cell line isolated from a
      prostate intraepithelial neoplasia lesion; Pr14, a tumorigenic line derived from
      a primary tumor; and Pr14C1, a sub-clone of Pr14 explanted from a lung
      metastasis. We demonstrate that MSA strongly inhibits cell growth and induces
      apoptosis in C3 (1)/Tag tumor cells, in a dose-dependent manner. A decrease in
      phosphorylated ERK1/2 and AKT was also found in tumor cells, but not in Pr111.
      Microarray analysis using affymetrix showed that the number of genes with an
      altered expression in tumor cells is significantly higher (p < 0.01) than in
      nontumoral cells. Pathways analyses revealed a decrease in the expression of
      genes involved in metabolism (Fabp5, Cyba), signal transduction (ERK, AKT),
      angiogenesis (neuropilin-1, Flt-4) and transcription (cAMP response element
      binding protein) in tumor cells. The expression of neuropilin-1, a protein
      involved in VEGF signaling and tumor angiogenesis, was 97-fold repressed in Pr14
      cells treated with MSA. Combination treatments using low doses of etoposide or
      taxotere (docetaxel), plus low doses of MSA revealed a strong enhancement of cell
      growth inhibition and apoptosis in tumor cells. Our in vivo studies using Pr14
      cells xenografted into nude mice demonstrated that MSA significantly enhances the
      chemotherapeutical effect of etoposide, resulting in 78.3% tumor growth
      inhibition. These results suggest that MSA could be used against PrCa to enhance
      the effect of etoposide.

PMID- 17520674
TI  - The combined actions of NK and T lymphocytes are necessary to reject an EGFP+
      mesenchymal tumor through mechanisms dependent on NKG2D and IFN gamma.
AB  - Better understanding of the mechanisms that mediate spontaneous immune rejections
      ought to be important in the quest for improvements in immunotherapy of cancer. A
      set of intraperitoneal tumors of mesenchymal origin that had been chemically
      induced in ubiquitously expressing EGFP transgenic mice provided a model in which
      both T and NK cells were absolutely required for tumor rejection. Tumor cells
      were traceable because of being fluorescent and readily grafted in RAG1(-/-)
      immunodeficient mice, whereas they were rejected in a majority of syngeneic
      C57BL/6 and EGFP-transgenic mice. Tumor-cell clones with the highest EGFP
      expression tended to be rejected, but a direct involvement of EGFP as the antigen
      recognized for the immune rejections was ruled out. Rejections were absolutely
      dependent on NK cells as well as on CD4(+) and CD8(+) T lymphocytes according to
      selective depletion studies. Furthermore, CD8(+) and CD4(+) T lymphocytes as well
      as NK cells were detected in the inflammatory infiltrate that mediates tumor
      rejection along with some DC. The effects of IFN gamma, produced at the tumor
      site by T and NK lymphocytes, were only required at the malignant cell level and
      were necessary for tumor eradication. NK recognition of tumor cells was mediated
      by the NKG2D-activating receptor and blocking its function in vivo partially
      interfered with rejection. Therefore, complete rejection of these mesenchymal
      tumors requires a concerted set of activities including direct tumor-cell
      destruction and IFN gamma production that are mediated by both NK and T cells.

PMID- 17520675
TI  - Artesunate attenuates the growth of human colorectal carcinoma and inhibits
      hyperactive Wnt/beta-catenin pathway.
AB  - Artesunate (ART), a remarkable antimalarial agent, also inhibited the growth of
      human colorectal carcinoma. As determined by MTT assay, flow cytometry analysis
      on apoptosis and indirect immunofluorescence analysis on the proliferation
      associated marker Ki67, ART suppressed the proliferation and promoted the
      apoptosis of colorectal cancer cells in a dose-dependent manner. Furthermore,
      immunofluorescence analysis on beta-catenin and RT-PCR analysis on Wnt/beta
      catenin target genes demonstrated ART translocated beta-catenin from nucleus to
      adherent junctions of membrane and reduced transcription mediated by beta
      catenin. These results suggested the anticancer activity of ART correlated with
      the inhibition of hyperactive Wnt/beta-catenin signaling pathway. In vivo, ART
      significantly slowed the growth of colorectal tumor xenografts. Bioluminescent
      imaging also revealed that ART decreased the physiological activity of tumor
      xenografts and delayed spontaneous liver metastasis. These antitumor effects were
      related to the membranous translocation of beta-catenin and the inhibition of the
      unrestricted activation of Wnt/beta-catenin pathway, which was confirmed by the
      immunohistochemical staining of tumor tissues. These results and the known low
      toxicity are clues that ART might be a promising candidate drug for the treatment
      of colorectal carcinoma.

PMID- 17520676
TI  - Cyclin-dependent kinase inhibitor, flavopiridol, induces apoptosis and inhibits
      tumor growth in drug-resistant osteosarcoma and Ewing's family tumor cells.
AB  - Multimodal therapies play important roles in the treatment of osteosarcoma (OS)
      and Ewing's family of tumors (EFTs), two most frequent malignant bone tumors.
      Although the clinical outcome of primary OS and EFTs is greatly improved, the
      relapsed cases often are associated with multidrug resistance of the tumors and
      the prognosis of these patients is still poor. Flavopiridol, a pan cyclin
      dependent kinase (CDK) inhibitor is a novel antitumor agent that can induce cell
      cycle arrest and apoptosis in many cancer cells. However, there have been no
      studies about the effects of flavopiridol on drug-resistant OS and EFTs. Here, we
      demonstrated that flavopiridol induced the cleavage of poly-ADP-ribose polymerase
      (PARP) in a time and dose dependent manner in adriamycin-resistant OS and EFTs
      cells expressing P-glycoprotein (P-gp) and multidrug resistance-associated
      protein 1 (MRP(1)) as effectively as in their parental cells. Our data also
      showed that flavopiridol caused the release of mitochondrial cytochrome c and the
      activation of caspase-9, caspase-8 and caspase-3, with an increase ratio of the
      proapoptotic protein level (Bax) to the antiapoptotic protein level (Bcl-2 and
      Bcl-X(L)), while apoptosis was inhibited by pan caspase inhibitor (Z-VAD-FMK) and
      caspase-3 inhibitor (Z-DEVD-FMK), not by caspase-8 inhibitor (Z-IETD-FMK). The
      treatment with flavopiridol further inhibited the tumor growth in mouse models of
      the drug-resistant OS and EFTs. These results suggest that flavopiridol might be
      promising in clinical therapy for the relapsed OS and EFTs.

PMID- 17520677
TI  - Increased HIF1 alpha in SDH and FH deficient tumors does not cause microsatellite
      instability.
AB  - Germline mutations in nuclear genes encoding mitochondrial enzymes fumarate
      hydratase (FH) and succinate dehydrogenase (subunits SDHB/C/D) have been
      implicated in the development of tumor syndromes referred to as hereditary
      leiomyomatosis and renal cell cancer (HLRCC) and hereditary paragangliomatosis
      (HPGL), respectively. FH and SDH are operating in the tricarboxylic acid cycle
      (the TCA cycle, the Krebs cycle). In the FH and SDH deficient tumors,
      accumulation of the substrates, fumarate and succinate, has been shown to cause
      stabilization of hypoxia inducible factor 1 alpha (HIF1 alpha). According to
      recent studies, HIF1 alpha could contribute to the hypoxia induced genomic
      instability seen in many cancers, through repression of mismatch repair (MMR)
      protein MSH2. In this study, in agreement with previous works, we found HIF1
      alpha to be moderately or highly stabilized in 67% (16/24) and 77% (48/62) of
      HLRCC tumors and SDHB/C/D paragangliomas (PGL) and pheochromocytomas (PHEO),
      respectively. In addition, a set of 54 other familial and nonfamilial PGLs/PHEOs
      were studied. Moderately or highly stabilized HIF1 alpha was present in 68%
      (26/38) of the PGLs but in PHEOs (n = 16) no such pattern was observed. We then
      analyzed the suggested link between HIF1 alpha stabilization and MSH2 repression,
      in HLRCC and HPGL tumor material. No microsatellite instability (MSI) or lack of
      MSH2 expression was, however, observed. Thus we failed to provide in vivo
      evidence for the proposed link between HIF1 alpha stabilization and functional
      MMR deficiency, in TCAC deficient tumors.

PMID- 17520678
TI  - Transforming properties of TC-1 in human breast cancer: interaction with FGFR2
      and beta-catenin signaling pathways.
AB  - Breast cancer development is associated with gene amplification and over
      expression that is believed to have a causative role in oncogenesis. Previous
      studies have demonstrated that over expression of TC-1(C8orf4) mRNA occurs in
      approximately 50% of breast cancer cell lines and primary tumor specimens. Here,
      we show that TC-1 has transforming properties in human mammary epithelial (HME)
      cells and its expression is mechanistically linked to FGFR signaling cascades. In
      vitro experiments demonstrate that TC-1 over expression mediates both anchorage
      independent and growth factor-independent proliferation of HME cells. TC-1 was
      down regulated by the FGFR inhibitor PD173074 in the breast cancer cell line SUM
      52 that also has an FGFR2 gene amplification and over expression. Furthermore,
      forced expression of FGFR2 in HME cells increased the level of expression of
      endogenous TC-1 mRNA. TC-1 has been implicated as a modulator of Wnt/beta-catenin
      signaling in 293 cells and in gastric cancer cells. However, while we did find
      increased expression of a subset of beta-catenin target genes in TC-1 over
      expressing cells, we did not find an association of TC-1 with global expression
      of beta-catenin target genes in our cells. Taken together, our data suggest that
      TC-1 over expression is transforming and may link with the FGFR pathway in a
      subset of breast cancer.

PMID- 17520679
TI  - IGF-I and mammographic density in four geographic locations: a pooled analysis.
AB  - Insulin-like growth factor (IGF-I) and prolactin have been found to be associated
      with breast cancer risk and with mammographic density. In a pooled analysis from
      4 geographic locations, we investigated the association of percent mammographic
      density with serum levels of IGF-I, IGFBP-3 and prolactin. The pooled data set
      included 1,327 pre- and postmenopausal women: Caucasians from Norway, Arizona and
      Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians
      from Hawaii. Serum samples were assayed for IGF-I, IGFBP-3 and prolactin levels
      using ELISA assays. Mammographic density was quantified using a computer-assisted
      density method. After stratification by menopausal status, multiple regression
      models estimated the relation between serum analytes and breast density. All
      serum analytes except prolactin among postmenopausal women differed significantly
      by location/ethnicity group. Among premenopausal subjects, IGF-I levels and the
      molar ratio were highest in Hawaii, intermediate in Japan and lowest in Arizona.
      For IGFBP-3, the order was reversed. Among postmenopausal subjects, Norwegian
      women had the highest IGF-I levels and women in Arizona had the lowest while
      women in Japan and Hawaii had intermediate levels. We observed no significant
      relation between percent density and IGF-I or prolactin levels among pre-and
      postmenopausal women. The significant differences in IGF-I levels by location but
      not ethnicity suggest that environmental factors influence IGF-I levels, whereas
      percent breast density varies more according to ethnic background than by
      location. Based on this analysis, the influence of circulating levels of IGF-I,
      IGFBP-3, and prolactin on percent density appears to be very small.

PMID- 17520680
TI  - Roles of lytic viral infection and IL-6 in early versus late passage
      lymphoblastoid cell lines and EBV-associated lymphoproliferative disease.
AB  - Lytically infected EBV-positive lymphoblastoid cells enhance the growth of early
      passage, but not late-passage, EBV-immortalized lymphoblastoid cell lines (LCLs)
      in SCID mice and have enhanced IL-6 secretion. Here, we have examined the
      importance of IL-6 for the growth of early-passage LCLs (EPL) in SCID mice,
      identified lytic EBV proteins that activate IL-6 production and compared viral
      and cellular differences between early versus late passage LCLs (LPL). IL-6 was
      required for efficient growth of EPL in SCID mice. The EBV immediate-early (IE)
      proteins, BRLF1 and BZLF1, each induced IL-6 secretion when transfected into 293
      and BJAB cells. Interestingly, the combination of BZLF1 and the latent EBV
      protein, LMP-1, induced much more IL-6 expression in both 293 and BJAB cells than
      either protein alone. Both BZLF1 and BRLF1 also enhanced IL-10 production in 293
      cells. In comparison to the EPL, LPL had much reduced expression of early lytic
      viral proteins and cellular IL-6. In contrast, expression of cellular IL-10 was
      similar in EPL versus LPL, while VEGF secretion was increased in late-passage
      LCLs. These results suggest that both BRLF1 and BZLF1 contribute to IL-6
      secretion in lytically infected cells and that lytically infected cells may
      promote early lymphoproliferative disease in patients through enhanced IL-6
      production.

PMID- 17520681
TI  - Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori
      eradication prior to incomplete intestinal metaplasia.
AB  - Loss of Sonic Hedgehog (Shh) and aberrant CDX2 expression are early changes
      correlating with the presence of intestinal metaplasia that occur in the gastric
      mucosa prior to neoplastic transformation. The aim of this study was to compare
      the improvement in corpus gastritis with Shh and CDX2 expression after H. pylori
      eradication between subjects at high risk for gastric cancer and controls. The
      usefulness of serum pepsinogen levels as a predictor of resolved corpus gastritis
      was also examined. Seventy patients with endoscopic resection for early gastric
      cancer and 30 controls were studied. Expression of Shh and CDX2 were evaluated by
      immunostaining. Serum levels of pepsinogen I before eradication in the patients
      scored as having improvement of corpus atrophy were significantly higher than in
      the patients without improvement (<0.01). Residual inflammation at the corpus
      lesser curve was more frequently detected in the cancer group than in the
      controls (OR 4.6 95% C.I. 1.6-13.5) and in the mucosa with incomplete intestinal
      metaplasia rather than in those without incomplete intestinal metaplasia (OR 7.6
      95% C.I. 2.4-24.3). Atrophy, expression of Shh and CDX2 at the corpus lesser
      curve significantly improved in mucosa without incomplete intestinal metaplasia
      (p < 0.01), but not in mucosa with incomplete intestinal metaplasia. In
      conclusion, H. pylori eradication prior to development of incomplete intestinal
      metaplasia improves corpus gastritis and may prevent gastric cancer. Pepsinogen I
      may be a useful marker in patients with a residual higher risk of gastric cancer
      after H. pylori eradication.

PMID- 17520682
TI  - Promoter methylation as a common mechanism for inactivating E-cadherin in human
      salivary gland adenoid cystic carcinoma.
AB  - BACKGROUND: The role of promoter methylation in the inactivation of E-cadherin (E
      cad) in salivary gland adenoid cystic carcinoma (ACC) is unknown. The objective
      of this study was to determine the role and potential clinical implications of
      promoter methylation of E-cad in salivary gland ACC. METHODS: The promoter
      methylation status of E-cad was determined by using methylation-specific
      polymerase chain reaction (PCR) analysis in 60 primary salivary gland ACC tissues
      and 3 ACC cell lines. The level of E-cad protein expression was determined by
      immunohistochemical analysis of each tumor. E-cad protein and messenger RNA
      (mRNA) expression levels were examined by immunohistochemical analysis and
      reverse transcriptase-PCR in 3 ACC cell lines. Associations between molecular
      alterations and patients' clinicopathologic characteristics were analyzed
      statistically. E-cad mRNA expression was examined in a 5-azacytidine-treated ACC
      2 cell line. RESULTS: Promoter methylation of E-cad was detected in 34 of 60
      tumors (57%). Of those 34 tumors, 18 tumors (53%) showed no E-cad protein
      expression, whereas only 5 of the remaining 26 tumors (19%) without E-cad
      promoter methylation showed no E-cad protein expression (P = .01). Tumors that
      had E-cad promoter methylation had a significantly higher histologic grade (P =
      .01) and more perineural invasion (P = .02) compared with tumors that did not
      have methylation. All 3 ACC cell lines exhibited E-cad promoter methylation and a
      lack of E-cad mRNA and protein expression, whereas 5-azacytidine restoredE-cad
      mRNA expression in the ACC-2 cell line. CONCLUSIONS: E-cad frequently is
      inactivated in salivary gland ACC through promoter methylation, and E-cad
      promoter methylation may play a role in tumor cell differentiation and perineural
      invasion.

PMID- 17520683
TI  - Prognostic significance of CD100 expression in soft tissue sarcoma.
AB  - BACKGROUND: CD100, a class IV semaphorin, promotes angiogenesis, invasive growth,
      proliferation, and antiapoptosis of cancer cells in vitro. The expression of
      CD100 in soft tissue sarcoma (STS) and its correlation with clinicopathologic
      factors and prognostic significance were evaluated. METHODS: Expression levels of
      CD100 in patients with localized STS were evaluated immunohistochemically on
      paraffin-embedded sections from 81 patients, including 47 men and 34 women with a
      median age of 54 years. Staining intensity was categorized into weaker than
      (level 1) or equal to that of lymphocytes with a rate of <10% stained tumor cells
      (level 2) or >10% stained tumor cells (level 3). Ki-67 staining was performed in
      parallel. RESULTS: Forty-two tumors (52%) had level 1 CD100 expression, 18 tumors
      (22%) had level 2 CD100 expression, and 21 tumors (26%) had level 3 CD100
      expression. Tumors that had level 2 and 3 CD100 expression were correlated
      significantly with higher mitotic count, cellularity, ratio of necrosis, and Ki
      67 labeling index (LI) compared with tumors that had level 1 CD100 expression.
      There was no correlation between CD100 expression and other characteristics.
      Among the 3 levels of CD100 expression, higher expression levels were correlated
      with poorer overall and disease-free survival. Multivariate analysis revealed
      that CD100 expression (levels 1 and 2 vs level 3) and tumor size (<or=5 cm vs >5
      cm) were independent prognosticators for overall survival (P < .05 for both), and
      CD100 expression (levels 1 and 2 vs level 3) was an independent prognosticator
      for disease-free survival (P < .05). CONCLUSIONS: The results from this study
      indicated the demonstrated prognostic significance of CD100 expression in STS.

PMID- 17520685
TI  - A rapid mass spectrometric strategy for the characterization of N- and O-glycan
      chains in the diagnosis of defects in glycan biosynthesis.
AB  - Glycosylation of proteins is a very complex process which involves numerous
      factors such as enzymes or transporters. A defect in one of these factors in
      glycan biosynthetic pathways leads to dramatic disorders named congenital
      disorders of glycosylation (CDG). CDG can affect the biosynthesis of not only
      protein N-glycans but also O-glycans. The structural analysis of glycans on serum
      glycoproteins is essential to solving the defect. For this reason, we propose in
      this paper a strategy for the simultaneous characterization of both N- and O
      glycan chains isolated from the serum glycoproteins. The serum (20 microL) is
      used for the characterization of N-glycans which are released by enzymatic
      digestion with PNGase F. O-glycans are chemically released by reductive
      elimination from whole serum glycoproteins using 10 microL of the serum. Using
      strategies based on mass spectrometric analysis, the structures of N- and O
      glycan chains are defined. These strategies were applied on the sera from one
      patient with CDG type IIa, and one patient with a mild form of congenital
      disorder of glycosylation type II (CDG-II) that is caused by a deficiency in the
      Cog1 subunit of the complex.

PMID- 17520686
TI  - Differential expression of both extracellular and intracellular proteins is
      involved in the lethal or nonlethal phenotypic variation of BrtlIV, a murine
      model for osteogenesis imperfecta.
AB  - This study used proteomic and transcriptomic techniques to understand the
      molecular basis of the phenotypic variability in the bone disorder osteogenesis
      imperfecta (OI). Calvarial bone mRNA expression was evaluated by microarray, real
      time, and comparative RT-PCR and the bone proteome profile was analyzed by 2-DE,
      MS, and immunoblotting in the OI murine model BrtlIV, which has either a moderate
      or a lethal OI outcome. Differential expression analysis showed significant
      changes for eight proteins. The expression of the ER stress-related protein
      Gadd153 was increased in lethal mice, whereas expression of the chaperone alphaB
      crystallin was increased in nonlethal mice, suggesting that the intracellular
      machinery is involved in the modulation of the OI phenotype. Furthermore, in
      lethal BrtlIV, the increased expression of the cartilaginous proteins Prelp,
      Bmp6, and Bmp7 and the lower expression of the bone matrix proteins matrilin 4,
      microfibril-associated glycoprotein 2, and thrombospondin 3 revealed that both a
      delay in skeletal development and an alteration in extracellular matrix
      composition influence OI outcomes. Differentially expressed proteins identified
      in this model offer a starting point for elucidating the molecular basis of
      phenotypic variability, a characteristic common to many genetic disorders. The
      first reference 2-DE map for murine calvarial tissue is also reported.

PMID- 17520687
TI  - Cell cycle dependent phosphorylation and subnuclear organization of the histone
      gene regulator p220(NPAT) in human embryonic stem cells.
AB  - Human embryonic stem (ES) cells have an expedited cell cycle ( approximately 15
      h) due to an abbreviated G1 phase ( approximately 2.5 h) relative to somatic
      cells. One principal regulatory event during cell cycle progression is the G1/S
      phase induction of histone biosynthesis to package newly replicated DNA. In
      somatic cells, histone H4 gene expression is controlled by CDK2 phosphorylation
      of p220(NPAT) and localization of HiNF-P/p220(NPAT) complexes with histone genes
      at Cajal body related subnuclear foci. Here we show that this 'S point' pathway
      is operative in situ in human ES cells (H9 cells; NIH-designated WA09).
      Immunofluorescence microscopy shows an increase in p220(NPAT) foci in G1
      reflecting the assembly of histone gene regulatory complexes in situ. In contrast
      to somatic cells where duplication of p220(NPAT) foci is evident in S phase, the
      increase in the number of p220(NPAT) foci in ES cells appears to precede the
      onset of DNA synthesis as measured by BrdU incorporation. Phosphorylation of
      p220(NPAT) at CDK dependent epitopes is most pronounced in S phase when cells
      exhibit elevated levels of cyclins E and A. Our data indicate that subnuclear
      organization of the HiNF-P/p220(NPAT) pathway is rapidly established as ES cells
      emerge from mitosis and that p220(NPAT) is subsequently phosphorylated in situ.
      Our findings establish that the HiNF-P/p220(NPAT) gene regulatory pathway
      operates in a cell cycle dependent microenvironment that supports expression of
      DNA replication-linked histone genes and chromatin assembly to accommodate human
      stem cell self-renewal.

PMID- 17520688
TI  - Complement 3 is involved in changing the phenotype of human glomerular mesangial
      cells.
AB  - Complement activation contributes to tissue injury in various forms of
      glomerulopathy and is characterized by deposition of complement components, which
      accelerates the progression of chronic renal damage. We recently reported that
      complement 3 (C3), a critical component of the complement system, is associated
      with the synthetic phenotype of vascular smooth muscle cells. It is possible that
      C3 stimulates mesangial cells to assume the synthetic phenotype to, in turn,
      induce glomerular injury and sclerosis. We investigated the role of C3 in the
      growth and phenotype of mesangial cells. Cultured human mesangial cells (HMCs)
      expressed C3 mRNA and protein, and levels were increased in response to IFN-gamma
      and TNF-alpha. HMCs also expressed C3a receptor mRNA and protein. Exogenous C3a
      stimulated DNA synthesis in HMCs in a dose-dependent manner. C3a decreased
      expression h-caldesmon mRNA, a marker of the contractile phenotype, and increased
      the expression of osteopontin, matrix Gla, and collagen type1 alpha1 (collagen
      IV) mRNAs, which are markers of the synthetic phenotype. C3a decreased expression
      of alpha-smooth muscle actin in HMCs. Small interfering RNA (siRNA) targeting C3
      reduced the DNA synthesis and proliferation of HMCs, increased expression of h
      caldesmon mRNA, and decreased expression of osteopontin, matrix Gla, and collagen
      IV mRNAs in HMCs. These results indicate that C3 causes HMCs to convert to the
      synthetic phenotype and stimulates growth of mesangial cells, suggesting that C3
      may play an important role in phenotypic regulation of mesangial cells in renal
      diseases.

PMID- 17520689
TI  - Resistance to 1,25D-induced differentiation in human acute myeloid leukemia HL60
      40AF cells is associated with reduced transcriptional activity and nuclear
      localization of the vitamin D receptor.
AB  - The anti-neoplastic effects of 1,25-dihydroxyvitamin D3 (1,25D) are well
      documented in numerous tumor cell systems and animal models of cancer. However,
      despite this pre-clinical success, the clinical use of 1,25D is currently impeded
      by the dose-limiting hypercalcemia, and the risk of development of resistance to
      1,25D. In this study, we investigated the mechanism of resistance to 1,25D of
      HL60-40AF cells, a model of drug-resistant acute myeloid leukemia, derived from
      HL60 cells by cultivation in the presence of 1,25D. The data indicate that
      transcriptional activity of vitamin D receptor (VDR) in 40AF cells increases only
      briefly when the cells are treated with 1,25D, despite greater basal cellular
      levels of VDR protein in the resistant than in the 1,25D-sensitive cells.
      Analysis of the 40AF VDR mRNA sequence indicated alterations in the 5'
      untranslated region (UTR), but coding domain variations were not observed. When
      resistance to 1,25D-induced differentiation of 40AF cells was reversed by a
      combination of 1,25D with potentiators of differentiation (plant derived
      antioxidants and a p38MAPK inhibitor), an increase in the level of nuclear VDR,
      as well as an increase in CYP24 mRNA expression was observed. These data suggest
      that decreased ability of 1,25D to induce VDR nuclear localization and the
      consequent VDR target gene transcription may be an important reason for the
      resistance of 40AF cells to 1,25D. Further, our data show that VDR localization
      and phosphorylation can be increased by combining 1,25D with potentiators of
      differentiation. Analysis of the mechanisms that underlie the reduction and
      potentiation of 1,25D-mediated changes in VDR activity may lead to the
      identification of new cellular targets that enhance 1,25D-induced monocytic
      differentiation.

PMID- 17520690
TI  - Early replication and the apoptotic pathway.
AB  - In higher eukaryotes there is a link between time of replication and
      transcription. It is generally accepted that genes that are actively transcribed
      are replicated in the first half of S phase while inactive genes replicate in the
      second half of S phase. We have recently reported that in normal human
      fibroblasts there are some functionally related genes that replicate at the same
      time in S phase. This had been previously reported for functionally related genes
      that are located in clusters, for example the alpha- and beta-globin complexes.
      We have shown, however, that this also occurs with some functionally related
      genes that are not organized in a cluster, but rather are distributed throughout
      the genome. For example, using GOstat analysis of data from our and other groups,
      we found an overrepresentation of genes involved in the apoptotic process among
      sequences that are replicated very early (approximately in the first hour of S
      phase) in both fibroblasts and lymphoblastoid cells. This finding leads us to
      question how and why the replication of genes in the apoptotic pathway is
      temporally organized in this manner. Here we discuss the possible explanations
      and implications of this observation.

PMID- 17520691
TI  - Decomposing the autism phenotype into familial dimensions.
AB  - The objective of this article is to decompose the level of functioning phenotype
      in autism to see if it can be conceptualized as two simpler, but still familial,
      dimensional phenotypes of language and non-verbal IQ. We assembled 80 sibpairs
      with either autism, Asperger syndrome or atypical autism. To see whether the
      familial correlation on language scores was accounted for by the familial
      correlation on non-verbal IQ, residual language scores were calculated for each
      member of the sibpair based on a multiple regression equation using their IQ
      score as an explanatory or independent variable and controlling for the age and
      gender of the affected individual. These residual scores were then used to
      calculate intraclass correlations between affected sibs. This process was
      repeated using IQ as the dependent variable and language as a covariate. Within
      affected individuals there was a strong relation between non-verbal IQ (as
      measured by the Leiter performance scale) and language (as measured by the
      Vineland Communication Scale). In addition, there was familial correlation
      between sibs on both measures. Evidence of familial aggregation on both non
      verbal IQ and language remained even after partialling out the effect of the
      covariates by regression analysis and by generalized estimating equation. These
      findings suggest that non-verbal IQ and language in PDD may arise from
      independent genetic mechanisms. The implications of this finding for linkage
      analysis and for identifying genetically informative phenotypes are discussed.

PMID- 17520692
TI  - Molecularly targeted therapy for malignant glioma.
AB  - Malignant gliomas are relatively uncommon but lethal cancers. Despite recent
      research efforts in cancer therapy, the prognosis of patients with malignant
      gliomas has remained dismal. Understanding the molecular pathogenesis of glioma
      may lead to a rational development of new therapies. Despite the genetic
      heterogeneity of malignant gliomas, common aberrations in the signaling elements
      of the growth and survival pathways are found. New treatments have emerged to
      target molecules in these signaling pathways with the goal to increase specific
      efficacy and minimize toxicity. Monoclonal antibodies and low molecular-weight
      kinase inhibitors are the most common classes of agents in targeted cancer
      treatment. Most clinical trials of these agents as monotherapies have failed to
      demonstrate survival benefit in unselected malignant glioma patient populations.
      Several mechanisms of treatment failure have been demonstrated. In response,
      multitargeted kinase inhibitors and combinations of single-targeted kinase
      inhibitors have been developed to overcome therapeutic resistance. In addition,
      multimodality combinations of targeted agents with radiation, chemotherapy, or
      immunotherapy/vaccines may enhance treatment efficacy. Future development of
      these agents will require advances in discovery and validation of new molecular
      targets, improvement of therapeutic delivery, and identification of correlative
      biomarkers. Novel clinical trial designs and endpoints may increase the
      efficiency of new drug evaluation. In this review, the authors discussed the
      current understanding of molecular pathogenesis and the development of
      molecularly targeted therapies in malignant glioma.

PMID- 17520693
TI  - First evidence of the presence of chitin in skeletons of marine sponges. Part II.
      Glass sponges (Hexactinellida: Porifera).
AB  - Sponges (Porifera) are presently gaining increased scientific attention because
      of their secondary metabolites and specific skeleton structures. In contrast to
      demosponges, whose skeletons are formed from biopolymer spongin, glass sponges
      (hexactinellids) possess silica-organic composites as the main natural material
      for their skeletal fibres. Chitin has a crystalline structure and it constitutes
      a network of organized fibres. This structure confers rigidity and resistance to
      organisms that contain it, including monocellular (yeast, amoeba, diatoms) and
      multicellular (higher fungi, arthropods, nematodes, molluscs) organisms. In
      contrast to different marine invertebrates whose exoskeletons are built of
      chitin, this polysaccharide has not been found previously as an endogenous
      biopolymer within glass sponges (Hexactinellida). We hypothesized that glass
      sponges, which are considered to be the most basal lineage of multicellular
      animals, must possess chitin. Here, we present a detailed study of the structural
      and physico-chemical properties of skeletal fragments of the glass sponge Farrea
      occa. We show that these fibres have a layered design with specific compositional
      variations in the chitin/silica composite. We applied an effective approach for
      the demineralization of glass sponge skeletal formations based on an etching
      procedure using alkali solutions. The results show unambiguously that alpha
      chitin is an essential component of the skeletal structures of Hexactinellida.
      This is the first report of a silica-chitin's composite biomaterial found in
      nature. From this perspective, the view that silica-chitin scaffolds may be key
      templates for skeleton formation also in ancestral unicellular organisms, rather
      than silica-protein composites, emerges as a viable alternative hypothesis.

PMID- 17520694
TI  - Antioxidants slow photoreceptor cell death in mouse models of retinitis
      pigmentosa.
AB  - Retinitis pigmentosa (RP) is a heterogeneous group of diseases in which one of a
      wide variety of mutations selectively causes rod photoreceptor cell death. After
      rods die, cone photoreceptors gradually die resulting in blindness. Antioxidants
      reduce cone cell death in rd1/rd1 mice indicating that cones die from oxidative
      damage in that model of rapidly progressive RP. In this study, we sought to
      determine if this observation could be generalized to models of other types of
      RP, rd10/rd10 mice, a model of more slowly progressive recessive RP, and Q344ter
      mice, a model of rapidly progressive dominant RP. Compared to appropriate vehicle
      treated controls, rd10/rd10 and Q344ter mice treated between P18 and P35 with a
      mixture of antioxidants previously found to be effective in rd1/rd1 mice showed
      significantly greater cone survival. Antioxidant-treated rd10/rd10 mice showed
      preservation of cone function as shown by a significant increase in photopic ERG
      b-wave amplitudes, and surprisingly showed temporary preservation of scotopic a
      wave amplitudes, prolonged rod survival, and slowed depletion of rhodopsin mRNA.
      These data suggest that oxidative damage contributes to cone cell death
      regardless of the disease causing mutation that leads to the demise of rods, and
      that in more slowly progressive rod degenerations, oxidative damage may also
      contribute to rod cell death. Protection from oxidative damage may be a broadly
      applicable treatment strategy in RP.

PMID- 17520695
TI  - AFAP-110 is required for actin stress fiber formation and cell adhesion in MDA-MB
      231 breast cancer cells.
AB  - Regulation of actin organization and dynamics is a highly complex process that
      involves a number of actin-binding proteins, including capping, branching,
      severing, sequestering, and cross-linking proteins. The actin-binding and cross
      linking protein AFAP-110 is expressed in normal myoepithelial cells. Screening of
      different breast epithelial cell lines revealed high expression levels of AFAP
      110 in the human breast cancer cell lines MDA-MB-231 and MDA-MB-435. Knockdown of
      AFAP-110 expression in MDA-MB-231 cells does not result in any changes in cell
      proliferation but did result in a loss of actin stress fiber cross-linking and
      decreased adhesion to fibronectin. An inducible knockdown approach confirms that
      MDA-MB-231 breast cancer cells require AFAP-110 expression for stress fiber
      formation and adhesion. Thus, AFAP-110 may provide cytoskeletal tension through
      stress fiber formation, which is required for focal adhesion formation. Indeed,
      we could not detect any focal contacts or focal adhesions in AFAP-110 knockdown
      cells after adhesion to fibronectin. Although expression levels of crucial focal
      adhesion components were not influenced by AFAP-110 expression levels, treatment
      of AFAP-110 knockdown cells with LPA did not result in induction of actin stress
      fibers and focal adhesions. In summary, AFAP-110 plays an important role in MDA
      MB-231 breast cancer cell adhesion possibly by regulating stress filament cross
      linking which would promote focal adhesion formation.

PMID- 17520696
TI  - Suppression by glutamate of proliferative activity through glutathione depletion
      mediated by the cystine/glutamate antiporter in mesenchymal C3H10T1/2 stem cells.
AB  - Although previous studies including ours have demonstrated the functional
      expression of different glutamate (Glu) signaling machineries such as Glu
      receptors (GluRs) and transporters in osteoblasts and chondrocytes, little
      attention has been paid to the role of Glu in their ancestral mesenchymal stem
      cells to date. In the present study, we have evaluated the possible functionality
      of Glu in cultured mouse mesenchymal stem cell line C3H10T1/2 cells endowed to
      proliferate for the self-renewal and to differentiate toward osteoblast,
      chondrocyte, adipocyte, and myocyte lineages. Expression of mRNA was for the
      first time shown with the cystine/Glu antiporter composed of xCT and 4F2hc
      subunits, in addition to particular excitatory amino acid transporter (EAAT)
      isoforms and ionotropic GluRs, in undifferentiated C3H10T1/2 cells. Glu
      significantly suppressed the proliferation activity at a concentration over 500
      microM without inducing cell death or differentiation, while the suppression
      occurred in a manner sensitive to the prevention by cystine and reduced
      glutathione (GSH), but not by EAAT inhibitors. A significant decrease was seen in
      intracellular GSH levels in C3H10T1/2 cells cultured with Glu, whereas the
      cellular proliferation activity was drastically decreased by the addition of the
      GSH depleter cyclohexene-1-one and the GSH biosynthesis inhibitor L-buthionine
      [S,R]-sulfoximine, respectively. Transient overexpression of both xCT and 4F2hc
      subunits led to an increased basal proliferative activity in C3H10T1/2 cells.
      These results suggest that Glu could suppress the cellular proliferation toward
      self-renewal through a mechanism associated with the depletion of intracellular
      GSH after promoting the retrograde operation of the cystine/Glu antiporter in
      C3H10T1/2 cells.

PMID- 17520697
TI  - Morphogenetic signals from chondrocytes promote chondrogenic and osteogenic
      differentiation of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are potentially useful cells for musculoskeletal
      tissue engineering. However, controlling MSC differentiation and tissue formation
      in vivo remains a challenge. There is a significant need for well-defined and
      efficient protocols for directing MSC behaviors in vivo. We hypothesize that
      morphogenetic signals from chondrocytes may regulate MSC differentiation. In
      micromass culture of MSCs, incubation with chondrocyte-conditioned medium (CCM)
      significantly enhanced the production of cartilage specific matrix including type
      II collagen. In addition, incubation of MSCs with conditioned medium supplemented
      with osteogenic factors induced more osteogenesis and accumulation of calcium and
      increased ALP activity. These findings reveal that chondrocyte-secreted factors
      promote chondrogenesis as well as osteogenesis of MSCs during in vitro micromass
      culture. Moreover, when MSCs expanded with chondrocyte-conditioned medium were
      encapsulated in hydrogels and subsequently implanted into athymic mice,
      basophilic extracellular matrix deposition characteristic of neocartilage was
      evident. These results indicate that articular chondrocytes produce suitable
      morphogenetic factors that induce the differentiation program of MSCs in vitro
      and in vivo.

PMID- 17520698
TI  - IGF-1 activates hEAG K(+) channels through an Akt-dependent signaling pathway in
      breast cancer cells: role in cell proliferation.
AB  - Previous work from our laboratory has shown that human ether a go-go (hEAG) K(+)
      channels are crucial for breast cancer cell proliferation and cell cycle
      progression. In this study, we investigated the regulation of hEAG channels by an
      insulin-like growth factor-1 (IGF-1), which is known to stimulate cell
      proliferation. Acute applications of IGF-1 increased K(+) current-density and
      hyperpolarized MCF-7 cells. The effects of IGF-1 were inhibited by hEAG
      inhibitors. Moreover, IGF-1 increased mRNA expression of hEAG in a time-dependent
      manner in parallel with an enhancement of cell proliferation. The MCF-7 cell
      proliferation induced by IGF-1 is inhibited pharmacologically by Astemizole or
      Quinidine or more specifically using siRNA against hEAG channel. Either mitogen
      activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K) are known
      to mediate IGF-1 cell proliferative signals through the activation of
      extracellular signal-regulated kinase 1/2 (Erk 1/2) and Akt, respectively. In MCF
      7 cells, IGF-1 rapidly stimulated Akt phosphorylation, whereas IGF-1 had little
      stimulating effect on Erk 1/2 which seems to be constitutively activated. The
      application of wortmannin was found to block the effects of IGF-1 on K(+)
      current. Moreover, the inhibition of Akt phosphorylation by the application of
      wortmannin or by a specific reduction of Akt kinase activity reduced the hEAG
      mRNA levels. Taken together, our results show, for the first time, that IGF-1
      increases both the activity and the expression of hEAG channels through an Akt
      dependent pathway. Since a hEAG channel is necessary for cell proliferation, its
      regulation by IGF-1 may thus play an important role in IGF-1 signaling to promote
      a mitogenic effect in breast cancer cells.

PMID- 17520699
TI  - Importance of several cysteine residues for the chloride conductance of trout
      anion exchanger 1 (tAE1).
AB  - In this study, we devised a cysteine-focused point mutation analysis of the
      chloride channel function of trout anion exchanger 1 (tAE1) expressed in X.
      laevis oocytes. Seven cysteines, belonging to the transmembrane domain of tAE1,
      were mutated into serines (either individually or in groups) and the effects of
      these mutations on the chloride conductance of injected oocytes were measured. We
      showed that three cysteines were essential for the functional expression of tAE1.
      Namely, mutations C462S, C583S and C588S reduced Cl(-) conductance by 68%, 52%
      and 83%, respectively, when compared to wild type tAE1. These residual
      conductances were still inhibited by 0.5 mM niflumic acid. Western blot
      experiments demonstrated that C462 was involved in protein expression onto the
      plasma membrane. A mutant devoid of this residue was unable to express onto the
      plasma membrane, especially if several other cysteines were missing:
      consequently, the cysteine-less mutant of tAE1 was not functional. C583 and C588
      were involved in the channel function of tAE1 as shown by anion substitution
      experiments proving that selectivity of the mutated pore differs from the wild
      type one. On the contrary, they were not involved in the Cl(-)/HCO(3)(-) exchange
      function of tAE1, as demonstrated by intracellular pH measurements. These and
      several complementary mutations allow us to conclude that a mutant of tAE1
      containing the sole C462 can drive a marginal Cl(-) current; however, the minimal
      configuration necessary to get optimal functional expression of the tAE1 chloride
      channel is that of a mutant containing unaffected residues C462, C583 and C588.

PMID- 17520700
TI  - Effect of hyperthermia and chemotherapeutic agents on TRAIL-induced cell death in
      human colon cancer cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      cancer therapeutic agent because of its tumor selectivity. TRAIL is known to
      induce apoptosis in cancer cells but spare most normal cells. In the previous
      study [Yoo and Lee, 2007], we have reported that hyperthermia could enhance the
      cytotoxicity of TRAIL-induced apoptosis. We observed in human colorectal cancer
      cell line CX-1 that TRAIL-induced apoptotic death and also that mild hyperthermia
      promoted TRAIL-induced apoptotic death through caspase activation and cytochrome
      c release. Although its effects in vivo are not clear, hyperthermia has been used
      as an adjunctive therapy for cancer. Hyperthermia is often accompanied by
      chemotherapy to enhance its effect. In this study, CX-1 colorectal adenocarcinoma
      cells were treated with TRAIL concurrently with hyperthermia and oxaliplatin or
      melphalan. To evaluate the cell death effects on tumor cells via hyperthermia and
      TRAIL and chemotherapeutic agents, FACS analysis, DNA fragmentation, and
      immunoblottings for PARP-1 and several caspases and antiapoptotic proteins were
      performed. Activities of casapse-8, caspase-9, and caspase-3 were also measured
      in hyperthermic condition. Interestingly, when analyzed with Western blot, we
      detected little change in the intracellular levels of proteins related to
      apoptosis. Clonogenic assay shows, however, that chemotherapeutic agents will
      trigger cancer cell death, either apoptotic or non-apoptotic, more efficiently.
      We demonstrate here that CX-1 cells exposed to 42 degrees C and chemotherapeutic
      agents were sensitized and died by apoptotic and non-apoptotic cell death even in
      low concentration (10 ng/ml) of TRAIL.

PMID- 17520701
TI  - Escaping the mouse trap: the selection of new Evo-Devo model species.
AB  - Among the many, sometimes contradictory, criteria that have been used for
      promoting model species, the most prominent has probably been their relevance for
      understanding human biology. Recently however, the debate has partly shifted from
      the search for evolutionary conservation (medicine-driven models) to a better
      understanding of the generative mechanisms underlying biological diversity (Evo
      Devo-driven models). Integration of multiple disciplines, beyond developmental
      genetics and evolutionary molecular genetics, as well as of innovative
      technologies will help biologists to open the massive realm of living species to
      genome manipulation and phenotypic investigation. However, a consensual list of
      model species must still be reached for optimizing the interplay between in
      silico analyses and in vivo experiments, and we claim that the Evo-Devo community
      should play a more energetic role in this endeavor. We discuss here a few
      criteria and limitations of major relevance to the choice of model species for
      Evo-Devo studies, and promote the use of a pragmatic approach. Finally, given the
      difficulties related to manipulating and breeding model species, we suggest the
      development of Evo-Devo virtual zoos maintaining breeding colonies of a selected
      set of species and from which eggs or staged embryos are available on order.

PMID- 17520702
TI  - Re: the feasibility of gene expression profiling generated in fine-needle
      aspiration specimens from patients with follicular lymphoma and diffuse large B
      cell lymphoma.

PMID- 17520703
TI  - Insights into spawning behavior and development of the European amphioxus
      (Branchiostoma lanceolatum).
AB  - The cephalochordate amphioxus (Branchiostoma sp.) is an important animal model
      for studying the evolution of chordate developmental mechanisms. Obtaining
      amphioxus embryos is a key step for these studies. It has been shown that an
      increase of 3-4 degrees C in water temperature triggers spawning of the European
      amphioxus (Branchiostoma lanceolatum) in captivity, however, very little is known
      about the natural spawning behavior of this species in the field. In this work,
      we have followed the spawning behavior of the European amphioxus during two
      spawning seasons (2004 and 2005), both in the field and in captivity. We show
      that animals in the field spawn approximately from mid-May through early July,
      but depending on the year, they show different patterns of spawning. Thus, even
      if temperature has a critical role in the induction of the spawning in captivity,
      it is not the major factor in the field. Moreover, we report some improvements on
      the methodology for inducing spawning in captivity (e.g. in maintenance, light
      cycle control and induction of spawning in a laboratory without running sea water
      system). These studies have important implications for amphioxus animal husbandry
      and for improving laboratory techniques to develop amphioxus as an experimental
      animal model.

PMID- 17520704
TI  - Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of
      the thyroid: a meta-analysis.
AB  - BACKGROUND: Numerous studies have investigated the clinical significance of BRAF
      mutation in papillary thyroid carcinoma (PTC). However, there have been
      conflicting data on the usefulness of BRAF mutation as a prognostic marker of
      PTC. To address this controversy, the frequency of the BRAF mutation and the
      associations between BRAF mutation and clinicopathologic parameters in PTC were
      evaluated by meta-analysis. METHODS: The relevant published studies were reviewed
      according to the defined selection criteria. The effect sizes of outcome
      parameters were estimated by odds ratio or weighted mean difference. RESULTS: The
      current meta-analysis included 12 studies with a total of 1168 patients. The
      frequency of the BRAF mutation was 49%. The BRAF mutation was associated with
      histologic subtype, the presence of extrathyroidal extension, and higher clinical
      stage, but not with age, sex, race, or tumor size. CONCLUSIONS: The effect of the
      BRAF mutation on the poor prognosis of PTC patients was evident from the current
      meta-analysis. The detection of the BRAF mutation may be used as an important
      prognostic marker of patients with PTC.

PMID- 17520705
TI  - Timing of biochemical failure and distant metastatic disease for low-,
      intermediate-, and high-risk prostate cancer after radiotherapy.
AB  - BACKGROUND: The relation of prostate cancer risk-group stratification and the
      timing of biochemical failure (BF) and distant metastasis (DM) is not well
      defined. The authors hypothesized that early failures due to subclinical
      micrometastasis at presentation could be differentiated from late failures due to
      local persistence. METHODS: A total of 1833 men with clinically localized
      prostate cancer treated with 3D-conformal radiotherapy with or without short-term
      androgen deprivation were retrospectively analyzed. By using American Society for
      Therapeutic Radiology and Oncology (ASTRO) and Phoenix (Nadir+2) definitions
      (developed at the ASTRO-RTOG [Radiation Therapy Oncology Group] consensus
      meeting, Phoenix, Arizona, January 21, 2005), the interval hazard rates of BF and
      DM were determined for men with low-risk, intermediate-risk, and high-risk
      disease. RESULTS: Median follow-up was 67 months. Multivariate analysis showed
      that increasing risk group was independently associated with higher ASTRO BF (P <
      .0001) and Nadir+2 BF (P < .0001). The preponderance (87%) of ASTRO BF occurred
      <or=4 years after radiotherapy, whereas Nadir+2 BF was more evenly spread over
      Years 1-12, with 43% at >4 years. The hazard of Nadir+2 BF persisted in Years 8
      12 in all risk groups. The interval hazard function for DM appeared to be
      biphasic (early peak followed by a drop and late increase) for intermediate-risk
      and high-risk patients, but no distinct early wave was evident for low-risk
      patients. CONCLUSIONS: Because of backdating, ASTRO BF underestimates late BF.
      Local persistence of disease is suggested by delayed Nadir+2 BF and subsequent
      late DM in every risk group. The paucity of early DM among those with low-risk
      tumors supports the hypothesis that occult micrometastases contributed to the
      early wave.

PMID- 17520709
TI  - Trends in stomach and pancreatic cancer incidence and mortality in England and
      Wales, 1951-2000.
AB  - BACKGROUND: The aim of this study was to describe period and cohort effects in
      incidence and mortality of stomach and pancreatic cancer in England and Wales.
      METHODS: National figures for mortality (1951-2000) and incidence (1971-2000)
      were analysed using log-linear Poisson regression models to obtain relative risks
      (RR) for period (year of incidence or death) and cohort (year of birth). RESULTS:
      Stomach cancer shows a pronounced cohort effect in mortality with a decline in RR
      in men from 2.20 (1876) to 0.47 (1946) and a reduction from 2.79 to 0.41 for
      women. Mortality to incidence ratios are now less than 0.70. Pancreatic cancer
      mortality (men) RR rose from 0.91 (1951-1955) to a peak 1.11 (1976-1980) and then
      declined to 0.90 (1996-2000). Women showed a similar pattern. Cohort RR (men)
      increased to a peak of 1.14 in 1916 and declined to 1.01 in 1946, and continued
      to fall; the peak occurred slightly later in women. Mortality to incidence ratios
      were near 1 in the first 20 years, declining to 0.95 in the last 10 years.
      CONCLUSION: Stomach cancer incidence has fallen continuously from 19(th) century
      birth cohorts onwards. Incidence of pancreatic cancer has fallen in successive
      birth cohorts after 1920; peak period risk was 1976-1990. Age-standardized
      mortality and case mortality for pancreatic cancer are declining.

PMID- 17520710
TI  - Long-term outcome of a multicentre randomized clinical trial of stapled
      haemorrhoidopexy versus Milligan-Morgan haemorrhoidectomy.
AB  - INTRODUCTION: Stapled haemorrhoidopexy is less painful than Milligan-Morgan
      haemorrhoidectomy, allowing an earlier return to working activities, but its long
      term efficacy is not fully established. This study reports the long-term follow
      up of a randomized clinical trial comparing the two techniques in 100 patients
      affected by third- and fourth-degree haemorrhoids. METHODS: All patients were
      contacted and invited to attend the clinic to assess long-term functional
      outcome. The degree of continence and satisfaction were assessed by
      questionnaire. Anal manometry and anoscopy were performed. RESULTS: Eighty
      patients were available after a median follow-up of 87 months. No statistically
      significant differences were found between the two groups in terms of
      incontinence, stenosis, pain, bleeding, residual skin tags or recurrent prolapse.
      A tendency towards a higher recurrence rate was reported in patients with fourth
      degree haemorrhoids, irrespective of the technique used. No significant changes
      in anal manometric values were found after surgery in either group. CONCLUSION:
      Both techniques are effective in the long term.

PMID- 17520711
TI  - Evaluation of various POSSUM models for predicting mortality in patients
      undergoing elective oesophagectomy for carcinoma.
AB  - BACKGROUND: The aim of the study was to validate the use of the Physiological and
      Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM),
      Portsmouth (P) POSSUM and upper gastrointestinal (O) POSSUM models in patients
      undergoing elective thoracic oesophagectomy for carcinoma. METHODS: The observed
      in-hospital mortality rates in 545 patients undergoing elective thoracic
      oesophagectomy for squamous cell carcinoma of the oesophagus in all public
      hospitals in Hong Kong was compared with rates predicted by POSSUM, P-POSSUM and
      O-POSSUM. The discriminatory power of these models was assessed using receiver
      operator characteristic (ROC) curve analysis. RESULTS: The observed mortality
      rate was 5.5 per cent, whereas rates predicted by POSSUM, P-POSSUM and O-POSSUM
      were 15.0, 4.7 and 10.9 per cent respectively. P-POSSUM showed no lack of fit (P
      = 0.814), but POSSUM (P < 0.001) and O-POSSUM (P = 0.002) showed lack of fit
      against observed mortality. POSSUM overpredicted mortality across nearly all risk
      groups, whereas O-POSSUM overpredicted mortality in patients with low
      physiological scores and in older patients. POSSUM (area under ROC curve 0.776)
      and P-POSSUM (0.776) showed equally good discriminatory power but O-POSSUM
      (0.676) was inferior. CONCLUSION: P-POSSUM provided the most accurate prediction
      of in-hospital mortality in this group of patients who had elective
      oesophagectomy.

PMID- 17520712
TI  - Nationwide study of the outcome of popliteal artery aneurysms treated surgically.
AB  - BACKGROUND: The aim was to study the epidemiology and outcomes of popliteal
      artery aneurysm (PA) treated surgically. METHODS: Among 110,000 procedures
      registered prospectively in the Swedish Vascular Registry (Swedvasc), there were
      717 primary operations for PA among 571 patients. Patient records were reviewed
      and data validated against other registries. RESULTS: The median age of the
      patients was 71 years; 5.8 per cent were women. Among 264 legs treated urgently,
      235 had acute ischemia and 24 had rupture. Of patients with unilateral PA, 28.1
      per cent had an aortic aneurysm, 8.4 per cent an iliac aneurysm and 9.4 per cent
      a femoral aneurysm. Extra-popliteal aneurysms were more common when the PAs were
      bilateral (P = 0.004). The rate of limb loss within 1 year of operation was 8.8
      per cent; 12.0 per cent for symptomatic and 1.8 per cent for asymptomatic limbs
      (P < 0.001). Risk factors for amputation were symptomatic disease, poor run-off,
      urgent treatment, age over 70 years, prosthetic graft and no preoperative
      thrombolysis when the ischaemia was acute. Amputation rates decreased over time
      (P = 0.003). Crude survival was 91.4 per cent at 1 year and 70.0 per cent at 5
      years. CONCLUSION: Multiple aneurysm disease was common when PAs were bilateral.
      Preoperative thrombolysis of acute thrombosis and the use of vein grafts for
      bypass improved outcome.

PMID- 17520713
TI  - Comparison of biphasic and reordered fat suppression for dynamic breast MRI.
AB  - PURPOSE: To optimize a reordered k-space acquisition that applies intermittent
      fat saturation (FS) pulses to allow for a time-efficient reduction of fat signal
      in breast MR images, and compare it with an elliptic-centric biphasic FS method
      in terms of the degree of fat suppression and speed. MATERIALS AND METHODS: The
      behavior of the fat and water signals under the influence of the reordered
      sequence was characterized. This allowed us to optimize the flip angle and
      visualize the expected artifacts by deriving the point spread function (PSF) of
      the fat signal. We compared the two sequences by acquiring images with a varying
      number of FS pulses, with a corresponding difference in scan time. The quality of
      the images was assessed by comparison with images obtained with full fat
      suppression as measured by a root-mean-square (RMS) error metric. RESULTS: The
      reordered sequence allowed for an approximately twofold reduction in error
      compared to the biphasic sequence for the same scan time. With the reordered
      sequence and optimized scan parameters, we were able to reduce the time spent on
      fat suppression by as much as 99% with no discernible reduction in image quality.
      CONCLUSION: This method will allow robust fat suppression with virtually no
      extension in imaging time for dynamic contrast-enhanced (DCE)-MRI.

PMID- 17520716
TI  - Fluid-induced wall shear stress in anthropomorphic brain aneurysm models: MR
      phase-contrast study at 3 T.
AB  - PURPOSE: To study spatial and temporal distribution of wall shear stress (WSS) of
      intracranial aneurysm models using magnetic resonance phase contrast (MR-PC)
      imaging, and to compare results to those obtained in our previous study using
      laser Doppler velocimetry (LDV). MATERIALS AND METHODS: High-resolution MR-PC
      imaging was performed on aneurysm models created from 3D in vivo data of a
      basilar artery (BA) tip and a middle cerebral artery (MCA) aneurysm. WSS was
      measured by calculating the rate of shearing strain using image postprocessing
      techniques. WSS was characterized using several parameters, including average WSS
      and oscillatory shear index (OSI). RESULTS: Both aneurysms showed the highest WSS
      at an ostium. A bleb region in the BA tip and a dome region in the MCA aneurysm
      were consistently exposed to high WSS within a small local area with high spatial
      variation and little temporal change in comparison to other aneurysmal regions.
      High correlation was noted for the spatial distribution at the peak systole
      between the MR-PC and the LDV studies, with the correlation coefficient value of
      77% to 81%. CONCLUSION: MR-PC imaging showed good agreement with the reference
      LDV study, confirming its potential to study hemodynamics of physiologically
      realistic in vitro intracranial aneurysm models. Characteristic patterns of WSS,
      such as high spatial variation and absence of temporal variation, combined with
      locally increased high WSS as determined by MR-PC imaging, may elucidate the
      effect of WSS on aneurysmal development and rupture.

PMID- 17520715
TI  - High cerebral blood volume in human gliomas predicts deletion of chromosome 1p:
      Preliminary results of molecular studies in gliomas with elevated perfusion.
AB  - PURPOSE: To determine if increased perfusion using dynamic susceptibility
      contrast perfusion MRI (DSC MRI) in gliomas may be predictive of 1p19q deletions.
      Loss of heterozygosity of chromosomes 1p and 19q confers responsiveness to
      chemotherapy improving survival in gliomas. MATERIALS AND METHODS: We
      retrospectively reviewed 16 patients who had DSC MRI and molecular studies of
      their excised gliomas for 1p19q deletions. Allelic status was assessed by loss of
      heterozygosity using polymerase chain reaction (PCR). DNA was extracted from
      paraffin curls of brain tumor sections and nail clippings. Relative cerebral
      blood volume (rCBV) measurements were then statistically compared with the
      presence of 1p and 19q deletions. RESULTS: Patients with 1p19q deletions (N = 7)
      demonstrated rCBV values of 10.54 +/- 2.93. Patients without 1p deletions (N = 9)
      had rCBV values of 4.84 +/- 2.4 (P = 0.012). Logistic regression demonstrated
      that rCBV was able to predict the presence of a 1p deletion to significance
      levels of 0.038 and 0.044, adjusted and not adjusted for age and sex,
      respectively. The kappa coefficient for the agreement between predicted deletion
      status using rCBV and the truedeletion status was 0.746 (P = 0.0028). Deletions
      of 19q alone, or together with 1p deletions, were not associated with high rCBV.
      CONCLUSION: Histopathologic, molecular, and imaging evidence supports increased
      neovascularity in gliomas with 1p deletions in this preliminary study. We propose
      a diagnostic algorithm to obtain molecular studies in gliomas demonstrating high
      rCBV.

PMID- 17520717
TI  - Magnetic resonance imaging to assess acute changes in atrial and ventricular
      parameters after transcatheter closure of atrial septal defects.
AB  - PURPOSE: To evaluate acute changes in atrial and ventricular parameters by the
      use of cardiac magnetic resonance imaging (MRI) in patients with percutaneous
      transcatheter atrial septal defects (ASD) closure. MATERIALS AND METHODS: The
      study included 14 patients (six males and eight females, 45 +/- 18 years) with
      congenital ASD. Cardiac MRI (1.5T Philips Intera CV) was performed before and
      within 24 hours after transcatheter ASD closure. Right atrial (RA) and left
      atrial (LA) dimensions, as well as right (RV) and left (LV) ventricular end
      diastolic (ED) volumes were determined. Atrial size was assessed by planimetry of
      the maximum RA and LA areas in a standard four-chamber view, and ventricular
      volumes were calculated according to a modified Simpson's rule in short-axis
      views. RESULTS: The mean RA decreased significantly from 27.6 +/- 6.4 cm(2)
      before closure to 24.4 +/- 5.6 cm(2) after the procedure (P = 0.0018), whereas
      the LA area did not change (24.1 +/- 4.7 cm(2) vs. 23.8 +/- 5.2 cm(2), P = 0.76).
      The RV volumes, volume index, and ejection fraction (EF) decreased significantly
      from 229 +/- 64 mL to 181 +/- 43 mL (P < 0.001, average reduction = 19% +/- 15%),
      from 126.0 +/- 37.2 mL/m(2) to 96.6 +/- 28.6 mL/m(2) (P < 0.0001) and from 64 +/-
      5% to 58% +/- 7% (P = 0.01), respectively. The LV volumes and volume index
      remained unchanged (114 +/- 25 mL vs. 118 +/- 22 mL, P = 0.18, 63.5 +/- 13.5
      mL/m(2) vs. 63.0 +/- 17.4 mL/m(2), P = 0.83). Left-right shunting decreased from
      40% +/- 15% to 9% +/- 15% (P < 0.001). CONCLUSION: Cardiac MRI can reveal
      detailed information on acute changes in shunt fraction and ventricular
      dimensions after ASD closure. ASD closure by percutaneous transcatheter device
      implantation results within 24 hours in a significant reduction of shunt
      fraction, RA and RV sizes, and RV function, whereas LA and LV dimensions remain
      unchanged.

PMID- 17520718
TI  - Normalized left ventricular volumes and function in thalassemia major patients
      with normal myocardial iron.
AB  - PURPOSE: To determine the reference range in thalassemia major (TM) for left
      ventricular (LV) function. MATERIALS AND METHODS: We used cardiovascular magnetic
      resonance (CMR) to measure heart volumes and function in 81 TM patients with
      normal myocardial T2* measurements (T2* > 20 msec) and by inference without
      excess myocardial iron. Forty age- and gender-matched healthy controls were also
      studied. RESULTS: Resting LV volumes and function normalized to body surface area
      differed significantly between TM patients and controls. The lower limit and the
      mean for ejection fraction (EF) were higher in TM patients (males 59 vs. 55%,
      mean 71% vs. 65%; females 63 vs. 59%, mean 71% vs. 67%; both P < 0.001). The
      upper limit and mean for end-diastolic volume index were higher in TM patients
      (males 152 vs. 105 mL/m(2), mean 97 vs. 84 mL/m(2); females 121 vs. 99 mL/m(2),
      mean 87 vs. 79 mL/m(2); both P < 0.05). In TM patients the cardiac index (P <
      0.001) was increased. CONCLUSION: At rest, TM patients with a normal myocardial
      T2* have different "normal" values for LV volume and function parameters compared
      to controls, and this has the potential to lead to a misdiagnosis of
      cardiomyopathy. We present new reference "normal" ranges in TM to alleviate this
      problem.

PMID- 17520719
TI  - Clinical aspects of the apparent diffusion coefficient in 3He MRI: results in
      healthy volunteers and patients after lung transplantation.
AB  - PURPOSE: To measure the apparent diffusion coefficient (ADC) after inhalation of
      hyperpolarized (3)He in healthy volunteers and lung transplant recipients, and
      demonstrate the gravity dependence of ADC values. MATERIALS AND METHODS: Six
      healthy volunteers, 10 patients after single-lung transplantation, and six
      patients after double-lung transplantation were examined at 1.5T during
      inspiration and expiration. The inhalation of 300 mL of hyperpolarized (3)He was
      performed with a computer-controlled delivery device. A two-dimensional fast low
      angle shot (FLASH) sequence measured the (3)He diffusive gas movement. From these
      data the ADC was calculated. RESULTS: The mean ADC was 0.143 cm(2)/second in
      healthy individuals, 0.162 cm(2)/second in transplanted healthy lungs, and 0.173
      cm(2)/second in rejected transplanted lungs, whereas it was 0.216 cm(2)/second in
      native fibrotic lungs and 0.239 cm(2)/second in emphysematous lungs. The
      difference in mean ADC values among healthy lungs, healthy transplanted lungs,
      and native diseased lungs was significant (P < 0.001). In inspiration the healthy
      volunteers showed higher ADC values in the anterior than in the posterior parts
      of the lungs. In expiration this gradient doubled. CONCLUSION: An anterior
      posterior (A/P) gradient was found in inspiration and expiration in healthy
      lungs. Healthy, transplanted, and native diseased lungs had significantly
      different mean ADC values. From our preliminary results, (3)He MRI appears to be
      sensitive for detecting areas of abnormal ventilation in transplanted lungs.

PMID- 17520720
TI  - Quantification of perfusion and permeability in breast tumors with a
      deconvolution-based analysis of second-bolus T1-DCE data.
AB  - PURPOSE: To test the feasibility of using a second-bolus injection, added to a
      routine breast MRI examination, to measure regional perfusion and permeability in
      human breast tumors. MATERIALS AND METHODS: In 30 patients with breast tumors,
      first a routine whole-breast T1-DCE sequence was applied, and the slice where the
      lesion enhanced maximally was located. At that slice position, T1-weighted MR
      images were acquired at 0.3-second resolution using a second-bolus dynamic
      inversion recovery (IR)-prepared turbo field echo (TFE) sequence. A pixel-by
      pixel model-independent deconvolution of the relative signal enhancement was
      performed to estimate the tumor blood flow (TBF), tumor volume of distribution
      (TVD), mean transit time (MTT), extraction flow product (EF), and extraction
      fraction (E). In addition to this pilot study, a first appraisal of its
      sensitivity to tissue type was made on the basis of a small patient cohort.
      RESULTS: In the malignant tumors, the parametric maps clearly delineated tumors
      from the breast tissue and enabled visualization of the heterogeneity. The
      deconvolution analysis provided objective parametric maps of tumor perfusion with
      a mean TBF (84 +/- 48 mL/100 mL/minute) in malignant tumors in the high range of
      literature values. CONCLUSION: In terms of these perfusion values, our method
      appears promising to quantitatively characterize tumor pathophysiology. However,
      the number of patients was limited, and the separation between malignant and
      benign groups was not clear-cut. Additional parameters generated through
      compartment modeling may improve the tumor differentiation.

PMID- 17520721
TI  - Insight into RF power requirements and B1 field homogeneity for human MRI via
      rigorous FDTD approach.
AB  - PURPOSE: To study the dependence of radiofrequency (RF) power deposition on B(0)
      field strength for different loads and excitation mechanisms. MATERIAL AND
      METHODS: Studies were performed utilizing a finite difference time domain (FDTD)
      model that treats the transmit array and the load as a single system. Since it
      was possible to achieve homogenous excitations across the human head model by
      varying the amplitudes/phases of the voltages driving the transmit array, studies
      of the RF power/B(0) field strength (frequency) dependence were achievable under
      well-defined/fixed/homogenous RF excitation. RESULTS: Analysis illustrating the
      regime in which the RF power is dependent on the square of the operating
      frequency is presented. Detailed studies focusing on the RF power requirements as
      a function of number of excitation ports, driving mechanism, and
      orientations/positioning within the load are presented. CONCLUSION: With variable
      phase/amplitude excitation, as a function of frequency, the peak-then-decrease
      relation observed in the upper axial slices of brain with quadrature excitation
      becomes more evident in the lower slices as well. Additionally, homogeneity
      optimization targeted at minimizing the ratio of maximum/minimum B(1) (+) field
      intensity within the region of interest, typically results in increased RF power
      requirements (standard deviation was not considered in this study). Increasing
      the number of excitation ports, however, can result in significant RF power
      reduction.

PMID- 17520722
TI  - Misregistration artifacts in image-derived arterial input function in non-echo
      planar imaging-based dynamic contrast-enhanced MRI.
AB  - PURPOSE: To characterize misregistration artifact in arterial input function
      (AIF) pixels in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
      using a two-dimensional non-echo-planar imaging (EPI)-based gradient-recalled
      echo (GRE) sequence. MATERIALS AND METHODS: Dynamic gadopentetate-enhanced MRI
      was acquired in the rat using a semikeyhole acquisition scheme. The AIF was
      obtained from abdominal aorta pixels. Different sliding-window reconstruction
      techniques were applied to determine which lines in a series of the semikeyhole
      acquisition were associated with the misregistration artifacts. RESULTS: The
      misregistration along the phase-encoding direction arose when k-space lines were
      acquired during the rise-time of the aortic gadolinium concentration. The maximum
      blood concentration of gadolinium estimated from the phase shift calculation
      agreed with that estimated from dosage. CONCLUSION: AIF misregistration results
      from a phase shift due to increasing gadolinium concentration in the aorta, and
      may need to be considered in small animal DCE-MRI studies with a high rate of
      rise in the AIF in high-field MR applications.

PMID- 17520723
TI  - Rapid dark-blood carotid vessel-wall imaging with random bipolar gradients in a
      radial SSFP acquisition.
AB  - PURPOSE: To investigate and evaluate a new rapid dark-blood vessel-wall imaging
      method using random bipolar gradients with a radial steady-state free precession
      (SSFP) acquisition in carotid applications. MATERIALS AND METHODS: The carotid
      artery bifurcations of four asymptomatic volunteers (28-37 years old, mean age =
      31 years) were included in this study. Dark-blood contrast was achieved through
      the use of random bipolar gradients applied prior to the signal acquisition of
      each radial projection in a balanced SSFP acquisition. The resulting phase
      variation for moving spins established significant destructive interference in
      the low-frequency region of k-space. This phase variation resulted in a net
      nulling of the signal from flowing spins, while the bipolar gradients had a
      minimal effect on the static spins. The net effect was that the regular SSFP
      signal amplitude (SA) in stationary tissues was preserved while dark-blood
      contrast was achieved for moving spins. In this implementation, application of
      the random bipolar gradient pulses along all three spatial directions nulled the
      signal from both in-plane and through-plane flow in phantom and in vivo studies.
      RESULTS: In vivo imaging trials confirmed that dark-blood contrast can be
      achieved with the radial random bipolar SSFP method, thereby substantially
      reversing the vessel-to-lumen contrast-to-noise ratio (CNR) of a conventional
      rectilinear SSFP "bright-blood" acquisition from bright blood to dark blood with
      only a modest increase in TR (approximately 4 msec) to accommodate the additional
      bipolar gradients. CONCLUSION: Overall, this sequence offers a simple and
      effective dark-blood contrast mechanism for high-SNR SSFP acquisitions in vessel
      wall imaging within a short acquisition time.

PMID- 17520724
TI  - Correction of temporal misregistration artifacts in jet flow by conventional
      phase-contrast MRI.
AB  - PURPOSE: To show that accuracy of jet flow representation by magnetic resonance
      (MR) phase-contrast (PC) velocity-encoded (VE) cine imaging is dominated by error
      terms resulting from the temporal distribution of data, and to present a
      generally applicable data interpolation-based approach to correct for this
      phenomenon. MATERIALS AND METHODS: Phase-contrast data were acquired in a
      stenotic orifice flow phantom using a physiologic pulsatile flow waveform. A
      temporally registered scan, acquired without data segmentation or interleaving
      was obtained (17 minutes) and taken as the reference (REF). Conventional PC data
      sets were acquired using segmentation and data interleaving. An enhanced temporal
      registration (ETR) algorithm was applied to the acquired data to temporally
      interpolate component sets and output data at matching time points, thereby
      reducing temporal dispersion. RESULTS: Compared to the REF data, conventionally
      processed PC data consistently overestimated peak velocities in laminar jet flow
      regions (127% +/- 28%) and exhibited relatively weak correlations (r = 0.67 +/-
      0.23). The ETR-processed data better represented peak velocities (101% +/- 13%, P
      < 0.001) and correlated more closely with the REF data (r = 0.94 +/- 0.05, P <
      0.001). CONCLUSION: The temporal distribution of PC data impacts the accuracy of
      velocity representation in pulsatile jet flow. A temporal registration
      postprocessing algorithm can minimize loss of accuracy.

PMID- 17520725
TI  - High temporal resolution breathheld 3D FIESTA CINE imaging: validation of
      ventricular function in patients with chronic myocardial infarction.
AB  - PURPOSE: To develop a gated single-breathhold, high temporal resolution three
      dimensional (3D) CINE imaging technique and to evaluate its accuracy in
      volumetric and functional quantification in patients with chronic myocardial
      infarction. MATERIALS AND METHODS: A 3D CINE steady-state free precession (SSFP)
      pulse sequence was developed incorporating variable temporal sampling of the low
      and high spatial frequency k-space data to reduce breathhold time and parallel
      imaging to increase temporal resolution. Reconstruction with retrospective
      interpolation enabled complete R-R interval coverage. Feasibility was assessed in
      eight patients with chronic myocardial infarction and ventricular functional
      values were compared to those of a 2D CINE acquisition. RESULTS: There was no
      significant difference between the 3D CINE and 2D CINE for end-diastolic volume
      (168 +/- 73 vs. 177 +/- 59 mL, respectively; P < 0.27), end-systolic volume (81
      +/- 62 vs. 79 +/- 53 mL; P < 0.81), and ejection fraction (EF) measurements (55
      +/- 14% vs. 58 +/- 14%; P < 0.14). The mean difference in EF was less than 2.5%.
      A wall motion assessment indicated a good agreement, with a weighted kappa value
      of 0.62. CONCLUSION: High temporal resolution 3D CINE SSFP imaging of the whole
      heart can be obtained in a single breathhold and yield ventricular function
      measurements similar to 2D CINE methods.

PMID- 17520726
TI  - Magnetic resonance cholangiography of biliary strictures after liver
      transplantation: a prospective double-blind study.
AB  - PURPOSE: To compare magnetic resonance cholangiography (MRC) with endoscopic
      retrograde cholangiography (ERC) in quantitatively evaluating biliary strictures
      in liver transplant recipients. MATERIALS AND METHODS: Eight liver transplant
      recipients with suspected biliary complications were referred for ERC and also
      underwent MRC within 24 hours using a combination of single-shot rapid
      acquisition with relaxation enhancement (SS-RARE) and three-dimensional (3D)-RARE
      sequences. The studies were independently interpreted by two blinded radiologists
      and a single blinded endoscopist who recorded the presence of a stricture and/or
      upstream dilatation, the ratio of recipient-to-donor duct diameters at the
      anastomosis, as well as the proximal duct diameter, length, and percent stenosis
      of any stricture detected. RESULTS: Using ERC as the standard of reference, MRC
      had a sensitivity and negative predictive value of 100%, mean specificity of
      83.3%, and mean positive predictive value of 92.9% in the detection of six
      strictures. Compared with ERC, MRC obtained accurate measurements of recipient-to
      donor duct diameter ratios (r, 0.91; P < 0.01), proximal duct diameters (r, 0.83,
      P < 0.05), stricture lengths (r, 0.58; P = 0.06), and percent stenosis (r, 0.78;
      P = 0.06). CONCLUSION: MRC can provide equivalent imaging to ERC and can reliably
      identify and quantitatively evaluate biliary strictures in post-orthotopic liver
      transplantation (OLT) patients.

PMID- 17520727
TI  - MRI detection of macrophages labeled using micrometer-sized iron oxide particles.
AB  - PURPOSE: To evaluate cellular labeling of immune cells using micron-sized iron
      oxide particles (MPIOs) and evaluate the MR relaxivity and MRI detection of the
      labeled cells. MATERIALS AND METHODS: Immune cells isolated from mice and rats
      were labeled with three different sizes of MPIO particles (0.35, 0.90, or 1.63
      microm). These labeled cells were characterized using transmission electron
      microscopy (TEM), fluorescence microscopy, flow cytometry, MR relaxometry, and
      MRI. RESULTS: Macrophage uptake of MPIOs was found to be highest for the 1.63
      microm size particles. MR relaxivity measurements indicated greater spin-spin
      relaxation for MPIO-labeled cells relative to cells labeled with nanometer-sized
      ultra-small superparamagnetic iron oxide (USPIO) particles with similar iron
      content. TEM and fluorescence microscopy indicated cellular uptake of multiple
      MPIO particles per cell. Macrophages labeled with 1.63-microm MPIOs had an
      average cellular iron uptake of 39.1 pg/cell, corresponding to approximately 35
      particles per cell. CONCLUSION: Cells labeled with one or more MPIO particles
      could be readily detected ex vivo at 11.7 Tesla and after infusion of the MPIO
      labeled macrophages into the kidney of a rat, hypointense regions of the outer
      cortex are observed, in vivo, by MRI at 4.7 Tesla.

PMID- 17520728
TI  - Quantitative evaluation of the relaxivity effects of iodine on GD-DTPA enhanced
      MR arthrography.
AB  - PURPOSE: To quantify the effect of iodine on the gadolinium (Gd) contrast
      enhanced signal in MR arthrography. MATERIALS AND METHODS: Saline solutions of Gd
      contrast agent (0-1 mmol/liter) were mixed with iodinated contrast agent (0-185
      mmol/liter). The T1 and T2 relaxation constants of these solutions were measured
      at 1.5T. Different types of commonly used iodinated contrast agents as well as
      sodium iodide (NaI) solutions were also analyzed. RESULTS: Iodine caused
      significant T2 shortening and some T1 shortening in Gd contrast solutions. Both
      contrast agents independently obeyed the standard relaxation relation, and their
      mixture obeyed a modified version of this relation. The side chains in various
      iodine molecules and their viscosities affected the relaxation properties
      differently. For various spin-echo (SE) sequences, the signal from synovial fluid
      containing different concentrations of the two contrast agents was calculated.
      The T2-weighted signal appeared to be most affected by the increase in iodine
      concentrations. In the absence of Gd contrast, all SE sequences showed an initial
      increase in signal from iodine contrast. CONCLUSION: A generalized relation for
      the relaxivities of Gd contrast in the presence of iodine was established. The
      side chains of iodine contrast were found to alter the relaxivities of Gd
      contrast. Imaging with proton density (PD)-weighted SE with only iodine contrast
      agent was found to be feasible.

PMID- 17520729
TI  - High-speed 3T MR spectroscopic imaging of prostate with flyback echo-planar
      encoding.
AB  - Prostate MR spectroscopic imaging (MRSI) at 3T may provide two-fold higher
      spatial resolution over 1.5T, but this can result in longer acquisition times to
      cover the entire gland using conventional phase-encoding. In this study, flyback
      echo-planar readout trajectories were incorporated into a Malcolm Levitt's
      composite-pulse decoupling sequence (MLEV)-point-resolved spectroscopy sequence
      (PRESS) to accelerate the acquisition of large array (16 x 16 x 8), high spatial
      (0.154 cm(3)) resolution MRSI data by eight-fold to just 8.5 minutes. Artifact
      free, high-quality MRSI data was obtained in nine prostate cancer patients. Easy
      data reconstruction and the robustness of the flyback echo-planar encoding make
      this technique particularly suitable for the clinical setting. The short
      acquisition time provided by this method reduces the 3T prostate MRI/MRSI exam
      time, allows longer repetition times, and/or allows the acquisition of additional
      MR acquisitions within the same exam.

PMID- 17520730
TI  - Investigation of coil phase compensation in 3D imaging at very high acceleration
      factors.
AB  - PURPOSE: To investigate the confounding effect of the coil phase in highly
      accelerated parallel imaging with small coils, contextualize the effect in terms
      of single-echo acquisition (SEA) imaging, and show that it can be managed in the
      case of 3D imaging. MATERIALS AND METHODS: The effects of the coil phase
      variations in a 64-channel array of surface microcoils were modeled. Fully
      encoded 64 x 128 x 64 (N(phase enc) x N(readout) x N(slice enc)) 3D data sets
      were obtained, from which factor of 64 accelerated 3D image sets (1 x 128 x 64
      each) were extracted from single phase-encoding lines, each representing a
      different phase compensation value. RESULTS: A comparison of the SEA images
      indicates that the choice of a compromise value for phase compensation
      successfully enabled a straightforward extension of SEA imaging to three
      dimensions. The use of the single compromise compensation value in the 3D
      acquisition resulted in a signal-to-noise ratio (SNR) penalty ranging from 6% to
      41% through the slab when compared to the highest SNR possible using any phase
      compensation value. CONCLUSION: The coil-related phase shift issues inherent to
      highly accelerated imaging will require further study, but this work indicates
      the general nature of the problem and, more auspiciously, shows that it can be
      mitigated for at least this application.

PMID- 17520731
TI  - Functional MR imaging of the female pelvis.
AB  - Recent developments in MR techniques have magnified the roles and potential of
      MRI in the female pelvis. This article reviews the techniques and clinical
      applications of functional MRI (fMRI) of the female pelvis, including cine MRI,
      diffusion-weighted MRI (DWI), and dynamic contrast-enhanced (DCE)-MRI. Cine MRI
      is a useful tool for evaluating uterine contractility, including sustained
      contraction and peristalsis, in a variety of conditions and gynecologic
      disorders, and for evaluating pelvic-floor weakness. DWI can demonstrate abnormal
      signals in pathologic foci based on differences in molecular diffusion. It also
      enables the quantitative evaluation of the apparent diffusion coefficient (ADC),
      which may be useful for distinguishing malignant from benign tissues and
      monitoring therapeutic outcome. DCE-MRI has the potential to improve tumor
      detection and local staging, and can also provide quantitative information about
      perfusion of the tumor, which may be useful for both monitoring therapeutic
      effects and predicting therapeutic outcome. Understanding the roles played by
      functional MR techniques in the female pelvic region is beneficial not only for
      determining clinical applications, but also for developing further investigations
      with MRI.

PMID- 17520732
TI  - Soft-tissue tumors evaluated by line-scan diffusion-weighted imaging: influence
      of myxoid matrix on the apparent diffusion coefficient.
AB  - PURPOSE: To compare the apparent diffusion coefficients (ADCs) of myxoid and
      nonmyxoid soft-tissue tumors using line-scan diffusion-weighted imaging (LSDWI),
      and to investigate the myxoid matrix influence on ADCs of soft-tissue tumors.
      MATERIALS AND METHODS: This study enrolled 44 patients with soft tissue tumors.
      They were divided into two groups: one with myxoid-containing soft-tissue tumors
      (N = 23) and the other with nonmyxoid soft-tissue tumors (N = 21). The 44
      patients were also classified histologically into 26 with malignant soft-tissue
      tumors and 18 with benign soft-tissue tumors. LSDWI was performed using b values
      of 5 and 1000 second/mm(2). The ADCs of the tumors were calculated and compared
      for myxoid and nonmyxoid tumors and for benign and malignant tumors. RESULTS: The
      ADC (mean +/- SD) was 1.92 +/- 0.41 x 10(-3) mm(2)/second in myxoid containing
      tumors, whereas the ADC was 0.97 +/- 0.33 x 10(-3) mm(2)/second in nonmyxoid
      tumors. The ADCs of the myxoid and nonmyxoid tumors were significantly different
      (P < 0.01). The ADCs were 1.45 +/- 0.59 x 10(-3) mm(2)/second in malignant tumors
      and 1.50 +/- 0.64 x 10(-3) mm(2)/second in benign tumors. The ADCs of benign and
      malignant soft-tissue tumors were not significantly different. CONCLUSION: The
      ADCs of myxoid-containing soft-tissue tumors were significantly higher than those
      of nonmyxoid soft-tissue tumors. The myxoid matrix influences ADCs of both benign
      and malignant soft-tissue tumors.

PMID- 17520733
TI  - Contrast-to-noise ratio (CNR) as a quality parameter in fMRI.
AB  - PURPOSE: To evaluate the impact of data quality on the localization of brain
      activation in functional magnetic resonance imaging (fMRI) and to explore whether
      the temporal contrast-to-noise-ratio (CNR) provides a quantitative parameter to
      estimate fMRI quality. MATERIALS AND METHODS: We investigated two methods for
      defining the CNR by comparing them on a single-run, single session, as well as on
      a group-wise basis. The CNRs of healthy subjects and a group of patients with
      brain lesions were calculated using two different strategies: one based on a
      general linear model (GLM) analysis (CNR_SPM), and one that acts as an adaptive
      low-pass filter and assumes that the high-frequency components contain the
      temporal noise (CNR_SG). Runs with low CNR were identified as outliers using a
      common exclusion criterion (2 x standard deviation (SD)). RESULTS: The results of
      the two CNR methods are highly correlated. Both between and within subjects and
      patients the CNR showed quite large variations, but the average CNR did not
      differ between a group of healthy subjects and a patient group. In total, seven
      of 213 runs (3.3% of all runs) had to be excluded when CNR_SG was used, and 14 of
      213 (6.6%) runs had to be excluded when CNR_SPM was used. CONCLUSION: Calculating
      the CNR using an adaptive low-pass filter gives similar results to a GLM-based
      approach and could be advantageous for cases in which the hemodynamic response
      function (HRF) differs significantly from common assumptions. The CNR can be used
      to identify and exclude runs with suboptimal CNR, and to identify sessions with
      insufficient data quality. The CNR may serve as a quantitative and intuitive
      parameter to assess the performance and quality of clinical fMRI investigations,
      including information on both functional performance (contrast) and data quality
      (noise caused by the system and physiology).

PMID- 17520734
TI  - TSE with average-specific phase encoding ordering for motion detection and
      artifact suppression.
AB  - PURPOSE: To detect motion-corrupted measurements in multi-average turbo-spin-echo
      (TSE) acquisitions and reduce motion artifacts in reconstructed images. MATERIALS
      AND METHODS: An average-specific phase encoding (PE) ordering scheme was
      developed for multi-average TSE sequences in which each echo train is assigned a
      unique PE pattern for each pre-averaged image (PAI). A motion detection algorithm
      is developed based on this new PE ordering to identify which echo trains in which
      PAIs are motion-corrupted. The detected PE views are discarded and replaced by
      uncorrupted k-space data of the nearest PAI. Both phantom and human studies were
      performed to investigate the effectiveness of motion artifact reduction using the
      proposed method. RESULTS: Motion-corrupted echo trains were successfully detected
      in all phantom and human experiments. Significant motion artifact suppression has
      been achieved for most studies. The residual artifacts in the reconstructed
      images are mainly caused by residual inconsistencies that remain after the
      corrupted k-space data is corrected. CONCLUSION: The proposed method combines a
      novel data acquisition scheme, a robust motion detection algorithm, and a simple
      motion correction algorithm. It is effective in reducing motion artifacts for
      images corrupted by either bulk motion or local motion that occasionally happens
      during data acquisition.

PMID- 17520735
TI  - Cardiac amyloidosis: MR imaging findings and T1 quantification, comparison with
      control subjects.
AB  - In cardiac amyloidosis an interstitial deposition of amyloid fibrils causes
      concentric thickening of the atrial and ventricular walls. We describe the
      results of tissue characterization of the myocardium by T1 quantification and MRI
      findings in a patient with cardiac amyloidosis. The T1 time of the myocardium was
      elevated compared to that in individuals without amyloidosis. The T1 time of the
      myocardium was 1387 +/- 63 msec (mean value obtained from four measurements +/-
      standard deviation [SD]) in the patient with cardiac amyloidosis, while the
      reference value obtained from the myocardium of 10 individuals without known
      myocardial disease was 1083 +/- 33 msec (mean value +/- SD). In combination with
      other MR findings suggestive of amyloidosis, such as homogeneous thickening of
      the ventricular and atrial walls, thickening of the valve leaflets, restrictive
      filling pattern, and reduction of systolic function, T1 quantification may
      increase diagnostic confidence.

PMID- 17520736
TI  - Contrast-dose relation in first-pass myocardial MR perfusion imaging.
AB  - PURPOSE: To determine the regime of linear contrast enhancement in human first
      pass perfusion cardiovascular magnetic resonance (CMR) imaging to improve
      accuracy in myocardial perfusion quantification. MATERIALS AND METHODS: A total
      of 10 healthy subjects were studied on a clinical 1.5T MR scanner. Seven doses of
      Gd-DTPA ranging from 0.00125 to 0.1 mmol/kg of body weight (b.w.) were
      administered as equal volumes by rapid bolus injection (6 mL/second). Resting
      periods of 15 minutes were introduced after delivery of Gd doses >0.01 mmol/kg
      b.w. For each subject, two series of rest perfusion scans were performed using
      two different multislice saturation-recovery perfusion sequences. Maximum
      contrast enhancement and maximum upslope were obtained in the blood pool of the
      left ventricular (LV) cavity and in the myocardium. The range of linear contrast
      dose relation was determined by linear regression analysis. RESULTS: MR signal
      intensity increased linearly for contrast agent concentrations up to 0.01 mmol/kg
      b.w. in the LV blood pool and up to 0.05 mmol/kg b.w. in the myocardium. For Gd
      concentrations exceeding these thresholds the signal intensity response was not
      linear with respect to the contrast agent dose. CONCLUSION: Quantitative
      evaluation of cardiac MR perfusion data needs to account for signal saturation in
      both the LV blood pool and the myocardium.

PMID- 17520737
TI  - Three-dimensional gradient-echo imaging for percutaneous MR-guided laser therapy
      of liver metastasis.
AB  - PURPOSE: To evaluate the use of three-dimensional (3D) gradient-echo (GRE)
      magnetic resonance imaging (MRI) for percutaneous MR-guided catheter placement
      for laser therapy of liver metastases. MATERIALS AND METHODS: Thirty-four
      patients were included. A total of 122 MR-guided percutaneous punctures of 67
      liver metastases were performed on a 1.5T scanner (Symphony and Sonata; Siemens,
      Erlangen, Germany) using a 5.5F microcatheter system and titanium needle
      (Monocath; MeoMedical, Augsburg, Germany). In 88 of 122 procedures, a 2D fast low
      angle shot (FLASH) T1-weighted GRE breath-hold sequence was acquired in the axial
      plane and if necessary in a second plane. Sequences were acquired and reviewed
      using the panel in the control room. In 34 of 122 procedures a 3D FLASH T1
      weighted fat-saturated GRE (volume-interpolated breath-hold examination (VIBE))
      sequence was acquired in the axial plane only. Acquisition and 3D review were
      controlled under sterile conditions with a panel inside the examination room
      (Syngo; Siemens). RESULTS: The 3D FLASH sequence significantly decreased the mean
      number of acquisitions needed to place the microcatheter with the titanium needle
      in the metastasis compared to interventions with the 2D FLASH sequence (2.9 +/-
      0.83 vs. 4.4 +/- 1.63). With 2D FLASH imaging, acquisition in a second plane was
      necessary in 78 instances (20% of acquired 2D sequences) to ensure adequate
      positioning of the device during the procedure. The artifact caused by the
      titanium needle was smaller with the 3D FLASH sequence. The conspicuity of liver
      metastases and morphology (liver edge and vessels) was acceptable with both
      sequences. The 3D FLASH sequence improved differentiation when two to four
      titanium needles were inserted, due to smaller susceptibility artifacts caused by
      the needles. CONCLUSION: 3D GRE imaging with the capability to perform
      multiplanar reconstruction (MPR) shortens the procedure by reducing the number of
      sequences needed. Improved visibility of the titanium needles allows more precise
      insertion of multiple needles into the metastasis.

PMID- 17520738
TI  - In vivo magnetic resonance imaging of iron oxide-labeled, arterially-injected
      mesenchymal stem cells in kidneys of rats with acute ischemic kidney injury:
      detection and monitoring at 3T.
AB  - PURPOSE: To evaluate MRI for a qualitative and quantitative in vivo tracking of
      intraaortal injected iron oxide-labeled mesenchymal stem cells (MSC) into rats
      with acute kidney injury (AKI). MATERIALS AND METHODS: In vitro MRI and R2*
      measurement of nonlabeled and superparamagnetic iron oxide (SPIO)-labeled MSC
      (MSC(SPIO)) was performed in correlation to cellular iron content and cytological
      examination (Prussian blue, electron microscopy). In vivo MRI and R2* evaluation
      were performed before and after ischemic/reperfusion AKI (N = 14) and intraaortal
      injection of 1.5 x 10(6) MSC(SPIO) (N = 7), fetal calf serum (FCS) (medium, N =
      6), and SPIO alone (N = 1) up to 14 days using a clinical 3T scanner. Signal to
      noise ratios (SNR), R2* of kidneys, liver, spleen, and bone marrow, renal
      function (creatinine [CREA], blood urea nitrogen [BUN]), and kidney volume were
      measured and tested for statistical significance (Student's t-test, P < 0.05) in
      comparison histology (hematoxylin and eosin [H&E], Prussian blue, periodic acid
      Schiff [PAS], CD68). RESULTS: In vitro, MSC(SPIO) showed a reduction of SNR and
      T2* with R2* approximately number of MSC(SPIO) (R2 = 0.98). In vivo MSC(SPIO)
      administration resulted in a SNR decrease (35 +/- 15%) and R2* increase (101 +/-
      18.3%) in renal cortex caused by MSC(SPIO) accumulation in contrast to control
      animals (P < 0.01). Liver, spleen, and bone marrow (MSC(SPIO)) showed a delayed
      SNR decline/R2* increase (P < 0.05) resulting from MSC(SPIO) migration. The
      increase of kidney volume and the decrease in renal function (P < 0.05) was
      reduced in MSC-treated animals. CONCLUSION: Qualitative and quantitative in vivo
      cell-tracking and monitoring of organ distribution of intraaortal injected
      MSC(SPIO) in AKI is feasible in MRI at 3T.

PMID- 17520739
TI  - Staining methods for magnetic resonance microscopy of the rat fetus.
AB  - PURPOSE: To develop a magnetic resonance histology (MRH) staining and fixation
      method by immersion to enhance the signal-to-noise ratio (SNR) with a
      paramagnetic contrast agent permitting microscopic acquisition within a 3-hour
      scan time. MATERIALS AND METHODS: Methods were optimized for embryonic day 18.5
      (E18.5) rat fetuses and imaging at 9.4T with an RF refocused spin-echo pulse
      sequence (TR/TE = 75 msec/5.2 msec). Fixation/staining was performed by immersion
      in Bouin's fixative containing varied concentrations of ProHance (from 10:1 to
      500:1 Bouin's:ProHance) and for varied immersion durations (up to 24 hours).
      RESULTS: The results showed a significant change in T1 and T2 relaxation times as
      a function of concentration of contrast agent and immersion duration. As the
      contrast agent penetrated the tissues, T1 was reduced as desired (typically by
      10x), but at the same time T2 was profoundly reduced (typically by 3x) due to
      both protein cross-linking from the fixative and the high concentration of
      contrast agent. A systematic assessment of this staining protocol showed an
      increased SNR (by 5x) over that in unstained specimens. CONCLUSION: This staining
      protocol reduced scan time for very-high-resolution images (19.5 microm) to only
      3 hours, making MRH a routine tool for evaluating fetal development.

PMID- 17520740
TI  - Black-blood T2* technique for myocardial iron measurement in thalassemia.
AB  - PURPOSE: To compare the effectiveness and reproducibility of a new black-blood
      sequence vs. a conventional bright-blood gradient-echo T2* sequence for
      myocardial iron overload measurement in thalassemia. MATERIALS AND METHODS:
      Twenty thalassemia patients were studied. Black-blood sequence images were
      acquired in diastole after a double inversion recovery (DIR) preparation pulse.
      Bright-blood sequence images were acquired in both early systole and late
      diastole. The data were randomized and the T2* analysis was performed blindly by
      two independent observers. RESULTS: The T2* values from the black-blood sequence
      were comparable to those of the conventional bright-blood sequence (25.7 +/- 12.9
      msec vs. 26.4 +/- 14.2 msec in early systole, P = 0.44; and 25.2 +/- 13.1 msec in
      late diastole, P = 0.41). The coefficient of variation (CV) for black-blood image
      T2* analysis was 4.1% compared with 8.9% (early systole P = 0.03) and 7.8% (late
      diastole P = 0.05) for bright-blood image analysis. CONCLUSION: The black-blood
      T2* technique yields high-contrast myocardial images, provides clearly depicted
      myocardial borders, and avoids blood signal contamination of the myocardium while
      yielding improvements in interobserver variability.

PMID- 17520741
TI  - Dependence of vessel area accuracy and precision as a function of MR imaging
      parameters and boundary detection algorithm.
AB  - PURPOSE: To determine the appropriate image acquisition parameters for an
      accurate measurement of vessel cross-sectional area from MR angiography (MRA)
      images. MATERIALS AND METHODS: A series of images with different vessel cross
      sectional areas, resolutions, and signal-to-noise ratios (SNRs) were simulated
      and validated experimentally. Dynamic programming (DP) was employed to determine
      the accuracy and precision of the vessel cross-sectional area as a function of
      vessel size, sampling matrix, acquisition time, and postprocessing parameters
      such as zooming and bias correction. RESULTS: We show that there is an optimal
      value of lambda (the ratio of vessel diameter to resolution) for a given
      intrinsic SNR that yields the most accurate and precise area measurement.
      Specifically, when the SNR is > or =10:1, this value of lambda is 8 and yields a
      cross-sectional area error of <5% with a zoom factor of > or =2. CONCLUSION: The
      predicted ideal result of lambda = 8 is within reach with current technology to
      image vessels such as the carotid artery or aorta. It is possible to determine
      the ideal resolution that minimizes errors in the measurement of the vessel cross
      sectional area for a given SNR, processing algorithm, and vessel of interest.

PMID- 17520742
TI  - Hepatic encephalopathy as a predictor of survival in patients with end-stage
      liver disease.
AB  - Hepatic encephalopathy (HE) is an important component of hepatic decompensation,
      which reduces survival in patients with cirrhosis. The Model for End-Stage Liver
      Disease (MELD) score has been used to predict survival of patients with
      cirrhosis. The aims of this study were to determine whether HE is a predictor of
      survival of patients with cirrhosis and to examine the degree to which HE may add
      to the survival prediction of MELD. Patients with end-stage liver disease whose
      data were included in 2 databases were included in the analysis: 223 patients
      undergoing transjugular intrahepatic portosystemic shunt (TIPS) insertion, and
      271 patients hospitalized with hepatic decompensation. In univariate analysis, HE
      grade 3 or higher was associated with a 3.7-fold (95% confidence interval, 1.9
      7.3, P<0.01) increase in the risk of death in the TIPS patients and HE grade 2 or
      higher was associated 3.9-fold increase (95% confidence interval [95% CI], 2.6
      5.7, P<0.01) in hospitalized patients. As expected, MELD and Child-Turcotte-Pugh
      scores (with and without HE included) were also markedly associated with
      survival. When HE (grade 2 or higher) and MELD were considered together, HE
      remained strongly statistically significant in the hospitalized patients (hazard
      ratio=2.6, 95% CI, 1.7-3.8, P<0.01). The effect became smaller in the TIPS
      patients (hazard ratio=1.1; 95% CI, 0.7-1.6, P=0.76). In conclusion, this
      retrospective study demonstrates that HE is an important event in the natural
      history of cirrhosis that affects subsequent survival of patients. HE may provide
      additional prognostic information independent of MELD, which warrants prospective
      validation.

PMID- 17520743
TI  - Natural history of unexplained chronic hepatitis after liver transplantation.
AB  - Unexplained chronic hepatitis (CH) in the adult liver allograft recipient is not
      uncommon, but its natural history and clinical significance is unknown. A
      retrospective study was undertaken of adult liver allograft recipients to
      determine the frequency and natural history of unexplained CH. We evaluated only
      those patients who had undergone >or=2 liver biopsies after 6 months and were
      grafted for indications where recurrent disease could be confidently excluded
      (alcoholic liver disease [ALD] in those who remained abstinent and fulminant
      hepatic failure [FHF] from drug reactions). Of 288 patients who were transplanted
      for ALD or FHF, 30 fulfilled the above criteria. CH was first diagnosed at a
      median of 15.25 months after transplantation. A total of 24 patients showed mild
      necroinflammatory changes, and 12 had mild or moderate fibrosis. Liver tests did
      not reflect the presence or degree of inflammation or fibrosis. After a median of
      4 years, necroinflammatory scores were increased in 5; new or progressive
      fibrosis was noted in 13%; 3 had developed cirrhosis; and 5 developed clinical
      evidence of portal hypertension. Progressive fibrosis was associated with a high
      titer of anti-nuclear antibodies (>1:1600) and a portal tract plasma cell
      infiltrate. There was a trend for correlation between necroinflammatory activity
      and fibrosis stage, but this did not reach statistical significance (P = 0.06).
      Serum alkaline phosphatase (P = 0.012) and female gender of the donor (P = 0.033)
      were associated with progressive fibrosis. Unexplained CH is not uncommon in the
      liver allograft and may progress to established cirrhosis in a subgroup of
      patients transplanted for ALD or FHF. Standard liver tests do not reflect the
      extent of these changes, so protocol liver biopsies may be required to detect
      these changes. We recommend careful history and follow-up in these patients.

PMID- 17520744
TI  - Central nervous system juvenile xanthogranuloma with malignant transformation.
AB  - Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder that typically
      manifests in the skin. Here, we describe a patient with JXG diffusely involving
      the central nervous system (CNS), whose disease responded to therapy but
      subsequently underwent dissemination to the peritoneum and bone marrow. Repeat
      biopsy at dissemination revealed pleomorphic histiocytes with tetraploidy,
      suggesting evolution to a clonal histiocytic neoplasm. Despite further
      chemotherapy, the patient died of disease progression. This case highlights the
      clinical and pathological heterogeneity of JXG and the difficulty of treating
      multi-focal CNS disease.

PMID- 17520745
TI  - Flavoprotein autofluorescence imaging in the cerebellar cortex in vivo.
AB  - Autofluorescence optical imaging is rapidly becoming a widely used tool for
      mapping activity in the central nervous system function in vivo and investigating
      the coupling among neurons, glia, and metabolism. This paper provides a brief
      review of autofluorescence and of our recent work using flavoprotein imaging in
      the cerebellar cortex. Stimulation of the parallel fibers evokes an intrinsic
      fluorescence signal that is tightly coupled to neuronal activation and primarily
      generated postsynaptically. The signal originates from mitochondrial
      flavoproteins. The signal is biphasic, with the initial increase in fluorescence
      (light phase) resulting from the oxidation of flavoproteins and the subsequent
      decrease (dark phase) from the reduction of flavoproteins. The light phase is
      primarily neuronal, and the dark phase is primarily glial. Exploiting the spatial
      properties of molecular layer inhibition in the cerebellar cortex, we show that
      flavoprotein autofluorescence can monitor both excitatory and inhibitory activity
      in the cerebellar cortex. Furthermore, flavoprotein autofluorescence has revealed
      that molecular layer inhibition is organized into parasagittal domains that
      differentially modulate the spatial pattern of cerebellar cortical activity. The
      reduction in flavoprotein autofluorescence occurring in the inhibitory bands most
      likely reflects a decrease in intracellular Ca(2+) in the neurons inhibited by
      the molecular layer interneurons. Therefore, flavoprotein autofluorescence
      imaging is providing new insights into cerebellar cortical function and
      neurometabolic coupling.

PMID- 17520746
TI  - Copper activates TrkB in cortical neurons in a metalloproteinase-dependent
      manner.
AB  - Copper (Cu) is an endogenous metal that is physiologically essential in the brain
      and that, like zinc (Zn), may be synaptically released in certain regions.
      Previously, we demonstrated that Zn activates TrkB in cultured cortical neurons
      in a metalloproteinase (MP)-dependent manner. To determine whether Cu has similar
      properties, we exposed cortical cultures for 15 min to various metals and
      performed Western blots to detect tyrosine-phosphorylated TrkB (p-Trk). Whereas
      Cd, Mn, Fe(II), and Fe(III) had no effect on the level of p-Trk, 10 microM of Cu
      in phosphate-containing (Hanks' balanced salt solution) or 10 nM in phosphate
      lacking salt solution (control salt solution), increased levels of p-Trk. Cu also
      activated extracellular signal-regulated kinase 1/2 and Src tyrosine kinase,
      signaling molecules activated downstream of TrkB. Cu decreased levels of probrain
      derived neurotrophic factor (pro-BDNF) in cells but increased levels of pro- and
      mature BDNF in the media. Addition of MP inhibitors completely blocked the Cu
      induced increases in pro-BDNF and BDNF as well as TrkB activation, indicating
      that MP mediates most of the Cu effect. Furthermore, Cu increased the activity of
      matrix metalloproteinase 2 (MMP2) and MMP9 in cortical neurons. These findings
      indicate that, like Zn, Cu activates MPs, releases pro-BDNF from cells, and
      phosphorylates TrsB. Because Cu, like Zn, is released in certain brain areas with
      neuronal activity, metal-triggered TrkB activation may occur in both Cu- and Zn
      containing synapses.

PMID- 17520747
TI  - Enhanced neuronal differentiation in a three-dimensional collagen-hyaluronan
      matrix.
AB  - Efficient 3D cell systems for neuronal induction are needed for future use in
      tissue regeneration. In this study, we have characterized the ability of neural
      stem/progenitor cells (NS/PC) to survive, proliferate, and differentiate in a
      collagen type I-hyaluronan scaffold. Embryonic, postnatal, and adult NS/PC were
      seeded in the present 3D scaffold and cultured in medium containing epidermal
      growth factor and fibroblast growth factor-2, a condition that stimulates NS/PC
      proliferation. Progenitor cells from the embryonic brain had the highest
      proliferation rate, and adult cells the lowest, indicating a difference in
      mitogenic responsiveness. NS/PC from postnatal stages down-regulated nestin
      expression more rapidly than both embryonic and adult NS/PC, indicating a faster
      differentiation process. After 6 days of differentiation in the 3D scaffold,
      NS/PC from the postnatal brain had generated up to 70% neurons, compared with 14%
      in 2D. NS/PC from other ages gave rise to approximately the same proportion of
      neurons in 3D as in 2D (9-26% depending on the source for NS/PC). In the
      postnatal NS/PC cultures, the majority of betaIII-tubulin-positive cells
      expressed glutamate, gamma-aminobutyric acid, and synapsin I after 11 days of
      differentiation, indicating differentiation to mature neurons. Here we report
      that postnatal NS/PC survive, proliferate, and efficiently form synapsin I
      positive neurons in a biocompatible hydrogel.

PMID- 17520748
TI  - Ribosomal distributions in axons of mammalian myelinated fibers.
AB  - The distribution of ribosomes and polysomes in uninjured myelinated axons of rat
      sciatic nerve was analyzed. Ribosomes were identified by immunocytochemistry at
      the light and electron microscopic levels. A polyclonal antibody developed
      against ribosomes recognized both rRNA and ribosomal proteins. The distribution
      of the immunoreaction product was similar to that obtained with human anti
      ribosomal P protein. The immunoreaction product distributions were of two types
      in axons: 1) periodic localization in the cortical region of axoplasm that
      appeared as a compact structural aggregate, consistent with that described as a
      periaxoplasmic ribosomal plaques (PARP) domain (Koenig et al. [2000] J. Neurosci.
      20:8390-8400), and 2) scattered small immuno-reactive clusters of varying sizes
      (RNP) within the central core of the axon. The latter observation suggested the
      possibility that RNP-like particles could be associated with the axonal transport
      system and in transit. Immunoreaction product was also associated with a novel
      structural inclusion, possibly multi-vesicular in makeup that was located in the
      axon and at the myelin-axon interface, and visible at the light and EM levels.
      The potential significance of this structural peculiarity is considered.

PMID- 17520750
TI  - Vomiting after minor head injury: is it a serious sign?

PMID- 17520751
TI  - Poison safety. New parents urged to adopt lifesaving routines to prevent
      poisonings.

PMID- 17520752
TI  - Comparing effectiveness of pain relievers in children.

PMID- 17520753
TI  - Vaccinations: one more has been added...but a combination vaccine could reduce
      the number of shots.

PMID- 17520754
TI  - Title I--improving the academic achievement of the disadvantaged; Individuals
      with Disabilities Education Act (IDEA)--assistance to states for the education of
      children with disabilities. Final regulations.
AB  - The Secretary amends the regulations governing programs administered under Title
      I of the Elementary and Secondary Education Act of 1965 (ESEA), as amended by the
      No Child Left Behind Act of 2001 (NCLB) (referred to in these regulations as the
      Title I program) and the regulations governing programs under Part B of the
      Individuals with Disabilities Education Act (IDEA) (referred to in these
      regulations as the IDEA program). These regulations provide States with
      additional flexibility regarding State, local educational agency (LEA), and
      school accountability for the achievement of a small group of students with
      disabilities whose progress is such that, even after receiving appropriate
      instruction, including special education and related services designed to address
      the students' individual needs, the students' individualized education program
      (IEP) teams (IEP Teams) are reasonably certain that the students will not achieve
      grade-level proficiency within the year covered by the students' IEPs.

PMID- 17520755
TI  - Intra-articular hyaluronic acid (viscosupplementation) for hip osteoarthritis.
AB  - In viscosupplementation, a glycosaminoglycan called hyaluronic acid (HA) is
      administered via intra-articular injection to patients with osteoarthritis (OA).
      Two systematic reviews found that HA for hip OA may relieve pain and improve
      function. Randomized controlled trials had differing results. Uncontrolled
      studies suggest that there are moderate improvements regarding pain and function
      for three to six months after HA injection. There is no evidence regarding the
      cost-effectiveness of this therapy. No serious adverse events have been reported
      after intra-articular injection of HA for hip OA. The best available evidence
      suggests that HA may offer symptomatic relief in patients with mild to moderate
      hip OA for whom other conservative therapies are contraindicated or have failed.
      Currently, there is insufficient good quality evidence to determine this
      conclusively.

PMID- 17520756
TI  - Medicare program; competitive acquisition for certain durable medical equipment,
      prosthetics, orthotics, and supplies (DMEPOS) and other issues. Final rule.
AB  - This final rule establishes competitive bidding programs for certain Medicare
      Part B covered items of durable medical equipment, prosthetics, orthotics, and
      supplies (DMEPOS) throughout the United States in accordance with sections
      1847(a) and (b) of the Social Security Act. These competitive bidding programs,
      which will be phased in over several years, utilize bids submitted by DMEPOS
      suppliers to establish applicable payment amounts under Medicare Part B.

PMID- 17520757
TI  - Control of a chemical precursor used in the illicit manufacture of fentanyl as a
      List I chemical. Interim rule with request for comments.
AB  - This rulemaking controls the chemical N-phenethyl-4-piperidone (NPP) as a List I
      chemical under the Controlled Substances Act (CSA) (21 U.S.C. 801 et seq.).
      Clandestine laboratories are using this chemical to illicitly manufacture the
      schedule II controlled substance fentanyl. The recent distribution of illicitly
      manufactured fentanyl has caused an unprecedented outbreak of hundreds of
      suspected fentanyl-related overdoses, at least 972 confirmed fentanyl-related
      deaths, and 162 suspected fentanyl-related deaths occurring mostly in Delaware,
      Illinois, Maryland, Michigan, Missouri, New Jersey, and Pennsylvania. NPP has
      been identified as the starting material in several seized fentanyl clandestine
      laboratories. In addition to DEA's concern regarding the deaths associated with
      illicitly manufactured fentanyl, DEA is extremely concerned about the safety of
      law enforcement officers encountering these clandestine laboratories. Therefore,
      DEA is regulating NPP as a List I chemical through this Interim Rulemaking. DEA
      is soliciting comments on this Interim Rule. This rulemaking will subject
      handlers of NPP to the chemical regulatory provisions of the CSA and its
      implementing regulations, including 21 CFR Parts 1309, 1310, 1313, and 1316. This
      rulemaking does not establish a threshold for domestic and international
      transactions of NPP. As such, all transactions involving NPP, regardless of size,
      shall be regulated. This rulemaking also specifies that chemical mixtures
      containing NPP will not be exempt from regulatory requirements at any
      concentration. Therefore, all transactions of chemical mixtures containing any
      quantity of NPP will be regulated and will be subject to control under the CSA.

PMID- 17520758
TI  - Office of the Assistant Secretary for Preparedness and Response; HHS Public
      Health Emergency Medical Countermeasures Enterprise implementation plan for
      chemical, biological, radiological and nuclear threats. Notice.
AB  - The United States faces serious public health threats from the deliberate use of
      weapons of mass destruction (WMD)--chemical, biological, radiological, or nuclear
      (CBRN)--by hostile States or terrorists, and from naturally emerging infectious
      diseases that have a potential to cause illness on a scale that could adversely
      impact national security. Effective strategies to prevent, mitigate, and treat
      the consequences of CBRN threats is an integral component of our national
      security strategy. To that end, the United States must be able to rapidly
      develop, stockpile, and deploy effective medical countermeasures to protect the
      American people. The HHS Public Health Emergency Medical Countermeasures
      Enterprise (PHEMCE) has taken a holistic, end-to-end approach that considers
      multiple aspects of the medical countermeasures mission including research,
      development, acquisition, storage, maintenance, deployment, and guidance for
      utilization. Phase one of this approach established the HHS PHEMCE Strategy for
      Chemical, Biological, Radiological, and Nuclear Threats (HHS PHEMCE Strategy).
      The HHS PHEMCE Strategy, published in the Federal Register on March 20, 2007,
      described a framework of strategic policy goals and objectives for identifying
      medical countermeasure requirements and establishing priorities for medical
      countermeasure evaluation, development and acquisition. These strategic policy
      goals and objectives were used to establish the Four Pillars upon which this HHS
      Public Health Emergency Medical Countermeasures Enterprise Implementation Plan
      (HHS PHEMCE Implementation Plan) is based. The HHS PHEMCE Implementation Plan
      considers the full spectrum of medical countermeasures-related activities,
      including research, development, acquisition, storage/maintenance, deployment,
      and utilization. The HHS PHEMCE Implementation Plan is consistent with the
      President's Biodefense for the 21st Century and is aligned with the National
      Strategy for Medical Countermeasures against Weapons of Mass Destruction.

PMID- 17520759
TI  - Myopathy, noncompaction, and the Takotsubo phenomenon in congenital contractural
      arachnodactyly (Beals syndrome).

PMID- 17520760
TI  - Patient-reported factors associated with discontinuing employment following head
      and neck cancer treatment.
AB  - OBJECTIVE: To evaluate patients' reported reasons for discontinuing employment
      following treatment for head and neck cancer (HNC). Discontinuing employment is a
      serious problem for patients with HNC and has an impact on many aspects of their
      lives. DESIGN: Prospective, observational outcomes study. SETTING: Tertiary care
      institution. PATIENTS: A total of 666 patients with carcinomas of the head and
      neck who were treated from January 1, 1998, to October 31, 2004. INTERVENTIONS:
      Patients provided information about the status of their employment at the time of
      diagnosis and then at 3, 6, 9, and 12 months after diagnosis. Patients who
      discontinued employment after treatment rated the importance of 5 factors
      (eating, speech, appearance, pain or discomfort, and fatigue) in that decision.
      MAIN OUTCOME MEASURES: The 5 factors were scored on a 5-point Likert scale (5
      being most important) as to their importance in the decision to discontinue work.
      The relationships of patient, disease, and treatment variables to employment
      status were evaluated. RESULTS: Of the 666 patients, 239 were employed at the
      time of their diagnosis. After treatment, 91 (38.1%) of the 239 reported
      discontinuing work because of their cancer and treatment. Eighty-two (90.1%) of
      these 91 patients rated each of the 5 factors. Fatigue had the highest percentage
      (58.5%) of 4 or 5 ratings, followed by speech (51.2%), eating (45.1%), pain or
      discomfort (37.8%), and appearance (17.1%). Thirty-seven (40.7%) of the 91
      patients who discontinued work returned to work within 1 year of treatment.
      CONCLUSION: Identification of the factors associated with the decision to
      discontinue work is a first step in providing focused solutions to minimize
      disability.

PMID- 17520761
TI  - General health measures and long-term survival in patients with head and neck
      cancer.
AB  - OBJECTIVE: To determine whether a self-reported, subjective general health
      assessment tool can provide prognostic information about survival in patients
      with head and neck cancer. DESIGN: Prospective observational cohort study.
      SETTING: Tertiary care center. PATIENTS: Five hundred seventy-one patients with
      squamous cell carcinoma of the upper aerodigestive tract who were enrolled in the
      institution's longitudinal Outcomes Assessment Project between January 1, 1995,
      and November 30, 2004. MAIN OUTCOME MEASURES: Actuarial 5-year observed and
      disease-specific survival. RESULTS: The physical component summary obtained from
      the SF-36 (Medical Outcomes Study 36-Item Short-Form Health Survey) was
      significantly associated with ACE-27 (Adult Comorbidity Evaluation-27)
      comorbidity ratings. The mental component summary was not associated with ACE-27
      scores or survival. Although the comorbidity rating was an independent predictor
      of observed survival (P = .002) only, the physical component summary was
      independently predictive of both observed (P<.001) and disease-specific (P =
      .001) survival. These associations continued to be independently significant when
      site and stage were included in the analysis (P = .003, P<.001, and P = .004,
      respectively). CONCLUSION: The physical component summary generated by the SF-36,
      a self-reported, subjective measure of general physical health, is predictive of
      both observed and disease-specific survival.

PMID- 17520762
TI  - Incidence of vocal cord paralysis with and without recurrent laryngeal nerve
      monitoring during thyroidectomy.
AB  - OBJECTIVE: To compare the incidence of postoperative vocal cord paresis or
      paralysis in a cohort of patients who underwent thyroidectomy with and without
      continuous recurrent laryngeal nerve (RLN) monitoring by a single senior surgeon.
      We hypothesize that continuous RLN monitoring reduces the rate of nerve injury
      during thyroidectomy DESIGN: Retrospective medical chart review. SETTING:
      Academic tertiary care medical center. PATIENTS: A total of 684 patients (1043
      nerves at risk) who underwent thyroid surgery under general anesthesia. MAIN
      OUTCOME MEASURE: Incidence of vocal cord paresis or paralysis in patients who
      underwent thyroid surgery with continuous RLN monitoring vs those undergoing
      surgery without continuous RLN monitoring. RESULTS: The incidence of unexpected
      unilateral vocal cord paresis based on RLNs at risk was 2.09% (n = 14) in the
      monitored group and 2.96% (n = 11) in the unmonitored group. This difference was
      not statistically significant. The incidence of unexpected complete unilateral
      vocal cord paralysis was 1.6% in each group. Two of the 5 paralyses in the
      unmonitored group and 7 of the 11 paralyses in the monitored group had complete
      resolution. CONCLUSIONS: Monitoring of the RLN does not appear to reduce the
      incidence of postoperative temporary or permanent complete vocal cord paralysis.
      There appeared to be a slightly lower rate of postoperative paresis with RLN
      monitoring, but this difference was not statistically significant.

PMID- 17520763
TI  - Superselective neck dissection after chemoradiation: feasibility based on
      clinical and pathologic comparisons.
AB  - OBJECTIVE: To determine whether superselective neck dissection (removal of 2 or
      less contiguous neck levels) is effective salvage surgery for patients with
      residual single-level adenopathy after concomitant intra-arterial cisplatin and
      radiotherapy. DESIGN: Analysis of prospectively collected data. SUBJECTS: The
      study group comprised 177 patients (239 heminecks) with N+ disease.
      INTERVENTIONS: Intra-arterial treatment with cisplatin (150 mg/m2) on days 1, 8,
      15, and 22 and radiation therapy (2 Gy/d) 5 times per week for 7 weeks.
      Comparisons were made between neck-level-specific disease at restaging and
      pathologic disease after neck dissection. RESULTS: Tumor sites included
      oropharynx (n = 81), hypopharynx (39), larynx (n=27), oral cavity (n = 19), and
      other (n = 11). Response of nodal disease based on clinical evaluation was as
      follows: complete response, 89 patients (50%); partial response, 81 patients
      (46%); progressive disease, 4 patients (2%); and unevaluable, 3 patients (2%). Of
      the 89 patients whose necks were restaged as a partial response, 73 had clinical
      evidence of residual adenopathy involving only 1 neck level. Within this subset,
      54 patients (57 heminecks) subsequently underwent a salvage neck dissection, for
      which comparisons were made between the restaging evidence of residual adenopathy
      and the pathologic findings that were specific for each neck level. Only 2 of the
      54 patients had evidence of pathologic disease extending beyond the single neck
      level: one had disease in a contiguous neck level, and the other had disease in a
      noncontiguous level. The use of superselective neck dissection with removal of
      only 2 contiguous neck levels would have encompassed known disease in all but 1
      patient. CONCLUSION: Superselective neck dissection is feasible after this
      specific chemoradiation protocol has been administered to patients with
      persistent nodal disease that is confined to 1 level.

PMID- 17520764
TI  - Pectoralis major flap in composite lateral skull base defect reconstruction.
AB  - OBJECTIVE: To report our experience with the pectoralis major myocutaneous flap
      (PMF) for the reconstruction of composite lateral temporal bone defects extending
      beyond the temporal line. DESIGN: Retrospective review and illustration of
      specific technical modifications. SETTING: Academic tertiary care center.
      PATIENTS: Eight patients with composite lateral skull base defects that were
      reconstructed with the PMF between February 2001 and February 2006. INTERVENTION:
      Reconstruction with the modified pedicled PMF. MAIN OUTCOME MEASURES:
      Reconstruction outcomes and complications. RESULTS: Eight patients (median age,
      80 years) underwent total or near-total auriculectomy, wide skin excision, and
      lateral temporal bone resection as part of the surgical ablation, thus requiring
      obliteration of the middle ear cavity as well as extensive replacement of skin
      cover. All patients received radiation therapy. The median postsurgical follow-up
      was 9 months. Complete healing of the reconstructed surgical defect with no flap
      loss was achieved in all cases. CONCLUSION: With specific technical
      modifications, the PMF can be reliably used for the reconstruction of composite
      lateral skull base defects extending up to and beyond the temporal line, making
      this flap an important alternative to free flap reconstruction in selected cases.

PMID- 17520765
TI  - The Kidney Research Scientist Core Education and National Training (KRESCENT)
      Program.

PMID- 17520766
TI  - Sensitivity and specificity of fluorescent immunoguided neoplasm detection in
      head and neck cancer xenografts.
AB  - OBJECTIVES: To determine whether fluorescently labeled anti-epidermal growth
      factor (EGFR) antibody could be used to detect residual disease and to guide
      surgical resections by comparing the sensitivity and specificity of optical
      fluorescence imaging with the sensitivity and specificity of histopathologic
      evaluation. DESIGN: A preclinical model of head and neck squamous cell carcinoma.
      SUBJECTS: Mice xenografted with SCC-1 tumor cells. INTERVENTIONS: The mice
      underwent systemic injection with anti-EGFR antibody (cetuximab) conjugated to an
      optically active fluorophore (Cy5.5). Both a subcutaneous flank model (n = 18)
      and an orthotopic murine model (n = 15) were used to assess for the presence of
      residual disease by fluorescent stereomicroscopy after subtotal resections of
      tumors. Histologic analysis was performed to confirm the presence or absence of
      disease. RESULTS: In the subcutaneous flank model, a diagnostic dose (50 microg)
      and therapeutic dose (250 microg) of fluorescent-labeled anti-EGFR were
      administered. When a diagnostic dose was given, the sensitivity was 86%, which
      was less than the 91% sensitivity when the higher dose was given. Tumor biopsy
      specimens in which disease was detected by histologic analysis but not by
      fluorescence (false-negative result) averaged 166 cells (range, 50-350 cells).
      The specificity of optical fluorescence to predict the presence of tumor in both
      groups was 100%. In the floor of the mouth model, we demonstrated a sensitivity
      of 81% and a specificity of 100%. False-negative results were obtained in a tumor
      fragment measuring less than 0.5 mm in diameter. CONCLUSION: These data support
      further investigation of fluorescently labeled anti-EGFR antibody to detect
      disease in the surgical setting.

PMID- 17520767
TI  - Medical devices; obstetrical and gynecological devices; classification of
      computerized labor monitoring system. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the computerized labor
      monitoring systems into class II (special controls). Elsewhere in this issue of
      the Federal Register, FDA is announcing the availability of a guidance document
      entitled, "Guidance for Industry and FDA Staff; Class II Special Controls
      Guidance Document: Computerized Labor Monitoring Systems," which will serve as
      the special controls for these devices. The agency is classifying these devices
      into class II (special controls) in order to provide a reasonable assurance of
      safety and effectiveness of these devices.

PMID- 17520768
TI  - Risk behaviours for infection with HIV and hepatitis C virus among people who
      inject drugs in Regina, Saskatchewan.

PMID- 17520769
TI  - Privacy and disclosure of official records and information. Final rules.
AB  - These final rules revise our privacy and disclosure rules to clarify certain
      provisions and to provide expanded regulatory support for new and existing
      responsibilities and functions. These changes in the regulations will increase
      Agency efficiency and ensure consistency in the implementation of the Social
      Security Administration's (SSA) policies and responsibilities under the Privacy
      Act and the Social Security Act.

PMID- 17520770
TI  - Use of ozone-depleting substances; removal of essential use designations;
      confirmation of effective date. Direct final rule; confirmation of effective
      date.
AB  - The Food and Drug Administration (FDA) is confirming the effective date of April
      23, 2007, for the direct final rule that appeared in the Federal Register of
      December 7, 2006 (71 FR 70870). The direct final rule amends the regulation to
      remove beclomethasone, dexamethasone, fluticasone, bitolterol, salmeterol,
      ergotamine tartrate, and ipratropium bromide, used in oral pressurized metered
      dose inhalers, from the list of essential uses of ozone-depleting substances.
      None of these products is currently being marketed. This document confirms the
      effective date of the direct final rule.

PMID- 17520771
TI  - Data collection related to the participation of faith-based and community
      organizations. Final rule.
AB  - This final rule is part of the Department's effort to fulfill its
      responsibilities under the Faith-Based and Community Initiative pursuant to
      Executive Orders 13279 and 13280. Under this rule, State agencies will collect
      and report information related to institutions and organizations that participate
      in specified Food and Nutrition Service (FNS) nutrition assistance programs. This
      information will be a new collection for the affected programs. It will enable
      FNS to identify the faith-based and community organizations participating in
      Federal nutrition assistance programs and determine the level of participation of
      faith-based and community organizations in the programs. It will not adversely
      impact the application or participation of any organization or institution
      currently participating in, or seeking to participate in, FNS nutrition
      assistance programs.

PMID- 17520772
TI  - Case series descriptive analysis of a primary syphilis outbreak in Edmonton,
      Alberta, July 2004-April 2006.

PMID- 17520773
TI  - Statement on human papillomavirus vaccine. An Advisory Committee Statement (ACS).

PMID- 17520774
TI  - Statement on conjugate meningococcal vaccine for serogroups   A, C, Y and W135.
      An Advisory Committee Statement (ACS).

PMID- 17520775
TI  - Schedules of controlled substances: placement of lisdexamfetamine into schedule
      II. Final rule.
AB  - With the issuance of this final rule, the Deputy Administrator of the Drug
      Enforcement Administration (DEA) places the substance lisdexamfetamine, including
      its salts, isomers and salts of isomers into schedule II of the Controlled
      Substances Act (CSA). As a result of this rule, the regulatory controls and
      criminal sanctions of schedule II will be applicable to the manufacture,
      distribution, dispensing, importation and exportation of lisdexamfetamine and
      products containing lisdexamfetamine.

PMID- 17520776
TI  - The immunocompromised traveller. An Advisory Committee Statement (ACS).

PMID- 17520777
TI  - Statement on high-altitude illnesses. An Advisory Committee Statement (ACS).

PMID- 17520778
TI  - Medical devices; immunology and microbiology devices; classification of gene
      expression profiling test system for breast cancer prognosis. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying gene expression profiling
      test systems for breast cancer prognosis into class II (special controls). The
      special control that will apply to the device is the guidance document entitled
      "Class II Special Controls Guidance Document: Gene Expression Profiling Test
      System for Breast Cancer Prognosis." The agency is classifying the device into
      class II (special controls) in order to provide a reasonable assurance of safety
      and effectiveness of the device. Elsewhere in this issue of the Federal Register,
      FDA is announcing the availability of the guidance document that will serve as
      the special control for this device.

PMID- 17520779
TI  - Medicare program; prospective payment system for long-term care hospitals RY
      2008: annual payment rate updates, and policy changes; and hospital direct and
      indirect graduate medical education policy changes. Final rule.
AB  - This final rule updates the annual payment rates for the Medicare prospective
      payment system (PPS) for inpatient hospital services provided by long-term care
      hospitals (LTCHs). The final payment amounts and factors used to determine the
      updated Federal rates that are described in this final rule were determined based
      on the LTCH PPS rate year July 1, 2007 through June 30, 2008. The annual update
      of the long-term care diagnosis-related group (LTC-DRG) classifications and
      relative weights remains linked to the annual adjustments of the acute care
      hospital inpatient diagnosis-related group system, and continue to be effective
      each October 1. The final outlier threshold for July 1, 2007, through June 30,
      2008, is derived from the LTCH PPS rate year calculations. We are also finalizing
      policy changes which include revisions to the GME and IME policies. In addition,
      we are adding a technical amendment correcting the regulations text at Sec.
      412.22.

PMID- 17520780
TI  - Esophageal motility testing: the spastic truth.

PMID- 17520781
TI  - Toward comprehensive interdisciplinary academic sleep centers.

PMID- 17520782
TI  - Computation of attributable fractions on the basis of exposure probabilities.

PMID- 17520784
TI  - Number and function of circulating human antigen presenting cells regulated by
      sleep.
AB  - STUDY OBJECTIVES: There is evidence that sleep facilitates the adaptive immune
      response to infectious agents and, thereby, supports immunologic memory. The
      effect might be attained by sleep-induced changes in the number and function of
      dendritic cells (DCs), which play a key role in the initiation of the immune
      response. This study aimed to dissociate effects of sleep and circadian rhythm on
      circulating numbers of DC precursors, ie, CD14+CD16- and CD14(dim)CD16+
      monocytes, myeloid dendritic cell precursors (pre-mDC), and plasmacytoid
      dendritic cells (PDC) and on 2 key cytokines produced by these cells, ie,
      interleukin (IL)-12 and interferon (IFN)-alpha. DESIGN: In a within-subject cross
      over design, human subjects were examined on 2 occasions, ie, during a normal
      sleep-wake cycle and during 24 hours of wakefulness. Blood was sampled every 1.5
      hours during nighttime and every 3 hours during daytime. SETTING: Experiments
      took place under controlled laboratory conditions. PARTICIPANTS: Twenty-seven
      healthy men aged between 18 and 30 years. MEASUREMENTS AND RESULTS: Compared with
      wakefulness, sleep was associated with a striking increase in the number of pre
      mDC producing IL-12, which is a main inducer of Th1 responses. In addition, sleep
      slightly decreased PDC and also T cell counts but did not affect IFN-alpha
      production by PDC. Sleep, however, substantially decreased numbers of
      CD14(dim)CD16+ monocytes, probably reflecting increased margination of the cells
      upon a sleep-related drop in catecholamine release. CONCLUSIONS: Our data
      identify pre-mDC producing IL-12 as a basic target of sleep that is most closely
      related to mature APC function and whereby sleep can effectively enhance adaptive
      immune responses.

PMID- 17520783
TI  - Interaction between sleep and the immune response in Drosophila: a role for the
      NFkappaB relish.
AB  - STUDY OBJECTIVES: The regulation of sleep is poorly understood. While some
      molecules, including those involved in inflammatory/immune responses, have been
      implicated in the control of sleep, their role in this process remains unclear.
      The Drosophila model for sleep provides a powerful system to identify and test
      the role of sleep-relevant molecules. DESIGN: We conducted an unbiased screen for
      molecular candidates involved in sleep regulation by analyzing genome-wide
      changes in gene expression associated with sleep deprivation in Drosophila. To
      further examine a role of immune-related genes identified in the screen, we
      performed molecular assays, analysis of sleep behavior in relevant mutant and
      transgenic flies, and quantitative analysis of the immune response following
      sleep deprivation. RESULTS: A major class of genes that increased expression with
      sleep deprivation was that involved in the immune response. We found that immune
      genes were also upregulated during baseline conditions in the cyc01 sleep mutant.
      Since the expression of an NFkappaB, Relish, a central player in the inflammatory
      response, was increased with all manipulations that reduced sleep, we focused on
      this gene. Flies deficient in, but not lacking, Relish expression exhibited
      reduced levels of nighttime sleep, supporting a role for Relish in the control of
      sleep. This mutant phenotype was rescued by expression of a Relish transgene in
      fat bodies, which are the major site of inflammatory responses in Drosophila.
      Finally, sleep deprivation also affected the immune response, such that flies
      deprived of sleep for several hours were more resistant to bacterial infection
      than those flies not deprived of sleep. CONCLUSION: These results demonstrate a
      conserved interaction between sleep and the immune system. Genetic manipulation
      of an immune component alters sleep, and likewise, acute sleep deprivation alters
      the immune response.

PMID- 17520785
TI  - Interleukin-1beta mediates sleep alteration in rats with rotenone-induced
      parkinsonism.
AB  - STUDY OBJECTIVE: Recently, the pathogenesis of Parkinson disease (PD) has been
      focused on microglial activation, especially the subsequent increase of
      cytokines. A body of clinical evidence suggests that sleep is altered in patients
      with PD; however, there is a lack of understanding of the basic cellular
      mechanism. This study was designed to elucidate the influence of brain
      interleukin (IL)-1beta on sleep changes, in addition to the dopaminergic and
      gamma-aminobutyric acid (GABA)-ergic systems, in an animal PD model. DESIGN: We
      employed a long-term subcutaneous infusion of rotenone, a mitochondrial complex-I
      inhibitor, to induce a parkinsonism-like model in rats. Behavioral tests and
      tyrosine hydroxylase immunocytochemistry were used for confirmation of PD in this
      animal model. Pharmacologic agonist and antagonists were administered centrally
      to test the involvement of dopamine, GABA, and IL-1 in rotenone-induced sleep
      alteration. Protein expression of cytokines, ie, IL-1beta and tumor necrosis
      factor alpha (TNF-alpha), in 5 distinct brain regions was also determined by
      Western blot and enzyme-linked immunosorbent assay (ELISA). SETTING: Sleep
      recording equipment in the National Taiwan University and China Medical
      University. PARTICIPANT AND INTERVENTIONS: Male Sprague-Dawley rats were
      implanted with electroencephalogram electrodes, a thermistor, and an
      intracerebroventricular guide cannula. Chronic infusion of rotenone was given by
      an Alzet minipump implanted subcutaneously on the back of each rat. MEASUREMENT
      AND RESULTS: We found that locomotion activity was reduced, slow-wave sleep (SWS)
      was increased during the dark (active) phase and decreased during the light
      (rest) period, and rapid eye movement sleep (REM) was enhanced in the dark period
      after rotenone treatment. This rotenone PD animal model successfully causes loss
      of tyrosine hydroxylase-immunopositive neurons in the substantia nigra; induces
      the events of sleep disturbance, such as excessive daytime sleepiness and
      insomnia during the nighttime, that are seen in patients with PD; and suppresses
      locomotion. Our results that intracerebroventricular administration of dopamine
      and blockade of GABA in the brain have less significant effect on rotenone
      induced sleep alteration suggest that the sleep disturbance is not primarily
      mediated by the disruption of dopaminergic and GABAergic systems in the current
      PD rat model. The expression of TNF-alpha was not altered by rotenone. However,
      the results of enhanced expression of IL-1beta in the hypothalamus after rotenone
      and that of the blockade of sleep alteration, but not the locomotion activity, by
      intracerebroventricular administration of an IL-1 receptor antagonist implies
      that increased IL-1beta in the hypothalamus mediates sleep alteration, but not
      the locomotion, in rats with rotenone-induced parkinsonism. CONCLUSION: These
      observations suggest that rotenone-induced sleep-wake alteration is dominated by
      central increase of somnogenic IL-1.

PMID- 17520786
TI  - Association between sleep and morning testosterone levels in older men.
AB  - STUDY OBJECTIVES: The circulating testosterone levels of healthy men decline with
      advancing age. This process is characterized by considerable inter-individual
      variability, the causes of which are of significant biological and clinical
      interest but remain poorly understood. Since sleep quantity and quality decrease
      with age, and experimentally-induced sleep loss in young adults results in
      hormonal changes similar to those that occur spontaneously in the course of
      aging, this study examined whether some of the variability in circulating
      testosterone levels of older men can be related to objective differences in their
      sleep. DESIGN: Observational study. SETTING: General community and university
      clinical research center. PARTICIPANTS: Twelve healthy men ages 64 to 74 years.
      INTERVENTIONS: Three morning blood samples were pooled for the measurement of
      total and free testosterone. In addition to overnight laboratory polysomnography,
      wrist activity monitoring for 6-9 days was used to determine the amount of
      nighttime sleep of the participants in everyday life settings. MEASUREMENTS AND
      RESULTS: The main outcome measures were total sleep time and morning testosterone
      levels. Sleep time in the laboratory was correlated with the usual amount of
      nighttime sleep at home (Pearson's r = 0.842; P = 0.001). Bivariate correlation
      and multiple linear regression analyses revealed that the amount of nighttime
      sleep measured by polysomnography was an independent predictor of the morning
      total (Beta 0.792, P = 0.017) and free (Beta 0.741, P = 0.029) testosterone
      levels of the subjects. CONCLUSIONS: Objectively measured differences in the
      amount of nighttime sleep are associated with a significant part of the
      variability in the morning testosterone levels of healthy older men.

PMID- 17520787
TI  - Hyperactive night and day? Actigraphy studies in adult ADHD: a baseline
      comparison and the effect of methylphenidate.
AB  - STUDY OBJECTIVES: To investigate parameters of sleep, activity, and circadian
      rhythm, as well as the effects of methylphenidate on these variables, in adults
      with ADHD. DESIGN: 1) Baseline group comparison; 2) Double blind, placebo
      controlled, cross-over medication trial. SETTING: Data collection took place
      during daily lives of participants. PARTICIPANTS: 39 normal controls and 33
      adults with ADHD for baseline comparisons; 31 adults with ADHD in medication
      trial. INTERVENTIONS: Treatment with placebo and methylphenidate during
      medication trial. MEASUREMENTS AND RESULTS: Actigraphy and sleep log data were
      collected for 7 consecutive nights and days to obtain baseline values for ADHD
      and normal controls. Repeated measurements during placebo and methylphenidate
      treatment were conducted for the ADHD group. Actigraphic sleep estimates showed
      that ADHD subjects took longer to fall asleep, had lower sleep efficiency, and
      had shorter within-night periods of uninterrupted sleep. These findings were
      consistent with subjective complaints. Actigraphic measures of ADHD subjects
      showed continuously elevated daytime activity levels, resulting in a 24-hour
      pattern that was more stable and less variable than in controls. Methylphenidate
      led to a later bedtime, later sleep onset, and reduction in sleep duration.
      However, number and total duration of nocturnal awakenings decreased, while mean
      duration of within-night periods of uninterrupted sleep increased, indicating
      more consolidated sleep. CONCLUSIONS: Our data suggest that sleep problems are
      inherent in adults with ADHD and that methylphenidate reduced total sleep time
      but improved sleep quality by consolidating sleep.

PMID- 17520788
TI  - Adipokines in children with sleep disordered breathing.
AB  - STUDY OBJECTIVE: Associations between SDB, the metabolic syndrome, and
      circulating levels of adipokines have emerged in adults but have not been
      examined in snoring children, who, in contradistinction to adults, display
      insulin resistance and lipid abnormalities as a function of adiposity rather than
      SDB. Therefore, we aimed to examine associations between circulating adipokines
      levels, insulin resistance, and measures of SDB in children. DESIGN: Prospective
      study. SETTING: Polysomnographic evaluation and assessment of plasma levels of
      leptin, adiponectin, resistin, glucose, insulin, and CRP. PARTICIPANTS: 130
      children (mean age 8.2 +/- 2.8 years; 39% obese) were studied. MEASUREMENTS AND
      RESULTS: Log adiponectin levels were lower in obese than nonobese children (3.8
      +/- 0.31 vs 4.0 +/- 0.30 corresponding to 8,381.4 +/- 5,841.0 vs 12,853.2 +/-
      7,780.2 ng/ml, P < 0.0001) and were inversely correlated with BMI Z scores (r = 
      0.47, P < 0.0001) but not with log AHI. Log leptin concentrations were higher in
      the obese group than the nonobese group (4.2 +/- 0.32 vs 3.4 +/- 0.57
      corresponding to 19,542.6 +/- 13,643.6 vs 5,875.5 +/- 8,425.7 pg/ml, P < 0.0001),
      correlated with BMI Z scores (r = 0.64, P < 0.0001), and were significantly lower
      in children with AHI < or = 1/hr than children with AHI > 1/hr (P = 0.006) and in
      children with SpO2 nadir > or = 90% than children with SpO2 nadir < 90%, even
      after controlling for BMI Z score (P < 0.03). No significant differences were
      found in log resistin levels as a function of obesity or AHI. Significant
      correlations between log adiponectin levels and log Insulin/Glucose (I/G) ratios
      (-0.28, P = 0.006) and between log leptin levels and log I/G ratios (r = 0.66, P
      < 0.0001) emerged. CONCLUSIONS: In close agreement with the absence of a
      measurable effect of SDB on insulin resistance in children, circulating
      adipokines levels are primarily attributable to the ponderal index. However, SDB
      and associated hypoxemia may contribute to the elevation of leptin levels.

PMID- 17520789
TI  - Reduced NREM sleep instability in children with sleep disordered breathing.
AB  - STUDY OBJECTIVES: To evaluate NREM sleep instability, as measured by the cyclic
      alternating pattern (CAP), in a cohort of children with mild sleep disordered
      breathing (SDB) or frank obstructive sleep apnea (OSA) and normal controls.
      DESIGN: Prospective study. SETTINGS: Sleep laboratory in academic center.
      PARTICIPANTS: Twenty-two patients (13 boys; mean age 6.5 +/- 2.4 years; 10 with
      mild SDB and 12 with OSA) and 15 normal children matched for age underwent
      overnight polysomnographic recordings in a standard laboratory setting. Sleep was
      visually scored for sleep macrostructure and CAP in a blinded fashion using
      standard criteria. Markovian analysis was also performed. MEASUREMENTS AND
      RESULTS: Participants with OSA had reduced total CAP rates than normal controls
      and mild SDB patients. Children with mild SDB or OSA had a lower number of A1,
      lower A1 percentage, and lower A1 index than controls. Children with OSA also
      showed longer intervals between consecutive A phases and a decrease in entropy in
      the Markovian analysis. CONCLUSIONS: The lower CAP rate and its reduced entropy
      in children with mild SDB or OSA seem to indicate the presence of subtle sleep
      alterations that are not clearly identifiable with other approaches and might
      provide more robust correlates of neurocognitive and behavioral dysfunction in
      snoring children.

PMID- 17520790
TI  - Redefining success in airway surgery for obstructive sleep apnea: a meta analysis
      and synthesis of the evidence.
AB  - STUDY OBJECTIVES: The role of upper airway surgery as a treatment for adult
      obstructive sleep apnea (OSA) remains controversial, with perspectives on
      treatment efficacy varying considerably. Though debate may occur in the clinical
      sphere, it is necessary to appreciate the ever-increasing funding and policy
      focus on cost effectiveness and "efficacy" in health care. DESIGN: In this
      review, we examine contemporary evidence that highlights the importance of
      "highly effective treatment" over "sub-therapeutic treatment" as a necessity to
      confer improved health outcomes in OSA. We highlight that assumptions of surgical
      success inherent in most articles fail to assimilate contemporary, clinically
      significant indicators of success. We performed a literature search and present
      interpolated meta-analyses data from 18 surgical articles. Statistical meta
      analyses highlight how surgical success decreases when new evidence-based
      criteria of success are applied. MEASUREMENTS AND RESULTS: Specifically, when the
      traditional definition is applied (50% reduction in apnea-hypopnea index [AHI]
      and/or < or = 20) the pooled success rate for Phase I procedures is 55% (45%
      fail). However, at AHI < or = 10, success reduces to 31.5% (68.5% fail) and, at
      AHI < or = 5, success is reduced to 13% (87% fail). According to these
      definitions, Phase II success (fail) rates decrease from 86% (14%) to 45% (55%)
      and 43% (57%), respectively. CONCLUSIONS: The evidence for clinical efficacy must
      define treatment "success". We propose all future surgical audits report
      "objective cure" rates with success based on AHI outcomes of < or = 5 and/or < or
      = 10. We hope this paper serves as a catalyst for debate and consensus.

PMID- 17520791
TI  - Adaptive servoventilation versus noninvasive positive pressure ventilation for
      central, mixed, and complex sleep apnea syndromes.
AB  - RATIONALE: Although continuous positive airway pressure (CPAP) is most often
      effective in patients with obstructive sleep apnea, optimal treatment of patients
      with predominantly mixed apneas, central sleep apnea syndrome/Cheyne-Stokes
      respiration (CSA/CSR), or complex sleep apnea (CompSAS) is less straightforward,
      and may require alternative ventilatory assist modalities. OBJECTIVES: To compare
      the efficacy of noninvasive positive pressure ventilation (NPPV) with adaptive
      servoventilation (ASV) in treating patients with centrally mediated breathing
      abnormalities. We hypothesized that NPPV and ASV would be equivalently
      efficacious in improving the apnea/hypopnea index (AHI) and respiratory arousal
      index (RAI). METHODS: Prospective randomized crossover clinical trial comparing
      NPPV with ASV in patients with CSA/CSR, predominantly mixed apneas, and CompSAS
      in an acute setting. MEASUREMENTS AND MAIN RESULTS: 21 patients (6 with CSA/CSR,
      6 with predominantly mixed apneas, and 9 with CompSAS) with initial diagnostic
      AHI +/- standard deviation 51.9 +/- 22.8/hr and RAI 45.5 < or = 26.5/hr completed
      the study. Following optimal titration with CPAP (N = 15), disturbed breathing
      and disturbed sleep remained high with mean AHI = 34.3 +/- 25.7 and RAI = 32.1 +/
      29.7. AHI and RAI were markedly reduced with both NPPV (6.2 +/- 7.6 and 6.4 +/-
      8.2) and ASV (0.8 +/- 2.4 and 2.4 +/- 4.5). Treatment AHI and RAI were both
      significantly lower using ASV (P < 0.01). CONCLUSION: These data confirm that in
      patients with CSA/CSR, mixed apneas, and CompSAS, both NPPV and ASV are effective
      in normalizing breathing and sleep parameters, and that ASV does so more
      effectively than NPPV in these types of patients.

PMID- 17520792
TI  - Pentobarbital sedation increases genioglossus respiratory activity in sleeping
      rats.
AB  - OBJECTIVE: To determine whether certain sedatives may, by increasing arousal
      threshold, allow pharyngeal dilator muscle activity to increase more in response
      to chemical stimuli before arousal occurs. DESIGN, PARTICIPANTS AND
      INTERVENTIONS: Thirteen chronically instrumented rats were studied during sleep
      following injections of placebo or sedating doses of pentobarbital (10 mg/kg).
      Intermittently, inspired CO2 was increased gradually until arousal occurred.
      MEASUREMENTS AND RESULTS: Maximum genioglossus activity reached before arousal
      was higher with pentobarbital than placebo (34.5 +/- 24.3 vs 3.7 +/- 2.9mV; P <
      0.001) for 2 reasons. First, genioglossus activity was greater during undisturbed
      sleep before CO2 was applied (23.3 +/- 15.3 vs 2.5 +/- 1.5 mV, P < 0.001). When
      sleep periods were long, a ramp-like increase in genioglossus activity (GG-Ramp)
      began and progressed until arousal. GG-Ramps developed with both placebo and
      pentobarbital but reached higher levels with pentobarbital due to longer sleep
      periods and faster increase in genioglossus activity during the ramp. GG-Ramps
      began when diaphragm activity was lowest and progressed despite unchanged
      diaphragm activity. Second, as hypothesized, the increase in genioglossus
      activity with CO2 before arousal was greater than with placebo (11.2 +/- 2.5 vs
      1.2 +/- 2.5mV; P < 0.05) due to increased arousal threshold. In 27 of 126 CO2
      challenges delivered while GG-Ramps were in progress, genioglossus activity
      paradoxically decreased despite increased diaphragmatic activity. These negative
      responses occurred randomly in 7 of 13 rats. CONCLUSIONS: In rats: 1) Sedatives
      may allow genioglossus activity to reach higher levels during sleep. 2) A time
      dependent increase in genioglossus activity occurs during undisturbed sleep that
      is unrelated to chemical drive. 3) Transient hypercapnia may elicit inhibition of
      genioglossus activity under currently unidentified circumstances.

PMID- 17520793
TI  - Auditory startle reaction is disinhibited in idiopathic restless legs syndrome.
AB  - STUDY OBJECTIVES: Because the auditory startle reaction is abnormal in disorders
      with substantia nigra pathology, we hypothesized that auditory startle responses
      (ASRs) might also be altered in restless legs syndrome (RLS). DESIGN:
      Neurophysiologic study of the auditory startle reaction. SETTING: Neurology
      departments of a university hospital and an affiliated local hospital. PATIENTS
      AND PARTICIPANTS: Fifteen patients with idiopathic RLS (6 de novo, 9 untreated
      after a 7-day wash-out period of levodopa, mean duration of RLS [corrected]
      symptoms 21.2 +/- 17.9 years, mean IRLS [corrected] severity score 23.5 +/- 6.7)
      and 15 sex- and age-matched healthy controls were investigated. INTERVENTIONS:
      Not applicable. MEASUREMENTS AND RESULTS: ASRs were elicited by 8 high-intensity
      auditory stimuli differing randomly in tonal frequency and intensity. Reflex
      electromyographic activity was simultaneously recorded with surface electrodes
      from 8 facial, neck, arm, and leg muscles. In RLS patients, ASRs were
      significantly more frequent (541 of 960 possible responses; controls, 430 of
      960), and ASR area under the curve was significantly larger (3812 +/- 450
      microVms; controls, 1756 +/- 226 microVms). Analysis per body region revealed
      that ASRs were significantly more frequent in RLS patients than in controls in
      leg muscles (138/360 vs 55/360); ASR latencies to leg muscles were significantly
      shorter in RLS patients (129 +/- 6 ms vs 160 +/- 11 ms); ASR area under the curve
      was significantly larger in RLS patients in facial (7547 +/- 1326 mmicroVms vs
      2982 +/- 448 microVms) and leg muscles (1373 +/- 308 microVms vs 541 +/- 193
      microVms). CONCLUSIONS: Our data demonstrate disinhibition of reticulospinal
      pathways in RLS patients as compared to normal controls, likely originating from
      dysfunction rostral to the lower brainstem.

PMID- 17520794
TI  - The effects of sleep deprivation on pain inhibition and spontaneous pain in
      women.
AB  - Impaired central pain modulation is implicated in the pathophysiology of chronic
      pain. In this controlled experiment, we evaluated whether partial sleep loss
      altered endogenous pain inhibition and reports of spontaneous pain. Thirty-two
      healthy females were studied polysomnographically for 7 nights. On Nights 1-2
      (Baseline), subjects slept undisturbed for 8 hours. After Night 2, subjects were
      randomized to Control (N = 12), Forced Awakening (FA, N = 10), or Restricted
      Sleep Opportunity (RSO, N = 10) conditions. Controls continued to sleep
      undisturbed. FA underwent 8 forced awakenings (one per hour) on Nights 3-5. RSO
      subjects were yoked to FA on total sleep time (TST), receiving partial sleep
      deprivation by delayed bedtime. On Night 6, both FA & RSO underwent 36 hours
      total sleep deprivation (TSD), followed by 11-hour recovery sleep (Night 7).
      Subjects completed twice-daily psychophysical assessments of mechanical pain
      thresholds and pain inhibition (Diffuse Noxious Inhibitory Controls), via use of
      a conditioning stimulus (i.e., cold pressor) paradigm. FA and RSO demonstrated
      50% reductions in total sleep time and increases in nonpainful somatic symptoms
      during partial sleep deprivation. While sleep deprivation had no effect on pain
      thresholds, during partial sleep deprivation the FA group demonstrated a
      significant loss of pain inhibition and an increase in spontaneous pain; neither
      of the other 2 groups showed changes in pain inhibition or spontaneous pain
      during partial sleep deprivation. These data suggest that sleep continuity
      disturbance, but not simple sleep restriction, impairs endogenous pain-inhibitory
      function and increases spontaneous pain, supporting a possible pathophysiologic
      role of sleep disturbance in chronic pain.

PMID- 17520795
TI  - Arousal responses to olfactory or trigeminal stimulation during sleep.
AB  - STUDY OBJECTIVES: The interaction of sensory physiology and sleep has been
      studied for various sensory systems. Nevertheless, the question whether
      chemosensory (especially olfactory) stimuli may lead to arousals during sleep
      remains under discussion. Specifically, the central processing of olfactory
      information shows fundamental differences compared to other sensory systems.
      DESIGN: Prospective controlled trial. SETTING: Sleep research facility,
      University Hospital. PARTICIPANTS: Five young healthy, normosmic volunteers.
      INTERVENTION: Intranasal chemosensory stimulation during sleep was based on air
      dilution olfactometry. For olfactory stimulation H2S (smell of rotten eggs) was
      used in 4 concentrations (1, 2, 4, and 8 ppm). For trigeminal stimulation CO2
      (stinging sensation) was also administered in 4 concentrations (10%, 20%, 40%,
      and 60% v/v) while odorless stimuli were used for control. MEASUREMENTS: Arousal
      reactions due to chemosensory stimulation were assessed during overnight
      polysomnography 30 seconds after the presentation of every stimulus during 23
      nights of testing. RESULTS: For olfactory testing, an average number of 703
      olfactory stimuli and 157 odorless controls were used for analysis per subject.
      Even the highest stimulus concentration did not produce an increase in arousal
      frequency. For trigeminal testing, an average number of 405 stimuli and 79
      controls were used for analysis per subject, and an increase in arousal frequency
      was observed following the increase of stimulus concentration. CONCLUSIONS: With
      the present results we were able to demonstrate that, in contrast to trigeminal
      stimulation, the presentation of a strong but selective olfactory stimulus does
      not lead to arousals during nocturnal sleep in humans.

PMID- 17520796
TI  - Sensory stimulation triggers spindles during sleep stage 2.
AB  - STUDY OBJECTIVES: Toward understanding the function of sleep spindle, we examined
      whether sensory stimulation triggers sleep spindles. PARTICIPANTS: Eleven normal
      subjects participated in the experiments. INTERVENTION: The subjects had a nap in
      the afternoon, and sensory stimulation was applied during sleep stage 2.
      MEASUREMENTS: 21-channel EEG was recorded during the 2-3 hour experiment carried
      out between 13:00 and 16:00. Somatosensory, auditory, or visual stimulation was
      performed over a 5-minute period during stage 2. The frequency and duration of
      spindles were compared in 2 different segments of 5 minutes, with and without
      sensory stimulation. The latency from the onset of a sensory stimulus to the
      succeeding spindle was also analyzed. To estimate the active brain regions during
      a spindle, the EEG recordings were modeled with a single equivalent moving dipole
      (SEMD) model. RESULTS: In the period with stimulation, spindle frequency and
      duration increased compared with the period without stimulation. Statistical
      tests revealed that with stimulation, the interval between 2 consecutive spindles
      was significantly shorter (p < 0.05, regardless of the modality) and that the
      duration of the spindles was significantly longer with stimulation (p < 0.05,
      regardless of the modality). The latency was approximately 2 s. During a spindle
      after somatosensory stimulation brain activities were observed near the
      somatosensory area, while with auditory stimulation active regions were observed
      near the auditory cortex. CONCLUSIONS: A sensory stimulus appeared to trigger a
      sleep spindle during sleep stage 2. SEMD trajectories suggest that active brain
      regions during spindle are different according to the modality of the preceding
      stimulus.

PMID- 17520797
TI  - Practice parameters for the use of actigraphy in the assessment of sleep and
      sleep disorders: an update for 2007.
AB  - BACKGROUND: Actigraphy is increasingly used in sleep research and the clinical
      care of patients with sleep and circadian rhythm abnormalities. The following
      practice parameters update the previous practice parameters published in 2003 for
      the use of actigraphy in the study of sleep and circadian rhythms. METHODS: Based
      upon a systematic grading of evidence, members of the Standards of Practice
      Committee, including those with expertise in the use of actigraphy, developed
      these practice parameters as a guide to the appropriate use of actigraphy, both
      as a diagnostic tool in the evaluation of sleep disorders and as an outcome
      measure of treatment efficacy in clinical settings with appropriate patient
      populations. RECOMMENDATIONS: Actigraphy provides an acceptably accurate estimate
      of sleep patterns in normal, healthy adult populations and inpatients suspected
      of certain sleep disorders. More specifically, actigraphy is indicated to assist
      in the evaluation of patients with advanced sleep phase syndrome (ASPS), delayed
      sleep phase syndrome (DSPS), and shift work disorder. Additionally, there is some
      evidence to support the use of actigraphy in the evaluation of patients suspected
      of jet lag disorder and non-24hr sleep/wake syndrome (including that associated
      with blindness). When polysomnography is not available, actigraphy is indicated
      to estimate total sleep time in patients with obstructive sleep apnea. In
      patients with insomnia and hypersomnia, there is evidence to support the use of
      actigraphy in the characterization of circadian rhythms and sleep
      patterns/disturbances. In assessing response to therapy, actigraphy has proven
      useful as an outcome measure in patients with circadian rhythm disorders and
      insomnia. In older adults (including older nursing home residents), in whom
      traditional sleep monitoring can be difficult, actigraphy is indicated for
      characterizing sleep and circadian patterns and to document treatment responses.
      Similarly, in normal infants and children, as well as special pediatric
      populations, actigraphy has proven useful for delineating sleep patterns and
      documenting treatment responses. CONCLUSIONS: Recent research utilizing
      actigraphy in the assessment and management of sleep disorders has allowed the
      development of evidence-based recommendations for the use of actigraphy in the
      clinical setting. Additional research is warranted to further refine and broaden
      its clinical value.

PMID- 17520798
TI  - The association of angiotensin converting enzyme (ACE) polymorphisms with sleep
      apnea and hypertension.
AB  - STUDY OBJECTIVES: To identify the role of polymorphisms in the angiotensin
      converting enzyme (ACE) gene in modulating susceptibility to hypertension in
      sleep apnea. DESIGN: Observational cross-sectional study. PARTICIPANTS: Nine
      hundred seventy-two participants of the Cleveland Family Study who underwent home
      sleep studies, blood pressure assessments, and genotyping. RESULTS: After
      controlling for age, sex, race, and obesity, hypertension risk was reduced in
      participants who possess the ACE deletion (D) polymorphism with an odds ratio =
      0.63 (95% confidence interval: 0.41-0.96) comparing those with 2 versus no D
      alleles. In analyses stratified by apnea severity, the protective effect of the D
      allele was most evident in those with severe apnea. Among subjects with severe
      apnea, the odds ratios for hypertension were 0.47 (0.22-1.00) for 1 D allele and
      0.57 (0.26-1.24) for 2 D alleles. CONCLUSIONS: The ACE deletion allele may
      protect against hypertension in the setting of obstructive sleep apnea. Further
      research into the potential role of angiotensin in modulating the hypertensive
      effect of sleep apnea is needed.

PMID- 17520799
TI  - Recent advances in the preparation progress of protein/peptide drug loaded
      PLA/PLGA microspheres.
AB  - Sustained release drug delivery from microparticles is an excellent alternative
      for daily protein/peptide drug administration protocol. Poly(lactic acid) (PLA)
      and poly(lactic-co-glycolic acid) (PLGA) are the most commonly used polymer
      carriers in the development of protein/peptide microspheres. Basically there are
      three preparation methods for PLA/PLGA microspheres: the solvent
      extraction/evaporation based multiple emulsion (W/O/W emulsion) method, the phase
      separation method and the spray drying method. The stability of the
      protein/pipetide loaded, encapsulation efficiency, and the burst effect of the
      microspheres are key problems usually met in the preparation of microspheres. In
      this review the preparation techniques and progress in the development of
      protein/pipetide microspheres which aimed to stabilize protein/peptide structural
      integrity, keep the bioactivity of drugs, increase the encapsulation efficiency
      and improve the release profile were summarized and evaluated.

PMID- 17520800
TI  - [Effects of the flavonoids on cytochrome P-450 CYP1, 2E1, 3A4 and 19].
AB  - Flavonoids are present in fruits, vegetables and beverages derived from plants,
      and in many dietary supplements or herbal remedies. A number of naturally
      occurring flavonoids have been shown to modulate the CYP450 system, including the
      induction or inhibition of these enzymes. This review focuses on the flavonoid
      effects on cytochrome P450 (CYP) enzyme CYP1, 2E1, 3A4 and 19. Flavonoids alter
      CYPs by various mechanisms, including the stimulation of gene expression via
      specific receptors and/or CYP protein, or mRNA stabilization and so on. But in
      vivo and in vitro, the effects of flavonoids are not always coincident as a
      result of concentrations of flavonoids, genetic and environmental factors. As
      well, flavonoids may interact with drugs through the induction or inhibition of
      their metabolism. Much attention should be paid to the metabolism interaction of
      the flavonoids when coadministered with other drugs.

PMID- 17520801
TI  - [A new method for quantitative assessment of mechanisms of partitioning and
      absorption of drugs: linear solvation energy relationships].
AB  - Linear solvation energy relationships are of a great value in investigating
      quantitative structure-retention relationship and quantitative structure-activity
      relationship, and predicting chromatographic retention indices of drugs. Several
      quantitative relationships in different in vitro biomembrane-mimetic models
      between retention factors and molecular descriptors have been established
      successfully and used to clarify drug-membrane interaction mechanisms.
      Quantitative structure-activity relationships also have been established to
      predict drug intestinal absorption, permeation of skin and blood-brain barrier.
      This review focused on the significance and widely application of linear
      solvation energy relationships in quantitative assessment for mechanisms of
      partitioning and absorption of drugs. The discrepancy and limits of linear
      solvation energy relationships were also discussed, which gives us a better
      insight into investigation of partitioning and absorption of drugs.

PMID- 17520802
TI  - [Resveratrol restored the structural and functional association between M3
      receptor and connexin 43 gap junction proteins in ischemia-reperfusion injury of
      isolated rat heart].
AB  - This study is to explore whether the protective effect of resveratrol on ischemia
      reperfusion injury is correlated with the structural and functional association
      between M3 receptor (M3 subtype of muscarinic acetylcholine receptor) and Cx43
      (connexin 43 gap junction proteins). Immunoprecipitation, immunoblotting and
      immunofluorescence were applied to investigate whether resveratrol has an effect
      on structural and functional association between M3 and Cx43. The effect of
      resveratrol on electrocardiogram Lead II ex vivo in rats, SOD (superoxide
      dismutase) activity and MDA (malondialdehyde) content was also observed in order
      to evaluate the protective effect of resveratrol on ischemia-reperfusion injury.
      Resveratrol could restore the structural and functional association between M3
      receptor and Cx43 gap junction proteins that was partially destroyed under
      ischemia-reperfusion injury. The phosphorylation and spatial distribution
      disturbances in Cx43 expression caused by ischemia-reperfusion injury were also
      restored. Also, the QRS duration, SOD activity and MDA content were restored.
      Resveratrol could restore the structural and functional association between M3
      receptor and Cx43 gap junction proteins.

PMID- 17520803
TI  - [Effect of ZGDHu-1 on proliferation and apoptosis of A549 cells in vitro and
      antitumor activity in vivo].
AB  - This study is to explore the mechanism and effect of N, N'-di-(m-methylphenyl)-3,
      6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide (ZGDHu-1) on
      proliferation and apoptosis of A549 cells in vitro and on A549 xenograft tumor in
      nude mice. With different concentrations of ZGDHu-1 at different times were used
      to treat A549 cells in vitro. The proliferation was determined by living cell
      count, SRB assay and Brdu-ELISA. Cell apoptosis was determined by cell
      morphology, DNA agarose gel electrophoresis, DNA content, Annexin V/PI and
      Hoechst 33258 labeling method. The nude mice model of A549 xenograft tumor was
      established by subcutaneous inoculation. The suppression activity of ZGDHu-1 by
      intraperitoneal injection on xenograft mice model was detected. The expressions
      of bcl-2, bax and p53 gene and protein were analyzed by RT-PCR and flow
      cytometry. ZGDHu-1 can inhibit A549 cell proliferation viability within a certain
      range of treating time and does, and a majority of A549 cells were arrested in G2
      M phase. The A549 cells apoptosis was confirmed by typical cell morphology, DNA
      fragment, Sub G1 phase, Hoechst 33258 and Annexin V/PI labeling method with a
      time and dose related manner. When the xenograft tumor mice model were treated
      with 10, 20 and 40 mg x kg(-1) ZGDHu-1 for 14 days, the tumor growth inhibition
      rate were 43.7%, 56.9% and 60.0%, respectively. The expression of bax, bax/bcl-2
      and p53 gene and protein increased significantly and bcl-2 decreased slightly by
      the treatment of ZGDHu-1. ZGDHu-1 can significantly suppress the growth of A549
      xenograft tumor in vivo and inhibited proliferation by inducing tumor cell
      apoptosis in vitro. The mechanism may associate with its up-regulation of bax and
      p53 during the apoptosis process.

PMID- 17520804
TI  - [Mechanism of downregulation of apoptosis by autophagy induced by oridonin in
      HeLa cells].
AB  - To study the mechanism of downregulation of apoptosis by autophagy induced by
      oridonin in HeLa cells, the cell viability was measured by MTT method. DNA
      fragmentation was assayed by agarose gel electrophoresis. Autophagic and
      apoptotic ratio was determined by flowcytometric analysis. Protein expression was
      detected by Western blotting analysis. Oridonin induced both apoptosis and
      autophagy in HeLa cells. Apoptosis was upregulated by introduction of the
      inhibitor of autophagy, 3-methyladenine (3-MA). Addition of oridonin increased
      Bax/Bcl-2 expression ratio and cytochrome c, whereas the expression of SIRT-1 was
      decreased, and 3-MA pre-application enhanced these changes. Oridonin-induced
      autophagy antagonized apoptosis in HeLa cells through mitochondrial pathway.

PMID- 17520805
TI  - [A new SVRDF 3D-descriptor of amino acids and its application to peptide
      quantitative structure activity relationship].
AB  - To establish a new amino acid structure descriptor that can be applied to
      polypeptide quantitative structure activity relationship (QSAR) studies, a new
      descriptor, SVRDF, was derived from a principal components analysis of a matrix
      of 150 radial distribution function index of amino acids. The scale was then
      applied in three panels of peptide QSAR that were molded by partial least squares
      regression. The obtained models with the correlation coefficients (R2(cum)),
      cross-validation correlation coefficients (Q2(cum)) were 0.766 and 0.724 for 48
      bitter tasting dipeptides; 0.941 and 0.811 for 21 oxytocin analogues; 0.996 and
      0.919 for 20 thromboplastin inhibitors. Satisfactory results showed that
      information related to biological activity can be systemically expressed by SVRDF
      scales, which may be an useful structural expression methodology for the study of
      peptides QSAR.

PMID- 17520806
TI  - Identification of novel inhibitors of the streptogramin group A acetyltransferase
      via virtual screening.
AB  - Virginiamycin acetyltransferase D (VatD) plays a vital rule in streptogramins
      resistance by chemically inactivating streptogramin A. Therefore, it is desirable
      to discover novel small molecular weight inhibitors of VatD via state-of-the-art
      virtual screening techniques. This "cocktail" strategy by combining VatD
      inhibitor with streptogramins may provide new therapeutic opportunity for
      resistant bacteria infections. Structure-based virtual screening method
      (molecular docking) was applied to rank and score a chemical database containing
      300 000 commercially available compounds against the VatD substrate binding site.
      Twenty six out of the 200 top scored compounds from the docking calculation were
      selected and submitted to the VatD enzymatic inhibition assay. The plasmid pRSET
      B/vatD was constructed and transformed into E. coli (trxB) host cells for over
      expression, and VatD enzyme was purified and validated by showing
      acetyltransferase activity to Virginiamycin M1. Three out of these 26 tested
      compounds showed enzymatic inhibition on VatD with IC50 168.6, 91.0 and 55.2
      micromol x L(-1), separately. Other compounds could not be dissolved in the
      system and/or had little effect on the enzyme (IC50 > 200 micromol x L(-1)). To
      our knowledge, it is first time that small molecular weight organic compounds
      were identified as VatD inhibitors. It is expected that the VatD inhibitors
      identified at present study could serve as lead compounds for the further
      development of the novel therapeutic agents to overcome streptogramins
      resistance.

PMID- 17520807
TI  - [Synthesis and antibacterial activity of 3-(4-piperazin-1-yl-phenyl)-s-triazolo
      [3,4-b] [1,3,4] thiadiazole hydrochlorides].
AB  - To study the synthetic method and antibacterial activity of water-soluble fused
      heterocyclic compounds containing piperazine group, the nucleophilic substitution
      of 3-(4-chlorophenyl)-6-substituted-s-triazolo-[3, 4-b] [1, 3, 4] thiadiazoles
      (2a - n) with piperazine in the presence of phase transfer catalyst TBAI afforded
      3-(4-piperazin-1-yl-phenyl)-6-substituted-s-triazolo [3, 4-b] [1, 3, 4]
      thiadiazole and then followed by acid treatment afforded 3-(4-piperazin-1-yl
      phenyl)-6-substituted-s-triazolo [ 3, 4-b] [1, 3, 4] thiadiazole hydrochlorides
      (3a - n). Twenty-eight new compounds were synthesized and their structures were
      confirmed by IR, 1H NMR, MS and element analysis. The in vitro antibacterial
      activities of all newly synthesized compounds were tested against Gram positive
      bacteria and Gram negative bacteria with the standard 2-fold agar dilution
      method. Fourteen title compounds exhibited potential antibacterial activities in
      vitro. The structures of these compounds needed to be further optimized.

PMID- 17520808
TI  - A new diterpenoid from Fritillaria anhuiensis.
AB  - The aim of this study was to look for the chemical constituents of the bulbs of
      Fritillaria anhuiensis S. C. Chen et S. E. Yin. The bulbs of Fritillaria
      anhuiensis were extracted with 95% EtOH at reflux. Isolation and purification
      were performed by silica gel column chromatography. Structures of pure compounds
      were established on the basis of spectral analysis. Three compounds were obtained
      and identified as 12,15-epoxy-8(17), 13-labdadien-19-ol (1), ent-3beta-acetoxy
      kauran-16beta, 17-diol (2), ent-kaurane-3beta, 16beta, 17-triol (3). Compound 1
      is a new labdane-type diterpenoid. Compounds 2 and 3 were obtained from
      Fritillaria anhuiensis for the first time.

PMID- 17520809
TI  - [Pharmacokinetics of triptolide in Beagle dogs].
AB  - The aim of this paper is to develop and validate a rapid and sensitive LC-APCI/MS
      method for the determination of triptolide (TP) in plasma and to study the
      pharmacokinetic properties of TP in Beagle dogs. Sample preparation consisted of
      liquid-liquid extraction of interests. with ethyl acetate from dog plasma. The
      analytes and internal standard prednisolone were well separated on a Zorbax
      Extend-C18 analytical column. Plasma TP was detected by selected-ion monitoring
      (SIM) of LC-APCI/MS as its deprotonated molecular ions [M - H] - at m/z 358.9.
      Pharmacokinetic studies were undertaken in dogs following an iv dose of 0.05 mg x
      kg(-1) of TP or an ig dose of 0.05, 0.08, 0.1 mg x kg(-1), separately. The
      pharmacokinetic parameters were calculated by DAS software. Calibration curves
      were linear over the concentration range of 1 - 200 ng x mL(-1) of TP with the
      within- and between-batch precisions less than 10%. The within and between-batch
      accuracy was 95.0% to 105.0%. Recovery of LC-MS method for TP in plasma was over
      75%. The T1/2beta was (2.5 +/- 0.8) h after intravenous administration of TP at
      the dose of 0.05 mg x kg(-1). There were no significant differences in T(max),
      T1/2 alpha and T1/2 beta among the three ig dosage groups. AUC and C(max)
      increased proportionally with doses. The absolute bioavailability of TP after ig
      administration of 0.05 mg x kg(-1) was (75 +/- 17)%. The LC-MS method for
      determination of triptolide in dog plasma was sensitive and rapid. It was showed
      that the elimination of triptolide was rapid. The absolute bioavailability of
      triptolide given orally was high.

PMID- 17520810
TI  - [Pharmacokinetics and distribution of 5-Fu magnetic albumin deuto-microsphere in
      normal and tumor-bearing mice].
AB  - To observe the pharmacokinetic and tissue-distribution characters of 5
      flourouracil magnetic albumin deuto-microsphere (5-Fu-MAD) in normal and tumor
      bearing mice, HPLC method for the determination of 5-Fu in plasma and tissues was
      established and applied to determine 5-Fu in mouse plasma and tissue samples. A
      Flame atomic absorption spectrometer was used to detect the iron concentration in
      mouse tissue. Plasma concentration-time curves of free 5-Fu, 5-Fu-MAD and 5-Fu
      MAD plus the magnetic frame (MF) conformed to two compartment model of first
      order absorption and they had C(max) of 34.9, 7.95 and 5.97 mg x L(-1); T1/2 (Ke)
      of 22.26, 76.0 and 124.6 min, V(d) of 3.28, 30.7 and 66.1 L x kg; AUC(0-t), of
      233.9, 78.3 and 50.2 mg x min x L(-1); AUC(0-infinity) of 237.2, 89.3 and 68.1 mg
      x min x L(-1), respectively. The distribution of 5-Fu and iron was the highest in
      the plenty blood perfusion organs like the liver, tumor, spleen and lung, while
      lower in the kidney and heart and lowest in brain and muscle. The tissue
      distribution of muscle and tumor increased significantly when a magnetic frame
      was inserted there. The pharmacokinetics and tissue distribution of 5-Fu-MAD
      exhibited sustained-release and target characteristics.

PMID- 17520811
TI  - [HPLC fingerprinting of radix paeoniae alba].
AB  - To establish a sensitive and specific HPLC method for quality control of Radix
      Paeoniae Alba, HPLC method was applied for quality assessment of Radix Paeoniae
      Alba. HPLC analysis was performed on a Symmetry C18 column (250 mm x 4. 6 mm ID,
      5 microm, Waters, USA). The mobile phase consisted of acetonitrile (solvent A)
      and water containing 0.1% (v/v) phosphoric acid (solvent B) at a constant flow
      rate of 0.8 mL x min(-1). An increasing linear gradient (v/v) of solvent A was
      used (t/min, % A): (0,10), (5,10), (25,15), (45, 22), (46, 65), (50, 80) and (60,
      80). The column temperature was set at 25 degrees C. The chromatograms were
      monitored at 230 nm and the on-line UV spectra were recorded in the range of 190 
      400 nm. The HPLC chromatographic fingerprinting of Radix Paeoniae Alba, showing
      11 characteristic peaks, was established from 28 lots of Radix Paeoniae Alba. The
      areas of main chromatographic peaks were found to complied with the following
      rule: paeoniflorin > 1, 2, 3, 4, 6-penta-O-galloyl-glucos > albiflorin > methyl
      gallate > other compounds. The chromatographic fingerprinting of Radix Paeoniae
      Alba with high specificity can be used to control its quality and assure lot-to
      lot consistency.

PMID- 17520812
TI  - [Comparison between the qualitative similarity and the quantitative similarity of
      chromatographic fingerprints of traditional Chinese medicines].
AB  - To explore the differences between the qualitative similarity and the
      quantitative similarity of chromatographic fingerprints of traditional Chinese
      medicines, the quantitative similarity calculated by vector shadow C%, apparent
      quantitative similarity R%, quantitative similarity P%, etc. were firstly
      proposed to disclose the quantitative information characteristics of traditional
      Chinese medicines fingerprints. The HPLC fingerprints of both the standard
      Fructus gardeniae and the ten batches of Fructus gardeniae produced in different
      places were evaluated by the new parameters to obtain good results. The
      contrasted fingerprint contained 35 peaks while geniposide was selected as the
      reference peak. The HPLC fingerprint had good precision and reproducibility with
      the RSD of the relative retention time less than 1.5% and the RSD of the relative
      peak area within 5%. The qualitative similarity and quantitative similarity
      between each crude drug and the contrasted fingerprint were quantitatively
      calculated, the values of C%, P%, etc., were applied in the quality control
      practice, which had less errors. What is more, this method could be used for the
      overall quality control of Fructus gardeniae and especially suits for qualitative
      and quantitative evaluations of the chromatographic fingerprints both in chemical
      constituent distribution and in contents. The quantitative parameters such as C%
      and P% can be used to objectively, authentically and thoroughly display the
      content information characteristics. When they combined with the qualitative
      similarity, it will be the good method to evaluate the chromatographic
      fingerprints of traditional Chinese medicines.

PMID- 17520813
TI  - [Surface-modified paclitaxel-loaded nanoparticles as local delivery system for
      the prevention of vessel restenosis].
AB  - The novel paclitaxel-loaded nanopaticle through surface modification with
      didodecylmethylammonium bromide (DMAB) was prepared and its prevenative against
      neointimal formation in a rabbit carotid artery injury model was tested.
      Paclitaxel-loaded nanoparticles were prepared from oil-water emulsions using
      biodegradable poly (lactic acid-co-glycolic acid) (PLGA). Specific additive for
      surface conjugation was added after particle formation. To enhance arterial
      retention using a cationic surfactant, DMAB, was used. The size and distribution,
      surface morphology and surface charge of the paclitaxel-loaded nanoparticles were
      then investigated by laser light scattering, scanning electron microscope and
      zeta potential analyzer. The drug encapsulation efficiency (EE) and in vitro
      release profile were measured by high-performance liquid chromatography (HPLC).
      Balloon injured rabbit carotid arteries were treated with single infusion of the
      paclitaxel-loaded NP suspension and observed for 28 days. The inhibitory effects
      of vascular smooth muscle cell migration and proliferation were evaluated as end
      point. The NPs showed spherical shape with diameter ranging from 200 to 500 nm.
      The negatively charged PLGA NPs shifted to positive after the DMAB modification.
      The in vitro drug release profile showed a triphasic release pattern. 28 days
      later, morphologic analysis revealed that the inhibitory effect of intima
      proliferation is dose-dependent, and the 30 mg x mL(-1) nanoparticle
      concentration suspension could completely inhibit proliferation of intima.
      Paclitaxel-loaded nanoparticles through surface modification with DMAB provide an
      effective means of inhibiting proliferation response to vascular injury in the
      rabbit.

PMID- 17520814
TI  - [Characteristics of uptake, transport and efflux of Z- and E-ajoenes in Caco-2
      cell monolayers in vitro].
AB  - The characteristics of uptake, transepithelial transport and efflux of Z- and E
      ajoenes isolated from the bulbs of Allium sativum were studied. A human colon
      cell model Caco-2 cell monolayers in vitro cultured had been applied to study the
      characteristics of uptake, transepithelial transport and efflux of Z- and E
      ajoenes. The quantitative determination of Z- and E-ajoenes was performed by high
      performance liquid chromatography. Z- and E-Ajoenes can be detected only in the
      apical side and can be metabolized, but both compounds can not be transported
      from apical-to-basolateral and basolateral-to-apical directions in cultured Caco
      2 cell monolayers. The metabolism of Z- and E-ajoenes in Caco-2 cell monolayers
      can be partially inhibited by vitamin C as an anti-oxidant, metyrapone as an
      inhibitor to subtype CYP3A of cytochrome P450 drug metabolism enzymes, and sodium
      azide as an inhibitor to ATP production. It is shown that neither Z-ajoene nor E
      ajoene can pass through Caco-2 cell monolayers, and that they can be metabolized
      by the cells. The metabolism might be in correlation with cytochrome P450 drugs
      metabolism enzymes in Caco-2 cell monolayers.

PMID- 17520815
TI  - [Correlation between ITS genotype and geographical distribution of Pogostemon
      cablin].
AB  - To investigate the correlation between genotype and distribution of Pogostemon
      cablin by sequencing ITS1 and ITS2 genes, and provide molecular information for
      its germplasm evaluation, ITS1 and ITS2 genes of Pogostemon cablin from different
      localities were identified by PCR direct sequencing. The sequences of ITS1 and
      ITS2 genes were 424 bp and 380 bp in length, respectively. And nineteen base
      substitutions were observed in ITS1 gene, and five in ITS2 gene. The results
      showed a good correlation between genotype and distribution of Pogostemon cablin,
      and ITS gene sequencing could provide useful molecular information for germplasm
      evaluation of the plant species verification.

PMID- 17520816
TI  - [Allele-specific diagnostic PCR authentication of Dendrobium thyrsiflorum].
AB  - The aim of this study was to establish a diagnostic PCR method for authentication
      of D. thyrsiflorum Rchb. f. Based on rDNA ITS sequences of the 164 samples from
      109 Dendrobium species sequenced and quoted from GenBank, the allele-specific
      diagnostic primers QH-JB1 and QH-JB2 for authentication were designed. Using the
      primers, diagnostic PCR was performed with the total DNA of D. thyrsiflorum Rchb.
      f. and other D. species as templates to establish the positive PCR condition for
      D. thyrsiflorum Rchb. f. A DNA fragment about 300 bp was amplified from D.
      thyrsiflorum Rchb. f. with anneal temperature at 63.5 degrees C and anneal time
      at 1 min, whereas no other DNA fragment was amplified from the rest D. species.
      The allele-specific diagnostic PCR was proved to be a simple and quick
      identification technique, suitable for the authentication of both fresh and dried
      materials of D. thyrsiflorum Rchb. f.

PMID- 17520818
TI  - [Synthesis and antimicrobial activity of N-[ 5-(3-pyridyl)-1, 3, 4-thiadiazol-2
      yl] -N'-aroyl urea].
AB  - To synthesize and evaluate antimicrobial activity of novel heterocyclic
      compounds, the corresponding title aroyl ureas have been synthesized by the
      reaction of 2-amino-5-(3-pyridyl)-1, 3, 4-thiadiazole with aroyl isocyanates.
      Their antimicrobial activities in vitro were tested by disk diffusion methods and
      broth microdilution according to M-27A protocol recommended by NCCLS. Twelve new
      compounds were obtained, and their structures were confirmed by MS, IR, 1H NMR
      and elemental analysis. The biological screening tests showed that most of the
      compounds have some antifungal activities in vitro. Aroyl ureas incorporating
      pyridyl thiadiazole ring may be developed as novel antifungal candidate drugs and
      are worthwhile to be further studied.

PMID- 17520817
TI  - [Effect of griffithin on anticancer activity and apoptosis of cancer cells in
      vitro].
AB  - To study the anticancer activity of griffithin from Streptocaulon griffithii
      Hook. f. and its effect on apoptosis of cancer cells in vitro, the inhibitory
      effect of griffithin on cell proliferation was studied by MTT assay, the cell
      apoptosis was observed by AO/EB double decoration assay and flow cytometry.
      Griffithin exhibited high anticancer activity on four human cancer cell lines,
      with IC50 ranged from 0.17 - 0.43 microg x mL(-1). Griffithin also induced
      apoptosis of PC-3 cells. Griffithin had anticancer activity and induced apoptosis
      of cancer cells.

PMID- 17520819
TI  - [Advances in the study of anti-atherosclerosis drugs].
AB  - Several new drug targets of anti-atherosclerosis, emerging in the recent years,
      such as PPAR agonists, cholesteryl ester transfer protein (CETP) inhibitors,
      infusion of apolipoprotein A-I (apoA-I), liver X receptor (LXR) activators and
      phospholipid transfer protein (PLTP) inhibitors etc were reviewed.

PMID- 17520820
TI  - [Natural products in clinical trials: antibacterial and antifungal agents].
AB  - Natural products have played an important role in drug discovery. Today,
      therapeutics from natural origin count for about 70% of the worldwide human
      therapeutic sales. For anti-infective treatment even higher figures are reported.
      This review describes antibacterial and antifungal natural products, semi
      synthetic natural products and natural product derived compounds undergoing
      clinical evaluation or registration from 1998 to end of 2005. In addition,
      natural product derived drugs launched since 1998 are also discussed in this
      review.

PMID- 17520821
TI  - [Oral vaccination and vaccine-entrapped microparticle delivery system].
AB  - In order to elucidate the physiological basis for mucosal immunity of oral
      vaccination and to present the essential carrier of microparticles or
      nanoparticles used to investigate the orally delivered vaccine, the features of
      antigen presentation and mucosal immunereaction in gut-associated lymphoid
      tissues were analyzed. Considered the morphological and physiological barriers of
      the gastrointestinal tract, absorption and transport of particulates were further
      discussed. And the studies about particulate dosage forms for oral vaccine
      delivery were also summarized in this review. Peyer s patches and M-cells,
      involved in immunoregulation, are significant areas performing the critical role
      in oral vaccine. The applied vesicle of microparticles could overcome the
      barriers of gastrointestinal tract. Oral vaccination was endued with new
      connotation, especially the enhanced transport and immunization efficiencies
      promoted by the lectin anchored particles. In conclusion, oral vaccination
      mediated by particulate carrier via mucosal immune system, would contribute to
      the site-specific triggering and signal magnification. For vaccines, the
      prospects for the application of these promising carrier systems might have
      potential attraction for scientific research and commercial development.

PMID- 17520822
TI  - [Protective effect of rupatadine against oleic acid-induced acute lung injury in
      rabbits].
AB  - Acute lung injury (ALI) makes up a spectrum of disease that is commonly defined
      as "acute non-cardiogenic edematous lung injury". It may contribute to morbidity
      and mortality in the critically ill patient in the intensive care unit. ALI was
      induced by oleic acid in rabbits. During the experiment, blood samples were taken
      from cervical artery and subjected to blood-gas analysis at different time points
      after oleic acid injection. Shortly after the rabbits were killed at 3 hour after
      iv OA injection, bronchoalveolar lavage fluid (BALF) was colleted, and the
      concentrations of protein, platelet-activating factor (PAF), intercellular
      adhesion molecule-1 (ICAM-1), interleukin 8 (IL-8) in BALF were then measured by
      ELISA. The ratio of wet to dry weight (W/D) of left lung was calculated to assess
      alveolar edema. Lung tissue was fixed in formaldehyde and stained with HE, and
      examined under a light microscope. The OA-induced elevation of arterial blood
      oxygen pressure was inhibited, as well as PAF, ICAM-1, IL-8 in BALF in rupatadine
      group. Furthermore, rupatadine also decreased the concentration of protein in
      BALF and inhibited the increase of the W/D weight ratio significantly. Light
      microscopic findings showed that the damage in rupatadine groups was far less
      severe than that in OA model group. Pretreatment with rupatadine has a beneficial
      effect on acute lung injury induced by oleic acid in rabbits. The ultimate
      reduction of inflammatory factors was involved, at least in part, in the
      mechanism of action of rupatadine effects.

PMID- 17520823
TI  - [Effect of nordy on FPR function of malignant human glioma cell line U87].
AB  - Nordy is a synthesized chrial compound. To investigate the effects of nordy (25 -
      100 micromol x L(-1)) on the function of formylpeptide receptor (FPR) of
      malignant human glioma cells, human glioblastoma cell line U87 was used to detect
      its proliferation, migration, calcium mobilization, vascular endothelial growth
      factor (VEGF) mRNA and protein levels after activation of FPR by its agonist N
      formyl-methionyl-leucyl-phenylalanine (fMLF). Cell proliferation, migration
      ability, VEGF mRNA, VEGF protein and calcium mobilization were evaluated by cell
      counting, chemotaxis assay, RT-PCR, ELISA and spectrometry. Nordy (50 - 100
      micromol x L(-1)) potently inhibited the proliferation, migration and calcium
      mobilization of U87 cells induced by fMLF (P < 0.05). Moreover, 100 micromol x L(
      1) nordy showed a significantly impaired VEGF mRNA expression and protein
      secretion induced by fMLF (P < 0.05). Nordy could inhibit FPR functioning in
      glioma cell proliferation, migration and angiogenesis, which might be a possible
      mechanism of its anti-cancer effects.

PMID- 17520824
TI  - [Protective effect of silibinin against isoproterenol-induced injury to cardiac
      myocytes and its mechanism].
AB  - Silibinin is a polyphenolic flavanoid derived from fruits and seeds of milk
      thistle (Silybum marianum). To investigate the effect and mechanism of silibinin
      on beta-isoproterenol-induced rat neonatal cardiac myocytes injury, the
      viability, the activation of lactate dehydrogenase (LDH) and the content of
      maleic dialdehyde (MDA) were chosen for measuring the degree of cardiac myocytes
      injury. Superoxide dismutase (SOD) activity, mitochondrial membrane potential
      (deltapsi) detected by flow cytometric analysis, and Western blotting analysis
      were applied to determine the related proteins. Silibinin protected isoproterenol
      treated rat cardiac myocytes from death and significantly decreased LDH release
      and MDA production. Silibinin increased superoxide dismutase (SOD) activity, and
      increased mitochondrial membrane potential (deltapsi). Furthermore, the release
      of pro-apoptotic cytochrome c from mitochondria was reduced by silibinin.
      Silibinin increased the expression of anti-apoptotic Bcl-2 family protein Bcl-2,
      and up-regulation of SIRT1 inhibited the translocation of Bax from cytoplasm to
      mitochondria, which caused mitochondrial dysfunction and cell injury. Silibinin
      protects cardiac myocytes against isoproterenol-induced injury through resuming
      mitochondrial function and regulating the expression of SIRT1 and Bcl-2 family
      members.

PMID- 17520825
TI  - [Detection of binding activity and biologic effect of a novel alpha-melanocyte
      stimulating hormone analogue].
AB  - Binding activity and biologic effect of a novel alpha-melanocyte-stimulating
      hormone analogue were tested on cells transiently expressing the human
      melanocortin-1 (MC1), MC3, MC4, and MC5 receptors. The human MC1 and MC5 receptor
      genes were cloned into the expression vector pcDNA3. 1/ myc-his(-) B. The vectors
      were transferred to HEK-293 cells by the calcium phosphate method. Stable
      receptor populations were generated using G418 selection (900 microg x mL(-1))
      for subsequent bioassay analysis. K(i) values of the novel alpha-MSH analogue for
      MC1, MC3, MC4, and MC5 receptors were obtained in competition with [125I]-NDP-MSH
      for binding studies. The cyclic AMP level was tested by using [3H]-cyclic AMP
      kit. It is showed that K(i) values of the novel alpha-MSH analogue for MC1, MC3,
      MC4, and MC5 receptors were (0.159 +/- 0.040), (35.430 +/- 6.743), (19.293 +/-
      2.780) and (2.230 +/- 0.670) nmol L(-1), respectively. Its EC50 values for MC1,
      MC3, MC4, and MC5 receptors were (0.45 +/- 0.07), (7.80 +/- 0.65), (2.55 +/-
      0.23) and (0.33 +/- 0.09) nmol L(-1), respectively. In these tests, the novel
      alpha-MSH analogue is a MC1R and MC5R selective agonist.

PMID- 17520826
TI  - [Preparation and antitussive, expectorant and antiasthmatic activities of
      verticinone-bile acids salts].
AB  - To search for potential drugs with potent antitussive, expectorant, antiasthmatic
      activities and low toxicity, a series of verticinone-bile acids salts were
      prepared based on the clearly elucidated antitussive, expectorant and
      antiasthmatic activities of verticinone in bulbs of Fritillaria and different
      bile acids in Snake Bile. The antitussive, expectorant and antiasthmatic
      activities of these verticinone-bile acid salts were then screened with different
      animal models. Ver-CA (verticinone-cholic acid salt) and Ver-CDCA (verticinone
      chenodeoxycholic acid salt) showed much more potent activities than other
      compounds. The bioactivities of Ver-CA and Ver-CDCA are worthy to be intensively
      studied, and it is also deserved to pay much attention to their much more potent
      antitussive effects than codeine phosphate. In order to elucidate whether they
      have synergistic effect and attenuated toxicity, their activities will be
      continuously compared with single verticinone, cholic acid and chenodeoxycholic
      acid at the same doses on different animal models. The application of
      "combination principles" in traditional Chinese medicinal formulations may be a
      novel way in triditional Chinese medicine research and discovery.

PMID- 17520827
TI  - [Construction of pharmacophore model of PARP-1 inhibitor].
AB  - To construct the pharmacophore model of the poly (ADP-ribose) polymerase-1
      inhibitor and to investigate the possible inhibitory mechanisms, ten
      pharmacophore models of PARP-1 inhibitor were established from the training set
      of thirty-eight PARP-1 inhibitors with conformer analysis and pharmacophore
      mapping by using the Catalyst software. Based on the mechanism of action and the
      known structure-activity relationship of PARP-1 inhibitor, an optimal
      pharmacophore model including two hydrogen-bonding acceptors and two aromatic
      hydrophobic core was confirmed. The reliability of the optimal pharmacophore
      model is preferably with RMS = 0.46, Correl = 0.91, Weight = 2.06, and Config =
      15.97. This pharmacophore model not only provided some information about the
      interaction between enzyme and compound, but also showed excellent forecast
      ability and contributes to design the PARP-1 inhibitors with undiscovered
      structure.

PMID- 17520828
TI  - [Chemical constituents from flos Sesamum indicum L].
AB  - Sesame (Sesamum indicum L. ) belongs to Pedaliaceae, and its dry flowers have
      been used to cure alopecia, frostbite and constipation as a Traditional Chinese
      Medicine. Interestingly, the Flos Sesamum indicum L. was usually used to cure
      verruca vulgaris and verruca plana in folk of China, and showed a pleasant
      result. Previous chemical investigations of this plant mainly concentrate on its
      seeds, showed the presence of proteins and fat oils, herein we make a systematic
      chemical research on the dry flowers of this plant. Column chromatography
      including silica gel, C18 and Sephadex LH-20 were used to separate the chemical
      constituents and the structures were determined by chemical and spectroscopic
      methods. Ten compounds were isolated from the 95% ethanol extract of the plant
      and elucidated as latifonin (1), momor-cerebroside (2), soya-cerebroside II (3),
      1-O-beta-D-glucopyranosyl-(2S, 3S, 4R, 5E,9Z)-2-N-(2'-hydroxytetracosanoyl) 1,3,4
      trihydroxy-5,9-octadienine (4), 1-O-beta-D-glucopyranosyl-(2S, 3S, 4R, 8Z)-2-N
      (2' R) 2'-hydroxytetracosanoyl) 3,4-dihydroxy-8-octadene (5), (2S, 1" S) 
      aurantiamide acetate (6), benzyl alcohol-O-(2'-O-beta-D-xylopyranosyl, 3'-O-beta
      D-glucopyranoside)-beta-D-glucopyranoside (7), beta-sitosterol (8), daucosterol
      (9) and D-galacititol (10). Among them, 4 is a new compound, and others were
      isolated from the flowers of the plant for the first time. Compounds 2 to 4
      belong to cerebroside, which is rare to be found in land plants and was proved to
      possess many bioactivities.

PMID- 17520829
TI  - Chemical constituents from the roots of Homonoia riparia.
AB  - A new compound and twelve known compounds were isolated from the ethyl acetate
      extract of the roots of Homonoia riparia Lour, which are used in folk medicine
      for treatment of hepatitis, bellyache and scald, by the method of silica gel
      column chromatography repeatedly with a gradient of PE-EtOAc, PE-Me2CO, CHCl3
      Me2CO, CHCl3-MeOH. Their structures were identified as a new compound 1-oxo
      aleuritolic acid (1), and twelve known compounds aleuritolic acid (2), 3-acetoxy
      aleuritolic acid (3), taraxerone (4), taraxerol (5), methyl 3-acetoxy-12-oleanen
      28-oate (6), 3-acetoxy-12-oleanen-28-ol (7), ursolic acid (8), lupenol (9), 3beta
      acetoxy-lupenol (10), cleomiscosin A (11), chrysophanol (12), and gallic acid
      (13), which were obtained from this plant for the first time, by the
      spectroscopic techniques of NMR, HMBC, IR and MS, separately. Among the
      cytotoxicities evaluation of compounds 1 -3 towards AGZY 83-a (human lung cancer
      cells) and SMMC-7721 (human liver cancer cells) tumor cells was assayed by MTT
      methods with cis-dichlorodiamminoplatinum (DDP) used as positive control.
      Compound 2 exerted weak activity against AGZY 83-a with the IC50 value of 33.055
      microg x mL(-1), while 1 and 3 showed no activity to these two cell lines.

PMID- 17520830
TI  - [Pharmacokinetics of pingyangmycin hydrochloride in rabbits determined by
      microdialysis coupled with RP-HPLC].
AB  - Microdialysis coupled with RP-HPLC was used to study the blood pharmacokinetics
      of pingyangmycin hydrochloride in rabbits. Supelco RP-amide C16 column was
      adopted for the analysis of pingyangmycin hydrochloride. The data was analyzed
      with 3P87 program. The calibration curve was linear in the concentration range
      from 1.04 to 66.56 microg x mL(-1) (r2 = 0.999 4). The in vivo recovery of
      microdialysis probe was (42.8 +/- 3.4)% (n = 4). The concentration-time curve of
      pingyangmycin hydrochloride was fitted to two-compartment model. T1/2 alpha and
      T1/2 beta were 14.9 and 60.3 min, respectively. The method is proved to be
      accurate, simple and suitable for the pharmacokinetics study of pingyangmycin
      hydrochloride in rabbits.

PMID- 17520831
TI  - [Pharmacokinetic interactions between the main components in the extracts of
      Salvia miltiorrhiza Bge. in rat].
AB  - The pharmacokinetics of the main components of protocatechualdehyde, salvianolic
      acid B, tanshinone II(A), cryptotanshinone, and the hydrophilic or lipophilic
      extracts of Salvia Miltiorrhiza Bge., in rat plasma were studied after oral
      administration separately to explore the interactions between them. Some
      components in the hydrophilic extract depress the absorption of the
      protocatechualdehyde, on the contrary, enhance the absorption of the salvianolic
      acid B and depress its elimination rate. The concomitant components in the
      lipophilic extract might enhance the absorption of cryptotanshinone and its
      distribution from the centre compartment to the peripheral compartment, and the
      metabolism to tanshinone II(A). The 'concomitant components' in the extract of
      Chinese material medica had significant effect on the pharmacokinetics of its
      'marker components'. It can not only be rival, synergic, but also have the
      effects on metabolism. Therefore the traditional Chinese medicine was a
      complicated system, It should be taken a scientific and dialectic view in the
      research and development processes.

PMID- 17520832
TI  - [Determination of ambroxol and clenbuterol in human plasma by LC-MS/MS method].
AB  - Ambroxol and clenbuterol were extracted from human plasma samples by liquid
      liquid extraction, ambroxol was separated on a Zorbax XDB-C18 column and detected
      by tandem mass spectrometry with an atmospheric pressure chemical ionization
      interface after oral administration of a compound preparation. Clenbuterol was
      separated on a Zorbax XDB-C8 column and detected by tandem mass spectrometry with
      an electrospray ionization interface. Diphenhydramine is used as the internal
      standard. The linear concentration ranges of the calibration curves for ambroxol
      and clenbuterol were 0.080 - 400 microg x L(-1) and 5.0 - 5 000 ng x L(-1),
      respectively. The lower limits of quantification were 0.080 microg x L(-1) for
      ambroxol and 5.0 ng x L(-1) for clenbuterol, individually. The inter-day and
      intra-day precision (RSD) across three validation run over the entire
      concentration range was below 7.5%, and the accuracy (RE) was within +/- 2.5% for
      both ambroxol and clenbuterol. The methods were used to determine the
      pharmacokinetic parameters of ambroxol and clenbuterol in human plasma after oral
      administration of a compound preparation containing 60 mg ambroxol hydrochloride
      and 40 microg clenbuterol hydrochloride. The method was proved to be highly
      sensitive, selective and suitable for the pharmacokinetic study of different
      compound preparations containing ambroxol and clenbuterol.

PMID- 17520833
TI  - [Factors influencing the content of residual tert-butyl alcohol in cyclodextrin
      complex prepared by lyophilization cosolvent system].
AB  - In order to minimize the residual tert-butyl alcohol (TBA) level in cyclodextrin
      complex prepared by freeze drying TBA/water cosolvent system, the formulation and
      lyophilization procedure that may influence the residual TBA was studied.
      Residual TBA in freeze dried cyclodextrin complex was determined by gas
      chromatography. The significant formulation and processing factors that influence
      residual TBA were identified by adjusting the initial TBA concentration in
      cosolvent, selecting cyclodextrin type (beta-cyclodextrin or hydroxypropyl beta
      cyclodextrin), changing sample volume in flasket, altering freezing mode (fast
      freezing or slow freezing) and modifying the duration of secondary drying. The
      results show that the amorphous cyclodextrin material (hydroxypropyl beta
      cyclodextrin), initial low TBA concentration in cosolvent and fast freezing would
      lead to high TBA residue in cyclodextrin complex, annealing was effective in
      reducing the residual TBA. The duration of secondary drying had no distinct
      effect on residual TBA. It is concluded that in order to reduce residual TBA in
      cyclodextrin complex prepared by lyophilization monophase solution, the initial
      TBA concentration in cosolvent should be higher than the crystal formation
      concentration, the appropriate cyclodextrin type and freeze drying processing
      should be choosen.

PMID- 17520834
TI  - [Preparation of Cu(2+)-loaded montmorillonite and its bactericidal mechanism
      against Escherichia coli].
AB  - The aims of this study were to prepare Cu(2+)-loaded montmorillonite (Cu-MMT) and
      investigate its bactericidal activity and mechanism. Cu-MMT was prepared by the
      method of ion exchange reaction. The structure and surface characteristic of Cu
      MMT were determined. Minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) of Cu-MMT against the strain of Escherichia coli
      were determined. The activities of intracellular enzyme in bacterial solution
      were measured, and the morphology of E. coli was observed during the interaction
      between Cu-MMT and bacteria. The results showed that treatment with Cu2+
      increased cation exchange capacity of montmorillonite, but specific surface area
      and surface negative charge density were decreased. The MIC and MBC of Cu-MMT
      against the tested E. coli were 0.16 and 0.64 mg x m(L(-1), respectively. Cu-MMT
      could destroy bacterial cellular membrane and then resulted in leakage of
      intracellular enzymes such as asparate aminotransferase, lactate dehydrogenase
      and alanine aminotransferase. These suggest that Cu-MMT has a strong bactericidal
      activity. The bactericidal mechanism of Cu-MMT may be that bacteria are adsorbed
      by Cu-MMT, and then morphology and permeability of cellular membrane are changed.
      This leads to an efflux of intracellular contents and the death of bacteria.

PMID- 17520835
TI  - [Free amino groups on the surface of chitosan nanoparticles and its
      characteristics].
AB  - The relationship of free amino groups on the surface and the characteristics of
      chitosan nanoparticles (CS-NPs) prepared by ionic gelation method was
      investigated. Free amino groups on the surface of CS-NPs were determined by
      colloidal titration, and the effects of the amount of free amino groups and its
      ionizable level on the particle size, zeta potential, appearance, drug entrapment
      efficiency and drug release profile in vitro of CS-NPs were investigated. The
      result showed that the surface free amino groups reduced, the average size, zeta
      potential, stability of nanoparticles, and the drug release rate and degree all
      decreased while the drug entrapment efficiency was not affected with the increase
      of tripolyphosphate (TPP) concentration. With the increase of pH, the free amino
      groups could be deprotonated and the ionizable level was stepped down,
      correspondingly the particle size and zeta potential of CS-NPs decreased.
      Additionally, the drug release rate and degree were elevated in acid medium while
      descended in neutral or base medium. The amount and ionizable level of free amino
      groups on the surface are affected by the gelation degree and pH, which further
      affected the volume phase transitions (swelling/shrinking processes) of CS-NPs.
      The properties of CS-NPs have correlation with the surface free amino groups.

PMID- 17520836
TI  - [A new molecular identification method: anchored primer amplification
      polymorphism DNA].
AB  - To build up a stable and easy doing method for molecular identification in
      traditional Chinese medicine, on basis of RAPD, the new method mainly changed the
      primer length and PCR annealing temperature. Panax ginseng, Panax quinquefolius
      and its nine adulterants were used to establish the method and test it using
      MARMS primers published in 2004. The new method also used to authenticate Chinese
      Materia Medica of Tian-hua-fen (Radix Trichosanthes) and Bai-zhi (Radix
      Angelica). Primer Pg-q36F obtained polymorphic bands of P. Ginseng, P.
      quinquefolius and its adulterants. The identification result is identical to that
      published before and more stable. Primer TkS1-64F obtained polymorphic bands of
      Tian-hua-fen and its nine adulterants. Primer AfS1-100F obtained polymorphic
      bands of Bai-zhi and its three adulterants. The method has good stability and
      reproducibility and can easily identify authertic medicines from their
      adulterants. It was a potential molecular method to identify other Chinese
      Materia Medica. The method was named as anchored primer amplification
      polymorphism DNA (APAPD).

PMID- 17520837
TI  - [Effect of berberine on left ventricular remodeling in renovascular hypertensive
      rats].
AB  - The purpose of this study is to evaluate the effects and the underline mechanisms
      of berberine on the cardiac function and left ventricular remodeling in rats with
      renovascular hypertension. The renovascular hypertensive model was established by
      the two-kidney, two-clip (2K2C) method in Sprague-Dawley (SD) rats. Two weeks
      after surgery, all the operated SD rats were randomly assigned into four groups:
      (1) renovascular hypertensive model group; (2) berberine 5 mg x kg(-1) group; (3)
      berberine 10 mg x kg(-1) group; (4) captopril 45 mg x kg(-1) group; and the sham
      operated rats were used as control. Four weeks after the drugs were administered,
      the cardiac function was assessed. The ratios of heart weight to body weight
      (HW/BW), left ventricular weight to body weight (LVW/BW) and right ventricular
      weight to body weight (RVW/BW) were compared between groups. Coronal sections of
      the left ventricular tissue (LV) were prepared for paraffin sections, picrosirius
      red and HE staining was performed. The left ventricular wall thickness (LVWT),
      interventricular septal thickness (IVST), the parameters of myocardial fibrosis
      indicated by interstitial collagen volume fraction (ICVF) and perivascular
      collagen area (PVCA) were assessed. Nitric oxide (NO), adenosine cyclophosphate
      (cAMP) and guanosine cyclophosphate (cGMP) concentrations of left ventricular
      tissue were measured. Berberine 5 mg x kg(-1) and 10 mg x kg(-1) increased the
      left ventricular +/- dp/dt(max) and HR. Berberine 10 mg x kg(-1) decreased HW/BW
      and LVW/BW. The image analysis showed that both 5 and 10 mg x kg(-1) of berberine
      decreased LVWT, ICVF and PVCA, while increased the NO and cAMP contents in left
      ventricular tissue. Berberine could improve cardiac contractility of 2K2C model
      rats, and inhibit left ventricular remodeling especially myocardial fibrosis in
      renovascular hypertension rats. And such effects may partially associate with the
      increased NO and cAMP content in left ventricular tissue.

PMID- 17520838
TI  - Interaction between traditional Chinese medicine and Western medicine in rats--In
      Chen-How and acetaminophen.
AB  - The purpose of this study is to evaluate the interaction effects of In-Chen-How
      (Artemisia capillaries Thunb.) on the pharmacokinetics of acetaminophen and on
      liver microsomal cytochrome P450 enzyme activity in rats. The rats were divided
      into control group (n = 8) without In-Chen-How and the pretreated group (n = 8)
      administered with In-Chen-How (approximately 1.0 mL x kg(-1), according to
      weight) for 5 consecutive days. Rats in the control group received water
      simultaneously. Each rat was then given acetaminophen. The pharmacokinetic
      parameters of acetaminophen of the two groups were significantly different. In
      the In-Chen-How pretreated group, the maximum concentration of acetaminophen and
      the area under the plasma concentration-time curve were reduced about 58.4%,
      56.7% and 55.4%. To further explain the results, liver microsomal suspensions
      were obtained from rats that were randomly divided into control and In-Chen-How
      pretreated group. The levels of CYP1A2 and CYP2E1 in hepatic microsomal protein
      from pretreated group were increased as compared to that from the control group.
      It indicated that In-Chen-How can stimulate the activity of CYP isozymes. The
      changes in the pharmacokinetics of acetaminophen resulting from the
      administration of In-Chen-How are related to an increase in metabolic activity of
      CYP1A2 and CYP2E1.

PMID- 17520839
TI  - [Situs inversus, situs inversus totalis (in adults)].

PMID- 17520840
TI  - [Sexual medicine in primary care--development in the years 1980-1990-2004].
AB  - Sexual disorders are common in community samples. Even so these problems are not
      often addressed by primary care physicians. In 1980, 1990, and 2004 three cohorts
      of primary care physicians in the German speaking part of Switzerland were asked
      to answer a questionnaire on the prevalence of sexual problems and disorders in
      their patients and their knowledge in sexual medicine. The prevalence of sexual
      disorders in primary care is underestimated by primary care physicians. Female
      doctors and female patients address sexual problems more often than male doctors
      and patients. Lack of sexual interest and erectile dysfunction are the most
      frequent sexual disorders in primary care. In 2004 the participating doctors
      assess their knowledge in sexual medicine at a higher level compared to 1980. The
      training of primary care physicians in primary care should further be improved.

PMID- 17520841
TI  - [Chronic lymphocytic leukemia and loss of strength in the right arm--not a
      typical combination].
AB  - We report a case of metastatic renal cancer as a second malignancy in a patient
      with chronic lymphocytic leukemia (CLL). Six years after the primary CLL
      diagnosis, the clinical presentation of this patient was not typical for CLL,
      requiring further diagnostic steps. Due to the long-lasting course of CLL second
      cancers can occur in these patients. In addition some forms of tumors, such as
      Kaposi sarkoma, malignant melanoma, laryngeal carcinoma, lung cancer and Hodgkin
      Lymphoma are found more frequently in this patient population. Men with CLL have
      an increased risk for brain tumors, women for gastric and bladder cancers.

PMID- 17520842
TI  - [Bleeding complication due to accumulation of low-molecular-weight heparin in a
      patient with renal insufficiency].
AB  - We report of a 71-year-old woman with a history of chronic analgesic nephropathy,
      who underwent coronary angiography. Because of anterior ventricular aneurysm,
      anticoagulation with nadroparine was installed. Continued ACE-inhibitor and ASA
      with additional intravenous contrast substance lead to acute tubular necrosis
      with rapid decline of the renal function. Due to accumulation of the low
      molecular weight heparin, the patient developed an extensive retroperitoneal
      haematoma with circulatory shock and temporary anuric kidney failure. Low
      molecular weight heparins are commonly used during percutaneous coronary
      interventions. They are as safe and efficient compared to unfractioned heparin.
      But due to their renal elimination, they have to be monitored by measuring anti
      factor Xa-activity if creatinine-clearance is <30 ml/min.

PMID- 17520843
TI  - [A rare case of secondary hypertension].

PMID- 17520844
TI  - ["This science is the most noble of all sciences" -- on relations of religion and
      medicine in Bahaism].

PMID- 17520845
TI  - [Skin eruptions as an adverse reaction to epidermal growth-factor receptor
      inhibitors].
AB  - Inhibition of the epidermal growth-factor receptor (EGFR) is a new strategy in
      the treatment of solid malignancies. Two men, aged 65 and 59 years, with a
      metastasized renal carcinoma and a 51-year-old man with a metastasized melanoma
      developed an acneiform eruption during EGFR inhibition. The second and third
      patient also developed paronychia. Treatment in all patients consisted of
      antiseptics and topical antibiotics; the first and third patient also received an
      oral antibiotic. Withdrawal of the EGFR inhibitor because of progression of the
      disease led to complete recovery of the cutaneous lesions in the first and the
      third patient; both died after several months. In the second patient, the side
      effects reached an acceptable level during continued EGFR therapy. EGFR
      inhibition is usually accompanied by cutaneous side effects. An acneiform
      eruption is seen in up to 90% of all treated patients. Other side effects include
      dry skin, and nail and hair changes. The pathogenesis of these side effects is
      related to inhibition of EGFR signalling pathways in the skin, but is not yet
      fully understood. The treatment of EGFR inhibitor-mediated cutaneous toxicity is
      based mainly on clinical experience.

PMID- 17520846
TI  - [Electromagnetic fields: damage to health due to the nocebo effect].
AB  - Environmental exposure to man-made electromagnetic fields has been steadily
      increasing as the growing demand for electricity and advancing technology have
      created many artificial sources. Over the course of the past decade, numerous
      sources of electromagnetic fields have become the focus of health scares, most
      recently mobile phones and their base stations. The predictable reaction to these
      health scares has been 'more research'. This comment argues that studies of the
      possible hazards of low-level electromagnetic fields waste scarce financial
      resources. Many studies have convincingly excluded detectable tangible health
      hazards. Bayesian logic predicts that the likelihood of false-positive results
      will be great in studies lacking a prior hypothesis and using non-specific health
      states as outcomes. The health hazards due to the maintenance of environmental
      scares by false-positive studies have been neglected. The nocebo hypothesis
      states that expectations of sickness cause sickness in the expectant individual.
      Maintaining anxiety by fostering doubts in gullible populations about the quality
      ofthe environment they live in may cause serious mental illness. Anxiety caused
      by health scares is an increasing public health problem, which should be
      addressed in its own right.

PMID- 17520847
TI  - [Performance indicators unsuitable to monitor and improve complex health care].
AB  - Medically, socially and legally doctors are expected to deliver care of
      sufficient quality. Adequate quality is never self-evident. Patients and payers
      increasingly demand public disclosure of the condition ofhealthcare. Performance
      indicators have been created for this purpose, but how adequate are these
      measures? The problem is complex, making single performance indicators, such as
      the percentage of patients with traumatic hip fracture who undergo surgery within
      24 hours after admission, inadequate. Improving quality requires not only proper
      measurement to disclose weaknesses and monitor the road to recovery but also
      better motivation of healthcare professionals. Pay-for-performance does not
      address the basic problems ofhow to measure and improve care. Doctors have to
      change the culture of medicine and find ways to deal with the increasing
      complexity of medical care.

PMID- 17520848
TI  - [Endovenous laser therapy: a new treatment for varicose veins].
AB  - Varicose veins are very common. For years the most commonly applied treatment for
      great saphenous vein (GSV) insufficiency was saphenofemoral junction ligation
      with saphenous vein stripping. Minimally invasive methods, such as the endovenous
      laser therapy, are increasingly used during the last few years. In endovenous
      laser therapy, a diode laser fibre is inserted percutaneously into the GSV using
      ultrasonography to confirm the position. Thermal laser energy is applied to the
      endothelium ofthe GSV, resulting in local venous occlusion. The procedure has
      rapidly become popular with clinicians who treat varicose veins due to its
      relative simplicity and high rate of patient satisfaction. Efficacy outcomes are
      good with an occlusion rate of up to 100%. Recanalisation is rarely occurring
      even after several years. Pain, haematoma and phlebitis are common adverse events
      associated with endovenous laser therapy but in most cases are self-limiting.
      Serious adverse events, such as deep vein thrombosis, are uncommon. The
      advantages ofendovenous laser therapy are the lack of surgical wounds, so
      infection and scarring are avoided, and that the procedure can be performed in an
      outpatient setting using local anaesthesia. Endovenous laser therapy appears to
      be a safe and effective treatment option for refluxing varicose veins.

PMID- 17520849
TI  - [Diagnostic image (321). A girl with 'bruises' on her abdomen].
AB  - A 12-year-old girl presented with a reticular skin abnormality on her abdomen,
      which was caused by the frequent use of hot water bottles to relieve her chronic
      stomachache. This skin condition is called erythema ab igne.

PMID- 17520850
TI  - [Retrospective application of the performance indicator 'hip fracture: operate
      within 24 hours' in 217 patients treated at the University Medical Centre Utrecht
      in 2000-2003: reduction in postoperative pneumonia but not mortality].
AB  - OBJECTIVE: To evaluate whether patients with hip fracture who undergo surgery
      within 24 hours--which has been propagated as an indicator of quality care--is
      associated with a reduced risk of mortality and complications, compared with
      later surgery. DESIGN: Retrospective status study based on a prospectively
      designed electronic medical record. METHOD: Data were collected on patients aged
      > or =60 years who were admitted to the University Medical Centre Utrecht, the
      Netherlands, between 1 January 2000 and 31 December 2003 for hip fracture.
      Outcomes were compared in patients who underwent surgery within 24 hours and
      those who underwent surgery after more than 24 hours. The primary outcome measure
      was mortality (in-hospital, after 3 months, 12 year and 3 years after discharge).
      Secondary outcome measures were postoperative complications, postoperative
      duration ofhospital stay and admission to long-term care facilities. We corrected
      for age, gender and pre-existing comorbidity. RESULTS: A total of 217 patients
      were included. In the 150 patients who underwent surgery within 24 hours, the
      mean age was 80.5 years, 75% were female and 28% were class III or IV according
      to the American Society of Anesthesiologists (ASA). In the 67 patients who
      underwent surgery after more than 24 hours, the mean age was 80.9 years, 82% were
      female, and 49% were ASA class III or IV. After correcting for published risk
      factors, there was no relationship between the timing of surgery and mortality.
      Fewer patients treated within 24 hours developed pneumonia postoperatively. In
      this study population, the only risk factor for mortality was the preoperative
      condition of the patient. CONCLUSION: Postoperative pneumonia occurred less
      frequently in patients with hip fracture who underwent surgery within 24 hours.
      Postoperative mortality was related to poor patient condition but not the timing
      of surgery. Early surgery should be avoided in patients with severe comorbidity
      who are not optimally prepared for surgery.

PMID- 17520851
TI  - [Two patients with an isolated traumatic rupture of the subscapular tendon].
AB  - A man aged 65 and a woman aged 55 were referred to the orthopaedic clinic because
      of persistent pain in the right shoulder following a fall, 5 and 16 months
      earlier respectively. On physical examination they were found to have a painful
      shoulder and loss of strength on endorotation of the right arm. Ultrasound
      examination of the shoulder revealed subscapular tendon rupture in both patients,
      this was confirmed by MRI scan in the first patient. Treatment was operative
      repair of the tendon by a deltopectoral approach, followed by wearing a
      exorotation-limiting sling. After six months the first patient was free of
      complaints and the second patient was still experiencing pain when laying on the
      right shoulder. An isolated traumatic rupture of the subscapular tendon is
      uncommon and is often misdiagnosed or only discovered later. This diagnostic
      delay negatively influences the success of operative treatment. Focusing
      attention on the typical trauma mechanism, the character of the symptoms and the
      use of simple physical examination such as the lift-offtest or the belly press
      test can lead to the correct diagnosis.

PMID- 17520852
TI  - [Metformin-related lactic acidosis in an 85-year-old woman].
AB  - An 85-year-old woman presented at the emergency ward. She had had shortness of
      breath for several days and no bowel movements for 3 days. On the day
      ofhospitalisation she experienced sudden abdominal pain and collapsed as she went
      to the toilet. She was being treated for multiple conditions, including type-2
      diabetes. She appeared to have lactic acidosis. At first, the symptoms were not
      attributed to metformin because she was receiving a low dose and serum-creatinine
      concentrations were within the normal range (98 micromol/l). Bowel ischaemia was
      suspected and surgery was performed but no defects were found. She was
      subsequently treated for metformin-related lactic acidosis but died shortly
      thereafter due in part to postoperative complications. Lactic acidosis is a rare
      side effect of metformin. In this patient, the retrospectively calculated
      glomerular filtration rate (GFR) was extremely low (23 ml/min). The serum
      creatinine concentration was normal because the patient's body weight was low (40
      kg). Impaired renal function is a risk factor for metformin-related lactic
      acidosis. Renal function can appear to be normal when measured by serum
      creatinine concentration in older patients with reduced muscle mass, but
      calculation of GFR often reveals impairment. Metformin is contraindicated in
      patients with poor renal function. The increasing use of metformin in older
      patients for the treatment of diabetes mellitus warrants renewed attention to
      this severe side effect.

PMID- 17520853
TI  - [Fatal autointoxication with metformin].
AB  - A 39-year-old woman with type-2 diabetes mellitus presented with metabolic
      acidosis due to an attempted suicide with metformin. Despite treatment with
      activated charcoal and laxation, she experienced cardiac arrest, which required
      resuscitation. After transfer to another hospital, she was treated with high
      volume continuous venovenous haemofiltration. However, she died due to multiple
      organ failure. Metformin is the most widely used oral antidiabetic agent in the
      world and the first-choice treatment for patients with type-2 diabetes mellitus.
      Metformin overdose can cause lactic acidosis, which usually manifests as
      abdominal pain, vomiting and diarrhoea. Although rare, metformin-associated
      lactic acidosis carries a high mortality risk. The treatment of choice is
      immediate haemodialysis and orally administered activated charcoal. If a patient
      treated with metformin presents with metabolic acidosis, lactic acidosis due to
      metformin overdose should be suspected and appropriate treatment should be
      initiated immediately.

PMID- 17520854
TI  - [[Severe phenytoin intoxication in patients with hypoalbuminaemia].

PMID- 17520855
TI  - [Gait disorders due to neurological conditions].

PMID- 17520856
TI  - [Hospital top 100: changing rankings, changing reputations].

PMID- 17520857
TI  - Hyperbaric oxygen therapy and cerebral palsy--where to now?

PMID- 17520858
TI  - The life-saving effect of hyperbaric oxygenation during early-phase severe blunt
      chest injuries.
AB  - The effect of hyperbaric oxygenation (HBO2) on survival during the early phase of
      severe blunt chest injury (BChI) has not been elucidated. Our aim was to
      investigate this effect on human victims of BChI. We monitored cardiac index
      (CI), stroke volume index (SVI), PaO2 and PaO2/FiO2 in 18 victims treated
      conventionally, and 8 victims treated under combined conventional and HBO2
      treatment. Out of the 18 victims, 4 survived (Group A) and 14 died (Group B).
      Another 8 victims, in Group C, received HBO, and all survived. Human victims
      showed marked reductions in all cardiorespiratory values during the first 24 h.
      Group B persistently tended towards a decrease in SVI, PaO2/FiO2 and PaO2,
      eventually reaching fatal levels. The survivors developed a cardiorespiratory
      function characterized by a tendency towards recovery of all monitored
      parameters, more notable in Group C, which showed an earlier and more significant
      normalization vs. Group A (P<0.01). Our clinical data suggest that the earliest
      possible HBO2 treatment after severe blunt trauma can significantly enhance
      victims' survival.

PMID- 17520859
TI  - Lung metastatic load limitation with hyperbaric oxygen.
AB  - Despite some theoretical concern about cancer-enhancing effects ofhyperbaric
      oxygen (HBO2) therapy, it is frequently administered to cancer patients. We
      evaluated the growth of murine breast cancer cells in the lung after hyperbaric
      oxygen treatment in an experimental metastasis assay. Young nu/nu mice were
      injected intravenously with 3 x 10(3) 4T1-GFP tumor cells per g body weight
      followed by lung isolation, perfusion, and intact organ epifluorescence
      microscopy 1 to 37 days after injection. A group of animals (n=32) was exposed
      once daily for 5 days a week to 45 min of 2.8 ATA hyperbaric oxygen (HBO2) in a
      research animal HBO2 chamber. Control animals (n=31) were not subjected to HBO2
      treatment, but received similar intravenous administration of 3 x 10(3) 4T 1-GFP
      tumor cells. Single tumor cells and colonies were counted in the subpleural
      vessels in areas of about 0.5 cm2 of lung surface. HBO2 treatment did not lead to
      an increase in the number of the large or small colonies in the lungs. Rather, a
      significant reduction in the number of the large colonies was observed at 1 and
      16 to 21-day periods of measurements after hyperbaric treatment. However, most
      importantly, there was a significant decrease in large colony size in the HBO2
      group during all periods of observation. The results indicate that HBO2 is not
      prometastatic for breast cancer cells; rather it restricts the growth of large
      tumor cell colonies.

PMID- 17520860
TI  - Effects of sodium bicarbonate on voluntary face immersion breath-hold times.
AB  - The purpose of this study was to examine the effects of orally ingested sodium
      bicarbonate (NaHCO3) on voluntary breath-hold time with facial immersion. Eight
      non-elite breath-hold divers aged 20-41 (26.75 +/- 7.83 years) were recruited to
      undertake two bouts of three monitored, facial-immersion breath-holds, one week
      apart. Subjects were randomly allocated to double-blind sessions of ingesting an
      experimental (0.3 g x kg(-1) NaHCO3) or placebo (8 g NaCl) solution. Heart rate,
      pre- and post-breath-hold end-tidal gases, peripheral oxygen saturation (SpO2) at
      right index finger and maximum breath-hold times (Max-BHT) were recorded. Max-BHT
      was established during the third breath-hold in both trials. Max-BHT of 168.2 (+/
      20.7) sec and 145.7 (+/- 21.4) see were recorded for the experimental and
      placebo conditions, respectively (P = 0.019). Average bradycardic response did
      not differ between the experimental and placebo trials (P = 0.166). Whilst there
      was a significant difference in post-breath-hold end-tidal oxygen (P(ET) O2), one
      was not noted in end-tidal carbon dioxide (P(ET) CO2) measures (P = 0.048, and; P
      = 0.530, respectively). There was significant difference in lowest recorded SpO2
      (P = 0.008) between the trials. It is suggested that ingestion of NaHCO3, prior
      to facially immersed breath-holds, has an ergogenic effect, prolonging Max-BHT by
      approximately 8.6%.

PMID- 17520861
TI  - The relationship between venous gas bubbles and adverse effects of decompression
      after air dives.
AB  - The presence of gas bubbles in the vascular system is often considered a sign of
      decompression stress and several studies in the existing literature have
      addressed the relationship between the amount of bubbles detected by ultrasound
      Doppler systems and the incidence of decompression sickness. The use of
      ultrasound imaging has some important advantages to Doppler systems, and here we
      have looked at the relationship between the amount of intravascular gas bubbles
      detected by ultrasound echocardiography and the incidence of signs and symptoms
      of decompression stress after 203 air dives. The results show that venous gas
      bubbles detected by ultrasound imaging is a highly sensitive, although not
      specific, predictor of such adverse effects of decompression. Our results agree
      with the published concordance between Doppler detected bubbles and decompression
      sickness. We conclude that bubble detection by ultrasonic scanning of the heart
      can be used as a tool to assess the safety of decompression procedures for air
      dives.

PMID- 17520862
TI  - Effect of heliox, oxygen and air breathing on helium bubbles after heliox diving.
AB  - In helium saturated rat abdominal adipose tissue, helium bubbles were studied at
      101.3 kPa during breathing of either heliox(80:20), 100% oxygen or air after
      decompression from an exposure to heliox at 405 kPa for one hour. While breathing
      heliox bubbles initially grew for 15-115 minutes then shrank slowly; three out of
      10 bubbles disappeared in the observation period. During oxygen breathing all
      bubbles initially grew for 10-80 minutes then shrank until they disappeared from
      view; in the growing phase, oxygen caused faster growth than heliox breathing,
      but bubbles disappeared sooner with oxygen breathing than with heliox or air
      breathing. In the shrinking phase, shrinkage is faster with heliox and oxygen
      breathing than with air breathing. Air breathing caused consistent growth of all
      bubbles. With heliox and oxygen breathing, most animals survived during the
      observation period but with air breathing, most animals died of decompression
      sickness regardless of whether the surrounding atmosphere was helium or air. If
      recompression beyond the maximum treatment pressure of oxygen is required, these
      results indicate that a breathing mixture of heliox may be better than air during
      the treatment of decompression sickness following heliox diving.

PMID- 17520863
TI  - Postural control in a simulated saturation dive to 240 msw.
AB  - INTRODUCTION: There is evidence that increased ambient pressure causes an
      increase in postural sway. This article documents postural sway at pressures not
      previously studied and discusses possible mechanisms. METHODS: Eight subjects
      participated in a dry chamber dive to 240 msw (2.5 MPa) saturation pressure. Two
      subjects were excluded due to unilateral caloric weakness before the dive.
      Postural sway was measured on a force platform. The path length described by the
      center of pressure while standing quietly for 60 seconds was used as test
      variable. Tests were repeated 38 times in four conditions: with eyes open or
      closed, while standing on bare platform or on a foam rubber mat. RESULTS: Upon
      reaching 240 msw, one subject reported vertigo, disequilibrium and nausea, and in
      all subjects, mean postural sway increased 26% on bare platform with eyes open (p
      < 0.05) compared to predive values. There was no significant improvement in
      postural sway during the bottom phase, but a trend was seen toward improvement
      when the subjects were standing with eyes closed on foam rubber (p = 0.1).
      Postural sway returned to predive values during the decompression phase.
      DISCUSSION: Postural imbalance during deep diving has been explained previously
      as HPNS possibly including a specific effect on the vestibulo-ocular reflex.
      Although vertigo and imbalance are known to be related to compression rate, this
      study shows that there remains a measurable increase in postural sway throughout
      the bottom phase at 240 msw, which seems to be related to absolute pressure.

PMID- 17520864
TI  - A balancing act--making the right choices in anti-inflammatory drug development.

PMID- 17520865
TI  - Therapeutic benefit of PDE4 inhibitors in inflammatory diseases.
AB  - Intracellular levels of cyclic nuclec tides are closely regulated by distinct
      families of PD Es, which are responsible for the breakdown and degradation of
      cyclic nucleotides within cells. Type 4 PDEs have the potency to modulate the
      release of inflammatory mediators through cAMP-dependent and -independent
      mechanisms. Selective targeting of PDE4 is currently being investigated as a
      novel therapeutic approach in the treatment of inflammation-associated
      respiratory diseases such as asthma and COPD. The development of several PDE4
      inhibitors, including roflumilast and cilomilast, reflects the success of this
      approach. In principle, therapeutic intervention of an inflammatory response by
      PDE4 inhibitors may be extended to other chronic inflammatory disease states such
      as psoriasis, rheumatoid arthritis and inflammatory bowel diseases (e.g., Crohns
      disease and ulcerative colitis). This retiiew explores the feasibility of PDE4
      inhibitors as a promising alternative for therapeutic intervention in systemic
      inflammation and inflammation-based disease.

PMID- 17520866
TI  - Cannabinoids for the treatment of inflammation.
AB  - Cannabinoids are effective at suppressing immune and inflammation functions in
      leukocytes in vitro, and in animal models of acute inflammation, such as the
      mouse hind paw, ear and air pouch models, as well as gastrointestinal, pulmonary,
      myocardial, vascular, periodontal, neural, hepatic, pancreatic and arthritic
      inflammation models. The non-psychoactive cannabinoid receptor CB2 is emerging as
      a critical target for cannabinoid regulation of inflammation, and thus CB2
      selective agonists are undergoing intense investigation and research. This review
      discusses the evidence for cannabinoid regulation of inflammation across a range
      of models and highlights the most promising drug candidates.

PMID- 17520867
TI  - Antirheumatic drugs and gene signatures.
AB  - Rheumatoid arthritis is a chronic autoimmune disease involving progressive
      destruction of the joints. Although a variety of antirheumatic drugs are in use,
      they usually only slow, and not halt, disease progression, or reverse the damage
      to cartilage and bone. Furthermore, treatment has to be discontinued in some
      cases due to toxicity and/or lack of response. By analyzing the whole
      transcriptome of a cell or tissue with microarray technology, a newo way of
      identifying treatments and discovering more about the mechanisms of known drugs
      has become available. This review discusses the strengths and weaknesses of
      microarray technology and gives an overview of gene expression studies currently
      performed in the field of antiheumatic therapies.

PMID- 17520868
TI  - Let the sun shine in: mechanisms and potential for therapeutics in skin
      photodamage.
AB  - Photoaging and photocarcinogenesis are the two Janus faces of skin photodamage.
      Reactivity-based design of prototype agents that antagonize, modulate and reverse
      the chemistry of skin photodamage holds promise in delivering unprecedented
      therapeutic benefit. In contrast to structure-based approaches that use selective
      ligands to target macromolecules, reactivity-based drug discovery uses chemical
      reagents as therapeutics to target reactive chemical species as key mediators of
      skin photo-oxidative stress. The following classes of reactivity-based agents for
      skin photoprotection can be distinguished based on their mechanism of action:
      direct antagonists of photo-oxidative stress (sunscreens, quenchers of photo
      excited states, antioxidants, redox modulators and glycation inhibitors) and skin
      photo-adaptation inducers (nuclear factor erythroid 2-related factor 2 [Nrf2]
      activators, heat-shock response inducers and metallothionein inducers).

PMID- 17520869
TI  - T-cell immune response cDNA 7 in allograft rejection and inflammation.
AB  - The membrane protein T-cell immune response cDNA 7 (TIRC7) is transiently
      expressed in subsets of lymphocytes following antigen stimulation. The importance
      of TIRC7 in immune activation is demonstrated by the effect of antibodies
      directed against extracellular domains of TIRC7. In vitro targeting of TIRC7
      inhibits proliferation and cytokine expression in human, mouse and rat
      lymphocytes, and these inhibitory effects have been associated with induction of
      cytotoxic T-lymphocyte antigen 4 mRNA and protein in the presence of TIRC7
      antibodies. In vivo, anti-TIRC7 antibodies prevent kidney transplant rejection in
      rats and heart allograft rejection in mice. Treatment with an anti-TIRC7 antibody
      as monotherapy or in combination with TNFalpha blockade inhibits disease
      progression in collagen-induced arthritis. TIRC7 expression decreases in the
      peripheral blood of humans who have undergone cardiac transplant prior to
      clinical rejection, and is therefore a promising noninvasive tool for the
      prediction of rejection. Thus, targeting of TIRC7 may lead to the development of
      specific and effective therapeutic and diagnostic approaches by unifying relevant
      cellular and molecular responses in T- and B-cell subsets, and represents a
      promising new pathway for immune regulation in transplantation and autoimmune
      disease.

PMID- 17520870
TI  - PGE synthase inhibitors as an alternative to COX-2 inhibitors.
AB  - NSAIDs and selective COX-2 inhibitors reduce the formation of prostanoids,
      particularly PGE2, to diminish inflammation. However, these drugs exhibit
      toxicities, including gastrointestinal bleeding and myocardial infarction. In
      cells, arachidonic acid is converted to PGE2 by the action of COX enzymes and
      terminal PGE synthase. This review discusses the problems associated with
      selective COX-2 inhibitors and describes the microsomal PGE synthase-1 enzyme,
      its regulation and role in inflammatory diseases, its known inhibitors, and its
      potential as an alternative target for the development of novel anti-inflammatory
      agents.

PMID- 17520871
TI  - Drug evaluation: Pumosetrag for the treatment of irritable bowel syndrome and
      gastroesophageal reflux disease.
AB  - Dynogen Pharmaceuticals Inc, under license from Mitsubishi Pharma Corp, is
      developing pumosetrag (MKC-733, DDP-733), an orally available gastroprokinetic
      agent and locally acting 5-HT3 partial agonist, for the potential treatment of
      irritable bowel syndrome (IBS) with constipation and nocturnal gastroesophageal
      reflux disease (GERD). In September 2005, Dynogen commenced a phase II proof-of
      concept trial of pumosetrag in IBS with constipation; positive results were
      reported in February 2007 and a phase IIb trial was to start in the fourth
      quarter of 2007. In September 2006, the company had initiated a phase Ib trial in
      nocturnal GERD.

PMID- 17520872
TI  - Drug evaluation: TA-2711E in the treatment of active distal ulcerative colitis.
AB  - Tanabe AAI LLC, a joint venture between Tanabe Seiyaku Co. Ltd. and aaiPharma
      Inc., is developing TA-2711E, an enema formulation of Tanabe's mucosal protectant
      ecabet, for the potential treatment of ulcerative colitis. By July 2004, phase
      III trials for ulcerative colitis had been initiated in Japan and phase II
      studies were ongoing in Europe and the U.S.; this remained the case in May 2006.

PMID- 17520873
TI  - Characteristics of births to single- and multiple-race women: California, Hawaii,
      Pennsylvania, Utah, and Washington, 2003.
AB  - OBJECTIVES: In 2003, California, Hawaii, Pennsylvania, Ohio (for births occurring
      in December only), Utah, and Washington provided to the National Center for
      Health Statistics (NCHS) multiple as well as single racial entries that mothers
      and fathers had reported on birth certificates in accordance with the revised
      race and ethnicity standards issued by the Office of Management and Budget (OMB)
      in 1997. This report provides detailed data on women reporting single race (one
      race) and multiple race (two or more races) by selected demographic and health
      characteristics (e.g., fertility, age at first birth, Hispanic ethnicity, marital
      status, country of birth, preterm birth, and low birthweight) of the women and
      their infants. Data presented in this report are derived from birth certificates
      from the five states that collected, reported, and transmitted to NCHS multiple
      race data as of January 1, 2003 (California, Hawaii, Pennsylvania, Utah, and
      Washington). Data on selected demographic and health characteristics were
      analyzed comparing single-race mothers to multiple-race mothers. METHODS:
      Descriptive tabulations of data reported on the birth certificates of the single-
      and multiple-race births that occurred in the reporting area in 2003 are
      presented. RESULTS: In 2003, 2.5 percent of births in California, Hawaii,
      Pennsylvania, Utah, and Washington were to women who reported two or more races,
      with levels varying from 1 (Utah) to 33 percent (Hawaii). Birth and fertility
      rates for single-race (one race) groups were generally lower than the rates for
      multiple-race groups (each race in combination with one or more other races),
      whereas age at first birth was generally higher for single-race women than for
      multiple-race women. The percentages of Hispanic births to single-race black,
      American Indian or Alaska Native (AIAN), Asian, and Native Hawaiian or Other
      Pacific Islander (NHOPI) women were lower than the percentage for women reporting
      those races in combination with one or more of the other races (multiple race).
      The percentage of births to unmarried women was higher among single-race black
      and AIAN women compared with multiple-race black and AIAN women, whereas the
      proportions were considerably higher for multiple-race white, Asian, and NHOPI
      women than for their single-race counterparts. The percentage of mothers born in
      the 50 states and the District of Columbia was consistently higher for multiple
      race women than single-race women. In terms of infant health characteristics,
      infants of single-race white and Asian women had a lower preterm birth rate than
      infants of multiple-race white and Asian women, whereas infants of single-race
      black and AIAN women had higher preterm rates than infants of multiple-race black
      and AIAN women. The low birthweight rate was also significantly lower for single
      race white, Asian, and NHOPI women than their multiple-race counterparts. In
      comparison, the rate for single-race black women was higher than the rate for
      multiple-race black women.

PMID- 17520874
TI  - VA Tech disaster response shows value of drills, planning.
AB  - Full-scale, tabletop exercises prove effective predictors of how events unfolded
      Color-coded triage tags, implemented in the field, smooth the way for treatment
      in the ED. Communication becomes an issue as cell phones go down all over the
      community.

PMID- 17520875
TI  - PSO: an evolving, critical role in health care quality.
AB  - PSO must be educator, diplomat, analyst, student, negotiator, and communicator.
      Experts say position should not be linked with other job responsibilities.
      Passion for patients, strong leadership skills are keys to success.

PMID- 17520876
TI  - Panel lays a framework for ethical conduct in QI.
AB  - Quality improvement seen as intrinsic part of healthcare operations. Patients as
      well as QI professionals have ethical obligations. Research framework creates too
      much rigidity for most QI projects.

PMID- 17520877
TI  - Don't have an ICU? you can still have an RRT.
AB  - Insufficient staffing, need for physician coverage of the rapid response team,
      other reasons for alternate models. ED and ICU nurses can be cross-trained to
      cover each other's units and the RRT. EMS staff can also be used, especially when
      many also are RNs.

PMID- 17520878
TI  - Data reveal 90% of ADEs not administration errors.
AB  - Average total hospital costs for patients who experienced ADE's 50% more than for
      those who didn't. Corticosteroids, blood thinners, and anti-cancer drugs are meds
      most often involved with ADEs. Monitoring of anti-coagulants should be regular
      and frequent to ensure they are having the desired effect.

PMID- 17520879
TI  - [Precancerous gastric diseases].
AB  - The paper presents statistical data on gastric cancer (GC) incidence. Pre
      cancerous conditions in the stomach (polyps, peptic ulcer, post-resection
      syndromes, chronic atrophic gastritis) are considered in detail. The author
      evaluates the role played by Helicobacter pylori persistence in gastric cancer
      pathogenesis, and discloses the genetic aspects of oncogenesis. The modern
      conception of gastrocarcinogenesis, based upon the multicasuality and a multi
      factor character of endogenious impacts on the gastric glandular apparatus, is
      described in the article. Preventive measures should be taken with consideration
      of this approach and include individual and social preventive measures.

PMID- 17520880
TI  - [Chronic pancreatitis: the modern state of the problem. Part 2. Clinical
      manifestations, diagnostics, classification, and the principles of treatment].
AB  - The review presents the latest data on the epidemiology of chronic pancreatitis
      (CP), its etiology and pathogenesis, and the modern classification of the
      disease. The review supports the great diversity of etiological factors of CP,
      which determine peculiarities of its pathogenesis and clinical picture.

PMID- 17520881
TI  - [Comparison of the results of coronary angioplasty and stenting during one year
      following surgery].
AB  - The purpose of the study was to compare long-term results of angioplasty and
      coronary arterial stenting (CAS) depending on the initial degree of coronary
      arterial (CA) lesion according to morphological stenosis classification, as well
      as to evaluate the influence of re-stenosis on myocardial contractility dynamics,
      anginal recurrence rate, and exercise tolerance. The subjects, 228 men after
      angioplasty and 184 men after CAS with wire stents without drug coating, were
      included in the study between 1989 and 2005. Coronarography was repeated in 358
      patients one year after surgery. The patients were divided into two groups. The
      first group consisted of 161 patients, to who 180 stents were implanted. The
      second group consisted of 197patients, in who 226 angioplasty procedures were
      performed. Data were processed using standard variational statistical methods,
      i.e. the calculation of mean values and standard deviation. Statistical
      calculations were carried out using Analysis ToolPak- VBA software of Microsoft
      Excel 2000. The study found that one year after either intervention the number of
      patients without anginal symptoms fell significantly compared with this number
      during the in-hospital period. In group 2 the frequency of restenosis was higher
      and the number of patients with anginal symptoms was significantly bigger than in
      group 1; the number of asymptomatic patients was significantly bigger in group 1.
      Initial morphological characteristics of CA lesion had a significant effect on
      the long-term frequency of restenosis following endovascular treatment.
      Restenosis was 2 to 2.5 times more frequent in patients with C type CA lesion vs.
      patients with A type regardless the method of endovascular intervention. The
      results of the study demonstrate the importance of taking into account initial
      morphological characteristics of CA lesion; CAS is more preferable than
      angioplasty, especially in patients with C type CA lesion.

PMID- 17520882
TI  - [Evaluation of the degree of respiratory failure in patients with chronic
      obstructive pulmonary disease].
AB  - Thirty practically healthy individuals and 111 patients suffering from chronic
      obstructive pulmonary disease (COPD) with I to III degree chronic respiratory
      failure (CRF) were examined. The study established a negative correlation between
      partial oxygen pressure in arterial blood (AB), the degree of bronchial
      obstruction, hemoglobin saturation, and the degree of CRF. It was found that the
      degree of CRF was in a significant correlation with the degree of pulmonary
      physiological (alveolar) shunt and the degree of hypercapnia. The author proposes
      an algorithm for precise determination of the degree of CRF that includes
      calculation of alveolar shunt as an integral parameter reflecting the degree of
      AB gas changes.

PMID- 17520883
TI  - [The myocardial condition in chronic obstructive pulmonary disease and bronchial
      asthma].
AB  - The purpose of the study was to assess the influence of structural and functional
      changes in the myocardium of the right and left ventricle (RVand LV) on the
      development of ischemia and arrhythmia in chronic obstructive pulmonary disease
      (COPD) and bronchial asthma (BA). The subjects of the study were 156 patients
      with either persistent BA (81 patients) or COPD (75 patients). Patients with
      decompensated cor pulmonale were excluded. ECG, 24-hour ECG monitoring, and
      echocardioscopy were performed. The study found that the occurrence of
      supraventricular and ventricular extrasystoles (SVES and VES) in patients with
      mild COPD or BA depended on the condition of RV diastolic function and on LV
      diastolic function and myocardial ischemia as well in COPD. In moderate BA the
      processes of myocardial remodeling correlate with myocardial ischemia, RV
      dysfunction and increased pulmonary arterial pressure (PAP), as well as with
      lipid dismetabolism. The appearance of SVES in patients with severe BA is
      connected with interventricular septal hypertrophy, LV dysfunction, and increased
      PAP, while VEC appear due to myocardial ischemia and hypercholesterolemia. In
      severe COPD the occurrence of SVES and VES does not depend on structural and
      functional changes in the myocardium, while myocardial ischemia is connected with
      LV hypertrophy. In BA ischemia depends on the development of RV and LV diastolic
      dysfunction, as well as hypercholesterolemia.

PMID- 17520884
TI  - [Factors influencing left ventricular diastolic function in elderly patients with
      chronic heart failure].
AB  - The purpose of the study was to define factors influencing the diastolic left
      ventricular (LV) function in elderly patients with chronic heart failure (CHF).
      Ninety-seven I to IV functional class CHF patients aged 65 to 88 (mean age 76.6+/
      5.1 yr), 61 women and 36 men, were examined. CHF was caused by coronary artery
      disease in 22 (22.7%) patients, by arterial hypertension in 14 (14.4%) patients,
      and by both in 61 (62.9%) patients. Fourteen (14.4%) patients had type 2
      diabetes. Hemoglobin level lower than 130g/l in men or 120g/l in women was
      considered anemia. Glomerular filtration speed (GFS) was calculated using
      Cockcroft-Gault formula. EchoCG and Doppler EchoCG were performed in all
      patients. LV hypertrophy (LVH) was revealed in 90 (92%) of the patients;
      52patients had concentric L VH and 38 patients had eccentric LVH. Ejection
      fraction was less than 45% in 17 (17.5%) patients. Isovolemic relaxation time
      (IVRT) was over the normal limit in 73 (75.3%) patients; the time of early
      diastolic flow slowing (DT) changed in different directions and was 211.2+/-55.6
      msec. A type of transmitral blood flow with relaxation disorder was found in 58
      (59.8%) patients, a pseudonormal type was revealed in 32 (33%), and a restrictive
      type was found in 7 (7.2%) of patients. The study found a reverse independent
      correlation between hemoglobin level and the speed of LV filling during atrial
      systole. An independent correlation between the degree of renal dysfunction (GFS)
      and disorder of LV relaxation was found: the lower GFS, the longer IVRT and DT.
      Thus, in addition to age and structural changes in the heart, factors that have
      adverse effects on diastolic filling parameters are anemia, lowered renal
      function, and the level of systolic and diastolic pressure.

PMID- 17520885
TI  - [Evaluation of the risk of atrial fibrillation using disperse analysis of P in
      ECG].
AB  - The aim of the study was to find new ECG markers of atrial fibrillation (AF)
      risk. The clinico-functional status of 371 patients was studied using standard 12
      lead ECG. According to 24-hour monitoring, 190 (51.2%) patients had AF, while 181
      (48.8%) patients did not. The groups were age- and gender-comparable. The study
      demonstrated low significance of P elongation in standard lead II in the two
      groups (15.3% and 18.8% of cases, respectively) and Macrus index (18.9% and 17.
      7%, respectively). At the same time, the minimum P length in all 12 leads was
      significantly lower in patients with AF (an average of 63.28 and 70.05 msec,
      respectively, p < 0. 05). The most significant differences were observed in the
      values of normalized P length (an average of 15.68 and 29.50 msec, respectively,
      p < 0.05) and P dispersion (an average of 51.28 and 42.39 msec, p < 0.05). The
      study found certain peculiarities of the dynamics of these parameters in
      correlation with a growth of AF frequency, as well as the importance of their
      correlation with the presence of heart failure and stable stenocardia. The
      authors presume that new markers of AF risk should be evaluated through disperse
      analysis of standard ECG registered in 12 standard leads.

PMID- 17520886
TI  - [The mechanism of reverse cholesterol transport and cholelithiasis in Northern
      ethnic groups].
AB  - The aim of the study was to investigate metabolic factors that protect the human
      organism from cholelithiasis and coronary artery disease (CAD). An
      epidemiological study was carried out to determine the prevalence of
      cholelithiasis and CAD in eight settlements of Yakutia and Evenkia. The subjects
      were 1154 Evens and Evenks, and 1591 Europoids. The parameters under study were
      the lipid composition and bile acid (BA) spectrum as well as the level of lipids,
      the spectrum of lipoproteins, neutral lipids, and phospholipids in the serum and
      blood plasma. Among Europoids, the prevalence of cholelithiasis was 8.8%, and the
      prevalence of CAD was 18.8%, while among Mongoloids they were 1.5% (p < 0.001)
      and 10.2% (p < 0.001), respectively. Serum levels of total cholesterol (CH) were
      significantly higher in Europoids than in Evens and Evenks, whereas CH, BA, and
      primary cholates prevailed in bile of Mongoloids. The levels of main LCHAT
      reactive substrates evidence a significantly higher efficiency of CH
      esterification in Evens and Evenks vs. Europoids. Highly effective mechanism of
      CH return transport, an important component of which is active BA synthesis and
      transport of sterins into bile should be considered the leading factor that
      protects high latitude Mongoloids from cholelithiasis and CAD.

PMID- 17520887
TI  - [The prognosis and risk factors of cardiovascular complications in patients with
      chronic glomerulonephritis].
AB  - The authors evaluated 10-year prognosis according to SCORE scale and risk factors
      of fatal cardiovascular diseases in 90 Eropoids aged 53.9+/-0.6 years with a
      valid diagnosis of chronic glomerulonephritis (CGN) and normal renal function or
      at the pre-dialysis stage of chronic renal failure. The study found that 34.4% of
      CGN patients were at high risk of severe complications of atherosclerosis with
      unfavorable prognosis (myocardial infarctions, cerebral stroke etc.) The leading
      risk factors of fatal cardiovascular complications in middle-age and elderly CGN
      patients were male sex, age more than 55 years, smoking, and severe systolic and
      diastolic arterial hypertension. Patients with IIb phenotype hyperlipidemia and
      those with selective decrease in high density lipoprotein cholesterol are at
      significantly higher risk of cardiovascular events.

PMID- 17520888
TI  - [The influence of 3-oxypyridine antioxidants on depression in patients with
      diabetes mellitus].
AB  - The authors studied the influence of 3-oxypyridine derivates (emoxypine and
      mexidol) on the degree of depressive symptoms in patients with diabetes mellitus;
      the data were matched with the dynamics of blood lipoperoxidation. The study
      found that administration of emoxypine (150 mg every day) or mexidol (300 mg a
      day) during 14 days lowered the level of circulating lipoperoxidation products
      and diminished manifestations of depression, which was accompanied by improvement
      in cognitive functions and quality of life; the degree of the changes was
      similar. These clinical effects of 3-oxypyridine derivates were independent of
      the dynamics of glycemia and lipidemia.

PMID- 17520889
TI  - [Rabeprazole test and comparison of the effectiveness of course treatment with
      rabeprazole in patients with gastroesophageal reflux disease and non-coronary
      chest pain].
AB  - Proton pump inhibitors (PPI) are efficient for ex juvantibus diagnostics of non
      coronary chest pain (NCCP) of gastroesophageal reflux origin as well as for its
      course treatment. The aim of this randomized cross-over study was to compare the
      efficiency of rabeprasol and omeprasol as means of both diagnostics and long-term
      treatment. In rabeprasol group the symptoms disappeared more quickly, and the
      maximum effect was achieved by day three, while in omeprasol group the best
      results were achieved only by day six (p < or = 0.05). The sensitivity and
      specificity of rabeprasol test was 81.6% and 80.6%, respectively, while those of
      omeprasol test were 73.5% and 77.4%, respectively. By the end of the 12th week of
      treatment pain syndrome had been completely or partly coped with in 92% of
      rabeprasol patients, and 76% of omeprazol patients (p < 0.05). Thus, response to
      rabeprasol takes place twice as quick as response to omeprasol, which makes it
      possible to shorten the time of NCCP diagnostics. Furthermore, rabeprasol test is
      more sensitive and specific. Course treatment with high doses of PPI increase the
      number of patients with eliminated pain syndrome, and rabeprasol here is more
      efficient than omeprasol.

PMID- 17520890
TI  - [Stress-dependent lesions of the gastroduodenal mucosa during operations with
      cardiopulmonary bypass].
AB  - A continuous retrospective study was conducted in order to reveal risk factors
      and optimal ways of prophylaxis of gastroduodenal hemorrhage after operations
      with cardiopulmonary bypass. All the 559 cases operated on with cardiopulmonary
      bypass in Department of Cardiosurgery of Omsk Regional Clinical Hospital between
      January 2003 and December 2005 were analyzed. Risk factors and the effectiveness
      of different methods of antisecretory prophylaxis of hemorrhage were evaluated.
      It was found that the frequency of postoperative gastroduodenal hemorrhage was
      influenced by the degree of circulatory insufficiency, duration of artificial
      lung ventilation, cardiopulmonary bypass, and aortal occlusion, as well as
      application of anticoagulants and the frequency of gastric and duodenal erosions
      or ulcers prior to operation. The most effective means of prophylaxis was
      omeprazole administered intravenously during three days followed by oral
      application during three weeks. A short course of H2-histamine blockers
      discontinued abruptly increased hemorrhage-related lethality in this group of
      patients due to withdrawal syndrome.

PMID- 17520891
TI  - [Characterization of persons recognized as disabled due to diabetes mellitus for
      the first time].

PMID- 17520892
TI  - [Present-day problems of clinical pharmacogenetics].
AB  - The authors deal with the problem of clinical introduction of pharmacogenetic
      studies to individualize pharmacotherapy. On the basis of their own studies they
      propose the methodology of studying the clinical significance of pharmacogenetic
      studies of biotransformation system and drug transporters, and formulate the main
      requirements pharmacogenetic studies should meet to be introduced to clinical
      practice.

PMID- 17520893
TI  - [A clinicoeconomic model of basic therapy for bronchial asthma].
AB  - The paper is dedicated to analysis of the most wide-spread variants of bronchial
      asthma (BA) basic therapy. The analysis was based on the results of a large (1362
      patients from 34 Russian cities) pharmacoepidemiological study. Different models
      of pharmacotherapy were assessed on the basis of clinical data (the frequency of
      symptoms), the risk of BA exacerbation, the volume of public health resources
      used, and the cost of treatment. The results of the study showed that the use of
      set combinations of inhaled glucocorticosteroids and long-acting , beta2
      adrenostimulators was most effective and rational from economic perspective under
      real clinical conditions.

PMID- 17520894
TI  - [Acute myocarditis caused by ECHO virus].
AB  - Enteroviral infection is characterized by clinical polymorphism. One of its
      clinical manifestation is myocarditis, which is usually caused by Coxsackie
      virus. ECHO viruses cause the disease mostly in childhood. The article presents a
      case of enteroviral (ECHO) infection complicated by pneumonia and focal
      myocarditis in a 41-year-old patient, hospitalized during a season of influenza
      and acute respiratory infections. Acute myocarditis was moderate and the patient
      recovered by day 23.

PMID- 17520895
TI  - [Collagenous sprue: a case description].
AB  - Collagenous sprue (CS) is a rare disease of the small bowel, which is
      characterized by complete atrophy of mucosal villi and excessive subepithelial
      collagen deposition. The authors describe a 40-year-old patient, who was examined
      for severe malabsorption syndrome. The diagnosis of celiac disease was based upon
      serological and histological data, but gluten-free diet was not effective and
      only treatment with prednisolone led to positive changes. Another histologic
      study revealed a focal deposit of collagen under the epithelium in addition to
      signs of intestinal mucosal atrophy, and the diagnosis of CS was made. The case
      is discussed from the positions of known information of CS.

PMID- 17520896
TI  - [Forensic medical assessment of subendocardial hemorrhage in acute blood loss].
AB  - A retrospective analysis of forensic autopsy protocols for 240 victims who died
      of acute blood loss aged 17-55 years (186 male and 56 female corpses--76.8 and
      23.2%, respectively) has shown that appearance of Minakov's spots (MS) depends on
      duration of the terminal period. Subendocardial hemorrhages occurred most
      frequently (61.5%) in the terminal period up to one hour. The terminal period for
      several minutes was associated with MS appearance in 27.5% cases, for several
      hours--in 6.6%, for 24 hours and more--in 4.4%. MS incidence rate did not
      correlate with the group of the study, blood loss volume, severity of alcohol
      intoxication.

PMID- 17520897
TI  - [New criteria of inflammatory-reparative processes in the region of splenic
      injury caused by blunt objects].
AB  - We propose new criteria of healing of splenic injuries. Such criteria allow a
      detailed follow-up of the inflammatory-reparative process. We have developed an
      evaluation table. In forensic-histological study the table facilitates and
      specifies timing of splenic blunt injury.

PMID- 17520898
TI  - [Evaluation of hair injuries depending on properties of impact surface of a blunt
      object and impact conditions].
AB  - We investigated injured hair on crime instruments and head wounds. The findings
      were confirmed in experiments. Morphological characteristics of hair damage were
      associated with properties of an impact surface and conditions of the traumas. We
      propose a new method of registration of blunt head injury. Diagnostic criteria of
      hair injuries to identify crime instruments and to determine trauma mechanisms
      are demonstrated.

PMID- 17520899
TI  - [Identification of sperm on the spots located on material evidences using solid
      phase enzyme immunoassay with human prostate-specific antigen].
AB  - It is shown that for verification of human sperm presence on the spots on
      material evidence it is feasible to apply solid phase enzyme immunoassay (EIA)
      with the kit "PSA-EIA-BEST T-8458" which is used in clinical practice for
      diagnosis of prostatic cancer and some other diseases. The method is specific and
      highly sensitive, convenient for objective registration and computer processing.
      It is also cost-effective and provides not only significant identification of
      sperm on the exhibits but also its human origin in complete absence of
      spermatozoa on the spot.

PMID- 17520900
TI  - [Diagnosis of acute intoxication with ethyl alcohol in expert practice].
AB  - Significant chemical and biochemical signs of acute alcoholic intoxication are
      considered tanatologically. A complex approach to diagnosis of acute poisoning
      with ethyl alcohol is proposed.

PMID- 17520901
TI  - [Approaches to setting up the Center for identification of exhumed bodies in
      Chechen Republic].
AB  - The authors participated in the activity of a group of European experts who
      visited Moscow, Rostov-on-Don and Grozny in September 2005 to clarify situation
      with identification of exhumed unknown dead bodies of the civil population. The
      European experts recommend to set up Center for Identification in Chechen
      Republic (in Grozny). The authors propose to make DNA identification tests in the
      Russian Federation Center for Forensic Medical Evaluation in Moscow which has
      much experience and staff skilled in identification of unknown exhumed bodies and
      can solve the problem of genetic identification of unidentified bodies of people
      missed in the Chechen Republic more effectively.

PMID- 17520902
TI  - [Development and application of hydrogel oligonucleotide microchips for forensic
      medical personal identification as illustrated by ABO locus].
AB  - The article describes the method defining 5 alleles of ABO blood group typing
      system by molecular hybridization in hydrogel oligonucleotide microchip. The
      testing points were SNP variants in positions 261 and 297of exon 6 and in
      positions 646 and 657 of exon 7. Therefore, 5 ABO blood groups can be easily
      revealed: A, B, 0(1), 0(1v), 0(2). The method was tested on 10 DNA samples
      isolated from blood and saliva of unrelated individuals. The results were
      confirmed by sequencing of the identified allelic fragments. Estimation
      sensitivity was 25 pg of total DNA input. This technique is cost-effective and
      easy for use and, therefore, promising for forensic-medical personal
      identification.

PMID- 17520903
TI  - [Insertion of chemical elements into knitted fabrics in cases of using traumatic
      gas guns with rubber bullets].
AB  - Roentgenofluorescent spectrometry was used for identification of chemical
      elements and their quantitation in the zones of damage to different knitted
      fabrics done by shots from traumatic gas gun with rubber bullets.

PMID- 17520904
TI  - [Current approaches to analysis of narcotic drugs in biological substances].
AB  - A method of analysis of basic narcotic drugs in urine is described. It consists
      in isolation by solid phase extraction, derivation and identification by gas
      chromatography with mass-selective detector. The approaches applied in the above
      method can be used for analysis of narcotic drugs undetectable by preliminary
      investigations as well as for urine examination for pharmacological or other
      biologically active substances.

PMID- 17520905
TI  - [Application of extraction freezing for analysis of 1,4-benzodiazepines in
      urine].
AB  - A test for 1,4-benzodiazepines in urine is described. Extraction and freezing
      were used at the stage of the sample preparation. Metrological characteristics of
      the method are presented. Selectivity of the test is provided by optimal
      conditions for high-performance liquid chromatography. The technique is simple to
      use and cost-effective.

PMID- 17520906
TI  - [Detection of azaleptine in forensic chemical examination of cadaveric material].
AB  - Azaleptine detection and quantitation in cadaveric material in forensic-chemical
      tests using thin-layer chromatography, UV-spectrophotometry, gas chromatography
      mass spectrometry are outlined.

PMID- 17520907
TI  - [Metalloligand homeostasis: molecular basis of iatrogenic and technogenic trace
      element deficiency].
AB  - It is well known that a toxic effect of some medicines is the result of their in
      vivo interactions with trace elements leading to disturbance of trace element
      balance in the living body. The Mossbauer spectrometry technique has been used
      for toxicochemical evaluation of iron-bearing medicines. This method can be used
      in forensic toxicology. We studied composition of trace elements in the hair of
      children living in Macedonia: in polluted territory (the town of Veles, the study
      group) versus in unpolluted one (Ivankovci village, the control group). AES-ICP
      and ICP-MS techniques were used. We discovered that the hair of children living
      in the polluted territory contain significantly elevated concentrations of Pb (in
      43% cases), Hg, Ni (14%), Cd (21%), Cu (16%), Sn, As, Na, Se and subnormal
      concentrations of Mg (in 51% cases), Mn, Cr and Li.

PMID- 17520908
TI  - [Strangulation of the noose put around the neck and pulled tight with own hands
      of the victim without fixing devices as a variant of suicide].

PMID- 17520909
TI  - [Some characteristics in establishment of cause-effect relations between injuries
      and their consequences during patient medical care].

PMID- 17520910
TI  - [History of one examination on forensic medicine].

PMID- 17520911
TI  - [Laboratory provision of primary health care facilities: the Federal external
      quality assessment system data].

PMID- 17520912
TI  - [The assurance and control of the quality of laboratory studies in primary health
      care].

PMID- 17520913
TI  - [Assessment of the quality of laboratory studies at clinical diagnostic
      laboratories of local hospitals and ambulance stations].

PMID- 17520914
TI  - [The quality indices of hermatological studies in the public health system of the
      Russian Federation: the Federal external quality assessment system data].

PMID- 17520915
TI  - [Catecholamines: biosynthesis (a lecture)].

PMID- 17520916
TI  - [Some aspects of quality control of hematological analyzers].

PMID- 17520917
TI  - [Experience with hematological analyzers at clinical diagnostic laboratories].

PMID- 17520918
TI  - [Errors during enzyme immunoassay].

PMID- 17520919
TI  - [Activities within the framework of the National "Health" project in the North
      Westernal Federal District].

PMID- 17520920
TI  - [Results of the participation of 360 laboratories of Russia in the external
      quality assessment program for HBsAG tests].
AB  - During their first participation in the external quality assessment program
      (EQAP), 78-81% of the laboratories detect positive samples of control panels
      containing 0.125 IU/ml of HBsAg; 95-97% of them identify negative samples of the
      control panels. The high efficiency of EQAP was established when the results of
      the same laboratories that had participated in two cycles were compared. For
      correct detection of positive samples of the control panel, it is necessary to
      use disposable containers and tips for example for solutions of conjugate
      concentrate, tetramethylbenzidine, buffer for conjugate dilution, and citrate
      phosphate solution. The ranges of 95% confidence interval were established for
      the individual values of CV values of the commercial preparation ILC-HBsAg in the
      laboratories: from 0 to 11.3% with estimated convergence and from 0 to 14.2% with
      estimated reproducibility. In making an intralaboratory control of the quality of
      HBsAg test using ILC-HBsAg, one should be guided by the test accuracy indices
      given in the application sheet.

PMID- 17520921
TI  - [Laboratory components of health care standards (extracts from the health care
      standards approved by the orders of the Ministry of Health and Social Development
      of the Russian Federation)].

PMID- 17520922
TI  - The MARE research program 1999-2006: reflections on program management.

PMID- 17520923
TI  - The Finnish Baltic Sea Research Programme (BIREME).

PMID- 17520924
TI  - Modeling riverine nutrient transport to the Baltic Sea: a large-scale approach.
AB  - We developed for the first time a catchment model simulating simultaneously the
      nutrient land-sea fluxes from all 105 major watersheds within the Baltic Sea
      drainage area. A consistent modeling approach to all these major watersheds,
      i.e., a consistent handling of water fluxes (hydrological simulations) and
      loading functions (emission data), will facilitate a comparison of riverine
      nutrient transport between Baltic Sea subbasins that differ substantially. Hot
      spots of riverine emissions, such as from the rivers Vistula, Oder, and Daugava
      or from the Danish coast, can be easily demonstrated and the comparison between
      these hot spots, and the relatively unperturbed rivers in the northern catchments
      show decisionmakers where remedial actions are most effective to improve the
      environmental state of the Baltic Sea, and, secondly, what percentage reduction
      of riverine nutrient loads is possible. The relative difference between measured
      and simulated fluxes during the validation period was generally small. The
      cumulative deviation (i.e., relative bias) [Sigma(Simulated - Measured)/Sigma
      Measured x 100 (%)] from monitored water and nutrient fluxes amounted to +8.2%
      for runoff, to -2.4% for dissolved inorganic nitrogen, to +5.1% for total
      nitrogen, to +13% for dissolved inorganic phosphorus and to +19% for total
      phosphorus. Moreover, the model suggests that point sources for total phosphorus
      compiled by existing pollution load compilations are underestimated because of
      inconsistencies in calculating effluent loads from municipalities.

PMID- 17520925
TI  - Denitrification in the river estuaries of the northern Baltic Sea.
AB  - Estuaries have been suggested to have an important role in reducing the nitrogen
      load transported to the sea. We measured denitrification rates in six estuaries
      of the northern Baltic Sea. Four of them were river mouths in the Bothnian Bay
      (northern Gulf of Bothnia), and two were estuary bays, one in the Archipelago Sea
      (southern Gulf of Bothnia) and the other in the Gulf of Finland. Denitrification
      rates in the four river mouths varied between 330 and 905 micromol N m(-2) d(-1).
      The estuary bays at the Archipelago Sea and the Gulf of Bothnia had
      denitrification rates from 90 micromol N m(-2) d(-1) to 910 micromol N m(-2) d(
      1) and from 230 micromol N m(-2) d(-1) to 320 micromol N m(-2) d(-1),
      respectively. Denitrification removed 3.6-9.0% of the total nitrogen loading in
      the river mouths and in the estuary bay in the Gulf of Finland, where the
      residence times were short. In the estuary bay with a long residence time, in the
      Archipelago Sea, up to 4.5% of nitrate loading and 19% of nitrogen loading were
      removed before entering the sea. According to our results, the sediments of the
      fast-flowing rivers and the estuary areas with short residence times have a
      limited capacity to reduce the nitrogen load to the Baltic Sea.

PMID- 17520926
TI  - Modeling the Baltic Sea eutrophication in a decision support system.
AB  - SANBALTS (Simple As Necessary Baltic Long-Term Large-Scale) is a model of the
      coupled nitrogen and phosphorus cycles. This model has been developed as an
      integral part of the decision support system Marine Research on Eutrophication's
      Nest with the overall aim to evaluate management options for reducing Baltic Sea
      eutrophication. Simulated nutrient and oxygen concentrations as well as transport
      flows and major biogeochemical fluxes can be analyzed in many different ways,
      including construction of detailed nutrient budgets and tracing the fate of
      nutrient inputs. The large amounts of data that exist for this sea makes it
      possible to validate model results with observations. Major biogeochemical
      properties of the Baltic Sea are discussed through an analyses of model
      sensitivity to external forcing and internal parameterizations. Model results
      emphasize two features that are especially important for ecosystem management: i)
      impacts of local measures would always be modified by the long-range transports
      from other regions and ii) the response to significant changes in loads would
      only be seen after several decades.

PMID- 17520927
TI  - Role of sea-ice biota in nutrient and organic material cycles in the northern
      Baltic Sea.
AB  - This paper compiles biological and chemical sea-ice data from three areas of the
      Baltic Sea: the Bothnian Bay (Hailuoto, Finland), the Bothnian Sea (Norrby,
      Sweden), and the Gulf of Finland (Tvarminne, Finland). The data consist mainly of
      field measurements and experiments conducted during the BIREME project from 2003
      to 2006, supplemented with relevant published data. Our main focus was to analyze
      whether the biological activity in Baltic Sea sea-ice shows clear regional
      variability. Sea-ice in the Bothnian Bay has low chlorophyll a concentrations,
      and the bacterial turnover rates are low. However, we have sampled mainly land
      fast level first-year sea-ice and apparently missed the most active biological
      system, which may reside in deformed ice (such as ice ridges). Our limited data
      set shows high concentrations of algae in keel blocks and keel block interstitial
      water under the consolidated layer of the pressure ridges in the northernmost
      part of the Baltic Sea. In land-fast level sea-ice in the Bothnian Sea and the
      Gulf of Finland, the lowermost layer appears to be the center of biological
      activity, though elevated biomasses can also be found occasionally in the top and
      interior parts of the ice. Ice algae are light limited during periods of snow
      cover, and phosphate is generally the limiting nutrient for ice bottom algae.
      Bacterial growth is evidently controlled by the production of labile dissolved
      organic matter by algae because low growth rates were recorded in the Bothnian
      Bay with high concentrations of allochthonous dissolved organic matter. Bacterial
      communities in the Bothnian Sea and the Gulf of Finland show high turnover rates,
      and activities comparable with those of open water communities during plankton
      blooms, which implies that sea-ice bacterial communities have high capacity to
      process matter during the winter period.

PMID- 17520928
TI  - Impacts of eutrophication on diatom life forms and species richness in coastal
      waters of the Baltic Sea.
AB  - Increased nutrient and sediment loading can affect the functioning and
      biodiversity of coastal ecosystems. Lacking long-term monitoring data,
      paleolimnological techniques enable the estimation of habitat and diversity
      change through time. Using these methods we assessed the effects of
      eutrophication on diatom community structure and species richness over the past
      ca. 200 years in coastal waters of the Gulf of Finland. The abundance of
      planktonic diatoms has increased markedly because of increased eutrophication and
      turbidity. The loss of benthic habitats resulted in a clear decrease in diatom
      species richness after a threshold of 400-600 microg L(-1) total dissolved
      nitrogen; no unimodal pattern between diversity and productivity was observed in
      our data. The urban sites displayed a marked decrease in species richness
      starting in the late 19th century with increased urbanization. A clear recovery
      was visible after the cessation of point source loading by the mid-1980s at two
      sites, whereas at the third site no recovery was detected because of diffuse
      loading from the large catchment. Changes in the rural sites were minor and did
      not start until the 1940s.

PMID- 17520929
TI  - The impact of benthic macrofauna for nutrient fluxes from Baltic Sea sediments.
AB  - This article focuses on the ecological role of benthic macrofauna on nutrient
      dynamics and benthic-pelagic coupling in the Baltic Sea with relation to
      eutrophication. Generally, benthic macrofaunal activities have large effects on
      sediment biogeochemistry and often with stimulatory effects on processes that
      counteract eutrophication, i.e., denitrification and increased phosphorus
      retention of the sediment. The degree of faunal impact on such processes varies
      depending on faunal density and functional group composition. The effect of
      macrofaunal activities on sediment nutrient dynamics can also result in a higher
      nitrogen: phosporus ratio of the sediments efflux compared with sediments without
      macrofauna. Increased internal nutrient loading during eutrophication-induced
      anoxia is suggested to be caused both by altered sediment biogeochemical
      processes and through reduced or lost bioturbating macrofauna and thereby a
      reduced stimulatory effect from their activities on natural purification
      processes of the Baltic Sea ecosystem.

PMID- 17520930
TI  - M74 syndrome in Baltic salmon and the possible role of oxidative stresses in its
      development: present knowledge and perspectives for future studies.
AB  - Baltic salmon suffer from maternally transmitted yolk-sac fry mortality syndrome-
      M74. The incidence of M74 varies considerably on a year to year basis. In the
      1990s the mortalities were 50-80% but in 2003-2005, below 10%. Before death, M74
      affected fry have several typical symptoms. M74-eggs are characterized by low
      thiamine and carotenoid content, and affected fry show signs of oxidative stress.
      Although M74 is associated with thiamine deficiency and the symptoms of the fry
      can be alleviated with thiamine, the underlying causes of the syndrome have
      remained a mystery. We have studied the symptoms of M74 at the molecular level by
      investigating the global gene expression patterns using cDNA microarray and have
      quantified the changes in transcriptional regulation in M74-affected and healthy
      yolk-sac fry. Our and previous results suggest that M74 in Baltic salmon yolk-sac
      fry results from oxidative stresses disturbing several different developmental
      molecular pathways. Because the M74 syndrome is of maternal origin, factors in
      the Baltic Sea during salmon feeding and migration, i.e., the chemical
      composition of food, may be decisive in the development of M74. The possible
      mechanisms by which oxidative stresses may develop in adult salmon are discussed
      in the review.

PMID- 17520931
TI  - Removal by sorption and in situ biodegradation of oil spills limits damage to
      marine biota: a laboratory simulation.
AB  - This study examined the efficiency of cotton grass fibers in removing diesel oil
      from the surface of water in conditions prevailing in the Baltic Sea. The effect
      of low temperature, salinity, and bacterial amendments were tested in laboratory
      scale set-ups, whereas 600-L mesocosms filled with Baltic Sea water were used for
      testing the effects of diesel oil and rapid removal of the oil on microorganisms,
      phytoplankton, and mussels. Cotton grass proved to be an excellent sorbent for
      diesel oil from the water surface at a low temperature. Inoculation with diesel
      enriched microorganisms enhanced degradation of oil significantly in laboratory
      scale experiments. In mesocosm experiments, the addition of diesel oil (0.66 mg
      L(-1), 0.533 L m(-2)) to the basins resulted in higher microbial density than in
      all other basins, including inoculated ones, suggesting that the Baltic Sea
      contains indigenous hydrocarbon degraders. The removal of oil with cotton grass
      significantly improved the survival of mussels in the mesocosm tests: 100%
      mortality in diesel basins versus 0% mortality in basins with cotton grass,
      respectively. However, the surviving mussels suffered from histopathological
      changes such as inflammatory responses, degenerations, and cell death. The
      observed rescuing effect was observable even when the cotton grass-bound oil was
      left in the water. The results underline the importance of rapid action in
      limiting damage caused by oil spills.

PMID- 17520933
TI  - Internal ecosystem feedbacks enhance nitrogen-fixing cyanobacteria blooms and
      complicate management in the Baltic Sea.
AB  - Eutrophication of the Baltic Sea has potentially increased the frequency and
      magnitude of cyanobacteria blooms. Eutrophication leads to increased
      sedimentation of organic material, increasing the extent of anoxic bottoms and
      subsequently increasing the internal phosphorus loading. In addition, the hypoxic
      water volume displays a negative relationship with the total dissolved inorganic
      nitrogen pool, suggesting greater overall nitrogen removal with increased
      hypoxia. Enhanced internal loading of phosphorus and the removal of dissolved
      inorganic nitrogen leads to lower nitrogen to phosphorus ratios, which are one of
      the main factors promoting nitrogenfixing cyanobacteria blooms. Because
      cyanobacteria blooms in the open waters of the Baltic Sea seem to be strongly
      regulated by internal processes, the effects of external nutrient reductions are
      scale-dependent. During longer time scales, reductions in external phosphorus
      load may reduce cyanobacteria blooms; however, on shorter time scales the
      internal phosphorus loading can counteract external phosphorus reductions. The
      coupled processes inducing internal loading, nitrogen removal, and the prevalence
      of nitrogen-fixing cyanobacteria can qualitatively be described as a potentially
      self-sustaining "vicious circle." To effectively reduce cyanobacteria blooms and
      overall signs of eutrophication, reductions in both nitrogen and phosphorus
      external loads appear essential.

PMID- 17520932
TI  - Bacterial diversity and function in the Baltic Sea with an emphasis on
      cyanobacteria.
AB  - In this article we summarize the current knowledge of Baltic Sea cyanobacteria,
      focusing on diversity, toxicity, and nitrogen fixation in the filamentous
      heterocystous taxa. We also review the recent results of our microbial diversity
      studies in planktonic and benthic habitats in the Baltic Sea. Based on molecular
      analyses, we have improved the understanding of cyanobacterial population
      structure by assessing genetic diversity within species that are morphologically
      inseparable. Moreover, we have studied microbial functions such as toxin
      production and nitrogen fixation in situ under different environmental
      conditions. Phosphorus limitation of bloom-forming, nitrogen-fixing cyanobacteria
      was clearly verified, emphasizing the importance of continuous efforts to reduce
      this element in the Baltic Sea. We have designed a rapid and reliable detection
      method for the toxic cyanobacterium Nodularia spumigena, which can be used to
      study bloom formation of this important toxin producer.

PMID- 17520934
TI  - Ecosystem consequences of cyanobacteria in the northern Baltic Sea.
AB  - Cyanobacteria of the Baltic Sea have multiple effects on organisms that influence
      the food chain dynamics on several trophic levels. Cyanobacteria contain several
      bioactive compounds, such as alkaloids, peptides, and lipopolysaccharides. A
      group of nonribosomally produced oligopeptides, namely microcystins and
      nodularin, are tumor promoters and cause oxidative stress in the affected cells.
      Zooplankton graze on cyanobacteria, and when ingested, the hepatotoxins
      (nodularin) decrease the egg production of, for example, copepods. However, the
      observed effects are very variable, because many crustaceans are tolerant to
      nodularin and because cyanobacteria may complement the diet of grazers in small
      amounts. Cyanobacterial toxins are transferred through the food web from one
      trophic level to another. The transfer rate is relatively low in the pelagic food
      web, but reduced feeding and growth rates of fish larvae have been observed. In
      the benthic food web, especially in blue mussels, nodularin concentrations are
      high, and benthic feeding juvenile flounders have been observed to disappear from
      bloom areas. In the littoral ecosystem, gammarids have shown increased mortality
      and weakening of reproductive success under cyanobacterial exposure. In contrast,
      mysid shrimps seem to be tolerant to cyanobacterial exposure. In fish larvae,
      detoxication of nodularin poses a metabolic cost that is reflected as decreased
      growth and condition, which may increase their susceptibility to predation.
      Cyanobacterial filaments and aggregates also interfere with both hydromechanical
      and visual feeding of planktivores. The feeding appendages of mysid shrimps may
      clog, and the filaments interfere with prey detection of pike larvae. On the
      other hand, a cyanobacterial bloom may provide a refuge for both zooplankton and
      small fish. As the decaying bloom also provides an ample source of organic carbon
      and nutrients for the organisms of the microbial loop, the zooplankton species
      capable of selective feeding may thrive in bloom conditions. Cyanobacteria also
      compete for nutrients with other primary producers and change the nitrogen (N):
      phosphorus (P) balance of their environment by their N-fixation. Further, the
      bioactive compounds of cyanobacteria directly influence other primary producers,
      favoring cyanobacteria, chlorophytes, dinoflagellates, and nanoflagellates and
      inhibiting cryptophytes. As the selective grazers also shift the grazing pressure
      on other species than cyanobacteria, changes in the structure and functioning of
      the Baltic Sea communities and ecosystems are likely to occur during the
      cyanobacterial bloom season.

PMID- 17520935
TI  - Macroalgal communities face the challenge of changing biotic interactions: review
      with focus on the Baltic Sea.
AB  - In diverse littoral communities, biotic interactions play an important role in
      community regulation. This article reviews how eutrophication modifies biotic
      interactions in littoral macroalgal communities. Eutrophication causes blooms of
      opportunistic algae, increases epibiotism, and affects regulation by grazers.
      Opportunistic algae and epibionts harm colonization and growth of perennial
      algae. Grazing regulates the density and species composition of macroalgal
      communities, especially at the early stage of algal colonization. Eutrophication
      supports higher grazer densities by increasing the availability and quality of
      algae to grazers. This may, on the one hand, enhance the capability of grazers to
      regulate and counteract the increase of harmful, bloom-forming macroalgae; on the
      other hand, it may increase grazing pressure on perennial species, with a poor
      tolerance of grazing. In highly eutrophic conditions, bloom-forming algae may
      also escape grazing control and accumulate. Increasing epibiotism and grazing
      threaten in particular the persistence of habitat-forming perennials such as the
      bladderwrack. An interesting property of biotic interactions is that they do not
      remain fixed but are able to evolve, as the traits of the interacting species
      adapt to each other and to abiotic conditions. The potential of plants and
      grazers to adapt is crucial to their chances to survive in changing environment.

PMID- 17520936
TI  - Changing environments or shifting paradigms? Strategic decision making toward
      water protection in Helsinki, 1850-2000.
AB  - The study examines the history of strategic decision-making concerning water
      protection in Helsinki, 1850-2000. We identified five major strategic decisions
      that occurred during the study period. The results indicate that strategic
      decision-making evolves in long-term policy cycles that last on average 20-30
      years. New policy cycles are caused by paradigm shifts. Paradigms are shared and
      predominant ways of understanding reality that help when groups must act to solve
      common and complex environmental problems. However the internal structure and
      external dynamics of paradigms are contradictory. Although paradigms serve
      initially as means to redefine problems and find creative solutions, as time goes
      by each paradigm seems to become also a barrier that restricts the introduction
      of new ways of thinking and acting. The power of paradigms lies in the fact that
      they can be defined as scientific but also social, political, or cultural
      agreements depending on the context.

PMID- 17520937
TI  - Legal requirements and wastewater discharges to Polish water bodies, 1945-2003.
AB  - The postwar development of water protection legislation and wastewater discharges
      is poorly known for the Baltic Sea region as a whole. This article presents
      national efforts to govern wastewater discharges in Poland using legal tools over
      the twentieth century with an emphasis on the postwar period, 1945-2003. The
      study also attempts to evaluate how the state authority responded to changing
      legal demands in terms of urban and industrial wastewater discharges in the
      postwar period. It outlines the main changes during the socialist regime in
      Poland and after it regained independence. Also the implications of Poland's
      integration into the European Union are briefly discussed. Mathematical
      calculations are used to illustrate some changes in legal requirements over time.

PMID- 17520938
TI  - Cold War and the environment: the role of Finland in international environmental
      politics in the Baltic Sea region.
AB  - The Convention on the Protection of the Marine Environment of the Baltic Sea Area
      signed in 1974 in Helsinki is probably the most important environmental agreement
      consummated in the Baltic Sea region. This article is the first study that
      explores the history of this agreement, also known as the Helsinki Convention, by
      using primary archival sources. The principal sources are the archives of the
      Ministry for Foreign Affairs of Finland. We examine the role of Finland in the
      process that led to the signing of the Helsinki Convention from the perspective
      of international politics. The study focuses primarily on Finnish, Swedish, and
      Soviet state-level parties from the end of the 1960s to 1974. We show that Cold
      War politics affected in several ways negotiations and contents of the Helsinki
      Convention. We also argue that the Soviet Union used the emerging international
      environmental issues as a new tool of power politics.

PMID- 17520939
TI  - Actors and arenas in hybrid networks: implications for environmental policymaking
      in the Baltic Sea region.
AB  - Policymaking within and among states is under pressure for change. One feature of
      this change is empirically observed as an activation of different network
      structures in the Baltic Sea Region, especially since the collapse of the Iron
      Curtain, the initiation of the Rio process, and the enlargement of the European
      Union. The contemporary theoretical debates about governance highlight the
      changing conditions for policymaking and implementation on all societal levels.
      This process of change, especially evident concerning environmental policies,
      includes new types of networks crossing state borders both at the supranational
      and the subnational levels. This article illuminates this process of change with
      empirical data from the project "Governing a Common Sea" (GOVCOM) within the
      Baltic Sea Research Program (BIREME).

PMID- 17520940
TI  - Management options and effects on a marine ecosystem: assessing the future of the
      Baltic.
AB  - We are using the coupled models in a decision support system, Nest, to evaluate
      the response of the marine ecosystem to changes in external loads through various
      management options. The models address all the seven major marine basins and the
      entire drainage basin of the Baltic Sea. A series of future scenarios have been
      developed, in close collaboration with the Helsinki Commission, to see the
      possible effects of improved wastewater treatment and manure handling, phosphorus
      free detergents, and less intensive land use and live stocks. Improved wastewater
      treatment and the use of phosphorus-free detergents in the entire region would
      drastically decrease phosphorus loads and improve the marine environment,
      particularly the occurrence of cyanobacterial blooms. However, the Baltic Sea
      will remain eutrophic, and to reduce other effects, a substantial reduction of
      nitrogen emissions must be implemented. This can only be obtained in these
      scenarios by drastically changing land use. In a final scenario, we have turned
      50% of all agricultural lands into grasslands, together with efficient wastewater
      treatments and a ban of phosphorus in detergents. This scenario will
      substantially reduce primary production and the extension of hypoxic bottoms,
      increase water transparency in the most eutrophied basins, and virtually
      eliminate extensive cyanobacterial blooms.

PMID- 17520941
TI  - Zoobenthos as indicators of ecological status in coastal brackish waters: a
      comparative study from the Baltic Sea.
AB  - A new method for classifying soft-bottom zoobenthic assemblages along the Finnish
      coasts (northern Baltic Sea) is presented and tested against traditional
      physicochemical monitoring data in the complex Archipelago Sea. Although
      multivariate methods for assessing the state of the marine environment have
      become widely used, few numerical indices can operate over a wide salinity range.
      We compare indices currently in use and propose a new index, BBI (brackish water
      benthic index), for the low-saline and species-poor Baltic coastal waters. BBI
      offers a salinity-corrected tool for classification of the soft-bottom zoobenthos
      under the demands of the European Union Water Framework Directive.

PMID- 17520942
TI  - Human dietary intake of organochlorines from Baltic herring: implications of
      individual fish variability and fisheries management.
AB  - This study examines the extent to which Finnish human dietary intake of
      organochlorines (PCDD/Fs and PCBs) originating from Northern Baltic herring can
      be influenced by fisheries management. This was investigated by estimation of
      human intake using versatile modeling tools (e.g., a herring population model and
      a bioenergetics model). We used a probabilistic approach to account for the
      variation in human intake of organochlorines originating from the variation among
      herring individuals. Our estimates were compared with present precautionary
      limits and recommendation for use. The results show that present consumption
      levels and frequencies of herring give a high probability of exceeding
      recommended intake limits of PCDD/Fs and PCBs. Furthermore, our results clearly
      demonstrate that in the risk management of dioxinlike organochlorines, regulating
      fishing (in this case increasing fishing pressure) is a far less effective way to
      decrease the risk than regulating the consumption of herring. Increased fishing
      would only slightly decrease organochlorine concentrations of herring in the
      Finnish fish market.

PMID- 17520943
TI  - Managing Baltic Sea fisheries under contrasting production and predation regimes:
      ecosystem model analyses.
AB  - Based on an earlier published ecosystem model, we have explored possible effects
      of different management scenarios for the Baltic Sea. The scenarios include an
      oligotrophication of the system, a drastic increase in the number of seals, and
      changes in the fishery management. From these simulations we conclude that
      fisheries, seals, and eutrophication all have strong and interacting impacts on
      the ecosystem. These interactions call for integrated management. The modeling
      highlights the potential for conflicts among management mandates such as
      flourishing fisheries, rebuilt seal populations, and substantially reduced
      eutrophication. The results also suggest that fisheries management reference
      points have to be adjusted in response to changes in the presence of natural
      predators or ecosystem productivity.

PMID- 17520944
TI  - Searching efficient protection strategies for the eutrophied Gulf of Finland: the
      combined use of 1D and 3D modeling in assessing long-term state scenarios with
      high spatial resolution.
AB  - An experiment combining the use of two ecosystem models was conducted to search
      for effective protection strategies for the Gulf of Finland (Baltic Sea).
      Reference and scenario simulations were first run with a one-dimensional (1D)
      model for seven main basins of the entire Baltic Sea until steady state was
      achieved. The obtained basinwise distributions of inorganic nitrogen (N) and
      phosphorus (P), as well as sediment labile P, were then used to initiate 5-y
      simulations with a three-dimensional (3D) ecosystem model. The results suggest
      that relatively small local load reductions (the "Finland" scenario) would
      improve only the state of adjacent coastal waters significantly. This would be
      the case, even for runs covering several decades, which clearly exceed the
      residence times of nutrients in the Gulf of Finland. A significant decrease from
      a substantial loading source to the Gulf (the "St. Petersburg" scenario) would
      decrease cyanobacterial biomasses in the entire Gulf of Finland and also
      immediately outside it. A reduction in the current Polish nutrient loads would
      improve the situation in the whole Baltic Proper and cause an extensive decline
      in cyanobacterial biomasses in the Gulf of Finland, as well. However, it would
      take several decades until the improvement caused by reducing loads in the
      "Poland" scenario is seen, while in the "St. Petersburg" scenario the
      corresponding time lag would only be a few years. Our results suggest that the
      common water protection policy in the Baltic Sea region should have the largest
      nutrient sources as its primary target, regardless of their location and country.

PMID- 17520945
TI  - Improvement of Baltic proper water quality using large-scale ecological
      engineering.
AB  - Eutrophication of the Baltic proper has led to impaired water quality,
      demonstrated by, e.g., extensive blooming of cyanobacteria during the premium
      summer holiday season and severe oxygen deficit in the deepwater. Sustainable
      improvements in water quality by the reduction of phosphorus (P) supplies will
      take several decades before giving full effects because of large P storages both
      in soils in the watershed and in the water column and bottom sediments of the
      Baltic proper. In this article it is shown that drastically improved water
      quality may be obtained within a few years using large-scale ecological
      engineering methods. Natural variations in the Baltic proper during the last
      decades have demonstrated how rapid improvements may be achieved. The present
      article describes the basic dynamics of P, organic matter, and oxygen in the
      Baltic proper. It also briefly discusses the advantages and disadvantages of
      different classes of methods of ecological engineering aimed at restoring the
      Baltic proper from eutrophication effects. Preliminary computations show that the
      P content might be halved within a few years if about 100 kg O2 s(-1) are
      supplied to the upper deepwater. This would require 100 pump stations, each
      transporting about 100 m3 s(-1) of oxygen-rich so-called winter water from about
      50 to 125 m depth where the water is released as a buoyant jet. Each pump station
      needs a power supply of 0.6 MW. Offshore wind power technology seems mature
      enough to provide the power needed by the pump stations. The cost to install 100
      wind-powered pump stations, each with 0.6 MW power, at about 125-m depth is about
      200 million Euros.

PMID- 17520946
TI  - Conflicts of interest.

PMID- 17520947
TI  - A mechanical evaluation of implants placed with different surgical techniques
      into the trabecular bone of goats.
AB  - The aim of the study was to assess the effects of surgical technique and implant
      surface roughness on implant fixation. A total of 48 screw implants with machined
      or etched surface topographies were placed into the femoral condyles of goats.
      The implant sites were prepared by a conventional technique, by undersized
      preparation, or by the osteotome technique. Bone tissue responses were evaluated
      after 12 weeks of healing by removal torque testing and histologic analysis using
      scanning electron microscope. The cumulative removal torque value of the etched
      implants placed with the undersized technique (98 +/- 29 Ncm) was higher (50 +/-
      35 Ncm) to a level of statistical significance than machined surface implants
      placed by the osteotome technique. Scanning electron microscope evaluation
      indicated that all implants showed interfacial bone contact. The torque test
      resulted in fracture at the bone-implant interface for all experimental
      conditions. Installation of etched implants using an undersized preparation of
      the implant bed resulted in superior bonding strength with the surrounding bone
      at 12 weeks after surgery. Evidently, the undersized preparation technique
      improved the early fixation of oral implants in this study.

PMID- 17520948
TI  - Cylindrical dental implants with hydroxyapatite- and titanium plasma spray-coated
      surfaces: 5-year results.
AB  - Clinical follow-up was conducted on 127 cylindrical implants placed in 21
      patients after 5 years of function: 75 implants were coated with titanium plasma
      spray (TPS) and 52 implants were coated with hydroxyapatite (HA). The aim of the
      study was to assess possible differences in clinical function and success rates
      for each implant type. Clinical and radiographic evaluations were conducted, and
      the periodontal indices of gingival bleeding, plaque, and calculus were measured.
      Cumulative data were analyzed for differences by implant type and jaw location.
      No significant differences were found between the 2 implant systems according to
      the periodontal parameters studied; however, 5-year success rates were 86.7% for
      TPS-coated implants and 94.3% for HA-coated implants. The periodontal probe index
      presented abnormal values in the patients with systemic disease and those who
      were provisionally restored with single-tooth restorations, complete screw
      retained dentures, and fixed partial dentures. There were no differences
      regarding implant placement when mandibles and maxillae were compared. Long-term
      success rates were outstanding for HA-coated implants and acceptable for TPS
      coated implants after 5 years of function. No significant differences were found
      between the 2 surfaces.

PMID- 17520949
TI  - Electronic percussive testing of the stability of an immediately provisionalized
      implant placed into a fresh extraction socket: a pilot evaluation.
AB  - It is important to achieve primary stabilization of dental implants that will be
      immediately loaded. Noninvasive devices that test the stability of immediately
      provisionalized implants placed into fresh extraction sockets are discussed. A
      titanium threaded implant was placed into a fresh extraction socket of a
      patient's nonrestorable mandibular right canine. The implant received an interim
      restoration immediately following its placement. The stability of the bone
      implant complex was evaluated from the day of implant insertion through day 246
      using an electronic percussive testing instrument. During the first month the
      bone-implant complex became progressively less stable reaching a peak measured
      level of instability at 30 days postimplantation. This was followed by
      progressive stabilization first measured on day 46 as the implant continued to
      osseointegrate. These findings suggest that the bone-implant complex became less
      stable during the first month after implant placement and was followed by a
      period of progressive stabilization reflecting bone maturation around the
      implant. A search of the literature found similar results in a study of single
      stage implants (not immediately provisionalized) using resonance frequency
      analysis. The known sequence of wound healing around dental implants is reviewed
      to explain the findings of this pilot evaluation. Studies that use noninvasive
      testing devices to assess implant stability at placement and during healing may
      provide information that can help to optimize implant treatment outcomes.

PMID- 17520950
TI  - Flapless dental implant placement.
AB  - Flapless dental implant placement is possible in selected patients but limited to
      those sites with adequate or augmentable attached gingiva and available bone
      volume and density. Inadequate attached gingiva, available bone, and bone density
      may be augmented by pre-, intra-, or postoperative procedures. Bone ridge contour
      can be approximated by using a described fast set polyvinyl siloxane site
      evaluation technique. Assuming adequate length and height, a bone width of 5 mm
      is usually acceptable for standard diameter implants (3.5-4.2 mm). However,
      implant placement in sites with parabolic shaped ridges may need to be placed
      deeper to avoid vertical bone loss and implant thread exposure. Inadequate bone
      volume, less than 5 mm of bone width, may be developed by ridge expansion (split
      ridge) techniques. With ridge expansion, complications may arise such as
      malposition and labyrinthine concussion. Malposition may be corrected
      intraoperatively or grafted for a later implant placement. Labyrinthine
      concussion is usually of short duration but may be treated with head maneuvers.
      Sites with 2 mm or less width of available bone may not be treated flaplessly and
      may be more appropriately treated with extracortical augmentation grafting.

PMID- 17520951
TI  - Effect of anesthetics containing lidocaine and epinephrine on cardiovascular
      changes during dental implant surgery.
AB  - The purpose of this study was to evaluate cardiovascular changes during dental
      implant surgery using 2% lidocaine with 1:80 000 epinephrine. Eleven normotensive
      subjects, ranging from 18 to 56 years, were selected to undergo dental implant
      surgery in the jaw. They were monitored in the pre-, intra-, and postsurgical
      periods by continuous noninvasive automatic arterial pressure and cardiac
      frequency measurements taken every 2 minutes. Parameter scores were obtained for
      the following phases: P1, 15 minutes during preparation of the patient (control
      period); P2, before anesthesia; P3, immediately after anesthesia; P4, 2 minutes
      into anesthesia; P5, during incision and detachment; P6, during perforation; P7,
      during implant placement; P8, during suturing; P9, on completion; and P10, 10
      minutes after termination. Individualized statistical analysis for each group
      during the pre-, intra-, and postoperative periods were performed by analysis of
      variance. The greatest variations in systolic pressure were increases of 2.29%
      during phase P2 and 2.59% in phase P5. Diastolic pressure decreased during phase
      P6 (-2.58%) and increased in P10 (3.27%). The greatest changes in heart rate
      occurred in phase P10 (-3.24%). There were no statistically significant changes
      among the evaluated phases (P > .05). In conclusion, there were no changes in the
      analyzed cardiocirculatory parameters during dental implant surgery (systolic,
      diastolic, and mean arterial blood pressures and heart rate) in normotensive
      subjects anesthetized with 2% lidocaine with epinephrine 1:80000.

PMID- 17520953
TI  - A misdirected step in the right direction.

PMID- 17520952
TI  - Histologic evaluation of a provisional implant retrieved from man 7 months after
      placement in a sinus augmented with calcium sulphate: a case report.
AB  - Little is known about the in vivo healing processes at the interface of implants
      placed in different grafting materials. For optimal sinus augmentation, a bone
      graft substitute that can regenerate high-quality bone and enable the
      osseointegration of load-bearing titanium implants is needed in clinical
      practice. Calcium sulphate (CaS) is one of the oldest biomaterials used in
      medicine, but few studies have addressed its use as a sinus augmentation material
      in conjunction with simultaneous implant placement. The aim of the present study
      was to histologically evaluate an immediately loaded provisional implant
      retrieved 7 months after simultaneous placement in a human sinus grafted with
      CaS. During retrieval bone detached partially from one of the implants which
      precluded its use for histologic analysis. The second implant was completely
      surrounded by native and newly formed bone, and it underwent histologic
      evaluation. Lamellar bone, with small osteocyte lacunae, was present and in
      contact with the implant surface. No gaps, epithelial cells, or connective
      tissues were present at the bone-implant interface. No residual CaS was present.
      Bone-implant contact percentage was 55% +/- 8%. Of this percentage, 40% was
      represented by native bone and 15% by newly formed bone. CaS showed complete
      resorption and new bone formation in the maxillary sinus; this bone was found to
      be in close contact with the implant surface after immediate loading.

PMID- 17520954
TI  - The scales of justice: do they need rebalancing? A non-politician looks at the
      criminal justice system.

PMID- 17520955
TI  - Variation in proportion indices and angles between selected facial landmarks with
      rotation in the Frankfort plane.
AB  - A number of different techniques are employed in facial image comparison of
      living persons. In this study, the effect of rotation on angles and proportion
      indices between selected facial landmarks is evaluated as a first step to assess
      whether facial anthropometry could be usefully applied to facial image
      comparison. The faces of five volunteers were photographed in the Frankfort plane
      at different angles of rotation from 0 degree (frontal) to 90 degrees (side
      view), rotating every 10 degrees both clockwise and counter-clockwise. Four
      landmarks were used: right and left ectocanthions, nasion, and stomion. The
      proportion indices of the measurements between these landmarks were calculated as
      well as the angles created by the lines connecting the same landmarks. The
      results show a consistent and predictable variation between the five subjects.
      With rotation, the greatest variation is seen where horizontal landmark
      connecting lines are combined with the ectocanthion/ stomion lines or
      nasion/stomion. There is less variation in the proportion indices for vertical
      and diagonally orientated landmark connecting lines.

PMID- 17520956
TI  - Diversity and forensics: diversity in hiring is not enough.
AB  - The current organization of forensic work may induce biases in forensic analysis
      (Risinger et al., 2002). Such biases may have a differential impact across
      groups, creating differential bias. We should reorganize forensic work to reduce
      this bias. The obvious strategy of hiring ethnically diverse forensic workers
      will not work. 'Us vs. Them' thinking is an important source of differential
      bias. The definitions of 'Us' and 'Them' are socially conditioned. The current
      organization of forensic work induces forensic workers to see the police as 'Us'
      and suspects of any ethnicity as 'Them'. Thus, differential biases in arrests
      become differential biases in forensic analysis. I argue that my prior proposal
      for 'competitive self regulation' (Koppl, 2005) would reduce or eliminate
      differential bias. Competitive self regulation divides forensic work among
      several, unrelated parties, and hides extraneous, bias-inducing information from
      forensic analysts. These measures separate forensic workers from the police,
      reduce their sense of identification with the police, and hide from them the
      knowledge of what result the police are looking for. My argument builds on a
      literature on biases, Us vs. Them thinking, and the role of 'coalitional
      alliances' (Kurzban et al., 2001) in bias formation.

PMID- 17520957
TI  - Sudden unexpected death associated with lymphocytic thyroiditis.
AB  - A forensic autopsy study comprising 125 cases was carried out retrospectively in
      order to evaluate pathological changes in the thyroid gland in different groups
      of death. The five groups selected consecutively were: (i) opiate addicts who
      died from an overdose, (ii) alcoholics who died as a result of their alcohol
      abuse, (iii) cases of fatal poisoning other than opiate addicts, (iv) unknown
      cause of death and (v) controls without prior disease. Tissue samples from the
      thyroid gland were cut and stained with haematoxylin and eosin and van Gieson.
      Histology examinations were subsequently performed blind with semiquantitative
      assessment of the following six parameters: (a) height of the follicular
      epithelium, (b) the amount of lymphocytes, (c) the presence of plasma cells, (d)
      hyperplastic follicular changes, (e) oxyphilic changes, and (f) fibrosis. The
      most striking result was the finding of extensive lymphocytic infiltration of the
      thyroid parenchyma in five of the 124 cases, of which four belonged in the group
      of 'unknown cause of death'. This discovery leads to reflections regarding
      lymphocytic thyroiditis as a cause of death, either by itself or in combination
      with other disorders. Silent (painless) thyroiditis, especially, is easily
      overlooked at autopsy as there are no macroscopic changes and often no prior
      symptoms or history of thyroid disease pointing towards this condition. Analyses
      of thyroid hormones are unreliable in predicting endocrine status in life.
      Routine microscopy of the thyroid gland is therefore advocated in cases of sudden
      unexpected death in order to diagnose thyroid disease, in particular silent
      (painless) thyroiditis.

PMID- 17520958
TI  - The use of proteomics to study wound healing: a preliminary study for forensic
      estimation of wound age.
AB  - Proteomics is the analysis of the protein complement of the genome. The technique
      involves extracting proteins from the tissue being examined; separating the
      proteins using methods such as two-dimensional gel electrophoresis and then
      identifying the proteins by mass spectrometry. This paper describes the
      application of proteomics to incised wounds of the rat to determine if this
      technology could be applied to the important forensic issue of determining the
      age of wounds. Experimental incised skin wounds were inflicted on rats 5, 15, 30
      and 60 minutes, 3, 6, 12 and 24 hours and 2, 5, 7 and 12 days before euthanasia.
      Each wound was excised and frozen at 80 degrees C; protein extracts were prepared
      and subjected to two-dimensional polyacrylamide gel electrophoresis over the
      range pH 3 to pH 10. Protein spots were identified using Matrix-assisted Laser
      Desorption/Ionisation Time-of-Flight (MALDI-TOF) mass spectrometry. A number of
      proteins were identified in skin wounds. After wounding the most prominent change
      was in the level of haemoglobin, which was elevated in wounds five minutes old
      and remained elevated for three hours, falling to near control levels after 12
      hours. This pilot study has illustrated the feasibility for proteomics to be
      applied to determining wound age.

PMID- 17520959
TI  - The effect of aluminium phosphide on the human brain: a histological study.
AB  - The study was conducted on 317 cases of poisoning in the Varanasi region, India,
      between January 2002 and August 2003. Aluminium phosphide (Celphos) was used by
      239 victims (75.40% of the total) and was used in 69.03% of male and 30.96% of
      female cases. It was commoner in males from both rural and urban areas and in the
      21-30 year age group. Microscopic investigation of the cerebral and cerebellar
      cortex showed distinct changes due to the effect of celphos. Findings in the
      cerebral cortex revealed disorganisation of the different layers, round shaped
      neurons with a convex border, degenerated Nissl granules in the cytoplasm and a
      deeply stained degenerated eccentric nucleus. Findings in the cerebellar cortex
      included degenerated neurons, the infiltration of round cells into the molecular
      layer and the disappearance of the processes of Purkinje cells. Degenerate nuclei
      were surrounded by scavenger cells in the granular layer. The subcortical zone of
      the brain revealed a paucity of glial cells, degeneration of nerve fibres and the
      appearance of necrotic patches.

PMID- 17520960
TI  - Sudden natural deaths in Edirne, Turkey, from 1984 to 2005.
AB  - The aim of this study is to evaluate the characteristics of sudden natural deaths
      (SND) in forensic autopsy cases which were performed in Trakya University
      Department of Forensic Medicine, Edirne, Turkey. For each case, a complete
      autopsy, toxicological screening and histological examination were performed.
      Deaths due to unnatural causes, alcohol, drug overdose and undetermined causes
      (negative autopsy) were excluded from the study. Autopsy reports of 959
      consecutive forensic cases performed in a 22-year period were reviewed. Two
      hundred and seventy-eight (278) SNDs were identified, involving 232 males (83.4%)
      and 46 females (16.6%). The age group of 50-59 years accounted for 21.58% of the
      cases. In the majority (55%) the cause of death was related to the cardiovascular
      system--principally ischemic heart disease. The second most common cause of SND
      was related to the respiratory system (19.1%), especially pneumonia. Most of the
      SNDs occurred in the winter months. Ethyl alcohol was detected in 5.3% of cases.
      In conclusion, sudden natural deaths related to the cardiovascular system are
      shown to be a significant problem in the Trakya region of Turkey.

PMID- 17520961
TI  - Death due to traumatic railway injury.
AB  - This study was carried out on 88 railway related deaths in order to determine the
      specific pattern and distribution of wounds. Of the 88 victims, 79.5% were males
      and 20.5% were females. The majority were in the age group of 21-40 years. Most
      of the victims died as the result of an accident (80.7%). Of the 17 suicide
      cases, ten deaths occurred during the night. In 71 railway accident deaths, 64.8%
      of victims were pedestrians; thirty-five victims were illiterate and two had
      consumed alcohol. Decapitation wounds were more common in suicidal deaths and the
      head was the body region most commonly involved in railway accidents. Our results
      indicate that railway related deaths could be prevented by surveillance,
      education and public awareness.

PMID- 17520962
TI  - Lightning fatalities in the Transkei sub-region of South Africa.
AB  - Lightning is a particularly unsettling product of bad weather. It kills more
      people than other natural disasters such as floods, hurricanes, and tornadoes,
      but, because lightning usually kills people one at a time, it tends to be an
      underrated hazard. High risk groups are uneducated, unsheltered and rural people.
      This study was carried out to determine the incidence of lightning fatalities in
      the Transkei sub-region. It is a review of records between 1993 and 2004 from the
      medico-legal autopsies at Umtata General Hospital (UGH). During the study period
      there were 10,860 autopsies performed on those who died of trauma and other
      unnatural circumstances which included 151 (1.4%) lightning fatalities. This
      represents 0.31 deaths per million per year. The highest (0.5/million) was in
      1999, and the lowest (0.13/million) in 1997. The age of the victims ranged from 1
      to 82 years, with a mean of 22 years. Males and females were almost equally
      represented (50%). The highest number of deaths (26.5%) was in the age group of
      11 to 20 years, and the lowest number (2.7%) in the age group of 70+ years. There
      is a high incidence of lightning fatalities in the Transkei sub-region of South
      Africa. People need to be educated to disregard the myths of lightning strike.

PMID- 17520963
TI  - Asphyxia in a confined space: a case report.
AB  - We describe a death in a hospital wardrobe of a 40-year-old male suffering from
      HIV infection and lobar pneumonia. On the basis of circumstantial evidence and
      autopsy findings we conclude that the cause of death was asphyxia in a confined
      space as a result of several pathomechanical factors. As well as establishing the
      cause and manner of death, the interpretation of the case involves the evaluation
      of the professional responsibility of the medical personnel. This report
      discusses different aspects concerning the cause, mechanism, and manner of death
      and illustrates various problems encountered in forensic pathology.

PMID- 17520964
TI  - Filigree burn of lightning: two case reports.
AB  - Lightning is a powerful natural electrostatic discharge produced during a
      thunderstorm. The electric current passing through the discharge channels is
      direct with a potential of 1000 million volts or more. Lightning can kill or
      injure a person by a direct strike, a side-flash, or conduction through another
      object. Lightning can cause a variety of injuries in the skin and the
      cardiovascular, neurological and ophthalmic systems. Filigree burn of lightning
      is a superficial burn and very rare. Two cases of death from lightning which have
      this rare finding are reported and discussed.

PMID- 17520965
TI  - Ethical problems in the investigation of autoerotic deaths: three case reports.
AB  - Despite a large body of literature on autoerotic deaths, there are very few
      articles focusing on the ethical aspect of such deaths. Furthermore, as far as we
      know, there is no paper that has studied the forensic teams' reactions to those
      deaths. We present three cases of autoerotic death involving ethical problems in
      the case's management. Despite the usual high professionalism and respectful
      behaviour of the forensic staff, we observed in these cases breaches of
      confidentiality, laxity of work and an offhand attitude. Ethical dimensions are
      discussed.

PMID- 17520966
TI  - Masking and bondage in suicidal hanging: a case report.
AB  - The body of a 35-year-old man was found hanging in a relatively isolated place
      outdoors. A vest was wrapped over his head, neck and lower part of the face. The
      hands were loosely tied in front of the body. The vest was tucked between the
      neck and the ligature, to act as a pad. Thorough scene examination and post
      mortem examination excluded any evidence of foul play. Although bondage is
      usually associated with autoerotic practices in asphyxiation deaths, it was
      established that this case was a suicide. DNA was used as a supportive measure to
      determine that the handkerchief and vest belonged to the deceased.

PMID- 17520967
TI  - Strangles vaccines in trouble again.

PMID- 17520968
TI  - The effect of induced forelimb lameness on thoracolumbar kinematics during
      treadmill locomotion.
AB  - REASONS FOR PERFORMING STUDY: Lameness has often been suggested to result in
      altered movement of the back, but there are no detailed studies describing such a
      relationship in quantitative terms. OBJECTIVES: To quantify the effect of induced
      subtle forelimb lameness on thoracolumbar kinematics in the horse. METHODS:
      Kinematics of 6 riding horses was measured at walk and at trot on a treadmill
      before and after the induction of reversible forelimb lameness grade 2 (AAEP
      scale 1-5). Ground reaction forces (GRF) for individual limbs were calculated
      from kinematics. RESULTS: The horses significantly unloaded the painful limb by
      11.5% at trot, while unloading at walk was not significant. The overall flexion
      extension range of back motion decreased on average by 0.2 degrees at walk and
      increased by 3.3 degrees at trot (P<0.05). Changes in angular motion patterns of
      vertebral joints were noted only at trot, with an increase in flexion of 0.9
      degrees at T10 (i.e. angle between T6, T10 and T13) during the stance phase of
      the sound diagonal and an increase in extension of the thoracolumbar area during
      stance of the lame diagonal (0.7degrees at T13, 0.8 degres at T17, 0.5 degres at
      L1, 0.4 degrees at L3 and 0.3 degrees at L5) (P<0.05). Lameness further caused a
      lateral bending of the cranial thoracic vertebral column towards the lame side
      (1.3 degrees at T10 and 0.9 degrees at T13) (P<0.05) during stance of the lame
      diagonal. CONCLUSIONS: Both range of motion and vertebral angular motion patterns
      are affected by subtle forelimb lameness. At walk, the effect is minimal, at trot
      the horses increased the vertebral range of motion and changed the pattern of
      thoracolumbar motion in the sagittal and horizontal planes, presumably in an
      attempt to move the centre of gravity away from the lame side and reduce the
      force on the affected limb. POTENTIAL RELEVANCE: Subtle forelimb lameness affects
      thoracolumbar kinematics. Future studies should aim at elucidating whether the
      altered movement patterns lead to back and/or neck dysfunction in the case of
      chronic lameness.

PMID- 17520970
TI  - Electrosurgery as the sole means of haemostasis during the laparoscopic removal
      of pathologically enlarged ovaries in mares: a report of 55 cases.
AB  - REASONS FOR PERFORMING STUDY: There is little published clinical evidence on the
      use of a laparoscopic approach for the removal of pathologically enlarged ovaries
      in standing mares. OBJECTIVES: To show the orders of success and complication
      rates that can be expected if pathologically enlarged ovaries are removed from
      standing, sedated mares under laparoscopic guidance using only electrosurgical
      means of haemostasis. METHODS: A retrospective analysis was made of 55 mares in
      which the removal of an enlarged ovary was attempted by applying a standard
      laparoscopic procedure for routine ovariectomy in standing mares including a
      reliance solely on one of 2 types of electrosurgical bipolar forceps with an
      integrated guillotine for haemostasis and transection of the ovarian pedicle. The
      outcomes and complications encountered were recorded. Logistic regression
      analysis was performed to identify the risk of any complications associated with
      the size of the ovary removed and the instrument used. RESULTS: In 54 of the 55
      mares, the surgery was successfully accomplished by the planned approach. In one
      mare there was significant intraoperative haemorrhage and this necessitated the
      additional use of a prosthetic haemostatic device. The only other complications
      encountered were post operative abdominal discomfort (n = 9), delayed incisional
      wound healing (n = 6) and iatrogenic uterine puncture (n = 2). One mare developed
      a rectal tear, but not as a direct complication of the surgical procedure. None
      of these prevented a long-term successful outcome. CONCLUSIONS: The removal of
      pathologically enlarged ovaries (up to 30 cm diameter) from mares under standing
      sedation can be accomplished predictably and safely by applying the standard
      laparoscopic approach that is established for routine laparoscopic ovariectomy,
      including a reliance solely on endoscopic electrosurgery instruments for
      haemostasis of the ovarian pedicle. POTENTIAL RELEVANCE: This study shows that
      the simple standing laparoscopic technique now favoured for routine ovariectomy
      can be used safely and reliably for the removal of pathologically enlarged
      ovaries. This promises to be of significant clinical advantage to mares so
      affected.

PMID- 17520969
TI  - Equine herpesvirus-1-specific interferon gamma (IFNgamma) synthesis by peripheral
      blood mononuclear cells in thoroughbred horses.
AB  - REASONS FOR PERFORMING STUDY: An assay has been developed that measures EHV-1
      specific interferon gamma synthesis (IFNgamma), a cytokine produced following the
      activation of memory T lymphocytes and therefore a measure of cell mediated
      immunity. The method requires validation in the field. OBJECTIVES: To measure the
      frequency of EHV-1 specific, IFNgamma synthesising peripheral blood mononuclear
      cells (PBMC) in a population of Thoroughbred horses, and examine its relationship
      with age, gender, premises and history of vaccination or field infection with EHV
      1. METHODS: Lymphocytes from 200 Thoroughbred horses were stimulated with EHV-1
      in vitro, and IFNgamma detected using a monoclonal antibody and indirect
      immunofluorescence. Percent positive cells were enumerated by flow cytometric
      analysis and the results described and compared statistically between groups.
      RESULTS: The frequency of IFNgamma+ PBMC was significantly higher in animals age
      >5 years compared with 2-4 years, in females vs. males, on stud farms vs.
      training yards and following vaccination of 2-year-olds with inactivated virus
      compared with nonvaccinates. Age strongly confounded all these associations and
      care must therefore be taken interpreting these results. Mares exposed to a field
      infection with EHV-1 also had higher frequencies of IFNgamma+ PBMC than other
      vaccinated horses. CONCLUSIONS: The frequency of EHV-1 specific, IFNgama+ PBMC
      among the sample Thoroughbred population was diverse but lowest in young,
      unvaccinated horses-in-training. POTENTIAL RELEVANCE: The frequency of EHV-1
      specific lymphocytes synthesising IFNgamma in this population may be associated
      with its susceptibility to infection with this virus. This easy technique may be
      applied to monitor the antigenicity of vaccines and their effectiveness at
      stimulating cellular immunity.

PMID- 17520971
TI  - Trimetoquinol: bronchodilator effects in horses with heaves following aerosolised
      and oral administration.
AB  - REASON FOR PERFORMING STUDY: The bronchodilator effects of trimetoquinol (TMQ)
      have been studied when administered i.v. or intratracheally, but not in an
      aerosolised form. OBJECTIVES: To define the relationship between the therapeutic
      and adverse responses (therapeutic index) of TMQ when administered as an aerosol
      or by the oral route. METHODS: Increasing doses of TMQ were administered to
      horses with heaves as an aerosol and by the oral route. Dose ranged 100-1000
      microg/horse for aerosolised TMQ and from 6-60 microg/kg bwt for the oral route.
      Airway and cardiac effects were assessed by measurement of maximal change in
      pleural pressure (deltaPplmax) and heart rate (HR), respectively. Side effects of
      sweating, agitation and muscle trembling were scored subjectively. Duration of
      action of aerosolised (1000 pg/horse) and oral (6-60 microg/kg bwt) TMQ was
      evaluated over 6 h. RESULTS: Aerosol administration of TMQ caused dose-dependent
      bronchodilation but did not change HR or cause other observable side effects.
      When 1000 microg/horse was administered via aerosol, TMQ produced a 2-phase
      bronchodilation; an immediate effect lasting up to 30 min and a second phase
      between 2 and 4 h. Oral TMQ was therapeutically ineffective. CONCLUSION: Aerosol
      administration of TMQ is a safe and effective method of producing bronchodilation
      in horses.

PMID- 17520972
TI  - Histological evaluation of the equine larynx after unilateral laser-assisted
      ventriculocordectomy.
AB  - REASONS FOR PERFORMING STUDY: Trans-endoscopic laser surgery, such as unilateral
      laser-assisted ventriculocordectomy (LVC), has gained popularity in the treatment
      of RLN because a laryngotomy incision or general anaesthesia are not required.
      However, removal of the vocal fold and ventricle takes considerable laser energy
      and could cause collateral tissue damage, including injury to the adjacent
      laryngeal cartilages. OBJECTIVES: To document the histological effects of laser
      surgery on laryngeal tissues in horses that have undergone LVC for the treatment
      of laryngeal hemiplegia (LH). METHODS: Six horses were used: 4 with
      experimentally induced LH that had subsequently undergone LVC 6 months prior to
      euthanasia; and, 2 horses were used as controls. One of the control horses with
      naturally occurring LH was used to study the effect of neuropathy alone, whereas
      the other was subjected to euthanasia immediately following LVC to evaluate the
      acute effect of laser surgery. Using a band saw, each larynx was sectioned
      transversely at 5 mm intervals and evaluated histologically. RESULTS: Acutely,
      LVC caused thermal damage to adjacent soft tissues but did not affect the
      histology of the laryngeal cartilages. Six months after LVC, laryngeal cartilages
      were histologically normal and there was squamous metaplasia of the repaired
      laryngeal mucosa, resulting in restitution of the mucosal integrity. CONCLUSIONS:
      Using a diode laser in contact fashion at 20 W, LVC can be used to remove the
      laryngeal vocal fold and ventricle without causing laryngeal cartilage damage.
      POTENTIAL RELEVANCE: Laryngeal chondritis is an unlikely consequence of LVC.

PMID- 17520973
TI  - Effect of extracorporeal shock wave therapy on the biochemical composition and
      metabolic activity of tenocytes in normal tendinous structures in ponies.
AB  - REASONS FOR PERFORMING STUDY: Extracorporeal shockwave therapy (ESWT) has
      recently been introduced as a new therapy for tendon injuries in horses, but
      little is known about the basic mechanism of action of this therapy. OBJECTIVES:
      To study the effect of ESWT on biochemical parameters and tenocyte metabolism of
      normal tendinous structures in ponies. METHODS: Six Shetland ponies, free of
      lameness and with ultrasonographically normal flexor and extensor tendons and
      suspensory ligaments (SL), were used. ESWT was applied at the origin of the
      suspensory ligament and the mid-metacarpal region of the superficial digital
      flexor tendon (SDFT) 6 weeks prior to sample taking, and at the mid-metacarpal
      region (ET) and the insertion on the extensor process of the distal phalanx (EP)
      of the common digital extensor tendon 3 h prior to tendon sampling. In all
      animals one front leg was treated and the other front leg was used as control.
      After euthanasia, tendon explants were harvested aseptically for in vitro cell
      culture experiments and additional samples were taken for biochemical analyses.
      RESULTS: In the explants harvested 3 h after treatment, glycosaminoglycan (GAG)
      and protein syntheses were increased (P<0.05). The synthesis of all measured
      parameters was decreased 6 weeks after ESWT treatment. Biochemically, the level
      of degraded collagen was increased 3 h after treatment (P<0.05). Six weeks after
      treatment, there was a decrease of degraded collagen and GAG contents. DNA
      content had not changed in either tendon samples or explants after culturing.
      CONCLUSIONS: ESWT causes a transient stimulation of metabolism in tendinous
      structures of ponies shortly after treatment. After 6 weeks metabolism has
      decreased significantly and GAG levels are lower than in untreated control limbs.
      POTENTIAL RELEVANCE: The stimulating short-term effect of ESWT might accelerate
      the initiation of the healing process in injured tendons. The long-term effect
      seems less beneficial. Further research should aim at determining the duration of
      this effect and at assessing its relevance for end-stage tendon quality.

PMID- 17520974
TI  - Seroprevalence of antibotulinum neurotoxin type C antibodies in horses in Israel.
AB  - REASONS FOR PERFORMING STUDY: Clostridium botulinum type C is prevalent in Israel
      and outbreaks recorded in many species, other than horses. Association between
      levels of anti-BoNT/C antibodies and equine grass sickness (EGS) have been
      demonstrated but seroprevalence of anti-BoNT/C antibodies in horses has not been
      reported nor has EGS been reported in Israel. OBJECTIVES: To determine the
      seroprevalence of specific anti-BoNT/C antibodies in horses in Israel and to
      determine whether age, breed and gender, or geographical region of farms are
      potential risk factors for exposure to BoNT/C. HYPOTHESIS: Anti-BoNT/C antibodies
      are prevalent among horses in Israel and farm and horse-level variables are
      associated with increased risk for exposure. METHODS: Serum samples from 198
      horses were collected and the levels of specific anti-BoNT/C antibodies were
      determined using enzyme-linked immunosorbent assay (ELISA). For each categorical
      variable indicator variables were created and the odds ratio (OR) and 95%
      confidence intervals (95% CI) for the outcome variable were calculated using a
      univariable and multivariable logistic regression models. RESULTS: A total of 61
      (30.8%) horses were ELISA positive for anti-BoNT/C IgG antibodies. The farm and
      its geographical region were associated significantly with seropositivity, horse
      level variables, such as gender and breed, were also associated with
      seropositivity. Quarter Horse and Warmblood mares placed in the southern region
      of Israel had the highest odds to be tested positive for anti-BoNT/C IgG
      antibodies. CONCLUSIONS AND POTENTIAL RELEVANCE: Several farm and various horse
      level risk factors for exposure to BoNT/C, found in this study, could be
      correlated to previously reported risk factors of EGS. Studies are required to
      determine the predisposing factors that cause EGS, which is apparently not
      present in Israel.

PMID- 17520975
TI  - A region on equine chromosome 13 is linked to recurrent airway obstruction in
      horses.
AB  - REASONS FOR STUDY: Equine recurrent airway obstruction (RAO) is probably
      dependent on a complex interaction of genetic and environmental factors and
      shares many characteristic features with human asthma. Interleukin 4 receptor a
      chain (IL4RA) is a candidate gene because of its role in the development of human
      asthma, confirmation of this association is therefore required. METHODS: The
      equine BAC clone containing the IL4RA gene was localised to ECA13q13 by the FISH
      method. Microsatellite markers in this region were investigated for possible
      association and linkage with RAO in 2 large Warmblood halfsib families. Based on
      a history of clinical signs (coughing, nasal discharge, abnormal breathing and
      poor performance), horses were classified in a horse owner assessed respiratory
      signs index (HOARSI 1-4: from healthy, mild, moderate to severe signs). Four
      microsatellite markers (AHT133, LEX041, VHL47, ASB037) were analysed in the
      offspring of Sire 1 (48 unaffected HOARSI 1 vs. 59 affected HOARSI 2-4) and Sire
      2 (35 HOARSI 1 vs. 50 HOARSI 2-4), age 07 years. RESULTS: For both sires
      haplotypes could be established in the order AHT133-LEXO47-VHL47-ASB37. The
      distances in this order were estimated to be 2.9, 0.9 and 2.3 centiMorgans,
      respectively. Haplotype association with mild to severe clinical signs of chronic
      lower airway disease (HOARSI 2-4) was significant in the offspring of Sire 1 (P =
      0.026) but not significant for the offspring of Sire 2 (P = 0.32). Linkage
      analysis showed the ECA13q13 region containing IL4RA to be linked to equine
      chronic lower airway disease in one family (P<0.01), but not in the second
      family. CONCLUSIONS: This supports a genetic background for equine RAO and
      indicates that IL4RA is a candidate gene with possible locus heterogeneity for
      this disease. POTENTIAL RELEVANCE: Identification of major genes for RAO may
      provide a basis for breeding and individual prevention for this important
      disease.

PMID- 17520976
TI  - Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia
      in horses.
AB  - REASONS FOR PERFORMING STUDY: Endotoxaemia currently is associated with a poor
      prognosis in horses. The results of recent trials in other species indicate that
      phospholipid emulsions reduce the deleterious effects of endotoxin (LPS).
      However, in a previous study in horses, a 2 h infusion of emulsion caused an
      unacceptable degree of haemolysis. HYPOTHESIS: Rapid administration of a lower
      total dose of emulsion would reduce the effects of LPS and induce less
      haemolysis; the emulsion would reduce inflammatory effects of LPS in vitro.
      METHODS: Twelve healthy horses received an i.v. infusion either of saline or a
      phospholipid emulsion (100 mg/kg), followed immediately by E. coli 055:B5 LPS (30
      ng/kg). Clinical parameters, haematological profiles, serum tumour necrosis
      factor (TNF) activity, serum lipid profiles, urine analyses and severity of
      haemolysis were monitored before and at selected times after LPS. Monocytes were
      also incubated in vitro with LPS in the presence or absence of emulsion, after
      which TNF and tissue factor activities were determined. RESULTS: Clinical signs
      of endotoxaemia were reduced in horses receiving the emulsion, including clinical
      score, heart rate, rectal temperature, serum TNF activity, and the characteristic
      leucopenic response to LPS, when compared to horses not receiving the emulsion.
      Three horses receiving the emulsion had none, 2 had mild and one had moderate
      haemolysis. There were no differences in urinalysis results and creatinine
      concentrations, either within the groups over time or between the groups. Serum
      concentrations of phosphatidylcholine, bile acids and triglycerides peaked
      immediately after the infusion; there were no significant changes in
      concentrations of nonesterified fatty acids or cholesterol. Incubation of equine
      monocytes with emulsion prevented LPS-induced TNF and tissue factor activities.
      CONCLUSIONS: Rapid administration of emulsion significantly reduced inflammatory
      effects of LPS in vivo and caused a clinically insignificant degree of
      haemolysis. The results of the in vitro studies indicate that emulsion prevents
      not only LPS-induced synthesis of cytokines, but also expression of membrane
      associated mediators (i.e. tissue factor). POTENTIAL RELEVANCE: Rapid i.v.
      administration of emulsions containing phospholipids that bind endotoxin may
      provide a clinically useful method of treating endotoxaemia in horses.

PMID- 17520977
TI  - Scintigraphic examination of the cartilages of the foot.
AB  - REASONS FOR PERFORMING STUDY: Radiographic examination of the cartilages of the
      foot is well documented; however, there is limited information about their
      scintigraphic assessment. OBJECTIVES: To evaluate the scintigraphic appearance of
      the cartilages of the foot using subjective and quantitative image analysis and
      to correlate radiographic and scintigraphic findings. HYPOTHESES: An ossified
      cartilage would have similar radiopharmaceutical uptake (RU) to the ipsilateral
      aspect of the distal phalanx; RU would extend throughout the length of the
      ossified cartilage; a separate centre of ossification (SCO) would be identified
      on a scintigraphic image; and fracture or trauma to an ossified cartilage would
      manifest as increased RU (IRU). METHODS: Front feet (n = 223) of horses (n = 186)
      that had dorsopalmar radiographic views and dorsal scintigraphic images were
      included in the study. The cartilages of the foot were graded radiographically
      and scintigraphically. Quantitative evaluation of the scintigraphic images was
      carried out using region of interest (ROI) analysis. For statistical analysis RU
      ratios were used. Correlations between a radiographically detected SCO and focal
      RU and between IRU and radiographic abnormalities were assessed. RESULTS: There
      was a good correlation and an excellent agreement between radiographic and
      scintigraphic grades. ROI analysis showed a proximal to distal increase in RU
      ratios within each cartilage of the foot. A radiographically identified SCO could
      be detected scintigraphically in 12/17 feet (70.6%). Thirty-eight feet had IRU in
      the region of a cartilage, 25 of which (65.8%) had corresponding radiographic
      abnormalities. Fracture of an ossified cartilage was associated with IRU in all
      horses. CONCLUSIONS AND POTENTIAL RELEVANCE: Scintigraphy may give information
      about the potential clinical significance of ossification of the cartilages of
      the foot and associated lesions, therefore prompting further investigation by use
      of a uniaxial ipsilateral palmar nerve block and imaging, using either magnetic
      resonance imaging and/or computed tomography.

PMID- 17520978
TI  - Comparison of mandibular motion in horses chewing hay and pellets.
AB  - REASONS FOR PERFORMING STUDY: Previous studies have suggested that
      temporomandibular joint (TMJ) kinematics depend on the type of food being
      masticated, but accurate measurements of TMJ motion in horses chewing different
      feeds have not been published. HYPOTHESIS: The temporomandibular joint has a
      larger range of motion when horses chew hay compared to pellets. METHODS: An
      optical motion capture system was used to track skin markers on the skull and
      mandible of 7 horses as they chewed hay and pellets. A virtual marker was created
      on the midline between the mandibles at the level of the 4th premolar teeth to
      represent the overall motion of the mandible relative to the skull during the
      chewing cycle. RESULTS: Frequency of the chewing cycles was lower for hay than
      for pellets. Excursions of the virtual mandibular marker were significantly
      larger in all 3 directions when chewing hay compared to pellets. The mean
      velocity of the virtual mandibular marker during the chewing cycle was the same
      when chewing the 2 feeds. CONCLUSIONS: The range of mediolateral displacement of
      the mandible was sufficient to give full occlusal contact of the upper and lower
      dental arcades when chewing hay but not when chewing pellets. POTENTIAL
      RELEVANCE: These findings support the suggestion that horses receiving a diet
      high in concentrate feeds may require more frequent dental prophylactic
      examinations and treatments to avoid the development of dental irregularities
      associated with smaller mandibular excursions during chewing.

PMID- 17520979
TI  - In search of clinical truths: equine and comparative studies of anatomy.
AB  - The importance of correlating anatomical studies with diagnostic and therapeutic
      approaches in practice has long been recognised. Such studies in the horse have,
      until recently, lagged behind this discipline in human medicine and surgery.
      Clinical techniques by which this correlation is achieved include radiography,
      ultrasound, computed tomography and magnetic resonance imaging. This review
      presents published literature on the subject and, in addition, describes the part
      played by plastination, a recently developed technique for the preservation of
      biological specimens. In this, tissue fluids and part of the lipids are replaced
      by certain polymers yielding specimens that can be handled without gloves, do not
      smell or decay, and even retain microscopic properties of the original sample.
      The technique has proved to be a useful tool to correct previously presented
      anatomical descriptions and is one now favoured by human surgeons. Studies of the
      horse employing this technique include those of the temporomandibular joint and
      tarsus. The aim of the review is to stimulate further correlations of anatomical
      structure and equine medical and surgical procedures, thereby advancing knowledge
      and understanding in practice and teaching.

PMID- 17520980
TI  - Genes and respiratory disease: a first step on a long journey.
AB  - This review highlights the critical importance of phenotype definition in the
      understanding of the pathogenesis of respiratory disease in horses. The general
      approach to genetic studies is discussed and comparative studies of recurrent
      airway obstruction (RAO) conditions, such as asthma, described in the context of
      learning more about equivalent equine conditions. The availability of methods to
      study genetic tests have previously relied on DNA sequence knowledge from man,
      laboratory and domesticated animals, but recent data from the horse genome
      sequence are now available. This should facilitate advances in the identification
      of specific genes for equine diseases. The review summarises the future potential
      for such studies and places the report in this issue (p 236) by Jost et al.
      (2007) of the involvement of IL4RA as a candidate gene in RAO into this context.

PMID- 17520981
TI  - Statistical approaches to uncertainty: P values and confidence intervals
      unpacked.

PMID- 17520982
TI  - Incisional complications following exploratory celiotomy: does an abdominal
      bandage reduce the risk?
AB  - REASONS FOR PERFORMING STUDY: Post operative complications following exploratory
      laparotomy can be potentially life-threatening, increase post operative morbidity
      and result in an increase in the length of hospitalisation of the affected
      individual. No study has evaluated the efficacy of specific strategies to reduce
      the incidence of post operative incisional complications. HYPOTHESIS: The use of
      an abdominal bandage following colic surgery through a celiotomy incision would
      significantly reduce the prevalence of post operative incisional complications.
      METHODS: A controlled, randomised clinical trial to test the hypothesis was
      devised. Horses eligible for inclusion in the study were assigned randomly either
      to the study or control group following recovery from general anaesthesia. Any
      post operative incisional complications occurring during hospitalisation were
      recorded. Long-term follow-up was obtained via telephone questionnaires. Absolute
      risk reduction (ARR) and number needed to treat (NNT) were calculated.
      Multivariable analyses were conducted for all outcomes of interest. RESULTS:
      There was an ARR of the likelihood of developing a post operative incisional
      complication of 45% when using compared to not using an abdominal bandage in the
      post operative period. Therefore, it would be necessary to treat 2.2 horses with
      an abdominal bandage in order to prevent one horse developing any post operative
      incisional complications. CONCLUSIONS: Although incisional complications continue
      to be a problem following an exploratory celiotomy for colic, the proportion of
      horses affected was significantly reduced by use of a bandage. POTENTIAL
      RELEVANCE: Using an abdominal bandage following an exploratory laparotomy may
      help reduce the prevalence of post operative incisional complications, and
      prevent the development of potentially life-threatening complications.

PMID- 17520983
TI  - Modified live Streptococcus equi ('strangles') vaccination followed by clinically
      adverse reactions associated with bacterial replication.

PMID- 17520984
TI  - The clinical evidence article by Proudman et al. (2007).

PMID- 17520985
TI  - King of pain: what Elvis's death tells us about media coverage of celebrities and
      the pain/addiction interface.

PMID- 17520986
TI  - A comparison of oral midazolam, oral tramadol, and intranasal sufentanil
      premedication in pediatric patients.
AB  - BACKGROUND: This study was designed to evaluate the efficacy and safety of oral
      midazolam, tramadol drops, and intranasal sufentanil for premedication of
      pediatric patients. METHODS: Sixty children, three to 10 years of age, who were
      designated as American Society of Anesthesiologists physical status 1 and who
      were undergoing adenotonsillectomy as inpatients were randomized to receive a
      dosage of 0.5 mg/kg (total of 4 ml) midazolam in cherry juice (n=20, Group M), 3
      mg/kg tramadol drops (n=20, Group T), or 2 microg/kg intranasal sufentanil (n=20,
      Group S). Clinical responses (sedation, anxiolysis, cooperation) and adverse
      effects (respiratory, hemodynamic, etc.) were recorded. Safety was assessed by
      continuous oxygen saturation monitoring and observation. Vital signs (blood
      pressure, pulse, oxygen saturation, respiratory rate) were recorded before drug
      administration (baseline) and then every 10 minutes until the induction of
      anesthesia. RESULTS: Mean blood pressure decreased significantly after five
      minutes of intranasal sufentanil administration relative to Groups M (p < 0.01)
      and T (p < 0.05), whereas heart rate remained unchanged. Oxygen saturation and
      respiratory rate decreased significantly after 20 and 30 minutes of intranasal
      sufentanil administration relative to Groups M and T (p < 0.05). Anxiety scores
      showed rates of 45 percent in Group M, 5 percent in Group T, and 40 percent in
      Group S. Anxiety scores in Groups M and S were better than those of Group T (p <
      0.01). Cooperation scores for face-mask acceptance showed rates of 85 percent in
      Group M, 45 percent in Group T, and 85 percent in Group S (p < 0.01). CONCLUSION:
      Intranasal sufentanil and oral midazolam are more appropriate premedication
      options than tramadol drops in children.

PMID- 17520987
TI  - Urine drug test interpretation: what do physicians know?
AB  - OBJECTIVE: To determine the level of urine drug test (UDT) interpretive knowledge
      of physicians who use these instruments to monitor adherence in their patients on
      chronic opioid therapy. METHODS: A seven-question instrument consisting of six
      five-option, single-best-answer multiple choice questions and one yes/no question
      was completed by 114 physicians (77 who employ UDT and 37 who do not) attending
      one of three regional opioid education conferences. We calculated frequencies and
      performed chi2 analyses to examine bivariate associations between UDT utilization
      and interpretive knowledge. RESULTS: The instrument was completed by 80 percent
      of eligible respondents. None of the physicians who employ UDT answered all seven
      questions correctly, and only 30 percent answered more than half correctly.
      Physicians who employ UDT performed no better on any of the questions than
      physicians who do not employ UDT. CONCLUSIONS: Physicians who employ UDT to
      monitor patients receiving chronic opioid therapy are not proficient in test
      interpretation. This study highlights the need for improved physician education;
      it is imperative for physicians to work closely with certified laboratory
      professionals when ordering and interpreting these tests.

PMID- 17520988
TI  - Psychological factors as predictors of opioid abuse and illicit drug use in
      chronic pain patients.
AB  - BACKGROUND: Psychopathology (depression, anxiety, somatization disorder) and
      substance abuse (opioid misuse and illicit drug use) are common in patients with
      chronic pain and present problems for public health and clinical management.
      Despite a body of literature describing various methods for identifying
      psychopathology, opioid misuse, and illicit drug use in chronic pain patients,
      the relationship between psychopathologies, substance abuse, and chronic pain has
      not been well characterized. METHODS: This report describes a total of 500
      consecutive pain patients prescribed and receiving stable doses of opioids. The
      patients were evaluated for psychopathology, opioid abuse, and illicit drug use
      during the course of regular pain management treatment. The relationships between
      psychopathology and drug abuse and/or illicit drug use in chronic pain patients
      were examined, and psychological evaluation for depression, anxiety, and
      somatization disorder was performed. RESULTS: Depression, anxiety, and
      somatization disorder were documented in 59, 64, and 30 percent of chronic pain
      patients, respectively. Drug abuse was significantly higher in patients with
      depression as compared to patients without depression (12 percent with depression
      versus 5 percent without). Current illicit drug use was higher in women with
      depression (22 percent) than women without depression (14 percent) and in men
      with or without depression (12 percent). Current illicit drug use was also higher
      in men with somatization disorder (22 percent) than men without (9 percent).
      CONCLUSION: This study demonstrated that the presence of psychological features
      of depression and somatization disorder may be markers of substance abuse
      diathesis in chronic pain patients.

PMID- 17520989
TI  - Prevalence and characteristics of breakthrough pain in patients receiving opioids
      for chronic back pain in pain specialty clinics.
AB  - OBJECTIVE: We sought to assess the prevalence and characteristics of breakthrough
      pain (BTP) in patients with chronic back pain. DESIGN: Researchers utilized a
      telephone survey using a pain assessment algorithm. This report represents a
      subset of patients from a larger survey of 228 patients with chronic pain
      unrelated to cancer. PARTICIPANTS: This study employed 117 subjects taking
      opioids for a primary diagnosis of back pain and receiving care at geographically
      dispersed pain treatment centers. Subjects had pain lasting at least six months
      and had "controlled" baseline pain. RESULTS: Eighty-seven subjects (74 percent)
      experienced 93 types of BTP. The median number of BTP episodes per day was two;
      median time to maximum intensity was 10 minutes, and median duration was 55
      minutes. Onset could not be predicted for 46 percent of pains. Eighty-three
      percent of subjects used shorter-acting opioids for BTP. Other medications used
      for pain included NSAIDs, antidepressants, anticonvulsants, skeletal muscle
      relaxants, intrathecal local anesthetics, and transdermal local anesthetics.
      CONCLUSIONS: These patients with opioid-treated chronic back pain commonly
      experienced BTP, which often had a rapid onset and a relatively short duration
      and was difficult to predict. Opioids were the mainstay of pharmacologic therapy,
      but nonopioid analgesics and adjuvant analgesics were commonly used.

PMID- 17520990
TI  - Increasing prevalence of prescription opiate misuse over time among rural
      probationers.
AB  - Prescription opiate misuse is a major public health issue, especially in rural
      areas. The purpose of this analysis was to examine trends in prescription opiate
      misuse over time in a cohort of community-based rural probationers. Participants
      (N=800), recruited over a four-year period, were divided into cohorts according
      to the year in which they were interviewed. Prescription opiate misuse increased
      significantly between 2001 and 2004 (p < 0.001). After adjustment for changes in
      demographic characteristics of the cohorts, misuse of prescription opiates was
      still significantly greater in 2004 compared with 2001. These data suggest
      changes in drug use patterns among community-based rural probationers from street
      to prescription drugs. Implications of the findings are discussed.

PMID- 17520991
TI  - Using methadone to treat opioid-induced hyperalgesia and refractory pain.
AB  - A patient was treated for several years with high doses of opioids for malignant
      pain. During a recent hospitalization, the patient's pain remained uncontrolled
      despite escalating doses of various opioids. We suspected that this patient
      suffered from the clinical phenomenon of opioid-induced hyperalgesia (OIH). The
      patient was then rotated from her other opioids to methadone, and her pain was
      adequately controlled within several days. Methadone, because of its NMDA
      antagonist properties, offers an effective treatment for OIH. The use of
      methadone for analgesia is complex and should be undertaken only by practitioners
      who have appropriate experience.

PMID- 17520992
TI  - Strategies in the prevention and management of ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and
      mortality in the intensive care unit. Prevention of VAP is possible through the
      use of several evidence-based strategies intended to minimize intubation, the
      duration of mechanical ventilation, and the risk of aspiration of oropharyngeal
      pathogens. Current data favor the quantitative analysis of lower respiratory
      tract cultures for the diagnosis of VAP, accompanied by the initiation of broad
      spectrum empiric antimicrobial therapy based on patient risk factors for
      infection with multi-drug-resistant pathogens and data from unit-specific
      antibiograms. Eventual choice of antibiotic and duration of therapy are selected
      based on culture results and patient stability, with an emphasis on minimization
      of unnecessary antibiotic use.

PMID- 17520993
TI  - Perceptions and attitudes of critical care training and careers among United
      States surgical residents: who wants to be a surgical intensivist?
AB  - Less than 50 per cent of surgical critical care (SCC) fellowship positions are
      filled each year. We surveyed senior surgical residents to determine their
      opinions regarding a career in SCC and acute care surgery. A survey was sent to
      1348 postgraduate year 3, 4, and 5 residents in the United States. Two hundred
      fifty-one surveys were returned (19% response rate). Whereas 78 per cent were
      planning to complete a fellowship, 21 per cent expressed interest in SCC. Fifty
      six per cent plan to handle SCC problems only for their own patients, whereas 39
      per cent plan to turn this management over to a critical care provider. SCC
      fellowships were considered to be potentially more appealing if the following
      changes could be made to the existing structure: adding more general surgery (70%
      of respondents); adding more trauma experience (50%); adding emergency
      neurosurgery (44%); adding more emergency orthopedics (42%); or decreasing months
      of critical care (36%). Increasing salary enhanced appeal for 82 per cent. SCC
      has limited appeal for most senior surgical residents. Theoretical expansion of
      surgical critical fellowships to include more general or trauma surgery (acute
      care surgery) increased the level of interest among senior surgical residents.

PMID- 17520994
TI  - If we are too stubborn to ask for directions, then we will still be lost next
      year.

PMID- 17520995
TI  - Tumors at the aortoiliac/inferior vena cava bifurcation: preoperative,
      anesthetic, and intraoperative considerations.
AB  - Primary and recurrent retroperitoneal tumors can involve the aortoiliac
      vasculature. They are often considered inoperable or incurable because of the
      locally advanced nature of the disease or the technical aspects involved in
      safely resecting the lesion. Safe resection of these lesions requires experience
      and extensive preoperative planning for success. A retrospective database review
      of 76 patients with retroperitoneal tumors identified tumors involving major
      vascular structures in the abdomen and pelvis undergoing resection of tumor en
      bloc with the aortoiliac vasculature. Preoperative planning and intraoperative
      technical maneuvers are reviewed. Patients were followed until time of this
      report. Four patients with retroperitoneal tumors involving the aortoiliac
      vessels underwent surgery: two patients with sarcoma (one primary and one
      recurrent), one with metastatic renal cell carcinoma, and one with a
      paraganglioma. All patients had resection of the aorta and vena cava or the iliac
      artery and vein. Arterial reconstruction (anatomic or extra-anatomic) was
      performed in all cases. The patient with renal cell carcinoma also required
      venous reconstruction to support a renal autotransplant. Veno-venous bypass was
      required in one patient. Local control was achieved in 3 of 4 cases. Surgery for
      retroperitoneal tumors involving major vascular structures is technically
      feasible with appropriate planning and technique. Multiple disciplines are
      required, including general surgical oncology, vascular surgery, and possibly,
      cardiothoracic surgery.

PMID- 17520996
TI  - Outcomes of blunt head trauma without intracranial pressure monitoring.
AB  - Although guidelines exist for intracranial pressure (ICP)-guided treatment after
      head trauma, no conclusive data exist that support routine ICP monitoring. A
      retrospective case series was reviewed of all patients admitted to the intensive
      care unit with a diagnosis of blunt head trauma between January 1, 1999 and
      December 31, 2004. None of the patients in the final analysis had ICP monitoring.
      Data collected included age, sex, mechanism of injury, Glasgow Coma Score (GCS)
      at admission, injury severity score, disposition, and length of stay. One hundred
      thirty-one patients with a median age of 41 years were included. There were 104
      men (79%). The median GCS at admission was 12. There were 22 deaths (17%
      mortality). Stepwise logistic regression analysis identified older age, higher
      injury severity score, and lower GCS to be predictors of death. The mortality
      rate was higher in patients with GCS < or =8 compared with GCS >8 (33% vs 8%,
      respectively; P < 0.001). Ten of 23 patients with a GCS of 3 died (43%
      mortality). The median time to death for patients with a GCS of 3 was 2 days.
      Although the Brain Trauma Foundation has published guidelines advocating routine
      ICP monitoring, no large randomized prospective studies are available to
      determine its effect on outcome. None of the patients in this study had ICP
      monitoring. Our overall survival rate of 83 per cent is relatively high. Patients
      with a low GCS and, specifically, those with a GCS of 3 may not benefit from ICP
      monitoring because of early and irreversible trauma. Variability in the use of
      ICP monitoring will remain until ICP monitoring can be conclusively proven to
      improve outcome.

PMID- 17520997
TI  - Fascia: a pragmatic overview for surgeons.
AB  - The term "fascia" is a very frequently used notion, particularly in an
      anatomical, surgical, and radiological context. A closer look at the underlying
      concepts, however, reveals that the denomination is all but a consistent one. It
      is this use of one and the same term for very different entities that is one of
      the sources for controversial opinions on fascial structures and their
      applications in surgical practice. This article summarizes and illustrates
      examples of structures called fasciae. Considering the impossibility to give a
      simple, universal definition, we conclude that a precise description and
      iconographic documentation of the structure under consideration remain mandatory.
      They should replace the presumably unequivocal, but in fact often nebulous,
      notion "fascia" in surgical, radiological, and anatomical articles.

PMID- 17520998
TI  - Poor glycemic control is associated with increased mortality in critically ill
      trauma patients.
AB  - Glycemic control improves outcome in cardiac surgical patients and after
      myocardial infarction or stroke. Hyperglycemic predicts poor outcome in trauma,
      but currently no data exist on the effect of glycemic control in critically ill
      trauma patients. In our intensive care unit (ICU), we use a subcutaneous sliding
      scale insulin protocol to achieve glucose levels <140 mg/dL. We hypothesized that
      aggressive glycemic control would be associated with improved outcome in
      critically ill trauma patients. At our urban Level 1 trauma center, a
      retrospective study was conducted of all injured patients admitted to the
      surgical ICU >48 hours during a 6-month period. Data were collected for mechanism
      of injury, age, diabetic history, Injury Severity Score (ISS), and APACHE II
      score. All blood glucose levels, by laboratory serum measurement or by point-of
      care finger stick, were collected for the entire ICU stay. Outcome data
      (mortality, ICU and hospital length of stay, ventilator days, and complications)
      were collected and analyzed. Patients were stratified by their preinjury diabetic
      history and their level of glucose control (controlled <140 mg/dL vs non
      controlled > or =141 mg/dL) and these groups were compared. During the study
      period, 103 trauma patients were admitted to the surgical ICU >48 hours. Ninety
      (87.4%) were nondiabetic. Most (83.5%) sustained blunt trauma. The average age
      was 50 +/- 21 years, the average ISS was 22 +/- 12, and the average APACHE II was
      16 +/- 9. The average glucose for the population was 128 +/-25 mg/dL. Glycemic
      control was not attained in 27 (26.2%) patients; 19 (70.4%) of these were
      nondiabetic. There were no differences in ISS or APACHE II for controlled versus
      non-controlled patients. However, non-controlled patients were older. Mortality
      was 9.09 per cent for the controlled group and was 22.22 per cent for the non
      controlled group. Diabetic patients were older and less severely injured than
      nondiabetics. For nondiabetic patients, mortality was 9.86 per cent in controlled
      patients and 31.58 per cent in non-controlled patients (P < 0.05). Also, urinary
      tract infections were more prevalent and complication rates overall were higher
      in nondiabetic patients with noncontrolled glucose levels. Nonsurvivors had
      higher average glucose than survivors (P < 0.03). Poor glycemic control is
      associated with increased morbidity and mortality in critically ill trauma
      patients; this is more pronounced in nondiabetic patients. Age may be a factor in
      these findings. Subcutaneous sliding scale insulin alone may be inadequate to
      maintain glycemic control in older critically ill injured patients and in
      patients with greater physiologic insult. Prospective assessment is needed to
      further clarify the benefits of aggressive glycemic control, to assess the
      optimal mode of insulin delivery, and to better define therapeutic goals in
      critically ill, injured patients.

PMID- 17520999
TI  - Increased risk of deep venous thrombosis with endovascular cooling in patients
      with traumatic head injury.
AB  - Endovascular therapeutic hypothermia has been shown to preserve neurological
      function and improve outcomes; however, its use and potential complications have
      not been fully described in patients with traumatic head injuries. We believe
      that the use of endovascular cooling leads to deep venous thrombosis (DVT) in
      this high-risk population. We performed a retrospective review of 11 patients
      with severe head injuries admitted to our Level I trauma center surgical
      intensive care unit who underwent intravascular cooling. Duplex sonograms were
      obtained after 4 days at catheter removal or with clinical symptoms that were
      suspicious for DVT. Patients had a mean age of 23.2 (range, 16-42) years and an
      Injury Severity Score of 31.9 (range, 25-43). The overall incidence of DVT was 50
      per cent. The DVT rate was 33 per cent if catheters were removed in 4 days or
      less and 75 per cent if removed after 4 days (risk ratio = 2.25; odds ratio = 6;
      P = ns). An elevated international normalized ratio upon admission was protective
      against DVT (no DVT = 1.26 vs DVT = 1.09; P = 0.02). Inferior vena cava filters
      were placed in most patients with DVT. The use of endovascular cooling catheters
      is associated with increased risk of DVT in patients with traumatic head
      injuries. Therefore, we discourage the use of endovascular cooling devices in
      this patient population.

PMID- 17521000
TI  - Cardiac impalement from a rib after blunt trauma.
AB  - Blunt chest trauma produces a variety of injuries. We present a case report of a
      hemodynamically stable patient after blunt chest trauma with radiographic images
      suggestive of the left fifth rib penetration to the heart. The diagnosis,
      surgical approach, and course of the patient are discussed.

PMID- 17521001
TI  - An improved method for deploying the polypropylene underlay patch of the PROLENE
      Hernia System.
AB  - The PROLENE Hernia System (PHS) is a bilayer patch device providing an anterior
      approach to preperitoneal inguinal hernia repair. To provide improved expansion
      of the underlay patch of PHS, a modified device featuring a deploying "pocket" in
      the double-layered underlay graft was designed. The deploying "pocket" is flat in
      shape and harbors a perimeter that can act as a receiving unit for surgical
      force, which is exerted outward and backward to expand the underlying graft.
      Through a unique surgical technique using an angled metal pusher to facilitate
      access to intrapocket manipulation, the underlay graft not only can be fully
      deployed, but can be securely placed in the preperitoneal space to cover the
      entire myopectineal orifice. This allows effective treatment of inguinal/femoral
      herniation. Based on the encouraging clinical results obtained using a procedure
      that incorporates this strategy at our hospital, it can be concluded that this
      modified device/technique for PHS is one of the best inguinal/femoral hernia
      repair methods available.

PMID- 17521002
TI  - An economic analysis of hospital charges for choledocholithiasis by different
      treatment strategies.
AB  - The ideal management of presumed choledocholithiasis is controversial. We
      hypothesized that patients admitted with presumed choledocholithiasis would be
      better served financially to undergo laparoscopic cholecystectomy (LC) with
      possible intraoperative intervention versus preoperative endoscopic retrograde
      cholangiopancreatography followed by LC. A chart review was performed from
      September 1, 2000 to August 31, 2003. One hundred seventy-one consecutive
      patients identified with presumed choledocholithiasis were reviewed. Six patients
      were excluded because of missing charge data. Professional and technical fees
      from the total hospital charges were used for comparison. Three groups of
      patients were compared for charge analysis. Group 1 underwent LC with
      laparoscopic common bile duct exploration. Group 2 underwent LC with preoperative
      or postoperative endoscopic retrograde cholangiopancreatography. Group 3 was a
      control group of LC only. Student's t test was used for statistical analysis with
      a P value of <0.05 defined as statistically significant. P values reflect
      comparisons with Group 1. Group 1 charges were $13,026, Group 2 charges were
      $15,303, and Group 3 charges were $9,122. For suspected choledocholithiasis, LC
      with intraoperative intervention is the most economically advantageous approach.

PMID- 17521003
TI  - Giant pelvic solitary fibrous tumor obstructing intestinal and urinary tract: a
      case report and literature review.
AB  - We are reporting a giant pelvic neoplasm, a rare solitary fibrous tumor that
      presented with a large bowel obstruction and bilateral ureteral obstruction
      because of its size and location. Preoperative diagnosis required complex
      pathological studies to exclude a high-grade sarcoma suspected clinically.
      Complete resection was required for resolution of obstructive symptoms. Prognosis
      for solitary fibrous tumors is usually good after complete resection. Recurrence
      and metastasis may be related to rare aggressive histological features, including
      nuclear atypia, hypercellularity, greater than four mitoses/10 high power fields,
      and necrosis. Because histology is not always a reliable predictor of prognosis,
      careful long-term follow-up is necessary for this tumor. Solitary fibrous tumors
      (SFTs) are rare spindle cell neoplasms most likely arising from mesenchymal
      cells. SFTs were originally described in the pleura, the most common site for
      this tumor; however, extrathoracic SFTs are seemingly diagnosed with increased
      frequency. We report a case of a giant pelvic SFT that required complicated
      clinical management.

PMID- 17521004
TI  - The quality of a surgeon defined by internal medicine and family practice
      physicians: a closed-ended survey with importance scale.
AB  - An anonymously completed, closed-ended questionnaire with an importance scale was
      sent to physicians to assess which qualities were important in their selection of
      a surgeon. Differences in proportions of rankings that were designated "extremely
      important" were assessed by binomial logistic regression was used. Null
      hypotheses were rejected if P < 0.05. Forty-two of 61 questionnaires were
      returned for analysis. Differences between dependability and other
      characteristics were statistically significant (G = 35.62, P = 0.001). The only
      characteristics that were statistically significantly less likely to receive a
      ranking of "extremely important" were facility appearance, subspecialty
      fellowship, and graduation from a good residency. All other differences could
      have been explained by chance (P > 0.05). Surgeons' character, equipment, and
      staffing of the facility were ranked extremely important, whereas training of the
      surgeon or the appearance of the facility was not.

PMID- 17521005
TI  - Significance of tumor capsular invasion in well-differentiated thyroid
      carcinomas.
AB  - This study examines the influence of tumor capsular invasion on the biological
      behavior of papillary (PTC) and follicular thyroid carcinoma (FTC) and the
      prognosis of surgically treated patients. This retrospective cohort study
      included 350 cases of PTC or FTC from a university teaching hospital. Patient
      charts were randomly selected and reviewed. The study population was divided into
      PTC and FTC groups. Each group was subdivided into CI+ (with tumor capsular
      invasion) and CI- subgroups (without tumor capsule or without capsular invasion).
      The long-term prognosis was assessed using the American Joint Committee on Cancer
      pTNM staging and the prognostic index was elaborated by the European Organization
      for Research and Treatment of Cancer. There were 284 women and 66 men (ages 19-89
      years, mean of 44) with an incidence of 53.1 per cent for CI+ tumors. There were
      no significant differences between the PTC subgroups regarding the short-term
      clinical outcome and the long-term prognosis. Although patients with CI+ FTC
      showed lower incidence of lymph node metastasis than patients with CI- FTC, the
      FTC subgroups were comparable regarding the short-term clinical outcome and the
      long-term prognosis. Our results suggest that presence of tumor capsular invasion
      does not adversely influence biological behavior or survival of PTC or FTC.
      Moreover, the presence of tumor capsular invasion appears to not have
      significance for the long-term prognosis of patients with PTC or FTC.

PMID- 17521006
TI  - Relevance of group Milleri streptococci in thoracic surgery: a clinical update.
AB  - Group Milleri streptococci (GMS), a heterogeneous group of streptococci, are
      associated with purulent infections. This study was a retrospective analysis of
      all consecutive thoracic infections of GMS between 2001 and 2004. Of 246 surgical
      GMS infections, thoracic infections accounted for 4.5 per cent, including 10
      pleural infections (eight empyemas and two infected pleural effusions) and one
      mediastinal infection. The etiology of pleural infection was parapneumonic (7),
      second to esophageal perforation (1), liver transplantation (1), and liver
      resection (1). Polymicrobial infections were present in 64 per cent. All patients
      underwent removal of the infected masses, including drainage (3), thoracoscopic
      decortication (5), thoracotomy with debridement (2), and incision with drainage
      (1). The case fatality rate was 9 per cent (there was one patient with congestive
      heart disease unfit to undergo surgical empyema evacuation) and the recurrence
      rate was 27.3 per cent (three patients). Combined antibiotic/surgical treatment
      was successful in all other cases. GMS isolates were susceptible to clindamycin
      and all beta-lactam antibiotics except ceftazidime, but were resistant to
      aminoglycosides. If found intrathoracically, GMS frequently progress to severe
      empyema. Therefore, timely removal of pleural collection by percutaneous drainage
      or surgical intervention seems indicated. If surgery is required, thoracoscopic
      decortication may be the preferred approach.

PMID- 17521007
TI  - Partial cholecystectomy as a safe and viable option in the emergency treatment of
      complex acute cholecystitis: a case series and review of the literature.
AB  - Partial cholecystectomy (PC) is an alternative choice to standard cholecystectomy
      in situations with increased risk of Calot's components injury. We reported our
      experience with the patients treated with PC and reviewed the literature. Fifty
      four patients with complex acute cholecystitis underwent PC, including
      conventional partial cholecystectomy (CPC; n = 48) and laparoscopic partial
      cholecystectomy (LPC; n = 6). The clinical diagnosis was verified by
      ultrasonography. In addition, we reviewed 1190 published cases (1972-2005) who
      underwent a "nonconventional" surgery for severe cholecystitis, including
      cholecystostomy, CPC, or LPC. Review of the literature, including our cases,
      showed a male:female ratio of 1.3:1. The major operative indication was severe
      acute cholecystitis. Procedures included cholecystostomy (65.8%) and PC (34.2%).
      In the follow-up (n = 1190), biliary leak (4.8%), retained stones (4.6%),
      recurrent symptoms (2.3%), wound infections (1.9%), persistent biliary fistula
      (0.9%), and prolonged biliary drainage (0.2%) were found, with an overall
      mortality rate of 9.4 per cent. In 133 patients, because of postoperative
      complications (e.g., recurrent symptoms, remaining common bile duct stones, or
      persistence of bile fistula), reoperation was necessary, including 121 cases
      (90.1%) of cholecystectomy, whereas the other 11 patients underwent other
      procedures such as common bile duct exploration or closure of the fistula. The
      surgical trend for complex acute cholecystitis treatment has been changed from
      only cholecystostomy to a spectrum of cholecystostomy, CPC, and LPC with the
      progressive increase of PC. The proportion of the LPC compared with CPC has also
      increased during recent years. It seems that PC is a safe procedure for treating
      complicated acute cholecystitis. Whether the indication and need for alternative
      techniques to standard cholecystectomy is changing should be evaluated in future
      studies.

PMID- 17521008
TI  - Primary biliary B-cell lymphoma of the cystic duct causing obstructive jaundice.
AB  - A distinctive case of primary biliary lymphoma occurring in the cystic duct
      causing extrinsic compression of the porta hepatis in a 48-year-old woman is
      presented. Imaging studies revealed stricture of the common hepatic duct with a
      2.5-cm nonhomogeneous mass at the porta hepatis, mimicking a Klatskin tumor.
      Exploratory laparotomy revealed a mass in the gallbladder neck with extension
      into the cystic duct akin to Mirizzi's syndrome. A soft, tan-yellow 1.0-cm mass
      was removed from the cystic duct, and infiltrating atypical lymphocytic nodules
      were identified with a final diagnosis of an anaplastic variant of diffuse large
      B-cell lymphoma.

PMID- 17521009
TI  - Transabdominal approach for management of Boerhaave's syndrome.
AB  - Several transthoracic approaches have been described for the surgical management
      of Boerhaave's syndrome that carry their own morbidity in patients who can be
      systemically unwell at presentation, and best practice is not established. We
      introduce a novel transabdominal approach to manage the perforation and spare
      these patients the trauma of a thoracotomy. Four patients with spontaneous
      esophageal rupture were managed using a transabdominal approach. Postoperative
      complications, length of intensive care unit stay, postoperative hospital stay,
      time to oral intake, and morbidity and mortality were used as outcome measures.
      After operation, the median intensive care unit stay was 4 days (range, 0-5) in
      patients who required a median of 10.5 days (range, 6-17) to establish oral
      intake. One patient required a transthoracic drainage of an empyema and one
      patient required percutaneous drainage of a mediastinal collection. The median
      length of stay was 38 days and there was zero mortality. The transabdominal
      approach is safe and effective for the management of Boerhaave's syndrome and
      should be considered in the treatment paradigm for this condition. Intrathoracic
      complications account for postoperative morbidity.

PMID- 17521010
TI  - Patch repair of ileoanal pouch-vaginal fistula with Permacol collagen implant.
AB  - Though uncommon, ileoanal pouch-vaginal fistulas after restorative
      proctocolectomy present quite a challenge. Multiple salvage procedures, including
      endoanal, transabdominal, and trans-vaginal, have been used. Because of high
      recurrence rates, multiple operations are not uncommon, and ultimate pouch
      failure rates have been reported as high as 45 per cent. The Permacol Collagen
      Implant is a surgical implant that has been used successfully in a variety of
      operations ranging from urological to maxillofacial. Its properties allow
      fibroblast infiltration and revascularization so that it gradually becomes
      permanently incorporated into the surrounding tissue, providing strength and
      inhibiting scarring and contraction. We report the first documented case of
      Permacol use in repair of ileoanal pouch-vaginal fistula and we feel that it
      warrants further investigation as an option in the treatment of these fistulas.

PMID- 17521011
TI  - Captive tiger attack: case report and review of the literature.
AB  - Tigers, as well as other large predators, are being held in private settings with
      increasing frequency. Unregulated private "zoos" are cropping up in many rural
      and suburban settings across the country. The number of attacks from captive
      predators also is on the rise. This case highlights the potentially violent and
      aggressive nature of wild animals held in captivity. Treatment principals and
      wounding patterns of large cat attacks are emphasized.

PMID- 17521012
TI  - Diagnosis and minimally invasive resection of an insulinoma: report of an unusual
      case and review of the literature.
AB  - Insulinomas are rare endocrine tumors that are usually diagnosed by inappropriate
      elevations in insulin and C-peptide during hypoglycemia. We report a case of a
      surgically confirmed insulinoma diagnosed by a mild elevation in proinsulin with
      suppressed insulin and C-peptide at the time of hypoglycemia during a supervised
      fast. A supervised fast with serial measurements of plasma glucose, insulin, and
      C-peptide was performed in a patient with documented hypoglycemia. Proinsulin was
      measured at the beginning and end of the fast. Tumor localization was
      accomplished with spiral CT, magnetic resonance imaging, and endoscopic
      ultrasound. Minimally invasive tumor resection was performed. The presence of an
      insulinoma was confirmed on the basis of a minimally elevated proinsulin level
      with a suppressed insulin level at the time of symptomatic hypoglycemia. Tumor
      resection was performed without complications, resulting in resolution of the
      hypoglycemia. This case demonstrates the importance of measuring proinsulin as a
      routine component of the 72-hour fast for detection of an insulinoma. Even mild
      elevations in circulating proinsulin can be an independent indicator of aberrant
      insulin secretion during hypoglycemia. Once the diagnosis of insulinoma is made
      and tumor localization is achieved, minimally invasive tumor resection is a safe
      and effective treatment modality.

PMID- 17521013
TI  - Accessory breasts: a historical and current perspective.
AB  - The presence of accessory breast tissue such as extra nipples (polythelia) and
      extra breast (polymastia) is relatively common, with a high incidence of being
      misdiagnosed in clinical medicine. Although polythelia is congenital in origin
      and is identifiable at childhood, polymastia may not be evident until the
      influence of sex hormones during puberty. In this article, we present a review of
      the literature concerning the historical background of accessory breasts, their
      incidence, their misdiagnoses, and their association with other syndromes and
      diseases. Finally, we present the common treatment options available today for
      such conditions.

PMID- 17521014
TI  - Into the ears of babes....

PMID- 17521015
TI  - The chaos in health care financing.

PMID- 17521016
TI  - Health care transparency.

PMID- 17521017
TI  - True pay for performance.

PMID- 17521018
TI  - Managing overhead.

PMID- 17521019
TI  - Fixing the five 'failure points' that short-circuit cash flow. Case study.

PMID- 17521020
TI  - Whose job is it?
AB  - One of the biggest challenges administrators face is convincing everyone else in
      the practice that issues such as patient safety and patient satisfaction are the
      administrator's concern, too. An administrator can lead the way to dramatic
      improvements in patient satisfaction, access to providers and profitability-
      often starting when he or she makes an effective pitch to influential physicians
      in the practice. Administrators at three medical practices describe their efforts
      to make their organizations patient-centered.

PMID- 17521021
TI  - Good, better, best.
AB  - Medical group administrators are challenged to focus on quality management
      because of increasing external accreditation requirements and industry interest
      in pay-for-performance programs, patient safety and outcomes measurement. But
      which management approach do you use, and how do you get started? The author
      describes how the Baldrige Health Care Criteria for Performance Excellence serve
      as a quality management framework to lead organizational change in a medical
      practice.

PMID- 17521022
TI  - It is TOO my money!
AB  - The Centers for Medicare & Medicaid Services' final rule regarding changes to the
      Medicare appeal procedures--some of which affect physicians--recently took
      effect. The authors advise physician groups undergoing Medicare audits to
      understand the new appeals process and the strategies available to them. They
      describe the four-level appeal process and outline legal and other strategies
      that physician groups can use to appeal a denial.

PMID- 17521023
TI  - On the cover. Dawn redwood.

PMID- 17521024
TI  - Pediatric and adolescent HIV disease.
AB  - OBJECTIVE: To review the current literature and guidelines for pediatric and
      adolescent human immunodeficiency virus (HIV) diagnosis and treatment. DATA
      SOURCES: MEDLINE and the Centers for Disease Control and Prevention Web sites
      were searched to obtain relevant articles. STUDY SELECTION: The expert opinions
      of the authors were used to design cases that highlight the studies and
      guidelines reviewed. RESULTS: There have been numerous advances in the
      prevention, diagnosis, and treatment of pediatric and adolescent HIV disease in
      the past decade. Now, HIV is a chronic illness managed with medication, when
      appropriate. The HIV transmission rate from mother to child is very low
      (approximately 1%) in industrialized countries because antiretroviral agents are
      now available to pregnant women. The pill burden for children and adults with HIV
      has plummeted from 8 to 10 pills 3 times daily to 3 to 5 pills once daily in the
      best-case scenarios. A shift has occurred in HIV care from treating opportunistic
      illnesses to promoting adherence and avoiding drug resistance while monitoring
      medication adverse effects. CONCLUSIONS: Diagnosis and treatment of HIV is a
      rapidly changing field with frequently changing guidelines. The coming years may
      bring already available technology to the rest of the world and advances toward
      the prevention and cure of HIV.

PMID- 17521025
TI  - Duration of allergen immunotherapy in respiratory allergy: when is enough,
      enough?
AB  - OBJECTIVES: To investigate the duration of effective inhalant subcutaneous
      immunotherapy (SCIT) reported in the published literature and to determine if any
      specific biomarkers or clinical predictors exist that may identify patients who
      will remain in long-term remission after discontinuing treatment. DATA SOURCES:
      Articles were selected from a search of the PubMed database from 1976 to 2006
      using the search terms immunotherapy and allergen immunotherapy in combination
      with venom, allergic rhinitis, asthma, mechanism, efficacy, and duration, as well
      as articles known to the authors and referenced in review articles. STUDY
      SELECTION: Articles were selected if evaluation of efficacy of the primary
      allergic disease treated after discontinuation of SCIT was stated as one of the
      objectives of the study. RESULTS: The rate of relapse after discontinuing SCIT
      ranges from 0% to 55% of patients in the studies reviewed in this article. The
      length of the specific allergen immunotherapy and allergen type (ie, perennial vs
      seasonal) may be variables that affect the duration of clinical remission after
      cessation of SCIT. One study found the duration of SCIT efficacy after
      discontinuation depended on duration of treatment and correlated with decrease in
      skin test reactivity. CONCLUSION: Until specific tests or clinical markers are
      identified that will clearly distinguish between patients who will relapse from
      those who will remain in long-term clinical remission after discontinuing
      effective allergen immunotherapy, the decision to continue or stop immunotherapy
      must be individualized.

PMID- 17521026
TI  - Risk factors for wheezing in early adolescence: a prospective birth cohort study
      in Brazil.
AB  - BACKGROUND: Many asthma studies are available in the literature, but few
      investigated whether risk factors for asthma differ by sex. OBJECTIVE: To
      evaluate risk factors for wheezing in early adolescence, with emphasis on sex
      differences. METHODS: A prospective birth cohort study was initiated in 1993;
      87.5% of the original cohort was traced at 11 years, totaling 4,452 adolescents.
      Current wheezing was defined as at least 1 crisis in the previous 12 months. The
      following independent variables were analyzed: maternal smoking during pregnancy,
      wheezing at 4 years, maternal wheezing, and adolescent body mass index. RESULTS:
      Current wheezing affected 13.5% (95% confidence interval [CI], 12.4%-14.5%) of
      the cohort. The prevalence of current wheezing was 15.3% (95% CI, 13.7%-16.8%) in
      boys and 11.7% (95% CI, 10.4%-13.1%) in girls (P < .001). Maternal smoking was
      related to an increased risk of wheezing for boys but not for girls. There was a
      significant tracking of wheezing from 4 to 11 years in both sexes, although the
      magnitude was stronger for boys. A dose-response association between maternal
      wheezing and adolescent wheezing was observed in boys but not in girls. Finally,
      obesity was associated with an increased risk of wheezing in boys but not in
      girls. CONCLUSIONS: The variables explored in this investigation had a stronger
      effect on adolescent wheezing in boys than in girls. Public health strategies
      aimed at minimizing the burden of wheezing should take these sex differences into
      account.

PMID- 17521027
TI  - Screening for poor short-term outcome in acute pediatric asthma.
AB  - BACKGROUND: Despite good initial treatment response, many children with acute
      asthma exacerbations have poor short-term outcomes. OBJECTIVE: To develop and
      validate a risk score to screen for poor short-term outcome at the time of
      emergency department (ED) treatment. METHODS: Prospective cohort study of
      children treated for acute asthma at 2 pediatric EDs. Poor 14-day outcome was
      defined as any of the following: asthma symptoms still above baseline at 14 days,
      child missed 5 or more days of school or day care, caretaker missed 5 or more
      days of school or work, or unscheduled care or admission after the ED visit for
      worsening symptoms. RESULTS: A total of 1,221 children were enrolled: 852 at the
      derivation site and 369 at the validation site. Five variables independently
      associated with poor outcome by logistic regression were used to create a simple
      linear score: wheezing 2 or more days before the visit, 3 or more acute
      outpatient asthma visits in the previous 12 months, home use of albuterol,
      history of severe persistent asthma, and fever at the ED visit. Area under the
      receiver operating characteristic curve values were 0.66/0.67 for the
      derivation/validation samples. Two or more features categorized high risk. The
      test characteristics for the derivation/validation samples are as follows:
      sensitivity, 0.67/0.62; specificity, 0.61/0.68; likelihood ratio, 1.7/1.9;
      pretest probability, 33%/47%; and posttest probability, 50%/62%. CONCLUSIONS:
      Information available at the ED visit was used to develop a simple risk score
      that identifies patients at high risk for poor outcome. The score would be useful
      in evaluating interventions to improve outcomes by allowing interventions to be
      targeted to a subgroup most likely to benefit.

PMID- 17521028
TI  - Inverse association between rural environment in infancy and sensitization to
      rodents in adulthood.
AB  - BACKGROUND: It is not known whether early childhood exposure to hygiene
      hypothesis factors modifies the risk of sensitization to aeroallergens among
      adults. Studying adults exposed to allergens in the workplace may help determine
      whether childhood exposures confer lasting protection against sensitization.
      OBJECTIVE: To determine whether early life exposures influence the prevalence of
      sensitization to allergens in adulthood. METHODS: Sensitization to rodents was
      determined by skin testing in a cross-sectional study among university employees
      with and without occupational exposure to laboratory animals. Demographic
      information was obtained by questionnaire. RESULTS: Of 137 employees, 8% of
      workers without occupational exposure to laboratory animals and 24% of those with
      such exposure were sensitized to rodents (P = .007). None of 32 study
      participants who lived in a rural environment during their first year of life
      were rodent sensitized vs 18% of those who lived in other settings (P < .01).
      Rural setting in infancy was also associated with a decreased prevalence of
      sensitization to outdoor allergens (odds ratio [OR], 0.36; 95% confidence
      interval [CI], 0.14-0.95). After adjusting for multiple confounders,
      sensitization to rodents remained rare among individuals who lived in a rural
      setting during infancy (OR, <0.15). Rodent sensitization was more prevalent among
      those with higher educational attainment (OR, 9.50; 95% CI, 1.10-82.02) and those
      sensitized to indoor allergens (OR, 6.22; 95% CI, 1.42-27.24). Sensitization to
      rodents was not significantly associated with having older siblings or
      sensitization to outdoor allergens. CONCLUSIONS: Living in a rural setting during
      the first year of life is associated with protection from sensitization to rodent
      allergens in the workplace decades later.

PMID- 17521029
TI  - Environmental tobacco smoke and the epidemic of asthma in children: the role of
      cigarette use.
AB  - BACKGROUND: Asthma is the most common chronic disease affecting youth worldwide.
      The prevalence of asthma has increased at least 3-fold during the past several
      decades. The reason for this increase remains unknown. OBJECTIVE: To examine one
      possible factor that may be affecting the increase in prevalence of asthma among
      youth. METHODS: Data on the incidence of asthma among youth were aggregated using
      the National Health Interview Survey (sample of 4,500 children) and were compared
      on an ecologic level with data on cigarette consumption in the United States from
      1900 to 2003 from the American Lung Association. RESULTS: Our results suggest a
      parallel increase in the rates of cigarette use among adults and asthma in
      children. These findings show an increase in cigarette use during the past 4
      birth cohorts, with subsequent leveling off at a population level with a
      progressively more prominent increase in cigarette use among women in the United
      States. CONCLUSION: We present one possible factor that may be contributing to
      the epidemic of childhood asthma. We hypothesize that (1) there has been a marked
      increase in smoking during the past century, (2) this increase in smoking has
      resulted in a substantial increase in exposure to environmental tobacco smoke
      among children, and (3) increased exposure to environmental tobacco smoke has
      contributed to the increase in childhood asthma. Data on trends in cigarette use
      among adults and asthma prevalence among children during the past century are
      presented as ecological evidence in support of this hypothesis. Future studies
      will be needed to confirm these findings with community-level analyses in a
      variety of geographic regions.

PMID- 17521030
TI  - Traffic and outdoor air pollution levels near residences and poorly controlled
      asthma in adults.
AB  - BACKGROUND: Air pollution may exacerbate asthma. OBJECTIVE: To investigate
      associations between traffic and outdoor air pollution levels near residences and
      poorly controlled asthma among adults diagnosed as having asthma in Los Angeles
      and San Diego counties, California. METHODS: We estimated traffic density within
      500 ft of 2001 California Health Interview Survey respondents' reported
      residential cross-street intersections. Additionally, we assigned annual average
      concentrations of ozone, nitrogen dioxide, particulate matter 2.5 and 10
      micrometers or less in diameter, and carbon monoxide measured at government
      monitoring stations within a 5-mile radius of the reported residential cross
      street intersections. RESULTS: We observed a 2-fold increase in poorly controlled
      asthma (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.38-3.23) among
      asthmatic adults in the highest quintile of traffic density after adjusting for
      age, sex, race, and poverty. Similar increases were seen for nonelderly adults,
      men, and women, although associations seemed strongest in elderly adults (OR,
      3.00; 95% CI, 1.13-7.91). Ozone exposures were associated with poorly controlled
      asthma among elderly adults (OR, 1.70; 95% CI, 0.91-3.18 per 1 pphm) and men (OR,
      1.76; 95% CI, 1.05-2.94 per 1 pphm), whereas particulate matter 10 micrometers or
      less seemed to affect primarily women (OR, 2.06; 95% CI, 1.17-3.61), even at
      levels below the national air quality standard. CONCLUSIONS: Heavy traffic and
      high air pollution levels near residences are associated with poorly controlled
      asthma.

PMID- 17521031
TI  - Comparison of the allergenicity and Ole e 1 content of 6 varieties of Olea
      europaea pollen collected during 5 consecutive years.
AB  - BACKGROUND: Numerous varieties of Olea europaea have been described in
      Mediterranean countries. OBJECTIVE: To investigate the immunochemical
      characteristics of 6 varieties of Olea europaea collected during 5 consecutive
      years. METHODS: The varieties Carrasquefio, Manzanillo, Acebuche (wild olive),
      Hojiblanco, Picual, and Nevado were analyzed. Pollen samples from each variety
      were collected for 5 consecutive years from the same cultivars by trained
      personnel. The antigenic and allergenic profiles of these extracts were evaluated
      by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western
      blot using the serum of 29 O. europaea-allergic individuals. Ole e 1 was measured
      using enzyme-linked immunosorbent assay and purified Ole e 1 and rabbit
      polyclonal antibodies. Allergenic potency was determined using enzyme-linked
      immunosorbent assay inhibition and is expressed in histamine equivalent prick
      units per gram of raw material. RESULTS: Hojiblanco and Acebuche had the lowest
      mean +/- SD Ole e 1 content in the 5 years (0.045 +/- 0.029 and 0.059 +/-0.031
      microg/microg of freeze-dried material, respectively). The variety with the
      highest mean +/- SD Ole e 1 content was Picual (0.19 +/-0.075 microg/microg).
      Hojiblanco had the lowest total biological potency throughout the study. A
      positive correlation was obtained between rainfall in the winter months and total
      allergenicity of the 6 varieties. CONCLUSIONS: The different varieties of O.
      europaea pollen demonstrated great differences in allergenic potency and Ole e 1
      content. These differences were maintained throughout the study, suggesting that
      they are due to genetic differences intrinsic to the varieties, although certain
      climatic effects may also play a role.

PMID- 17521032
TI  - An in vivo and in vitro comparison of inhaled steroid delivery via a novel vortex
      actuator and a conventional valved holding chamber.
AB  - BACKGROUND: Valved holding chambers improve delivery of inhaled corticosteroids
      to the lung but are bulky in design. A novel compact vortex actuator device has
      therefore been developed. OBJECTIVES: To compare the in vitro and in vivo
      performance of a novel compact vortex actuator (the Neohaler [NH]) vs a
      conventional small-volume valve holding chamber (the AeroChamber Plus [AP].
      METHODS: Seventeen asthmatic patients completed the study per protocol, receiving
      4 weeks each of 100 microg/d (50-microg formulation) or 400 microg/d (100-microg
      formulation) of hydrofluoroalkane beclomethasone dipropionate via the NH or AP
      devices in a randomized crossover, double-blind, double-dummy, placebo-controlled
      design. The doubling dilution (dd) shift in methacholine provocation
      concentration that caused a decrease in forced expiratory volume in 1 second of
      20% (primary outcome) was used to evaluate anti-inflammatory effects and adrenal
      function to measure systemic exposure. The fine particle (<4.7 tm) dose was
      evaluated using an Andersen Cascade Impactor. RESULTS: A total of 100 microg of
      hydrofluoroalkane beclomethasone dipropionate via the NH and AP produced 0.95-dd
      (95% confidence interval [CI], 0.44-1.45; P = .006) and 0.45-dd (95% CI, -0.16 to
      1.06; P = .83) improvements from baseline in methacholine provocation
      concentration that caused a decrease in forced expiratory volume in 1 second of
      20%, respectively, with no statistically significant difference between devices:
      0.50 dd (95% CI, -0.25 to 1.24; P = .18). At 400 microg/d, 1.08-dd (95% CI, 0.49
      1.67; P = .006) and 0.85-dd (95% CI, 0.32-1.39; P = .02) improvements were found
      for the NH and AP, respectively, with a 0.23-dd difference (95% CI, -0.28 to
      0.74; P = .36) between devices. No adrenal suppression occurred with either
      device. The in vitro fine particle dose was 39.1 microg for the NH and 39.0
      microg for the AP with the 100-microg formulation and 26.0 g and 25.2 microg,
      respectively, with the 50-microg formulation. CONCLUSIONS: Delivering
      hydrofluoroalkane beclomethasone dipropionate via the NH and AP attenuates
      asthmatic airway inflammation to a comparable degree and produces a similar in
      vitro fine particle dose profile.

PMID- 17521033
TI  - Currant allergy and the Rosaceae-grass pollen allergy syndrome: a case report.
AB  - BACKGROUND: Despite the increasing use of currants in culinary recipes, currant
      allergy has rarely been reported. OBJECTIVES: To study a case of currant allergy
      and to explore cross-reactivity between grass pollen and Rosaceae family fruit
      allergens. METHODS: Skin prick tests to pollen and skin prick-to-prick tests with
      currants and peach were performed. Specific IgE levels were determined using the
      CAP method. We prepared a protein extract of 0.1 mg/mL in phosphate-buffered
      saline using red currant in the presence of protease inhibitors. Immunoblot
      inhibition studies were performed to explore cross-reactivity between grass
      pollen and currant allergens. RESULTS: Skin prick test results were positive to
      Dactylis, arizonic, and olive pollens. Results of skin prick-to-prick tests with
      fresh red and black currants were negative and positive, respectively, to peach.
      The specific IgE level was 5.7 KU/L to red currant and 2.92 KU/L to peach (CAP).
      Western blot analysis with red currant extract revealed specific IgE protein
      bands of 37 and 26 kDa. Preincubation of sera with extracts from red currant and
      peach inhibited both IgE bands, and preincubation with Dactylis pollen inhibited
      the 37-kDa band only. CONCLUSIONS: We report a case of allergy to grass pollen
      with an oral allergy syndrome involving several fruits from 2 different families
      of the Rosidae subclass confirmed by in vitro tests. Inhibition studies
      demonstrated cross-reactivity between different fruits (currant and raspberry)
      from the Rosidae subclass and were incomplete with grass pollen allergens.

PMID- 17521034
TI  - Progressive multifocal leukoencephalopathy in a patient with common variable
      immunodeficiency and abnormal CD8+ T-cell subset distribution.
AB  - BACKGROUND: Patients with primary hypogammaglobulinemia have been reported to
      have encephalopathy, but progressive multifocal leukoencephalopathy (PML) due to
      JC virus reactivation is a rare cause. OBJECTIVE: To provide the clinical details
      and case discussion of a patient diagnosed as having common variable
      immunodeficiency (CVID) who has progressive neurodegenerative symptoms and was
      found to have PML and an abnormal CD8+ T-cell subset distribution. METHODS: A
      detailed case report providing the patient's immunodeficiency history, diagnostic
      evaluation, and medical management and a review of related literature. RESULTS:
      Before his neurodegenerative illness, the patient was found to have
      hypogammaglobulinemia, poor specific antibody responses, low circulating B-cell
      levels, and abnormal delayed-type hypersensitivity responses; there was no Bruton
      tyrosine kinase (BTK) mutation. The PML was diagnosed using brain biopsy and was
      confirmed using a DNA probe specific for JC virus. Peripheral blood flow
      cytometry at the time of PML diagnosis revealed an accumulation of naive CD8+ T
      cells (CD3+CD8+CD45RA+) and a deficiency of memory CD8+ T-cell subsets
      (CD3+CD8+CD45RA- or CD3+CD8+CD45RO+). Despite aggressive treatment with
      interleukin 2, interferon-gamma, and intravenous cidofovir, the patient died.
      CONCLUSIONS: JC virus infection should be considered in the differential
      diagnosis of the patient with CVID and signs and symptoms of encephalopathy. The
      role of this patient's abnormal CD8' T-cell subset distribution in the
      development or control of this rare infection is worthy of consideration and has
      encouraged us to enumerate naive and memory CD4+ and CD8+ T-cell subsets in
      patients diagnosed as having CVID, even in the absence of neurodegenerative
      symptoms.

PMID- 17521035
TI  - Primary gastrointestinal lymphangiectasia presenting as cryptococcal meningitis.
AB  - BACKGROUND: Opportunistic infections commonly occur in immunocompromised
      patients; however, it is unusual for an adult to present with a combined cellular
      and humoral immunodeficiency. Cryptococcal meningitis is a fatal condition if
      untreated and is usually found in patients with cellular immunodeficiency.
      OBJECTIVE: To report the case of an adult patient with cryptococcal meningitis
      secondary to intestinal lymphangiectasia. METHODS: A 59-year-old man was admitted
      to the hospital for disseminated cryptococcal meningitis and osteomyelitis.
      Laboratory evaluation, computed tomography, esophagogastroduodenoscopy, and
      biopsy were performed. RESULTS: Laboratory evaluation revealed a lymphopenia,
      hypoalbuminemia, hypogammaglobulinemia, and negative human immunodeficiency virus
      test results by enzyme-linked immunosorbent assay and polymerase chain reaction.
      The complete blood cell count, urinalysis, serum and urine protein
      electrophoresis, and functional antibody responses to protein and polysaccharide
      antigens were normal. Results of computed tomography of the chest, abdomen, and
      pelvis were unremarkable. Multiple lymphangiectasias were visualized with
      esophagogastroduodenoscopy and confirmed by biopsy. The patient was treated with
      intravenous amphotericin B and flucytosine, and the meningitis resolved.
      CONCLUSIONS: Based on a computerized search of the medical literature, this is
      the first description of cryptococcal meningitis secondary to intestinal
      lymphangiectasias. The combination of lymphopenia, hypogammaglobulinemia, and
      hypoalbuminemia should alert the clinician to the possibility of intestinal
      lymphangiectasias and the potential for immune dysfunction.

PMID- 17521036
TI  - Sea urchin roe (uni) anaphylaxis.
AB  - BACKGROUND: Sea urchin roe, a Japanese and Korean delicacy served with sushi, has
      not been previously described as a food allergen. OBJECTIVE: To determine the
      specific cause of anaphylaxis that occurred while eating a sushi meal consisting
      of crackling shrimp, California roll with snow crab and sea urchin roe (uni),
      cooked eel (unagi) with fish sauce, rice, and saki mayo. METHODS: Allergy
      percutaneous skin testing, serum IgE testing via the Pharmacia ImmunoCAP system,
      and fresh eel and sea urchin roe food testing were performed. RESULTS: Allergy
      evaluation included negative skin testing to shrimp, lobster, crab, oyster, clam,
      scallop, tuna, salmon, and cod. Pharmacia ImmunoCAP testing did not detect any
      specific IgE to oyster, crab, shrimp, blue mussel, lobster, clam, scallop, or eel
      (allergen specific IgE <0.35 KU/L). Fresh sea urchin roe skin prick testing
      yielded a 16-mm wheal and a 25-mm flare (histamine positive control: 7-mm wheal
      and 10-mm flare). Results of fresh eel skin prick testing were similar to those
      of the saline negative control. CONCLUSIONS: This case represents the first
      reported episode of sea urchin roe anaphylaxis. Consideration and investigation
      of novel food allergens may decipher causes of unexplained, food-related
      anaphylaxis.

PMID- 17521037
TI  - Allergen immunotherapy in a patient with human immunodeficiency virus: effect on
      T-cell activation and viral replication.
AB  - BACKGROUND: Allergen immunotherapy is a major therapeutic modality in the
      treatment of allergic rhinitis. However, with T-cell activation potential, its
      role in patients with human immunodeficiency virus (HIV) was theoretically
      limited. OBJECTIVE: To report the results of allergen immunotherapy in a patient
      with HIV treated with highly active antiretroviral therapy (HAART). METHODS: A 44
      year-old man with a history of HIV did not respond to medical therapy for
      allergic rhinitis. His HIV status was well controlled with HAART. Owing to the
      severity of his allergic rhinitis symptoms, he accepted the risk of allergy
      immunotherapy despite the unknown effect of immunotherapy in patients with HIV.
      RESULTS: After 6 weeks of weekly immunotherapy injections, his viral load
      remained undetectable and his CD4 cell count changed from 540 to 570
      cells/microL. After 16 weeks of weekly immunotherapy, his viral load increased to
      10,900 copies/mL, and his CD4 cell count increased to 665 cells/microL. After 24
      weeks of weekly immunotherapy, his viral load returned to an undetectable level,
      and his CD4 cell count stabilized at 356 cells/microL. Despite his notable change
      in HIV status, he continues to receive the same HAART. He currently continues en
      route to maintenance immunotherapy. CONCLUSIONS: The effect of allergen
      immunotherapy on HIV infection has not been previously reported. A concern
      remains that any form of immunotherapy may negatively affect HIV disease
      progression. This case illustrates that weekly allergen immunotherapy may have
      induced limited T-cell proliferation and a modest increase in RNA viral load,
      which resolved with continuation of HAART.

PMID- 17521038
TI  - Methacholine PC20: 1-point formula.

PMID- 17521039
TI  - Interpretation of pneumococcal vaccine response.

PMID- 17521040
TI  - Genetic polymorphisms of the novel FCERIA gene region: relation to total serum
      IgE levels.

PMID- 17521041
TI  - Normal IgG and IgA levels in IgM-deficient patients: a review of 93 cases.

PMID- 17521043
TI  - Distorted Born diffraction tomography applied to inverting ultrasonic field
      scattered by noncircular infinite elastic tube.
AB  - This study focuses on the application of ultrasonic diffraction tomography to
      noncircular 2D-cylindrical objects immersed in an infinite fluid. The distorted
      Born iterative method used to solve the inverse scattering problem belongs to the
      class of algebraic reconstruction algorithms. This method was developed to
      increase the order of application of the Born approximation (in the case of
      weakly-contrasted media) to higher orders. This yields quantitative information
      about the scatterer, such as the speed of sound and the attenuation. Quantitative
      ultrasonic imaging techniques of this kind are of great potential value in fields
      such as medicine, underwater acoustics and nondestructive testing.

PMID- 17521042
TI  - Frame rate considerations for real-time abdominal acoustic radiation force
      impulse imaging.
AB  - With the advent of real-time Acoustic Radiation Force Impulse (ARFI) imaging,
      elevated frame rates are both desirable and relevant from a clinical perspective.
      However, fundamental limitations on frame rates are imposed by thermal safety
      concerns related to incident radiation force pulses. Abdominal ARFI imaging
      utilizes a curvilinear scanning geometry that results in markedly different
      tissue heating patterns than those previously studied for linear arrays or
      mechanically-translated concave transducers. Finite Element Method (FEM) models
      were used to simulate these tissue heating patterns and to analyze the impact of
      tissue heating on frame rates available for abdominal ARFI imaging. A perfusion
      model was implemented to account for cooling effects due to blood flow and frame
      rate limitations were evaluated in the presence of normal, reduced and negligible
      tissue perfusions. Conventional ARFI acquisition techniques were also compared to
      ARFI imaging with parallel receive tracking in terms of thermal efficiency.
      Additionally, thermocouple measurements of transducer face temperature increases
      were acquired to assess the frame rate limitations imposed by cumulative heating
      of the imaging array. Frame rates sufficient for many abdominal imaging
      applications were found to be safely achievable utilizing available ARFI imaging
      techniques.

PMID- 17521044
TI  - Spectral and scatterer-size correlation during angular compounding: simulations
      and experimental studies.
AB  - In a previous study, theoretical expressions were derived for the correlation
      between ultrasonic scatterer-size estimates and their associated spectral
      measures when echo data are acquired from the same location but at different
      angles. The results were verified using simulations. In the present work, we
      further analyze simulation data for these conditions; in addition, we measure the
      correlations using a cylindrical tissue-mimicking phantom. Experimental and
      theoretical results show that the relationship of scatterer-size correlation to
      insonification angle depends on gate duration, gate type and beam profile. Some
      discrepancies are noted between experimental results and theoretical predictions,
      particularly when using smaller gated windows. The sources of the discrepancies
      are discussed. Experimental results using a 6-MHz linear array suggest that, to
      save acquisition and processing time while reducing variance, a 2 degree-3 degree
      angular increment step provides efficient angular compounding for scatterer-size
      imaging with this array. Theoretical predictions can provide estimates of
      expected correlations between angular acquisitions when compounding with other
      transducers.

PMID- 17521045
TI  - Real-time stereo 3D ultrasound.
AB  - Real-time 3D ultrasound was developed at Duke University in 1991 and has since
      been used with a variety of transducers and shown effectiveness in clinical
      applications and in vivo animal imaging studies. Methods for displaying the 3D
      pyramid of data acquired by the system include selecting 2D image slices or
      integrating data into a volume rendered view. A third method, real-time stereo 3D
      imaging, is discussed here. The clinical commercial 3D system has been modified
      in our laboratory to display a real-time stereo image pair on the scanner display
      to be viewed through a stereoscope. This merges the pair into a single image,
      with a sensation of depth. Stereoscopic displays have previously been
      demonstrated to provide benefits, including improved depth judgments and
      increased perception of image quality in other applications. Previously-saved
      volumes of ultrasound data are shown in stereo 3D using the new system.

PMID- 17521046
TI  - Telemedicine offers new alternatives for behavioral healthcare delivery.

PMID- 17521047
TI  - Surefire strategies to boost DM enrollment and retention.
AB  - Experts share their success stories in reaching and engaging a much bigger
      percentage of their targeted population.

PMID- 17521048
TI  - Aggressive outreach and intervention deliver major dividends regarding at-risk
      pregnant women.
AB  - See how a Medicaid health plan in Rochester, NY, took a step-by-step approach
      toward better birth outcomes.

PMID- 17521049
TI  - New report calls for action on diabetes and its complications.
AB  - Get serious about diabetes and its complications. That's what a new report says
      is necessary to get this troubling disease under control. The latest data about
      costs and prevalence are truly alarming and, in response, a consortium of
      organizations has lined up to help providers and patients take meaningful steps
      toward change.

PMID- 17521050
TI  - Computed tomographic measurement of gluteal subcutaneous fat thickness in
      reference to failure of gluteal intramuscular injections.
AB  - OBJECTIVE: Casual observation of gluteal region fat thickness on computed
      tomography (CT) of the pelvis leads to the hypothesis that, in some individuals,
      intended intramuscular injections are not properly deposited in the gluteal
      muscle. We gathered and analyzed data to determine whether this hypothesis was
      true. METHODS: CT scans of the pelvis were analyzed over an 18-day period in the
      fall of 2005. The thickness of gluteal region subcutaneous fat was measured in a
      standardized manner. RESULTS: Measurement of gluteal region subcutaneous fat
      thickness was performed for 298 pelvic CT scans. There were 150 male subjects and
      148 female subjects. The average gluteal fat thickness for female subjects was
      33.2 mm, whereas the average for male subjects was 23.1 mm. Analysis revealed a
      significant difference in gluteal region fat thickness between male and female
      subjects. A 37-mm needle, allowing for 6-mm penetration of the gluteal muscle,
      would not have entered the gluteal muscle fibres in 81 of 148 female subjects
      (54.7%), in 21 of 150 male subjects (14%), and in 102 of the 298 total sample
      (34.2%). Analysis revealed a significant difference between male and female
      subjects with regard to gluteal muscle needle penetration. CONCLUSION AND
      RECOMMENDATION: An overall predicted failure rate of 34% was identified for
      intended gluteal intramuscular injections when the standard technique was used.
      This is important information for care providers who inject medications in the
      gluteal region. In a significant number of patients, the medications will be
      injected subcutaneously and not into the gluteal musculature, possibly altering
      the pharmacokinetics of the administered medication. An alternative injection
      site should probably be chosen to increase the success rate of intramuscular
      deposition of medications and vaccines in unselected adults.

PMID- 17521051
TI  - Imaging management of spontaneous giant esophageal intramural hematoma.
AB  - A woman, aged 84 years, presented to our emergency department with posteriorly
      radiating chest pain that began following dinner. She reported no change in bowel
      habits, hematochezia, or melena. She had previous peptic ulcer disease and a long
      standing history of gastroesophageal reflux disease. Her medications included
      acetylsalicylic acid and rabeprazole. Electrocardiogram and troponin analyses
      were negative for ischemic heart disease. The emergency physician suspected an
      aortic dissection, and computed tomography (CT) chest and abdomen scans were
      performed with and without IV and oral contrast. The aorta was normal and the
      noncontrast images demonstrated a hyperdense mass (not shown) that did not
      enhance consistent with a large intramural hematoma extending from the upper
      esophagus (level of T2 vertebral body) to the fundus of the stomach (Figures 1A
      and B).

PMID- 17521052
TI  - Canadian Association of Radiologists: consensus guidelines for the prevention of
      contrast-induced nephropathy.
AB  - The development of acute renal failure significantly complicates intravascular
      contrast medium (CM) use and is linked with high morbidity and mortality. The
      increasing use of CM, an aging population, and an increase in chronic kidney
      disease (CKD) will result in an increased incidence of contrast-induced
      nephropathy (CIN)-unless preventive measures are used. The Canadian Association
      of Radiologists has developed these guidelines as a practical approach to risk
      stratification and prevention of CIN. The major risk factor predicting CIN is
      preexisting CKD, which can be predicted from the glomerular filtration rate
      (GFR). In terms of being an absolute measure, serum creatinine (SCr) is an
      unreliable measure of renal function. Patients with GFR >60 mL/min have a very
      low risk of CIN, and preventive measures are generally unnecessary. When GFR is
      <60 mL/min, preventive measures should be instituted. The risk of CIN is greatest
      in patients with GFR <30 mL/min. Preventive measures: Alternative imaging that
      does not require CM should be considered. Fluid volume loading is the single most
      important protective measure. Nephrotoxic medications should be discontinued 48
      hours prior to the study. CM volume and frequency of administration should be
      minimized, but satisfactory image quality should still be maintained. High
      osmolar contrast should be avoided in patients with renal impairment. There is
      some evidence to suggest that iso-osmolar contrast reduces the risk of CIN among
      patients with renal impairment, but further study is necessary to determine
      whether iso-osmolar contrast is superior to low-osmolar contrast. Acetylcysteine
      (AC) has been advocated to reduce the incidence of CIN; however, not all studies
      have shown a benefit, and it is difficult to formulate evidence-based
      recommendations at this time. Its use may be considered in high-risk patients but
      is not considered mandatory.

PMID- 17521053
TI  - Do turf wars kill patients?
AB  - While physicians are often heard to complain that they are overworked with a
      heavy patient burden, so-called turf wars lurk under the surface, wherein
      physicians wrangle for the ability to perform what are generally highly
      remunerated and quickly-performed procedures and interventions with excellent
      patient outcomes. It is very possible that within such turf wars, one specialty
      is consistently more skilled at performing the procedure than another, and
      therefore patient lives may be unnecessarily lost. This article hypothesizes that
      such differences in skills do exist between specialties and proposes a study to
      determine this.

PMID- 17521054
TI  - Coronary computed tomography angiography: overview of technical aspects, current
      concepts, and perspectives.
AB  - Multidetector-row electrocardiogram (ECG)-gated cardiac computed tomography (CT)
      will probably be a major noninvasive imaging option in the near future. Recent
      developments indicate that this new technology is improving rapidly. This article
      presents an overview of the current concepts, perspectives, and technical
      capabilities in coronary CT angiography (CTA). We have reviewed the recent
      literature on the different applications of this technology; of particular note
      are the many studies that have demonstrated the high negative predictive value
      (NPV) of coronary CTA, when performed under optimal conditions, for significant
      stenoses in native coronary arteries. This new technology's level of performance
      allows it to be used to evaluate the presence of calcified plaques, coronary
      bypass graft patency, and the origin and course of congenital coronary anomalies.
      Despite a high NPV, the robustness of the technology is limited by arrhythmias,
      the requirement of low heart rates, and calcium-related artifacts. Some
      improvements are needed in the imaging of coronary stents, especially the smaller
      stents, and in the detection and characterization of noncalcified plaques.
      Further studies are needed to more precisely determine the role of CTA in various
      symptomatic and asymptomatic patient groups. Clinical testing of 64-slice
      scanners has recently begun. As the technology improves, so does the spatial and
      temporal resolution. To date, this is being achieved through the development of
      systems with an increased number of detectors and shorter gantry rotation time,
      as well as the development of systems equipped with 2 X-ray tubes and the
      eventual development of flat-panel technology. Thus further improvement of image
      quality is expected.

PMID- 17521055
TI  - Imaging features of unusual intracranial cystic meningiomas.
AB  - OBJECTIVE: To describe the imaging features of unusual intracranial cystic
      meningiomas in infants and adults. METHODS: We retrospectively reviewed the
      magnetic resonance and computed tomography findings for 2 female patients and 3
      male patients, ranging in age from 1 to 73 years (median 41 years), with
      histopathologically proven cystic meningioma. RESULT: Although cystic meningiomas
      usually appear as solid and cystic masses, they may present as a mainly
      multicystic lesion. The wall of a cystic part of the meningioma may include both
      enhancing and unenhancing areas at imaging. The cystic portion of a meningioma is
      hypointense on diffusion-weighted images and markedly hyperintense on
      corresponding apparent diffusion coefficient maps. CONCLUSION: Cystic meningiomas
      may vary in appearance at imaging. They can be very challenging when present in
      infants. Knowledge of imaging findings and awareness of variability in the
      differential diagnosis can help to avoid preoperative diagnostic pitfalls.

PMID- 17521056
TI  - Answer to case of the month #117. Follicular cyst in surgically transposed ovary
      of young woman with Hodgkin's disease.

PMID- 17521057
TI  - Answer to case of the month #118. Flexor tendon pulley injury.

PMID- 17521058
TI  - Screening mammography--caveat venditor.

PMID- 17521059
TI  - Upping the ante: how does the need for evidence-based practice influence Neonatal
      Network articles?

PMID- 17521060
TI  - Proceed with caution: using Wikipedia as a reference.

PMID- 17521061
TI  - Subdural and primary subarachnoid hemorrhages: a case study.
AB  - Subdural hemorrhage (SDH) and primary subarachnoid hemorrhage (SAH) are two forms
      of intracranial bleeding that can be encountered in infants. These events can be
      life threatening to the infant and devastating to his family. Neonatal nurses
      need to have an understanding of these unfortunate, yet not uncommon, types of
      intracranial hemorrhage. This article explains the etiology, the diagnosis, and
      the treatment of SDH and SAH, concluding

PMID- 17521062
TI  - Evaluation of the impact of the S.T.A.B.L.E. Program on the pretransport care of
      the neonate.
AB  - PURPOSE: To determine whether the S.T.A.B.L.E. Program increases health care
      providers' confidence and clinical abilities in pretransport stabilization and to
      assess the care of transported neonates before and after S.T.A.B.L.E. Program
      education. DESIGN: A descriptive design was used to evaluate health care
      providers ' confidence about pretransport stabilization and to assess infant
      outcomes before and after S.T.A.B.L.E. education. SAMPLE: Sixty-four participants
      in the S.T.A.B.L.E. Program in Nova Scotia participated in this study over a 13
      month period. Thestudy evaluated the charts of all neonates transported tothe IWK
      Health Centre over two one-year periods, before and after the S.T.A.B.L.E.
      Program. MAIN OUTCOME VARIABLE: Perceived confidence and incorporation of
      S.T.A.B.L.E. Program principles among regional health care provide:rs and
      neonatal stability at time of transfer were measured. RESULTS: Ninety-six percent
      of participants indicated that the course was relevant and useful. Ninety percent
      indicated that they felt more confident about their ability to provide neonatal
      pretransport stabilization, and 86.5 percent reported adoptionof the S.T.A.B.L.E.
      Program principles into their practice. There were no differences in infant
      outcomes between the pre- and post-S.T.A.B.L.E. time periods.

PMID- 17521063
TI  - Use of the six sigma methodology to reduce incidence of breast milk
      administration errors in the NICU.
AB  - Breast milk is the optimal source of nutrition for infants. According to
      research, neonates fed breast milk have a reduced risk of sepsis, increased
      feeding tolerance, a decreased incidence of necrotizing enterocolitis, and better
      neurodevelopmental outcomes. Unfortunately, researchers have not identified
      practices to reduce or eliminate the risk for errors in breast milk
      administration. This article discusses the potential hazards of incorrect
      administration of breast milk. It then describes how the tertiary care center at
      Children's Hospital of Illinois implemented a policy utilizing six sigma quality
      improvement methodologies to improve breast milk administration. Since
      implementation of this policy, the NICU at our hospital has reduced the risk of
      breast milk administration errors to less than 3.4 mistakes per million
      opportunities.

PMID- 17521064
TI  - Use of the Duotron transporter high frequency ventilator during neonatal
      transport.
AB  - In the past, transport of neonates with severe respiratory failure was hampered
      by the lack of an appropriate transport ventilator capable of providing high
      frequency ventilation (HFV). This article reports on the experiences of the
      Intermountain Health Care Life Flight Program in selecting a high frequency
      ventilator and preparing the transport team members for its use. Once the use of
      the Duotron ventilator was initiated, pre- and posttransport data were collected
      for the first 134 neonates requiring HFV on transport. Analysis of the data
      determined that 96 percent of the infants were successftslly transported using
      the Duotron ventilator. Inspired oxygen requirements staved the same or improved
      in the majority of intubated patients for whom comparison data xvere available.
      Ventilation and acid-base balance improved. Although HFV has been a common
      therapy in neonatal care for some time, its adoption for use during transport
      required modification and considerable education for transport team members.

PMID- 17521065
TI  - Safety and efficacy of ibuprofen versus indomethacin for the treatment of patent
      ductus arteriosus in the preterm infant: reviewing the evidence.

PMID- 17521066
TI  - Ebstein's anomaly.

PMID- 17521067
TI  - A community-based approach to influenza assessment and treatment during a
      pandemic.
AB  - In the event of an influenza pandemic, hospitals and community-based health
      services will be overwhelmed. To ensure that life-saving health services are able
      to continue, the Ontario Health Plan for an Influenza Pandemic (OHPIP) provides
      direction for assessing and treating patients with influenza, remotely and
      through the implementation of alternate assessment, treatment and referral
      centres (Flu Centres). The OHPIP also provides tools and resources for local
      pandemic planners to assist them with the implementation of this strategy.

PMID- 17521068
TI  - Influenza pandemic planning: one organization's experience.
AB  - This article highlights influenza pandemic planning by a geriatric facility in
      order to ensure preparedness for staff, clients and families. By describing our
      experience, we hope that other facilities that provide geriatric, long-term care
      services are able to advance their own pandemic plans.

PMID- 17521069
TI  - Pandemic influenza planning for children and youth: who's looking out for our
      kids?
AB  - Recent worldwide attention on influenza pandemics has mainly focused on planning
      and preparation. Some published plans appear to have missed some unique
      considerations relevant to children and youth, leaving a serious and potentially
      devastating gap in our pandemic response. This paper highlights those unique
      considerations and encourages health administrators and policy-makers to rise to
      the challenge and demonstrate leadership by ensuring that all institutions
      consider children and youth in their pandemic planning.

PMID- 17521070
TI  - Health systems planning for an influenza pandemic.
AB  - District planning, in general, and influenza pandemic planning, in particular,
      are necessary to sustain health care organizations and systems. An extensive
      stakeholder process used by Capital District Health Authority (CDHA) and the
      Izaak Walton Killam (IWK) Health Centre involved more than 25 teams. This work
      resulted in a joint CDHA/IWK pandemic influenza contingency plan for public
      health, primary care, acute care and tertiary care services. In addition,
      district and business continuity planning has been enhanced.

PMID- 17521071
TI  - Organizational ethics and the management of health care organizations.

PMID- 17521072
TI  - Should health care providers be given earlier access to prophylaxis during a
      pandemic?

PMID- 17521074
TI  - Fuzzy receiver operating characteristic curve: an option to evaluate diagnostic
      tests.
AB  - Traditional receiver operating characteristic (ROC) analysis is widely utilized
      to evaluate diagnostic tests but it is restricted to dichotomous results. The aim
      of this study is to develop the "fuzzy receiver operating characteristic"
      methodology combining the fuzzy sets theory and the traditional ROC methodology,
      and to utilize this new tool to evaluate a diagnostic test. We review traditional
      ROC analysis in mathematical language that utilizes crisp sets and rewrites it
      based on fuzzy sets. Fuzzy ROC analysis is used to evaluate a fuzzy-rule-based
      system (FRBS) developed to predict the pathological stage of a prostate cancer in
      its ability to discriminate between two states: organ-confined and non-confined.
      Traditional ROC analysis is insufficient to evaluate this system because the
      result is given in possibilistic terms. The methodology developed in this work is
      a generalization of the dichotomous ROC analysis, and appears to better represent
      the performance of diagnostic tests that include a degree of uncertainty similar
      to the one presented here.

PMID- 17521073
TI  - Medical informatics and bioinformatics: a bibliometric study.
AB  - This paper reports on an analysis of the bioinformatics and medical informatics
      literature with the objective to identify upcoming trends that are shared among
      both research fields to derive benefits from potential collaborative initiatives
      for their future. Our results present the main characteristics of the two fields
      and show that these domains are still relatively separated.

PMID- 17521075
TI  - Three-dimensional touch interface for medical education.
AB  - We present the technical principle and evaluation of a multimodal virtual reality
      (VR) system for medical education, called a touch simulator. This touch simulator
      comes with an innovative three-dimensional (3-D) touch sensitive input device.
      The device comprises a six-axis force-torque sensor connected to a tangible
      object representing the shape of an anatomical structure. Information related to
      the point of contact is recorded by the sensor, processed, and audiovisually
      displayed. The touch simulator provides a high level of user-friendliness and
      fidelity compared to other purely graphically oriented simulation environments.
      In this paper, the touch simulator has been realized as an interactive
      neuroanatomical training simulator. The user can visualize and manipulate
      graphical information of the brain surface or different cross-sectional slices by
      a finger-touch on a brain-like shaped tangible object. We evaluated the system by
      theoretical derivations, experiments, and subjective questionnaires. In the
      theoretical analysis, we could show that the contact point estimation error
      mainly depends on the accuracy and the noise of the sensor, the amount and
      direction of the applied force, and the geometry of the tangible object. The
      theoretical results could be validated by experiments: applying a normal force of
      10 N on a 120 mm x 120 mm x 120 mm cube causes a maximum error of 2.5 +/- 0.7 mm.
      This error becomes smaller when increasing the contact force. Based on the survey
      results, the touch simulator may be a useful tool for assisting medical schools
      in the visualization of brain image data and the study of neuroanatomy.

PMID- 17521076
TI  - Mining three-dimensional anthropometric body surface scanning data for
      hypertension detection.
AB  - Hypertension is a major disease, being one of the top ten causes of death in
      Taiwan. The exploration of three-dimensional (3-D) anthropometry scanning data
      along with other existing subject medical profiles using data mining techniques
      becomes an important research issue for medical decision support. This research
      attempts to construct a prediction model for hypertension using anthropometric
      body surface scanning data. This research adopts classification trees to reveal
      the relationship between a subject's 3-D scanning data and hypertension disease
      using the hybrid of the association rule algorithm (ARA) and genetic algorithms
      (GAs) approach. The ARA is adopted to obtain useful clues based on which the GA
      is able to proceed its searching tasks in a more efficient way. The proposed
      approach was experimented and compared with a regular genetic algorithm in
      predicting a subject's hypertension disease. Better computational efficiency and
      more accurate prediction results from the proposed approach are demonstrated.

PMID- 17521077
TI  - A new system for computer-aided preoperative planning and intraoperative
      navigation during corrective jaw surgery.
AB  - A new system for computer-aided corrective surgery of the jaws has been developed
      and introduced clinically. It combines three-dimensional (3-D) surgical planning
      with conventional dental occlusion planning. The developed software allows
      simulating the surgical correction on virtual 3-D models of the facial skeleton
      generated from computed tomography (CT) scans. Surgery planning and simulation
      include dynamic cephalometry, semi-automatic mirroring, interactive cutting of
      bone and segment repositioning. By coupling the software with a tracking system
      and with the help of a special registration procedure, we are able to acquire
      dental occlusion plans from plaster model mounts. Upon completion of the surgical
      plan, the setup is used to manufacture positioning splints for intraoperative
      guidance. The system provides further intraoperative assistance with the help of
      a display showing jaw positions and 3-D positioning guides updated in real time
      during the surgical procedure. The proposed approach offers the advantages of 3-D
      visualization and tracking technology without sacrificing long-proven cast-based
      techniques for dental occlusion evaluation. The system has been applied on one
      patient. Throughout this procedure, we have experienced improved assessment of
      pathology, increased precision, and augmented control.

PMID- 17521078
TI  - Approximate entropy-based epileptic EEG detection using artificial neural
      networks.
AB  - The electroencephalogram (EEG) signal plays an important role in the diagnosis of
      epilepsy. The EEG recordings of the ambulatory recording systems generate very
      lengthy data and the detection of the epileptic activity requires a time
      consuming analysis of the entire length of the EEG data by an expert. The
      traditional methods of analysis being tedious, many automated diagnostic systems
      for epilepsy have emerged in recent years. This paper proposes a neural-network
      based automated epileptic EEG detection system that uses approximate entropy
      (ApEn) as the input feature. ApEn is a statistical parameter that measures the
      predictability of the current amplitude values of a physiological signal based on
      its previous amplitude values. It is known that the value of the ApEn drops
      sharply during an epileptic seizure and this fact is used in the proposed system.
      Two different types of neural networks, namely, Elman and probabilistic neural
      networks, are considered in this paper. ApEn is used for the first time in the
      proposed system for the detection of epilepsy using neural networks. It is shown
      that the overall accuracy values as high as 100% can be achieved by using the
      proposed system.

PMID- 17521079
TI  - A wavelet approach for the identification of axonal synaptic varicosities from
      microscope images.
AB  - Direct visualization of synapses is a prerequisite to the analysis of the spatial
      distribution patterns of synaptic systems. Such an analysis is essential to the
      understanding of synaptic circuitry. In order to facilitate the visualization of
      individual synapses at the subcellular level from microscope images, we have
      introduced a wavelet-based approach for the semiautomated recognition of axonal
      synaptic varicosities. The proposed approach to image analysis employs a family
      of redundant wavelet representations. They are specifically designed for the
      recognition of signal peaks, which correspond to the presence of axonal synaptic
      varicosities. In this paper, the two-dimensional image of an axon together with
      its synaptic varicosities is first transformed into a one-dimensional (1-D)
      profile in which the axonal varicosities are represented by peaks in the signal.
      Next, by decomposing the 1-D profile in the differential wavelet domain, we
      employ the multi-scale point-wise product to distinguish between peaks and
      noises. The ability to separate the true signals (due to synaptic varicosities)
      from noise makes possible a reliable and accurate recognition of axonal synaptic
      varicosities. The proposed algorithms are also designed with a variable threshold
      that effectively allows variable sensitivities in varicosity detection. The
      algorithm has been systematically validated using images containing varicosities
      (< or =30) that have been consistently identified by seven human observers. The
      proposed algorithm can give high sensitivity and specificity with appropriate
      threshold. The results have indicated that the semiautomatic approach is
      satisfactory for processing a variety of microscopic images of axons under
      different conditions.

PMID- 17521080
TI  - Optimal coding of vectorcardiographic sequences using spatial prediction.
AB  - This paper discusses principles, implementation details, and advantages of
      sequence coding algorithm applied to the compression of vectocardiograms (VCG).
      The main novelty of the proposed method is the automatic management of distortion
      distribution controlled by the local signal contents in both technical and
      medical aspects. As in clinical practice, the VCG loops representing P, QRS, and
      T waves in the three-dimensional (3-D) space are considered here as three
      simultaneous sequences of objects. Because of the similarity of neighboring
      loops, encoding the values of prediction error significantly reduces the data set
      volume. The residual values are de-correlated with the discrete cosine transform
      (DCT) and truncated at certain energy threshold. The presented method is based on
      the irregular temporal distribution of medical data in the signal and takes
      advantage of variable sampling frequency for automatically detected VCG loops.
      The features of the proposed algorithm are confirmed by the results of the
      numerical experiment carried out for a wide range of real records. The average
      data reduction ratio reaches a value of 8.15 while the percent root-mean-square
      difference (PRD) distortion ratio for the most important sections of signal does
      not exceed 1.1%.

PMID- 17521081
TI  - Confident interpretation of Bayesian decision tree ensembles for clinical
      applications.
AB  - Bayesian averaging (BA) over ensembles of decision models allows evaluation of
      the uncertainty of decisions that is of crucial importance for safety-critical
      applications such as medical diagnostics. The interpretability of the ensemble
      can also give useful information for experts responsible for making reliable
      decisions. For this reason, decision trees (DTs) are attractive decision models
      for experts. However, BA over such models makes an ensemble of DTs
      uninterpretable. In this paper, we present a new approach to probabilistic
      interpretation of Bayesian DT ensembles. This approach is based on the
      quantitative evaluation of uncertainty of the DTs, and allows experts to find a
      DT that provides a high predictive accuracy and confident outcomes. To make the
      BA over DTs feasible in our experiments, we use a Markov Chain Monte Carlo
      technique with a reversible jump extension. The results obtained from clinical
      data show that in terms of predictive accuracy, the proposed method outperforms
      the maximum a posteriori (MAP) method that has been suggested for interpretation
      of DT ensembles.

PMID- 17521082
TI  - Knowledge-driven multidimensional indexing structure for biomedical media
      database retrieval.
AB  - Today, biomedical media data are being generated at rates unimaginable only years
      ago. Content-based retrieval of biomedical media from large databases is becoming
      increasingly important to clinical, research, and educational communities. In
      this paper, we present the recently developed entropy balanced statistical (EBS)
      k-d tree and its applications to biomedical media, including a high-resolution
      computed tomography (HRCT) lung image database and the first real-time protein
      tertiary structure search engine. Our index utilizes statistical properties
      inherent in large-scale biomedical media databases for efficient and accurate
      searches. By applying concepts from pattern recognition and information theory,
      the EBS k-d tree is built through top-down decision tree induction.
      Experimentation shows similarity searches against a protein structure database of
      53 363 structures consistently execute in less than 8.14 ms for the top 100 most
      similar structures. Additionally, we have shown improved retrieval precision over
      adaptive and statistical k-d trees. Retrieval precision of the EBS k-d tree is
      81.6% for content-based retrieval of HRCT lung images and 94.9% at 10% recall for
      protein structure similarity search. The EBS k-d tree has enormous potential for
      use in biomedical applications embedded with ground-truth knowledge and
      multidimensional signatures.

PMID- 17521083
TI  - A novel method of language modeling for automatic captioning in TC video
      teleconferencing.
AB  - We are developing an automatic captioning system for teleconsultation video
      teleconferencing (TC-VTC) in telemedicine, based on large vocabulary
      conversational speech recognition. In TC-VTC, doctors' speech contains a large
      number of infrequently used medical terms in spontaneous styles. Due to
      insufficiency of data, we adopted mixture language modeling, with models trained
      from several datasets of medical and nonmedical domains. This paper proposes
      novel modeling and estimation methods for the mixture language model (LM).
      Component LMs are trained from individual datasets, with class n-gram LMs trained
      from in-domain datasets and word n-gram LMs trained from out-of-domain datasets,
      and they are interpolated into a mixture LM. For class LMs, semantic categories
      are used for class definition on medical terms, names, and digits. The
      interpolation weights of a mixture LM are estimated by a greedy algorithm of
      forward weight adjustment (FWA). The proposed mixing of in-domain class LMs and
      out-of-domain word LMs, the semantic definitions of word classes, as well as the
      weight-estimation algorithm of FWA are effective on the TC-VTC task. As compared
      with using mixtures of word LMs with weights estimated by the conventional
      expectation-maximization algorithm, the proposed methods led to a 21% reduction
      of perplexity on test sets of five doctors, which translated into improvements of
      captioning accuracy.

PMID- 17521084
TI  - Bagging linear sparse Bayesian learning models for variable selection in cancer
      diagnosis.
AB  - This paper investigates variable selection (VS) and classification for biomedical
      datasets with a small sample size and a very high input dimension. The sequential
      sparse Bayesian learning methods with linear bases are used as the basic VS
      algorithm. Selected variables are fed to the kernel-based probabilistic
      classifiers: Bayesian least squares support vector machines (BayLS-SVMs) and
      relevance vector machines (RVMs). We employ the bagging techniques for both VS
      and model building in order to improve the reliability of the selected variables
      and the predictive performance. This modeling strategy is applied to real-life
      medical classification problems, including two binary cancer diagnosis problems
      based on microarray data and a brain tumor multiclass classification problem
      using spectra acquired via magnetic resonance spectroscopy. The work is
      experimentally compared to other VS methods. It is shown that the use of bagging
      can improve the reliability and stability of both VS and model prediction.

PMID- 17521085
TI  - Multiple abdominal organ segmentation: an atlas-based fuzzy connectedness
      approach.
AB  - Organ segmentation is an important step in various medical image applications. In
      this paper, a presegmented atlas is incorporated into the fuzzy connectedness
      (FC) framework for automatic segmentation of abdominal organs. First, the atlas
      is registered onto the subject to provide an initial segmentation. Then, a novel
      method is applied to estimate the necessary FC parameters such as organ intensity
      features, seeds, and optimal FC threshold automatically and subject adaptively.
      In order to overcome the intensity overlapping between the neighboring organs, a
      shape modification approach based on Euclidean distance and watershed
      segmentation is used. This atlas-based segmentation method has been tested on
      some abdominal CT and MRI images from Chinese patients. Experimental results
      indicate the validity of this segmentation method for various image modalities.

PMID- 17521086
TI  - Morphological granulometric features of nucleus in automatic bone marrow white
      blood cell classification.
AB  - The proportion of counts of different types of white blood cells in the bone
      marrow, called differential counts, provides invaluable information to doctors
      for diagnosis. Due to the tedious nature of the differential white blood cell
      counting process, an automatic system is preferable. In this paper, we
      investigate whether information about the nucleus alone is adequate to classify
      white blood cells. This is important because segmentation of nucleus is much
      easier than the segmentation of the entire cell, especially in the bone marrow
      where the white blood cell density is very high. In the experiments, a set of
      manually segmented images of the nucleus are used to decouple segmentation
      errors. We analyze a set of white-blood-cell-nucleus-based features using
      mathematical morphology. Fivefold cross validation is used in the experiments in
      which Bayes' classifiers and artificial neural networks are applied as
      classifiers. The classification performances are evaluated by two evaluation
      measures: traditional and classwise classification rates. Furthermore, we compare
      our results with other classifiers and previously proposed nucleus-based
      features. The results show that the features using nucleus alone can be utilized
      to achieve a classification rate of 77% on the test sets. Moreover, the
      classification performance is better in the classwise sense when the a priori
      information is suppressed in both the classifiers.

PMID- 17521087
TI  - The joint expeditionary medicine specialist.

PMID- 17521088
TI  - Post-traumatic stress disorder and depression in health care providers returning
      from deployment to Iraq and Afghanistan.
AB  - OBJECTIVE: This study examines risk factors for post-traumatic stress disorder
      (PTSD), depression, and mental health care use among health care workers deployed
      to combat settings. METHODS: Anonymous surveys were administered to previously
      deployed workers at a military hospital. PTSD and depression were assessed by
      using the PTSD Checklist and the Patient Health Questionnaire depression scale,
      respectively. Deployment exposures and perceived threats during deployment were
      also assessed. RESULTS: There were 102 respondents (36% response rate). Nine
      percent (n=9) met the criteria for PTSD and 5% (n=5) met the criteria for
      depression. Direct and perceived threats of personal harm were risk factors for
      PTSD; exposure to wounded or dead patients did not increase risk. Those who met
      the criteria for PTSD were more likely to seek mental health care after but not
      before their deployment. CONCLUSIONS: For health care workers returning from a
      warfare environment, threat of personal harm may be the most predictive factor in
      determining those with subsequent PTSD.

PMID- 17521089
TI  - Long-term course of post-traumatic stress disorder (PTSD) in German soldiers:
      effects of inpatient eye movement desensitization and reprocessing therapy and
      specific trauma characteristics in patients with non-combat-related PTSD.
AB  - OBJECTIVE: In this study, we retrospectively evaluated a patient population of 89
      German soldiers who received inpatient treatment for post-traumatic stress
      disorder at the German Armed Forces Hospital in Hamburg from 1998 to 2003.
      METHODS: Patients were nonrandomly assigned to a treatment group who received eye
      movement desensitization and reprocessing and a comparison group with general
      hospital treatment and relaxation training. Follow-up information was obtained 29
      months post-treatment. Trauma-related symptoms were assessed using the Impact of
      Event Scale and the Post-Traumatic Stress Scale (PTSS-10) as parameters of
      improvement. RESULTS: The Impact of Event Scale showed that inpatient trauma
      therapy with eye movement desensitization and reprocessing significantly improved
      the course of post-traumatic stress disorder. In addition, the Impact of Event
      Scale indicated a significantly poorer long-term outcome for patients who had
      been confronted with death during their traumatic experience. Other factors
      tested were of no significant influence. CONCLUSIONS: These results may influence
      further treatment strategies for traumatized German soldiers.

PMID- 17521090
TI  - Receipt of disability through an outreach program for homeless veterans.
AB  - Receipt of public support payments is associated with beneficial outcomes for
      homeless people with mental illness. The purpose of this study was to identify
      factors associated with receipt of Department of Veterans Affairs (VA) pension
      and compensation benefits among homeless veterans after their initial contact
      with the VA national homeless outreach program. We examined data for 5731
      veterans who were contacted by the program during the first 3 months of fiscal
      year 2003 and who were not receiving VA benefits, and we documented their benefit
      status over a minimum of 18 months. A limited number of veterans (15%) were
      subsequently awarded benefits; they were more likely to have reported recent use
      of VA services and a greater number of medical and psychiatric problems at the
      time of outreach. Findings suggest that VA benefit outreach efforts may gain from
      increased focus on those most vulnerable and most on the outskirts of the VA
      system.

PMID- 17521091
TI  - Civil affairs augmentation of Special Forces units greatly enhance MEDRETE
      impact.
AB  - Medical readiness education and training exercises (MEDRETEs) provide acute,
      primary, and preventative medicine services to populations in countries other
      than the United States. MEDRETEs provide training in deployment, redeployment,
      austere environment medicine, supply, security, and defense for our active duty
      and reserve component personnel. MEDRETEs also improve public relations, advance
      U.S. foreign policy, and build confidence in the partner nation services. This
      article documents the great increase in ability to see multiple patients provided
      when a Special Forces unit is augmented by assistance from Civil Affairs
      attachments.

PMID- 17521092
TI  - The mobile army surgical hospital humanitarian assistance mission in Pakistan:
      the primary care experience.
AB  - Military surgical field hospitals are frequently deployed for humanitarian
      missions. Current Department of Defense doctrine and World Health Organization
      policy question the appropriateness of their use, because the majority of
      patients require nonsurgical care. We describe our experiences during the
      deployment of a mobile army surgical hospital in response to the October 8, 2005,
      earthquake in Pakistan. More than 20,000 patients received care during a 4-month
      period. An initially high surgical workload quickly decreased while the volume of
      primary care patients increased, eventually accounting for 90% of patient visits.
      Our experience supports deploying primary care-oriented units for humanitarian
      missions.

PMID- 17521093
TI  - Evaluation of magnetic resonance imaging regulatory methods in the Israeli Air
      Force.
AB  - BACKGROUND: The use of magnetic resonance (MR) imaging (MRI) among many medical
      professions is growing. Many health care systems have formed control mechanisms
      to ensure proper utilization of MRI. This western world trend is also valid in
      the Israeli Air Force (IAF). At the time of the study, two methods existed for
      consideration of MR requests in the IAF: (1) consideration by a primary reviewer,
      no clinical guidelines (applied to all MR examination requests, knee MR
      excluded). (2) Consideration by a primary reviewer according to basic clinical
      guidelines established by the Israeli Defense Forces medical section and by
      communication with an orthopedic specialist (applied to knee MR requests). Both
      methods did not include consultation with established criteria (such as American
      College of Radiology (ACR) appropriateness criteria). OBJECTIVE: To evaluate the
      appropriateness of the current regulatory methods of MRI utilization in the IAF
      by comparing approval/rejection decisions to established ACR criteria. METHODS:
      The study is a retrospective analysis of written records of air force personnel,
      for whom MRI was requested by a specialist. We gathered information regarding the
      clinical problem and the final decision concerning approval or rejection of the
      MRI request. We then consulted with the ACR appropriateness criteria. In case a
      matching ACR clinical variant was found, an appropriateness value was assigned to
      the request. Otherwise, the request was noted as "ACR irrelevant". We
      predetermined to label all studies with an ACR value of 1 to 3 as inappropriate,
      4 to 6 as "gray zone," and 7 to 9 as appropriate. We then compared the ACR-based
      decision to the original outcome of the request. RESULTS: The overall approval
      rate for MRI requests evaluated by a primary reviewer only was 96%. The overall
      approval rate for MRI requests evaluated by a primary reviewer, basic clinical
      guidelines, and specialist consultation was 51%. Among the four most prevalent MR
      requests types (brain, knee, spine, and shoulder), requests in the 7 to 9 scale
      (appropriate requests) accounted for 52%. Regarding appropriate requests, there
      was a 100% approval rate by a primary reviewer only compared with 17% for
      requests considered by a primary reviewer, basic guidelines, and specialist
      consultation (83% of appropriate requests were rejected by this method). Requests
      in the 1 to 3 scale (inappropriate requests) accounted for 3% of all requests. In
      this group, there was a 100% approval rate by both methods of consideration.
      Requests in the 4 to 6 scale (gray zone requests) also accounted for 3% of the
      total and requests which could not be assigned an ACR appropriateness value (ACR
      irrelevant requests) accounted for 42% of total requests. The rate of approval of
      these requests by a primary reviewer only and by a primary reviewer, guidelines,
      and consultant was 97% and 83%, respectively. CONCLUSIONS: Both MR approval
      mechanisms that were applied in the IAF have not shown a strong correlation with
      ACR appropriateness criteria, with significant rates of both overuse and underuse
      of MRI. The high rate of requests that could not be assigned an ACR
      appropriateness value may indicate a need to broaden the appropriateness criteria
      coverage of clinical conditions and variants.

PMID- 17521094
TI  - The utility of exoantigens for detection of Leishmania infections.
AB  - Exoantigens released by Leishmania promastigotes were the subject of a workshop
      held in Mombasa, Kenya. Investigators from the Walter Reed Army Institute of
      Research (Silver Spring, Maryland) met with scientists from government and
      academic institutes and industry to review the current global status of
      leishmaniasis and to explore the potential role of exoantigens in the detection
      of Leishmania in the vertebrate host and arthropod vector. Some encouraging data,
      particularly in the immunodiagnosis of leishmaniasis, were shared. The
      participants concluded that the meeting provided a unique opportunity for
      investigators working on various aspects of the problem to network and to forge
      productive collaborations that could potentially lead to the development of more
      effective tools to counter this persistent and expanding threat. They recommended
      periodic meetings to assess interval progress, to revise timelines, and to set
      achievable goals. The meeting also highlighted the importance of Leishmania
      infection in the 21st century, with more movement of people from disease-endemic
      to non-disease-endemic countries. Increased incidence and geographic spread of
      leishmaniasis emphasize the need for better and more reliable detection methods.
      Exoantigen-based diagnostic devices hold promise in this direction.

PMID- 17521095
TI  - Modeling hospital response to mild and severe influenza pandemic scenarios under
      normal and expanded capacities.
AB  - William Beaumont Army Medical Center conducted quantitative modeling with
      FluSurge 2.0 (Centers for Disease Control and Prevention) to determine hospital
      capabilities in responding to patient arrival surges of the Fort Bliss population
      in mild 1968-type and severe 1918-type influenza pandemics. Model predictions
      showed that William Beaumont Army Medical Center could adequately care for all
      intensive care unit (ICU) and non-ICU patients during a mild pandemic,
      particularly if hospital capacity was expanded using the emergency management
      plan, excess surge plan, or activation of a contagious disease outbreak facility.
      For a severe influenza pandemic, model predictions showed that hospital beds,
      ventilators, and other resources would be exceeded within 2 or 3 weeks. Even at
      maximal hospital expansion, for a 12-week severe pandemic with a 35% attack rate
      there would be peak demand for 214% of available non-ICU beds, 785% of ICU beds,
      and 392% of ventilators. Health care planners and decision-makers should prepare
      for resource challenges when developing plans for the next influenza pandemic.

PMID- 17521096
TI  - Ocular diseases and nonbattle injuries seen at a tertiary care medical center
      during the Global War on Terrorism.
AB  - We retrospectively reviewed the records of 107 U.S. military personnel referred
      to the Walter Reed Army Medical Center ophthalmology service with eye diseases
      and nonbattle injuries diagnosed during Operation Enduring Freedom and Operation
      Iraqi Freedom. Ocular diseases and nonbattle injuries ranged from minor to vision
      threatening, represented a broad variety of conditions, and required the
      expertise of a number of ophthalmic subspecialists. The most common diagnoses
      were uveitis (13.1%), retinal detachment (11.2%), infectious keratitis (4.7%),
      and choroidal neovascularization (4.7%). Eighty-four patients (78.5%) met Army
      retention standards and were returned to duty. Twenty patients (18.7%) were
      referred to a medical evaluation board, seven (6.5%) of whom failed to meet
      retention standards for eye and vision; the retention status of three patients
      (2.8%) remains to be determined.

PMID- 17521097
TI  - Demographics, stone characteristic, and treatment of urinary calculi at the 47th
      Combat Support Hospital during the first 6 months of Operation Iraqi Freedom.
AB  - There are few publications describing urolithiasis in deployed military
      personnel. Renal colic was the most common urologic indication for air evacuation
      from the 47th Combat Support Hospital during the first 6 months of Operation
      Iraqi Freedom and we describe our observations and experience herein.
      Institutional review board approval was obtained to create a database of patients
      presenting to the 47th Combat Support Hospital with urolithiasis. Patient
      demographics, stone characteristic, imaging modality, urinalysis results,
      treatment course, and outcomes were evaluated for 182 patients. Sixty percent of
      patients qualified for conservative treatment and spontaneous stone passage was
      documented in 28%. We conclude that conservative therapy is safe and appropriate
      initial treatment for the majority of deployed personnel with urinary calculi,
      however, many patients were lost to follow-up. No patient treated conservatively
      required admission for sepsis, azotemia, or other serious stone-related
      complication.

PMID- 17521098
TI  - Practical advance in obtaining an emergency airway via cricothyroidotomy.
AB  - By the time a cricothyroidotomy is deemed necessary, the patient is in critical
      need of an emergency airway before anoxic damage ensues. Two things are necessary
      for the delivery of the requisite oxygen. First, an airway must be rapidly
      established. Second, the airway must be large enough to facilitate ventilation.
      Present methods for emergency cricothyroidotomy include needle cricothyroidotomy,
      which suffers from difficulties in both establishment and ventilation. We
      describe here a practical and widely available method for establishing a timely
      effective airway that has been used successfully for five patients since 1992.

PMID- 17521099
TI  - Utility of ultrasound in the combat theater: experiences of a gynecologist during
      Operation Iraqi Freedom/Operation Enduring Freedom.
AB  - OBJECTIVE: The purpose of this study was to evaluate the utility of ultrasound in
      a combat theater. METHODS: A retrospective review of gynecology visits was
      evaluated at Camp Doha, Kuwait, from August 2003 through April 2004. Of the 1,737
      visits, 237 required pelvic ultrasound. Demographic information, as well as the
      indications, diagnosis, and disposition of the patients, was compiled. RESULTS:
      The average age of the patient requiring ultrasound was 28 +/- 8 years. The
      primary presenting complaint was pelvic pain. Forty percent with pelvic pain had
      no identifiable cause. The most common final diagnosis was pregnancy. Of the 237
      visits, the use of ultrasound resulted in 136 return-to-duty dispositions. Of the
      31% who were administratively redeployed, the majority were secondary to
      pregnancy. CONCLUSION: Gynecologic ultrasound was found to be a very useful tool
      in the combat theater. Ultrasound resulted in improved diagnostic ability and
      enhanced reassurance to both provider and patient.

PMID- 17521100
TI  - Pregnancy during Operation Iraqi Freedom/Operation Enduring Freedom.
AB  - OBJECTIVE: The purpose of this study was to evaluate pregnancy during war-time
      deployment. METHODS: A retrospective review of gynecology visits was evaluated at
      Camp Doha, Kuwait, from August 2003 through April 2004. Of the 1,737 visits, 77
      demonstrated a positive pregnancy test. These charts were evaluated for factors
      that may lead to important information for future deployments. RESULTS: The
      average age of the female soldier with a positive pregnancy test in theater was
      27 +/- 7 years. The primary presenting complaint was amenorrhea. Ninety-two
      percent had an ultrasound. Fifty-four percent of visits were active duty,
      followed by Reserve, National Guard, and civilian government employees. Ninety
      two percent were administratively redeployed. Seventy-seven percent of the
      soldiers became pregnant in country. Twenty-three percent arrived in country
      pregnant. CONCLUSIONS: Given the number of pregnancies before and during
      deployment, current screening procedures as well as new concepts in prevention
      need to be addressed.

PMID- 17521101
TI  - Comparison of home and clinic well-baby visits in a military population.
AB  - Patient satisfaction is an indicator of quality of care received. Home-visit
      programs are associated with increased satisfaction and equivalent clinical
      outcomes but increased cost, compared with clinic visits. We hypothesized that
      home visits for routine well-child care would also be associated with increased
      satisfaction and equivalent outcomes. One thousand infants born at Tripler Army
      Medical Center were identified, and 630 were enrolled. Army and Air Force
      dependents received 2-week clinic visits. Navy and Marine Corps dependents were
      offered home visits. At 4 to 6 weeks, families completed a questionnaire.
      Maternal satisfaction and quality of anticipatory guidance were higher in the
      home-visit group. Clinical outcomes were equal. Home visits for routine well
      child care are valid and are associated with greater maternal satisfaction,
      better anticipatory guidance, and equivalent clinical outcomes.

PMID- 17521102
TI  - Knowledge and attitude of infantry soldiers to hearing conservation.
AB  - OBJECTIVE: This study examined British infantry soldiers' knowledge of hearing
      conservation and explored the various factors that influenced their behavior.
      METHOD: This followed qualitative methodology. Data were collected through focus
      group discussion and semistructured interviews. Twenty-three soldiers from a
      typical infantry unit were involved in this study. Data analysis involved both
      question and content analysis. Validity of the research instrument and
      reliability were ensured. RESULTS: All of the soldiers felt their hearing could
      be affected by their job. Even though many were not aware of the presence of a
      hearing conservation policy, they knew about specific aspects of the policy. A
      number of factors prevented the proper use of the personal hearing protection
      devices even though they were aware of their effectiveness in the reduction of
      noise hazard. These included communication difficulties, discomfort, and the
      impracticability of using them in certain circumstances. There was also a
      suggestion of a preponderance of noise-induced hearing loss on the left, which is
      the side often left unprotected to aid communication. Suggestions were put
      forward on ways of improving the hearing conservation program. CONCLUSION: An
      effective Army hearing conservation program should be comprehensive. It should
      incorporate appropriate knowledge, sociological issues, and economic
      considerations such as choice making and opportunity cost. There should be a well
      structured hearing education program with targeted and appropriate behavioral
      modification. It should be compulsory and include lectures and videos given at
      least once a year. Improvements are required to increase the proper use of
      personal hearing protection devices and thus reduce the morbidity associated with
      noise-induced hearing loss.

PMID- 17521103
TI  - Extracorporeal circulatory systems and their role in military medicine: a
      clinical review.
AB  - This study was undertaken to clinically review the historical use, current
      manufacturing trends, and military application of extracorporeal circulatory
      (ECC) systems to treat pulmonary trauma patients. In the past 50 years, ECC
      support has evolved into a viable treatment option for pulmonary patients. New
      developments in ECC systems, such as heparin-bonded circuit designs like the
      Lifebridge B2T and the Novalung, are giving providers more choices with which to
      initiate ECC support and transport those injured while supporting the global war
      on terrorism. If ECC support is adopted by the military, then a training program
      that includes a review of standard operating procedures, equipment types,
      pharmaceutical dosing, transport with ground and air assets, and the effects of
      temperature and elevation changes on the circuits should be instituted. Reviewing
      all possible treatment choices for pulmonary insults received during this war
      should give providers additional tools with which to save lives.

PMID- 17521104
TI  - Smoking and body weight as markers of fitness for duty among U.S. military
      personnel.
AB  - BACKGROUND: Both tobacco and overweight present serious threats to public health.
      Although the military has targeted both health issues, only weight status is
      included in tests of fitness. This study contrasted the relative utility of body
      weight and smoking as markers for fitness for duty. METHODS: Using data from the
      2002 Department of Defense Survey of Health-Related Behaviors among Military
      Personnel (N = 12,149; 24.7% female), troops were categorized according to weight
      (underweight, healthy weight, overweight, or obese) and smoking status (never
      smoker, former smoker, or current smoker). RESULTS: Logistic models were
      developed to examine the usefulness of smoking status and weight status as
      predictors of items assessing four domains of military fitness for duty, namely,
      physical health, mental health, substance abuse, and legal problems. Smoking
      status was a consistent and strong predictor of items within all four fitness
      domains. In contrast, weight status was not a consistent predictor of fitness.
      CONCLUSION: The military should consider adding smoking status to assessments of
      military fitness. Also, given that underweight and not overweight status
      predicted negative outcomes among military members, the services should consider
      revising their weight status fitness standards.

PMID- 17521105
TI  - U.S. Army Social Work Care Manager Program: an initial program analysis.
AB  - Since the Global War on Terror, the U.S. Army has been transforming to meet
      national security needs. The transformation includes Army mental health programs
      serving soldiers and their families. These programs must be relevant to the needs
      of soldiers and their families and effective at maintaining the force throughout
      the Global War on Terror. The Army Social Work Care Manager Program was initiated
      in July 2003 to enhance mental health support for combat veterans and their
      families. This study provides an initial assessment of this program. A seven-item
      provider questionnaire was administered to 66 care managers (N=66) to obtain an
      initial assessment of their utilization and satisfaction. Findings from 33 (n=33)
      respondents revealed diverse usage across and within installations and modest
      satisfaction with their jobs. Additionally, the biggest challenges care managers
      faced were resourcing and supervision. Recommendations for additional research,
      policy, and practice are provided in this study.

PMID- 17521107
TI  - Illness in a redeployed soldier.
AB  - Overseas deployments place military personnel at risk for tropical diseases not
      typically observed on the U.S. mainland. This case describes the first reported
      case of brucellosis returning from Operation Enduring Freedom and Operation Iraqi
      Freedom. A 31-year-old infantry soldier complained of a 6-week history of
      headaches, relapsing fever, and constitutional symptoms since returning from
      Iraq. This soldier was determined to have the only reported case of brucellosis,
      but was one of many soldiers at risk from eating unpasteurized cheese on the
      local economy. Although malaria and leishmaniasis continue to be the most common
      deployment-related illnesses, brucellosis must also be considered in the
      differential of any redeployed soldier with headache, fever, and body aches.
      Public health as well as command elements must reinforce their role in preventing
      exposure to this pathogen.

PMID- 17521106
TI  - Increased risk of viral hepatitis in Taiwanese male conscriptees with tattoos.
AB  - A number of previous literature reviews and research studies have found a
      correlation between viral hepatitis infections and tattoos. The 1897 subjects of
      the current study were young adult male military recruits in southern Taiwan (476
      with tattoos and 1421 without tattoos) who underwent induction physical
      examinations before conscription. During the examination, blood samples were
      collected to screen for hepatitis B surface antigen, antibodies to hepatitis C
      virus (anti-hepatitis B HCV), syphilis, and human immunodeficiency virus.
      Approximately 25.1% had tattoos, 11.3% were positive for HBV surface antigen,
      2.5% were positive for HCV antibody, and 2.1% were positive for HCV RNA. The odds
      ratios for positive hepatitis B virus and HCV infection status were 1.38 (95%
      confidence interval, 0.98-1.93) and 5.00 (95% confidence interval, 1.83-13.67),
      respectively, for those with tattoos, compared with those with no tattoos. All
      conscriptees were seronegative for syphilis and human immunodeficiency virus.

PMID- 17521108
TI  - Implications of venom hypersensitivity for a deploying soldier.
AB  - Venom immunotherapy (VIT) is a life-saving medical treatment for individuals
      allergic to Hymenoptera species. Delivery of VIT is a complex process that
      requires proper extract preparation, shipping, storage, refrigeration, and
      administration by qualified medical personnel in a facility that can manage a
      life-threatening allergic emergency (anaphylaxis). Successful VIT requires 3 to 5
      years of uninterrupted maintenance injections, which may be difficult to maintain
      during deployments, particularly in combat operations. The complexity of VIT has
      resulted in service members being deemed nondeployable and has led to
      interruption or discontinuation of VIT for deployed service members in the past.
      We report the case of a 34-year-old Army National Guard soldier who successfully
      received maintenance VIT while deployed to Operation Iraqi Freedom. This case
      demonstrates that, with proper coordination and appropriate risk assessment,
      continuation of complex medical care, such as VIT, can be supported in a combat
      zone.

PMID- 17521109
TI  - Endoscopic treatment of pancreatic duct disruption due to blunt abdominal trauma:
      a case report.
AB  - It is very difficult to determine and treat injury of the main pancreatic duct
      and its outcomes secondary to blunt abdominal trauma. In this study, we present a
      21-year-old male patient with percutaneous pancreatic fistula due to blunt
      pancreatic damage. We defined the pancreatic duct disruption along with contrast
      media leakage by means of endoscopic retrograde pancreatography. A pancreatic
      duct stent placed after a nasopancreatic catheter was left for 10 weeks. Closure
      of the fistula along with pancreatic duct improvement without any additional
      morbidity was observed after removal of the stent.

PMID- 17521110
TI  - Suicide prevention program in the Army of Serbia and Montenegro.
AB  - Suicide, as one of the greatest problems of maladjustment to the military
      environment, has been a subject of investigation in the Army of Serbia and
      Montenegro (former Yugoslav Army) for more than six decades. The Suicide
      Prevention Program was implemented in December 2003. The aim of the study was to
      follow-up the application of the Suicide Prevention Program in the Army of Serbia
      and Montenegro and its effect on the suicide rate and to compare its incidence in
      civilians. Results of the program application showed that the number of suicides
      in the Army of Serbia and Montenegro was constantly reducing over the period 2004
      to 2005. For soldiers, it was even four times less than in the civilian male
      population, particularly in the period of adaptation to the military environment.
      Since the Suicide Prevention Program in the Army of Serbia and Montenegro proved
      to be successful in decreasing the suicide number, it should be further improved
      and routinely applied.

PMID- 17521111
TI  - Alcohol withdrawal requiring massive prolonged benzodiazepine infusion.
AB  - The objective of this case report is to describe a patient with prolonged alcohol
      withdrawal requiring massive standing doses of benzodiazepines. The setting is
      the medical intensive care unit of the Tripler Army Medical Center, Honolulu,
      Hawaii. The patient is a 58-year-old alcohol-dependent male presenting with
      mental status changes and agitation following an uncomplicated
      cystoprostatectomy, who ultimately required massive doses of benzodiazepines to
      treat his symptoms effectively. We conclude that symptom-triggered therapy proved
      ineffective in this case due to inability to achieve adequate frequency of
      assessments. Ultimately, a lengthy, high-dose, fixed interval benzodiazepine
      regimen was required. The 5-week period of intensive care illustrated that
      scheduled doses of benzodiazepines may be required and massive and prolonged
      doses are sometimes necessary. Adherence to a slow-weaning protocol understood by
      an interdisciplinary team was critical to this patient's recovery. Additionally,
      toxicity from the high-dose medication was not observed.

PMID- 17521112
TI  - Frostbite in a mountain climber treated with hyperbaric oxygen: case report.
AB  - We describe a case of frostbite to all fingers of a mountain climber, treated
      with hyperbaric oxygen (HBO). All fingers eventually healed to full function,
      with only some cosmetic deformity to the tip of the most severely affected
      finger. Because few cases of frostbite treated with HBO have been reported, we
      hope that such case reports will stimulate future research in this area. It is
      hoped that multiple anecdotal cases may help guide future research in this area.
      Sequential digital photographs were taken at various stages of healing during HBO
      treatments. We raise the possibility of photographic techniques and standards
      that may facilitate planning of therapy for frostbite with improved treatment
      comparisons, resulting in more consistency in the future. For example, a
      graphical software application is described that allows morphing of sequential
      images to demonstrate healing progress in a concise movie format. The morphing
      allows concise demonstration of healing to the referring provider and patient and
      helps in teaching and research on frostbite treatment outcomes.

PMID- 17521113
TI  - "Stonewall" Jackson.

PMID- 17521114
TI  - Answer to last month's radiology case and image: osteoid osteoma.

PMID- 17521115
TI  - Harmonization of nutrient intake values.
AB  - The conceptual framework for the various NIVs is depicted in figure 1 along with
      the methodological approaches and applications. The NIVs consist of two values
      derived from a statistical evaluation of data on nutrient requirements, the
      average nutrient requirement (ANR), or nutrient toxicities, the upper nutrient
      level (UNL). The individual nutrient levelx (INLx) is derived from the
      distribution of average nutrient requirements. The percentile chosen is often
      98%, which is equivalent to 2 SD above the mean requirement. Concepts underlying
      the NIVs include criteria for establishing a nutrient requirement, e.g., ferritin
      stores, nitrogen balance, or serum vitamin C. Once the requirement for the
      absorbed nutrient is determined, it may be necessary to adjust the value for food
      sources, i.e., bioavailability, or host factors, such as the effect of infection
      on nutrient utilization. Other concepts that committees may want to consider when
      establishing NIVs include the effects of genetic variation on nutrient
      requirements and the role of the nutrient in preventing long-term disease. Two
      fundamental uses of NIVs are for assessing the adequacy of nutrient intakes and
      for planning diets for individuals and populations. Establishing the NIV using
      the statistical framework proposed in this report improves the efficacy of the
      values for identifying risks of nutrient deficiency or excess among individuals
      and populations. NIVs also are applied to a number of aspects of food and
      nutrition policy. Some examples include regulatory issues and trade, labeling,
      planning programs for alleviating public health nutrition problems, food
      fortification, and dietary guidance.

PMID- 17521116
TI  - Nutrient intake values (NIVs): a recommended terminology and framework for the
      derivation of values.
AB  - Although most countries and regions around the world set recommended nutrient
      intake values for their populations, there is no standardized terminology or
      framework for establishing these standards. Different terms used for various
      components of a set of dietary standards are described in this paper and a common
      set of terminology is proposed. The recommended terminology suggests that the set
      of values be called nutrient intake values (NIVs) and that the set be composed of
      three different values. The average nutrient requirement (ANR) reflects the
      median requirement for a nutrient in a specific population. The individual
      nutrient level (INLx) is the recommended level of nutrient intake for all healthy
      people in the population, which is set at a certain level x above the mean
      requirement. For example, a value set at 2 standard deviations above the mean
      requirement would cover the needs of 98% of the population and would be INL98.
      The third component of the NIVs is an upper nutrient level (UNL), which is the
      highest level of daily nutrient intake that is likely to pose no risk of adverse
      health effects for almost all individuals in a specified life-stage group. The
      proposed framework for deriving a set of NIVs is based on a statistical approach
      for determining the midpoint of a distribution of requirements for a set of
      nutrients in a population (the ANR), the standard deviation of the requirements,
      and an individual nutrient level that assures health at some point above the
      mean, e.g., 2 standard deviations. Ideally, a second set of distributions of risk
      of excessive intakes is used as the basis for a UNL.

PMID- 17521117
TI  - Nutrient risk assessment: setting upper levels and an opportunity for
      harmonization.
AB  - Upper levels are estimates of the quantity of a nutrient that can be ingested
      daily over a lifetime without appreciable risk to health. The approach to
      establishing upper levels for nutrients, nutrient risk assessment, has derived
      from the risk assessment of foreign chemicals that are deliberately added to
      foods, or are in food as contaminants. This process of risk assessment is
      rigorous and transparent, particularly in dealing with the uncertainty arising
      from the data available and their assessment and extrapolation to human
      populations. Hazard identification and characterization, i.e., a dose-response
      pattern, as applied to xenobiotics, are discussed first, and then the
      difficulties of applying this approach to nutrients are reviewed. Nutrients, in
      contrast to foreign chemicals, have specific and selective metabolic pathways and
      homeostasis, as well as specific functions. This is the source of differences in
      the nutrient risk assessments produced by various national and international
      advisory bodies. Although the same data are used in such exercises, different
      judgments are made about identifying adverse effects, the nature of uncertainties
      in the assessment, and in matching the upper levels with exposure assessments and
      dietary reference values. The establishment of different upper levels for
      different national and international communities is a source of confusion in
      public health policy and practice and a barrier to trade. It is proposed that a
      basis for harmonizing the existing approaches used in nutrient risk assessment
      would be the collaborative development of the model for establishing upper levels
      of intake for nutrients and related substances that has been recently described
      by a Joint Task Force of the World Health Organization and the Food and
      Agriculture Organization.

PMID- 17521118
TI  - Using criteria to establish nutrient intake values (NIVs).
AB  - One of the most important of the nutrient intake values (NIVs) is the average
      nutrient requirement (ANR). The ANR is defined as an intake value that will be
      adequate for half of the individuals in a group of people with similar
      characteristics. It is used to estimate the prevalence of adequacy, and it serves
      as the basis for the individual nutrient level (INLx). The determination of
      adequacy is a complex process, with the resulting value of the ANR dependent on
      the criterion or functional outcome chosen to define nutrient adequacy. Because
      nutrients have multiple sites of action in human metabolism, it is possible to
      demonstrate abnormal function in one parameter measured or observed as a result
      of inadequate intake of a nutrient, while other parameters requiring the same
      nutrient appear normal or within normal ranges. Thus, depending on the criterion
      of adequacy selected, the requirement for a given nutrient may be at a lower or a
      higher intake amount. In harmonizing development of NIVs, it is important to
      clearly identify the criterion of adequacy selected and the rationale for its
      selection. Rarely are available data sufficient to provide dose-response
      information from which to select a level of intake at which half of the
      individuals demonstrate adequacy and half appear to demonstrate inadequacy. Three
      levels of intake, of which at least one level of intake is below the requirement
      for most of the individuals in the sample, and one level of intake is above their
      requirement, are useful for establishing a level at which half of the group might
      be considered to demonstrate adequacy. Types of human nutrient studies that may
      be used to obtain data are discussed, as well as characteristics of the sample
      size needed to demonstrate adequacy. The variation in requirements is also an
      important aspect in predicting levels of intake that will have defined
      probabilities of adequacy for groups (to develop the INLx where x is the defined
      probability chosen). An analysis of the origins of different types of variability
      is presented. When estimating energy requirements, a special case of NIVs,
      important issues must be considered. Additionally, an example of evaluating data
      used to establish an ANR for vitamin A, and the effect of variability in
      requirements for vitamin A, is provided.

PMID- 17521119
TI  - Methods for using nutrient intake values (NIVs) to assess or plan nutrient
      intakes.
AB  - This article describes the methods for using nutrient intake values (NIVs) to
      plan and assess intakes of both individuals and population groups. The advantages
      of the more recent standards, which use an average nutrient requirement (ANR) and
      its standard deviation to describe the distribution of nutrient requirements, are
      highlighted. The goal of assessing the intake of an individual is to determine
      the probability that the person's usual diet is meeting his or her nutrient needs
      and whether the person is at risk for adverse effects from excessive intakes,
      whereas the goal of planning an individual's intake is to ensure that the
      probability of inadequate intake and the likelihood of excessive intake are both
      small. The goal of assessing intakes of groups is to determine the prevalence of
      inadequate intakes and the prevalence of potentially excessive intakes, whereas
      the goal of planning nutrient intakes for groups is to minimize the prevalence of
      inadequate intakes and also to minimize the prevalence of potentially excessive
      intakes. For all of these goals, it is important to utilize appropriate food
      composition tables and accurate dietary assessment methods. To fully utilize the
      new paradigm, it will be necessary for the professional nutrition community to
      identify ways to implement these new procedures in nutrition research and
      nutrition programs, to describe the strengths and weaknesses of the results, and
      to contribute to the evolution of both the theory and the application of the NIVs
      when planning and assessing diets.

PMID- 17521120
TI  - Determining life-stage groups and extrapolating nutrient intake values (NIVs).
AB  - The derivation of reference values in 11 current dietary reference standards is
      often based on methods of extrapolation or interpolation, but these are not
      consistent across reports. Such methods are frequently employed to derive
      nutrient intake values (NIVs) for infants and children owing to the paucity of
      relevant research data available. The most common method is to extrapolate values
      for children down from those of adults, employing a weight or metabolic factor
      and adjusting for growth. In some instances, values for young children are
      extrapolated up from infants, values for adults are extrapolated up from
      children, or values for older adults are extrapolated up from young adults.
      Extrapolation is employed to estimate not only nutrient requirement or adequate
      intake but also the upper tolerable levels of intake. Extrapolation methods may
      also form the basis of estimates of tissue deposition of nutrients during growth
      in children and for the maternal/fetal dyad in pregnancy with adjustments for
      metabolic efficiency. Likewise, recommended intakes during lactation are
      extrapolated from known secretion of the nutrient in milk with adjustments for
      bioavailability. For future dietary standards, a first priority is to obtain
      relevant scientific data using current methodology, such as stable isotope
      tracers, body composition analysis, and appropriate biomarkers, from which NIVs
      for each age group can be derived. Extrapolation to derive an NIV is only
      acceptable in the sheer absence of sound scientific data and must be modeled with
      a consistent approach. For the purpose of harmonization of dietary standards, we
      recommend the following approaches that should be clearly described in reports:
      standardization of age groups on a biological basis (growth and pubertal stages)
      with consideration of relevant developmental milestones throughout childhood;
      application of internationally accepted standards for growth, body size, body
      composition, fetal and maternal nutrient accretion in pregnancy, and milk
      composition; and inclusion of appropriate adjustments (metabolic efficiency,
      weight change, or physical activity).

PMID- 17521121
TI  - The role of diet- and host-related factors in nutrient bioavailability and thus
      in nutrient-based dietary requirement estimates.
AB  - To convert physiological requirements into dietary requirements, adjustments are
      needed for some nutrients that take into account certain diet- and host-related
      factors specific to a country or region. Nutrients whose requirements should be
      adjusted in this way include calcium, magnesium, iron, zinc, protein, folate,
      vitamin A, and carotenoids. The diet-related factors that must be considered
      depend on the nature of the habitual diet and may include the chemical form of
      the nutrient and the nature of the dietary matrix, interactions between nutrients
      and/or organic components, and food preparation and processing practices within
      the country or region. The host-related factors can be further subdivided into
      intestinal and systemic factors. Reductions in the secretion of hydrochloric
      acid, gastric acid, and/or intrinsic factor, together with alterations in the
      permeability of the intestinal mucosa, are all examples of intestinal factors
      that can markedly influence the absorption of certain nutrients, but that are
      often ignored when setting dietary requirements. Systemic factors that should
      also be considered include nutrient status of the host, age, sex, ethnicity,
      genotype, and physiological state (e.g., pregnancy or lactation), and chronic and
      acute infectious disease states. Algorithms can estimate the bioavailability of
      iron, zinc, protein, folate, vitamin A, and carotenoids, although their accuracy
      is limited by the complex interactions among the absorption modifiers in the
      whole diet. For calcium and magnesium, the amount available for absorption is
      still estimated from their major food sources in the habitual diet. Currently,
      there are often large differences in the adjustments employed to convert
      physiological requirements to dietary requirements, even among countries
      consuming diets of similar patterns.

PMID- 17521122
TI  - Human nutrition and genetic variation.
AB  - Human genetic variation is a determinant of nutrient efficacy and of tolerances
      and intolerances and has the potential to influence nutrient intake values
      (NIVs). Knowledge derived from the comprehensive identification of human genetic
      variation offers the potential to predict the physiological and pathological
      consequences of individual genetic differences and prevent and/or manage adverse
      outcomes through diet. Nutrients and genomes interact reciprocally; genomes
      confer differences in nutrient utilization, whereas nutrients effectively modify
      genome expression, stability, and viability. Understanding the interactions that
      occur among human genes, including all genetic variants thereof, and
      environmental exposures is enabling the development of genotype-specific
      nutritional regimens that prevent disease and promote wellness for individuals
      and populations throughout the life cycle. Genomic technologies may provide new
      criteria for establishing NIVs. The impact of a gene variant on NIVs will be
      dependent on its penetrance and prevalence within a population. Recent
      experiences indicate that few gene variants are anticipated to be sufficiently
      penetrant to affect average requirement (AR) values to a greater degree than
      environmental factors. If highly penetrant gene variants are identified that
      affect nutrient requirements, the prevalence of the variant in that country or
      region will determine the feasibility and necessity of deriving more than one AR
      or upper limit (UL) for affected genetic subgroups.

PMID- 17521123
TI  - Application of nutrient intake values (NIVs).
AB  - The process of applying nutrient intake values (NIVs) for dietary assessment,
      planning, and implementing programs is discussed in this paper. In addition to
      assessing, monitoring, and evaluating nutritional situations, applications
      include planning food policies, strategies, and programs for promotion of optimal
      nutrition and preventing and treating malnutrition (both over- and
      undernutrition). Other applications include nutrition education, food and
      nutrient legislation, marketing and labeling, research, product development, food
      procurement and trade (import and export), food aid, and therapeutic (clinical)
      nutrition. Specific examples of how NIVs are used to develop food labels,
      fortification policies, and food-based dietary guidelines are described.
      Applications in both developed and developing countries are also described. In
      summary, NIVs are the scientific backbone of all aspects of nutrition policy in
      countries and regions worldwide.

PMID- 17521124
TI  - Trade, development, and regulatory issues in food.
AB  - Trade in food and animal products has increased several-fold in the past decade,
      and simultaneously regulations governing the movement of such products across
      national boundaries have also increased. The present study reviews harmonization
      in food trade regulation by focusing on nutritional aspects to understand its
      role in enhancing world trade on the one hand and consumer interest and welfare
      on the other. Harmonization to a large extent brings in more regulation from the
      developed world acting through their governments, consumer organizations, and
      multinational companies; it does not seem to address, in general, the concerns of
      the large segments of the poor population for whom agriculture and food trade are
      the main sources of livelihood. There is a lack of quantifiable estimates of the
      loss in well-being of the disadvantaged. However, there is substantial research
      focused on the potential harm to developed nations as a result of nonadherence to
      the rules. Clearly, lack of adequate infrastructure, resource constraints, and
      weak institutions not only result in poor food safety regulation within
      developing countries but also remain barriers to realizing the greater potential
      benefits from increased trade. Harmonization of standards would have some losers
      and some winners, but to make it more inclusive, scientific knowledge alone may
      not be adequate; social and cultural aspects also need to be considered, since
      food systems differ among regions, with varying preferences, local resource
      availability, and levels of economic development. Improvement in governance in
      many countries not only would ensure better participation in international rule
      making and the negotiation process for fairer trade but also would result in
      effective domestic legislation to ensure safer health for citizens, resulting in
      higher overall well-being.

PMID- 17521125
TI  - Beyond recommendations: implementing food-based dietary guidelines for healthier
      populations.
AB  - To reduce the increased burden of diet-related disease and promote human
      potential through food and nutrition globally, harmonization of efforts is
      urgently needed. This article examines the concept of food-based dietary
      guidelines (FBDGs) and discusses the possibilities and challenges of harmonizing
      the process of developing and implementing dietary guidelines. The authors argue
      that while the development of FBDGs has contributed to the understanding of the
      role of nutrients and foods in achieving optimal health, the impact of these
      guidelines on human health has been limited. Science or evidence must be used in
      FBDG development; nevertheless, there are limitations in current nutrition
      science. FBDGs should address the health consequences of dietary insufficiency,
      excess, or imbalance with a broader perspective, considering the totality of the
      effects of a given dietary pattern, rather than focusing on single nutrients
      alone. Moreover, the food selection guideline should be seen as complementary to
      a strategic, comprehensive, and culturally appropriate dietary and health
      promoting intervention, and not only as a tool for providing nutrition policy and
      information. Technically, a single unified global set of FBDGs may be desirable
      and even achievable. This concept, however, presents novel challenges on how to
      address cultural diversity and the complex social, economic, and political
      interactions between humans and the food supply, not to mention the complexity of
      its communication and implementation. Therefore, global harmonized efforts in
      support of strategic dietary interventions, together with strong global
      scientific support and facilitation for the development and communication of
      FBDGs at national or regional levels, are proposed to implement FBDGs for
      healthier populations.

PMID- 17521126
TI  - Characterization of polycyclic aromatic hydrocarbon bioavailability in estuarine
      sediments using thin-film extraction.
AB  - It is well documented that the bioavailability of hydrophobic organic chemicals
      (HOCs) can vary substantially among sediments. This makes risk assessments based
      on total sediment concentrations problematic. The present study investigates the
      application of thin-film solid-phase extraction to measure bioavailable
      concentrations of phenanthrene in estuarine sediment by comparing concentrations
      of phenanthrene in the amphipod Corophium colo and in thin ethylene/vinyl acetate
      films at different concentrations in three geochemically different sediments. For
      all sediment types, concentrations of phenanthrene in sediments and thin films
      followed linear relationships, indicating first-order exchange kinetics.
      Organism/thin-film concentration ratios did not vary systematically among
      sediment types but dropped significantly with increasing phenanthrene
      concentration in the sediments. While at low phenanthrene concentrations in the
      sediment fugacities of phenanthrene in the amphipods approached the fugacities in
      the thin films, they were significantly lower than those in the sediments at
      higher concentrations. While phenanthrene concentrations in the three sediment
      types were identical, biota sediment accumulation factors and concentrations in
      amphipods and thin films were consistently lower in sediments enriched with black
      carbon than in sediments with sedimentary organic matter bearing a more
      diagenetic organic signature. It is concluded that, for the range of
      concentrations tested, thin-film solid-phase extraction can be a useful tool in
      the characterization of differences in bioavailability of HOCs among sediment
      types.

PMID- 17521127
TI  - Biomagnification and polychlorinated biphenyl congener distribution in an aquatic
      predator-prey, host-parasite system.
AB  - Biomagnification and polychlorinated biphenyl (PCB) congener distribution was
      examined in a predator-prey, host-parasite system, in which Atlantic salmon
      (Salmo salar) preyed upon sprat (Sprattus sprattus). Eubothrium crassum was an
      intestinal parasite in salmon that also "preyed upon" sprat, because the
      parasites gained access to foodstuffs via the host (salmon) gut. Salmon contained
      significantly higher concentrations of total PCBs compared to both parasites and
      prey (sprat), but no difference in PCB concentration was found between sprat and
      E. crassum. Salmon biomagnified several PCB congeners from their diet (sprat),
      whereas parasites did not, despite the fact that both salmon and their parasites
      ingested the same prey. Differences in nutrient uptake mechanisms between the
      host and their parasites, in addition to the lack of a gastrointestinal tract in
      the cestode, may explain the lack of biomagnification in E. crassum. No
      difference was found in PCB congener distribution between parasites, salmon, and
      sprat, and none of the animal types showed a preference for accumulating more or
      less lipophilic congeners (congeners with a high or low octanol/water partition
      coefficient [K(ow)]). Biomagnification factors for individual congeners in salmon
      did not increase with K(ow); rather, they were constant, as shown by a linear
      relationship for congener concentration in prey and predator.

PMID- 17521128
TI  - Mineralization of atrazine in agricultural soil: inhibition by nitrogen.
AB  - Microbial mineralization of atrazine was characterized in soils and liquid media
      in the presence of nitrogen fertilizer concentrations representing typical field
      applications. The mineralization of atrazine in soils varied between 6 and 99%
      after 18 d of incubation. Half-lives of between 0.99 and more than 18 d were
      obtained. Mineralization kinetics and degree are related by a reciprocal trend to
      concentrations of available nitrogen in the soil. In liquid media, half-lives
      were calculated as 0.12 d in the absence of fertilizer nitrogen and as 79 d in
      the presence of 1,000 mg/L of KNO3-N. Only 20% of atrazine was mineralized after
      18 d of incubation in the presence of this concentration of KNO3-N, whereas
      greater than 90% mineralization occurred after 2 d of incubation in liquid medium
      without KNO3-N. The results demonstrate that the mineralization of atrazine is
      inhibited even at fertilizer nitrogen levels lower than typical field
      applications. Inhibition in soil is lower than that in liquid medium, possibly
      because of the higher complexity of the soil system. This may explain why
      atrazine that infiltrates to the groundwater is persistent. The microbial
      consortium of the soils was characterized, and seven species were identified. The
      degrading capacity of these species suggests that only three species are involved
      in the degradation of atrazine.

PMID- 17521129
TI  - Polychlorinated biphenyls, DDT, polybrominated diphenyl ethers, and organic
      pesticides in United Kingdom harbor seals (Phoca vitulina)--mixed exposures and
      thyroid homeostasis.
AB  - Polychlorinated biphenyls, DDT and its metabolites, polybrominated diphenyl
      ethers, and selected organochlorine pesticide concentrations were measured in
      blubber samples from 60 free-living harbor seals in 2003 from five sites around
      the United Kingdom coast. Significant regional differences among contaminant
      levels were found, with seals on Islay and Jura (southwest Scotland) having the
      highest levels of polychlorinated biphenyls and seals in the Wash (eastern
      England) having the highest polybrominated diphenyl ether levels. Animals from
      the north and northeast of Scotland (Orkney and the Moray Firth) had the lowest
      levels of all the contaminant groups studied. Congener-specific profiles of
      polychlorinated biphenyls and polybrominated diphenyl ethers showed relatively
      higher levels of the lower chlorinated and brominated compounds at the more
      northerly sites, with the lowest total levels of both chemical groups.
      Significant positive relationships between blubber contaminants and total
      triiodothyronine (TT3) concentrations were found after controlling for the
      potential effects of confounding because of sex, mass, and season. Increased
      serum TT3 levels were significantly related to higher blubber contaminant
      concentrations in the following order: sum of all contaminants > polybrominated
      diphenyl ethers > polychlorinated biphenyls > DDT. Serum TT3 levels in the harbor
      seals with the highest exposures might be indicative of a T3 thyrotoxicosis, but
      without information on free T3 and circulating thyroid-stimulating hormone
      levels, it is difficult to determine the importance of this observation for the
      health of the individuals or populations. However, the mixture of contaminants to
      which United Kingdom harbor seals are exposed has changed over the last few
      decades, and the toxicological and epidemiological importance of adding the
      brominated compounds to the classical organochlorine and heavy metal mixture is
      not known.

PMID- 17521130
TI  - Biodegradability relationships among propylene glycol substances in the
      Organization for Economic Cooperation and Development ready- and seawater
      biodegradability tests.
AB  - Eight propylene glycol substances, ranging from 1,2-propanediol to a
      poly(propylene glycol) (PPG) having number-average molecular weight (M(n)) of
      2,700 (i.e., PPG 2700), were evaluated in the Organization for Economic
      Cooperation and Development (OECD) ready- and seawater biodegradability tests.
      Uniformity in test parameters, such as inoculum source/density and test substance
      concentrations, combined with frequent measurements of O2 consumption and CO2
      evolution, revealed unexpected biodegradability trends across this family of
      substances. Biodegradability in both tests decreased with increased number of oxy
      propylene repeating units (n = 1, 2, 3, 4) of the oligomeric propylene glycols
      (PGs). However, this trend was reversed for the PPG polymers, and increased
      biodegradability was observed with increases of average n to seven, 17, and 34
      (M(n) = 425, 1,000, and 2,000, respectively). This relationship between molecular
      weight and biodegradability was reversed again when average n was incremented
      from 34 (PPG 2000) to 46 (PPG 2700). Six of the tested substances (n = 1, 2, 3,
      7, 17, and 34) met the OECD-specified criteria for "ready biodegradability,"
      whereas the tetrapropylene glycol (n = 4) and PPG 2700 substances failed to meet
      these criteria. Biodegradation half-lives for these eight substances ranged from
      3.8 d (PPG 2000) to 33.2 d (PPG 2700) in the ready test, and from 13.6 (PG) to
      410 d (PPG 2700) in seawater. Biodegradation half-lives in seawater were
      significantly correlated with half-lives determined in the ready test. However,
      half-lives in both tests were correlated poorly with molecular weight, water
      solubility, and log K(ow). It is speculated that the molecular conformation of
      these substances, perhaps more so than these other physicochemical properties,
      has an important role in influencing biodegradability of the propylene glycol
      substances.

PMID- 17521131
TI  - Histidine-rich glycoprotein from the hemolymph of the marine mussel Mytilus
      edulis L. binds Class A, Class B, and borderline metals.
AB  - Few studies have directly addressed the question of how metals (both essential
      and nonessential) are transported in the circulatory system of bivalve mollusks.
      One potential metal-transport protein, histidine-rich glycoprotein (HRG), has
      previously been isolated and characterized from the blood plasma of the marine
      mussel Mytilus edulis L. The present study was undertaken to investigate the
      extent to which mussel HRG can bind a variety of essential and nonessential
      metals in vitro, using immobilized metal-ion affinity chromatography (IMAC) and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The equilibrium metal
      speciation model MINTEQA2 was used to compute the amount of metal that bound to
      the IMAC packing material during the charging and initial wash steps. Results
      demonstrated that HRG can bind all seven of the metals tested (Ca, Cd, Hg, Mg,
      Ni, Pd, and Zn) and that HRG is the only metal-binding protein in IMAC eluents.
      Because HRG-metal binding strengths (log K(a)) likely correspond with histidine
      metal binding strengths, and because HRG is the predominant mussel plasma
      protein, the majority of each of the seven metals probably would be present in
      mussel blood as protein-bound metal rather than as free metal ion. The finding
      that a single mussel plasma protein may be responsible for binding all these
      metals raises important questions about how these different metals are
      subsequently transferred from HRG to different tissues of the mussel, where they
      may exhibit tissue-specific patterns of utilization, sequestration, elimination,
      and toxicity.

PMID- 17521132
TI  - Bioavailability of polycyclic aromatic hydrocarbons sequestered in sediment:
      microbial study and model prediction.
AB  - In field studies and remediation projects, contaminants persist in soil and
      sediment much longer than would be estimated based on contaminant physical and
      chemical properties; such observations indicate that a fraction of contaminants
      in soil/sediment is much less available to the degrading microorganisms or
      chemical reagents. Many researchers attribute this reduced availability/
      bioavailability to the sequestration (also referred to as resistant desorption or
      desorption hysteresis) of contaminants in soil/sediment. In the present research,
      desorption and bioavailability of naphthalene, phenanthrene, and fluoranthene
      were studied to evaluate the impact of sequestration on the biodegradability of
      these three polycyclic aromatic hydrocarbons (PAHs). Experimental results
      indicate that only desorbed PAHs are bioavailable and that the bioavailability of
      sequestered PAHs could be well predicted with a modified bioavailability model,
      which uses a biphasic desorption model to replace the conventional
      adsorption/desorption model. Findings in the present study might have important
      implications for site remediation: After the initial stage of remediation (i.e.,
      after the readily desorbable fraction of contaminants is removed from
      soil/sediment), desorption of sequestered contaminants becomes the rate-limiting
      step of remediation. In this stage, the availability of contaminants is so low
      that even aggressive remediation would have little effect on overall mass
      reduction. Thus, a more cost-effective approach for site remediation might
      consist of an initial aggressive treatment followed by plume control, such as
      monitored natural attenuation.

PMID- 17521133
TI  - Aerobic degradation and photolysis of tylosin in water and soil.
AB  - Veterinary antibiotics enter the environment through the application of organic
      fertilizers to cropland. In this study, the aerobic degradation of tylosin, a
      widely used antibiotic in the production of livestock and poultry, was conducted
      in water and in soil in an effort to further investigate its environmental fate.
      Tylosin is a macrolide antibiotic, which consists of four factors (A, B, C, D).
      Water and soil were sampled at selected times and analyzed for tylosin and its
      degradation products by high-performance liquid chromatography (HPLC), with
      product identification confirmed by HPLC-mass spectrometry. Tylosin A is degraded
      with a half-life of 200 d in the light in water, and the total loss of tylosin A
      in the dark is 6% of the initial spiked amount during the experimental period.
      Tylosin C and D are relatively stable except in ultrapure water in the light.
      Slight increases of tylosin B after two months and formation of two photoreaction
      isomers of tylosin A were observed under exposure to light. However, tylosin
      probably would degrade faster if the experimental containers did not prevent
      ultraviolet transmission. In soil, tylosin A has a dissipation half-life of 7 d,
      and tylosin D is slightly more stable, with a dissipation half-life of 8 d in
      unsterilized and sterilized soil. Sorption and abiotic degradation are the major
      factors influencing the loss of tylosin in the environment, and no biotic
      degradation was observed at the test concentration either in pond water or in an
      agronomic soil, as determined by comparing dissipation profiles in sterilized and
      unsterilized conditions.

PMID- 17521134
TI  - Soil biogeochemical toxicity end points for sub-Antarctic islands contaminated
      with petroleum hydrocarbons.
AB  - Sub-Antarctic islands have been subjected to petroleum hydrocarbon spills, yet no
      information is available regarding the toxicity of petroleum hydrocarbons to
      these subpolar soils. The purpose of the present study was to identify soil
      biogeochemical toxicity end points for petroleum hydrocarbon contamination in sub
      Antarctic soil. Soil from Macquarie Island, a sub-Antarctic island south of
      Australia, was collected and exposed to 10 concentrations of Special Antarctic
      Blend (SAB) diesel fuel, ranging from 0 to 50,000 mg fuel/kg soil, for a 21-d
      period. The sensitivity of nitrification, denitrification, carbohydrate
      utilization, and total soil respiration to SAB fuel was assessed. Potential
      nitrification activity was the most sensitive indicator of SAB contamination
      assessed for nitrogen cycling, with an IC20 (concentration that results in a 20%
      change from the control response) of 190 mg fuel/ kg soil. Potential
      denitrification activity was not as sensitive to SAB contamination, with an IC20
      of 950 mg fuel/kg soil for nitrous oxide production. Nitrous oxide consumption
      was unaffected by SAB contamination. Carbohydrate utilization (respiration caused
      by sucrose) was a more sensitive indicator (IC20, 16 mg fuel/kg soil) of SAB
      contamination than total respiration (IC20, 220 mg fuel/kg soil). However, total
      soil respiration was a more responsive measurement end point, increasing soil
      respiration over a 72-h period by 17 mg of CO2, compared to a change of only 2.1
      mg of CO2 for carbohydrate utilization. Our results indicate that IC20s varied
      between 16 to 950 mg fuel/kg soil for Macquarie Island soil spiked with SAB
      diesel fuel. These results indicate that current cleanup levels derived from
      temperate zones may be too liberal for soil contamination in sub-Antarctic
      islands.

PMID- 17521136
TI  - Dose verification after topical treatment of alligator (Alligator
      mississippiensis) eggs.
AB  - Numerous studies have used temperature-dependent sex determination in reptilian
      eggs to investigate potential developmental effects of exogenously applied
      substances. However, few studies have measured the dose carried across the
      eggshell. We report embryonic mortality and internal egg concentrations
      determined by gas chromatography-mass spectrometry two weeks after exposure of
      American alligator (Alligator mississippiensis) eggs to chlorinated organic
      pesticides via injection or topical application. Puncturing the eggshell for
      injection produced high mortality compared with unpunctured controls; therefore,
      further evaluation of this method was abandoned. Although higher than controls,
      mortality was much lower in eggs treated topically than in those injected.
      Transfer of chemicals across the eggshell was very low, highly variable, and did
      not correlate with the applied dose after topical application. These results are
      consistent with previous reports in the literature, casting doubt on whether a
      reproducible internal dose can be achieved in reptilian eggs by topical
      treatment.

PMID- 17521135
TI  - Biomonitoring of estrogenic exposure and identification of responsible compounds
      in bream from Dutch surface waters.
AB  - The exposure to and effects of estrogenic compounds in male breams from Dutch
      freshwater locations were investigated. Ovotestis was observed infrequently
      (maximum frequency 16%). However, plasma vitellogenin (VTG) concentration was
      elevated highly at some locations. Estrogenic activities in male bream plasma,
      liver, and in gastrointestinal content were measured in the estrogen-responsive
      chemical-activated luciferase gene expression (ER-CALUX) assay. Plasma
      concentrations of vitellogenin correlated very well with the estrogenic
      activities in gastrointestinal content. The ER-CALUX activity in gastrointestinal
      content thus could provide a biomarker for recent exposure to estrogenic
      compounds, and the gastrointestinal content was chosen as investigative matrix
      for the toxicity identification and evaluation ([TIE]; bioassay-directed
      fractionation) of estrogenic compounds in bream. The approach consisted of a
      reversed-phase high-performance liquid chromatography fractionation of
      gastrointestinal content extract, directed by ER-CALUX and followed by gas
      chromatography analysis. The estrogenic hormones 17beta-estradiol and its
      metabolite estrone were identified as major contributors to the activity at all
      locations (except the reference location), independent of the presence or absence
      of a known source of estrogenic activity, such as a sewage treatment plant.
      Chemical screening showed the presence of other pollutants, such as a lower
      chlorinated dioxin and the disinfectants clorophene and triclosan. However, these
      compounds did not have high estrogenic potencies and their concentrations were
      not high enough to contribute significantly to the observed estrogenic activity.

PMID- 17521137
TI  - Topical dose delivery in the reptilian egg treatment model.
AB  - Developing assays to detect endocrine-mediated toxicity from in ovo or in utero
      exposure is a current challenge in regulatory toxicology. Some species of
      reptiles exhibiting a unique mode of sex determination, in which the incubation
      temperature during a critical period determines gonadal sex, have been explored
      as an in ovo model to screen environmental contaminants for endocrine effects. We
      critically review published egg-exposure studies and conclude that data regarding
      the pharmacokinetics of topically applied substances are insufficient to validate
      dose-response relationships for the effects of chemicals on in ovo endocrine
      function or gender determination in reptiles. The insufficiencies in these data
      largely result from methodological failures, including lack of measurement
      verification, failure to investigate and control extraneous factors affecting the
      measurements, and lack of independent replication of results. Considerable
      additional research will be necessary to alleviate these methodological
      inadequacies. Given the current status of the data, topical treatment of
      reptilian eggs cannot be considered to be a valid means of establishing causal
      relationships between chemical treatment and biological outcome.

PMID- 17521138
TI  - In vivo assessment of the capacity of androstenedione to masculinize female
      mosquitofish (Gambusia affinis) exposed through dietary and static renewal
      methods.
AB  - In this study, we investigated the capacity of androstenedione to masculinize
      female mosquitofish. Previous studies have identified androstenedione in the
      water and sediment of the Fenholloway River, a Florida, USA, coastal river that
      receives paper mill effluent and contains masculinized eastern mosquitofish
      (Gambusia holbrooki). Females of the closely related western mosquitofish,
      Gambusia affinis, were exposed to androstenedione through both dietary and static
      renewal treatments. Morphological masculinization of female mosquitofish is
      characterized by the development of a male secondary sexual trait: an elongated
      and modified anal fin (gonopodium). Dietary exposure to 0.7, 7, 70, and 700
      microg of androstenedione per gram of food failed to induce gonopodial
      development at any concentration within the six-week exposure period. Static
      renewal treatments used androstenedione concentrations of 0.14, 1.4, 14, 140, and
      350 nM. Significant anal fin ray elongation was observed in all but the lowest
      exposure group. Fish growth during the static renewal exposure experiment was
      negatively correlated with androstenedione concentration. No significant effects
      were observed for gonadosomatic index, vitellogenin expression, or ovarian area
      in fish exposed to androstenedione via either the dietary or static renewal
      methods. These results indicate that exposure to androstenedione via water can
      cause masculinization of adult female mosquitofish in a relatively short period
      of time and that acute dietary exposure to androstenedione at the concentrations
      used is not sufficient to induce masculinization.

PMID- 17521139
TI  - Influence of seasonality and exposure on the accumulation and reproductive
      effects of p,p'-dichlorodiphenyldichloroethane and dieldrin in largemouth bass.
AB  - Two studies investigated the accumulation and reproductive effects of p,p'
      dichlorodiphenyldichloroethane (DDE) and dieldrin over 30 or 120 d of oral
      exposure in captive Florida, USA, largemouth bass (Micropterus salmoides
      floridanus). The 30-d exposures were conducted during the peak reproductive
      season, and the 120-d study was conducted to simulate exposure throughout the
      ovarian cycle. Whole body chemical residue concentrations were similar,
      regardless of exposure duration, for the medium and high feed concentrations of
      either chemical; however, the low-dose residue concentrations were much lower,
      yet similar to natural exposures. No clear dose-response relationships were
      identified between chemical dose and morphological (length, weight, hepatosomatic
      index) or reproductive endpoints (sex steroid concentration, gonadosomatic index,
      percentage of fry hatching). Reproductive parameters were variable within
      treatment groups, indicating that circulating sex steroids and percent hatch
      endpoints have high natural variability among fish of the same age and
      reproductive stage. However, in general there was a decrease in plasma estradiol
      and 11-ketotestosterone for female and male fish, respectively, that were exposed
      to dieldrin. Overall, results suggest that exposure throughout ovarian
      (follicular) development to either DDE or dieldrin alone does not result in the
      depressed endocrine status and poor reproductive success reported in highly
      organochlorine pesticide-contaminated environments in Central Florida, USA.

PMID- 17521140
TI  - Effects of using synthetic sea salts when measuring and modeling copper toxicity
      in saltwater toxicity tests.
AB  - Synthetic sea salts are often used to adjust the salinity of effluent, ambient,
      and laboratory water samples to perform toxicity tests with marine and estuarine
      species. The U.S. Environmental Protection Agency (U.S. EPA) provides guidance on
      salinity adjustment in its saltwater test guidelines. The U.S. EPA suggests using
      commercial sea salt brands, such as Forty Fathoms (now named Crystal Sea
      Marinemix, Bioassay Grade), HW Marinemix, or equivalent salts to adjust sample
      salinity. Toxicity testing laboratories in Canada and the United States were
      surveyed to determine synthetic sea salt brand preference. The laboratories (n =
      27) reported using four brands: Crystal Sea Marinemix (56%), HW Marinemix (22%),
      Instant Ocean (11%), and Tropic Marin (11%). Saline solutions (30 g/L) of seven
      synthetic sea salts were analyzed for dissolved copper and dissolved organic
      carbon (DOC) content. Brands included those listed above plus modified general
      purpose salt (modified GP2), Kent Marine, and Red Sea Salt. The synthetic sea
      salts added from < 0.1 to 1.2 microg Cu/L to the solution. Solutions of Crystal
      Sea Marinemix had significantly elevated concentrations of DOC (range = 5.4-6.4
      mg C/L, analysis of variance, Tukey, alpha = 0.05, p < 0.001) while other brands
      generally contained < 1.0 mg C/L. The elevated DOC in Crystal Sea Marinemix was
      expected to reduce copper toxicity. However, the measured dissolved copper
      effective concentration 50% (EC50) for Crystal Sea Marinemix was 9.7 microg Cu/L,
      similar to other tested sea salts. Analysis indicates that the organic matter in
      Crystal Sea Marinemix differs considerably from that of natural organic matter.
      On the basis of consistently adding little DOC and little dissolved copper, GP2
      and Kent Marine are the best salts to use.

PMID- 17521141
TI  - Gill metal binding and stress gene transcription in brown trout (Salmo trutta)
      exposed to metal environments: the effect of pre-exposure in natural populations.
AB  - Brown trout (Salmo trutta) from two native populations from the Roros area in
      Central Norway, acclimated in mining-affected habitats to different levels of
      Cd/Zn and Cu, together with trout from a nearby unaffected river (reference) were
      transferred to a nearby lake with higher levels of Cu, Cd, and Zn than those in
      their respective native rivers. This experiment was conducted to gain information
      about the underlying resistance mechanisms developed in fish exposed to metal
      environments. The focus was on gill metal accumulation and transcription of the
      metal-responsive stress genes metallothionein-A (MT-A), Cu/Zn-superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione
      reductase (GR), and heat shock protein 70 (HSP-70). The only shared response
      shown between the three groups after transfer were Cu accumulation and MT-A
      induction. The Cu-acclimated trout produced mucus to reduce the uptake of Cu into
      the gills. The MT-A levels were highest in the Cd/Zn-acclimated trout both before
      and after transfer. Before transfer, antioxidant transcription (SOD and GPx) was
      higher in gills of Cu-acclimated compared to the Cd/Zn-acclimated trout, but
      increased transcription of antioxidant stress genes was observed after transfer
      in both metal-acclimated groups. The metal-acclimated trout groups also showed an
      increase in the transcription of HSP-70. Compared to the reference population not
      previously exposed to metals, stress gene transcription increased faster in the
      metal-acclimated populations. The exception was induction of CAT, which appeared
      to be depressed after transfer in Cd/Zn-acclimated trout. The data indicate that
      acclimation to chronic metal exposure involves different strategies to cope with
      different metals and that these strategies involve both physiological mechanisms
      (mucus production) as well as metal-related stress gene transcription.

PMID- 17521142
TI  - Comparative neurotoxicity of two energetic compounds,
      hexanitrohexaazaisowurtzitane and hexahydro-1,3,5-trinitro-1,3,5-triazine, in the
      earthworm Eisenia fetida.
AB  - Hexanitrohexaazaisowurtzitane (CL-20) and hexahydro-1,3,5-trinitro-1,3,5-triazine
      (RDX), both energetic compounds, share some degree of structural similarity. A
      noninvasive electrophysiological technique was employed to assess the impacts of
      acute sublethal exposures on impulse conduction in medial (MGF) and lateral (LGF)
      giant nerve fiber pathways of the earthworm Eisenia fetida and to evaluate the
      reversibility of neurotoxic effects. Earthworms were exposed to either 0.02 to
      2.15 microg/cm2 of CL-20 or 0.04 to 5.35 microg/cm2 of RDX, for 1 to 14 d, on
      moistened filter paper. Conduction velocities of MGF and LGF were recorded on a
      digital oscilloscope before and after exposure. Results indicate that at exposure
      levels as low as 0.02 microg/cm2 of CL-20 or 0.21 microg/cm2 of RDX, worms
      exhibited physiological impacts such as retardation, stiffness, and body shrink.
      Both MGF and LGF conduction velocities were negatively correlated with increasing
      doses of CL-20 or RDX. However, such neurotoxic effects were alleviated or even
      eliminated within a few days after exposed worms were transferred to an
      uncontaminated environment, indicating that the neurotoxicity is reversible even
      after 6-d exposure. The CL-20 is more potent than RDX, which is consistent with
      previous studies on lethality, growth, and reproduction endpoints in soil
      oligochaetes.

PMID- 17521143
TI  - Kinetic model of cadmium accumulation and elimination and metallothionein
      response in Ruditapes decussatus.
AB  - The aim of the present study was to determine the response of metallothionein
      (MT) during Cd accumulation and elimination in different tissues of the estuarine
      bivalve Ruditapes decussatus exposed to two nominal Cd concentrations (4 and 40
      microg/L) for 40 d, followed by a depuration period of 50 d. Cadmium was
      accumulated in all tissues of R. decussatus at both exposure concentrations, and
      the accumulation was tissue dependent. Use of the kinetic model showed that in
      the gills and remaining tissues, Cd was assimilated faster at the beginning of
      the exposure and decreased with time, possibly limited by the diffusion rate of
      this metal within the cell. In the digestive gland, however, the Cd was
      continuously accumulated. This could reflect that the Cd uptake rate is
      considerably higher than the loss rate and, therefore, that this tissue has a
      higher capacity to accumulate Cd compared to the other two tissues. Moreover, the
      application of this kinetic model in the different subcellular fractions showed
      that the bioconcentration factor was significantly higher in the low-molecular
      weight fraction (where MT is found), suggesting that this fraction binds Cd
      faster, with a high uptake rate (K(u) = 32/d), and eliminates this metal more
      slowly (K(1) = 0.005/d). During the depuration phase, MT decreased simultaneously
      with Cd elimination in all tissues, although with a shorter half-life. In
      conclusion, the MT response prevented Cd in the tissues of R. decussatus from
      interfering in the normal clam metabolism; therefore, MT acts as a detoxification
      mechanism of Cd.

PMID- 17521144
TI  - Relation of diclofop-methyl toxicity and degradation in algae cultures.
AB  - Information on the effects of pesticide degradation on aquatic organisms is
      needed to properly evaluate the ecotoxicity arising from the use of pesticides
      and for aquatic risk assessment. This work evaluated the toxicity of diclofop
      methyl (DM) and its two major metabolites, diclofop (DC) and 4-(2,4
      dichlorophenoxy)-phenol (DP), to three freshwater microalgae, Chlorella
      pyrenoidosa, Chlorella vulgaris, and Scenedesmus obliquus. The degradation of DM
      in the algal suspensions was determined. Diclofop-methyl was rapidly absorbed
      into the cells of the tested algae, in which it was hydrolyzed to DC and further
      degraded to DP. The half-lives derived from the first-order kinetics indicated
      that DP (t1/2 = 2.47-5.80/d) degraded faster than DC (t1/2 = 6.24-12.25/d). The 4
      (2,4-dichlorophenoxy)-phenol was the strongest inhibitor of algal growth,
      followed by DM and DC, as indicated by their EC50 values of 0.17 to 0.25, 0.42 to
      2.23, and 4.76 to 8.89 mg/L, respectively. The evaluation of overall DM toxicity
      to tested algae in the aquatic systems thus needs to take into consideration the
      degradation of DM. A positive relationship appears to exist between the toxicity
      of DM and DC and their degradability in algal suspensions. Such a relationship,
      if confirmed using more pesticides and aquatic organisms, would improve the
      quality and efficiency of the aquatic risk assessment and management associated
      with pesticide use.

PMID- 17521145
TI  - Developmental toxicity in zebrafish (Danio rerio) embryos after exposure to
      manufactured nanomaterials: buckminsterfullerene aggregates (nC60) and fullerol.
AB  - The present paper summarizes, to our knowledge, the first study regarding the
      developmental toxicity of stable buckminsterfullerene aggregates suspended in
      water (nC60) using zebrafish (Danio rerio) as a vertebrate model. Zebrafish
      embryo survival, hatching rate, heartbeat, and pericardial edema were noted and
      described within 96 h of exposure. Fullerol (a hydroxylated C60 derivative,
      C60(OH)16-18) at 50 mg/L did not exert toxicity to zebrafish embryos. In
      contrast, nC60 at 1.5 mg/L delayed zebrafish embryo and larval development,
      decreased survival and hatching rates, and caused pericardial edema. Toxicity was
      mitigated by adding an antioxidant (glutathione), which suggests that a free
      radical-induced mechanism or another form of oxidative stress played a role in
      developmental toxicity.

PMID- 17521146
TI  - Biological uptake of polychlorinated biphenyls by Macoma balthica from sediment
      amended with activated carbon.
AB  - This work characterizes the efficacy of activated carbon amendment in reducing
      polychlorinated biphenyl (PCB) bioavailability to clams (Macoma balthica) from
      field-contaminated sediment (Hunters Point Naval Shipyard, San Francisco Bay, CA,
      USA). Test methods were developed for the use of clams to investigate the effects
      of sediment amendment on biological uptake. Sediment was mixed with activated
      carbon for one month. Bioaccumulation tests (28 d) were employed to assess the
      relationships between carbon dose and carbon particle size on observed reductions
      in clam biological uptake of PCBs. Extraction and cleanup protocols were
      developed for the clam tissue. Efficacy of activated carbon treatment was found
      to increase with both increasing carbon dose and decreasing carbon particle size.
      Average reductions in bioaccumulation of 22, 64, and 84% relative to untreated
      Hunters Point sediment were observed for carbon amendments of 0.34, 1.7, and
      3.4%, respectively. Average bioaccumulation reductions of 41, 73, and 89% were
      observed for amendments (dose = 1.7% dry wt) with carbon particles of 180 to 250,
      75 to 180, and 25 to 75 microm, respectively, in diameter, indicating kinetic
      phenomena in these tests. Additionally, a biodynamic model quantifying clam PCB
      uptake from water and sediment as well as loss through elimination provided a
      good fit of experimental data. Model predictions suggest that the sediment
      ingestion route contributed 80 to 95% of the PCB burdens in the clams.

PMID- 17521147
TI  - Immunotoxicity of the commercial polybrominated diphenyl ether mixture DE-71 in
      ranch mink (Mustela vison).
AB  - Polybrominated diphenyl ethers (PBDEs) are persistent, bioaccumulative,
      organohalogen compounds that are increasing exponentially in the Great Lakes
      (Canada/USA) biota. The present study was undertaken to examine the immunological
      effects of a commercial PBDE mixture in ranch mink (Mustela vison). Twenty-week
      old mink (n = 10 mink/group) were exposed to 0, 1, 5, or 10 ppm of DE-71 through
      their diet for eight weeks. The phytohemagglutinin-induced cutaneous reaction,
      and antibodies specific to keyhole limpet hemocyanin conjugated to dinitrophenol
      were measured. Liver microsomal ethoxyresorufin-O-deethylase (EROD) activity also
      was measured. Organs were weighed and spleens were examined histologically. No
      differences were found in the PHA-induced skin response in exposed mink; mink in
      the two highest treatments exhibited significant increases in antibody production
      over control mink. Systemic toxicity was apparent; significant body weight
      reductions were found in mink exposed to 5 and 10 ppm of DE-71. Exposed mink had
      significantly larger relative spleen, adrenal, and liver masses than control
      mink. Spleens of mink exposed to 10 ppm of DE-71 had significantly increased
      germinal center development and incidence of B-cell hyperplasia. The activity of
      EROD was induced in all treated mink relative to controls and was positively
      associated with the liver somatic index. Hematocrit in mink from the two highest
      exposure groups was significantly lower than control mink. Percentage neutrophils
      increased and percentage lymphocytes decreased significantly in mink from the
      higher two dosage groups. Our findings have direct relevance to wild mink in the
      Great Lakes ecosystem, because mink are top predators of the aquatic food web,
      providing evidence for the vulnerability of this species to the effects of
      environmental PBDE mixtures.

PMID- 17521148
TI  - The relationship between cholinesterase inhibition and two types of swimming
      performance in chlorpyrifos-exposed coho salmon (Oncorhynchus kisutch).
AB  - Brain acetylcholinesterase (AChE) activity was evaluated after two different
      swimming tests in coho salmon (Oncorhynchus kisutch; 238 +/- 5 g) given 96-h
      exposures to 0, 5, 10, 20, or 40 microg/L of chlorpyrifos. Brain AChE activity
      decreased in a concentration-dependent manner (AChE activities were 81.8, 52.2,
      37.3, and 21.3% of control for the 5, 10, 20, and 40 microg/L exposures,
      respectively), whereas swimming performance was impaired after a threshold of
      AChE impairment was reached. Specifically, for swimming performance (U(crit))
      measured using the established ramp-U(crit) test (duration, 152 +/- 8 min), this
      threshold occurred with AChE activity of 68.5% +/- 18.1% of control. For a rapid
      acceleration test (U(deltav), where V represents velocity; 27.6 +/- 0.8 min),
      this value was 52.6% +/- 15.4% of control. Both swim protocols resulted in
      similar maximum swim speeds (control ramp-U(crit) and U(deltav) values of 3.44 +/
      0.09 and 3.71 +/- 0.13 body lengths/s, respectively), and performance was
      significantly reduced after 20 and 40 microg/L exposures in both groups (ramp
      U(crit) values: 86.4 and 83.6 %, respectively, of control; U(deltav) values: 85.2
      and 77.8%, rsepectively, of control). Although both tests yielded similar swim
      speeds, postexercise plasma lactate concentrations were greater for the U(deltav)
      test (11.3 +/- 0.6 vs 8.6 +/- 0.5 mmol/L), indicating a greater anaerobic effort.
      This increase was exaggerated after 10 microg/L of chlorpyrifos (14.6 +/- 1.3
      mmol/L), indicating that anaerobic muscle was used to attain the same speed.
      Given the threshold relationship between AChE inhibition and swimming
      performance, coho salmon appear able to maintain integrated swimming activity
      despite significant impairment of an underlying neurological control mechanism.

PMID- 17521149
TI  - Environmentally relevant concentrations of ethynylestradiol cause female-biased
      sex ratios in Xenopus tropicalis and Rana temporaria.
AB  - The susceptibility of Xenopus (Silurana) tropicalis and Rana temporaria to
      ethynylestradiol (EE2), a potent estrogenic pharmaceutical and environmental
      pollutant, was investigated. Larval EE2 exposure caused female-biased sex ratios
      at concentrations as low as 0.06 nM, which is comparable to levels found in the
      environment. The susceptibility of the two frog species to EE2 was comparable,
      supporting the use of X. tropicalis as a model organism for research on
      developmental reproductive toxicity of estrogenic pollutants.

PMID- 17521150
TI  - Genetic impoverishment in laboratory cultures of the test organism Chironomus
      riparius.
AB  - Genetic diversity among laboratory and field populations of Chironomus riparius
      was investigated using microsatellite DNA analysis. Individuals of midge cultures
      reared in 10 different laboratories showed a clear reduction in the number of
      alleles per locus and in the level of heterozygosity compared to two natural
      populations sampled in southern Germany. To reconstruct the rate of genetic
      impoverishment under laboratory conditions, genetic diversity was monitored in a
      C. riparius laboratory population for 23 generations. Additionally, 11
      populations originating from different laboratories were crossed, and genetic
      diversity was compared among pure, crossed, and natural populations. The results
      demonstrate that C. riparius strains used in standard toxicity tests exhibit low
      levels of genetic variability. In addition, our experiments show that refreshment
      of stocks with individuals from other laboratories is not sufficient to restore
      genetic variation. Potential consequences of genetic impoverishment and
      improvements for toxicological bioassays are discussed.

PMID- 17521151
TI  - Biokinetics and tolerance development of toxic metals in Daphnia magna.
AB  - Daphnia magna is widespread in many freshwater systems of temperate regions and
      frequently is used to test metal toxicity. Recently, studies have been performed
      to determine metal biokinetics and development of tolerance in this important
      zooplankton species. In the present paper, we review the recent progress in these
      areas and suggest possible directions for future studies. Substantial differences
      exist in aqueous uptake, dietary assimilation, and elimination of several metals
      (Cd, Se, Zn, Ag, Hg, and MeHg) by D. magna. The routes of uptake are metal
      specific, with Se and MeHg being accumulated predominantly through diet. All
      metals except Ag can be biomagnified from algae to D. magna, providing that metal
      concentrations in algae and algal food density are relatively low. Methylmercury
      is biomagnified in all situations. As a route for metal elimination in D. magna,
      maternal transfer is especially important for Se, Zn, and MeHg. On the other
      hand, the effect of single-generation exposure to metals on D. magna is very
      different from multigeneration exposure, which often results in a significantly
      higher metal tolerance. Moreover, D. magna easily loses metal tolerance developed
      through long-term exposure. Recovery from metal stress can temporarily increase
      the sensitivity of D. magna to metal toxicity. Finally, metallothionein-like
      protein is responsible for minimizing metal toxicity in D. magna. The results
      inferred from these studies can be extrapolated to other aquatic invertebrates as
      well as to other pollutants in the aquatic environment.

PMID- 17521152
TI  - Role of ethylenediaminetetraacetic acid on lead uptake and translocation by
      tumbleweed (salsola kali L.).
AB  - Tumbleweed plants (Salsola kali L.) grown in agar and liquid media demonstrated a
      high capacity to accumulate Pb in their different parts without affecting
      biomass. Whereas shoot elongation and biomass were not significantly affected by
      high tissue concentrations of Pb, root growth was significantly affected relative
      to controls. Roots, stems, and leaves demonstrated Pb concentrations of 31,000,
      5,500, and 2,100 mg/kg dry weight, respectively, when plants were grown in the
      agar medium containing 80 mg Pb/L. Application of ethylenediaminetetraacetic acid
      (EDTA) to Pb-contaminated media dramatically reduced the total acquisition of Pb
      from both types of media. However, EDTA significantly increased the translocation
      of Pb from roots to the aerial parts, as evidenced by a multifold increase (23-
      and 155-fold for agar and liquid media, respectively) in the translocation
      concentration factor. The concentration of the antioxidant thiol compounds
      significantly increased (p < 0.05) in plants grown with uncomplexed Pb treatments
      relative to control plants. Scanning-electron microscopy and electron dispersive
      x-ray spectroscopic evaluation of leaf samples demonstrated an interesting
      pattern of Pb translocation in the presence or absence of EDTA. Large Pb crystals
      were found across the leaf tissues (palisade, spongy parenchyma, and conducting
      tissues) in the absence of EDTA. Lead nanoparticles also were seen when plants
      were grown in Pb-EDTA solution. Ultramicroscopic features of tumbleweed provide
      clear evidence for the unrestricted conduction of Pb from the root to the aerial
      parts, and this property makes the plant a good candidate for phytoremediation.

PMID- 17521153
TI  - Deer exposed to exceptionally high concentrations of lead near the Continental
      Mine in Idaho, USA.
AB  - Habitat surrounding the inactive Continental Mine in northern Idaho, USA,
      supports bear (Ursus arctos, Ursus americanus), moose (Alces alces), elk (Cervus
      elaphus), woodland caribou (Rangifer tarandus caribou), and abundant mule
      (Odocoileus hemionus) and white-tailed deer (Odocoileus virginianus). Tailings on
      the mining site were capped and remediated in 2003 to reduce environmental
      exposure of surrounding soil and sediments of Blue Joe Creek, downslope of the
      mine. Before capping, the mean Pb concentration in deer pellets collected on-site
      was 920 mg/kg of Pb (dry wt). This exposure, if chronic, would be comparable to
      an exposure that could be lethal to cattle or horses. Surprisingly, the mean
      pellet Pb concentration of 950 mg/kg in 2004 was as high as it was before
      remediation, and it was related to a high rate of soil ingestion. Mean soil
      content of the pellets collected from the capped site in 2004 was 22% dry weight,
      estimated from the acid-insoluble ash, a marker of soil ingestion. Clumps of sand
      and bits of rock were observed inside some of the pellets, and Pb concentrations
      in the pellets were correlated (p < 0.05) with soil content. Although terrestrial
      risk assessments generally estimate exposure from diets and from incidentally
      ingested soil. the deer at this site were directly ingesting contaminated soil or
      mining waste. The mean Pb concentration of this ingested soil was estimated as
      6,700 mg/kg and the maximum as 25,000 mg/kg, well above the Pb concentrations
      measured in the remediated cap. The deer seemed to be ingesting soil or mining
      waste from one or more small but highly contaminated sources located beyond the
      remediated cap.

PMID- 17521154
TI  - Distribution and accumulation of mercury in tissues of captive-reared common loon
      (Gavia immer) chicks.
AB  - We determined the distribution and accumulation of Hg in tissues of common loon
      (Gavia immer) chicks maintained for up to 15 weeks on either a control diet with
      no added methylmercury chloride (MeHgCl) or one containing either 0.4 or 1.2
      microg Hg (as MeHgCl)/g wet-weight food. Total Hg and MeHg tissue concentrations
      were strongly positively correlated (r2 > 0.95) with the amount of Hg delivered
      to individual chicks throughout the course of the experiment. The pattern of
      differential Hg concentration in internal tissues was consistent within each
      treatment: Liver > kidney > muscle > carcass > brain. Feather Hg concentrations
      were consistently higher than those of internal tissues and represented an
      important route of Hg elimination. Feather mass accounted for 4.3% +/- 0.1%
      (average +/- standard error) of body mass, yet 27.3% +/- 2.6% of total Hg intake
      was excreted into feathers. Our calculations indicate that 26.7% +/- 4.9% of
      ingested Hg was not accounted for and, thus, either was never absorbed or was
      absorbed and subsequently eliminated in feces. With the additional excretion into
      feathers, 54% of ingested Hg was excreted. Demethylation was evident in the liver
      at all treatment levels and in the kidneys of chicks dosed at 1.2 microg Hg/g.
      Mercury concentrations were strongly positively correlated (r2 > or = 0.95) among
      internal tissues and with blood Hg concentration. Mercury concentrations of
      secondary feathers were moderately correlated (r2 = 0.82-0.93) with internal
      tissues. We supply regression models that may be used to provide perspective and
      a useful means of interpreting the variety of measures of Hg exposure reported in
      the literature.

PMID- 17521155
TI  - Adult tree swallow (Tachycineta bicolor) survival on the polychlorinated biphenyl
      contaminated Housatonic River, Massachusetts, USA.
AB  - Tree swallows (Tachycineta bicolor) were captured and banded at six sites that
      differed in polychlorinated biphenyl (PCB) contamination levels in the Housatonic
      River watershed, western Massachusetts, USA, from 2000 through 2004 to test the
      prediction that apparent survival rates of females in more contaminated areas
      were lower than those from less contaminated areas. We also tested whether
      plumage coloration affected over-winter survival and whether concentrations of
      PCBs in eggs differed between birds that did and that did not return the
      following year. Apparent survival rates were calculated using mark-recapture
      methods and compared using Akaike's Information Criterion. Model-adjusted
      survival rates ranged from 0.365 to 0.467 for PCB-contaminated females and
      between 0.404 and 0.476 for reference females. Models with either survival or
      capture probability modeled as functions of treatment (degree of PCB
      contamination), year, and age received some support. The model-averaged parameter
      estimate reflecting a treatment effect for high-PCB birds was negative (beta = 
      0.046, SE(beta) = 0.0939). Fifty-four percent of the total model weights involved
      models in which survival was a function of PCB treatment. Eggs were collected for
      contaminant analyses from a random sample of females that did and that did not
      return the following year. Concentrations of total PCBs were the same or higher
      in the eggs of females that returned compared to the eggs of those that did not
      return at both the highly and the moderately contaminated PCB sites. This may
      have resulted from higher-quality females with higher lipid reserves being more
      likely than lower-quality females to return the following year. Percentage lipid
      was positively correlated with total PCBs in eggs. Survival rates were similar
      among swallows with brown versus blue plumage.

PMID- 17521156
TI  - Microcystin accumulation in freshwater bivalves from Lake Taihu, China, and the
      potential risk to human consumption.
AB  - The potential risk through ingestion of microcystins (MC) in contaminated
      mollusks has not been well studied. The present paper studied seasonal changes of
      MC content (determined by liquid chromatography-mass spectrometry) in various
      organs of three species of bivalves (Cristaria plicata, Hyriopsis cumingii, and
      Lamprotula leai) in Lake Taihu, China, where toxic cyanobacterial blooms
      occurred. Coinciding with peaks of seston MC (maximum, 5.7 microg/L) and MC in
      cyanobacterial blooms (maximum, 0.534 mg/g), most organs showed sharp MC peaks
      during the summer, indicating both fast uptake and fast depuration by bivalves.
      Because hepatopancreas and intestine had considerably higher MC content than
      other organs, they are the most dangerous for human consumption. Both the present
      and previous studies show that the hepatopancreatic MC and total tissue MC often
      are correlated in various aquatic invertebrates. During the peak of the
      cyanobacterial blooms, C. plicata had higher hepatopancreatic MC content than the
      other bivalves, whereas H. cumingii had higher intestinal MC content than the
      other bivalves. Estimated daily intakes for humans from the consumption of whole
      tissues of the three bivalves were 0.48 to 0.94 microg MC-LR equivalent/kg body
      weight (12- to 23.5-fold the tolerable daily intake value proposed by the World
      Health Organization), which indicates a high risk for humans consuming these
      bivalves.

PMID- 17521157
TI  - Causes of water toxicity to Hyalella azteca in the New River, California, USA.
AB  - The New River (CA, USA) was created in 1905 to 1907 when the Colorado River
      washed out diversionary works and flowed into the Salton Basin, creating the
      Salton Sea. Approximately 70% of the river's current flow is agricultural
      wastewater from the Imperial Valley. The river is contaminated with pesticides,
      industrial organic chemicals, metals, nutrients, bacteria, and silt. Monitoring
      for the State of California Surface Water Ambient Monitoring Program has
      indicated persistent water column toxicity to the epibenthic amphipod Hyalella
      azteca. Four toxicity identification evaluations (TIEs), along with chemical
      analyses, were performed, and the results indicated multiple and varying causes
      of toxicity. The first two TIEs characterized the causes of toxicity as a
      combination of metals and organics, but only the second sample contained enough
      total copper to contribute to toxicity. The third TIE used an emerging method for
      characterizing and identifying toxicity caused by pyrethroid pesticides. This TIE
      characterized organics as the cause of toxicity, and a carboxylesterase enzyme
      treatment further identified the cause of toxicity as pyrethroids. The final TIE
      used the enzyme and Phase II procedures to identify cypermethrin as the cause of
      toxicity. The TIE results demonstrate the evolving causes of toxicity in the New
      River and should assist regulators with implementing the total maximum daily load
      process for pesticides, particularly pyrethroids. Further research will determine
      if pyrethroids and other New River contaminants are having an impact on the
      Salton Sea.

PMID- 17521158
TI  - Dioxygen activation at non-heme iron: insights from rapid kinetic studies.
AB  - One of the common biochemical pathways of binding and activation of dioxygen
      involves non-heme iron centers. The enzyme cycles usually start with an iron(II)
      or diiron(II) state and traverse via several intermediates (detected or
      postulated) such as (di)iron(III)-superoxo, (di)iron(III)-(hydro)peroxo,
      iron(III)iron(IV)-oxo, and (di)iron(IV)-oxo species, some of which are
      responsible for substrate oxidation. In this Account, we present results of
      kinetic and mechanistic studies of dioxygen binding and activation reactions of
      model inorganic iron compounds. The number of iron centers, their coordination
      number, and the steric and electronic properties of the ligands were varied in
      several series of well-characterized complexes that provided reactive manifolds
      modeling the function of native non-heme iron enzymes. Time-resolved cryogenic
      stopped-flow spectrophotometry permitted the identification of kinetically
      competent intermediates in these systems. Inner-sphere mechanisms dominated the
      chemistry of dioxygen binding, intermediate transformations, and substrate
      oxidation as most of these processes were controlled by the rates of ligand
      substitution at the iron centers.

PMID- 17521159
TI  - Ionic liquids: the link to high-temperature molten salts?
AB  - Due to their wide thermal windows, ionic liquids can be regarded as the missing
      link between aqueous/organic solutions and high-temperature molten salts. They
      can be employed efficiently for the coating of other metals with thin layers of
      tantalum, aluminum, and presumably many others at reasonable temperatures by
      electrochemical means. The development of ionic liquids, especially air and water
      stable ones, has opened the door for the electrodeposition of reactive elements
      such as, for example, Al, Ta, and Si, which in the past were only accessible
      using high-temperature molten salts or, in part, organic solvents.

PMID- 17521160
TI  - From phage display to magnetophage, a new tool for magnetic resonance molecular
      imaging.
AB  - Phage display, an extremely promising technology in the context of molecular
      imaging, allows for the selection of peptides interacting with virtually any
      target from a heterogeneous mixture of bacteriophages. In this work, we propose
      the concept of magnetophages, obtained by covalent coupling of ultrasmall
      particles of iron oxide (USPIO) to the proteins of the phage wall. To validate
      magnetophages as a magnetic resonance imaging contrast agent (MRI), we have used
      as a prototype the clone E3 because of its specific affinity for
      phosphatidylserine, a marker of apoptosis. Enzyme-linked immunosorbent assay
      showed that E3 magnetophages incubated with phosphatidylserine retained the
      properties of the nonmagnetically labeled phages. The usefulness of magnetophages
      as an MRI contrast agent was estimated by incubation with phosphatidylcholine and
      phosphatidylserine or with apoptotic and control cells. Under these conditions,
      E3 magnetophages allow the discrimination of phosphatidylserine from
      phosphatidylcholine and of apoptotic cells from control ones. Injected in vivo,
      magnetophages are rapidly cleared from the blood stream and internalized by the
      phagocytic cells of the liver. To abrogate this problem, USPIO were pegylated to
      obtain stealthy E3-PEG-magnetophages, invisible to phagocytic cells, which were
      successfully targeted to apoptotic liver. If this feature demonstrated for E3
      magnetophages can be extrapolated to other phage display selected entities,
      magnetophages become an original system which allows validation of the candidate
      binding peptides before their synthesis is considered. The concept of the
      magnetophage could be extended to other imaging modalities by replacing USPIO
      with an adequate reporter (i.e., radiolabeled phages).

PMID- 17521161
TI  - Unusual cell adhesion and antithrombogenic behavior of citric acid-cross-linked
      collagen matrices.
AB  - We have developed a novel biodegradable matrix that has unusual cell adhesion and
      antithrombogenic properties. The prepared biodegradable matrix was alkali-treated
      collagen (AlCol) cross-linked with citric acid derivative (CAD), named as AlCol
      CAD. The swelling ratio of AlCol-CAD decreased with increasing CAD concentration,
      but with a further increase of the CAD concentration, the swelling ratio of AlCol
      CAD also began to increase; this behavior showed a point where the swelling ratio
      reached a minimum value before increasing. The highest shrinkage states of 7.5%,
      15%, and 30% (w/v) in AlCol-CAD were observed at CAD concentrations of 10, 20,
      and 40 mM, respectively, and moreover, the residual amino groups in AlCol-CAD
      were found to decrease with increasing CAD concentration. On the other hand,
      increases in carboxyl groups of 7.5% and 15% (w/v) in AlCol-CAD were found at CAD
      concentrations higher than 10 and 20 mM, respectively, whereas, at CAD
      concentrations from 10 to 40 mM, no significant change of the carboxyl groups was
      observed in 30% (w/v) AlCol-CAD. Human umbilical vein endothelial cell (HUVEC)
      adhesion on 15% (w/v) AlCol-CAD increased with increasing CAD concentration up to
      20 mM and then slightly decreased. In the case of 30% (w/v) AlCol-CAD, the number
      of adhered HUVECs on AlCol-CAD increased with increasing CAD concentration.
      Furthermore, it was observed that HUVECs had excellent cell proliferation on 15%
      (w/v) AlCol-CAD at CAD concentrations of 20 and 40 mM, after incubation for 7
      days. No thrombus formation was observed on 15% (w/v) AlCol-CAD at CAD
      concentrations above 20 mM. These results suggested that the 15% (w/v) AlCol-CAD
      at CAD concentrations above 20 mM has both HUVEC adhesion and antithrombogenic
      properties.

PMID- 17521162
TI  - Cellulose/water: liquid/gas and liquid/liquid phase equilibria and their
      consistent modeling.
AB  - Liquid/liquid and liquid/gas equilibria were measured for the water/cellulose
      system at 80 degrees C using three different polymer samples. For these
      experiments we prepared cellulose films of approximately 20-25 microm in
      thickness and determined their equilibrium swelling in water. Thereafter the
      polymer concentration in the mixed phase was increased by means of a stepwise
      removal of the volatile component, and the equilibrium vapor pressures were
      measured using an automated combination of head space sampling and gas
      chromatography. Contrary to the usual behavior of polymers, the swelling of
      cellulose increases as its molar mass becomes larger. The Flory-Huggins
      interaction parameters calculated from the measured vapor pressures pass a
      pronounced minimum as a function of composition; for high cellulose contents they
      are negative, whereas they become positive for water-rich mixtures. All
      experimental findings are consistently interpreted by means of an approach
      accounting explicitly for the effects of chain connectivity and for the ability
      of macromolecules to respond to environmental changes by conformational
      rearrangement.

PMID- 17521163
TI  - Using prior knowledge in the determination of macromolecular size-distributions
      by analytical ultracentrifugation.
AB  - Analytical ultracentrifugation has reemerged as a widely used tool for the study
      of ensembles of biological macromolecules to understand, for example, their size
      distribution and interactions in free solution. Such information can be obtained
      from the mathematical analysis of the concentration and signal gradients across
      the solution column and their evolution in time generated as a result of the
      gravitational force. In sedimentation velocity analytical ultracentrifugation,
      this analysis is frequently conducted using high resolution, diffusion
      deconvoluted sedimentation coefficient distributions. They are based on Fredholm
      integral equations, which are ill-posed unless stabilized by regularization. In
      many fields, maximum entropy and Tikhonov-Phillips regularization are well
      established and powerful approaches that calculate the most parsimonious
      distribution consistent with the data and prior knowledge, in accordance with
      Occam's razor. In the implementations available in analytical
      ultracentrifugation, to date, the basic assumption implied is that all
      sedimentation coefficients are equally likely and that the information retrieved
      should be condensed to the least amount possible. Frequently, however, more
      detailed distributions would be warranted by specific detailed prior knowledge on
      the macromolecular ensemble under study, such as the expectation of the sample to
      be monodisperse or paucidisperse or the expectation for the migration to
      establish a bimodal sedimentation pattern based on Gilbert-Jenkins' theory for
      the migration of chemically reacting systems. So far, such prior knowledge has
      remained largely unused in the calculation of the sedimentation coefficient or
      molecular weight distributions or was only applied as constraints. In the present
      paper, we examine how prior expectations can be built directly into the
      computational data analysis, conservatively in a way that honors the complete
      information of the experimental data, whether or not consistent with the prior
      expectation. Consistent with analogous results in other fields, we find that the
      use of available prior knowledge can have a dramatic effect on the resulting
      molecular weight, sedimentation coefficient, and size-and-shape distributions and
      can significantly increase both their sensitivity and their resolution. Further,
      the use of multiple alternative prior information allows us to probe the range of
      possible interpretations consistent with the data.

PMID- 17521164
TI  - Composite nanoparticles based on hyaluronic acid chemically cross-linked with
      alpha,beta-polyaspartylhydrazide.
AB  - In this paper, new composite nanoparticles based on hyaluronic acid (HA)
      chemically cross-linked with alpha,beta-polyaspartylhydrazide (PAHy) were
      prepared by the use of a reversed-phase microemulsion technique. HA-PAHy
      nanoparticles were characterized by FT-IR spectroscopy, confirming the occurrence
      of the chemical cross-linking, dimensional analysis, and transmission electron
      micrography, showing a sub-micrometer size and spherical shape. Zeta potential
      measurements demonstrated the presence of HA on the nanoparticle surface. A
      remarkable affinity of the obtained nanoparticles toward aqueous media that
      simulate some biological fluids was found. Stability studies showed the absence
      of chemical degradation in various media, while in the presence of hyaluronidase,
      a partial degradation occurred. Cell compatibility was evaluated by performing in
      vitro assays on human chronic myelogenous leukaemia cells (K-562) chosen as a
      model cell line and a haemolytic test. HA-PAHy nanoparticles were also able to
      entrap 5-fluorouracil, chosen as a model drug, and release it in a simulated
      physiological fluid and in human plasma with a mechanism essentially controlled
      by a Fickian diffusion.

PMID- 17521165
TI  - Controllable degradation product migration from cross-linked biomedical polyester
      ethers through predetermined alterations in copolymer composition.
AB  - Uniformly degrading biomaterials with adjustable degradation product migration
      rates were customized by combining the advantages of cross-linked poly(epsilon
      caprolactone) with the hydrophilic character of poly(1,5-dioxepan-2-one).
      Hydrolytic degradation of these random cross-linked networks using 2,2'-bis
      (epsilon-caprolactone-4-yl) propane (BCP) as the cross-linking agent was studied
      for up to 546 days in phosphate buffer solution at pH 7.4 and 37 degrees C. The
      hydrophilicity of the materials was altered by varying the copolymer
      compositions. After different hydrolysis times the materials were characterized,
      and the degradation products were extracted from the buffer solution and
      analyzed. Fourier transform infrared spectroscopy, differential scanning
      calorimetry, atomic force microscopy, scanning electron microscopy, and gas
      chromatography-mass spectrometry were used to observe the changes taking place
      during the hydrolysis. From the results it was concluded that degradation
      profiles and migration of degradation products are controllable by tailoring the
      hydrophilicity of cross-linked polyester-ether networks.

PMID- 17521166
TI  - Analytical profiling of biosynthetic intermediates involved in the gentamicin
      pathway of Micromonospora echinospora by high-performance liquid chromatography
      using electrospray ionization mass spectrometric detection.
AB  - In the present study, we developed a sensitive and highly selective method of
      detecting the biosynthetic intermediates involved in the gentamicin pathway from
      a cell culture of Micromonospora echinospora. A novel extraction method utilizing
      a dual solid-phase extraction (SPE) technique was employed to purify and recover
      all of the gentamicin-related components from the cell culture broth, and high
      performance liquid chromatography (HPLC) coupled with electrospray ionization
      mass spectrometry (ESI-MS/MS) was used to analyze the extractant for gentamicin
      intermediates. The pH of the culture broth was adjusted to an acidic condition of
      pH 2 prior to the extraction. The samples were first cleaned with a reversed
      phase AccuBOND C(18) cartridge, and then the aminoglycosidic components were
      purified using a cationic exchanger OASIS MCX cartridge. The detection limit of a
      gentamicin standard spiked in blank medium processed by this method was found to
      be approximately 5 ng for each component of the gentamicin C complex, and the
      mean recovery for each component of standard gentamicin was above 91% when
      analyzed by HPLC-ESI-MS/MS. We further demonstrated that this method enables the
      analytical profiling of the gentamicin-related compounds produced by wild-type M.
      echinospora ATCC 15835, which mainly produces the gentamicin C complex, and the
      UV-induced mutant strain KCTC 10506BP, which produces gentamicin B as the major
      product. Seven intermediates (paromamine, gentamicin A2, B, X2, A, JI-20A, and JI
      20B) besides the gentamicin C complex were detected in the culture broth of both
      M. echinospora strains when analyzed by MS/MS for the distinct fragmentation
      patterns of each gentamicin component. This report displays the first example of
      the HPLC profiling in a wide range of structurally related biosynthetic
      intermediates involved in the gentamicin pathway.

PMID- 17521167
TI  - Virtual polymorphism: finding divergent peptide matches in mass spectrometry
      data.
AB  - The prevailing method of analyzing tandem-MS data for protein identification
      involves the comparison of peptide molecular weight and fragmentation data to
      theoretically predicted values, based on known protein sequences in databases.
      This is generally effective since proteins from most species under study are in
      the database or have sufficient homology to allow significant matching. We have
      encountered difficulties identifying proteins from fungal species Alternaria
      alternata due to significant interspecies protein sequence differences
      (divergence) and its absence from the database. This common household mold causes
      asthma and allergy problems, but the genome has not been sequenced. De novo
      sequencing and error-tolerant methods can facilitate protein identifications in
      divergent, unsequenced species. But these standard methods can be laborious and
      only allow single amino acid substitution, respectively. We have developed an
      alternative approach focusing on database engineering, predicting biologically
      rational polymorphism using statistically weighted amino acid substitution
      information held in BLOSUM62. Like other second pass methods, it is based on the
      initially identified protein. However, this approach allows more control over
      sequences to be considered, including multiple changes per peptide. The results
      show considerable improvement for routine protein identification and the
      potential for rescuing otherwise unconvincing identifications in unusually
      divergent species.

PMID- 17521168
TI  - Batch fabrication of atomic force microscopy probes with recessed integrated ring
      microelectrodes at a wafer level.
AB  - A batch fabrication process at the wafer-level integrating ring microelectrodes
      into atomic force microscopy (AFM) tips is presented. The fabrication process
      results in bifunctional scanning probes combining atomic force microscopy with
      scanning electrochemical microscopy (AFM-SECM) with a ring microelectrode
      integrated at a defined distance above the apex of the AFM tip. Silicon carbide
      is used as AFM tip material, resulting in reduced mechanical tip wear for
      extended usage. The presented approach for the probe fabrication is based on
      batch processing using standard microfabrication techniques, which provides
      bifunctional scanning probes at a wafer scale and at low cost. Additional
      benefits of batch fabrication include the high processing reproducibility,
      uniformity, and tuning of the physical properties of the cantilever for optimized
      AFM dynamic mode operation. The performance of batch-fabricated bifunctional
      probes was demonstrated by simultaneous imaging micropatterned platinum
      structures at a silicon dioxide substrate in intermittent (dynamic) and contact
      mode, respectively, and feedback mode SECM. In both, intermittent and contact
      mode, the bifunctional probes provided reliable correlated electrochemical and
      topographical data. In addition, simulations of the diffusion-limited steady
      state currents at the integrated electrode using finite element methods were
      performed for characterizing the developed probes.

PMID- 17521169
TI  - Lesion recognition and cleavage by endonuclease V: a single-molecule study.
AB  - Endonuclease V (endo V) recognizes and cleaves deoxyinosine in deaminated DNA.
      These enzymatic activities are precursors of DNA repair and are fueled by metal
      ions such as Ca2+ and Mg2+, with the former being associated with protein binding
      and the latter with DNA cleavage. Using the technique of fluorescence resonance
      energy transfer (FRET), we determined the single-molecule kinetics of endo V in a
      catalytic cycle using a substrate of deoxyinosine-containing single-stranded DNA
      (ssDNA). The ssDNA was labeled with TAMRA, a fluorescence donor, while the endo V
      was labeled with Cy5, a fluorescence acceptor. The time lapses of FRET, resulting
      from the sequential association, recognition, and dissociation of the
      deoxyinosine by the endo V, were determined at 5.9, 14.5, and 9.1 s,
      respectively, in the presence of Mg2+. In contrast, the process of deoxyinosine
      recognition appeared little affected by the metal type. The prolonged association
      and dissociation events in the presence of the Ca2+-Mg2+ combination, as compared
      to that of Mg2+ alone, support the hypothesis that endo V has two metal binding
      sites to regulate its enzymatic activities.

PMID- 17521170
TI  - Amyloid formation via supramolecular peptide assemblies.
AB  - Amyloid fibrils have been classically defined as linear, nonbranched polymeric
      proteins with a cross beta-sheet structure and the ability to alter the optical
      properties of the amyloid-specific dye Congo Red. Mounting evidence suggests that
      soluble oligomeric peptide assemblies approximately 2-20 nm in diameter are
      critical intermediates in amyloid formation. Using a pathogenic prion protein
      peptide comprised of residues 23-144, we demonstrate that, under quiescent but
      not agitated conditions, much larger globular assemblies up to 1 mum in diameter
      are made. These globules precede fibril formation and directly interact with
      growing fibril bundles. Fibrils made via these large spherical peptide assemblies
      displayed a remarkable diversity of ultrastructural features. Fibrillization of
      the Abeta1-40 peptide under similar conditions yielded similar results,
      suggesting a mechanism of general amyloid formation that can proceed through
      intermediates much larger than those previously described. Our data suggest that
      simply changing the physical microenvironment can profoundly influence the
      mechanism of amyloid formation and yield fibrils with novel ultrastructural
      properties.

PMID- 17521171
TI  - Optimization of three- and four-component reactions for polysubstituted
      piperidines: application to the synthesis and preliminary biological screening of
      a prototype library.
AB  - Several solid- and solution-phase strategies were evaluated for the preparation
      of libraries of polysubstituted piperidines of type 7 using the tandem
      aza[4+2]cycloaddition/allylboration multicomponent reaction between 1-aza-4
      boronobutadienes, maleimides, and aldehydes. A novel four-component variant of
      this chemistry was developed in solution phase, and it circumvents the need for
      pre-forming the azabutadiene component. A parallel synthesis coupled with
      compound purification by HPLC with mass-based fraction collection allowed the
      preparation of a library of 944 polysubstituted piperidines in a high degree of
      purity suitable for biological screening. A representative subset of 244
      compounds was screened against a panel of phosphatase enzymes, and despite the
      modest levels of activity obtained, this study demonstrated that piperidines of
      type 7 display the right physical properties (e.g., solubility) to be assayed
      effectively in high-throughput enzymatic tests.

PMID- 17521172
TI  - Scaled second-order perturbation corrections to configuration interaction
      singles: efficient and reliable excitation energy methods.
AB  - Two modifications of the perturbative doubles correction to configuration
      interaction with single substitutions (CIS(D)) are suggested, which are excited
      state analogues of ground state scaled second-order Moller-Plesset (MP2) methods.
      The first approach employs two parameters to scale the two spin components of the
      direct term of CIS(D), starting from the two-parameter spin-component scaled
      (SCS) MP2 ground state, and is termed SCS-CIS(D). An efficient resolution-of-the
      identity (RI) implementation of this approach is described. The second approach
      employs a single parameter to scale only the opposite-spin direct term of CIS(D),
      starting from the one-parameter scaled opposite-spin (SOS) MP2 ground state, and
      is called SOS-CIS(D). By utilizing auxiliary basis expansions and a Laplace
      transform, a fourth-order algorithm for SOS-CIS(D) is described and implemented.
      The parameters that describe SCS-CIS(D) and SOS-CIS(D) are optimized based on a
      training set that includes valence excitations of various organic molecules and
      Rydberg transitions of water and ammonia, and they significantly improve upon
      CIS(D) itself. The accuracy of the two methods is found to be comparable. This
      arises from a strong correlation between the same-spin and the opposite-spin
      portions of the excitation energy terms. The methods are successfully applied to
      the zincbacteriochlorin-bacteriochlorin charge-transfer transition, for which
      time-dependent density functional theory, with presently available exchange
      correlation functionals, is known to fail. The methods are also successfully
      applied to describe various electronic transitions outside of the training set.
      The efficiency of the SOS-CIS(D) and the auxiliary basis implementation of CIS(D)
      and SCS-CIS(D) are confirmed with a series of timing tests.

PMID- 17521174
TI  - Beam action spectroscopy via inelastic scattering.
AB  - In this article, a new technique we call Beam Action Spectroscopy via Inelastic
      Scattering (BASIS) is demonstrated. BASIS takes advantage of the sensitivity of
      rotational state distributions in a supersonic molecular beam to inelastic
      scattering within the beam. We exploit BASIS to achieve increased sensitivity in
      two very different types of experiments. In the first, the UV photodissociation
      spectrum of OClO is recovered by monitoring intensity changes in the pure
      rotational transition of a spectator molecule (OCS) downstream from the nozzle,
      revealing a new vibrational structure in the region between 30,000 and 36,000 cm(
      1). In the second, the mid-IR vibrational spectrum of acetylene is recorded
      simply by monitoring a single pure rotational transition of OCS co-expanded with
      acetylene. The technique may prove particularly fruitful when an excitation
      process produces product dark states that are not easily probed by conventional
      spectroscopy.

PMID- 17521173
TI  - Implementation of the SCC-DFTB method for hybrid QM/MM simulations within the
      amber molecular dynamics package.
AB  - Self-consistent charge density functional tight-binding (SCC-DFTB) is a
      semiempirical method based on density functional theory and has in many cases
      been shown to provide relative energies and geometries comparable in accuracy to
      full DFT or ab initio MP2 calculations using large basis sets. This article shows
      an implementation of the SCC-DFTB method as part of the new QM/MM support in the
      AMBER 9 molecular dynamics program suite. Details of the implementation and
      examples of applications are shown.

PMID- 17521175
TI  - NMR measurements and density functional calculations of the 199Hg-13C spin-spin
      coupling tensor in methylmercury halides.
AB  - The isotropic average, JisoHgC, and the anisotropy, DeltaJHgC, of the 199Hg-13C
      spin-spin coupling tensor in methylmercury halides, CH3HgX (X=Cl, Br, I), were
      determined for the first time by utilizing the NMR spectra of these molecules
      dissolved in liquid crystals. Furthermore, density functional calculations were
      performed using the zeroth-order regular approximation, including also
      dimethylmercury. The temperature-dependence of the JisoHgC couplings in the
      isotropic phase was studied in each case in order to extrapolate their values
      into the liquid crystal state. Good agreement is found between the experimental
      and the calculated DeltaJHgC values as long as solvent effects are considered in
      the computations. Most of the magnitude of DeltaJ can be attributed to the spin
      mechanism of J-coupling, with additional sizable spin-orbital cross terms due to
      electronic spin-orbit coupling.

PMID- 17521176
TI  - Global minimum structures of morse clusters as a function of the range of the
      potential: 81<or=N<or=160.
AB  - We have attempted to find the putative global minimum structures of Morse
      clusters for cluster size N=81-160 as a function of the range of the potential
      (with potential range rho0>or=3.0). Moreover, compared to the results for N<or=80
      listed in the Cambridge Cluster Database, a number of new putative global minima
      are given. A structural and conformational analysis of M100 for different rho0
      was given. The sequences of the global minima as a function of rho0 and N were
      studied, and the zero temperature "phase diagram" was given for an overall view
      of how the global minima depend upon N and rho0.

PMID- 17521177
TI  - The application of 3D-QSAR studies for novel cannabinoid ligands substituted at
      the C1' position of the alkyl side chain on the structural requirements for
      binding to cannabinoid receptors CB1 and CB2.
AB  - A set of 30 novel Delta8-tetrahydrocannabinol and cannabidiol analogues were
      subjected to three-dimensional quantitative structure-activity relationship
      studies using the comparative molecular field analysis (CoMFA) and comparative
      molecular similarity indices analysis (CoMSIA) approaches. Using a combination of
      molecular modeling techniques and NMR spectroscopy, the putative bioactive
      conformation of the most potent cannabinoid (CB) ligand in the training set was
      determined. This conformer was used as the template and CB1 and CB2 pharmacophore
      models were developed. These models were fitted with experimental binding data
      and gave high correlation coefficients. Contour maps of the CB1 and CB2 models of
      CoMFA and CoMSIA approaches show that steric effects dominantly determine the
      binding affinities. The CoMFA and CoMSIA analyses based on the binding affinity
      data of CB ligands at the CB1 and CB2 receptors allowed us to deduce the possible
      optimal binding positions. This information can be used for the design of new CB
      analogues with enhanced activity and other tailored properties.

PMID- 17521178
TI  - New approach for the preparation of efficient DNA cleaving agents: ditopic copper
      platinum complexes based on 3-Clip-Phen and cisplatin.
AB  - The design and synthesis of new heterodinuclear DNA-targeting agents are
      described. The abilities of cisplatin and Cu(3-Clip-Phen) [Cu(1-(1,10
      phenanthrolin-3-yloxy)-3-(1,10-phenanthrolin-8-yloxy)propan-2-amine)Cl2], an
      artificial DNA-cleaving agent, have been combined through their "covalent
      coupling". This strategy has led to bifunctional complexes that are able to
      cleave the DNA in a double-stranded fashion in contrast to Cu(3-Clip-Phen) alone
      and have promising cytotoxicities compared to cisplatin in several cell lines.

PMID- 17521179
TI  - Microtubule-associated protein 1B binds glyceraldehyde-3-phosphate dehydrogenase.
AB  - Microtubule-associated protein 1B, MAP1B, is a major cytoskeletal protein during
      brain development and one of the largest brain MAPs associated with microtubules
      and microfilaments. Here, we identified several proteins that bind to MAP1B via
      immunoprecipitation with a MAP1B-specific antibody, by one and two-dimensional
      gel electrophoresis and subsequent mass spectrometry identification of
      precipitated proteins. In addition to tubulin and actin, a variety of proteins
      were identified. Among these proteins were glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), heat shock protein 8, dihydropyrimidinase related proteins
      2 and 3, protein-L-isoaspartate O-methyltransferase, beta-spectrin, and clathrin
      protein MKIAA0034, linking either directly or indirectly to MAP1B. In particular,
      GAPDH, a key glycolytic enzyme, was bound in large quantity to the heavy chain of
      MAP1B in adult brain tissue. In vitro binding studies confirmed a direct binding
      of GAPDH to MAP1B. In PC12 cells, GAPDH was found in cytoplasm and nuclei and
      partially co-localized with MAP1B. It disappeared from the cytoplasm under
      oxidative stress or after a disruption of cytoskeletal elements after colcemid or
      cytochalasin exposure. GAPDH may be essential in the local energy provision of
      cytoskeletal structures and MAP1B may help to keep this key enzyme close to the
      cytoskeleton.

PMID- 17521180
TI  - Solution behavior of rod-like polyelectrolyte-surfactant aggregates polymerized
      from wormlike micelles.
AB  - The behavior of a rod-like, water-soluble, polyelectrolyte-surfactant aggregate
      system (pC16TVB) in aqueous solution is characterized to determine the
      partitioning of surfactant in these systems and the impact on aggregate
      structure. These aggregates are generated by in situ polymerization of a cationic
      surfactant-hydrotrope wormlike micelle system. This system differs from most
      other polyelectrolyte-surfactant systems in that the monomer groups and the
      surfactant are present in ion pairs in the absence of added salts or counterions,
      so the stoichiometry (with respect to charge) is 1:1 for the system. Therefore,
      after polymerization the surfactant acts as the counterion for the
      polyelectrolyte chains as other counterions (salts) are not available. Despite
      being present in a 1:1 molar ratio, the aggregates are surprisingly stable in
      water (concentrations >600 mg/mL have been achieved). The conformation of the
      polyelectrolyte in the aggregate is analogous to the case of a polymer chain in
      tight confinement in a "tube" or cylindrical pore in which the pore walls are
      attractive--the tube is formed by the surfactant which is free to dissociate from
      the aggregates. A simple model for the structure and partitioning is presented
      and the ability to manipulate the aggregate structure is demonstrated.

PMID- 17521181
TI  - Excited state and charge photogeneration dynamics in conjugated polymers.
AB  - Conjugated polymers are becoming interesting materials for a range of
      optoelectronic applications. However, their often complex electronic and
      structural properties prevent establishment of straightforward property-function
      relationships. In this paper, we summarize recent results on the photophysics and
      excited state dynamics of conjugated polymers, in order to paint a picture of
      exciton formation, quenching, and generation of charge carriers.

PMID- 17521182
TI  - Ultrathin conjugated polymer network films of carbazole functionalized poly(p
      phenylenes) via electropolymerization.
AB  - Ultrathin films of a cross-linked and chemically distinct conjugated poly(p
      phenylene) network via electropolymerization are described. The amphiphilic
      network precursor was synthesized by incorporating the alkoxy carbazole group (
      O(CH2)5Cb) to a poly(p-phenylene) (C6PPPOH) backbone. In order to investigate the
      combined thin film electrochemical and photophysical properties of poly(p
      phenylene)s and polycarbazole conjugated polymers, C6PPPC5Cb was deposited on
      substrates using the Langmuir Blodgett Kuhn (LBK) method. The monolayer isotherm
      of the polymer, C6PPPC5Cb, showed a liquid expanded region slightly different
      from the parent polymer C6PPPOH. Multilayers (up to 30 layers) were transferred
      to different substrates such as quartz, gold coated LaSFN9 and ITO substrates for
      analysis. For conversion to a conjugated polymer network (CPN) film, the
      electroactive carbazole group was electropolymerized using cyclic voltammetry
      (CV) resulting in polycarbazole linking units. The differences in the film
      properties and corresponding changes in the electrochemical behavior indicate the
      importance of film thickness and electron/ion transport process in cross linked
      network films. From the electrochemical studies, the scan rate was found to have
      a considerable effect on electropolymerization with higher oxidation and
      reduction peak values found for the rigid network polymer compared to the
      uncrosslinked polymers.

PMID- 17521183
TI  - Promotion of PEM self-humidifying effect by nanometer-sized sulfated zirconia
      supported Pt catalyst hybrid with sulfonated poly(ether ether ketone).
AB  - A self-humidifying membrane based on low-cost sulfonated poly (ether ether
      ketone) (SPEEK) hybrid with sulfated zirconia (SO4(2-)/ZrO2, SZ)-supported
      platinum catalyst (Pt-SZ catalyst) was investigated for fuel cell applications.
      The SZ particle, a solid-state superacid with hygroscopic and high proton
      conductivity properties, was employed as the catalyst support. The SPEEK/Pt-SZ
      self-humidifying membrane was characterized by TEM and SEM coupled with EDX. FT
      IR was conducted to verify the effect of SPEEK/Pt-SZ membrane on catalytic
      combination of crossover hydrogen and oxygen. To display the advantages of Pt-SZ
      catalyst as the additive, the IEC, water uptake, proton conductivity, single-cell
      performance, and areal resistance measurements were compared between the plain
      SPEEK membrane, SPEEK/Pt-SiO2 membrane, and the SPEEK/Pt-SZ membrane. The
      SPEEK/Pt-SZ membrane exhibited the highest IEC value, proton conductivity, single
      cell performance, and the lowest areal resistance relative to the plain SPEEK and
      SPEEK/Pt-SiO2 membranes. The SPEEK/Pt-SZ self-humidifying membrane exhibited peak
      power density of 1.0 W/cm2 under dry operation condition compared with 0.89 W/cm2
      and 0.58 W/cm2 of SPEEK/Pt-SiO2 and plain SPEEK membranes, respectively. The
      incorporation of the catalytic, hygroscopic and proton conductive Pt-SZ catalyst
      in the SPEEK/Pt-SZ self-humidifying membrane facilitated water balance and proton
      conduction, and accordingly improved its single cell performance under dry
      operation. In addition, the enhanced OCV and the decreased areal ohmic resistance
      confirmed the promotion effect of Pt-SZ catalyst in the self-humidifying membrane
      on suppressing reactant crossover and the membrane self-humidification.

PMID- 17521184
TI  - Enhanced silver ion binding to a rigid bisarene molecular cleft with formation of
      nonpolar pleated sheets through non-ionic intermolecular forces.
AB  - Silver ion complexation to bisarene ligands is enhanced by providing a
      conformationally rigid molecular cleft in the (Z)-acenaphthylene dimer 1. NMR
      titrations were used to determine complexation constants K for a series of
      ligands in tetrahydrofuran solution, with K = 4.9 M(-1) for the Z dimer 1 and 0.4
      M(-1) for the E dimer 2. Higher values of K were observed in CDCl(3)/CD(3)OD 9:1
      with K = 38 M(-1) for 1 and K = 4.1 M(-1) for 2. In the solid state, isolated
      clusters of [1 x (AgCF(3)SO(3))(2)](2) form a novel, pleated-sheet motif based on
      non-ionic interactions between clusters.

PMID- 17521185
TI  - Metal(II) hexafluorophosphates(V) (M = Sr, Pb) containing XeF(2)-coordinated
      metal ions [M(XeF(2))(3)](PF(6))(2), [Pb(3)(XeF(2))(11)](PF(6))(6), and
      [Sr(3)(XeF(2))(10)](PF(6))(6).
AB  - From the system MF(2)/PF(5)/XeF(2)/anhydrous hydrogen fluoride (aHF), four
      compounds [Sr(XeF(2))(3)](PF(6))(2), [Pb(XeF(2))(3)](PF(6))(2),
      [Sr(3)(XeF(2))(10)](PF(6))(6), and [Pb(3)(XeF(2))(11)](PF(6))(6) were isolated
      and characterized by Raman spectroscopy and X-ray single-crystal diffraction. The
      [M(XeF(2))(3)](PF(6))(2) (M = Sr, Pb) compounds are isostructural with the
      previously reported [Sr(XeF(2))(3)](AsF(6))(2). The structure of
      [Sr(3)(XeF(2))(10)](PF(6))(6) (space group C2/c; a = 11.778(6) Angstrom, b =
      12.497(6) Angstrom, c = 34.60(2) Angstrom, beta = 95.574(4) degrees, V = 5069(4)
      Angstrom(3), Z = 4) contains two crystallographically independent metal centers
      with a coordination number of 10 and rather unusual coordination spheres in the
      shape of tetracapped trigonal prisms. The bridging XeF(2) molecules and one
      bridging PF(6)- anion, which connect the metal centers, form complicated 3D
      structures. The structure of [Pb(3)(XeF(2))(11)](PF(6))(6) (space group C2/m; a =
      13.01(3) Angstrom, b = 11.437(4) Angstrom, c = 18.487(7) Angstrom, beta =
      104.374(9) degrees, V = 2665(6) Angstrom(3), Z = 2) consists of a 3D network of
      the general formula {[Pb(3)(XeF(2))(10)](PF(6))(6)}n and a noncoordinated XeF(2)
      molecule fixed in the crystal structure only by weak electrostatic interactions.
      This structure also contains two crystallographically independent Pb atoms. One
      of them possesses a unique homoleptic environment built up by eight F atoms from
      eight XeF(2) molecules in the shape of a cube, whereas the second Pb atom with a
      coordination number of 9 adopts the shape of a tricapped trigonal prism common
      for lead compounds. [Pb(3)(XeF(2))(11)](PF(6))(6) and
      [Sr(3)(XeF(2))(10)](PF(6))(6) are formed when an excess of XeF(2) is used during
      the process of the crystallization of [M(XeF(2))(3)](PF(6))(2) from their aHF
      solutions.

PMID- 17521186
TI  - Oxo-molybdenum(VI,V,IV) complexes of the facially coordinating
      tris(mercaptoimidazolyl)borate ligand: synthesis, characterization, and oxygen
      atom transfer reactivity.
AB  - A series of monooxo-Mo(IV,V) and dioxo-Mo(VI) complexes of the "soft" tripodal
      ligand, sodium tris(mercaptoimidazolyl)borate (NaTm(Me)), have been synthesized
      as potential oxygen atom transfer (OAT) models for sulfite oxidase. Complexes
      have been characterized by X-ray crystallography, cyclic voltammetry, and EPR,
      where appropriate. Oxygen atom transfer kinetics of Tm(Me)MoO(2)Cl, both
      stoichiometric and catalytic, have been studied by a combination of UV-vis and
      (31)P NMR spectroscopies under a variety of conditions. OAT rates are consistent
      with previously established relationships between redox potential/reactivity and
      mechanistic studies. The analysis of these complexes as potential structural and
      functional analogues of relevance to molybdoenzymes is further discussed.

PMID- 17521187
TI  - Interaction of plasmon and molecular resonances for rhodamine 6G adsorbed on
      silver nanoparticles.
AB  - Localized surface plasmon resonance (LSPR) is a key optical property of metallic
      nanoparticles. The peak position of the LSPR for noble-metal nanoparticles is
      highly dependent upon the refractive index of the surrounding media and has
      therefore been used for chemical and biological sensing. In this work, we explore
      the influence of resonant adsorbates on the LSPR of bare Ag nanoparticles
      (lambda(max,bare)). Specifically, we study the effect of rhodamine 6G (R6G)
      adsorption on the nanoparticle plasmon resonance because of its importance in
      single-molecule surface-enhanced Raman spectroscopy (SMSERS). Understanding the
      coupling between the R6G molecular resonances and the nanoparticle plasmon
      resonances will provide further insights into the role of LSPR and molecular
      resonance in SMSERS. By tuning lambda(max,bare) through the visible wavelength
      region, the wavelength-dependent LSPR response of the Ag nanoparticles to R6G
      binding was monitored. Furthermore, the electronic transitions of R6G on Ag
      surface were studied by measuring the surface absorption spectrum of R6G on an Ag
      film. Surprisingly, three LSPR shift maxima are found, whereas the R6G absorption
      spectrum shows only two absorption features. Deconvolution of the R6G surface
      absorption spectra at different R6G concentrations indicates that R6G forms
      dimers on the metal surface. An electromagnetic model based on quasi-static
      (Gans) theory reveals that the LSPR shift features are associated with the
      absorption of R6G monomer and dimers. Electronic structure calculations of R6G
      under various conditions were performed to study the origin of the LSPR shift
      features. These calculations support the view that the R6G dimer formation is the
      most plausible cause for the complicated LSPR response. These findings show the
      extreme sensitivity of LSPR in elucidating the detailed electronic structure of a
      resonant adsorbate.

PMID- 17521188
TI  - Experimental and theoretical examination of C-CN and C-H bond activations of
      acetonitrile using zerovalent nickel.
AB  - Experimental and density functional theory show that the reaction of acetonitrile
      with a zerovalent nickel bis(dialkylphosphino)ethane fragment (alkyl = methyl,
      isopropyl) proceeds via initial exothermic formation of an eta(2)-nitrile
      complex. Three well-defined transition states have been found on the potential
      energy surface between the eta(2)-nitrile complex and the activation products.
      The lowest energy transition state is an eta(3)-acetonitrile complex, which
      connects the eta(2)-nitrile to a higher energy eta(3)-acetonitrile intermediate
      with an agostic C-H bond, while the other two lead to cleavage of either the C-H
      or the C-CN bonds. Gas-phase calculations show C-CN bond activation to be
      endothermic, which contradicts the observation of thermal C-CN activation in THF.
      Therefore, the effect of solvent was taken into consideration by using the
      polarizable continuum model (PCM), whereupon the activation of the C-CN bond was
      found to be exothermic. Furthermore the C-CN bond activation was found to be
      favored exclusively over C-H bond activation due to the strong thermodynamic
      driving force and slightly lower kinetic barrier.

PMID- 17521189
TI  - Substituted diarylmethylamines by stereospecific intramolecular electrophilic
      arylation of lithiated ureas.

PMID- 17521190
TI  - Making "sense" of DNA.

PMID- 17521191
TI  - Computational insights into degenerate ethylene exchange with a Grubbs-type
      catalyst.

PMID- 17521192
TI  - A Pd(0)-catalyzed diamination of terminal olefins at allylic and homoallylic
      carbons via formal C-H activation under solvent-free conditions.

PMID- 17521194
TI  - Abyssomicin E, a highly functionalized polycyclic metabolite from Streptomyces
      species.
AB  - Abyssomicin E (1), a new polycyclic metabolite with a C19 skeleton, was isolated
      from Streptomyces sp. (HKI0381). Its chemical structure was determined by
      comprehensive NMR and MS spectroscopic analyses. For the first time in this
      recently discovered class of compounds, the absolute stereochemistry was directly
      established by subsequent single-crystal X-ray diffraction study using anomalous
      dispersion with copper radiation.

PMID- 17521195
TI  - Asymmetric reduction of beta-ketonitriles with a recombinant carbonyl reductase
      and enzymatic transformation to optically pure beta-hydroxy carboxylic acids.
AB  - Alpha-ethylation is concomitant with the reduction of aromatic beta-ketonitriles
      catalyzed by whole-cell biocatalysts. Use of isolated carbonyl reductase has
      completely eliminated this competing reaction. (R)-beta-Hydroxy nitriles were
      obtained via a reduction catalyzed by a recombinant carbonyl reductase with
      excellent optical purity and were further converted to (R)-beta-hydroxy
      carboxylic acids via a nitrilase-catalyzed hydrolysis. The present study allows
      ready access to both chiral beta-hydroxy nitriles and beta-hydroxy carboxylic
      acids of pharmaceutical importance.

PMID- 17521196
TI  - Efficient synthesis of 5-amido-3-hydroxy-4-pyrones as inhibitors of matrix
      metalloproteinases.
AB  - 3-hydroxy-4-pyrones are a class of important metal chelators with versatile
      medicinal applications. An efficient pathway for the preparation of new 5-amido-3
      hydroxy-4-pyrone derivatives has been developed. The synthesized 5-amido-3
      hydroxy-4-pyrones have been evaluated as inhibitors of matrix metalloproteinases.

PMID- 17521197
TI  - Crown ether vinylogous tetrathiafulvalene receptors: complexation interference on
      the molecular movements triggered by electron transfer.
AB  - The synthesis of a series of crown ether substituted vinylogous
      tetrathiafulvalenes (TTFVs) has been carried out through oxidative coupling of
      bisdithiafulvenes. These new receptors have been fully characterized using
      electrochemical, spectroelectrochemical, and molecular modeling experiments.
      These studies show that, upon oxidation, either a clip movement (TTFVs 3a,b) or a
      stretch movement (TTFV 3c) occurs, depending on the length of the crown ether
      chains. Preliminary electrochemical studies, undertaken on TTFV 3c in
      dichloromethane, show a little shift of the first standard oxidation potential
      toward more positive values upon addition of the Pb(2+) ion, but a considerable
      variation of the electron-transfer kinetics. This result introduces an
      interesting concept for the preparation of sensors not based on thermodynamic
      variations but on kinetic modifications of the electron transfer.

PMID- 17521198
TI  - The effect of the double bond pyramidalization on the mode of the bromination
      reaction: bromination of benzobicyclononadiene.
AB  - The bromination of 6,7,8,9-tetrahydro-5H-5,9-ethenobenzo[a][7]annulene yielded
      regio- and stereospecifically formed dibromides arising from the alkyl shift
      where the bromine exclusively attacks the double bond from the endo face of the
      double bond. DFT calculations on model compounds showed that the pyramidalization
      of the double bond and steric repulsion caused by the methylene protons are
      responsible for the stereo- and regioselective addition of bromine.

PMID- 17521199
TI  - A novel crystallization-induced diastereomeric transformation based on a
      reversible carbon-sulfur bond formation. Application to the synthesis of a gamma
      secretase inhibitor.
AB  - This paper describes a remarkably efficient process for the preparation of gamma
      secretase inhibitor 1. The target is synthesized in only five steps with an
      overall yield of 58%. The key operation is a highly selective and practical,
      crystallization-driven transformation for the conversion of a mixture of tertiary
      benzylic alcohols into the desired sulfide diastereomer with 94:6 dr. This
      unprecedented process is based upon a reversible carbon-sulfur bond formation
      under acidic conditions.

PMID- 17521200
TI  - Green analytical methodologies.

PMID- 17521201
TI  - Silicone nanocapsules templated inside the membranes of catanionic vesicles.
AB  - A simple and effective way to synthesize hollow silicone resin particles of
      controlled diameter is presented. The synthesis utilizes catanionic vesicles as
      templates for the polycondensation/polymerization processes of 1,3,5,7
      tetramethylcyclotetrasiloxane (D4H) within their membranes. Two different
      surfactant systems were used to form the vesicular templates: mixtures of
      dodecyltrimethylammonium bromide (DTAB) and sodium dodecylbenzenesulfonate (SDBS)
      in the cationic (the DTAB/SDBS system) or anionic (the SDBS/DTAB system) rich
      region of the phase diagram. The templates obtained from these surfactant
      mixtures form spontaneously unilamellar vesicles in aqueous solution. The
      vesicular templates swell upon addition of D4H, thus increasing their size. The
      silicone resin was obtained in acid- or base-catalyzed polycondensation and ring
      opening polymerization processes of D4H. In the case of the DTAB/SDBS system the
      formation of a densely cross-linked silicone material with SiO3/2 units allowed
      the nanocapsules to retain the vesicular shape after removal of the template,
      whereas in the SDBS/DTAB system, the polymer produces capsules which are too
      smooth to support surfactant lysis. The morphology of the silicone nanocapsules
      was analyzed using transmission electron microscopy (TEM) and, in some cases,
      atomic force microscopy (AFM). TEM and AFM reveal discrete hollow particles with
      a small amount of linked or aggregated hollow silica shells.

PMID- 17521202
TI  - Induction of instability in water-in-oil-in-water double emulsions by freeze-thaw
      cycling.
AB  - Individual water-in-oil-in-water (W1/O/W2) double-emulsion globules loaded with
      fluorescently labeled bovine serum albumin (FITC-BSA) were optically monitored
      within cylindrical capillaries during freeze-thaw cycling. Coalescence of
      internal aqueous droplets (W1) and external aqueous phase (W2), termed external
      coalescence, was not observed before or during freezing of the oil phase (O). On
      the other hand, this instability mechanism was readily promoted during thawing.
      This realization confirms the previously suggested potential of W1/O/W2 double
      emulsions to trigger release upon oil thawing and demonstrates that it is a
      direct result of globule breakage through external coalescence. The presented
      results also identified a threshold in the relative W1 droplet size above which
      instability occurred, while smaller droplets remained unperturbed and therefore
      indicate that optimization of the delivery can be achieved by tuning the size of
      W1 droplets. In addition, we propose a possible explanation for the occurrence of
      instability during oil thawing and its dependence on the size of W1 droplets.
      Because this alternative globule-breakage mechanism simply uses temperature
      increase (solid-to-liquid-phase transition) as external stimulus, W1/O/W2 double
      emulsion delivery systems can be easily tailored by choosing an oil phase with
      the appropriate phase-transition temperature.

PMID- 17521203
TI  - Electrooxidation of carbon monoxide and methanol on platinum-overlayer-coated
      gold nanoparticles: effects of film thickness.
AB  - The electrooxidation of carbon monoxide and methanol on Pt-coated Au
      nanoparticles attached to 3-aminopropyl trimethoxysilane-modified indium tin
      oxide electrodes was examined as a function of Pt film thickness and Au particle
      coverage. For the electrodes with medium and high Au particle coverages, the CO
      stripping peak position shifts to more negative values with increasing Pt film
      thickness, from ca. 0.8 V (vs Ag/AgCl) at 1 ML to 0.45 V at 10 ML. Accompanying
      this peak potential shift is the sharpening of the peak width from more than 150
      to 65 mV. For the electrode with low Au particle coverage, similar peak width
      narrowing was also observed, but the peak potential shift is much smaller, from
      0.85 V at 1 ML of Pt to 0.65 V at 10 ML. These observations are compared with the
      CO oxidation on bulk Pt electrodes and on Pt films deposited on bulk Au
      electrodes. The film-thickness-dependent CO oxidation is explained by d band
      theory in terms of strain and ligand effects, the particle size effect, and the
      particle aggregation induced by Pt film growth. Corresponding to the increasing
      CO oxidation activity, the current density of methanol oxidation grows with the
      Pt film thickness. The peak potential and current density reach the same values
      as those obtained on a polycrystalline bulk Pt electrode when more than 4 ML of
      Pt is deposited on the Au particle electrodes with a particle coverage higher
      than 0.25. These results suggest that it is feasible to reduce Pt loading in
      methanol fuel cells by using Pt thin films as the anode catalyst.

PMID- 17521204
TI  - Electrolyte-dependent pairwise particle motion near electrodes at frequencies
      below 1 kHz.
AB  - A model incorporating a phase angle between an applied electric field and the
      motion of particles driven by it explains electrolyte-dependent pairwise particle
      motion near electrodes. The model, predicting that two particles aggregate when
      this phase angle is greater than 90 degrees but separate when the phase angle is
      less than 90 degrees , was based largely on contrasting behavior in two
      electrolytes (KOH and NaHCO3) used with indium tin oxide (ITO) electrodes. The
      present contribution expands the experimental evidence for this model to KOH,
      NaHCO3, NaOH, NH4OH, KCl, and H2CO3 solutions with Pt, as well as ITO electrodes.
      The phase angle correlation was verified in all cases. Comparisons of the model
      predictions to experimental data show that the sign and order of magnitude of
      rates of change in the separation distances between particle pairs are correctly
      predicted.

PMID- 17521205
TI  - Aqueous dispersions of magnetite nanoparticles complexed with copolyether
      dispersants: experiments and theory.
AB  - Magnetite (Fe3O4) nanoparticles have been synthesized and complexed with
      carboxylate-functional block copolymers, and then aqueous dispersions of the
      complexes were investigated as functions of their chemical and morphological
      structures. The block copolymer dispersants had either poly(ethylene oxide),
      poly(ethylene oxide-co-propylene oxide), or poly(ethylene oxide-b-propylene
      oxide) outer blocks, and all of them had a polyurethane center block that
      contained pendent carboxylate groups. The complexes were formed through
      interactions of the carboxylates with the surfaces of the magnetite
      nanoparticles. The magnetite cores of the magnetite-copolymer complexes were near
      10 nm in diameter, and the particles were superparamagnetic. Complexes with mass
      ratios of polymer to magnetite varying from 50:50 to 85:15 were studied. One of
      our objectives is to design complexes that form stable dispersions of discrete
      particles in water, yet that can be actuated (moved together) upon exposure to a
      uniform magnetic field. DLVO calculations that accounted for magnetic attractive
      interparticle forces, as well as van der Waals, steric, and electrostatic forces
      are presented. Compositions were identified wherein a shallow, attractive
      interparticle potential minimum appears once the magnetic term is applied. This
      suggests that it may be possible to tune the structures of superparamagnetic
      nanoparticle shells to allow discrete dispersions without a field, yet weak
      flocculation could be induced upon exposure to a field.

PMID- 17521206
TI  - Surface-immobilized pyridine-functionalized gamma-cyclodextrin: alkanethiol co
      adsorption-induced reorientation.
AB  - Monolayers of di-6A,6B-deoxy-6-(4-pyridylmethyl)amino-gamma-cyclodextrin (gamma
      CD-(py)2) have been formed on polycrystalline platinum electrodes and
      investigated using electrochemical and surface-enhanced Raman spectroscopy
      (SERS). The behavior of self-assembled monolayers of (gamma-CD-(py)2) alone,
      (gamma-CD-(py)2) backfilled with 1-nonanethiol, and 1-nonanethiol are reported.
      The potential dependence of the capacitance indicates that the film capacitance
      is higher for the backfilled CD layers than for 1-nonanethiol layers, most likely
      due to ion flux through the CD cavity. SERS spectra of the backfilled layer
      exhibit features associated with both pyridine-functionalized CD and alkane
      moieties. Investigations using [Fe(CN)6]4- as a solution-phase probe indicate
      that the backfilled CD-alkane thiol layer exhibits enhanced blocking properties
      compared to gamma-CD-(py)2 films alone. Complete blocking was achieved by a
      combination of backfilling and insertion of a high-affinity guest 1
      adamantylamine into the cavity. Significantly, an electroactive guest with high
      affinity for gamma-CD, [Co(biptpy)2]2+, does not exhibit a redox response at the
      gamma-CD-(py)2 layer but molecular recognition is turned on by backfilling the CD
      layer with 1-nonanethiol molecules. This switching on of the electrochemical
      activity suggests that the CD hosts are initially inaccessible but reorientate
      upon backfilling, exposing the CD opening to solution and permitting a
      supramolecular host-guest complex to form. The binding of [Co(biptpy)2]2+ to
      gamma-CD in the backfilled monolayer depends on the bulk concentration of guest
      and is modeled by the Langmuir isotherm, yielding an association constant for the
      Co2+ state of 1.45 +/- 0.46 x 105 M-1 and a limiting surface coverage 1.49 +/-
      0.25 x 10-11 mol cm-2. The surface coverage of the divalent state is higher than
      the trivalent state, reflecting the dynamic nature of the inclusion.

PMID- 17521207
TI  - Phase separation of polymer-dispersed liquid crystals on a chemically patterned
      substrate.
AB  - The surface-induced structure formation of polymer-dispersed liquid crystals
      (PDLCs) on a chemically patterned substrate was studied for the first time. The
      patterns on the substrate were successfully transferred to the PDLC film,
      resulting in alternating LC-rich and polymer-rich phases. This simple approach
      offers a new means of organizing micrometer-sized LC domains into well-ordered
      structures in a polymer matrix of PDLCs.

PMID- 17521208
TI  - Thermodynamic Investigation of Staphylococcus epidermidis interactions with
      protein-coated substrata.
AB  - We evaluated self-assembled monolayers (SAMs) as potential coatings to prevent
      bacterial adhesion to biomaterials. Bacterial retention experiments were
      conducted on SAMs, some of which were coated with the model proteins fetal bovine
      serum (FBS) and fibronectin (FN). A thermodynamic approach was applied to
      calculate the Gibbs free energy changes of adhesion (DeltaG(adh)) of
      Staphylococcus epidermidis interacting with the substrates. When only nonspecific
      interactions controlled bacterial attachment, such as for the non-protein-coated
      substrates or the FBS substrates, the correlation between the thermodynamic
      predictions and measured values of bacterial retention was strong. However, when
      FN was adsorbed to the surfaces, the thermodynamic modeling underestimated
      bacterial adhesion, presumably since specific interactions between proteins of S.
      epidermidis and FN led to stronger attachment. Bacterial viability on the
      substrates was correlated with thermodynamic properties. For example, although
      bacteria attached more to surfaces having negative DeltaG(adh) values, these
      cells experienced the greatest loss of viability, presumably since strongly
      attached bacteria were unable to divide and grow. When the DeltaG(adh) values
      were decoupled into their components, we saw that acid-base interactions due to
      hydrogen bonding dominated the interactions of bacteria and proteins with each
      other and with the substrates in aqueous media. Finally, we discuss concerns
      regarding the use of the thermodynamic model to predict bacterial adhesion
      behavior in biomaterials systems.

PMID- 17521209
TI  - Adsorption and thermoresponsive behavior of poly(N-isopropylacrylamide-co-N,N'
      cystaminebisacrylamide) thin films on gold.
AB  - We describe the synthesis of thermoresponsive polymers made from N
      isopropylacrylamide and varying amounts of a thiol-containing co-monomer, N,N'
      cystaminebisacrylamide (P(NIPAm-co-CBAm)). Infrared spectroscopy revealed a
      backbone similar to that seen with pure PNIPAm. UV-vis spectroscopy showed that
      P(NIPAm-co-CBAm) undergoes a thermoresponsive phase transition around 32 degrees
      C in aqueous solution. The presence of the thiol groups enabled the polymer to
      adsorb onto gold surfaces. Following adsorption onto a gold surface, X-ray
      photoelectron spectroscopy showed a carbon/gold atomic ratio of 0.93 for a sample
      without CBAm and a ratio of 1.61 for a P(NIPAm-co-CBAm) sample with 0.20% CBAm.
      Quartz crystal microbalance (QCM) analysis showed increases in the mass of
      polymer adsorbed when the CBAm content in the polymer increased. The
      thermoresponsive behavior of the thin films on gold was investigated with contact
      angle and dissipative QCM analysis. Contact angles were measured for polymer
      films at both 25 and 60 degrees C. The largest temperature-induced alteration in
      the contact angle was seen with the 1.00% CBAm sample. Similarly, QCM-D results
      showed a significantly greater change in frequency and dissipation following a
      temperature change when CBAm was present than in pure NIPAm polymers.

PMID- 17521210
TI  - Tuning of metal work function with organic carboxylates and its application in
      top-emitting electroluminescent devices.
AB  - By fine-tuning of work functions and thus the hole-injection properties of Ag and
      Al anodes, an electroluminescent device was achieved by using various self
      assembled monolayers of organic carboxylate on the electrode surfaces. The IR
      spectra evidenced different binding behaviors of the carboxylates on Ag and Al. A
      correlation between the change in work function with the effective dipole moment
      along the surface normal and the currents in the hole-only devices was observed.
      These self-assembled-monolayer-modified metals were used as anodes in the
      fabrication of top-emitting organic light-emitting diodes (TOLEDs). The TOLED
      with the Ag anode modified by the perfluoroalkanoate exhibited a luminous
      efficiency as high as 18 cdA(-1), superior to that of the Ag2O-based device. With
      Al as the anode, the highest luminous efficiency was merely 6 cdA(-1) and decayed
      rapidly. The poorer EL property and performance of Al-based TOLEDs could be
      attributed to the weaker ionic bindings of carboxylates on Al and the weaker
      microcavity effect resulting from the inferior reflectivity of Al as compared to
      Ag.

PMID- 17521211
TI  - Magnetic properties of ZnO nanoparticles.
AB  - We experimentally show that it is possible to induce room-temperature
      ferromagnetic-like behavior in ZnO nanoparticles without doping with magnetic
      impurities but simply inducing an alteration of their electronic configuration.
      Capping ZnO nanoparticles ( approximately 10 nm size) with different organic
      molecules produces an alteration of their electronic configuration that depends
      on the particular molecule, as evidenced by photoluminescence and X-ray
      absorption spectroscopies and altering their magnetic properties that varies from
      diamagnetic to ferromagnetic-like behavior.

PMID- 17521212
TI  - Predictive study of charge transport in disordered semiconducting polymers.
AB  - We present a theoretical study of charge transport in disordered semiconducting
      polymers that relates the charge mobility to the chemical structure and the
      physical morphology in a novel multiscale approach. Our studies, focusing on
      poly(9,9-dioctylfluorene) (PFO), show that the charge mobility is dominated by
      pathways with the highest interchain charge-transfer rates. We also find that
      disorder is not always detrimental to charge transport. We find good agreement
      with experimental time-of-flight mobility data in highly aligned PFO films.

PMID- 17521213
TI  - Metabolic profile of nebivolol, a beta-adrenoceptor antagonist with unique
      characteristics.
AB  - beta-Adrenoceptor antagonists (beta-blockers) have historically been considered
      an effective and safe option for first-line treatment of hypertension. However,
      very recently, it has been proposed that beta-blockers should no longer be
      considered suitable for first-line therapy in the patient with uncomplicated
      hypertension because of unfavourable morbidity and mortality data. New evidence
      from recent clinical studies of nebivolol, a third-generation highly selective
      beta(1)-blocker with additional endothelial nitric oxide (NO)-mediated
      vasodilating activity, confirms previous findings that this drug differs from
      other beta-blockers. The combined mechanisms of beta-adrenoceptor antagonism and
      NO-mediated vasodilation may potentiate the blood pressure-lowering effect of
      this agent, and confer a broader favourable metabolic profile, which may be
      clinically relevant for hypertensive patients. The antioxidant properties of
      nebivolol and its neutral or even favourable effects on both carbohydrate and
      lipid metabolism are well documented. These properties consistently differentiate
      nebivolol from nonvasodilating beta-blockers such as atenolol, metoprolol or
      bisoprolol. Therapeutic indications for beta-blockers include a wide range of co
      morbidities found in hypertensive patients, including ischaemic heart disease,
      tachyarrhythmias and heart failure. Given that the majority of hypertensive
      patients require more than one drug to control blood pressure, the multiple
      mechanisms of action and favourable metabolic profile of nebivolol could make it
      an alternative therapeutic option for hypertensive patients requiring beta
      adrenoceptor therapy.

PMID- 17521214
TI  - Hormone-refractory prostate cancer: where are we going?
AB  - This article addresses the current status of therapeutic options in the
      management of hormone-refractory prostate cancer (HRPC). Following the
      publication of two landmark randomised trials, docetaxel chemotherapy is now the
      standard of care for men with metastatic HRPC. However, the benefit of this
      treatment is limited. Trials are now focusing on improving the efficacy of
      docetaxel by combining it with novel biological agents. Several new docetaxel
      based combinations are under evaluation and promising results have been found for
      the combination of docetaxel with angiogenesis inhibitors. Early phase III trial
      data for atrasentan appear interesting. New cytotoxic agents such as satraplatin
      and ixabepilone are being investigated in several ongoing studies in order to
      define their role as second-line treatments of HRPC. Vaccine therapy offers an
      active immunological approach for combating malignancy in a targeted manner.

PMID- 17521215
TI  - Epidermal growth factor receptor inhibitors in non-small cell lung cancer.
AB  - Aberrant epidermal growth factor receptor (EGFR) signalling contributes to
      neoplastic transformation and EGFR inhibition by antibodies and small molecules
      inhibits cancer cell proliferation and survival. In previously treated patients
      with non-small cell lung cancer, the administration of gefitinib and erlotinib
      are associated with objective tumour response rates of 8-19%. However, only
      erlotinib has been shown definitively to improve patient survival. The likelihood
      of benefit may be determined by the presence of specific genotypic abnormalities
      in EGFR or downstream pathway components. Additional evaluation to determine
      optimal dose/schedule of the agents combined with standard treatments and with
      other targeted agents in appropriately selected patients are areas of active
      research.

PMID- 17521216
TI  - Guidelines for the use of corticosteroids in the treatment of pulmonary
      sarcoidosis.
AB  - Sarcoidosis is the most common diffuse parenchymal lung disease and occurs
      worldwide. Although it affects all ethnic groups, prevalence and severity varies
      between different races. This has complicated the interpretation of existing
      clinical studies and extrapolation of their findings to different populations.
      Sarcoidosis can affect any organ, but the lungs are involved in >90% of patients,
      and respiratory specialists are therefore frequently responsible for their care.
      Oral corticosteroids have been used to treat sarcoidosis since the 1950s, with
      evidence of short- to medium-term improvement in symptoms, respiratory function
      and radiology. More recently, there have been studies examining the role of
      inhaled corticosteroids. The long-term benefits of corticosteroid treatment are
      nevertheless uncertain. Current international guidelines (published in 1999) on
      sarcoidosis, including recommendations on treatment, represent a consensus
      statement endorsed by North American and European respiratory societies. British
      guidelines on diffuse parenchymal lung disease, including sarcoidosis, were
      published in the same year. There are clearly areas where there is agreement and
      others where uncertainty persists. This article outlines current guidance with
      particular reference to which patients should be treated, when treatment should
      be commenced, the possible role of inhaled corticosteroids, how long treatment
      should be continued, and what monitoring should be performed for adverse events.

PMID- 17521217
TI  - Management options for malignant pleural mesothelioma: clinical and cost
      considerations.
AB  - Malignant pleural mesothelioma (MPM) is a resistant form of lung cancer that is
      often related to prior asbestos exposure. While surgical resection and
      radiotherapy techniques have been refined in recent years, neither has been
      proven to significantly extend patient survival compared with untreated controls.
      Until the release of pemetrexed in 2004, even combination chemotherapy regimens
      often resulted in a response rate of <20%. A recent phase III trial documented a
      41.3% response rate for cisplatin plus pemetrexed. In the future, new
      multimodality regimens featuring novel targeted therapies directed against
      molecular targets, such as the vascular endothelial growth factor, hold the
      greatest promise for improved outcomes in MPM. The standard radiographic
      assessment of response to MPM therapy remains a poor surrogate for clinically
      relevant endpoints such as median survival. Furthermore, it is not currently
      known whether aggressive multimodality treatment for MPM will improve survival or
      quality of life above and beyond symptomatic care. Ongoing clinical trials are
      comparing chemotherapy and surgery with supportive care in an effort to define
      the role of different therapies in MPM. MPM treatment is a costly public health
      issue; after efficacy is proven, additional studies are needed to measure the
      cost effectiveness of MPM treatment regimens.

PMID- 17521219
TI  - Ranibizumab.
AB  - Ranibizumab is the antigen-binding fragment of a recombinant, humanised
      monoclonal antibody, which binds with high affinity to, and inhibits the activity
      of, all active forms of vascular endothelial growth factor A, an important
      mediator in the development of choroidal neovascularisation. Well designed, phase
      III trials in patients with neovascular (wet) age-related macular degeneration
      (AMD) indicated that monthly intravitreal injections of ranibizumab 0.3 or 0.5 mg
      for up to 2 years maintained or improved visual acuity to a greater extent than
      sham injection, verteporfin photodynamic therapy or sham photodynamic therapy. In
      patients with predominantly classic wet AMD who received ranibizumab in
      combination with verteporfin therapy, preliminary results indicate that
      combination therapy is superior to that of verteporfin therapy alone. Most
      serious ocular adverse events, which were uncommon, were associated with either
      the injection procedure or ranibizumab.

PMID- 17521218
TI  - Immunosuppressive therapy and malignancy in organ transplant recipients: a
      systematic review.
AB  - Post-transplant malignancy is recognised as being a major limitation to the
      success of solid organ transplantation and it is currently considered one of the
      unavoidable costs of long-term immunosuppressive therapy. However, the continual
      introduction of new immunosuppressive drugs and the growing knowledge about their
      different oncogenic profiles, requires a continuous evaluation of the available
      evidence on this topic. The incidence and risk of malignancy is elevated in solid
      organ transplant recipients compared with the general population. As proof of the
      relationship between immunosuppressive therapy and post-transplant malignancy,
      epidemiological data reveal that the length of exposure to immunosuppressive
      therapy and the intensity of therapy are clearly related to the post-transplant
      risk of malignancy, and that once cancer has developed, more intense
      immunosuppression can translate into more aggressive tumour progression in terms
      of accelerated growth and metastasis and lower patient survival. The association
      between malignancy and immunosuppressive therapy is mediated through several
      pathogenic factors. Indirectly, immunosuppressive drugs greatly increase the post
      transplant risk of malignancy by impairing cancer surveillance and facilitating
      the action of oncogenic viruses. However, the direct pro- and anti-oncogenic
      actions of immunosuppressants also play an important role. The cancer-promoting
      effect of calcineurin inhibitors, independently of depressed immunosurveillance,
      has been demonstrated in recent years, and currently only mammalian target of
      rapamycin (mTOR) inhibitors have shown simultaneous immunosuppressive and
      antitumour properties. Reports of the initial results of the reduced incidence of
      cancer in organ transplant recipients receiving mTOR inhibitor therapy strongly
      indicate separate pathways for pharmacological immunosuppression and oncogenesis.
      The role of mTOR inhibitors has been firmly established for the treatment of post
      transplant Kaposi's sarcoma and its role in the management of patients with other
      post-transplant malignancies should be clarified as soon as possible. Prevention
      of morbidity and mortality resulting from post-transplant malignancy should
      become a main endpoint in solid organ transplant programmes, and the choice and
      management of immunosuppressive therapy in each phase of transplantation plays a
      central role in this objective. Although comprehensive and rigorous information
      about the management of immunosuppressive therapy in transplant recipients at
      risk of or affected by cancer is still lacking, new experimental and clinical
      data about mTOR inhibitors offers novel approaches to this problem.

PMID- 17521224
TI  - Long-acting formulations of atypical antipsychotics: time to reconsider when to
      introduce depot antipsychotics.
AB  - The current availability of a long-acting injectable formulation of risperidone
      and the potential future availability of long-acting formulations of other
      atypical antipsychotics (such as paliperidone) should prompt a reconsideration of
      at what stage in the treatment of schizophrenia such long-acting agents should be
      introduced. At present, long-acting formulations, particularly of conventional
      antipsychotics (depots), are usually reserved for patients with chronic
      schizophrenia who are at high-risk of noncompliance. Recent and increasing data
      from other patient groups, such as those with first-episode psychosis, suggest
      that long-acting risperidone is associated with good efficacy and tolerability
      leading to high patient acceptance, and treatment continuation rates that are
      greater than with oral antipsychotics. The benefits of an atypical antipsychotic
      coupled with the assurance of medication delivery in the form of a long-acting
      injection imply that these novel formulations should be considered in first
      episode patients, for whom optimal outcome is frequently compromised by early
      treatment discontinuation and poor adherence.

PMID- 17521223
TI  - Etanercept: a review of its use in the management of rheumatoid arthritis.
AB  - Etanercept (Enbrel), a soluble fusion protein that binds specifically to the
      cytokine human tumour necrosis factor (TNF), is approved for subcutaneous use in
      the treatment of patients with moderate to severe active rheumatoid arthritis,
      juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing arthritis and
      plaque psoriasis in the US, Italy, the rest of the EU and other countries
      worldwide. Subcutaneous etanercept was efficacious and generally well tolerated
      in several large, well designed, clinical trials and in the clinical-practice
      setting in adult patients with rheumatoid arthritis, including methotrexate-naive
      patients with early disease and those with long-standing, treatment-resistant
      active disease. Etanercept plus methotrexate combination therapy was generally
      superior to either monotherapy in reducing disease activity and structural joint
      damage, as well as improving health-related quality of life (HR-QOL).
      Furthermore, etanercept monotherapy was superior to placebo and at least as
      effective as methotrexate therapy in reducing disease activity and improving HR
      QOL in patients with early or refractory disease. The beneficial effects of
      etanercept monotherapy or combination therapy were sustained in the long term (<
      or =9 years). Some pharmaco-economic analyses suggest that etanercept is a cost
      effective option in the treatment of patients with rheumatoid arthritis. Direct
      head-to-head comparisons with other biological agents would help to definitively
      position etanercept with respect to these agents. Nevertheless, extensive
      clinical experience indicates that etanercept is a valuable treatment option in
      adult patients with long-standing moderate to severe active rheumatoid arthritis
      and an emerging option in those with early disease.

PMID- 17521225
TI  - Effect of HMG-CoA reductase inhibitors on beta-amyloid peptide levels:
      implications for Alzheimer's disease.
AB  - To date, a number of hypotheses of the cause of Alzheimer's disease, the most
      common form of dementia, have been postulated. The beta-amyloid peptide (Abeta)
      is the major constituent of senile plaques, which together with atrophy and
      neurofibrillary tangles, is the main neuropathological finding in Alzheimer's
      disease. It is a widely accepted theory that aggregation of Abeta into plaques is
      an initial event in the pathogenesis of Alzheimer's disease, driving
      neurodegeneration. The cholesterol hypothesis, primarily based on in vitro and
      animal studies, states that increased levels of cholesterol promote the
      production of Abeta. Furthermore, treating animals with HMG-CoA reductase
      inhibitors ('statins'; cholesterol-lowering agents), or adding these agents to
      cell culture, results in decreased production of Abeta. This 'positive' effect of
      statin treatment has further been verified by some, but not all, longitudinal
      studies where a reduced prevalence of Alzheimer's disease is seen among patients
      taking statins. These findings have together been interpreted to indicate that
      statins act via a cholesterol-dependent mechanism, reducing the production of
      Abeta and, hence, the risk of developing Alzheimer's disease. This review focuses
      on the cholesterol hypothesis of Alzheimer's disease and investigations into its
      validity in the clinical setting, i.e. the outcome of clinical trials where the
      effect of statin treatment on Abeta production has been studied. To date, the
      cholesterol hypothesis has not been shown to be valid in clinical trials. We
      hypothesise that the vascular contributions in Alzheimer's disease may be one
      possible mechanism for statins to interfere with the disease process and reduce
      the prevalence of Alzheimer's disease. We also suggest that statins may act
      through the inflammatory pathway. Both of these mechanistic suggestions are good
      candidates, supported by the literature, for the underlying mechanistic link
      between statin treatment and a reduced prevalence for Alzheimer's disease.

PMID- 17521226
TI  - Assessing the role of drugs in suicidal ideation and suicidality.
AB  - The emergence of suicidal ideation and suicide-related behaviour in patients
      receiving drug treatment is of concern because of the overall burden of these
      conditions and the possible link with completed suicide. Observational studies
      have been useful in generating hypotheses of causality but are confounded by the
      association between various disease states and increased suicide-related
      behaviour and completed suicide. The demonstration of causality requires
      experimental studies, especially randomised controlled trials, and meta-analyses.
      Unfortunately, the lack of uniform requirements for defining, detecting and
      recording suicidal ideation, suicide-related behaviour and completed suicide
      creates difficulties in comparing studies. Nevertheless, there is evidence of an
      association between SSRIs and other newer antidepressant drugs and treatment
      emergent suicidal ideation and suicide-related behaviour in both children and
      adults; however, an increase in completed suicide as a result of treatment with
      SSRIs and other newer antidepressant drugs has not been demonstrated. Atomoxetine
      has also been associated with treatment-emergent suicidality, based on the
      results of a meta-analysis. Although similar associations have been proposed for
      some antiepileptic drugs, isotretinoin and interferon-alpha, they are yet to be
      supported by evidence from randomised controlled trials or meta-analyses.

PMID- 17521227
TI  - Mood and anxiety disorders in patients with myasthenia gravis: aetiology,
      diagnosis and treatment.
AB  - Myasthenia gravis (MG) is a chronic, autoimmune disease involving neuromuscular
      junctions. It is frequently associated with symptoms such as loss of muscle
      strength, difficulty in respiration and swallowing, diplopia and ptosis. All
      chronic diseases, including MG, may have psychiatric consequences in terms of
      coping and adaptation. Psychiatric morbidity usually appears as anxiety
      disorders, such as panic disorder and generalised anxiety disorder, and as
      depressive disorders. However, there are very few data on the prevalence and
      aetiology of such psychiatric symptoms in patients with MG, and those available
      in the literature are generally from old studies with poor methodology. The
      interaction between MG and psychiatric disorders needs to be appreciated,
      especially in the primary care setting, since the symptoms may overlap. MG may be
      under-recognised initially because the psychiatric symptoms may coincide with
      those of the actual disease, such as fatigue, lack of energy and shortness of
      breath. On the other hand, co-morbid psychiatric symptoms that appear during the
      course of the illness may be misdiagnosed as true myasthenic symptoms; thus,
      leading to unnecessary drug treatment. Differentiation of the aetiology of these
      symptoms might alter the treatment choice and, therefore, affect the treatment
      success rate and patients' well-being. Psychiatric treatments must be carefully
      planned because of the risk of aggravating the underlying neurological disease.
      Even though there appears to be an intricate relationship between MG and
      psychiatric symptoms, there is very limited information on this subject. As such,
      prospective, randomised, controlled pharmaco/psychotherapy studies are needed to
      better direct the management of patients and, thus, improve quality of life
      during the course of the illness.

PMID- 17521228
TI  - Oral disease-modifying treatments for multiple sclerosis: the story so far.
AB  - Multiple sclerosis (MS) represents the prototypic inflammatory autoimmune
      disorder of the CNS. It is the most common cause of neurological disability in
      young adults and exhibits considerable clinical, radiological and pathological
      heterogeneity. Increased understanding of the immunopathological processes
      underlying this disease, advances in biotechnology and the development of
      powerful magnetic resonance imaging (MRI) technologies, together with
      improvements in clinical trial design, have led to a variety of valuable
      therapeutic approaches to MS. Therapy for MS has changed dramatically over the
      past decade, yielding significant progress in the treatment of relapsing
      remitting and secondary progressive forms; however, most of the clinically
      relevant therapeutic approaches are not yet available as oral formulations. A
      substantial number of preliminary and pivotal reports have provided promising
      results for oral therapies, and various phase III clinical trials are currently
      being initiated or are already underway evaluating the efficacy of a variety of
      orally administered agents, including cladribine, teriflunomide, laquinimod,
      fingolimod and fumaric acid. It is hoped that these trials will advance the
      development of oral therapies for MS.

PMID- 17521229
TI  - Impact of psychotropic medications on simulated driving: a critical review.
AB  - Driving a motor vehicle is central to the functional autonomy of patients with
      psychiatric illnesses. There have been many studies of the deleterious effects of
      psychotropic medications such as benzodiazepines, typical antipsychotics and
      tricyclic antidepressants (TCAs) on human motor skills; however, in the
      literature little attention has been paid to how such impairment affects driving
      ability. Computerised driving simulators offer a laboratory-based method of
      assessing the effects of specific psychotropic medications on driving abilities,
      in a standardised, controlled and safe manner. The purpose of the present article
      is to review research undertaken to-date on the effects of psychotropic
      medications on computer-simulated driving. A search of various databases,
      including MEDLINE, EMBASE and PsycInfo, was conducted. Forty-one articles
      assessing the impact of psychotropics on computer-simulated driving were
      identified. The pooled total number of subjects assessed in these simulator
      studies was 1336 (mean sample size 30.36 [SD 35.8]). The most common outcome
      measures in the various studies were speed, steering, deviation from lateral
      position (tracking, lane drifting), reaction time or braking accuracy, driving
      errors (e.g. errors in turning, coordination, gap acceptance, signalling,
      following distance) and vehicle collisions. The results of the studies were quite
      variable; however, the most common drug-related impairments included those of
      tracking and reaction time. Benzodiazepines and TCAs were most commonly
      associated with impairment, although the level of impairment was dependent on the
      population studied, the dose and the time of testing relative to drug
      administration. Computer-simulated driving provides a useful tool to research
      psychotropic-related impairment of driving abilities. Limitations of currently
      available data include the lack of generalisability, standardisation and small
      sample sizes.

PMID- 17521230
TI  - Selegiline transdermal system in major depressive disorder: profile report.

PMID- 17521232
TI  - Allogeneic transplantation and the risk for transmission of genetic disease: the
      heritable cancer disorders.
AB  - With the development of new approaches to transplantation therapy, such as those
      building upon the potential found in stem cells, it is vital to pursue a clear
      understanding of transplantation risks. Allogeneic transplantation presents risk
      for the transmission of disease of various types, including genetic disease.
      Predisposition to develop cancer is a feature of numerous genetic disorders, and
      it may be transmissible by transplantation. Some genetic disorders predisposing
      to cancer are remarkably common, either worldwide or in specific populations, and
      they could pose significant risk. Hence, to reduce risk to recipients, there is
      reason to exclude from donation those potential donors (including embryos)
      harboring certain germ-line mutations. However, the frequent absence of readily
      identifiable features might confound the effort to exclude those who harbor
      mutation. Thus, it is also important to consider the magnitude of risk that they
      represent. For some disorders, life-threatening cancer is highly likely to
      develop in those individuals born with germ-line mutation, but whether recipients
      would face the same risk from transplanted mutation is not always evident. Given
      the diversity of pathways that lead to cancer, there may be diverse factors that
      impact the likelihood for cancer to develop in the recipient, with some factors
      decreasing and others increasing the risk. One factor of special concern is the
      possibility that manipulation of donor cells, prior to transplantation, might
      introduce additional genetic or epigenetic abnormality, thereby increasing the
      risk.

PMID- 17521233
TI  - Embryonic stem cells.
AB  - Stem cells are unique cell populations with the ability to choose between self
      renewal and differentiation. Embryonic stem (ES) cells have the ability to form
      any fully differentiated cell of the body. To date, only three species of mammals
      have yielded long-term cultures of self-renewing ES cells- mice, monkeys, and
      humans. These cells have some special requirements to maintain their
      undifferentiated state in culture, e.g., presence of feeder cells, serum, or
      cytokines. Many scientific studies have tried to manipulate the growth and
      differentiation conditions with varied success. Studies of development in model
      systems, such as mice help our efforts to manipulate human stem cells in vitro.
      Data are now emerging that ES cells can be directed toward lineage-specific
      differentiation programs. On the basis of this property, it is likely that human
      ES cells will provide a useful differentiation culture system to study the
      mechanisms of human development. Recent advances in culturing ES cells and
      success in exploiting their pluripotency brings great hope for using human ES
      cell-based reparative therapy in future.

PMID- 17521234
TI  - Cell cycle differences in vitro between primitive hematopoietic cell populations
      from adult and umbilical cord blood.
AB  - Lineage-negative (Lin(-)) cell populations, obtained by negative selection from
      umbilical cord blood (UCB) and adult mobilized peripheral blood (aMPB), were
      cultured in serum-free liquid cultures supplemented with a mixture of seven
      stimulatory cytokines. On specific days, proliferation potential was assessed and
      cell cycle status was determined by DNA content. Expression of the cell cycle
      regulators cyclin D3 (cD3), cyclin-dependent kinase 4 (cdk4), p21(cip1/waf1)
      (p21), and p27(kip1) (p27) was also determined. As expected, UCB cells showed
      significantly higher proliferation potentials than aMPB cells, particularly
      during the first 7 days of culture. During this period of time, higher numbers of
      cell cycles were observed in UCB cells (7-9 cycles), as compared to aMPB cells (5
      6 cycles). Higher levels of cD3, cdk4, and p27 were also detected in UCB cells.
      Our results confirm that UCB cells possess an intrinsically higher proliferation
      potential, as compared to aMPB cells, and suggest that such a biological
      difference is due, at least in part, to differences in cell cycle status. This,
      in turn, seems to result from the differential expression of cell cycle
      regulatory molecules.

PMID- 17521235
TI  - Soluble signals from mechanically disrupted lung tissue induce lung-related gene
      expression in bone marrow-derived cells in vitro.
AB  - Differentiation of bone marrow (BM)-derived cells into lung epithelial cells has
      been reported in vivo in animal models of lung injury. Most studies have used
      cytokeratin or surfactant protein expression as markers of BM-to-lung cell
      differentiation. However, concerns as to whether fusion rather than
      differentiation is the mechanism involved, verification of BM-derived lung cells,
      and inconsistent findings with different injury models mean that the
      differentiation potential of BM-derived cells remains unclear. We used a co
      culture system, in which BM cell-lung cell fusion is prevented, to examine the
      ability of 'damage' signals released from mechanically disrupted lung tissue to
      induce expression of lung-related genes in BM-derived cells in vitro. BM-derived
      hematopoietic progenitor cells (BM-HPCs) were co-cultured with mechanically
      disrupted lung tissue. Liver tissue and medium-only co-cultures were also studied
      as controls. BM-HPCs differentiated into myeloid cells in culture. BM-HPCs
      proliferated in response to soluble lung damage signals and differentiated into
      suspension and adherent populations with dendritic cell and Langerhans cell-like
      characteristics, respectively. Cytokeratins 7 and 18 and surfactant protein B
      mRNA expression was either induced or upregulated in the dendritic cell (DC)-like
      population in lung co-cultures. In contrast, these genes were not induced or up
      regulated in medium only or liver co-cultures. Up-regulation of E-cadherin mRNA
      and protein expression also occurred in response to lung damage signals. These
      results confirm that signals released from damaged lung tissue can induce lung
      related gene expression in BM-derived DC-like cells in the absence of cell
      fusion.

PMID- 17521236
TI  - Effect of human thrombopoietin-modified bone marrow mesenchymal stem cells
      mediated by recombinant adeno-associated virus on megakaryocytopoiesis.
AB  - Recently, the research of recombinant thrombopoietin (TPO) and its subsequent use
      in treating thrombocytopenia following radiation therapy and chemotherapy have
      become more important in clinics. Our study was to determine the feasibility of
      recombinant adeno-associated virus (rAAV)-mediated TPO gene transfer into bone
      marrow-derived mesenchymal stem cells (MSCs) and to evaluate the conditioned
      medium (CM) obtained from TPO-transduced human (h) hMSCs for promoting the
      process of megakaryocytopoiesis. We constructed recombinant adeno-associated
      viruses expressing TPO successfully, and TPO mRNA and protein were both strongly
      expressed in TPO-transduced hMSCs. There was no decrease in green fluorescent
      protein (GFP) fluorescence expression of the transduced cells with continuous
      passaged culturing in vitro. The CM of TPO-transduced hMSCs has been shown to
      enhance the number of CD41(+) cells and megakaryocytic progenitors (colony
      forming unit-megakaryocyte) significantly as compared to the nontransduced
      control. In this study, a novel safe and efficient method of promoting the
      megakaryocytopoiesis was established following the TPO-transduced hMSCs. These
      results provide a basis for the future studies on hematopoietic regulation by
      hMSCs transfected with TPO.

PMID- 17521237
TI  - Epigenetic reprogramming of nonreplicating somatic cells for long-term
      proliferation by temporary cell-cell contact.
AB  - Embryonic stem (ES) cells are potential sources of tissue regeneration; however,
      transplanted ES cells produce tumors in the host tissues. In addition,
      transplantation between genetically unrelated individuals often results in graft
      rejection. Although the development of patient specific stem cell lines by
      somatic cell nuclear transfer (SCNT) represents a means of overcoming the problem
      of rejection, its human application has ethical dilemmas. Adult stem (AS) cells
      can also differentiate into specialized cells and may provide an alternative
      source of cells for human applications. In common with other somatic cells, AS
      cells have limited capacity for proliferation and cannot be produced in large
      quantities without genetic manipulation. We demonstrate here that nonreplicating
      mammalian cells can be reprogrammed for long-term proliferation by temporary cell
      cell contact through coculture of AS cells with the GM05267-derived F7 mouse cell
      line. Subsequent elimination of F7 cells from the co-culture allows proliferation
      of previously nonreplicating cells, colonies of which can be isolated to produce
      cell lines. We also demonstrate that the epigenetically reprogrammed AS cells,
      without the physical transfer of either nuclear or cytoplasmic material from
      other cells, are capable of long-term proliferation and able to relay signals to
      other nonreplicating cells to reinitiate proliferation with no addition of
      recombinant factors. The reported cell amplification procedure is
      methodologically simple and can be easily reproduced. This procedure allows the
      production of an unlimited number of cells from a limited number of AS cells,
      making them an ideal source of cells for applications involving autologous cell
      transplantation.

PMID- 17521238
TI  - Effective isolation and culture of endothelial cells in embryoid body
      differentiated from human embryonic stem cells.
AB  - We describe the isolation of endothelial cells from the center region of the
      attached embryoid body (EB) by a two-step enzyme treatment. The isolated cells
      from the center and outgrowth region of the EB were characterized separately. As
      human embryonic stem (hES) cells differentiated in EB, they lost expression of
      the undifferentiated marker Oct-4, whereas expression levels of endothelial
      specific markers were increased. Using RT-PCR, fluorescence-activated cell
      sorting (FACS) analysis, and immunofluorescence, we have shown that various
      endothelial cell markers, including platelet/endothelial cell adhesion molecule
      (PECAM), von Willebrand factor (vWF), Flk-1, and Tie2, were expressed on the
      attached EB. Compared with the outgrowth region of EB, the center region had a
      higher population of cells with these endothelial cell markers. Once isolated by
      the twostep enzyme treatment, cells from the center region continued to
      differentiate into endothelial cell lineage while expression level of endothelial
      cell markers in cells from the outgrowth region decreased in subcultures. This
      study has demonstrated that the isolation of EB by a two-step enzyme treatment is
      a useful technique to obtain endothelial cell marker-positive cells with high
      yield. Furthermore, a similar approach can be taken to identify the location and
      distribution of specific cell types in EB and thereby allow us to isolate and
      expand specific cell types.

PMID- 17521239
TI  - Phenotypic and functional analysis of human fetal liver hematopoietic stem cells
      in culture.
AB  - Steady-state hematopoiesis and hematopoietic transplantation rely on the unique
      potential of stem cells to undergo both self-renewal and multilineage
      differentiation. Fetal liver (FL) represents a promising alternative source of
      hematopoietic stem cells (HSCs), but limited by the total cell number obtained in
      a typical harvest. We reported that human FL nonobese diabetic/severe combined
      immunodeficient (NOD/SCID) repopulating cells (SRCs) could be expanded under
      simple stroma-free culture conditions. Here, we sought to further characterize FL
      HSC/SRCs phenotypically and functionally before and following culture. Unexpanded
      or cultured FL cell suspensions were separated into various subpopulations. These
      were tested for long-term culture potential and for in vivo repopulating function
      following transplantation into NOD/SCID mice. We found that upon culture of human
      FL cells, a tight association between classical stem cell phenotypes, such as
      CD34(+) /CD38(-) and/or side population, and NOD/SCID repopulating function was
      lost, as observed with other sources. Although SRC activity before and following
      culture consistently correlated with the presence of a CD34(+) cell population,
      we provide evidence that, contrary to umbilical cord blood and adult sources,
      stem cells present in both CD34(+) and CD34(-) FL populations can sustain long
      term hematopoietic cultures. Furthermore, upon additional culture, CD34-depleted
      cell suspensions, devoid of SRCs, regenerated a population of CD34(+) cells
      possessing SRC function. Our studies suggest that compared to neonatal and adult
      sources, the phenotypical characteristics of putative human FL HSCs may be less
      strictly defined, and reinforce the accumulated evidence that human FL represents
      a unique, valuable alternative and highly proliferative source of HSCs for
      clinical applications.

PMID- 17521240
TI  - CD34 modulates the trafficking behavior of hematopoietic cells in vivo.
AB  - The CD34 surface antigen has been recognized as a marker of hematopoietic stem
      cells (HSCs) and is widely used for HSC selection as well as for quality control
      in HSC transplantation. CD34 has been implicated in cytoadhesion signaling, and
      its expression has been suggested to reflect the activation state of
      hematopoietic progenitor cells. However, the function of CD34 remains essentially
      unknown. Here we analyzed the effects of ectopic CD34 expression in vivo in a
      bone marrow transplantation model. We transduced murine bone marrow stem cells
      with retroviral vectors encoding either murine full-length or the alternative
      splice product truncated CD34. Transduced cells were transplanted into syngeneic,
      marrow ablated hosts. For comparison, "control" animals received either enhanced
      green fluorescent protein (eGFP)-transduced or mock-transduced cells. Six months
      post-transplantation, transduced differentiated blood cells ectopically
      expressing murine CD34 showed decreased migration from peripheral blood to both
      bone marrow and thymus, an effect that was more pronounced with full-length CD34
      than with the truncated variant. In contrast, no influence of transgene
      expression on trafficking of differentiated blood cells was seen in the eGFP
      control group. Our data indicate that CD34 expression in mature blood cells has a
      suppressive effect on cellular trafficking to hematopoietic stroma organs,
      thereby supporting a modulating role of the CD34 molecule in cytoadhesion.

PMID- 17521241
TI  - Osteogenic differentiation of murine embryonic stem cells is mediated by
      fibroblast growth factor receptors.
AB  - The mechanisms involved in the control of embryonic stem (ES) cell
      differentiation are yet to be fully elucidated. However, it has become clear that
      the family of fibroblast growth factors (FGFs) are centrally involved. In this
      study we examined the role of the FGF receptors (FGFRs 1-4) during osteogenesis
      in murine ES cells. Single cells were obtained after the formation of embryoid
      bodies, cultured on gelatin-coated plates, and coaxed to differentiate along the
      osteogenic lineage. Upregulation of genes was analyzed at both the transcript and
      protein levels using gene array, relative-quantitative PCR (RQ-PCR), and Western
      blotting. Deposition of a mineralized matrix was evaluated with Alizarin Red
      staining. An FGFR1-specific antibody was generated and used to block FGFR1
      activity in mES cells during osteogenic differentiation. Upon induction of
      osteogenic differentiation in mES cells, all four FGFRs were clearly upregulated
      at both the transcript and protein levels with a number of genes known to be
      involved in osteogenic differentiation including bone morphogenetic proteins
      (BMPs), collagen I, and Runx2. Cells were also capable of depositing a
      mineralized matrix, confirming the commitment of these cells to the osteogenic
      lineage. When FGFR1 activity was blocked, a reduction in cell proliferation and a
      coincident upregulation of Runx2 with enhanced mineralization of cultures was
      observed. These results indicate that FGFRs play critical roles in cell
      recruitment and differentiation during the process of osteogenesis in mES cells.
      In particular, the data indicate that FGFR1 plays a pivotal role in osteoblast
      lineage determination.

PMID- 17521242
TI  - In vivo visualization and portally repeated transplantation of bone marrow cells
      in rats with liver damage.
AB  - Recent reports have raised concerns over the feasibility of differentiating bone
      marrow cells (BMCs) into functional hepatocytes. Such augmentation is considered
      necessary for potential clinical use of these cells in liver diseases. The
      present investigation was designed to determine the kinetics of transplanted BMCs
      and evaluate the effects of repeated bone marrow transplantation (BMT) in rat
      models of CCl(4)-induced liver damage. The early kinetics of transplanted BMCs
      was evaluated with a charge-coupled-device (CCD) camera using BMCs obtained from
      green fluorescent protein (GFP) transgenic (Tg) rats and followed up with in vivo
      imaging system (IVIS) using BMCs obtained from firefly luciferase (luc) Tg rats.
      We used a portal infusion system for repeated BMT. BMCs were transplanted via a
      peripheral vein or the portal vein (PV) once or repeatedly using this system. The
      results revealed that BMCs accumulated more in the damaged liver than in the
      intact liver. In the experimental group receiving repeated BMT via the PV, the
      liver fibrosis was milder than that in the group not receiving BMT, and large
      clusters of albumin-producing cells were detected by albumin staining. The
      injected BMCs were shown to accumulate in the damaged liver. This strategy of
      repeated BMT has potential clinical use in enhancing the number of albumin
      producing cells and suppressing liver fibrosis. This combination of beneficial
      effects may contribute to the benefits of cell transplantation therapy.
      Demonstration of the benefits of BMT in this study may be expected to have great
      significance for clinical trials.

PMID- 17521243
TI  - Mobilization of putative high-proliferative-potential endothelial colony-forming
      cells during antihypertensive treatment in patients with essential hypertension.
AB  - Recent studies have shown that in response to vascular damage or ischemia, bone
      marrow-derived endothelial progenitor cells (EPCs) are recruited into the
      circulation. To investigate whether antihypertensive treatment has an influence
      on the number of circulating EPCs, patients with essential hypertension were
      treated either with the angiotensin receptor antagonist telmisartan, the calcium
      channel blocker nisoldipine, or their combination for 6 weeks. At baseline and
      after 3 and 6 weeks of treatment, EPCs were identified and quantified by
      fluorescence-activated cell sorting (FACS) analysis and by their capacity to
      generate colony-forming units of the endothelial lineage (CFU-EC) in a
      methylcellulose-based assay. During treatment, patients in the nisoldipine
      groups, but not in the telmisartan group, showed a significant mobilization of
      EPCs, which in part had the capacity to generate large-sized colonies comprising
      more than 1,000 cells. Moreover, a remarkable correlation between the number of
      CFU-EC and the number of circulating CD133(+)/CD34(+)/CD146(+) cells was
      observed, thereby providing strong evidence that cells with this phenotype
      represent functional EPCs. No correlation was found between the numbers of CFU-EC
      and the blood pressure levels at any time point during the treatment. Hence,
      nisoldipine-induced mobilization of EPCs might represent a novel mechanism by
      which this antihypertensive compound independently of its blood pressure-lowering
      effect contributes to vasoprotection in patients with essential hypertension.

PMID- 17521244
TI  - Cryopreservation of rhesus macaque embryonic stem cells.
AB  - Studies using nonhuman primate embryonic stem (ES) cells will facilitate the
      translation of basic ES cell research to clinical use by providing a large animal
      model for in vivo testing. Unfortunately, nonhuman primate ES cells do not
      survive well following cryopreservation, a problem that limits the quantity and
      quality of these cells for research. More lines have to be established to fulfill
      demand, and thawed aliquots must go through more passages to generate adequate
      numbers. In addition, suboptimal cryopreservation can induce epigenetic changes
      and impose a selection bias for their outgrowth. Therefore, defining the optimal
      cryopreservation technique for nonhuman primate ES cells is critical for the
      further development of this research. To address this problem, we tested various
      cryoprotectants as well as cryopreservation procedures in an attempt to define a
      protocol that yields high viability with retention of ES cell phenotype and
      function. Here, we report a freezing protocol that preserves the intercellular
      attachments that are vital to primate ES cell function. We describe a slow,
      controlled-rate cooling protocol with ice crystal induction that increased the
      survival rate of ES cells from <22% to >90%. Preserved cells retained a normal
      karyotype and did not lose their ability to express markers of undifferentiated
      ES cells.

PMID- 17521246
TI  - Arthritis burden and impact are greater among U.S. women than men: intervention
      opportunities.
AB  - OBJECTIVES: To summarize arthritis burden and impact among women compared with
      men, using updated surveillance and impact measures; to describe public health
      approaches to arthritis; and to review effective, evidence-based arthritis self
      management interventions. RESULTS: Arthritis continues to burden the U.S.
      population as the leading cause of physical disability and affects women
      disproportionately: women with arthritis report greater prevalence of activity
      and work limitations, psychological distress, and severe joint pain than their
      male counterparts. Three main public health interventions can reduce arthritis
      impact: self-management education, physical activity, and weight management. Self
      management education programs are proven to reduce pain and depression, delay
      disability, improve self-efficacy, physical function, and quality of life, and
      reduce healthcare costs. Appropriate physical activity decreases pain, improves
      function, and delays disability. The American College of Rheumatology recommends
      maintaining a healthy weight to benefit patients with hip or knee osteoarthritis.
      Women appear more receptive to certain information delivery methods (i.e.,
      physician counseling) than men, suggesting gender-specific targeting of
      interventions may be of use. CONCLUSIONS: Effective interventions remain
      underused. The Centers for Disease Control and Prevention Arthritis Program and
      its partners, including state arthritis programs, continue their efforts to build
      the arthritis public health science base, monitor burden and impact, evaluate and
      disseminate evidence-based interventions, and work to decrease and delay
      disability, and increase quality of life among those with arthritis. As new
      approaches are developed, women and other disproportionately impacted groups
      merit particular consideration in tailoring and delivering programs to reduce
      arthritis burden.

PMID- 17521247
TI  - Recommendations to improve preconception health and health care: strategies for
      implementation.
AB  - Promoting preconception health and health care is widely accepted as a useful
      prevention strategy to lessen adverse maternal and infant health outcomes. There
      remains, however, a lack of national standards of practice or a comprehensive
      agenda to ensure that all women of childbearing age receive appropriate services
      that will enable them to achieve optimal health before any pregnancy. To address
      this need, the Centers for Disease Control and Prevention (CDC) launched the
      Preconception Health and Health Care Initiative, which aims to improve the health
      of women before pregnancy. In 2005, the CDC sponsored the first National Summit
      on Preconception Care, bringing together over 400 participants to share their
      expertise and information about various activities currently underway. In
      conjunction with the National Summit, a Select Panel on Preconception Care, a
      group of experts and representatives of 35 national organizations and 22 CDC
      programs, was convened. Based on the literature, presentations made at the
      National Summit, and deliberations during the Select Panel meeting, the
      recommendations to improve Preconception Health and Health Care--United States
      were developed. In order to move the recommendations from paper to practice, the
      Select Panel was convened to develop strategies to implement the recommendations
      across three areas: clinical practice, consumer roles, and public health
      practice. Future plans include developing a research agenda, supporting existing
      and new research activities, and developing policy and financing initiatives that
      will advance the practice of preconception health and health care. In addition, a
      Second National Summit is being planned. This paper describes current and future
      activities to implement the recommendations.

PMID- 17521248
TI  - Toward optimal health: Robert J. McConnell, M.D., discusses the clinical
      opportunities for improved thyroid disease management in women. Interview by Jodi
      R. Godfrey.

PMID- 17521249
TI  - Communicating with patients about extended-cycle and continuous use of oral
      contraceptives.
AB  - Oral contraceptives (OCs) have been the gold standard for contraception in the
      United States since their introduction in 1960. They are used for both their
      contraceptive and noncontraceptive benefits. Although the traditional dosing
      regimen, 21 active pills and 7 placebo pills, (21/7), reduces many symptoms women
      suffer with spontaneous cycles, hormone withdrawal symptoms often occur during
      the 7-day hormone-free interval. New contraceptives are available that decrease
      the number of hormone-free days each cycle or that increase the time between
      hormone-free intervals. These changes in packaging are expected to decrease the
      periodic hormone fluctuations experienced by OC users. Because routine use of
      extended-cycle/continuous OCs is relatively new and differs from what women have
      been told for years about the importance of monthly bleeding, women have many
      questions about and even significant reluctance to using these methods. Numerous
      studies have shown that extended-cycle and continuous OC use are safe and
      effective. Total bleeding episodes are reduced, as are problems with bloating and
      dysmenorrhea. Women usually experience more unscheduled spotting and bleeding in
      the initial cycles, but those problems decrease with longer use. Amenorrhea may
      be beneficial and suit the lifestyles of many women. Counseling women about all
      their contraceptive options and the variety of ways that OCs can be taken may
      increase women's commitment to correct use and increase efficacy. Good clinician
      patient communication, which includes creating an open dialogue with the patient
      to discuss her individual risks and benefits, should lead to more successful
      contraceptive utilization.

PMID- 17521250
TI  - Incidence and prevalence of intimate partner violence by and against women with
      severe mental illness.
AB  - Although a significant body of research has focused on the victimization of
      severely mentally ill persons and their perpetration of violence against others,
      relatively little attention has specifically addressed partner violence inflicted
      against and committed by severely mentally ill women. We conducted a review of
      the existing research to examine these issues. The published literature suggests
      that severely mentally ill women are at increased risk of being victimized by
      their partners and that a high proportion of severely mentally ill individuals
      may assault their intimate partners. Directions for future research and
      suggestions for clinical practice are presented.

PMID- 17521251
TI  - Phytoestrogens and coronary microvascular function in women with suspected
      myocardial ischemia: a report from the Women's Ischemia Syndrome Evaluation
      (WISE) Study.
AB  - AIMS: Soy phytoestrogens are popular, but information on their coronary effects
      in patients with suspected ischemic heart disease is limited. Accordingly, we
      investigated the relationship between blood phytoestrogen levels and coronary
      reactivity in women with suspected myocardial ischemia referred for coronary
      angiography. METHODS: Coronary flow velocity reserve (CFVR) and volumetric flow
      reserve (VFR) to adenosine (ADO) and nitroglycerin (NTG) (nonendothelial
      dependent responses) and acetylcholine (ACH) (endothelial-dependent response)
      were assessed in 106 women from the Women's Ischemia Syndrome Evaluation (WISE).
      Blood phytoestrogen (daidzein and genistein) and estrogen (estradiol) levels were
      correlated with coronary reactivity measures. RESULTS: Participants were mostly
      postmenopausal (79%), mean age 56 years, and 24% had obstructive coronary artery
      disease (CAD) at angiography. Genistein blood levels were negatively correlated
      with nonendothelial-dependent coronary flow responses. The highest genistein
      tertile (>6.1 ng/mL) had a CFVR of 2.1 +/- 0.5 (mean +/- SD) and VFRADO of 1.0 +/
      0.6, and both were significantly (p= 0.0001) lower compared with the other
      genistein tertiles combined. Similar associations were noted for CFVR(NTG) and
      VFR(NTG) (p = 0.03 and p = 0.01, respectively). The highest genistein tertile was
      associated with lower CFVR(ACH) compared with the other tertiles (p = 0.03). In
      multivariable modeling, blood genistein levels were significant independent
      predictors of coronary flow responses to ADO. There were no significant
      correlations between coronary reactivity variables and daidzein or endogenous
      estrogen. CONCLUSIONS: In women with suspected myocardial ischemia, higher
      genistein blood levels are associated with impaired nonendothelial-dependent and
      endothelial-dependent coronary microvascular function.

PMID- 17521252
TI  - Emergency contraception provision: a survey of Michigan physicians from five
      medical specialties.
AB  - OBJECTIVE: Despite the controversy over expanding delivery options for emergency
      contraceptive pills (ECP), little is known about physicians' attitudes toward
      over-the-counter (OTC) provision of ECP, and prior research on physicians'
      practices often has focused on a single specialty. This study examined the
      attitudes and practices regarding advance provision and OTC status of ECP among
      physicians in five medical specialties likely to encounter patients in need of
      ECP. METHODS: A mail survey of a random sample of 850 Michigan physicians in
      family/general medicine, internal medicine, obstetrics/gynecology, pediatrics,
      and emergency medicine was conducted. Respondents' ECP-related attitudes and
      practices were assessed, and differences by physician characteristics were
      examined using chi-square tests and multivariable logistic regression analyses.
      RESULTS: Two hundred seventy-one physicians responded to the survey (response
      rate = 32%), with 42% of them favoring OTC provision of ECP and 40% opposing it.
      Half of respondents never routinely initiated discussions about ECP with their
      sexually active, female patients, and 77% of respondents did not routinely offer
      advance prescriptions. After adjusting for other factors, including medical
      specialty, older physicians ( > or =50 years) were significantly more likely than
      their younger counterparts to support OTC provision of ECP (OR = 2.9, 95% CI 1.7
      4.9) or offer advance prescriptions (OR = 2.5, 95% CI 1.1-5.8). Physicians with a
      specialty in obstetrics/gynecology were 3.5 times (95% CI 1.3-9.8) as likely as
      physicians in family/general medicine to offer advance prescriptions for ECP, and
      female physicians were 2.5 (95% CI 1.05-6.0) times as likely as male physicians
      to offer advance prescriptions. Graduation from a medical school within the
      United States and practicing in a private practice were marginally associated
      with a lower likelihood of supporting OTC status of ECP (OR = 0.5, 95% CI: 0.2
      1.0; and OR equals; 0.6, 95% CI 0.3-1.1, respectively). CONCLUSIONS: Certain
      physician characteristics were significantly associated with their ECP-related
      attitudes and practices. The majority of physicians surveyed in this study did
      not offer advance prescriptions for ECP, and few had initiated discussions on ECP
      with patients, which may pose critical barriers to patients' timely access.

PMID- 17521253
TI  - Correlates of lesbian sexual functioning.
AB  - OBJECTIVE: The objectives of this descriptive study were (1) to characterize
      sexual functioning of lesbian women, (2) to validate the use of a modified
      version of the Female Sexual Function Index (FSFI) with lesbians, and (3) to
      evaluate correlates of sexual functioning in lesbians. METHODS: The current study
      was a cross-sectional examination of correlates of sexual functioning in lesbian
      women. Participants were 350 self-identified lesbians, aged > or = 18 (mean age
      35.5 +/- 11.4 years), who completed an anonymous, Internet-based survey. The
      survey instrument included measures of sociodemographics, sexual functioning,
      psychological symptoms, and relationship characteristics. RESULTS: Adequate
      reliability was demonstrated for all domains of the FSFI, as well as for the
      total score. Reliability coefficients were comparable to those obtained with the
      normative sample of heterosexual women. In univariate analyses, age,
      psychological symptoms, and relationship characteristics were related to many
      dimensions of sexual functioning in lesbians. Older age was associated with less
      desire for sexual activity, greater difficulty with lubrication during sexual
      activity, and lower scores for overall sexual functioning. Psychological symptoms
      were associated with decreased arousal, pleasure (i.e., orgasm), satisfaction,
      overall sexual functioning, and increased difficulty with lubrication during
      sexual activity. Higher relationship satisfaction was associated with increased
      arousal during sexual activity, less difficulty with lubrication during sexual
      activity, greater pleasure/orgasm, greater sexual satisfaction, and better
      overall sexual functioning. Psychological symptoms and relationship
      characteristics were consistently associated with aspects of sexual functioning
      in multivariate models. CONCLUSIONS: Age, psychological symptoms, and
      relationship characteristics were related to some but not all indices of female
      sexual functioning. Findings provide a solid empirical basis upon which to
      explore other determinants of sexual functioning in lesbians.

PMID- 17521254
TI  - Pregnancy intention and birth outcomes: does the relationship differ by age or
      race?
AB  - PURPOSE: We hypothesized that intended pregnancy is associated with decreased
      risk of poor birth outcomes, irrespective of age or race. METHODS: We conducted a
      cross-sectional study of 47,956 live singleton births using 1993-2001 data from
      the Centers for Disease Control and Prevention's (CDC) Pregnancy Risk Assessment
      Monitoring System (PRAMS). We used logistic regression to estimate the odds of
      giving birth to a very low birth weight/very preterm infant (VLBW/VPT) or an
      infant admitted to the neonatal intensive care unit (NICU) by pregnancy
      intention. RESULTS: Intended pregnancy was associated with a slightly higher risk
      than unintended pregnancy of a VLBW/VPT birth in young white women (< or = 22
      years) and black women of all ages. Intended pregnancy was associated with a
      slightly higher risk of infant NICU admission in white women under age 28 but
      with a lower or equivalent risk of infant NICU admission for black women of all
      ages than unintended pregnancy. From ages 22 to 37, black women had a
      significantly higher risk of VLBW/VPT birth with intended pregnancies than white
      women, but from ages 18 to 32, white women were at significantly more risk than
      black women of requiring infant NICU admission with intended pregnancies.
      CONCLUSIONS: Contrary to our hypothesis, an intended pregnancy at a young age was
      associated with a higher risk of poor birth outcomes.

PMID- 17521255
TI  - Family medicine physicians' advice about use of nonconventional modalities for
      menopausal symptom management.
AB  - AIMS: This study explores the beliefs and practices of family medicine physicians
      regarding the use of nonconventional modalities for menopausal symptom
      management. METHODS: Anonymous self-administered questionnaires were distributed
      to faculty and residents from eight participating family medicine residency
      programs around Florida, with an overall response rate of 66% (212 respondents).
      The survey explored what physicians report about patterns of patient inquiries
      and their responses to patients' inquiries about nonconventional modalities for
      specific menopausal symptoms and what physicians' report on their advice to
      patients about using specific herbs and supplements for menopausal symptom
      relief. RESULTS: Behavioral approaches were encouraged more than herbal
      therapies, acupuncture, and body therapies for the treatment of most of the
      menopausal symptoms. However, the most frequent response category was No advice.
      Resident physicians were significantly more likely than faculty to encourage
      acupuncture. Faculty physicians were more likely than residents to recommend
      particular herbal remedies. The majority of the respondents believed there was
      not sufficient evidence for recommending any of the herbs and supplements listed.
      CONCLUSIONS: These data reveal some important trends about how family medicine
      physicians respond to nontraditional approaches for menopausal symptom
      management. Because family medicine physicians typically receive some training in
      behavioral and psychotherapeutic approaches and there is some evidence for the
      effectiveness of behavioral strategies in menopausal symptom management, it is
      not surprising that they are more likely to endorse these approaches. Most family
      medicine physicians, however, have little or no training in the other
      nonconventional modalities, and our data show that these modalities received
      lower levels of endorsement, suggesting that physicians are not clear on their
      advantages or disadvantages.

PMID- 17521256
TI  - Breast, colorectal, and skin cancer screening practices and family history of
      cancer in U.S. women.
AB  - BACKGROUND: Several national medical organizations recommend more intensive
      screening or screening at an earlier age for individuals with a family history of
      breast, colorectal, or skin cancer. This study examined whether women with a
      family history of cancer were more likely to use breast, colorectal, or skin
      cancer screenings compared with those without such a family history. METHODS: The
      data for this study came from female respondents who participated in the 2000
      National Health Interview Survey. The age range of the study subjects and the
      definitions of cancer screening were determined based on the American Cancer
      Society recommendations on cancer screening. RESULTS: When compared with women
      without a family history of breast cancer, women with a family history were more
      likely to undergo a screening mammogram. Women who had a family history of
      colorectal cancer were twice as likely to use colorectal cancer screening than
      women without a family history of colorectal cancer. The association of family
      history with colorectal and breast cancer screening was stronger among the
      younger age group for which a screening test is recommended if one has such a
      family history. The association between skin cancer screening and family history
      of skin cancer was significant only in younger women. CONCLUSIONS: Women with a
      family history of cancer were more likely to have colorectal, breast, and skin
      cancer screening examinations. This may be a result of more physicians'
      recommendations and higher personal motivation for getting cancer screening,
      suggesting that the efficacy of national guidelines has been increasing somewhat.

PMID- 17521257
TI  - Depressive symptoms and indicators of maternal health status during pregnancy.
AB  - OBJECTIVES: Depressive symptoms are common among women, especially those who are
      of childbearing age or are pregnant. Prior studies have suggested that an
      increased burden of depressive symptoms is associated with diminished health and
      functional status, but these studies were primarily of middle-aged and older
      adults. In the current study, we investigated the relationship between depressive
      symptoms and health and functional status among pregnant women. METHODS: Women
      were enrolled in the study at their first prenatal visit to hospital-based
      clinics and administered an interview that contained the Center for Epidemiologic
      Studies Depression Scale (CES-D) to assess depressive symptoms and several
      questions to measure overall health status, limitations in performing moderate
      activities, and limitations in climbing stairs. RESULTS: The sample included 1163
      women. Women with higher levels of depressive symptoms, using cutoff points on
      the CES-D of either > or =16 (clinically significant) or > or =23 (major
      depression), had approximately twice the risk of poorer self-reported health and
      functional status than those with lower scores after adjustment for age, marital
      status, smoking, education, insurance, trimester, and race. CONCLUSIONS: These
      results suggest that an increased burden of depressive symptoms during pregnancy
      is associated with diminished health status and may offer an explanation for the
      reported association between depressive symptoms and preterm birth.

PMID- 17521258
TI  - What women want from their physicians: a qualitative analysis.
AB  - BACKGROUND: Despite increased efforts to improve the education of trainees in
      women's health, little information exists about what women want from their
      healthcare providers. Existing information from studies focuses on patient care
      and medical knowledge rather than on all six competencies mandated by the
      Accreditation Council of Graduate Medical Education (ACGME). OBJECTIVES: To
      identify what adult female patients want their physicians to know and be able to
      do in all ACGME competency areas in order to guide development of graduate
      women's health curricula. METHODS: We conducted two focus groups with 18
      volunteer adult female patients and one focus group with 5 community advocates.
      Questions addressed all six competency areas. The same female researcher
      moderated all three sessions. Two researchers analyzed session transcriptions for
      themes. RESULTS: Female patients and community advocates consistently stressed
      the need for their physicians to be able to navigate the healthcare system and to
      be their advocates. They also noted the need for physicians skilled in working
      with patients from a variety of cultures and for developing and maintaining
      respectful doctor-patient relationships, including good interpersonal
      communication. CONCLUSIONS: Patients' expectations of physicians extend beyond
      medical knowledge and patient care into the areas of communication, systems-based
      practice, and professionalism. Curricular changes in women's health at the
      postgraduate level should emphasize skills in these competencies, and needs
      assessment processes would do well to include patient viewpoints in the future.

PMID- 17521259
TI  - Treating pregnant women with antidepressants: the gray zone.

PMID- 17521265
TI  - Touched by suicide: bridging the perspectives of survivors and clinicians.
AB  - This article is a revised version of an invited plenary address given at the 39th
      Annual Conference of the American Association of Suicidology. The authors, a
      psychiatrist and a writer survivor, outline and summarize the different ways in
      which professionals and survivors come to an understanding of suicide. They
      explain how each group often exists independently and separate from the other--by
      cognitive and emotional dissonance, by private language, by psychological
      defenses and miscommunication--and call for dialog. They argue that both
      perspectives are essential to advance the science of suicidology and to give hope
      and meaning to those bereaved by suicide.

PMID- 17521266
TI  - The effects of preparedness for suicide following the death of a young adult
      child.
AB  - Suicide deaths are often viewed as sudden and unexpected. Research examining
      bereavement responses to suicide are generally set within this conceptual
      framework. Twenty-two parents were interviewed about their bereavement experience
      following the suicide death of a young adult son or daughter. Data analyzed using
      narrative methods revealed the concept of preparedness. Three distinct
      preparedness narratives were identified, termed turbulent-relief, tragedy, and
      reflective plots. The data presented here highlights the way in which these
      different situations influence the resultant grief. Understanding preparedness
      for suicide assists in explaining the variety of grief responses in parents
      bereaved in this manner.

PMID- 17521267
TI  - Control-group study of an intervention training program for youth suicide
      prevention.
AB  - Few studies have examined whether training can improve competency in intervening
      with suicidal youths. In this study we attempted to verify the effectiveness of
      such a training program on helper competency. Forty-three helpers who received
      the training were compared with 28 helpers who did not. Participants who received
      the training improved in knowledge, attitudes, and intervention skills following
      the training, compared with the control group across measures. Their gains were
      maintained at 6-month follow-up. In this sample, implementation of a one-time
      training program improved helpers' competencies in youth suicide intervention.

PMID- 17521268
TI  - Maintained attitudinal changes in nursing personnel after a brief training on
      suicide prevention.
AB  - Nursing personnel (N = 317) working at a general hospital attended a 6-hour
      training program on suicide prevention. They answered anonymously pre- and post
      training the Suicide Behavior Attitude Questionnaire (SBAQ), which comprises 21
      visual analogue scale items divided in three factorial subscales. The results
      indicated there were positive changes in the attitudes and these gains were
      significantly maintained at the 6-month follow-up evaluation. Improvement was in
      the Feelings and Professional Capacity subscales (ANOVA; p = 0.0001 and 0.01,
      respectively). There was no change on the Right to Suicide subscale. Because
      attitudes influence the effectiveness of health care personnel interventions, our
      findings may have important implications for the development of suicide
      prevention programs.

PMID- 17521269
TI  - Evidence-based practices project for suicide prevention.
AB  - Suicide continues to be a serious public health problem. In response to this
      problem, a myriad of suicide prevention programs have been developed and employed
      across the United States. Unfortunately, the effectiveness of many of these
      programs is unknown because they have not been evaluated using rigorous methods.
      The Evidence-Based Practices Project (EBPP) for suicide prevention was created in
      2002 to identify and promote evidence-based suicide prevention programs. In this
      paper the process and outcomes of the initial EBPP project within the context of
      the broader evidence-based movement are described, and the EBPPs creation of a
      best practice registry for suicide prevention is previewed.

PMID- 17521270
TI  - Suicide acceptability is related to suicide planning in U.S. adolescents and
      young adults.
AB  - The association between adolescents' and young adults' attitudes toward suicide
      and their own suicidality across five racial-ethnic classifications was studied
      in a nationally representative sample of 3,301 youth ages 14 to 22 years from the
      National Annenberg Risk Survey of Youth. Results indicate that adolescents and
      young adults who most strongly believe that it is acceptable to end one's life
      are more than fourteen times more likely to make a plan to kill themselves as
      those who do not have such beliefs (p < .001). Future behavioral prevention and
      intervention research should take into consideration adolescents' and young
      adults' approval of suicide as a risk factor for taking their own lives.

PMID- 17521271
TI  - Utah youth suicide study: barriers to mental health treatment for adolescents.
AB  - Forty-nine suicide cases were drawn from an original sample of 151 consecutive
      youth suicide deaths. We used information from 270 interviews with parents and
      other survivors to evaluate mental health treatment sought for and by the
      decedent and barriers to mental health treatment. Participants reported the same
      primary barriers for the decedent: belief that nothing could help, seeking help
      is a sign of weakness or failure, reluctance to admit to having mental health
      problems, denial of problems, and too embarrassed to seek help. It is suggested
      that the stigma of mental illness is a considerable barrier to mental health
      treatment.

PMID- 17521272
TI  - Multiple pathways from stress to suicidality and the protective effect of social
      support in Hong Kong adolescents.
AB  - Two theoretical models were constructed to illustrate how stressful events,
      family and friends support, depression, substance use, and death attitude
      mutually influence to create cumulative risks for suicide. The models were
      evaluated using structural equation modeling. Results showed that suicidality was
      strongly predicted by death attitude, depression, and substance use which
      together form a dangerous combination of risk factors at the personal level.
      Within the adolescent's social environment, stressful events increased
      suicidality through intensifying depression, substance use, and death acceptance,
      whereas family and friends support lowered it, partly through reducing stress and
      death acceptance. The effect (direct and indirect combined) of family support was
      much stronger than that of friends support. Enhancing stress coping ability,
      promoting positive family relationships, and attacking attitudes supportive of
      death might be the best strategies to prevent youth suicide.

PMID- 17521273
TI  - Ethnocultural aspects of suicide in young people: a systematic literature review
      part 1: Rates and methods of youth suicide.
AB  - The study of ethnocultural aspects of suicidal behaviour is, at the moment, still
      a neglected area. The relatively few studies available are mainly on adults;
      young people usually are not examined separately. The authors reviewed 82
      publications on youth suicide that have addressed, to different degrees, the
      ethnicity/culture of the population studied. Following a description of the main
      characteristics shared by these researches (e.g., predominance of studies on
      Blacks, Whites, and Hispanics; lack of qualitative methodology, etc.), the rates
      and methods of youth suicide, from a cross-cultural perspective are discussed.

PMID- 17521274
TI  - Ethnocultural aspects of suicide in young people: a systematic literature review
      part 2: Risk factors, precipitating agents, and attitudes toward suicide.
AB  - Different scholars have expressed the same regret for the lack of research on
      ethnocultural differences in youth suicide behavior and the need to conduct more
      comparative studies, necessary to develop culturally responsive prevention and
      intervention strategies. The authors reviewed 82 publications on youth suicide
      that have considered, to different degrees, the ethnicity/culture of the
      population studied. Part 1 of this article explored youth suicide rates and
      methods (SLTB, this issue), while the present paper examines risk and
      precipitating factors and attitudes toward suicide in young people from a cross
      cultural perspective.

PMID- 17521275
TI  - Self-mutilation and coping strategies in a college sample.
AB  - The goal of this study was to examine the use of specific coping strategies among
      self-mutilating college students. The self-mutilating group (n = 44) reported
      utilizing avoidance strategies more often than did a control group (n = 44)
      matched for general psychological distress but with no history of self
      mutilation. In addition, female, but not male, self-mutilators endorsed using
      problem-solving and social support seeking strategies less often than
      nonmutilators. These findings suggest that coping strategies in general and
      avoidance-based strategies in particular may be important targets for the
      treatment of self-mutilative behaviors.

PMID- 17521276
TI  - Estimating information rates with confidence intervals in neural spike trains.
AB  - Information theory provides a natural set of statistics to quantify the amount of
      knowledge a neuron conveys about a stimulus. A related work (Kennel, Shlens,
      Abarbanel, & Chichilnisky, 2005) demonstrated how to reliably estimate, with a
      Bayesian confidence interval, the entropy rate from a discrete, observed time
      series. We extend this method to measure the rate of novel information that a
      neural spike train encodes about a stimulus--the average and specific mutual
      information rates. Our estimator makes few assumptions about the underlying
      neural dynamics, shows excellent performance in experimentally relevant regimes,
      and uniquely provides confidence intervals bounding the range of information
      rates compatible with the observed spike train. We validate this estimator with
      simulations of spike trains and highlight how stimulus parameters affect its
      convergence in bias and variance. Finally, we apply these ideas to a recording
      from a guinea pig retinal ganglion cell and compare results to a simple linear
      decoder.

PMID- 17521277
TI  - Generation of synthetic spike trains with defined pairwise correlations.
AB  - Recent technological advances as well as progress in theoretical understanding of
      neural systems have created a need for synthetic spike trains with controlled
      mean rate and pairwise cross-correlation. This report introduces and analyzes a
      novel algorithm for the generation of discretized spike trains with arbitrary
      mean rates and controlled cross correlation. Pairs of spike trains with any
      pairwise correlation can be generated, and higher-order correlations are
      compatible with common synaptic input. Relations between allowable mean rates and
      correlations within a population are discussed. The algorithm is highly
      efficient, its complexity increasing linearly with the number of spike trains
      generated and therefore inversely with the number of cross-correlated pairs.

PMID- 17521278
TI  - Input-driven oscillations in networks with excitatory and inhibitory neurons with
      dynamic synapses.
AB  - Previous work has shown that networks of neurons with two coupled layers of
      excitatory and inhibitory neurons can reveal oscillatory activity. For example,
      Borgers and Kopell (2003) have shown that oscillations occur when the excitatory
      neurons receive a sufficiently large input. A constant drive to the excitatory
      neurons is sufficient for oscillatory activity. Other studies (Doiron, Chacron,
      Maler, Longtin, & Bastian, 2003; Doiron, Lindner, Longtin, Maler, & Bastian,
      2004) have shown that networks of neurons with two coupled layers of excitatory
      and inhibitory neurons reveal oscillatory activity only if the excitatory neurons
      receive correlated input, regardless of the amount of excitatory input. In this
      study, we show that these apparently contradictory results can be explained by
      the behavior of a single model operating in different regimes of parameter space.
      Moreover, we show that adding dynamic synapses in the inhibitory feedback loop
      provides a robust network behavior over a broad range of stimulus intensities,
      contrary to that of previous models. A remarkable property of the introduction of
      dynamic synapses is that the activity of the network reveals synchronized
      oscillatory components in the case of correlated input, but also reflects the
      temporal behavior of the input signal to the excitatory neurons. This allows the
      network to encode both the temporal characteristics of the input and the presence
      of spatial correlations in the input simultaneously.

PMID- 17521279
TI  - Extracting number-selective responses from coherent oscillations in a computer
      model.
AB  - Cortical neurons selective for numerosity may underlie an innate number sense in
      both animals and humans. We hypothesize that the number- selective responses of
      cortical neurons may in part be extracted from coherent, object-specific
      oscillations . Here, indirect evidence for this hypothesis is obtained by
      analyzing the numerosity information encoded by coherent oscillations in
      artificially generated spikes trains. Several experiments report that gamma-band
      oscillations evoked by the same object remain coherent, whereas oscillations
      evoked by separate objects are uncorrelated. Because the oscillations arising
      from separate objects would add in random phase to the total power summed across
      all stimulated neurons, we postulated that the total gamma activity, normalized
      by the number of spikes, should fall roughly as the square root of the number of
      objects in the scene, thereby implicitly encoding numerosity. To test the
      hypothesis, we examined the normalized gamma activity in multiunit spike trains,
      50 to 1000 msec in duration, produced by a model feedback circuit previously
      shown to generate realistic coherent oscillations. In response to images
      containing different numbers of objects, regardless of their shape, size, or
      shading, the normalized gamma activity followed a square-root-of-n rule as long
      as the separation between objects was sufficiently large and their relative size
      and contrast differences were not too great. Arrays of winner-take-all numerosity
      detectors, each responding to normalized gamma activity within a particular band,
      exhibited tuning curves consistent with behavioral data. We conclude that
      coherent oscillations in principle could contribute to the number-selective
      responses of cortical neurons, although many critical issues await experimental
      resolution.

PMID- 17521280
TI  - Selectivity and stability via dendritic nonlinearity.
AB  - Inspired by recent studies regarding dendritic computation, we constructed a
      recurrent neural network model incorporating dendritic lateral inhibition. Our
      model consists of an input layer and a neuron layer that includes excitatory
      cells and an inhibitory cell; this inhibitory cell is activated by the pooled
      activities of all the excitatory cells, and it in turn inhibits each dendritic
      branch of the excitatory cells that receive excitations from the input layer.
      Dendritic nonlinear operation consisting of branch-specifically rectified
      inhibition and saturation is described by imposing nonlinear transfer functions
      before summation over the branches. In this model with sufficiently strong
      recurrent excitation, on transiently presenting a stimulus that has a high
      correlation with feed- forward connections of one of the excitatory cells, the
      corresponding cell becomes highly active, and the activity is sustained after the
      stimulus is turned off, whereas all the other excitatory cells continue to have
      low activities. But on transiently presenting a stimulus that does not have high
      correlations with feedforward connections of any of the excitatory cells, all the
      excitatory cells continue to have low activities. Interestingly, such stimulus
      selective sustained response is preserved for a wide range of stimulus intensity.
      We derive an analytical formulation of the model in the limit where individual
      excitatory cells have an infinite number of dendritic branches and prove the
      existence of an equilibrium point corresponding to such a balanced low-level
      activity state as observed in the simulations, whose stability depends solely on
      the signal-to-noise ratio of the stimulus. We propose this model as a model of
      stimulus selectivity equipped with self-sustainability and intensity-invariance
      simultaneously, which was difficult in the conventional competitive neural
      networks with a similar degree of complexity in their network architecture. We
      discuss the biological relevance of the model in a general framework of
      computational neuroscience.

PMID- 17521281
TI  - Filtering of spatial bias and noise inputs by spatially structured neural
      networks.
AB  - With spatially organized neural networks, we examined how bias and noise inputs
      with spatial structure result in different network states such as bumps,
      localized oscillations, global oscillations, and localized synchronous firing
      that may be relevant to, for example, orientation selectivity. To this end, we
      used networks of McCulloch-Pitts neurons, which allow theoretical predictions,
      and verified the obtained results with numerical simulations. Spatial inputs, no
      matter whether they are bias inputs or shared noise inputs, affect only firing
      activities with resonant spatial frequency. The component of noise that is
      independent for different neurons increases the linearity of the neural system
      and gives rise to less spatial mode mixing and less bistability of population
      activities.

PMID- 17521282
TI  - Imposing biological constraints onto an abstract neocortical attractor network
      model.
AB  - In this letter, we study an abstract model of neocortex based on its
      modularization into mini- and hypercolumns. We discuss a full-scale instance of
      this model and connect its network properties to the underlying biological
      properties of neurons in cortex. In particular, we discuss how the biological
      constraints put on the network determine the network's performance in terms of
      storage capacity. We show that a network instantiating the model scales well
      given the biologically constrained parameters on activity and connectivity, which
      makes this network interesting also as an engineered system. In this model, the
      minicolumns are grouped into hypercolumns that can be active or quiescent, and
      the model predicts that only a few percent of the hypercolumns should be active
      at any one time. With this model, we show that at least 20 to 30 pyramidal
      neurons should be aggregated into a minicolumn and at least 50 to 60 minicolumns
      should be grouped into a hypercolumn in order to achieve high storage capacity.

PMID- 17521283
TI  - Combining reconstruction and discrimination with class-specific sparse coding.
AB  - Sparse coding is an important approach for the unsupervised learning of sensory
      features. In this contribution, we present two new methods that extend the
      traditional sparse coding approach with supervised components. Our goal is to
      increase the suitability of the learned features for classification tasks while
      keeping most of their general representation capability. We analyze the effect of
      the new methods using visualization on artificial data and discuss the results on
      two object test sets with regard to the properties of the found feature
      representation.

PMID- 17521284
TI  - SVDD-based pattern denoising.
AB  - The support vector data description (SVDD) is one of the best-known one-class
      support vector learning methods, in which one tries the strategy of using balls
      defined on the feature space in order to distinguish a set of normal data from
      all other possible abnormal objects. The major concern of this letter is to
      extend the main idea of SVDD to pattern denoising. Combining the geodesic
      projection to the spherical decision boundary resulting from the SVDD, together
      with solving the preimage problem, we propose a new method for pattern denoising.
      We first solve SVDD for the training data and then for each noisy test pattern,
      obtain its denoised feature by moving its feature vector along the geodesic on
      the manifold to the nearest decision boundary of the SVDD ball. Finally we find
      the location of the denoised pattern by obtaining the pre-image of the denoised
      feature. The applicability of the proposed method is illustrated by a number of
      toy and real-world data sets.

PMID- 17521285
TI  - Feature selection via coalitional game theory.
AB  - We present and study the contribution-selection algorithm (CSA), a novel
      algorithm for feature selection. The algorithm is based on the multiperturbation
      shapley analysis (MSA), a framework that relies on game theory to estimate
      usefulness. The algorithm iteratively estimates the usefulness of features and
      selects them accordingly, using either forward selection or backward elimination.
      It can optimize various performance measures over unseen data such as accuracy,
      balanced error rate, and area under receiver-operator-characteristic curve.
      Empirical comparison with several other existing feature selection methods shows
      that the backward elimination variant of CSA leads to the most accurate
      classification results on an array of data sets.

PMID- 17521286
TI  - Outliers detection in multivariate time series by independent component analysis.
AB  - In multivariate time series, outlying data may be often observed that do not fit
      the common pattern. Occurrences of outliers are unpredictable events that may
      severely distort the analysis of the multivariate time series. For instance,
      model building, seasonality assessment, and forecasting may be seriously affected
      by undetected outliers. The structure dependence of the multivariate time series
      gives rise to the well-known smearing and masking phenomena that prevent using
      most outliers' identification techniques. It may be noticed, however, that a
      convenient way for representing multiple outliers consists of superimposing a
      deterministic disturbance to a gaussian multivariate time series. Then outliers
      may be modeled as nongaussian time series components. Independent component
      analysis is a recently developed tool that is likely to be able to extract
      possible outlier patterns. In practice, independent component analysis may be
      used to analyze multivariate observable time series and separate regular and
      outlying unobservable components. In the factor models framework too, it is shown
      that independent component analysis is a useful tool for detection of outliers in
      multivariate time series. Some algorithms that perform independent component
      analysis are compared. It has been found that all algorithms are effective in
      detecting various types of outliers, such as patches, level shifts, and isolated
      outliers, even at the beginning or the end of the stretch of observations. Also,
      there is no appreciable difference in the ability of different algorithms to
      display the outlying observations pattern.

PMID- 17521287
TI  - The crystal structure of the pentahaem c-type cytochrome NrfB and
      characterization of its solution-state interaction with the pentahaem nitrite
      reductase NrfA.
AB  - NrfB is a small pentahaem electron-transfer protein widely involved in the
      respiratory reduction of nitrite or nitric oxide to ammonia, processes that
      provide energy for anaerobic metabolism in many enteric bacteria and also serve
      to detoxify these reactive nitrogen species. The X-ray crystal structure of
      Escherichia coli NrfB is presented at 1.74 A (1 A=0.1 nm) resolution. The
      architecture of the protein is that of a 40 A 'nanowire' in which the five haems
      are positioned within 6 A of each other along a polypeptide scaffold. During
      nitrite reduction, the physiological role of NrfB is to mediate electron transfer
      to another pentahaem protein, NrfA, the enzyme that catalyses periplasmic nitrite
      or nitric oxide reduction. Protein-protein interaction studies suggest NrfA and
      NrfB can form a 20-haem NrfA2-NrfB2 heterotetrameric complex.

PMID- 17521288
TI  - Regulation of p73-mediated apoptosis by c-Jun N-terminal kinase.
AB  - The JNK (c-Jun N-terminal kinase)/mitogen-activated protein kinase signalling
      pathway is a major mediator of stress responses in cells, including the response
      to DNA damage. DNA damage also causes the stabilization and activation of p73, a
      member of the p53 family of transcription factors. p73, like p53, can mediate
      apoptosis by up-regulating the expression of pro-apoptotic genes, including Bax
      (Bcl2-associated X protein) and PUMA (p53 up-regulated modulator of apoptosis).
      Changes in p73 expression have been linked to tumour progression, particularly in
      neuroblastomas, whereas in tumours that feature inactivated p53 there is evidence
      that p73 may mediate the apoptotic response to chemotherapeutic agents. In the
      present study, we demonstrate a novel link between the JNK signalling pathway and
      p73. We use pharmacological and genetic approaches to show that JNK is required
      for p73-mediated apoptosis induced by the DNA damaging agent cisplatin. JNK forms
      a complex with p73 and phosphorylates it at several serine and threonine
      residues. The mutation of JNK phosphorylation sites in p73 abrogates cisplatin
      induced stabilization of p73 protein, leading to a reduction in p73
      transcriptional activity and reduced p73-mediated apoptosis. Our results
      demonstrate that the JNK pathway is an important regulator of DNA damage-induced
      apoptosis mediated by p73.

PMID- 17521289
TI  - Collagen pretzels revealed by electron microscopy.
AB  - Collagen XV is a million-dalton protein with a structural role in skeletal muscle
      and capillaries. As with all collagens, studies of its function are hindered by
      the absence of good structural data: collagens are triple-helical, non
      crystallizable, multidomain proteins with extensive post-translational
      modification that are refractory to analysis by high-resolution structural
      techniques. For collagen XV, this situation is compounded by the fact that it is
      also a proteoglycan. In this issue of the Biochemical Journal, Myers and her
      colleagues use rotary shadowing electron microscopy to obtain images of purified
      collagen XV molecules that are sufficiently detailed to show the three-lobed
      structure of the N-terminus and individual glycosaminoglycan side chains.
      Individual molecules appear as knotted strands resembling a pretzel (a pastry
      snack folded in a unique figure-of-eight), which contrasts with our conventional
      image of collagen molecules as semi-rigid rods. Importantly, collagen XV
      multimerizes into cruciform structures in which simpler forms have two to four
      molecules per complex. Immunoelectron microscopy revealed knotted collagen XV
      complexes bridging collagen fibrils adjacent to basement membrane. These
      accomplishments are made all the more impressive by the fact that collagen XV was
      purified from human umbilical cord, in which the protein is represented at only
      (1-2)x10(-4)% of dry weight!

PMID- 17521291
TI  - Clinical pharmacology in the geriatric patient.
AB  - Geriatric patients are a subset of older people with multiple comorbidities that
      usually have significant functional implications. Geriatric patients have
      impaired homeostasis and wide inter-individual variability. Comprehensive
      geriatric assessment captures the complexity of the problems that characterize
      frail older patients and can be used to guide management, including prescribing.
      Prescribing for geriatric patients requires an understanding of the efficacy of
      the medication in frail older people, assessment of the risk of adverse drug
      events, discussion of the harm:benefit ratio with the patient, a decision about
      the dose regime and careful monitoring of the patient's response. This requires
      evaluation of evidence from clinical trials, application of the evidence to frail
      older people through an understanding of changes in pharmacokinetics and
      pharmacodynamics, and attention to medication management issues. Given that most
      disease occurs in older people, and that older people are the major recipients of
      drug therapy in the Western world, increased research and a better evidence base
      is essential to guide clinicians who manage geriatric patients.

PMID- 17521292
TI  - Peroxisome proliferator-activated receptors (PPARs) in the control of bone
      metabolism.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear
      transcription factors that regulate the storage and catabolism of dietary fats.
      PPARs constitute molecular targets for the treatment of human metabolic
      disorders, and also play a crucial role in inflammatory-related disease and
      cancer. Recent evidence has revealed the presence of three different PPAR
      isotypes (alpha, beta/delta, and gamma) in different cells of the bone tissue, as
      well as the possible role of PPAR ligands in bone turnover. In the present
      review, the latest knowledge of the expression of PPARs in bone tissue and the
      diverse effects of PPAR ligands on bone metabolism is summarized. PPARs,
      especially of the gamma isotype, could be targets for the treatment of diverse
      bone diseases such as osteoporosis and osteopenia related to either diabetes or
      aging.

PMID- 17521293
TI  - Effect of leptin on peroxidation and antioxidant defense in ethanol-supplemented
      Mus musculus heart.
AB  - The aim of the study was to evaluate the effect of exogenous mouse leptin on
      ethanol-induced cardiac toxicity in mice. Administering ethanol (6.32 g/kg body
      weight p.o.) to 4-week-old healthy mice for 45 days resulted in significantly
      elevated plasma levels of leptin, lactate dehydrogenase (LDH), cardiac lipid
      hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS) and
      significantly decreased cardiac superoxide dismutase, catalase, vitamin C,
      vitamin E, reduced glutathione and glutathione-dependent enzyme levels
      (glutathione peroxidase and glutathione S-transferase). Subsequent to the
      experimental induction of toxicity (i.e., after the initial period of 30 days)
      exogenous leptin was administered (230 microg/kg body weight i.p.) every
      alternate day for 15 days along with the daily dose of ethanol. Leptin
      administration to ethanol-treated mice significantly elevated the levels of
      plasma leptin, LDH and cardiac LOOH, TBARS, whereas the activity of antioxidant
      enzymes and the concentrations of vitamins C and E were further decreased
      significantly. These findings were consistent with our histological observations,
      confirming that leptin enhances cardiac toxicity in ethanol-supplemented mice.

PMID- 17521290
TI  - The protective and destructive roles played by molecular chaperones during ERAD
      (endoplasmic-reticulum-associated degradation).
AB  - Over one-third of all newly synthesized polypeptides in eukaryotes interact with
      or insert into the membrane or the lumenal space of the ER (endoplasmic
      reticulum), an event that is essential for the subsequent folding, post
      translational modification, assembly and targeting of these proteins.
      Consequently, the ER houses a large number of factors that catalyse protein
      maturation, but, in the event that maturation is aborted or inefficient, the
      resulting aberrant proteins may be selected for ERAD (ER-associated degradation).
      Many of the factors that augment protein biogenesis in the ER and that mediate
      ERAD substrate selection are molecular chaperones, some of which are heat- and/or
      stress-inducible and are thus known as Hsps (heat-shock proteins). But,
      regardless of whether they are constitutively expressed or are inducible, it has
      been assumed that all molecular chaperones function identically. As presented in
      this review, this assumption may be false. Instead, a growing body of evidence
      suggests that a chaperone might be involved in either folding or degrading a
      given substrate that transits through the ER. A deeper appreciation of this fact
      is critical because (i) the destruction of some ERAD substrates results in
      specific diseases, and (ii) altered ERAD efficiency might predispose individuals
      to metabolic disorders. Moreover, a growing number of chaperone-modulating drugs
      are being developed to treat maladies that arise from the synthesis of a unique
      mutant protein; therefore it is critical to understand how altering the activity
      of a single chaperone will affect the quality control of other nascent proteins
      that enter the ER.

PMID- 17521294
TI  - Effects of KR-33028, a novel Na+/H+ exchanger-1 inhibitor, on ischemia and
      reperfusion-induced myocardial infarction in rats and dogs.
AB  - The present study was performed to evaluate the cardioprotective effects of KR
      33028, a novel Na+/H+ exchanger subtype 1 (NHE-1) inhibitor, in rat and dog
      models of coronary artery occlusion and reperfusion. In anesthetized rats
      subjected to a 45-min coronary occlusion and a 90-min reperfusion, KR-33028 at 5
      min before occlusion (i.v. bolus) dose-dependently reduced myocardial infarct
      size from 58.0% to 46.6%, 40.3%, 39.7%, 33.1%, and 27.8% for 0.03, 0.1, 0.3, 1.0,
      and 3.0 mg/kg respectively (P < 0.05). In anesthetized beagle dogs that underwent
      a 1.0-h occlusion followed by a 3.0-h reperfusion, KR-33028 (3 mg/kg, i.v. bolus)
      markedly decreased infarct size from 45.6% in vehicle-treated group to 16.4% (P <
      0.05), and reduced the reperfusion-induced release in creatine kinase myocardial
      band isoenzyme (MB), lactate dehydrogenase, troponin-I, glutamic oxaloacetic
      transaminase, and glutamic pyruvic transaminase. In separate experiments to
      assess the effects of timing of treatment, KR-33028 (1 mg/kg, i.v. bolus) given
      10 min before or at reperfusion in rat models also significantly reduced the
      myocardial infarct size (46.3% and 44.1% respectively) compared with vehicle
      treated group. In all studies, KR-33028 caused no significant changes in any
      hemodynamic profiles. In an isolated rat heart model of hypothermic cardioplegia,
      KR-33028 (30 mum), which was added to the heart preservation solution (histidin
      tryptophan-ketoglutarate) during hypothermic cardioplegic arrest, significantly
      improved the recovery of left ventricular developed pressure, heart rate and
      dP/dt(max) after reperfusion. Taken together, these results indicate that KR
      33028 significantly reduced the myocardial infarction induced by ischemia and
      reperfusion in rats and dogs, without affecting hemodynamic profiles.

PMID- 17521295
TI  - Characterization of the human basilar artery contractile response to 5-HT and
      triptans.
AB  - To study the contractile responses of the human basilar artery to 5
      hydroxytryptamine (5-HT), sumatriptan, zolmitriptan and naratriptan, and to
      characterize the 5-HT receptor subtypes involved on those responses, human
      basilar artery rings were prepared for isometric contraction, protein isolation
      and Western blotting analysis. Concentration-response (CR) curves were made for
      all agonists in the absence or in the presence of selective antagonists at 5-HT1B
      (cyanopindolol), 5-HT1D (BRL 15,572) and 5-HT2 (ketanserin) receptors. We also
      used anti-5-HT1B and 5-HT1D receptor antibodies to search for the expression of
      protein of these receptor subtypes. From the CR curves, the relative intrinsic
      activity and potency of these agonists were determined. The ranking order for the
      intrinsic activity was 5-HT > or = sumatriptan > zolmitriptan > or = naratriptan,
      whereas that for the potency was zolmitriptan > or = 5-HT > or = sumatriptan >
      naratriptan. Our results also show that the human basilar artery seems to have a
      mixed population of 5-HT1B/1D receptors mediating the contractile response to
      triptans, which is also suggested by the expression of both receptor subtypes.
      There is also a population of 5-HT2 receptors for which the antimigraine drugs
      used have no apparent affinity. From this study, one can conclude that the second
      generation triptans have lower contractile capacity than sumatriptan, suggesting
      that they have a better cerebrovascular safety profile.

PMID- 17521296
TI  - Melatonin counteracts the loss of agonist-evoked contraction of aortic rings
      induced by incubation.
AB  - Incubation of aortic rings in a culture medium produces phenomena similar to
      those observed with aging, i.e. oxidative stress and inflammation leading to
      increased nitric oxide (NO)-mediated dilation and decreased arterial sensitivity
      to vasoconstrictor agents. We evaluated whether melatonin protects aortic rings
      from such a decrease in vasoreactivity. Two concentrations of melatonin were
      used: 10(-8) M, EC50 for vascular MT1-MT2 receptors, and 10(-5) M, reported as
      anti-oxidant. Anti-oxidant capacity, inducible nitric oxide synthase (iNOS)
      expression and isometric contraction of thoracic aorta rings (Wistar rats) evoked
      by norepinephrine (NE) were assessed. Three days of incubation of aortic rings
      induced iNOS expression and a fall in NE-evoked contraction. When melatonin was
      added to the organ bath, it (10(-5) M) increased (+96%, P < 0.05), but did not
      restore (compared with freshly isolated rings) NE-evoked contraction. Three days
      of treatment with melatonin increased (10(-8) M, +99%) or restored (10(-5) M,
      +216%) NE-evoked contraction (compared with freshly isolated rings). The
      beneficial effects of 10(-8) and 10(-5) M melatonin on NE-evoked contraction were
      abolished in the presence of luzindole (2 x 10(-6) M, a melatonin receptor
      antagonist). The incubation-induced increase in iNOS expression was reduced
      following 3 days of melatonin administration (10(-8) and 10(-5) M). Melatonin
      (10(-5) M) increased catalase activity (6550 +/- 256, P < 0.05 vs. nontreated
      fresh aortic rings 5554 +/- 444 nmol min(-1) mg protein(-1)). In conclusion,
      melatonin counteracts the incubation-induced loss of agonist-evoked contraction
      of aortic rings by a specific receptor-mediated phenomenon involving iNOS
      expression; at higher melatonin concentrations, an anti-oxidant effect is
      probably also involved.

PMID- 17521298
TI  - Effect of peroxisome proliferator-activated receptor-alpha agonist (bezafibrate)
      on gastric secretion and gastric cytoprotection in rats.
AB  - The effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) on
      gastric secretion and gastric cytoprotection was evaluated using five different
      models of gastric ulcers: acetic acid-induced chronic gastric ulcers, pylorus
      ligation, ethanol-induced, indomethacin-induced and ischemia-reperfusion-induced
      gastric ulcers. Bezafibrate, a PPAR-alpha agonist was administered at two
      different doses of 10 and 100 mg/kg body weight intraperitoneanally. Both doses
      of bezafibrate showed significant antiulcer effect in ethanol-induced,
      indomethacin-induced and pylorus ligation-induced gastric ulcers. Bezafibrate
      increased healing of ulcer in acetic acid-induced chronic gastric ulcer model.
      Both doses were also effective in preventing gastric lesions induced by ischemia
      reperfusion. It was concluded that PPAR-alpha activation increases healing of
      gastric ulcers and also prevents development of gastric ulcers in rats.

PMID- 17521297
TI  - Activities of Z-ajoene against tumour and viral spreading in vitro.
AB  - Z-ajoene is a garlic-derived compound with known anti-tumour properties. This
      report argues in favour of pro-apoptotic and cell cycle blockage activities of Z
      ajoene on various cell lines involving activation of the p53-family gene
      products, p53, p63 and p73, at indicated doses. According to its known anti
      proteasome activity, Z-ajoene induced a downregulation of MHC-class I expression
      at the surface of treated cells but did not impair their recognition by CD8+ T
      cells. We further demonstrated a new activity of Z-ajoene against human
      cytomegalovirus spreading in vitro that was mediated by an increased number of
      apoptotic cells after infection. Altogether our data point at the ubiquitous
      efficiency of Z-ajoene as a new compound to fight against cancers of various
      origins including those that put up viruses.

PMID- 17521299
TI  - Cyclooxygenase inhibition attenuates 3-nitropropionic acid-induced neurotoxicity
      in rats: possible antioxidant mechanisms.
AB  - Systemic administration of 3-nitropropionic acid (3-NP), a complex II inhibitor
      of the electron transport chain, causes motor and cognitive deficits that are
      associated with excitotoxicity and excessive free radical generation. Recently,
      cyclooxygenase (COX) inhibitors have been implicated as a neuroprotectant in the
      treatment of various neurological disorders. The present study was designed to
      investigate the effects of COX inhibitors in 3-NP-induced cognitive impairment
      and oxidative stress in rats. Intraperitoneal administration of 3-NP (20 mg/kg
      for 4 days) showed motor abnormalities and cognitive impairment in rats. Chronic
      treatment with naproxen (10 and 20 mg/kg) and valdecoxib (5 and 10 mg/kg) once
      daily for a period of 8 days beginning 4 days prior to 3-NP administration
      significantly improved 3-NP-induced motor and cognitive impairment in rats.
      Biochemical analysis revealed that systemic 3-NP administration significantly
      increased lipid peroxidation and nitrite levels, depleted reduced glutathione
      levels and reduced succinate dehydrogenase (SDH) activity in the brains of rats,
      whereas administration of naproxen, a nonselective COX inhibitor (10 and 20 mg/kg
      p.o.) and valdecoxib, a selective COX-2 inhibitor (5 and 10 mg/kg p.o.)
      significantly attenuated 3-NP-induced oxidative stress. Cyclooxygenase inhibitors
      also significantly restored the decreased SDH activity. The results of the
      present study clearly indicate that naproxen and valdecoxib showed protection
      against 3-NP-induced motor and cognitive impairment by decreasing oxidative
      stress.

PMID- 17521300
TI  - Artemisinin antimalarials moderately affect cytochrome P450 enzyme activity in
      healthy subjects.
AB  - The aim of this study was to investigate which principal human cytochrome P450
      (CYP450) enzymes are affected by artemisinin and to what degree the artemisinin
      derivatives differ with respect to their respective induction and inhibition
      capacity. Seventy-five healthy adults were randomized to receive therapeutic oral
      doses of artemisinin, dihydroartemisinin, arteether, artemether or artesunate for
      5 days (days 1-5). A six-drug cocktail consisting of caffeine, coumarin,
      mephenytoin, metoprolol, chlorzoxazone and midazolam was administered orally on
      days -6, 1, 5 and 10 to assess the activities of CYP1A2, CYP2A6, CYP2C19, CYP2D6,
      CYP2E1 and CYP3A, respectively. Four-hour plasma concentrations of parent drugs
      and corresponding metabolites and 7-hydroxycoumarin urine concentrations were
      quantified by liquid chromatography-tandem mass spectrometry. The 1
      hydroxymidazolam/midazolam 4-h plasma concentration ratio (CYP3A) was increased
      on day 5 by artemisinin [2.66-fold (98.75% CI: 2.10-3.36)], artemether [1.54
      (1.14-2.09)] and dihydroartemisinin [1.25 (1.06-1.47)] compared with day -6. The
      S-4'-hydroxymephenytoin/S-mephenytoin ratio (CYP2C19) was increased on day 5 by
      artemisinin [1.69 (1.47-1.94)] and arteether [1.33 (1.15-1.55)] compared with day
      -6. The paraxanthine/caffeine ratio (CYP1A2) was decreased on day 1 after
      administration of artemisinin [0.27 (0.18-0.39)], arteether [0.70 (0.55-0.89)]
      and dihydroartemisinin [0.73 (0.59-0.90)] compared with day -6. The alpha
      hydroxymetoprolol/metoprolol ratio (CYP2D6) was lower on day 1 compared with day 
      6 in the artemisinin [0.82 (0.70-0.96)] and dihydroartemisinin [0.83 (0.71-0.96)]
      groups, respectively. In the artemisinin-treated subjects this decrease was
      followed by a 1.34-fold (1.14-1.58) increase from day 1 to day 5. These results
      show that intake of artemisinin antimalarials affect the activities of several
      principal human drug metabolizing CYP450 enzymes. Even though not significant in
      all treatment groups, changes in the individual metrics were of the same
      direction for all the artemisinin drugs, suggesting a class effect that needs to
      be considered in the development of new artemisinin derivatives and combination
      treatments of malaria.

PMID- 17521301
TI  - Coxibs: evolution of prescription's behaviour in France.
AB  - The aim of the present study was, first to characterize profiles of coxibs'
      prescribers [general practitioners (GPs) and rheumatologists] in 2002 in France
      and, secondly, to identify factors associated with modification of this profile 1
      year later. All GPs and rheumatologists from Midi-Pyrenees, Aquitaine, Languedoc
      Roussillon and Pays de Loire areas (South of France: 11 050 000 inhabitants) were
      included in the study. For each practitioner, we used data concerning all non
      steroidal anti-inflammatory drugs (NSAIDs) including coxibs reimbursed during
      period 1 (P1; January-March 2002) and period 2 (P2; January-March 2003). The
      ratio between the number of coxibs' prescriptions and the total number of NSAIDs'
      prescriptions (including coxibs) was used to define the two profiles of
      prescribers, one with a low level of coxibs' prescriptions and another one with a
      high level of coxibs' prescriptions. Characteristics of practitioners and
      characteristics of their practices were compared according to this profile. In
      the second step, we investigated the characteristics (of practitioners and
      practices) associated with an increase in the level of coxibs' prescriptions in
      P2 for practitioners with a low level of coxibs' prescriptions in P1. Results are
      expressed as odds ratio with their 95% confidence intervals. A positive
      statistical link was found between a high level of coxibs' prescriptions, the
      speciality of rheumatologist or extra costs for consultation. In contrast, a
      negative association was observed with female gender or age below 44 years. No
      relationship was found with the status of referent. Concerning practices'
      characteristics of practitioners, there was a positive statistical link between a
      high ratio of coxibs' prescriptions and high co-prescriptions of gastroprotective
      agents and a negative association with a high number of acts, a high proportion
      of patients with chronic disabling diseases (CDD) or a high number of patients
      between 15 and 64 years. There was no statistical link with proportion of
      patients covered by Universal Medical Coverage (UMC) or aged more than 65 years.
      Among the factors involved in the increase in the ratio (between P1 and P2), no
      relationship was found with practitioners' characteristics. In contrast, some
      factors related to practices (level of gastroprotective co-prescriptions, number
      of acts, number of CDD patients) were related to a change in coxibs'
      prescriptions between P1 and P2. This study allowed to discuss some relationships
      between coxibs' prescription and practitioners' (age, gender, medical speciality
      or extra costs for consultation) or practices' (level of medical practice,
      patients' age, number of CDD patients or level of gastroprotective prescriptions)
      characteristics. In contrast, some other factors like the referent status or the
      number of patients with UMC are not related. Physicians, initially low
      prescribers of coxibs and increasing their coxibs' prescriptions during the
      period of our study, were those with a high level of gastroprotective
      prescriptions, a low number of acts or a small proportion of CDD patients.

PMID- 17521302
TI  - Antiplatelet drug use preceding the onset of intracerebral hemorrhage is
      associated with increased mortality.
AB  - Recent studies highlight the contribution of antiplatelet therapy to clinical
      severity and increased mortality of intracerebral hemorrhage (ICH) but results
      are discrepant. The aim of this report was to evaluate the association between
      antiplatelet drug use preceding the onset of ICH and the mortality, assessed at
      regular intervals, among patients with acute ICH. We analyzed data from a
      randomized study which enrolled consecutive patients with a documented acute ICH
      to evaluate the efficacy of intermittent pneumatic compression of the legs in
      venous thrombosis prevention. Clinical characteristics and treatment used before
      the onset of ICH were checked at the time of inclusion. Mortality was assessed at
      regular intervals until 3 months after ICH diagnosis. Among 138 patients included
      in this report, 30 were current users of antiplatelet therapy at the time of ICH;
      they were significantly older and less frequently heavy drinkers than non-users
      of antiplatelet drugs. Mortality rates were 20% at 8 days, 40% at 1 month, and
      47% at 3 months among antiplatelet drug users compared with 6.5%, 13% and 19%
      among non-users. The corresponding estimated risks for mortality related to
      antiplatelet drug use were 3.6 (95% CI 1.1-12), 4.5 (95% CI 1.8-11), and 3.6 (95%
      CI 1.5-8.6). Adjusted for age, hypertension and alcohol over use, antiplatelet
      therapy remained significantly associated with an increased mortality rate of
      acute ICH. Current antiplatelet drug use preceding the onset of ICH is associated
      with increased short-term ICH mortality, independently of age.

PMID- 17521304
TI  - Reduction of dispersion of repolarization and prolongation of postrepolarization
      refractoriness explain the antiarrhythmic effects of quinidine in a model of
      short QT syndrome.
AB  - BACKGROUND: Short QT syndrome (SQTS) is a newly described ion channelopathy,
      characterized by a short QT interval resulting from an accelerated cardiac
      repolarization, associated with syncope, atrial fibrillation, and sudden cardiac
      death due to ventricular fibrillation. As therapeutic options in SQTS are still
      controversial, we examined antiarrhythmic mechanisms in an experimental model of
      SQTS. METHODS AND RESULTS: Pinacidil, an I(K-ATP) channel opener, was
      administered in increasing concentrations (50-100 microM) in 48 Langendorff
      perfused rabbit hearts and led to a significant reduction of action potential
      duration and QT interval, thereby mimicking SQTS. Eight simultaneously recorded
      monophasic action potentials demonstrated an increase in dispersion of
      repolarization, especially between the left and the right ventricle. During
      programmed ventricular stimulation with up to two extrastimuli, pinacidil
      significantly increased the inducibility of ventricular fibrillation (1 heart
      under baseline conditions, 29 hearts during pinacidil administration; P =
      0.0001). Additional treatment with the I(Kr) blocker sotalol (100 microM) and the
      class I antiarrhythmic drugs flecainide (2 microM) and quinidine (0.5 microM)
      randomly assigned to three groups of 16 hearts led to prolongation of
      repolarization as well as refractory period. Sotalol or flecainide did not reduce
      the rate of inducibility of ventricular fibrillation significantly (P = 0.63; P =
      0.219). However, quinidine reduced the inducibility of ventricular fibrillation
      by 73% (P = 0.008). The antiarrhythmic potential of quinidine was associated with
      a significantly greater prolongation of MAP duration, refractoriness, and
      postrepolarization refractoriness (PRR) as compared with sotalol and flecainide.
      Moreover, quinidine, in contrast to sotalol and flecainide, reduced dispersion of
      repolarization. CONCLUSION: Pinacidil mimics SQTS via increasing potassium
      outward currents, thereby facilitating inducibility of ventricular fibrillation.
      Quinidine demonstrates superior antiarrhythmic properties in the treatment of
      ventricular fibrillation in this model as compared with sotalol and flecainide
      because of its effects on refractoriness, PRR, and by reducing dispersion of
      repolarization.

PMID- 17521305
TI  - Quinidine in short QT syndrome: an old drug for a new disease.

PMID- 17521306
TI  - Tako-tsubo cardiomyopathy complicating left atrial radiofrequency ablation.
AB  - Two female patients undergoing left atrial radiofrequency catheter ablation
      developed Tako-tsubo cardiomyopathy. This reversible form of left ventricular
      dysfunction is known to occur under conditions associated with marked sympathetic
      nervous activation. Radiofrequency catheter ablation in the left atrium can
      damage autonomic ganglionated plexi, leading to vagal withdrawal, thus resulting
      in enhanced sympathetic tone. Tako-tsubo cardiomyopathy has not been previously
      described following radiofrequency catheter ablation.

PMID- 17521308
TI  - Sample size needed to detect gene-gene interactions using linkage analysis.
AB  - Gene-gene interactions have received much attention recently because most human
      traits may be under the control of several genetic factors, as well as
      environmental factors, and these factors likely interact among each other to
      influence these traits. Gauderman (2002) and Wang & Zhao (2003) have reported
      systematic studies on the statistical power to detect gene-gene interactions
      through association studies. In this article we investigated the power of the
      affected sib pair (ASP) design to detect gene-gene interaction at two disease
      loci. Different definitions of gene-gene interaction were considered and
      different disease models (including both logistic models considered in previous
      studies and several two-locus models with fixed penetrances) were examined. Our
      results indicate that comparisons between power to detect gene-gene interaction
      using ASP designs and association designs heavily depend on the definition of
      gene-gene interaction. Under the definition of gene-gene interaction with
      departure from independence between two marginal IBD sharings, the association
      design is much more powerful than the ASP design, and the additive model is more
      powerful than dominant and recessive models for rare diseases, while for common
      diseases for example with a population prevalence of 10%, the recessive model is
      more powerful than the additive and dominant models. Under the definitions of
      departure from a multiplicative model, additive model, and heterogeneity model
      (Risch, 1990), the ASP design is as powerful as, or more powerful than, both
      family-based and population-based association designs for rare disease,, but less
      powerful for more common diseases. Under the definition of correlation between
      two marginal IBD sharings, the association design is much more powerful than the
      ASP design.

PMID- 17521309
TI  - Interaction of genetic risk factors confers higher risk for thrombotic stroke in
      male Chinese: a multicenter case-control study.
AB  - Stroke is a polygenic or multifactorial disease, and each single susceptibility
      gene has modest effects. We hypothesize that combined effects of multiple genes
      might confer a higher stroke risk than a single susceptibility gene. To test our
      hypothesis we initially recruited 2000 stroke patients (44.3% thrombosis, 28.3%
      lacunar infarction and 27.4% intracerebral hemorrhage) and 2000 controls, and
      examined 6 polymorphisms in 5 candidate genes for stroke. Plasma lipoprotein(a)
      [Lp(a)] level was defined as a categorical variable and also included.
      Interactions between genetic risk factors were detected by the multifactor
      dimensionality reduction (MDR) method and further evaluated by multivariate
      logistic regression analyses. A significant combined effect on stroke due to the
      C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR), the T2354A
      polymorphism of 5-lipoxygenase activating protein (ALOX5AP), and Lp(a) level, was
      detected using the MDR method. Furthermore, the combination of MTHFR 677TT,
      ALOX5AP 2354AA and Lp(a) elevation (Lp(a) concentration > or = 30 mg/dL) was
      found to be strongly associated with thrombotic stroke in males (OR, 10.419;
      95%CI, 2.602 to 41.749; P= 0.001) using the multivariate logistic regression
      model. In conclusion, our results show that a combination of genetic risk factors
      can confer a higher risk for stroke than a single risk factor, indicating that
      people with multiple genetic risk factors have a higher risk of stroke and should
      be targets for prevention of this disease.

PMID- 17521310
TI  - Deconstructing Jaco: genetic heritage of an Afrikaner.
AB  - It is often assumed that Afrikaners stem from a small number of Dutch immigrants.
      As a result they should be genetically homogeneous, show founder effects and be
      rather inbred. By disentangling my own South African pedigree, that is on average
      12 generations deep, I try to quantify the genetic heritage of an Afrikaner. As
      much as 6% of my genes have been contributed by slaves from Africa, Madagascar
      and India, and a woman from China. This figure compares well to other genetic and
      genealogical estimates. Seventy three percent of my lineages coalesce into common
      founders, and I am related in excess of 10 times to 20 founder ancestors (30
      times to Willem Schalk van der Merwe). Significant founder effects are thus
      possible. The overrepresentation of certain founder ancestors is in part
      explained by the fact that they had more children. This is remarkable given that
      they lived more than 300 years (or 12 generations) ago. DECONSTRUCT, a new
      program for pedigree analysis, identified 125 common ancestors in my pedigree.
      However, these common ancestors are so distant from myself, paths of between 16
      and 25 steps in length, that my inbreeding coefficient is not unusually high (f
      approximately 0.0019).

PMID- 17521311
TI  - Desloratadine improves quality of life and symptom severity in patients with
      allergic rhinitis.
AB  - BACKGROUND: Desloratadine is associated with decreased signs and symptoms and
      improved nasal airflow in multiple clinical trials in patients with allergic
      rhinitis (AR). The effect of desloratadine on quality of life (QOL) in AR has not
      been widely reported to date. We compared the effects of desloratadine and
      placebo on QOL in seasonal AR using validated, disease-specific measures.
      METHODS: This was a multicenter, double-blind, randomized, parallel-group study
      of desloratadine 5 mg or placebo daily for 2 weeks in patients with symptomatic
      seasonal AR. QOL was assessed at baseline and at day 14 using the
      Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). AR signs/symptoms and
      the global response to therapy were measured at baseline and at day 14;
      signs/symptoms were also rated AM/PM in patient diaries. Adverse events (AE) were
      recorded. RESULTS: Overall 234 patients received desloratadine and 249 received
      placebo. At day 14 desloratadine was associated with a significantly larger
      improvement from baseline in the mean total RQLQ score vs placebo (P = 0.0003).
      Desloratadine also led to significant improvements from baseline in all RQLQ sub
      domains (P < or = 0.043). At day 14 significant decreases from baseline were
      noted in the desloratadine group for total nasal (P = 0.0003), total non-nasal (P
      = 0.001) and total symptoms scores (P = 0.0001). Morning AR symptoms were
      significantly decreased in the desloratadine group after 1 day of treatment.
      Desloratadine was well tolerated, with an AE rate similar to placebo. CONCLUSION:
      Significant reductions in signs and symptoms of AR with desloratadine treatment
      were accompanied by improved disease-specific QOL measures.

PMID- 17521312
TI  - EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin
      hypersensitivity.
AB  - Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the
      most common causes of adverse drug reactions. Majority of them are of the
      hypersensitivity type. The two frequent clinical presentations of aspirin
      hypersensitivity are: aspirin-induced bronchial asthma/rhinosinusitis (AIA/R) and
      aspirin-induced urticaria/angioedema (AIU). The decisive diagnosis is based on
      provocation tests with aspirin, as the in vitro test does not hold diagnostic
      value as yet. Detailed protocols of oral, bronchial and nasal aspirin provocation
      tests are presented. Indications, contraindications for the tests, the rules of
      drug withdrawal and equipment are reviewed. Patient supervision and
      interpretations of the tests are proposed.

PMID- 17521313
TI  - Allergenic pollen and pollen allergy in Europe.
AB  - The allergenic content of the atmosphere varies according to climate, geography
      and vegetation. Data on the presence and prevalence of allergenic airborne
      pollens, obtained from both aerobiological studies and allergological
      investigations, make it possible to design pollen calendars with the approximate
      flowering period of the plants in the sampling area. In this way, even though
      pollen production and dispersal from year to year depend on the patterns of
      preseason weather and on the conditions prevailing at the time of anthesis, it is
      usually possible to forecast the chances of encountering high atmospheric
      allergenic pollen concentrations in different areas. Aerobiological and
      allergological studies show that the pollen map of Europe is changing also as a
      result of cultural factors (for example, importation of plants such as birch and
      cypress for urban parklands), greater international travel (e.g. colonization by
      ragweed in France, northern Italy, Austria, Hungary etc.) and climate change. In
      this regard, the higher frequency of weather extremes, like thunderstorms, and
      increasing episodes of long range transport of allergenic pollen represent new
      challenges for researchers. Furthermore, in the last few years, experimental data
      on pollen and subpollen-particles structure, the pathogenetic role of pollen and
      the interaction between pollen and air pollutants, gave new insights into the
      mechanisms of respiratory allergic diseases.

PMID- 17521314
TI  - Development and validation of an electronic version of the Rhinoconjunctivitis
      Quality of Life Questionnaire.
AB  - BACKGROUND: As clinicians and pharmaceutical companies move from paper versions
      of health status questionnaires to electronic versions, it cannot be assumed that
      adaptations to other media will produce valid data. AIMS: The aims of this study
      were to (1) adapt the Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ(S);
      standardized version], for the Palm Treo 650, (2) test the device for ease and
      accuracy of understanding and (3) examine the validity of the electronic version
      by comparing it with the original paper version of the RQLQ(S). METHODS: Seventy
      adults with current rhinoconjunctivitis symptoms completed the electronic and
      paper versions of the RQLQ(S). They were randomized to complete either the paper
      or the electronic version first. After a 2-h break, they completed the other
      version. RESULTS: Concordance between paper and electronic versions for the
      overall RQLQ(S) score was acceptable with an intraclass correlation coefficient
      of 0.95 and there was no evidence of bias (P = 0.13). Concordance for the seven
      individual domains ranged from 0.86 to 0.94. A small but significant bias was
      observed in the activity and sleep domains (P = 0.02). Completion times were
      quicker with paper (4.1 vs 4.9 min, P < 0.0001). About 51% of patients preferred
      electronic, 17% preferred paper and 31% had no preference. CONCLUSIONS: This
      electronic version of the RQLQ(S) was easy for patients to use and the
      concordance between paper and this version on the Palm Treo 650 provides evidence
      of the validity of this electronic version.

PMID- 17521315
TI  - Quantitative and qualitative adaptation of human skeletal muscle mitochondria to
      hypoxic compared with normoxic training at the same relative work rate.
AB  - AIM: To investigate if training during hypoxia (H) improves the adaptation of
      muscle oxidative function compared with normoxic (N) training performed at the
      same relative intensity. METHOD: Eight untrained volunteers performed one-legged
      cycle training during 4 weeks in a low-pressure chamber. One leg was trained
      under N conditions and the other leg under hypobaric hypoxia (526 mmHg) at the
      same relative intensity as during N (65% of maximal power output, W(max)). Muscle
      biopsies were taken from vastus lateralis before and after the training period.
      Muscle samples were analysed for the activities of oxidative enzymes [citrate
      synthase (CS) and cytochrome c oxidase (COX)] and mitochondrial respiratory
      function. RESULTS: W(max) increased with more than 30% over the training period
      during both N and H. CS activity increased significantly after training during N
      conditions (+20.8%, P < 0.05) but remained unchanged after H training (+4.5%, ns)
      with a significant difference between conditions (P < 0.05 H vs. N). COX activity
      was not significantly changed by training and was not different between exercise
      conditions [+14.6 (N) vs. -2.3% (H), ns]. Maximal ADP stimulated respiration
      (state 3) expressed per weight of muscle tended to increase after N (+31.2%, P <
      0.08) but not after H training (+3.2%, ns). No changes were found in state four
      respiration, respiratory control index, P/O ratio, mitochondrial Ca(2+)
      resistance and apparent Km for oxygen. CONCLUSION: The training-induced increase
      in muscle oxidative function observed during N was abolished during H. Altitude
      training may thus be disadvantageous for adaptation of muscle oxidative function.

PMID- 17521316
TI  - Minor histocompatibility antigens as targets for immunotherapy using allogeneic
      immune reactions.
AB  - Minor histocompatibility antigens (mHag) were originally identified as antigens
      causing graft rejection or graft-versus-host disease in human leukocyte antigen
      (HLA)-matched allogeneic transplantation. Molecular identification has revealed
      most to be major histocompatibility complex (MHC)-bound short peptide fragments
      encoded by genes which are polymorphic due to single nucleotide polymorphisms
      (SNP). Genotypic disparity of SNP between transplantation donors and recipients
      gives rise to mHag as non-self antigens for both the donor and the recipient.
      Subsequently, mHag have been explored as immunotherapeutic antigens for use
      against recurring hematological malignancies after allogeneic hematopoietic cell
      transplantation (HCT), because mHag expressed only on hematopoietic cells are
      considered to augment graft-versus-leukemia/lymphoma (GVL) effects without
      increasing the risk of life-threatening graft-versus-host disease (GVHD).
      Accumulating evidence suggests that T-cell responses to mHag aberrantly expressed
      on solid tumor cells are also involved in the eradication of sensitive tumors
      such as renal cell carcinomas following HCT. Over the past decade, the number of
      putative GVL-directed mHag has increased to a level that covers more than 30% of
      the Japanese patient population, so that clinical trials may now be executed in
      the setting of either vaccination or adoptive immunotherapy. As it is expected
      that immune responses to alloantigens are more powerful than to tumor antigens
      mostly derived from overexpressed self-proteins, mHag-based immunotherapy may
      lead to a new treatment modality for high-risk malignancies following allogeneic
      HCT.

PMID- 17521318
TI  - Interferon-gamma does not break, but promotes the immunosuppressive capacity of
      adult human mesenchymal stem cells.
AB  - The ability of mesenchymal stem cells (MSC) to suppress alloresponsiveness is
      poorly understood. Herein, an allogeneic mixed lymphocyte response was used as a
      model to investigate the mechanisms of MSC-mediated immunomodulation. Human MSC
      are demonstrated to express the immunosuppressive cytokines hepatocyte growth
      factor (HGF), interleukin (IL)-10 and transforming growth factor (TGF)-beta1 at
      concentrations that suppress alloresponses in vitro. MSC also express
      cyclooxygenase 1 and 2 and produce prostaglandin E2 constitutively. Blocking
      studies with indomethacin confirmed that prostaglandins contribute to MSC
      mediated allosuppression. The proinflammatory cytokine interferon (IFN)-gamma did
      not ablate MSC inhibition of alloantigen-driven proliferation but up-regulated
      HGF and TGF-beta1. IFN-gamma also induced expression of indoleamine 2,3,
      dioxygenase (IDO), involved in tryptophan catabolism. Use of an antagonist, 1
      methyl-L-tryptophan, restored alloresponsiveness and confirmed an IDO
      contribution to IFN-gamma-induced immunomodulation by MSC. Addition of the
      tryptophan catabolite kynurenine to mixed lymphocyte reactions (MLR), blocked
      alloproliferation. These findings support a model where IDO exerts its effect
      through the local accumulation of tryptophan metabolites rather than through
      tryptophan depletion. Taken together, these data demonstrate that soluble
      factors, or products derived from MSC, modulate immune responses and suggest that
      MSC create an immunosuppressive microenvironment capable of modulating
      alloresponsiveness even in the presence of IFN-gamma.

PMID- 17521317
TI  - Natural killer cells, killer immunoglobulin-like receptors and human leucocyte
      antigen class I in disease.
AB  - Natural killer cells constitute a potent, rapid part of the innate immune
      response to infection or transformation, and also generate a link to priming of
      adaptive immunity. Their function can encompass direct cytotoxicity as well as
      the release of cytokines and chemokines. In humans, a major component of natural
      killer (NK) cell target recognition depends mainly on the surveillance of human
      leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors
      (KIR). Different KIR can transmit inhibitory or activatory signals to the cell,
      and effector function is considered to result from the balance of these
      contributing signals. The regulation of NK cell responses depends on a number of
      variables: KIR genotype, HLA genotype, heterozygosity versus homozygosity for
      these, whether there is cognate recognition between the HLA and KIR products
      carried by an individual, clonal variation between individual NK cells in KIR
      expression, and the specific modulation of HLA expression by infection,
      transformation or peptide binding. Different HLA/KIR genotypes can impart
      different thresholds of activation to the NK cell repertoire and such genotypic
      variation has been found to confer altered risk in a number of diseases including
      human immunodeficiency virus (HIV) susceptibility and progression, hepatitis C
      virus clearance, idiopathic bronchiectasis, autoimmunity and cancer.

PMID- 17521319
TI  - Selection of probiotic bacteria for prevention of allergic diseases:
      immunomodulation of neonatal dendritic cells.
AB  - Modification of intestinal microbiota early in life by administration of
      probiotic bacteria may be a potential approach to prevent allergic disease. To
      select probiotic bacteria for in vivo purposes, we investigated the capacity of
      probiotic bacteria to interact with neonatal dendritic cells (DC) and studied the
      ensuing T cell polarizing effect. Immature DC were generated from cord blood
      derived monocytes and maturation was induced by maturation factors (MF),
      lipopolysaccharide (LPS) plus MF and Bifidobacterium bifidum, B. infantis,
      Lactobacillus salivarius, Lactococcus lactis alone or combined with MF. After 12
      days of co-culture with DC and Staphylococcus aureus enterotoxin B (SEB) as
      antigenic stimulus, cytokine production by autologous T cells was determined by
      intracellular cytokine staining. Additionally, cells were stimulated with CD3 and
      CD28 monoclonal antibodies and cytokines were measured in supernatants by
      multiplex assay. The probiotic strains induced partial maturation of DC. Full
      maturation of DC was induced for all strains tested when MF was added. The
      percentage of interleukin (IL)-4 producing T cells was lower in T cell cultures
      stimulated with B. bifidum matured DC compared to MF and LPS matured DC, which
      coincided with a higher percentage of interferon (IFN)-gamma-producing T cells.
      Furthermore, T cells stimulated by B. bifidum matured DC produced significantly
      more IL-10 compared to MF matured DC. Selected species of the Bifidobacterium
      genus prime in vitro cultured neonatal DC to polarize T cell responses and may
      therefore be candidates to use in primary prevention of allergic diseases.

PMID- 17521320
TI  - Anti-oxidized low-density lipoprotein antibodies in myeloperoxidase-positive
      vasculitis patients preferentially recognize hypochlorite-modified low density
      lipoproteins.
AB  - Many patients surviving vasculitis are prone to accelerated atherosclerosis and
      often have enhanced levels of antibodies to oxidized low-density lipoprotein
      (oxLDL). To measure anti-oxLDL antibodies, oxidation of LDL is achieved with
      copper (Cu) or malondialdehyde (MDA). Because, in vivo, LDL may be oxidized with
      myeloperoxidase (MPO) or its product hypochlorite, we measured anti-hypochlorite
      LDL antibodies in patients with vasculitis, haemodialysis patients and healthy
      controls. A newly developed enzyme-linked immunosorbent assay (ELISA) was used to
      detect antibodies to oxLDL as modified by hypochlorite. Results are compared with
      data obtained by standard LDL oxidation using MDA-LDL or Cu-LDL as substrate.
      Results were compared between anti-neutrophil cytoplasmic antibodies (ANCA)
      associated vasculitis (AAV) patients (n = 93), haemodialysis (HD) patients (n =
      59) and healthy controls (HC; n = 43). Furthermore, patients with MPO-ANCA
      associated vasculitis (n = 47) were compared with patients with proteinase 3
      (PR3)-ANCA associated vasculitis (n = 46). Optimal cut-off points were determined
      by receiver operator characteristic (ROC) curve analysis. Anti-oxLDL antibodies
      are enhanced in AAV patients (MDA-LDL and hypochlorite-LDL) and in HD patients
      (hypochlorite-LDL), when compared to HC. Furthermore, patients with MPO-ANCA
      associated vasculitis had higher levels of antibodies to hypochlorite-LDL than
      patients with PR3-ANCA-associated vasculitis. Our newly developed assay, in which
      hypochlorite-LDL is used as substrate, seems a more sensitive assay than
      traditional assays to measure oxLDL antibodies. Furthermore, our results suggest
      that enhanced MPO-mediated LDL oxidation occurs in patients with MPO-ANCA.

PMID- 17521321
TI  - The role of CD11c(+) hepatic dendritic cells in the induction of innate immune
      responses.
AB  - The role of the liver in the initiation and maintenance of tolerance is a
      critical immune function that involves multiple lineages of immune cells.
      Included within these populations are liver dendritic cells (DCs). Although there
      has been significant work on the phenotypic and functional roles of splenic and
      bone marrow dendritic cells, as well as their subsets, comparable studies in
      liver have often been difficult. To address this issue we have isolated, from
      C57BL/6 mice, relatively pure populations of DCs and compared phenotype and
      function to the data from spleen using flow cytometry, cell sorter assisted
      purification and culture, morphology by cytospin and May-Giemsa staining, cell
      cycle progression, antigen uptake, cytokine production and allo-activation
      potential. natural killer (NK)1.1(-)CD11c(+) liver DC subsets (conventional DCs,
      T cell receptor (TcR)beta(-)NK1.1(-)CD11c(+)B220(-) and plasmacytoid DCs,
      TcRbeta(-)NK1.1(-)CD11c(+)B220(+)) efficiently endocytose dextran and produce
      significant levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and
      IL-12 p40 in response to Toll-like receptor (TLR) ligands, with responses higher
      than splenic DCs. There is also a differential capability of hepatic DCs to
      respond to innate signals. Indeed, CD11c(+) hepatic DCs have a greater capacity
      to respond to innate stimulation but are less capable of inducing CpG activated
      allogeneic T cells. These data suggest that hepatic dendritic cells function as a
      critical bridge between innate and adaptive immunity and are capable of inducing
      stronger innate responses with a lower capacity for allo-stimulation than splenic
      dendritic cells. These properties of liver dendritic cells contribute to their
      unique role in the induction of tolerance.

PMID- 17521322
TI  - Meta-analysis of myeloperoxidase G-463/A polymorphism in anti-neutrophil
      cytoplasmic autoantibody-positive vasculitis.
AB  - Wegener's granulomatosis, microscopic polyangiitis and Churg Strauss syndrome are
      small-vessel vasculitides associated with anti-neutrophil cytoplasmic antibodies
      (ANCA) directed against proteinase 3 (PR3) and myeloperoxidase (MPO). A G to A
      polymorphism at position 463 in the promoter region of the MPO gene, which leads
      to the loss of a SP1 transcription binding site in an Alu hormone responsive
      element, reduces MPO expression. We hypothesized that MPO alleles may play a role
      in determining disease susceptibility or severity in ANCA-associated vasculitis
      (AASV). MPO genotypes were determined by restriction fragment length polymorphism
      polymerase chain reaction (RFLP/PCR) in 134 Caucasian patients (Wegener's
      granulomatosis, n = 69; microscopic polyangiitis, n = 65; PR3-ANCA n = 91; MPO
      ANCA, n = 43) and 150 matched healthy controls. There was no difference in
      survival to renal failure or death in patients with the different MPO alleles
      (chi(2) = 0.904, P = 0.6362) or in presenting serum creatinine concentration
      based on MPO genotype (chi(2) = 0.389, P = 0.8232). There was no significant
      difference in genotype frequencies between controls (13AA, 102GG, 35GA) and
      patients (14AA, 97GG, 23GA: chi(2) = 1.75, P = 0.417), patients with Wegener's
      granulomatosis (5AA, 53GG, 11GA: chi(2) = 1.864, P = 0.3938) or patients with
      microscopic polyangiitis (9AA, 44GG, 12GA: chi(2) = 1.682, P = 0.4317). A meta
      analysis of our study and two previous studies showed that there was no
      association between the myeloperoxidase G-463/A polymorphism and the risk of
      developing ANCA-associated vasculitis; GG versus GA plus AA (odds ratio 1.14; 95%
      confidence interval 0.86-1.50). The MPO G-463/A polymorphism is not a risk factor
      for the development or severity of AASV.

PMID- 17521323
TI  - Hypothermic preservation of lung allograft inhibits cytokine-induced
      chemoattractant-1, endothelial leucocyte adhesion molecule, vascular cell
      adhesion molecule-1 and intracellular adhesion molecule-1 expression.
AB  - Organ dysfunction is a major clinical problem after lung transplantation.
      Prolonged cold ischaemia and reperfusion injury are believed to play a central
      role in this complication. The influence of cold preservation on subsequent warm
      reperfusion was studied in an isolated, ventilated and perfused rat lung. Rat
      lungs were flushed with cold Perfadex-solution and stored at 4 degrees C for
      different time periods. Thereafter lungs were perfused and ventilated for up to 3
      h. Physiological parameters, production of inflammatory mediators and leucocyte
      infiltration were measured before and after perfusion. Lungs subjected to a cold
      ischaemia time of up to 6 h showed stable physiological conditions when perfused
      for 3 h. However, cold-ischaemia time beyond 6 h resulted in profound tissue
      oedema, thereby impairing ventilation and perfusion. Warm reperfusion and
      ventilation per se induced a strong inflammatory response, as demonstrated by a
      significant up-regulation of chemokines and adhesion molecules (cytokine-induced
      chemoattractant-1, intracellular adhesion molecule and endothelial leucocyte
      adhesion molecule), accompanied by enhanced leucocyte infiltration. Although the
      up-regulation of inflammatory mediators was blunted in lungs that were subjected
      to cold ischaemia, this did not influence leucocyte infiltration. In fact, cold
      ischaemia time correlated with leucocyte sequestration. Although cold
      preservation inhibits the expression of inflammatory mediators it does not affect
      leucocyte sequestration during warm reperfusion. Cold preservation might cause
      impairment of the endothelial barrier function, as evidenced by tissue oedema and
      profound leucocyte infiltration.

PMID- 17521325
TI  - Susceptibility genes in Graves' ophthalmopathy: searching for a needle in a
      haystack?
AB  - The variety of clinical presentations of eye changes in patients with Graves'
      disease suggests that complex interactions between genetic, environmental,
      endogenous and local factors influence the development/severity of Graves'
      ophthalmopathy (GO). At present, the role of genetic factors in the development
      of GO remains unknown. Based on small case-control association studies with
      candidate genes, several susceptibility loci in GO have been proposed. These are
      human leucocyte antigen (HLA, 6p21.3), cytotoxic T-lymphocyte antigen-4 (CTLA-4,
      2q33), tumour necrosis factor (TNF, 6p21.3), interferon-gamma (IFN-gamma, 12q14),
      intercellular adhesion molecule-1 (ICAM-1, 19p13), and thyroid stimulating
      hormone receptor gene (TSH-R, 14q31). Unfortunately, these results were either
      not confirmed or require replication in larger studies. There are many reasons
      for the lack of reproducibility of association studies in GO, including poor
      characterization of the studied groups and small sample sizes, which may result
      in both false positive and negative results. Thus, the genetic background of GO
      remains to be elucidated in future research. However, the possibility that GO may
      be a genetically heterogeneous disorder, or that the development of GO may be
      predominantly influenced by environmental factors such as cigarette smoking, can
      not be disregarded.

PMID- 17521324
TI  - Identification of prediabetes in first-degree relatives at intermediate risk of
      type I diabetes.
AB  - Prevention trials of type I diabetes are limited by recruitment of individuals at
      high risk of the disease. We investigated whether demographic and biological
      characteristics can identify rapid progressors among first-degree relatives of
      known patients at intermediate (< 10%) 5-year risk. Diabetes-associated
      antibodies, random proinsulin : C-peptide (PI/C) ratio and HLA DQ genotype were
      determined (repeatedly) in 258 islet antibody-positive IA-2Antibody-negative
      (Abpos/IA-2Aneg) normoglycaemic first-degree relatives. During follow-up (median
      81 months), 14 of 258 Abpos/IA-2Aneg relatives developed type I diabetes; 13
      (93%) of them had persistent antibodies conferring a 12% [95% confidence interval
      (CI): 5-19%] 5-year risk of diabetes. In Abpos/IA-2Aneg relatives with persistent
      antibodies (n = 126), the presence of >/= 1 HLA DQ susceptibility haplotype in
      the absence of a protective haplotype (P = 0.033) and appearance on follow-up of
      a high PI/C ratio (P = 0.007) or IA-2A-positivity (P = 0.009) were identified as
      independent predictors of diabetes. In persistently antibody-positive relatives
      with HLA DQ risk a recurrently high PI/C ratio or development of IA-2A identified
      a subgroup (n = 32) comprising 10 of 13 (77%) prediabetic relatives and conferred
      a 35% (95% CI: 18-53%) 5-year risk. Under age 15 years, 5-year progression (95%
      CI) was 57% (30-84%) and sensitivity 62%. In the absence of IA-2A, the
      combination of antibody persistence, HLA DQ risk and elevated PI/C ratio or later
      development of IA-2A and young age defines a subgroup of relatives with a high
      risk of type I diabetes (>/= 35% in 5 years). Together with initially IA-2A
      positive relatives these individuals qualify for standardized beta cell function
      tests in view of prevention trials.

PMID- 17521326
TI  - Role of the small Rho GTPases Rac1 and Cdc42 in host cell invasion of
      Campylobacter jejuni.
AB  - Host cell invasion of the food-borne pathogen Campylobacter jejuni is one of the
      primary reasons of tissue damage in humans but molecular mechanisms are widely
      unclear. Here, we show that C. jejuni triggers membrane ruffling in the
      eukaryotic cell followed by invasion in a very specific manner first with its tip
      followed by the flagellar end. To pinpoint important signalling events involved
      in the C. jejuni invasion process, we examined the role of small Rho family
      GTPases. Using specific GTPase-modifying toxins, inhibitors and GTPase expression
      constructs we show that Rac1 and Cdc42, but not RhoA, are involved in C. jejuni
      invasion. In agreement with these observations, we found that internalization of
      C. jejuni is accompanied by a time-dependent activation of both Rac1 and Cdc42.
      Finally, we show that the activation of these GTPases involves different host
      cell kinases and the bacterial fibronectin-binding protein CadF. Thus, CadF is a
      bifunctional protein which triggers bacterial binding to host cells as well as
      signalling leading to GTPase activation. Collectively, our results suggest that
      C. jejuni invade host target cells by a unique mechanism and the activation of
      the Rho GTPase members Rac1 and Cdc42 plays a crucial role in this entry process.

PMID- 17521327
TI  - A major role for intestinal epithelial nucleotide oligomerization domain 1 (NOD1)
      in eliciting host bactericidal immune responses to Campylobacter jejuni.
AB  - Campylobacter jejuni is the foremost cause of bacterial-induced diarrhoeal
      disease worldwide. Although it is well established that C. jejuni infection of
      intestinal epithelia triggers host innate immune responses, the mechanism(s)
      involved remain poorly defined. Innate immunity can be initiated by families of
      structurally related pattern-recognition receptors (PRRs) that recognize specific
      microbial signature motifs. Here, we demonstrated maximal induction of epithelial
      innate responses during infection with live C. jejuni cells. In contrast when
      intestinal epithelial cells (IECs) were exposed to paraformaldehyde-fixed
      bacteria, host responses were minimal and a marked reduction in the number of
      intracellular bacteria was noted in parallel. These findings suggested a role for
      intracellular host-C. jejuni interactions in eliciting early innate immunity. We
      therefore investigated the potential involvement of a family of intracellular,
      cytoplasmic PRRs, the nucleotide-binding oligomerization domain (NOD) proteins in
      C. jejuni recognition. We identified NOD1, but not NOD2, as a major PRR for C.
      jejuni in IEC. We also found that targeting intestinal epithelial NOD1 with small
      interfering RNA resulted in an increase in number of intracellular C. jejuni,
      thus highlighting a critical role for NOD1-mediated antimicrobial defence
      mechanism(s) in combating this infection at the gastrointestinal mucosal surface.

PMID- 17521328
TI  - How important are Toll-like receptors for antimicrobial responses?
AB  - The innate immune system is the primary line of defence against invading
      pathogenic microbes. Toll-like receptors (TLRs) are a family of membrane
      receptors which play a pivotal role in sensing a wide range of invading pathogens
      including bacteria, fungi and viruses. TLR-deficient mice have provided us with
      immense knowledge on the functioning of individual TLRs. Dysregulation of TLR
      signalling is linked with a number of disease conditions. Disease models have
      helped show that targeting components of TLR signalling cascades could lead to
      novel therapies in the treatment of infectious diseases. In this review we focus
      on the evidence provided to date to explain just how important TLRs are in host
      defence against microbial pathogens.

PMID- 17521329
TI  - Enterohaemorrhagic and enteropathogenic Escherichia coli Tir proteins trigger a
      common Nck-independent actin assembly pathway.
AB  - The Tir proteins of enterohaemorrhagic and enteropathogenic Escherichia coli
      (EHEC and EPEC respectively) are each translocated into the host plasma membrane
      where they promote F-actin pedestals in epithelial cells beneath adherent
      bacteria, but the two proteins act by different means. The canonical EPEC Tir
      becomes phosphorylated on tyrosine residue 474 (Y474) to recruit the host adaptor
      protein Nck, and also stimulates an inefficient, Nck-independent pathway
      utilizing tyrosine residue 454 (Y454). In contrast, the canonical EHEC Tir lacks
      Y474 and instead utilizes residues 452-463 to recruit EspF(U), an EHEC-specific
      effector that stimulates robust Nck-independent actin assembly. EHEC Tir Y458 and
      EPEC Tir Y454 are both part of an asparagine-proline-tyrosine (NPY) sequence. We
      report that each of the EHEC Tir NPY residues is required for EspF(U) recruitment
      and pedestal formation, and each of the EPEC Tir NPY residues is critical for
      inefficient, Nck-independent pedestal formation. Introduction of EspF(U) into
      EPEC dramatically enhanced Nck-independent actin assembly by EPEC Tir in a manner
      dependent on NPY(454). These results suggest that EPEC and EHEC Tir trigger a
      common Nck-independent actin assembly pathway and are both derived from an
      ancestral Tir molecule that utilized NPY to stimulate low-level pedestal
      formation.

PMID- 17521330
TI  - Characterization of the NADH:ubiquinone oxidoreductase (complex I) in the
      trypanosomatid Phytomonas serpens (Kinetoplastida).
AB  - NADH dehydrogenase activity was characterized in the mitochondrial lysates of
      Phytomonas serpens, a trypanosomatid flagellate parasitizing plants. Two
      different high molecular weight NADH dehydrogenases were characterized by native
      PAGE and detected by direct in-gel activity staining. The association of NADH
      dehydrogenase activities with two distinct multisubunit complexes was revealed in
      the second dimension performed under denaturing conditions. One subunit present
      in both complexes cross-reacted with the antibody against the 39 kDa subunit of
      bovine complex I. Out of several subunits analyzed by MS, one contained a domain
      characteristic for the LYR family subunit of the NADH:ubiquinone oxidoreductases.
      Spectrophotometric measurement of the NADH:ubiquinone 10 and NADH:ferricyanide
      dehydrogenase activities revealed their different sensitivities to rotenone,
      piericidin, and diphenyl iodonium.

PMID- 17521331
TI  - A new approach for distinguishing cathepsin E and D activity in antigen
      processing organelles.
AB  - Cathepsin E (CatE) and D (CatD) are the major aspartic proteinases in the
      endolysosomal pathway. They have similar specificity and therefore it is
      difficult to distinguish between them, as known substrates are not exclusively
      specific for one or the other. In this paper we present a substrate-based assay,
      which is highly relevant for immunological investigations because it detects both
      CatE and CatD in antigen-processing organelles. Therefore it could be used to
      study the involvement of these proteinases in protein degradation and the
      processing of invariant chain. An assay combining a new monospecific CatE
      antibody and the substrate, MOCAc-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(Dnp)-D
      Arg-NH2[where MOCAc is (7-methoxycoumarin-4-yl)acetyl and Dnp is dinitrophenyl],
      is presented. This substrate is digested by both proteinases and therefore can be
      used to detect total aspartic proteinase activity in biological samples. After
      depletion of CatE by immunoprecipitation, the remaining activity is due to CatD,
      and the decrease in activity can be assigned to CatE. The activity of CatE and
      CatD in cytosolic, endosomal and lysosomal fractions of B cells, dendritic cells
      and human keratinocytes was determined. The data clearly indicate that CatE
      activity is mainly located in endosomal compartments, and that of CatD in
      lysosomal compartments. Hence this assay can also be used to characterize
      subcellular fractions using CatE as an endosomal marker, whereas CatD is a well
      known lysosomal marker. The highest total aspartic proteinase activity was
      detected in dendritic cells, and the lowest in B cells. The assay presented
      exhibits a lower detection limit than common antibody-based methods without
      lacking the specificity.

PMID- 17521333
TI  - Alpha-D-mannopyranosyl-(1-->2)-alpha-D-glucopyranosyl-(1-->2)-glycerate in the
      thermophilic bacterium Petrotoga miotherma--structure, cellular content and
      function.
AB  - The intracellular accumulation of low molecular mass organic compounds in
      response to stressful conditions was investigated in the thermophilic bacterium
      Petrotoga miotherma, a member of the order Thermotogales. This led to the
      discovery of a new solute, whose structure was established as alpha-D
      mannopyranosyl-(1-->2)-alpha-D-glucopyranosyl-(1-->2)-glycerate (MGG) by MMR
      spectroscopy and MS. Under optimum growth conditions (3% NaCl; 55 degrees C), MGG
      was the major solute [up to 0.6 micromol.(mg protein)(-1)]; alpha-glutamate and
      proline were also present but in minor amounts [below 0.08 micromol.(mg protein)(
      1)]. The level of MGG increased notably with the salinity of the growth medium up
      to the optimum NaCl concentration. At higher NaCl concentrations, however, the
      level of MGG decreased, whereas the levels of proline and alpha-glutamate
      increased about five-fold and 10-fold, respectively. MGG plays a role during low
      level osmotic adaptation of Petrotoga miotherma, whereas alpha-glutamate and, to
      a lesser extent, proline are used for osmoprotection under salt stress. MGG is
      not part of the cell strategy for coping with heat or oxidative stress.
      Nevertheless, MGG was an efficient protector of pig heart malate dehydrogenase
      against heat inactivation and freeze-drying, although mannosylglycerate was
      better. This is the first report on the occurrence of MGG in living systems.

PMID- 17521332
TI  - Structure of Streptococcus agalactiae serine/threonine phosphatase. The subdomain
      conformation is coupled to the binding of a third metal ion.
AB  - We solved the crystal structure of Streptococcus agalactiae serine/threonine
      phosphatase (SaSTP) using a combination of single-wavelength anomalous dispersion
      phasing and molecular replacement. The overall structure resembles that of
      previously characterized members of the PPM/PP2C STP family. The asymmetric unit
      contains four monomers and we observed two novel conformations for the flap
      domain among them. In one of these conformations, the enzyme binds three metal
      ions, whereas in the other it binds only two. The three-metal ion structure also
      has the active site arginine in a novel conformation. The switch between the two-
      and three-metal ion structures appears to be binding of another monomer to the
      active site of STP, which promotes binding of the third metal ion. This
      interaction may mimic the binding of a product complex, especially since the
      motif binding to the active site contains a serine residue aligning remarkably
      well with the phosphate found in the human STP structure.

PMID- 17521334
TI  - Inhibition of an iron-responsive element/iron regulatory protein-1 complex by ATP
      binding and hydrolysis.
AB  - Iron regulatory protein-1 binding to the iron-responsive element of mRNA is
      sensitive to iron, oxidative stress, NO, and hypoxia. Each of these agents
      changes the level of intracellular ATP, suggesting a link between iron levels and
      cellular energy metabolism. Furthermore, restoration of iron regulatory protein-1
      aconitase activity after NO removal has been shown to require mitochondrial ATP.
      We demonstrate here that the iron-responsive element-binding activity of iron
      regulatory protein is ATP-dependent in HepG2 cells. Iron cannot decrease iron
      regulatory protein binding activity in cell extracts if they are simultaneously
      treated with an uncoupler of oxidative phosphorylation. Physiologic
      concentrations of ATP inhibit iron-responsive element/iron regulatory protein
      binding in cell extracts and binding of iron-responsive element to recombinant
      iron regulatory protein-1. ADP has the same effect, in contrast to the
      nonhydrolyzable analog adenosine 5'-(beta,gamma-imido)triphosphate, indicating
      that in order to inhibit iron regulatory protein-1 binding activity, ATP must be
      hydrolyzed. Indeed, recombinant iron regulatory protein-1 binds ATP with a Kd of
      86+/-17 microM in a filter-binding assay, and can be photo-crosslinked to azido
      ATP. Upon binding, ATP is hydrolyzed. The kinetic parameters [Km=5.3 microM,
      Vmax=3.4 nmol.min(-1).(mg protein)(-1)] are consistent with those of a number of
      other ATP-hydrolyzing proteins, including the RNA-binding helicases. Although the
      iron-responsive element does not itself hydrolyze ATP, its presence enhances iron
      regulatory protein-1's ATPase activity, and ATP hydrolysis results in loss of the
      complex in gel shift assays.

PMID- 17521335
TI  - The organotellurium compound ammonium trichloro(dioxoethylene-o,o')tellurate
      reacts with homocysteine to form homocystine and decreases homocysteine levels in
      hyperhomocysteinemic mice.
AB  - Ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) is an organotellurium
      compound with pleiotropic functions that has been associated with antitumoral,
      immunomodulatory and antineurodegenerative activities. Tellurium compounds with a
      +4 oxidation state, such as AS101, react uniquely with thiols, forming disulfide
      molecules. In light of this, we tested whether AS101 can react with the amino
      acid homocysteine both in vitro and in vivo. AS101 conferred protection against
      homocysteine-induced apoptosis of HL-60 cells. The protective mechanism of AS101
      against homocysteine toxicity was directly mediated by its chemical reactivity,
      whereby AS101 reacted with homocysteine to form homocystine, the less toxic
      disulfide form of homocysteine. Moreover, AS101 was shown here to reduce the
      levels of total homocysteine in an in vivo model of hyperhomocysteinemia. As a
      result, AS101 also prevented sperm cells from undergoing homocysteine-induced DNA
      fragmentation. Taken together, our results suggest that the organotellurium
      compound AS101 may be of clinical value in reducing total circulatory
      homocysteine levels.

PMID- 17521337
TI  - Cross-talk between the bone morphogenetic protein pathway and other major
      signaling pathways results in tightly regulated cell-specific outcomes.
AB  - Members of the bone morphogenetic protein (BMP) family of ligands have been
      identified in a variety of vertebrate and invertebrate species and have been
      shown to play an essential role in a range of biological processes, including
      mesodermal patterning and organ development, as well as the formation of bone and
      cartilage. Although the interaction of BMP ligands with specific type I and II
      serine-threonine kinase receptor complexes is crucial to the initiation of
      signaling, it is the interaction of intracellular signaling molecules, called
      Smads, with receptor complexes and other transcription factors that defines the
      repertoire of biological responses associated with the BMPs. But although all BMP
      ligands appear to interact with specific type I and II receptors, growing
      biochemical and developmental evidence supports the notion that alternative non
      Smad pathways also participates in BMP signaling. Here, we review the interaction
      or 'cross-talk' between the BMP and other major signaling pathways (transforming
      growth factor beta/activin, Notch, p38 mitogen-activated protein kinase and Toll)
      that results in tightly regulated cell-specific outcomes.

PMID- 17521338
TI  - Bone morphogenetic protein signaling in stem cells--one signal, many
      consequences.
AB  - Bone morphogenetic protein (BMP) signals play key roles throughout embryology,
      from the earliest patterning events, via tissue specification, through organ
      development and again in germ cell differentiation. While both input and the
      transducer molecules are rather well studied, the final outcome of a BMP signal
      is basically unpredictable and differs enormously between previously studied cell
      types. As already suggested by their name, BMPs exhibit most of their (known)
      functions on stem cells and precursor cells, usually driving them into various
      types of differentiation or death. In this minireview, some prime examples of BMP
      effects on several very different stem-cell types are discussed.

PMID- 17521339
TI  - Bone morphogenetic proteins in the early development of zebrafish.
AB  - Bone morphogenetic proteins (BMPs) are known to be widely involved in various
      biological processes. Many of the members of the BMP family, as well as related
      factors, receptors and molecules in the BMP signaling pathway, have been
      isolated, but their precise functions are still unclear. In addition to the
      'classical' model organism Xenopus, zebrafish, Danio rerio, is now considered to
      be a suitable model organism to study the roles of the BMP signaling pathway
      during embryogenesis. Mutagenesis screens have identified a number of mutants in
      the pathway. Although they do not cover the entire members of the BMP signaling
      cascade that are currently known, they serve as a powerful tool to broaden our
      understanding of BMP functions, in combination with other experimental
      techniques.

PMID- 17521340
TI  - Do recent seizures and recent changes in antiepileptic drugs impact performances
      on neuropsychological tests in subtle ways that might easily be missed?
AB  - PURPOSE: The possibility that a recent seizure or a recent change in
      antiepileptic medication might produce an occult change in neuropsychological
      performance is of interest, and especially so in the context of evaluation for
      epilepsy surgery. Such an evaluation is often done in a setting of video-EEG
      monitoring where a strong effort is made to produce seizures as quickly as
      possible with abrupt changes in medication, alterations in sleep, etc., which
      could impact the validity of neuropsychological findings. METHODS: A total of 126
      adults were studied who had seizures of strictly temporal origin (47 right, 79
      left) and whose recent medication history and seizure occurrence prior to testing
      was as clear as possible. All were tested with an extensive neuropsychological
      battery with great attention to giving tests only when the patients appeared
      clinically not to be suffering from recent seizures (seizures occurring on the
      day of testing or on the day prior to testing) or medication change effects. The
      cognitive correlates of side of seizures were also evaluated in order to provide
      a strength-of-effect comparison with recency of AED changes and seizures.
      RESULTS: Findings from three-way ANOVA showed a possible slight adverse effect of
      recent AED change, no effects of recent seizures, and a sizeable relationship
      with side of seizures. A simultaneous consideration of all three of these
      variables did not provide additional findings of interest. CONCLUSIONS: Although
      it is not possible to completely rule out some subtle cognitive effects of recent
      changes in medication or recent seizures, this investigation does not provide
      evidence for such effects when the neuropsychological evaluation is conducted
      carefully with no testing during any questionable or definite postictal periods.

PMID- 17521341
TI  - Dentate filter function is altered in a proepileptic fashion during aging.
AB  - PURPOSE: The elderly have an increased incidence and prevalence for seizure
      disorders. Further, since up to 50% of these cases have no identifiable
      antecedent, it has been hypothesized that aging of the central nervous system
      itself may be epileptogenic. Aged rats, compared to adults, exhibit a greater
      susceptibility to and severity of seizures associated with hippocampal
      activation. Whether this aging-related change reflects proconvulsive changes in
      limbic circuitry is unknown and thus was the focus of this study. METHODS:
      Hippocampal slices from adult and aged Fischer 344 rats were examined using
      electrophysiological techniques. The dentate gyrus was our model region since it
      is involved with both wet-dog shakes and limbic seizures, and it is affected
      preferentially with age. RESULTS: No differences were noted between groups in
      field potential activity elicited with low frequency stimulation. In contrast, 5
      Hz molecular layer stimulation could evoke multiple population spikes in
      approximately 40% of aged versus 0% of adult slices. Further, recording in CA3
      revealed that this stimulation paradigm could elicit multiple spikes in aged, but
      not adult, slices that frequently evolved into spontaneous epileptiform bursts.
      This change in the capacity of the dentate to respond to and filter afferent
      input was associated with an aging-related decrease in the frequency of
      spontaneous IPSPs and an increased propensity for large amplitude prolonged EPSPs
      following disinhibition. CONCLUSIONS: These epileptogenic changes in dentate
      function and circuitry could contribute to the exacerbated susceptibility for
      hippocampal seizures in aged rodents, as well as the aging-related decline in
      spatial learning and memory.

PMID- 17521342
TI  - Is photosensitive epilepsy less common in males due to variation in X chromosome
      photopigment genes?
AB  - Photosensitive epilepsy is less frequent among males than females. Red is the
      most epileptogenic color. The X-linked red pigment gene contains the polymorphism
      Ser180Ala; the Ser180 allele increases red sensitivity. We hypothesized that the
      paucity of males with photosensitive epilepsy is explained by the distribution of
      this sex-linked allele, and predicted photosensitive males would have a low
      frequency of this allele. We genotyped 35 males with photosensitive epilepsy and
      84 male controls. Allele frequencies did not differ between these groups. The
      hypothesis was not supported, so alternate reasons for the sex bias in
      photosensitive epilepsy must be sought.

PMID- 17521343
TI  - Seizure-free outcome in randomized add-on trials of the new antiepileptic drugs.
AB  - PURPOSE: The goal of this study is to (1) provide clinically useful, previously
      unpublished comparative analyses of seizure-freedom rates for newer antiepileptic
      drugs (AEDs), and (2) recommend a standard for data presentation and analysis.
      METHODS: Data were reviewed from placebo-controlled adjunctive trials in
      refractory patients of gabapentin (GPN), lamotrigine (LTG), topiramate (TOP),
      tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), zonisamide (ZNS), and
      pregabalin (PGB). Seizure-freedom analyses in these publications, if included at
      all, consistently included both patients who completed the trial, and those who
      dropped out prior to completion (last observation carried forward, LOCF). This
      has the potential to increase reported seizure-free outcomes. Pharmaceutical
      companies were contacted for the provision of unpublished seizure-free data in
      the patients who completed the entire study. RESULTS: In most cases, LOCF
      analysis produced a higher rate of seizure freedom compared to complete analysis.
      A total of 0%-1.1% of the LOCF population was seizure-free in the GPN trials
      (complete data not available). For the remaining AEDs, seizure-freedom results in
      the LOCF versus complete populations were: 0.7% versus 0.8% (LTG trial); 12%
      versus 2.6% (OXC trial); 3.6%-6.4% versus 3.9%-7.1% (LEV trial); 3.7%-7.9% versus
      1.3%-1.4% (PGB trial); and 6.0% versus 3.0% (ZNS trial, minus titration period).
      CONCLUSIONS: By employing LOCF, a clinically unrealistic picture of seizure-free
      rates may be reported. Access to complete data is informative, as it includes
      only those patients who were able to tolerate the drug at doses that produced
      seizure freedom. Ideally, data from both ITT and complete analyses should be made
      available.

PMID- 17521344
TI  - Glial activation links early-life seizures and long-term neurologic dysfunction:
      evidence using a small molecule inhibitor of proinflammatory cytokine
      upregulation.
AB  - PURPOSE: Early-life seizures increase vulnerability to subsequent neurologic
      insult. We tested the hypothesis that early-life seizures increase susceptibility
      to later neurologic injury by causing chronic glial activation. To determine the
      mechanisms by which glial activation may modulate neurologic injury, we examined
      both acute changes in proinflammatory cytokines and long-term changes in
      astrocyte and microglial activation and astrocyte glutamate transporters in a
      "two-hit" model of kainic acid (KA)-induced seizures. METHODS: Postnatal day (P)
      15 male rats were administered KA or phosphate buffered saline (PBS). On P45
      animals either received a second treatment of KA or PBS. On P55, control (PBS
      PBS), early-life seizure (KA-PBS), adult seizure (PBS-KA), and "two-hit" (KA-KA)
      groups were examined for astrocyte and microglial activation, alteration in
      glutamate transporters, and expression of the glial protein, clusterin. RESULTS:
      P15 seizures resulted in an acute increase in hippocampal levels of IL-1beta and
      S100B, followed by behavioral impairment and long-term increases in GFAP and
      S100B. Animals in the "two-hit" group showed greater microglial activation,
      neurologic injury, and susceptibility to seizures compared to the adult seizure
      group. Glutamate transporters increased following seizures but did not differ
      between these two groups. Treatment with Minozac, a small molecule inhibitor of
      proinflammatory cytokine upregulation, following early-life seizures prevented
      both the long-term increase in activated glia and the associated behavioral
      impairment. CONCLUSIONS: These data suggest that glial activation following early
      life seizures results in increased susceptibility to seizures in adulthood, in
      part through priming microglia and enhanced microglial activation. Glial
      activation may be a novel therapeutic target in pediatric epilepsy.

PMID- 17521345
TI  - Intravenous immunoglobulins in refractory childhood-onset epilepsy: effects on
      seizure frequency, EEG activity, and cerebrospinal fluid cytokine profile.
AB  - PURPOSE: Several studies have reported favorable effects of intravenous
      immunoglobulins (IVIG) in refractory epilepsy. Evidence substantiating an
      immunomodulatory action is scarce. In an open-label study, we prospectively
      investigated the effect of IVIG on clinical, EEG and serum/CSF immunological
      parameters in patients with refractory childhood-onset epilepsy. METHODS:
      Thirteen patients (median age 6.9 years; range 1.6-25.8) with refractory seizures
      despite 3-4 antiepileptic drug regimens were given IVIG (Sandoglobulin, ZLB
      Behring, add-on, 4 x 400 mg/kg/3 weeks). Seizure frequency, 24-h video-EEG, and
      CSF/serum immunological parameters and cytokine profiles (IL-6/IL-8/IL-12/IL-10)
      were documented before and after completion of the course. RESULTS: Seizure
      frequency was reduced by > or = 50% in four, and by 25%-50% in three patients. In
      contrast, variation in automatically recorded spike counts (1-h-wake and -sleep)
      did not correlate with clinical improvement. Serum immunological parameters
      showed variable deviations in eight patients (e.g., IgG(2) deficiency) and CSF
      immunoblotting showed oligoclonal bands in two patients. Blood-brain barrier
      permeability was normal in 12 patients. IL-6 and IL-8 were clearly detectable in
      CSF of all patients; the levels were significantly higher than those in plasma
      but remained unaffected by IVIG treatment. CONCLUSIONS: Despite unchanged EEG
      spike counts, substantial reductions in seizure frequency occurred in 7 of 13
      patients, suggesting that IVIG hinder progression of central epileptic activity
      into clinical seizures. Intrathecal presence of IL-8 and IL-6 was documented in
      all patients, but was unaffected by IVIG, suggesting that their production is
      directly related to electrical seizure activity and that IVIG may act through
      interference with immune pathways downstream to IL-6 and IL-8.

PMID- 17521346
TI  - Prolonged exposure to levetiracetam reveals a presynaptic effect on
      neurotransmission.
AB  - PURPOSE: The antiepileptic drug levetiracetam (LEV) is an enigma. Despite the
      fact that it specifically binds to the presynaptic vesicle protein, SV2A, no
      satisfactory mechanism of action has yet been identified. Using a combination of
      electrophysiological and cellular imaging techniques, we carefully tested the
      hypothesis that LEV directly interferes with neurotransmitter release. METHODS:
      We measured extracellular evoked responses in the CA1 region of rat hippocampal
      slices after paired pulse stimulation and after application of up to 10 pulses
      applied at 5-80 Hz. In parallel experiments, we used quantitative 2-photon
      microscopy and the fluorescent vesicular marker FM1-43 to measure the effect of
      repetitive stimulation on presynaptic vesicle release. RESULTS: Acute exposure to
      LEV (100 microM) had no effect on paired pulse synaptic responses. However, when
      slices were exposed to LEV for 3 h, there was a significant alteration in paired
      pulse responses and a more striking reduction in late synaptic potentials
      delivered in an 80 Hz train. LEV significantly reduced the rate of vesicle
      release assessed by FM1-43 destaining during 1 Hz stimulation. CONCLUSION: LEV is
      unique among currently available antiepileptics, because it directly inhibits
      presynaptic neurotransmitter release in a use-dependent fashion. While there are
      alternate explanations for this observation, it is plausible that LEV exerts its
      effect by binding to a protein selectively expressed in presynaptic nerve
      terminals.

PMID- 17521347
TI  - The antiepileptic drug levetiracetam stabilizes the human epileptic GABAA
      receptors upon repetitive activation.
AB  - PURPOSE: GABAA receptors from the brain of patients afflicted with mesial
      temporal lobe epilepsy (MTLE) become less efficient (run-down) when repetitively
      activated by GABA. Experiments were designed to investigate whether the
      antiepileptic drug, levetiracetam (LEV), which is used as an adjunctive treatment
      for medically intractable MTLE, counteracts the GABAA receptor run-down. METHODS:
      GABAA receptors were microtransplanted from the brains of patients afflicted with
      MTLE into Xenopus oocytes. The GABA-current run-down, caused by repetitive
      applications of GABA, was investigated using the standard two-microelectrode
      voltage-clamp technique. Additionally, the GABA-current run-down was investigated
      directly on pyramidal neurons in human MTLE cortical slices. RESULTS: It was
      found that, in oocytes injected with membranes isolated from the MTLE neocortex,
      the GABA-current run-down was inhibited by a 3-h pretreatment with 0.5-100 microM
      LEV. Moreover, the GABAA receptors of pyramidal neurons in human neocortical
      slices exhibited a current run-down that was significantly reduced by 1 microM
      LEV. Interestingly, the run-down in oocytes injected with membranes isolated from
      the MTLE hippocampal subiculum was not affected by LEV. CONCLUSIONS: We report
      that the antiepileptic LEV strengthens GABA inhibition of neuronal circuits by
      blocking the receptor run-down in the cortex whilst leaving the run-down of GABAA
      receptors in the hippocampal subiculum unaltered. These findings point to the
      GABAA receptor run-down as an important event in epileptogenesis and as a
      possible target for testing and screening antiepileptic drugs.

PMID- 17521348
TI  - Maternal epilepsy and offsprings' adult intelligence: a population-based study
      from Norway.
AB  - PURPOSE: We examined if children of mothers with epilepsy had normal
      intelligence, speculating that either epilepsy or its therapy might affect this
      parameter. METHODS: In a population-based cohort study in Norway, information on
      maternal epilepsy reported to the Medical Birth Registry of Norway, 1967-1979 was
      linked to information on 18-19-year-old men's intellectual ability and
      anthropometric measures ascertained by the Norwegian Conscripts Service, 1984
      1999. The standardized intelligence test (IQ score) was reported as single-digit
      standard scores with values from 1 to 9. No individual information on
      antiepileptic drug therapy was available. RESULTS: Mean IQ score was lower in
      1,207 conscripts whose mothers had epilepsy reported on the birth notification
      form, as compared with 316,554 conscripts of mothers without epilepsy; 4.8
      (standard deviation 1.8) versus 5.2(1.8), p < 0.001, respectively. This
      difference remained after adjustment for maternal education, maternal age, birth
      order, marital status, year of birth, and weight and length at birth. When
      comparing men with and without reported maternal epilepsy, the odds ratio of
      having an IQ score < or = 3 was 1.6 (95% confidence interval: 1.4-1.8), which was
      unaffected by adjustment for confounding factors. Mean height among conscripts of
      mothers with and without epilepsy measured 178.6 and 179.9 cm, respectively, a
      difference of 1.3 cm (p < 0.001). CONCLUSIONS: We observed that almost 20 years
      after birth, maternal epilepsy was associated with reduced IQ score and also
      shorter adult height in male offspring. We do not know whether these findings
      will persist when epilepsy is better treated with the newer and safer generation
      of antiepileptic drugs.

PMID- 17521350
TI  - Analysis of a quantitative trait locus for seizure susceptibility in mice using
      bacterial artificial chromosome-mediated gene transfer.
AB  - PURPOSE: Previous quantitative trait loci (QTL) mapping studies from our
      laboratory identified a 6.6 Mb segment of distal chromosome 1 that contains a
      gene (or genes) having a strong influence on the difference in seizure
      susceptibility between C57BL/6 (B6) and DBA/2 (D2) mice. A gene transfer strategy
      involving a bacterial artificial chromosome (BAC) DNA construct that contains
      several candidate genes from the critical interval was used to test the
      hypothesis that a strain-specific variation in one (or more) of the genes is
      responsible for the QTL effect. METHODS: Fertilized oocytes from a seizure
      sensitive congenic strain (B6.D2-Mtv7a/Ty-27d) were injected with BAC DNA and
      three independent founder lines of BAC-transgenic mice were generated. Seizure
      susceptibility was quantified by measuring maximal electroshock seizure threshold
      (MEST) in transgenic mice and nontransgenic littermates. RESULTS: Seizure testing
      documented significant MEST elevation in all three transgenic lines compared to
      littermate controls. Allele-specific RT-PCR analysis confirmed gene transcription
      from genome-integrated BAC DNA and copy-number-dependent phenotypic effects were
      observed. CONCLUSIONS: Results of this study suggest that the gene(s) responsible
      for the major chromosome 1 seizure QTL is found on BAC RPCI23-157J4 and
      demonstrate the utility of in vivo gene transfer for studying quantitative trait
      genes in mice. Further characterization of this transgenic model will provide new
      insight into mechanisms of seizure susceptibility.

PMID- 17521349
TI  - Age-dependent seizure semiology in temporal lobe epilepsy.
AB  - OBJECTIVE: To examine the effects of age on different aspects of temporal lobe
      seizure semiology. METHODS: We performed a video analysis of 605 archived
      seizures from 155 consecutive patients (age 10 months to 49 years) selected by
      seizure freedom after temporal lobectomy. Eighty patients had hippocampal
      sclerosis (HS). Beside semiological seizure classification, we assessed age
      dependency of several axes of seizure semiology: (1) aura, (2) number of
      different lateralizing signs, occurrence of ictal (3) emotional signs, (4)
      autonomic symptoms, (5) automatisms, and (6) secondary generalization as well as
      (7) the ratio of motor seizure components. RESULTS: From the 155 patients, 117
      reported aura, 39 had ictal emotional signs, 51 had autonomic symptoms, 130
      presented automatisms, while 18 patients showed secondary generalization at least
      once during their seizures. Altogether 369 (median: 2/patient) different
      lateralizing signs were recorded. Frequency of HS (p < 0.001), ictal automatisms
      (p < 0.001), secondary generalization (p = 0.014), number of different
      lateralizing signs (p < 0.001) increased while the ratio of motor seizure
      component (p = 0.007) decreased by age. Auras, emotional symptoms, and autonomic
      signs occurred independently of patients' ages. Hippocampal sclerosis adjusted
      linear models revealed that the frequency of automatisms and secondarily
      generalized seizures as well as the number of different lateralizing signs are HS
      independent significant variables. CONCLUSION: Our findings support that brain
      maturation significantly influences the evolution of some important aspects
      (motor seizures, lateralizing signs) of temporal lobe seizure semiology.
      Conversely, other aspects (aura, emotional, and autonomic signs) are independent
      of the maturation process. This is the first report investigating age dependency
      of epileptic seizure semiology comparing all age groups.

PMID- 17521352
TI  - Can evidence-based guidelines and clinical trials tell us how to treat patients?

PMID- 17521353
TI  - A large-scale mutagenesis screen to identify seizure-resistant zebrafish.
AB  - PURPOSE: Zebrafish are a vertebrate organism ideally suited to mutagenesis
      screening strategies. Although a genetic basis for seizure susceptibility and
      epilepsy is well established, no efforts have been made to study seizure
      resistance. Here we describe a novel strategy to isolate seizure-resistant
      zebrafish mutants from a large-scale mutagenesis screen. METHODS: Seizures were
      induced with pentylenetetrazole (PTZ). Zebrafish were analyzed between 3 and 7
      days postfertilization (dpf). Genome mutations were induced in founders by using
      N-ethyl-nitrosourea (ENU). Seizure behavior was monitored by using a high-speed
      camera and quantified by locomotion-tracking software. Electrographic activity
      was monitored by using a field-recording electrode placed in the optic tectum of
      agar-immobilized zebrafish. RESULTS: Short-term PTZ exposure elicited a burst
      suppression seizure pattern in 3-dpf zebrafish and more complex activity
      consisting of interictal- and ictal-like discharges at 7 dpf. Prolonged exposure
      to PTZ induced status epilepticus-like seizure activity and fatality in wild-type
      zebrafish larvae. With a PTZ survival assay at 6-7 dpf, we identified six
      zebrafish mutants in a forward-genetic screen covering nearly 2,000 F(2)
      families. One mutant (s334) also was shown to exhibit reduced behavioral activity
      on short-term PTZ exposure and an inability to generate long-duration ictal-like
      discharge. CONCLUSIONS: Zebrafish offers a powerful tool for the identification
      and study of a genetic basis for seizure resistance.

PMID- 17521354
TI  - Potential role of thiol:disulfide oxidoreductases in the pathogenesis of
      Helicobacter pylori.
AB  - Helicobacter pylori infections are responsible for a sequence of molecular events
      which ultimately result in the development of gastric diseases. The pathogenesis
      of H. pylori has been studied extensively with strong focus on the identification
      of virulence factors. In contrast, the involvement of thiol:disulfide
      oxidoreductases in bacterial pathogenesis is less well understood. This paper
      provides a review of the current knowledge of H. pylori putative thiol:disulfide
      oxidoreductases, and their potential role in promoting virulence and
      colonization. Several bioinformatic analyses served to complete the information
      on these oxidoreductases of H. pylori.

PMID- 17521355
TI  - The neutrophil-activating protein of Helicobacter pylori (HP-NAP) as an immune
      modulating agent.
AB  - During evolution microorganisms have developed several immune modulating
      strategies. The Helicobacter pylori neutrophil-activating protein (HP-NAP) is a
      virulence factor that attracts and activates neutrophils, and promotes their
      endothelial adhesion and the production of oxygen radicals and chemokines,
      including CXCL8, CCL3 and CCL4. HP-NAP, a TLR2 agonist, is an immune modulator
      able to induce the expression of interleukin-12 (IL-12) and IL-23 by human
      neutrophils and monocytes. In fact, HP-NAP has the potential to shift antigen
      specific T-cell responses from a predominant Th2 to a polarized Th1 cytotoxic
      phenotype, characterized by high levels of interferon-gamma and tumor necrosis
      factor-alpha production. Thus, HP-NAP is a key factor driving Th1 inflammation in
      H. pylori infection and may be a new tool for future therapeutic strategies aimed
      at redirecting Th2 into Th1 responses, for example in atopy, vaccinology and
      cancer immunotherapy.

PMID- 17521356
TI  - Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori
      infection.
AB  - Helicobacter pylori is an important pathogen in major gastroduodenal diseases,
      including inflammation with ulceration and gastric malignancies. Alterations in
      H. pylori associated cell turnover in gastric epithelial cells are examined in
      relation to inflammatory activity, bacteria load and cytokines which may improve
      knowledge concerning the outcome of gastric diseases caused by H. pylori. Antral
      biopsies from 42 dyspeptic patients including 27 H. pylori-positive and 15 H.
      pylori-negative patients were tested for apoptotic activity by the TUNEL assay,
      and immuno-histochemically for p53 and the proliferative marker Ki-67. H. pylori
      infection, bacteria load and inflammatory activity were associated with increased
      cell turnover as judged by enhanced activities of TUNEL, p53 and Ki-67. Only p53
      was significantly correlated to IFN-gamma, IL-8 and IL-10. The H. pylori-positive
      state was furthermore accompanied by varying degrees of altered distribution
      pattern of the markers studied, with occasional presence of apoptosis in the
      deeper pit zones, upward extension of Ki-67 and to a lesser degree of p53. Given
      a similar pattern of change in proliferation and apoptosis in some neoplastic
      lesions in other parts of the gastrointestinal tract, such studies in cell
      turnover may provide insights valuable in the investigations of potential
      precursors of gastric malignancies.

PMID- 17521357
TI  - Antiadhesive property of microalgal polysaccharide extract on the binding of
      Helicobacter pylori to gastric mucin.
AB  - The emergence of antibiotic-resistant Helicobacter pylori is of concern in the
      treatment of H. pylori-associated gastroduodenal diseases. As the organism was
      reported to bind gastric mucin, we used porcine gastric mucin as substrate to
      assess the antiadhesive property of polysaccharides derived from Spirulina (PS),
      a commercially available microalga, against the binding of H. pylori to gastric
      mucin. Results show that polysaccharides prevented H. pylori from binding to
      gastric mucin optimally at pH 2.0, without affecting the viability of either
      bacteria or gastric epithelial cells, thus favouring its antiadhesive action in a
      gastric environment. Using ligand overlay analysis, polysaccharide was
      demonstrated to bind H. pylori alkyl hydroperoxide reductase (AhpC) and urease,
      which have shown here to possess mucin-binding activity. An in vivo study
      demonstrated that bacteria load was reduced by >90% in BALB/c mice treated with
      either Spirulina or polysaccharides. It is thus suggested that polysaccharides
      may function as a potential antiadhesive agent against H. pylori colonization of
      gastric mucin.

PMID- 17521358
TI  - Xanthomonas caspase displays an inherent PARP-like activity.
AB  - In an earlier study, intracellular accumulation of metabolites such as pyruvate
      and citrate in Xanthomonas campestris pv. glycines (Xcg) was found to result in a
      caspase dependent stationary phase rapid cell death (RCD). In the present study,
      the presence of poly ADP-ribose polymerase (PARP)-like activity associated with
      caspase-3-like protein of Xcg is reported. This activity was found to be
      responsible for depletion of cellular NAD(+) levels in RCD-promoting media such
      as Luria-Bertani medium and starch medium fortified with citrate. Addition of
      PARP-specific inhibitors such as 3-aminobenzamide to RCD-promoting media restored
      the intracellular NAD(+) levels and thereby prevented RCD. The inherent
      association of PARP-like activity with the caspase protein was demonstrated by
      PARP cellular assay, immuno-precipitation and Western analysis. A truncated
      polysaccharide deacetylase gene having a caspase-like domain was cloned. The
      expressed protein though found to be inactive, cross-reacted with human caspase
      and PARP antibodies. This is the first report demonstrating the presence of a
      PARP-like activity in a prokaryote and its involvement in cell death.

PMID- 17521359
TI  - Genetic characterization of Vibrio cholerae strains by inter simple sequence
      repeat-PCR.
AB  - The utility of inter simple sequence repeat-PCR (ISSR-PCR) assay in the
      characterization and elucidation of the phylogenetic relationship between the
      pathogenic and nonpathogenic isolates of Vibrio cholerae is demonstrated. A total
      of 45 V. cholerae strains including 15 O1 El Tor, nine O139 and 21 non-O1/non
      O139 strains were analyzed using eight ISSR primers. These primers, which are
      essentially simple sequence repeats (SSR) with additional nonrepeat bases at the
      5' or 3' end, amplify genomic regions interspersed between closely spaced SSRs.
      Neighbor-joining analysis showed that the strains belonging to the same serogroup
      clustered together with the exception of one O1 and two O139 strains. The absence
      of pathogenicity islands in these strains, as confirmed by PCR, suggested their
      non-O1/non-O139 origin. Thus the ISSR-PCR-based phylogeny was consistent with the
      classification of V. cholerae based on serological methods. A finer resolution of
      the clustering of the toxinogenic O1 El Tor and toxinogenic O139 subtypes was
      obtained by ISSR-PCR analysis as compared with the Enterobacterial Repetitive
      Intergenic Consensus sequences-based PCR analysis for the same set of strains.
      Thus, it is proposed that ISSR-PCR is an efficient tool in phylogenetic
      classification of prokaryotic genomes in general and diagnostic genotyping of
      microbial pathogens in particular.

PMID- 17521360
TI  - Attachment of bacteria to the roots of higher plants.
AB  - Attachment of soil bacteria to plant cells is supposedly the very early step
      required in plant-microbe interactions. Attachment also is an initial step for
      the formation of microbial biofilms on plant roots. For the rhizobia-legume
      symbiosis, various mechanisms and diverse surface molecules of both partners have
      been proposed to mediate in this process. The first phase of attachment is a
      weak, reversible, and unspecific binding in which plant lectins, a Ca(+2)-binding
      bacterial protein (rhicadhesin), and bacterial surface polysaccharide appear to
      be involved. The second attachment step requires the synthesis of bacterial
      cellulose fibrils that cause a tight and irreversible binding of the bacteria to
      the roots. Cyclic glucans, capsular polysaccharide, and cellulose fibrils also
      appear to be involved in the attachment of Agrobacterium to plant cells.
      Attachment of Azospirillum brasilense to cereals roots also can be divided in two
      different steps. Bacterial surface proteins, capsular polysaccharide and flagella
      appear to govern the first binding step while extracellular polysaccharide is
      involved in the second step. Outer cell surface proteins and pili are implicated
      in the adherence of Pseudomonas species to plant roots.

PMID- 17521361
TI  - Two distinct manganese-containing superoxide dismutase genes in Bacillus cereus:
      their physiological characterizations and roles in surviving in wheat
      rhizosphere.
AB  - Rhizosphere inhabitants interact intricately with plant host. Bacillus cereus 905
      isolated from wheat rhizosphere colonized wheat rhizosphere with large population
      size. In this work, the role of superoxide dismutases (SODs) of B. cereus 905 in
      surviving in wheat rhizosphere was analyzed. Two genes, sodA-1 and sodA-2
      encoding two distinct manganese SODs (MnSODs), were isolated from the bacterium.
      The amino acid sequence similarity between the two peptides is 58.43%. Through
      homologous recombination, three mutant strains have been created, each lacking
      either sodA-1, sodA-2 or both. Analysis of these mutant strains revealed
      differences in transcription and enzymatic activity of SOD. MnSOD2, encoded by
      sodA-2, plays a more important role in antioxidative stress. MnSOD1, the product
      of sodA-1 gene, is expressed at lower level. The function of the two MnSODs
      appears to be essential in colonization of wheat rhizosphere.

PMID- 17521362
TI  - Development of species-specific primers for detection of Streptococcus mutans in
      mixed bacterial samples.
AB  - Streptococcus mutans is the major microbial pathogen associated with dental
      caries in children. The objectives of this study were to design and evaluate
      species-specific primers for the identification of S. mutans. Validation of the
      best primer set, Sm479F/R, was performed using seven S. mutans reference strains,
      48 ATCC non-S. mutans strains, 92 S. mutans clinical isolates, DNA samples of S.
      mutans-Streptococcus sobrinus or S. mutans-Streptococcus sanguinis, and mixed
      bacterial DNA of saliva samples from 33 18-month-old children. All of the S.
      mutans samples tested positive, and no PCR products were amplified from members
      of the other streptococci or nonstreptococci strains examined. The lowest
      detection level for PCR was 10(-2) ng of S. mutans DNA (c. 4.6 x 10(3) copies) in
      the test samples. The results of this study suggest that the Sm479F/R primer pair
      is highly specific and sensitive for identification of S. mutans in either
      purified or mixed DNA samples.

PMID- 17521363
TI  - Intimin subtyping of Escherichia coli: concomitant carriage of multiple intimin
      subtypes from forage-fed cattle and sheep.
AB  - The outer membrane protein, intimin (eae), which mediates bacterial attachment to
      epithelial cells, is associated with enteropathogenic Escherichia coli and some
      Shiga toxin-producing E. coli. The eae subtype of E. coli strains isolated from
      healthy cattle and sheep was identified using a rapid PCR-restriction fragment
      length polymorphism (RFLP) method to produce profiles that were compared with
      those generated in silico. The 139 eae-positive E. coli strains were separated
      into 11 different PCR-RFLP profiles. The most common eae PCR-RFLP type was beta
      (23.7%), followed by zeta (20.1%), theta (16.5%), iota (12.2%), kappa (8.6%),
      epsilon (7.2%), gamma (2.9%), nu and beta2 (2.2%) and iota2 (1.4%). Four isolates
      did not yield a PCR-RFLP amplification product but complete sequencing of the eae
      gene matched subtype rho. Two different eae variants were isolated from the same
      swab from 18 different animals and subtype iota was the most 'promiscuous', being
      isolated with four other eae subtypes from seven separate animals. None of the
      eae-positive STEC were subtype gamma, which is associated with STEC serogroup
      O157. This method allowed the rapid identification of eae subtypes and indicates
      that forage-fed animals possessed a wide diversity of bacterial eae subtypes with
      a low frequency of eae subtype gamma.

PMID- 17521364
TI  - Evaluation of major membrane protein-II as a tool for serodiagnosis of leprosy.
AB  - As serodiagnosis is the easiest way of diagnosing a disease, the utility of
      Mycobacterium leprae-derived major membrane protein-II (MMP-II), one of the
      immuno-dominant antigens, in the serodiagnosis of leprosy was examined. The
      percent positivity by an enzyme-linked immunosorbent assay for anti-MMP-II
      antibody was 82.4% for multi-bacillary leprosy, and the specificity of the test
      was 90.1%. For pauci-bacillary leprosy where cell-mediated immunity predominates,
      39.0% showed positive results. These percentage values were significantly higher
      than these values obtained for existing phenolic glycolipid-I based methods,
      suggesting that MMP-II antibody detection would facilitate the diagnosis of
      leprosy.

PMID- 17521365
TI  - Identification of a new gene PA5017 involved in flagella-mediated motility,
      chemotaxis and biofilm formation in Pseudomonas aeruginosa.
AB  - Flagella-mediated motility is recognized as one of the major factors contributing
      to virulence in Pseudomonas aeruginosa. During a screening of a mini-Mu
      transposon mutant library of P. aeruginosa PA68, a mutant partially deficient in
      swimming and swarming motility was identified in a new locus that encodes a
      predicted protein of unknown function annotated PA5017 in the P. aeruginosa PAO1
      genome sequence. Chemotaxis plate assay indicated that inactivation of the PA5017
      gene led to a decreased chemotactic response. Complementation of the PA5017
      mutant with the wild-type PA5017 gene restored normal motility and chemotaxis
      phenotype. A promoter-lacZ reporter activity assay of the cheYZAB operon from
      chemotaxis gene cluster 1 showed that there was almost a twofold difference in
      expression levels of the wild-type PA68 and the PA5017 mutant. This suggested
      that the PA5017 affected expression of the cheYZAB operon negatively. Further
      study showed that inactivation of the PA5017 gene in PA68 led to increased
      biofilm formation in a static system and to the formation of a heterogeneous
      biofilm in a flow-chamber system. These results suggested that PA5017 possibly
      affected flagellum-dependent motility and in turn biofilm formation via the
      chemotaxis signal transduction pathway.

PMID- 17521366
TI  - Infection-induced antibodies against the major outer membrane protein of
      Campylobacter jejuni mainly recognize conformational epitopes.
AB  - The major outer membrane protein (MOMP) of Campylobacter jejuni is an abundant
      surface protein with a pore-forming function and may be a potential candidate for
      vaccine development. Despite the fact that MOMP is immunogenic and the
      recombinant MOMP (rMOMP) can be readily produced in Escherichia coli, the nature
      of the antibody response to MOMP during in vivo infection is not well understood.
      In this study, various methods involving detergent replacement and liposome
      reconstitution were used to refold rMOMP, and antibody responses to MOMP elicited
      in Campylobacter-colonized chickens were evaluated using sera from chickens
      either naturally or experimentally infected by C. jejuni. The results
      demonstrated that proteoliposomes restored the reactivity of rMOMP to rabbit
      antibodies elicited by native MOMP, indicating the recovery of native MOMP
      conformation by this refolding method. Importantly, sera from naturally or
      experimentally infected chickens reacted weakly with denatured rMOMP, but
      strongly with rMOMP reconstituted in proteoliposome, suggesting that the chicken
      antibody response to MOMP is predominantly directed against conformational
      epitopes. These observations provide direct evidence for conformation-dependent
      humoral responses to MOMP induced by Campylobacter infection, demonstrate that C.
      jejuni MOMP is immunogenic in its natural host and suggest that proteoliposomes
      may be potentially used for the evaluation of rMOMP-based vaccines.

PMID- 17521367
TI  - Epigenetic profile of testicular germ cell tumours.
AB  - DNA methylation is the best known and most thoroughly studied epigenetic
      mechanism. Hypermethylation of CpG islands associated with silencing of tumour
      suppressor genes or tumour-related genes is a common hallmark of human cancer.
      The list of tumour-related genes with aberrant hypermethylation in their CpG
      islands has been increasing. There is also the potential for using DNA
      methylation profile data as markers for various types of human cancer. In this
      paper, we review the methylation profile of testicular germ cell tumours (TGCTs).
      We show that TGCTs have distinctive DNA methylation profiles that differ from
      those of somatic tissue-derived cancers or somatic tissues. We also discuss the
      methylation profile of TGCTs in terms of the DNA reprogramming that occurs in
      primordial germ cells or pre-implantation embryos. Finally, we describe the
      potential clinical utility of this unique methylation phenotype in TGCTs with
      regard to developing a novel tumour marker. These data suggest that unmethylated
      DNA fragments in TGCTs may have diagnostic implications. Further elucidation of
      epigenetic profiles in TGCTs is expected to provide a new insight into the
      biology of this disease.

PMID- 17521368
TI  - Mannose-binding lectin without the aid of its associated serine proteases alters
      lipopolysaccharide-mediated cytokine/chemokine secretion from human endothelial
      cells.
AB  - Coupling between certain pathogen-associated molecular patterns and corresponding
      pattern recognition receptors of endothelial cells is important for the mediation
      of vascular inflammatory responses. Mannose-binding lectin (MBL) recognizes
      certain carbohydrate structures of microbes and subsequently activates the
      complement system as well as facilitates the phagocytosis of targets. We
      investigated whether MBL can intervene in the interaction between bacterial
      lipopolysaccharide (LPS) and endothelial cells to modulate subsequent
      inflammatory responses. In response to LPS, human umbilical vein endothelial
      cells (HUVEC) produced various cytokines/chemokines. Addition of the purified
      human MBL/MBL-associated serine proteases (MASP) complex or recombinant human MBL
      enhanced LPS-mediated cytokine/chemokine secretion by HUVEC, including
      interleukin-8 (IL-8), IL-6 and monocyte chemoattractant protein-1 in a dose
      dependent manner. This enhancing effect was ameliorated by the addition of anti
      MBL antibody or mannan. Among the cytokines/chemokines we analysed, IL-6 showed
      the greatest increase of secretion in the presence of native MBL/MASP complex or
      recombinant MBL. MBL, regardless of its association with MASP, alters LPS
      mediated cytokine/chemokine secretion of HUVEC. Besides the well-known functions
      of MBL, to activate the lectin-complement pathway and to facilitate clearance of
      targets, alteration of cytokine/chemokine secretion may provide an additional
      role for MBL in modulating vascular inflammation.

PMID- 17521369
TI  - The delivery site of a monovalent influenza vaccine within the respiratory tract
      impacts on the immune response.
AB  - Pulmonary vaccination is a promising immunization route. However, there still
      remains a crucial need to characterize the different parameters affecting the
      efficacy of inhaled vaccination. This study aimed at assessing the impact of
      antigen distribution within the respiratory tract on the immune response to a
      monovalent A/Panama/2007/99 H3N2 influenza split virus vaccine administered to
      BALB/c mice. Varying the administration technique allowed the targeting of the
      vaccine to different sites of the mouse respiratory tract, i.e. the nasal cavity,
      the upper or central airways, or the deep lung. This targeting was verified by
      using ovalbumin as a tracer compound. The immune responses generated following
      influenza vaccine administration to the different respiratory tract sites were
      compared to each other and to those elicited by intramuscular and peroral
      intragastric immunization. Delivery of the vaccine to the different respiratory
      regions generated systemic, local and cellular virus-specific immune responses,
      which increased with the depth of vaccine deposition, culminating in deep-lung
      vaccination. The latter induced virus-specific serum immunoglobulin G and
      neutralizing antibody titres as elevated as intramuscular vaccination, whereas
      the production of mucosal secretory immunoglobulin A was significantly superior
      in deep-lung-vaccinated animals. The analysis of cytokines secreted by
      mononuclear cells during an in vitro recall response indicated that deep-lung
      vaccination induced a local shift of the cellular immune response towards a T
      helper type 1 phenotype as compared to intramuscular vaccination. In conclusion,
      antigen distribution within the respiratory tract has a major effect on the
      immune response, with the deep lung as the best target for inhaled influenza
      vaccination.

PMID- 17521370
TI  - Janus kinase 3-deficient T lymphocytes have an intrinsic defect in CCR7-mediated
      homing to peripheral lymphoid organs.
AB  - Chemokine-mediated signalling involves the activation of a Janus kinase (Jak)
      pathway. We have previously shown that Jak3 mediates CCR9 and CXCR4 signalling in
      response to CCL25 and CXCL12 in BM progenitors and thymocytes. The lack of
      peripheral lymph nodes and Peyer's patches observed in Jak3(-/-) mice suggested a
      possible role of Jak3 in CCR7-mediated homing to these organs. Here, we
      demonstrate phosphorylation of Jak3 in peripheral lymphocytes in response CCL19
      and CCL21. In addition, Jak3(-/-) naive T cells and pharmacologically inhibited
      Jak3(+/+) T lymphocytes have impaired chemotactic responses towards these
      ligands. Interestingly, CCR7 expression was higher in Jak3(-/-) thymocytes
      compared to their Jak3(+)(/-) littermates, indicating that the impaired migration
      must be caused by impaired CCR7-mediated signalling, in the absence of Jak3. In
      addition, adoptive transfer experiments showed that Jak3(+/+) mice reconstituted
      with Jak3(-/-) green fluorescent protein (GFP)(+) bone marrow progenitors had
      reduced T-lymphocyte homing to peripheral and mesenteric lymph nodes, compared to
      reconstitution with Jak3(+/+) GFP(+) progenitors. Furthermore, reciprocal
      transfer experiments indicated that Jak3(-/-) stromal cells were not responsible
      for the deficient T-cell homing. Finally, we performed direct competitive homing
      assays and demonstrated that Jak3(-/-) T lymphocytes have a clear defect in
      homing to peripheral and mesenteric lymph nodes, while migration to spleen was
      moderately impaired. Our data demonstrates that Jak3(-/-) T lymphocytes have an
      intrinsic defect in CCR7-mediated homing to peripheral lymphoid organs.

PMID- 17521371
TI  - Activating and inhibitory receptors on synovial fluid natural killer cells of
      arthritis patients: role of CD94/NKG2A in control of cytokine secretion.
AB  - Natural killer (NK) cells are activated early during inflammatory events and
      contribute to the shaping of the ensuing adaptive immune response. To further
      understand the role for NK cells in inflammation, we investigated the phenotype
      and function of synovial fluid (SF) NK cells from patients with chronic joint
      inflammation, as well as from patients with transient inflammation of the knee
      following trauma. We confirm that synovial NK cells are similar to the well
      characterized CD56(bright) peripheral blood (PB) NK-cell subset present in
      healthy individuals. However, compared to this PB subset the synovial NK cells
      express a higher degree of activation markers including CD69 and NKp44, the
      latter being up-regulated also on CD56(bright) NK cells in the PB of patients.
      Activated synovial NK cells produced interferon-gamma and tumour necrosis factor,
      and the production was further up-regulated by antibody masking of CD94/NKG2A,
      and down-regulated by target cells expressing human leucocyte antigen-E in
      complex with peptides known to engage CD94/NKG2A. We conclude that synovial NK
      cells have an activated phenotype and that CD94/NKG2A is a key regulator of
      synovial NK-cell cytokine synthesis.

PMID- 17521372
TI  - Downregulation of Fes inhibits VEGF-A-induced chemotaxis and capillary-like
      morphogenesis by cultured endothelial cells.
AB  - The aim of this study was to determine whether the downregulation of endogenous
      Fes by siRNA in cultured endothelial cells affects vascular endothelial growth
      factor-A (VEGF-A)-induced chemotaxis and capillary-like morphogenesis, which are
      considered as angiogenic cellular responses in vitro. VEGF-A-treatment induced
      autophosphorylation of Fes in cultured endothelial cells. LY294002, a
      phosphoinositide 3-kinase inhibitor, significantly inhibited VEGF-A-induced
      chemotaxis and capillary-like morphogenesis. Downregulation of Fes attenuated
      these VEGF-A-induced cellular responses but LY294002 did not produce further
      inhibition of these responses. Downregulation of Fes neither affected VEGF-A
      induced autophosphorylation of VEGF receptor 2 nor mitogen-activated protein
      kinase activation, but markedly decreased Akt activation. Taken together, our
      novel results indicate the involvement of Fes in VEGF-A-induced cellular
      responses by cultured endothelial cells.

PMID- 17521374
TI  - Polysomnographically measured sleep abnormalities in PTSD: a meta-analytic
      review.
AB  - Although sleep complaints are common among patients with Posttraumatic stress
      disorder (PTSD), polysomnographic studies examining sleep abnormalities in PTSD
      have produced inconsistent results. To clarify discrepant findings, we conducted
      a meta-analytic review of 20 polysomnographic studies comparing sleep in people
      with and without PTSD. Results showed that PTSD patients had more stage 1 sleep,
      less slow wave sleep, and greater rapid-eye-movement density compared to people
      without PTSD. We also conducted exploratory analyses aimed at examining potential
      moderating variables (age, sex, and comorbid depression and substance use
      disorders). Overall, studies with a greater proportion of male participants or a
      low rate of comorbid depression tended to find more PTSD-related sleep
      disturbances. These findings suggest that sleep abnormalities exist in PTSD, and
      that some of the inconsistencies in prior findings may be explained by moderating
      variables.

PMID- 17521373
TI  - Immunopathology and molecular diagnosis of autoimmune bullous diseases.
AB  - Autoimmune bullous diseases are associated with autoimmunity against structural
      components maintaining cell-cell and cell matrix adhesion in the skin and mucous
      membranes. Pemphigus diseases are characterized by autoantibodies against the
      intercellular junctions and intraepithelial blisters. In pemphigoid diseases and
      epidermolysis bullosa acquisita, sub-epidermal blistering is associated with
      autoantibodies targeting proteins of the hemidesmosomal anchoring complex. The
      autoantigens in autoimmune blistering diseases have been extensively
      characterized over the past three decades. In general, the pathogenicity of
      autoantibodies, already suggested by clinical observations, has been conclusively
      demonstrated experimentally. Detection of tissue-bound and circulating serum
      autoantibodies and characterization of their molecular specificity is mandatory
      for the diagnosis of autoimmune blistering diseases. For this purpose, various
      immunofluorescence methods as well as immunoassays, including immunoblotting,
      enzyme-linked immunosorbent assay and immunoprecipitation have been developed.
      This review article describes the immunopathological features of autoimmune
      bullous diseases and the immunological and molecular tests used for their
      diagnosis and monitoring.

PMID- 17521375
TI  - Time course and mechanisms of mental stress-induced changes and their recovery:
      hematocrit, colloid osmotic pressure, whole blood viscosity, coagulation times,
      and hemodynamic activity.
AB  - The mechanisms for stress-induced changes in hematocrit and blood viscosity are
      unclear. Twenty-two males completed experimental (30 min baseline, 10 min mental
      stress, 30 min recovery) and no-stress control conditions (70 min). Hemostatic
      and hemodynamic activity were measured throughout. Hematocrit, colloid osmotic
      pressure, and blood viscosity displayed parallel patterns: a progressive increase
      with stress, followed by a gradual recovery. Correlational and covariance
      analyses indicated that the increase in hematocrit may be mediated by arterial
      pressure whereas recovery may be mediated by colloid osmotic pressure. Analyses
      also indicated that acute changes in blood viscosity may depend on hematocrit.
      These data suggest that stress disturbs hematocrit, colloid osmotic pressure, and
      blood viscosity through arterial pressure. Poststress, elevated colloid osmotic
      pressure may drive its own recovery and that of hematocrit and blood viscosity.

PMID- 17521376
TI  - Sequential processing of interaural timing differences for sound source
      segregation and spatial localization: evidence from event-related cortical
      potentials.
AB  - Cortical processing of interaural timing differences (ITDs) was investigated with
      event-related potential (ERP) measurements in 16 human participants who were
      required in separate tasks to detect or to spatially localize dichotically
      embedded pitches. ITDs elicited three ERP components labeled ORN, N2, and P400.
      The ORN occurred at a latency of 150-250 ms and was elicited by ITDs regardless
      of location or task. In contrast, the N2 response (250-350 ms) was strongly
      modulated by location and showed larger amplitudes for the localization task than
      for the detection task. Finally, ITDs in the detection task elicited a P400 at a
      latency of 400-500 ms, but this response was entirely absent from ERPs elicited
      by identical stimuli in the localization task. These results are consistent with
      a sequential model of auditory perception in which segregation of concurrent
      sounds is followed by domain-specific processing of object location and identity.

PMID- 17521378
TI  - Backward masking and visual mismatch negativity: electrophysiological evidence
      for memory-based detection of deviant stimuli.
AB  - Sequences composed of two different colored checkerboard patterns (standard and
      deviant) were presented to adults. Each pattern was followed by a mask with
      stimulus onset asynchronies (SOAs) varying between 14 and 174 ms. ERPs were
      recorded to the deviant and standard stimuli while the participants detected
      changes of a cross, which was continuously present at the center of the screen.
      In further experiments, the participants performed a Go-NoGo task detecting the
      deviant checkerboards. Deviant stimuli elicited an occipital negative component
      with 124-132 ms mean latency (the visual mismatch negativity, vMMN) at test
      (standard or deviant)-to-mask SOAs longer than 27 ms. No vMMN amplitude increase
      was observed beyond 40 ms test-to-mask intervals, whereas detection of deviant
      checkerboard patterns improved up to 174-ms SOA. Therefore the processes
      underlying vMMN elicitation cannot fully explain the overt detection of visual
      deviance.

PMID- 17521377
TI  - Thinking ahead: the role and roots of prediction in language comprehension.
AB  - Reviewed are studies using event-related potentials to examine when and how
      sentence context information is used during language comprehension. Results
      suggest that, when it can, the brain uses context to predict features of likely
      upcoming items. However, although prediction seems important for comprehension,
      it also appears susceptible to age-related deterioration and can be associated
      with processing costs. The brain may address this trade-off by employing multiple
      processing strategies, distributed across the two cerebral hemispheres. In
      particular, left hemisphere language processing seems to be oriented toward
      prediction and the use of top-down cues, whereas right hemisphere comprehension
      is more bottom-up, biased toward the veridical maintenance of information. Such
      asymmetries may arise, in turn, because language comprehension mechanisms are
      integrated with language production mechanisms only in the left hemisphere (the
      PARLO framework).

PMID- 17521379
TI  - Effects of cigarette smoking on prepulse inhibition, its attentional modulation,
      and vigilance performance.
AB  - Startle eyeblink modification was measured during a degraded stimulus continuous
      performance test following both smoking and overnight abstinence among student
      smokers to measure the effects of smoking on both early and late attentional
      processes. A group of nonsmokers was tested twice without nicotine manipulation.
      A startling noise was presented either 240 or 1200 ms following target and
      nontarget stimuli presented during the task. Startle inhibition at 240 ms was
      greater following targets than nontargets following smoking and during both
      nonsmoker tests, but this attentional modulation was absent following abstinence.
      At the 1200-ms probe position, target and nontarget stimuli produced
      nondifferential inhibition during both tests for both groups. Abstinence among
      smokers produced reliably lower vigilance performance compared to ad lib smoking.
      The results indicate that smoking abstinence affects the early stages of stimulus
      processing.

PMID- 17521380
TI  - Multiple motifs regulate trafficking of the LAMP-like protein p67 in the ancient
      eukaryote Trypanosoma brucei.
AB  - p67 is a lysosome-associated membrane protein-like lysosomal type I transmembrane
      glycoprotein in African trypanosomes. The p67 cytoplasmic domain (CD) is both
      necessary and sufficient for lysosomal targeting in procyclic insect-stage
      parasites. The p67CD contains two [DE]XXXL[LI]-type dileucine motifs, which
      function as lysosomal targeting signals in mammalian cells. Using a green
      fluorescent protein fusion to the p67 transmembrane and cytoplasmic domains as a
      reporter system, we investigated the role of these motifs in lysosomal targeting
      in procyclic trypanosomes. Pulse-chase turnover studies, steady-state
      immunolocalization and quantitative flow cytometry all gave consistent results.
      Mutagenesis of the membrane-distal dileucine motif impairs lysosomal trafficking
      leading to partial appearance of the reporter on the cell surface. Mutagenesis of
      the membrane-proximal motif has little effect on proper targeting. Simultaneous
      mutagenesis of both motifs results in quantitative delivery to the cell surface.
      Thus, the distal motif plays a dominant role, but both dileucine motifs are
      necessary for maximal lysosomal targeting. Additional studies suggest that the
      upstream acidic residues in each motif influence lysosomal targeting and may also
      affect forward trafficking in the early secretory pathway. These results strongly
      suggest an evolutionary conservation in lysosomal trafficking mechanisms in the
      ancient eukaryote Trypanosoma brucei.

PMID- 17521381
TI  - Activated somatostatin type 2 receptors traffic in vivo in central neurons from
      dendrites to the trans Golgi before recycling.
AB  - Understanding the trafficking of G-protein-coupled receptors (GPCRs) is of
      particular importance, especially when modifications of the neurochemic
      environment occur as in pathological or therapeutic circumstances. In the central
      nervous system, although some GPCRs were reported to internalize in vivo, little
      is known about their trafficking downstream of the endocytic event. To address
      this issue, distribution and expression pattern of the major somatostatin
      receptor subtype, the somatostatin type 2 (sst2), was monitored in the
      hippocampus using immunofluorescence, autoradiographic and immunogold experiments
      from 10 minutes to 7 days after in vivo injection of the receptor agonist
      octreotide. We then analyzed whether postendocytic trafficking of the receptor
      was dependent upon integrity of the microtubule network using colchicine-injected
      animals. Together, our results suggest that upon agonist stimulation, dendritic
      receptors are retrogradely transported through a microtubule-dependent mechanism
      to a trans Golgi domain enriched in the t-SNARE syntaxin 6 and trans Golgi
      network 38 proteins, before recycling. Because we show that the exit rate from
      the trans Golgi apparatus back to the plasma membrane (hours) is slower than the
      entry rate (minutes), the neuronal postendocytic trafficking of sst2 receptor is
      likely to have functional consequences in several neurological diseases in which
      an increase in somatostatin release occurs.

PMID- 17521382
TI  - Risk factors for the development of coronary artery disease of a grafted heart as
      detected very early after orthotopic heart transplantation.
AB  - Orthotopic heart transplantation (OHTx) represents a well established method of
      end-stage heart failure treatment. Allograft coronary artery disease (CAD) still
      remains to be one of the most important limiting factors for OHTx recipients'
      long-term survival. Unfortunately, allograft CAD can be detected very early after
      OHTx. Our study was designed to identify risk factors for early allograft CAD
      development. Eighty-three OHTx recipients (18 females, 65 males, mean age 50.55
      +/- 11.04 years) with coronary intravascular ultrasound examination performed
      early after OHTx (29.81 +/- 12.45 days) formed the study population. The impact
      of a number of pre-, peri- and early post-transplant possible risk factors on
      early allograft CAD development was studied. By multivariate analysis, only
      higher donor age (P < 0.001) and higher recipient's body mass index (P = 0.003)
      were found to represent risk factors for the early development of allograft CAD.

PMID- 17521383
TI  - Evaluating the accuracy of functional biomarkers for detecting histological
      changes in chronic allograft nephropathy.
AB  - The most common cause of late kidney transplant failure is chronic allograft
      nephropathy (CAN). Much research has focused on identifying biomarkers (or
      correlates) that would predict subsequent CAN and allow timely intervention.
      Functional biomarkers such as serum creatinine and estimated glomerular
      filtration rate (eGFR) have been widely adopted, even though they have not been
      rigorously evaluated as surrogate markers. This study evaluated serum creatinine
      and eGFR for predicting the early histopathological changes seen in transplant
      protocol biopsies (TPB). We prospectively followed 289 kidney transplant patients
      in the Southern Alberta Transplant Program who had TPB at 6-12 months post
      transplant. Tissue samples (n = 280) were independently examined by renal
      pathologists. The ability of serum creatinine or eGFR to predict the threshold
      level for abnormal histopathology was evaluated by calculating the area under the
      receiver operator characteristic curve. Serum creatinine and eGFR had poor
      predictive value (most confidence intervals included 0.5, indicating no
      predictive ability) for ten individual histological measurements (Banff 97
      scores), and the Chronic Allograft Damage Index. We conclude that serum
      creatinine and eGFR have a limited clinical role in predicting the early
      histopathological changes that precede CAN and should not be used for this
      purpose.

PMID- 17521384
TI  - ABO-incompatible liver transplantation for critically ill adult patients.
AB  - ABO incompatible (ABO-In) liver transplant remains a controversial solution to
      acute liver failure in adults. Adult liver recipients with acute liver failure or
      severely decompensated end-stage disease, intubated and/or in the intensive care
      unit, were grouped as ABO-In (n = 14), ABO-compatible (n = 29, ABO-C) and ABO
      identical (n = 65, ABO-Id). ABO-In received quadruple immunosuppression with
      antibody-depleting induction agents (except two), calcineurin inhibitors,
      antimetabolites and steroids. No significant difference of patient and graft
      survivals was observed among ABO-In, ABO-C and ABO-Id: graft survivals were 64%,
      62% and 67%, respectively, in 1 year and 56%, 54% and 60%, respectively, in 5
      years; patient survivals 86%, 69% and 67%, respectively, in 1 year and 77%, 61%
      and 62%, respectively, in 5 years. Three ABO-In grafts were lost (one hyper-acute
      rejection and two hepatic artery thrombosis). Surgical and infectious
      complications were similarly distributed between groups, except the hepatic
      artery thrombosis, more frequent in ABO-In (2, 14%) than ABO-I (1, 1.5%, P <
      0.05). In contrast to previous studies, no significant difference of patient and
      graft survivals could be observed among all ABO-compatibility settings. Our
      results suggest that ABO-incompatible transplants should be viewed as an
      important therapeutic option in adult patients with acute liver failure awaiting
      an emergency procedure.

PMID- 17521385
TI  - Late onset arterial conduit aneurysm in a liver transplant patient.

PMID- 17521386
TI  - Longevity determined by developmental arrest genes in Caenorhabditis elegans.
AB  - The antagonistic pleiotropy theory of aging proposes that aging takes place
      because natural selection favors genes that confer benefit early on life at the
      cost of deterioration later in life. This theory predicts that genes that impact
      development would play a key role in shaping adult lifespan. To better understand
      the link between development and adult lifespan, we examined the genes previously
      known to be essential for development. From a pool of 57 genes that cause
      developmental arrest after inhibition using RNA interference, we have identified
      24 genes that extend lifespan in Caenorhabditis elegans when inactivated during
      adulthood. Many of these genes are involved in regulation of mRNA translation and
      mitochondrial functions. Genetic epistasis experiments indicate that the
      mechanisms of lifespan extension by inactivating the identified genes may be
      different from those of the insulin/insulin-like growth factor 1 (IGF-1) and
      dietary restriction pathways. Inhibition of many of these genes also results in
      increased stress resistance and decreased fecundity, suggesting that they may
      mediate the trade-offs between somatic maintenance and reproduction. We have
      isolated novel lifespan-extension genes, which may help understand the intrinsic
      link between organism development and adult lifespan.

PMID- 17521387
TI  - SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric
      restriction.
AB  - The sirtuin family of nicotinamide adenine dinucleotide-dependent (NAD)
      deacetylases plays an important role in aging and metabolic regulation. In yeast,
      the Sir2 gene and its homolog Hst2 independently mediate the action of caloric
      restriction on lifespan extension. The mammalian Sir2 ortholog, SIRT1, is up
      regulated by caloric restriction and deacetylates a variety of substrates,
      including histones and the forkhead box O (FOXO) transcription factors. The
      mammalian ortholog of Hst2, SIRT2, was shown to co-localize with microtubules and
      functions as alpha-tubulin deacetylase. During G2/M phase, SIRT2 proteins enter
      nuclei and deacetylate histones. We report here that the expression of SIRT2 is
      elevated in the white adipose tissue and kidney of caloric-restricted mice.
      Oxidative stress, such as hydrogen peroxide treatment, also increases SIRT2
      expression in cells. We have demonstrated that SIRT2 binds to FOXO3a and reduces
      its acetylation level. SIRT2 hence increases FOXO DNA binding and elevates the
      expression of FOXO target genes, p27(Kip1), manganese superoxide dismutase and
      Bim. As a consequence, SIRT2 decreases cellular levels of reactive oxygen
      species. Furthermore, as Bim is a pro-apoptotic factor, SIRT2 promotes cell death
      when cells are under severe stress. Therefore, mammalian SIRT2 responds to
      caloric restriction and oxidative stress to deacetylate FOXO transcription
      factors.

PMID- 17521388
TI  - Werner syndrome protein prevents DNA breaks upon chromatin structure alteration.
AB  - Werner syndrome is a rare disorder characterized by genome instability and the
      premature onset of several pathologies associated with aging. The gene
      responsible for Werner syndrome codes for a RecQ-type DNA helicase and is
      believed to be involved in different aspects of DNA repair, replication, and
      transcription. The human Werner protein (WRN) translocates from nucleoli to the
      nucleoplasm upon DNA damage. Here, for the first time we show WRN translocation
      following treatment with chloroquine (CHL) or trichostatin A (TSA), agents that
      alter chromatin structure without producing DNA breaks. In contrast to normal
      cells, WRN deficient human and murine cells incurred extensive DNA breaks upon
      CHL or TSA treatment, indicating a functional role for WRN in the proper response
      to these agents. Cells deficient for another RecQ-type helicase, Bloom syndrome,
      were not sensitive to these agents. WRN is known from in vitro studies to bind
      and stimulate the activity of topoisomerase I (Topol). CHL enhanced the
      association between WRN and Topol, suggesting that topological stress elicits a
      requirement for the stimulation of Topol by WRN. Supporting this idea,
      overexpression of Topol reduced CHL and TSA-induced DNA breaks in WRN null cells.
      We thus describe a novel function for WRN in ensuring genome stability to act in
      concert with Topol to prevent DNA breaks, following alterations in chromatin
      topology.

PMID- 17521389
TI  - Alterations in xenobiotic metabolism in the long-lived Little mice.
AB  - Our previous microarray expression analysis of the long-lived Little mice
      (Ghrhr(lit/lit)) showed a concerted up-regulation of xenobiotic detoxification
      genes. Here, we show that this up-regulation is associated with a potent increase
      in resistance against the adverse effects of a variety of xenobiotics, including
      the hepatotoxins acetaminophen and bromobenzene and the paralyzing agent
      zoxazolamine. The classic xenobiotic receptors Car (Constitutive Androstane
      Receptor) and Pxr (Pregnane X Receptor) are considered key regulators of
      xenobiotic metabolism. Using double and triple knockout/mutant mouse models we
      found, however, that Car and Pxr are not required for the up-regulation of
      xenobiotic genes in Little mice. Our results suggest instead that bile acids and
      the primary bile acid receptor Fxr (farnesoid X receptor) are likely mediators of
      the up-regulation of xenobiotic detoxification genes in Little mice. Bile acid
      levels are considerably elevated in the bile, serum, and liver of Little mice. We
      found that treatment of wild-type animals with cholic acid, one of the major bile
      acids elevated in Little mice, mimics in large part the up-regulation of
      xenobiotic detoxification genes observed in Little mice. Additionally, the loss
      of Fxr had a major effect on the expression of the xenobiotic detoxification
      genes up-regulated in Little mice. A large fraction of these genes lost or
      decreased their high expression levels in double mutant mice for Fxr and Ghrhr.
      The alterations in xenobiotic metabolism in Little mice constitute a form of
      increased stress resistance and may contribute to the extended longevity of these
      mice.

PMID- 17521390
TI  - IL-12/23p40-dependent clearance of Anaplasma phagocytophilum in the murine model
      of human anaplasmosis.
AB  - Human anaplasmosis is an emerging infectious disease transmitted by ticks that
      can be potentially fatal in the immunocompromised and the elderly. The mechanisms
      of defense against the causative agent, Anaplasma phagocytophilum, are not
      completely understood; however, interferon (IFN)-gamma plays an important role in
      pathogen clearance. Here, we show that IFN-gamma is regulated through an early IL
      12/23p40-dependent mechanism. Interleukin (IL)-12/23p40 is regulated in
      macrophages and dendritic cells after activation by microbial agonists and
      cytokines and constitutes a subunit of IL-12 and IL-23. IL-12/23p40-deficient
      mice displayed an increased A. phagocytophilum burden, accelerated
      thrombocytopenia and increased neutrophil numbers in the spleen at day 6
      postinfection. Infection of MyD88- and mitogen-activated kinase kinase 3 (MKK3)
      deficient mice suggested that the early susceptibility due to IL-12/23p40
      deficiency was not dependent on signaling through MyD88 or MKK3. The lack of IL
      12/23p40 reduced IFN-gamma production in both CD4(+) and CD8(+) T cells although
      the effect was more pronounced in CD4(+) T cells. Our data suggest that the
      immune response against A. phagocytophilum is a multifactorial and cooperative
      process. The IL-12/23p40 subunit drives the CD4(+) Th1 immune response in the
      early phase of infection and IL-12/23p40-independent mechanisms ultimately
      contribute to pathogen elimination from the host.

PMID- 17521391
TI  - Helicobacter pylori flagella: antigenic profile and protective immunity.
AB  - Reproducible induction of sterilizing immunity, essential for an effective
      Helicobacter pylori vaccine, remains elusive. As motility is essential for
      gastric colonization by Helicobacter, we evaluated whether a vaccine targeting
      flagella induces improved protection. Mice immunized with a vaccine enriched for
      H. pylori flagella sheath proteins exhibited significantly reduced colonization,
      equivalent to that observed in mice immunized with whole-cell lysate. Two
      dimensional profiles indicated that flagella contain proteins not evident in
      whole-cell lysate. Moreover, comparison of Western blot profiles using whole-cell
      lysate antisera revealed striking differences in antigenicity.

PMID- 17521392
TI  - Gastric inflammatory markers and interleukins in patients with functional
      dyspepsia treated with astaxanthin.
AB  - The chronic active inflammation caused by Helicobacter pylori is dominated by
      neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins are
      involved in the inflammatory process. The aim of this study was to investigate
      the effect of astaxanthin on gastric inflammation in patients with functional
      dyspepsia. Forty-four consecutive patients were included, and biopsies were
      examined for IL-4, IL-6, IL-8, IL-10, interferon-gamma, CD4, CD8, CD14, CD19,
      CD25 and CD30. Patients were randomized: 21 patients were treated with 40 mg of
      astaxanthin daily, and 23 patients were treated with a placebo. There was a
      significant decrease in gastric inflammation in H. pylori-positive patients from
      both groups. There were no significant changes in the density of H. pylori or in
      any of the interleukins during or after treatment. There was a significant up
      regulation of CD4 and down-regulation of CD8 in patients with H. pylori treated
      with astaxanthin. Astaxanthin had an effect on the inflammation and on the
      density of H. pylori in mice in a study where the diet could be standardized
      without antioxidants (Bennedsen et al., 1999). These dietary conditions are
      impossible in studies involving humans, and may be due to the minor effect when
      the host have access to antioxidants in their diet.

PMID- 17521393
TI  - Mycobacterium tuberculosis H37Rv induces monocytic release of interleukin-6 via
      activation of mitogen-activated protein kinases: inhibition by N-acetyl-L
      cysteine.
AB  - The release of proinflammatory cytokines after mycobacterial infection is a host
      immune response that may be propitious or deleterious to the host. Elevated
      levels of interleukin (IL)-6 are present in plasma of patients with active
      tuberculosis infection. The aim of this study was to investigate the role of
      mitogen-activated protein kinases in the secretion of interleukin-6 in THP-1
      cells and human primary monocytes that were infected with Mycobacterium
      tuberculosis H37Rv, and its regulation by N-acetyl-L-cysteine, a potential
      antimycobacterial agent. Exposure of THP-1 human monocytes to M. tuberculosis
      H37Rv induced rapidly, in a time-dependent manner, the phosphorylation of mitogen
      activated protein kinase kinase 3/6 and p38 mitogen-activated protein kinase,
      accompanied by an upregulation of interleukin-6. Using highly specific inhibitors
      of mitogen-activated protein kinase kinase-1, p38 mitogen-activated protein
      kinase and nuclear factor-kappaB, we found that extracellular-signal regulated
      kinase 1/2, p38 mitogen-activated protein kinase and nuclear factor-kappaB were
      essential for M. tuberculosis H37Rv-induced interleukin-6 production in human
      primary monocytes. Pretreatment with N-acetyl-L-cysteine reduced, in a dose
      dependent manner, M. tuberculosis H37Rv-induced activation of mitogen-activated
      protein kinase kinase 3/6 and interleukin-6 production in THP-1 cells.

PMID- 17521394
TI  - Comparative evaluation of therapeutic DNA vaccines against Trypanosoma cruzi in
      mice.
AB  - Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major
      public health problem in most of Latin America. A key priority is the development
      of new treatments, due to the poor efficacy of current ones. We report here the
      comparative evaluation of therapeutic DNA vaccines encoding various T. cruzi
      antigens. ICR mice infected with 500 parasites intraperitoneally were treated at
      5 and 12 days postinfection with 20 microg of plasmid DNA encoding T. cruzi
      antigens TSA-1, TS, ASP-2-like, Tc52 or Tc24. Treatment with plasmid encoding TS
      and/or ASP-2-like antigens had no significant effect on parasitemia or survival.
      Treatment with Tc52 DNA significantly reduced parasitemia, as well as cardiac
      parasite burden, and improved survival, although myocarditis was not
      significantly affected. Finally, treatment with plasmids encoding Tc24 and TSA-1
      induced the most complete control of disease as evidenced by significant
      reductions in parasitemia, mortality, myocarditis and heart parasite burden.
      These data demonstrate that therapeutic vaccine efficacy is dependent on the
      antigen and suggest that DNA vaccines encoding Tc24, TSA-1, and Tc52 represent
      the best candidates for further studies of a therapeutic vaccine against Chagas
      disease.

PMID- 17521395
TI  - Production of recombinant gG-1 protein of herpes simplex virus type 1 in a
      prokaryotic system in order to develop a type-specific enzyme-linked
      immunosorbent assay kit.
AB  - The herpes simplex viruses are important causes of disease worldwide. Herpes
      simplex virus type 1 (HSV-1) is the primary cause of oral-facial and pharyngeal
      infections and may cause herpetic whitlow, eye infections as well as severe and
      sometimes dangerous infections of the eyes and brain. HSV-1 also accounts for 10
      15% of all genital herpetic infections. Therefore, laboratory diagnosis of this
      virus and development of diagnostic serological techniques for HSV-1 is of
      particular importance. In the present study, pTrc His2A-gG1 plasmid, containing
      the full-length glycoprotein G (gG) protein, was produced in a prokaryotic system
      for the first time. Upon confirmation of a 37-kDa gG-1 protein production in a
      prokaryotic system based on western blotting and monoclonal antibodies, the
      protein was produced at a large scale and purified by ion-exchange chromatography
      using DEAE-sepharose. An HSV-1 type-specific diagnostic kit was designed and
      developed and the specificity and sensitivity of this kit were demonstrated to be
      89.5% and 100%, respectively, as compared with a commercially available kit. A
      significant correlation was shown between the developed kit and the commercial
      kit.

PMID- 17521396
TI  - The clinical outcome of small (<20 mm) arterially enhancing nodules on MRI in the
      cirrhotic liver.
AB  - OBJECTIVES: To evaluate the outcome of arterially enhancing nodules (AENs)
      measuring <20 mm detected on MRI in patients with cirrhosis. METHODS: Prospective
      analysis of 54 patients with a total of 161 AENs <20 mm on MRI. Inclusion
      criteria included a minimum of 12 months of MRI follow-up or histological
      evaluation of the AEN. Key exclusions were patients with an AEN >20 mm or prior
      diagnosis of HCC. Two radiologists blinded to the clinical and pathological data
      reviewed serial MRIs and classified the AENs as no longer visible, stable,
      increasing, or decreasing in size. RESULTS: A total of 161 AENs were identified
      and were followed by serial MRI for a mean of 24 months. Eighty (50%) AENs were
      no longer visible on repeat imaging, 42 (26%) remained stable, 1 of which was
      diagnosed as HCC on short-term follow-up, 8 (5%) increased in size and were
      subsequently diagnosed as HCC, and 24 (15%) decreased in size. In addition, 7
      AENs (4%) were diagnosed on biopsy immediately following the initial MRI. Overall
      MR characteristics diagnostic of HCC were growth > or =2 mm and peripheral rim
      enhancement on initial MRI. CONCLUSIONS: The majority (90%) of AENs <20 mm in
      cirrhosis are benign. The presence of rim enhancement or interval growth of an
      AEN are suggestive of HCC.

PMID- 17521397
TI  - Effect of tegaserod on recto-sigmoid tonic and phasic activity in constipation
      predominant irritable bowel syndrome.
AB  - OBJECTIVES: In irritable bowel syndrome (IBS), the modulation of neural pathways
      may be altered and we have recently shown that postprandial recto-sigmoid tone
      modification is impaired. On pathophysiological grounds, we do not know whether
      this alteration may have a role in symptom onset and, in particular, whether an
      effective drug, such as tegaserod, can improve this response together with
      symptom severity. METHODS: Twenty-two female patients with constipation
      predominant IBS (IBS-C), diagnosed according to Rome II criteria, were studied.
      All subjects underwent an evaluation of the presence and severity of IBS symptoms
      and the recto-sigmoid barostat test to measure fasting and postprandial recto
      sigmoid tone and phasic contractility. They were then randomly assigned to
      receive either tegaserod 6 mg b.i.d (12 patients) or placebo tablets (10
      patients) for 4 wk, according to a double-blind protocol. Symptom assessment and
      recto-sigmoid tone and contractility were re-evaluated at the end of the
      treatment. RESULTS: Both symptom severity and postprandial modification of recto
      sigmoid tone improved only in the tegaserod group and a significant correlation
      was evident between the improvement of bloating and the improvement of
      postprandial recto-sigmoid tone modification. No effect of tegaserod on recto
      sigmoid motility index or correlation between motility index and symptom
      improvement was evident. CONCLUSIONS: In IBS-C female patients, the
      administration of tegaserod improves symptom severity and is accompanied by an
      improvement of recto-sigmoid tone response to a meal.

PMID- 17521398
TI  - The association between Helicobacter pylori infection and early gastric cancer: a
      meta-analysis.
AB  - OBJECTIVE: Helicobacter pylori (H. pylori) is recognized as a definite carcinogen
      for gastric cancer. The prevalence of H. pylori infection in patients with
      gastric cancer varies widely among studies and no meta-analysis on the prevalence
      of H. pylori infection in early gastric cancer (EGC) has been performed. We aimed
      to review systematically the relationship between H. pylori infection and EGC,
      and different types of EGC. METHODS: Observational studies reporting raw data on
      the prevalence of H. pylori infection in EGC and controls, or comparing different
      types of EGC, conducted in adult populations, and published in the English
      language were identified through MEDLINE and EMBASE up to June 2006. RESULTS: Of
      87 relevant studies, 19 case-control studies met inclusion criteria. Of these, 15
      studies compared EGC (N = 2,722) and non-neoplasm controls (N = 13,976) or
      advanced gastric cancer (AGC) (N = 1,130), 9 studies compared the intestinal-type
      (I-EGC) and diffuse-type (D-EGC) of EGC, and 2 studies compared the
      differentiated-type (DF-EGC) and undifferentiated-type (UDF-EGC) of EGC and were
      included in the meta-analysis. The prevalence of H. pylori infection was
      significantly higher in patients with EGC (87.3%) than in non-neoplasm controls
      (61.4%) (OR 3.38, 95% CI 2.15-5.33, P < 0.00001). However, significant
      heterogeneity was seen (P < 0.00001). Four large sample (N > or = 100) studies (N
      = 2,060) may result in the heterogeneity, but the conclusion remained unchanged
      when sensitivity analysis was made with the other 11 homogeneous small sample
      studies alone, in which the prevalence of H. pylori infection was significantly
      higher in EGC (N = 662) than that in controls (N = 5,898) (87.8%vs 68.6%, P <
      0.00001), and the odds ratio (OR 3.28, 95% CI 2.34-4.61) was similar to the large
      sample studies alone (OR 3.40, 95% CI 1.14-10.12). The prevalence of H. pylori
      infection in EGC was significantly higher than in AGC (6 studies) (OR 2.13, 95%
      CI 1.75-2.59) and 16-fold higher in patients with DF-EGC than in those with UDF
      EGC (OR 16.53, 95% CI 2.64-103.43). No significant difference in the prevalence
      of H. pylori infection was seen between the patients with I-EGC and D-EGC types
      (OR 0.75, 95% CI 0.26-2.18). CONCLUSIONS: This study indicates that H. pylori
      infection is strongly associated with early gastric cancer when compared with non
      neoplasm controls or advanced gastric cancer. To determine more accurately the
      effect size of H. pylori in EGC, age-matched normal controls or adjusting for age
      in the analysis should be considered in H. pylori-related gastric cancer case
      control studies.

PMID- 17521399
TI  - Diet resistant celiac disease.

PMID- 17521400
TI  - Comparison of endoscopic ultrasonography and magnetic resonance
      cholangiopancreatography in the diagnosis of pancreatobiliary diseases: a
      prospective study.
AB  - OBJECTIVES: To compare the diagnostic value of endoscopic ultrasonography (EUS)
      and magnetic resonance cholangiopancreatography (MRCP) in: (a) patients with a
      dilated biliary tree unexplained by ultrasonography (US) (group 1), and (b) the
      diagnosis of choledocholithiasis in patients with nondilated biliary tree (group
      2). METHODS: Patients were prospectively evaluated with EUS and MRCP. The gold
      standard used was surgery or EUS-FNA and ERCP, intraoperative cholangiography, or
      follow-up when EUS and/or MRCP disclosed or precluded malignancy, respectively.
      Likelihood ratios (LR) and pretest and post-test probabilities for the diagnosis
      of malignancy and choledocholithiasis were calculated. RESULTS: A total of 159
      patients met one of the inclusion criteria but 24 of them were excluded for
      different reasons. Thus, 135 patients constitute the study population. The most
      frequent diagnosis was choledocholithiasis (49% in group 1 and 42% in group 2, P=
      0.380) and malignancy was more frequent in group 1 (35%vs 7%, respectively, P <
      0.001). When EUS and MRCP diagnosed malignancy, its prevalence in our series
      (35%) increased up to 98% and 96%, respectively, whereas it decreased to 0% and
      2.6% when EUS and MRCP precluded this diagnosis. In patients in group 2, when EUS
      and MRCP made a positive diagnosis of choledocholithiasis, its prevalence (42%)
      increased up to 78% and 92%, respectively, whereas it decreased to 6% and 9% when
      any pathologic finding was ruled out. CONCLUSIONS: EUS and MRCP are extremely
      useful in diagnosing or excluding malignancy and choledocholithiasis in patients
      with dilated and nondilated biliary tree. Therefore, they are critical in the
      approach to the management of these patients.

PMID- 17521401
TI  - Lack of colonic neoplastic lesions in patients under 50 yr of age with
      hematochezia: a multicenter prospective study.
AB  - OBJECTIVES: It is still not clear what is the best way of evaluating rectal
      bleeding in young people. Our aim was to examine the prevalence of neoplastic
      colonic lesions in these patients. METHODS: This prospective, multicenter study
      enrolled 622 patients aged 30-50 yr (F 232/M 390) consecutively seen in 14 open
      access endoscopy departments for hematochezia, defined as bright red blood from
      the rectum, red blood noted either in the feces, on toilet paper, or in the
      toilet bowl. At colonoscopy, pathology was stratified as either proximal or
      distal to the splenic flexure. Exclusion criteria were a history of colitis,
      colorectal cancer, polyps, anemia, significant weight loss, severe bleeding, or
      strong family history of colorectal cancer. RESULTS: Malignant polyps were found
      in two patients (0.6%), aged 30-40 yr, one in the rectum and one in the sigmoid.
      A malignant polyp of the cecum was found in a 41-yr-old patient. Another, aged
      47, had a malignant granular-cell tumor of the rectum. A total of 35 advanced
      adenomas were identified in 18 patients. In 7 patients (2.2 %) within the 30-40
      yr age bracket we found 8 advanced adenomas (all in the rectum/sigmoid). The
      other 27 advanced adenomas were in 11 patients (3.5%) in the 41-50 yr age
      bracket. In this age group we observed 3 patients with 10 isolated proximal
      advanced adenomas. CONCLUSIONS: In patients younger than 40 yr with hematochezia,
      advanced neoplastic lesions are rare and usually located in the rectum and
      sigmoid colon. Sigmoidoscopy appears to be sufficient for evaluation in these
      patients.

PMID- 17521403
TI  - Biodegradation of phytane (2,6,10,14-tetramethylhexadecane) and accumulation of
      related isoprenoid wax esters by Mycobacterium ratisbonense strain SD4 under
      nitrogen-starved conditions.
AB  - The accumulation of storage lipids during the biodegradation of 2,6,10,14
      tetramethylhexadecane (phytane) by Mycobacterium ratisbonense strain SD4 grown
      under nitrogen-starved conditions was investigated. Detailed chemical analysis of
      intracellular metabolites revealed the existence of (at least) three different
      pathways for the catabolism of phytane, and the accumulation of significant
      proportions (39% of the total lipids) of several isoprenoid wax esters formed by
      condensation of oxidation products of the hydrocarbon. In contrast,
      triacylglycerols but no wax esters were accumulated by strain SD4 grown on
      hexadecane, the unbranched homologue of phytane.

PMID- 17521404
TI  - Factors involved in the germination and inactivation of Bacillus anthracis spores
      in murine primary macrophages.
AB  - Since macrophages have been implicated in inhalation anthrax either for defense
      and/or as enablers for spore trafficking, their function has been further
      defined. Spores were efficiently taken up by primary mouse bone marrow-derived
      macrophages even in the absence of serum but a minimal amount was required for
      spore germination and subsequent inactivation. With 10% fetal bovine serum (FBS)
      virtually all of the spores germinated but when the concentration of FBS was
      lowered to 1.0% or less, or when 10% horse serum replaced FBS, only 50% of the
      spores were inactivated within 1 h with no subsequent loss. Chloramphenicol,
      which blocks spore outgrowth but not germination, did not inhibit spore killing
      in macrophages. Based on complete inhibition of germination by d-alanine plus d
      histidine, it is likely that only two of the several Bacillus anthracis
      germination systems are involved within macrophages. d-Histidine inhibits the
      gerH system previously implicated in germination within macrophages. d-Alanine is
      likely to block the gerX system since disruption of the gerXA gene resulted in
      little germination within 4 h in macrophages. Macrophages provide a major line of
      defense against infection by efficiently sequestering spores and in the presence
      of minimal nutrients effectively killing those that germinate before outgrowth.

PMID- 17521405
TI  - Detection of deoxynivalenol based on a single-chain fragment variable of the
      antideoxynivalenol antibody.
AB  - Immunological detection of low molecular weight toxins, such as deoxynivalenol
      using single-chain antibody fragment (scFv), is a potentially novel and safe
      method of diagnosing fungal infection and food contamination. To develop a
      deoxynivalenol detection procedure based on scFv, deoxynivalenol was first
      conjugated to horseradish peroxidase (HRP) for immunoassay. Deoxynivalenol was
      initially activated using N-[p-maleimidophenyl] isocyanate and subsequently
      conjugated to S-acetyl thioglycolic acid N-hydroxysuccinimide-activated HRP.
      Sodium dodecylsulphate polyacrylamide gel electrophoresis and enzyme-linked
      immunosorbent assay (ELISA) analysis confirmed covalent attachment of
      deoxynivalenol to HRP successfully. Competitive direct-ELISA based on
      antideoxynivalenol scFv was used to detect deoxynivalenol in spiked and natural
      contaminated wheat samples, and the results showed that scFv is applicable in
      deoxynivalenol detection of contaminated wheat samples. This work confirms that
      sensitive and specific scFv against fungal toxins can be applicable in diagnosis
      of fungal infection.

PMID- 17521406
TI  - Improved purification and PCR amplification of DNA from environmental samples.
AB  - Purification and PCR amplification procedures for DNA extracted from
      environmental samples (soil, compost, and river sediment) were improved by
      introducing three modifications: precipitation of DNA with 5% polyethylene glycol
      8000 (PEG) and 0.6 M NaCl; filtration with a Sepharose 4B
      polyvinylpolypyrrolidone (PVPP) spin column; and addition of skim milk (0.3% w/v)
      to the PCR reaction solution. Humic substances' concentration after precipitation
      with 5% PEG was 2.57-, 5.3-, and 78.9-fold lower than precipitation with 7.5%
      PEG, 10% PEG, and isopropanol, respectively. After PEG precipitation, Sepharose,
      PVPP and the combined (Sepharose-PVPP) column removed 92.3%, 89.5%, and 98%,
      respectively, of the remaining humic materials. Each of the above-mentioned
      modifications improved PCR amplification of the 16S rRNA gene. DNA extracted by
      the proposed protocol is cleaner than DNA extracted by a commercial kit.
      Nevertheless, the improvement of DNA purification did not improve the detection
      limit of atrazine degradation gene atzA.

PMID- 17521407
TI  - Regulation of arbuscular mycorrhization by apoplastic invertases: enhanced
      invertase activity in the leaf apoplast affects the symbiotic interaction.
AB  - The effect of constitutive invertase overexpression on the arbuscular mycorrhiza
      (AM) is shown. The analysis of the enhanced potential for sucrose cleavage was
      performed with a heterozygous line of Nicotiana tabacum 35S::cwINV expressing a
      chimeric gene encoding apoplast-located yeast-derived invertase with the CaMV35S
      promoter. Despite the 35S promoter, roots of the transgenic plants showed no or
      only minor effects on invertase activity whereas the activity in leaves was
      increased at different levels. Plants with strongly elevated leaf invertase
      activity, which exhibited a strong accumulation of hexoses in source leaves,
      showed pronounced phenotypical effects like stunted growth and chlorosis, and an
      undersupply of the root with carbon. Moreover, transcripts of PR (pathogenesis
      related) genes accumulated in the leaves. In these plants, mycorrhization was
      reduced. Surprisingly, plants with slightly increased leaf invertase activity
      showed a stimulation of mycorrhization, particularly 3 weeks after inoculation.
      Compared with wild-type, a higher degree of mycorrhization accompanied by a
      higher density of all fungal structures and a higher level of Glomus intraradices
      specific rRNA was detected. Those transgenic plants showed no accumulation of
      hexoses in the source leaves, minor phenotypical effects and no increased PR gene
      transcript accumulation. The roots had even lower levels of phenolic compounds
      (chlorogenic acid and scopolin), amines (such as tyramine, dopamine, octopamine
      and nicotine) and some amino acids (including 5-amino-valeric acid and 4-amino
      butyric acid), as well as an increased abscisic acid content compared with wild
      type. Minor metabolic changes were found in the leaves of these plants. The
      changes in metabolism and defense status of the plant and their putative role in
      the formation of an AM symbiosis are discussed.

PMID- 17521408
TI  - Induction of phosphatidylinositol 3-kinase-mediated endocytosis by salt stress
      leads to intracellular production of reactive oxygen species and salt tolerance.
AB  - Salt imposes immediate problems for plant cells, such as osmotic stress, impaired
      ion homeostasis and sodium toxicity, followed by a secondary oxidative stress
      caused by generation of reactive oxygen species (ROS). Here, we analyzed the
      production of ROS during salt stress. We show that salt stress triggered plasma
      membrane internalization, resulting in the production of ROS within endosomes.
      The intracellular ROS were produced by NADPH oxidase in response to the ionic but
      not the osmotic stress. Both endocytosis and ROS production were suppressed in
      phosphatidylinositol (PtdIns) 3-kinase (PI3K) mutants, PI3K being a key regulator
      of vesicle trafficking in animals and plants, and by wortmannin, which is a
      specific inhibitor of PI3K and PI4K. Endocytosis and the production of ROS were
      rescued by supplementation of seedlings with exogenous PtdIns 3-phosphate
      (PtdIns3P), less with PtdIns4P, but not with PtdIns(4,5)P(2). Surprisingly,
      despite reduced oxidative stress, the mutants and the wortmannin-treated plants
      exhibited a phenotype overly sensitive to salt, as also resulted from treatment
      with diphenyleneiodonium, a suicide inhibitor of NADPH oxidase, suggesting a
      positive role for ROS in salt tolerance. In summary, our results show that salt
      stress responses, such as increased plasma membrane endocytosis and the
      intracellular production of ROS, are coordinated by phospholipid-regulated
      signaling pathways, and suggest that ROS act in the signal transduction of the
      salt tolerance response.

PMID- 17521409
TI  - Disruption of AtOCT1, an organic cation transporter gene, affects root
      development and carnitine-related responses in Arabidopsis.
AB  - In animals, organic cation/carnitine transporters (OCTs) are involved in
      homeostasis and distribution of various small endogenous amines (e.g. carnitine,
      choline) and detoxification of xenobiotics such as nicotine. Here, we describe
      the characterization of AtOCT1, an Arabidopsis protein that shares most of the
      conserved features of mammalian plasma membrane OCTs. Transient expression of an
      AtOCT1::GFP fusion protein in onion epidermal cells and Arabidopsis protoplasts
      supported localization in the plasmalemma. AtOCT1 functionally complemented the
      Deltacit2/Deltaagp2p yeast strain that is defective in plasma membrane carnitine
      transport. Disruption of AtOCT1 in an Arabidopsis oct1-1 knockout mutant affected
      both the expression of carnitine-related genes and the developmental defects
      induced by exogenous carnitine. RT-PCR and promoter-uidA fusion analysis showed
      that AtOCT1 was expressed in vascular tissues of various organs and at sites of
      lateral root formation. Correlating with this expression pattern, oct1-1
      seedlings grown in vitro exhibited a higher degree of root branching than the
      wild-type, showing that the disruption of AtOCT1 affected root development under
      certain conditions.

PMID- 17521410
TI  - The MADS domain factors AGL15 and AGL18 act redundantly as repressors of the
      floral transition in Arabidopsis.
AB  - The developmental roles of AGL15 and AGL18, members of the AGL15-like clade of
      MADS domain regulatory factors, have not been defined previously. Analysis of
      transgenic Arabidopsis plants showed that overexpression of AGL18 produces the
      same phenotypic changes as overexpression of AGL15, and the two genes have
      partially overlapping expression patterns. Functional redundancy was confirmed
      through analysis of loss-of-function mutants. agl15 agl18 double mutants, but not
      single mutants, flower early under non-inductive conditions, indicating that
      AGL15 and AGL18 act in a redundant fashion as repressors of the floral
      transition. Further genetic analyses and expression studies were used to examine
      the relationship between AGL15 and AGL18 activity and other regulators of the
      floral transition. AGL15 and AGL18 act upstream of the floral integrator FT, and
      a combination of agl15 and agl18 mutations partially suppresses defects in the
      photoperiod pathway. agl15 agl18 mutations show an additive relationship with
      mutations in genes encoding other MADS domain floral repressors, and further
      acceleration of flowering is seen in triple and quadruple mutants under both
      inductive and non-inductive conditions. Thus, flowering time is determined by the
      additive effect of multiple MADS domain floral repressors, with important
      contributions from AGL15 and AGL18.

PMID- 17521411
TI  - Multiple loss-of-function of Arabidopsis gibberellin receptor AtGID1s completely
      shuts down a gibberellin signal.
AB  - Arabidopsis carries three receptor genes for the phytohormone gibberellin (GA),
      AtGID1a, AtGID1b and AtGID1c. Expression of each gene in the rice gid1-1 mutant
      for GA receptors causes reversion of its severely dwarfed phenotype and GA
      insensitivity to a normal level, even though each loss-of-function mutant shows
      no clear phenotype in Arabidopsis (Nakajima et al., 2006). In this paper, we
      report the functional redundancy and specificity of each AtGID1 by analyzing the
      multiple mutants for loss of function. Seeds of the double knockout mutants
      atgid1a atgid1b, atgid1a atgid1c and atgid1b atgid1c germinated normally. The
      double knockout mutant atgid1a atgid1c showed a dwarf phenotype, while other
      double mutants were of normal height compared to the wild-type. The stamens of
      the double knockout mutant atgid1a atgid1b were significantly shorter than those
      of the wild-type, and this leads to low fertility. A severe disarrangement of the
      pattern on its seed surface was also observed. The triple knockout mutant atgid1a
      atgid1b atgid1c did not germinate voluntarily, and only started to grow when the
      seed coat was peeled off after soaking. Seedlings of the triple knockout mutants
      were severe dwarfs, only a few millimeters high after growing for 1 month.
      Moreover, the triple knockout seedlings completely lost their ability to respond
      to exogenously applied GA. These results show that all AtGID1s function as GA
      receptors in Arabidopsis, but have specific role(s) for growth and development.

PMID- 17521412
TI  - The R2R3-MYB transcription factor HAG1/MYB28 is a regulator of methionine-derived
      glucosinolate biosynthesis in Arabidopsis thaliana.
AB  - Methionine-derived glucosinolates belong to a class of plant secondary
      metabolites that serve as chemoprotective compounds in plant biotic defense
      reactions and also exhibit strong anticancerogenic properties beneficial to human
      health. In a screen for the trans-activation potential of various transcription
      factors toward glucosinolate biosynthetic genes, we could identify the HAG1 (HIGH
      ALIPHATIC GLUCOSINOLATE 1, also referred to as MYB28) gene as a positive
      regulator of aliphatic methionine-derived glucosinolates. The content of
      aliphatic glucosinolates as well as transcript levels of aliphatic glucosinolate
      biosynthetic genes were elevated in gain-of-function mutants and decreased in
      HAG1 RNAi knock-down mutants. Pro(HAG1):GUS expression analysis revealed strong
      HAG1 promoter activity in generative organs and mature leaves of A. thaliana
      plants, the main sites of accumulation of aliphatic glucosinolates. Mechanical
      stimuli such as touch or wounding transiently induced HAG1/MYB28 expression in
      inflorescences of flowering plants, and HAG1/MYB28 over-expression reduced insect
      performance as revealed by weight gain assays with the generalist lepidopteran
      herbivore Spodoptera exigua. Expression of HAG1/MYB28 was significantly induced
      by glucose, indicating a novel transcriptional regulatory mechanism for the
      integration of carbohydrate availability upon biotic challenge. We hypothesize
      that HAG1/MYB28 is a novel regulator of aliphatic glucosinolate biosynthesis that
      controls the response to biotic challenges.

PMID- 17521413
TI  - Arabidopsis GH3-LIKE DEFENSE GENE 1 is required for accumulation of salicylic
      acid, activation of defense responses and resistance to Pseudomonas syringae.
AB  - In Arabidopsis, the GH3-like gene family consists of 19 members, several of which
      have been shown to adenylate the plant hormones jasmonic acid, indole acetic acid
      and salicylic acid (SA). In some cases, this adenylation has been shown to
      catalyze hormone conjugation to amino acids. Here we report molecular
      characterization of the GH3-LIKE DEFENSE GENE 1 (GDG1), a member of the GH3-like
      gene family, and show that GDG1 is an important component of SA-mediated defense
      against the bacterial pathogen Pseudomonas syringae. Expression of GDG1 is
      induced earlier and to a higher level in response to avirulent pathogens compared
      to virulent pathogens. gdg1 null mutants are compromised in several pathogen
      defense responses, including activation of defense genes and resistance against
      virulent and avirulent bacterial pathogens. Accumulation of free and glucoside
      conjugated SA (SAG) in response to pathogen infection is compromised in gdg1
      mutants. All defense-related phenotypes of gdg1 can be rescued by external
      application of SA, suggesting that gdg1 mutants are defective in the SA-mediated
      defense pathway(s) and that GDG1 functions upstream of SA. Our results suggest
      that GDG1 contributes to both basal and resistance gene-mediated inducible
      defenses against P. syringae (and possibly other pathogens) by playing a critical
      role in regulating the levels of pathogen-inducible SA. GDG1 is allelic to the
      PBS3 (avrPphB susceptible) gene.

PMID- 17521414
TI  - BEN1, a gene encoding a dihydroflavonol 4-reductase (DFR)-like protein, regulates
      the levels of brassinosteroids in Arabidopsis thaliana.
AB  - The ben1-1D (bri1-5 enhanced 1-1dominant) mutant was identified via an activation
      tagging screen for bri1-5 extragenic modifiers. bri1-5 is a weak mutant allele of
      the brassinosteroid receptor gene, BRI1. Overexpression of BEN1 greatly enhances
      the defective phenotypes of bri1-5 plants. Removal of BEN1 by gene disruption in
      a Col-0 wild-type background, on the other hand, promotes the elongation of
      organs. Because BEN1 encodes a novel protein homologous to dihydroflavonol 4
      reductase (DFR) and anthocyanidin reductase (BAN), BEN1 is probably involved in a
      brassinosteroid metabolic pathway. Analyses of brassinosteroid profiles
      demonstrated that BEN1 is indeed responsible for regulating the levels of several
      brassinosteroids, including typhasterol, castasterone and brassinolide. In vivo
      feeding and in vitro biochemical assays suggest that BEN1 is probably involved in
      a new mechanism to regulate brassinosteroid levels. These results provide
      additional insight into the regulatory mechanisms of bioactive brassinosteroids.

PMID- 17521415
TI  - Heterochromatic and genetic features are consistent with recombination
      suppression of the self-incompatibility locus in Antirrhinum.
AB  - Self-incompatibility (SI) is a genetic mechanism to prevent self-fertilization
      that is found in many species of flowering plants. Molecular studies have
      demonstrated that the S-RNase and SLF/SFB genes encoded by the single polymorphic
      S locus, which control the pollen and pistil functions of SI in three distantly
      related families, the Solanaceae, Scrophulariaceae and Rosaceae, are organized in
      a haplotype-specific manner. Previous work suggested that the haplotype structure
      of the two genes is probably maintained by recombination suppression at the S
      locus. To examine features associated with this suppression, we first mapped the
      S locus of Antirrhinum hispanicum, a member of the Scrophulariaceae, to a highly
      heterochromatic region close to the distal end of the short arm of chromosome 8.
      Both leptotene chromosome and DNA fiber fluorescence in situ hybridization
      analyses showed an obvious haplotype specificity of the Antirrhinum S locus that
      is consistent with its haplotype structure. A chromosome inversion was also
      detected around this region between A. majus and A. hispanicum. These results
      revealed that DNA sequence polymorphism and a heterochromatic location are
      associated with the S locus. Possible roles of these features in maintenance of
      the haplotype specificity involved in both self and non-self recognition are
      discussed.

PMID- 17521416
TI  - Hygienic safety of reusable tap water filters (Germlyser) with an operating time
      of 4 or 8 weeks in a haematological oncology transplantation unit.
AB  - BACKGROUND: Microbial safe tap water is crucial for the safety of
      immunosuppressed patients. METHODS: To evaluate the suitability of new, reusable
      point-of-use filters (Germlyser, Aquafree GmbH, Hamburg, Germany), three
      variations of a reusable filter with the same filter principle but with different
      outlets (with and without silver) and inner surface coating of the filter
      encasements (with and without nano-crystalline silver) were tested. The filter
      efficacy was monitored over 1, 4 and 8 weeks operating time in a haematological
      oncology transplantation unit equipped with 18 water outlets (12 taps, 6
      showers). RESULTS: The filtered water fulfilled the requirements of absence of
      pathogens over time. From 348 samples, 8 samples (2.3%) exceeded 100 cfu/ml (no
      sample > or = 500 cfu/ml). As no reprocessed filter exhibited 100% filter
      efficacy in the final quality control after each reprocessing, these
      contaminations could be explained by retrograde contamination during use.
      CONCLUSION: As a consequence of the study, the manufacturer recommends changing
      filters after 4 weeks in high risk areas and after 8 weeks in moderate infectious
      risk areas, together with routine weekly alcohol-based surface disinfection and
      additionally in case of visible contamination. The filter efficacy of the 3
      filters types did not differ significantly regarding total bacterial counts.
      Manual reprocessing proved to be insufficient. Using a validated reprocessing in
      a washer/disinfector with alkaline, acid treatment and thermic disinfection, the
      filters were effectively reprocessable and now provide tap water meeting the
      German drinking water regulations as well as the WHO guidelines, including
      absence of pathogens.

PMID- 17521417
TI  - Widespread pyocyanin over-production among isolates of a cystic fibrosis epidemic
      strain.
AB  - BACKGROUND: Some isolates of the Liverpool cystic fibrosis epidemic strain of
      Pseudomonas aeruginosa exhibit an unusual virulence-related phenotype,
      characterized by over-production of quorum sensing-regulated exoproducts such as
      pyocyanin and LasA protease. Our aim was to determine the prevalence of this
      unusual phenotype amongst isolates of the epidemic strain, and to study other
      intraclonal phenotypic and genotypic variations. RESULTS: The unusual phenotype
      was detected in at least one epidemic strain isolate from the majority of cystic
      fibrosis patients tested, and can be retained for up to seven years during
      chronic infection. Multiple sequential isolates of the epidemic strain taken from
      six patients over a period of up to nine years exhibited a wide range of
      phenotypes, including different antimicrobial susceptibilities. Our data suggest
      that each sputum sample contains a mixture of phenotypes and genotypes within the
      epidemic strain population, including within colony morphotypes. Many isolates
      exhibit premature (during early rather than late exponential growth) and over
      production of pyocyanin, which has a number of toxic effects directly relevant to
      cystic fibrosis. CONCLUSION: The widespread occurrence of this unusual phenotype
      suggests that it may play an important role in the success of the epidemic
      strain.

PMID- 17521418
TI  - Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog
      brain.
AB  - BACKGROUND: Narcolepsy causes dramatic behavioral alterations in both humans and
      dogs, with excessive sleepiness and cataplexy triggered by emotional stimuli.
      Deficiencies in the hypocretin system are well established as the origin of the
      condition; both from studies in humans who lack the hypocretin ligand (HCRT) and
      in dogs with a mutation in hypocretin receptor 2 (HCRTR2). However, little is
      known about molecular alterations downstream of the hypocretin signals. RESULTS:
      By using microarray technology we have screened the expression of 29760 genes in
      the brains of Doberman dogs with a heritable form of narcolepsy (homozygous for
      the canarc-1 [HCRTR-2-2] mutation), and their unaffected heterozygous siblings.
      We identified two neuropeptide precursor molecules, Tachykinin precursor 1 (TAC1)
      and Proenkephalin (PENK), that together with Suppressor of cytokine signaling 2
      (SOCS2), showed reduced expression in narcoleptic brains. The difference was
      particularly pronounced in the amygdala, where mRNA levels of PENK were 6.2 fold
      lower in narcoleptic dogs than in heterozygous siblings, and TAC1 and SOCS2
      showed 4.4 fold and 2.8 fold decrease in expression, respectively. The results
      obtained from microarray experiments were confirmed by real-time RT-PCR.
      Interestingly, it was previously shown that a single dose of amphetamine-like
      stimulants able to increase wakefulness in the dogs, also produce an increase in
      the expression of both TAC1 and PENK in mice. CONCLUSION: These results suggest
      that TAC1, PENK and SOCS2 might be intimately connected with the excessive
      daytime sleepiness not only in dogs, but also in other species, possibly
      including humans.

PMID- 17521419
TI  - GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis
      metabolism.
AB  - BACKGROUND: An impediment to the rational development of novel drugs against
      tuberculosis (TB) is a general paucity of knowledge concerning the metabolism of
      Mycobacterium tuberculosis, particularly during infection. Constraint-based
      modeling provides a novel approach to investigating microbial metabolism but has
      not yet been applied to genome-scale modeling of M. tuberculosis. RESULTS: GSMN
      TB, a genome-scale metabolic model of M. tuberculosis, was constructed,
      consisting of 849 unique reactions and 739 metabolites, and involving 726 genes.
      The model was calibrated by growing Mycobacterium bovis bacille Calmette Guerin
      in continuous culture and steady-state growth parameters were measured. Flux
      balance analysis was used to calculate substrate consumption rates, which were
      shown to correspond closely to experimentally determined values. Predictions of
      gene essentiality were also made by flux balance analysis simulation and were
      compared with global mutagenesis data for M. tuberculosis grown in vitro. A
      prediction accuracy of 78% was achieved. Known drug targets were predicted to be
      essential by the model. The model demonstrated a potential role for the enzyme
      isocitrate lyase during the slow growth of mycobacteria, and this hypothesis was
      experimentally verified. An interactive web-based version of the model is
      available. CONCLUSION: The GSMN-TB model successfully simulated many of the
      growth properties of M. tuberculosis. The model provides a means to examine the
      metabolic flexibility of bacteria and predict the phenotype of mutants, and it
      highlights previously unexplored features of M. tuberculosis metabolism.

PMID- 17521420
TI  - A systematic comparative and structural analysis of protein phosphorylation sites
      based on the mtcPTM database.
AB  - mtcPTM is an online repository of human and mouse phosphosites in which data are
      hierarchically organized to preserve biologically relevant experimental
      information, thus allowing straightforward comparisons of phosphorylation
      patterns found under different conditions. The database also contains the largest
      available collection of atomic models of phosphorylatable proteins. Detailed
      analysis of this structural dataset reveals that phosphorylation sites are found
      in a heterogeneous range of structural and sequence contexts. mtcPTM is available
      on the web http://www.mitocheck.org/cgi-bin/mtcPTM/search.

PMID- 17521421
TI  - High synovial expression of the inhibitory FcgammaRIIb in rheumatoid arthritis.
AB  - Activating Fc gamma receptors (FcgammaRs) have been identified as having
      important roles in the inflammatory joint reaction in rheumatoid arthritis (RA)
      and murine models of arthritis. However, the role of the inhibitory FcgammaRIIb
      in the regulation of the synovial inflammation in RA is less known. Here we have
      investigated synovial tissue from RA patients using a novel monoclonal antibody
      (GB3) specific for the FcgammaRIIb isoform. FcgammaRIIb was abundantly expressed
      in synovia of RA patients, in sharp contrast to the absence or weak staining of
      FcgammaRIIb in synovial biopsies from healthy volunteers. In addition, the
      expression of FcgammaRI, FcgammaRII and FcgammaRIII was analyzed in synovia
      obtained from early and late stages of RA. Compared with healthy synovia, which
      expressed FcgammaRII, FcgammaRIII but not FcgammaRI, all activating FcgammaRs
      were expressed and significantly up-regulated in RA, regardless of disease
      duration. Macrophages were one of the major cell types in the RA synovium
      expressing FcgammaRIIb and the activating FcgammaRs. Anti-inflammatory treatment
      with glucocorticoids reduced FcgammaR expression in arthritic joints,
      particularly that of FcgammaRI. This study demonstrates for the first time that
      RA patients do not fail to up-regulate FcgammaRIIb upon synovial inflammation,
      but suggests that the balance between expression of the inhibitory FcgammaRIIb
      and activating FcgammaRs may be in favour of the latter throughout the disease
      course. Anti-inflammatory drugs that target activating FcgammaRs may represent
      valuable therapeutics in this disease.

PMID- 17521422
TI  - Proton-pump inhibitors are associated with a reduced risk for bleeding and
      perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory
      drugs: a nested case-control study.
AB  - Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by
      gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The
      efficacy of proton-pump inhibitors in the primary prevention of ulcer
      complications arising from the use of NSAIDs remains unproven. Selective
      cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but
      not completely in high-risk patients. This study determines which patients are
      especially at risk for NSAID ulcer complications and investigates the
      effectiveness of different preventive strategies in daily clinical practice. With
      the use of a nested case-control design, a large cohort of NSAID users was
      followed for 26 months. Cases were patients with NSAID ulcer complications
      necessitating hospitalisation; matched controls were selected from the remaining
      cohort of NSAID users who did not have NSAID ulcer complications. During the
      observational period, 104 incident cases were identified from a cohort of 51,903
      NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of
      NSAID use, age at diagnosis 70.4 +/- 16.7 years (mean +/- SD), 55.8% women), and
      284 matched controls. Cases were characterised by serious, especially
      cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer
      complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant
      proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with
      a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95%
      confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer
      complications are elderly patients with cardiovascular co-morbidity. Proton-pump
      inhibitors are associated with a reduced risk for NSAID ulcer complications.

PMID- 17521423
TI  - Comparing segmentations by applying randomization techniques.
AB  - BACKGROUND: There exist many segmentation techniques for genomic sequences, and
      the segmentations can also be based on many different biological features. We
      show how to evaluate and compare the quality of segmentations obtained by
      different techniques and alternative biological features. RESULTS: We apply
      randomization techniques for evaluating the quality of a given segmentation. Our
      example applications include isochore detection and the discovery of coding
      noncoding structure. We obtain segmentations of relevant sequences by applying
      different techniques, and use alternative features to segment on. We show that
      some of the obtained segmentations are very similar to the underlying true
      segmentations, and this similarity is statistically significant. For some other
      segmentations, we show that equally good results are likely to appear by chance.
      CONCLUSION: We introduce a framework for evaluating segmentation quality, and
      demonstrate its use on two examples of segmental genomic structures. We transform
      the process of quality evaluation from simply viewing the segmentations, to
      obtaining p-values denoting significance of segmentation similarity.

PMID- 17521424
TI  - In vitro activities of 18 antimicrobial agents against Staphylococcus aureus
      isolates from the Institut Pasteur of Madagascar.
AB  - BACKGROUND: Staphylococcus aureus, one of the most frequently isolated pathogens
      in both hospitals and the community, has been particularly efficient at
      developing resistance to antimicrobial agents. In developed countries, as
      methicillin-resistant S. aureus (MRSA) has prevailed and, furthermore, as S.
      aureus with reduced susceptibility to vancomycin has emerged, the therapeutic
      options for the treatment of S. aureus infections have become limited. In
      developing countries and especially African countries very little is known
      concerning the resistance of S. aureus to antibiotics. In Madagascar no data
      exist concerning this resistance. OBJECTIVE: To update the current status of
      antibiotic resistance of S. aureus in Antananarivo, Madagascar. METHODS: Clinical
      S. aureus isolates were collected from patients at the Institut Pasteur of
      Madagascar from January 2001 to December 2005. Susceptibility tests with 18
      antibiotics were performed by the disk diffusion method. RESULTS: Among a total
      of 574 isolates, 506 were from community-acquired infections and 68 from
      nosocomial infections. There was no significant difference in the methicillin
      resistance rate between community-acquired strains (33 of 506; 6.5%) and
      nosocomial strains (3 of 68, 4.4%). Many MRSA isolates were resistant to multiple
      classes of antibiotics. Resistance to tetracyclin, trimethoprim-sulfamethoxazole
      and erythromycin was more common. Among MRSA isolates resistance rates to
      rifampicin, fusidic acid, gentamicin and ciprofloxacin were lower than that
      observed with other drugs easily available in Madagascar. No isolates were
      resistant to glycopeptides. CONCLUSION: The rate of methicillin-resistant S.
      aureus is not different between community-acquired and nosocomial infections and
      is still rather low in Madagascar.

PMID- 17521425
TI  - Selective activation of TCR-gammadelta+ cells in endemic Burkitt's lymphoma.
AB  - BACKGROUND: The overlap in geographical distribution of Plasmodium falciparum
      malaria and endemic Burkitt's lymphoma (eBL)--an aggressive Epstein-Barr virus
      (EBV)-associated B-cell tumour occurring almost exclusively in the tropics-
      strongly suggests a link between the two diseases. It is suspected that the
      polyclonal B-cell activation in P. falciparum malaria may precipitate a breakdown
      in homeostatic T-cell control of EBV-immortalized B-cell proliferation. Previous
      studies have suggested that a particular T-cell subset, characterized by
      expression of Vdelta1+ gammadelta T-cell receptors, is important for maintaining
      B-cell homeostasis, both in P. falciparum- exposed populations and in individuals
      subject to polyclonal B-cell activation of other aetiology. The objective of the
      present study was, therefore, to characterize lymphocyte phenotypes and to
      investigate possible differences in T-cell subset composition and activation
      status in P. falciparum-exposed Ghanaian children with and without eBL. METHODS:
      Venous blood samples in heparin from 21 eBL patients (mean age: 7.0 years; range:
      3-11 years), referred to the Burkitt's Tumour Centre at Korle-Bu Teaching
      Hospital, Accra and 15 healthy, age and sex matched children, were stained with
      fluorescein isothiocyanate (FITC)-, phycoerythrin (PE)-, R-phycoerythrin (RPE)-
      and RPE-Cy5-conjugated antibodies (CD3, CD4, CD8, CD25, CD69, CD95, HLA-DR, TCR
      gammadelta, Vdelta1, Vdelta3, Vgamma9 and B-cells) and acquired on a flow
      cytometer. RESULTS: A reduction in the proportion of CD3+ cells in eBL patients,
      due mainly to perturbations among TCR-gammadelta+ cells was observed. In
      contrast, the proportions of CD4+ or CD8+ cells were relatively unaffected, as
      were the mean numbers of peripheral blood mononuclear cells. CONCLUSION:
      Selective changes in numbers and activation status of TCR-gammadelta+ cells
      occurs in Ghanaian children with eBL, a pattern which is similar to P. falciparum
      induced changes. The data supports the hypothesis of a regulatory role for
      Vdelta1+ TcR-gammadelta T-cells in maintaining B-cell homeostasis and provides
      insights into the pathogenesis of eBL.

PMID- 17521426
TI  - Complex distribution of EFL and EF-1alpha proteins in the green algal lineage.
AB  - BACKGROUND: EFL (or elongation factor-like) is a member of the translation
      superfamily of GTPase proteins. It is restricted to eukaryotes, where it is found
      in a punctate distribution that is almost mutually exclusive with elongation
      factor-1 alpha (EF-1alpha). EF-1alpha is a core translation factor previously
      thought to be essential in eukaryotes, so its relationship to EFL has prompted
      the suggestion that EFL has spread by horizontal or lateral gene transfer (HGT or
      LGT) and replaced EF-1alpha multiple times. Among green algae, trebouxiophyceans
      and chlorophyceans have EFL, but the ulvophycean Acetabularia and the sister
      group to green algae, land plants, have EF-1alpha. This distribution singles out
      green algae as a particularly promising group to understand the origin of EFL and
      the effects of its presence on EF-1alpha. RESULTS: We have sampled all major
      lineages of green algae for both EFL and EF-1alpha. EFL is unexpectedly broad in
      its distribution, being found in all green algal lineages (chlorophyceans,
      trebouxiophyceans, ulvophyceans, prasinophyceans, and mesostigmatophyceans),
      except charophyceans and the genus Acetabularia. The presence of EFL in the genus
      Mesostigma and EF-1alpha in Acetabularia are of particular interest, since the
      opposite is true of all their closest relatives. The phylogeny of EFL is poorly
      resolved, but the Acetabularia EF-1alpha is clearly related to homologues from
      land plants and charophyceans, demonstrating that EF-1alpha was present in the
      common ancestor of the green lineage. CONCLUSION: The distribution of EFL and EF
      1alpha in the green lineage is not consistent with the phylogeny of the
      organisms, indicating a complex history of both genes. Overall, we suggest that
      after the introduction of EFL (in the ancestor of green algae or earlier), both
      genes co-existed in green algal genomes for some time before one or the other was
      lost on multiple occasions.

PMID- 17521427
TI  - Leptin induces inflammation-related genes in RINm5F insulinoma cells.
AB  - BACKGROUND: Leptin acts not only on hypothalamic centers to control food intake
      but has additional functions in peripheral tissues, e.g. inhibition of insulin
      secretion from pancreatic islets. The leptin receptor (LEPRb) is a class I
      cytokine receptor that mediates activation of STAT transcription factors. In this
      study, we characterise the regulation of inflammation-related genes by leptin in
      insulinoma cells and compare the effect of transcriptional regulation by leptin
      with that of other cytokines. RESULTS: We have used RINm5F insulinoma cells as a
      model system for a peripheral target cell of leptin. Six transcripts encoding
      inflammation-related proteins were found to be upregulated by activation of
      LEPRb, namely lipocalin-2, pancreatitis-associated protein, preprotachykinin-1,
      fibrinogen-beta, tissue-type plasminogen activator (tPA) and manganese-dependent
      superoxide dismutase (MnSOD). Four of these transcripts (fibrinogen-beta,
      lipocalin-2, tPA, MnSOD) were also induced by the proinflammatory cytokine
      interleukin-1beta (IL-1beta). Interferon-gamma alone had no effect on the leptin
      induced transcripts but enhanced the upregulation by IL-1beta of lipocalin-2, tPA
      and MnSOD mRNA levels. Experiments with LEPRb point mutants revealed that the
      upregulation of the inflammation-related genes depended on the presence of
      tyrosine-1138 which mediates the activation of the transcription factors STAT1
      and STAT3. Reporter gene assays showed that leptin induced the expression of
      preprotachykinin-1 and lipocalin-2 on the level of promoter regulation. Finally,
      leptin treatment increased caspase 3-like proteolytic activity in RINm5F cells.
      CONCLUSION: The present data show that leptin induces a cytokine-like
      transcriptional response in RINm5F cells, consistent with the proposed function
      of leptin as a modulator of immune and inflammatory responses.

PMID- 17521428
TI  - Three novel ABCC5 splice variants in human retina and their role as regulators of
      ABCC5 gene expression.
AB  - BACKGROUND: The ABCC5 gene encodes an organic anion pump of the ATP-binding
      cassette (ABC) transporter family, subclass C. The exact physiological function
      of ABCC5 however is not known. Here, we have isolated three novel ABCC5 splice
      variants and characterized their role in the regulation of ABCC5 gene expression.
      RESULTS: Two additional exons within intron 5 of the ABCC5 gene were identified;
      one of the exons exhibits alternative donor splice sites. Differential usage of
      these exons generates three short ABCC5 transcripts named ABCC5_SV1, ABCC5_SV2
      and ABCC5_SV3. The variants share the first five exons with the ABCC5 gene but
      differ in their 3' sequences. ABCC5 and its novel isoforms are abundantly
      expressed in the human retina. Splice variant ABCC5_SV1 and ABCC5_SV2 contain
      premature stop codons. While inhibition of nonsense-mediated mRNA decay
      selectively stabilized ABCC5_SV1 but not ABCC5_SV2, the amount of full length
      ABCC5 mRNA was simultaneously reduced. A negative regulatory effect on full
      length ABCC5 expression was also observed when the ABCC5 isoforms were silenced
      with siRNA duplexes. Finally, we show that the evolutionarily conserved ABCC5_SV2
      transcript is translated into a protein abundantly present in endothelial cells
      of inner retinal blood vessels and along RPE membranes. CONCLUSION: Our data
      suggest that alternative splicing of the ABCC5 gene has functional consequences
      by modulating ABCC5 gene expression. In addition, at least one ABCC5 splice
      variant is protein-coding and produces a truncated ABCC5 protein isoform with
      thus far unknown functional properties in the retina.

PMID- 17521429
TI  - Altered collecting duct adenylyl cyclase content in collecting duct endothelin-1
      knockout mice.
AB  - BACKGROUND: Endothelin-1 (ET-1) inhibition of vasopressin (AVP)-stimulated water
      reabsorption by the inner medullary collecting duct (IMCD) is associated with
      reduced cAMP accumulation. To determine the effect of ET-1 deficiency, AVP
      stimulated cAMP responsiveness was assessed in IMCD from mice with collecting
      duct-specific deletion of ET-1 (CD ET-1 KO) and from control animals. METHODS:
      Cyclic AMP production, adenylyl cyclase (AC) mRNA, and AC protein were measured
      in acutely isolated IMCD. RESULTS: CD ET-1 KO IMCD had enhanced AVP-stimulated
      cAMP accumulation. Inhibition of calcium-stimulated AC using BAPTA did not
      prevent enhanced AVP responsiveness in CD ET-1 KO IMCD. Factors known to be
      modified by ET-1, including nitric oxide, cyclooxygenase metabolites, and
      superoxide did not affect the increased AVP responsiveness of CD ET-1 KO IMCD.
      Differential V2 receptor or G-protein activity was not involved since CD ET-1 KO
      IMCD had increased cAMP accumulation in response to forskolin and/or cholera
      toxin. CD ET-1 KO did not affect mRNA or protein levels of AC3, one of the major
      known collecting duct AC isoforms. However, the other known major collecting duct
      AC isoform (AC5/6) did have increased protein levels in CD ET-1 KO IMCD, although
      AC5 (weak signal) and 6 mRNA levels were unchanged. CONCLUSION: ET-1 deficiency
      increases IMCD AC5/6 content, an effect that may synergize with acute ET-1
      inhibition of AVP-stimulated cAMP accumulation.

PMID- 17521430
TI  - Serum procalcitonin measurement as diagnostic and prognostic marker in febrile
      adult patients presenting to the emergency department.
AB  - INTRODUCTION: Identification of bacterial infections is crucial if treatment is
      to be initiated early and antibiotics used rationally. The primary objective of
      this study was to test the efficiency of procalcitonin (PCT) in identifying
      bacterial/parasitic episodes among febrile adult patients presenting to an
      emergency department. Secondary objectives were to identify clinical or
      biological variables associated with either bacterial/parasitic infection or
      critical illness. METHODS: This was a prospective, single centre, non
      interventional study, conducted in the adult emergency department of an academic
      tertiary care hospital. We included patients with body temperature of 38.5
      degrees C or greater. A serum sample for measurement of PCT was collected in the
      emergency room. Patients were followed up until day 30. After reviewing the
      medical files, two independent experts, who were blind to the PCT results,
      classified each of the patients as having a bacterial/parasitic infection, viral
      infection, or another diagnosis. RESULTS: Among 243 patients included in the
      study, 167 had bacterial/parasitic infections, 35 had viral infections and 41 had
      other diagnoses. The PCT assay, with a 0.2 microg/l cutoff value, had a
      sensitivity of 0.77 and a specificity of 0.59 in diagnosing bacterial/parasitic
      infection. Of the patients with PCT 5 microg/l or greater, 51% had critical
      illness (death or intensive care unit admission) as compared with 13% of patients
      with lower PCT values. CONCLUSION: Bearing in mind the limitations of an
      observational study design, the judgements of the emergency department physicians
      were reasonably accurate in determining the pretest probability of
      bacterial/parasitic infection. PCT may provide additional, valuable information
      on the aetiology and prognosis of infection in the emergency department.

PMID- 17521431
TI  - Could a simple antenatal package combining micronutritional supplementation with
      presumptive treatment of infection prevent maternal deaths in sub-Saharan Africa?
AB  - BACKGROUND: Reducing maternal mortality is a key goal of international
      development. Our objective was to determine the potential impact on maternal
      mortality across sub-Saharan Africa of a combination of dietary supplementation
      and presumptive treatment of infection during pregnancy. Our aim was to
      demonstrate the importance of antenatal interventions in the fight against
      maternal mortality, and to stimulate debate about the design of an effective
      antenatal care package which could be delivered at the lowest level of the
      antenatal health system or at community level. METHODS: We collated evidence for
      the effectiveness of antenatal interventions from systematic reviews and
      controlled trials, and we selected interventions which have demonstrated
      potential to prevent maternal deaths. We used a model-based analysis to estimate
      the total reduction in maternal mortality in sub-Saharan Africa which could be
      achieved by combining these interventions into a single package, based on a WHO
      systematic review of causes of maternal deaths. RESULTS: Severe hypertensive
      disorders, puerperal sepsis and anemia are causes of maternal deaths which could
      be prevented to some extent by prophylactic measures during pregnancy. A package
      of pills comprising calcium and iron supplements and appropriate anti-microbial
      and anti-malarial drugs could reduce maternal mortality in sub-Saharan Africa by
      8% (range <1% to 20%). This estimate is based on Cochrane Review estimates for
      the effectiveness of daily calcium supplements in reducing the risk of
      death/serious morbidity due to hypertensive disorders (RR = 0.80, 95% CI 0.65
      0.97), anti-microbial prophylaxis in reducing the odds of puerperal
      sepsis/postpartum endometritis (OR = 0.49, 95% CI 0.23-1.06), anti-malarial
      prophylaxis in reducing the risk of severe antenatal anemia (RR = 0.62, 95% CI
      0.50-0.78), and iron supplementation in reducing the risk of iron deficiency
      anemia at term (RR = 0.33, 95% CI 0.16-0.69). CONCLUSION: Maternal mortality
      could be reduced by a combination of micronutrient supplementation and
      presumptive treatment of infection during pregnancy. Such an approach could be
      adopted in resource-poor settings where visits to antenatal clinics are
      infrequent and would complement existing Safe Motherhood activities.

PMID- 17521432
TI  - Metabolic compartmentalization in the human cortex and hippocampus: evidence for
      a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate
      dehydrogenase.
AB  - BACKGROUND: For a long time now, glucose has been thought to be the main, if not
      the sole substrate for brain energy metabolism. Recent data nevertheless suggest
      that other molecules, such as monocarboxylates (lactate and pyruvate mainly)
      could be suitable substrates. Although monocarboxylates poorly cross the blood
      brain barrier (BBB), such substrates could replace glucose if produced locally.
      The two key enzymatiques systems required for the production of these
      monocarboxylates are lactate dehydrogenase (LDH; EC1.1.1.27) that catalyses the
      interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex
      that irreversibly funnels pyruvate towards the mitochondrial TCA and oxydative
      phosphorylation. RESULTS: In this article, we show, with monoclonal antibodies
      applied to post-mortem human brain tissues, that the typically glycolytic
      isoenzyme of lactate dehydrogenase (LDH-5; also called LDHA or LDHM) is
      selectively present in astrocytes, and not in neurons, whereas pyruvate
      dehydrogenase (PDH) is mainly detected in neurons and barely in astrocytes. At
      the regional level, the distribution of the LDH-5 immunoreactive astrocytes is
      laminar and corresponds to regions of maximal 2-deoxyglucose uptake in the
      occipital cortex and hippocampus. In hippocampus, we observed that the
      distribution of the oxidative enzyme PDH was enriched in the neurons of the
      stratum pyramidale and stratum granulosum of CA1 through CA4, whereas the
      glycolytic enzyme LDH-5 was enriched in astrocytes of the stratum moleculare, the
      alveus and the white matter, revealing not only cellular, but also regional,
      selective distributions. The fact that LDH-5 immunoreactivity was high in
      astrocytes and occurred in regions where the highest uptake of 2-deoxyglucose was
      observed suggests that glucose uptake followed by lactate production may
      principally occur in these regions. CONCLUSION: These observations reveal a
      metabolic segregation, not only at the cellular but also at the regional level,
      that support the notion of metabolic compartmentalization between astrocytes and
      neurons, whereby lactate produced by astrocytes could be oxidized by neurons.

PMID- 17521433
TI  - Rapid evolution of cancer/testis genes on the X chromosome.
AB  - BACKGROUND: Cancer/testis (CT) genes are normally expressed only in germ cells,
      but can be activated in the cancer state. This unusual property, together with
      the finding that many CT proteins elicit an antigenic response in cancer
      patients, has established a role for this class of genes as targets in
      immunotherapy regimes. Many families of CT genes have been identified in the
      human genome, but their biological function for the most part remains unclear.
      While it has been shown that some CT genes are under diversifying selection, this
      question has not been addressed before for the class as a whole. RESULTS: To shed
      more light on this interesting group of genes, we exploited the generation of a
      draft chimpanzee (Pan troglodytes) genomic sequence to examine CT genes in an
      organism that is closely related to human, and generated a high-quality, manually
      curated set of human:chimpanzee CT gene alignments. We find that the chimpanzee
      genome contains homologues to most of the human CT families, and that the genes
      are located on the same chromosome and at a similar copy number to those in
      human. Comparison of putative human:chimpanzee orthologues indicates that CT
      genes located on chromosome X are diverging faster and are undergoing stronger
      diversifying selection than those on the autosomes or than a set of control genes
      on either chromosome X or autosomes. CONCLUSION: Given their high level of
      diversifying selection, we suggest that CT genes are primarily responsible for
      the observed rapid evolution of protein-coding genes on the X chromosome.

PMID- 17521434
TI  - Novel in vivo targets of DeltaNp63 in keratinocytes identified by a modified
      chromatin immunoprecipitation approach.
AB  - BACKGROUND: p63 is a transcription factor that plays an important role in skin
      epidermal development and differentiation. The p63 gene encodes for two major
      protein isoforms, those containing an amino-terminal trans-activation domain
      (TAp63) and those lacking this domain (DeltaNp63). Both the TA and DeltaN
      transcripts are also alternatively spliced at the 3' end producing proteins with
      unique C-termini that are designated as alpha, beta and gamma isoforms. Recent
      research has suggested that DeltaNp63 is the predominant isoform expressed and
      active in keratinocytes. RESULTS: To better elucidate the biological role of p63
      in regulating gene expression in keratinocytes we performed chromatin
      immunoprecipitation (ChIP) experiments with DeltaNp63-specific antibodies. We
      included an additional step in the ChIP procedure to enrich for DeltaNp63 targets
      by screening the library of immunoprecipitated DNA for its ability to bind
      recombinant GST-DeltaNp63. Cloning of DeltaNp63-ChIP-derived DNA fragments
      identified more than 60 potential DeltaNp63 target loci that were located close
      to or embedded within known or predicted genes. Identity of these target genes
      suggests that they may participate in a myriad of cellular processes including
      transcriptional regulation, signaling and metabolism. Here we confirm the binding
      of DeltaNp63 to several of these genomic loci both by EMSA and replicate ChIP
      assays. Finally we show that the expression of many of these target genes is
      altered when DeltaNp63 levels in keratinocytes are reduced by siRNA, further
      confirming that these are bona fide targets. CONCLUSION: This unbiased genomic
      approach has allowed us to uncover functional targets of DeltaNp63 and serves as
      the initial step in further analysis of the transcriptional regulatory mechanisms
      that are governed by p63 in keratinocytes.

PMID- 17521435
TI  - Risk factors for development of non-specific musculoskeletal pain in preteens and
      early adolescents: a prospective 1-year follow-up study.
AB  - BACKGROUND: Musculoskeletal pain symptoms are common in children and adolescents.
      These symptoms have a negative impact on children's physical and emotional well
      being, but their underlying aetiology and risk factors are still poorly
      understood. Most of the previous cohort studies were conducted among mid and/or
      late adolescents and were mainly focused on a specific pain location (e.g. low
      back pain or neck pain). The purpose of this study is to estimate occurrence of
      new-onset pain symptoms, in all musculoskeletal locations, in preteens and early
      adolescents and investigate risk factors for development of these symptoms.
      METHODS: 1756 schoolchildren (mean age 10.8) were recruited from schools in
      southern Finland. Information was extracted as to whether they experienced
      musculoskeletal pain and a total of 1192 children were identified as free of
      musculoskeletal pain symptoms. Information was collected on factors which could
      potentially predict the development of musculoskeletal pain: headache, abdominal
      pain, sadness/feeling down, day-time tiredness, difficulty in falling asleep,
      waking up during nights, level of physical activity and hypermobility. These
      children were followed-up 1-year later and those with new episodes of non
      traumatic and traumatic musculoskeletal pain symptoms were identified. RESULTS: A
      total of 1113 schoolchildren (93% of baseline pain-free children) were found at
      one-year follow-up. New episodes of musculoskeletal pain were reported by 21.5%
      of these children. Of them 19.4% reported non-traumatic pain and 4.0% reported
      traumatic pain. The neck was the most commonly reported site with non-traumatic
      pain, while the lower limb was the most common site for traumatic pain. The
      independent risk factors for non-traumatic musculoskeletal pain were headache (OR
      = 1.68, [95% CI 1.16-2.44]) and day-time tiredness (OR = 1.53, [95% CI 1.03
      2.26]). The risk factors for traumatic musculoskeletal pain were vigorous
      exercise (OR = 3.40 [95% CI 1.39-8.31]) and day-time tiredness (OR = 2.97 [95% CI
      1.41-6.26]). CONCLUSION: This study highlights that there may be two types of
      pain entities with both distinct and common aspects of aetiology. For primary
      prevention purposes, school healthcare professionals should pay attention to
      preteens and early adolescents practicing vigorous exercise (predictor of
      traumatic pain), reporting headache (predictor of non-traumatic pain) and
      reporting day-time tiredness (predictor of both types of pain).

PMID- 17521436
TI  - Differential expression of the capsaicin receptor TRPV1 and related novel
      receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic
      and diabetic neuropathy.
AB  - BACKGROUND: Transient receptor potential (TRP) receptors expressed by primary
      sensory neurons mediate thermosensitivity, and may play a role in sensory
      pathophysiology. We previously reported that human dorsal root ganglion (DRG)
      sensory neurons co-expressed TRPV1 and TRPV3, and that these were increased in
      injured human DRG. Related receptors TRPV4, activated by warmth and eicosanoids,
      and TRPM8, activated by cool and menthol, have been characterised in pre-clinical
      models. However, the role of TRPs in common clinical sensory neuropathies needs
      to be established. METHODS: We have studied TRPV1, TRPV3, TRPV4, and TRPM8 in
      nerves (n = 14) and skin from patients with nerve injury, avulsed dorsal root
      ganglia (DRG) (n = 11), injured spinal nerve roots (n = 9), diabetic neuropathy
      skin (n = 8), non-diabetic neuropathic nerve biopsies (n = 6), their respective
      control tissues, and human post mortem spinal cord, using immunohistological
      methods. RESULTS: TRPV1 and TRPV3 were significantly increased in injured
      brachial plexus nerves, and TRPV1 in hypersensitive skin after nerve repair,
      whilst TRPV4 was unchanged. TRPM8 was detected in a few medium diameter DRG
      neurons, and was unchanged in DRG after avulsion injury, but was reduced in axons
      and myelin in injured nerves. In diabetic neuropathy skin, TRPV1 expressing sub-
      and intra-epidermal fibres were decreased, as was expression in surviving fibres.
      TRPV1 was also decreased in non-diabetic neuropathic nerves. Immunoreactivity for
      TRPV3 was detected in basal keratinocytes, with a significant decrease of TRPV3
      in diabetic skin. TRPV1-immunoreactive nerves were present in injured dorsal
      spinal roots and dorsal horn of control spinal cord, but not in ventral roots,
      while TRPV3 and TRPV4 were detected in spinal cord motor neurons. CONCLUSION: The
      accumulation of TRPV1 and TRPV3 in peripheral nerves after injury, in spared
      axons, matches our previously reported changes in avulsed DRG. Reduction of TRPV1
      levels in nerve fibres in diabetic neuropathy skin may result from the known
      decrease of nerve growth factor (NGF) levels. The role of TRPs in keratinocytes
      is unknown, but a relationship to changes in NGF levels, which is produced by
      keratinocytes, deserves investigation. TRPV1 represents a more selective
      therapeutic target than other TRPs for pain and hypersensitivity, particularly in
      post-traumatic neuropathy.

PMID- 17521437
TI  - Drug susceptibility testing of clinical isolates of streptococci and enterococci
      by the Phoenix automated microbiology system.
AB  - BACKGROUND: Drug resistance is an emerging problem among streptococcal and
      enterococcal species. Automated diagnostic systems for species identification and
      antimicrobial susceptibility testing (AST) have become recently available. We
      evaluated drug susceptibility of clinical isolates of streptococci and
      enterococci using the recent Phoenix system (BD, Sparks, MD). Diagnostic tools
      included the new SMIC/ID-2 panel for streptococci, and the PMIC/ID-14 for
      enterococci. Two-hundred and fifty isolates have been investigated: beta
      hemolytic streptococci (n = 65), Streptococcus pneumoniae (n = 50), viridans
      group streptococci (n = 32), Enterococcus faecium (n = 40), Enterococcus faecalis
      (n = 43), other catalase-negative cocci (n = 20). When needed, species ID was
      determined using molecular methods. Test bacterial strains were chosen among
      those carrying clinically-relevant resistance determinants (penicillin,
      macrolides, fluoroquinolones, glycopeptides). AST results of the Phoenix system
      were compared to minimal inhibitory concentration (MIC) values measured by the
      Etest method (AB Biodisk, Solna, Sweden). RESULTS: Streptococci: essential
      agreement (EA) and categorical agreement (CA) were 91.9% and 98.8%, respectively.
      Major (ME) and minor errors (mE) accounted for 0.1% and 1.1% of isolates,
      respectively. No very major errors (VME) were produced. Enterococci: EA was 97%,
      CA 96%. Small numbers of VME (0.9%), ME (1.4%) and mE (2.8%) were obtained.
      Overall, EA and CA rates for most drugs were above 90% for both genera. A few VME
      were found: a) teicoplanin and high-level streptomycin for E. faecalis, b) high
      level gentamicin for E. faecium. The mean time to results (+/- SD) was 11.8 +/-
      0.9 h, with minor differences between streptococci and enterococci. CONCLUSION:
      The Phoenix system emerged as an effective tool for quantitative AST. Panels
      based on dilution tests provided rapid and accurate MIC values with regard to
      clinically-relevant streptococcal and enterococcal species.

PMID- 17521438
TI  - The CRISPRdb database and tools to display CRISPRs and to generate dictionaries
      of spacers and repeats.
AB  - BACKGROUND: In Archeae and Bacteria, the repeated elements called CRISPRs for
      "clustered regularly interspaced short palindromic repeats" are believed to
      participate in the defence against viruses. Short sequences called spacers are
      stored in-between repeated elements. In the current model, motifs comprising
      spacers and repeats may target an invading DNA and lead to its degradation
      through a proposed mechanism similar to RNA interference. Analysis of intra
      species polymorphism shows that new motifs (one spacer and one repeated element)
      are added in a polarised fashion. Although their principal characteristics have
      been described, a lot remains to be discovered on the way CRISPRs are created and
      evolve. As new genome sequences become available it appears necessary to develop
      automated scanning tools to make available CRISPRs related information and to
      facilitate additional investigations. DESCRIPTION: We have produced a program,
      CRISPRFinder, which identifies CRISPRs and extracts the repeated and unique
      sequences. Using this software, a database is constructed which is automatically
      updated monthly from newly released genome sequences. Additional tools were
      created to allow the alignment of flanking sequences in search for similarities
      between different loci and to build dictionaries of unique sequences. To date,
      almost six hundred CRISPRs have been identified in 475 published genomes. Two
      Archeae out of thirty-seven and about half of Bacteria do not possess a CRISPR.
      Fine analysis of repeated sequences strongly supports the current view that new
      motifs are added at one end of the CRISPR adjacent to the putative promoter.
      CONCLUSION: It is hoped that availability of a public database, regularly updated
      and which can be queried on the web will help in further dissecting and
      understanding CRISPR structure and flanking sequences evolution. Subsequent
      analyses of the intra-species CRISPR polymorphism will be facilitated by
      CRISPRFinder and the dictionary creator. CRISPRdb is accessible at
      http://crispr.u-psud.fr/crispr.

PMID- 17521439
TI  - Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical
      neuroleptics: a serotonergic approach.
AB  - BACKGROUND: Schizophrenia is a common psychiatric disease affecting about 1% of
      population. One major problem in the treatment is finding the right the drug for
      the right patients. However, pharmacogenetic results in psychiatry can seldom be
      replicated. METHODS: We selected three candidate genes associated with
      serotonergic neurotransmission for the study: serotonin 2A (5-HT2A) receptor
      gene, tryptophan hydroxylase 1 (TPH1) gene, and G-protein beta-3 subunit (GNB3)
      gene. We recruited 94 schizophrenia patients representing extremes in treatment
      response to typical neuroleptics: 43 were good responders and 51 were poor
      responders. The control group consisted of 392 healthy blood donors. RESULTS: We
      do, in part, replicate the association between 5-HT2A T102C polymorphism and
      response to typical neuroleptics. In female patients, C/C genotype was
      significantly more common in non-responders than in responders [OR = 6.04 (95% Cl
      1.67-21.93), p = 0.005] or in the control population [OR = 4.16 (95% CI 1.46
      11.84), p = 0.005]. TPH1 A779C C/A genotype was inversely associated with good
      treatment response when compared with non-responders [OR = 0.59 (95% Cl 0.36
      0.98), p = 0.030] or with the controls [OR = 0.44 (95% CI 0.23-0.86, p = 0.016],
      and GNB3 C825T C/T genotype showed a trend-like positive association among the
      male patients with a good response compared with non-responders [OR = 3.48 (95%
      Cl 0.92-13.25), p = 0.061], and a clearer association when compared with the
      controls [OR = 4.95 (95% CI 1.56-15.70), p = 0.004]. CONCLUSION: More findings on
      the consequences of functional polymorphisms for the role of serotonin in the
      development of brain and serotonergic neurotransmission are needed before more
      detailed hypotheses regarding susceptibility and outcome in schizophrenia can be
      formulated. The present results may highlight some of the biological mechanisms
      in different courses of schizophrenia between men and women.

PMID- 17521440
TI  - Immune system changes during simulated planetary exploration on Devon Island,
      high arctic.
AB  - BACKGROUND: Dysregulation of the immune system has been shown to occur during
      spaceflight, although the detailed nature of the phenomenon and the clinical
      risks for exploration class missions have yet to be established. Also, the
      growing clinical significance of immune system evaluation combined with epidemic
      infectious disease rates in third world countries provides a strong rationale for
      the development of field-compatible clinical immunology techniques and equipment.
      In July 2002 NASA performed a comprehensive immune assessment on field team
      members participating in the Haughton-Mars Project (HMP) on Devon Island in the
      high Canadian Arctic. The purpose of the study was to evaluate the effect of
      mission-associated stressors on the human immune system. To perform the study,
      the development of techniques for processing immune samples in remote field
      locations was required. Ten HMP-2002 participants volunteered for the study. A
      field protocol was developed at NASA-JSC for performing sample collection, blood
      staining/processing for immunophenotype analysis, whole-blood mitogenic culture
      for functional assessments and cell-sample preservation on-location at Devon
      Island. Specific assays included peripheral leukocyte distribution;
      constitutively activated T cells, intracellular cytokine profiles, plasma
      cortisol and EBV viral antibody levels. Study timepoints were 30 days prior to
      mission start, mid-mission and 60 days after mission completion. RESULTS: The
      protocol developed for immune sample processing in remote field locations
      functioned properly. Samples were processed on Devon Island, and stabilized for
      subsequent analysis at the Johnson Space Center in Houston. The data indicated
      that some phenotype, immune function and stress hormone changes occurred in the
      HMP field participants that were largely distinct from pre-mission baseline and
      post-mission recovery data. These immune changes appear similar to those observed
      in astronauts following spaceflight. CONCLUSION: The immune system changes
      described during the HMP field deployment validate the use of the HMP as a ground
      based spaceflight/planetary exploration analog for some aspects of human
      physiology. The sample processing protocol developed for this study may have
      applications for immune studies in remote terrestrial field locations. Elements
      of this protocol could possibly be adapted for future in-flight immunology
      studies conducted during space missions.

PMID- 17521442
TI  - Correlating metabolic and anatomic responses of primary lung cancers to
      radiotherapy by combined F-18 FDG PET-CT imaging.
AB  - BACKGROUND: To correlate the metabolic changes with size changes for tumor
      response by concomitant PET-CT evaluation of lung cancers after radiotherapy.
      METHODS: 36 patients were studied pre- and post-radiotherapy with18FDG PET-CT
      scans at a median interval of 71 days. All of the patients were followed
      clinically and radiographically after a mean period of 342 days for assessment of
      local control or failure rates. Change in size (sum of maximum orthogonal
      diameters) was correlated with that of maximum standard uptake value (SUV) of the
      primary lung cancer before and after conventional radiotherapy. RESULTS: There
      was a significant reduction in both SUV and size of the primary cancer after
      radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity,
      specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the
      corresponding values using and CT (size criteria) were 67%, 50%, and 65%
      respectively. The metabolic change (SUV) was highly correlated with the change in
      size by a quadratic function. In addition, the mean percentage metabolic change
      was significantly larger than that of size change (62.3 +/- 32.7% vs 47.1 +/-
      26.1% respectively, p = 0.03) CONCLUSION: Correlating and incorporating metabolic
      change by PET into size change by concomitant CT is more sensitive in assessing
      therapeutic response than CT alone.

PMID- 17521443
TI  - Adverse events among high-risk participants in a home-based walking study: a
      descriptive study.
AB  - BACKGROUND: For high-risk individuals and their healthcare providers, finding the
      right balance between promoting physical activity and minimizing the risk of
      adverse events can be difficult. More information on the prevalence and influence
      of adverse events is needed to improve providers' ability to prescribe effective
      and safe exercise programs for their patients. METHODS: This study describes the
      type and severity of adverse events reported by participants with cardiovascular
      disease or at-risk for cardiovascular disease that occurred during an
      unsupervised, home-based walking study. This multi-site, randomized controlled
      trial tested the feasibility of a diet and lifestyle activity intervention over
      1.5 years. At month 13, 274 eligible participants (male veterans) were recruited
      who were ambulatory, BMI > 28, and reporting one or more cardiovascular disease
      risk factors. All participants attended five, face-to-face dietitian-delivered
      counseling sessions during the six-month intervention. Participants were
      randomized to three study arms: 1) time-based walking goals, 2) simple pedometer
      based walking goals, and 3) enhanced pedometer-based walking goals with Internet
      mediated feedback. Two physicians verified adverse event symptom coding. RESULTS:
      Enrolled participants had an average of five medical comorbidities. During 1110
      person months of observation, 87 of 274 participants reported 121 adverse events.
      One serious study-related adverse event (atrial fibrillation) was reported; the
      individual resumed study participation within three days. Non-serious, study
      related adverse events made up 12% of all symptoms - predominantly minor
      musculoskeletal events. Serious, non-study related adverse events represented 32%
      of all symptoms while non-serious, non-study related adverse events made up 56%
      of symptoms. Cardiovascular disease events represented over half of the non-study
      related adverse event symptoms followed by musculoskeletal complaints. Adverse
      events caused 50 temporary suspensions averaging 26 days in duration before
      physician medical clearance was obtained to resume walking. CONCLUSION: Men at
      high risk for adverse cardiovascular events can safely be advised to start a
      progressive walking program. Results suggest that minor to serious medical
      problems unrelated to exercise are a major barrier to walking adherence. Helping
      individuals with chronic illness return to physical activity quickly but safely
      after an adverse event is an important component of any physical activity
      intervention targeting this population.

PMID- 17521445
TI  - Genes encoding pentatricopeptide repeat (PPR) proteins are not conserved in
      location in plant genomes and may be subject to diversifying selection.
AB  - BACKGROUND: The pentatricopeptide repeat (PPR) is a degenerate 35 amino acid
      motif that occurs in multiple tandem copies in members of a recently recognized
      eukaryotic gene family. Most analyzed eukaryotic genomes contain only a small
      number of PPR genes, but in plants the family is greatly expanded. The factors
      that underlie the expansion of this gene family in plants are not as yet
      understood. RESULTS: We show that the location of PPR genes is highly variable in
      comparisons between orthologous, closely related, and otherwise co-linear
      chromosomal regions of the Brassica rapa or radish and Arabidopsis thaliana. This
      observation also pertains to paralogous duplicated segments of the genomes of
      Arabidopsis thaliana and Brassica rapa. In addition, we show that PPR genes that
      seem closely linearly aligned in these comparisons are not generally found to be
      closely related to one another at the nucleotide and amino acid sequence level.
      We observe a relatively high level of non-synonomous vs synonomous changes among
      a group tandemly repeated radish PPR genes, suggesting that these, and possibly
      other PPR genes, are subject to diversifying selection. We also show that a
      duplicated region of the Arabidopsis genome possesses a relatively high density
      of PPR genes showing high similarity to restorers of fertility of cytoplasmic
      male sterile (CMS) systems of petunia, radish and rice. The PPR genes in these
      regions, together with the restorer genes, are more highly similar to one
      another, in sequence as well as in structure, than to other PPR genes, even
      within the same sub-family. CONCLUSION: Our results suggest are consistent with a
      model in which at least some PPR genes undergo a "birth and death" process that
      involves transposition to unrelated chromosomal sites. PPR genes hold certain
      features in common with disease resistance genes (R genes), and their "nomadic"
      character suggests that their evolutionary expansion in plants may have involved
      novel molecular processes and selective pressures.

PMID- 17521444
TI  - Discovering functional linkages and uncharacterized cellular pathways using
      phylogenetic profile comparisons: a comprehensive assessment.
AB  - BACKGROUND: A widely-used approach for discovering functional and physical
      interactions among proteins involves phylogenetic profile comparisons (PPCs).
      Here, proteins with similar profiles are inferred to be functionally related
      under the assumption that proteins involved in the same metabolic pathway or
      cellular system are likely to have been co-inherited during evolution. RESULTS:
      Our experimentation with E. coli and yeast proteins with 16 different carefully
      composed reference sets of genomes revealed that the phyletic patterns of
      proteins in prokaryotes alone could be adequate enough to make reasonably
      accurate functional linkage predictions. A slight improvement in performance is
      observed on adding few eukaryotes into the reference set, but a noticeable drop
      off in performance is observed with increased number of eukaryotes. Inclusion of
      most parasitic, pathogenic or vertebrate genomes and multiple strains of the same
      species into the reference set do not necessarily contribute to an improved
      sensitivity or accuracy. Interestingly, we also found that evolutionary histories
      of individual pathways have a significant affect on the performance of the PPC
      approach with respect to a particular reference set. For example, to accurately
      predict functional links in carbohydrate or lipid metabolism, a reference set
      solely composed of prokaryotic (or bacterial) genomes performed among the best
      compared to one composed of genomes from all three super-kingdoms; this is in
      contrast to predicting functional links in translation for which a reference set
      composed of prokaryotic (or bacterial) genomes performed the worst. We also
      demonstrate that the widely used random null model to quantify the statistical
      significance of profile similarity is incomplete, which could result in an
      increased number of false-positives. CONCLUSION: Contrary to previous proposals,
      it is not merely the number of genomes but a careful selection of informative
      genomes in the reference set that influences the prediction accuracy of the PPC
      approach. We note that the predictive power of the PPC approach, especially in
      eukaryotes, is heavily influenced by the primary endosymbiosis and subsequent
      bacterial contributions. The over-representation of parasitic unicellular
      eukaryotes and vertebrates additionally make eukaryotes less useful in the
      reference sets. Reference sets composed of highly non-redundant set of genomes
      from all three super-kingdoms fare better with pathways showing considerable
      vertical inheritance and strong conservation (e.g. translation apparatus), while
      reference sets solely composed of prokaryotic genomes fare better for more
      variable pathways like carbohydrate metabolism. Differential performance of the
      PPC approach on various pathways, and a weak positive correlation between
      functional and profile similarities suggest that caution should be exercised
      while interpreting functional linkages inferred from genome-wide large-scale
      profile comparisons using a single reference set.

PMID- 17521446
TI  - Expression of nitric oxide synthase isoforms in the dorsal horn of monoarthritic
      rats: effects of competitive and uncompetitive N-methyl-D-aspartate antagonists.
AB  - Chronic pain is associated with N-methyl-D-aspartate (NMDA) receptor activation
      and downstream production of nitric oxide, which has a pivotal role in
      multisynaptic local circuit nociceptive processing in the spinal cord. The
      formation of nitric oxide is catalyzed by three major nitric oxide synthase (NOS)
      isoforms (neuronal, nNOS; inducible, iNOS; endothelial, eNOS), which are
      increased in the spinal cord of rodents subjected to some tonic and chronic forms
      of experimental pain. Despite the important role of NOS in spinal cord
      nociceptive transmission, there have been no studies exploring the effect of NMDA
      receptor blockade on NOS expression in the dorsal horn during chronic pain.
      Furthermore, NOS isoforms have not been fully characterized in the dorsal horn of
      animals subjected to arthritic pain. The aim of this work was therefore to study
      the expression of nNOS, iNOS and eNOS in the dorsal horns of monoarthritic rats,
      and the modifications in NOS expression induced by pharmacological blockade of
      spinal cord NMDA receptors. Monoarthritis was produced by intra-articular
      injection of complete Freund's adjuvant into the right tibio-tarsal joint. At
      week 4, monoarthritic rats were given either the competitive NMDA antagonist (+/
      )-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) or the uncompetitive
      NMDA antagonist ketamine. After 6 and 24 hours, animals were killed and posterior
      quadrants of the lumbar spinal cord were dissected. Sample tissues were
      homogenized and subjected to immunoblotting with anti-nNOS, anti-iNOS or anti
      eNOS monoclonal antibodies. The nNOS isoform, but not the iNOS and eNOS isoforms,
      were detected in the dorsal horns of control rats. Monoarthritis increased the
      expression of nNOS, iNOS and eNOS in the dorsal horns ipsilateral and
      contralateral to the inflamed hindpaw. Intrathecal administration of CPP and
      ketamine reduced nNOS expression in monoarthritic rats but increased the
      expression of iNOS and eNOS. Results suggest that blockade of spinal cord NMDA
      receptors produces complex regulatory changes in the expression of NOS isoforms
      in monoarthritic rats that may be relevant for nitridergic neuronal/glial
      mechanisms involved in the pathophysiology of monoarthritis and in the
      pharmacological response to drugs interacting with NMDA receptors.

PMID- 17521447
TI  - Inhibition of hydrogen uptake in Escherichia coli by expressing the hydrogenase
      from the cyanobacterium Synechocystis sp. PCC 6803.
AB  - BACKGROUND: Molecular hydrogen is an environmentally-clean fuel and the
      reversible (bi-directional) hydrogenase of the cyanobacterium Synechocystis sp.
      PCC 6803 as well as the native Escherichia coli hydrogenase 3 hold great promise
      for hydrogen generation. These enzymes perform the simple reaction 2H+ + 2e- <-->
      H2 (g). RESULTS: Hydrogen yields were enhanced up to 41-fold by cloning the
      bidirectional hydrogenase (encoded by hoxEFUYH) from the cyanobacterium into E.
      coli. Using an optimized medium, E. coli cells expressing hoxEFUYH also produced
      twice as much hydrogen as the well-studied Enterobacter aerogenes HU-101, and
      hydrogen gas bubbles are clearly visible from the cultures. Overexpression of
      HoxU alone (small diaphorase subunit) accounts for 43% of the additional hydrogen
      produced by HoxEFUYH. In addition, hydrogen production in E. coli mutants with
      defects in the native formate hydrogenlyase system show that the cyanobacterial
      hydrogenase depends on both the native E. coli hydrogenase 3 as well as on its
      maturation proteins. Hydrogen absorption by cells expressing hoxEFUYH was up to
      10 times lower than cells which lack the cloned cyanobacterial hydrogenase;
      hence, the enhanced hydrogen production in the presence of hoxEFUYH is due to
      inhibition of hydrogen uptake activity in E. coli. Hydrogen uptake by cells
      expressing hoxEFUYH was suppressed in three wild-type strains and in two hycE
      mutants but not in a double mutant defective in hydrogenase 1 and hydrogenase 2;
      hence, the active cyanobacterial locus suppresses hydrogen uptake by hydrogenase
      1 and hydrogenase 2 but not by hydrogenase 3. Differential gene expression
      indicated that overexpression of HoxEFUYH does not alter expression of the native
      E. coli hydrogenase system; instead, biofilm-related genes are differentially
      regulated by expression of the cyanobacterial enzymes which resulted in 2-fold
      elevated biofilm formation. This appears to be the first enhanced hydrogen
      production by cloning a cyanobacterial enzyme into a heterologous host.
      CONCLUSION: Enhanced hydrogen production in E. coli cells expressing the
      cyanobacterial HoxEFUYH is by inhibiting hydrogen uptake of both hydrogenase 1
      and hydrogenase 2.

PMID- 17521448
TI  - An ecological study of regional variation in work injuries among young workers.
AB  - BACKGROUND: The investigation of geographic variation in occupational injuries
      has received little attention. Young workers 15 to 24 years are of particular
      concern because they consistently show elevated occupational injury rates
      compared to older workers. The present study sought to: (a) to describe the
      geographic variation of work injuries; (b) to determine whether geographic
      variation remained after controlling for relevant demographic and job
      characteristics; (c) to identify the region-level factors that correlate with the
      geographic variation. METHODS: Using workers compensation claims and census data,
      we estimated claim rates per 100 full-time equivalents for 15 to 24 year olds in
      46 regions in Ontario. A total of 21 region-level indicators were derived
      primarily from Census and Labour Force Survey data to reflect social and material
      deprivation of the region as well as demographic and employment characteristics
      of youth living in those areas. RESULTS: Descriptive findings showed substantial
      geographic variation in young worker injury rates, even after controlling for
      several job and demographic variables. Region-level characteristics such as
      greater residential stability were associated with low work injury rates. Also,
      regions with the lowest claim rates tended to have proportionally fewer cuts and
      burns than high-claim-rate regions. CONCLUSION: The finding of substantial
      geographic variation in youth claim rates even after controlling for demographic
      and job factors can aid in targeting prevention resource. The association between
      region-level indicators such as residential stability and youth work injury
      suggests that work injury prevention strategies can be integrated with other
      local economic development measures. The findings partially support the notion
      that work safety measures may be unevenly distributed with respect to regional
      socio-economic factors.

PMID- 17521449
TI  - Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador:
      potential for elimination of infection.
AB  - BACKGROUND: Onchocerciasis is a leading cause of blindness worldwide, hence
      elimination of the infection is an important health priority. Community-based
      treatment programs with ivermectin form the basis of control programs for the
      disease in Latin America. The long-term administration of ivermectin could
      eliminate Onchocerca volvulus infection from endemic areas in Latin America.
      METHODS: A strategy of annual to twice-annual treatments with ivermectin has been
      used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The
      impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and
      transmission was monitored in seven sentinel communities. RESULTS: Over the
      period 1990-2003, high rates of treatment coverage of the eligible population
      were maintained in endemic communities (mean 85.2% per treatment round).
      Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in
      sentinel communities and had a major impact on the prevalence and transmission of
      infection, with possible elimination of infection in some foci. CONCLUSION: The
      distribution of ivermectin in endemic communities in Ecuador might have
      eliminated ocular morbidity and significant progress has been made towards
      elimination of the infection. A strategy of more frequent treatments with
      ivermectin may be required in communities where the infection persists to achieve
      the objective of elimination of the infection from Ecuador. The elimination of
      the infection from an endemic country in Latin America would be a major public
      health achievement and could stimulate the implementation of elimination
      strategies in other endemic countries.

PMID- 17521450
TI  - Regeneration of neural crest derivatives in the Xenopus tadpole tail.
AB  - BACKGROUND: After amputation of the Xenopus tadpole tail, a functionally
      competent new tail is regenerated. It contains spinal cord, notochord and muscle,
      each of which has previously been shown to derive from the corresponding tissue
      in the stump. The regeneration of the neural crest derivatives has not previously
      been examined and is described in this paper. RESULTS: Labelling of the spinal
      cord by electroporation, or by orthotopic grafting of transgenic tissue
      expressing GFP, shows that no cells emigrate from the spinal cord in the course
      of regeneration. There is very limited regeneration of the spinal ganglia, but
      new neurons as well as fibre tracts do appear in the regenerated spinal cord and
      the regenerated tail also contains abundant peripheral innervation.The
      regenerated tail contains a normal density of melanophores. Cell labelling
      experiments show that melanophores do not arise from the spinal cord during
      regeneration, nor from the mesenchymal tissues of the skin, but they do arise by
      activation and proliferation of pre-existing melanophore precursors. If tails are
      prepared lacking melanophores, then the regenerates also lack them. CONCLUSION:
      On regeneration there is no induction of a new neural crest similar to that seen
      in embryonic development. However there is some regeneration of neural crest
      derivatives. Abundant melanophores are regenerated from unpigmented precursors,
      and, although spinal ganglia are not regenerated, sufficient sensory systems are
      produced to enable essential functions to continue.

PMID- 17521451
TI  - The possible role of cell cycle regulators in multistep process of HPV-associated
      cervical carcinoma.
AB  - BACKGROUND: Human papillomavirus (HPV) 16 and 18 are associated with cervical
      carcinogenesis through an interaction between HPV oncogenic proteins and cell
      cycle regulatory genes. However, the exact pathogenetic mechanisms are not
      determined yet. METHODS: We investigated 43 invasive squamous cell carcinoma
      (ISCC), 38 CIN III, 11 CINII and 18 CINI for cyclin D1, cyclin E, CDK4, p53, mdm
      2, p21(waf), p27, p16(INK4A), Rb and Ki-67 aberrations using immunohistochemistry
      and molecular techniques. Twenty samples of normal cervical tissues (NCT) were
      taken as a control. RESULTS: There was a significant increase in the expression
      of Ki-67, cyclin E, CDK4, p16(INK4A), Rb (p= 0.003, 0.001, 0.001, 0.01) and a
      significant decrease in p27(KIP1) from NCT to ISCC (p = 0.003). Increased cyclin
      D1, p21(waf), p53, mdm-2 expression, homozygous deletion (HZD) and promoter
      methylation (PM) of the Rb were detected in CINIII and ISCC only. On univariate
      analysis; tumor size, differentiation, lymph node status, FIGO stage, Ki-67,
      cyclin D1, p53 and p27(KIP1) are significantly associated with reduced overall
      survival (OS) while on multivariate analysis; only FIGO stage, Ki-67, cyclin D1,
      p53 and p27(KIP1) were significant. CONCLUSION: 1) Aberrations involving
      p27(KIP1), cyclin E, CDK4, p16(INK4A) are considered early events in HPV 16 and
      18-associated cervical carcinoma, whereas cyclin D1 and p53 pathway abnormalities
      are considered late events. 2) Immunohistochemical tests for p16(INK4A) and
      cyclin E, could help in early diagnosis of cervical carcinoma. 3) Only FIGO stage
      p53, cyclin D1, p27(KIP1) and Ki-67 are independent prognostic factors that might
      help in predicting outcome of cervical cancer patients.

PMID- 17521452
TI  - Glycolysis and the regulation of glucose transport in Lactococcus lactis spp.
      lactis in batch and fed-batch culture.
AB  - BACKGROUND: Despite the fact that many reports deal with glycolysis in
      Lactococcus lactis, there is not much information on the regulation of uptake of
      glucose itself. The aim of the present work was to investigate the effect of the
      glucose level on its specific uptake rate. RESULTS: Studies on aeration levels in
      pH controlled L. lactis spp. lactis batch cultures on glucose (55 mM) showed that
      product formation is extremely homolactic and the highest yield of lactate on
      glucose is obtained under microaerobic conditions (5% dissolved oxygen).
      Microaerobic conditions were therefore applied in experiments carried out to
      investigate the regulation of the uptake of glucose. The tool of glucostat fed
      batch culture was employed, in which glucose was added at a rate suitable to
      maintain a stable concentration throughout the runs with glucose concentration
      ranging from 13.75 to 555 mM. The glucostat experiments showed that the
      concentration of glucose influences its specific uptake rate and consequently the
      glycolytic flux, as well as the fermentation pattern. The highest specific
      activities of the key glycolytic enzymes PFK, PYK and the LDH were obtained at 55
      mM glucose, the area of the highest observed glycolytic flux. Reduction of the
      glycolytic flux by 55% in the 277 mM glucostat corresponded to an almost
      identical reduction in PFK activity, indicating a certain controlling influence
      of this enzyme on the flux, through the glucose effect. CONCLUSION: Determination
      of intracellular metabolites' pools showed that FBP cannot be regarded as a
      direct regulator of product formation, since almost identical concentrations were
      obtained at both low (13.75 mM) and high (138 mM) glucose levels, at which
      neither the glucose uptake rates and the glycolytic flux, nor the fermentation
      patterns were similar (mixed acids vs homolactic, respectively). Glucostat data
      showed instead that the control of the flux through the glycolytic pathway under
      the examined conditions, resides to a large extent in processes outside the
      pathway, like the ATP consuming reactions and glucose transport. A regulation
      mechanism is proposed governed by the energy state of the cell by which L. lactis
      can handle the glycolytic flux through the allosteric properties of key enzymes,
      with PFK having a significant influence on the control.

PMID- 17521453
TI  - Mouse maps of gene expression in the brain.
AB  - The completion of the Allen Brain Atlas generated a great deal of press interest
      and enthusiasm from the research community. What does it do, and what other
      complementary resources increase its functionality?

PMID- 17521454
TI  - Pulse pressure variation: beyond the fluid management of patients with shock.
AB  - In anesthetized patients without cardiac arrhythmia the arterial pulse pressure
      variation (PPV) induced by mechanical ventilation has been shown the most
      accurate predictor of fluid responsiveness. In this respect, PPV has so far been
      used mainly in the decision-making process regarding volume expansion in patients
      with shock. As an indicator of the position on the Frank-Starling curve, PPV may
      actually be useful in many other clinical situations. In patients with acute lung
      injury or with acute respiratory distress syndrome, PPV can predict hemodynamic
      instability induced by positive end-expiratory pressure and recruitment
      maneuvers. PPV may also be useful to prevent excessive fluid
      restriction/depletion in patients with pulmonary edema, and to prevent excessive
      ultrafiltration in critically ill patients undergoing hemodialysis or
      hemofiltration. In the operating room, a goal-directed fluid therapy based on PPV
      monitoring has the potential to improve the outcome of patients undergoing high
      risk surgery.

PMID- 17521455
TI  - Steroids in early ARDS?

PMID- 17521456
TI  - Clinical review: agitation and delirium in the critically ill--significance and
      management.
AB  - Agitation is a psychomotor disturbance characterized by a marked increase in
      motor and psychological activity in a patient. It occurs very frequently in the
      intensive care setting. It may be isolated, or accompanied by other mental
      disorders, such as severe anxiety and delirium. Frequently, agitation is a sign
      of brain dysfunction and, as such, may have adverse consequences, for at least
      two reasons. First, agitation can interfere with the patient's care and second,
      there is evidence demonstrating that the prognosis of agitated (and delirious)
      patients is worse than that of non-agitated (non-delirious) patients. These
      conditions are often under-diagnosed in the intensive care unit (ICU).
      Consequently, a systematic evaluation of this problem in ICU patients should be
      conducted. Excellent tools are presently available for this purpose. Treatment,
      including prevention, must be undertaken without delay, and the ICU physician
      should follow logical, strict and systematic rules when applying therapy.

PMID- 17521457
TI  - Evaluating dosage compensation as a cause of duplicate gene retention in
      Paramecium tetraurelia.
AB  - The high retention of duplicate genes in the genome of Paramecium tetraurelia has
      led to the hypothesis that most of the retained genes have persisted because of
      constraints due to gene dosage. This and other possible mechanisms are discussed
      in the light of expectations from population genetics and systems biology.

PMID- 17521458
TI  - The fungal frontier.
AB  - A report of the 24th Fungal Genetics Conference, Asilomar, USA, 20-25 March 2007.

PMID- 17521459
TI  - Hospital at home: the right place for the right patient.

PMID- 17521460
TI  - Home treatment of infection-related acute respiratory failure in kyphoscoliotic
      patients on long-term mechanical ventilation.
AB  - BACKGROUND: In patients with kyphoscoliosis, long-term mechanical ventilation
      improves chronic alveolar hypoventilation during spontaneous breathing, improves
      quality of life, decreases the need for hospitalization, and improves survival.
      In these patients respiratory infection can precipitate acute respiratory failure
      (ARF) that requires hospitalization. OBJECTIVE: To study the possibility of home
      treatment of infection-related ARF in kyphoscoliotic patients on long-term
      mechanical ventilation. METHODS: During a period of 4 years, 8 kyphoscoliotic
      patients (3 women, 5 men, mean +/- SD age 61 +/- 10 y, mean Cobb angle 84 +/- 7
      degrees ), who had been using overnight mechanical ventilation (delivered by
      either volume-limited [4] or pressure-limited [4] ventilators) for 31 +/- 32
      months, developed infection-related ARF. Seven patients agreed to be treated at
      home, with an increase of the daily duration of mechanical ventilation to > 20
      hours, and antibiotics. Blood oxygen saturation was monitored via pulse oximetry
      during mechanical ventilation and overnight, to determine whether to add or
      increase supplemental oxygen. A nurse, a general practitioner, and a chest
      specialist made scheduled visits to each patient. RESULTS: All 7 patients were
      successfully treated at home. In 2 patients supplemental oxygen flow was slightly
      increased. Two patients who had not previously been receiving supplemental oxygen
      received supplemental oxygen for a few days. The patients progressively decreased
      the daily duration of mechanical ventilation, according to their ability to
      breathe comfortably without mechanical assistance, under the supervision of the
      medical staff, and they all returned to their baseline (pre-ARF) condition in 4
      weeks. CONCLUSION: In kyphoscoliotic patients on long-term mechanical
      ventilation, home treatment of infection-related ARF is possible and effective,
      provided there is adequate collaboration by the patients and their relatives, and
      staff well-trained in mechanical ventilation and other aspects of the home care
      of these patients.

PMID- 17521461
TI  - The effect of lung resection on pulmonary function and exercise capacity in lung
      cancer patients.
AB  - OBJECTIVE: Prospectively to evaluate the effects of lung resection on lung
      function (as measured via spirometry) and exercise capacity (as measured via
      shuttle-walk test) in lung cancer patients. METHODS: We conducted pulmonary
      function tests and the shuttle-walk test with 110 consecutive patients, before
      and 1 month, 3 months, and 6 months after lobectomy (n = 73) or pneumonectomy (n
      = 37). All the patients underwent a standard posterolateral thoracotomy. Eighty
      eight patients completed all 3 postoperative assessments. RESULTS: At 6 months
      after resection, the lobectomy patients had lost 15% of their preoperative forced
      expiratory volume in the first second (FEV1) (p < 0.001) and 16% of their
      exercise capacity (p < 0.001), and the pneumonectomy patients had lost 35% of
      their preoperative FEV(1) (p < 0.001) and 23% of their exercise capacity (p <
      0.001). CONCLUSIONS: Lobectomy patients suffered significant reduction of
      functional reserve, with almost equal deterioration between lung function and
      exercise capacity. Pneumonectomy patients had a more substantial loss of
      functional reserve, and a disproportionate loss of pulmonary function relative to
      exercise capacity. Therefore, pulmonary function test values considered in
      isolation may exaggerate the loss of functional exercise capacity in
      pneumonectomy patients, which is important because many lung cancer patients who
      require resection for cure are prepared to accept the risks of immediate surgical
      complications and mortality, but are unwilling to risk long-term poor exercise
      capacity.

PMID- 17521462
TI  - The ear as an alternative site for a pulse oximeter finger clip sensor.
AB  - BACKGROUND: Finger clip pulse oximetry sensors are commonly used to obtain
      functional oxygen saturation readings (S(pO2)), but these sensors may perform
      poorly if the digit is poorly perfused or there is excessive hand movement. I
      have increasingly witnessed clinicians obtaining S(pO2) readings by placing the
      finger clip sensor on the patient's ear when an S(pO2) reading cannot be obtained
      from a finger. OBJECTIVE: Determine if reliable S(pO2) readings can be obtained
      from a finger clip sensor placed on the ear. METHODS: This was a prospective
      study with patients undergoing pulmonary function testing. The calculated
      functional oxygen saturation values from arterial blood gas analysis (S(aO2))
      were compared with S(pO2) readings from a finger clip sensor placed on a finger
      (finger S(pO2)) and on the upper portion of an ear (ear S(pO2)). S(pO2) data were
      included in the study only if (1) the pulse rate from finger S(pO2) and ear
      S(pO2) differed by < or = 5 beats/min and (2) the photoplethysmographic waveform
      was stable and acceptable. RESULTS: Data were obtained from 30 adult white
      patients. The number of S(pO2) readings that differed from the S(aO2) values by >
      or = 3% were 1 (3.3%) finger S(pO2) reading and 24 (80%, 95% CI 61%-92%) ear
      S(pO2) readings (p < or = 0.001). Bland-Altman analysis showed better agreement
      between S(aO2) and finger S(pO2) (mean +/- 2 SD limits of agreement -2.35 to
      2.35) than between S(aO2) and ear S(pO2) (limits of agreement -7.24 to -0.08) or
      finger S(pO2) and ear S(pO2) (limits of agreement -7.56 to -0.23). CONCLUSION: A
      pulse oximeter finger clip sensor placed on the ear does not provide clinically
      reliable S(pO2) readings.

PMID- 17521463
TI  - Management and processing of respiratory care information in respiratory care
      departments.
AB  - BACKGROUND: Though much research has been done to determine best practice and to
      examine the role of evidence-based guidelines and respiratory therapist (RT)
      driven protocols in enhancing patient care and reducing health care costs, very
      little attention has been paid to how respiratory care information is managed and
      processed. OBJECTIVE: To examine information systems currently used in
      respiratory care departments to determine if they are effective and efficient in
      managing and processing respiratory care information. METHODS: To 50 RTs at 16
      respiratory therapy departments in New York, Houston, and Miami, we distributed
      questionnaires designed to determine the strengths, weaknesses, and usefulness of
      existing respiratory care information systems. There were 2 types of
      questionnaire: one for respiratory care managers and another for staff RTs. We
      used a combination of purposive and snowball sampling techniques to choose RTs to
      whom to send the survey. RESULTS: The response rate was 52%. Of the 26
      respondents, 19 were staff RTs and 7 were managers. In the 16 departments that
      responded, 3 of the information systems were strictly paper-based, 12 were
      partially automated (combination of paper records and computer files), and 1 was
      fully automated. The respondents' opinions about the usefulness of their
      information systems were: 19% said "very useful," 23% said "useful," 46% said
      "somewhat useful," and 12% said "not useful." All the respondents said that they
      rely on colleagues, books, and manuals for decision support, rather than on
      computerized decision-support systems. CONCLUSIONS: This study suggests that the
      information systems used by the respondent RTs have marginal utility and have
      problems with data storage and retrieval, because either the systems do not
      employ computerized databases or the computerized databases do not have full
      scale database management systems. Inadequate data storage and retrieval systems
      often lead to data redundancy and, ultimately, inaccurate information.
      Development of data models specific to the respiratory care profession may be
      necessary to build databases with conceptual schemas that accurately reflect the
      professional activities of RTs.

PMID- 17521464
TI  - Performance comparison of 15 transport ventilators.
AB  - BACKGROUND: Numerous mechanical ventilators are designed and marketed for use in
      patient transport. The complexity of these ventilators differs considerably, but
      very few data exist to compare their operational capabilities. METHODS: Using
      bench and animal models, we studied 15 currently available transport ventilators
      with regard to their physical characteristics, gas consumption (duration of an E
      size oxygen cylinder), battery life, ease of use, need for compressed gas,
      ability to deliver set ventilation parameters to a test lung under 3 test
      conditions, and ability to maintain ventilation and oxygenation in normal and
      lung-injured sheep. RESULTS: Most of the ventilators tested were relatively
      simple to operate and had clearly marked controls. Oxygen cylinder duration
      ranged from 30 min to 77 min. Battery life ranged from 70 min to 8 hours. All
      except 3 of the ventilators were capable of providing various F(IO2) values. Ten
      of the ventilators had high-pressure and patient-disconnect alarms. Only 6 of the
      ventilators were able to deliver all settings as specifically set on the
      ventilator during the bench evaluation. Only 4 of the ventilators were capable of
      maintaining ventilation, oxygenation, and hemodynamics in both the normal and the
      lung-injured sheep. CONCLUSIONS: Only 2 of the ventilators met all the trial
      targets in all the bench and animal tests. With many of the ventilators, certain
      of the set ventilation parameters were inaccurate (differed by > 10% from the
      values from a cardiopulmonary monitor). The physical characteristics and high gas
      consumption of some of these ventilators may render them less desirable for
      patient transport.

PMID- 17521465
TI  - Respiratory failure due to expiratory central airway collapse.
AB  - We report a patient with respiratory failure due to expiratory central airway
      collapse successfully treated with airway stents. A 74-year-old male with obesity
      and obstructive sleep apnea had recurrent episodes of acute respiratory failure.
      Noninvasive positive-pressure ventilation failed because of patient intolerance
      and lack of improvement, and soon after he stopped using the noninvasive
      ventilator he developed severe respiratory failure that required a tracheostomy.
      He was transferred to our institution one month later. Fiberoptic bronchoscopy
      revealed diffuse expiratory central airway collapse of both main bronchi and the
      lower two thirds of the trachea, caused by bulging of the posterior airway
      membrane. During rigid bronchoscopy we inserted studded silicone stents in the
      right and left mainstem bronchi and in the distal trachea. The patient was weaned
      from mechanical ventilation 72 hours later and discharged to a long-term care
      facility. Expiratory central airway collapse should be considered in the
      differential diagnosis of patients with respiratory failure, especially when
      weaning from mechanical ventilation is difficult.

PMID- 17521466
TI  - Bronchus-associated lymphoid tissue lymphoma and Mycobacterium tuberculosis
      infection: an unusual case and a review of the literature.
AB  - Bronchus-associated lymphoid tissue lymphoma is a rare disease. It is the most
      common form of primary pulmonary lymphoma but accounts for less than 1% of all
      non-Hodgkin's lymphomas. We describe a 67-year-old man who, despite successful
      treatment of active miliary tuberculosis, developed progression of a concomitant
      bronchus-associated lymphoid tissue lymphoma. This case is in contrast to
      previous reports of gastrointestinal-mucosa-associated lymphoid tissue lymphomas
      and bronchus-associated lymphoid tissue lymphomas, in which treatment of the
      precipitating antigenic stimulus lead to remission of the lymphoma.

PMID- 17521467
TI  - A positive methacholine challenge test in the absence of symptoms.

PMID- 17521468
TI  - Validation of a food frequency questionnaire to assess folate intake of Dutch
      elderly people.
AB  - Folate is required for 1-carbon metabolism and deficiency in folate leads to
      megaloblastic anemia. Low levels of folate have been associated with increased
      risk of vascular disease. To investigate whether RDA of folate are met, habitual
      folate intake needs to be assessed reliably. We developed a FFQ to specifically
      measure folate intake over the previous 3 months in elderly people in the
      Netherlands. Major sources of folate intake, i.e. foods contributing to at least
      80% of the average folate intake, were identified through an analysis of the
      second Dutch Food Consumption Survey for the sub-population of men and women aged
      50-70. In 2000 and 2001, folate intake was estimated with this questionnaire in
      1286 individuals aged 50-75 years. Concentrations of serum and erythrocyte folate
      served as biomarkers with which relative validity of the questionnaire was
      assessed. The same FFQ was repeated after 3 years in 803 subjects in order to
      assess long-term reproducibility. Mean folate intake was estimated to be 196 (SD
      69) microg/d. Spearman correlation coefficients between folate intake and serum
      and erythrocyte concentrations were 0.14 (P < 0.01) and 0.05 (P = 0.06)
      respectively. Spearman correlations between folate intakes measured at baseline
      and after 3 years were 0.58 (P < 0.01). 47% of the participants were classified
      in the same quartiles on the two occasions. Our FFQ showed a weak correlation
      between folate intake and blood folate concentrations and reproducibility was
      acceptable. This FFQ is able to rank subjects according to their folate intake.

PMID- 17521469
TI  - Microbial and dietary factors associated with the 8-prenylnaringenin producer
      phenotype: a dietary intervention trial with fifty healthy post-menopausal
      Caucasian women.
AB  - Hop-derived food supplements and beers contain the prenylflavonoids xanthohumol
      (X), isoxanthohumol (IX) and the very potent phyto-oestrogen (plant-derived
      oestrogen mimic) 8-prenylnaringenin (8-PN). The weakly oestrogenic IX can be
      bioactivated via O-demethylation to 8-PN. Since IX usually predominates over 8
      PN, human subjects may be exposed to increased doses of 8-PN. A dietary
      intervention trial with fifty healthy post-menopausal Caucasian women was
      undertaken. After a 4 d washout period, participants delivered faeces, blank
      urine and breath samples. Next, they started a 5 d treatment with hop-based
      supplements that were administered three times per d and on the last day, a 24 h
      urine sample was collected. A semi-quantitative FFQ was used to estimate fat,
      fibre, alcohol, caffeine and theobromine intakes. The recoveries of IX, 8-PN and
      X in the urine were low and considerable inter-individual variations were
      observed. A five-fold increase in the dosage of IX without change in 8-PN
      concentration resulted in a significant lower IX recovery and a higher 8-PN
      recovery. Classification of the subjects into poor (60%), moderate (25%) and
      strong (15%) 8-PN producers based on either urinary excretion or microbial
      bioactivation capacity gave comparable results. Recent antibiotic therapy seemed
      to affect the 8-PN production negatively. A positive trend between methane
      excretion and 8-PN production was observed. Strong 8-PN producers consumed less
      alcohol and had a higher theobromine intake. From this study we conclude that in
      vivo O-demethylation of IX increases the oestrogenic potency of hop-derived
      products.

PMID- 17521470
TI  - Relationships between acceptance of sour taste and fruit intakes in 18-month-old
      infants.
AB  - The present study examined whether infants show an acceptance for extreme sour
      tastes and whether acceptance of sour taste is related to infants' fruit intake.
      Fruit intake of fifty-three infants at 6, 12 and 18 months was assessed using 3 d
      food records. Sour acceptance of these infants was studied at 18.1 (SD 1.5)
      months. Acceptance for four solutions differing in citric acid concentrations
      (0.00 M, 0.013 M, 0.029 M and 0.065 M) was measured by allowing infants ad
      libitum ingestion of each solution over brief time periods. The base solution to
      which citric acid was added was blackcurrant squash diluted in water. Infants'
      relative intake of each solution was used as a measure of sour acceptance. At 18
      months, twelve infants readily accepted the two highest citric acid
      concentrations, whereas the remaining infants rejected these. Infants who
      accepted the most sour solutions had a significantly higher fruit intake (P =
      0.025) and a higher fruit variety (P = 0.015) at 18 months than the infants who
      rejected the highly sour taste. Furthermore, infants who accepted the most sour
      solutions consumed fruits more frequently at 18 months (chi2 5.1; P = 0.024).
      Infants who accepted the sourest solutions also had a higher fruit intake at 6
      months, and a significantly higher increase in their fruit intake from 12 to 18
      months. This is the first scientific study that demonstrates the acceptance of
      sour tastes in some infants at the age of 18 months. Furthermore, the present
      results suggest a relationship between acceptance of sour tastes and infants'
      fruit intakes.

PMID- 17521471
TI  - Awareness of disease in Alzheimer's dementia: description of a mild to moderate
      sample of patient and caregiver dyads in Brazil.
AB  - BACKGROUND: Impairment of deficit awareness is a clinically relevant feature of
      dementia affecting the maintenance of decision capacities, management and safety
      of patients with risk behaviors, and caregiver burden. This study assessed
      awareness of disease of patient/caregiver dyads and the relationship between
      unawareness on various domains and sociodemographic variables among elderly
      Brazilians with Alzheimer's disease (AD). METHODS: The dyads (n=52), stratified
      by clinical severity and age groups, responded to the Assessment Scale of
      Psychosocial Impact of the Diagnosis of Dementia (ASPIDD). Statistical tests were
      used to compare clinical and sociodemographic variables and to calculate
      differences in rates of discrepant responses among mild and moderate dyads and
      between age groups, rates of discrepant responses among the ASPIDD domains, and
      association between awareness and age/age at onset. RESULTS: Awareness of
      deficits did not differ significantly among mild patients, whereas moderate
      patients showed impaired recognition on all domains. Older moderate dyads showed
      more discrepant responses, as compared to younger dyads at both severity stages.
      Mild patients could associate the disease with the cognitive deficits and
      recognized impairments on other domains. There was no significant relation of
      awareness with age at onset. CONCLUSION: Mild AD patients could associate the
      disease process with the presence of cognitive deficits, and also the changes in
      the emotional response with difficulties in social, family, and affective
      relations. Moderate AD patients were less aware of the symptoms and did not
      attribute them to the disease.

PMID- 17521472
TI  - Selection responses of means and inbreeding depression for female fecundity in
      Drosophila melanogaster suggest contributions from intermediate-frequency alleles
      to quantitative trait variation.
AB  - The extent to which quantitative trait variability is caused by rare alleles
      maintained by mutation, versus intermediate-frequency alleles maintained by
      balancing selection, is an unsolved problem of evolutionary genetics. We describe
      the results of an experiment to examine the effects of selection on the mean and
      extent of inbreeding depression for early female fecundity in Drosophila
      melanogaster. Theory predicts that rare, partially recessive deleterious alleles
      should cause a much larger change in the effect of inbreeding than in the mean of
      the outbred population, with the change in inbreeding effect having an opposite
      sign to the change in mean. The present experiment fails to support this
      prediction, suggesting that intermediate-frequency alleles contribute
      substantially to genetic variation in early fecundity.

PMID- 17521473
TI  - Pilot comparison between potassium titanyl phosphate laser and bipolar
      radiofrequency in paediatric tonsillectomy.
AB  - OBJECTIVES: To compare the advantages and disadvantages of potassium titanyl
      phosphate laser with those of bipolar radiofrequency techniques, in paediatric
      tonsillectomy. STUDY DESIGN: Prospective, randomised, clinical study. PATIENTS
      AND METHODS: From July 2004 to April 2006, 80 patients aged between 10 and 15
      years, with tonsillectomy planned for chronic tonsillitis, were included in the
      study. Children were prospectively randomised into two equal groups: potassium
      titanyl phosphate laser tonsillectomy and bipolar radiofrequency tonsillectomy.
      Operative time and intra-operative blood loss were recorded. Patients were
      scheduled for follow up during the first, second and fourth post-operative weeks.
      They were asked to record their pain and discomfort on a standardised visual
      analogue scale, from zero (no pain) to 10 (severe pain). Post-operative
      complications were also recorded and managed. RESULTS: The potassium titanyl
      phosphate laser group showed a slightly longer operative time (mean 12 minutes)
      than the bipolar radiofrequency group (mean 10 minutes). Intra-operative blood
      loss was significantly less in the potassium titanyl phosphate laser group (mean
      21 cm3) than in the bipolar radiofrequency group (mean 30 cm3). In the first
      week, post-operative pain scores were less in the potassium titanyl phosphate
      laser group than in the bipolar radiofrequency group (means 7.5 and 8.5,
      respectively). However, in the second week pain scores increased more in the
      potassium titanyl phosphate laser group than in the bipolar radiofrequency group
      (means 8.5 and 6, respectively). In the fourth week, both groups showed equal and
      nearly normal pain scores. No case of reactionary post-tonsillectomy haemorrhage
      was recorded in either group. Only one case of secondary post-tonsillectomy
      haemorrhage was recorded, in the potassium titanyl phosphate laser group (2.5 per
      cent), managed conservatively. CONCLUSION: Both the potassium titanyl phosphate
      and the bipolar radiofrequency techniques were safe and easy to use for
      tonsillectomy, with reduced operative time, blood loss and complication rates and
      better post-operative general patient condition. Potassium titanyl phosphate
      laser resulted in reduced operative bleeding and immediate post-operative pain,
      compared with the bipolar radiofrequency technique. However, potassium titanyl
      phosphate laser required slightly more operative time and caused more late post
      operative pain than the bipolar radiofrequency technique. The low rate of
      recorded complications showed that both techniques cause little damage to the
      tonsillar bed during dissection, thus minimising complications.

PMID- 17521474
TI  - Impact of different pH thresholds for 24-hour dual probe pH monitoring in
      patients with suspected laryngopharyngeal reflux.
AB  - OBJECTIVES: The gold standard test for laryngopharyngeal reflux is 24-hour pH
      monitoring, which determines the reflux area index with a pH threshold of less
      than four (i.e. the reflux area index four). However, refluxed pepsin is able to
      cause laryngeal injury at pH levels above five. STUDY DESIGN: Prospective study.
      MATERIALS AND METHODS: In order to establish normative values for a reflux area
      index with a pH threshold of less than five (i.e. the reflux area index five), 29
      healthy volunteers underwent pH monitoring. In 45 patients with suspected
      laryngopharyngeal reflux, reflux area index four and reflux area index five were
      determined by pH study. RESULTS: In healthy volunteers, the reflux area index
      five was 72.6 (95th percentile). In 29 of 44 patients, laryngopharyngeal reflux
      was diagnosed due to a reflux area index four of greater than 6.3. However, the
      reflux area index five revealed laryngopharyngeal reflux in six more patients.
      CONCLUSIONS: For exact analysis of pH monitoring results, two pH thresholds (less
      than four and less than five) must be considered. Further studies with a larger
      number of healthy volunteers are necessary in order to reveal normative values
      for the reflux area index five parameter.

PMID- 17521475
TI  - Dealcoholized red and white wines decrease oxidative stress associated with
      inflammation in rats.
AB  - In vitro experiments have demonstrated that polyphenols exhibit antioxidant and
      anti-inflammatory activities. The present study was designed to test whether
      dealcoholized red (DRW) and white (DWW) wines can decrease the oxidative stress
      associated with inflammation in vivo. Rats were fed for 15 d either a control
      diet or one supplemented with DRW or DWW. Finally, a granuloma was induced by
      subcutaneous administration of carrageenan. Although DRW showed higher
      antioxidant activity in vitro than DWW, both wines decreased the number of cells
      recruited into the granuloma pouch. Malondialdehyde decreased in plasma and
      inflammatory exudate from rats fed with DRW- and DWW-rich diets. Moreover, the
      concentration of NO increased in exudate, which correlates with the increase in
      the citrulline:arginine ratio. Polymorphonuclear leucocytes from the inflammatory
      exudate of rats fed dealcoholized wines showed decreased superoxide anion (O*2)
      production and increased NO production ex vivo. This change in NO production
      resulted from increased expression and activity of inducible NO synthase (EC
      1.14.13.39). Moreover, the up regulation of cyclo-oxygenase-2 (EC 1.14.99.1)
      protein expression observed in rats fed the DRW-rich diet was not related to a
      direct effect of NO. The present results indicate that the non-alcoholic
      compounds of wines not only improve antioxidant status in an inflammatory
      situation, but also limit cell infiltration, possibly through a decrease in O*2
      and an increase in NO production.

PMID- 17521476
TI  - Polymerase chain reaction in the detection of an 'outbreak' of asymptomatic viral
      infections in a community birth cohort in south India.
AB  - Asymptomatic enteric infections are important where sequelae or protection from
      subsequent illness is an outcome measure. The use of reverse transcription
      polymerase chain reaction (RT-PCR) to identify asymptomatic enteric infections in
      a birth cohort followed for rotaviral infections in a south Indian urban slum is
      reported. Of 1191 non-diarrhoeal samples from 371 children collected in May-June
      2003, 22 (1.9%) were positive by ELISA. A total of 147 (40.6%) of 362 samples
      tested by VP6 RT-PCR were positive. In those samples that could be typed, a high
      diversity of G types including G1, G2, G4, G8, G9 and G10, and a high proportion
      (34.4%) of mixed infections were detected. Noroviruses were identified in 6/28
      (21.4%) samples tested. The identification of infections undetectable by
      conventional techniques indicates the importance of the use of sensitive
      diagnostic techniques in research studies. Asymptomatically infected children may
      also act as a source of infection for other susceptible hosts.

PMID- 17521477
TI  - The measurement and magnitude of awareness difficulties after traumatic brain
      injury: a longitudinal study.
AB  - Previous research suggests that reduced self-awareness is common following
      traumatic brain injury (TBI). However, few studies have examined the magnitude of
      this problem in a sample representative of hospitalized individuals. In this
      longitudinal study, individuals with complicated mild to severe TBIs and their
      significant others (SO) were evaluated at 1 and 12 months postinjury on the
      Sickness Impact Profile. Awareness was measured by comparing the level of injury
      related problems reported by a person with TBI and their SO. Overall, individuals
      with TBI did not report fewer difficulties than their SO. In contrast, they
      frequently reported more injury-related difficulties than their SO. As there is
      no commonly or universally accepted definition for differential awareness, the
      magnitude of underreporting and over-reporting problems is presented using four
      different cutoff scores. A minimum discrepancy is proposed for defining awareness
      difficulties that is based on the standard error of measurement of the test
      retest difference of the measure. Reduced self-awareness was inconsistent across
      both time and functional domains. These results suggest that reduced self
      awareness is not the norm at 1 or 12 months postinjury and highlight the need for
      a more standardized approach to the measurement and classification of self
      awareness.

PMID- 17521478
TI  - Cognitive reserve and neuropsychological functioning in patients infected with
      hepatitis C.
AB  - This study evaluated the influence of cognitive reserve on neuropsychological
      test performance in 198 patients infected with the hepatitis C virus. IQ scores,
      educational level, and occupational rating were combined to calculate a Cognitive
      Reserve Score (CRS) for each patient. Similar to studies of infection with the
      human immunodeficiency virus, there was a significantly increased risk of
      impairment in neuropsychological test performance in individuals with lower CRSs.
      It is important to account for CRS when assessing cognitive findings in large
      scale clinical trials.

PMID- 17521479
TI  - Impaired executive functioning in young adults born very preterm.
AB  - Individuals born very preterm (VPT) are at increased risk of perinatal brain
      injury and long-term cognitive and behavioral problems. Executive functioning, in
      particular, has been shown to be impaired in VPT children and adolescents. This
      study prospectively assessed executive function in young adults who were born VPT
      (<33 weeks of gestation) [n = 61; mean age, 22.25 (+/-1.07) years; range, 20.62
      24.78 years] and controls [n = 64; mean age, 23.20 (+/-1.48) years; range, 19.97
      25.46 years]. Tests used comprised the Wechsler Abbreviated Scale of Intelligence
      (WASI), the Hayling Sentence Completion Test (HSCT), the Controlled Oral Word
      Association Test (COWAT), the Animal and Object test, the Trail-Making Test
      (TMT), and the Test of Attentional Performance (TAP). VPT participants showed
      specific executive function impairments in tasks involving response inhibition
      and mental flexibility, even when adjusting for IQ, gender, and age. No
      significant associations were observed between executive function test scores and
      perinatal variables or neonatal ultrasound classification. The results suggest
      that, although free from major physical disability, VPT young adults perform
      worse than controls on tasks involving selective aspects of executive processing,
      such as mental flexibility and response inhibition.

PMID- 17521480
TI  - Treatment of naming in nonfluent aphasia through manipulation of intention and
      attention: a phase 1 comparison of two novel treatments.
AB  - Twenty-three chronic nonfluent aphasia patients with moderate or severe word
      finding impairments and 11 with profound word-finding impairments received two
      novel picture-naming treatments. The intention treatment initiated picture-naming
      trials with a complex left-hand movement and was designed to enhance right
      frontal participation during word retrieval. The attention treatment required
      patients to view visual stimuli for picture-naming trials in their left hemispace
      and was designed to enhance right posterior perisylvian participation during word
      retrieval. Because the intention treatment addressed action mechanisms and
      nonfluent aphasia reflects difficulty initiating or maintaining action (i.e.,
      language output), it was hypothesized that intention component of the treatment
      would enhance re-acquisition of picture naming more than the attention component.
      Patients with moderate and severe word-finding impairment showed gains with both
      treatments but greater incremental improvement from one treatment phase to the
      next with the intention than the attention treatment. Thus, the hypothesis that
      intention component would be a more active constituent than the attention
      component was confirmed for these patients. Patients with profound word-finding
      impairment showed some improvement with both treatments but no differential
      effects for the intention treatment. Almost all patients who showed treatment
      gains on either treatment also demonstrated generalization from trained to
      untrained items.

PMID- 17521481
TI  - Cognitive sequelae in acute respiratory distress syndrome patients with and
      without recall of the intensive care unit.
AB  - Some critically ill patients have dramatic recollections of the intensive care
      unit (ICU), whereas 23-50% have little or no recollection of their ICU stay. In
      addition, cognitive impairments are common following critical illness and ICU
      treatment. Little is known regarding the relationship between cognitive sequelae
      and ICU recall. We assessed recall of the ICU and its relationship to cognitive
      functioning at hospital discharge and 1 and 2 years after discharge in 70
      consecutive acute respiratory distress syndrome (ARDS) patients. Seventeen
      patients (24%) had no recall of the ICU. Patients without ICU recall had
      increased rates of cognitive sequelae at hospital discharge and 1-year follow-up
      compared with the ICU recall group. Patients without ICU recall had a greater
      magnitude of cognitive impairments at hospital discharge, but not at 1- or 2-year
      follow-up. Profile analysis showed significant group differences in general
      intellectual functioning, executive function, processing speed, and spatial
      skills at hospital discharge, but not at 1- or 2-year follow-up. Estimated
      premorbid intelligence scores were inversely related to the magnitude of
      cognitive sequelae, suggesting greater "cognitive reserve" in patients with fewer
      cognitive decrements.

PMID- 17521482
TI  - An investigation of decision making in anorexia nervosa using the Iowa Gambling
      Task and skin conductance measurements.
AB  - The objective of this study is to determine (a) if decision making ability is
      impaired in patients with anorexia nervosa (AN) and in people with good recovery
      from AN and (b) whether any impairment in decision making is associated with
      alterations in skin conductance responses (SCR). Patients with AN (n = 29),
      healthy controls comparable in age and IQ (HC, n = 29), and women long term
      recovered from AN (n = 14), completed the Iowa Gambling Task (IGT) while their
      SCR were measured. AN patients performed poorly in the IGT compared to the HC and
      to the recovered AN participants. AN patients had decreased anticipatory SCR
      prior to choosing cards and reduced SCR after losses compared to HC. IGT
      performance and the SCR of recovered AN participants did not differ from the HC.
      Decision making ability is impaired in AN. It is associated with a significantly
      attenuated SCR. Neither of these features are found in recovered AN. The
      association between impaired decision making ability and a decreased autonomic
      response is consistent with the predictions of the Somatic Marker Hypothesis.

PMID- 17521483
TI  - Cognitive, neurophysiological, and functional correlates of proverb
      interpretation abnormalities in schizophrenia.
AB  - A hallmark of schizophrenia is impaired proverb interpretation, which could be
      due to: (1) aberrant activation of disorganized semantic associations, or (2)
      working memory (WM) deficits. We assessed 18 schizophrenia patients and 18 normal
      control participants on proverb interpretation, and evaluated these two
      hypotheses by examining within patients the correlations of proverb
      interpretation with disorganized symptoms and auditory WM, respectively.
      Secondarily, we also explored the relationships between proverb interpretation
      and a spectrum of cognitive functions including auditory sensory-memory encoding
      (as indexed by the mismatch negativity (MMN) event-related brain potential
      (ERP)); executive function; and social/occupational function. As expected,
      schizophrenia patients produced less accurate and less abstract descriptions of
      proverbs than did controls. These proverb interpretation difficulties in patients
      were not significantly correlated with disorganization or other symptom factors,
      but were significantly correlated (p < .05) with WM impairment, as well as with
      impairments in sensory-memory encoding, executive function, and
      social/occupational function. These results offer no support for disorganized
      associations in abnormal proverb interpretation in schizophrenia, but implicate
      WM deficits, perhaps as a part of a syndrome related to generalized frontal
      cortical dysfunction.

PMID- 17521484
TI  - Schizotypal disorder and schizophrenia: a profile analysis of neuropsychological
      functioning in Japanese patients.
AB  - This study compares neuropsychological functioning in a Japanese schizophrenia
      spectrum disorder group and a group of healthy Japanese volunteers. Participants
      were 37 patients diagnosed with schizophrenia, 28 schizotypal patients, and 99
      psychiatrically-normal volunteers. A wide range of cognitive measures were
      examined. All participants completed a Japanese version of a neuropsychological
      battery assessing executive function, working memory, processing speed, language,
      verbal memory, and spatial organization. Comparisons of neuropsychological
      function demonstrated similarities and differences between patients diagnosed
      with schizotypal disorder and those diagnosed with schizophrenia. Impairments in
      verbal memory, language, and processing speed were common to both patient groups
      and may represent a vulnerability to schizophrenia. Impairments in aspects of
      working memory, spatial organization and executive function were preferentially
      observed in schizophrenia and may be features of the overt manifestation of
      psychosis. Possible differences in the contributions of prefrontal and temporo
      limbic structures provide direction for further studies.

PMID- 17521485
TI  - Cognitive and neuroimaging predictors of instrumental activities of daily living.
AB  - Impaired ability to conduct daily activities is a diagnostic criterion for
      dementia and a determinant of healthcare services utilization and caregiver
      burden. What predicts decline in instrumental activities of daily living (IADLs)
      is not well understood. This study examined measures of episodic memory,
      executive function, and MRI brain volumes in relation to baseline IADLs and as
      predictors of rate of IADL change. Participants were 124 elderly persons with
      cognitive function between normal and moderate dementia both with and without
      significant small vessel cerebrovascular disease. Random effects modeling showed
      that baseline memory and executive function (EXEC) were associated with baseline
      IADL scores, but only EXEC was independently associated with rate of change in
      IADLs. Whereas hippocampal and cortical gray matter volumes were significantly
      associated with baseline IADL scores, only hippocampal volume was associated with
      IADL change. In a model including cognitive and neuroimaging predictors, only
      EXEC independently predicted rate of decline in IADL scores. These findings
      indicate that greater executive dysfunction at initial assessment is associated
      with more rapid decline in IADLs. Perhaps executive function is particularly
      important with respect to maintaining IADLs. Alternatively, executive dysfunction
      may be a sentinel event indicating widespread cortical involvement and poor
      prognosis.

PMID- 17521486
TI  - Reliable change on the Dementia Rating Scale.
AB  - A central role for neuropsychological evaluations is the measurement of change in
      cognitive functioning over time. However, change scores obtained from repeated
      neuropsychological assessments may be affected by normal variability because of
      measurement error and practice effects caused by repeated measurements. The
      current study uses reliable change estimates to establish normative rates of
      change on the Dementia Rating Scale from baseline to first follow-up testing
      among 1080 cognitively normal adults aged 65 and older. Results showed that a 6
      point decline by European Americans or a 9-point decline by African American
      adults within a 9-15 month test-retest interval represents reliable change.
      Within a 16-24-month test-retest interval, a 7-point decline among European
      Americans or an 8-point decline among African American adults represents reliable
      change. In addition, preliminary cross-validation was performed in a clinical
      comparison sample of another 22 older adults. The findings are discussed in the
      context of potential clinical and research applications.

PMID- 17521487
TI  - The relationship of recency discrimination to explicit memory and executive
      functioning.
AB  - Recency discrimination has been conceptualized as an executive ability by some
      investigators and as an aspect of episodic memory by others. We compared the
      performance of 261 neurologically healthy adults on a recency discrimination task
      (RDT) with their performance on measures of executive functioning and explicit
      memory. Mean z-transformed raw scores were used to construct indices of visual
      and verbal explicit memory, fluency, and executive functioning. Analyses revealed
      that RDT performance correlated more closely with visual (r = 0.32; p < 0.001)
      and verbal memory (r = 0.25; p < 0.001) than with fluency (r = 0.16; p < 0.05)
      and executive functioning (r = 0.13; p < 0.05). These findings suggest that
      recency discrimination might be better understood as an aspect of episodic memory
      that is subserved primarily by hippocampal and medial temporal structures than as
      an executive function that is subserved primarily by prefrontal cortex.

PMID- 17521488
TI  - D-KEFS Trail Making Test performance in patients with lateral prefrontal cortex
      lesions.
AB  - This study evaluated cognitive set-shifting in 12 patients with focal lesions in
      the lateral prefrontal cortex (LPC) by examining their performance on the Trail
      Making Test from the Delis-Kaplan Executive Function System (D-KEFS). Patients
      with LPC lesions performed significantly worse than controls on the D-KEFS Trail
      Making Test on the Letter Sequencing, Number-Letter Switching (set-shifting), and
      Motor Speed conditions. Patients with LPC lesions performed significantly more
      slowly on the Number-Letter Switching condition even after controlling for
      performance on the four baseline conditions of the test. In addition, patients
      with LPC lesions exhibited significantly elevated error rates on the Number
      Letter Switching condition. Results suggest that LPC lesions can lead to impaired
      cognitive set-shifting on a visual-motor sequencing task.

PMID- 17521489
TI  - Decision making as measured with the Iowa Gambling Task in patients with
      borderline personality disorder.
AB  - Affective instability is a core dimension of borderline personality disorder. The
      somatic marker hypothesis suggests that emotions play a crucial role in decision
      making. In this preliminary study, decision making was assessed in individuals
      with borderline personality disorder. Patients with borderline personality
      disorder (n = 20) and healthy comparison subjects (n = 15) were tested with the
      Iowa Gambling Task (IGT). The patients showed less advantageous choices on the
      IGT than did the healthy comparison subjects. The results could not be explained
      by indicators of general cognitive function or by symptoms of depression. These
      findings demonstrate that deficits in decision making in borderline personality
      disorder may manifest themselves in an ecologically valid neuropsychological
      test. Future studies should address whether those deficits are related to the
      behavioral characteristics of affective dysregulation and/or impulsivity, to the
      proposed dysfunctions and reduced volume of the orbitofrontal cortex and/or the
      amygdala, and to other neuropsychological functions.

PMID- 17521490
TI  - Impulsive behavior in adults with attention deficit/ hyperactivity disorder:
      characterization of attentional, motor and cognitive impulsiveness.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention
      and/or hyperactivity/impulsivity. Impulsivity persists in adults with ADHD and
      might be the basis of much of the impairment observed in the daily lives of such
      individuals. The objective of this study was to address the presence, and more
      importantly, the three dimensions of impulsivity: attentional, non-planning and
      motor, in how they may relate to neuropsychological mechanisms of impulse
      control. We studied a sample of 50 adults with ADHD and 51 healthy comparison
      controls using the Barratt Impulsivity Scale Version 11 (BIS), and
      neuropsychological tasks, namely the Continuous Performance Task (CPT-II) and the
      Iowa Gambling Task (IGT). The ADHD group showed more signs of impulsivity on the
      three dimensions of BIS, committed more errors of omission and commission on the
      CPT-II, and made more disadvantageous choices on the IGT. These results support
      the existence of deficits related to three components of impulsivity: motor,
      cognitive, and attentional among adults with ADHD. Most importantly, this study
      also highlights the complementary nature of self-report questionnaires and
      neuropsychological tasks in the assessment of impulsivity in ADHD adults.

PMID- 17521491
TI  - Female advantage for object location memory in peripersonal but not extrapersonal
      space.
AB  - The neural representation of peripersonal space may be distinct from the
      representation of extrapersonal space. Sex differences in the performance of
      motor tasks might relate to proximity to the body. In the spatial domain, females
      excel at tasks performed in peripersonal space, like the Object Location Memory
      Task (OLMT), whereas males excel at tasks performed in extrapersonal space, such
      as navigation. We compared performance on the OLMT in peripersonal space with
      performance on the same task in extrapersonal space (using a between-subjects
      design). As predicted, the typical female advantage was observed for the
      peripersonal OLMT. However, for the extrapersonal OLMT, the female advantage
      disappeared and males actually outperformed females. These results suggest that
      the sex differences observed in the OLMT, and potentially other tasks that
      exhibit sex differences in performance, may be related to sex differences to
      spatial-motor systems that are preferentially tuned to proximity.

PMID- 17521492
TI  - Rey Complex Figure: figural and spatial memory before and after temporal
      lobectomy for intractable epilepsy.
AB  - Reliable neuropsychological markers of right temporal integrity have proven
      elusive. Specifically it is unclear whether figural and spatial aspects of visual
      memory are differentially affected by right temporal lobe epilepsy (TLE) and
      subsequent resection. To investigate this we used the modified Rey Complex Figure
      (RCF) scoring system devised by Brier et al. (1996) to obtain separate indices of
      figural and spatial memory in TLE surgery candidates. We extended on their study
      by examining presurgical performance and change following right and left temporal
      lobectomy (RATL, n = 38, LATL, n = 42) in individuals from a cross-institutional
      sample with and without hippocampal sclerosis (HS(+)/HS(-)). Contrary to
      expectation neither figural nor spatial RCF recall were differentially sensitive
      to RTLE, right HS, or subsequent resection. Presurgically, laterality effects on
      both figural and spatial memory indices were not found although HS(-) individuals
      significantly outperformed HS(+) individuals on both measures. Following surgery
      the largest decrements in both figural and spatial recall were observed among
      LATL HS(-) participants. We concluded that RCF recall is a poor marker of right
      temporal lobe function and suggest it may be a "surrogate" measure of left
      temporal lobe function possibly due to the verbalizability of many of its
      components.

PMID- 17521493
TI  - Neuropsychological outcomes in children of mothers with epilepsy.
AB  - The study investigated the nature of the effects of maternal epilepsy on
      cognitive performance of the offspring. One hundred fifty-four children of
      mothers with epilepsy aged 5 to 11 years (study group), along with 130 control
      children, comparable with respect to IQ, socio-economic status, age, and gender
      underwent a neuropsychological assessment using subtests from the NEPSY: A
      Developmental Neuropsychological Assessment, tapping attentional, auditory
      verbal, visuomotor, fine motor, and memory abilities. The study group scored
      significantly lower than the controls on measures of attention, memory, and fine
      motor function. Deficits were more marked in but not limited to the subset of the
      study group exposed to maternal medication in utero. Group differences on
      auditory attention were found only in younger children. Valproate-exposed
      children obtained lower scores on sentence repetition, as well as on the more
      demanding part of a test of auditory attention, than other children in the study
      group, suggesting weaknesses in working memory in the former subgroup.
      Confounding by maternal epilepsy type and polytherapy complicate interpretation
      of this finding. Differences between subsets of children not exposed to anti
      epileptic drugs in utero and controls suggest that both drug exposure and genetic
      factors may contribute to cognitive deficits associated with maternal epilepsy.

PMID- 17521494
TI  - The random number generation task: psychometric properties and normative data of
      an executive function task in a mixed sample.
AB  - We investigated the psychometric properties of the random number generation (RNG)
      task in four studies using a mixed sample of young adults (n = 306), middle-aged
      adults (n = 40), and patients diagnosed with schizophrenia (n = 26). Data in
      study 1 were best accounted for by a three-factor solution representing
      inhibition of stereotypical schemas (seriation), output inhibition (repetition),
      and monitoring of previous output (cycling). Modest test-retest correlations were
      found, with the seriation factor showing acceptable stability across time (study
      2). In study 3, RNG task performance was related to scores on concurrent
      neurocognitive tasks to establish construct validity. RNG scores correlated with
      healthy controls' performance on the Stroop color-word test and patients
      diagnosed with schizophrenia with executive dysfunctions. Patients diagnosed with
      schizophrenia performed poorer on the seriation factor of the RNG than healthy
      control participants (study 4). Our results indicate that the RNG task has modest
      to acceptable psychometric properties. It primarily taps executive subfunctions
      (i.e., inhibition, updating, and monitoring), which are affected by
      psychopathological or neurological deficits.

PMID- 17521495
TI  - Reward context sensitivity impairment following severe TBI: an event-related
      potential investigation.
AB  - Many rehabilitation protocols following traumatic brain injury (TBI) utilize
      reinforcement and reward to influence behavior and facilitate recovery; however,
      previous studies suggest survivors of severe TBI demonstrate impairments in
      contingency utilization and sensitivity. The precise neurobiological mechanisms
      underlying these deficits have not been thoroughly explored, but can be examined
      using the "feedback-related negativity" (FRN)--an event-related potential (ERP)
      component evoked following performance or response feedback (e.g., whether a
      monetary reward is obtained) with a larger FRN following unfavorable than
      favorable outcomes--particularly when unfavorable feedback occurs in the context
      of high reward probability. We examined ERPs elicited by favorable (monetary
      gain: "reward") and unfavorable (no monetary gain: "non-reward") feedback during
      a guessing task where probability of reward outcome was manipulated in survivors
      of severe TBI and demographically matched healthy participants. Consistent with
      previous findings, controls showed larger amplitude FRN to non-reward feedback
      and the largest amplitude FRN following a non-reward when reward probability
      context was greatest. In contrast, FRN in TBI participants did not significantly
      differentiate non-reward from reward trials and their FRN was largest to reward
      trials in the low reward probability context. Findings implicate an
      electrophysiological marker of impaired reward context sensitivity following
      severe TBI.

PMID- 17521496
TI  - Humor comprehension in older adults.
AB  - The goal of this study was to understand factors related to humor comprehension
      in old age. This study proposes that, in contrast to younger adults, older adults
      have greater difficulty with humor comprehension due to age-related cognitive
      decline. Tests of verbal and nonverbal humor comprehension and tests of cognitive
      flexibility, abstract reasoning, and short-term memory were administered to 40
      younger and 41 older adults. In general, older adults scored lower than younger
      adults on tests of humor and cognitive abilities. Regression analyses support the
      idea that cognition affects humor comprehension, but the relative contribution of
      each specific mechanism remains unclear. The results of this study suggest that
      there may be age-related deficits in humor comprehension, but more importantly,
      that a more sophisticated model is needed to clarify the role of cognition in
      humor comprehension. Humor comprehension warrants further study because of the
      potential physical and psychological benefits of humor.

PMID- 17521497
TI  - Sleep apnea: implications for heart failure.
AB  - It is likely sleep apnea is highly prevalent in patients with congestive heart
      failure (CHF). However, as awareness is low and consensus guidelines do not
      exist, sleep apnea is not routinely screened for or diagnosed in CHF practice.
      Untreated sleep apnea may promote fatigue as well as left ventricular
      dysfunction, disease progression, and increased mortality. Available screening
      tools lack sensitivity or specificity, and there are insufficient numbers of
      sleep laboratories to accommodate the potentially large number of patient
      referrals with CHF for definitive diagnosis. In CHF patients with obstructive
      sleep apnea and sleepiness, treatment includes continuous positive airway
      pressure which may improve left ventricular function; optimal treatment for the
      non-sleepy patient is not established. There is no consensus regarding treatment
      for central sleep apnea. Studies which evaluate cardiovascular endpoints will be
      necessary to define management strategies for patients with CHF and either
      obstructive or central sleep apnea.

PMID- 17521498
TI  - The impact of diabetes on heart failure: opportunities for intervention.
AB  - The pathophysiologic processes of diabetes mellitus and heart failure are likely
      interrelated. In particular, hyperglycemia and insulin resistance can induce
      myocardial contractile systolic and diastolic abnormalities at the cellular
      level. Furthermore, patients with heart failure and concomitant diabetes mellitus
      are more likely to have underlying comorbid conditions resulting in greater
      vulnerability to adverse consequences. It is reassuring that the majority of
      patients with diabetes mellitus and heart failure respond to standard heart
      failure medical regimens comparable to their nondiabetes counterparts. However,
      the safety profiles of current antidiabetic medications are far from ideal when
      used in patients with heart failure. Emerging novel therapies that reverse the
      metabolic and structural changes induced by the diabetic milieu are currently
      under clinical development, and their potential benefits may even extend beyond
      the diabetic population.

PMID- 17521499
TI  - Atrial fibrillation and congestive heart failure: a two-way street.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia
      encountered in clinical cardiology, particularly in patients with heart failure.
      Its prevalence increases with the degree of left ventricular dysfunction and
      severity of heart failure symptoms. The development of AF in the setting of heart
      failure has been shown to result in increased mortality. Studies thus far
      indicate that rhythm control with antiarrhythmic drug therapy or catheter
      ablation offers both symptomatic and probably survival advantage in patients with
      heart failure and AF. In patients with permanent AF, the effects of restoring a
      regular ventricular response with atrioventricular junction ablation followed by
      biventricular pacing remain to be shown. In the current manuscript, we will
      review the proposed mechanisms of increased morbidity and mortality associated
      with AF and the current treatment options including the roles of radiofrequency
      ablation and pacing.

PMID- 17521500
TI  - Nutrition and cardiomyopathy: lessons from spontaneous animal models.
AB  - Spontaneously occurring dilated cardiomyopathy in dogs and hypertrophic
      cardiomyopathy in cats are common diseases and are vastly underutilized as models
      of human cardiac disease. The goals of nutrition are no longer limited to a low
      sodium diet, as research is now showing that nutrients can modulate disease and
      be an important adjunct to medical therapy. Deficiencies of certain nutrients can
      contribute to cardiomyopathies, as with taurine, but some nutrients-such as n-3
      fatty acids, carnitine, and antioxidants-may have specific pharmacologic
      benefits. Dogs and cats with spontaneous cardiomyopathies are an exciting and
      promising model for studying nutritional modulation of cardiac disease.

PMID- 17521501
TI  - Beta-blocker contraindications: are there patients or situations where use is
      inappropriate?
AB  - beta-blockers have been conclusively proven to increase survival and improve
      symptoms of heart failure, yet there is underutilization of these agents most
      commonly because of misunderstandings of the relative contraindications and
      adverse events during treatment. In this manuscript, we discuss the potential
      contraindications to beta-blockers in heart failure and compare the true risks
      against the significant benefits.

PMID- 17521502
TI  - Beta-blockers to prevent symptomatic heart failure in patients with stage A and B
      heart failure.
AB  - beta-blockers have been well-studied in the treatment of the symptomatic stages
      of chronic heart failure. Frequently physicians treat patients with asymptomatic
      left ventricular (LV) dysfunction and patients with hypertension on beta-blockers
      without clear evidence that there is value in doing so. Chronic heart failure
      poses an extraordinary economic burden; any effective therapy that limits the
      progression to symptomatic heart failure can probably reduce monetary
      expenditures in addition to potentially reducing morbidity and mortality. In this
      article, we review the available literature on using beta-blockers in stage A and
      B heart failure to prevent progression to the symptomatic stages. The literature
      reveals that there is no benefit in using beta-blockers to treat essential
      hypertension. In patients who experience LV dysfunction post-myocardial
      infarction, even if asymptomatic, there is improved mortality and a trend toward
      a reduction in progression to symptomatic heart failure. In patients with
      asymptomatic chronic LV dysfunction there are data that beta-blockers reduce LV
      dimensions and improve ejection fraction. Patients with hypertension should not
      be given beta-blockers as primary treatment. All patients with asymptomatic LV
      dysfunction should be treated with a beta-blocker, regardless of whether they
      experienced myocardial infarction.

PMID- 17521503
TI  - Heart transplantation: assessment of heart failure mortality risk.
AB  - Heart failure (HF) presents with a wide spectrum of disease severity and with a
      broad risk of associated morbidity and mortality. Identification of individuals
      at high risk for HF death is important for assessment of candidacy for heart
      transplantation and mechanical circulatory assistance and, more broadly, for
      guiding pharmaceutical, surgical, or palliative interventions. In this article,
      we review and compare several of the HF risk prediction tools currently
      available, highlighting their clinical utilities and potential shortcomings. Risk
      prediction tools must be carefully selected, recognizing that their accuracy is
      likely to be greatest when used in patients most similar to those from whom the
      tool was developed. As HF is a dynamic condition, serial risk assessment at
      regular intervals and as patient clinical status changes is warranted, although
      clinical evidence to support this practice is limited.

PMID- 17521504
TI  - Tips and tricks on outpatient initiation and uptitration of beta-blockade in
      heart failure.
AB  - beta-blockade has a therapeutic role across the continuum of patients with heart
      failure (HF), with a demonstrated mortality benefit in stage II and III HF.
      Concerns regarding initiation and uptitration linger as patients with resting
      bradycardia, pulmonary, or vascular disease are often unnecessarily excluded from
      receiving therapy. We will review the risk data on beta-blockade and offer
      therapeutic strategies to help overcome residual barriers to the initiation and
      uptitration of this important therapy in patients with HF.

PMID- 17521505
TI  - Extending DXA beyond bone mineral density: understanding hip structure analysis.
AB  - The hip structure analysis (HSA) method was introduced to extract geometric
      strength information from archived hip dual-energy x-ray absorptiometry (DXA)
      scans acquired in large research studies. Research has shown that strength
      effects are not easily inferred from conventional DXA measures, so there is
      growing interest in the clinical community in more direct evaluation of bone
      strength in patients. This article reviews the factors that govern the strength
      of an object, how they are used in engineering simulations, and how those
      properties can be extracted from DXA data. It is important to recognize that that
      although DXA scanners can be used to measure geometric strength, they were not
      designed to do so. The current HSA method is fundamentally limited to evaluating
      bending strength in the plane of the image, so precision is sensitive to
      consistent femur positioning. The positioning issue and other limitations of the
      HSA method are discussed, as well as the critical importance of body-size scaling
      when interpreting bone geometry. Also discussed is how current HSA limitations
      could be ameliorated in a "next-generation" DXA scanner that is optimized for the
      purpose.

PMID- 17521506
TI  - Effects of microarchitecture on bone strength.
AB  - Bone strength and stiffness depend strongly on bone mass, but they also depend on
      the microarchitecture and tissue quality of both cancellous and cortical bone.
      All these aspects differ between individuals and between anatomic sites. This
      review discusses ways to characterize the three-dimensional cancellous
      architecture as well as changes in architecture and bone composition caused by
      bone remodeling. The methods used range from detailed descriptions of sizes and
      distances in cancellous bone to coarser texture analysis methods using clinical
      data. As the resolution of clinical images increases, it may become possible to
      use knowledge of the relationship between bone microarchitecture and strength to
      predict fracture risk clinically.

PMID- 17521507
TI  - The role of the collagen matrix in skeletal fragility.
AB  - The collagen network in bone provides resistance against fracture and may be
      susceptible to changes with aging and disease. This review identifies the changes
      in quality of collagen matrix as contributors to bone fragility. With aging and
      in diabetes, cross-links accumulate in bone collagen as a result of nonenzymatic
      glycation and consequently impair matrix properties, increasing bone fragility.
      Cell-culture and animal studies suggest that the accumulation of cross-links
      induced by nonenzymatic glycation may be related to a reduction in bone turnover
      resulting from the altered responses of osteoblasts and osteoclasts to advanced
      glycation end products.

PMID- 17521508
TI  - Novel osteoclast signaling mechanisms.
AB  - Osteoclasts are cells of monocyte/macrophage origin that degrade bone matrix.
      Receptor activator of NF-kappaB ligand (RANKL) induces osteoclast differentiation
      in the presence of macrophage colony-stimulating factor. RANKL activates the
      tumor necrosis factor receptor-associated factor 6, c-Fos, and calcium signaling
      pathways, all of which are indispensable for the induction and activation of
      nuclear factor of activated T cells (NFAT) c1. NFATc1 is the master transcription
      factor for osteoclast differentiation, which regulates many osteoclast-specific
      genes. Multiple immunoglobulin-like receptors associated with immunoreceptor
      tyrosine-based activation motif (ITAM)-harboring adapters, Fc receptor common chi
      subunit (FcRgamma), and DNAX-activating protein (DAP) 12 mediate costimulatory
      signals for RANK, which activate calcium signaling through phospholipase Cgamma
      (PLCgamma). In addition to calcineurin-NFATc1, calcium signaling activates the
      CaMK-CREB (calcium/calmodulin activated kinase-cyclic AMP-response element
      binding protein) pathway, which also plays a critical role in osteoclastogenesis.
      This review summarizes recent advances in the study of signaling mechanisms of
      osteoclast differentiation.

PMID- 17521509
TI  - Wnt signaling and the regulation of bone mass.
AB  - Human genetic studies have firmly established a link between bone mass in humans
      and gain-of-function or loss-of-function mutations in a Wnt coreceptor, low
      density lipoprotein receptor-related protein 5 (LRP5), or in the Wnt antagonist
      sclerostin, and several molecular genetic studies in mice have consistently
      confirmed the critical importance of the Wnt signaling pathway in skeletal
      biology and disease. In what may be a novel paradigm, the ubiquitous nature of
      LRP5/6 and Wnt signaling is counterbalanced by the bone-restricted and regulated
      expression of Wnt antagonists such as sclerostin and Dickkopf-1 (Dkk1) in adult
      tissues, offering new and potentially safe therapeutic means of intervention to
      stimulate bone formation.

PMID- 17521510
TI  - The biology of osteocytes.
AB  - Osteocytes, the most abundant cell type in bone, remain the least characterized.
      Several theories have been proposed regarding their function, including
      osteolysis, sensing the strains produced in response to mechanical loading of
      bones, and producing signals that affect the function of osteoblasts and
      osteoclasts and hence, bone turnover. This review also discusses the role of
      osteocyte apoptosis in targeted bone remodeling and proposes that the occurrence
      of osteocyte apoptosis is consistent with the description of apoptosis as an
      essential homeostatic mechanism for the healthy maintenance of tissues.

PMID- 17521511
TI  - Serotonin transporter polymorphism and stress: a view across the lifespan.

PMID- 17521512
TI  - Atypical antipsychotic medication in preschool children.

PMID- 17521513
TI  - Cycloid psychosis: an examination of the validity of the concept.
AB  - The diagnosis of cycloid psychosis has a long tradition in European psychiatry.
      However, it has been poorly assimilated within the DSM IV and ICD-10 diagnostic
      systems. Leonhard set the basis for the current conceptualization of the
      disorder, and Perris and Brockington developed the first operational diagnostic
      criteria. However, the two conceptualizations of the disorder are not the same
      and differ across a number of meaningful variables. Cycloid psychosis is a useful
      concept in that it possesses both clinical and predictive validity. Despite the
      high prevalence of mood symptoms and syndromes, cycloid psychosis does not equal
      schizoaffective disorder. Although a substantial body of evidence suggests that
      cycloid psychosis differs meaningfully from typical schizophrenia, it is less
      clear whether it differs from major mood disorders or represents an independent
      nosological entity. The existence of putative subtypes is also likely, and the
      differentiation between affective and nonaffective subtypes has received some
      support.

PMID- 17521514
TI  - Neurophysiology of synesthesia.
AB  - Synesthesia is an experience in which stimulation in one sensory or cognitive
      stream leads to associated experiences in a second, unstimulated stream. Although
      synesthesia is often referred to as a "neurological condition," it is not listed
      in the DSM IV or the ICD classifications, as it generally does not interfere with
      normal daily functioning. However, its high prevalence rate (one in 23) means
      that synesthesia may be reported by patients who present with other psychiatric
      symptoms. In this review, I focus on recent research examining the neural basis
      of the two most intensively studied forms of synesthesia, grapheme --> color
      synesthesia and tone --> color synesthesia. These data suggest that these forms
      of synesthesia are elicited through anomalous activation of color-selective
      areas, perhaps in concert with hyperbinding mediated by the parietal cortex. I
      then turn to questions for future research and the implications of these models
      for other forms of synesthesia.

PMID- 17521515
TI  - Folie a deux and shared psychotic disorder.
AB  - Folie a deux (FAD) was first described in 19th century France. Since then, the
      concept has been elaborated, and several subtypes of FAD have been successively
      reported in France. In contrast, studies in German-speaking psychiatry mainly
      focused on the conceptual boundary between reactive/endogenous psychosis and
      etiological hypothesis (ie, psychogenesis vs genetic predisposition). In North
      America, Gralnick wrote a seminal review and redefined four subtypes of FAD by
      adopting the European classical concepts. More recently, "shared psychotic
      disorder" in DSM or "induced delusional disorder" in ICD-10 was branched off from
      FAD. However, several classical subcategories of FAD were not included in these
      recent definitions, the nosological significance of which should not be
      underestimated. We examined demographic data of FAD case reports published from
      the 19th to the 21st century and found that some of the earlier hypotheses, such
      as females being more susceptible, older and more intelligent individuals being
      more likely to be inducers, and sister-sister pairs being the most common
      relationship, were not supported. The controversial issue of the etiology of FAD
      association of subjects or genetically driven psychosis-was re-examined in light
      of recent studies.

PMID- 17521516
TI  - Auditory hallucinations in those populations that do not suffer from
      schizophrenia.
AB  - The following article discusses the phenomenon of auditory hallucinations in
      those who do not suffer from schizophrenia. Research has shown the occurrence of
      auditory hallucinations in the general population to such an extent that they
      cannot be said to be pathognomonic of psychiatric illness. In addition, it has
      long been known that certain hallucinatory experiences occur in health, such as
      hypnagogic and hypnopompic hallucinations. However, there are fundamental
      differences in the characteristics of these experiences. In the psychiatric
      population, these tend to be frequent, intrusive, and distressing. In contrast,
      in the nonclinical population, these are often predominantly positive and
      nonthreatening. The exact mechanism for the occurrence of auditory hallucinations
      is not yet known, but it is hoped that through the study of those in health, the
      mechanisms that underpin pathophysiologic processes in clinical conditions also
      can be elucidated.

PMID- 17521517
TI  - Prevalence of PTSD following surgical amputation.

PMID- 17521518
TI  - Medical comorbidity and alcohol dependence.
AB  - Alcohol dependence (AD) and, more generally, alcohol use disorders (AUDs)
      predispose individuals to adverse consequences that extend beyond the expected
      damage from alcohol-direct toxicity. Research has shown that the relationship of
      alcohol use to health outcomes is complex, as is the etiology of AD, and that the
      individual and social costs of alcohol-related problems are increasing. We review
      advances in alcohol science that explore the role of alcohol consumption and
      patterns of drinking in a range of medically comorbid conditions. Although new
      knowledge can assist in the development of appropriate medical management
      strategies, AUDs account for an important percentage of the global burden of
      disease and require approaches that are not uniquely focused on the
      identification and treatment of AD.

PMID- 17521519
TI  - Recent advances in poststroke depression.
AB  - Depression is the most common psychiatric complication after stroke. Its
      prevalence varies from 20% to 80%, and it is underdiagnosed and undertreated. It
      has significant impact on rehabilitation, motor recovery, activities of daily
      living, social and interpersonal life, and mortality. Several studies have shown
      that biological and psychosocial factors play significant roles in the
      development of this disabling disease. Recent research shows that neurochemical
      processes also may play some role in the pathophysiology of this condition.
      Several trials have shown evidence that the older, as well as newer
      antidepressants and psychostimulants may reduce/prevent depressive symptoms after
      stroke. At this point there are no clear guidelines available to choose safe and
      effective treatments. Drugs are selected based on their efficacy and side effect
      profile in these patients. More research is needed to understand the
      pathophysiology of depression after stroke. There also is a need for more
      randomized clinical trials to better treat patients with this condition.

PMID- 17521520
TI  - Mania in the medically ill.
AB  - Manic symptoms frequently occur in patients with comorbid medical disorders and
      present a diagnostic and treatment challenge. Manic symptoms may be due to an
      independent psychiatric illness, may be induced or precipitated by a medical
      condition, or may result from medication or substance use. The presence of manic
      symptoms in medically ill patients can lead to misdiagnosis or complicate the
      management of comorbid medical illness. It is of paramount importance to identify
      the etiology of the mania and, in particular, differentiate primary from
      secondary mania. Management of mania in the medically ill should focus on
      treating the underlying medical condition, medication management (antipsychotic
      agents, mood stabilizers, and/or benzodiazepines), and psychotherapy (if needed).
      Selecting appropriate medication for treatment requires basic knowledge of the
      pharmacokinetics of the medications, their side effect profile, and drug-drug
      interaction. The majority of deficits accompanying secondary mania resolve with
      treatment of the underlying cause, and supportive psychopharmacology may be all
      that is needed, but if symptoms persist, patients may need medications for a
      longer duration.

PMID- 17521521
TI  - Psychogenic polydipsia review: etiology, differential, and treatment.
AB  - Psychogenic polydipsia (PPD), a clinical disorder characterized by polyuria and
      polydipsia, is a common occurrence in inpatients with psychiatric disorders. The
      underlying pathophysiology of this syndrome is unclear, and multiple factors have
      been implicated, including a hypothalamic defect and adverse medication effects.
      Hyponatremia in PPD can progress to water intoxication and is characterized by
      symptoms of confusion, lethargy, and psychosis, and seizures or death. Evaluation
      of psychiatric patients with polydipsia warrants a comprehensive evaluation for
      other medical causes of polydipsia, polyuria, hyponatremia, and the syndrome of
      inappropriate secretion of antidiuretic hormone. The management strategy in
      psychiatric patients should include fluid restriction and behavioral and
      pharmacologic modalities.

PMID- 17521522
TI  - Completed suicide in medical/surgical patients: who is at risk?
AB  - Factors contributing to patients killing themselves while admitted to general
      hospital medical/surgical (med/surg) units have not been well described. These
      rare yet devastating suicides appear to have characteristics distinguishing them
      from suicides in psychiatric inpatients. This article emphasizes the importance
      of both agitation and readily available lethal means in suicides that are almost
      invariably impulsive. It also emphasizes how traditional risk factors such as
      past history of psychiatric illness, substance abuse, or suicidality typically
      are absent in this population, as are present depression and known suicidality.
      Caregivers seeking to prevent suicide in the med/surg environment therefore must
      appreciate the potential lethality of acute psychic and motoric agitation. Close
      surveillance of agitated patients, with interventions to calm them and secure
      their surroundings, will assure safety and save lives.

PMID- 17521523
TI  - Sexual dysfunction in the medically ill.
AB  - Common in the medically ill, sexual dysfunction results from disruption of one or
      more stages of the sexual response cycle. Increased understanding of sexual
      pathophysiology and the psychosocial forces whereby diseases impede normal
      function promotes more informed treatment choices. This review focuses on the
      pathophysiology, impact, and treatment options of sexual dysfunction in men and
      women with spinal cord injuries, multiple sclerosis, dementia, hypertension,
      heart disease, stroke, cancer, and HIV/AIDS.

PMID- 17521524
TI  - Interferon-induced depression in hepatitis C: an update.
AB  - Hepatitis C is a global epidemic, and its costs in both lives and health care
      expenditures continue to rise. The only approved treatment for this disease,
      interferon-alpha (IFN), causes treatment-emergent depression in more than one
      quarter of all patients who take it. Newer preparations of IFN have been
      developed to increase its antiviral efficacy, but the incidence of treatment
      emergent depression has not decreased. The data on the epidemiology and risk
      factors for interferon-induced depression are reviewed in an effort to delineate
      its standing as a unique psychiatric disorder. In addition, evidence-based
      treatment approaches are outlined, including the potential efficacy of
      preinterferon prophylactic treatment with antidepressants.

PMID- 17521525
TI  - Progression and remission of nephropathy in type 2 diabetes: new strategies of
      treatment and monitoring.

PMID- 17521526
TI  - The effect of hyperventilation upon cerebral blood flow and metabolism in
      patients with fulminant hepatic failure.
AB  - Patients with FHF have a high risk of cerebral edema and intracranial
      hypertension. The pathophysiological background for this phenomenon is not
      completely settled, but alteration in CBF as well as cerebral metabolism seems to
      be of importance. Mechanical hyperventilation has a prompt effect on intracranial
      pressure. This effect is assumed to be caused by the hypocapnia induced alkalosis
      which produces vasoconstriction and thereby a decrease in CBF and cerebral blood
      volume. It has been stated that hyperventilation may be harmful to patients with
      FHF, but only few studies have addressed the effect of hyperventilation upon
      cerebral metabolism. In the present clinical studies we evaluated the effect of
      short-term mechanical hyperventilation upon cerebral circulation and metabolism
      in patients with FHF. Although global CBF was reduced in patients with FHF it
      tightly matched the cerebral oxidative requirements. Already in the early phase
      of FHF there was a prominent cerebral efflux of glutamine that could not be
      accounted for by cerebral ammonia uptake. Moderate hyperventilation reduced
      global CBF without compromising cerebral oxidative metabolism. In addition,
      moderate hyperventilation restored cerebral autoregulation in most patients with
      FHF, and normalised the cerebral nitrogen balance during short-term
      interventions. Studies of global and regional cerebral carbon dioxide reactivity
      showed normal global as well as regional cerebral carbon dioxide reactivity in
      almost all patients with FHF. However, cerebral perfusion in frontal brain
      regions as well as basal ganglia is low in FHF as compared to healthy subjects,
      which may make these regions at risk of hypoperfusion during pronounced
      hyperventilation. It is concluded that moderate short-term hyperventilation does
      not compromise cerebral oxidative metabolism. Recommendation of its prolonged use
      in FHF awaits further studies. Furthermore, the data of this thesis demonstrates
      that alterations in cerebral glutamine and ammonia metabolism precedes increases
      of CBF, which seems to be a phenomenon that takes place later during the disease
      course, i.e., immediately before intracranial pressure is rising.

PMID- 17521527
TI  - Alloreactivity as therapeutic principle in the treatment of hematologic
      malignancies. Studies of clinical and immunologic aspects of allogeneic
      hematopoietic cell transplantation with nonmyeloablative conditioning.
AB  - Allogeneic hematopoietic cell transplantation (HCT) represents a potentially
      curative treatment modality in a range of hematologic malignancies. High-dose
      myeloablative radio-chemotherapy has conventionally been used as part of the
      preparative regimen before HCT for two reasons: it has a profound
      immunosuppressive effect on the host, limiting the ability to reject the graft
      and it has substantial anti-tumor efficacy. Graft rejection is an example of
      alloreactivity as alloreactivity denotes the immunologic reactions that occur
      when tissues are transplanted between two individuals within the same species. If
      the immune system of the host is suppressed to a degree where rejection does not
      occur, the possibility arises that immunocompetent donor cells can attack the
      recipient tissues. This phenomenon is termed Graft-versus-Host disease (GVHD) if
      healthy tissues of the host are attacked and the Graft-versus-Tumor (GVT) effect
      if the malignant cells are the targets of the reaction. Clinical studies have
      shown that patients who develop GVHD have a lower risk of relapse of the
      malignant disease and that donor lymphocyte infusion can induce durable
      remissions in patients with relapsed disease following the transplant. These
      observations indicate that a GVT effect can be present following allogeneic HCT
      and that this effect, like GVHD, is an alloreactive response. The toxicity of HCT
      with myeloablative conditioning is considerable and this limits the use of this
      procedure to patients below 50-60 years of age. A large proportion of the
      patients with hematologic malignancies are older than 60 years at diagnosis and
      they are therefore not eligible for this treatment. During the last decade,
      conditioning regimens that are nonmyeloablative or have reduced intensity have
      been developed. The purpose of this development has been to extend the use of
      allogeneic HCT to older patients and to patients who due to the malignant disease
      or to comorbidities are unable to tolerate myeloablative conditioning. In
      allogeneic HCT with nonmyeloablative conditioning the curative potential relies
      entirely on the ability of the donor cells to elicit a GVT effect. Allogeneic HCT
      with nonmyeloablative conditioning was introduced at Department of Hematology at
      Rigshospitalet in March 2000. The results of this treatment modality have been
      promising and we and others have shown that durable remissions can be obtained in
      patients who are heavily pretreated. One of the goals of allogeneic HCT with
      nonmyeloablative conditioning was to perform both the actual transplant procedure
      and the clinical follow up in the outpatient setting. In the first 30 patients
      transplanted at Rigshospitalet, we observed that the transplant itself and the
      first weeks post transplant could be performed as an outpatient procedure in a
      number of patients. However, all the patients were admitted and the median
      duration of hospitalization was 44 days during the first year post transplant.
      Complications such as infections and GVHD were common causes of hospitalization
      and studies from other centers have shown that infections, GVHD and relapse of
      the malignancy are the major obstacles to a good result of allogeneic HCT with
      nonmyeloablative conditioning. One way to improve the results of this treatment
      would therefore be to reduce the incidence of GVHD without compromising the GVT
      effect. In HCT with nonmyeloablative conditioning the relatively well-defined
      antineoplastic effect of high-dose myeloablative radio-chemotherapy is
      substituted with the alloreactive effect of the donor cells. Because the level of
      alloreactivity varies widely between different donor-recipient pairs, the ability
      to monitor the level of alloreactivity following the transplant would therefore
      be desirable. To this end we have investigated the ability of different
      immunologic and molecular methods to quantify the level of ongoing alloreactivity
      following the transplant. By simultaneous determination of the fraction of T
      cells of donor origin (donor T-cell chimerism) and the total number of T cells in
      the peripheral blood, we observed that patients with a high number of donor CD8 +
      T cells on day +14 had a high risk of acute GVHD. Other studies have shown that
      the level of donor T-cell chimerism early after transplant predicts the
      development of acute GVHD. One way to exploit this knowledge could be to
      individualize the pharmacologic immunosuppression given post transplant. This
      immunosuppression is given primarily to prevent the development of GVHD but may
      also inhibit the GVT effect. In patients with a low risk of GVHD early tapering
      of the immunosuppression could be done, while the period of immunosuppression
      could be extended in patients with a high risk of GVHD. In this way the GVT
      effect could theoretically be optimized in each patient and the results of the
      treatment improved. In another study we used limiting dilution analysis to
      monitor the frequencies of interleukin (IL)-2 producing helper T cells responding
      to recipient or donor antigens following the transplant. The conclusion from this
      study was that both the technical performance and the data analysis were to
      complex for this method to be used as a routine clinical tool. However, the study
      showed that immune responses following HCT are subject to a tight regulation and
      suggested that this regulation could be due to regulatory cell populations. Such
      regulatory cell populations have been used successfully in animal models to treat
      acute GVHD. The secretion of cytokines is an important aspect of immune
      responses. We analyzed cytokine gene expression in mononuclear cells obtained
      from patients and donors before and after HCT. Patients with acute GVHD had lower
      levels of IL-10 mRNA on day +14 than patients who did not develop acute GVHD.
      Patients who experienced progression or relapse of the malignant disease were
      characterized by higher levels of IL-10 mRNA before the transplant than patients
      who remained in remission. The conclusion of this study was that IL-10 might be
      an inhibitor of alloreactivity following allogeneic HCT with nonmyeloablative
      conditioning. Allogeneic HCT with nonmyeloablative conditioning represents a
      major step forward in the treatment of patients with hematologic malignancies.
      However, many issues such as whom to transplant and when the transplant should be
      performed remain to be clarified. Large prospective studies, involving
      collaboration between centers, are needed to define the role of HCT with
      nonmyeloablative conditioning along with other treatment modalities. In addition,
      it is important to continue to elucidate the immunologic mechanisms that are
      responsible for GVHD and the GVT effect.

PMID- 17521528
TI  - Denmark's global responsibility--Danish development policy.
AB  - Global health issues have increasingly become the focus of the global development
      agenda. In particular attention has increased on epidemics of infectious
      diseases, an area where the increase in financial assistance also has been most
      pronounced. The article focuses on the need to strike a balance between combating
      large-scale epidemics and ensuring the necessary structures for delivering
      general health care services for the entire population. Examples are given of how
      Danish development assistance contributes to ensuring such outcomes.

PMID- 17521529
TI  - The framework of international health research--secondary publication.
AB  - Of the global budget for health research, only 10% is spent on the disease burden
      of 90% of the world's population. Investments in international health research
      are lacking, hampering health of the poor in particular. Effective vaccines
      against the world killers HIV, malaria and tuberculosis still do not exist.
      However, besides scaling up research for new drugs and vaccines, research in
      health care systems are needed to understand the obstacles to implement new as
      well as existing interventions to prevent and combat the major health problems of
      those most in need. The task demands political and private sector commitment.

PMID- 17521530
TI  - Pre- and postgraduate education in international health--secondary publication.
AB  - The aim of this article is to provide information about possibilities for medical
      students and doctors to obtain knowledge about international health. Increasing
      globalisation requires knowledge about international health in such a way that
      Danish doctors are able to diagnose and treat patients, regardless of the
      patient's nationality and ethnic background. Denmark has a global responsibility
      towards low and middle income countries to increase the standard of health.
      Increased knowledge and research in these countries are important both at an
      undergraduate and postgraduate level.

PMID- 17521531
TI  - International health at home: learning from low-income countries--secondary
      publication.
AB  - International health research conducted under extreme conditions in low-income
      countries may question assumptions which are also important in high-income
      countries. Examples are given of how observations in Guinea-Bissau have led to
      reinterpretation of the decline in measles mortality in the industrialised
      countries, the polio model and the impact of stopping vaccinations after
      eradication.

PMID- 17521532
TI  - Child and adolescent health and development in a European perspective--a new WHO
      strategy--secondary publication.
AB  - In general, children and adolescents in the WHO European Region today have better
      nutrition, health and development than ever before. There are striking
      inequalities in health status across the 52 countries in the Region, however,
      with over ten-fold differences in infant and child mortality rates. Inequalities
      are also growing within countries, and several health threats are emerging.
      Against this background, the WHO Regional Office for Europe has developed a
      European strategy for child and adolescent health and development. The purpose of
      the Strategy, together with a tool kit for implementation, is to assist member
      states in formulating their own policies and programmes.

PMID- 17521533
TI  - Sex-differential responses to preventive health interventions. Maybe we treat
      boys and girls differently when we treat them equally?--Secondary publication.
AB  - It is well recognised that boys and girls differ with respect to morbidity, for
      instance boys more often suffer from respiratory infections and asthma, whereas
      girls are more susceptible to celiac disease and insulin resistance/type II
      diabetes. Nonetheless, there are very few studies which have addressed the
      potential differences in boys' and girls' immune systems. From our perspective of
      long-term research in low-income countries, it is problematic that we implement
      preventive health interventions and treatments which influence the immune system
      without investigating whether there are sex-differences in the response to these
      interventions.

PMID- 17521534
TI  - Consequences of collective violence with particular focus on the gender
      perspective--secondary publication.
AB  - There is increasing focus on the gender perspective related to the consequences
      of collective violence. Women run a greater risk of being victims of sexual
      violence, but few studies have focused on gender differences with respect to
      physical violence, sexual violations and the impact on health. Further research
      is needed on these issues as well as on the identification of evidence based
      interventions.

PMID- 17521535
TI  - The metabolic syndrome in a global perspective. The public health impact-
      secondary publication.
AB  - The term "metabolic syndrome" refers to the clustering of a number of
      cardiovascular risk factors (obesity, hypertension, dyslipidemia and
      hyperglycaemia) believed to be related to insulin resistance. The prevalence of
      each of these diseases as well as the metabolic syndrome is increasing world
      wide. Obesity, hypertension, dyslipidemia and diabetes are no longer diseases of
      the wealthy. By 2025, three out of four people with diabetes will be living in
      third world countries, and similar trends are likely for the other components of
      the syndrome. Preventive action is urgently needed, and studies in China and
      India have proven to be effective.

PMID- 17521536
TI  - Global development of resistance--secondary publication.
AB  - Antibiotic resistance is an increasing problem world wide, although in some areas
      the increase in resistance is slow, as in the Nordic countries. Multiresistant
      staphylococci, Enterobacteriaceae and Mycobacterium tuberculosis are already
      causing increased morbidity, mortality and huge costs in health budgets. New
      effective antibiotics will not be available for the next 10-15 years, since the
      pharmaceutical industry has lost interest in antibiotics. The major determinant
      in this field, in order to save the activity of the known antibiotics, is the
      control of antibiotic use.

PMID- 17521537
TI  - HIV/AIDS' spread and impact on other health-related millennium development goals-
      secondary publication.
AB  - HIV/AIDS threatens the development of countries with high HIV prevalence. This
      article focuses on the magnitude of the impact of HIV/AIDS on the millennium
      development goals (MDGs) for health. The article is based on a literature survey
      on the impact of HIV on child health, maternal mortality, tuberculosis (TB) and
      malaria. At global level 10% of child mortality is related to HIV/AIDS but the
      impact of HIV/AIDS on child mortality is much higher in high HIV prevalence
      countries being measured in the range of 27-42%. The impact on maternal mortality
      is difficult to estimate since the majority of pregnant women are not tested for
      HIV, but studies in a number of HIV high prevalence countries indicate an
      increasing negative impact on maternal mortality. The impact of HIV/AIDS on TB is
      significant. 9% of the TB cases are related to HIV/AIDS at the global level, but
      for the WHO African region alone, the impact of HIV/AIDS is estimated at 31%.
      There is evidence that HIV infections increase the risk for the progression of
      malaria in children and the risk of severe and complicated malaria in adults in
      stable malaria areas. However, the most evident effect of HIV on malaria is
      related to pregnant women. It is concluded that strategies to reach the MDGs for
      health must include a comprehensive and coordinated approach to fight the major
      health problems including a more suitable resource allocation and organisation of
      health services taking into account the many inter-linkages between diseases.

PMID- 17521538
TI  - Maternal death and the Millennium Development Goals.
AB  - Maternal health is one of the main global health challenges and reduction of the
      maternal mortality ratio, from the present 0.6 mio. per year, by three-quarters
      by 2015 is the target for the fifth Millennium Development Goal (MDG 5). However
      this goal is the one towards which the least progress has been made. There is not
      a simple and straight-forward intervention, which by itself will bring maternal
      mortality significantly down; and it is commonly agreed on that the high maternal
      mortality can only be addressed if the health system is strengthened. There is a
      common consensus about the importance of skilled attendance at delivery to
      address the high, maternal mortality. This consensus is also reflected in the MDG
      5, where the proportion of births attended by skilled health personnel is
      considered a key indicator. But even if countries invest massive efforts to
      increase skilled care, there will be a time lag. In addition, there is a need of
      major investment in human resources to counter the present momentum of emigration
      of qualified personnel from low income countries. To address the lack of skilled
      attendance, alternative strategies should therefore be developed and incorporated
      within the existing health system. One plausible solution could be to involve
      lower level providers such as community health workers to provide health facility
      based care under close supervision of authorized midwives. Upgrade of midlevel
      staff to provide life-saving obstetric surgery may also be an important
      innovative strategy. Along with the strategy of aiming at increasing the number
      of health facility based deliveries and the empowerment of non physicians to
      provide obstetric surgery, some preventive functions of basic care targeting
      women who prefer to deliver outside the health facilities should be developed.
      Finally, political leadership, openness to discuss women's rights, including
      abortion, and involving the community i.e. MDG 3 is essential to attain MDG 5.

PMID- 17521539
TI  - The economic impact of dengue hemorrhagic fever on family level in Southern
      Vietnam.
AB  - Dengue fever is a viral infection transmitted by mosquitoes (Aedes Aegypti). WHO
      estimates that 40% of the world's population live in areas endemic for dengue
      fever, and that there are approximately 50 million cases of dengue infection
      worldwide every year. This study aims to measure the economic consequences of
      dengue hemorrhagic fever in Southern Vietnam on family level. Estimating the
      economic impact of dengue fever/dengue hemorrhagic fever is important in order to
      prioritize resources for research, prevention, and control. So far no studies
      from Vietnam concerning this subject have been published. The study is based on
      standardized interviews. The study includes 175 children at the age 0-15 years,
      hospitalized in Children's Hospital No 1 in Ho Chi Minh City during a 10-week
      period in the fall of 2005. The children's parents/caretakers were interviewed on
      expenses related to the child's disease. The study shows that the average family
      cost of treating one child is approximately 61 USD including direct and indirect
      costs. On average, the largest expenses were those related to the initial visit
      at a local general practitioner, the hospital bill from Children's Hospital No1
      and lost income for the parents. Dengue hemorrhagic fever is a large expense for
      a family and can rightly be considered as a substantial socio-economic burden in
      Southern Vietnam. Larger studies are needed for a more accurate estimate of the
      extent of the expenses related to both dengue fever and dengue hemorrhagic fever.

PMID- 17521540
TI  - [Update in the clinical management of valvular heart disease].

PMID- 17521541
TI  - [The REGICOR registry and the epidemiology of myocardial infarction in Spain:
      forging a path].

PMID- 17521542
TI  - [Stem-cell therapy following large acute myocardial infarction].

PMID- 17521543
TI  - [Analysis of trends in myocardial infarction case-fatality, incidence and
      mortality rates in Girona, Spain, 1990-1999].
AB  - INTRODUCTION AND OBJECTIVES: The incidence of myocardial infarction in Spain is
      low, and mortality has been decreasing over the last few decades. The objective
      of this study was to analyze trends in myocardial infarction mortality,
      incidence, attack rates, and 28-day case-fatality attack rates between 1990 and
      1999 in the general population aged 35-74 years in Girona, Spain. METHODS: The
      study included all myocardial infarction cases in Girona classified according to
      the MONICA algorithm. Attack, incidence, mortality rates and case-fatality were
      calculated. In addition, the annual percentage change in each of these indicators
      during the study period was also calculated. RESULTS: The mean attack rate per
      100,000 inhabitants was 258 (95% CI, 249-267) in men and 55 (95% CI, 51-59) in
      women. The mean mortality rate per 100,000 was 99 (95% CI, 93-104) in men and 25
      (95% CI, 22-28) in women. Significant reductions in attack, incidence and
      recurrence rates were observed in men aged 35-64 years during the period 1990
      1999, but not in men aged 65-74 years, nor in women. CONCLUSIONS: Myocardial
      infarction incidence and mortality rates were low in the general population aged
      35-64 years. Rates improved in men aged 35-64 years during the period 1990-1999,
      but not in those aged 65-74 years, which indicates that a combination of primary
      and secondary prevention has increased the age at which a myocardial infarction
      or its recurrence is observed. Rates in woman were lower and did not change
      during the study period.

PMID- 17521544
TI  - [Regenerative therapy in patients with a revascularized acute anterior myocardial
      infarction and depressed ventricular function].
AB  - INTRODUCTION AND OBJECTIVES: It is difficult to distinguish the effects early
      revascularization and regenerative therapy have on left ventricular function in
      patients with acute myocardial infarction (AMI). This study was an investigation
      into three groups of patients who had a revascularized anterior wall AMI and
      depressed left ventricular function (i.e., ejection fraction < 45%). The aim was
      to compare changes in left ventricular function between patients who received
      regenerative therapy and those who did not. METHODS: Patients were randomly
      assigned to receive either an intracoronary infusion of autologous mononuclear
      bone marrow cells (Group I; n=10) or systemic administration of granulocyte
      colony-stimulating factor (G-CSF) (Group II; n=10), or to a control group (Group
      III; n=10). In Group I, intracoronary infusion was carried out 7(2) days after
      AMI. Group-II patients received a 10-day course of subcutaneous G-CSF injections,
      10 .g/kg per day starting 5 days after AMI. Ventricular function was assessed at
      baseline and 3-month follow-up. RESULTS: A 20% increase in mean ejection fraction
      was observed in Group I, compared with increases of 4% (P<.01) and 6% (P<.05) in
      Groups II and III, respectively. CONCLUSIONS: Intracoronary infusion of
      mononuclear bone marrow cells in patients with AMI and poor ventricular function
      was associated with better short-term functional recovery than previously
      reported. However, mobilization of stem cells by G-CSF did not have a significant
      influence on functional recovery.

PMID- 17521545
TI  - [Treatment with sildenafil, bosentan, or both in children and young people with
      idiopathic pulmonary arterial hypertension and Eisenmenger's syndrome].
AB  - INTRODUCTION AND OBJECTIVES: Pulmonary arterial hypertension carries a poor
      prognosis in both adult and pediatric patients. Current understanding of the
      mechanisms underlying pulmonary arterial hypertension has enabled the rapid
      development of appropriate drugs, such as endothelin receptor antagonists and 5
      phosphodieste-rase inhibitors, that can be administered orally and which are
      generally well tolerated. The aims of the present study were to evaluate
      functional class and exercise capacity following long-term treatment with
      sildenafil or bosentan in patients with idiopathic pulmonary arterial
      hypertension and Eisenmenger's syndrome and to compare results in the two groups.
      METHODS: Seven patients were included in the pulmonary arterial hypertension
      study, and diagnoses of idiopathic pulmonary arterial hypertension were
      confirmed. Five patients were treated with sildenafil, while two received
      bosentan. The five patients with a non-restrictive ventricular septal defect and
      pulmonary arterial hypertension were treated with sildenafil. In one patient,
      bosentan was added to the sildenafil. RESULTS: Both sildenafil and bosentan
      significantly improved exercise capacity in patients with idiopathic pulmonary
      arterial hypertension. The treatment effect was less in those with Eisenmenger
      physiology. Although the improvement in World Health Organization functional
      class was greater in patients with idiopathic pulmonary arterial hypertension, it
      was significant in both groups. CONCLUSIONS: Long-term treatment with sildenafil
      and bosentan improved both exercise capacity and functional class in patients
      with idiopathic pulmonary arterial hypertension and in those with hypertension
      due to congenital heart disease. The changes were more marked in patients with
      idiopathic pulmonary arterial hypertension.

PMID- 17521546
TI  - [Galician study of heart failure in primary care (GALICAP Study)].
AB  - INTRODUCTION AND OBJECTIVES: Heart failure (HF) is an important public health
      concern. Our aim was to evaluate the characteristics of HF patients in Galicia,
      Spain. METHODS: This descriptive, cross-sectional, multicenter study involved 149
      primary care physicians and recorded the characteristics of 1195 patients
      diagnosed with HF. RESULTS: Some 48% of patients were male, and their mean age
      was 76 years, though women were older (P<.001). Disease history included
      hypertension in 82%, hyperlipidemia in 47%, diabetes in 31%, atrial fibrillation
      in 49%, valvular disease in 35%, and ischemic heart disease in 32%. Mean systolic
      and diastolic blood pressures were 131 mm Hg and 76 mm Hg, respectively. Pressure
      was controlled (</= 130/80 mm Hg) in 43% of patients. Overall, 67% underwent
      echocardiography, of whom 61% had preserved systolic function. Coronary
      angiography was performed in 47% of patients with ischemic heart disease, more
      frequently in males than females (P<.001). The most commonly prescribed drugs
      were diuretics (82%), angiotensin-converting enzyme (ACE) inhibitors (48%),
      angiotensin II receptor antagonists (29%), and beta-blockers (27%). Patients with
      depressed systolic function were more frequently prescribed beta-blockers
      (P<.001), ACE inhibitors (P<.01), and antialdosterones (P<.05). During the last
      year, 57% of patients had been admitted to hospital, of whom 45% were admitted
      for cardiovascular reasons. CONCLUSIONS: The most prevalent form of HF in Galicia
      was HF with preserved systolic function, which was mostly associated with high
      blood pressure due to poor control. In patients with ischemic heart disease, the
      use of coronary angiography was influenced by sex. Drug treatment was suboptimal.
      Intervention programs are required to improve care in these patients.

PMID- 17521547
TI  - [Previous restenosis as a prognostic indicator in new conventional stent
      implantation at a different location].
AB  - INTRODUCTION AND OBJECTIVES: The aim was to determine whether data on restenosis
      of a previous stent are useful for predicting outcome in patients who need to
      undergo a second conventional stent implantation at a different location because
      of coronary disease progression. METHODS: The study included 80 patients who,
      during 2000-2004, underwent a second conventional (i.e., not drug-eluting) stent
      implantation for de novo lesions at a different location to that of the previous
      stent. Major adverse cardiac events (MACE) were defined as death, non-fatal
      myocardial infarction, or the need for target lesion revascularization (TLR).
      RESULTS: One year after the second procedure, the cumulative incidence of MACE
      was significantly higher in patients who experienced significant restenosis of
      the previous stent than in those who did not (40.6% vs 12.5%, P=.004). Univariate
      predictors of MACE were: evidence of previous stent restenosis, previous
      myocardial infarction, and a small vessel (< or =2.75 mm). However, the only
      independent predictor (Cox regression) of a MACE was previous stent restenosis
      (hazard ratio 3.85, 95% confidence interval, 1.46-10.18; P=.007). At one year,
      the TLR rate was also higher in patients with previous stent restenosis (31.3% vs
      8.3%; P=.008), in those with small vessels, and in diabetics. Previous stent
      restenosis and a small vessel were independent predictors of TLR. CONCLUSIONS:
      Restenosis of a previous stent is a strong predictor of major adverse events in
      patients undergoing a second conventional stent implantation at a different
      location because of coronary disease progression.

PMID- 17521548
TI  - [Impact of implementing common guidelines at different care levels in a
      healthcare area on the improvement of atrial fibrillation treatment].
AB  - INTRODUCTION AND OBJECTIVES: Atrial fibrillation (AF) is treated in different
      settings by different specialists. The objective of the study was to analyze the
      impact of the implementation of a practice guideline about AF treatment common to
      the different levels of health attention on the adequacy of AF treatment and on
      corrective interventions. METHODS: The study was performed in two periods, before
      and after the implementation of a practice guideline common to all health care
      levels. In each period, patients with AF who consulted to any of the health care
      attention levels of a sanitary area were included. Data referring to treatment
      and compliance of guidelines before and after the visit were recorded
      prospectively. RESULTS: 293 patients were included in the first period and 267 in
      the second one. After the guideline implementation, adequacy before the visit,
      both of antiarrythmic treatment and of antithrombotic prophylaxis were superior
      than in the first period (80% vs 71%, P=.009 and 81% vs 67%, P<.001,
      respectively). The percentage of improvement in case of a previous inadequacy of
      antithrombotic prophylaxis was significantly better in the second period than in
      the first one (35% vs 9%, P<.001), but the percentage of corrective interventions
      on antiarrhythmic treatment was similar in both periods. CONCLUSIONS: The
      implementation of a common practice guideline in the different levels of health
      care attention is useful to improve adequacy of AF treatment, although there is
      still some reluctance to change an inadequate antiarrythmic treatment.

PMID- 17521549
TI  - [Intermediate coronary care units: rationale, infrastructure, equipment, and
      referral criteria].
AB  - The Spanish Working Group on Coronary Artery Disease of Spanish Society of
      Cardiology has considered to be necessary the development of this document on the
      need, structure and organization of Intermediate Cardiac Care Units (ICCU). Acute
      coronary syndrome registries show that an important percentage of patients
      receive a suboptimal care, due to an inadequate management of health resources or
      absence of them. Intermediate cardiac care units arise to solve these challenges
      and to manage in an efficient way these expensive and limited resources. Their
      aims are: a) to provide each patient the level of care required; b) to optimize
      the structural, technical and human resources, and c) to make easier continuous
      care and care gradient. As a result, ICCU should be established as an essential
      part of the cardiology department aim to cardiac patients requiring monitoring
      and medical care superior to those available in a regular cardiac ward but whose
      risk does not justify the technical and human costs of a Coronary Unit. This
      document describes the structure (equipment, human resources, management)
      required to reach the goals previously reported and includes recommendations
      about indications of admission in a ICCU. These indications include: a) patients
      with NSTE-ACS with intermediate or high risk but hemodynamically stable, and b)
      low risk STEAMI or high risk STEAMI stabilized after an initial admission at the
      Coronary Unit. The admission of some patients undergoing invasive procedures or
      suffering non-coronary acute cardiac diseases, is also considered.

PMID- 17521550
TI  - [Sleep apnea-hypopnea syndromes and heart failure].
AB  - Heart failure (HF) and sleep-disordered breathing are conditions highly prevalent
      in the general population that often co-exist in the same patient.
      Epidemiological and pathophysiological studies indicate that there may be a
      causal link between sleep-disordered breathing and HF with either left
      ventricular systolic dysfunction or preserved ejection fraction. The presence of
      sleep-disordered breathing in HF patients expose the cardiovascular system to
      intermittent hypoxia, sympathetic activation, and increased preload and afterload
      and they trigger several inflammatory, oxidative and neurohumoral mechanisms that
      may precipitate the progression of the disease. Although there are no available
      data to indicate that treating sleep-disordered breathing in HF patients reduce
      cardiac mortality, several studies demonstrate a significant improvement in
      structural and functional cardiovascular parameters. This review focuses on the
      clinical and epidemiological bases, the pathophysiological mechanisms and the
      therapeutic implications between HF and sleep apnea-hypopnea syndromes.

PMID- 17521551
TI  - [Progress in the acute aortic syndrome].
AB  - Acute aortic syndrome is an acute lesion of the aortic wall involving the aortic
      media. The term covers aortic dissection, intramural hematoma, and penetrating
      ulcer. In the last few years, imaging techniques have increased our understanding
      of the natural history of these disease entities and of the dynamics of the
      disease processes. Despite significant advances in diagnosis and surgical
      treatment, the mortality rate in the acute phase remains high. Early clinical
      suspicion and greater surgical expertise appear to be the only factors that are
      able reduce mortality. Once the acute phase is past, the descending aorta
      continues to be involved in most patients, 30% of whom develop complications
      within 3-5 years. During this later phase, it is essential to optimize medical
      treatment and to use imaging techniques to follow-up the patient closely. The
      availability of endovascular treatment has provided new approaches to the
      management of the condition and could improve long-term prognosis. The aim of
      this article was to review recent progress in the diagnosis and therapeutic
      management of this syndrome.

PMID- 17521552
TI  - [Pacemaker implantation via a persistent left superior vena cava].

PMID- 17521553
TI  - [Post-infarction ventricular tachycardia with a QRS complex narrower than 140 ms:
      characterization and catheter ablation].
AB  - Typically, sustained monomorphic ventricular tachycardia (SMVT) in patients with
      a previous myocardial infarction (MI) is characterized by a wide QRS complex.
      However, occasionally patients present with SMVT and a narrow QRS complex (N
      SMVT). We studied retrospectively the incidence of N-SMVT (i.e., QRS interval
      <140 ms) in patients with a previous MI and inducible SMVT who underwent
      electrophysiological evaluation. Of the 135 consecutive patients with inducible
      SMVT, 8 (5.9%) presented with inducible N-SMVT. The mean QRS complex duration in
      patients with N-SMVT was 126 (8) ms. Radiofrequency ablation was successful in 5
      out of 6 patients (83%). One of the remaining two received an implantable
      defibrillator, while the other was given amiodarone. Findings during
      radiofrequency ablation showed that the reentry circuit was located in the left
      septum in 4 out of the 5 patients (80%). N-SMVT is relatively uncommon, but the
      success rate of radiofrequency ablation is high. The reentry circuit is most
      often located in the septum.

PMID- 17521554
TI  - [Patent ductus arteriosus closure using a new device: the Nit-Occlud device].
AB  - Between May 2003 and July 2006, we carried out percutaneous patent ductus
      arteriosus closure using a Nit-Occlud device in 28 patients, who had a median age
      of 1.8 years (range 0.5-21 years) and a median weight of 10.9 kg (range 5.9-64
      kg). The ductus arteriosus had several different morphologic forms, and there was
      one postsurgical recanalization of the ductus arteriosus. The median minimum
      ductal diameter was 1.8 mm and the median maximum aortic ampulla diameter was 6.5
      mm. The occlusion rate immediately after intervention was 53.5%, which increased
      to 95.2% by 12 months and to 100% by 18 months. The median follow-up time was
      20.5 months. The Nit-Occlud device provided an effective and safe means of patent
      ductus arteriosus closure, irrespective of ductus morphology.

PMID- 17521555
TI  - [Malignant ventricular arrhythmias as the initial manifestation of
      hyperthyroidism].

PMID- 17521556
TI  - [Ventricular tachycardia as initial presentation of pheochromocytoma].

PMID- 17521557
TI  - [Late cardiac perforation after percutaneous closure of an atrial septal defect
      using an amplatzer device].

PMID- 17521558
TI  - [Horemkenesi, da Vinci, Borodin: three forgotten pioneers in ischemic heart
      disease].

PMID- 17521559
TI  - Please release me.
AB  - In this issue of Neuron, Sudhof and colleagues determine which of the eight
      Ca(2+)-binding synaptotagmin isoforms expressed in brain can support synchronous
      neurotransmitter release at mammalian CNS synapses. Unexpectedly, only three
      synaptotagmin-1, -2, and -9-can serve as Ca(2+) sensors for fast transmission.
      Further characterization reveals the unique ability of each isoform to shape
      neurotransmission.

PMID- 17521560
TI  - NRG1 and synaptic function in the CNS.
AB  - Recent genetic evidence indicates that neuregulin 1 (NRG1) and its receptor erbB4
      may be susceptibility genes in schizophrenia, but their function in CNS synaptic
      transmission and circuitry is not well understood. In this issue of Neuron,
      studies from Li et al. and Woo et al. show that NRG1 and erbB4 regulate
      transmission at brain glutamate and GABA synapses. These findings raise the
      possibility of synaptic defects in schizophrenia.

PMID- 17521561
TI  - Defining the role of astrocytes in neuromodulation.
AB  - Astrocytes undergo elevations in intracellular calcium following activation of
      metabotropic receptors, which may trigger glutamate secretion and excitation of
      surrounding neurons. In this issue of Neuron, Fiacco et al. use transgenic mice
      that express a foreign G(q)-coupled receptor in astrocytes to show that selective
      stimulation of astrocytes is not sufficient to induce the release of glutamate.

PMID- 17521562
TI  - Is the movement representation in the motor cortex a moving target?
AB  - In redundant neural networks, many different combinations of connection weights
      will produce the same output, thereby providing many possible solutions for a
      given computation. In this issue of Neuron, Rokni et al. propose that the arm
      movement representations in the cerebral cortex act like redundant networks that
      drift randomly between different synaptic configurations with equivalent input
      output behavior because of random noise in the adaptive learning mechanism.

PMID- 17521563
TI  - Surfing on calcium waves.
AB  - A key question in brain development is how migration of neuronal precursors is
      guided to establish the ordered laminar layers. In the April 20, 2007 issue of
      Cell, Guan et al. show that the leading process of migrating cerebellar granule
      neurons senses repulsive Slit molecules by generating a Ca(2+) wave that
      propagates to the soma to cause reversal of cell polarity and migration.

PMID- 17521564
TI  - The sodium "leak" has finally been plugged.
AB  - Most electrophysiologists generally do not speak highly of leak currents. In
      reality, these conductances represent a crucial functional mechanism by which
      neurons control resting membrane potentials. A new study in Cell by Lu et al. has
      surprisingly confirmed the identity of the long-sought voltage-insensitive sodium
      leak conductance to be encoded by the third branch of the voltage-gated sodium
      and calcium channel family.

PMID- 17521565
TI  - A richness that cures.
AB  - A study in Nature by Fischer et al. shows that environmental enrichment or
      increasing histone acetylation rescue the ability to form new memories and re
      establish access to remote memories even in the presence of brain degeneration.
      Chromatin remodeling may be the final gate environmental enrichment opens to
      enhance plasticity and represents a promising target for therapeutical
      intervention in neurodegenerative diseases.

PMID- 17521566
TI  - The neurobiologist's guide to structural biology: a primer on why macromolecular
      structure matters and how to evaluate structural data.
AB  - Structural biology now plays a prominent role in addressing questions central to
      understanding how excitable cells function. Although interest in the insights
      gained from the definition and dissection of macromolecular anatomy is high, many
      neurobiologists remain unfamiliar with the methods employed. This primer aims to
      help neurobiologists understand approaches for probing macromolecular structure
      and where the limits and challenges remain. Using examples of macromolecules with
      neurobiological importance, the review covers X-ray crystallography, electron
      microscopy (EM), small-angle X-ray scattering (SAXS), and nuclear magnetic
      resonance (NMR) and biophysical methods with which these approaches are often
      paired: isothermal titration calorimetry (ITC), equilibrium analytical
      ultracentifugation, and molecular dynamics (MD).

PMID- 17521567
TI  - Remote control of neuronal activity with a light-gated glutamate receptor.
AB  - The ability to stimulate select neurons in isolated tissue and in living animals
      is important for investigating their role in circuits and behavior. We show that
      the engineered light-gated ionotropic glutamate receptor (LiGluR), when
      introduced into neurons, enables remote control of their activity. Trains of
      action potentials are optimally evoked and extinguished by 380 nm and 500 nm
      light, respectively, while intermediate wavelengths provide graded control over
      the amplitude of depolarization. Light pulses of 1-5 ms in duration at
      approximately 380 nm trigger precisely timed action potentials and EPSP-like
      responses or can evoke sustained depolarizations that persist for minutes in the
      dark until extinguished by a short pulse of approximately 500 nm light. When
      introduced into sensory neurons in zebrafish larvae, activation of LiGluR
      reversibly blocks the escape response to touch. Our studies show that LiGluR
      provides robust control over neuronal activity, enabling the dissection and
      manipulation of neural circuitry in vivo.

PMID- 17521568
TI  - Zfp423/OAZ participates in a developmental switch during olfactory neurogenesis.
AB  - The coordination of gene expression is critical for cell differentiation and the
      subsequent establishment of tissue function. We show here that a multiple zinc
      finger transcription factor, Zfp423/OAZ, is transiently expressed in newly
      differentiating olfactory-receptor neurons (ORNs) and has a key role in
      coordinating the expression of immature and mature stage-specific genes. OAZ
      deletion in mice impairs aspects of ORN differentiation, particularly the
      patterns of axonal projection to the olfactory bulb. OAZ gain-of-function
      experiments show that sustained OAZ expression throughout ORN maturation arrests
      ORN development at an immature stage and alters OR gene expression. Importantly,
      reintroducing OAZ expression in mature ORNs suppresses mature marker expression
      and reactivates immature-specific markers. Together, these experiments suggest
      that OAZ participates in a developmental switch regulating the transition from
      differentiation to maturation in ORNs.

PMID- 17521569
TI  - A critical period for enhanced synaptic plasticity in newly generated neurons of
      the adult brain.
AB  - Active adult neurogenesis occurs in discrete brain regions of all mammals and is
      widely regarded as a neuronal replacement mechanism. Whether adult-born neurons
      make unique contributions to brain functions is largely unknown. Here we
      systematically characterized synaptic plasticity of retrovirally labeled adult
      born dentate granule cells at different stages during their neuronal maturation.
      We identified a critical period between 1 and 1.5 months of the cell age when
      adult-born neurons exhibit enhanced long-term potentiation with increased
      potentiation amplitude and decreased induction threshold. Furthermore, such
      enhanced plasticity in adult-born neurons depends on developmentally regulated
      synaptic expression of NR2B-containing NMDA receptors. Our study demonstrates
      that adult-born neurons exhibit the same classic critical period plasticity as
      neurons in the developing nervous system. The transient nature of such enhanced
      plasticity may provide a fundamental mechanism allowing adult-born neurons within
      the critical period to serve as major mediators of experience-induced plasticity
      while maintaining stability of the mature circuitry.

PMID- 17521570
TI  - Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify
      distinct presynaptic properties in subsets of neurons.
AB  - Synaptotagmin-1 and -2 are known Ca(2+) sensors for fast synchronous
      neurotransmitter release, but the potential Ca(2+)-sensor functions of other
      synaptotagmins in release remain uncharacterized. We now show that besides
      synaptotagmin-1 and -2, only synaptotagmin-9 (also called synaptotagmin-5)
      mediates fast Ca(2+) triggering of release. Release induced by the three
      different synaptotagmin Ca(2+) sensors exhibits distinct kinetics and apparent
      Ca(2+) sensitivities, suggesting that the synaptotagmin isoform expressed by a
      neuron determines the release properties of its synapses. Conditional knockout
      mice producing GFP-tagged synaptotagmin-9 revealed that synaptotagmin-9 is
      primarily expressed in the limbic system and striatum. Acute deletion of
      synaptotagmin-9 in striatal neurons severely impaired fast synchronous release
      without changing the size of the readily-releasable vesicle pool. These data show
      that in mammalian brain, only synaptotagmin-1, -2, and -9 function as Ca(2+)
      sensors for fast release, and that these synaptotagmins are differentially
      expressed to confer distinct release properties onto synapses formed by defined
      subsets of neurons.

PMID- 17521571
TI  - The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and
      plasticity.
AB  - Neuregulin-1 (NRG1) signaling participates in numerous neurodevelopmental
      processes. Through linkage analysis, nrg1 has been associated with schizophrenia,
      although its pathophysiological role is not understood. The prevailing models of
      schizophrenia invoke hypofunction of the glutamatergic synapse and defects in
      early development of hippocampal-cortical circuitry. Here, we show that the erbB4
      receptor, as a postsynaptic target of NRG1, plays a key role in activity
      dependent maturation and plasticity of excitatory synaptic structure and
      function. Synaptic activity leads to the activation and recruitment of erbB4 into
      the synapse. Overexpressed erbB4 selectively enhances AMPA synaptic currents and
      increases dendritic spine size. Preventing NRG1/erbB4 signaling destabilizes
      synaptic AMPA receptors and leads to loss of synaptic NMDA currents and spines.
      Our results indicate that normal activity-driven glutamatergic synapse
      development is impaired by genetic deficits in NRG1/erbB4 signaling leading to
      glutamatergic hypofunction. These findings link proposed effectors in
      schizophrenia: NRG1/erbB4 signaling perturbation, neurodevelopmental deficit, and
      glutamatergic hypofunction.

PMID- 17521572
TI  - Neuregulin-1 enhances depolarization-induced GABA release.
AB  - Neuregulin-1 (NRG1), a regulator of neural development, has been shown to
      regulate neurotransmission at excitatory synapses. Although ErbB4, a key NRG1
      receptor, is expressed in glutamic acid decarboxylase (GAD)-positive neurons,
      little is known about its role in GABAergic transmission. We show that ErbB4 is
      localized at GABAergic terminals of the prefrontal cortex. Our data indicate a
      role of NRG1, both endogenous and exogenous, in regulation of GABAergic
      transmission. This effect was blocked by inhibition or mutation of ErbB4,
      suggesting the involvement of ErbB4. Together, these results indicate that NRG1
      regulates GABAergic transmission via presynaptic ErbB4 receptors, identifying a
      novel function of NRG1. Because both NRG1 and ErbB4 have emerged as
      susceptibility genes of schizophrenia, these observations may suggest a mechanism
      for abnormal GABAergic neurotransmission in this disorder.

PMID- 17521573
TI  - Selective stimulation of astrocyte calcium in situ does not affect neuronal
      excitatory synaptic activity.
AB  - Astrocytes are considered the third component of the synapse, responding to
      neurotransmitter release from synaptic terminals and releasing gliotransmitters-
      including glutamate--in a Ca(2+)-dependent manner to affect neuronal synaptic
      activity. Many studies reporting astrocyte-driven neuronal activity have evoked
      astrocyte Ca(2+) increases by application of endogenous ligands that directly
      activate neuronal receptors, making astrocyte contribution to neuronal effect(s)
      difficult to determine. We have made transgenic mice that express a Gq-coupled
      receptor only in astrocytes to evoke astrocyte Ca(2+) increases using an agonist
      that does not bind endogenous receptors in brain. By recording from CA1 pyramidal
      cells in acute hippocampal slices from these mice, we demonstrate that widespread
      Ca(2+) elevations in 80%-90% of stratum radiatum astrocytes do not increase
      neuronal Ca(2+), produce neuronal slow inward currents, or affect excitatory
      synaptic activity. Our findings call into question the developing consensus that
      Ca(2+)-dependent glutamate release by astrocytes directly affects neuronal
      synaptic activity in situ.

PMID- 17521574
TI  - Increased threshold for spike-timing-dependent plasticity is caused by unreliable
      calcium signaling in mice lacking fragile X gene FMR1.
AB  - Fragile X syndrome, caused by a mutation in the Fmr1 gene, is characterized by
      mental retardation. Several studies reported the absence of long-term
      potentiation (LTP) at neocortical synapses in Fmr1 knockout (FMR1-KO) mice, but
      underlying cellular mechanisms are unknown. We find that in the prefrontal cortex
      (PFC) of FMR1-KO mice, spike-timing-dependent LTP (tLTP) is not so much absent,
      but rather, the threshold for tLTP induction is increased. Calcium signaling in
      dendrites and spines is compromised. First, dendrites and spines more often fail
      to show calcium transients. Second, the activity of L-type calcium channels is
      absent in spines. tLTP could be restored by improving reliability and amplitude
      of calcium signaling by increasing neuronal activity. In FMR1-KO mice that were
      raised in enriched environments, tLTP was restored to WT levels. Our results show
      that mechanisms for synaptic plasticity are in place in the FMR1-KO mouse PFC,
      but require stronger neuronal activity to be triggered.

PMID- 17521575
TI  - Attention to surfaces modulates motion processing in extrastriate area MT.
AB  - In the visual system, early atomized representations are grouped into higher
      level entities through processes of perceptual organization. Here we present
      neurophysiological evidence that a representation of a simple object, a surface
      defined by color and motion, can be the unit of attentional selection at an early
      stage of visual processing. Monkeys were cued by the color of a fixation spot to
      attend to one of two transparent random-dot surfaces, one red and one green,
      which occupied the same region of space. Motion of the attended surface drove
      neurons in the middle temporal (MT) visual area more strongly than physically
      identical motion of the non-attended surface, even though both occurred within
      the spotlight of attention. Surface-based effects of attention persisted even
      without differential surface coloring, but attentional modulation was stronger
      with color. These results show that attention can select surface representations
      to modulate visual processing as early as cortical area MT.

PMID- 17521576
TI  - Motor learning with unstable neural representations.
AB  - It is often assumed that learning takes place by changing an otherwise stable
      neural representation. To test this assumption, we studied changes in the
      directional tuning of primate motor cortical neurons during reaching movements
      performed in familiar and novel environments. During the familiar task, tuning
      curves exhibited slow random drift. During learning of the novel task, random
      drift was accompanied by systematic shifts of tuning curves. Our analysis
      suggests that motor learning is based on a surprisingly unstable neural
      representation. To explain these results, we propose that motor cortex is a
      redundant neural network, i.e., any single behavior can be realized by multiple
      configurations of synaptic strengths. We further hypothesize that synaptic
      modifications underlying learning contain a random component, which causes
      wandering among synaptic configurations with equivalent behaviors but different
      neural representations. We use a simple model to explore the implications of
      these assumptions.

PMID- 17521577
TI  - The hyper IgE syndrome and mutations in TYK2.

PMID- 17521579
TI  - Human-hemato-lymphoid-system mice: opportunities and challenges.
AB  - With the recent advances in human-hemato-lymphoid-system mice, this commentary
      discusses the utility of these mice and further improvements required to generate
      an accessible system that allows predictive in vivo human hematology and
      immunology research.

PMID- 17521580
TI  - Unexpected steps in plasma-cell differentiation.
AB  - The transcriptional repressor Blimp-1 is considered the master regulator of
      plasma-cell differentiation. In this issue of Immunity, Kallies et al. (2007)
      identify a Blimp-1-independent stage of differentiation, followed by Blimp-1
      dependent terminal differentiation.

PMID- 17521581
TI  - A FAScinating receptor in self-tolerance.
AB  - In this issue of Immunity,Stranges et al. (2007) ablate expression of the death
      receptor Fas in T cells, B cells, and DC. Fas deficiency in any of these lineages
      is sufficient to break self-tolerance.

PMID- 17521582
TI  - T cells doing it for themselves: TGF-beta regulation of Th1 and Th17 cells.
AB  - The source of TGF-beta, which regulates inflammation in various disease settings,
      is unclear. In this issue of Immunity, Li et al. (2007) find that not only does T
      cell-produced TGF-beta regulate Th1-cell-mediated inflammation, but it is also
      required for the generation of Th17 cells in vivo.

PMID- 17521583
TI  - Good news, bad news for missing-self recognition by NK cells: autoimmune control
      but viral evasion.
AB  - In this issue of Immunity, Voigt et al. (2007) and Lu et al. (2007) extend the
      understanding of the consequences of missing-self recognition in immune evasion
      and immune cell regulation via NKRP-1 and CD94-NKG2A inhibitory receptors,
      respectively.

PMID- 17521584
TI  - Germinal-center B cells in the zone.
AB  - Visualization of lymphocyte dynamics in vivo has only recently become feasible.
      In this issue of Immunity, Hauser et al. (2007) gaze into the germinal-center
      reaction and find B cells making some unexpected moves.

PMID- 17521585
TI  - Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced
      survival of lymphoid-tissue-inducer cells.
AB  - Development of Peyer's patches and lymph nodes requires the interaction between
      CD4+ CD3- IL-7Ralpha+ lymphoid-tissue inducer (LTi) and VCAM-1+ organizer cells.
      Here we showed that by promoting their survival, enhanced expression of
      interleukin-7 (IL-7) in transgenic mice resulted in accumulation of LTi cells.
      With increased IL-7 availability, de novo formation of VCAM-1+ Peyer's patch
      anlagen occurred along the entire fetal gut resulting in a 5-fold increase in
      Peyer's patch numbers. IL-7 overexpression also led to formation of multiple
      organized ectopic lymph nodes and cecal patches. After immunization, ectopic
      lymph nodes developed normal T cell-dependent B cell responses and germinal
      centers. Mice overexpressing IL-7 but lacking either RORgamma, a factor required
      for LTi cell generation, or lymphotoxin alpha1beta2 had neither Peyer's patches
      nor ectopic lymph nodes. Therefore, by controlling LTi cell numbers, IL-7 can
      regulate the formation of both normal and ectopic lymphoid organs.

PMID- 17521586
TI  - Old habits die hard.

PMID- 17521587
TI  - Prophylaxis after tick bites.

PMID- 17521588
TI  - Single-dose prophylaxis against Lyme disease.

PMID- 17521589
TI  - Access to drugs: the case of Abbott in Thailand.

PMID- 17521590
TI  - A rotten end.

PMID- 17521591
TI  - Prevention and control of cystic echinococcosis.
AB  - Human cystic echinococcosis (hydatid disease) continues to be a substantial cause
      of morbidity and mortality in many parts of the world. Elimination is difficult
      to obtain and it is estimated that, using current control options, achieving such
      a goal will take around 20 years of sustained efforts. Since the introduction of
      current (and past) hydatid control campaigns, there have been clear technological
      improvements made in the diagnosis and treatment of human and animal cystic
      echinococcosis, the diagnosis of canine echinococcosis, and the genetic
      characterisation of strains and vaccination against Echinococcus granulosus in
      animals. Incorporation of these new measures could increase the efficiency of
      hydatid control programmes, potentially reducing the time required to achieve
      effective prevention of disease transmission to as little as 5-10 years.

PMID- 17521592
TI  - Immune reconstitution syndrome associated with opportunistic mycoses.
AB  - Host immunity is essential in facilitating the eradication of infection. However,
      immunological recovery and an imbalance characterised by either suboptimum or
      excessive expression of immune responses can also be harmful to the host.
      Inflammatory responses triggered by rapid resolution of immunosuppression can
      lead to a series of localised and systemic reactions, termed immune
      reconstitution syndrome (IRS), that are often misconstrued as failure of specific
      antifungal therapy to eliminate the offending fungal pathogen. Recognition of IRS
      has become increasingly relevant in the context of our current use of potent
      immunosuppressive agents and immunostimulators that allow rapid manipulation of
      the immune system. Whereas the conceptual principles of IRS underscore the
      adverse effects of an overzealous and dysregulated immune response, they also
      support a role of immunotherapies to augment immunity if induction of endogenous
      responses is inadequate for the control of infection.

PMID- 17521593
TI  - Clinical implications of HIV and hepatitis B co-infection in Asia and Africa.
AB  - Hepatitis B virus (HBV) is the leading cause of chronic liver disease and liver
      related death worldwide, with the majority of these cases occurring in areas of
      Africa and Asia where HBV prevalence is high. Many of the countries that are
      affected by hepatitis B are also affected by a high HIV burden, leading to
      frequent HIV/HBV co-infection. The consequences of co-infection, including
      increased liver-related morbidity and mortality, increased hepatitis B viral
      replication, immune reconstitution to HBV in the setting of antiretroviral
      therapy, and hepatotoxicity from antiretroviral drugs, are especially important
      in regions with expanding antiretroviral programmes. Little data, however, are
      available on HIV/HBV co-infection from regions with high chronic hepatitis B
      prevalence. This Review discusses the epidemiology, natural history,
      pathogenesis, and management of HIV/HBV co-infection from these areas. Topics for
      future research relevant to HIV/HBV co-infection in Africa and Asia are also
      highlighted.

PMID- 17521594
TI  - Should hepatitis B vaccination be introduced into childhood immunisation
      programmes in northern Europe?
AB  - Infection with hepatitis B causes between 500,000 and 1.2 million deaths per year
      worldwide, and is the leading cause of liver cancer. Over 12 years ago, WHO
      recommended that universal childhood hepatitis B vaccination be implemented
      globally. Despite this, Denmark, Finland, Iceland, Ireland, the Netherlands,
      Norway, Sweden, and the UK have yet to implement such a policy and instead
      currently adopt an "at-risk" strategy. Although all eight countries are classed
      as having low endemicity, factors such as increased travel and integration of
      immigrant communities are increasing the number of at-risk individuals in these
      countries. Considering the difficulty in identifying all at-risk individuals, and
      the lack of effectiveness of at-risk vaccination on reducing the overall
      incidence of hepatitis B, we recommend that these countries reassess their
      hepatitis B prevention strategies. Universal vaccination against hepatitis B is
      the only way to eliminate the major public-health impact of this disease.

PMID- 17521595
TI  - Trachoma: transmission, infection, and control.
AB  - Mass antibiotic treatment and facial cleanliness are central to WHO's strategy
      for the elimination of blindness caused by trachoma. Recent studies have
      highlighted the heterogeneous response of communities to mass treatment and the
      complex relation between infection with Chlamydia trachomatis and clinical
      disease. It is important to be able to explain these findings to predict and
      maximise the effect of treatment on active trachoma disease and blindness in the
      community. Here we review the immunobiology of trachoma and provide a simple
      conceptual model of disease pathogenesis. We show how incorporating this model
      into a mathematical framework leads to an explanation of the observed community
      distribution of infection, bacterial load, and disease with age. The predictions
      of the model and empirical data show some differences that underscore the
      importance of individual heterogeneity in response to infection. The implications
      of disease transmission and pathogenesis for trachoma control programmes are
      discussed.

PMID- 17521596
TI  - T-cell assays for the diagnosis of latent tuberculosis infection: moving the
      research agenda forward.
AB  - For nearly a century, the tuberculin skin test was the only tool available for
      the detection of latent tuberculosis infection. A recent breakthrough has been
      the development of T-cell-based interferon-gamma release assays. Current evidence
      suggests interferon-gamma release assays have higher specificity than the
      tuberculin skin test, better correlation with surrogate markers of exposure to
      Mycobacterium tuberculosis in low-incidence settings, and less cross-reactivity
      as a result of BCG vaccination compared with the tuberculin skin test. The body
      of literature supporting the use of interferon-gamma release assays has rapidly
      expanded. However, several unresolved and unexplained issues remain. To address
      these issues, a group of experts met in Geneva, Switzerland, in March, 2006, to
      discuss the research evidence on T-cell-based assays, their clinical usefulness,
      limitations, and directions for future research, with a specific focus on
      resource-limited and high HIV prevalence settings. On the basis of 2 days of
      discussions, a comprehensive research agenda was generated, which will propel the
      field forward by stimulating focused high-impact research and encourage the
      investment of resources needed to tackle priority research questions, especially
      in resource-limited settings. Ultimately, if adequately financed, the research
      findings will inform appropriate use of novel latent tuberculosis infection
      diagnostics in global tuberculosis control.

PMID- 17521597
TI  - The influence of advance information on the response complexity effect in manual
      aiming movements.
AB  - The relation between reaction time and the number of elements in a response has
      been shown to depend on whether simple or choice RT paradigms are employed. The
      purpose of the present study was to investigate whether advance information about
      the number of elements is the critical factor mediating the influence between
      reaction time and response elements. Participants performed aiming movements that
      varied in terms of the number of elements and movement amplitude. Prior to the
      stimulus, advance information was given about the number of elements and movement
      amplitude, movement amplitude only, number of elements only, or no information
      about the response. Reaction time and movement time to the first target increased
      as a function of number of elements only when the full response or the number of
      elements was specified in advance of the stimulus. The implication of these
      results for current models of motor programming and sequential control of aiming
      movements are discussed.

PMID- 17521598
TI  - A systematic approach to the development of fluorescent contrast agents for
      optical imaging of mouse cancer models.

PMID- 17521599
TI  - [Adenoid cystic carcinoma of the external auditory canal].
AB  - OBJECTIVES: To report a case of adenoid cystic carcinoma of the external auditory
      canal with petrous involvement. MATERIAL AND METHODS: A 50-year-old woman was
      referred to our department for the management of a necrotizing external otitis.
      Computed tomography and biopsy revealed an adenoid cystic carcinoma of the
      external auditory canal. RESULTS: The patient was treated by complete surgical
      excision. A radiation therapy completed the treatment. Follow-up time was 19
      months without evidence of recurrence. Adenoid cystic carcinoma of the external
      auditory canal is a rare tumor. It's a special type of carcinoma developing from
      the ceruminous glands. Histogenesis is difficult and unsettled. The most
      important survival factor is removal of the tumor with histologically free
      margins. CONCLUSIONS: Lack of specific clinical and radiological signs makes the
      diagnostic challenging. The adenoid cystic carcinoma is a rare neoplasm of the
      external auditory canal. An initial aggressive wide "en bloc" surgical resection
      is mandatory.

PMID- 17521600
TI  - [Bilateral vocal cords paralysis in newborn].
AB  - OBJECTIVE: This study aims at analyzing medical and surgical management as well
      as long-term follow-up of newborn (n=8) suffering from bilateral vocal cord
      paralysis. METHODS: This retrospective study reports information regarding
      pregnancy and birth history, family history, initial and delayed clinical
      features, treatment and follow-up of these infants. The following laryngeal
      procedures have been performed: Laser cordectomy (n=3), arytenoidopexy by
      external approach (n=2), botulinum toxin injection alone or associated with
      surgical treatments (n=6), enlargement laryngoplasty (n=1), endolaryngeal
      prostheses insertion (n=2). RESULTS: Any spontaneous recovery has been noticed.
      Four patients experiencing swallowing disorders required a gastrostomy in
      proportion to neurologic diseases and association of anomalies. Electromyograms
      performed were unremarkable. Botulinum toxin injected alone in laryngeal adductor
      muscles was not effective. The best results were observed when both
      arytenoidopexy and botulinum toxin injection were carried out. Bilateral
      cordectomies have been disappointing because of persistent vocal cord adduction.
      CONCLUSION: The low probability of spontaneous recovery and the drawbacks of
      tracheotomy encourage us to perform vocal cords adduction procedures as soon as
      possible.

PMID- 17521601
TI  - Effects of bedding systems selected by manual muscle testing on sleep and sleep
      related respiratory disturbances.
AB  - In this study, we investigated the feasibility of applying manual muscle testing
      (MMT) for bedding selection and examined the bedding effect on sleep. Four lay
      testers with limited training in MMT performed muscle tests for the selection of
      the bedding systems from five different mattresses and eight different pillows
      for 14 participants with mild sleep-related respiratory disturbances. For each
      participant individually, two bedding systems-one inducing stronger muscle forces
      and the other inducing weaker forces-were selected. The tester-participant pairs
      showed 85% and 100% agreement, respectively, for the selection of mattresses and
      pillows that induced the strongest muscle forces. The firmness of the mattress
      and the height of the pillow were significantly correlated with the body weight
      and body mass index of the participants for the selected strong bedding system
      but not for the weak bedding system. Finally, differences were observed between
      the strong and the weak bedding systems with regard to sleep-related respiratory
      disturbances and the percentage of slow-wave sleep. It was concluded that MMT can
      be performed by inexperienced testers for the selection of bedding systems.

PMID- 17521602
TI  - Folding and assembly of co-chaperonin heptamer probed by forster resonance energy
      transfer.
AB  - The ring-shaped heptameric co-chaperonin protein 10 (cpn10) is one of few
      oligomeric beta-sheet proteins that unfold and disassemble reversibly in vitro.
      Here, we labeled human mitochondrial cpn10 with donor and acceptor dyes to obtain
      FRET signals. Cpn10 mixed in a 1:1:5 ratio of donor:acceptor:unlabeled monomers
      form heptamers that are active in an in vitro functional assay. Monomer-monomer
      affinity, as well as thermal and chemical stability, of the labeled cpn10 is
      similar to the unlabeled protein, demonstrating that the labels do not perturb
      the system. Using changes in FRET, we then probed for the first time cpn10
      heptamer-monomer assembly/disassembly kinetics. Heptamer dissociation is very
      slow (1/k(diss) approximately 3h; 20 degrees C, pH 7) corresponding to an
      activation energy of approximately 50kJ/mol. Ring-ring mixing experiments reveal
      that cpn10 heptamer dissociation is rate limiting; subsequent associations events
      are faster. Kinetic inertness explains how cpn10 cycles on and off cpn60 as an
      intact heptamer in vivo.

PMID- 17521603
TI  - The application of synchrotron radiation induced X-ray emission in the
      measurement of zinc and lead in Wistar rat ameloblasts.
AB  - The development of analytical techniques for the measurement of trace elements in
      cellular compartments of developing teeth remains an important methodological
      issue in dental research. Recent advances in third generation synchrotron
      facilities have provided high brilliance X-ray sources that can be effectively
      used to study trace element distributions in small spatial regions with low
      detection limits. The present study describes for the first time the application
      of synchrotron radiation induced X-ray emission (SRIXE) in measuring the
      distribution of zinc and lead in the ameloblasts of developing Wistar rat teeth.
      Wistar rats were fed a standard rat diet, containing the normal dietary
      requirements of zinc, ad libitum and exposed to 100 ppm of lead in drinking
      water. Resin embedded sections of first mandibular molars were analysed using a
      13.3 keV incident monochromatic X-ray beam focussed to a 0.2 microm spot.
      Characteristic X-rays arising from the entire thickness of the sample were
      measured using an energy dispersive detector for quantitative analysis of
      elemental concentrations. The results showed that intranuclear concentrations of
      zinc were greater than levels in the cytoplasm. Furthermore, nuclear and
      cytoplasmic concentrations of zinc in the maturation stage (742+/-27 and 424+/-25
      ppm, respectively) were significantly higher than the zinc levels observed in the
      nucleus and cytoplasm of presecretory stage ameloblasts (132+/-10 and 109+/-10
      ppm, respectively) (p<0.05). A clear lead signal above the background was not
      detected in the ameloblasts and lead concentrations could only be reliably
      measured in the developing enamel. Overall, SRIXE was an effective method of
      studying the spatial distribution of zinc in the cells of developing teeth and
      offered a unique combination of sub-micron spatial resolution and parts-per
      million detection limits (0.8-1 and 0.6-1 ppm for zinc and lead, respectively).

PMID- 17521604
TI  - The effect of attentional focus on social anxiety.
AB  - The aim of the present study was to examine the effect of attentional focus on
      social anxiety in a group of high and low blushing-anxious subjects. One hundred
      and fourteen psychology undergraduate students were screened using the Fear of
      Blushing subscale of the Blushing Questionnaire [Bogels, S. M., & Reith, W.
      (1999). Validity of two questionnaires to assess social fears: The Dutch social
      phobia and anxiety questionnaire and the blushing, trembling and sweating
      questionnaire. Journal of Psychopathology and Behavioral Assessment, 21, 51-66].
      Those with the most extreme scores in the top and bottom 20% of the distribution
      were selected to form a high (n=22) and a low (n=22) blushing-anxious group.
      Subjects were randomly allocated to either a self-focused attention (SFA)
      condition or a task-focused attention (TFA) condition. They were asked to engage
      in a 5 min conversation with the first author, and were instructed to either self
      focus (SFA condition) or task-focus (TFA condition). Levels of social anxiety and
      self-awareness were measured using visual analogue scales. Results suggest that
      the there was a significant condition by group interaction, with high blushing
      individuals showing considerably higher levels of social anxiety in the SFA
      condition compared to the TFA condition while low blushing individuals showed no
      significant difference across the two conditions.

PMID- 17521605
TI  - Obsessive-compulsive disorder with comorbid major depression: what is the role of
      cognitive factors?
AB  - Individuals with obsessive-compulsive disorder (OCD) commonly experience comorbid
      mood disturbances such as major depressive disorder (MDD). Previous studies that
      have compared OCD patients with and without MDD have revealed differences in
      demographic characteristics, clinical severity, and symptom presentation between
      these two patient groups. Previous studies have not, however, examined whether
      there are differences with respect to cognitive processes. The present study
      therefore aimed to address this gap in the literature. Eighty patients with OCD
      and no unipolar mood disorders were compared with 34 OCD patients with comorbid
      major depression on measures of OCD symptoms, cognitions, and insight, as well as
      on measures of depression and functional impairment. Whereas depressed OCD
      patients evidenced higher scores than non-depressed OCD patients on semi
      idiographic measures of OCD symptoms and cognitions, this was not the case for
      nomothetic measures. Functional impairment and the tendency to misinterpret
      innocuous intrusive thoughts as significant emerged as unique predictors of
      depression within the entire sample of OCD patients. Results are discussed in
      terms of (a) the importance of semi-idiographic assessment of OCD, (b) possible
      explanations for the relationship between OCD symptoms, depression, and cognitive
      processes, and (c) the psychological treatment of comorbid OCD and MDD.

PMID- 17521606
TI  - Overproduction of OsSLRL2 alters the development of transgenic Arabidopsis
      plants.
AB  - SLR1 (SLENDER RICE 1) was thought to be the sole DELLA protein in rice
      considering the constitutive GA response phenotype of slr1 mutants. There were
      two other SLR1 homologous SLRL1 and SLRL2 (SLR1 like 1 and 2) which did not have
      DELLA domain but still shared high level similarity to the C-terminal region of
      SLR1 found after searching the whole rice genome. SLRL2 specially expressed in
      the embryo of immature rice seeds and the expression of SLRL2 was increased when
      treated with GA(3). The SLRL2 over-expressed transgenic Arabidopsis plants were
      semi-dwarfed, late flowering, and insensitive to GA. Moreover, the expression of
      AtGA20ox1 and AtGA3ox1 was increased and the expression of AtGA2ox1 decreased,
      indicating SLRL2 was a repressor of GA signaling. We suggested SLRL2 might
      function to overcome too strong GA responses and maintained a basic repression.
      Furthermore, a different form of DELLA family in monocots against dicots was
      discussed.

PMID- 17521607
TI  - Manipulation of reciprocal salt bridges at the heterodimerization interface
      alters the dimerization properties of mouse RXRalpha and PPARgamma1.
AB  - Heterodimerization with RXR is essential for the high-affinity specific binding
      of multiple nuclear receptors to their cognate DNA sequences. NR dimerization is
      a two-step process, initiated in solution by interaction between amino acid
      residues with helices 9 and 10 of the ligand binding domains of RXR and its NR
      partners. Studies of the orphan nuclear receptor HNF4alpha, which forms
      homodimers exclusively, have indicated that two charged residues in this region,
      HNF4alpha(K300) and HNF4alpha(E327), are key mediators of dimerization. We have
      analyzed the contribution of the homologous residues in RXRalpha (RXRalpha(E395),
      RXRalpha(K422)) and PPARgamma (PPARgamma(E405), PPARgamma(K432)) to the formation
      of the RXRalpha-PPARgamma heterodimer. Charge reversal mutants of RXRalpha
      (RXRalpha(E395K), RXRalpha(K422E)) and PPARgamma (PPARgamma(E405K),
      PPARgamma(K432E)) show impaired ability to form heterodimers with wild-type
      PPARgamma and RXRalpha, respectively. However, pairs of mutants with balanced
      charge changes, i.e., RXRalpha(E395K) with PPARgamma(K432E) and RXRalpha(K422E)
      with PPARgamma(E405K), are able to form dimers. Ligand response is preserved in
      the PPARgamma mutants, indicating the mutation does not result in major
      structural derangement of the protein. These results establish the importance of
      salt bridges between these residues in the heterodimerization of nuclear
      receptors, and offer a technical approach to generating functional NR mutants
      with directed heterodimerization specificity. Such mutants will be valuable tools
      in the genetic analysis of NR function.

PMID- 17521608
TI  - Retinoic acid-inducible G protein-coupled receptors bind to frizzled receptors
      and may activate non-canonical Wnt signaling.
AB  - Frizzled (Fz) seven-pass transmembrane receptors are Wnt receptors and function
      in a variety of developmental pathways. Here we identify retinoic acid-inducible
      gene-1, 2, 3, and 4 (RAIG1, 2, 3, and 4) as potential Fz binding proteins. RAIG
      proteins are seven-pass transmembrane receptors, and Xenopus RAIG2, 3, and 4 are
      expressed in early gastrula. XRAIG2 can activate small GTPases, such as RhoA,
      Rac, and Cdc42, and c-jun N-terminal kinase, thus exhibit activities that overlap
      with non-canonical Wnt/Fz signaling. Injection of XRAIG2 mRNA into Xenopus embryo
      causes a severe shortened and bent body axis due to defective gastrulation
      movements, reminiscent of abnormal non-canonical Wnt signaling. XRAIG2 affects
      convergent extension in activin-treated animal caps, which can be partially
      rescued by co-injection of a dominant-negative form of Cdc42. In zebrafish
      embryo, XRAIG2 also causes Ca(2+) flux, one of the consequences of non-canonical
      Wnt signaling. These results suggest a possible crosstalk/integration between
      Wnt/Frizzled and RAIG signal transduction pathways.

PMID- 17521609
TI  - Suppression of complement regulatory protein C1 inhibitor in vascular endothelial
      activation by inhibiting vascular cell adhesion molecule-1 action.
AB  - Increased expression of adhesion molecules by activated endothelium is a critical
      feature of vascular inflammation associated with the several diseases such as
      endotoxin shock and sepsis/septic shock. Our data demonstrated complement
      regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We
      hypothesized that C1INH has the ability of an anti-endothelial activation
      associated with suppression of expression of adhesion molecule(s). C1INH blocked
      leukocyte adhesion to endothelial cell monolayer in both static assay and flow
      conditions. In inflammatory condition, C1INH reduced vascular cell adhesion
      molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization
      and nuclear transcription level. Studies exploring the underlying mechanism of
      C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF
      kappaB activation and nuclear translocation in an IkappaBalpha-dependent manner.
      The inhibitory effects were associated with reduction of inhibitor IkappaB kinase
      activity and stabilization of the NF-kappaB inhibitor IkappaB. These findings
      indicate a novel role for C1INH in inhibition of vascular endothelial activation.
      These observations could provide the basis for new therapeutic application of
      C1INH to target inflammatory processes in different pathologic situations.

PMID- 17521610
TI  - Computational studies of the binding mechanism of calmodulin with chrysin.
AB  - Calmodulin (CaM) plays a crucial role in metabolism and physiology of eukaryotes
      by regulating biological activities. Multiple lines of evidences indicate that
      the phosphorylated flavonoids possess relatively stronger affinities for proteins
      by forming non-covalent complexes with them, and that the cellular functions are
      often triggered by this kind of interactions. Chrysin is one of the
      phosphorylated flavonoids that exist ubiquitously in plants and have remarkably
      beneficial pharmacological effects. In this study, the molecular docking tools
      were utilized to investigate the interactions of CaM with chrysin. Two different
      favorable binding modes have been observed. To complement the results obtained by
      the molecular docking study, an in-depth investigation into the binding modes was
      conducted with the molecular dynamics (MD) simulation to explore the binding
      profile and energy landscape. Based on the results thus obtained, a clear
      definition of the binding pocket for each of the two binding modes has been
      revealed. These findings may shed light upon the binding interactions of CaM with
      chrysin, providing a solid molecular basis for subset analysis of its
      pharmacological benefits.

PMID- 17521611
TI  - Characterization of transcriptional regulatory domains of ankyrin repeat cofactor
      1.
AB  - The ankyrin repeats cofactor-1 (ANCO-1) was recently identified as a p160
      coactivator-interacting protein that may inhibit transcriptional activity of
      nuclear receptors. Here, we have characterized the transcriptional regulatory
      domains of ANCO-1. Two intrinsic repression domains (RD) were identified: an N
      terminal RD1 at residues 318-611 and a C-terminal RD2 at 2369-2663. ANCO-1 also
      contains an activation domain (AD) capable of stimulating transcription in both
      mammalian and yeast cells. The minimal AD was delimited to a 70-amino acid region
      at residues 2076-2145. Overall, full-length ANCO-1 exhibited transcriptional
      repressor activity, suggesting that RD domains may suppress the AD activity. We
      further demonstrated that ANCO-1 silencing by siRNA enhanced progesterone
      receptor-mediated transcription. Together, these results indicate that the
      transcriptional potential of ANCO-1 may be modulated by a combination of
      repression and activation signals.

PMID- 17521612
TI  - Effect of exchange of amino acid residues of the surface region of the PST-01
      protease on its organic solvent-stability.
AB  - The PST-01 protease from an organic solvent tolerant Pseudomonas aeruginosa has
      high stability and activity in the presence of various organic solvents. The
      structure gene of the PST-01 protease was amplified by the error-prone PCR
      method. The mutated proteases were incubated in the presence of acetonitrile. By
      measuring remaining activities, two kinds of mutated PST-01 proteases of which
      the stabilities were changed were selected. These mutations hardly changed the
      profile of the activity and stability at various pHs. Their activity and
      stability at higher temperatures were slightly lower than those of the wild-type
      PST-01 protease. The stabilities of the mutated enzymes in the presence of
      various organic solvents were greatly reduced. In both the mutated PST-01
      proteases, amino acids located at the surface of the enzyme had been substituted.

PMID- 17521613
TI  - CXCR4 down-regulation by small interfering RNA inhibits invasion and tubule
      formation of human retinal microvascular endothelial cells.
AB  - The progressive alterations to the retinal microvasculature in diabetic
      retinopathy are known to cause vision loss. Chemokines are characterized by their
      ability to induce cell invasion, adhesion and migration. In this study, we used
      double siRNA transfection to transiently and selectively decrease the level of
      the endogenous CXCR4 in human retinal microvascular endothelial cells (HRMECs).
      The functional consequences of silencing CXCR4 expression in HRMECs were
      investigated using an endothelial cell migration assay and tubule formation in
      Matrigel. When CXCR4 expression was decreased with siRNA, HRMECs were less
      invasive and also resulted in markedly diminished vascular networks on Matrigel
      as compared to the controls. Additionally, hypoxia and VEGF, the factors
      affecting microvascular, regulate the expression level of CXCR4 in HRMECs,
      respectively, which have synergistic, additive effect in the HRMECs. As such,
      CXCR4 antagonists may become a therapeutic target for the treatment of retinal
      angiopathies.

PMID- 17521614
TI  - Adiponectin accelerates reverse cholesterol transport by increasing high density
      lipoprotein assembly in the liver.
AB  - Plasma high density lipoprotein (HDL)-cholesterol levels are negatively
      correlated with the incidence of coronary artery disease. HDL plays an important
      role in protecting against atherosclerosis by removing cholesterol from atheroma
      and transporting it back to the liver. The ATP-binding cassette transporters
      (ABCA1 and ABCG1) and scavenger receptor BI (SR-BI) are thought to be one of the
      rate-limiting factors to generate HDL in the liver. Adiponectin (APN) secreted
      from adipocytes is also one of the important molecules to inhibit the development
      of atherosclerosis. Recently, it has been reported that plasma HDL-cholesterol
      levels are positively correlated with plasma APN concentrations in humans.
      Therefore, we investigated the association of APN with HDL assembly in the liver.
      Human hepatoma cell line, HepG2 cells, were incubated for 24h in the culture
      medium with the indicated concentrations of recombinant APN. APN enhanced the
      mRNA level of apolipoprotein A-I (apoA-I) in HepG2 cells and increased the
      secretion of apoA-I from the cells to the medium. Furthermore, APN increased both
      mRNA and protein levels of ABCA1, but not ABCG1 and SR-BI, in HepG2 cells. Taken
      together, the current study demonstrates that APN might protect against
      atherosclerosis by increasing HDL assembly through enhancing ABCA1 pathway and
      apoA-1 synthesis in the liver.

PMID- 17521615
TI  - Characterization of two temperature-inducible promoters newly isolated from B.
      subtilis.
AB  - Here, two temperature sensitive promoters, P2 and P7, isolated from Bacillus
      subtilis, were characterized. The production of beta-galactosidase driven by
      these promoters was much higher at 45 degrees C than that at 37 degrees C both in
      Escherichia coli and B. subtilis and that the P2 promoter showed higher
      expression strength in B. subtilis at 45 degrees C. Thereby, an efficient
      temperature-inducible expression system was constructed by using P2 promoter in
      B. subtilis. Thus, we isolated and characterized a newly temperature inducible
      promoter and exploited it as a potential expression element in B. subtilis.

PMID- 17521616
TI  - Hypoxia enhances proliferation and tissue formation of human mesenchymal stem
      cells.
AB  - Changes in oxygen concentrations affect many of the innate characteristics of
      stem and progenitor cells. Human mesenchymal stem cells (hMSCs) were maintained
      under hypoxic atmospheres (2% O(2)) for up to seven in vitro passages. This
      resulted in approximately 30-fold higher hMSC expansion over 6 weeks without loss
      of multi-lineage differentiation capabilities. Under hypoxia, hMSCs maintained
      their growth-rates even after reaching confluence, resulting in the formation of
      multiple cell layers. Hypoxic hMSCs also displayed differences in the cell and
      nuclear morphologies as well as enhanced ECM formation and organization. These
      changes in cellular characteristics were accompanied by higher mRNA levels of Oct
      4 and HIF-2alpha, as well as increased expression levels of connexin-43, a
      protein used in gap junction formation. The results from this study demonstrated
      that oxygen concentrations affected many aspects of stem-cell physiology,
      including growth and in vitro development, and may be a critical parameter during
      expansion and differentiation.

PMID- 17521617
TI  - beta-Cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette
      transporters in macrophages.
AB  - Despite its serious adverse effects, recent accumulating evidence suggests that a
      physiological retinoic acid receptor (RAR) agonist, all-trans retinoic acid
      (atRA), exhibits preventive effects on atherogenesis. Therefore, the present
      study was designed to explore novel natural RAR ligands with anti-atherogenic
      effects in order to identify and develop a drug without severe side effects.
      Among xanthophylls and carotenoids studied, beta-cryptoxanthin and lutein
      exhibited RAR ligand activity in yeast two-hybrid system that was found to be
      completely abolished by the RAR pan-antagonist LE540. Furthermore, these
      molecules can bind the RAR ligand-binding domain in the CoA-BAP system but not
      RXR ligand-binding domain. These results indicate that both beta-cryptoxanthin
      and lutein serve as ligands for RAR, but not RXR, although their binding affinity
      was three orders of magnitude lower than that of atRA. Additionally, when applied
      to macrophages, beta-cryptoxanthin indeed was found to induce the ATP-binding
      cassette transporter A1 (ABCA1) and ABCG1 mRNAs, which exert anti-atherosclerotic
      effects by preventing cholesteryl ester accumulation in macrophages. The
      induction of ABCA1 proteins by beta-cryptoxanthin as well as atRA was abrogated
      by LE540. In summary, beta-cryptoxanthin appears to be more an efficient
      provitamin A source than other carotenoids and xanthophylls including beta
      carotene, since beta-cryptoxanthin can act not only as a RAR agonist but also a
      source of vitamin A. Taking into account that the pharmacodynamics difference
      between beta-cryptoxanthin and atRA, beta-cryptoxanthin appears to exert
      beneficial effects on atherogenesis through RAR activation in the manner
      different from atRA.

PMID- 17521618
TI  - De novo ceramide biosynthesis is associated with resveratrol-induced inhibition
      of ornithine decarboxylase activity.
AB  - Previous studies could demonstrate, that the naturally occuring polyphenol
      resveratrol inhibits cell growth of colon carcinoma cells at least in part by
      inhibition of protooncogene ornithine decarboxylase (ODC). The objective of this
      study was to provide several lines of evidence suggesting that the induction of
      ceramide synthesis is involved in this regulatory mechanisms. Cell growth was
      determined by BrdU incorporation and crystal violet staining. Ceramide
      concentrations were detected by HPLC-coupled mass-spectrometry. Protein levels
      were examined by Western blot analysis. ODC activity was assayed radiometrically
      measuring [(14)CO(2)]-liberation. A dominant-negative PPARgamma mutant was
      transfected in Caco-2 cells to suppress PPARgamma-mediated functions.
      Antiproliferative effects of resveratrol closely correlate with a dose-dependent
      increase of endogenous ceramides (p<0.001). Compared to controls the cell
      permeable ceramide analogues C2- and C6-ceramide significantly inhibit ODC
      activity (p<0.001) in colorectal cancer cells. C6-ceramide further diminished
      protein levels of protooncogenes c-myc (p<0.05) and ODC (p<0.01), which is
      strictly related to the ability of ceramides to inhibit cell growth in a time-
      and dose-dependent manner. These results were further confirmed using inhibitors
      of sphingolipid metabolism, where only co-incubation with a serine
      palmitoyltransferase (SPT) inhibitor could significantly counteract resveratrol
      mediated actions. These data suggest that the induction of ceramide de novo
      biosynthesis but not hydrolysis of sphingomyelin is involved in resveratrol
      mediated inhibition of ODC. In contrast to the regulation of catabolic
      spermidine/spermine acetyltransferase by resveratrol, inhibitory effects on ODC
      occur PPARgamma-independently, indicating independent pathways of resveratrol
      action. Due to our findings resveratrol could show great chemopreventive and
      therapeutic potential in the treatment of colorectal cancers.

PMID- 17521619
TI  - Cholesterol as a determinant of cooperativity in the M2 muscarinic cholinergic
      receptor.
AB  - M2 muscarinic receptor extracted from Sf9 cells in cholate-NaCl differs from that
      extracted from porcine sarcolemma. The latter has been shown to exhibit an
      anomalous pattern in which the capacity for N-[3H]methylscopolamine (NMS) is only
      50% of that for [3H]quinuclidinylbenzilate (QNB), yet unlabeled NMS exhibits high
      affinity for all of the sites labeled by [3H]QNB. The effects can be explained in
      terms of cooperativity within a receptor that is at least tetravalent [Park PS,
      Sum CS, Pawagi AB, Wells JW. Cooperativity and oligomeric status of cardiac
      muscarinic cholinergic receptors. Biochemistry 2002;41:5588-604]. In contrast, M2
      receptor extracted from Sf9 membranes exhibited no shortfall in the capacity for
      [3H]NMS at either 30 or 4 degrees C, although there was a time-dependent
      inactivation during incubation with [3H]NMS at 30 degrees C; also, any
      discrepancies in the affinity of NMS were comparatively small. The level of
      cholesterol in Sf9 membranes was only 4% of that in sarcolemmal membranes, and it
      was increased to about 100% by means of cholesterol-methyl-beta-cyclodextrin. M2
      receptors extracted from treated Sf9 membranes were stable at 30 and 4 degrees C
      and resembled those from heart. Cholesterol induced a marked heterogeneity
      detected in the binding of both radioligands, including a shortfall in the
      apparent capacity for [3H]NMS, and there were significant discrepancies in the
      apparent affinity of NMS as estimated directly and via the inhibition of [3H]QNB.
      The data can be described quantitatively in terms of cooperative effects among
      six or more interacting sites. Cholesterol therefore appears to promote
      cooperativity in the binding of antagonists to the M2 muscarinic receptor.

PMID- 17521620
TI  - Beneficial synergistic effects of concurrent treatment with cilostazol and
      probucol against focal cerebral ischemic injury in rats.
AB  - In the present study, we assessed the beneficial synergistic effects of
      concurrent treatment with low doses of cilostazol and probucol against focal
      cerebral ischemic infarct in rats. The ischemic infarct induced by 2-h occlusion
      of middle cerebral artery (MCA) and 22-h reperfusion was significantly reduced in
      rat brain that received cilostazol (20 mg/kg) and probucol (30 mg/kg) twice
      together with prominent improvement of neurological function compared to the
      effect of cilostazol or probucol monotherapy. Increased myeloperoxidase activity,
      a marker of neutrophil infiltration, observed in the penumbral zone of vehicle
      treated brain was more significantly reduced by cilostazol plus probucol in
      combination. Increased superoxide-, nitrotyrosine (a marker of peroxynitrite)-,
      poly(ADP-ribose) [a marker for poly(ADP-ribose) polymerase activity]-, and
      cleaved caspase-3-positive cells (a proapoptotic marker) in the vehicle sample
      were significantly attenuated by the combination therapy, while individual
      treatment with low dose of cilostazol or probucol showed a marginal effect. Taken
      together, it is suggested that the neuroprotective potentials of combination
      therapy with low doses of cilostazol plus probucol may provide beneficial
      therapeutic intervention in reducing the focal cerebral ischemic infarct in rats.

PMID- 17521622
TI  - Monocyte chemoattractant protein-1 and atherosclerosis: is there room for an
      additional biomarker?
AB  - Atherosclerosis is an inflammatory disease in which several chemokines are
      implicated. The roles of these molecules extend from the recruitment of
      circulating inflammatory cells to the activation of inflammatory and pro
      thrombotic cascades, which ultimately leads to an atherosclerosis-related event.
      One of the most studied chemokines is monocyte chemoattractant protein-1 (CCL2),
      which has been strongly linked to atherosclerosis in both animal and human
      studies. The higher the expression of either the CCL2 gene or its receptor CCR-2,
      the higher the likelihood of developing atherosclerosis in genetically-modified
      animals. Conversely, the deletion of either CCL2 or its receptor is followed by a
      significant reduction in the development of atherosclerotic plaques. Studies in
      humans yield controversial results. Most of these studies linked the plasma CCL2
      concentration to the occurrence of atherosclerosis or related events; however,
      this relationship does not seem to be independent of the classical, known risk
      factors. Currently, there are no suitable analytical tools to reach strong
      conclusions with respect to the value of plasma CCL2 concentration as a biomarker
      of atherosclerosis, but experimental evidence suggests that the CCL2/CCR2 pathway
      should be further explored as a diagnostic, prognostic and therapeutic target.

PMID- 17521621
TI  - TLR2 synergizes with both TLR4 and TLR9 for induction of the MyD88-dependent
      splenic cytokine and chemokine response to Streptococcus pneumoniae.
AB  - We previously demonstrated that induction of splenic cytokine and chemokine
      secretion in response to Streptococcus pneumoniae (Pn) is MyD88-, but not
      critically TLR2-dependent, suggesting a role for additional TLRs. In this study,
      we investigated the role of TLR2, TLR4, and/or TLR9 in mediating this response.
      We show that a single deficiency in TLR2, TLR4, or TLR9 has only modest,
      selective effects on cytokine and chemokine secretion, whereas substantial
      defects were observed in TLR2(-/-)xTLR9(-/-) and TLR2(-/-)xTLR4(-/-) mice, though
      not as severe as in MyD88(-/-) mice. Chloroquine, which inhibits the function of
      intracellular TLRs, including TLR9, completely abrogated detectable cytokine and
      chemokine release in spleen cells from TLR2(-/-)xTLR4(-/-) mice, similar to what
      is observed for mice deficient in MyD88. These data demonstrate significant
      synergy between TLR2 and both TLR4 and TLR9 for induction of the MyD88-dependent
      splenic cytokine and chemokine response to Pn.

PMID- 17521623
TI  - Quantitative flow cytometric analysis of transferrin receptor expression on
      reticulocytes.
AB  - BACKGROUND: A quantitative flow cytometric (FCM) method for transferrin receptor
      (TfR) expression on reticulocytes was developed and the results were compared
      with the markers of iron status. METHODS: A quantitative FCM analysis was
      performed using the Quantum Simply Cellular kit, according to which the antibody
      binding capacity (ABC) of TfR expression on reticulocytes was measured using a
      monoclonal antibody (CD71). Thiazole orange dye was used to identify
      reticulocytes. The proportion of TfR positive reticulocytes (%TfR(+)Ret) of all
      reticulocytes was also analyzed. The population consisted of 46 patients and 12
      controls. Patients were categorized (based on Advia 120 cellular indices and
      serum iron status parameters) as having replete iron status, functional iron
      deficiency (FID), and as FID combined with depletion of iron stores (FID+ID).
      RESULTS: The TfR expression (ABC values) were higher in FID (1763+/-922, p<0.001)
      and FID+ID (1441+/-727, p=0.05) groups in comparison with the controls (663+/
      110). Also, the %TfR(+)Rets were significantly higher in iron deficiency states
      than in controls. CONCLUSIONS: The quantitative FCM method for TfR expression on
      reticulocytes was found to reflect iron status at the cellular level. The
      potential usefulness of this method should be evaluated further in larger and
      more defined study populations.

PMID- 17521624
TI  - Postsynaptic neuroligin enhances presynaptic inputs at neuronal nicotinic
      synapses.
AB  - Neuroligins are cell adhesion molecules that interact with neurexins on adjacent
      cells to promote glutamatergic and GABAergic synapse formation in culture. We
      show here that neuroligin enhances nicotinic synapses on neurons in culture,
      increasing synaptic input. When neuroligin is overexpressed in neurons, the
      extracellular domain induces presynaptic specializations in adjacent cholinergic
      neurons as visualized by SV2 puncta. The intracellular domain is required to
      translate the SV2 puncta into synaptic input as reflected by increases in the
      frequency of spontaneous mini-synaptic currents. The PDZ-binding motif of
      neuroligin is not needed for these effects. Together, the extracellular and
      proximal intracellular domains of neuroligin are sufficient to induce presynaptic
      specializations, align them over postsynaptic receptor clusters, and increase
      synaptic function. Manipulation of endogenous neuroligin with beta-neurexin
      expressing cells confirms its presence; repressing function with dominant
      negative constructs and inhibitory shRNA shows that endogenous neuroligin helps
      confer functionality on existing nicotinic synaptic contacts. Endogenous
      neuroligin does not appear to be required, however, for initial formation of the
      contacts, suggesting that other components under these conditions can also
      initiate synapse formation. The results indicate that postsynaptic neuroligin is
      important for functional nicotinic synapses on neurons and that the effects
      achieved will likely depend on neuroligin levels.

PMID- 17521626
TI  - Preventive and curative effect of edaravone on nerve functions and oxidative
      stress in experimental diabetic neuropathy.
AB  - Oxidative stress is implicated as a final common pathway in the development of
      diabetic neuropathy and pharmacological interventions targeted at inhibiting free
      radical production have shown beneficial effects. In the present study, we have
      investigated the effects of edaravone (3 mg/kg; 3-Methyl-1-phenyl-2-pyrazolin-5
      one), a free radical scavenger (relatively selective to hydroxyl radicals) in
      streptozotocin (50 mg/kg i.p.) induced diabetic neuropathy in male Sprague-Dawley
      rats. Significant reduction (18%) in motor nerve conduction velocity, nerve blood
      flow (55%) and tail flick latency in cold (53%) and hot (50%) immersion test was
      observed in diabetic rats compared to age matched non-diabetic rats. Preventive
      (8 week) and curative (2 week) treatment of edaravone significantly improved the
      nerve conduction velocity and nociception but not nerve blood flow in diabetic
      rats. The changes in lipid peroxidation status and anti-oxidant enzymes
      (Superoxide dismutase and Catalase) levels observed in diabetic rats were
      significantly restored by edaravone treatment. Increase in blood pressure and
      vascular resistance was also significantly attenuated by edaravone treatment.
      This study provides experimental evidence to preventive and curative effect of
      edaravone on nerve function and oxidative stress in animal model of diabetic
      neuropathy. Hence edaravone may be tried clinically for the treatment of diabetic
      neuropathy since it is clinically used in stroke patients.

PMID- 17521625
TI  - Xenopus Bicaudal-C is required for the differentiation of the amphibian
      pronephros.
AB  - The RNA-binding molecule Bicaudal-C regulates embryonic development in Drosophila
      and Xenopus. Interestingly, mouse mutants of Bicaudal-C do not show early
      patterning defects, but instead develop polycystic kidney disease (PKD). To
      further investigate the molecular mechanism of Bicaudal-C in kidney development,
      we analyzed its function in the developing amphibian pronephros. Bicaudal-C mRNA
      was present in the epithelial structures of the Xenopus pronephros, the tubules
      and the duct, but not the glomus. Inhibition of the translation of endogenous
      Bicaudal-C with antisense morpholino oligomers (xBic-C-MO) led to a PKD-like
      phenotype in Xenopus. Embryos lacking Bicaudal-C developed generalized edemas and
      dilated pronephric tubules and ducts. This phenotype was caused by impaired
      differentiation of the pronephros. Molecular markers specifically expressed in
      the late distal tubule were absent in xBic-C-MO-injected embryos. Furthermore,
      Bicaudal-C was not required for primary cilia formation, an important organelle
      affected in PKD. These data support the idea that Bicaudal-C functions downstream
      or parallel of a cilia-regulated signaling pathway. This pathway is required for
      terminal differentiation of the late distal tubule of the Xenopus pronephros and
      regulates renal epithelial cell differentiation, which--when disrupted--results
      in PKD.

PMID- 17521627
TI  - Diabetes induced by partial hepatic sensory denervation in conscious rabbits.
AB  - Exposure of the anterior hepatic plexus to 2% perineurial capsaicin solution over
      three days caused transient insulin resistance confirmed by hyperinsulinaemic
      euglycaemic glucose clamping. Three additional perineurial capsaicin treatments
      divided by 3-month intervals yielded diabetes characterized by an increase in
      fasting blood glucose and glycated haemoglobin levels. Both insulin sensitivity
      and glycated haemoglobin level re-normalized over an additional 6-month period.
      We conclude that chronic partial hepatic sensory denervation produces diabetes in
      rabbits.

PMID- 17521628
TI  - Rapid induction of IAP family proteins and Smac/DIABLO expression after
      proapoptotic stimulation with doxorubicin in RPMI 8226 multiple myeloma cells.
AB  - We studied the expression dynamics of inhibitor of apoptosis protein (IAP) family
      members and Smac/DIABLO after treatment with doxorubicin in human multiple
      myeloma cell line RPMI 8226 and its doxorubicin-resistant variant DRR.
      Proapoptotic stimulation with doxorubicin rapidly induced the overexpression of
      mRNA as well as protein for IAPs in RPMI 8226 cells followed by a gradual
      decrease of their expression. Smac/DIABLO, which is known to neutralize IAPs,
      showed increased expression at the mRNA level after treatment; however, Western
      blot analysis revealed a slight decrease of the amount of protein.
      Immunoprecipitation analysis revealed the association of Smac/DIABLO with cIAP1
      or XIAP after treatment with doxorubicin. In contrast to the RPMI 8226 cells, DRR
      cells did not undergo apoptosis in response to doxorubicin treatment. The DRR
      cells had higher levels of IAPs expression at the mRNA level and did not show a
      remarkable peak or decrease in the expression of mRNAs for cIAP1, cIAP2, XIAP,
      and survivin after treatment with doxorubicin. Furthermore, the expression of
      Smac/DIABLO mRNA was not up-regulated after treatment. These findings indicate
      that the suppression of IAPs expression by Smac/DIABLO shortly after proapoptotic
      stimulation might play a role in the mechanisms of apoptotic induction, and that
      the maintenance of high IAPs expression and low Smac/DIABLO expression after
      treatment might lead to the doxorubicin-resistance of multiple myeloma cells.

PMID- 17521629
TI  - Towards a molecular description of intermediate filament structure and assembly.
AB  - Intermediate filaments (IFs) represent one of the prominent cytoskeletal elements
      of metazoan cells. Their constituent proteins are coded by a multigene family,
      whose members are expressed in complex patterns that are controlled by
      developmental programs of differentiation. Hence, IF proteins found in epidermis
      differ significantly from those in muscle or neuronal tissues. Due to their
      fibrous nature, which stems from a fairly conserved central alpha-helical coiled
      coil rod domain, IF proteins have long resisted crystallization and thus
      determination of their atomic structure. Since they represent the primary
      structural elements that determine the shape of the nucleus and the cell more
      generally, a major challenge is to arrive at a more rational understanding of how
      their nanomechanical properties effect the stability and plasticity of cells and
      tissues. Here, we review recent structural results of the coiled-coil dimer,
      assembly intermediates and growing filaments that have been obtained by a hybrid
      methods approach involving a rigorous combination of X-ray crystallography, small
      angle X-ray scattering, cryo-electron tomography, computational analysis and
      molecular modeling.

PMID- 17521630
TI  - Vasoactive intestinal peptide antagonist treatment during mouse embryogenesis
      impairs social behavior and cognitive function of adult male offspring.
AB  - Vasoactive intestinal peptide (VIP) is a regulator of rodent embryogenesis during
      the period of neural tube closure. VIP enhanced growth in whole cultured mouse
      embryos; treatment with a VIP antagonist during embryogenesis inhibited growth
      and development. VIP antagonist treatment during embryogenesis also had permanent
      effects on adult brain chemistry and impaired social recognition behavior in
      adult male mice. The neurological deficits of autism appear to be initiated
      during neural tube closure and social behavior deficits are among the key
      characteristics of this disorder that is more common in males and is frequently
      accompanied by mental retardation. The current study examined the blockage of VIP
      during embryogenesis as a model for the behavioral deficits of autism. Treatment
      of pregnant mice with a VIP antagonist during embryonic days 8 through 10 had no
      apparent effect on the general health or sensory or motor capabilities of adult
      offspring. However, male offspring exhibited reduced sociability in the social
      approach task and deficits in cognitive function, as assessed through cued and
      contextual fear conditioning. Female offspring did not show these deficiencies.
      These results suggest that this paradigm has usefulness as a mouse model for
      aspects of autism as it selectively impairs male offspring who exhibit the
      reduced social behavior and cognitive dysfunction seen in autism. Furthermore,
      the study indicates that the foundations of some aspects of social behavior are
      laid down early in mouse embryogenesis, are regulated in a sex specific manner
      and that interference with embryonic regulators such as VIP can have permanent
      effects on adult social behavior.

PMID- 17521631
TI  - Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal
      degeneration, and improve cerebral blood flow after experimental traumatic brain
      injury.
AB  - The treatment of traumatic brain injury (TBI) remains limited, and aside from
      surgical hematoma evacuation, clinical management is largely supportive and
      directed toward management of cerebral edema and intracranial hypertension.
      Secondary neuronal injury caused by ischemia and the development of cerebral
      edema may occur in the subacute phase, with intracranial pressures often peaking
      in the first several days following injury. Because inflammation contributes
      significantly to the pathophysiology of cerebral ischemia and endothelial
      dysfunction underlies the development of cerebral edema, therapeutic strategies
      that target the post-traumatic inflammatory cascade and reduce endothelial
      dysfunction hold enormous potential to improve clinical outcomes after TBI.
      Statins inhibit inflammation by suppressing inflammatory cytokine release, and by
      interfering with multiple steps of leukocyte recruitment and migration into the
      CNS. In this study, we demonstrate that treatment with atorvastatin and
      simvastatin markedly reduced functional neurological deficits after traumatic
      brain injury in mice. These effects were accompanied by histological reduction in
      degenerating hippocampal neurons and suppression of inflammatory cytokine mRNA
      expression in brain parenchyma. Furthermore, statin treatment improved cerebral
      hemodynamics following head injury. Thus, the administration of statins may
      represent a viable therapeutic strategy in the acute treatment of closed head
      injury.

PMID- 17521632
TI  - Trypanosoma cruzi: treatment with the iron chelator desferrioxamine reduces
      parasitemia and mortality in experimentally infected mice.
AB  - The effects of prolonged treatment with iron chelator (desferrioxamine) on the
      development of infection in mice inoculated with Y Trypanosoma cruzi were
      determined. Infected/treated mice presented lower levels of parasitemia and
      reduced mortality rate compared with infected/non-treated animals. The five out
      of twenty infected/treated mice that survived the acute phase of infection showed
      negative hemoculture and positive ELISA in the acute and chronic phases and
      positive PCR in the acute phase: in the chronic phase, three of the animals
      presented negative PCR. The single surviving infected/non-treated animal
      exhibited positive hemoculture, PCR and ELISA in both phases of infection.
      Infected groups presented lower levels of iron in the liver compared with
      treated/non-infected or non-treated/non-infected animals. The serum iron levels
      of the infected/non-treated group were higher on the 21st day post-infection in
      comparison with control and infected/treated groups. These results suggest that
      decrease of iron in the host leads to T. cruzi infection attenuation.

PMID- 17521634
TI  - DNA photodamage recognition by RNA polymerase II.
AB  - During gene transcription, RNA polymerase (Pol) II encounters obstacles,
      including lesions in the DNA template. Here, we review a recent structure
      function analysis of Pol II transcribing DNA with a bulky photo-lesion in the
      template strand. The study provided the molecular basis for recognition of a
      damaged DNA by Pol II, which is the first step in transcription-coupled DNA
      repair (TCR). The results have general implications for damage recognition and
      the TCR mechanism.

PMID- 17521633
TI  - Characterization of zinc finger protein 496 that interacts with Jumonji/Jarid2.
AB  - Jumonij (JMJ)/Jarid2 plays important roles in embryonic development and functions
      as a transcriptional repressor. Using yeast two-hybrid screening, we have
      identified a cofactor of JMJ, the zinc finger protein 496 (Zfp496) that contains
      a SCAN, KRAB and zinc finger domain. Our molecular analyses indicate that Zfp496
      functions as a transcriptional activator. Further, Zfp496 inhibits the
      transcriptional repression of JMJ and JMJ represses the transcriptional
      activation of Zfp496. This study demonstrates that JMJ physically and
      functionally interacts with Zfp496, which will provide important insights into
      endogenous target gene regulation by both factors.

PMID- 17521635
TI  - The Ndc80 complex: hub of kinetochore activity.
AB  - Kinetochores are protein scaffolds coordinating the process of chromosome
      segregation in mitosis. Kinetochore components are organized in functionally and
      topologically distinct domains that are designed to connect the sister chromatids
      to the mitotic spindle. The inner kinetochore proteins are in direct contact with
      the centromeric DNA, whilst the outer kinetochore proteins are responsible for
      binding to spindle microtubules. The conserved Ndc80 complex is implicated in
      several essential outer kinetochore functions, including microtubule binding and
      control of a safety device known as the spindle assembly checkpoint. Here, we
      describe how current work is contributing to unravel the complex endeavors of
      this essential kinetochore complex.

PMID- 17521636
TI  - Tapeworm infestation: a cause of iron deficiency anemia shown by capsule
      endoscopy.

PMID- 17521637
TI  - Repair of a polypectomy-induced duodenal perforation with a combination of
      hemoclip and band ligation.

PMID- 17521638
TI  - Rubber-sleeving a forceps for endoscopic removal of a flat, metallic foreign
      body.

PMID- 17521639
TI  - Rare gastric metastasis of testicular choriocarcinoma.

PMID- 17521640
TI  - Occlusion of metallic biliary stent related to nickel allergy.

PMID- 17521641
TI  - EUS-guided FNA facilitates the diagnosis of retroperitoneal endometriosis.

PMID- 17521642
TI  - Successful endoscopic treatment of Bouveret's syndrome with intracorporeal
      electrohydraulic lithotripsy.

PMID- 17521643
TI  - Dilation of a severe pancreatic stricture by using a guidewire left in place for
      24 hours.

PMID- 17521644
TI  - Simultaneous gastroscopy and colonoscopy for the diagnosis of gastrojejunocolic
      fistula.

PMID- 17521645
TI  - Video capsule endoscopy detection of jejunal carcinoid in life-threatening
      hemorrhage, first trimester pregnancy.

PMID- 17521646
TI  - Rapid colonoscopic detection and quantification of colonic ischemia by using a
      laser Doppler flowmeter.

PMID- 17521647
TI  - Endoscopic management of biliopleural fistula and biloma after percutaneous
      radiofrequency ablation of liver metastasis.

PMID- 17521648
TI  - In vivo histopathology of lymphocytic colitis.

PMID- 17521649
TI  - De novo stent-stone complex after long-term biliary stent placement:
      pathogenesis, diagnosis, and endotherapy.
AB  - BACKGROUND: Long-term and permanent biliary stenting have been reported in many
      studies and are infrequently practiced in selected patients with irretrievable
      common bile duct stones and biliary strictures. PATIENTS: Here we report 3 new
      cases and review 7 other cases of de novo stent-stone complex formation after
      long-term biliary stent placement. INTERVENTIONS: De novo stent-stone complexes
      developed in 3 young patients after unintended long-term biliary stent placement
      of 4.5 to 11 years' duration. The stent-stone complexes were successfully removed
      during ERCP with electrohydrolic lithotripsy (EHL) in combination with
      choledochoscopy or extracorporeal shock wave lithotripsy (ESWL) with mechanical
      lithotripsy (ML). RESULTS: The de novo radiolucent stones formed around and above
      the stent in the proximal and end part of the stent. The stones were generally
      large with a diameter>2 to 3 cm. The stent-stone complex usually assumed a 1
      sided dumbbell configuration inside the bile duct. The mean duration to clinical
      presentation after initial biliary stenting is 5.64 years (range 2-11 years).
      CONCLUSIONS: It is important to keep in mind that a biliary stent can act as a
      nidus for new biliary stone formation around the stent after long-term placement.
      We recommend that the optimal endotherapy in this situation is ML for the free
      floating complexes with short stents, and choledochoscopy with EHL or laser
      lithotripsy and ESWL for impacted complexes with longer stents.

PMID- 17521650
TI  - Glomus tumor of the ampulla.

PMID- 17521651
TI  - Chronic social stress in rainbow trout: does it promote physiological
      habituation?
AB  - The effect of chronic social stress on growth, energetic substrates and hormones
      was tested in rainbow trout, Oncorhynchus mykiss. After a 14-day isolation
      period, the fish were paired for 8 days. In order to expose fish to chronic
      intermittent social contact during pairing, they were maintained in direct
      contact with each other during the first day. After that, a black plastic screen
      partition was introduced in each tank, preventing direct contact between animals.
      Every day the partition was removed for 30 min, allowing physical interaction
      between fish. At the end of pairing period, they were isolated again for 13 days.
      Fish were weighed and blood was sampled frequently during the experiment. Plasma
      levels of cortisol, growth hormone, glucose, total protein and free amino acids
      were quantified. Both dominants and subordinates had specific growth rate
      decreased during the pairing period, but only subordinates increased when the
      stressor was abolished (dominants: 0.32+/-0.21 and 0.24+/-0.41, subordinates: 
      0.77+/-0.29 and 0.37+/-0.31, respectively). Dominants showed a higher cortisol
      level one week after pairing condition had been abolished than subordinates
      (dominants: 56.76+/-13.26, subordinates: 31.89+/-13.36). We conclude that chronic
      condition of intermittent social stress represents a stressful condition for
      animals of both hierarchical ranks and a treatment of one daily short direct
      contact between conspecifics does not promote habituation in fish, as mentioned
      for other stressors.

PMID- 17521652
TI  - Pattern recognition-based supervision of indirect adaptation for better
      disturbance handling.
AB  - An advanced pattern recognition-based supervision algorithm for an indirect
      adaptive controller is proposed. The aim is to improve performance under certain
      conditions that are common in the industrial environment, in which indirect
      adaptive controllers with simple supervision are known to perform poorly or
      unreliably. Specifically, the problem of large invasive unmeasured disturbances
      of short or longer duration is addressed. The supervisor is designed to recognize
      such events as quickly as possible by analysis of recent control signals, without
      additional measurements. It applies appropriate strategies to prevent model
      degradation by learning from misleading data and to maintain acceptable
      performance under unfavorable conditions. As an illustration, it has been applied
      to the control of a model of a semi-cleanroom HVAC installation subsystem.

PMID- 17521653
TI  - MIMO variable structure controller design for a bioreactor benchmark process.
AB  - In this paper, variable structure control of a bioreactor is studied. The process
      has two state variables named cell mass and nutrient amount, and two control
      inputs to maintain the state variables at their desired levels. Although the
      state space representation of the system seems simple, the system displays
      several challenges that make it necessary to develop a good flowrate (control)
      management strategy. Due to the plant-model mismatch, variable structure control
      technique is applied and it is seen that the sliding subspace is reached in
      finite time and the behavior thereafter is insensitive to considerable degrees of
      variation in the parameters and disturbances. The design is based on the nominal
      model and a comparison with a feedback linearizing controller is presented. The
      objective of the paper is to illustrate the efficacy of MIMO sliding mode control
      on a benchmark problem. Overall, the results with the proposed controller
      demonstrate the following desirable characteristics: (i) very good tracking
      precision (ii) small percent overshoot values and (iii) good decoupling of the
      process states.

PMID- 17521655
TI  - Investigating the endemic transmission of the hepatitis C virus.
AB  - The hepatitis C virus (HCV) infects at least 3% of people worldwide and is a
      leading global cause of liver disease. Although HCV spread epidemically during
      the 20th century, particularly by blood transfusion, it has clearly been present
      in human populations for several centuries. Here we attempt to redress the
      paucity of investigation into how long-term endemic transmission of HCV has been
      maintained. Such transmission not only represents the 'natural' route of
      infection but also contributes to new infections today. As a first step, we
      investigate the hypothesis that HCV can be mechanically transmitted by biting
      arthropods. Firstly, we use a combined bioinformatic and geographic approach to
      build a spatial database of endemic HCV infection and demonstrate that this can
      be used to geographically compare endemic HCV with the range distributions of
      potential vector species. Second, we use models from mathematical epidemiology to
      investigate if the parameters that describe the biting behaviour of vectors are
      consistent with a proposed basic reproduction number (R0) for HCV, and with the
      sustained transmission of the virus by mechanical transmission. Our analyses
      indicate that the mechanical transmission of HCV is plausible and that much
      further research into endemic HCV is needed.

PMID- 17521654
TI  - Nimbus (BgI): an active non-LTR retrotransposon of the Schistosoma mansoni snail
      host Biomphalaria glabrata.
AB  - The freshwater snail Biomphalaria glabrata is closely associated with the
      transmission of human schistosomiasis. An ecologically sound method has been
      proposed to control schistosomiasis using genetically modified snails to displace
      endemic, susceptible ones. To assess the viability of this form of biological
      control, studies towards understanding the molecular makeup of the snail relative
      to the presence of endogenous mobile genetic elements are being undertaken since
      they can be exploited for genetic transformation studies. We previously cloned a
      1.95kb BamHI fragment in B. glabrata (BGR2) with sequence similarity to the human
      long interspersed nuclear element (LINE or L1). A contiguous, full-length
      sequence corresponding to BGR2, hereafter-named nimbus (BgI), has been identified
      from a B. glabrata bacterial artificial chromosome (BAC) library. Sequence
      analysis of the 65,764bp BAC insert contained one full-length, complete nimbus
      (BgI) element (element I), two full-length elements (elements II and III)
      containing deletions and flanked by target site duplications and 10 truncated
      copies. The intact nimbus (BgI) contained two open-reading frames (ORFs 1 and 2)
      encoding the characteristic hallmark domains found in non-long terminal repeat
      retrotransposons belonging to the I-clade; a nucleic acid binding protein in ORF1
      and an apurinic/apyrimidinic endonuclease, reverse transcriptase and RNase H in
      ORF2. Phylogenetic analysis revealed that nimbus (BgI) is closely related to
      Drosophila (I factor), mosquito Aedes aegypti (MosquI) and chordate ascidian
      Ciona intestinalis (CiI) retrotransposons. Nimbus (BgI) represents the first
      complete mobile element characterised from a mollusk that appears to be
      transcriptionally active and is widely distributed in snails of the neotropics
      and the Old World.

PMID- 17521656
TI  - Plasmodium falciparum Pf34, a novel GPI-anchored rhoptry protein found in
      detergent-resistant microdomains.
AB  - Apicomplexan parasites are characterised by the presence of specialised
      organelles, such as rhoptries, located at the apical end of invasive forms that
      play an important role in invasion of the host cell and formation of the
      parasitophorous vacuole. In this study, we have characterised a novel Plasmodium
      falciparum rhoptry protein, Pf34, encoded by a single exon gene located on
      chromosome 4 and expressed as a 34kDa protein in mature asexual stage parasites.
      Pf34 is expressed later in the life cycle than the previously described rhoptry
      protein, Rhoptry Associated Membrane Antigen (RAMA). Orthologues of Pf34 are
      present in other Plasmodium species and a potential orthologue has also been
      identified in Toxoplasma gondii. Indirect immunofluorescence assays show that
      Pf34 is located at the merozoite apex and localises to the rhoptry neck. Pf34,
      previously demonstrated to be glycosyl-phosphatidyl-inositol (GPI)-anchored
      [Gilson, P.R., Nebl, T., Vukcevic, D., Moritz, R.L., Sargeant, T., Speed, T.P.,
      Schofield, L., Crabb, B.S. (2006) Identification and stoichiometry of GPI
      anchored membrane proteins of the human malaria parasite Plasmodium falciparum.
      Mol. Cell. Proteomics 5, 1286-1299.], is associated with parasite-derived
      detergent-resistant microdomains (DRMs). Pf34 is carried into the newly invaded
      ring, consistent with a role for Pf34 in the formation of the parasitophorous
      vacuole. Pf34 is exposed to the human immune system during infection and is
      recognised by human immune sera collected from residents of malaria endemic areas
      of Vietnam and Papua New Guinea.

PMID- 17521657
TI  - Muscle geometry affects accuracy of forearm volume determination by magnetic
      resonance imaging (MRI).
AB  - Upper extremity musculoskeletal modeling is becoming increasingly sophisticated,
      creating a growing need for subject-specific muscle size parameters. One method
      for determining subject-specific muscle volume is magnetic resonance imaging
      (MRI). The purpose of this study was to determine the validity of MRI-derived
      muscle volumes in the human forearm across a variety of muscle sizes and shapes.
      Seventeen cadaveric forearms were scanned using a fast-spoiled gradient echo
      pulse sequence with high isotropic spatial resolution (1mm(3) voxels) on a 3T MR
      system. Pronator teres (PT), extensor carpi radialis brevis (ECRB), extensor
      pollicis longus (EPL), flexor carpi ulnaris (FCU), and brachioradialis (BR)
      muscles were manually segmented allowing volume to be calculated. Forearms were
      then dissected, muscles isolated, and muscle masses obtained, which allowed
      computation of muscle volume. Intraclass correlation coefficients (ICC(2,1)) and
      absolute volume differences were used to compare measurement methods. There was
      excellent agreement between the anatomical and MRI-derived muscle volumes (ICC =
      0.97, relative error = 12.8%) when all 43 muscles were considered together. When
      individual muscles were considered, there was excellent agreement between
      measurement methods for PT (ICC = 0.97, relative error = 8.4%), ECRB (ICC = 0.93,
      relative error = 7.7%), and FCU (ICC = 0.91, relative error = 9.8%), and fair
      agreement for EPL (ICC = 0.68, relative error = 21.6%) and BR (ICC = 0.93,
      relative error = 17.2%). Thus, while MRI-based measurements of muscle volume
      produce relatively small errors in some muscles, muscles with high surface area
      to-volume ratios may predispose them to segmentation error, and, therefore, the
      accuracy of these measurements may be unacceptable.

PMID- 17521659
TI  - Analysis of diterpenoic compounds in natural resins applied as binders in museum
      objects by capillary electrophoresis.
AB  - The exudates of conifers consist mainly of diterpenoic acids of the abietane and
      pimarane type (abietic, neoabietic, dehydroabietic, palustric, pimaric,
      isopimaric, levopimaric and sandaracopimaric acid) and larixol acetate. These
      natural resins were used as adhesives, coatings, varnishes or plasticizers in
      artistic and historic works since ancient times. For the purpose of conservation
      and restoration and for art historic examination of such museum objects the
      identification of the binding media used is undoubtedly of paramount importance.
      In the present paper, the characterization of these resins based on the pattern
      of their diterpenoid constituents is carried out by capillary electrophoresis.
      For separation a background electrolyte which has been initially introduced for
      the analysis of chlorinated and natural resin acids in waste water was modified
      and the experimental conditions were adjusted in terms of resolution and analysis
      time. Separation was carried out in borate buffer at pH 9.25 (ionic strength 20
      mmol L(-1)) with methyl-beta-cyclodextrin and sulfobutylether-beta-cyclodextrin
      as additives to increase selectivity and enhance the solubility of the analytes.
      With this electrophoretic system the resin acids of interest and larixol acetate-
      all as anionic cyclodextrin complexes--were separated within 5 min and detected
      at 200, 250 and 270 nm with a diode array detector. The electrophoretic patterns
      served for the characterisation of the relevant diterpenoic resins, balsams and
      copals. Sample pre-treatment was limited to sonication in methanol at 55 degrees
      C for 30 min. This enables the identification of the resins in mixtures with
      other binders like plant gums, animal glues or drying oils, even when these media
      are present in excess. Colophony was identified as resinous constituent of a
      modelling mass for gilded frames originating from the 19th century.

PMID- 17521658
TI  - Evaluation of individual particle capillary electrophoresis experiments via
      quantile analysis.
AB  - The number of particles in a sample heavily influences the shape of a
      distribution corresponding to the individual particle measurements. Selecting an
      adequate number of particles that prevents biases due to sample size is
      particularly difficult for complex biological systems in which statistical
      distributions are not normal. Quantile analysis is a powerful statistical
      technique that can rapidly compare differences between multiple distributions of
      individual particles. This report utilizes quantile analysis to show that the
      number of events detected affects the mobility distributions for rat liver and
      mouse liver mitochondria, sample individual particles, when analyzed via
      capillary electrophoresis with laser-induced fluorescence. When the mitochondrial
      sample is small (e.g. <78), there are not enough events to obtain statistically
      relevant mobility data. Adsorption to the capillary surface also significantly
      affects the mobility distribution at a small number of events in uncoated and
      dynamically coated capillaries. These adsorption effects can be overcome when the
      mitochondrial load on the capillary is sufficiently large (i.e. >609 and >1426
      events for mouse liver on uncoated capillaries and rat liver on dynamically
      coated capillaries, respectively). It is anticipated that quantile analysis can
      be used to study other distributions of individual particles, such as
      nanoparticles, organelles, and biomolecules, and that distributions of these
      particles will also be dependent on sample size.

PMID- 17521660
TI  - Microextraction across supported liquid membranes forced by pH gradients and
      electrical fields.
AB  - The present work has for the first time compared extraction of basic analytes
      across a supported liquid membrane (SLM) based on (1) passive diffusion in a pH
      gradient sustained over the SLM and (2) electrokinetic migration in an electrical
      field sustained over the SLM. For the passive diffusion experiments, performed as
      liquid-phase microextraction (LPME), five basic drugs were extracted under strong
      agitation from alkaline samples (10mM NaOH), through 2-nitrophenyl octylether
      immobilized in the pores of a porous hollow fibre of polypropylene (SLM), and
      into 25 microl of 10mM HCl as the acceptor solution. The experiments based on
      electrokinetic migration, performed as electro membrane isolation (EMI), were
      conducted under strong agitation from acidic samples (10mM HCl), through the same
      SLM as in LPME, and into 25 microl of 10mM HCl as the acceptor solution. Whereas
      LPME relied on diffusion and to some extent also convection as the principal
      mechanisms of mass transfer, mass transfer in EMI also included a strong
      contribution from electrokinetic migration. Thus, extraction kinetics was
      improved by a factor between 6 and 17 utilizing EMI instead of LPME. This major
      difference in terms of speed was especially pronounced from small sample volumes
      (150 microl), and suggest that EMI may be a very interesting future concept for
      miniaturized sample preparation. In addition to improved extraction kinetics,
      extraction rates were strongly compound dependent in EMI, opening the possibility
      to control the extraction selectivity by the extraction time.

PMID- 17521661
TI  - Development of an ultra-performance liquid chromatography-mass spectrometry
      method for the detection of lipophilic marine toxins.
AB  - A rapid method for the detection of marine toxins was developed using an ultra
      performance liquid chromatography (UPLC) system coupled to a latest generation
      mass spectrometry (MS) system. The analysis of 21 lipophilic marine toxins was
      achieved on an Acquity C18 column using a water-acetonitrile gradient with a
      cycle time of 6.6 min, reducing analysis time by more than a factor two compared
      to HPLC while maintaining peak resolution. Linear ranges, limits of detection and
      limits of quantification were established for okadaic acid (OA), pectenotoxin-2,
      azaspiracid-1 (AZA1), yessotoxin, gymnodimine and 13-desmethylspirolide C. The
      method was found to be accurate when using a triplicate methanolic extraction.
      Matrix effects were assessed by standard addition of OA and AZA1 in extracts of
      raw and heat-treated flesh of mussels and oysters. For the analysis of AZA1, the
      UPLC-MS method was always prone to signal suppression, while for OA analysis
      signal suppression was observed in extracts of raw shellfish flesh and signal
      enhancement in extracts of heat-treated flesh. Matrix effects occurring in the
      method presented are diminished compared to previous studies.

PMID- 17521662
TI  - Detection of dideuterium in diprotium gas at infinitesimal concentration using a
      trace reduction detector.
AB  - An analyzer able to detect extremely small concentrations of dideuterium in
      diprotium gas was developed. To examine its performance, four gas samples of pure
      diprotium with dideuterium concentrations of 0.25, 0.5, 1, and 5 cm(3)/m(3) were
      measured using the analyzer, and peak areas and retention times from 18
      chromatograms were determined. Results indicated that the peaks were distributed
      within a relative standard deviation of approximately 15% and a linear
      correlation existed between peak area and concentration. Retention times were
      stable, showing a relative standard deviation of 1% with repeated tests and
      having no correlation with concentration of the four gas samples.

PMID- 17521663
TI  - Characterization of poly(ethylene imine) layers on mica by the streaming
      potential and particle deposition methods.
AB  - Deposition kinetics of polystyrene latex (averaged particle size of 0.66 microm)
      on mica covered by poly(ethylene imine) (PEI), a cationic polyelectrolyte having
      an average molecular mass of 75,000 g mol(-1), was studied using the impinging
      jet method. The hydrodynamic radius of PEI, determined by PCS measurements, was
      5.3 nm. The electrophoretic mobility of PEI was measured as a function of pH for
      ionic strengths of 10(-3) and 10 (-2) M, which made it possible one to determine
      the amount of electrokinetic charge of the molecule and its zeta potential.
      Formation of the polyelectrolyte layer on mica was followed by measuring the
      streaming potential in the parallel-plate channel. From these measurements, the
      dependence of the apparent zeta potential of mica on the surface coverage of PEI
      was determined. The amount of adsorbed PEI on mica was calculated from the
      convective diffusion theory. These results were quantitatively interpreted in
      terms of the theoretical model postulating a particle-like adsorption mechanism
      for PEI with not too significant shape deformation upon adsorption. On the other
      hand, the Gouy-Chapman model postulating the adsorption in the form of flat disks
      was proved inappropriate. After the surface was fully characterized, particle
      deposition experiments were carried out with the aim of finding the correlation
      between the polymer coverage and the initial rate of latex particle deposition.
      In the range of small polyelectrolyte coverage, a monotonic relation between the
      polymer coverage and the initial deposition rate of particles, as well as the
      jamming coverage, was found. For Theta(PEI)>0.25, the initial particle deposition
      rate attained the value predicted from the convective diffusion theory for
      homogeneous surfaces. These results were interpreted theoretically by postulating
      that an effective immobilization of colloid particles occurred on local
      polyelectrolyte assemblages containing between two and three PEI molecules.

PMID- 17521664
TI  - Influence of aqueous aging on surface properties of plasma sprayed oxide
      coatings.
AB  - The influence of aging in mild aqueous conditions (pH 4, 7 and 9) on surface
      properties of plasma sprayed oxide was studied using electrophoretic mobility
      studies and measuring concentrations of dissolved species from exposure liquids.
      In addition, required acid/base additions to maintain constant pH, redox
      potentials suspension conductivities were measured. The experiment time was two
      weeks. The plasma sprayed materials were based on Al(2)O(3), TiO(2) and
      Cr(2)O(3). Materials based on Al(2)O(3) dissolved easily at pH 4 due to presence
      of metastable gamma-Al(2)O(3) phase. In addition there was clear change in
      surface charging properties (zeta potential) of Al(2)O(3) surfaces so that the
      estimated IEP value drifted from >9 at the beginning of aging and dropped down to
      8.5-8.7 after 2 weeks of treatment. Plasma sprayed TiO(2) did not dissolve under
      the experiment conditions. Even thought the surface charging (zeta potential)
      changed during the exposure, the estimated IEP remained close to the values
      reported for pure TiO(2) materials. Plasma sprayed Cr(2)O(3) based materials were
      also insoluble at the studied pH values. On the other hand, the estimated IEP
      values deviated radically from the reported PZC values of similar materials.

PMID- 17521665
TI  - Avoiding "mud" cracks during drying of thin films from aqueous colloidal
      suspensions.
AB  - The critical cracking thickness of films obtained by drying aqueous alumina
      suspensions has been investigated. The effects of solution chemistry, binder and
      binder crosslinking were studied. Films formed from flocculated and dispersed
      suspensions are compared. The influence of the addition of the polymeric binder,
      poly(vinyl alcohol) (PVA) was also investigated. In addition, in some of the
      dispersed suspensions the PVA was covalently crosslinked. The critical cracking
      thickness is found to be 3 times greater for the films obtained from dispersed
      suspensions than for the films obtained from flocculated suspensions. The
      superior mechanical properties are primarily due to the higher final solids
      concentration in the films obtained from dispersed suspensions. Addition of PVA
      leads to an increase of the critical cracking thickness by a factor of two for
      both dispersed and flocculated systems. When the PVA is crosslinked, the
      mechanical properties of the gel during drying are improved and the critical
      cracking thickness is increased 10 fold with respect to the suspensions with
      uncrosslinked PVA.

PMID- 17521666
TI  - A cell line (NTU-MV) established from Maruca vitrata (Lepidoptera: Pyralidae):
      Characterization, viral susceptibility, and polyhedra production.
AB  - Here we describe the establishment of a new cell line, NTU-MV, derived from pupal
      tissues of an economically important pest, the legume pod borer Maruca vitrata.
      This cell line contained four major cell types: polymorphic cells, round cells,
      spindle-shaped cells, and comma cells. The doubling time of MV cells in TNM-FH
      medium supplemented with 8% FBS at 28 degrees C was 27h. The chromosome numbers
      of MV cells varied widely from 16 to 268. Compared to other insect cell lines,
      the MV cell line produced distinct isozyme patterns with esterase, malate
      dehydrogenase (MDH), and lactate dehydrogenase (LDH). Confirmation that NTU-MV
      was derived from M. vitrata was demonstrated by showing that the sequence of the
      internal transcribed spacer regions (ITS) of the MV cells was 98% identical to
      that of M. vitrata larvae. Two NTU-MV cell strains, NTU-MV1 and NTU-MV56, were
      selected based on susceptibility to MaviMNPV (M. vitrata multiple
      nucleopolyhedrovirus). NTU-MV, MV1, and MV56 cells showed a high susceptibility
      to MaviMNPV and produced high yields of polyhedra (47-50OBs/cell, 4x10(7)
      5.96x10(7)OBs/ml) after 2 weeks of MaviMNPV infection. We conclude that the NTU
      MV cell line will be a useful tool for studying MaviMNPV as well as for the mass
      production of MaviMNPV polyhedra for the biocontrol of M. vitrata.

PMID- 17521667
TI  - Effects of temperature, pH and salinity on the infection of Leptolegnia chapmanii
      Seymour (Peronosporomycetes) in mosquito larvae.
AB  - The effects of temperature, pH, and NaCl concentrations on the infectivity of
      zoospores of Leptolegnia chapmanii (Argentine isolate) were determined for Aedes
      aegypti and Culex pipiens under laboratory conditions. Zoospores of L. chapmanii
      were infectious at temperatures between 10 and 35 degrees C but not at 5 or 40
      degrees C. At the permissive temperatures, mortality rates in young instars were
      much higher than in older instars and larvae of Ae. aegypti were more susceptible
      to L. chapmanii than larvae of Cx. pipiens. At 25 degrees C, Ae. aegypti larvae
      challenged with L. chapmanii zoospores resulted in 100% infection at pH levels
      ranging from 4 to 10. Larvae of Cx. pipiens exposed to similar pH and zoospore
      concentrations resulted in increasing mortality rates from 62% to 99% at pH 4 to
      7, respectively, and then decreased to 71% at pH 10. Aedes aegypti larvae exposed
      to L. chapmanii zoospores in NaCl concentrations ranging from 0 to 7 parts per
      thousand (ppt) at 25 degrees C resulted in 100% mortality while mortality rates
      for Cx. pipiens decreases from 96% in distilled water to 31.5% in water with 6
      ppt NaCl. Control Cx. pipiens larvae died when exposed at a NaCl concentration of
      7 ppt. Vegetative growth of L. chapmanii was negatively affected by NaCl
      concentrations. These results have demonstrated that the Argentinean isolate of
      L. chapmanii tolerated a wide range of temperatures, pH, and salinity, suggesting
      that it has the potential to adapt to a wide variety of mosquito habitats.

PMID- 17521668
TI  - An asymmetric structure of the Bacillus subtilis replication terminator protein
      in complex with DNA.
AB  - In Bacillus subtilis, the termination of DNA replication via polar fork arrest is
      effected by a specific protein:DNA complex formed between the replication
      terminator protein (RTP) and DNA terminator sites. We report the crystal
      structure of a replication terminator protein homologue (RTP.C110S) of B.
      subtilis in complex with the high affinity component of one of its cognate DNA
      termination sites, known as the TerI B-site, refined at 2.5 A resolution. The 21
      bp RTP:DNA complex displays marked structural asymmetry in both the homodimeric
      protein and the DNA. This is in contrast to the previously reported complex
      formed with a symmetrical TerI B-site homologue. The induced asymmetry is
      consistent with the complex's solution properties as determined using NMR
      spectroscopy. Concomitant with this asymmetry is variation in the protein:DNA
      binding pattern for each of the subunits of the RTP homodimer. It is proposed
      that the asymmetric "wing" positions, as well as other asymmetrical features of
      the RTP:DNA complex, are critical for the cooperative binding that underlies the
      mechanism of polar fork arrest at the complete terminator site.

PMID- 17521669
TI  - Cytotoxicity of insulin within its self-assembly and amyloidogenic pathways.
AB  - Solvational perturbations were employed to selectively tune the aggregational
      preferences of insulin at 60 degrees C in vitro in purely aqueous acidic solution
      and in the presence of the model co-solvent ethanol (EtOH) (at 40%(w/w)). Dynamic
      light scattering (DLS), thioflavin T (ThT)-fluorescence, Fourier transform
      infrared (FTIR) and atomic force microscopy (AFM) techniques were employed to
      characterize these pathways biophysically with respect to the pre-aggregational
      assembly of the protein, the aggregation kinetics, and finally the aggregate
      secondary structure and morphology. Using cell viability assays, the results were
      subsequently correlated with the cytotoxicity of the insulin species that form in
      the two distinct aggregation pathways. In the cosolvent-free solution,
      predominantly dimeric insulin self-assembles via the well-known amyloidogenic
      pathway, yielding exclusively fibrillar aggregates, whereas in the solution
      containing EtOH, the aggregation of predominantly monomeric insulin proceeds via
      a pathway that leads to exclusively non-fibrillar, amorphous aggregates.
      Initially present native insulin assemblies as well as partially unfolded
      monomeric species and low molecular mass oligomeric aggregates could be ruled out
      as direct and major cytotoxic species. Apart from the slower overall aggregation
      kinetics under amorphous aggregate promoting conditions, which is due to the
      chaotropic nature of high EtOH concentrations, however, both pathways were
      unexpectedly found to evoke insulin aggregates that were cytotoxic to cultured
      rat insulinoma cells. The observed kinetics of the decrease of cell viabilities
      correlated well with the results of the DLS, ThT, FTIR and AFM studies, revealing
      that the formation of cytotoxic species correlated well with the formation of
      large-sized, beta-sheet-rich assemblies (>500 nm) of both fibrillar and amorphous
      nature. These results suggest that large-sized, beta-sheet-rich insulin
      assemblies of both fibrillar and amorphous nature are toxic to pancreatic beta
      cells. In the light of the ongoing discussion about putative cytotoxic effects of
      prefibrillar and fibrillar amyloid aggregates, our results support the hypothesis
      that, in the case of insulin, factors other than the specific secondary or
      quarternary structural features of the various different aggregates may define
      their cytotoxic properties. Two such factors might be the aggregate size and the
      aggregate propensity to expose hydrophobic surfaces to a polar environment.

PMID- 17521670
TI  - Molecular and structural basis for redox regulation of beta-actin.
AB  - An essential consequence of growth factor-mediated signal transduction is the
      generation of intracellular H(2)O(2). It operates as a second messenger in the
      control of actin microfilament dynamics, causing rapid and dramatic changes in
      the morphology and motile activity of stimulated cells. Little is understood
      about the molecular mechanisms causing these changes in the actin system. Here,
      it is shown that H(2)O(2) acts directly upon several levels of this system, and
      some of the mechanistic effects are detailed. We describe the impact of oxidation
      on the polymerizability of non-muscle beta/gamma-actin and compare with that of
      muscle alpha-actin. Oxidation of beta/gamma-actin can cause a complete loss of
      polymerizability, crucially, reversible by the thioredoxin system. Further,
      oxidation of the actin impedes its interaction with profilin and causes
      depolymerization of filamentous actin. The effects of oxidation are critically
      dependent on the nucleotide state and the concentration of Ca(2+). We have
      determined the crystal structure of oxidized beta-actin to a resolution of 2.6 A.
      The arrangement in the crystal implies an antiparallel homodimer connected by an
      intermolecular disulfide bond involving cysteine 374. Our data indicate that this
      dimer forms under non-polymerizing and oxidizing conditions. We identify
      oxidation of cysteine 272 in the crystallized actin dimer, likely to a cysteine
      sulfinic acid. In beta/gamma-actin, this is the cysteine residue most reactive
      towards H(2)O(2) in solution, and we suggest plausible structural determinants
      for its reactivity. No other oxidative modification was obvious in the structure,
      highlighting the specificity of the oxidation by H(2)O(2). Possible consequences
      of the observed effects in a cellular context and their potential relevance are
      discussed.

PMID- 17521671
TI  - Relationship of immunologic abnormalities and disease stage in multiple
      sclerosis: implications for therapy.
AB  - Multiple sclerosis is classified as an inflammatory cell-mediated autoimmune
      disease directed against central nervous system myelin. Different stages of
      disease appear to be related to different patterns of inflammation and changes on
      MRI. It is postulated that the lack of response to anti-inflammatory drugs in the
      secondary progressive stage relates to a neurodegenerative component that is
      immune independent. However, there is also evidence that the immune system itself
      is more abnormal in the secondary progressive phase according to a number of
      immune measures including dendritic cell function in the peripheral blood.
      Furthermore, neuropathologic studies suggest that there is inflammation in the
      brain of MS patients in the progressive stages in which inflammation takes a
      different form that includes a diffuse inflammatory process in the brain and
      activation of microglial cells. In summary, this implies that there may be
      different types of inflammation depending on the stage of MS with abnormalities
      in adaptive immunity playing an important role in the relapsing-remitting stage
      and innate immunity a more important role in the progressive stage.

PMID- 17521672
TI  - "Thinking without thinking" about natalizumab and PML.
AB  - The novel multiple sclerosis (MS) therapeutic natalizumab has taken neurologists
      and their MS patients on a roller-coaster ride: initial encouraging efficacy data
      led to expedited release in the United States, followed by suspension of dosing
      with the unexpected occurrence of progressive multifocal leukoencephalopathy
      (PML) in three clinical trial participants. The drug was re-released in 2006, in
      a restricted distribution format. Aside from PML, natalizumab treatment was not
      associated with opportunistic infections, suggesting the possibility that PML in
      these individuals was mechanism-based, and was not a consequence of generalized
      immunosuppression. This commentary proposes a hypothesis to account for PML in
      natalizumab-treated patients.

PMID- 17521673
TI  - Cortical sulcal effacement on brain CT associated with cerebral hyperperfusion
      after carotid artery stenting.
AB  - We present two patients with reversible neurologic deficits after carotid artery
      stenting. The patients showed diffuse cortical sulcal effacement without
      parenchymal hypoattenuation on brain non-contrast CT as well as mild
      hyperperfusion on perfusion imaging. There was no white matter edema or
      intracerebral hemorrhage in either patient. We speculated that hyperperfusion
      after carotid artery stenting could be the underlying cause of the cortical
      sulcal effacement on brain CT in the absence of prominent cytotoxic or vasogenic
      edema.

PMID- 17521674
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy presenting as cauda
      equina syndrome in a diabetic.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) may occur in
      association with diabetes mellitus (DM). We report a case of a poorly controlled
      diabetic patient who presented with rapid onset of bilateral lower extremity
      weakness and sensory loss associated with sacral and posterior thigh paresthesias
      and urinary and bowel incontinence, indicative of cauda equina syndrome (CES).
      Subsequent evaluation was consistent with CIDP. Monthly infusions with
      intravenous immunoglobulins (IVIg) with strict glycemic control using insulin
      resulted in remarkable clinical and electrophysiological recovery. This case
      report describes a rare presentation of CIDP and emphasizes the importance of
      early utility of electrodiagnostic (EDX) studies in the clinical evaluation of
      diabetic patients presenting with rapidly progressive lower extremity weakness
      and sensory loss associated with diminished reflexes.

PMID- 17521675
TI  - Modeling fish population movements: from an individual-based representation to an
      advection-diffusion equation.
AB  - In this paper, we address the problem of modeling fish population movements. We
      first consider a description of movements at the level of individuals. An
      individual-based model is formulated as a biased random walk model in which the
      velocity of each fish has both a deterministic and a stochastic component. These
      components are function of a habitat suitability index, h, and its spatial
      gradient nablah. We derive an advection-diffusion partial differential equation
      (PDE) which approximates this individual-based model (IBM). The approximation
      process enables us to obtain a mechanistic representation of the advection and
      diffusion coefficients which improves the heuristic approaches of former studies.
      Advection and diffusion are linked and exhibit antagonistic behaviors: strong
      advection goes with weak diffusion leading to a directed movement of fish. On the
      contrary weak advection goes with strong diffusion corresponding to a searching
      behavior. Simulations are conducted for both models which are compared by
      computing spatial statistics. It is shown that the PDE model is a good
      approximation to the IBM.

PMID- 17521678
TI  - Prognostic impact of tumor size on pT2 renal cell carcinoma: an international
      multicenter experience.
AB  - PURPOSE: The current tumor classification for renal cell carcinoma classifies pT2
      tumors as larger than 7 cm in greatest dimension and limited to the kidney. We
      examined the current pT2 tumor classification of renal cell carcinoma and
      determined whether a tumor size cutoff exists that would improve prognostic
      accuracy. MATERIALS AND METHODS: We studied 706 patients with pT2 renal cell
      carcinoma treated with surgical extirpation at 9 international academic centers.
      Data collected from each patient included age at diagnosis, gender, 2002 TNM
      (tumor, node, metastasis) stage, tumor size, nuclear grade, performance status,
      histological subtype and disease specific survival. Disease specific survival was
      evaluated with univariate and multivariate analysis. RESULTS: Median followup was
      52 months. Univariate Cox regression analysis showed a significant association of
      tumor size with disease specific survival (HR 1.11, p<0.001). An ideal tumor size
      cutoff of 11 cm was identified, which led to the stratification of 2 groups with
      respect to disease specific survival (p<0.0001) with 5 and 10-year survival rates
      of 73% and 65% for pT2 11 cm or less, and 57% and 49% for pT2 larger than 11 cm,
      respectively. The incidence of metastases was significantly greater in the larger
      than 11 cm group, while Eastern Cooperative Oncology Group performance status,
      Fuhrman grade and histological subtype were similar. Multivariate Cox regression
      analysis retained tumor size as an independent prognostic factor and as the
      strongest prognostic factor for patients with pT2N0M0 disease. CONCLUSIONS: Our
      data suggest that the current pT2 classification can be improved by
      subclassification into pT2a and pT2b based on a tumor size cutoff of 11 cm.
      Patients in the proposed pT2bN0M0 group are at higher risk for death from renal
      cell carcinoma and should be considered for adjuvant therapies. External
      validation is warranted before suggesting change to the TNM classification.

PMID- 17521679
TI  - Tissue specific increase of the catalytic subunits of the 26S proteasome by
      indirect antioxidant dithiolethione in mice: enhanced activity for degradation of
      abnormal protein.
AB  - Decreases in the 26S proteasome are related to the toxicities of abnormal protein
      aggregates and may contribute to pathogenesis of degenerative diseases.
      Therefore, maintenance of proteasome function can be a novel strategy to protect
      cells against abnormal protein-mediated toxicity. In the present study, we have
      demonstrated the tissue specific increase of the catalytic subunits of the
      proteasome in mice following oral administration of 3H-1,2-dithiole-3-thione
      (D3T, 0.5 mmol/kg), which functions as a cancer preventive agent in animal and
      human studies. Expression of the 20S catalytic core subunits PSMB5, PSMB6, and
      PSMB7 were increased in liver, lung, small intestine, and colon of mice at 24 h
      after D3T treatment. Elevated expression of proteasome catalytic subunits led to
      increases in proteasomal peptidase activities in these tissues. Oral
      administration of D3T also exerted a pharmacodynamic action in some brain regions
      of these mice and proteasomal peptidase activities were significantly elevated in
      the cerebral cortex-hippocampus. Moreover, tissue extracts from D3T-treated mice
      and cell lysates obtained from D3T-incubated murine neuroblastoma cells exhibited
      the enhanced capacity to degrade mutant human SOD1G93A protein. These results
      indicate that the catalytic subunits of the 26S proteasome are inducible in
      multiple tissues of mouse including brain by exogenous chemical treatment.
      Increased proteasome expression by inducers may have a role in
      protection/attenuation of protein aggregate-mediated disorders.

PMID- 17521680
TI  - Topiramate reduced sweat secretion and aquaporin-5 expression in sweat glands of
      mice.
AB  - Decreased sweat secretion is a primary side effect of topiramate in pediatric
      patients, but the mechanism underlying this effect remains unclear. This study
      aimed to better understand how topiramate decreases sweat secretion by examining
      its effect on the expression of carbonic anhydrase (CA) II and aquaporin-5
      (AQP5), total CA activity, as well as on tissue morphology of sweat glands in
      mice. Both developing and mature mice were treated with a low (20 mg/kg/day) and
      high dose (80 mg/kg/day) of topiramate for 4 weeks. Sweat secretion was
      investigated by an established technique of examining mold impressions of hind
      paws. CA II and AQP5 expression levels were determined by immunofluorescence and
      immunoblotting and CA activity by a colorimetric assay. In mature mice,
      topiramate treatment decreased the number of pilocarpine reactive sweat glands
      from baseline in both the low and high dose groups by 83% and 75%, respectively.
      A similar decrease was seen in developing mice. Mature mice with reactive sweat
      glands that declined more than 25% compared to baseline were defined as
      anhidrotic mice. These mice did not differ from controls in average secretory
      coil diameter, CA II expression and CA activity. In contrast, anhidrotic mice did
      show a reduction in membrane AQP5 expression in sweat glands after topiramate
      delivery. Thus, sweat secretion and membrane AQP5 expression in mouse sweat
      glands decreased following topiramate administration. These results suggest
      dysregulation of AQP5 may be involved in topiramate-induced hypohidrosis and
      topiramate may serve as a novel therapy for hyperhidrosis.

PMID- 17521681
TI  - Heteroclinic orbits indicate overexploitation in predator-prey systems with a
      strong Allee effect.
AB  - Species establishment in a model system in a homogeneous environment can be
      dependent not only on the parameter setting, but also on the initial conditions
      of the system. For instance, predator invasion into an established prey
      population can fail and lead to system collapse, an event referred to as
      overexploitation. This phenomenon occurs in models with bistability properties,
      such as strong Allee effects. The Allee effect then prevents easy re
      establishment of the prey species. In this paper, we deal with the bifurcation
      analyses of two previously published predator-prey models with strong Allee
      effects. We expand the analyses to include not only local, but also global
      bifurcations. We show the existence of a point-to-point heteroclinic cycle in
      these models, and discuss numerical techniques for continuation in parameter
      space. The continuation of such a cycle in two-parameter space forms the boundary
      of a region in parameter space where the system collapses after predator
      invasion, i.e. where overexploitation occurs. We argue that the detection and
      continuation of global bifurcations in these models are of vital importance for
      the understanding of the model dynamics.

PMID- 17521682
TI  - Etheno-DNA adduct formation in rats gavaged with linoleic acid, oleic acid and
      coconut oil is organ- and gender specific.
AB  - Intake of linoleic acid (LA) increased etheno-DNA adducts induced by lipid
      peroxidation (LPO) in white blood cells (WBC) of female but not of male
      volunteers [J. Nair, C.E. Vaca, I. Velic, M. Mutanen, L.M. Valsta, H. Bartsch,
      High dietary omega-6 polyunsaturated fatty acids drastically increase the
      formation of etheno-DNA adducts in white blood cells of female subjects, Cancer
      Epidemiol. Biomarkers Prev. 6 (1997) 597-601]. Etheno-adducts were measured in
      rats gavaged with LA, oleic acid (OA) and saturated fatty acid rich coconut oil
      for 30 days. DNA from organs and total WBC was analyzed for 1, N(6)
      ethenodeoxyadenosine (varepsilondA) and 3, N(4)-ethenodeoxycytidine
      (varepsilondC) by immunoaffinity/(32)P-postlabeling. Colon was the most affected
      target with LA-treatment, where etheno-adducts were significantly elevated in
      both sexes. In WBC both adducts were elevated only in LA-treated females.
      Unexpectedly, OA treatment enhanced etheno-adduct levels in prostate 3-9 fold.
      Our results in rodents confirm the gender-specific increase of etheno-adducts in
      WBC-DNA, likely due to LPO induced by redox-cycling of 4-hydroxyestradiol. Colon
      was a target for LPO-derived DNA-adducts in both LA-treated male and female rats,
      supporting their role in omega-6 PUFA induced colon carcinogenesis.

PMID- 17521683
TI  - Chronic psychological stress enhances nociceptive processing in the urinary
      bladder in high-anxiety rats.
AB  - This study sought to determine whether acute and/or chronic psychological stress
      produce changes in urinary bladder nociception. Female Sprague-Dawley (SD;
      low/moderate anxiety) or Wistar-Kyoto (WK; high-anxiety) rats were exposed to
      either an acute (1 day) or a chronic (10 days) water avoidance stress paradigm or
      a sham stress paradigm. Paw withdrawal thresholds to mechanical and thermal
      stimuli and fecal pellet output, were quantified at baseline and after the final
      stress or sham stress exposure. Rats were then sedated, and visceromotor
      responses (VMRs) to urinary bladder distension (UBD) were recorded. While acute
      stress exposure did not significantly alter bladder nociceptive responses in
      either strain of rats, WK rats exposed to a chronic stress paradigm exhibited
      enhanced responses to UBD. These high-anxiety rats also exhibited somatic
      analgesia following acute, but not chronic, stress. Furthermore, WK rats had
      greater fecal pellet output than SD rats when stressed. Significant stress
      induced changes in nociceptive responses to mechanical stimuli were observed in
      SD rats. That chronic psychological stress significantly enhanced bladder
      nociceptive responses only in high-anxiety rats provides further support for a
      critical role of genetics, stress and anxiety as exacerbating factors in painful
      urogenital disorders such as interstitial cystitis (IC).

PMID- 17521684
TI  - Brain-adipose tissue neural crosstalk.
AB  - The preponderance of basic obesity research focuses on its development as
      affected by diet and other environmental factors, genetics and their
      interactions. By contrast, we have been studying the reversal of a naturally
      occurring seasonal obesity in Siberian hamsters. In the course of this work, we
      determined that the sympathetic innervation of white adipose tissue (WAT) is the
      principal initiator of lipid mobilization not only in these animals, but in all
      mammals including humans. We present irrefutable evidence for the sympathetic
      nervous system (SNS) innervation of WAT with respect to neuroanatomy (including
      its central origins as revealed by transneuronal viral tract tracers),
      neurochemistry (norepinephrine turnover studies) and function (surgical and
      chemical denervation). A relatively unappreciated role of WAT SNS innervation
      also is reviewed--the control of fat cell proliferation as shown by selective
      chemical denervation that triggers adipocyte proliferation, although the precise
      mechanism by which this occurs presently is unknown. There is no, however,
      equally strong evidence for the parasympathetic innervation of this tissue;
      indeed, the data largely are negative severely questioning its existence and
      importance. Convincing evidence also is given for the sensory innervation of WAT
      (as shown by tract tracing and by markers for sensory nerves in WAT), with
      suggestive data supporting a possible role in conveying information on the degree
      of adiposity to the brain. Collectively, these data offer an additional or
      alternative view to the predominate one of the control of body fat stores via
      circulating factors that serve as efferent and afferent communicators.

PMID- 17521685
TI  - Afternoon T: testosterone level is higher in red than yellow male polychromatic
      lizards.
AB  - Recent work on within-species polymorphism across a broad range of taxa has
      renewed and considerably increased the attention to this classic evolutionary
      area, notably in lizard species where colors covary with reproductive strategies.
      We demonstrate elsewhere that red-headed males beat yellow-headed males in staged
      contests for females in the Australian painted dragon lizard Ctenophorus pictus.
      This morph difference in behaviour is linked to what appears to be a convention
      of red dominance in male-male interactions set very early in ontogeny, long
      before coloration has developed. In the current note, we investigate the
      relationship between time of day, which is directly linked to vigilance time in
      territorial males, and plasma levels of testosterone and corticosterone. We show
      that red males have higher testosterone levels in late afternoon following a day
      of territory patrolling and a non-significant trend in plasma corticosterone
      levels that decline with time of day. In conclusion, there are significant
      differences in testosterone profile between the two color morphs, providing a
      potential proximate link to the behavioural differences between them.

PMID- 17521686
TI  - Cannabinoid CB1 receptor inverse agonists and neutral antagonists: effects on
      food intake, food-reinforced behavior and food aversions.
AB  - Drugs that interfere with cannabinoid CB1 receptor transmission suppress a number
      of food-related behaviors, and these compounds are currently being assessed for
      their potential utility as appetite suppressants. In addition to rimonabant
      (SR141716A), several other compounds have been evaluated, including AM251 and
      AM1387. Biochemical studies indicate that most of the drugs assessed thus far
      have been CB1 inverse agonists, and these drugs all act to suppress food intake
      and disrupt food-reinforced behavior. Behavioral tests involving intake of
      different diets (i.e., high fat, high carbohydrate, laboratory chow) indicate
      that consumption of all three food types is disrupted by CB1 inverse agonists,
      and that, expressed as a percent of baseline intake, the effect is roughly
      comparable across different diets. Although CB1 inverse agonists do not appear to
      produce severe motor impairments that disrupt feeding behavior, there is evidence
      that they can induce nausea and malaise. Recent studies have been undertaken to
      characterize the behavioral effects of CB1 receptor neutral antagonists such as
      AM4113 to determine if these drugs can reduce feeding and food-reinforced
      behaviors. Across a variety of different tests, AM4113 produces effects on food
      motivated behavior that are very similar to those produced by CB1 inverse
      agonists. Moreover, this drug did not induce conditioned gaping in rats or
      vomiting in ferrets. These results suggest that CB1 receptor neutral antagonists
      may decrease appetite by blocking endogenous cannabinoid tone, and that these
      drugs may be less associated with nausea than is the case for CB1 inverse
      agonists.

PMID- 17521687
TI  - Enhanced short-latency responses in the ventral posterior medial (VPM) thalamic
      nucleus following whisker trimming in the adult rat.
AB  - This study examined the effects of whisker trimming on the functional
      organization of the adult somatosensory thalamus. In vivo extracellular unit
      recordings were made on ventral posterior medial (VPM) thalamic neurons in
      urethane anaesthetised adult rats. Neuronal response properties to controlled
      whisker deflection were recorded in untrimmed control animals and in animals
      where one row of whiskers had been trimmed for a median of 18 days. Trimming
      significantly increased short-latency responses to stimulation of the centre
      receptive field whisker (mean increase of 36%, p<.001). Longer latency responses
      to surround receptive field whiskers were unaffected. Spontaneous firing was
      significantly decreased in trimmed animals. A condition-test paradigm indicated
      that thalamic inhibition was reduced following whisker trimming, although this
      effect failed to reach statistical significance. These results demonstrate a
      capacity of the adult somatosensory thalamus to undergo functional reorganization
      in response to non-traumatic and innocuous whisker trimming.

PMID- 17521688
TI  - Distribution of mast cell subtypes and immune cell populations in canine
      intestines: evidence for age-related decline in T cells and macrophages and
      increase of IgA-positive plasma cells.
AB  - The distribution and numbers of leucocytes and mast cells (MC) in the canine
      gastrointestinal tract of three different age groups was investigated
      immunhistochemically. In all age groups, CD3+ T cells were more prominent in the
      villus region than in the crypt areas without differences between intestinal
      segments, whereas macrophages were more randomly distributed. Kresylecht-violet
      and tryptase-positive MC were prominent in pericrypt regions with statistic
      significances. Chymase-bearing mast cells, IgA-, IgG- and IgM-containing cells
      did not show significant differences in their distribution but, except for IgG
      positive cells, subjective trends with increasing numbers towards the crypts
      exist. The reasons for the distribution of T cells, macrophages, immunoglobulin
      containing cells and mast cells are not clear. Lamina propria CD3+ T cells and
      macrophages significantly decreased whilst a significant increase of IgA
      containing plasma cells with increasing age was found. For mast cell subtypes,
      IgG- and IgM-containing cells no significant changes in numbers with increasing
      age exist.

PMID- 17521689
TI  - Characterisation of Mannheimia spp. strains isolated from bovine nasal exudate
      and factors associated to isolates, in dairy farms in the Central Valley of
      Mexico.
AB  - Mannheimia spp. strains obtained from bovine nasal exudates of either clinically
      healthy or clinically affected by respiratory tract disease animals were isolated
      and characterised to estimate the prevalence of isolated serotypes in dairy farms
      in Mexico, by means of a trans-sectional descriptive study. Strains were isolated
      and typified through biochemical and immunological tests. chi(2) or Fisher
      statistical tests were applied, as well as odds ratio calculation and logistic
      regression analysis to evaluate the association and effect of some variables on
      Mannheimia spp. isolation. The apparent prevalence rates of Mannheimia
      haemolytica was significantly higher in diseased bovines (OR = 1.94; p < 0.05),
      as well as in bovines younger than 1 year of age (OR = 23.98; p < 0.05), and in
      bovines not vaccinated against bovine pasteurellosis (OR = 1.52; p < 0.05). Age
      was the variable that remained in the logistic regression model. Serotype A1
      showed the highest prevalence, even when most isolates were not-typable. Bovines
      younger than one year of age and those with disease were the groups with the
      highest frequency of M. haemolytica and Mannheimia glucosida isolates.

PMID- 17521690
TI  - The effect of dietary supplementation with 9-cis:12-trans and 10-trans:12-cis
      conjugated linoleic acid (CLA) for nine months on serum cholesterol, lymphocyte
      proliferation and polymorphonuclear cells function in Beagle dogs.
AB  - Conjugated linoleic acids (CLA), 9-cis:11-trans and 10-trans:12-cis, have been
      shown to be able to modify some immune cells parameters and plasma lipids in a
      variety of experiment models. Since lymphocytes and polymorphonuclear cells
      (PMNC) have a large spectrum functions in the immune response, the knowledge in
      this field has to be expanded. Beagle dogs were fed a control diet or a CLA
      supplemented diet for nine months. Blood was collected for biochemical analysis
      and lymphocyte and PMNC isolation. PMNC were assayed for lysosome content,
      phagocytic activity and superoxide anion production. A lymphocyte proliferation
      capacity assay was done. The CLA fed dogs had a 34% reduction in total
      cholesterol (P < 0.05), 28% in LDL (P < 0.05) and 28% non-HDL-cholesterol (P <
      0.05). Neither of the PMNC parameters evaluated demonstrated significant
      alteration. Lymphocytes from CLA group increased by 45% their mitotic capacity (P
      < 0.05). Our study demonstrates that CLA can successfully modify the lipid
      profile of dogs (monogastrics) when fed at reasonable levels, but did not
      significantly alter inflammatory function as would generally predicted. Further,
      we had some indication that CLA modulated T cell responsiveness.

PMID- 17521691
TI  - Role of mitochondrial permeability transition in human renal tubular epithelial
      cell death induced by aristolochic acid.
AB  - Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a
      progressive tubulointerstitial nephropathy. However, the mechanism by which AA
      causes renal injury remains largely unknown. Here we reported that the
      mitochondrial permeability transition (MPT) plays an important role in the renal
      injury induced by aristolochic acid I (AAI). We found that in the presence of
      Ca(2+), AAI caused mitochondrial swelling, leakage of Ca(2+), membrane
      depolarization, and release of cytochrome c in isolated kidney mitochondria.
      These alterations were suppressed by cyclosporin A (CsA), an agent known to
      inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for
      24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane
      depolarization, cytochrome c release, and increase of caspase 3 activity. These
      toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another
      specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of
      mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We
      suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken
      together, these results suggested that MPT plays a critical role in the
      pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might
      contribute to human nephrotoxicity of aristolochic acid.

PMID- 17521692
TI  - Effects of microcystin-LR on mouse lungs.
AB  - Toxic cyanobacteria blooms in drinking water supplies have been an increasing
      public health concern all over the world. Human populations can be exposed to
      microcystins, an important family of cyanotoxins, mainly by oral ingestion.
      However, inhalation from recreational water and hemodialysis can represent other
      routes. This study investigated changes in respiratory mechanics, histology,
      protein phosphatase (PP) 1 and 2A activity and microcystin in lung of adult mice
      injected intraperitoneally (i.p.) with microcystin-LR. Thirty-six mice were
      divided into control (CTRL) and test (CYANO) groups. CTRL group received an i.p.
      injection of saline and the CYANO group received 40 microg MCYST-LR/kg i.p. After
      2 and 8 h, and 1, 2 and 4 days after toxin injection, six mice from each group
      were sampled for analyses. Resistive and viscoelastic pressures, static and
      dynamic elastances augmented at 2 h in CYANO and so remained until day 4.
      Alveolar collapse and inflammatory cell infiltration were found 2h after the
      injection, reaching peak values at 8 h. However, no microcystin or inhibition of
      PPases could be detected in mice lungs. In conclusion, MCYST-LR led to a rapid
      increase in lung impedance and an inflammatory response with interstitial edema
      and inflammatory cell recruitment in mice.

PMID- 17521693
TI  - JE Nakayama/JE SA14-14-2 virus structural region intertypic viruses: biological
      properties in the mouse model of neuroinvasive disease.
AB  - A molecular clone of Japanese encephalitis (JE) virus Nakayama strain was used to
      create intertypic viruses containing either the 5'-C-prM-E or the prM-E region of
      the attenuated JE SA14-14-2 virus in the JE Nakayama background. These two
      intertypic JE viruses, JE-X/5'CprME(S) and JE-X/prME(S), respectively, generally
      resembled the parental JE virus in cell culture properties. Similar to virus
      derived from the JE Nakayama molecular clone (JE-XJN), JE-X/prME(S) was highly
      neuroinvasive and neurovirulent for young adult mice, whereas JE-X/5'CprME(S) was
      attenuated for neuroinvasiveness and only partially attenuated for
      neurovirulence. Immunization of young mice with JE-X/5'CprME(S) virus elicited
      neutralizing antibodies against JE Nakayama virus and conferred protection
      against encephalitis following challenge with JE Nakayama virus. The sequence of
      the JE-X/5'CprME(S) virus differed from that of JE-X/prME(S) virus at two
      nucleotides in the 5' UTR, 3 amino acid positions in the capsid protein, 4
      positions in the prM protein and 1 in the envelope protein. For JE-X/prME(S)
      virus, the 4 differences in prM and the single substitution in the envelope
      represented reversions to the sequence of JE Nakayama virus. Overall, this study
      reveals that molecular determinants associated with the prM-E region of the
      attenuated JE SA14-14-2 virus are insufficient by themselves to confer an
      attenuation phenotype upon JE Nakayama virus. This suggests a role for
      determinants in the 5' UTR and/or the capsid protein of the JE SA 14-14-2 virus
      genome in influencing the virulence properties of the JE Nakayama virus in the
      mouse model.

PMID- 17521694
TI  - Mathematical interpretation of pollutant wash-off from urban road surfaces using
      simulated rainfall.
AB  - In the context of stormwater quality modelling, an in-depth understanding of
      underlying physical processes and the availability of reliable and accurate
      mathematical equations, which can replicate pollutant processes are essential.
      Stormwater pollutants undergo three primary processes, namely, build-up, wash-off
      and transport, before accumulating into receiving waters. These processes are
      expressed mathematically by equations in stormwater quality models. Among the
      three processes, wash-off is the least investigated. This paper presents the
      outcomes of an in-depth investigation of pollutant wash-off processes on typical
      urban road surfaces. The study results showed that a storm event has the capacity
      to wash-off only a fraction of pollutants available and this fraction varies
      primarily with rainfall intensity, kinetic energy of rainfall and characteristics
      of the pollutants. These outcomes suggest that the exponential equation commonly
      used for mathematically defining pollutant wash-off would need to be modified in
      order to incorporate the wash-off capacity of rainfall. Consequently, the
      introduction of an additional term referred to as the 'capacity factor'C(F) is
      recommended. C(F) primarily varies with rainfall intensity. However, for
      simplicity three rainfall intensity ranges were identified where the variation of
      C(F) can be defined. For rainfall intensities less than 40 mm/h, C(F) varies
      linearly from 0 to 0.5. For rainfall intensities from 40 to around 90 mm/h, C(F)
      is a constant around 0.5. Beyond 90 mm/h, C(F) varies between 0.5 and 1.

PMID- 17521695
TI  - Study on the oligosaccharides composition of the water-soluble fraction of marine
      mucilage by electrospray tandem mass spectrometry.
AB  - The massive accumulation of organic matter, which periodically occurs in the
      northern Adriatic Sea, and in other locations worldwide, is presently thought to
      be the results of the aggregation of dissolved organic matter (DOM) into
      particulate organic matter (POM). This phenomenon is the result of human
      activities and propitious weather conditions. Although many aspects of the
      phenomenon are well understood, the trigger mechanisms leading to mucilage
      formation have not been clarified yet, probably as a consequence of inadequate
      analytical approaches. In this context, the recent advancements in LC-MS
      interfacing might contribute in clarifying the mechanism of mucilage formation.
      In the present paper, hydrophilic interaction liquid chromatography coupled with
      electrospray tandem mass spectrometry (HILC-ESI-MS/MS) is proposed as an
      innovative method for the investigation of underivatized oligosaccharides in
      mucilage samples. Recent findings suggest that the significant presence of these
      compounds in seawater can play an important role in the initial steps of the
      agglomeration processes forming gelatinous material. Our results reveal the
      presence of several maltodextrines in the water-soluble fraction of mucilage
      macroaggregates, collected in various locations of the northern Adriatic Sea. In
      our knowledge, the proposed method is the first application of LC-MS in the
      investigation of marine mucilage.

PMID- 17521696
TI  - Study of trace metal leaching from coals into seawater.
AB  - The behaviour of three South African coals in water and, particularly in
      seawater, was examined. A sequential speciation procedure used to evaluate trace
      metal partitioning in coal has shown that trace metals will not be easily
      released from these coals into environmental ecosystems. Only a few trace
      elements are slightly leached from these coals into water or seawater at pH
      around 8. On the other hand, Mn is highly leached from these coals into water or
      seawater. It has been clearly shown that Mn concentrations are highly correlated
      to sulfate and calcium concentrations indicating that Mn is mainly solubilized
      into water simultaneously to gypsum; the leaching efficiency being severely
      reduced for coal having a high calcite content. The leaching percentage of Mn
      into seawater is enhanced by the presence of seawater salts that increases gypsum
      solubility. The leaching process of Mn from coal into water or seawater is
      governed by gypsum solubilization and is relatively rapid during the first thirty
      minutes, then very slow. In this study, it has been also shown that, depending on
      their physico-chemical properties, trace metals may be removed from seawater
      solutions in the presence of coal having a high calcite content. In this work, it
      has been also shown that some elements, particularly Fe, are greatly solubilized
      into seawater in the presence of a strong chelating agent like EDTA. Like for Mn,
      the leaching rate of metals from coal in the presence of EDTA is relatively rapid
      during the first 30 min then much slower, suggesting a solubilization process
      simultaneously to gypsum or/and calcite solubilization.

PMID- 17521697
TI  - Redox reactions in the Fe-As-O2 system.
AB  - We have examined two redox reactions involving arsenic and iron at near-neutral
      pH: the reduction of As(V) by Fe(II) under anoxic conditions, and the co
      oxidation of As(III) during Fe(II) oxygenation. We also considered the impact of
      goethite, pH buffers, and radical scavengers on these reactions. In a series of
      anoxic experiments, Fe(II) was found to reduce As(V) in the presence of goethite,
      but not in homogeneous solution. The reaction rate increased with increasing pH
      and Fe(II) concentration, but in all cases was relatively slow. In aerobic
      experiments, the kinetics of Fe(II) oxygenation at neutral pH, and the
      corresponding oxidation of As(III) were found to depend heavily on pH buffer type
      and concentration. The classic formulation of Fe(II) oxidation by oxygen,
      involving four single-electron transfers, was reviewed and found to be inadequate
      for explaining observed oxidation of Fe(II) and As(III). Widely cited rate
      constants for Fe(II) oxygenation originate from experiments conducted in
      carbonate buffer, and do not match observations made in phosphate, MES, or HEPES
      systems. In phosphate buffer, Fe(II) oxidation is rapid and dependent on
      phosphate concentration. In MES and HEPES buffers, Fe(II) oxidation is much
      slower due to the lack of labile ferrous iron species. Oxygenation of Fe(II)
      appears to proceed through different mechanisms in phosphate and MES or HEPES
      systems. In both cases, reactive intermediary species are produced which can
      oxidize As(III). These oxidants are not the hydroxyl radical, but may be Fe(IV)
      species.

PMID- 17521698
TI  - Extrapulmonary small cell carcinomas express K homology domain containing protein
      overexpressed in cancer, but carcinoid tumors do not.
AB  - A number of malignancies, including high-grade neuroendocrine carcinomas of the
      lung, have been reported to express K homology domain containing protein
      overexpressed in cancer (KOC), a member of the insulin-like growth factor
      messenger RNA-binding protein (IMP) family also known as L523S and IMP3. KOC acts
      to promote tumor cell proliferation by enhancing insulin-like growth factor-II
      protein expression. This study aimed to examine KOC expression pattern in
      extrapulmonary neuroendocrine tumors. Seventy-five extrapulmonary neuroendocrine
      tumors that were surgically resected or had undergone biopsy, including 53 small
      cell carcinomas (uterine cervix, 21; bladder, 10; colorectum, 13; prostate, 7;
      stomach, 1; and esophagus, 1) and 22 carcinoid tumors (colorectum, 10; appendix,
      5; ileum, 4; duodenum, 2; and stomach, 1), were immunohistochemically studied
      using a monoclonal antibody against KOC. Our results demonstrated that 47 small
      cell carcinomas (89%) showed moderate to strong positive staining for KOC, with
      25 cases (53%) showing positivity in more than 90% of tumor cells and 22 cases
      (47%) in 40% to 80% of tumor cells. Three cases showed weak staining in 5% to 10%
      of the tumor cells. The remaining 3 cases (uterine cervix, 2; bladder, 1) showed
      completely negative immunoreactivity. No KOC immunostaining was detected in 22
      carcinoid tumors. These findings indicate that KOC may play an important role in
      the regulation of biologic behavior of extrapulmonary small cell carcinomas. In
      addition, immunohistochemical detection of KOC expression may serve as a useful
      diagnostic tool in the distinction between small cell carcinoma and carcinoid
      tumor, particularly when the diagnostic material is a small biopsy with crushing
      artifact.

PMID- 17521699
TI  - The evolution of collagen expression in sarcomatoid renal cell carcinoma.
AB  - The development of a sarcomatoid morphotype is recognized as an extreme form of
      dedifferentiation in renal cell carcinoma and is associated with a poor
      prognosis. Although sarcomatoid renal cell carcinoma shows pronounced spindle
      cell morphology, clear cell renal cell carcinoma may show early spindle cell
      change with cellular elongation, and the prognostic significance of this is
      debated. To determine the relationship between sarcomatoid renal cell carcinoma
      and clear cell renal cell carcinoma showing early spindle cell change, we have
      investigated collagen expression using immunohistochemistry in these 2 tumor
      types. Both sarcomatoid renal cell carcinoma and early spindle cell change tumors
      showed pericellular interstitial expression of collagen types I and III, whereas
      sarcomatoid renal cell carcinoma also showed cytoplasmic expression of these
      collagen types. Expression of these collagen types in typical clear cell renal
      cell carcinoma was, in occasional cases, limited to faint and patchy staining in
      a pericellular interstitial distribution. Tumor cells did not stain for collagen
      type IV in sarcomatoid renal cell carcinoma, early spindle cell change, or
      typical clear cell renal cell carcinoma. In sarcomatoid renal cell carcinoma,
      there was diffuse pericellular expression of collagen type V and patchy
      pericellular expression of collagen type VI, whereas early spindle cell change
      tumors showed patchy pericellular staining with antibodies to collagen type V.
      Collagen type VI expression in early spindle cell change was largely confined to
      the vascular adventitia and areas of scarring, although very occasional foci of
      faint interstitial staining were also seen. In typical clear cell renal cell
      carcinoma, staining of collagen types V and VI was limited to the vascular
      adventitia and foci of desmoplasia, whereas no staining of tumor cell cytoplasm
      were seen. This study has shown that collagen expression of sarcomatoid renal
      cell carcinoma differs from that of early spindle cell change and provides
      validating evidence that these 2 morphotypes should not be considered together
      for classification purposes.

PMID- 17521700
TI  - Specific pattern of LKB1 and phospho-acetyl-CoA carboxylase protein
      immunostaining in human normal tissues and lung carcinomas.
AB  - The LKB1 tumor suppressor gene codes for a serine/threonine protein kinase, and
      among its substrates is the adenosine monophosphate-dependent protein kinase, a
      sensor of intracellular energy levels. LKB1 is genetically inactivated in several
      types of tumors, especially lung adenocarcinomas. Here we used
      immunohistochemistry to evaluate the levels of LKB1 and the phosphorylated form
      of the acetyl-CoA carboxylase (ACC) protein in a variety of human adult normal
      tissues and in 159 lung carcinomas. The enzyme ACC becomes inactive upon
      phosphorylation by adenosine monophosphate-dependent protein kinase. Our analysis
      in normal tissues revealed strong LKB1 immunostaining in most epithelia, in the
      seminiferous tubules of the testis, in myocytes from skeletal muscle, and in glia
      cells. In contrast to the cytosolic location of LKB1 found in most tissues, glia
      cells carried mainly nuclear LKB1. Some epithelial cells showed apical
      accumulation of LKB1, supporting its role in cell polarity. Regarding phospho-ACC
      (p-ACC), strong immunostaining was observed in myocytes from the skeletal muscle
      and heart, and in Leydig cells of the testis. In lung tumors, LKB1 immunostaining
      was absent, moderate, and high in 20%, 61%, and 19% of the tumors, respectively,
      whereas p-ACC immunostaining was found to be absent/low, moderate, and high in
      35%, 34%, and 31% of the tumors, respectively. High levels of LKB1 and p-ACC
      immunostaining predominated in lung adenocarcinomas compared with squamous cell
      carcinomas. Finally, high p-ACC was an independent marker for prediction of
      better survival in lung adenocarcinoma patients. Median overall survival was
      longer in patients with p-ACC-positive than those with p-ACC-negative tumors (96
      versus 44 months, P = .04). In conclusion, our observations provide complete
      information about the pattern and levels of LKB1 and p-ACC immunostaining in
      normal tissues and in lung tumors, and highlight the special relevance of
      abnormalities of the LKB1 pathway in lung adenocarcinoma.

PMID- 17521701
TI  - Expression characteristics of prostate-derived Ets factor support a role in
      breast and prostate cancer progression.
AB  - The purpose of this study was to understand the characteristics of prostate
      derived Ets factor (PDEF) protein expression in breast and prostate cancer
      progression. A polyclonal antibody specific to PDEF was raised and reacted with
      tissue microarrays consisting of benign breast, in situ ductal, invasive ductal,
      and invasive lobular breast carcinomas. The antibody was also reacted with tissue
      microarrays, including benign prostate, prostate intraepithelial neoplasias
      (PINs), and prostate carcinomas. Increased expression of PDEF was identified in
      18%, 50%, 46%, and 51% of benign breast tissues, intraductal, invasive ductal,
      and invasive lobular carcinomas, respectively. Importantly, in matched samples of
      benign breast vs tumor, 90% showed higher expression of PDEF in the tumor tissue.
      Moreover, in invasive breast carcinomas, increased PDEF expression tended to
      correlate with Her2/neu overexpression. Increased expression of PDEF was also
      found in 27%, 33%, and 40% of benign prostate tissues, PIN samples, and prostate
      adenocarcinomas, respectively. Again, in matching samples of cancer vs benign and
      cancer vs PIN, 68% and 70%, respectively, showed increased expression in the
      malignant tissue. Moreover, PDEF was found to be more highly expressed in tumors
      with intermediate or high Gleason score compared with low-grade tumors (P < .01).
      In addition, R1881 treatment induced PDEF expression in the LNCaP prostate tumor
      cell line, suggesting regulation of PDEF by androgens in vivo. Together, these
      results for the first time show frequent increased expression of PDEF protein in
      breast and prostate tumors and support a role for PDEF in breast and prostate
      cancer progression.

PMID- 17521702
TI  - The Y-encoded TSPY protein: a significant marker potentially plays a role in the
      pathogenesis of testicular germ cell tumors.
AB  - The testis-specific protein Y-encoded (TSPY) gene is the putative gene for the
      gonadoblastoma locus on the Y chromosome (GBY) that predisposes dysgenetic gonads
      of intersex patients to gonadoblastoma development. TSPY is expressed at high
      levels in gonadoblastoma tissues, supporting its possible oncogenic function in
      this type of germ cell tumors. To explore the possibility that this Y chromosome
      gene is also involved in pathogenesis of the more common testicular germ cell
      tumors (TGCTs), we have conducted various expression studies using
      immunohistochemistry, Western blotting, and reverse transcription-polymerase
      chain reaction analysis on 171 cases of TGCTs and selected normal testis
      controls. Our results demonstrated that TSPY protein is abundantly expressed in
      the precursor, carcinoma in situ or intratubular germ cell neoplasia
      unclassified, and seminoma, but only minimally or not expressed in various types
      of nonseminomas. TSPY coexpresses with established germ cell tumor markers (such
      as placental-like alkaline phosphatase, c-KIT, OCT4) and proliferative markers
      (such as Ki-67 and cyclin B1) in the same tumor cells at both RNA and protein
      levels. Ectopic TSPY expression in cultured cells up-regulates progrowth genes,
      including those at chromosome 12p13, frequently gained/amplified in TGCTs. Our
      results suggest that TSPY, in combination with other markers, could be an
      important marker for diagnosis and subclassification of TGCTs and support its
      role in the pathogenesis of both gonadoblastoma and TGCTs.

PMID- 17521704
TI  - Craniomandibular morphology supporting the diphyletic origin of mangabeys and a
      new genus of the Cercocebus/Mandrillus clade, Procercocebus.
AB  - Previous studies have noted skeletal and dental differences supporting the
      diphyletic origin of the mangabeys. Documented postcranial and dental characters
      are congruent with molecular data and thus support a close relationship between
      Cercocebus and Mandrillus (mandrills and drills) on the one hand and Lophocebus,
      Papio (baboons), and Theropithecus (geladas) on the other. Most of these
      characters, however, are postcranial and difficult to assess in the papionin
      fossil record because associated material is rare. In order to assess the African
      papionin fossil record and determine the evolutionary history of this group,
      cranial characters are critical. Here, a set of craniomandibular morphologies are
      documented that support the diphyletic origin of the mangabeys and more broadly
      support the molecular African papionin clades (i.e., Cercocebus/Mandrillus vs.
      Lophocebus/Papio/Theropithecus). These characters are then used to identify a
      series of fossil crania from Taung as representative of a new member of the
      Cercocebus/Mandrillus clade, Procercocebus antiquus. Procercocebus antiquus is
      closest in morphology to the extant taxon Cercocebus torquatus, and a probable
      ancestor-descendant relationship between Procercocebus and Cercocebus is
      suggested. Paleoecological reconstructions also suggest that a predator-prey
      relationship between African crowned eagles and the Procercocebus-Cercocebus
      lineage has existed for approximately the last two million years. Implications
      for Cercocebus biogeography and evolution are discussed.

PMID- 17521703
TI  - Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular
      epithelioid cell neoplasms.
AB  - Angiomyolipoma (AML) belong to a family of tumors known as perivascular
      epithelioid cell tumors (PEComas) that share a common immunophenotypic profile of
      muscle and melanocytic differentiation. These tumors are clonal in nature and
      have a strong association with tuberous sclerosis. Genetic analyses have reported
      allelic imbalance at the TSC2 locus on 16p13. In the context of non-tuberous
      sclerosis complex (TSC), non-lymphangioleiomyomatosis-associated AMLs, and non
      renal PEComas, the functional status of the TSC2 signaling pathway has not been
      reported. Studies over the last several years have uncovered a critical role of
      the TSC1/2 genes in negatively regulating the Rheb/mTOR/p70S6K cascade. Here, we
      examined the activity of this pathway in sporadic AMLs and PEComas using
      immunohistochemical and biochemical analyses. We found increased levels of
      phospho-p70S6K, a marker of mTOR activity, in 15 of 15 non-TSC AMLs. This was
      accompanied by reduced phospho-AKT expression, a pattern that is consistent with
      the disruption of TSC1/2 function. Western blot analysis confirmed mTOR
      activation concurrent with the loss of TSC2 and not TSC1 in sporadic AMLs.
      Similarly, elevated phospho-p70S6K and reduced phospho-AKT expression was
      detected in 14 of 15 cases of extrarenal PEComas. These observations provide the
      first functional evidence that mTOR activation is common to sporadic, non-TSC
      related AMLs and PEComas. This suggests the possibility that mTOR inhibitors such
      as rapamycin may be therapeutic for this class of disease.

PMID- 17521705
TI  - Carbon and nitrogen isotopic compositions of particulate organic matter and
      biogeochemical processes in the eutrophic Danshuei Estuary in northern Taiwan.
AB  - The Danshuei Estuary is distinctive for the relatively short residence time (1-2
      d) of its estuarine water and the very high concentration of ammonia, which is
      the dominant species of dissolved inorganic nitrogen in the estuary, except near
      the river mouth. These characteristics make the dynamics of nitrogen cycling
      distinctively different from previously studied estuaries and result in unusual
      isotopic compositions of particulate nitrogen (PN). The delta(15)N(PN) values
      ranging from -16.4 per thousand to 3.8 per thousand lie in the lower end of
      nitrogen isotopic compositions (-16.4 to +18.7 per thousand) of suspended
      particulate matter observed in estuaries, while the delta(13)C values of
      particulate organic carbon (POC) and the C/N (organic carbon to nitrogen) ratios
      showed rather normal ranges from -25.5 per thousand to -19.0 per thousand and
      from 6.0 to 11.3, respectively. There were three major types of particulate
      organic matter (POM) in the estuary: natural terrigenous materials consisting
      mainly of soils and bedrock-derived sediments, anthropogenic wastes and
      autochthonous materials from the aquatic system. During the typhoon induced flood
      period in August 2000, the flux-weighted mean of delta(13)C(POC) values was -24.4
      per thousand, that of delta(15)N(PN) values was +2.3 per thousand and that of C/N
      ratio was 9.3. During non-typhoon periods, the concentration-weighted mean was 
      23.6 per thousand for delta(13)C(POC), -2.6 per thousand for delta(15)N(PN) and
      8.0 for C/N ratio. From the distribution of delta(15)N(PN) values of highly
      polluted estuarine waters, we identified the waste-dominated samples and
      calculated their mean properties: delta(13)C(POC) value of -23.6+/-0.7 per
      thousand, delta(15)N(PN) value of -3.0+/-0.1 per thousand and C/N ratio of 8.0+/
      1.4. Using a three end-member mixing model based on delta(15)N(PN) values and C/N
      ratios, we calculated contributions of the three major allochthonous sources of
      POC, namely, wastes, soils and bedrock-derived sediments, to the estuary. Their
      contributions were, respectively, 83%, 12% and 5% under non-typhoon conditions,
      and 9%, 63% and 28% under typhoon conditions. The autochthonous POM had the most
      varied isotopic compositions, encompassing the full ranges of delta(13)C(POC) (
      25.5 to -19.1 per thousand), delta(15)N(PN) (-16.4-3.8 per thousand) and C/N
      ratio (6.0-11.3). The heavy end of the carbon isotopic composition reflected the
      typical marine condition and the lower end the estuarine condition, which
      probably had elevated concentrations of dissolved inorganic carbon with low
      delta(13)C values due to input from decomposition of organic matter. The lack of
      isotopically heavy PN, as found in larger estuaries, was attributed to
      isotopically light starting materials, namely, anthropogenic wastes, the slow
      phytoplankton growth within the estuary and the rather short residence time; the
      latter two factors made (15)N enrichment during ammonia consumption very limited.
      The most isotopically light PN likely originated from phytoplankton incorporating
      (15)N-depleted nitrate near the river mouth, where ammonia inhibition of nitrate
      uptake probably stopped.

PMID- 17521706
TI  - Comparison of seven kinds of drinking water treatment processes to enhance
      organic material removal: a pilot test.
AB  - Organic matter in source water has presented many challenges in the field of
      water purification, especially for conventional treatment. A two-year-long pilot
      test comparing water treatment processes was conducted to enhance organic matter
      removal. The tested process combinations included the conventional process,
      conventional plus advanced treatment, pre-oxidation plus conventional process and
      pre-oxidation plus conventional plus advanced treatment. The efficiency of each
      kind of process was assayed with the comprehensive indices of COD(Mn), TOC,
      UV(254), AOC, BDOC, THMs, and HAAs and their formation potential. The results
      showed that the combination of the conventional process and O(3)-BAC provides
      integrated removal of organic matter and meets the required standards. It is the
      best performing treatment tested in this investigation for treating polluted
      source water in China. Moreover, much attention should be paid to organic removal
      before disinfection to control DBP formation and preserve biostability. This
      paper also reports the range of efficiency of each unit process to calculate the
      total efficiency of different process combinations in order to help choose the
      appropriate water treatment process.

PMID- 17521707
TI  - Development and application of a multi-channel monitoring system for near real
      time VOC measurement in a hazardous waste management facility.
AB  - This paper describes the development and application of a multi-channel
      monitoring system for recording, processing, and analyzing volatile organic
      compound (VOC) levels discharged to the atmosphere from a walk-in hood in a
      hazardous waste management facility. The monitoring system consists of an array
      of PID (photo ionization detector) sensors and a networked control program that
      provides operational schematic diagram, performs data analyses, and illustrates
      real-time graphical displays. Furthermore, the system records potential worker
      exposures, exhaust filtration efficiency and environmental release levels. Multi
      channel continuous monitoring of VOCs is successfully implemented during chemical
      bulking operations. It is shown that a real-time monitoring system is effective
      for early warning detection of hazardous chemicals and for predicting the
      performance of adsorption filters used for VOC removal. In addition, a connected
      local weather visualization system supports efforts to minimize potential health
      and environmental impacts of VOC emissions to surrounding areas.

PMID- 17521708
TI  - Effects of personal particulate matter on peak expiratory flow rate of asthmatic
      children.
AB  - Many researches have shown that the particulate matter (PM) of air pollution
      could affect the pulmonary functions, especially for susceptible groups such as
      asthmatic children, where PM might decrease the lung function to different
      extents. To assess the effects of PM on health, most studies use data from
      ambient air monitoring sites to represent personal exposure levels. However, the
      data gathered from these fixed sites might introduce certain statistical
      uncertainties. The objectives of this study are to evaluate the effects of
      various size ranges of PM on peak expiratory flow rate (PEFR) of asthmatic
      children, and to compare the model performance of using different PM measurements
      (personal exposures versus fixed-site monitoring) in evaluation. Thirty asthmatic
      children, aged 6 to 12 years, who live near the fixed monitoring site in Sin
      Chung City, Taipei County, Taiwan, were recruited for the study. Personal
      exposures to PM(1), PM(2.5), and PM(10) were measured continuously using a
      portable particle monitor (GRIMM Mode 1.108, Germany). In addition, an activity
      diary and questionnaires were used to investigate possible confounding factors in
      their home environments. The peak expiratory flow rate of each participant was
      monitored daily in the morning and in the evening for two weeks. Results showed
      several trends, although not necessarily statistically significant, between
      personal PM exposures and PEFR measurements in asthmatic children. In general,
      notable findings tend to implicate that not only fine particles (PM(2.5)) but
      also coarse particles (PM(2.5-10)) are likely to contribute to the exacerbation
      of asthmatic conditions. Stronger lagged effect and cumulative effect of PM on
      the decrements in morning PEFR were also found in the study. Finally, results of
      linear mixed-effect model analysis suggested that personal PM data was more
      suitable for the assessment of change in children's PEFR than ambient monitoring
      data.

PMID- 17521709
TI  - Decreased levels of PAI-1 and alpha 2-antiplasmin contribute to enhanced
      fibrinolytic activity in divers.
AB  - BACKGROUND: There are a number of reported cases of decompression sickness (DCS)
      with haemorrhages. These cases have not been sufficiently investigated and thus
      bleeding complications could not be directly correlated to the enhanced
      fibrinolysis. OBJECTIVES: The effect of hyperbaric exposition and decompression
      on the main components of fibrinolytic system has been measured. METHODS: Two
      groups of 25 male divers each were subjected to hyperbaric exposures to the
      pressure of either 400 kPa - group I - or 700 kPa - group II followed by a staged
      decompression. The divers were monitored for clinical symptoms of DCS and checked
      for Doppler-detected venous gas bubbles. Venous blood was drawn from divers
      before exposition and 15 min after decompression. The concentrations and
      activities of t-PA and PAI-1 as well as concentrations of PAP and alpha2
      antiplasmin and activity of factor XIIa were measured. RESULTS: In all groups of
      divers no cases of DCS as well as detectable gas bubbles were noted. We observed
      elevated concentration of PAP, decreased concentration of alpha2-AP, decreased
      PAI-1 concentration and activity. There were no significant changes in factor
      XIIa activity as well as of t-PA concentration and activity. CONCLUSIONS:
      Hyperbaric exposition and decompression induce activation of fibrinolysis, even
      in the absence of detectable gas bubbles. Fibrinolytic activity increases mainly
      due to decrease of PAI-1 concentration and activity. Further clinical trials are
      necessary for the estimation of the importance of activation of fibrinolysis with
      decreased level of PAI-1 and alpha2-AP as a possible risk factor for bleeding in
      divers.

PMID- 17521710
TI  - CX3CR1 receptor is up-regulated in monocytes of coronary artery diseased
      patients: impact of pre-inflammatory stimuli and renin-angiotensin system
      modulators.
AB  - Fractalkine/CX3CR1 pathway is considered a major modulator of atherosclerosis. In
      the present study, expression of CX3CR1 on PBMCs/monocytes of healthy individuals
      and coronary artery diseased patients was initially assessed by flow cytometry.
      Effects of pre-inflammatory cytokines interferon (INF)-gamma and tumor necrosis
      factor (TNF)-alpha on expression of CX3CR1 and a single representative of each
      major chemokine family (CCR5 and CXCR4) were further assessed in three cell
      models: THP-1 monocytes, Jurkat T lymphocytes and primary monocytes isolated from
      healthy donors. Finally, effects of angiotensin-converting enzyme (ACE)
      inhibitors captopril, lisinopril and angiotensin receptor blocker (ARB) losartan
      on chemokine receptor expression were evaluated in the same cell models either in
      a naive or stimulated state. INF-gamma significantly affected the chemokine
      receptor phenotype of THP-1 cells by increasing the rate of CX3CR1-positive
      cells. Pre-treatment with the ACE inhibitors, captopril and lisinopril, and the
      ARB, losartan, did not influence these effects. Captopril and lisinopril
      similarly had no effect on either stimulated or naive primary monocytes. Yet, a
      small but repeatable increase in CX3CR1 expression after treatment with losartan
      was noted. Nevertheless, the latter observation did not retain statistical
      significance after applying the Bonferroni correction. In conclusion, our data
      did not indicate any significant effect of the ACE inhibitors on the chemokine
      receptor phenotype of monocytes.

PMID- 17521711
TI  - Evaluation of reticulated platelets in patients with sickle cell diseases.
AB  - BACKGROUND AND PURPOSE: Reticulated platelet (RP) count provides an estimate of
      thrombopoiesis. The objective was to evaluate RP in patients in different stages
      of sickle cell disease (SCD) and to determine the relationship between
      interleukin-6 (IL-6), interleukin-3 (IL-3) and thrombopoietin (TPO) and RP count
      and degree of activation. METHODS: Eighty-nine adult patients with SCD were
      studied: 38 were in the steady state, 27 in hemolytic crisis (HC) and 24 in vaso
      occlusive crisis (VOC). RPs and activated platelets were analyzed by flow
      cytometry. Soluble P-selectin, IL-6, IL-3 and thrombopoietin (TPO) levels were
      measured by ELISA tests. RESULTS: The patients in VOC had a higher absolute
      number of RPs and CD62P+ platelets than did the control group or patients in the
      steady state. A significant correlation was observed between the absolute number
      of CD62P+ platelets and RPs in patients in the steady state, HC and VOC. In the
      steady-state group of patients, the level of soluble P-selectin was found to be
      dependent on the RP values. IL-3 and TPO serum levels were higher in patients in
      the steady state, HC and VOC than in the control group. IL-6 serum levels were
      higher in HC and VOC patients than in the control group and higher in patients in
      the steady state than in the VOC group. CONCLUSION: Our results suggest that PRs
      contribute to the vaso-occlusive process in sickle cell disease. Increased
      interleukin serum levels probably indicate that inflammatory process is involved
      in the vascular-occlusive phenomenon. However, it appears that these inflammatory
      mediators do not have an effect on thrombopoiesis in sickle-cell-disease
      patients.

PMID- 17521712
TI  - Soluble CD40 ligand:interleukin-10 ratio predicts in-hospital adverse events in
      patients with ST-segment elevation myocardial infarction.
AB  - INTRODUCTION: The balance between pro-inflammatory and anti-inflammatory
      molecules is likely to modulate the processes that lead to atherogenesis and
      rapid coronary artery disease progression. We sought to compare the positive
      predictive values of serum soluble CD40 ligand (sCD40L)/interleukin-10 (IL-10)
      ratio, versus individual sCD40L, and IL-10 measurements regarding in-hospital
      events in patients admitted into the hospital with ST-segment elevation
      myocardial infarction (STEMI). METHODS: We recruited 96 patients with STEMI.
      sCD40L and IL-10 were measured at hospital admission in every patient. The
      composite of in-hospital death and heart failure represented the study end-point.
      Heart failure was defined as Killip class>1. Multivariable logistic regression
      analysis was performed to identify independent variables related to in-hospital
      events. RESULTS: Thirty two patients (33%) achieved the study end-point and 64
      (67%) had no adverse events during hospital admission. IL-10 levels (pg/ml) were
      lower (28.2+/-9.8 versus 33.24+/-11.3, p=0.03) and sCD40L levels (pg/ml) higher
      (156.8+/-54.2 versus 135.4+/-38.70, p=0.02) in patients with events compared to
      those without events. Significantly higher odd ratios were found for sCD40L/IL-10
      ratio (OR=2.10, 95% CI: 1.90 to 2.80, p=0.01) compared to individual sCD40L
      (OR=1.40, 95% CI: 0.90 to 2.20, p=0.08) and IL-10 (OR=0.70, 95% CI: 0.50 to 0.93,
      p=0.02) measurements. CONCLUSION: Our study showed that serum ratio of sCD40L/IL
      10 is a better independent predictor of in-hospital adverse events than
      individual sCD40L and IL-10 measurements in patients with STEMI.

PMID- 17521713
TI  - Is EGFR a moving target during radiotherapy of carcinoma of the uterine cervix?
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) is frequently
      overexpressed in uterine cervix carcinoma. The role of the pre-treatment EGFR
      expression levels and the changes of expression induced by ionizing radiation
      (IR) have not been conclusively defined. PATIENTS AND METHODS: The staining
      intensity (SI) and labeling index (LI) of EGFR were determined in 38 patients by
      immunohistochemistry (IHC). Biopsies were taken before after 1 week of RT. EGFR
      expression was correlated with cell cycle, apoptosis and angiogenesis. RESULTS:
      Before RT, 87% and after 1 week of RT, 95% of samples were positive for EGFR
      (p=0.2). Two patterns were observed, either increasing or decreasing expression
      after initiating RT. An increase of the EGFR SI was seen in 63% of patients from
      a mean of 57 SI (SD+/-60) before RT to 142 SI (SD+/-80.8) (p=0.001) during RT. In
      32% of cases, EGFR decreased from 165 SI before (SD+/-83.0) to 75 SI (SD+/-73.0)
      (p< or =0.001) during RT. Two of five (5%) patients negative for EGFR before RT
      remained negative. An increase of the RT-induced EGFR LI was associated with
      reduced microvessel density (MVD) (p=0.02). Changes of the EGFR LI did neither
      correlate with cell cycle arrest nor apoptosis. CONCLUSIONS: EGFR expression
      changes unpredictably during RT. The implications of changing EGFR during RT
      remain to defined. Repeated biopsies and EGFR reassessment during RT may help to
      better define EGFR-targeted treatment.

PMID- 17521714
TI  - An MR-compatible device for delivering smoked marijuana during functional
      imaging.
AB  - Smoking is the preferred method of administration for two of the most frequently
      abused drugs, marijuana and nicotine. The high temporal and spatial resolution of
      functional magnetic resonance imaging (fMRI) make it a natural choice for
      studying the neurobiological effects of smoked drugs if the challenges of smoking
      in a magnetic resonance (MR) scanner can be overcome. We report on a design for
      an MR-compatible smoking device that can be used for smoking marijuana (or
      tobacco) during fMRI examinations. Nine volunteers smoked marijuana cigarettes
      (3.51% Delta9-THC) on two occasions: with and without the device. The device
      allowed subjects to smoke while they lay in the scanner, while containing all
      smoke and odors. Plasma Delta9-THC, subjective reports of intoxication, and heart
      rate increases are reported, and were all similar in individuals smoking
      marijuana either with or without the device. The use of this device will help
      advance research studies on smoked drugs including marijuana, tobacco and crack
      cocaine.

PMID- 17521715
TI  - The impact of the opioids fentanyl and morphine on nociception and bone
      destruction in a murine model of bone cancer pain.
AB  - Chronic pain resulting from metastasis into skeleton of certain neoplastic
      diseases remains poorly understood and relatively resistant to analgesic
      treatment. Opioids are the principal axis in drug therapy for this type of pain,
      especially at the end stage of cancer. Our aim was to examine whether, fentanyl
      as well as morphine, two potent analgesic opioids commonly used to treat cancer
      pain, would inhibit pain and bone lesion-related responses in a murine model of
      bone cancer pain. Repeated administration of equianalgesic doses of fentanyl
      (0.16 mg/kg s.c. once a day) and morphine (20 mg/kg s.c. once a day) initiated at
      day 1 (prophylactic treatment) or at day 7 (curative treatment) after tumor cell
      inoculation in the femoral cavity consistently decreased bone pain symptoms and
      tumor growth-induced bone destruction (micro-CT bone structure parameters). Both
      fentanyl and morphine treatments resulted in clear antinociceptive properties as
      well as reductions in cancer cell-induced bone lesions. The present results
      demonstrate that fentanyl, and to some lesser degree morphine, has potential
      benefits in the treatment and development of bone cancer pain. As such, chronic
      administration of high doses of certain opioids like fentanyl may have clinical
      utility in the management of bone cancer pain.

PMID- 17521716
TI  - Acute ischemic stroke: overview of major experimental rodent models,
      pathophysiology, and therapy of focal cerebral ischemia.
AB  - Ischemic stroke is a devastating disease with a complex pathophysiology. Animal
      modeling of ischemic stroke serves as an indispensable tool first to investigate
      mechanisms of ischemic cerebral injury, secondly to develop novel antiischemic
      regimens. Most of the stroke models are carried on rodents. Each model has its
      particular strengths and weaknesses. Mimicking all aspects of human stroke in one
      animal model is not possible since ischemic stroke is itself a very heterogeneous
      disorder. Experimental ischemic stroke models contribute to our understanding of
      the events occurring in ischemic and reperfused brain. Major approaches developed
      to treat acute ischemic stroke fall into two categories, thrombolysis and
      neuroprotection. Trials aimed to evaluate effectiveness of recombinant tissue
      type plasminogen activator in longer time windows with finer selection of
      patients based on magnetic resonance imaging tools and trials of novel
      recanalization methods are ongoing. Despite the failure of most neuroprotective
      drugs during the last two decades, there are good chances to soon have effective
      neuroprotectives with the help of improved preclinical testing and clinical trial
      design. In this article, we focus on various rodent animal models, pathogenic
      mechanisms, and promising therapeutic approaches of ischemic stroke.

PMID- 17521717
TI  - Socioeconomic status as an independent predictor of physiological biomarkers of
      cardiovascular disease: evidence from NHANES.
AB  - BACKGROUND: C-reactive protein, homocysteine, cholesterol, and fibrinogen are
      known to vary by socioeconomic status (SES). Using a nationally representative
      study, we examined whether these factors vary independently of all other known
      risk factors, such as diet, exercise, and genetic predisposition. METHODS: We
      analyzed the 1999-2002 National Health Examination and Nutrition Survey using
      logistic regression models. RESULTS: We found that high-density lipoprotein
      cholesterol blood levels increase with income and educational attainment after
      controlling all known risk factors for elevated cholesterol (e.g., diet,
      exercise, and family history). Blood levels of C-reactive protein are inversely
      associated with income and education. Homocysteine blood levels are inversely
      associated with income even after controlling for blood folate level. A non
      significant inverse relationship between homocysteine levels and educational
      attainment was also observed. Blood levels of low-density lipoprotein cholesterol
      and fibrinogen were not significantly associated with income or education.
      CONCLUSIONS: Levels of "good" (high density lipoprotein) cholesterol increase
      with income and education even after controlling for factors known to place
      people at risk of high cholesterol. Stress differences by social class may play a
      role.

PMID- 17521719
TI  - Systemic mastocytosis in association with chronic lymphocytic leukemia: a rare
      diagnosis.
AB  - Systemic mastocytosis may be primary or be associated with other hematological
      malignancies, most commonly myeloid neoplasms. In contrast, the association of
      systemic mastocytosis with lymphoid neoplasms is comparatively rare, and in the
      absence of appropriate clinical vigilance the diagnosis may be missed. We report
      a case of aggressive systemic mastocytosis associated with chronic lymphocytic
      leukemia (SM-CLL), placing particular emphasis on the investigational algorithm
      used in establishing this diagnosis, and discussing key clinical considerations
      in the initiation of therapy.

PMID- 17521718
TI  - Role of plasma fibronectin in the foreign body response to biomaterials.
AB  - Host responses to biomaterials control the biological performance of implanted
      medical devices. Upon implantation, synthetic materials adsorb biomolecules,
      which trigger an inflammatory cascade comprising coagulation, leukocyte
      recruitment/adhesion, and foreign body reaction. The foreign body reaction and
      ensuing fibrous encapsulation severely limit the in vivo performance of numerous
      biomedical devices. While it is well established that plasma fibrinogen and
      secreted cytokines modulate leukocyte recruitment and maturation into foreign
      body giant cells, mediators of chronic inflammation and fibrous encapsulation of
      implanted biomaterials remain poorly understood. Using plasma fibronectin (pFN)
      conditional knock-out mice, we demonstrate that pFN modulates the foreign body
      response to polyethylene terephthalate disks implanted subcutaneously. Fibrous
      collagenous capsules were two-fold thicker in mice depleted of pFN compared to
      controls. In contrast, deletion of pFN did not alter acute leukocyte recruitment
      to the biomaterial, indicating that pFN modulates chronic fibrotic responses. The
      number of foreign body giant cells associated with the implant was three times
      higher in the absence of pFN while macrophage numbers were not different,
      suggesting that pFN regulates the formation of biomaterial-associated foreign
      body giant cells. Interestingly, cellular FN (cFN) was present in the capsules of
      both normal and pFN-depleted mice, suggesting that cFN could not compensate for
      the loss of pFN. These results implicate pFN in the host response to implanted
      materials and identify a potential target for therapeutic intervention to enhance
      the biological performance of biomedical devices.

PMID- 17521720
TI  - Increased Rac activity is required for the progression of T-lymphomas induced by
      Pten-deficiency.
AB  - Mutation of the tumor suppressor PTEN results in loss of its PI3-kinase
      counteracting function. PI3-kinase stimulates tumor formation by PKB/Akt-mediated
      cell proliferation and prevention of apoptosis. PI3-kinase may also activate Rho
      GTPases and their regulatory GEFs to promote invasion. Here we have analyzed the
      function of the Rac-specific activator, Tiam1, in PI3-kinase-induced T
      lymphomagenesis. Mice with a T cell-specific Pten deletion developed T-lymphomas
      with enhanced PKB/Akt phosphorylation. However, these T-lymphomas infiltrated
      more frequently into various organs in Tiam1-deficient mice compared to wild type
      mice. Surprisingly, Tiam1-deficient lymphomas showed increased Rac activity,
      suggesting that the lack of Tiam1 is compensated by alternative Rac-activating
      mechanisms that lead to increased progression of PI3-kinase-induced T-lymphomas.

PMID- 17521721
TI  - Adenosine arrests apoptosis in lymphocytes but not in phagocytes from primary
      leucocyte cultures of the teleost fish, Sparus aurata L.
AB  - Adenosine (A) and its derivatives have important biological functions, including
      the inhibition of immune responses and apoptosis induction. The aim of this work
      was to investigate whether A and N(6)-cyclohexyladenosine (CHA) regulate
      apoptosis in leukocyte cultures from the teleost, gilthead seabream (Sparus
      aurata L.) by flow cytometry using a double fluorescence staining method. Head
      kidney leukocytes (HKLs) were cultured for 0, 24 or 48h. The kinetics of
      FDA(+)/PI(-) (viable), FDA(-)/PI(-) (apoptotic) and FDA(-)/PI(+) (necrotic)
      leukocyte subpopulations were followed during the culture process. Apoptosis was
      induced by addition of resveratrol or staurosporine to the culture media and the
      study was validated by transmission electron microscopy. A and CHA did not induce
      but decreased apoptosis of seabream HKLs, in particular HK lymphocytes (L), after
      24h in culture. Results raise the question whether apoptosis is differently
      modulated by purine nucleosides in fish L and phagocytes and also in fish
      compared to mammalian cells.

PMID- 17521722
TI  - The incC korB region of RK2 repositions a mini-RK2 replicon in Escherichia coli.
AB  - Analysis by fluorescence microscopy has established that plasmid RK2 in
      Escherichia coli and other gram-negative bacteria is present as discrete clusters
      that are located inside the nucleoid at the mid- or quarter-cell positions. A
      mini-RK2 replicon containing an array of tetO repeats was visualized in E. coli
      cells that express a TetR-EYFP fusion protein. Unlike intact RK2, the RK2 mini
      replicon (pCV1) was localized as a cluster at the cell poles outside of the
      nucleoid. Insertion of the O(B1)incC korB partitioning (par) region of RK2 into
      pCV1 resulted in a shift of the mini-replicon to within the nucleoid region at
      the mid- and quarter-cell positions. Despite the repositioning of the mini-RK2
      replicon to the cellular positions where intact RK2 is normally located, the
      insertion of the intact O(B1) incC korB region did not significantly stabilize
      the mini-RK2 plasmid during cell growth. Deletions within the O(B1)incC or the
      korB region resulted in a failure of this par region to move pCV1 out of its
      polar position. The insertion of the par system of plasmid F into pCV1 resulted
      in a similar shift in the location of pCV1 to the nucleoid region. Unlike
      O(B1)incC korB, the insertion of the RK2 parABC resolvase system into pCV1 did
      not affect the polar positioning of pCV1. This effect of O(B1)incC korB on the
      location of pCV1 provides additional evidence for a partitioning role of this
      region of plasmid RK2. However, the failure of this region to significantly
      increase the stability of the mini-RK2 plasmid indicates that the localization of
      the plasmid to the mid- and quarter cell positions in E. coli is not in itself
      sufficient for the stable maintenance of plasmid RK2.

PMID- 17521723
TI  - Sequence analysis and characterizations of two novel plasmids isolated from
      Thermus sp. 4C.
AB  - Two novel plasmids, named pS4C and pL4C, were isolated from the thermophilic
      bacterium Thermus sp. 4C. The pS4C with a length of 5015bp and 58.25% of G+C
      content, contains 9 putative open reading frames (ORFs). The larger plasmid,
      pL4C, consisting of 21,248bp, has a G+C content of 68.60% and 34 putative ORFs.
      Both plasmids encode their own replication protein. The ORF 22 of pL4C and the
      ORF 4 of pS4C encode proteins with high sequence similarities to integrase (97%)
      and transposase (97%), respectively, which are both involved in DNA rearrangement
      and exchange. Furthermore, sequence analysis of pL4C also showed that several
      plasmid-encoded genes may be involved in DNA modification and repair, such as DNA
      G:T-mismatch repair endonuclease and micrococcal nuclease-like protein. These
      proteins may be involved in raising the repair efficiency and other minor editing
      needs. Interestingly, the elimination of plasmids significantly lowered the
      growth temperature of Thermus sp. 4C. Few reports dealing with the DNA repair
      enzymes on the plasmid from Thermus strains were published so far.

PMID- 17521724
TI  - Na(+) regulation by combined nitrogen in Azolla pinnata-Anabaena azollae
      symbiotic association during salt toxicity.
AB  - To study the regulation of Na(+) ion by combined-N sources in Azolla pinnata
      Anabaena azollae, Na(+) influx, intracellular Na(+) and Na(+) efflux were
      investigated in the presence of different N-sources (N(2), NH(4)(+), NO(3)(-) and
      urea) and various NaCl concentrations. Sodium influx by Azolla pinnata fronds was
      minimum in the presence of NO(3)(-). Almost identical levels of intracellular
      sodium, although less than N(2) and NH(4)(+) incubated fronds were observed in
      the presence of NO(3)(-) and urea. Efflux of sodium was minimum in urea and
      NO(3)(-) grown fronds. A low residual sodium was observed in the fronds incubated
      in NO(3)(-) and urea supplemented media. Results suggest that nitrate and urea
      curtailed the entry of sodium, reduced salt toxicity maximally by maintaining the
      minimum level of sodium and also conserved energy due to slow influx and efflux
      of Na(+) within the fronds during salt shock and the process of adaptation.

PMID- 17521725
TI  - Assessment of toxicity of the untreated and treated olive mill wastewaters and
      soil irrigated by using microbiotests.
AB  - Hazard assessments based on two measures of toxicity were conducted for the
      untreated olive mill wastewaters (U), untreated olive mill wastewaters organic
      extract (UOE), treated olive mill wastewaters (T), treated olive mill wastewaters
      organic extract (TOE) and extracts of soils ferti-irrigated with untreated (SU)
      and with treated olive mill wastewaters (ST). The measures of toxicity were
      achieved by the determination of the bioluminescence inhibition percent (I(B)%)
      of Vibrio fischeri and by the growth inhibition (GI) of Bacillus megaterium,
      Pseudomonas fluorescens and Escherichia coli. A bioluminescence inhibition of V.
      fischeri of 100%, 100%, 65%, 47%, 46% and 30% were obtained with U, UOE, T, TOE,
      SU and ST respectively. Indeed, even diluted 24 times, a significant
      bioluminescence inhibition of 96% was obtained by U. However, only 30%
      bioluminescence inhibition was obtained by 24 times diluted T. Whereas, 24 times
      diluted, SU and ST did not show a bioluminescence inhibition (3% and 1%,
      respectively). The GI of B. megaterium, P. fluorescens and E. coli were,
      respectively, 93%, 72% and 100% by U; 100%, 80% and 100% by UOE; 70%, 60% and 89%
      by T; 63%, 54% and 68% by TOE; 39%, 27% and 43% by SU and 23%, 0% and 34% by ST.
      The incubation of U or T in the soil during four months reduced their toxicity by
      54% and 35%, respectively. As it was expected, the most resistant bacterium to
      OMW toxicity is P. fluorescens then B. megaterium and E. coli. V. fischeri
      remained the most sensitive strain to the toxicity of this sewage what proves
      again its utilisation as standard of measure of the toxicity.

PMID- 17521726
TI  - Evaluation of colostral immunity in swine with commercial anti-leptospira
      polyvalent whole-bacteria vaccine.
AB  - The intensity and duration of passive immunity against swine leptospirosis were
      investigated by the microscopic agglutination test and in vitro leptospira growth
      inhibition. Twenty-one females at first parturition were divided into three
      groups: Group A (n=08): received two doses with 30 days interval of the
      commercial anti-leptospira bacterin A. Group B (n=06) received two doses with 30
      days interval of the commercial anti-leptospira bacterin B and Group C (n=07) was
      the control. In all groups the colostrums were collected. Blood collection of
      piglets was performed in four different ages. Agglutinin antibodies were equally
      detected in sera and colostrums for serovars Canicola, Grippotyphosa,
      Copenhageni, Icterohaemorrhagiae and Pomona (Group A) and Canicola, Copenhageni,
      Icterohaemorrhagiae, Pomona and Hardjo (Group B). Mean neutralizing antibodies
      titers were low. Passive immunity was low duration.

PMID- 17521727
TI  - Environmental management of pesticidal POPs in China: past, present and future.
AB  - China, the largest developing country in the world, has been undergoing rapid
      economic growth in the past two decades. Synchronously, large quantities of
      persistent organic chlorinated pesticides have been used in agriculture and non
      agriculture areas. Accompanying with incomplete management framework, the
      improper use and disposal of pesticides have caused serious pollution problems.
      In this study, we discussed: (1) ten persistent organochlorine pesticides in
      terms of historical production, consumption and number of manufacturers, import
      and export; (2) the current management framework of pesticidal persistent organic
      pollutants (POPs) with respect to legal system and government administrative
      system; (3) the existing problems in the management of pesticidal POPs; and
      proposed recommendations for countermeasures. Based on the available information,
      it can be concluded that records on the historical production and consumption
      quantities of pesticidal POPs are incomplete which makes a difficulty in the
      management. Although China has come a long way in developing a modern legal
      system, the current system is still considered weak and inefficient; and many
      challenges are ahead. The government administrative system has also been reformed
      and improved, but over-lapping jurisdictions still exist and are ineffective in
      managing pesticidal POPs program. To address these existing problems in
      pesticidal POPs management, it was suggested that more investigations should be
      conducted to collect information on pollution sources of pesticidal POPs, to
      evaluate their environmental risks, to identify new alternative chemicals and to
      complete management framework of pesticidal POPs in China. Furthermore, the
      public should be encouraged to participate in managing hazardous pesticidal POPs
      in China, and international cooperation and communication should be established
      and strengthened imperatively as well.

PMID- 17521728
TI  - Mechanism of adjuvant activity of cationic liposome: phosphorylation of a MAP
      kinase, ERK and induction of chemokines.
AB  - Cationic liposome has been effectively used as a delivery system for DNA and
      protein vaccines. Recently, we discovered that strong anti-tumor immunity could
      be generated when a peptide antigen (E7) was incorporated into 1,2-dioleoyl-3
      trimethylammonium-propane (chloride salt) (DOTAP) cationic liposome. Therefore,
      DOTAP liposome exhibits not only efficient delivery capacity, but also a potent
      adjuvant activity. In this report, the molecular mechanism of the adjuvanticity
      was studied both in vitro and in vivo. Microarray of mRNA analysis demonstrated
      that several chemokine genes are up-regulated by DOTAP liposome, including CCL2,
      CCL3 and CCL4, upon treatment of dendritic cells (DC) with DOTAP liposomes. CCL2
      induction was mediated through extracellular-signal-regulated kinase (ERK)
      pathway, demonstrated by specific inhibitors of ERK pathway and siRNA approaches.
      Furthermore, DOTAP-induced CCL2 expression is negatively regulated by the p38
      pathway. Consistently, ERK activation by DOTAP is also negatively regulated by
      p38. Moreover, PI-3 kinase was shown to be involved in both activation of ERK and
      induction of CCL2 by DOTAP. DOTAP- induced CCL2 release was also confirmed in the
      draining lymph nodes. More importantly, inhibition of ERK pathway completely
      abolishes the CCL2 accumulation in the draining lymph nodes and attenuates anti
      tumor activity of DOTAP/E7. In conclusion, DOTAP is an active lipid stimulator
      for DC resulting in ERK activation and CC chemokine induction. Our data
      elucidated one important mechanism of adjuvant activity of cationic liposome and
      could facilitate rational design of synthetic lipid based adjuvants.

PMID- 17521729
TI  - Protective DNA vaccination against myelin oligodendrocyte glycoprotein is
      overcome by C3d in experimental autoimmune encephalomyelitis.
AB  - Complement receptor 2 (CR2) and its physiological ligand, C3d, known for its
      molecular adjuvant property on the immune response, exhibit opposite effects with
      regard to autoimmunity. Although CR2 has been implicated in maintaining self
      tolerance, recent studies reported a role for C3d signaling to CR2 in tolerance
      breakdown to self-antigens and the initiation of inflammatory autoimmune
      pathologies. In the present study, we have investigated the effect of C3d in a
      model of tolerogenic DNA vaccination encoding the myelin oligodendrocyte
      glycoprotein (MOG-DNA) which protected mice from the induction of an experimental
      autoimmune encephalomyelitis (EAE). We show that fusing two or three copies of
      C3d to MOG overcomes the protective effect of DNA vaccination. Multimeric C3d was
      able to revert the unresponsiveness state of specific T cells induced by MOG-DNA,
      independently of a modification in the Th1/Th2 cytokine pattern. Interestingly,
      the adjuvant effect of C3d was not sufficient to boost the anti-MOG antibody
      response after DNA vaccination. These findings suggest that C3d might be involved
      in self-tolerance breakdown and could contribute to the pathogenesis of central
      nervous system autoimmune disorders.

PMID- 17521730
TI  - Cloning, expression and characterization of mugwort pollen allergen Art v 2, a
      pathogenesis-related protein from family group 1.
AB  - Mugwort (Artemisia vulgaris) belongs to the Compositae family, and is one of the
      main causes of allergy in late summer and autumn. The aim of the study was to
      characterize the allergen Art v 2 from mugwort pollen. Skin prick tests,
      performed in 19 patients allergic to mugwort and 10 control patients, showed an
      Art v 2 sensitization prevalence of 58%, whereas none false-positives were
      detected among control patients. Art v 2 was purified by standard chromatography
      and binding to Concanavalin A column and had an apparent molecular mass of 33 and
      20 kDa, calculated by gel permeation and SDS-PAGE under denaturing conditions,
      respectively, showing that the allergen is composed of two identical subunits.
      Art v 2-encoding cDNA was amplified by PCR using degenerate primers based on
      reported partial amino acid sequences. Cloned cDNA encoding Art v 2 contains 140
      bp that codify for a polypeptide of 15.8 kDa, with a predicted pI value of 5.2,
      and one potential N-glycosylation site. Protein homology search demonstrated that
      Art v 2 share 55-42% identical residues with pathogenesis-related protein PR-1 of
      tomato, potato, rape, wheat and rice. Homology was also found to Ves v 5 (41%
      identical residues). Bacterial-expressed recombinant Art v 2 was recognized only
      by 21% of mugwort-allergic patients. In conclusion, Art v 2 from mugwort is the
      first weed pollen allergen that belongs to the pathogenesis-related protein PR-1
      and its recombinant form could help molecular diagnosis of mugwort associated
      allergy.

PMID- 17521731
TI  - Alpha2 beta1 integrin signaling augments T cell receptor-dependent production of
      interferon-gamma in human T cells.
AB  - The mechanisms by which beta1 integrins modulate T cell costimulation are still
      poorly defined. In this study, we examined the role of collagen-binding integrins
      alpha1 beta1 and alpha2 beta1 in the regulation of interferon-gamma (IFN-gamma).
      We demonstrated that ligation of alpha2 beta1 integrin with Collagen type I (Coll
      I) but not alpha1 beta1 integrin with Collagen IV (Coll IV) significantly
      augmented T cell receptor (TCR)-dependent expression and production of IFN-gamma
      by effector T cells. The effect of Coll I was not due to cell adhesion as soluble
      Coll I also augmented TCR-dependent production of IFN-gamma. Inhibition studies
      indicated that activation of ERK and JNK MAPKs and PI3K/AKT are necessary for
      both TCR- and TCR+alpha2 beta1 integrin-dependent IFN-gamma production and that
      Coll I increases TCR-dependent activation of ERK and JNK MAPKs, and AKT. In
      addition, our results showed that Coll IV is less potent than Coll I in
      augmenting TCR-dependent activation of JNK/MAPK, which may explain the
      differential effect of collagen matrices on TCR-dependent IFN-gamma production.
      Together, these results indicate that the costimulatory effect of Coll I on IFN
      gamma expression is integrated at the levels of ERK and JNK MAPKs and PI3K/AKT
      signaling pathways and suggest JNK/MAPK as a major signaling pathway of Coll I
      costimulation. Thus, our study identifies alpha2 beta1 integrin as an important
      regulatory pathway of IFN-gamma expression and provides novel insights into the
      signaling mechanisms of integrin costimulation in T cells. As such, this study
      further supports the functional importance that Coll I interactions may have on
      the control of T cell-dependent Th1 inflammatory diseases.

PMID- 17521732
TI  - C-terminal LRRs of human Toll-like receptor 3 control receptor dimerization and
      signal transmission.
AB  - Toll-like receptor (TLR)3 recognizes dsRNA and activates the signaling cascade
      leading to production of IFN-beta via an adaptor protein, TICAM-1 (also called
      TRIF). The interface between ligand recognition and signal transduction by TLR3
      remains largely unknown. The crystalized ectodomain of human TLR3 revealed a
      horseshoe-shaped solenoid assembled from 23 leucine-rich repeats (LRRs). Here, we
      constructed LRR deletion mutants and tested the participation of each LRR in the
      IFN-inducing ability of TLR3. Only 3 of the 23 LRRs (LRR4, LRR11 and LRR17) were
      dispensable for the TLR3 function. Among the 20 dysfunctional mutants, LRR20- and
      LRR22-deleted mutants acted as dominant-negative inhibitors of wild-type TLR3.
      The LRR20-deleted mutant lost the poly(I:C)-binding ability, while LRR22-deleted
      mutant possessed it. Strikingly, the LRR21-deleted mutant functioned as a
      constitutively active form. These three mutants formed homodimers regardless of
      their different functional features and reacted with TLR3.7, a function-blocking
      anti-human TLR3 mAb whose epitope resided in LRR10-LRR16, suggesting that the
      intact conformation around the central solenoid was retained in the C-terminal
      mutants. These results suggest that the extracellular domains are a crucial
      trigger of cytoplasmic IFN signaling in TLR3. The altered molecular topology
      resulting from the deletion of LRR20, LRR21 or LRR22 critically affects the
      functional assembly of cytoplasmic TLR3, resulting in dysregulation of receptor
      receptor association and signal transmission from the outside ectodomain to the
      inside TIR domain.

PMID- 17521733
TI  - Molecular characterisation and expression of CD4 in two distantly related
      marsupials: the gray short-tailed opossum (Monodelphis domestica) and tammar
      wallaby (Macropus eugenii).
AB  - The gene and corresponding cDNA for CD4 in the gray short-tailed opossum,
      Monodelphis domestica, and the cDNA sequence for CD4 in the tammar wallaby,
      Macropus eugenii, have been characterised. The opossum CD4 homolog reveals
      conserved synteny, preserved genomic organisation and analogous structural
      arrangement to human and mouse CD4. Opossum and tammar CD4 exhibit typical
      eutherian CD4 features including the highly conserved p56(lck) binding motif in
      the cytoplasmic region and the invariant cysteine residues in extracellular
      domains 1 and 4. Interestingly, the marsupial CD4 sequences substitute a
      tryptophan for the first cysteine in domain 2 negating the formation of a
      disulphide bond as seen in other eutherian CD4 sequences except human and mouse.
      Overall the marsupial CD4 sequences share amino acid identity of 59% to each
      other and 37-41% with eutherian mammals. However, in contrast to eutherian
      homologs, the marsupial CD4 sequences were found to be truncated at the terminal
      end of the cytoplasmic tail. This is the first report confirming the presence of
      CD4 in a marsupial and describing its key features.

PMID- 17521734
TI  - Differential expression of new LTA splice variants upon lymphocyte activation.
AB  - Lymphotoxin alpha (LTA) is a member of the TNF cytokine superfamily, produced
      principally by lymphocytes. It plays an important role in immune and inflammatory
      responses. Many TNF superfamily members have functionally important isoforms
      generated by alternative splicing but alternative splicing of LTA has never been
      studied. The known LTA protein is encoded by a transcript containing four exons.
      Here we report seven new LTA splice variants, three of them evolutionary
      conserved. We demonstrate their presence in cytoplasmic RNA suggesting that they
      could be translated into new LTA isoforms. We observed that their expression is
      differentially regulated upon activation of peripheral blood mononuclear cells
      and lymphocyte subpopulations (CD4+, CD8+, and CD19+). Our data suggest that the
      new LTA splice variants might play a role in the regulation of the immune
      response.

PMID- 17521735
TI  - More than chemotaxis: a new anti-tumor DC vaccine modified by rAAV2-SLC.
AB  - Secondary lymphoid tissue chemokine (SLC) is strongly expressed in secondary
      lymphoid organs. Its ability to facilitate chemotaxis of both dendritic cells
      (DC) and T cells makes it a promising candidate for cancer therapy. In this
      study, we modified a BMDC vaccine by incorporating the SLC mature peptide gene.
      The efficacy of this vaccine was evaluated using a mouse hepatocellular carcinoma
      (HCC) model, with rAAV2 as the gene delivery vector. The rAAV2 encoding SLC
      (rAAV2-SLC) transfected immature BMDCs at high efficiency and the anti-tumor
      effects of SLC gene modified BMDCs (rAAV2-SLC/BMDC) were evaluated. In addition,
      rAAV2-SLC/BMDC vaccine injected directly into tumors attracted more CD4(+) and
      CD8(+) T lymphocytes into tumors and showed stronger anti-tumor effects than
      footpad delivery. Moreover, we found that the phenotypic expression of MHC II,
      the secretion of IL-12 and IFN-gamma, and T cell stimulation were increased in
      vitro following treatment with rAAV2-SLC/BMDC vaccine and these responses were
      inhibited by PTX. In vivo, PTX also inhibited the anti-tumor effects of the
      vaccine. The results suggest that the expression of SLC by rAAV2-SLC/BMDC plays
      more than a chemotactic role in anti-tumor responses, thus these studies further
      demonstrate that SLC has potential to be valuable in cancer therapy.

PMID- 17521736
TI  - Involvement of different nuclear hormone receptors in butyrate-mediated
      inhibition of inducible NF kappa B signalling.
AB  - BACKGROUND: NF kappa B plays a major role in the control of immune responses and
      inflammation. Recently, butyrate has not only been demonstrated to suppress NF
      kappa B activation in colorectal cancer cells, but also to modulate the activity
      and expression of the Peroxisome-Proliferator-Activated-Receptor gamma (PPAR
      gamma) and the vitamin D receptor (VDR). Therefore, we investigated a putative
      involvement of both receptors in butyrate-mediated inhibition of inducible NF
      kappa B signalling. RESULTS: Treatment of HT-29 cells with butyrate attenuated
      basal p50 as well as TNFalpha- and LPS-induced p50 and p65 NF kappa B dimer
      activity in the nucleus as measured by transcription factor assay. Cytosolic
      expression of I kappa B alpha protein was reduced by butyrate, and TNFalpha but
      not by LPS. Challenge of cells with the VDR antagonist ZK191732 up-regulated
      basal NF kappa B activity by decreasing I kappa B alpha simultaneously, while
      basal signalling was not influenced by the PPAR gamma inhibitor GW9662. Pre
      treatment with ZK191732 reduced the inhibitory effect of butyrate on NF kappa B
      activation caused by TNFalpha whereas no activation was noted in transfected
      dominant-negative PPAR gamma mutant vector cells. Adversely, the inhibitory
      effect of butyrate on NF kappa B activity induced by LPS was almost reversed in
      dominant-negative PPAR gamma mutant cells while pre-incubation of ZK191732 did
      not affect butyrate-mediated attenuation of LPS-induced NF kappa B signalling.
      CONCLUSION: These findings provide evidence for the involvement of the nuclear
      hormone receptors PPAR gamma and VDR in butyrate-mediated inhibition of inducible
      NF kappa B activation dependent on the stimulated signalling pathway. Moreover,
      VDR appears to play an inhibitory role in the regulation of basal NF kappa B
      signalling.

PMID- 17521737
TI  - Substrate specificity of copper-containing plant amine oxidases.
AB  - The steady-state kinetic parameters of the amine oxidases purified from Lathyrus
      cicera (LCAO) and Pisum sativum (PSAO) seedling were measured on a series of
      common substrates, previously tested on bovine serum amine oxidase (BSAO). LCAO,
      as PSAO, was substantially more reactive than BSAO with aliphatic diamines and
      histamine. The k(cat) and k(cat)/Km for putrescine were four and six order of
      magnitude higher, respectively. Differences were smaller with some aromatic
      monoamines. The plot of k(cat) versus hydrogen ions concentration produced bell
      shaped curves, the maximum of which was substrate dependent, shifting from
      neutral pH with putrescine to alkaline pH with phenylethylamine and benzylamine.
      The latter substrates made the site more hydrophobic and increased the pK(a) of
      both enzyme-substrate and enzyme-product adducts. The plot of k(cat)/Km versus
      hydrogen ion concentration produced approximately parallel bell-shaped curves.
      Similar pK(a) couples were obtained from the latter curves, in agreement with the
      assignment as free enzyme and free substrate pK(a). The limited pH dependence of
      kinetic parameters suggests a predominance of hydrophobic interactions.

PMID- 17521738
TI  - Molecular insights into nitrogenase FeMoco insertion--the role of His 274 and His
      451 of MoFe protein alpha subunit.
AB  - The final step of FeMo cofactor (FeMoco) assembly involves the insertion of
      FeMoco into its binding site in the molybdenum-iron (MoFe) protein of
      nitrogenase. Here we examine the role of His alpha274 and His alpha451 of
      Azotobacter vinelandii MoFe protein in this process. Our results from combined
      metal, activity, EPR, stability and insertion analyses show that mutations of His
      alpha274 and/or His alpha451, two of the histidines that belong to a so-called
      His triad, to small uncharged Ala specifically reduce the accumulation of FeMoco
      in MoFe protein. This observation indicates that the enrichment of histidines at
      the His triad is important for FeMoco insertion and that the His triad
      potentially serves as an intermediate docking point for FeMoco through transitory
      ligand coordination and/or electrostatic interaction.

PMID- 17521739
TI  - Do high doses of quinolones decrease the emergence of antibacterial resistance? A
      systematic review of data from comparative clinical trials.
AB  - OBJECTIVE: To evaluate whether the use of high doses of quinolones may reduce the
      development of antimicrobial resistance. DATA SOURCES: Relevant studies were
      identified from PubMed and the Cochrane Central Register of Controlled Trials
      (until June 2006). STUDY SELECTION AND DATA EXTRACTION: We performed a systematic
      review of the available data from comparative clinical studies reporting on the
      emergence of resistance when using different daily doses of quinolones. DATA
      SYNTHESIS: Twelve studies reported comparative data regarding the emergence of
      antimicrobial resistance. Development of resistance occurred in patients of 5/12
      studies included in the review, with no statistical difference between the
      compared arms. CONCLUSIONS: Although data from laboratory studies are indicative
      of a benefit from using high daily doses of quinolones in order to minimize the
      emergence of antimicrobial resistance, the data from the reviewed trials are
      limited and can neither support nor reject this finding. However, it seems that
      if a true benefit exists this is rather small and regards mainly isolates with
      initially high minimum inhibitory concentrations. Further comparative clinical
      studies focusing on this issue are justified.

PMID- 17521740
TI  - Environmental neurotoxic chemicals-induced ubiquitin proteasome system
      dysfunction in the pathogenesis and progression of Parkinson's disease.
AB  - Proteolytic degradation of unwanted proteins by the ubiquitin-proteasome system
      (UPS) is critical for normal maintenance of various cellular functions.
      Parkinson's disease (PD), one of the most prevalent neurodegenerative disorders,
      is characterized by prominent and irreversible nigral dopaminergic neuronal loss
      and intracellular protein aggregations. Epidemiological studies imply both
      environmental neurotoxins and genetic predisposition as potential risk factors
      for PD, though mechanisms underlying selective dopaminergic degeneration remain
      unclear. Studies with experimental PD models and postmortem PD brains have
      provided explicit evidence for mitochondria dysfunction and oxidative stress in
      PD pathogenesis. Recent identification of mutants in PINK1, DJ-1, Parkin, and
      LRRK-2 genes compliments the oxidative stress and mitochondrial dysfunction
      hypotheses in dopaminergic neuronal degeneration in PD. Mutants of alpha
      synuclein, Uch-L1 and Parkin support the involvement of UPS dysfunction in PD.
      Furthermore, various Parkinsonian toxicants have been shown to impair
      mitochondrial function, redox balances, and to some extent protein degradation
      machinery. Because environmental exposure to various neurotoxic agents is
      considered a dominant risk for development of PD, the interrelationship between
      neurotoxicant exposures and UPS dysfunction must be clearly understood.
      Elucidation of this interrelationship will help clarify 2 areas: (i) whether UPS
      dysfunction in PD is a primary pathogenic factor leading to nigral neuronal death
      or if it simply occurs as a consequence of oxidative stress and mitochondrial
      dysfunction and (ii) the interaction of genes and environment in the acceleration
      of nigral dopaminergic degeneration by targeting UPS. We review the recent
      evidence for UPS deficits in dopaminergic degeneration triggered by neurotoxins.

PMID- 17521741
TI  - Vasopressors for cardiopulmonary resuscitation. Does pharmacological evidence
      support clinical practice?
AB  - Adrenaline (epinephrine) has been used for cardiopulmonary resuscitation (CPR)
      since 1896. The rationale behind its use is thought to be its alpha-adrenoceptor
      mediated peripheral vasoconstriction, causing residual blood flow to be diverted
      to coronary and cerebral circulations. This protects these tissues from ischaemic
      damage and increases the likelihood of restoration of spontaneous circulation.
      Clinical trials have not demonstrated any benefit of adrenaline over placebo as
      an agent for resuscitation. Adrenaline has deleterious effects in the setting of
      resuscitation, predictable from its promiscuous pharmacological profile. This
      article discusses the relevant pharmacology of adrenaline in the context of CPR.
      Experimental and clinical evidences for the use of adrenaline and alternative
      vasopressor agents in resuscitation are given, and the properties of an ideal
      vasopressor are discussed.

PMID- 17521742
TI  - Parent-reported suicidal behavior and correlates among adolescents in China.
AB  - BACKGROUND: Suicidal risk begins to increase during adolescence and is associated
      with multiple biological, psychological, social, and cultural factors. This study
      examined the prevalence and psychosocial factors of parent-reported suicidal
      behavior in Chinese adolescents. METHODS: A community sample of 1920 adolescents
      in China participated in an epidemiological study. Parents completed a structured
      questionnaire including child suicidal behavior, illness history, mental health
      problems, family history, parenting, and family environment. Multiple logistic
      regression was used for data analysis. RESULTS: Overall, 2.4% of the sample
      talked about suicide in the previous 6 months, 3.2% had deliberately hurt
      themselves or attempted suicide, and 5.1% had either suicidal talk or self-harm.
      The rate of suicidal behavior increased as adolescents aged. Multivariate
      logistic regression indicated that the following factors were significantly
      associated with elevated risk for suicidal behavior: depressive/anxious symptoms,
      poor maternal health, family conflict, and physical punishment of parental
      discipline style. LIMITATIONS: Suicidal behavior was reported by parents. No
      causal relationships could be made based on cross-sectional data. CONCLUSIONS:
      The prevalence rate of parent-reported suicidal behavior is markedly lower than
      self-reported rate in previous research. Depressive/anxious symptoms and multiple
      family environmental factors are associated with suicidal behavior in Chinese
      adolescents.

PMID- 17521743
TI  - Does early response predict outcome in psychotherapy and combined therapy for
      major depression?
AB  - BACKGROUND: To examine the predictive value of early response for final outcome
      of psychotherapy and combined therapy in major depression. METHODS: Mild- to
      moderately depressed patients were treated with either Short-Term Psychodynamic
      Supportive Psychotherapy (SPSP) (N=63) only, or combined with an antidepressant
      (N=127). Early response was defined as a reduction of more than 25% on the HAM-D
      17 after 2 months. Outcome was determined in terms of complete nonresponse and
      remission rates. Associations between early response and outcome were examined
      using logistic regression analysis. RESULTS: In SPSP, early nonresponse was
      clearly related to final nonresponse (OR=3.57). Nevertheless, remission was not
      predicted by early response, and 26% of the early nonresponders ultimately
      achieved remission. In combined therapy, both final nonresponse (OR 7.13) and
      remission (OR 3.66) were associated with early nonresponse. LIMITATIONS: In this
      study, SPSP was the only psychotherapy examined. The design did not provide
      feedback to the therapist of the independently measured depression score after
      two months. CONCLUSION: Although a number of early nonresponsive patients will
      achieve remission, this study points out that these patients are at risk factor
      for ultimate treatment failure. This could be an indication for clinicians to
      adapt their treatment strategy.

PMID- 17521744
TI  - Phonetic mismatch negativity predicts social skills acquisition in schizophrenia.
AB  - Neurobiological mechanisms for social skills acquisition in schizophrenia remain
      largely unknown. We investigated whether an electrophysiological index of
      cognitive function predicts the degree of training-related social skills
      improvement in schizophrenia. Thirteen patients with schizophrenia underwent
      assessment of mismatch negativity (MMN) event-related potentials, followed by
      participation in a 3-month social skills training. Larger right frontal/temporal
      MMN current density values elicited by across-phoneme change were significantly
      associated with individual degrees of improvement in total social skills scores
      as assessed by a structured role play test. Although preliminary, these results
      suggest that phonetic MMN could be an index of social skills acquisition in
      patients with schizophrenia.

PMID- 17521745
TI  - Evaluation of inflammation and immunity in cats with spontaneous parvovirus
      infection: consequences of recombinant feline interferon-omega administration.
AB  - Administration of recombinant feline interferon-omega (rFeIFN) has been proposed
      for the prophylaxis of canine and feline parvovirosis. In the present study, the
      influence of the administration of rFeIFN on blood markers of inflammation (alpha
      globulins, alpha(1)-acid glycoprotein) and immune system activation (gamma
      globulins, IgG, IgM, specific anti-feline parvovirus IgG or IgM) was evaluated in
      a cattery developing an outbreak of feline panleukopenia due to feline parvovirus
      (FPV) infection few days after initial administration of rFeIFN. Kittens (n=23)
      were injected with rFeIFN (1MU/kg subcutaneously, once a day for 3 days) and
      their blood parameters were compared with those of 17 untreated cats. Cats that
      survived the outbreak were vaccinated and re-sampled 1 month after the last
      rFeIFN administration. Time of emergence of clinical signs and survival rate were
      not significantly different between the two groups. Controls and treated cats
      surviving the infection had high levels of gamma-globulins, total- and anti-FPV
      specific IgGs, likely due to passive transfer of maternal immunity. Compared to
      controls, treated kittens had lower levels of alpha(1)-globulins and higher mean
      values of gamma-globulins and immunoglobulins. Data from samples collected after
      vaccination revealed a higher level of gamma-globulins, total- and anti-FPV
      specific IgGs in treated kittens, compared with controls, suggesting that rFeIFN
      stimulates antibody production. Based on this results, rFeIFN should be
      administered to the queen, to increase passive maternal immunity, or to kittens
      before introduction in a potentially contaminated environment.

PMID- 17521746
TI  - Toll-like receptor 3 (TLR3): a new marker of canine monocytes-derived dendritic
      cells (cMo-DC).
AB  - Toll-like receptors (TLRs) are a family of functionally important receptors for
      recognition of pathogen-associated molecular pattern (PAMP) since they trigger
      the pro-inflammatory response and upregulation of costimulatory molecules,
      linking the rapid innate response to adaptative immunity. In human leukocytes,
      TLR3 has been found to be specifically expressed in dendritic cells (DC). This
      study examined the expression of TLR3 in canine monocytes-derived DC (cMo-DC) and
      PBMC using three new anti-TLR3 mAbs (619F7, 722E2 and 713E4 clones). The non
      adherent cMo-DC generated after culture in canine IL-4 plus canine GM-CSF were
      labelled with the three anti-TLR3 clones by flow cytometry, with a strong
      expression shown for 619F7 and 722E2 clones. By contrast, TLR3 expression was low
      to moderate in canine monocytes and lymphocytes. These results were confirmed by
      Western blot using 619F7 and 722E2 clones and several polypeptide bands were
      observed, suggesting a possible cleavage of TLR3 molecule or different
      glycosylation states. In addition, TLR3 was detectable in immunocytochemistry by
      using 722E2 clone. In conclusion, this first approach to study canine TLR3
      protein expression shows that three anti-TLR3 clones detect canine TLR3 and can
      be used to better characterize canine DC and the immune system of dogs.

PMID- 17521747
TI  - Subtotal bipolar tonsillectomy does not decrease postoperative pain compared to
      total monopolar tonsillectomy.
AB  - OBJECTIVE: To determine whether a subtotal bovie tonsillectomy decreases
      postoperative pain following adenotonsillectomy. METHODS: A prospective,
      randomized, double-blinded clinical trial was undertaken at a University
      Pediatric Children's Hospital and included 39 otherwise healthy children, aged 2
      12 years, undergoing adenotonsillectomy. Patients were randomized to receive
      either a subtotal or total removal of the tonsils utilizing an electrocautery
      technique. The main outcome measures included a visual analog scale (VAS) at rest
      and while eating, time to take 100 cm(3) of fluid, throat, neck, and ear pain,
      quantity of liquids, activity level and incidence of emesis and retching.
      RESULTS: A repeated measures analysis using a repeated measures ANOVA failed to
      demonstrate a statistically significant impact with either treatment for VAS at
      rest or while eating (p=0.52 and 0.48, respectively). A repeated measures
      analysis did not show either procedure significantly affecting throat, neck or
      ear pain, or liquid quantity. Time to take 100 cm(3) liquids and the incidence of
      emesis or retching were found not to be statistically significantly different
      between the treatment groups. CONCLUSION: Subtotal tonsillectomy via an
      electrocautery technique does not reduce postoperative pain or improve outcome
      parameters. Subtotal tonsillectomy with this technique is not recommended for
      this patient population.

PMID- 17521748
TI  - Corticosterone fails to produce conditioned place preference or conditioned place
      aversion in rats.
AB  - RATIONALE: In some rats, the hormone corticosterone is reinforcing. High novelty
      seeking rats (high responders, HR) self-administered corticosterone at a much
      higher rate than low novelty-seeking rats (low responders, LR) do [Piazza PV,
      Deroche V, Deminiere JM, Maccari S, Le Moal M, Simon H, Corticosterone in the
      range of stress-induced levels possesses reinforcing properties: implications for
      sensation-seeking behaviors, Proc Natl Acad Sci USA 1993;90:11738-42]. While
      previous studies demonstrated that corticosterone reinforces nose poking in a
      self-administration paradigm, no studies to date have examined whether
      corticosterone is rewarding. OBJECTIVE: Using the conditioned place preference
      (CPP) paradigm, we examined the rewarding effects of corticosterone in HR and LR
      rats. METHODS: Male Sprague-Dawley rats were classified into HR and LR groups
      based on their locomotor activity in a novel environment. Subsequently,
      independent groups of HR and LR rats underwent CPP for corticosterone (0, 2.5 or
      10 mg/kg; i.p.) or cocaine (12 mg/kg; i.p). CPP for cocaine was used as a
      positive control. RESULTS: While cocaine produced a strong CPP in both HR and LR
      rats, corticosterone failed to produce either preference or aversion in both
      phenotypes. CONCLUSION: Corticosterone is neither rewarding nor aversive in
      either behavioral phenotype.

PMID- 17521749
TI  - Gait parameters of treadmill versus overground locomotion in mouse.
AB  - Many studies of interest in motor behaviour and motor impairment in mice use
      equally treadmill or track as a routine test. However, the literature in mammals
      shows a wide difference of results between the kinematics of treadmill and
      overground locomotion. To study these discrepancies, we analyzed the locomotion
      of adult SWISS-OF1 mice over a large range of velocities using treadmill and
      overground track. The use of a high-speed video camera combined with
      cinefluoroscopic equipment allowed us to quantify in detail the various space and
      time parameters of limb kinematics. The results show that mice maintain the same
      gait pattern in both conditions. However, they also demonstrate that during
      treadmill exercise mice always exhibit higher stride frequency and consequently
      lower stride length. The relationship of the stance time and the swing time
      against the stride frequency are still the same in both conditions. We conclude
      that the conflict related to the discrepancy between the proprioceptive,
      vestibular, and visual inputs contribute to an increase in the stride frequency
      during the treadmill locomotion.

PMID- 17521750
TI  - Role of the stage-regulated nucleoside transporter TbNT10 in differentiation and
      adenosine uptake in Trypanosoma brucei.

PMID- 17521751
TI  - Improved synchronous production of Plasmodium falciparum gametocytes in vitro.
AB  - The sexual stages of the Plasmodium falciparum life cycle are attractive targets
      for vaccines and transmission blocking drugs. Difficulties in culturing and
      obtaining large amounts of sexual stage P. falciparum parasites, particularly
      early stages, have often limited research progress in this area. We present a new
      protocol which simplifies the process of stimulating gametocytogenesis leading to
      improved synchronous gametocyte production. This new method can be adapted to
      enrich for early stage gametocytes (I and II) with a higher degree of purity than
      has previously been achieved, using MACS magnetic affinity columns. The protocol
      described lends itself to large scale culturing and harvesting of synchronous
      parasites suitable for biochemical assays, northern blots, flow cytometry,
      microarrays and proteomic analysis.

PMID- 17521752
TI  - Plakophilin-2 missense mutations in arrhythmogenic right ventricular
      cardiomyopathy.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is
      an inherited cardiac disorder characterized by life-threatening ventricular
      arrhythmias and fibrofatty replacement of myocardial tissue. Recent data suggest
      a dominant mode of inheritance in ARVD due to mutations in desmosomal proteins,
      plakophilin-2 (PKP2) in particular. We carried out a search for PKP2 mutations in
      the Finnish population representing a genetic isolate. METHODS: Mutations were
      detected by direct sequencing of PKP2 exons in 29 unrelated ARVD patients.
      Subcellular changes in ARVD associated with PKP2 mutations were searched for
      using immunohistochemistry and electron microscopy. RESULTS: We identified three
      PKP2 amino acid substitutions, absent in controls, in three (10%) cases. Two of
      them (Q62K and N613K) co-occurred in a patient with arrhythmia and structural
      changes of the heart. Visualized with plakophilin-2 antibodies, the intercalated
      disks in this compound heterozygous ARVD sample appeared wavier than in non-ARVD
      controls. Partial irregularities were occasionally seen in the organization and
      distribution of the cell-cell junctions. Relatives carrying one of these mutant
      alleles were phenotypically normal or showed only limited electrocardiographic
      (ECG) changes. The third substitution (Q59L) was detected in two ARVD probands
      with ventricular tachycardias, ECG abnormalities and right ventricular structural
      alterations. CONCLUSIONS: We identified two novel plakophilin-2 missense
      mutations associated with 10% of ARVD, and a previously reported Q62K variant
      with a possible disease modifying role. The low prevalence of predominantly
      missense mutations may present population-specific differences in the
      pathogenesis of ARVD. Our preliminary data also suggest that ultrastructural cell
      junction abnormalities may associate with plakophilin-2 mutations.

PMID- 17521753
TI  - Impact of significant chronic kidney disease on long-term clinical outcomes after
      drug-eluting stent versus bare metal stent implantation.
AB  - BACKGROUND: Higher rates of clinical and angiographic restenosis have been
      reported after coronary stenting in patients with significant chronic kidney
      disease (CKD). Whether drug-eluting stents (DES) can reduce long-term clinical
      events in CKD patients compared with bare metal stents (BMS) has not been
      established. METHODS: The study enrolled 104 consecutive significant CKD patients
      (estimated creatinine clearance <60 ml/min) treated with DES for 142 de novo
      coronary lesions, comprising 76 patients treated with sirolimus-eluting stents
      (SES) for 106 lesions and 28 patients treated with paclitaxel-eluting stents
      (PES) for 36 lesions. Data from these patients were compared to those from a
      control group comprising 50 patients treated with BMS during the preceding 1
      year. RESULTS: There were no differences in terms of baseline clinical
      characteristics except that the patients of the DES group were older, had a
      higher ratio of insulin treatment for diabetes mellitus, and had a more frequent
      history of previous percutaneous coronary intervention. The patients in the DES
      group had more unfavorable lesion characteristics with smaller reference vessel
      diameter (2.8 mm versus 3.3 mm; P<0.001) and longer lesion length (28.8 mm versus
      20.5 mm; P<0.001) than those in the BMS group. Compared to BMS, DES implantation
      had a lower 1-year major adverse cardiac events rate (cardiac death, non-fatal
      myocardial infarction or target vessel revascularization) (12% versus 26%;
      P=0.042). There were no significant differences between the SES and PES groups in
      terms of clinical outcomes. CONCLUSIONS: DES implantation for de novo coronary
      lesions in significant CKD patients reduces 1-year clinical events compared with
      BMS implantation.

PMID- 17521754
TI  - Determining the impact of food price and income changes on body weight.
AB  - We develop a theoretical model to identify conditions under which price and
      income changes are most likely to change weight. Although it is intuitive that
      raising the price of high-calorie food will decrease consumption of such goods;
      it is not clear that such an outcome will actually reduce weight. Our empirical
      analysis demonstrates a case where a tax on food away from home, a food intake
      category blamed for much of the rise in obesity, could lead to an increase in
      body weight; a finding which emphasizes the need to employ economic modeling when
      developing public policy to reduce obesity.

PMID- 17521755
TI  - Genotyping of Escherichia coli from environmental and animal samples.
AB  - The triplex PCR of Clermont et al. [Clermont, O., Bonacorsi, S., Bingen, E.,
      2000. Rapid and simple determination of the Escherichia coli phylogenetic groups.
      Appl. Environ. Microbiol. 66, 4555-4558.] was used to genotype E. coli isolates
      from the Mid-Atlantic region of the USA, obtained from freshwater, animal
      internal organs, and feces. Of 445 isolates subjected to genotyping, 118 isolates
      (26%) were genotype A, 111 (25%) genotype D, 140 (31%) genotype B1, and 76 (17%)
      genotype B2. All four genotypes were present in three sets of freshwater stream
      samples. When isolates from chicken cecal ingesta, cecal mucosa, and tracheal
      mucosa were screened, there was selective distribution of genotypes in these
      organs. Genotype D was rarely encountered in feces, milk, and intestinal tissues
      of dairy cows, while all four genotypes were represented in goose feces. Isolates
      from the feces of zoo animals reared in the US demonstrated a predominance of
      genotype B1. Thirty-six of the A isolates in our overall collection were
      subgenotype A(0), in which none of the three amplicons are observed; confirmation
      that these isolates were E. coli was done using an ancillary lacZ PCR assay. We
      conclude that the genotyping triplex PCR assay, used in combination with
      traditional culture methods, can be useful in categorizing E. coli from
      environmental and veterinary sources in the Mid-Atlantic region of the USA.

PMID- 17521756
TI  - Radiosensitization of tumour cell lines by the polyphenol Gossypol results from
      depressed double-strand break repair and not from enhanced apoptosis.
AB  - PURPOSE: New drugs are needed to increase the efficiency of radiotherapy in order
      to improve the therapeutic outcome of tumour patients. In this respect, the
      polyphenol Gossypol might be of interest, because of its effect on apoptosis and
      DNA repair, which is either mediated directly or indirectly via the inositol
      phosphate metabolism. It was investigated, whether these effects result in
      enhanced radiosensitivity of tumour cells. MATERIAL AND METHODS: Tumour cell
      lines investigated: A549, FaDu, H1299, MCF7 and Du145. Cell cycle distribution
      was determined by FACS analysis, apoptosis was measured by DAPI staining and
      caspase3/7 activity. Double-strand breaks (DSB) were investigated via gammaH2AX
      foci and cell survival by colony formation assay. The level of inositol
      phosphates was determined by HPLC, protein expression by Western blot. RESULTS:
      In A549 cells, Gossypol at concentrations 1microM strongly affects proliferation
      with only a modest arrest in the G1-phase, but with no increase in the fraction
      of apoptotic cells or the number of additional DSB. Additional DSB were only seen
      in FaDu cells, where Gossypol (2microM) was extremely toxic with a plating
      efficiency <0.002. When combined with irradiation, incubation with Gossypol (1
      2microM) was found to result in an enhanced radiosensitivity with, however, a
      substantial variation. While there was a strong radiosensitization for FaDu and
      Du145 cells, there was an intermediate response for A549 cells, but almost no
      effect for H1299 and MCF7 cells. This sensitization was not caused from an
      elevated rate of apoptosis, but primarily resulted from reduced DSB repair
      capacity. The reduction in DSB repair could be ascribed neither to changes in the
      level of repair proteins relevant for non-homologous end-joining (Ku70, Ku80, DNA
      PKcs) nor to changes in the level of higher phosphorylated inositols, whereby the
      latter were even found to be enhanced by Gossypol. CONCLUSIONS: For some tumour
      cell lines treatment with low concentrations of Gossypol can be used to inhibit
      DSB repair capacity and with that to increase the cellular radiosensitivity.

PMID- 17521757
TI  - Modulatory effect of NO on sodium currents in a neuroblastoma cell line: aspects
      of cell specificity.
AB  - Nitric oxide (NO) participates in the regulation of many cell functions in the
      CNS, including modulation of ion channel function by direct changes in the
      channel protein structure, modulating permeability or gating kinetics. The
      mechanisms by which NO donors modulate sodium currents are protein and tissue
      specific. The present paper concerns sodium currents in the neuroblastoma N1E-115
      cell line, applying whole-cell voltage clamp methods. Sodium currents were
      characterized in terms of the sensitivity to NO donors and the hydrophilic thiol
      oxidizer thimerosal. Parameters defining steady-state inactivation and
      activation, removal of inactivation and the voltage dependence of inactivation,
      were determined before and after thimerosal application. The results concerning
      the application of thimerosal showed blockade of the resting state,
      hyperpolarizing shifts of m(infinity) and h(infinity) curves, change in the
      voltage sensitivity and slower inactivating kinetics, tau(hf) and tau(hs) being
      affected in the same manner. The present results provide clear evidence for redox
      modulation of the sodium channel population in N1E-115 cells. Our results showed
      that the membrane-permeable alkylating agent (NEM) does not inhibit current
      reduction determined by thimerosal. We have reasons to suspect that the sodium
      channel population in N1E-115 cells differs in the proposed consensus sequence
      for nitrosylation or thimerosal cysteine oxidation.

PMID- 17521758
TI  - Modelling fungal growth using radial basis function neural networks: the case of
      the ascomycetous fungus Monascus ruber van Tieghem.
AB  - A radial basis function (RBF) neural network was developed and evaluated against
      a quadratic response surface model to predict the maximum specific growth rate of
      the ascomycetous fungus Monascus ruber in relation to temperature (20-40 degrees
      C), water activity (0.937-0.970) and pH (3.5-5.0), based on the data of Panagou
      et al. [Panagou, E.Z., Skandamis, P.N., Nychas, G.-J.E., 2003. Modelling the
      combined effect of temperature, pH and aw on the growth rate of M. ruber, a heat
      resistant fungus isolated from green table olives. J. Appl. Microbiol. 94, 146
      156]. Both RBF network and polynomial model were compared against the
      experimental data using five statistical indices namely, coefficient of
      determination (R(2)), root mean square error (RMSE), standard error of prediction
      (SEP), bias (B(f)) and accuracy (A(f)) factors. Graphical plots were also used
      for model comparison. For training data set the RBF network predictions
      outperformed the classical statistical model, whereas in the case of test data
      set the network gave reasonably good predictions, considering its performance for
      unseen data. Sensitivity analysis showed that from the three environmental
      factors the most influential on fungal growth was temperature, followed by water
      activity and pH to a lesser extend. Neural networks offer an alternative and
      powerful technique to model microbial kinetic parameters and could thus become an
      additional tool in predictive mycology.

PMID- 17521759
TI  - Predominant strains of thermophilic Campylobacter spp. in a German poultry
      slaughterhouse.
AB  - Campylobacter causes bacterial diarrhoea in man and is a common foodborne
      pathogen, that has been associated mainly with poultry carcasses and processed
      poultry products as well as with drinking water. Genotyping of Campylobacter spp.
      from poultry was done in order to prove if predominant stable strains in the food
      chain are present. The influence of the slaughter process on the stability should
      be determined. Thermophilic Campylobacter spp. from eight poultry flocks were
      isolated from cloacal swabs, carcasses and offal at different abattoir processing
      steps to determine their stability. DNA-fingerprinting was done using Pulsed
      Field Gel Electrophoresis (PFGE) with two enzymes (SmaI and KpnI) and ribotyping.
      More than 150 Campylobacter strains were ribotyped and these data were combined
      with the results of PFGE. Molecular typing showed that strains found in cloacal
      swabs before processing could also be isolated from carcasses and offal at
      different processing steps representing predominating stable strains. Strains
      with varying molecular pattern could additionally be detected at different
      processing steps. Both genotyping methods identified in agreement flock-specific
      strains. These remained stable through the slaughter of poultry and were not
      altered through the slaughter process. Despite the known genetic variability of
      thermophilic Campylobacter, stable predominant strains could be identified in the
      poultry slaughter process and those strains can thus enter the food chain.

PMID- 17521760
TI  - Vibrio parahaemolyticus strains isolated during investigation of the summer 2006
      seafood related diarrhea outbreaks in two regions of Chile.
AB  - Nine hundred cases of seafood related diarrhea were reported in the region of
      Puerto Montt, Chile during the austral summer of 2006. This is the continuation
      of the large outbreaks associated with the consumption of seafood containing the
      Vibrio parahaemolyticus serovar O3:K6 pandemic clonal group that arose last
      decade in Chile. The initial outbreaks occurred during the summer of 1998 in
      Antofagasta (23 degrees 39'S 70 degrees 24'W). Subsequently, outbreaks there were
      rare, but since 2004 outbreaks have been frequent farther south in Puerto Montt
      (41 degrees 29'S 72 degrees 24'W). The large outbreaks in Puerto Montt and their
      rarity in Antofagasta is atypical because the seawater temperature at Puerto
      Montt is 5 degrees C lower than at Antofagasta and the presence of V.
      parahaemolyticus in seafood has been associated with higher water temperatures.
      To better understand the role of seafood in outbreak occurrences in these
      regions, we analyzed the V. parahaemolyticus populations in clinical cases and
      shellfish from Puerto Montt during diarrhea outbreaks in 2006 and in shellfish
      from Antofagasta, where no cases were observed. Enrichment culture from shellfish
      yielded no V. parahaemolyticus from samples from the north, but its presence was
      detected in 80% of the samples from the south. Grouping of the V.
      parahaemolyticus isolates by the fragment restriction pattern of their DNA showed
      that all pathogenic (tdh+) isolates obtained from Puerto Montt shellfish
      corresponded to the serovar O3:K6 South East Asian pandemic clone, while the non
      pathogenic (tdh-) isolates corresponded to at least six discrete groups. The
      possible causes for the disappearance of the pandemic strain from the north and
      its persistence in the south are discussed.

PMID- 17521761
TI  - Diversity of Grapevine fanleaf virus isolates from Iran.
AB  - Enzyme-linked immunosorbent assay (ELISA) testing of 126 grapevine samples, from
      vineyards in the northwest region of Iran, detected Grapevine fanleaf virus
      (GFLV) in 33 samples. Total RNA from eight of the infected samples were subjected
      to reverse transcription polymerase chain reaction (RT-PCR) analysis using
      primers which corresponded to the virus coat protein and 3' non coding region of
      RNA 2. An expected 1620 bp DNA fragment was amplified from all the tested
      samples. PCR products from isolates B5, S1 and SH3 were cloned and the nucleotide
      sequences of three clones from each isolate were determined. The sequences showed
      that a DNA fragment of 1623 bp from isolate S1 and 1629bp from isolates B5 and
      SH3 were amplified. The fragments covered 1481 nucleotides of the 3' proximal
      region of the CP gene plus 142 or 148 nucleotides of the 3' non coding region.
      Alignment of the sequences revealed over 99% identities among clones from each
      isolate and 83-93% among clones from different isolates. Identities of 83-94%
      were found between the isolates from Iran and previously reported GFLV
      strains/isolates. Phylogenetic analysis based on CP sequences showed that
      isolates S1 and SH3 formed a distinct cluster but isolate B5 clustered with
      previously reported GFLV strains. This is the first report on sequence analysis
      of nearly full-length CP cDNA clones of GFLV isolates from Iran.

PMID- 17521762
TI  - A caspase-like gene from Heliothis virescens ascovirus (HvAV-3e) is not involved
      in apoptosis but is essential for virus replication.
AB  - Ascoviruses (AVs) are double-stranded DNA viruses causing a fatal disease in
      lepidopteran host larvae. A unique feature of AV infection is cleavage of host
      cells into membrane bound vesicles containing the virions. A recent study showed
      that a caspase from Spodoptera frugiperda AV (SfAV) is directly involved in
      initiation of apoptosis and eventually cell cleavage. Results shown here indicate
      that Heliothis virescens AV does not induce apoptosis in host cells. HvAV codes
      for a caspase-like protein but no apoptosis was observed when the gene was
      expressed in vitro. RNAi studies indicated that the gene is essential for virus
      replication.

PMID- 17521763
TI  - Completion of the mapping of transcription start sites for the five-gene block
      subgenomic RNAs of Beet yellows Closterovirus and identification of putative
      subgenomic promoters.
AB  - In the positive-sense RNA genome of Beet yellows Closterovirus (BYV), the 3'
      terminal open reading frames (ORFs) 2-8 are expressed as a nested set of
      subgenomic (sg) RNAs. ORFs 2-6, coding for the structural and movement proteins,
      form a 'five-gene block' conserved in closteroviruses. We mapped the 5'-end of
      the ORF 4 sgRNA, which encodes the p64 protein, at adenosine-11169 in the BYV
      genome. This completes the mapping of the transcription start sites for the five
      gene block sgRNAs of BYV. Computer-assisted analysis of the sequences upstream of
      BYV ORFs 2, 3, 4, 5, and 6 revealed two conserved motifs, which might constitute
      the subgenomic promoter elements. These motifs are conserved in the equivalent
      positions upstream of three orthologous genes of Citrus tristeza Closterovirus
      and two orthologous genes of Beet yellow stunt Closterovirus.

PMID- 17521764
TI  - Identification of European bat lyssavirus isolates with short genomic insertions.
AB  - Molecular typing has consistently identified European bat lyssaviruses from
      Germany as EBLV type 1a (EBLV-1a). This report confirms the presence of the
      closely related EBLV-1b in southern Germany, a group previously reported from The
      Netherlands, France and Spain. Furthermore, two of three German EBLV-1b isolates
      contain a 6 base pair insertion within the 3' untranslated region (UTR) of the
      nucleoprotein gene. This feature was shared with a third EBLV-1b isolate from a
      region of France adjacent to the French-German border. Further investigation
      revealed a two base pair insertion in a single isolate of EBLV-2 at the same
      genomic location. Although the length of the nucleoprotein gene 3'UTRs do vary
      between lyssavirus genotypes, such insertions have not been recorded within
      genotypes and could be the result of duplications within the nucleoprotein mRNA
      transcript polyadenylation signal.

PMID- 17521765
TI  - Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1
      influenza viruses in mice.
AB  - Virulence factors of influenza A (H5N1) viruses collected in 1997 from mammalian
      hosts were examined using a BALB/c mouse model. Fifteen amino acid (aa) residues
      in four influenza virus genes which correlated with high- and low-pathogenic
      phenotypes in mice were identified by analyzing sequence alignments. In addition
      to these specific residues, the effects of aa residue 627 of the PB2 gene, and
      the hemagglutinin (HA) and neuraminidase (NA) genes were also investigated using
      a reverse genetics system established with representative viruses of low (A/Hong
      Kong/486/97) and high (A/Hong Kong/483/97) pathogenicity for mice. None of 15 aa
      residues alone had any effect on virulence. The HA and NA genes had a synergistic
      effect on virulence and the absence of a glycosylation site at aa154 in the HA
      gene also increased virulence of virus. Multiple genes are involved in virulence
      of Hong Kong H5N1 influenza A viruses for mice with the presence of lysine at
      aa627 in the PB2 gene exhibiting a significantly larger effect than the HA and NA
      genes.

PMID- 17521767
TI  - [Outcomes and quality of life of elderly patients older than 80 years three
      months after a stay in an intensive care unit].
AB  - OBJECTIVES: The aging of the population has seen an increase in the number of
      elderly patients admitted to reanimation units. We sought to know the outcomes
      and evolution of the quality of life of a population of elderly patients after
      their experience with this type of service. METHOD: We included all patients
      older than 80 years who had been in two intensive care units in the Loire region
      of France between October 2005 and May 2006. We studied their state of mind 3
      months after they exited the service. Then, for the survivors, we used the
      Activities of Daily Living (ADL) scale and the generic questionnaire of health,
      the SF-36, to evaluate the evolution of their degree of autonomy and quality of
      life related to health compared to that one month prior to entry in the
      reanimation unit. RESULTS: We included 70 patients (mean age 85.2+/-4.5 years).
      At 3 months after exiting reanimation, the survival rate was 57%, and 28
      survivors underwent rating scale testing. The physical score of the SF-36 and the
      ADL score were significantly decreased as compared with that one-month before
      admission, with no significant difference in mental score of the SF-36. Physical
      deterioration did not have a significant effect on the evolution of perceived
      health (dimension GH of the SF-36), life and relations with others (dimension SF)
      or mental health (dimension MH). The decreased ADL score was correlated with that
      of the two physical dimensions of the SF-36, with no correlation with the four
      psychic dimensions. A total of 92% of patients were satisfied with their care in
      reanimation and three of four would agree to go back if their state required it.
      For the others, it is a question of respecting the will of the elderly patients
      confronted with reanimation care. CONCLUSION: Three months after intensive care
      with reanimation, elderly patients do not have significantly modified perceived
      health and psychic state as compared with objective deteriorated physical
      capacity. The absence of consensus on the threshold of old age and the quality-of
      life instrument to use prevents a comparison of our results with those in the
      literature. However, others have shown and we agree that elderly people could
      benefit from reanimation therapy.

PMID- 17521770
TI  - Metabolic training: new paradigms of exercise training for metabolic diseases
      with exercise calorimetry targeting individuals.
AB  - For patients with metabolic diseases, as with other diseases, exercise training
      is a fully recognized therapy. Such training helps obese patients stabilize
      weight after slimming. For patients with type 2 diabetics, it is both a
      prevention and a glucose-lowering treatment and reduces health care costs. We
      propose a targeted training for individuals at the level of maximal lipid
      oxidation (LIPOXmax) with a protocol of exercise calorimetry (four 6-min
      workloads) based on Brooks and Mercier's crossover concept. Calorimetric
      interpretation of gas exchange at the fifth and sixth minutes of each stage shows
      a bell-shaped curve for lipid oxidation that peaks at LIPOXmax, a point that
      varies considerably among individuals. As well, glucose oxidation is a linear
      function of power (carbohydrate cost of the watt). Such a calculation predicts
      fairly actual lipid oxidation over 45 min at the same level. Other protocols,
      with 3-min workloads used in sports medicine, are not reliable for patients with
      metabolic diseases. For obese adults and teenagers, as well as those with type 2
      diabetes, 2 months' training at the LIPOXmax (three sessions at 45 min per week)
      results in a net loss of fat mass, with preserved fat-free mass, and increased
      ability to oxidize lipids. At the end of this period, training can be "re
      targeted" to be more effective and, possibly, associated with other strategies
      with stronger exercise intensities. Therefore, metabolic training is a viable
      option for patients with metabolic diseases, but the full concept is still
      evolving. However, the major challenge remains to transform inactive individuals
      into active ones.

PMID- 17521771
TI  - Beer ethanol consumption and plasma homocysteine among patients with type 2
      diabetes.
AB  - We analyzed the association between beer and other type of ethanol consumption
      and tHcy levels among type 2 diabetic patients. Male type 2 diabetic patients
      without overt nephropathy were studied (n=242). Ethanol consumptions of the
      patients were 35.1+/-37.8mL/day for total ethanol, 13.9+/-15.2mL/day for beer
      ethanol and 21.2+/-32.1mL/day for non-beer ethanol. Both, total and non-beer
      ethanol consumption correlated with tHcy, whereas beer ethanol consumption showed
      a trend to inverse association with tHcy (standard regression coefficient, 0.184,
      0.283 and -0.110, respectively). Each intake of 30mL/day ethanol consumption was
      associated with an increase of tHcy of 0.6micromol/L for total ethanol and
      1.1micromol/L for non-beer ethanol and a decrease of tHcy of 0.7micromol/L for
      beer ethanol. Similar trend was observed in the analysis model which included
      only drinkers, and also in an adjusted analysis model. Plasma tHcy of beer only
      drinkers was lower than that of non-beer alcohol only drinkers (8.9+/
      1.9micromol/L versus 11.5+/-5.5micromol/L, P=0.003). Non-beer ethanol consumption
      might be less healthy compared with beer ethanol consumption among type 2
      diabetic patients in terms of the effects on tHcy.

PMID- 17521772
TI  - Matrices and scaffolds for drug delivery in tissue engineering.

PMID- 17521773
TI  - Effects of PACAP and VIP on cyclic AMP formation in rat neuronal and astrocyte
      cultures under normoxic and hypoxic condition.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal peptide (VIP) concentration (0.001-1000 nM)-dependently stimulated
      cyclic AMP production in rat primary neuronal and glial cell (astrocyte)
      cultures. The actions of both peptides were much more pronounced in astrocytes
      than in neuronal cultures. Stimulatory effects of PACAP and VIP on cyclic AMP
      formation were significantly smaller in cell cultures subjected to 24h lasting
      hypoxic conditions, induced either chemically (100 microM cobalt chloride) or by
      low 3% oxygen hypoxia, compared to the normoxic condition (95% air and 5% CO(2)).
      This picture contrasted with the effects of forskolin that were similar under
      normoxic and hypoxic conditions. It is suggested that hypoxia leads to changes in
      PACAP- and VIP-driven cyclic AMP-dependent signaling in the rat brain by
      influencing molecular processes likely occurring at the level of receptor protein
      or receptor-Gs protein coupling.

PMID- 17521774
TI  - Sequence characterization and expression patterns of two defensin-like
      antimicrobial peptides from the tick Haemaphysalis longicornis.
AB  - Two cDNAs encoding defensin-like antimicrobial peptides were cloned and sequenced
      from the tick Haemaphysalis longicornis. The full-length cDNA of Hlgut-defensin
      (H. longicornis midgut defensin) is 333bp, encoding an expected protein with 73
      amino acids. The full-length cDNA of Hlsal-defensin (H. longicornis salivary
      gland defensin) is 382bp, encoding an expected protein with 81 amino acids. The
      antibacterial activities of the synthetic peptides based on the Hlgut-defensin
      and Hlsal-defensin sequences were tested against a variety of Gram-positive and
      Gram-negative bacteria. Using real-time PCR, the tissue-specific expression of
      two defensin-like peptides were determined and it was also found that the gene
      transcripts of Hlgut-defensin and Hlsal-defensin were significantly induced by a
      lipopolysaccharide (LPS) injection.

PMID- 17521775
TI  - Tuning immune tolerance with vasoactive intestinal peptide: a new therapeutic
      approach for immune disorders.
AB  - The induction of immune tolerance is essential for the maintenance of immune
      homeostasis and to limit the occurrence of exacerbated inflammatory and
      autoimmune conditions. Multiple mechanisms act together to ensure self-tolerance,
      including central clonal deletion, cytokine deviation and induction of regulatory
      T cells. Identifying the factors that regulate these processes is crucial for the
      development of new therapies of autoimmune diseases and transplantation. The
      vasoactive intestinal peptide (VIP) is a well-characterized endogenous anti
      inflammatory neuropeptide with therapeutic potential for a variety of immune
      disorders. Here, we examine the latest research findings, which indicate that VIP
      participates in maintaining immune tolerance in two distinct ways: by regulating
      the balance between pro-inflammatory and anti-inflammatory factors, and by
      inducing the emergence of regulatory T cells with suppressive activity against
      autoreactive T-cell effectors.

PMID- 17521776
TI  - Proteomic analysis of peripheral leukocytes in Alzheimer's disease patients
      treated with divalproex sodium.
AB  - The molecular profiling of peripheral tissues, including circulating leukocytes,
      may hold promise in the discovery of biomarkers for diagnosing and treating
      neurodegenerative diseases, including Alzheimer's disease (AD). As a proof-of
      concept, we performed a proteomics study on peripheral leukocytes from patients
      with AD both before and during treatment with divalproex sodium. Using two
      dimensional gel electrophoresis and MALDI-TOF mass spectrometry, we identified 10
      differentially expressed proteins: two up-regulated proteins, 14-3-3 protein
      epsilon and peroxiredoxin 2; and eight down-regulated proteins, actin-interacting
      protein, mitogen activated protein kinase 1, beta actin, annexin A1,
      glyceraldehyde 3-phosphate dehydrogenase, transforming protein RhoA, acidic
      leucine-rich nuclear phosphoprotein 32 family member B, and a currently
      unidentified protein. A subset was validated on both the transcript and protein
      levels in normal human peripheral blood mononuclear cell cultures treated with
      valproic acid. These proteins comprise a number of functional classes that may be
      important to the biology of AD and to the therapeutic action of valproate. These
      data also suggest the potential of using peripheral leukocytes to monitor
      pharmaceutical action for neurodegenerative diseases.

PMID- 17521777
TI  - Antimicrobial studies of 2,4-dichloro-5-fluorophenyl containing oxadiazoles.
AB  - A series of 2,4-dichloro-5-fluorophenyl containing 1,3,4-oxadiazoles (10 and 11)
      were synthesized by POCl3 cyclization of 2,4-dichloro-5-fluorobenzoyl hydrazide
      (4) and 2-(2,4-dichloro-5-fluorophenyl)cinchoninyl hydrazide (8) with
      aryloxyacetic acids (9). The structures of newly synthesized compounds were
      characterized by spectral and elemental analyses. All the compounds were screened
      for their antibacterial and antifungal activities. Compounds 10a, 10d and 11g
      showed very good antimicrobial activity. Compound 10d showed good bactericidal
      and fungicidal activities.

PMID- 17521778
TI  - GdCl(3) catalysed Grieco condensation: a facile approach for the synthesis of
      novel pyrimidine and annulated pyrimidine fused indazole derivatives in single
      pot under mild conditions and their anti-microbial activity.
AB  - Indazole regioisomers such as 3-amino-4-(trifluoromethyl)-6-phenyl-1H-indazole-7
      carbonitrile 1 and 3-amino-6-(trifluoromethyl)-4-phenyl-1H-indazole-7
      carbonitrile 2 were independently reacted with formaldehyde followed by
      unsymmetrical, symmetrical and cyclic electron rich olefins in presence of
      GdCl(3) as catalyst and obtained pyrimidine fused indazole derivatives 3 and 4,
      respectively. The reaction is found to be concerted and an exclusive product is
      formed. Representative examples of compounds 3 and 4 were screened against Gram
      positive, Gram-negative bacteria and fungal species such as yeast and filamentous
      fungi in vitro. Compound 3f showed significant activity against all species of
      Gram-positive and Gram-negative bacteria, whereas compounds 3h and 4a showed the
      least activity with reference to penicillin as well as streptomycin. Similarly
      compound 3c showed promising activity against yeast and filamentous fungi whereas
      compound 3f is inactive at the maximum concentration of 150 microg/mL.

PMID- 17521779
TI  - [Upper limb lymphedema revealing breast cancer].
AB  - INTRODUCTION: Upper limb lymphedema occurs in 15 to 20% of patients after breast
      cancer treatment. Upper limb lymphedema without any history of neoplasia is an
      unusual situation. In this situation, breast cancer should be suspected.
      EXEGESIS: We reported two women, 53 and 67 years old, who developed upper limb
      lymphedema, 18 and 8 months before the diagnosis of breast cancer. In the two
      cases, clinical examination (breast and axillary palpation) was normal. In one
      case, mammography led to the diagnosis and in the other breast MRI was required
      to confirm the cancer. DISCUSSION: Upper limb lymphedema may be the presenting
      clinical feature of breast cancer. Breast cancer should be actively sought
      despite normal clinical and radiological findings. Breast MRI is required in this
      situation.

PMID- 17521780
TI  - The Meningitis Vaccine Project.
AB  - Epidemic meningococcal meningitis is an important public health problem in sub
      Saharan Africa. Current control measures rely on reactive immunizations with
      polysaccharide (PS) vaccines that do not induce herd immunity and are of limited
      effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate
      vaccines are effective in infants and have consistently shown an important effect
      on decreasing carriage, two characteristics that facilitate disease control. In
      2001 the Meningitis Vaccine Project (MVP) was created as a partnership between
      PATH and the World Health Organization (WHO) with the goal of eliminating
      meningococcal epidemics in Africa through the development, licensure,
      introduction, and widespread use of conjugate meningococcal vaccines. Since group
      A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing
      epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose)
      meningococcal A (Men A) conjugate vaccine through an innovative international
      partnership that saw transfer of a conjugation and fermentation technology to a
      developing country vaccine manufacturer. A Phase 1 study of the vaccine in India
      has shown that the product is safe and immunogenic. Phase 2 studies have begun in
      Africa, and a large demonstration study of the conjugate vaccine is envisioned
      for 2008-2009. After extensive consultations with African public health officials
      a vaccine introduction plan has been developed that includes introduction of the
      Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI)
      schedules but also emphasizes mass vaccination of 1-29 years old to induce herd
      immunity, a strategy that has been shown to be highly effective when the
      meningococcal C (Men C) conjugate vaccine was introduced in several European
      countries. The MVP model is a clear example of the usefulness of a "push
      mechanism" to finance the development of a needed vaccine for the developing
      world.

PMID- 17521781
TI  - Single dose of SA 14-14-2 vaccine provides long-term protection against Japanese
      encephalitis: a case-control study in Nepalese children 5 years after
      immunization. drjbtandan@yahoo.com.
AB  - In July 1999, a single dose of live-attenuated SA 14-14-2 Japanese encephalitis
      (JE) vaccine was administered to children living in the Bardiya, Banke and
      Kailali districts of Nepal. In 2004, the original vaccinated population
      experienced a fifth seasonal exposure to JE. We performed a case-control study
      comparing the prevalence of the administration of vaccine in patients with JE
      hospitalized in the Bardiya and Bheri Zonal hospitals and in age-sex matched
      controls resident in the Bardiya district. Among the 219 village controls, 114
      had been vaccinated (52.1%) while only one of 20 JE cases had received live
      attenuated JE vaccine. Five years after administration of a single dose, SA 14-14
      2 provided a protective efficacy of 96.2% (CI 73.1-99.9%).

PMID- 17521782
TI  - An evaluation of the immunogenicity and safety of a new trivalent meningococcal
      polysaccharide vaccine.
AB  - The immunogenicity and safety of a meningococcal trivalent A/C/W135
      polysaccharide vaccine was compared with that of a tetravalent A/C/Y/W135
      polysaccharide vaccine in a randomised, double blind trial. The study included
      360 adults, who received either a trivalent or tetravalent polysaccharide
      meningococcal vaccine. Antibody responses were determined by serum bactericidal
      antibody (rSBA) assays prior to vaccination and on day 28 and month 11 after
      vaccination. The percentage of participants in the trivalent vaccine group who
      had rSBA titres >or=8 on day 28 post-vaccination against serogroups A, C and W135
      meningococci were 99, 98 and 91%, respectively. The corresponding figures in the
      tetravalent vaccine group were 99, 99 and 90%. The percentage of participants
      with various cut off levels of rSBA against serogroups A, W135 and C meningococci
      on day 28 and 11-month post-vaccination and the incidence of adverse events did
      not differ significantly between the two groups.

PMID- 17521783
TI  - The first large epidemic of meningococcal disease caused by serogroup W135,
      Burkina Faso, 2002.
AB  - In 2001 a significant proportion of cases of meningococcal meningitis toward the
      end of a serogroup A epidemic in Niger and Burkina Faso was found to be caused by
      serogroup W135 meningococci. The World Health Organization put in place in
      several African countries an extended surveillance scheme in preparation for a
      possible epidemic situation. In January 2002, the first large epidemic of
      meningococcal disease caused by serogroup W135 started in Burkina Faso, resulting
      in more than 12,000 cases and 1400 deaths. We report here the results of the
      laboratory-based surveillance and the characteristics of the epidemic clone.

PMID- 17521784
TI  - Case-fatality ratio of bacterial meningitis in the African meningitis belt: we
      can do better.
AB  - In the African meningitis belt, reported case-fatality ratio (CFR) for meningitis
      are usually calculated on the basis of presumed cases. We reviewed 3509 presumed
      cases of bacterial meningitis reported in Niger for which a cerebrospinal fluid
      (CSF) sample had been tested later at the reference laboratory. The main
      aetiologies were Neisseria meningitidis (1496 cases), Streptococcus pneumoniae
      (303 cases) and Haemophilus influenzae (105 cases). The CFR of meningococcal
      meningitis was lower for serogroup A (5.5%) than for serogroups X (12%) and W135
      (12.7%). With a CFR of 49.8%, pneumococcal meningitis, albeit representing only
      20.7% of confirmed cases, accounted for 50% of the deaths. The disease burden of
      pneumococcal meningitis must be better taken into consideration in the future. As
      most treatments are presumptive, there is a urgent need for an easy-to
      administer, cheap first-line treatment effective on N. meningitidis as well as on
      S. pneumoniae and H. influenzae that would replace the single-dose oily
      chloramphenicol treatment which is the most frequent treatment administered
      today, independent of microbial aetiology and season. The development of
      diagnostic tools really suitable for remote health facilities also is an urgent
      challenge.

PMID- 17521785
TI  - Molecular surveillance of meningococcal meningitis in Africa.
AB  - Analysis of meningococcal strains recovered from outbreaks and epidemics in the
      African meningitis belt, using molecular methods, has demonstrated for nearly 20
      years the dominance among serogroup A organisms of a single clone complex, the
      sequence type 5 (ST-5) complex. However, a shift was observed since the mid-1990s
      when ST-5 gradually was replaced by ST-7 in all countries of the region. Since
      2001, outbreaks caused by serogroup W135 strains belonging to the ST-11 complex
      became an additional problem. Monitoring of the clones responsible for
      meningococcal disease provides important insights on the biology and epidemiology
      of this most serious pathogen.

PMID- 17521786
TI  - A multi-directional in vitro investigation into friction, damage and wear of
      innovative chondroplasty materials against articular cartilage.
AB  - BACKGROUND: The wear of the biomaterial/cartilage interface is vital for the
      development of innovative chondroplasty therapies. The aim of this study was to
      investigate potential chondroplasty biomaterials when sliding against natural
      articular cartilage under uniaxial reciprocating and multi-directional
      rotation/reciprocating motions. METHOD: Three biphasic hydrogels were compared to
      articular cartilage (negative control) and stainless steel (positive control).
      Friction was measured by means of a simple geometry friction and wear simulator.
      All tests were completed in 25% bovine serum at 20 degrees C. Mechanical
      alterations to the surface structure were quantified using surface topography.
      FINDINGS: Articular cartilage produced a constant friction value of 0.05
      (confidence interval=0.015) with and without rotation. Stainless steel against
      articular cartilage produced an increase in friction over time resulting in a
      peak value of 0.7 (confidence interval=0.02) without rotation, increasing to 0.88
      (confidence interval=0.03) with rotation. All biphasic hydrogels produced peak
      friction values lower than the positive control and demonstrated no difference
      between uni- and multi-directional motion. Degradation of the opposing cartilage
      surface showed a significant difference between the positive and negative
      controls, with the greater cartilage damage when sliding against stainless steel
      under uni-directional motion. INTERPRETATION: The lower friction and reduction of
      opposing cartilage surface degradation with the potential chondroplasty
      biomaterials can be attributed to their biphasic properties. This study
      illustrated the importance of biphasic properties within the tribology of
      cartilage substitution materials and future work will focus on the optimisation
      of biphasic properties such that materials more closely mimic natural cartilage.

PMID- 17521787
TI  - Spatial distribution and internal metal concentrations of terrestrial arthropods
      in a moderately contaminated lowland floodplain along the Rhine River.
AB  - Soil metal concentrations, inundation characteristics and abundances of 14
      arthropod taxa were investigated in a moderately contaminated lowland floodplain
      along the Rhine River and compared to the hinterland. Internal metal
      concentrations were determined for the orders of Coleoptera (beetles) and
      Araneida (spiders) and were related to soil concentrations. The floodplain was
      characterized by larger arthropod abundance than the hinterland, in spite of
      recurrent inundations and higher soil metal concentrations. Most arthropod taxa
      showed increasing abundance with decreasing distance to the river channel and
      increasing average inundation duration. For Cd, Cu, Pb and Zn, significant
      relations were found between arthropod concentrations and concentrations in soil.
      Significant relations were few but positive, indicating that increasing soil
      concentrations result in increasing body burdens in arthropods. For arthropod
      eating vertebrates, these results might imply that larger prey availability in
      the floodplain coincides with higher metal concentrations in prey, possibly
      leading to increased exposure to metal contamination.

PMID- 17521789
TI  - Organic pollutants in paper-recycling process water discharge areas: first
      detection and emission in aquatic environment.
AB  - In this study, eight compounds have been identified and quantified from the
      samples collected from paper-recycling process water discharge areas. In
      particular, five aryl hydrocarbons, including a novel chlorinated aryl ether,
      were identified for the first time as environmental pollutants. In the effluent
      stream, concentration levels of up to 1600 microg L(-1) and 190 microg g(-1) were
      detected in the surface water and surface sediment, respectively. The results of
      this study have raised concerns regarding the organic chemicals used in thermal
      paper and the environmental consequences of their release.

PMID- 17521790
TI  - Re-thinking the relationship between long-term condition self-management
      education and the utilisation of health services.
AB  - Encouraging self-management has been viewed as one means of reducing health
      service utilisation and contributing to improved demand management. However, the
      processes and imputed relationship between self-management education skills and
      health service contact are poorly understood. This paper reports on data from an
      embedded qualitative study which ran alongside a randomised controlled trial in
      England designed to test the clinical and cost effectiveness of a self-care
      support policy which found no statistically significant reductions in health
      service utilisation. Drawing on concepts from the sociology of chronic illness,
      analyses suggest that the biographical and social context relevant to
      individuals' experience of living with a long-term condition, history of health
      service utilisation, and relationships with health professionals are relevant to
      understanding the impact of self-management education and related policies aimed
      at bringing about changes in service use. Our study suggests that future health
      policy assumptions about utilisation in the context of chronic disease management
      and self-care support polices may benefit by acknowledging the complex,
      contextual and recursive nature of health service utilisation operating in the
      life worlds of patients' experience of living with a long-term condition.

PMID- 17521791
TI  - How healers manage the pluralistic healing context: the perspective of
      indigenous, religious and allopathic healers in relation to psychosis in Uganda.
AB  - This paper examines the relationships between service providers involved in
      caring for people with 'psychosis' in Uganda. Data from qualitative research
      investigating conceptualisations of 'madness' held by indigenous, religious and
      allopathic healers in urban Uganda are used to explore the attitudes of these
      different service providers towards each other. Case-vignettes of individuals
      with a diagnosis of a psychotic disorder were discussed by the healers and real
      cases were discussed by allopathic doctors, and their discourse was analysed. The
      healers varied in their attitudes towards other parts of the healing context. The
      indigenous and religious healers were tolerant of allopathic medicine, although
      the religious healers were inclined to explain its success in terms of a
      Christian or Islamic framework. In contrast, the allopathic healers made little
      reference to religious healers and were ambivalent towards indigenous healers.
      Finally, the relationship between the religious and indigenous healers emerged as
      one of conflict. The religious healers negated the beliefs and methods of the
      indigenous healers, whilst the indigenous healers regarded indigenous
      spirituality and evangelical Christianity as incompatible. Historical and social
      psychological perspectives are used to understand these differences. There appear
      to be opportunities for greater dialogue between indigenous and religious healers
      and allopathic doctors and this could contribute to a more integrative model of
      care for individuals with psychotic experiences in Uganda.

PMID- 17521792
TI  - Immunohistochemical and immunoblot analysis of Dopamine and cyclic AMP-regulated
      phosphoprotein, relative molecular mass 32,000 (DARPP-32) in the prefrontal
      cortex of subjects with schizophrenia and bipolar disorder.
AB  - Dopamine and cyclic adenosine 3':5'-monophosphate (AMP)-regulated phosphoprotein,
      relative molecular mass 32,000 (DARPP-32), plays an important role in modulating
      the functions of various neurotransmitter systems. To explore the alterations in
      DARPP-32 in subjects with schizophrenia and bipolar disorder, we employed
      immunohistochemical and Western blotting techniques and examined the distribution
      and expression of DARPP-32 in the postmortem dorsolateral prefrontal cortex
      (DLPFC) from 12 subjects with schizophrenia, 10 subjects with bipolar disorder,
      and 11 control subjects. Immunohistochemical study demonstrated that DARPP-32
      immunolabeling in the neuronal soma from subjects with schizophrenia and bipolar
      disorder was lower than in that from the controls. The results of the immunoblot
      analysis were consistent with those of the immunohistochemistry, and the amount
      of DARPP-32 in subjects with schizophrenia and bipolar disorder was found to be
      lower than that in the control subjects. The present study suggests that DARPP-32
      decreases in the DLPFC of patients with schizophrenia and bipolar disorder, and
      further suggests that this decrease is associated with dysfunction of
      dopaminoceptive neurons in the DLPFC of patients affected by these two mental
      disorders.

PMID- 17521793
TI  - Anxiolytic-like effects of oleamide in group-housed and socially isolated mice.
AB  - Oleamide (cis-9,10-octadecenoamide) is an endogenous sleep-inducing lipid and
      prototypic member of a new class of biological signaling molecules identified in
      recent years. In the present study, the anxiolytic-like effect of oleamide was
      studied in several experimental models of anxiety in group-housed and socially
      isolated mice. As the results show, socially isolated mice exhibited an
      anxiogenic-like profile in the elevated plus-maze test, the light/dark test, and
      the hole-board test, which could be significantly reversed by oleamide (10 or 20
      mg/kg, i.p.). Moreover, oleamide significantly reduced the anxiety levels in
      grouped-housed mice. In the isolation-induced aggressive test, oleamide markedly
      reduced the attacking duration and increased the attacking latency. It is
      concluded that oleamide has an anxiolytic-like effect in socially isolated or
      group-housed mice, which suggests that fatty acid amides might be involved in the
      regulation of anxiety-related behavior in mice.

PMID- 17521794
TI  - "Inverted Takotsubo" pattern.

PMID- 17521795
TI  - Strict glucose control: where are we now?

PMID- 17521796
TI  - Sternum fracture and haemorrhage after cardiopulmonary resuscitation.

PMID- 17521797
TI  - Effectiveness and long-term outcome of cardiopulmonary resuscitation in pediatric
      intensive care units in Spain.

PMID- 17521798
TI  - Ajmaline challenge in Brugada syndrome.

PMID- 17521799
TI  - The associative processes involved in faces-proper names versus animals-common
      names binding: a comparative ERP study.
AB  - Recognizing people involves creating and retrieving links between distinct
      representations such as faces and names. In previous research we have shown that
      the retrieval of face/name associations produced cerebral activities lateralized
      in the left hemisphere and spreading from posterior to anterior sites after about
      300ms. The present ERP study was performed to compare the specific
      electrophysiological activities elicited by the retrieval of face/proper name
      (FP) and animal/common name (AC) associations. Using a subtraction method to
      isolate the specific binding activities, we showed that both kinds of association
      produced two main posterior negative/anterior positive complexes, with a more
      frontal distribution for AC, and bilateral temporal activities. These findings
      confirm that general associative processes - independent of the kind of
      association - are not simply the sum of the activities elicited by each stimulus,
      and that they could involve both unimodal sensory and multimodal convergence
      regions of the brain.

PMID- 17521800
TI  - Successful treatment of FIGO stage IV gestational choriocarcinoma occurring 2
      months after delivery.

PMID- 17521801
TI  - Attenuation and size distribution measurements of Definity and manipulated
      Definity populations.
AB  - The contrast agent Definity has recently been shown to have substantial nonlinear
      activity at high ultrasound frequencies (>10 MHz). In this study, measurements
      were performed to characterize the frequency dependent attenuation properties of
      Definity and populations of Definity that had been modified to preferentially
      isolate smaller bubbles through decantation or mechanical filtration. A
      narrowband pulse-echo substitution method was employed with a series of four
      transducers covering the frequency range from 2 to 50 MHz. "Native" Definity has
      peak in attenuation in the vicinity of 10 MHz and remains high until 50 MHz. This
      pattern is significantly different from other clinically approved agents and is
      consistent with recent reports of nonlinear activity at high frequencies. With
      increasing decantation times, the attenuation peak becomes more diffuse and
      occurs at progressively higher frequencies. By 3 h for example, attenuation
      continues to rise until 30 MHz. The bubble size distribution undergoes
      preferential skewing toward smaller bubbles with increasing decantation time.
      Between 30 s and 3 h, the mean bubble diameter goes from 3.99 to 0.98
      micrometers. Mechanical filtration with 2 and 1 microm pores causes attenuation
      to rise until 15 and 40 MHz, respectively. Definity can therefore be manipulated
      to improve its relative activity at higher frequencies (>10 MHz), which has
      implications for ultrasound biomicroscopy and intravascular ultrasound
      applications. Further, these results suggest that agent handling can have a
      substantial impact on size distributions affecting lower frequency applications.
      Shell friction estimates derived from these data are lower than those reported
      for larger bubbles at lower frequencies.

PMID- 17521802
TI  - Statistical segmentation of surgical instruments in 3-D ultrasound images.
AB  - The recent development of real-time 3-D ultrasound (US) enables intracardiac
      beating-heart procedures, but the distorted appearance of surgical instruments is
      a major challenge to surgeons. In addition, tissue and instruments have similar
      gray levels in US images and the interface between instruments and tissue is
      poorly defined. We present an algorithm that automatically estimates instrument
      location in intracardiac procedures. Expert-segmented images are used to
      initialize the statistical distributions of blood, tissue and instruments. Voxels
      are labeled through an iterative expectation-maximization algorithm using
      information from the neighboring voxels through a smoothing kernel. Once the
      three classes of voxels are separated, additional neighboring information is
      combined with the known shape characteristics of instruments to correct for
      misclassifications. We analyze the major axis of segmented data through their
      principal components and refine the results by a watershed transform, which
      corrects the results at the contact between instrument and tissue. We present
      results on 3-D in-vitro data from a tank trial and 3-D in-vivo data from cardiac
      interventions on porcine beating hearts, using instruments of four types of
      materials. The comparison of algorithm results to expert-annotated images shows
      the correct segmentation and position of the instrument shaft.

PMID- 17521803
TI  - Emission of Pb and PAHs from thermally co-treated MSWI fly ash and bottom ash
      process.
AB  - Municipal solid waste incinerator (MSWI) fly ash was regarded as a hazardous
      material because concentrations of TCLP leaching solution exceeded regulations.
      Previous studies have investigated the characteristics of thermally treated slag.
      However, the emissions of pollutant during the thermal treatment of MSWI fly ash
      have seldom been addressed. The main objective of this study was to evaluate the
      emission of Pb and PAHs from thermally co-treated MSWI fly and bottom ash
      process. The experimental parameters included the form of pretreatment, the
      proportion of bottom ash (bottom ash/fly ash, B/F=0, 0.1 and 1) and the retention
      time. The toxicity of thermally treated slag was also analyzed. The results
      indicated that (1) Pb emission occurred only in the solid phase and that PAHs
      were emitted from both solid and gas phases during thermal treatment process. (2)
      Washing pretreatment reduced not only the TCLP leaching concentration of Pb (from
      15.75 to 1.67 mg/L), but also the emission of PAHs from the solid phase during
      thermal treatment process. (3) Adding bottom ash reduced the TCLP leaching
      concentration of thermally treated slag. (4) The concentration of Pb emission
      increased with retention time. (5) The thermal treatment reduced the toxicity of
      raw fly ash effectively, the inhibition ratio of raw fly ash and thermal treated
      slag were 98.71 and 18.35%, respectively.

PMID- 17521804
TI  - Photocatalytic activity of TiO2 doped with boron and vanadium.
AB  - Boron (B)- and vanadium (V)-doped TiO(2) photocatalysts were synthesized using
      modified sol-gel reaction processes and characterized by X-ray diffraction (XRD),
      Raman spectroscopy and N(2) physisorption (BET). The photocatalytic activities
      were evaluated by monitoring the degradation of methylene blue (MB). The results
      showed that the materials possess high surface area. The addition of B favored
      the transformation of anatase to rutile, while in the presence of V, anatase was
      the only phase detected. The MB degradation on V-doped TiO(2) was significantly
      affected by the preparation method. In fact while the presence of V in the bulk
      did not influence strongly the photoreactivity under visible irradiation, an
      increase of surface V doping lead to improved photodegradation of MB. The
      degradation of MB dye indicated that the photocatalytic activities of TiO(2)
      increased as the boron doping increased, with high conversion efficiency for
      9mol% B doping.

PMID- 17521805
TI  - Sonochemical disinfection of municipal wastewater.
AB  - The application of high intensity, low frequency ultrasound for the disinfection
      of simulated and septic tank wastewaters is evaluated in this work. Laboratory
      scale experiments were conducted at 24 and 80kHz ultrasound frequency with horn
      type sonicators capable of operating in continuous and pulsed irradiation modes
      at nominal ultrasound intensities up to 450W. For the experiments with simulated
      wastewaters, Escherichia coli were used as biological indicator of disinfection
      efficiency, while for the experiments with septic tank wastewaters, the total
      microbiological load was used. Complete elimination of E. coli could be achieved
      within 20-30min of irradiation at 24kHz and 450W with the efficiency decreasing
      with decreasing intensity and frequency. Moreover, continuous irradiation was
      more effective than intermittent treatment based on a common energy input.
      Irradiation of the septic tank effluent prior to biological treatment at 24kHz
      and 450W for 30min resulted in a three-log total microbiological load reduction,
      and this was nearly equal to the reduction that could be achieved during
      biological treatment. Bacterial cell elimination upon irradiation was
      irreversible as no reappearance of the microorganisms occurred after 24h.

PMID- 17521806
TI  - Studies on electrochemical treatment of wastewater contaminated with organotin
      compounds.
AB  - Different anode materials were tested to evaluate their suitability to eliminate
      organotin compounds electrochemically from shipyard process waters. The capacity
      of two types of anode materials was investigated: niobium coated with boron-doped
      diamond (BDD) and titanium coated with iridium dioxide, (Ti/IrO(2)). The aim of
      this work was to characterize the performance of the process using both anode
      materials at different current densities, and also to evaluate the generation of
      by-products. A further objective of this work was to evaluate if operating at low
      potentials with BDD anodes (to avoid the generation of elemental oxygen) the
      consumption of energy for degradation of pollutants could be minimized. The
      processes were tested on synthetic and real shipyard water containing
      approximately 25,000ngL(-1) of tributyltin (TBT) (as Sn) and 5,000ngL(-1)
      dibutyltin. The range of current densities was between 6 and 70mAcm(-2). The
      results showed that electrochemical treatment is suitable to eliminate organotins
      down to very low concentrations following a stepwise debutylation mechanism. Both
      anode materials exhibited a similar performance with energy consumption in the
      range of 7-10kWhm(-3) in order to decrease organotins down to 100ngL(-1) (as Sn).
      For the water composition tested, BDD did not outperform Ti/IrO(2) as initially
      expected, most probably because organotins were not only oxidized by OH, but also
      by active chlorine compounds generated by the oxidation of chloride present in
      the wastewater (1.6gL(-1), Cl(-)) with both anode materials. It was also found
      that the residual oxidants remaining in the treated effluent had to be eliminated
      if the water is to be discharged safely in the aquatic environment.

PMID- 17521807
TI  - Photolysis of 2,4-dinitrotoluene in various water solutions: effect of dissolved
      species.
AB  - This work investigates the photolysis of 2,4-dinitrotoluene (2,4-DNT) in the
      presence of different dissolved species. Initial experiments revealed that the
      direct photolysis of 2,4-DNT in deionized water solutions under sunlight and
      artificial light followed a pseudo-first order kinetic. Humic acids (HA) appeared
      to act as sensitizers in the aqueous photolysis of 2,4-DNT and the calculated
      half life was found to be approximately 2h, which is faster than the half life
      calculated in the case of deionized water ( approximately 4h). The presence of
      salt (NaCl) in the deionized water solutions was found to have a more pronounced
      sensitizing effect upon the photolysis of 2,4-DNT, yielding half lives of the
      order of 1h. Investigations on seawater and groundwater spiked with 2,4-DNT,
      revealed that photolysis is enhanced in the order seawater > groundwater
      approximately deionized water.

PMID- 17521808
TI  - Changes in self-perceived role identity modulate pain perception.
AB  - Pain is an experience including physiological and psychological factors. We
      assume that emotions may be elicited and increased through self-perceived role
      identity and that change of role identity alters quality and intensity of pain
      perception. We used role-play strategies to assess whether pain can be better
      tolerated whenever, in an unavoidable and unpleasant context, role identity
      confers pain a meaningful and thus suitable character. We induced antithetic
      roles in 21 actors who received heat stimuli on their arms before and after role
      play conditions. Pain tolerance, skin conductance and voice signals were
      measured. Pain tolerance increased for heroes/heroines and decreased for faint
      hearts. Men showed higher pain tolerance. Heroes/heroines evaluated heat stimuli
      as more intense. Faint-hearts found pain stimuli more affectively loaded at lower
      temperatures. Women showed higher pain ratings. Hence, self-perception influences
      pain perception. Role-play strategies may be of value for new pain management
      strategies.

PMID- 17521809
TI  - Gut sensations in diabetic autonomic neuropathy.
AB  - The pathogenesis of gastrointestinal symptoms in diabetes mellitus is complex and
      multi-factorial. Diabetes induced peripheral and central changes in the neuronal
      pain matrix may be of importance and were explored using a new multi-modal and
      multi-segmental sensory testing approach. The sensitivity to mechanical, thermal
      and electrical stimulations in the oesophagus and duodenum was assessed in 12
      type-1 diabetic patients with proven autonomic neuropathy and severe
      gastrointestinal symptoms using a comprehensive stimulation device aiming to
      activate different gut nerves and pain mechanisms. Twelve healthy subjects served
      as controls. The sensory response and the somatic referred pain areas were
      recorded. In the diabetic patients an overall hyposensitivity to the combination
      of all stimulations was found in the oesophagus and duodenum (P=0.02). Post hoc
      analysis revealed hyposensitivity to mechanical stimulations in the oesophagus
      (P=0.006) and duodenum (P=0.002), and to thermal (P<0.001) and electrical
      (P=0.005) stimulations in the oesophagus and duodenum combined. The
      hyposensitivity in the gut was accompanied by a 46% increase in the somatic
      referred pain areas (P=0.04) indicating central neuronal changes. The multi-modal
      and multi-segmental sensory testing approach indicates that the sensory nerves
      are widely affected in the GI tract and generalized to nerves in all layers of
      the gut. Changes in the neuronal pain matrix including interactions between
      peripheral and central pain mechanisms may be involved in the pathogenesis of
      gastrointestinal symptoms in long-standing diabetes. Future targets in the
      treatment of gastrointestinal symptoms in diabetic patients with autonomic
      neuropathy could be based on modulation of the central nervous system
      excitability.

PMID- 17521810
TI  - A preliminary investigation of affective interaction in chronic pain couples.
AB  - The objective of this preliminary study was to examine the extent to which
      affective marital interaction related to depressive symptoms in persons with
      chronic pain and their spouses and to pain severity in persons with pain. Couples
      from the community completed self-report surveys and engaged in a videotaped
      conversation on a topic of mutual disagreement that was coded for three affect
      types (i.e., anger/contempt, sadness, humor). Humor was positively related to
      marital satisfaction in both partners. Spouse anger/contempt and sadness were
      positively related to depressive symptoms in spouses. Several significant
      interaction effects between couple pain status (i.e., whether one or both
      partners reported pain) and affect also emerged. Specifically, sadness in the
      participant designated as the person with pain was associated with greater
      depressive symptoms and pain severity when only he or she reported pain whereas
      sadness was related to fewer depressive symptoms and less pain severity when both
      partners reported pain. The relationships between spouse anger and spouse
      depressive symptoms and between spouse humor and pain severity in the person with
      pain were also moderated by couple pain status. These exploratory findings can be
      interpreted in light of emotion regulation and pain empathy theories. For
      example, partners who have not experienced pain themselves may fail to empathize
      with persons in pain, thus preventing effective emotion regulation. When both
      spouses report chronic pain, expressions of negative affect may instead promote
      emotion regulation because the affect is experienced with a spouse who may be
      more empathetic.

PMID- 17521811
TI  - Understanding the role and significance of gender differences in pain and
      depression in Chinese elders with osteoarthritis.

PMID- 17521812
TI  - Igniting the spark?

PMID- 17521813
TI  - Involvement of ATP and its receptors on nociception in rat model of masseter
      muscle pain.
AB  - The exact mechanism of the masseter muscle pain recognized as a prominent symptom
      in temporomandibular disorders remains unclear, although it is clinically known
      that excessive muscular contraction causes tenderness in masseter muscles. It has
      been demonstrated that P2X3 receptors (P2X3Rs) in sensory neurons play a role in
      pain signaling from the periphery. We determined the role of P2X(3)R on pressure
      pain and mechanical hyperalgesia in a newly developed rat model of masseter
      muscle pain. The pain in the masseter muscle was assessed by the pressure pain
      threshold (PPT), which was defined as the amount of pressure required to induce
      head flinching. In naive animals, systemic treatment with morphine was associated
      with increase of PPTs. Changes in PPTs were examined after administration of P2XR
      agonists or antagonists into the masseter muscle. The masseter muscle injection
      of alpha,beta-meATP (P2X(1,3,2/3)R-specific agonist) induced a significantly
      greater behavioral response than its vehicle. This enhanced response was
      completely blocked by the co-application of alpha,beta-meATP with PPADS
      (P2X(1,2,3,5,1/5,2/3)R-specific antagonist). Excessive contraction in masseter
      muscle was produced by electrical stimulation. The exerted masseter muscles
      showed a significant reduction in PPTs indicating the induction of mechanical
      hyperalgesia of the muscle. Moreover, administration of PPADS to the exerted
      masseter muscles produced a complete recovery of reducing PPT.
      Immunohistochemically, the number of P2X3R-positive neurons innervating the
      masseter muscles increased in the excessively contracted condition in trigeminal
      ganglia. Our results suggested that P2X3R plays an important role in pressure
      pain and mechanical hyperalgesia in masseter muscle caused by excessive muscular
      contraction.

PMID- 17521814
TI  - Can fleas from dogs infected with canine visceral leishmaniasis transfer the
      infection to other mammals?
AB  - In order to investigate the possible role of dog fleas in the transmission of
      trypanosomatids, ectoparasites were removed from 59 dogs testing positive for
      canine zoonotic visceral leishmaniasis according to the indirect fluorescent
      antibody test (IFAT). Of the fleas collected, 4/207 (1.9%) showed the presence of
      promastigotes in smears stained by Giemsa, whilst 43/144 (29.9%) exhibited
      positive polymerase chain reaction (PCR) amplification assays for Leishmania DNA.
      Fleas (409) from 9 Leishmania chagasi-infected dogs, each hosting more than 20
      fleas per animal, were macerated and administered by peritoneal injection or
      orally to 36 hamsters. After 6 months, the 30 surviving hamsters were sacrificed
      and liver and spleen fragments were removed for PCA assay and to produce imprint
      smears, whilst blood samples were subjected to IFAT assay. Sixteen hamsters
      tested positive for Leishmania infection, 14 on the basis of PCR amplification
      and four by IFAT assay (two animals testing positive in both assays). Of the
      infected hamsters, 11/16 (68.7%) had been infected peritoneally and 5/16 (31.2%)
      orally. The imprint smears for all animals were, however, negative. Since both
      PCR and IFAT could present cross-reactivity for Leishmania and Leptomonas, the
      possibility of oral transmission of L. chagasi by fleas cannot be proven
      unambiguously even though the hamsters developed infection.

PMID- 17521815
TI  - Cooling of the burn wound: the ideal temperature of the coolant.
AB  - BACKGROUND: The beneficial effects of cooling a fresh burn wound were well
      demonstrated. However, there are still conflicting reports as to the optimum
      temperature of coolant, duration of application and effects in limiting tissue
      damage. A study was undertaken to investigate this, the importance of the
      temperature of, and the time period of application of the coolant. MATERIALS AND
      METHODS: Four identical deep dermal wounds were created on the back of 10
      anaesthetised pigs. Each animal served as an independent experimental model. The
      effectiveness of cooling was monitored by measuring intradermal temperatures. The
      animals were divided into two groups; using ice water and tap water as the
      coolants. In each pig one wound was not cooled (wound 1). Three were cooled; one
      immediately for 30 min in group 1 and for 4 h in group 2 (wound 2). The other two
      wounds were cooled after 30 min for 30 min and 3 h (wounds 3 and 4,
      respectively). RESULTS: It was found that the temperature of the coolant was
      crucial. When ice water of 1-8 degrees C (group 1) was used more necrosis than in
      the wounds that were not cooled was seen. When tap water was used at 12-18
      degrees C (group 2) it was demonstrated clinically and histologically that the
      cooled wounds had less necrosis than the uncooled wounds and thus healed faster.
      In group 2 the beneficial effects of cooling were still present when delayed for
      half an hour. CONCLUSION: First aid cooling of a burn wound with tap water is an
      effective method of minimising the damage sustained during a burn, and is
      universally and immediately available. Ice water cooling is associated with an
      increase in tissue damage.

PMID- 17521816
TI  - Supraclavicular bilobed fasciocutaneous flap for postburn cervical contractures.
AB  - Anterior cervical contractures after burn are a common problem in the treatment
      of sequelae in burnt patients. The contracture itself and the hypertrophic
      scarring can cause functional limitation and aesthetic disfigurement. As a
      consequence, the reconstruction of this area is a challenge to surgeons that must
      choose a procedure, which improves functionality and aesthetic appearance in
      addition to reversing the contracture, the surgical goal of avoiding a new scar
      band over time is added. We present three patients with moderate (grade II)
      cervical contractures caused by suicide attempt and reconstructed by means of a
      bilobed flap based on the supraclavicular axis with the purpose of avoiding
      grafts in the donor area and performing it in a single procedure. This flap is
      useful and reliable for reconstruction of defects caused by cervical scars in non
      collaborative and psychologically unstable patients. The anatomy, surgical
      procedure and results in our series are presented in this article.

PMID- 17521817
TI  - Aeromonas infection in critically ill burn patients.
AB  - Aeromonas infection in burn patients is extremely uncommon. Here we report on
      four cases of Aeromonas infection in burn patients admitted to the BICU at the
      Singapore General Hospital burn unit between June 2001 and May 2006. Two patients
      had positive blood cultures, and the other two had tissue samples with growth.
      There was no history of exposure to soil or fresh water in all patients. The
      average age of patients was 35 years (range 24-41) and the average % TBSA was 48%
      (range 35-80). Cultures were isolated between days 2 and 4 post burn. There was
      one mortality in the series. Increasing antibiotic resistance was noted among
      isolates of Aeromonas. Continued vigilance is essential to detect infection
      early, even in the absence of a suggestive history, with adequate debridement and
      appropriate antibiotic therapy.

PMID- 17521818
TI  - Silymarin, the antioxidant component of Silybum marianum, protects against burn
      induced oxidative skin injury.
AB  - BACKGROUND: Despite recent advances, severe burn is one of the most common
      problems faced in the emergency room. Major thermal injury induces the activation
      of an inflammatory cascade resulting in local tissue damage, to contribute to the
      development of subsequent damage of multiple organs distant from the original
      burn wound. OBJECTIVE: Silymarin, the major component of milk thistle has been
      shown to have antioxidant properties. In the present study, we investigated the
      putative antioxidant effect of local or systemic silymarin treatment on burn
      induced oxidative tissue injury. METHODS: Wistar albino rats were exposed to 90
      degrees C bath for 10 s to induce burn. Silymarin either locally (30 mg/kg)
      applied on 4 cm(2) area or locally+systemically (50 mg/kg, p.o.) was administered
      after the burn and repeated twice daily. Rats were decapitated 48 h after injury
      and blood was collected for tumor necrosis factor-alpha (TNF-alpha) and lactate
      dehydrogenase (LDH) activity. In skin tissue samples malondialdehyde (MDA) and
      glutathione (GSH) levels, myeloperoxidase (MPO) activity, and luminol-lucigenin
      chemiluminescense (CL) were measured in addition to the histological evaluation.
      RESULTS: Burn caused a significant increase in TNF-alpha and LDH levels. MDA
      levels were increased and GSH levels were decreased in the skin at 48 h after
      burn. Both local and systemic silymarin treatments significantly reversed these
      parameters. The raised MPO activity and luminol-lucigenin CL were also
      significantly decreased. CONCLUSION: Results indicate that both systemic and
      local administration of silymarin was effective against burn-induced oxidative
      damage and morphological alterations in rat skin. Therefore, silymarin merits
      consideration as a therapeutic agent in the treatment of burns.

PMID- 17521819
TI  - Reconstruction of the face and neck scar contractures using staged transfer of
      expanded "Super-thin flaps".
AB  - BACKGROUND: The authors introduced the "Super-thin flap" concept, which is
      sometimes called the subdermal vascular network (SVN) flap, in 1994. Since 1994,
      we have reconstructed face and neck scar contractures using various types of
      "Super-thin flaps." In this report, we introduce expanded "Super-thin flaps" for
      reconstruction of the face and neck for the first time in a patient. METHODS:
      Since 2000 we have used 21 expanded flaps to reconstruct 21 face or neck scar
      cases in nine males and 12 females. In the first operation, an expander was
      inserted on the fascia of the pectoralis major muscle, and then about 1,000 cc of
      saline was injected during a 2-month period. In the second operation, the flap
      was thinned primarily and applied to the recipient site. Three weeks after the
      second operation, the pedicle of the flap was cut down and sutured. RESULTS: Flap
      size ranged from 4 cm x 14 cm to 10 cm x 22 cm. Expanded volume ranged from 800
      cc to 1,200 cc. All flaps survived completely and scar tissues were replaced with
      normal skin. Flaps did not shrink after the operations, and contractures did not
      recur. CONCLUSION: Advantages of the expanded flaps are presented: (1) Large
      flaps can be harvested because of the expander; (2) Extremely thin flaps can be
      safely employed; (3) Texture and color match are good; (4) Donor site can be
      closed primarily; and (5) Microsurgery is not required. However, the disadvantage
      of the method is the requirement for two or three operations.

PMID- 17521820
TI  - Macroscopic and histological findings in the healing process of inhalation
      injury.
AB  - Although many investigators reported the diagnostic and therapeutic value of
      bronchoscopy in the early stage of inhalation injury, few findings in the late
      stage of inhalation injury have been reported. We investigated histopathological
      changes of in trachea and bronchi after inhalation injury. Five survivors with
      inhalation injury underwent bronchoscopic examinations combined with biopsies
      from the early stage to the late stage. Although the bronchotracheal membranes
      improved to near normal under the bronchoscopic findings in the late or recovery
      stage, invasion of inflammatory cells and the capillary dilatation in the
      subepithelial region were still remarkable histologically. Goblet cells also
      increased on the surface of mucous membranes. In cases of the inhalation injury
      with severe burn, pulmonary edema, bronchial edema and secretions tended to be
      prolonged. Results suggested that continuous secretions in the respiratory tracts
      sometimes cause airway obstruction. Bronchoscopic and histologic findings in the
      healing process of inhalation injury predict long-term pulmonary functional
      outcome. Moreover, the aggressive pulmonary toilet seemed to be effective in
      removing foreign particles and accumulated secretions which also cause the
      inflammatory response and the obstruction in inhalation injury.

PMID- 17521821
TI  - Pharmacological modulation of wound healing in experimental burns.
AB  - Factors involved in wound healing and their interdependence are not yet fully
      understood; nevertheless, new prospects for therapy to favor speedy and optimal
      healing are emerging. Reports about wound healing modulation by local application
      of simple and natural agents abound even in the recent literature, however, most
      are anecdotal and lack solid scientific evidence. We describe the effect of
      silver sulfadiazine and moist exposed burn ointment (MEBO), a recently described
      burn ointment of herbal origin, on mast cells and several wound healing cytokines
      (bFGF, IL-1, TGF-beta, and NGF) in the rabbit experimental burn model. The
      results demonstrate that various inflammatory cells, growth factors and cytokines
      present in the wound bed may be modulated by application of local agents with
      drastic effects on their expression dynamics with characteristic temporal and
      spatial regulation and changes in the expression pattern. Such data are likely to
      be important for the development of novel strategies for wound healing since they
      shed some light on the potential formulations of temporally and combinatory
      optimized therapeutic regimens.

PMID- 17521822
TI  - Endocytic trafficking signals in KCNMB2 regulate surface expression of a large
      conductance voltage and Ca(2+)-activated K+ channel.
AB  - Large conductance voltage and calcium-activated K(+) channels play critical roles
      in neuronal excitability and vascular tone. Previously, we showed that
      coexpression of the transmembrane beta2 subunit, KCNMB2, with the human pore
      forming alpha subunit of the large conductance voltage and Ca(2+)-activated K(+)
      channel (hSlo) yields inactivating currents similar to those observed in
      hippocampal neurons [Hicks GA, Marrion NV (1998) Ca(2+)-dependent inactivation of
      large conductance Ca(2+)-activated K(+) (BK) channels in rat hippocampal neurones
      produced by pore block from an associated particle. J Physiol (Lond) 508 (Pt
      3):721-734; Wallner M, Meera P, Toro L (1999b) Molecular basis of fast
      inactivation in voltage and Ca(2+)-activated K(+) channels: A transmembrane beta
      subunit homolog. Proc Natl Acad Sci U S A 96:4137-4142]. Herein, we report that
      coexpression of beta2 subunit with hSlo can also modulate hSlo surface expression
      levels in HEK293T cells. We found that, when expressed alone, beta2 subunit
      appears to reach the plasma membrane but also displays a distinct intracellular
      punctuated pattern that resembles endosomal compartments. beta2 Subunit
      coexpression with hSlo causes two biological effects: i) a shift of hSlo's
      intracellular expression pattern from a relatively diffuse to a distinct
      punctated cytoplasmic distribution overlapping beta2 expression; and ii) a
      decrease of hSlo surface expression that surpassed an observed small decrease in
      total hSlo expression levels. beta2 Site-directed mutagenesis studies revealed
      two putative endocytic signals at the C-terminus of beta2 that can control
      expression levels of hSlo. In contrast, a beta2 N-terminal consensus endocytic
      signal had no effect on hSlo expression levels. Thus, beta2 subunit not only can
      influence hSlo currents but also has the ability to limit hSlo surface expression
      levels via an endocytic mechanism. This new mode of beta2 modulation of hSlo may
      depend on particular coregulatory mechanisms in different cell types.

PMID- 17521823
TI  - Opioid modulation of reflex versus operant responses following stress in the rat.
AB  - In pre-clinical models intended to evaluate nociceptive processing, acute stress
      suppresses reflex responses to thermal stimulation, an effect previously
      described as stress-induced "analgesia." Suggestions that endogenous opioids
      mediate this effect are based on demonstrations that stress-induced hyporeflexia
      is enhanced by high dose morphine (>5 mg/kg) and is reversed by naloxone.
      However, reflexes and pain sensations can be modulated differentially. Therefore,
      in the present study direct comparisons were made of opioid agonist and
      antagonist actions, independently and in combination with acute restraint stress
      in Long Evans rats, on reflex lick-guard (L/G) and operant escape responses to
      nociceptive thermal stimulation (44.5 degrees C). A high dose of morphine (>8
      mg/kg) was required to reduce reflex responding, but a moderate dose of morphine
      (1 mg/kg) significantly reduced escape responding. The same moderate dose (and
      also 5 mg/kg) of morphine significantly enhanced reflex responding. Naloxone (3
      mg/kg) significantly enhanced escape responding but did not affect L/G
      responding. Restraint stress significantly suppressed L/G reflexes (hyporeflexia)
      but enhanced escape responses (hyperalgesia). Stress-induced hyperalgesia was
      significantly reduced by morphine and enhanced by naloxone. In contrast, stress
      induced hyporeflexia was blocked by both naloxone and 1 mg/kg of morphine. Thus,
      stress-induced hyperalgesia was opposed by endogenous opioid release and by
      administration of morphine. Stress-induced hyporeflexia was dependent upon
      endogenous opioid release but was counteracted by a moderate dose of morphine.
      These data demonstrate a differential modulation of reflex and operant outcome
      measures by stress and by separate or combined opioid antagonism or
      administration of morphine.

PMID- 17521824
TI  - A novel role for Fyn: change in sphere formation ability in murine embryonic stem
      cells.
AB  - Fyn, a member of the Src-family protein tyrosine kinase (PTK), is an essential
      factor in myelination in the CNS and is involved in murine embryonic stem (ES)
      cell growth and differentiation. Although dysfunctions of Fyn have been
      comparatively studied, the gain of function by ectopic expression, especially
      using ES cells, has seldom been investigated. In this article, we give the first
      report of the involvement of Fyn alteration in the sphere formation ability of
      murine ES cells. First, transient transfection of Fyn hardly affected
      multiplication and specialization. Then, we investigated Fyn overexpression using
      ES cells, which stably express Fyn. As a result, altered sphere formation
      capability was observed in all clones stably expressing Fyn. These results may
      provide important information for reproduction medical treatment using ES cells.

PMID- 17521826
TI  - Long-term memory consolidation depends on proteasome activity in the crab
      Chasmagnathus.
AB  - Long-term memory formation depends on protein and mRNA synthesis that subserves
      synaptic reorganization. The removal of pre-existing inhibitory proteins by the
      ubiquitin-proteasome system (UPS) is proposed as a crucial step to support these
      modifications. The activation of the constitutive transcription factor nuclear
      factor kappaB (NF-kappaB) depends on the degradation of the inhibitor of NF
      kappaB (IkappaB) by the UPS. Here we study the effect of a UPS inhibitor, MG132,
      on long-term memory consolidation and NF-kappaB activation in the learning
      paradigm of the crab Chasmagnathus, a model in which this transcription factor
      plays a key role. Here we found that administration of MG132 interferes with long
      term memory but not with short-term memory, and no facilitatory effects were
      found. Then we studied the effect of the UPS inhibitor on NF-kappaB pathway,
      finding that MG132 blocks the activation of NF-kappaB induced by training. These
      results suggest that the UPS is necessary for long-term memory consolidation,
      allowing for the activation of NF-kappaB as one of the target molecular pathways.

PMID- 17521827
TI  - Retinoic acids acting through retinoid receptors protect hippocampal neurons from
      oxygen-glucose deprivation-mediated cell death by inhibition of c-jun-N-terminal
      kinase and p38 mitogen-activated protein kinase.
AB  - Retinoic acids (RAs), including all-trans retinoic acid (ATRA) and 9-cis retinoic
      acid (9-cis RA), play fundamental roles in a variety of physiological events in
      vertebrates, through their specific nuclear receptors: retinoic acid receptor
      (RAR) and retinoid X receptor (RXR). Despite the physiological importance of RA,
      their functional significance under pathological conditions is not well
      understood. We examined the effect of ATRA on oxygen/glucose
      deprivation/reperfusion (OGD/Rep)-induced neuronal damage in cultured rat
      hippocampal slices, and found that ATRA significantly reduced neuronal death. The
      cytoprotective effect of ATRA was observed not only in cornu ammonis (CA) 1 but
      also in CA2 and dentate gyrus (DG), and was attenuated by selective antagonists
      for RAR or RXR. By contrast, in the CA3 region, no protective effects of ATRA
      were observed. The OGD/Rep also increased phosphorylated forms of c-jun-N
      terminal kinase (P-JNK) and p38 (P-p38) in hippocampus, and specific inhibitors
      for these kinases protected neurons. ATRA prevented the increases in P-JNK and P
      p38 after OGD/Rep, as well as the decrease in NeuN and its shrinkage, all of
      which were inhibited by antagonists for RAR or RXR. These findings suggest that
      the ATRA signaling via retinoid receptors results in the inhibition of JNK and
      p38 activation, leading to the protection of neurons against OGD/Rep-induced
      damage in the rat hippocampus.

PMID- 17521830
TI  - Cytosine methylation is associated with RNA silencing in silenced plants but not
      with systemic and transitive RNA silencing through grafting.
AB  - RNA silencing is often associated with methylation of the target gene. The DNA
      methylation level of transgenes was investigated in post-transcriptionally
      silenced or non-silenced Nicotiana benthamiana carrying either the 5' region (200
      or 400 bp) or the entire region of the coat protein gene (CP, including the 3'
      non-translated region) of Sweet potato feathery mottle virus. Higher levels of
      transgene cytosine methylation were observed in both symmetrical (CpG, CpNpG) and
      non-symmetrical (CpHpH) contexts (CpG>CpNpG>CpHpH) in silenced lines, but there
      was very lower levels or no transgene methylation in non-silenced lines. RNA
      silencing was induced in non-silenced scions from silenced rootstocks and spread
      to the 3' region of the transgene mRNA (Haque et al., Plant Mol. Biol. 2007; 63:
      35-47). In this system, transgene methylation levels were analyzed in scions at
      different time intervals after being grafted onto silenced or non-silenced
      rootstocks to investigate if transgene methylation was associated with induction
      or transitivity of RNA silencing. We observed that, there was no change of
      transgene methylation level in the initial target or in extended regions in
      scions. These results showed that transgene methylation was associated with RNA
      silencing in individual transformants, but it was not associated with systemic
      RNA silencing and/or transitive RNA silencing through grafting.

PMID- 17521829
TI  - Cerebral metabolism and mood in remitted opiate dependence.
AB  - BACKGROUND: Opiate-dependent individuals are prone to dysphoria that may
      contribute to treatment failure. Methadone-maintenance therapy (MMT) may mitigate
      this vulnerability, but controversy surrounds its long-term use. Little is known
      about the neurobiology of mood dysregulation in individuals receiving or removed
      from MMT. METHODS: Fifteen opiate-abstinent and 12 methadone-maintained, opiate
      dependent subjects, who lacked other Axis I pathology, and 13 control subjects
      were compared on the Cornell Dysthymia Rating Scale (CDRS) and regional cerebral
      glucose metabolism (rCMRglc) using [(18)F]fluorodeoxyglucose positron emission
      tomography. RESULTS: CDRS scores showed no group differences. Opiate-abstinent
      subjects had lower rCMRglc than control subjects in the bilateral perigenual
      anterior cingulate cortex (ACC), left mid-cingulate cortex, left insula and right
      superior frontal cortex. Methadone-maintained subjects exhibited lower rCMRglc
      than control subjects in the left insula and thalamus. In opiate-abstinent
      subjects, rCMRglc in the left perigenual ACC and mid-cingulate cortex correlated
      positively with CDRS scores. CONCLUSIONS: In remitted heroin dependence, opiate
      abstinence is associated with more widespread patterns of abnormal cortical
      activity than MMT. Aberrant mood processing in the left perigenual ACC and mid
      cingulate cortex, seen in opiate-abstinent individuals, is absent in those
      receiving MMT, suggesting that methadone may improve mood regulation in this
      population.

PMID- 17521831
TI  - Rapid testing leads to the underestimation of the scrapie prevalence in an
      affected sheep and goat flock.
AB  - To obtain a more detailed understanding of the prevalence of classical scrapie
      infections in a heavily affected German sheep flock (composed of 603 sheep and 6
      goats), we analysed 169 sheep and 6 goats that carried the genotypes susceptible
      to the disease and that were therefore culled following discovery of the index
      case. The initial tests were performed using the Biorad TeSeE ELISA and reactive
      results were verified by official confirmatory methods (OIE-immunoblot and/or
      immunohistochemistry (IHC)) to demonstrate the deposition of scrapie-associated
      PrP(Sc) in the brain stem (obex). This approach led to the discovery of 40
      additional subclinically scrapie-infected sheep. Furthermore, peripheral
      lymphatic and nervous tissue samples of the 129 sheep and 6 goats with a negative
      CNS result were examined by IHC in order to identify any preclinical infections
      which had not already spread to the central nervous system (CNS). Using this
      approach we found 13 additional sheep with PrP(Sc) depositions in the gut
      associated lymph nodes (GALT) as well as in the enteric nervous system. Moreover,
      in most of these cases PrP(Sc) was also deposited in the spleen and in the
      retropharyngeal and superficial cervical lymph nodes. Taken together, these
      results show a 30.3% infection prevalence in this scrapie-affected flock. Almost
      7.4% of the infected animals harboured PrP(Sc) exclusively in the peripheral
      lymphatic and nervous tissue and were therefore missed by the currently used
      testing strategy.

PMID- 17521832
TI  - Molecular epidemiology of bluetongue virus in Portugal during 2004-2006 outbreak.
AB  - After 44 years of epidemiological silence, bluetongue virus (BTV) was
      reintroduced in Portugal in the autumn of 2004. The first clinical cases of
      bluetongue disease (BT) were notified in sheep farms located in the South of
      Portugal, close to the Spanish border. A total of six BTV, five of serotype 4 and
      one of serotype 2 were isolated from sheep and cattle during the 2004-2006
      epizootics. The nucleotide sequence of gene segments L2, S7 and S10 of BTV-4
      prototype strain (BTV4/22045/PT04) obtained from the initial outbreak and of BTV
      2 (BTV2/26629/PT05) was fully determined and compared with those from other parts
      of the world. The phylogenetic analysis revealed that BTV4/22045/PT04 is related
      to other BTV-4 strains that circulate in the Mediterranean basin since 1998,
      showing the highest identity (99%) with BTV-4 isolates of 2003 from Sardinia and
      Corsica, whereas BTV2/26629/PT05 is almost indistinguishable from the
      Onderstepoort BTV-2 live-attenuated vaccine strain and its related field strain
      isolated in Italy. Since live-attenuated BTV-2 vaccine was never used in
      Portugal, the isolation of this strain may represent a natural circulation of the
      vaccine virus used in other countries in Mediterranean Europe.

PMID- 17521833
TI  - Characteristics of extended-spectrum cephalosporin-resistant Escherichia coli and
      Klebsiella pneumoniae isolates from horses.
AB  - The aim of the present study was to contribute to the knowledge on extended
      spectrum beta-lactamases (ESBL's), AmpC beta-lactamases and integrons in
      Enterobacteriaceae isolated from horses, which is still limited. The
      susceptibility of 1581 clinical isolates from animals to ceftiofur was tested.
      Most of these isolates (n=1347) originated from horses. Seven ceftiofur-resistant
      equine isolates (four Escherichia coli and three Klebsiella pneumoniae) were
      identified and all seven were multidrug-resistant. These isolates were further
      studied for the presence of ESBL's, AmpC beta-lactamases and class 1 integrons.
      The potential for the horizontal transfer of resistance genes among these
      clinical isolates was also studied. ESBL-type resistance genes were found in five
      isolates, AmpC-type genes in one isolates and integrons in six isolates.
      Nucleotide sequence analysis revealed that the isolates carried the bla(CTX-M-1),
      bla(CMY-2), bla(TEM-1) and/or bla(SHV-1) genes. This is the first report
      describing the in vitro conjugal transfer of the bla(CTX-M-1) genes from a
      clinical E. coli isolate to Salmonella isolates. Gene cassettes encoding
      resistance to aminoglycosides (aadA1, aadA2 and aadA5), and trimethoprim (dfrA1,
      drfA12 and dfrA17) were found on the integrons present in the isolates. The
      cassette arrays of the dfrA17-aadA5 and dfrA1-aadA1 genes in the two integrons of
      a single E. coli isolate have not yet been described before. To our knowledge
      this is the first report on ESBL's and AmpC beta-lactamases in equine E. coli and
      Klebsiella isolates.

PMID- 17521834
TI  - Intra-vesicle administration of D-cloprostenol for induction of abortion in mid
      gestation bitches.
AB  - This study evaluated a new method for mid-gestation termination in the bitch,
      which consisted of ultrasound-guided administration of a single dose of d
      cloprostenol, a PGF(2alpha) analogue, into a single gestational sac. Effects on
      serum progesterone concentration (P(4)) were also investigated. The study was
      performed between days 28 and 35 of gestation on 15 privately owned crossbred
      bitches, randomly divided into two groups: group A comprised 10 bitches treated
      with 15 microg per head d-cloprostenol diluted in 0.8 ml sterile saline (final
      volume 1 ml); group B comprised 5 bitches treated with 1 ml of sterile saline
      solution (0.9% NaCl), administered in the same way. In all bitches of group A,
      fetal death was successfully induced within 5 days (mean: 3.1 days, S.D. 1.2)
      with no clinical or behavioural complications. Mild adverse effects were observed
      in two bitches, each weighing less than 10 kg, including salivation, defecation
      and hyperventilation, which disappeared within 15 min. None of the subjects in
      group B aborted within 10 days post-treatment. In group A, P(4) declined 2.8 days
      before pregnancy termination to a mean value below 30 nmol/l (S.D. 2.9 nmol/l).
      However, two bitches showed a higher concentration of P(4) throughout the
      sampling period. Our study demonstrates that intra-vesicle administration of a
      single low dose of D-cloprostenol is an effective and safe technique for
      induction of abortion, which offers an additional option for termination of
      unwanted pregnancy in the mid-gestation bitch.

PMID- 17521835
TI  - Relationship between follicle growth and circulating gonadotrophin levels during
      postnatal development of sheep.
AB  - This study investigates the number and size of ovarian antral follicles in
      relation to plasma follicle stimulating hormones (FSH) and luteinizing hormone
      (LH) concentrations from birth to 26 weeks of age in ewe lambs of the Ouled
      Djellel breed, a non-seasonal breed of sheep. Plasma was collected from 10 ewe
      lambs at 14 sampling times (Week 0, i.e. <24h, Week 1 and every two weeks from
      Week 4 to Week 26, inclusive). At each of these stages, four ewe lambs were
      slaughtered, the ovaries recovered and weighed, and the number and size of the
      follicles determined from histological examination. The pattern for plasma FSH
      showed a peak at Week 10, a smaller peak at Week 18 and a very small peak at Week
      24. The pattern for LH was similar until Week 24 when the largest peak occurred.
      Paired ovarian weight increased rapidly from birth to four weeks and then more
      slowly to 10 weeks, followed by a decline at 12 weeks and a gradual increase from
      14 to 24 weeks of age. The number and total diameter of follicles > or =3 mm in
      diameter showed similar patterns of development--rising gradually from birth to
      Week 14, falling to Week 16 and then rising more rapidly to a peak at Week 24.
      Maximum follicle diameter declined from birth to Week 1, then rose rapidly to
      Week 4, followed by a more gradual rise to Week 14 and, thereafter, a more rapid
      increase to a peak of 7.23+/-0.16 mm at 24 weeks old. The number of follicles (<3
      mm diameter) increased rapidly from birth to Week 10 and then declined to values
      similar to those at Weeks 1 and 4. First behavioural oestrus was observed at Week
      24 and a corpus luteum was present on the ovary of one lamb at Week 24 and two
      lambs at Week 26. It was concluded that two or three peaks in plasma FSH and LH
      levels precede puberty and first ovulation in Ouled Djellel ewe lambs, and first
      ovulation occurred at 24-26 weeks of age. The increase in follicle number and
      size generally reflected the pattern of plasma FSH and LH levels.

PMID- 17521836
TI  - Quality by design: characterization of self-nano-emulsified drug delivery systems
      (SNEDDs) using ultrasonic resonator technology.
AB  - In the present work, a novel application of ultrasonic measurements is detailed
      to characterize nano-emulsion formulations as a part of the overall Quality by
      Design (QbD) goal. Ultrasonic resonator technology (URT) was utilized to measure
      sound velocity and absorption of self-nanoemulsified drug delivery systems
      (SNEDDs) consisting of various ratios of oil:surfactant:co-surfactant. A QbD
      concept was used to create different SNEDDs formulations utilizing sweet orange
      oil (oil), Emulphor-620 (surfactant), and Capmul (co-surfactant) by dissolving
      Cyclosporine A in oil. The mixture was emulsified in water and ultrasonic
      measurements were carried out in an ultrasonic resonator system isothermally for
      a period of about 15-20min. Compressibility of the individual components in the
      droplets, hydration of the droplets and the influence of the composition on
      droplet stability were studied by systematic ultrasonic measurements at a single
      resonator frequency. The adiabetic compressibilities for the oil, aqueous and
      interfacial components were 68, 44.6, and 53 [10(-11)Pa(-1)], respectively as
      calculated using Urick's equation. Also the ultrasonic absorption correlated
      droplet size of nano-emulsions linearly with R(2) of 0.84 indicating this can be
      used as an additional technique to measure the droplet size of nano-emulsions.
      Correlation of ultrasonic data with formulation components indicated that the
      ultrasonic velocity correlated negatively with increasing oil amount in the
      formulation as well as surfactant-to-cosurfactant ratios where as droplet
      diameter correlated positively with these formulation factors. It can be
      envisioned from the results that the compressibility of the media increases with
      the addition of the oily component and thus reducing the sound velocity. Thus URT
      enabled direct and convenient analysis of the physical properties as well as
      influence of formulation factors of nano-emulsions which is an important
      indication of stability of these nano-emulsions.

PMID- 17521837
TI  - Survival and stimulation of neurite outgrowth in a serum-free culture of spiral
      ganglion neurons from adult mice.
AB  - We have developed a reliable protocol for the serum-free dissociation and culture
      of spiral ganglion neurons from adult mice, an important animal model for
      patients with post-lingual hearing loss. Pilot experiments indicated that the
      viability of spiral ganglion cells in vitro depended critically on the use of
      Hibernate medium with B27 supplement. With an optimized protocol, we obtained 2 x
      10(3) neurons immediately after dissociation, or about one-fifth of those present
      in the intact spiral ganglion. After four days in culture, 4% of the seeded
      neurons survived without any exogenous growth factors other than insulin. This
      yield was highly reproducible in five independent experiments and enabled us to
      measure systematically the numbers and lengths of the regenerating neurites.
      Furthermore, the survival rate compared well to the few published protocols for
      culturing adult spiral ganglion neurons from other species. Enhanced survival and
      neurite outgrowth upon the addition of brain-derived neurotrophic factor and
      leukemia inhibitory factor demonstrated that both are potent stimulants for
      damaged spiral ganglion neurons in adults. This responsiveness to exogenous
      growth factors suggested that our culture protocol will facilitate the screening
      of molecular compounds as potential treatments for sensorineural hearing loss.

PMID- 17521838
TI  - [Pilot campaign to promote vaccination: description preliminary results of a
      regional French program].
AB  - CONTEXT AND OBJECTIVE: In 2003, the Franche-Comte decided to launch an innovating
      program, with the support of many national partners. The objective was to improve
      the vaccine coverage of Franche-Comte population. DESCRIPTION OF THE
      INTERVENTION: It consisted in organizing every year (for three years) a week of
      vaccination with the active assistance of community healthcare professionals
      (doctors, pharmacists, etc.) and to develop complementary activities during the
      year: media campaign, visits to all local physicians, training, written data
      (posters, booklets, etc.), implementing an exhibition. RESULTS: This program is
      not yet finished. However, the first results (after two years) are very
      encouraging. Several types of evaluation were carried out: 1) PROCESS: inquiry
      with physicians; 2) IMPACT: follow-up of vaccine refunding evolution. The
      notoriety of the program seems important with physicians. They declared having
      changed their vaccination behavior with their patients. After the vaccination
      week, the number of vaccines refunded in the next 2 months (compared to the same
      reference period in 2003) increased by 10% in 2005, after a first increase of 5%
      in 2004. DISCUSSION/CONCLUSION: The initial analysis confirms that the impact of
      "a vaccination week" seems to reinforce regional vaccine coverage. Moreover, WHO
      Europe and the French Health Ministry have decided to extend this program to the
      national level in 2007.

PMID- 17521839
TI  - Association between Helicobacter pylori genotypes and gastric disorders in
      relation to the cag pathogenicity island.
AB  - Helicobacter pylori is a bacterium associated with upper gastrointestinal
      diseases in humans. However, only a small proportion of infected people become
      sick. Although several studies have tried to establish an association between
      known virulence markers and clinical outcomes, in many cases the results have
      been conflicting. The aim of this study was to investigate the importance of
      virulence markers to predict clinical outcome in Brazil. Mixed infections by
      genetically unrelated strains detected by vacA genotyping were found in 18% of
      the patients. The cagA and cagE genes and the vacAs1 genotype were associated
      with the development of peptic ulcer disease (PUD). The cagAvacAs1m1 genotype was
      associated with PUD and duodenal ulcer (DU). Conversely, jhp947 was not
      associated with DU or PUD, indicating that this gene is not a universal virulence
      marker. These results also show that a high proportion of the patients were
      simultaneously infected by cag-positive and cag-negative H. pylori types. This
      finding suggests the existence of a dynamic equilibrium between the loss and gain
      of the cag pathogenicity island, probably depending on the physiologic conditions
      of the patient's stomach. To the best of our knowledge, this is the first study
      that has documented this finding in Brazil.

PMID- 17521840
TI  - Molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa carrying
      metallo-beta-lactamase genes in Taiwan.
AB  - Seventy-two isolates of carbapenem-resistant Pseudomonas aeruginosa (CRPA)
      collected through the Taiwan Surveillance of Antimicrobial Resistance (TSAR)
      program in 2000 and 2002 were studied for carriage of metallo-beta-lactamase
      (MBL), integrase genes, and integrons. Epidemiologic relatedness was determined
      using pulsed-field gel electrophoresis. The prevalence of the MBL genes among
      CRPA was 36.0% (9 of 25) in TSAR II and 17.0% (8/47) in TSAR III, with prevalence
      in surveyed hospitals being 19.1% (4/21, TSAR II) and 23.1% (6 of 26, TSAR III).
      The bla(VIM-3) was detected in 15 of the 17 MBL-positive isolates; the remainder
      possessed bla(VIM-2). The bla(IMP) was not evident. Class 1 integron was detected
      in all MBL-positive isolates; amplicon DNA sequences containing the bla(VIM-3)
      regions were all identical. All MBL-positive isolates remained susceptible to
      colistin. Molecular typing revealed a predominant strain that comprised 14 of the
      isolates among the various surveyed hospitals.

PMID- 17521841
TI  - Presentation of eating disorders in the news media: What are the implications for
      patient diagnosis and treatment?
AB  - OBJECTIVE: Eating disorder (ED) specialists increasingly see anorexia nervosa and
      bulimia nervosa as complex mental illnesses with both genetic and social roots.
      The public, however, tends to view EDs more simply as a manifestation of personal
      or social problems among female, white, young women. This disconnect potentially
      prevents timely ED diagnosis and reinforces a stigma that limits treatment
      availability. We examine the presentation of EDs in daily newspapers, an
      important contributor to shaping public perception of EDs. METHODS: We analyze 1
      year of coverage about EDs by seven daily U.S. newspapers (252 articles),
      focusing on the messages conveyed about epidemiology, etiology, severity and
      treatment. RESULTS: The highest proportion of articles about EDs (48%) ran in
      arts and entertainment sections. Articles primarily covered those who are female,
      young and white, and mentioned mainly environmental causal factors. Only 8% of
      patient profiles discussed treatment and recovery within a medical context.
      CONCLUSION: News coverage rarely presents EDs as complex medical phenomena, but
      rather simplifies and sensationalizes these conditions. PRACTICE IMPLICATIONS:
      Educators would benefit from recognizing the news media's role in shaping public
      perceptions of EDs in ways that differ from clinical perspectives, potentially
      limiting diagnosis and treatment. Three communication improvements are suggested.

PMID- 17521842
TI  - The impact of informational interventions about cognitive behavioral therapy for
      chronic fatigue syndrome on GPs referral behavior.
AB  - OBJECTIVE: This study investigated the impact of an informational intervention
      among general practitioners (GPs) about a new treatment with cognitive behavioral
      therapy (CBT) for chronic fatigue syndrome (CFS) in a mental health center (MHC).
      The outcome measures concerned GPs knowledge and attitudes towards CFS and their
      actual referrals of CFS patients to this new treatment setting. METHODS: Three
      hundred and one GPs, who all had received written information about CFS four
      times, and who partly had also visited an informational group session, completed
      a short questionnaire survey on CFS knowledge and attitudes. Referral data were
      obtained from the mental health center. RESULTS: During 16 months 22% of all GPs
      in the concerning region had referred at least one CFS patient. Concerning
      knowledge and attitude, the survey results showed that 70% of the GPs had
      remembered the intervention's main message, namely the new treatment possibility.
      These informed GPs reported better knowledge and more positive attitudes towards
      CFS than the non-informed GPs, who had not seen and read the intervention's
      information. CONCLUSION: This study showed that disseminating written materials
      can be a useful method for stimulating GPs to refer CFS patients for CBT.
      PRACTICE IMPLICATIONS: In future implementation projects concerning CBT for CFS
      (or other 'new' treatments for a disputed illness) in a MHC or other institution,
      the informational intervention evaluated here can be a suitable and efficient
      method to inform GPs and let them refer patients.

PMID- 17521843
TI  - Rates of ethanol metabolism decrease in sons of alcoholics following a priming
      dose of ethanol.
AB  - Rapid changes in rates of ethanol metabolism in response to acute ethanol
      administration have been observed in animals and humans. To examine whether this
      phenomenon might vary by risk for alcoholism, 23 young men with a positive family
      history of alcoholism (family history positive [FHP]) were compared to 15 young
      men without a family history of alcoholism (family history negative [FHN]). Rates
      of ethanol metabolism were measured in all subjects first after an initial
      ethanol dose (0.85 g/kg) and then, several hours later, a second dose (0.3 g/kg),
      and the two rates were compared. The two groups of subjects were similar in their
      histories of ethanol consumption. FHP subjects demonstrated faster initial rates
      of ethanol metabolism, 148+/-36 mg/kg/h, compared to FHN subjects, 124+/-18
      mg/kg/h, P=.01. However, FHN subjects increased their rate of metabolism by 10+/
      27% compared to a decrease of -15+/-24% in FHP subjects, P=.007. Fifty-two
      percent of the FHP and none of the FHN subjects exhibited a decline in metabolic
      rate of 20% or more, P=.0008. Since a significant proportion of FHP subjects
      exhibited a decrease in the second rate of ethanol metabolism, these preliminary
      data might help to partly explain why FHP individuals differ in their sensitivity
      to ethanol and are more likely to develop alcohol dependence.

PMID- 17521844
TI  - Tonic for what ails us? high-affinity GABAA receptors and alcohol.
AB  - Ethanol interactions with gamma-aminobutyric acid (GABA), the major inhibitory
      neurotransmitter in the brain, play key roles in acute intoxication. However, the
      exact mechanisms of these ethanol interactions have been the subject of
      considerable confusion and controversy. Many studies suggest that ethanol
      potentiates the function of the type A GABA receptor (GABAA-R). However, these
      findings have not been consistently replicated in experiments that directly
      examined the effects of ethanol on GABAA-R-mediated ion current. Differences in
      ethanol sensitivity of different GABAA-R subtypes have been invoked as a
      potential explanation for the inconsistent findings, and recent work suggests
      that GABAA-Rs that contain the delta subunit and/or mediate tonic extrasynaptic
      GABA responses may be especially ethanol sensitive. However, considerable
      disagreement has arisen over these findings. This special issue of Alcohol
      contains articles from eight research groups that are examining this issue. The
      authors present their work, their views on the present state of this area of
      alcohol research, and their ideas about how to proceed with future studies that
      may help to address the present confusion and controversy. This editorial
      provides an introduction to this line of research and the current findings and
      controversies.

PMID- 17521845
TI  - Studies of ethanol actions on recombinant delta-containing gamma-aminobutyric
      acid type A receptors yield contradictory results.
AB  - The gamma-aminobutyric acid type A receptors (GABAA-Rs) display a wide variety of
      subunit combinations. Drugs such as benzodiazepines have shown differential
      effects based on GABAA-R subunit composition. Actions of alcohols and volatile
      anesthetics generally do not vary markedly with subunit composition, with low
      concentrations of ethanol being poor modulators of these receptors. Recent
      studies showed alpha(4/6)- and delta-containing GABAA-Rs (located
      extrasynaptically and responsible for tonic currents in selective brain regions)
      presenting high sensitivity to low concentrations of ethanol, but these results
      have not been obtained in other laboratories. We carried out additional
      experiments varying the receptor level of expression, and GABA and ethanol
      concentration, but no sensitivity to low concentrations of ethanol was detected.
      We will discuss these results and attempt an analysis of the possible causes for
      the discrepancies.

PMID- 17521846
TI  - A new meaning for "Gin & Tonic": tonic inhibition as the target for ethanol
      action in the brain.
AB  - Gamma-aminobutyric acid (GABA) is the main chemical inhibitory neurotransmitter
      in the brain. In the central nervous system, it acts on two distinct types of
      receptor: an ion channel, that is, an "ionotropic" receptor permeable to Cl- and
      HCO3- (GABAA receptors [GABAARs]) and a G-protein coupled "metabotropic" receptor
      that is linked to various effector mechanisms (GABAB receptors). This review will
      summarize novel developments in the physiology and pharmacology of GABAARs,
      specifically those found outside synapses. The focus will be on a particular
      combination of GABAAR subunits responsible for mediating tonic inhibition and
      sensitive to concentrations of ethanol legally considered to be sobriety
      impairing. Since the same receptors are also a preferred target for the
      metabolites of steroid hormones synthesized in the brain (neurosteroids), the
      ethanol-sensitive tonic inhibition may be a common pathway for interactions
      between the effects of alcohol and those of ovarian and stress-related
      neurosteroids.

PMID- 17521848
TI  - GABAA receptors in the thalamus: alpha4 subunit expression and alcohol
      sensitivity.
AB  - The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has long been
      implicated in the anxiolytic, amnesic, and sedative behavioral effects of
      alcohol. A large number of studies have investigated the interactions of alcohol
      with GABA receptors. Many investigators have reported effects of "high
      concentrations" (50-100 mM) of alcohol on GABA-mediated synaptic inhibition, but
      effects of the "low concentrations" (1-30 mM) of alcohol normally associated with
      mild intoxication have been elusive until recently. A novel form of "tonic
      inhibition" has been described in the central nervous system (CNS) that is
      generated by the persistent activation of extrasynaptic gamma-aminobutyric acid
      type A receptors (GABAA-Rs). These receptors are specific GABAA-R subtypes and
      distinct from the synaptic subtypes. Tonic inhibition regulates the excitability
      of individual neurons and the activity and rhythmicity of neural networks.
      Interestingly, several reports show that tonic inhibition is sensitive to low
      concentrations of alcohol. The thalamus is a structure that is critically
      important in the control of sleep and wakefulness. GABAergic inhibition in the
      thalamus plays a crucial role in the generation of sleep waves. Among the various
      GABAA-R subunits, the alpha1, alpha4, beta2, and delta subunits are heavily
      expressed in thalamic relay nuclei. Tonic inhibition has been demonstrated in
      thalamocortical relay neurons, where it is mediated by alpha4beta2delta GABAA-Rs.
      These extrasynaptic receptors are highly sensitive to gaboxadol, a novel
      hypnotic, but insensitive to benzodiazepines. Tonic inhibition is absent in
      thalamic relay neurons from alpha4 knockout mice, as are the sedative and
      analgesic effects of gaboxadol. The sedative effects of alcohol can promote
      sleep. However, alcohol also disrupts the normal sleep pattern and reduces sleep
      quality. As a result, sleep disturbance caused by alcohol can play a role in the
      progression of alcoholism. As an important regulator of sleep cycles, inhibition
      in the thalamus may therefore be involved in both the sedative effects of alcohol
      and the development of alcoholism. Investigating the effects of alcohol on both
      synaptic and extrasynaptic GABAA-Rs in the thalamus should help us to understand
      the mechanisms underlying the interaction between alcohol and sleep.

PMID- 17521847
TI  - Modulation of GABAA receptors in cerebellar granule neurons by ethanol: a review
      of genetic and electrophysiological studies.
AB  - Cerebellar granule neurons (CGNs) receive inhibitory input from Golgi cells in
      the form of phasic and tonic currents that are mediated by postsynaptic and
      extrasynaptic gamma-aminobutyric acid type A (GABAA) receptors, respectively.
      Extrasynaptic receptors are thought to contain alpha6betaxdelta subunits. Here,
      we review studies on ethanol (EtOH) modulation of these receptors, which have
      yielded contradictory results. Although studies with recombinant receptors
      expressed in Xenopus oocytes indicate that alpha6beta3delta receptors are
      potently enhanced by acute exposure to low (>or=3 mM) EtOH concentrations, this
      effect was not observed when these receptors were expressed in Chinese hamster
      ovary cells. Slice recordings of CGNs have consistently shown that EtOH increases
      the frequency of phasic spontaneous inhibitory postsynaptic currents (sIPSCs), as
      well as the tonic current amplitude and noise. However, there is a lack of
      consensus as to whether EtOH directly acts on extrasynaptic receptors or
      modulates them indirectly; that is, via an increase in spillover of synaptically
      released GABA. It was recently demonstrated that an R to Q mutation of amino acid
      100 of the alpha6 subunit increases the effect of EtOH on both sIPSCs and tonic
      current. These electrophysiological findings have not been reproducible in our
      hands. Moreover, it was shown the alpha6-R100Q mutation enhances sensitivity to
      the motor-impairing effects of EtOH in outbred Sprague-Dawley rats, but this was
      not observed in a line of rats selectively bred for high sensitivity to EtOH
      induced motor alterations (Alcohol Non-Tolerant rats). We conclude that currently
      there is insufficient evidence conclusively supporting a direct potentiation of
      extrasynaptic GABAA receptors following acute EtOH exposure in CGNs.

PMID- 17521849
TI  - Ethanol levels in honeybee hemolymph resulting from alcohol ingestion.
AB  - Our previous work on a social insect model of ethanol-induced behavior focused on
      behavioral studies of honeybees (Apis mellifera L.). We now investigate the
      dependence of honeybee blood ethanol concentration on both the amount of ethanol
      consumed and time elapsed since ingestion. Blood ethanol level was determined
      using gas chromatograph using hemolymph taken from harnessed bees. Significantly
      increased levels of ethanol in honeybee hemolymph were detected within 15 min of
      feeding bees alcohol. Within 30 min, ethanol concentration increased 2.7 times.
      The concentration of ethanol ingested also had a significant effect on blood
      ethanol level. However, postfeeding times greater than 30 min did not
      significantly increase ethanol concentration in bee hemolymph. This study
      integrates with our behavioral data on the effect of ethanol on honeybees. Our
      laboratory and field experiments show a correlation between the time frame for
      behavioral changes and significant increases of blood ethanol levels shown in
      this study.

PMID- 17521850
TI  - Hospital volume does not affect clinical outcome.

PMID- 17521851
TI  - [Mortality and prognostic factors of the cirrhotic patients with hepatic
      encephalopathy admitted to medical intensive care unit].
AB  - OBJECTIVE: To assess mortality and to identify variables that could predict it in
      cirrhotic patients hospitalized to the medical intensive care unit (MICU) for
      hepatic encephalopathy (HE). STUDY DESIGN: Retrospective cohort study. PATIENTS
      AND METHODS: From January 1995 to December 2004, the cirrhotic patients admitted
      consecutively in MICU were screened and those with altered level of consciousness
      were included. The MICU mortality rate was assessed. Nearly 80 variables were
      analyzed and compared between survivors and non-survivors. STATISTICAL ANALYSIS:
      t test, chi(2) or Fisher exact tests, Kaplan-Meier and log rank, Cox regression
      analysis. RESULTS: A total of 180 patients (42 women-138 men, mean age: 59+/-10
      years) were admitted (incidence: 2.6%). The SAPS II was 30.1+/-11, Acute
      Physiology Age and Chronic Health Evaluation II (APACHE II): 16.5+/-5.3, Child
      Pugh score: 9.1+/-1.9 and GCS: 11+/-2.8. The causes of liver cirrhosis was
      identified in 41.2% of cases (viral: 35.6%, alcohol: 5.6%). Nearly 18% of
      patients had an antecedent of HE. The causes of HE were: infection (65.6%), upper
      gastrointestinal bleeding (32.2%), drugs (5%) and metabolic cause (5%). MICU
      mortality rate was 33.3% and seemed higher in gastrointestinal bleeding. Eighteen
      variables were significantly associated with poor prognosis in univariate
      analysis. Only three variables remained significant in multivariate analysis:
      systolic blood pressure<90 mmHg (RR=4; IC 95%=2-8.1), total WBC>12000 n/mm(3)
      (RR=3.1; IC 95%=1.8-5.3) and use of mechanical ventilation (RR=3.1; IC 95%=1.7
      5.6). CONCLUSION: The MICU mortality of cirrhotic patients with HE was high and
      significantly associated with haemodynamic instability, hyperleucocytosis and
      mechanical ventilation.

PMID- 17521852
TI  - [Anaesthetic agents in children: risk or benefit?].
AB  - The practice of paediatric anaesthesia has changed during the last 25 years, with
      a noticeable reduction of mortality and serious morbidity. This improvement
      results in part from the use of new anaesthetic agents which large therapeutic
      interval regarding cardiovascular effects. Parallel to this advance and following
      experimental or clinical studies in neurosciences, some new concerns have emerged
      regarding short and long time consequences of anaesthesia. Indeed, postoperative
      hyperalgesia due to opioids, emergence agitation and postoperative maladaptive
      behavioural changes are widely described in children, in the same way the
      potential epileptogenic effect of sevoflurane is demonstrated. Thus the
      hypothetical cerebral toxicity leads us to reconsider our practice. Basically,
      monitoring of cerebral cortical effects of hypnotics is now possible from
      automated devices based on EEG, allowing us to control the administration of
      hypnotic agents. The therapeutic interval of these agents, previously determined
      between movement at incision and deleterious cardiovascular effect, may be
      revisited with a cerebral approach, with the risk of memorisation for the lower
      limit and the risk of cerebral over dosage for the upper limit. Lastly, further
      experimental and clinical studies are required to analyse the effects of the
      anaesthetic agents on the brain of the neonate, and the interest of the cerebral
      monitoring in this population.

PMID- 17521853
TI  - [Timing of tracheostomy and outcome of patients requiring mechanical
      ventilation].
AB  - OBJECTIVES: To assess the impact of tracheostomy timing on outcome of critically
      ill patients requiring mechanical ventilation (MV). STUDY DESIGN: Retrospective
      clinical study in a twelve beds intensive care unit (ICU). PATIENTS AND METHODS:
      From January 2001 to June 2005, patients under MV who received tracheostomy were
      divided into 2 groups: early tracheostomy group when tracheostomy was performed
      before or on day 7 and late tracheostomy group when it was performed thereafter.
      We compared prevalence of nosocomial pneumonia, length of sedation, lengths of
      MV, length of stay in ICU, weaning from MV and mortality rates between the 2
      groups. RESULTS: During this period of 4 years and half, 112 patients underwent
      tracheostomy, 62 of whom had early tracheostomy and 50 had late tracheostomy.
      Early tracheostomy was associated with significant reduction of length of
      sedation (10+/-3 vs 17+/-5 days, P<0.001), length of MV (21+/-19 vs 29+/-17 days,
      P=0.02) and length of stay in ICU (33+/-22 vs 42+/-18 days, P=0.042). There were
      no differences in prevalence of pneumonia (21% for early tracheostomy group vs
      31% for late tracheostomy group, P=0, 13), weaning from MV (50 vs 36%, P=0.19),
      and mortality rates between the 2 groups (38 vs 54%, P=0.15). CONCLUSION: This
      study demonstrated that early tracheostomy (< or =7 days), was associated with
      shorter length of sedation, shorter duration of MV and shorter ICU length of
      stay, without affecting weaning from MV, prevalence of nosocomial pneumonia or
      survival.

PMID- 17521854
TI  - [Information before anaesthesia: a proposal for a new document].

PMID- 17521855
TI  - [Is there still a place for dopamine in the paediatric critical care setting?].
AB  - Dopamine is mostly used in patients with cardiogenic or septic shock, but its
      place in critical care medicine is often questioned. Dopamine, of which
      pharmacology in children is variable, is prescribed for its inotropic effect,
      associated with an increase in cardiac output and at a lesser degree blood
      pressure. Beneficial effects (need for renal replacement therapy and mortality)
      of low dose in patients at risk of, or with acute renal failure are not
      demonstrated. Dopamine has numerous potential deleterious effects on local
      circulations (pulmonary, cerebral, coronary and cutaneous), respiratory function,
      gastroduodenal motility, endocrine function (further depression of the
      hypothalamic-pituitary axis induced by stress) and immunity (partially due to
      decreased production of prolactin). Finally, in shocked adults dopamine infusion
      might be associated with an increase in mortality rate. Dopamine remains the most
      prescribed catecholamine, either in adults or children. It still is one of the
      first line drug included in the recent recommendations for the treatment of
      septic shock (norepinephrine tends to replace it), cardiogenic shock (dobutamine
      is the first drug), severe head trauma, and organ donor in cerebral death. In
      conclusion, if dopamine is today less used, there is no proof that its
      deleterious effects are associated with an excess of mortality. Thus, dopamine
      still is part of the stock of drugs that act on the cardiocirculatory system (but
      for how long?).

PMID- 17521856
TI  - [Prevention and treatment of postoperative nausea and vomiting in children. An
      evidence-based approach].
AB  - Significant improvement towards an efficacious control of postoperative nausea
      and vomiting (PONV) has taken place recently. These improvements may be
      summarised using the "rule of three". That rule describes a pragmatic and
      rational approach of PONV control. First, identify the patient at risk using
      predictive factors. Second, modify the anaesthesia technique to keep the baseline
      risk as low as possible. Third, administer antiemetics rationally, considering
      their degree of efficacy, their risk, and their potential additive effects.
      Despite considerable research efforts, identifying the patient at high risk of
      PONV remains a difficult task. However, today, we understand the degree of
      efficacy, dose-responsiveness, and adverse effects of most antiemetics. None of
      those molecules should be regarded as being universally efficacious, there is no
      gold standard, and, when used alone, their degree of efficacy is limited. Thus,
      they should be combined for improved efficacy. Among the most promising molecules
      are butyrophenones (droperidol, haloperidol), 5-HT(3) receptor antagonists
      (ondansetron, dolasetron, tropisetron, granisetron), and steroids (for instance,
      dexamethasone). The lack of relevant paediatric PONV data remains a major
      drawback and is highly unsatisfactory. Hopefully, future research will further
      improve the control of PONV not only in adults but also in children.

PMID- 17521857
TI  - [Pathophysiology and genetics of classic HFE (type 1) hemochromatosis].
AB  - Hereditary type 1 HFE hemochromatosis is associated with homozygosity for the
      p.Cys282Tyr mutation of the HFE gene (C282Y mutation). The p.Cys282Tyr mutation
      of the HFE gene leads to an abnormal reduction in hepatic expression of hepcidin,
      a protein that appears to control the release of iron from enterocytes and
      macrophages towards plasma. Abnormally low hepcidin levels promote an increase in
      the bioavailability of plasma iron, characterized by elevated transferrin
      saturation and the appearance of non transferrin bound iron. This nontransferrin
      bound iron is avidly taken up by the liver, heart, and pancreas, the principal
      target organs for systemic iron overload. The variable penetrance of this disease
      is related to environmental and genetic factors. Among the genetic factors,
      mutations of some newly identified genes may aggravate the phenotype of iron
      overload associated with homozygosity for the p.Cys282Tyr mutation of the HFE
      gene; these new genes include those of hemojuvelin (HJV), transferrin receptor 2
      (TfR2), and hepcidin (HAMP).

PMID- 17521858
TI  - [Paclitaxel-induced lupus].
AB  - INTRODUCTION: Paclitaxel (Taxol) is a drug derived from the bark of the Pacific
      yew tree and is widely used in cancer treatment, especially for breast, ovarian,
      and lung cancers. It has not previously been reported to induce lupus. CASE: We
      report the case of a woman with ovarian cancer who developed paclitaxel-induced
      lupus on two occasions. Both times, the paclitaxel dramatically improved the
      ovarian cancer. DISCUSSION: The diagnosis of lupus was confirmed by the initial
      skin appearance, elevated levels of antinuclear antibodies, recurrence on
      reintroduction, and biopsy results. To our knowledge, it is the first case
      reported of paclitaxel-induced lupus.

PMID- 17521859
TI  - [New legislation about clinical research involving "usual care": reminder of
      recent problems].
AB  - OBJECTIVE: The regulatory framework of clinical research in France was recently
      modified substantially, in part to transpose into French law directive 2001/20/EC
      of the European Parliament and Council, which concerns only drug trials. The
      revision also covered research on "human beings" (Public Health L. 2004-806, 2006
      450), on biological samples (revision of bioethics, L. 2004-800) and on data (the
      so-called CNIL act, L. 2004-801). The value of this set of texts (statutes,
      decrees, and regulations) is that it diversifies and clarifies the different
      forms of clinical research. METHODS: This article describes the painful
      progression of important public health studies, most often with "academic"
      sponsors. RESULTS: The 5 studies described here managed to overcome a variety of
      obstacles posed by the pre-2004 regulations. COMMENTS: To understand the new
      provisions, it is useful to recall the difficulties, imprecision and inaptness of
      the earlier regulations.

PMID- 17521860
TI  - Monoclonal antibodies recognizing the Enterococcus faecalis collagen-binding
      MSCRAMM Ace: conditional expression and binding analysis.
AB  - Enterococci are opportunistic pathogens known to cause numerous clinical
      infections and complications in humans. Adhesin-mediated binding to extracellular
      matrix (ECM) proteins of the host is thought to be a crucial step in the
      pathogenesis of these bacterial infections. Adhesin of collagen from Enterococcus
      faecalis (Ace) is a cell-wall anchored protein of E. faecalis that has been shown
      to be important for bacterial binding to the ECM. In this report, we characterize
      the conditions for Ace expression and demonstrate Ace binding to mammalian
      epithelial and endothelial cells as well as to collagens found in the ECM. To
      further characterize Ace expression and function, we report the generation of a
      panel of monoclonal antibodies (mAbs) directed against this important E. faecalis
      virulence factor. Through the use of multiple in vitro assays, surface plasmon
      resonance and flow cytometry, we have characterized this panel of mAbs which may
      prove to be not only beneficial in studies that address the precise biological
      role of adhesion of E. faecalis, but may also serve as beneficial therapeutic
      agents against E. faecalis infections.

PMID- 17521862
TI  - Determination of major human cytochrome P450s activities in 96-well plates using
      liquid chromatography tandem mass spectrometry.
AB  - At the early stage of drug discovery, thousands of new chemical entities (NCEs)
      may be screened before a single candidate can be identified for development.
      Evaluation of the effect of NCEs on human CYP450 enzyme activities is a key issue
      in pharmaceutical development as it may explain inter-subject variability, drug
      drug interactions, non-linear pharmacokinetics and toxic effects. A liquid
      chromatography tandem mass spectrometry (HPLC-MS/MS) method has been developed
      for the fast and routine analysis of major human CYP450s enzyme activities
      (CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) in primary
      hepatocyte cell cultures. The high sensitivity and selectivity of mass
      spectrometry has allowed traditional assays to be minimized, thus enabling the
      use of 96-well plate format which markedly reduced the number of hepatocytes
      needed for each cytochrome CYP450 activity measurement, a fact that is
      particularly critical concerning human hepatocytes.

PMID- 17521863
TI  - Cytotoxicity of peroxisome proliferator-activated receptor alpha and gamma
      agonists in renal proximal tubular cell lines.
AB  - Fibrates and thiazolidinediones are agonists of peroxisome proliferator-activated
      receptors (PPAR) alpha and gamma, pharmacologically designed to control
      dyslipidemia and insulin resistance, respectively. Several works have reported
      the toxicity of some agonists in a number of tissues. In this work we have
      analyzed the toxicity of two PPARalpha (WY14643 and clofibrate) and two PPARgamma
      (pioglitazone and ciglitazone) agonists, using three different renal proximal
      tubular cell lines: Opossum OK, pig LLC-PK1, and murine MCT. Cell death was
      determined by the activity of intracellular lactate dehydrogenase. WY14643 and
      ciglitazone increased cell death with LC50 values of 92-124 microM and 8.6-14.8
      microM, respectively, depending on the cell line. Clofibrate and pioglitazone
      were, however, non-cytotoxic even at concentrations of 10 and 100 higher than the
      corresponding EC50, which suggests that cell death is independent of PPAR
      activation. Discrimination between apoptosis or necrosis was analyzed by light
      microscopy and stress fiber morphology, double staining with acridine orange and
      ethidium bromide, binding of annexin V, caspase-3 activity, and DNA laddering.
      With these methods, no signs of apoptosis were observed, which suggests a direct
      necrosis of the compounds on these renal proximal tubular cell lines.

PMID- 17521864
TI  - Induction of EROD activity by 1-phenylimidazole and beta-naphthoflavone in
      rainbow trout cultured hepatocytes: a comparative study.
AB  - The classical pathway for induction of cytochrome P4501A (CYP1A) by xenobiotics
      is ligand binding to the aryl hydrocarbon receptor (AhR). However, several
      studies with mammalian cell systems point out a range of xenobiotics including
      imidazole derivatives, which are able to activate CYP1A through non-classical
      mechanisms. The objective of the present work is to compare induction of CYP1A
      (determined at the catalytic level as 7-ethoxyresorufin-O-deethylase, EROD) in
      rainbow trout (Oncorhynchus mykiss) hepatocytes by the prototypic AhR ligand,
      beta-naphthoflavone (betaNF), and by the imidazole derivative, 1-phenylimidazole
      (PIM). PIM was able to induce EROD activity although its potency was clearly
      lower than that of betaNF. In order to assess the relative importance of
      classical AhR ligand binding and alternative signaling pathways in CYP1A
      induction by PIM, co-exposure experiments with the partial AhR antagonist alpha
      naphthoflavone (alphaNF) or with inhibitors of protein kinase C (staurosporine)
      and tyrosine kinases (genistein, herbimicine) were performed. alphaNF and
      herbimicin provoked a decrease of EROD induction both by betaNF and PIM, whereas
      staurosporine and genistein remained without effect. The overall similarities in
      the response of betaNF and PIM to the various inhibitors suggest that both
      compounds, in apparent contrast to the behaviour of some other imidazole
      derivatives, induce CYP1A following similar mechanisms.

PMID- 17521865
TI  - The relation of depression and anxiety to measures of executive functioning in a
      mixed psychiatric sample.
AB  - The relationship between mood and executive functioning is of particular
      importance to neuropsychologists working with mixed psychiatric samples. The
      present study evaluated the relation of self-reported depression and anxiety to
      several common measures of executive functioning: the Wisconsin Card Sorting
      Test, the Trail Making Test, the Controlled Oral Word Association, and the Letter
      Number Sequencing subtest of the Weschler Adult Intelligence Scale-III. Records
      from 86 adult patients evaluated in an outpatient psychiatry unit were examined.
      Correlations between self-reported depression or anxiety and most measures of
      executive functioning were small and non-significant. The variance predicted by
      depression or anxiety after controlling for age, gender, and IQ was minimal
      (typically < or =3.0%), even after conducting diagnostic subgroup analyses. These
      results suggest that impaired performance on measures of executive functioning is
      minimally related to self-reported depression and anxiety within mixed
      psychiatric settings.

PMID- 17521866
TI  - Neuropsychological exploration of alleged mold neurotoxicity.
AB  - Cognitive and emotional correlates of toxic mold exposure and potential dose
      response effects for both outcomes were investigated. Self-reported length of
      exposure, time since last exposure, and serum immunoglobulin (IgG) levels were
      assessed. Despite CNS complaints often seen with mold exposed individuals,
      overall results did not uncover concomitant cognitive deficits suggested in
      previous studies or a significant reduction in intellectual functioning. Fewer
      subjects were excluded as result of failing effort/motivation assessment than
      expected. Correlations of IgG and cognitive function are discussed. A dose-effect
      for self-reported length of exposure and cognitive outcome was not seen. The
      sample's overall Minnesota Multiphasic Personality Inventory II (MMPI-2) profile
      indicated elevations on scales 1, 2, 3, 7 and 8. MMPI-2 clinical scales 1 and 3
      were significantly correlated with length of exposure. The MMPI-2 may be
      sensitive to increasing physical and emotional sequelae as length of exposure
      increases. A potential subgroup of cognitively impaired outliers within mold
      exposure litigants is explored. Limitations of self-reported and objective
      measurements for mold exposure and exploratory statistical methodology are
      discussed.

PMID- 17521867
TI  - The Three Words-Three Shapes test: normative data for the Turkish elderly.
AB  - The Three Words-Three Shapes (3W3S) test is a measure of verbal and nonverbal
      material in the same modality. It was originally designed as an easy bedside test
      for elderly patients to measure learning, memory, recall and recognition. This
      paper is based on a study that has adapted a shorter version of that test to the
      Turkish language and produced a set of normative data derived from a sample of
      236 healthy adults (age 50-100). The purpose of the study was to investigate the
      influence of age, gender and education on the participants' performances on 3W3S.
      According to linear regression results, both education and age explained
      significant and sizable portions of variances on most of the 3W3S subscale test
      scores.

PMID- 17521868
TI  - The child behavior checklist broad-band scales predict subsequent
      psychopathology: A 5-year follow-up.
AB  - OBJECTIVE: To evaluate the utility of the Child Behavior Check list (CBCL) for
      identifying children of parents with panic disorder or major depression at high
      risk for future psychopathology. METHODS: Baseline Internalizing and
      Externalizing CBCL T-scores were used to predict subsequent depressive, anxiety,
      and disruptive behavior disorders at a 5-year follow-up in children of parents
      with panic disorder, major depression, or neither disorder. RESULTS: The
      Internalizing scale predicted subsequent agoraphobia, generalized anxiety
      disorder, separation anxiety disorder, and social phobia. In contrast, the
      Externalizing scale predicted subsequent disruptive behavior disorders and major
      depression. CONCLUSIONS: The convergence of these results with previous findings
      based on structured diagnostic interviews suggests that the CBCL broad-band
      scales can inexpensively and efficiently help identify children at high risk for
      future psychopathology within a population of children already at risk by virtue
      of parental psychopathology.

PMID- 17521869
TI  - Computational and biological inference of gene regulatory networks of the LINE-1
      retrotransposon.
AB  - Computational approaches were used to define structural and functional
      determinants of a putative genetic regulatory network of murine LINE-1 (long
      interspersed nuclear element-1), an active mammalian retrotransposon that uses
      RNA intermediates to populate new sites throughout the genome. Polymerase (RNA)
      II polypeptide E AI845735 and mouse DNA homologous to Drosophila per fragment
      M12039 were identified as primary attractors. siRNA knockdown of the aryl
      hydrocarbon receptor NM_013464 modulated gene expression within the network,
      including LINE-1, Sgpl1, Sdcbp, and Mgst1. Genes within the network did not
      exhibit physical proximity and instead were dispersed throughout the genome. The
      potential impact of individual members of the network on the global dynamical
      behavior of LINE-1 was examined from a theoretical and empirical framework.

PMID- 17521870
TI  - A substitution mutation in the myosin binding protein C gene in ragdoll
      hypertrophic cardiomyopathy.
AB  - Familial hypertrophic cardiomyopathy (HCM) is a primary myocardial disease with a
      prevalence of 1 in 500 in human beings. Causative mutations have been identified
      in several sarcomeric genes, including the cardiac myosin binding protein C
      (MYBPC3) gene. Heritable HCM also exists in a large-animal model, the cat, and we
      have previously reported a mutation in the MYBPC3 gene in the Maine coon breed.
      We now report a separate mutation in the MYBPC3 gene in ragdoll cats with HCM.
      The mutation changes a conserved arginine to tryptophan and appears to alter the
      protein structure. The ragdoll is not related to the Maine coon and the mutation
      identified is in a domain different from that of the previously identified feline
      mutation. The identification of two separate mutations within this gene in
      unrelated breeds suggests that these mutations occurred independently rather than
      being passed on from a common founder.

PMID- 17521871
TI  - One year pre-post intervention follow-up of psychological, immune, endocrine and
      blood pressure outcomes of mindfulness-based stress reduction (MBSR) in breast
      and prostate cancer outpatients.
AB  - OBJECTIVES: This study investigated the ongoing effects of participation in a
      mindfulness-based stress reduction (MBSR) program on quality of life (QL),
      symptoms of stress, mood and endocrine, immune and autonomic parameters in early
      stage breast and prostate cancer patients. METHODS: Forty-nine patients with
      breast cancer and 10 with prostate cancer enrolled in an eight-week MBSR program
      that incorporated relaxation, meditation, gentle yoga and daily home practice.
      Demographic and health behaviors, QL, mood, stress symptoms, salivary cortisol
      levels, immune cell counts, intracellular cytokine production, blood pressure
      (BP) and heart rate (HR) were assessed pre- and post-intervention, and at 6- and
      12-month follow-up. RESULTS: Fifty-nine, 51, 47 and 41 patients were assessed pre
      and post-intervention and at 6- and 12-month follow-up, respectively, although
      not all participants provided data on all outcomes at each time point. Linear
      mixed modeling showed significant improvements in overall symptoms of stress
      which were maintained over the follow-up period. Cortisol levels decreased
      systematically over the course of the follow-up. Immune patterns over the year
      supported a continued reduction in Th1 (pro-inflammatory) cytokines. Systolic
      blood pressure (SBP) decreased from pre- to post-intervention and HR was
      positively associated with self-reported symptoms of stress. CONCLUSIONS: MBSR
      program participation was associated with enhanced quality of life and decreased
      stress symptoms, altered cortisol and immune patterns consistent with less stress
      and mood disturbance, and decreased blood pressure. These pilot data represent a
      preliminary investigation of the longer-term relationships between MBSR program
      participation and a range of potentially important biomarkers.

PMID- 17521872
TI  - Impact of an absorbent silver-eluting dressing system on lower extremity
      revascularization wound complications.
AB  - Surgical wounds for lower extremity revascularization are prone to infection and
      dehiscence. Acticoat Absorbent, an antimicrobial dressing, offers sustained
      release of ionic silver. We hypothesized that immediate application of Acticoat
      as a postoperative dressing would reduce wound complications in patients
      undergoing leg revascularization. All infrainguinal revascularization cases
      involving leg incisions at a single Veterans Administration Medical Center were
      identified from July 1, 2002, to September 30, 2005. The control group received
      conventional dressings, while the treatment group received an Acticoat dressing.
      Wound complication rates were captured via National Surgical Quality Improvement
      Program data. Patient characteristics and procedure distributions were similar
      between groups. The wound complication rate fell 64% with utilization of the
      Acticoat-based dressing (control 14% [17/118], treatment 5% [7/130]; P = 0.016).
      An Acticoat-based dressing system offers a potentially useful, cost-effective
      adjunct to reduce open surgical leg revascularization wound complications.

PMID- 17521873
TI  - Decrease of mortality of ruptured abdominal aortic aneurysm after centralization
      and in-hospital quality improvement of vascular service.
AB  - Our aim was to determine whether organizational changes could improve the outcome
      after ruptured abdominal aortic aneurysm (RAAA). Regional centralization and
      quality improvement in the in-hospital chain of treatment of RAAA included
      strengthening of the emergency preparedness and better availability of
      postoperative intensive care. During the reorganization, all patients with RAAA
      were admitted to Helsinki University Central Hospital (HUCH) from Helsinki and
      Uusimaa district. RAAA patients in the hospital district of Helsinki and Uusimaa
      between 1996 and 2004 were identified. The study period was divided into three
      periods: I, control; II, change; and III, present. Of the total of 626 patients
      with RAAA, 352 (56%) were admitted to the HUCH, of whom 315 (90%) underwent
      surgery. During the study period, population-based mortality decreased from 77%
      to 56% (P < 0.001) and 90-day mortality, from 54% to 28% (P = 0.002). Operative
      30-day mortality was 19% during the third period and lower than previously (P =
      0.001). Our results seem to argue in favor of centralization of emergency
      vascular services with adequate manpower and operative expertise in the first
      line and with availability of closed-unit postoperative critical care to achieve
      better results as these measures were associated with a positive impact on
      survival.

PMID- 17521874
TI  - S-100B release during carotid endarterectomy under local anesthesia.
AB  - The neuronal protein S-100B has been found to be an indicator of cellular brain
      damage. The aim of the study was to evaluate whether cross-clamping of the
      carotid artery for carotid endarterectomy (CEA) under local anesthesia is
      associated with the same S-100B release pattern as during general anesthesia,
      where an increase in S-100B concentration in the jugular vein blood of 120% has
      been reported. In 45 consecutive patients undergoing CEA under local anesthesia,
      serum S-100B samples were drawn before surgery (T1), before carotid cross
      clamping (T2), before cerebral reperfusion (T3), after reperfusion but before the
      end of surgery (T4), and 6 hr postoperatively (T5). At T1 and T5, blood samples
      were drawn only from the radial artery. Intraoperatively (T2-T4), samples were
      collected from the internal jugular vein additionally. S-100B levels were
      determined using an immunoluminometric assay (LIAISON) Sangtec 100; Sangtec,
      Bromma, Sweden). In eight patients, it was necessary to insert an intraluminal
      shunt because of signs of cerebral ischemia. In the remaining 37 patients, median
      carotid clamping time was 40 min. There were no neurological complications. There
      were no differences in baseline S-100B levels regarding gender and
      symptomatology. Median baseline (T1) and postoperative (T5) S-100B levels were
      identical (0.077 microg/L). All blood samples from the jugular vein showed
      significantly higher median S-100B levels than the corresponding arterial blood
      samples. Only slight increases of 13% and 18% were found during cross-clamping
      (T3) compared to the first intraoperative measurement (T2) in the venous and
      arterial samples, respectively, which was followed by decreases of 5% and 18%,
      respectively (T3-T4). S-100B release did not differ at any time point between
      patients who needed and patients who did not need a shunt, in either the arterial
      or the venous blood samples. During uncomplicated CEA under local anesthesia,
      there is no relevant increase of S-100B. These results are different from those
      reported when CEA is done under general anesthesia.

PMID- 17521875
TI  - The surgical management of aortic root vessel anomalies presenting in adults.
AB  - Anomalies of the aortic root vessels may present in adults and are common
      incidental findings during standard vascular imaging. Knowledge of their
      presentation and management is important for surgeons dealing with vascular
      pathology within these anomalous vessels. A comprehensive literature search was
      conducted and a review of the current opinion performed on the embryology,
      clinical features, and surgical treatment of aortic root vessel anomalies, with
      particular emphasis on their management in adults. A classification system for
      aortic arch anomalies based on arch configuration is presented: (1) double aortic
      arch, (2) right aortic arch, (3) left aortic arch with abnormal branching, and
      (4) interrupted aortic arch. Anomalies of the aortic root vessels may be
      classified based on their presence or absence, their anomalous size or course, or
      their atypical origin, bifurcation, or subsequent branching pattern. A
      symptomatic aberrant right subclavian artery may be encountered by vascular
      surgeons, and a right supraclavicular approach would appear the most appropriate
      method of repair. Knowledge of aortic arch and root vessel anomalies is important
      for any clinician dealing with cardiothoracic, head and neck, or intracranial
      pathology. Vascular surgeons may encounter these anomalies during routine
      practice and may need to deal with their clinical sequelae.

PMID- 17521876
TI  - Stenosis of the upper body arteries in association with coarctation and
      interrupted aortic arch.
AB  - Coarctation of the aorta and interrupted aortic arch are not usually associated
      with stenosis of the innominate, common carotid, or subclavian arteries. We
      report two patients with stenoses of combinations of these arteries, one in
      association with coarctation (stented later in life) and the other in association
      with interrupted arch (arterial stenoses surgically repaired at the time of
      surgery for the arch proper). Both have done well.

PMID- 17521877
TI  - Mid-aortic syndrome and renovascular hypertension in a 14-year-old Iraqi girl:
      pitfalls in diagnosis and surgical management.
AB  - Mid-aortic syndrome remains an uncommon cause of hypertension in the pediatric
      population. Reported management options include percutaneous intervention,
      medical management, renal autotransplantation, and bypass of diseased portions of
      the aorta with prosthetic or autologous conduits. We report a case of a 14-year
      old Iraqi female with mid-aortic syndrome, confirmed by both computed tomographic
      angiography and magnetic resonance angiography. The patient underwent a
      successful aorto-aortic, aorto-mesenteric, and aorto-birenal artery bypass with a
      polytetrafluoroethylene graft. Optimal management for this condition is surgical
      bypass.

PMID- 17521878
TI  - Model inversion by parameter fit using NN emulating the forward model: evaluation
      of indirect measurements.
AB  - The usage of inverse models to derive parameters of interest from measurements is
      widespread in science and technology. The operational usage of many inverse
      models became feasible just by emulation of the inverse model via a neural net
      (NN). This paper shows how NNs can be used to improve inversion accuracy by
      minimizing the sum of error squares. The procedure is very fast as it takes
      advantage of the Jacobian which is a byproduct of the NN calculation. An example
      from remote sensing is shown. It is also possible to take into account a non
      diagonal covariance matrix of the measurement to derive the covariance matrix of
      the retrieved parameters.

PMID- 17521879
TI  - Reducing uncertainties in neural network Jacobians and improving accuracy of
      neural network emulations with NN ensemble approaches.
AB  - A new application of the NN ensemble technique to improve the accuracy (reduce
      uncertainty) of NN emulation Jacobians is presented. It is shown that the
      introduced ensemble technique can be successfully applied to significantly reduce
      uncertainties in NN emulation Jacobians and to reach the accuracy of NN Jacobian
      calculations that is sufficient for the use in data assimilation systems. An NN
      ensemble approach is also applied to improve the accuracy of NN emulations
      themselves. Two ensembles linear (or conservative) and nonlinear (uses an
      additional averaging NN to calculate the ensemble average) were introduced and
      compared. The ensemble approaches: (a) significantly reduce the systematic and
      random error in NN emulation Jacobian, (b) significantly reduce the magnitudes of
      the extreme outliers and, (c) in general, significantly reduce the number of
      larger errors. It is also shown that the nonlinear ensemble is able to account
      for nonlinear correlations between ensemble members and to improve significantly
      the accuracy of the NN emulation as compared to the linear conservative ensemble
      in terms of systematic (bias), random, and larger errors.

PMID- 17521880
TI  - Environmentally adaptive acoustic transmission loss prediction in turbulent and
      nonturbulent atmospheres.
AB  - An environmentally adaptive system for prediction of acoustic transmission loss
      (TL) in the atmosphere is developed in this paper. This system uses several back
      propagation neural network predictors, each corresponding to a specific
      environmental condition. The outputs of the expert predictors are combined using
      a fuzzy confidence measure and a nonlinear fusion system. Using this prediction
      methodology the computational intractability of traditional acoustic model-based
      approaches is eliminated. The proposed TL prediction system is tested on two
      synthetic acoustic data sets for a wide range of geometrical, source and
      environmental conditions including both nonturbulent and turbulent atmospheres.
      Test results of the system showed root mean square (RMS) errors of 1.84 dB for
      the nonturbulent and 1.36 dB for the turbulent conditions, respectively, which
      are acceptable levels for near real-time performance. Additionally, the
      environmentally adaptive system demonstrated improved TL prediction accuracy at
      high frequencies and large values of horizontal separation between source and
      receiver.

PMID- 17521881
TI  - Evaluation of the invasion front pattern of squamous cell cervical carcinoma by
      measuring classical and discrete compactness.
AB  - The invasion front pattern of squamous cell carcinoma (SCC) is a conspicuous
      histological phenomenon, which is assessed without precise criteria. The current
      study was performed to introduce the classical (C(C)) and discrete compactness
      (C(D)) as new morphometric parameters for quantification of this pattern. A
      retrospective analysis of 76 surgically treated patients with cervical carcinoma
      was conducted and the pattern of invasion was qualitatively classified as closed,
      finger-like or diffuse, respectively, by two pathologists. After digitization of
      the histological slides with a field of view of 10.4 mm x 8.3mm, tumor areas were
      labeled and C(C) and C(D) were computed based on the drawings (binary images).
      Additionally, intraindividual variation of compactness was evaluated for 12
      selected tumors. The qualitative pattern assessment by the pathologists was
      moderately reproducible with an interobserver agreement of 72% and a kappa
      coefficient of 0.44. The values of C(C) and C(D) referring to the invasion front
      patterns assigned by both pathologists were significantly different between the
      three classified groups (p< or =0.01 and p< or =0.0001), so that, both
      theoretically and in practice, compactness regards the same morphological
      feature. In due consideration of the analysis of the area under the ROC (receiver
      operating characteristic) curves and the variation coefficient of different tumor
      regions, C(D) is more suitable for practical use than C(C). Tumors with a
      microscopic invasion into the parametria and with lymph-vascular space invasion
      were found to have a lower value of C(D), which indicates a more diffuse pattern
      of invasion (p=0.028 and p=0.033). We conclude that the discrete compactness C(D)
      is a new and reproducible parameter for a computer assisted quantification of the
      invasion front pattern and, thus, defines a further phenotypic feature of SCC of
      the uterine cervix.

PMID- 17521882
TI  - Large functional repertoire of regulatory T-cell suppressible autoimmune T cells
      in scurfy mice.
AB  - Scurfy mice which lacks functional Foxp3 transcription factor and
      CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, spontaneously develop autoimmune
      responses against skin, lung, liver and tail. However, many organs/tissues are
      spared from autoimmune attack. Here, we demonstrate that scurfy mice contain
      dormant autoimmune T cells that induced new diseases such as sialoadenitis,
      dacryoadenitis, pancreatitis, gastritis, intestinal inflammation, colitis, and
      myositis in RAG-1 KO mice. Inflammation in as many as 12 organs/tissues was
      consistently induced in individual recipients with scurfy lymph node cells
      containing as few as 1.25 x 10(6) CD4(+) T cells. Moreover, transfer of the
      multiple organ autoimmune diseases could be suppressed by as little as 0.5 x
      10(6) CD4(+)CD25(+) Treg cells, mediated by inhibiting autoimmune T-cell
      expansion. Our study provides evidence for the presence of a large repertoire of
      autoimmune lymphocytes against various organs/tissues in scurfy mice as well as
      Treg cells in B6 mice capable of suppressing the expansion of these autoimmune
      lymphocytes. Various conditions that control the expression of autoimmune T cells
      are discussed.

PMID- 17521883
TI  - Mother-child immunological interactions in early life affect long-term humoral
      autoreactivity to heat shock protein 60 at age 18 years.
AB  - The presence of anti-heat shock protein 60 (Hsp60) antibodies in healthy
      individuals and the association of these antibodies with diseases such as
      arthritis and atherosclerosis are well documented. However, there is limited
      population-level data on interindividual variation in anti-Hsp60 levels. We
      investigated the influence of early-life factors on IgG reactivity to human Hsp60
      at age 18 years. A population-based prospective birth cohort study included 5914
      births in the city of Pelotas, Brazil, in 1982. Early-life exposures were
      documented during home visits in childhood. In 2000, 79% of all males in the
      cohort were traced. Sera from a systematic 20% sample (411 subjects) were
      analyzed. Anti-Hsp60 total IgG reactivity was determined by ELISA. Data were
      analyzed using analysis of variance and generalized linear models. Anti-Hsp60
      reactivity was lognormally distributed and showed a significant direct
      correlation with low birthweight (p=0.039) and total duration of breastfeeding
      (p=0.018), of which only the latter remained significant after adjustment for
      potential confounders. Reactivity was not associated with asthma, pneumonia,
      diarrhea, or early-life malnutrition. Mother-child immunological interactions,
      rather than infection/disease factors seem to be associated with reactivity to
      Hsp60 later in life. This is in agreement with the hypothesis that maternal
      antibodies influence future antibody profile.

PMID- 17521884
TI  - Pertussis toxin promotes macrophage survival through inhibition of acid
      sphingomyelinase and activation of the phosphoinositide 3-kinase/protein kinase B
      pathway.
AB  - Apoptosis is an important mechanism involved in regulating the number of
      macrophages present at sites of inflammation. Several lines of evidence indicate
      that blocking macrophage apoptosis can increase atherosclerosis. We previously
      reported that oxidized LDL can inhibit apoptosis in cultured bone marrow-derived
      macrophages. We used pertussis toxin (PTX) to test whether G protein coupled
      receptors are activated by oxLDL. PTX is a bacterial toxin that inhibits Gi
      activation by ADP-ribosylating the alpha subunit of Gi, preventing the subunit
      from interacting with receptors. Unexpectedly, we found that PTX by itself
      selectively blocks macrophage apoptosis in a dose-dependent manner. PTX acts in
      part by inhibiting acid sphingomyelinase activity which in turn prevents
      generation of ceramide, which is required for macrophage apoptosis. A Gi
      activator peptide, mastoparan, increased ceramide levels in macrophage and
      induced apoptosis, but pre-treatment with PTX partially overrode mastoparan
      induced apoptosis. The anti-apoptotic effect of PTX was found to require ADP
      ribosylation. PTX failed to prevent A-SMase activation or apoptosis in
      macrophages lacking TLR4. The anti-apoptotic effect of PTX involved the same
      signaling pathways as those of oxidized LDL, in that both inhibited acid
      sphingomyelinase, and activated the phosphoinositide 3 kinase (PI3K)/protein
      kinase B (PKB) pathway which leads to nuclear localization of the transcription
      factor NFkappaB and up-regulation of Bcl-XL. These results indicate that Gi
      proteins, TLR4, A-SMase and the PI3K/PKB pathway are crucial components for
      regulation of macrophage apoptosis.

PMID- 17521885
TI  - The effect of platelet-rich plasma on early and late bone healing: an
      experimental study in goats.
AB  - Four round critical-size defects were made in the foreheads of 20 goats. The
      defects were filled with autogenous particulate cancellous bone, in which 1 ml of
      platelet-rich plasma (PRP) was added in two of the four defects of each goat. The
      goats were divided into four subgroups of five goats each, which were killed
      after 1, 2, 6 and 12 weeks. The results of histologic and histomorphometric
      examination showed that early and late bone healing was not enhanced when PRP was
      used.

PMID- 17521886
TI  - Carcinoid tumour metastases to the maxilla.

PMID- 17521887
TI  - Application of orthodontic mini-implants in adolescents.
AB  - The aim of this study was to determine the success rate of mini-implants in
      adolescents, and also whether a latent period is necessary and the optimum
      placement torque in an attempt to improve the success rate in adolescent
      patients. There were 57 orthodontic patients involved in the study, with ages
      ranging from 11.7 to 36.1 years, who underwent surgery to insert mini-implants
      (169 implants). When a mini-implant endured an orthodontic force applied for 6
      months or more without any mobility, it was considered a success. The success
      rate was 63.8% in the early-load group (less than 1-month latent period) of
      adolescents, 97.2% in the late-load group (3-month latent period) of adolescents
      and 91.9% in the adult group. The success rate of the early-load group of
      adolescents was significantly inferior to those of the other groups (P<0.01). In
      measurements of the placement torque in adolescents, the success rate of the 5-10
      N cm group was significantly higher than the other groups only in the maxilla of
      the early-load group. Although the optimum torque could not be defined, a latent
      period of 3 months before loading is recommended to improve the success rate of
      the mini-implant when placed in the alveolar bone in adolescent patients.

PMID- 17521888
TI  - The submental island flap in head and neck reconstruction.
AB  - The authors describe their experience with the submental island flap for the
      primary correction of head and neck deformities following oncologic surgery, over
      the past 5 years. The use of this flap is reported in 12 patients, with a mean
      age of 67 years, requiring facial or intraoral reconstruction. A brief review of
      the key points and some refinements in the operative technique are discussed. The
      reconstruction of defects with a submental island flap was successful in every
      patient. Complications encountered were one case of temporary palsy of the
      marginal mandibular branch of the facial nerve and one case of orocutaneous
      fistula. All the donor site defects were closed primarily. The submental island
      flap is an excellent choice for the reconstruction of head and neck defects
      because of its reliability, versatility, colour and texture match, and relative
      ease of application.

PMID- 17521889
TI  - The relationship of personality traits to substance abuse in patients with
      bipolar disorder.
AB  - PURPOSE: The aim of this study is to determine if personality traits contribute
      to the likelihood of substance abuse in Bipolar Disorder (BD). SUBJECTS/MATERIALS
      AND METHODS: Fifty-nine patients meeting DSM-IV criteria for BD: 20 without any
      history of Substance Related Disorder (SRD), 21 with a lifetime history of SRD
      but without current SRD, and 18 with current SRD. Patients filled out the TCI,
      the differences were analyzed by ANOVA and the likelihood was obtained by
      Multinomial Logistic Regression. RESULTS: Only Novelty Seeking (NS) is
      statistically different between the groups. Patients with BD with current SRD
      have higher rates in NS than those with past SRD, and those without a history of
      SRD. NS was confirmed as a predicting variable, both to current SRD (OR [CI
      95%]=1.039/1.351; p=0.011) and past SRD (OR [CI 95%]=1.004/1.277; p=0.042) on
      patients with BD. DISCUSSION: The results shown would appear to confirm the
      relationship of NS with the SRD, so long as there is no clear evidence that
      indicates the association of NS with BD. CONCLUSIONS: There appears a greater
      predisposition to develop SRD in those patients with a higher degree of NS. The
      use of the Cloninger's TCI could be used in BD to determine the risk of
      developing an SRD. Early detection might help improve prognosis.

PMID- 17521890
TI  - Physician observations and perceptions of positive and negative symptoms of
      schizophrenia: a multinational, cross-sectional survey.
AB  - PURPOSE: To describe physicians' observations and perceptions of patients with
      schizophrenia and to obtain information about antipsychotic prescribing
      practices. METHODS: Psychiatrists in the United States and five European
      countries (France, Germany, Italy, Spain, and the United Kingdom) who prescribed
      antipsychotics for >or=15 patients with schizophrenia within the preceding 3
      months provided data on their patients' demographic and clinical characteristics
      and their antipsychotic prescribing practices and drug attributes influencing
      treatment choice. RESULTS: Data were collected from 872 physicians on 6523
      patients (85% European, 15% US). Most patients were aged 25-44 years, 63% were
      men, and 66% were outpatients. About 50% of patients were moderately to grossly
      dysfunctional; about 50% were unemployed; 34% and 75% were taking conventional or
      atypical antipsychotics, respectively. Frequently identified positive symptoms
      included delusions (73%), disordered thought (59%), and hallucinations (59%);
      common negative symptoms included social withdrawal (54%), impoverished thought
      (39%), and blunted affect (38%). Reasons for antipsychotic selection included
      efficacy for positive (90%) or negative symptoms (62%) and tolerability (47%).
      Inadequate control was reported more frequently for negative (71-77%) than
      positive (47-60%) symptoms. Adverse events included sedation, weight gain, and
      extrapyramidal symptoms. CONCLUSIONS: In this large, multinational, cross
      sectional survey, physicians reported that positive symptoms were more common
      than negative symptoms. Treatment for positive symptoms was more successful than
      that for negative symptoms, with physicians considering treatment inadequate for
      >70% of patients with negative symptoms.

PMID- 17521891
TI  - What is the meaning of treatment resistant/refractory major depression (TRD)? A
      systematic review of current randomized trials.
AB  - OBJECTIVE: To summarize and discuss the conceptual and operational definitions of
      treatment resistant/refractory depression (TRD) by systematically reviewing
      randomized controlled trials (RCTs) on its somatic treatment. DATA SOURCES: We
      searched the MEDLINE, Cochrane Library, PsycINFO, and EMBASE for potentially
      relevant RCTs on the somatic treatment of TRD published from January 1996 to June
      2006. STUDY SELECTION: Studies were included if they: (a) enrolled patients at
      least 18 years old with a primary diagnosis of unipolar major depression
      considered resistant/refractory to treatment at baseline, (b) had a randomized
      design, (c) were published in peer-reviewed journals, and (d) were written in
      English. Trials that enrolled patients with secondary depression were excluded
      from our review. Finally, the bibliographies of relevant articles were hand
      searched for additional references. In total, 233 full electronic references were
      retrieved, from which 47 meet the inclusion criteria. DATA EXTRACTION: Through a
      standardized form, we collected data describing the diagnostic procedure, the
      terminology and definition of TRD employed, the methodology for assessing the
      adequacy of previous treatments (in terms of type of ascertainment, dose, and
      duration), and the minimum required depressive symptoms at baseline. DATA
      SYNTHESIS: Overall, RCTs diverged regarding the majority of the conceptual and
      methodological issues involved in the ascertainment of TRD. For example, eleven
      terms were used to describe resistance/refractoriness in depression, and six
      different criteria were employed to define the categorical presence of TRD
      (ranging form non-response to one antidepressant to non-response to two or more
      antidepressants from different pharmacological classes). Regarding the evaluation
      of previous treatments, the majority of RCTs did not use systematic methods to
      gather data, and diverge substantially on the minimum acceptable medication doses
      and trial durations. CONCLUSIONS: There is a clear need for an internationally
      shared framework of concepts and methods for the investigation of TRD that could
      reduce current idiosyncrasies and provide a reference system. Such a foundation
      is essential for the interpretation of research findings and for their
      translation to clinical practice.

PMID- 17521893
TI  - [Laparoscopic treatment of congenital inguinal hernias in children (212
      patients)].
AB  - OBJECTIVES: Laparoscopic treatment of inguinal hernias in children remains
      controversial. The inguinal approach is the only recommended procedure nowadays.
      The aim of our series was to precise the results of this technique and its
      advantages. POPULATION AND METHODS: We report our preliminary experience in
      laparoscopy for inguinal hernias in 212 children. RESULTS: Laparoscopy allowed us
      to discover 26 controlateral hernias not previously diagnosed, 3 direct hernias
      with 1 of them associated with a patent process vaginalis, 2 femoral hernias
      associated with a patent process vaginalis, 1 double pouch hernia and 1 volvulus
      of a cyst developed from a patent process vaginalis. In case of recurrence after
      an inguinal approach, laparoscopy seemed to be helpful to evaluate the anatomical
      lesion. We observed only 1 recurrence. DISCUSSION: Indications for laparoscopy in
      case of inguinal hernia in children are reviewed and discussed in the literature.
      Laparoscopic diagnosis for a precise diagnosis is no more discussed. Various
      techniques were proposed in case of laparoscopic treatment of inguinal hernias in
      children: most of surgeons realized only a suture of the sac. We prefer to
      dissect all the sac in order to avoid any recurrence. Advantages of laparoscopic
      approach become more obvious after the age of 2 years when the opening of the
      parietal wall is required in case of an inguinal approach and when local
      anaesthesia is no more recommended. The opportunity to diagnose a bilateral
      hernia when non diagnosed before surgery or to discover a femoral or a direct
      hernia, or in case of recurrence after an inguinal approach, the atraumatic
      dissection of the vas and spermatic vessels at the level of the internal inguinal
      ring, are the main advantages for laparoscopy.

PMID- 17521892
TI  - The COMT Val158Met polymorphism and temporal lobe morphometry in healthy adults.
AB  - We examined the relationship between COMT Val158Met genotype and temporal lobe
      volumes, including the caudate as a control region. Thirty-one healthy subjects
      completed 1.5T brain MRI and genotyping. After controlling for demographics,
      Val158 allele homozygotes exhibited significantly smaller temporal lobe and
      hippocampal volumes, with a trend for smaller amygdala volumes.

PMID- 17521894
TI  - [First-generation immigrant adolescents' physical and mental health and
      behaviors].
AB  - The objectives of this article are to: a) review literature about physical,
      mental health and behaviors of first generation immigrant adolescents and its
      evolution; b) compare first and second generations immigrant adolescents'health.
      Studies usually compare first generation and others adolescents groups: 1) first
      generation adolescents shows better physical health and behaviors than second
      generation; 2) first generation adolescents shows variable results for mental
      health compared to second generation and host adolescents according to the
      studies; 3) a degradation of physical health and behaviors is observed with the
      time passed in the host country. These results show necessity of a precocious
      evaluation of first generation adolescents' needs for a good planification of
      health promotion and prevention actions to preserve their health advantage at
      arrival.

PMID- 17521895
TI  - Preparation and characterization of radioactive dirhenium decacarbonyl-loaded
      PLLA nanoparticles for radionuclide intra-tumoral therapy.
AB  - This study describes the development of biocompatible radioactive rhenium-loaded
      nanoparticles for radionuclide anti-cancer therapy. To achieve this goal,
      dirhenium decacarbonyl [Re2(CO)10] has been encapsulated in poly(L-lactide) based
      nanoparticles by an oil-in-water emulsion-solvent evaporation method. A 3(3)
      factorial design method was applied to investigate the influence of both the
      proceeding and formulation parameters including the stirring speed and the
      concentration of both the PLLA polymer and the poly(vinyl alcohol) stabiliser on
      both nanoparticles size and the Re2(CO)10 encapsulation efficacy. The factorial
      design results attributed a clear negative effect for the stirring speed and the
      stabiliser concentration on the nanoparticles size while the polymer
      concentration exhibited a positive one. Regarding the Re2(CO)10 encapsulation
      efficacy, higher values were obtained when higher polymer concentrations, lower
      stabiliser concentrations or slower stirring speeds were applied in the
      preparation. Different tests were thereafter performed to characterize the
      Re2(CO)10-loaded nanoparticles. The nanoparticles size, being experimentally
      controlled by the above mentioned parameters, ranged between 330 and 1500 nm and
      the maximum rhenium loading was 24% by nanoparticles weight as determined by
      atomic emission assays and neutron activation analysis. Furthermore, the rhenium
      distribution within nanoparticles has been shown to be homogeneous as confirmed
      by the energy dispersive X-ray spectrometry. DSC assays demonstrated that
      Re2(CO)10 was encapsulated in its crystalline initial state. Other experiments
      including FT-IR and NMR did not show interactions between PLLA and Re2(CO)10. To
      render them radioactive, these nanoparticles have been bombarded with a neutron
      flux of 1.45x10(13) n/cm2/s during 1 h. The SEM micrographs of nanoparticles
      after neutron bombardment showed that the nanoparticles remained spherical and
      separated but slightly misshaped. These applied neutron activation conditions
      yielded a specific activity of about 32.5 GBq per gram of nanoparticles.
      Preliminary estimations allow us to think that a sole injection of 50 mg of these
      activated nanoparticles into a brain tumor model (4.2 cm diameter) would deliver
      a tumor absorbed dose of up to 47 Gy. In conclusion, these dirhenium decacarbonyl
      loaded nanoparticles represent a novel promising tool for radionuclide anti
      cancer therapy.

PMID- 17521896
TI  - Patient-perceived benefit during one year of treatment with Doloteffin.
AB  - We recruited 114 patients (56 with chronic nonspecific low back pain, 37 with
      osteoarthritic knee and 21 with osteoarthritic hip pain) into a surveillance of
      the effects of taking Doloteffin at a dose providing 60 mg harpagoside per day
      for up to 54 weeks. Their symptoms and well-being were monitored at 4-6 week
      intervals by disease-specific and generic outcome measures, and the patients also
      kept a diary of their pain and requirement for rescue medication. The principal
      analyses were on the basis of Intention to Treat (ITT) with Last Value Carried
      Forward (LOCF). A Multivariate Analysis of Variance (MANOVA) indicated an
      appreciable overall improvement during the surveillance, similar in the Back,
      Knee and Hip groups. In separate ANOVAs, most of the individual outcome scores
      decreased significantly over time. Multiple regression analyses indicated that
      changes from baseline were independent of patients' characteristics. Additional
      analgesic requirements (which were very modest) declined during the year of
      surveillance. "Response during treatment", assessed according to criteria adapted
      from joint proposals of the Outcome Measures in Rheumatoid Arthritis Clinical
      Trials group and the Osteoarthritis Research Society International group, was
      achieved in 75% of patients, and was reflected in the percentages who rated the
      treatment as "good" or "very good". Adverse events were few and none were
      serious.

PMID- 17521897
TI  - Reduced supportive capacity of bone marrow stroma upon chemotherapy is mediated
      via changes in glycosaminoglycan profile.
AB  - High dose chemotherapy and radiation have been found to impair the hematopoiesis
      supportive capacity of bone marrow stroma. We now provide evidence for an
      important role of chemotherapy-induced alterations in stromal glycosaminoglycans
      (GAGs) in reduction of the supportive properties of stromal fibroblasts. Exposure
      to cytarabine resulted in a pronounced increase in hyaluronan, both in the
      cell/matrix (p<0.03) and supernatant fraction (p<0.05). Gene expression analysis
      showed a corresponding increase in gene expression of hyaluronan synthase 1,
      indicating that the increase in hyaluronan is at least partly under genetic
      control. Functionally, hyaluronan significantly inhibited the proliferation of
      early megakaryocytic progenitor cells in a dose dependent way (p=0.01). The
      increase in hyaluronan was confirmed in vivo by showing a >2-fold increase in
      bone marrow hyaluronan of patients after chemo- and/or radiotherapy as
      conditioning for an allogeneic stem cell transplantation, indicating
      physiologically relevance. Furthermore, there was a trend towards a decrease in
      the amount and sulfation of stromal heparan sulfate proteoglycans upon exposure
      to cytarabine, resulting in a 40% reduced binding of SDF1-alpha to stromal cells
      (p<0.05). In conclusion, there is a pronounced effect of cytarabine treatment on
      the expression of genes involved in GAG synthesis and degradation, affecting the
      synthesis and function of stromal GAGs. Our results indicate that chemotherapy
      induced changes in stromal GAG profile are likely to affect normal hematopoiesis.

PMID- 17521898
TI  - Environmentally friendly use of non-coal ashes in Sweden.
AB  - The Swedish Thermal Engineering Research Institute (Varmeforsk) initiated an
      applied research program "Environmentally friendly use of non-coal ashes", in
      2002. The program aims at increasing knowledge on the by-products of energy
      production and their application. The goal of formulating technical and
      environmental guidelines and assessments is a major point of the program, which
      is supported by about forty authorities and private organisations. The programme
      has been divided into four areas: recycling of ashes to forests, geotechnical
      applications, use in landfilling, and environmental aspects and chemistry. Among
      all results obtained, the following progress is shown: *Evidence for the positive
      effects of spreading ashes on forest growth. *A proposal for environmental
      guidelines on the utilisation of ashes in construction. *A handbook for using non
      coal fly ashes in unpaved roads. *Technical and environmental assessments of MSWI
      bottom ashes in road construction. *Development of the use of ashes with
      municipal wastewater sludge as a cover for landfills and mine tailings. *Use of
      ashes from bio-fuels in concrete and replacement of cement in stoop mining. *A
      method to classify those by-products from combustion that have mirror entries in
      the EWC as a hazardous or non-hazardous compound. The Ash Programme has also made
      it possible to increase knowledge on ashes as valuable materials, on quality
      assurance and on markets for recovered materials.

PMID- 17521899
TI  - Mathematical modeling of biomass fuels formation process.
AB  - The increasing demand for thermal and electric energy in many branches of
      industry and municipal management accounts for a drastic diminishing of natural
      resources (fossil fuels). Meanwhile, in numerous technical processes, a huge mass
      of wastes is produced. A segregated and converted combustible fraction of the
      wastes, with relatively high calorific value, may be used as a component of
      formed fuels. The utilization of the formed fuel components from segregated
      groups of waste in associated processes of co-combustion with conventional fuels
      causes significant savings resulting from partial replacement of fossil fuels,
      and reduction of environmental pollution resulting directly from the limitation
      of waste migration to the environment (soil, atmospheric air, surface and
      underground water). The realization of technological processes with the
      utilization of formed fuel in associated thermal systems should be qualified by
      technical criteria, which means that elementary processes as well as factors of
      sustainable development, from a global viewpoint, must not be disturbed. The
      utilization of post-process waste should be preceded by detailed technical,
      ecological and economic analyses. In order to optimize the mixing process of fuel
      components, a mathematical model of the forming process was created. The model is
      defined as a group of data structures which uniquely identify a real process and
      conversion of this data in algorithms based on a problem of linear programming.
      The paper also presents the optimization of parameters in the process of forming
      fuels using a modified simplex algorithm with a polynomial worktime. This model
      is a datum-point in the numerical modeling of real processes, allowing a precise
      determination of the optimal elementary composition of formed fuels components,
      with assumed constraints and decision variables of the task.

PMID- 17521900
TI  - Modeling hydrology and reactive transport in roads: the effect of cracks, the
      edge, and contaminant properties.
AB  - The goal of this research was to provide a tool for regulators to evaluate the
      groundwater contamination from the use of virgin and secondary materials in road
      construction. A finite element model, HYDRUS2D, was used to evaluate generic
      scenarios for secondary material use in base layers. Use of generic model results
      for particular applications was demonstrated through a steel slag example. The
      hydrology and reactive transport of contaminants were modeled in a two
      dimensional cross section of a road. Model simulations showed that in an intact
      pavement, lateral velocities from the edge towards the centerline may transport
      contaminants in the base layer. The dominant transport mechanisms are advection
      closer to the edge and diffusion closer to the centerline. A shoulder joint in
      the pavement allows 0.03 to 0.45 m(3)/day of infiltration per meter of joint
      length as a function of the base and subgrade hydrology and the rain intensity.
      Scenario simulations showed that salts in the base layer of pavements are
      depleted by 99% in the first 20 years, whereas the metals may not reach the
      groundwater in 20 years at any significant concentrations if the pavement is
      built on adsorbing soils.

PMID- 17521901
TI  - Biomaterial culture conditions impacting the performance of a PAM fluorometry
      based aquatic phytotoxicity assay.
AB  - An aquatic phytotoxicity assay, based on the principles of pulse amplitude
      modulated (PAM) fluorometry has recently been developed and validated under
      laboratory conditions. Characteristics of the assay include the use of
      photosynthesising biomaterial, most frequently whole organism microalgae. The
      instrument employs light probing measurements to monitor chlorophyll fluorescence
      signals emitted by the biomaterial component. These characteristics could leave
      assay performance susceptible to interference by minor variations in biomaterial
      treatment and culture conditions prior to testing. This study investigates assay
      performance in response to variations in two microalgae culture parameters; short
      term light history (24h) prior to testing and the sterility of long-term culture
      conditions. Light history of the four microalgal species tested significantly
      impacted their toxicity response, as measured with the assay. Light treatments of
      5 micromol photons m(-2)s(-1) produced the highest photosystem II quantum yields
      (Phi(II)) whilst higher light intensities resulted in an inverse relationship
      between Phi(II) and the measured toxicity response (inhibition (%) of
      photochemistry). Of the two microalgal cultures tested, sterility of culture
      conditions significantly impacted the performance of the green freshwater algae,
      Chlorella vulgaris as assay biomaterial. On average 1 microg L(-1) diuron
      inhibited photochemistry 2.6% less in axenically cultured C. vulgaris compared
      with non-axenically maintained cultures. This investigation series contributes
      valuable quality assurance data towards microalgal based PAM fluorometry assays
      and emphasises the importance of such investigations if new biorecognition
      systems are to be accredited and/or routinely incorporated for biomonitoring
      purposes.

PMID- 17521902
TI  - Oriented immobilisation of anti-pneumolysin Fab through a histidine tag for
      electrochemical immunosensors.
AB  - Orientation of reagents is a key step in the construction of immunosensors. When
      the immunoreagent is a recombinant protein, this can be achieved by employing
      hexahistidine tags. The orientation of recombinant histidine-tagged Fab fragments
      of monoclonal anti-pneumolysin antibodies on gold films is evaluated. Using
      histidine as a chelator of Ni or employing an anti-polyhistidine antibody for
      capturing the His6 residue is considered. Measurements are based in the signal of
      indigo, which comes from the hydrolysis of 3-indoxylphosphate by alkaline
      phosphatase (AP). The attachment of the enzyme occurs through the interaction of
      biotin with AP-labelled streptavidin or employing AP-conjugated immunoreagents.
      In the case of the interaction Ni-histidine, for the study of the self-assembling
      process a His-tagged and biotinylated protein (His6-GST-B) was employed. General
      conditions were studied and non-specific adsorption was avoided with the use of 1
      hexanethiol. Improvements of the signal compared with the direct adsorption were
      only achieved by the use of histidine capturing antibodies. With an optimised
      ratio anti-polyhis:His6-Fab the signal increases approximately a 100%. Precision
      is adequate and the response is linear with the concentration of pneumolysin
      between 0.1 and 10 ng/mL.

PMID- 17521903
TI  - Labor analgesia and breast feeding: avoid parenteral narcotics and provide
      lactation support.

PMID- 17521904
TI  - Assessing quality of life in patients with colorectal cancer: an update of the
      EORTC quality of life questionnaire.
AB  - The European Organisation for Research and Treatment of Cancer (EORTC) has a
      portfolio of questionnaire modules to supplement the QLQ-C30 to assess patient
      reported outcomes in cancer clinical trials. This study updated the module for
      colorectal cancer. A review of the literature identified 20 articles that used
      the EORTC colorectal module. Eight papers did not report data from scales
      addressing sexual function and 8 added additional scales to assess ano-rectal
      function. Interviews with patients (n=79) and professionals (n=11) informed item
      selection, reduction and modification. A new 29 item module was devised and
      further patient interviews (n=120) examined its format and content validity.
      Patients found the new module acceptable with relevant content. The new module,
      the EORTC QLQ-CR29, is hypothesised as containing 6 scales and 11 single items.
      An international study examining its clinical and psychometric validity will be
      performed.

PMID- 17521905
TI  - Endoluminal insertion of colonic stents.
AB  - For patients with obstructing colonic tumours endoluminal stents provide an
      alternative to surgical decompression. Used either as permanent palliation, or as
      a bridge to surgery, colonic stents have been shown to be effective, safe, and
      cost effective.

PMID- 17521906
TI  - Chemotherapy in metastatic colorectal cancer.
AB  - This article aims to provide the reader with a broad overview of the current
      chemotherapeutic options available for the treatment of patients with metastatic
      colorectal cancer. The review includes discussion of both well established and
      experimental therapies.

PMID- 17521907
TI  - 2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor
      agonists. Part 1: discovery of CB2 receptor selective compounds.
AB  - 2-Arylimino-5,6-dihydro-4H-1,3-thiazines have been identified as a novel class of
      cannabinoid agonists. A lead structure with moderate activity was discovered
      through a high throughput screening assay. Structure-activity relationships led
      to the discovery of potent agonists of CB(2) receptor. The most potent compound
      13 displays K(i) values of >5000 and 9 nM to CB(1) and CB(2) receptors,
      respectively.

PMID- 17521908
TI  - Identification of 2-(4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-3-yl)-ethylamine
      derivatives as novel GnRH receptor antagonists.
AB  - A novel series of 2-(4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-3-yl)-ethylamine
      derivatives were designed and synthesized as GnRH receptor antagonists. SAR
      studies led to a series of highly active molecules against both the rat and human
      receptors. Furthermore, one potent compound, 17j, demonstrated dose-dependent LH
      suppression in castrated rats.

PMID- 17521909
TI  - Human and rat monoamine oxidase-A are differentially inhibited by (S)-4
      alkylthioamphetamine derivatives: insights from molecular modeling studies.
AB  - Four enantiomerically pure (S)-4-alkylthioamphetamine derivatives were evaluated
      as monoamine oxidase (MAO) inhibitors using the human and rat isoforms of the
      enzyme. Molecular dockings were performed in order to gain insights regarding the
      binding mode of these inhibitors. All compounds were potent and selective MAO-A
      inhibitors although different rank orders of potencies were observed against the
      enzymes from different species. This behavior can be rationalized on the basis of
      different binding modes to each enzyme, as determined in silico. These findings
      further support the concept that MAO inhibitory activity of novel compounds,
      determined with enzymes from diverse mammalian species, should be considered with
      caution if human MAO is the final target to be addressed.

PMID- 17521910
TI  - Mechanism of the melanogenesis stimulation activity of (-)-cubebin in murine B16
      melanoma cells.
AB  - (-)-Cubebin showed a melanogenesis stimulation activity in a concentration
      dependent manner in murine B16 melanoma cells without any significant effects on
      cell proliferation. Tyrosinase activity was increased at 24-72 h after addition
      of cubebin to B16 cells, and then intracellular melanin amount was increased at
      48-96 h after the treatment. The expression levels of tyrosinase were time
      dependently enhanced after the treatment with cubebin. At the same time, the
      expression levels of tyrosinase mRNA were also increased after addition of
      cubebin. Furthermore Western blot analysis revealed that cubebin elevated the
      level of phosphorylation of p38 mitogen-activated protein kinase (MAPK).
      SB203580, a selective inhibitor of p38 MAPK, completely blocked cubebin-induced
      expression of tyrosinase mRNA in B16 cells. These results suggested that cubebin
      increased melanogenesis in B16 cells through the enhancement of tyrosinase
      expression mediated by activation of p38 MAPK.

PMID- 17521911
TI  - Synthesis and HCV inhibitory properties of 9-deaza- and 7,9-dideaza-7-oxa-2'-C
      methyladenosine.
AB  - As a part of an ongoing medicinal chemistry effort to identify inhibitors of the
      Hepatitis C Virus RNA replication, we report here the synthesis and biological
      evaluation of 9-deaza- and 7,9-dideaza-7-oxa-2'-C-methyladenosine. The parent 2'
      C-methyladenosine shows excellent intracellular inhibitory activity but poor
      pharmacokinetic profile. Replacement of the nucleoside-defining 9-N of 2'-C
      methyladenosine with a carbon atom was designed to yield metabolically more
      stable C-nucleosides. Modifications at position 7 were designed to exploit the
      importance of the hydrogen bond accepting properties of this heteroatom in
      modulating the adenosine deaminase (ADA) mediated 6-N deamination. 7-Oxa-7,9
      dideaza-2'-C-methyladenosine was found to be a moderately active inhibitor of
      intracellular HCV RNA replication, whereas 9-deaza- 2'-C-methyladenosine showed
      only weak activity despite excellent overlap of both of the synthesized target
      compounds with 2'-C-methyladenosine's three dimensional structure. Position 7 of
      the nucleobase proved to be an effective handle for modulating ADA-mediated
      degradation, with the rate of degradation correlating with the hydrogen-bonding
      properties at this position.

PMID- 17521912
TI  - The biology and chemistry of hyperlipidemia.
AB  - Coronary arterial diseases are responsible for more deaths than all other
      associated causes combined. Elevated serum cholesterol levels leading to
      atherosclerosis can cause coronary heart disease (CHD). Reduction in serum
      cholesterol levels reduces the risk for CHD, substantially. Medicinal chemists
      all around the world have been designing, synthesizing, and evaluating a variety
      of new bioactive molecules for lowering lipid levels. This review summarizes the
      disorders associated with elevation of lipids in blood and the current strategies
      to control them. The emphasis has been laid in particular on the new potential
      biological targets and the possible treatments as well as the current ongoing
      research status in the field of lipid lowering agents.

PMID- 17521913
TI  - A fluorescence probe for assaying micro RNA maturation.
AB  - A class of small RNAs known as micro-RNAs (miRNAs) has been shown to play an
      important role in development and cellular regulation in eukaryotes. Recent
      evidence also associates aberrant expression of various miRNAs with multiple
      diseases in humans including many types of cancer. An up- or downregulation of
      certain miRNAs may play a significant role in the course of these diseases. We
      were interested in whether binding of small molecules to the inactive miRNA
      precursors would block their cleavage into the active miRNAs by the enzyme Dicer.
      The inhibition of miRNA maturation might provide a new rationale for future
      therapeutic strategies. We have developed a fluorescence beacon with which to
      study the maturation of miRNAs. Details are provided of a homogeneous assay for
      detecting potential inhibitors of miRNA maturation in a high-throughput format.

PMID- 17521914
TI  - Quantitation of rabbit cytokine mRNA by real-time RT-PCR.
AB  - Fundamental understanding of rabbit immunology and the use of the rabbit as a
      disease model have long been hindered by the lack of immunological assays
      specific to this species. In the present study, we sought to develop a method to
      quantitate cytokine expression in rabbit cells and tissues. We report the
      development of a quantitative real-time RT-PCR method for measuring the relative
      levels of rabbit IFN-gamma, IL-2, IL-4, IL-10 and TNF-alpha mRNA. Quantitation
      was accomplished by comparison to a standard curve generated using plasmid DNA
      containing partial sequences of the relevant cytokines. Experimental studies
      demonstrate applicability of this assay to quantitate cytokine mRNA levels from
      rabbit spleen cells following mitogen stimulation. We have further utilized this
      assay to also examine cytokine expression in rabbit tissues during experimental
      syphilis infection.

PMID- 17521916
TI  - Folding and unfolding of helix-turn-helix motifs in the gas phase.
AB  - Ion mobility measurements and molecular dynamic simulations have been performed
      for a series of peptides designed to have helix-turn-helix motifs. For peptides
      with two helical sections linked by a short loop region:
      AcA(14)KG(3)A(14)K+2H(+), AcA(14)KG(5)A(14)K+2H(+), AcA(14)KG(7)A(14)K+2H(+), and
      AcA(14)KSar(3)A(14)K+2H(+) (Ac = acetyl, A = alanine, G = glycine, Sar =
      sarcosine and K = lysine); a coiled-coil geometry with two anti-parallel helices
      is the lowest energy conformation. The helices uncouple and the coiled-coil
      unfolds as the temperature is raised. Equilibrium constants determined as a
      function of temperature yield enthalpy and entropy changes for the unfolding of
      the coiled-coil. The enthalpy and entropy changes depend on the length and nature
      of the loop region. For a peptide with three helical sections: protonated
      AcA(14)KG(3)A(14)KG(3)A(14)K; a coiled-coil bundle with three helices side-by
      side is substantially less stable than a geometry with two helices in an
      antiparallel coiled-coil and the third helix collinear with one of the other two.

PMID- 17521915
TI  - Developing limited proteolysis and mass spectrometry for the characterization of
      ribosome topography.
AB  - An approach that combines limited proteolysis and matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) has been developed to probe
      protease-accessible sites of ribosomal proteins from intact ribosomes.
      Escherichia coli and Thermus thermophilus 70S ribosomes were subjected to limited
      proteolysis using different proteases under strictly controlled conditions.
      Intact ribosomal proteins and large proteolytic peptides were recovered and
      directly analyzed by MALDI-MS, which allows for the determination of proteins
      that are resistant to proteolytic digestion by accurate measurement of molecular
      weights. Larger proteolytic peptides can be directly identified by the
      combination of measured mass, enzyme specificity, and protein database searching.
      Sucrose density gradient centrifugation revealed that the majority of the 70S
      ribosome dissociates into intact 30S and 50S subunits after 120 min of limited
      proteolysis. Thus, examination of ribosome populations within the first 30 to 60
      min of incubation provides insight into 70S structural features. Results from E.
      coli and T. thermophilus revealed that a significantly larger fraction of 50S
      ribosomal proteins have similar limited proteolysis behavior than the 30S
      ribosomal proteins of these two organisms. The data obtained by this approach
      correlate with information available from the high-resolution crystal structures
      of both organisms. This new approach will be applicable to investigations of
      other large ribonucleoprotein complexes, is readily extendable to ribosomes from
      other organisms, and can facilitate additional structural studies on ribosome
      assembly intermediates.

PMID- 17521917
TI  - Nonergodicity in electron capture dissociation investigated using hydrated ion
      nanocalorimetry.
AB  - Hydrated divalent magnesium and calcium clusters are used as nanocalorimeters to
      measure the internal energy deposited into size-selected clusters upon capture of
      a thermally generated electron. The infrared radiation emitted from the cell and
      vacuum chamber surfaces as well as from the heated cathode results in some
      activation of these clusters, but this activation is minimal. No measurable
      excitation due to inelastic collisions occurs with the low-energy electrons used
      under these conditions. Two different dissociation pathways are observed for the
      divalent clusters that capture an electron: loss of water molecules (Pathway I)
      and loss of an H atom and water molecules (Pathway II). For Ca(H(2)O)(n)(2+),
      Pathway I occurs exclusively for n >or= 30 whereas Pathway II occurs exclusively
      for n <or= 22 with a sharp transition in the branching ratio for these two
      processes that occurs for n approximately 24. The number of water molecules lost
      by both pathways increases with increasing cluster size reaching a broad maximum
      between n = 23 and 32, and then decreases for larger clusters. From the number of
      water molecules that are lost from the reduced cluster, the average and maximum
      possible internal energy is determined to be approximately 4.4 and 5.2 eV,
      respectively, for Ca(H(2)O)(30)(2+). This value is approximately the same as the
      calculated ionization energies of M(H(2)O)(n)(+), M = Mg and Ca, for large n
      indicating that the vast majority of the recombination energy is partitioned into
      internal modes of the ion and that the dissociation of these ions is statistical.
      For smaller clusters, estimates of the dissociation energies for the loss of H
      and of water molecules are obtained from theory. For Mg(H(2)O)(n)(2+), n = 4-6,
      the average internal energy deposition is estimated to be 4.2-4.6 eV. The maximum
      possible energy deposited into the n = 5 cluster is <7.1 eV, which is
      significantly less than the calculated recombination energy for this cluster.
      There does not appear to be a significant trend in the internal energy deposition
      with cluster size whereas the recombination energy is calculated to increase
      significantly for clusters with fewer than 10 water molecules. These, and other
      results, indicate that the dissociation of these smaller clusters is nonergodic.

PMID- 17521918
TI  - What guides MHC-restricted TCR recognition?
AB  - MHC-encoded molecules govern adaptive immune responses by presenting peptides to
      T cell receptors (TCRs). Based on TCR-MHC crystal structures, we revisit the
      extent of TCR binding degeneracy, a property with important biological
      consequences because the diversity of TCR ligands that can be encountered exceeds
      the number of T cell clones present in a person at any one time. We also discuss
      whether the approximate diagonal binding of TCR on MHC molecules is due to an
      intrinsic property of the TCR variable regions, or results from the action of the
      CD4 and CD8 coreceptors during intrathymic T cell selection. Finally, we discuss
      how MHC restriction of antigen recognition might have emerged during evolution.

PMID- 17521919
TI  - Involvement of Gly 311 residue on substrate discrimination, pH and temperature
      dependency of recombinant Staphylococcus xylosus lipase: a study with emulsified
      substrate.
AB  - The importance of microbial lipases like the staphylococcal ones, results not
      only from their significance implication in the bacterial lipid metabolism but
      also their involvement in some pathogenic processes. The aminoacid sequence of
      the mature Staphylococcus xylosus lipase (SXL) shows 99.7% identity with the
      mature aminoacid sequence of Staphylococcus simulans lipase (SSL) with one
      substitution of Gly311 by Val. In spite of this high homology, the two lipases
      present significant differences in the specific activities and in the optimal
      temperature of action. In order to check the importance of the residue 311, we
      substituted, using site-directed mutagenesis, the Gly311 of S. xylosus lipase
      (SXL) by Leu, Trp, Asp, or Lys. The mutants SXL-G311L, SXL-G311W, SXL-G311D, and
      SXL-G311K were expressed in Escherichia coli BL21 (DE3) and purified to
      homogeneity. A comparative study of the biochemical properties of the wild-type
      SXL (SXL-WT) and the mutants was performed and show that an increase in the size
      of the 311 aminoacid side chain residue was accompanied by a decrease of lipase
      activity. The absence of lipase activity observed with the mutant SXL-G311W was
      probably due to the inaccessibility of substrate to interact with the catalytic
      serine. On the other hand, the SXL-G311L mutant, which presents a significant
      decrease on the lipase activity, displays a novel action towards phospholipids.
      Furthermore, the mutant SXL-G311L becomes also stable to extreme pH and displays
      a half life of 280 min after incubation at 50 degrees C. The purified SXL-G311D
      and SXL-G311K mutants show distinct pH profiles. The SXL-G311D mutant is
      optimally active at pH 6.5, whereas, the SXL-G311K mutant is active at pH 9.5. In
      addition, these two mutants show an important decrease in the specific activities
      that generates a decrease in the catalytic efficiency (k(cat)/K(m)app.). We can
      essentially notice that the SXL-G311K mutant displays a 33- or 44-fold decrease
      in k(cat)/K(m)app. values compared to the SXL-WT, when using TC(4) or TC(8) as
      substrate, respectively.

PMID- 17521920
TI  - Development of a bacterial system for high yield expression of fully functional
      adrenal cytochrome b561.
AB  - Adrenal cytochrome b561 (cyt b561) is the prototypical member of an emerging
      family of proteins that are distributed widely in vertebrate, invertebrate and
      plant tissues. The adrenal cytochrome is an integral membrane protein with two b
      type hemes and six predicted transmembrane helices. Adrenal cyt b561 is involved
      in catecholamine biosynthesis, shuttling reducing equivalents derived from
      ascorbate. We have developed an Escherichia coli system for expression,
      solubilization and purification of the adrenal cytochrome. The spectroscopic and
      redox properties of the purified recombinant protein expressed in this
      prokaryotic system confirm that the cytochrome retains a native, fully functional
      form over a wide pH range. Mass spectral analysis shows that the N-terminal
      signal peptide is intact. The new bacterial expression system for cyt b561 offers
      a sixfold improvement in yield and other substantial advantages over existing
      insect and yeast cell systems for producing the recombinant cytochrome for
      structure-function studies.

PMID- 17521921
TI  - Diet during pregnancy and risk of preeclampsia or gestational hypertension.
AB  - PURPOSE: We sought to examine associations of first-trimester intake of calcium,
      n-3 and n-6 fatty acids, trans fatty acids, magnesium, folate, and vitamins C, D,
      and E with preeclampsia (PE) and gestational hypertension (GH). METHODS: We
      studied associations of diet with PE or GH among 1718 women in the prospective
      cohort study Project Viva, using logistic regression and adjusting for maternal
      age, prepregnancy body mass index, first trimester systolic blood pressure,
      race/ethnicity, education, and parity. We assessed first-trimester diet using a
      validated semiquantitative food frequency questionnaire. RESULTS: A total of 59
      (3%) women developed PE, and 119 developed (7%) GH. We found a somewhat-lower
      risk of PE associated with higher intake of the elongated n-3 fatty acids
      docosahexaenoic and eicosapentaenoic acids (odds ratio [OR] 0.84, 95% confidence
      interval [95% CI]: 0.69-1.03 per 100 mg/day), fish (OR 0.91, 95% CI 0.75-1.09 per
      serving/day), and the ratio of docosahexaenoic + eicosapentaenoic to arachadonic
      acid (OR 0.82, 95% CI 0.66-1.01). We did not observe a lower risk of GH or PE
      with a greater intake of calcium; vitamin C, D, or E; milk; magnesium; folate; or
      with lower intake of n-6 or trans fatty acids. CONCLUSIONS: Our results support a
      potential benefit for elongated n-3 fatty acids in preventing preeclampsia.

PMID- 17521922
TI  - Socioeconomic position in childhood and adulthood and weight gain over 34 years:
      the Alameda County Study.
AB  - PURPOSE: Socioeconomic position (SEP) has been shown to be related to obesity and
      weight gain, especially among women. It is unclear how different measures of
      socioeconomic position may impact weight gain over long periods of time, and
      whether the effect of different measures vary by gender and age group. We
      examined the effect of childhood socioeconomic position, education, occupation,
      and log household income on a measure of weight gain using individual growth
      mixed regression models and Alameda County Study data collected over thirty four
      years(1965-1999). METHODS: Analyses were performed in four groups stratified by
      gender and age at baseline: women, 17-30 years (n = 945) and 31-40 years (n =
      712); men, 17-30 years (n = 766) and 31-40 years (n = 608). RESULTS: Low
      childhood SEP was associated with increased weight gain among women 17-30 (0.13
      kg/year, p < 0.001). Low educational status was associated with increased weight
      gain among women 17-30 (0.14 kg/year, p = 0.030), 31-40 (0.14 kg/year, p =
      0.014), and men 17-30 (0.20 kg/year, p = 0.001). CONCLUSION: Log household income
      was inversely associated with weight gain among men 31-40 (-0.10 kg/yr, p =
      0.16). Long-term weight gain in adulthood is associated with childhood SEP and
      education in women and education and income in men.

PMID- 17521923
TI  - CD83 expression in sea bream macrophages is a marker for the LPS-induced
      inflammatory response.
AB  - CD83, a cell surface membrane glycoprotein member of the Ig superfamily which is
      commonly used as standard surface marker for dendritic cells, was cloned from
      gilthead sea bream macrophages using degenerate primers against conserved motifs
      of known CD83 sequences. The obtained cDNA contains an open reading frame of 669
      nucleotides that translate into a 222 amino acid putative peptide. The deduced
      protein sequence shows conservation of features shared by vertebrate CD83 and
      multiple alignment with fish CD83 sequences reveals high homology. In cultured
      sea bream macrophages CD83 mRNA expression was significantly enhanced in a dose-
      and time-dependent fashion after stimulation with Escherichia coli LPS. These
      results indicate that in fish, macrophages express high levels of CD83 mRNA after
      LPS exposure and CD83 is therefore a good marker for activated mature myeloid
      cells in fish.

PMID- 17521924
TI  - Different neural systems adjust motor behavior in response to reward and
      punishment.
AB  - Individuals use the outcomes of their actions to adjust future behavior. However,
      it remains unclear whether the same neural circuits are used to adjust behavior
      due to rewarding and punishing outcomes. Here we used functional magnetic
      resonance imaging (fMRI) and a reward-providing reaction time task to investigate
      the adaptation of a simple motor response following four different outcomes
      (delivery versus omission and monetary gain versus loss). We found that
      activation in the thalamus and insula predicted adjustments of motor responses
      due to outcomes that were cued and delivered, whereas activation in the ventral
      striatum predicted such adjustments when outcomes were cued but omitted. Further,
      activation of OFC predicted improvement after all punishing outcomes, independent
      of whether they were omitted rewards or delivered punishments. Finally, we found
      that activity in anterior cingulate predicted adjustment after delivered
      punishments and activity in dorsal striatum predicted adaptation after delivered
      rewards. Our results provide evidence that different but somewhat overlapping
      circuits mediate the same behavioral adaptation when it is driven by different
      incentive outcomes.

PMID- 17521925
TI  - Treatment of proximal humeral chondrosarcoma with resection and allograft.
AB  - Chondrosarcoma of the proximal humerus is an uncommon malignant bone tumor, and
      limited information is available about treatment. We retrospectively reviewed 31
      patients treated by resection and replacement with allograft implants during the
      past 24 years. The patients were followed up for an average of more than 16
      years. Despite some allograft complications, the overall success rate for the
      grafts was 77%, and patient survival was 96%. Only 1 patient died. Two patients
      required amputation for local recurrences, and the remainder did reasonably well
      despite some functional problems. On the basis of this study and by comparison
      data, we believe that proximal humeral chondrosarcomas are less malignant than
      chondrosarcomas in other sites. In comparing them against 26 metallic implants,
      we believe that resection and allograft implantation remains a generally
      successful treatment, although the improvement of the metallic devices over the
      years has made this technique more available and acceptable.

PMID- 17521926
TI  - Corpus callosotomy: a palliative therapeutic technique may help identify
      resectable epileptogenic foci.
AB  - Corpus callosotomy has a long history as a palliative treatment for intractable
      epilepsy. Identification of a single epileptogenic zone is critical to performing
      successful resective surgery. We describe three patients in which corpus
      callosotomy allowed recognition of unapparent seizure foci, leading to subsequent
      successful resection. We retrospectively reviewed our epilepsy surgery database
      from 2003 to 2005 for children who had a prior callosotomy and were candidates
      for focal resection. All underwent magnetic resonance imaging and scalp video
      electroencephalograph monitoring, and two had magnetoencephalography,
      electrocorticography and/or intracranial video electroencephalograph monitoring.
      The children were 8 and 9 years old, and seizure onset varied from early infancy
      to early childhood. One child had a history of head trauma preceding seizure
      onset, one had a large intracerebral infarct and dysplastic cortex in the
      contralateral frontal lobe, and the other had an anterior temporal lobe resection
      without improvement in seizure frequency. After medical management failed,
      callosotomy was performed with the expectation of decreasing the seizure types
      affecting both hemispheres. Following transection of the callosal fibers, a
      single focus was recognized and resected, with resultant dramatic improvement in
      seizure control. In medically refractory epilepsy, where rapid secondary
      bisynchrony is suspected but the electroencephalograph is non-localizing,
      callosotomy should be considered as a means of treating generalized seizure
      types, but may also assist in identifying potentially operable seizure foci.
      Study limitations include its retrospective nature and cohort size. The findings,
      however, suggest the need for prospective, systematic, well-controlled studies of
      the use of corpus callostomy in this intractable patient population.

PMID- 17521927
TI  - Ser-10 phosphorylated histone H3 is involved in cytokinesis as a chromosomal
      passenger.
AB  - Ser-10 phosphorylation of histone H3 is revealed to be relative to chromosome
      condensation at prophase during mitosis. In this report, we demonstrate using
      immunofluorescence microscopy that the subcellular distribution of the Ser-10
      phosphorylated histone H3 was similar to that characteristic of chromosomal
      passenger proteins during the terminal stages of cytokinesis. Co
      immunoprecipitation indicates that the Ser-10 phosphorylated histone H3 is
      associated with the aurora B, and both of the proteins were compacted into a
      complex with special ternary structure located in the centre of the midbody. When
      the level of the Ser-10 phosphorylated histone H3 was reduced by RNA
      interference, the cells formed an aberrant midbody and could not complete
      cytokinesis successfully. This evidence suggests that Ser-10 phosphorylated
      histone H3 is a chromosomal passenger protein and plays a crucial role in
      cytokinesis.

PMID- 17521928
TI  - Salicylic acid-induced taxol production and isopentenyl pyrophosphate
      biosynthesis in suspension cultures of Taxus chinensis var. mairei.
AB  - The influences of salicylic acid (SA) on taxol production and isopentenyl
      pyrophosphate (IPP) biosynthesis pathways in suspension cultures of Taxus
      chinensis var. mairei were investigated by adding SA and mevastatin (MVS), a
      highly specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase in the
      mevalonate pathway for IPP biosynthesis, into the culture systems. The cell death
      and taxol production were induced upon the introduction of SA, and 20mg/l was
      proved to be the optimal SA concentration in terms of the less damage to Taxus
      cells and marked activation of phenylalanine ammonia lyase (PAL). In the
      coexistence of SA (20mg/l) and MVS (100 nmol/l), the taxol content (1.626 mg/g
      dry wt) was higher than that (0.252 mg/g dry wt) of the MVS-treated system but
      almost equal to that (1.581 mg/g dry wt) of the SA-treated system. It is thus
      inferred that the activated non-mevalonate pathway should be responsible for the
      formation of IPP in taxol biosynthesis in the presence of SA.

PMID- 17521929
TI  - Acute inhibition of calcineurin restores associative learning and memory in
      Tg2576 APP transgenic mice.
AB  - Misfolded amyloid beta peptide (Abeta) is a pathological hallmark of Alzheimer's
      disease (AD), a neurodegenerative illness characterized by cognitive deficits and
      neuronal loss. Transgenic mouse models of Abeta over-production indicate that
      Abeta-induced cognitive deficits occur in the absence of overt neuronal death,
      suggesting that while extensive neuronal death may be associated with later
      stages of the human disease, subtle physiological changes may underlie initial
      cognitive deficits. Therefore, identifying signaling elements involved in those
      Abeta-induced cognitive impairments that occur prior to loss of neurons may
      reveal new potential pharmacological targets. Here, we report that the enzymatic
      activity of calcineurin, a key protein phosphatase involved in phosphorylation
      dependent kinase activity crucial for synaptic plasticity and memory function, is
      upregulated in the CNS of the Tg2576 animal model for Abeta over-production.
      Furthermore, acute treatment of Tg2576 mice with the calcineurin inhibitor FK506
      (10mg/kg i.p.) improves memory function. These results indicate that calcineurin
      may mediate some of the cognitive effects of excess Abeta such that inhibition of
      calcineurin shall be further explored as a potential treatment to reverse
      cognitive impairments in AD.

PMID- 17521930
TI  - Influence of antiplatelet therapy on cerebral micro-emboli after carotid
      endarterectomy using postoperative transcranial Doppler monitoring.
AB  - AIM: To study the effect of different antiplatelet regimens (APT) on the rate of
      postoperative TCD registered micro-embolic signals (MES) following carotid
      endarterectomy (CEA). DESIGN: Prospective, randomised, double-blinded, pilot
      study. METHODS: The study group of 102 CEA patients (76 men, mean age 66.8 years)
      was randomised to routine Asasantin (Dipyridamole 200mg/Aspirin 25mg) twice daily
      (group I; n=39), Asasantin plus 75 mg Clopidogrel once daily (group II; n=33), or
      Asasantin plus Rheomacrodex (Dextran 40) 100g/L iv; 500 ml (group III; n=30). TCD
      monitoring of the ipsilateral middle cerebral artery for the occurrence of MES
      was performed intra-operatively and during the second postoperative hour
      following CEA. Primary endpoints were the rate of postoperative emboli and the
      occurrence of cerebrovascular complications. Secondary endpoint was any adverse
      bleeding. RESULTS: There were no deaths or major strokes. We observed 2
      intraoperative TIA's (group II and III) and 1 postoperative minor stroke (group
      I). In comparison with placebo, Clopidogrel or Rheomacrodex in addition to
      Asasantin produced no significant reduction in the number of postoperative MES.
      There was no significant difference between the number of postoperative MES and
      different antiplatelet regimens. The incidence of bleeding complications was not
      significantly different between the 3 APT groups. CONCLUSION: In the present
      study, we could not show a significant influence of different antiplatelet
      regimens on TCD detected postoperative embolization following CEA.

PMID- 17521931
TI  - Significance of the early postoperative duplex result in infrainguinal vein
      bypass surveillance.
AB  - BACKGROUND: Duplex surveillance of infrainguinal vein grafts may not be
      efficient. METHODS: Consecutive patients who had received infrainguinal vein
      grafts were enrolled in a duplex surveillance program. A first scan at 6 weeks
      after surgery categorized grafts into four groups: (a) low risk grafts, (b) mild
      flow disturbance, (c) intermediate stenosis and (d) critical stenosis. Disease
      progression was assessed over time. RESULTS: Of 364 grafts followed-up for a
      median of 23 months, 236 (65%) had no flow abnormality at 6-weeks, and had a 40
      month cumulative patency rate of 82%. The remaining 128 (35%) grafts had a flow
      disturbance. Of 29 critical stenoses, 15 were repaired, 11 occluded and three did
      not change. Of 57 intermediate lesions, 32 progressed to critical, nine occluded,
      two were repaired and 14 did not change or improved. Of 42 mild lesions, 16
      progressed to a higher grade, four occluded and 22 did not change or improved.
      There was no significant difference in graft patency between grafts with repaired
      stenoses and those without stenoses, but grafts with untreated critical stenoses
      were associated with lower patency (p<0.001). CONCLUSIONS: A duplex scan 6 weeks
      after operation can predict those patients who require continuing duplex
      surveillance.

PMID- 17521932
TI  - Portable mass spectrometry for measurement of anaesthetic agents and methane in
      respiratory gases.
AB  - Monitoring the composition of gases breathed by anaesthetised patients requires
      measurement methods with fast responses, high accuracy and good reliability.
      There is also an increasing demand for systems to be able to monitor more than
      one target analyte simultaneously, but some gas analysers can be sensitive to the
      presence of methane gas in exhaled breath, consequently leading to inaccurate
      measurements of the anaesthetic agent. This study investigated the feasibility of
      employing portable quadrupole mass spectrometry to monitor volatile anaesthetic
      agents (halothane, isoflurane and sevoflurane), methane accumulation in
      anaesthetic rebreathing systems, and inspired and exhaled carbon dioxide and
      oxygen concentrations during equine anaesthesia in a clinical setting. The
      volatile anaesthetic agents were easily measurable and methane was detectable.
      The instrument had an advantage over short wavelength infrared absorption
      spectrometry analysers because it could monitor anaesthetic agents and other
      respiratory gases simultaneously and at extremely low concentrations, although
      further optimisation is required.

PMID- 17521933
TI  - Applications of DNP-NMR for the measurement of heteronuclear T1 relaxation times.
AB  - Measurement of heteronuclear spin-lattice relaxation times is hampered by both
      low natural abundance and low detection sensitivity. Combined with typically long
      relaxation times, this results in extended acquisition times which often renders
      the experiment impractical. Recently a variant of dynamic nuclear polarisation
      has been demonstrated in which enhanced nuclear spin polarisation, generated in
      the cryo-solid state, is transferred to the liquid state for detection. Combining
      this approach with small flip angle pulse trains, similar to the FLASH-T(1)
      imaging sequence, allows the rapid determination of spin-lattice relaxation
      times. In this paper we explore this method and its application to the
      measurement of T(1) for both carbon-13 and nitrogen-15 at natural abundance. The
      effects of RF inhomogeneity and the influence of proton decoupling in the context
      of this experiment are also investigated.

PMID- 17521934
TI  - Gill (Na+,K+)-ATPase in diadromous, freshwater palaemonid shrimps: species
      specific kinetic characteristics and alpha-subunit expression.
AB  - To better comprehend physiological adaptation to dilute media and the molecular
      mechanisms underlying ammonia excretion in palaemonid shrimps, we characterized
      the (Na+,K+)-ATPase from Macrobrachium amazonicum gills, disclosing high- (K(0.5)
      = 4.2+/-0.2 micromol L(-1); V = 33.9+/-1.9 U mg(-1)) and low-affinity (K(0.5) =
      0.144+/-0.010 mmol L(-1); V = 232.9+/-15.3 U mg(-1)) ATP hydrolyzing sites.
      Stimulation by Na+ (K(0.5) = 5.5+/-0.3 mmol L(-1); V = 275.1+/-15.1 U mg(-1)),
      Mg2+ (K(0.5) = 0.79+/-0.06 mmol L(-1); V = 261.9+/-18.3 U mg(-1)), K+ (K(M) =
      0.88+/-0.04 mmol L(-1); V = 271.8+/-10.9 U mg(-1)) and NH4(+) (K(M) = 5.0+/-0.2
      mmol L(-1); V = 385.9+/-15.8 U mg(-1)) obeys single saturation curves, activity
      being stimulated synergistically by NH4(+) and K+. There is a single K+ binding
      site, NH4(+) binding to a second, exclusive site, stimulating activity by 33%,
      modulating K+ affinity. (Na+,K+)-ATPase activity constitutes approximately 80% of
      total ATPase activity (K(Iouabain) = 147.5+/-8.9 micromol L(-1)); Na+-, K+-, Ca2+
      , V- and F(o)F(1)-ATPases are also present. M. amazonicum microsomal fractions
      possess approximately 2-fold less (Na+,K+)-ATPase alpha-subunit than M. olfersi,
      consistent with a 2.6-fold lower specific activity. These differences in (Na+,
      K+)-ATPase stimulation by ATP and ions, and specific activities of other ATPases,
      suggest the presence of distinct biochemical adaptations to life in fresh water
      in these related species.

PMID- 17521935
TI  - Feeding rates and absorption efficiencies of four species of sea urchins (genus
      Echinometra) fed a prepared diet.
AB  - Four closely related species of sea urchins belonging to the genus Echinometra,
      Echinometra sp. A (Ea), E. mathaei (Em), E. sp. C (Ec), and E. oblonga (Eo),
      occur sympatrically but in different microhabitats on Okinawan coral reefs.
      Feeding rates and absorption efficiencies of the four species were investigated
      in the laboratory by feeding sea urchins ad libitum a diet prepared from turf
      algae and agar over a 7-day period. Feeding rates differed significantly among
      the four species of Echinometra (Ea > Em approximately = Ec > Eo). Absorption
      efficiencies of protein and lipid did not differ significantly among the four
      species. Carbohydrate, a major nutrient component in the diet, was absorbed by
      the four species at significantly different efficiencies (Eo > Ec approximately =
      Em > Ea), which resulted in similar interspecific differences in absorption
      efficiencies of dry matter, total organic matter, and energy. The amount of
      nutrients absorbed from the diet was directly related to the feeding rate,
      indicating that the increase in absorption efficiency was not sufficient to
      completely compensate for low feeding rate. The interspecific difference in
      physiological performance in relation to feeding and absorption is consistent
      with taxonomic differentiation among the four species.

PMID- 17521936
TI  - Ex vivo inhibitory effect on tilapia LDL oxidation and hypolipidemia properties
      of Glycine tomentella root extract.
AB  - The ethanolic extract of I-Tiao Gung (GT-E) (Glycine tomentella root extract) was
      found to reduce the oxidative rate and prolonged lag phase of LDL in human (Homo
      sapiens) and tilapia (Oreochromis mossambicus). The in vivo effect of GT-E was
      determined using tilapia as a model. Hyperlipidemia and hypercholesterolemia were
      induced in fish by feeding commercial feed daily at 2% body mass for 8 weeks, or
      at 1% body mass for 12 weeks. Thirty two adult male tilapia were randomly divided
      into two groups and fed with feed containing 1% (w/w) GT-E or control diet for 12
      weeks. Specific growth rate was similar between the GT-E group and the control
      group. Total triacylglycerol, total cholesterol and low-density lipoprotein
      cholesterol (LDL-C) in plasma of the GT-E group were significantly lower, while
      plasma total antioxidant status was significantly higher than those of the
      control group. GT-E fed fish had longer lag phase of Cu2+-induced LDL oxidation
      and retained more alpha-tocopherol in LDL particles than the control fish. LDL
      from the GT-E group had more monounsaturated fatty acids and less polyunsaturated
      fatty acids than the control group indicative of its effect on fatty acids
      metabolism. GT-E demonstrated hypolipidemic and hypocholesterolemic effects and
      inhibiting LDL oxidation in tilapia similar to the effects in mammals, thus
      tilapia can serve as a surrogate animal model for prescreening anti
      atherosclerosis effect of natural products.

PMID- 17521937
TI  - Modulation of sterol regulatory element binding protein-2 in response to rapid
      follicle development in chickens.
AB  - We investigated the expression profiles of sterol regulatory element binding
      proteins (SREBPs) and their related genes in chicken developing follicle
      membranes, from the small white follicle (SWF) stage to the Follicle 1 (F1)
      stage. Expression of SREBP-2 was significantly increased in the rapid stages of
      follicle development, however, no significant change in SREBP-1 mRNA expression
      was observed during follicle development. Immunoreactive SREBP-2 protein levels
      isolated from nuclear extracts in rapid growth stages, particularly in Follicle
      2, were higher than those in SWF and small yellow follicle (SYF). In contrast,
      SREBP-1 immunoreactive protein levels were only slightly changed over all stage
      of follicle development. 3-Hydroxy-3-methylglutaryl CoA reductase (HMGR) mRNA
      levels significantly increased in the rapid stages of follicle development,
      suggesting that SREBP-2 controls the biosynthesis of cholesterol in follicles.
      LDL receptor and LDL receptor related protein 1 mRNA also tended to increase with
      follicular development, however, expression of LDL receptor relative with eight
      ligand binding repeats (LR8) was only slightly affected by SREBP-2. Liver X
      receptor alpha (LXR alpha) was expressed in chicken follicles; its expression
      patterns corresponded with SREBP-2 gene expression. These results suggest that
      SREBP-2, which might be regulated by LXRalpha, is involved in the rapid growth
      stages of follicle development in avian species.

PMID- 17521940
TI  - [Transfusion protocols in hematopoietic stem cell allogeneic transplantation].
AB  - Hematopoietic stem cell (HSC) allogeneic transplantation is now commonly used as
      a therapeutic tool in patients with certain types of hematologic malignancies.
      Such patients, on account of severe pre-graft conditioning regimens, present with
      severe marrow aplasia justifying specific transfusion care. Given a complex
      immunological situation (immediately after transplantation, co-existence of two
      cell populations with different immunohematological characteristics), transfusion
      protocols must rest on clear and well-defined recommendations. Recent transfusion
      recommendations in settings of HSC allogeneic transplantation have defined
      criteria for the choice of blood products (red blood cell concentrates, plasma
      and platelet concentrates) depending on recipient and graft immunohematological
      characteristics (minor/major/mixed ABO compatibility/incompatibility and time of
      transplantation). Transfusion instructions are summarized in a synthesis document
      entitled : "Instructions for transfusion following HSC allogeneic
      transplantation". This document specifies the immunohematological characteristics
      of blood products and various transfusion protocols (systematic irradiation,
      negative CMV, etc.). This document is used by the teams who distribute blood
      products, for selection purposes, as well as by the medical transfusion team when
      they perform ultimate pre-transfusion control steps.

PMID- 17521938
TI  - Energizing miRNA research: a review of the role of miRNAs in lipid metabolism,
      with a prediction that miR-103/107 regulates human metabolic pathways.
AB  - MicroRNAs (miRNAs) are powerful regulators of gene expression. Although first
      discovered in worm larvae, miRNAs play fundamental biological roles-including in
      humans-well beyond development. MiRNAs participate in the regulation of
      metabolism (including lipid metabolism) for all animal species studied. A review
      of the fascinating and fast-growing literature on miRNA regulation of metabolism
      can be parsed into three main categories: (1) adipocyte biochemistry and cell
      fate determination; (2) regulation of metabolic biochemistry in invertebrates;
      and (3) regulation of metabolic biochemistry in mammals. Most research into the
      'function' of a given miRNA in metabolic pathways has concentrated on a given
      miRNA acting upon a particular 'target' mRNA. Whereas in some biological contexts
      the effects of a given miRNA:mRNA pair may predominate, this might not be the
      case generally. In order to provide an example of how a single miRNA could
      regulate multiple 'target' mRNAs or even entire human metabolic pathways, we
      include a discussion of metabolic pathways that are predicted to be regulated by
      the miRNA paralogs, miR-103 and miR-107. These miRNAs, which exist in vertebrate
      genomes within introns of the pantothenate kinase (PANK) genes, are predicted by
      bioinformatics to affect multiple mRNA targets in pathways that involve cellular
      Acetyl-CoA and lipid levels. Significantly, PANK enzymes also affect these
      pathways, so the miRNA and 'host' gene may act synergistically. These predictions
      require experimental verification. In conclusion, a review of the literature on
      miRNA regulation of metabolism leads us believe that the future will provide
      researchers with many additional energizing revelations.

PMID- 17521941
TI  - [Health care units in the French blood banks, why?].
AB  - In France for several years, many patients have been treated in Blood Transfusion
      Centers belonging to the EFS. This partnership between public hospitals and EFS
      is appreciated by the patients who find a competent staff in transfusion and
      apheresis process, in a more pleasant environment than in hospital. There is a
      total of 93 Health Care Units in Blood Transfusion Centers. Sixty-three of these
      Health Care Units perform only transfusions and bleeding. In the remaining 30
      Health Care Units apheresis, peripheral blood hematopoietic stem, cell
      harvesting, plasmatic exchanges and extracorporeal photopheresis are also
      performed. Despite the perfect fit between hospital needs, comfort and easiness
      for patients, an economical problem remains. At the present time, the
      reimbursement rate by national health insurance is below the real cost. If
      unsolved, this discrepancy could force an end to this beneficial partnership.

PMID- 17521942
TI  - [The future of blood transfusion: between breaking off and commercialisation
      risks].

PMID- 17521943
TI  - [Bacterial contamination: should it be detected or inactivated?].
AB  - The main cause of adverse events secondary to the transfusion of platelet
      concentrates (PC) is due to bacterial contamination. The detection of bacteria in
      PC is not associated with a beneficial effect in terms of prevention of fatal
      septic events. Inactivation of pathogen in PC using photochemical techniques is
      targeted not only to bacteria but also to a wide spectrum of viruses,
      spirochetes, parasites and leukocytes. Pathogen inactivation is a pro-active
      method which anticipates the contamination of the blood pool by emerging
      pathogens.

PMID- 17521944
TI  - [Multiple apheresis].
AB  - Multiple apheresis makes it possible to obtain at least two labile blood
      components from a single donor using a cell separator. It can be either
      multicomponent apheresis leading to the preparation of at least two different
      blood component types or red blood cell apheresis providing two identical red
      blood cell concentrates. These techniques available in addition to whole blood
      donation, are modifying collection strategies in many Etablissements Francais du
      Sang and will contribute to improve stock logistics in the future. In areas with
      insufficient stock, these procedures will help achieve blood component self
      sufficiency. The author first describes the principle underlying different-
      current or future--techniques as well as their advantages and drawbacks. He
      finally addresses the potential impact of these processes on the evolution of
      blood collection and the advantages to be gained.

PMID- 17521945
TI  - [Biometric and histological study of human, porcine and sheep internal thoracic
      arteries (reflections on their use in revascularization of arteries of less than
      four millimetres diameter)].
AB  - In order to enhance the knowledge of the internal thoracic arteries of pig,
      sheep, and man, allowing to constitute a fundamental basis as for the current and
      later applications in the interventions in surgery of revascularization of the
      arteries of less than four millimetre of diameter, a biometric and histological
      comparative study of these arteries was carried out. Forty human corpses, 27 men
      and 13 women (mean age 75+/-6 years) were dissected, alike with three pigs
      respectively weighing 80 kg, 80 kg and 84 kg and four sheep weighing 70 kg each.
      The left and right internal thoracic arteries were harvested: exposure over the
      entire length and remote dissection before excision. At the same time their
      internal lengths and gauges were measured. The internal thoracic artery (ITA) of
      human has an average useful length of 18 cm and an average internal gauge close
      to 1.5 mm. ITA of the pig has an average length of 27 cm and an average internal
      gauge close to 2.8 mm. The ITA of the sheep has an average length of 18 cm with
      an average internal gauge close to 1 mm. The porcine Internal Thoracic Artery is
      an elastic artery like its human counterpart. Many elastic fibres and few smooth
      muscle cells are present in the media. On the other hand, the internal thoracic
      artery of the sheep has a mixed structure. Its media contains more smooth muscle
      cells than elastic fibres.

PMID- 17521946
TI  - [Giant cell tumors of the tendon sheath of the hand: 32 cases].
AB  - Giant cell tumors of tendon sheath (GCTTS) represent a localised form of
      pigmented villonodular synovitis. They are usually found in the hand (80% of
      cases) where it represents the second most common tumor of the soft parts after
      the ganglion cyst. Its surgical treatment is sometimes difficult because of local
      extension and the invasion of vital digital structures. We report a retrospective
      study over 10 years of 32 cases of GCTTS with an average age of 35 years and a
      sex-ratio of 1. The reason for consultation was the presence of a digital mass,
      associated with an impairment of finger flexion in 43,7% of patients. A palmar
      localisation was found in 56,2%, especially in the fifth ray (62,5%) and at the
      level of the distal phalanx (68,7%). Radiological changes were observed in 4
      cases. All patients were treated surgically. Macroscopically the lesion presented
      as an encapsulated tumor, polylobulated and yellow-brownish which invaded the
      skin (1 case), extended into the sheath of the flexor tendons (3 cases) and under
      the extensor tendon (4 cases). In the post operative follow up we noted one case
      of hypoaesthesia of the pulp and three cases of stiffness of the proximal
      interphalangeal joint. No skin necrosis was found. With a 4 year average follow
      up (10 months - 9 years), we noted three reccurrences (9,3%) which were all
      surgically managed. After analysis of the literature, the authors will describe
      the clinical aspects and the therapeutic difficulties of this condition.

PMID- 17521947
TI  - [Psychosomatical approach to Hyperemesis gravidarum].
AB  - Vomiting of pregnancy is a physiological symptom of the first trimester and is a
      frequent reason for consultation in emergency as well as hospitalization in the
      severe forms (Hyperemesis gravidarum). Though strong the aversion usually
      developed against the hospitalized patients for H. gravidarum may be, it is
      important to understand the distress of these women with a symptom difficult to
      endure, which often reflects a psychical conflict with respect to their
      pregnancy. The gynecologist must be the somatic doctor who deals with the symptom
      and its sometimes disastrous clinical consequences, whereas the psychologist or
      the psychiatrist plays a fundamental role in this pathology. Indeed, he will lead
      the patient to work on how she feels her pregnancy, to give it a place in her
      personal history and to understand her contradictory feelings with regard to this
      pregnancy.

PMID- 17521948
TI  - [Increased nuchal translucency with normal karyotype].
AB  - Nuchal translucency (NT) measurement in first trimester screening between 11 and
      14 weeks' gestation has now been clearly identified as a marker for aneuploidies
      and in particular for trisomy 21. Even in the absence of aneuploidy increased
      fetal nuchal translucency has been shown to be a marker for fetal heart
      malformations and numerous other fetal defects and genetic syndromes when the
      measure is>or=95th centile which is around 3,5 mm for each gestational age.
      Fetuses with NT thickness above the 99th centile and normal karyotype have a high
      risk of adverse prenatal outcome and this increase in risk is exponential as the
      nuchal translucency measurement increases. However, among children born alive
      with normal ultrasound at 22 weeks of gestation, there was no significant
      association between NT thickness and development at 2 years as assessed by
      clinical examination and ASQ scores, when with a control population. Counselling
      should emphasize that when the karyotype is normal and no fetal structural
      malformation was missed prenatally following resolution of nuchal thickening, the
      prognosis is not impaired at the age of 2.

PMID- 17521949
TI  - [Preimplantation diagnosis: ethical reflections].

PMID- 17521950
TI  - Young onset Hemifacial Spasm in patients with Chiari type I malformation.
AB  - Hemifacial spasm (HFS) resulting from Chiari type I malformation (CIM) is rare.
      We retrospectively evaluated five patients with CIM and HFS among a series of 103
      subjects. The frequency of HFS associated to CIM was of 4.85%. The clinical
      profile did not differ from the classical primary cases except for young-onset
      development of facial spasms in patients with CIM. Three patients were treated
      with BTX-A injections with favorable outcome. Although rare HFS may be associated
      with CIM especially in young subjects with peculiar phenotypic characteristics
      (short neck). Moreover, BTX may be an alternative to posterior fossa
      decompression in selected cases.

PMID- 17521952
TI  - Activation of peroxisome proliferator-activated receptor-gamma protects
      pancreatic beta-cells from cytokine-induced cytotoxicity via NF kappaB pathway.
AB  - Diabetes mellitus is characterized by cytokine-induced insulitis and a deficit in
      beta-cell mass. Ligands for peroxisome proliferator-activated receptor-gamma
      (PPAR-gamma) have been shown to have anti-inflammatory effects in various
      experimental models. We questioned whether activation of endogenous PPAR-gamma by
      either PPAR-gamma ligands or adenoviral-directed overexpression of PPAR-gamma (Ad
      PPAR-gamma) could inhibit cytokine-induced beta-cell death in RINm5F (RIN) cells,
      a rat insulinoma cell line. Treatment of RIN cells with interleukin-1 beta (IL-1
      beta) and interferon-gamma (IFN-gamma) induced beta-cell damage through NF kappaB
      dependent signaling pathways. Activation of PPAR-gamma by PPAR-gamma ligands or
      Ad-PPAR-gamma inhibited IL-1 beta and IFN-gamma-stimulated nuclear translocation
      of the p65 subunit and DNA binding activity. NF kappaB target gene expression and
      their product formation, namely inducible nitric oxide synthase and
      cyclooxygenase-2 were decreased by PPAR-gamma activation, as established by real
      time PCR, Western blots and measurements of NO and PGE(2). The mechanism by which
      PPAR-gamma activation inhibited NF kappaB-dependent cell death signals appeared
      to involve the inhibition of I kappa B alpha degradation, evidenced by inhibition
      of cytokine-induced NF kappaB-dependent signaling events by Ad-I kappaB alpha
      (S32A, S36A), non-degradable I kappaB alpha mutant. I kappaB beta mutant, Ad-I
      kappaB beta (S19A, S23A) was not effective in preventing cytokine toxicity.
      Furthermore, a protective effect of PPAR-gamma ligands was proved by assaying for
      normal insulin secreting capacity in response to glucose in isolated rat
      pancreatic islets. The beta-cell protective function of PPAR-gamma ligands might
      serve to counteract cytokine-induced beta-cell destruction.

PMID- 17521951
TI  - Deleted in liver cancer-1 (DLC-1): a tumor suppressor not just for liver.
AB  - Deleted in liver cancer 1 (DLC-1), as its name implied, was originally isolated
      as a potential tumor suppressor gene often deleted in hepatocellular carcinoma.
      Further studies have indicated that down-expression of DLC-1 either by genomic
      deletion or DNA methylation is associated with a variety of cancer types
      including lung, breast, prostate, kidney, colon, uterus, ovary, and stomach. Re
      expression of DLC-1 in cancer cells regulates the structure of actin cytoskeleton
      and focal adhesions and significantly inhibits cell growth, supporting its role
      as a tumor suppressor. This tumor suppressive function relies on DLC-1's
      RhoGTPase activating protein (RhoGAP) activity and steroidogenic acute regulatory
      (StAR)-related lipid transfer (START) domain, as well as its focal adhesion
      localization, which is recruited by the Src Homology 2 (SH2) domains of tensins
      in a phosphotyrosine-independent fashion. Therefore, the expression and
      subcellular localization of DLC-1 could be a useful molecular marker for cancer
      prognosis, whereas DLC-1 and its downstream signaling molecules might be
      therapeutic targets for the treatment of cancer.

PMID- 17521953
TI  - Insulin-like growth factor-II regulates the 12-lipoxygenase gene expression and
      promotes cell proliferation in human keratinocytes via the extracellular
      regulatory kinase and phosphatidylinositol 3-kinase pathways.
AB  - To study the relationship between insulin-like growth factor-II (IGF-II) and 12
      lipoxygenase (12-LOX) that are upregulated in psoriasis, we monitored 12
      lipoxygenase expression in the insulin-like growth factor-II treated human
      keratinocytes and explored the signaling pathways of 12-lipoxygenase expression.
      Insulin-like growth factor-II induced 12-lipoxygenase mRNA and protein levels in
      human keratinocytes through two major signal transduction pathways, namely, the
      extracellular signaling-regulated kinase (ERK)-mitogen activated protein kinase
      (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. The IGF-II-induced
      upregulation of 12-lipoxygenase was attenuated by pretreating the cells with
      selective inhibitors or by overexpressing dominant-negative MEK. In addition,
      treatment of HaCaT cells with the 12-lipoxygenase metabolite 12 (S)
      hydroxyeicosatetraenoic acid (12(S)-HETE) directly stimulated DNA synthesis and
      mitogenesis, and injection of insulin-like growth factor-II into the skin of
      hairless mice induced epidermal hyperplasia. These results suggest that insulin
      like growth factor-II is involved in the pathogenesis of psoriasis as a paracrine
      inducer of 12-lipoxygenase.

PMID- 17521955
TI  - Schistosoma mekongi and Schistosoma japonicum: Differences in the distribution of
      eggs in the viscera of mice.
AB  - The difference in the distribution of Schistosoma eggs in the viscera has not
      been clearly elucidated in the two closely related species Schistosoma japonicum
      and Schistosoma mekongi. In this study, we quantitatively compared the
      distribution of eggs in mice infected with the two species. In S. mekongi
      infected mice, 56.6% to 69.4% of total eggs were found in the distal small
      intestine 9 to 15 weeks after infection, while in S. japonicum-infected mice,
      48.8% to 71.8% of eggs were found in the proximal small intestine during the same
      period. There were significantly more eggs in the liver in mice infected with S.
      japonicum than in those infected with S. mekongi. The number of adult worms
      recovered did not differ between the two species during the study period. The
      total number of eggs laid in the tissues also did not differ between the two
      species at 12 to 15 weeks postinfection, but in the earlier period the total
      number of eggs was significantly fewer in S. mekongi-infected than in S.
      japonicum-infected mice, suggesting the delayed maturation of the former compared
      with the latter. These results clearly show that S. japonicum and S. mekongi
      exhibit different oviposition behavior in their hosts.

PMID- 17521954
TI  - Regulation of cell junction dynamics by cytokines in the testis: a molecular and
      biochemical perspective.
AB  - Studies in the past decade in the field have demonstrated the significance of
      cytokines in regulating epithelial and endothelial cell junctions including tight
      and anchoring junctions in multiple organs including the testis. There are
      mounting evidences in recent years that cytokines play a crucial role in the
      restructuring of junctions at the Sertoli-Sertoli and Sertoli-germ cell interface
      in the seminiferous epithelium during spermatogenesis. These earlier studies,
      however, were focused on the effects of cytokines in maintaining the steady-state
      protein levels of integral membrane proteins at the sites of the blood-testis
      barrier (BTB) and anchoring junctions at the Sertoli-Sertoli and Sertoli-germ
      cell interface, such as basal and apical ectoplasmic specialization,
      respectively. The molecular pathway(s) and/or mechanism(s) underlying these
      effects remained virtually unexplored until very recently. Herein, we summarize
      and provide some discussions on studies that focused on the role of cytokines in
      regulating junction restructuring events in epithelia from a molecular and
      biochemical perspective. Specifically, we use the adult rat or mouse testis as a
      model to highlight the significance of transcriptional and translational
      regulation. Specific areas of research that require further attentions are also
      highlighted.

PMID- 17521956
TI  - Fe3+ concentration dependence of photoacoustic absorption spectroscopy on ZnGa2O4
      ceramic powders.
AB  - In this paper we present the photoacoustic spectroscopy of ZnGa2O4 with 5 and 10%
      of Fe3+. The ZnGa2O4 is a normal spinel, with Zn2+ ions in tetrahedral sites and
      Ga3+ ions in octahedral sites. It is expected for these hosts that Fe3+ ions
      occupy Ga3+ sites. Therefore, the optical properties would be associated to an
      octahedral symmetry. The energy levels were identified and the crystal field and
      electronic interaction parameters calculated with Tanabe-Sugano matrices for d5
      configuration. We have also studied the dependence of the photoacoustic signal
      amplitude on the excitation light modulation frequency. Our results indicate that
      thermal expansion is the predominant phenomenon for the photoacoustic signal
      generation.

PMID- 17521957
TI  - Spectra and structure of binary azeotropes V-acetone-cyclopentane.
AB  - Acetone and cyclopentane make a minimum boiling homogeneous binary azeotrope with
      mole ratio 2:3. Some characteristic vibrational modes, as well as (1)H NMR
      signals change due to the azeotrope formation. The extend of interaction of these
      molecules causes significant changes on some vibrational modes involved and (1)H
      NMR signals show some changes on their position. In this work the FTIR and (1)H
      NMR spectra of pure acetone, pure cyclopentane and corresponding azeotrope were
      recorded, mutual influences resulting from azeotrope formation have been
      analyzed, and spectral changes has been discussed. The unit-structure of cluster
      have been deduced, based on mole ratio, boiling point depression of constituents,
      and comparison between the spectra obtained by FTIR and (1)H NMR techniques.

PMID- 17521958
TI  - Synthesis and characterization of some pyrimidine, purine, amino acid and mixed
      ligand complexes.
AB  - Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes of barbital,
      thiouracil, adenine, amino acids (methionine, lysine and alanine) and some mixed
      ligands were prepared and characterized by elemental analyses, IR, electronic
      spectra, magnetic susceptibility and ESR spectra. Coordination of the metallic
      centre to the oxygen and nitrogen atoms of barbital, thiouracil, amino acids and
      coordinate to amino group and nitrogen atom of adenine occurred. Electronic
      spectra and magnetic susceptibility measurements were utilized to infer the
      structure of the complexes which are octahedral for Mn(II), Fe(III), Co(II),
      Ni(II) and Cd(II) and tetrahedral for Mn(II), Cu(II), Zn(II) complexes. ESR
      spectra were observed for copper complexes with a d(x2)-(y2) ground state with
      small g(||) values indicating strong interaction between the ligands and their
      metal ions.

PMID- 17521959
TI  - Characterization of thalidomide using Raman spectroscopy.
AB  - Thalidomide is a potent anticancer therapeutic drug whose mechanism of action has
      not yet been elucidated. In this report, experimental Raman spectroscopy is used
      to determine and characterize the vibrational frequencies of the drug. These
      normal modes are then compared to their quantum mechanical counterparts, which
      have been computed using density functional theory. Upon analysis of the spectra,
      we found that there was a high level of agreement between the wavenumbers. As
      such, this spectroscopic technique may be a viable tool for examining the way in
      which this drug interacts with its target molecules.

PMID- 17521960
TI  - Evaluation of immunoglobulin M and G capture enzyme-linked immunosorbent assay
      Panbio kits for diagnostic dengue infections.
AB  - BACKGROUND: Serological assays are widely used to confirm dengue virus infections
      and to differentiate between a primary and a secondary infection. OBJECTIVE: Two
      commercial dengue diagnostic kits, Panbio Dengue IgM Capture and Dengue IgG
      Capture ELISA (Brisbane, Australia) were evaluated. STUDY DESIGN: Three hundred
      and seventy-three serum samples were tested. Panel sera included samples from
      dengue confirmed cases (representing both primary and secondary infections), from
      non-dengue infectious diseases, and from healthy individuals. The MAC
      ELISA/Dengue IPK was used for the detection of anti-dengue virus IgM antibody in
      the sera and the ELISA inhibition method (EIM/Dengue IPK) was used to
      differentiate between primary and secondary infections. Both these reference
      assays, which were previously developed in the Arbovirus Laboratory at the "Pedro
      Kouri" Tropical Medicine Institute, were employed as the gold standard. RESULTS:
      High sensitivity (96.8%) and specificity (99.4%) were found with the commercial
      diagnostics when compared to the reference methods. Furthermore, high concordance
      95.5% in classifying dengue infection types (primary or secondary infections) was
      observed. CONCLUSIONS: The Panbio Dengue IgM and IgG assays offer a good
      alternative for dengue diagnosis. They are easy to perform and results can be
      obtained in less than 3h.

PMID- 17521961
TI  - Ganglioside GM(3) is stably associated to tyrosine-phosphorylated ErbB2/EGFR
      receptor complexes and EGFR monomers, but not to ErbB2.
AB  - Gangliosides are known to modulate the activation of receptor tyrosine-kinases
      (RTKs). Recently, we demonstrated the functional relationship between ErbB2 and
      ganglioside GM(3) in HC11 epithelial cell line. In the present study we
      investigated, in the same cells, the ErbB2 activation state and its tendency to
      form stable molecular complexes with the epidermal growth factor receptor (EGFR)
      and with ganglioside GM(3) upon EGF stimulation. Results from co
      immunoprecipitation experiments and western blot analyses indicate that tyrosine
      phosphorylated ErbB2 and EGFR monomers and stable ErbB2/EGFR high molecular
      complexes (heterodimers) are formed following EGF stimulation, even if the
      receptors co-immunoprecipitates also in the absence of the ligand; these data
      suggest the existence of pre-dimerization inactive receptor clusters on the cell
      surface. High performance-thin layer chromatography (HP-TLC) and TLC
      immunostaining analyses of the ganglioside fractions extracted from the
      immunoprecipitates demonstrate that GM(3), but not other gangliosides, is tightly
      associated to the tyrosine-phosphorylated receptors. Furthermore, we show that
      GM(3) is preferentially and in a SDS-resistant manner associated to the activated
      ErbB2/EGFR complexes and EGFR monomer, but not to ErbB2. Altogether our data
      support the hypothesis that the modulating effects produced by GM(3) on ErbB2
      activation are mediated by EGFR.

PMID- 17521962
TI  - Functional T cell subsets contribute differentially to HIV peptide-specific
      responses within infected individuals: correlation of these functional T cell
      subsets with markers of disease progression.
AB  - Using a dual color ELISPOT assay able to detect HIV-specific IFN-gamma, IL-2 and
      dual IFN-gamma/IL-2 secreting lymphocytes we screened for HIV peptide-specific
      responses directed against the entire HIV proteome in two groups of untreated HIV
      infected individuals, slow progressors (SP) and progressors. We found that the
      three functional lymphocyte subsets contributed differentially to individual HIV
      peptide-specific responses within a study subject. Among the identified
      stimulatory peptides, a higher proportion induced dual IFN-gamma/IL-2 secretion
      in SP than progressors. While the magnitude of single IFN-gamma secreting
      lymphocytes is similar between groups, the magnitude of peptide-specific dual IFN
      gamma/IL-2 secreting lymphocytes is significantly more intense in SP. Neither
      single nor total IFN-gamma secreting cell magnitude and breadth measurements
      correlated with CD4 cell count or viral load whereas both parameters of dual IFN
      gamma/IL-2 secreting responses correlated positively with CD4 counts and
      negatively with viremia.

PMID- 17521964
TI  - Interactions between seizure frequency, psychopathology, and severity of
      intellectual disability in a population with epilepsy and a learning disability.
AB  - Despite observations associating lower IQ and psychopathology in epilepsy, the
      possible differential effects of varying severity of learning (intellectual)
      disability (LD) on the manifestation of psychopathology in people with LD and
      epilepsy have not been clarified. In this study of retrospectively collected data
      describing the epilepsy, learning disability, and psychopathology of 175 patients
      with epilepsy and LD over a 3-month period, we observed that 65 patients had no
      recent seizures, whereas 110 had experienced at least one seizure in the
      preceding 3 months. We found that depression and psychoses were more common in
      those with no seizures in the preceding 3 months, but that which of these
      psychiatric states was manifest was related to the severity of LD. Psychosis
      rates were higher in those with mild LD, whereas depression rates were higher in
      those with severe LD.

PMID- 17521963
TI  - Association between ABCB1 C3435T polymorphism and drug-resistant epilepsy in Han
      Chinese.
AB  - There is accumulating evidence to suggest that overexpression of efflux drug
      transporters at the blood-brain barrier, by reducing antiepileptic drug (AED)
      accumulation in the seizure foci, contributes to drug resistance in epilepsy. P
      glycoprotein, encoded by the ABCB1 gene, is the most studied drug transporter.
      There are conflicting data as to whether the CC genotype of the ABCB1 3435C>T
      polymorphism is associated with drug resistance in Caucasian patients with
      epilepsy. We investigated this association in ethnic Chinese. ABCB1 3435C>T was
      genotyped in 746 Han Chinese patients with epilepsy and 179 controls. Patients
      with drug-resistant epilepsy were more likely to have the TT genotype compared
      with those with drug-responsive epilepsy (16.7% vs 7.4%, odds ratio=2.5, 95%
      confidence interval=1.4-4.6, P=0.0009). Our results contrast with those of
      studies of Caucasians, and highlight the complexity of the possible role of this
      polymorphism in AED response in different ethnic populations.

PMID- 17521965
TI  - Epileptiform EEG discharges in benign childhood epilepsy with centrotemporal
      spikes: reactivity and transitory cognitive impairment.
AB  - The reactivity of rolandic spikes (RS) and the occurrence of transitory cognitive
      impairment (TCI) during RSs were assessed in 33 children with benign childhood
      epilepsy with centrotemporal spikes (BECTS). The children were assessed
      simultaneously with EEG and computerized neuropsychological testing in a visual
      discrimination between words and pseudowords task (DWPT). In 20 (60.6%) children,
      there were insufficient RS to assess the occurrence of TCI. Of 13 children with
      RS between stimulus presentation and response, only 2 (15.4%) made a
      significantly greater proportion of errors during RS than during RS-free periods,
      characterizing the occurrence of TCI. The RS appear to be easily inhibited by the
      DWPT. TCI occurred in a limited number of cases and did not impair school
      performance. There is a need to study other tasks and search for other factors
      influencing cognitive abilities in children with BECTS.

PMID- 17521966
TI  - rh-BMP-2 can be used safely in the cervical spine: dose and containment are the
      keys!

PMID- 17521967
TI  - Changes in stretch-induced tone induced by intracellular acidosis in rabbit
      basilar artery: effects on BKCa channel activity.
AB  - It is known that myogenic reactivity is a fundamental determinant of the relative
      constancy of blood flow through the cerebral artery. It is also known that acute
      alteration of pH significantly affects the cerebral circulation and, therefore,
      we investigated the effect of mechanism of action of intracellular acidosis on
      myogenic tone in rabbit basilar artery. Myogenic tone was developed by imposed
      stretch of basilar artery and intracellular acidosis induced by the bath
      application of 20 mmol/L sodium acetate. Sodium acetate caused a biphasic
      increase in myogenic tone. The initial component reached a peak quickly and then
      fell slowly to a lower steady-state significantly above basal tone. The sodium
      acetate-induced increase in myogenic tone was completely inhibited by elimination
      of external Ca2+, or treatment of nifedipine, but not with gadolinium or NPPB.
      TEA (5 mmol/L) and iberiotoxin (100 nmol/L) inhibited the sodium acetate-induced
      increase in myogenic tone. In inside-out patch-clamp recordings, decreasing pH of
      the mock intracellular solution from 7.4 to 6.9 markedly inhibited BKCa currents.
      Several inhibitors involved in Ca2+ sensitization pathways, 10(-6) mol/L Y-27632,
      5 x 10(-7) mol/L calphostin C and 10(-5) mol/L PD98059 had no effect on the
      sodium acetate-induced increase in myogenic tone. These results suggest that
      intracellular acidosis increases stretch-induced myogenic tone in rabbit basilar
      artery. Furthermore, voltage-dependent Ca2+ influx plays a key role in
      intracellular acidosis-induced increase in myogenic tone and may be mediated, at
      least in part, by inhibition of BKCa.

PMID- 17521968
TI  - AT1 receptor antisense therapy transiently lowers blood pressure in Ren-2
      transgenic rats.
AB  - The effectiveness of antisense (AS) phosphorothioated oligodeoxynucleotides (AS
      ODN) targeted to the angiotensin (ANG) type 1 (AT1) receptor, was studies in Ren
      2 transgenic rats (TGR), whose ANG II-dependent hypertension can be attributed to
      the insertion of a single mouse renin gene. Our results show that a single
      intraarterial bolus injection of AT1-AS in 30-day-old rats results in a prolonged
      lowering of systolic blood pressure (SBP) for a period of 18 days with an average
      difference in SBP of 30 mm Hg between AS-treated and untreated TGR. No effect of
      AS therapy on SBP has been observed in control HanSD animals. However, at the end
      of the experiment, i.e. on day 100 of age, there were no differences in mean
      arterial pressure, proteinuria or cardiac hypertrophy between AS-treated and
      untreated TGR. Thus, no persistent effect of this therapy was observed after a
      single bolus injection. Collectively, the data show a prolonged antihypertensive
      effect of AT1 receptor antisense oligonucleotides during the developmental phase
      of hypertension in TGR when applied as a single treatment in prehypertensive
      animals which, however, does not persist up to the maintenance phase of
      hypertension in adulthood.

PMID- 17521969
TI  - Expression and regulation of the zinc finger transcription factor Churchill
      during zebrafish development.
AB  - During gastrulation dynamic cell movements establish the germ layers and shape
      the body axis of the vertebrate embryo. The zinc finger protein Churchill (chch)
      has been proposed to be a key regulator of these movements. We examined the
      expression pattern of chch in zebrafish and studied the regulation of chch by FGF
      signaling. We observed zygotic expression of chch during early cleavage stages.
      Two lines of evidence demonstrate that chch is zygotically expressed prior to the
      mid-blastula transition. First, blocking transcription during early cleavage
      stages represses chch expression. Second, endogenous levels of chch transcripts
      increase between 1-cell and 16-cell embryos. chch remains widely expressed during
      blastula and gastrula stages but scattered cells express higher levels of chch.
      By somitogenesis, chch is expressed in the ventral-most cells of the embryo
      adjacent to the yolk. In addition, transcripts are also observed in superficial
      cells on the surface of the yolk, in presumptive mucous cells and keratinocytes.
      By 30 hpf transcripts are observed in anterior neural tissue and ventral cells
      adjacent to the yolk. Over the next three days chch expression is indistinct
      until 4 dpf when we observe expression in the pharynx and gut. We show that
      activation of FGF signaling during gastrulation is sufficient to induce chch
      expression. In addition, we demonstrate that blocking FGF signaling between the 4
      cell and shield stages represses chch expression.

PMID- 17521970
TI  - Aggregation in malaria parasites places limits on mosquito infection rates.
AB  - Gametocytes are responsible for the transmission of malaria parasites, Plasmodium
      spp., from man to mosquito. Although transmission success, as measured by the
      proportion of mosquitoes infected, generally increases with gametocyte density,
      the proportion of parasites that are gametocytes is always paradoxically only a
      few percent of the asexual blood parasites. To address this paradox, we analyse
      transmission data sets from an urban and an adjacent rural setting in Cameroon to
      elucidate whether there are discernable lower and upper limits to Plasmodium
      falciparum gametocyte density that are linked to transmission success. We find
      that there exists a lower gametocyte density at which mosquito infection rates
      considerably increase. In addition, we identify upper gametocyte densities at
      which mosquito infection rates level off. Greatest increases in infection rates
      occur at low gametocyte densities and coincide with maximum oocyst aggregation
      within the infected mosquito population. This aggregated oocyst distribution
      remains despite increases in gametocyte density and ever-decreasing gains in
      mosquito infection rates. There is increasing suggestion that malaria parasites
      have evolved sex allocation strategies to ensure transmission in response to a
      changing, transmission-blocking environment. Here transmission-blocking immunity
      is proposed not only to ensure low density gametocyte transmission success but
      also to impose upper limits on transmission success.

PMID- 17521971
TI  - Exercise and hypoxia: the role of the autonomic nervous system.
AB  - The reduction in maximal oxygen consumption in hypoxia can be due to
      physiological factors, the relative importance of which depends on the degree of
      hypoxia: the reduction in inspired PO2, the impairment of lung gas exchange
      contributing to an exercise-induced decrease in arterial O(2) saturation, the
      reduction in maximal cardiac output and the limitation in tissue diffusion. This
      paper focuses on two aspects of this oxygen cascade. First, the decrease in heart
      rate at maximal exercise in prolonged exposure to hypoxia is discussed and the
      role of changes in the autonomous nervous system is emphasised. The
      desensitization of the beta-adrenergic pathway and the upregulation of the
      muscarinic pathway, both using G-protein systems, contribute to limit the
      myocardial O(2) consumption in face of reduced O(2) availability during maximal
      exercise in hypoxia. The changes in O(2) diffusion to the tissues are discussed
      in relation to the expression of hypoxia inducible factor (HIF-1alpha) and
      vascular endothelial growth factor (VEGF) and their possible changes induced by
      training and/or hypoxic exposure.

PMID- 17521972
TI  - Determination of ellagic acid in oak leaves and in sheep ruminal fluid by ion
      pair RP-HPLC.
AB  - An isocratic ion-pair high-performance liquid chromatography (IP-RP-HPLC) method
      with UV detection was developed to identify and quantify ellagic acid (EA). This
      phenolic compound is widely distributed in the plants and is often present in the
      diet of ruminants. The method was validated and validation parameters were:
      linearity range 5-100 mg/L; correlation coefficient, 0.9995; mean recoveries
      (99.94 and 101.07%) and detection limit 1.4 mg/L. Method was applied for the
      determination of ellagic acid in oak leaves and in ruminal fluid from to a vitro
      ruminal system. The proposed method proved to be rapid and accurate and can be
      successfully used in ruminant nutrition studies.

PMID- 17521973
TI  - Determination of propylthiouracil and methylthiouracil in human serum using high
      performance liquid chromatography with chemiluminescence detection.
AB  - Based on the sensitizing effect of formaldehyde on the chemiluminescence (CL)
      reaction of propylthiouracil (PTU) and methylthiouracil (MTU) with acidic
      potassium permanganate and the combination technique of high-performance liquid
      chromatography (HPLC), a sensitive, selective and simple post-column CL detection
      method for determining PTU and MTU is described. The optimal conditions for the
      CL detection and HPLC separation were carried out. The linear ranges were 0.1-20
      microg mL(-1) for MTU and 0.1-10 microg mL(-1) for PTU, the detection limits were
      0.03 microg mL(-1) for PTU, 0.03 microg mL(-1) for MTU and the quantification
      limits were 0.1 microg mL(-1) for PTU, 0.1 microg mL(-1) for MTU. The method has
      been satisfactorily applied for the determination of MTU and PTU in human serum
      samples.

PMID- 17521974
TI  - An integrated analysis of the effects of Esculentin 1-21 on Saccharomyces
      cerevisiae.
AB  - The antimicrobial peptide esculentin 1-21 (Esc 1-21) is a shorter synthetic
      version of the 46-residue peptide occurring in the Rana esculenta skin secretion.
      Here we propose an integrated proteomic and transcriptomic approach to interpret
      the biological effects of this peptide on Saccharomyces cerevisiae. We further
      investigated the response to this peptide by correlating the results of the
      transcriptome and proteome analysis with phenotypic effects. The results show
      that S. cerevisiae adapts to Esc 1-21 using the High Osmolarity Glycerol (HOG)
      pathway involved in osmotic tolerance and cell wall maintenance. Comparative
      proteomics reveals that Esc 1-21 causes downregulation of enzymes of the lower
      glycolytic pathway and in genes involved in spindle body formation and
      remodelling of cell-wall synthesis. Moreover the peptide induces downexpression
      of protein actin within 45 min and cells pre-treated with peptide show less
      sensitivity to osmotic stress and increased sensitivity to heat shock stress. The
      results obtained with the two different methodologies are in agreement at the
      cellular process levels. A combined approach may help elucidate the main aspects
      related to the effects of this peptide on the eukaryotic cell. The employment of
      different technologies may reveal the potential and limitations of each adapted
      approach in a prospective application for drug screening.

PMID- 17521975
TI  - Meralgia paresthetica: a result of tight new trendy low cut trousers ('taille
      basse').
AB  - Meralgia paresthetica is an entrapment neuropathy involving the lateral femoral
      cutaneous nerve of the thigh. Patients complain of a persistent burning
      sensation, tingling and aching pain, and hypersensitivity or hyposensitivity in
      the anterolateral aspect of the thigh. Numerous direct and indirect causes for
      the disease have been suggested in the literature. We present 12 cases that were
      diagnosed to have meralgia paresthetica due to tight new fashion low cut trousers
      ('taille basse'). The diagnosis was confirmed by injecting a small amount of a
      short acting local anesthetic around the lateral femoral cutaneous nerve which
      alleviated the symptoms for several hours. Electrophysiologic studies were
      sensitive in 83.3% of the cases. All cases were treated successfully using
      conservative methods, namely avoiding tight trousers, local steroid infiltration
      and weight reduction.

PMID- 17521976
TI  - Hand and microvascular surgery: a serious business.

PMID- 17521977
TI  - Actualities in big segments replantation surgery.
AB  - Replantation of an amputation is no longer a difficult technical problem. Indeed,
      the experience gathered over the last few decades, right from the first concepts
      posed by the pioneers up to the present era and the improved technical aids, all
      go to suggest that the majority of amputated segments may now be reconstructed.
      However, what we really want from a replant is not just survival but function.
      Indications for replantations must follow careful and objective patient selection
      together with the evaluation of type and site of lesion and possible
      complications. Furthermore, the important role of emergency organization in this
      type of surgery is to be emphasized. Nowadays, clean cut injuries are rarer and
      are being substituted by high energy trauma which may produce extensive tissue
      lesions that increase complications and lead to poor functional results.
      Consequently, some authors were induced to describe evaluation systems for
      decision making which still present problems which are in part due to the large
      number of parameters to be taken into consideration as well as to the complex
      functionality of the upper limb. This led us to evaluate our case series of 52
      major replantations of the upper limb over the last 10 years and to compare it
      with other published series. The best form of reconstruction following total
      amputation of a major limb segment is still its replantation. The highly
      significant increase in the quality of life is able to justify the higher social
      costs and the number of operations required.

PMID- 17521978
TI  - A new Chinese specimen indicates that 'protofeathers' in the Early Cretaceous
      theropod dinosaur Sinosauropteryx are degraded collagen fibres.
AB  - Alleged primitive feathers or protofeathers in the theropod dinosaur
      Sinosauropteryx have potentially profound implications concerning feather
      morphogenesis, evolution offlight, dinosaur physiology and perhaps even the
      origin of birds, yet their existence has never been adequately documented. We
      report on a new specimen of Sinosauropteryx which shows that the integumental
      structures proposed as protofeathers are the remains of structural fibres that
      provide toughness. The preservation in the proximal tail area reveals an
      architecture of closely associated bands offibres parallel to the tail's long
      axis, which originate from the skin. In adjacent more exposed areas, the fibres
      are short, fragmented and disorganized. Fibres preserved dorsal to the neck and
      back and in the distal part of the tail are the remains of a stiffening system of
      a frill, peripheral to the body and extending from the head to the tip of the
      tail. These findings are confirmed in the holotype Sinosauropteryx and NIGP
      127587. The fibres show a striking similarity to the structure and levels of
      organization of dermal collagen. The proposal that these fibres are protofeathers
      is dismissed.

PMID- 17521979
TI  - Introduction:social work and the development of a more compassionate world:
      experiences and knowledge to share.

PMID- 17521980
TI  - The Fourth International Conference on Social Work in Health and Mental Health:
      welcoming remarks.

PMID- 17521981
TI  - Compassion and solidarity.

PMID- 17521982
TI  - Ethical preferences for the clinical practice of empowerment social work.
AB  - Social workers in health care and mental health benefit from interventions that
      integrate principles of contextual social work practice with standards for
      clinical practice. The authors articulate a conceptual framework for the ethical
      practice of social work that complements the social justice purpose. The sixteen
      ethical preferences in this framework are the ethics of care, autonomy, power,
      change, respect, critical thinking, praxis, discourse, critique, justice,
      contextual practice, inclusion, anti-oppression, advocacy, collaboration, and
      politicized practice.

PMID- 17521983
TI  - Cultural competence in HIV prevention and care: different histories, shared
      future.
AB  - The importance of cultural competence in social work practice is becoming
      increasingly more evident as the dividing lines between countries and cultures
      continue to fade away. Successful practice in today's global environment hinges
      on the ability to accept differences and to work towards a shared future. The
      necessity of cultural competence is painfully obvious when considering HIV
      prevention and care. From the start, HIV has been a global epidemic that has
      devastated many regions of world. The current paper examines the issue of HIV
      care and prevention from the perspective of Indonesia and the United States.
      Juxtaposition of these two countries reveals that they have approached HIV care
      and prevention differently because of their different histories. However, it is
      advanced that the two countries are likely to have a shared future given the
      highest infection rates are locating in similar populations, i.e., sex trade
      workers, intravenous drug users, street children-generally the poor, the
      oppressed, and their partners. Culturally competent social workers can play an
      important role in the fight against HIV by understanding and adapting to cultural
      differences and by merging best practices.

PMID- 17521984
TI  - We care don't we? Social workers, the profession and HIV/AIDS.
AB  - The HIV/AIDS epidemic has impacted all levels of society from the individual to
      the macro-economic. The continuing spread of infection around the world means
      that traditional methods of care and support are put under extreme pressure and
      many families lose their capacity to cope. Social workers are involved in
      providing care, counseling and support to those affected, and in developing
      programmes and other interventions to prevent the spread of the disease.
      Prevention and behaviour change are vital, but access to treatment is an ethical
      imperative, particularly in developing countries where the epidemic is most
      prevalent. Social work is a profession uniquely situated to demonstrate
      leadership in multi-sectoral collaboration in responding to this pandemic.
      Consequently this paper briefly reviews the scale and current nature of the
      epidemic and then considers how social workers can help build more compassionate
      policies at an international level. Social workers can help to create awareness
      of the negative effects of poverty, tackle gender inequity, help build more
      effective coalitions and partnerships, and work with other concerned groups and
      organisations to end stigma and discrimination. Using case examples the paper
      considers how social workers can help develop caring strategies that improve the
      lives of those living with HIV and AIDS.

PMID- 17521985
TI  - An investigation of the practice of unsafe sex yet repeated HIV testing.
AB  - RATIONALE: A purportedly heterogeneous group of people, who come to take tests at
      the Human Immunodeficiency Virus (HIV) Test-ing Clinic, includes young males and
      females who lead a normative lifestyle with no unique characteristics. Within
      this population, we have observed one distinct subgroup of predominantly male
      individuals, who return from time to time to take the HIV tests. They tend to
      partake in many occasional sexual encounters with numerous partners, and despite
      their obvious knowledge of the risks involved, they attest to not using condoms
      during sexual intercourse. The aim of this preliminary study was to investigate
      the patterns of their risky behavior in conjunction with their test taking
      conduct. METHODS: Ten self-referred volunteering subjects were recruited.
      EXCLUSION CRITERIA: HIV-positive, drug and/or alcohol abusers, mentally ill, men
      who have sex with men (MSM) and minors. The study was carried-out using semi
      structured interviews (40-90 min each). The interviews were recorded, transcribed
      and content analyzed. FINDINGS: Data analysis showed several possible
      explanations for risky sexual behavior, such as applying of a variety of risk
      management mechanisms, refraining from impulse control behaviors, and self
      destruction motives. The reasons for undergoing HIV testing were most frequently
      related to specific events, high-risk in nature, and not part of a routine
      behavioral practice. CONCLUSIONS: Our findings might suggest that within this
      population group, the prevailing primary preventive interventions would not
      satisfy the purpose of decreasing levels and frequency of risk-taking behaviors.
      In the opinion of the authors, there are two strategies that could be employed,
      simultaneously or separately. An indirect approach entails the increase and
      enhancement in utilizing widely spread media, e.g., feature films and television
      programs, to convey issues related to curbing risk-behavior. Direct emphasis
      should be put on secondary preventive measures, by encouraging frequent test
      taking conduct, preferably accompanied by counseling, in order to decrease the
      risk of further transmitting the virus.

PMID- 17521986
TI  - Promoting the psychosocial health of the elderly- the role of social workers.
AB  - With the ageing of the global population, the wellbeing of older people in
      different parts of the world merits special attention. However, recent findings
      on certain aspects of the psychosocial health of the elderly are far from
      reassuring. The first problem is the inconsistency in psychosocial indicators,
      which give simultaneous high life satisfaction scores and high suicide rates. The
      second problem is the significant weakening of the social support network of the
      elderly. This article analyses the service and policy implications of these two
      problems. Suggestions are then made on the role of social workers in promoting
      the psychosocial health of the elderly at different levels of intervention, which
      include the individual level, the family and social network level, the community
      level and the international level.

PMID- 17521987
TI  - Promoting older people's voices- the contribution of social work to inter
      disciplinary research.
AB  - UK government policies over the last decade or more have focussed on giving older
      people more voice in the design, delivery and assessment of services. Mirroring
      these trends, there has been a shift towards increased involvement of older
      people in the research process. Drawing on three research studies, this paper
      examines the contribution of social work to an inter-disciplinary research agenda
      designed to promote increased involvement of older people in issues of service
      quality in primarily health settings. Challenges and opportunities are discussed.
      Each of the studies illustrates the importance of promoting research practice
      congruent with social work's commitment to partnership and empowering forms of
      practice. This, it is argued, requires the challenging of ageist assumptions, the
      use of a range of research methods and the valuing of different forms of
      knowledge.

PMID- 17521988
TI  - IntroductionExposing Misinformation Concerning Child Sexual Abuse and Adult
      Survivors.
AB  - This article introduces a special volume on misinformation about child sexual
      abuse. Despite extensive research findings on the long-term effects and
      consequences of child sexual abuse, misinformation on this topic is widespread.
      Several forces have worked to support and disseminate this erroneous information.
      Because it is difficult to comprehend the horror of sexual crimes against
      children, society's denial and disbelief have often unwittingly supported the
      agendas of those who want to discount or minimize the impact of these crimes. The
      media has also contributed to the aura of skepticism surrounding claims of sexual
      abuse and its mental health impact, and has reported favorably on controversial
      and unproven claims such as the &#0147;false memory syndrome.&#0148; In the hope
      of countering misinformation and thus raising the level of discourse to the
      engagement of real scientific issues, a number of well known and respected
      researchers and clinicians examine various facets of the problem.

PMID- 17521989
TI  - Crisis or creation?a systematic examination of "false memory syndrome".
AB  - In 1992, the False Memory Syndrome Foundation (FMSF), an advocacy organization
      for people claiming to be falsely accused of sexual abuse, announced the
      discovery of a new syndrome involving iatrogenically created false memories of
      childhood sexual abuse. This article critically examines the assumptions
      underlying &#0147;False Memory Syndrome&#0148; to determine whether there is
      sufficient empirical evidence to support it as a valid diagnostic construct.
      Epidemiological evidence is also examined to determine whether there is data to
      support its advocates' claim of a public health crisis or epidemic. A review of
      the relevant literature demonstrates that the existence of such a syndrome lacks
      general acceptance in the mental health field, and that the construct is based on
      a series of faulty assumptions, many of which have been scientifically disproven.
      There is a similar lack of empirical validation for claims of a &#0147;false
      memory&#0148; epidemic. It is concluded that in the absence of any substantive
      scientific support, &#0147;False Memory Syndrome&#0148; is best characterized as
      a pseudoscientific syndrome that was developed to defend against claims of child
      abuse.

PMID- 17521990
TI  - The legend of robert halsey.
AB  - This article examines the criminal conviction of Robert Halsey for sexually
      abusing two young boys on his school-van route near Pittsfield, Massachusetts.
      Mr. Halsey's name has been invoked by academics, journalists, and activists as
      the victim of the &#0147;witch hunt&#0148; in this country over child sexual
      abuse. Based on a comprehensive examination of the trial transcript, this article
      details the overwhelming evidence of guilt against Mr. Halsey. The credulous
      acceptance of the &#0147;false conviction&#0148; legend about Robert Halsey
      provides a case study in the techniques and tactics used to minimize and deny
      sexual abuse, while promoting a narrative about &#0147;ritual abuse&#0148; and
      &#0147;witch hunts&#0148; that apparently requires little or no factual basis.
      The second part of this article analyzes how the erroneous &#0147;false
      conviction&#0148; narrative about Robert Halsey was constructed and how it gained
      widespread acceptance. The Legend of Robert Halsey provides a cautionary tale
      about how easy it is to wrap even the guiltiest person in a cloak of righteous
      &#0147;witch hunt&#0148; claims. Cases identified as &#0147;false
      convictions&#0148; by defense lawyers and political activists deserve far greater
      scrutiny from the media and the public.

PMID- 17521991
TI  - The "False Memory" DefenseUsing Disinformation and Junk Science In and Out of
      Court.
AB  - This article describes a seemingly sophisticated, but mostly contrived and often
      erroneous &#0147;false memory&#0148; defense, and compares it in a brief review
      to what the science says about the effect of trauma on memory. Child sexual abuse
      is widespread and dissociative/traumatic amnesia for it is common. Accused,
      convicted and self-confessed child molesters and their advocates have crafted a
      strategy that tries to negate their abusive, criminal behavior, which we can call
      a &#0147;false memory&#0148; defense. Each of 22 of the more commonly used
      components of this defense is described and discussed with respect to what the
      science says about them. Armed with this knowledge, survivors, their clinicians,
      and their attorneys will be better able to refute this defense of disinformation.

PMID- 17521992
TI  - (Mis) representations of the long-term effects of childhood sexual abuse in the
      courts.
AB  - This study addresses the (mis) representations made by pro-false memory attorneys
      and expert witnesses in court regarding the long-term effects of childhood sexual
      abuse (CSA). Five pro-false memory positions were identified: (1) there is no
      causal connection between CSA and adult psychopathology; (2) the evidence is
      insufficient; (3) CSA does not cause specific trauma-related outcomes like
      borderline and dissociative identity disorder; (4) other variables than CSA
      explain the variance of adult psychopathology; and (5) the long-term effects of
      CSA are general and non-specific. Examining the testimony revealed that such pro
      false memory testimony was based solely on a partial understanding of
      retrospective data and that pro-false memory experts do not cite the more recent
      prospective data. Reviewing the totality of the scientific evidence demonstrates
      that such pro-false memory testimony is inaccurate and has the potential of
      misleading the jury. Prospective studies provide sufficient evidence to causally
      link CSA to a number of areas of adult psychopathology including multiple, co
      morbid psychiatric conditions, and possibly to link early parent-infant
      attachment pathology to the development of borderline and dissociative identity
      disorder.

PMID- 17521993
TI  - Science or propaganda?an examination of rind, tromovitch and bauserman (1998).
AB  - An article, &#0147;A Meta-analytic Examination of Assumed Properties of Child
      Sexual Abuse Using College Samples,&#0148; published in the July 1998 edition of
      the Psychological Bulletin resulted in an unprecedented amount of media attention
      and became the first scientific article to be formally denounced by the United
      States House of Representatives. The study's authors analyzed the findings of 59
      earlier studies on child sexual abuse (CSA) and concluded that mental health
      researchers have greatly overstated CSA's harmful potential. They recommended
      that a willing encounter with positive reactions would no longer be considered to
      be sexual abuse; instead, it would simply be labeled adult-child sex. The study's
      conclusions and recommendations spawned a debate in both the popular and
      scholarly press. A number of commentators suggested that the study is pedophile
      propaganda masquerading as science. Others claimed that the authors are victims
      of a moralistic witch-hunt and that scientific freedom is being threatened. After
      a careful examination of the evidence, it is concluded that Rind et al. can best
      be described as an advocacy article that inappropriately uses science in an
      attempt to legitimize its findings.

PMID- 17521994
TI  - A critical appraisal of the 1998 meta-analytic review of child sexual abuse
      outcomes reported by rind, tromovitch, and bauserman.
AB  - The goal of this article is to present a methodological critique of the 1998 meta
      analysis of child sexual abuse outcomes by Rind, Tromovitch, and Bauserman. Seven
      major concerns are addressed. Rind et al.'s view is, at best, extremely limited.
      By restricting a supposedly broad meta-analysis to only some of the population in
      question, the conclusions they drew regarding this complex topic, primarily that
      adult-child sex is not necessarily harmful, are invalid.

PMID- 17521995
TI  - The Real Controversy About Child Sexual Abuse ResearchContradictory Findings and
      Critical Issues Not Addressed by Rind, Tromovitch, and Bauserman in Their 1998
      Outcomes Meta-Analysis.
AB  - This article presents a review of all types of child sexual abuse research
      ignored by Rind, Tromovitch, and Bauserman in their 1998 meta-analytic study.
      Eight major findings are addressed. Altogether, these findings demonstrate the
      narrow focus of the Rind et al. meta-analysis. By restricting a supposedly broad
      meta-analysis to only some of the research and population in question, the
      conclusions Rind et al. drew regarding this complex topic (primarily, that adult
      child sex is not necessarily harmful to children) are invalid.

PMID- 17521996
TI  - Implications of the Memory Controversy for Clinical PracticeAn Overview of
      Treatment Recommendations and Guidelines.
AB  - The controversy surrounding delayed and recovered memories of incest/child sexual
      abuse has had a profound impact on clinical practice. This article first provides
      an overview of the positions taken by both sides in the dispute, the &#0147;false
      memory&#0148; proponents and the traumatic stress proponents. It then presents
      the major findings of several of the professional task forces charged with
      reviewing the controversy and arriving at recommendations for research, clinical
      practice, and forensic practice regarding delayed recall of memories for sexual
      abuse. The current status of scientific and clinical knowledge is discussed,
      especially in terms of its implications for therapists and clinical practice.
      Nineteen recommendations and practice guidelines are presented for therapists
      working with individuals who report or suspect childhood sexual abuse on the
      basis of continuous and/or recovered memory.

PMID- 17521997
TI  - Including siblings in the treatment of child sexual abuse.
AB  - Siblings are often not included in treatment programs for children who have been
      sexually abused. This article describes the necessity of including siblings in
      the treatment of victims of child sexual abuse. Including siblings in treatment
      permits families to realize the maximum benefits of therapy for the victim as
      well as each family member. Theoretical and practical reasons to include siblings
      in treatment are discussed (i.e., preventing future abuse, providing support for
      siblings, teaching siblings to refrain from victim-blaming). Case examples using
      a particular intervention approach at The Family Learning Program and results of
      client satisfaction surveys are described.

PMID- 17521998
TI  - Issues inherent in the multicultural feminist couple treatment of African
      American, same-gender loving female adult survivors of child sexual abuse.
AB  - This manuscript focuses on four potential stumbling blocks in the multicultural
      feminist couple treatment of African-American, same-gender loving female adult
      child sexual abuse survivors: (1) gender roles; (2) "coming out" to self, family,
      and the community; (3) lesbian couple relationships; and (4) the expression of
      lesbian sexuality. These four potential barriers to therapeutic outcome within
      the context of multicultural feminist couple treatment needs to be systematically
      addressed during the provision of culturally-informed clinical services to
      African-American, same-gender loving female adult child sexual abuse survivors.
      The nature and impact of feminism on the family, as an institution, served as the
      framework for this discussion.

PMID- 17521999
TI  - Helping parents address their child's sexual behavior problems.
AB  - This article describes a model for helping parents address their child's sexually
      inappropriate behavior. The model focuses on: supporting parents and facilitating
      their ability to accept their child's sexual problems, processing their affective
      and cognitive reactions, and devising a plan to help parents talk directly with
      their child about the sexually problematic behavior. Each step of the model
      outlines the rationale and interventions used to accomplish prescribed goals.

PMID- 17522000
TI  - Factors affecting college students' perceptions of sexual relationships between
      high school students and teachers.
AB  - This study explored the effects of respondent gender, gender combination (male
      teacher/female student versus female teacher/male student), and teacher age (24
      versus 39-years-old) on the perception of a sexual relationship between a teacher
      and a 16-year-old student. Participants were 80 male and 80 female
      undergraduates. A MANOVA yielded significant main effects for respondent gender
      and gender combination. Subsequent ANOVAs indicated that men generally viewed the
      experience more positively and that the male teacher/female student combination
      was viewed more negatively than the female teacher/male student pairing.

PMID- 17522001
TI  - Childhood sexual abuse, dissociation, and adult self-destructive behavior.
AB  - Female college students reporting a history of childhood sexual abuse (N=175) and
      not reporting a history of childhood sexual abuse (N=260) were compared on
      indices of six self-destructive behaviors, including drug use, alcohol abuse,
      binge eating, self-mutilation, risky sex, and suicidality. The samples were also
      compared on two measures of dissociation, the Trauma Symptom Checklist
      dissociation subscale and the Dissociative Experiences Scale. The CSA group had
      significantly higher mean scores on all the indices of self-destructive behavior
      except self-mutilation (where the mean difference approached significance), and
      on both measures of dissociation. One or both dissociation measures were related
      significantly to each index of self-destructive behavior except binge eating.
      Multiple regression mediation analyses provided support for the hypothesis that
      dissociation mediates the relationships between CSA and both drug use and alcohol
      abuse. Dissociation also explained significant variability when added to the
      regressions of risky sex and suicidality on CSA.

PMID- 17522002
TI  - Community notification: perceptions of its effectiveness in preventing child
      sexual abuse.
AB  - Megan's law, a law designed to protect children from sexual abuse, enables law
      enforcement to notify communities when convicted sex offenders reside in their
      neighborhoods. Although there is vast support for the law, little is known about
      the perceived efficacy of the law. Community members', law enforcement
      officials', and law students' attitudes toward community notification and other
      child abuse prevention measures were investigated. The groups significantly
      differed in support of Megan's Law and surrounding issues, such as whether all
      criminals should be subject to community notification. Also, perceptions of the
      efficacy and the degree to which offenders' rights are violated differed
      according to whether community notification tactics were typical or extreme.

PMID- 17522003
TI  - Treatment provider awareness of the possible impact of the internet on the
      treatment of sex offenders: an alert to a problem.
AB  - This study evaluated treatment providers' perceptions of the impact of the
      Internet on the treatment of sex offenders. This study surveyed all of the
      agencies in South Carolina that provide treatment services for sex offenders.
      Analysis indicated that (a) most treatment providers were unaware of the
      potential negative impact of the Internet on their treatment efforts with
      clients, (b) most treatment providers had no policy restricting their clients'
      Internet use, (c) the overwhelming majority of treatment providers felt that they
      were poorly equipped to deal with this issue, and (d) almost all of the treatment
      providers felt that probation and parole would be of little assistance in helping
      them monitor their clients' use of the Internet. Implications of the findings for
      improving treatment services for sex offenders were explored and discussed.

PMID- 17522004
TI  - Assessment of the integration of AAMC Medical Informatics Objectives into the
      medical school curriculum.
AB  - The School of Medicine at the Medical College of Virginia Campus of Virginia
      Commonwealth University examined the 2005/2006 medical school curriculum to
      ensure that students were prepared to meet the informatics objectives put forward
      by the AAMC Medical School Objectives Project published in 1998. The AAMC Medical
      Informatics Objectives Survey, issued in 2005, led the VCU School of Medicine to
      investigate the points of integration between informatics objectives and course
      syllabi for the first three years of the medical school curriculum. This analysis
      raised awareness of the informatics objectives with SOM faculty and staff and
      showed that more than 74% of the informatics objectives have been integrated into
      the curriculum.

PMID- 17522005
TI  - ICONic training: use of a course management system to provide continual reference
      student education.
AB  - In an effort to provide continuing education to the students working at the
      Hardin Library reference desk, staff members have created an online training
      course using the University of Iowa's course management system called ICON(Iowa
      Courses Online). The course has four main components-a content page, an article
      discussion forum, quizzes, and a challenging questions module. ICON has quickly
      become an essential training resource and has also provided an electronic
      professional community for students who primarily work in isolation.
      Additionally, the experience with the software has positioned the library to
      provide training support for the health campus and to take advantage of new
      technology based collaborations.

PMID- 17522006
TI  - Use of laptop computers in an academic medical library.
AB  - Who borrows laptop computers in an academic health sciences library? Why do they
      choose to check out laptops? In a survey, laptop computer users responded that
      the laptops were used most frequently to do class-related work. Laptops were most
      often checked out because they could be taken to a quiet area of the library or
      to where the user had more room to work. The majority of such borrowers were
      satisfied or very satisfied with the laptops and the service from the library.
      The majority of those completing the survey were medical school students and
      graduate students. The circulation of laptop computers at this academic health
      sciences library is a very successful and popular program.

PMID- 17522007
TI  - Approaching usability: a study of an academic health sciences library web site.
AB  - A usability study was conducted at a medium-sized academic health sciences
      library with the goal of providing data to inform the future redesign of the
      library's Web page. A two-stage approach was used: (1) A preliminary survey
      designed to identify common tasks and issues on which to focus, and (2) usability
      testing. Responses to the survey indicated general satisfaction with the site and
      suggested areas for testing. Usability testing participants were asked to perform
      scripted tasks. The results indicate that users do have considerable difficulty
      navigating the site and recommendations are presented. This method of testing is
      recommended for health sciences libraries.

PMID- 17522008
TI  - REHABDATA: a disability and rehabilitation information resource.
AB  - The National Rehabilitation Information Center's REHABDATA database contains
      about 69,000 abstracts on information contained in published books, reports, and
      articles, as well as audiovisual materials. All information contained relates to
      the topic of disability and rehabilitation research. This column will provide
      background information on the REHABDATA file and include some basic search hints
      and features.

PMID- 17522009
TI  - Controversial issues: euthanasia - a guide to resources.
AB  - The purpose of this resource guide is to provide health sciences, medical, and
      large libraries a description of the content and features of the most popular Web
      sites on euthanasia. The redundancy in results of searches of the term
      "euthanasia" in multiple search engines indicates the high likelihood that
      information seekers will be directed to one or more of these sites. The eight
      most frequently retrieved sites are discussed here with attention paid to
      position (i.e., pro- or anti-euthanasia), authority, degree and quality of
      linkage, and uniqueness of information provided. These descriptions should help
      librarians direct their users to appropriate sources of information about
      euthanasia on the Web.

PMID- 17522010
TI  - Creating the first MedlinePlus "Go Local" service: lessons and recommendations
      from the evaluation of NC Health Info.
AB  - NC Health Info is an online collection of North Carolina based health services
      Web sites that seamlessly links local health resources to topical health
      information on MedlinePlus, the National Library of Medicine's consumer health
      information Web site. NC Health Info was the first project to connect local
      resources with MedlinePlus in the "Go Local" initiative. As such, NC Health Info
      serves as a model for other states to follow in connecting their own local
      information with Medline- Plus. This paper describes the processes used and
      lessons learned during a year-long evaluation of NC Health Info. Evaluation
      results may be of interest and applicable to any existing or planned "Go Local"
      project.

PMID- 17522011
TI  - The Bioinformatics Program at Washington University's Bernard Becker Medical
      Library: making it happen.
AB  - The need for a Bioinformatics Program became apparent after repeated requests
      from researchers for bioinformatics resources and the University's announcement
      of BioMed 21, a 300 million dollars biomedical science initiative to bring "new
      knowledge of the human genetic blueprint to the patient's bedside and change how
      illnesses are understood, diagnosed, and successfully treated." A Bioinformatics
      Specialist with a strong background in the fields of Molecular Biology and
      Biostatistics was hired. Program development started in 2003. Initially, three
      core courses were developed: Sequence Similarity Search, Genetic Variation, and
      Human Genome Resources. Each of these courses was offered twice per semester.
      Additionally, partnerships were established within the University Medical School
      Community (e.g., the Genome Sequencing Center) to license and teach Spotfire's
      DecisionSite for Functional Genomics, a software package used to analyze
      microarray data. From March to May 2005, seven Spotfire classes were taught. Each
      Spotfire class consisted of seven hours of classroom work. Also, in-depth
      consultations were scheduled with faculty and researchers to address their
      specific needs. These consultations led to requests for other software packages
      to purchase and manage, including Lasergene and CSD (Cambridge Crystal Structure
      Database). Efforts to reach outside of the University Community were made through
      the development of a Bioinformatics Web site.

PMID- 17522014
TI  - Improving surveillance for antimalarial drug resistance.

PMID- 17522015
TI  - Histone modifications around individual BDNF gene promoters in prefrontal cortex
      are associated with extinction of conditioned fear.
AB  - Extinction of conditioned fear is an important model both of inhibitory learning
      and of behavior therapy for human anxiety disorders. Like other forms of
      learning, extinction learning is long-lasting and depends on regulated gene
      expression. Epigenetic mechanisms make an important contribution to persistent
      changes in gene expression; therefore, in these studies, we have investigated
      whether epigenetic regulation of gene expression contributes to fear extinction.
      Since brain-derived neurotrophic factor (BDNF) is crucial for synaptic plasticity
      and for the maintenance of long-term memory, we examined histone modifications
      around two BDNF gene promoters after extinction of cued fear, as potential
      targets of learning-induced epigenetic regulation of gene expression. Valproic
      acid (VPA), used for some time as an anticonvulsant and a mood stabilizer,
      modulates the expression of BDNF, and is a histone deacetylase (HDAC) inhibitor.
      Here, we report that extinction of conditioned fear is accompanied by a
      significant increase in histone H4 acetylation around the BDNF P4 gene promoter
      and increases in BDNF exon I and IV mRNA expression in prefrontal cortex, that
      VPA enhances long-term memory for extinction because of its HDAC inhibitor
      effects, and that VPA potentiates the effect of weak extinction training on
      histone H4 acetylation around both the BDNF P1 and P4 gene promoters and on BDNF
      exon IV mRNA expression. These results suggest a relationship between histone H4
      modification, epigenetic regulation of BDNF gene expression, and long-term memory
      for extinction of conditioned fear. In addition, they suggest that HDAC
      inhibitors may become a useful pharmacological adjunct to psychotherapy for human
      anxiety disorders.

PMID- 17522016
TI  - Monocular deprivation in adult mice alters visual acuity and single-unit
      activity.
AB  - It has been discovered recently that monocular deprivation in young adult mice
      induces ocular dominance plasticity (ODP). This contradicts the traditional
      belief that ODP is restricted to a juvenile critical period. However, questions
      remain. ODP of young adults has been observed only using methods that are
      indirectly related to vision, and the plasticity of young adults appears
      diminished in comparison with juveniles. Therefore, we asked whether the newly
      discovered adult ODP broadly reflects plasticity of visual cortical function and
      whether it persists into full maturity. Single-unit activity is the standard
      physiological marker of visual cortical function. Using a more optimized protocol
      for recording single-units, we find evidence of adult ODP of single-units and
      show that it is most pronounced in deep cortical layers. Furthermore, using
      visual evoked potentials (VEP), we find that ODP is equally robust in young
      adults and mature adults and is observable after just one day of monocular
      deprivation. Finally, we find that monocular deprivation in adults changes
      spatial frequency thresholds of the VEP, decreasing the acuity of the deprived
      pathway and improving the acuity of the non-deprived pathway. Thus, in mice, the
      primary visual cortex is capable of remarkable adaptation throughout life.

PMID- 17522017
TI  - Effects of paradigm and inter-stimulus interval on age differences in eyeblink
      classical conditioning in rabbits.
AB  - The aim of this study was to examine parameters affecting age differences in
      eyeblink classical conditioning in a large sample of young and middle-aged
      rabbits. A total of 122 rabbits of mean ages of 4 or 26 mo were tested at inter
      stimulus intervals (ISIs) of 600 or 750 msec in the delay or trace paradigms.
      Paradigm affected both age groups dramatically, with superior performance in the
      delay paradigm. ISI was salient as middle-aged rabbits were significantly
      impaired in 750-msec compared with 600-msec delays, and young rabbits were
      significantly less impaired in 600-msec than in 750-msec trace. Young rabbits
      performed equally well at both delay ISIs, and consequently, there were
      significant age differences in 750-msec but not in 600-msec delays. Middle-aged
      rabbits performed poorly at both 600- and 750-msec trace, resulting in
      significant age differences in 600-msec but not in 750-msec trace. Timing of the
      conditioned response has been associated with cerebellar cortical function.
      Normal aging of the cerebellar cortex likely contributed to the magnitude of the
      effect of ISI in delay conditioning in middle-aged rabbits. Results demonstrate
      that the magnitude of age differences in eyeblink conditioning can be enlarged or
      eliminated by ISI and paradigm.

PMID- 17522018
TI  - Reconsolidation of declarative memory in humans.
AB  - The reconsolidation hypothesis states that a consolidated memory could again
      become unstable and susceptible to facilitation or impairment for a discrete
      period of time after a reminder presentation. The phenomenon has been
      demonstrated in very diverse species and types of memory, including the human
      procedural memory of a motor skill task but not the human declarative one. Here
      we provide evidence for both consolidation and reconsolidation in a paired
      associate learning (i.e., learning an association between a cue syllable and the
      respective response syllable). Subjects were given two training sessions with a
      24-h interval on distinct verbal material, and afterward, they received at
      testing two successive retrievals corresponding to the first and second learning,
      respectively. Two main results are noted. First, the first acquired memory was
      impaired when a reminder was presented 5 min before the second training
      (reconsolidation), and also when the second training was given 5 min instead of
      24 h after the first one (consolidation). Second, the first retrieval proved to
      influence negatively on the later one (the retrieval-induced forgetting [RIF]
      effect), and we used the absence of this RIF effect as a very indicator of the
      target memory impairment. We consider the demonstration of reconsolidation in
      human declarative memory as backing the universality of this phenomenon and
      having potential clinical relevance. On the other hand, we discuss the
      possibility of using the human declarative memory as a model to address several
      key topics of the reconsolidation hypothesis.

PMID- 17522020
TI  - Memory for context becomes less specific with time.
AB  - Context memories initially require the hippocampus, but over time become
      independent of this structure. This shift reflects a consolidation process
      whereby memories are gradually stored in distributed regions of the cortex. The
      function of this process is thought to be the extraction of statistical
      regularities and general knowledge from specific experiences. The current study
      examined this idea in mice by measuring the specificity of context memories
      during consolidation. In the first experiment, separate groups of animals were
      trained with a single shock and tested in the training context or a novel
      environment 1, 14, 28, or 36 d later. We found a systematic increase in
      generalization over this period. Initially, mice froze more in the training
      context, but fear of the novel environment grew over time until animals
      eventually froze an equivalent amount in both contexts. The second experiment
      demonstrated that the increase in generalization was due to a loss of detailed
      information about the context and not fear incubation. In this experiment, mice
      were exposed to the context and then trained with an immediate shock 1 or 36 d
      later. Animals trained 1 d after exposure acquired robust context fear that did
      not generalize across environments. In contrast, mice trained 36 d after exposure
      froze an equivalent amount in the training context and the novel environment. The
      same profile was observed in H-ras mutants that exhibit enhanced hippocampal
      plasticity and learning. These results suggest that context memories are specific
      early after training when they require the hippocampus, and become more general
      as they are permanently stored in the cortex.

PMID- 17522019
TI  - Alteration of cingulate long-term plasticity and behavioral sensitization to
      inflammation by environmental enrichment.
AB  - Exposure to an enriched environment (EE) has been shown to induce cortical
      plasticity. Considerable amount of research is focused on the effects of EE in
      the hippocampus; however, effects of EE on other brain regions and the mechanisms
      involved are not well known. To investigate this, we induced cortical plasticity
      by placing mice in an EE for one month and measured the effects of EE in the
      anterior cingulate cortex (ACC). Here, we show that EE enhanced the expression of
      the plasticity gene, egr-1, in the ACC of EE animals accompanied by enhanced
      cingulate long-term potentiation (LTP) and decreased cingulate long-term
      depression (LTD). The increased NMDA receptor NR2B/NR2A subunits current ratio is
      associated with the plasticity seen in the ACC while total protein levels remain
      unchanged. Furthermore, behavioral experiments show that these mice exposed to EE
      demonstrate enhanced responses to acute and long-term inflammation. Our findings
      suggest that exposure to EE alters physiological properties within the ACC which
      results in enhanced responses to inflammation.

PMID- 17522021
TI  - Hippocampal regulation of context-dependent neuronal activity in the lateral
      amygdala.
AB  - Pavlovian fear conditioning is a robust and enduring form of emotional learning
      that provides an ideal model system for studying contextual regulation of memory
      retrieval. After extinction the expression of fear conditional responses (CRs) is
      context-specific: A conditional stimulus (CS) elicits greater conditional
      responding outside compared with inside the extinction context. Dorsal
      hippocampal inactivation with muscimol attenuates context-specific CR expression.
      We have previously shown that CS-elicited spike firing in the lateral nucleus of
      the amygdala is context-specific after extinction. The present study examines
      whether dorsal hippocampal inactivation with muscimol disrupts context-specific
      firing in the lateral amygdala. We conditioned rats to two separate auditory CSs
      and then extinguished each CS in separate and distinct contexts. Thereafter,
      single-unit activity and conditional freezing were tested to one CS in both
      extinction contexts after saline or muscimol infusion into the dorsal
      hippocampus. After saline infusion, rats froze more to the CS when it was
      presented outside of its extinction context, but froze equally in both contexts
      after muscimol infusion. In parallel with the behavior, lateral nucleus neurons
      exhibited context-dependent firing to extinguished CSs, and hippocampal
      inactivation disrupted this activity pattern. These data reveal a novel role for
      the hippocampus in regulating the context-specific firing of lateral amygdala
      neurons after fear memory extinction.

PMID- 17522022
TI  - Withdrawal from cocaine self-administration produces long-lasting deficits in
      orbitofrontal-dependent reversal learning in rats.
AB  - Drug addicts make poor decisions. These decision-making deficits have been
      modeled in addicts and laboratory animals using reversal-learning tasks. However,
      persistent reversal-learning impairments have been shown in rats and monkeys only
      after noncontingent cocaine injections. Current thinking holds that to represent
      the human condition effectively, animal models of addiction must utilize self
      administration procedures in which drug is earned contingently; thus, it remains
      unclear whether reversal-learning deficits caused by noncontingent cocaine
      exposure are relevant to addiction. To test whether reversal learning deficits
      are caused by contingent cocaine exposure, we trained rats to self-administer
      cocaine, assessed cue-induced cocaine seeking in extinction tests after 1 and 30
      d of withdrawal, and then tested for reversal learning more than a month later.
      We found robust time-dependent increases in cue-induced cocaine seeking in the
      two extinction tests (incubation of craving) and severe reversal-learning
      impairments.

PMID- 17522023
TI  - Acute exposure to stress improves performance in trace eyeblink conditioning and
      spatial learning tasks in healthy men.
AB  - The present study investigated the effects of acute stress exposure on learning
      performance in humans using analogs of two paradigms frequently used in animals.
      Healthy male participants were exposed to the cold pressor test (CPT) procedure,
      i.e., insertion of the dominant hand into ice water for 60 sec. Following the CPT
      or the control procedure, participants completed a trace eyeblink conditioning
      task followed by a virtual navigation Morris water task (VNMWT). Hypothalamic
      pituitary-adrenocortical (HPA) axis and sympathetic autonomic system (SAS)
      activity were assessed by measuring salivary cortisol, heart rate, and skin
      conductance at selected timepoints. Results revealed positive effects of stress
      on performance in both tasks. The stress group showed significantly more
      conditioned blinks than the control group during acquisition of trace eyeblink
      conditioning. The stress group also performed significantly better in the VNMWT
      than the control group, with the former showing significantly fewer failures to
      locate the hidden platform in the allotted time and smaller heading errors than
      the latter. Regression analyses revealed positive relationships between HPA axis
      and SAS activity during stress and eyeblink conditioning performance. Our results
      directly extend findings from animal studies and suggest potential physiological
      mechanisms underlying stress and learning.

PMID- 17522024
TI  - Midlife decline in declarative memory consolidation is correlated with a decline
      in slow wave sleep.
AB  - Sleep architecture as well as memory function are strongly age dependent. Slow
      wave sleep (SWS), in particular, decreases dramatically with increasing age,
      starting already beyond the age of 30. SWS normally predominates during early
      nocturnal sleep and is implicated in declarative memory consolidation. However,
      the consequences of changes in sleep across the life span for sleep-associated
      memory consolidation have not been evaluated so far. Here, we compared
      declarative memory consolidation (for word-pair associates) during sleep in young
      and middle-aged healthy humans. The age groups (18-25 vs. 48-55 yr) did not
      differ with regard to learning performance before retention periods that covered,
      respectively, the first and second half of nocturnal sleep. However, after early
      retention sleep, where the younger subjects showed distinctly more SWS than the
      middle-aged (62.3 +/- 3.7 min vs. 18.4 +/- 7.2 min, P < 0.001), retrieval of the
      word pairs in the middle-aged was clearly worse than in the young (P < 0.001). In
      contrast, declarative memory retention did not differ between groups after late
      sleep, where retention was generally worse than after early sleep (P = 0.005).
      Retention of declarative memories was the same in both age groups when sleep
      periods containing equal amounts of SWS were compared, i.e., across late sleep in
      the young and across early sleep in the middle-aged. Our results indicate a
      decline in sleep-associated declarative memory consolidation that develops
      already during midlife and is associated with a decrease in early nocturnal SWS.

PMID- 17522025
TI  - Natural variation in Drosophila larval reward learning and memory due to a cGMP
      dependent protein kinase.
AB  - Animals must be able to find and evaluate food to ensure survival. The ability to
      associate a cue with the presence of food is advantageous because it allows an
      animal to quickly identify a situation associated with a good, bad, or even
      harmful food. Identifying genes underlying these natural learned responses is
      essential to understanding this ability. Here, we investigate whether natural
      variation in the foraging (for) gene in Drosophila melanogaster larvae is
      important in mediating associations between either an odor or a light stimulus
      and food reward. We found that for influences olfactory conditioning and that the
      mushroom bodies play a role in this for-mediated olfactory learning. Genotypes
      associated with high activity of the product of for, cGMP-dependent protein
      kinase (PKG), showed greater memory acquisition and retention compared with
      genotypes associated with low activity of PKG when trained with three
      conditioning trials. Interestingly, increasing the number of training trials
      resulted in decreased memory retention only in genotypes associated with high PKG
      activity. The difference in the dynamics of memory acquisition and retention
      between variants of for suggests that the ability to learn and retain an
      association may be linked to the foraging strategies of the two variants.

PMID- 17522026
TI  - Rapid forgetting of social transmission of food preferences in aged rats:
      relationship to hippocampal CREB activation.
AB  - A major characteristic of age-related changes in memory in rodents is an increase
      in the rate of forgetting of new information, even when tests given soon after
      training reveal intact memory. Interference with CREB functions similarly results
      in rapid decay of memory. Using quantitative immunocytochemistry, the present
      experiment examined the number of CREB- and pCREB-immunoreactive neurons in three
      regions of the dorsal and ventral hippocampus (dentate gyrus, CA3, and CA1) as a
      function of age and training. Rats were trained in a social transmission of food
      preference task. Using different food pairings, memory was tested in each rat
      immediately and 1, 2, 3, and 7 d later. Both young and old rats had intact and
      comparable memory scores at the immediate and 24-h tests, but old rats exhibited
      more rapid forgetting thereafter relative to that of young rats. The main
      findings were that training resulted in large increases in the number of pCREB
      immunoreactive cells throughout the hippocampus in both young and aged rats.
      However, particularly in the ventral hippocampus, the training-elicited increase
      in pCREB-positive neurons was significantly lower in old than in young rats.
      Based on Western blot analyses in a separate set of rats, CREB levels were not
      responsive to training but were lower in the ventral hippocampus of old rats than
      of young rats. The present findings suggest that lower activation of CREB after
      training may contribute to the rapid forgetting seen in aged rats.

PMID- 17522028
TI  - Neurogenesis and the spacing effect: learning over time enhances memory and the
      survival of new neurons.
AB  - Information that is spaced over time is better remembered than the same amount of
      information massed together. This phenomenon, known as the spacing effect, was
      explored with respect to its effect on learning and neurogenesis in the adult
      dentate gyrus of the hippocampal formation. Because the cells are generated over
      time and because learning enhances their survival, we hypothesized that training
      with spaced trials would rescue more new neurons from death than the same number
      of massed trials. In the first experiment, animals trained with spaced trials in
      the Morris water maze outperformed animals trained with massed trials, but there
      was not a direct effect of trial spacing on cell survival. Rather, animals that
      learned well retained more cells than animals that did not learn or learned
      poorly. Moreover, performance during acquisition correlated with the number of
      cells remaining in the dentate gyrus after training. In the second experiment,
      the time between blocks of trials was increased. Consequently, animals trained
      with spaced trials performed as well as those trained with massed, but remembered
      the location better two weeks later. The strength of that memory correlated with
      the number of new cells remaining in the hippocampus. Together, these data
      indicate that learning, and not mere exposure to training, enhances the survival
      of cells that are generated 1 wk before training. They also indicate that
      learning over an extended period of time induces a more persistent memory, which
      then relates to the number of cells that reside in the hippocampus.

PMID- 17522027
TI  - Corticosterone time-dependently modulates beta-adrenergic effects on long-term
      potentiation in the hippocampal dentate gyrus.
AB  - Previous experiments in the hippocampal CA1 area have shown that corticosterone
      can facilitate long-term potentiation (LTP) in a rapid non-genomic fashion, while
      the same hormone suppresses LTP that is induced several hours after hormone
      application. Here, we elaborated on this finding by examining whether
      corticosterone exerts opposite effects on LTP depending on the timing of hormone
      application in the dentate gyrus as well. Moreover, we tested rapid and delayed
      actions by corticosterone on beta-adrenergic-dependent changes in LTP. Unlike the
      CA1 region, our in vitro field potential recordings show that rapid effects of
      corticosterone do not influence LTP induced by mild tetanization in the
      hippocampal dentate gyrus, unless GABA(A) receptors are blocked. In contrast, the
      beta-adrenergic agonist isoproterenol does initiate a slow-onset, limited amount
      of potentiation. When corticosterone was applied concurrently with isoproterenol,
      a further enhancement of synaptic strength was identified, especially during the
      early stage of potentiation. Yet, treatment with corticosterone several hours in
      advance of isoproterenol fully prevented any effect of isoproterenol on LTP. This
      emphasizes that corticosterone can regulate beta-adrenergic modulation of
      synaptic plasticity in opposite directions, depending on the timing of hormone
      application.

PMID- 17522029
TI  - Protection from premature habituation requires functional mushroom bodies in
      Drosophila.
AB  - Diminished responses to stimuli defined as habituation can serve as a gating
      mechanism for repetitive environmental cues with little predictive value and
      importance. We demonstrate that wild-type animals diminish their responses to
      electric shock stimuli with properties characteristic of short- and long-term
      habituation. We used spatially restricted abrogation of neurotransmission to
      identify brain areas involved in this behavioral response. We find that the
      mushroom bodies and, in particular, the alpha/beta lobes appear to guard against
      habituating prematurely to repetitive electric shock stimuli. In addition to
      protection from premature habituation, the mushroom bodies are essential for
      spontaneous recovery and dishabituation. These results reveal a novel modulatory
      role of the mushroom bodies on responses to repetitive stimuli in agreement with
      and complementary to their established roles in olfactory learning and memory.

PMID- 17522030
TI  - Novel Al2O3:C,Mg fluorescent nuclear track detectors for passive neutron
      dosimetry.
AB  - The latest advances in the development of a fluorescent nuclear track detector
      (FNTD) for neutron and heavy charged particle dosimetry are described and
      compared with CR-39 plastic nuclear etched track detectors (PNTDs). The technique
      combines a new luminescent aluminium oxide single crystal detector
      (Al(2)O(3):C,Mg) with an imaging technique based on laser scanning and confocal
      fluorescence detection. Detection efficiency was obtained after irradiations with
      monoenergetic neutron and proton beams. Dose dependences were measured for
      different configurations of the detectors exposed in fast- and thermal-neutron
      fields. A specially developed image processing technique allows for fast
      fluorescent track identification and counting. The readout method is non
      destructive, and detectors can be reused after thermal annealing.

PMID- 17522031
TI  - Modification of ROSPEC to cover neutrons from thermal to 18 MeV.
AB  - Rotating Spectrometer (ROSPEC) is a neutron spectrometer designed to measure
      neutron energy distributions, and provide accurate neutron dosimetry. It is a
      completely self-contained unit and measures neutron energy via recoiling protons
      in gas proportional counters. Each of the four original gas counters is dedicated
      to a particular neutron energy range dictated by sensitivity to gamma rays at the
      low energy end of the spectrum and by proton collisions with the counter walls at
      the high energy end. Introduced originally in 1992, ROSPEC has a proven
      operational record with a program of continued upgrades. The operating range of
      the original ROSPEC spans 50 keV-4.5 MeV. The range of the ROSPEC has now been
      extended down to include epithermal and thermal neutrons by adding two 2 in.
      (3)He counters. Also, an optional simple scintillation spectrometer was designed
      to extend the upper limit of ROSPEC up to 18 MeV.

PMID- 17522032
TI  - Experimental and theoretical study of the neutron dose produced by carbon ion
      therapy beams.
AB  - High-energy (12)C ions offer favourable conditions for the treatment of deep
      seated local tumours. Several facilities for the heavy ion therapy are planned or
      under construction, for example the new clinical ion-therapy unit HIT at the
      Radiological University Clinics in Heidelberg. In order to improve existing
      treatment planning models, it is essential to evaluate the secondary fragment
      production and to include these contributions to the therapy dose with higher
      accuracy. Secondary neutrons are most abundantly produced in the reactions
      between (12)C beams and tissues. The dose contribution to tissues by a neutron is
      fairly small compared with the projectile and the other charged fragments due to
      no ionisation and the small reaction cross-sections; however, it distributes in a
      considerably wider region beyond the bragg-peak because of the strong
      penetrability. Systematic data on energy spectra and doses of secondary neutrons
      produced by (12)C beams using water targets of different thicknesses for various
      detection angles have therefore been measured in this study at GSI Darmstadt.

PMID- 17522033
TI  - Normalisation of prescribed dose in BNCT.
AB  - Normalisation of prescribed dose in boron neutron capture therapy (BNCT) is
      needed to facilitate combining clinical data from different centres in the world
      to help expedite development of the modality. The approach being pursued within
      the BNCT community is based upon improving precision in the measurement and
      specification of absorbed dose. Beam characterisations using a common method are
      complete as are comparative dosimetry measurements between clinical centres in
      Europe and the USA. Results from treatment planning systems at these centres have
      been compared with measurements performed by MIT, and the scale factors
      determined are being confirmed with independent tests using measurements in an
      ellipsoidal water phantom. Dose normalisations have successfully been completed
      and applied to retrospectively analyse treatment plans from Brookhaven National
      Laboratory (1994-99) so that reported doses are consistently expressed with the
      trials performed during 1994-2003 at Harvard-MIT. Dose response relationships for
      adverse events and other endpoints can now be more accurately established.

PMID- 17522034
TI  - Artificial neural networks technology for neutron spectrometry and dosimetry.
AB  - Artificial Neural Network Technology has been applied to unfold neutron spectra
      and to calculate 13 dosimetric quantities using seven count rates from a Bonner
      Sphere Spectrometer with a (6)LiI(Eu). Two different networks, one for
      spectrometry and another for dosimetry, were designed. To train and test both
      networks, 177 neutron spectra from the IAEA compilation were utilised. Spectra
      were re-binned into 31 energy groups, and the dosimetric quantities were
      calculated using the MCNP code and the fluence-to-dose conversion coefficients
      from ICRP 74. Neutron spectra and UTA4 response matrix were used to calculate the
      expected count rates in the Bonner spectrometer. Spectra and H(10) of (239)PuBe
      and (241)AmBe were experimentally obtained and compared with those determined
      with the artificial neural networks.

PMID- 17522035
TI  - Meeting new challenges in radon measurements service with solid state alpha track
      analysis.
AB  - The national and international radioprotection legislation now covers exposures
      to the naturally occurring radioactive materials (NORM) with particular emphasis
      on radon in workplaces. Consequently, a number of working environments have now
      been brought into the realm of radiation protection monitoring with a
      corresponding increase in the demand for radon monitoring services. The new
      challenges occasioned by the increase in demands are illustrated in this paper
      together with the radon measurement system developed at the ENEA IRP radon
      Service. In particular, this paper emphasises how to control using hardware and
      software analysis, the distributions (diameters and areas) of the track shape,
      which directly affect the quality of the radon service.

PMID- 17522036
TI  - High-energy response of passive dosemeters in use at LANL.
AB  - The high-energy neutron response of three passive dosemeters in use at the Los
      Alamos National Laboratory (LANL) has been investigated using metrology-grade
      fields. The dosemeters include the LANL Model 8823 TLD badge and the LANL PN3
      track etch device. Both are dosemeters of record at LANL. The third device was
      the Personal Neutron Dosemeter (PND), a superheated emulsion device, manufactured
      by Bubble Technology Industries, Inc. (BTI). The response of the three dosemeters
      at neutron energies exceeding 10 MeV was assessed with monoenergetic neutrons at
      the Physikalisch-Technische Bundesanstalt facility (14.8 and 19 MeV). For the
      sake of completeness, data collected at lower energies are also included in this
      study. High-energy quasi-monoenergetic beams produced by the cyclotron facilities
      at the Universite Catholique de Louvain (UCL) and the The Svedberg Laboratory
      (TSL) were also utilised as part of this study. These measurements were made to
      better understand and help interpret dosemeter readings obtained by workers at
      high-energy accelerators, such as the 800 MeV spallation neutron source facility
      located at the Los Alamos Neutron Science Center (LANSCE).

PMID- 17522037
TI  - Neutron spectrometry with a monolithic silicon telescope.
AB  - A neutron spectrometer was set-up by coupling a polyethylene converter with a
      monolithic silicon telescope, consisting of a DeltaE and an E stage-detector
      (about 2 and 500 microm thick, respectively). The detection system was irradiated
      with monoenergetic neutrons at INFN-Laboratori Nazionali di Legnaro (Legnaro,
      Italy). The maximum detectable energy, imposed by the thickness of the E stage,
      is about 8 MeV for the present detector. The scatter plots of the energy
      deposited in the two stages were acquired using two independent electronic
      chains. The distributions of the recoil-protons are well-discriminated from those
      due to secondary electrons for energies above 0.350 MeV. The experimental spectra
      of the recoil-protons were compared with the results of Monte Carlo simulations
      using the FLUKA code. An analytical model that takes into account the geometrical
      structure of the silicon telescope was developed, validated and implemented in an
      unfolding code. The capability of reproducing continuous neutron spectra was
      investigated by irradiating the detector with neutrons from a thick beryllium
      target bombarded with protons. The measured spectra were compared with data taken
      from the literature. Satisfactory agreement was found.

PMID- 17522038
TI  - Field calibration studies for ionisation chambers in mixed high-energy radiation
      fields.
AB  - The monitoring of ambient doses at work places around high-energy accelerators is
      a challenging task due the complexity of the mixed stray radiation fields
      encountered. At CERN, mainly Centronics IG5 high-pressure ionisation chambers are
      used to monitor radiation exposure in mixed fields. The monitors are calibrated
      in the operational quantity ambient dose equivalent H*(10) using standard, source
      generated photon- and neutron fields. However, the relationship between
      ionisation chamber reading and ambient dose equivalent in a mixed high-energy
      radiation field can only be assessed if the spectral response to every component
      and the field composition is known. Therefore, comprehensive studies were
      performed at the CERN-EU high-energy reference field facility where the spectral
      fluence for each particle type has been assessed with Monte Carlo simulations.
      Moreover, studies have been performed in an accessible controlled radiation area
      in the vicinity of a beam loss point of CERN's proton synchrotron. The comparison
      of measurements and calculations has shown reasonable agreement for most exposure
      conditions. The results indicate that conventionally calibrated ionisation
      chambers can give satisfactory response in terms of ambient dose equivalent in
      stray radiation fields at high-energy accelerators in many cases. These studies
      are one step towards establishing a method of 'field calibration' of radiation
      protection instruments in which Monte Carlo simulations will be used to establish
      a correct correlation between the response of specific detectors to a given high
      energy radiation field.

PMID- 17522039
TI  - CHELSI: a portable neutron spectrometer for the 20-800 MeV region.
AB  - CHELSI is a CsI-based portable spectrometer being developed at Los Alamos
      National Laboratory for use in high-energy neutron fields. Based on the inherent
      pulse shape discrimination properties of CsI(Tl), the instrument flags charged
      particle events produced via neutron-induced spallation events. Scintillation
      events are processed in real time using digital signal processing and a
      conservative estimate of neutron dose rate is made based on the charged particle
      energy distribution. A more accurate dose estimate can be made by unfolding the
      2D charged particle versus pulse height distribution to reveal the incident
      neutron spectrum from which dose is readily obtained. A prototype probe has been
      assembled and data collected in quasi-monoenergetic fields at The Svedberg
      Laboratory (TSL) in Uppsala as well as at the Los Alamos Neutron Science Center
      (LANSCE). Preliminary efforts at deconvoluting the shape/energy data using
      empirical response functions derived from time-of-flight measurements are
      described.

PMID- 17522040
TI  - Neutron response of the chlorobenzene-ethanol-trimethylpentane dosimetry system.
AB  - The dosimetric use of the chemical solution chlorobenzene-ethanol
      trimethylpentane (CET) is based on the radiolytic formation of hydrochloric acid,
      which protonates a pH indicator thymolsulphonphthalein. On the basis of the CET
      solution, an accident and emergency personal dosemeter was designed allowing
      doses in the range 0.2-15 Gy can be measured. Radiation-chemical yields, G(HCl),
      for the CET system, and the responses of dosemeters in different neutron fields,
      ranging from 0.35 to 19.3 MeV mean energy neutrons, are summarised. The relation
      of G(HCl) to linear energy transfer (LET) of incident heavy charged particles is
      also evaluated on the basis of the previously published data. The response of the
      CET system to monoenergetic neutrons was calculated from the measured dependence
      of the G value upon LET of heavy charged particles and data about the LET
      distribution for monoenergetic neutrons. A very good agreement between this
      calculation and the experimental results was obtained. These results enable
      predictions of the response to be made in radiation fields with the known LET
      distributions.

PMID- 17522041
TI  - Quantum molecular dynamics calculation of light-ion production in neutron-induced
      reactions at intermediate energies.
AB  - A quantum molecular dynamics (QMD) simulation is applied to light-ion production
      in neutron-induced reactions on O, Si and Fe at E(n) = 96 MeV. The generalized
      evaporation model (GEM) is used to account for statistical decay processes after
      the QMD stage. Good agreement with the experimental energy spectra is obtained
      for proton emission, but the calculation exhibits remarkable underestimation for
      pre-equilibrium emission of light clusters, i.e. d, t, (3)He and (4)He. It is
      found that the underestimation is improved except in the region around the high
      energy end of the emission spectra by implementation of a phenomenological
      coalescence model into the QMD under the assumption that these light clusters are
      formed in the nuclear surface region by a leading nucleon that is ready to leave
      the nucleus.

PMID- 17522042
TI  - Application of voxel phantoms and Monte Carlo method to whole-body counter
      calibration.
AB  - Voxel phantoms and Monte Carlo methods are of considerable interest in
      calibrating in vivo counting applications for radioactive body burden such as
      whole-body counters. At the Japan Atomic Energy Research Institute (JAERI), a
      calculation code--UCWBC code--for whole-body counter calibrations using voxel
      phantoms has been developed as an EGS4 Monte Carlo user code. To validate the
      UCWBC code for calibrating whole-body counters at JAERI, response functions and
      counting efficiencies of a p-type high-purity Ge (HPGe) semiconductor detector
      used for the whole-body counter were evaluated for a water-filled block-shape
      phantom by use of UCWBC code and were measured by experiments. The voxel version
      of the water-filled block-shape phantom based on an actual phantom was used for
      the calculations. Furthermore, counting efficiencies of the Ge semiconductor
      detector for the male and female voxel phantoms developed at JAERI were evaluated
      in the photon energy range from 60 to 1836 keV by the UCWBC code in order to
      examine the differences between the counting efficiencies for voxel phantoms. In
      conclusion, it was found that the response functions and counting efficiencies of
      the Ge semiconductor detector found by the UCWBC code for the water-filled block
      shape phantom are in good agreement with measured data. The UCWBC code was
      validated by those comparisons. It was also found that the counting efficiencies
      of the Ge semiconductor detector depend on the size of the phantoms and the
      effective distance between phantom and detector. The calibration of whole-body
      counters using voxel phantoms and Monte Carlo methods would be quite useful for
      the improvement in the accuracy of measurement results.

PMID- 17522043
TI  - Evaluation of individual dosimetry in mixed neutron and photon radiation fields
      (EVIDOS). Part I: Scope and methods of the project.
AB  - Supported by the European Commission, the EVIDOS project started in November 2001
      with the broad goal of evaluating state of the art dosimetry techniques in
      representative workplaces of the nuclear industry. Seven European institutes
      joined efforts with end users at nuclear power plants, at fuel processing and
      reprocessing plants, and at transport and storage facilities. A comprehensive
      programme was devised to evaluate capabilities and limitations of standard and
      innovative personal dosemeters in relation to the mixed neutron-photon fields of
      concern to the nuclear industry. This paper describes the criteria behind the
      selection of dosimetry techniques and workplaces that were analysed, as well as
      the organisation of the measurement campaigns. Particular emphasis was placed on
      the evaluation of a variety of electronic personal dosemeters, either
      commercially available or previously developed by the partners. The estimates
      provided by these personal dosemeters were compared to reference values of dose
      equivalent quantities derived from spectrometry and fluence-to-dose equivalent
      conversion coefficients. Spectrometry was performed both with conventional
      multisphere and with some original instrumentation providing energy and direction
      resolution, based on silicon detectors and superheated drop detectors mounted on
      or in spherical moderators. The results were collected in a large, searchable
      database and are intended to be used in the harmonisation of dosimetric
      procedures for mixed radiation fields and for the approval of dosimetry services
      in Europe.

PMID- 17522044
TI  - In vivo functional analyses of the type II acyl carrier proteins of fatty acid
      biosynthesis.
AB  - Acyl carrier protein (ACP) is a key component of the fatty acid synthesis
      pathways of both type I and type II synthesis systems. A large number of
      structure-function studies of various type II ACPs have been reported, but all
      are in vitro studies that assayed function or interaction of mutant ACPs with
      various enzymes of fatty acid synthesis or transfer. Hence in these studies
      functional properties of various mutant ACPs were assayed with only a subset of
      the many ACP-interacting proteins, which may not give an accurate overall view of
      the function of these proteins in vivo. This is especially so because Escherichia
      coli ACP has been reported to interact with several proteins that have no known
      roles in lipid metabolism. We therefore tested a large number of mutant
      derivatives of E. coli ACP carrying single amino acid substitutions for their
      abilities to restore growth to an E. coli strain carrying a temperature-sensitive
      mutation in acpP, the gene that encodes ACP. Many of these mutant proteins had
      previously been tested in vitro thus providing data for comparison with our
      results. We found that several mutant ACPs containing substitutions of ACP
      residues reported previously to be required for ACP function in vitro support
      normal growth of the acpP mutant strain. However, several mutant proteins
      reported to be severely defective in vitro failed to support growth of the acpP
      strain in vivo (or supported only weak growth). A collection of ACPs from diverse
      bacteria and from three eukaryotic organelles was also tested. All of the
      bacterial ACPs tested restored growth to the E. coli acpP mutant strain except
      those from two related bacteria, Enterococcus faecalis and Lactococcus lactis.
      Only one of the three eukaryotic organellar ACPs allowed growth. Strikingly the
      ACP is that of the apicoplast of Plasmodium falciparum (the protozoan that causes
      malaria). The fact that an ACP from a such diverse organism can replace AcpP
      function in E. coli suggests that some of the protein-protein interactions
      detected for AcpP may be not be essential for growth of E. coli.

PMID- 17522045
TI  - Fatty acid transport protein 4 is the principal very long chain fatty acyl-CoA
      synthetase in skin fibroblasts.
AB  - Fatty acid transport protein 4 (FATP4) is a fatty acyl-CoA synthetase that
      preferentially activates very long chain fatty acid substrates, such as C24:0, to
      their CoA derivatives. To gain better insight into the physiological functions of
      FATP4, we established dermal fibroblast cell lines from FATP4-deficient wrinkle
      free mice and wild type (w.t.) mice. FATP4 -/- fibroblasts had no detectable
      FATP4 protein by Western blot. Compared with w.t. fibroblasts, cells lacking
      FATP4 had an 83% decrease in C24:0 activation. Peroxisomal degradation of C24:0
      was reduced by 58%, and rates of C24:0 incorporation into major phospholipid
      species (54-64% decrease), triacylglycerol (64% decrease), and cholesterol esters
      (58% decrease) were significantly diminished. Because these lipid metabolic
      processes take place in different subcellular organelles, we used
      immunofluorescence and Western blotting of subcellular fractions to investigate
      the distribution of FATP4 protein and measured enzyme activity in fractions from
      w.t. and FATP4 -/- fibroblasts. FATP4 protein and acyl-CoA synthetase activity
      localized to multiple organelles, including mitochondria, peroxisomes,
      endoplasmic reticulum, and the mitochondria-associated membrane fraction. We
      conclude that in murine skin fibroblasts, FATP4 is the major enzyme producing
      very long chain fatty acid-CoA for lipid metabolic pathways. Although FATP4
      deficiency primarily affected very long chain fatty acid metabolism, mutant
      fibroblasts also showed reduced uptake of a fluorescent long chain fatty acid and
      reduced levels of long chain polyunsaturated fatty acids. FATP4-deficient cells
      also contained abnormal neutral lipid droplets. These additional defects indicate
      that metabolic abnormalities in these cells are not limited to very long chain
      fatty acids.

PMID- 17522046
TI  - The SoxYZ complex carries sulfur cycle intermediates on a peptide swinging arm.
AB  - The bacterial Sox (sulfur oxidizing) system allows the utilization of inorganic
      sulfur compounds in energy metabolism. Central to this process is the SoxYZ
      complex that carries the pathway intermediates on a cysteine residue near the C
      terminus of SoxY. Crystal structures have been determined for Paracoccus
      pantotrophus SoxYZ with the carrier cysteine in the underivatized state,
      conjugated to the polysulfide mimic beta-mercaptoethanol, and as the sulfonate
      adduct pathway intermediate. The carrier cysteine is located on a peptide
      swinging arm and is bracketed on either side by diglycine dipeptides acting as
      molecular universal joints. This structure provides a novel solution to the
      requirement that the cysteine-bound intermediates be able to access and orient
      themselves within the active sites of multiple partner enzymes. Adjacent to the
      swinging arm there is a conserved, deep, apolar pocket into which the beta
      mercaptoethanol adduct extends. This pocket would be well suited to a role in
      protecting labile pathway intermediates from adventitious reactions.

PMID- 17522047
TI  - Structures of 5-methylthioribose kinase reveal substrate specificity and unusual
      mode of nucleotide binding.
AB  - The methionine salvage pathway is ubiquitous in all organisms, but metabolic
      variations exist between bacteria and mammals. 5-Methylthioribose (MTR) kinase is
      a key enzyme in methionine salvage in bacteria and the absence of a mammalian
      homolog suggests that it is a good target for the design of novel antibiotics.
      The structures of the apo-form of Bacillus subtilis MTR kinase, as well as its
      ADP, ADP-PO(4), AMPPCP, and AMPPCP-MTR complexes have been determined. MTR kinase
      has a bilobal eukaryotic protein kinase fold but exhibits a number of unique
      features. The protein lacks the DFG motif typically found at the beginning of the
      activation loop and instead coordinates magnesium via a DXE motif (Asp(250)
      Glu(252)). In addition, the glycine-rich loop of the protein, analogous to the
      "Gly triad" in protein kinases, does not interact extensively with the
      nucleotide. The MTR substrate-binding site consists of Asp(233) of the catalytic
      HGD motif, a novel twin arginine motif (Arg(340)/Arg(341)), and a semi-conserved
      W-loop, which appears to regulate MTR binding specificity. No lobe closure is
      observed for MTR kinase upon substrate binding. This is probably because the
      enzyme lacks the lobe closure/inducing interactions between the C-lobe of the
      protein and the ribosyl moiety of the nucleotide that are typically responsible
      for lobe closure in protein kinases. The current structures suggest that MTR
      kinase has a dissociative mechanism.

PMID- 17522048
TI  - A key role for orphan nuclear receptor liver receptor homologue-1 in activation
      of fatty acid synthase promoter by liver X receptor.
AB  - Liver X receptor (LXR) activates fatty acid synthase (FAS) gene expression
      through binding to a DR-4 element in the promoter. We show that a distinct
      nuclear receptor half-site 21 bases downstream of the DR-4 element is also
      critical for the response of FAS to LXR but is not involved in LXR binding to
      DNA. This half-site specifically binds liver receptor homologue-1 (LRH-1) in
      vitro and in vivo, and we show LRH-1 is required for maximal LXR responsiveness
      of the endogenous FAS gene as well as from promoter reporter constructs. We also
      demonstrate that LRH-1 stimulation of the FAS LXR response is blocked by the
      addition of small heterodimer partner (SHP) and that FAS mRNA is overexpressed in
      SHP knock-out animals, providing evidence that FAS is an in vivo target of SHP
      repression. Taken together, these findings identify the first direct lipogenic
      gene target of LRH-1/SHP repression and provide a mechanistic explanation for
      bile acid repression of FAS and lipogenesis recently reported by others.

PMID- 17522049
TI  - Atherogenic phospholipids attenuate osteogenic signaling by BMP-2 and parathyroid
      hormone in osteoblasts.
AB  - Cardiovascular disease, such as atherosclerosis, has been associated with reduced
      bone mineral density and fracture risk. A major etiologic factor in atherogenesis
      is believed to be oxidized phospholipids. We previously found that these
      phospholipids inhibit spontaneous osteogenic differentiation of marrow stromal
      cells, suggesting that they may account for the clinical link between
      atherosclerosis and osteoporosis. Currently, anabolic agents that promote bone
      formation are increasingly used as a new treatment for osteoporosis. It is not
      known, however, whether atherogenic phospholipids alter the effects of bone
      anabolic agents, such as bone morphogenetic protein (BMP)-2 and parathyroid
      hormone (PTH). Therefore we investigated the effects of oxidized 1-palmitoyl-2
      arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on osteogenic signaling
      induced by BMP-2 and PTH in MC3T3-E1 cells. Results showed that ox-PAPC
      attenuated BMP-2 induction of osteogenic markers alkaline phosphatase and
      osteocalcin. Ox-PAPC also inhibited both spontaneous and BMP-induced expression
      of PTH receptor. Consistently, pretreatment of cells with ox-PAPC inhibited PTH
      induced cAMP production and expression of immediate early genes Nurr1 and IL-6.
      Results from immunofluorescence and Western blot analyses showed that inhibitory
      effects of ox-PAPC on BMP-2 signaling were associated with inhibition of SMAD
      1/5/8 but not p38-MAPK activation. These effects appear to be due to ox-PAPC
      activation of the ERK pathway, as the ERK inhibitor PD98059 reversed ox-PAPC
      inhibitory effects on BMP-2-induced alkaline phosphatase activity, osteocalcin
      expression, and SMAD activation. These results suggest that atherogenic lipids
      inhibit osteogenic signaling induced by BMP-2 and PTH, raising the possibility
      that hyperlipidemia and atherogenic phospholipids may interfere with anabolic
      therapy.

PMID- 17522050
TI  - Possible role for intracellular cholesteryl ester transfer protein in adipocyte
      lipid metabolism and storage.
AB  - Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester (CE) and
      triglyceride (TG) between lipoproteins in plasma. However, short term suppression
      of CETP biosynthesis in cells alters cellular cholesterol homeostasis,
      demonstrating an intracellular role for CETP as well. The consequences of chronic
      CETP deficiency in lipid-storing cells normally expressing CETP have not been
      reported. Here, SW872 adipocytes stably expressing antisense CETP cDNA and
      synthesizing 20% of normal CETP were created. CETP-deficient cells had 4-fold
      more CE but an approximately 3-fold decrease in cholesterol biosynthesis. This
      phenotype of cholesterol overload is consistent with the observed 45% reduction
      in low density lipoprotein receptor and 2.5-fold increase in ABCA1 levels.
      However, cholesterol mass in CETP-deficient adipocytes was actually reduced.
      Strikingly, CETP-deficient adipocytes stored <50% of normal TG, principally
      reflecting reduced synthesis. The hydrolysis of cellular CE and TG in CETP
      deficient cells was reduced by >50%, although hydrolase/lipase activity was
      increased 3-fold. Notably, the incorporation of recently synthesized CE and TG
      into lipid storage droplets in CETP-deficient cells was just 40% of control,
      suggesting that these lipids are inefficiently transported to droplets where the
      hydrolase/lipase resides. The capacity of cellular CETP to transport CE and TG
      into storage droplets was directly demonstrated in vitro. Overall, chronic CETP
      deficiency disrupts lipid homeostasis and compromises the TG storage function of
      adipocytes. Inefficient CETP-mediated translocation of CE and TG from the
      endoplasmic reticulum to their site of storage may partially explain these
      defects. These studies in adipocytic cells strongly support a novel role for CETP
      in intracellular lipid transport and storage.

PMID- 17522051
TI  - A novel plant protein-disulfide isomerase involved in the oxidative folding of
      cystine knot defense proteins.
AB  - We have isolated a protein-disulfide isomerase (PDI) from Oldenlandia affinis
      (OaPDI), a coffee family (Rubiaceae) plant that accumulates knotted circular
      proteins called cyclotides. The novel plant PDI appears to be involved in the
      biosynthesis of cyclotides, since it co-expresses and interacts with the
      cyclotide precursor protein Oak1. OaPDI exhibits similar isomerase activity but
      greater chaperone activity than human PDI. Since domain c of OaPDI is predicted
      to have a neutral pI, we conclude that this domain does not have to be acidic in
      nature for PDI to be a functional chaperone. Its redox potential of -157 +/- 4 mV
      supports a role as a functional oxidoreductase in the plant. The mechanism of
      enzyme-assisted folding of plant cyclotides was investigated by comparing the
      folding of kalata B1 derivatives in the presence and absence of OaPDI. OaPDI
      dramatically enhanced the correct oxidative folding of kalata B1 at physiological
      pH. A detailed investigation of folding intermediates suggested that disulfide
      isomerization is an important role of the new plant PDI and is an essential step
      in the production of insecticidal cyclotides. The nucleotide sequence(s) reported
      in this paper have been submitted to the GenBank/EBI Data Bank with accession
      number(s) 911777.

PMID- 17522052
TI  - Rat liver peroxisomes after fibrate treatment. A survey using quantitative mass
      spectrometry.
AB  - Fibrates are known to induce peroxisome proliferation and the expression of
      peroxisomal beta-oxidation enzymes. To analyze fibrate-induced changes of complex
      metabolic networks, we have compared the proteome of rat liver peroxisomes from
      control and bezafibrate-treated rats. Highly purified peroxisomes were
      subfractionated, and the proteins of the matrix, peripheral, and integral
      membrane subfractions thus obtained were analyzed by matrix-assisted laser
      desorption ionization time-of-flight/time-of-flight mass spectrometry after
      labeling of tryptic peptides with the iTRAQ reagent. By means of this
      quantitative technique, we were able to identify 134 individual proteins,
      covering most of the known peroxisomal proteome. Ten predicted new open reading
      frames were verified by cDNA cloning, and seven of them could be localized to
      peroxisomes by immunocytochemistry. Moreover, quantitative mass spectrometry
      substantiated the induction of most of the known peroxisome proliferator
      activated receptor alpha-regulated peroxisomal proteins upon treatment with
      bezafibrate, documenting the suitability of the iTRAQ procedure in larger scale
      experiments. However, not all proteins reacted to a similar extent but exerted a
      fibrate-specific induction scheme showing the variability of peroxisome
      proliferator-activated receptoralpha-transmitted responses to specific ligands.
      In view of our data, rat hepatic peroxisomes are apparently not specialized to
      sequester very long chain fatty acids (C22-C26) but rather metabolize
      preferentially long chain fatty acids (C16-18).

PMID- 17522053
TI  - Aquaporin-1 channel function is positively regulated by protein kinase C.
AB  - Aquaporin-1 (AQP1) channels contribute to osmotically induced water transport in
      several organs including the kidney and serosal membranes such as the peritoneum
      and the pleura. In addition, AQP1 channels have been shown to conduct cationic
      currents upon stimulation by cyclic nucleotides. To date, the short term
      regulation of AQP1 function by other major intracellular signaling pathways has
      not been studied. In the present study, we therefore investigated the regulation
      of AQP1 by protein kinase C. AQP1 wild type channels were expressed in Xenopus
      oocytes. Water permeability was assessed by hypotonic challenges. Activation of
      protein kinase C (PKC) by 1-oleoyl-2-acetyl-sn-glycerol (OAG) induced a marked
      increase of AQP1-dependent water permeability. This regulation was abolished in
      mutated AQP1 channels lacking both consensus PKC phosphorylation sites Thr(157)
      and Thr(239) (termed AQP1 DeltaPKC). AQP1 cationic currents measured with double
      electrode voltage clamp were markedly increased after pharmacological activation
      of PKC by either OAG or phorbol 12-myristate 13-acetate. Deletion of either
      Thr(157) or Thr(239) caused a marked attenuation of PKC-dependent current
      increases, and deletion of both phosphorylation sites in AQP1 DeltaPKC channels
      abolished the effect. In vitro phosphorylation studies with synthesized peptides
      corresponding to amino acids 154-168 and 236-250 revealed that both Thr(157) and
      Thr(239) are phosphorylated by PKC. Upon stimulation by cyclic nucleotides, AQP1
      wild type currents exhibited a strong activation. This regulation was not
      affected after deletion of PKC phosphorylation sites in AQP1 DeltaPKC channels.
      In conclusion, this is the first study to show that PKC positively regulates both
      water permeability and ionic conductance of AQP1 channels. This new pathway of
      AQP1 regulation is independent of the previously described cyclic nucleotide
      pathway and may contribute to the PKC stimulation of AQP1-modulated processes
      such as endothelial permeability, angiogenesis, and urine concentration.

PMID- 17522054
TI  - The N-terminal arm of the Helicobacter pylori Ni2+-dependent transcription factor
      NikR is required for specific DNA binding.
AB  - The Ni(2+)-dependent transcription factor NikR is widespread among microbes. The
      two experimentally characterized NikR orthologs, from Helicobacter pylori and
      Escherichia coli, display vastly different regulatory capabilities in response to
      increased intracellular Ni(2+). Here, we demonstrate that the nine-residue N
      terminal arm present in H. pylori NikR plays a critical role in the expanded
      regulatory capabilities of this NikR family member. Specifically, the N-terminal
      arm is required to inhibit NikR binding to low affinity and nonspecific DNA
      sequences and is also linked to a cation requirement for NikR binding to the nixA
      promoter. Site-directed mutagenesis and arm-truncation variants of NikR indicate
      that two residues, Asp-7 and Asp-8, are linked to the cation requirement for
      binding. Pro-4 and Lys-6 are required for maximal DNA binding affinity of the
      full-length protein to both the nixA and ureA promoters. The N-terminal arm is
      highly variable among NikR family members, and these results suggest that it is
      an adaptable structural feature that can tune the regulatory capabilities of NikR
      to the nickel physiology of the microbe in which it is found.

PMID- 17522055
TI  - Regulation of FOXO3a/beta-catenin/GSK-3beta signaling by 3,3'-diindolylmethane
      contributes to inhibition of cell proliferation and induction of apoptosis in
      prostate cancer cells.
AB  - Previous studies from our laboratory have shown anti-proliferative and pro
      apoptotic effects of 3,3'-diindolylmethane (DIM) through regulation of Akt and
      androgen receptor (AR) in prostate cancer cells. However, the mechanism by which
      DIM regulates Akt and AR signaling pathways has not been fully investigated. It
      has been known that FOXO3a and glycogen synthase kinase-3beta (GSK-3beta), two
      targets of activated Akt, interact with beta-catenin, regulating cell
      proliferation and apoptotic cell death. More importantly, FOXO3a, GSK-3beta, and
      beta-catenin are all AR coregulators and regulate the activity of AR, mediating
      the development and progression of prostate cancers. Here, we investigated the
      molecular effects of B-DIM, a formulated DIM with higher bioavailability, on
      Akt/FOXO3a/GSK-3beta/beta-catenin/AR signaling in hormone-sensitive LNCaP and
      hormone-insensitive C4-2B prostate cancer cells. We found that B-DIM
      significantly inhibited the phosphorylation of Akt and FOXO3a and increased the
      phosphorylation of beta-catenin, leading to the inhibition of cell growth and
      induction of apoptosis. We also found that B-DIM significantly inhibited beta
      catenin nuclear translocation. By electrophoretic mobility shift and chromatin
      immunoprecipitation assays, we found that B-DIM inhibited FOXO3a binding to the
      promoter of AR and promoted FOXO3a binding to the p27(KIP1) promoter, resulting
      in the alteration of AR and p27(KIP1) expression, the inhibition of cell
      proliferation, and the induction of apoptosis in both androgen-sensitive and 
      insensitive prostate cancer cells. These results suggest that B-DIM-induced cell
      growth inhibition and apoptosis induction are partly mediated through the
      regulation of Akt/FOXO3a/GSK-3beta/beta-catenin/AR signaling. Therefore, B-DIM
      could be a promising non-toxic agent for possible treatment of hormone-sensitive
      but most importantly hormone-refractory prostate cancers.

PMID- 17522056
TI  - Effects of the isoform-specific characteristics of ATF6 alpha and ATF6 beta on
      endoplasmic reticulum stress response gene expression and cell viability.
AB  - The endoplasmic reticulum (ER)-transmembrane proteins, ATF6 alpha and ATF6 beta,
      are cleaved during the ER stress response (ERSR). The resulting N-terminal
      fragments (N-ATF6 alpha and N-ATF6 beta) have conserved DNA-binding domains and
      divergent transcriptional activation domains. N-ATF6 alpha and N-ATF6 beta
      translocate to the nucleus, bind to specific regulatory elements, and influence
      expression of ERSR genes, such as glucose-regulated protein 78 (GRP78), that
      contribute to resolving the ERSR, thus, enhancing cell viability. We previously
      showed that N-ATF6 alpha is a rapidly degraded, strong transcriptional activator,
      whereas beta is a slowly degraded, weak activator. In this study we explored the
      molecular basis and functional impact of these isoform-specific characteristics
      in HeLa cells. Mutants in the transcriptional activation domain or DNA-binding
      domain of N-ATF6 alpha exhibited loss of function and increased expression, the
      latter of which suggested decreased rates of degradation. Fusing N-ATF6 alpha to
      the mutant estrogen receptor generated N-ATF6 alpha-MER, which, without tamoxifen
      exhibited loss-of-function and high expression, but in the presence of tamoxifen
      N-ATF6 alpha-MER exhibited gain-of-function and low expression. N-ATF6 beta
      conferred loss-of-function and high expression to N-ATF6 alpha, suggesting that
      ATF6 beta is an endogenous inhibitor of ATF6 alpha. In vitro DNA binding
      experiments showed that recombinant N-ATF6 beta inhibited the binding of
      recombinant N-ATF6 alpha to an ERSR element from the GRP78 promoter. Moreover,
      siRNA-mediated knock-down of endogenous ATF6 beta increased GRP78 promoter
      activity and GRP78 gene expression, as well as augmenting cell viability. Thus,
      the relative levels of ATF6 alpha and -beta, may contribute to regulating the
      strength and duration of ATF6-dependent ERSR gene induction and cell viability.

PMID- 17522057
TI  - SPARC regulates processing of procollagen I and collagen fibrillogenesis in
      dermal fibroblasts.
AB  - A characterization of the factors that control collagen fibril formation is
      critical for an understanding of tissue organization and the mechanisms that lead
      to fibrosis. SPARC (secreted protein acidic and rich in cysteine) is a counter
      adhesive protein that binds collagens. Herein we show that collagen fibrils in
      SPARC-null skin from mice 1 month of age were inefficient in fibril aggregation
      and accumulated in the diameter range of 60-70 nm, a proposed intermediate in
      collagen fibril growth. In vitro, procollagen I produced by SPARC-null dermal
      fibroblasts demonstrated an initial preferential association with cell layers, in
      comparison to that produced by wild-type fibroblasts. However, the collagen I
      produced by SPARC-null cells was not efficiently incorporated into detergent
      insoluble fractions. Coincident with an initial increase in cell association,
      greater amounts of total collagen I were present as processed forms in SPARC-null
      versus wild-type cells. Addition of recombinant SPARC reversed collagen I
      association with cell layers and decreased the processing of procollagen I in
      SPARC-null cells. Although collagen fibers formed on the surface of SPARC-null
      fibroblasts earlier than those on wild-type cells, fibers on SPARC-null
      fibroblasts did not persist. We conclude that SPARC mediates the association of
      procollagen I with cells, as well as its processing and incorporation into the
      extracellular matrix.

PMID- 17522058
TI  - Functional role of extracellular loop cysteine residues of the epithelial Na+
      channel in Na+ self-inhibition.
AB  - The epithelial Na(+) channel (ENaC) is typically formed by three homologous
      subunits (alpha, beta, and gamma) that possess a characteristic large
      extracellular loop (ECL) containing 16 conserved cysteine (Cys) residues. We
      investigated the functional role of these Cys residues in Na(+) self-inhibition,
      an allosteric inhibition of ENaC activity by extracellular Na(+). All 16 Cys
      residues within alpha and gamma ECLs and selected beta ECL Cys residues were
      individually mutated to alanine or serine residues. The Na(+) self-inhibition
      response of wild type and mutant channels expressed in Xenopus oocytes was
      determined by whole cell voltage clamp. Individual mutation of eight alpha (Cys
      1, -4, -5, -6, -7, -10, -13, or -16), one beta (Cys-7), and nine gamma (Cys-3, 
      4, -6, -7, -10, -11, -12, -13, or -16) residues significantly reduced the
      magnitude of Na(+) self-inhibition. Na(+) self-inhibition was eliminated by
      simultaneous mutations of either the last three alpha ECL Cys residues (Cys-14, 
      15, and -16) or Cys-7 within both alpha and gamma ECLs. By analyzing the Na(+)
      self-inhibition responses and the effects of a methanethiosulfonate reagent on
      channel currents in single and double Cys mutants, we identified five Cys pairs
      within the alphaECL (alphaCys-1/alphaCys-6, alphaCys-4/alphaCys-5, alphaCys
      7/alphaCys-16, alphaCys-10/alphaCys-13, and alphaCys-11/alphaCys-12) and one pair
      within the gammaECL (gammaCys-7/gammaCys-16) that likely form intrasubunit
      disulfide bonds. We conclude that approximately half of the ECL Cys residues in
      the alpha and gamma ENaC subunits are required to establish the tertiary
      structure that ensures a proper Na(+) self-inhibition response, likely by
      formation of multiple intrasubunit disulfide bonds.

PMID- 17522059
TI  - A novel form of 6-phosphofructokinase. Identification and functional relevance of
      a third type of subunit in Pichia pastoris.
AB  - Classically, 6-phosphofructokinases are homo- and hetero-oligomeric enzymes
      consisting of alpha subunits and alpha/beta subunits, respectively. Herein, we
      describe a new form of 6-phosphofructokinase (Pfk) present in several Pichia
      species, which is composed of three different types of subunit, alpha, beta, and
      gamma. The sequence of the gamma subunit shows no similarity to classic Pfk
      subunits or to other known protein sequences. In-depth structural and functional
      studies revealed that the gamma subunit is a constitutive component of Pfk from
      Pichia pastoris (PpPfk). Analyses of the purified PpPfk suggest a
      heterododecameric assembly from the three different subunits. Accordingly, it is
      the largest and most complex Pfk identified yet. Although, the gamma subunit is
      not required for enzymatic activity, the gamma subunit-deficient mutant displays
      a decreased growth on nutrient limitation and reduced cell flocculation when
      compared with the P. pastoris wild-type strain. Subsequent characterization of
      purified Pfks from wild-type and gamma subunit-deficient strains revealed that
      the allosteric regulation of the PpPfk by ATP, fructose 2,6-bisphosphate, and AMP
      is fine-tuned by the gamma subunit. Therefore, we suggest that the gamma subunit
      contributes to adaptation of P. pastoris to energy resources.

PMID- 17522060
TI  - PLAP-1/asporin, a novel negative regulator of periodontal ligament
      mineralization.
AB  - Periodontal ligament-associated protein-1 (PLAP-1)/asporin is a recently
      identified novel member of the small leucine-rich repeat proteoglycan family.
      PLAP-1/asporin is involved in chondrogenesis, and its involvement in the
      pathogenesis of osteoarthritis has been suggested. We report that PLAP-1/asporin
      is also expressed specifically and predominantly in the periodontal ligament
      (PDL) and that it negatively regulates the mineralization of PDL cells. In situ
      hybridization analysis revealed that PLAP-1/asporin was expressed specifically
      not only in the PDL of an erupted tooth but also in the dental follicle, which is
      the progenitor tissue of the PDL during tooth development. Overexpression of PLAP
      1/asporin in mouse PDL-derived clone cells interfered with both naturally and
      bone morphogenetic protein 2 (BMP-2)-induced mineralization of the PDL cells. On
      the other hand, knockdown of PLAP-1/asporin transcript levels by RNA interference
      enhanced BMP-2-induced differentiation of PDL cells. Furthermore co
      immunoprecipitation assays showed a direct interaction between PLAP-1/asporin and
      BMP-2 in vitro, and immunohistochemistry staining revealed the co-localization of
      PLAP-1/asporin and BMP-2 at the cellular level. These results suggest that PLAP
      1/asporin plays a specific role(s) in the periodontal ligament as a negative
      regulator of cytodifferentiation and mineralization probably by regulating BMP-2
      activity to prevent the periodontal ligament from developing non-physiological
      mineralization such as ankylosis.

PMID- 17522061
TI  - Renin-angiotensin system haplotypes and the risk of myocardial infarction and
      stroke in pharmacologically treated hypertensive patients.
AB  - The products of the renin-angiotensin system (RAS) play an important role in the
      pathogenesis of cardiovascular disease. Studies examining RAS gene variants and
      cardiovascular disease have focused on single-nucleotide polymorphisms (SNPs)
      rather than haplotypes, which better characterize the patterns of genetic
      variation. The authors conducted a population-based, case-control study at Group
      Health (Seattle, Washington) between 1995 and 1999 to determine whether common
      haplotypes in the angiotensinogen gene (AGT), the renin gene, the angiotensin
      converting enzyme gene, and the angiotensin II receptor type 1 and receptor type
      2 genes were associated with the risk of myocardial infarction and stroke among
      pharmacologically treated hypertensive patients. SNP discovery was done using 23
      European-origin samples. Thirty tagSNPs (the minimum sets of SNPs that capture
      most of the haplotype diversity within a block) were genotyped in cases and
      controls. Haplotypes were inferred using the program PHASE
      (http://www.stat.washington.edu/stephens/software.html). The authors used
      weighted logistic regression to estimate associations and conducted a permutation
      test to estimate the probability of a chance finding. AGT haplotype B was
      associated with the risk of myocardial infarction (odds ratio = 1.58, 95%
      confidence interval: 1.06, 2.35); however, results were not statistically
      significant given the number of tests performed (permutation p = 0.17). In this
      case-control study, RAS gene haplotypes were not significantly associated with
      increased risks of myocardial infarction or stroke.

PMID- 17522062
TI  - Complex engagement of DNA damage response pathways in human cancer and in lung
      tumor progression.
AB  - Tumor initiation and progression provide a multitude of occasions for the
      generation of DNA damage and the consequent activation of the DNA damage response
      (DDR) pathway. DDR signaling involves the engagement of key factors such as ATM,
      CHK2, 53BP1 and the phosphorylation of histone H2AX (gamma-H2AX). The systematic
      study of DDR in human tumors and normal tissues by high-throughput tissue
      microarrays revealed that ATM and gamma-H2AX were engaged in cancer but the
      extent of their activation was strongly affected by the organ and cell type
      involved, whereas 53BP1 loss was the most consistent feature among the tumor
      studied. Unexpectedly, we also observed activated DDR markers in morphologically
      normal tissues, also in association with inflammation. Analysis of the dynamic
      engagement of DDR along the different stages of lung tumorigenesis showed that
      53BP1 loss occurs early at the transition from normal to dysplastic change
      whereas the activated forms of ATM and CHK2, but not gamma-H2AX, initially
      accumulate in pre-invasive lesions and are then lost during tumor progression. In
      individual lung tumors, the activation of ATM, CHK2 and the presence of 53BP1
      were consistently correlated, whereas gamma-H2AX did not correlate with activated
      ATM. Finally, the study of associations between critical clinicopathological
      parameters and activated DDR factors highlighted a statistically meaningful
      correlation between reduced local tumor extension and the phosphorylation of ATM,
      CHK2 and the presence of 53BP1, whereas no significant correlations with
      parameters such as survival or relapse of early-stage lung carcinomas were found.

PMID- 17522063
TI  - Adenomatous polyposis coli-mediated hypersensitivity of mouse embryonic
      fibroblast cell lines to methylmethane sulfonate treatment: implication of base
      excision repair pathways.
AB  - The role of adenomatous polyposis coli (APC) has been implicated in various
      cellular functions including cell migration, cell-cell adhesion, cell cycle
      control, chromosomal segregation and apoptosis. Recently, we discovered a novel
      role of APC in DNA base excision repair (BER) and showed that APC interacts with
      DNA polymerase beta (Pol-beta) and flap endonuclease 1 and interferes long-patch
      base excision repair (LP-BER) by blocking strand displacement synthesis. Many
      times, the chemotherapeutic drugs induce DNA alkylation damage, which is
      primarily repaired by the BER pathway. Thus, the efficacy of such drugs can be
      increased by APC resulting in the blockage of LP-BER. In the present study, we
      tested this hypothesis by using isogenic wild-type and Pol-beta-knockout mouse
      embryonic fibroblast (MEF) cell lines in which the Apc gene was knocked down by
      the small interfering RNA technique and treated with methylmethane sulfonate
      (MMS). The MEF-Apc(WT)/Polbeta-/- cells were hypersensitive to MMS treatment
      compared with the MEF-Apc(WT)/Polbeta+/+ cells. However, once the Apc gene was
      knocked down, these cells became more resistant to MMS treatment, suggesting that
      the MMS-induced hypersensitivity was associated with Apc. We then determined
      whether the hypersensitivity of MEF-Apc(WT)/Polbeta-/- and MEF-Apc(WT)/Polbeta+/+
      cell lines were due to decreased Pol-beta-independent and Pol-beta-dependent LP
      BER pathways, respectively. The results of in vivo and in vitro LP-BER assays
      supported our findings. Furthermore, Apc-mediated hypersensitivity to MMS
      treatment was correlated with increased apoptosis of MEF-Apc(WT)/Polbeta-/- and
      MEF-Apc(WT)/Polbeta+/+ as compared with MEF-Apc(KD)/Polbeta-/- and MEF
      Apc(KD)/Polbeta+/+ cells. These results suggest that an increased level of Apc
      can increase the efficacy of DNA-alkylating drugs used as a curative therapy.

PMID- 17522064
TI  - Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and
      turmerones differentially regulate anti-inflammatory and anti-proliferative
      responses through a ROS-independent mechanism.
AB  - Curcumin, a component of turmeric (Curcuma longa), has been shown to exhibit
      chemopreventive activity. Whether analogs of curcumin (Cur), such as
      demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), tetrahydrocurcumin (THC)
      and turmerones, modulate inflammatory signaling and cell proliferation signaling
      to same extent as curcumin was investigated. The results indicate that the
      relative potency for suppression of tumor necrosis factor (TNF)-induced nuclear
      factor-kappaB (NF-kappaB) activation was Cur > DMC > BDMC; thus suggesting the
      critical role of methoxy groups on the phenyl ring. THC, which lacks the
      conjugated bonds in the central seven-carbon chain, was completely inactive for
      suppression of the transcription factor. Turmerones also failed to inhibit TNF
      induced NF-kappaB activation. The suppression of NF-kappaB activity correlated
      with inhibition of NF-kappaB reporter activity and with down-regulation of
      cyclooxygenase-2, cyclin D1 and vascular endothelial growth factor, all regulated
      by NF-kappaB. In contrast to NF-kappaB activity, the suppression of proliferation
      of various tumor cell lines by Cur, DMC and BDMC was found to be comparable;
      indicating the methoxy groups play minimum role in the growth-modulatory effects
      of curcumin. THC and turmerones were also found to be active in suppression of
      cell growth but to a much lesser extent than curcumin, DMC and BDMC. Whether
      suppression of NF-kappaB or cell proliferation, no relationship of any of the
      curcuminoid was found with reactive oxygen species (ROS) production. Overall, our
      results demonstrated that different analogs of curcumin present in turmeric
      exhibit variable anti-inflammatory and anti-proliferative activities, which do
      not correlate with their ability to modulate the ROS status.

PMID- 17522065
TI  - Potent carcinogenicity of cigarette smoke in mice exposed early in life.
AB  - In spite of the dominant role of cigarette smoke (CS) in cancer epidemiology, all
      studies performed during the past 60 years have shown that this complex mixture
      is either negative or weakly tumorigenic in experimental animals. We implemented
      studies aimed at evaluating whether exposure of mice early in life may enhance
      susceptibility to CS carcinogenicity. A total of 98 newborn Swiss albino mice
      were either untreated (controls) or received a subcutaneous injection of
      benzo(a)pyrene [B(a)P] (positive control) or were exposed whole-body to
      mainstream cigarette smoke (MCS) for 120 days, starting within 12 h after birth.
      Complete necropsy and histopathological analyses were performed at periodical
      intervals. In contrast with the lack of lung tumors in controls, MCS-exposed mice
      developed microscopically detectable tumors, starting only 75 days after birth
      and reaching an overall incidence of 78.3% after 181-230 days. The mean lung
      tumor multiplicities were 6.1 and 13.6 tumors per mouse in males and females,
      respectively, showing a significant intergender difference. Most tumors were
      microadenomas or adenomas, but 18.4% of the mice additionally had malignant lung
      cancer. MCS also induced bronchial and alveolar epithelial hyperplasia, and blood
      vessel proliferation. Furthermore, malignant tumors, some of which may have a
      metastatic origin, were detected in the urinary tract and liver of MCS-exposed
      mice. A somewhat different spectrum of tumors was observed in B(a)P-treated mice.
      In conclusion, MCS is a potent and broad spectrum carcinogen in mice when
      exposure starts early in life, covering stages of life corresponding to neonatal,
      childhood and adolescence periods in humans. This animal model will be useful to
      explore the mechanisms involved in CS-induced carcinogenesis and to investigate
      the protective effects of dietary agents and chemopreventive drugs.

PMID- 17522066
TI  - Hair dye use, genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and
      risk of non-Hodgkin lymphoma.
AB  - BACKGROUND: Several previous studies have found non-Hodgkin lymphoma (NHL) risk
      to be associated with hair dye use, particularly use of permanent, dark colors
      and use before 1980, when hair dye formulations changed. METHODS: We examined NHL
      risk in relation to reported hair dye use among 1,321 cases and 1,057 controls
      from a US population-based multi-center study. DNA was extracted from blood or
      buccal cells to identify genetic variation in N-acetyltransferase 1 (NAT1) and 2
      (NAT2), which encode enzymes that metabolize aromatic amine compounds found in
      hair dyes. RESULTS: Among women, 509 cases and 413 controls reported hair dye use
      [odds ratio (OR) = 1.2; 95% confidence interval (95% CI) = 0.9, 1.6]. Risk
      estimates were higher for use before 1980 than for use in 1980 or later,
      particularly for use of permanent, intense tone (black, dark brown, dark blonde)
      products (<1980-OR = 1.6; 95% CI 0.9, 2.7; >or=1980-OR = 0.6; 95% CI 0.4, 1.1).
      Risk estimates were increased for women who used permanent, intense tone products
      before 1980 if they had the rapid/intermediate NAT2 phenotype (OR = 3.3; 95% CI
      1.3, 8.6) or the NAT1 10 allele (OR = 2.5; 95% CI 0.9, 7.6), but not if they were
      slow NAT2 acetylators (OR = 1.5; 95% CI 0.6, 3.6) or had no copies of the NAT1 10
      allele (OR = 1.5; 95% CI 0.7, 3.3). NHL risk was not increased among women who
      began hair dye use after 1980 or among men. CONCLUSION: Our results support
      previous research demonstrating elevated NHL risk among women who used dark color
      or intense tone permanent hair dyes before 1980. We present the first evidence
      suggesting that this risk may differ by genetic variation in NAT1 and NAT2.

PMID- 17522067
TI  - Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells
      through activation of caspase-dependent and caspase-independent pathways.
AB  - Polyphenols from fruits and vegetables exhibit anticancer properties both in
      vitro and in vivo and specialty potatoes are an excellent source of dietary
      polyphenols, including phenolic acids and anthocyanins. This study investigated
      the effects of specialty potato phenolics and their fractions on LNCaP (androgen
      dependent) and PC-3 (androgen independent) prostate cancer cells. Phenolic
      extracts from four specialty potato cultivars CO112F2-2, PATX99P32-2, ATTX98462-3
      and ATTX98491-3 and organic acid, phenolic acid and anthocyanin fractions (AF)
      were used in this study. CO112F2-2 cultivar extracts and their AF at 5 mug
      chlorogenic acid eq/ml were more active and inhibited cell proliferation and
      increased the cyclin-dependent kinase inhibitor p27 levels in both LNCaP and PC-3
      cells. Potato extract and AF induced apoptosis in both the cells and, however,
      the effects were cell context dependent. Cell death pathways induced by potato
      extract and AF were associated with mitogen-activated protein kinase and c-jun N
      terminal kinase activation and these kinases activated caspase-independent
      apoptosis through nuclear translocation of endonuclease G (Endo G) and apoptosis
      inducing factor in both cell lines. Induction of caspase-dependent apoptosis was
      also kinase dependent but was observed only in LNCaP cells. Kinase inhibitors
      reversed this nuclear translocation of endonuclease G and apoptosis-inducing
      factor. This is the first report showing that the cytotoxic activities of potato
      extract/AF in cancer cells were due to activation of caspase-independent
      apoptosis. Current studies are focused on identifying individual components of
      the AF responsible for the induction of cell death pathways in prostate and other
      cancer cell lines and developing potato cultivars that overexpress these active
      compounds.

PMID- 17522068
TI  - Promoter hypermethylation is associated with current smoking, age, gender and
      survival in bladder cancer.
AB  - Hypermethylation of tumor suppressor genes is central to the pathogenesis of
      human malignancy, yet this alteration's etiology remains unclear, and its
      clinical impact has not yet been studied using an approach that can yield
      directly generalizable results. Therefore, we sought to examine both of these
      issues in bladder cancer, seeking to understand the characteristics of
      epidemiologically well-defined patient tumors with differing levels of
      methylation silencing. We analyzed epigenetic silencing of 16 genes in a
      population-based incident case series of 331 bladder transitional cell
      carcinomas. We utilized a novel item response theory (IRT) model, to examine, in
      an unbiased fashion, the relationship of patient characteristics, carcinogen
      exposure history and tumor characteristics with the underlying propensity for
      gene hypermethylation. Age, male gender and current cigarette smoking were
      significantly positively associated with the methylation latent trait. Promoter
      hypermethylation as a latent trait significantly predicted both non-invasive/high
      grade and invasive stage disease and was also significantly associated with
      survival, with each unit increase in the latent trait resulting in a 30% increase
      in the risk of death. This work, studying all stages and grades of incident
      bladder cancer, provides definitive evidence that carcinogen exposures play a
      critical role in selecting these alterations in tumorous clones and that
      epigenetic silencing is a strong and significant predictor of tumor stage and
      overall patient survival. Finally, our novel approach provides insight into the
      etiology of promoter hypermethylation, suggesting that selected, carcinogen
      exposed individuals have a greater propensity for hypermethylation that is
      associated with more aggressive, fatal disease.

PMID- 17522069
TI  - Direct evidence for the critical role of NFAT3 in benzo[a]pyrene diol-epoxide
      induced cell transformation through mediation of inflammatory cytokine TNF
      induction in mouse epidermal Cl41 cells.
AB  - Nuclear factor of activated T cell (NFAT)-3 is a member of the transcription
      factor NFAT family, which has been demonstrated to be responsible for the up
      regulation of the pro-inflammatory cytokine tumor necrosis factor (TNF) in the
      immune system. Our most recent studies have also shown that TNF is able to induce
      cell transformation in mouse epidermal Cl41 cells by induction of cyclooxygenase
      2 (COX-2) expression. To provide direct evidence for NFAT3 in the environmental
      carcinogen-caused carcinogenic effect, (+/-)-benzo[a]pyrene-7,8-diol-9,10-epoxide
      (B[a]PDE), an ultimate environmental carcinogen metabolized from benzo[a]pyrene,
      was utilized. We found that exposure of Cl41 cells to B[a]PDE was able to induce
      cell transformation in Cl41 cells, while specific knock-down of NFAT3 resulted in
      the dramatic inhibition of this cell transformation. The tumorigenicity of
      B[a]PDE-caused transformed cells was confirmed in nude mice, whereas the tumor
      formation of B[a]PDE-treated NFAT3 small interference RNA (siRNA) knock-down
      cells was significantly reduced. Further studies showed that the role of NFAT3 in
      B[a]PDE-caused cell transformation was mediated by up-regulation of its
      downstream targeted gene TNF. This conclusion was based on the findings that
      inhibition of NFAT3 activation by either FK506 or NFAT3 siRNA dramatically down
      regulated the TNF induction upon B[a]PDE exposure, and that knock-down of TNF by
      its specific siRNA also led to abrogation of B[a]PDE-induced cell transformation
      in Cl41 cells and their tumorigenicity in nude mice. Collectively, these results
      provide direct evidence for the important role of NFAT3 activation in B[a]PDE
      induced cell transformation by up-regulation of TNF expression in mouse epidermal
      Cl41 cells, further suggesting that B[a]PDE may exert its tumor promotion effect
      on skin carcinogenesis, at least partially, by inducing TNF expression.

PMID- 17522070
TI  - Acute hepatotoxicity: a predictive model based on focused illumina microarrays.
AB  - Drug-induced hepatotoxicity is a major issue for drug development, and
      toxicogenomics has the potential to predict toxicity during early toxicity
      screening. A bead-based Illumina oligonucleotide microarray containing 550 liver
      specific genes has been developed. We have established a predictive screening
      system for acute hepatotoxicity by analyzing differential gene expression
      profiles of well-known hepatotoxic and nonhepatotoxic compounds. Low and high
      doses of tetracycline, carbon tetrachloride (CCL4), 1-naphthylisothiocyanate
      (ANIT), erythromycin estolate, acetaminophen (AAP), or chloroform as
      hepatotoxicants, clofibrate, theophylline, naloxone, estradiol, quinidine, or
      dexamethasone as nonhepatotoxic compounds, were administered as a single dose to
      male Sprague-Dawley rats. After 6, 24, and 72 h, livers were taken for
      histopathological evaluation and for analysis of gene expression alterations. All
      hepatotoxic compounds tested generated individual gene expression profiles. Based
      on leave-one-out cross-validation analysis, gene expression profiling allowed the
      accurate discrimination of all model compounds, 24 h after high dose treatment.
      Even during the regeneration phase, 72 h after treatment, CCL4, ANIT, and AAP
      were predicted to be hepatotoxic, and only these three compounds showed
      histopathological changes at this time. Furthermore, we identified 64 potential
      marker genes responsible for class prediction, which reflected typical
      hepatotoxicity responses. These genes and pathways, commonly deregulated by
      hepatotoxicants, may be indicative of the early characterization of
      hepatotoxicity and possibly predictive of later hepatotoxicity onset. Two unknown
      test compounds were used for prevalidating the screening test system, with both
      being correctly predicted. We conclude that focused gene microarrays are
      sufficient to classify compounds with respect to toxicity prediction.

PMID- 17522071
TI  - A review of large granular lymphocytic leukemia in Fischer 344 rats as an initial
      step toward evaluating the implication of the endpoint to human cancer risk
      assessment.
AB  - Large granular lymphocyte leukemia (LGLL) is a common fatal disease in aging F344
      rats. The current understanding of rat LGLL and a search for mechanistic
      data/correlations to human leukemia were examined with the goal of improving
      evaluation of the LGLL endpoint in cancer bioassays as it relates to human cancer
      risk assessments. The exact cell of origin of the F344 rat LGLL is not fully
      resolved, although natural killer (NK) cell characteristics were demonstrated in
      most, if not all cases. Similarities between rat LGLL and a rare human NK-LGLL
      exist, invalidating claims of no human counterpart, although the underlying
      etiopathogenesis may be different. There is insufficient data to establish a mode
      of action of chemical-induced rat LGLL. Evaluation of the National Toxicology
      Program database revealed only 34 substances (out of over 500 studied) that were
      possibly associated with increased incidences of LGLL. Of these, only five
      produced definitive LGLL effects in both sexes; the remaining 29 produced single
      sex responses and/or only "equivocal" associations with LGLL. Trends of
      increasing background/variability in LGLL incidence and its modulation by
      extraneous factors (e.g., corn oil gavage) are key confounders in interpretation.
      Given that LGLL is a common tumor in control F344 rats, interpretations of
      bioassays can be improved by increasing the statistical stringency (e.g., p<0.01
      over traditional p<0.05), as an indicator of possible carcinogenic effects, but
      that alone would be insufficient evidence for declaring treatment-related
      increases. Thus, it was concluded that the evaluation of possible chemically
      related increases in rat LGLL utilize a "weight-of-evidence" approach.

PMID- 17522072
TI  - Uranium induces apoptosis and is genotoxic to normal rat kidney (NRK-52E)
      proximal cells.
AB  - Uranium (U) is a heavy metal used in the nuclear industry and for military
      applications. U compounds are toxic. Their toxicity is mediated either by their
      radioactivity or their chemical properties. Mammalian kidneys and bones are the
      main organs affected by U toxicity. Although the most characteristic response to
      U exposure is renal dysfunction, little information is available on the
      mechanisms of its toxicity at the molecular level. This report studied the
      genotoxicity of U. Apoptosis induction in normal rat kidney (NRK-52(E)) proximal
      cells was investigated as a function of exposure time or concentrations (0
      800microM). In parallel, DNA damage was evaluated by several methods. In order to
      distinguish between the intrinsic and the extrinsic pathways of apoptosis,
      caspases-8, -9, -10 assays were conducted and the mitochondrial membrane
      potential was measured. Three methods were selected for their complementarities
      in the detection of genetic lesions. The comet assay was used for the detection
      of primary lesions of DNA. gamma-H2AX immunostaining was achieved to detect DNA
      double-strand breaks. The micronucleus assay was used to detect chromosomic
      breaks or losses. DNA damage and apoptosis were observed in a concentration
      dependent manner. This study demonstrated that U is genotoxic from 300microM and
      induces caspase-dependent apoptosis cell death from 200microM mainly through the
      intrinsic pathway in NRK-52(E) cells. These results suggest that the DNA damage
      caused by U is reversible at low concentration (200-400microM) but becomes
      irreversible and leads to cell death for higher concentrations (500-800microM).

PMID- 17522073
TI  - The contrasting effects of ad libitum and restricted feeding of a diet very high
      in saturated fats on sex ratio and metabolic hormones in mice.
AB  - Skewing of the sex ratio towards males occurs among pups born to mice fed a very
      high saturated fat (VHF) diet. In the present study, we tested whether the fat
      content of the VHF diet rather than the number of calories consumed is
      responsible for this effect. Eight-week-old NIH Swiss mice were placed on the VHF
      diet either ad libitum (VHF) or in a restricted manner (VHF-R). The VHF-R mice
      gained weight at a similar rate to controls fed a standard chow diet. Mice were
      bred at 15 wk and subsequently at 26 wk and 35 wk of age. Overall, the VHF, VHF
      R, and control groups delivered 244, 242, and 274 pups, respectively, with male
      proportions of 0.60, 0.43, and 0.48, respectively. The pup sex ratios of the VHF
      group (favoring males) and VHF-R group (favoring females) each differed from 0.5
      (P < 0.01). The sex ratios also differed (P < 0.0001) between the VHF and control
      groups, and between the VHF and VHF-R groups. Within the diet groups, maternal
      body weight had no effect on sex ratio. Serum leptin concentrations among the
      dams were similar in the VHF and VHF-R groups but higher than in the control
      group, while the IGF1 and corticosterone levels were comparable in all three
      groups. Therefore, the atypical sex ratios of offspring born to dams on the VHF
      diet seem to be influenced by the amount of fat consumed. Since males fed the VHF
      diet had neither more Y-sperm nor sired more sons than daughters, the dietary
      effects are manifested exclusively through the female.

PMID- 17522074
TI  - Effect of insulin-like growth factor-binding protein 7 on steroidogenesis in
      granulosa cells derived from equine chorionic gonadotropin-primed immature rat
      ovaries.
AB  - Insulin-like growth factor (IGF)-binding protein (IGFBP) 7 is a secreted protein
      that regulates cellular proliferation, adhesion, and angiogenesis, and has low
      affinity for IGF compared with that of IGFBP1-IGFBP6. We sought to determine
      whether IGFBP7 is present in follicular fluid and to elucidate whether IGFBP7
      participates in the steroidogenesis of rat mature follicles. Follicular fluid and
      granulosa cells (GCs) were collected from immature rats 2 days after their
      treatment with equine chorionic gonadotropin (eCG). IGFBP7 protein was detected
      in the follicular fluid and the conditioned medium of cultured ovarian GCs by
      immunoblot analysis. When subconfluent GCs were cultured and treated with FSH and
      activin, coincubation with FSH and activin markedly increased GC expression of
      Cyp19a1 (aromatase) mRNA and 17beta-estradiol (E(2)) secretion. The addition of
      recombinant murine IGFBP7 to these cultures decreased in the activin-enhanced,
      FSH-stimulated Cyp19a1 mRNA levels in the cells and suppressed the 17beta-E(2)
      levels in the culture medium. Treatment of GCs with Igfbp7-specific small
      interfering RNA (siRNA), which knocked down Igfbp7 expression, increased the FSH
      stimulated levels of Cyp19a1 but not Cyp11a1 expression. Basal and FSH-stimulated
      17beta-E(2) secretion into the culture medium was also enhanced by Igfbp7 siRNA.
      These results suggest that IGFBP7 suppresses estrogen production in GCs. These
      observations support the notion that this protein, which is secreted into the
      follicular fluid, may serve as an intraovarian factor that negatively regulates
      GC differentiation.

PMID- 17522075
TI  - Red deer cloned from antler stem cells and their differentiated progeny.
AB  - The significance of donor cell differentiation status for successful cloning by
      somatic cell nuclear transfer (SCNT) is unclear. Here, we cloned a new species,
      red deer (Cervus elaphus), from multipotent antler stem cells and their
      differentiated progeny. Cultured donor cell lines from male antlerogenic
      periosteum (AP) were left undifferentiated or chemically induced to initiate
      osteogenesis or adipogenesis. Based on their morphology and marker gene
      expression profile, donor cells were classified as undifferentiated AP cells,
      presumptive osteoblasts, or adipocytes. Adipocytes upregulated adipogenic markers
      procollagen type I alpha 2 (COL1A2), peroxisome proliferator-activated receptor
      gamma 2 (PPARG), and gylceraldehyde-3-phosphate dehydrogenase (GAPDH), and
      downregulated antlerogenic transcripts POU-domain class 5 transcription factor
      (POU5F1) and parathyroid hormone (PTH)-like hormone (PTHLH). Despite differences
      prior to NT, transcript abundance of donor-specific markers COL1A2, PPARG, GAPDH,
      and POU5F1 did not differ significantly in cloned blastocysts (P = 0.10, 0.50,
      0.61, and 0.16, respectively). However, donor cell and blastocyst expression
      levels were completely different for most genes analyzed, indicating their
      successful reprogramming. The type of donor cell used for NT (AP, bone, and fat
      cells), had no effect on in vitro development to blastocysts (93 [38%] of 248 vs.
      32 [44%] of 73 vs. 59 [32%] of 183, respectively). Likewise, development to
      weaning was not significantly different between the three cell types (2 [4%] of
      46 vs. 2 [29%] of 7 vs. 4 [13%] of 31, for AP vs. bone vs. fat, respectively).
      Microsatellite DNA analysis confirmed that the eight cloned red deer calves were
      genetically identical to the cells used for NT.

PMID- 17522076
TI  - Cattle cloned from increasingly differentiated muscle cells.
AB  - It has been postulated that mammalian nuclear transfer (NT) cloning efficiency is
      inversely correlated with donor cell differentiation status. To test this
      hypothesis, we compared genetically identical and increasingly differentiated
      donors within the myogenic lineage. Bovine male fetal muscle cells were cultured
      for 1-6 days in vitro. The proportion of cells displaying the following antigens
      was quantified by immunofluorescence microscopy: MYOD1, MYF5, PAX7, MYOG, DES,
      MYH, and 5-Bromo-2-deoxyuridine. Based on the antigen profile of both bulk
      populations and individually size-selected cells prepared for NT, donors serum
      starved for 1, 4, and 5 days were classified as myogenic precursors (MPCs),
      myotubes (MTs), and muscle-derived fibroblasts (MFs) with purities of 92%, 85%,
      and 99%, respectively. Expression of the following transcripts was measured by RT
      PCR in 1) cells selected for NT, 2) metaphase II oocytes, 3) NT couplets, 4) NT
      reconstructs, 5) NT two-cell embryos, and 6) NT blastocysts: MYOD1, MYF5, PAX7,
      MYOG, MYF6, ACTB, and 18S rRNA. Muscle-specific genes were silenced and remained
      undetectable up to the blastocyst stage, whereas housekeeping genes 18S and ACTB
      continued to be expressed. Differentiation status affected development to
      transferable embryos (118 [23%] of 520 vs. 93 [11%] of 873 vs. 66 [38%] of 174
      for MPC vs. MT vs. MF, respectively, P < 0.001). However, there were no
      significant differences in pregnancy rate and development to weaning between the
      cell types (pregnancy rate: 14 [64%] of 22 vs. 8 [35%] of 23 vs. 10 [45%] of 22,
      and development: 4 [18%] of 22 vs. 2 [9%] of 23 vs. 3 [14%] of 22 for MPC vs. MT
      vs. MF, respectively).

PMID- 17522077
TI  - Floral diversity and pollen transfer mechanisms in bird-pollinated Salvia
      species.
AB  - BACKGROUND AND AIMS: Bird-pollinated (ornithophilous) Salvia species (sages)
      transfer pollen either by means of a staminal lever mechanism or by immovable
      stamens. As the distribution of the two modes within the genus is not known, we
      present a survey of all ornithophilous sages. The main focus is given to floral
      diversity especially with respect to functional lever morphology. Thereby the
      hypothesis is tested that, due to a pollinator shift from bees to birds, the
      lever mechanism became unnecessary. METHODS: To get a general idea about the
      diversity of pollen transfer mechanisms, 186 ornithophilous Salvia species were
      classified according to the functional morphology of the stamen and the need for
      a lever movement. To test the functionality of the staminal levers and the
      fitting between flowers and birds the process of pollen transfer was examined by
      pollinator observations and tested by inserting museum skins and metal rods into
      fresh flowers. KEY RESULTS: The diversity of pollen transfer mechanisms is
      represented by eight case studies illustrating three main groups. In group I
      (approx. 50 %) the staminal lever mechanism is necessary to open access to nectar
      and to enable the transfer of pollen that is hidden in the upper lip. In group II
      (approx. 34 %) pollen is freely accessible and the lever mechanism is reduced in
      different ways and to different degrees. In group III (approx. 4 %) the lever
      works as in group I, but pollen is freely accessible as in II. The remaining
      approx. 13 % are not clearly classified. CONCLUSIONS: It is considered that the
      driving force behind the diverse modes of reduction is the necessity to increase
      the distance between nectar and pollen, thereby ensuring pollen deposition on the
      bird's feathered head. This is achieved several times in parallel by corolla
      elongation and/or exposure of the pollen-sacs. As soon as pollen is freely
      accessible, the lever movement loses its significance for pollination.

PMID- 17522078
TI  - Cumulative attendance, assessment and cancer detection rate over four screening
      rounds in five English breast-screening programmes: a retrospective study.
AB  - BACKGROUND: Data collection in the National Health Service Breast Screening
      Programme monitors performance in a different cohort of women each year. METHODS:
      This paper follows a single cohort study of 57,425 women (aged 50-53, when first
      invited) over four screening rounds to find: how many women attend screening and
      how often; how many were assessed; how many times they were assessed; and the
      number of cancers detected at each round. RESULTS: Average attendance in each
      round was 76.9% and has remained constant. Only 62% of women have attended all
      four rounds, but 89.9% have been screened at least once, the average number of
      attendances being 3.5. Average assessment rate decreased from 7.3 to 3.5%. A
      total of 11.3% of women were assessed once, 0.91% twice and 0.06% three times.
      Cancer detection rates have more than doubled from 3.3 per 1000 screened to 6.9.
      CONCLUSIONS: Current monitoring shows constant uptake over time, but when looking
      at a cohort of individual woman, a much larger percentage have 'ever' attended
      and a smaller number have attended all invitations. The chance of a woman being
      assessed at all, if she attends all four rounds, is 12.3%, which can be
      calculated by summating the recall rates in each round.

PMID- 17522079
TI  - Syncope in hypertrophic cardiomyopathy: mechanisms and consequences for
      treatment.
AB  - Hypertrophic cardiomyopathy (HCM) is an inherited disease with marked phenotypic
      variability that includes the extent of hypertrophy, the presence and severity of
      symptoms, and the natural history of the disease. Symptoms of impaired
      consciousness (syncope and pre-syncope) occur in approximately 15-25% of patients
      with hypertrophic cardiomyopathy (HCM). In young patients a history of recurrent
      syncope is associated with an increased risk of sudden death. Detailed
      investigations identify a probable mechanism in a minority of these, usually
      paroxysmal atrial fibrillation or ventricular tachycardia. In the majority,
      however, no likely mechanism is found despite extensive investigation. Although
      this may be the case, it is still of vital importance to exclude potentially
      treatable causes of syncope.

PMID- 17522080
TI  - Catheter ablation of multiple, surgically created, atrioventricular connections
      following Fontan-Bjork procedure.
AB  - An increased incidence of Wolff-Parkinson-White (WPW) syndrome with tricuspid
      atresia has been reported. Although atrioventricular accessory pathways may
      develop across suture lines after the Fontan-Bjork procedure, the presence of
      multiple acquired accessory pathways has only been described rarely. We report on
      a case of a female with tricuspid atresia who underwent the Fontan operation at 5
      years of age. One year later, she developed a WPW pattern. Narrow complex
      tachycardias started at the age of 18. An electrophysiological study revealed the
      presence of three accessory pathway connections at the surgical anastomosis
      level. All of them were successfully ablated and there were no recurrences.

PMID- 17522081
TI  - Early identification and treatment of PV re-connections: role of observation time
      and impact on clinical results of atrial fibrillation ablation.
AB  - AIMS: Circumferential pulmonary vein isolation (CPVI) has been reported to
      account for 30% of atrial fibrillation (AF) recurrence after initial ablation,
      and pulmonary vein (PV) re-connection accounts for about 80% of AF recurrence.
      There is no information in the literature whether early identification and
      treatment of acute PV conduction recovery during initial ablation has an impact
      on subsequent clinical results. The objective is to investigate the prevalence of
      acute PV conduction recovery during the observation time after PV isolation for
      paroxysmal AF, and to evaluate the impact of re-isolation treatment on clinical
      results. METHODS AND RESULTS: Ninety cases with paroxysmal AF (51 males, mean age
      of 56.4 +/- 12.3 years) were randomized to 3 groups to undergo CPVI. In Group A,
      there was no observation time post-ablation. In Group B, there was 30 min of
      observation time post-ablation. In Group C, there was 60 min of observation time
      post-ablation. All PV re-conduction was re-isolated at the end of the observation
      time. ECG and Holter monitors were used to evaluate the clinical effectiveness of
      ablation. All cases underwent the procedure successfully. The mean procedural
      time in Group A was significantly shorter than in Group B and Group C, but there
      was no significant difference on fluoroscopic time and PV isolation time among
      the three groups. In Group B, PV re-conduction occurred in 8 cases (25%) at 30
      min post-isolation, in 10 cases (31.2%) at 60 min post-isolation for left PVs,
      and in 6 cases (18.8%) at 30 min post-isolation for right PVs. In Group C, PV re
      conduction for left PVs occurred in 9 cases (30%) at 30 min post-isolation and in
      11 cases (36.7%) at 60 min post-isolation; for right PVs this occurred in 7 cases
      (23.3%) at 30 min post-isolation and in 8 cases (26.7%) at 60 min post-isolation.
      During a mean follow-up of 6.7 +/- 2.3 months, 17 cases (60.7%) in Group A, 27
      cases (84.3%) in Group B, and 26 cases (86.7%) in Group C had no recurrence of
      atrial tachyarrhythmias, P = 0.04. CONCLUSION: The prevalence of acute PV
      conduction recovery was about 30% after PV isolation, which mostly occurred
      within 30 min after initial isolation. Re-isolation of recovered PV conduction
      contributed to the improvement in the success rate of ablation for paroxysmal AF.

PMID- 17522082
TI  - Impacted left ventricular lead technique in cardiac resynchronization therapy.
AB  - Left ventricular (LV) lead dislodgement is a significant problem in cardiac
      resynchronization therapy and re-operation is required to rectify the situation.
      In this case report, we describe a new technique to stabilize an LV lead which is
      prone to dislodgement by impacting an inactive LV lead in the same cardiac vein.

PMID- 17522083
TI  - Legislated right for donor-insemination children to know their genetic origin: a
      study of parental thinking.
AB  - BACKGROUND: In Sweden, a child born as a result of donor insemination (DI) has
      the right to receive information both about the DI and the identity of the donor.
      The present study aimed to elucidate parents' thoughts regarding these
      possibilities, and whether, how and when they had told their offspring about the
      DI. An additional aim was to examine the parents' experiences of the attitudes of
      healthcare providers. METHODS: A follow-up study using semi-structured telephone
      interviews with 19 couples, including 19 women and 17 men. RESULTS: More than
      half of the parents (61%) had told all their child/ren about the DI, but almost
      everyone had told another person. Mean age for disclosure was 5 years for the
      first child. Reasons given for disclosure were to avoid accidental discovery, a
      desire for openness and a persons' fundamental right to know his/her genetic
      origin. Parents who did not intend to tell their child/ren considered DI a
      private matter and were afraid of other people's attitudes. Sixty-one percent of
      the parents had not yet told their children about the possibility of identifying
      the donor. Healthcare staff had impacted on the parents' thinking, and a majority
      of those who had been encouraged to tell their child/ren about the DI had done
      so. CONCLUSIONS: There was a discrepancy between the intentions of the
      legislation and how parents act in relation to them. To improve compliance, it is
      crucial to organize education, support and ethical discussion among
      professionals, and to offer parents, and parents-to-be, counselling, support and
      group sessions with other DI families.

PMID- 17522084
TI  - The genesis and spread of reassortment human influenza A/H3N2 viruses conferring
      adamantane resistance.
AB  - A dramatic rise in the frequency of resistance to adamantane drugs by influenza A
      (H3N2) viruses has occurred in recent years -- from approximately 2% to
      approximately 90% in multiple countries worldwide-and associated with a single
      S31N amino acid replacement in the viral matrix M2 protein. To explore the
      emergence and spread of these adamantane resistant viruses we performed a
      phylogenetic analysis of recently sampled complete A/H3N2 genome sequences.
      Strikingly, all adamantane resistant viruses belonged to a single lineage (the "N
      lineage") characterized by 17 amino acid replacements across the viral genome.
      Further, our analysis revealed that the genesis of the N-lineage was due to a 4+4
      segment reassortment event involving 2 distinct lineages of influenza A/H3N2
      virus. A subsequent study of hemagglutinin HA1 sequences suggested that the N
      lineage was circulating widely in Asia during 2005, and then dominated the
      Northern hemisphere 2005-2006 season in Japan and the USA. Given the infrequent
      use of adamantane drugs in many countries, as well as the decades of use in the
      US associated with little drug resistance, we propose that the globally
      increasing frequency of adamantane resistance is more likely attributable to its
      interaction with fitness-enhancing mutations at other genomic sites rather than
      to direct drug selection pressure. This implies that adamantanes may not be
      useful for treatment and prophylaxis against influenza viruses in the long term.
      More generally, these findings illustrate that drug selection pressure is not the
      sole factor determining the evolution and maintenance of drug resistance in human
      pathogens.

PMID- 17522085
TI  - Widespread intron loss suggests retrotransposon activity in ancient
      apicomplexans.
AB  - Several facets of spliceosomal intron in apicomplexans remain mysterious. First,
      intron numbers vary across species by 2 orders of magnitude, indicating massive
      intron loss and/or gain. Second, previous studies have shown very different
      evolutionary patterns over different timescales, with 100-fold higher rates of
      intron loss/gain between genera than within genera. Third, the timing and
      dynamics of nearly complete intron loss in Cryptosporidium species, as well as
      reasons for retention of the few remaining introns, remain unknown. We compared
      intron positions in 785 orthologous genes between 3 moderate to intron-rich
      apicomplexan species. We estimate that the Theileria-Plasmodium ancestor had 4.5
      times as many introns as modern Plasmodium species and 38% more than modern
      Theileria species, and that subsequent intron losses have outnumbered intron
      gains by 5.8 to 1 in Theileria and by some 56 to 1 in Plasmodium. Several
      patterns suggest that these intron losses occurred by recombination with reverse
      transcribed mRNAs. Intriguingly, this finding suggests significant
      retrotransposon activity in the lineages leading to both Theileria and
      Plasmodium, in contrast to the dearth of known retrotransposons and intron loss
      within modern species from both genera. We also compared genomes from
      Cryptosporidium parvum and C. hominis and found no evidence of ongoing intron
      loss, nor of intron gain. By contrast, Cryptosporidium introns are less
      evolutionary conserved with Toxoplasma than are introns from other apicomplexans;
      thus the few remaining introns are not simply indispensable ancestral introns.

PMID- 17522086
TI  - Plastid genome sequence of the cryptophyte alga Rhodomonas salina CCMP1319:
      lateral transfer of putative DNA replication machinery and a test of chromist
      plastid phylogeny.
AB  - Cryptophytes are a group of unicellular algae with chlorophyll c-containing
      plastids derived from the uptake of a secondary (i.e., eukaryotic) endosymbiont.
      Biochemical and molecular data indicate that cryptophyte plastids are derived
      from red algae, yet the question of whether or not cryptophytes acquired their
      red algal plastids independent of those in heterokont, haptophyte, and
      dinoflagellate algae is of long-standing debate. To better understand the origin
      and evolution of the cryptophyte plastid, we have sequenced the plastid genome of
      Rhodomonas salina CCMP1319: at 135,854 bp, it is the largest secondary plastid
      genome characterized thus far. It also possesses interesting features not seen in
      the distantly related cryptophyte Guillardia theta or in other red secondary
      plastids, including pseudogenes, introns, and a bacterial-derived gene for the
      tau/gamma subunit of DNA polymerase III (dnaX), the first time putative DNA
      replication machinery has been found encoded in any plastid genome. Phylogenetic
      analyses indicate that dnaX was acquired by lateral gene transfer (LGT) in an
      ancestor of Rhodomonas, most likely from a firmicute bacterium. A phylogenomic
      survey revealed no additional cases of LGT, beyond a noncyanobacterial type rpl36
      gene similar to that recently characterized in other cryptophytes and
      haptophytes. Rigorous concatenated analysis of 45 proteins encoded in 15 complete
      plastid genomes produced trees in which the heterokont, haptophyte, and
      cryptophyte (i.e., chromist) plastids were monophyletic, and heterokonts and
      haptophytes were each other's closest relatives. However, statistical support for
      chromist monophyly disappears when amino acids are recoded according to their
      chemical properties in order to minimize the impact of composition bias, and a
      significant fraction of the concatenate appears consistent with a sister-group
      relationship between cryptophyte and haptophyte plastids.

PMID- 17522087
TI  - Widespread positive selection in synonymous sites of mammalian genes.
AB  - Evolution of protein sequences is largely governed by purifying selection, with a
      small fraction of proteins evolving under positive selection. The evolution at
      synonymous positions in protein-coding genes is not nearly as well understood,
      with the extent and types of selection remaining, largely, unclear. A statistical
      test to identify purifying and positive selection at synonymous sites in protein
      coding genes was developed. The method compares the rate of evolution at
      synonymous sites (Ks) to that in intron sequences of the same gene after sampling
      the aligned intron sequences to mimic the statistical properties of coding
      sequences. We detected purifying selection at synonymous sites in approximately
      28% of the 1,562 analyzed orthologous genes from mouse and rat, and positive
      selection in approximately 12% of the genes. Thus, the fraction of genes with
      readily detectable positive selection at synonymous sites is much greater than
      the fraction of genes with comparable positive selection at nonsynonymous sites,
      i.e., at the level of the protein sequence. Unlike other genes, the genes with
      positive selection at synonymous sites showed no correlation between Ks and the
      rate of evolution in nonsynonymous sites (Ka), indicating that evolution of
      synonymous sites under positive selection is decoupled from protein evolution.
      The genes with purifying selection at synonymous sites showed significant
      anticorrelation between Ks and expression level and breadth, indicating that
      highly expressed genes evolve slowly. The genes with positive selection at
      synonymous sites showed the opposite trend, i.e., highly expressed genes had, on
      average, higher Ks. For the genes with positive selection at synonymous sites, a
      significantly lower mRNA stability is predicted compared to the genes with
      negative selection. Thus, mRNA destabilization could be an important factor
      driving positive selection in nonsynonymous sites, probably, through regulation
      of expression at the level of mRNA degradation and, possibly, also translation
      rate. So, unexpectedly, we found that positive selection at synonymous sites of
      mammalian genes is substantially more common than positive selection at the level
      of protein sequences. Positive selection at synonymous sites might act through
      mRNA destabilization affecting mRNA levels and translation.

PMID- 17522088
TI  - Quantifying the impact of protein tertiary structure on molecular evolution.
AB  - To investigate the evolutionary impact of protein structure, the experimentally
      determined tertiary structure and the protein-coding DNA sequence were collected
      for each of 1,195 genes. These genes were studied via a model of sequence change
      that explicitly incorporates effects on evolutionary rates due to protein
      tertiary structure. In the model, these effects act via the solvent accessibility
      environments and pairwise amino acid interactions that are induced by tertiary
      structure. To compare the hypotheses that structure does and does not have a
      strong influence on evolution, Bayes factors were estimated for each of the 1,195
      sequences. Most of the Bayes factors strongly support the hypothesis that protein
      structure affects protein evolution. Furthermore, both solvent accessibility and
      pairwise interactions among amino acids are inferred to have important roles in
      protein evolution. Our results also indicate that the strength of the
      relationship between tertiary structure and evolution has a weak but real
      correlation to the annotation information in the Gene Ontology database. Although
      their influences on rates of evolution vary among protein families, we find that
      the mean impacts of solvent accessibility and pairwise interactions are about the
      same.

PMID- 17522089
TI  - Proteomic study on X-irradiation-responsive proteins and ageing: search for
      responsible proteins for radiation adaptive response.
AB  - We investigated high- or low-dose irradiation-responsive proteins using
      proteomics on two-dimensional (2D) PAGE, and the effects of ageing on cell
      responses to radiation in variously aged rat astrocytes. After 5 Gy irradiation,
      the relative abundance of peroxiredoxin 2, an antioxidant enzyme, and latexin, an
      inhibitor of carboxypeptidase, increased. The induction of these proteins was
      suppressed by ageing, suggesting that the response to high-dose radiation
      decreased with ageing. The relative abundance of elongation factor 2 (EF-2)
      fragment increased 3 h and reduced 24 h after 0.1 Gy irradiation. Temporal
      enhancement of the EF-2 fragment due to low-dose irradiation was suppressed by
      ageing. Since radiation adaptive response in cultured astrocytes was observed 3 h
      but not 24 h after 0.1 Gy irradiation and suppressed by ageing as previously
      reported, alteration of the EF-2 fragment corresponded to the radiation adaptive
      response. We also examined phospho-protein profiles, resulting in the relative
      abundance of phospho-EF-1beta and phospho-beta-actin being altered by 0.1 Gy
      irradiation; however, ageing did not affect the alteration of phospho-EF-1beta
      and phospho-beta-actin, unlike the EF-2 fragment. The results suggested that the
      EF-2 fragment was a possible candidate for the protein responsible for the
      radiation adaptive response in cultured astrocytes.

PMID- 17522090
TI  - Unique peptide:N-glycanase of Caenorhabditis elegans has activity of protein
      disulphide reductase as well as of deglycosylation.
AB  - Peptide:N-glycanase (PNGase) is the enzyme responsible for de-N-glycosylation of
      misfolded glycoproteins in the cytosol. Here, we report the molecular
      identification and characterization of PNGase (png-1, F56G4.5) from
      Caenorhabditis elegans. This enzyme released both high mannose- and complex-type
      N-glycans from glycopeptides and denatured glycoproteins. Deglycosylation
      activity was inhibited by Zn(2+) and z-VAD-fmk, but not by EDTA. PNG-1 has a
      thioredoxin-like domain in addition to a transglutaminase domain, the core domain
      of PNGases, and exhibited protein disulphide reductase activity in vitro. Our
      biochemical studies revealed that PNG-1 is a unique bifunctional protein
      possessing two enzyme activities.

PMID- 17522091
TI  - Transgenic mice expressing a fully nontoxic diphtheria toxin mutant, not CRM197
      mutant, acquire immune tolerance against diphtheria toxin.
AB  - We previously developed a method termed "toxin receptor-mediated cell knockout"
      (TRECK). By the TRECK method, a single or repeated shot(s) of diphtheria toxin
      (DT) conditionally ablates a specific cell population from transgenic mice
      expressing the DT receptor transgene under the control of a cell type-specific
      promoter. In some cases of TRECK, frequent and high-dose administration of DT is
      required, raising the concern that these frequent injections of DT could cause
      production of anti-DT antibody, which would neutralize further DT administration.
      To solve this problem, we aimed to generate transgenic mice genetically
      expressing a nontoxic DT mutant, with the expectation that they may naturally
      acquire immune tolerance to DT. Unexpectedly, the G52E DT mutant, which is well
      known as the nontoxic DT variant cross reacting material 197 (CRM197), exhibited
      cytotoxicity in yeast and mammalian cells. Cytotoxicity of CRM197 was abrogated
      in cells mutated for elongation factor 2 (EF-2), indicating that CRM197 exerts
      its toxic effects through EF-2, similar to wild-type DT. On the other hand, the
      K51E/E148K DT mutant exhibited no detectable cytotoxicity. This led us to
      successfully obtain DT gene transgenic mice, which exhibited no histological
      abnormalities, and indeed acquired immune tolerance to DT.

PMID- 17522092
TI  - Merging mouse transcriptome analyses with Parkinson's disease linkage studies.
AB  - The hallmark of Parkinson's disease (PD OMIM #168600) is the degeneration of the
      nigral dopaminergic system affecting approximately 1% of the human population
      older than 65. In pursuit of genetic factors contributing to PD, linkage and
      association studies identified several susceptibility genes. The majority of
      these genes are expressed by the dopamine-producing neurons in the substantia
      nigra. We, therefore, propose expression by these neurons as a selection
      criterion, to narrow down, in a rational manner, the number of candidate genes in
      orphan PD loci, where no mutation has been associated thus far. We determined the
      corresponding human chromosome locations of 1435 murine cDNA fragments obtained
      from murine expression analyses of nigral dopaminergic neurons and combined these
      data with human linkage studies. These fragments represent 19 genes within orphan
      OMIM PD loci. We used the same approach for independent association studies and
      determined the genes in neighborhood to the peaks with the highest LOD score
      value. Our approach did not make any assumptions about disease mechanisms, but
      it, nevertheless, revealed alpha-synuclein, NR4A2 (Nurr1), and the tau genes,
      which had previously been associated to PD. Furthermore, our transcriptome
      analysis identified several classes of candidate genes for PD mutations and may
      also provide insight into the molecular pathways active in nigral dopaminergic
      neurons.

PMID- 17522093
TI  - Intrinsic promoter activities of primary DNA sequences in the human genome.
AB  - In order to understand an overview of promoter activities intrinsic to primary
      DNA sequences in the human genome within a particular cell type, we carried out
      systematic quantitative luciferase assays of DNA fragments corresponding to
      putative promoters for 472 human genes which are expressed in HEK (human
      embryonic kidney epithelial) 293 cells. We observed the promoter activities of
      them were distributed in a bimodal manner; putative promoters belonging to the
      first group (with strong promoter activities) were designated as P1 and the
      latter (with weak promoter activities) as P2. The frequencies of the TATA-boxes,
      the CpG islands, and the overall G + C-contents were significantly different
      between these two populations, indicating there are two separate groups of
      promoters. Interestingly, similar analysis using 251 randomly isolated genomic
      DNA fragments showed that P2-type promoter occasionally occurs within the human
      genome. Furthermore, 35 DNA fragments corresponding to putative promoters of non
      protein-coding transcripts (ncRNAs) shared similar features with the P2 in both
      promoter activities and sequence compositions. At least, a part of ncRNAs, which
      have been massively identified by full-length cDNA projects with no functional
      relevance inferred, may have originated from those sporadic promoter activities
      of primary DNA sequences inherent to the human genome.

PMID- 17522094
TI  - Does cardiovascular risk factor profile influence prescribing of non-steroidal
      anti-inflammatory drugs in a rheumatoid population?

PMID- 17522095
TI  - The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a
      systematic review of randomized clinical trials.
AB  - OBJECTIVE: To systematically review the evidence from randomized clinical trials
      (RCTs) for the effectiveness of the antioxidant vitamins A, C, E or selenium or
      their combination in the treatment of arthritis. METHODSL: A systematic search of
      computerized databases from inception to September 2006 for relevant RCTs,
      application of pre-defined inclusion/exclusion criteria and independent data
      extraction by two authors. Methodological quality was assessed using the Jadad
      scale. RESULTS: The searches identified 20 unique RCTs meeting the inclusion
      criteria: 11 in inflammatory arthritis and 9 in osteoarthritis (OA). The studies
      included are generally of poor quality. They fall into three main clusters:
      selenium for rheumatoid arthritis (n = 5); vitamin E for inflammatory arthritis
      (n = 5) and vitamin E for OA (n = 7). One RCT suggests superiority of vitamin E
      over placebo and three RCTs suggest equivalence between vitamin E and diclofenac
      in the treatment of inflammatory arthritis. In OA, four RCTs compared vitamin E
      with placebo. Two shorter-term studies were positive and two longer-term studies
      were negative. Two further RCTs suggest equivalence between vitamin E and
      diclofenac in the treatment of OA. Findings for selenium, vitamin A and a
      combination product in inflammatory arthritis and for vitamin A, and a
      combination product in OA were negative. An isolated positive result for vitamin
      C in OA is of doubtful clinical significance. CONCLUSIONS: Clinical trials
      testing the efficacy of vitamin E in the treatment of OA and inflammatory
      arthritis have been methodologically weak and have produced contradictory
      findings. There is presently no convincing evidence that selenium, vitamin A,
      vitamin C or the combination product selenium ACE is effective in the treatment
      of any type of arthritis.

PMID- 17522096
TI  - Do baseline characteristics predict response to treatment for low back pain?
      Secondary analysis of the UK BEAM dataset [ISRCTN32683578].
AB  - OBJECTIVES: To identify characteristics of randomized controlled trial
      participants which predict greater benefits from physical treatments for low back
      pain. If successful, this would allow more appropriate selection of patients for
      different treatments. METHODS: We did a secondary analysis of the UK Back pain
      Exercise And Manipulation trial (UK BEAM n = 1334) dataset to identify baseline
      characteristics predicting response to manipulation, exercise and manipulation
      followed by exercise (combined treatment). Rather than simply identifying factors
      associated with overall outcome, we tested for the statistical significance of
      the interaction between treatment allocation, baseline characteristics and
      outcome to identify factors that predicted response to treatment. We also did a
      post-hoc subgroup analysis to present separate results for trial participants
      with subacute and chronic low back pain to inform future evidence synthesis.
      RESULTS: Age, work status, age of leaving school, 'pain and disability', 'quality
      of life' and 'beliefs' at baseline all predicted overall outcome. None of these
      predicted response to treatment. In those allocated to combined treatment, there
      was a suggestion that expecting treatment to be helpful might improve outcome at
      1 yr. Episode length at study entry did not predict response to treatment.
      CONCLUSION: Baseline participant characteristics did not predict response to the
      UK BEAM treatment packages. Using recognized prognostic variables to select
      patients for different treatment packages, without first demonstrating that these
      factors affect response to treatment, may be inappropriate. In particular, this
      analysis suggests that the distinction between subacute and chronic low back pain
      may not be useful when considering treatment choices.

PMID- 17522097
TI  - Recurrent major infections in juvenile-onset systemic lupus erythematosus--a
      close link with long-term disease damage.
AB  - OBJECTIVES: We postulate that patients with systemic lupus erythematosus (SLE)
      having recurrent infections are more likely to have poorer disease outcome. The
      aim of this study is to describe the pattern of infections and disease damage
      that occurred in a cohort of patients with juvenile-onset SLE, and to find out
      whether cumulative disease damage was associated with recurrent infections in
      these patients. METHOD: We retrospectively reviewed (1988-2004) the clinical
      characteristics, infective complications, and disease damage as measured by the
      Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology (SLICC/ACR) Damage Index (SDI) in 47 juvenile-onset SLE patients.
      Potential risk factors for disease damage were evaluated by univariate analysis
      and logistic regression. The correlation between number of major infections and
      disease damage was determined. RESULTS: Thirty-two (68.1%) patients had lupus
      nephropathy and 16 patients (34%) had neuropsychiatric lupus. Sixty-one episodes
      of major infections, defined as infections requiring more than 1 week of
      antimicrobial agents, occurred in 27 patients (57.4%), and 18 patients (31.4%)
      had recurrent major infections (>/= 2 episodes). Organ damage (SDI >/= 1) was
      documented in 21 subjects (44.7%). By logistic regression, occurrence of major
      infections (P < 0.001) was the only significant risk factor for disease damage.
      There was a positive correlation between SDI score with the number of recurrent
      major infections (Spearman's correlation coefficient = 0.50, P < 0.001).
      CONCLUSION: Infections and disease damage are common co-morbidities in juvenile
      onset SLE. Recurrent infections could predict poorer disease outcome and
      associated organ damage in SLE.

PMID- 17522098
TI  - An allograft inflammatory factor 1 (AIF1) single nucleotide polymorphism (SNP) is
      associated with anticentromere antibody positive systemic sclerosis.
AB  - OBJECTIVE: To identify genetic associations between allograft inflammatory factor
      1 (AIF1) and systemic sclerosis (SSc), or its subsets, using a single nucleotide
      polymorphism (SNP) in a replicate case-control study. METHODS: The frequencies of
      alleles and genotypes of an SNP, rs2269475, for the AIF1 gene were examined in
      two large independent cohorts of SSc patients (n = 1015 total), and compared with
      two groups of normal controls (n = 893 total). Both cases and controls were
      stratified by ethnicity (Caucasian, African American and Hispanic) and by
      autoantibody status [anti-centromere antibodies (ACA) and anti-topoisomerase I
      antibody (ATA)]. RESULTS: The minor T allele and CT/TT genotype frequencies of
      the AIF1 SNP were not observed more frequently in SSc patients of the three
      ethnic groups (individually or combined) when compared with controls. On the
      other hand, T and CT/TT frequencies were significantly increased in ACA-positive
      Caucasian SSc patients, and all ACA-positive SSc patients (the three ethnic
      groups combined), when compared with ACA-negative SSc patients and with normal
      controls, with odds ratios of approximately 1.5. CONCLUSION: The data demonstrate
      a genetic association between AIF1 and the ACA-positive subset of SSc. This
      polymorphism is a non-synonymous substitution and therefore likely to represent
      an important functional change in AIF1. Since vascular pathology is a prominent
      feature in ACA-positive SSc patients, the observed association with a
      vasculotrophic inflammatory gene is biologically plausible and warrants further
      research.

PMID- 17522099
TI  - British Society for Rheumatology and British Health Professionals in Rheumatology
      guideline for the management of gout.

PMID- 17522101
TI  - Episodic vertical oscillopsia with progressive gait ataxia: clinical description
      of a new episodic syndrome and evidence of linkage to chromosome 13q.
AB  - We describe four families with late onset episodic vertical oscillopsia and
      progressive gait ataxia. Probands presented between the ages of 40 and 64 years
      with initial symptoms of episodic vertical oscillopsia and interictal downbeat
      nystagmus. A mild gait ataxia developed over several years. Triggers included
      physical exertion, alcohol and caffeine. Patients did not respond to
      acetazolamide. Genetic screening for episodic ataxia types 1 and 2, and
      spinocerebellar ataxias 1, 2, 3 and 6 were negative. Using ancestral identity by
      descent analysis and dense single nucleotide polymorphism (SNP) genotyping
      throughout the genome, an interval of 28.6 cM (approximately 14.2 Mb) on
      chromosome 13q12.11-q13.3, composed of 1259 SNPs, was shared between affected
      individuals in two of the four families and highlighted a region of suggestive
      linkage (LOD >2.7).

PMID- 17522102
TI  - Sporadic Creutzfeldt-Jakob disease in two adolescents.
AB  - BACKGROUND: Sporadic Creutzfeldt-Jakob disease (CJD) is a condition predominantly
      affecting older age groups, with cases aged less than 45 years rare and an age at
      onset or death of less than 20 years exceptional. METHODS: Data from the
      systematic study of sporadic CJD in the UK are available from 1970 onwards.
      Clinical and pathological data are reviewed in order to identify atypical cases,
      including those at the extremes of the age range of sporadic CJD. Detailed
      analysis of atypical cases is undertaken, and in selected cases laboratory
      transmission studies are carried out in order to provide information on the
      characteristics of the infectious agent. RESULTS: In the UK, two cases of
      sporadic CJD in adolescents have been identified, dying at ages 16 and 20 years.
      The first case predated the epidemic of bovine spongiform encephalopathy and the
      characteristics of the second case, including laboratory transmission studies,
      are consistent with a diagnosis of sporadic rather than variant CJD. CONCLUSION:
      The cases in this report indicate that sporadic CJD can develop at a very young
      age, that variant CJD is not the only form of CJD occurring in this age group and
      that neuropathological examination is essential for accurate diagnosis of human
      prion disease.

PMID- 17522103
TI  - Significance of biological markers for predicting prognosis and selecting
      chemotherapy regimens of advanced gastric cancer patients between continuous
      infusion of 5-FU and a combination of 5-FU and cisplatin.
AB  - BACKGROUND: Our previous phase II study of 5-fluorouracil (5-FU) and cisplatin
      (FP) for treatment of advanced gastric cancer showed that strong immunoreactivity
      for vascular endothelial growth factor (VEGF) is associated with chemoresponse.
      Patients with four or five of the favorable phenotypes, p53 (-), bcl-2 (-),
      gluthathione S-transferase pi (-), thymidylate synthase (-), and VEGF (+),
      survived longer than those with three or less of these phenotypes. The purpose of
      this study is to confirm our previous results and to compare the significance of
      those markers between continuous infusion of 5-FU (5-FUci) and FP. METHODS:
      Pretreatment biopsies from 131 of 210 advanced gastric cancer patients enrolled
      to JCOG9205 were analyzed immunohistochemically for the presence of the five
      markers. RESULTS: Median survival times of patients treated with 5-FUci (n = 65)
      or FP (n = 66) were 216 and 253 days, respectively (P = 0.6953). After FP
      treatment, patients with four or five favorable phenotypes (n = 20) survived
      longer than those with three or less favorable phenotypes (n = 46) (334 days and
      243 days, respectively; P = 0.0463), and the survival times of 34 and 32 patients
      with VEGF (-) and (+) were similar (269 days and 253 days, respectively; P =
      0.6317). After 5-FUci, 30 patients with VEGF (+) survived for a shorter time than
      35 patients with VEGF (-) (142 days and 302 days, respectively; P = 0.0043).
      CONCLUSION: The number of favorable phenotypes is prognostic for gastric cancer
      patients treated with FP, and VEGF has a different impact on survival between
      treatment with 5-FUci and FP.

PMID- 17522104
TI  - Diffusion tensor imaging in preclinical and presymptomatic carriers of familial
      Alzheimer's disease mutations.
AB  - Measures are needed that identify persons that will develop Alzheimer's disease
      in order to target them for preventative interventions. There is evidence from
      animal, pathological and imaging studies that disruption of white matter occurs
      in the course of Alzheimer's disease and may be an early event. Prior studies
      have suggested that late-myelinating regions or white matter connecting limbic
      structures are particularly susceptible to degradation. Persons destined to
      develop the disease by virtue of fully penetrant genetic alterations (familial
      Alzheimer's disease or FAD) provide a model in which early and even
      presymptomatic changes of the disease may be identified. In this study we
      performed diffusion tensor imaging (DTI) on 2 demented and 21 subjects at-risk
      for inheriting an FAD mutation. We compared global and localized fractional
      anisotropy (FA) measures in white matter between FAD mutation carriers and non
      carriers in the preclinical (clinical dementia rating <1, n = 20) and
      presymptomatic (clinical dementia rating = 0, n = 15) stages of the disease.
      There were no significant differences between mutation carriers and non-carriers
      with regard to absolute age, age relative to the typical age of disease diagnosis
      in their family, gender or Mini-Mental Status Examination Score. Among
      preclinical FAD mutation carriers (n = 12), mean whole brain white-matter FA (P =
      0.045), FA of the columns of the fornix (P = 0.012), area of the perforant
      pathways bilaterally (right side: P = 0.028, left side: P = 0.027) and left
      orbitofrontal lobe (P = 0.024) were decreased relative to that of non-carriers (n
      = 8). We also found that FA in the columns of the fornix (P = 0.008) and left
      orbitofrontal lobe white matter (P = 0.045) were decreased in the eight
      presymptomatic mutation carriers compared to seven non-carriers. Logistic
      regression demonstrated that FA of the columns of the fornix was a better
      predictor of mutation status than was cross-sectional area of the fornix, global
      mean white-matter FA and left frontal lobe white-matter FA. In a linear
      regression analysis, white-matter volume (P = 0.002), hippocampal volume (P =
      0.023) and mutation status (P = 0.032) significantly predicted fornix FA. We
      conclude that FA is decreased in the white matter in preclinical and even
      presymptomatic FAD mutation carriers, particularly in the late-myelinating tracts
      connecting limbic structures. Decreased FA in of the columns of the fornix is
      particularly robust in early FAD and may provide a biomarker for early disease in
      sporadic Alzheimer's disease.

PMID- 17522105
TI  - Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7
      kilobase deletion in LYK5.
AB  - We used single nucleotide polymorphism (SNP) microarrays to investigate the cause
      of a symptomatic epilepsy syndrome in a group of seven distantly related Old
      Order Mennonite children. Autozygosity mapping was inconclusive, but closer
      inspection of the data followed by formal SNP copy number analyses showed that
      all affected patients had homozygous deletions of a single SNP (rs721575) and
      their parents were hemizygous for this marker. The deleted SNP marked a larger
      deletion encompassing exons 9-13 of LYK5, which encodes STE20-related adaptor
      protein, a pseudokinase necessary for proper localization and function of
      serine/threonine kinase 11 (a.k.a. LKB1). Homozygous LYK5 deletions were
      associated with polyhydramnios, preterm labour and distinctive craniofacial
      features. Affected children had large heads, infantile-onset intractable
      multifocal seizures and severe psychomotor retardation. We designated this
      condition PMSE syndrome (polyhydramnios, megalencephaly and symptomatic
      epilepsy). Thirty-eight percent (N = 16) of affected children died during
      childhood (ages 7 months to 6 years) from medical complications of the disorder,
      which included status epilepticus, congestive heart failure due to atrial septal
      defect and hypernatremic dehydration due to diabetes insipidus. A single post
      mortem neuropathological study revealed megalencephaly, ventriculomegaly,
      cytomegaly and extensive vacuolization and astrocytosis of white matter. There
      was abundant anti-phospho-ribosomal S6 labelling of large cells within the
      frontal cortex, basal ganglia, hippocampus and spinal cord, consistent with
      constitutive activation of the mammalian target of rapamycin (mTOR) signalling
      pathway in brain.

PMID- 17522106
TI  - A student recalls Sir Charles Sherrington, O.M. (1857-1952).

PMID- 17522107
TI  - Probable right atrial thrombus immediately after recombinant activated factor VII
      administration.
AB  - We report the finding of a probable right atrial thrombus in a 33-yr-old male
      patient with severe head, chest, and abdominal trauma. Refractory coagulopathy
      and gross haemodynamic instability ensued, which was only partially controlled
      with massive blood product transfusion and high-dose inotropic support during
      laparotomy. Continuous transoesophageal echocardiography revealed a probable
      atrial thrombus partially occluding the right ventricular inflow tract, which
      appeared immediately after the patient received 100 microg kg(-1) of recombinant
      activated factor VII (rFVIIa) via a left internal jugular central line. This is
      the first report documenting an immediate temporal relationship between rFVIIa
      administration and a space-occupying lesion compatible with localized thrombosis,
      despite ongoing severe systemic coagulopathy. We review the clinical use of
      rFVIIa and discuss possible factors contributing to this event.

PMID- 17522108
TI  - Anti-asthmatic potential of a D-galactose-binding lectin from Synadenium
      carinatum latex.
AB  - Extracts from the plant Synadenium carinatum latex are widely and
      indiscriminately used in popular medicine to treat a great number of inflammatory
      disorders and although the mechanisms underlying these effects remain undefined,
      the lectin isolated from S. carinatum latex (ScLL) is thought to be in part
      responsible for these anti-inflammatory effects. In order to elucidate possible
      immunoregulatory activities of ScLL, we investigated the effects of ScLL
      administration in models of acute and chronic inflammation. Oral administration
      of ScLL significantly inhibited neutrophil and eosinophil extravasation in models
      of acute and chronic inflammation and reduced eosinophil and mononuclear blood
      counts during chronic inflammation. ScLL administration reduced IL(interleukin)-4
      and IL-5 levels but increased interferon-gamma and IL-10 in an asthma
      inflammatory model, which suggested that it might induce a TH2 to TH1 shift in
      the adaptive immune response. ScLL also inhibited IkappaBalpha degradation, a
      negative regulator of proinflammatory NF-kappaB. Taken together, these results
      provide the first description of a single factor isolated from S. carinatum latex
      extract with immunoregulatory functions and suggest that ScLL may be useful in
      the treatment of allergic inflammatory disorders.

PMID- 17522109
TI  - O-linked glycan expression during Drosophila development.
AB  - Mucin-type O-linked glycosylation is an evolutionarily conserved protein
      modification that is essential for viability in Drosophila melanogaster. However,
      the exact role of O-glycans and the identity of the crucial apoproteins modified
      with O-linked N-acetylgalactosamine (O-GalNAc) remain unknown. In an effort to
      elucidate the O-linked glycans expressed during Drosophila development, we have
      employed fluorescent confocal microscopy using a battery of lectins and an
      antibody specific for the GalNAcalpha-Ser/Thr structure (Tn antigen). Confocal
      microscopy provides high-resolution images of the diversity of glycans expressed
      in many developing organ systems. In particular, O-glycans are highly expressed
      on a number of ectodermally derived tissues such as the salivary glands,
      developing gut, and the tracheal system, suggesting a role for O-glycans in cell
      polarity and tube formation common to these organs. Additionally, O-glycans are
      found in the developing nervous system and within subregions of developing
      tissues known to be active in cell signaling events. This study provides us with
      temporal and spatial information regarding O-glycan expression as well as a set
      of reagents for the isolation of glycoproteins from specific developmental stages
      and organ systems. This information will aid us in identifying the in vivo
      substrates of the UDP-GalNAc: polypeptide N-acetylgalactosaminyltranferases, in a
      continuing effort to define the biological role of O-linked glycoproteins during
      development.

PMID- 17522110
TI  - A measure of functional impairment in youth with Tourette's syndrome.
AB  - OBJECTIVE: Tourette's Syndrome (TS) during childhood is linked to varied
      behavioral and psychological difficulties and functional impairment. The current
      study was undertaken to examine both tic-related impairment and impairment from
      other psychological problems in 59 youth (mean age 11.4 years, 69% male) with TS.
      METHODS: Caretakers completed a checklist about the impact of tics and other
      psychological difficulties on family, school, and social functioning. In
      addition, a clinician administered a measure of tic severity to families.
      RESULTS: Over half of the sample reported one significant problem area due to the
      presence of tics, with over a third reporting two or more problem areas. Problems
      were heterogeneous in nature, with no report of a particular problem area in more
      than 25% of the children. The rate of nontic-related impairment was very high,
      with 70% of parents reporting at least one problem area. CONCLUSIONS: Treating
      both tic and nontic-related impairments concurrently may improve functioning more
      so than treating the symptoms separately.

PMID- 17522111
TI  - Identifying barriers to medication adherence in adolescent transplant recipients.
AB  - OBJECTIVE: To create Parent and Adolescent Medication Barriers Scales (PMBS and
      AMBS) for assessing perceived barriers to medication adherence in adolescent
      transplant recipients. METHODS: These scales were developed and initially
      validated with 78 families. Participants responded to questions concerning
      perceived barriers to medication adherence. To assess validity, data on
      contextual factors (e.g., family functioning) and adherence measures were
      collected. RESULTS: A principal components factor analysis resulted in the
      following subscales for the PMBS and AMBS: (a) Disease Frustration/Adolescent
      Issues, (b) Regimen Adaptation/Cognitive Issues, (c) Ingestion Issues, and (d)
      Parent Reminder (PMBS only). Significant associations were found between barrier
      scale scores, contextual factors, and adherence. CONCLUSIONS: The PMBS and AMBS
      are brief and psychometrically promising scales for assessing perceived barriers
      to adherence in adolescent transplant recipients.

PMID- 17522112
TI  - Addressing the issue of falls off playground equipment: an empirically-based
      intervention to reduce fall-risk behaviors on playgrounds.
AB  - OBJECTIVE: The present study evaluated the impact of an intervention to reduce
      fall-risk behaviors on playgrounds among children 6-11 years of age. METHODS:
      Children completed posters indicating risky playground behaviors they would and
      would not do. In the intervention group, video and audio presentations were used
      to expose children to injury occurrences so that injury vulnerability was
      communicated in a fear-evoking way. In the control group, children only completed
      the pre- and post-intervention measures. RESULTS: Significant decreases in
      intentions to risk-take were obtained in the intervention, but not the control
      group. Effectiveness did not vary with children's age or sex, but was greater for
      those scoring high in sensation-seeking. CONCLUSIONS: A fear-appeals approach
      proved successful to reduce intended fall-risk behaviors, particularly for
      children high in sensation-seeking whose risk-taking is motivated by affect
      arousal.

PMID- 17522113
TI  - Motor and perceptual timing deficits among survivors of childhood leukemia.
AB  - OBJECTIVE: There is growing evidence of cerebellar-frontal system change in
      children treated for leukemia with chemotherapy alone (Lesnik et al., 1998).
      METHODS: We compared 22 long-term survivors of acute lymphoblastic leukemia
      (ALL), aged 8-18, to 22 age- and gender-matched controls on tasks emphasizing
      cerebellar-frontal functioning including judgment of time duration and motor
      timing. Groups were also compared on a judgment of pitch task, used as a control
      measure. Children with ALL were at least 5 years from diagnosis, treated with
      intrathecal chemotherapy (methotrexate in all, hydrocortisone and cytarabine in
      20/22), but not radiation therapy, and free from recurrence of disease. RESULTS:
      After controlling for IQ, the ALL group had poorer performance than controls on
      judgment of long duration and motor timing, but not judgment of pitch.
      CONCLUSIONS: Treatment with intrathecal and infusional chemotherapy for childhood
      ALL may be associated with skill deficits comparable to those seen in individuals
      with cerebellar-frontal abnormalities.

PMID- 17522114
TI  - Understanding children's injury-risk behaviors: the independent contributions of
      cognitions and emotions.
AB  - OBJECTIVE: Unintentional injuries are a leading threat to the health of
      elementary-school children, with many injuries happening when children are left
      to make their own decisions about risk taking during play. The present study
      sought to identify determinants of children's physical taking. METHODS: An
      ecologically valid task that posed some threat of injury was used (i.e., highest
      height of a balance beam they would walk across). Ratings of cognitions (extent
      of danger, perceived vulnerability for personal injury, potential severity of
      injury) and emotional reactions (fear, excitement) were taken when on the beam,
      just before the children walked across. RESULTS: Regression analysis, controlling
      for age and sex, revealed that risk taking was predicted from ratings of danger,
      fear, and excitement. CONCLUSIONS: Both cognitive and emotional factors
      independently contribute to predict children's physical risk taking. Theoretical
      and practical implications of these findings are discussed.

PMID- 17522115
TI  - Children of African-American mothers who use crack cocaine: parenting influences
      on youth substance use.
AB  - OBJECTIVE: To examine relationships between parenting behaviors, parent-child
      relationship, and moderating effects of age on youth substance use among a
      community sample of African-American mothers who use crack cocaine and their
      children (12-17 years). METHODS: Maternal-child dyads (n = 208) were recruited
      through street outreach and snowball sampling and completed interviews about
      substance use and parenting. RESULTS: Regression analyses found significant main
      effects of youth age, family conflict, warmth, and disapproval of youth substance
      use on children's substance use. Age x Parenting interactions were significant
      for conflict and disapproval. Higher family conflict increased older youths'
      risk, while higher perceived maternal disapproval protected against substance use
      for older youth. CONCLUSIONS: Family influences may offer risk and protective
      effects for adolescent children of maternal drug users. Outreach and family
      focused interventions that address family conflict and communication of
      disapproval of substance use may help reduce intergenerational risk transmission.
      However, longitudinal research with comprehensive parenting assessments is
      needed.

PMID- 17522116
TI  - Changes in versican and chondroitin sulfate proteoglycans during structural
      development of the lung.
AB  - We have examined whether changes in versican levels, or in the sulfation pattern
      of its chondroitin sulfate (CS) side chains, are associated with the reduction in
      perialveolar tissue volumes that characterize lung maturation in late-gestation
      fetal sheep. Lung tissue was collected from fetuses [90-142 days gestational age
      (GA)] and lambs (2 wk after term birth). The level and distribution of versican
      and CS glycosaminoglycans (GAG) were determined using immunohistochemistry,
      whereas fluorophore-assisted carbohydrate electrophoresis was used to determine
      changes in CS sulfation patterns. Versican was the predominant CS-containing
      proteoglycan in the lung and decreased from 19.9 +/- 2.7 arbitrary units at 90
      days GA to 6.0 +/- 0.5 arbitrary units at 142 days GA, in close association (P <
      0.05) with the reduction in tissue volumes (from 66.0 +/- 4.6 to 25.3 +/- 1.5% at
      142 days); similar reductions occurred for both chondroitin-6-sulfate and
      chondroitin-4-sulfate CS side chains. Hyaluronic acid levels decreased from 3,168
      +/- 641 pmol/microg GAG at 90 days GA to 126 +/- 9 pmol/microg GAG at 142 days
      GA, and the predominant sulfated disaccharide changed from Delta-di-6S at 90 days
      GA to Delta-di-4S at term. These data indicate that structural development of the
      lung is closely associated with marked changes in versican levels and the
      microstructure of CS side chains in perisaccular/alveolar lung tissue.

PMID- 17522117
TI  - Endothelial dysfunction and arterial pressure regulation during early diabetes in
      mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor.
AB  - We determined whether nitric oxide (NO) counters the development of hypertension
      at the onset of diabetes in mice, whether this is dependent on endothelial NO
      synthase (eNOS), and whether non-NO endothelium-dependent vasodilator mechanisms
      are altered in diabetes in mice. Male mice were instrumented for chronic
      measurement of mean arterial pressure (MAP). In wild-type mice, MAP was greater
      after 5 wk of N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 mg x kg(-1) x
      day(-1) in drinking water; 97 +/- 3 mmHg) than after vehicle treatment (88 +/- 3
      mmHg). MAP was also elevated in eNOS null mice (113 +/- 4 mmHg). Seven days after
      streptozotocin treatment (200 mg/kg iv) MAP was further increased in L-NAME
      treated mice (108 +/- 5 mmHg) but not in vehicle-treated mice (88 +/- 3 mmHg) nor
      eNOS null mice (104 +/- 3 mmHg). In wild-type mice, maximal vasorelaxation of
      mesenteric arteries to acetylcholine was not altered by chronic L-NAME or
      induction of diabetes but was reduced by 42 +/- 6% in L-NAME-treated diabetic
      mice. Furthermore, the relative roles of NO and endothelium-derived
      hyperpolarizing factor (EDHF) in acetylcholine-induced vasorelaxation were
      altered; the EDHF component was enhanced by L-NAME and blunted by diabetes. These
      data suggest that NO protects against the development of hypertension during
      early-stage diabetes in mice, even in the absence of eNOS. Furthermore, in
      mesenteric arteries, diabetes is associated with reduced EDHF function, with an
      apparent compensatory increase in NO function. Thus, prior inhibition of NOS
      results in endothelial dysfunction in early diabetes, since the diabetes-induced
      reduction in EDHF function cannot be compensated by increases in NO production.

PMID- 17522118
TI  - Myocardial perfusion during exercise in endurance-trained and untrained humans.
AB  - Because of technical challenges very little is known about absolute myocardial
      perfusion in humans in vivo during physical exercise. In the present study we
      applied positron emission tomography (PET) in order to 1) investigate the effects
      of dynamic bicycle exercise on myocardial perfusion and 2) clarify the possible
      effects of endurance training on myocardial perfusion during exercise. Myocardial
      perfusion was measured in endurance-trained and healthy untrained subjects at
      rest and during absolutely the same (150 W) and relatively similar [70% maximal
      power output (W(max))] bicycle exercise intensities. On average, the absolute
      myocardial perfusion was 3.4-fold higher during 150 W (P < 0.001) and 4.9-fold
      higher during 70% W(max) (P < 0.001) than at rest. At 150 W myocardial perfusion
      was 46% lower in endurance-trained than in untrained subjects (1.67 +/- 0.45 vs.
      3.00 +/- 0.75 ml x g(-1) x min(-1); P < 0.05), whereas during 70% W(max)
      perfusion was not significantly different between groups (P = not significant).
      When myocardial perfusion was normalized with rate-pressure product, the results
      were similar. Thus, according to the present results, myocardial perfusion
      increases in parallel with the increase in working intensity and in myocardial
      work rate. Endurance training seems to affect myocardial blood flow pattern
      during submaximal exercise and leads to more efficient myocardial pump function.

PMID- 17522119
TI  - Visceral pain decreases tolerance to blood loss in conscious female but not male
      rabbits.
AB  - Pain is a component of traumatic blood loss, yet little is known about how pain
      alters the response to blood loss in conscious animals. We evaluated the effects
      of colorectal distension on the cardiorespiratory response to blood loss in six
      male and six female conscious, chronically instrumented New Zealand White
      rabbits. The goal of these experiments was to test the hypotheses that 1)
      colorectal distension would increase tolerance to hemorrhage (i.e., increase the
      blood loss required to decrease mean arterial pressure <or= 40 mmHg); and 2) the
      increase in tolerance would be similar in male and female rabbits. For
      hemorrhage, venous blood was withdrawn until mean arterial pressure decreased to
      <or=40 mmHg. Conscious rabbits underwent three treatments in a balanced design: a
      control hemorrhage, hemorrhage with a colorectal balloon present but not inflated
      (sham CRD), and hemorrhage in the presence of colorectal distension (CRD).
      Colorectal distension reproducibly increased mean arterial pressure, decreased
      respiratory rate, and did not change heart rate. There was no difference in
      control blood loss between males (21.8 +/- 0.3 ml/kg) and females (21.6 +/- 0.3
      ml/kg). However, although CRD blood loss did not change in males (22.8 +/- 0.3
      ml/kg), it was significantly less than control in females (19.1 +/- 0.3 ml/kg; P
      = 0.004). Thus, in conscious rabbits, colorectal distension alters cardiovascular
      control during hemorrhage. Furthermore, colorectal distension did not improve
      tolerance to blood loss in males or females as hypothesized but instead decreased
      tolerance to blood loss only in females.

PMID- 17522120
TI  - Maximal eccentric exercise induces a rapid accumulation of small heat shock
      proteins on myofibrils and a delayed HSP70 response in humans.
AB  - In this study the stress protein response to unaccustomed maximal eccentric
      exercise in humans was investigated. Eleven healthy males performed 300 maximal
      eccentric actions with the quadriceps muscle. Biopsies from vastus lateralis were
      collected at 30 min and 4, 8, 24, 96, and 168 h after exercise. Cellular
      regulation and localization of heat shock protein (HSP) 27, alpha B-crystallin,
      and HSP70 were analyzed by immunohistochemistry, ELISA technique, and Western
      blotting. Additionally, mRNA levels of HSP27, alpha B-crystallin, and HSP70 were
      quantified by Northern blotting. After exercise (30 min), 81 +/- 8% of the
      myofibers showed strong HSP27 staining (P < 0.01) that gradually decreased during
      the following week. alpha B-Crystallin mimicked the changes observed in HSP27.
      After exercise (30 min), the ELISA analysis showed a 49 +/- 13% reduction of the
      HSP27 level in the cytosolic fraction (P < 0.01), whereas Western blotting
      revealed a 15-fold increase of the HSP27 level in the myofibrillar fraction (P <
      0.01). The cytosolic HSP70 level increased to 203 +/- 37% of the control level 24
      h after exercise (P < 0.05). After 4 days, myofibrillar-bound HSP70 had increased
      approximately 10-fold (P < 0.01) and was accompanied by strong staining on cross
      sections. mRNA levels of HSP27, alpha B-crystallin, and HSP70 were all elevated
      the first day after exercise (P < 0.01); HSP70 mRNA showed the largest increase
      (20-fold at 8 h). HSP27 and alpha B-crystallin seemed to respond immediately to
      maximal eccentric exercise by binding to cytoskeletal/myofibrillar proteins,
      probably to function as stabilizers of disrupted myofibrillar structures. Later,
      mRNA and total HSP protein levels, especially HSP70, increased, indicating that
      HSPs play a role in skeletal muscle recovery and remodeling/adaptation processes
      to high-force exercise.

PMID- 17522121
TI  - Effect of cigarette smoke on placental antioxidant enzyme expression.
AB  - Cigarette smoking is associated with systemic oxidative stress leading to an
      upregulation of antioxidant systems [superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx), and heme oxygenase (HO)] in some tissues, but the
      response in the human placenta is unknown. The aim of this study was to determine
      the effect of cigarette smoke exposure on placental antioxidant expression in
      vivo, as well as the effect on antioxidant expression in the human trophoblast
      choriocarcinoma (HTR)-8SVNeo cell line. In the in vivo experiment, normal-term
      placentas were obtained following elective caesarean section. The chorionic villi
      (CV), anchoring villi (AV), and basal plate (BP) were dissected, and Western blot
      analysis was carried out for HO-1, HO-2, SOD, CAT, and GPx. In vitro experiment,
      a cigarette smoke extract (CSE) was prepared by bubbling the smoke form three
      cigarettes through 15 ml of RPMI. This 100% CSE was syringe filtered and diluted
      to 0.1, 0.5, 1, 2, 5, and 10% concentrations. HTR-8SVNeo cells were cultured with
      the CSE for 48 h. The cells were harvested, protein was extracted, and run on SDS
      PAGE gels, and Western blot analysis was carried out for HO-1, HO-2, SOD, and
      CAT. Immunofluorescence for HTR-8SVNeo cells HO-1 was carried out following
      increasing concentrations of CSE. In the in vivo experiment, HO-1 and HO-2
      expression was increased in the BP of placentas from smokers compared with
      nonsmokers. CAT, GPx, and SOD levels in all placental regions, as well as HO-1
      and HO-2 expression in the AV and CV were unchanged. In the in vitro experiment,
      The 5%, 10%, and 20% dilutions were toxic to the cells. The 0.1% CSE solution did
      not significantly alter HO-1 expression. Treatment with the 0.5%, 1% and 2% CSE
      solutions resulted in a dose-dependent increase in HO-1 expression. None of the
      CSE treatments resulted in a significant alteration in HO-2, SOD, GPx, or CAT
      expression. HO-1 immunoflourescence confirmed the HO-1 expression studies.
      Cigarette smoke exposure increases HO-1 and HO-2 expression in the placental
      basal plate and increases HO-1 expression in the HTR-8SVNeo cell line. Increased
      HO-1 and HO-2 protein expression may increase the production of the antioxidants
      biliverdin and bilirubin, which are products of heme metabolism. This could
      function to reduce the oxidative load that is released into the maternal plasma
      from the preeclamptic placenta and may contribute to the observed decreased
      incidence of preeclampsia in smokers.

PMID- 17522122
TI  - Behavioral, metabolic, and molecular stress responses of marine bivalve Mytilus
      galloprovincialis during long-term acclimation at increasing ambient temperature.
AB  - The present study aimed to determine the thermal response of the Mediterranean
      mussel Mytilus galloprovincialis by integrating information from various levels
      of biological organization including behavior, metabolic adjustments, heat shock
      protein expression, and protein kinase activity. Behavioral responses were
      determined by examining the effect of warming on valve closure and opening.
      Metabolic impacts were assessed by examining the activity of the key glycolytic
      enzyme pyruvate kinase (PK). Molecular responses were addressed through the
      expression of Hsp70 and Hsp90 and the phosphorylation of stress-activated protein
      kinases, p38 mitogen-activated protein kinase (p38 MAPK) and cJun-N-terminal
      kinases (JNKs). Mussels increased the duration of valve closure by about sixfold
      when acclimated to 24 degrees C rather than to 17 degrees C. As indicated by the
      activity of PK, such behavior caused metabolic depression and probably a shift
      from aerobic to anaerobic metabolism. Acclimation to temperatures higher than 24
      degrees C caused an increase in mortality and induced the expression of Hsp72.
      Increased phosphorylation of p38 MAPK and JNKs indicated activation of MAPK
      signaling cascades. The potential involvement of MAPKs in the induction of Hsp
      genes in the tissues of M. galloprovincialis is discussed. In conclusion, it
      seems that M. galloprovincialis lives close to its acclimation limits and
      incipient lethal temperature and that a small degree of warming will elicit
      stress responses at whole organism and molecular levels.

PMID- 17522123
TI  - 3,5-Diiodothyronine in vivo maintains euthyroidal expression of type 2
      iodothyronine deiodinase, growth hormone, and thyroid hormone receptor beta1 in
      the killifish.
AB  - Until recently, 3,5-diiodothyronine (3,5-T(2)) has been considered an inactive by
      product of triiodothyronine (T(3)) deiodination. However, studies from several
      laboratories have shown that 3,5-T(2) has specific, nongenomic effects on
      mitochondrial oxidative capacity and respiration rate that are distinct from
      those due to T(3). Nevertheless, little is known about the putative genomic
      effects of 3,5-T(2). We have previously shown that hyperthyroidism induced by
      supraphysiological doses of 3,5-T(2) inhibits hepatic iodothyronine deiodinase
      type 2 (D2) activity and lowers mRNA levels in the killifish in the same manner
      as T(3) and T(4), suggesting a pretranslational effect of 3,5-T(2) (Garcia-G C,
      Jeziorski MC, Valverde-R C, Orozco A. Gen Comp Endocrinol 135: 201-209, 2004).
      The question remains as to whether 3,5-T(2) would have effects under conditions
      similar to those that are physiological for T(3). To this end, intact killifish
      were rendered hypothyroid by administering methimazole. Groups of hypothyroid
      animals simultaneously received 30 nM of either T(3), reverse T(3), or 3,5-T(2).
      Under these conditions, we expected that, if it were bioactive, 3,5-T(2) would
      mimic T(3) and thus reverse the compensatory upregulation of D2 and tyroid
      receptor beta1 and downregulation of growth hormone that characterize
      hypothyroidism. Our results demonstrate that 3,5-T(2) is indeed bioactive,
      reversing both hepatic D2 and growth hormone responses during a hypothyroidal
      state. Furthermore, we observed that 3,5-T(2) and T(3) recruit two distinct
      populations of transcription factors to typical palindromic and DR4 thyroid
      hormone response elements. Taken together, these results add further evidence to
      support the notion that 3,5-T(2) is a bioactive iodothyronine.

PMID- 17522124
TI  - Delayed angiogenesis and VEGF production in CCR2-/- mice during impaired skeletal
      muscle regeneration.
AB  - The regulation of vascular endothelial growth factor (VEGF) levels and angiogenic
      events during skeletal muscle regeneration remains largely unknown. This study
      examined angiogenesis, VEGF levels, and muscle regeneration after cardiotoxin
      (CT)-induced injury in mice lacking the CC chemokine receptor 2 (CCR2). Muscle
      regeneration was significantly decreased in CCR2-/- mice as was the early
      accumulation of macrophages after injury. In both mouse strains, tissue VEGF was
      similar at baseline (no injections) and significantly decreased at day 3 post-CT.
      Tissue VEGF in wild-type (WT) mice was restored within 7 days postinjury but
      remained significantly reduced in CCR2-/- mice until day 21. Capillary density
      (capillaries/mm(2)) within regenerating muscle was maximal in WT mice at day 7
      and double that of baseline muscle. In comparison, maximal capillary density in
      CCR2-/- mice occurred at 21 days postinjury. Maximal capillary density developed
      concurrent with the restoration of tissue VEGF in both strains. A highly
      significant, inverse relationship existed between the size of regenerated muscle
      fibers and capillaries per square millimeter. Although this relationship was
      comparable in WT and CCR2-/- animals, there was a significant decrease in the
      magnitude of this response in the absence of CCR2, reflecting the observation
      that regenerated muscle fiber size in CCR2-/- mice was only 50% of baseline at 42
      days postinjury, whereas WT mice had attained baseline fiber size by day 21. Thus
      CCR2-dependent events in injured skeletal muscle, including impaired macrophage
      recruitment, contribute to restoration of tissue VEGF levels and the dynamic
      processes of capillary formation and muscle regeneration.

PMID- 17522125
TI  - Aging impairs neurogenic contraction in guinea pig urinary bladder: role of
      oxidative stress and melatonin.
AB  - The incidence of urinary bladder disturbances increases with age, and free
      radical accumulation has been proposed as a causal factor. Here we investigated
      the association between changes in bladder neuromuscular function and oxidative
      stress in aging and the possible benefits of melatonin treatment. Neuromuscular
      function was assessed by electrical field stimulation (EFS) of isolated guinea
      pig detrusor strips from adult and aged female guinea pigs. A group of adult and
      aged animals were treated with 2.5 mg x kg(-1) x day(-1) melatonin for 28 days.
      Neurotransmitter blockers were used to dissect pharmacologically the EFS-elicited
      contractile response. EFS induced a neurogenic and frequency-dependent
      contraction that was impaired by aging. This impairment is in part related to a
      decrease in detrusor myogenic contractility. Age also decreased the sensitivity
      of the contraction to pharmacological blockade of purinergic and sensitive fibers
      but increased the effect of blockade of nitrergic and adrenergic nerves. The
      density of cholinergic and nitrergic nerves remained unaltered, but aging
      modified afferent fibers. These changes were associated with an increased level
      of markers for oxidative stress. Melatonin treatment normalized oxidative levels
      and counteracted the aging-associated changes in bladder neuromuscular function.
      In conclusion, these results show that aging modifies neurogenic contraction and
      the functional profile of the urinary bladder plexus and simultaneously increases
      the oxidative damage to the organ. Melatonin reduces oxidative stress and
      improves the age-induced changes in bladder neuromuscular function, which could
      be of importance in reducing the impact of age-related bladder disorders.

PMID- 17522126
TI  - Functional genomics of chicken, mouse, and human titin supports splice diversity
      as an important mechanism for regulating biomechanics of striated muscle.
AB  - Titin is a giant filamentous elastic protein that spans from the Z-disk to M-band
      regions of the sarcomere. The I-band region of titin is extensible and develops
      passive force in stretched sarcomeres. This force has been implicated as a factor
      involved in regulating cardiac contraction. To better understand the adaptation
      in the extensible region of titin, we report the sequence and annotation of the
      chicken and mouse titin genes and compare them to the human titin gene. Our
      results reveal a high degree of conservation within the genomic region encoding
      the A-band segment of titin, consistent with the structural similarity of
      vertebrate A-bands. In contrast, the genomic region encoding the Z-disk and I
      band segments is highly divergent. This is most prominent within the central I
      band segment, where chicken titin has fewer but larger PEVK exons (up to 1,992
      bp). Furthermore, in mouse titin we found two LINE repeats that are inserted in
      the Z-disk and I-band regions, the regions that account for most of the splice
      isoform diversity. Transcript studies show that a group of 55 I-band exons is
      differentially expressed in chicken titin. Consistent with a large degree of
      titin isoform plasticity and variation in PEVK content, chicken skeletal titins
      range in size from approximately 3,000 to approximately 3,700 kDa and vary
      greatly in passive mechanical properties. Low-angle X-ray diffraction experiments
      reveal significant differences in myofilament lattice spacing that correlate with
      titin isoform expression. We conclude that titin splice diversity regulates
      structure and biomechanics of the sarcomere.

PMID- 17522127
TI  - Are pacemaker properties required for respiratory rhythm generation in adult
      turtle brain stems in vitro?
AB  - The role of pacemaker properties in vertebrate respiratory rhythm generation is
      not well understood. To address this question from a comparative perspective,
      brain stems from adult turtles were isolated in vitro, and respiratory motor
      bursts were recorded on hypoglossal (XII) nerve rootlets. The goal was to test
      whether burst frequency could be altered by conditions known to alter respiratory
      pacemaker neuron activity in mammals (e.g., increased bath KCl or blockade of
      specific inward currents). While bathed in artificial cerebrospinal fluid (aCSF),
      respiratory burst frequency was not correlated with changes in bath KCl (0.5-10.0
      mM). Riluzole (50 microM; persistent Na(+) channel blocker) increased burst
      frequency by 31 +/- 5% (P < 0.05) and decreased burst amplitude by 42 +/- 4% (P <
      0.05). In contrast, flufenamic acid (FFA, 20-500 microM; Ca(2+)-activated cation
      channel blocker) reduced and abolished burst frequency in a dose- and time
      dependent manner (P < 0.05). During synaptic inhibition blockade with bicuculline
      (50 microM; GABA(A) channel blocker) and strychnine (50 muM; glycine receptor
      blocker), rhythmic motor activity persisted, and burst frequency was directly
      correlated with extracellular KCl (0.5-10.0 mM; P = 0.005). During synaptic
      inhibition blockade, riluzole (50 microM) did not alter burst frequency, whereas
      FFA (100 microM) abolished burst frequency (P < 0.05). These data are most
      consistent with the hypothesis that turtle respiratory rhythm generation requires
      Ca(2+)-activated cation channels but not pacemaker neurons, which thereby favors
      the group-pacemaker model. During synaptic inhibition blockade, however, the
      rhythm generator appears to be transformed into a pacemaker-driven network that
      requires Ca(2+)-activated cation channels.

PMID- 17522128
TI  - Reversal by relaxin of altered ileal spontaneous contractions in dystrophic (mdx)
      mice through a nitric oxide-mediated mechanism.
AB  - Altered nitric oxide (NO) production/release is involved in gastrointestinal
      motor disorders occurring in dystrophic (mdx) mice. Since the hormone relaxin
      (RLX) can upregulate NO biosynthesis, its effects on spontaneous motility and NO
      synthase (NOS) expression in the ileum of dystrophic (mdx) mice were
      investigated. Mechanical responses of ileal preparations were recorded in vitro
      via force-displacement transducers. Evaluation of the expression of NOS isoforms
      was performed by immunohistochemistry and Western blot. Normal and mdx mice were
      distributed into three groups: untreated, RLX pretreated, and vehicle pretreated.
      Ileal preparations from the untreated animals showed spontaneous muscular
      contractions whose amplitude was significantly higher in mdx than in normal mice.
      Addition of RLX, alone or together with l-arginine, to the bath medium depressed
      the amplitude of the contractions in the mdx mice, thus reestablishing a motility
      pattern typical of the normal mice. The NOS inhibitor N(G)-nitro-L-arginine (L
      NNA) or the guanylate cyclase inhibitor ODQ reversed the effects of RLX. In RLX
      pretreated mdx mice, the amplitude of spontaneous motility was reduced, thus
      resembling that of the normal mice, and NOS II expression in the muscle coat was
      increased in respect to the vehicle-pretreated mdx animals. These results
      indicate that RLX can reverse the altered ileal motility of mdx mice to a normal
      pattern, likely by upregulating NOS II expression and NO biosynthesis in the
      ileal smooth muscle.

PMID- 17522129
TI  - Tachykinin NK3 receptor contribution to systemic release of vasopressin and
      oxytocin in response to osmotic and hypotensive challenge.
AB  - Activation of the neurokinin 3 receptor (NK3R) by a receptor agonist,
      hypotension, and hyperosmolarity results in the internalization of NK3R expressed
      by magnocellular neurons and the release of vasopressin (VP) and oxytocin (OT)
      into the circulation. The contribution of NK3R activation to the release of VP
      and OT in response to hyperosmolarity and hypotension was evaluated by measuring
      the release of both hormones following pretreatment with a selective NK3R
      antagonist, SB-222200. Freely behaving male rats were given an intraventricular
      injection of either 0.15 M NaCl or 250, 500, or 1,000 pmol SB-222200, and then
      were administered an intravenous infusion of 2 M NaCl or 0.15 M NaCl (experiment
      1), or a bolus intra injection of 0.15 M NaCl or hydralazine (HDZ), a hypotension
      inducing drug (experiment 2). Blood samples were taken from indwelling arterial
      catheters at various time points for 1-2 h, both before and after treatments.
      Plasma VP and OT levels were determined by ELISA. Blockade of NK3R did not affect
      the baseline levels of either hormone. In contrast, pretreatment with SB-222200
      significantly reduced ( approximately 60%) or abolished the release of VP and OT,
      respectively, to 2 M NaCl infusion. HDZ-induced VP and OT release was eliminated
      by pretreatment with 500 pmol SB-222200. Therefore, NK3R activation contributes
      significantly to the systemic release of both VP and OT in response to osmotic
      and hypotensive challenges.

PMID- 17522130
TI  - Biological characterization of rodent and human vasopressin V1b receptors using
      SSR-149415, a nonpeptide V1b receptor ligand.
AB  - [(3)H]SSR-149415 is the first tritiated nonpeptide vasopressin V(1b) receptor
      (V(1b)R) antagonist ligand. It was used for studying rodent (mouse, rat, hamster)
      and human V(1b)R from native or recombinant origin. Moreover, a close comparison
      between the human and the mouse V(1b)R was performed using SSR-149415/[(3)H]SSR
      149415 in binding and functional studies in vitro. [(3)H]SSR-149415 binding was
      time-dependent, reversible, and saturable. Scatchard plot analysis gave a single
      class of high-affinity binding sites with apparent equilibrium dissociation
      constant (K(d)) approximately 1 nM and maximum binding density (B(max)) values
      from 7,000 to 300,000 sites/cell according to the cell line. In competition
      experiments, [(3)H]SSR-149415 binding was stereospecific and dose-dependently
      displaced by reference peptide and nonpeptide arginine vasopressin (AVP)/OT
      ligands following a V(1b) rank order of affinity: SSR-149415 = AVP > dCha > dPen
      > dPal > dDavp > SSR-126768A > SR-49059 > SSR-149424 > OT > SR-121463B. Species
      differences between human, rat, mouse, and hamster V(1b)R were observed.
      Autoradiography studies with [(3)H]SSR-149415 on rat and human pituitary showed
      intense specific labeling confined to corticotroph cells and absence of labeling
      in the other tissues examined. SSR-149415 potently and stereospecifically
      antagonized the AVP-induced inositol phosphate production and intracellular
      Ca(2+) increase (EC(50) from 1.83 to 3.05 nM) in recombinant cell lines
      expressing either the mouse or the human V(1b)R. AVP (10(-7) M) exposure of AtT20
      cells expressing mouse or human EGFP-tagged V(1b)R induced their rapid
      internalization. Preincubation with 10(-6) M SSR-149415 counteracted the
      internalization process. Moreover, recycling of internalized receptors was
      observed upon 10(-6) M SSR-149415 treatment. Thus SSR-149415/[(3)H]SSR-149415 are
      unique tools for studying animal and human V(1b)R.

PMID- 17522131
TI  - Work-organisational and personal factors associated with upper body
      musculoskeletal disorders among sewing machine operators.
AB  - OBJECTIVE: To assess the contribution of work-organisational and personal factors
      to the prevalence of work-related musculoskeletal disorders (WMSDs) among garment
      workers in Los Angeles. METHODS: This is a cross-sectional study of self-reported
      musculoskeletal symptoms among 520 sewing machine operators from 13 garment
      industry sewing shops. Detailed information on work-organisational factors,
      personal factors, and musculoskeletal symptoms were obtained in face-to-face
      interviews. The outcome of interest, upper body WMSD, was defined as a worker
      experiencing moderate or severe musculoskeletal pain. Unconditional logistic
      regression models were adopted to assess the association between both work
      organisational factors and personal factors and the prevalence of musculoskeletal
      pain. RESULTS: The prevalence of moderate or severe musculoskeletal pain in the
      neck/shoulder region was 24% and for distal upper extremity it was 16%. Elevated
      prevalence of upper body pain was associated with age less than 30 years, female
      gender, Hispanic ethnicity, being single, having a diagnosis of a MSD or a
      systemic illness, working more than 10 years as a sewing machine operator, using
      a single sewing machine, work in large shops, higher work-rest ratios, high
      physical exertion, high physical isometric loads, high job demand, and low job
      satisfaction. CONCLUSION: Work-organisational and personal factors were
      associated with increased prevalence of moderate or severe upper body
      musculoskeletal pain among garment workers. Owners of sewing companies may be
      able to reduce or prevent WMSDs among employees by adopting rotations between
      different types of workstations thus increasing task variety; by either
      shortening work periods or increasing rest periods to reduce the work-rest ratio;
      and by improving the work-organisation to control psychosocial stressors. The
      findings may guide prevention efforts in the garment sector and have important
      public health implications for this workforce of largely immigrant labourers.

PMID- 17522132
TI  - The role of physical examinations in studies of musculoskeletal disorders of the
      elbow.
AB  - OBJECTIVES: To present data on pain and physical findings from the elbow region,
      and to discuss the role of diagnostic criteria in epidemiological studies of
      epicondylitis. METHODS: From a cohort of computer workers a subgroup of 1369
      participants, who reported at least moderate pain in the neck and upper
      extremities, were invited to a standardised physical examination. Two independent
      physical examinations were performed-one blinded and one not blinded to the
      medical history. Information concerning musculoskeletal symptoms was obtained by
      a baseline questionnaire and a similar questionnaire completed on the day of
      examination. RESULTS: 349 participants met the authors' criteria for being an arm
      case and 249 were elbow cases. Among the 1369 participants the prevalence of at
      least mild palpation tenderness and indirect tenderness at the lateral epicondyle
      was 5.8%. The occurrence of physical findings increased markedly by level of pain
      score. Only about one half with physical findings fulfilled the authors' pain
      criteria for having lateral epicondylitis. A large part with physical findings
      reported no pain at all in the elbow in any of the two questionnaires, 28% and
      22%, respectively. Inter-examiner reliability between blinded and not blinded
      examination was found to be low (kappa value (0.34-0.40)). CONCLUSION: Very few
      with at least moderate pain in the elbow region met common specific criteria for
      lateral epicondylitis. The occurrence of physical findings increased markedly by
      level of pain score and the associations were strongest with pain intensity
      scores given just before the examination. Physical signs were commonly found in
      subjects with no pain complaints. No further impact was achieved if the physical
      examination was not blinded to the medical history. Furthermore, the authors
      propose that pain, clinical signs and disability are studied as separate
      outcomes, and that the diagnoses of lateral epicondylitis should be used only for
      cases with classical signs of inflammation reflected by severe pain, which for
      example conveys some disability.

PMID- 17522133
TI  - Prognostic factors for work ability in sicklisted employees with chronic
      diseases.
AB  - OBJECTIVE: Identifying prognostic factors for work ability in sicklisted
      employees with myocardial infarction (MI), chronic low back pain (cLBP) and major
      depressive disorder (MDD) in order to establish an objective basis for work
      ability evaluation. DESIGN: Systematic literature search in PubMed database (1
      January 1990 to 1 July 2006) with the Yale prognostic research filter. Inclusion
      criteria were as follows: (1) work-disabled employees; (2) MI, cLBP or MDD
      patients; (3) longitudinal designs; and (4) return to work or compensation status
      as outcome measure. RESULTS: four studies on mi met the inclusion criteria and
      described the following prognostic factors for work ability in the acute phase of
      the disease and disablement: lower age; male gender; no financial basis on which
      to retire; lower physical job demands; fewer somatic complaints; no anxiety
      attacks; no diabetes; no heart failure; no atrial fibrillation; no Q waves; and a
      short time interval between MI and presentation at the occupational medicine
      clinic. Two studies on cLBP met the inclusion criteria and described the
      following prognostic factors for work ability after 3 months' work disablement:
      lower age; male gender; no treatment before sick listing; surgery in the first
      year of sick listing; being a breadwinner; less pain; better general health;
      higher job satisfaction; lower physical and/or psychological demands at work; and
      a higher decision latitude at work. No relevant MDD studies were found.
      CONCLUSION: In the earlier phases of work disablement in MI and cLBP patients,
      only a few studies describe disease-specific, environmental and personal
      prognostic factors for return to work. No studies describe prognostic factors for
      MDD. More evidence is needed on the topic of prognostic factors for return to
      work in employees with chronic diseases.

PMID- 17522134
TI  - Interventions to prevent back pain and back injury in nurses: a systematic
      review.
AB  - A systematic literature review was undertaken to assess the effectiveness of
      interventions that aim to prevent back pain and back injury in nurses. Ten
      relevant databases were searched; these were examined and reference lists
      checked. Two reviewers applied selection criteria, assessed methodological
      quality and extracted data from trials. A qualitative synthesis of evidence was
      undertaken and sensitivity analyses performed. Eight randomised controlled trials
      and eight non-randomised controlled trials met eligibility criteria. Overall,
      study quality was poor, with only one trial classified as high quality. There was
      no strong evidence regarding the efficacy of any interventions aiming to prevent
      back pain and injury in nurses. The review identified moderate level evidence
      from multiple trials that manual handling training in isolation is not effective
      and multidimensional interventions are effective in preventing back pain and
      injury in nurses. Single trials provided moderate evidence that stress management
      programs do not prevent back pain and limited evidence that lumbar supports are
      effective in preventing back injury in nurses. There is conflicting evidence
      regarding the efficacy of exercise interventions and the provision of manual
      handling equipment and training. This review highlights the need for high quality
      randomised controlled studies to examine the effectiveness of interventions to
      prevent back pain and injury in nursing populations. Implications for future
      research are discussed.

PMID- 17522135
TI  - External radiation exposure and mortality in a cohort of French nuclear workers.
AB  - OBJECTIVE: To analyse the effect of external radiation exposure on the mortality
      of French nuclear workers. METHODS: A cohort of 29 204 workers employed between
      1950 and 1994 at the French Atomic Energy Commission (Commissariat a l'Energie
      Atomique (CEA)) or at the General Company of Nuclear Fuel (COmpagnie GEnerale des
      MAtieres nucleaires (Cogema, now Areva NC)) was followed up for an average of
      17.8 years. Standardised mortality ratios (SMRs) were computed with reference to
      French mortality rates. Dose-effect relationship were analysed through trend
      tests and Poisson regression, with linear and log-linear models. RESULTS: The
      mean exposure to X and gamma radiation was 8.3 mSv (16.9 mSv for exposed worker
      population). A total of 1842 deaths occurred between 1968 and 1994. A healthy
      worker effect was observed, the number of deaths in the cohort being 59% of the
      number expected from national mortality statistics. Among the 21 main cancer
      sites studied, a statistically significant excess was observed only for skin
      melanoma, and an excess of borderline statistical significance was observed for
      multiple myeloma. A dose-effect relationship was observed for leukaemia after
      exclusion of chronic lymphoid leukaemia (CLL). The relative risk observed for non
      CLL leukaemia, n = 20, was 4.1 per 100 mSv (90% CI 1.4 to 12.2), linear model and
      2.2 per 100 mSv (90% CI 1.2 to 3.3), log-linear model. Significant dose-effect
      relationship were also observed for causes of deaths associated with alcohol
      consumption: mouth and pharynx cancer, cirrhosis and alcoholic psychosis and
      external causes of death. CONCLUSION: The risk of leukaemia increases with
      increasing exposure to external radiation; this is consistent with published
      results on other nuclear workers cohorts.

PMID- 17522136
TI  - Effects of training to implement new working methods to reduce knee strain in
      floor layers. A two-year follow-up.
AB  - OBJECTIVES: Follow-up study after two years to measure the effects of an
      implementation strategy consisting of information, education and training in the
      use of new tools and working-methods for the purpose of reducing knee strain and
      knee complaints in floor layers. METHODS: Training of floor layers (n = 292) in
      using new working methods was evaluated by questionnaires during the courses. Two
      years later, this follow-up included questionnaires for the course participants
      (n = 216) and a control group of floor layers (not trained on courses) (n = 454).
      RESULTS: Two years after training, 38% used the new working methods weekly or
      daily compared to 37% three months after the courses, and 10% before. Among
      controls, only 16% had used the new working methods weekly or daily. The risk of
      knee complaints >30 days (OR 2.46, 95% CI 1.03 to 5.83) or locking of the knees
      (OR 2.89, 95% CI 1.11 to 7.5) was more than double among floor layers who had
      used the new working-methods for less than one year compared to those who had
      used them more. The results were adjusted for age, body mass index, and stress.
      The reduction in more severe knee complaints was greatest if floor layers started
      to use the new working methods before they developed knee problems. Other
      musculoskeletal complaints did not increase. CONCLUSION: This indicates that,
      within a two-year perspective, the implementation strategy to introduce new
      working methods in the floor laying trade has been effective; the number of floor
      layers using the new working-methods has increased, and severe knee problems have
      reduced.

PMID- 17522137
TI  - Field protection effectiveness of chemical protective suits and gloves evaluated
      by biomonitoring.
AB  - OBJECTIVES: To determine the effectiveness of protective suits and gloves by
      biomonitoring. METHODS: Fifteen male spray painters at a ship coating factory
      were studied for two weeks. Workers wore no protective clothing during the first
      week and wore protective suits and gloves during the second week. Sampling was
      conducted on four consecutive working days each week. Ethyl benzene and xylene in
      the air were collected by using 3M 3500 organic vapour monitors. Urine was
      collected before and after each work shift. RESULTS: Urinary mandelic acid (MA)
      and methyl hippuric acid (MHA) levels were divided by the personal exposure
      concentrations of ethyl benzene and xylene, respectively. Mean (SE) corrected MA
      and MHA concentrations in the first week were 1.07 (0.18) and 2.66 (0.68) (mg/g
      creatinine)/(mg/m3), and concentrations in the second week were 0.50 (0.12) and
      1.76 (0.35) (mg/g creatinine)/(mg/m3) in the second week, respectively. Both MA
      and MHA concentrations in the second week (when spray painters wore protective
      suits and gloves) were lower than in the first week, respectively (p<0.001, p =
      0.011). Mean decrease in MA and MHA biomarkers were 69% and 49%, respectively.
      CONCLUSION: This study successfully evaluated the effectiveness of chemical
      protective suits and gloves by using biomarkers as urinary MA and MHA. This
      method is feasible for determining the performance of workers wearing personal
      protective equipment. Moreover, the experimental results suggest that dermal
      exposure may be the major contributor to total body burden of solvents in spray
      painters without protective suits and gloves.

PMID- 17522138
TI  - Mineral dust exposure in young Indian adults: an effect on lung growth?
AB  - BACKGROUND/OBJECTIVE: Long-term occupational exposure to mineral dusts including
      quartz is known to cause pneumoconiosis but little is known about the effects of
      such exposure during the period of lung development in childhood. The objective
      of this study was to investigate the effects on young people of exposure to
      mineral dusts. METHODS: We carried out a cross-sectional study of a group of 81
      Indian stone crushers (average age 21) and a control group of 72 nearby slum
      dwellers (average age 21) in order to assess dust exposures, respiratory symptoms
      and lung function. RESULTS: Stone crushers' corrected 8-hour time weighted
      average concentrations of total inhalable dust, respirable dust and respirable
      crystalline silica were 143 mg/m(3), 39.7 mg/m(3) and 2.29 mg/m(3) respectively,
      which are 14, 10 and 23 times the UK workplace exposure limits, respectively.
      Both groups also had high exposures to outdoor and general domestic particulate
      matter. Compared to controls, stone crushers had significantly more symptoms,
      lower levels of forced vital capacity (FVC) and forced expiratory time (FET) and
      higher levels of forced expiratory volume in one second (FEV(1))/FVC ratio and
      mid-expiratory flow rate (MEF). There were no differences in FEV(1) levels.
      Symptoms and lung function were not associated with time lived on site or time
      spent in job. A selection of chest radiographs showed no silicosis by
      International Labour Office (ILO) criteria. CONCLUSION: Individuals exposed to
      mixed mineral dust in childhood and early adult life had excess symptoms and
      reduced vital capacity without airflow obstruction compared with control
      subjects. We interpret this as evidence of stunting of lung growth caused by
      exposure to respirable dust.

PMID- 17522139
TI  - Work-related injury among direct care occupations in British Columbia, Canada.
AB  - OBJECTIVES: To examine how injury rates and injury types differ across direct
      care occupations in relation to the healthcare settings in British Columbia,
      Canada. METHODS: Data were derived from a standardised operational database in
      three BC health regions. Injury rates were defined as the number of injuries per
      100 full-time equivalent (FTE) positions. Poisson regression, with Generalised
      Estimating Equations, was used to determine injury risks associated with direct
      care occupations (registered nurses [RNs], licensed practical nurses [LPNs) and
      care aides [CAs]) by healthcare setting (acute care, nursing homes and community
      care). RESULTS: CAs had higher injury rates in every setting, with the highest
      rate in nursing homes (37.0 injuries per 100 FTE). LPNs had higher injury rates
      (30.0) within acute care than within nursing homes. Few LPNs worked in community
      care. For RNs, the highest injury rates (21.9) occurred in acute care, but their
      highest (13.0) musculoskeletal injury (MSI) rate occurred in nursing homes. MSIs
      comprised the largest proportion of total injuries in all occupations. In both
      acute care and nursing homes, CAs had twice the MSI risk of RNs. Across all
      settings, puncture injuries were more predominant for RNs (21.3% of their total
      injuries) compared with LPNs (14.4%) and CAs (3.7%). Skin, eye and respiratory
      irritation injuries comprised a larger proportion of total injuries for RNs
      (11.1%) than for LPNs (7.2%) and CAs (5.1%). CONCLUSIONS: Direct care occupations
      have different risks of occupational injuries based on the particular tasks and
      roles they fulfil within each healthcare setting. CAs are the most vulnerable for
      sustaining MSIs since their job mostly entails transferring and repositioning
      tasks during patient/resident/client care. Strategies should focus on prevention
      of MSIs for all occupations as well as target puncture and irritation injuries
      for RNs and LPNs.

PMID- 17522140
TI  - Force suppression and the crossbridge cycle in swine carotid artery.
AB  - Cyclic nucleotides can relax arterial smooth muscle without reductions in
      crossbridge phosphorylation, a process termed force suppression. There are two
      potential mechanisms for force suppression: 1) phosphorylated crossbridges
      binding to thin filaments could be inhibited or 2) the attachment of thin
      filaments to anchoring structures could be disrupted. These mechanisms were
      evaluated by comparing histamine-stimulated swine arterial smooth muscle with and
      without forskolin-induced force suppression and with and without latrunculin-A
      induced actin filament disruption. At matched force, force suppression was
      associated with higher crossbridge phosphorylation and shortening velocity at low
      loads when compared with tissues without force suppression. Shortening velocity
      at high loads, noise temperature, hysteresivity, and stiffness did not differ
      with and without force suppression. These data suggest that crossbridge
      phosphorylation regulates the crossbridge cycle during force suppression. Actin
      disruption with latrunculin-A was associated with higher crossbridge
      phosphorylation when compared with tissues without actin disruption. Shortening
      velocity, noise temperature, hysteresivity, and stiffness did not differ with and
      without actin disruption. These data suggest that actin disruption interferes
      with regulation of crossbridge cycling by crossbridge phosphorylation. Stiffness
      was linearly dependent on stress, suggesting that the force per attached
      crossbridge was not altered with force suppression or actin disruption. These
      data suggest a difference in the mechanical characteristics observed during force
      suppression and actin disruption, implying that force suppression does not
      mechanistically involve actin disruption. These data are most consistent with a
      model where force suppression involves the inhibition of phosphorylated
      crossbridge binding to thin filaments.

PMID- 17522141
TI  - The TTX metabolite 4,9-anhydro-TTX is a highly specific blocker of the Na(v1.6)
      voltage-dependent sodium channel.
AB  - The blocking efficacy of 4,9-anhydro-TTX (4,9-ah-TTX) and TTX on several isoforms
      of voltage-dependent sodium channels, expressed in Xenopus laevis oocytes, was
      tested (Na(v1.2), Na(v1.3), Na(v1.4), Na(v1.5), Na(v1.6), Na(v1.7), and
      Na(v1.8)). Generally, TTX was 40-231 times more effective, when compared with 4,9
      ah-TTX, on a given isoform. An exception was Na(v1.6), where 4,9-ah-TTX in
      nanomole per liter concentrations sufficed to result in substantial block,
      indicating that 4,9-ah-TTX acts specifically at this peculiar isoform. The IC(50)
      values for TTX/4,9-ah-TTX were as follows (in nmol/l): 7.8 +/- 1.3/1,260 +/- 121
      (Na(v1.2)), 2.8 +/- 2.3/341 +/- 36 (Na(v1.3)), 4.5 +/- 1.0/988 +/- 62 (Na(v1.4)),
      1,970 +/- 565/78,500 +/- 11,600 (Na(v1.5)), 3.8 +/- 1.5/7.8 +/- 2.3 (Na(v1.6)),
      5.5 +/- 1.4/1,270 +/- 251 (Na(v1.7)), and 1,330 +/- 459/>30,000 (Na(v1.8)).
      Analysis of approximal half-maximal doses of both compounds revealed minor
      effects on voltage-dependent activation only, whereas steady-state inactivation
      was shifted to more negative potentials by both TTX and 4,9-ah-TTX in the case of
      the Na(v1.6) subunit, but not in the case of other TTX-sensitive ones. TTX
      shifted steady-state inactivation also to more negative potentials in case of the
      TTX-insensitive Na(v1.5) subunit, where it also exerted profound effects on the
      time course of recovery from inactivation. Isoform-specific interaction of toxins
      with ion channels is frequently observed in the case of proteinaceous toxins.
      Although the sensitivity of Na(v1.1) to 4,9-ah-TTX is not known, here we report
      evidence on a highly isoform-specific TTX analog that may well turn out to be an
      invaluable tool in research for the identification of Na(v1.6)-mediated function,
      but also for therapeutic intervention.

PMID- 17522142
TI  - Purinergic agonists stimulate lens Na-K-ATPase-mediated transport via a Src
      tyrosine kinase-dependent pathway.
AB  - The Na-K-ATPase is vital for maintenance of lens transparency. Past studies using
      intact lens suggested the involvement of tyrosine kinases in short-term
      regulation of Na-K-ATPase. Furthermore, in vitro phosphorylation of a lens
      epithelial membrane preparation by Src family kinases (SFKs), a family of
      nonreceptor tyrosine kinases, resulted in modification of Na-K-ATPase activity.
      Here, the effect of purinergic agonists, ATP and UTP, on Na-K-ATPase function and
      SFK activation was examined in the rabbit lens. Na-K-ATPase function was examined
      using two different approaches, measurement of ouabain-sensitive potassium
      ((86)Rb) uptake by the intact lens, and Na-K-ATPase activity in lens epithelial
      homogenates. ATP and UTP caused a significant increase in ouabain-sensitive
      potassium ((86)Rb) uptake. Na-K-ATPase activity was increased in the epithelium
      of lenses pretreated with ATP. Lenses treated with ATP or UTP displayed
      activation of SFKs as evidenced by increased Western blot band density of active
      SFK (phosphorylated at the active loop Y416) and decreased band density of
      inactive SFKs (phosphorylated at the COOH terminal). A single PY416-Src
      immunoreactive band at approximately 60 kDa was observed, suggesting not all Src
      family members are activated. Immunoprecipitation studies showed that band
      density of active Src, and to a lesser extent active Fyn, was significantly
      increased, while active Yes did not change. Preincubation of the lenses with SFK
      inhibitor PP2 abolished the ATP-induced increase in ouabain-sensitive potassium
      ((86)Rb) uptake. The results suggest selective activation of Src and/or Fyn is
      part of a signaling mechanism initiated by purinergic agonists that increases Na
      K-ATPase-mediated transport in the organ-cultured lens.

PMID- 17522143
TI  - Impact of cataract surgery on health-related quality of life in nursing home
      residents.
AB  - AIM: To assess the impact of cataract surgery in nursing home residents on health
      related quality of life, as compared to those who have cataracts but who do not
      undergo surgery. METHODS: A prospective cohort study enrolled 30 nursing home
      residents (>or=60 years old) who had cataracts and underwent cataract surgery,
      and evaluated vision-targeted and generic health-related quality of life and
      depressive symptoms before and approximately 4 months after surgery. This
      cataract surgery group was compared to 15 nursing home residents who had
      cataracts but who did not have surgery, over the same timeframe. RESULTS: Visual
      acuity for near and distance and contrast sensitivity improved following cataract
      surgery (p<0.001). Adjusting for age differences in the two groups, the cataract
      surgery group exhibited significant score improvement in the general vision (p =
      0.005), reading (p = 0.001), psychological distress (p = 0.015), and social
      interaction (p = 0.033) subscales of the Nursing Home Vision-targeted Health
      Related Quality of Life Questionnaire and the VF-14 (p = 0.004). There were no
      group differences in the SF-36, Geriatric Depression Scale or the Cataract
      Symptom Score. CONCLUSION: Nursing home residents who underwent cataract surgery
      because of functional problems experienced significant improvements in their
      vision-targeted health-related quality of life, in addition to dramatically
      improved vision.

PMID- 17522144
TI  - SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high
      frequency of large gene deletions.
AB  - BACKGROUND: Developmental eye anomalies, which include anophthalmia (absent eye)
      or microphthalmia (small eye) are an important cause of severe visual impairment
      in infants and young children. Heterozygous mutations in SOX2, a SOX1B-HMG box
      transcription factor, have been found in up to 10% of individuals with severe
      microphthalmia or anophthalmia and such mutations could also be associated with a
      range of non-ocular abnormalities. METHODS: We performed mutation analysis on a
      new cohort of 120 patients with congenital eye abnormalities, mainly
      anophthalmia, microphthalmia and coloboma. Multiplex ligation-dependent probe
      amplification (MLPA) and fluorescence in situ hybridisation (FISH) were used to
      detect whole gene deletion. RESULTS: We identified four novel intragenic SOX2
      mutations (one single base deletion, one single base duplication and two point
      mutations generating premature translational termination codons) and two further
      cases with the previously reported c.70del20 mutation. Of 52 patients with severe
      microphthalmia or anophthalmia analysed by MLPA, 5 were found to be deleted for
      the whole SOX2 gene and 1 had a partial deletion. In two of these, FISH studies
      identified sub-microscopic deletions involving a minimum of 328 Kb and 550 Kb.
      The SOX2 phenotypes include a patient with anophthalmia, oesophageal
      abnormalities and horseshoe kidney, and a patient with a retinal dystrophy
      implicating SOX2 in retinal development. CONCLUSION: Our results provide further
      evidence that SOX2 haploinsufficiency is a common cause of severe developmental
      ocular malformations and that background genetic variation determines the varying
      phenotypes. Given the high incidence of whole gene deletion we recommend that all
      patients with severe microphthalmia or anophthalmia, including unilateral cases
      be screened by MLPA and FISH for SOX2 deletions.

PMID- 17522145
TI  - Expression of erythropoietin receptor in human epiretinal membrane of
      proliferative diabetic retinopathy.
AB  - PURPOSE: It is widely accepted that intravitreous levels of erythropoietin (Epo)
      are elevated in patients with ischaemic retinal diseases such as proliferative
      diabetic retinopathy (PDR). The aim of this study was to examine the expression
      of Epo and the Epo receptor (EpoR) in epiretinal membranes with and without
      diabetes. METHODS: Eighteen epiretinal membranes (PDR (n = 10), idiopathic
      epiretinal membranes (IERMs) without diabetes (n = 4) and inner limiting
      membranes (ILMs) (n = 4)) were obtained during pars plana vitrectomy. Formalin
      fixed and paraffin-embedded tissues were examined by immunohistochemistry with
      anti-Epo and EpoR antibodies. RESULTS: The histopathological findings
      demonstrated that PDR membranes consisted of a variety of endothelial cells
      forming a microvascular cavity with red blood cells and non-vascular stromal
      mononuclear cells. Membranous and cytoplasmic immunoreactivity for EpoR was
      strongly detected in endothelial cells and stromal cells in all PDR patients.
      Although microvessels were not observed in IERMs and ILMs, immunoreactivity for
      EpoR was noted in the cellular component of IERMs, and was weakly detected in
      ILMs. Epo was not expressed in any membrane. CONCLUSION: EpoR was strongly
      expressed in microvessels of all PDR membranes. The in vivo evidence in this
      study suggests that Epo in the vitreous binds to EpoR in PDR membranes, which
      subsequently leads to the proliferation of new retinal vessels. EpoR
      immunoreactivity in non-vascular stromal cells in PDR membranes, and IERMs and
      ILMs might be indirectly correlated with ischaemia.

PMID- 17522146
TI  - Early onset vitreous amyloidosis in familial amyloidotic polyneuropathy with a
      transthyretin Glu54Gly mutation is associated with elevated vitreous VEGF.
AB  - AIM: To report the early vitreous involvement in a rare familial amyloidotic
      polyneuropathy (FAP) mutation and associated vitreous vascular endothelial growth
      factor (VEGF) levels. DESIGN: Observational case series. METHODS: Review of
      clinical, pathological, photographic, and angiographic records of two FAP
      siblings with severe vitreous involvement. Laboratory ELISA analysis of vitreous
      samples for VEGF, and DNA sequence analysis of peripheral blood for transthyretin
      (TTR) mutational analysis. RESULTS: Two patients underwent 25-gauge vitrectomy in
      three eyes with marked improvement of visual acuity. Neovascularisation seen
      intraoperatively responded to endolaser. Analysis of vitrectomy samples for VEGF
      showed raised levels in all three specimens. Mutational analysis revealed an
      isolated Glu54Gly mutation in the transthyretin gene. CONCLUSIONS: Early
      involvement of the vitreous occurs in a rare transthyretin mutation of FAP, with
      increased vitreous levels of VEGF.

PMID- 17522147
TI  - Persistent diplopia following secondary intraocular lens placement in patients
      with sensory strabismus from uncorrected monocular aphakia.
AB  - AIM: To evaluate the incidence of persistent diplopia after secondary posterior
      chamber intraocular lens (PCIOL) implantation in patients with prolonged
      uncorrected monocular aphakia with associated sensory strabismus. METHODS: A
      retrospective institutional case series (1982 to 2005) of patients with sensory
      strabismus caused by uncorrected monocular aphakia from isolated ocular trauma
      who underwent secondary PCIOL implantation and subsequent successful strabismus
      surgery. RESULTS: Following secondary PCIOL implantation, all 11 identified
      patients complained of new constant binocular diplopia. The mean period of
      uncorrected aphakia was 11 years (range 1 to 20; median and mode, 11). In seven
      patients diplopia could be eliminated before strabismus surgery, using loose
      prisms in free space or a haploscope, or both; these seven patients were diplopia
      free following successful strabismus surgery (and showed suppression on Worth
      four-dot testing). In four patients diplopia could not be eliminated before
      strabismus surgery (either with loose prisms in free space or with a haploscope);
      these four patients had persistent diplopia despite successful strabismus
      surgery. CONCLUSIONS: There is a significant risk of persistent diplopia in this
      setting. Inability to eliminate diplopia before strabismus surgery predicts
      persistent diplopia despite ocular realignment. Sensory testing should be done
      while the patient is still aphakic (with an aphakic contact lens) before
      consideration for secondary PCIOL implantation.

PMID- 17522148
TI  - Inflammatory ocular hypertension syndrome (IOHS) in patients with syphilitic
      uveitis.
AB  - AIM: To determine the prevalence and clinical characteristics of the inflammatory
      ocular hypertension syndrome (IOHS) in patients with uveitis and serological
      evidence of syphilis. METHODS: A retrospective, observational case review of 39
      consecutive patients with uveitis and serological evidence of syphilis was
      carried out between January 1977 and December 2001. Other causes of uveitis were
      excluded. The prevalence and clinical characteristics of IOHS among patients with
      uveitis and serological evidence of syphilis were documented. IOHS was defined as
      an increase in intraocular pressure (IOP) of more than 21 mm Hg that began at the
      onset of acute, recurrent, or chronic anterior chamber inflammation and reversed
      promptly with appropriate anti-inflammatory or antimicrobial treatment. RESULTS:
      Of the 39 patients with uveitis and serological evidence of syphilis, eight eyes
      from seven patients (18%) presented with IOHS, a significantly higher prevalence
      than in the uveitis population at large (2.3%; p<0.001). Best-corrected visual
      acuity varied from 20/20 to 20/200, with a median of 20/40, and three of the
      eight eyes (37.5%) had granulomatous features, including large keratic
      precipitates and, in two eyes, Koeppe nodules. Intraocular pressure varied from
      23 to 51 mm Hg, with a mean of 36 and a median of 34. One patient had bilateral
      IOHS. CONCLUSIONS: Syphilitic uveitis should be included in the differential
      diagnosis of IOHS along with more commonly recognised causes.

PMID- 17522149
TI  - The effect of postmortem time, donor age and sex on the generation of
      neurospheres from adult human retina.
AB  - BACKGROUND/AIM: Postmortem adult human retina contains pluripotent progenitor
      cells capable of forming neurospheres with different retinal cell types. The
      authors examine whether this is the case at all ages and at different postmortem
      times. METHODS: Adult human postmortem retina-derived cell suspensions generated
      neurospheres in fibroblast growth factor 2 and N2 supplement. The yield of
      neurospheres from limited dilution or single cell cultures is very low so the
      authors studied cells generated per 10(5) viable cells from a cell suspension
      derived from whole retina. Retinal tissue from donors aged 18-91 at various
      postmortem times (between 23-44 h) was studied in the context of generation rate
      and time for neurospheres. RESULTS: The potential to generate neurospheres from
      adult human retina remains throughout life. Neurosphere cellular components were
      not affected by donor age or postmortem time (they contained nestin(+), glial
      fibrillary acidic protein(+) and neurofilament(+) cells). An average of 34.36
      neurospheres were generated per 10(5) viable cells. After a few days in culture
      neurospheres begin to form. The time for this to occur was independent of donor
      age but prolonged at longer postmortem times. No significant effect of donor sex
      was found. CONCLUSION: Neurosphere-forming retinal progenitor cells are found in
      adult human retina throughout life. This cell population is a potential target
      for therapeutic intervention to influence repair and regeneration of the retina.

PMID- 17522150
TI  - Protective effects of the sigma agonist Pre-084 in the rat retina.
AB  - AIM: With the rationale that amyloid beta (AB) is toxic to the retina, we here
      assessed the role of TRAIL, a mediator of AB toxicity and related signal
      transduction, in a rat model. We also attempted to demonstrate possible
      protective effects of sigma 1 receptor agonists in these processes. METHODS: AB
      and the sigma 1 receptor agonist Pre-084 were injected intravitreally in the
      anaesthetised rat. In additional experiments, the sigma 1 receptor antagonist
      BD1047 was administered to assess specificity of the effects of Pre-084. Western
      blot analysis was performed on retinas to evaluate the expression of TRAIL and
      TRAIL receptors in the retina, as well as of Bax and phosphorylated JNK following
      the different treatments. Lactic dehydrogenase (LDH) levels were measured as a
      cytotoxicity marker. RESULTS: All TRAIL receptors were expressed in rat retinas.
      Intravitreal injection of AB in rat eyes induced overexpression of TRAIL and the
      proapoptotic protein Bax, as well as phosphorylation of JNK. All these effects of
      AB were abrogated by pretreatment with the sigma(1) receptor agonist Pre-084.
      CONCLUSIONS: It is likely that TRAIL is a mediator of AB effects on the retina.
      In light of their specific inhibitory effects upon TRAIL expression, it is
      plausible to hypothesise that sigma(1) receptor agonists could represent
      potential pharmacological tools for restraining AB related retinal damage.

PMID- 17522151
TI  - Risk of bilateral visual impairment in individuals with amblyopia: the Rotterdam
      study.
AB  - BACKGROUND: The excess risk of bilateral visual impairment (BVI; bilateral visual
      acuity <0.5) among individuals with amblyopia is an argument for screening for
      amblyopia, but data are scarce. METHODS: The risk was estimated by determining
      the incidence of BVI in the Rotterdam Study, a population-based cohort of
      subjects aged 55 years or over (n = 5220), including 192 individuals with
      amblyopia (3.7%). Using a multistate lifetable, the lifetime risk and excess
      period spent with BVI were determined. RESULTS: The relative risk of BVI for
      amblyopes was 2.6 (95% confidence interval 1.4-4.5). For individuals with
      amblyopia, the lifetime risk of BVI was 18%, whereas they lived on average 7.2
      years with BVI. For non-amblyopic individuals, these figures were 10% and 6.7
      years, respectively. CONCLUSION: Amblyopia nearly doubles the lifetime risk of
      BVI and affected individuals spent an extra six months with BVI. This study
      provides data for future cost-effectiveness analyses.

PMID- 17522152
TI  - Incidence of retinal detachment after macular surgery: a retrospective study of
      634 cases.
AB  - AIMS: To evaluate the rate of retinal detachment after macular surgery. METHODS:
      A retrospective non-randomised study of 634 macular surgery procedures was
      undertaken in two academic centres. Idiopathic macular hole (IMH) surgery (n =
      272) and epiretinal membrane (ERM) surgery (n = 362) were performed between 2000
      and 2003. We noted the anatomical and functional results of these procedures and
      we studied serious complications excluding cataract. RESULTS: Minimum follow up
      was 1 year. No retinal detachment (RD) occurred in patients presenting with an
      intraoperative or preoperative successfully treated retinal break (RB). The rate
      of RD occurring after IMH surgery was higher than after the ERM surgical
      procedure (6.6% vs 2.5%, p = 0.02). The rate of RD was higher in patients
      presenting with stage 2 and 3 IMH than with stage 4 IMH. However, lens status as
      well as preoperatively treated RD did not influence the rate of RD after macular
      surgery. CONCLUSION: Retinal detachment remains the most common serious
      complication of macular surgery. Surgical detachment of the posterior vitreous
      face and associated peripheral retina anomaly seem to increase the rate of this
      complication. Careful examination of the peripheral retina is a key issue in
      preventing retinal detachment occurring after macular surgery.

PMID- 17522153
TI  - Individual, group and community risk and protective factors for alcohol and drug
      use among Swedish adolescents.
AB  - BACKGROUND: A number of factors have been identified that protect adolescents or,
      alternatively, put them at risk for drug use and other high-risk behaviours.
      These factors concern different personal and environmental factors, e.g. the
      community, the school setting, family, peer group and individual characteristics.
      The aim of the present study was to examine the associations between risk and
      protective factors and adolescents' use of alcohol and drugs. METHODS: In both
      May 2003 and 2004, random samples of 4800 adolescents (a total of 9600) in Sweden
      were contacted and asked to fill out a questionnaire. It concerned use of alcohol
      and illicit drugs and a large number of adolescent risk and protective factors. A
      total of 5445 (57%) adolescents agreed to participate. RESULTS: About 44% of the
      adolescents in grade 9 (15-16 years of age) had been drunk on at least one
      occasion and nearly 80% of those in grade 11 (17-18 years of age). Almost 15% in
      grade 9 and 40% in grade 11 had been drinking heavily during the previous month,
      and 4% in grade 9 and 12% in grade 11 had used cannabis. Strong associations were
      found between elevated individual, family, school and community risk factors and
      use of alcohol and drugs. Conversely, protective factors were negatively related
      to the use of alcohol and drugs. CONCLUSIONS: This study confirms the importance
      of risk and protective factors within different domains in explaining alcohol and
      drug use among adolescents. The results support efforts targeting multiple risk
      and protective factors in alcohol and drug preventive interventions for
      adolescents.

PMID- 17522154
TI  - 'Children and obesity: a pan-European project examining the role of food
      marketing'.
AB  - BACKGROUND: Rising levels of obesity in school-age children across Europe are
      causing increasing concern. The 'Children, Obesity and associated avoidable
      Chronic Diseases' project sought to examine the effects of promotion within food
      marketing, given the influential role it plays in children's diets. METHOD: A
      questionnaire and data-collection protocol was designed for the national co
      ordinators, facilitating standardized responses. Co-ordinators collected data
      from within 20 European Union countries relating to food promotion to children.
      RESULTS: Results showed that unhealthy foods such as savoury snacks and
      confectionary were the most commonly marketed and consumed by children across all
      countries. Television was found to be the prime promotional medium, with in
      school and internet marketing seen as growth areas. Media literacy programmes
      designed specifically to counterbalance the effects of food marketing to children
      were reported by only a few of the 20 countries. An ineffective and incoherent
      pattern of regulation was observed across the countries as few governments
      imposed tough restrictions with most preferring to persuade industry to
      voluntarily act with responsibly. Most health, consumer and public interest
      groups supported food marketing restrictions whilst industry and media groups
      advocated self-regulation. CONCLUSION: Recommendations include the amendment of
      the European Union's Television Without Frontiers Directive to ban all TV
      advertising of unhealthy food to children, the adoption of a commonly agreed
      European Union definition of an 'unhealthy' food, and the establishment of a
      mechanism for pan-European monitoring of the nature and extent of food marketing
      to children and its regulation.

PMID- 17522155
TI  - Multiple dose-dependent roles for Sox2 in the patterning and differentiation of
      anterior foregut endoderm.
AB  - Sox2 is expressed in developing foregut endoderm, with highest levels in the
      future esophagus and anterior stomach. By contrast, Nkx2.1 (Titf1) is expressed
      ventrally, in the future trachea. In humans, heterozygosity for SOX2 is
      associated with anopthalmia-esophageal-genital syndrome (OMIM 600992), a
      condition including esophageal atresia (EA) and tracheoesophageal fistula (TEF),
      in which the trachea and esophagus fail to separate. Mouse embryos heterozygous
      for the null allele, Sox2(EGFP), appear normal. However, further reductions in
      Sox2, using Sox2(LP) and Sox2(COND) hypomorphic alleles, result in multiple
      abnormalities. Approximately 60% of Sox2(EGFP/COND) embryos have EA with distal
      TEF in which Sox2 is undetectable by immunohistochemistry or western blot. The
      mutant esophagus morphologically resembles the trachea, with ectopic expression
      of Nkx2.1, a columnar, ciliated epithelium, and very few p63(+) basal cells. By
      contrast, the abnormal foregut of Nkx2.1-null embryos expresses elevated Sox2 and
      p63, suggesting reciprocal regulation of Sox2 and Nkx2.1 during early
      dorsal/ventral foregut patterning. Organ culture experiments further suggest that
      FGF signaling from the ventral mesenchyme regulates Sox2 expression in the
      endoderm. In the 40% Sox2(EGFP/COND) embryos in which Sox2 levels are
      approximately 18% of wild type there is no TEF. However, the esophagus is still
      abnormal, with luminal mucus-producing cells, fewer p63(+) cells, and ectopic
      expression of genes normally expressed in glandular stomach and intestine. In all
      hypomorphic embryos the forestomach has an abnormal phenotype, with reduced
      keratinization, ectopic mucus cells and columnar epithelium. These findings
      suggest that Sox2 plays a second role in establishing the boundary between the
      keratinized, squamous esophagus/forestomach and glandular hindstomach.

PMID- 17522156
TI  - Zfrp8, the Drosophila ortholog of PDCD2, functions in lymph gland development and
      controls cell proliferation.
AB  - We have identified a new gene, Zfrp8, as being essential for hematopoiesis in
      Drosophila. Zfrp8 (Zinc finger protein RP-8) is the Drosophila ortholog of the
      PDCD2 (programmed cell death 2) protein of unknown function, and is highly
      conserved in all eukaryotes. Zfrp8 mutants present a developmental delay,
      lethality during larval and pupal stages and hyperplasia of the hematopoietic
      organ, the lymph gland. This overgrowth results from an increase in proliferation
      of undifferentiated hemocytes throughout development and is accompanied by
      abnormal differentiation of hemocytes. Furthermore, the subcellular distribution
      of gamma-Tubulin and Cyclin B is affected. Consistent with this, the phenotype of
      the lymph gland of Zfpr8 heterozygous mutants is dominantly enhanced by the
      l(1)dd4 gene encoding Dgrip91, which is involved in anchoring gamma-Tubulin to
      the centrosome. The overgrowth phenotype is also enhanced by a mutation in Cdc27,
      which encodes a component of the anaphase-promoting complex (APC) that regulates
      the degradation of cyclins. No evidence for an apoptotic function of Zfrp8 was
      found. Based on the phenotype, genetic interactions and subcellular localization
      of Zfrp8, we propose that the protein is involved in the regulation of cell
      proliferation from embryonic stages onward, through the function of the
      centrosome, and regulates the level and localization of cell-cycle components.
      The overproliferation of cells in the lymph gland results in abnormal hemocyte
      differentiation.

PMID- 17522157
TI  - Evolution of the dorsal-ventral patterning network in the mosquito, Anopheles
      gambiae.
AB  - The dorsal-ventral patterning of the Drosophila embryo is controlled by a well
      defined gene regulation network. We wish to understand how changes in this
      network produce evolutionary diversity in insect gastrulation. The present study
      focuses on the dorsal ectoderm in two highly divergent dipterans, the fruitfly
      Drosophila melanogaster and the mosquito Anopheles gambiae. In D. melanogaster,
      the dorsal midline of the dorsal ectoderm forms a single extra-embryonic
      membrane, the amnioserosa. In A. gambiae, an expanded domain forms two distinct
      extra-embryonic tissues, the amnion and serosa. The analysis of approximately 20
      different dorsal-ventral patterning genes suggests that the initial specification
      of the mesoderm and ventral neurogenic ectoderm is highly conserved in flies and
      mosquitoes. By contrast, there are numerous differences in the expression
      profiles of genes active in the dorsal ectoderm. Most notably, the subdivision of
      the extra-embryonic domain into separate amnion and serosa lineages in A. gambiae
      correlates with novel patterns of gene expression for several segmentation
      repressors. Moreover, the expanded amnion and serosa anlage correlates with a
      broader domain of Dpp signaling as compared with the D. melanogaster embryo.
      Evidence is presented that this expanded signaling is due to altered expression
      of the sog gene.

PMID- 17522158
TI  - Transitin, a nestin-like intermediate filament protein, mediates cortical
      localization and the lateral transport of Numb in mitotic avian neuroepithelial
      cells.
AB  - Neuroepithelium is an apicobasally polarized tissue that contains neural stem
      cells and gives rise to neurons and glial cells of the central nervous system.
      The cleavage orientation of neural stem cells is thought to be important for
      asymmetric segregation of fate-determinants, such as Numb. Here, we show that an
      intermediate filament protein, transitin, colocalizes with Numb in the cell
      cortex of mitotic neuroepithelial cells, and that transitin anchors Numb via a
      physical interaction. Detailed immunohistological and time-lapse analyses reveal
      that basal Numb-transitin complexes shift laterally during mitosis, allowing
      asymmetric segregation of Numb-transitin to one of the daughter cells, even when
      the cell cleavage plane is perpendicular to the ventricular surface. In addition,
      RNA interference (RNAi) knockdown of the transitin gene reveals its involvement
      in neurogenesis. These results indicate that transitin has important roles in
      determining the intracellular localization of Numb, which regulates neurogenesis
      in the developing nervous system of avian embryos.

PMID- 17522159
TI  - Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and
      GDNF/WNT11 feedback signalling during kidney branching morphogenesis.
AB  - Antagonists act to restrict and negatively modulate the activity of secreted
      signals during progression of embryogenesis. In mouse embryos lacking the extra
      cellular BMP antagonist gremlin 1 (Grem1), metanephric development is disrupted
      at the stage of initiating ureteric bud outgrowth. Treatment of mutant kidney
      rudiments in culture with recombinant gremlin 1 protein induces additional
      epithelial buds and restores outgrowth and branching. All epithelial buds express
      Wnt11, and Gdnf is significantly upregulated in the surrounding mesenchyme,
      indicating that epithelial-mesenchymal (e-m) feedback signalling is restored. In
      the wild type, Bmp4 is expressed by the mesenchyme enveloping the Wolffian duct
      and ureteric bud and Grem1 is upregulated in the mesenchyme around the nascent
      ureteric bud prior to initiation of its outgrowth. In agreement, BMP activity is
      reduced locally as revealed by lower levels of nuclear pSMAD protein in the
      mesenchyme. By contrast, in Grem1-deficient kidney rudiments, pSMAD proteins are
      detected in many cell nuclei in the metanephric mesenchyme, indicative of
      excessive BMP signal transduction. Indeed, genetic lowering of BMP4 levels in
      Grem1-deficient mouse embryos completely restores ureteric bud outgrowth and
      branching morphogenesis. The reduction of BMP4 levels in Grem1 mutant embryos
      enables normal progression of renal development and restores adult kidney
      morphology and functions. This study establishes that initiation of metanephric
      kidney development requires the reduction of BMP4 activity by the antagonist
      gremlin 1 in the mesenchyme, which in turn enables ureteric bud outgrowth and
      establishment of autoregulatory GDNF/WNT11 feedback signalling.

PMID- 17522160
TI  - The Drosophila homolog of the putative phosphatidylserine receptor functions to
      inhibit apoptosis.
AB  - Exposure of phosphatidylserine is a conserved feature of apoptotic cells and is
      thought to act as a signal for engulfment of the cell corpse. A putative receptor
      for phosphatidylserine (PSR) was previously identified in mammalian systems. This
      receptor is proposed to function in engulfment of apoptotic cells, although gene
      ablation of PSR has resulted in a variety of phenotypes. We examined the role of
      the predicted Drosophila homolog of PSR (dPSR) in apoptotic cell engulfment and
      found no obvious role for dPSR in apoptotic cell engulfment by phagocytes in the
      embryo. In addition, dPSR is localized to the nucleus, inconsistent with a role
      in apoptotic cell recognition. However, we were surprised to find that
      overexpression of dPSR protects from apoptosis, while loss of dPSR enhances
      apoptosis in the developing eye. The increased apoptosis is mediated by the head
      involution defective (Wrinkled) gene product. In addition, our data suggest that
      dPSR acts through the c-Jun-NH(2) terminal kinase pathway to alter the
      sensitivity to cell death.

PMID- 17522161
TI  - Changes in retinoic acid signaling alter otic patterning.
AB  - Retinoic acid (RA) has pleiotropic functions during embryogenesis. In zebrafish,
      increasing or blocking RA signaling results in enlarged or reduced otic vesicles,
      respectively. Here we elucidate the mechanisms that underlie these changes and
      show that they have origins in different tissues. Excess RA leads to ectopic
      foxi1 expression throughout the entire preplacodal domain. Foxi1 provides
      competence to adopt an otic fate. Subsequently, pax8, the expression of which
      depends upon Foxi1 and Fgf, is also expressed throughout the preplacodal domain.
      By contrast, loss of RA signaling does not affect foxi1 expression or otic
      competence, but instead results in delayed onset of fgf3 expression and impaired
      otic induction. fgf8 mutants depleted of RA signaling produce few otic cells, and
      these cells fail to form a vesicle, indicating that Fgf8 is the primary factor
      responsible for otic induction in RA-depleted embryos. Otic induction is rescued
      by fgf8 overexpression in RA-depleted embryos, although otic vesicles never
      achieve a normal size, suggesting that an additional factor is required to
      maintain otic fate. fgf3;tcf2 double mutants form otic vesicles similar to RA
      signaling-depleted embryos, suggesting a signal from rhombomere 5-6 may also be
      required for otic fate maintenance. We show that rhombomere 5 wnt8b expression is
      absent in both RA-signaling-depleted embryos and in fgf3;tcf2 double mutants, and
      inactivation of wnt8b in fgf3 mutants by morpholino injection results in small
      otic vesicles, similar to RA depletion in wild type. Thus, excess RA expands otic
      competence, whereas the loss of RA impairs the expression of fgf3 and wnt8b in
      the hindbrain, compromising the induction and maintenance of otic fate.

PMID- 17522162
TI  - Pneumococcal and influenza vaccines: a survey of knowledge and practice among UK
      paediatricians.

PMID- 17522163
TI  - Ethnic and gender differences in body fat in British schoolchildren as measured
      by DXA.
AB  - BACKGROUND: There are known to be ethnic differences in body composition in
      adults which are related to ethnic differences in adult disease. OBJECTIVES: To
      evaluate gender and ethnic differences in percentage body fat in British
      schoolchildren and to compare these differences with classification of obesity
      using body mass index (BMI) criteria. DESIGN: A cross-sectional study of 1251
      healthy children and adolescents aged 5-18 years from white, South Asian and
      African-Caribbean ethnic groups. Percentage body fat was determined by dual x ray
      absorptiometry and the subjects classified using BMI criteria for overweight and
      obesity. RESULTS: Significant gender differences in percentage body fat were
      seen, with girls having higher values from the age of 5 years. Girls had 3.8%
      higher percentage body fat at 5 years of age increasing to 12.9% at 18 years of
      age. Significant ethnic differences were found, with South Asian girls and boys
      having the highest percentage body fat from 5 and 7 years of age, respectively.
      These differences increased with age, being most significant in the teenage
      years. Although South Asian girls and boys were over-represented in the group
      containing children with more than 25% body fat (p<0.0001, chi2 test), African
      Caribbean subjects were more likely to be classified as obese using BMI criteria.
      CONCLUSIONS: There are clear gender and ethnic differences in percentage body fat
      in British schoolchildren which may relate to known differences in the risk of
      type 2 diabetes in adolescence and adulthood. BMI criteria for defining
      overweight and obesity do not accurately identify ethnic differences in body fat.

PMID- 17522164
TI  - Treatment of fever and over-the-counter medicines.
AB  - Health policy is aimed at increasing homecare and deregulating the supply of
      drugs. This study used parental reports of the treatment of fever as an indicator
      of possible problems that may result from this policy, finding that the use of
      ineffective treatments and the overuse of drugs were common.

PMID- 17522165
TI  - Vitamin K deficiency bleeding: the readiness is all.

PMID- 17522166
TI  - Adaptation of the Manchester-Minneapolis Quality of Life instrument for use in
      the UK population.
AB  - INTRODUCTION: The availability of health-related quality of life (HRQL) measures
      that are reliable, valid, brief and comprehensible and appropriate for use with
      UK children is limited. We report the validation of a HRQL measure suitable for
      UK use in healthy children, children with chronic disease conditions and socially
      disadvantaged children. PATIENTS: A total of 1238 children took part in the
      study, including healthy children as controls (n = 824) and five exemplar groups:
      children diagnosed with asthma (n = 87), diabetes (n = 103) or inflammatory bowel
      disease (IBD; n = 69), children in remission from cancer (n = 68) and children in
      public care (n = 87). METHODS: In phase I, the Manchester-Minneapolis Quality of
      Life instrument (MMQL) Child Form was translated into UK English. In phases II
      and III, the questionnaire was shortened and validated. RESULTS: MMQL was
      anglicised and shortened to five components comprising 29 items. Good internal
      reliability was found with alpha reaching at least 0.69 for all subscales.
      Construct validity was established through moderate correlations with comparable
      PedsQL subscales (Pearson's r ranged from 0.38 to 0.58, p<0.01). Discriminant
      validity was also demonstrated in children with asthma and IBD, children in
      remission from cancer and children in public care, all of whom reported
      significantly lower HRQL than healthy children. Children with diabetes showed
      similar HRQL to their healthy peers. Good reproducibility and moderate
      responsiveness were demonstrated for the new measure. CONCLUSIONS: The anglicised
      and shortened MMQL was shown to be valid and reliable and could be a valuable new
      tool for the assessment of HRQL in children.

PMID- 17522167
TI  - General-purpose filter design for neural prosthetic devices.
AB  - Brain-driven interfaces depend on estimation procedures to convert neural signals
      to inputs for prosthetic devices that can assist individuals with severe motor
      deficits. Previous estimation procedures were developed on an application
      specific basis. Here we report a coherent estimation framework that unifies these
      procedures and motivates new applications of prosthetic devices driven by action
      potentials, local field potentials (LFPs), electrocorticography (ECoG),
      electroencephalography (EEG), electromyography (EMG), or optical methods. The
      brain-driven interface is described as a probabilistic relationship between
      neural activity and components of a prosthetic device that may take on discrete
      or continuous values. A new estimation procedure is developed for action
      potentials, and a corresponding procedure is described for field potentials and
      optical measurements. We test our framework against dominant approaches in an arm
      reaching task using simulated traces of ensemble spiking activity from primary
      motor cortex (MI) and a wheelchair navigation task using simulated traces of EEG
      band power. Adaptive filtering is incorporated to demonstrate performance under
      neuron death and discovery. Finally, we characterize performance under model
      misspecification using physiologically realistic history dependence in MI
      spiking. These simulated results predict that the unified framework outperforms
      previous approaches under various conditions, in the control of position and
      velocity, based on trajectory and endpoint mean squared errors.

PMID- 17522168
TI  - Altered corticostriatal neurotransmission and modulation in dopamine transporter
      knock-down mice.
AB  - Dopamine (DA) modulates glutamate neurotransmission in the striatum. Abnormal DA
      modulation has been implicated in neurological and psychiatric disorders. The
      development of DA transporter knock-down (DAT-KD) mice has permitted modeling of
      these disorders and has shed new light on DA modulation. DAT-KD mice exhibit
      increased extracellular DA, hyperactivity, and alterations in habituation. We
      used whole cell patch-clamp recordings from visually identified striatal neurons
      in slices to examine the effects of DAT-KD on corticostriatal transmission.
      Electrophysiological recordings from medium-sized spiny neurons in the dorsal
      striatum revealed alterations in both amplitude and frequency, of spontaneous
      glutamate receptor-mediated synaptic currents in cells from DAT-KD mice.
      Furthermore, kinetic analyses revealed that these currents had shorter half
      amplitude durations and faster decay times. In contrast, GABA-receptor-mediated
      synaptic currents were not altered. Striatal neurons from DAT-KD mice also
      responded differently to amphetamine, cocaine, and DA D2-receptor agonists or
      antagonists compared with wildtype (WT) littermate controls. In WTs amphetamine
      and cocaine reduced the frequency of spontaneous glutamate currents and these
      effects appeared to be mediated by activation of D2 receptors. In contrast, in
      DAT-KD mice either no changes or only small increases in frequency occurred. D2
      receptor agonists or antagonists also had opposing effects in WT and DAT-KD mice.
      Together, these results indicate that chronically increased extracellular DA
      produces long-lasting changes in corticostriatal communication that may be
      mediated by changes in D2-receptor function. These findings have implications for
      understanding mechanisms underlying attention deficit hyperactivity disorder and
      Tourette's syndrome and may provide insights into novel therapeutic approaches.

PMID- 17522169
TI  - Interspike interval analysis of retinal ganglion cell receptive fields.
AB  - The interspike interval (ISI) preceding a retinal spike has a strong influence on
      whether retinal spikes will drive postsynaptic responses in the lateral
      geniculate nucleus (LGN). This ISI-based filtering of retinal spikes could, in
      principle, be used as a mechanism for processing visual information en route from
      retina to cortex; however, this form of processing has not been previously
      explored. Using a white noise stimulus and reverse correlation analysis, we
      compared the receptive fields associated with retinal spikes over a range of ISIs
      (0-120 ms). Results showed that, although the location and sign of retinal
      ganglion cell receptive fields are invariant to ISI, the size and amplitude of
      receptive fields vary with ISI. These results support the notion that ISI-based
      filtering of retinal spikes can serve as a mechanism for shaping receptive
      fields.

PMID- 17522170
TI  - Rapid and precise retinotopic mapping of the visual cortex obtained by voltage
      sensitive dye imaging in the behaving monkey.
AB  - Retinotopy is a fundamental organizing principle of the visual cortex. Over the
      years, a variety of techniques have been used to examine it. None of these
      techniques, however, provides a way to rapidly characterize retinotopy, at the
      submillimeter range, in alert, behaving subjects. Voltage-sensitive dye imaging
      (VSDI) can be used to monitor neuronal population activity at high spatial and
      temporal resolutions. Here we present a VSDI protocol for rapid and precise
      retinotopic mapping in the behaving monkey. Two monkeys performed a fixation task
      while thin visual stimuli swept periodically at a high speed in one of two
      possible directions through a small region of visual space. Because visual space
      is represented systematically across the cortical surface, each moving stimulus
      produced a traveling wave of activity in the cortex that could be precisely
      measured with VSDI. The time at which the peak of the traveling wave reached each
      location in the cortex linked this location with its retinotopic representation.
      We obtained detailed retinotopic maps from a region of about 1 cm(2) over the
      dorsal portion of areas V1 and V2. Retinotopy obtained during <4 min of imaging
      had a spatial precision of 0.11-0.19 mm, was consistent across experiments, and
      reliably predicted the locations of the response to small localized stimuli. The
      ability to rapidly obtain precise retinotopic maps in behaving monkeys opens the
      door for detailed analysis of the relationship between spatiotemporal dynamics of
      population responses in the visual cortex and perceptually guided behavior.

PMID- 17522171
TI  - Take Your PIC: motoneuronal persistent inward currents may be somatic as well as
      dendritic. focus on "facilitation of somatic calcium channels can evoke prolonged
      tail currents in rat hypoglossal motoneurons".

PMID- 17522172
TI  - Kinematics of the rotational vestibuloocular reflex: role of the cerebellum.
AB  - We studied the effect of cerebellar lesions on the 3-D control of the rotational
      vestibuloocular reflex (RVOR) to abrupt yaw-axis head rotation. Using search
      coils, three-dimensional (3-D) eye movements were recorded from nine patients
      with cerebellar disease and seven normal subjects during brief chair rotations
      (200 degrees /s(2) to 40 degrees /s) and manual head impulses. We determined the
      amount of eye-position dependent torsion during yaw-axis rotation by calculating
      the torsional-horizontal eye-velocity axis for each of three vertical eye
      positions (0 degrees , +/-15 degrees ) and performing a linear regression to
      determine the relationship of the 3-D velocity axis to vertical eye position. The
      slope of this regression is the tilt angle slope. Overall, cerebellar patients
      showed a clear increase in the tilt angle slope for both chair rotations and head
      impulses. For chair rotations, the effect was not seen at the onset of head
      rotation when both patients and normal subjects had nearly head-fixed responses
      (no eye-position-dependent torsion). Over time, however, both groups showed an
      increasing tilt-angle slope but to a much greater degree in cerebellar patients.
      Two important conclusions emerge from these findings: the axis of eye rotation at
      the onset of head rotation is set to a value close to head-fixed (i.e., optimal
      for gaze stabilization during head rotation), independent of the cerebellum and
      once the head rotation is in progress, the cerebellum plays a crucial role in
      keeping the axis of eye rotation about halfway between head-fixed and that
      required for Listing's Law to be obeyed.

PMID- 17522173
TI  - Earth-referenced handrail contact facilitates interlimb cutaneous reflexes during
      locomotion.
AB  - The purpose of this study was to investigate whether the gating of interlimb
      cutaneous reflexes is altered by holding an earth-referenced handrail during
      locomotion. In the first experiment, subjects performed locomotor tasks of
      varying difficulty (level walking, incline walking, and stair climbing) while
      lightly holding an earth-referenced rail. In the second experiment, the extent of
      rail contact and nature of the rail stability (e.g., fixed vs. mobile rail) were
      varied while subjects performed incline walking. Cutaneous reflexes were evoked
      by delivering trains of electrical stimulation to the sural nerve at the ankle.
      EMG data were collected continuously from muscles in the upper and lower limbs
      and trunk. Results showed that modulation of reflexes across the body changed
      when the rail was held. Most interestingly, a facilitatory reflex in the shoulder
      extensor posterior deltoid emerged during swing phase only when subjects held a
      rail. This facilitatory reflex was largest during the more challenging tasks of
      incline walking and stair climbing, A similar reflex facilitation was observed in
      the elbow extensor triceps brachii. The observed facilitation of reflexes in
      triceps brachii and posterior deltoid was specifically expressed only when
      subjects held an earth-referenced rail. This suggests that interlimb reflexes in
      arm extensors may be enhanced to make use of a supportive handrail for stability
      during gait. Therefore, holding a rail may cause global changes in reflex
      thresholds across the body that may have widespread functional relevance for
      assisting in the maintenance of postural stability during locomotion.

PMID- 17522174
TI  - Circuit motifs for spatial orientation behaviors identified by neural network
      optimization.
AB  - Spatial orientation behavior is universal among animals, but its neuronal basis
      is poorly understood. The main objective of the present study was to identify
      candidate patterns of neuronal connectivity (motifs) for two widely recognized
      classes of spatial orientation behaviors: hill climbing, in which the organism
      seeks the highest point in a spatial gradient, and goal seeking, in which the
      organism seeks an intermediate point in the gradient. Focusing on simple networks
      of graded processing neurons characteristic of Caenorhabditis elegans and other
      nematodes, we used an unbiased optimization algorithm to seek values of neuronal
      time constants, resting potentials, and synaptic strengths sufficient for each
      type of behavior. We found many different hill-climbing and goal-seeking networks
      that performed equally well in the two tasks. Surprisingly, however, each hill
      climbing network represented one of just three fundamental circuit motifs, and
      each goal-seeking network comprised two of these motifs acting in concert. These
      motifs are likely to inform the search for the real circuits that underlie these
      behaviors in nematodes and other organisms.

PMID- 17522175
TI  - Facilitation of somatic calcium channels can evoke prolonged tail currents in rat
      hypoglossal motoneurons.
AB  - Voltage-dependent persistent inward currents (PICs) make an important
      contribution to the input-output properties of alpha motoneurons. PICs are
      thought to be mediated by membrane channels located primarily on the dendrites as
      evidenced by prolonged tail currents following the termination of a voltage step
      and by a clockwise hysteresis in the whole cell inward currents recorded in
      response to depolarizing then repolarizing voltage ramp commands. We report here,
      however, that voltage-clamp currents with these same features can be generated in
      isolated somatic membrane patches from rat hypoglossal motoneurons. Long-lasting
      (200-800 ms) tail currents after 1-s voltage-clamp pulses were observed in
      nucleated patches from 16 of 23 cells. Further, these somatic PICs display
      "facilitation" in response to conditioning depolarization as previously observed
      in whole cell recordings from intact neurons. Pharmacological tests suggest that
      the PICs were primarily mediated by Cav1 channels. Our results show that many of
      the features of persistent calcium currents recorded from intact motoneurons do
      not necessarily reflect a remote dendritic origin but can also be ascribed to the
      intrinsic properties of their Cav1 channels.

PMID- 17522176
TI  - Influence of viscous loads on motor planning.
AB  - Here we computationally investigate how encumbering the hand could alter
      predictions made by the minimum torque change (MTC) and minimum endpoint variance
      hypotheses (MEPV) of movement planning. After minutes of training, people have
      made arm trajectories in a robot-generated viscous force field that were similar
      to previous baseline trajectories without the force field. We simulate the human
      arm interacting with this viscous load. We found that the viscous forces clearly
      differentiated MTC and MEPV predictions from both minimum-jerk predictions and
      from human behavior. We conclude that learned behavior in the viscous environment
      could arise from minimizing kinematic costs but could not arise from a
      minimization of either torque change or endpoint variance.

PMID- 17522177
TI  - EEG sharp waves and sparse ensemble unit activity in the macaque hippocampus.
AB  - Neural unit activity and EEGs were recorded from inferior temporal regions of
      three rhesus macaques chronically implanted with "hyperdrives" holding 12
      individually movable tetrodes. Recordings were made from each monkey over a
      period of approximately 3 mo, while the electrodes were moved by small increments
      through the hippocampus and neighboring structures. After recording, the monkeys
      were necropsied, and the brains were sectioned and Nissl-stained, permitting
      identification of individual electrode tracks. The results establish that
      hippocampal pyramidal cells are "complex spike cells," firing at overall average
      rates of approximately 0.3 Hz, with spike trains consisting of long periods of
      silence interspersed with bursts of activity. The results also establish that the
      monkey hippocampal EEG shows "sharp wave" events consisting of a high-frequency
      "ripple" oscillation ( approximately 110 Hz) together with a large slow-wave EEG
      deflection lasting several hundred milliseconds. The evidence suggests that
      monkey sharp waves are probably generated mainly in the CA1 region and that sharp
      waves are associated with an inactive/drowsy-or-sleeping behavioral state, which
      is also associated with increased hippocampal pyramidal cell activity and
      increased hippocampal EEG amplitude. The results of this initial study of
      ensembles of primate hippocampal neurons are consistent with previous studies in
      rodents and consistent with the hypothesis that theories and models of
      hippocampal memory function developed on the basis of rat data may be applicable
      to a wide range of mammalian species.

PMID- 17522178
TI  - Sodium currents in mesencephalic trigeminal neurons from Nav1.6 null mice.
AB  - Previous studies using pharmacological methods suggest that subthreshold sodium
      currents are critical for rhythmical burst generation in mesencephalic trigeminal
      neurons (Mes V). In this study, we characterized transient (I(NaT)), persistent
      (I(N)(aP)), and resurgent (I(res)) sodium currents in Na(v)1.6-null mice (med
      mouse, Na(v)1.6(-/-)) lacking expression of the sodium channel gene Scn8a. We
      found that peak transient, persistent, and resurgent sodium currents from med
      (Na(v)1.6(-/-)) mice were reduced by 18, 39, and 76% relative to their wild-type
      (Na(v)1.6(+/+)) littermates, respectively. Current clamp recordings indicated
      that, in response to sinusoidal constant amplitude current (ZAP function), all
      neurons exhibited membrane resonance. However, Mes V neurons from med mice had
      reduced peak amplitudes in the impedance-frequency relationship (resonant Q
      value) and attenuated subthreshold oscillations despite the similar passive
      membrane properties compared with wild-type littermates. The spike frequency
      current relationship exhibited reduced instantaneous discharge frequencies and
      spike block at low stimulus currents and seldom showed maintained spike discharge
      throughout the stimulus in the majority of med neurons compared with wild-type
      neurons. Importantly, med neurons never exhibited maintained stimulus-induced
      rhythmical burst discharge unlike those of wild-type littermates. The data showed
      that subthreshold sodium currents are critical determinants of Mes V
      electrogenesis and burst generation and suggest a role for resurgent sodium
      currents in control of spike discharge.

PMID- 17522179
TI  - Spinal and supraspinal effects of long-term stimulation of sensorimotor cortex in
      rats.
AB  - Sensorimotor cortex (SMC) modifies spinal cord reflex function throughout life
      and is essential for operant conditioning of the H-reflex. To further explore
      this long-term SMC influence over spinal cord function and its possible clinical
      uses, we assessed the effect of long-term SMC stimulation on the soleus H-reflex.
      In freely moving rats, the soleus H-reflex was measured 24 h/day for 12 wk. The
      soleus background EMG and M response associated with H-reflex elicitation were
      kept stable throughout. SMC stimulation was delivered in a 20-day-on/20-day
      off/20-day-on protocol in which a train of biphasic 1-ms pulses at 25 Hz for 1 s
      was delivered every 10 s for the on-days. The SMC stimulus was automatically
      adjusted to maintain a constant descending volley. H-reflex size gradually
      increased during the 20 on-days, stayed high during the 20 off-days, and rose
      further during the next 20 on-days. In addition, the SMC stimulus needed to
      maintain a stable descending volley rose steadily over days. It fell during the
      20 off-days and rose again when stimulation resumed. These results suggest that
      SMC stimulation, like H-reflex operant conditioning, induces activity-dependent
      plasticity in both the brain and the spinal cord and that the plasticity
      responsible for the H-reflex increase persists longer after the end of SMC
      stimulation than that underlying the change in the SMC response to stimulation.

PMID- 17522180
TI  - A biocompatible titanium headpost for stabilizing behaving monkeys.
AB  - Many neurophysiological experiments involving monkeys require that the head be
      stabilized while the animal performs a task. Often a post is attached to the
      skull to accomplish this goal, using a headcap formed from dental acrylic. We
      describe a new headpost, developed by refinement of several prototypes, and
      supply an AutoCAD file to aid in machine shop production. This headpost is
      fabricated from a single piece of commercially pure titanium. It has a footplate
      consisting of four limbs arranged in the configuration of a "K." These are bent
      during surgery to match the curvature of the skull and attached with specialized
      titanium bone screws. Headposts were implanted in seven rhesus monkeys ranging in
      age from 2 yr to adult. None has been rejected after up to 17 mo of regular use.
      They require little or no daily toilette and create only a 0.80-cm(2) defect in
      the scalp. Computed tomography after implantation showed that the skull undergoes
      remodeling to embed the footplate in bone. This finding was confirmed by necropsy
      in two subjects. The outer table of the skull had grown over the titanium
      footplate, whereas the inner table had thickened to bury the tips of the titanium
      screws. The remarkable strength of the skull/implant bond was demonstrated by
      applying increasing amounts of torque to the headpost. At 26.3 Nm, the headpost
      tore from its metal footplate, but no screws came loose. The excellent
      performance of this implant is explained by integration of biocompatible titanium
      into remodeled bone tissue. The headpost is simpler to implant, more securely
      anchored, easier to maintain, and less obtrusive than devices attached with
      acrylic.

PMID- 17522181
TI  - Critical role for sphingosine kinase-1 in regulating survival of neuroblastoma
      cells exposed to amyloid-beta peptide.
AB  - We examined the role of sphingosine kinase-1 (SphK1), a critical regulator of the
      ceramide/sphingosine 1-phosphate (S1P) biostat, in the regulation of death and
      survival of SH-SY5Y neuroblastoma cells in response to amyloid beta (Abeta)
      peptide (25-35). Upon incubation with Abeta, SH-SY5Y cells displayed a marked
      down-regulation of SphK1 activity coupled with an increase in the ceramide/S1P
      ratio followed by cell death. This mechanism was redox-sensitive; N
      acetylcysteine totally abrogated the down-regulation of SphK1 activity and
      strongly inhibited Abeta-induced cell death. SphK1 overexpression impaired the
      cytotoxicity of Abeta, whereas SphK1 silencing by RNA interference mimicked Abeta
      induced cell death, thereby establishing a critical role for SphK1. We further
      demonstrated that SphK1 could mediate the well established cytoprotective action
      of insulin-like growth factor (IGF-I) against Abeta toxicity. A dominant-negative
      form of SphK1 or its pharmacological inhibition not only abrogated IGF-I
      triggered stimulation of SphK1 but also hampered IGF-I protective effect.
      Similarly to IGF-I, the neuroprotective action of TGF-beta1 was also dependent on
      SphK1 activity; activation of SphK1 as well as cell survival were impeded by a
      dominant-negative form of SphK1. Taken together, these results provide the first
      illustration of SphK1 role as a critical regulator of death and survival of Abeta
      treated cells.

PMID- 17522182
TI  - Brain-derived neurotrophic factor: linking fear learning to memory consolidation.
AB  - Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family,
      plays an important role in synaptic plasticity. In this issue of Molecular
      Pharmacology, Ou and Gean (p. 350) thoroughly describe the molecular cascade by
      which fear learning leads to an increase in BDNF expression in the lateral
      amygdala (LA). Calcium influx through N-methyl-D-aspartate receptors and L-type
      voltage-dependent calcium channels, which occurs in the LA during fear
      conditioning, activates protein kinase A and Ca2+/calmodulin-dependent protein
      kinase IV. Each induces phosphorylation of cAMP response element-binding protein,
      which binds to the BDNF promoter, leading to BDNF expression in the LA, and
      contributes to fear memory consolidation.

PMID- 17522183
TI  - Challenges and opportunities of trapping ligands.
AB  - Because gonadotropin-releasing hormone (GnRH) analogs constitute an important
      class of therapeutics for various reproductive and hormone-dependent disorders,
      many novel compounds have been discovered and studied. Several orally active
      nonpeptide GnRH antagonists have recently gained increased attention. In the
      study published in this issue of Molecular Pharmacology, Kohout et al. (p. 238)
      used small-molecule TAK-013 (sufugolix; developed previously by Takeda Chemical
      Industries) as a tool to elucidate the mechanism of its insurmountable
      antagonism. On the basis of receptor mutagenesis combined with molecular
      modeling, the authors hypothesized that certain amino acid sequences uniquely
      present in the human GnRH receptor amino terminus and extracellular loop 2 may
      form a "trap door" retarding dissociation of TAK-013. Such a trapping mechanism
      could be both ligand- and receptor species-specific. Although analogous models
      were previously proposed for other G protein-coupled receptors, the study by
      Kohout et al. (2007) provides an important advance in the GnRH antagonists field
      and an illustration of the fact that preclinical studies using animal models with
      nonhuman receptors may have very limited value in predicting drug efficacy in
      human disease. There are many examples showing that high-affinity protein,
      peptide, or nonpeptide agonists or antagonists have also enhanced clinical
      efficacy. However, there are also numerous studies indicating that very high
      receptor binding affinity is not a guarantee of drug efficacy and that other
      factors, including pharmacokinetic profile, ligand-induced receptor
      desensitization, and "trafficking," are critical in design and development of
      optimal drugs.

PMID- 17522184
TI  - Critical care nurses as coworkers: are our interactions nice or nasty?

PMID- 17522185
TI  - Chocolate and our heart.

PMID- 17522186
TI  - My experience of being present during resuscitation.

PMID- 17522187
TI  - Financial effect of rapid response teams.

PMID- 17522188
TI  - Sympathetic storming in acute conditions.

PMID- 17522189
TI  - Portrayal of telemetry nurses.

PMID- 17522190
TI  - Fostering synergy: a nurse-managed remote telemetry model.

PMID- 17522191
TI  - Meeting the needs of graduate nurses in critical care orientation: staged
      orientation program in surgical intensive care.

PMID- 17522192
TI  - Bronchiolitis obliterans organizing pneumonia.

PMID- 17522193
TI  - Critical care nurses' work environments: value of excellence in Beacon units and
      Magnet organizations.

PMID- 17522194
TI  - Is it an expected practice for critical care nurses to irrigate an external
      ventriculostomy drainage (EVD) system with tissue plasminogen activator (tPA) to
      break up blood clots in the tubing to facilitate drainage, thereby preventing
      increased intracranial pressure?

PMID- 17522195
TI  - Electrocardiography course revisions. Improve students' test scores.

PMID- 17522196
TI  - A functional heat shock protein 90 chaperone is essential for efficient flock
      house virus RNA polymerase synthesis in Drosophila cells.
AB  - The molecular chaperone heat shock protein 90 (Hsp90) is involved in multiple
      cellular processes including protein maturation, complex assembly and
      disassembly, and intracellular transport. We have recently shown that a
      disruption of Hsp90 activity in cultured Drosophila melanogaster cells suppresses
      Flock House virus (FHV) replication and the accumulation of protein A, the FHV
      RNA-dependent RNA polymerase. In the present study, we investigated whether the
      defect in FHV RNA polymerase accumulation induced by Hsp90 suppression was
      secondary to an effect on protein A synthesis, degradation, or intracellular
      membrane association. Treatment with the Hsp90-specific inhibitor geldanamycin
      selectively reduced FHV RNA polymerase synthesis by 80% in Drosophila S2 cells
      stably transfected with an inducible protein A expression plasmid. The
      suppressive effect of geldanamycin on protein A synthesis was not attenuated by
      proteasome inhibition, nor was it sensitive to changes in either the mRNA
      untranslated regions or protein A intracellular membrane localization.
      Furthermore, geldanamycin did not promote premature protein A degradation, nor
      did it alter the extremely rapid kinetics of protein A membrane association.
      These results identify a novel role for Hsp90 in facilitating viral RNA
      polymerase synthesis in Drosophila cells and suggest that FHV subverts normal
      cellular pathways to assemble functional replication complexes.

PMID- 17522197
TI  - Memory CD4+ T-lymphocyte loss and dysfunction during primary simian
      immunodeficiency virus infection.
AB  - It has long been appreciated that CD4+ T lymphocytes are dysfunctional in human
      immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV)-infected
      individuals, and it has recently been shown that HIV/SIV infections are
      associated with a dramatic early destruction of memory CD4+ T lymphocytes.
      However, the relative contributions of CD4+ T-lymphocyte dysfunction and loss to
      immune dysregulation during primary HIV/SIV infection have not been fully
      elucidated. In the current study, we evaluated CD4+ T lymphocytes and their
      functional repertoire during primary SIVmac251 infection in rhesus monkeys. We
      show that the extent of loss of memory CD4+ T lymphocytes and staphylococcal
      enterotoxin B-stimulated cytokine production by total CD4+ T lymphocytes during
      primary SIVmac251 infection is tightly linked in a cohort of six rhesus monkeys
      to set point plasma viral RNA levels, with greater loss and dysfunction being
      associated with higher steady-state viral replication. Moreover, in exploring the
      mechanism underlying this phenomenon, we demonstrate that the loss of functional
      CD4+ T lymphocytes during primary SIVmac251 infection is associated with both a
      selective depletion of memory CD4+ T cells and a loss of the functional capacity
      of the memory CD4+ T lymphocytes that escape viral destruction.

PMID- 17522198
TI  - Rates of reactivation of latent herpes simplex virus from mouse trigeminal
      ganglia ex vivo correlate directly with viral load and inversely with number of
      infiltrating CD8+ T cells.
AB  - Herpes simplex viruses (HSV) reactivate at rates proportional to the viral loads
      in latently infected ganglia. However, these rates vary substantially among
      infected animals. We assessed whether the numbers of HSV-specific CD8(+) T cells
      infiltrating latently infected ganglia also affect reactivation rates and
      contribute to their variability. Following corneal infection of mice with HSV
      type 2 (HSV-2), we quantified the latent viral loads in dissociated trigeminal
      ganglia by real-time PCR, the numbers of infiltrating CD8(+) T cells by flow
      cytometry, and the rates of reactivation by the detection of cell-free virus
      released from ganglion cells cultured in 96-well plates. The reactivation rates
      correlated directly with the latent viral loads (P = 0.001) but did so more
      strongly (P = 10(-7)) when cultures were depleted of CD8(+) T cells. Reactivation
      rates were reduced in a dose-dependent fashion by adding back ganglion CD8(+) T
      cells to the cultures (P = 0.003). We related the latent viral loads, numbers of
      CD8(+) T cells, and reactivation rates by mathematical equations. The rates of
      reactivation predicted from latent viral loads and numbers of infiltrating CD8(+)
      T cells in dissociated ganglia correlated with the observed rates of reactivation
      (P = 0.04). The reactivation of HSV-2 from ganglia ex vivo is determined both by
      the latent viral load and the number of infiltrating CD8(+) T cells.

PMID- 17522199
TI  - A herpes simplex virus gD-YFP fusion glycoprotein is transported separately from
      viral capsids in neuronal axons.
AB  - Two models describing how alphaherpesviruses exit neurons differ with respect to
      whether nucleocapsids and envelope glycoproteins travel toward axon termini
      separately or as assembled enveloped virions. Recently, a pseudorabies virus
      glycoprotein D (gD)-green fluorescent protein fusion was found to colocalize with
      viral capsids, supporting anterograde transport of enveloped virions. Previous
      antibody staining experiments demonstrated that herpes simplex virus (HSV)
      glycoproteins and capsids are separately transported in axons. Here, we generated
      an HSV expressing a gD-yellow fluorescent protein (YFP) fusion and found that gD
      YFP and capsids were transported separately in neuronal axons. Anti-gD antibodies
      colocalized with gD-YFP, indicating that gD-YFP behaves like wild-type HSV gD.

PMID- 17522200
TI  - Differential requirements of NS4A for internal NS3 cleavage and polyprotein
      processing of hepatitis C virus.
AB  - The NS3 protein of hepatitis C virus (HCV) possesses protease activity
      responsible for the proteolytic cleavage of the viral polyprotein at the
      junctions of nonstructural proteins downstream of NS3. The NS3 protein was also
      found to be internally cleaved. In this study, we demonstrated that internal
      cleavages occurred on the NS3 protein of genotype 1b in the presence of NS4A,
      both in culture cells and with a mouse model system. No internal cleavage
      products were detected with the NS3 and NS4A proteins of genotype 2a. Three
      potential cleavage sites were detected in the NS3 protein (genotype 1b), with
      IPT(402)|S being the major one. The internal cleavage requires the polyprotein
      processing activity of NS3 protease, but when supplemented in trans, the internal
      cleavage efficiency is reduced. In addition, several mutations in NS4A disrupted
      the internal cleavage of NS3 but did not affect polyprotein processing,
      indicating that NS4A contributes differently to these two proteolytic activities.
      Furthermore, Ile-25, Val-26, and Ile-29 of the NS4A protein, important for the
      NS4A-dependent internal cleavages, were also shown to be critical for the
      transforming activity of NS3, but mutations at these critical residues resulted
      only in a slight increase of HCV replicating efficiency. The internal cleavage
      associated enhancement of the transforming activity of NS3 was reduced when a
      T402A substitution at the major internal cleavage site was introduced. The
      multiple roles of NS4A in viral multiplication and pathogenesis make NS4A an
      ideal molecular target for HCV therapy.

PMID- 17522201
TI  - CCR5Delta32 protein expression and stability are critical for resistance to human
      immunodeficiency virus type 1 in vivo.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of individuals carrying the
      two alleles of the CCR5Delta32 mutation (CCR5(-/-)) has rarely been reported, but
      how the virus overcomes the CCR5Delta32 protective effect in these cases has not
      been delineated. We have investigated this in 6 infected (HIV(+)) and 25 HIV(-)
      CCR5(-/-) individuals. CD4(+) T lymphocytes isolated from HIV(-) CCR5(-/-)
      peripheral blood mononuclear cells (PBMCs) showed lower levels of CXCR4
      expression that correlated with lower X4 Env-mediated fusion. Endogenous
      CCR5Delta32 protein was detected in all HIV(-) CCR5(-/-) PBMC samples (n = 25)
      but not in four of six unrelated HIV(+) CCR5(-/-) PBMC samples. Low levels were
      detected in another two HIV(+) CCR5(-/-) PBMC samples. The expression of
      adenovirus 5 (Ad5)-encoded CCR5Delta32 protein restored the protective effect in
      PBMCs from three HIV(+) CCR5(-/-) individuals but failed to restore the
      protective effect in PBMCs isolated from another three HIV(+) CCR5(-/-)
      individuals. In the latter samples, pulse-chase analyses demonstrated the
      disappearance of endogenous Ad5-encoded CCR5Delta32 protein and the accumulation
      of Ad5-encoded CCR5 during the chase periods. PBMCs isolated from CCR5(-/-)
      individuals showed resistance to primary X4 but were readily infected by a lab
      adapted X4 strain. Low levels of Ad5-encoded CCR5Delta32 protein conferred
      resistance to primary X4 but not to lab-adapted X4 virus. These data provide
      strong support for the hypothesis that the CCR5Delta32 protein actively confers
      resistance to HIV-1 in vivo and suggest that the loss or reduction of CCR5Delta32
      protein expression may account for HIV-1 infection of CCR5(-/-) individuals. The
      results also suggest that other cellular or virally induced factors may be
      involved in the stability of CCR5Delta32 protein.

PMID- 17522202
TI  - Cytomegalovirus destruction of focal adhesions revealed in a high-throughput
      Western blot analysis of cellular protein expression.
AB  - Human cytomegalovirus (HCMV) systematically manages the expression of cellular
      functions, rather than exerting the global shutoff of host cell protein synthesis
      commonly observed with other herpesviruses during the lytic cycle. While
      microarray technology has provided remarkable insights into viral control of the
      cellular transcriptome, HCMV is known to encode multiple mechanisms for
      posttranscriptional and post-translation regulation of cellular gene expression.
      High-throughput Western blotting (BD Biosciences Powerblot technology) with 1,009
      characterized antibodies was therefore used to analyze and compare the effects of
      infection with attenuated high-passage strain AD169 and virulent low-passage
      strain Toledo at 72 hpi across gels run in triplicate for each sample. Six
      hundred ninety-four proteins gave a positive signal in the screen, of which 68
      from strain AD169 and 71 from strain Toledo were defined as being either
      positively or negatively regulated by infection with the highest level of
      confidence (BD parameters). In follow-up analyses, a subset of proteins was
      selected on the basis of the magnitude of the observed effect or their potential
      to contribute to defense against immune recognition. In analyses performed at 24,
      72, and 144 hpi, connexin 43 was efficiently downregulated during HCMV infection,
      implying a breakdown of intercellular communication. Mitosis-associated protein
      Eg-5 was found to be differentially upregulated in the AD169 and Toledo strains
      of HCMV. Focal adhesions link the actin cytoskeleton to the extracellular matrix
      and have key roles in initiating signaling pathways and substrate adhesion and
      regulating cell migration. HCMV suppressed expression of the focal-adhesion
      associated proteins Hic-5, paxillin, and alpha-actinin. Focal adhesions were
      clearly disrupted in HCMV-infected fibroblasts, with their associated
      intracellular and extracellular proteins being dispersed. Powerblot shows
      potential for rapid screening of the cellular proteome during HCMV infection.

PMID- 17522204
TI  - Lambda interferon (IFN-lambda) in serum is decreased in hantavirus-infected
      patients, and in vitro-established infection is insensitive to treatment with all
      IFNs and inhibits IFN-gamma-induced nitric oxide production.
AB  - Hantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus
      cardiopulmonary syndrome (HCPS), are known to be sensitive to nitric oxide (NO)
      and to pretreatment with type I and II interferons (alpha interferon [IFN
      alpha]/IFN-beta and IFN-gamma, respectively). Elevated serum levels of NO and IFN
      gamma have been observed in HFRS patients, but little is known regarding the
      systemic levels of other IFNs and the possible effects of hantaviruses on innate
      antiviral immune responses. In Puumala virus-infected HFRS patients (n = 18), we
      report that the levels of IFN-alpha and IFN-beta are similar, whereas the level
      of IFN-lambda (type III IFN) is significantly decreased, during acute (day of
      hospitalization) compared to the convalescent phase. The possible antiviral
      effects of IFN-lambda on the prototypic hantavirus Hantaan virus (HTNV)
      replication was then investigated. Pretreatment of A549 cells with IFN-lambda
      alone inhibited HTNV replication, and IFN-lambda combined with IFN-gamma induced
      additive antiviral effects. We then studied the effect of postinfection treatment
      with IFNs. Interestingly, an already-established HTNV infection was insensitive
      to subsequent IFN-alpha, -beta, -gamma, and -lambda stimulation, and HTNV
      infected cells produced less NO compared to noninfected cells when stimulated
      with IFN-gamma and IL-1beta. Furthermore, less phosphorylated STAT1 after IFN
      treatment was observed in the nuclei of infected cells than in those of
      noninfected cells. The results suggest that hantavirus can interfere with the
      activation of antiviral innate immune responses in patients and inhibit the
      antiviral effects of all IFNs. We believe that future studies addressing the
      mechanisms by which hantaviruses interfere with the activation and shaping of
      immune responses may bring more knowledge regarding HFRS and HCPS pathogenesis.

PMID- 17522203
TI  - Studying hepatitis C virus: making the best of a bad virus.

PMID- 17522205
TI  - Major neutralizing sites on vaccinia virus glycoprotein B5 are exposed
      differently on variola virus ortholog B6.
AB  - Immunization against smallpox (variola virus) with Dryvax, a live vaccinia virus
      (VV), was effective, but now safety is a major concern. To overcome this issue,
      subunit vaccines composed of VV envelope proteins from both forms of infectious
      virions, including the extracellular enveloped virion (EV) protein B5, are being
      developed. However, since B5 has 23 amino acid differences compared with its B6
      variola virus homologue, B6 might be a better choice for such a strategy.
      Therefore, we compared the properties of both proteins using a panel of
      monoclonal antibodies (MAbs) to B5 that we had previously characterized and
      grouped according to structural and functional properties. The B6 gene was
      obtained from the Centers for Disease Control and Prevention, and the ectodomain
      was cloned and expressed in baculovirus as previously done with B5, allowing us
      to compare the antigenic properties of the proteins. Polyclonal antibodies to B5
      or B6 cross-reacted with the heterologous protein, and 16 of 26 anti-B5 MAbs
      cross-reacted with B6. Importantly, 10 anti-B5 MAbs did not cross-react with B6.
      Of these, three have important anti-VV biologic properties, including their
      ability to neutralize EV infectivity and block comet formation. Here, we found
      that one of these three MAbs protected mice from a lethal VV challenge by passive
      immunization. Thus, epitopes that are present on B5 but not on B6 would generate
      an antibody response that would not recognize B6. Assuming that B6 contains
      similar variola virus-specific epitopes, our data suggest that a subunit vaccine
      using the variola virus homologues might exhibit improved protective efficacy
      against smallpox.

PMID- 17522206
TI  - Chicken heat shock protein 90 is a component of the putative cellular receptor
      complex of infectious bursal disease virus.
AB  - Infectious bursal disease virus (IBDV) causes a highly contagious disease in
      young chicks and leads to significant economic losses in the poultry industry.
      The capsid protein VP2 of IBDV plays an important role in virus binding and cell
      recognition. VP2 forms a subviral particle (SVP) with immunogenicity similar to
      that of the IBDV capsid. In the present study, we first showed that SVP could
      inhibit IBDV infection to an IBDV-susceptible cell line, DF-1 cells, in a dose
      dependent manner. Second, the localizations of the SVP on the surface of DF-1
      cells were confirmed by fluorescence microscopy, and the specific binding of the
      SVP to DF-1 cells occurred in a dose-dependent manner. Furthermore, the
      attachment of SVP to DF-1 cells was inhibited by an SVP-induced neutralizing
      monoclonal antibody against IBDV but not by denatured-VP2-induced polyclonal
      antibodies. Third, the cellular factors in DF-1 cells involved in the attachment
      of SVP were purified by affinity chromatography using SVP bound on the
      immobilized Ni(2+) ions. A dominant factor was identified as being chicken heat
      shock protein 90 (Hsp90) (cHsp90) by mass spectrometry. Results of biotinylation
      experiments and indirect fluorescence assays indicated that cHsp90 is located on
      the surface of DF-1 cells. Virus overlay protein binding assays and far-Western
      assays also concluded that cHsp90 interacts with IBDV and SVP, respectively.
      Finally, both Hsp90 and anti-Hsp90 can inhibit the infection of DF-1 cells by
      IBDV. Taken together, for the first time, our results suggest that cHsp90 is part
      of the putative cellular receptor complex essential for IBDV entry into DF-1
      cells.

PMID- 17522207
TI  - Human immunodeficiency virus type 1 assembly, budding, and cell-cell spread in T
      cells take place in tetraspanin-enriched plasma membrane domains.
AB  - Human immunodeficiency virus type-1 (HIV-1) egress from infected CD4+ T cells is
      thought to be via assembly and budding at the plasma membrane and may involve
      components of the T-cell secretory apparatus, including tetraspanins. However,
      many studies on HIV-1 assembly have examined the trafficking of viral proteins in
      isolation, and most have used immortalized epithelial, fibroblastic, or
      hematopoietic cell lines that may not necessarily reflect natural infection of
      susceptible T cells. Here we have used immunofluorescence and cryoimmunoelectron
      microscopy (CEM) to examine protein transport during HIV-1 assembly in
      productively infected Jurkat CD4+ T cells and primary CD4+ T cells. The HIV-1
      envelope glycoprotein (Env) and the core protein (Gag) colocalize strongly with
      CD63 and CD81 and less strongly with CD9, whereas no colocalization was seen
      between Env or Gag and the late endosome/lysosomal marker Lamp2. CEM revealed
      incorporation of CD63 and CD81 but not Lamp2 into virions budding at the plasma
      membrane, and this was supported by immunoprecipitation studies, confirming that
      HIV-1 egress in T cells is trafficked via tetraspanin-enriched membrane domains
      (TEMs) that are distinct from lysosomal compartments. CD63, CD81, and, to a
      lesser extent, CD9 were recruited to the virological synapse (VS), and antibodies
      against these tetraspanins reduced VS formation. We propose that HIV-1 promotes
      virus assembly and cell-cell transfer in T cells by targeting plasma membrane
      TEMs.

PMID- 17522208
TI  - Coupled translation of the second open reading frame of M2 mRNA is sequence
      dependent and differs significantly within the subfamily Pneumovirinae.
AB  - Coupled translation, first described in the M2 gene of pneumovirus respiratory
      syncytial virus (RSV), is an alternative mechanism of translational initiation in
      which the ribosomes which translate the first (M2-1) open reading frame (ORF)
      move a short distance upstream after termination and reinitiate translation from
      a second (M2-2) overlapping ORF. Here, we show that the same mechanism occurs in
      two closely related viruses, avian pneumovirus (APV) and pneumonia virus of mice
      (PVM), although with markedly different efficiencies. To identify the reasons for
      the variation in efficiency of coupled expression between RSV and APV, we used
      chimeric M2-1 genes containing different lengths of the M2-1 ORF from each virus.
      An essential component allowing coupled expression in the chimeras was a segment
      from the RSV M2-1 coding region containing a high degree of secondary structure.
      Additional sequences at the 5' end of the RSV M2-1 ORF also promoted coupled
      translation when the region with high levels of secondary structure was present.
      These data indicate that at least two distant parts of the mRNA transcript,
      together with a suitable overlapping region, are involved in the coupling
      process. Replacement of the last 102 nucleotides of the RSV M2-1 ORF with the
      equivalent APV sequence showed identical levels of coupled translation. Thus, the
      overlapping region can direct the ribosome back onto the start codon of the
      second ORF while the upstream coding sequence of the M2-1 ORF determines the
      levels of coupled expression.

PMID- 17522209
TI  - Inhibition of interferon regulatory factor 7 (IRF7)-mediated interferon signal
      transduction by the Kaposi's sarcoma-associated herpesvirus viral IRF homolog
      vIRF3.
AB  - Upon viral infection, the major defense mounted by the host immune system is
      activation of the interferon (IFN)-mediated antiviral pathway that is mediated by
      IFN regulatory factors (IRFs). In order to complete their life cycle, viruses
      must modulate the host IFN-mediated immune response. Kaposi's sarcoma-associated
      herpesvirus (KSHV), a human tumor-inducing herpesvirus, has developed a unique
      mechanism for antagonizing cellular IFN-mediated antiviral activity by
      incorporating viral homologs of the cellular IRFs, called vIRFs. Here, we report
      a novel immune evasion mechanism of KSHV vIRF3 to block cellular IRF7-mediated
      innate immunity in response to viral infection. KSHV vIRF3 specifically interacts
      with either the DNA binding domain or the central IRF association domain of IRF7,
      and this interaction leads to the inhibition of IRF7 DNA binding activity and,
      therefore, suppression of alpha interferon (IFN-alpha) production and IFN
      mediated immunity. Remarkably, the central 40 amino acids of vIRF3, containing
      the double alpha helix motifs, are sufficient not only for binding to IRF7, but
      also for inhibiting IRF7 DNA binding activity. Consequently, the expression of
      the double alpha helix motif-containing peptide effectively suppresses IRF7
      mediated IFN-alpha production. This demonstrates a remarkably efficient means of
      viral avoidance of host antiviral activity.

PMID- 17522210
TI  - Early blood profiles of virus infection in a monkey model for Lassa fever.
AB  - Acute arenavirus disease in primates, like Lassa hemorrhagic fever in humans,
      begins with flu-like symptoms and leads to death approximately 2 weeks after
      infection. Our goal was to identify molecular changes in blood that are related
      to disease progression. Rhesus macaques (Macaca mulatta) infected intravenously
      with a lethal dose of lymphocytic choriomeningitis virus (LCMV) provide a model
      for Lassa virus infection of humans. Blood samples taken before and during the
      course of infection were used to monitor gene expression changes that paralleled
      disease onset. Changes in blood showed major disruptions in eicosanoid, immune
      response, and hormone response pathways. Approximately 12% of host genes alter
      their expression after LCMV infection, and a subset of these genes can
      discriminate between virulent and non-virulent LCMV infection. Major
      transcription changes have been given preliminary confirmation by quantitative
      PCR and protein studies and will be valuable candidates for future validation as
      biomarkers for arenavirus disease.

PMID- 17522211
TI  - Human immunodeficiency virus type 1 Vif inhibits packaging and antiviral activity
      of a degradation-resistant APOBEC3G variant.
AB  - Human immunodeficiency virus type 1 (HIV-1) Vif counteracts the antiviral
      activity of the human cytidine deaminase APOBEC3G (APO3G) by inhibiting its
      incorporation into virions. This has been attributed to the Vif-induced
      degradation of APO3G by cytoplasmic proteasomes. We recently demonstrated that
      although APO3G has a natural tendency to form RNA-dependent homo-multimers,
      multimerization was not essential for encapsidation into HIV-1 virions or
      antiviral activity. We now demonstrate that a multimerization-defective APO3G
      variant (APO3G C97A) is able to assemble into RNase-sensitive high-molecular-mass
      (HMM) complexes, suggesting that homo-multimerization of APO3G and assembly into
      HMM complexes are unrelated RNA-dependent processes. Interestingly, APO3G C97A
      was highly resistant to Vif-induced degradation even though the two proteins were
      found to interact in coimmunoprecipitation experiments and exhibited partial
      colocalization in transfected HeLa cells. Surprisingly, encapsidation and
      antiviral activity of APO3G C97A were both inhibited by Vif despite resistance to
      degradation. These results demonstrate that targeting of APO3G to proteasome
      degradation and interference with viral encapsidation are distinct functional
      properties of Vif.

PMID- 17522212
TI  - Matrix fibronectin binds gammaretrovirus and assists in entry: new light on viral
      infections.
AB  - A major entry route for the gammaretrovirus amphotropic murine leukemia virus (A
      MLV) into NIH 3T3 fibroblasts is via caveola-dependent endocytosis. However,
      during the infection time, few viral particles can be observed intracellularly.
      Analyzing the dynamics of the A-MLV infection process by using total internal
      reflection fluorescence microscopy, we show that the majority of viruses are
      extracellular and bound to the fibronectin matrix. Moreover, the amounts of bound
      virus and of fibronectin correlated. Using confocal microscopy, nanoparticles
      targeted to fibronectin by a III1C-fibronectin fragment or anti-fibronectin
      antibody were detected intracellularly in NIH 3T3 cells; unconjugated
      nanoparticles neither bound to cells nor were detectable intracellularly.
      Furthermore, A-MLV colocalized intracellularly with the fibronectin-targeted
      nanoparticles, suggesting that they were taken up by the same cellular pathway.
      Both A-MLV entry and fibronectin turnover depend on caveolar endocytosis, and we
      found that inhibiting viral binding to the extracellular NIH 3T3 fibronectin
      matrix dramatically reduced A-MLV infection, indeed, showing an active role of
      fibronectin in infection. We suggest that binding to the cellular fibronectin
      matrix provides a new mechanism by which viruses can enter cells.

PMID- 17522213
TI  - Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1
      mimics Epstein-Barr virus EBNA1 immune evasion through central repeat domain
      effects on protein processing.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8 [HHV8]) and
      Epstein-Barr virus (EBV/HHV4) are distantly related gammaherpesviruses causing
      tumors in humans. KSHV latency-associated nuclear antigen 1 (LANA1) is
      functionally similar to the EBV nuclear antigen-1 (EBNA1) protein expressed
      during viral latency, although they have no amino acid similarities. EBNA1
      escapes cytotoxic lymphocyte (CTL) antigen processing by inhibiting its own
      proteosomal degradation and retarding its own synthesis to reduce defective
      ribosomal product processing. We show here that the LANA1 QED-rich central repeat
      (CR) region, particularly the CR2CR3 subdomain, also retards LANA1 synthesis and
      markedly enhances LANA1 stability in vitro and in vivo. LANA1 isoforms have half
      lives greater than 24 h, and fusion of the LANA1 CR2CR3 domain to a destabilized
      heterologous protein markedly decreases protein turnover. Unlike EBNA1, the LANA1
      CR2CR3 subdomain retards translation regardless of whether it is fused to the 5'
      or 3' end of a heterologous gene construct. Manipulation of sequence order,
      orientation, and composition of the CR2 and CR3 subdomains suggests that specific
      peptide sequences rather than RNA structures are responsible for synthesis
      retardation. Although mechanistic differences exist between LANA1 and EBNA1, the
      primary structures of both proteins have evolved to minimize provoking CTL immune
      responses. Simple strategies to eliminate these viral inhibitory regions may
      markedly improve vaccine effectiveness by maximizing CTL responses.

PMID- 17522214
TI  - Adaptation of Borna disease virus to new host species attributed to altered
      regulation of viral polymerase activity.
AB  - Borna disease virus (BDV) can persistently infect the central nervous system of a
      broad range of mammalian species. Mice are resistant to infections with primary
      BDV isolates, but certain laboratory strains can be adapted to replicate in mice.
      We determined the molecular basis of adaptation by studying mutations acquired by
      a cDNA-derived BDV strain during one brain passage in rats and three passages in
      mice. The adapted virus propagated efficiently in mouse brains and induced
      neurological disease. Its genome contained seven point mutations, three of which
      caused amino acid changes in the L polymerase (L1116R and N1398D) and in the
      polymerase cofactor P (R66K). Recombinant BDV carrying these mutations either
      alone or in combination all showed enhanced multiplication speed in Vero cells,
      indicating improved intrinsic viral polymerase activity rather than adaptation to
      a mouse-specific factor. Mutations R66K and L1116R, but not N1398D, conferred
      replication competence of recombinant BDV in mice if introduced individually.
      Virus propagation in mouse brains was substantially enhanced if both L mutations
      were present simultaneously, but infection remained mostly nonsymptomatic. Only
      if all three amino acid substitutions were combined did BDV replicate vigorously
      and induce early disease in mice. Interestingly, the virulence-enhancing effect
      of the R66K mutation in P could be attributed to reduced negative regulation of
      polymerase activity by the viral X protein. Our data demonstrate that BDV
      replication competence in mice is mediated by the polymerase complex rather than
      the viral envelope and suggest that altered regulation of viral gene expression
      can favor adaptation to new host species.

PMID- 17522215
TI  - Epstein-Barr virus induces MCP-1 secretion by human monocytes via TLR2.
AB  - Epstein-Barr virus (EBV) is a gammaherpesvirus infecting the majority of the
      human adult population in the world. TLR2, a member of the Toll-like receptor
      (TLR) family, has been implicated in the immune responses to different viruses
      including members of the herpesvirus family, such as human cytomegalovirus,
      herpes simplex virus type 1, and varicella-zoster virus. In this report, we
      demonstrate that infectious and UV-inactivated EBV virions lead to the activation
      of NF-kappaB through TLR2 using HEK293 cells cotransfected with TLR2-expressing
      vector along with NF-kappaB-Luc reporter plasmid. NF-kappaB activation in HEK293
      TLR2 cells (HEK293 cells transfected with TLR2) by EBV was not enhanced by the
      presence of CD14. The effect of EBV was abrogated by pretreating HEK293-TLR2
      cells with blocking anti-TLR2 antibodies or by preincubating viral particles with
      neutralizing anti-EBV antibodies 72A1. In addition, EBV infection of primary
      human monocytes induced the release of MCP-1 (monocyte chemotactic protein 1),
      and the use of small interfering RNA targeting TLR2 significantly reduced such a
      chemokine response to EBV. Taken together, these results indicate that TLR2 may
      be an important pattern recognition receptor in the immune response directed
      against EBV infection.

PMID- 17522216
TI  - Identification of two distinct human immunodeficiency virus type 1 Vif
      determinants critical for interactions with human APOBEC3G and APOBEC3F.
AB  - Human cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) inhibit replication
      of Vif-deficient human immunodeficiency virus type 1 (HIV-1). HIV-1 Vif overcomes
      these host restriction factors by binding to them and inducing their proteasomal
      degradation. The Vif-A3G and Vif-A3F interactions are attractive targets for
      antiviral drug development because inhibiting the interactions could allow the
      host defense mechanism to control HIV-1 replication. It was recently reported
      that the Vif amino acids D(14)RMR(17) are important for functional interaction
      and degradation of the previously identified Vif-resistant mutant of A3G (D128K
      A3G). However, the Vif determinants important for functional interaction with A3G
      and A3F have not been fully characterized. To identify these determinants, we
      performed an extensive mutational analysis of HIV-1 Vif. Our analysis revealed
      two distinct Vif determinants, amino acids Y(40)RHHY(44) and D(14)RMR(17), which
      are essential for binding to A3G and A3F, respectively. Interestingly, mutation
      of the A3G-binding region increased Vif's ability to suppress A3F. Vif binding to
      D128K-A3G was also dependent on the Y(40)RHHY(44) region but not the D(14)RMR(17)
      region. Consistent with previous observations, subsequent neutralization of the
      D128K-A3G antiviral activity required substitution of Vif determinant
      D(14)RMR(17) with SEMQ, similar to the SERQ amino acids in simian
      immunodeficiency virus SIV(AGM) Vif, which is capable of neutralizing D128K-A3G.
      These studies are the first to clearly identify two distinct regions of Vif that
      are critical for independent interactions with A3G and A3F. Pharmacological
      interference with the Vif-A3G or Vif-A3F interactions could result in potent
      inhibition of HIV-1 replication by the APOBEC3 proteins.

PMID- 17522217
TI  - The N terminus of the herpes simplex virus type 1 triplex protein, VP19C, cannot
      be detected on the surface of the capsid shell by using an antibody
      (hemagglutinin) epitope tag.
AB  - The herpes simplex virus (HSV) triplex is a complex of three protein subunits,
      VP19C and a dimer of VP23 that is essential for capsid assembly. We have derived
      HSV-1 recombinant viruses that contain monomeric red fluorescent protein (mRFP1),
      a Flu hemagglutinin (HA) epitope, and a six-histidine tag fused to the amino
      terminus of VP19C. These viruses were capable of growth on Vero cells, indicating
      that the amino terminus of VP19C could tolerate these fusions. By use of
      immunoelectron microscopy methods, capsids that express VP19C-mRFP but not VP19C
      HA were labeled with gold particles when incubated with the corresponding
      antibody. Our conclusion from the data is that a large tag at the N terminus of
      VP19C was sufficiently exposed on the capsid surface for polyclonal antibody
      reactivity, while the small HA epitope was inaccessible to the antibody. These
      data indicate that an epitope tag at the amino terminus of VP19C is not exposed
      at the capsid surface for reactivity to its antibody.

PMID- 17522218
TI  - The neutralizing activity of anti-hepatitis C virus antibodies is modulated by
      specific glycans on the E2 envelope protein.
AB  - Hepatitis C virus (HCV) envelope glycoproteins are highly glycosylated, with up
      to 5 and 11 N-linked glycans on E1 and E2, respectively. Most of the
      glycosylation sites on HCV envelope glycoproteins are conserved, and some of the
      glycans associated with these proteins have been shown to play an essential role
      in protein folding and HCV entry. Such a high level of glycosylation suggests
      that these glycans can limit the immunogenicity of HCV envelope proteins and
      restrict the binding of some antibodies to their epitopes. Here, we investigated
      whether these glycans can modulate the neutralizing activity of anti-HCV
      antibodies. HCV pseudoparticles (HCVpp) bearing wild-type glycoproteins or
      mutants at individual glycosylation sites were evaluated for their sensitivity to
      neutralization by antibodies from the sera of infected patients and anti-E2
      monoclonal antibodies. While we did not find any evidence that N-linked glycans
      of E1 contribute to the masking of neutralizing epitopes, our data demonstrate
      that at least three glycans on E2 (denoted E2N1, E2N6, and E2N11) reduce the
      sensitivity of HCVpp to antibody neutralization. Importantly, these three glycans
      also reduced the access of CD81 to its E2 binding site, as shown by using a
      soluble form of the extracellular loop of CD81 in inhibition of entry. These data
      suggest that glycans E2N1, E2N6, and E2N11 are close to the binding site of CD81
      and modulate both CD81 and neutralizing antibody binding to E2. In conclusion,
      this work indicates that HCV glycans contribute to the evasion of HCV from the
      humoral immune response.

PMID- 17522219
TI  - The H5N1 influenza virus NS genes selected after 1998 enhance virus replication
      in mammalian cells.
AB  - The NS1A proteins of human influenza A viruses bind CPSF30, a cellular factor
      required for the processing of cellular pre-mRNAs, thereby inhibiting the
      production of all cellular mRNAs, including beta interferon mRNA. Here we show
      that the NS1A protein of the pathogenic H5N1 influenza A/Hong Kong/483/97 (HK97)
      virus isolated from humans has an intrinsic defect in CPSF30 binding. It does not
      bind CPSF30 in vitro and causes high beta interferon mRNA production and reduced
      virus replication in MDCK cells when expressed in a recombinant virus in which
      the other viral proteins are encoded by influenza A/Udorn/72. We traced this
      defect to the identities of amino acids 103 and 106 in the HK97 NS1A protein,
      which differ from the consensus amino acids, F and M, respectively, found in the
      NS1A proteins of almost all human influenza A virus strains. X-ray
      crystallography has shown that F103 and M106, which are not part of the CPSF30
      binding pocket of the NS1A protein, stabilize the NS1A-CPSF30 complex. In
      contrast to the HK97 NS1A protein, the NS1A proteins of H5N1 viruses isolated
      from humans after 1998 contain F103 and M106 and hence bind CPSF30 in vitro and
      do not attenuate virus replication. The HK97 NS1A protein is less attenuating
      when expressed in a virus that also encodes the other internal HK97 proteins and
      under these conditions binds to CPSF30 to a substantial extent in vivo.
      Consequently, these internal HK97 proteins largely compensate for the absence of
      F103 and M106, presumably by stabilizing the NS1A-CPSF30 complex.

PMID- 17522220
TI  - A recombinant human monoclonal antibody to human metapneumovirus fusion protein
      that neutralizes virus in vitro and is effective therapeutically in vivo.
AB  - Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is a
      major cause of lower-respiratory-tract disease. hMPV is associated with more
      severe disease in infants and persons with underlying medical conditions. Animal
      studies have shown that the hMPV fusion (F) protein alone is capable of inducing
      protective immunity. Here, we report the use of phage display technology to
      generate a fully human monoclonal antibody fragment (Fab) with biological
      activity against hMPV. Phage antibody libraries prepared from human donor tissues
      were selected against recombinant hMPV F protein with multiple rounds of panning.
      Recombinant Fabs then were expressed in bacteria, and supernatants were screened
      by enzyme-linked immunosorbent assay and immunofluorescent assays. A number of
      Fabs that bound to hMPV F were isolated, and several of these exhibited
      neutralizing activity in vitro. Fab DS7 neutralized the parent strain of hMPV
      with a 60% plaque reduction activity of 1.1 mug/ml and bound to hMPV F with an
      affinity of 9.8 x10(-10) M, as measured by surface plasmon resonance. To test the
      in vivo activity of Fab DS7, groups of cotton rats were infected with hMPV and
      given Fab intranasally 3 days after infection. Nasal turbinates and lungs were
      harvested on day 4 postinfection and virus titers determined. Animals treated
      with Fab DS7 exhibited a >1,500-fold reduction in viral titer in the lungs, with
      a modest 4-fold reduction in the nasal tissues. There was a dose-response
      relationship between the dose of DS7 and virus titer. Human Fab DS7 may have
      prophylactic or therapeutic potential against severe hMPV infection.

PMID- 17522221
TI  - Phylogenetic analysis and structural predictions of human adenovirus penton
      proteins as a basis for tissue-specific adenovirus vector design.
AB  - The penton base is a major capsid protein of human adenoviruses (HAdV) which
      forms the vertices of the capsid and interacts with hexon and fiber protein. Two
      hypervariable loops of the penton are exposed on the capsid surface. Sequences of
      these and 300 adjacent amino acid residues of all 51 HAdV and closely related
      simian adenoviruses were studied. Adjacent sequences and predicted overall
      secondary structure were conserved. Phylogenetic analysis revealed clustering
      corresponding to the HAdV species and recombination events in the origin of HAdV
      prototypes. All HAdV except serotypes 40 and 41 of species F exhibited an
      integrin binding RGD motif in the second loop. The lengths of the loops (HVR1 and
      RGD loops) varied significantly between HAdV species with the longest RGD loop
      observed in species C and the longest HVR1 in species B. Long loops may permit
      the insertion of motifs that modify tissue tropism. Genetic analysis of HAdV
      prime strain p17'H30, a neutralization variant of HAdV-D17, indicated the
      significance of nonhexon neutralization epitopes for HAdV immune escape. Fourteen
      highly conserved motifs of the penton base were analyzed by site-directed
      mutagenesis of HAdV-D8 and tested for sustained induction of early cytopathic
      effects. Thus, three new motifs essential for penton base function were
      identified additionally to the RGD site, which interacts with a secondary
      cellular receptor responsible for internalization. Therefore, our penton primary
      structure data and secondary structure modeling in combination with the recently
      published fiber knob sequences may permit the rational design of tissue-specific
      adenoviral vectors.

PMID- 17522222
TI  - Pretreatment sequence diversity differences in the full-length hepatitis C virus
      open reading frame correlate with early response to therapy.
AB  - Pegylated alpha interferon and ribavirin therapy for hepatitis C virus (HCV)
      genotype 1 infection fails for half of Caucasian American patients (CA) and more
      often for African Americans (AA). The reasons for these low response rates are
      unknown. HCV is highly genetically variable, but it is unknown how this
      variability affects response to therapy. To assess effects of viral diversity on
      response to therapy, the complete pretreatment genotype 1 HCV open reading frame
      was sequenced using samples from 94 participants in the Virahep-C study.
      Sequences from patients with >3.5 log declines in viral RNA levels by day 28
      (marked responders) were more variable than those from patients with declines of
      <1.4 log (poor responders) in NS3 and NS5A for genotype 1a and in core and NS3
      for genotype 1b. These correlations remained when all T-cell epitopes were
      excluded, indicating that these differences were not due to differential immune
      selection. When the sequences were compared by race of the patients, higher
      diversity in CA patients was found in E2 and NS2 but only for genotype 1b. Core,
      NS3, and NS5A can block the action of alpha interferon in vitro; hence, these
      genetic patterns are consistent with multiple amino acid variations independently
      impairing the function of HCV proteins that counteract interferon responses in
      humans, resulting in HCV strains with variable sensitivity to therapy. No
      evidence was found for novel HCV strains in the AA population, implying that AA
      patients may be infected with a higher proportion of the same resistant strains
      that are found in CA patients.

PMID- 17522223
TI  - Identification of the optimal DC-SIGN binding site on human immunodeficiency
      virus type 1 gp120.
AB  - Human immunodeficiency virus type 1 (HIV-1) envelope (gp120) binding to DC-SIGN,
      a C-type lectin that can facilitate HIV infection in cis and in trans, is largely
      dependent on high-mannose-content moieties. Here, we delineate the N-linked
      glycosylation (N-glycan) sites in gp120 that contribute to optimal DC-SIGN
      binding. Soluble DC-SIGN was able to block 2G12 binding to gp120, but not vice
      versa, suggesting that DC-SIGN binds to a more flexible combination of N-glycans
      than 2G12. Consistent with this observation, HIV strain JRCSF gp120 prebound to
      2G12 was 10-fold more sensitive to mannan competition than gp120 that was not
      prebound in a DC-SIGN cell surface binding assay. The analysis of multiple mutant
      forms of the 2G12 epitope revealed one triple glycosylation mutant form, termed
      134mut (carrying N293Q, N382Q, and N388Q mutations), that exhibited a significant
      increase in sensitivity to both mannan competition and endoglycosidase H
      digestion compared to that of the 124mut form (carrying N293Q, N328Q, and N388Q
      mutations) and wild-type gp120 in a DC-SIGN binding assay. Importantly, no such
      differences were observed when binding to Galanthus nivalis was assessed. The
      134mut form of gp120 also exhibited decreased binding to DC-SIGN in the context
      of native envelope spikes on a virion, and virus bearing 134mut exhibited less
      efficient DC-SIGN-mediated infection in trans. Significantly, 124mut and 134mut
      differed by only one glycosylation site mutation in each construct, and both
      124mut and 134mut viruses exhibited wild-type levels of infectivity when used in
      a direct infection assay. In summary, while DC-SIGN can bind to a flexible
      combination of N-glycans on gp120, its optimal binding site overlaps with
      specific N-glycans within the 2G12 epitope. Conformationally intact envelopes
      that are DC-SIGN binding deficient can be used to probe the in vivo biological
      functions of DC-SIGN.

PMID- 17522224
TI  - Natural variation in the V3 crown of human immunodeficiency virus type 1 affects
      replicative fitness and entry inhibitor sensitivity.
AB  - Natural polymorphisms in the heterogeneous human immunodeficiency virus type 1
      (HIV-1) envelope glycoprotein may have an impact on both sensitivity to entry
      inhibitors and viral replicative fitness. Of significant interest is variation in
      the V3 crown due to its involvement in direct engagement with the coreceptor. Two
      positions in the crown (318 and 319) appear to be important in determining
      intrinsic susceptibility to multiple entry inhibitors. Thus, we evaluated a
      series of natural polymorphisms at positions 318 and 319 in three distinct CCR5
      tropic envelope genetic backgrounds to address their role in replicative fitness
      and sensitivity to entry inhibitors. Change at position 319 to each of the three
      major consensus amino acids (A, T, and R) resulted in variation in sensitivity to
      entry inhibitors and altered replicative fitness, but the effects of any one
      amino acid depended on the envelope context. Change of the nearly invariant
      tyrosine at position 318 to a rare arginine resulted in increased sensitivity to
      entry inhibitors and decreased replicative fitness independent of envelope
      context. Polymorphisms in the V3 crown that showed increased susceptibility to
      entry inhibitors also exhibited decreased entry efficiency, replicative fitness
      in primary peripheral blood mononuclear cells, and ability to replicate in
      primary macrophages. These findings suggest that differences in coreceptor
      affinity and/or avidity may underlie these phenotypic characteristics.

PMID- 17522225
TI  - Expression of extremely low levels of thymidine kinase from an acyclovir
      resistant herpes simplex virus mutant supports reactivation from latently
      infected mouse trigeminal ganglia.
AB  - A single-cytosine-deletion in the herpes simplex virus gene encoding thymidine
      kinase (TK) was previously found in an acyclovir-resistant clinical isolate. A
      laboratory strain engineered to carry this mutation did not generate sufficient
      TK activity for detection by plaque autoradiography, which detected 0.25% wild
      type activity. However, a drug sensitivity assay suggested that extremely low
      levels of TK are generated by this virus. The virus was estimated to express
      0.09% of wild-type TK activity via a ribosomal frameshift 24 nucleotides upstream
      of the mutation. Remarkably, this appeared to be sufficient active TK to support
      a low level of reactivation from latently infected mouse trigeminal ganglia.

PMID- 17522226
TI  - Human parainfluenza viruses hPIV1 and hPIV3 bind oligosaccharides with alpha2-3
      linked sialic acids that are distinct from those bound by H5 avian influenza
      virus hemagglutinin.
AB  - We investigated the binding of human parainfluenza virus types 1 and 3 (hPIV1 and
      hPIV3, respectively) to the glycan array of the Consortium for Functional
      Glycomics and binding and their release from erythrocytes under conditions where
      neuraminidase is inactive or active. hPIV1 and hPIV3 bind modifications of
      Neu5Acalpha2-3Galbeta1-4GlcNAc, including the sialyl-Lewis(x) motif and
      structures containing 6-sulfogalactose. hPIV1 and hPIV3 thus bind typical N
      linked glycans, in contrast to avian influenza virus H5 hemagglutinin (J.
      Stevens, O. Blixt, T. M. Tumpey, J. K. Taubenberger, J. C. Paulson, and I. A.
      Wilson, Science 312:404-410, 2006), which binds less-common motifs. While the
      receptor is not the sole determinant of tropism, hPIV or H5 influenza virus
      infection of specific cells that express receptors may contribute to their
      different pathologies.

PMID- 17522227
TI  - Protein kinase PKR plays a stimulus- and virus-dependent role in apoptotic death
      and virus multiplication in human cells.
AB  - The protein kinase regulated by double-stranded RNA (dsRNA), PKR, is implicated
      in a range of biologic processes, including apoptotic death and interferon
      antiviral responses, based in part on studies with mouse cells genetically
      deficient in Pkr. To test the role of the PKR protein in human cells, an RNA
      interference silencing strategy was used to generate stable HeLa cell lines with
      less than 2% of the PKR protein (PKR deficient) compared to either parental or
      control knockdown HeLa lines. Phosphorylation of the alpha subunit of eukaryotic
      initiation factor 2 on serine 51 was not detectably increased in response to
      dsRNA in PKR-deficient HeLa cells but was elevated severalfold in PKR-sufficient
      cells. PKR-deficient cells displayed reduced dsRNA-induced apoptosis compared to
      PKR-sufficient cell lines, whereas tumor necrosis factor alpha (TNF-alpha)
      induced apoptosis was comparable between the HeLa lines. NF-kappaB was activated
      to a comparable extent in PKR-deficient and PKR-sufficient HeLa cells upon
      treatment with either dsRNA or TNF-alpha. The antiviral response against
      vesicular stomatitis virus was reduced in interferon-treated PKR-deficient
      compared to PKR-sufficient HeLa cells. However, the growth of two human viruses,
      adenovirus and reovirus, was unaffected by the PKR knockdown. Surprisingly, the
      yield of mutant adenovirus that fails to encode VAI RNA was not enhanced in PKR
      deficient cells, indicating the importance of host factors in addition to PKR in
      conferring the VAI RNA phenotype.

PMID- 17522228
TI  - Susceptibility of recently transmitted subtype B human immunodeficiency virus
      type 1 variants to broadly neutralizing antibodies.
AB  - The ability of the broadly neutralizing human immunodeficiency virus type 1 (HIV
      1) specific human monoclonal antibodies (MAbs) b12, 2G12, 2F5, and 4E10 to
      neutralize recently transmitted viruses has not yet been explored in detail. We
      investigated the neutralization sensitivity of subtype B HIV-1 variants obtained
      from four primary HIV infection cases and six transmission couples (four
      homosexual and two parenteral) to these MAbs. Sexually transmitted HIV-1 variants
      isolated within the first 2 months after seroconversion were generally sensitive
      to 2F5, moderately resistant to 4E10 and b12, and initially resistant but later
      more sensitive to 2G12 neutralization. In the four homosexual transmission
      couples, MAb neutralization sensitivity of HIV in recipients did not correlate
      with the MAb neutralization sensitivity of HIV from their source partners,
      whereas the neutralization sensitivity of donor and recipient viruses involved in
      parenteral transmission was more similar. For a fraction (11%) of the HIV-1
      variants analyzed here, neutralization by 2G12 could not be predicted by the
      presence of N-linked glycosylation sites previously described to be involved in
      2G12 binding. Resistance to 2F5 and 4E10 neutralization did also not correlate
      with mutations in the respective core epitopes. Overall, we observed that the
      neutralization resistance of recently transmitted subtype B HIV-1 variants was
      relatively high. Although 8 of 10 patients had viruses that were sensitive to
      neutralization by at least one of the four broadly neutralizing antibodies
      studied, 4 of 10 patients harbored at least one virus variant that seemed
      resistant to all four antibodies. Our results suggest that vaccine antigens that
      only elicit antibodies equivalent to b12, 2G12, 2F5, and 4E10 may not be
      sufficient to protect against all contemporary HIV-1 variants and that additional
      cross-neutralizing specificities need to be sought.

PMID- 17522229
TI  - The NS3 helicase and NS5B-to-3'X regions are important for efficient hepatitis C
      virus strain JFH-1 replication in Huh7 cells.
AB  - The JFH-1 strain of hepatitis C virus (HCV) is a genotype 2a strain that can
      replicate autonomously in Huh7 cells. The J6 strain is also a genotype 2a strain,
      but its full genomic RNA does not replicate in Huh7 cells. However, chimeric
      J6/JFH-1 RNA that has J6 structural-protein-coding regions and JFH-1
      nonstructural-protein-coding regions can replicate autonomously and produce
      infectious HCV particles. In order to determine the mechanisms underlying JFH-1
      RNA replication, we constructed various J6/JFH-1 chimeras and tested their RNA
      replication and virus particle production abilities in Huh7 cells. Via subgenomic
      RNA-replication assays, we found that both the JFH-1 NS5B-to-3'X (N5BX) and the
      NS3 helicase (N3H) regions are important for the replication of the J6CF
      replicon. We applied these results to full-length genomic RNA replication and
      analyzed replication using Northern blotting. We found that a chimeric J6 clone
      with JFH-1 N3H and N5BX could replicate autonomously but that a chimeric J6 clone
      with only JFH-1 N5BX had no replication ability. Finally, we tested the virus
      production abilities of these clones and found that a chimeric J6 clone with JFH
      1 N3H and N5BX could produce infectious HCV particles. In conclusion, the JFH-1
      NS3 helicase and NS5B-to-3'X regions are important for efficient replication and
      virus particle formation of HCV genotype 2a strains.

PMID- 17522230
TI  - Guinea pig-adapted foot-and-mouth disease virus with altered receptor recognition
      can productively infect a natural host.
AB  - We report that adaptation to infect the guinea pig did not modify the capacity of
      foot-and-mouth disease virus (FMDV) to kill suckling mice and to cause an acute
      and transmissible disease in the pig, an important natural host for this
      pathogen. Adaptive amino acid replacements (I(248)-->T in 2C, Q(44)-->R in 3A,
      and L(147)-->P in VP1), selected upon serial passages of a type C FMDV isolated
      from swine (biological clone C-S8c1) in the guinea pig, were maintained after
      virus multiplication in swine and suckling mice. However, the adaptive
      replacement L(147)-->P, next to the integrin-binding RGD motif at the GH loop in
      VP1, abolished growth of the virus in different established cell lines and
      modified its antigenicity. In contrast, primary bovine thyroid cell cultures
      could be productively infected by viruses with replacement L(147)-->P, and this
      infection was inhibited by antibodies to alphavbeta6 and by an FMDV-derived RGD
      containing peptide, suggesting that integrin alphavbeta6 may be used as a
      receptor for these mutants in the animal (porcine, guinea pig, and suckling mice)
      host. Substitution T(248)-->N in 2C was not detectable in C-S8c1 but was present
      in a low proportion of the guinea pig-adapted virus. This substitution became
      rapidly dominant in the viral population after the reintroduction of the guinea
      pig-adapted virus into pigs. These observations illustrate how the appearance of
      minority variant viruses in an unnatural host can result in the dominance of
      these viruses on reinfection of the original host species.

PMID- 17522231
TI  - Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into
      target cells expressing ACE2 with the cytoplasmic tail deleted.
AB  - The penetration of various viruses into host cells is accomplished by hijacking
      the host endocytosis machinery. In the case of severe acute respiratory syndrome
      coronavirus (SARS-CoV) infection, viral entry is reported to require a low pH in
      intracytoplasmic vesicles; however, little is known about how SARS-CoV invades
      such compartments. Here we demonstrate that SARS-CoV mainly utilizes the clathrin
      mediated endocytosis pathway for its entry to target cells by using infectious
      SARS-CoV, as well as a SARS-CoV pseudovirus packaged in the SARS-CoV envelope.
      The SARS-CoV entered caveolin-1-negative HepG2 cells, and the entry was
      significantly inhibited by treatment with chlorpromazine, an inhibitor for
      clathrin-dependent endocytosis, and by small interfering RNA-mediated gene
      silencing for the clathrin heavy chain. Furthermore, the SARS-CoV entered COS7
      cells transfected with the mutant of ACE2 with the cytoplasmic tail deleted, SARS
      CoV receptor, as well as the wild-type ACE2, and their entries were significantly
      inhibited by treatment with chlorpromazine. In addition, ACE2 translocated into
      EEA1-positive early endosomes immediately after the virus attachment to ACE2.
      These results suggest that when SARS-CoV binds ACE2 it is internalized and
      penetrates early endosomes in a clathrin-dependent manner and that the
      cytoplasmic tail of ACE2 is not required for the penetration of SARS-CoV.

PMID- 17522232
TI  - Vif counteracts a cyclophilin A-imposed inhibition of simian immunodeficiency
      viruses in human cells.
AB  - Vif is a primate lentiviral accessory protein that is crucial for viral
      infectivity. Vif counteracts the antiviral activity of host deaminases such as
      APOBEC3G and APOBEC3F. We now report a novel function of African green monkey
      simian immunodeficiency virus (SIVagm) Vif that promotes replication of SIVagm in
      human cells lacking detectable deaminase activity. We found that cyclophilin A
      (CypA) was excluded from wild-type SIV particles but was efficiently packaged
      into vif-deficient SIVagm virions. The presence of CypA in vif-defective SIVagm
      was correlated with reduced viral replication. Infection of CypA knockout Jurkat
      cells or treatment of Jurkat cells with cyclosporine A eliminated the Vif
      sensitive inhibition and resulted in replication profiles that were similar for
      wild-type and vif-deficient SIVagm. Importantly, the inhibitory effect of CypA
      was restricted to virus-producing cells and was TRIM5alpha independent. The
      abilities of SIVagm Vif to inhibit encapsidation of CypA and to increase viral
      infectivity were shared by rhesus macaque SIV Vif and thus seem to be general
      properties of SIV Vif proteins. Exclusion of CypA from SIVagm particles was not
      associated with intracellular degradation, suggesting a mode of Vif action
      distinct from that proposed for APOBEC3G. This is the first report of a novel vif
      sensitive antiviral activity of human CypA that may limit zoonotic transmission
      of SIV and the first demonstration of CypA encapsidation into a virus other than
      human immunodeficiency virus type 1.

PMID- 17522233
TI  - Identification of nonessential regions of the nsp2 replicase protein of porcine
      reproductive and respiratory syndrome virus strain VR-2332 for replication in
      cell culture.
AB  - The nonstructural protein 2 (nsp2) of porcine reproductive and respiratory
      syndrome virus (PRRSV) is a multidomain protein and has been shown to undergo
      remarkable genetic variation, primarily in its middle region, while exhibiting
      high conservation in the N-terminal putative protease domain and the C-terminal
      predicted transmembrane region. A reverse genetics system of PRRSV North American
      prototype VR-2332 was developed to explore the importance of different regions of
      nsp2 for viral replication. A series of mutants with in-frame deletions in the
      nsp2 coding region were engineered, and infectious viruses were subsequently
      recovered from transfected cells and further characterized. The results
      demonstrated that the cysteine protease domain (PL2), the PL2 downstream flanking
      sequence (amino acids [aa] 181 to 323), and the putative transmembrane domain
      were critical for replication. In contrast, the segment of nsp2 preceding the PL2
      domain (aa 13 to 35) was dispensable for viral replication, and the nsp2 middle
      hypervariable region (aa 324 to 813) tolerated 100-aa or 200-aa deletions but
      could not be removed as a whole; the largest deletion was about 400 aa
      (nsp2Delta324-726). Characterization of the mutants demonstrated that those with
      small deletions possessed growth kinetics and RNA expression profiles similar to
      those of the parental virus, while the nsp2Delta324-726 mutant displayed
      decreased cytolytic activity on MARC-145 cells and did not develop visible
      plaques. Finally, the utilization of the genetic flexibility of nsp2 to express
      foreign genes was examined by inserting the gene encoding green fluorescent
      protein (GFP) in frame into one nsp2 deletion mutant construct. The recombinant
      virus was viable but impaired and unstable and gradually gained parental growth
      kinetics by the loss of most of the GFP gene.

PMID- 17522234
TI  - Induction of serum IL-18 with Propionibacterium acnes and lipopolysaccharide in
      phagocytic macrophage-inactivated mice.
AB  - IL-18, an important regulator of immune responses, is expressed in activated
      macrophages and also in nonimmune cells, such as keratinocytes and epithelial
      cells. Increased levels of serum IL-18 are reported in patients with a wide
      variety of diseases, but it is unclear which type of cell is the major source of
      serum IL-18. Here, we showed that the administration of liposomes encapsulating
      clodronate (Clo-lip) in mice selectively depleted F4/80(+) phagocytic macrophages
      in the liver and spleen. Serum levels of mature IL-18 with 18 kDa were increased
      markedly in mice treated with Propionibacterium acnes and LPS, whereas
      administration of Clo-lip and gadolinium chloride, another widely used macrophage
      inactivator, showed no obvious effect on serum IL-18 levels, which were marginal
      in the liver, lung, and spleen and more pronounced in the intestines, especially
      in the duodenum. Treatment with P. acnes alone induced IL-18 more than twofold in
      each organ, and P. acnes and LPS induced a marked increase in IL-18 levels in the
      liver and spleen but decreased in the intestines. The administration of Clo-lip
      showed only a marginal effect on the IL-18 levels in these organs. Furthermore,
      serum levels of liver enzymes and TNF-alpha and liver injury (necrotic change and
      granuloma formation) induced by P. acnes and LPS were reduced moderately by Clo
      lip. These results suggest that phagocytic macrophages do not actively contribute
      to the induction of serum IL-18 and liver injury in mice treated with P. acnes
      and LPS.

PMID- 17522235
TI  - An interpretation of the EBCTCG data.
AB  - Published data and figures from the Early Breast Cancer Clinical Trialists'
      Collaborative Group are explored and interpreted as supporting a concept that the
      prime impact of adjuvant hormonal and polychemotherapy therapy is on soon-to
      emerge tumors, with the timing of benefit accrual being mostly limited to the
      time of drug administration. Nevertheless, once benefit in reducing recurrence
      occurs, the benefit is maintained for years. Depending on how this is viewed,
      there may or may not be a carryover effect of these therapies in the setting of
      adjuvant breast cancer.

PMID- 17522236
TI  - Commentary: the hazards of survival comparisons.

PMID- 17522237
TI  - Sentinel lymph node biopsy in male patients with early breast cancer.
AB  - Mastectomy with axillary dissection is still the most commonly recommended
      procedure for male breast cancer. The aim of this study was to retrospectively
      evaluate our experience in 32 male patients with early breast cancer who
      underwent sentinel lymph node biopsy (SLNB) and axillary dissection only in cases
      of metastases in the sentinel lymph node (SLN). The median age was 58 years
      (range, 33-80). Lymphoscintigraphy was successful in all patients, with a mean
      number of visualized SLNs per patient of 1.3 (range, 1-2). At surgery, the
      identification rate of the SLN was 100%, with a mean number of removed SLNs per
      patient of 1.5 (range, 1-3). Twenty-six patients had negative SLNs, six patients
      had positive SLNs. Two patients with metastatic SLNs had additional positive
      nodes. After a median follow-up of 30 months (range, 1-63) no axillary
      reappearance of the disease occurred. As with women, we recommend SLNB in male
      patients with breast cancer and clinically negative axilla.

PMID- 17522238
TI  - The molecular perspective: hepatitis B virus.

PMID- 17522239
TI  - Nonbacterial thrombotic endocarditis in cancer patients: pathogenesis, diagnosis,
      and treatment.
AB  - Thrombophilia is a well-described consequence of cancer and its treatment. The
      pathogenesis of this phenomenon is complex and multifactorial. Nonbacterial
      thrombotic endocarditis (NBTE) is a serious and potentially underdiagnosed
      manifestation of this prothrombotic state that can cause substantial morbidity in
      affected patients, most notably recurrent or multiple ischemic cerebrovascular
      strokes. Diagnosis of NBTE requires a high degree of clinical suspicion as well
      as the judicious use of two-dimensional echocardiography to document the presence
      of valvular thrombi. In the absence of contraindications to therapy, treatment
      consists of systemic anticoagulation, which may ameliorate symptoms and prevent
      further thromboembolic episodes, as well as control of the underlying malignancy
      whenever possible.

PMID- 17522240
TI  - Anal cancer: an overview.
AB  - Anal cancer is a rare tumor with an incidence that has been rising over the last
      25 years. The disease was once thought to develop as a result of chronic
      irritation, but it is now known that this is not the case. Multiple risk factors,
      including human papillomavirus (HPV) infection, anoreceptive intercourse,
      cigarette smoking, and immunosuppression, have been identified. HIV infection is
      also associated with anal cancer; there is a higher incidence in HIV-positive
      patients but the direct relationship between HIV and anal cancer has been
      difficult to separate from the prevalence of HPV in this population. HIV
      infection is also associated with anal cancer; there are increasing numbers of
      HIV-positive patients being diagnosed with the disease. Treatment of anal cancer
      prior to the 1970s involved abdominoperineal resection, but the standard of care
      is now concurrent chemoradiation therapy, with surgery reserved for those
      patients with residual disease. We present a case of anal cancer followed by a
      general discussion of both risk factors and treatment.

PMID- 17522241
TI  - Tumor suppressor role of Notch-1 signaling in neuroendocrine tumors.
AB  - A growing body of literature is demonstrating that Notch signaling is a more
      complex process than originally thought. Contradictory findings of notch-1 acting
      as an oncogene or a tumor suppressor revealed that its role is very specific to
      the cellular context. In this review we focus on the tumor suppressor role of
      Notch-1 signaling in neuroendocrine tumors (NETs) such as carcinoid and medullary
      thyroid cancers. NETs secrete various bioactive hormones that can cause
      debilitating symptoms. Surgery is the only potential curative treatment for the
      patients with NETs. Notch-1 signaling is absent in these tumors and activation of
      Notch-1 significantly reduces tumor growth in vitro. Therefore, identification of
      compound(s) that activate the Notch-1 pathway in NETs could be a potential
      strategy to treat patients with NETs.

PMID- 17522242
TI  - Multi-institutional phase II study of S-1 monotherapy in advanced gastric cancer
      with pharmacokinetic and pharmacogenomic evaluations.
AB  - This study describes the first phase II study of S-1, a novel oral
      fluoropyrimidine, in a non-Japanese Asian population with advanced gastric
      cancer. S-1 was administered twice daily for 28 days every 6 weeks. A
      pharmacokinetic study was performed on day 28 of cycles 1 and 3. Genomic DNA from
      peripheral mononuclear cells was analyzed using a cDNA microarray-based
      comparative genomic hybridization (CGH) method. Thirty-one patients were
      initially given a dose of 35 mg/m(2) twice daily (bid) (group 1); then, the
      protocol was amended by increasing the dose to 40 mg/m(2) bid for an additional
      31 patients (group 2) because of good tolerability to S-1. The overall response
      rate was 19.3% (95% confidence interval, 9.2%-29.5%). Over a median follow-up
      duration of 265 days, the median time to progression and overall survival time
      were 126 and 264 days, respectively. The 1-year survival rate was 34%. There was
      no grade 4 toxicity and the major adverse event was anemia. Pharmacokinetic
      parameters were similar to those of the previous Japanese reports. Microarray CGH
      identified 18 genes with copy number changes that were associated with hemoglobin
      reduction with S-1 treatment. A logistic regression analysis, integrating one
      clinical parameter (initial hemoglobin level) combined with three genetic copy
      number variations (HIST1H2BL, C10orf127, and XPNPEP2), provided a predictive
      model for the development of severe hemoglobin reduction. In conclusion, this
      study showed the feasibility of using S-1 at 35 mg/m(2) bid in gastric cancer. We
      suggest that the pharmacogenomic markers identified in this study may be
      potential candidates for predicting anemia after S-1 treatment.

PMID- 17522243
TI  - Intensity-modulated radiation therapy for head and neck carcinoma.
AB  - Intensity-modulated radiation therapy (IMRT) for head and neck tumors refers to a
      new approach that aims at increasing the radiation dose gradient between the
      target tissues and the surrounding normal tissues at risk, thus offering the
      prospect of increasing the locoregional control probability while decreasing the
      complication rate. As a prerequisite, IMRT requires a proper selection and
      delineation of target volumes. For the latter, recent data indicate the potential
      of functional imaging to complement anatomic imaging modalities. Nonrandomized
      clinical series in paranasal sinuses and pharyngolaryngeal carcinoma have shown
      that IMRT was able to achieve a very high rate of locoregional control with less
      morbidity, such as dry-eye syndrome, xerostomia, and swallowing dysfunction. The
      promising results of IMRT are likely to be achieved when many treatment
      conditions are met, for example, optimal selection and delineation of the target
      volumes and organs at risk, appropriate physical quality control of the
      irradiation, and accurate patient setup with the use of onboard imaging. Because
      of the complexity of the various tasks, it is thus likely that these conditions
      will only be met in institutions having large patient throughput and experience
      with IMRT. Therefore, patient referral to those institutions is recommended.

PMID- 17522244
TI  - Commentary: IMRT for head and neck cancer: many chapters left to write.

PMID- 17522245
TI  - Primary effusion lymphoma.
AB  - Primary effusion lymphoma (PEL) is a rare HIV-associated non-Hodgkin's lymphoma
      (NHL) that accounts for approximately 4% of all HIV-associated NHL. PEL has a
      unique clinical presentation in having a predilection for arising in body
      cavities such as the pleural space, pericardium, and peritoneum. PEL cells are
      morphologically variable with a null lymphocyte immunophenotype and evidence of
      human herpesvirus (HHV)-8 infection. The exact oncogenic mechanisms of HHV-8 have
      not been clearly defined. Treatment is usually with combination CHOP
      (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and
      antiretroviral therapy (if HIV positive). The prognosis for PEL is poor, with a
      median survival time of around 6 months. As the exact molecular steps in HHV-8
      driven oncogenesis are unraveled, it is hoped that more specific therapeutic
      targets will be revealed.

PMID- 17522246
TI  - FDA drug approval summary: panitumumab (Vectibix).
AB  - On September 27, 2006, the U.S. Food and Drug Administration granted approval to
      panitumumab (Vectibix, Amgen, Inc., Thousand Oaks, CA) for the treatment of
      patients with epidermal growth factor receptor (EGFR)-expressing, metastatic
      colorectal carcinoma with disease progression on or following fluoropyrimidine-,
      oxaliplatin-, and irinotecan-containing chemotherapy regimens. Panitumumab
      approval is based on the results of a single, open-label, randomized,
      multinational study that enrolled 463 patients with EGFR-expressing (at least 1+
      membrane staining in > or =1% of tumor cells) metastatic colorectal cancer.
      Patients were randomized to either best supportive care (BSC) alone or BSC plus
      panitumumab, 6 mg/kg i.v., every other week. The primary study endpoint was
      progression-free survival (PFS), determined by an independent review committee
      that was blinded as to treatment assignment. BSC patients who progressed were
      eligible to receive panitumumab. The study patients' median age was 62 years,
      with 40% aged > or =65; 63% were male, 99% were white, 86% had a baseline Eastern
      Cooperative Oncology Group performance status score of 0 or 1, and 67% had colon
      cancer. The median time from diagnosis of metastases was approximately 19 months
      and the median number of prior therapies was 2.4. The PFS duration was
      significantly longer among patients randomized to receive panitumumab in addition
      to BSC (n = 231) compared with BSC alone (n = 232). The median and mean PFS times
      were 56 and 96.4 days, respectively, for patients receiving panitumumab and 51
      and 59.7 days, respectively, for patients receiving BSC alone. Nineteen partial
      responses (8%, 95% confidence interval [CI], 5.3%-12.5%) were observed in
      panitumumab treated patients. The median duration of response was 17 weeks (95%
      CI, 16-25 weeks). Approximately 75% of patients in the BSC alone arm crossed over
      to receive panitumumab after disease progression. There was no difference in
      overall survival between the two study arms. The most common adverse events were
      skin rash, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and
      diarrhea. The most serious adverse events were pulmonary fibrosis, severe
      dermatologic toxicity complicated by infectious sequelae and septic death,
      infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, diarrhea,
      and constipation.

PMID- 17522247
TI  - The effectiveness of darbepoetin alfa administered every 3 weeks on hematologic
      outcomes and quality of life in older patients with chemotherapy-induced anemia.
AB  - Chemotherapy-induced anemia (CIA) may substantially impact the health-related
      quality of life (HRQoL) of older cancer patients. This exploratory analysis
      evaluated the effect of darbepoetin alfa administered as a fixed dose (300
      microg) every 3 weeks (Q3W) on hematologic outcomes, HRQoL, and safety in older
      (> or =65 years old) versus younger (<65 years old) patients with CIA (hemoglobin
      <11 g/dl). Patients were categorized by age at screening: <65, > or =65 to <70, >
      or =70 to <75, > or =75 to <80, and > or =80 years old. Patients who received at
      least one dose of darbepoetin alfa were included in the analysis; of 1,493
      patients, 724 were > or =65 years old. Age did not appear to influence
      hematologic outcomes after treatment with darbepoetin alfa; in all age
      categories, similar percentages of patients (78%-80%) achieved the target
      hemoglobin in approximately the same time (4-5 weeks). Also, the percentage of
      patients in each age category who received RBC transfusions was reduced from 10%
      13% in month 1 to 2%-4% in month 4. Although younger patients reported the
      greatest improvement in HRQoL scores, approximately one half in each older age
      category reported clinically significant improvement in fatigue, and improvement
      in the Energy and Overall Health Assessment and Work Productivity and Activity
      Impairment scales. There were no treatment-related deaths. Treatment-related
      thromboembolic events were reported by <1% of patients <65 years old and <1% of
      patients > or =65 to <70 and > or =70 to <75 years old. Darbepoetin alfa Q3W
      appeared well tolerated and effective for treating older patients with CIA.

PMID- 17522248
TI  - Effect on body weight and safety of RC-1291, a novel, orally available ghrelin
      mimetic and growth hormone secretagogue: results of a phase I, randomized,
      placebo-controlled, multiple-dose study in healthy volunteers.
AB  - PURPOSE: RC-1291 is a novel, oral ghrelin mimetic and growth hormone (GH)
      secretagogue being developed to increase appetite and lean muscle mass in
      patients with cancer-associated anorexia/cachexia. This randomized, double-blind,
      placebo-controlled, multiple-dose, dose-escalation phase I study in healthy
      volunteers evaluated RC-1291 once daily (qd) and twice daily (bid) for effect on
      body weight and safety. METHODS: The study was conducted with three sequential
      groups of volunteers. Panel A subjects (n = 8) received placebo or RC-1291, 25 mg
      qd, for 5 days. Panel B subjects received RC-1291, 25 mg bid or 50 mg qd, for 6
      days then crossed over to the other dosage for 5 days (n = 12); three subjects
      received placebo for all 11 doses to maintain double-blinding. Panel C subjects
      (n = 9) received placebo or RC-1291, 75 mg qd, for 6 days. RESULTS: Subjects who
      received RC-1291, 50 or 75 mg, had significant dose-related weight gain after 6
      days versus placebo, with the greatest increases seen with daily dosing. The mean
      increase in weight from baseline after 50 mg qd was 1.25 +/- 0.725 kg (p = .0022
      versus placebo), and after 75 mg qd it was 1.16 +/- 0.651 kg (p = .0022 versus
      placebo). One subject in the 50 mg qd group had moderate transient elevation in
      aspartate aminotransferase and alanine aminotransferase levels. No other
      laboratory or clinical adverse events of consequence were reported. CONCLUSIONS:
      Results indicate that RC-1291 produces dose-related increases in body weight with
      no dose-limiting adverse effects, and may be an effective treatment for
      anorexia/cachexia.

PMID- 17522249
TI  - Management and preparedness for infusion and hypersensitivity reactions.
AB  - BACKGROUND: Like nearly all systemic cancer therapies, monoclonal antibodies are
      associated with hypersensitivity reactions. This article reviews the
      characteristics and management of hypersensitivity reactions to monoclonal
      antibodies and commonly used chemotherapy agents. METHODS: MEDLINE was searched
      for recent studies and reviews pertaining to hypersensitivity reactions with
      monoclonal antibodies (cetuximab, rituximab, trastuzumab, panitumumab,
      bevacizumab), platinum compounds (carboplatin, oxaliplatin), and taxanes
      (paclitaxel, docetaxel). Emphasis was placed on articles that provided practical
      information on hypersensitivity reaction management. Data found in the literature
      were supplemented with information from the package insert for each agent.
      RESULTS: Severe hypersensitivity reactions are rare, with an incidence of < or
      =5%, provided patients receive proper premedication, close monitoring, and prompt
      intervention when symptoms occur. Hypersensitivity reactions to platinum
      compounds are generally consistent with type 1 hypersensitivity, occurring after
      multiple cycles of therapy. Reactions to taxanes and monoclonal antibodies
      produce similar symptoms, but are generally immediate, occurring during the first
      few minutes of the first or second infusion. However, 10%-30% of reactions to
      monoclonal antibodies are delayed, and may occur in later infusions, indicating
      the importance of close observation of the patient following administration. Mild
      to-moderate reactions can be managed by temporary infusion interruption,
      reduction of the infusion rate, and symptom management. Rechallenge should be
      considered after complete resolution of all symptoms. Severe reactions may
      require treatment discontinuation. CONCLUSION: Hypersensitivity or infusion
      reactions to platinum compounds are acquired; reactions to taxanes and monoclonal
      antibodies are immediate and typically occur during the first few minutes of the
      first infusion. The different time of onset should be considered when developing
      strategies for preventing and managing hypersensitivity reactions. The decision
      to rechallenge or discontinue treatment after a reaction occurs depends on the
      severity of the reaction and other clinical factors.

PMID- 17522250
TI  - Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an
      evolving paradigm in clinical management.
AB  - Epidermal growth factor receptor inhibitors (EGFRIs) have demonstrated improved
      overall survival in patients with non-small cell lung cancer, pancreatic cancer,
      and colorectal cancer; however, their use is associated with dermatologic
      reactions of varying severity. The similar spectrum of events observed with
      monoclonal antibodies and tyrosine kinase inhibitors suggests such toxicities are
      a class effect. While such reactions do not necessarily require any alteration in
      EGFRI treatment, being best addressed through symptomatic treatment, there is
      limited evidence on which to base such therapies. In October 2006, at an
      international and interdisciplinary EGFRI dermatologic toxicity forum, the
      underlying mechanisms of these toxicities were discussed and commonly used
      therapeutic interventions were evaluated. Our aim was to reach a current
      consensus on management strategies. A three-tiered, EGFRI-focused toxicity
      grading system is suggested for the purposes of therapeutic decision making, and
      as a framework on which to build a stepwise approach to intervention. This
      approach to successful management is specifically tailored to accurately
      categorize dermatologic toxicity associated with EGFRIs, and can be easily
      applied by all health care professionals. The goal is to maximize quality of life
      in patients who are being treated with these agents--many of whom will be on
      these drugs for several months or even years.

PMID- 17522251
TI  - Location rather than CD62L phenotype is critical in the early establishment of
      influenza-specific CD8+ T cell memory.
AB  - The rapid recall of influenza virus-specific CD8(+) T cell effector function is
      protective, although our understanding of T cell memory remains incomplete.
      Recent debate has focused particularly on the CD62L lymph node homing receptor.
      The present analysis shows that although functional memory can be established
      from both CD62L(hi) and CD62L(lo) CD8(+) T cell subsets soon after initial
      encounter between naive precursors and antigen, the optimal precursors are
      CD8(+)CD44(hi)CD25(lo) immune lymphocytes isolated from draining lymph nodes on
      day 3.5 after influenza virus infection. Analysis of primed T cells at different
      times after challenge indicates that the capacity to transfer memory is
      diminished at the peak of the primary cytotoxic T lymphocyte response,
      challenging speculations that the transition to memory first requires full
      differentiation to effector status. It seems that location rather than CD62Lhi/lo
      phenotype may be the more profitable focus for further dissection of the early
      establishment of T cell memory.

PMID- 17522252
TI  - Mother-offspring competition promotes colonization success.
AB  - Colonization is the crucial process underlying range expansions, biological
      invasions, and metapopulation dynamics. Which individuals leave their natal
      population to colonize empty habitats is a crucial question and is presently
      unresolved. Dispersal is the first step in colonization. However, not all
      dispersing individuals are necessarily good colonizers. Indeed, in some species,
      the phenotype of dispersers differs depending on the selective pressures that
      induce dispersal. In particular, kin-based interactions, a factor driving social
      evolution, should induce different social response profiles in nondispersing and
      dispersing individuals. Kin competition (defined here as between the mother and
      offspring) has been proven to produce dispersers with a particular phenotype that
      may enhance their colonizing ability. By using the common lizard (Lacerta
      vivipara), we conducted a multipopulation experiment to study the effect of kin
      competition on dispersal and colonization success. We manipulated mother
      offspring interactions, which are the most important component of kin competition
      in the studied species, at the family and population levels and measured the
      consequences on colonization success. We demonstrate that mother-offspring
      competition at the population level significantly influences colonization
      success. Increased competition at the population level enhanced the colonization
      rate of the largest juveniles as well as the growth and survival of the
      colonizers. Based on these results, we calculated that kin-induced colonization
      halves the extinction probability of a newly initiated population. Because
      interactions between relatives are likely to affect the ability of a species to
      track habitat modifications, kin-based dispersal should be considered in the
      study of invasion dynamics and metapopulation functioning.

PMID- 17522253
TI  - A1 adenosine receptors play an essential role in protecting the embryo against
      hypoxia.
AB  - Embryos can be exposed to environmental factors that induce hypoxia. Currently,
      our understanding of the effects of hypoxia on early mammalian development is
      modest. Potential mediators of hypoxia action include the nucleoside adenosine,
      which acts through A(1) adenosine receptors (A(1)ARs) and mediates adverse
      effects of hypoxia on the neonatal brain. We hypothesized that A(1)ARs may also
      play a role in mediating effects of hypoxia on the embryo. When pregnant dams
      were exposed to hypoxia (10% O(2)) beginning at embryonic day (E) 7.5 or 8.5 and
      continued for 24-96 h, A(1)AR+/+ embryos manifested growth inhibition and a
      disproportionate reduction in heart size, including thinner ventricular walls.
      Yet, when dams were exposed to hypoxia, embryos lacking A(1)ARs (A(1)AR-/-) had
      much more severe growth retardation than A(1)AR+/+ or +/- embryos. When levels of
      hypoxia-inducible factor 1alpha (HIF1alpha) were examined, A(1)AR-/- embryos had
      less stabilized HIF1alpha protein than A(1)AR+/- littermates. Normal patterns of
      cardiac gene expression were also disturbed in A(1)AR-/- embryos exposed to
      hypoxia. These results show that short periods of hypoxia during early
      embryogenesis can result in intrauterine growth retardation. We identify
      adenosine and A(1)ARs as playing an essential role in protecting the embryo from
      hypoxia.

PMID- 17522254
TI  - Up-regulation of heat shock proteins is essential for cold survival during insect
      diapause.
AB  - Diapause, the dormancy common to overwintering insects, evokes a unique pattern
      of gene expression. In the flesh fly, most, but not all, of the fly's heat shock
      proteins (Hsps) are up-regulated. The diapause up-regulated Hsps include two
      members of the Hsp70 family, one member of the Hsp60 family (TCP-1), at least
      four members of the small Hsp family, and a small Hsp pseudogene. Expression of
      an Hsp70 cognate, Hsc70, is uninfluenced by diapause, and Hsp90 is actually down
      regulated during diapause, thus diapause differs from common stress responses
      that elicit synchronous up-regulation of all Hsps. Up-regulation of the Hsps
      begins at the onset of diapause, persists throughout the overwintering period,
      and ceases within hours after the fly receives the signal to reinitiate
      development. The up-regulation of Hsps appears to be common to diapause in
      species representing diverse insect orders including Diptera, Lepidoptera,
      Coleoptera, and Hymenoptera as well as in diapauses that occur in different
      developmental stages (embryo, larva, pupa, adult). Suppressing expression of
      Hsp23 and Hsp70 in flies by using RNAi did not alter the decision to enter
      diapause or the duration of diapause, but it had a profound effect on the pupa's
      ability to survive low temperatures. We thus propose that up-regulation of Hsps
      during diapause is a major factor contributing to cold-hardiness of overwintering
      insects.

PMID- 17522255
TI  - Estrogen receptor beta-deficient female mice develop a bladder phenotype
      resembling human interstitial cystitis.
AB  - Interstitial cystitis/painful bladder syndrome is a disease seen mostly in women,
      and symptoms tend to be worse premenopausally or during ovulation. The four
      cardinal symptoms of interstitial cystitis/painful bladder syndrome are bladder
      pain, urgency, frequency, and nocturia. Estrogen has been implicated in the
      etiology of this disease, but the role of the two estrogen receptors (ER),
      ERalpha and ERbeta, has not been investigated. We found that, in the bladders of
      WT mice, ERbeta is expressed in the basal cell layer of the urothelium. Bladders
      of male ERbeta(-/-) mice were intact and morphologically indistinguishable from
      those of their WT littermates. However, in female ERbeta(-/-) mice, there was
      ulceration and atrophy of bladder urothelium concomitant with infiltration of
      gammadelta T cells concentrated in the areas of atrophy and shedding of
      urothelium. The data support the idea that activated gammadelta T cells are
      causing the damage to the urothelium. The hyperactivity of T cells may be because
      of an imbalance between ERalpha and ERbeta signaling in female ERbeta(-/-) mice.
      Our data suggest that reduced ERbeta signaling might have a role in the
      pathogenesis of interstitial cystitis, and ERbeta could be a candidate for a
      target of medical therapy.

PMID- 17522256
TI  - Fc receptor-like 5 inhibits B cell activation via SHP-1 tyrosine phosphatase
      recruitment.
AB  - The Fc receptor-like protein 5 (FCRL5) on B cells has both an immunoreceptor
      tyrosine-based activation motif (ITAM)-like sequence and two consensus
      immunoreceptor tyrosine-based inhibitory motifs (ITIM) in its cytoplasmic region.
      To evaluate its signaling potential, we expressed constructs for chimeric
      molecules composed of the cytoplasmic region of FCRL5 and the extracellular and
      transmembrane regions of the IgG Fc receptor FcgammaRIIB in a B cell line lacking
      an endogenous Fc receptor. Coligation of this fusion protein with the B cell
      receptor (BCR) inhibited BCR-mediated calcium mobilization, intracellular
      tyrosine phosphorylation, and Erk kinase activation. Our mutational analysis
      indicated that, whereas tyrosines in both the inhibitory and activation motifs
      are phosphorylated after ligation, only those in ITIMs influence BCR-mediated
      signaling. This FCRL5 inhibitory effect was mediated through dual ITIM
      recruitment of the SH2-containing protein tyrosine phosphatase, SHP-1, which in
      turn dephosphorylates the ITAM-based tyrosines in BCR Igalpha/Igbeta
      heterodimers. An FCRL5 inhibitory effect on BCR signaling was likewise
      demonstrable for primary B cells. Although its ligand is presently unknown, we
      conclude that FCRL5 has the functional potential to serve as an inhibitory
      coreceptor on mature B cells in humans.

PMID- 17522257
TI  - Geometry-induced asymmetric diffusion.
AB  - Past work has shown that ions can pass through a membrane more readily in one
      direction than the other. We demonstrate here in a model and an experiment that
      for a mixture of small and large particles such asymmetric diffusion can arise
      solely from an asymmetry in the geometry of the pores of the membrane. Our
      deterministic simulation considers a two-dimensional gas of elastic disks of two
      sizes diffusing through a membrane, and our laboratory experiment examines the
      diffusion of glass beads of two sizes through a metal membrane. In both
      experiment and simulation, the membrane is permeable only to the smaller
      particles, and the asymmetric pores lead to an asymmetry in the diffusion rates
      of these particles. The presence of even a small percentage of large particles
      can clog a membrane, preventing passage of the small particles in one direction
      while permitting free flow of the small particles in the other direction. The
      purely geometric kinetic constraints may play a role in common biological
      contexts such as membrane ion channels.

PMID- 17522258
TI  - Biphasic role for Wnt/beta-catenin signaling in cardiac specification in
      zebrafish and embryonic stem cells.
AB  - Understanding pathways controlling cardiac development may offer insights that
      are useful for stem cell-based cardiac repair. Developmental studies indicate
      that the Wnt/beta-catenin pathway negatively regulates cardiac differentiation,
      whereas studies with pluripotent embryonal carcinoma cells suggest that this
      pathway promotes cardiogenesis. This apparent contradiction led us to hypothesize
      that Wnt/beta-catenin signaling acts biphasically, either promoting or inhibiting
      cardiogenesis depending on timing. We used inducible promoters to activate or
      repress Wnt/beta-catenin signaling in zebrafish embryos at different times of
      development. We found that Wnt/beta-catenin signaling before gastrulation
      promotes cardiac differentiation, whereas signaling during gastrulation inhibits
      heart formation. Early treatment of differentiating mouse embryonic stem (ES)
      cells with Wnt-3A stimulates mesoderm induction, activates a feedback loop that
      subsequently represses the Wnt pathway, and increases cardiac differentiation.
      Conversely, late activation of beta-catenin signaling reduces cardiac
      differentiation in ES cells. Finally, constitutive overexpression of the beta
      catenin-independent ligand Wnt-11 increases cardiogenesis in differentiating
      mouse ES cells. Thus, Wnt/beta-catenin signaling promotes cardiac differentiation
      at early developmental stages and inhibits it later. Control of this pathway may
      promote derivation of cardiomyocytes for basic research and cell therapy
      applications.

PMID- 17522259
TI  - Polyelectrostatic interactions of disordered ligands suggest a physical basis for
      ultrasensitivity.
AB  - Regulation of biological processes often involves phosphorylation of
      intrinsically disordered protein regions, thereby modulating protein
      interactions. Initiation of DNA replication in yeast requires elimination of the
      cyclin-dependent kinase inhibitor Sic1 via the SCF(Cdc4) ubiquitin ligase.
      Intriguingly, the substrate adapter subunit Cdc4 binds to Sic1 only after
      phosphorylation of a minimum of any six of the nine cyclin-dependent kinase sites
      on Sic1. To investigate the physical basis of this ultrasensitive interaction, we
      consider a mean-field statistical mechanical model for the electrostatic
      interactions between a single receptor site and a conformationally disordered
      polyvalent ligand. The formulation treats phosphorylation sites as negative
      contributions to the total charge of the ligand and addresses its interplay with
      the strength of the favorable ligand-receptor contact. Our model predicts a
      threshold number of phosphorylation sites for receptor-ligand binding, suggesting
      that ultrasensitivity in the Sic1-Cdc4 system may be driven at least in part by
      cumulative electrostatic interactions. This hypothesis is supported by
      experimental affinities of Cdc4 for Sic1 fragments with different total charges.
      Thus, polyelectrostatic interactions may provide a simple yet powerful framework
      for understanding the modulation of protein interactions by multiple
      phosphorylation sites in disordered protein regions.

PMID- 17522260
TI  - Quantifying HIV-1 transmission due to contaminated injections.
AB  - Assessments of the importance of different routes of HIV-1 (HIV) transmission are
      vital for prioritization of control efforts. Lack of consistent direct data and
      large uncertainty in the risk of HIV transmission from HIV-contaminated
      injections has made quantifying the proportion of transmission caused by
      contaminated injections in sub-Saharan Africa difficult and unavoidably
      subjective. Depending on the risk assumed, estimates have ranged from 2.5% to 30%
      or more. We present a method based on an age-structured transmission model that
      allows the relative contribution of HIV-contaminated injections, and other routes
      of HIV transmission, to be robustly estimated, both fully quantifying and
      substantially reducing the associated uncertainty. To do this, we adopt a
      Bayesian perspective, and show how prior beliefs regarding the safety of
      injections and the proportion of HIV incidence due to contaminated injections
      should, in many cases, be substantially modified in light of age-stratified
      incidence and injection data, resulting in improved (posterior) estimates.
      Applying the method to data from rural southwest Uganda, we show that the highest
      estimates of the proportion of incidence due to injections are reduced from 15.5%
      (95% credible interval) (0.7%, 44.9%) to 5.2% (0.5%, 17.0%) if random mixing is
      assumed, and from 14.6% (0.7%, 42.5%) to 11.8% (1.2%, 32.5%) under assortative
      mixing. Lower, and more widely accepted, estimates remain largely unchanged,
      between 1% and 3% (0.1-6.3%). Although important uncertainty remains, our
      analysis shows that in rural Uganda, contaminated injections are unlikely to
      account for a large proportion of HIV incidence. This result is likely to be
      generalizable to many other populations in sub-Saharan Africa.

PMID- 17522261
TI  - Dynamic course of intracortical TMS paired-pulse responses during recovery of
      motor function after stroke.
AB  - BACKGROUND: Recovery of motor function after stroke may be associated with
      changes in inhibitory and facilitatory circuits within the motor cortex.
      OBJECTIVE: We explored such changes longitudinally after stroke, using
      transcranial magnetic stimulation (TMS). METHODS: Subjects (N = 27) with a single
      cerebral infarction affecting movement of either hand were studied at <10 days
      poststroke, 1 month, and 6 months. Age-matched control subjects (N = 9) were
      studied at 2 times. RESULTS: In contrast to previous studies, paired-pulse
      inhibition was increased in patients with a subcortical stroke compared to
      control subjects. After a cortical stroke, paired-pulse facilitation was also
      increased. Stroke location affected the time course of inhibition. Subcortical
      stroke resulted in increased inhibition initially that decreased over time,
      whereas cortical stroke had no significant effect on inhibition and a more
      immediate and lasting effect on facilitation. CONCLUSIONS: The time course of a
      decline in inhibition based on TMS after subcortical stroke followed the gain in
      motor recovery. Increased facilitation in cortical stroke patients is more likely
      to represent the effect of early cortical circuit disruption and may not play a
      role in subacute changes in motor function.

PMID- 17522262
TI  - Evidence for gut factor in K+ homeostasis.
AB  - We tested the hypothesis that K(+) intake is sensed by putative K(+) sensors in
      the splanchnic areas, and renal K(+) handling is regulated by this signal. K(+)
      was infused for 2 h into overnight-fasted rats via the jugular vein (systemic
      infusion), hepatic portal vein (intraportal infusion), or stomach (intragastric
      infusion) (n = 5 each), and plasma K(+) concentration ([K(+)]) and renal K(+)
      excretion were measured during the 2-h preinfusion, 2-h K(+) infusion, and 3-h
      washout periods. During systemic K(+) infusion, plasma [K(+)] increased by
      approximately 1.3 mM (P < 0.05), and, on cessation of the K(+) infusion, plasma
      [K(+)] fell to the preinfusion level within 1-2 h. Renal K(+) excretion changed
      in proportion to the changes in plasma [K(+)]. During intraportal or intragastric
      K(+) infusion, plasma [K(+)] and renal K(+) excretion profiles were similar to
      those with systemic infusion. The effects of K(+) infusions via the different
      routes (n = 5 or 6 each) were also studied during simultaneous feeding of
      overnight-fasted rats with a K(+)-deficient diet. During the meal, intraportal
      infusion resulted in increases in plasma [K(+)] similar to those with the
      systemic K(+) infusion, while intragastric K(+) infusion did not significantly
      increase plasma [K(+)]. Thus, when the intragastric K(+) infusion was combined
      with a meal, there was marked enhancement of clearance of the K(+) infused, which
      was associated with an apparent increase in renal efficiency of K(+) excretion.
      These data suggest that there may be a gut factor that enhances renal efficiency
      of K(+) excretion during meal (or dietary K(+)) intake.

PMID- 17522263
TI  - The alternative pathway of complement is activated in the glomeruli and
      tubulointerstitium of mice with adriamycin nephropathy.
AB  - The complement system effectively identifies and clears invasive pathogens as
      well as injured host cells. Uncontrolled complement activation can also
      contribute to tissue injury, however, and inhibition of this system may
      ameliorate many types of inflammatory injury. Several studies have demonstrated
      that the filtration of complement proteins into the renal tubules, as occurs
      during proteinuric renal disease, causes tubular inflammation and injury. In the
      present study, we tested the hypothesis that activation of the complement system
      in the urinary space requires an intact alternative pathway. Using a model of
      adriamycin-induced renal injury, which induces injury resembling focal segmental
      glomerulosclerosis, we examined whether mice deficient in factor B would be
      protected from the development of progressive tubulointerstitial injury.
      Complement activation was attenuated in the glomeruli and tubulointerstitium of
      mice with congenital deficiency of factor B (fB-/-) compared with wild-type
      controls, demonstrating that complement activation does occur through the
      alternative pathway. Deficiency in factor B did not significantly protect the
      mice from tubulointerstitial injury. However, treatment of wild-type mice with an
      inhibitory monoclonal antibody to factor B did delay the development of renal
      failure. These results demonstrate that complement activation in this nonimmune
      complex-mediated model of progressive renal disease requires an intact
      alternative pathway.

PMID- 17522264
TI  - Effects on protein kinase C-beta inhibition on glomerular vascular endothelial
      growth factor expression and endothelial cells in advanced experimental diabetic
      nephropathy.
AB  - Ruboxistaurin is an inhibitor of the beta isoform of protein kinase C (PKC-beta)
      that reduces the actions of vascular endothelial growth factor (VEGF) and
      attenuates the progression of diabetic retinopathy. In the glomerulus VEGF is
      constitutively expressed where it likely has a role in maintaining endothelial
      cell integrity, particularly in disease states. Given its potential use in
      diabetic nephropathy, we sought to determine the effects of PKC-beta inhibition
      on VEGF and glomerular endothelial cells in experimental diabetic nephropathy.
      Studies were conducted in (mRen-2)27 rat, a transgenic rodent with hypertension
      and an enhanced renin-angiotensin system that following induction of diabetes
      with streptozotocin develops many of the features of diabetic nephropathy.
      Moreover, to mimic the clinical context, the effects of PKC-beta inhibition were
      examined both with and without concomitant angiotensin-converting enzyme (ACE)
      inhibitor therapy. Diabetic Ren-2 rats were randomized to receive either vehicle,
      the ACE inhibitor, perindopril (0.2 mg/l in drinking water), ruboxistaurin (10
      mg.kg(-1).day(-1), admixed in chow), or their combination and studied for 12 wk.
      Diabetic Ren-2 rats displayed glomerular endothelial cell loss in association
      with overexpression of VEGF mRNA. Both cell loss and VEGF overexpression were
      attenuated by the administration of either perindopril or ruboxistaurin, as
      single agent treatments with their combination providing additional, incremental
      improvements, reducing these manifestations of injury down to levels seen in
      nondiabetic, normotensive, nontransgenic animals. Combination therapy was also
      associated with additional improvements in albuminuria and glomerulosclerosis.

PMID- 17522265
TI  - Dietary sodium chloride intake independently predicts the degree of
      hyperchloremic metabolic acidosis in healthy humans consuming a net acid
      producing diet.
AB  - We previously demonstrated that typical American net acid-producing diets predict
      a low-grade metabolic acidosis of severity proportional to the diet net acid load
      as indexed by the steady-state renal net acid excretion rate (NAE). We now
      investigate whether a sodium (Na) chloride (Cl) containing diet likewise
      associates with a low-grade metabolic acidosis of severity proportional to the
      sodium chloride content of the diet as indexed by the steady-state Na and Cl
      excretion rates. In the steady-state preintervention periods of our previously
      reported studies comprising 77 healthy subjects, we averaged in each subject
      three to six values of blood hydrogen ion concentration ([H]b), plasma
      bicarbonate concentration ([HCO(3)(-)]p), the partial pressure of carbon dioxide
      (Pco(2)), the urinary excretion rates of Na, Cl, NAE, and renal function as
      measured by creatinine clearance (CrCl), and performed multivariate analyses.
      Dietary Cl strongly correlated positively with dietary Na (P < 0.001) and was an
      independent negative predictor of [HCO(3)(-)]p after adjustment for diet net acid
      load, Pco(2) and CrCl, and positive and negative predictors, respectively, of
      [H]b and [HCO(3)(-)]p after adjustment for diet acid load and Pco(2). These data
      provide the first evidence that, in healthy humans, the diet loads of NaCl and
      net acid independently predict systemic acid-base status, with increasing degrees
      of low-grade hyperchloremic metabolic acidosis as the loads increase. Assuming a
      causal relationship, over their respective ranges of variation, NaCl has
      approximately 50-100% of the acidosis-producing effect of the diet net acid load.

PMID- 17522266
TI  - Metabolic inhibition-induced transient Ca2+ increase depends on mitochondria in a
      human proximal renal cell line.
AB  - During ischemia or hypoxia an increase in intracellular cytosolic Ca(2+) induces
      deleterious events but is also implicated in signaling processes triggered in
      such conditions. In MDCK cells (distal tubular origin), it was shown that
      mitochondria confer protection during metabolic inhibition (MI), by buffering the
      Ca(2+) overload via mitochondrial Na(+)-Ca(2+) exchanger (NCX). To further assess
      this process in cells of human origin, human cortical renal epithelial cells
      (proximal tubular origin) were subjected to MI and changes in cytosolic Ca(2+)
      ([Ca(2+)](i)), Na(+), and ATP concentrations were monitored. MI was accomplished
      with both antimycin A and 2-deoxyglucose and induced a 3.5-fold increase in
      [Ca(2+)](i), reaching 136.5 +/- 15.8 nM in the first 3.45 min. Subsequently
      [Ca(2+)](i) dropped and stabilized to 62.7 +/- 7.3 nM by 30 min. The first phase
      of the transient increase was La(3+) sensitive, not influenced by diltiazem, and
      abolished when mitochondria were deenergized with the protonophore
      carbonylcyanide p-trifluoromethoxyphenylhydrazone. The subsequent recovery phase
      was impaired in a Na(+)-free medium and weakened when the mitochondrial NCX was
      blocked with 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one
      (CGP-37157). Thus Ca(2+) entry is likely mediated by store-operated Ca(2+)
      channels and depends on energized mitochondria, whereas [Ca(2+)](i) recovery
      relied partially on the activity of mitochondrial NCX. These results indicate a
      possible mitochondrial-mediated signaling process triggered by MI, support the
      hypothesis that mitochondrial NCX has an important role in the Ca(2+) clearance,
      and overall suggest that mitochondria play a preponderant role in the regulation
      of responses to MI in human renal epithelial cells.

PMID- 17522267
TI  - Isolation and molecular characterization of Aichi viruses from fecal specimens
      collected in Japan, Bangladesh, Thailand, and Vietnam.
AB  - Aichi virus is a new member of the family Picornaviridae, genus Kobuvirus, and is
      associated with human gastroenteritis. This study detected Aichi virus in 28 of
      912 fecal specimens which were negative for rotavirus, adenovirus, norovirus,
      sapovirus, and astrovirus and were collected in Japan, Bangladesh, Thailand, and
      Vietnam during 2002 to 2005.

PMID- 17522268
TI  - Dengue virus detection using whole blood for reverse transcriptase PCR and virus
      isolation.
AB  - Dengue is one of the most important diseases in the tropical and subtropical
      regions of the world, with an estimated 2.5 billion people being at risk.
      Detection of dengue virus infections has great importance for the clinical
      management of patients, surveillance, and clinical trial assessments.
      Traditionally, blood samples are collected in serum separator tubes, processed
      for serum, and then taken to the laboratory for analysis. The use of whole blood
      has the potential advantages of requiring less blood, providing quicker results,
      and perhaps providing better sensitivity during the acute phase of the disease.
      We compared the results obtained by reverse transcriptase PCR (RT-PCR) with blood
      drawn into tubes containing EDTA and those obtained by RT-PCR with blood samples
      in serum separator tubes from 108 individuals clinically suspected of being
      infected with dengue virus. We determined that the extraction of RNA from whole
      blood followed by RT-PCR resulted in a higher detection rate than the use of
      serum or plasma. Using a selection of these samples, we also found that our
      ability to detect virus by direct C6/36 cell culture and mosquito inoculation was
      enhanced by using whole blood but not to the same extent as that seen by the use
      of RT-PCR.

PMID- 17522269
TI  - Cystitis caused by Aeromonas caviae.
AB  - Aeromonas sp. organisms rarely cause urinary tract infection. We report for the
      first time a case of urinary tract infection caused by A. caviae in an adult
      patient with a history of increased frequency of urination, dysuria, hematuria,
      and weight loss.

PMID- 17522270
TI  - Prophage sequences defining hot spots of genome variation in Salmonella enterica
      serovar Typhimurium can be used to discriminate between field isolates.
AB  - Sixty-one Salmonella enterica serovar Typhimurium isolates of animal and human
      origin, matched by phage type, antimicrobial resistance pattern, and place of
      isolation, were analyzed by microbiological and molecular techniques, including
      pulsed-field gel electrophoresis (PFGE) and plasmid profiling. PFGE identified 10
      profiles that clustered by phage type and antibiotic resistance pattern with
      human and animal isolates distributed among different PFGE profiles. Genomic DNA
      was purified from 23 representative strains and hybridized to the composite
      Salmonella DNA microarray, and specific genomic regions that exhibited
      significant variation between isolates were identified. Bioinformatic analysis
      showed that variable regions of DNA were associated with prophage-like elements.
      Subsequently, simple multiplex PCR assays were designed on the basis of these
      variable regions that could be used to discriminate between S. enterica serovar
      Typhimurium isolates from the same geographical region. These multiplex PCR
      assays, based on prophage-like elements and Salmonella genomic island 1, provide
      a simple method for identifying new variants of S. enterica serovar Typhimurium
      in the field.

PMID- 17522271
TI  - Erythrocyte binding preference of avian influenza H5N1 viruses.
AB  - Five erythrocyte species (horse, goose, chicken, guinea pig, and human) were used
      to agglutinate avian influenza H5N1 viruses by hemagglutination assay and to
      detect specific antibody by hemagglutination inhibition test. We found that goose
      erythrocytes confer a greater advantage over other erythrocyte species in both
      assays.

PMID- 17522272
TI  - Leptotrichia amnionii, an emerging pathogen of the female urogenital tract.
AB  - Leptotrichia amnionii, a recently described, very fastidious, gram-negative
      anaerobic bacterium, is an opportunistic pathogen of the female urogenital tract.
      We report a case of second-trimester abortion in a patient with chorioamnionitis
      and L. amnionii bacteremia and a case of renal abscess in a female 5 weeks
      postpartum.

PMID- 17522273
TI  - Long persistence of methicillin-susceptible strains of Staphylococcus aureus
      causing sepsis in a neonatal intensive care unit.
AB  - Molecular epidemiology of Staphylococcus aureus strains causing bacteremia in
      neonates during 2002 to 2005 revealed seven clones, with four MSSA clones
      responsible for 80% of the cases. Some clones persisted or reappeared throughout
      the study. Three bacteremic clones were found colonizing health care workers
      (HCWs), particularly clone C, which was harbored by at least 15% of HCWs.

PMID- 17522274
TI  - Molecular characterization of methicillin-resistant Staphylococcus aureus
      isolates collected in Asuncion, Paraguay.
AB  - We characterized 34 methicillin-resistant Staphylococcus aureus strains isolated
      in Paraguay in 2005. The strains belonged to two clones. The major clone
      (sequence type 5 [ST5] or ST221, spa type t149, staphylococcal cassette
      chromosome mec [SCCmec] type I) was similar to the Cordobes/Chilean clone
      spreading through South America, and the minor clone (ST239 or ST889, spa type
      t037, SCCmec type IIIA) was related to the Brazilian clone.

PMID- 17522275
TI  - Clinical validation of the molecular BD GeneOhm StaphSR assay for direct
      detection of Staphylococcus aureus and methicillin-resistant Staphylococcus
      aureus in positive blood cultures.
AB  - The rapid detection of Staphylococcus aureus bacteremia and a swift determination
      of methicillin susceptibility has serious clinical implications affecting patient
      mortality. This study evaluated the StaphSR assay (BD GeneOhm, San Diego, CA), a
      real-time PCR assay, for the identification and differentiation of methicillin
      susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) from 300
      positive blood cultures. The BD GeneOhm StaphSR assay was performed and
      interpreted according to the manufacturer's recommendations. Positive blood
      cultures (containing predominantly gram-positive cocci in clusters) were
      subcultured on 5% sheep blood agar plates. After 18 to 24 h of incubation,
      isolates morphologically consistent with S. aureus were presumptively identified
      by latex agglutination (Staphaurex Plus; Remel, Lenexa, KS). Susceptibility
      testing was initially performed with the Phoenix automated microbiology system
      (BD Diagnostics, Sparks, MD). Additional susceptibility testing of samples with
      discrepant results was done using BBL oxacillin screen agar (BD Diagnostics,
      Sparks, MD), oxacillin and cefoxitin Etests (AB Biodisk, Solna, Sweden) on
      Mueller-Hinton agar, an immunoassay for penicillin binding protein 2' (Denka
      Seiken Co., Tokyo, Japan), and mecA PCR. The sensitivity, specificity, and
      positive and negative predictive values of the BD GeneOhm StaphSR assay for MSSA
      detection were 98.9, 96.7, 93.6, and 99.5%, respectively. For the detection of
      MRSA, the BD GeneOhm StaphSR assay was 100% sensitive and 98.4% specific;
      positive and negative predictive values for MRSA detection were 92.6 and 100%,
      respectively. Inhibition was seen with only one sample, and the issue was
      resolved upon retesting. The BD GeneOhm StaphSR assay appears to be a valuable
      diagnostic tool for quickly differentiating bacteremia caused by MSSA and MRSA
      from that caused by other gram-positive cocci.

PMID- 17522276
TI  - RTX toxin actin cross-linking activity in clinical and environmental isolates of
      Vibrio cholerae.
AB  - Vibrio cholerae strains from diverse O-antigen groups were evaluated for RTX
      toxin actin cross-linking activity. This study demonstrates that the actin cross
      linking domain sequence is present within rtxA in the majority of clinical and
      environmental isolates tested, and the RTX toxin produced by these strains
      catalyzes the covalent cross-linking of cellular actin.

PMID- 17522277
TI  - Validation and reproducibility assessment of tigecycline MIC determinations by
      Etest.
AB  - A multicenter study was conducted to validate Etest tigecycline compared to the
      Clinical Laboratory Standards Institute reference broth microdilution and agar
      dilution methodologies. A large collection of gram-negative (n = 266) and gram
      positive (n = 162) aerobic bacteria, a collection of anaerobes (n = 385), and
      selected collections of nonpneumococcal streptococci (n = 369), Streptococcus
      pneumoniae (n = 372), and Haemophilus influenzae (n = 372) were tested. Strains
      with reduced susceptibility to tigecycline were used with all test methods. The
      Etest showed excellent inter- and intralaboratory reproducibility for all
      organism groups tested regardless of the test methodology. The essential
      agreement values with the reference method (+/-1 dilution) were >99% for the
      collection of gram-negative and gram-positive aerobes; >98% for the S.
      pneumoniae, H. influenzae, and anaerobe collections; and 100% for the group of
      nonpneumococcal streptococci. These results validate the performance accuracy and
      utility of Etest tigecycline and verify the reproducibility of this convenient
      predefined gradient methodology for tigecycline susceptibility determination.

PMID- 17522278
TI  - Limited applicability of direct fluorescent-antibody testing for Bordetella sp.
      and Legionella sp. specimens for the clinical microbiology laboratory.
AB  - The rapid diagnosis of infections with Bordetella and Legionella species is
      important for patient management. With observed increases in direct fluorescent
      antibody (DFA) testing volumes, we retrospectively compared the performance
      characteristics of DFA testing to those of culture and PCR. For Bordetella sp.,
      samples were classified as positive by DFA testing (184 [3%] of 6,195 samples)
      and culture (150 [2%] of 6,251 samples) significantly less often than by PCR
      (2,557 [10%] of 26,929 samples). Of 360 samples tested by both DFA and PCR
      methods, 81 (16 by DFA testing and 79 by PCR) were determined to be positive for
      Bordetella, with a sensitivity and specificity of DFA testing of 18% and 99%,
      respectively. Of 1,426 samples tested by both DFA and culture methods, 48 (44 by
      DFA testing and 15 by culture) were determined to be positive for Bordetella,
      with a sensitivity and specificity of DFA testing of 73% and 98%, respectively.
      For Legionella sp., samples were identified as positive by DFA testing (31
      [0.25%] of 12,597 samples) and culture (85 [0.6%] of 13,572 samples)
      significantly less often than by PCR (27 [4%] of 716 samples). Of 62 samples
      tested by both DFA and PCR methods, none were positive for Legionella sp. by DFA
      testing and 3 were positive by PCR. Of 3,923 samples tested by both DFA and
      culture methods, 22 (3 by DFA testing and 21 by culture) were positive for
      Legionella sp., with a sensitivity and specificity of DFA testing of 9.5% and
      100%. Overall, DFA testing for Bordetella sp. and Legionella sp. is an
      insensitive method, and despite its continued popularity, clinical microbiology
      laboratories should not offer it when more sensitive tests like PCR are
      available.

PMID- 17522279
TI  - Comparison of two versions of the IDI-MRSA assay using charcoal swabs for
      prospective nasal and nonnasal surveillance samples.
AB  - An updated IDI-MRSA assay version was released to address the assay's low
      positive predictive value (PPV). A prospective analysis of two assay versions
      indicated no significant improvement in the PPV. Colonization by methicillin
      resistant Staphylococcus aureus in 24% of patients would not have been detected
      if only nasal samples had been tested, as approved, by this molecular method.

PMID- 17522280
TI  - Rapid identification of Staphylococcus aureus in blood cultures by use of the
      direct tube coagulase test.
AB  - Direct tube coagulase testing for identification of Staphylococcus aureus from
      BACTEC culture broth showed a sensitivity, a specificity, and positive and
      negative predicative values of 34%, 100%, 100%, and 80.2% with 2 h of incubation
      and 65%, 98.7, 99.7%, and 88.6% with 4 h of incubation. Anaerobic blood culture
      contributed significantly to the detection of S. aureus.

PMID- 17522281
TI  - Systems approach to improving antimicrobial susceptibility testing in clinical
      laboratories in the United States.
AB  - Laboratory practice in the preanalytical phase of antimicrobial susceptibility
      testing (AST) was evaluated in 102 hospital, reference, physician office-clinic,
      and public health laboratories in Washington state. Surveys were sent to evaluate
      (i) use of NCCLS/CLSI (formerly NCCLS) AST performance standards, (ii) technical
      competence in AST case studies, challenging knowledge of contemporary testing
      issues, and (iii) choice of antimicrobial agents to test for Streptococcus
      pneumoniae. Numerous deficiencies were identified in the survey: (i) initially
      only 40% of the laboratories surveyed used current NCCLS/CLSI AST performance
      standards, (ii) the rate of accurate responses for three different case studies
      ranged from 29% to 69%, and (iii) variation was noted in the choice of
      antimicrobials tested against invasive isolates of S. pneumoniae. These
      deficiencies could affect therapy and detection of antimicrobial resistance.
      Several educational programs were implemented to improve AST policies and
      practices, and a follow-up survey indicated that four intervention strategies
      were most effective: (i) regional technical workshops, (ii) National Laboratory
      Training Network teleconferences, (iii) use of the Centers for Disease Control
      and Prevention (CDC) CD-ROM on AST, and (iv) the CDC Multilevel Antimicrobial
      Susceptibility Testing Resource website. The interventions could be implemented
      more widely in the United States to improve AST knowledge and practices.

PMID- 17522282
TI  - A rash.

PMID- 17522283
TI  - Widespread vesiculobullous eruption in an infant.

PMID- 17522284
TI  - Hyperpigmentation.

PMID- 17522285
TI  - Improvement in provider immunization knowledge and behaviors following a peer
      education intervention.
AB  - Provider education programs that use academic detailing to improve childhood
      immunization have been implemented in several states. The purpose of this study
      was to evaluate the impact of these types of programs to improve immunization
      related behaviors in private provider offices. The intervention included peer
      based academic detailing in which teams of 1 physician, 1 nurse, and 1 office
      manager visited pediatric and family practices to deliver an educational
      presentation and develop practice-specific action plans. Comparison of pre-post
      intervention surveys showed that providers' willingness to give the maximum
      number of immunizations due at 1 visit (P < .001) increased. More providers
      reported routinely screening immunization records at sickness or injury visits (P
      < .05) and using minimum intervals (P < .001) postintervention. Mean change in
      baseline and postintervention overall scores was significant for pediatric
      practices (0.40, P < .05), small practices (0.64, P < .01), Vaccines for Children
      (VFC) practices (0.74, P < .05), and non-VFC provider practices (0.67, P < .01)
      but not for family or large practices.

PMID- 17522286
TI  - Prader-Willi syndrome: an update and review for the primary pediatrician.
AB  - Prader-Willi syndrome, the first known human genomic imprinting disorder, is one
      of the most common micro-deletion syndromes. Prader-Willi syndrome is caused by
      the absence of certain paternally inherited genes on the long arm of chromosome
      15, resulting in a complete absence of the active copy of the genetic information
      in this region. It is most commonly known for its food-related characteristics of
      hyperphagia, food-seeking behavior, and consequent obesity. Primary care
      physicians play an important role in the care of children with Prader-Willi
      syndrome, from recognizing the presenting signs and symptoms at its various
      stages to understanding their unique medical, developmental, behavioral, and
      dietary issues. They can also serve as a valuable source of support and advocacy
      for the family. This article reviews the current state of knowledge about Prader
      Willi syndrome and discusses up-to-date understanding of the management of this
      condition.

PMID- 17522287
TI  - Elevator-related injuries to children in the United States, 1990 through 2004.
AB  - This study describes the epidemiology of elevator-related injuries among children
      in the United States from 1990 to 2004. A retrospective cohort analysis was
      performed using data from the National Electronic Injury Surveillance System of
      the US Consumer Product Safety Commission. Reported cases were used to project
      national estimates. An estimated 29 030 elevator-related injuries occurred among
      children in the United States during 1990 to 2004. The mean age was 8.1 years
      (SD, 6.1 years), with 53.3% of injuries among boys. The overall injury rate was
      2.5 injuries per 100,000 population. The injury rate for children aged 0-4 years
      was 4.2 per 100,000 population, and for children aged 5-19 years the injury rate
      was 1.9 per 100,000 population. The most frequent cause of injury was the
      elevator door closing on a body part, the most frequently injured body region was
      the upper extremity, and soft-tissue injuries were the most frequent type of
      injury. Children should be closely supervised on or near elevators to reduce the
      risk of injury.

PMID- 17522288
TI  - Fine motor function and oral-motor imitation skills in preschool-age children
      with speech-sound disorders.
AB  - Preschool-aged children with speech-sound disorders may be at risk for associated
      deficits in fine motor function. The objectives of this study were 2-fold: (1) to
      determine whether abnormalities in fine motor function could be detected in 2- to
      5-year-old children with speech-sound disorders and (2) to determine whether
      there was a correlation between abnormal oral-motor imitation skills and abnormal
      fine motor function. Thirty-two children with speech-sound disorders (6 female,
      26 male) were prospectively evaluated from July 2003 to July 2005, and the
      Peabody Developmental Motor Scales and the Kaufman Speech Praxis Test for
      Children were administered. The presence of abnormal oral-motor imitation skills
      as measured by the Kaufman Speech Praxis Test was associated with below-average
      fine motor performance. This finding has important implications for evaluation
      and treatment of preschool children with severe speech-sound disorders.

PMID- 17522289
TI  - Variability in the evaluation and management of opiate-exposed newborns in
      Maryland.
AB  - During 2003 and 2004 an estimated 2000 pregnant women and 31 000 nonpregnant
      women aged 15 to 44 reported using heroin. The majority of those newborns exposed
      in utero to opioids will develop symptoms of neonatal abstinence syndrome (NAS).
      Standardized guidelines for the evaluation and management of opiate-exposed
      newborns are lacking. The objective of this study was to document variations in
      the evaluation and management of opiate-exposed newborns among Maryland hospitals
      using a 13-item phone survey. Twenty-seven (82%) of the hospitals completed the
      survey. Staff at every hospital reported that they delivered opiate-exposed
      infants, however only 52% reported using a standardized evaluation and treatment
      protocol for this population consisting of guidelines for maternal toxicology
      screening, length-of-stay criteria and a monitoring tool for drug-exposed
      infants, infant supportive care techniques, and pharmacologic treatment
      guidelines. Significant variability exists in the evaluation and management of
      opiate-exposed newborns in Maryland. Validated, evidence-based guidelines are
      needed to standardize the care of these vulnerable newborns across all hospital
      settings.

PMID- 17522290
TI  - Tioga County Fit for Life: a primary obesity prevention project.
AB  - Pediatric obesity, which has reached epidemic proportions in the United States in
      the past 10 years, translates directly into rising rates of adult obesity. This
      study assessed the impact of a school, family, community, and industry-based
      primary intervention project on the rates of overweight and obesity in a rural
      countywide cohort of children in grades kindergarten through 8. It included
      classroom education, student/ family wellness booklets, point source healthy
      menus, occupational health analyses, and community health fairs. A 5-year
      longitudinal analysis of grade-specific rates of overweight and obesity of the
      participating children showed that overweight and obesity rates increased for all
      cohorts. Key elements contribute to increasing rates of pediatric obesity.
      Inadequate penetration of education/information dissemination and lag time
      represent 2 explanations for the lack of obesity reduction during the program
      implementation period. Strategies for successful engagement of multiple groups
      are essential to effectively reverse the pediatric obesity epidemic.

PMID- 17522291
TI  - An important issue in the management of elimination dysfunction in children:
      parental awareness of constipation.
AB  - The scale of parental awareness concerning children's bowel habits and its
      effects on voiding dysfunction were investigated. Parents of toilet-trained
      children older than 4 years were given questionnaires during the first interview
      and after follow-up of their children's bowel habits for symptoms and signs of
      constipation and urinary complaints. Diagnosis of constipation was made according
      to the Rome III criteria. Eighty-nine patients were included in the study. The
      number of constipated patients almost doubled after the observation period. Most
      of the urinary problems resolved upon treatment of constipation. History at first
      interview was misleading in 42% of the patients who would benefit from a simple
      treatment. Most of the parents were unaware of their children's bowel habits.
      Before proceeding with more complicated tests or treatment of voiding
      dysfunction, the symptoms and signs of constipation should be sought during a
      close parental observation period.

PMID- 17522292
TI  - Pertussis symptoms in adolescents and children versus infants: the influence of
      vaccination and age.
AB  - This study compared the influence of age and immunization status on symptoms in
      pediatric patients with pertussis. The files of 60 children, aged 7 to 18 years
      and 20 infants aged up to 6 months, admitted to our pediatric hospital with a
      diagnosis of pertussis were reviewed. There were no between-group differences in
      day and night cough or vomiting. The older group had a longer mean interval to
      diagnosis than the infants, and the infant group had more symptoms of whooping
      cough, facial redness during cough, cyanosis, a higher white blood count, a
      higher percentage of lymphocytes, and more abnormal chest X-rays. Statistically
      significant differences were found between vaccinated and unvaccinated older
      children for whooping cough and white blood cell count. Daytime and nighttime
      coughs are common symptoms of pertussis in all pediatric age groups, regardless
      of vaccination status. High white blood count is related to immunization status,
      and percentage of lymphocytes is related to age. In infants, symptoms are more
      grave but are typical, leading to early diagnosis.

PMID- 17522298
TI  - Mind the GAP: a role for neurofibromin in restricting axonal plasticity.

PMID- 17522299
TI  - Sodium valproate exerts neuroprotective effects in vivo through CREB-binding
      protein-dependent mechanisms but does not improve survival in an amyotrophic
      lateral sclerosis mouse model.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by motoneuron (MN)
      degeneration, generalized weakness, and muscle atrophy. The premature death of
      MNs is thought to be a determinant in the onset of this disease. In a transgenic
      mouse model of ALS expressing the G86R mutant superoxide dismutase 1 (mSOD1), we
      demonstrated previously that CREB (cAMP response element-binding protein)-binding
      protein (CBP) and histone acetylation levels were specifically decreased in
      nuclei of degenerating MNs. We show here that oxidative stress and mSOD1
      overexpression can both impinge on CBP levels by transcriptional repression, in
      an MN-derived cell line. Histone deacetylase inhibitor (HDACi) treatment was able
      to reset proper acetylation levels and displayed an efficient neuroprotective
      capacity against oxidative stress in vitro. Interestingly, HDACi also upregulated
      CBP transcriptional expression in MNs. Moreover, when injected to G86R mice in
      vivo, the HDACi sodium valproate (VPA) maintained normal acetylation levels in
      the spinal cord, efficiently restored CBP levels in MNs, and significantly
      prevented MN death in these animals. However, despite neuroprotection, mean
      survival of treated animals was not significantly improved (<5%), and they died
      presenting the classical ALS symptoms. VPA was not able to prevent disruption of
      neuromuscular junctions, although it slightly delayed the onset of motor decline
      and retarded muscular atrophy to some extent. Together, these data show that
      neuroprotection can improve disease onset, but clearly provide evidence that one
      can uncouple MN survival from whole-animal survival and point to the
      neuromuscular junction perturbation as a primary event of ALS onset.

PMID- 17522300
TI  - A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and
      ectopic neurons, reduced myelination, seizure activity, and limited survival.
AB  - Tuberous sclerosis (TSC) is a hamartoma syndrome caused by mutations in TSC1 or
      TSC2 in which cerebral cortical tubers and seizures are major clinical issues. We
      have engineered mice in which most cortical neurons lose Tsc1 expression during
      embryonic development. These Tsc1 mutant mice display several neurological
      abnormalities beginning at postnatal day 5 with subsequent failure to thrive and
      median survival of 35 d. The mice also display clinical and electrographic
      seizures both spontaneously and with physical stimulation, and some seizures end
      in a fatal tonic phase. Many cortical and hippocampal neurons are enlarged and/or
      dysplastic in the Tsc1 mutant mice, strongly express phospho-S6, and are ectopic
      in multiple sites in the cortex and hippocampus. There is a striking delay in
      myelination in the mutant mice, which appears to be caused by an inductive
      neuronal defect. This new TSC brain model replicates several features of human
      TSC brain lesions and implicates an important function of Tsc1/Tsc2 in neuronal
      development.

PMID- 17522301
TI  - Linking synaptic plasticity and spike output at excitatory and inhibitory
      synapses onto cerebellar Purkinje cells.
AB  - Understanding the relationship between synaptic plasticity and neuronal output is
      essential if we are to understand how plasticity is encoded in neural circuits.
      In the cerebellar cortex, motor learning is thought to be implemented by long
      term depression (LTD) of excitatory parallel fiber (PF) to Purkinje cell synapses
      triggered by climbing fiber (CF) input. However, theories of motor learning
      generally neglect the contribution of plasticity of inhibitory inputs to Purkinje
      cells. Here we describe how CF-induced plasticity of both excitatory and
      inhibitory inputs is reflected in Purkinje cell spike output. We show that
      coactivation of the CF with PF input and interneuron input leads not only to LTD
      of PF synapses but also to comparable, "balanced" LTD of evoked inhibitory
      inputs. These two forms of plasticity have opposite effects on the spike output
      of Purkinje cells, with the number and timing of spikes sensitively reflecting
      the degree of plasticity. We used dynamic clamp to evaluate plasticity-induced
      changes in spike responses to sequences of excitation and feedforward inhibition
      of varied relative and absolute amplitude. Balanced LTD of both excitatory and
      inhibitory components decreased the net spike output of Purkinje cells only for
      inputs with small inhibitory components, whereas for inputs with a larger
      proportion of feedforward inhibition CF-triggered LTD resulted in an increase in
      the net spike output. Thus, the net effect of CF-triggered plasticity on Purkinje
      cell output depends on the balance of excitation and feedforward inhibition and
      can paradoxically increase cerebellar output, contrary to current theories of
      cerebellar motor learning.

PMID- 17522302
TI  - Translocation of Gq alpha mediates long-term adaptation in Drosophila
      photoreceptors.
AB  - Light adaptation is a process that enables photoreceptor cells to operate over a
      wide range of light intensities without saturation. In invertebrate
      photoreceptors, fast adaptation is mediated by a Ca2+-dependent negative-feedback
      mechanism, which mainly affects the terminal steps of the cascade. Therefore, the
      response to each photon is smaller as light intensity increases, accommodating
      both high sensitivity and a vast dynamic range. Here, we describe a novel type of
      adaptation, which is mediated by one of the first steps in the phototransduction
      cascade affecting the sensitivity to absorbed photons. Long exposure to light
      resulted in dramatic reduction in the probability of each absorbed photon to
      elicit a response, whereas the size and shape of each single photon response did
      not change. To dissect the molecular mechanism underlying this form of adaptation
      we used a series of Drosophila mutants. Genetic dissection showed a pivotal role
      for light-induced translocation of Gq alpha between the signaling membrane and
      the cytosol. Biochemical studies revealed that the sensitivity to light depends
      on membrane Gq alpha concentration, which was modulated either by light or by
      mutations that impaired its targeting to the membrane. We conclude that long-term
      adaptation is mediated by the movement of Gq alpha from the signaling membrane to
      the cytosol, thereby reducing the probability of each photon to elicit a
      response. The slow time scale of this adaptation fits well with day/night light
      intensity changes, because there is no need to maintain single photon sensitivity
      during daytime.

PMID- 17522303
TI  - Characterization of ligands for fish taste receptors.
AB  - Recent progress in the molecular biology of taste reception has revealed that in
      mammals, the heteromeric receptors T1R1/3 and T1R2/3 respond to amino acids and
      sweeteners, respectively, whereas T2Rs are receptors for bitter tastants. Similar
      taste receptors have also been characterized in fish, but their ligands have not
      been identified yet. In the present study, we conducted a series of experiments
      to identify the fish taste receptor ligands. Facial nerve recordings in zebrafish
      (Danio rerio) demonstrated that the fish perceived amino acids and even
      denatonium, which is a representative of aversive bitter compounds for mammals
      and Drosophila. Calcium imaging analysis of T1Rs in zebrafish and medaka fish
      (Oryzias latipes) using an HEK293T heterologous expression system revealed that
      both T1R1/3 and a series of T1R2/3 responded to amino acids but not to sugars. A
      triple-labeling, in situ hybridization analysis demonstrated that cells
      expressing T1R1/3 and T1R2/3s exist in PLCbeta2-expressing taste bud cells of
      medaka fish. Functional analysis using T2Rs showed that zfT2R5 and mfT2R1
      responded to denatonium. Behavior observations confirmed that zebrafish prefer
      amino acids and avoid denatonium. These results suggest that, although there may
      be some fish-specific way of discriminating ligands, vertebrates could have a
      conserved gustatory mechanism by which T1Rs and T2Rs respond to attractive and
      aversive tastants, respectively.

PMID- 17522304
TI  - Primate reaching cued by multichannel spatiotemporal cortical microstimulation.
AB  - Both humans and animals can discriminate signals delivered to sensory areas of
      their brains using electrical microstimulation. This opens the possibility of
      creating an artificial sensory channel that could be implemented in
      neuroprosthetic devices. Although microstimulation delivered through multiple
      implanted electrodes could be beneficial for this purpose, appropriate
      microstimulation protocols have not been developed. Here, we report a series of
      experiments in which owl monkeys performed reaching movements guided by
      spatiotemporal patterns of cortical microstimulation delivered to primary
      somatosensory cortex through chronically implanted multielectrode arrays. The
      monkeys learned to discriminate microstimulation patterns, and their ability to
      learn new patterns and new behavioral rules improved during several months of
      testing. Significantly, information was conveyed to the brain through the
      interplay of microstimulation patterns delivered to multiple electrodes and the
      temporal order in which these electrodes were stimulated. This suggests
      multichannel microstimulation as a viable means of sensorizing neural prostheses.

PMID- 17522305
TI  - Glial cell line-derived neurotrophic factor and neurturin inhibit neurite
      outgrowth and activate RhoA through GFR alpha 2b, an alternatively spliced
      isoform of GFR alpha 2.
AB  - The glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) belong
      to a structurally related family of neurotrophic factors. NTN exerts its effect
      through a multicomponent receptor system consisting of the GDNF family receptor
      alpha2 (GFR alpha2), RET, and/or NCAM (neural cell adhesion molecule). GFR alpha2
      is alternatively spliced into at least three isoforms (GFR alpha2a, GFR alpha2b,
      and GFR alpha2c). It is currently unknown whether these isoforms share similar
      functional and biochemical properties. Using highly specific and sensitive
      quantitative real-time PCR, these isoforms were found to be expressed at
      comparable levels in various regions of the human brain. When stimulated with
      GDNF and NTN, both GFR alpha2a and GFR alpha2c, but not GFR alpha2b, promoted
      neurite outgrowth in transfected Neuro2A cells. These isoforms showed ligand
      selectivity in MAPK (mitogen-activated protein kinase) [ERK1/2 (extracellular
      signal-regulated kinase 1/2)] and Akt signaling. In addition, the GFR alpha2
      isoforms regulated different early-response genes when stimulated with GDNF or
      NTN. In coexpression studies, GFR alpha2b was found to inhibit ligand-induced
      neurite outgrowth by GFR alpha2a and GFR alpha2c. Stimulation of GFR alpha2b also
      inhibited the neurite outgrowth induced by GFR alpha1a, another member of the GFR
      alpha. Furthermore, activation of GFR alpha2b inhibited neurite outgrowth induced
      by retinoic acid and activated RhoA. Together, these data suggest a novel
      paradigm for the regulation of growth factor signaling and neurite outgrowth via
      an inhibitory splice variant of the receptor. Thus, depending on the expressions
      of specific GFR alpha2 receptor spliced isoforms, GDNF and NTN may promote or
      inhibit neurite outgrowth through the multicomponent receptor complex.

PMID- 17522306
TI  - Nicotinic alpha 7 receptors as a new target for treatment of cannabis abuse.
AB  - Increasing use of cannabis makes the search for medications to reduce cannabis
      abuse extremely important. Here, we show that homomeric alpha7 nicotinic
      receptors are novel molecular entities that could be targeted in the development
      of new drugs for the treatment of cannabis dependence. In rats, systemic
      administration of the selective alpha7 nicotinic acetylcholine receptor
      antagonist methyllycaconitine (MLA), but not the selective heteromeric non-alpha7
      nicotinic acetylcholine receptor antagonist dihydrobetaerythroidine, (1)
      antagonized the discriminative effects of delta-9-tetrahydrocannabinol (THC), the
      main active ingredient in cannabis, (2) reduced intravenous self-administration
      of the synthetic cannabinoid CB1 receptor agonist WIN55,212-2 [(R)-(+)-[2,3
      dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1
      naphthalenyl)methanone, mesylate salt], and (3) decreased THC-induced dopamine
      elevations in the shell of the nucleus accumbens. Altogether, our results
      indicate that blockade of alpha7 nicotinic receptors reverses abuse-related
      behavioral and neurochemical effects of cannabinoids. Importantly, MLA reversed
      the effects of cannabinoids at doses that did not produce depressant or toxic
      effects, further pointing to alpha7 nicotinic antagonists as potentially useful
      agents in the treatment of cannabis abuse in humans.

PMID- 17522307
TI  - Multiple modes of synaptic excitation of olfactory bulb granule cells.
AB  - Inhibition generated by granule cells, the most common GABAergic cell type in the
      olfactory bulb, plays a critical role in shaping the output of the olfactory
      bulb. However, relatively little is known about the synaptic mechanisms
      responsible for activating these interneurons in addition to the specialized
      dendrodendritic synapses located on distal dendrites. Using two-photon guided
      minimal stimulation in acute rat brain slices, we found that distal and proximal
      excitatory synapses onto granule cells are functionally distinct. Proximal
      synapses arise from piriform cortical neurons and facilitate with paired-pulse
      stimulation, whereas distal dendrodendritic synapses generate EPSCs with slower
      kinetics that depress with paired stimulation. Proximal cortical feedback inputs
      can relieve the tonic Mg block of NMDA receptors (NMDARs) at distal synapses and
      gate dendrodendritic inhibition onto mitral cells. Most excitatory synapses we
      examined onto granule cells activated both NMDARs and AMPA receptors, whereas a
      subpopulation appeared to be NMDAR silent. The convergence of two types of
      excitatory inputs onto GABAergic granule cells provides a novel mechanism for
      regulating the degree of interglomerular processing of sensory input in the
      olfactory bulb through piriform cortex/olfactory bulb synaptic interactions.

PMID- 17522308
TI  - Functional characterization of intrinsic cholinergic interneurons in the cortex.
AB  - Acetylcholine is a major neurotransmitter that modulates cortical functions. In
      addition to basal forebrain neurons that give rise to the principal cholinergic
      input into the cortex, a second source constituted by intrinsic cholinergic
      interneurons has been identified. Although these cells have been characterized
      anatomically, little is known about their functional role in cortical
      microcircuits. The paucity of this cell population has been a major hindrance for
      detailed electrophysiological investigations. To facilitate functional studies,
      we generated transgenic mice that express enhanced green fluorescent protein
      (EGFP) in choline acetyltransferase (ChAT)-positive neurons. Aided by the
      transgene expression, the characterization of distinct cholinergic interneurons
      was possible. These cells were located in layer 2-3, had a bipolar morphology,
      were calretinin- and vasoactive intestinal peptide positive, but had a non
      GABAergic phenotype. Paired recordings showed that EGFP/ChAT-positive neurons
      receive excitatory and inhibitory input from adjacent principal cells and various
      types of interneurons. However, EGFP/ChAT-positive neurons do not exert direct
      postsynaptic responses in neighboring neurons. Interestingly, prolonged
      activation of EGFP-labeled cholinergic neurons induces an increase in spontaneous
      EPSCs in adjacent pyramidal neurons. This indirect effect is mediated by
      nicotinic receptors that are presumably presynaptically localized. Thus,
      intrinsic bipolar cholinergic neurons can modulate cortical function locally.

PMID- 17522309
TI  - Multiple effects of ephrin-A5 on cortical neurons are mediated by SRC family
      kinases.
AB  - The Eph receptor tyrosine kinases and their membrane-bound ligands, the ephrins,
      are involved in a variety of developmental processes such as axonal guidance,
      cell migration, cell adhesion, proliferation, and differentiation. In addition to
      repulsive effects, ephrins can also induce attractive responses. Up to now,
      little was known about the underlying signaling mechanisms that regulate
      attractive versus repulsive effects. In this study, we show that ephrin-A5
      enhances the motility of cortical neurons that is dependent on the activity of
      Src-family kinases (SFKs). Ephrin-A5 further changes the adhesive properties of
      neurons by inducing the formation of cell aggregates. Using the stripe assay, we
      found that the motogenic effect of ephrin-A5 is the result of repulsive ephrin-A
      interactions. Blocking SFK function leads to a conversion of repulsion into
      adhesion, suggesting that SFKs can act as a biological switch for the response of
      EphA receptors. Finally, we discovered a ligand-induced release of membrane
      particles containing EphA receptors, suggesting membrane ripping as a novel
      mechanism to overcome the "ephrin paradox" of repulsion after high-affinity
      receptor-ligand binding.

PMID- 17522310
TI  - Activation of group I metabotropic glutamate receptors on main olfactory bulb
      granule cells and periglomerular cells enhances synaptic inhibition of mitral
      cells.
AB  - Granule and periglomerular cells in the main olfactory bulb express group I
      metabotropic glutamate receptors (mGluRs). The group I mGluR agonist 3,4
      dihydroxyphenylglycine (DHPG) increases GABAergic spontaneous IPSCs (sIPSCs) in
      mitral cells, yet the presynaptic mechanism(s) involved and source(s) of the
      IPSCs are unknown. We investigated the actions of DHPG on sIPSCs and TTX
      insensitive miniature IPSCs (mIPSCs) recorded in mitral and external tufted cells
      in rat olfactory bulb slices. DHPG, acting at mGluR1 and mGluR5, increased the
      rate but not amplitude of sIPSCs and mIPSCs in both cell types. The increase in
      mIPSCs depended on voltage-gated Ca2+ channels but persisted when ionotropic
      glutamate receptors and sodium spikes were blocked. Focal DHPG puffs onto granule
      cells or bath application after glomerular layer (GL) excision failed to increase
      mIPSCs in mitral cells. Additionally, GL excision reduced sIPSCs in mitral cells
      by 50%, suggesting that periglomerular cells exert strong tonic GABAergic
      inhibition of mitral cells. In contrast, GL DHPG puffs readily increased mIPSCs.
      These findings indicate that DHPG-evoked GABA release from granule cells requires
      spikes, whereas in the GL, DHPG facilitates periglomerular cell GABA release via
      both spike-dependent and spike-independent presynaptic mechanisms. We speculate
      that mGluRs amplify spike-driven lateral inhibition through the mitral-to-granule
      cell circuit, whereas GL mGluRs may play a more important role in amplifying
      intraglomerular inhibition after subthreshold input.

PMID- 17522311
TI  - Recurrent dendrodendritic inhibition of accessory olfactory bulb mitral cells
      requires activation of group I metabotropic glutamate receptors.
AB  - Metabotropic glutamate receptors (mGluRs) modulate neural excitability and
      network tone in many brain regions. Expression of mGluRs is particularly high in
      the accessory olfactory bulb (AOB), a CNS structure critical for detecting
      chemicals that identify kin and conspecifics. Because of its relative simplicity
      and its direct projection to the hypothalamus, the AOB provides a model system
      for studying how mGluRs affect the flow of encoded sensory information to
      downstream areas. We investigated the role of group I mGluRs in synaptic
      processing in AOB slices and found that under control conditions, recurrent
      inhibition of principal neurons (mitral cells) was completely eliminated by the
      mGluR1 antagonist LY367385 [(S)-(+)-alpha-amino-4-carboxy-2 methylbenzeneacetic
      acid]. In addition, the group I mGluR agonist DHPG [(S)-3,5
      dihydroxyphenylglycine; 20 microM] induced a dramatic increase in the rate of
      spontaneous IPSCs. This increase was dependent on voltage-gated calcium channels
      but persisted even after blockade of ionotropic glutamatergic transmission and
      sodium channels. Together, these results indicate that mGluR1 plays a critical
      role in controlling information flow through the AOB and suggest that mGluR1 may
      be an important locus for experience-dependent changes in synaptic function.

PMID- 17522312
TI  - Impaired motor learning in the vestibulo-ocular reflex in mice with multiple
      climbing fiber input to cerebellar Purkinje cells.
AB  - A unique feature of the cerebellar architecture is that Purkinje cells in the
      cerebellar cortex each receive input from a single climbing fiber. In mice
      deficient in the gamma isoform of protein kinase C (PKCgamma-/- mice), this
      normal architecture is disrupted so that individual Purkinje cells receive input
      from multiple climbing fibers. These mice have no other known abnormalities in
      the cerebellar circuit. Here, we show that PKCgamma-/- mice are profoundly
      impaired in vestibulo-ocular reflex (VOR) motor learning. The PKCgamma-/- mice
      exhibited no adaptive increases or decreases in VOR gain at training frequencies
      of 2 or 0.5 Hz. This impairment was present across a broad range of peak retinal
      slip speeds during training. We compare the results for VOR motor learning with
      previous studies of the performance of PKCgamma-/- mice on other cerebellum
      dependent learning tasks. Together, the results suggest that single climbing
      fiber innervation of Purkinje cells is critical for some, but not all, forms of
      cerebellum-dependent learning, and this may depend on the region of the
      cerebellum involved, the organization of the relevant neural circuits downstream
      of the cerebellar cortex, as well as the timing requirements of the learning
      task.

PMID- 17522314
TI  - Cholinergic modulation of spindle bursts in the neonatal rat visual cortex in
      vivo.
AB  - Acetylcholine (ACh) is known to shape the adult neocortical activity related to
      behavioral states and processing of sensory information. However, the impact of
      cholinergic input on the neonatal neuronal activity remains widely unknown. Early
      during development, the principal activity pattern in the primary visual (V1)
      cortex is the intermittent self-organized spindle burst oscillation that can be
      driven by the retinal waves. Here, we assessed the relationship between this
      early activity pattern and the cholinergic drive by either blocking or augmenting
      the cholinergic input and investigating the resultant effects on the activity of
      the rat visual cortex during the first postnatal week in vivo. Blockade of the
      muscarinic receptors by intracerebroventricular, intracortical, or supracortical
      atropine application decreased the occurrence of V1 spindle bursts by 50%, both
      the retina-independent and the optic nerve-mediated spindle bursts being
      affected. In contrast, blockade of acetylcholine esterase with physostigmine
      augmented the occurrence, amplitude, and duration of V1 spindle bursts. Whereas
      direct stimulation of the cholinergic basal forebrain nuclei increased the
      occurrence probability of V1 spindle bursts, their chronic immunotoxic lesion
      using 192 IgG-saporin decreased the occurrence of neonatal V1 oscillatory
      activity by 87%. Thus, the cholinergic input facilitates the neonatal V1 spindle
      bursts and may prime the developing cortex to operate specifically on relevant
      early (retinal waves) and later (visual input) stimuli.

PMID- 17522313
TI  - Cholinergic axons modulate GABAergic signaling among hippocampal interneurons via
      postsynaptic alpha 7 nicotinic receptors.
AB  - Homopentameric alpha7 nicotinic receptors have a high affinity for acetylcholine
      (ACh), are permeable to Ca2+ ions, and are abundant in hippocampal interneurons.
      Although nicotinic agonists evoke inward currents and Ca2+ transients in stratum
      radiatum interneurons, the role of endogenous ACh in modulating synaptic
      integration by interneurons is incompletely understood. Many cholinergic axonal
      varicosities do not have postsynaptic specializations, but alpha7 receptors
      frequently occur close to synaptic GABA(A) receptors. These observations raise
      the possibility that alpha7 nicotinic receptors activated by ACh released from
      cholinergic axons modulate GABAergic transmission in interneurons. We show that
      agonists of alpha7 receptors profoundly depress GABAergic IPSCs recorded in
      stratum radiatum interneurons in the CA1 region of the hippocampus. This
      depression is accompanied by a small increase in GABA release. Alpha7 nicotinic
      receptor agonists also depress GABA- or muscimol-evoked currents in interneurons,
      indicating that the major effect is a postsynaptic modulation of GABA(A)
      receptors. The depression of GABA-evoked currents is abolished by chelating Ca2+
      in the recorded interneuron and attenuated by inhibitors of PKC. We also show
      that stimuli designed to release endogenous ACh from cholinergic axons evoke an
      alpha7 receptor-dependent heterosynaptic depression of GABAergic IPSCs in
      interneurons. This heterosynaptic modulation is amplified by blocking
      cholinesterases. These results reveal a novel mechanism by which cholinergic
      neurons modulate information processing in the hippocampus.

PMID- 17522315
TI  - A dynamic nonlinearity and spatial phase specificity in macaque V1 neurons.
AB  - While studying the visual response dynamics of neurons in the macaque primary
      visual cortex (V1), we found a nonlinearity of temporal response that influences
      the visual functions of V1 neurons. Simple cells were recorded in all layers of
      V1; the nonlinearity was strongest in neurons located in layer 2/3. We recorded
      the spike responses to optimal sinusoidal gratings that were displayed for 100
      ms, a temporal step response. The step responses were measured at many spatial
      phases of the grating stimulus. To judge whether simple cell behavior was
      consistent with linear temporal integration, the decay of the 100 ms step
      response at the preferred spatial phase was used to predict the step response at
      the opposite spatial phase. Responses in layers 4B and 4C were mostly consistent
      with a linear-plus-static-nonlinearity cascade model. However, this was not true
      in layer 2/3 where most cells had little or no step responses at the opposite
      spatial phase. Many layer 2/3 cells had transient preferred-phase responses but
      did not respond at the offset of the opposite-phase stimuli, indicating a dynamic
      nonlinearity. A different stimulus sequence, rapidly presented random sinusoids,
      also produced the same effect, with layer 2/3 simple cells exhibiting elevated
      spike rates in response to stimuli at one spatial phase but not 180 degrees away.
      The presence of a dynamic nonlinearity in the responses of V1 simple cells
      indicates that first-order analyses often capture only a fraction of neuronal
      behavior. The visual implication of our results is that simple cells in layer 2/3
      are spatial phase-sensitive detectors that respond to contrast boundaries of one
      sign but not the opposite.

PMID- 17522316
TI  - Apoptosis signal-regulating kinase 1 in amyloid beta peptide-induced cerebral
      endothelial cell apoptosis.
AB  - A pathological hallmark of Alzheimer's disease is accumulation of amyloid-beta
      peptide (Abeta) in senile plaques. Abeta has also been implicated in vascular
      degeneration in cerebral amyloid angiopathy because of its cytotoxic effects on
      non-neuronal cells, including cerebral endothelial cells (CECs). We explore the
      role of apoptosis signal-regulating kinase 1 (ASK1) in Abeta-induced death in
      primary cultures of murine CECs. Abeta induced ASK1 dephosphorylation, which
      could be prevented by selective inhibition of protein phosphatase 2A (PP2A) but
      not PP2B. ASK1 dephosphorylation resulted in its dissociation from 14-3-3. ASK1,
      released from 14-3-3 inhibition, activated p38 mitogen-activated protein kinase
      (p38MAPK), leading to p53 phosphorylation. p53, a proapoptotic transcription
      factor, in turn transactivated the expression of Bax, a proapoptotic protein.
      Transfection with various dominant-negative mutants (DNs), including ASK1 DN and
      p38MAPK DN, suppressed Abeta-induced p38MAPK activation, p53 phosphorylation, and
      Bax upregulation and partially prevented CEC death. Bax knockdown using a bax
      small interfering RNA strategy also reduced Bax expression and subsequent CEC
      death. These results suggest that Abeta activates the ASK1-p38MAPK-p53-Bax
      cascade to cause CEC death in a PP2A-dependent manner.

PMID- 17522317
TI  - Glutamatergic afferents of the ventral tegmental area in the rat.
AB  - Glutamatergic inputs to the ventral tegmental area (VTA), thought crucial to the
      capacity of the VTA to detect and signal stimulus salience, have been reported to
      arise in but a few structures. However, the afferent system of the VTA comprises
      very abundant neurons within a large formation extending from the prefrontal
      cortex to the caudal brainstem. Neurons in nearly all parts of this continuum may
      be glutamatergic and equivalently important to VTA function. Thus, we sought to
      identify the full range of glutamatergic inputs to the VTA by combining
      retrograde transport of wheat germ agglutinin-bound gold after injections into
      the VTA with nonisotopic in situ hybridization of the vesicular glutamate
      transporters (VGLUTs) 1, 2, and 3. We found glutamatergic neurons innervating the
      VTA in almost all structures projecting there and that a majority of these are
      subcortical and VGLUT2 mRNA positive. The tremendous convergence of glutamatergic
      afferents from many brain areas in the VTA suggests that (1) the function of the
      VTA requires integration of manifold and diverse bits of information and (2) the
      activity of the VTA reflects the ongoing activities of various combinations of
      its afferents.

PMID- 17522318
TI  - Optimal sensorimotor integration in recurrent cortical networks: a neural
      implementation of Kalman filters.
AB  - Several behavioral experiments suggest that the nervous system uses an internal
      model of the dynamics of the body to implement a close approximation to a Kalman
      filter. This filter can be used to perform a variety of tasks nearly optimally,
      such as predicting the sensory consequence of motor action, integrating sensory
      and body posture signals, and computing motor commands. We propose that the
      neural implementation of this Kalman filter involves recurrent basis function
      networks with attractor dynamics, a kind of architecture that can be readily
      mapped onto cortical circuits. In such networks, the tuning curves to variables
      such as arm velocity are remarkably noninvariant in the sense that the amplitude
      and width of the tuning curves of a given neuron can vary greatly depending on
      other variables such as the position of the arm or the reliability of the sensory
      feedback. This property could explain some puzzling properties of tuning curves
      in the motor and premotor cortex, and it leads to several new predictions.

PMID- 17522319
TI  - Striking variations in corticosteroid modulation of long-term potentiation along
      the septotemporal axis of the hippocampus.
AB  - The ability to express long-term potentiation (LTP) of reactivity to afferent
      stimulation along the septotemporal axis was explored in transverse rat
      hippocampal slices. The ventral pole of the hippocampus (VH) was found to be much
      impaired in ability to express LTP compared with the rest of the hippocampus. An
      exposure to acute stress before the rat was killed reversed this trend, and
      slices from VH now expressed a large LTP, whereas in the rest of the hippocampus,
      it was much suppressed. The enhanced LTP in VH was mediated by activation of a
      mineralocorticoid receptor (MR), whereas the suppressed LTP was mediated by
      activation of a glucocorticoid receptor, and indeed selective agonists of the
      respective steroid receptors mimicked the effects of stress, whereas selective
      antagonists blocked them. The MR-enhanced LTP in VH was not mediated by
      activation of the NMDA receptor but by enhancement of voltage-gated calcium
      channels. Because the VH has an unique efferent system to the hypothalamus, these
      results indicate that stress may activate this system while suppressing the
      ability of the rest of the hippocampus to express plastic properties under
      stressful conditions.

PMID- 17522320
TI  - NP031112, a thiadiazolidinone compound, prevents inflammation and
      neurodegeneration under excitotoxic conditions: potential therapeutic role in
      brain disorders.
AB  - Inflammation and neurodegeneration coexist in many acute damage and chronic CNS
      disorders (e.g., stroke, Alzheimer's disease, Parkinson's disease). A well
      characterized animal model of brain damage involves administration of kainic
      acid, which causes limbic seizure activity and subsequent neuronal death,
      especially in the CA1 and CA3 pyramidal cells and interneurons in the hilus of
      the hippocampus. Our previous work demonstrated a potent anti-inflammatory and
      neuroprotective effect of two thiadiazolidinones compounds, NP00111 (2,4-dibenzyl
      [1,2,4]thiadiazolidine-3,5-dione) and NP01138 (2-ethyl-4-phenyl
      [1,2,4]thiadiazolidine-3,5-dione), in primary cultures of cortical neurons,
      astrocytes, and microglia. Here, we show that injection of NP031112, a more
      potent thiadiazolidinone derivative, into the rat hippocampus dramatically
      reduces kainic acid-induced inflammation, as measured by edema formation using T2
      weighted magnetic resonance imaging and glial activation and has a
      neuroprotective effect in the damaged areas of the hippocampus. Last, NP031112
      induced neuroprotection, both in vitro and in vivo, was substantially attenuated
      by cotreatment with GW9662 (2-chloro-5-nitrobenzanilide), a known antagonist of
      the nuclear receptor peroxisome proliferator-activated receptor gamma, suggesting
      that the effects of NP031112 can be mediated through activation of this receptor.
      As such, these findings identify NP031112 as a potential therapeutic agent for
      the treatment of neurodegenerative disorders.

PMID- 17522321
TI  - The transduction channel TRPM5 is gated by intracellular calcium in taste cells.
AB  - Bitter, sweet, and umami tastants are detected by G-protein-coupled receptors
      that signal through a common second-messenger cascade involving gustducin,
      phospholipase C beta2, and the transient receptor potential M5 (TRPM5) ion
      channel. The mechanism by which phosphoinositide signaling activates TRPM5 has
      been studied in heterologous cell types with contradictory results. To resolve
      this issue and understand the role of TRPM5 in taste signaling, we took advantage
      of mice in which the TRPM5 promoter drives expression of green fluorescent
      protein and mice that carry a targeted deletion of the TRPM5 gene to
      unequivocally identify TRPM5-dependent currents in taste receptor cells. Our
      results show that brief elevation of intracellular inositol trisphosphate or Ca2+
      is sufficient to gate TRPM5-dependent currents in intact taste cells, but only
      intracellular Ca2+ is able to activate TRPM5-dependent currents in excised
      patches. Detailed study in excised patches showed that TRPM5 forms a nonselective
      cation channel that is half-activated by 8 microM Ca2+ and that desensitizes in
      response to prolonged exposure to intracellular Ca2+. In addition to channels
      encoded by the TRPM5 gene, we found that taste cells have a second type of Ca2+
      activated nonselective cation channel that is less sensitive to intracellular
      Ca2+. These data constrain proposed models for taste transduction and suggest a
      link between receptor signaling and membrane potential in taste cells.

PMID- 17522322
TI  - Disambiguation of overlapping experiences by neurons in the medial entorhinal
      cortex.
AB  - Hippocampal neuronal activity distinguishes separate events that share common
      elements. Here, we examined whether the capacity to disambiguate overlapping
      experiences is an exclusive feature of hippocampal processing or whether
      information processing one stage earlier in the hippocampal system also
      disambiguates common elements of distinct experiences. We compared the spatial
      firing patterns of neurons in the dorsocaudal medial entorhinal cortex (dcMEC)
      and hippocampal CA1 neurons in animals continuously alternating left-turn and
      right-turn routes through a T-maze. Neurons in the dcMEC more strongly
      distinguished left-turn from right-turn trials compared with CA1 neurons, whereas
      CA1 neurons more selectivity encoded places traversed within each route. These
      results indicate that dcMEC spatial firing patterns are experience dependent and
      reflect the mnemonic demands of a spatial memory task. Furthermore, the results
      suggest that neuronal populations in the dcMEC and CA1 differentially emphasize
      complementary aspects of spatial memory representations.

PMID- 17522323
TI  - Time discounting for primary rewards.
AB  - Previous research, involving monetary rewards, found that limbic reward-related
      areas show greater activity when an intertemporal choice includes an immediate
      reward than when the options include only delayed rewards. In contrast, the
      lateral prefrontal and parietal cortex (areas commonly associated with
      deliberative cognitive processes, including future planning) respond to
      intertemporal choices in general but do not exhibit sensitivity to immediacy
      (McClure et al., 2004). The current experiments extend these findings to primary
      rewards (fruit juice or water) and time delays of minutes instead of weeks.
      Thirsty subjects choose between small volumes of drinks delivered at precise
      times during the experiment (e.g., 2 ml now vs 3 ml in 5 min). Consistent with
      previous findings, limbic activation was greater for choices between an immediate
      reward and a delayed reward than for choices between two delayed rewards, whereas
      the lateral prefrontal cortex and posterior parietal cortex responded similarly
      whether choices were between an immediate and a delayed reward or between two
      delayed rewards. Moreover, relative activation of the two sets of brain regions
      predicts actual choice behavior. A second experiment finds that when the delivery
      of all rewards is offset by 10 min (so that the earliest available juice reward
      in any choice is 10 min), no differential activity is observed in limbic reward
      related areas for choices involving the earliest versus only more delayed
      rewards. We discuss implications of this finding for differences between primary
      and secondary rewards.

PMID- 17522324
TI  - Unconscious activation of the cognitive control system in the human prefrontal
      cortex.
AB  - Using functional magnetic resonance imaging, we tested whether unconscious
      information can influence the cognitive control system in the human prefrontal
      cortex. Volunteers had to prepare to perform either a phonological judgment or a
      semantic judgment on an upcoming word, based on the instruction given at the
      beginning of each trial. However, in some trials they were visually primed to
      prepare for the alternative (i.e., "wrong") task, and this impaired their
      performance. This priming effect is taken to depend on unconscious processes
      because the effect was present even when the volunteers could only discriminate
      the identity of the primes at chance level. Furthermore, the effect was stronger
      when the visibility of the prime was near zero than when the visibility of the
      prime was significantly higher. When volunteers were unconsciously primed to
      perform the alternative task, there was also decreased neural activity in the
      brain areas relevant to the instructed task and increased neural activity in the
      brain areas relevant to the alternative task, which shows that the volunteers
      were actually engaged in the wrong task, instead of simply being distracted.
      Activity in the mid-dorsolateral prefrontal cortex was also found to be
      associated with this unconscious priming effect. These results suggest that the
      cognitive control system in the prefrontal cortex is not exclusively driven by
      conscious information, as has been believed previously.

PMID- 17522325
TI  - Endogenous TrkB ligands suppress functional mechanosensory plasticity in the
      deafferented spinal cord.
AB  - Dorsal root injury (DRI) disrupts the flow of sensory information to the spinal
      cord. Although primary afferents do not regenerate to their original targets,
      spontaneous recovery can, by unknown mechanisms, occur after DRI. Here, we show
      that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not
      nerve growth factor or neurotrophin-4, are upregulated in the spinal gray matter
      after DRI. Because endogenous BDNF and NT-3 have well established roles in
      synaptic and axonal plasticity, we hypothesized that they contributed to
      spontaneous recovery after DRI. We first developed a model of DRI-induced
      mechanosensory dysfunction: rat C7/8 DRI produced a deficit in low-threshold
      cutaneous mechanosensation that spontaneously improved within 10 d but did not
      recover completely. To determine the effects of endogenous BDNF and NT-3, we
      administered TrkB-Fc or TrkC-Fc fusion proteins throughout the recovery period.
      To our surprise, TrkB-Fc stimulated complete recovery of mechanosensation by 6 d
      after DRI. It also stimulated mechanosensory axon sprouting but prevented
      deafferentation-induced serotonergic sprouting. TrkC-Fc had no effect on low
      threshold mechanosensory behavior or axonal plasticity. There was no
      mechanosensory improvement with single-bolus TrkB-Fc infusions at 10 d after DRI
      (despite significantly reducing rhizotomy-induced cold pain), indicating that
      neuromodulatory effects of BDNF did not underlie mechanosensory recovery.
      Continuous infusion of the pan-neurotrophin antagonist K252a also stimulated
      behavioral and anatomical plasticity, indicating that these effects of TrkB-Fc
      treatment occurred independent of signaling by other neurotrophins. These results
      illustrate a novel, plasticity-suppressing effect of endogenous TrkB ligands on
      mechanosensation and mechanosensory primary afferent axons after spinal
      deafferentation.

PMID- 17522326
TI  - Cytoplasmic dynein and LIS1 are required for microtubule advance during growth
      cone remodeling and fast axonal outgrowth.
AB  - Recent evidence has implicated dynein and its regulatory factors dynactin and
      LIS1 in neuronal and non-neuronal cell migration. In the current study we sought
      to test whether effects on neuronal cell motility might reflect, in part, a role
      for these proteins in the growth cone. In chick sensory neurons subjected to
      acute laminin treatment dynein, dynactin, and LIS1 were mobilized strikingly and
      rapidly to the leading edge of the growth cone, where they were seen to be
      associated with microtubules converging into the laminin-induced axonal
      outgrowths. To interfere acutely with LIS1 and dynein function and to minimize
      secondary phenotypic effects, we injected antibodies to these proteins just
      before axon initiation. Antibody to both proteins produced an almost complete
      block of laminin-induced growth cone remodeling and the underlying reorganization
      of microtubules. Penetration of microtubules into the peripheral zone of
      differentiating axonal growth cones was decreased dramatically by antibody
      injection, as judged by live analysis of enhanced green fluorescent protein
      tubulin and the microtubule tip-associated EB3 (end-binding protein 3). Dynein
      and LIS1 inhibition had no detectable effect on microtubule assembly but reduced
      the ability of microtubules to resist retrograde actin flow. In hippocampal
      neurons dynein, dynactin, and LIS1 were enriched in axonal growth cones at stage
      3, and both growth cone organization and axon elongation were altered by LIS1 RNA
      interference. Together, our data indicate that dynein and LIS1 play a
      surprisingly prominent role in microtubule advance during growth cone remodeling
      associated with axonogenesis. These data may explain, in part, the role of these
      proteins in brain developmental disease and support an important role in diverse
      aspects of neuronal differentiation and nervous system development.

PMID- 17522327
TI  - Evaluation of serological tests to identify Trypanosoma cruzi infection in humans
      and determine cross-reactivity with Trypanosoma rangeli and Leishmania spp.
AB  - Five commercially available enzyme-linked immunosorbent assays (ELISAs), one in
      house ELISA, and two hemagglutination assays were evaluated to determine their
      diagnostic accuracy for Chagas' disease in two studies. In study 1, ELISA kits
      showed 100% sensitivity, but specificities ranged from 82.84% to 100% when
      leishmaniasis cases were included and from 95.57% to 100% when leishmaniasis
      cases were excluded. Kits using recombinant antigens or synthetic peptides are
      more specific than those using crude extracts from Trypanosoma cruzi epimastigote
      forms. Kits evaluated in Panama, in study 2, showed 75% to 100% sensitivity and
      97.12% to 100% specificity. These data were obtained by using a Western blot
      assay with T. cruzi trypomastigote excreted-secreted antigens as a reference test
      to confirm T. cruzi infection.

PMID- 17522328
TI  - Enhanced ex vivo stimulation of Mycobacterium tuberculosis-specific T cells in
      human immunodeficiency virus-infected persons via antigen delivery by the
      Bordetella pertussis adenylate cyclase vector.
AB  - The genetically detoxified Bordetella pertussis adenylate cyclase is a promising
      delivery system for immunodominant tuberculosis antigens in gamma interferon
      release assays. This system has not been evaluated in human immunodeficiency
      virus (HIV)-infected persons in high tuberculosis prevalence areas. A whole-blood
      gamma interferon release assay with Mycobacterium tuberculosis antigens (early
      secreted antigenic target 6, culture filtrate protein 10, alpha-crystallin 2, and
      TB10.3) delivered by adenylate cyclase in addition to native tuberculosis
      antigens (without adenylate cyclase delivery) was evaluated in 119 adults in
      Khayelitsha Township, Cape Town, South Africa. Results were compared to
      tuberculin skin test results of 41 HIV-positive and 42 HIV-negative asymptomatic
      persons, in addition to 36 HIV-positive persons with recently diagnosed smear- or
      culture-positive pulmonary tuberculosis. Delivery of tuberculosis antigens by
      adenylate cyclase decreased by 10-fold the amount of antigen required to
      restimulate T cells. Furthermore, the responses of HIV-positive persons with a
      low response to native tuberculosis antigens were enhanced when these antigens
      were delivered by adenylate cyclase. When gamma interferon responses to the
      tuberculosis antigens (with or without delivery by adenylate cyclase) were
      combined, a significantly higher number of patients were scored positive than by
      tuberculin skin testing. Ex vivo responses to tuberculosis antigens delivered by
      adenylate cyclase are maintained in the context of HIV infection. Our findings
      suggest that the majority of those in this population are infected with
      tuberculosis, which is of significant public health importance.

PMID- 17522329
TI  - Diffusion and perfusion imaging in subacute neurotoxicity following high-dose
      intravenous methotrexate.
AB  - Methotrexate (MTX) is a widely used chemotherapeutic agent that can cause acute,
      subacute, and chronic neurological complications. Subacute MTX neurotoxicity is
      manifest by abrupt onset of focal cerebral dysfunction occurring days to weeks
      after MTX administration, usually in children. We describe the neuroimaging
      features of an adult patient with primary CNS lymphoma who presented with
      transient aphasia and right hemiparesis 12 days after receiving intravenous high
      dose MTX (8 g/m2) chemotherapy. Imaging within 1 h of symptom onset showed
      bilateral symmetrical restricted diffusion involving white matter of the cerebral
      hemispheres. CT angiogram and dynamic susceptibility MRI showed no evidence of
      vasospasm or perfusion defect. MRI five days later showed near-complete
      resolution of the abnormalities. MRI 3(1/2) months later showed normal diffusion
      but new hyperintense T2-weighted signal changes in the subcortical white matter
      corresponding to previous areas of restricted diffusion. The absence of vascular
      or perfusion abnormalities suggests that transient cytotoxic edema in white
      matter may explain the syndrome of subacute MTX neurotoxicity.

PMID- 17522330
TI  - Inhibiting TGF-beta signaling restores immune surveillance in the SMA-560 glioma
      model.
AB  - Transforming growth factor-beta (TGF-beta) is a proinvasive and immunosuppressive
      cytokine that plays a major role in the malignant phenotype of gliomas. One novel
      strategy of disabling TGF-beta activity in gliomas is to disrupt the signaling
      cascade at the level of the TGF-beta receptor I (TGF-betaRI) kinase, thus
      abrogating TGF-beta-mediated invasiveness and immune suppression. SX-007, an
      orally active, small-molecule TGF-betaRI kinase inhibitor, was evaluated for its
      therapeutic potential in cell culture and in an in vivo glioma model. The
      syngeneic, orthotopic glioma model SMA-560 was used to evaluate the efficacy of
      SX-007. Cells were implanted into the striatum of VM/Dk mice. Dosing began three
      days after implantation and continued until the end of the study. Efficacy was
      established by assessing survival benefit. SX-007 dosed at 20 mg/kg p.o. once
      daily (q.d.) modulated TGF-beta signaling in the tumor and improved the median
      survival. Strikingly, approximately 25% of the treated animals were disease-free
      at the end of the study. Increasing the dose to 40 mg/kg q.d. or 20 mg/kg twice
      daily did not further improve efficacy. The data suggest that SX-007 can exert a
      therapeutic effect by reducing TGF-beta-mediated invasion and reversing immune
      suppression. SX-007 modulates the TGF-beta signaling pathway and is associated
      with improved survival in this glioma model. Survival benefit is due to reduced
      tumor invasion and reversal of TGF-beta-mediated immune suppression, allowing for
      rejection of the tumor. Together, these results suggest that treatment with a TGF
      betaRI inhibitor may be useful in the treatment of glioblastoma.

PMID- 17522331
TI  - Gene delivery into malignant glioma by infectivity-enhanced adenovirus: in vivo
      versus in vitro models.
AB  - Adenoviral (Ad) vectors demonstrate several attributes of potential utility for
      glioma gene therapy. Although Ad infection is limited in vitro by low expression
      levels of the coxsackie-adenoviral receptor (CAR), in vivo studies have shown the
      efficacy of Ad vectors as gene delivery vectors. To evaluate the in vivo utility
      of CAR-independent, infectivity-enhanced Ad vectors, we employed genetically
      modified Ad vectors in several experimental models of human gliomas. We used
      three capsid-modified Ad vectors: (1) a chimeric Ad vector with a human Ad
      backbone and a fiber knob of a canine Ad, (2) an Ad vector with a polylysine
      motif incorporated into the fiber gene, and (3) a double-modified Ad vector
      incorporating both an RGD4C peptide and the polylysine motif. These three
      modified Ad vectors target, respectively, the putative membrane receptor(s) of
      the canine Ad vector, heparan sulfate proteoglycans (HSPGs), and both integrins
      and HSPGs. Our in vitro studies indicated that these retargeting strategies all
      enhanced CAR-independent infectivity in both established and primary low-passage
      glioma cells. Enhancement of in vitro gene delivery by the capsid-modified
      vectors correlated inversely with the levels of cellular CAR expression. However,
      in vivo in orthotopic human glioma xenografts, the unmodified Ad vector was not
      inferior relative to the capsid-modified Ad vector. Although genetic strategies
      to circumvent CAR deficiency in glioma cells could reproducibly expand the
      cellular entry mechanisms of Ad vectors in cultured and primary glioma cells,
      these approaches were insufficient to confer in vivo significant infectivity
      enhancement over unmodified Ad vectors. Other factors, probably the extracellular
      matrix, stromal cells, and the three-dimensional tumor architecture, clearly play
      important roles in vivo and interfere with Ad-based gene delivery into glioma
      tumors.

PMID- 17522332
TI  - Expression of the neurogenic basic helix-loop-helix transcription factor NEUROG1
      identifies a subgroup of medulloblastomas not expressing ATOH1.
AB  - To gain insight into the lineage of origin of medulloblastomas, the mRNA
      expression of NEUROG1, a gene encoding a proneural transcription factor
      transiently detected during nervous system development, was investigated in 27
      human medulloblastomas characterized for mRNA expression of ATOH1, a marker of
      cerebellar granule precursors and corresponding medulloblastomas. Expression of
      Ngn1, the mouse homolog of NEUROG1, was also analyzed in the mouse cerebellar
      primordium. In addition, we studied mRNA expression of GLI1 as a marker of the
      SHH pathway activation, and nuclear beta-catenin staining, beta-catenin
      mutations, and mRNA expression of MYC as indicators of the WNT pathway status. In
      15 cases, we also examined expression of OTX2, a transcription factor recently
      indicated as a positive marker of medulloblastomas originating from cerebellar
      granule precursors. The mRNA expression of NEUROG1 and Ngn1 was selectively found
      in medulloblastomas not expressing ATOH1 and in progenitors of the cerebellar
      ventricular zone, respectively. GLI1 transcript was expressed in medulloblastomas
      with ATOH1 transcript, whereas high levels of MYC transcript were unrelated to
      NEUROG1 or ATOH1 expression. No clear association between MYC overexpression and
      nuclear beta-catenin staining was found. Finally, OTX2 mRNA was expressed in all
      medulloblastomas with NEUROG1 transcript, but also in a subset of these
      malignancies with ATOH1 transcript. These observations may help to define the
      lineage of origin of medulloblastomas, and support a role for ATOH1 and NEUROG1
      in the classification of these malignancies.

PMID- 17522333
TI  - Incidence of gliomas by anatomic location.
AB  - The anatomic location of a glioma influences prognosis and treatment options. The
      aim of our study was to describe the distribution of gliomas in different
      anatomic areas of the brain. A representative population-based sample of 331
      adults with glioma was used for preliminary analyses. The anatomic locations for
      89 patients from a single center were analyzed in more detail from radiologic
      imaging and recorded on a three-dimensional 1 x 1 x 1-cm grid. The age
      standardized incidence rate of gliomas was 4.7 per 100,000 person-years. The most
      frequent subtypes were glioblastoma (47%) and grade II-III astrocytoma (23%),
      followed by oligodendroglioma and mixed glioma. The gliomas were located in the
      frontal lobe in 40% of the cases, temporal in 29%, parietal in 14%, and occipital
      lobe in 3%, with 14% in the deeper structures. The difference in distribution
      between lobes remained after adjustment for their tissue volume: the tumor:volume
      ratio was 4.5 for frontal, 4.8 for temporal, and 2.3 for parietal relative to the
      occipital lobe. The area with the densest occurrence was the anterior subcortical
      brain. Statistically significant spatial clustering was found in the three
      dimensional analysis. No differences in location were found among glioblastoma,
      diffuse astrocytoma, and oligodendroglioma. Our results demonstrate considerable
      heterogeneity in the anatomic distribution of gliomas within the brain.

PMID- 17522334
TI  - Activity of VNP40101M (Cloretazine) in the treatment of CNS tumor xenografts in
      athymic mice.
AB  - VNP40101M, or 1,2-bis(methylsulfonyl)-1-(2-choloroethyl)-2
      (methylamino)carbonylhydrazine (Cloretazine), is a bifunctional prodrug that
      belongs to a class of DNA-modifying agents-the sulfonylhydrazines-that has been
      synthesized and been shown to have activity against a wide spectrum of
      xenografts. The current study was designed to assess the activity of VNP40101M
      administered at a dose of 18 mg/kg daily for five days against a panel of human
      adult and pediatric CNS tumors growing subcutaneously or intracranially in
      athymic nude mice. The results demonstrated statistically significant (p < 0.05)
      growth delays of 15.0, 8.3, 51.0, 60+, 60+, and 60+ days in subcutaneous
      xenografts derived from childhood glioblastoma multiforme (D-456 MG), childhood
      ependymoma (D-528 EP and D-612 EP), childhood medulloblastoma (D-425 MED), and
      adult malignant glioma (D-245 MG and D-54 MG), respectively, with corresponding
      tumor regressions in 10 of 10, 4 of 10, 8 of 10, 9 of 10, 9 of 10, and 10 of 10
      treated mice, respectively. Delayed toxicity was seen more than 60 days after
      treatment, with 23 deaths in 100 treated animals, despite a median weight loss of
      only 0.06%. In mice bearing intracranial D-245 MG xenografts, treatment with
      VNP40101M at a dose of 18 mg/kg daily for five days produced a 50% increase in
      median survival compared with controls. Additional experiments conducted against
      subcutaneous D-245 MG xenografts by using reduced doses of 13.5 or 9.0 mg/kg
      daily for five days demonstrated tumor growth delays of 82.2 and 53.5 days, with
      corresponding tumor regressions in 8 of 9 and 9 of 10 treated mice, respectively
      (all values, p < 0.001), with one toxic death. These findings suggest that
      VNP40101M is active in the treatment of a wide range of human central nervous
      system tumors and warrants translation to the clinic.

PMID- 17522336
TI  - EBV-associated lymphoproliferative disorder of CNS associated with the use of
      mycophenolate mofetil.
AB  - Epstein-Barr virus (EBV)-associated lymphoid proliferations are a well-recognized
      complication of congenital or acquired systemic immunosuppression. The CNS is a
      frequent site for development of such lymphoid proliferations. We describe the
      clinical, imaging, and pathologic observations of a CNS disorder histologically
      similar to posttransplantation lymphoproliferative disorder that occurred in four
      patients with autoimmune disease treated with mycophenolate mofetil (MM). Two
      patients had polymorphous lymphoplasmacytic infiltration of brain parenchyma, and
      two had monomorphous infiltrations consistent with diffuse large B-cell lymphoma.
      In situ hybridization for EBV-encoded RNA was positive in all four patients. All
      patients improved after MM withdrawal and the use of rituximab. Because of a
      favorable toxicity profile, MM is now being used as steroid-sparing
      immunomodulatory therapy in autoimmune disorders. Based on our experience
      presented herein, we recommend caution in patient selection for MM and strict
      surveillance of those patients with autoimmune disorders who receive MM.

PMID- 17522335
TI  - Optimization of adenoviral vector-mediated transgene expression in the canine
      brain in vivo, and in canine glioma cells in vitro.
AB  - Expression of the immune-stimulatory molecule Fms-like tyrosine kinase 3 ligand
      (Flt3L) and the conditional cytotoxic enzyme herpes simplex virus type 1
      thymidine kinase (HSV1-TK) provides long-term immune-mediated survival of large
      glioblastoma multiforme (GBM) models in rodents. A limitation for predictive
      testing of novel antiglioma therapies has been the lack of a glioma model in a
      large animal. Dogs bearing spontaneous GBM may constitute an attractive large
      animal model for GBM, which so far has remained underappreciated. In preparation
      for a clinical trial in dogs bearing spontaneous GBMs, we tested and optimized
      adenovirus-mediated transgene expression with negligible toxicity in the dog
      brain in vivo and in canine J3T glioma cells. Expression of the marker gene beta
      galactosidase (beta-Gal) was higher when driven by the murine (m) than the human
      (h) cytomegalovirus (CMV) promoter in the dog brain in vivo, without enhanced
      inflammation. In the canine brain, beta-Gal was expressed mostly in astrocytes.
      beta-Gal activity in J3T cells was also higher with the mCMV than the hCMV
      promoter driving tetracycline-dependent (TetON) transgene expression within high
      capacity adenovirus vectors (HC-Ads). Dog glioma cells were efficiently
      transduced by HC-Ads expressing mCMV-driven HSV1-TK, which induced 90% reduction
      in cell viability in the presence of ganciclovir. J3T cells were also effectively
      transduced with HC-Ads expressing Flt3L under the control of the regulatable
      TetON promoter system, and as predicted, Flt3L release was stringently inducer
      dependent. HC-Ads encoding therapeutic transgenes under the control of regulatory
      sequences driven by the mCMV promoter are excellent vectors for the treatment of
      spontaneous GBM in dogs, which constitute an ideal preclinical animal model.

PMID- 17522337
TI  - Case study of intracerebral plasmacytoma as an initial presentation of multiple
      myeloma.
AB  - Cerebral involvement is an uncommon complication of multiple myeloma. We report
      on a 64-year-old man hospitalized for a partial seizure. MRI showed two
      intracerebral lesions, which proved to be plasmacytomas. After complete staging,
      we retained the diagnosis of immunoglobulin G lambda-type multiple myeloma with
      CNS involvement. Cytogenetic analysis of plasma cells detected a deletion in the
      p53 gene at 17p13.1. Despite cranial radiotherapy and systemic chemotherapy, the
      patient's disease progressed rapidly and he died five months after diagnosis.
      What makes this case unusual is that overt multiple myeloma had been absent
      before cerebral involvement was discovered. It confirms the extremely poor
      prognosis of patients with CNS myeloma even in the presence of aggressive
      treatment. Cytogenetic abnormalities could be a marker of chromosomal and genetic
      instability, conferring to multiple myeloma a more aggressive profile.

PMID- 17522338
TI  - Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs
      independently of IFNgammaR1 signaling and IDO expression.
AB  - Multipotent mesenchymal stromal cells (MSCs) inhibit proliferation, helper, and
      effector functions in most if not all peripheral blood mononuclear cell (PBMC)
      subpopulations in vitro. The molecular mechanism is widely thought to imply
      tryptophan degradation by the interferon-gamma (IFNgamma)-induced expression of
      indoleamine 2,3-dioxygenase (IDO). However, IDO inhibitors were not able to
      restore proliferation of PBMCs in each case. Moreover, human MSCs with an
      IFNgamma receptor 1 (R1) defect inhibited proliferation of HLA-mismatched PBMCs
      to a similar extent as control MSCs. In contrast to healthy MSCs, IFNgammaR1
      deficient MSCs showed no detectable mRNA for IDO-neither in the absence nor in
      the presence of recombinant human IFNgamma, nor in coculture with HLA-mismatched
      PBMCs. Based on gene expression profiling, we were able to show that insulin-like
      growth factor (IGF)-binding proteins contribute to the inhibitory mechanism of
      MSCs. Taken together, human MSCs exert important immunomodulatory functions in
      the absence of IFNgammaR1 signaling and IDO, partially accounted for by IGF
      binding proteins.

PMID- 17522339
TI  - Isolated high-molecular-weight kininogen deficiency: a novel frameshift mutation
      in exon 10.

PMID- 17522340
TI  - Donor lymphocyte infusions for the treatment of minimal residual disease in acute
      leukemia.

PMID- 17522341
TI  - Killer cell Ig-like receptors CD158a and CD158b display a coactivatory function,
      involving the c-Jun NH2-terminal protein kinase signaling pathway, when expressed
      on malignant CD4+ T cells from a patient with Sezary syndrome.

PMID- 17522342
TI  - Impaired microsomal oxidation of the atypical antipsychotic agent clozapine in
      hepatic steatosis.
AB  - Hepatic lipid infiltration (steatosis) is a complication of the metabolic
      syndrome and can progress to nonalcoholic steatohepatitis and severe liver
      injury. Microsomal cytochrome P450 (P450) drug oxidases are down-regulated in
      experimental steatosis. In this study we evaluated the separate and combined
      effects of lipid accumulation and P450 down-regulation on the microsomal
      oxidation of the antipsychotic agent clozapine (CLZ), the use of which is
      associated with an increased incidence of the metabolic syndrome. Several
      important drug oxidizing P450s were down-regulated, and the formation of N
      desmethyl-CLZ (norCLZ) and CLZ N-oxide was decreased in microsomal fractions from
      orotic acid-induced early steatotic rat liver. Inclusion of lipids extracted from
      steatotic, but not control, liver decreased the free concentration of CLZ in
      microsomes and suppressed norCLZ formation; CLZ N-oxidation was unchanged.
      Triglycerides increased in steatotic liver to 15-fold of control, whereas
      increases in the monounsaturated oleic acid to 10-fold of control and total
      polyunsaturated and saturated fatty acids to 4- and 5-fold of control also
      occurred. Addition of triglycerides containing esterified omega-6 and omega-3
      fatty acids inhibited the microsomal formation of norCLZ but not that of CLZ N
      oxide; triglycerides esterified with unsaturated and monounsaturated fatty acids
      were inactive. Thus, drug oxidation may be suppressed in steatosis by P450 down
      regulation and the accumulation of polyunsaturated fatty esters. In contrast, the
      activity of the flavin-containing monooxygenase that mediates CLZ N-oxidation was
      unimpaired. Lipid deposition in livers of patients with the metabolic syndrome
      may necessitate dosage adjustments for toxic drugs, including CLZ.

PMID- 17522343
TI  - Antigen-specific suppression of experimental autoimmune encephalomyelitis by a
      novel bifunctional peptide inhibitor.
AB  - The objective of this study is to evaluate the activity of a novel peptide, i.e.,
      bifunctional peptide inhibitor (BPI), which targets the immunological synapse and
      inhibits autoimmune responses in an antigen-specific manner. Proteolipid protein
      (PLP)-BPI was designed by conjugating two peptides, an encephalitogenic epitope
      of proteolipid protein (PLP(139-151)) and an intercellular adhesion molecule-1
      binding peptide derived from alpha(L) integrin (CD11a(237-246)), via a spacer
      peptide. The therapeutic effect of PLP-BPI was studied in experimental autoimmune
      encephalomyelitis (EAE) in female SJL/J mice as a model for human multiple
      sclerosis. Mice that received i.v. injections of PLP-BPI showed significantly
      lower EAE disease scores and incidence than those treated with vehicle, PLP(139
      151) peptide only, CD11a(237-246) peptide only, unlinked mixture of PLP(139-151),
      and CD11a(237-246) peptides, or other control peptides. Multiple injections of
      antigenic peptide can produce anaphylactic responses; interestingly, PLP-BPI
      treated animals have significantly lower anaphylactic response than do the
      PLP(139-151)-treated group. Therefore, PLP-BPI can effectively inhibit the
      disease severity and incidence of EAE with a lower possibility of inducing fatal
      anaphylaxis. These results suggest that BPI-type molecules can be used to treat
      different autoimmune diseases in which antigenic epitopes have been identified.

PMID- 17522344
TI  - Iptakalim, a vascular ATP-sensitive potassium (KATP) channel opener, closes rat
      pancreatic beta-cell KATP channels and increases insulin release.
AB  - Sulfonylureas have been the leading oral antihyperglycemic agents, and they
      presently continue to be the most popular antidiabetic drugs prescribed for
      treatment of type 2 diabetes. However, concern has arisen over the side effects
      of sulfonylureas on the cardiovascular system. Here, we tested the hypothesis
      that iptakalim, a novel vascular ATP-sensitive potassium (K(ATP)) channel opener,
      closes rat pancreatic beta-cell K(ATP) channels and increases insulin release.
      Rat pancreatic beta-cell K(ATP) channels and heterologously expressed K(ATP)
      channels in both human embryonic kidney (HEK) 293 cells and Xenopus oocytes were
      used to test the pharmacological effects of iptakalim. Patch-clamp recordings,
      Ca(2+) imaging, and measurements of insulin release were applied. Patch-clamp
      whole-cell recordings revealed that iptakalim depolarized beta-cells, induced
      action potential firing, and reduced K(ATP) channel-mediated currents. Single
      channel recordings revealed that iptakalim reduced the open probability of K(ATP)
      channels without changing channel sensitivity to ATP. By closing beta-cell K(ATP)
      channels, iptakalim elevated intracellular Ca(2+) concentrations and increased
      insulin release. In addition, iptakalim decreased the open probability of
      recombinant Kir6.2FL4A (a trafficking mutant of the Kir6.2) K(ATP) channels
      heterologously expressed in HEK 293 cells, suggesting that iptakalim suppressed
      the function of beta-cell K(ATP) channels by directly inhibiting the Kir6.2
      subunit. Finally, iptakalim inhibited Kir6.2/SUR1, but it activated Kir6.1/SUR2B
      (vascular-type), K(ATP) channels heterologously expressed in Xenopus oocytes.
      Iptakalim bidirectionally regulated pancreatic-type and vascular-type K(ATP)
      channels, and this unique pharmacological property suggests the potential use of
      iptakalim as a new therapeutic strategy for treating type 2 diabetes with the
      additional benefit of alleviating vascular disorders.

PMID- 17522345
TI  - Atrial natriuretic peptide reduces ischemia/reperfusion-induced spinal cord
      injury in rats by enhancing sensory neuron activation.
AB  - We recently demonstrated that calcitonin gene-related peptide (CGRP) released
      from sensory neurons reduces spinal cord injury (SCI) by inhibiting neutrophil
      activation through an increase in the endothelial production of prostacyclin
      (PGI(2)). Carperitide, a synthetic alpha-human atrial natriuretic peptide (ANP),
      reduces ischemia/reperfusion (I/R)-induced tissue injury. However, its precise
      therapeutic mechanism(s) remains to be elucidated. In the present study, we
      examined whether ANP reduces I/R-induced spinal cord injury by enhancing sensory
      neuron activation using rats. ANP increased CGRP release and cellular cAMP levels
      in dorsal root ganglion neurons isolated from rats in vitro. The increase in CGRP
      release induced by ANP was reversed by pretreatment with capsazepine, an
      inhibitor of vanilloid receptor-1 activation, or with (9S, 10S, 12R)
      2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3
      fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]-benzodiazocine-10-carboxylic acid hexyl ester
      (KT5720), an inhibitor of protein kinase A (PKA), suggesting that ANP might
      increase CGRP release from sensory neurons by activating PKA through an increase
      in the cellular cAMP level. Spinal cord ischemia was induced in rats using a
      balloon catheter placed in the aorta. ANP reduced mortality and motor
      disturbances by inhibiting reduction of the number of motor neurons in animals
      subjected to SCI. ANP significantly enhanced I/R-induced increases in spinal cord
      tissue levels of CGRP and 6-keto-prostaglandin F(1alpha). a stable metabolite of
      PGI(2). ANP inhibited I/R-induced increases in spinal cord tissue levels of tumor
      necrosis factor and myeloperoxidase. Pretreatment with 4'-chloro-3
      methoxycinnamanilide (SB366791), a specific vanilloid receptor-1 antagonist, and
      indomethacin reversed the effects of ANP. These results strongly suggest that ANP
      might reduce I/R-induced SCI in rats by inhibiting neutrophil activation through
      enhancement of sensory neuron activation.

PMID- 17522346
TI  - Technology assessment in radiology: putting the evidence in evidence-based
      radiology.
AB  - In this review, which is part of a larger series on evidence-based practice in
      radiology, the relationship between technology assessment (TA) and the practice
      of evidence-based radiology (EBR) is discussed. TA guides researchers in the
      methods required to be reliable providers of unbiased and relevant evidence.
      Meanwhile, EBR equips radiologists with the skills needed to be discerning
      consumers of that evidence. Both paradigms aim to improve the effectiveness of
      health care spending. In this review, it is argued that EBR can be only as good
      as the TA on which it is based. However, TA is particularly complex in regard to
      diagnostic radiology because of the many links in the chain between the interim
      objective (to make the correct diagnosis) and the ultimate goal (to improve
      patient health). In this article, the development of TA in medicine in general
      and, more specifically, the TA hierarchy for the evaluation of diagnostic imaging
      are described. Some of the improvements in the pool of evidence during the past
      30 years are documented, and some of the remaining tensions between TA and EBR
      are highlighted.

PMID- 17522347
TI  - Relapsing neuromyelitis optica and relapsing-remitting multiple sclerosis:
      differentiation at diffusion-tensor MR imaging of corpus callosum.
AB  - PURPOSE: To prospectively assess sensitivity and specificity of diffusion indexes
      of the corpus callosum (CC) for differentiating relapsing neuromyelitis optica
      (RNMO) from relapsing-remitting multiple sclerosis (RRMS), by using final
      clinical diagnosis as the reference standard. MATERIALS AND METHODS: Participants
      provided informed consent; the study was approved by the institutional review
      board. Forty-six consecutive patients with RRMS (18 men, 28 women; mean age, 37.7
      years; range, 18-58 years) and 26 consecutive patients with RNMO (two men, 24
      women; mean age, 38.6 years; range, 19-59 years) underwent diffusion-tensor
      magnetic resonance imaging. Mean diffusivity (MD) and fractional anisotropy (FA)
      of the region of interest (ROI) of the CC in the midsagittal plane were measured
      and used as discriminative indexes. Bayesian classification with leave-one-out
      cross-validation was used to determine diagnostic accuracy. Differences in
      diffusion indexes of ROIs among groups were evaluated by using the Kruskal-Wallis
      test, followed by the Mann-Whitney U test for multiple comparisons and Bonferroni
      correction. RESULTS: Mean MD (8.48 x 10(-4) mm(2)/sec) and FA (0.729) of the ROI
      in patients with RNMO were significantly (P<.001) different from those (MD=10.64
      x 10(-4) mm(2)/sec, FA=0.599) in patients with RRMS. Sensitivity and specificity
      for differentiation were 92.3% (24 of 26 patients with RNMO) and 93.5% (43 of 46
      patients with RRMS) for FA and 88.5% (23 of 26 patients with RNMO) and 89.1% (41
      of 46 patients with RRMS) for MD, respectively. CONCLUSION: Measurement of
      diffusion indexes of the CC may be useful for distinguishing patients with RNMO
      from those with RRMS.

PMID- 17522348
TI  - Detection of simulated microcalcifications in a phantom with digital mammography:
      effect of pixel size.
AB  - PURPOSE: To evaluate the effect of pixel size on the detection of simulated
      microcalcifications in a phantom with digital mammography. MATERIALS AND METHODS:
      A high-spatial-resolution prototype imager that yields variable pixel size (39
      and 78 microm) and a clinical full-field digital mammography (FFDM) system that
      yields a 100-microm pixel size were used. Radiographic images of a contrast
      detail (CD) phantom were obtained to perform four-alternative forced-choice
      observer experiments. Polymethylmethacrylate was added to obtain phantom
      thicknesses of 45 and 58 mm, which are typical breast thicknesses encountered in
      mammography. Phantom images were acquired with both systems under nearly
      identical exposure conditions by using an antiscatter grid. Twelve images were
      acquired for each phantom thickness and pixel size (for a total of 72 images),
      and six observers participated in this study. Observer responses were used to
      compute the fraction of correctly detected disks. A signal detection model was
      used to fit the recorded data from which CD characteristics were obtained.
      Repeated-measures analyses with mixed-effects linear models were performed for
      each of the six observers. All statistical tests were two sided and unadjusted
      for multiple comparisons. A P value of .05 or less was considered to indicate a
      significant difference. RESULTS: Statistical analysis revealed significantly
      better CD characteristics with 39- and 78-microm pixel sizes compared with 100
      microm pixel size for all disk diameters and phantom thicknesses (P<.001).
      Increase in phantom thickness degraded CD characteristics regardless of pixel
      size (P<.001). CONCLUSION: On the basis of the conditions of this study, reducing
      pixel size below 100 mum with low imaging system noise enhances the visual
      perception of small objects that correspond to typical microcalcifications.

PMID- 17522349
TI  - Satisfaction of radiologists in the United States: a comparison between 2003 and
      1995.
AB  - PURPOSE: To prospectively ascertain what characteristics of radiologists, their
      practices, and their work environment affect professional satisfaction and to
      describe recent changes in satisfaction. MATERIALS AND METHODS: Survey
      respondents were guaranteed confidentiality. Those who consented to participate
      were informed of the nature of the study. The authors analyzed nonindividually
      identified data from the American College of Radiology 2003 Survey of
      Radiologists, a nationally representative, confidential, stratified random-sample
      mail survey of radiologists in the United States, which had a 63% response rate,
      with a total of 1924 responses. Data were weighted to be representative of all
      U.S. radiologists and were analyzed by using univariate and multivariate
      analyses. The five answer options to questions regarding level of satisfaction
      corresponded to scores of +2, +1, 0, -1, and -2. Results were compared with those
      of a similar 1995 survey. RESULTS: Although 93% of radiologists enjoyed radiology
      very much or somewhat, the mean satisfaction score for posttraining
      professionally active radiologists decreased from 1.62 in 1995 to 1.47 in 2003.
      Thirty-two percent of radiologists reported enjoying radiology more than 5 years
      ago; 41% said they enjoyed it less. Excessive workload reduced current
      satisfaction and satisfaction relative to 5 years ago. Working in the Midwest
      enhanced current satisfaction and satisfaction relative to 5 years ago. Practice
      type and practice ownership had more varied effects on professional satisfaction;
      subspecialty type had relatively little effect. In 2003, medicolegal climate,
      workload, and reimbursement and/or financial pressures were the three most common
      reasons for decreased satisfaction. In 1995, interference from managed care;
      government regulations, control, and red tape; and increased administrative
      burden were the three most common reasons. Lifestyle and/or work hours, and
      income were the most common causes of increased satisfaction in 2003, but these
      were also often mentioned as causes of decreased satisfaction. CONCLUSION:
      Radiologists have higher levels of professional satisfaction than do other
      physicians; however, as with physicians overall, their satisfaction has decreased
      over time.

PMID- 17522350
TI  - Prior exercise improves age-dependent vascular endothelial growth factor
      downregulation and angiogenesis responses to hind-limb ischemia in old rats.
AB  - Downregulation of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial
      growth factor (VEGF) are shown to be involved in age-dependent impairment of
      angiogenesis. In this study, we explore whether prior exercise is able to affect
      these molecular patterns favorably and to enhance neoangiogenesis in old Wistar
      rats with hind-limb ischemia. At day 7 after surgery, HIF-1alpha and VEGF
      expression increased in the ischemic muscle of trained animals. Exercise
      increased capillary density and limb perfusion as revealed by histologic,
      angiographic, and dyed bead techniques. Furthermore, exercise capacity and limb
      trophism have significantly improved in trained aged rats. In these animals, the
      reduction of VEGF serum levels has reflected the comprehensive improvement in
      local ischemia evoked by exercise. In conclusion, prior exercise represents a
      valid tool to counteract age-related molecular alterations resulting in impaired
      angiogenesis in response to ischemia.

PMID- 17522351
TI  - Age-related increase of insoluble, phosphorylated small heat shock proteins in
      human skeletal muscle.
AB  - Among mammalian heat shock proteins (Hsps), small Hsps (sHsps) are constitutively
      expressed in skeletal muscles. We investigated age-related changes of
      phosphorylation and cellular distribution of representative sHsps (Hsp27 and
      alphaB-crystallin) in human vastus lateralis muscle under resting conditions. We
      also examined upstream kinases which may be responsible for phosphorylation of
      sHsps, namely p38 mitogen-activated protein kinase (MAPK), MAPK-activated protein
      kinase-2, and extracellular signal-regulated kinase-1/2. The study groups
      consisted of nine young (15-38 years old) and nine aged (51-79 years old)
      patients who underwent orthopedic surgery. sHsps protein levels were higher in
      the insoluble fraction of aged muscles. The phosphorylated states of sHsps were
      enhanced in both the soluble and insoluble fraction of aged patients. The
      phosphorylated form of each upstream kinase was elevated in aged patients.
      Ubiquitinated proteins accumulated in the insoluble fractions of aged muscles.
      Aging mechanisms may affect the activation process of MAPKs, and the
      phosphorylation and accumulation of sHsps.

PMID- 17522352
TI  - Age-associated decrease in proteasome content and activities in human dermal
      fibroblasts: restoration of normal level of proteasome subunits reduces aging
      markers in fibroblasts from elderly persons.
AB  - We measured proteasome activities and the levels of proteasome subunits in dermal
      fibroblasts from individuals aged 20-82 years. Proteasome activities changed with
      age in a biphasic manner, decreasing significantly up to 50 years of age and
      showing no significant change between 50 and 78 years of age. Similarly,
      proteasome activities in replicatively senescent dermal fibroblasts showed a
      passage-dependent biphasic change. We confirmed that the decreases in proteasome
      activities were accompanied by the accumulation of oxidized and ubiquitinated
      proteins. The decline in proteasome activities in aging fibroblasts was
      associated with a decrease in the expression of proteasome subunits. We found
      that the restoration of the normal level of proteasome catalytic subunits, using
      a lentivirus gene-delivery system, decreased the severity of the aging markers in
      dermal fibroblasts from elderly donors. These findings suggest that proteasome
      malfunction may contribute to the aging process in human skin and that the
      maintenance of normal proteasome activities could delay skin aging.

PMID- 17522353
TI  - Reduced age-related cataracts among elderly persons who reach age 90 with
      preserved cognition: a biomarker of successful aging?
AB  - Tissue damage due to oxidative stress has been implicated in aging, memory loss,
      and cataract formation. We hypothesized that persons who achieved exceptional
      longevity with preserved cognition (successful aging [SAG]) would exhibit a lower
      rate of age-related cataract (ARC) than the general population. The age-specific
      rates of ARC for a group of 100 (50 male, 50 female) elderly persons who reached
      at least age 90 years with preserved cognition were compared to the corresponding
      rates of ARC reported in five population-based studies. The principal finding of
      this report was that the SAG group manifested a significant reduction in the age
      specific rate and lifetime cumulative incidence of ARC compared to the general
      population. Steroid use, alcohol consumption, gout, and skin lesions resulting
      from excessive sun exposure emerged as risk factors. Our findings suggest that
      the progressive development of lens opacities may be reflective of degenerative
      events occurring more generally throughout the body.

PMID- 17522354
TI  - Association of interleukin-19 gene polymorphisms with age.
AB  - We previously demonstrated a significant association of the interleukin-10 (IL
      10) -819 T/C polymorphism with age. IL-19 stimulates the production of IL-10, and
      the IL-19 gene is located adjacent to the telomere side of the IL-10 gene. To
      explore the relationship between IL-19 single nucleotide polymorphisms (SNPs) and
      age, we genotyped 500 Japanese individuals (mean age: 56.7 years, range 19-100)
      for IL-19 Ser175Phe (T/C), -513 T/C, 1098 G/T (intron 1) and 5420 G/C (5'
      untranslated region). Three of four SNPs (Ser175Phe, -513 T/C and 1098 G/T)
      exhibited a weak but significant association with age by chi-square test and
      logistic regression analysis (p <.05). IL-19 Ser175Phe was in linkage
      disequilibrium with -513 T/C and 1098 G/T, but not with IL-10 -819 T/C. These
      data suggest that IL-19 polymorphisms may be associated with age in a Japanese
      population.

PMID- 17522355
TI  - A year of excellence in geriatric research and some new dishes on the menu.

PMID- 17522356
TI  - Use of antiplatelet drugs in secondary prevention in older persons with
      atherothrombotic disease.
AB  - Unless there are contraindications to the use of aspirin, aspirin should be used
      in treating patients with acute myocardial infarction (MI) and continued
      indefinitely to reduce vascular death, nonfatal MI, and nonfatal stroke.
      Clopidogrel added to aspirin has been shown to be beneficial in the treatment of
      patients with acute ST-elevation MI. Patients with unstable angina or non-ST
      elevation MI should be treated with aspirin plus clopidogrel for at least 9
      months to reduce 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. Extended release dipyridamole plus
      low dose aspirin has been shown to be more efficacious than low dose aspirin in
      only one large study, and is associated with an insignificant increase in
      nonfatal MI and vascular death over low dose aspirin alone. Clopidogrel is
      significantly more effective than aspirin in reducing vascular death, nonfatal
      MI, and nonfatal stroke in patients with peripheral arterial disease.

PMID- 17522357
TI  - Four-year lower extremity disability trajectories among African American men and
      women.
AB  - BACKGROUND: We examined 4-year lower extremity disability trajectories. METHODS:
      Nine hundred ninety-eight African American men and women 49-65 years old were
      evaluated at baseline and at four annual follow-ups. Lower extremity disability
      was the number of difficulties with nine standard activities of daily living
      (ADL), instrumental ADLs (IADL), and lower body function items. Mixed-effect
      models were used. RESULTS: The 9-item lower extremity disability measure had
      factorial validity and high reliability (alpha > 0.88). The mean baseline lower
      extremity disability score was 2.43, and at the subsequent follow-ups it was
      2.23, 2.35, 2.60, and 2.70. The mixed-effect model included significant random
      intercept and aging effects. Fixed factors with the largest effect sizes (all p <
      or =.001) were physical performance (-0.238 lower extremity disabilities per
      point on the Short Physical Performance Battery [SPPB]), fear of falling (1.094),
      poor or fair self-rated health (0.735), self-reported arthritis (0.659),
      clinically relevant levels of depression symptoms (0.641), body mass index (0.047
      per kg/m(2) unit), aging (0.082 per year), and asthma (0.558). CONCLUSIONS: To
      improve lower extremity disability trajectories among African Americans,
      interventions should focus on improving SPPB scores. In addition, fear of
      falling, poor or fair self-rated health, and clinically relevant levels of
      depression symptoms should be considered potential intervention candidates
      warranting further evaluation.

PMID- 17522358
TI  - Terminal trajectories of functional decline in the long-term care setting.
AB  - BACKGROUND: Little is known about the terminal trajectories of functional decline
      among long-term care (LTC) residents dying with different diseases. METHODS: A
      retrospective cohort study was performed on 747 individuals aged 65 or older who
      died between January 1994 and December 2004 in a 675-bed LTC facility in
      Massachusetts. Three study groups were created: advanced dementia, n = 314 (42%);
      terminal cancer, n = 63 (8%); and organ failure (congestive heart failure and
      chronic obstructive pulmonary disease), n = 370 (50%). Quarterly scores of 7
      activities of daily living (ADLs) during the last year of life derived from the
      Minimum Data Set were compared among the three groups. Each activity was rated
      from 0 to 4 (higher scores indicate more dependence; total range, 0-28). RESULTS:
      The mean age of all individuals at death was 91 +/- 6 (standard deviation) years.
      Functional decline was greatest during the last 3 months of life, but this
      decline was most precipitous in the terminal cancer and organ failure groups
      compared to the advanced dementia group. The mean change in ADL scores during the
      last year of life differed among the three groups (p <.001), with the greatest
      decline in the terminal cancer group (from initial score 13 to final score 25),
      followed by the organ failure group (13 to 22), and finally, the advanced
      dementia group (24 to 27). CONCLUSIONS: The terminal trajectories of functional
      decline among LTC residents vary by underlying diseases. An understanding of
      these trajectories may be useful to clinicians and families caring for LTC
      residents near the end of life.

PMID- 17522359
TI  - Choice stepping response and transfer times: effects of age, fall risk, and
      secondary tasks.
AB  - BACKGROUND: Deterioration with age of physiological components of balance control
      increases fall risk. Avoiding a fall can also require higher level cognitive
      processing to select correct motor and stepping responses. Here we investigate
      how a competing cognitive task and an obstacle to stepping affect the initiation
      and execution phases of choice stepping reaction times in young and older people.
      METHODS: Three groups were studied: young persons (YOUNG: 23-40 years, n = 20),
      older persons with a low risk of falls (OLR: 75-86 years, n = 18), and older
      persons with a high risk of falls (OHR: 78-88 years, n = 22). Four conditions
      were examined: choice stepping, choice stepping + obstacle, choice stepping +
      working memory task, and choice stepping + working memory task + obstacle. Step
      response and transfer times were measured for each condition, in addition to
      hesitant stepping, contacts with the obstacle and errors made in the memory test.
      RESULTS: Older participant groups had significantly longer response and transfer
      times than the young group had, and the OHR group had significantly longer
      response and transfer times than the OLR group had. There was a significant Group
      x Secondary task interaction for response time (F(2,215) = 12.6, p <.001). With
      the memory task, response time was minimally affected in the YOUNG (7% increase,
      p =.11) but was slowed significantly in the OLR fallers (42% increase, p <.001)
      and more so in the OHR fallers (48% increase, p <.001). The obstacle had a small
      but significant effect on response time (9.4%) and a larger effect on transfer
      time (43.3%), with no differences among the groups. Errors in stepping,
      performing the secondary task and contacting the obstacle increased with age and
      fall risk. CONCLUSIONS: Compared with young people, older people, and more so
      those at risk of falling, have an impaired ability to initiate and execute quick,
      accurate voluntary steps, particularly in situations where attention is divided.

PMID- 17522360
TI  - Reliability of maximal voluntary muscle strength and power testing in older men.
AB  - BACKGROUND: Maximal voluntary muscle strength (MVMS) and leg power are important
      measures of physical function in older adults. We hypothesized that performing
      these measures twice within 7-10 days would demonstrate a >5% increase due to
      learning and familiarization of the testing procedures. METHODS: Data were
      collected from three studies in older adult men (60-87 years) and were divided
      into two cohorts defined by study site and type of exercise equipment. MVMS was
      assessed in 116 participants using the one-repetition maximum method at two
      separate study visits for the chest press, latissimus pull-down, leg press, leg
      flexion, and leg extension exercises along with unilateral leg extension power.
      RESULTS: Test-retest scores were not different and did not exceed 0.8 +/- 9.0% in
      Cohort 1 or 2.3 +/- 9.8% in Cohort 2, except for leg extension, which improved by
      6.6 +/- 14.4% (p <.009) and 3.4 +/- 6.8% (p <.016), respectively. Repeat tests
      were closely correlated with initial tests (all p <.001). Pearson correlation
      coefficients ranged from 0.74 for leg extension power to 0.96 for leg press.
      Coefficients of variation were <10% (4.2%-9.0%) for all exercises except for leg
      extension power, which was 15.5%. CONCLUSIONS: Our findings demonstrated that
      test-retest measures of MVMS and power in older adult men do not differ by more
      than 2.3% except for leg extension, and have relatively low coefficients of
      variation using data collected from three studies. Moreover, these findings were
      similar between two study sites using different equipment, which further supports
      the reliability of MVMS and power testing in older adult men.

PMID- 17522361
TI  - The relationship between medical comorbidity and self-rated pain, mood
      disturbance, and function in older people with chronic pain.
AB  - BACKGROUND: Aging is associated with greater risk for many illnesses and the
      prospect of multiple, concurrent disease states. Chronic pain is also very common
      in advanced age, and there is likely to be a relationship with comorbid burden,
      but few studies have examined this issue. This study tests the hypothesis that
      comorbid burden is associated with greater levels of self-reported pain and
      associated disturbance in mood and function. METHODS: Psychometric and medical
      data were collected from 562 patients (mean age = 76.3 years) attending a
      geriatric pain clinic. The number of categories endorsed on the Cumulative
      Illness Rating Scale (CIRS) score was used to measure accumulated comorbid
      burden. These groups were tested for differences in the severity of self-reported
      pain. The predictive capacity of comorbid burden for explaining variance in mood
      disturbance and functional disability was assessed after controlling for any
      differences in age and severity of pain. RESULTS: Over 50% of the sample had
      three or more comorbid problems. Groups with greater levels of comorbidity scored
      higher on the Present Pain Intensity Index, the sensory and affective subscales
      of the McGill Pain Questionnaire. Multiple regression analysis showed that the
      CIRS score explained a significant proportion of the variance in scores on the
      Geriatric Depression Scale (4.1%), Human Activities Profile (4.8%), and the
      physical domain of the Sickness Impact Profile (5.9%). CONCLUSION: Greater levels
      of comorbidity are associated with reports of more severe pain, more depressive
      symptoms, reduced activity levels, and higher physical impact from pain.

PMID- 17522362
TI  - Dietary phytoestrogen intake and cognitive function in older women.
AB  - BACKGROUND: Aging is associated with a decline in cognitive function; we explored
      the possible influence of dietary phytoestrogens on this decline. METHODS: We
      conducted a cross-sectional study in 301 Dutch women aged 60-75 years. Dietary
      isoflavone and lignan intake was assessed with a food-frequency questionnaire
      covering habitual diet in the year preceding enrolment. The endpoints were
      cognitive function measured in three domains: memory, processing capacity and
      speed, and executive function. Data were analyzed using linear regression models,
      after adjusting for confounders. RESULTS: No association between dietary
      isoflavone intake and cognitive function was found. High lignan intake was
      associated with a better performance in processing capacity and speed, and in
      executive function (p for trend over quartiles =.01 and.02, respectively).
      CONCLUSIONS: This finding calls for further research to elucidate the relatively
      underexplored role of lignans within the range of phytoestrogens.

PMID- 17522363
TI  - Psychosocial risk factors and the metabolic syndrome in elderly persons: findings
      from the Health, Aging and Body Composition study.
AB  - BACKGROUND: Psychosocial factors have been associated with metabolic
      abnormalities that increase the risk of cardiovascular disease and diabetes. This
      study investigated the cross-sectional relationship between psychosocial risk
      factors and the metabolic syndrome in a community-based sample of older persons.
      METHODS: Participants were 2917 persons aged 70-79 years enrolled in the Health,
      Aging and Body Composition study. Depressive and anxiety symptoms, negative life
      events, and inadequate emotional support were assessed, and a summary
      psychosocial risk index was calculated. Metabolic syndrome was defined as three
      or more of the following criteria: abdominal obesity, high triglycerides, low
      high-density lipoprotein (HDL) cholesterol, high fasting glucose, and high blood
      pressure. RESULTS: Negative life events and inadequate emotional support
      increased the odds of having metabolic syndrome after adjustment for demographic
      and lifestyle variables (odds ratio [OR] per life event = 1.13, 95% confidence
      interval [CI] = 1.05-1.22; OR = 1.35, 95% CI = 1.10-1.66, respectively). The
      relationship between depressive symptoms and metabolic syndrome was only found in
      white (OR per standard deviation [SD] = 1.11, 95% CI = 1.01-1.23), but not in
      black (OR per SD = 0.97, 95% CI = 0.86-1.11) persons. Anxiety symptoms were
      significantly associated with metabolic syndrome in men (OR per SD = 1.13, 95% CI
      = 1.00-1.28), but not in women (OR per SD = 0.98, 95% CI = 0.89-1.08). Moreover,
      a higher score on the psychosocial risk index was associated with an increased
      probability of having the metabolic syndrome (OR = 1.30, 95% CI = 1.12-1.52).
      CONCLUSIONS: In the elderly population, different psychosocial risk factors are
      associated with a higher prevalence of the metabolic syndrome. Whether reduction
      or better management of psychosocial risk factors can improve the metabolic
      profile remains to be demonstrated.

PMID- 17522364
TI  - Cholinesterase inhibitors and Alzheimer's disease outcomes.

PMID- 17522365
TI  - A novel mutation of gene CBFA1/RUNX2 in cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia
      characterised by abnormal clavicles, patent sutures and fontanelles,
      supernumerary teeth, short stature, and a variety of other skeletal changes. The
      disease gene is CBFA1/RUNX2, which is mapped to chromosome 6p21. Inactivation of
      the CBFA1/RUNX2 gene by mutations is involved in the skeletal defects that occur
      in patients with CCD. CBFA1/RUNX2 controls the differentiation of precursor cells
      into osteoblasts and is essential for membranous as well as endochondral bone
      formation. In this study of a 14-yr-old boy with typical CCD phenotype, the
      authors found a novel CBFA1/RUNX2 gene mutation. All of the amplified segments
      from the patient's CBFA1/RUNX2 gene were identical to those obtained in controls,
      except for the one spanning the exon 7 and intron/exon boundary regions. Direct
      sequencing of the PCR product showed a heterozygous T-to-A transition mutation at
      nucleotide 1182 in exon 7, leading to Y394X mutation. The predicted protein
      product lacks 128 amino acids, including part of the PST domain. Identification
      of this novel mutation constitutes a further step in elucidating the pathogenesis
      of this autosomal disorder.

PMID- 17522366
TI  - C4d positivity is often associated with acute cellular rejection in renal
      transplant biopsies following Campath-1H (Alemtuzumab) induction.
AB  - Peritubular capillary C4d positivity, a marker for antibody-mediated rejection,
      is observed in approximately 20-50% of indicated renal transplant biopsies and in
      just 2% of unremarkable protocol biopsies. However, C4d staining has not been
      evaluated in protocol renal biopsies from patients with Campath-1H induction
      treatment, and the association between various types of inflammatory cells and
      acute antibody-mediated rejection is unclear. This study investigated the rates
      of C4d positivity in unremarkable protocol renal biopsies, biopsies with acute
      tubular necrosis (ATN), and biopsies with acute cellular rejection (ACR), all
      following Campath-1H treatment and post-operative immunosuppression. There was
      low positivity of C4d staining in both the protocol and ATN groups, but the ACR
      group had a 47.2% rate of positivity (combining focal and diffuse positive
      cases). Since Campath-1H treatment caused significant depletion of circulating
      lymphocytes but not circulating monocytes in renal recipients, this study also
      investigated the role of monocytes in humoral rejection. In ACR cases, CD68
      positive monocytes were composed of 59.4 +/- 4.69% inflammatory cells, which was
      significantly higher than CD3 positive lymphocytes (38.9 +/- 4.4%). Co
      localization of positive C4d staining in endothelium and marginating CD68
      positive monocytes was illustrated by double staining. Our data indicate that
      acute antibody-mediated rejection occurs much more frequently in renal
      transplants with ACR. Moreover, the high percentage of monocytes observed in ACR
      cases (due to monocytes being less sensitive to Campath-1H depletion) suggests
      that monocytes are involved in antibody-mediated rejection.

PMID- 17522367
TI  - Expression of cytokeratin markers, ER-alpha, PR, HER-2/neu, and EGFR in pure
      ductal carcinoma in situ (DCIS) and DCIS with co-existing invasive ductal
      carcinoma (IDC) of the breast.
AB  - Previously, we showed that pure ductal carcinoma in situ (DCIS) of the breast can
      be divided into 3 subtypes (luminal, basal/stem, and null) based on the
      expression of 5 cytokeratin (CK) markers: CK5/6, CK14, CK17 (stem/basal), and
      CK8, CK18 (luminal). The distributions of CK subtypes were associated with
      nuclear grade and differential expression of estrogen receptor-alpha (ER-alpha),
      progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor
      (EGFR). In this study, we further explore the expression patterns of CK markers,
      ER-alpha, PR, HER-2/neu, and EGFR by immunohistochemical (IHC) analysis of 99
      cases of pure DCIS and 96 cases of DCIS with co-existing invasive ductal
      carcinoma (DCIS/IDC). We show that between high-grade DCIS and DCIS/IDC, there
      are differential expression patterns for ER-alpha, PR, and EGFR in corresponding
      CK subtypes, suggesting that at least some pure DCIS is molecularly distinct from
      DCIS/IDC. In most cases there is a high degree of co-expression of these markers
      between DCIS and the co-existing IDC, suggesting that DCIS is frequently a
      precursor lesion for co-existing IDC. The rate of discordant expression of these
      markers is low and is more frequently associated with high-grade carcinoma,
      suggesting that other molecular pathways also may also be present. There are
      significant differences in the expression of these molecular markers between high
      grade and non-high-grade carcinomas, supporting the view that high-grade and non
      high-grade carcinomas of the breast are molecularly distinct entities.

PMID- 17522368
TI  - Role of a molecular variant of rat atrial natriuretic Peptide gene in vascular
      remodeling.
AB  - Previous studies in a hypertensive animal model of stroke and in humans showed
      that mutations of the atrial natriuretic peptide (ANP) gene are associated with
      increased risk of stroke. To elucidate the vascular disease mechanisms that
      result from structural modifications of the ANP gene, we investigated a coding
      mutation of the ANP gene in stroke-prone spontaneously hypertensive rats (SHRsp).
      This mutation leads to a Gly/Ser transposition in the prosegment of ANP. We found
      that presence of this mutation is associated with increased immunostaining of ANP
      in the wall of SHRsp cerebral vessels. The mutation causes a major inhibitory
      effect on endothelial cell proliferation, as assessed by thymidine incorporation,
      and on angiogenesis, as determined by an endothelial cell tube formation assay,
      in human umbilical vein endothelial cells (HUVEC) exposed to ANP/SHRsp. These in
      vitro findings show that the SHRsp-derived form of ANP has an inhibitory effect
      on vascular remodeling and they provide further support for a role of the ANP
      gene in the pathogenesis of cerebrovascular disease in the animal model.

PMID- 17522369
TI  - Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB
      pathways in high risk neuro-blastoma, with cell cycle and protein analyte
      correlates.
AB  - Morphoproteomic analysis reveals the constitutive activation of the mTOR, ERK,
      and NF-kappaB pathways in high risk neuroblastoma (HRN) cases as evidenced by (a)
      collective commonalities of: phosphorylated (p)-mTOR, p70S6K, ERK 1/2, and NF
      kappaBp65 protein analytes using phosphospecific probes directed against sites of
      activation; (b) nuclear translocation of p-p70S6K, p-ERK 1/2, and p-NF-kappaBp65;
      and (c) correlative expression of the S phase-associated kinase Skp-2 (at a
      relatively high percentage in tumoral nuclei) and of the anti-apoptotic protein
      bcl-2. Based on a review of the literature, these preliminary observations appear
      to be the first morphoproteomic study on primary neuroblastomas.

PMID- 17522370
TI  - CD52 antigen may be a therapeutic target for eosinophilic rhinosinusitis.
AB  - Allergic rhinosinusitis involves several types of inflammatory cells. The
      dominant inflammatory cells include mast cells, eosinophils, lymphocytes, and
      monocytes/macrophages. Since eosinophils are one type of inflammatory cell that
      is often related to allergy, we investigated in this study whether the
      eosinophils present in rhinosinusitis may be potential targets for CD52 antibody
      treatment. First, we found that circulating eosinophils in renal recipients were
      almost completely depleted after iv bolus of treatment with Campath-1H, a
      humanized antibody against CD52 antigen. Second, we showed morphologically that
      eosinophils, lymphocytes, and monocytes gave positive staining reactions for
      CD52. Third, using an automated clinical imaging system, we found that tissue
      sections of sinus contents with prominent eosinophils (eosinophilic
      rhinosinusitis) yielded significantly higher CD52 staining scores than those with
      lymphocytes as the dominant component (lymphocytic rhinosinusitis). These
      findings indirectly support the hypothesis that CD52 may be a target for treating
      eosinophilic rhinosinusitis with Campath 1H.

PMID- 17522371
TI  - Simple immunohistochemical staining method using large sized gold colloid
      conjugated secondary antibody.
AB  - To test the feasibility of semiquantitative immunohistochemical staining (IHC)
      with large sized gold conjugated secondary antibody (gold-2 degrees Ab), we used
      beads covered with a known amount of primary antibody and a secondary antibody
      conjugated with gold colloid particles (20 and 40 nm in diameter), and we
      compared the results to those obtained by enzyme IHC. Beads coated with 6 graded
      amounts of mouse IgG molecules showed 6 levels of color intensity. The graded
      color intensities could readily be distinguished. The color developed as soon as
      we added gold-2 degrees Ab, and the intensities were stable for 1 wk. Enzyme IHC
      using identical beads showed dregs of pigment after incubation in DAB for 5 min.
      The large sized gold-2 degrees Ab showed strong signals on cell surfaces;
      application of the large sized gold-2 degrees Ab to paraffin-embedded tissue
      sections was also feasible. The color was bright red and was easier to
      differentiate from hemosiderin pigment than the color developed by enzyme IHC. In
      conclusion, gold IHC with large sized gold-2 degrees Ab is superior to enzyme IHC
      for quantification of antigens via IHC. Gold IHC is especially recommended for
      tissues with many macrophages, such as bone marrow and spleen.

PMID- 17522372
TI  - Decrease in inflammatory cardiovascular risk markers in hyperlipidemic diabetic
      patients treated with fenofibrate.
AB  - The goal was to investigate the effect of micronized fenofibrate, a hypolipidemic
      drug, on inflammatory markers and proinsulin in patients with type 2 diabetes who
      had hyperlipidemia. Thirty-nine patients were treated with micronized fenofibrate
      (200 mg/day for 12 wk). Erythrocyte sedimentation rate (ESR), fibrinogen, high
      sensitivity C-reactive protein (hs CRP), and proinsulin levels were measured at
      baseline and after 12 wk of therapy. Micronized fenofibrate significantly reduced
      serum triglyceride, cholesterol, and uric acid levels (all p <0.0001) and
      increased high-density lipoprotein (HDL)-cholesterol (p <0.001) and creatinine
      levels (p <0.0001). Micronized fenofibrate also significantly decreased
      fibrinogen (421 +/- 152 vs 344 +/- 81 mg/dl, p <0.001), hs-CRP (3.3 +/- 3.3 vs
      2.1 +/- 1.8 mg/L, p <0.01), and ESR (19.1 +/- 24.8 vs 9.7 +/- 8.7 mm/hr, p
      <0.01), but did not change proinsulin levels. The correlations among changes of
      hs-CRP, fibrinogen, and ESR were high. Although correlation among the decreases
      in inflammatory markers (ESR, fibrinogen, and hs-CRP) was significant, there was
      no significant correlation between the changes of lipid profile and inflammatory
      markers. In conclusion, after 12 wk, micronized fenofibrate therapy significantly
      decreased 3 inflammatory markers (hs-CRP, ESR, and fibrinogen) and improved the
      lipid profile by decreasing serum triglyceride, cholesterol, and non-HDL
      cholesterol levels and increasing HDL-cholesterol; however, it did not change
      serum proinsulin level, a pancreatic stress marker.

PMID- 17522373
TI  - Eluate testing following microscopically positive direct antiglobulin tests with
      anti-IgG.
AB  - The direct antiglobulin test (DAT) demonstrates the presence of immunoglobulin
      (eg, IgG) or complement on the surface of red blood cells (RBCs). Immunoglobulin
      can be removed from RBCs by elution. The liquid end-product of elution
      procedures, the eluate, can be evaluated by antibody identification procedures.
      Antibody identification studies following acid/EDTA elution and DATs performed in
      our immunohematology laboratory during 2005 were evaluated to determine the
      usefulness of eluate testing following a microscopically positive IgG DAT. In
      total, 310 eluates were prepared during the year 2005; 146 of these eluates were
      derived from RBC samples with a microscopically positive DAT. The remaining
      eluates were derived from RBC samples with macroscopically positive IgG DATs (85
      were weakly +; 32 were 1+; 40 were 2+; and 7 were 3+). Data were collected for
      the number and types of new antibodies (warm autoantibodies or alloantibodies)
      that were identified as a consequence of eluate testing. The incidence of new
      alloantibodies in the microscopically positive group (0.7%) was significantly
      lower than the combined incidence in the macroscopically positive groups (5.5%, p
      = 0.02). Based on these results, the authors conclude that performing antibody
      identification procedures on acid/EDTA eluates derived from RBC samples with
      microscopically positive IgG DATs has limited utility.

PMID- 17522374
TI  - Nitric oxide and prostaglandin response to group B streptococcal infection in the
      lung.
AB  - Group B streptococcus (GBS) causes a complex inflammatory process that involves
      prostaglandins (PG) and nitric oxide (NO). The goal of this study was to examine
      the inflammatory response to GBS in the lung and the co-regulation of the PG and
      NO pathways, if any, both in vitro and in vivo. Sprague Dawley rats were treated
      with various combinations of GBS, aminoguanidine (AG), a selective inducible
      nitric oxide synthase (iNOS) inhibitor, and L-arginine (LA), a NO donor. The mRNA
      expression of the COX 2 gene was studied by reverse transcriptase polymerase
      chain reaction (RTPCR) in rat lung tissue. The studies were confirmed in vitro
      using human lung epithelial (A549) cells treated with GBS, AG, and LA (in
      combinations similar to the rats) for 3 and 24 hr, after which PG E2 levels in
      the media were measured by enzyme linked immunosorbent assay (ELISA). COX 2 mRNA
      in rat lung tissue was significantly induced by GBS (p = 0.04), an effect that
      was suppressed by AG (p = 0.02). In the A549 cell line, PG E2 levels increased
      with GBS treatment at 3 and 24 hr (p <0.001). When AG was added, PG E2 levels
      were suppressed (p = 0.03) after 24 hr; LA partly reversed the suppression of PG
      E2 levels (p = 0.039). These data indicate that GBS infection causes significant
      COX 2 induction and PG E2 synthesis in lung tissue, regulated at least partly by
      the NO pathway. The interaction between the 2 pathways may play a pathogenic role
      in GBS lung infections and could be a potential target for pharmacological
      manipulation.

PMID- 17522375
TI  - Novel presentation of central core disease with nemaline bodies (rods) in the
      setting of diploid/triploid mosaicism.
AB  - Diploid/triploid mosaicism is an uncommon malformation syndrome thought to result
      from incorporation of the second polar body into a blastomere nucleus of the
      developing embryo. Clinical manifestations include mental and growth retardation,
      truncal obesity, body asymmetry, hypotonia, syndactyly, clino-/camptodactyly,
      malformed low-set ears, and small phallus. Although muscular atrophy has been
      documented in 35% of cases of diploid/triploid mosaicism, to our knowledge
      histologic evidence of myopathy has not been reported. We present a novel case of
      diploid/triploid mosaicism with evidence of central core disease and nemaline
      bodies (rods). The histologic and ultrastructural features are described. A
      review of the literature is provided, including discussion of the various
      theories regarding the co-expression of central cores and nemaline rods.

PMID- 17522376
TI  - Eosinophilic cholecystitis, with a review of the literature.
AB  - Eosinophilic cholecystitis (EC) is a rare entity that presents in a manner
      comparable to acute cholecystitis. The diagnosis is based on classical symptoms
      of cholecystitis with the presence of >90% eosinophilic infiltration within the
      gallbladder. We report the case of a 29-yr-old man who presented with unremitting
      right upper quadrant pain, chills, and loss of appetite. After confirmation of
      the diagnosis with ultrasound and hepatobiliary scan (HIDA), a cholecystectomy
      was performed. Pathologic examination of the excised gallbladder demonstrated
      submucosal infiltration with eosinophils, consistent with EC. Peripheral
      eosinophilia was not observed; the subject's blood eosinophil count did not
      exceed 3% during the period of observation. The patient was discharged with no
      further symptoms. Cases of EC have been infrequently reported since its original
      description in 1949. EC has been reported alone or in combination with
      manifestations such as eosinophilic cholangitis, hypereosinophilic syndromes
      (HES), and parasitic infestations. The patient described herein gave no
      indications of such previously suggested causes of EC. This report illustrates an
      authentic case of idiopathic EC.

PMID- 17522377
TI  - An unusual cause of elevated serum total beta hCG.
AB  - Human chorionic gonadotropin (hCG), a heterodimeric hormone consisting of an
      alpha (alpha) and a beta (beta) subunit, is used as a marker for the diagnosis of
      pregnancy, congenital defects, and choriocarcinoma. After excluding the common
      causes of elevated serum hCG, laboratory identification of false-positive or true
      results assists in guiding clinical management. Options include testing urine for
      hCG, serum for heterophile antibodies, and serum hCG by different immunoassays.
      We report the case of a non-pregnant patient with chronic renal failure who had a
      positive urine hCG test, an elevated serum hCG level by two different assays but
      normal by a third assay, and persistently elevated serum hCG levels after ruling
      out the likelihood of heterophile antibodies. The discrepancies were explained by
      the patient's impaired renal clearance and the molecular forms of hCG that were
      measured by each assay. This case illustrates the importance of the laboratory's
      role in understanding the causes of elevated serum hCG.

PMID- 17522378
TI  - Inventors of new laboratory and pathology terms.

PMID- 17522379
TI  - Ser170 controls the conformational multiplicity of the loop 166-175 in prion
      proteins: implication for conversion and species barrier.
AB  - The self-perpetuating conversion of cellular prion proteins (PrP(C)) into an
      aggregated beta-sheet rich conformation is associated with transmissible
      spongiform encephalopathies (TSE). The loop 166-175 (L1) in PrP(C), which
      displays sequence and structural variation among species, has been suggested to
      play a role in species barrier, in particular against transmission of TSE from
      cervids to domestic and laboratory animals. L1 is ordered in elk PrP, as well as
      in a mouse/elk hybrid (in which L1 of mouse is replaced by elk) but not in other
      species such as mice, humans, and bovine. To investigate the source and
      significance of L1 dynamics, we carried out explicit solvent molecular dynamics
      simulations (approximately 0.5 micros in total) of the mouse prion protein, the
      mouse/elk hybrid, and control simulations, in which the mouse sequence is
      reintroduced into the structure of the mouse/elk hybrid. We found that the
      flexibility of L1 correlates with the backbone dynamics of Ser170. Furthermore,
      L1 mobility promotes a substantial displacement of Tyr169, rupture of the Asp178
      Tyr128 and Asp178-Tyr169 side chain hydrogen bonds, as well as disruption of
      Tyr169-Phe175 pi-stacking interaction. The simulation results go beyond the
      available experimental data because they highlight the dependence of this network
      of interactions on residue 170 and L1 plasticity.

PMID- 17522380
TI  - Cathepsin cysteine proteases in cardiovascular disease.
AB  - Extracellular matrix (ECM) remodeling is one of the underlying mechanisms in
      cardiovascular diseases. Cathepsin cysteine proteases have a central role in ECM
      remodeling and have been implicated in the development and progression of
      cardiovascular diseases. Cathepsins also show differential expression in various
      stages of atherosclerosis, and in vivo knockout studies revealed that deficiency
      of cathepsin K or S reduces atherosclerosis. Furthermore, cathepsins are involved
      in lipid metabolism. Cathepsins have the capability to degrade low-density
      lipoprotein and reduce cholesterol efflux from macrophages, aggravating foam cell
      formation. Although expression studies also demonstrated differential expression
      of cathepsins in cardiovascular diseases like aneurysm formation, neointima
      formation, and neovascularization, in vivo studies to define the exact role of
      cathepsins in these processes are lacking. Evaluation of the feasibility of
      cathepsins as a diagnostic tool revealed that serum levels of cathepsins L and S
      seem to be promising as biomarkers in the diagnosis of atherosclerosis, whereas
      cathepsin B shows potential as an imaging tool. Furthermore, cathepsin K and S
      inhibitors showed effectiveness in (pre) clinical evaluation for the treatment of
      osteoporosis and osteoarthritis, suggesting that cathepsin inhibitors may also
      have therapeutic effects for the treatment of atherosclerosis.

PMID- 17522381
TI  - Characterization of two novel LPS-binding sites in leukocyte integrin betaA
      domain.
AB  - Lipopolysaccharide (LPS), a bacterial endotoxin, triggers deleterious systemic
      inflammatory responses when released into blood circulation, causing organ
      dysfunction and death. In response to LPS stimulation, CD14 and toll-like
      receptor (TLR)-4 elicit inflammatory signaling cascades. Although leukocyte
      integrins (CD11b/CD18 and CD11c/CD18) were reported to bind LPS and induce NF
      kappaB translocation, the evidence on such epitope location remains elusive. The
      present study aims to delineate the LPS-binding sites on the integrin CD18
      antigen and to design peptide(s) as potential prophylactic and/or therapeutic
      agents to modulate LPS effects in activated Jurkat cells. Epitope mapping
      analysis using a series of CD18 truncated variants revealed two putative LPS
      binding sites within the betaA region (216-248 and 266-318 a.a.), which were
      further confirmed by point mutation studies. Inhibition assay demonstrated that
      the CD18-betaA(266-318) peptide could block LPS binding in a dose-dependent
      manner. Our data also indicated that treatment with the CD18-peptide modulated
      TNF-alpha mRNA transcription via the NF-kappaB signaling pathway in LPS-activated
      Jurkat cells. In conclusion, we have identified two novel LPS-binding sites
      located at the CD18 betaA domain of leukocyte integrin, and the integrin peptide
      betaA(266-318) is shown to inhibit LPS binding and subsequent inflammatory
      events, having therapeutic implications to cure gram-negative endotoxemia.

PMID- 17522382
TI  - The SDF-1/CXCR4 ligand/receptor pair is an important contributor to several types
      of ocular neovascularization.
AB  - Hypoxia causes increased expression of several proteins that have the potential
      to promote neovascularization. Vascular endothelial growth factor (VEGF) is up
      regulated by hypoxia in the retina and plays a central role in the development of
      several types of ocular neovascularization, but the effects of other hypoxia
      regulated proteins are less clear. Stromal-derived factor-1 (SDF-1) and its
      receptor, CXCR4, have hypoxia response elements in the promoter regions of their
      genes and are increased in hypoxic liver and heart. In this study, we found that
      SDF-1 and CXCR4 are increased in hypoxic retina, with SDF-1 localized in glial
      cells primarily near the surface of the retina and CXCR4 localized in bone marrow
      derived cells. Glial cells also expressed CXCR4, which suggested the possibility
      of autocrine stimulation, but influx of bone marrow-derived cells is the major
      source of increased levels of CXCR4. High levels of VEGF in the retina in the
      absence of hypoxia also increased levels of Cxcr4 and Sdf1 mRNA. CXCR4
      antagonists reduced influx of bone marrow-derived cells into ischemic retina and
      strongly suppressed retinal neovascularization, VEGF-induced subretinal
      neovascularization, and choroidal neovascularization. These data suggest that SDF
      1 and CXCR4 contribute to the involvement of bone marrow-derived cells and
      collaborate with VEGF in the development of several types of ocular
      neovascularization. They provide new targets for therapeutic intervention that
      may help to bolster and supplement effects obtained with VEGF antagonists.

PMID- 17522383
TI  - Interaction of the endocytic scaffold protein Pan1 with the type I myosins
      contributes to the late stages of endocytosis.
AB  - The yeast endocytic scaffold Pan1 contains an uncharacterized proline-rich domain
      (PRD) at its carboxy (C)-terminus. We report that the pan1-20 temperature
      sensitive allele has a disrupted PRD due to a frame-shift mutation in the open
      reading frame of the domain. To reveal redundantly masked functions of the PRD,
      synthetic genetic array screens with a pan1DeltaPRD strain found genetic
      interactions with alleles of ACT1, LAS17 and a deletion of SLA1. Through a yeast
      two-hybrid screen, the Src homology 3 domains of the type I myosins, Myo3 and
      Myo5, were identified as binding partners for the C-terminus of Pan1. In vitro
      and in vivo assays validated this interaction. The relative timing of recruitment
      of Pan1-green fluorescent protein (GFP) and Myo3/5-red fluorescent protein (RFP)
      at nascent endocytic sites was revealed by two-color real-time fluorescence
      microscopy; the type I myosins join Pan1 at cortical patches at a late stage of
      internalization, preceding the inward movement of Pan1 and its disassembly. In
      cells lacking the Pan1 PRD, we observed an increased lifetime of Myo5-GFP at the
      cortex. Finally, Pan1 PRD enhanced the actin polymerization activity of Myo5-Vrp1
      complexes in vitro. We propose that Pan1 and the type I myosins interactions
      promote an actin activity important at a late stage in endocytic internalization.

PMID- 17522384
TI  - Interaction of SNAREs with ArfGAPs precedes recruitment of Sec18p/NSF.
AB  - Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
      proteins are key components of the fusion machinery in vesicular transport and in
      homotypic membrane fusion. We previously found that ADP-ribosylation factor
      GTPase activating proteins (ArfGAPs) promoted a conformational change on SNAREs
      that allowed recruitment of the small GTPase Arf1p in stoichiometric amounts.
      Here, we show that the ArfGAP Gcs1p accelerates vesicle (v)-target membrane (t)
      SNARE complex formation in vitro, indicating that ArfGAPs may act as folding
      chaperones. These SNARE complexes were resolved in the presence of ATP by the
      yeast homologues of alpha-soluble N-ethylmaleimide-sensitive factor attachment
      protein and N-ethylmaleimide-sensitive factor, Sec17p and Sec18p, respectively.
      In addition, Sec18p and Sec17p also recognized the "activated" SNAREs even when
      they were not engaged in v-t-SNARE complexes. Here again, the induction of a
      conformational change by ArfGAPs was essential. Surprisingly, recruitment of
      Sec18p to SNAREs did not require Sec17p or ATP hydrolysis. Moreover, Sec18p
      displaced prebound Arf1p from SNAREs, indicating that Sec18p may have more than
      one function: first, to ensure that all vesicle coat proteins are removed from
      the SNAREs before the engagement in a trans-SNARE complex; and second, to resolve
      cis-SNARE complexes after fusion has occurred.

PMID- 17522385
TI  - Replication fork velocities at adjacent replication origins are coordinately
      modified during DNA replication in human cells.
AB  - The spatial organization of replicons into clusters is believed to be of critical
      importance for genome duplication in higher eukaryotes, but its functional
      organization still remains to be fully clarified. The coordinated activation of
      origins is insufficient on its own to account for a timely completion of genome
      duplication when interorigin distances vary significantly and fork velocities are
      constant. Mechanisms coordinating origin distribution with fork progression are
      still poorly elucidated, because of technical difficulties of visualizing the
      process. Taking advantage of a single molecule approach, we delineated and
      compared the DNA replication kinetics at the genome level in human normal primary
      and malignant cells. Our results show that replication forks moving from one
      origin, as well as from neighboring origins, tend to exhibit the same velocity,
      although the plasticity of the replication program allows for their adaptation to
      variable interorigin distances. We also found that forks that emanated from
      closely spaced origins tended to move slower than those associated with long
      replicons. Taken together, our results indicate a functional role for origin
      clustering in the dynamic regulation of genome duplication.

PMID- 17522386
TI  - Clinicopathologic correlation in PGRN mutations.
AB  - BACKGROUND: Frontotemporal dementia (FTD) has been linked to the microtubule
      associated protein tau (MAPT) gene region of chromosome 17. However, many
      chromosome-17 linked FTLDs do not have MAPT mutations or tau protein deposits,
      but have ubiquitin positive, tau and alpha-synuclein negative inclusions.
      Mutations in the progranulin (PGRN) gene, located 1.7 Mb from MAPT at 17q21.31,
      were recently discovered in some of these individuals. The pathologic phenotype
      in all cases has thus far included ubiquitinated neuronal intranuclear inclusions
      (NIIs) and neuronal cytoplasmic inclusions (NCIs). METHODS: PGRN mutation
      analysis was performed in 12 individuals. Informed consent was obtained from next
      of kin under an IRB-approved protocol. We compared clinical and pathologic
      findings in those cases with and without PGRN mutations. RESULTS: PGRN mutations
      were found in four patients, two with clinical FTD and a positive family history,
      and two with clinical primary progressive aphasia (PPA), one with and one without
      a family history. All four cases with, and five of eight cases without, PGRN
      mutations had ubiquitinated NCIs and NIIs. Brains of individuals with PGRN
      mutations are associated with more frequent frontal NCIs and dystrophic neurites,
      less frequent dentate gyrus NCIs, and more frequent striatal NIIs than FTLD-U
      cases without PGRN mutations. CONCLUSION: PGRN mutations at 17q21 may occur in
      apparently sporadic frontotemporal lobar dementia with ubiquitinated inclusions
      cases and in cases presenting with either primary progressive aphasia or the
      behavioral variant of frontotemporal dementia. Some cases without PGRN mutations
      also have ubiquitinated neuronal intranuclear inclusions. Clinicopathologic
      differences are observed among individuals with and without PGRN mutations.

PMID- 17522387
TI  - Practice parameter: treatment of nervous system Lyme disease (an evidence-based
      review): report of the Quality Standards Subcommittee of the American Academy of
      Neurology.
AB  - OBJECTIVE: To provide evidence-based recommendations on the treatment of nervous
      system Lyme disease and post-Lyme syndrome. Three questions were addressed: 1)
      Which antimicrobial agents are effective? 2) Are different regimens preferred for
      different manifestations of nervous system Lyme disease? 3) What duration of
      therapy is needed? METHODS: The authors analyzed published studies (1983-2003)
      using a structured review process to classify the evidence related to the
      questions posed. RESULTS: The panel reviewed 353 abstracts which yielded 112
      potentially relevant articles that were reviewed, from which 37 articles were
      identified that were included in the analysis. CONCLUSIONS: There are sufficient
      data to conclude that, in both adults and children, this nervous system infection
      responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B
      recommendation). Although most studies have used parenteral regimens for
      neuroborreliosis, several European studies support use of oral doxycycline in
      adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving
      parenteral regimens for patients with parenchymal CNS involvement, other severe
      neurologic symptomatology, or failure to respond to oral regimens. The number of
      children (> or =8 years of age) enrolled in rigorous studies of oral vs
      parenteral regimens has been smaller, making conclusions less statistically
      compelling. However, all available data indicate results are comparable to those
      observed in adults. In contrast, there is no compelling evidence that prolonged
      treatment with antibiotics has any beneficial effect in post-Lyme syndrome (Level
      A).

PMID- 17522388
TI  - Serum high-density lipoprotein cholesterol and risk of non-hodgkin lymphoma.
AB  - Lymphoma patients often exhibit abnormal lipid metabolism. Recent evidence,
      however, suggests that a decrease in circulating high-density lipoprotein
      cholesterol (HDL-C) may occur during lymphomagenesis, reflecting underlying
      etiology such as inflammation. We investigated the relationship between
      prediagnostic HDL-C and non-Hodgkin lymphoma (NHL) in the Alpha-Tocopherol Beta
      Carotene Cancer Prevention Study cohort. At baseline, serum HDL-C and total
      cholesterol concentrations from fasting blood, information on diet and lifestyle,
      and direct measurements of height, weight, and blood pressure were obtained from
      27,074 healthy male smokers of ages 50 to 69 years. Cox proportional hazards
      models with age as underlying time metric was used to estimate relative risks
      (RR) and 95% confidence intervals (95% CI). We found no association between total
      or non-HDL cholesterol and the 201 incident NHL cases ascertained during the
      follow-up (1985-2002), but observed an inverse association between HDL-C and NHL,
      which changed with length of follow-up. High HDL-C was associated with lower risk
      of all NHL during the first 10 years (n = 148; RR for 5th versus 1st quintile,
      0.35; 95% CI, 0.19-0.62; P(trend) < 0.0001), but not with diagnoses during later
      follow-up (n = 53; RR, 1.31; 95% CI, 0.55-3.10). The inverse association was
      similar for NHL subtypes and was not modified by obesity, blood pressure,
      physical activity, or alcohol intake, but seemed to be stronger in men with lower
      duration of smoking (P(interaction) = 0.06). Our findings implicate HDL-C as a
      preclinical indicator of NHL and warrant further prospective investigations for
      its etiologic contribution.

PMID- 17522389
TI  - Loss of betaglycan expression in ovarian cancer: role in motility and invasion.
AB  - The transforming growth factor-beta (TGF-beta) superfamily members, TGF-beta,
      activin, and inhibin, all have prominent roles in regulating normal ovarian
      function. Betaglycan, or the type III TGF-beta receptor, is a coreceptor that
      regulates TGF-beta, activin, and inhibin signaling. Here, we show that betaglycan
      expression is frequently decreased or lost in epithelial derived ovarian cancer
      at both the mRNA and protein level, with the degree of loss correlating with
      tumor grade. Treatment of ovarian cancer cell lines with the methyltransferase
      inhibitor 5-aza-2-deoxycytidine and the histone deacetylase inhibitor
      trichostatin A resulted in significant synergistic induction of betaglycan
      message levels and increased betaglycan protein expression, indicating that
      epigenetic silencing may play a role in the loss of betaglycan expression
      observed in ovarian cancer. Although restoring betaglycan expression in Ovca429
      ovarian cancer cells is not sufficient to restore TGF-beta-mediated inhibition of
      proliferation, betaglycan significantly inhibits ovarian cancer cell motility and
      invasiveness. Furthermore, betaglycan specifically enhances the antimigratory
      effects of inhibin and the ability of inhibin to repress matrix metalloproteinase
      levels in these cells. These results show, for the first time, epigenetic
      regulation of betaglycan expression in ovarian cancer, and a novel role for
      betaglycan in regulating ovarian cancer motility and invasiveness.

PMID- 17522392
TI  - Serum levels of soluble form of receptor for advanced glycation end products
      (sRAGE) may reflect tissue RAGE expression in diabetes.

PMID- 17522394
TI  - Apolipoprotein A-V genetic variation and plasma lipoprotein response to fibrates.

PMID- 17522395
TI  - LDL cholesteryl oleate: a biomarker for atherosclerosis?

PMID- 17522396
TI  - Videos in clinical medicine. Central venous catheterization.

PMID- 17522397
TI  - Images in clinical medicine. A complication of central venous catheterization.

PMID- 17522398
TI  - Aspirin and the risk of colorectal cancer in relation to the expression of COX-2.
AB  - BACKGROUND: Regular use of aspirin reduces the risk of a colorectal neoplasm, but
      the mechanism by which aspirin affects carcinogenesis in the colon is not well
      understood. METHODS: We estimated cyclooxygenase-2 (COX-2) expression by
      immunohistochemical assay of sections from paraffin-embedded colorectal-cancer
      specimens from two large cohorts of participants who provided data on aspirin use
      from a questionnaire every 2 years. We applied Cox regression to a competing
      risks analysis to compare the effects of aspirin use on the relative risk of
      colorectal cancer in relation to the expression of COX-2 in the tumor. RESULTS:
      During 2,446,431 person-years of follow-up of 82,911 women and 47,363 men, we
      found 636 incident colorectal cancers that were accessible for determination of
      COX-2 expression. Of the tumors, 423 (67%) had moderate or strong COX-2
      expression. The effect of aspirin use differed significantly in relation to COX-2
      expression (P for heterogeneity=0.02). Regular aspirin use conferred a
      significant reduction in the risk of colorectal cancers that overexpressed COX-2
      (multivariate relative risk, 0.64; 95% confidence interval [CI], 0.52 to 0.78),
      whereas regular aspirin use had no influence on tumors with weak or absent
      expression of COX-2 (multivariate relative risk, 0.96; 95% CI, 0.73 to 1.26). The
      age-standardized incidence rate for cancers that overexpressed COX-2 was 37 per
      100,000 person-years among regular aspirin users, as compared with 56 per 100,000
      person-years among those who did not use aspirin regularly; in contrast, the rate
      for cancers with weak or absent COX-2 expression was 27 per 100,000 person-years
      among regular aspirin users, as compared with 28 per 100,000 person-years among
      nonregular aspirin users. CONCLUSIONS: Regular use of aspirin appears to reduce
      the risk of colorectal cancers that overexpress COX-2 but not the risk of
      colorectal cancers with weak or absent expression of COX-2.

PMID- 17522399
TI  - Advanced life support for out-of-hospital respiratory distress.
AB  - BACKGROUND: Respiratory distress is a common symptom of patients transported to
      hospitals by emergency medical services (EMS) personnel. The benefit of advanced
      life support for such patients has not been established. METHODS: The Ontario
      Prehospital Advanced Life Support (OPALS) Study was a controlled clinical trial
      that was conducted in 15 cities before and after the implementation of a program
      to provide advanced life support for patients with out-of-hospital respiratory
      distress. Paramedics were trained in standard advanced life support, including
      endotracheal intubation and the administration of intravenous drugs. RESULTS: The
      clinical characteristics of the 8138 patients in the two phases of the study were
      similar. During the first phase, no patients were treated by paramedics trained
      in advanced life support; during the second phase, 56.6% of patients received
      this treatment. Endotracheal intubation was performed in 1.4% of the patients,
      and intravenous drugs were administered to 15.0% during the second phase. This
      phase of the study was also marked by a substantial increase in the use of
      nebulized salbutamol and sublingual nitroglycerin for the relief of symptoms. The
      rate of death among all patients decreased significantly, from 14.3% to 12.4%
      (absolute difference, 1.9%; 95% confidence interval [CI], 0.4 to 3.4; P=0.01)
      from the basic-life-support phase to the advanced-life-support phase (adjusted
      odds ratio, 1.3; 95% CI, 1.1 to 1.5). CONCLUSIONS: The addition of a specific
      regimen of out-of-hospital advanced-life-support interventions to an existing EMS
      system that provides basic life support was associated with a decrease in the
      rate of death of 1.9 percentage points among patients with respiratory distress.

PMID- 17522400
TI  - Level and volume of neonatal intensive care and mortality in very-low-birth
      weight infants.
AB  - BACKGROUND: There has been a large increase in both the number of neonatal
      intensive care units (NICUs) in community hospitals and the complexity of the
      cases treated in these units. We examined differences in neonatal mortality among
      infants with very low birth weight (below 1500 g) among NICUs with various levels
      of care and different volumes of very-low-birth-weight infants. METHODS: We
      linked birth certificates, hospital discharge abstracts (including interhospital
      transfers), and fetal and infant death certificates to assess neonatal mortality
      rates among 48,237 very-low-birth-weight infants who were born in California
      hospitals between 1991 and 2000. RESULTS: Mortality rates among very-low-birth
      weight infants varied according to both the volume of patients and the level of
      care at the delivery hospital. The effect of volume also varied according to the
      level of care. As compared with a high level of care and a high volume of very
      low-birth-weight infants (more than 100 per year), lower levels of care and lower
      volumes (except for those of two small groups of hospitals) were associated with
      significantly higher odds ratios for death, ranging from 1.19 (95% confidence
      interval [CI], 1.04 to 1.37) to 2.72 (95% CI, 2.37 to 3.12). Less than one
      quarter of very-low-birth-weight deliveries occurred in facilities with NICUs
      that offered a high level of care and had a high volume, but 92% of very-low
      birth-weight deliveries occurred in urban areas with more than 100 such
      deliveries. CONCLUSIONS: Mortality among very-low-birth-weight infants was lowest
      for deliveries that occurred in hospitals with NICUs that had both a high level
      of care and a high volume of such patients. Our results suggest that increased
      use of such facilities might reduce mortality among very-low-birth-weight
      infants.

PMID- 17522401
TI  - Bariatric surgery for morbid obesity.

PMID- 17522402
TI  - Images in clinical medicine. The sign of Leser-Trelat.

PMID- 17522403
TI  - Case records of the Massachusetts General Hospital. Case 16-2007. A 61-year-old
      man with a mediastinal mass.

PMID- 17522404
TI  - Aspirin and colon cancer--targeting prevention?

PMID- 17522405
TI  - A healthy tan?

PMID- 17522406
TI  - Prevention of death in COPD.

PMID- 17522407
TI  - Posaconazole prophylaxis in hematologic cancer.

PMID- 17522408
TI  - Treatment of symptomatic uterine fibroids.

PMID- 17522409
TI  - New treatments for diabetes.

PMID- 17522410
TI  - Monoclonal gammopathy of undetermined significance.

PMID- 17522411
TI  - Pulmonary-valve endocarditis.

PMID- 17522412
TI  - Quantitative glycomics of human whole serum glycoproteins based on the
      standardized protocol for liberating N-glycans.
AB  - Global glycomics of human whole serum glycoproteins appears to be an innovative
      and comprehensive approach to identify surrogate non-invasive biomarkers for
      various diseases. Despite the fact that quantitative glycomics is premised on
      highly efficient and reproducible oligosaccharide liberation from human serum
      glycoproteins, it should be noted that there is no validated protocol for which
      deglycosylation efficiency is proven to be quantitative. To establish a standard
      procedure to evaluate N-glycan release from whole human serum glycoproteins by
      peptide-N-glycosidase F (PNGase F) treatment, we determined the efficiencies of
      major N-glycan liberation from serum glycoproteins in the presence of reducing
      agents, surfactants, protease treatment, or combinations of pretreatments prior
      to PNGase F digestion. We show that de-N-glycosylation efficiency differed
      significantly depending on the condition used, indicative of the importance of a
      standardized protocol for the accumulation and comparison of glycomics data.
      Maximal de-N-glycosylation was achieved when serum was subjected to reductive
      alkylation in the presence of 2-hydroxyl-3-sulfopropyl dodecanoate, a surfactant
      used for solubilizing proteins, or related analogues, followed by tryptic
      digestion prior to PNGase F treatment. An optimized de-N-glycosylation protocol
      permitted relative and absolute quantitation of up to 34 major N-glycans present
      in serum glycoproteins of normal subjects for the first time. Moreover PNGase F
      catalyzed de-N-glycosylation of whole serum glycoproteins was characterized
      kinetically, allowing accurate simulation of PNGase F-catalyzed de-N
      glycosylation required for clinical glycomics using human serum samples. The
      results of the current study may provide a firm basis to identify new diagnostic
      markers based on serum glycomics analysis.

PMID- 17522413
TI  - A qualitative study of a nutrition working group.
AB  - The Behavioral Change Consortium (BCC) Nutrition Workgroup (NWG) is a
      multidisciplinary collaboration of representatives from BCC sites and federal
      agencies. Its mission is to improve measurement of dietary variables. This
      article presents findings from a qualitative study of perceived effectiveness of
      the workgroup collaboration. Twelve in-depth interviews were conducted and
      examined for common themes using the constant comparison method. Themes
      contributing to perceived effectiveness included: funding and additional
      resources; invested, committed, and collegial members; strong leadership, clearly
      articulated goals, and regular communication. Influences seen as reducing
      effectiveness were: distance, disparate nature of the studies, limited time, and
      problems associated with starting collaboration after the primary studies had
      begun data collection. NWG members felt that the workgroup would continue to be
      successful; however, there were concerns about responsibility for writing and
      authorship of manuscripts and the need for continued funding to ensure full
      participation and productivity.

PMID- 17522414
TI  - Gonadotropin therapy for infertile men with hypogonadotropic hypogonadism.

PMID- 17522415
TI  - One semen sample or 2? Insights from a study of fertile men.

PMID- 17522416
TI  - L859F mutation in androgen receptor gene results in complete loss of androgen
      binding to the receptor.
AB  - Androgens drive male secondary sexual differentiation and maturation. Mutations
      in the androgen receptor (AR) gene cause an array of abnormal sex differentiation
      phenotypes in humans, ranging from mild through partial to complete androgen
      insensitivity. Earlier, we reported a C3693T missense mutation in the AR gene in
      a familial case of complete androgen insensitivity syndrome (CAIS), resulting in
      the replacement of a highly conserved leucine residue with phenylalanine (L859F)
      in ligand-binding domain (LBD) of the receptor. In silico analysis and the
      information from the crystal structure of AR-LBD indicated that the residue L859,
      located in helix 10 of AR protein, plays a significant role in overall
      architecture of the ligand-binding pocket. From this information we anticipated
      that the mutation might have resulted in the loss of the ligand binding to the
      receptor. In the present study, we have conducted the in vitro functional assays
      for this mutation. The mutation resulted in highly significant loss of the ligand
      binding to the receptor. The loss of ligand binding and subsequent AR function
      was confirmed by the transactivation assay, in which we observed very little
      activation of the reporter gene expressed under the control of the ligand-AR
      complex.

PMID- 17522417
TI  - The response of the corporal tissue and cavernosus muscles to urethral
      stimulation: an effect of penile buffeting of the vaginal introitus.
AB  - We investigated the hypothesis that urethral stimulation in humans induces sexual
      response in the form of activation of the corporal tissue and cavernosus muscles
      through a reflex mechanism. Electromyographic activity of corpora cavernosa (CC),
      corpus spongiosum (CS), bulbocavernosus (BCM), and ischiocavernosus (ICM) muscles
      was recorded in 43 healthy volunteers (24 men, 19 women; age, 37.7 +/- 8.2 years)
      during urethral stimulation. The tests were repeated after individual
      anesthetization of urethra, CC, CS, BCM, and ICM. During stimulation of the
      distal urethra, slow wave variables of CC and CS decreased while motor unit
      action potentials of BCM and ICM increased. Urethral stimulation after individual
      anesthetization of urethra, CC, CS, BCM, and ICM did not effect significant
      changes in these structures, but saline administration did. Diminished
      electromyographic activity of CC and CS with increased activity of BCM and ICM
      during distal urethral stimulation presumably denotes sinusoidal muscle
      relaxation of CC and CS and cavernosus muscles' contraction. Sinusoidal muscle
      relaxation and contraction of cavernosus muscles upon distal urethral stimulation
      are suggested to be mediated through a reflex that we call the "urethro
      corporocavernosal reflex." Sinusoidal and cavernosus muscles' response during
      coitus appears to effect a degree of tumescence for both male and female
      partners.

PMID- 17522418
TI  - Recombinant adenovirus mediated prostate-specific enzyme pro-drug gene therapy
      regulated by prostate-specific membrane antigen (PSMA) enhancer/promoter.
AB  - Gene directed enzyme pro-drug therapy (GDEPT) is one of the adjuvant therapeutic
      regimens for advanced prostate adenocarcinoma, and this research intended to
      explore how to apply targeting therapy of prostate adenocarcinoma under the
      mediation of a promoter/enhancer of prostate-specific membrane antigen (PSMA(EP))
      as a specific regulatory element. Recombinant adenoviruses (Ad-PSMA(E-P)-enhanced
      green fluorescent protein [EGFP], Ad-CMV-EGFP, Ad-PSMA(E-P)-CD, and Ad-CMV-CD)
      were constructed and could express cytosine deaminase (CD) or the EGFP reporter
      gene driven by a PSMA(EP) or cytomegalovirus (CMV) promoter. LNCaP, CL-1, MCF-7,
      and A549 were infected with CD-produced recombinant adenoviruses and treated with
      pro-drug 5-fluorocytosine (5-FC) in vivo and vitro; then, the growth inhibition
      of the cells and the cell cycle variation were assessed by an [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and flow
      cytometry. Growth suppression of the xenograft tumor was also adopted to evaluate
      the efficiency of the suicide system. Morphologic changes after treatment in vivo
      were assessed with hematoxylin and eosin staining. In the 4 examined cancer cell
      lines, PSMA-positive prostate cancer cells LNCap and CL-1 were exclusively
      sensitive to the Ad-PSMA(E-P)-CD/5-FC system. The S phase of cell cycle arrest
      was thought to be involved in the cytotoxicity of 5-fluorouracil (5-FU) converted
      from 5-FC by CD. CL-1 implanted Athymic BALB/c mice showed growth inhibition of
      tumors when they were treated with the Ad-PSMA(E-P)-CD/5-FC system without
      systemic conversion toxicity. The PSMA-based, CD-produced adenovirus, deserving
      further investigation in the future, might be a good candidate for targeting gene
      therapy of prostate adenocarcinoma.

PMID- 17522419
TI  - Effects of long-term castration on the smooth muscle cell phenotype of the rat
      ventral prostate.
AB  - Smooth muscle (SM) is an important component of the prostatic stroma. We
      previously showed that, despite extensive morphologic changes, smooth muscle
      cells (SMCs) of the rat ventral prostate preserve some differentiation markers 21
      days after castration. In the present study, we investigated whether the
      expression of SMC markers is preserved in the rat ventral prostate after long
      term castration. Adult Wistar rats were castrated and sacrificed 100 days after
      surgery. The ventral prostates were processed for histology, stereology,
      immunocytochemistry (SM alpha-actin and SM-myosin heavy chain [MHC]),
      transmission electron microscopy (TEM), and reverse transcription polymerase
      chain reaction (smoothelin, sm22, and calponin). The prostates of castrated rats
      showed significant weight reduction, corresponding to only 5.6% of the control.
      Stereology showed that SMCs occupied the same proportion of the prostate volume
      but suffered a significant reduction in absolute volume (5.5% of control). The
      SMCs were retracted and showed spinous outlines. TEM revealed the presence of an
      abundant myofibrillar component, dense plaques, and an external lamina in these
      cells. SMCs were reactive to antibodies against SM alpha-actin and SM-MHC and
      expressed mRNA for smoothelin, sm22, and calponin. The results confirmed that rat
      prostatic SMCs are affected by androgen deprivation. Although showing marked
      phenotypic changes, these cells expressed SMC markers at the protein (SM alpha
      actin and SM-MHC) and mRNA (smoothelin, sm22, and calponin) levels. These
      observations support the idea that SMCs may modulate their phenotypes
      (contractile vs synthetic) without changing their differentiation states.

PMID- 17522420
TI  - Structural alterations of epididymal epithelial cells in cathepsin A-deficient
      mice affect the blood-epididymal barrier and lead to altered sperm motility.
AB  - Past studies have shown that the epithelial lining of the epididymis in adult
      mice deficient in protective protein cathepsin A (PPCA -/-) becomes swollen and
      vacuolated as a result of an accumulation of pale lysosomes, some very large, in
      addition to the presence of an abundance of macrophages infiltrating the
      intertubular spaces. The purpose of this study was to assess the integrity of the
      epididymal epithelial-blood barrier in these altered mice by characterizing the
      distribution of claudins (Cldns) and the leakiness of tight junctions to
      lanthanum nitrate. A second goal was to characterize sperm motility behavior in
      PPCA -/- mice using computer-assisted sperm analyses (CASA). The results
      indicated that lanthanum nitrate penetrated apical junctional complexes between
      adjacent epithelial cells and entered the epididymal lumen in PPCA -/- mice but
      not in control PPCA +/+ mice. Immunostaining for Cldns 1, 3, 8, and 10 revealed
      unique patterns of expression based on cell type and region specificity in PPCA
      +/+ mice, which were much different in PPCA -/- mice. PPCA -/- mice showed
      reduced intensities of immunoreactions, complete absence of immunoreactions, and
      appearance of atypical cytoplasmic immunoreactions. CASA indicated that sperm
      counts in the PPCA -/- mice were 70% reduced, and among other problems, there was
      a fourfold higher percentage of static sperm in PPCA -/- mice compared with
      controls. These results suggest that PPCA deficiency causes structural changes to
      the blood-epididymal barrier as evidenced by lanthanum nitrate and Cldns
      expression that affects the luminal environment of the epididymis, resulting in
      altered sperm motility.

PMID- 17522421
TI  - The long dark night of the sports medicine soul.

PMID- 17522428
TI  - Association of progesterone receptor gene polymorphism (PROGINS) with
      endometriosis, uterine fibroids and breast cancer.
AB  - Endometriosis, uterine fibroids and breast cancer are female health disorders
      associated with a great deal of morbidity. Since all these disorders are hormone
      responsive, our present study has been carried out to identify the association of
      306bp Alu insertion polymorphism in intron 7 of progesterone receptor gene
      (PROGINS). DNA was isolated from the blood samples of 445 Asian Indian women,
      which included 100 endometriosis, 80 fibroids and 157 cases of breast cancer
      along with 108 age matched normal healthy women as controls. PROGINS polymorphism
      was assessed by PCR followed by agarose gel electrophoresis. Results showed that
      T2 allele frequency is 5%, 10% and 14.6% in endometriosis, uterine fibroids and
      breast cancer, as compared to 5.5% in controls. This indicates that PROGINS can
      be considered as a predisposing risk marker for breast cancer but not for
      endometriosis and uterine fibroids.

PMID- 17522429
TI  - Risk factors for hepatocellular carcinoma may impair the performance of
      biomarkers: a comparison of AFP, DCP, and AFP-L3.
AB  - Current surveillance strategies for hepatocellular carcinoma (HCC) are applied
      uniformly in patients with cirrhosis, regardless of their cancer risk. The aim of
      this study was to compare the performance characteristics of the biomarkers alpha
      fetoprotein (AFP), des-gamma carboxyprothrombin (DCP), and lectin-bound AFP (AFP
      L3) in the diagnosis of HCC, and to determine the effect of risk factors for HCC
      on test performance. Eighty-four patients with HCC and 169 patients with
      cirrhosis were enrolled and their serum analyzed for total AFP, AFP-L3 and DCP.
      Receiver-operating characteristic (ROC) curves were constructed to determine the
      performance characteristics. DCP was significantly better than total AFP or AFP
      L3 in differentiating HCC from cirrhosis, with a sensitivity of 86% and
      specificity of 93%. When subjects were divided into two groups by their risk for
      HCC, all 3 markers had a lower sensitivity and area under the ROC curve in the
      high-risk group compared to the low-risk group. In conclusion, DCP has the best
      performance characteristics of all 3 serum markers for the diagnosis of HCC.
      Serum biomarkers may be less sensitive and specific in the highest risk patients.

PMID- 17522430
TI  - Polymorphisms in TRAIL receptor genes and risk of breast cancer in Spanish women.
AB  - TRAIL is a potent inducer of apoptosis in malignant but not in normal cells.
      TRAIL binds to the proapoptotic death receptor DR4 and DR5 as well as to the
      decoy receptors DcR1 and DcR2. To evaluate the involvement of TRAIL receptor
      genes in breast cancer, we carried out a case-control study of eight selected
      polymorphisms in a large sample of Spanish women. Three of the eight selected
      SNPs (626G/C and 1322G/A in DR4 and 2699A/G in DcR2) showed some evidence of
      different genotype distributions in a random selection of 535 cases and 480
      controls and were therefore studied in our entire sample (1008 cases and 768
      controls). For the two DR4 polymorphisms, no differences in genotype or haplotype
      distribution were found between cases and controls. Interestingly, allele 2699G
      in the decoy receptor DcR2 appears associated with reduced breast cancer risk
      (P=0.05). Given that it is located in the 3' UTR, its effect might be related to
      DcR2 mRNA instability, or linkage disequilibrium with a functional variant
      residing in either DcR2 or neighbouring genes. A decreased efficiency of DcR2 to
      work as decoy receptor for TRAIL, would facilitate the apoptotic pathway in cells
      at risk.

PMID- 17522431
TI  - Prediction of lung cancer using volatile biomarkers in breath.
AB  - BACKGROUND: Normal metabolism generates several volatile organic compounds (VOCs)
      that are excreted in the breath (e.g. alkanes). In patients with lung cancer,
      induction of high-risk cytochrome p450 genotypes may accelerate catabolism of
      these VOCs, so that their altered abundance in breath may provide biomarkers of
      lung cancer. METHODS: VOCs in 1.0 L alveolar breath were analyzed in 193 subjects
      with primary lung cancer and 211 controls with a negative chest CT. Subjects were
      randomly assigned to a training set or to a prediction set in a 2:1 split. A
      fuzzy logic model of breath biomarkers of lung cancer was constructed in the
      training set and then tested in subjects in the prediction set by generating
      their typicality scores for lung cancer. RESULTS: Mean typicality scores
      employing a 16 VOC model were significantly higher in lung cancer patients than
      in the control group (p<0.0001 in all TNM stages). The model predicted primary
      lung cancer with 84.6% sensitivity, 80.0% specificity, and 0.88 area under curve
      (AUC) of the receiver operating characteristic (ROC) curve. Predictive accuracy
      was similar in TNM stages 1 through 4, and was not affected by current or former
      tobacco smoking. The predictive model achieved near-maximal performance with six
      breath VOCs, and was progressively degraded by random classifiers. Predictions
      with fuzzy logic were consistently superior to multilinear analysis. If applied
      to a population with 2% prevalence of lung cancer, a screening breath test would
      have a negative predictive value of 0.985 and a positive predictive value of
      0.163 (true positive rate =0.277, false positive rate =0.029). CONCLUSIONS: A two
      minute breath test predicted lung cancer with accuracy comparable to screening CT
      of chest. The accuracy of the test was not affected by TNM stage of disease or
      tobacco smoking. Alterations in breath VOCs in lung cancer were consistent with a
      non-linear pathophysiologic process, such as an off-on switch controlling high
      risk cytochrome p450 activity. Further research is needed to determine if
      detection of lung cancer with this test will reduce mortality.

PMID- 17522432
TI  - Bone morphogenetic protein 7 (BMP7) expression is a potential novel prognostic
      marker for recurrence in patients with primary melanoma.
AB  - The purpose of this study was to investigate whether protein expression of bone
      morphogenetic protein 7 (BMP7) is associated with clinico-pathologic
      characteristics in benign and malignant melanocytic skin tumors. Tissue
      microarrays (TMAs) were used to analyze BMP7 expression and the Ki-67 labeling
      index immunohistochemically. Expression was scored semi quantitatively (0-2+).
      BMP7 protein expression of any intensity (1+-2+) was detected in 50.2% (153/305)
      of informative cases. In general, BMP7 expression was significantly induced in
      malignant melanomas (P< 0.001) and melanoma metastases (P< 0.001), compared to
      benign nevi. Additionally, expression of BMP7 in primary melanomas was associated
      with Ki-67 labeling index > 5% suggesting that induction of BMP7 expression is
      associated with proliferation (P=0.028). None of the other clinical and
      histological factors analyzed was significantly related to BMP7 expression.
      Interestingly, lymph node metastases demonstrated a significantly higher BMP7
      expression compared to skin metastases (P<0.01). Strong BMP7 expression (score
      2+) was significantly associated with shorter tumor recurrence (P< 0.05). In
      summary, induction of BMP7 expression is frequent in melanomas and may serve as a
      novel prognostic marker of progression in melanoma patients.

PMID- 17522433
TI  - Generation and optimization of human antagonistic antibodies against TIMP-1 as
      potential therapeutic agents in fibrotic diseases.
AB  - Impaired matrix metalloproteinase 1 (MMP-1) function, as result of the expression
      of increased levels of tissue inhibitor of metalloproteinase 1 (TIMP-1), plays an
      important role in the pathopysiolgical mechanism of fibrosis. In a recently
      performed clinically relevant rat animal model of established liver fibrosis, it
      could be shown, that blocking the interaction between the metalloproteinase and
      its inhibitor has beneficial effects in vivo. The rat TIMP-1 specific
      antagonistic antibody used in this study was derived from a human combinatorial
      antibody library (HuCAL) and blocks the interaction between rat TIMP-1 and MMP
      13, the rat homologue of human MMP-1. We here describe the utilization of the
      same antibody source to generate fully human antibodies against human TIMP-1
      which could be potential candidates for a therapy of fibrosis in man. In order to
      develop a highly potent antagonist of TIMP-1 action, antibodies isolated from the
      library were subjected to a number of different in vitro affinity maturation
      strategies. By these means, affinity and potency were improved by a factor of 87
      and 65 fold, respectively, resulting in a valuable human therapeutic antibody
      candidate with a monovalent affinity of 150 pM and a potency for in vitro
      inhibition of TIMP-1/MMP-1 interaction of 200 pM.

PMID- 17522434
TI  - Conversion of a mouse Fab into a whole humanized IgG antibody for detecting
      botulinum toxin.
AB  - Antibodies serve as the gold standard in most immunodiagnostic assays. Recent
      advances in recombinant DNA technology have offered the production of antibody
      fragments or Fabs as promising alternatives. However, the lack of the Fc region
      of the antibody can be difficult in many standard diagnostic platforms. Therefore
      we sought to convert a murine Fab into a whole humanized IgG. The variable
      regions from an anti-botulinum Fab were cloned into human IgG heavy and light
      chain vectors and produced in myeloma cells. Purified humanized IgG demonstrated
      conversion to human IgG with no traces of mouse Fab as determined by Western blot
      analysis. In addition, the humanized IgG performed better as both a detection and
      capture reagent in an ELISA format and detected the botulinum toxoid at a lower
      concentration than the parental murine Fab. This technique offers the ability to
      convert various species of antibodies or antibody fragments into humanized
      antibodies with improved characteristics in immunodiagnostic assays, for use as
      human controls in serological assays, or for possible therapeutic benefit.

PMID- 17522435
TI  - A simple and practical agglutination assay for the detection of human anti-mouse
      antibodies.
AB  - BACKGROUND AND OBJECTIVES: Human anti-mouse antibodies (HAMAs) are relatively
      common in human serum and may interfere with therapeutic and diagnostic mouse
      monoclonal antibodies (MoAbs). We developed a simple particle agglutination test
      (PaGIA) for the detection of HAMAs. DESIGN AND METHODS: Red-dyed high density
      particles were coated with monoclonal mouse IgG. These particles were incubated
      in the reaction chamber of a gel-card together with serum samples obtained from
      healthy blood donors (n=32), and patients with clinically proven autoimmune
      thrombocytopenia (AITP; n=26). Positive reactions were defined by a layer of
      particles on top of the gel or agglutinated particles dispersed throughout the
      gel matrix. Furthermore, MoAb-coated particles were subjected to flow cytometry
      and the results were compared with the new HAMA PaGIA. RESULTS: HAMAs were
      detectable in 33% of serum samples tested (n=58). Results from flow cytometric
      analysis revealed a high parallel to those obtained by the PaGIA. Interestingly,
      we observed an increased incidence of HAMAs in AITP patients (42%) compared to
      healthy blood donors (26%). INTERPRETATION AND CONCLUSION: The new HAMA PaGIA
      allows a specific and easy, rapid detection of HAMAs and is suitable for large
      scale testing.

PMID- 17522436
TI  - Renewal of EBV-hybridoma method: efficient generation of recombinant fully human
      neutralizing IgG antibodies specific for tetanus toxin by use of tetroma cells.
AB  - We have generated tetroma cell lines by the fusion of newly developed parental
      6JC5.2 cells with a human B cell line, which was transformed with Epstein-Barr
      virus (EBV) and enriched with antibody-forming cells that produce neutralizing
      antibodies to tetanus toxin (TT) by a limiting dilution method using IL-6. The
      resultant two tetroma cell lines stably produced different monoclonal antibodies
      (mAbs), TT1 (IgG1.lambda) and TT2 (IgG4.kappa) reactive with TT after three-times
      consecutive cell cloning. Although weak to almost nonexistent neutralizing
      activities against TT were detected in TT1 and TT2 mAbs, respectively, mixing of
      them resulted in a dramatic increase in the neutralizing activity and complete
      protection from the toxin was observed in vivo. Moreover, functional
      immunoglobulin (Ig) genes were cloned from at least 10 cells in the first cloning
      step of tetromas after the cell fusion. None of the endogenous Ig genes, derived
      from the parental cell that hinders functional Ig gene cloning, was amplified. In
      addition, the EBV genome derived from the B cells was eliminated from the
      antibody producing tetroma lines. This classical but revised EBV-hybridoma method
      using fusion partner 6JC5.2 may become one alternative method for production of
      fully human antibodies useful for prevention and treatment of infectious diseases
      and cancer.

PMID- 17522437
TI  - A rapid method for generating and characterizing anti-variable region monoclonal
      antibodies.
AB  - The generation of anti-variable region monoclonal antibodies (mAbs) against
      therapeutic antibodies is essential in the pharmacokinetic/pharmacodynamic
      (PK/PD) assessments of the drugs in clinical study samples. Sandwich EIA and
      other methods are typically employed to achieve sensitivity and selectivity for
      the PK/PD analyses. These assays usually require generation of mAb reagents that
      bind specifically to the therapeutic mAb candidate in non-competing pair
      combinations. Thus, large panels of anti-variable region mAbs must be generated
      in an expeditious manner to increase the probability of success. Previously, we
      described a novel immunization method using type 1 interferons (IFNs) coupled
      with an agonistic anti-CD40 mAb to drive immune responses (Staquet et al., Human
      Antibodies 15 (2006), 61-69). This protocol allows for rapid and robust
      generation of large panels of anti-variable region mAbs. In order to quickly
      characterize and efficiently identify optimal anti-variable region antibody pairs
      early in the hybridoma process using crude supernatants, an inexpensive, high
      throughput ELISA method was developed. The ability to rapidly identify
      appropriate mAb pairs will save resources by eliminating the time-consuming and
      laborious process of subcloning irrelevant hybridomas.

PMID- 17522438
TI  - Free radicals and cell signaling in Alzheimer's disease.

PMID- 17522439
TI  - Signal transduction cascades associated with oxidative stress in Alzheimer's
      disease.
AB  - It has now been established through multiple lines of evidence that oxidative
      stress is an early event in Alzheimer's disease, occurring prior to the canonical
      cytopathology. Thus, oxidative stress likely plays a key pathogenic role in the
      disease and is clearly involved in the cell loss and other neuropathology
      associated with Alzheimer's disease as demonstrated by the large number of
      metabolic signs of oxidative stress and by markers of oxidative damage. One
      puzzling observation, however, is that oxidative damage decreases with disease
      progression, such that levels of markers of rapidly formed oxidative damage,
      which are initially elevated, decrease as the disease progresses to advanced
      Alzheimer's disease. This finding indicates that reactive oxygen species not only
      cause damage to cellular structures but also provoke cellular responses, such as
      the compensatory upregulation of antioxidant enzymes found in vulnerable neurons
      in Alzheimer's disease. Not surprisingly, stress-activated protein kinase
      pathways, which are activated by oxidative stress, are extensively activated
      during Alzheimer's disease. In this review, we present the evidence of oxidative
      stress and compensatory responses that occur in Alzheimer's disease with a
      particular focus on the roles and mechanism of activation of stress-activated
      protein kinase pathways.

PMID- 17522440
TI  - Proteomics analysis of the Alzheimer's disease hippocampal proteome.
AB  - Alzheimer's disease (AD) is characterized by the presence of intracellular
      neurofibrillary tangles (NFT), extracellular senile plaques (SP), and synaptic
      loss. The hippocampus is a region that plays an important role in memory and
      cognitive function, and it is severely affected in AD. The levels of proteins in
      the hippocampus may provide a better understanding of the pathological changes
      known. In the present study we used two-dimensional gel electrophoresis and mass
      spectrometry techniques to determine changes in protein levels in AD and control
      hippocampus. We identified 18 proteins with altered protein levels that are
      involved in regulating different cellular functions. Protein levels were found to
      be significantly decreased for peptidyl prolyl cis/trans-isomerase (Pin 1) (0.6
      fold compared to control, p<0.03), dihydropyrimidinase-like protein 2 (DRP-2)
      (0.74-fold compared to control, p<0.02), phosphoglycerate mutase 1 (PGM1) (0.7
      fold compared to control, p<0.01), beta-tubulin (0.34-fold compared to control,
      p<0.01), and aldolase A (0.87-fold compared to control, p<0.0002), whereas the
      protein levels were found to be significantly increased for enolase (1.35-fold
      compared to control, p<0.05), ubiquitin carboxyl terminal hydrolase L-1 (UCH L1)
      (1.31-fold compared to control, p<0.02), triosephosphate isomerase (TPI) (1.38
      fold compared to control, p<0.05), carbonic anhydrase II (CAH-II) (1.24-fold
      compared to control, p=0.05), heat shock protein 70 (1.14-fold compared to
      control, p<0.03), fructose bisphosphate aldolase (1.38-fold compared to control,
      p<0.05), ferritin heavy chain (1.23-fold compared to control, p=0.05), 2',3'
      cyclic nucleotide 3' phosphodiestrase (CNPase) (1.12-fold compared to control,
      p<0.02), peroxiredoxin II (1.39-fold compared to control, p<0.05), and adenylate
      kinase I (1.19-fold compared to control, p<0.03). We found 2 proteins spots that
      were identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). One of the
      spots showed a 1.28-fold increase in protein level compared to control (p<0.01),
      and the other spot showed a similar 1.26-fold increase in protein level compared
      to control (p<0.04). Thus, proteomics has provided knowledge of the levels of key
      proteins in AD brain. We discuss the functions regulated by these proteins with
      respect to AD pathology.

PMID- 17522441
TI  - Oxidized proteins in astrocytes generated in a hyperbaric atmosphere induce
      neuronal apoptosis.
AB  - In the present study, we investigated the influence of the oxidative damage to
      astrocytes on neuronal cell survival using cultures of rat cerebral astrocytes
      and neurons. The exposure of astrocytes to hyperbaric oxygen induced a time
      dependent apoptotic cell death, as observed by DNA ladder assessment. When
      astrocytes damaged by oxidative stress were cocultured with normal neurons from
      the cerebrum of a newborn rat, neuronal cell death was markedly induced, although
      normal astrocytes not subjected to hyperoxia cocultured with normal neurons
      showed no neuronal cell apoptosis. It was found that either the supernatant from
      the homogenate of astrocytes cultured in hyperbaric oxygen atmosphere or a
      protein mixture extracted from the supernatant induced neuronal cell death. The
      level of protein carbonyls, an index of protein oxidation analysis, in cultured
      astrocytes increased significantly with oxidative stress, and vitamin E inhibited
      the increase in the level of such oxidized proteins in astrocytes. Furthermore, a
      two-dimensional (2D) electrophoresis of a protein mixture extracted from the
      supernatant showed several changes in proteins. These results imply that reactive
      oxygen species (ROS) induced by oxidative stress attack astrocytes to induce
      oxidatively denatured proteins in the cells that act as a neurotoxic factor, and
      that vitamin E protects neurons by inhibiting astrocyte apoptosis caused by
      oxidative stress.

PMID- 17522442
TI  - Mitochondrial oxidant signalling in Alzheimer's disease.
AB  - The role of free radicals in Alzheimer disease pathophysiology has been
      appreciated for a long time. Originally, radicals were considered as causative of
      oxidative damage. More recently their role as signalling molecules in this, as
      well as in other fields of free radical biology, has been underscored.
      Mitochondria are both generators and targets of radical damage in aging. In this
      paper we review evidence that radicals generated in mitochondria in the presence
      of A beta are signals that trigger both the mitochondrial and the extra
      mitochondrial pathways of apoptosis. There are gender specific differences in
      mitochondrial A beta toxicity: mitochondria from young (but not from old) females
      appear to be protected. 17-beta Estradiol or phytoestrogens like genistein
      prevent the formation of oxidants by mitochondria and protect against
      mitochondrial A beta toxicity. Experiments reported here indicate that
      phytoestrogens might have a role in the prevention of Alzheimer's disease.

PMID- 17522443
TI  - The involvement of lipid radical cycles and the adenine nucleotide translocator
      in neurodegenerative diseases.
AB  - The major cause of neurodegenerative disorders, including mid- to late-life onset
      Alzheimer's Disease, is permanent oxidative stress in the brain. Polyunsaturated
      fatty acids (PUFA) and alpha-tocopherol (alpha-TOH) are the most oxygen-sensitive
      constituents of cells. The presence of alpha-TOH in biological membranes is
      required but not sufficient to protect them against lipid peroxidation. The data
      presented in this review consider the role of alpha-TOH and cytochrome b5 which
      permit operation of lipid-radical cycles and the participation of lipid-radical
      reactions in key processes occurring in the membrane. Analysis of role of these
      cycles in membrane bioenergetics led us to a model involving the adenine
      nucleotide translocator and ATP synthesis in brain mitochondria. This paper
      summarizes experimental evidence for oxidative and non-oxidative pathways of PUFA
      metabolism with respective intermediates, which could be relevant to elucidation
      of new mechanisms of neurodegenerative diseases. Lipid-radical reactions in
      membranes work as important component of normal cell metabolism. Discussion is
      focused on the consequences of ineffective electron transfer to peroxyl radicals
      (LOO.--> LOO-) and excessive oxidative pathway of PUFA metabolism (LOO.-->LOOH)
      with two reactive secondary products: malondialdehyde and methylglyoxal. Our
      future aim is to develop a more detailed model supplemented by the formation of
      lipofuscin and amyloid structures.

PMID- 17522444
TI  - The role of metals in the etiology of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most
      common cause of dementia, affecting millions of men and women worldwide. It is
      characterized by the accumulation of extracellular amyloid-beta (A beta) plaques
      and neurofibrillary tangles inside neurons and dystrophic neurons. Several risk
      factors are associated with the early onset and progression of the disease.
      Although the initiating molecular events are not entirely known, in recent years
      it has become evident that environmental and/or nutritional factors may play a
      causal, disruptive, and/or protective role in the development of AD. While a
      direct causal role for aluminum or other transition metals (copper, zinc, iron)
      in AD has not yet been definitively demonstrated, epidemiological evidence
      suggests that elevated levels of these metals in the brain may be linked to the
      development or progression of AD. This review summarizes studies which implicate
      a role for several metals in contributing to or causing AD.

PMID- 17522445
TI  - Nitric oxide and nitroxidative stress in Alzheimer's disease.
AB  - Nitric oxide is a signaling molecule produced by neurons and endothelial cells in
      the brain. NO is synthesized from L-arginine and oxygen by nitric oxide synthase:
      neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). The endothelial NO
      acts as a vasorelaxant in the vasculature and as a neurotransmitter when produced
      by neurons (under the pathological conditions of Alzheimer's disease). NO can be
      scavenged in a rapid reaction with superoxide (O2-) to generate peroxynitrite
      (ONOO-), with a half-life of < 1 s. ONOO- is a potent oxidant and the primary
      component of nitroxidative stress. At high concentrations (> 100 nM), ONOO- can
      undergo homolytic or heterolytic cleavage to produce NO2+, NO2, and OH., highly
      reactive oxidative species and secondary components of nitroxidative stress. The
      high nitroxidative stress can initiate a cascade of redox reactions which can
      trigger apoptosis and evoke cytotoxic effects on neurons and endothelial cells.
      This article reviews the functions of NO and the potential role of NO/O2-/ONOO-
      induced nitroxidative stress in neuronal and endothelial degeneration observed in
      Alzheimer's disease.

PMID- 17522446
TI  - Homocysteine and its derivatives as possible modulators of neuronal and non
      neuronal cell glutamate receptors in Alzheimer's disease.
AB  - Homocysteine (HC) and its derivatives may be involved in the etiology of
      Alzheimer's Disease (AD), although the precise mechanisms by which these
      compounds could cause cellular pathology are still unclear. Because interactions
      of HC with glutamate receptors have been implicated in AD, receptor-mediated
      effects of HC and homocysteic acid (HCA) on neurons and lymphocytes have been
      analyzed. Activation of glutamate receptors by these compounds has been shown to
      increase intracellular calcium and free radical levels in both types of cells,
      which may serve as a signal for development of apoptosis. Activation of group III
      metabotropic glutamate receptors stimulates, whereas activation of group I and
      group II metabotropic glutamate receptors prevent, the excitotoxic action of HC
      and HCA. These effects may contribute to the neuronal pathology and
      immunosenescence that occur in AD. It is proposed that selective agonists of
      metabotropic glutamate receptors that counter the effects of HC and its
      derivatives may be used for correction of neuronal and immune cell metabolism in
      vivo under the conditions of hyperhomocysteinemia, which can occur in AD.

PMID- 17522447
TI  - Could carnosine or related structures suppress Alzheimer's disease?
AB  - Reactive oxygen species, reactive nitrogen species, copper and zinc ions,
      glycating agents and reactive aldehydes, protein cross-linking and proteolytic
      dysfunction may all contribute to Alzheimer's disease (AD). Carnosine (beta
      alanyl-L-histidine) is a naturally-occurring, pluripotent, homeostatic agent. The
      olfactory lobe is normally enriched in carnosine and zinc. Loss of olfactory
      function and oxidative damage to olfactory tissue are early symptoms of AD.
      Amyloid peptide aggregates in AD brain are enriched in zinc ions. Carnosine can
      chelate zinc ions. Protein oxidation and glycation are integral components of the
      AD pathophysiology. Carnosine can suppress amyloid-beta peptide toxicity, inhibit
      production of oxygen free-radicals, scavenge hydroxyl radicals and reactive
      aldehydes, and suppresses protein glycation. Glycated protein accumulates in the
      cerebrospinal fluid (CSF) of AD patients. Homocarnosine levels in human CSF
      dramatically decline with age. CSF composition and turnover is controlled by the
      choroid plexus which possesses a specific transporter for carnosine and
      homocarnosine. Carnosine reacts with protein carbonyls and suppress the
      reactivity of glycated proteins. Carbonic anhydrase (CA) activity is diminished
      in AD patient brains. Administration of CA activators improves learning in
      animals. Carnosine is a CA activator. Protein cross-links (gamma-glutamyl-epsilon
      amino) are present in neurofibrillary tangles in AD brain. gamma-Glutamyl
      carnosine has been isolated from biological tissue. Carnosine stimulates vimentin
      expression in cultured human fibroblasts. The protease oxidised-protein-hydrolase
      is co-expressed with vimentin. Carnosine stimulates proteolysis in cultured
      myocytes and senescent cultured fibroblasts. These observations suggest that
      carnosine and related structures should be explored for therapeutic potential
      towards AD and other neurodegenerative disorders.

PMID- 17522448
TI  - Hypothesis: lifespan is regulated by chronomere DNA of the hypothalamus.
AB  - As the basis for the lifelong clock and as a primary cause of aging, a process of
      shortening of hypothetical perichromosomal DNA structures termed chronomeres is
      proposed in the CNS. The lifelong clock is regulated by the shortening of
      chronomere DNA in postmitotic neurons of the hypothalamus. Shortening of these
      DNA sequences occurs in humans on a monthly basis through a lunasensory system
      and is controlled by release of growth hormone discharged from the anterior
      pituitary directly into the hypothalamus via local blood vessels. In adults, this
      process is under control of the pineal gland. It is further proposed that
      different forms of Alzheimer's disease (AD) are caused by somatic and inherited
      deletions of chronomeres followed by a further abnormally accelerated decrease in
      their activity, resulting in failures of neurotrophic and neuroendocrinal
      activities and in various cellular imbalances. In this model, AD is considered as
      a segmental progeria caused by shortening of anomalous chronomeres that are
      partially deleted in early development. It is proposed that a calorie-restricted
      diet retards chronomere shortening due to a local deficit of growth hormone in
      the surroundings of hypothalamic cells, thus slowing the lifelong clock and
      delaying aging. Calorie restriction increases lifespan by preserving
      mitochondrial and other organismal functions owing to the decreased chronomere
      shortening.

PMID- 17522450
TI  - A multi-method study evaluating computing-related risk factors among college
      students.
AB  - PURPOSE: To characterize undergraduate computer use using different data
      collection methods, emphasizing computing-related postures, use patterns and
      upper extremity musculoskeletal symptoms. SUBJECTS AND METHODS: In Spring, 2004,
      undergraduate students from a single dormitory at a private university agreed to
      complete a College Computing & Health Survey. For three separate data collection
      periods each lasting a week, we observed postures during computer once per period
      and continuously measured computer input device usage. During these three
      periods, students self-reported computer usage and symptoms 3-5 times daily.
      RESULTS: Thirty students participated and all completed the study. Eighty-six
      percent reported ever experiencing symptoms after computer work. There were no
      time-related trends across data collection periods for posture, symptoms, and
      computing activities and patterns. Typed work and communicating (when compared
      with playing games) were usually the predominant computing activities throughout
      the semester. There was significantly greater self-reported computer use than
      that directly measured (p<0.05). CONCLUSION: This is the first study that
      utilized several methods of exposure assessment to describe computing postures,
      use patterns and upper extremity musculoskeletal symptoms among a college student
      cohort. Epidemiological studies need to explore time-related changes such as time
      of day, weekday, and days into the semester to further understand symptoms,
      posture, and computer use changes.

PMID- 17522451
TI  - Reliability of the JobFit System Pre-Employment Functional Assessment Tool.
AB  - Functional capacity testing in the pre-employment or post-offer phase of
      recruitment is increasing in popularity as a preventative tool for controlling
      sprains and strains in the workplace. The purpose of this study is to determine
      the reliability of the JobFit System Pre-Employment Functional Assessment (PEFA)
      as a whole, or in parts, as a precursor for a validity study investigating the
      relationship between PEFA results and workplace injury rates and severity. A
      group of 28 healthy male coal mine employees were videotaped whilst they
      participated in a generic JobFit System Pre-Employment Functional Assessment
      (PEFA) including tests of aerobic physical fitness, balance, postural tolerances
      and material handling tolerances. Twenty participants performed a second trial.
      The test component scores and overall PEFA scores were compared between trials
      (test-retest, intra-rater) and assessors (inter-rater) to determine their
      reliability expressed in terms of ICC. Using an ICC score of > 0.75 as good and >
      0.90 as excellent, in conjunction with percentage agreement a good to excellent
      reliability rating was allocated to the overall PEFA score, floor to bench lift,
      bench to overhead lift, bilateral carry and climbing. A moderate to good rating
      was recorded for bench to shoulder lifts, reaching forward, reaching overhead and
      stooping. A poor to moderate rating was recorded for squatting, balance and
      fitness tests. Test-retest scores were typically lower than intra-tester and
      inter-tester scores. ICC scores should be interpreted with consideration of their
      limitations and in conjunction with the actual test results.

PMID- 17522452
TI  - The effect of ergonomic intervention on neck/shoulder and low back pain.
AB  - The aim of this study was to examine the effect of two types of ergonomic
      intervention on pain and pain-related disability in the neck/shoulder and low
      back regions. A cohort of 492 subjects of various occupations with non-specific
      neck/shoulder or low back pain was followed over a five to six year period. The
      study subjects were classified into four intervention groups: no ergonomic
      intervention, educational worksite intervention, workplace intervention, and
      combined workplace and educational worksite intervention. The group with no
      ergonomic intervention was used as the reference group. The changes in pain
      intensity and pain-related disability from baseline to follow-up in each of the
      three groups with intervention were compared to the changes in the reference
      group. During the follow-up, 39% of the subjects had received ergonomic
      intervention. The average change in pain intensity and pain-related disability
      was smaller in the educational worksite intervention group than in the reference
      group. The average reduction of pain intensity and pain-related disability did
      not differ between the two other intervention groups and the reference group.
      Thus, for subjects still at work, ergonomic intervention seemed to be ineffective
      for reducing neck/shoulder and low back pain and pain-related disability.

PMID- 17522453
TI  - Work in unemployment - occupied or preoccupied? A review.
AB  - This review explores the literature on the concept of work in unemployment and
      its relationship to health. A range of literature about the activities of
      unemployed people is reviewed and discussed with reference to three questions:
      What do unemployed people do?, What activities are associated with the health of
      unemployed people? and Do unemployed people work? From the literature, two groups
      of unemployed people are described: those who are characterised by active
      patterns of activity and those characterised by passive patterns. It is argued
      that the active group is psychologically healthier than the passive group.
      Concepts of work in both groups of unemployed individuals are presented, arguing
      that the active group seeks to replace employment with other work activities and
      that the passive group are engaged in work also, but that this presents as fret
      and preoccupation about their situation. These concepts of work are presented in
      the context of three major theoretical models of the personal impact of
      unemployment. Finally, implications for practice and directions for future
      research are suggested.

PMID- 17522454
TI  - Continuing to work after the onset of rheumatoid arthritis.
AB  - The aim of this qualitative study was to explore and describe what have made it
      possible for a group of people with rheumatoid arthritis to remain in work. There
      were ten participants, six women and four men, aged from 32 to 59. They were
      working either full time or part-time, at the time the study was conducted. Data
      was gathered using focus group interviews. The transcribed interviews were
      analysed in accordance with the constant comparative method. The result showed
      that the assets the individuals possessed and the character of the environment in
      which they worked were important reasons why they were able to remain in
      employment. Four main categories were identified: the constructive value of work,
      the characteristics of work, physical health and well-being and the understanding
      and support of colleagues. The findings support a client-centred occupational
      therapy and rehabilitation, where the experiences of the person provide the
      reason for the intervention.

PMID- 17522455
TI  - Work resumption after vocational rehabilitation: a follow-up two years after
      completed rehabilitation.
AB  - A short-term evaluation of vocational rehabilitation (VR) may give conclusions
      not automatically applicable over a longer term. The present study follows up
      alterations in work resumption or in social insurance benefits from the time of
      completed VR and during the following two years. AIM: The primary objective was
      to evaluate work resumption among previous sick-leavers granted vocational
      rehabilitation. The aim of the follow-up was to assess the stability of the
      outcome of VR over time and to analyse factors of importance for clients that
      remained at work. METHOD: A register investigation was based on 815 cases where
      the clients had taken part in vocational rehabilitation and were served by one of
      six local social insurance offices of a Swedish county. RESULTS: Of the clients
      studied, 52.4% had attained full working capacity The proportion had decreased to
      37.4% two years later. One factor that differed between those who resumed work
      and those who returned to sick leave was the duration of the previous sick-leave
      period. Those who returned to work had had shorter sick leave, had jobs to return
      to and had received job training as a vocational rehabilitation measure.
      CONCLUSIONS: The clients with the best chances of being in work two years after
      completed vocational rehabilitation were those with short sickness absence, who
      had been selected for job training as a vocational rehabilitation, were aged 16
      29 years and were employed in industry.

PMID- 17522456
TI  - Contribution of mental workload to job stress in industrial workers.
AB  - This study's central objective is to determine how several individual,
      organizational and ergonomic factors influence the relationship between job
      stress and mental workload for workers in an electronics company. A cross
      sectional study was made as a test of hypotheses regarding that relationship. The
      sample is composed of 95 workers, of both sexes, from the electronics industry in
      the metropolitan zone of Guadalajara, Jalisco, Mexico. Ergonomic conditions were
      evaluated with the Ergonomic Evaluation List, stress was evaluated by
      administering the SWS-Survey to groups of subjects, and mental workload was
      evaluated with the NASA-TLX Workload Index. Using Cochran's and Mantel-Haenzsel
      statistics, the odds ratio for each of the independent variables was {e}stimated
      as a risk factor for job stress, and analysis was later conducted by means of
      logistic regression for those risks found to be significant. Of the 95 worker
      participants, 26.3% presented a high level of job stress and 17.9% of the workers
      were found to present high levels of mental workload. The results show that
      working hours, mental demand, temporal demand, and frustration when faced with a
      given task may be considered risk factors for job stress.

PMID- 17522457
TI  - Physical, social and emotional function after work accidents: a medicolegal
      perspective.
AB  - The aim of this study was to analyse social and functional consequences of work
      accidents in a group of workers' compensation claimants who had been referred
      from the National Insurance Administration for a medicolegal assessment. The
      injured workers were evaluated on average 3 years after their accidents. Their
      medical records were analysed, and each injury was scored according to the
      Abbreviated Injury Scale (AIS). Participants completed the Short Form
      Questionnaire (SF-36). Factors relating to outcome on SF-36 were analysed using
      univariate and multivariate methods. 191 claimants returned the SF-36 (62%), 83%
      of the respondents had an AIS score of less than two, 33% reported working full
      time. Compared to population-based norms, the respondents reported significantly
      reduced health on all eight scales of SF-36. Better health and function was
      mainly associated with a higher level of education and more serious injuries. The
      extent of social support in the workplace after the accident was only partly
      related to outcome. The importance of psychosocial factors when making injury
      assessments in a medicolegal setting is highlighted.

PMID- 17522458
TI  - Hard stories in the workplace.
AB  - Relationships between family caregivers and professional health care providers
      typically begin during an intensely painful and stressful time. This article
      examines the literature on professional attitude and response to suffering with
      particular emphasis on how exposure to hard stories affects the development and
      quality of alliances with family caregivers. First person accounts from a
      qualitative, phenomenological study conducted with mothers of children with
      acquired physical disabilities are used to illustrate the perspectives of
      caregivers and the qualities they identify as contributing to competent,
      meaningful, and mutual relationships that allow for bearing witness to hard
      stories.

PMID- 17522459
TI  - Work organization and its effects on the health of Chinese workers with English
      as a second language: a qualitative approach.
AB  - Work organization consists of three contexts: (a) the external context/factors,
      (b) the organizational context/practices, and, (c) the work context/process. The
      investigation of work organization may lead to more effective prevention and
      intervention for work-related injury and illness. Studies have suggested that
      workers with limited English proficiency may be more prone to work-related injury
      and illness. The purposes of this qualitative phenomenological study were to gain
      a better understanding of the meaning of work organization to Chinese workers
      with English as a second language (ESL) and to explore their lived experiences on
      how work organization affects their health. Ten in-depth face to face interviews
      were conducted with Chinese ESL workers (5 males and 5 females; ages ranged from
      22 to 41 years) who were employed in English-speaking workplaces in the Greater
      Toronto Area, Ontario, Canada. Interviews were translated and transcribed before
      importing them into NUD*IST, a qualitative data management software program. The
      transcripts were then coded, and categories were developed based on the codes.
      Subsequently, eight themes were identified from the categories. Work organization
      was perceived by Chinese ESL workers to be at an impersonal and distant level.
      Workers also identified work organization related issues (i.e., employers'
      priority, communication, work culture, job autonomy, recognition, and individual
      characteristics) as factors affecting their health at workplaces. However, these
      workers commonly expressed resignation towards their own health. Workplaces,
      especially those with Chinese ESL workers, need to place greater emphasis on
      implementing effective health and safety approaches to maximize the health of
      these workers.

PMID- 17522460
TI  - Multiple chemical sensitivity and workplace discrimination: the national EEOC ADA
      research project.
AB  - Information from the Integrated Mission System of the United States Equal
      Employment Opportunity Commission (EEOC) was used to investigate the employment
      discrimination experiences of Americans with multiple chemical sensitivity (MCS)
      in comparison to Americans in a general disability group with allergies, asthma,
      HIV, gastrointestinal impairment, cumulative trauma disorder and tuberculosis.
      Specifically, the researchers examined demographic characteristics of the
      charging parties; the industry designation, location, and size of employers
      against whom allegations were filed; the nature of discrimination (i.e., type of
      adverse action) alleged to occur; and the legal outcomes or resolutions of these
      allegations. Findings indicate that persons with MCS were, on average, older than
      the comparison group and comparatively overrepresented by Caucasians and women.
      People with MCS were proportionally more likely than the comparison group to
      allege discrimination related to reasonable accommodations. People with MCS were
      proportionally more likely than the comparison group to file allegations against
      employers in the manufacturing and public administration industries, employers
      with 201-500 workers, and employers in the Western Census region. People with MCS
      were proportionally more likely than the comparison group to receive non-merit
      resolutions as a result of the EEOC's Americans with Disabilities Act Title I
      investigatory process. Implications for policy and advocacy are addressed.

PMID- 17522461
TI  - A new technique to achieve sufficient mesorectal excision in upper rectal cancer.
AB  - BACKGROUND: Appropriate partial mesorectal excision (PME) is extremely important
      for prevention of local recurrence even in upper rectal cancer. However, it is
      not always easy to conduct PME in the narrow pelvic cavity. We devised a new
      surgical technique that involves a rectal transection followed by PME. METHODS:
      After rectal mobilization in the layer targeted for total mesorectal excision,
      only the rectal wall was bluntly dissected at an appropriate distance from the
      tumor. Initial transection of the rectum allows drawing the rectum toward the
      anal side so that the mesorectum can be confirmed with a good visual field.
      Excision of the mesorectum was easy, and it could be resected in a short time.
      RESULTS: This technique was conducted on seven patients with upper rectal cancer
      and on four patients with rectosigmoid cancer. Separation of the rectal wall was
      comparatively easy, and we had no incidence of wall injury. The average distance
      from the rectal stump to the distal mesorectum in the freshly resected specimen
      was 15 mm, indicating satisfactory PME. CONCLUSIONS: This easily performed method
      is a promising procedure for achieving sufficient PME in upper rectal cancer.

PMID- 17522462
TI  - An unusual complication of a usually 'innocent' parasitic worm.

PMID- 17522463
TI  - An unusual small bowel perforation by a foreign body.

PMID- 17522464
TI  - Single-centre results of treatment of retroperitoneal and mesenteric cystic
      lymphangiomas.
AB  - BACKGROUND: Intra-abdominal cystic lymphangiomas are rare and usually present as
      benign large cystic masses. The treatment of choice of mesenteric and
      retroperitoneal cystic lymphangiomas is surgical resection. METHODS: Seventeen
      adults, 11 male and 6 female, with a median age of 39 years were investigated.
      Presentation, treatment, and outcomes of the mesenteric and retroperitoneal
      cystic lymphangiomas were analyzed. RESULTS: The most common symptom was
      abdominal pain. The median tumour size was 12.0 cm in diameter. Patients with
      retroperitoneal lymphangiomas were younger (p=0.043). However, 4 out of 8
      patients with the mesenteric type required bowel resection (p=0.064). Magnetic
      resonance imaging allowed a good differentiation of cystic and septal structures.
      No postoperative complications occurred, but patients with mesenteric types had
      longer postoperative stays (7.0 vs. 13.5 days; p<0.001). The long-term outcome of
      both groups was satisfactory. CONCLUSIONS: The surgical results were good with
      symptom relief. Bowel resection was common in mesenteric cystic lymphangiomas.
      Because of its higher resolution, magnetic resonance imaging is suggested.

PMID- 17522465
TI  - A prospective study of acute admissions in a surgical unit due to diverticular
      disease.
AB  - INTRODUCTION: Considerable controversy exists in the surgical literature on the
      most appropriate treatment modality for patients with recurrent diverticular
      disease. We aim to assess the clinical outcome of acute surgical admissions with
      diverticular disease, and in particular patients with recurrent admissions.
      METHODS: 100 consecutive emergency admissions with suspected diverticular disease
      were prospectively recruited from November 1, 2002 to May 31, 2004. RESULTS: The
      majority of the patients were female (64%) and the median age was 74 (45-97)
      years. The follow-up period was up to 30 months. Four patients with tumour and
      polyps as definitive diagnosis were excluded from further analysis. Fifty-four
      patients had a known history of diverticular disease with a median duration of 4
      (range 1-40) years; 44 of them had 1-7 previous emergency admissions (median 2).
      Acute diverticulitis (42%) and acute rectal bleeding (23%) were the commonest
      presentations. Patients with complicated diverticulitis requiring an emergency
      operation had a median C-reactive protein of 281 mg/l compared to 58 mg/l in the
      conservatively treated patients with acute diverticulitis (Mann-Whitney U test, Z
      -3.943, p<0.001). Nine of 14 patients operated had at least two previous
      admissions with complications of diverticular disease. Emergency operative
      treatment was associated with prolonged hospital stay (21 vs. 5 days; Mann
      Whitney U test, Z -4.367, p<0.001), increased morbidity and postoperative
      mortality. CONCLUSIONS: Symptomatic diverticular disease is associated with
      recurrent emergency admissions. The majority of patients who required emergency
      laparotomy had previous recurrent emergency admissions, which was associated with
      increased morbidity and prolonged hospital stay.

PMID- 17522466
TI  - Donor complications including the report of one death in right-lobe living-donor
      liver transplantation.
AB  - BACKGROUND/AIMS: Our objective is to assess donor complications in all right
      hepatic lobe living-donor liver transplantation (LDLT) at our center. METHODS: Of
      a total of 352 liver transplantations performed, 60 were right-lobe LDLT. Most
      donors (88.3%) were related to the recipients. RESULTS: Mean hospital stay was
      5.4+/-0.6 days. No complications occurred due to preoperative evaluation. Most
      donors received one or two units of autologous blood transfusion. Only 5 (8.3%)
      needed nonautologous blood transfusion. Most complications were minor and treated
      conservatively. Bile leaks from the cut surface of the liver occurred in 5 donors
      (8.3%). Two patients had potentially fatal complications: perforated duodenal
      ulcer and portal vein thrombosis (PVT). The donor with perforated ulcer developed
      septicemia and multiple organ failure. He was discharged from the hospital with
      hemiparesis due to cerebral ischemia. The patient with PVT remained asymptomatic
      and the portal vein was recanalized by the 3rd postoperative month. One donor
      died in the immediate postoperative period of cardiac arrest due to cardiac
      arrhythmia. CONCLUSION: Right hepatectomy for LDLT may be associated with
      significant morbidity, including death and it should be performed only by
      surgeons with great experience.

PMID- 17522467
TI  - Botulinum toxin A injection in ISDN ointment-resistant chronic anal fissures.
AB  - BACKGROUND: In the treatment of chronic anal fissures (CAFs), surgical
      sphincterotomy is more commonly being replaced by chemical sphincterotomy. After
      the good results of our pilot study including 32 patients, we now describe the
      effect of botulinum toxin A (BT-A) in a consecutive series of 100 patients with
      isosorbide dinitrate (ISDN) ointment-resistant CAFs. METHODS: From October 2002
      until August 2005, 100 patients (52 males, 48 females) with a median age of 45
      (20-79) years were treated with an injection of 40-100 IU BT-A (Dysport, Ipsen,
      The Netherlands) in the internal anal sphincter. RESULTS: After a median follow
      up of 10 (4-38) months, 77 of the 100 CAFs (77%) were cured. 20 patients were
      given a second injection, 1 a third and 1 a fourth injection. In 11 patients a
      fissure recurred (14%). In 1 patient (1%) there was temporary incontinence due to
      flatus. CONCLUSION: With an early response rate of 77% and an overall success
      rate of 66%, BT-A injections appear to be effective in patients with ISDN
      ointment-resistant CAFs if initial non-responders are retreated. These results
      are in concordance with the results of our pilot study. It is a simple technique
      with little or no side effects, that does not compromise future treatments. Its
      place in the first-line treatment of CAFs should be investigated further.

PMID- 17522468
TI  - Acid corrosive injury in patients with a history of partial gastrectomy: outcome
      analysis.
AB  - BACKGROUND: Our purpose was to delineate the characteristics and outcome of acid
      corrosive injury in patients with a history of gastric resection. MATERIAL AND
      METHODS: A total of 359 patients with a history of acid-corrosive injury were
      retrospectively reviewed. They were grouped based on past history with group 1
      consisting of 8 patients with a history of gastric surgery (6 hemigastrectomies
      with Billroth II gastrojejunostomy, 2 partial gastrectomies with Billroth I
      gastroduodenostomy) and group 2 consisting of 351 patients without a history of
      previous gastric surgery. Clinical data, operative findings, treatment modalities
      and prognoses were compared. RESULTS: Group 1 patients required significantly
      more emergency surgical interventions (p=0.016) and more frequent resection of
      alimentary necrosis (p=0.007). In the operative findings of those undergoing
      emergency laparotomy, group 1 had a slightly higher incidence of total gastric
      necrosis with or without perforation (p=0.388), and a higher incidence of jejunal
      resection (p=0.001). However, group 1 patients had a relatively lower operative
      mortality rate compared to group 2 patients (p=0.640). CONCLUSION: Acid-injured
      patients with a history of previous gastric surgery tended to have a higher
      incidence of mandatory emergency surgical exploration and resection of the
      alimentary tract. With early and prompt management, a good survival rate can
      still be anticipated.

PMID- 17522469
TI  - Role of mesohepatectomy with or without transcatheter arterial chemoembolization
      for large centrally located hepatocellular carcinoma.
AB  - BACKGROUND: The role of preoperative transcatheter arterial chemoembolization
      (TACE) for resectable hepatocellular carcinoma (HCC) was controversial. METHODS:
      246 patients with large centrally located HCC underwent mesohepatectomy (MH) and
      were divided into two groups: group A, 89 patients with preoperative TACE; group
      B, 157 patients without preoperative TACE. The aim was to evaluate the influence
      of preoperative TACE on postoperative complications and long-term results of
      patients with large centrally located HCC. RESULTS: In the 89 patients of the
      TACE-MH group, a total of 123 (mean 1.4 per patient) preoperative TACEs were
      performed. The differences in postoperative complications (34.8 vs. 24.2%;
      p=0.075) and overall hospital mortality (3.4 vs. 0.6%; p=0.103) between the two
      groups were not significant. The postoperative recurrence rate in the remnant
      liver was higher in the MH group than in the TACE-MH group (79.6 vs. 73.0%),
      while the extrahepatic metastasis rate in the TACE-MH group was higher than that
      in the MH group (11.1 vs. 7.0%). Overall 1-, 3-, and 5-year survival rates were
      87.1, 62.9, and 46.2%, respectively, for the TACE-MH group, and 82.2, 54.4, and
      31.7%, respectively, for the MH group (p=0.001); 1-, 3-, and 5-year disease-free
      survival rates were 75.0, 46.2, and 31.8%, respectively, for the TACE-MH group,
      and 69.6, 38.0, and 16.5%, respectively, for the MH group (p=0.002). CONCLUSIONS:
      Long-term outcomes of patients with preoperative TACE were improved and the
      pattern of the recurrences after surgery was altered. The patients with large
      centrally located HCC could benefit more from this neoadjuvant treatment,
      although there was some influence of preoperative TACE on postoperative
      complications.

PMID- 17522470
TI  - Tonometer pHi monitoring of free jejunal grafts following
      pharyngolaryngoesophagectomy for hypopharyngeal or cervical esophageal cancer.
AB  - BACKGROUND/AIMS: Graft failure is a critical complication associated with
      vascular occlusion in esophageal reconstruction with a free jejunal graft
      following pharyngolaryngoesophagectomy. In this study, we evaluated the
      usefulness of intramucosal pH (pHi) measurement using a tonometer to assess the
      graft viability. METHODS: Two consecutive studies, the early phase study and the
      late phase study, were performed. Nineteen patients who underwent free jejunal
      transfer were enrolled in the early phase study before 1999 to determine the
      critical pHi value. In the late phase study after 2000 (n=16), anticoagulant
      treatment to prevent graft necrosis was performed in the patients having a pHi
      value under the critical level. RESULTS: In the early phase study, vascular
      obstruction was not seen in 16 patients with pHi>7.10. Of 3 patients with
      pHi<7.10, 2 underwent regrafting because of jejunal graft necrosis by vascular
      obstruction. In the late phase study, reoperation was not required in 3 of 4
      patients with pHi<7.10. Intraoperative vascular occlusion was found in 1 patient
      with a decline in pHi value and anticoagulant treatment was effective in 2
      others. CONCLUSION: The pHi measurement using a tonometer is useful for finding
      vascular problems in free jejunal grafts.

PMID- 17522471
TI  - A practical method of measuring glomerular filtration rate by iohexol clearance
      using dried capillary blood spots.
AB  - BACKGROUND: Exogenous tracer-based methods of measuring glomerular filtration
      rate (GFR) are difficult to perform, whilst creatinine-based estimation formulae
      are inaccurate. METHODS: We assessed a new technique of measuring iohexol
      clearance using timed dried capillary blood spots. A reference GFR was measured
      in 81 subjects (GFR 15-124 ml/min/1.73 m(2)) by iohexol clearance using three
      venous samples (2, 3 and 4 h after an intravenous bolus). GFR was estimated by
      six test methods; iohexol clearance using (i) 3 blood spots (2, 3, 4 h); (ii) 2
      blood spots (2, 4 h) and (iii) 1 blood spot (4 h); (iv) the Modification of Diet
      in Renal Disease (MDRD) formula; (v) the Cockcroft-Gault formula, and (vi) a
      formula estimating GFR from serum cystatin C concentration. For each test method
      the bias and precision were calculated as the mean and standard deviation (SD) of
      the 'GFR differences' (test method GFR - reference GFR). RESULTS: The limits of
      agreement (bias +/-1.96 x SD; in ml/min/1.73 m(2)) were: (i) 1.1 +/- 15.1 for 3
      spot iohexol clearance; (ii) 0.6 +/- 14.9 for 2-spot iohexol clearance; (iii) 4.5
      +/- 21.2 for 1-spot iohexol clearance; (iv) -15.7 +/- 33.3 for the MDRD formula;
      (v) -9.6 +/- 32.9 for the Cockcroft-Gault formula, and (vi) -12.1 +/- 31.7 for
      the Cystatin C formula. The accuracy of all six test methods was similar among
      individuals with GFR <60 ml/min/ 1.73 m(2); however, in individuals with GFR > or
      =60 ml/min/ 1.73 m(2), the MDRD, Cockcroft-Gault and Cystatin C formulae were all
      imprecise and systematically underestimated GFR. CONCLUSIONS: Blood spot iohexol
      clearance provides a potentially practical method of estimating GFR accurately in
      large-scale epidemiological studies especially among individuals without
      established chronic kidney disease.

PMID- 17522472
TI  - Relationship between the degree of malnutrition and echocardiographic parameters
      in hemodialysis patients.
AB  - BACKGROUND: The aim of this study is to investigate the relationship between the
      degree of malnutrition and inadequate volume control evidenced by
      echocardiography. METHODS: In this study 72 chronic hemodialysis patients were
      investigated in a cross-sectional manner. The malnutrition score was calculated
      using Subjective Global Assessment. M-mode echocardiography was performed in all
      patients. RESULTS: The highest malnutrition score (23.2 +/- 1.5 points) and
      lowest vena cava inferior collapse index (35 +/- 2%) were observed in the
      eccentric left ventricular hypertrophy group. The malnutrition index was found to
      be in positive relationship with the left atrium diameter and index, left
      ventricular mass and index, and left ventricular end-diastolic diameter. On the
      other hand, a negative correlation was detected with the vena cava inferior
      collapse index. When all parameters that were found to be related to malnutrition
      were assessed by multivariate analyses, a statistically significant relation was
      found between the left ventricular end-diastolic diameter and the malnutrition
      index. CONCLUSION: The results of our study show that the progressive worsening
      of the nutritional status follows a parallel course along with the deterioration
      in the echocardiographic parameters concerning hypervolemia. This in turn
      suggests that increasing degrees of malnutrition are associated with more
      profound derangements in the volume status. Volume excess might be a mechanism
      explaining the increased mortality and morbidity caused by malnutrition in
      hemodialysis patients. Owing to its cross-sectional design, this study cannot
      provide unequivocal evidence regarding the cause and effect relationship between
      volume overload and malnutrition in hemodialysis patients.

PMID- 17522473
TI  - Referral to nephrologists for chronic kidney disease care: is non-diabetic kidney
      disease ignored?
AB  - BACKGROUND: Late referral to nephrologists is common and associated with
      increased morbidity and mortality. We aimed to analyze the prevalence rates,
      predictors and consequences of late referral to nephrologists by primary care
      physicians for chronic kidney disease (CKD) care. METHODS: A retrospective
      analysis of 204 patients started on dialysis for CKD in two community hospitals
      between March 2003 and March 2005 was conducted. Relevant clinical and laboratory
      data were obtained from the patient records of the nephrology clinics and
      dialysis units. Patients referred in CKD stage 5 (estimated glomerular filtration
      rate <15 ml/min) were defined as late referral and patients in CKD stage 1-4
      (estimated glomerular filtration rate >15 ml/min) as early referral. RESULTS:
      Forty-five (22%) of the 204 patients were referred late. In the multivariate
      analysis, non-diabetic kidney disease (odds ratio = 2.46, p = 0.02) and Charlson
      comorbidity index (odds ratio = 1.17, p = 0.009) were significantly associated
      with late referral. The late referral group had lower hematocrit and serum
      calcium levels, and higher serum phosphorus and parathyroid hormone levels than
      the early referral group (p < or =0.05) at the time of referral. Late referral
      resulted in less permanent vascular access for initiation of dialysis (p = 0.03).
      Even though there was twice the number of deaths in the late referral group in 1
      year (18 vs. 9%), this was not statistically significant (p = 0.07). CONCLUSION:
      Referring physicians should pay special attention to patients with non-diabetic
      kidney disease and patients with multiple comorbidities since delayed referral to
      nephrologists may result in poorer patient-related outcomes. Larger and long-term
      prospective studies analyzing the long-term consequences of late referral to
      nephrologists are needed.

PMID- 17522474
TI  - A critical appraisal of the radiological evaluation of nephrocalcinosis.
AB  - BACKGROUND/AIM: The level of agreement concerning the diagnosis of
      nephrocalcinosis (NC) based on ultrasonography (US), computed tomography (CT) or
      kidney/ureter/bladder (KUB) X-ray was assessed. METHODS: Sequences of KUB+US+CT
      from 62 patients, 48 with at least one exam suggesting NC and 14 with
      pelvicalyceal calcifications (nephrolithiasis) were reviewed twice by 3
      radiologists (firstly randomized and secondly presenting KUB+US+CT of each
      patient together). RESULTS: The intraobserver concordance varied from 76 to 90%
      for KUB, 77 to 85% for US and 82 to 89% for CT. There was a significant change in
      diagnosis between the 1st and 2nd reviews for observer 1 in KUB and CT, for
      observer 2 in US, but not for observer 3. Evaluating patients' exams together did
      not provide a better agreement. The highest sensitivity and specificity (92 and
      89%, respectively) were only attained when 2 exams suggested NC diagnosis, being
      CT one of them. These enabled us to suggest that 33 out of 48 (62.5%) patients
      had NC (evidenced in US+CT+KUB (81.8%), US+CT (12.1%) or KUB+CT (6.1%).
      CONCLUSION: The low level of concordance renders the radiological diagnosis of NC
      difficult. Nephrocalcinosis should be confirmed by CT combined with either US or
      KUB.

PMID- 17522475
TI  - Nandrolone decanoate as anabolic therapy in chronic kidney disease: a randomized
      phase II dose-finding study.
AB  - BACKGROUND/AIMS: In patients with chronic kidney disease (CKD) receiving adequate
      erythropoietin therapy, the ideal dose of nandrolone decanoate (ND) to enhance
      muscle mass is not known. METHODS: In this phase II dose-finding study, 54
      patients with CKD stage 5 were randomized to either low, medium or high doses of
      ND (50, 100 or 200 mg/week for 24 weeks, respectively, in males; doses halved in
      females), while 7 patients acted as non-randomized controls. The primary outcome
      measure was appendicular lean mass (ALM) by dual-energy X-ray absorptiometry.
      Fluid overload (hydration of the fat-free mass) and indicators of physical
      functioning were secondary measures. Harms were also recorded. Data were analysed
      using Quade's (1967) non-parametric analysis of covariance. RESULTS: ND increased
      ALM in a dose-responsive manner (change scores = 0.3 +/- 0.3 vs. 0.8 +/- 0.3 vs.
      1.5 +/- 0.5 vs. 2.1 +/- 0.4 kg, control vs. low vs. medium vs. high dose groups,
      respectively, p < 0.001) with no increases in fluid overload but no consistent
      effect on physical functioning. The highest dose of ND (100 mg/week) was
      intolerable in females because of virilizing effects. CONCLUSION: If goals of
      future studies are to improve body composition, dosing of ND up to 200 mg/week in
      males and 50 mg/week in females should be investigated. However, to realize
      improvements in physical functioning, future phase III trials of ND may require
      additional interventions such as exercise training.

PMID- 17522476
TI  - Quality of life of patients with nephrolithiasis and recurrent painful renal
      colic.
AB  - BACKGROUND: Quality of life (QoL) has not been a priority goal for patients with
      recurrent painful colic of renal lithiasis. AIM: To evaluate QoL in patients with
      recurrent painful symptoms due to renal colic. METHODS: In this case-control
      study, 194 subjects (97 cases/97 controls) were matched according to age and
      gender. Cases were patients at an outpatient clinic with a confirmed diagnosis of
      nephrolithiasis with recurrent painful renal colic. The control group consisted
      of patients seen at an ophthalmology outpatient clinic for refraction symptoms.
      MAIN OUTCOME MEASURES: QoL was measured using the SF-36. RESULTS: Average SF-36
      dimension scores for cases and controls, respectively, were: physical function
      70/95, role-emotional function 33.3/100, role limitations due to physical
      problems 25/100, bodily pain 41/84, general health status 52/82, vitality 45/80,
      social function 62.5/100 and mental health 52/84. All values were statistically
      different (p < 0.001). Using multiple linear regression, there was a
      statistically significant QoL drop in subjects with lithiasis. Low social and
      economic levels were associated with the following SF-36 domains: physical
      function, general health status, vitality and mental health. The influence of the
      diagnosis on role-physical and role-emotional domains. Analysis of the physical
      and mental components of the SF-36 Scale showed significantly lower averages
      between cases and controls: PCS (p < 0.001) and MCS (p < 0.001). CONCLUSION: The
      QoL of patients with painful recurrent symptoms due to renal colic was
      substantially impaired.

PMID- 17522477
TI  - Association of metabolic syndrome with microalbuminuria in non-hypertensive type
      2 diabetic patients.
AB  - BACKGROUND: Several studies have shown that metabolic syndrome contributed to the
      development of incident chronic kidney disease in the general population. We
      evaluated the cross-sectional association between metabolic syndrome and
      microalbuminuria in patients with type 2 diabetes. We excluded patients with
      hypertension to distinguish the effects of metabolic syndrome from those of
      hypertension. METHODS: A total of 642 non-hypertensive patients with type 2
      diabetes were recruited. Metabolic syndrome was assessed according to the NCEP
      Guidelines and Asian-Pacific criteria for abdominal obesity. RESULTS: Among all
      patients, 37.2% were diagnosed as having metabolic syndrome, and these patients
      had a higher prevalence of microalbuminuria than those without metabolic syndrome
      (19.7 vs. 13.6%, p = 0.044). There was a graded association between metabolic
      score and the prevalence of microalbuminuria (p = 0.006 for trend). After
      adjustment for sex, age, smoking status, C-reactive protein, and HbA(1c),
      patients with metabolic syndrome had increased odds of 1.58 (95% CI 1.01-2.47)
      for microalbuminuria. An increment in metabolic score was found to increase the
      risk of microalbuminuria by 1.34-fold (95% CI 1.07-1.66, p = 0.008). CONCLUSION:
      This study demonstrated that metabolic syndrome was associated with an increased
      risk of microalbuminuria in non-hypertensive patients with type 2 diabetes.

PMID- 17522478
TI  - Cone photoreceptor diversity in the retinas of fruit bats (megachiroptera).
AB  - Older studies have claimed that bats including the Megachiroptera (fruit bats or
      flying foxes) have pure-rod retinas and possess no cone photoreceptors. We have
      determined the presence and the population densities of spectral cone types in
      six megachiropteran species belonging to four genera: Pteropus rufus, P. niger,
      P. rodricensis, Rousettus madagascariensis, Eidolon dupreanum, and Epomophorus
      gambianus. Spectral cone types and rods were assessed immunocytochemically with
      opsin-specific antibodies. All six species have rod-dominated retinas but possess
      significant cone populations. The high rod densities (range 350,000
      800,000/mm(2), depending on species and retinal location) provide good scotopic
      sensitivity in these predominantly nocturnal animals. With the cones (density
      range 1,300-11,000/mm(2), corresponding to 0.25-0.6% of the photoreceptors,
      depending on species and retinal location) the retinas also possess the
      prerequisite for vision at photopic light levels. The three Pteropus species have
      two spectral cone types, a majority of middle-to-long-wave sensitive (L-) cones,
      and a minority of short-wave sensitive (S-) cones, indicating the potential for
      dichromatic color vision. This conforms to the pattern found in most mammals. In
      contrast, Rousettus, Eidolon and Epomophorus have L-cones but completely lack S
      cones, indicating cone monochromacy and color blindness. The discussion relates
      these findings to the visual behavior of fruit bats.

PMID- 17522479
TI  - The surgeon's role and responsibility in facial tissue allograft transplantation.
AB  - Facial composite tissue allograft (CTA) transplantation represents a novel
      frontier in the reconstruction of the human form. The face plays a central role
      in human interactions, with significant social ramifications resulting from
      facial disfigurement. The surgeon performing facial tissue transplantation bears
      additional responsibilities unique to plastic and reconstructive procedures.
      Reconstruction by facial tissue transplantation may immensely improve quality of
      life, provided the process of patient selection is conspicuous and appropriate
      and allograft rejection is prevented. However, facial CTA transplantation
      represents an elective procedure to reconstruct a non-life-threatening defect.
      Given the potential for organ failure, opportunistic infection, and malignancy
      resulting from long-term immunosuppression, the surgeon must carefully weigh the
      balance of risk to benefit for the individual patient. Pioneering surgeons
      developing this procedure must thoroughly evaluate its impact as it relates to
      clinical and social issues.

PMID- 17522480
TI  - Introduction of an easy technique for purification and injection of autogenous
      free fat parcels in correcting of facial contour deformities.
AB  - BACKGROUND: Facial contour deformities usually result from congenital
      abnormalities, trauma, and the aging process. All depressions in the face,
      including glabella wrinkles and mild retrogression of chins, fall in this
      category. Local injection of autogenous fat parcels has been introduced for
      correction of these facial deformities for almost 20 years. METHOD: Using common
      materials (gauzes and cotton sticks), a simple technique was used by us to purify
      syringe-suctioned fat parcels followed by a multilayered injection of the
      purified fat tissue into implantation sites to treat the facial contour
      deformities in 152 sites of 50 cases with successful outcomes. RESULTS: Thirty
      nine sites in 17 cases were followed up from 13 months to 37 months (average,
      22.8 months). The injected fat parcels deposited successfully and the increasing
      volume maintained well. The impact factors on the successful deposit of the
      injected fat parcels included the extent of mechanical injuries to the fat cells
      during liposuction and lipoinjection, application of the purification procedure,
      and postsurgery immobilization as well as the blood-nourishing situation of
      recipient sites. Postoperative complications included undercorrection,
      overcorrection, small fat mass, unevenness, or irregularity. CONCLUSION: The
      introduced purification and injection techniques provided a comparative simple
      and reliable method in facial recontouring treatment. The local volume could be
      increased successfully by means of controlling the influencing factors of fat
      parcel deposit.

PMID- 17522481
TI  - Facial acne and fine lines: transforming patient outcomes with plasma skin
      regeneration.
AB  - BACKGROUND: A novel device for skin rejuvenation has been developed and tested.
      The device converts a stream of nitrogen into a plasma of ionized gas, which
      ablates surface tissue in a controlled manner. METHODS: Eleven patients were
      followed up for 6 months. The results were assessed objectively using skin molds
      to measure skin irregularity, as well subjectively using patient- and doctor
      assessed parameters. RESULTS: Plasma skin regeneration was shown to reduce fine
      line wrinkles by an average of 24% at 6 months (P = 0.005, Mann-Whitney rank sum
      test) and to improve acne scarring by 23% at 6 months (P = 0.001, Mann-Whitney
      rank sum test). CONCLUSIONS: The main benefit of this system was that the
      patients had minimal erythema lasting only 1-6 days and no pigmentary changes.
      This is therefore a device with proven efficacy and limited morbidity.

PMID- 17522482
TI  - Perforator-sparing transposition flaps for lower limb defects: anatomic study and
      clinical application.
AB  - The local fasciocutaneous flap has the advantage of low donor-site morbidity when
      used for the coverage of lower limb defects. However, flap reliability remains a
      major problem with its use. The purpose of this study was to determine the
      feasibility of preserving perforators to the tip of conventional local
      fasciocutaneous flaps to improve its vascularity. The technical considerations of
      raising these flaps were examined in cadaveric specimens. Twenty-one local
      perforator-sparing transposition flaps were raised in 12 specimens. The leg was
      divided into knee/proximal-third, middle-third, and lower-third/ankle regions. We
      raised 7 flaps in each region. Success was defined as ability to transpose flaps
      to cover defects without tension on the perforators. In the knee/upper-third and
      middle-third regions of the leg, all wounds were successfully closed. However in
      the lower-third and ankle region, we were unable to close wounds in 3 of 7 cases.
      The reasons for this were the inadequate length of the perforator and the
      presence of tendons in the distal leg that interfered with perforator
      transposition. We successfully employed this flap in 6 clinical cases. This flap
      represents a technical advancement over conventional lower limb skin flaps
      because of its improved vascularity. It can safely be performed in the knee and
      upper and middle-thirds of the leg and can potentially be a valuable alternative
      to local muscle flaps for wounds in these areas.

PMID- 17522483
TI  - Self-inflicted burns.
AB  - During the last few years, a unique group of patients was recognized among the
      burn patients treated in our institution. They were all young men with small,
      isolated, lower-extremity burns that, in appearance, were not compatible with the
      claimed etiology. In an attempt to characterize these patients, we
      retrospectively screened the charts of all isolated lower extremity burn patients
      in our Plastic Surgery Department during a 2-year period, comparing the
      suspicious burns to our other patients. We found that there were 25 patients out
      of 56 that were suspected of having self-inflicted burns. All the patients in
      this group were male soldiers, with a mean age of 19.5 years. The length of
      hospitalization per percentage of burn was longer in these patients than in the
      other patients. We feel that this group of patients is a recognizable subunit
      that should be treated both by physicians and psychologists.

PMID- 17522484
TI  - Proximal interphalangeal joint fractures of the hand: treatment with an external
      dynamic traction device.
AB  - The authors present a series of 11 consecutive patients who sustained an intra
      articular fracture of the proximal interphalangeal (PIP) joint and 1 patient with
      a fracture of the interphalangeal joint of the thumb treated with a Kirschner
      wire external dynamic traction device. Range of motion and grip strength were
      measured. We used the Michigan Hand Outcome Questionnaire (MHQ) to obtain a
      subjective response to the treatment. Average range of motion of the PIP joint
      was 64 degrees and distal interphalangeal joint was 52 degrees . The average grip
      strength was 86% with a mean MHQ score of 90. Two patients had pin site
      infections treated successfully with antibiotics. All fractures had united at
      final follow up with <1-mm articular step present. Our series highlights that
      these are difficult injuries to treat and that anatomic reduction is not always
      possible. However, this technique is simple and quick to perform while allowing
      early joint mobilization. The subjective response to treatment is comparable with
      other studies using a similar device.

PMID- 17522485
TI  - Upper extremity salvage with a flow-through free flap.
AB  - In complex extremity injuries, which include composite tissue lost with
      devascularization caused by segmental vascular damage, simultaneous coverage of
      the defects with revascularizations should be required. One-stage reconstruction
      of both soft tissue coverage and vascular damage can be performed by a flow
      through-type free flap. In this series, 5 patients between 13 and 36 years of age
      with wide composite tissue defects in the cubital region and segmental defects in
      brachial arteries were operated at our clinic between 1996 and 2003. With the aim
      of reconstructing the wide tissue defects in the cubital region as well as that
      of the brachial artery, a radial arterial flow-through flap was applied. The
      radial artery of the flow-through flap was anastomosed to the proximal ends of
      the brachial and ulnar arteries in an end-to-end fashion. In 4 of the patients,
      the radial arterial flow-through flap was prepared from the distal aspect of the
      wounded forearm and in 1 patient from the contralateral forearm. In the
      postoperative period, no complications related to the anastomosis were
      encountered in the flap with all anastomoses found to be patent, and distal
      circulation was restored. The radial arterial flow-through flap is very useful in
      the clinical field of major trauma of the cubital region with brachial artery
      damage with numerous advantages that include the opportunity to work in one
      single surgical area, shorter dissection times resulting from simple and fixed
      anatomy, perfect color and tissue adaptation, and the suitability of the vessel
      caliber and length.

PMID- 17522486
TI  - Ulnar shortening osteotomy with a premounted sliding-hole plate.
AB  - BACKGROUND: Ulnar shortening osteotomy represents a common procedure for various
      ulnar-sided wrist disorders but is still associated with complications like
      malrotation, angulation, or nonunion because of incomplete closure of the
      osteotomy gap. We describe the use of a newly developed palmarly placed sliding
      hole dynamic compression plate that allows fixation of the ulna before the
      oblique osteotomy is carried out. METHODS: We performed ulnar shortening
      osteotomy on 27 consecutive patients. The indication was ulnar impaction syndrome
      in 25 patients and symptomatic ulnar plus variance secondary to malunited distal
      radial fracture in 2 patients. The mean preoperative ulnar variance was +2.1 mm
      (range, +1 mm to +8 mm). All patients were evaluated before and after surgery and
      graded with the Disability of Arm-Shoulder-Hand (DASH) scoring system. RESULTS:
      All 27 osteotomies healed uneventfully over an average of 9.2 +/- 2.1 weeks. The
      mean postoperative ulnar variance was -2.1 mm (range, -3.1 mm to 0 mm). There
      were significant improvements in DASH score, pain, and grip strength at an
      average follow-up of 8.1 months. Six patients complained of plate irritation.
      CONCLUSION: Favorable results suggest that ulnar shortening osteotomy using an
      oblique osteotomy and a premounted sliding-hole compression plate avoids
      malrotation and angulation and is associated with satisfactory outcomes. This
      device does not require an assisting device, which minimizes the surgical
      exposure of the ulna. Palmar placement of the plate seems to reduce hardware
      irritation.

PMID- 17522487
TI  - Rigid fixation of the sternum using a new coupled titanium transverse plate
      fixation system.
AB  - Restoration of sternal integrity after median sternotomy for cardiac
      interventions better ensures optimal postoperative pulmonary function and
      minimizes overall morbidity. Sternal dehiscence or nonunion mitigates against
      such a successful outcome. Under such circumstances, if enough viable and
      uninfected sternum remains, an anatomic reduction should be attempted. Rewiring
      usually proves unsuccessful, and rigid plate fixation is more rewarding. A new
      titanium sternal fixation system that permits transverse orientation of plates
      has been used in 4 patients who had sterile complete or imminent sternal
      dehiscence to allow eventual sternal union. The specific advantage of this new
      system is the presence of a releasing pin in the center of coupled plates to
      allow rapid chest reentry if required without the specific need for cumbersome
      plate removal. One patient had delayed removal of an infected plate after sternal
      union was achieved.

PMID- 17522488
TI  - Two-stage surgical treatment of severe cherubism.
AB  - Cherubism is an autosomal-dominant syndrome characterized by excessive bilateral
      maxillomandibular bony degeneration followed by fibrous tissue hyperplasia. Eight
      patients (age, 6-15 years; mean, 11 years) with severe cherubism were treated
      with a 2-stage operation by the same senior surgeon (C.M.R.-A.) over an 18-year
      period, 1987 through 2005. Severity was based on a modified Motamedi
      classification system. The diagnosis was established clinically,
      radiographically, and histologically. Postoperative follow up ranged from 2 to 18
      years (mean, 5.1 years). All patients underwent 2-stage surgical treatment. In
      the first stage, the anterior wall of the maxilla was osteotomized and removed (n
      = 5). The cherubic lesion was curetted from the maxilla and orbits. The maxilla
      was recontoured on the back table and then fixed orthotopically with wires.
      Alternatively, cortical bone windows were created, the maxillary and orbital
      lesions were curetted, and the maxilla was infractured and recontoured in situ
      with manual pressure (n = 3). Six months after the maxillary/orbital procedure,
      all patients underwent second-stage curettage and recontouring of the mandible
      using bony access windows and manual infracture. Satisfactory esthetic results
      were achieved in all patients. The patients remained clinically and
      radiographically disease-free throughout the follow-up period. The most
      profoundly affected patient sustained bilateral lower eyelid ectropion that
      resolved with full-thickness skin grafting. Although cherubism tends to abate by
      the fourth decade of life, early 2-stage surgical curettage provides a simple and
      reliable treatment that not only delivers immediate results, but also seems to
      arrest the growth of any remaining cherubic tissue.

PMID- 17522489
TI  - Novel lymphography using indocyanine green dye for near-infrared fluorescence
      labeling.
AB  - Lymphedema is known to be caused by many pathologic conditions; however, its
      diagnostic and therapeutic strategies remain to be unestablished. In this study,
      we investigated the usefulness of a novel lymphographic method based on
      fluorometric sensing using indocyanine green (ICG) dye for imaging lymphatic
      vessels using rat models. The real-time imaging system enabled visualization of
      superficial lymphatic vessels with a diameter of 0.1 mm in 33 frames/second. In
      addition, morphologic changes in lymphatic vessels in a radiation-induced
      lymphedema model were detected even at the latent stage. These results suggest
      that this imaging technique is acceptable as an evaluation method for the
      lymphatic system.

PMID- 17522490
TI  - Cryopreservation of composite tissue flaps: experimental studies in the rat.
AB  - Cryopreservation has the potential to improve availability of donor parts for
      composite tissue allotransplantation and may reduce their antigenicity. This
      study investigates whether the component tissues of composite flaps remain viable
      after cryopreservation. Forty-one epigastric flaps were harvested from Lewis
      rats. Twenty-one flaps were perfused with DMSO/trehalose, frozen by controlled
      cooling to -140 degrees C, and stored in liquid nitrogen for 2 weeks. Ten fresh
      and 10 cryopreserved/thawed flaps were examined histologically with hematoxylin &
      eosin and factor VIII staining. An epithelial viability index was calculated for
      10 fresh and 11 cryopreserved flaps using the MTT assay. In all cryopreserved
      samples, hematoxylin & eosin, and factor VIII staining revealed a well-preserved
      cellular architecture, which was indistinguishable from fresh specimens. The
      viability index for the cryopreserved samples was 10.90 +/- 2.09 compared with
      12.15 +/- 1.32 for fresh flaps (P = 0.123). Results suggest that the skin,
      adipose, and vascular endothelial cells of composite tissue flaps retain their
      viability after cryopreservation and thawing.

PMID- 17522491
TI  - Reactive oxygen species in experimental ischemic flow-through venous flaps and
      effects of antioxidants on reactive oxygen species and flap survival.
AB  - We made an experimental study on rabbit ears using an ischemic flow-through
      venous flap model to determine the changes in levels of reactive oxygen species
      (ROS) in venous flaps and effects of exogenous antioxidants on endogenous
      antioxidant superoxide dismutase (SOD) and ROS indicator malonyldialdehyde (MDA)
      levels and on flap survival. Mean SOD level significantly decreased and the MDA
      level significantly increased after the flap elevation according to basal levels
      of untreated flaps. The mean flap survival rates in the exogenous SOD or
      glutathione (GSH)-treated groups were significantly increased with respect to the
      untreated group. The SOD level was increased significantly and the MDA level was
      decreased significantly in the SOD- or GSH-treated groups relative to the control
      group after the flap elevation. These results have suggested that ROS may have an
      important role in ischemic flow-through venous flap pathogenesis and
      additionally, antioxidants could enhance the rate of flap survival.

PMID- 17522492
TI  - Crossover replantation of the foot after bilateral traumatic lower extremity
      amputation.
AB  - BACKGROUND: Bilateral traumatic amputation and limb-threatening injury of the
      lower extremities is more challenging than the unilateral amputation. Successful
      replantation of both lower extremities has been reported previously. However,
      orthotopic implantations may not be possible when amputation of both lower limbs
      with different levels of section and degrees of damage to surrounding tissues
      occurs. It was reported that the crossover replanted foot in combination with
      prosthetic limb is better than 2 artificial limbs. Hence, crossover replantation
      should be considered when anatomic replantation of both lower extremities is not
      possible as a result of bilateral total or subtotal amputation. To our knowledge,
      there are few reports about the crossover replantation of the lower extremity in
      the literature. CASE REPORT: A 30-year-old engineer being run over by the train
      had crushed the bilateral lower limbs in different anatomic levels. We decided to
      perform the crossover replantation of the right foot to the stump of the left leg
      to provide the patient with at least 1 weight-bearing sensate extremity. At the
      latest follow-up examination, 30 months after the operation, he had mild pain,
      especially in toes of the replanted foot. There was no ulceration in both the
      replanted extremity and the right amputation stump. The sole has maintained
      complete protective sensation. The patient described the functional result of the
      reimplanted leg as satisfying and better than the prosthesis that has caused much
      more problems than the replanted extremity. He had no complaint about the
      cosmetic result. He stated that he would have the crossover replantation again
      under the same condition. He was able to return to his previous job. Moreover, he
      affirmed that he is able to carry on his all social activities as he had done
      before the accident except for playing football. In conclusion, the possibility
      of the crossover replantation should be considered while evaluating the patient
      with bilateral lower limb injuries to allow the patient to stand on their own
      foot and still touch ground.

PMID- 17522493
TI  - Incidental discovery of bilateral breast cancer in a 24-year-old man presenting
      with gynecomastia.
AB  - We present a case of a 24-year-old man who was treated for gynecomastia with
      bilateral mastectomy and free nipple grafts with subsequent discovery of
      bilateral breast cancer in the submitted specimens. Surgical treatment of
      gynecomastia is becoming more popular with over 16,000 procedures of gynecomastia
      reduction performed in 2005, an increase of 17% compared with the previous year.
      This case underscores the rare but real possibility of detecting breast cancer in
      men who present with gynecomastia to plastic surgeons. We caution that male
      breast tissue should be regarded with the same oncologic principle as female
      breast tissue. In cases in which ultrasound-assisted suction lipectomy is used,
      the inability to analyze the breast tissue should be disclosed to the patient.

PMID- 17522494
TI  - Management of a total parotidectomy defect with a gastrocnemius muscle transfer
      and vascularized sural nerve grafting.
AB  - Immediate facial nerve reconstruction is very demanding after total
      parotidectomy. Under such conditions, we reconstructed facial nerves using
      vascularized sural nerve with free lateral gastrocnemius muscle flap. The patient
      was a 14-year-old male diagnosed with mucoepidermoid carcinoma of the right
      parotid gland. We reconstructed zygomatic, buccal, and mandibular branches of
      facial nerve using 2 vascularized sural nerves, medial sural cutaneous nerve, and
      the lateral sural cutaneous nerve. The postoperative course was good, and there
      was no flap trouble. The reinnervated nerve recovered from 3 months after the
      operation. In 6 months after operation, almost normal animation was recovered,
      except for the corners of the patient's mouth. The advantages of this flap are
      feasible harvesting in the supine position, feasible filling of the dead space,
      possible harvesting of 2 series of lateral sural cutaneous nerve and median sural
      cutaneous nerve, and less sacrifice of the donor site. The disadvantage of this
      method is that the diameter of the pedicle is smaller than that of the medial
      pedicle. But the diameters of the lateral sural artery and vein are suitable to
      anastomose the cervical artery and vein. This flap is one of the good options for
      reconstruction of facial nerves after total parotidectomy.

PMID- 17522495
TI  - Irreducible distal interphalangeal joint dislocation: a case report and
      literature review.
AB  - We present a case of an irreducible dorsal distal interphalangeal joint
      dislocation caused by dislocation of the flexor digitorum profundus tendon.
      Although these types of injuries are rare, through a search of the literature, we
      conclude that a high degree of suspicion must be maintained in irreducible
      dislocations for this type of injury. An early open approach for diagnosis and
      treatment is recommended.

PMID- 17522496
TI  - Aberrant course of a communicating branch of the ulnar nerve to the median nerve
      contributing to hypothenar Hammer syndrome.
AB  - This presentation represents a unique anatomic predisposition to the development
      of hypothenar hammer syndrome (HHS). In this case, a communicating branch of the
      ulnar nerve to the median common digital nerve of the ring finger was identified
      crossing volar to the superficial palmar arch. This relationship caused
      thrombosis of the superficial palmar arch proximal to this crossing nerve branch.
      The aberrant course of this nerve created a structural anomaly contributing to
      HHS, which ultimately mandated surgical intervention.

PMID- 17522497
TI  - The reverse sural artery adipofasciomuscular flap for the reconstruction of a
      heel sinus with underlying calcaneal osteomyelitis.
AB  - The reverse sural artery fasciomusculocutaneous flap has become an acceptable
      technique of lower-limb reconstruction despite the grafted appearance of the
      donor site in the upper leg. In an attempt to reduce the donor-site morbidity, we
      describe the use of the adipofasciomuscular reverse sural artery flap in a
      patient with a heel sinus and underlying calcaneal osteomyelitis.

PMID- 17522498
TI  - Abdominal wall endometrioma: case report and review.
AB  - Women with chronic, cyclical abdominal wall pain after gynecologic surgery may
      present in the plastic surgeon's office requesting body contouring. We present
      one such case in which an abdominal wall endometrioma was found. Resection of the
      endometrioma with the abdominal panniculus resulted in symptomatic cure for the
      patient. Plastic surgeons should be aware of the association of endometriosis
      with chronic pelvic/abdominal pain. Furthermore, suspicion of abdominal wall
      endometrioma should be entertained when patients present with chronic
      intermittent or cyclical abdominal wall pain after surgery of the pelvis or
      abdomen, especially after gynecologic or obstetric procedures.

PMID- 17522499
TI  - Transfer of pedicled musculocutaneous latissimus dorsi flap for restoration of
      shoulder contour after neurogenic atrophy.
AB  - Neurogenic atrophy of the deltoid muscle due to brachial plexus injury will lead
      to a disfiguring deformity of the shoulder contour, apart from the functional
      deficit. When there is no possibility for functional restoration of the shoulder
      movement, this contour defect will become the patient's major concern. We present
      a new method in which the ipsilateral latissimus dorsi muscle was used as a
      pedicled musculocutaneous flap to augment the shoulder contour in 3 patients. In
      all patients, there was a concomitant lesion to the thoracodorsal nerve, with
      subsequent palsy of the latissimus dorsi muscle. Therefore, donor-site morbidity
      was minimal. The final esthetic appearance was pleasing, and the patient
      satisfaction was quite high.

PMID- 17522500
TI  - Rapid 3-dimensional anthropometry by semiautomatic data acquisition and
      processing.
AB  - A semiautomatic anthropometric caliper was developed to accelerate and simplify
      anthropometric data acquisition. A technical slide caliper, connected via optical
      data cable interface to a standard PC, was amended with a data-input switch. A
      data sheet was filled in with consecutive measurements in 30 volunteers and
      compared with 30 fully manually performed and transmitted examinations on the
      identical volunteer population. To examine the reliability of the semiautomatic
      measurements, repeat measurements were performed interindividually and
      intraindividually in 10 volunteers. The time required for a cephalometric
      measurement routine was reduced from 16 +/- 3 minutes to 6 +/- 2 minutes. The
      intraindividual standard/relative error was reduced from 2.1 +/- 1.9% to 1.4 +/-
      1.7%, interindividually from 3.2 +/- 2.1% to 2.2 +/- 0.9%. The presented
      semiautomatic anthropometric caliper promises to be faster and reliable for
      anthropometric measurements of craniofacial conformation and will prospectively
      become applied for growth and treatment control. The relative measurement error
      seems to be smaller than in full-manual assessment; oversight error in manual
      recording can moreover be excluded effectively.

PMID- 17522501
TI  - In the beginning.

PMID- 17522502
TI  - The value of the internal mammary perforator branches as a new perforator flap.

PMID- 17522504
TI  - Measuring the surface area of surgical lesions.

PMID- 17522505
TI  - An easy way of obtaining symmetry in auricular surgery using a mirror.

PMID- 17522506
TI  - A randomized, controlled trial of postoperative adjuvant interferon therapy after
      resection of hepatocellular carcinoma.
AB  - OBJECTIVE: We conducted a randomized controlled trial of adjuvant interferon
      therapy in patients with predominantly hepatitis B-related hepatocellular
      carcinoma (HCC) to investigate whether the prognosis after hepatic resection
      could be improved. SUMMARY BACKGROUND DATA: Recurrence is common after hepatic
      resection for HCC. Interferon possesses antiviral, immunomodulatory,
      antiproliferative, and antiangiogenic effects and may be an effective form of
      adjuvant therapy. PATIENTS AND METHODS: Since February 1999, patients with no
      residual disease after hepatic resection for HCC were randomly assigned with
      stratification by pTNM stage to receive no treatment (control group), interferon
      alpha-2b 10 MIU/m (IFN-I group) or 30 MIU/m (IFN-II group) thrice weekly for 16
      weeks. Enrollment to the IFN-II group was terminated from January 2000 because
      adverse effects resulted in treatment discontinuation in the first 6 patients. By
      June 2002, 40 patients each had been enrolled into the control group and IFN-I
      group. The baseline clinical, laboratory, and tumor characteristics of both
      groups were comparable. RESULTS: The 1- and 5-year survival rates were 85% and
      61%, respectively, for the control group and 97% and 79%, respectively, for the
      IFN-I group (P = 0.137). After adjusting for the confounding prognostic factors
      in a Cox model, the relative risk of death for interferon treatment was 0.42 (95%
      CI, 0.17-1.05; P = 0.063). Exploratory subset analysis showed that adjuvant
      interferon had no survival benefit for pTNM stage I/II tumor (5-year survival 90%
      in both groups; P = 0.917) but prevented early recurrence and improved the 5-year
      survival of patients with stage III/IVA tumor from 24% to 68% (P = 0.038).
      CONCLUSION: In a group of patients with predominantly hepatitis B-related HCC,
      adjuvant interferon therapy showed a trend for survival benefit, primarily in
      those with pTNM stage III/IVA tumors. Further larger randomized trials stratified
      for stage are needed.

PMID- 17522507
TI  - Interferon: the magic bullet to prevent hepatocellular carcinoma recurrence after
      resection?

PMID- 17522508
TI  - Prospective randomized study comparing sentinel lymph node evaluation with
      standard pathologic evaluation for the staging of colon carcinoma: results from
      the United States Military Cancer Institute Clinical Trials Group Study GI-01.
AB  - BACKGROUND: The principal role of sentinel lymph node (SLN) sampling and
      ultrastaging in colon cancer is enhanced staging accuracy. The utility of this
      technique for patients with colon cancer remains controversial. PURPOSE: This
      multicenter randomized trial was conducted to determine if focused assessment of
      the SLN with step sectioning and immunohistochemistry (IHC) enhances the ability
      to stage the regional nodal basin over conventional histopathology in patients
      with resectable colon cancer. PATIENTS AND METHODS: Between August 2002 and April
      2006 we randomly assigned 161 patients with stage I-III colon cancer to standard
      histopathologic evaluation or SLN mapping (ex vivo, subserosal, peritumoral, 1%
      isosulfan blue dye) and ultrastaging with pan-cytokeratin IHC in conjunction with
      standard histopathology. SLN-positive disease was defined as individual tumor
      cells or cell aggregates identified by hematoxylin and eosin (H&E) and/or IHC.
      Primary end point was the rate of nodal upstaging. RESULTS: Significant nodal
      upstaging was identified with SLN ultrastaging (Control vs. SLN: 38.7% vs. 57.3%,
      P = 0.019). When SLNs with cell aggregates < or =0.2 mm in size were excluded, no
      statistically significant difference in node-positive rate was apparent between
      the control and SLN arms (38.7% vs. 39.0%, P = 0.97). However, a 10.7% (6/56)
      nodal upstaging was identified by evaluation of H&E stained step sections of SLNs
      among study arm patients who would have otherwise been staged node-negative (N0)
      by conventional pathologic assessment alone. CONCLUSION: SLN mapping, step
      sectioning, and immunohistochemistry (IHC) identifies small volume nodal disease
      and improves staging in patients with resectable colon cancer. A prospective
      trial is ongoing to determine the clinical significance of colon cancer
      micrometastasis in sentinel lymph nodes.

PMID- 17522509
TI  - Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial.
AB  - INTRODUCTION: The clinical impact of sentinel lymph node biopsy (SLNB) in colon
      cancer is still controversial. The purpose of this prospective multicenter trial
      was to evaluate its clinical value to predict the nodal status and identify
      factors that influence these results. METHODS: Colon cancer patients without
      prior colorectal surgery or irradiation were eligible. The sentinel lymph node
      (SLN) was identified intraoperatively by subserosal blue dye injection around the
      tumor. The SLN underwent step sections and immunohistochemistry (IHC), if
      classified free of metastases after routine hematoxylin and eosin examination.
      RESULTS: At least one SLN (median, n = 2) was identified in 268 of 315 enrolled
      patients (detection rate, 85%). Center experience, lymphovascular invasion, body
      mass index (BMI), and learning curve were positively associated with the
      detection rate. The false-negative rate to identify pN+ patients by SLNB was 46%
      (38 of 82). BMI showed a significant association to the false-negative rate (P <
      0.0001), the number of tumor-involved lymph nodes was inversely associated. If
      only slim patients (BMI < or =24) were investigated in experienced centers (>22
      patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21%
      (30 of 141) of the patients, classified as pN0 by routine histopathology,
      revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN.
      CONCLUSIONS: The contribution of SLNB to conventional nodal staging of colon
      cancer patients is still unspecified. Technical problems have to be resolved
      before a definite conclusion can be drawn in this regard. However, SLNB
      identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes.
      Further studies must clarify the clinical impact of these findings in terms of
      prognosis and the indication of adjuvant therapy.

PMID- 17522510
TI  - Close collaboration between surgeon and pathologist is essential for accurate
      staging of early colon cancer.

PMID- 17522511
TI  - A prospective randomized controlled trial of multimodal perioperative management
      protocol in patients undergoing elective colorectal resection for cancer.
AB  - OBJECTIVE: A prospective randomized controlled trial (RCT) of multimodal
      perioperative management protocol in patients undergoing elective colorectal
      resection for cancer. AIMS: This study evaluates the use of a multimodal package
      in colorectal cancer surgery in the context of an RCT. METHODS: Patients for
      elective resection for colorectal cancer were offered trial entry. Participants
      were stratified by sex and requirement for a total mesorectal excision and
      centrally randomized. Multimodal patients received intravenous fluid restriction,
      unrestricted oral intake with prokinetic agents, early ambulation, and fixed
      regimen epidural analgesia. Control patients received intravenous fluids to
      prevent oliguria, restricted oral intake until return of bowel motility, and
      weaning regimen epidural analgesia. Adherence to both regimens was reinforced
      using a daily checklist and protocol guidance sheets. Discharge decision was made
      using pre-agreed criteria. The primary endpoint was postoperative stay, and
      achievement of independence milestones. Secondary endpoints were postoperative
      complications, readmission rates, and mortality. Analysis was by intention to
      treat. RESULTS: Seventy patients were recruited. Approximately one fourth
      underwent TME. Median ages were similar (69.3 vs. 73.0 years). The median stay
      was significantly reduced in the multimodal group (5 vs. 7 days; P < 0.001, Mann
      Whitney U test). Patients in the control arm were 2.5 times as likely to require
      a postoperative stay of more than 5 days. Patients in the multimodal group had
      less cardiorespiratory and anastomotic complications but more readmissions. There
      were 2 deaths, both controls. CONCLUSIONS: This RCT provides level 1b evidence
      that a multimodal management protocol can significantly reduce postoperative stay
      following colorectal cancer surgery. Morbidity and mortality are not increased.

PMID- 17522512
TI  - CDH1 truncating mutations in the E-cadherin gene: an indication for total
      gastrectomy to treat hereditary diffuse gastric cancer.
AB  - BACKGROUND: Approximately 1% to 3% of all gastric cancers are associated with
      families exhibiting an autosomal dominant pattern of susceptibility. E-cadherin
      (CDH1) truncating mutations have been shown to be present in approximately 30% of
      families with hereditary diffuse gastric cancer (HDGC) and are associated with a
      significantly increased risk of gastric cancer and lobular breast cancer.
      METHODS: Individuals from a large kindred with HDGC who were identified to have a
      CDH1 mutation prospectively underwent comprehensive screening with stool occult
      blood testing, standard upper gastrointestinal endoscopy with random gastric
      biopsies, high-magnification endoscopy with random gastric biopsies, endoscopic
      ultrasonography, CT, and PET scans to evaluate the stomach for occult cancer.
      Subsequently, they each underwent total gastrectomy with D-2 node dissection and
      Roux-en-Y esophagojejunostomy. The stomach and resected lymph nodes were
      evaluated pathologically. RESULTS: Six patients were identified as CDH1 carriers
      from a single family. There were 2 men and 4 women. The mean age was 54 years
      (range, 51-57 years). No patient had any signs or symptoms of gastric cancer.
      Exhaustive preoperative stomach evaluation was normal in each case, and the
      stomach and adjacent lymph nodes appeared normal at surgery. However, each
      patient (6 of 6, 100%) was found to have multiple foci of T1 invasive diffuse
      gastric adenocarcinoma (pure signet-ring cell type). No patient had lymph node or
      distant metastases. Each was staged as T1N0M0. Each patient recovered
      uneventfully without morbidity or mortality. CONCLUSIONS: CDH1 mutations in
      individuals from families with HDGC are associated with gastric cancer in a
      highly penetrant fashion. CDH1 mutations are an indication for total gastrectomy
      in these patients. This mutation will identify patients with cancer before other
      detectable symptoms or signs of the disease.

PMID- 17522513
TI  - Bile acids and total bilirubin detection in saliva of patients submitted to
      gastric surgery and in particular to subtotal Billroth II resection.
AB  - OBJECTIVE: The aim of our study was to detect bile acids and total bilirubin in
      saliva of gastrectomized patients, to confirm objectively presence of biliary
      laryngopharyngeal reflux and its relationship with laryngeal mucosa damage.
      SUMMARY BACKGROUND DATA: Recently, it has been hypothesized that biliary-reflux
      may reach the upper aerodigestive tract and enhance development of laryngeal
      malignancies; nevertheless, the presence of duodenogastric contents in this
      region has never been revealed. METHODS: We carried out a prospective
      observational case-control study on 52 patients (cases) previously submitted to
      gastric surgery, mainly to subtotal Billroth II resection, and on 51 healthy
      volunteers (controls). Patients were submitted to clinical interview,
      esophagogastroduodenal endoscopy, endoscopic laryngeal evaluation, and saliva
      collection. In all saliva samples, bile acids, total bilirubin, and pepsinogen II
      were assayed. RESULTS: In cases, group bile acids levels were recorded in 17 of
      52 (32.6%) patients, while in 35 of 52 (67.4%) they were undetectable. All
      controls were negative to bile acids. In positive cases to bile acids, we found a
      significant (P < 0.05) correlation between bile acids, total bilirubin, and
      pepsinogen II values and a significant (P < 0.05) higher prevalence of symptoms
      and findings of laryngeal damage and of previous laryngeal neoplastic lesions.
      CONCLUSIONS: We found detectable levels of bile acids and total bilirubin in
      saliva of patients submitted to previous gastric surgery, prospecting an
      intriguing diagnostic role of this dosage in the study of biliary
      laryngopharyngeal reflux. We finally revealed a high incidence of laryngeal
      disorders in patients with positive bile acids in saliva.

PMID- 17522514
TI  - Disconnect between incidence of nonperforated and perforated appendicitis:
      implications for pathophysiology and management.
AB  - OBJECTIVE: Appendicitis has been declining in frequency for several decades.
      During the past 10 years, its preoperative diagnosis has been made more reliable
      by improved computed tomography (CT) imaging. Thresholds for surgical exploration
      have been lowered by the increased availability of laparoscopic exploration.
      These innovations should influence the number of appendectomies performed in the
      United States. We analyzed nationwide hospital discharge data to study the
      secular trends in appendicitis and appendectomy rates. METHODS: All appendicitis
      and appendiceal operations reported to the National Hospital Discharge Survey
      (NHDS) 1970-2004 were classified as perforated, nonperforated, negative, and
      incidental appendectomies and analyzed over time and by various demographic
      measures. Secular trends in the population-based incidence rates of nonperforated
      and perforated appendicitis and negative and incidental appendectomy were
      examined. RESULTS: Nonperforated appendicitis rates decreased between 1970 and
      1995 but increased thereafter. The 25-year decreasing trend was accounted for
      almost entirely by a decreasing incidence in the 10-19 year age group. The rise
      after 1995 occurred in all age groups above 5 years and paralleled increasing
      rates of CT imaging and laparoscopic surgery on the appendix. Since 1995 the
      negative appendectomy rate has been falling, especially in women, and incidental
      appendectomies, frequent in prior decades, have been rarely performed. Despite
      these large changes, the rate of perforated appendicitis has increased steadily
      over the same period. Although perforated and nonperforated appendicitis rates
      were correlated in men, they were not significantly correlated in women nor were
      there significant negative correlations between perforated and negative
      appendectomy rates. CONCLUSION: The 25-year decline in nonperforated appendicitis
      and the recent increase in appendectomies coincident with more frequent use of CT
      imaging and laparoscopic appendectomies did not result in expected decreases in
      perforation rates. Similarly, time series analysis did not find a significant
      negative relationship between negative appendectomy and perforation rates. This
      disconnection of trends suggests that perforated and nonperforated appendicitis
      may have different pathophysiologies and that nonoperative management with
      antibiotic therapy may be appropriate for some initially nonperforated cases.
      Further efforts should be directed at identifying preoperative characteristics
      associated with nonperforating appendicitis that may eventually allow surgeons to
      defer operation for those cases of nonperforating appendicitis that have a low
      perforation risk.

PMID- 17522515
TI  - Gallbladder cancer: the role of laparoscopy and radical resection.
AB  - OBJECTIVES: We assess how laparoscopy has altered the presentation of patients
      with gallbladder cancer and determine whether radical resection in patients with
      gallbladder cancer is beneficial. SUMMARY BACKGROUND DATA: The widespread
      adoption of laparoscopic cholecystectomy has led to an increased frequency of
      incidentally discovered gallbladder carcinoma. Little data exist to guide
      surgeons in the optimum management of patients with gallbladder cancer,
      particularly with respect to the potential advantages of radical resection.
      METHODS: Records of 107 patients with gallbladder cancer admitted to a tertiary
      academic medical center between 1995 and 2004 were reviewed. Gallbladder cancer
      was found incidentally in 53 patients (50%). Fifty-two of these patients
      underwent a routine laparoscopic cholecystectomy and were found to have
      gallbladder cancer intraoperatively or following the operation by subsequent
      pathologic evaluation of the specimen. Gallbladder cancer had been diagnosed
      preoperatively by radiology in the other 54 patients (50%). These patients did
      not undergo laparoscopic cholecystectomy and were explored electively. RESULTS:
      The median age at presentation was 67 years and 66% were female. Patients who
      were found to have gallbladder carcinoma incidentally at laparoscopic
      cholecystectomy had a significant increase in survival when compared with those
      who were admitted electively with a known diagnosis (P < 0.001). All patients who
      presented with a known diagnosis had stage II or greater disease, and 36% of
      these were stage IV carcinomas. However, 82% of those patients who were found
      incidentally were stage I or II. The overall 5-year survival for all patients was
      15%; those discovered incidentally at laparoscopic cholecystectomy had a 5-year
      survival of 33%. This difference was significant among patients with stage II
      carcinomas. In the laparoscopic group, there was no difference in survival
      between the patients who were immediately converted to an open resection when
      identified to have gallbladder cancer intraoperatively (n = 6) and those who had
      a completed laparoscopic cholecystectomy and were re-explored at a later point
      when found to have gallbladder cancer by subsequent pathology (n = 33). There was
      a significant improvement in survival in 50 patients (47%) who underwent some
      form of radical resection (P < 0.001). Stage for stage comparison showed that
      this was significant in stage II disease. Patients who underwent hepatic
      resection along with lymphadenectomy and extra hepatic biliary resection had
      similar survival compared with those who had hepatic resection and
      lymphadenectomy alone. CONCLUSIONS: Laparoscopic cholecystectomy appears to have
      resulted in the earlier discovery of gallbladder cancer in some patients,
      resulting in increased probability of survival. Patients discovered with
      gallbladder carcinoma during a laparoscopic cholecystectomy do not have to be
      converted immediately to an open resection and should be referred to a tertiary
      care center for further exploration. Adjunctive radical surgical resection,
      either at the time of cholecystectomy or subsequently, increases survival
      significantly in early stage disease.

PMID- 17522516
TI  - Modification of acid-base balance in cirrhotic patients undergoing liver
      resection for hepatocellular carcinoma.
AB  - OBJECTIVE: To examine modifications of acid-base balance of cirrhotic patients
      undergoing hepatectomy for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND
      DATA: Acid-base disorders are frequently observed in cirrhotics; however,
      modifications during hepatectomy and their impact on prognosis have never been
      investigated. METHODS: Two hundred and two hepatectomies for HCC on cirrhosis
      were reviewed. Arterial blood samples were collected immediately before and at
      the end of resection. Preresection and postresection acid-base parameters were
      compared and related to patient characteristics and postoperative course. The
      accuracy of acid-base parameters in predicting postoperative liver failure,
      defined as an impairment of liver function after surgery that led to patient
      death or required transplantation, was assessed using receiver operating
      characteristic analysis (ROC). RESULTS: All patients showed a significant
      reduction in pH, bicarbonate, and base excess at the end of hepatectomy (P <
      0.001 in all cases), worsened by intraoperative blood loss (P < 0.010) and
      preoperative Model for end-stage liver disease score > or =11 (P < 0.010). ROC
      curve analysis identifies patients with postresection bicarbonate <19.4 mmol/L at
      high risk for liver failure (50.0%) whereas levels >22.1 mmol/L did not lead to
      the event (0%; P < 0.001). Postoperative prolongation of prothrombin time and
      increases in bilirubin, creatinine, and morbidity were also more frequent in
      patients with lower postresection bicarbonate, resulting in a longer in-hospital
      stay. CONCLUSION: In cirrhotic patients, a trend toward a relative acidosis can
      be expected during surgery and is worsened by the severity of the underlying
      liver disease and intraoperative blood loss. Postresection bicarbonate level
      lower than 19.4 mmol/L is an adverse prognostic factor.

PMID- 17522517
TI  - Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC
      TNM systems in a cohort of 13,772 patients in Japan.
AB  - OBJECTIVE: The aims of this study were to present evidence to develop and
      validate the Japanese Tumor-Node-Metastasis (TNM) staging system for primary
      liver cancer and to compare its discriminatory ability and predictive power with
      those of Vauthey's simplified staging, which was adopted as the TNM staging
      system of the American Joint Committee on Cancer (AJCC)/International Union
      Against Cancer (UICC). SUMMARY BACKGROUND DATA: Among many staging systems for
      hepatocellular carcinoma, the Japanese TNM staging system and the AJCC/UICC
      staging system were developed based on a survival analysis of surgical patients.
      These 2 staging systems have not been compared in large series. METHODS: The
      Liver Cancer Study Group of Japan (LCSGJ) prospectively collected
      clinicopathologic data of 63,736 patients with primary liver cancer from 1995 to
      2001. Among them, 13,772 patients received curative hepatic resection. Based on
      univariate and multivariate survival analyses, the Japanese TNM staging system
      was developed. The accuracy of the Japanese TNM staging system for predicting
      patient survival was compared with that of the AJCC/UICC staging system using the
      cross-validation method. RESULTS: The independent prognostic factors (relative
      risk; 95% confidence interval) were vascular or bile duct invasion (1.36;1.29
      1.43), liver cirrhosis (1.26;1.20-1.32), diameter (< or =2 cm or >2 cm)
      (1.21;1.14-1.28), alpha-fetoprotein (1.20;1.15-1.25), single/multiple (1.18;1.12
      1.23), liver damage (1.15;1.10-1.20), hepatic involvement (1.14;1.09-1.19),
      histologic differentiation (1.14;1.08-1.20), gross classification (1.13;1.08
      1.18), and esophageal varices (1.07;1.02-1.13). Based on these results, 3
      criteria (vascular or bile duct invasion, diameter, and single/multiple) were
      selected. Patients with none of these 3 factors were considered T1, and those
      with 1, 2, and 3 factors were T2, T3, and T4, respectively. The number of
      patients and 5-year survival rates for T1, T2, T3, and T4 were 2078, 70%; 6853,
      58%; 3021, 41%; and 582, 24% (P < 0.0001), respectively, while those for the AJCC
      T were 8457, 61% in T1, 2888, 46% in T2, and 1189, 30% in T3 (P < 0.0001). While
      both the LCSGJ-T and the AJCC-T had good discriminating ability, the former was
      significantly superior (P = 0.0007). CONCLUSIONS: Our findings support the
      development of LCSG stage. While both staging systems allow for the clear
      stratification of patients into prognostic groups, the LCSGJ staging may be more
      appropriate for stratifying patients with early-stage HCC.

PMID- 17522518
TI  - Hepatic steatosis is a risk factor for postoperative complications after major
      hepatectomy: a matched case-control study.
AB  - OBJECTIVE: To assess the impact of microsteatosis (MiS) and macrosteatosis (MaS)
      on major hepatectomy. SUMMARY BACKGROUND DATA: While steatosis of a liver graft
      is an established risk factor in transplantation, its impact on major hepatectomy
      remains unclear. METHODS: Fifty-eight steatotic patients who underwent major
      hepatectomy were matched 1:1 with patients with normal liver according to age,
      gender, ASA score, diagnosis, extent of hepatectomy, and need of
      hepaticojejunostomy. Steatosis was evaluated quantitatively and qualitatively.
      Primary endpoints were mortality and complications. RESULTS: Pure MaS and MiS
      were present in only 10 and 3 patients, respectively, while mixed steatosis was
      noted in 45 patients. Forty-four patients had mild (10%-30%) and 14
      moderate/severe (>30%) steatosis. Steatotic patients had significantly higher
      serum transaminase and bilirubin levels, and lower prothrombin time. Blood loss
      (P = 0.04) and transfusions (P = 0.03), and ICU stay (P = 0.001) were increased
      in steatotic patients. Complications were higher in steatotic patients when
      considered either overall (50% vs. 25%, P = 0.007) or major (27.5% vs. 6.9%, P =
      0.001) complications. Patients with pure MaS had increased mortality (MaS: 20%
      vs. MiS: 6.6% vs. mixed: 0%; P = 0.36) and major complications (MaS: 66% vs. MiS:
      50% vs. mixed: 24%; P = 0.59), but not significantly. Preoperative cholestasis
      was a highly significant risk factor for mortality in patients with hepatic
      steatosis. CONCLUSION: Steatosis per se is a risk factor for postoperative
      complications after major hepatectomy and should be considered in the planning of
      surgery. Caution must be taken to perform major hepatectomy in steatotic patients
      with preexisting cholestasis.

PMID- 17522519
TI  - Heme oxygenase-1 induction by the clinically used anesthetic isoflurane protects
      rat livers from ischemia/reperfusion injury.
AB  - OBJECTIVE: It was the aim of this study to characterize the influence of
      isoflurane-induced heme oxygenase-1 (HO-1) expression on hepatocellular integrity
      after ischemia and reperfusion. SUMMARY BACKGROUND DATA: Abundant experimental
      data characterize HO-1 as one of the most powerful inducible enzymes that
      contribute to the protection of the liver and other organs after harmful stimuli.
      Therapeutic strategies aimed at utilizing the protective effects of HO-1 are
      hampered by the fact that most pharmacological inducers of this enzyme perturb
      organ function by themselves and are not available for use in patients because of
      their toxicity and undesirable or unknown side effects. METHODS: Rats were
      pretreated with isoflurane before induction of partial hepatic ischemia (1 hour)
      and reperfusion (1 hour). At the end of each experiment, blood and liver tissue
      were obtained for molecular biologic, histologic, and immunohistochemical
      analyses. RESULTS: Isoflurane pretreatment increased hepatic HO-1 mRNA, HO-1
      protein, HO enzyme activity, and decreased plasma levels of AST, ALT, and alpha
      GST. Histologic analysis of livers obtained from isoflurane-pretreated rats
      showed a reduction of necrotic areas, particularly in the perivenular region, the
      predominant site of isoflurane-induced HO-1 expression. In addition, sinusoidal
      congestion that could otherwise be observed after ischemia/reperfusion was
      inhibited by the anesthetic. Furthermore, isoflurane augmented hepatic
      microvascular blood flow and lowered the malondialdehyde content within the liver
      compared with control animals. Administration of tin protoporphyrin IX inhibited
      HO activity and abolished the isoflurane-induced protective effects. CONCLUSIONS:
      This study provides first evidence that pretreatment with the nontoxic and
      clinically approved anesthetic isoflurane induces hepatic HO-1 expression, and
      thereby protects rat livers from ischemia/reperfusion injury.

PMID- 17522520
TI  - Peroral endoscopic drainage/debridement of walled-off pancreatic necrosis.
AB  - BACKGROUND: Experience with minimal access, transoral/transmural endoscopic
      drainage/debridement of walled-off pancreatic necrosis (WOPN) after necrotizing
      pancreatitis is limited. We sought to determine outcome using this technique.
      METHODS: Retrospective analysis. RESULTS: From 1998 to 2006, 53 patients
      underwent transoral/transmural endoscopic drainage/debridement of sterile (27,
      51%) and infected (26, 49%) WOPN. Intervention was performed a median of 49 days
      (range, 20-300 days) after onset of acute necrotizing pancreatitis. A median of 3
      endoscopic procedures/patient (range, 1-12) were performed. Twenty-one patients
      (40%) required concurrent radiologic-guided catheter drainage of associated or
      subsequent areas of peripancreatic fluid and/or WOPN. Twelve patients (23%)
      required open operative intervention a median of 47 days (range, 5-540) after
      initial endoscopic drainage/debridement, due to persistence of WOPN (n = 3),
      recurrence of a fluid collection (n = 2), cutaneous fistula formation (n = 2), or
      technical failure, persistence of pancreatic pain, colonic obstruction,
      perforation, and flank abscess (n = 1 each). Final outcome after initial
      endoscopic intervention (median, 178 days) revealed successful endoscopic therapy
      in 43 (81%) and persistence of WOPN in 10 (19%). Preexistent diabetes mellitus,
      size of WOPN, and extension of WOPN into paracolic gutter were significant
      predictive factors for need of subsequent open operative therapy. CONCLUSIONS:
      Successful resolution of symptomatic, sterile, and infected WOPN can be achieved
      using a minimal access endoscopic approach. Adjuvant percutaneous drainage is
      necessary in up to 40% of patients, especially when WOPN extends to paracolic
      gutters or pelvis. Operative intervention for failed endoscopic treatment is
      required in about 20% of patients.

PMID- 17522521
TI  - Should soft tissue sarcomas be treated at high-volume centers? An analysis of
      4205 patients.
AB  - OBJECTIVE: : To define the prognostic significance of surgical center case volume
      on outcome for soft tissue sarcoma (STS). METHODS: : STS cases registered in the
      Florida Cancer Data System (FCDS) between 1981 and 2001 were analyzed. Medical
      facilities were ranked by STS operative volume. Facilities above the 67th
      percentile for volume were defined as high-volume centers (HVCs). RESULTS: : Of
      the 4205 operative cases of STS identified, 68.1% were treated at low-volume
      centers (LVCs) and 31.9% at HVCs. A larger proportion of high-grade tumors (53.8%
      vs. 44.3%) and lesions over 10 cm (40.7% vs. 28.7%) were resected at HVC (P <
      0.001). The 30-day mortality was 0.7% for HVC and 1.5% for LVC (P = 0.028), and
      mortality rates at 90 days were 1.6% and 3.6%, respectively (P = 0.001). Median
      survival was 40 months at HVC and 37 months at LVC (P = 0.002). Univariate
      analysis demonstrated significantly improved survival at HVC for high-grade
      tumors (median 30 months vs. 24 months, P = 0.001), lesions over 10 cm (28 months
      vs. 19 months, P = 0.001) and truncal or retroperitoneal sarcomas (39 months vs.
      31 months, P = 0.011). Limb amputation rate was lower (9.4% vs. 13.8%, P = 0.048)
      and radiation and chemotherapy were more frequently administered at HVC (OR =
      1.54). On multivariate analysis, treatment at a HVC was a significant independent
      predictor of improved survival (OR = 1.292, P = 0.047). CONCLUSIONS: : STS
      patients treated at HVC have significantly better survival and functional
      outcomes. Patients with either large (>10 cm), high-grade or
      truncal/retroperitoneal tumors should be treated exclusively at a high-volume
      center.

PMID- 17522522
TI  - The utility of intraoperative bilateral internal jugular venous sampling with
      rapid parathyroid hormone testing.
AB  - OBJECTIVE: To determine the utility of routine perioperative bilateral internal
      jugular venous sampling of parathyroid hormone (BIJ PTH) for localization during
      parathyroid surgery. SUMMARY BACKGROUND DATA: Venous sampling for PTH is a useful
      tool for parathyroid localization in patients undergoing reoperative surgery for
      hyperparathyroidism (HPT). With the development of intraoperative rapid PTH
      (ioPTH) testing, internal jugular PTH sampling with ioPTH testing to guide
      operative localization has been shown to be possible in select, difficult cases.
      However, the value of BIJ PTH for patients with HPT is unclear. METHODS: Between
      May 2004 and February 2006, 216 consecutive patients underwent neck exploration
      for HPT by one surgeon. Of these, 168 patients had BIJ PTH. Internal jugular
      venous blood was drawn from both left and right sides and analyzed for PTH using
      a rapid PTH assay. BIJ PTH levels were defined as lateralizing if >5% differences
      were observed between the right and left internal jugular vein samples. RESULTS:
      Of the 168 patients, 120 (71.4%) had a single parathyroid adenoma, 15 (8.9%) had
      double adenoma, and 33 (19.6%) had hyperplasia. The cure rate after
      parathyroidectomy was 98.2%. There were no complications related to BIJ PTH
      sampling. Sensitivity and positive predictive value of BIJ PTH for primary
      hyperparathyroidism were 80% and 71%, respectively. BIJ PTH was diagnostic in 95
      cases (62.9%) in primary HPT. BIJ PTH successfully localized an abnormal gland in
      26 of 45 (57.8%) in patients with negative sestamibi scanning. BIJ PTH was
      especially helpful in 18 of 168 (10.7%) cases when intraoperative peripheral
      parathyroid hormone did not fall by 50% and BIJ PTH successfully localized the
      hyperfunctioning glands. CONCLUSIONS: In patients with HPT, BIJ PTH is safe and
      effective, providing additional localization information in the majority of
      cases. BIJ PTH is particularly useful in the setting of negative sestamibi
      scanning and in complex multigland disease cases.

PMID- 17522523
TI  - Transient receptor potential vanilloid 1 antagonist, capsazepine, improves
      survival in a rat hemorrhagic shock model.
AB  - OBJECTIVE: To evaluate the role of transient receptor potential vanilloid 1
      (TRPV1) in a rat hemorrhagic shock (HS) model using the TRPV1 antagonist,
      capsazepine (CPZ). SUMMARY BACKGROUND DATA: TRPV1, distributed within the sensory
      nerve, plays a role in the regulation of cardiovascular functions. TRPV1 may be
      involved in the cardiovascular responses to HS. METHODS: Male rats were
      anesthetized and HS was induced with the mean arterial pressure (MAP) at 30 mm Hg
      for 90 minutes. CPZ (5.0 micromol/kg) was administered at 30 minutes after the
      shock induction, and the 24-hour survival rates were assessed. The MAP, heart
      rate, and shed blood volume (SBV) were recorded throughout the experiment.
      Arterial blood gas analysis and the plasma catecholamines levels were measured
      before and after HS. Double-immunohistochemistry for Fos and tyrosine hydroxylase
      (TH) was performed in the rostral ventrolateral medulla (RVLM) of the brain.
      RESULTS: CPZ significantly improved the 24-hour survival rates, which was
      accompanied by the increase in the MAP and the SBV, a decrease of the plasma
      catecholamines levels, and attenuation of the severe metabolic acidosis.
      Furthermore, CPZ reduced the percentage of double-labeled neurons for Fos and TH
      in the RVLM of the rat brain. CONCLUSIONS: TRPV1 may be involved in the
      regulation of the cardiovascular responses to HS, at least in part, by recruiting
      catecholaminergic neurons in the RVLM. CPZ appears to induce metabolic
      compensations, which may be potentially useful in HS.

PMID- 17522524
TI  - The PI3K/Akt pathway mediates the nongenomic cardioprotective effects of estrogen
      following trauma-hemorrhage.
AB  - OBJECTIVE: To determine whether the nongenomic actions of E2 have any beneficial
      effect on cardiac function following trauma-hemorrhage and whether those effects
      are mediated via the PI3K/Akt pathway. SUMMARY BACKGROUND DATA: Since studies
      suggest that both genomic and nongenomic pathways are involved in mediating the
      salutary effects of 17beta-estradiol (estradiol) following trauma-hemorrhage, we
      examined if the nongenomic effects of estradiol on cardiac function after trauma
      hemorrhage involve the PI3K/Akt pathway. METHODS: Male Sprague-Dawley rats (
      approximately 300 g) underwent trauma-hemorrhage (mean blood pressure, 40 mm Hg
      for 90 min, then resuscitation). Estradiol conjugated to bovine serum albumin
      (BSA) (estradiol-BSA; 1 mg/kg estradiol) with or without estrogen receptor
      antagonist (ICI 182,780), PI3K inhibitor (Wortmannin), or vehicle was injected
      intravenously during resuscitation. At 2 hours after trauma-hemorrhage or sham
      operation, cardiac output, stroke volume, heart rate, mean arterial pressure, and
      +/-dP/dt were measured. Cardiomyocyte PI3K, p-Akt, Akt protein expressions and
      apoptosis were also determined. One-way ANOVA and Tukey's test were used for
      statistical analysis. RESULTS: Cardiac output, stroke volume, and +/-dP/dt
      decreased significantly after trauma-hemorrhage. Administration of estradiol or
      estradiol-BSA significantly improved these parameters of cardiac function.
      Although trauma-hemorrhage decreased cardiomyocyte PI3K protein expression and
      Akt phosphorylation (p-Akt), estradiol or estradiol-BSA treatment following
      trauma-hemorrhage prevented such decreases in cardiomyocyte PI3K protein
      expressions and p-Akt. The increase in cardiomyocyte apoptosis was also prevented
      in rats receiving estradiol-BSA. Co-administration of ICI 182,780 or Wortmannin
      abolished beneficial effects of estradiol-BSA on cardiac functions following
      trauma-hemorrhage. CONCLUSION: The PI3K/Akt pathway plays a critical role in
      mediating the nongenomic salutary effects of estradiol on cardiac function
      following trauma-hemorrhage.

PMID- 17522525
TI  - Fungal wound infection (not colonization) is independently associated with
      mortality in burn patients.
AB  - OBJECTIVE: To analyze the occurrence of fungal wound infection (FWI) after
      thermal injury and its relationship to mortality. BACKGROUND: FWI is an uncommon
      but potentially lethal complication of severe thermal injury. METHODS: The
      records of patients with thermal burns admitted to a single burn center (1991
      2002) were reviewed. Analyses accounted for total burn size (TBS, percentage body
      surface area), full-thickness burn size (FTBS, percentage body surface area),
      age, inhalation injury, sex, and fungal-status category. Fungal colonization and
      infection were determined histopathologically. RESULTS: Criteria for inclusion
      were met by 2651 patients. Each patient's fungal-status category was defined
      according to the deepest level of fungal involvement observed during the hospital
      course: no fungus (2476 patients), fungal wound colonization (FWC, 121 patients),
      or fungal wound infection (FWI, 54 patients). Median TBS (9%, 47%, 64%,
      respectively) and mortality (5%, 27%, 76%, respectively) varied significantly
      among fungal-status groups. Logistic regression was used to detect significant
      independent associations. FWI was associated with higher TBS. Mortality was
      associated with TBS, FTBS, inhalation injury, FWI, and age. Unlike FWI, FWC was
      not independently related to mortality, the greater observed mortality in FWC
      being explained by other variables such as TBS. The odds ratio for FWI (8.16)
      suggested about the same mortality impact as augmenting TBS by 33%. A midrange
      TBS of 30% to 60% was required for most of the detectable association of FWI with
      mortality. CONCLUSIONS: FWI accompanies larger burns and is associated with
      mortality in burn patients, particularly in those with TBS 30% to 60%. This
      association is independent of burn size, inhalation injury, and age.

PMID- 17522526
TI  - Causes of death in U.S. Special Operations Forces in the global war on terrorism:
      2001-2004.
AB  - BACKGROUND: Effective combat trauma management strategies depend upon an
      understanding of the epidemiology of death on the battlefield. METHODS: A panel
      of military medical experts reviewed photographs and autopsy and treatment
      records for all Special Operations Forces (SOF) who died between October 2001 and
      November 2004 (n = 82). Fatal wounds were classified as nonsurvivable or
      potentially survivable. Training and equipment available at the time of injury
      were taken into consideration. A structured analysis was conducted to identify
      equipment, training, or research requirements for improved future outcomes.
      RESULTS: Five (6%) of 82 casualties had died in an aircraft crash, and their
      bodies were lost at sea; autopsies had been performed on all other 77 soldiers.
      Nineteen deaths, including the deaths at sea were noncombat; all others were
      combat related. Deaths were caused by explosions (43%), gunshot wounds (28%),
      aircraft accidents (23%), and blunt trauma (6%). Seventy of 82 deaths (85%) were
      classified as nonsurvivable; 12 deaths (15%) were classified as potentially
      survivable. Of those with potentially survivable injuries, 16 causes of death
      were identified: 8 (50%) truncal hemorrhage, 3 (19%) compressible hemorrhage, 2
      (13%) hemorrhage amenable to tourniquet, and 1 (6%) each from tension
      pneumothorax, airway obstruction, and sepsis. The population with nonsurvivable
      injuries was more severely injured than the population with potentially
      survivable injuries. Structured analysis identified improved methods of truncal
      hemorrhage control as a principal research requirement. CONCLUSIONS: The majority
      of deaths on the modern battlefield are nonsurvivable. Improved methods of
      intravenous or intracavitary, noncompressible hemostasis combined with rapid
      evacuation to surgery may increase survival.

PMID- 17522527
TI  - An evaluation of the feasibility, validity, and reliability of laparoscopic
      skills assessment in the operating room.
AB  - OBJECTIVE: To assess the use of a synchronized video-based motion tracking device
      for objective, instant, and automated assessment of laparoscopic skill in the
      operating room. SUMMARY BACKGROUND DATA: The assessment of technical skills is
      fundamental to recognition of proficient surgical practice. It is necessary to
      demonstrate the validity, reliability, and feasibility of any tool to be applied
      for objective measurement of performance. METHODS: Nineteen subjects, divided
      into 13 experienced (performed >100 laparoscopic cholecystectomies) and 6
      inexperienced (performed <10 LCs) surgeons completed LCs on 53 patients who all
      had a diagnosis of biliary colic. Each procedure was recorded with the ROVIMAS
      video-based motion tracking device to provide an objective measure of the
      surgeon's dexterity. Each video was also rated by 2 experienced observers on a
      previously validated operative assessment scale. RESULTS: There were significant
      differences for motion tracking parameters between the 2 groups of surgeons for
      the Calot triangle dissection part of procedure for time taken (P = 0.002), total
      path length (P = 0.026), and number of movements (P = 0.005). Both motion
      tracking and video-based assessment displayed intertest reliability, and there
      were good correlations between the 2 modes of assessment (r = 0.4 to 0.7, P <
      0.01). CONCLUSIONS: An instant, objective, valid, and reliable mode of assessment
      of laparoscopic performance in the operating room has been defined. This may
      serve to reduce the time taken for technical skills assessment, and subsequently
      lead to accurate and efficient audit and credentialing of surgeons for
      independent practice.

PMID- 17522528
TI  - Hepatic resection-related hypophosphatemia is of renal origin as manifested by
      isolated hyperphosphaturia.

PMID- 17522529
TI  - Perioperative synbiotic treatment to prevent postoperative infectious
      complications in biliary cancer surgery: a randomized control trial.

PMID- 17522530
TI  - Mental training in surgical education: a randomized controlled trial.

PMID- 17522532
TI  - Recombinant human activated protein C sentenced to the death of a thousand cuts?

PMID- 17522533
TI  - Systemic inflammation and sexual dimorphism: more than meets the eye.

PMID- 17522534
TI  - Transfer surcharge.

PMID- 17522535
TI  - Golden hours wasted: the human cost of intensive care unit and emergency
      department inefficiency.

PMID- 17522536
TI  - Anemic heart: best kept under pressure?

PMID- 17522537
TI  - Antibiotic therapy for community-acquired pneumonia with septic shock: follow the
      guidelines.

PMID- 17522538
TI  - High-frequency oscillation in acute respiratory distress syndrome: who rescues
      the rescuer?

PMID- 17522539
TI  - Critical care services and trial methodology: even at the turning of the tide.

PMID- 17522540
TI  - High-frequency oscillation: how high should we go?

PMID- 17522541
TI  - Endotracheal tube cuff leak: can optimum management of cuff pressure prevent
      pneumonia?

PMID- 17522542
TI  - Optimizing the treatment of a new horseman of the Apocalypse.

PMID- 17522543
TI  - Acidosis and impaired blood coagulation: what and how to correct before using
      recombinant human factor VIIa.

PMID- 17522544
TI  - It is time to pay attention--now more than ever!

PMID- 17522545
TI  - Prerenal azotemia: still a useful concept?

PMID- 17522547
TI  - Referring inhaled nitric oxide and the scientific method.

PMID- 17522548
TI  - Response to the randomized trial of recombinant human erythropoietin in
      critically ill patients.

PMID- 17522549
TI  - N-acetylcysteine as a preventive measure for acute renal failure: a plea for more
      accurate detection of renal function in critically ill patients.

PMID- 17522550
TI  - Moral distress article reflects journal's interdisciplinary respect.

PMID- 17522551
TI  - Muscle weakness after administration of neuromuscular blocking agents: do not
      immobilize the diaphragm unnecessarily.

PMID- 17522552
TI  - Statin therapy and infection-related mortality.

PMID- 17522556
TI  - Violent behavior.

PMID- 17522557
TI  - Managing risk when considering the use of atypical antipsychotics for elderly
      patients with dementia-related psychosis.
AB  - In 2005, responding to several studies, the FDA issued a black box warning on
      atypical (second generation) antipsychotic medications, noting that the drugs may
      increase the risk of cerebrovascular adverse events in elderly patients with
      dementia-related behavior disturbances. The black box warning has raised concern
      for clinicians, among whom atypical antipsychotics have gained favor for having a
      more tolerable side-effect profile than many other pharmacological treatment
      options. Complicating this concern are studies suggesting that other medications
      may have similar risks and a dearth of unbiased head-to-head studies comparing
      different treatment options. To effectively manage risk when treating elderly
      patients with dementia-related psychosis, physicians, patients, and caregivers
      must consider both acute risks (such as danger of bodily harm to the patient and
      others) and long-term risks (such as placement in a restrictive nursing home). If
      an atypical antipsychotic is chosen, additional risk management may be warranted.
      This paper presents a brief overview of relevant concerns and suggests some
      techniques to help minimize and manage risk, such as increased monitoring,
      informed consent, and thorough documentation. A sample clinical risk management
      form and a sample letter to the primary care physician are provided to help guide
      clinicians in improving their risk management practices when working with elderly
      patients suffering from dementia-related psychosis and related behavioral
      difficulties.

PMID- 17522558
TI  - Intermittent psychotherapy: an alternative to continuous long-term treatment for
      patients with personality disorders.
AB  - Open-ended psychotherapies have a limited evidence base for the treatment of
      personality disorders. In patients with personality disorders, in whom pathology
      tends to remit with time, intermittent rather than continuous therapy could be an
      option. Patients might be treated more briefly and then either allowed or
      encouraged to take breaks, while being allowed to return as new issues arise.
      While there are few empirical data on intermittent therapy, it may be common in
      clinical practice. This approach is illustrated by two cases of patients with
      personality disorders seen at multiple points in their lives.

PMID- 17522559
TI  - Intramuscular aripiprazole in the control of agitation.
AB  - OBJECTIVE: To evaluate response to intramuscular (IM) aripiprazole injections
      using secondary analyses from clinical trials. METHODS: Data from one trial in
      patients with bipolar I disorder and two trials in patients with schizophrenia
      were assembled and used for three secondary analyses. Analysis 1 looked at data
      from "nonsedated" patients (i.e., patients with scores < 8 [deep sleep] or 9
      [unarousable] on the Agitation-Calmness Evaluation Scale [ACES]). In analysis 2,
      patients were subdivided into "higher" and "lower" agitation groups according to
      a median split on the baseline score for the Positive and Negative Syndrome Scale
      (PANSS) Excited Component (PEC) (median = 18). Analysis 3 looked at the patients
      who received a second injection within the 24-hour study period. In each
      analysis, the mean change from baseline in PEC scores was re-evaluated. RESULTS:
      Analysis 1 found that nonsedated patients with bipolar I disorder and
      schizophrenia showed significant decreases in PEC scores following treatment with
      aripiprazole IM (p < 0.005). Analysis 2 found that aripiprazole IM significantly
      reduced agitation compared with placebo in patients with bipolar I disorder who
      had lower baseline agitation (p < 0.01), while patients with bipolar I disorder
      who had higher baseline agitation showed similarly large PEC decreases with
      aripiprazole (-9.9) and placebo (-7.9). Patients with schizophrenia showed
      significant reductions in PEC scores compared with placebo regardless of baseline
      level of agitation (p < 0.01). Analysis 3 found that a second injection of
      aripiprazole IM significantly reduced agitation in patients with bipolar I
      disorder or schizophrenia (p < 0.05); repeated injections were safe and well
      tolerated. CONCLUSION: Improvements with aripiprazole IM appeared to be specific
      to core agitation symptoms, as opposed to nonspecific sedation, and to be
      independent of baseline level of agitation. Furthermore, patients benefited from
      a repeated aripiprazole injection when clinically warranted. These results
      address important clinical issues regarding use of aripiprazole IM in treating
      agitation.

PMID- 17522560
TI  - Efficacy and safety of oral aripiprazole compared with haloperidol in patients
      transitioning from acute treatment with intramuscular formulations.
AB  - OBJECTIVE: To report efficacy and safety of transitioning patients receiving
      intramuscular (IM) formulations of aripiprazole or haloperidol to their
      respective oral formulations. METHODS: 448 agitated patients with schizophrenia
      (73%) or schizoaffective disorder (27%) were randomized to receive aripiprazole
      IM 9.75 mg, haloperidol IM 6.5 mg, or placebo IM within 24 hours. Patients
      treated with aripiprazole IM or haloperidol IM who completed this 24-hour IM
      phase were transitioned to the respective blinded oral formulations for 4 days
      (aripiprazole 10-15 mg/day, n = 153; haloperidol 7.5-10 mg/day, n = 151).
      Patients treated with placebo IM were transitioned to oral aripiprazole (analysis
      not included). The primary efficacy measure was mean change in Positive and
      Negative Syndrome Scale-Excited Component (PEC) score from baseline of oral phase
      (last value from 24-hour IM phase) to endpoint (study day 5, last observation
      carried forward). RESULTS: During the oral phase, aripiprazole 15 mg and
      haloperidol 10 mg were both effective in maintaining responses achieved on all
      efficacy measures during the 24-hour IM phase. Mean improvements in PEC scores
      from study day 1 to 5 were -1.37 for aripiprazole and -1.40 for haloperidol (p =
      NS for aripiprazole versus haloperidol). Oral aripiprazole was well tolerated.
      Extrapyramidal symptom-related adverse events were lower for aripiprazole (1.3%)
      than haloperidol (8.0%). Nausea and vomiting occurred more frequently in patients
      receiving aripiprazole (3.9% and 2.6%, respectively) than in those receiving
      haloperidol (0.7% and 1.3%, respectively). CONCLUSIONS: Acutely agitated patients
      with schizophrenia or schizoaffective disorder treated with aripiprazole IM or
      haloperidol IM demonstrated similar effective and safe transition to their
      respective oral formulations. Initial benefits of reduced agitation and improved
      clinical status during the IM phase of the study were maintained throughout the
      oral phase of the study with good tolerability.

PMID- 17522561
TI  - Mania in a case of polypsychopharmacology: pharmacodynamic and pharmacokinetic
      considerations. Do you believe in magic?

PMID- 17522562
TI  - Common problems in psychotherapy training for psychiatry residents.

PMID- 17522563
TI  - Jury bias and psychiatric experts: judges' impressions of international medical
      graduates as expert witnesses.

PMID- 17522564
TI  - The safety and efficacy of ECT and anesthesia in the setting of multiple
      sclerosis.

PMID- 17522565
TI  - Dysphagia: a rare form of dyskinesia?

PMID- 17522566
TI  - When less is more: reducing the incidence of antipsychotic polypharmacy.
AB  - In 2003, the New York State Office of Mental Health initiated a program aimed at
      supporting patient recovery by simplifying antipsychotic regimens. A key
      component of the program, which has been essential in supporting physician
      autonomy, was the introduction of a software program, Psychiatric Clinical
      Knowledge Enhancement System, termed "PSYCKES." This software program enables
      physicians to visualize at a glance the medication history of each of their
      patients as well as of their colleagues' patients, as a way of making better
      informed decisions. The fiscal impact, in the direction of a significant
      reduction in antipsychotic polypharmacy, was not lost on policy-makers, who have
      included $1.3 million in the current state budget for the dissemination of this
      program.

PMID- 17522567
TI  - Treatment of dementia and agitation: a guide for families and caregivers.

PMID- 17522568
TI  - Identifying effective behavioral interventions to prevent STDs: what's next?

PMID- 17522569
TI  - Quantitative detection of Ureaplasma parvum (biovar 1) and Ureaplasma urealyticum
      (biovar 2) in urine specimens from men with and without urethritis by real-time
      polymerase chain reaction.
AB  - BACKGROUND: We previously reported a significant association between Ureaplasma
      urealyticum (biovar 2) and nongonococcal urethritis (NGU). We also found that the
      presence of Ureaplasma parvum (biovar 1) in the male urethra might be the result
      of colonization. OBJECTIVE: The objective of this study was to clarify the
      pathogenic role of human Ureaplasma in NGU by assessing the association of
      bacterial loads with clinical findings and inflammatory responses in the urethra.
      STUDY DESIGN: The 16S rRNA gene of Ureaplasma was quantified by a TaqMan-based
      real-time polymerase chain reaction assay in first-pass urine from 37 men with
      Ureaplasma-positive nonmycoplasmal nonchlamydial NGU (NMNCNGU) and 30 Ureaplasma
      positive men without urethritis. RESULTS: U. urealyticum (biovar 2) loads in 23
      men with NMNCNGU were significantly higher than those in 14 men without
      urethritis. However, U. parvum (biovar 1) loads did not differ significantly
      between 14 men with NMNCNGU and 20 men without urethritis. CONCLUSION: The
      association of increased U. urealyticum (biovar 2) loads with symptomatic
      urethritis suggests that U. urealyticum (biovar 2) may be a pathogen of NGU. Our
      results also suggest that the presence of U. parvum (biovar 1) may not be
      significant in the development of NGU.

PMID- 17522570
TI  - Safety of intravenous nitroglycerin after administration of sildenafil citrate to
      men with coronary artery disease: a double-blind, placebo-controlled, randomized,
      crossover trial.
AB  - OBJECTIVE: Although contraindicated, there are situations when a patient who has
      recently taken a phosphodiesterase 5 inhibitor (e.g., sildenafil) might need
      intravenous nitroglycerin (NTG) treatment. This study determined if, and at what
      dose, intravenous NTG could be administered safely to men with coronary artery
      disease who had recently ingested sildenafil. DESIGN: Double-blind, placebo
      controlled, randomized, crossover trial. SETTING: Four clinical practice sites in
      Canada, Scotland, and the United States. PATIENTS: A total of 34 men (>or=35 yrs)
      with a history of angina pectoris and coronary artery disease (>50% stenosis of
      at least one coronary artery), most of whom were taking antihypertensives.
      INTERVENTIONS: Sildenafil (100 mg) or placebo (single dose; crossover after 3-7
      days) followed 45 mins later by escalating doses of intravenous NTG (160
      microg/min maximum). MEASUREMENTS AND MAIN RESULTS: After sildenafil, there were
      slightly greater maximum (supine) blood pressure decreases and heart rate
      increases (e.g., 4 to 6 mm Hg [systolic] and <or=1 beat/min, at NTG doses of
      <or=80 microg/min) than after placebo. The median maximum tolerated NTG dose
      (range) was 80 (0-160) microg/min for sildenafil vs. 160 (20-160) microg/min for
      placebo (adjusted mean +/- se, 77 +/- 7 vs. 127 +/- 7; p < .0001; analysis of
      variance), and NTG 160 microg/min was tolerated by eight (25%) and 19 (59%) men,
      respectively (p = .0008). Treatment-related adverse events were mostly
      mild/moderate hypotension, headache, and dizziness, which are often associated
      with NTG alone. Sildenafil and metabolite plasma concentrations were lower than
      previously reported in healthy men. CONCLUSIONS: With close monitoring of blood
      pressure and heart rate, men with stable coronary artery disease who have taken
      sildenafil may tolerate intravenous NTG (<or=160 microg/min) with low starting
      dosage and gradual upward titration. The hemodynamic response might be different
      in subgroups not specifically examined in the study (e.g., men presenting with
      acute coronary symptoms). The explanation for the lower than expected plasma
      concentrations remains uncertain.

PMID- 17522571
TI  - Microvascular response to red blood cell transfusion in patients with severe
      sepsis.
AB  - OBJECTIVES: Microvascular alterations may play a role in the development of
      multiple organ failure in severe sepsis. The effects of red blood cell
      transfusions on microvascular perfusion are not well defined. We investigated the
      effects of red blood cell transfusion on sublingual microvascular perfusion in
      patients with sepsis. DESIGN: Prospective, observational study. SETTING: A 31
      bed, medical-surgical intensive care unit of a university hospital. PATIENTS:
      Thirty-five patients with severe sepsis requiring red blood cell transfusions.
      INTERVENTIONS: Transfusion of one to two units of leukocyte-reduced red blood
      cells. MEASUREMENTS AND MAIN RESULTS: The sublingual microcirculation was
      assessed with an Orthogonal Polarization Spectral device before and 1 hr after
      red blood cell transfusion. Red blood cell transfusions increased hemoglobin
      concentration from 7.1 (25th-75th percentile, 6.7-7.6) to 8.1 (7.5-8.6) g/dL (p <
      .01), mean arterial pressure from 75 (69-89) to 82 (75-90) mm Hg (p < .01), and
      oxygen delivery from 349 (278-392) to 391 (273-473) mL/min.M (p < .001).
      Microvascular perfusion was not significantly altered by transfusion, but there
      was considerable interindividual variation. The change in capillary perfusion
      after transfusion correlated with baseline capillary perfusion (Spearman-rho = 
      .49; p = .003). Capillary perfusion was significantly lower at baseline in
      patients who increased their capillary perfusion by >8% compared with those who
      did not (57 [52-64] vs. 75 [70-79]; p < .01), while hemodynamic and global oxygen
      transport variables were similar in the two groups. Red blood cell storage time
      had no influence on the microvascular response to red blood cell transfusion.
      CONCLUSIONS: The sublingual microcirculation is globally unaltered by red blood
      cell transfusion in septic patients; however, it can improve in patients with
      altered capillary perfusion at baseline.

PMID- 17522572
TI  - Altering CO2 during reperfusion of ischemic cardiomyocytes modifies mitochondrial
      oxidant injury.
AB  - OBJECTIVE: Acute changes in tissue CO2 and pH during reperfusion of the ischemic
      heart may affect ischemia/reperfusion injury. We tested whether gradual vs. acute
      decreases in CO2 after cardiomyocyte ischemia affect reperfusion oxidants and
      injury. DESIGN: Comparative laboratory investigation. SETTING: Institutional
      laboratory. SUBJECTS: Embryonic chick cardiomyocytes. INTERVENTIONS: Microscope
      fields of approximately 500 chick cardiomyocytes were monitored throughout 1 hr
      of simulated ischemia (PO2 of 3-5 torr, PCO2 of 144 torr, pH 6.8), followed by 3
      hrs of reperfusion (PO2 of 149 torr, PCO2 of 36 torr, pH 7.4), and compared with
      cells reperfused with relative hypercarbia (PCO2 of 71 torr, pH 6.8) or
      hypocarbia (PCO2 of 7 torr, pH 7.9). MEASUREMENTS AND MAIN RESULTS: The measured
      outcomes included cell viability (via propidium iodide) and oxidant generation
      (reactive oxygen species via 2',7'-dichlorofluorescin oxidation and nitric oxide
      [NO] via 4,5-diaminofluorescein diacetate oxidation). Compared with normocarbic
      reperfusion, hypercarbia significantly reduced cell death from 54.8% +/- 4.0% to
      26.3% +/- 2.8% (p < .001), significantly decreased reperfusion reactive oxygen
      species (p < .05), and increased NO at a later phase of reperfusion (p < .01).
      The NO synthase inhibitor N-nitro-L-arginine methyl ester (200 microM) reversed
      this oxidant attenuation (p < .05), NO increase (p < .05), and the
      cardioprotection conferred by hypercarbic reperfusion (increasing death to 54.3%
      +/- 6.0% [p < .05]). Conversely, hypocarbic reperfusion increased cell death to
      80.4% +/- 4.5% (p < .01). It also increased reactive oxygen species by almost two
      fold (p = .052), without affecting the NO level thereafter. Increased reactive
      oxygen species was attenuated by the mitochondrial complex III inhibitor
      stigmatellin (20 nM) when given at reperfusion (p < .05). Cell death also
      decreased from 85.9% +/- 4.5% to 52.2% +/- 6.5% (p < .01). The nicotinamide
      adenine dinucleotide phosphate oxidase inhibitor apocynin (300 microM) had no
      effect on reperfusion reactive oxygen species. CONCLUSIONS: Altering CO2 content
      during reperfusion can significantly affect myocardial postresuscitation injury,
      in part by modifying mitochondrial oxidants and NO synthase-induced NO
      production.

PMID- 17522573
TI  - Effects of a catecholamine-induced increase in cardiac output on lung injury
      after experimental unilateral pulmonary acid instillation.
AB  - OBJECTIVES: Increasing pulmonary blood flow aggravated ventilation-associated
      lung injury in ex vivo animal experiments, but data were less consistent in an in
      vivo animal model and do not reflect redistributed lung perfusion seen in
      clinical acute lung injury. We sought to determine the effects of increased
      cardiac output on markers of lung injury in an in vivo model of inhomogeneous
      lung perfusion and injury. DESIGN: Prospective, controlled animal study. SETTING:
      Experimental research laboratory of a university hospital. SUBJECTS: A total of
      50 anesthetized, mechanically ventilated, male Wistar rats. INTERVENTIONS:
      Unilateral lung injury was induced in rats by left lung acid instillation. After
      24 hrs, animals were anesthetized and subjected to mechanical ventilation (tidal
      volume, 8 mL/kg; positive end-expiratory pressure, 7 cm H2O; FIO2, 0.4) and
      continuous infusion of either 10 microg x kg x min dobutamine or isotonic saline
      (control) for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Cardiac output and
      differential lung perfusion were recorded throughout the ventilation period.
      Right and left lung wet-to-dry weight ratio, cytokines and inflammatory cells in
      lung lavage, and histologic lung injury were measured postmortem. After acid
      injury, lung perfusion was preferentially distributed to the noninjured lung.
      Dobutamine increased baseline cardiac output (>70%) and perfusion of both lungs
      (left, acid-instilled lung: from 16 +/- 2 to 29 +/- 6 mL/min; right, non-acid
      instilled lung: from 54 +/- 3 to 98 +/- 7 mL/min). There was no difference in
      left lung injury between dobutamine- and saline-infused animals, but right lung
      injury was aggravated in dobutamine-infused animals, as indicated by increased
      lung edema, histologic lung injury, and cell counts in lavage. CONCLUSIONS: In
      the setting of unilateral lung injury and uneven lung perfusion, a dobutamine
      induced increase in cardiac output has potentially detrimental effects on the
      opposite lung.

PMID- 17522574
TI  - Role of platelet-activating factor in pneumolysin-induced acute lung injury.
AB  - OBJECTIVE: Acute respiratory failure is a major complication of severe
      pneumococcal pneumonia, characterized by impairment of pulmonary microvascular
      barrier function and pulmonary hypertension. Both features can be evoked by
      pneumolysin (PLY), an important virulence factor of Streptococcus pneumoniae. We
      hypothesized that platelet-activating factor (PAF) and associated downstream
      signaling pathways play a role in the PLY-induced development of acute lung
      injury. DESIGN: Controlled, ex vivo laboratory study. SUBJECTS: Female Balb/C
      mice, 8-12 wks old. INTERVENTIONS: Ventilated and blood-free-perfused lungs of
      wild-type and PAF receptor-deficient mice were challenged with recombinant PLY.
      MEASUREMENTS AND MAIN RESULTS: Intravascular PLY, but not the pneumolysoid Pd-B
      (PLY with a Trp-Phe substitution at position 433), caused an impressive dose
      dependent increase in pulmonary vascular resistance and increased PAF in lung
      homogenates, as detected by reversed-phase high-performance liquid chromatography
      coupled to tandem mass spectrometry. The pressor response was reduced in lungs of
      PAF receptor-deficient mice and after PAF receptor blockade by BN 50730. PLY and
      exogenous PAF increased thromboxane B2 in lung effluate, and thromboxane receptor
      inhibition by BM 13505 diminished the pressor response to PLY. Differential
      inhibition of intracellular signaling steps suggested significant contribution of
      phosphatidylcholine-specific phospholipase C and protein kinase C and of the
      Rho/Rho-kinase pathway to PLY-induced pulmonary vasoconstriction. Unrelated to
      the pulmonary arterial pressor response, microvascular leakage of PLY was
      diminished in lungs of PAF receptor-deficient mice as well. CONCLUSIONS: PAF
      significantly contributed to PLY-induced acute injury in murine lungs. The PAF
      mediated pressor response to PLY depends on thromboxane and on the downstream
      effectors phosphatidylcholine-specific phospholipase C, protein kinase C, and Rho
      kinase.

PMID- 17522575
TI  - Caring for a major government official: challenges and lessons learned.
AB  - OBJECTIVE: Analysis of the medical, organizational, and administrative issues
      surrounding the care of a dignitary in an intensive care unit. THE STORY: On
      January 4, 2006, Ariel Sharon, the Israeli Prime Minister was emergently admitted
      to the Hadassah-Hebrew University Medical Center in Jerusalem owing to a severe
      intracranial hemorrhage. Immediately following his admission, he underwent an
      extensive neurosurgical procedure to control the bleeding. Thereafter, he
      required intensive care for 5 months and underwent additional procedures. This
      admission presented organizational and administrative challenges. ORGANIZATION OF
      MEDICAL CARE: The major challenge was to provide the Prime Minister with the best
      medical care while avoiding the "very important person syndrome" and
      simultaneously continuing routine hospital activities. To coordinate his
      complicated medical management, a consultation forum was established composed of
      all the physicians directly involved in Mr. Sharon's care. Additionally, a senior
      intensivist was chosen to coordinate the medical care and, along with a physician
      from the hospital administration, assist with administrative issues.
      ADMINISTRATIVE ASPECTS: Among the issues that the coordinating team addressed,
      with the help of many other hospital services, included patient confidentiality
      vs. public information, security of the patient's medical chart (including
      laboratory data and imaging), and coordination with security personnel.
      CONCLUSION: The acute care of a major governmental official requires the medical
      staff to address many administrative issues, while providing the "very important
      person" patient with appropriate intensive medical care. This article presents a
      strategy for addressing these issues.

PMID- 17522576
TI  - A protocol for high-frequency oscillatory ventilation in adults: results from a
      roundtable discussion.
AB  - OBJECTIVE: Ventilator settings typically used for high-frequency oscillatory
      ventilation (HFO) in adults provide acceptable gas exchange but may not take best
      advantage of its lung-protective aspects. We provide guidelines for HFO in adults
      with acute respiratory distress syndrome that should optimize the lung-protective
      characteristics of this ventilation mode. DESIGN: Roundtable discussions,
      iterative revisions, and consensus. SETTING: Five academic medical centers.
      PATIENTS: Not applicable. INTERVENTIONS: Participants addressed how to best
      maintain ventilation through combinations of oscillation pressure amplitude,
      frequency, and the use of an endotracheal tube cuff leak, and to maintain
      oxygenation through combinations of recruitment maneuvers, mean airway pressure,
      and oxygen concentration. The guiding principles were to provide lung protective
      ventilation by minimizing the size of tidal volumes, and balance the risks and
      benefits of lung recruitment and distension. MAIN RESULTS: HFO may provide
      smaller tidal volumes and more complete lung recruitment than conventional modes.
      To optimize these features, we recommend use of the maximum pressure-oscillation
      amplitude coupled with the highest tolerated frequency, targeting a pH of only
      7.25-7.35. This will yield a smaller tidal volume than typical HFO settings where
      frequency is limited to 6 Hz or less and pressure amplitude is submaximal. Lung
      recruitment can be achieved with the use of recruitment maneuvers, especially
      during the first several days of HFO. Recruitment may be augmented or sustained
      with generous mean airway pressures. These may either be chosen from a table of
      recommended mean airway pressure and oxygen concentration combinations, or
      individually titrated based on the oxygenation response of each patient.
      CONCLUSIONS: Modification of the goals and tactics of HFO use may better protect
      against ventilator-associated lung injury. Further clinical trials are needed to
      compare the effects on patient outcome of the best use of HFO compared to the
      most protective use of conventional modes in adult acute respiratory distress
      syndrome.

PMID- 17522577
TI  - Fresh frozen plasma transfusion in critically ill patients.
AB  - OBJECTIVES: Although guidelines for fresh frozen plasma (FFP) use have been
      published, many transfusions are considered inappropriate. Current guidelines
      suggest few circumstances in which FFP transfusion to critically ill patients is
      warranted. The objectives of this study were to evaluate the consistency of
      Canadian guidelines for FFP administration to critically ill patients and to
      examine factors associated with inappropriate FFP transfusions. DESIGN:
      Retrospective cohort study. SETTING: 15-bed medical surgical intensive care unit
      in a teaching hospital. PATIENTS: 254 consecutive adults admitted during 1 yr
      expected to stay in intensive care for more than 72 hrs. INTERVENTION: None.
      MEASUREMENTS AND MAIN RESULTS: Patient demographics, illness severity, life
      support, intensive care and hospital length of stay, and survival were
      prospectively collected. All FFP orders were identified from the hospital
      laboratory information system. For each order, coagulation parameters, planned
      invasive interventions, recent or current bleeding, and bleeding severity were
      retrospectively collected. Three observers independently adjudicated whether
      transfusions were consistent with guidelines, inconsistent but appropriate for
      the intensive care context, or inappropriate. Of 254 patients, 76 (29.9%)
      received FFP, accounting for 225 orders to transfuse 547 units. Of 225 orders, 73
      (32.4%) were consistent with guidelines, 45 (20.0%) were inconsistent but
      appropriate, and 107 (47.6%) were inappropriate. Considering transfusions
      clustered within patients, chance-independent agreement on whether transfusions
      were inappropriate or not was high (phi 0.73, 0.64-0.81). Independent
      determinants of inappropriate FFP were the presence of less severe coagulopathy
      as indicated by lower international normalized ratios (p < .0001) and the absence
      of bleeding (p < .0001) of planned invasive procedure (p = .0001). CONCLUSIONS:
      Critically ill patients frequently receive inappropriate FFP transfusions. Many
      transfusions may be appropriate for the intensive care setting, although they are
      inconsistent with expert recommendations, highlighting that further studies are
      needed to assess the effectiveness and safety of FFP transfusion in critical
      illness.

PMID- 17522578
TI  - The Pancreatitis Outcome Prediction (POP) Score: a new prognostic index for
      patients with severe acute pancreatitis.
AB  - OBJECTIVE: Severe acute pancreatitis, defined as pancreatitis with distant organ
      dysfunction, is a condition carrying a high mortality and morbidity. Current
      outcome prediction scores are based on small populations, usually from single
      specialist centers. Some scores cannot be applied until several days into
      hospital admission. We thus sought to develop a new and more sensitive outcome
      prediction score--the Pancreatitis Outcome Prediction (POP) Score--for these high
      risk patients. DESIGN: Retrospective cohort study of a large multicenter
      intensive care database. SETTING: One hundred fifty-nine U.K. intensive care
      units. PATIENTS: Participants were 2,462 patients admitted to intensive care
      units with severe acute pancreatitis. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Demographic, physiologic, and biochemical data collected within the
      first 24 hrs of intensive care unit admission were used to develop a risk
      prediction score using logistic regression. The six variables with the strongest
      relationship to hospital outcome--arterial pH, age, serum urea, mean arterial
      pressure, PaO2/FIO2 ratio, and total serum calcium (in order of decreasing
      impact)--produced a model with a prognostic discrimination (area under the
      receiver operating characteristic curve = 0.838) superior to other models. These
      six factors were used to develop an objectively weighted multivariate prognostic
      score ranging from 0 to 40 points. CONCLUSIONS: Prognostic stratification of
      patients with severe acute pancreatitis requiring intensive care offers a useful
      audit tool to gauge unit performance and improve delineation of subsets for
      prospective trials. Prospective validation of this new outcome prediction score
      is required, preferably in different countries. The validity of the POP Score for
      either hospital or intensive care admission could also be tested and assessed for
      superiority over existing scores.

PMID- 17522579
TI  - Increased circulating endothelial progenitor cells in septic patients:
      correlation with survival.
AB  - OBJECTIVE: Endothelial damage and detachment of endothelial cells are known to
      occur in septic patients. Thus, recruitment of circulating endothelial progenitor
      cells (cEPCs) to these lesions might have a beneficial effect on the clinical
      course in septic patients. Therefore, we were interested in whether EPCs,
      detected by flow cytometry, are increasingly mobilized during sepsis and if this
      mobilization is associated with clinical outcome. DESIGN: Prospective,
      nonrandomized study. SETTING: Intensive care unit of a university hospital.
      PATIENTS: Patients with (n = 32) and without (n = 15) sepsis and healthy
      volunteers (n = 15). INTERVENTIONS: Peripheral blood mononuclear cells were
      isolated by Ficoll density gradient centrifugation, and cEPCs were characterized
      by three-color fluorescence flow cytometry using antibodies against CD133, CD34,
      and vascular endothelial growth factor receptor-2. Serum concentrations of
      vascular endothelial growth factor, granulocyte macrophage-colony stimulating
      factor, and erythropoietin were determined by enzyme-linked immunosorbent assay.
      Severity of sepsis was assessed according to Acute Physiology and Chronic Health
      Evaluation II scoring. MEASUREMENTS AND MAIN RESULTS: In septic patients, the
      number of cEPCs was significantly higher than in nonseptic intensive care unit
      patients (p < .05) and healthy controls (p < .02). Nonsurvivors (n = 8), defined
      as death within 28 days after onset of sepsis, had significantly lower numbers of
      cEPCs than survivors (n = 24) (p < .0001). The number of cEPCs was correlated
      with survival in septic patients. Serum vascular endothelial growth factor
      concentrations were significantly higher in septic patients compared with
      nonseptic intensive care unit patients and healthy controls (p < .01) and
      correlated with the cEPC numbers (p < .0001). Similar findings were observed for
      granulocyte macrophage-colony stimulating factor and erythropoietin. CONCLUSIONS:
      Our data suggest that cEPC enumeration in peripheral blood of septic patients
      might be a valuable marker to assess the clinical outcome in these patients.

PMID- 17522580
TI  - Comparative effects of early versus delayed use of norepinephrine in resuscitated
      endotoxic shock.
AB  - OBJECTIVE: To assess hemodynamic, tissue oxygenation, and tissue perfusion
      changes by comparing traditional therapy (fluid resuscitation followed by
      vasopressor treatment) and alternative therapy (early vasopressor treatment) in a
      hyperkinetic and sedated model of endotoxic shock. DESIGN: Prospective controlled
      experimental study. SETTING: Animal research laboratory. SUBJECTS: Male Wistar
      rats. INTERVENTIONS: Rats were anesthetized, mechanically ventilated, paralyzed,
      and instrumented to measure mean arterial pressure, heart rate, pulse pressure
      variation, aortic and mesenteric blood flow, muscle and liver tissue oxygen
      pressure, blood gas, and lactate. Rats were randomly divided into five groups (n
      = 7): endotoxin alone (Endo), endotoxin plus norepinephrine (Endo/NE), endotoxin
      plus fluid therapy alone (ENDO/Fl), endotoxin plus fluid therapy plus late
      catecholamine (Endo/Fl/Late NE), and endotoxin plus fluid therapy plus
      simultaneous norepinephrine administration (Endo/Fl/Early NE). MEASUREMENTS AND
      MAIN RESULTS: Mean arterial pressure increased to baseline values only in the
      catecholamine-treated group (p < .05). In ENDO/Fl, Endo/Fl/Late NE, and
      Endo/Fl/Early NE, aortic blood flow was maintained. Mesenteric blood flow was
      maintained at baseline values only in the catecholamine-treated groups.
      Mesenteric/aortic blood flow ratio was higher in the early catecholamine group (p
      < .05). Endo and ENDO/Fl were associated with a marked decrease in liver PO2,
      which was maintained in catecholamine-treated groups (p < .01). Plasma lactate
      was lower in the Endo/Fl/Early NE group. Volume resuscitation was higher in Endo
      and Endo/Fl/Late NE groups with 28 +/- 6 and 27 +/- 4 mL, respectively, when
      compared with the Endo/Fl/Early NE group (19 +/- 3 mL) (p < .05). CONCLUSIONS:
      The use of norepinephrine was associated with improved mean arterial pressure,
      sustained aortic and mesenteric blood flow, and better tissue oxygenation when
      compared with fluid resuscitation alone, irrespective of time of administration.
      The early use of norepinephrine plus volume expansion was associated with a
      higher proportion of blood flow redistributed to the mesenteric area, lower
      lactate levels, and less infused volume. Thus, the early use of norepinephrine is
      safe and may decrease the need for volume resuscitation.

PMID- 17522581
TI  - Biologically variable ventilation improves gas exchange and respiratory mechanics
      in a model of severe bronchospasm.
AB  - OBJECTIVE: Mechanical ventilation can be lifesaving for status asthmaticus, but
      how best to accomplish mechanical ventilation is unclear. Biologically variable
      ventilation (mechanical ventilation that emulates healthy variation) and
      conventional control mode ventilation (monotonously regular) were compared in an
      animal model of bronchospasm to determine which approach yields better gas
      exchange and respiratory mechanics. DESIGN: A randomized prospective trial of
      biologically variable ventilation vs. control mode ventilation in swine. SETTING:
      University research laboratory. SUBJECTS: Eighteen farm-raised pigs.
      INTERVENTIONS: Methacholine was administered as a nebulized aerosol to initiate
      bronchospasm, defined as doubling of peak inspiratory pressure and respiratory
      system resistance, and then randomized (n = 9 each group) to either continue
      control mode ventilation or switch to biologically variable ventilation at the
      same minute ventilation. Over the next 4 hrs, hemodynamics, blood gases,
      respiratory mechanics, and carbon dioxide expirograms were recorded hourly. At
      end-experiment, tracheobronchial lavage was undertaken to determine interleukin-6
      and -10 concentrations. MEASUREMENTS AND MAIN RESULTS: Measurements of
      physiologic variables and inflammatory cytokines showed that biologically
      variable ventilation significantly improved gas exchange, with greater arterial
      oxygen tensions (p = .006; group x time interaction), lower arterial carbon
      dioxide tensions (p = .0003; group effect), lower peak inspiratory pressures (p =
      .0001; group x time), greater static compliance (p = .0001; group x time),
      greater dynamic compliance (p = .0001; group x time), and lower total respiratory
      system resistance (p = .028; group x time), compared with conventional
      ventilation. The appearance of inflammatory cytokines in bronchoalveolar lavage
      fluid (interleukin-6 and -10) was not affected by mode of ventilation.
      CONCLUSIONS: In this experimental model, biologically variable ventilation was
      superior to control mode ventilation in terms of gas exchange and respiratory
      mechanics during severe bronchospasm.

PMID- 17522582
TI  - Knowledge translation in critical care: factors associated with prescription of
      commonly recommended best practices for critically ill patients.
AB  - OBJECTIVE: To describe prescription rates of commonly recommended best practices
      (clinical interventions with a strong base of evidence supporting their
      implementation) for critically ill patients and determine factors associated with
      increased rates of prescription. DESIGN: A retrospective observational study.
      SETTING: A university-affiliated medical-surgical-trauma intensive care unit over
      a 1-yr period. PATIENTS: One hundred randomly selected critically ill patients.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the best practices
      studied, there was great variability in the proportion of patients eligible
      (median 36.5%, range 10% to 100%) and the proportion without contraindication
      (32.5%, range 10% to 86%) for each practice. The median rate of prescription of
      best practices for eligible patients was 56.5%, with a range from 8% to 95%.
      There was greater prescription of best practices when standard admission orders
      included an option to prescribe them (p = .048). Among those practices with
      standard admission orders, there was greatest prescription for practices
      additionally having a specialty consultation service (p = .004). There was an
      inverse association between severity of illness and prescription of best
      practices (p = .001): Sicker patients were less likely to be prescribed best
      practices. CONCLUSIONS: There may be substantial variability in the acceptance
      and prescription of commonly recommended best practices for critically ill
      patients. Standard order sets and focused specialty consultation may improve
      knowledge translation and prescription of best practice.

PMID- 17522583
TI  - Transfusion from male-only versus female donors in critically ill recipients of
      high plasma volume components.
AB  - OBJECTIVE: To reduce the incidence of transfusion-related acute lung injury
      (ALI), the American Association of Blood Banks recently recommended rapid
      implementation of strategies to minimize transfusion of high plasma volume
      components, fresh frozen plasma and apheresis platelets, from potentially
      alloimmunized donors, especially females. The objective of this study was to
      evaluate the effect of transfusing components from male-only vs. female donors on
      development of ALI, gas exchange, and outcome in critically ill patients. DESIGN:
      In this retrospective case-control study, we identified patients who received
      high plasma volume components from male-only donors and compared them with
      patients matched by severity of illness, postoperative state, and number of
      transfusions but who received high plasma volume components from female donors.
      SETTING: Four intensive care units at a tertiary medical center. PATIENTS:
      Critically ill patients who received >2 units of fresh frozen plasma or apheresis
      platelets. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From a database of
      3,567 patients who received a total of 46,101 units of fresh frozen plasma and
      6,251 units of apheresis platelets, we identified 112 patients who received three
      or more male-only donor components and 112 matched controls. Baseline
      characteristics, ALI risk factors, and development of ALI were similar between
      the two groups. Arterial oxygenation (PaO2/FIO2) worsened after the female (mean
      difference -52, 95% confidence interval -14 to -91, p = .008) but not after male
      only donor product transfusion (mean difference 22, 95% confidence interval -23
      to 67, p = .325). Male-only component recipients had more ventilator-free days
      (median 28 vs. 27, p = .006) and a trend toward lower hospital mortality rates
      (14% vs. 24%, p = .054). CONCLUSIONS: In critically ill recipients of high plasma
      volume components, gas exchange worsened significantly after transfusion of
      female but not male donor components. Prospective studies are needed to evaluate
      the effect of recommendations by the American Association of Blood Banks on
      outcome of transfused critically ill patients.

PMID- 17522584
TI  - The fibrin-derived peptide Bbeta15-42 is cardioprotective in a pig model of
      myocardial ischemia-reperfusion injury.
AB  - OBJECTIVE: The fibrin-derived peptide Bbeta15-42 has been shown to reduce infarct
      size in rodent models of ischemia-reperfusion injury. To increase its potential
      for translation into the clinic, we studied the effects of Bbeta15-42 in pigs,
      whose coronary anatomy is similar to that of humans. In addition, we evaluated
      the pharmacokinetics and safety of Bbeta15-42 in several species, including
      humans. DESIGN: Animal study and phase I trial. SETTING: University hospital and
      contract research laboratories. SUBJECTS: Pigs/healthy volunteers. INTERVENTIONS:
      Male farm-bred Landrace pigs were subjected to 1 hr of left anterior descending
      coronary artery occlusion followed by 3 hrs of reperfusion. At the time of
      reperfusion, Bbeta15-42 (2.4 mg/kg, n = 6) or random peptide (control; 2.4 mg/kg,
      n = 6) was administered as an intravenous bolus. As a positive control, pigs were
      subjected to ischemic preconditioning (n = 6). Cardiac damage and hemodynamics
      were recorded. Biodistribution and pharmacokinetics of Bbeta15-42 were determined
      in rats and dogs. In a phase I trial involving 30 male healthy volunteers,
      pharmacokinetics and safety were tested in a randomized, double-blinded, placebo
      controlled, parallel-group, single ascending dose study. MEASUREMENTS AND MAIN
      RESULTS: Bbeta15-42 and ischemic preconditioning significantly reduced myocardial
      infarct size and troponin I levels. Bbeta15-42 also reduces interleukin-6 levels,
      underlining its anti-inflammatory properties. Furthermore, in humans, the
      pharmacokinetics of the peptide Bbeta15-42 were comparable to those of animals,
      and no serious adverse effects were observed. CONCLUSIONS: Bbeta15-42 elicits
      cardioprotection in pigs and is clinically safe in phase I testing of humans.
      This study confirms the new concept of a pathogenic role of fibrin derivatives in
      myocardial reperfusion injury, which can be inhibited by peptide Bbeta15-42.

PMID- 17522585
TI  - Recombinant activated factor VII for refractory bleeding after acute aortic
      dissection surgery: a propensity score analysis.
AB  - OBJECTIVE: The aim of this study was to assess safety and effectiveness of
      recombinant activated factor VII (rFVIIa) in patients with refractory bleeding
      undergoing acute aortic dissection surgery with deep hypothermic circulatory
      arrest. DESIGN: Propensity score-matched analysis. SETTING: University hospital.
      PATIENTS: Twenty-three cardiac surgery patients receiving rFVIIa compared with 23
      matched controls. INTERVENTIONS: An intravenous bolus of rFVIIa (70 microg/kg)
      was administered at the end of a complete transfusion protocol. Five patients
      received rFVIIa in the operating room, and 18 patients received rFVIIa in the
      intensive care unit. Four of the intensive care unit patients required a second
      dose. MEASUREMENTS AND MAIN RESULTS: Blood loss and transfusion requirements were
      significantly reduced in the period after rFVIIa administration. A highly
      significant reduction in hourly blood loss was found at -1 hr vs. 0 hrs and 0 hrs
      vs. 1 hr (-194 and -77.5 mL, respectively; both adjusted p < .001). In addition,
      significant improvements of international normalized ratio (p < .001), partial
      thromboplastin time (p < .001), platelet count (p < .001), fibrinogen (p < .001),
      and antithrombin (p < .001) were detected after rFVIIa administration. The two
      groups did not differ regarding adverse events. CONCLUSIONS: rFVIIa was
      successfully used as an additional therapy both during and after acute aortic
      dissection surgery with deep hypothermic circulatory arrest, when bleeding was
      refractory to conventional methods. Randomized studies are necessary to confirm
      the safety and efficacy of rFVIIa in this setting.

PMID- 17522586
TI  - Natural history of asymptomatic bacterial vaginosis in a high-risk group of
      women.

PMID- 17522587
TI  - Exposure to secondhand smoke among students aged 13-15 years--worldwide, 2000
      2007.
AB  - Breathing secondhand smoke (SHS) causes heart disease and lung cancer in adults
      and increased risks for sudden infant death syndrome, acute respiratory
      infections, middle-ear disease, worsened asthma, respiratory symptoms, and slowed
      lung growth in children. No risk-free level of exposure to SHS exists. The Global
      Youth Tobacco Survey (GYTS), initiated in 1999 by the World Health Organization
      (WHO), the Canadian Public Health Association, and CDC includes questions related
      to tobacco use, including exposure to SHS. This report examines data collected
      from 137 jurisdictions (i.e., countries and territories) during 2000-2007,
      presents estimates of exposure to SHS at home and in places other than the home
      among students aged 13-15 years who had never smoked, and examines the
      association between exposure to SHS and susceptibility to initiating smoking.
      GYTS data indicated that nearly half of never smokers were exposed to SHS at home
      (46.8%), and a similar percentage were exposed in places other than the home
      (47.8%). Never smokers exposed to SHS at home were 1.4-2.1 times more likely to
      be susceptible to initiating smoking than those not exposed. Students exposed to
      SHS in places other than the home were 1.3-1.8 times more likely to be
      susceptible to initiating smoking than those not exposed. As part of their
      comprehensive tobacco-control programs, countries should take measures to create
      smoke-free environments in all indoor public places and workplaces.

PMID- 17522588
TI  - State-specific prevalence of smoke-free home rules--United States, 1992-2003.
AB  - Secondhand smoke (SHS) causes premature death and disease in children and
      nonsmoking adults. The home is the primary source of exposure to SHS for infants
      and children and a major source of SHS exposure for nonsmoking adults. To assess
      trends in national and state-specific prevalence of home "no smoking" rules
      (i.e., smoke-free home rules), CDC analyzed data from the Tobacco Use Supplement
      to the Current Population Survey for 1992-1993, 1998-1999, and 2003. This report
      summarizes the results of that analysis, which indicated that the national
      prevalence of households with smoke-free home rules in the United States
      increased significantly, from 43.2% during 1992-1993 to 72.2% in 2003. During
      this period, the national prevalence of such rules increased from 9.6% to 31.8%
      among households with at least one smoker and from 56.8% to 83.5% among
      households with no smoker. A regression analysis of the rate of change over time
      indicated that the increase in smoke-free homes during this period was not
      significantly different for households with at least one smoker compared with
      households with no smoker. Statistically significant increases in the prevalence
      of smoke-free home rules were also observed in all states, although variation was
      observed among states. Comprehensive tobacco-control measures, including 1)
      evidence-based interventions to help smokers quit, 2) policies making workplaces
      and public places smoke-free, 3) voluntary rules making homes smoke-free, and 4)
      initiatives to educate the public regarding the health effects of SHS, are needed
      to further reduce exposure of nonsmokers to SHS.

PMID- 17522589
TI  - Outpatient rehabilitation among stroke survivors--21 States and the District of
      Columbia, 2005.
AB  - Stroke is a leading cause of severe and long-term disability in the United
      States. Approximately 700,000 persons in the United States have a new or
      recurrent stroke each year; among those who survive, only 10% recover completely,
      and many of the remaining survivors need rehabilitation because of resulting
      impairments. Long-term disability not only affects functional status and social
      roles among stroke survivors but also results in substantial costs; the combined
      direct and indirect costs of stroke are projected to be $62.7 billion in the
      United States in 2007. Although studies have established that timely and
      intensive rehabilitation can substantially improve patients' functional outcomes
      and quality of life after an acute stroke, few studies have provided population
      based estimates of the prevalence of acute stroke rehabilitation. To examine the
      prevalence of outpatient stroke rehabilitation among selected populations, CDC
      assessed data from the 2005 Behavioral Risk Factor Surveillance System (BRFSS)
      survey on stroke survivors in 21 states and the District of Columbia (DC). This
      report summarizes the results of that assessment, which indicated that 30.7% of
      the stroke survivors received outpatient rehabilitation and a higher prevalence
      of outpatient stroke rehabilitation was reported among men, non-Hispanic blacks,
      unemployed or retired adults, and persons living in the center city of a
      metropolitan statistical area (MSA) than in comparison groups. The findings
      indicated that the prevalence of stroke survivors who were receiving outpatient
      stroke rehabilitation services was lower than would be expected if clinical
      practice guideline recommendations for all stroke patients had been followed.
      Increasing the number of stroke survivors who receive needed outpatient
      rehabilitation might lead to better functional status and quality of life in this
      population.

PMID- 17522590
TI  - Stressing the role of FoxO proteins in lifespan and disease.
AB  - Members of the class O of forkhead box transcription factors (FoxO) have
      important roles in metabolism, cellular proliferation, stress tolerance and
      probably lifespan. The activity of FoxOs is tightly regulated by post
      translational modifications, including phosphorylation, acetylation and
      ubiquitylation. Several of the enzymes that regulate the turnover of these post
      translational modifications are shared between FoxO and p53. These regulatory
      enzymes affect FoxO and p53 function in an opposite manner. This shared yet
      opposing regulatory network between FoxOs and p53 may underlie a 'trade-off'
      between disease and lifespan.

PMID- 17522591
TI  - Molecular regulation of angiogenesis and lymphangiogenesis.
AB  - Blood vessels and lymphatic vessels form extensive networks that are essential
      for the transport of fluids, gases, macromolecules and cells within the large and
      complex bodies of vertebrates. Both of these vascular structures are lined with
      endothelial cells that integrate functionally into different organs, acquire
      tissue-specific specialization and retain plasticity; thereby, they permit growth
      during tissue repair or in disease settings. The angiogenic growth of blood
      vessels and lymphatic vessels coordinates several biological processes such as
      cell proliferation, guided migration, differentiation and cell-cell
      communication.

PMID- 17522592
TI  - Unravelling developmental dynamics: transient intervention and live imaging in
      plants.
AB  - Plant development is dynamic in nature. This is exemplified in developmental
      patterning, in which roots and shoots rapidly elongate while simultaneously
      giving rise to precisely positioned new organs over a time course of minutes to
      hours. In this Review, we emphasize the insights gained from simultaneous use of
      live imaging and transient perturbation technologies to capture the dynamic
      properties of plant processes.

PMID- 17522593
TI  - Embryonic stem-cell culture as a tool for developmental cell biology.
AB  - The cell biology of the early processes of mammalian embryogenesis, such as germ
      layer formation, has been technically challenging to study owing to the size and
      accessibility of mammalian embryos. Embryonic stem cells, which can generate the
      three germ layers in vitro, are useful for studying embryogenesis at the cellular
      level. So, how can the study of embryonic stem cells and their differentiation
      provide a deeper understanding of the cell biology of early development?

PMID- 17522594
TI  - The bradykinin type 2 receptor BE1 polymorphism and ethnicity influence systolic
      blood pressure and vascular resistance.
AB  - We examined the effect of -58 C/T and BE1 +9/-9 polymorphisms in the bradykinin
      B2 receptor gene on forearm vascular resistance (FVR) before and during
      intrabrachial artery infusion of the B2 receptor-, endothelium-dependent agonist
      bradykinin and the endothelium-independent agonist sodium nitroprusside in 228
      normotensive subjects. In 166 white Americans, systolic blood pressure (SBP) and
      pulse pressure were highest in the BE1 +9/+9 group (118+/-2 and 51+/-2 mm Hg,
      respectively; P<0.05 versus -9/-9 for either), intermediate in the +9/-9 group
      (114+/-1 and 49+/-1 mm Hg, P<0.05 versus -9/-9 for pulse pressure), and lowest in
      the -9/-9 group (110+/-2 and 44+/-2 mm Hg). In 62 black Americans, FVR was 25%
      higher in the BE1 +9/+9 group compared with the BE1 +9/-9 and -9/-9 groups at
      baseline (P=0.038) or during bradykinin (P=0.03). Increased SBP or vascular
      resistance may contribute to increased left ventricular mass reported previously
      in individuals with the BE1+9/+9 genotype.

PMID- 17522595
TI  - Identification of novel CYP2A6*1B variants: the CYP2A6*1B allele is associated
      with faster in vivo nicotine metabolism.
AB  - Cytochrome P450 2A6 (CYP2A6) is the human enzyme responsible for the majority of
      nicotine's metabolism. CYP2A6 genetic variants contribute to the interindividual
      and interethnic variation in nicotine metabolism. We examined the association
      between the CYP2A6*1B variant and nicotine's in vivo metabolism. Intravenous
      infusions of deuterium-labeled nicotine were administered to 292 volunteers, 163
      of whom were White and did not have common CYP2A6 variants, other than CYP2A6*1B.
      We discovered three novel CYP2A6*1B variants in the 3'-flanking region of the
      gene that can confound genotyping assays. We found significant differences
      between CYP2A6*1A/*1A, CYP2A6*1A/*1B, and CYP2A6*1B/*1B groups in total nicotine
      clearance (17.2+/-5.2, 19.0+/-6.4, and 20.4+/-5.9, P<0.02), non-renal nicotine
      clearance (16.4+/-5.0, 18.5+/-6.2, and 19.8+/-5.7, P<0.01), and the plasma trans
      3'-hydroxycotinine/cotinine ratio (0.26+/-0.1, 0.26+/-0.1, and 0.34+/-0.1,
      P<0.001). There were also differences in total nicotine (29.4+/-12.9, 25.8+/
      0.12.9, and 22.4+/-12.4, P<0.01), cotinine (29.2+/-8.1, 32.2+/-9.1, and 33.0+/
      6.6, P<0.01) and trans-3'-hydroxycotinine (32.4+/-9.1, 34.2+/-12.3, and 41.3+/
      11.3, P<0.001) excreted in the urine. We report evidence that CYP2A6*1B genotype
      is associated with faster nicotine clearance in vivo, which will be important to
      future CYP2A6 genotype association studies.

PMID- 17522596
TI  - Pharmacokinetics and pharmacodynamics of the novel daily rivastigmine transdermal
      patch compared with twice-daily capsules in Alzheimer's disease patients.
AB  - A transdermal patch has been developed for the cholinesterase inhibitor
      rivastigmine. This study investigated the pharmacokinetics and pharmacodynamics
      of rivastigmine and NAP226-90, and compared drug exposure between patch and
      capsule administrations. This was an open-label, parallel-group study in
      Alzheimer's disease patients randomized to receive either capsule (1.5-6 mg Q12H,
      i.e., 3-12 mg/day) or patch (5-20 cm2) in ascending doses through four 14-day
      periods. The patch showed lower Cmax (ca. 30% lower at 20 cm2, 19.5 versus 29.3
      ng/ml), longer tmax (8.0 versus 1.0 h), and greater AUC (ca. 1.8-fold at 20 cm2,
      345 versus 191 ng x h/ml) compared with the 6 mg Q12H capsule dose, with markedly
      less fluctuation between peak and trough plasma levels (80% at 20 cm2 versus 620%
      at 1.5 mg Q12H). Plasma butyrylcholinesterase inhibition rose slowly after patch
      administration, whereas two distinct peaks were seen after capsule
      administration. Average exposure with the 10 cm2 patch was comparable to the
      highest capsule dose (6 mg Q12H, i.e., 12 mg/day).

PMID- 17522597
TI  - Model-based drug development.
AB  - The low productivity and escalating costs of drug development have been well
      documented over the past several years. Less than 10% of new compounds that enter
      clinical trials ultimately make it to the market, and many more fail in the
      preclinical stages of development. These challenges in the "critical path" of
      drug development are discussed in a 2004 publication by the US Food and Drug
      Administration. The document emphasizes new tools and various opportunities to
      improve drug development. One of the opportunities recommended is the application
      of "model-based drug development (MBDD)." This paper discusses what constitutes
      the key elements of MBDD and how these elements should fit together to inform
      drug development strategy and decision-making.

PMID- 17522598
TI  - Dietary supplementation with beta-glucan enriched oat bran increases faecal
      concentration of carboxylic acids in healthy subjects.
AB  - BACKGROUND/OBJECTIVE: Carboxylic acids (CAs), especially butyric acid, have been
      suggested to counteract colonic diseases, such as ulcerative colitis and colon
      cancer. Colonic formation of CAs can be influenced by the diet, but the
      concentrations and pattern formed need to be evaluated for different food
      products in humans. To elucidate how the colonic concentration of CAs in healthy
      subjects is influenced by dietary supplementation with oat bran, and whether the
      concentration varies over time and during consecutive days. SUBJECTS/METHODS:
      Twenty-five healthy subjects (age 24+/-1.3) were recruited to the study. The
      subjects were given 40 g beta-glucan enriched oat bran per day, corresponding to
      20 g dietary fibre, in 4 slices of bread. CAs were analysed in faeces during
      three consecutive days after 0, 4, 8 and 12 weeks on this diet. RESULTS: The
      concentration of acetic, propionic, butyric, isobutyric and isovaleric acid was
      higher (P<0.05-0.001) after 8 weeks on the oat bran diet as compared with values
      at entry, whereas that of lactic acid was lower (P<0.05). After 12 weeks, the
      concentrations of acetic, propionic and isobutyric acid were still higher and
      that of lactic acid lower. The variation between individuals was considerable,
      whereas in the same individuals there was little variation. CONCLUSIONS: Oat bran
      increased the faecal concentration of CAs after 8 weeks, indicating an increased
      concentration also in the distal colon. The concentration of all main acids
      increased, except for lactic acid, which decreased. Oat bran may therefore have a
      preventive potential adjunct to colonic diseases.

PMID- 17522599
TI  - Whole flaxseeds but not sunflower seeds in rye bread reduce apparent
      digestibility of fat in healthy volunteers.
AB  - OBJECTIVE: The aim of this study was to measure the apparent digestibility of fat
      and the transit time upon addition of whole sunflower seeds (SU) or flaxseeds
      (FL) to rye breads consumed as part of a whole diet. METHOD: In a randomized
      crossover study, gross intake and faecal excretion of fat and energy were
      measured in 11 young healthy men aged 24.6+/-2.7 years. During each 7 days
      intervention periods, the subjects received a basal diet plus 300 g of one of
      four rye breads: (1) rye bread; (2) rye bread with SU; (3) rye bread with FL; (4)
      low extraction rate rye bread with SU and FL. Fat binding properties of rye
      breads (1) and (3) were determined by in vitro digestion. RESULTS: Addition of
      whole SU or FL to breads increased daily gross intake of fat and energy
      (P<0.001). The amounts of apparently digested fat (g/day) and energy were lowered
      when subjects consumed the SU or FL rye bread (P<0.001). The effect on energy
      digestibility of FL was more pronounced than that of SU. The in vitro fat
      digestibility of rye breads and whole diets show fat-binding properties of FL
      when compared to the rye bread diet (P<0.05). CONCLUSIONS: Enrichment of bread
      with whole FL does not appear to result in increased fat and energy intake when
      added to breads, but the results rather indicate an impairment of nutrient
      utilization.

PMID- 17522600
TI  - Prenatal iron supplementation in rural Vietnam.
AB  - OBJECTIVE: To assess the potential impact of a national iron supplementation
      programme in rural Vietnam. METHODS: The study included questionnaires, focus
      group discussions of pregnant women and key informant interviews, together with
      measurements of haemoglobin (Hb) and a stool examination for soil-transmitted
      helminths. RESULTS: Iron supplementation significantly increased Hb concentration
      among participants in the second and third trimesters by 0.4 and 0.7 g/dl,
      respectively (P=0.017 and P<0.001). The risk of anaemia (Hb <10.0 g/dl) was
      increased significantly by hookworm infestation (P=0.041) and in summer season
      (P=0.001) and was decreased significantly by taking iron tablets (P=0.041).
      CONCLUSIONS: The results of this study show that an iron supplementation
      programme is beneficial as a part of a comprehensive anaemia programme for
      pregnant women in these communities. These results will be useful for developing
      improved iron-deficiency anaemia control programs for pregnant women.

PMID- 17522601
TI  - Association between decreased vitamin levels and MTHFR, MTR and MTRR gene
      polymorphisms as determinants for elevated total homocysteine concentrations in
      pregnant women.
AB  - OBJECTIVES: To examine the association between methylenetetrahydrofolate
      reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and
      methionine synthase reductase (MTRR) A66G gene polymorphisms and total
      homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S
      adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions
      with folate or cobalamin (Cbl) status. SUBJECTS/METHODS: Two hundred seventy-five
      healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy,
      MMA, SAM and SAH were measured in serum specimens. The genotypes for
      polymorphisms were determined by PCR-restriction fragment length polymorphism
      (RFLP). RESULTS: Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were
      the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were
      the predictors of SAM/SAH ratio and MMA levels, respectively. The gene
      polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels
      of serum folate were associated with elevated tHcy in pregnant women,
      independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T
      allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated
      with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR
      A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l.
      CONCLUSIONS: Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were
      the determinants for tHcy levels. The interaction between low levels of serum Cbl
      and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with
      increased tHcy.

PMID- 17522602
TI  - Physical activity level in healthy free-living Japanese estimated by doubly
      labelled water method and International Physical Activity Questionnaire.
AB  - OBJECTIVE: To measure total energy expenditure (TEE) for normal healthy Japanese
      by the doubly labelled water (DLW), and to compare the physical activity level
      (PAL) among categories classified by the categories used in daily reference
      intake (DRI), Japan and the International Physical Activity Questionnaire (IPAQ).
      SUBJECTS AND METHODS: A total of 150 healthy Japanese men and women aged 20- to
      59-year-old living in four districts of Japan. TEE was measured by the DLW
      method, and the PAL was calculated from TEE divided by basal metabolic rate.
      Simultaneously with TEE measurement, the PAL was assessed employing the
      categories used in DRI, Japan and IPAQ. RESULTS: The average TEE and PAL were
      10.78+/-1.67 MJ/day and 1.72+/-0.22 for males and 8.37+/-1.30 MJ/day and 1.72+/
      0.27 for females, respectively. The subjects in the highly active categories
      assessed by both DRI and IPAQ showed significantly higher PAL compared with less
      active categories. However, PALs among light and moderate categories by DRI, and
      insufficient and sufficiently active by IPAQ were not significantly different.
      CONCLUSIONS: In developed countries, highly active subjects could be assessed by
      a simple questionnaire. However, the questionnaire should be improved to clarify
      the sedentary to moderately active subjects by assessing carefully very light to
      moderate physical activity.

PMID- 17522603
TI  - Second meal effects of dietary calcium and vitamin D.
AB  - OBJECTIVE: To determine the second meal effects of calcium and vitamin D on
      postprandial glucose, insulin, non-esterified fatty acids (NEFA) and glycerol.
      METHODS: Eight volunteers aged (mean+/-s.e.m.) 55.5+/-1.2 years and body mass
      index 29.0+/-1.6 kg/m(2), completed a randomized within-subject design that
      compared a low calcium-low vitamin D breakfast and an isocaloric high calcium
      high vitamin D breakfast (HCB). Four hours following each breakfast, a very low
      calcium standard lunch was ingested. Serial blood collections were made on the
      hour over a duration of 8 h. Postprandial responses were calculated as the
      percentage change (Delta) from the fasting value for breakfast meals, and the 4th
      hour breakfast value for each lunch, respectively. Non-parametric tests of
      significance were employed. RESULTS: The change in glucose, insulin, serum
      ionized calcium (iCa(2+)) and intact parathyroid hormone was not different
      between the two breakfasts, or the two lunches. However, HCB resulted in a lesser
      suppression of NEFA that significantly carried over to lunch (P=0.036, Wilcoxon
      test). A similar pattern of change in glycerol did not attain overall statistical
      significance. DeltaNEFA and Deltaglycerol were related at lunch (Spearman's
      r=0.52, P=0.04). Relative to breakfast, both lunches resulted in significantly
      higher glucose and insulin responses (P=0.011, Wilcoxon test). CONCLUSIONS: The
      data are suggestive of second meal effects of calcium and vitamin D. Our
      observations of higher glucose and insulin after lunch may include the
      involvement of second meal factors as well.

PMID- 17522604
TI  - Effect of a moderately hypoenergetic Mediterranean diet and exercise program on
      body cell mass and cardiovascular risk factors in obese women.
AB  - OBJECTIVE: To assess the effects of a moderately hypoenergetic Mediterranean diet
      (MHMD) and exercise program on body cell mass (BCM) and cardiovascular disease
      risk factors in obese women. SUBJECTS/METHODS: Forty-seven obese women, 39.7+/
      13.2 years of age, with a body mass index (BMI)=30.7+/-6.0 kg/m(2), completed the
      study. The following were measured at baseline, 2 and 4 months: BCM, BCM index
      (BCMI), body weight, BMI, fat-free mass (FFM), fat mass (FM), total body water
      (TBW), extracellular water (ECW) and intracellular water (ICW) using
      bioelectrical impedance analysis; fasting blood glucose (FBG), serum total
      cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations; systolic
      (SBP) and diastolic (DBP) blood pressure. RESULTS: Body weight, BMI, FM, TC and
      TG significantly decreased (P<0.001; P<0.002 (TG)) at 2 and 4 months. FFM, TBW,
      ECW, FBG and DBP significantly decreased at 2 months (P<0.05 (FFM); P<0.001). LDL
      C significantly decreased (P<0.001), while HDL-C significantly increased
      (P<0.002) at 4 months. BCM, BCMI, ICW and SBP remained stable over time.
      CONCLUSION: BCM was preserved and cardiovascular disease risk factors improved in
      obese women placed on a MHMD and exercise program for 4 months.

PMID- 17522605
TI  - Drinking pattern and mortality in Danish nurses.
AB  - BACKGROUND/OBJECTIVE: Moderate alcohol consumption has beneficial effects on
      survival. Sex differences, however, have been suggested implying less beneficial
      effect among women. We examined the impact of alcohol consumed on weekdays and at
      weekends, respectively, on risk of death among women. SUBJECTS AND METHODS: At
      baseline in 1993, a total of 17 772 female members of the Danish Nurse
      Association completed questionnaires on alcohol intake and other lifestyle
      factors. The influence of alcohol intake on risk of death was analyzed using Cox
      proportional hazard model. RESULTS: Alcohol intake of 1-3 drinks per week was
      associated with the lowest risk of death. Intake above six drinks per weekend
      (Friday through Sunday) increased risk of death from all causes by 3% for each
      additional drink consumed per weekend (corresponding to an increased risk by 9%
      per drink per weekend day). Consumption of one or more drinks per weekday
      (Monday, Tuesday, Wednesday or Thursday) increased risk by 4% for each additional
      drink consumed per day. CONCLUSIONS: The results indicated an increasing risk of
      death for intake above six drinks per weekend and of one or more drinks per
      weekday.

PMID- 17522606
TI  - Trends of socioeconomic differences in daily vegetable consumption, 1979-2002.
AB  - BACKGROUND: Studies from different time periods have shown that consumption of
      vegetables is more common in higher socioeconomic groups and among women.
      However, there are only few studies of changes of socioeconomic differences in
      vegetable consumption over time. Our aim was to determine whether socioeconomic
      differences, measured by educational level and household income, in daily
      vegetable consumption have increased, decreased or been stable over the last two
      decades among Finnish men and women. METHODS: Data on daily consumption of fresh
      vegetables were derived from repeated annual cross-sectional surveys performed
      among representative samples of Finnish working aged (15-64 years) population.
      Data from the years 1979-2002 were linked with data on education and household
      income from Statistics Finland. Those under 25 years and all students were
      excluded, giving a total of 69 383 respondents. The main analyses were conducted
      with logistic regression. RESULTS: Daily consumption of fresh vegetables became
      overall more prevalent during the study period. Daily consumption of fresh
      vegetables was more common among those with higher education and higher income
      during the whole study period. Both educational level and household income
      differences in daily vegetable consumption slightly narrowed since 1979 among men
      and women. CONCLUSIONS: Women with high socioeconomic position have been initial
      trend setters, but the prevalence of daily consumers of vegetables in these
      groups has not increased since the early 1990s. The prevalence of daily
      consumption of fresh vegetables has increased more in lower educational and
      income groups during the 1980s and 1990s along with narrowing socioeconomic
      differences.

PMID- 17522607
TI  - Effects of two marine dietary supplements with high calcium content on calcium
      metabolism and biochemical marker of bone resorption.
AB  - BACKGROUND/OBJECTIVE: Calcium is essential for the bone metabolism but daily
      calcium requirements are not met in a significant proportion of the population.
      Fortunately, oral calcium supplementation can help to meet these needs; however,
      the calcium bioavailability depends on the calcium sources. The calcium
      absorption and bioavailability of dietary supplements from marine sources are not
      known. The objectives of this study were to evaluate the effects of two marine
      dietary supplements with a high calcium content: a fishbone powder (Phoscalim)
      and a ray cartilage hydrolysate (Glycollagene), in comparison with milk, and a
      placebo (maltodextrin), on calcium metabolism and a biochemical marker of bone
      resorption, using the oral calcium tolerance test. SUBJECTS: Twenty male
      volunteers were randomized to eat 836 mg of calcium from different sources
      compared to maltodextrin during a Latin square study. Serum calcium
      concentrations and other parameters of the calcium metabolism, such as serum
      intact parathyroid hormone (iPTH) and serum C telopeptides (s-CTX), were measured
      after an acute oral calcium load based on the Pak protocol. RESULTS: An increase
      in serum-corrected calcium areas under the curve (AUC) occurred with Phoscalim
      and Glycollagene when compared to milk. Significantly lower iPTH concentrations
      were observed with Glycollagene than with milk at T0+1 h, T0+3 h, T0+6 h and with
      Phoscalim than with milk at T0+6 h. A significantly lower s-CTX concentration was
      observed with Glycollagene than with milk and Phoscalim at T0+6 h. Furthermore,
      the urinary calcium/creatinine ratio increased significantly more with
      Glycollagen than with milk in T0 h+3 h and T3 h+6 h. CONCLUSION: These two
      dietary supplements from marine sources constitute oral calcium sources when
      compared to milk on calcium absorption and bone resorption markers on short time.

PMID- 17522608
TI  - Personal, social and environmental predictors of daily fruit and vegetable intake
      in 11-year-old children in nine European countries.
AB  - OBJECTIVE: To investigate potential personal, social and physical environmental
      predictors of daily fruit intake and daily vegetable intake in 11-year-old boys
      and girls in nine European countries. SUBJECTS: The total sample size was 13 305
      (90.4% participation rate). RESULTS: Overall, 43.2% of the children reported to
      eat fruit every day, 46.1% reported to eat vegetables every day. Daily fruit
      intake and daily vegetable intake was mainly associated with knowledge of the
      national recommendations, positive self-efficacy, positive liking and preference,
      parental modeling and demand and bringing fruit to school (odds ratio between
      1.40 and 2.42, P<0.02). These factors were associated fairly consistently with
      daily fruit intake across all nine European countries, implying that a rather
      uniform intervention strategy to promote fruit can be used across Europe. For
      vegetables, the pattern was, however, less consistent. Differences between
      countries in cooking and preparing vegetables might be responsible for this
      larger diversity. CONCLUSIONS: This study showed that especially a combination of
      personal and social factors is related to daily fruit and vegetable intake in
      schoolchildren. This shows that a comprehensive multilevel intervention strategy
      based upon a series of individual and social correlates will be most promising in
      the promotion of daily fruit and vegetable intake in children.

PMID- 17522610
TI  - Effects of a short-term intervention with a paleolithic diet in healthy
      volunteers.
AB  - OBJECTIVES: Prevention of cardiovascular diseases by paleolithic or hunter
      gatherer diets has been discussed during recent years. METHODS: Our aim was to
      assess the effect of a paleolithic diet in a pilot study on healthy volunteers
      during 3 weeks. The intention was to include 20 subjects, of whom 14 fulfilled
      the study. Complete dietary assessment was available for six subjects. RESULTS:
      Mean weight decreased by 2.3 kg (P<0.001), body mass index by 0.8 (P<0.001),
      waist circumference by 0.5 cm (P=0.001), systolic blood pressure by 3 mm Hg
      (P=0.03) and plasminogen activator inhibitor-1 by 72% (P=0.020). Regarding
      nutrient intake, intake of energy decreased by 36%, and other effects were also
      observed, both favourable (fat composition, antioxidants, potassium-sodium rate)
      and unfavourable (calcium). CONCLUSION: This short-term intervention showed some
      favourable effects by the diet, but further studies, including control group, are
      needed.

PMID- 17522609
TI  - The efficacy of micronutrient supplementation in reducing the prevalence of
      anaemia and deficiencies of zinc and iron among adolescents in Sri Lanka.
AB  - OBJECTIVE: To determine the effectiveness of combined iron and zinc over the iron
      or zinc-only supplementation in correcting deficiency and possible interactive
      effects in a group of adolescent school children. SUBJECTS AND METHODS:
      Schoolchildren (n=821) of 12-16 years of age were randomized into four groups and
      supplemented with iron (50 mg/day), zinc (14 mg/day), iron+zinc or placebo
      capsules 5 days per week for 24 weeks. Anthropometry, and haemoglobin (Hb), serum
      zinc (SZn) and serum ferritin (SF) concentrations were determined before and
      after the intervention. RESULTS: There were no significant effects between-groups
      in their weight, height and Hb concentrations with the intervention when compared
      with the placebo group. Iron-only and combination-supplemented groups had reached
      mean SF concentrations of 55.1 microg/l with no difference between them (P=0.99).
      The zinc-only group had a mean change of 4.3 micromol//l whereas the combine
      supplemented group had a mean change of 4.0 micromol/l (P=0.82). The prevalence
      of anaemia was found to be 70.3% in the iron group at baseline; this was reduced
      to 14.5% after the supplementation. In the combine-supplemented group anaemia,
      prevalence was reduced from 64.8 to 19.3%. CONCLUSIONS: Zinc alone or in
      combination with iron has not shown a significant improvement in growth in
      adolescence. Severe and moderate forms of anaemia were successfully treated in
      children who received iron supplementation. Initial high prevalence of low SZn
      and iron stores was significantly improved with micronutrient supplementation.

PMID- 17522611
TI  - Adjusting for energy intake in dietary pattern investigations using principal
      components analysis.
AB  - OBJECTIVE: The effect of energy adjustment on variables entered into principal
      component analysis (PCA) to derive dietary patterns has received little
      attention. DESIGN AND METHODS: As part of regular self-completion questionnaires,
      used in the Avon Longitudinal Study of Parents and Children, pregnant women were
      asked to record the frequency of consumption of a variety of food items. A total
      of 12 053 women completed the questionnaire. Individual dietary types were
      identified using PCA, before and after adjusting the food variables for energy
      intake. Associations with estimated nutrient intakes and with birthweight were
      examined for the two solutions and when energy adjustment was performed at a
      later stage of the analysis. RESULTS: Slight differences were seen in terms of
      the components extracted and the factor loadings obtained. The associations with
      nutrient intakes showed that there was a general reduction in the size of the
      correlation coefficients for the energy-adjusted components compared to the
      unadjusted components. There did not appear to be any difference in the size of
      the effects of the dietary pattern scores on birthweight, whether energy was
      adjusted for before entry into the PCA or after. CONCLUSIONS: In this sample, it
      is not necessary to adjust for energy intake before entry into a PCA analysis to
      determine dietary patterns when using food frequency questionnaire data. Effects
      of energy intake can be determined at a later stage in the analytical
      process.This study determines the effect of adjusting for energy on dietary
      patterns resulting from PCA and the subsequent effect on future outcomes.

PMID- 17522612
TI  - Prospective study of coffee consumption and risk of Parkinson's disease.
AB  - OBJECTIVE: To examine the prediction of coffee consumption on the incidence of
      Parkinson's disease. SUBJECTS AND METHODS: The study population comprised 6710
      men and women, aged 50-79 years and free from Parkinson's disease at the
      baseline. At baseline, enquiries were made about coffee consumption in a self
      administered questionnaire as the average number of cups per day. During a 22
      year follow-up, 101 incident cases of Parkinson's disease occurred. Parkinson's
      disease cases were identified through a nationwide registry of patients receiving
      medication reimbursement, which is based on certificates from neurologist.
      RESULTS: After adjustments for age, sex, marital status, education, community
      density, alcohol consumption, leisure-time physical activity, smoking, body mass
      index, hypertension and serum cholesterol, the relative risk for subjects
      drinking 10 or more cups of coffee per day compared with non-drinkers was 0.26
      (95% confidence interval 0.07-0.99, P-value for trend=0.18). The association was
      stronger among overweight persons and among persons with lower serum cholesterol
      level (P-value for interaction=0.04 and 0.03, respectively). CONCLUSIONS: The
      results support the hypothesis that coffee consumption reduces the risk of
      Parkinson's disease, but protective effect of coffee may vary by exposure to
      other factors.

PMID- 17522613
TI  - Removing lactose from milk does not delay bowel function or harden stool
      consistency in lactose-tolerant women.
AB  - OBJECTIVES: To investigate whether removing lactose from milk delays bowel
      function in lactose-tolerant women. We also examined how well the participants'
      subjective evaluation of the stool consistency according to the Bristol Stool
      Form Scale correlated with values obtained by dry matter analysis and
      penetrometry. SUBJECTS AND METHODS: A randomized double-blind cross-over trial.
      Thirty-three lactose-tolerant women consumed, in random order, 800 ml of lactose
      free or ordinary milk per day for 2 weeks, with their main meal, but otherwise
      followed a lactose-free diet. The subjects estimated stool consistency according
      to the Bristol Stool Form Scale, registered stool frequency and gastrointestinal
      symptoms and collected stool samples. RESULTS: The mean intake of lactose was 3.5
      and 38.4 g/day during the lactose-free and the ordinary milk periods,
      respectively. There were no statistically significant differences between the
      lactose-free and the ordinary milk periods in stool frequency, gastrointestinal
      symptoms, stool hardness or faecal dry matter. Faecal pH was lower during the
      lactose-free milk period than in the ordinary milk period. The subjective
      estimation of stool hardness correlated well with the values obtained by dry
      matter analysis and penetrometry. CONCLUSIONS: Lactose-free milk does not delay
      bowel function in lactose-tolerant women. The Bristol Stool Form Scale is a
      useful method of evaluating stool hardness.

PMID- 17522614
TI  - Effect of fasting on young adults who have symptoms of hypoglycemia in the
      absence of frequent meals.
AB  - BACKGROUND AND OBJECTIVES: Among otherwise healthy adults, there is a subgroup of
      individuals who develop symptoms of hypoglycemia during episodes of food
      restriction. The aim of the present study was to investigate whether such
      individuals develop hypoglycemia or react abnormally in other metabolic aspects
      during a 24-hour fast. SUBJECTS AND METHODS: Ninety medical students were asked
      if they wanted to participate. Sixteen were selected; none dropped out. A 24-hour
      fast was performed at a hospital ward. Blood samples and questionnaires were
      taken at eight specific times. RESULT: During the fast, the sensitive group
      reported significantly higher scores on 'irritation' and 'shakiness'. However, no
      hypoglycemia occurred and the lowest detected blood glucose concentration was 3.7
      mmol/l. There were no differences between the groups in plasma glucose, cortisol,
      growth hormone (GH), insulin, beta-hydroxybutyrate (beta-OH) and lactate levels.
      The blood pressures and heart rates were also similar. CONCLUSIONS: Adults,
      despite subjective signs of hypoglycemia, can fast without any metabolic or
      endocrine derangement.

PMID- 17522615
TI  - Effects of GI vs content of cereal fibre of the evening meal on glucose tolerance
      at a subsequent standardized breakfast.
AB  - OBJECTIVE: To investigate if the improved glucose tolerance previously observed
      at breakfast following an evening meal with boiled barley kernels derives from
      colonic events related to the fermentation of the elevated amounts of
      indigestible carbohydrates present and/or from the low-GI features.
      SUBJECTS/METHODS: Twenty healthy volunteers aged 19-30 years. DESIGN: High-GI
      white wheat bread (WWB), WWB+barley dietary fibre (DF) corresponding to the DF
      content of barley kernels, low-GI spaghetti+ barley DF, spaghetti+double amounts
      of barley DF (2(*)DF), spaghetti+oat DF, or whole grain barley flour porridge,
      were provided as late evening meals. At a subsequent standardised WWB breakfast,
      B-glucose, s-insulin, p-SCFA, p-FFA, and breath hydrogen (H(2)) were measured.
      RESULTS: The B-glucose response (incremental areas under the curves (IAUC) 0-120
      min and total areas under the curves 0-180 min) to the standardized breakfast was
      significantly lower after consuming spaghetti+2*DF in the evening compared with
      barley porridge (P=0.012). The spaghetti+2*DF meal also resulted in the highest
      breath H(2) excretion (P<0.02). The glucose IAUC (0-120 min) after the
      standardized breakfast was positively correlated to fasting p-FFA (r=0.29,
      P<0.02), and the total glucose area (0-180 min) was negatively correlated to the
      p-propionate level (0-30 min) (r=-0.24, P<0.02). CONCLUSIONS: The prolonged
      digestive and absorptive phase per se, like with a low-glycaemic index (GI)
      spaghetti evening meal, did not induce overnight benefits on glucose tolerance.
      Addition of barley DF in high amounts (2*DF) was required to improve overnight
      glucose tolerance. The correlations observed between glycaemia and p-propionate
      implicate colonic fermentation as a modulator of glucose tolerance through a
      mechanism leading to suppressed free fatty acids levels. It is proposed that the
      overnight benefits on glucose tolerance previously reported for boiled barley
      kernels is mediated through colonic fermentation of the prebiotic carbohydrates
      present in this product.

PMID- 17522616
TI  - Relationship between the change in overweight status from childhood to
      adolescence and metabolic syndrome phenotypes: a 9-year retrospective study.
AB  - OBJECTIVE: To evaluate how the changes in overweight status from childhood to
      adolescence are related to metabolic syndrome phenotypes in adolescents. SUBJECTS
      AND METHODS: A total 375 adolescents aged 16 years. The overweight status from
      childhood to adolescence (from 7 years of age to 16 years) was determined by body
      mass index (BMI, kg/m(2)) calculated from records of the School Physical
      Examination data. The change in body weight was classified into four groups:
      normal weight to normal weight (NW-NW); overweight to normal (OW-NW); normal to
      overweight (NW-OW); overweight to overweight (OW-OW). Metabolic syndrome
      phenotypes were examined from a cross-sectional survey. RESULTS: The mean values
      of all phenotypes except for body fatness (BMI and waist) and the cluster score
      of phenotypes at 16 years of age were not different between the NW-NW group and
      the OW-NW group, nor between the NW-OW group and the OW-OW group. However, the
      score as well as the level of body fatness and blood glucose were significantly
      different between current overweight and normal adolescents regardless of
      overweight status during childhood (P<0.05). CONCLUSION: There was a linear
      relationship between overweight status during childhood and metabolic syndrome
      phenotypes in adolescence but current overweight status (adolescence overweight)
      was more closely related to the adolescent risk of metabolic syndrome than
      childhood overweight status.

PMID- 17522617
TI  - Associations between active commuting to school, fat mass and lifestyle factors
      in adolescents: the Kiel Obesity Prevention Study (KOPS).
AB  - OBJECTIVE: To examine possible associations between active commuting (walking or
      cycling) to school, parameters of adiposity and lifestyle factors in 14-year-old
      adolescents of the Kiel Obesity Prevention Study. SUBJECTS: A total of 626 14
      year-old adolescents. METHODS: Measured body mass index (BMI), fat mass (FM),
      distance to school as well as self-reported modes and duration of commuting to
      school, time spent in structured and unstructured physical activities (PAs),
      media use, nutrition, alcohol consumption and smoking. RESULTS: Parameters of
      adiposity did not differ between different commuting modes after stratifying by
      gender. Active commuters reported higher overall PA, which was caused by
      commuting activity and time spent in unstructured PA in girls and just by
      commuting activity in boys. In active commuters, 28.4% of overall PA was
      explained by commuting activity. Additionally, TV viewing was lower in active
      commuters. Compared to their inactively commuting counterparts, actively
      commuting boys were less likely to smoke. After controlling for potential
      confounders the interaction term 'active commuting by distance to school' and
      'time spent in structured PA' were independent predictors of FM, whereas active
      commuting by itself showed no effect. CONCLUSION: The present data suggest that
      active commuting to school per se does not affect FM or BMI until considering
      distance to school. Increasing walking or cycling distance results in decreasing
      FM. However, the everyday need to get to and from school may enhance adolescents'
      overall PA.

PMID- 17522618
TI  - The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total
      serum homocysteine level in orthotopic liver transplant recipients: a double
      blind placebo-controlled study.
AB  - OBJECTIVE: Hyperhomocysteinemia is a described risk factor of cardiovascular
      diseases. The aim of this study was the treatment of hyperhomocysteinemia in
      liver transplant recipients with L-5-methyltetrahydrofolate (L-5-MTHF; 1 mg) vs
      folic acid (1 mg) vs placebo in a double-blind placebo-controlled study and to
      compare the relative responsiveness of these patients to L-5-MTHF and folic acid.
      SUBJECTS/METHODS: Patients were recruited from Hepatology-Transplantation-Unit at
      Johann Wolfgang Goethe-University, Frankfurt. Sixty patients were included in
      this study and 12 patients dropped out for different reasons. The patients were
      treated over 8 weeks with supplemental L-5-MTHF or folic acid or placebo. Serum
      homocysteine (HCY) was analyzed with high-performance liquid chromatography
      (HPLC) beside routine lab tests. RESULTS: We observed only a significant decrease
      of total serum HCY in the L-5-MTHF group during the study period (at week 0: 15+/
      7.7 microM; after 8 weeks treatment: 9.41+/-2.6 microM, P<0.001). There was no
      significant decrease of total serum HCY neither in the folic acid group nor in
      the placebo group. CONCLUSION: The effects of L-5-MTHF are significantly more
      potent than folic acid itself. Therefore, lowering serum HCY in liver transplant
      recipients is effective with L-5-MTHF.

PMID- 17522619
TI  - Effect of intradialytic parenteral nutrition in patients with malnutrition
      inflammation complex syndrome on body weight, inflammation, serum lipids and
      adipocytokines: results from a pilot study.
AB  - OBJECTIVE: Evaluation of the influence of intradialytic parenteral nutrition
      (IDPN) in patients suffering from Malnutrition-Inflammation Complex Syndrome
      (MICS) on nutritional status, inflammation, adipocytokines and serum lipids.
      SUBJECTS: Six patients with MICS were assigned to IDPN, whereas six patients
      matched for age, sex, body mass index (BMI) and co-morbidity without malnutrition
      served as controls. Patients were recruited from Outpatient Dialysis Unit,
      Medical University Innsbruck and from Dialysis Unit, Hospital Feldkirch. RESULTS:
      In all patients with IDPN, dry body weight increased during the interventional
      period whereas body weight remained stable in patients without IDPN. Tumor
      necrosis factor (TNF)-alpha levels were higher in patients with MICS compared
      with controls at all time points. Total cholesterol, LDL- and HDL-levels
      significantly increased during dialysis at all time points in controls but not in
      patients with MICS. Albumin, C-reactive protein, interleukin-6 (IL-6), soluble
      interleukin-2 receptor (sIL-2R) and adipocytokines did not differ between
      patients and controls during the study period. CONCLUSIONS: IDPN in patients with
      MICS increases body weight despite not influencing inflammatory status.
      Furthermore, IDPN does not induce a pro-atherogenic lipid composition enhancing
      the risk for atherosclerosis. Thus, IDPN is a safe and effective treatment of
      malnutrition in patients with MICS.

PMID- 17522620
TI  - Identification of novel deletions of 15q11q13 in Angelman syndrome by array-CGH:
      molecular characterization and genotype-phenotype correlations.
AB  - Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental
      retardation, absent speech, ataxia, and a happy disposition. Deletions of the
      15q11q13 region are found in approximately 70% of AS patients. The deletions are
      sub-classified into class I and class II based on their sizes of approximately
      6.8 and approximately 6.0, respectively, with two different proximal breakpoints
      and a common distal breakpoint. Utilizing a chromosome 15-specific comparative
      genomic hybridization genomic microarray (array-CGH), we have identified,
      determined the deletion sizes, and mapped the breakpoints in a cohort of 44
      cases, to relate those breakpoints to the genomic architecture and derive more
      precise genotype-phenotype correlations. Interestingly four patients of the 44
      studied (9.1%) had novel and unusually large deletions, and are reported here.
      This is the first report of very large deletions of 15q11q13 resulting in AS; the
      largest deletion being >10.6 Mb. These novel deletions involve three different
      distal breakpoints, two of which have been earlier shown to be involved in the
      generation of isodicentric 15q chromosomes (idic15). Additionally, precise
      determination of the deletion breakpoints reveals the presence of directly
      oriented low-copy repeats (LCRs) flanking the recurrent and novel breakpoints.
      The LCRs are adequate in size, orientation, and homology to enable abnormal
      recombination events leading to deletions and duplications. This genomic
      organization provides evidence for a common mechanism for the generation of both
      common and rare deletion types. Larger deletions result in a loss of several
      genes outside the common Angelman syndrome-Prader-Willi syndrome (AS-PWS)
      critical interval, and a more severe phenotype.

PMID- 17522625
TI  - American Society of Gene Therapy 10th Annual Meeting, May 30-June 3, 2007,
      Seattle, Washington, USA. Abstracts.
AB  - Molecular Therapy (2007) doi:10.1038/sj.mt.6300198.

PMID- 17522621
TI  - No association of ERCC1 C8092A and T19007C polymorphisms to cancer risk: a meta
      analysis.
AB  - ERCC1 (excision repair cross complementation group 1) is a subunit of the
      nucleotide excision repair complex, which can perform DNA strand incision
      correction of DNA damage. Association studies on the ERCC1 polymorphisms (C8092A
      and T19007C) in cancer had shown conflicting results. We performed a meta
      analysis from all eligible case-control studies to assess the purported
      associations. Overall, the 19007C allele (3 853 patients and 4 349 controls)
      showed no significant effect on cancer risk compared to 19007T allele (P=0.39,
      odds ratio (OR)=0.95; 95% confidence interval (CI) 0.85-1.06,
      P(heterogeneity)=0.001) in all subjects. Meta-analysis under other genetic
      contrasts did not reveal any significant association of T19007C to cancer in all
      subjects, Caucasians and Asians. The 19007C allele (2 279 patients and 2 808
      controls) showed no significant effect on lung cancer risk compared to 19007T
      allele (P=0.72, OR=0.94, 95% CI 0.69-1.29, P(heterogeneity)=0.0001) in all
      subjects. No significant effect of 8092A allele (3 865 patients and 3 750
      controls) on cancer risk in all subjects (P=0.85, OR=1.01, 95% CI 0.94-1.08,
      P(heterogeneity)=0.92) and in Caucasians and Asians compare to 8092C. No
      evidences of association of C8092A (501 patients and 620 controls) to squamous
      cell carcinoma were found. The accumulated evidence indicated ERCC1 T19007C and
      C8092A might not be risk factors for cancer. Significant between-study
      heterogeneity existed in T19007C, which arose from a study showing significant
      protecting effect of 19007C allele compare to 19007T allele in smokers. More
      studies based on larger, stratified case-control population should be required to
      further evaluate the role of ERCC1 C8092A and T19007C polymorphisms in different
      cancer, especially in smokers.

PMID- 17522626
TI  - Association of the COMT val158met variant with antidepressant treatment response
      in major depression.
AB  - In several previous biochemical, pharmacological, and genetic studies, the
      catechol-O-methyltransferase (COMT) has been suggested to be involved in the
      pathogenesis as well as the pharmacological treatment of affective disorders. In
      the present study, 256 patients with major depression (DSM-IV) of Caucasian
      descent were genotyped for the functional COMT val158met polymorphism and
      characterized for clinical response to antidepressive pharmacological treatment
      as measured by intra-individual changes of Hamilton Depression (HAM-D-21) scores
      over 6 weeks. The COMT 158val/val genotype conferred a significant risk of worse
      response after 4-6 weeks of antidepressant treatment in patients with major
      depression (week 4: p=0.003; week 5: p<0.0001; week 6: p<0.0001) after Bonferroni
      correction for multiple comparisons. The present results strongly point toward a
      negative influence of the higher activity COMT 158val/val genotype on
      antidepressant treatment response during the first 6 weeks of pharmacological
      treatment in major depression, possibly conferred by consecutively decreased
      dopamine availability. This finding suggests a potentially beneficial effect of
      an antidepressive add-on therapy with substances increasing dopamine availability
      individually tailored according to COMT val158met genotype.

PMID- 17522627
TI  - Endogenous nociceptin (orphanin FQ) suppresses basal hedonic state and acute
      reward responses to methamphetamine and ethanol, but facilitates chronic
      responses.
AB  - The opioid peptide nociceptin (orphanin FQ) suppresses drug reward, drug self
      administration, and impedes some of the processes believed to underlie the
      transition to addiction. As virtually all previous studies have used
      administration of nociceptin receptor agonists to evaluate the role of nociceptin
      on addiction-like behavior, the current study used a pharmacological (nociceptin
      receptor antagonist) and genetic (nociceptin receptor knockout mice) approach to
      elucidate the role of endogenous nociceptin. The nociceptin receptor antagonist
      UFP-101 induced a modest place preference, and enhanced the conditioned place
      preference induced by methamphetamine. In agreement with this, nociceptin
      receptor knockout mice had slightly enhanced methamphetamine and ethanol
      conditioned place preferences compared to wild-type mice. This effect did not
      appear to depend on differences in learning ability, as nociceptin receptor
      knockout mice had slightly weaker-conditioned place aversions to lithium
      chloride, the kappa-opioid receptor agonist, U50488H, and the general opiate
      antagonist, naloxone. The development of behavioral sensitization to
      methamphetamine was lower in nociceptin receptor knockout mice, and attenuated by
      UFP-101 administration to wild-type mice. Additionally, ethanol consumption and
      preference in a two-bottle choice test was lower in nociceptin receptor knockout
      mice, though ethanol-stimulated locomotion was stronger. Whereas the rewarding
      effect of methamphetamine and ethanol following chronic treatment, as measured by
      place conditioning, strengthened in wild-type mice, this effect was absent in
      nociceptin receptor knockout mice. These results suggest that endogenous N/OFQ
      suppresses basal and drug-stimulated increases in hedonic state, and plays either
      a permissive or facilitatory role in the development of addiction.

PMID- 17522628
TI  - Glycine uptake regulates hippocampal network activity via glycine receptor
      mediated tonic inhibition.
AB  - Functional glycine receptors (GlyRs) are enriched in the hippocampus, but their
      role in hippocampal function remains unclear. Since the concentration of ambient
      glycine is determined by the presence of powerful glycine transporter (GlyT), we
      blocked the reuptake of glycine in hippocampal slices to examine the role of
      GlyRs. Antagonists of GlyT type 1 (GlyT1) but not that of GlyT type 2 (GlyT2)
      induced excitatory postsynaptic potential (EPSP)-spike depression, which was
      reversed by the specific GlyR antagonist strychnine. Moreover, endogenously
      elevating the glycine concentration with the GlyT1 antagonists facilitated NMDA
      receptor-dependent long-term potentiation induction, and elicited a strychnine
      sensitive chloride current. In addition, impairment of glial function with
      fluoroacetate blocked the effect of GlyT1 antagonists on the EPSP-spike curve.
      Furthermore, pretreatment with sarcosine was effective in controlling
      pentylenetetrazol-induced seizures. These results indicate an essential role of
      GlyTs in fine-tuning tonic activation of GlyRs and suggest a potential role of
      GlyR-dependent EPSP-spike depression in hippocampal network stability.

PMID- 17522629
TI  - Lateral habenula as a source of negative reward signals in dopamine neurons.
AB  - Midbrain dopamine neurons are key components of the brain's reward system, which
      is thought to guide reward-seeking behaviours. Although recent studies have shown
      how dopamine neurons respond to rewards and sensory stimuli predicting reward, it
      is unclear which parts of the brain provide dopamine neurons with signals
      necessary for these actions. Here we show that the primate lateral habenula, part
      of the structure called the epithalamus, is a major candidate for a source of
      negative reward-related signals in dopamine neurons. We recorded the activity of
      habenula neurons and dopamine neurons while rhesus monkeys were performing a
      visually guided saccade task with positionally biased reward outcomes. Many
      habenula neurons were excited by a no-reward-predicting target and inhibited by a
      reward-predicting target. In contrast, dopamine neurons were excited and
      inhibited by reward-predicting and no-reward-predicting targets, respectively.
      Each time the rewarded and unrewarded positions were reversed, both habenula and
      dopamine neurons reversed their responses as the bias in saccade latency
      reversed. In unrewarded trials, the excitation of habenula neurons started
      earlier than the inhibition of dopamine neurons. Furthermore, weak electrical
      stimulation of the lateral habenula elicited strong inhibitions in dopamine
      neurons. These results suggest that the inhibitory input from the lateral
      habenula plays an important role in determining the reward-related activity of
      dopamine neurons.

PMID- 17522630
TI  - Mechanism of coupled folding and binding of an intrinsically disordered protein.
AB  - Protein folding and binding are analogous processes, in which the protein
      'searches' for favourable intramolecular or intermolecular interactions on a
      funnelled energy landscape. Many eukaryotic proteins are disordered under
      physiological conditions, and fold into ordered structures only on binding to
      their cellular targets. The mechanism by which folding is coupled to binding is
      poorly understood, but it has been hypothesized on theoretical grounds that the
      binding kinetics may be enhanced by a 'fly-casting' effect, where the disordered
      protein binds weakly and non-specifically to its target and folds as it
      approaches the cognate binding site. Here we show, using NMR titrations and (15)N
      relaxation dispersion, that the phosphorylated kinase inducible activation domain
      (pKID) of the transcription factor CREB forms an ensemble of transient encounter
      complexes on binding to the KIX domain of the CREB binding protein. The encounter
      complexes are stabilized primarily by non-specific hydrophobic contacts, and
      evolve by way of an intermediate to the fully bound state without dissociation
      from KIX. The carboxy-terminal helix of pKID is only partially folded in the
      intermediate, and becomes stabilized by intermolecular interactions formed in the
      final bound state. Future applications of our method will provide new
      understanding of the molecular mechanisms by which intrinsically disordered
      proteins perform their diverse biological functions.

PMID- 17522634
TI  - An unwieldy hybrid.

PMID- 17522635
TI  - Unwise branding.

PMID- 17522638
TI  - Plans forge ahead for better weather monitoring.

PMID- 17522636
TI  - Nobels in dubious causes.

PMID- 17522639
TI  - Celebrity genomes alarm researchers.

PMID- 17522640
TI  - Website homes in on climate hazards.

PMID- 17522641
TI  - Help flies in for human genome.

PMID- 17522642
TI  - NIH presents the mind of a child.

PMID- 17522643
TI  - Japan centres aim to put science in premier league.

PMID- 17522645
TI  - Darwin sceptic says views cost tenure.

PMID- 17522648
TI  - London calling.

PMID- 17522650
TI  - Quantum cryptography: seeking absolute security.

PMID- 17522649
TI  - Neuroscience: the molecular wake-up call.

PMID- 17522651
TI  - Scientific activism: signing on.

PMID- 17522652
TI  - Bright idea to improve prose but remain accurate.

PMID- 17522653
TI  - Endowments are necessary for museums to thrive.

PMID- 17522654
TI  - Look at biological systems through an engineer's eyes.

PMID- 17522655
TI  - Laying solid foundations for Europe.

PMID- 17522660
TI  - Oceanography: power of pull.

PMID- 17522661
TI  - Laser technology: less excitement for more gain.

PMID- 17522662
TI  - Circadian rhythms: metabolic clockwork.

PMID- 17522663
TI  - Biophysics: bending over to attract.

PMID- 17522664
TI  - Molecular medicine: microRNAs and the tell-tale heart.

PMID- 17522665
TI  - Condensed-matter physics: a superfluid is born.

PMID- 17522667
TI  - Molecular biology: RNA in control.

PMID- 17522668
TI  - Hydrology: flood of data.

PMID- 17522669
TI  - Supernovae: answers and questions.

PMID- 17522671
TI  - Perceptions of epigenetics.
AB  - Geneticists study the gene; however, for epigeneticists, there is no obvious
      'epigene'. Nevertheless, during the past year, more than 2,500 articles, numerous
      scientific meetings and a new journal were devoted to the subject of epigenetics.
      It encompasses some of the most exciting contemporary biology and is portrayed by
      the popular press as a revolutionary new science--an antidote to the idea that we
      are hard-wired by our genes. So what is epigenetics?

PMID- 17522672
TI  - Transcription and RNA interference in the formation of heterochromatin.
AB  - Transcription in heterochromatin seems to be an oxymoron--surely the 'silenced'
      form of chromatin should not be transcribed. But there have been frequent reports
      of low-level transcription in heterochromatic regions, and several hundred genes
      are found in these regions in Drosophila. Most strikingly, recent investigations
      implicate RNA interference mechanisms in targeting and maintaining
      heterochromatin, and these mechanisms are inherently dependent on transcription.
      Silencing of chromatin might involve trans-acting sources of the crucial small
      RNAs that carry out RNA interference, but in some cases, transcription of the
      region to be silenced seems to be required--an apparent contradiction.

PMID- 17522673
TI  - The complex language of chromatin regulation during transcription.
AB  - An important development in understanding the influence of chromatin on gene
      regulation has been the finding that DNA methylation and histone post
      translational modifications lead to the recruitment of protein complexes that
      regulate transcription. Early interpretations of this phenomenon involved gene
      regulation reflecting predictive activating or repressing types of modification.
      However, further exploration reveals that transcription occurs against a backdrop
      of mixtures of complex modifications, which probably have several roles. Although
      such modifications were initially thought to be a simple code, a more likely
      model is of a sophisticated, nuanced chromatin 'language' in which different
      combinations of basic building blocks yield dynamic functional outcomes.

PMID- 17522674
TI  - Nuclear organization of the genome and the potential for gene regulation.
AB  - Much work has been published on the cis-regulatory elements that affect gene
      function locally, as well as on the biochemistry of the transcription factors and
      chromatin- and histone-modifying complexes that influence gene expression.
      However, surprisingly little information is available about how these components
      are organized within the three-dimensional space of the nucleus. Technological
      advances are now helping to identify the spatial relationships and interactions
      of genes and regulatory elements in the nucleus and are revealing an unexpectedly
      extensive network of communication within and between chromosomes. A crucial
      unresolved issue is the extent to which this organization affects gene function,
      rather than just reflecting it.

PMID- 17522675
TI  - Epigenetic inheritance in plants.
AB  - The function of plant genomes depends on chromatin marks such as the methylation
      of DNA and the post-translational modification of histones. Techniques for
      studying model plants such as Arabidopsis thaliana have enabled researchers to
      begin to uncover the pathways that establish and maintain chromatin
      modifications, and genomic studies are allowing the mapping of modifications such
      as DNA methylation on a genome-wide scale. Small RNAs seem to be important in
      determining the distribution of chromatin modifications, and RNA might also
      underlie the complex epigenetic interactions that occur between homologous
      sequences. Plants use these epigenetic silencing mechanisms extensively to
      control development and parent-of-origin imprinted gene expression.

PMID- 17522676
TI  - Stability and flexibility of epigenetic gene regulation in mammalian development.
AB  - During development, cells start in a pluripotent state, from which they can
      differentiate into many cell types, and progressively develop a narrower
      potential. Their gene-expression programmes become more defined, restricted and,
      potentially, 'locked in'. Pluripotent stem cells express genes that encode a set
      of core transcription factors, while genes that are required later in development
      are repressed by histone marks, which confer short-term, and therefore flexible,
      epigenetic silencing. By contrast, the methylation of DNA confers long-term
      epigenetic silencing of particular sequences--transposons, imprinted genes and
      pluripotency-associated genes--in somatic cells. Long-term silencing can be
      reprogrammed by demethylation of DNA, and this process might involve DNA repair.
      It is not known whether any of the epigenetic marks has a primary role in
      determining cell and lineage commitment during development.

PMID- 17522677
TI  - Phenotypic plasticity and the epigenetics of human disease.
AB  - It is becoming clear that epigenetic changes are involved in human disease as
      well as during normal development. A unifying theme of disease epigenetics is
      defects in phenotypic plasticity--cells' ability to change their behaviour in
      response to internal or external environmental cues. This model proposes that
      hereditary disorders of the epigenetic apparatus lead to developmental defects,
      that cancer epigenetics involves disruption of the stem-cell programme, and that
      common diseases with late-onset phenotypes involve interactions between the
      epigenome, the genome and the environment. Increased understanding of epigenetic
      disease mechanisms could lead to disease-risk stratification for targeted
      intervention and to targeted therapies.

PMID- 17522678
TI  - Single-exciton optical gain in semiconductor nanocrystals.
AB  - Nanocrystal quantum dots have favourable light-emitting properties. They show
      photoluminescence with high quantum yields, and their emission colours depend on
      the nanocrystal size--owing to the quantum-confinement effect--and are therefore
      tunable. However, nanocrystals are difficult to use in optical amplification and
      lasing. Because of an almost exact balance between absorption and stimulated
      emission in nanoparticles excited with single electron-hole pairs (excitons),
      optical gain can only occur in nanocrystals that contain at least two excitons. A
      complication associated with this multiexcitonic nature of light amplification is
      fast optical-gain decay induced by non-radiative Auger recombination, a process
      in which one exciton recombines by transferring its energy to another. Here we
      demonstrate a practical approach for obtaining optical gain in the single-exciton
      regime that eliminates the problem of Auger decay. Specifically, we develop
      core/shell hetero-nanocrystals engineered in such a way as to spatially separate
      electrons and holes between the core and the shell (type-II heterostructures).
      The resulting imbalance between negative and positive charges produces a strong
      local electric field, which induces a giant ( approximately 100 meV or greater)
      transient Stark shift of the absorption spectrum with respect to the luminescence
      line of singly excited nanocrystals. This effect breaks the exact balance between
      absorption and stimulated emission, and allows us to demonstrate optical
      amplification due to single excitons.

PMID- 17522679
TI  - An unusually brilliant transient in the galaxy M85.
AB  - Historically, variable and transient sources have both surprised astronomers and
      provided new views of the heavens. Here we report the discovery of an optical
      transient in the outskirts of the lenticular galaxy Messier 85 in the Virgo
      cluster. With a peak absolute R magnitude of -12, this event is distinctly
      brighter than novae, but fainter than type Ia supernovae (which are expected in a
      population of old stars in lenticular galaxies). Archival images of the field do
      not show a luminous star at that position with an upper limit in the g filter of
      about -4.1 mag, so it is unlikely to be a giant eruption from a luminous blue
      variable star. Over a two-month period, the transient source emitted radiation
      energy of almost 10(47) erg and subsequently faded in the optical sky. It is
      similar to, but six times more luminous at peak than, an enigmatic transient in
      the galaxy M31 (ref. 1). A possible origin of M85 OT2006-1 is a stellar merger.
      If so, searches for similar events in nearby galaxies will not only allow study
      of the physics of hyper-Eddington sources, but also probe an important phase in
      the evolution of stellar binary systems.

PMID- 17522680
TI  - Aggregation and vesiculation of membrane proteins by curvature-mediated
      interactions.
AB  - Membrane remodelling plays an important role in cellular tasks such as
      endocytosis, vesiculation and protein sorting, and in the biogenesis of
      organelles such as the endoplasmic reticulum or the Golgi apparatus. It is well
      established that the remodelling process is aided by specialized proteins that
      can sense as well as create membrane curvature, and trigger tubulation when added
      to synthetic liposomes. Because the energy needed for such large-scale changes in
      membrane geometry significantly exceeds the binding energy between individual
      proteins and between protein and membrane, cooperative action is essential. It
      has recently been suggested that curvature-mediated attractive interactions could
      aid cooperation and complement the effects of specific binding events on membrane
      remodelling. But it is difficult to experimentally isolate curvature-mediated
      interactions from direct attractions between proteins. Moreover, approximate
      theories predict repulsion between isotropically curving proteins. Here we use
      coarse-grained membrane simulations to show that curvature-inducing model
      proteins adsorbed on lipid bilayer membranes can experience attractive
      interactions that arise purely as a result of membrane curvature. We find that
      once a minimal local bending is realized, the effect robustly drives protein
      cluster formation and subsequent transformation into vesicles with radii that
      correlate with the local curvature imprint. Owing to its universal nature,
      curvature-mediated attraction can operate even between proteins lacking any
      specific interactions, such as newly synthesized and still immature membrane
      proteins in the endoplasmic reticulum.

PMID- 17522681
TI  - Intense hurricane activity over the past 5,000 years controlled by El Nino and
      the West African monsoon.
AB  - The processes that control the formation, intensity and track of hurricanes are
      poorly understood. It has been proposed that an increase in sea surface
      temperatures caused by anthropogenic climate change has led to an increase in the
      frequency of intense tropical cyclones, but this proposal has been challenged on
      the basis that the instrumental record is too short and unreliable to reveal
      trends in intense tropical cyclone activity. Storm-induced deposits preserved in
      the sediments of coastal lagoons offer the opportunity to study the links between
      climatic conditions and hurricane activity on longer timescales, because they
      provide centennial- to millennial-scale records of past hurricane landfalls. Here
      we present a record of intense hurricane activity in the western North Atlantic
      Ocean over the past 5,000 years based on sediment cores from a Caribbean lagoon
      that contain coarse-grained deposits associated with intense hurricane landfalls.
      The record indicates that the frequency of intense hurricane landfalls has varied
      on centennial to millennial scales over this interval. Comparison of the sediment
      record with palaeo-climate records indicates that this variability was probably
      modulated by atmospheric dynamics associated with variations in the El
      Nino/Southern Oscillation and the strength of the West African monsoon, and
      suggests that sea surface temperatures as high as at present are not necessary to
      support intervals of frequent intense hurricanes. To accurately predict changes
      in intense hurricane activity, it is therefore important to understand how the El
      Nino/Southern Oscillation and the West African monsoon will respond to future
      climate change.

PMID- 17522682
TI  - Evolution of cooperation in a finite homogeneous graph.
AB  - Recent theoretical studies of selection in finite structured populations have
      worked with one of two measures of selective advantage of an allele: fixation
      probability and inclusive fitness. Each approach has its own analytical
      strengths, but given certain assumptions they provide equivalent results. In most
      instances the structure of the population can be specified by a network of nodes
      connected by edges (that is, a graph), and much of the work here has focused on a
      continuous-time model of evolution, first described by ref. 11. Working in this
      context, we provide an inclusive fitness analysis to derive a surprisingly simple
      analytical condition for the selective advantage of a cooperative allele in any
      graph for which the structure satisfies a general symmetry condition ('bi
      transitivity'). Our results hold for a broad class of population structures,
      including most of those analysed previously, as well as some for which a direct
      calculation of fixation probability has appeared intractable. Notably, under some
      forms of population regulation, the ability of a cooperative allele to invade is
      seen to be independent of the nature of population structure (and in particular
      of how game partnerships are specified) and is identical to that for an
      unstructured population. For other types of population regulation our results
      reveal that cooperation can invade if players choose partners along relatively
      'high-weight' edges.

PMID- 17522684
TI  - Forceps delivery: potential benefits and a call for continued training.

PMID- 17522683
TI  - An autopodial-like pattern of Hox expression in the fins of a basal
      actinopterygian fish.
AB  - Comparative analyses of Hox gene expression and regulation in teleost fish and
      tetrapods support the long-entrenched notion that the distal region of tetrapod
      limbs, containing the wrist, ankle and digits, is an evolutionary novelty. Data
      from fossils support the notion that the unique features of tetrapod limbs were
      assembled over evolutionary time in the paired fins of fish. The challenge in
      linking developmental and palaeontological approaches has been that developmental
      data for fins and limbs compare only highly derived teleosts and tetrapods; what
      is lacking are data from extant taxa that retain greater portions of the fin
      skeletal morphology considered primitive to all bony fish. Here, we report on the
      expression and function of genes implicated in the origin of the autopod in a
      basal actinopterygian, Polyodon spathula. Polyodon exhibits a late-phase,
      inverted collinear expression of 5' HoxD genes, a pattern of expression long
      considered a developmental hallmark of the autopod and shown in tetrapods to be
      controlled by a 'digit enhancer' region. These data show that aspects of the
      development of the autopod are primitive to tetrapods and that the origin of
      digits entailed the redeployment of ancient patterns of gene activity.

PMID- 17522685
TI  - Old school.
AB  - In the last decade, the American Board of Pediatrics has reduced the number of
      required intensive care rotations. The Accreditation Council for Graduate Medical
      Education has established guidelines that limit on-call nights to 24 h and the
      work week to 80 h. This has had a positive impact on housestaff training and
      patient safety. Inadequate experience can reduce proficiency, especially in the
      acute management of a sick newborn. New guidelines and evidence-based standards
      need to assure competency without compromising work hours and broad-based
      exposure. Times change, but the passion and privilege of caring for sick newborns
      does not.

PMID- 17522686
TI  - Imaging case book. Oropharyngeal neuroglial choristoma.

PMID- 17522687
TI  - Premature twins of a mother with Graves' disease with discordant thyroid
      function: a case report.
AB  - Thyroid dysfunction is recognized in the newborns of mothers affected by Graves'
      disease during pregnancy. We describe the development of concurrent
      hyperthyroidism and hypothyroidism in the twin infants of a mother with Graves'
      disease diagnosed during pregnancy.

PMID- 17522688
TI  - Case report: perianal necrotizing fasciitis in a near-term neonate.
AB  - Necrotizing fasciitis in the neonatal period is a rare, life-threatening
      condition. Previous cases of neonatal necrotizing fasciitis in the perianal
      region were speculated to have been initiated by rectal mucosal trauma secondary
      to rectal temperature measurements. We observed a case of fatal perianal
      necrotizing fasciitis in a neonate where the process began as a red ring
      surrounding the anus and guiac-positive stools, detected after a rectal
      temperature measurement. We speculate that the perianal necrotizing fasciitis
      that subsequently developed might have been initiated by a minor rectal mucosal
      injury, and we investigated the instrument used for the rectal temperature
      measurement to assess any potential areas on the probe sheath cover that might
      cause a minor injury. Each probe sheath cover examined had three areas that, in
      our opinion, could possibly generate a minor mucosal injury.

PMID- 17522689
TI  - Endogenous group B streptococcal endophthalmitis in a preterm infant.
AB  - Endogenous endophthalmitis is a rare complication of bacteremia. Proper
      intervention is critical, as the majority of affected patients lose vision in the
      infected eye. Treatment options include systemic antibiotics, intravitreous
      antibiotics and vitrectomy. We report a case of endogenous endophthalmitis
      presenting as leukocoria in a premature neonate with group B streptococcal
      meningitis.

PMID- 17522690
TI  - COX inhibition for tocolysis and its effect on the neonate.

PMID- 17522693
TI  - Genotype and phenotype correlation of calcium-sensing receptor variants.
AB  - Mutations of the calcium-sensing receptor (CaR) gene give rise to disorders of
      renal calcium excretion. It is now demonstrated that even common variants of CaR
      can cause alteration in tissue sensitivity to extracellular calcium and are
      associated with primary hypercalciuria. Agents targeting these functional domains
      may well be an option for the management of hypercalciuria and renal stones.

PMID- 17522694
TI  - A new cross-talk pathway between the renal tubule and its own glomerulus.
AB  - The connecting tubule (CNT) of superficial nephrons comes into close contact with
      the corresponding afferent arteriole of its own glomerulus. Ren et al.
      demonstrate that this close anatomical configuration is also the site for cross
      talk between the CNT and the afferent arteriole. This mechanism is triggered by
      the entry of sodium through amiloride sodium channels and may antagonize
      tubuloglomerular feedback.

PMID- 17522695
TI  - Underglycosylation of IgA in IgA nephropathy: more than a diagnostic marker?
AB  - Moldoveanu et al. present a diagnostic test for IgA nephropathy based on the
      presence of undergalactosylated IgA in serum. This underglycosylated IgA appears
      to be overrepresented in serum of IgA nephropathy patients and is most likely
      related to mesangial IgA deposition. Further studies on the nature, production,
      regulation, and cellular and molecular interactions of this undergalactosylated
      IgA may facilitate disease diagnosis and provide further insight into the
      pathogenesis of this important disease.

PMID- 17522697
TI  - Plagiarism.

PMID- 17522698
TI  - Impact of new dialysis solutions on peritonitis rates.

PMID- 17522699
TI  - Acute renal failure in a patient with paroxysmal nocturnal hemoglobinuria.

PMID- 17522700
TI  - Renal radiation-induced arterial stenosis.

PMID- 17522702
TI  - Absence of senescence-associated beta-galactosidase activity in human melanocytic
      nevi in vivo.

PMID- 17522703
TI  - Impaired PI3K/Akt activation-mediated NF-kappaB inactivation under elevated TNF
      alpha is more vulnerable to apoptosis in vitiliginous keratinocytes.
AB  - Levels of the cytokines IL-6, IL-1alpha, and tumor necrosis factor-alpha (TNF
      alpha) are significantly higher in lesional than in non-lesional skin of patients
      with vitiligo. However, how cytokines affect pigmentation is not fully
      understood. To examine the mechanism, Western blot analysis with TNF-alpha, Fas
      ligand (FasL), and downstream signaling molecules such as I-kappaB, NF-kappaB,
      TNF-R1-associated factor 2, Akt, and PTEN (phosphatase and tension homologue)
      were performed for the suction-blistered depigmented and normally pigmented
      epidermis from 10 patients. Levels of TNF-alpha and FasL were significantly
      higher in the depigmented epidermis. Interestingly, phosphorylation levels of I
      kappaB, NF-kappaB, and Akt were lower in the depigmented epidermis. Moreover,
      PTEN, which could inhibit the phosphatidylinositol 3-kinase/protein kinase B
      (PI3K/Akt) signaling pathway, was significantly higher in depigmented epidermis,
      implying that vitiliginous keratinocytes may be more susceptible to TNF-alpha
      mediated apoptosis through impaired Akt and NF-kappaB activation. To test this
      hypothesis, cultured normal human keratinocytes were treated with TNF-alpha in
      the presence of a PI3K inhibitor to suppress Akt activation. Keratinocytes
      showing impaired Akt activation demonstrated increased apoptosis with less
      activation of NF-kappaB. Thus, reduced activation of NF-kappaB via impaired
      PI3K/Akt activation under increased TNF-alpha levels could result in increased
      apoptosis of vitiliginous keratinocytes.

PMID- 17522705
TI  - Trends in nonmelanoma skin cancer mortality rates in the United States, 1969
      through 2000.
AB  - The purpose of this population-based study was to assess trends in mortality
      rates for nonmelanoma skin cancer (NMSC) in the United States. Particular
      emphasis was placed on the subgroup of malignancies arising on genital skin.
      Nearly 75,000 deaths in the United States were attributed to NMSC from 1969 to
      2000. The age-adjusted US mortality rate for NMSC arising on nongenital skin from
      1969 to 2000 was 0.69/10(5)/year; the rate among men was twice that among women.
      Mortality rates among white men exceeded that of black men by a factor of two;
      the same was observed among women, but by a smaller multiple. Corresponding
      mortality rates for malignancies arising from genital skin (penis, scrotum,
      vulva) were higher in women (0.54) than in men (0.30). In contrast to nongenital
      NMSC, mortality rates among black men were twice that of white men; however,
      rates for white and black women were similar. These results suggest that greater
      emphasis could be placed on reducing mortality from genital NMSC while continuing
      to stress reduction of excess sun exposure.

PMID- 17522706
TI  - Quantification of inducible SOS-like photoprotective responses in human skin.
AB  - To document and quantify inducible photoprotective effects in human skin, explant
      cultures were treated once with thymidine dinucleotide (pTT) or diluent alone or
      UV-irradiated. Both pTT and UV increased the melanogenic protein levels on days 1
      5 and comparably increased melanocyte dendricity and epidermal melanin content.
      Explants treated with pTT or UV but not with diluent alone showed initial
      inhibition of epidermal proliferation followed by mild reactive hyperplasia;
      melanocyte proliferation was minimal. To determine whether pTT and UV provide
      comparable protection against subsequent UV-induced DNA damage, explants were pTT
      or diluent-treated or UV-irradiated. All explants were then irradiated with the
      same UV dose 72 hours later. Compared to diluent alone, pTT or UV pretreatment
      decreased the number of epidermal cells positive for cyclobutane pyrimidine
      dimers (CPDs) 50% immediately post-irradiation. In pTT- and UV- versus diluent
      pretreated explants, the rate of CPD removal was also more rapid, approximately
      80 vs 45% of the initial burden within 72 hours. These data confirm and quantify
      comparable SOS-like responses in human skin after pTT or UV irradiation,
      attributable to both increased epidermal melanin and increased DNA repair rate,
      in the case of pTT in the absence of initial damage.

PMID- 17522707
TI  - Two-color lymphatic mapping using Ig-conjugated near infrared optical probes.
AB  - To map the drainage patterns of the lymphatic system, multicolor optical probes
      must be developed, which can be interstitially administered. These agents must be
      of sufficient size to be retained by the lymphatic system and permit the
      conjugation or incorporation of fluorescent probes with varying emission
      wavelengths. Quantum dots fulfill these criteria, but their potential toxicity
      limits their application to research settings. Here, we describe the synthesis of
      lymphatic optical probes based on Igs conjugated with Cy5.5 and Cy7 and
      demonstrate in animal models that these agents can map the lymphatic drainage
      patterns within axillary nodes draining both the breast and upper extremity,
      cervical nodes draining both the ear and upper extremity, and sentinel lymph
      nodes draining different anatomic locations. The ability to separately and
      simultaneously visualize the drainage patterns from two separate lymphatic
      vessels may have implications for the preoperative mapping of lymph nodes before
      lymph node resection. The biocompatibility of fluorescently labeled Igs in
      comparison to other nanoparticulate fluorophores improves the chances of clinical
      translation. This noninvasive and biocompatible multicolor method of optical
      lymphangiography may elucidate the complex human lymphatic system and reduce the
      risk of lymphedema after surgery for melanoma and other cancers.

PMID- 17522708
TI  - Delivery and inhibition of reporter genes by small interfering RNAs in a mouse
      skin model.
AB  - RNA interference offers the potential of a novel therapeutic approach for
      treating skin disorders. To this end, we investigated delivery of nucleic acids,
      including a plasmid expressing the reporter gene luciferase, to mouse skin by
      intradermal injection into footpads using in vivo bioluminescence imaging over
      multiple time points. In order to evaluate the ability of RNA interference to
      inhibit skin gene expression, reporter gene constructs were co-injected with
      specific or non-specific siRNAs and the in vivo effects measured. Our results
      revealed that specific unmodified and modified siRNAs (but not nonspecific
      matched controls) strongly inhibit reporter gene expression in mice. These
      results indicate that small interfering RNA, delivered locally as RNA directly or
      expressed from viral or non-viral vectors, may be effective agents for treating
      skin disorders.

PMID- 17522710
TI  - Human adrenergic alpha 2A receptor C-1291G polymorphism leads to higher
      consumption of sweet food products.

PMID- 17522711
TI  - Converging evidence for a pseudoautosomal cytokine receptor gene locus in
      schizophrenia.
AB  - Schizophrenia is a strongly heritable disorder, and identification of potential
      candidate genes has accelerated in recent years. Genomewide scans have identified
      multiple large linkage regions across the genome, with fine-mapping studies and
      other investigations of biologically plausible targets demonstrating several
      promising candidate genes of modest effect. The recent introduction of
      technological platforms for whole-genome association (WGA) studies can provide an
      opportunity to rapidly identify novel targets, although no WGA studies have been
      reported in the psychiatric literature to date. We report results of a case
      control WGA study in schizophrenia, examining approximately 500 000 markers,
      which revealed a strong effect (P=3.7 x 10(-7)) of a novel locus (rs4129148) near
      the CSF2RA (colony stimulating factor, receptor 2 alpha) gene in the
      pseudoautosomal region. Sequencing of CSF2RA and its neighbor, IL3RA (interleukin
      3 receptor alpha) in an independent case-control cohort revealed both common
      intronic haplotypes and several novel, rare missense variants associated with
      schizophrenia. The presence of cytokine receptor abnormalities in schizophrenia
      may help explain prior epidemiologic data relating the risk for this illness to
      altered rates of autoimmune disorders, prenatal infection and familial leukemia.

PMID- 17522713
TI  - Chronic myeloid leukaemia as a model of disease evolution in human cancer.
AB  - Chronic myeloid leukaemia (CML) can be considered as a paradigm for neoplasias
      that evolve through a multi-step process. CML is also one of the best examples of
      a disease that can be targeted by molecular therapy; however, the success of new
      'designer drugs' is largely restricted to the chronic phase of the disease. If
      not cured at this stage, CML invariably progresses and transforms into an acute
      type leukaemia undergoing a 'blast crisis'. The causes of this transformation are
      still poorly understood. What mechanisms underlie this progression, and are they
      shared by other common cancers?

PMID- 17522712
TI  - The cofilin pathway in breast cancer invasion and metastasis.
AB  - Recent evidence indicates that metastatic capacity is an inherent feature of
      breast tumours and not a rare, late acquired event. This has led to new models of
      metastasis. The interpretation of expression-profiling data in the context of
      these new models has identified the cofilin pathway as a major determinant of
      metastasis. Recent studies indicate that the overall activity of the cofilin
      pathway, and not that of any single gene within the pathway, determines the
      invasive and metastatic phenotype of tumour cells. These results predict that
      inhibitors directed at the output of the cofilin pathway will have therapeutic
      benefit in combating metastasis.

PMID- 17522714
TI  - Nuclear microenvironments in biological control and cancer.
AB  - Nucleic acids and regulatory proteins are compartmentalized in microenvironments
      within the nucleus. This subnuclear organization may support convergence and the
      integration of physiological signals for the combinatorial control of gene
      expression, DNA replication and repair. Nuclear organization is modified in many
      cancers. There are cancer-related changes in the composition, organization and
      assembly of regulatory complexes at intranuclear sites. Mechanistic insights into
      the temporal and spatial organization of machinery for gene expression within the
      nucleus, which is compromised in tumours, provide a novel platform for diagnosis
      and therapy.

PMID- 17522715
TI  - Morphogens, morphostats, microarchitecture and malignancy.
AB  - Morphogenetic fields organize tissue morphology in the embryo. By analogy,
      morphostatic fields maintain normal cell behaviour and normal tissue
      microarchitecture in the adult. The most prominent feature of cancer is the
      disruption of tissue microarchitecture. Cancer occurs much more frequently when
      morphostatic influences fail (metaplasia) or at the junction of two different
      morphostatic fields. This Review will describe what we know about morphostats and
      morphostasis, discuss the evidence for the role of disruption of morphostasis in
      malignancy, and address some testable hypotheses.

PMID- 17522716
TI  - Possible molecular mechanisms involved in the toxicity of angiogenesis
      inhibition.
AB  - Contrary to initial expectations, angiogenesis inhibitors can cause toxicities in
      patients with cancer. The toxicity profiles of these inhibitors reflect the
      disturbance of growth factor signalling pathways that are important for
      maintaining homeostasis. Experiences with angiogenesis inhibitors in clinical
      trials indicate that short-term toxicities are mostly manageable. However, these
      agents will also be given in prolonged treatment strategies, so we need to
      anticipate possible long-term toxicities. In addition, understanding the
      molecular mechanisms involved in the toxicity of angiogenesis inhibition should
      allow more specific and more potent inhibitors to be developed.

PMID- 17522717
TI  - Millennium development goals: an unbalanced approach to global health.

PMID- 17522718
TI  - CRP has little incremental value over traditional cardiovascular risk factors in
      risk stratification.

PMID- 17522719
TI  - Programmed ventricular stimulation for risk stratification in patients with
      tetralogy of Fallot: a Bayesian perspective.

PMID- 17522720
TI  - Evaluation and management of transient ischemic attack: an important component of
      stroke prevention.
AB  - Stroke and transient ischemic attack (TIA) share similar risk factors and methods
      of evaluation and secondary prevention. As neurological symptoms resolve after
      TIA, however, there has been a widely held perception that urgent evaluation and
      treatment following TIA are unnecessary. In actual fact, it is becoming
      increasingly clear that the short-term stroke risk after TIA is very high. Recent
      studies have identified independent predictors that indicate which patients are
      at highest risk of recurrent ischemic events. These risk scores could enable
      physicians to target appropriate patients for urgent care. In this Review, we
      summarize the recent literature on stroke risk after TIA and risk stratification,
      and recently published guidelines on evaluation and treatment.

PMID- 17522721
TI  - Pulmonary arterial hypertension: current therapeutic strategies.
AB  - The treatment of pulmonary arterial hypertension--once a lethal condition--has
      evolved considerably over the past few years as the number of therapeutic options
      available to treat this disease has increased. In this Review we attempt to
      summarize the current knowledge of the pathogenesis of pulmonary hypertension, in
      relation to the therapies presently available and those that could become
      available in the near future. The use of prostacyclin and its analogs, calcium
      channel blockers, endothelin-receptor antagonists and phosphodiesterase type 5
      inhibitors is reviewed. Newer concepts, such as the use of combination therapy,
      and the potential for long-term disease amelioration and improvement of outcomes,
      are also discussed. The role of supportive care and medications not specific to
      pulmonary hypertension is also examined. In addition, we review the novel
      emerging therapies, such as imatinib, fasudil, simvastatin, ghrelin and
      vasoactive intestinal peptide, which hold therapeutic potential for disease
      modification as well as treatment of symptoms.

PMID- 17522722
TI  - Surgery insight: the dilated ascending aorta--indications for surgical
      intervention.
AB  - Awareness of the clinical significance of thoracic aortic aneurismal disease has
      increased in recent years. As diagnostic tools have improved our ability to
      identify aortic pathology, surgical outcomes have also improved, making
      intervention a life-saving option in the majority of cases. Here, we aim to
      examine the indications for surgical intervention on the dilated aorta,
      particularly the ascending segment. Studies of the natural history of ascending
      aortic aneurysms indicate that aneurysms exceeding 6 cm in maximum diameter are
      associated with a particularly high risk of complications. In the interest of
      providing some margin of safety, most surgeons would agree that intervention is
      indicated with an aortic diameter of 5.5 cm. Many would intervene even earlier
      (at 5.0 cm) for patients at low surgical risk, or for those with known connective
      tissue disorders such as Marfan's syndrome. In some cases, only the ascending
      aortic segment needs to be treated, while in others full root replacement is
      required. Reduction aortoplasty has been superseded largely by interposition
      graft replacement. The standard procedure involves replacement of the valve and
      root with a composite mechanical conduit or tissue root prosthesis, and results
      are excellent. Recently developed valve-sparing root reconstructive options,
      however, are promising and have encouraged an even more aggressive surgical
      stance.

PMID- 17522723
TI  - Native triple-valve endocarditis caused by penicillin-resistant Streptococcus
      sanguis.
AB  - BACKGROUND: A 26-year-old man with known but untreated ventricular septal defect
      was admitted to the emergency ward with abdominal pain, fever and weight loss.
      Transthoracic echocardiography showed multiple vegetations on the anterior mitral
      leaflet, a mobile vegetation on the surface of the aortic noncoronary cusp and
      another on the tricuspid valve. His blood cultures grew Streptococcus sanguis
      with a penicillin minimum inhibitory concentration of 3 microg/ml.
      INVESTIGATIONS: Physical examination, echocardiography, blood cultures, minimal
      inhibitory concentration detection. DIAGNOSIS: Multivalvular infective
      endocarditis caused by S. sanguis with a high penicillin resistance. MANAGEMENT:
      A combination of intravenous vancomycin and gentamicin, followed by early
      surgery.

PMID- 17522724
TI  - Fellowship awards presented at the 2006 annual general conference at ho.

PMID- 17522725
TI  - Cryopreservation of embryogenic tissues of Pinus nigra Arn. by a slow freezing
      method.
AB  - Six different embryogenic cell lines of Pinus nigra Arn. have been cryopreserved
      in liquid nitrogen using cryoprotection with sucrose (18%) and DMSO (7.5%). Post
      thaw growth and tissue proliferation have been observed in five cell lines. The
      survival levels after storage in liquid nitrogen reached values between 62.5 and
      100%. Growth of recovered embryogenic cells as well as somatic embryos is similar
      to the non-frozen tissues maintained in long-term culture. Somatic embryo
      maturation and plantlet regeneration occurred in all selected cell lines.

PMID- 17522726
TI  - Larch (Larix kaempferi) xylem parenchyma cells respond to subfreezing temperature
      by deep supercooling.
AB  - In previous studies, xylem parenchyma cells (XPCs) in the boreal softwood species
      larch, which has thick and rigid walls similar to those of XPCs in boreal
      hardwood species, were shown to respond to subfreezing temperature by deep
      supercooling during summer but change their freezing behavior to extracellular
      freezing during winter. In this study, we re-examined freezing behavior of XPCs
      in larch by observation of deep etching of frozen samples as well as observation
      of re-warmed samples after freezing using a cryo-scanning electron microscope.
      The results showed that XPCs in larch adapts to subfreezing temperature by deep
      supercooling throughout all seasons. Such freezing behavior is the same as that
      of XPCs in boreal hardwood species.

PMID- 17522727
TI  - Cryopreservation of Pistacia spp. seeds by dehydration and one-step freezing.
AB  - Cryopreservation protocols by dehydration and one-step freezing were developed
      for seeds from three Pistacia species, i.e., P. vera, P. terebinthus and P.
      lentiscus, which were characterised by different initial germination percentages
      (100%, 17% and 81%, respectively). In P. vera, a maximum of 90% germination was
      obtained following 8 hours drying in silica gel (corresponding to 11.7% moisture
      content on a FW basis) and direct immersion in LN. In P. terebinthus and P.
      lentiscus, shorter periods of dehydration (1 hour and 15 min, respectively) were
      sufficient to reduce their moisture content to about 20%, which resulted in peak
      seed germination percentages from cryostorage of 16% and 47%, respectively.
      Following cryopreservation, the seeds germinated better on semi-solid MS medium,
      than on cotton wool wetted with dH(2)O or liquid MS medium. Finally, in P. vera
      and P. lentiscus, high and significant correlation coefficients were obtained
      between the TTC viability test and seed germinability after recovery from LN,
      provided that seeds which were considered positive in the test showed completely
      or partially red embryonic axes coupled to completely red cotyledons.

PMID- 17522728
TI  - Intracellular sugars improve survival of human red blood cells cryopreserved at 
      80 degrees C in the presence of polyvinyl pyrrolidone and human serum albumin.
AB  - Cryopreservation with impermeable protectants has great significance on storage
      of human red blood cells. It has become feasible to use glycerol free
      cryopreservation for human red blood cells. This study focuses on the effect of
      intracellular trehalose or glucose on human red blood cells cryopreserved in the
      presence of polymer. Red blood cells were cryopreserved for 48 h-72 h at -80
      degrees C. The data showed that the loading efficiency of glucose was
      significantly higher than that of trehalose, but trehalose loading process
      induced more hemolysis than glucose loading process. Compared with the other
      groups, the combination of intracellular glucose, PVP, and human serum albumin
      can significantly decrease the percent hemolysis after cryopreservation (P<0.01).
      However, the percent hemolysis induced by intracellular trehalose was less than
      that induced by extracellular trehalose, but the difference was not significant
      (P<0.05). The adenosine 5'-triphosphate (ATP) level and 2,3-diphosphoglycerate
      (2,3-DPG) level of cryopreserved red blood cells were significantly less than
      those of fresh red blood cells. However, sugars can provide certain protection
      for ATP and 2, 3-DPG compared with red blood cells cryopreserved in the absence
      of sugars. The protection of glucose on the metabolic function was more than that
      of trehalose. Cryopreservation can increase the percentage of cells with exposed
      phosphatidylserine (PS), but the ability of trehalose to maintain PS normal
      distribution is higher than that of glucose. Furthermore, intracellular sugars
      can protect membrane integrity of cryopreserved red blood cells, although a small
      portion of cells appeared spherocytic or echinocytic shape. Finally, most
      membrane proteins of cryopreserved red blood cells were similar to the membrane
      proteins of fresh red blood cells, but trehalose can result in loss of
      glyceraldehyde phosphate dehydrogenase (GAPD) and peroxiredoxin 2. In conclusion,
      it is feasible to cryopreserve red blood cells using polymer, human albumin and
      sugars as main protectants. The cryoprotective effect of glucose may be better
      than that of trehalose in the presence of PVP and human serum albumin, because
      sugar loading process causes more cell injuries in case of trehalose compared to
      glucose, and these injuries in turn manifest themselves during subsequent
      cryopreservation and thawing. In the future, finding an approach to decrease the
      injuries during trehalose loading process still is critical.

PMID- 17522729
TI  - Acquisition of cryotolerance in maize embryos during seed development.
AB  - A desiccation-based cryopreservation protocol was employed to study the
      development of cryotolerance and desiccation tolerance in maize embryos from 23
      to 50 days after pollination (DAP). Tolerances were acquired gradually and
      concomitantly. Maize embryos had low desiccation tolerance at 23 DAP when
      assessed by survival (embryo elongation) and emergence (root and shoot growth)
      after dehydration. Desiccation tolerance increased progressively, reached its
      maximum at 38 DAP, and remained constant afterwards. Cryotolerance, assessed by
      survival and emergence of post-thaw embryos, however, was nil until 26 DAP.
      Embryos at 29 DAP withstood cryoexposure within a very narrow moisture range
      only. Throughout development cryotolerance increased gradually, reached a maximum
      at 44 DAP and then remained at this level. The correlation between moisture
      content and cryopreservation success was notably influenced by the maize embryo's
      development stage. As seeds developed, the moisture content allowing 90%
      dehydrated embryos to survive and to emerge decreased, while the upper moisture
      content allowing 50% post-thaw embryos to survive and to emerge increased.
      Moisture contents of c. 14% allowed no less than 50% post-thaw embryos to emerge
      at the later development stages (e.g. c. 44 DAP); but no embryos within the same
      moisture range survived cryoexposure at 29 DAP, although they could withstand
      desiccation to this moisture level without impairment of survival and emergence.
      The relationship between cryotolerance and desiccation tolerance during maize
      seed development is discussed.

PMID- 17522730
TI  - New calorimetric system and some results of water phase transition research in
      plant roots.
AB  - The principle of operation and main parameters of the recently created scanning
      differential reverse microcalorimeter of the new generation are presented. The
      microcalorimeter is destined for studying water crystallization and ice melting
      processes in heterogeneous systems, including plant and animal cells and tissues
      in the temperature range of 20 to -55 degrees C. In order to obtain maximum
      information from the experimental results respective algorithms and applied
      software package were developed. The results of studies of water crystallization
      and ice melting processes in different parts of common plantain (Plantago major
      L.) root, as a certain model system, can give us information on the peculiarities
      of the studied processes in complex, heterogeneous systems.

PMID- 17522731
TI  - Effects of removal of necrotic blastomeres from human cryopreserved embryos on
      pregnancy outcome.
AB  - This study assessed whether the implantation potential of embryos that were
      partially damaged after freezing and thawing can be improved by removal of
      necrotic blastomeres. We retrospectively analyzed the pregnancy rate and
      implantation rate of 170 human frozen embryo transfer cycles. Laser-assisted
      hatching and micromanipulation were performed to remove the necrotic blastomeres.
      A higher clinical pregnancy rate (22.22%) and embryo implantation rate (10.17%)
      were observed when transferred embryos comprised fully intact and partially
      damaged embryos compared with partially damaged embryos alone (5.88% and 2.82%,
      respectively). When transferred embryos were fully intact and partially damaged
      embryos, removal of necrotic blastomeres from partially damaged embryos
      significantly increased the clinical pregnancy rate (43.90% versus 24.00%,
      P<0.05) and the implantation rate (19.44% versus 10.29%, P<0.05). The results
      indicated that the implantation potential of partially damaged cryopreserved
      embryos can be improved by removal of necrotic blastomeres with laser-assisted
      hatching and micromanipulation.

PMID- 17522732
TI  - [Modifiable cardiovascular risk factors in doctors and other health care
      professionals].

PMID- 17522733
TI  - [Contamination and public health in Mexico].

PMID- 17522734
TI  - [Barriers to accessing health care services for the indigenous population in
      Rabinal, Guatemala].
AB  - OBJECTIVE: To identify and document access barriers to health care services for
      the indigenous population in Rabinal, Guatemala. MATERIAL AND METHODS: A
      qualitative analysis was used. Over a period of two months, 20 semi-directional
      interviews were conducted in Rabinal, Guatemala: 15 with Achis indigenous people
      and five with health professionals. A focus group was done to verify the
      information collected during the individual interviews. The qualitative analysis
      was based on the transcription of interviews and the compilation of the data.
      RESULTS: Barriers to access are inter-relational. Geographic barriers include
      distance and a significant lack of means of transportation. Economic barriers are
      the cost of office visits and medicine. Among the cultural barriers, the Spanish
      language is an obstacle. Indigenous people have other concepts of medicine and
      treatments and they complain on occasion of abuse by health professionals. At the
      same time, health professionals recognize that the trauma of the civil war is
      still present and criticize the poor living conditions and the lack of resources.
      CONCLUSIONS: Health care services in Rabinal are inadequate and insufficient for
      responding to the needs of the local population.

PMID- 17522735
TI  - Prevalence of the metabolic syndrome and associated lifestyles in adult males
      from Oaxaca, Mexico.
AB  - OBJECTIVE: To determine the associations of metabolic syndrome (MS) with
      residential area and lifestyle in men from Oaxaca, Mexico. MATERIAL AND METHODS:
      A cross-sectional study was conducted in 1998 in 325 apparently healthy men 35 to
      65 years of age in four residential areas: rural, urban poor, urban middle, and
      urban rich. MS was defined according to International Diabetes Federation (IDF)
      guidelines. Information on physical activity and diet was collected by
      questionnaire. Based on two 24-hour recalls, a diet quality index (DQI) using
      eight WHO recommendations to prevent chronic diseases was constructed. RESULTS:
      The MS rate was 41.2%; twice as high in urban (45.4%) than rural (27.6%)
      subjects. A significantly higher risk of MS was associated with low DQI in urban
      poor (OR 2.5; CI: 1.0-6.3) and rich (OR 3.2; CI: 1.5-8.6), compared to rural
      subjects. Physical activity was an independent protective factor. CONCLUSIONS: MS
      is highly prevalent in apparently healthy men in urban areas, illustrating the
      role of diet and lifestyle transition.

PMID- 17522736
TI  - [Risk factors for dislypidemia in obese children and adolescents].
AB  - OBJECTIVE: To assess the risk of dislypidemia associated with obesity in children
      and adolescents. MATERIAL AND METHODS: A cross sectional study was conducted with
      62 obese children (BMI > 95 centile and tricipital skinfold thickness > 90
      centile) and 70 non-obese children (BMI 5-85 centile) ages 5-15 years, without
      chronic diseases. Subjects' characteristics and family background of chronic
      diseases were collected and a lipid profile was determined. The risk of lipid
      alterations in the obese children was calculated using odds ratio (OR) and
      multivariate analysis. RESULTS: Mean age was 9.8 +/- 2.7 years in both groups; 63
      girls and 69 boys were included. Obesity was associated with abnormal values for
      cholesterol, triglycerides, LDL, HDL and dislypidemia (> 1 abnormal value) (OR
      4.47-15.0). In obese children and adolescents the multivariate analysis showed
      that female gender was associated with dislypidemia. CONCLUSION: Obesity in
      children and adolescents is associated with high risk of dislypidemia; the risk
      is higher among females.

PMID- 17522737
TI  - [Psychosocial work factors associated to blood pressure and cardiovascular
      symptoms among Mexican nurses].
AB  - OBJECTIVE: To determine if job stress, according with Karasek's model, and job
      insecurity are significantly associated with cardiovascular indicators such as
      blood pressure (BP) and cardiovascular symptoms (CS), considering traditional
      risk factors for cardiovascular disease (age, body mass index, smoking, alcohol
      consumption, among others). MATERIAL AND METHODS: A job content questionnaire
      (JCQ) and one for cardiovascular symptoms were administered to a sample of 109
      nurses from a public hospital in Mexico City during July 2004. A digital monitor
      was utilized to measure BP at the workplace using a point estimates protocol.
      RESULTS: A significant association among these variables was found (beta between
      .20 and .24), even when traditional cardiovascular risk factors were considered.
      CONCLUSIONS: The relation between job stress and BP is significant in the Mexican
      population and highlights the association between job insecurity and
      cardiovascular indicators, indicating its importance in the Mexican work context.
      Future studies are suggested, as well as the prevention and surveillance of these
      factors in occupational and public health fields in terms of their role in
      cardiovascular epidemiology.

PMID- 17522738
TI  - [Trends in caesarean sections associated with non-clinical factors in a Birthing
      Educational Center in Mexico City].
AB  - OBJECTIVES: To describe the trends in caesarian sections (CS) associated with non
      clinical factors in women who attended a birthing educational facility, also
      known as 'Centro de Educacion,' (CEPAPAR) in Mexico City. METHODS: Data from 992
      births of 847 women that occurred from 1988-2000 were analyzed using linear
      regression to identify the association between non-clinical factors and time
      trends in CS. RESULTS: The overall incidence of CS was 32.8%, with an 8% average
      annual increase. Until 1994 the percentage of CS remained relatively steady at
      30%, increasing to 40% in subsequent years. In analyzing trends in CS and their
      relationship with non-clinical factors from 1988-2000, the increased incidence of
      CS during this period was higher among births where no birth attendant was
      present, for first-time mothers, and in larger hospitals (>50 beds). CONCLUSIONS:
      Results show that the increased incidence of CS is associated with non-clinical
      factors such as size of the hospital and the presence of a birth attendant. A
      model of support for women which includes information, counseling, and the
      presence of a birth attendant during labor can contribute to reducing the risk of
      unnecessary CS in populations such as that studied.

PMID- 17522740
TI  - [Premature death and disability profile in the population affiliated to the
      Mexican Institute of Social Security (IMSS)].
AB  - OBJECTIVE: To carry out estimations of the burden of disease for 129 causes in
      order to identify health priorities in the different geographic regions of the
      country and to present comparative data between 1995 and 2000. MATERIAL AND
      METHODS: Indicators such as disability-adjusted life years (DALYs) and disability
      adjusted life expectancy (DALE) were analyzed for the population covered by IMSS
      in 1995 and 2000; for both years, the methodology proposed by the Burden of
      Disease Worldwide Study was applied. Data corresponding to 1995 were analyzed in
      1997, while data corresponding to 2000 were analyzed in 2001. The comparative
      study was carried out in 2006 by IMSS, Mexico. RESULTS: The higher proportion of
      DALYs was due to chronic diseases, although the 2000 rate is 1.5 times higher
      than that of 1995. Priorities that were identified were diabetes mellitus,
      ischemic cardiopathy, and cerebrovascular disease, with a loss that is mainly
      accounted for by premature death, as well as by diseases related to disability
      with an important burden of disease, such as AIDS or depression. Epidemiological
      backlogs can still be observed. CONCLUSION: The population covered by IMSS is
      still in a phase of epidemiologic transition, favoring polarization in health
      conditions. Health policies need to be directed toward bringing about an improved
      response and reversing the trend in diseases that represent an institutional risk
      for the financing of health care.

PMID- 17522739
TI  - Assessing phytochemical intake in a group of Mexican women.
AB  - OBJECTIVE: Identify the content of selected phytochemicals (PHYs) in Mexican
      foods and evaluate the reliability of a food frequency questionnaire (FFQ) in
      assessing PHYs intake among Mexican women. MATERIAL AND METHODS: Values for PHYs
      content were obtained from four different data sets. PHYs intake was assessed in
      50 women of reproductive age enrolled in a longitudinal cohort study. Values were
      obtained from a FFQ administered twice, one year apart in order to evaluate its
      reliability. Selected PHYs included flavonol (FOL), flavones (FES), flavanol
      (FAL), secoisolariciresinol (SE), matairesinol (MA), lariciresinol (LA),
      pinoresinol (PI), cynamic acid (CA) and coumestrol (CU). RESULTS: Daily PHYs
      intake ranged from 1.3 microg +/- 0.9 for MA to 116.3 +/- 43.8 mg for CA. The
      adjusted correlation coefficients ranged from 0.17 for FAL to 0.47 for LA. Pinto
      beans, oranges, hot sauce, broccoli, apples and onions were the main sources of
      the selected PHYs daily intake. DISCUSSION: The results of this study contribute
      to our understanding of the consumption of PHYs in the Mexican diet, and would
      help evaluate their potential health impact.

PMID- 17522741
TI  - [The right to have health protection].
AB  - This article intends to analyze how the health good or the right to have health
      protection should be distributed, following the definition established by the
      Mexican Constitution. This legal definition will be contrasted with the way in
      which the expenditure on health is actually distributed and financed, and the
      implications of this. The distribution of this expenditure, in turn, will be
      compared to another social good of great relevance: education, which consumes an
      even larger proportion of the national fiscal resources. Finally, the article
      will suggest a possible explanation for this fact and provide some ideas
      regarding its implications.

PMID- 17522742
TI  - [Globalization and new public health].

PMID- 17522744
TI  - Diffusion-weighted imaging in transient global amnesia exposes the CA1 region of
      the hippocampus.
AB  - INTRODUCTION: Transient global amnesia (TGA) is characterized by a sudden onset
      of anterograde amnesia without alteration of consciousness or personal identity.
      Interestingly, recent studies have reported a high frequency of small high-signal
      abnormalities in the hippocampus with diffusion-weighted (DW) imaging, and
      ischemia has been proposed as an etiology of TGA. We hypothesized that TGA
      lesions occur preferentially in the CA1 region of the hippocampus, known to be
      susceptible to ischemia. METHODS: Over a 30-month period 34 patients with TGA
      underwent MRI including DW imaging within 4 days of symptom onset. Patients with
      high-signal abnormalities in the hippocampus on the initial DW images underwent
      subsequent DW and T2-weighted imaging in the coronal plane to identify the
      precise lesion locations. RESULTS: Fourteen patients had small (1-3 mm) high
      signal abnormalities in the hippocampus unilaterally on DW images. One of these
      patients had two lesions in one hippocampus and therefore in total 15 lesions
      were identified: four in the hippocampal head, and 11 in the body. Eleven lesions
      in ten patients with available coronal images were clearly demonstrated on both
      coronal DW and T2-weighted images and were localized to the lateral portion of
      the hippocampus, corresponding to the CA1 region. CONCLUSION: Lesions associated
      with TGA were localized exclusively to the lateral portion of the hippocampus
      corresponding to the CA1 region. This finding supports the ischemic etiology of
      TGA; however, the pathophysiological mechanism involved requires further study.

PMID- 17522746
TI  - Risk behaviours, victimisation and mental distress among adolescents in different
      family structures.
AB  - BACKGROUND: Previous studies have shown an elevated risk with regard to social
      and behavioural domains in adolescents of single parents. However, the diversity
      of single parent families concerning gender of the resident parent has seldom
      been taken into account when investigating the relation between family structure
      and children's negative outcomes. Thus, the aim of this study was to investigate
      risk behaviours, victimisation and mental distress among adolescents in different
      family structures using more detailed sub-groups of single parents (i.e., single
      mother, single father and shared physical custody). METHODS: The sample consisted
      of 15,428 ninth graders from all municipal and private schools in the county of
      Stockholm (response rate 83.4%). Risk behaviours included use of alcohol, illicit
      drugs and smoking. Victimisation was measured by experiences of exposure to
      bullying and physical violence. Mental distress was assessed with the
      anxious/depressed and aggressive behaviour syndrome scales in the Youth Self
      Report (YSR). Bivariate and multivariate logistic regression analyses were used
      to investigate the associations between family structure and outcome variables.
      RESULTS: Adolescents in single-mother/father families were at higher risk of risk
      behaviours, victimisation and mental distress than their counterparts in two
      parent families. However, after control for possible confounders the associations
      between victimisation, aggressive behaviour problems and single motherhood were
      no longer significant, whereas these relations remained for children living with
      single fathers. Adolescents in shared physical custody run no increased risk of
      any of the studied outcomes (except drunkenness) after adjustment for covariates.
      Post hoc analyses revealed that adolescents in single-father families were at
      higher risk for use of alcohol, illicit drugs, drunkenness, and aggressive
      behaviour as compared to their peers in single-mother families, whereas no
      differences were found between adolescents in single-mother families and those in
      shared physical custody. CONCLUSIONS: Children of single parents should not be
      treated as a homogenous group when planning prevention and intervention
      programmes. Researchers and professionals should be aware of and consider the
      specific problems of single parent children and that their problems may vary
      depending on their living arrangements.

PMID- 17522748
TI  - Perceived social justice, long-term unemployment and health. A survey among
      marginalised groups in Austria.
AB  - OBJECTIVE: Although socially disadvantaged groups are known to have a high risk
      of poor health the involved mechanisms and psychosocial dynamics are not fully
      understood. Long-term unemployment and the perception of social justice may both
      additionally endanger health. We therefore set out to explore the specific impact
      of these two context variables on self-reported health, health behaviour, and
      resources in marginalised groups. METHODS: A structured interview survey was
      conducted in three federal provinces in Austria, which targeted a quota sample of
      486 subjects in long-term unemployment. RESULTS: Both, duration of long-term
      unemployment and low perceived social justice, are strongly associated with self
      reported poor health and low personal (internal) and social (external) health
      resources. The best differentiation of dependent variables concerning the
      univariate analyses was found with respect to social health resources, as all
      variables on this level significantly correlated with perceived social justice
      but not with duration of long-term unemployment. CONCLUSION: While this study
      does not allow to establish causal relationships, the associations we found
      suggest that also perceived social justice needs to be taken into account in
      interventions that are intended to foster equity in health among socially
      disadvantaged groups.

PMID- 17522749
TI  - Dissipation of pendimethalin in the garlic (Allium sativum L.) under subtropical
      condition.

PMID- 17522747
TI  - A cross-cultural study of employers' concerns about hiring people with psychotic
      disorder: implications for recovery.
AB  - INTRODUCTION: Employment discrimination is considered as a major impediment to
      community integration for people with serious mental illness, yet little is known
      about how the problem manifests differently across western and non-western
      societies. We developed a lay model based on Chinese beliefs and values in terms
      of Confucianism, Taoism, Buddhism, and folk religions which may be used to
      explain cross-cultural variation in mental illness stigma, particularly in the
      arena of employment discrimination. In this study, we tested this lay approach by
      comparing employers' concerns about hiring people with psychotic disorder for
      entry-level jobs in US and China. METHOD: One hundred employers (40 from Chicago,
      30 from Hong Kong, and 30 from Beijing) were randomly recruited from small size
      firms and interviewed by certified interviewers using a semi-structured interview
      guide designed for this study. Content analysis was used to derive themes, which
      in turn were compared across the three sites using chi-square tests. RESULTS:
      Analyses reveal that employers express a range of concerns about hiring an
      employee with mental illness. Although some concerns were raised with equal
      frequency across sites, comparisons showed that, relative to US employers,
      Chinese employers were significantly more likely to perceive that people with
      mental illness would exhibit a weaker work ethic and less loyalty to the company.
      Comparison of themes also suggests that employers in China were more people
      oriented while employers in US were more task-oriented. CONCLUSION: Cultural
      differences existed among employers which supported the lay theory of mental
      illness.

PMID- 17522750
TI  - Occurrence and distribution of polycyclic aromatic hydrocarbons (PAHs) in Bolgoda
      and Beira Lakes, Sri Lanka.
AB  - The pollution of polycyclic aromatic hydrocarbons (PAHs) has been widely used to
      assess the potential impact of anthropogenic activities on aquatic environments
      because their occurrence in water is closely tied to urban activities. Many PAHs
      possess mutagenic and carcinogenic properties (Menzie et al. 1992). PAH
      distribution and toxic potentials have therefore been the focus of numerous
      studies in waterways including the Great Lakes (USEPA Report 1994), Yanisei Bay
      (Dahle et al., 2003), and the Fraser River basin (Yunker et al., 2002). Sri
      Lanka, a small island nation with a dense population of about 20 million people,
      faces a multitude of environmental stresses ranging from deforestation to traffic
      congestion and the deterioration of water quality. This study was undertaken to
      understand the occurrence, sources, and potential impacts of PAHs in the
      waterways of Sri Lanka. Two lakes, Beira and Bolgoda, were selected for the study
      due to their economic value and high level of pollution. Beira Lake, situated in
      downtown Colombo, the capital city of Sri Lanka, is highly polluted. Sources of
      pollution are multifarious. For instance, clusters of communities have sprung up
      along the edges of the lake in recent times and many shacks have been built.
      These communities are generally not connected to municipal sewer systems and
      substantial quantities of domestic sewage and untreated wastewaters are
      discharged directly into the lake. Small industries have also grown rapidly
      around the lakes, most of which are not believed to have adequate facilities to
      treat industrial wastewater, especially organic wastes. In addition, Sri Lanka
      has experienced an upsurge of motor vehicles, including millions of three
      wheelers and minivans that are powered by leaded gasoline and diesel fuels.
      Traffic congestion and severe air pollution due to vehicle emissions are now
      common daily occurrences and are considered a major potential source of PAHs in
      the lakes. Although Bolgoda Lake is situated some distance from Colombo, it is
      heavily polluted due to the growing number of towns with an attendant increase in
      small businesses and various industries along its shores. These new developments
      have undoubtedly impacted the lake through the discharge of PAHs and other
      anthropogenic chemicals present in industrial wastewater and from street runoffs.
      The lake, additionally, receives a large quantity of pollutants from the
      industrial zone in the north. The pollution caused by PAHs has led to various
      studies on the distribution and origin of PAHs in the environment (Yunker et al.,
      1996; Budzinski et al., 1997). Based on the proportions of different PAHs, most
      studies aim to distinguish PAHs of petrogenic sources from those of pyrolytic
      origins. The PAHs of petrogenic origin, prevalent in coals and fossil fuels, are
      formed from diagenesis of sedimentary organic material under low to moderate
      temperature and tend to consist of low-molecular-weight PAHs with two to three
      aromatic rings (Potter et al., 1998). The pyrolytic PAHs, on the other hand, are
      formed at much higher temperatures (greater than 500 degrees C for example) and
      consist mainly of four or more aromatic rings (Commins, 1969). Thus, an increase
      in the proportion of higher-molecular-weight PAHs is taken to be indicative of
      contaminations of mainly pyrolytic origin. The prevalence of high-molecular
      weight PAHs in the urban dusts (Wise et al., 1988) and in atmospheric particles
      (Sicre et al., 1987) illustrates the chemistry of their formation at high
      temperature. The purpose of this study was to determine the PAH concentrations
      and distribution with respect to sampling location, origin and sources in two
      polluted lakes.

PMID- 17522751
TI  - Monitoring heavy metal pollution in San Antonio Bay, Rio Negro, Argentina.

PMID- 17522752
TI  - Contents of some metals in honeys from different regions in Turkey.

PMID- 17522754
TI  - The left inferior phrenic artery arising from left hepatic artery or left gastric
      artery: radiological and anatomical correlation in clinical cases and cadaver
      dissection.
AB  - BACKGROUND: The purpose of this study is to assess angiographic and CT appearance
      of left inferior phrenic artery (LIPA) arising from left hepatic or left gastric
      artery and to recognize its specific anatomical location with the help of cadaver
      dissection. METHODS: We retrospectively reviewed 761 abdominal angiographies and
      found 13 patients (1.7%) with LIPA arising from left hepatic or left gastric
      artery. We classified those origins and assessed radiological features. We also
      presented a cadaver dissection to identify anatomical location of LIPA arising
      from left hepatic artery. RESULTS: The origin of the LIPA was classified as
      follows: (a) left hepatic artery: four, (b) accessory left gastric artery: one,
      (c) accessory left hepatic artery: three, and (d) left gastric artery: five
      patients. The proximal portion was located in gastrohepatic ligament and its
      distal portion was located in front of esophageal hiatus. In a cadaver
      dissection, the proximal portion ascends along ligamentum venosum and distal
      portion courses along superior aspect of left hemi diaphragm in front of
      esophagus. CONCLUSION: The LIPA rarely arises from left hepatic or left gastric
      artery. The proximal portion was located in gastrohepatic ligament and the distal
      portion runs in front of the esophageal hiatus.

PMID- 17522755
TI  - Deformation of the pelvic floor muscles during a vaginal delivery.
AB  - Pelvic floor dysfunction is a hidden problem with a magnitude unknown to many.
      Statistics show that one in every ten women will have pelvic floor dysfunction so
      severe that it will require surgery. Several studies have shown that pelvic floor
      injuries during a vaginal delivery can be considered a significant factor in the
      development of urinary incontinence, fecal incontinence, and pelvic organ
      prolapse. The objective of the present work is to contribute to the clarification
      of the mechanisms behind pelvic floor disorders related to a vaginal delivery.
      For this purpose, a numerical simulation based on the finite element method was
      carried out. The finite element model intends to represent the effects that the
      passage of a fetal head can induce on the muscles of the pelvic floor, from a
      mechanical point of view. The model used for the simulation represents the pelvic
      bones, with the attached pelvic floor muscles and the fetus. In this work, we
      simulated the movements of the fetus during birth, in vertex position. We
      simulated the engagement, descent, flexion, internal rotation, and extension of
      the fetal head. Results for the pelvic floor stretch values obtained during the
      passage of the fetus head are presented; the deformation field is also shown. The
      results were obtained using the finite element method and a three-dimensional
      computer model of the pelvic floor and fetus. The maximum deformation obtained
      was 0.66 for a vertical displacement of the fetal head of approximately 60 mm.

PMID- 17522756
TI  - Growth kinetics of polymer crystals in bulk.
AB  - Temperature-dependent measurements of spherulite growth rates carried out for i
      polystyrene, poly(epsilon -caprolactone) and linear polyethylene show that the
      controlling activation barrier diverges at a temperature which is 14K, 22K and
      12K, respectively, below the equilibrium melting points. We discuss the existence
      of such a "zero growth temperature" T(zg) in the framework of a recently
      introduced thermodynamic multiphase scheme and identify T(zg) with the
      temperature of a (hidden) transition between the melt and a mesomorphic phase
      which mediates the crystal growth. The rate-determining step in our model of
      crystal growth is the attachment of chain sequences from the melt onto the
      lateral face of a mesomorphic layer at the growth front. The necessary
      straightening of the sequence prior to an attachment is the cause of the
      activation barrier. A theory based on this view describes correctly the
      observations. With a knowledge of T(zg) it is possible to fully establish the
      nanophase diagram describing the stability ranges of crystalline and mesomorphic
      layers in a melt. An evaluation of data from small-angle X-ray scattering,
      calorimetry and optical growth rate measurements yields heats of transition and
      surface free energies of crystals and mesophase layers, as well as the activation
      barrier per monomer associated with the chain stretching. According to the
      theory, the temperature dependence of the crystallization rate is determined by
      both the activation energy per monomer and the surface free energy of the
      preceding mesomorphic layer. Data indicate that the easiness of crystallization
      in polyethylene is first of all due to a particularly low surface free energy of
      the mesomorphic layer.

PMID- 17522757
TI  - Thermomechanical effects in uniformly aligned dye-doped nematic liquid crystals.
AB  - We show theoretically that thermomechanical effects in dye-doped nematic liquid
      crystals when illuminated by laser beams, can become important and lead to
      molecular reorientation at intensities substantially lower than that needed for
      optical Freedericksz transition. We propose a 1D model that assumes homogenous
      intensity distribution in the plane of the layer and is capable to describe such
      a thermally induced threshold lowering. We consider a particular geometry, with a
      linearly polarized light incident perpendicularly on a layer of homeotropically
      aligned dye-doped nematics.

PMID- 17522758
TI  - Diet and activity budget of Rhinopithecus roxellana in the Qinling Mountains,
      China.
AB  - We collected data on diet and daytime activity budget, and investigated the
      phenology of food trees and food abundance for a group of Rhinopithecus roxellana
      on the East Ridge of Yuhuangmiao in the Qinling Mountains from November 2001 to
      December 2003. We calculated the seasonal activity budget using data collected by
      scan sampling from 84 full-day observations (winter 16, spring 18, summer 28,
      autumn 22 days). During scan sampling we recorded behavioral states, and the food
      items and species consumed. The subjects consumed 84 plant species, including
      trees and shrubs of 29 families, and lichens. Food species varied seasonally. The
      overall diet of R. roxellana consisted of 29.4% fruit/seeds, 29.0% lichens, 24.0%
      leaves, 11.1% bark, 4.2% buds, 1.3% twigs and 1.0% unidentified items. Because
      the abundance of different food items varied seasonally, the monkeys had to shift
      their major food items seasonally. The annual activity budget of R. roxellana was
      36.2% time spent resting, 35.8% feeding, 22.9% moving, and 5.1% other behavior.
      Seasonal changes in activity budget were observed. R. roxellana spent more time
      moving in autumn, when the quality of the food might be highest, and least time
      moving in winter when the food quality might be lowest. Thus, this type of monkey
      has a passive foraging strategy.

PMID- 17522759
TI  - Surgery for ruptured abdominal aortic aneurysm with an aortocaval and iliac vein
      fistula.
AB  - The purpose of this study was evaluate the operative procedure and outcome of
      abdominal aortic aneurysm (AAA) patients with aortocaval fistula (ACF) and iliac
      vein fistula. From 1982 through 2004, we experienced five AAA patients associated
      with spontaneous aortocaval and aortoiliac venous fistula who underwent repair of
      AAA. Three patients were in hypovolemic shock, including one patient with
      cardiopulmonary arrest on admission who required cardiopulmonary resuscitation
      before surgery. These three ACF patients with hypovolemic shock underwent
      emergency operation and two patients with stable hemodynamic state underwent
      urgent operation. One of two ACF patients with stable condition was associated
      with unstable angina. One AAA patient with ACF-complicated angina underwent AAA
      repair with coronary artery bypass grafting; the remaining four patients
      underwent 3 bifurcated graft and 1 tube graft implantation. All surgical
      treatment of the fistula included direct closure within the aorta under digital
      compression in four patients and inferior vena cava clamp in one. The mortality
      rate was 25%. One ACF patient with retroperitoneal hematoma died of bleeding.
      Survival for ACF depends on early diagnosis and prompt surgical repair.
      Aortocaval fistula complicated with a rupture of aneurysm into retroperitoneal
      space had a severe fatal prognosis compared with uncomplicated ACF.

PMID- 17522760
TI  - Cor triatriatum sinistrum: surgical experience in Taiwan.
AB  - PURPOSE: Cor triatriatum sinister, more commonly referred to as cor triatriatum
      (CT), is characterized by a common pulmonary venous chamber (proximal chamber)
      separated from the left atrium (distal chamber) by a fibromuscular septum. This
      report of our experience updates the surgical results of this anomaly in the
      Asian population. METHODS: Between January 1992 and May 2005, nine patients with
      cor triatriatum underwent surgical correction at Chang Gung Memorial Hospital. We
      retrospectively analyzed their cardiac anatomy, clinical data, surgical
      procedures and follow-up data. RESULTS: The mean age at surgery was 260+/-215
      days (range, 20-790 days), with the exception of one patient who underwent
      surgery at 31 years of age. Three patients had a partial anomalous pulmonary
      venous connection, one had a complete atrioventricular canal defect, and one had
      another major complex cardiac anomaly. Eight corrective operations and one
      palliative operation were performed. There was no surgical mortality. The mean
      follow-up time was 52.1+/-43.6 months (range, 17-139 months). CONCLUSION: Our
      findings show that surgical correction is efficient and safe for this rare
      cardiac anomaly.

PMID- 17522761
TI  - Gastrointestinal stromal tumor of the rectum: an analysis of seven cases.
AB  - PURPOSE: Gastrointestinal stromal tumors (GISTs) rarely originate in the rectum.
      We investigated the clinicopathologic characteristics of rectal GISTs. METHODS:
      We analyzed the medical records of seven patients who underwent surgery for GIST
      of the rectum between 1998 and 2003. RESULTS: There were two men and five women
      with a median age of 55 years (range, 41-72 years) at the time of diagnosis. The
      median follow-up period was 23 months (range, 7-75 months). The chief symptoms
      were hematochezia, constipation, and anal pain. All patients underwent curative
      resection; in the form of abdominoperineal resection in five patients, transanal
      excision in one, and Hartmann's operation with prostatectomy in one. The median
      tumor size was 6.6 cm (range, 1-12 cm). Four patients received adjuvant radiation
      therapy. Local recurrence developed in two patients; 54 months and 23 months
      after surgery, respectively. CONCLUSION: The common symptoms of rectal GIST were
      the same as those of other rectal tumors. Curative surgical resection should be
      done, but further studies are necessary to investigate better adjuvant treatment
      strategies for patients with rectal GISTs.

PMID- 17522762
TI  - Possible protection of sinusoidal endothelial cells by endothelin B receptor
      during hepatic warm ischemia-reperfusion.
AB  - PURPOSE: Endothelins (ETs) are important regulators of the hepatic
      microcirculation. We investigated the pure biological roles of endothelin B
      receptors (ETB-Rs) on hepatic warm ischemia-reperfusion (I/R) injury using ETB-R
      deficient spotting lethal (sl) rats. METHODS: Homozygous (sl/sl) and wild-type
      (+/+) rats were exposed to 60 min of 92% partial hepatic ischemia and then were
      killed at 2, 6, and 24 h, and 3 and 7 days after reperfusion. We measured the
      serum alanine aminotransferase (ALT) levels to assess hepatocyte injury, and the
      serum hyaluronic acid (HA) levels and factor VIII-related antigen (FVIIIRAg)
      staining to assess sinusoidal endothelial cell (SEC) injury. We also measured the
      concentrations of ET-1 and nitrite (NO2-) and nitrate (NO3-) of liver tissue
      samples. RESULTS: Although no significant difference was observed in the ALT
      levels, the HA levels were significantly elevated at an early stage after
      reperfusion in the sl/sl rats. Regarding FVIIIRAg staining, positive SECs were
      enhanced in the sl/sl rats. The ET-1 levels were also significantly elevated at
      an early stage after reperfusion in the sl/sl rats. Regarding the NO2- and NO3-
      levels, no significant difference was observed. CONCLUSION: Endothelin B receptor
      was shown to have a protective effect on SECs through the inhibition of ET-1
      during hepatic warm I/R injury.

PMID- 17522763
TI  - Effects of calcium channel blocker azelnidipine on experimental abdominal aortic
      aneurysms.
AB  - PURPOSE: Azelnidipine has recently been recognized in vascular remodeling.
      However, the effects of azelnidipine on aneurysmal disease have not yet been
      studied. The aim of this study was to evaluate whether azelnidipine can inhibit a
      further expansion of aneurysmal disease. METHODS: Experimental abdominal aortic
      aneurysms (AAAs) were created in a rat model by perfusing elastase. The rats in
      the first group received no treatment (n=10). In the second group (n=10)
      azelnidipine (2 mg/kg) was administered to the animals from 3 days before
      perfusion. The aortic diameter (AD) was measured at the time of initial surgery
      and death on postoperative day 14. The production of matrix metalloproteinases
      (MMP)-2 and -9 was analyzed by gelatin zymography. RESULTS: The aortic diameter
      was smaller in the azelnidipine group than in the control (7.875+/-1.454 vs
      10.745+/-0.551 mm, P<0.01). the active MMP-2 and MMP-9 levels decreased in the
      azelnidipine group. Hematoxylin-eosin and elastin staining revealed fewer changes
      in the inflammatory infiltrate and degradation of elastin in the azelnidipine
      group. CONCLUSION: Azelnidipine reduced the expansion of experimental AAAs.
      Azelnidipine therefore appears to influence the inflammatory oxidative response
      seen in AAAs while also decreasing the MMP-2 and MMP-9 levels. In addition,
      azelnidipine inhibited aortic dilatation.

PMID- 17522764
TI  - Interferon-beta inhibits liver metastases from murine colon 26 carcinoma and its
      highly metastatic variant.
AB  - PURPOSE: The antitumor effects of Interferon-beta (IFN-beta) are due to its
      direct inhibition of cell proliferation, immunostimulatory activity, and the
      inhibition of angiogenesis. We investigated the mechanism of the effects of IFN
      beta on a murine colon 26 cell line (CT 26) and its highly metastatic variant
      (L5). METHODS: We examined its inhibitory effects on cell proliferation in vitro
      and the development of liver metastases in vivo. RESULTS: The proliferation of CT
      26 in vitro was inhibited by IFN-beta in a dose- and time-dependent manner. The
      number of metastases was reduced in mice inoculated with CT 26 (P<0.01) and L5
      (P<0.01) on Day 14 after treatment with IFN-beta. The median survival rate of the
      mice inoculated with L5 administered IFN-beta every other day, or every day was
      higher than in the control group (P<0.05). A dorsal air sac assay demonstrated
      that IFN-beta inhibited angiogenesis in mice inoculated with CT 26, but the
      effects disappeared with aminoguanidine, an inducible nitric oxide synthase
      inhibitor. CONCLUSION: These results showed that IFN-beta directly inhibits the
      proliferation of CT 26. In addition, the in vivo experiments suggested that IFN
      beta might effectively inhibit liver metastases.

PMID- 17522765
TI  - A comparison of the effects of diltiazem and glyceryl trinitrate ointment in the
      treatment of chronic anal fissure: a randomized clinical trial.
AB  - PURPOSE: Anal fissure is a common problem affecting all age groups with an equal
      incidence in both sexes. Traditional surgical treatments, like manual anal
      dilatation or a sphincterotomy, effectively heal most fissures within a few weeks
      but such procedures may result in anal incontinence. In recent years, various
      medical therapies have been used for the treatment of chronic anal fissure
      without fear of incontinence. METHODS: Ninety patients with a symptomatic anal
      fissure were randomly divided into three groups. Group I was treated with 2%
      diltiazem ointment, Group II was treated with 0.2% glyceryl trinitrate (GTN)
      ointment, and Group III was kept as the control group. The improvement in the
      signs and symptoms, the time taken for healing, and side effects were recorded in
      each group. The patients were followed up monthly and then every 3 months for any
      recurrence of fissure. Comparative evaluations of the three groups regarding an
      improvement in symptoms, progress in healing, appearance of side effects, and
      recurrence were made using the Tukey HSD test. RESULTS: Diltiazem ointment was
      found to be superior regarding pain relief, fewer side effects, and late
      recurrence as compared with GTN ointment. CONCLUSION: Diltiazem ointment (2%) and
      GTN ointment (0.2%) are both effective treatment modalities for chronic anal
      fissure, with diltiazem giving better patient outcome.

PMID- 17522766
TI  - Ectopic thyroid gland on the ascending aorta with a partial pericardial defect:
      report of a case.
AB  - Intrathoracic ectopic goiters are rare. To our knowledge, only two reports of
      thyroid tissue on the aorta have been reported in the English literature. A 42
      year-old woman was found to have a right paracardiac mass. Sternotomy revealed a
      firm and encapsulated tumor attached to the anterolateral surface of the
      ascending aorta and a defect in the right superior part of the pericardium. The
      mass was completely excised and histopathologic examination confirmed a
      multinodular goiter. We discuss the features of this rare tumor.

PMID- 17522767
TI  - Large organized thrombus of the tricuspid valve: report of a case.
AB  - We report the case of a 49-year-old woman with a large organized tricuspid valve
      thrombus in a structurally normal heart. Preoperative echocardiogram showed a
      large irregular-shaped mass, approximately 5 cm in diameter, moving from the
      right atrium into the right ventricle. The assumed preoperative diagnosis was
      cardiac metastasis of uterine sarcoma because she had undergone surgery for
      uterine sarcoma 15 years earlier. However, histologic examination revealed an
      organized thrombus without tumor components.

PMID- 17522768
TI  - Pleomorphic adenoma of the trachea mimicking bronchial asthma: report of a case.
AB  - Benign tracheal tumors are rare and difficult to diagnose. A delay in diagnosis
      is common because the symptoms mimic those of bronchial asthma. We report the
      case of a 42-year-old woman who was treated for asthma for 2 years before a
      diagnosis of pleomorphic adenoma of the trachea was made. To our knowledge, only
      33 patients with pleomorphic adenoma of the trachea have been reported. We
      treated our patient by performing circumferential segmental tracheal resection
      and end-to-end anastomosis. A dynamic Y-stent was implanted for tracheal stenosis
      soon after the operation and it was removed 2 years later. The patient is now
      asymptomatic and no recurrence has been detected in the 5 years since diagnosis.

PMID- 17522769
TI  - Pulmonary intimal sarcoma treated by a left pneumonectomy with pulmonary
      arterioplasty under cardiopulmonary bypass: report of a case.
AB  - Intimal sarcoma of the pulmonary artery is a rare disease. This neoplasm was
      characterized by an aggressive extension to the lumen of the pulmonary artery,
      thus mimicking a pulmonary thromboembolism. We herein report a 44-year-old woman
      who was diagnosed as having primary intimal sarcoma of the left lung
      preoperatively by transbronchial biopsy. The tumor originated in the pulmonary
      artery in the left lung, extending to the main pulmonary trunk via the pulmonary
      arterial lumen, thus resulting in stenosis of the main pulmonary trunk. A
      complete resection of the tumor with the left pneumonectomy and the pulmonary
      arterioplasty was successfully performed under cardiopulmonary bypass with vacuum
      assisted venous drainage.

PMID- 17522770
TI  - Esophageal schwannoma: report of a case.
AB  - We report a case of esophageal schwannoma in a 46-year-old woman who presented
      with rapidly progressive dyspnea and dysphagia. Chest computed tomography showed
      a large mediastinal mass, which was extrinsically compressing the trachea, widely
      adjacent to the upper thoracic esophagus. We performed an axillary right
      thoracotomy to enucleate the tumor, which was located in the esophageal muscle
      layer. A definite diagnosis of esophageal schwannoma was made from the pathologic
      findings, which included positive immunohistochemical staining for S-100 protein
      and negative staining for c-kit and CD34.

PMID- 17522771
TI  - Gastric antral vascular ectasia--an unusual cause of gastric outlet obstruction:
      report of a case.
AB  - Gastric antral vascular ectasia is an important cause of gastric bleeding. We
      herein report a case of gastric outlet syndrome due to a gastric antral vascular
      ectasia in a patient with a negative history for anemia or gastric bleeding. The
      patient underwent an antral resection. The specimen showed vascular ectasia,
      fibromuscular hyperplasia, and fibrin thrombosis, especially localized in the
      submucosa. The pathogenesis of this syndrome remains unclear. Surgery in cases of
      gastric outlet obstruction is the only reliable method to cure the patient. An
      antrectomy has been shown to be the procedure of choice. It carries a remarkably
      low rate of long-term sequelae and it can be performed in the majority of cases
      with low risk, especially in those patients not affected by cirrhosis or portal
      hypertension.

PMID- 17522772
TI  - Ileal malignant melanoma causing intussusception: report of a case.
AB  - Cutaneous malignant melanoma (MM) often metastasizes to the gastrointestinal (GI)
      tract; however, primary MM of the small intestine is a controversial diagnosis.
      We report the case of a 76-year-old woman found to have a primary MM in the
      ileum. After clinical evaluation, the radiological workup, which included
      magnetic resonance enteroclysis (MRE), revealed a large polypoid intraluminal
      tumor. She underwent laparotomy and the lesion was excised. Histological
      examination of the resected specimen revealed morphological and
      immunohistochemical characteristics of MM and a detailed postoperative
      examination failed to identify a primary lesion on the skin, anus, oculus, or any
      other site. The patient died of brain metastasis 6 months after surgery.
      According to our review of the literature, this is the first case of primary MM
      of the small intestine diagnosed with the help of MRE.

PMID- 17522773
TI  - Laparoscopic appendectomy for appendiceal endometriosis presenting as acute
      appendicitis: report of a case.
AB  - Endometriosis is a relatively common disorder in women of reproductive age;
      however, appendiceal endometriosis is rare. Thus, a definitive diagnosis is
      likely to be established only by histology of the appendix. We report a case of
      endometriosis of the appendix in a 42-year-old woman who presented with symptoms
      of acute appendicitis. We treated the patient by performing laparoscopic
      appendectomy, which resulted in a good outcome.

PMID- 17522774
TI  - Volvulus of an appendiceal mucocele: report of a case.
AB  - Few cases of volvulus of an appendiceal mucocele have been reported. The
      mechanism of torsion seems to be similar to that suggested for ovarian or
      appendegeal torsion, where a solid organ or mass fixed onto a narrow stalk is a
      precondition. We report the case of a young woman who presented with signs and
      symptoms of acute appendicitis. Computed tomography showed a cystic mass of fluid
      consistency in the right lower quadrant. An emergency laparoscopy revealed a 720
      degrees torsion of a gangrenous mucocele around the proximal part of the
      appendix. We performed a laparoscopic appendectomy and she recovered
      uneventfully. The presentation of volvulus of an appendiceal mucocele can mimic
      other common conditions. Prompt surgical intervention is essential to prevent
      gangrene and perforation. The combination of a cystic, right lower quadrant mass,
      and clinical findings suggestive of acute appendicitis should alert the clinician
      to include volvulus of an appendiceal mucocele in the differential diagnosis.

PMID- 17522775
TI  - Hemothorax as the clinical presentation of a pancreaticopleural fistula: report
      of a case.
AB  - Pancreaticopleural fistula is a rare complication of acute pancreatitis with
      pancreatic pseudocyst. We report the case of a 39-year-old man admitted for
      respiratory distress. Chest X-ray showed a pleural effusion, and thoracentesis
      yielded bloody fluid. Computed tomography (CT) scan showed a multiloculated
      pleural effusion and sagittal reconstruction revealed a fistulous tract between
      the pleura and a pancreatic pseudocyst. We treated the acute hemothorax
      complicating the pancreaticopleural fistula by performing urgent thoracotomy with
      the evacuation of blood and clots and lung decortication. We also gave the
      patient somatostatin and performed endoscopic retrograde cholangiopancreatography
      with sphincterotomy, and placed a pancreatic stent. The patient recovered well.

PMID- 17522776
TI  - Congenital solitary intrahepatic biliary cyst in a newborn: report of a case.
AB  - A solitary liver cyst (SLC) is a nonparasitic cyst of congenital origin. Its
      cause is unknown, but it may develop in the form of a simple cyst or a biliary
      cyst. Solitary liver cysts are extremely rare and usually symptomatic in infancy
      whereas they are most often detected incidentally in adulthood. Despite advanced
      imaging techniques, the differential diagnosis of SLC may still be difficult.
      Surgical intervention is required for histopathological verification, to relieve
      symptoms and prevent complications such as infection, cyst rupture, and
      hemorrhage. Although total excision of SLC is desirable to impede recurrences,
      partial excision may be adequate when total excision is impossible. We report the
      case of a newborn with a progressively enlarging solitary intrahepatic biliary
      cyst. We discuss the etiology, differential diagnosis, and treatment options for
      this rare entity.

PMID- 17522777
TI  - Spontaneous regression of inflammatory pseudotumor of the liver: report of three
      cases.
AB  - Inflammatory pseudotumor (IPT) of the liver is a rare benign hepatic lesion that
      sometimes mimics malignant tumors. An accurate diagnosis of IPT is important to
      avoid unnecessary surgery. We herein report three cases of IPT of the liver that
      spontaneously regressed and were successfully diagnosed without a surgical
      resection. Malignant tumors were initially suspected based on the initial imaging
      findings, including ultrasonography, computed tomography (CT), and magnetic
      resonance imaging. In particular, a delayed enhancement in the periphery of the
      masses was observed on dynamic CT scans, similar to the imaging results for
      metastatic tumors or intrahepatic cholangiocarcinomas. The serum levels of C
      reactive protein were elevated in all three patients (6.6, 3.4, and 1.5 mg/dl),
      while the serum levels of tumor markers were almost within the normal ranges
      (carcinoembryonic antigen, <5 ng/ml; carbohydrate antigen 19-9, 201, 3, and 14
      U/ml). Serial repeated imaging studies over the course of a month showed the
      spontaneous regression of the hepatic tumors, thus enabling us to make a
      diagnosis of IPT without a surgical resection. A percutaneous biopsy confirmed
      the histology in one case. The regression of tumors on repeated images should
      play a key role in making an accurate diagnosis of IPT.

PMID- 17522778
TI  - Multiple inflammatory pseudotumor of the liver, mimicking cholangiocarcinoma with
      tumor embolus in the hepatic vein: report of a case.
AB  - A 68-year-old Japanese woman complaining of general fatigue and intermittent high
      fever was admitted to our hospital. Abdominal ultrasonography showed two tumors
      in the lateral segment of the liver, with soft tissue in the left hepatic vein
      that was considered to be a tumor embolus. A diagnosis of cholangiocarcinoma was
      made based on various radiological and laboratory examinations and therefore a
      surgical resection was performed. Microscopically, the tumor consisted of
      inflammatory cells, which had aggressively invaded the hepatic vein and Arantius'
      duct. The pathological diagnosis was inflammatory pseudotumor (IPT) that had
      invaded the hepatic vein. Although many cases of hepatic IPT have been previously
      reported, cases of hepatic IPT massively invading the hepatic vein are very rare
      as far as we could determine, based on a literature search. We herein report this
      case and discuss the diagnosis and treatment regarding hepatic IPT with massive
      venous invasion.

PMID- 17522779
TI  - The mouse pattern electroretinogram.
AB  - Mouse models of optic nerve disease such as glaucoma, optic neuritis, ischemic
      optic neuropathy, and mitochondrial optic neuropathy are being developed at
      increasing rate to investigate specific pathophysiological mechanisms and the
      effect of neuroprotective treatments. The use of these models may be greatly
      enhanced by the availability of non-invasive methods able to monitor retinal
      ganglion cell (RGC) function longitudinally such as the Pattern Electroretinogram
      (PERG). While the use of the PERG as a tool to probe inner retina function in
      mammals is known since 25 years, relatively less information is available for the
      mouse. Here, the PERG technique and the main applications in the mouse are
      reviewed.

PMID- 17522780
TI  - Kinetics of aqueous flare, intraocular pressure and virus-DNA copies in a patient
      with cytomegalovirus iridocyclitis without retinitis.
AB  - BACKGROUND: A case report of recurrent unilateral granulomatous iridocyclitis
      with ocular hypertension without retinitis caused by cytomegalovirus (CMV) in an
      immunocompetent patient. METHODS: Aqueous humor was analysed by multiplex PCR to
      detect viral DNA, and real-time PCR was used to evaluate virus copies before and
      after anti-virus treatments. Inflammation of the anterior chamber was evaluated
      by a laser flare photometry. RESULTS: Genomic DNA of CMV - but not of other
      herpes viruses - was detected in the aqueous humor. Quantitative real-time PCR
      revealed 2.3 x 10(5) copies/ml of CMV DNA from the specimen. Oral valganciclovir
      was added to the ongoing treatment, which consisted of topical corticosteroid,
      timolol and latanoprost as well as systemic acetazolamide, resulting in the
      reduction of aqueous flare correlated with the reduction of virus copies in
      aqueous humor. CONCLUSIONS: In this case of CMV-related iridocyclitis in an
      immunocompetent patient, specific additional anti-viral therapy was effective in
      controlling inflammation of anterior chamber but, as is so often the case, it was
      unable to control intraocular pressure. We show that inflammatory activity
      correlated well with the number of virus copies in the aqueous humor.

PMID- 17522782
TI  - Central retinal artery occlusion in an ANCA negative Churg-Strauss syndrome
      patient.
AB  - PURPOSE: To describe a central retinal artery occlusion in a patient with
      antineutrophil cytoplasmic antibody (ANCA) negative Churg-Strauss syndrome.
      METHODS: Review of clinical and laboratory findings of a 44-year-old woman with
      ANCA negative Churg-Strauss syndrome that developed sudden vision loss in left
      eye. RESULTS: Left central retinal artery occlusion was diagnosed by retinal
      whitening, a cherry-red spot, and delayed arterial filling on fluorescein
      angiography. Perinuclear ANCA and cytoplasmic ANCA were negative. CONCLUSION:
      Central retinal artery occlusion can occur in ANCA negative Churg-Strauss
      syndrome. Patients with this diagnosis should be considered for prophylactic high
      dose corticosteroid, regardless of their ANCA status.

PMID- 17522781
TI  - Bilateral orbital myeloid sarcoma as initial manifestation of acute myeloid
      leukemia.
AB  - BACKGROUND: Granulocytic sarcoma is a rare orbital complication of acute
      leukemia. It concerns primarily children under 10 years of age suffering from
      primitive acute myeloid leukemia. The diagnosis is made by clinical examination,
      computed tomography and confirmed by haematological investigations. The treatment
      approach is based on chemotherapy associated with intravenous steroid therapy.
      CASE REPORT: We report the case of a 6-year-old girl who presented with bilateral
      proptosis revealing acute myeloid leukemia. The patient was treated by a
      combination of chemotherapeutic drugs in two phases, associated with intravenous
      steroids. After a follow-up period of 24 months, the patient was in complete
      remission. CONCLUSION: The diagnosis of granulocytic sarcoma should be considered
      in any orbital mass of uncertain origin, particularly if it is bilateral. Special
      stains and immunohistochemistry play an important role in the diagnosis.

PMID- 17522783
TI  - Slit-lamp-adapted optical coherence tomography of pupillary block after Artisan
      lens implantation for aphakia.
AB  - We present a report on a patient with acute glaucoma. Slit-lamp-adapted optical
      coherence tomography (SL-OCT) confirmed a pupillary block due to a claw lens.
      After laser iridectomy the situation stabilized. Thus, SL-OCT allows non
      invasive, high-resolution imaging in acute angle-closure glaucoma and may be
      helpful with the differential diagnosis of pupillary block glaucoma and the
      documentation of the surgical result.

PMID- 17522784
TI  - Bilateral thalamic astrocytoma.
AB  - We present a 68-year-old woman who presented with symptoms of frontotemporal
      dementia. Brain MRI revealed tumor mass in both thalami and according to WHO
      classification, the tumor corresponded to diffuse fibrillary astrocytoma grade
      II. This case points to the role of neuroimaging in patients presenting with
      classical symptoms of dementia.

PMID- 17522785
TI  - FOXG1 dysregulation is a frequent event in medulloblastoma.
AB  - Medulloblastomas represent 20% of malignant brain tumors of childhood. Although,
      they show multiple, non-random genomic alterations, no common, early genetic
      event involving all histologic types of medulloblastomas have been described.
      Nineteen medulloblastomas were analyzed using chromosomal comparative genomic
      hybridization (cCGH). Nine tumors with the most frequent number of genetic
      changes were further analyzed using bacterial artificial chromosome array CGH
      (aCGH). With aCGH, the frequency of gains and losses were higher than with cCGH.
      Chromosome 2p gains spanning 2p11-2p25 including N-myc locus, 2p24.1 were
      detected in 5/9 (55%) tumors while 14q12 gains were detected in 6/9 (67%) tumors.
      The 14q12 locus overlapped with the FOXGI gene locus. Quantitative real time PCR
      showed a 2-7-fold copy gain for FOXG1 in all the nine tumors. Protein expression
      was demonstrated by immunohistochemistry in all histologic types. The expression
      of FOXG1 and p21cip1 showed an inverse relationship. FOXG1 copy gain (>2 to 21
      folds) was seen in 93% (55/59) of a validating set of tumors and showed a
      positive correlation with protein expression (Spearman's rank order correlation
      coefficient = 0.276; P = 0.038) representing the first report of FOXG1
      dysregulation in medulloblastoma. Modulation of FOXG1 expression in DAOY cell
      line using siRNA showed a modest decrease in proliferation with a 2-fold
      upregulation of p21cip1. Current reports indicate that FOXG1 represses TGF-beta
      induced expression of p21cip1 and cytostasis, and forms a transcriptional
      repressor complex with Notch signaling induced hes1. Our findings are consistent
      with a role for FOXG1 in the inhibition of TGF-beta induced cytostasis in
      medulloblastoma.

PMID- 17522786
TI  - Neurointensive care management of raised intracranial pressure caused by severe
      valproic acid intoxication.
AB  - INTRODUCTION: We describe the neurointensive care (NIC) management of a patient
      with severe cerebral swelling and raised intracranial pressure (ICP) after severe
      sodium valproic acid (VPA) intoxication. A previously healthy 25-year old male
      with mild tonic-clonic epilepsy was found unconscious with serum VPA levels
      >10,000 micromol/l. The patient deteriorated to Glasgow Motor Scale score (GMS) 2
      and a CT scan showed signs of raised ICP. Early ICP was elevated, >50 mm Hg, and
      continuous EEG monitoring showed isoelectric readings. METHODS: The patient was
      treated with an ICP-guided protocol including mild hyperventilation,
      normovolemia, head elevation and intermittent doses of mannitol. Due to
      refractory elevations of ICP, high-dose pentobarbital infusion was initiated, and
      ICP gradually normalised. RESULTS: There were several systemic complications
      including coagulopathy, hypocalcemia and pancreatitis. The patient remained in a
      depressed level of consciousness for 2 months but gradually recovered, showing a
      good recovery with minor subjective cognitive deficits by 6 months. CONCLUSION:
      We conclude that NIC may be an important treatment option in cases of severe
      intoxication causing cerebral swelling.

PMID- 17522787
TI  - Vasospasm and cerebral infarction following isolated intraventricular hemorrhage.
AB  - INTRODUCTION: Cerebral arterial vasospasm following aneurysmal subarachnoid
      hemorrhage (SAH) is an important cause of delayed neurologic deterioration.
      Vasospasm following isolated intraventricular hemorrhage (IVH) is less common.
      Accepted predictors of vasospasm following SAH include poor Hunt-Hess grade,
      elevated transcranial Doppler velocities, and the thickness of cisternal blood on
      neuroimaging [1, 2]. The role of intraventricular hemorrhage in vasospasm is more
      controversial. METHODS: Case report and review of the literature. RESULTS: A 41
      year-old woman developed symptomatic delayed vasospasm 10 days following isolated
      IVH due to the rupture of an arteriovenous malformation (AVM). CONCLUSION:
      Intraventricular hemorrhage can independently cause significant delayed
      vasospasm. Possible mechanisms are described.

PMID- 17522788
TI  - Continuous intravenous NSAID administration for fever control.

PMID- 17522789
TI  - Continuous low dose diclofenac sodium infusion to control fever in neurosurgical
      critical care.
AB  - INTRODUCTION: Aim of this randomized prospective clinical trial is to compare two
      methods of antipyretics and evaluate their efficacy in controlling fever during
      the acute phase of brain damage. METHODS: Twenty-two febrile comatose patients:
      12 severe traumatic brain injury and 10 subarachnoid hemorrhage divided in 2
      groups: Diclofenac low-dose infusion (10 patients) and extemporaneous boluses of
      NSAIDs (CTRL, 12 patients). The primary outcome measure was length of time with
      temperature>38 degrees C. Secondary outcome measures were: 1) to assess the
      effects of each antipyretic strategy on intracranial pressure (ICP), cerebral
      perfusion pressure (CPP), mean arterial pressure (MAP) and heart rate; 2) to
      monitor adverse effects of each antipyretic strategy. The baseline
      characteristics in the two treatment groups were similar. RESULTS: Primary
      findings: percentage of time per patient with temperature>38 degrees C was
      significantly lower (P<0.0001) in the DCF group, 4% (0-22%), vs. 34% (8-56%) in
      CTRL group. In addition, mean T degrees , max T degrees were lower in DCF than in
      CTRL (P<0.05). Secondary findings: CPP and MAP were significantly higher in DCF
      group (P<0.05) while ICP was not different (NS). However, if ICP pre
      randomization was <25 mmHg, CTRL suffered a worst ICP (24+/-11 vs. 16+/-7
      P=0.01), MAP (89+/-10 vs. 104+/-10 P=0.01) and CPP (75+/-10 vs. 94+/-17 P=0.01)
      compared to DCF. No differences between the two treatment were recorded when
      ICP>or=25 mmHg before randomization. There was no gastrointestinal or
      intracranial bleeding. CONCLUSIONS: Low dose DCF infusion is a potential useful
      strategy for a successful control temperature better than intermittent NSAIDs
      dosing, minimizing potentially brain-damaging effects of fever.

PMID- 17522790
TI  - A pilot study of fibreoptic endoscopic evaluation of swallowing in patients with
      cuffed tracheostomies in neurological intensive care.
AB  - INTRODUCTION: Patients on neurological intensive care units (NICU) who require
      ventilatory support often suffer from co-existing bulbar dysfunction, either
      because of their underlying disease or because of their decreased level of
      consciousness. For this reason, most patients are ventilated through a cuffed
      tracheostomy tube, which allows a degree of protection from tracheal aspiration
      of saliva and gastric contents. Patients who are awake often complain of thirst,
      but traditionally are only offered oral fluids when the cuff of the tracheostomy
      tube has been deflated. Given that many patients in NICU cannot tolerate cuff
      deflation, a reliable technique is needed to assess the adequacy of the patient's
      swallow and therefore the risk of aspiration when the tracheostomy cuff is
      inflated. METHODS: The aim of this feasibility study was to examine the viability
      of Fibreoptic Endoscopic Evaluation of Swallowing (FEES) as a diagnostic tool to
      assess the effectiveness of swallowing in four NICU patients with cuffed
      tracheostomies. RESULTS: The technique was successful in all of the four
      patients. One patient was found to have a normal swallow. Two patients were seen
      to have laryngeal penetration of fluids and one patient aspirated the fluid
      challenge. CONCLUSION: This pilot study has demonstrated the feasibility of using
      the FEES technique for assessment of swallowing in patients with cuffed
      tracheostomy tubes; it therefore presents the prospect of allowing earlier
      drinking in such patients whilst helping confirm the safety of such a strategy.

PMID- 17522791
TI  - Clinical significance of serum S100B levels in neurointensive care.
AB  - OBJECTIVE: S100B is viewed as the most promising biomarker for brain damage. It
      has been proposed that this marker is useful in a Neurointensive Care Unit (NICU)
      as a monitoring parameter. This study aims to examine the clinical usefulness of
      daily serum S100B measurements in this setting. DESIGN: Prospective consecutive
      inclusion of patients. PATIENTS: A total of 79 patients with confirmed or
      suspected head injury or cerebrovascular insults (CVIs) (based upon patient
      history, computed tomography (CT) and/or magnetic resonance imaging (MRI) and
      neurological examination including coma scoring) who required neurointensive care
      were included in the study. INTERVENTIONS: Sampling for S100B was performed at
      admission and daily until patients were discharged from the NICU. S100B
      measurements were statistically compared to occurrence of secondary complications
      and outcome according to Glasgow Outcome Scale (GOS), with focus on clinical
      prediction. MEASUREMENTS AND MAIN RESULTS: 17 of 79 patients (22%) had secondary
      neurological complications. Mean S100B levels were found to be an independent
      parameter associated with these complications (P=0.03). Mean S100B levels were
      higher in patients with complications compared to those without on both the
      complication day (P=0.033) and the day after (P=0.015), but not the day prior to
      the complication (P=0.62). S100B did not predict secondary neurological
      complication. Neither mean (P=0.182) nor peak (P=0.370) S100B levels were
      associated with or predicted outcome according to dichotomised GOS. CONCLUSION:
      Daily S100B measurements are associated with secondary complications but not to
      outcome. However, daily S100B levels do not predict secondary complications,
      which limit the usefulness of this brain biomarker in this setting.

PMID- 17522792
TI  - Changes in intracranial pressure associated with chest physiotherapy.
AB  - INTRODUCTION: Management of intracranial hypertension is pivotal in the care of
      brain-injured patients. SUMMARY OF CASE: We report the case of a patient with
      both a closed head injury and anoxic encephalopathy, who subsequently experienced
      episodes of refractory intracranial hypertension. The patient's care was
      complicated by the development of a pneumonia, which required frequent turning of
      the patient and chest physiotherapy. Conventional wisdom suggests that these
      interventions may stimulate the patient and worsen intracranial pressure, and
      therefore should be avoided. RESULTS: Our observations on this patient, however,
      contradict this belief. This single-subject study presents data to support the
      use of chest physiotherapy in patients at risk for intracranial hypertension.
      CONCLUSIONS: Further, the evidence is compelling that a randomized-controlled
      trial is indicated to test the hypothesis that chest physiotherapy may actually
      result in short-term resolution of high intracranial pressure, and thus provide
      one more clinical tool in the management of elevated intracranial pressure.

PMID- 17522793
TI  - Role of intracranial pressure values and patterns in predicting outcome in
      traumatic brain injury: a systematic review.
AB  - INTRODUCTION: Raised intracranial pressure (ICP) has been consistently associated
      with poor neurological outcome. Our purpose was to systematically review the
      literature to estimate the association between ICP values and patterns and short-
      and long-term vital and neurological outcome. METHODS: Systematic review of
      studies identified from MEDLINE, EMBASE, and COCHRANE Registry search from 1966
      to 2005, and reference lists of identified articles, with independent assessment
      of methodological quality, population, ICP values and patterns, management of
      raised ICP and neurological outcomes. Summary odds ratios (OR) were calculated
      for the main outcomes using proportional odds models and logistic regression.
      RESULTS: Four prospective studies (409 patients) reported the effect of ICP
      values, and five studies (677 patients) reported the effect of ICP patterns on
      neurological outcome. No study reported neurological outcomes beyond 1 year.
      Relative to normal ICP (<20 mmHg), raised ICP was associated with elevated OR of
      death: 3.5 [95%CI: 1.7, 7.3] for ICP 20-40, and 6.9 [95%CI: 3.9, 12.4] for
      ICP>40. Raised but reducible ICP was associated with a 3-4-fold increase in the
      OR of death or poor neurological outcome. Refractory ICP pattern was associated
      with a dramatic increase in the relative risk of death (OR 114.3 [95%CI: 40.5,
      322.3]). CONCLUSIONS: Refractory ICP and response to treatment of raised ICP
      could be better predictors of neurological outcome than absolute ICP values.
      Limitations in the design of the studies analyzed precluded identification of the
      role of ICP monitoring in predicting short- and long-term outcomes.

PMID- 17522794
TI  - Endovascular treatment of inadvertent cannulation of the vertebro-subclavian
      arterial junction.
AB  - INTRODUCTION: Inadvertent arterial cannulation at a noncompressible site is a
      highly risky complication of central venous line placement. SUMMARY OF CASE: We
      present a case of inadvertent placement of a 6-French venous sheath into the
      right subclavian artery (SCA) at the origin of the vertebral artery (VA), which
      was treated successfully using endovascular therapy. RESULTS: Due to the complex
      site of cannulation, and the patient being fully anticoagulated, the use of a
      percutaneous closure device was not attempted. Open vascular surgery was not a
      treatment option due to high surgical risk. After determining left VA dominance,
      the right VA was occluded distal to the catheter entry point with platinum coils.
      Subsequently, a covered stent was placed into the SCA across the origin of the
      VA. The sheath was then removed safely without complications. A minor leak was
      initially present, which was stopped by repeating balloon inflation within the
      stent above nominal pressure.

PMID- 17522795
TI  - Successful intravenous thrombolysis in ischemic stroke caused by infective
      endocarditis.
AB  - INTRODUCTION: Infective endocarditis can lead to serious neurological
      complications including ischemic stroke and intracranial hemorrhage. Treatment
      with intravenous thrombolysis within 3 h of symptom onset has become the standard
      of care in acute ischemic stroke, but the safety and efficacy of this
      intervention in patients with infective endocarditis is unknown. SUMMARY OF CASE:
      We report the case of a patient with ischemic stroke who experienced substantial
      neurological improvement after being treated with intravenous thrombolysis (NIH
      stroke scale score of 15 on admission and 4 after treatment) and was subsequently
      found to have acute infective mitral endocarditis. CONCLUSION: Favorable response
      to thrombolysis may occur in patients with stroke due to infectious endocarditis.
      The safety of this therapy remains to be established.

PMID- 17522797
TI  - Management of recurrent cerebral arterial occlusion in a patient with cardiac
      decompensation.
AB  - We describe a woman with congestive heart failure who presented with acute
      cardiac decompensation followed by ischemic stroke. The management of the patient
      posed unique challenges for thrombolytic treatment (due to existing coagulopathy)
      and subsequent optimization of hemodynamic status. Issues related to rethrombosis
      and use of platelet glycoprotein IIB/IIIA inhibitors are also discussed.

PMID- 17522798
TI  - Neurocritical care mystery--pellets in the brain. Answer: droplets of Pantopaque
      contrast agent.

PMID- 17522796
TI  - Reliability of S100B in predicting severity of central nervous system injury.
AB  - S100B is a protein biomarker that reflects CNS injury. It can be measured in the
      CSF or serum with readily available immunoassay kits. The excellent sensitivity
      of S100B has enabled it to confirm the existence of subtle brain injury in
      patients with mild head trauma, strokes, and after successful resuscitation from
      cardiopulmonary arrest. The extent of S100B elevation has been found to be useful
      in predicting clinical outcome after brain injury. Elevations of S100B above
      certain threshold levels might be able to reliably predict brain death or
      mortality. A normal S100B level reliably predicts the absence of significant CNS
      injury. The specificity of S100B levels as a reflection of CNS injury is
      compromised by the findings that extra-cranial injuries can lead to elevations in
      the absence of brain injury. This potential problem can most likely be avoided by
      measuring serial S100B levels along with other biomarkers and carefully noting
      peripheral injuries. Serum markers GFAP and NSE are both more specific for CNS
      injury and have little to no extra-cranial sources. Sustained elevations of S100B
      over 24 h along with elevations of GFAP and NSE can more reliably predict the
      extent of brain injury and clinical outcomes. In the future, S100B measurements
      might reliably predict secondary brain injury and enable physicians to initiate
      therapeutic interventions in a timelier manner. S100B levels have been shown to
      rise hours to days before changes in ICP, neurological examinations, and
      neuroimaging tests. S100B levels may also be used to monitor the efficacy of
      treatments.

PMID- 17522799
TI  - Hypodense middle cerebral artery with fat embolus.
AB  - A 44-year-old man developed a right middle cerebral artery territory stroke due
      to a large fat embolism after an aortic valve repair. We briefly review the
      phenomenon of fat embolism and discuss the salient radiographic (CT) finding in
      this case--a "hypodense artery sign."

PMID- 17522800
TI  - Pharmacology and clinical use of recombinant activated factor seven in
      neurosciences.
AB  - Recombinant activated factor VII (rFVIIa, NovoSeven, NovoNordisc, Danemark) has
      been approved for the treatment of patients with hemophilia with inhibitors,
      further indications, at least in some countries, include the treatment of factor
      VII deficiency and Glanzmann thrombasthenia refractory to conventional therapy.
      Apart from these indications, the agent is increasingly used for the treatment of
      severe and potentially life-threatening bleeding manifestations, irrespective of
      the underlying hemostatic abnormality. The agent has successfully been used for
      the treatment of both inherited and acquired coagulopathies as well as
      thrombocytopathia or thrombocytopenia, however, most information on off-label use
      derives from case reports and retrospective studies and therefore publication
      bias can-not be excluded. In this review, we focus on the use of rFVIIa for the
      treatment of spontaneous and perioperative intracranial hemorrhage as well as
      trauma patients. We review the current knowledge regarding the physiology of
      hemostasis, the pharmacology of rFVIIa, and its clinical use in neurosciences.
      Further studies are urgently needed to define the efficacy and safety of
      recombinant activated factor VII in patients without hemophilia, factor VII
      deficiency, or Glanzmann thrombasthenia. At time, its use can be justified in
      life-threatening bleeding situations refractory to conventional treatment.

PMID- 17522802
TI  - Reference values for craniofacial structures in children 4 to 6 years old: review
      of the literature.
AB  - This review article addresses the question as to what methods can be used to
      investigate cranial structure and growth development in children 4 to 6 years
      old, and what the relevant reference values are for this age group. We screened
      the literature for epidemiological, longitudinal and cross-sectional studies
      investigating healthy children 4 to 6 years old without abnormalities and
      orthodontic therapy. Radiographic cephalometry is a practical, valid tool for
      analyzing craniofacial structure and growth processes. But it has several
      disadvantages, including the use of ionizing radiation, measuring points that are
      difficult to locate, no means of radiographic enlargement without distorting
      reference values, and the data's two-dimensionality. Anthropometry is another
      procedure for creating reference values for the craniofacial structure in
      children. Its advantages over radiographic cephalometry include three-dimensional
      results and no radiation exposure. Moreover, it yields precise and valid results
      for a wide variety of potential applications. In addition to these procedures,
      there are other techniques with which cranial structure and growth development in
      children 4 to 6 years old can be investigated. Those reported in the literature
      in this connection include standardized photographs, the creation of computerized
      and magnetic resonance images, and investigations performed on dry skulls. In
      short, there is great demand nowadays for investigations aimed at developing
      reference values for Caucasian children 4 to 6 years old. Radiographic
      cephalometry and anthropometry are two very common methods. Anthropometry is
      expected to become increasingly important because it involves no exposure to
      radiation.

PMID- 17522803
TI  - Vertical development of the cleft segments in infants with bilateral cleft lip
      and palate: effect of dentofacial orthopedic and surgical treatment on maxillary
      morphology from birth to the age of 11 months.
AB  - OBJECTIVE: The aim of this investigation was to use 3D (threedimensional)
      analysis of maxillary casts to document and graphically demonstrate the
      clinically-visible vertical deviation of the premaxilla and lateral segments from
      a defined reference plane, and to describe the effect of presurgical dentofacial
      orthopedic treatment and cleft lip operation. MATERIAL AND METHODS: The maxillary
      morphology of 17 infants with bilateral cleft lip and palate (investigation
      group) was examined by means of 3D cast measurement with a reflex microscope from
      the time of birth to the age of 11 months. All the patients were treated at the
      Dental Center of the University of Leipzig according to the same treatment
      approach [15], which in the first year of life entails the insertion of a
      modified palatal plate according to Hotz [17, 18], one-stage surgical repair of
      the cleft lip (at the age of 4-6 months on average), and closure of the hard and
      soft palates 6 months later. We selected the casts of 14 patients to use as the
      control group; they had been treated according to a different approach at, what
      at that time was, the Wolfgang Rosenthal Clinic for Plastic and Reconstructive
      Maxillofacial Surgery in Thallwitz. RESULTS: We observed vertical deviations of
      the cleft segments during the investigation period. Following surgical repair of
      the cleft lip, there was a caudal shift of the premaxilla in both groups that was
      cranially rotated before the operation. The investigation group also revealed a
      reduction in the vertical deviation of the lateral segments. We noted a
      harmonization in the position of the segments in the investigation group,
      however, this harmonization was not achieved in the control group.

PMID- 17522804
TI  - Cephalometric assessment of the axial inclination of upper and lower incisors in
      relation to the third-order angle.
AB  - BACKGROUND AND AIM: Estimating incisor inclination cephalometrically by reference
      lines NA and NB puts the orthodontist in the difficult position of relating these
      axial inclination data to the bracket's third-order prescription which refers to
      a perpendicular to the occlusal plane. Purpose of the present study was to
      evaluate the relationship between the cephalometrically-assessed incisor
      inclination (using the lines NA and NB for reference) and the third-order angle
      (syn.: torque angle, TA) according to Andrews' description, and moreover to
      investigate the correlation between incisor inclination data and skeletal
      sagittal and skeletal-vertical findings. MATERIALS AND METHODS: The lateral
      cephalograms and corresponding dental casts of 67 subjects between 10 and 25
      years of age (regardless of skeletal and dental relationships) were considered in
      the study. All subjects were Caucasian, and none had undergone orthodontic
      therapy. Upper (U1) and lower (L1) incisor angulations were cephalometrically
      assessed in reference to the NA and NB lines and compared to third-order angles
      obtained from dental cast measurements with an incisor inclination-recording
      appliance. Incisor inclination data from the two measurements were correlated to
      craniofacial sagittal (angles SNA, SNB, ANB) and vertical (angles NSL-NL, NSL-ML,
      ML-NL) findings from the radiographs. RESULTS: The third-order angles in the
      upper arch measured on the dental casts were a mean of 16.2 degrees (SD = 5.3
      degrees) smaller than the axial inclination according to the NA line; the lower
      incisor third-order data were less than those of the axial inclination according
      to the NB line by a mean of 27.8 degrees (SD = 4.75 degrees). In this sample,
      there was a range of 42.7 degrees for the U1TA variable (mean = 5.6 degrees, SD
      9.73 degrees) and 47 degrees for U1NA/ degrees variable (mean = 21.71 degrees, SD
      = 8.67 degrees). The L1TA variable showed a range of 29 degrees (mean = -2.95
      degrees, SD = 7.17 degrees), the radiographic L1NB/ degrees range was 23 degrees
      (mean = 24.91 degrees, SD = 5.8 degrees). We observed a highly significant
      correlation (r(NA) = 0.84***, r(NB) = 0.76***) between the Andrews' angle and the
      inclination estimated in reference to the NA and NB lines. No significant
      correlation between incisor inclination and craniofacial measurements was
      detected. CONCLUSIONS: Dental cast measurements seem to be more precise and more
      valid than lateral radiographs. The method we describe enables clinicians to get
      a good idea precisely and quickly of how much torque potential remains in the
      brackets and archwires during treatment. The inclination of the incisors can also
      be calculated using the regression equations provided, making additional lateral
      cephalograms unnecessary.

PMID- 17522805
TI  - Evaluation of vertical parameters in cephalometry.
AB  - AIM: The aim of this study was to determine the validity of different vertical
      parameters in cephalometry. MATERIALS AND METHODS: The cephalograms of 94
      patients were used in this study. The inclusion criteria were as follows:
      skeletal Class I, completion of maximum skeletal growth, and no history of
      orthodontic therapy. The control group consisted of 34 subjects with very good
      occlusion (overbite 2-4 mm). The patients were classified with the help of dental
      casts: Group 1 (n = 31) patients with cover-bite (overbite > 5.5 mm) and Group 2
      (n = 29) patients with anterior open bite (overbite < -0.5 mm). In addition to
      the 24 standard cephalometric measurements (Bergen-Analysis), we included
      individualized norm values (Segner & Hasund), the Overbite Depth Indicator (ODI)
      described by Kim, the Denture Frame Analysis (DFA) described by Sato, and facial
      type evaluations according to Schopf. RESULTS: We observed significant
      differences among the three study groups in all the vertical parameters tested.
      We demonstrated statistically-significant classification results for the Segner &
      Hasund harmony box's individualized norm values (83.8%), and those of the ODI
      (77.7%) and ML-AB angle (76.6%). CONCLUSIONS: Based on the vertical cephalometric
      parameters, we succeeded in statistically differentiating among the groups with
      open bite, cover-bite and the control group. Various measurements must be taken
      to ensure that the cephalometric vertical relationships are reliably evaluated.

PMID- 17522806
TI  - A Comparison of the periodontal health of patients during treatment with the
      Invisalign system and with fixed lingual appliances.
AB  - OBJECTIVE: Evaluation of the periodontal health of patients during treatment with
      the Invisalign system or fixed lingual appliances. STUDY DESIGN: The study was
      designed as a concomitant trial of two groups of consecutive patients. The
      lingual patients were evaluated between February and May 2005. PATIENTS AND
      METHODS: Thirty patients each with aligners or fixed lingual appliances were
      examined at three consecutive control visits for their periodontal status. All
      the Invisalign patients and some of those wearing lingual appliances were
      patients from the Department of Orthodontics and Dentofacial Orthopedics of the
      Charite Berlin. The rest were recruited from the practices of two licensed
      orthodontists. The patients' periodontal health was evaluated in reference to a
      modified Gingiva, modified Plaque and modified Papillary Bleeding Index; we also
      measured the sulcus probing depth. All indices were documented buccally in the
      1st and 3rd quadrants, and lingually in the 2nd and 4th quadrants from central
      incisor to first molar. The sulcus probing depth was measured mesially, distally,
      buccally and lingually in each quadrant's first molar and first premolar. Each
      control visit was concluded with detailed, individualized instructions in oral
      hygiene. RESULTS: Overall, the Invisalign patients demonstrated significantly
      better modified indices. However, the sulcus probing depths were very similar in
      both treatment groups. CONCLUSION: Although all the teeth and parts of the
      keratinized gingiva are covered nearly all day during Invisalign treatment, the
      periodontal risk is lower than that associated with fixed lingual appliances.
      This may be due to the fact that aligners are removable, permitting unimpeded
      oral hygiene. In contrast, the lingual tooth surfaces are very difficult to clean
      when fitted with a fixed appliance.

PMID- 17522807
TI  - Changes in gingival recession related to orthodontic treatment of traumatic deep
      bites in adults.
AB  - INTRODUCTION: It was the aim of this investigation to establish whether
      orthodontic treatment of traumatic deep bites can restore trauma-related gingival
      recessions in adults. SUBJECTS AND METHODS: Forty-one incisor sites with trauma
      related recession (group Tr) and 54 trauma-free sites (group NonTr) were
      diagnosed in the upper palatal or lower buccal regions in twelve adult patients
      (mean age 38.3 +/- 8.1 years). The 48 antagonistic sites on the buccal aspects of
      the upper incisors (Ubuc) and 47 sites on the lingual aspects of the lower
      incisors (L-ling) were also evaluated. Changes in clinical crown lengths achieved
      during treatment were measured on dental casts, and length changes in recessions
      were measured on screen projections of magnified intraoral photographs. RESULTS:
      The clinical crown lengths (mean: -1.13 +/- 0.97 mm) and recession depths (mean: 
      2.05 +/- 0.93 mm) decreased significantly (p < 0.001) in the trauma group (Tr).
      We also observed significant shortening (p < 0.05) of clinical crown lengths in
      the buccal sites of upper incisors (U-buc) (mean: -0.16 +/- 0.46 mm). All other
      changes were insignificant. CONCLUSIONS: Orthodontic treatment of traumatic deep
      bites involving removal of gingival trauma and intrusion of incisor teeth shows
      great potential in reducing the length of clinical crowns and depth of gingival
      recessions. In trauma-free buccal sites of upper incisors, intrusion therapy may
      also improve the gingival marginal contour.

PMID- 17522808
TI  - Stability following combined orthodontic-surgical treatment for skeletal anterior
      open bite - a cephalometric 15-year follow-up study.
AB  - OBJECTIVE: The aim of the present study was to evaluate the long-term skeletal
      and dento-alveolar stability 15 years after combined orthodontic and surgical
      correction of skeletal anterior open bite. PATIENTS AND METHODS: Ten (8 female, 2
      male) anterior openbite patients who had undergone orthodontic treatment in
      combination with bimaxillary surgery at Hanover Medical School were examined.
      Each patient had undergone Le Fort I osteotomy combined with bilateral sagittal
      split osteotomy (BSSO); osteosynthesis with plates and screws was carried out in
      the maxilla, and wire-osteosynthesis in the mandible. Cephalometric records of
      these patients were examined immediately before the start of the orthodontic
      treatment (T1), before surgery (T2), immediately after surgery (T3), medium-term
      after surgery, averaging 1.5 years (T4), and long-term after surgery, averaging
      15 years (T5). Hasund cephalometric analysis was performed for which skeletal and
      dental cephalometric measurements had been taken. RESULTS: Moderate skeletal
      relapse was observed 15 years after surgery. Overbite remained quite stable 15
      years after surgery, which is mainly due to the upper and lower incisors'
      eruption over the long-term period. CONCLUSION: Treatment of skeletal open bite
      via Le Fort I and bilateral sagittal split osteotomy appears to be a clinically
      successful procedure providing stable results.

PMID- 17522809
TI  - Adjuvant arthritis 50 years on: The impact of the 1956 article by C. M. Pearson,
      'Development of arthritis, periarthritis and periostitis in rats given
      adjuvants'.
AB  - The Science Citation Index (Web of Science) has now accumulated over 700
      citations to this report published in Proc Soc exp Biol Med 1956; 91: 95-101,
      including several in 2006. This memoire is a tribute to its author for revealing
      the opportunities for so much subsequent research in experimental pharmacology
      and toxicology. For half a century, the adjuvant disease in rats has enormously
      aided research on drugs to control arthritis and other chronic inflammatory
      disorders. The adjuvant also triggers many systemic responses beyond the
      articular tissues. So we are given simultaneously a window to explore the
      converse phenomenon: namely, how a chronic disease can affect drug efficacy and
      toxicity. This phenomenon has been variously described as patho-pharmacodynamics,
      conditional pharmacology/toxicology and 'a right nuisance' ! Nevertheless it has
      enormous heuristic value for clinical therapeutics.

PMID- 17522810
TI  - Effect of acute and repeated administration of paracetamol on opioidergic and
      serotonergic systems in rats.
AB  - OBJECTIVE AND DESIGN: We investigated the antinociceptive effect of paracetamol
      or morphine after repeated administration and the changes in the characteristics
      of central mu-, kappa- and 5-HT2 receptors. TREATMENT: Male rats were injected
      twice a day for seven days with paracetamol (400 mg/kg, i. p.) or morphine (5
      mg/kg, s. c.). METHODS: The antinociceptive effect was evaluated 30 min after
      single and multiple doses of paracetamol and morphine through the hot-plate test.
      Binding techniques were used to evaluate the receptor characteristics in the
      frontal cortex. RESULTS: Both paracetamol and morphine induced an antinociceptive
      effect on day 1 but only paracetamol maintained this effect for seven days while
      morphine did not. The number of mu-opioid receptors decreased on days 1, 3, and 7
      by a similar percentage after paracetamol administration (by 29, 31 and 34 %,
      respectively), while morphine produced a progressive decrease in comparison with
      controls (by 37, 49 and 60 %, respectively) and kappa-opioid receptors were
      unaffected. Both drugs similarly decreased the 5-HT2 receptor number on all days
      of treatment (by about 30 %). CONCLUSIONS: The opioidergic and serotonergic
      systems are involved in different ways in the induction and maintenance of
      antinociception after paracetamol or morphine treatment.

PMID- 17522811
TI  - Peripheral blood mononuclear cell proliferative responses to soluble and
      particulate heat shock protein 65 in health and inflammatory bowel disease.
AB  - OBJECTIVES: The aims of this study were to determine, in peripheral blood
      mononuclear cells (PBMC), whether particulate antigen triggers (i) an amplified
      cell proliferative response compared to soluble antigen and (ii) a dysfunctional
      response in cells derived from patients with chronic inflammation and
      specifically in those with inflammatory bowel disease (IBD). SUBJECTS: Healthy
      volunteers (n = 17), inflammatory controls (n = 8) and patients with IBD (n = 17)
      were recruited from St Thomas' and Guys' Hospital, London, UK. METHODS: Following
      optimisation of experimental conditions (0.1-10.0 mug/ml antigen), PBMC were
      stimulated with (i) 10.0 mug/ml recombinant soluble heat shock protein 65 (hsp
      65) and (ii) 1.0 and 10.0 mug/ml hsp 65 conjugated to microparticles (0.5 mum
      diameter). PBMC proliferative responses were measured by (3)H-Thymidine
      incorporation at day 5 and results compared between groups using unpaired t-test.
      RESULTS: Conjugation to microparticles of low dose hsp 65 significantly increased
      overall proliferative responses by 2-11 fold compared to soluble antigen alone (p
      < 0.05). However, no specific PBMC proliferative dysregulation was noted in cells
      from subjects with IBD. CONCLUSIONS: Low dose antigen, in microparticulate form,
      leads to amplified cell proliferation in primary human cells, as showed
      previously in cell lines and animal studies. However there is no abnormal
      proliferative response in cells from subjects with IBD.

PMID- 17522812
TI  - Ketamine inhibits polymorphonuclear leucocyte CD11b expression and respiratory
      burst activity in endotoxemic rats.
AB  - OBJECTIVE AND DESIGN: To observe the effect of ketamine on polymorphonuclear
      leucocytes (PMN) adhesion and respiratory burst activity in endotoxemia rats.
      MATERIALS: 30 rats were randomly allocated to five groups: rats challenged with
      intraperitoneal injection of saline (saline group); challenged with
      intraperitoneal injection of LPS 10 mg/kg (LPS group); challenged with
      intraperitoneal injection of LPS 10 mg/kg and treated by intraperitoneal
      injection of ketamine 5, 25, 50 mg/kg at 0, 1, 2, 3, 4, 5 h after the injection
      of LPS, respectively (three ketamine treatment groups). METHODS: PMN respiratory
      burst and CD11b expression were measured with flow cytometry at the end of 1 h, 4
      h, and 6 h. RESULTS: LPS challenge significantly increased PMN respiratory burst
      activity and CD11b expression when compared with the saline group (p < 0.01).
      There was a significant decrease in LPS-induced PMN respiratory burst activity
      and CD11b expression in three ketamine treatment groups when compared with LPS
      group (p < 0.01). CONCLUSIONS: Ketamine significantly inhibits PMN CD11b
      expression and respiratory burst activity in endotoxemic rats.

PMID- 17522813
TI  - Endotoxin-induced activation of equine platelets: evidence for direct activation
      of p38 MAPK pathways and vasoactive mediator production.
AB  - OBJECTIVE AND DESIGN: The aim of this study was to determine the effects of
      endotoxin on p38 MAPK activation in equine platelets and leukocytes in vivo and
      in vitro and its role in thromboxane (Tx) production with reference to equine
      endotoxaemia. METHODS: Six adult Thoroughbred horses were used for in vivo
      infusion studies and separate in vitro studies. For in vivo studies, following
      collection of a pre-infusion sample, horses were infused with E. Coli O55:B5 LPS
      (30 ng/kg; 30 min) during and after which platelets were harvested. For in vitro
      studies isolated platelets and leukocytes were exposed to LPS (10 pg/ml-1
      microg/ml). p38 MAPK activity was assessed by SDS-PAGE followed by
      immunoblotting. TxA2 release was measured by radioimmunoassay. RESULTS: LPS
      infusion caused increased phospho-p38 MAPK in equine platelets and leukocytes
      (1492 +/- 486 % and 83 +/- 45 above basal, respectively) from 10 min after the
      start of the infusion, which returned to basal by 60 min. In vitro, platelets
      were 1,000 times more sensitive to LPS than leukocytes in terms of both TxA2
      production (EC50 66 pg/ml versus 110 ng/ml, respectively) and p38 MAPK
      phosphorylation (EC50 11.1 +/- 2 pg/ml versus 14.8 +/- 4 ng/ml, respectively).
      p38 MAPK inhibitors SB203580 and PD169316 attenuated LPS-induced TxA2 release in
      platelets, but not leukocytes. CONCLUSIONS: In vivo, LPS stimulates TxA2
      production and p38 MAPK phosphorylation in equine platelets and leukocytes at a
      concentration within a similar range to those reported in clinical endotoxaemia.
      These data suggest that LPS-induced eicosanoid production in the early phase of
      clinical endotoxaemia may involve direct effects of LPS upon platelets, mediated
      via activation of p38 MAPK.

PMID- 17522814
TI  - HMGB1 modulates inflammatory responses in LPS-activated macrophages.
AB  - OBJECTIVE: As a late mediator of inflammation, high mobility group box 1 protein
      (HMGB1) amplifies the inflammatory responses to tissue injury and infection by
      inducing and extending the production of proinflammaory cytokines. The aim was to
      investigate whether HMGB1 mediates such effects by affecting the production of
      anti-inflammatory mediators. MATERIALS AND METHODS: The murine macrophage RAW
      264.7 cells were stimulated with 0.5 microg/ml of LPS and the levels of HMGB1,
      TNFalpha, IL-1beta, IL-10 and TGF-beta1 in the culture supernatants were measured
      by ELISA. Also, the mRNA expression for IL-10 and TGF-beta1 was assessed by RT
      PCR. RESULTS: LPS induced HMGB1 release at 8 h and reached a peak at 48 h.
      Significant (p < 0.05) production of TNFalpha, IL-1beta, IL-10, and TGF-beta1 was
      seen after 8 h. However, while the levels of TNFalpha and IL-beta remained
      elevated, IL-10 and TGF-beta1 release markedly declined by 24 h after
      stimulation. When cells were stimulated in the presence of conditioned medium
      derived from a 24 h LPS-stimulated culture, the production of TNFalpha and IL
      1beta was increased while IL-10 and TGF-beta1 release and mRNA transcripts were
      decreased. A neutralizing anti-HMGB1 antibody added to the conditioned media
      reveresed these responses. CONCLUSIONS: HMGB1 modulates the inflammatory cascade
      in activated macrophages by inducing proinflammatory, while suppressing anti
      inflammatory responses.

PMID- 17522816
TI  - Zymomonas mobilis for fuel ethanol and higher value products.
AB  - High oil prices, increasing focus on renewable carbohydrate-based feedstocks for
      fuels and chemicals, and the recent publication of its genome sequence, have
      provided continuing stimulus for studies on Zymomonas mobilis. However, despite
      its apparent advantages of higher yields and faster specific rates when compared
      to yeasts, no commercial scale fermentations currently exist which use Z. mobilis
      for the manufacture of fuel ethanol. This may change with the recent announcement
      of a Dupont/Broin partnership to develop a process for conversion of
      lignocellulosic residues, such as corn stover, to fuel ethanol using recombinant
      strains of Z. mobilis. The research leading to the construction of these strains,
      and their fermentation characteristics, are described in the present review. The
      review also addresses opportunities offered by Z. mobilis for higher value
      products through its metabolic engineering and use of specific high activity
      enzymes.

PMID- 17522815
TI  - Modified skin window technique for the extended characterisation of acute
      inflammation in humans.
AB  - OBJECTIVE: To modify the skin window technique for extended analysis of acute
      inflammatory responses in humans, and demonstrate its applicability for
      investigating disease. SUBJECTS: 15 healthy subjects and 5 Crohn's patients.
      TREATMENT: Skin windows, created by dermal abrasion, were overlaid for various
      durations with filter papers saturated in saline, 100 ng/ml muramyl dipeptide
      (MDP) or 10 microg/ml interleukin-8 (IL-8). METHODS: Exuded leukocytes were
      analyzed by microscopy, immunoblot, DNA-bound transcription factor arrays and RT
      PCR. Inflammatory mediators were quantified by ELISA. RESULTS: Infiltrating
      leukocytes were predominantly neutrophils. Numerous secreted mediators were
      detectable. MDP and IL-8 enhanced responses. Many signalling proteins were
      phosphorylated with differential patterns in Crohn's patients, notably PKC
      alpha/beta hyperphosphorylation (11.3 +/- 3.1 vs 1.2 +/- 0.9 units, P < 0.02).
      Activities of 44 transcription factors were detectable, and sufficient RNA
      isolated for expression analysis of over 400 genes. CONCLUSIONS: The
      modifications enable broad characterisation of inflammatory responses and
      administration of exogenous immunomodulators.

PMID- 17522817
TI  - The gap between science and perception: the case of plant biotechnology in
      Europe.
AB  - Although the global area of biotech crops continues to climb for the tenth
      consecutive year at a sustainable double-digit growth rate, the acceptance of
      biotech products from agriculture in Europe is still low. There is a gap between
      science and perception. It is a strong belief that the public turning against
      science and against GM food has been encouraged by the negative activities of NGO
      groups. Scientists have to overcome the purely risk-based discussion, and the
      benefits of plant biotechnology have to be made literally visible. GM food should
      be available, the benefits should be tangible and the consumer should have fun
      with such novel food. The gap could be reduced if genetically modified plants and
      the products thereof were regulated in the same way as classical products.

PMID- 17522818
TI  - Biotechnology patenting policy in the European Union--as exemplified by the
      development in Germany.
AB  - Patenting of biotechnological inventions is an important concomitant side effect
      of progress in this field, but also a matter of dispute in the public. In this
      paper, the significance of and the prerequisites for patenting are reviewed, and
      the principal requirements for biotechnology patents in the signatory states of
      the European Patent Convention (EPC) are summarized. This is followed by a report
      on the historical development of biotech-patent legislation in Europe and in
      Germany as one contracting state to EPC and member state of the European Union.
      Characteristic features of the patenting policy in Europe and Germany are
      illustrated by critical examples of biotechnology patents or patent applications.
      Some examples illustrate the influence of the European Union's national states'
      case laws after these had crystallized into the EU Biotechnology Directive
      (1998), which later was adopted by the European Patent Organization into its
      Implementing Regulations (2001) and was implemented into national patent acts.
      Some frequent objections against patenting in modern biotechnology are
      considered. More and better information about prerequisites, consequences, and
      opportunities of patenting in biotechnology, if conveyed to science and
      technology scholars as multipliers, may help to rationalize public discussion.

PMID- 17522819
TI  - Bioscience, bioinnovations, and bioethics.
AB  - Biosciences and their applications, which we call biotechnology, have affected
      human society in many ways. Great hopes have been set on future biotechnology.
      The future depends on three key issues. First, we need good science. Recent
      developments in biosciences have surprised us in many ways. I shall explain in
      this article how. Secondly, we need structured innovation systems in order to
      commercialize our discoveries. Europe is slow in this respect compared to our
      Japanese and American competitors and may lose in the competition. I shall
      describe the Finnish innovation chain using the rewarded Otaniemi model as an
      example of how commercialization can be done in a systematic way. Thirdly, we
      need norms to guide what to do and where to go. Bioethics is probably the most
      neglected of the three key issues. With modern biotechnology we are able to do
      things that should worry every citizen, but the ethical discussion has been
      largely neglected or the discussion in our pluralistic society is leading
      nowhere. I shall finally discuss these problems from a historical perspective.

PMID- 17522820
TI  - Genetically modified organisms in the United States: implementation, concerns,
      and public perception.
AB  - We examine the state of biotechnology with respect to genetically modified (GM)
      organisms in agriculture. Our focus is on the USA, where there has been
      significant progress and implementation but where, to date, the matter has drawn
      little attention. GM organisms are the result of lateral gene transfers, the
      transfer of genes from one species to another, or sometimes, from one kingdom to
      another. The introduction of foreign genes makes some people very uncomfortable,
      and a small group of activists have grave concerns about the technology. Attempts
      by activists to build concern in the general public have garnered little
      attention; however, the producers of GM organisms have responded to their
      concerns and established extensive testing programs to be applied to each
      candidate organism that is produced. In the meantime, GM varieties of corn,
      cotton, soybean and rapeseed have been put into agricultural production and are
      now extensively planted. These crops, and the other, newer GM crops, have
      produced no problems and have pioneered a silent agricultural revolution in the
      USA.

PMID- 17522821
TI  - Agricultural biotechnology and its contribution to the global knowledge economy.
AB  - The theory of neoclassical welfare economics largely shaped international and
      national agricultural policies during the Cold War period. It treated technology
      as an exogenous factor that could boost agricultural productivity but not
      necessarily sustainable agriculture. New growth theory, the economic theory of
      the new knowledge economy, treats technological change as endogenous and argues
      that intangible assets such as human capital and knowledge are the drivers of
      sustainable economic development. In this context, the combined use of
      agricultural biotechnology and information technology has a great potential, not
      just to boost economic growth but also to empower people in developing countries
      and improve the sustainable management of natural resources. This article
      outlines the major ideas behind new growth theory and explains why agricultural
      economists and agricultural policy-makers still tend to stick to old welfare
      economics. Finally, the article uses the case of the Cassava Biotechnology
      Network (CBN) to illustrate an example of how new growth theory can be applied in
      the fight against poverty. CBN is a successful interdisciplinary crop research
      network that makes use of the new knowledge economy to produce new goods that
      empower the poor and improve the productivity and nutritional quality of cassava.
      It shows that the potential benefits of agricultural biotechnology go far beyond
      the already known productivity increases and pesticide use reductions of existing
      GM crops.

PMID- 17522822
TI  - Exploration and Swiss field-testing of a viral gene for specific quantitative
      resistance against smuts and bunts in wheat.
AB  - The viral gene for the killer protein 4 (KP4) has been explored for its
      antifungal effect in genetically modified wheat to defeat specifically the seed
      transmitted smut and bunt diseases. In vitro both important seed-transmitted
      diseases of wheat, loose smut (Ustilago tritici) and stinking smut (Tilletia
      caries), are susceptible to KP4, whereas all other organisms tested so far proved
      to be not susceptible to KP4. For studies in planta we used stinking smut as a
      model fungus. In greenhouse experiments, two KP4-transgenic wheat lines showed up
      to 30% lower symptom development as compared to the nontransgenic control. As the
      last step in the proof of concept, field-testing has shown for the first time
      increased fungal resistance of a transgene in wheat. Due to its specificity
      against smuts and bunts, KP4 presents a very low risk to humans and the
      environment. Field-testing in Switzerland is regulated by a strong law, which for
      research is acceptable if legally and scientifically correctly applied.

PMID- 17522823
TI  - Recombinant DNA technology in apple.
AB  - This review summarizes the achievements of almost 20 years of recombinant DNA
      technology applied to apple, grouping the research results into the sections:
      developing the technology, insect resistance, fungal disease resistance, self
      incompatibility, herbicide resistance, fire blight resistance, fruit ripening,
      allergens, rooting ability, and acceptance and risk assessment. The diseases fire
      blight, caused by Erwinia amylovora, and scab, caused by Venturia inaequalis,
      were and still are the prime targets. Shelf life improvement and rooting ability
      of rootstocks are also relevant research areas. The tools to create genetically
      modified apples of added value to producers, consumers, and the environment are
      now available.

PMID- 17522824
TI  - Prospects for biopolymer production in plants.
AB  - It is likely that during this century polymers based on renewable materials will
      gradually replace industrial polymers based on petrochemicals. This chapter gives
      an overview of the current status of research on plant biopolymers that are used
      as a material in non-food applications. We cover technical and scientific
      bottlenecks in the production of novel or improved materials, and the potential
      of using transgenic or alternative crops in overcoming these bottlenecks. Four
      classes of biopolymers will be discussed: starch, proteins, natural rubber, and
      poly-beta-hydroxyalkanoates. Renewable polymers produced by chemical
      polymerization of monomers derived from sugars, vegetable oil, or proteins, are
      not considered here.

PMID- 17522825
TI  - Plastoglobule lipid bodies: their functions in chloroplasts and their potential
      for applications.
AB  - Plastoglobules are plant lipid bodies localized inside plastids. They have long
      been considered as mere lipid storage compartments. However, ultrastructural and
      proteomic data now suggest their involvement in various metabolic pathways,
      notably the biosynthesis of tocopherols. In this work, the current knowledge on
      the structure and functions of plastoglobules is reviewed. On the basis of
      similarities between plastoglobules and seed oleosomes, the potential of
      plastoglobules for bioengineering applications is discussed.

PMID- 17522826
TI  - Genetic and ecological consequences of transgene flow to the wild flora.
AB  - Gene flow from crops to wild relatives by sexual reproduction is one of the major
      issues in risk assessment for the cultivation of genetically engineered (GE)
      plants. The main factors which influence hybridization and introgression, the two
      processes of gene flow, as well as the accompanying containment measures of the
      transgene, are reviewed. The comparison of risks between Switzerland and Europe
      highlights the importance of regional studies. Differences were assessed for
      barley, beet and wheat. Moreover, transgene flow through several wild species
      acting as bridge (bridge species) has been up to now poorly investigated. Indeed,
      transgene flow may go beyond the closest wild relative, as in nature several wild
      species complexes hybridize. Its importance is assessed by several examples in
      Poaceae. Finally, the transgene itself has genetic and ecological consequences
      that are reviewed. Transgenic hybrids between crops and wild relatives may have
      lower fitness than the wild relatives, but in several cases, no cost was
      detected. On the other hand, the transgene provides advantages to the hybrids, in
      the case of selective value as a Bt transgene in the presence of herbivores.
      Genetic and ecological consequences of a transgene in a wild species are complex
      and depend on the type of transgene, its insertion site, the density of plants
      and ecological factors. More studies are needed for understanding the short and
      long term consequences of escape of a transgene in the wild.

PMID- 17522827
TI  - Assessing effects of transgenic crops on soil microbial communities.
AB  - Deleterious effects of transgenic plants on soils represent an often expressed
      concern, which has catalyzed numerous studies in the recent past. In this
      literature review, studies addressing this question have been compiled. A total
      of 60 studies has been found, and their findings as well as their analytical
      approaches are summarized. These studies analyzed the effects of seven different
      types of genetically engineered traits, i.e., herbicide tolerance, insect
      resistance, virus resistance, proteinase inhibitors, antimicrobial activity,
      environmental application, and biomolecule production. Sixteen genetically
      engineered plant species were investigated in these studies including corn,
      canola, soybean, cotton, potato, tobacco, alfalfa, wheat, rice, tomato, papaya,
      aubergine, and silver birch. Many of these plants and traits have not been
      commercialized and represent experimental model systems. Effects on soil
      microbial characteristics have been described in various studies, indicating the
      sensitivity and feasibility of the analytical approaches applied. However,
      classification of the observed effects into acceptable and unacceptable ones has
      not been possible so far. Establishment of validated indicators for adverse
      effects represents a scientific challenge for the near future, and will assist
      risk assessment and regulation of transgenic plants commercially released to the
      field.

PMID- 17522828
TI  - Ecological impacts of genetically modified crops: ten years of field research and
      commercial cultivation.
AB  - The worldwide commercial cultivation of genetically modified (GM) crops has
      raised concerns about potential adverse effects on the environment resulting from
      the use of these crops. Consequently, the risks of GM crops for the environment,
      and especially for biodiversity, have been extensively assessed before and during
      their commercial cultivation. Substantial scientific data on the environmental
      effects of the currently commercialized GM crops are available today. We have
      reviewed this scientific knowledge derived from the past 10 years of worldwide
      experimental field research and commercial cultivation. The review focuses on the
      currently commercially available GM crops that could be relevant for agriculture
      in Western and Central Europe (i.e., maize, oilseed rape, and soybean), and on
      the two main GM traits that are currently commercialized, herbicide tolerance
      (HT) and insect resistance (IR). The sources of information included peer
      reviewed scientific journals, scientific books, reports from regions with
      extensive GM crop cultivation, as well as reports from international governmental
      organizations. The data available so far provide no scientific evidence that the
      cultivation of the presently commercialized GM crops has caused environmental
      harm. Nevertheless, a number of issues related to the interpretation of
      scientific data on effects of GM crops on the environment are debated
      controversially. The present review highlights these scientific debates and
      discusses the effects of GM crop cultivation on the environment considering the
      impacts caused by cultivation practices of modern agricultural systems.

PMID- 17522829
TI  - [Preoperative evaluation of the bleeding history. Recommendations of the working
      group on perioperative coagulation of the Austrian Society for Anaesthesia,
      Resuscitation and Intensive Care].
AB  - Unexpected bleeding in the perioperative period is largely caused by impaired
      inherited or drug-induced primary haemostasis. Standard tests for plasma
      coagulation are predominantly employed to gauge the risk of bleeding. In
      accordance with several reports the subcommittee for perioperative coagulation
      (AGPG) of the Austrian Society of Anaesthesia, Resuscitation and Intensive Care
      (OGARI) recommends the use of a standardised questionnaire to detect an increased
      risk of bleeding. Accordingly, healthy patients of the American Society of
      Anesthesiologists (ASA) grades I and II without any suspicion of impaired
      haemostasis who are scheduled for procedures without expected transfusion
      requirements, need no standard tests for coagulation. In all other patients
      (including patients taking medication affecting coagulation, or patients who are
      unable to provide adequate information) platelet count, platelet function, aPTT,
      PT, and fibrinogen levels should be assessed.

PMID- 17522830
TI  - [The new regulations for the licence to practice medicine. Implementation for the
      faculty of anesthesiology at the University Clinic Hamburg-Eppendorf].
AB  - After the amendments to the regulations for the licence to practice medicine, the
      rating of the faculty of anesthesiology has clearly increased. In the following
      article a concept will be described whereby these standards were implemented at
      the University of Hamburg. The basic principle, especially the training in the
      practical proficiencies, is to achieve a continuous learning process from
      students through to specialists for anesthesiology.

PMID- 17522831
TI  - [Photodynamic therapy of cutaneous epithelial malignancies. An evidence-based
      review].
AB  - During the last years photodynamic therapy (PDT) has progressively established
      itself as a standard treatment for non-melanoma skin cancer. A number of clinical
      studies have demonstrated its efficacy--also compared to other treatment
      modalities--as well as good acceptance by patients and outstanding cosmetic
      results. For Bowen disease and superficial basal cell carcinoma, PDT can be
      regarded as the first-line non-invasive treatment. In the treatment of actinic
      keratoses PDT should be considered when cosmesis is crucial or in cases of field
      cancerization. In nodular basal cell carcinoma, effectiveness for lesions up to a
      thickness of 2 mm is well documented. In summary the evidence level seems
      sufficient to regard PDT as valuable treatment modality of which patients should
      not be deprived.

PMID- 17522833
TI  - "Transcribing" postischemic neurogenesis: a tale revealing hopes of adult brain
      repair.

PMID- 17522832
TI  - Turning back the clock: regression of abdominal aortic aneurysms via
      pharmacotherapy.
AB  - Abdominal aortic aneurysm (AAA) is a common disease that causes progressive
      expansion and rupture of the aorta with high mortality. There is a large and
      unmet need for nonsurgical treatment for AAA. Research has shown that an
      intricate network of inflammatory cells and interstitial cells contributes to the
      formation of AAA by producing pro-inflammatory mediators that activate enzymes to
      degrade the extracellular matrix (ECM) and impair ECM biosynthesis.
      Pharmacological agents such as statins and angiotensin-converting enzyme
      inhibitors may promote tissue stabilization in AAA by diminishing pro
      inflammatory signaling and normalizing metabolism of the ECM. Our recent
      experiments in animal models demonstrate that inhibition of c-Jun N terminal
      kinase (JNK) inhibits multiple pathological processes and causes regression of
      established AAA. Thus, emerging evidence indicates that pharmacological
      intervention targeting pro-inflammatory signaling and abnormal ECM metabolism is
      a promising strategy for treatment of AAA.

PMID- 17522834
TI  - [DNA methylation on urinalysis and as a prognostic marker in urothelial cancer of
      the bladder].
AB  - INTRODUCTION AND OBJECTIVES: Detection of promoter hypermethylation has been
      proposed as a promising tool for cancer diagnosis and as a prognostic marker in
      various cancers. We studied the versatility of DNA methylation for noninvasive
      diagnosis and as a prognostic marker for non-muscle-invasive bladder carcinoma.
      METHODS: Tumor specimens were microdissected and DNA was extracted from 105
      paraffin-embedded paraffin specimens from patients undergoing transurethral
      resection for non-muscle-invasive bladder carcinoma. Urine specimens were
      collected from patients undergoing cystectomy for bladder cancer and from healthy
      volunteers. Methylation status was assessed with the real-time quantitative
      methylation-sensitive PCR (MethyLight). We checked a panel of 20 cancer
      associated genes (p14ARF, p16 CDKN2A, STAT-1, SOCS-1, DR-3, DR-6, PIG-7, BCL-2, H
      TERT, BAX, EDNRB, DAPK, RASSF-1A, FADD, TMS-1, E-CADHERIN, ICAM-1, TIMP-3, MLH-1,
      COX-2) for DNA methylation. RESULTS: Follow-up data were available in 95 of 105
      patients (91.4%). A tumor recurrence was observed in 26 patients (27.3%). We
      could identify six genes (SOCS-1, STAT-1, BCL-2, DAPK, TIMP-3, E-cadherin), where
      methylation was associated with tumor recurrence. In Kaplan-Meier analysis, TIMP
      3 showed a significant association with recurrence-free survival. Methylation of
      TIMP-3 predicted prolonged disease-free interval. Regarding urinalysis we could
      identify a pattern of methylation markers including DAPK, BCL-2, and H-TERT that
      yielded a sensitivity of 81.1% with a specificity of 100% in a cancer-free
      control population CONCLUSIONS: We present data on the clinical usefulness of
      methylation analysis in bladder carcinoma. Our data confirm that methylation
      analysis is a promising tool for bladder cancer diagnosis and prognosis.

PMID- 17522835
TI  - Leveraging the rice genome sequence for monocot comparative and translational
      genomics.
AB  - Common genome anchor points across many taxa greatly facilitate translational and
      comparative genomics and will improve our understanding of the Tree of Life. To
      add to the repertoire of genomic tools applicable to the study of
      monocotyledonous plants in general, we aligned Allium and Musa ESTs to Oryza BAC
      sequences and identified candidate Allium-Oryza and Musa-Oryza conserved intron
      scanning primers (CISPs). A random sampling of 96 CISP primer pairs, representing
      loci from 11 of the 12 chromosomes in rice, were tested on seven members of the
      order Poales and on representatives of the Arecales, Asparagales, and
      Zingiberales monocot orders. The single-copy amplification success rates of
      Allium (31.3%), Cynodon (31.4%), Hordeum (30.2%), Musa (37.5%), Oryza (61.5%),
      Pennisetum (33.3%), Sorghum (47.9%), Zea (33.3%), Triticum (30.2%), and
      representatives of the palm family (32.3%) suggest that subsets of these primers
      will provide DNA markers suitable for comparative and translational genomics in
      orphan crops, as well as for applications in conservation biology, ecology,
      invasion biology, population biology, systematic biology, and related fields.

PMID- 17522838
TI  - [Possibilities for process optimization in orthopedic surgery].
AB  - It is mandatory to include all professions involved in the operating room (OR) in
      any attempt to improve the process. Early and detailed planning, short
      interruptions to change OR patients and a variable end of the day combined with
      transparent decision hierarchies help to ensure that things run smoothly.
      Parallel processes are essential for accelerating the change of patients. The
      different duties and responsibilities have to be documented. This can be done
      either in the records of quality management or in a special OR statutes. The
      evaluation and analysis of process critical parameters, including surgery as well
      as anesthesiology, are essential for maintaining the continuous process of
      improvement.

PMID- 17522836
TI  - Single residue (K332A) substitution in Kir6.2 abolishes the stimulatory effect of
      long-chain acyl-CoA esters: indications for a long-chain acyl-CoA ester binding
      motif.
AB  - AIMS/HYPOTHESIS: The pancreatic beta cell ATP-sensitive potassium (K(ATP))
      channel, composed of the pore-forming alpha subunit Kir6.2, a member of the
      inward rectifier K+channel family, and the regulatory beta subunit sulfonylurea
      receptor 1 (SUR1), a member of the ATP-binding cassette superfamily, couples the
      metabolic state of the cell to electrical activity. Several endogenous compounds
      are known to modulate K(ATP) channel activity, including ATP, ADP,
      phosphatidylinositol diphosphates and long-chain acyl coenzyme A (LC-CoA) esters.
      LC-CoA esters have been shown to interact with Kir6.2, but the mechanism and
      binding site(s) have yet to be identified. MATERIALS AND METHODS: Using multiple
      sequence alignment of known acyl-CoA ester interacting proteins, we were able to
      identify four conserved amino acid residues that could potentially serve as an
      acyl-CoA ester-binding motif. The motif was also recognised in the C-terminal
      region of Kir6.2 (R311-332) but not in SUR1. RESULTS: Oocytes expressing
      Kir6.2DeltaC26 K332A repeatedly generated K(+)currents in inside-out membrane
      patches that were sensitive to ATP, but were only weakly activated by 1 mumol/l
      palmitoyl-CoA ester. Compared with the control channel (Kir6.2DeltaC26),
      Kir6.2DeltaC26 K332A displayed unaltered ATP sensitivity but significantly
      decreased sensitivity to palmitoyl-CoA esters. Coexpression of Kir6.2DeltaC26
      K332A and SUR1 revealed slightly increased activation by palmitoyl-CoA ester but
      significantly decreased activation by the acyl-CoA esters compared with the wild
      type K(ATP) channel and Kir6.2DeltaC26+SUR1. Computational modelling, using the
      crystal structure of KirBac1.1, suggested that K332 is located on the
      intracellular domain of Kir6.2 and is accessible to intracellular modulators such
      as LC-CoA esters. CONCLUSIONS/INTERPRETATION: These results verify that LC-CoA
      esters interact at the pore-forming subunit Kir6.2, and on the basis of these
      data we propose an acyl-CoA ester binding motif located in the C-terminal region.

PMID- 17522839
TI  - [Foreign blood saving measures in orthopedic surgery].
AB  - Major transfusion-free orthopaedic surgery can be performed successfully. This
      requires advanced planning, good routines and close collaborative team efforts.
      Since most blood saving techniques reduce blood usage by just 1-2 units, a series
      of integrated preoperative, intraoperative and postoperative blood saving
      approaches is required. These include preoperative autologous donation,
      erythropoietic support, acute normovolemic hemodilution, intraoperative
      autotransfusion, individualized assessment of anemia tolerance, meticulous
      surgical techniques and the use of pharmacologic agents for limiting blood loss.
      For various reasons, we do not recommend the transfusion of wound drainage. This
      article describes the various methods for bloodless medical care.

PMID- 17522840
TI  - [Analysis of the effectiveness of an internal hospital bone bank].
AB  - BACKGROUND: The EU guidelines 2004/23/EG and 2006/17/EG and their national
      implementation redefine the framework for allogenic bone banking and
      transplantation. Against this background an established internal hospital bone
      bank was analysed concerning threshold of allogenic bone and cost effectiveness
      in comparison to alternative methods. METHOD: Over a 30-month period we
      registered all arrivals and outgoings of our bone bank and their destination. We
      further noted all declined donations. We analysed all costs incurred and
      calculated costs for alternative methods. RESULTS: By means of our bone bank we
      are currently able to meet our own demand for bone substitutes. The maintenance
      costs are below the prices of alternative methods. Some donations (8%) have to be
      discarded due to procedural errors. CONCLUSION: Maintaining an internal hospital
      bone bank utilizing fresh-frozen allogenic bone is an efficient and cost
      effective method of supplying bone substitutes even under the new EU guidelines
      if the existing process covers most conditions of the producer authorisation
      according to section sign 13 AMG. By harmonizing the organizational process it is
      possible to further improve its effectiveness.

PMID- 17522841
TI  - [Does mental training improve learning to walk with an above-knee prosthesis?].
AB  - BACKGROUND: Mental training is a method for optimizing movement patterns, which
      has become well established through its application in high performance sport and
      is also adopted in therapeutic contexts. The question arises as to whether the
      process of learning to walk following the fitting of a femoral prosthesis can be
      enhanced by means of mental training. METHODS: In the framework of a prospective
      randomized study, healthy subjects (36 students) were required to learn to walk
      with a femoral prosthesis: the control group (n=18) exclusively with the aid of
      practical training and the experimental group (n=18) with practical and mental
      training. Dependent variables were specified as the gait parameters of a computer
      supported and an observational gait analysis. RESULTS: In comparison to the
      control group, the experimental group made significantly faster learning progress
      in all parameters of the computer-supported and observational gait analysis.
      CONCLUSIONS: Mental training seems to be an effective gait training method
      following the fitting of a femoral prosthesis. Transferring this method to
      rehabilitation, particularly in young patients, would most certainly appear
      feasible.

PMID- 17522842
TI  - [Functional reconstruction of the radial articular surface after giant cell
      tumor].
AB  - Giant cell tumor is a benign locally aggressive tumor with a high tendency to
      recurrence, with a small rate of pulmonary metastases. In 90% of cases the tumor
      occurs in the long bones, especially near the epiphysis. A case of a 37-year-old
      female with a recurrent giant cell tumor of the distal radius including the
      radioulnar articular surface, successfully treated with a wide resection and
      reconstruction of the articular surface between the radius, scaphoid, lunatum,
      and ulna by an iliac crest graft, is reported.

PMID- 17522843
TI  - Semicontinuous intra-abdominal pressure measurement using an intragastric
      Compliance catheter.
AB  - OBJECTIVE: To compare intra-abdominal pressure (IAP) measurements obtained from
      an intragastric Compliance catheter with the pressure measured directly in the
      abdominal cavity. DESIGN AND SETTING: Prospective cohort study in an operating
      room of the Ghent University Hospital PATIENTS: Seven patients undergoing
      elective laparoscopic cholecystectomy. INTERVENTIONS: IAP was obtained from both
      an intragastric catheter and directly from the peritoneal cavity at 1-minute
      intervals in patients undergoing elective cholecystectomy and compared using
      Bland-Altman analysis. MEASUREMENTS AND RESULTS: In 156 paired measurements
      obtained from 7 patients the mean difference between IAPgastric and IAPref was
      0.12+/-0.70 mmHg (95% CI 0.01-0.23). CONCLUSIONS: IAP measured using an
      intragastric Compliance catheter reliably reflects the reference IAP in patients
      undergoing laparoscopic cholecystectomy.

PMID- 17522844
TI  - Neuromonitoring in the intensive care unit. I. Intracranial pressure and cerebral
      blood flow monitoring.
AB  - BACKGROUND: Monitoring the injured brain is an integral part of the management of
      severely brain injured patients in intensive care. Brain-specific monitoring
      techniques enable focused assessment of secondary insults to the brain and may
      help the intensivist in making appropriate interventions guided by the various
      monitoring techniques, thereby reducing secondary brain damage following acute
      brain injury. DISCUSSION: This review explores methods of monitoring the injured
      brain in an intensive care unit, including measurement of intracranial pressure
      and analysis of its waveform, and techniques of cerebral blood flow assessment,
      including transcranial Doppler ultrasonography, laser Doppler and thermal
      diffusion flowmetry. CONCLUSIONS: Various modalities are available to monitor the
      intracranial pressure and assess cerebral blood flow in the injured brain in
      intensive care unit. Knowledge of advantages and limitations of the different
      techniques can improve outcome of patients with acute brain injury.

PMID- 17522845
TI  - Influence of an acute increase in systemic vascular resistance on transpulmonary
      thermodilution-derived parameters in critically ill patients.
AB  - OBJECTIVE: The transpulmonary thermodilution technique enables measurement of
      cardiac index (CI), intrathoracic blood volume (ITBV), global end-diastolic
      volume (GEDV), and extravascular lung water (EVLW). In this study, we analyzed
      the robustness of this technique during an acute increase in systemic vascular
      resistance (SVR). DESIGN: Prospective, clinical study. SETTING: Surgical
      intensive care unit in a university hospital. PATIENTS AND METHODS: Twenty-four
      mechanically ventilated septic shock patients, who for clinical indications
      underwent extended hemodynamic monitoring by transpulmonary thermodilution and
      continuously received norepinephrine. INTERVENTIONS AND MAIN RESULTS: After
      baseline measurements, mean arterial pressure was increased briefly by increasing
      norepinephrine dosage and hemodynamic measurements were repeated before a control
      measurement was obtained. At each time point, 15 cc of 0.9% saline (< 8 degrees
      C) was administered by central venous injection in triplicate. Fluid status and
      respirator adjustments were kept constant. ANOVA with an all-pairwise comparison
      method was used for statistical analysis. Heart rate, central venous pressure,
      and EVLW remained constant throughout, while SVR significantly changed from 551
      +/- 106 to 746 +/- 91 dyn*s*cm(-5) and again to 566 +/- 138 dyn*s*cm(-5) (p <
      0.05). However, CI and central blood volumes showed a reversible significant
      increase, i.e., ITBV went from 816 +/- 203 to 867 +/- 195 ml/m(2) and then to 821
      +/- 205 ml/m(2) and GEDV from 703 +/- 178 to 747 +/- 175 ml/m(2) and finally to
      704 +/- 170 ml/m(2), respectively. In eight patients, 2-D echocardiography was
      applied and revealed a reversible increase in left-ventricular end-diastolic
      area. CONCLUSION: An acute increase in SVR by increasing norepinephrine dosage
      results in a reversible increase in central blood volumes (ITBV, GEDV) as
      measured by transpulmonary thermodilution and supported by echocardiography.

PMID- 17522846
TI  - Neuromonitoring in the intensive care unit. II. Cerebral oxygenation monitoring
      and microdialysis.
AB  - BACKGROUND: Monitoring the injured brain is an integral part of the management of
      severely brain injured patients in intensive care. There is increasing interest
      in methods to monitor global and regional cerebral oxygenation. There have been
      significant advances in analysing tissue oxygenation and local metabolites in the
      injured brain over the past decade. DISCUSSION: Cerebral oxygenation can be
      assessed on a global or regional basis by jugular venous oximetry and near infra
      red spectroscopy respectively. Techniques of brain tissue oxygenation monitoring
      and microdialysis are also covered in this review. CONCLUSIONS: Various
      modalities are available to monitor oxygenation and the local milieu in the
      injured brain in the intensive care unit. Use of these modalities helps to
      optimise brain oxygen delivery and metabolism in patients with acute brain
      injury.

PMID- 17522847
TI  - Chlorobenzoate inhibits growth and induces stress proteins in the PCB-degrading
      bacterium Burkholderia xenovorans LB400.
AB  - Aerobic bacteria, such as Burkholderia xenovorans LB400, are able to degrade a
      wide range of polychlorobiphenyls (PCBs). Generally, these bacteria are not able
      to transform chlorobenzoates (CBAs), which accumulate during PCB degradation. In
      this study, the effects of CBAs on the growth, the morphology and the proteome of
      Burkholderia xenovorans LB400 were analysed. 4-CBA and 2-CBA were observed to
      inhibit the growth of strain LB400 on glucose. Strain LB400 exposed to 4-CBA
      exhibited increased number and size of electron-dense granules in the cytoplasm,
      which could be polyphosphates. Two-dimensional (2-D) polyacrylamide gel
      electrophoresis was used to characterise the molecular response of strain LB400
      to 4-CBA. This compound induced the enzymes BenD and CatA of benzoate and
      catechol catabolic pathways. The induction of molecular chaperones DnaK and HtpG
      by 4-CBA indicated that the exposure to this compound constitutes a stressful
      condition for this bacterium. Additionally, the induction of some Krebs cycle
      enzymes was observed, probably as response to cellular energy requirements. This
      study contributes to the knowledge on the effects of CBA on the PCB-degrader
      Burkholderia xenovorans LB400.

PMID- 17522849
TI  - A critical comparison of analytical flow systems exploiting streamlined and
      pulsed flows.
AB  - Multipumping (MPFS) and multicommuted (MCFS) flow systems relying on pulsed and
      laminar flows were critically compared. The mixing conditions and dispersion
      associated with both systems were evaluated by simulating the sample with
      bromocresol green. The molybdenum blue method for phosphate determination in soil
      extracts was also implemented in both flow systems. Furthermore, laser-induced
      fluorescence (LIF) was applied to visualize the dispersing sample; rhodamine B
      was used as the fluorescent species. The pulsed flow enhanced the mixing of the
      solutions involved, thus reducing reagent consumption (48 and 96 microl for MPFS
      and MCFS), and improving sampling rate (67 and 144 h(-1) for MCFS and MPFS). For
      phosphate determination, results obtained with both systems were precise (r.s.d.
      < 0.5%; n = 10) and accurate. Analyses of the absorbance vs time/space LIF plots
      revealed that exploitation of pulsed flow led to a pronounced radial dispersion
      and to a limited axial dispersion, typical aspects of turbulent flows.

PMID- 17522850
TI  - Perception of finger forces within the hand after index finger fatiguing
      exercise.
AB  - The effect of fatigue on finger force perception within a hand during ipsilateral
      finger force matching was examined. Thirteen subjects were instructed to match a
      reference force of an instructed finger using the same or different finger within
      the hand before and after index finger fatigue. Absolute reference force targets
      for the index or little finger were identical during pre- and post-fatigue
      sessions. Fatigue was induced by a 60-s sustained maximal voluntary contraction
      (MVC) of the index finger. Index finger MVC decreased approximately 29%, while
      there was a non-significant (about 5%) decrease in the little finger MVC. The
      results showed that: (1) the absolute reference and matching forces of the
      instructed fingers were not significantly changed after fatigue, while the total
      forces (sum of instructed and uninstructed finger forces) were increased after
      fatigue. (2) The relative forces (with respect to corresponding pre- and post
      fatigue MVCs) of the index finger increased significantly in both reference and
      matching tasks, while the relative forces of the little finger remained unchanged
      after fatigue. (3) Matching errors remained unchanged after fatigue when the
      fatigued index finger produced the reference force, while the errors increased
      significantly when the fatigued index finger produced the matching force. (4)
      Enslaving (difference between total and instructed finger forces) increased
      significantly after fatigue, especially during force production by the fatigued
      index finger and when the little finger produced matching forces at higher force
      levels. (5) Enslaving significantly increased matching errors particularly after
      fatigue. Taken together, our results suggest that absolute finger forces within
      the hand are perceived within the CNS during ipsilateral finger force matching.
      Perception of absolute forces of the fatigued index finger is not altered after
      fatigue. The ability of the fatigued index finger to reproduce little finger
      forces is impaired to a certain degree, however. The impairment is likely to be
      attributable to altered afferent/efferent relationships of the fatigued index
      finger.

PMID- 17522851
TI  - Specific features of sensorimotor cerebral cortex activity modulation by dopamine
      releaser amantadine.
AB  - The modulatory effects of amantadine (1-adamantanamine) on the activity of
      sensorimotor cerebral cortex neurones during microiontophoretic application of
      agonists of glutamatergic and GABA-ergic (gamma-aminobutyric acid) transmission
      were studied. In non-anaesthetised cats, dopamine (DA) released by amantadine
      application in a small area of the neocortex increased baseline and evoked
      neuronal activity, providing stabilization and optimum course of both the
      neuronal and the conditioned responses of the animal. Amantadine eliminates a
      decrease in the level of neuronal baseline and evoked activity and marked
      increase in the latency of neuronal activation and conditioned movement mediated
      by D2 receptor antagonist sulpiride ((S)-5-aminosulfonyl-N-[(1-ethyl-2
      pyrrolidinyl) methyl]-2-methoamantadineybenzamide) or GABA. This is reflected by
      a proportionate decrease in the onset of neuronal impulse reaction and latency of
      conditioned movement. Combined NMDA (N-methyl-D: -aspartate) and amantadine
      application also caused a considerable increase in baseline and evoked activity,
      but produced a slightly weaker effect than that evoked by NMDA application alone.
      A decrease in the baseline and evoked neuronal activity after NMDA withdrawn
      lasted during next control session (up to 40 min). The ability of DA releaser
      amantadine to alleviate significant increase in the latency of neuronal responses
      and conditioned movement induced by sulpiride or GABA suggests that dopamine
      modulates the activity of GABA-ergic inhibitory fast spike interneurons in the
      cat sensorimotor cortex during conditioning.

PMID- 17522852
TI  - Reversible focal splenial lesions.
AB  - Reversible focal lesions in the splenium of the corpus callosum (SCC) have
      recently been reported. They are circumscribed and located in the median aspect
      of the SCC. On MRI, they are hyperintense on T2-W and iso-hypointense on T1-W
      sequences, with no contrast enhancement. On DWI, SCC lesions are hyperintense
      with low ADC values, reflecting restricted diffusion due to cytotoxic edema. The
      common element is the disappearance of imaging abnormalities with time, including
      normalization of DWI. Clinical improvement is often reported. The most
      established and frequent causes of reversible focal lesions of the SCC are viral
      encephalitis, antiepileptic drug toxicity/withdrawal and hypoglycemic
      encephalopathy. Many other causes have been reported, including traumatic axonal
      injury. The similar clinical and imaging features suggest a common mechanism
      induced by different pathological events leading to the same results. Edema and
      diffusion restriction in focal reversible lesions of the SCC have been attributed
      to excitotoxic mechanisms that can result from different mechanisms; no unifying
      relationship has been found to explain all the pathologies associated with SCC
      lesions. In our opinion, the similar imaging, clinical and prognostic aspects of
      these lesions depend on a high vulnerability of the SCC to excitotoxic edema and
      are less dependent on the underlying pathology. In this review, the relevant
      literature concerning reversible focal lesions in the SCC is analyzed and
      hypotheses about their pathogenesis are proposed.

PMID- 17522853
TI  - Intracranial extracerebral glioneuronal heterotopia with fetal laminar
      organization on MR imaging.
AB  - We present the brain MR imaging findings in a 13-month-old male infant with
      intracranial extracerebral brain tissue demonstrating the typical laminar
      organization pattern of fetal cerebral wall accompanied by unilateral
      anophthalmia and ethmoidal encephalocele supported by CT imaging.

PMID- 17522854
TI  - Domain interaction in cyanobacterial phytochromes as a prerequisite for spectral
      integrity.
AB  - Two phytochromes, CphA and CphB, from the cyanobacterium Calothrix PCC7601, with
      similar size (768 and 766 amino acids) and domain structure, were investigated
      for the essential length of their protein moiety required to maintain the
      spectral integrity. Both proteins fold into PAS-, GAF-, PHY-, and Histidine
      kinase (HK) domains. CphA binds a phycocyanobilin (PCB) chromophore at a
      "canonical" cysteine within the GAF domain, identically as in plant phytochromes.
      CphB binds biliverdin IXalpha at cysteine24, positioned in the N-terminal PAS
      domain. The C-terminally located HK and PHY domains, present in both proteins,
      were removed subsequently by introducing stop-codons at the corresponding DNA
      positions. The spectral properties of the resulting proteins were investigated.
      The full-length proteins absorb at (CphA) 663 and 707 nm (red-, far red-absorbing
      P (r) and P (fr) forms of phytochromes) and at (CphB) 704 and 750 nm. Removal of
      the HK domains had no effect on the absorbance maxima of the resulting PAS-GAF
      PHY constructs (CphA: 663/707 nm, CphB: 704/750 nm, P (r)/P (fr), respectively).
      Further deletion of the "PHY" domains caused a blue-shift of the P (r) and P (fr)
      absorption of CphA (lambda (max): 658/698 nm) and increased the amount of
      unproperly folded apoprotein, seen by a reduced capability to bind the
      chromophore in photoconvertible manner. In CphB, however, it practically impaired
      the formation of P (fr), i.e., showing a very low oscillator strength absorption
      band, whereas the P (r) form remains unchanged (702 nm). This finding clearly
      indicates a different interaction between domains in the "typical", PCB binding
      and in the biliverdin-binding phytochromes, and demonstrates a loss of oscillator
      strength for the latter, most probably due to a strong conformational distortion
      of the chromophore in the CphB P (fr) form.

PMID- 17522855
TI  - A simple genetic algorithm for the optimization of multidomain protein homology
      models driven by NMR residual dipolar coupling and small angle X-ray scattering
      data.
AB  - Most proteins comprise several domains and/or participate in functional
      complexes. Owing to ongoing structural genomic projects, it is likely that it
      will soon be possible to predict, with reasonable accuracy, the conserved regions
      of most structural domains. Under these circumstances, it will be important to
      have methods, based on simple-to-acquire experimental data, that allow to build
      and refine structures of multi-domain proteins or of protein complexes from
      homology models of the individual domains/proteins. It has been recently shown
      that small angle X-ray scattering (SAXS) and NMR residual dipolar coupling (RDC)
      data can be combined to determine the architecture of such objects when the X-ray
      structures of the domains are known and can be considered as rigid objects. We
      developed a simple genetic algorithm to achieve the same goal, but by using
      homology models of the domains considered as deformable objects. We applied it to
      two model systems, an S1KH bi-domain of the NusA protein and the gammaS
      crystallin protein. Despite its simplicity our algorithm is able to generate good
      solutions when driven by SAXS and RDC data.

PMID- 17522856
TI  - Availability and applications of ATP-binding cassette (ABC) transporter blockers.
AB  - ATP-binding cassette (ABC) transporters encompass membrane transport proteins
      that couple the energy derived from ATP hydrolysis to the translocation of
      solutes across biological membranes. The functions of these proteins include
      ancient and conserved mechanisms related to nutrition and pathogenesis in
      bacteria, spore formation in fungi, and signal transduction, protein secretion
      and antigen presentation in eukaryotes. Furthermore, one of the major causes of
      drug resistance and chemotherapeutic failure in both cancer and anti-infective
      therapies is the active movement of compounds across membranes carried out by ABC
      transporters. Thus, the clinical relevance of ABC transporters is enormous, and
      the membrane transporters related to chemoresistance are among the best-studied
      members of the ABC transporter superfamily. As ABC transporter blockers can be
      used in combination with current drugs to increase their efficacy, the (possible)
      impact of efflux pump inhibitors is of great clinical interest. The present
      review summarizes the progress made in recent years in the identification,
      design, availability, and applicability of ABC transporter blockers in
      experimental scenarios oriented towards improving the treatment of infectious
      diseases caused by microorganisms including parasites.

PMID- 17522857
TI  - Partial volume correction of standardized uptake values and the dual time point
      in FDG-PET imaging: should these be routinely employed in assessing patients with
      cancer?

PMID- 17522858
TI  - Prospective comparison of two gamma probes for intraoperative detection of 18F
      FDG: in vitro assessment and clinical evaluation in differentiated thyroid cancer
      patients with iodine-negative recurrence.
AB  - PURPOSE: This study was aimed at evaluating the spatial resolution and
      sensitivity of two hand-held gamma probes. Radioguided surgery was tested in
      seven patients with iodine-negative differentiated thyroid cancer (DTC)
      recurrence using (18)F-FDG PET. METHODS: Two gamma probes were evaluated:
      Clerad's GammaSup with a collimated CsI(Tl) scintillator and Novelec's Modelo2
      with a BGO scintillator. Five measurement tests were performed following the NEMA
      guidelines (NU3-2004). Radioguided surgery was performed in patients with
      recurrent DTC and abnormal (18)F-FDG uptake on preoperative (18)F-FDG PET images.
      Patients were injected with rTSH 2 days before surgery. A mean activity of 211
      MBq of (18)F-FDG was injected 60 min before surgery. In vivo and ex vivo counts
      were recorded for suspected tumours and normal tissue. RESULTS: Spatial
      resolution was higher with the CsI(Tl) than with the BGO detector: 20.2-40.6 mm
      vs 20.6-55.3 mm from 0 to 20 mm depth. Sensitivity in air and water and through
      side shielding was higher for BGO but the signal-to-noise ratio was 88 and 22
      with the BGO compared to 131 and 76 with the CsI(Tl) at 10 and 30 mm depth.
      Median in vivo SNR (tumour/non-tumour ratio) was 1.8 with both the BGO and the
      CsI(Tl) detector, while ex vivo ratios of 2.3 and 2.1, respectively, were
      obtained. Radioguided surgery allowed detection of all of the tumours identified
      by (18)F-FDG PET images. CONCLUSION: This study demonstrated the feasibility of
      high-energy photon detection with a conventional scintillator equipped with a
      collimator. The CsI(TI) probe detected more true events from background than did
      the BGO detector during surgery.

PMID- 17522859
TI  - Specific CD8(+ )T cell responses to HLA-A2 restricted MAGE-A3 p271-279 peptide in
      hepatocellular carcinoma patients without vaccination.
AB  - The MAGE-A3 protein, one of the promising tumor antigens for immunotherapy, is
      highly expressed in human hepatocellular carcinoma (HCC). In this study, we
      estimated the specific CD8(+) T cell immune response to MAGE-A3 p271-279 peptide
      (M3(271)) in the peripheral blood of HCC patients without antigen vaccination in
      order to evaluate its immunotherapeutic potential in these patients. After
      expansion in vitro, the functional IFN-gamma producing M3(271) specific CD8(+) T
      cells were detected in 30.8% (8/26) of HLA-A2(+)MAGE-A3(+) HCC patients. The
      effector CD8(+ )T cells could release cytotoxic molecules of granzyme B and
      perforin after restimulation with natural HLA-A2(+)MAGE-A3(+) HCC cell lines in
      the samples tested. The functional supertype of HLA-A2 in the presentation of HLA
      A*0201 restricted M3(271) peptide has been identified in the Chinese HCC patients
      of Han ethnicity, that widely expanded the applicability of this tumor peptide
      vaccine in Chinese HCC patients. Thus, the functionally detectable pre-existence
      of M3(271)-specific CD8(+) T cells in HCC patients makes M3(271) a potential
      target for immunotherapy in these patients. The responsive CD8(+ )T cells to both
      NY-ESO-1 and MAGE-A3 antigens provide a rationale for the application of a
      bivalent vaccine in HCC patients with tumors expressing both antigens.

PMID- 17522860
TI  - Spontaneous and vaccine induced AFP-specific T cell phenotypes in subjects with
      AFP-positive hepatocellular cancer.
AB  - We are investigating the use of Alpha Fetoprotein (AFP) as a tumor rejection
      antigen for hepatocellular carcinoma (HCC). We recently completed vaccination of
      10 AFP+/HLA-A2.1+ HCC subjects with AFP peptide-pulsed autologous dendritic cells
      (DC). There were increased frequencies of circulating AFP-specific T cells and of
      IFNgamma-producing AFP-specific T cells after vaccination. In order to better
      understand the lack of association between immune response and clinical response,
      we have examined additional aspects of the AFP immune response in patients. Here,
      we have characterized the cell surface phenotype of circulating AFP tetramer
      positive CD8 T cells and assessed AFP-specific CD4 function. Before vaccination,
      HCC subjects had increased frequencies of circulating AFP-specific CD8 T cells
      with a range of naive, effector, central and effector memory phenotypes. Several
      patients had up-regulated activation markers. A subset of patients was assessed
      for phenotypic changes pre- and post-vaccination, and evidence for complete
      differentiation to effector or memory phenotype was lacking. CD8 phenotypic and
      cytokine responses did not correlate with level of patient serum AFP antigen
      (between 74 and 463,040 ng/ml). Assessment of CD4+ T cell responses by ELISPOT
      and multi-cytokine assay did not identify any spontaneous CD4 T cell responses to
      this secreted protein. These data indicate that there is an expanded pool of
      partially differentiated AFP-specific CD8 T cells in many of these HCC subjects,
      but that these cells are largely non-functional, and that a detectable CD4 T cell
      response to this secreted oncofetal antigen is lacking.

PMID- 17522861
TI  - Preferential migration of regulatory T cells mediated by glioma-secreted
      chemokines can be blocked with chemotherapy.
AB  - Despite the immunogenicity of glioblastoma multiforme (GBM), immune-mediated
      eradication of these tumors remains deficient. Regulatory T cells (Tregs) in the
      blood and within the tumor microenvironment of GBM patients are known to
      contribute to their dismal immune responses. Here, we determined which chemokine
      secreted by gliomas can preferentially induce Treg recruitment and migration. In
      the malignant human glioma cell lines D-54, U-87, U-251, and LN-229, the
      chemokines CCL22 and CCL2 were detected by intracellular cytokine analysis.
      Furthermore, tumor cells from eight patients with GBM had a similar chemokine
      expression profile. However, only CCL2 was detected by enzyme-linked
      immunosorbent assay, indicating that CCL2 may be the principal chemokine for Treg
      migration in GBM patients. Interestingly, the Tregs from GBM patients had
      significantly higher expression levels of the CCL2 receptor CCR4 than did Tregs
      from healthy controls. Glioma supernatants and the recombinant human chemokines
      CCL2 and CCL22 induced Treg migration and were blocked by antibodies to the
      chemokine receptors. Production of CCL2 by glioma cells could also be mitigated
      by the chemotherapeutic agents temozolomide and carmustine [3-bis (2-chloroethyl)
      1-nitrosourea]. Our results indicate that gliomas augment immunosuppression by
      selective chemokine-mediated recruitment of Tregs into the tumor microenvironment
      and that modulating this interaction with chemotherapy could facilitate the
      development of novel immunotherapeutics to malignant gliomas.

PMID- 17522862
TI  - Rituximab in the management of post-transplantation lymphoproliferative disorder
      after solid organ transplantation: proceed with caution.
AB  - The introduction of single-agent rituximab has markedly changed the approach to
      therapy of patients with post-transplantation lymphoproliferative disorder
      (PTLD), but response to treatment varies substantially between patients. In the
      current report, we analyze long-term efficacy of single-agent rituximab in 60
      patients and present factors predictive of progression-free and overall survival.
      Twelve months after completing first-line treatment, 34 of 60 patients (57%) had
      progressive disease, resulting in a median progression-free survival of 6.0
      months at a median follow-up of 16.3 months. Using multivariate Cox regression
      analysis, the following factors were identified as significantly predictive of
      overall survival: age at diagnosis, performance status, lactate dehydrogenase
      (LDH), and time from transplantation to PTLD. Stage of disease and Epstein-Barr
      virus association of PTLD did not influence overall survival. LDH and time from
      transplantation to PTLD were also predictive of progression-free survival. The
      international prognostic index was shown to be of limited predictive value in
      these patients, but a PTLD-specific prognostic index separated low-, intermediate
      , and high-risk patients with high significance: 2-year overall survival rates
      after first-line treatment with single-agent rituximab were 88, 50, and 0%,
      respectively. Thus, prognostic indices can be useful tools for prediction of
      treatment outcome and for the development of risk-adapted treatment strategies in
      patients with PTLD and may also provide the basis for interstudy comparisons.

PMID- 17522863
TI  - Capecitabine in combination with Oxaliplatin (XELOX) as a first-line therapy for
      advanced gastric cancer.
AB  - PURPOSE: We evaluated efficacy and safety of XELOX in previously untreated
      patients with AGC. PATIENTS AND METHODS: Patients received intravenous
      oxaliplatin 130 mg/m(2) over 2 h on day 1 plus oral capecitabine 1,000 mg/m(2)
      twice daily on days 1-14, every 3 weeks (XELOX). Treatment was continued until
      disease progression, intolerable toxicities or eight cycles reached. All tumour
      evaluations were reviewed and confirmed centrally. Design was according to
      Ensign's three-stage method. RESULTS: Fifty-four patients (37 men) were enrolled;
      median age 57 years (range 29-70). In total, 311 cycles of XELOX were delivered.
      Overall response rate was 63% (95% CI, 50-76%), with 3 complete and 31 partial
      responses. At 13 months' median follow-up, median progression-free and overall
      survival were 5.8 (95% CI, 4.4-7.2) and 11.9 months (95% CI, 8.8-15.1),
      respectively. The most common haematological adverse event was anaemia (70% of
      patients). Grade 3-4 neutropenia was observed in four patients, with neutropenic
      fever in only one patient. Most common non-haematological toxicities were
      neuropathy (70%), vomiting (50%), diarrhoea (33%), and hand-foot syndrome (HFS)
      (39%). Grade 3-4 toxicities were rare. Treatment was delayed or the dose reduced
      in 30 and 15% of cycles, respectively. There was one treatment-related death
      associated with grade 4 neutropenic sepsis. CONCLUSION: XELOX was active and well
      tolerated as a first-line therapy for AGC.

PMID- 17522864
TI  - Preclinical studies of the proteasome inhibitor bortezomib in malignant pleural
      mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm that is
      resistant to chemotherapy. Bortezomib is an FDA-approved proteasome inhibitor
      that is currently under clinical investigation in multiple neoplasms but has not
      been studied extensively in MPM. In this report, we determine the biological and
      molecular response of cultured MPM cells to bortezomib alone and in combination
      with cisplatin or pemetrexed. We used four MPM cell lines (MS589, H28, H2052,
      JMN), a normal mesothelial cell line (HM3), and a lung cancer cell line (H23) in
      survival studies utilizing bortezomib, cisplatin, and pemetrexed alone and in
      combination by administering concurrently or by varying the order of
      administration. We determined the effect of bortezomib on the cell cycle,
      apoptosis, and on the expression of cell cycle proteins p21/WAF1 and p27/KIP1 and
      on apoptosis-related proteins IAP-1, IAP-2, survivin, and XIAP. Bortezomib was
      highly cytotoxic to MPM cells and induced both G(2)/M and G(1)/S cell cycle
      arrest. Apoptosis increased in a concentration- and time-dependent manner in 3 of
      4 MPM cell lines. Bortezomib stabilized or increased protein levels of p21/WAF1
      and IAP-1 and to a lesser degree p27/KIP1, IAP-2, XIAP, and survivin. In
      combination studies with cisplatin, bortezomib was generally synergistic at high
      concentrations and antagonistic at low concentrations. Bortezomib increased the
      cytotoxicity of cisplatin and pemetrexed in a concentration-dependent manner when
      administered prior to either. Bortezomib may improve outcome in MPM patients
      alone or in combination with standard chemotherapy but the order of
      administration is likely to be important. This study justifies further evaluation
      of bortezomib in MPM.

PMID- 17522865
TI  - The intravertebral vacuum phenomen as specific sign of osteonecrosis in vertebral
      compression fractures: results from a radiological and histological study.
AB  - This study investigated the prevalence of the intravertebral vacuum phenomenon
      (IVP) and osteonecroses in vertebral compression fractures (VCFs). We therefore
      performed an histological analysis of biopsies obtained from VCFs prior to
      balloon kyphoplasty. Computed tomography (CT) scans were reviewed regarding the
      presence of an IVP (i.e. cleft sign, Kummell disease). We reviewed the data of
      266 consecutive patients treated by balloon kyphoplasty in 501 procedures from
      2002 to 2004. From 180 patients (68%) we obtained adequate bone tissue for
      histological evaluation. Biopsy specimens were analysed regarding the presence of
      osteoporosis, infection, malignancy and osteonecrosis. CT scans of all 180
      patients were reviewed for presence of an IVP. Histological examination revealed
      135 (75%) osteoporoses, 20 (11%) neoplasms, 12 (7%) trauma cases and 13 (7%)
      osteonecroses. An IVP was present in 12 (7%) patients. There was a significant
      association of osteonecrosis and IVP (P < 0.0001). Eleven of 12 patients with a
      vacuum phenomenon showed an osteonecrosis on histology, whereas 11 of 13 patients
      with osteonecrosis showed an IVP on CT. The IVP is a specific sign of
      osteonecrosis in vertebral compression fractures (sensitivity 85%, specificity
      99%, positive predictive value 91%). Our findings strongly support the thesis
      that an IVP indicates local bone ischemia associated with a non-healing vertebral
      collapse and pseudarthrosis.

PMID- 17522866
TI  - MR colonography vs. optical colonoscopy: comparison of patients' acceptance in a
      screening population.
AB  - The aim of this study was to compare optical colonoscopy to fecal-tagging-based
      MR colonography in a screening population in terms of comfort and acceptance
      ratings as well as for future preferences as colorectal cancer screening
      examinations. Two hundred eighty-four asymptomatic patients (mean age 59 years)
      underwent MRC and OC within 4 weeks. While MRC was based on a fecal tagging
      technique, OC was performed after bowel cleansing. For OC, sedatives and
      analgesics were used. Patients evaluated both modalities and certain aspects of
      the examination according to a 10-point-scale with higher scores denoting a worse
      experience. Furthermore, preferences for future examinations were evaluated. No
      significant difference was noted for the overall acceptance of OC (mean value
      3.0) and MRC (mean value 3.4). For MRC, the placement of the rectal tube was
      rated as the most unpleasant part, whereas bowel purgation was regarded most
      inconvenient for OC. Patients aged 55 years and older perceived most aspects less
      unpleasant than younger patients. Of the patients, 46% preferred MRC for future
      screening examinations (OC: 44%). OC and MRC have comparable general acceptance
      levels in a screening population. Especially for patients declining endoscopy as
      a screening method MRC may evolve as an attractive alternative.

PMID- 17522867
TI  - [Refractory intermediate uveitis in the presence of unexplained joint disease.
      Diagnosis: Tropheryma whipplei (Morbus Whipple)].

PMID- 17522868
TI  - [Secondary open angle glaucoma with idiopathic episcleral venous pressure (Radius
      Maumenee syndrome). Sinus-otomy as operative procedure of choice].

PMID- 17522869
TI  - Slide thyrocricotracheoplasty: a novel surgical technique for congenital
      laryngeal atresia.
AB  - The aim of this study was to introduce a new surgical technique for the
      correction of congenital laryngeal atresia. A female baby had laryngeal atresia
      at birth and received emergency tracheostomy at another hospital. The baby
      visited our hospital at 7 months of age for corrective surgery of airway
      obstruction. We used a new surgical technique for reconstruction of her airway,
      the slide thyrocricotracheoplasty, which was a modification of slide
      tracheoplasty and anterior cricoid split. The extubation was successful at the
      postoperative fifth day, and the baby was discharged on the 33rd day after
      operation. The serial follow-up bronchoscopy on the fourth and 18th postoperative
      months revealed good healing and normal growth of tissue at operation site
      without stenosis and granulation. Slide thyrocricotracheoplasty produced a
      desirable result and offered the same advantages as slide tracheoplasty. The
      authors believe that this technique offers an efficient surgical procedure for
      the single-staged correction of congenital laryngeal atresia.

PMID- 17522870
TI  - [Cytokines].
AB  - Cytokine driven inflammation is a common feature in autoimmune diseases.
      Cytokines are needed under physiological conditions within the innate and
      adaptive immune systems to control infectious diseases and neoplastic disorders
      by regulation of the cell cycle and apoptosis. Cytokines can also be found in
      persistently increased concentrations in inflamed tissues within autoimmune
      diseases. Therefore, the modulation of cytokines seems to be a worthwhile
      therapeutic approach. With TNFalpha and Il-1, two key cytokines in rheumatoid
      arthritis have been identified. Their inhibition leads to a convincing clinical
      benefit. In the near future, inhibition of additional cytokines, such as Il-6 or
      Il-15, will likely open new beneficial strategies.

PMID- 17522871
TI  - [Diagnosis, prophylaxis and therapy of osteoporosis in juvenile idiopathic
      arthritis: consensus statement of the German Association for Pediatric
      Rheumatology].
AB  - In all subgroups of juvenile idiopathic arthritis (JIA), a pathologic loss of
      bone or the lack of increase in bone mass has been described in a high percentage
      of cases, even with new therapeutic approaches. The decrease in bone mass is
      correlated with the duration of active disease and the number of affected joints
      (cytokines, inactivity). In several studies, muscle mass was the strongest
      predictor of bone mass. A standardized diagnostic approach to the musculoskeletal
      system including measures of prophylaxis and therapy therefore seems to be
      mandatory for all children with JIA who do not achieve rapid remission. In this
      review, the diagnostic and therapeutic options are described and summarized in an
      algorithm.

PMID- 17522872
TI  - [Changes for the field of rheumatology in the G-DRG-System 2007].
AB  - After extensive revision the partners of the self
      administration"Selbstverwaltung" reached an amicable agreement on the new version
      2007 of the G-DRG system. Like in the years before, version 2007 brings about
      large-scale changes for its users. A better representation of inpatient services
      in Germany combined with an improved economic homogeneity and appropriateness can
      be assumed. This is based on various factors, e. g. considerably increased data
      quality and the optimization of technical influences on the system. Due to the
      rising level of complexity it is hardly possible to maintain a clinically
      homogeneous classification on the basis of G-DRGs. There is need [This calls] for
      a new approach in strategic matters. Various initiatives succeeded in a
      continuous improvement how the services provided by specialised rheumatologic
      clinics and departments are represented in the G-DRG system. Meanwhile, even
      under the pressure caused by the period of convergence, quality standards were
      focused on as well. The systematic changes of version 2007 as well as
      modifications concerning co-payments, coding and accounting rules relevant for
      rheumatologic clinics are presented and the consequences for users are discussed.

PMID- 17522873
TI  - Implant-related infection model in rat spine.
AB  - OBJECTIVE: The rate of postoperative infections is approximately 1% in spine
      surgery. However, when metal implants are used, postoperative infection rates
      significantly increase and were reported between 2.1 and 8.5%. This study aim to
      set up an infection model in the rat spine with a metal implant. MATERIALS AND
      METHODS: Forty white male Sprague Dawley rats were randomly divided in four
      groups. In all rats, under operation microscope, a 3 mm titanium microscrew was
      implanted in the thoracolumbar area (T10-L1) after laminar decortication. In
      Group I (control group), sterile isotonic solution and in other three groups,
      different concentrations of Staphylococcus aureus [Group II: (10(2)), Group III:
      (10(3)), Group IV: (10(6))] were squirted on the decorticated lamina site. All
      animals were sacrificed after 2 weeks, and then blood cultures and cultures from
      fascia, muscle and bone were obtained. Bacterial number in each tissue was
      measured as colony-forming unit per gram tissue. Titanium microscrews were placed
      in 0.5 ml tryptic soy broth and vortexed than plated on trypticase soy agar to
      determine bacterial growth. Two animals from each group were subjected to
      histological examination. RESULTS: Blood cultures obtained by intra-atrial
      puncture after 2 weeks were negative in all groups indicating no systemical
      infection developed. Bacterial cultures were negative in all specimens of Group I
      (control group). A significant osseous infection was confirmed in Groups II, III
      and IV. Comparison of bacterial counts in bone cultures showed no significant
      difference between Group III (10(3) CFU/10 microl) and Group IV (10(6) CFU/10
      microl) (P > 0.05), while both groups had significantly higher counts than Group
      II (10(2) CFU/10 microl) (P > 0.05). Microscopic findings of supurrative
      inflammation were present only in Group IV (10(6) CFU/10 microl). CONCLUSIONS:
      This study shows that inoculation of S. aureus in 10(6) CFU/10 microl
      concentration at the decorticated lamina after implantation of a titanium screw
      in rat spine is a reproducible model for spinal infection and can be used for the
      animal model of prophylaxis and treatment and of postoperative infection.

PMID- 17522874
TI  - Relationship of body mass index to early complications in knee replacement
      surgery.
AB  - BACKGROUND: The purpose of this study was to evaluate the relationship between
      body mass index and early complications following knee replacement. METHODS: Five
      hundred and twenty-seven patients who underwent primary knee replacement were
      recruited. All these patients were subjected to a pre-operative assessment and
      follow-up at 6 weeks and 1 year following surgery. Any complication occurring
      during this period was recorded. Complications were grouped into systemic and
      local, minor and major. RESULTS: 12.1% (N = 64) patients had an early
      complication following knee replacement surgery; 9.2% (N = 48) patients had a
      major complication. Overall BMI did not seem to influence significantly the rate
      of complication with a P-value of 0.338. A stronger correlation was found between
      the surgeon and presence of complication with a P-value of 0.004. CONCLUSIONS:
      BMI has a weak correlation to early complications following joint replacement
      surgery. The operating surgeon seems to have a stronger correlation to early
      complications as compared with BMI.

PMID- 17522875
TI  - Changes of D-dimer after total hip arthroplasty in patients with and without
      intraoperative heparin.
AB  - INTRODUCTION: Marked activation of thrombosis is common in patients undergoing
      total hip arthroplasty, especially during reaming of the femur and after
      insertion of the femoral prosthesis. This suggests that management designed to
      minimize deep vein thrombosis and fatal pulmonary embolism after total hip
      arthroplasty should be focused on the period during insertion of the femoral
      component. In some previous studies, a low dose of heparin administered
      intraoperatively was shown to suppress the formation of fibrin. OBJECTIVE: The
      present study was performed to evaluate the influence of intraoperative heparin
      administration on the D-dimer level and on the prevention of pulmonary embolism
      after total hip arthroplasty. MATERIAL/METHODS: A total of 22 and 26 consecutive
      patients respectively underwent total hip arthroplasty with and without
      intraoperative administration of unfractionated heparin. Postoperatively, all
      patients wore knee-high elastic stockings and were fitted with calf-to-thigh
      intermittent pneumatic compression devices. Active ankle flexion and extension
      exercises were commenced as soon as motor function recovered. None of the 48
      patients received prophylactic anticoagulants postoperatively. RESULTS: There was
      a significant difference of the mean D-dimer level on the 1st day between the
      patients with and without intraoperative administration of heparin (8.9 +/- 6.6
      vs. 15.7 +/- 12.7, P < 0.05). Although there were no patients with symptomatic
      deep venous thrombosis and pulmonary embolism, asymptomatic pulmonary embolism
      was detected by pulmonary perfusion scintigraphy in three patients who did not
      receive intraoperative heparin. The operative blood loss and postoperative
      drainage were similar in both groups and no bleeding complications were observed.
      In conclusion, we recommend a safe and inexpensive regimen comprising 1,000 U of
      intravenous unfractionated heparin intraoperatively, postoperative pneumatic
      compression, and early active mobilization for prevention of thoromboembolic
      complications after total hip arthroplasty.

PMID- 17522876
TI  - Anatomical reconstruction for Reverse Hill-Sachs lesions after posterior locked
      shoulder dislocation fracture: a case series of six patients.
AB  - INTRODUCTION: Posterior locked shoulder dislocation fracture is a rare injury.
      Impression fractures of the humeral articular surface are common with this
      injury. Different methods exist to restore impression fractures. We present a
      case series and the results of six patients that had an anatomical repair with
      spongiotic autograft/allograft for humeral head impression fractures after locked
      posterior shoulder dislocation. MATERIAL AND METHODS: Six patients with an
      average age of 52.5 years at time of surgery were included. All patients had an
      anteromedial impression fracture, one patient had an additional two part
      fracture. The injury was caused by epileptic seizures in five and by direct
      trauma in one patient. The diagnosis was made on the day of the injury for two
      patients (33%). For the other patients the time span between the injury and the
      diagnosis ranged between 5 and 180 days. The impressed cartilage of the defect
      was first elevated in one piece, the defect filled with the graft and the
      cartilage fixed on top of the graft by Mitek ancres introduced under the affected
      area. One patient had an additional two-part fracture that was fixed separately.
      RESULTS: At a mean time follow-up of 62.7 (18-95) months the result was found to
      be excellent for two patients and good for four patients with a mean Constant
      Score of 88.2 points (range 83-98). One patient had a redislocation after three
      months that was fixed by the same method. At the last follow-up no redislocation
      or graft collapse was seen. CONCLUSION: The proposed method of anatomical head
      reconstruction by spongiotic auto/allograft proved to be a valid and good method
      to restore shoulder function and stability.

PMID- 17522877
TI  - Combined ulnar and carpal tunnel syndrome caused by pigmented villo-nodular
      tenosynovitis: a rare case.
AB  - Pigmented villo-nodular synovitis/tenosynovitis (PVNS) is a rare cause of
      combined ulnar and median nerve compression neuropathy at the wrist. In our case,
      a 53-year-old house-wife had sensorial and motor complaints at her left hand. In
      clinical examination, painless soft tissue mass was palpated at her wrist and
      both the tenar and hypotenar muscles were atrophic. Electromyography showed
      prolonged distal latencies for median and ulnar nerve. A space-occupying soft
      tissue lesion was revealed in magnetic resonance imaging. Carpal tunnel and Guyon
      canal were released and lesion was excised. PVNS was confirmed by
      histopathological examination. If compression neuropathy of medial and ulnar
      nerves together is caused by a space-occupying lesion, PVNS should be considered
      in etiology.

PMID- 17522878
TI  - A rare cause of thoracic outlet syndrome.
AB  - First rib pathology can narrow the thoracic outlet thus producing compression of
      the brachial plexus and subclavian vessels. There have been only three case
      reports of neurogenic thoracic outlet syndrome (TOS) caused by a nonunion of the
      first rib and there have been no reports of a first rib malunion causing TOS. A
      rare case of TOS caused by a malunion of the first rib is presented.

PMID- 17522879
TI  - Clear cell chondrosarcoma of bone: long time follow-up of 18 cases.
AB  - INTRODUCTION: Clear cell chondrosarcoma is a variant of conventional
      chondrosarcoma behaving as low grade malignant bone tumor. We reviewed our cases
      of clear cell chondrosarcoma with the aim to assess the best diagnostic and
      curative approach to this rare tumor. MATERIALS AND METHODS: We report 18 cases
      of clear cell chondrosarcoma treated at the authors' institution. Pertinent
      clinical information, pre and postoperative serum alkaline phosphatase (SAP)
      level were obtained from the patients charts. Available imaging studies including
      plain roentgenograms, computed tomography (CT) images (in 6 patients) and
      magnetic resonance imaging (MRI) images (in 2 patients). RESULTS: Eight cases
      were firstly treated in other institutions, seven with one or more curettage,
      while one, presented with pathologic fracture, was treated with repeated
      osteosynthesis. Of the seven patients treated with curettage, five were referred
      with local recurrence, the mean time between surgical treatment and local
      recurrence was 52.2 months (from 12 to 132). The other two patients were curetted
      out 4 and 1 month before, respectively, and were then referred to us to decide
      about further treatment after incidental diagnosis. Of these cases, three (37.5%)
      recurred again after our treatment and two of them presented with late bone
      metastases. Eight patients were originally treated with wide (six) or marginal
      (two) surgical margins by us. Among them only one proximal humerus (wide margins)
      had local recurrence 26 months from the first operation. Two patients underwent
      curettage in our institution, and one of them had a local recurrence. Pre
      operative SAP level were obtained in 17 patients. Among them, 11 patients had
      high pre-operative SAP level (64.7%) and 6 cases were normal. Post-operative SAP
      levels were obtained in nine patients. After removal of the tumors; SAP levels
      decreased to normality in seven of the nine patients with high pre-operative SAP.
      In the other two patients, although the SAP levels were normal, post-operative
      SAP levels were decreased. CONCLUSION: Serum alkaline phosphatase can be used as
      a good tumor marker in diagnosis and follow-up. Due to the occurrence of local
      recurrences and distant metastasis after curettage, we suggest surgical treatment
      with "en bloc" resection from the first presentation.

PMID- 17522880
TI  - Preoperative templating of femoral components on plain X-rays. Rotational
      evaluation with synthetic X-rays on ORTHODOC.
AB  - INTRODUCTION: Preoperative femoral templating for total hip arthroplasty (THA)
      has been performed by antero-posterior radiographs of both hips which should be
      taken with the femur rotated internally to reduce the effect of femoral
      anteversion. However, there is no criterion to evaluate the optimal rotated
      radiograph. Here, we quantitatively investigated 50 femora whether the thickness
      of the lesser trochanter (TLT) was useful when evaluating the femoral rotation,
      and assessed the effect of prosthetic templating on the inappropriate rotated
      radiographs. MATERIALS AND METHODS: We assessed 50 femora of 46 consecutive
      osteoarthritic patients using "synthetic X-ray" based on computer tomography (CT)
      images, which can be displayed as virtual plain radiographs with any
      magnification and any projected direction such as plain radiographs. We made four
      femoral radiograph groups of different rotation prepared (neutral, 15 degrees, 30
      degrees, and 45 degrees external rotation), and measured the TLT. We also
      templated femoral stem on the different rotated synthetic X-ray of each patient,
      and investigated the effect of inappropriate rotated radiograph by the
      measurement of the position and the size of the stem. RESULTS: Seventy-four
      percent of the neutral rotational group had less than 5 mm of the TLT. While 30
      degrees and 45 degrees external rotation group had few cases with less than 5 mm
      of the TLT. Compared to the neutral group, smaller stem size was selected in more
      than 80% cases of 30 degrees and 45 degrees external rotational group, and the
      stem position in these two groups was more than 5 mm proximally. CONCLUSION: We
      suggest that when templating femoral stem, this criterion "the TLT is less than 5
      mm" reduces some risks by inappropriate rotated radiograph.

PMID- 17522881
TI  - Three synchronized neoplasms of the female genital tract: an extraordinary
      presentation.
AB  - INTRODUCTION: We report a case of unusual co-existence of multiple primary
      neoplasms of female genital tract. CASE: A 62-year-old gravida 2, para 2 was
      referred with spotting and vaginal discharge for about 6 months. Fractionate
      curettage was performed and documented endocervical squamous cell carcinoma in
      situ. Subsequently total abdominal hysterectomy and bilateral salphingo
      oophorectomy was performed. Final pathological report demonstrated cervical
      squamous cell carcinoma, right ovarian Brenner tumor, left ovarian granulosa
      tumor and endometrial polyps. DISCUSSION: Multiple primary neoplasms of female
      genital tract is a well-recognized yet rare occurrence. Although the presented
      case is probably an incidental event, the pathogenesis of the neoplastic process
      affecting the tissues with different embryological origin needs further research
      and evaluation. It is important to distinguish multiple primary neoplasms from
      metastatic disease because of the fact that overall survival as well as treatment
      would vary considerably.

PMID- 17522882
TI  - Obstetric care of Jehovah's Witnesses: a 14-year observational study.
AB  - Over a 14-year period, the obstetric outcome of Jehovah's Witnesses in an inner
      city hospital was reviewed and the effect of refusal of blood on morbidity and
      mortality evaluated. Ninety women had 116 deliveries and of these, 24% were
      delivered by caesarean section, 10% had instrumental deliveries and 66% were
      normal vaginal deliveries. Postpartum haemorrhage of >1,000 mls occurred in 6%
      and postpartum anaemia was the commonest complication. The mean postdelivery
      haemoglobin (11.10 +/- 1.15 g/dl) was not significantly less from the mean
      predelivery haemoglobin level (11.81 +/- 1.62 g/dl) (P > 0.05, paired t test).
      The single maternal death occurred after caesarean hysterectomy, which when
      extrapolated, resulted in a 65-fold increased risk of maternal death compared to
      the national rate. The optimum management of pregnant women who decline
      transfusion is discussed.

PMID- 17522884
TI  - Effect of central corneal thickness on Goldmann applanation tonometry measures -
      a different result with different pachymeters.
AB  - PURPOSE: To assess whether the use of Orbscan pachymetry, as an alternative to
      ultrasound pachymetry, had an effect on the IOP-CCT relationship for Goldmann
      tonometry in normal human eyes. PATIENTS AND METHODS: The right eye of 50 healthy
      subjects, aged 19 to 82 years, were assessed by Orbscan (three scans), and then
      central corneal thickness (CCT) measured by ultrasound pachymetry (three
      readings) and Goldmann tonometry performed (three readings). RESULTS: Goldmann
      tonometry indicated average IOP values from 9.7 to 20 mm Hg (group mean 14.3 +/-
      2.5 mm Hg) that were highly highly correlated with ultrasound pachymetry (r =
      0.608, p < 0.001). Orbscan central zone pachymetry (2-mm sample zone) yielded
      higher values than ultrasound, averaging 0.591 +/- 0.044 mm compared to 0.523 +/-
      0.037 mm (p < 0.001), with the differences between the instruments being
      proportional to the average thickness (p < 0.001; r = 0.461). Notwithstanding,
      the Goldmann tonometry values were still highly correlated with the Orbscan
      central zone thickness data (r = 0.595, p < 0.001); but, due to the difference in
      the thickness data generated by the two pachymeters, the absolute slope of the
      IOP-CCT relationship was slightly less if Orbscan measures were used, with or
      without use of the acoustic factor. CONCLUSION: Orbscan measures of the thickness
      of a central corneal zone can be used to assess the impact of central corneal
      thickness on Goldmann tonometry data.

PMID- 17522883
TI  - Electron microscopic findings in levator muscle biopsies of patients with
      isolated congenital or acquired ptosis.
AB  - OBJECTIVE: Systemic mitochondriopathies as chronic progressive external
      ophthalmoplegia (CPEO) are frequently associated with ptosis. We investigated
      whether mitochondrial abnormalities in the levator muscle are also found in
      patients with isolated congenital or acquired ptosis showing no other signs of
      mitochondrial cytopathy. METHODS: Biopsies of levator muscle were taken during
      surgery from 24 patients with isolated congenital (group 1) or early-onset
      acquired ptosis (group 2). All patients were given a thorough clinical
      examination before and after surgery. Ultrathin muscle sections were examined by
      transmission electron microscopy. The findings were compared with biopsies from
      five patients with CPEO (positive control) and two patients with traumatic ptosis
      or pseudoptosis (negative control). RESULTS: The mean levator function equalled
      7.3 mm (range 4-10 mm) in group 1 and 12.8 mm (range 9-15 mm) in group 2. Eight
      out of 11 patients in group 1 and eight out of 13 patients in group 2 were found
      to have mitochondrial alterations such as megamitochondria, mitochondrial matrix
      alterations and abnormal cristae, similar to CPEO. Within group 1 and 2, no
      significant clinical differences were found between patients with and without
      mitochondrial abnormalities. CONCLUSION: Mitochondrial alterations were found in
      a surprisingly large proportion of levator biopsies from patients with isolated
      congenital or early-onset acquired ptosis. There was no statistically significant
      correlation between mitochondrial alterations and levator function. Our findings
      suggest that the ultrastructural assessment of mitochondria in the eyelid muscle
      is a valuable tool, and may guide further biochemical and mutation screening
      tests that will help to understand the etiopathology of this disease.

PMID- 17522885
TI  - Longitudinal study on potential neurotoxic effects of aluminium: I. Assessment of
      exposure and neurobehavioural performance of Al welders in the train and truck
      construction industry over 4 years.
AB  - OBJECTIVES: Previous cross sectional studies on potential neurotoxic effects of
      long-term aluminium exposures by aluminium welders lack clear interpretable
      results for methodological reasons. The present longitudinal study examined on
      the one hand the reliability and representativity of Al-biomonitoring as
      indicator of individual long-term exposure and on the other hand the long-term
      changes of neurobehavioural performance in Al welders in relation to Al exposure
      and neurobehavioural performance changes of a non-exposed control group. METHODS:
      The longitudinal study compared repeatedly measured exposure data and
      neurobehavioural data of 20, initially 44, male Al welders in the train and truck
      construction industry with data of a control group of similar age on the basis of
      three investigations over a period of 4 years. The repeated measurements of
      exposure included total dust in air as well as Al in pre- and post-shift plasma
      and urine samples. Neurobehavioural methods comprised symptoms, verbal
      intelligence, logic thinking, psychomotor behaviour, memory, and attention.
      Computer-aided tests from the Motor Performance Series (MLS) and the European
      Neurobehavioural Evaluation System (EURO-NES) were used. The characteristics of
      the biomonitoring data and the relationship to neurobehavioural data were
      examined with methods of correlation and regression analysis. The courses of
      neurobehavioural changes were analysed with multivariate covariance-analytical
      methods (MANCOVA) considering the covariates age, indicators of 'a priori'
      intelligence differences (education or 'premorbid' intelligence), and alcohol
      consumption (carbohydrate-deficient transferrin in plasma, CDT). RESULTS: The
      mean total dust load during welding, near to the routinely worn ventilated
      helmets, was in the range of 5-8 mg/m(3). The biomonitoring data of the welders
      (pre-shift: 88-140 microg Al/g creatinine in urine; 13-16 microg Al/l plasma)
      showed a high long-term stability but also sensitivity to acute shift dependent
      exposure changes. The Al welders who had been working in this profession at an
      average of 15 years showed no significantly increased symptom levels compared
      with the control group. Explorative regression and covariance analyses revealed
      neither a correlation between biomonitoring and performance variables nor a
      significant difference between Al-exposed and controls in the performance courses
      during the 4 years period. Explorative modelling indicated that the structure of
      neurobehavioural outcomes could be determined by possible indicators of
      intellectual 'a priori' (premorbid) differences between subjects but not by their
      exposure information. CONCLUSIONS: Compared to studies in the literature this
      study is characterized by relatively high and non-confounded Al exposure of the
      welders, a repeated-measurement design, and multivariate analyses. However, the
      long-term stable interindividual differences of internal Al exposure were not
      related to interindividual differences in neurobehavioural performances.
      Additionally, the lack of processual changes of neurobehavioural performances
      during the observation phase and the insignificant group differences do not make
      it very probable that degenerative processes caused by Al had happened before
      study onset or stopped just at this time point.

PMID- 17522886
TI  - Gender specific activation patterns of trunk muscles during whole body tilt.
AB  - Gender specific differences as evidenced in both anthropometric data and physical
      performance of healthy persons have been broadly demonstrated. Recently
      advancements in surface electromyography (SEMG) have shown possible differences
      in men's and women's muscle coordination patterns. However, quantitative
      information about gender related muscle co-ordination patterns are rare. This
      investigation was carried out to both verify if trunk muscle SEMG amplitude-force
      relationship differs between men and women and refine techniques of measurement
      and data analysis using SEMG. Thirty-one healthy volunteers (16 women, 15 men)
      were investigated during whole body tilt at angles from 5 degrees to 90 degrees
      (from quasi vertical to horizontal position). Subjects had to maintain body in
      body axis while their lower body was fixed and the upper body remained
      unsupported. SEMG was taken from five different trunk muscles of both sides
      simultaneously. At corresponding tilt angles women exhibited higher amplitude
      levels of their abdominal muscles in comparison to men, who were characterized by
      higher back muscle amplitudes. Abdominal muscles showed a non-linear SEMG
      amplitude-force relationship but differed between genders with more linearity in
      women. Back muscles showed a linear amplitude-force relationship with no
      differences between genders. Women were characterized by higher levels of co
      contraction of all investigated muscles. The data are in accordance with
      histological investigations, which already proved specific fiber distribution
      patterns in both abdominal and back muscles and gender related differences in
      relative area of Type 1 fibers of back muscles. The observed differences in SEMG
      force relationship for the abdominal muscles remain hypothetical because of lack
      of histological information.

PMID- 17522887
TI  - AtMTM1, a novel mitochondrial protein, may be involved in activation of the
      manganese-containing superoxide dismutase in Arabidopsis.
AB  - Mtm1p is essential for the posttranslational activation of manganese-containing
      superoxide dismutase (SOD2) in Saccharomyces cerevisiae; however, whether the
      same holds true for Arabidopsis thaliana is unknown. In this study, by using the
      yeast mtm1 mutant complementation method, we identified a putative MTM gene
      (AtMTM1, At4g27940) that is necessary for SOD2 activation. Further, analysis of
      SOD activity revealed that an SOD2 defect is rescued in the yeast mutant Y07288
      harboring the AtMTM1 gene. Related mRNA-level analysis showed the AtMTM1 gene is
      induced by paraquat but not by hydrogen peroxide, which indicates that this gene
      is related to the superoxide scavenger SOD. In addition, an AtMTM1::GFP fusion
      construct was transiently expressed in the protoplasts, and it was localized to
      the mitochondria. Furthermore, sequence deletion analysis of AtMTM1 revealed that
      the code region (amino acid (aa) 60-198) of Mtm1p plays an important role in
      localization of the protein to the mitochondria. Regulation of AtMTM1 gene
      expression was analyzed using a fusion construct of the 1,766 bp AtMTM1 promoter
      and the GUS (beta-glucuronidase) reporter gene. The screen identified GUS
      reporter gene expression in the developing cotyledons, leaves, roots, stems, and
      flowers but not in the siliques. Our results suggest that AtMTM1 encodes a
      mitochondrial protein that may be playing an important role in activation of
      MnSOD1 in Arabidopsis.

PMID- 17522888
TI  - Developmental control of Arabidopsis seed oil biosynthesis.
AB  - Arabidopsis transcriptional factors LEAFY COTYLEDON1 (LEC1), LEAFY COTYLEDON2
      (LEC2), FUSCA3 (FUS3), ABSCISIC ACID3 (ABI3), and ABSCISIC ACID5 (ABI5) are known
      to regulate multiple aspects of seed development. In an attempt to understand the
      developmental control of storage product accumulation, we observed the expression
      time course of the five transcripts. The sequential expression of these factors
      during seed fill suggests differentiation of their normal responsibilities. By
      extending the expression periods of the two early genes LEC1 and LEC2 in
      transgenic seeds, we demonstrated that the subsequent timing of FUS3, ABI3, and
      ABI5 transcripts depends on LEC1 and LEC2. Because a delayed onset or reduced
      level of FUS3 mRNA coincided with reduction of seed oil content in the transgenic
      seeds, the role of FUS3 in oil deposition was further examined. Analysis of
      published seed transcriptome data indicated that FUS3 transcript increased
      together with nearly all the plastidial fatty acid biosynthetic transcripts
      during development. The ability of FUS3 to rapidly induce fatty acid biosynthetic
      gene expression was confirmed using transgenic Arabidopsis seedlings expressing a
      dexamethasone (DEX)-inducible FUS3 and Arabidopsis mesophyll protoplasts
      transiently expressing the FUS3 gene. By accommodating the current evidence, we
      propose a hierarchical architecture of the transcriptional network in Arabidopsis
      seeds in which the oil biosynthetic pathway is integrated through the master
      transcriptional factor FUS3.

PMID- 17522889
TI  - Bone formation in cardiac valves: a histopathological study of 128 cases.
AB  - In a series of 1,177 patients with surgical valve resection, there were 128
      (10.9%) patients with the histological finding of bone and/or cartilage formation
      (bony metaplasia; heterotopic ossification) in the excised valve (119 aortic, 9
      mitral). The incidence was higher in men (12.8%) than in women (8.5%). The bony
      metaplasia was always associated with valvular calcification. The metaplastic
      changes were encountered in all types of calcific aortic valve disease (senile,
      bicuspid valve, post-rheumatic). The marrow of the heterotopic lamellar bone was
      mostly composed of adipose tissue. Frequently, it showed chronic inflammation
      with polyclonal plasmocytic infiltration. Complete haematopoiesis was present
      only rarely.

PMID- 17522890
TI  - Hodgkin's lymphoma in a patient with Jo-1 syndrome.
AB  - Jo-1 syndrome is an autoimmune disease with autoantibodies against the histidyl
      tRNA synthetase. Characteristic clinical findings include inflammatory myopathy
      and interstitial lung disease. We present the first case of a patient with Jo-1
      syndrome (positive Jo-1 autoantibodies, myositis, interstitial alveolitis) who
      developed Hodgkin's lymphoma of nodular-sclerosing type. Thus, patients with Jo-1
      syndrome and immunosuppressive therapy similar to other patients with autoimmune
      disease are at risk to develop lymphomas and should therefore be monitored
      carefully.

PMID- 17522891
TI  - Determination of pneumococcal serotypes/genotypes in nasopharyngeal secretions of
      otitis media children by multiplex PCR.
AB  - The appropriate clinical applications of pneumococcal polysaccharide vaccines
      against recent increases in antimicrobial resistant Streptococcus pneumoniae (S.
      pneumoniae) urgently require accurate analytical methodologies for determining
      and characterizing the serotypes. The results of current immunological
      determinations of serotypes with anti-capsular polysaccharide-specific sera are
      difficult to interpret in terms of quellung changes of the pneumococci. In this
      study, we applied the multiplex PCR technique for the rapid identification of
      pneumococci and simultaneous rapid determinations of their serotypes and
      genotypes that directly correlated with antimicrobial susceptibilities from
      nasopharyngeal secretions (NPS). Serogroups 6, 19F and 23F were the predominant
      capsular types of S. pnuemoniae in the NPS samples. Strains of serotypes 19F and
      23F frequently had mutations in pbp1a, pbp2x and pbp2b and expressed ermB and
      mefA; they also were mostly resistant to both penicillin G (PCG) and
      clarithromycin (CAM). Two NPS samples contained the strain of serotype 19F
      together with the strain of serotype 23F, although only the strain of serotype
      19F was identified by a conventional bacterial culture. Pneumococci were
      identified in six NPS samples and their serotypes determined by the multiplex
      PCR, while a conventional bacterial culture failed to identify the pathogens. Our
      findings suggest that PCR-based serotyping and genotyping can provide an accurate
      and rapid distribution of pneumococcal serotypes and antimicrobial resistance.
      The relatively minor populations in the nasopharynx may be determined using
      molecular techniques.

PMID- 17522892
TI  - Fasciola hepatica: the infectivity of cattle-origin miracidia had increased over
      the past years in central France.
AB  - A retrospective study on experimental infections of Galba truncatula, originating
      from four populations, was carried out to determine the infectivity of Fasciola
      hepatica miracidia in snails either subjected to single-miracidium or
      bimiracidial exposures in 2006 and to compare it with results found before 1990
      in other experiments using the same protocol. In single-miracidium infections,
      the prevalence of snail infection was significantly greater in 2006 than in
      experiments performed before 1980, while snail survival at day 30 postexposure
      showed insignificant differences. In bimiracidial infections, snail survival in
      two snail groups was significantly lower in 2006 than in experiments performed
      from 1981 to 1990, while insignificant differences were found for the other two
      populations of G. truncatula. Compared to results found between 1981 and 1990,
      the prevalence of snail infection did not significantly differ in 2006. In each
      population considered alone, the mean number of cercariae shed by infected snails
      did not significantly vary, whatever the date of experiment and the number of
      miracidia used for each exposure. The greater infectivity of F. hepatica
      miracidia towards snails might be the consequence of specific molecules such as
      triclabendazole used since 1990 to treat fasciolosis in cattle from central
      France.

PMID- 17522893
TI  - Ultrastructure of a spermatid transport system in the mature proglottids of
      experimental Taenia crassiceps (WFU strain).
AB  - In classical textbooks of parasitology, the mature proglottids of taeniids are
      depicted as structures in which the individual testis are connected to the vas
      deferens through the vas efferens system, usually depicted as a network of
      channels. From our morphological analyses of proglottids in the cestode Taenia
      crassiceps, we have been unable to identify this channel network. It is unclear
      how the spermatids are transported from the testes to the vas deferens, as is
      unresolved the location of the cells responsible for the production of
      testosterone (Leydig cells) or the possible equivalent of Sertoli cells,
      necessary for the differentiation process of these cells. In this experimental
      work, we have examined the ultrastructure of tissues in the vicinity of the vas
      deferens in mature proglottids obtained from the intestines of hamsters infected
      with cysticerci from the peritoneum of infected mice. Worm tissues were fixed,
      processed, and sectioned for transmission electron microscopy. Significant areas
      of the testis epithelia emitted cytoplasmic projections surrounded by
      extracellular matrix, where they appear as septated pockets enclosing free
      axonemes and spermatids. Vas efferens walls are made up of nucleated cells with
      cytoplasm annealing to each other through cell membrane junctions. Lodged between
      the junctions are membrane-bound pouches with dense granules found as aggregates
      or aligned in a semicircular array. The efferens wall exhibits numerous
      spermatids emerging into the lumen, an observation that suggests the epithelial
      wall may have the maturing functions of Sertoli cells of vertebrates. Large cells
      adjacent to the vas efferens contained prominent rough endoplasmic reticulum and
      large mitochondria, characteristics described for Leydig cells of vertebrates.
      Our observations suggest that taeniid spermatids are either transported from the
      testes to the vas system by epithelial pockets or that the epithelial pockets may
      be cross-sections of a highly coiled vas efferens system.

PMID- 17522895
TI  - Selective visualisation of sensory receptors in the smooth muscle layer of ex
      vivo airway whole-mounts by styryl pyridinium dyes.
AB  - Recently, we established the location, morphology and neurochemical coding of
      vagal smooth-muscle-associated airway receptors (SMARs) in rat lungs. These
      receptors were characterised as branching laminar terminals that originated from
      myelinated nerve fibres and were intercalated between airway smooth-muscle
      bundles. To allow the direct physiological examination of these receptors, the
      present investigation aimed at visualising SMARs in airway whole-mounts of rat
      and mouse lungs ex vivo. Short incubation with various styryl pyridinium dyes
      (AM1-43, FM2-10, FM4-64 or 4-Di-2-ASP) gave a highly selective fluorescent
      visualisation of both laminar nerve terminals and myelinated fibres from which
      they originated throughout the intrapulmonary airway tree in mouse and in rat.
      The reliable and specific labelling of SMARs ex vivo with these lipophilic
      membrane dyes was confirmed via immunostaining for protein gene-product 9.5 and
      vesicular glutamate transporters. Similar to the intrapulmonary location of NEBs,
      these SMARs appeared to be even more explicitly located near airway bifurcations.
      Both the trachealis muscle and the smooth-muscle bundles of extrapulmonary
      bronchi were also shown to contain laminar nerve terminals that were
      morphologically similar to the SMARs reported in the intrapulmonary airways.
      Thus, this study provides an in-vitro model enabling, for the first time, the
      fast and reliable visualisation of SMARs and the myelinated nerve fibres from
      which they originate in airway whole-mount preparations ex vivo. As such, this
      model opens up further perspectives and creates a valid basis for direct
      physiological measurement and manipulation of the individually identified airway
      receptors.

PMID- 17522894
TI  - Random homologous pairing and incomplete sister chromatid alignment are common in
      angiosperm interphase nuclei.
AB  - The chromosome arrangement in interphase nuclei is of growing interest, e.g., the
      spatial vicinity of homologous sequences is decisive for efficient repair of DNA
      damage by homologous recombination, and close alignment of sister chromatids is
      considered as a prerequisite for their bipolar orientation and subsequent
      segregation during nuclear division. To study the degree of homologous pairing
      and of sister chromatid alignment in plants, we applied fluorescent in situ
      hybridisation with specific bacterial artificial chromosome inserts to interphase
      nuclei. Previously we found in Arabidopsis thaliana and in A. lyrata positional
      homologous pairing at random, and, except for centromere regions, sister
      chromatids were frequently not aligned. To test whether these features are
      typical for higher plants or depend on genome size, chromosome organisation
      and/or phylogenetic affiliation, we investigated distinct individual loci in
      other species. The positional pairing of these loci was mainly random. The
      highest frequency of sister alignment (in >93% of homologues) was found for
      centromeres, some rDNA and a few other high copy loci. Apparently, somatic
      homologous pairing is not a typical feature of angiosperms, and sister chromatid
      aligment is not obligatory along chromosome arms. Thus, the high frequency of
      chromatid exchanges at homologous positions after mutagen treatment needs another
      explanation than regular somatic pairing of homologues (possibly an active search
      of damaged sites for homology). For sister chromatid exchanges a continuous
      sister chromatid alignment is not required. For correct segregation, permanent
      alignment of sister centromeres is sufficient.

PMID- 17522896
TI  - Mouse CD24 is required for homeostatic cell renewal.
AB  - Under physiological conditions, some adult tissues retain a capacity for self
      renewal. This property is attributable to the proliferation and differentiation
      of stem, transit-amplifying, and differentiating cells, which are regulated by
      cell-cell or cell-matrix interactions or by secreted factors. By gain and loss of
      function experiments, we demonstrate the involvement of mouse CD24 (mouse cluster
      of differentiation 24), which is a glycosyl phosphatidylinositol (GPI)-anchored
      cell-surface glycoprotein, in the regulation of homeostatic cell renewal. BrdU
      incorporation observations, at optical and electron-microscopic levels, have
      revealed increased cell proliferation in the developing brain and in the
      epithelia of mCD24-deleted mice. We have observed ectopic proliferative cells in
      the suprabasal layers of the mutant skin leading to a general disruption of basal
      and suprabasal layers. By contrast, ectopic mCD24 expression mediated by
      retroviral infection of the embryonic brain leads to a decreased number of
      clusters of cells generated in the progeny. Together, these results and our
      previous published data indicate that mCD24 contributes to the regulation of the
      production of differentiated cells by controlling the
      proliferation/differentiation balance between transit-amplifying and committed
      differentiated cells.

PMID- 17522897
TI  - [Positron emission tomography in pain research. From the structure to the
      activity of the opiate receptor system].
AB  - Over the last decades, functional imaging studies have fostered our knowledge of
      cerebral pain processing in humans. A lively interest has been focussing on
      possible opioidergic mechanisms of pain transmission and modulation. Today,
      reliable knowledge of the in vivo distribution of opioid receptors in healthy
      human subjects is available from positron emission tomography (PET) studies of
      opioidergic neurotransmission. Gender dependent differences in receptor
      distribution and ligand metabolism have been demonstrated. Moreover, an
      increasing number of studies are reporting alterations in receptor distribution
      patterns in states involving painful diseases. Various acute painful challenges
      have also been shown to induce measurable changes in receptor availability in
      multiple brain areas. The perigenual anterior cingulate cortex (ACC) has been
      identified as one brain region with a major impact on opioidergic pain
      modulation. Thereby, the ACC apparently executes cortical top-down control on
      brainstem structures in (exogenous) pharmacological opioid analgesia. In
      addition, accumulating evidence suggests that non-pharmacological treatment
      approaches also utilize similar endogenous opioid dependent pathways to exert
      pain modulation. This article summarizes our current knowledge of PET studies of
      the opioidergic system and outlines future perspectives.

PMID- 17522898
TI  - [Multidimensional pain assessment in patients with dementia].
AB  - BACKGROUND: It is well known that patients with dementia complain less about pain
      and receive fewer analgesics than other patients. The question arises of whether
      disorders associated with dementia change the processing of pain. METHODS: A
      total of 20 patients with dementia and 40 patients with mild cognitive impairment
      (MCI) as well as 40 healthy control subjects were investigated for their
      subjective (category scale), facial (FACS) and motor (R-III reflex) pain
      responses to mechanical and electrical stimuli. RESULTS: Patients with dementia
      did not rate the intensity of the stimuli differently; however, they were less
      frequently capable of providing ratings. At equal levels of stimulus intensity,
      demented patients showed stronger facial responses. The R-III reflex thresholds
      were lowered in demented patients. MCI patients appeared only slightly changed.
      CONCLUSIONS: Our findings suggest that the processing of acute noxious stimuli is
      intensified in patients with dementia. Against the background of a reduced
      prescription of analgesics, an under-treatment of pain in patients with dementia
      might be the consequence.

PMID- 17522899
TI  - Repeatability of ultrasonic determination of gingival thickness.
AB  - The aim of the present study was to assess the degree of disagreement of
      ultrasonic measurements of gingival thickness at different teeth. Gingival
      thickness was determined in 33 volunteers with plaque-induced gingivitis.
      Facial/buccal gingiva was measured at the level of the gingival sulcus depth.
      Measurements were repeated after 2 and 4 weeks. A repeated measures, two-level
      (occasion, subject), variance components model revealed a within-subject variance
      of 0.187 mm(2) resulting in a repeatability coefficient of 1.20 mm. When modeling
      level 1 (occasion) variance as a function of tooth type, respective error terms
      were used for calculating 95% repeatability coefficients for different teeth.
      Unreliable measurements were largely confined to upper and lower second and third
      molars. Error terms were lowest (0.03-0.05) at upper canines and first premolars
      as well as lower anterior teeth and premolars, where repeatability coefficients
      of 0.5 to 0.6 mm could be estimated. It was concluded that performance of the
      device was best at certain tooth types with rather thin gingiva. The present
      resolution and rather high degree of disagreement may preclude, however,
      detection of minute increases in thickness in the micrometer range, which seem to
      occur during gingivitis.

PMID- 17522900
TI  - Radiographic evaluation of the chronological development of permanent dentition
      in children infected with HIV.
AB  - The objective of this study is to determine if there is an association between
      HIV infection in children and alterations in the chronological development of
      permanent dentition detectable by radiographic examination. The sample comprised
      two groups of children: (1) 50 children infected with HIV by vertical
      transmission and (2) 50 healthy children. The groups were paired according to
      age, sex, race, and socioeconomic level. After obtaining a panoramic radiograph,
      the stages of tooth calcification and the frequency of subjects showing alveolar
      eruption of the first and second mandibular permanent molars were determined.
      There was no significant difference in stages of tooth calcification and
      frequency of subjects showing alveolar eruption of the permanent molars between
      the groups (P > 0.05). Children infected with HIV by the vertical route showed
      upon radiographic examination stages of tooth calcification and alveolar eruption
      compatible with normal patterns. There is no association between HIV infection
      and alterations in the chronological development of the permanent teeth,
      detectable radiographically, in children infected by vertical transmission.

PMID- 17522901
TI  - Levels of gingival tissue platelet activating factor after conventional and
      regenerative periodontal surgery.
AB  - The hypothesis, a relationship between gingival tissue platelet activating factor
      (PAF) levels and healing after periodontal surgery, was tested by measuring PAF
      levels in gingival tissues collected from sites that had undergone flap surgery
      and guided tissue regeneration (GTR) or flap surgery alone. Using a split-mouth
      design, 20 intrabony defects were randomly assigned to treatment with flap
      surgery and GTR (group 1) or with flap surgery alone (group 2). Gingival tissue
      samples were obtained at surgery (baseline) and at 6-month follow-up evaluation
      visit. One half of each sample was used for analysis of PAF levels by high
      performance liquid chromatography, and the other half of the sample was used for
      histomorphometric analysis that included measurements of number and diameter of
      blood vessels. PAF levels and diameter of blood vessels were significantly
      decreased (p < 0.01), and the number of blood vessels was significantly increased
      (p < 0.05) in both groups after 6 months compared to the baseline values.
      Postoperative number of blood vessels were significantly higher in group 1 (p <
      0.05), whereas there was no significant difference in postoperative PAF levels
      between the two groups (p > 0.05). Based on the reported results, it is suggested
      that a decrease in gingival PAF levels might be found after conventional and
      regenerative periodontal surgery.

PMID- 17522903
TI  - Mucosal secretion changes during radiotherapy in the oral cavity.
AB  - Mucositis in the oral cavity is a serious complication during radiation therapy
      for head and neck cancer, causing local discomfort and pain. In severe cases,
      hospitalization and interruption of radiotherapy may be necessary. The
      pathogenesis of this mucositis is not clear. With the purpose of getting more
      understanding of the pathogenesis of the mucositis, we examined the mucosal
      secretion from ten patients during radiotherapy with an imprint technique. In the
      secretion we studied the cellular composition and cellular function. In eight of
      ten treated patients the numbers of granulocytes increased in the secretion after
      2 weeks of radiation therapy. The granulocytes, however, did not show any signs
      of phagocytosis. The patients all developed mucositis. We propose that the
      granulocytes in the secretion might play an important role in the development of
      mucositis during radiotherapy.

PMID- 17522902
TI  - Antifungal susceptibility of Candida albicans biofilms on titanium discs with
      different surface roughness.
AB  - Although it is well known that fungal biofilms have increased resistance to
      antimicrobial agents, limited information is available on the formation of
      candidal biofilms on implant surfaces with different surface roughness and their
      resistance to conventional antifungal therapy. In the current study, the effect
      of increasing the surface roughness of titanium discs on the susceptibility of
      Candida albicans biofilms to amphotericin B was determined. Grade I commercially
      pure titanium discs were sandblasted with 99.6% aluminium oxide of different grit
      sizes, producing surface roughness of 0.90, 1.88 and 3.82 microm (Groups A, B and
      C), respectively (P < 0.001). The antifungal susceptibility of C. albicans
      biofilm grown on different Ti discs was determined using XTT assay. The 50%
      reduction in metabolic activity (50% RMA) of planktonic C. albicans (0.5
      microg/mL) was much lower than those from Groups A, B and C (2, 16, 2 microg/mL,
      respectively), while the 50% RMA from Group B was three-fold higher than those
      from Groups A and C. In conclusion, difference in titanium surface roughness was
      associated with variations in the antifungal resistance of the candidal biofilm.
      Group C appeared to have an optimum surface roughness for biofilm resistance.

PMID- 17522905
TI  - An unusual cause of small bowel obstruction: CT diagnosis of dried apricots.

PMID- 17522906
TI  - A rare complication of acute cholecystitis: transhepatic perforation associated
      with massive intraperitoneal hemorrhage.
AB  - A 2 to 11% of the patients with acute cholecystitis that will develop gallbladder
      perforation and massive intraperitoneal hemorrhage as a result of perforation
      will rarely be seen. Massive intraperitoneal hemorrhage associated with the
      transhepatic perforation is very uncommon. By this article, we anticipate
      presenting clinical and radiological findings in a case that has acute
      cholecystitis with massive intraperitoneal hemorrhage associated with
      transhepatic perforation.

PMID- 17522907
TI  - Traumatic sternal segment dislocation in a 19-month-old.
AB  - Sternal fractures in the pediatric population are uncommon. Traumatic sternal
      segment dislocation is even more unusual. Such injuries are typically considered
      to be the result of child abuse, until proven otherwise. A review of the few case
      reports documenting pediatric sternal segment dislocation, and the current
      report, demonstrate that this injury may, in fact, be more benign than previously
      considered. It is easily recognized with appropriate imaging, and treatment may
      only require observation, unless symptoms are severe enough to warrant surgical
      intervention.

PMID- 17522908
TI  - Acute rhabdomyolysis of the soleus muscle induced by a lightning strike: magnetic
      resonance and scintigraphic findings.
AB  - Among natural disasters, a lightning strike is a rare but potentially life
      threatening phenomenon. If victims survive a cardiac arrest due to instantaneous
      passage of an exceptionally high voltage electric charge through the whole body,
      they may be afflicted with various complications such as muscle necrosis
      resulting in acute renal failure. In this article, we report a case of a 54-year
      old man with acute rhabdomyolysis of the left soleus muscle associated with a
      lightning strike. T2-weighted and short-tau inversion recovery MR images showed a
      high signal intensity in the left soleus muscle. A whole-body bone scintigram
      showed abnormal uptakes in the left soleus muscle and the dorsal aspect of the
      left foot. MR and scintigraphic evaluations were very useful in depicting the
      site and extent of muscle damage. Since the patient showed a surprisingly high
      level of serum creatine kinase, the added information was very valuable for
      determining the patient's management.

PMID- 17522909
TI  - Parosteal lipoma associated with an underlying osteochondroma arising from the
      hallux.
AB  - Parosteal lipomas are rare benign tumours of mature adipose tissue that arise in
      continuity with the underlying bone. These lesions represent less than 0.3% of
      all lipomas and commonly arise in the femur, tibia, humerus and radius. There
      have been no reported cases of such lesions arising in the foot. Hence, we report
      the first case of a parosteal lipoma arising in the great toe in association with
      an underlying osteochondroma.

PMID- 17522911
TI  - Laparoscopic subtotal splenectomy in hereditary spherocytosis.

PMID- 17522912
TI  - Endoloop-assisted polypectomy for large peduncolated colorectal polyps.

PMID- 17522913
TI  - Pediatric robotic surgery: A single-institutional review of the first 100
      consecutive cases.
AB  - BACKGROUND: Robotic surgery is a new technology which may expand the variety of
      operations a surgeon can perform with minimally invasive techniques. We present a
      retrospective review of our first 100 consecutive robotic cases in children.
      METHODS: A three-arm robot was used with one camera arm and two instrument arms.
      Additional accessory ports were utilized as necessary. Two different attending
      surgeons performed the procedures. RESULTS: Twenty-four different types of
      procedures were completed using the robot. The majority of the procedures (89%)
      were abdominal procedures with 11% thoracic. No urology or cardiac procedures
      were performed. Age ranged from 1 day to 23 years with an average age of 8.4
      years. Weight ranged from 2.2 to 103 kg with a median weight of 27.9 kg. Twenty
      two patients were less than 10.0 kg. Examples of cases included gastrointestinal
      (GI) surgery, hepatobiliary, surgical oncology, and congenital anomalies. The
      overall majority of cases had never been performed minimally invasively by the
      authors. The overall intraoperative conversion rate to open surgery was 13%. One
      case (1%) was converted to thoracoscopic because of lack of domain for the
      articulating instruments. No conversions or complications occurred as a result of
      injuries from the robotic instruments. Interestingly, four abdominal cases were
      converted to open surgery due to equipment failures or injuries from standard
      laparoscopic instruments used through non-robotic accessory ports. CONCLUSIONS:
      Robotic surgery is safe and effective in children. An enormous variety of cases
      can be safely performed including complex cases in neonates and small children.
      Simple operations such as cholecystectomies have minimal advantages by using
      robotic technology but can serve as excellent teaching tools for residents and
      newcomers to this form of minimally invasive surgery (MIS). The technology is
      ideal for complex hepatobiliary cases and thoracic surgery, particularly solid
      chest masses.

PMID- 17522914
TI  - Laparoscopically assisted reversal of Hartmann's procedure.

PMID- 17522915
TI  - Origami using da Vinci surgical system.

PMID- 17522916
TI  - Intraoperative fluoroscopy vs. intraoperative laparoscopic ultrasonography for
      early colorectal cancer localization in laparoscopic surgery.
AB  - BACKGROUND: In colorectal cancer (CRC) surgery, precise tumor localization is
      important for oncologically correct surgery and adequate tumor and lymph node
      resection margins. During laparoscopic surgery it is difficult to localize early
      CRC. The aim of this study was to compare the usefulness of two tumor
      localization techniques; intraoperative fluoroscopy and intraoperative
      laparoscopic ultrasonography. METHODS: Seventeen patients with CRC necessitating
      preoperative marking were alternately allocated to either the fluoroscopy (F)
      group (n = 8) or the laparoscopic ultrasonography (LU) group (n = 9). A three
      step technique was used. At first lesions were localized preoperatively by
      metallic clips that were colonoscopically applied proximally and distally to the
      tumor site. Second, computed tomography (CT) colonography was taken to obtain
      preoperative staging. The location of the metallic clips was confirmed by CT
      colonography, preoperatively. Third, in the F group, intraoperative fluoroscopy
      was performed to localize the applied clips. In the LU group, the applied clips
      were detected from the serosal aspect of the colon using intraoperative
      laparoscopic ultrasonography. RESULTS: In all patients, colonoscopic metallic
      clips were successfully applied and preoperative CT colonography correctly
      detected the location of the tumor. Marking sites were detected precisely using
      intraoperative fluoroscopy or intraoperative laparoscopic ultrasonography in all
      cases, without complications. The mean detection time was 15.8 minutes in the F
      group and 7.0 minutes in the LU group (p = 0.005). In the LU group, two cases
      were technically difficult because of interruption of the ultrasound by
      intestinal air. CONCLUSIONS: Both intraoperative fluoroscopy and intraoperative
      laparoscopic ultrasonography are safe and accurate techniques for intraoperative
      localization of early CRC. With regard to detection time, intraoperative
      laparoscopic ultrasonography is superior to intraoperative fluoroscopy. However,
      when there is a massive amount of intestinal air, intraoperative laparoscopic
      ultrasonography is cumbersome in localizing the lesion. Computed tomography
      colonography is useful for preoperative tumor localization and might be effective
      for shortening detection time during surgery.

PMID- 17522917
TI  - Factors affecting the number of lymph nodes retrieved in colorectal cancer
      specimens.
AB  - BACKGROUND: Staging of colorectal cancer is dependent on the number of lymph
      nodes in a surgical specimen that are positive for metastatic cancer. It is
      generally recommended that a minimum of 12 lymph nodes be examined to ensure
      adequate staging. It is unclear which factors specifically contribute to
      variation in the number of lymph nodes retrieved from surgical specimens. This
      study aims to understand the factors affecting the number of lymph nodes
      identified in surgical colorectal cancer specimens. METHODS: A total of 264
      retrospectively collected cases of colorectal cancer surgically treated at the
      University Health Network in Toronto from 2004 to 2006 were analyzed. We used
      univariate analyses of variance (ANOVA), and univariate and multivariable linear
      and logistic regression analyses to study variation in the lymph node number
      associated with a variety of explanatory variables. RESULTS: The average number
      of lymph nodes retrieved per case was 18.1, with 70 (26.5%) cases containing
      fewer than 12. Variation in the lymph node number was greatest between different
      pathology assistants (p = or< 0.001). The mean number of nodes retrieved by
      different pathology assistants ranged from 12.6 to 29.7. On average, surgery for
      recurrent cancer removed 6.0 (95% CI 1.2 to 10.9, p = 0.02) fewer lymph nodes
      than for primary cancer. Each additional year of patient age was associated with
      retrieval of 0.1 (95% CI 0.04 to 0.2, p = 0.005) fewer nodes, and rectal cancer
      specimens had 2.7 (95% CI 0.04 to 5.4, p = 0.05) fewer lymph nodes than colon
      cancer specimens. CONCLUSION: Most of the variation in the number of lymph nodes
      identified in surgical specimens from colorectal cancer operations was accounted
      for by differences between pathology assistants.

PMID- 17522918
TI  - Do elderly patients benefit from laparoscopic colorectal surgery?
AB  - BACKGROUND: The steadily increasing age of the population mandates that potential
      benefits of new techniques and technologies be considered for older patients.
      AIM: To analyze the short-term outcomes of laparoscopic (LAP) colorectal surgery
      in elderly compared to younger patients, and to patients who underwent laparotomy
      (OP). METHODS: A retrospective analysis of patients who underwent elective
      sigmoid colectomies for diverticular disease or ileo-colic resections for benign
      disorders; patients with stomas were excluded. There were two groups: age < 65
      years (A) and age >or= 65 years (B). Parameters included demographics, body mass
      index (BMI), length of operation (LO), incision length (LI), length of
      hospitalization (LOS), morbidity and mortality. RESULTS: 641 patients (M/F -
      292/349) were included between July 1991 and June 2006; 407 in group A and 234 in
      group B. There were significantly more LAP procedures in group A (244/407 - 60%)
      than in group B (106/234 - 45%) - p = 0.0003. Conversion rates were similar:
      61/244 (25%) in group A, and 25/106 (24%) in group B (p = 0.78). There was no
      difference in LO between the groups in any type of operation. LOS was shorter in
      patients in group A who underwent OP: 7.1 (3-17) days versus 8.7 (4-22) days in
      group B (p <0.0001), and LAP: 5.3 (2-19) days versus 6.4 (2-34) days in group B
      (p = 0.01). In both groups LOS in the LAP group was significantly shorter than in
      OP group. There were no significant differences in major complications or
      mortality between the two groups; however, the complication rates in the OP
      groups were significantly higher than in LAP and CON combined (p = 0.003).
      CONCLUSIONS: Elderly patients who undergo LAP have a significantly shorter LOS
      and fewer complications compared to elderly patients who undergo OP. Laparoscopy
      should be considered in all patients in whom ileo-colic or sigmoid resection is
      planned regardless of age.

PMID- 17522919
TI  - Peritoneal and systemic pH during pneumoperitoneum with CO2 and helium in a pig
      model.
AB  - BACKGROUND: Local peritoneal effects of laparoscopic gases might be important in
      peritoneal biology during and after laparoscopic surgery. The most commonly used
      gas, CO(2), is known to be well tolerated, but also causes changes in acid-base
      balance. Helium is an alternative gas for laparoscopy. Although safe, it is not
      widely used. In this study a method for monitoring peritoneal pH during
      laparoscopy was evaluated and peritoneal pH during CO(2) and helium
      pneumoperitoneum was studied as well as its systemic reflection in arterial pH.
      METHODS: For these experiments 20 pigs were used, with ten exposed to
      pneumoperitoneum with CO(2), and ten to helium. Peritoneal and sub-peritoneal pH
      were continuously measured before and during gas insufflation, during a 30-minute
      period with a pneumoperitoneum and during a 30-minute recovery period. Arterial
      blood-gases were collected immediately before gas insufflation, at its
      completion, at 30 minutes of pneumoperitoneum and after the recovery period.
      RESULTS: Peritoneal pH before gas insufflation was in all animals 7.4. An
      immediate local drop in pH (6.6) occurred in the peritoneum with CO(2)
      insufflation. During pneumoperitoneum pH declined further, stabilising at 6.4,
      but was restored after the recovery period (7.3). With helium, tissue pH
      increased slightly (7.5) during insufflation, followed by a continuous decrease
      during pneumoperitoneum and recovery, reaching 7.2. Systemic pH decreased
      significantly with CO(2) insufflation, and increased slightly during helium
      insufflation. Systemic pH showed co-variation with intra-peritoneal pH at the the
      end of insufflation and after 30 minutes of pneumoperitoneum. CONCLUSIONS:
      Insufflation of CO(2) into the peritoneal cavity seemed to result in an immediate
      decrease in peritoneal pH, a response that might influence biological events.
      This peritoneal effect also seems to influence systemic acid-base balance,
      probably due to trans-peritoneal absorption.

PMID- 17522920
TI  - Endoscopic bilateral neck exploration versus quick intraoperative parathormone
      assay (qPTHa) during endoscopic parathyroidectomy: A prospective randomized
      trial.
AB  - BACKGROUND: Quick intraoperative parathormone assay (qPTHa) during
      paratyroidectomy has become a standard procedure for patients with primary
      hyperparathyroidism (PHPT). This paper aims to compare endoscopic bilateral neck
      exploration (BE) versus focused parathyroidectomy plus qPTHa during minimally
      invasive video-assisted parathyroidectomy (QM). The endpoints of the study are
      the mean operative time and outcome of the surgical procedure (PTH and calcemia
      normalization at one and six months postoperatively). METHODS: Forty patients
      with PHPT, positive to preoperative localization studies (ultrasonography
      evaluation and (99)Tc-MIBI scan) for a single parathyroid adenoma, were randomly
      allotted into two groups. In the first group (QM), 20 patients (17 women, three
      men, mean age 57.6 years) underwent focused endoscopic parathyroidectomy (MIVAP
      tecnicque) plus qPTHa . In the second group (BE) 20 patients (17 women, three
      men, mean age 59.6 years) underwent endoscopic parathyroidectomy plus bilateral
      exploration in order to check the integrity of the remaining glands. RESULTS:
      There were no significant differences between groups at baseline. No conversion
      to cervicotomy was required. No postoperative complications were reported. The
      mean operative time was 32.0 vs 33.1 min [BE and QM group respectively, p = not
      significant (ns)]. A second macroscopically enlarged gland was removed in four
      patients in the BE group. Only one out of four glands was reported to be
      hyperplastic in the final histology. All patients were discharged on the first
      postoperative day. Calcemia levels were normalized in all patient of both groups,
      despite persistently high level of serum PTH in one patient in the QM group.
      CONCLUSIONS: BE can be performed endoscopically, avoiding both the time necessary
      for qPTHa and its cost, with the same effectiveness, but might in few cases lead
      to the unjustified removal of parathyroid glands slightly enlarged but not
      necessarily pathologic.

PMID- 17522921
TI  - Video-assisted breast surgery and sentinel lymph node biopsy guided by three
      dimensional computed tomographic lymphography.
AB  - BACKGROUND: Video-assisted breast surgery (VABS) is a less invasive and
      aesthetically better option for benign and malignant breast diseases and for
      sentinel lymph node biopsy (SLNB). The authors have performed 150 VABS procedures
      since December 2001. They have examined the usefulness of three-dimensional
      computed tomographic (3D-CT) lymphography for detecting sentinel lymph nodes
      (SLNs) precisely, as well as the cosmetic and treatment results of VABS. METHODS:
      In this study, VABS was performed with a 2.5-cm skin incision in the axilla or
      periareola (1 cm in the axilla for SLNB), using a retraction method, for mammary
      gland resection, SLNB, axillary lymph node dissection, and breast reconstruction
      under video assistance. On the day before the surgery, 3D-CT lymphography was
      performed to mark SLN on the skin. Above the tumor and near the areola, 2 ml of
      Iopamiron 300 was injected subcutaneously. A 16-channnel multidetector-row
      helical CT scan image was taken after 1 min and reconstructed to produce a 3D
      image. Sentinel lymph node biopsy was performed by the VABS technique using the
      Visiport. RESULTS: The VABS procedure was performed for 19 benign and 131
      malignant diseases, and 115 SLNBs (74 with 3D-CT) were performed. The SLNs were
      shown precisely by 3D-CT lymphography, as proved by a case of lymph node
      metastasis, in which accurate relationships between lymph ducts and SLNs were
      shown. These were classified into four patterns: a single duct to single node (40
      cases), multiple ducts to a single node (13 cases), a single duct to multiple
      nodes (1 case), and multiple ducts to multiple nodes (12 cases). The SLNB
      procedure can be performed safely by 3D-CT lymphography and less invasively by
      VABS. CONCLUSIONS: The findings show that 3D-CT lymphography is useful for
      performing precise SLNB using VABS.

PMID- 17522922
TI  - Outcome of laparoscopic ventral hernia repair in morbidly obese patients with a
      body mass index exceeding 35 kg/m2.
AB  - BACKGROUND: Laparoscopic ventral hernia repair (LVHR) for morbidly obese patients
      with a body mass index (BMI) exceeding 35 kg/m(2) has not been well investigated.
      METHODS: Hernia recurrence was evaluated by surveillance computed tomography. A p
      value less than 0.05 was considered significant. RESULTS: Between 2003 and 2006,
      LVHR was attempted for 27 patients with a BMI exceeding 35 kg/m(2). There was one
      conversion to open surgery (3.7%). The 27 patients included 8 men (29.6%) and 19
      women (70.4%) with a mean age of 48 years (range, 33-73 years). The mean BMI was
      46.9 kg/m(2) (range, 35-70 kg/m(2)). Nine patients (33%) were superobese (BMI >
      50 kg/m(2)), and five patients (22.7%) underwent emergency LVHR because of small
      bowel obstruction. Concomitant LVHR with laparoscopic gastric bypass (LGB) was
      performed for 13 patients (48%). Primary, incisional, or recurrent incisional
      ventral hernia was present in 7 (26%), 15 (55%), and 5 (19%) patients,
      respectively. A large hernia (>50 cm(2)) was found in 20 patients (74%). The mesh
      used was porcine submucosal small intestine extracellular matrix for 15 patients
      (57%), Gore-Tex for 9 patients (35%), and Composix for 2 patients (8%). The mean
      hernia size was 158 cm(2 )(range, 12-806 cm(2)), and the mean mesh size was 374
      cm(2) (range, 117-2,400 cm(2)). The mean operative time was 190 min (range, 80
      480 min), and the mean hospital length of stay (LOS) was 3.6 days (range, 1-11
      days). Minor or major complications occurred in seven patients (25.9%), and five
      patients (18.5%) experienced recurrence during a mean follow-up period of 14.9
      months (range, 3-32 months). Emergency setting, BMI, concomitant LGB, hernia
      type, hernia size, and mesh type had no statistically significant effect on
      operative time, LOS, morbidity, or recurrence rates. CONCLUSIONS: For morbidly
      obese patients, LVHR is safe and effective, but it is associated with higher
      likelihood of recurrence, and patients should be appropriately informed.

PMID- 17522923
TI  - Minimizing bladder injury in laparoscopically assisted vaginal hysterectomy among
      women with previous cesarean sections.
AB  - BACKGROUND: This study demonstrated a method to prevent bladder injury during
      laparoscopically assisted vaginal hysterectomy (LAVH) to patients with
      vesicocervical adhesion after previous cesarean deliveries. METHODS: Between July
      2004 and July 2005, 50 women with vesicocervical adhesion who had given birth by
      cesarean delivery underwent LAVH. To minimize the chance of bladder injury,
      transvaginal lateral intervention was used to enter the anterior cul-de-sac
      during laparoscopic intrafascial hysterectomy. The lateral windows of the
      vesicocervical space were opened first. Usually, the potential spaces lateral to
      the adhesions could be developed easily by blunt finger dissection. Once adequate
      lateral spaces were created, an index finger was swept medially to define the
      margin of the midline adhesions secondary to the cesarean delivery scar. Under
      direct vision and finger guidance, the dense adhesions were dissected with more
      confidence and safety. Subsequently, the bladder was pushed gently aside to avert
      unexpected tearing or injury along the intrafascial hysterectomy. Because the
      vesico-uterine fold had been cut open previously under laparoscopy, the anterior
      cul-de-sac could be entered without much resistance. RESULTS: The average age of
      the patients was 45 +/- 7 years, and the extirpated uterine weight was 323 +/-
      170.8 g (range, 85-730 g). Intraoperatively, the mean operation time was 124.6 +/
      28.5 min (range, 80-235 min), and the average blood loss was 79.1 +/- 47.8 ml
      (range, 20-250 ml). The mean intramuscular meperidine requirements were 1.2 +/-
      0.8 ampules (range, 0-2 ampules) (1 ampule = 50 mg), and the average hospital
      stay was 3.2 +/- 0.9 days (range, 2-5 days). Of these 50 patients, 24 (48%) had
      one, 22 (44%) had two, and 4 (8%) had three previous cesarean deliveries. No
      bladder injury occurred among the patients, and there was no other complication.
      CONCLUSION: Transvaginal lateral intervention may help to minimize bladder
      injuries during LAVH for patients with previous cesarean deliveries.

PMID- 17522924
TI  - Percutaneous endoscopic gastrostomy with T-bar fixation in children and infants.
AB  - BACKGROUND: The standard for placement of pediatric gastrostomy tubes has been
      percutaneous endoscopic gastrostomy (PEG) using the Ponsky "pull" technique. This
      study evaluated the safety and efficacy of PEG placement using the "push"
      technique with T-bar fixation in pediatric patients. This technique generally is
      limited to the adult population. With this technique, endoscopy is performed. The
      stomach is insufflated, and the anterior abdominal wall is transilluminated. T
      bar fasteners are sequentially deployed to secure the stomach to the anterior
      abdominal wall. Using a modified Seldinger technique, a gastrostomy tube is
      placed through the center of the T-bars. METHODS: A retrospective review of all
      PEG tubes placed in pediatric patients from 1997 to 2003 using the T-bar
      gastroscopy "push" technique was conducted. Patients 18 years of age or younger
      were included in the study. Data collected included patient age, operative time,
      procedure location, and complications. RESULTS: The procedure was performed for
      47 children (mean age, 6.4 years), including 15 infants younger than 1 year. The
      indications for long-term enteral access included failure to thrive (n = 11),
      feeding disorder secondary to neurologic dysfunction (n = 31), gastroparesis (n =
      1), and dysphagia (n = 4). The operative time averaged 23 min (range, 12-45 min).
      One major complication occurred (gastrocolonic fistula). The one minor
      complication was early dislodgement of the gastrostomy tube, which required
      replacement. CONCLUSION: This study found the described technique to be safe and
      effective for the placement of gastrostomy tubes in infants and children.

PMID- 17522925
TI  - Comparison of conventional laparoscopic and hand-assisted oncologic segmental
      colonic resection.
AB  - BACKGROUND: Laparoscopically assisted colon resection has evolved to be a viable
      option for the treatment of colorectal cancer. This study evaluates the efficacy
      of hand-assisted laparoscopic surgery (HALS) as compared with totally
      laparoscopic surgery (LAP) for segmental oncologic colon resection with regard to
      lymph node harvest, operative times, intraoperative blood loss, pedicle length,
      incision length, and length of hospital stay in an attempt to help delineate the
      role of each in the treatment of colorectal cancer. METHODS: Patient charts were
      retrospectively reviewed to acquire data for this evaluation. Between June 2001
      and July 2005, 40 patients underwent elective oncologic segmental colon resection
      (22 HALS and 18 LAP). The main outcome measures included lymph node harvest,
      operative times, intraoperative blood loss, pedicle length, incision length, and
      length of hospital stay. RESULTS: The two groups were comparable in terms of
      demographics. The tumor margins were clear in all the patients. The HALS
      resection resulted in a significantly higher lymph node yield than the LAP
      resection (HALS: 16 nodes; range, 5-35 nodes vs LAP: 8 nodes; range, 5-22 nodes;
      p < 0.05) and significantly shorter operative times (HALS: 120 min; range, 78-181
      min vs LAP: 156 min; range, 74-300 min; p < 0.05). Both groups were comparable
      with regard to length of hospital stay, pedicle length, and intraoperative blood
      loss. However, the LAP group yielded a significantly smaller incision for
      specimen extraction (LAP: 7 cm; range, 6-8 cm vs HALS: 5.5 cm; range, 5-7 cm; p <
      0.05). CONCLUSION: The findings suggest that hand-assisted laparoscopic oncologic
      segmental colonic resection is associated with shorter operative times, more
      lymph nodes harvested, and equivalent hospital stays, pedicle lengths, and
      intraoperative blood losses as compared with the totally laparoscopic approach.
      The totally laparoscopic technique was completed with a smaller incision.
      However, this less than 1 cm reduction in incision length has doubtful clinical
      significance.

PMID- 17522926
TI  - Natural orifice surgery with an endoluminal mobile robot.
AB  - Natural orifice transgastric endoscopic surgery promises to eliminate skin
      incisions and reduce postoperative pain and discomfort. Such an approach provides
      a distinct benefit as compared with conventional laparoscopy, in which multiple
      entry incisions are required for tools and camera. Endoscopy currently is the
      only method for performing procedures through the gastrointestinal tract.
      However, this approach is limited by instrumentation and the need to pass the
      entire scope into the patient. In contrast, an untethered miniature robot
      inserted through the mouth would be able to enter the abdominal cavity through a
      gastrotomy for exploration of the entire peritoneal cavity. In this study, the
      authors developed an endoluminal robot capable of transgastric abdominal
      exploration under esophagogastroduodenoscopic (EGD) control. Under EGD control, a
      gastrotomy was created, and the miniature robot was deployed into the abdominal
      cavity under remote control. Ultimately, future procedures will include a family
      of robots working together inside the gastric and abdominal cavities after their
      insertion through the esophagus. Such technology will help to reduce patient
      trauma while providing surgical flexibility.

PMID- 17522927
TI  - Laparoscopic pyloromyotomy is both safe and effective in a district hospital.
AB  - INTRODUCTION: Functional operations of the gastrointestinal tract are ideal
      indications for minimal-access surgery. The aim of this paper was to assess the
      safety and potential benefits of the laparoscopic Ramstedt pyloromyotomy using
      the experience of a single surgeon in a district general hospital. METHODS: 90
      consecutive infants underwent pyloromyotomy: 35 open procedures and 55
      laparoscopic procedures. This is a retrospective study but the operative data of
      the laparoscopic group were collected prospectively. RESULTS: There were no
      differences in demographic data between the groups. The open group had a shorter
      mean operating time, 22.14 min, than the laparoscopic group, 26.04 min (p =
      0.022). There was no significant difference in the time to full feed between the
      two groups (p = 0.076). 62.9% of the infants in the open group vomited compared
      with only 43.4% in the laparoscopic group (p = 0.058). The laparoscopic group had
      shorter postoperative stay, 62.33 hours, compared to 91.89 hours (p = 0.001).
      There was one reoperation in each group: for complete wound dehiscence in the
      open group and for incomplete myotomy in the laparoscopic group. CONCLUSIONS:
      Laparoscopic pyloromyotomy (LPM) is as safe as the open procedure and has the
      potential benefits of shorter hospital stay and improved cosmesis.

PMID- 17522928
TI  - Comparison of three perioperative fluid regimes for laparoscopic donor
      nephrectomy : A prospective randomized dose-finding study.
AB  - BACKGROUND: Pneumoperitoneum (PP), as used for laparoscopic procedures, impairs
      stroke volume, renal blood flow, glomerular filtration rate and urine output.
      This study investigated whether perioperative fluid management can abolish these
      negative effects of PP on hemodynamics. METHODS: Twenty-one patients undergoing
      laparoscopic donor nephrectomy (LDN) were randomized into three groups: group 1
      received overnight infusion and received a bolus of colloid before induction of
      anesthesia, followed by a bolus just before PP; group 2 received overnight
      infusion and a colloid bolus before anesthesia; group 3 served as controls and
      received only infusion during operation. All three groups received the same total
      amount of crystalloids and colloids until nephrectomy. Data analysis of the donor
      included; mean arterial pressure (MAP), stroke volume (SV), left ventricular
      ejection time (LVETc), perioperative urine output and renal function measured as
      the creatinine clearance (CrCl) until one-year post-operative. RESULTS: SV was
      significantly higher in group 1 compared to controls for all measurements. In the
      control group SV significantly decreased after changing from the supine to
      lateral position whereas there was no change in SV in both pre-hydrated groups.
      In all groups, MAP decreased after induction of anesthesia, and restored to pre
      anesthetic values during PP. CrCl decreased in the control group during PP, but
      not in the other groups. From two days postoperative, CrCl was comparable between
      the three study groups. CONCLUSION: Overnight infusion and a bolus of colloid
      just before PP attenuate hemodynamic compromise from PP.

PMID- 17522929
TI  - Evaluation of laparoscopic treatment of common bile duct stones in a prospective
      series of 505 patients: indications and results.
AB  - BACKGROUND: The aim of this prospective study was the evaluation of the
      laparoscopic treatment of common bile duct stones (CBDS) and its indications.
      METHODS: Five hundred five patients who underwent laparoscopic treatment of CBDS
      from October 1990 to September 2006 were included in the prospective study. The
      mean age of the patients was 63 years (range = 19-93). Four hundred fifteen
      patients were classified ASA I and ASA II and 90 were ASA III and ASA IV. CBDS
      were suspected or diagnosed preoperatively in 373 patients (73.8%) and diagnosed
      at intraoperative cholangiography (IOC) in 132 patients (26.2%). A transcystic
      duct extraction (TCDE) was attempted in 254 patients (50.4%) and a primary
      choledochotomy in 251 patients (49.6%). Biliary drainage after choledochotomy was
      used in 148 cases (48.8%). RESULTS: TCDE was successful in 191 cases (75.2%). The
      63 failures were managed by laparoscopic choledochotomy in 53 cases and by
      endoscopic sphincterotomy (ES) in 10 cases. A choledochotomy was thus performed
      in 304 patients and successful in 295 cases (97%). The nine failures were managed
      by six conversions to laparotomy (2%) and three postoperative ES. The overall
      success rate was 96.2%. The morbidity rate was 7.9% with 4.8% of local
      complications and 3.1% of general complications. The mortality rate was 1%. There
      were 14 residual stones (2.8%) that were managed by a second laparoscopy in two
      cases and by ES in 12 cases with four failures managed by laparotomy in one case
      and laparoscopy in three cases. CONCLUSION: Laparoscopic management of CBDS was
      effective in more than 96% of cases and particularly safe in ASA I and ASA II
      patients. It has the advantage over ES followed by laparoscopic cholecystectomy
      (LS) to be a one-stage procedure.

PMID- 17522930
TI  - Is a barium swallow complementary to endoscopy essential in the preoperative
      assessment of laparoscopic antireflux and hiatal hernia surgery?
AB  - BACKGROUND: Barium swallow is considered essential in the preoperative assessment
      of gastroesophaeal reflux disease and hiatal hernias. The objective of this study
      was to investigate the effective value of a barium swallow if complementary to
      the commonly recommended endoscopy before laparoscopic antireflux and hiatal
      hernia surgery. METHODS: We prospectively evaluated 40 consecutive patients who
      were tested with preoperative barium swallow and endoscopy before laparoscopic
      surgery for gastroesophageal reflux disease and/or symptomatic hiatal hernia.
      Results regarding the presence and the type of hiatal hernia found by barium
      swallow and endoscopy were correlated with the intraoperative finding as the
      reference standard. RESULTS: Intraoperative findings revealed 21 axial, 7
      paraesophageal, and 12 mixed hiatal hernias. Barium swallow and endoscopy allowed
      the diagnosis of hiatal hernia in 75% and 97.5%, respectively (p = 0.003). The
      correct classification of hiatal hernia was confirmed in 50% by barium swallow
      and 80% by endoscopy (p = 0.005). CONCLUSIONS: Although barium swallow is
      recommended as an important diagnostic tool in the workup before surgical
      antireflux and hiatal hernia therapy, our results suggest that if mandatory
      endoscopy is performed preoperatively, a barium swallow does not provide any
      further essential information. It seems that barium swallow can be omitted as a
      basic diagnostic test before primary laparoscopic antireflux and hiatal hernia
      surgery.

PMID- 17522931
TI  - A computerized analysis of robotic versus laparoscopic task performance.
AB  - INTRODUCTION: Robotic technology has been postulated to improve performance in
      advanced surgical skills. We utilized a novel computerized assessment system to
      objectively describe the technical enhancement in task performance comparing
      robotic and laparoscopic instrumentation. METHODS AND PROCEDURES: Advanced
      laparoscopic surgeons (2-10 yrs experience) performed three unique task modules
      using laparoscopic and Telerobotic surgical instrumentation (Intuitive Surgical,
      Sunnyvale, CA). Performance was evaluated using a computerized assessment system
      (ProMIS, Dublin, Ireland) and results were recorded as time (s), path (mm) and
      precision. Each surgeon had an initial training session followed by two testing
      sessions for each module. A paired Student's t-test was used to analyze the data.
      RESULTS: Ten surgeons completed the study. 8/10 surgeons had significant
      technical enhancement utilizing robotic technology. CONCLUSIONS: The ProMIS
      computerized assessment system can be modified to objectively obtain task
      performance data with robotic instrumentation. All the tasks were performed
      faster and with more precision using the robotic technology than standard
      laparoscopy.

PMID- 17522932
TI  - Robotically assisted small intestinal strictureplasty in dogs: a survival study
      involving 16 Heineke-Mikulicz strictureplasties.
AB  - BACKGROUND: Robotically assisted surgery offers the advantages of improved
      dexterity and elimination of tremor over conventional laparoscopic surgery. There
      have been few studies to date, however, examining the role of robotics in
      intestinal surgery. This study was undertaken to determine the feasibility and
      safety of using a robotic surgical system in the performance of intracorporeal
      small bowel strictureplasties in dogs. METHODS: Using a robotic surgical system,
      a total of 16 strictureplasties were performed in the small bowel of eight dogs
      (two strictureplasties per dog). Using only intracorporeal robotic surgery, a 2.5
      cm enterotomy was made longitudinally in the small bowel, and then closed in a
      Heineke-Mikulicz configuration with a one-layer running 3-0 braided absorbable
      suture (strictureplasty). All animals were allowed to survive for 7 days with
      prospective monitoring of bowel movements, level of activity, oral intake, and
      abdominal examination. After 7 days, necropsy was performed, examining all
      strictureplasty sites for signs of sepsis. The endpoints of the study were
      recovery of normal intestinal function (bowel movements), intraoperative and
      postoperative complications, and the appearance of the anastomoses at necropsy.
      RESULTS: There was no intraoperative morbidity or mortality. All eight dogs
      survived 7 days and recovered well. All dogs had a bowel movement on the first
      postoperative day, and appeared healthy throughout the study period. Necropsy
      revealed that all 16 strictureplasty sites were healing without signs of sepsis.
      The median time per strictureplasty was 65 min (range, 45-110 min). One dog
      developed a superficial wound infection at a trocar site. CONCLUSIONS: A robotic
      surgical system can successfully be employed in the performance of intestinal
      strictureplasties in dogs. This study supports further investigation into the
      role of robotics in intestinal surgery in humans.

PMID- 17522933
TI  - Upright, supine, or bipositional reflux: patterns of reflux do not affect outcome
      after laparoscopic Nissen fundoplication.
AB  - INTRODUCTION: This study was undertaken to determine if the body position in
      which gastroesophageal reflux occurs before fundoplication--i.e., pattern of
      reflux--affects symptoms before or after laparoscopic Nissen fundoplication.
      METHODS: A total of 417 patients with gastroesophageal reflux disease (GERD)
      underwent pH studies, and the severity of reflux in the upright and supine
      positions was determined. The percent time with pH less than 4 was used to assign
      patients to one of four groups: upright reflux (pH < 4 more than 8.3% of time in
      upright position, n = 80), supine reflux (pH < 4 more than 3.5% of time in supine
      position, n = 73), bipositional reflux (both supine and upright reflux, n = 163),
      or neither (n = 101). Before and after laparoscopic Nissen fundoplication, the
      frequency and severity of symptoms of reflux (e.g., dysphagia, regurgitation,
      choking, heartburn, chest pain) were scored on a Likert scale (0 = never/not
      bothersome to 10 = always/very bothersome). For each patient, symptom scores
      before versus after fundoplication were compared using the Wilcoxon matched pairs
      test; comparisons of symptom scores among patients grouped by reflux patterns
      were made using Kruskal-Wallis test. RESULTS: Before fundoplication, the patterns
      of reflux did not affect the frequency or severity of reflux symptoms. After
      laparoscopic fundoplication, all symptoms of bipositional reflux improved, and
      essentially all symptoms of isolated supine or upright reflux or neither
      improved. CONCLUSIONS: Preoperatively, regardless of the patterns of reflux,
      symptoms among patients were similar. After fundoplication, symptoms of GERD
      improved for all patterns of reflux. Laparoscopic fundoplication imparts dramatic
      and broad relief of symptoms of GERD, regardless of the patterns of reflux.
      Application of laparoscopic Nissen fundoplication is encouraged.

PMID- 17522934
TI  - Postmyotomy recollection of premyotomy symptoms of achalasia is very accurate,
      supporting longitudinal studies of symptom improvement.
AB  - BACKGROUND: Recollection of preoperative symptom frequency and severity may
      change postoperatively, thus invalidating longitudinal studies. This study was
      undertaken to compare symptoms of achalasia before myotomy to patients'
      postoperative recollection of premyotomy symptoms. METHODS: A total of 173
      patients, 54% male, of median age 48 years, have undergone laparoscopic Heller
      myotomy and have been followed through a prospectively maintained registry.
      Preoperatively, patients scored the frequency and severity of their symptoms on a
      Likert scale: 0 (never/very bothersome) to 10 (always/very bothersome).
      Similarly, after laparoscopic Heller myotomy, patients scored the frequency and
      severity of their symptoms, and re-scored their preoperative symptoms. Data are
      presented as median, mean +/- SD. RESULTS: Before myotomy, dysphagia,
      regurgitation, choking, chest pain, vomiting, and heartburn were particularly
      notable; symptom scores nearly globally improved after myotomy (p < 0.05 for all,
      Wilcoxon matched pairs test), especially obstructive symptoms. Postmyotomy
      recollection of premyotomy symptom frequency and severity was neither
      substantively nor consistently different from premyotomy scoring. CONCLUSIONS:
      Before myotomy, patient symptom scores reflected the deleterious impact of
      achalasia. After myotomy, patient symptom scores dramatically improved,
      reflecting the favorable impact of laparoscopic Heller myotomy. Even years after
      myotomy, patient recollection of premyotomy symptom severity and frequency is
      very accurate and supports longitudinal studies of symptom improvement after
      myotomy.

PMID- 17522935
TI  - A novel approach for Roux limb construction via the lesser sac.
AB  - Exposure of the ligament of Treitz for Roux limb construction during laparoscopic
      gastric bypass requires either division or displacement of the omentum. Factors
      compromising this exposure include: (1) a bulky omentum, (2) hepatomegaly, (3)
      adhesions between the omentum and lower abdominal wall or pelvic contents and (4)
      inability to identify the transverse colon because of overlying adipose tissue.
      The lesser sac approach is an alternative method for Roux limb construction
      during laparoscopic gastric bypass when access to the inframesocolic abdomen is
      difficult. In this technique the lesser sac is entered through the gastrocolic
      ligament. The transverse mesocolon is then opened and the ligament of Treitz is
      identified. The jejunum is pulled into the lesser sac and the Roux limb is
      constructed. The jejunojejunostomy is reduced into the inframesocolic
      compartment, the mesenteric defects are closed, and the remaining portion of the
      procedure is completed. This technique provides an alternative method for
      completion of a laparoscopic gastric bypass in patients who would otherwise
      require more extensive surgery.

PMID- 17522936
TI  - Body image, cosmesis, quality of life, and functional outcome of hand-assisted
      laparoscopic versus open restorative proctocolectomy: long-term results of a
      randomized trial.
AB  - BACKGROUND: This study aimed to compare quality of life (QOL), functional
      outcome, body image, and cosmesis after hand-assisted laparoscopic (LRP) versus
      open restorative proctocolectomy (ORP). The potential long-term advantages of LRP
      over ORP remain to be determined. The most likely advantage of LRP is the
      superior cosmetic result. It is, however, unclear whether the size and location
      of incisions affect body image and QOL. METHODS: In a previously conducted
      randomized trial comparing LRP with ORP, 60 patients were prospectively
      evaluated. The primary end points were body image and cosmesis. The secondary end
      points were morbidity, QOL, and functional outcome. A body image questionnaire
      was used to evaluate body image and cosmesis. The Short Form-36 Health Survey and
      the Gastrointestinal Quality of Life Inventory were used to assess QOL. Body
      image and QOL also were assessed preoperatively. RESULTS: A total of 53 patients
      completed the QOL and functional outcome questionnaires. There were no
      differences in functional outcome, morbidity, or QOL between LRP and ORP. At a
      median of 2.7 years after surgery, 46 patients returned the questionnaires
      regarding body image, cosmesis, and morbidity. The body image and cosmesis scores
      of female patients were significantly higher in the LRP group than in the ORP
      group (body image, 17.4 vs 14.9; cosmesis, 19.1 vs 13.0, respectively). The
      female patients in the ORP group had significantly lower body image scores than
      the male patients (14.9 vs 18.3). CONCLUSIONS: This study is the first to show
      that ORP has a negative impact on body image and cosmesis as compared with LRP.
      Functional outcome, QOL, and morbidity are similar for the two approaches. The
      advantages of a long-lasting improved body image and cosmesis for this relatively
      young patient population may compensate for the longer operating times and higher
      costs, particularly for women.

PMID- 17522937
TI  - A new method for intrathoracic anastomosis in laparoscopic esophagectomy.
AB  - The benefits of laparoscopic procedures over the traditional open technique for
      esophagectomy in the management of esophageal cancer are well documented. A
      disadvantage of the laparoscopic technique is longer surgery, particularly in the
      early part of a surgeon's "learning curve." In a two-stage (Ivor-Lewis)
      procedure, performance of the esophagogastric anastomosis within the chest can be
      a "rate-limiting step." A circular stapler is used, which requires placement of a
      purse-string suture or a manually-tied knot around in the transected proximal
      esophagus to secure the anvil in place. This is technically demanding and time
      consuming in the laparoscopic setting. The authors have devised a method that
      obviates the need for a purse string or knot, simplifying the intrathoracic
      esophagogastric anastomosis while still achieving a safe anastomosis.

PMID- 17522938
TI  - The effects of surgical trauma on colorectal liver metastasis.

PMID- 17522939
TI  - Visual working memory influences the performance in virtual image-guided surgical
      intervention.
AB  - BACKGROUND: This study addresses for the first time the relationship between
      working memory and performance measures in image-guided instrument navigation
      with Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR) and GI Mentor
      II (a simulator for gastroendoscopy). In light of recent research on simulator
      training, it is now prime time to ask why in a search for mechanisms rather than
      show repeatedly that conventional curriculum for simulation training has effect.
      METHODS: The participants in this study were 28 Swedish medical students taking
      their course in basic surgery. Visual and verbal working memory span scores were
      assessed by a validated computer program (RoboMemo) and correlated with visual
      spatial ability (MRT-A test), total flow experience (flow scale), mental strain
      (Borg scale), and performance scores in manipulation and diathermy (MD) using
      Procedicus MIST-VR and GI Mentor 11 (exercises 1 and 3). RESULTS: Significant
      Pearson's r correlations were obtained between visual working memory span scores
      for visual data link (a RoboMemo exercise) and movement economy (r = -0.417; p <
      0.05), total time (r = -0.495; p < 0.01), and total score (r = -0.390; p < 0.05)
      using MIST-MD, as well as total time (r = -0.493; p < 0.05) and efficiency of
      screening (r = 0.469; p < 0.05) using GI Mentor 11 (exercise 1). Correlations
      also were found between visual working memory span scores in rotating data link
      (another RoboMemo exercise) and both total time (r = -0.467; p < 0.05) and
      efficiency of screening (r = -0.436; p < 0.05) using GI Mentor 11 (exercise 3).
      Significant Pearson's r correlations also were found between visual-spatial
      ability scores and several performance scores for the MIST and GI Mentor II
      exercises. CONCLUSIONS: Findings for the first time demonstrate that visual
      working memory for surgical novices may be important for performance in virtual
      simulator training with two well-known and validated simulators.

PMID- 17522940
TI  - SEER data: it can be thought provoking, but where do we go from here?

PMID- 17522941
TI  - The negative sestamibi scan: is a minimally invasive parathyroidectomy still
      possible?
AB  - BACKGROUND: Tc-99-sestamibi scanning is utilized to determine whether patients
      with primary hyperparathyroidism (HPT) are candidates for minimally invasive
      parathyroidectomy (MIP). However, if the result of this scan is negative, many
      surgeons recommend bilateral parathyroid exploration because of possible multi
      gland disease. The objectives of this study were to determine whether patients
      with primary HPT and negative sestamibi scans can benefit from additional imaging
      studies and are still potential candidates for MIP. METHODS: Between March 2001
      and April 2006, 578 consecutive patients with HPT underwent parathyroidectomy by
      a single surgeon. Pre-operative sestamibi scans had been done in 458 (79%) of
      these patients, 90 (20%) of which had negative results. These patients formed our
      study cohort. RESULTS: Of the 90 patients, 60 (67%) had a single adenoma, 17
      (19%) double adenomas and 13 (14%) 3- to 4-gland hyperplasias. In 74 (82%)
      patients, localization was further investigated with one or more studies
      including thallium subtraction scans (n = 30), ultrasound (n = 15) and intra
      operative internal jugular venous sampling (n = 49). Additionally, the use of
      radio-guided techniques intra-operatively facilitated minimally invasive
      techniques. Of these 90 patients, 47 had positive results from preoperative
      studies, including 12 positive thallium, 5 positive ultrasound and 13 positive
      internal jugular sampling results. In addition, positive results were observed
      for 17 patients using radio-probe techniques in the operating room. Accordingly,
      minimally invasive techniques were attempted in these 47 patients; 42 (89%) had
      single adenomas and in 5 the technique was converted to bilateral exploration for
      double adenoma/hyperplasia. In the setting of a negative sestamibi, the
      sensitivities of thallium scans and ultrasound were 30% and 27%, respectively.
      The overall cure rate in the 90 patients with negative sestamibi scans was 99%.
      CONCLUSION: In patients with primary HPT and a negative sestamibi scan, most
      patients (67%) will have a single adenoma. These patients benefitted from
      additional localization tests, which yielded a positive result in 52% of
      patients. Therefore, even in the setting of a negative sestamibi scan, the
      majority of patients with primary HPT are still candidates for MIP.

PMID- 17522942
TI  - An analysis of resection vs transplantation for early hepatocellular carcinoma:
      defining the optimal therapy at a single institution.
AB  - BACKGROUND: The reported survival after liver transplantation (OLT) for early
      hepatocellular carcinoma (HCC) is superior to the results of liver resection
      (LR), but few analyses have considered long waiting times and patient drop-offs
      due to tumor progression. METHODS: From 1995-2005, 347 patients with HCC were
      evaluated at our institution and underwent either LR (n = 174) or placed on the
      OLT waiting list (n = 173). Patients who only underwent ablation were not
      included. After eliminating patients with 1) incidental tumors after OLT, 2)
      tumors outside of Milan criteria, 3) preoperative vascular invasion prior to LR
      and 4) Child-Pugh Class C cirrhosis prior to OLT, 261 patients (LR = 121; OLT =
      140) were included in this analysis. RESULTS: Median follow-up time was 35
      months. Median waiting time for OLT was 7.7 months; during this time, 30 patients
      were taken off the waiting list. Overall survival (OS) from time of listing or LR
      was not different between the two groups; 1, 3, and 5 year OS after LR was 89%,
      75%, and 56% compared with 90%, 70%, and 64% for OLT (P = .84). Only patients who
      waited <4 months for OLT (n = 67) had better survival than those who underwent LR
      (P = .05). Patients who waited longer that four months for OLT had a 2.5x higher
      risk of death in a Cox multivariate model [odds ratio (OR) 2.5; 95% confidence
      interval (CI): 1.3-5; P = .007]. CONCLUSION: Unless waiting time is short (< 4
      months), the survival of patients with early HCC is similar between LR and LT.

PMID- 17522943
TI  - Comparing surgical outcomes in obese women undergoing laparotomy, laparoscopy, or
      laparotomy with panniculectomy for the staging of uterine malignancy.
AB  - BACKGROUND: Limiting surgical morbidity while maintaining staging adequacy is a
      primary concern in obese patients with uterine malignancy. The goal of this study
      was to compare the surgical adequacy and postoperative morbidity of three
      surgical approaches to staging the disease of obese women with uterine cancer.
      METHODS: The records of all patients with a body mass index (BMI) of >or=35
      undergoing primary surgery for uterine corpus cancer at our institution from
      January 1993 to May 2006 were reviewed. Patients were assigned to three groups on
      the basis of planned surgical approach-standard laparotomy, laparoscopy, or
      laparotomy with panniculectomy. Standard statistical tests appropriate to group
      size were used to compare the three groups. RESULTS: In all, 206 patients with a
      BMI of >or=35 were grouped as follows: laparotomy, 154 patients; laparoscopy, 25
      patients; and laparotomy with panniculectomy, 27 patients. Median BMI was 41
      (range, 35-84). Regional lymph nodes were removed in 45% of the laparotomy
      patients, 40% of the laparoscopy patients, and 70% of the panniculectomy patients
      (P = .04). Compared with laparotomy, both laparoscopy and panniculectomy yielded
      higher median pelvic and total lymph node counts (P = .001). Operative time was
      shortest after standard laparotomy, and blood loss was greatest after
      panniculectomy. The incidence of all incisional complications was lower for
      panniculectomy (11%) and laparoscopy (8%) compared with standard laparotomy (35%)
      (P = .002). On multivariate analysis, a significantly lower risk of total
      incisional complications was seen for patients undergoing panniculectomy (risk
      ratio, .25; 95% confidence interval, .071-.88) and laparoscopy (risk ratio, .19;
      95% confidence interval, .04-.94). CONCLUSIONS: Both laparoscopic staging and
      panniculectomy in a standardized fashion were associated with an improved lymph
      node count and a lower rate of incisional complications than laparotomy alone.
      Although definitive conclusions are limited by low patient numbers, the
      substantial decrease in wound complications suggests that these two approaches
      should be considered for obese patients undergoing uterine cancer staging.

PMID- 17522944
TI  - Surgical removal of the primary tumor increases overall survival in patients with
      metastatic breast cancer: analysis of the 1988-2003 SEER data.
AB  - BACKGROUND: Primary treatments for stage IV breast cancer are chemotherapy and
      radiation, with surgery usually reserved for tumor-related complications. We
      sought to determine whether surgical removal of the primary tumor provides a
      survival advantage for women with metastatic breast cancer. METHODS: We conducted
      a retrospective, population-based cohort study by using the 1988-2003
      Surveillance, Epidemiology, and End Results (SEER) program data. By use of
      multivariate Cox regression models, overall survival in women with stage IV
      disease was compared between women who underwent surgical excision of their
      breast tumor with women who did not, controlling for potential confounding
      demographic, tumor- and treatment-related variables, and propensity scores
      (accounting for variables associated with the likelihood of having surgery).
      RESULTS: Of 9734 SEER patients with stage IV breast cancer, 47% underwent breast
      cancer surgery and 53% did not. Median survival was longer for women who had
      surgery than for women who did not, both among women who were alive at the end of
      the study period (36.00 vs. 21.00 months; P < .001) and among women who had died
      during follow-up (18.00 vs. 7.00 months; P < .001). After controlling for
      potential confounding variables and propensity scores, patients who underwent
      surgery were less likely to die during the study period compared with women who
      did not undergo surgery (adjusted hazard ratio, .63, 95% confidence interval, .60
      .66). CONCLUSIONS: Analysis of the 1988-2003 SEER data indicated that extirpation
      of the primary breast tumor in patients with stage IV disease was associated with
      a marked reduction in risk of dying after controlling for variables associated
      with survival.

PMID- 17522945
TI  - The impact of postoperative complications on long-term outcomes following
      curative resection for colorectal cancer.
AB  - BACKGROUND: This study aimed to investigate the impact of postoperative
      complications on long-term survival and disease recurrence in patients who
      underwent curative resection for colorectal cancer. METHOD: Patients who
      underwent radical resection for colorectal cancer with curative intent from
      January 1996 to December 2004 were included. Operative mortality and morbidity
      were documented prospectively. Factors that might affect long-term outcome were
      analyzed with multivariate analysis. RESULTS: Curative resection was performed in
      1657 patients (943 men), and the median age was 70 years (range: 24-94 years).
      The 30-day mortality was 2.4%, and the complication rate was 27.3%. Age over 70
      years (P < .001, odds ratio: 2.06, 95% CI: 1.63-2.61), male gender (P = .001,
      odds ratio: 1.49, 95% CI: 1.19-1.88), emergency operation (P < .001, odds ratio:
      3.14, 95% CI: 2.26-4.35) and rectal cancer (P < .001, odds ratio: 1.41, 95% CI:
      1.25-1.61) were associated with a significantly higher complication rate. With
      exclusion of patients who died within 30 days, the median follow-up of the
      surviving patients was 45.3 months. The 5-year overall survival was 64.9%, and
      the overall recurrence rate was 29.1%. The presence of postoperative
      complications was an independent factor associated with a worse overall survival
      (P = .023, hazard ratio: 1.26; 95% CI: 1.03-1.52) and a higher overall recurrence
      rate (P = .04, hazard ratio: 1.26; 95% CI: 1.01-1.57). CONCLUSION: The presence
      of postoperative complication not only affects the short-term results of
      resection of colorectal cancer, but the long-term oncologic outcomes are also
      adversely affected. Long-term outcomes can be improved with efforts to reduce
      postoperative complications.

PMID- 17522946
TI  - Preoperative lymphoscintigraphy predicts the successful identification but is not
      necessary in sentinel lymph nodes biopsy in breast cancer.
AB  - BACKGROUND: Although preoperative lymphoscintigraphy in sentinel lymph node
      biopsy (SLNB) for breast cancer patients is undergone commonly, its clinical
      significance remains controversial. METHODS: We retrospectively analyzed our
      database that contained 636 consecutive breast cancer patients who received
      preoperative lymphoscintigraphy before SLNB. RESULTS: The sentinel lymph nodes
      (SLNs) of 86.5% of patients were well imaged by lymphoscintigraphy, and SLN were
      located extra-axilla in 5.3% patients. The visualization of SLN in
      lymphoscintigraphy was not associated with histopathologic type, location, and
      stage of primary tumor, as well as the time interval from injection of
      radiocolloid to surgery. The negative lymphoscintigraphy results were associated
      with excision ;biopsy before injection of radiocolloid and positive axillary node
      statues. The SLN was successfully detected in 625 (98.3%) enrolled patients.
      Failure of surgical identification of axillary SLN was associated with whether
      hot spot was imaged by lymphoscintigraphy. However, we identified axillary SLN in
      90 (90.9%) out of 99 patients with negative axillary findings in
      lymphoscintigram. The false negative rate of SLNB in our study was 16.0% (15 of
      94) among patients of training group, and there was no significant difference in
      the false negative rate between patients who had axillary hot spot in
      lymphoscintigram and those who had not (P = .273). CONCLUSIONS: Visualization of
      SLN in preoperative lymphoscintigraphy predicted the successful SLN
      identification. However, it was less informative for the location of SLN during
      operation. Considering the complexity, time consumed, and cost,
      lymphoscintigraphy should at present be undergone for investigation purposes
      only.

PMID- 17522947
TI  - Percutaneous radiofrequency ablation for recurrent hepatocellular carcinoma after
      hepatectomy: long-term results and prognostic factors.
AB  - BACKGROUND: We evaluated the long-term survival results and safety of
      percutaneous radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma
      (HCC) after hepatectomy, and assessed the prognostic factors that can influence
      its long-term therapeutic results. METHODS: One hundred and two patients, who had
      119 recurrent HCC in their livers, underwent ultrasound-guided percutaneous RFA.
      All the patients had a history of hepatic resection as a first-line treatment
      modality for HCC. The mean diameter of the recurrent tumors was 2.0 cm (range,
      0.8-5.0 cm). We evaluated the effectiveness rates, local tumor progression rates,
      survival rates, and complications. We also assessed the prognostic factors of the
      survival rates by using Cox proportional hazard models. RESULTS: The primary
      effectiveness rate was 93.3% (111 of 119). The cumulative rates of local tumor
      progression at 1, 3, and 5 years were 6.0, 8.6, and 11.9%, respectively. The
      cumulative survival rates at 1, 2, 3, 4, and 5 years were 93.9, 83.7, 65.7, 56.6,
      and 51.6%, respectively. Patients with a lower serum alpha-fetoprotein (AFP)
      level (<or=100 microg/L) before RFA or with small resected tumors (<or=5 cm)
      demonstrated better survival results (P < .05). There was only one major
      complication (liver abscess, 1.0% per treatment) during the follow-up period.
      There were no procedure-related deaths. CONCLUSIONS: Percutaneous RFA is an
      effective and safe treatment modality for intrahepatic recurrent HCC after
      hepatectomy. Serum AFP level before RFA and resected tumor size were significant
      prognostic predictors of long-term survival.

PMID- 17522948
TI  - Burden and control of musculoskeletal conditions in developing countries: a joint
      WHO/ILAR/BJD meeting report.

PMID- 17522949
TI  - The role of malignancies in patients with catastrophic anti-phospholipid
      (Asherson's) syndrome.
AB  - The catastrophic anti-phospholipid syndrome (CAPS) differs from the anti
      phospholipid syndrome in its accelerated systemic involvement leading to multi
      organic failure. In this study, the occurrence of malignancies in patients with
      CAPS was evaluated and the clinical findings of CAPS patients with and without
      malignancies were compared. We investigated the web site-based international
      registry of patients with CAPS for all cases in which both CAPS and underlying
      malignancies were present. The clinical characteristics of these cases were
      subsequently evaluated to establish common characteristics. The CAPS registry
      included information on a total of 262 cases. Twenty-three (9%) patients suffered
      from malignancies. In 78% of these patients, the malignancy itself or the
      treatment modalities instituted for the carcinoma was the precipitating factor of
      CAPS. Only 39% of CAPS patients with malignancies recovered in comparison to 58%
      of patients without malignancies (p = 0.07). Treatment modalities, however, did
      not differ significantly between these patients. Infections were not evident as
      precipitating factors for any of the malignancy patients. The mean age of
      patients with malignancies was 9 years older than the average age of other
      patients with CAPS and the prevalence of SLE was significantly less common than
      in patients without malignancy. Malignancy may play a pathogenic role in patients
      with CAPS, whereas infections are more important as triggering factors in
      patients without malignancies. CAPS patients with malignancies are generally
      older than CAPS patients without malignancies; they generally have the worst
      prognosis of the entire CAPS cohort.

PMID- 17522950
TI  - A follow-up study of minimally invasive lip biopsy in the diagnosis of Sjogren's
      syndrome.
AB  - The aims of this study were to characterize a minimally invasive technique of
      minor salivary gland biopsy of the lower lip and to present a large patient
      material undergoing this procedure because of a suspicion of Sjogren's syndrome
      (SS), as well as to assess the procedure's short-term and long-term value as a
      diagnostic test and a prognostic factor. The sample consists of consecutive 191
      patients undergoing lower lip biopsy in 1987-1990 in Kanta-Hame Central Hospital,
      Hameenlinna, Finland. The method used was the retrospective chart review. Only
      three (1.6%) of the biopsies were uninformative, and only one (0.5%) of the
      patients had a biopsy complication. In 41% of the cases, biopsy was suggestive of
      SS. Females and elderly patients were more likely to have a positive biopsy
      result. Surprisingly, a large diversity between pathologists was observed. With
      the use of focus score instead of older Chisholm classification as an indicator
      of SS, the specificity of SS diagnostics improved, and the variability between
      pathologists diminished. Neither SS diagnosis nor positive lip biopsy for SS
      predicted patients' long-term outcome. In only three patients (1.6%) did the
      histological diagnosis change due to repeated biopsies. The minimal invasive
      lower lip biopsy technique presented in this study is a reliable and safe aid in
      SS diagnostics. The currently recommended histological grading system (focus
      score > or = 1 suggesting SS) is more specific and reproducible than older
      Chisholm classification. Repeated biopsy very rarely adds new information.

PMID- 17522951
TI  - Pulsed photothermal temperature profiling of agar tissue phantoms.
AB  - We determine experimentally the accuracy of pulsed photothermal radiometric
      (PPTR) temperature depth profiling in water-based samples. We use custom tissue
      phantoms composed of agar gel layers separated by very thin absorbing layers. Two
      configurations of the acquisition system are compared, one using the customary
      spectral band of the InSb radiation detector (3.0-5.5 microm) and the other with
      a spectrally narrowed acquisition band (4.5-5.5 microm). The laser-induced
      temperature depth profiles are reconstructed from measured radiometric signals
      using a custom minimization algorithm. The results correlate very well with
      phantom geometry as determined by optical coherence tomography (OCT) and
      histology in all evaluated samples. Determination of the absorbing layer depth
      shows good repeatability with spatial resolution decreasing with depth. Spectral
      filtering improves the accuracy and resolution, especially for shallow absorption
      layers (~120 microm) and more complex structures (e.g., with two absorbing
      layers). The average full width at half maximum (FWHM) of the temperature peaks
      equals 23% of the layer depth.

PMID- 17522952
TI  - Analysis of rice genes induced by striped stemborer (Chilo suppressalis) attack
      identified a promoter fragment highly specifically responsive to insect feeding.
AB  - The objective of this study was to identify rice gene promoters that are
      specifically induced by feeding of the striped stemborer (Chilo suppressalis).
      Two PCR-selected cDNA subtractive libraries were constructed from the rice
      variety Minghui 63. Up- and down-regulated cDNAs induced by C. suppressalis
      feeding were arrayed on nylon membranes. After array hybridization and Northern
      blot analysis, a cDNA (B1-A04) encoding a putative subtilisin/chymotrypsin
      inhibitor was found to be rapidly and highly induced by C. suppressalis feeding,
      compared with mechanical wounding. The putative promoter region, spanning from 
      1,569 to +446 relative to the transcriptional initiation site was isolated, fused
      to the GUS gene (beta-glucuronidase reporter gene) and introduced by
      Agrobacterium-mediated transformation to rice. In non-infested plants, the GUS
      activity driven by this promoter fragment was detected in culms and panicles, but
      not in leaves and sheaths. At 6 h after insect feeding, GUS activity was
      significantly induced in sheaths and culms, but not in leaves. GUS activity and
      native B1-A04 gene were not induced by JA and ABA treatment. A serial deletion
      analysis revealed two regions (-1,569 to -1,166 and -1,166 to -582) that
      negatively regulate the gene expression in sheaths of non-infested plants but not
      in insect-infested plants. An electrophoretic mobility shift assay (EMSA)
      identified 7 DNA fragments with various binding activities with nuclear proteins
      from mechanically wounded, insect-infested and untreated plants, and their
      possible roles in gene regulation were speculated. This promoter fragment should
      have utility in development of insect resistant transgenic crops.

PMID- 17522953
TI  - Transgenic Arabidopsis and tobacco plants overexpressing an aquaporin respond
      differently to various abiotic stresses.
AB  - Despite the high isoform multiplicity of aquaporins in plants, with 35 homologues
      including 13 plasma membrane intrinsic proteins (PIPs) in Arabidosis thaliana,
      the individual and integrated functions of aquaporins under various physiological
      conditions remain unclear. To better understand aquaporin functions in plants
      under various stress conditions, we examined transgenic Arabidopsis and tobacco
      plants that constitutively overexpress Arabidopsis PIP1;4 or PIP2;5 under various
      abiotic stress conditions. No significant differences in growth rates and water
      transport were found between the transgenic and wild-type plants when grown under
      favorable growth conditions. The transgenic plants overexpressing PIP1;4 or
      PIP2;5 displayed a rapid water loss under dehydration stress, which resulted in
      retarded germination and seedling growth under drought stress. In contrast, the
      transgenic plants overexpressing PIP1;4 or PIP2;5 showed enhanced water flow and
      facilitated germination under cold stress. The expression of several PIPs was
      noticeably affected by the overexpression of PIP1;4 or PIP2;5 in Arabidopsis
      under dehydration stress, suggesting that the expression of one aquaporin isoform
      influences the expression levels of other aquaporins under stress conditions.
      Taken together, our results demonstrate that overexpression of an aquaporin
      affects the expression of endogenous aquaporin genes and thereby impacts on seed
      germination, seedling growth, and stress responses of the plants under various
      stress conditions.

PMID- 17522954
TI  - Biochemical properties of a plastidial DNA polymerase of rice.
AB  - Plastids are organelles unique to plant cells and are responsible for
      photosynthesis and other metabolic functions. Despite their important cellular
      roles, relatively little is known about the mechanism of plastidial DNA
      replication and repair. Recently, we identified a novel DNA polymerase in Oryza
      Sativa L. (OsPOLP1, formerly termed OsPolI-like) that is homologous to
      prokaryotic DNA polymerase Is (PolIs), and suggested that this polymerase might
      be involved in plastidial DNA replication and repair. Here, we propose to rename
      the plant PolI homologs as DNA polymerase pi (POLP), and investigate the
      biochemical properties of full-length OsPOLP1. The purified OsPOLP1 elongated
      both DNA and RNA primer hybridized to a DNA template, and possessed a 3'
      exonuclease activity. Moreover, OsPOLP1 displayed high processivity and fidelity,
      indicating that this polymerase has the biochemical characteristics appropriate
      for DNA replication. We found that POLPs have two extra sequences in the
      polymerase domain that are absent in prokaryotic PolIs. Deletion of either insert
      from OsPOLP1 caused a decrease in DNA synthetic activity, processivity, and DNA
      binding activity. In addition, OsPOLP1 efficiently catalyzed strand displacement
      on nicked DNA with a 5'-deoxyribose phosphate, suggesting that this enzyme might
      be involved in a repair pathway similar to long-patch base excision repair. These
      results provide insights into the possible role of POLPs in plastidial DNA
      replication and repair.

PMID- 17522955
TI  - A collection of 10,096 indica rice full-length cDNAs reveals highly expressed
      sequence divergence between Oryza sativa indica and japonica subspecies.
AB  - Relatively few indica rice full-length cDNAs were available to aid in the
      annotation of rice genes. The data presented here described the sequencing and
      analysis of 10,096 full-length cDNAs from Oryza sativa subspecies indica
      Guangluai 4. Of them, 9,029 matched rice genomic sequences in publicly-available
      databases, and 1,200 were identified as new rice genes. Comparison with the
      knowledge-based Oryza Molecular Biological Encyclopedia japonica cDNA collection
      indicated that 3,316 (41.6%) of the 7,965 indica-japonica cDNA pairs showed no
      distinct variations at protein level (2,117 indica-japonica cDNA pairs showed
      fully identical and 1,199 indica-japonica cDNA pairs showed no frame shift).
      Moreover, 3,645 (45.8%) of the indica-japonica pairs showed substantial
      differences at the protein level due to single nucleotide polymorphisms (SNPs),
      insertions or deletions, and sequence-segment variations between indica and
      japonica subspecies. Further experimental verifications using PCR screening and
      quantitative reverse transcriptional PCR revealed unique transcripts for indica
      subspecies. Comparative analysis also showed that most of rice genes were evolved
      under purifying selection. These variations might distinguish the phenotypic
      changes of the two cultivated rice subspecies indica and japonica. Analysis of
      these cDNAs extends known rice genes and identifies new ones in rice.

PMID- 17522956
TI  - Non-omnia moriantur-toxicity of mancozeb on dead wood microarthropod fauna.
AB  - The effect of Dithane M-45 (dithiocarbamate fungicide; active substance:
      mancozeb) was studied on microarthropod fauna inhabiting dead wood. Although the
      exposure was almost never 100% lethal for the majority of observed taxa, almost
      all (Mesostigmata, Oribatida, some Uropodina, Actinedida, Collembola and
      Diplopoda) showed very high correlation between concentration of the fungicide
      and mortality (r > 0.86). Only Stigmaeidae showed low correlation (r = 0.293).
      For the majority of taxa LC(50 )values were close to the concentrations used
      during agrochemical activities in woods. Only Trachytes aegrota showed full
      susceptibility to the fungicide within the range of recommended field
      concentrations used in forestry (characterised by the low LC(95 )value).
      Tolerance of mesostigmatid and oribatid mites was found to differ between
      juveniles and adults, but not consistently. Related Uropodina species varied in
      susceptibility to the fungicide.

PMID- 17522957
TI  - Eradication of cross-contaminated cell lines: a call for action.
AB  - This "white paper" was prepared and widely disseminated in an attempt to sound an
      alarm about the long-term existence of a grave, unresolved and growing problem
      that affects a significant portion of biomedical research, namely, the use of
      misidentified and cross-contaminated cell cultures. The "white paper" shows how
      bold action could bring about a profession-wide change in practice that would
      prevent further erosion. Misidentification and inter- and intra-specific cross
      contamination of mammalian cell cultures used in research continues as a
      widespread problem despite an awareness that dates back more than 45 years.
      Awareness of the problem has led to a good understanding of the causes of cross
      contamination and appropriate preventive measures. It has also led to the
      application of robust methods for the authentication of cell lines. Yet the
      problem continues unabated. Estimates of the incidence of research papers flawed
      by the use of misidentified and cross-contaminated cell cultures approximate 15
      20%. The gravity of the situation calls for a strategy that would deliver a
      remedial message of authentication to virtually all cell culture researchers and
      also ensure compliance with the message. At the core of the strategy proposed
      herein is having cell line authentication as a condition for the award of
      research grants and for the publication of research findings.

PMID- 17522958
TI  - Effect of O-superfamily conotoxin SO3 on synchronized spontaneous calcium spikes
      in cultured hippocampal networks.
AB  - SO3 belongs to the O-superfamily of conotoxins and is known to have analgesic
      effects in experimental animals. In order to explore the mechanism of its
      potential pharmacological actions, the effect of SO3 on synchronized spontaneous
      calcium spikes was examined in cultured hippocampal networks by calcium imaging.
      Spontaneous oscillations of intracellular concentrations of calcium (Ca(2+)) in
      the form of waves and spikes are found in cultured hippocampal networks. Exposure
      to increasing concentrations of SO3 resulted in a progressive decrease in
      synchronized spontaneous calcium spikes. The higher concentrations (0.1
      micromol/L and 1 micromol/L) of SO3 showed the strongest inhibition. The rank
      order of inhibition was 1 micromol/L > 0.1 micromol/L > 10 micromol/L > 0.01
      micromol/L. This action of SO3 in reducing synchronized calcium spikes suggests a
      possible application for therapeutic treatment of epilepsy.

PMID- 17522959
TI  - A note on the paper entitled "JEDA: joint entropy diversity analysis. An
      information-theoretic method for choosing diverse and representative subsets from
      combinatorial libraries" [Melissa R. Landon, Scott E. Schaus, Molecular Diversity
      (2006) 10 333-339].
AB  - Recently, Landon and Schaus [1] published a very interesting article providing an
      algorithm that allows the selection of a representative subset taken form a
      molecular library. The aim of this note is to argue that some aspects discussed
      in the article remain unclear despite it having passed a review process. That is
      because the manuscript check was not complete and, possibly, it was published
      prematurely. There are several concepts that are not well defined or explained in
      the text. This note will attempt to focus on some of those points, transmitting
      them to the reader with the hope that a door is being opened to a more complete
      discussion and understanding of the article. At the same time, this is a good
      opportunity to recall the relevance of this new and promising method.

PMID- 17522960
TI  - Effects of oral tetrachlorvinphos fly control (Equitrol) administration in
      horses: physiological and behavioural findings.
AB  - Highly reactive horses may pose risks to humans involved in equestrian
      activities. Among the factors that may affect horses' reactivity to external
      stimuli are pesticides used for fly control in equine facilities. The
      organophosphorus (OP) insecticide tetrachlorvinphos (TCVP) is used as a feed
      through larvicide to prevent completion of the fly larval life cycle in horse
      manure. TCVP exerts its effect by inhibiting the enzyme cholinesterase (ChE)
      leading to the accumulation of the neurotransmitter acetylcholine (AChE) in
      synapses of the central and peripheral nervous systems. The aim of the present
      study was to investigate alterations of whole-blood ChE levels associated with
      feeding a commercially available product (Equitrol, Farnam Companies, Inc.) to
      horses for fly control. A second aim was to report neurological, physiological
      and behavioural findings in addition to profiles of selected immune markers (IFN
      gamma, IL-12p40 and COX-2) and serum thyroid hormones during and after a 30-day
      treatment period of TCVP feeding. The results indicated significant decreases in
      whole-blood ChE activity and concomitant behavioural alterations, manifested as
      increased reactivity and decreased controllability in treated horses. No changes
      were detected in physiological or neurological parameters, immune markers or
      thyroid hormones in treated (n=6) or control (n=4) horses during the course of
      the study.

PMID- 17522961
TI  - Quality of life in the elderly patients on dialysis.
AB  - The pattern of end-stage renal disease (ESRD) has changed significantly with the
      emerging predominance of elderly patients. Age is no longer seen as a
      contraindication to dialysis. Based on 2004 data, in the USA, patients aged 45-64
      years old comprise the largest portion of the incident population, while patients
      aged 75 and older have the highest incident rates of ESRD. Mortality is higher
      among the elderly dialysis patients for whom cardiovascular diseases and
      infections are the most common causes of death. The quality of life (QoL) of
      these patients has been found to vary in different investigations, dependent on
      such factors as the investigator(s), the composition of the study group and the
      criteria used, among others; however, age was always found one of the major
      determinants of their QoL. Quality-of-life data suggest that older dialysis
      patients have similar levels of social functioning and mental health as younger
      dialysis patients but that their level of physical functioning is poorer. As
      such, the survival and QoL of elderly patients depends mainly on the severity of
      the comorbid conditions. The rationing of dialysis on the basis of age alone is
      not justified as dialysis can provide elderly patients with the means to gain the
      health status that permits them to enjoy life, but in their own way.

PMID- 17522962
TI  - Biomedical evaluation of polyvinyl alcohol-gelatin esterified hydrogel for wound
      dressing.
AB  - The wound is a biosynthetic environment in which numerous cellular processes are
      interlinked in the process of repair. Modern dressings are designed to facilitate
      wound healing rather than just to cover it. Hydrogel dressing can protect injured
      skin and keep it appropriately moist to speed the healing process by absorbing
      exudates while maintaining the products of tissue repair, including growth factor
      and lysosomes, in contact with the wound. The design and development of novel
      membrane of hydrogels prepared by esterification of polyvinyl alcohol with
      gelatin were attempted. Contact angle of goat blood was determined. The hydrogel
      was characterized by hemolysis test and water vapor transmission rate. Diffusion
      coefficient of salicylic acid (SA) and gatifloxacin, a fourth generation
      fluoroquinolone, through the membrane was determined. Both the drugs were used as
      model drug. Methyl tetrazolium dye assay of the membrane was done using L929
      fibroblast cell line and mice splenocytes to establish the biocompatibility of
      the membrane. The equilibrium goat blood-in-air contact angles of measured ester
      films ranged from 56 to 60 degrees . The hydrogel was found to be hemocompatible
      and moisture retentive indicating its possible use in moist wound care. The
      diffusion coefficient of SA and gatifloxacin through the membrane was found to be
      1.49 x 10(-5) and 3.97 x 10(-6) cm(2)/s respectively. The membrane was found to
      be compatible with the L929 fibroblast cell line and mice splenocytes.

PMID- 17522963
TI  - An improved method for the measurement of mechanical properties of bone by
      nanoindentation.
AB  - Nanoindentation is widely used to measure the mechanical properties of bio
      tissues. However, viscoelastic effects during the nanoindentation are seldom
      considered rigorously, although they are in general very significant in bio
      tissues. In this study, a recently developed method for correcting the
      viscoelastic effects during nanoindentation is applied to mice bone samples. This
      method is found to yield reliable elastic modulus and hardness results from
      forelimb and femur cortical bone samples of C57 BL/6N and ICR mice. The creep
      properties of the samples are also characterized by a novel procedure using
      nanoindentation. The measured mechanical properties correlate well with the
      calcium content of the bone samples.

PMID- 17522964
TI  - Poly(acrylic acid) modified calcium phosphate cements: the effect of the
      composition of the cement powder and of the molecular weight and concentration of
      the polymeric acid.
AB  - Polymer modified calcium phosphate cements made with cement powders of varying
      tetracalcium phosphate [TTCP] content were prepared using two different molecular
      weight fractions of poly(acrylic acid) at four different concentrations. The
      ratio of the precursors (TTCP:DCPA) in the cement powder was found to influence
      the initial setting which decreased with increasing concentration of TTCP in the
      powder phase. It was also observed that cements derived from the higher molecular
      weight containing PAA yielded significantly (P < 0.05) shorter initial setting
      time (Ti) than cements containing the lower molecular weight, poly(acrylic acid)
      [GE7 PAA] The effect of the varying the TTCP content in the three different
      cement types PCPC-A, PCPC-B and PCPC-C showed that the trends of the compressive
      strength were specific to the concentration and molecular weight of the poly
      (acrylic acid). A 20% concentration of Glascol-E7 with a cement powder composed
      of an equimolar ratio of precursors (PCPC-B) resulted in optimal compressive
      strength within the range investigated. The TTCP content of the cement powder
      could also be varied to improve the diametral tensile strengths of the cements;
      the specific effects however, were again governed by both the concentration and
      molecular weight of the constituent poly (acrylic acid). The influence of TTCP on
      both the initial setting time and diametral tensile strength was related to the
      Ca (2+) ion concentration, which determined the rate and amount of cross-linking
      in the cement.

PMID- 17522965
TI  - Comparative phloem chemistry of Manchurian (Fraxinus mandshurica) and two North
      American ash species (Fraxinus americana and Fraxinus pennsylvanica).
AB  - Recent studies have investigated interspecific variation in resistance of ash
      (Fraxinus spp.) to the exotic wood-boring beetle, emerald ash borer (EAB, Agrilus
      planipennis). Manchurian ash (Fraxinus mandshurica) is an Asian species that has
      coevolved with EAB. It experiences little EAB-induced mortality compared to North
      American ashes. Host phloem chemistry, both constitutive and induced, might
      partly explain this interspecific variation in resistance. We analyzed the
      constitutive phloem chemistry of three ash species: Manchurian ash and North
      American white (Fraxinus americana) and green (Fraxinus pennsylvanica) ash.
      Analysis of the crude phloem extracts revealed the presence of an array of
      phenolic compounds including hydroxycoumarins, a monolignol, lignans,
      phenylethanoids, and secoiridoids. Both qualitative and quantitative differences
      were observed among the three ash species. Hydroxycoumarins and the
      phenylethanoids, calceloariosides A and B, were present only in the phloem of
      Manchurian ash and might represent a mechanism of resistance against EAB.

PMID- 17522966
TI  - Solvent and pH effects on the fluorescence of 7-(dimethylamino)-2
      fluorenesulfonate.
AB  - A novel water-soluble solvatochromic molecule, 7-(dimethylamino)-2
      fluorenesulfonate (2,7-DAFS), was prepared by a three-step reaction from 2
      nitrofluorene in good overall yield. The pH and solvent effects on the UV-VIS
      absorption and fluorescence spectra of 2,7-DAFS have been studied. Protonation of
      the dimethylamino group switches the absorption from intramolecular charge
      transfer (ICT) to pi --> pi* transition. The ground state pKa value of 2,7-DAFS
      was determined as 4.51. The fluorescence spectrum of the excited basic form,
      *(DAFS), shows a structureless single band with a large Stokes shift, whereas
      that of the acidic form, *((+)HDAFS), exhibits a structured band with a small
      Stokes shift. The emission intensities of the basic and acidic forms versus pH/Ho
      plots show stretched sigmoidal curves and indicate that (1) the rate of
      deprotonation of *((+)HDAFS) is comparable to the fluorescence decay of the
      species, and (2) the efficient proton-induced quenching of *(DAFS) fluorescence
      occurs. The pKa* was estimated as -1.7 from the fluorescence titration curve. The
      fluorescence maximum of *(DAFS) is blue-shifted as the polarity of solvent
      decreases. However, no clear dependency of the emission intensity and spectral
      half width, and thus fluorescence quantum yield, on the solvent polarity was
      revealed. It appears that the fluorescence sensitivity of 2,7-DAFS is 15
      approximately 25 times greater than the sensitivity of a widely utilized
      fluorescent probe, 5-(dimethylamino)-1-naphthalenesulfonate. This higher
      sensitivity, together with the ease of derivatization, would provide the fluorene
      based fluorescent molecules significant advantages for a variety of applications.

PMID- 17522967
TI  - Kinetics of p-nitrophenyl acetate hydrolysis catalyzed by Mucor javanicus lipase
      in AOT reverse micellar solutions formulated in different organic solvents.
AB  - The rate of hydrolysis of p-nitrophenyl acetate (PNPA) catalyzed by Mucor
      javanicus lipase has been measured in AOT reverse micellar solutions formulated
      in aliphatic hydrocarbons, aromatic hydrocarbons and a chlorinated compound. The
      study has been performed at a single value of W=([water]/[AOT])=6.0. Fluorescence
      decay measurements of intrinsic enzyme fluorescence, mainly due to tryptophan
      residues, in the different reverse micellar systems were also carried out, in an
      attempt to obtain some insight on the effect of the organic solvent on the
      protein conformation. Differences observed in the kinetics of the fluorescence
      decays of tryptophan residues of the lipase incorporated to the micelles with the
      different external organic solvents were also found in the catalytic behaviour of
      the enzyme. In particular, it is observed that the contribution of the long lived
      component of the fluorescence decay is considerably higher (ca. 40%) in aliphatic
      than in aromatic solvents (ca. 15%), indicating significant differences in the
      protein conformation. This effect of the organic solvent on the protein
      conformation is also observed in the enzymatic activity, which is higher in the
      aromatic than in the aliphatic solvents.

PMID- 17522968
TI  - Isolation and characterization of a serine protease, Ba III-4, from Peruvian
      Bothrops atrox venom.
AB  - A serine protease from Bothrops atrox (Peruvian specimen's venom) was isolated in
      two chromatographic steps in LC molecular exclusion and reverse phase-HPLC. This
      protein was denominated Ba III-4 (33,080.265 Da determinated by MALDI-TOF mass
      spectrometry) and showed pI of 5.06, Km 0.2 x 10(-1 ) M and the V (max) 4.1 x 10(
      1 )nmoles p-NA/lt/min on the synthetic substrate BapNA. Ba III-4 also showed
      ability to coagulate bovine fibrinogen. The serine protease was inhibited by
      soyben trypsin inhibitor and DA2II, which is an anti-hemorrhagic factor isolated
      from the opossum specie Didelphis albiventris. The primary structure of Ba III-4
      showed the presence of His(44), Asp(94) and Ser(193) residues in the
      corresponding positions to the catalytic triad established in the serine
      proteases and Ser(193) are inhibited by phenylmethylsulfonylfluoride (PMSF).
      Amino acid analysis showed a high content of Asp, Glu, Gly, Ser, Ala and Pro, as
      well as 12 half-cysteine residues. Ba III-4 contained 293 amino acid residues and
      the primary structure of VIGGDECDIN EHPFLAFMYY SPRYFCGMTL INQEWVLTAA HCRYFCGMTL
      IHLGVHRESE KANYDEVRRF PKEKYFIFCD NNFTDDEVDK DIMLIRLDKP VSNSEHIAPL SLPSNPPSVG
      SVCRIMGWGQ TTTSPIDVLS PDEPHCANIN LFDNTVCHTA HPQVANTRTS TDTLCAGDLQ GGRDTCNGDS
      GGPLICNEQL HGILSWGGDP CAQPNKPAFY TKVYYFDHPW IKSIIAGNKK TVNFTCPPLR SDAKDDSTTY
      INQEWDWVLT AEHCDRTHMR NSFYDYSSIN SDS. Titration experiments did not show the
      presence of free sulfhydryl groups after 4 h incubation, nor were differences
      found in relation to titration kinetics in the presence of nondenaturating
      buffer. The isolation of this protein, Ba III-4, is of potential interest for the
      understanding of the pathomechanism of the snake venom action and for the
      identification of new blood coagulation enzymes of natural sources.

PMID- 17522969
TI  - Characterization of protomer interfaces in HslV protease; the bacterial homologue
      of 20S proteasome.
AB  - HslVU, a two-component proteasome-related prokaryotic system is composed of HslV
      protease and HslU ATPase. HslV protomers assemble in a dodecamer of two-stacked
      hexameric rings that form a complex with HslU hexamers. The intra- and inter-ring
      protomer interfaces in the HslV dodecamer underpin the integrity and
      functionality of HslVU. Structural characterization of HslV from different
      bacteria illustrated considerable differences in interacting residues, accessible
      surface and gap volumes at the intra-ring interface that is primarily stabilized
      by polar interactions. Amino acid residues Lys28, Arg83 and Asp111 have envisaged
      as hot spots at this HslU-interacting interface. The inter-ring interfaces that
      are made up of side chain packing of hydrophobic residues are structurally
      conserved. Hyperthermostable bacterium T. maritima HslV has extensively networked
      polar/nonpolar interactions and highly packed environment at all interfaces.
      Present data demonstrates that HslV protomer interfaces perform distinct
      functions; whereas intra-ring interface participates in HslV:HslU interaction
      resulting in allosteric activation of HslV protease by HslU, the inter-ring
      interfaces uphold the oligomeric form of HslV.

PMID- 17522970
TI  - Masculinity and intentions to perform health behaviors: the effectiveness of fear
      control arguments.
AB  - This study examined the impact of fear control and danger control messages on
      intentions to perform health behaviors. It was hypothesized that persons high in
      masculinity would be more influenced by messages that address fear than messages
      that exclusively focus on the efficacy of the behavior (danger control). To test
      this proposition, 172 participants were classified into high and low masculinity
      groups according to their scores on the Bem Sex Role Inventory, and randomly
      assigned fear reducing or danger control messages either encouraging detection
      behavior (skin cancer self-examination) or promotion behavior (sunscreen usage).
      Highly masculine participants demonstrated greater behavioral intentions and more
      positive attitudes about the behavior when exposed to a fear-reducing message.
      The results suggest that it is possible to motivate adaptive health behavior even
      when a person is engaging in fear control.

PMID- 17522971
TI  - Religiousness/spirituality and health: a meaning systems perspective.
AB  - The existence of links between religion and spirituality (R/S) and health appear
      to be firmly established, but much less is known about how these various aspects
      of R/S are translated into health outcomes. Within a meaning systems framework,
      this article reviews and integrates findings regarding the many pathways through
      which R/S may influence physical health and well-being. In particular, evidence
      for the pathways of body sanctification, meaning in life, social support, health
      locus of control, health behaviors, positive and negative affect and stress
      moderation, treatment adherence, and coping is examined. The article concludes
      with suggestions for future research.

PMID- 17522972
TI  - Psychometric properties of the Perceived Diabetes Self-Management Scale (PDSMS).
AB  - Patients with chronic medical conditions such as diabetes mellitus need to self
      manage their condition for optimal outcomes. The degree to which patients with
      diabetes feel competent or self-efficacious in managing their diabetes has been
      related to behaviors such as dieting or exercise as well as to indicators of
      glycemic control. A diabetes-specific adaptation of the Perceived Medical
      Condition Self-Management Scale was administered to 398 patients with either type
      1 (n=57) or type 2 (n=341) diabetes. Cronbach's alpha of the 8-item Perceived
      Diabetes Self-Management Scale (PDSMS) was .83 indicating internal consistency.
      PDSMS scores were uncorrelated with age, years since diagnosis, and years of
      schooling, but were negatively correlated with body mass index. Those with type 1
      DM had higher PDSMS scores than those with type 2 DM. PDSMS scores were
      positively correlated with a number of self-reported self-care activities and
      negatively related to measures of glycemic control. The PDSMS is a valid measure
      of diabetes self-efficacy, and the more generic template from which it was
      adapted can easily be altered for use with other chronic medical conditions.

PMID- 17522973
TI  - Does distraction facilitate problem-focused coping with job stress? A 1 year
      longitudinal study.
AB  - This study examined the sole and combined effects of problem-focused coping and
      distraction on employee well-being (i.e., stress responses and job performance)
      using two-wave panel survey data with a 1-year time lag. Participants were 488
      male employees, who worked for a construction machinery company in western Japan.
      Hierarchical multiple regression analyses were conducted to examine whether
      distraction moderates the relationship of problem-focused coping with well-being.
      More use of problem-focused coping was negatively related to subsequent stress
      responses among those high in distraction. The combination of high problem
      focused coping and high distraction was positively related to subsequent job
      performance, although it was limited only to the high job stress situation.
      Results suggest that the combination of high problem-focused coping and high
      distraction may lead to lower stress responses and better performance (but only
      in high job stress situations for performance) than the combination of high
      problem-focused coping and low distraction, at least for male blue-collar
      workers.

PMID- 17522974
TI  - Risk of familial breast cancer is not increased after pregnancy.
AB  - Risk of breast cancer is temporarily elevated shortly after pregnancy and the
      available limited data suggest that a family history of breast cancer may
      reinforce the risk. We used the nation-wide Swedish Family-Cancer Database to
      estimate the relative risk (RR) for invasive breast cancer following childbirth
      among women with or without a family history. The RRs were defined using Poisson
      regression model of person-years as offset, adjusted for age, period and age at
      first childbirth. For women without a family history, RRs for breast cancer
      showed a U-shaped pattern after last pregnancy. Among the 5,217 patients with a
      first-degree family history the familial risk was 1.77; there was no evidence of
      increased RRs immediately after last pregnancy. The present study is by far the
      largest one published on the theme. It shows that pregnancy is not an additional
      risk factor for women with a family history.

PMID- 17522975
TI  - Postconditioning in man.
AB  - Acute myocardial infarction is the leading cause of morbidity and mortality in
      industrialized countries. Ischemic postconditioning, that consists of repeated
      brief episodes of ischemia-reperfusion performed just after reflow following a
      prolonged ischemic insult, dramatically reduces infarct size in animal models.
      Recent data indicate that it might involve the activation of the PI3-kinase-Akt
      eNOS as well as PKC signalling pathways and inhibition of the opening of the
      permeability transition pore. A recent clinical study demonstrated that
      postconditioning protects the human heart. Repeated brief episodes of inflation
      deflation of the angioplasty balloon performed immediately after re-opening of
      the culprit coronary artery reduced infarct size by 36%. Additional studies are
      required to determine whether infarct size limitation by postconditioning would
      improve functional recovery as well as patient's outcome. Further research is
      needed to find new pharmacological agents that would mimick postconditioning in
      order to treat all patients with ongoing acute myocardial infarction.

PMID- 17522976
TI  - 12-lipoxygenase induces apoptosis of human gastric cancer AGS cells via the
      ERK1/2 signal pathway.
AB  - 12-Lipoxygenase (12-LOX) is over-expressed in a variety of human tumors, but its
      exact effect on the tumorogenesis of gastric cancer remains largely obscure. To
      investigate the effect of 12-LOX and its inhibitor baicalein on proliferation and
      apoptosis of human gastric cancer, AGS cells were separately treated with 12
      hydroxyeicosatetraenoic acid (12-HETE, a metabolite of 12-LOX) and baicalein. MTT
      assay revealed that the absorbance of the 12-HETE-treated group was significantly
      (P < 0.01) higher than that of control group and that the absorbance of baicalein
      treated group was significantly (P < 0.01) less than that of the control group,
      and that 48 h after treatment the apoptosis index of the baicalein-treated group
      was significantly (P < 0.01) higher than that of the untreated group and was
      significantly (P < 0.01) lower in the 12-HETE-treated group. Western blotting
      analysis was used to investigate the mechanism of these effects. The results
      revealed that the concentration of phosphorylated ERK in cells treated with 100
      nmol L(-1) 12-HETE was significantly (P < 0.05) higher than in the untreated
      group and that the concentration of phosphorylated ERK1/2 in cells treated with
      40 micromol L(-1) baicalein was significantly (P < 0.05) lower than in the
      untreated group. The expression level of bcl-2 was up-regulated and down
      regulated after separate treatment with 12-HETE and baicalein, respectively, and
      both of these effects could be blocked by PD98059. Protein kinase C (PKC)
      activity was increased by treatment with 12-HETE and reduced by treatment with
      baicalein (P < 0.05). The PKC inhibitor BIM (bisindolymaleimide-I) blocked the
      phosphorylation of ERK1/2 and activation of PKC induced by 12-LOX. When
      pretreated with BIM, the concentration of phospho-ERK1/2 or bcl-2 in the BIM + 12
      HETE-treated group was significantly (P < 0.05) lower than in that treated with
      12-HETE only, and the concentration in the BIM + baicalein-treated group was
      significantly (P < 0.05) higher than in that treated with baicalein only. On the
      basis of these data we conclude that, via its metabolite 12-HETE, 12-LOX
      abolishes proliferation of AGS cells and protect cells from apoptosis by
      activating the ERK1/2 pathway and, eventually, enhances expression of bcl-2.
      Because PKC is also involved in the activation of ERK1/2 induced by 12-LOX, 12
      LOX inhibitors would be potentially powerful anticancer agents for prevention and
      cure of human gastric cancer.

PMID- 17522977
TI  - Cyclic pressure stimulates DNA synthesis through the PI3K/Akt signaling pathway
      in rat bladder smooth muscle cells.
AB  - Previous studies demonstrated that the bladder exhibited severe tissue remodeling
      following spinal cord injury. In such pathological bladders, uninhibited non
      voiding contractions subject bladder cells to cyclic oscillations of intravesical
      pressure. We hypothesize that cyclic pressure is a potential trigger for tissue
      remodeling in overactive bladder. Using a custom-made setup, rat bladder smooth
      muscle cells (SMC) in vitro were exposed to cyclic hydrostatic pressure (40 cm
      H2O) at either 0.1 Hz or 0.02 Hz frequency for up to 24 h. When compared to
      static control and cells exposed to 0.02-Hz cyclic pressure, SMC exposed to 0.1
      Hz cyclic pressure contained significantly (p < 0.05) higher amounts of DNA. We
      confirmed that the increase in DNA was due to increased cell proliferation,
      indicated by increased BrdU incorporation, but not due to decreased apoptosis
      rates in response to cyclic pressure. In addition, significant (p < 0.05)
      elevation of Akt phosphorylation in SMC following exposure to cyclic pressure and
      lack of pressure-induced SMC hyperplasia in the presence of PI3K inhibitors,
      wortmannin and LY294002, indicated the involvement of the PI3K/Akt pathway in the
      proliferative response of SMC to cyclic pressure. We concluded that chronic
      exposure to intravesical pressure oscillation may be a potential trigger for
      bladder tissue remodeling.

PMID- 17522978
TI  - Effect of food consistency on the degree of mineralization in the rat mandible.
AB  - A switch to a soft diet, associated with reduced forces applied to the mandible
      during mastication, may result in an alteration of the degree of mineralization
      in the mandible. This alteration may be regionally different. The aim of this
      study was to analyze this alteration by examination of the degree of
      mineralization in the mandible of growing rats fed with a hard or soft diet.
      Fifteen Wistar male rats were used in this investigation. After weaning, six rats
      were fed with a hard diet and the remaining nine rats with a soft diet. After 9
      weeks, three-dimensional reconstructions of the cortical and trabecular bone of
      their mandibles were obtained using a microCT system. The degree of
      mineralization was determined for the trabecular bone in the condyle and for the
      cortical bone in the anterior and posterior areas of the mandibular body. In both
      diet groups the degree of mineralization was significantly (p < 0.01) lower in
      the trabecular than in the cortical bone. In the mandibular body, the anterior
      area showed a significantly (p < 0.01) higher degree of mineralization than the
      posterior area in both diet groups. In both areas the soft diet group had a
      significantly (p < 0.05 or 0.01) higher degree of mineralization than the hard
      diet group. The trabecular bone in the condyle of the hard diet group showed a
      significantly (p < 0.01) higher degree of mineralization than in the soft diet
      group. The present results indicate the importance of proper masticatory muscle
      function for craniofacial growth and development.

PMID- 17522979
TI  - Biomolecular motor-driven microtubule translocation in the presence of shear
      flow: modeling microtubule deflection due to shear.
AB  - We have previously demonstrated that shear flow aligns microtubules moving on
      kinesin-coated microchannels with the flow direction, and statistically analyzed
      the rate of microtubule alignment under different concentrations of kinesin as
      well as strengths of shear flow. These data qualitatively support the hypothesis
      that the alignment results from the leading ends of translocating microtubules
      bending into the direction of the flow due to viscous drag force. Here, we
      present a cantilever-beam model that quantitatively shows agreement between this
      hypothesis and observation. Specifically, the model couples the exact nonlinear
      solution for cantilever-beam deflection with drag coefficients determined by
      numerical simulations of microtubules in the presence of shear flow near a wall.
      Coupled with flexural rigidity results of our previous study (which used electric
      fields), the established model successfully predicts new experimental data for
      microtubule bending in response to shear flow, further supporting our hypothesis
      for the mechanism of microtubule alignment. We expect that the newly-calculated
      drag coefficients and beam-bending model may be useful for biophysical studies as
      well as interpretation of in vivo data and the design of kinesin/microtubule
      based devices.

PMID- 17522981
TI  - Malonyl coenzyme A affects insulin-stimulated glucose transport in myotubes.
AB  - There seems to be an association between increased concentrations of malonyl
      coenzyme A (malonyl CoA) in skeletal muscle and diabetes and/or insulin
      resistance. The purpose of the current study was to test the hypothesis that
      treatments designed to manipulate malonyl CoA concentrations would affect insulin
      stimulated glucose transport in cultured C2C12 myotubes. We assessed glucose
      transport after polyamine-mediated delivery of malonyl CoA to myotubes, after
      incubation with dichloroacetate (which reportedly increases malonyl CoA levels),
      or after exposure of myotubes to 2-bromopalmitate, a carnitine palmitoyl
      transferase I inhibitor. All three of these treatments prevented stimulation of
      glucose transport by insulin. We also assayed glucose transport after 30 min of
      inhibition of acetyl coenzyme A carboxylase (ACC), the enzyme which catalyzes the
      production of malonyl CoA. Three unrelated ACC inhibitors (diclofop, clethodim,
      and Pfizer CP-640186) all enhanced insulin-stimulated glucose transport. However,
      none of the treatments designed to manipulate malonyl CoA concentrations altered
      markers of proximal insulin signaling through Akt. The findings support the
      hypothesis that acute changes in malonyl CoA concentrations affect insulin action
      in muscle cells but suggest that the effects do not involve alterations in
      proximal insulin signaling.

PMID- 17522982
TI  - Intra-uterine origins of type 2 diabetes.
AB  - Epidemiological studies have linked low birth weight with an increased risk of
      type 2 diabetes in later life. This finding has been observed in many populations
      worldwide, in many different ethnic and socio-economic groups. These studies led
      to the proposal of the 'thrifty phenotype hypothesis' that suggests that the
      foetal environment plays a major role in mediating this relationship. Here we
      review the human studies and those in animal models which support the 'thrifty
      phenotype hypothesis'. Molecular pathways underlying the mechanisms by which a
      suboptimal foetal environment leads to increased risk of type 2 diabetes are
      discussed, along with future directions outlining how these pathways and
      programming events can be further dissected to discover plausible intervention
      strategies to reduce type 2 diabetes.

PMID- 17522983
TI  - Ferritin and ferritin isoforms I: Structure-function relationships, synthesis,
      degradation and secretion.
AB  - Ferritin is the intracellular protein responsible for the sequestration, storage
      and release of iron. Ferritin can accumulate up to 4500 iron atoms as a
      ferrihydrite mineral in a protein shell and releases these iron atoms when there
      is an increase in the cell's need for bioavailable iron. The ferritin protein
      shell consists of 24 protein subunits of two types, the H-subunit and the L
      subunit. These ferritin subunits perform different functions in the
      mineralization process of iron. The ferritin protein shell can exist as various
      combinations of these two subunit types, giving rise to heteropolymers or
      isoferritins. Isoferritins are functionally distinct and characteristic
      populations of isoferritins are found depending on the type of cell, the
      proliferation status of the cell and the presence of disease. The synthesis of
      ferritin is regulated both transcriptionally and translationally. Translation of
      ferritin subunit mRNA is increased or decreased, depending on the labile iron
      pool and is controlled by an iron-responsive element present in the 5'
      untranslated region of the ferritin subunit mRNA. The transcription of the genes
      for the ferritin subunits is controlled by hormones and cytokines, which can
      result in a change in the pool of translatable mRNA. The levels of intracellular
      ferritin are determined by the balance between synthesis and degradation.
      Degradation of ferritin in the cytosol results in complete release of iron, while
      degradation in secondary lysosomes results in the formation of haemosiderin and
      protection against iron toxicity. The majority of ferritin is found in the
      cytosol. However, ferritin with slightly different properties can also be found
      in organelles such as nuclei and mitochondria. Most of the ferritin produced
      intracellularly is harnessed for the regulation of iron bioavailability; however,
      some of the ferritin is secreted and internalized by other cells. In addition to
      the regulation of iron bioavailability ferritin may contribute to the control of
      myelopoiesis and immunological responses.

PMID- 17522980
TI  - Lung ischemia-reperfusion injury: implications of oxidative stress and platelet
      arteriolar wall interactions.
AB  - Pulmonary ischemia-reperfusion (IR) injury may result from trauma,
      atherosclerosis, pulmonary embolism, pulmonary thrombosis and surgical procedures
      such as cardiopulmonary bypass and lung transplantation. IR injury induces
      oxidative stress characterized by formation of reactive oxygen (ROS) and reactive
      nitrogen species (RNS). Nitric oxide (NO) overproduction via inducible nitric
      oxide synthase (iNOS) is an important component in the pathogenesis of IR.
      Reaction of NO with ROS forms RNS as secondary reactive products, which cause
      platelet activation and upregulation of adhesion molecules. This mechanism of
      injury is particularly important during pulmonary IR with increased iNOS activity
      in the presence of oxidative stress. Platelet-endothelial interactions may play
      an important role in causing pulmonary arteriolar vasoconstriction and post
      ischemic alveolar hypoperfusion. This review discusses the relationship between
      ROS, RNS, P-selectin, and platelet-arteriolar wall interactions and proposes a
      hypothesis for their role in microvascular responses during pulmonary IR.

PMID- 17522984
TI  - Health-related quality of life during the first year after severe brain trauma
      with and without polytrauma.
AB  - OBJECTIVE: The increasing number of patients surviving severe traumatic brain
      injury (sTBI) but with significant sensorimotor and neuropsychological deficits
      is a challenge to rehabilitation medicine. So far, most research initiatives have
      focused on mortality rates, physiological or economic parameters to estimate
      therapeutic effects of rehabilitation strategies. Investigations on health
      related quality of life (HRQoL) after TBI with and without concomitant polytrauma
      are rare compared to other disorders. DESIGN/PATIENTS: A prospective study was
      conducted to investigate HRQoL using the SF-36 questionnaire in 49 patients with
      sTBI (Glasgow Coma Scale < 9 for more than 24 hours) with and without concomitant
      polytrauma 6 and 12 months after injury. RESULTS: The SF-36 score profiles 6 and
      12 months after trauma were similar. Scores 12 months after trauma, however, were
      higher in 7/8 dimensions indicating an improvement over time. Similar
      observations were made for physical and mental sum scores. There was no
      difference in the SF-36 scoring pattern between the patients with isolated TBI
      and the patients with concomitant polytrauma, except for physical functioning
      after 12 months. CONCLUSION: While there is significant overall improvement of
      HRQoL over time, sTBI appears to bear major influence on post-traumatic HRQoL and
      outcome.

PMID- 17522985
TI  - Sick leave, disability pension and health-care-seeking behaviour prior to stroke,
      among people aged 30-65: a case-control study.
AB  - PRIMARY OBJECTIVE: To explore sick leave, disability pension and health-care
      seeking behaviour among people 30-65 years of age prior to their stroke in 2001
      in the county of Ostergotland, Sweden. RESEARCH DESIGN: A register-based,
      retrospective case-control study for the period 1 January 1998-31 December 2000.
      Cases (n=212): patients aged 30-65 with first-ever stroke in 2001. Controls
      (n=4606): people aged 30-65, randomly selected from the same base population.
      MAIN OUTCOMES AND RESULTS: More than 91 days of accumulated sick leave among
      women was associated with increased likelihood of developing stroke (OR=1.89).
      Among men, 29-90 days and more than 91 days on sick leave increased the
      likelihood of stroke (OR=2.34 and OR=3.43, respectively). CONCLUSION: Frequent
      health-care-seeking behaviour is not a tool for identifying women who develop
      stroke, while it may be an indicator for men. Accumulated sick leave may be a
      tool for identifying men and women with higher risk of stroke.

PMID- 17522986
TI  - Achieving a successful and sustainable return to the workforce after ABI: a
      client-centred approach.
AB  - PRIMARY OBJECTIVE: This paper describes the approach used by the Victorian
      Acquired Brain Injury (ABI) specialist team of CRS Australia (formerly
      Commonwealth Rehabilitation Service) to facilitate participation in the workforce
      for its clients. The approach and results achieved are compared and contrasted
      with other models nationally and internationally. METHOD AND PROCEDURES: This two
      part study involves a survey of the specialist team members regarding use and
      efficacy of assessment and intervention strategies and data mining of closed case
      files to identify predictors of sustainable employment outcomes for people with
      ABI. MAIN OUTCOMES AND RESULTS: CRS Australia's results compare favourably with
      other published results (50% achieved a minimum of 13 weeks open employment
      compared to population estimates of 38-46.5%). Results were achieved with people
      with mild, moderate and severe injury. Assessments and interventions that
      correlate with successful employment outcome are described. CONCLUSIONS: A client
      centred approach, combining specialist ABI expertise, skilled assessment and
      practical workplace-based interventions results in favourable employment outcome
      rates.

PMID- 17522987
TI  - Changes in coping strategies, social support, optimism and health-related quality
      of life following traumatic brain injury: a longitudinal study.
AB  - PRIMARY OBJECTIVE: To study longitudinal changes in psychological coping
      strategies, social support, life orientation and health-related quality of life
      in the late period after traumatic brain injury (TBI). SUBJECTS: Thirty-one
      patients with TBI who were first investigated on average 2.3 years after injury
      and were prospectively followed on average 5.7 years later. METHODS: Estonian
      versions of the COPE-D Test, the Brief Social Support Questionnaire, the Life
      Orientation Test and the RAND-36 questionnaire. RESULTS: During the late follow
      up period health-related quality of life and resuming work did not improve
      significantly. Persons with TBI reported an increase in seeking social/emotional
      support (p<0.05), frequent use of avoidance-oriented styles and reduced use of
      task-oriented styles. This was accompanied by low social support and low
      satisfaction with support, both of which were associated with health-related
      quality of life and resuming work after TBI. Although the patients had become
      more optimistic (p<0.05), this did not correlate with their health status and
      social well-being. CONCLUSIONS: This prospective study revealed maladaptive
      changes in the profile of coping strategies and an increase in optimism. As
      social support, satisfaction with support and health-related quality of life did
      not improve, then rehabilitation, social and psychological support are
      continuously needed.

PMID- 17522988
TI  - Methylphenidate effect on hemispheric attentional imbalance in patients with
      traumatic brain injury: a psychophysical study.
AB  - PRIMARY OBJECTIVE: We found spatially asymmetric allocation of attention in
      patients with traumatic brain injury (TBI) without overt asymmetry on
      neurological examination. The possible effect of Methylphenidate in reducing this
      asymmetry is evaluated in the current research. RESEARCH DESIGN: Psychophysical
      study using a visual spatial attention task. Identification rates were measured
      after precuing attention to different visual field loci. TBI patients were tested
      before, during and after administration of Methylphenidate. METHODS AND
      PROCEDURES: After precuing to a locus 5 degrees into the left or right hemifield,
      target patterns were presented briefly at the cued location (valid), or on the
      opposite side (invalid) - requiring an attentional shift. Patients were treated
      with a gradually increasing dosage of a psychostimulant over two weeks, followed
      by a similar two-week period of gradually diminishing dosage. Patients were
      tested before treatment, at its peak, and (twice) following its completion. MAIN
      OUTCOME AND RESULTS: Patients demonstrated significantly worse performance with
      leftward than with rightward cross-hemifield shifts of attention. This difference
      was significantly reduced during and following treatment. CONCLUSIONS: Asymmetric
      performance and improvement with treatment suggest that diffuse TBI damage leads
      to a lateralized attention-related deficit. These findings support the hypotheses
      that attention is a distributed and asymmetrically lateralized function. The
      findings are consistent with the conclusion that Methylphenidate may be an
      effective treatment for attentional deficits in TBI patients.

PMID- 17522989
TI  - The impact of prophylactic treatment on post-traumatic epilepsy after severe
      traumatic brain injury.
AB  - AIM: To assess the incidence of late post-traumatic epilepsy (PTE) in patients
      with very severe traumatic brain injury (TBI) who either received or did not
      receive anti-epileptic prophylactic treatment. METHODS: Two populations were
      studied: 55 patients retrospectively and 82 subjects prospectively. RESULTS: Ten
      patients (18%) in the first population showed late PTE. Although the incidence
      was lower in patients who did not receive prophylactic treatment, the difference
      between the treated and the non-treated group was not statistically significant.
      Sixty-nine patients in the second group (84%) had prophylactic treatment. Twenty
      seven patients (39%) suffered from late PTE during the 2-year follow-up period
      and 17 of them (63%) showed EEG epileptic abnormalities. No patient who did not
      receive preventive therapy suffered from late PTE during the observation period.
      CONCLUSIONS: Due to the negative cognitive effects of anti-epileptic drugs, the
      preliminary results are of considerable interest for the rehabilitation of
      patients with very severe TBI.

PMID- 17522990
TI  - Overview and inter-rater reliability of an incident-based rating scale for
      aggressive behaviour following traumatic brain injury: The Overt Aggression Scale
      Modified for Neurorehabilitation-Extended (OAS-MNR-E).
AB  - PRIMARY OBJECTIVE: The presentation and evaluation of the Overt Aggression Scale
      Modified for Neurorehabilitation-Extended (OAS-MNR-E). RESEARCH DESIGN: Inter
      rater reliability study using data collection procedures mirroring clinical
      practice. METHODS AND PROCEDURES: Fifteen clinical staff representing five
      different disciplines received a 30-minute orientation to the study and a 30
      minute overview of the OAS-MNR-E. There were 34 patients who engaged in a
      rateable behaviour and were observed by two raters. There were 199 observed
      aggressive behaviours during the 6-week study period. MAIN OUTCOMES AND RESULTS:
      All sub-scales of the OAS-MNR-E had high percentage agreement (>92%) and the
      kappa statistic was uniformly excellent (>0.77). Multiple ratings within a sub
      scale resulted in lower reliabilities. Incidents with multiple interventions were
      of longer duration. Interventions were on average more intrusive when used in
      combination than when used singly. CONCLUSIONS: The OAS-MNR-E can be easily
      incorporated into facility routines and is reliable. The rating tool reported
      here can provide data that assists in programme design, evaluation and treatment
      planning.

PMID- 17522991
TI  - Comparison of the O-Log and GOAT as measures of posttraumatic amnesia.
AB  - PRIMARY OBJECTIVE: To compare PTA severity and duration assessments made by
      Orientation Log (O-Log) and the Galveston Orientation and Amnesia Test (GOAT) and
      the relationship of data yielded by these assessments to rehabilitation outcomes.
      RESEARCH DESIGN: Retrospective study. METHODS AND PROCEDURES: O-Log, GOAT,
      demographic, length of stay, and Functional Independence Measure (FIM) data among
      83 inpatient subjects with recent TBI requiring inpatient care were reviewed.
      MAIN OUTCOMES AND RESULTS: PTA severity and duration as assessed by the O-Log and
      the GOAT are statistically similar and correlate similarly with rehabilitation
      LOS and discharge total FIM score. Simple linear regression models suggest that O
      Log scores better predict rehabilitation outcomes than GOAT scores. CONCLUSIONS:
      Although the O-Log and GOAT perform similarly as measures of PTA severity and
      duration, PTA assessments using the O-Log offers better prediction of
      rehabilitation outcomes. Further study of the O-Log as an alternate assessment of
      PTA is warranted.

PMID- 17522992
TI  - Assessing adaptive behaviour in the post-acute setting following traumatic brain
      injury: initial reliability and validity of the Adaptive Behaviour and Community
      Competency Scale (ABCCS).
AB  - PRIMARY OBJECTIVE: Present the rationale for adaptive behavior rating and
      introduce the Adaptive Behaviour and Community Competency Scale (ABCCS), a
      comprehensive and detailed measure of adaptive behaviour, for use with persons
      with traumatic brain injury (TBI) in the post-acute period. METHODS AND
      PROCEDURES: Direct-care staff with limited exposure to the ABCCS, completed it
      twice, two weeks apart, about persons with TBI who were resident in diverse
      community settings. Other measures to assess validity were administered
      concurrently. RESULTS: Intraclass Correlation Coefficients (ICC) for interrater
      and test-retest reliability of the ABCCS were excellent (ICC=0.9681 and 0.9860
      respectively). Evidence for convergent and divergent validity with comparison
      measures was strong with highly significant correlations with scales measuring
      similar content (Rho=0.613-0.919) and weak correlations for scales measuring
      dissimilar content (Rho=0.318-0.397). CONCLUSIONS: The ABCCS is a reliable and a
      valid indicator of functioning post-acute TBI and is straightforward enough to be
      used by direct-care staff.

PMID- 17522993
TI  - A comparison of four prompt modes for route finding for community travellers with
      severe cognitive impairments.
AB  - PRIMARY OBJECTIVE: Navigational skills are fundamental to community travel and,
      hence, personal independence and are often disrupted in people with cognitive
      impairments. Navigation devices are being developed that can support community
      navigation by delivering directional information. Selecting an effective mode to
      provide route-prompts is a critical design issue. This study evaluated the
      differential effects on pedestrian route finding using different modes of
      prompting delivered via a handheld electronic device for travellers with severe
      cognitive impairments. RESEARCH DESIGN: A within-subject comparison study was
      used to evaluate potential differences in route navigation performance when
      travellers received directions using four different prompt modes: (1) aerial map
      image, (2) point of view map image, (3) text based instructions/no image and (4)
      audio direction/no image. METHODS AND PROCEDURES: Twenty travellers with severe
      cognitive impairments due to acquired brain injury walked four equivalent routes
      using four different prompting modes delivered via a wrist-worn navigation
      device. Navigation scores were computed that captured accuracy and confidence
      during navigation. MAIN OUTCOME: Results of the repeated measures Analysis of
      Variance suggested that participants performed best when given prompts via speech
      based audio directions. The majority of the participants also preferred this
      prompting mode. Findings are interpreted in the context of cognitive resource
      allocation theory.

PMID- 17522994
TI  - Postoperative parkinsonism and lupus anticoagulant: a model of autoantibody
      mediated neurotoxicity in stress.
AB  - PRIMARY OBJECTIVE: Nigrostriatal hypodopaminergism is the fundamental basis in
      parkinsonism. It may arise secondarily from a variety of disorders but is rarely
      mentioned shortly after surgery. METHODS AND PROCEDURES: To report the clinical
      course of five patients who had had symptomatic parkinsonism developed shortly
      after surgery (lumbar laminectomy, prostatectomy and cholestectomy). Appropriate
      investigations were done to elucidate their pathogenesis. MAIN OUTCOMES AND
      RESULTS: There was no remarkable finding of their anesthetic agents, duration of
      surgery, type of surgery, medical conditions or preoperative screening test.
      Extensive investigations did not reveal consistent abnormality. However, an
      abnormal presence of lupus anticoagulant was detected in four patients; primary
      antiphospholipid antibody syndrome was fulfilled in two of them. The lupus
      anticoagulant restored to the reference range in another two patients later.
      Catastrophic antiphospholipid antibody syndrome was not seen. Initially, their
      parkinsonian symptoms rapidly progressed but slowed down after six months.
      CONCLUSION: Lupus anticoagulant possesses neurotoxic property and has been found
      in cases of movement disorder involving with the central dopaminergism. Surgery,
      a form of traumatic stress, has been reported to bring on lupus anticoagulant and
      catastrophic antiphospholipid antibody syndrome. These relationships remind a
      generation or an enhancement of pathognomic autoantibody vulnerable for
      dopaminergic toxicity, such as lupus anticoagulant or other antiphospholipid
      antibody.

PMID- 17522995
TI  - Matrix biology of abdominal aortic aneurysms in diabetes: mechanisms underlying
      the negative association.
AB  - Several case-control studies have shown a significant negative association
      between diabetes and abdominal aortic aneurysm (AAA). This interaction has the
      potential to further our understanding of these two diseases but has attracted
      little research. The changes seen in the walls of aneurysmal aortas include
      inflammation and the activation of proteolytic pathways resulting in loss of
      elastin and other structural proteins. In contrast, diabetes is associated with
      increased synthesis and reduced degradation of matrix. The deposition of advanced
      glycation end products also renders vascular matrix resistant to proteolysis in
      diabetic patients. The aim of our present minireview is to compare the changes in
      matrix biology seen in diabetes and AAA and to explore molecular mechanisms that
      may explain the negative association and identify possible therapeutic
      implications.

PMID- 17522996
TI  - Human mesenchymal stem cells derived from bone marrow display a better
      chondrogenic differentiation compared with other sources.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation
      into several mesodermal lineages. These cells have been isolated from various
      tissues, such as adult bone marrow, placenta, and fetal tissues. The comparative
      potential of these cells originating from different tissues to differentiate into
      the chondrogenic lineage is still not fully defined. The aim of our study was to
      investigate the chondrogenic potential of MSCs isolated from different sources.
      MSCs from fetal and adult tissues were phenotypically characterized and examined
      for their differentiation capacity, based on morphological criteria and
      expression of extracellular matrix components. Our results show that both fetal
      and adult MSCs have chondrogenic potential under appropriate conditions. The
      capacity of bone marrow-derived MSCs to differentiate into chondrocytes was
      reduced on passaging of cells. MSCs of bone marrow origin, either fetal or adult,
      exhibit a better chondrogenesis than fetal lung- and placenta-derived MSCs, as
      demonstrated by the appearance of typical morphological features of cartilage,
      the intensity of toluidine blue staining, and the expression of collagen type II,
      IX, and X after culture under chondrogenic conditions. As MSCs represent an
      attractive tool for cartilage tissue repair strategies, our data suggest that
      bone marrow should be considered the preferred MSC source for these therapeutic
      approaches.

PMID- 17522997
TI  - Fibromodulin interactions with type I and II collagens.
AB  - Fibromodulin is a keratan-sulfate small leucine-rich proteoglycan (SLRP)
      regulating collagen I and II fibril formation. In vivo studies suggest that,
      alongside decorin, fibromodulin plays an important role in the maintenance of
      mature tissues. To characterize fibromodulin/decorin differences in binding to
      type I and II collagen, we tested the collagen CNBr peptides in solid-phase
      assays. Only one peptide from collagen II and several peptides from collagen I
      interacted with fibromodulin, pointing to multiple binding sites in the collagen
      I molecule. By Scatchard-type analysis, the fibromodulin molecule showed only one
      class of binding sites for collagen I and both low and high affinity (classes of)
      binding sites for collagen II. Lys/Hyl residues in both collagens are essential
      for the interaction. Fibril formation assays showed the concomitant presence of
      fibromodulin and decorin in fibrils and a cumulative inhibitory effect. In solid
      phase assays decorin seems to inhibit fibromodulin binding, whereas the contrary
      does not occur. We found fibromodulin and decorin have similarities and
      differences that may represent the biochemical basis of redundancy in SLRP
      function with compensation between different (classes of) SLRPs.

PMID- 17522998
TI  - Modulation of intracellular reactive oxygen species level in chondrocytes by IGF
      1, FGF, and TGF-beta1.
AB  - Growth factors are important in the development, maintenance and repair of
      cartilage. The principal aim of this study was to test the capacity of three
      growth factors with established roles in cartilage, namely insulin-like growth
      factor (IGF)-1, fibroblast growth factor (FGF) and transforming growth factor
      (TGF)-beta 1, to alter intracellular reactive oxygen species (ROS) levels.
      Explants of articular cartilage from young, mature, and aged rats were pretreated
      with IGF-1, FGF, or TGF-beta 1 and intracellular ROS levels were quantified using
      the free radical sensing probe dihydrorhodamine 123 (DHR 123), confocal
      microscopy, and densitometric image analysis. Viability of chondrocytes following
      ROS stress and growth factor treatment was assessed using the live/dead
      cytotoxicity assay, and the activities of the antioxidant enzymes--catalase
      (CAT), total superoxide dismutase (SOD), and glutathione peroxidase (GPX)--were
      measured spectrophotometrically by decay of the substrate from the reaction
      mixture. The effect of IGF-1 on ROS levels in cultured human chondrocytes also
      was examined. In rat cartilage, FGF did not significantly affect ROS levels or
      antioxidant enzyme activity in any age group. TGF-beta1 significantly increased
      cellular ROS levels in mature and old cartilage whereas in marked contrast, IGF-1
      significantly and age-dependently reduced ROS levels. IGF-1 also had a potent
      antioxidant effect on cultured human chondrocytes. Pretreatment of rat cartilage
      with IGF-1 significantly enhanced the activity of GPX, without altering the
      activity of SOD or CAT, and protected chondrocytes against ROS-induced cell
      death. TGF-beta 1 had no significant effect on the activity of the antioxidant
      enzymes. Despite promoting ROS production, TGF-beta 1 was not cytotoxic. We
      concluded that TGF-beta 1 exhibits an acute pro-oxidant effect in cartilage that
      is not cytotoxic, suggesting a role in physiological cell signalling. In marked
      contrast, IGF-1 is a potent antioxidant in mature and aged rat and human
      chondrocytes, protecting cells against ROS-induced cell death probably through
      the enhancement of the activity of the antioxidant enzyme GPX.

PMID- 17522999
TI  - Keratinocyte apoptosis on type I collagen fibrils is prevented by Erk1/2
      activation under high calcium condition.
AB  - Keratinocytes adhere and proliferate well on collagen-coated surfaces, but they
      undergo apoptosis without differentiation on collagen gels according to our past
      research. In the current studies, we investigated the necessary conditions for
      keratinocyte survival on fibrous collagen gels. We found that keratinocytes
      survived on collagen gels when the medium contains elevated levels (1.8 mM) of
      calcium. Under this high calcium condition, cells formed multicellular colonies
      and differentiated. Akt was not activated in cells cultured on collagen gels
      regardless of the calcium concentration, whereas it was activated in cells
      cultured on nonfibrous collagen. On the other hand, Erk1/2, key kinases of MAPK
      pathway, were phosphorylated in cells cultured under high calcium condition but
      not in cells cultured on collagen gels under low calcium condition. The necessity
      of Erk1/2 activation for keratinocyte survival on collagen gel was confirmed with
      experiment using U0126, an inhibitor for Erk1/2. These studies show that
      activation of Akt depends on collagen assembly, whereas activation of Erk1/2 is
      induced by increased extracellular calcium concentration. Thus, activation of the
      Erk1/2 by increasing calcium concentration in the incubation medium may
      compensate for the loss of Akt activation, allowing keratinocyte survival on
      collagen gels.

PMID- 17523001
TI  - Evaluation of tablet formation of different lactoses by 3D modeling and fractal
      analysis.
AB  - The aim of this study was to use 3D modeling to differentiate not only among the
      four different types of lactose alpha-lactose monohydrate, spray-dried lactose,
      agglomerated lactose and lactose anhydrous but also between products from
      different manufacturers. Further "box-counting" fractal analysis of SEM images
      was done to gain additional information on tableting characteristics and tablet
      properties which can be found in the fractal structure. Twelve different
      materials from different manufacturers were analyzed for their powder
      technological and physicochemical properties. They were tableted on an eccentric
      tableting machine at graded maximum relative densities and the recorded data,
      namely force, time, and displacement were analyzed by the 3D modeling technique.
      Tablet properties such as, elastic recovery, crushing force and morphology were
      analyzed. The results show that 3D modeling can precisely distinguish deformation
      behavior for different types of lactose and also for the same type of material
      produced with a slightly different technique. Furthermore, the results showed
      that the amorphous content of the lactose determined the compactibility of the
      material, which is due to a reversible exceeding of the glass transition
      temperature of the material. The three fractal dimensions DBW (box surface
      dimension), DWBW (pore/void box mass dimension), and DBBW (box solid mass
      dimension) are capable of describing morphological differences in lactose
      materials. Multivariate regression analysis showed that the fractal surface
      structure of the lactose-based materials is strongly correlated to tableting
      characteristics and tablet properties. Especially with regards to 3D modeling, it
      was found that the fractal indices can describe the parameters time plasticity d,
      pressure plasticity e, and fast elastic decompression, which is the inverse of
      omega. In addition, the 3D parameters are able to describe the powder and tablet
      fractal indices. In conclusion, the 3D modeling is not only able to characterize
      the compression process but it can also provide information on the final tablet
      morphology.

PMID- 17523002
TI  - Simultaneous estradiol and levonorgestrel transdermal delivery from a 7-day
      patch: in vitro and in vivo drug deliveries of three formulations.
AB  - A new drug-in-adhesive transdermal patch was developed to deliver both estradiol
      and levonorgestrel through the skin over a 7-day period, but at different rates.
      This report elucidates the in vitro and in vivo biopharmaceutical studies that
      were necessary during the development of this product. Three test patches had to
      be manufactured, all delivering estradiol at the same rate, but delivering
      levonorgestrel at three different rates so that a levonorgestrel dose response
      could be studied in the clinic. An in vitro hairless mouse skin model (HMS) using
      modified Franz diffusion cells was used to select the test products delivering
      levonorgestrel in the order of 1:2:3. HMS experiments also demonstrated that the
      presence of estradiol did not affect the flux of levonorgestrel. Two in vivo
      studies in postmenopausal women showed that at steady state (four weeks of once
      weekly dosing) the three test products all delivered estradiol at comparable
      rates. Similarly, the levonorgestrel deliveries for the three test products were
      in the order expected. The target fluxes of both drugs were achieved in these
      three test products by varying the drug loads and patch size. That this approach
      was successful is evidence of the value of using the HMS penetration experiments
      in transdermal product development and should provide useful insights for other
      formulations having to develop complex systems. One of the test products is now
      marketed as Climara Pro.

PMID- 17523003
TI  - Porous carrier based floating granular delivery system of repaglinide.
AB  - A floating granular delivery system consisting of calcium silicate (CS) as porous
      carrier; repaglinide (Rg), an oral hypoglycemic agent; and hydroxypropyl
      methylcellulose K4M (HPMC K4M), ethyl cellulose (EC) and carbopol 940 (CP940) as
      matrix forming polymers was prepared and evaluated for its gastro-retentive and
      controlled release properties. The effect of various formulation and process
      variables on the particle morphology, micromeritic properties, in vitro floating
      behavior, drug content (%) and in vitro drug release was studied. The transit of
      floating granules of optimized formulation in the gastrointestinal (GI) tract was
      monitored by gamma scintigraphy in albino rabbits. The optimized formulation was
      compared in vivo with lactose granules (RgSCLG) prepared from identical polymers
      with their optimized composition ratio. Repaglinide-loaded optimized formulation
      was orally administered to albino rabbits and blood samples collected were used
      to determine pharmacokinetic parameters of Rg from floating granular formulation.
      Results were compared with pharmacokinetic parameters of marketed tablet
      formulation of Rg. The optimized formulation (RgSCG4) demonstrated favorable in
      vitro floating and release characteristics. Prolonged gastric residence time
      (GRT) of over 6 hr was achieved in all subjects for calcium silicate based
      floating granules of Rg. The relative bioavailability of Rg-loaded floating
      granules increased 3.8-fold in comparison to that of its marketed capsule. The
      designed system, combining excellent buoyant ability and suitable drug release
      pattern, offered clear advantages in terms of increased bioavailability of
      repaglinide.

PMID- 17523004
TI  - Storage conditions for stability testing of pharmaceuticals in hot and humid
      regions.
AB  - A review of the methodology for determination of the storage conditions for
      stability testing according to Schumacher/Grimm is presented in this paper. The
      purpose is to provide scientific information useful for the definition of storage
      conditions for stability testing of pharmaceuticals suitable to the region where
      the product will be dispensed. Special attention is given to stability testing in
      the new markets located in developing countries with very hot and humid climates.
      Finally, storage conditions for stability testing in the Brazilian regions were
      derived and examined comparatively with the guidelines of the world health
      organization (WHO) and regulatory bodies. The storage conditions were derived
      from the calculated values of the mean kinetic temperature and the relative
      humidity (RH). These parameters were estimated from daily values of dry and dew
      point temperatures of all Brazilian capitals from 1998 to 2002; collected in the
      morning (9 a.m.), in the afternoon (3 p.m.), and at night (9 p.m.). The Brazilian
      Center of Weather Forecast and Climatic Studies of the National Institute of
      Spatial Research (CPTEC/INPE) kindly furnished these data. Significant
      differences of the mean kinetic temperature (MKT) and relative humidity (RH) for
      Brazilian regions were observed. These results indicate the existence of a high
      climatic diversity between the Brazilian regions, making challenging the
      definition of a single storage condition for the stability testing. Some regions
      present RH values higher than 80%, giving support to the concerns of the WHO,
      indicating the necessity of revision of existing guidelines for stability testing
      mainly for very hot and humid regions.

PMID- 17523005
TI  - Formulation design of a highly hygroscopic drug (pyridostigmine bromide) for its
      hygroscopic character improvement and investigation of in vitro/in vivo
      dissolution properties.
AB  - Pyridostigmine bromide (PB) sustained-release (SR) pellets were developed by
      extrusion-spheronization and fluid-bed methods using Taguchi experimental and
      2(3) full factorial design. In vitro studies, the 2(3) full factorial design was
      utilized to search for the optimal SR pellets with specific release rate at
      different time intervals (release percent of 2, 6, 12, and 24 hr were 6.24,
      33.48, 75.18, and 95.26%, respectively) which followed a zero-order mechanism
      (n=0.93). The results of moisture absorption by Karl Fischer has shown the
      optimum SR pellets at 25 degrees C/60% RH, 30 degrees C/65% RH, and 40 degrees
      C/75% RH chambers from 1 hr-4 weeks, attributing that the moisture absorption was
      not significantly increased. In the in vivo study, the results of the
      bioavailability data showed the Tmax (from 0.65+/-0.082 hr-4.82+/-2.12 hr) and
      AUC0-30 hr (from 734.88+/-230.68 ng/mL.hr-1454.86+/-319.28 ng/mL.hr) were
      prolonged and increased, as well as Cmax (from 251.87+/-27.51 ng/mL-115.08+/
      14.87 ng/mL) was decreased for optimum SR-PB pellets when compared with
      commercial immediate-release (IR) tablets. Furthermore, a good linear regression
      relationship (r=0.9943) was observed between the fraction dissolution and
      fraction absorption for the optimum SR pellets. In this study, the formulation
      design not only improved the hygroscopic character of PB but also achieved the SR
      effect.

PMID- 17523006
TI  - In vitro measurements of mucoadhesive properties of six types of pectin.
AB  - The objective of this study was to measure and compare the specific- and general
      mucin interaction of six pectin types from three manufacturers, differing mainly
      in the degree of methoxylation and degree of amidation. Mucoadhesive properties
      were measured using a texture analyzer. It was found that an intermediate degree
      of methoxylation (35 and 36%) improved the specific mucin interaction. Amidation
      did not increase mucin interaction. Samples from different manufacturers did not
      alter these conclusions. This study indicates that the general classification of
      pectin as a poor mucoadhesive, without differentiating between the amount and
      type of substituents, probably is an oversimplification.

PMID- 17523007
TI  - Development and in vitro characterization of chitosan-based microspheres for
      nasal delivery of promethazine.
AB  - Conventional and composed promethazine-loaded microspheres were prepared by spray
      drying of chitosan solution systems and double water-in-oil-in-water (W/O/W)
      emulsion systems, respectively. Double emulsions were prepared in two different
      feed concentrations, with chitosan dissolved in both water phases, and
      ethylcellulose dissolved in oil phase. Swelling and bioadhesive properties of the
      microspheres depended on the chitosan content, type and the feed concentration of
      spray-dried system. Results obtained suggested that better ethylcellulose
      microcapsules with promethazine in the chitosan matrix were formed when less
      concentrated emulsion systems were spray-dried. Thus, in case of such a system,
      with ethylcellulose/chitosan weight ratio of 1:2, prolonged promethazine release
      was obtained.

PMID- 17523008
TI  - Potential mucoadhesive dosage form of lidocaine hydrochloride: II. In vitro and
      in vivo evaluation.
AB  - The aim of this study was to develop a controlled release buccal mucoadhesive
      delivery system for systemic delivery of lidocaine hydrochloride as a model drug.
      In vitro release and buccal permeation as well as in vivo permeation of LDHCL
      patches were evaluated. The drug release and the permeability of the drug through
      porcine buccal mucosa were evaluated using Franz diffusion cell. In vivo
      evaluation of patches was carried out on rabbits as an animal model. Patches were
      designed in two fashions, bi-layer (BLP; LDHCL, carbopol, glycerin, pentration
      enhancer, and Tween 20 as the first layer; and EVA as the second layer) and
      triple layer (TLP; LDHCL, carbopol and glycerin as the first layer; carbopol,
      glycerin, pentration enhancer and pluronic F-127 as the middle layer; and EVA as
      the third layer) patches, respectively. Presence of oleic acid as PE in the
      formulation significantly enhanced the in vitro permeability of LDHCL (p<0.05),
      while propylene glycol monolaurate as PE suppressed it (p<0.05). The in vivo
      evaluation in rabbits showed that TLP had significantly higher Cmax and AUC0-8
      (p<0.05) than BLP. Furthermore, TLP showed a well-controlled drug plasma
      concentration over 6 hr which was significantly longer than BLP (p<0.05). Patches
      were well adhered to buccal mucosa of the rabbits over the 8-hr study period. It
      was postulated that the hypothetical release mechanism of the drug and oleic acid
      from TLP was controlled by their diffusion through the swollen polymer network
      and micelled gel.

PMID- 17523009
TI  - Transport of insulin in modified Valia-Chien chambers and Caco-2 cell monolayers.
AB  - The transport characteristics of insulin were investigated using two different
      absorption models. Using the modified Valia-Chien chambers, permeability
      coefficients of insulin in the duodenum, jejunum, and ileum were 0.71x10(-7),
      7.11x10(-7) and 9.45x10(-7) cm/s, respectively. In the Caco-2 cell monolayers,
      the bidirectional transepithelial fluxes of insulin across Caco-2 cell line
      showed symmetry. Confocal laser scanning microscopy visualized that FD-4 and FITC
      insulin were mainly located in the paracellular route. It is evident that the
      lower intestine might be an advantageous region, and absorption enhancer that
      helps open tight junctions between cells should be used for oral delivery of
      insulin.

PMID- 17523010
TI  - Effect of neutralization of poly(methacrylic acid-co-ethyl acrylate) on drug
      release from enteric-coated pellets upon accelerated storage.
AB  - The effect of neutralization of poly(methacrylic acid-co-ethyl acrylate) or
      poly(MA-EA) 1:1 (Eudragit L 30 D-55) on drug release from enteric-coated pellets
      was studied upon accelerated storage. The dissolution rate of un-neutralized
      poly(MA-EA)-coated pellets decreased while the neutralized polymer-coated pellets
      maintained a constant drug release rate. Dynamic mechanical analysis showed that
      both un-neutralized and neutralized poly(MA-EA) films became rigid on aging.
      However, the un-neutralized films were affected more than those neutralized.
      Neutralization of poly(MA-EA) significantly changed the mechanical properties of
      coating films and improved the stability of poly(MA-EA) enteric-coated pellets
      upon accelerated storage at the studied conditions.

PMID- 17523011
TI  - Investigation of the biopharmaceutical behavior of theophylline hydrophilic
      matrix tablets using USP methods and an artificial digestive system.
AB  - This work aimed to investigate the biopharmaceutical behavior of hydrophilic
      matrix tablets of theophylline using different in vitro methods: USP II, USP IV,
      and a novel in vitro system simulating the gastrointestinal tract in man called
      the artificial digestive system (ADS). The potentiality of each method was
      evaluated by establishing in vitro/in vivo correlation. Using USP methods, the
      drug release was pH-independent and dependent on agitation intensity. Level A
      IVIVCs could be established using the different in vitro methods but one to one
      correlation was established only when the ADS method was used. For the prediction
      of in vivo drug dosage form behavior based on in vitro methods, the ADS showed a
      high predictability when compared to USP in vitro methods.

PMID- 17523012
TI  - Enhanced oral bioavailability of piroxicam in rats by hyaluronate microspheres.
AB  - To enhance the dissolution and oral bioavailability of poorly water soluble
      piroxicam, the piroxicam-loaded hyaluronic microspheres were prepared with
      various ratios of piroxicam, sodium hyaluronate and polyethylene glycol 4000
      (PEG) using a spray dryer, and their physicochemical properties such as shape,
      size, drug-loading efficiency and dissolution were investigated. The
      pharmacokinetic study of piroxicam-loaded hyaluronic micropheres in rats was then
      performed compared to piroxicam powder. The piroxicam-loaded hyaluronic
      microspheres, spherical in shape, had the geometric mean diameters of about 1.5
      microm and drug loading efficiency of about 90%, irrespective of ratio of
      piroxicam/sodium hyaluronate/PEG. The hyaluronic microspheres containing PEG gave
      significantly higher dissolution rates of drug than did piroxicam powder, PEG
      based solid dispersion system and hyaluronic microspheres without PEG, suggesting
      that the hyaluronic microsphere with sodium hyaluronate and PEG was more useful
      for improving the dissolution rate of poorly water soluble piroxicam. The
      piroxicam-loaded hyaluronic microcapsule composed of (piroxicam/sodium
      hyaluronate/PEG; 2: 20: 1) gave about threefold improved dissolution of drug in
      water for 4 h compared to piroxicam powder. It showed higher plasma
      concentrations of drug compared to piroxicam powder. It gave significantly higher
      AUC and faster Tmax of piroxicam than did piroxicam powder. In particular, the
      AUC of piroxicam from hyaluronic microsphere was about twofold higher than that
      from piroxicam powder, suggesting that it could enhance the oral bioavailability
      of piroxicam. Thus, the hyaluronic microsphere developed using spray-drying
      technique with sodium hyaluronate and PEG was a more effective oral dosage form
      for poorly water soluble piroxicam.

PMID- 17523016
TI  - Hyperthermia attenuates TNF-alpha-induced up regulation of endothelial cell
      adhesion molecules in human arterial endothelial cells.
AB  - BACKGROUND AND AIM: The activation of NF-kappaB induces production of
      inflammatory cytokines and up regulation of endothelial cell adhesion molecules
      (ECAM). ECAM (e.g., E-selectin, VCAM-1 and ICAM-1) associates to the recruitment
      of leukocytes into tissue exposed to inflammatory situation. In this study, we
      investigated the effects of hyperthermia on the activation of NF-kappaB and the
      up regulation of E-selectin and VCAM-1 in human endothelial cells stimulated by
      TNF-alpha. METHODS: Human arterial endothelial cells (HAEC) were pretreated with
      hyperthermia for 60 min at 42 degrees C, followed by incubation at 37 degrees C
      in a passively cooled incubator, before TNF-alpha stimulation. To assess the
      effects of hyperthermia on TNF-alpha-induced up regulation of ECAM and TNF-alpha
      induced activation of NF-kappaB, we measured ECAM by ELISA, and evaluated the
      activation of NF-kappaB by Western blotting after TNF-alpha stimulation. The
      accumulation of HO-1, Hsp70 and IkappaBalpha in hyperthermia-treated HAEC was
      also assessed by Western blotting. To investigate the role of Hsp70, we treated
      HAEC with geranylgeranylacetone (GGA, Hsp70 inducer) 2 h before hyperthermia, and
      then measured ECAM in TNF-alpha-stimulated HAEC by ELISA. RESULTS: Pretreatment
      of hyperthermia reduced TNF-alpha-induced up regulation of E-selectin and VCAM-1.
      In addition, accumulation of Hsp70, HO-1 and IkappaBalpha protein were up
      regulated after hyperthermia. Furthermore, Western blotting analysis revealed
      that pretreatment of hyperthermia attenuated TNF-alpha-induced translocation of
      p65 into the nuclei of HAEC. Moreover, GGA enhanced Hsp70 accumulation induced by
      hyperthermia. Hyperthermia pretreatment combined with GGA induced further
      inhibition of TNF-alpha-induced up regulation of ECAM when compared with
      hyperthermia alone. CONCLUSION: Pretreatment of hyperthermia blocks TNF-alpha
      induced NF-kappaB activation, resulting in the inhibition of ECAM up regulation
      in HAEC.

PMID- 17523017
TI  - Study of heat shock response of human umbilical vein endothelial cells (HUVECs)
      using cDNA microarray.
AB  - Genetic response of human umbilical vein cells (HUVECs) to heat shock was studied
      using gene expression analysis. HUVECs were subjected to heat treatment at 44
      degrees C and 55 degrees C for 1 h, respectively. Four hours after the treatment,
      gene expression of the treated cells and control cells (37 degrees C) were
      profiled using cDNA microarray. Data were analyzed using bioinformatics tools,
      and the results were verified by real-time quantitative PCR experiment. It has
      been shown that a large number of genes were regulated indicating global response
      to heat treatment at the genetic level.

PMID- 17523018
TI  - Whole body hyperthermia improves obesity-induced insulin resistance in diabetic
      mice.
AB  - AIM: In this study, we examined the efficacy of whole body hyperthermia (WBH) on
      obesity-induced insulin resistance in diabetic mice. METHODS: Male db/db mice
      were treated with WBH 3 times per week for 12 weeks. The rectal temperature of
      mice reached 38.0 degrees C 5 min after heating, and was kept at 38.0 degrees C
      for 30 min. At the end of each week, tail snip glucose levels were determined
      under fasting conditions. The GLUT-4 gene expression of muscle tissue was
      analyzed by real-time PCR. RESULTS: (1) WBH-treated db/db mice showed a
      significant decrease in fasting blood glucose level as compared with untreated
      db/db mice (p < 0.01). (2) Plasma insulin levels in untreated db/db mice at the
      age of 10 weeks were significantly increased compared with those of db/+ mice (p
      < 0.0001). On the other hand, the reduction (31%) in insulin levels in WBH
      treated mice indicated improved insulin sensitivity. (3) The ability of WBH to
      increase insulin sensitivity was further established in glucose tolerance tests
      and insulin tolerance tests. (4) Urine albumin of db/db mice significantly
      increased compared with those of db/+ mice at 18 weeks of age (p < 0.001). This
      increase in urinary albumin was significantly inhibited by WBH (p < 0.01). (5)
      WBH up-regulated the expression of GLUT4 mRNA in skeletal muscle. CONCLUSION:
      Although the mechanisms have not yet been completely investigated, WBH may
      provide a new therapeutic or preventive modality against obesity-related diseases
      such as T2DM and metabolic or insulin resistance syndrome.

PMID- 17523020
TI  - NF-kappaB regulates the response of embryonic cells to heat shock.
AB  - NF-kappaB was shown previously to regulate apoptotic cell death processes in
      various experimental systems. However, its role in controlling teratogen-induced
      cell death has not been established yet. Therefore, the objective of the present
      study was to explore the involvement of the p65 subunit of NF-kappaB in the
      response of mouse embryonic fibroblasts (MEFs) to heat shock, using p65 knockout
      (p65-/-) cells. Indeed, we found p65-/- MEFs to be more susceptible to the
      exposure to heat shock, as compared with wild-type (WT) MEFs, as they
      demonstrated a more prominent decrease in cell survival and proliferation as well
      as the appearance of cells undergoing apoptotic cell death. These heat-shock
      induced effects were preceded by a decrease in p65 expression in WT cells, which
      was accompanied by a decrease in IkappaBalpha expression in WT MEFs, while
      disappearing completely in p65-/- MEFs and accordingly, by an increase in p
      IkappaBalpha expression in both cell lines, which was found to be more prominent
      in p65-/- MEFs. Interestingly, the heat shock-induced decrease in p65 expression
      was accompanied by an increase in HSP70 expression in both cell lines. However,
      it was again found to be more prominent in p65-/- MEFs. Taken together, our
      results suggest a protective role for the p65 subunit of NF-kappaB in mechanisms
      underlying the response of embryonic cells to heat shock.

PMID- 17523019
TI  - Prediction of anti-tumour effect of thermochemotherapy with in vitro
      thermochemosensitivity testing for non-small cell lung cancer.
AB  - PURPOSE: We investigated whether it is possible to predict the antitumour effects
      of thermochemotherapy from the results of anticancer agent sensitivity testing.
      MATERIALS AND METHODS: We produced a nude mouse cancer model using 4 lung cancer
      cell lines. Animals were divided into 4 groups: Thermotherapy (HT group),
      chemotherapy (CT group), thermochemotherapy (HT+CT group), and no therapy (NT
      group). Comparison of in vivo and in vitro effects were performed using cisplatin
      (CDDP), doxorubicin (ADR) and vinorelbine (NVB). In vivo thermotherapy was
      performed using the Thermotron RF IV, and radiofrequency (RF) capacitative
      hyperthermia device that induces a localised temperature of 42.0 degrees C for 45
      min. The collagen gel embedded culture drug sensitivity test (CD-DST) was used
      for in vitro chemosensitivity analysis of the anticancer agents. In vitro
      thermochemotherapy was performed using a modified CD-DST method, with the
      incubator set at 42.0 degrees for the first hour of the 24 hours drug exposure
      period. RESULTS: A good correlation was seen between in vivo and in vitro
      treated/control ratios (T/C%) in the HT group (R = 0.91, p = 0.09). Good
      correlations were also seen between in vivo and in vitro T/C in all cell lines in
      the CT group (R = 0.759, p = 0.09) and the HT+CT group (R = 0.65, p = 0.02). True
      positive rate was 87.5% (7/8), and true negative rate was 100% (4/4).
      Sensitivity, specificity and accuracy were 100% (7/7), 80% (4/5), and 91.7%
      (11/12) respectively. CONCLUSION: A modified CD-DST using an exposure temperature
      of 42 degrees C can be used to predict the antitumour effect of
      thermochemotherapy.

PMID- 17523021
TI  - Delineation of potential hot spots for hyperthermia treatment planning
      optimisation.
AB  - The optimal feed parameters of the generators for a complex-phased hyperthermia
      array system consisting of 4, 8 or even more applicators cannot be found using
      only the expertise of the treatment staff or using the limited amount of field
      and temperature data obtained during treatment. A number of strategies have been
      proposed to help us with the task to optimise the hyperthermia treatment,
      including several strategies specifically addressing the occurrence of hot spots.
      Each of the latter strategies strongly relies on the specification of the
      potential hot spots. This specification is either based on anatomy or the
      selection of an arbitrary number of potential hot spots. Therefore it is not
      guaranteed that all potential hot spots are included. This paper introduces a
      procedure for the delineation and visualisation of potential (SAR) hot spots. The
      potential hot spots are delineated by selecting those points for which the
      maximal SAR exceeds a specific SAR selection level. This SAR selection level is
      defined relative to the highest achievable SAR in the target volume for a certain
      fixed heating power. A larger number of potential hot spots and hot spots of
      larger size are delineated if the selection level is decreased. Although the
      procedure still includes an arbitrary selection criterion, i.e. the selection
      level, the selection is solely based on calculated EM-field data. As a result all
      potential hot spots can be delineated a priori. Three different objective
      functions are applied to maximise the SAR in the target. The first only maximises
      the SAR in the target volume for a given system power output. The other two
      intrinsically set a constraint on the set of potential hot spots as a whole.
      Additionally the SAR in each delineated potential hot spot separately can be
      constrained. In two patient cases the SAR in potential hot spots can be kept
      below the selection value applied for delineation of the potential hot spots. If
      assessed in terms of constraining the SAR value below the selection level while
      maximising target heating efficiency the combination of an objective function
      only maximising the SAR in the target with a separate constraint on each
      potential hot spots appears to be the most efficient.

PMID- 17523022
TI  - On verification of hyperthermia treatment planning for cervical carcinoma
      patients.
AB  - PURPOSE: The aim of this study was to verify hyperthermia treatment planning
      calculations by means of measurements performed during hyperthermia treatments.
      The calculated specific absorption rate (SAR(calc)) was compared with clinically
      measured SAR values, during 11 treatments in seven cervical carcinoma patients.
      METHODS: Hyperthermia treatments were performed using the 70 MHz AMC-4 waveguide
      system. Temperatures were measured using multisensor thermocouple probes. One
      invasive thermometry catheter in the cervical tumour and two non-invasive
      catheters in the vagina were used. For optimal tissue contact and fixation of the
      catheters, a gynaecological tampon was inserted, moisturized with distilled water
      (4 treatments), or saline (6 treatments) for better thermal contact. During one
      treatment no tampon was used. At the start of treatment the temperature rise
      (DeltaT(meas)) after a short power pulse was measured, which is proportional to
      SAR(meas). The SAR(calc) along the catheter tracks was extracted from the
      calculated SAR distribution and compared with the DeltaT(meas)-profiles. RESULTS:
      The correlation between DeltaT(meas) and SAR(calc) was on average R = 0.56 +/-
      0.28, but appeared highly dependent on the wetness of the tampon (preferably with
      saline) and the tissue contact of the catheters. Correlations were strong (R
      approximately 0.85-0.93) when thermal contact was good, but much weaker (R
      approximately 0.14-0.48) for cases with poor thermal contact. CONCLUSION: Good
      correlations between measurements and calculations were found when tissue contact
      of the catheters was good. The main difficulties for accurate verification were
      of clinical nature, arising from improper use of the gynaecological tampon. Poor
      thermal contact between thermocouples and tissue caused measurement artefacts
      that were difficult to correlate with calculations.

PMID- 17523023
TI  - Morbidity and quality of life during thermotherapy using magnetic nanoparticles
      in locally recurrent prostate cancer: results of a prospective phase I trial.
AB  - PURPOSE: To investigate the treatment-related morbidity and quality of life (QoL)
      during thermotherapy using superparamagnetic nanoparticles in patients with
      locally recurrent prostate cancer. MATERIALS AND METHODS: Ten patients with
      biopsy-proven locally recurrent prostate cancer following primary therapy with
      curative intent and no detectable metastases were entered on a prospective phase
      I trial. Endpoints were feasibility, toxicity and QoL. Following intraprostatic
      injection of a nanoparticle dispersion, six thermal therapy sessions of 60 min
      duration were delivered at weekly intervals using an alternating magnetic field.
      National Cancer Institute (NCI) common toxicity criteria (CTC) and the European
      Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-PR25
      questionnaires were used to evaluate toxicity and QoL, respectively. In addition,
      prostate specific antigen (PSA) measurements were carried out. RESULTS: Maximum
      temperatures up to 55 degrees C were achieved in the prostates at 25-30% of the
      available magnetic field strength. Nanoparticle deposits were detectable in the
      prostates one year after thermal therapy. At a median follow-up of 17.5 months (3
      24), no systemic toxicity was observed. Acute urinary retention occurred in four
      patients with previous history of urethral stricture. Treatment-related morbidity
      was moderate and QoL was only temporarily impaired. Prostate-specific antigen
      (PSA) declines were observed in eight patients. CONCLUSIONS: Interstitial heating
      using magnetic nanoparticles was feasible and well tolerated in patients with
      locally recurrent prostate cancer. Deposition of nanoparticles in the prostate
      was highly durable. Further refinement of the technique is necessary to allow
      application of higher magnetic field strengths.

PMID- 17523027
TI  - Trauma and dissociation among prisoners.
AB  - The current study examined childhood abuse, dissociation and post-traumatic
      stress disorder (PTSD) among male prisoners. A sample of 101 randomly selected
      male prisoners was interviewed. The Dissociative Experiences Scale (DES),
      Childhood Abuse and Neglect Questionnaire (CANQ) and Structured Clinical
      Interview for DSM-IV (SCID-I)-PTSD module were applied. Probands reported high
      frequency of criterion A trauma (85.2%) and lifetime PTSD (66.4%). Also,
      dissociative experiences more frequent than that of general population and most
      frequent dissociative symptoms were amnesia and absorption. PTSD and childhood
      traumas occur at high rates in prisoners and this finding has implications for
      management and treatment.

PMID- 17523028
TI  - Child factors associated with parent involvement in usual clinical care of
      children and adolescents: a national register study.
AB  - The study examined the role of child level characteristics of age, gender,
      disorder and experience of family breakdown on parent involvement in the
      treatment of children and adolescents in a usual clinical care setting. Data from
      the national register of 20,856 children and adolescents treated in psychiatric
      hospitals and clinics in Norway in 2002 were analyzed using a three-level
      hierarchical model. Consultations attended by the child, mother and father were
      constructed as level 1, child characteristics as level 2 and clinics as level 3.
      Results indicated that 42% of the variance was explained by within-family
      differences of consultations and 56% by child characteristics. Only 2% of the
      variance was explained by clinic-to-clinic differences. In the total model, child
      factors of gender, disorder and family breakdown (but not age) were significant
      predictors of consultation with children and parents. Therapists should take into
      account the role of the gender, disorder and family breakdown in promoting parent
      involvement and hindering premature termination.

PMID- 17523029
TI  - Construct and discriminant validity and dimensionality of the Interview Schedule
      for Social Interaction (ISSI) in three psychiatric samples.
AB  - This study was aimed at investigating the psychometric properties of the
      Interview Schedule for Social Interaction (ISSI), in terms of construct and
      discriminant validity and unidimensionality, in three psychiatric samples with
      varying prerequisites for social interaction: 1) an outpatient sample of working
      age with mixed diagnoses, 2) an outpatient sample with schizophrenia, and 3) an
      inpatient sample composed of mentally ill, male offenders. The target constructs
      were psychosocial functioning and satisfaction in different life domains. It was
      hypothesized that the ISSI would mainly be related to psychosocial functioning
      and life domains characterized by social interaction, such as friends and family.
      A second hypothesis was that the ISSI ratings would discriminate between the
      three samples. The first hypothesis was confirmed, but the pattern of
      relationships was somewhat different between the groups. Whereas family contacts
      were of great importance for social integration in Samples 1 and 2, friends
      seemed more important for the mentally ill offenders. The second hypothesis was
      partly confirmed: three ISSI sub-scales out of four discriminated between the
      samples. Moreover, the ISSI proved to be a unidimensional construct. The support
      for the four proposed sub-scales was not unanimous, however, and the sub-scales
      targeting attachment constituted less stable factors. This study demonstrated the
      construct and discriminant validity of the ISSI when applied to samples with
      various mental disorders. The fact that similar results were obtained in all
      three samples, despite varying prerequisites for social interaction, strongly
      supports the validity of the ISSI. Providing the sub-scales are used with
      caution, the ISSI seems to be a reliable tool for use with patients with severe
      mental disorders.

PMID- 17523030
TI  - Diagnostic stability over 3 years in a total group of first-episode psychosis
      patients.
AB  - First-episode psychosis (FEP) patients are often given diagnoses that later have
      to be changed. The aim of this study was to measure the diagnostic stability in a
      total group of FEP patients; 146 FEP patients were followed longitudinally and
      prospectively. Their revised baseline diagnoses were compared with their 3-year
      follow-up diagnoses. The schizophrenic spectrum disorders showed a high
      diagnostic stability as a group, but there was a great flow of patients between
      the different schizophrenic spectrum diagnoses. Also schizophrenia was a stable
      diagnosis. The affective psychosis group was homogenous without interaction of
      other psychosis groups. The other psychosis diagnoses, both regarded as a group
      and individually, turned out to be quite heterogeneous, with low stability values
      and a split course, often ending up in the schizophrenic spectrum. Fifty one per
      cent did not fulfil the criteria for DSM-IV axis 1 psychosis diagnosis at follow
      up. In conclusion, our findings suggest that in the early phase of psychosis.
      Only three different diagnostic categories would be sufficient; "schizophrenic
      spectrum type", "affective psychosis," and for the rest "psychotic disorder NOS."

PMID- 17523031
TI  - Self-reported consumer satisfaction in mental health services: validation of a
      self-rating version of the UKU-Consumer Satisfaction Rating Scale.
AB  - The UKU-Consumer Satisfaction Rating Scale (UKU-ConSat) for the evaluation of
      consumer satisfaction in mental health services was constructed for assessments
      by independent professional interviewers. In the present study, a patient self
      reported version of the scale is validated against the original version. The
      Spearman's rank correlation between single items, subscores and the total of the
      original scale and the self-assessment version was found to be good. Another main
      finding was an acceptable unidimensionality of the self-rating version of the UKU
      Consumer Satisfaction rating scale, evaluated by a Mokken analysis. Furthermore,
      the internal consistency by Cronbach's alpha was found to be satisfactory. The
      results show that the patient self-rating version is psychometrically sound and
      therefore suitable for use in ordinary clinical practice. Being a part of a
      concept for continuous quality control and development in mental health services,
      the self-rating version of the UKU-ConSat promotes an open collaborative dialogue
      between professionals and users. A further advantage is that it saves
      professional time.

PMID- 17523032
TI  - Association between patients' gender, age and immigrant background and use of
      restraint--a 2-year retrospective study at a department of emergency psychiatry.
AB  - The study aimed to determine rates and types of patient restraint, and their
      relationship to age, gender and immigrant background. The study retrospectively
      examined routinely collected data and data from restraint protocols in a
      department of acute psychiatry over a 2-year period. Each patient is only counted
      once in this period, controlling for readmission. Of 960 admitted patients, 14%
      were exposed to the use of restraints. The rate was significantly higher among
      patients with immigrant background, especially in the younger age groups. Most
      commonly used were mechanical restraint alone for native-born patients and a
      combination of mechanical and pharmacological restraints for patients with
      immigrant background. The use of restraints decreased when patients reached 60
      years. Both patients' age and immigrant background seem to have an impact on the
      use of restraint.

PMID- 17523033
TI  - The role of life events in social phobia.
AB  - The aim was to investigate the relationship between life events and social
      phobia. An inventory assessing life events during childhood, adulthood as well as
      life events experienced in relation to the onset of the disorder was
      administrated to 30 subjects with a DSM-IV diagnosis of social phobia. They were
      recruited by announcement and diagnosed by the Structured Clinical Interview for
      DSM-IV for axes I and II disorders. Seventy-five controls were selected by
      matching age and gender from the local population register. Individuals with
      social phobia reported significantly more life events during childhood and more
      life events with negative impact during the social phobia debuting year.
      Conversely, they described fewer events in the adult life than the controls.
      Close relatives with disabling conditions in the childhood, conflicts with
      wife/husband/cohabitant and divorces or similar were significantly more common in
      the debuting year in social phobic group. In adult life, the healthy individuals
      described significantly more often increased authority at work. A gender-specific
      analysis revealed significantly more experiences of a death of a relative/close
      friend during the year before the social phobia debut and significantly more
      negative life events in the women's adult life. In summary, the present results
      support that life events have a role in social phobia that may be gender
      influenced.

PMID- 17523034
TI  - A systematic intervention to improve patient information routines and
      satisfaction in a psychiatric emergency unit.
AB  - Patients admitted to acute psychiatric hospitalization often report that they are
      being subject to coercion, irrespective of their official legal status. This
      experience may be related to a feeling of process exclusion and insufficient
      information about legal rights. Still, little systematic research has been
      performed to find effective ways of improving the quality of information
      presented to the patients and to increase patient satisfaction in a routine
      clinical setting. The purpose of our study was to systematically record measures
      of patient satisfaction before, during and after an intervention to improve the
      information procedures during patient admission. Based on a total of 763
      consecutive admissions in an emergency psychiatric ward, 433 completed patient
      questionnaires were returned, indicating measures of patient satisfaction and
      factual knowledge in 30 different questions. The patients' general satisfaction
      scores increased only slightly during and after the intervention, but a robust
      and sustained improvement of the patients' satisfaction with the information
      received was recorded. Furthermore, the patients also reported an increased
      knowledge about specific legal issues related to their hospitalization. As this
      is an important aspect of patients' rights, we advocate the use of systematic
      procedures to increase patients' awareness of their legal status and knowledge
      about procedures in connection with hospitalization.

PMID- 17523035
TI  - Somatization symptoms in young adult Finnish population--associations with sex,
      educational level and mental health.
AB  - We assessed somatization symptoms and their associations among a 31-year-old
      Finnish population sample (n=1598). Data on somatization symptoms were gathered
      from a review of all medical public outpatient records. Subjects with four or
      more somatization symptoms according to the DSM-III-R criteria were classified as
      somatizers. Ninety-seven (83 females) DSM-III-R somatizers (6.1%) were found.
      Somatization associated with female sex, lower educational level and increased
      psychiatric morbidity. Roughly half of the somatizers had a comorbid psychiatric
      disorder. Mood disorders did not associate specifically with somatization--in
      fact, after adjusting for sex and educational level only anxiety disorders and
      personality disorders associated with somatization. It may be concluded that it
      is important to recognize psychiatric disorders in subjects with somatization
      symptoms, especially as these symptoms have been shown to be treatable with both
      psychotherapy and psychiatric medication.

PMID- 17523036
TI  - The psychometric properties of the Swedish version of the Adolescent Drug Abuse
      Diagnosis (ADAD).
AB  - The psychometric properties of the Swedish version of the Adolescent Drug Abuse
      Diagnosis (ADAD) instrument were evaluated in two adolescent groups. The
      participants in the Normal group comprised 121 adolescents aged 15-17 years and
      the participants in the group of adolescents with antisocial problems comprised
      1168 youths aged 10-21 years detained under the Swedish Care of Young Persons Act
      in special youth homes. The ADAD instrument produced good interrater reliability;
      the subscales showed moderate internal consistency and concept validity was
      satisfactory and comparable with American and Swiss versions. Finally, the ADAD
      subscales produced meaningful correlations. The interviewer rating, the
      adolescent's rating and the composite scores are compared and discussed. The
      Swedish version of ADAD appears to be a psychometrically good instrument for
      assessing the severity of adolescent problems and their need for treatment.
      However, the composite scores need to be reconstructed to be useful in future
      research.

PMID- 17523037
TI  - Cerebrospinal fluid monoamine metabolites and suicide.

PMID- 17523038
TI  - Proceedings of the 11th annual meeting of the Bielschowsky Gesellschaft, 3rd
      joint meeting with the Berufsverband der Orthoptistinnen Deutschlands, Giessen,
      Germany, 18-20 November 2005.

PMID- 17523039
TI  - Reproducibility of visual acuity assessment in normal and low visual acuity.
AB  - PURPOSE: To assess the reproducibility of measurements of visual acuity in both
      the upper and lower range of visual acuity. MATERIALS AND METHODS: The
      retroilluminated ETDRS 1 and ETDRS 2 charts (Precision Vision) were used for
      measurement of visual acuity. Both charts use the same letters. The sequence of
      the charts followed a pseudorandomized protocol. The examination distance was 4.0
      m. When the visual acuity was below 0.16 or 0.03, then the examination distance
      was reduced to 1 m or 0.4 m, respectively, using an appropriate near correction.
      Visual acuity measurements obtained during the same session with both charts were
      compared. A total of 100 patients (age 8-90 years; median 60.5) with various eye
      disorders, including 39 with amblyopia due to strabismus, were tested in addition
      to 13 healthy volunteers (age 18-33 years; median 24). At least 3 out of 5
      optotypes per line had to be correctly identified to pass this line. Wrong
      answers were monitored. The interpolated logMAR score was calculated. In the
      patients, the eye with the lower visual acuity was assessed, and for the healthy
      subjects the right eye. Differences between ETDRS 1 and ETDRS 2-acuity were
      compared. RESULTS: The mean logMAR values for ETDRS 1 and ETDRS 2 were -0.17 and 
      0.14 in the healthy eyes and 0.55 and 0.57 in the entire group. The absolute
      difference between ETDRS 1 and ETDRS 2 was (mean +/- standard deviation) 0.051 +/
      0.04 for the healthy eyes and 0.063 +/- 0.05 in the entire group. In the acuity
      range below 0.1 (logMAR > 1.0), the absolute difference (mean +/- standard
      deviation) between ETDRS 1 and ETDRS 2 of 0.072 +/- 0.04 did not significantly
      exceed the mean absolute difference in healthy eyes (p = 0.17). Regression
      analysis (|ETDRS 1 - ETDRS 2| vs. ETDRS 1) showed a slight increase of the
      difference between the two values with lower visual acuity (p = 0.0505; r =
      0.18). DISCUSSION: Assuming correct measurement, the reproducibilty of visual
      acuity measurements in the lower acuity range is not significantly worse than in
      normals.

PMID- 17523040
TI  - Reaction test for competence in visual pathway lesions.
AB  - Performance in the visual environment was evaluated with a central fixation or a
      search target in 11 positions within 34 degrees on a CRT, superimposed on a
      landscape. Reaction times were recorded. We examined 24 patients aged 26-83, with
      lesions of the visual pathways and homonymous visual field defects, and 18 normal
      subjects aged 23-79. This simple test takes about 1 minute in normal subjects and
      four or more minutes in neurological patients. The test may be used to quantify
      saccadic adaptation to disability from homonymous field defects and to monitor
      the training effects of visual rehabilitation.

PMID- 17523041
TI  - Screening for refractive errors in preschool children with the vision screener.
AB  - BACKGROUND: The Vision Screener is a new, commercial version of the Power
      Refractor, an off-axis, hand-held video refractor to screen for amblyogenic
      refractive errors. The aim of our study was to determine the reproducibility of
      the measurements, compare them to cycloplegic refraction, and evaluate the
      sensitivity and specificity for the detection of amblyogenic refractive errors.
      PATIENTS AND METHODS: Included in the study were 161 preschool children, age 0.5
      7.2 years without manifest strabismus > 10 degrees , who attended the outpatient
      clinic. After three measurements with the Vision Screener (version 4.3.15) and
      one measurement with +3 dpt glasses, the child underwent cycloplegic refraction.
      RESULTS: The reproducibility of the three non-cycloplegic measurements was +/-
      0.5 dpt in 85% and +/- 1 dpt in more than 95% of the children. Accommodation
      reduced the manifest hyperopia that could be measured with the Vision Screener by
      up to 3 dpt in some children. Compliance with the +3 dpt glasses increased from
      20% in those under one year of age to > 75 % in those over three. The glasses did
      increase the sensitivity from 70% to 80% but decreased the specificity from 80%
      to 65%. CONCLUSION: The Vision Screener is easy to handle and gives reproducible
      results. The sensitivity and specificity are between 70 and 80%. The +3 dpt
      glasses are only helpful in a few patients. The latest software version with a
      new algorithm is now under evaluation.

PMID- 17523042
TI  - An automated method for creating simulated distorted images in amblyopic vision.
AB  - Spatial distortions in amblyopic vision can be captured by subjective reports or
      by a point-by-point mapping of the central part of the visual field. In this
      study, we developed a series of algorithms that provide a fine-grain mapping of
      the amblyopic percept. These algorithms can be applied to any real-world image.
      The images created based on these algorithms can be compared with the subjective
      percept of each amblyope.

PMID- 17523043
TI  - Resting positions of vergence and their relation to asthenopic complaints.
AB  - Dark vergence is a resting position of vergence, measured in a dark visual field
      to eliminate fusional, accommodative, and proximal stimuli. Dark vergence differs
      among subjects: the average subject converges to a viewing distance of about 1 m,
      while the inter-individual range is from infinity to about 40 cm. This paper
      reviews previous ergonomic studies on dark vergence in relation to asthenopic
      complaints that occur when working at near computer screens: subjects with
      distant dark vergence exert more convergence and experience stronger asthenopic
      complaints than subjects with near dark vergence. The dissociated phoria, a
      common clinical measure of resting vergence, is only weakly correlated with
      asthenopic complaints, probably because of accommodative influences that cause
      the difference between dark vergence and dissociated phoria.

PMID- 17523044
TI  - A pilot study for investigating cortical binocularity in humans using fMRI
      adaptation.
AB  - Disrupted stereovision is a feature that accompanies strabismus. This study uses
      an fMRI adaptation paradigm to assess the amount of cortical binocularity in
      subjects with normal or impaired stereopsis. We present data from a pilot study
      of two normally-sighted and one stereodeficient subject with alternating
      fixation. We adapted one eye to diagonally oriented sinusoidal gratings and
      tested either the same (monocular test) or the other eye (interocular transfer),
      using either the same or an orthogonal orientation. In normally-sighted subjects,
      we observed monocular adaptation but only weak interocular transfer in the
      striate cortex, whereas in the extrastriate cortex we found strong monocular as
      well as interocular adaptation. In the stereodeficient subject, monocular
      adaptation but no interocular transfer was obtained in the extrastriate cortex.
      These results suggest that impaired stereopsis is related to reduced interocular
      transfer of adaptation at higher levels of the cortical visual pathway.

PMID- 17523045
TI  - Reliability of three different visual acuity testing procedures in school
      children.
AB  - AIM: To evaluate the usability and reliability of three different visual acuity
      (VA) testing procedures using Landolt C's in 8 positions with a semi-automated
      computer program in school children. METHODS: 100 school children (median 7
      years, 59 boys and 41 girls) were included; only the better eye was tested. We
      used the semi-automated computer program CORVIS.VT in a forced choice method.
      Three different test strategies were employed, each two times: A) DIN, B)
      Standard-Staircase and C) Best-PEST procedure with sequences A, B, C or A, C, B.
      RESULTS: Average testing time was 100 s +/- 45 (DIN), 59 s +/- 36 (Staircase) and
      77 s +/- 25 (Best-PEST). The mean VA estimated with DIN was equivalent to that
      with the Best-PEST procedure. However, the mean VA with Standard-Staircase was
      one line less. In DIN, 76% of the retest scores were within 0.1 logMAR unit of
      the initial test score (Staircase: 72%, Best-PEST 73%). The 95% confidence
      interval of test-retest reliability was calculated to be -0.05 +/- 0.24 logMAR in
      DIN, +0.02 +/- 0.32 logMAR in Staircase, and 0.00 +/- 0.29 logMAR in Best-PEST.
      CONCLUSION: A high percentage of children aged 6 to 9 years (98%) can be tested
      with Landolt C's (8 positions). We found a decreasing test-retest reliability
      starting from DIN via Best-PEST to Staircase in this configuration.

PMID- 17523046
TI  - Spatial and temporal misperceptions in amblyopic vision.
AB  - The aim of this study was to investigate the spatial and temporal distortions
      that occur in strabismic and anisometropic amblyopic vision. Twelve subjects with
      strabismic (n = 4), anisometropic (n = 4), mixed amblyopia (n = 3) and bilateral
      refractive amblyopia (n = 1) were asked to describe and sketch their subjective
      percept of different geometrical patterns, as seen with their amblyopic eye.
      Based on their descriptions, computer-animated patterns were generated, which
      were then validated by the subjects. Both spatial distortions and temporal
      instability were perceived mainly by strabismic and strabismic-anisometropic
      amblyopes. Temporal instability occurred mainly at high spatial frequencies. Our
      data suggest that strabismus, in addition to amblyopia, is needed to elicit
      significant spatial and temporal distortions. The occurrence of these distortions
      may be related to the early history of each subject.

PMID- 17523047
TI  - Effects of unilateral ocular motor nerve palsies on smooth pursuit eye movements
      in adult patients.
AB  - AIM: The aim of this study was to investigate the influence of single ocular
      muscle weakness on smooth pursuit eye movements. METHODS: Infrared video
      recordings of horizontal and vertical eye movements were obtained from 14 adult
      patients with either unilateral abducens nerve palsy or trochlear nerve palsy.
      During the recordings, subsequent series of horizontal, vertical and oblique ramp
      stimuli of 10 degrees/s constant target velocity and +/-10 degrees amplitude were
      presented under monocular viewing conditions. RESULTS: In both forms of ocular
      nerve palsies, similar changes of pursuit eye movements were observed in the
      pulling plane of the paretic muscles. The movements of the covered paretic eye
      showed the lowest amplitude and gain values as well as the lowest numbers of
      catch-up saccades. The highest amplitude and gain values were calculated from the
      movements of the covered sound eye. The highest numbers of saccades, however,
      were produced by the fixating paretic eye. CONCLUSIONS: We conclude that the
      fixating paretic eye compensates for the paresis by raising the pursuit gain and
      the number of catch-up saccades. In the covered paretic eye, however, monocular
      adaptation is connected with a symmetric low pursuit gain and a reduced number of
      saccades in the pulling plane of the paretic muscle.

PMID- 17523048
TI  - The visual performance test: indications for compensational visual rehabilitation
      training and first results.
AB  - The visual performance test (Dannheim & Verlohr, 2007) measures the time required
      to find an object within the visual field. Black icons of high contrast are
      superimposed on a scenic background of low contrast in one of 11 positions in
      random order. The subject's task is to find the search icon on the CRT screen as
      rapidly as possible. This test was administered binocularly in 38 patients with
      homonymous visual field defects. The aim of the test was to identify those
      patients who had not adapted themselves to their visual handicap, and to quantify
      the effect, in these patients, of training of compensational search saccades
      (Meienberg et al., 1981; Nelles et al., 2001; Trauzettel-Klosinski, 2004). The
      results show that the visual performance test reflects the practical abilities of
      these patients and that it may monitor the benefit of visual rehabilitation
      training in patients with functional restrictions in daily life.

PMID- 17523050
TI  - Cytochrome P450 probe substrate metabolism kinetics in Sprague Dawley rats.
AB  - The objective of the current study was to investigate the metabolism of
      cytochrome P450 (CYP) probe substrates in male Sprague Dawley rat liver
      microsomes and to determine their substrate specificities. Time and microsomal
      protein concentrations were varied to determine the linear conditions for each
      reaction. Appropriate substrate concentrations were chosen to determine the
      apparent K(m) and V(max) for 17 different reactions under initial rate conditions
      of protein and reaction time. All reactions appeared to follow Michaelis-Menten
      kinetics. Subsequently, each substrate was incubated at one to two times K(m)
      with each of 14 baculovirus cDNA-expressed rat CYP enzymes to determine the
      specificity of the reaction monitored. Of the 14 enzymes tested, seven were seen
      as the major rat CYP enzymes responsible for the majority of the substrate
      metabolism tested. Testosterone 2alpha- and 16alpha-hydroxylation reactions were
      conducted primarily by CYP2C11, and midazolam 4-hydroxylation and triazolam 1'
      hydroxylation were preferentially catalyzed by CYP3A1/2, but specificity was
      otherwise generally poor. The results presented herein clearly indicate that care
      must be taken in interpretation of metabolism results obtained in rats using
      standard probe substrates, especially in extrapolation of those results to
      humans.

PMID- 17523051
TI  - Gemfibrozil and its glucuronide inhibit the hepatic uptake of pravastatin
      mediated by OATP1B1.
AB  - When pravastatin (40 mg/day) was co-administered with gemfibrozil (600 mg,
      b.i.d., 3 days) to man, the AUC of pravastatin increased approximately 2-fold. We
      have clarified that OATP1B1 is a key determinant of the hepatic uptake of
      pravastatin in humans. Thus, we hypothesized that gemfibrozil and the main plasma
      metabolites, a glucuronide (gem-glu) and a carboxylic acid metabolite (gem-M3),
      might inhibit the hepatic uptake of pravastatin and lead to the elevation of the
      plasma concentration of pravastatin. Gemfibrozil and gem-glu inhibited the uptake
      of (14)C-pravastatin by human hepatocytes with K(i) values of 31.7 microM and
      15.7 microM, respectively and also inhibited pravastatin uptake by OATP1B1
      expressing Xenopus laevis oocytes with K(i) values of 15.1 microM and 7.6 microM.
      Additionally, we examined the biliary transport of pravastatin and demonstrated
      that pravastatin was transported by MRP2 using both human canalicular membrane
      vesicles (hCMVs) and human MRP2-expressing vesicles. However, gemfibrozil, gem
      glu and gem-M3 did not affect the biliary transport of pravastatin by MRP2.
      Considering the plasma concentrations of gemfibrozil and gem-glu in humans, the
      inhibition of OATP1B1-mediated hepatic uptake of pravastatin by gem-glu would
      contribute, at least in part, to the elevation of plasma concentration of
      pravastatin by the concomitant use of gemfibrozil.

PMID- 17523052
TI  - Effect of enalapril on the in vitro and in vivo peptidyl cleavage of a potent VLA
      4 antagonist.
AB  - BIO1211 is a small peptidyl potent antagonist of the activated form of
      alpha4beta1 integrin. The effect of enalapril on the in vitro and in vivo
      cleavage of BIO1211 was investigated. In heparinized blood, plasma and rat liver,
      lung and intestinal homogenates, BIO1211 was converted rapidly to BIO1588 by
      hydrolytic cleavage of the terminal dipeptide moiety. This cleavage could be
      inhibited by EDTA and the ACE inhibitor, enalaprilat, the de-esterified acid
      derivative of enalapril. Enalaprilat inhibited the hydrolysis of BIO1211 in a
      concentration-dependent manner with IC(50) values of 2 nM in human and sheep
      plasma and 10 nM in rat plasma. In rat lung homogenate supernatant, the maximum
      inhibition of the conversion of BIO1211 to BIO1588 was approximately 80% at 1
      microM with no further effect up to 100 microM of enalaprilat. Following a
      concomitant IV administration of enalapril and BIO1211 at 3 mg/kg each, the AUC
      and the half-life values of BIO1211 increased 18- and 10-fold, respectively. The
      AUC of BIO1588 decreased approximately 2-fold with no change in its plasma half
      life. When rats were dosed intravenously with enalapril followed by an
      intratracheal dose of BIO1211, there was approximately 2.5-fold decrease in the
      AUC of BIO1588 and a 2.4-fold increase in its plasma half-life.

PMID- 17523053
TI  - Plasma pharmacokinetics and CYP3A12-dependent metabolism of c-kit inhibitor
      imatinib in dogs.
AB  - Imatinib is a highly selective tyrosine kinase inhibitor, and is used for the
      treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours
      (GISTs) in humans. The aim of this study is to determine the in vitro and in vivo
      pharmacokinetics of imatinib in dogs and which cytochrome P450 (CYPs) contribute
      to its metabolism. Imatinib was administered orally or intravenously to dogs and
      the time of the peak concentration (T(max)) of imatinib was 4-9 h. The mean half
      life was 622 +/- 368 min, and the AUC was 1256 +/- 809 microM * min after oral
      administration. The range of C0 of intravenously injected dogs was 12-24 microM.
      The half-life and AUC after intravenous injection were 206 +/- 112 min and 1026
      +/- 371 microM * min, respectively. Recombinant system of dog CYP3A12 and CYP2C21
      showed that CYP3A12 contributed to the metabolism of imatinib. The inhibition of
      CYP3A-dependent activity using a rat anti-CYP3A antibody or ketoconazole revealed
      that CYP3A12 plays a major role in the metabolism of imatinib in dog liver
      microsomes.

PMID- 17523054
TI  - The pharmacokinetics and disposition of MK-0524, a Prosglandin D2 Receptor 1
      antagonist, in rats, dogs and monkeys.
AB  - MK-0524 is a potent, selective and orally active Prosglandin D(2) Receptor 1
      (DP(1)) antagonist currently under clinical development for the treatment of
      niacin-induced flushing. Experiments to study the pharmacokinetics, metabolism
      and excretion of MK-0524 were conducted in rats, dogs and monkeys. MK-0524
      displayed linear kinetics and rapid absorption following an oral dose. Following
      intravenous (i.v.) administration of MK-0524 to rats and dogs (1 and 5 mg/kg),
      the mean Cl(p) was approximately 2 and approximately 6 ml/min/kg, the T(1/2) was
      approximately 7 and approximately 13 h and the Vd(ss) was approximately 1 and
      approximately 5 L/kg, respectively. In monkeys dosed i.v. at 3 mg/kg, the
      corresponding values were 8 ml/min/kg, 3 h and 1 L/kg, respectively. Following
      oral dosing of MK-0524 to rats (5, 25 and 100 mg/kg), dogs (5 mg/kg) and monkeys
      (3 mg/kg), the absorption was rapid with the mean C(max) occurring between 1 and
      4 h. Absolute oral bioavailability values in rats, dogs and monkeys were 50, 70
      and 8%, respectively. The major circulating metabolite was the acyl glucuronide
      of MK-0524 (M2), with ratios of glucuronide to the parent aglycone being highest
      in the monkey followed by dog and rat. In bile duct-cannulated rats and dogs, MK
      0524 was eliminated primarily via acyl glucuronidation followed by biliary
      excretion of the acyl glucuronide, M2, the major drug-related entity in bile.

PMID- 17523055
TI  - Disposition and metabolism of (2S,3S,4R)-N''-cyano-N-(6-amino-3,4-dihydro-3
      hydroxy-2-methyl-2-dimethoxy methyl-2H-benzopyran-4-yl)-N'-benzylguanidine, a
      novel neuroprotective agent for ischemia-reperfusion damage, in rats.
AB  - The metabolism and disposition of KR31378 (a benzopyran derivative and a novel
      neuroprotective agent) were investigated following single oral or intravenous
      administration of [(14)C]-KR31378 to rats. [(14)C]-KR31378 was rapidly absorbed
      after oral dosing with an oral bioavailability of greater than 71%. The maximum
      plasma concentration and area under the curve of total radioactivity in rat
      plasma increased proportionally to the administered dose. KR31378 was distributed
      over all organs and tissues except for brain, eyeball and testis, and declined by
      first order kinetics up to 24 h after dosing. Excretion of the radioactivity was
      29.5% of the dose in the urine and 58.5% in the feces within 2 days after oral
      administration. Biliary excretion of the radioactivity in bile duct-cannulated
      rats was about 66.0% for the first 24 h. KR31378 was extensively metabolized by
      ring hydroxylation, O-demethylation, oxidation and reduction with subsequent N
      acetylation and O-glucuronide conjugation. N-acetylated conjugates (M2, M10, M11,
      M12, M14, and M15) were identified as the predominant metabolites in rats.

PMID- 17523056
TI  - Disposition of sanguinarine in the rat.
AB  - Sanguinarine is an alkaloid with known antibiotic and anti-inflammatory activity
      and its pharmacokinetics have been studied in the rat after a single oral dose
      (10 mg kg(-1) body weight). Alkaloid determination in the plasma and liver was
      carried out by high-performance liquid chromatography-electrospray ionization
      mass spectrometry (HPLC/ESI-MS). The pharmacokinetic parameters (t(max), c(max),
      AUC(0-->t) and AUC(0-->infinity)) were determined for sanguinarine and
      dihydrosanguinarine, the major components detected in plasma. The first step in
      sanguinarine metabolism in the rat was the reduction of the iminium bond
      resulting in formation of the less toxic dihydrosanguinarine. Both compounds were
      completely eliminated from the plasma and liver after 24 h and not detected in
      urine. After a single oral dose of (3)H-sanguinarine, more than 42% of the
      ingested radioactivity was present in gastrointestinal tract. Benz[c]acridine, up
      to date the only sanguinarine metabolite referred to in the literature, was not
      detected in the plasma, liver or urine.

PMID- 17523063
TI  - [Surgical 4-year followup of a patient with lung transplantation].

PMID- 17523057
TI  - Metabolism and excretion of CP-122,721, a non-peptide antagonist of the
      neurokinin NK1 receptor, in dogs: identification of the novel cleaved product 5
      trifluoromethoxy salicylic acid in plasma.
AB  - The metabolism and excretion of a potent and selective substance P receptor
      antagonist, CP-122,721, have been studied in beagle dogs following oral
      administration of a single 5 mg kg(-1) dose of [(14)C]CP-122,721. Total recovery
      of the administered dose was on average 89% for male dogs and 95% for female
      dogs. Approximately 94% of the radioactivity recovered in urine and feces was
      excreted in the first 72 h. Male bile duct-cannulated dogs excreted a mean of
      approximately 56% of the dose in bile, approximately 11% in feces, and
      approximately 25% in urine. The sum of radioactivity in bile and urine indicates
      >80% of the [(14)C]CP-122,721-derived radioactivity was absorbed by the
      gastrointestinal tract. CP-122,721 was extensively metabolized in dogs, and only
      a small amount of parent CP-122,721 was excreted as unchanged drug. There were no
      significant gender-related quantitative/qualitative differences in the excretion
      of metabolites in urine or feces. The major metabolic pathways of CP-122,721 were
      O-demethylation, aromatic hydroxylation, and indirect glucuronidation. The minor
      metabolic pathways included: Aliphatic oxidation at the piperidine moiety, O
      dealkylation of the trifluoromethoxy group, and N-dealkylation with subsequent
      sulfation and/or oxidative deamination. In addition, the novel cleaved product 5
      trifluoromethoxy salicylic acid (TFMSA) was identified in plasma. These results
      suggest that dog is the most relevant animal species in which the metabolism of
      CP-122,721 can be studied for extrapolating the results to humans.

PMID- 17523068
TI  - [Locus of control belief is a predictor of CPAP-compliance in patients with
      obstructive sleep apnea syndrome].
AB  - Approximately 25 % of all patients suffering from obstructive sleep apnea
      syndrome (OSAS) discontinue CPAP-therapy in long-term follow-up. This study was
      conducted to investigate if there are any predictors signaling low compliance
      prior to initiation of CPAP-therapy. We used an open label longitudinal cohort
      study at an University hospital in-patient Sleep laboratory setting. In 85
      consecutive patients with a diagnosis of OSAS confirmed by polysomnography a CPAP
      therapy was initiated. Prior to CPAP-titration the subjects were interviewed
      using standardized, validated questionnaires (Nottingham Health Profile, von
      Zerssen's Depression Scale, State Trait Anxiety Inventory, IPC-Scale). On follow
      up (mean 16 +/- 8 month) 66 patients were still using CPAP regularly, 19
      individuals had discontinued the therapy. Data of both groups were compared.
      There were no significant differences in polysomnographic parameters before CPAP
      except apnea-hypopnea-index (users: 30.72 +/- 20.68, rejecters: 18.43 +/- 10.43)
      and mean oxygen saturation (users: 91.65 +/- 3.32, rejecters 93.63 +/- 1.86).
      Depression and anxiety levels were normal in both groups. The subjects who
      discontinued CPAP had a significantly less external control belief. Internal
      control belief was normal in all patients. It is suggested that individuals who
      discontinued CPAP could not be convinced of the necessity of CPAP by physicians
      or nurses due to their reduced external control belief. Identifying patients with
      diminished external control belief prior to prescription of a device might be
      useful. In selected subgroups, different methods of motivation to maintain long
      term acceptance for CPAP-therapy seems to be necessary.

PMID- 17523069
TI  - [Historical aspects on CPET (cardio pulmonary exercise testing)].

PMID- 17523070
TI  - [Global Initiative for Asthma Management and Prevention--GINA 2006].
AB  - GINA together with many other national guidelines for the clinical management of
      asthma recommend a disease severity assessment in order to determine the quantity
      and frequency of medication. This classification scheme groups patients into one
      of four categories (intermittent, mild-persistent, moderate-persistent, and
      severe-persistent). However, it is important to recognise that asthma severity
      includes both severity of the underlying disease and responsiveness to treatment.
      In addition, severity is not an unvarying feature in any individual asthma
      patient and disease severity may change over months or years. Thus, for ongoing
      asthma management, classification using the level of control may be more relevant
      and useful in clinical practice. The new version of the GINA guidelines 2006
      recognises these limitations of severity assessment and classifies the condition
      according to the level of control as "controlled", "partly controlled", and
      "uncontrolled" asthma on the basis of daytime symptoms, restrictions of physical
      activity, nocturnal symptoms/awakening, need for reliever/rescue medication, lung
      function (PEF or FEV1) and the frequency of exacerbations. In addition, the
      patient is assigned to one of five treatment "steps". Each step represents
      treatment options that are alternatives for controlling asthma. Moreover, steps 1
      to 5 provide options of increasing efficacy. In order to maintain asthma control
      regular monitoring and adjustment is essential. In cases where asthma is not or
      only partially controlled with the current treatment regimen, step-up treatment
      is recommended whereas disease control allows a gradual stepping-down to the
      lowest possible dose of medication necessary to maintain control. This novel
      asthma management approach based on disease control, may facilitate acceptance
      and use of asthma guidelines in clinical practice.

PMID- 17523071
TI  - [Extrinsic allergic alveolitis/hypersensitivity pneumonitis].

PMID- 17523072
TI  - Causal probabilistic modeling for malignancy grading in pathology with
      explanations of dependency to the related histological features.
AB  - This work demonstrates that histological grading of brain tumors and astrocytomas
      can be accurately predicted and causally explained with the help of causal
      probabilistic models, also known as Bayesian networks (BN). Although created
      statistically, this allows individual identification of the grade of malignancy
      as an internal cause that has enabled the development of the histological
      features to their observed state. The BN models are built from data representing
      794 cases of astrocytomas with their malignant grading and corresponding
      histological features. The computerized learning process is improved when pre
      specified knowledge (from the pathologist) about simple dependency relations to
      the histological features is taken into account. We use the BN models for both
      grading and causal analysis. In addition, the BN models provide a causal
      explanation of dependency between the histological features and the grading. This
      can offer the biggest potential for choice of an efficient treatment, since it
      concentrates on the malignancy grade as the cause of pathological observations.
      The causal analysis shows that all ten histological features are important for
      the grading. The histological features are causally ordered, implying that
      features of first order are of higher priority, e.g. for the choice of treatment
      in order not to allow the malignancy to progress to a higher degree. Due to the
      explanations of feature relations, the causal analysis can be considered as a
      powerful complement to any malignancy classification tool and allows reproducible
      comparison of malignancy grading.

PMID- 17523073
TI  - Prenatal corticosterone influences the trajectory of neuronal development,
      delaying or accelerating aspects of the Purkinje cell differentiation.
AB  - The nervous system developmental programs proceed in orderly fashion following
      strict timetables. However, the mechanisms regulating developmental timing remain
      largely unknown. Increases or decreases in glucocorticoids in the fetal brain can
      be detrimental. We present evidence supporting that corticosterone forwards the
      migration of cerebellar granule neurons when applied acutely during pregnancy.
      This change in developmental tempo enhances dendritic growth of Purkinje neurons,
      increases the nuclear area, accelerates perinucleolar rosette appearance and
      decreases the development of Nissl bodies. Our observations thus support that
      forwarding the occurrence of developmental events does not always arrest neuronal
      growth, as some heterochronic developmental models imply. We suggest that
      prenatal glucocorticoids alter the trajectory of Purkinje neurons development
      soon after birth. These changes could represent a transient condition or could
      produce medium or long-term later consequences. More studies are needed to
      evaluate these intriguing possibilities.

PMID- 17523074
TI  - Beta-galactosidase staining on bone marrow. The osteoclast pitfall.
AB  - The enzyme beta-galactosidase, encoded by the bacterial gene lac-Z, is commonly
      used as a histochemical reporter to track transplanted cells in vivo or to
      analyze temporospatial gene expression patterns by coupling expression of
      specific target genes to beta-galactosidase activity. Previously, endogenous beta
      galactosidase activity has been recognized as a confounding factor in the study
      of different soft tissues, but there is no description of the typical background
      on bone marrow sections when using the chromogenic substrate 5-Bromo-4-chloro-3
      indolyl beta-D-Galactoside (X-Gal). In this report, we show that osteoclasts in
      bone marrow sections specifically and robustly stain blue with X-Gal. This leads
      to a typical background when bone marrow is examined that is present from the
      first day post partum throughout the adult life of experimental mice and can be
      confused with transgenic, bacterial beta-galactosidase expressing hematopoietic
      or stromal cells. Experimental variations in the X-Gal staining procedure, such
      as pH and time of exposure to substrate, were not sufficient to avoid this
      background. Therefore, these data demonstrate the need for strenuous controls
      when evaluating beta-galactosidase positive bone marrow cells. Verifiable
      bacterial beta-galactosidase positive bone marrow cells should be further
      identified using immunohistological or other approaches. Specifically, beta
      galactosidase positive hematopoietic or stromal cells should be proven
      specifically not to be osteoclasts by co-staining or staining adjacent sections
      for specific markers of hematopoietic and stromal cells.

PMID- 17523075
TI  - Trichloroethylene exposure elicits damage in epididymal epithelium and
      spermatozoa in mice.
AB  - We have investigated the toxic effects of trichloroethylene (TCE) on the
      epididymis and epididymal sperm in mice. Mice were exposed to TCE (1000 ppm) by
      inhalation for 6 h/day for 5 days/week for 1 to 4 weeks. Segments of the
      epididymis (caput, corpus and cauda) were examined by light and electron
      microscopy. At the light microscopic level, degeneration and sloughing of
      epithelial cells were evident as early as 1 week after TCE exposure, and were
      most pronounced after 4 weeks. Such epithelial damage was observed in the caput,
      corpus and cauda regions of the epididymis. Ultrastructural observations revealed
      vesiculation in the cytoplasm, disintegration of basolateral cell membranes, and
      sloughing of epithelial cells. Sperm were found in situ in the cytoplasm of
      degenerated epididymal cells. Additionally, a large number of sperm in the
      epididymal lumen exhibited abnormalities including malformation of head and tail
      components. Our results demonstrated that exposure to TCE by inhalation causes
      damage to the epididymal epithelium and sperm.

PMID- 17523076
TI  - Expression pattern of squamous cell carcinoma antigen in oesophageal dysplasia
      and squamous cell carcinoma.
AB  - The aim of the present study was to evaluate the tissue expression of squamous
      cell carcinoma antigen (SCCA) in oesophageal dysplasia and squamous cell
      carcinoma (SCC) with reference to its clinico-pathologic and prognostic
      significance. Immunohistochemistry using SCCA polyclonal antibody was performed
      on SCCs from 61 surgical oesophagectomies. Fifteen cases of low-grade dysplasia
      (LGD) and 37 non-coexistent high-grade dysplasia (HGD) were also sampled from
      these materials, together with sixteen chronic cases of oesophagitis. SCCA
      immunoreactivity was present in the maturative compartments of all normal
      epithelia and oesophagitis. LGDs showed no SCCA immunoreactivity in the
      dysplastic proliferative component but only in the superficial normal layers. In
      94.6% of HGDs, no SCCA immunoreactivity was detected throughout the thickness of
      the epithelium. In SCCs, SCCA expression higher than 25% was found in 54% of
      cases. SCCA positivity showed an inverse correlation with histological grade,
      whereas no statistically significant correlation was found with TNM
      classifications, stage, or survival. SCCA is not expressed in early oesophageal
      carcinogenesis but, in SCC, it represents an indicator of histologic
      differentiation. In differentiated SCC, SCCA may represent a negative factor for
      cancer invasiveness, through inhibition of proteases.

PMID- 17523077
TI  - The role of conjunctival epithelial cell xanthine oxidoreductase/xanthine oxidase
      in oxidative reactions on the ocular surface of dry eye patients with Sjogren's
      syndrome.
AB  - Previous papers examined lipid peroxidase levels and myeloperoxidase activity as
      products of oxidative and inflammatory reactions in the tear fluid of patients
      suffering from dry eye. The aim of the present paper was to investigate whether
      the enzymes xanthine oxidoreductase/xanthine oxidase known to generate reactive
      oxygen species contribute to oxidative reactions on the ocular surface. Xanthine
      oxidoreductase/xanthine oxidase were examined immunohistochemically as well as
      histochemically in conjunctival epithelial cells of patients suffering from dry
      eye. Patients with verified autoimmune dry eye (Sjogren's syndrome) participated
      in our study; normal eyes served as controls. Conjunctival epithelial cells were
      obtained by the method of impression cytology using Millicell membranes. The
      results revealed a pronounced expression, as well as activity of xanthine
      oxidoreductase/xanthine oxidase in the conjunctival epithelium of dry eye. It is
      suggested that reactive oxygen species which are generated by this enzymatic
      system, contribute to oxidative reactions on the eye surface of patients with
      ocular manifestations of autoimmune disease (Sjogren's syndrome).

PMID- 17523078
TI  - Frequent intra-tumoural heterogeneity of promoter hypermethylation in malignant
      melanoma.
AB  - To investigate intra-tumoural coexistence and heterogeneity of aberrant promoter
      hypermethylation of different tumour suppressor genes in melanoma, we analyzed
      the intra-tumoural distribution of promoter methylation of RASSF1A, p16, DAPK,
      MGMT, and Rb in 339 assays of 34 tumours (15 melanoma primaries, 19 metastases)
      by methylation-specific PCR, correlation to histopathology and RASSF1A
      expression. We detected promoter hypermethylation of at least one gene in 74% of
      tumours (30%, 52%, 33%, 20%, and 40% for RASSF1A, p16, DAPK, MGMT and Rb,
      respectively). 70% of the cases exhibited an inhomogeneous methylation pattern
      (17%, 45%, 33%, 20%, and 40% for RASSF1A, p16, DAPK, MGMT and Rb, respectively).
      Samples from the core of the tumours represented the methylation state of the
      whole tumours more accurately than the periphery. Local intra-tumoural
      correlation was found between the promoter hypermethylation state of p16 and Rb
      or p16 and DAPK, or epitheloid tumour cell type and RASSF1A or p16 methylation.
      Mitosis rate and sex was correlated with methylation of RASSF1A. Histological
      results confirmed that promoter hypermethylation of RASSF1A led to aberrant
      expression patterns. We conclude that intra-tumoural inhomogeneity of promoter
      hypermethylation is frequent in melanoma and this supports the hypothesis of
      clonal instability during progression of melanomas. In prognosis studies, missing
      the intra-tumoural sample representativeness may result in a reduction of the
      sensitivities or specificities.

PMID- 17523079
TI  - Altered expression of urokinase-type plasminogen activator and plasminogen
      activator inhibitor in high-risk soft tissue sarcomas.
AB  - In recent years, classification of soft-tissue sarcomas (STS) has improved with
      cytogenetic analyses, but their clinical behavior is still not easily
      predictable. The aim of this study was to detect alterations in the urokinase
      type plasminogen system, involved in tumor growth and invasion, by comparing mRNA
      levels of its components with those of paired normal tissues, and relating them
      with patient clinical course. Real-time PCR was performed on human STS cell lines
      and tissues from highly malignant STS, including leiomyosarcomas and malignant
      fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen
      activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI
      1). Immunohistochemistry of gene products was also performed. Median mRNA values
      of all genes studied were higher in tumors than in paired normal tissues. In
      agreement with data on STS cell lines, significant up-regulation for uPA and PAI
      1 genes compared to reference values was seen. Moreover, different levels of
      expression were related to histotype and metastatic phenotype. There was
      accordance between uPA mRNA and protein expression, while immunodetection of PAI
      1 product was weak and scattered. Clearly, the controversial role of PAI-1
      protein requires further biological analyses, but evident involvement of uPA/PAI
      1 gene overexpression in STS malignancy may highlight a molecular defect useful
      in discriminating STS high-risk patients.

PMID- 17523080
TI  - The S100 proteins for screening and prognostic grading of bladder cancer.
AB  - The S100 gene family, which is composed of at least 24 members carrying the Ca2+
      binding EF-hand motif, has been implicated in both intracellular and
      extracellular functions, including enzyme activities, immune responses,
      cytoskeleton dynamics, Ca2+ homeostasis, cell growth and cell differentiation.
      Altered S100 protein levels are associated with a broad range of diseases,
      including cardiomyopathy, inflammatory and immune disorders, neurodegenerative
      disorders and cancer. Although the precise role of S100 protein in carcinogenesis
      is poorly understood, it seems that formation of homo- and hetero-dimers, binding
      of Ca2+ and interaction with effector molecules are essential for the development
      and progression of many cancers. Several studies have suggested that S100
      proteins promote cancer progression and metastasis through cell survival and
      apoptosis pathways. In animal models of bladder cancer, several S100 proteins are
      differentially expressed in bladder tumors relative to normal urothelium. In
      human bladder cancer, overexpression of S100A4, S100A8 or S100A11 are associated
      with stage progression, invasion, metastasis and poor survival. This review
      summarizes these findings and evaluates their implications for human bladder
      cancer management.

PMID- 17523081
TI  - Intervertebral disc biology, degeneration and novel tissue engineering and
      regenerative medicine therapies.
AB  - Degeneration of the intervertebral disc (IVD) is a major cause of low back pain
      affecting a large percentage of the population at some point in their lives.
      Consequently IVD degeneration and its associated low back pain has a huge socio
      economic impact and places a burden on health services world-wide. Current
      treatments remove the symptoms without treating the underlying problem and can
      result in reoccurrence in the same or adjacent discs. Tissue engineering offers
      hope that new therapies can be developed which can regenerate the IVD. Combined
      with this, development of novel biomaterials and an increased understanding of
      mesenchymal stem cell and IVD cell biology mean that tissue engineering of the
      IVD may soon become a reality. However for any regenerative medicine approach to
      be successful there must first be an understanding of the biology of the tissue
      and the pathophysiology of the disease process. This review covers these key
      areas and gives an overview of the recent developments in the fields of
      biomaterials, cell biology and tissue engineering of the IVD.

PMID- 17523082
TI  - Prostate stem cells and cancer.
AB  - Properties shared by neoplastic and stem cells indicate a possibility that
      somatic stem cells or transit-amplifying cells that have reacquired stem cell
      properties, particularly the ability for self-renewal, represent favorable
      targets for malignant transformation. In this review we discuss significance of
      the stem cell model for understanding prostate cancer pathogenesis and describe
      relevant studies in animals. It is proposed that dissemination of rare cancer
      stem cells may lead to metastatic disease and that resistance of such cells to
      multiple drugs and androgen ablation make them responsible for failure of current
      treatments. Thus further understanding of the cancer stem cell biology is needed
      for development of efficient rationally designed therapy permitting better
      targeting and better treatment outcomes for patients with prostate neoplasms.

PMID- 17523083
TI  - The function of actin in gene transcription.
AB  - Recent developments in the field of gene transcription regulation have unfolded a
      key role for actin as an important co-factor for all three eukaryotic RNA
      polymerases. In this review article we discuss the latest findings on actin in
      transcription of protein-coding and ribosomal genes, in complex with specific
      hnRNP proteins and a form of myosin 1beta which is entirely localized to the cell
      nucleus. Based on these recent studies, we propose a general model where actin
      may function in basal gene transcription as an allosteric regulator, to recruit
      transcriptional co-activators on active genes. A future challenge will be the
      identification of the polymerization state of actin in gene transcription and how
      it is mechanistically regulated.

PMID- 17523084
TI  - Use of corrected calcium in place of measured total calcium.

PMID- 17523085
TI  - Screening a novel class of anticoagulants for multi-organ toxicity using Fischer
      344 rats: involvement of clinical and anatomic pathologists in the early drug
      development process.
AB  - BACKGROUND: Veterinary clinical and anatomic pathologists play a critical role in
      assessing the safety of new molecules. The process for evaluation of candidate
      molecules in drug discovery may vary markedly, depending on the unique
      characteristics of the compound class. OBJECTIVES: The goal of this report is to
      describe the evaluation process for assessing the potential toxicity of 2
      anticoagulant compounds that were representative of molecules tested in early
      screening studies in Fisher rats, and to use these studies as an example of the
      strategic approach used by veterinary pathologists in pharmaceutical safety
      assessment. METHODS: Groups of 3 rats were given vehicle alone or one of several
      doses of compound A or B by oral gavage daily for 4 consecutive days. Survival;
      clinical signs; body and organ weight measurements; hematologic, coagulation, and
      clinical biochemical testing; and gross and histologic findings at necropsy were
      assessed. Transmission electron microscopy was used to characterize unique
      findings in the liver of rats treated with compound B. RESULTS: Both compounds
      caused dose-dependent prolongation of the prothrombin time (PT), activated
      partial thromboplastin time (APTT), and thrombin clotting time (TCT).
      Hepatobiliary and intestinal toxicity were identified by alterations in serum
      chemistry data, and by histopathologic findings. Electron microscopy and tissue
      inorganic phosphorus analysis revealed phospholipidosis in rats treated with
      compound B. CONCLUSIONS: Pharmacologically mediated or "on target" effects for
      these molecules were characterized by dose-progressive prolongation of the PT,
      APTT, and TCT. Nonpharmacologically mediated or "off-target" toxicity consisted
      of hepatoxicity and enterotoxicity. These liabilities required that scientists
      alter the original molecular scaffold to reach the desired therapeutic target and
      minimize toxicity.

PMID- 17523086
TI  - Plasma L-carnitine concentration in healthy dogs and dogs with hepatopathy.
AB  - BACKGROUND: L-Carnitine has an essential role in lipid metabolism. Disturbances
      of L-carnitine metabolism can influence the energy supply of the organism. L
      Carnitine is synthesized exclusively in the liver. Hence, we hypothesized that
      liver disease can influence L-carnitine metabolism. OBJECTIVES: The goal of this
      study was to compare plasma L-carnitine concentrations in dogs with different
      liver diseases of differing severity with the plasma L-carnitine concentrations
      of healthy dogs. METHODS: Sixteen dogs with inflammatory liver disease and 12
      dogs with liver neoplasia were included in the study. Liver disease was diagnosed
      by clinical chemistry, ultrasonography, and histology of liver biopsy specimens.
      L-Carnitine concentration was measured in plasma samples using mass spectrometry,
      and compared among groups using unpaired Student's t-tests. RESULTS: Compared
      with healthy controls (24.4 +/- 8.4 micromol/L), the plasma L-carnitine
      concentration in dogs with liver disease (44.2 +/- 23.7 micromol/L) was
      significantly higher (P<.0001). The difference in L-carnitine concentration
      between dogs with moderate (n=8; 33.6 +/- 13.7 micromol/L) and severe (n=8; 57.4
      +/- 22.9 micromol/L) hepatitis was also significant (P=.02). No difference in
      plasma L-carnitine concentration was found between dogs with hepatitis and those
      with liver tumors. CONCLUSIONS: Liver disease in dogs was accompanied by elevated
      plasma L-carnitine concentration. The severity of hepatitis appears to influence
      L-carnitine concentration.

PMID- 17523087
TI  - An update on FIV and FeLV test performance using a Bayesian statistical approach.
AB  - BACKGROUND: Screening tests for feline retroviruses are thought to have high
      sensitivity and specificity, although previous studies that evaluated these tests
      have limitations. Novel statistical approaches have been developed that allow the
      estimation of sensitivity and specificity in situations where the true state of
      the disease in individual animals cannot be assured. OBJECTIVE: The purpose of
      this study was to evaluate the sensitivity and specificity of a variety of
      retrovirus tests, including some screening tests, in a population of cats
      potentially infected with either feline leukemia virus (FeLV) and/or feline
      immunodeficiency virus (FIV) by using a Bayesian statistical approach. METHODS:
      Four hundred and ninety blood samples from cats being evaluated for FIV infection
      were tested by 2 rapid immunomigration tests (Witness single [WS], Witness combi
      [WC]) and a plate-based ELISA (Petcheck) for FIV antibody, and by a newly
      designed real-time polymerase chain reaction (PCR) assay for FIV provirus. Four
      hundred and ninety-five blood samples from cats being evaluated for FeLV
      infection were tested by 2 rapid immunomigration tests (WS, WC) and a plate-based
      ELISA (Petcheck) for FeLV antigen, and by a FeLV virus isolation technique.
      Results were then analyzed by using a Bayesian statistical method. RESULTS: For
      FIV tests, median sensitivity estimates were 0.98 for WS, 0.97 for WC, 0.98 for
      ELISA, and 0.92 for PCR. Median specificity estimates were 0.96 for WS, 0.96 for
      WC, 0.93 for ELISA, and 0.99 for PCR. For FeLV tests, median sensitivity
      estimates were 0.97 for WS, 0.97 for WC, 0.98 for ELISA, and 0.91 for virus
      isolation. Median specificity estimates were 0.96 for WS, 0.96 for WC, 0.98 for
      ELISA, and 0.99 for virus isolation. CONCLUSIONS: The use of Bayesian statistical
      methods overcomes a variety of methodologic problems associated with diagnostic
      test evaluations, including the lack of a definitive reference test. The
      sensitivity and the specificity of all 6 evaluated screening tests was high:
      however, specificity estimates were slightly lower than those reported by most
      recent studies.

PMID- 17523088
TI  - A comparison of platelet parameters in EDTA- and citrate-anticoagulated blood in
      dogs.
AB  - BACKGROUND: Platelet aggregates are a common artifact in canine blood. Aggregates
      may affect the accuracy of platelet counts, with important consequences for
      patient care. OBJECTIVES: The purpose of this study was to determine if platelet
      counts in dogs were more accurate if blood was collected into citrate instead of
      EDTA as an anticoagulant. METHODS: Blood was collected from 50 dogs with
      neoplasia admitted to the oncology service at Cornell University. EDTA and
      citrate Vacutainer tubes were filled with blood in random order. Platelet counts
      and parameters (mean platelet volume [MPV], platelet distribution width [PDW],
      mean platelet component concentration [MPC], platelet component distribution
      width [PCDW], and automated platelet clump count [APCC]) were determined using an
      optical-based hematology analyzer (ADVIA 120). Blood smears from each
      anticoagulated sample were scored visually for platelet aggregates. RESULTS: The
      median platelet count was significantly lower (median decrease, 27 x 10(9)/L) in
      citrate-anticoagulated blood compared with EDTA-anticoagulated blood. This was
      attributed to platelet activation and aggregation: significantly more aggregates
      were seen in smears of citrate- than of EDTA-anticoagulated blood. Aggregates
      were typically small and not detected by the analyzer. Also, the MPV and MPC (or
      density) were significantly higher (median increase, 3 fL) and lower (median
      decrease, 33 g/L) in citrate-anticoagulated samples, respectively. CONCLUSIONS:
      Platelets aggregate, likely from activation, when blood from dogs with neoplasia
      is anticoagulated with citrate for hematology testing, resulting in lower
      platelet counts. Citrate also yields inaccurate results for MPV and MPC, likely
      because of inadequate sphering of platelets. Thus, we recommend that citrate not
      be used as an anticoagulant when accurate platelet counts are desired in dogs.

PMID- 17523089
TI  - Clinical evaluation of the CA530-VET hematology analyzer for use in veterinary
      practice.
AB  - BACKGROUND: The CA530-VET is a completely automated impedance cell hematology
      analyzer, which yields a 16-parameter blood count including a 3-part leukocyte
      differential. OBJECTIVES: The aim of this study was to examine the operational
      potential of the CA530-VET and its value for use in veterinary practice. METHODS:
      The analyzer was tested for blood carry-over, precision, and accuracy. Comparison
      methods included the CELL-DYN 3500, microhematocrit centrifugation, manual
      platelet (PLT) counting for feline and equine species, and a 100-cell manual WBC
      differential. Blood samples for comparison of the methods were obtained from 242
      dogs, 166 cats, and 144 horses. RESULTS: The carry-over ratio (K) was 0.28% for
      RBC, 0.59% for PLT, 0.32% for WBC, and 0.18% for hemoglobin (HGB) concentration.
      Coefficients of variation (CVs) for within-batch precision and duplicate
      measurement of blood samples were clearly within the required limits, except for
      duplicate platelet counts in cats (8.7%) and horses (9.5%). The WBC count was in
      excellent agreement for dogs and horses and RBC count was in excellent agreement
      for horses. The accuracy of feline WBC counts was not acceptable, with the
      exception of values at the high end of the range. RBC counts in dogs and cats,
      and HGB concentration and MCV in all 3 species were sufficiently accurate. The
      CA530-VET HCT results were in excellent agreement with microhematocrit results in
      horses but exceeded the maximum allowed inaccuracy for cats and dogs. In all
      species, PLT counts established mechanically and manually were not in adequate
      agreement. Large differences were found between the CA530-VET and the manual
      differential percentage for lymphocytes and "mid-sized cells" (monocytes and
      basophilic granulocytes). CONCLUSIONS: The CA530-VET can be considered useful for
      routine canine, feline, and equine blood cell analyses. It should not be
      considered accurate, however, for PLT counts, feline total WBC counts in the
      subnormal and normal range, and leukocyte differentials, except for granulocytes.

PMID- 17523090
TI  - Evaluation of coagulation markers in the plasma of healthy cats and cats with
      asymptomatic hypertrophic cardiomyopathy.
AB  - BACKGROUND: Thrombosis and arterial thromboembolism are frequent complications of
      feline cardiomyopathy, especially when associated with left atrial enlargement.
      Markers of activated coagulation may be used to evaluate the coagulation status
      of cats with hypertrophic cardiomyopathy (HCM) in relation to left atrial size.
      OBJECTIVES: The objective of this study was to compare plasma concentrations of
      thrombin-antithrombin complex (TAT), D-dimer, and fibrin degradation products
      (FDP) between clinically healthy cats and cats with HCM. Prothrombin time (PT),
      activated partial thromboplastin time (aPTT), and antithrombin activity were also
      compared and the association between left atrial (LA) size and coagulation
      results in cats with HCM was evaluated. METHODS: Blood samples from 19 clinically
      healthy cats and 20 cats with HCM were obtained. All cats with HCM were
      asymptomatic and had no signs of heart failure. LA diameter and LA to proximal
      aortic (Ao) diameter ratio (LA:Ao) were determined by echocardiography. RESULTS:
      Reference intervals for D-dimer and TAT concentrations in plasma of healthy cats
      were established as 0.09-0.32 microg/mL and 2.0-20.0 microg/L, respectively. TAT,
      D-dimer, and FDP concentrations were increased in 5, 3, and 2 cats with HCM,
      respectively. TAT and D-dimer concentrations, and PT and aPTT were not
      significantly different between groups. Antithrombin activity was significantly
      decreased in cats with HCM (P=.03) despite marked range overlap. LA and LA:Ao
      were not correlated with coagulation results. CONCLUSIONS: Laboratory evidence of
      hypercoagulability was found in 45% of cats with HCM. Left atrial size was not
      associated with laboratory evidence of hypercoagulability. Association between
      coagulation markers and risk of thrombosis has yet to be evaluated in cats with
      HCM.

PMID- 17523091
TI  - Beta-2-microglobulin levels in the cerebrospinal fluid of normal dogs and dogs
      with neurological disease.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) analysis is the basis for establishing a
      diagnosis of central nervous system (CNS) inflammation. However, the information
      provided by routine CSF analysis is limited. Determination of CSF beta-2
      microglobulin (beta2m) concentration has been used diagnostically in humans to
      identify inflammatory CNS disease; we hypothesized that it may have similar value
      in dogs. OBJECTIVES: The objective of this study was to measure (beta2m
      concentration in the CSF of clinically healthy dogs and compare the values to
      those observed in dogs with inflammatory CNS disease and intervertebral disc
      disease (IVDD). METHODS: CSF was collected from 10 clinically healthy laboratory
      dogs and 11 dogs each with inflammatory CNS disease and IVDD. Routine CSF
      analysis was performed, and (beta2m concentration was measured by ELISA. CSF
      (beta2m concentration and CSF:serum (beta2m ratio were compared between groups by
      ANOVA. Linear relationships between CSF total nucleated cell count (TNCC), RBC
      count, total protein concentration, and (beta2m concentration were assessed by
      regression analysis. RESULTS: The mean (+/- SD) CSF (beta2m concentration in
      clinically healthy dogs was 0.36 (+/- 0.05 microg/mL (cisternal) and 0.40 (+/-
      0.07 microg/mL (lumbar). Median CSF (beta2m concentration in dogs with IVDD (0.46
      microg/mL) and inflammatory CNS disease (0.85 microg/mL) differed from that of
      controls (0.36 microg/mL; P=.002). The concentration also differed between the 2
      disease groups (P=.01). Five dogs with inflammatory CNS disease had CSF:serum
      (beta2m ratios >1. A correlation was identified between TNCC and (beta2m
      concentration (r=0.69, P=.0003). CONCLUSIONS: CSF (beta2m concentration is higher
      in dogs with IVDD and inflammatory CNS disease, with highest values seen with
      inflammatory disease. This may be attributed in part to the correlation between
      CSF (beta2m concentration and TNCC, but also may reflect intrathecal immune
      activation.

PMID- 17523092
TI  - Performance of 2 microtiter canine Coombs' tests.
AB  - BACKGROUND: The Coombs' test, which detects immunoglobulin or complement on RBC
      surfaces, has long been the standard for laboratory confirmation of immune
      mediated hemolytic anemia (IMHA), a common cause of hemolytic anemia in the dog.
      This test, however, suffers from relatively low sensitivity. Optimization of test
      sensitivity would lead to fewer discrepancies between laboratory results and
      clinical diagnoses, and in some cases institution of appropriate therapy in a
      timely manner. OBJECTIVES: The objectives of this study were to 1) characterize
      the sensitivity and specificity of 2 canine Coombs' tests for the detection of
      IMHA, 2) document the efficacy of using multiple antisera dilutions beyond what
      is directed by manufacturers, and 3) evaluate the necessity of monovalent
      antisera in the test protocol. METHODS: Sixty-five canine whole-blood samples
      submitted for Coombs' testing were evaluated. Patients were classified as IMHA
      positive or negative based on a set of predetermined criteria. IMHA
      classification was compared to Coombs' test results from 2 different Coombs'
      tests adapted to a microtiter-plate format. One Coombs' test (VMRD Coombs' test)
      utilized a single polyvalent antiserum (VMRD, Inc, Pullman, WA, USA), while a
      second Coombs' test (University of Minnesota [U of MN] Coombs' test) used both
      polyvalent and monovalent antisera. RESULTS: Sensitivity and specificity were 61%
      and 100% for the VMRD Coombs' test, and 82% and 95% for the U of MN Coombs' test.
      The use of multiple antisera dilutions resulted in 6 additional Coombs' positive
      test results. All positive Coombs' test results were positive by polyvalent
      antisera. CONCLUSIONS: When used in a microtiter-plate format, the U of MN
      Coombs' test was a more sensitive test for the detection of IMHA in canine
      patients when compared to the VMRD Coombs' test. The use of multiple antisera
      dilutions increased test sensitivity. Sensitivity, however, was not increased by
      the use of monovalent antisera in the Coombs' test protocol.

PMID- 17523093
TI  - Effects of a single injection of methylprednisolone acetate on serum biochemical
      parameters in 11 cats.
AB  - BACKGROUND: Therapeutic use of corticosteroids has been implicated in a variety
      of serum biochemical abnormalities in dogs; however, the effects in cats are less
      well characterized. OBJECTIVE: The objective of this brief communication is to
      report serum biochemical changes in response to methylprednisolone acetate (MPA)
      in adult cats. METHODS: Serum biochemical profiles were performed on 11 cats with
      dermatologic diseases at baseline, 3-6 days, and 16-24 days after a single
      intramuscular dose of 5 mg/kg MPA. RESULTS: Median serum albumin and bicarbonate
      concentrations and amylase activity were increased compared to baseline at both
      post-treatment time points; aspartate aminotransferase activity and magnesium
      concentration were increased at 3-6 days post-treatment only; and alkaline
      phosphatase activity and total calcium concentration were increased at 16-24 days
      post-treatment only. Median serum creatinine concentration was decreased compared
      to baseline at both post-treatment time points. Examination of data from
      individual cats revealed significant variability in serum biochemical changes in
      response to MPA. No adverse clinical reactions to the drug were reported.
      CONCLUSIONS: A single dose of MPA results in significant changes in some serum
      biochemical values in cats, although individual responses will vary.

PMID- 17523094
TI  - Serum biochemistry and hematology values and hemoglobin electrophoresis in
      Persian squirrels (Sciurus anomalus).
AB  - BACKGROUND: Serum biochemical and hematologic parameters are important in the
      management of game species in Iran, such as Persian squirrels. OBJECTIVE: The
      purpose of this study was to establish baseline serum chemistry and hematology
      values in Persian squirrels (Sciurus anomalus) and describe blood cell morphology
      and the electrophoretic pattern of hemoglobin. METHODS: Blood samples were
      collected from 30 Persian squirrels (Sciurus anomalus) maintained in captivity in
      the Tehran Zoo. Blood was placed into EDTA and serum clot tubes and analyzed
      using standard manual hematology and biochemical techniques. Hemoglobin
      electrophoresis was done on cellulose acetate paper strips. RESULTS: Minimum,
      maximum, and median values were obtained for 11 hematologic and 12 serum
      chemistry parameters. Hypersegmented neutrophils were observed frequently. We did
      not find basophils or band neutrophils. Hemoglobin electophoresis resulted in a
      band slightly anodal to that of human hemoglobin A. CONCLUSION: Biochemical and
      hematologic values in Persian squirrels were comparable to those of related
      species, and may be used as a standard profile for healthy Persian squirrels kept
      in captivity.

PMID- 17523095
TI  - Serum markers of lipid peroxidation, antioxidant enzymatic defense, and collagen
      degradation in an experimental (Pond-Nuki) canine model of osteoarthritis.
AB  - BACKGROUND: Chondrocyte lipid peroxidation is strongly suggested to mediate
      collagen degradation and thus, to be involved in the pathogenesis of cartilage
      degradation and osteoarthritis (OA). OBJECTIVES: The objective of this study was
      to evaluate early changes in serum biochemical indicators of oxidative stress
      during the development of OA in a canine model. METHODS: Experimental OA was
      induced in 7 dogs by transection of the anterior cruciate ligament (Pond-Nuki
      model). Venous blood samples were obtained prior to the operation and on
      postoperative days 30, 60, and 105. The activity of serum catalase (an
      antioxidant enzyme), malondialdehyde (MDA) concentration (a marker of lipid
      peroxidation), and serum C2C neoepitope concentration (a marker of collagen type
      II degradation) were measured. RESULTS: A statistically significant increase in
      all parameters as early as the 30th postoperative day was observed, compared with
      preoperative values. Serum catalase activity peaked on day 60, whereas MDA and
      C2C concentrations increased continuously until the end of the experimental
      period. A significant positive correlation was found between MDA and C2C
      concentrations, but not between catalase activity and MDA or C2C concentrations.
      CONCLUSIONS: The results support the hypothesis that oxidative stress is involved
      in the pathogenesis of OA in the dog based on the Pond-Nuki model. The
      correlation between MDA and C2C concentrations suggests a possible association
      between oxidative stress and cartilage degeneration.

PMID- 17523096
TI  - Postmortem diagnosis of idiopathic hyperammonemia in a horse.
AB  - A 6-year-old Quarter Horse stallion was referred to Oklahoma State University
      Veterinary Medical Teaching Hospital for evaluation of abdominal pain that
      developed after breeding activity earlier in the day. The horse developed
      diarrhea and progressively worsening neurologic signs (circling, ataxia, head
      pressing) within 22 hours of presentation and was subsequently euthanized due to
      severe self-destructive behavior. Antemortem biochemical and hematologic
      abnormalities included hypocalcemia but no evidence of hepatic disease.
      Idiopathic hyperammonemia and encephalopathy were suspected; cerebrospinal fluid
      (CSF) and aqueous humor were collected 10 hours postmortem for ammonia analysis
      using a colorimetric assay. Results were compared with those of 6 horses that
      also had been euthanized, for diseases unrelated to encephalopathy. Ammonia also
      was measured in plasma samples obtained antemortem. Ammonia concentrations in
      plasma (958 micromol/L), CSF (1566 micromol/L) and aqueous humor (1018
      micromol/L) samples from the stallion were markedly increased compared to those
      in the 6 unaffected horses (plasma, 9-43 micromol/L; CSF, 370-532 micromol/L;
      aqueous humor, 70-483 micromol/L). Since the acute nature of hyperammonemic
      encephalopathy often does not provide sufficient time for an antemortem
      diagnosis, postmortem analysis of CSF and aqueous humor ammonia concentrations
      may be a useful alternative for documenting hyperammonemia in horses.

PMID- 17523097
TI  - A true "triphasic" pattern: thoracolumbar spinal tumor in a young dog.
AB  - An 8-month-old male Bernese Mountain Dog was referred with a history of hindlimb
      weakness that progressed to paresis on the right side. An intradural mass was
      detected in the spinal canal at the level of the 2nd and 3rd lumbar vertebrae.
      During surgical removal, 2 small fragments of the mass were prepared for
      cytologic examination by the squash technique. Cytologic examination revealed 3
      different cell types: mesenchymal (stromal) cells, epithelial cells, and small
      undifferentiated hyperchromatic cells. On the basis of location and the triphasic
      cytologic pattern, a diagnosis of spinal nephroblastoma (thoracolumbar spinal
      tumor of young dogs) was made; histologic examination of the mass confirmed the
      cytologic diagnosis. To our knowledge, this is the first report of a triphasic
      pattern in a cytologic sample; recognizing this pattern is an important aid in
      reaching a definitive cytologic diagnosis.

PMID- 17523098
TI  - Glanzmann thrombasthenia in an Oldenbourg filly.
AB  - An 18-month-old Oldenbourg filly was presented with a bleeding diathesis.
      Laboratory testing included platelet count, gingival bleeding time, prothrombin
      time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor
      (vWf) antigen, clottable fibrinogen, clot retraction time, PFA-100 closure time,
      platelet aggregometry (on platelet-rich plasma), and thrombelastography (TEG).
      TEG was performed by using kaolin and tissue factor as coagulation activators.
      Expression of the platelet receptor for fibrinogen was assessed by flow cytometry
      by using anti CD41 (alpha(IIb) or glycoprotein IIb)/CD61 (beta(III) or
      glycoprotein IIIa) and anti-CD41 antibodies. Abnormal laboratory findings
      included prolonged oral mucosal bleeding time (>12 hours), prolonged closure time
      with collagen/ADP (>300 seconds), and absence of clot retraction after 60
      minutes. TEG reaction times were similar with kaolin and tissue factor in the
      patient and a control horse. However, maximum amplitudes in the patient were
      decreased with both kaolin (43.7 mm; control, 63.9 mm) and tissue factor (37.7
      mm; control, 57.8 mm). Platelet aggregation responses to ADP and collagen were
      profoundly reduced in the affected horse compared with a control. Flow cytometry
      showed an absence of CD41 and decreased expression of CD41/CD61-reacting antigen
      on the patient's platelets compared with those from a control horse. The
      laboratory findings supported a diagnosis of Glanzmann thrombasthenia, likely
      caused by a mutation in the gene encoding the GPIIb subunit.

PMID- 17523099
TI  - Blood smear from a pregnant cat that died shortly after partial abortion.
AB  - A 1-year-old, 5- to 6-week pregnant cat was presented with a history of aborting
      3 kittens the previous night. During the examination, the cat began to seizure
      and died. At necropsy, formalin-fixed tissues and blood smears prepared from an
      EDTA blood sample collected via cardiac puncture were submitted to a diagnostic
      laboratory. Examination of the blood smears revealed numerous large (15-75
      microm) clumped macrophages containing dark blue intracytoplasmic organisms
      consistent with Cytauxzoon merozoites. Scattered erythrophagocytic macrophages
      were also observed. Within several erythrocytes, 1-2 small, round, ring-like
      piroplasms consistent with Cytauxzoon were observed. Histologic examination
      revealed numerous large, schizont-laden macrophages filling the blood vessels of
      multiple organs. The cytologic and histologic findings were diagnostic for
      Cytaxuzoon felis infection. This case was of particular interest because of the
      unusually large number of organism-laden macrophages in the cardiac blood sample,
      an uncommon finding in peripheral blood. Although the cat was presented for
      complications of abortion, it remains uncertain whether C felis organisms crossed
      the placenta and infected the fetuses or lead to the abortions.

PMID- 17523100
TI  - Spirochetemia caused by Borrelia turicatae infection in 3 dogs in Texas.
AB  - Spirochetemia was diagnosed in 2 Siberian Huskies and a Rottweiler from the
      northwestern region of Texas between June 1999 and October 2001. Clinical
      findings were nonspecific; tick exposure was documented in 2 of the dogs.
      Hematologic abnormalities included anemia (n=2), neutrophilia (n=2, including 1
      with a left shift), lymphopenia (n=3), eosinopenia (n=3), and thrombocytopenia
      (n=2). One anemic dog had a positive Coombs' test. In 1 dog, Western blot
      analysis of serum yielded multiple positive bands with B turicatae lysate,
      indicating the spirochetemia most likely was due to B turicatae infection. In 2
      dogs, spirochetes were cultured from the blood and identified using DNA analysis
      as Borrelia turicatae; 1 of these dogs also was seropositive for Ehrlichia canis
      and B burgdorferi. In 2 cases, spirochetemia was more prominent in blood smears
      prepared immediately after sample collection than in smears prepared from EDTA
      blood. Two dogs recovered with doxycycline treatment; 1 dog declined clinically
      despite treatment and was euthanized. B turicatae is the agent of tick-borne
      (endemic) relapsing fever in humans and is distinct from B burgdorferi, the agent
      of Lyme disease; however, serologic cross-reactivity may occur. B turicatae is
      transmitted by the soft tick, Ornithodoros turicata, and infection should be
      considered in dogs with spirochetemia and possible exposure to the tick vector.

PMID- 17523101
TI  - [The neuroprotective effect of pre and perinatal nutritional factors on
      neurodevelopment].
AB  - INTRODUCTION: The development of the nervous central system is a dynamical
      process determined genetically and modulated by neurochemical, nutritional and
      environmental factors. DEVELOPMENT: It refers to the neuroprotector effect of the
      pre and perinatal nutritional factors, specially proteic-energetic intake, long
      chain polyinsatured fatty acid, vitamins, minerals, choline, maternal metabolic
      disorders and the maternal pseudo-nutritive agent intake. CONCLUSION: For a
      better neurodevelopment, it is necessary that pregnant receives, even before
      conception, a suitable intake of macro and micronutrients.

PMID- 17523102
TI  - [Identification of stem cells in the adult human brain].

PMID- 17523103
TI  - [The genetic origin of neurodevelopmental disorders: the model of neural tube
      closure defects].

PMID- 17523104
TI  - [The effects of prenatal exposure to environmental pollutants and the mother's
      diet on neurodevelopment. The 'Infancy and Environment' Research Network (INMA
      Network) The effects of prenatal exposure to environmental pollutants and the
      mother's diet].

PMID- 17523105
TI  - [Newborn neurometabolic diseases as a cause of neurodevelopmental disorders].
AB  - INTRODUCTION: Foetal distress and hypoxic-ischaemic encephalopathy are two of the
      most frequent causes of neonatal morbidity and mortality. They can be caused by a
      number of factors. Uterine and intrapartum asphyxia are the two most common
      causes; nevertheless, there are also other causing factors that are not usually
      considered, such as inborn errors of metabolism (IEM), for example.
      Manifestations can be very different, not particularly specific and easily
      mistaken for the first two situations. The neonatologist and, later, the
      neuropaediatrician must be familiar with the initial clinical-biochemical
      presenting symptoms, as they can often mimic the clinical picture of hypoxic
      ischaemic encephalopathy or the foetal distress. Once the most common causes have
      been ruled out and working in collaboration with the clinical biochemist and
      neuropaediatrician, they will be able to offer guidance on the complex diagnostic
      and therapeutic approach. In recent years, the combination of the wider
      experience held by departments and modern laboratory techniques has made it
      possible to establish much earlier diagnoses and treatments that are of greater
      benefit to the affected patients. DEVELOPMENT: In this review we analyse the
      clinical presenting symptoms in a consecutive series of 51 newborn infants with
      neurological manifestations and who were finally diagnosed with IEM. CONCLUSIONS:
      The diagnostic approach and prognosis will vary considerably, while genetic
      counselling can be offered and prenatal diagnosis can sometimes be performed.
      Unfortunately, the prognosis of IEM with inborn neurological manifestations is
      still uncertain and the morbidity and mortality rates remain high.

PMID- 17523106
TI  - [The effect of neonatal convulsions and antiepileptic drugs on the developing
      brain: controversial aspects and therapeutic implications].
AB  - INTRODUCTION: Neonatal seizures are the clinical or subclinical manifestations of
      epileptic nature during the first 28 days of life. Their pathophysiological basis
      depends on the anatomic and biochemical characteristics of the developing brain.
      The question whether neonatal seizures cause brain damage, even today, has not a
      clear answer. DEVELOPMENT: Data from clinical cases suggest that neonatal
      seizures may increase the cerebral blood flow and augment the energy requirements
      of the developing brain. Clinical research studies also suggest that neonatal
      seizures, even when they are only electrographic, may cause brain lesion
      independently from their cause. Multiple experimental investigations using mostly
      rat models of isolated or repeated induced seizures, have demonstrated that
      neonatal seizures may alter brain metabolic content, maturation of glutamatergic
      and GABAergic receptors, future cognitive development and epileptogenic risk,
      neuroneogenesis, intranuclear penetration of calcium, and neuronal apoptotic
      activation. On the other hand, some experimental studies suggest that
      phenobarbital, phenytoin and benzodiazepines may have a negative effect on brain
      development. CONCLUSIONS: In my opinion, the ideal short-term goal of treating
      neonatal seizures should be stopping not only the clinical but also the
      subclinical epileptic activity. If prolonged treatment is necessary, one should
      consider to stop it as soon as the clinical and EEG course allows it. There is a
      need for future randomized, controlled trials of sufficient statistical power to
      assess the efficacy and tolerability of classic and new antiepileptic drugs in
      the treatment of neonatal seizures.

PMID- 17523107
TI  - [Early care of neurodevelopmental disorders. Advantages of early intervention in
      neurodevelopmental disorders Early care of neurodevelopmental disorders.
      Advantages of early intervention in neurodevelopmental disorders].
AB  - INTRODUCTION: The model of early assistance implemented in our country is defined
      and developed in the White Paper on Early Intervention (Libro Blanco de Atencion
      Temprana). This model refers to a set of interventions aimed at children with
      neurodevelopmental problems between 0 and 6 years of age. Aims and development.
      The aim of this review is to explain the biological foundations underlying the
      theoretical arguments in favour of intervention and to analyse the different
      techniques that are applied to optimise the development of children with
      different kinds of disabilities. CONCLUSIONS: Although strong theoretical
      arguments have been put forward to defend early intervention, no solid
      conclusions can be drawn as far as its effectiveness is concerned because of the
      diversity of intervention techniques, the lack of homogeneity in treatments and
      the variety of problems that are included under the concept of neurodevelopmental
      disorders.

PMID- 17523108
TI  - [In favour of early detection and moderate interventionism: to what extent is
      early stimulation effective?].
AB  - AIM: To review the bases and outcomes of early stimulation in the light of the
      results reported in the literature. DEVELOPMENT: We survey the papers that report
      results obtained from early stimulation in children at risk and in others with
      known dysfunctions, who were treated using diverse techniques with heterogeneous
      theoretical bases, programmes of intervention and application times and which
      range from the early stages of life (neonatal intensive care units) to the later
      stages of development. The main data taken into account were the meta-analyses.
      No data were found indicating permanent positive effects on the neurodevelopment
      of children to whom stimulation techniques were applied and, when short-term
      effects were reported, they were not detected in the medium or long term.
      CONCLUSIONS: Early stimulation techniques are politically correct, but are not
      effective enough to make their application recommendable as a valid preventive
      procedure. We suggest applying the treatments to children with known impairments
      in order to prevent the appearance of the self-fulfilling prophecy effect.

PMID- 17523109
TI  - [Prognosis of neurodevelopmental disorders from clinically-based criteria:
      usefulness of the observation of general movements].
AB  - INTRODUCTION AND DEVELOPMENT: Some of the most known classical forms for
      neurological examination of neonates and infants are reviewed, and their
      predictive qualities are discussed. Moreover the Prechtl's method of observation
      of general movements in preterm and term neonates and young infants up to four
      months posterm is particularly powerful for prediction of normality or
      abnormality of the future motor control. CONCLUSION: In general, the clinical
      approach is the principal tool in developmental neurology, even if it must be
      complemented by technological examinations, specially neuroimaging.

PMID- 17523110
TI  - [Cognitive repercussion of early-onset epilepsies].
AB  - INTRODUCTION: From time to time the debate over whether early-onset epileptic
      seizures are harmless or have harmful effects on the developing brain reappears.
      DEVELOPMENT: We evaluated the results of clinical studies reporting the long-term
      cognitive development of children who suffer from early-onset epilepsies, that is
      to say, in children with brain immaturity: neonatal epilepsies, West's syndrome,
      Dravet's syndrome, benign myoclonic epilepsy in infancy, myoclonic-astatic
      epilepsy and Lennox-Gastaut syndrome; we also report on the harmful influence of
      certain antiepileptic drugs, such as phenobarbital and valproate, on the immature
      brain. CONCLUSIONS: The negative repercussion of early-onset epilepsies on the
      immature brain is unquestionable, with sometimes very intense impairment of
      cognitive development. As a result, we make the following recommendations: early
      electro-clinical diagnosis, immediate treatment, timely change of medication if
      the seizures persist, avoid phenobarbital and valproate, and try other drugs or
      compounds that have proved to have neuroprotective effects in experimental
      studies.

PMID- 17523111
TI  - [Attention deficit hyperactivity disorder: in favour of the organic origin].
AB  - AIM: To review the neurobiological findings that evidence the organicity of
      attention deficit hyperactivity disorder (ADHD). DEVELOPMENT: The manifest
      inheritability favours the idea of a genetic base for the disorder. Functional
      neuroimaging techniques enable us to observe how the brains of ADHD patients
      function in real time. The most relevant work carried out in the field of
      neuroanatomy shows that the brains of children with ADHD are smaller and the same
      is also true of the cerebellum. On analysing more advanced techniques like
      magnetoencephalography, neurophysiological and functional studies have also
      revealed the existence of differences compared to healthy subjects. CONCLUSIONS:
      Genetic tests have made it possible to focus research towards specific
      neurotransmitter systems, although the results are far from conclusive. Children
      with ADHD present alterations in their brain anatomy and neurophysiology, and
      magnetoencephalography studies have revealed an alteration in very early phases
      of information processing (before 200 ms). They have an early immature response
      in the left inferior parietal lobe, as well as in the posterior-superior temporal
      gyrus, and there is hardly any reaction in the anterior cingulate cortex. This
      implies that, although they perceive the stimulus and even display a stronger
      reaction to it, they do not process it as an interactive signal in the sector of
      the cingulate cortex. These data support the neurobiological bases of ADHD and,
      together with others, will allow for the production of endophenotypical
      classifications based on biological and, in the longer term, genetic evidence.

PMID- 17523112
TI  - [Genetic advances in attention deficit hyperactivity disorder].
AB  - AIM: To update the knowledge currently available on the genetic foundations of
      attention deficit hyperactivity disorder (ADHD). The presentation will focus
      especially on recent data concerning adults. DEVELOPMENT AND CONCLUSIONS: ADHD is
      one of the most prevalent neuropsychiatric disorders among the general childhood
      population. In recent years it has been shown that it often progresses into
      adulthood. The results from studies of families, twins and adopted children
      display a high degree of familial aggregation. Molecular genetics studies have
      brought to light positive associations with different genetic polymorphisms in
      neurotransmitter systems involved in the pathophysiology of ADHD, mainly with the
      dopaminergic, serotoninergic and noradrenergic, and neurotrophins such as the
      brain-derived neurotrophic factor (BDNF). The causation of ADHD is still largely
      unknown but the different studies published to date dealing with the genetic
      foundations of the disorder suggest that genetics play an important role, its
      inheritance is complex and it is modulated by environmental factors. ADHD in
      adults can be a good model for studying the genetic foundations of ADHD.

PMID- 17523114
TI  - [Prognostic factors of functional recovery in very elderly stroke patients. A one
      year follow-up study].
AB  - INTRODUCTION: Although an advanced age is a factor associated to a poorer
      functional prognosis following a stroke, the capacity for recovery can be
      determined by other intercurrent clinical, functional and mental factors. AIM: To
      evaluate the factors that determine the functional prognosis on discharge of very
      elderly patients who were admitted to hospital for their functional recovery
      after suffering a stroke. PATIENTS AND METHODS: We conducted a longitudinal
      observational study of 168 patients over 65 years of age, who were hospitalised
      consecutively over a 15-month period. On admission, data concerning a number of
      clinical, neurological, functional and mental variables were collected. On being
      discharged from hospital their functional situation (Barthel index) and
      institutionalisation were evaluated. RESULTS: The 48 patients aged 85 and above
      presented a lower degree of overall and relative functional recovery on discharge
      from hospital. Nevertheless, 52% had gained more than 20 points on the Barthel
      index on being discharged with respect to their score when they were admitted; on
      discharge 44% had recovered over 50% of the functional loss they had suffered
      following the stroke. On including the other basal variables in a logistic
      regression analysis, a very advanced age was associated in an independent manner
      to a greater risk of being institutionalised, but not to a poorer functional
      prognosis at discharge. Severe functional impairment on admission and post-stroke
      depression were the factors that were independently associated to moderate-severe
      disability on admission; in addition, the more severe the neurological
      consequences were, the lower the level of functional recovery was. CONCLUSIONS:
      The capacity for functional recovery in very elderly stroke patients is mainly
      determined by the degree of functional and neurological repercussion. The
      functional prognosis should be individualised according to these factors,
      regardless of the age.

PMID- 17523115
TI  - [Moebius sequence: clinico-radiological findings].
AB  - INTRODUCTION: Moebius syndrome is an infrequent congenital, non-progressive
      disorder that is defined by facial palsy (usually bilateral) and oculomotor
      compromise. Its clinical spectrum is variable but it affects other cranial nerves
      and is associated with multiple malformations. PATIENTS AND METHODS: We report
      the clinical, neurological and neuroimaging features and the progress of 20
      patients (16 males and 4 females) who satisfied diagnostic criteria for Moebius
      sequence. RESULTS: Ages at the first visit ranged from 9 days to 23 months.
      Births had been normal in 50% of the patients. Facial nerve compromise was
      observed in all cases, 70% being bilateral. Cranial nerves VI (85%), XII (40%),
      VIII (25%) and IX (60%) were also involved. Perinatal respiratory distress was
      seen in 35% of the patients, apnoeas in 25% and retarded development in 60% of
      cases. They also presented other associated malformations such as
      microretrognathia, ogival palate, club foot, hand and foot malformations, and
      four cases presented unilateral agenesis of the pectoralis major. An
      electromyogram study showed absence of spontaneous and voluntary activity and
      muscle evoked potentials on stimulating the facial nerve; magnetic resonance
      imaging of the brain showed hypoplasia of the trunk, agenesis of the cranial
      nerves and abnormalities in the posterior fossa in three of the ten cases in
      which the scan was performed. CONCLUSIONS: The association of multiple
      malformations and dysfunction of the cranial nerves suggests a disruption in the
      process of morphogenesis during the embryonic period, and therefore Moebius
      syndrome is considered to be a malformative sequence.

PMID- 17523116
TI  - [Attention deficit hyperactivity disorder: intellectual profile and the freedom
      from distraction factor].
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) usually presents a
      neuropsychological profile in which the freedom from distraction factor (FDF) is
      affected to a greater extent than the verbal comprehension factor (VCF) and the
      perceptual organisation factor (POF). AIM: To determine the intellectual profile
      of clinical cases with ADHD through a specific analysis of the FDF, in which we
      evaluated the differences compared with the VCF and the POF, between types of
      ADHD and with WISC-R criteria, as well as the variables that affect the
      probability of FDF < VCF and POF. PATIENTS AND METHODS: Our study involved a
      clinical sample of 167 cases of ADHD between 6 and 16 years of age. The cases
      were defined according to DSM-IV criteria and the evaluation was performed using
      WISC-R, the Child Symptom Inventory and the social and occupational activity
      assessment scale. Both descriptive and exploratory statistics were used. Means
      were compared using ANOVA and/or t tests. Alpha was accepted if it was equal to
      or below 0.05 and a logistic regression method was used (alpha model parameters
      below or equal to 0.05). In each factor a 95% confidence interval and odds ratio
      were determined. RESULTS: The criterion FDF < VCF and FOP accounted for 71.3% of
      the cases with ADHD and FDF < (VCF + POF) / 2 represented 81.4% (sensitivity:
      81.4%). The FDF is significantly lower than both the mean that corresponds to
      factorial criteria derived from the WISC-R and the VCF and POF in the cases that
      were analysed. The mean FDF scores were significantly higher in ADHD-H (a type in
      which hyperactive-impulsivity predominates) than in ADHD-C (combined type) and
      ADHD-I (inattentive type). Comorbidity, social or school activity and
      intellectual quotient do not have a significant influence on the probability that
      FDF < VCF and POF. CONCLUSIONS: The FDF is a neuropsychological dimension that is
      useful in evaluating ADHD.

PMID- 17523117
TI  - [Specific impaired language development: a selective or generalised cognition
      problem].
AB  - INTRODUCTION: Specific developmental language disorder (SDLD) is a diagnostic
      entity in which language is expected to be the only cognitive function that is
      affected. Nevertheless, difficulties in other cognitive functions may also
      appear, either because the language disorder is an expression of an underlying
      condition or because the retarded language development gives rise to cognitive
      deficits in general. AIM: To determine whether there are any differences in the
      cognitive performance of children with SDLD and that of children who have
      developed normally. SUBJECTS AND METHODS: The study involved a sample of 51
      children with SDLD, aged between 6 and 16 years, and 49 children in a control
      group, who were paired by chronological age, sex and socioeconomic level. Verbal
      cognitive capacity, attention, memory, visual-constructional and executive
      functioning were all evaluated. RESULTS: Statistically and clinically significant
      differences were found in the verbal-type skills, such as language comprehension
      and verbal cognitive capacity, which showed effect sizes of -1.31 and -1.33,
      respectively. In the other functions that were assessed, the performance of the
      SDLD group was slightly lower than that of the control group, but with no
      clinically significant differences. CONCLUSION: These findings show that the
      group of children with SDLD was well selected, since the only differences between
      the two groups involve linguistic aspects; moreover, this evidence supports the
      idea that language and other cognitive functions are relatively independent and
      that a language disorder would only generate an unspecific general effect in the
      other cognitive functions.

PMID- 17523118
TI  - [The evolution of cerebrovascular accidents in the town of Rivera, Uruguay].
AB  - INTRODUCTION: Improving the health care dispensed to patients who have suffered a
      cerebrovascular accident (CVA) requires a thorough knowledge of its evolution.
      AIMS: To examine the evolution of CVA and its subgroups by looking at the rates
      of mortality, recurrences and extra-neurological complications. We also sought to
      determine the value of different clinical scales and urinary incontinence at the
      beginning of CVA as factors that could potentially predict its severity. A third
      objective was to find out the time elapsed between the onset of CVA and the
      patient's contacting the medical team. PATIENTS AND METHODS: The study, which
      spanned the period between 1st March 2000 and 28th February 2002, was conducted
      in the town of Rivera, which has a population of 62 859 and is located in the
      north of the Eastern Republic of Uruguay. During the first year of the study, 79
      patients with CVA were registered, each of whom was clinically monitored for a
      year. RESULTS: The mortality rate at one month was 24% and at one year rose to
      38%. The validity of certain factors predicting mortality due to CVA was
      confirmed as a lower score on the Glasgow scale, a higher score on the NIH
      impairment scale, and the presence of urinary incontinence, haemorrhagic CVA and
      total anterior circulation syndrome. In 87.3% of cases the patient was attended
      within the first 24 hours. CONCLUSIONS: The findings of this study will make it
      possible to adopt health care strategies to improve the quality of medical
      attention, lower the mortality rate and prevent sequelae in CVA patients.

PMID- 17523119
TI  - [Contiguous gene deletion syndrome in Xp21: the association between glycerol
      kinase deficiency, congenital suprarenal hypoplasia and Duchenne's muscular
      dystrophy].
AB  - INTRODUCTION: Complex glycerol kinase (GK) deficiency is a contiguous deletion of
      genes in Xp21 with loss of the locus for GK, for congenital adrenal hypoplasia
      (AHC) and/or for Duchenne's muscular dystrophy (DMD). We report the case of a 7
      year-old patient with this rare disease. CASE REPORT: Our patient was a full-term
      male, with normal gestation and delivery, and no relevant family history. At the
      age of 11 days he presented a clinical picture of salt loss with lethargy,
      vomiting, metabolic acidosis, hypoglycaemia, hyponatraemia and hyperpotassaemia.
      Fluid therapy and treatment with corticoids was established. The patient's
      condition developed with moderate mental retardation and progressive muscular
      weakness. In the physical examination, the skull and face were seen to be
      'hourglass' shaped. Decompensations associated to infectious processes and
      fasting hypoglycaemia, hydroelectrolytic disorders and ketoacidosis are all
      frequent. Lab findings showed a drop in cortisol levels, elevation of muscle
      enzymes, 'pseudohypertriglyceridaemia' and raised levels of glycerol in plasma
      and urine. Karyotype and neuroimaging tests were normal. A myopathic pattern was
      observed in the electromyogram. The genetic study confirmed the deletion in Xp21
      of the genes responsible for DMD, the GK deficit and AHC. CONCLUSIONS: Early
      identification of this disease makes it possible to foresee the acute metabolic
      decompensations and to establish suitable genetic counselling. CK and
      triglyceride counts should be performed in all male patients that present a
      suprarenal hypoplasia; if levels are high, then it is necessary to confirm the
      raised glycerol values and to carry out a confirmatory genetic study.

PMID- 17523120
TI  - [Glutaric aciduria type I. Clinical, biochemical and molecular findings in six
      patients in Venezuela].
AB  - INTRODUCTION: Glutaric aciduria type I is an autosomal recessive inborn error of
      metabolism that is due to a deficiency of the enzyme glutaryl-CoA dehydrogenase,
      which gives rise to an accumulation of glutaric and 3-hydroxyglutaric acids in
      biological fluids. Clinical features present as a sudden-onset severe
      neurological disorder, characterised by extrapyramidal signs (dystonia
      dyskinesia), hypotonia, irritability, macrocephaly and degeneration of the basal
      ganglia; it may also manifest with unspecific symptoms, such as hypotonia and
      psychomotor retardation. AIMS: To describe the clinical, biochemical,
      neuroimaging and molecular aspects in six Venezuelan patients and to highlight
      the importance of an early diagnosis of glutaric aciduria type I so as to be able
      to establish early treatment and thus prevent the neurological damage produced by
      this disease. CASE REPORTS: Two patients were referred because of macrocephaly,
      hypotonia and psychomotor retardation, and four more following an encephalopathic
      crisis. In all of them, neuroimaging studies showed delays in myelination,
      bilateral frontotemporal hypoplasia and symmetric widening of the Sylvian
      fissures with poor opercularisation. Urinary organic acid analyses showed raised
      levels of glutaric and 3-hydroxyglutaric acids, and a molecular analysis
      confirmed the diagnosis. CONCLUSIONS: Organic acid analysis should be indicated
      in all patients who present macrocephaly, hypotonia, psychomotor retardation or
      an encephalopathic crisis of unknown causation. This study allowed us to
      determine the behaviour of the disease in Venezuela, since no epidemiological
      data exist in the country.

PMID- 17523122
TI  - [Radiological findings in symptomatic and asymptomatic persistent trigeminal
      artery].

PMID- 17523121
TI  - [Treatment of hydrocephalus secondary to intraventricular haemorrhage in preterm
      infants. A review of the literature].
AB  - INTRODUCTION: The current incidence of intraventricular haemorrhage in low-weight
      preterm infants is 20%. The percentage of patients who are going to develop
      hydrocephalus secondary to this haemorrhage varies greatly. In the last 20 years
      different medical and surgical treatments have been put forward to prevent both
      the occurrence of haemorrhage and the development of hydrocephalus. DEVELOPMENT:
      In this study we review the literature on the different treatments used to
      control and treat hydrocephalus. From the medical point of view, treatment with
      pharmacological agents such as azetazolamide or furosemide offers more drawbacks
      than advantages as far as their capacity to prevent hydrocephalus is concerned.
      Treatments involving fibrinolytic agents offer a high risk of triggering new
      haemorrhages but in recent years their use has been taken up again in combination
      with ventricular drains. As regards surgical treatment of hydrocephalus due to
      haemorrhage, despite the risk of infection, it is more advisable to use
      ventricular drains than to introduce subgaleal reservoirs. At the present time,
      the best definitive treatment for hydrocephalus in preterm infants is still the
      ventriculoperitoneal shunt. The most suitable time is when the weight of the
      newborn infant exceeds 1500 g and the cerebrospinal fluid offers a protein count
      above 200 mg/dL. CONCLUSIONS: The long-term neurological development of these
      children depends mainly on the severity of the haemorrhage, but poorer prognoses
      are observed in cases in which complications arise from the control examinations
      of the valve shunt systems.

PMID- 17523124
TI  - [Status epilecticus, dissection of the vertebral artery and ischaemic vascular
      accident in the pons].

PMID- 17523125
TI  - [Locked-in state mimicking cerebral death in a child with Guillain-Barre
      syndrome].

PMID- 17523126
TI  - [Recurring carotidynia that responds to flunarizine].

PMID- 17523128
TI  - CBT for emotional distress of people with cancer: some personal observations.
AB  - The detrimental effect of a helpless coping response on the quality of life of
      cancer patients is well documented. Helplessness is significantly related to
      emotional distress. There is also evidence that this coping response is an
      independent prognostic factor associated with a significantly increased risk of
      disease recurrence and death. These findings highlight the need to develop
      specific strategies to enable patients to overcome helplessness. Recent research
      in patients with advanced cancer indicates that emotional distress appears to be
      caused by low levels of positive effect. Consequently, attention should be paid
      to the much neglected study of positive psychological states such as fighting
      spirit and resilience. In the meantime, some suggestions-based on clinical
      experience-of inducing and fostering positive effect in our patients are
      outlined.

PMID- 17523129
TI  - Contribution of prenatal imaging to the anatomical assessment of fetal
      hydrocolpos.
AB  - Hydrocolpos may be associated with a lower urinary tract obstruction in a
      spectrum of urorectal malformations ranging from persistent urogenital sinus to
      cloacal dysgenesis. As cloacal dysgenesis carries the worst postnatal prognosis,
      detailed prenatal ultrasound should focus on the fetal pelvic anatomy to provide
      the parents with appropriate prenatal counseling. We report three cases of fetal
      hydrocolpos associated with low urinary tract obstructions, including two with a
      normal appearance of the anal canal and rectum on prenatal ultrasound and one
      with a complex cloacal malformation which contributed to the precise prenatal
      assignment of the malformation in each case within the spectrum of urogenital
      sequence malformations.

PMID- 17523130
TI  - More or less CHAOS: case report and literature review suggesting the existence of
      a distinct subtype of congenital high airway obstruction syndrome.
AB  - Congenital obstruction of the upper airway (CHAOS) is a rare, usually lethal
      abnormality. A literature review of 36 prenatally diagnosed cases of CHAOS and
      the analysis of our own case suggest the existence of a distinct subtype of
      CHAOS, raising important implications for diagnosis and management. Serial fetal
      ultrasound examinations at 17-23 weeks' gestation showed hyperechoic and enlarged
      lungs, mediastinal shift, flattened diaphragm, polyhydramnios and apparently
      fluid-filled esophagus, findings interpreted as bilateral cystic adenomatoid
      malformation Type III. Ultrasound findings normalized around 32 weeks. The
      diagnosis of CHAOS was made after birth at term by direct laryngoscopy prompted
      by ventilatory difficulties and failed attempts at intubation. A pinhole opening
      posterior to the cricoid cartilage allowed the passage of an endotracheal tube.
      Based on observations in our case and those of five similar cases in the
      literature, we describe for the first time a subtype of CHAOS that is
      characterized by minor pharyngotracheal or laryngotracheal communications and
      associated with a less severe natural history and even resolution of ultrasound
      findings. In spite of this, a high index of awareness should be maintained
      because resolution of ultrasound findings does not necessarily indicate
      resolution of underlying pathology.

PMID- 17523132
TI  - Inhibition of endogenous MHC class II-restricted antigen presentation by
      tacrolimus (FK506) via FKBP51.
AB  - The effect of tacrolimus (FK506) on down-regulation of IL-2 production by T cells
      is considered to be mainly responsible for its strong suppression of
      immunological events. In this study, we show that FK506 also has an affect on
      antigen presentation by antigen-presenting cells in vitro. FK506 was able to
      inhibit the presentation of endogenous MHC class II-restricted minor
      histocompatibility antigens in primary dendritic cells (DC) in vitro, but
      cyclosporine A (CsA) and rapamycin (RAP) were not. RNA interference (RNAi)
      mediated reduction of endogenous FK506-binding protein (FKBP)51 expression
      resulted in a marked decrease in antigen presentation, suggesting that FKBP51
      plays a role in endogenous MHC class II-restricted antigen presentation. Since
      our model used naturally expressed cytosolic antigens in primary DC, these
      effects might have been due to novel properties of the immunosuppressive drugs
      and may allow us to elucidate a new paradigm for the immunosuppressive mechanism
      of FK506.

PMID- 17523133
TI  - Malondialdehyde modification of myelin oligodendrocyte glycoprotein leads to
      increased immunogenicity and encephalitogenicity.
AB  - Self proteins may become autoantigenic through structural modification. We
      studied malondialdehydation of recombinant rat (rr) myelin oligodendrocyte
      glycoprotein (MOG), an autoantigen in multiple sclerosis. Malondialdehyde (MDA)
      modification changed protein weight and charge, the location of these adducts
      being mapped by Fourier transform ion cyclotron resonance. Molecular modelling
      revealed significant differences in the MDA-rrMOG three-dimensional structure.
      DBA/1 mice immunised with MDA-rrMOG developed greater proliferative responses and
      more severe experimental autoimmune encephalomyelitis than mice immunised with
      unmodified rrMOG. MDA-rrMOG was taken up more effectively by antigen-presenting
      cells (APC), at least partially through scavenger receptors. Exposure to MDA
      rrMOG led to increased expression of IL-23, IL-12 and IL-12R, indicating a role
      not only for increased antigen uptake but also for activation of APC. We thus
      provide biochemical, structural, immunological and clinical data that suggest
      that the post-translationally modified form of this myelin autoantigen is a more
      relevant form of the molecule.

PMID- 17523134
TI  - Expression and function of the IL-2 receptor in activated human plasmacytoid
      dendritic cells.
AB  - Human and mouse plasmacytoid dendritic cells (PDC) express IL-2 mRNA specifically
      upon TLR stimulation, but not under CD40L stimulation. Even though the expression
      of the IL-2R by PDC has been described, the functional implications of this
      expression remain unknown. Here, we investigated the expression and function of
      the IL-2R in activated human PDC. The IL-2Ralpha chain, CD25, is expressed in
      both CpG- and CD40L-activated PDC. CD25 expression is a relatively rapid event,
      as the receptor was detected 6 h after the initial activation signal. Exogenous
      IL-2 added to CD40L-activated PDC increased the expression of CD25, enhanced the
      secretion of pro-inflammatory cytokines and promotes PDC survival. CpG-activated
      PDC cultured in the presence of IL-2R-blocking monoclonal antibodies showed a
      reduced expression of pro-inflammatory cytokines, especially TNF-alpha. This
      reduction was dose and time dependent, suggesting a regulatory role of IL-2 in
      TNF secretion that might occur at the post-transcriptional level. These results
      indicate that the expression of the IL-2R is relevant to human PDC activation,
      and that IL-2 may be an important auto- and/or paracrine factor modulating the
      activation and survival of PDC. Finally, CD25 expression may be considered as a
      useful early activation marker for human PDC.

PMID- 17523136
TI  - Silver-catalyzed asymmetric allylation: allyltrimethoxysilane as a remarkable
      reagent.
AB  - Recently, there have been some reports on the use of allyltrimethoxysilane for
      enantioselective allylation with various metal fluorides or a combination of
      chiral complex and fluoride anion. These reactions can be applied not only to
      aldehydes but also to ketones and imines. In this Focus Review we discuss the
      development of asymmetric allylation with allyltrimethoxysilane catalyzed by
      chiral silver complexes.

PMID- 17523137
TI  - Characterization of transferrin glycoforms in human serum by CE-UV and CE-ESI-MS.
AB  - Human transferrin (Tf) is a model glycoprotein for congenital disorders of
      glycosylation (CDG) diagnosis. In the last few years, new CE-UV methods for
      intact Tf glycoforms analysis have been developed using nonvolatile BGEs and
      organic modifiers. However, the use of these BGEs does not allow the coupling of
      these procedures with electrospray MS (ESI-MS). In this study, a new CE-UV
      separation method of Tf glycoforms is developed, using a double-layer stable
      coating and a volatile BGE based on ammonium acetate. The separation method is
      optimized using standard Tf and their potential is demonstrated applying the
      method to the analysis of sera Tf from healthy individuals and CDG patients. The
      CE-UV separation method has been coupled to ESI-MS detection. Main parameters
      such as sheath liquid composition are optimized in order to obtain a good
      sensitivity. The CE-ESI-MS method has also been used in serum samples obtaining
      the separation of the different proteins present in serum and partial separation
      of Tf glycoforms. Different mass spectra and deconvoluted molecular masses were
      obtained for each sialoform, allowing unequivocal glycoform identification.

PMID- 17523138
TI  - pI-based phosphopeptide enrichment combined with nanoESI-MS.
AB  - IEF is introduced as a new principle for enrichment and separation of
      phosphopeptides as obtained after digestion of phosphoproteins by trypsin.
      Tryptic peptides and phosphopeptides exhibit pI values, which overlap in the
      range of about 4-6. However, after methyl esterification of all carboxyl
      functions, the pI values of tryptic peptides and phosphopeptides regroup in
      discrete clusters. In addition, mono- and diphosphorylated peptides show
      different but very homogeneous pI values, with variations when internal Arg, Lys,
      or His residues are present. Experimentally, this new concept was applied for
      separation of model peptides on IPG strips pH 3-10 as used in the first dimension
      of 2-DE. After IEF of methyl-esterified peptides, the IPG strip was cut into
      pieces followed by peptide extraction, desalting and MS analysis by nanoESI-MS.
      Phosphopeptides were found to focus in good agreement with their calculated pI
      values. This analytical strategy showed a resolution of about 0.2 pI units, and
      thus turned out to be capable of detecting minor differences in pI values, such
      as those occurring between pSer, pThr and pTyr residues. Using IPG strips with a
      pI range of 3-10, methyl esterified nonphosphorylated tryptic peptides are
      concentrated in the basic part of the IPG strip or even leave the strip. Thus,
      efficient enrichment of phosphopeptides and their subfractionation according to
      pI is obtained in one step. Minor hydrolytic side reactions including deamidation
      of Asn and partial hydrolysis of methyl esters are observed. The results show
      that IEF opens attractive avenues for the further advancement of analytical
      phosphoproteomics.

PMID- 17523139
TI  - Applicability of different fluorescent dyes for isoform quantification on linear
      IPG gels.
AB  - For biotechnological research, development, and production various analytical
      methods are required to determine the quality of the target product. In this
      context, the determination of isoforms is state-of-the-art; however, the majority
      of applied techniques are more qualitative than quantitative. To address this
      fact, we evaluated different post- and pre-electrophoretic staining dyes for
      their applicability on linear IPG gels using recombinant human erythropoietin as
      a model protein. Each evaluated dyes was able to detect all isoforms
      reproducibly, but CyDyes were found to be the most promising. Using CyDyes, up to
      three samples can be focused on the same lane under identical electrophoretic
      conditions, thus, a fast, reproducible, sensitive and quantitative isoform
      determination can be performed. To illustrate the practical relevance,
      quantitative CyDye technique was used for the characterization of our model
      protein, recombinant human Epo-Fc. This method makes it possible to determine the
      isoform pattern of nonpurified supernatants as well as purified proteins. We
      conclude that quantitative pre-electrophoretic staining IEF using CyDyes is a
      fast, simple, accurate method to determine isoforms, which can be used in
      research, development, and manufacturing for product quality analysis, e.g.,
      clone screening, process optimization, and purification monitoring.

PMID- 17523140
TI  - Nuclear protein profiling of Jurkat cells during heat stress-induced apoptosis by
      2-DE and MS/MS.
AB  - Heat stress causes severe constraints on numerous physiological functions of
      cells, such as the repression of splicing of mRNA precursors. In this study, we
      performed proteomic profiling of a nuclear fraction of Jurkat cells during heat
      stress using 2-DE and LC-MS/MS. We found 10 protein spots whose expression had
      changed after heat stress at 43 degrees C for 30 min. Seven of those protein
      spots, periodic tryptophan protein 1 homolog (PWP1), importin beta-1 subunit,
      sumoylated protein, splicing factor 3a subunit 3 (SF3a3), TAR DNA-binding protein
      43, U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit (U2AF35)
      and small ubiquitin-related modifier-1 (SUMO-1) were downregulated, while three
      other protein spots, Protein SET, 40S ribosomal protein SA and 60S acidic
      ribosomal protein P0 were upregulated by the heat stress. We focused on the
      downregulation of two splicing factors, which might participate in the repression
      of pre-mRNA processing by heat stress, leading to cell apoptosis.

PMID- 17523141
TI  - Rapid isoelectric trapping in a micropreparative-scale multicompartment
      electrolyzer.
AB  - A multicompartmental electrolyzer called membrane-separated wells for isoelectric
      focusing and trapping (MSWIFT) has been developed and tested for micropreparative
      scale isoelectric trapping separations. In the MSWIFT, the length of the heat
      conduction path from the center of the compartments to the wall is less than 1
      mm. The compartments are made from 99.8% nonporous alumina that has a high heat
      conductivity and a high specific heat capacity, leading to adequate Joule heat
      dissipation even at power loads as high as 5 W. The length of any compartment
      parallel to the electric field (the intermembrane distance) can be selected to be
      multiples of 1.5 mm, leading to compartment volumes that are multiples of about
      60 muL. A maximum of 20 (1.5 mm long) separation compartments can be readily
      assembled in the current version of MSWIFT. The MSWIFT has been used to desalt
      samples, isolate small ampholytic components (amino acids, peptides, and dyes),
      prefractionate complex protein mixtures and enrich minor components; these
      separations were achieved in 20-60 min.

PMID- 17523142
TI  - Scanning copy number and gene expression on the 18q21-qter chromosomal region by
      the systematic multiplex PCR and reverse transcription-PCR methods.
AB  - We examined differences in copy number and expression of 127 genes located on the
      18q21-qter chromosomal region of the breast and prostate cancer cell lines, using
      the systematic multiplex PCR and reverse transcription-PCR (SM PCR and SM RT-PCR)
      methods that we developed. Semi-quantitative data were obtained that were
      comparable in quality, but not in quantity, to data from DNA microarray
      hybridization analysis. In the chromosomal region where losses are frequent in
      breast, prostate, and other cancers, we detected a homozygous deletion of the
      SMAD4 gene in the MDA-MB-468 breast cancer cell line. We also observed partial or
      entire loss of expression in genes such as CCBE1, CCDC11, CD226, NP_115536.1,
      NP_689683.2, RNF152, SERPINB8, and TCF4 in certain breast and/or prostate cancer
      cell lines. An increase in gene expression was rare, but found with the
      transcription factor ONECUT2 gene in all of the cancer cell lines examined. Real
      time qRT-PCR experiments confirmed these SM RT-PCR results. Further analysis of
      clinical specimens of breast cancer by real-time qRT-PCR demonstrated that the
      gene expression of CCBE1, TCF4, NP_115536.1, and NP_689683.2 was downregulated in
      the majority of clinical cases of breast cancer.

PMID- 17523143
TI  - Pest management programmes in vineyards using male mating disruption.
AB  - Israeli vine growers have been reluctant to adopt the mating disruption technique
      for control of the European vine moth, Lobesia botrana Den. & Schiff. Since the
      chemically controlled honeydew moth, Cryptoblabes gnidiella Mill., coexists with
      the European vine moth, growers have maintained that the use of mating disruption
      would fail to bring about a significant reduction in pesticide use. In this
      study, the efficacy of mating disruption techniques against C. gnidiella was
      tested, as well as the effect of these methods on pesticide use and damage to
      clusters when the method was employed against both of the pests in wine grapes.
      Comparisons were made between plots treated with (1) L. botrana mating disruption
      pheromone, (2) L. botrana and C. gnidiella mating disruption pheromones and (3)
      control plots. A significant difference in the number of clusters infested with
      the developmental stages of the moths was seen between pheromone-treated plots
      and controls, while no such difference was observed between plots treated with
      one versus two pheromones. A similar pattern was observed in the number of
      insecticide applications; the greatest number of applications was used in control
      plots, followed by plots treated with L. botrana mating disruption pheromone and
      by plots treated with pheromones against both pests, in which no pesticides were
      applied.

PMID- 17523144
TI  - Toxicity of insecticides to the sweetpotato whitefly (Hemiptera: Aleyrodidae) and
      its natural enemies.
AB  - Efficient chemical control is achieved when insecticides are active against
      insect pests and safe to natural enemies. In this study, the toxicity of 17
      insecticides to the sweetpotato whitefly, Bemisia tabaci (Gennadius), and the
      selectivity of seven insecticides to natural enemies of this insect pest were
      evaluated. To determine the insecticide toxicity, B. tabaci adults were exposed
      to abamectin, acephate, acetamiprid, cartap, imidacloprid, malathion,
      methamidophos, bifenthrin, cypermethrin, deltamethrin, esfenvalerate,
      fenitrothion, fenpropathrin, fenthion, phenthoate, permethrin and trichlorphon at
      50 and 100% of the field rate (FR), and to water (untreated control). To
      determine the insecticide selectivity, adults of Encarsia sp., Acanthinus sp.,
      Discodon sp. and Lasiochilus sp. were exposed to abamectin, acephate,
      acetamiprid, cartap, imidacloprid, malathion and methamidophos at 50 and 100% FR,
      and to water. Groups of each insect species were exposed to kale leaves
      preimmersed in each treatment under laboratory conditions. Mortality of exposed
      individuals was recorded 24 h after treatment. Cartap and imidacloprid at 50 and
      100% FR and abamectin and acetamiprid at 100% FR showed insecticidal activity to
      B. tabaci adults. Abamectin at 50 and 100% FR was the least insecticidal compound
      to the natural enemies Acanthinus sp., Discodon sp. and Lasiochilus sp. The
      present results suggest that abamectin at 100% FR may decrease B. tabaci field
      populations but can still be harmless to predators. Implications of these results
      within an integrated pest management context are discussed.

PMID- 17523145
TI  - Stereoselective monofluoromethylation of primary and secondary alcohols by using
      a fluorocarbon nucleophile in a Mitsunobu reaction.

PMID- 17523146
TI  - Mass-selective vibrational spectroscopy of vanadium oxide cluster ions.
AB  - A corner stone in the study of the size-dependent properties of cluster ions in
      the gas phase is their structural characterization. Over the last 10 years,
      significant progress has been in this research field because of significant
      advances in the gas phase vibrational spectroscopy of mass-selected ions. Using a
      combination of modern experimental and quantum chemical approaches, it is now in
      most cases possible to uniquely identify the geometric structure of cluster ions,
      based on the comparison of the experimental and simulated infrared spectra. In
      this article, we highlight the progress made in this research area by reviewing
      recent infrared photodissociation (IR-PD) experiments on small and medium sized
      (up to 30 atoms) vanadium oxide ions.

PMID- 17523147
TI  - Impairment of liver regeneration correlates with activated hepatic NKT cells in
      HBV transgenic mice.
AB  - A fraction of HBV carriers have a risk to develop liver cancer. Because liver
      possesses a strong regeneration capability, surgical resection of cancerous liver
      or transplantation with healthy liver is an alternate choice for HBV-caused
      hepatocarcinoma therapy. How HBV infection affects the regeneration of
      hepatectomized or transplanted liver remains elusive. We report that partial
      hepatectomy (PHx)-induced liver regeneration was reduced in HBV transgenic (HBV
      tg) mice, a model of human HBV infection. PHx markedly triggered natural killer T
      (NKT) cell accumulation in the hepatectomized livers of HBV-tg mice,
      simultaneously with enhanced interferon gamma (IFN-gamma) production and CD69
      expression on hepatic NKT cells at the early stage of liver regeneration. The
      impairment of liver regeneration in HBV-tg mice was largely ameliorated by NKT
      cell depletion, but not by natural killer (NK) cell depletion. Blockage of CD1d
      NKT cell interaction considerably alleviated NKT cell activation and their
      inhibitory effect on regenerating hepatocytes. Neutralization of IFN-gamma
      enhanced bromodeoxyuridine incorporation in HBV-tg mice after PHx, and IFN-gamma
      mainly induced hepatocyte cell cycle arrest. Adoptive transfer of NKT cells from
      regenerating HBV-tg liver, but not from normal mice, could inhibit liver
      regeneration in recipient mice. CONCLUSION: Activated NKT cells negatively
      regulate liver regeneration of HBV-tg mice in the PHx model.

PMID- 17523148
TI  - Endotoxemia produces coma and brain swelling in bile duct ligated rats.
AB  - This study explores the hypothesis that the inflammatory response induced by
      administration of lipopolysaccharide (LPS) exacerbates brain edema in cirrhotic
      rats; and if so whether this is associated with altered brain metabolism of
      ammonia or anatomical disturbance of the blood-brain barrier. Adult Sprague
      Dawley rats 4 weeks after bile duct ligation (BDL)/Sham-operation, or naive rats
      fed a hyperammonemic diet (HD), were injected with LPS (0.5 mg/kg,
      intraperitoneally) or saline, and killed 3 hours later. LPS administration
      increased brain water in HD, BDL, and sham-operated groups significantly (P <
      0.05), but this was associated with progression to pre-coma stages only in BDL
      rats. LPS induced cytotoxic brain swelling and maintained anatomical integrity of
      the blood-brain barrier. Plasma/brain ammonia levels were higher in HD and BDL
      rats than in sham-operated controls and did not change with LPS administration.
      Brain glutamine/myoinositol ratio was increased in the HD group but reduced in
      the BDL animals. There was a background pro-inflammatory cytokine response in the
      brains of cirrhotic rats, and plasma/brain tumor necrosis factor alpha (TNF
      alpha) and IL-6 significantly increased in LPS-treated animals. Plasma
      nitrite/nitrate levels increased significantly in LPS groups compared with non
      LPS controls; however, frontal cortex nitrotyrosine levels only increased in the
      BDL + LPS rats (P < 0.005 versus BDL controls). CONCLUSION: Injection of LPS into
      cirrhotic rats induces pre-coma and exacerbates cytotoxic edema because of the
      synergistic effect of hyperammonemia and the induced inflammatory response.
      Although the exact mechanism of how hyperammonemia and LPS facilitate cytotoxic
      edema and pre-coma in cirrhosis is not clear, our data support an important role
      for the nitrosation of brain proteins.

PMID- 17523149
TI  - Characterization of voltage-and Ca2+-activated K+ channels in rat dorsal root
      ganglion neurons.
AB  - Auxiliary beta-subunits associated with pore-forming Slo1 alpha-subunits play an
      essential role in regulating functional properties of large-conductance, voltage-
      and Ca(2+)-activated K(+) channels commonly termed BK channels. Even though both
      noninactivating and inactivating BK channels are thought to be regulated by beta
      subunits (beta1, beta2, beta3, or beta4), the molecular determinants underlying
      inactivating BK channels in native cells have not been extensively demonstrated.
      In this study, rbeta2 (but not rbeta3-subunit) was identified as a molecular
      component in rat lumbar L4-6 dorsal root ganglia (DRG) by RT-PCR responsible for
      inactivating large-conductance Ca(2+)-dependent K(+) currents (BK(i) currents) in
      small sensory neurons. The properties of native BK(i) currents obtained from both
      whole-cell and inside-out patches are very similar to inactivating BK channels
      produced by co-expressing mSlo1 alpha- and hbeta2-subunits in Xenopus oocytes.
      Intracellular application of 0.5 mg/ml trypsin removes inactivation of BK(i)
      channels, and the specific blockers of BK channels, charybdotoxin (ChTX) and
      iberiotoxin (IbTX), inhibit these BK(i) currents. Single BK(i) channel currents
      derived from inside-out patches revealed that one BK(i) channel contained three
      rbeta2-subunits (on average), with a single-channel conductance about 217 pS
      under 160 K(+) symmetrical recording conditions. Blockade of BK(i) channels by
      100 nM IbTX augmented firing frequency, broadened action potential waveform and
      reduced after-hyperpolarization. We propose that the BK(i) channels in small
      diameter DRG sensory neurons might play an important role in regulating
      nociceptive input to the central nervous system (CNS).

PMID- 17523150
TI  - Body fat distribution and metabolic variables in patients with neonatal progeroid
      syndrome.
AB  - Neonatal progeroid syndrome (NPS), also known as Wiedemann-Rautenstrauch
      Syndrome, is a rare autosomal recessive disorder characterized by accelerated
      aging and lipodystrophy from birth. Affected children have extreme intrauterine
      growth retardation, poor postnatal weight gain, and characteristic facial
      dysmorphic features such as a triangular shape, pinched nose, pseudohydrocephalus
      with wide fontanelles and prominent subcutaneous (sc) veins. Generalized loss of
      sc fat has been reported as a cardinal feature; however, the pattern of fat loss
      and its association with insulin resistance and its metabolic complications have
      not been systematically studied. The aim of the current study was to examine body
      fat distribution and body composition in two girls with NPS using anthropometric
      measures, whole-body magnetic resonance imaging (MRI) and dual energy X-ray
      absorptiometry (DEXA), and to assess metabolic complications such as
      hyperinsulinemia and dyslipidemia. Both the girls (aged 17 years and 10 years,
      respectively) had generalized paucity of sc fat on physical examination. However,
      measurements of skin-fold thickness revealed that sc fat was decreased over the
      extremities, but preserved over the chest and abdomen. MRI studies confirmed the
      presence of normal amounts of sc truncal fat, and marked loss of fat from the
      face and distal extremities. Striking fat loss was also noted in the
      paravertebral and lateral gluteal regions. Interestingly, body composition
      analysis with DEXA scan revealed a marked reduction in both the fat and lean
      tissue mass. Fasting glucose, lipids and insulin levels were not elevated. We
      conclude that patients with NPS do not have generalized lipodystrophy as
      previously reported, but fat loss is confined to the face, distal extremities,
      and possibly the paravertebral and lateral gluteal regions. Metabolic
      abnormalities related to insulin resistance are also uncommon in this condition.

PMID- 17523151
TI  - Upper gastrointestinal malformations in Coffin-Siris syndrome.

PMID- 17523152
TI  - Sonohysterography in the preoperative grading of submucous myomas: considerations
      on three-dimensional methodology.

PMID- 17523153
TI  - Two- and three-dimensional transvaginal Doppler ultrasound analysis of urethral
      clear cell carcinoma.

PMID- 17523154
TI  - FLIPDock: docking flexible ligands into flexible receptors.
AB  - Conformational changes of biological macromolecules when binding with ligands
      have long been observed and remain a challenge for automated docking methods.
      Here we present a novel protein-ligand docking software called FLIPDock (Flexible
      LIgand-Protein Docking) allowing the automated docking of flexible ligand
      molecules into active sites of flexible receptor molecules. In FLIPDock,
      conformational spaces of molecules are encoded using a data structure that we
      have developed recently called the Flexibility Tree (FT). While the FT can
      represent fully flexible ligands, it was initially designed as a hierarchical and
      multiresolution data structure for the selective encoding of conformational
      subspaces of large biological macromolecules. These conformational subspaces can
      be built to span a range of conformations important for the biological activity
      of a protein. A variety of motions can be combined, ranging from domains moving
      as rigid bodies or backbone atoms undergoing normal mode-based deformations, to
      side chains assuming rotameric conformations. In addition, these conformational
      subspaces are parameterized by a small number of variables which can be searched
      during the docking process, thus effectively modeling the conformational changes
      in a flexible receptor. FLIPDock searches the variables using genetic algorithm
      based search techniques and evaluates putative docking complexes with a scoring
      function based on the AutoDock3.05 force-field. In this paper, we describe the
      concepts behind FLIPDock and the overall architecture of the program. We
      demonstrate FLIPDock's ability to solve docking problems in which the assumption
      of a rigid receptor previously prevented the successful docking of known ligands.
      In particular, we repeat an earlier cross docking experiment and demonstrate an
      increased success rate of 93.5%, compared to original 72% success rate achieved
      by AutoDock over the 400 cross-docking calculations. We also demonstrate
      FLIPDock's ability to handle conformational changes involving backbone motion by
      docking balanol to an adenosine-binding pocket of protein kinase A.

PMID- 17523155
TI  - Bilateral avulsion of the puborectal muscle: magnetic resonance imaging-based
      three-dimensional reconstruction and comparison with a model of a healthy
      nulliparous woman.
AB  - OBJECTIVES: Obstetric trauma to the puborectal muscle seems to be an important
      cause of pelvic floor dysfunction in women. Due to the complicated three
      dimensional (3D) arrangement of the pelvic structures, two-dimensional images are
      not sufficient to demonstrate its relationships in a complex fashion. Thus, we
      aimed to create a 3D computer model to visualize the normal female pelvic floor
      anatomy and to compare this with the anatomy after bilateral avulsion of the
      puborectal muscle following delivery. METHODS: We created two 3D computer models
      of the female pelvic floor, one of a healthy nulliparous woman and the other of a
      woman with bilateral puborectal muscle avulsion after vaginal delivery. The data
      for the models were obtained from magnetic resonance imaging examinations and the
      following structures were depicted: pelvic bones, puborectal muscle, internal
      obturator muscle, urethra, urinary bladder, vagina and rectum. The models were
      compared. RESULTS: The models allowed us to demonstrate in three dimensions
      changes in the puborectal muscle after avulsion. Its relations to the bone,
      internal obturator muscle, perineal membrane and the deep part of the external
      anal sphincter were modeled and differences from the normal non-injured anatomy
      were demonstrated. Avulsion altered the support to the whole endopelvic fascia
      and destabilized both the anterior and the posterior vaginal walls. CONCLUSIONS:
      The use of 3D technology including modeling allows for the acquisition of new
      knowledge and aids in the understanding of both normal and pathological pelvic
      anatomy.

PMID- 17523156
TI  - Persistent and redundant eustachian valve simulating atrial tumor: prenatal
      diagnosis.
AB  - The eustachian valve, or valve of the inferior vena cava, is an embryogenic
      derivative of the right valve of the sinus venosus. Although it generally
      disappears during fetal life, its persistence may simulate symptoms of cardiac
      disease, particularly those associated with atrial tumors. We describe a case of
      prenatal diagnosis of a persistent, large and prominent eustachian valve with
      redundant tissue attached to the junction of the inferior vena cava and the right
      atrium. The neonate was asymptomatic and was healthy at 7 months of age at the
      time of writing. This is the first time that this finding has been diagnosed
      prenatally.

PMID- 17523157
TI  - A thin and regular endometrium on ultrasound is very unlikely in patients with
      endometrial malignancy.
AB  - OBJECTIVE: To evaluate the clinical and sonographic features in patients with
      endometrial malignancy in whom endometrial thickness on ultrasound examination
      had been recorded in our database to be < 5 mm. METHODS: This was a retrospective
      observational study on 187 consecutive patients diagnosed with endometrial
      malignancy in whom an ultrasound evaluation of the endometrium had been performed
      in our institution. The characteristics of those patients presenting with an
      endometrial thickness < 5 mm were analyzed. RESULTS: The median endometrial
      thickness was 15 mm: 12 mm for the women who underwent endometrial sampling
      before ultrasound examination vs. 17 mm in those who did not (P = 0.0086). In 13
      women (6.9%), the endometrial thickness recorded in our database was < 5 mm. In
      12 of these the measurement was compromised in some way: nine of these patients
      had undergone endometrial sampling (Pipelle biopsy in one and dilatation and
      curettage in eight patients) before the ultrasound examination, in two cases,
      focal malignant lesions were not included in the recorded endometrial thickness
      and in one, the endometrial thickness was visualized poorly due to myometrial
      distortion. In only one case was was the endometrium correctly measured to be < 5
      mm; this woman had diffuse uterine and endometrial metastases of a breast cancer.
      CONCLUSIONS: A thin and regular endometrial line is very reliable for the
      exclusion of endometrial carcinoma. The suspicion of focal lesions as well as
      incomplete visualization of the endometrium on sonography should be considered
      abnormal. Recently performed endometrial sampling makes measurement of the
      endometrial thickness unreliable.

PMID- 17523158
TI  - Cognitive function in young adults following intrauterine growth restriction with
      abnormal fetal aortic blood flow.
AB  - OBJECTIVE: Intrauterine growth restriction (IUGR) is a recognized risk factor for
      neurological deficits later in life. Abnormal fetal blood flow in the presence of
      IUGR helps to distinguish fetuses with true growth impairment from those that are
      small but normally grown. This study aimed to evaluate the influence of IUGR with
      abnormal fetal blood flow on cognitive function and psychological development in
      young adults. METHODS: Cognitive capacity (Wechsler adult intelligence scale-III
      (WAIS-III)) and psychological development (symptom check-list and Wender Utah
      rating scale) were evaluated at 18 years of age in 19 subjects who had had IUGR
      (abnormal fetal blood flow in the descending aorta and birth weight small-for
      gestational age) and in 23 control subjects who had had normal fetal aortic blood
      flow and birth weight appropriate-for-gestational age (AGA). School grades at 16
      years of age were also recorded. RESULTS: The IUGR subjects had significantly
      lower results at 18 years of age in the combined subtests of the WAIS-III
      measuring executive cognitive functions (P = 0.03) and lower school grades at 16
      years of age (P = 0.03) compared with the AGA group. IUGR subjects did not
      exhibit significantly more psychological distress symptoms. CONCLUSION: IUGR with
      abnormal fetal blood flow is associated with impaired executive cognitive
      function in young adults.

PMID- 17523159
TI  - From the fetus at risk to intelligence, educational attainment and psychological
      distress in the young adult.

PMID- 17523160
TI  - Standardization of on-screen fetal heart orientation prior to storage of spatio
      temporal image correlation (STIC) volume datasets.

PMID- 17523161
TI  - Population-based study of antenatal detection of congenital heart disease by
      ultrasound examination.
AB  - OBJECTIVES: Ultrasound-based screening is widely employed for the detection of
      congenital malformations in utero including congenital heart disease (CHD), but
      there is widespread variability in the efficacy of screening programs. We aimed
      to evaluate current antenatal detection rates of selected congenital heart
      defects in Victoria. METHODS: Data were collected from the Victorian Perinatal
      Data Collection Unit and Birth Defects Registry. There were 631 209 births in
      Victoria (1993-2002), of which 4897 cases had CHD. Cases included live births,
      stillbirths and termination of pregnancies because of CHD. We reviewed all cases
      from 1999 to 2002 with atrioventricular septal defect, simple coarctation of the
      aorta, double-inlet or -outlet ventricle, hypoplastic left heart syndrome, simple
      transposition of the great arteries (TGA), tetralogy of Fallot and truncus
      arteriosus. Outcome measures were antenatal diagnosis, pregnancy outcome and
      associated malformations. RESULTS: The overall birth prevalence of CHD from 1993
      to 2002 in Victoria was 7.8/1000. The antenatal detection rate for the seven
      selected defects from 1999 to 2002 was 52.8%. All but 4.8% of the cases had an
      ultrasound examination at > 13 weeks' gestation. Antenatal detection was highest
      for hypoplastic left heart syndrome (84.6%) and lowest for simple TGA (17.0%).
      CONCLUSIONS: This study shows wide variation in the antenatal detection rate of
      CHD in Victoria. The low antenatal detection rate of TGA, a defect that should be
      detected easily, demonstrates suboptimal routine obstetric anomaly scanning.

PMID- 17523162
TI  - Bile salt-dependent efflux of cellular phospholipids mediated by ATP binding
      cassette protein B4.
AB  - Human ABCB4 (multidrug resistance [MDR]3 P-glycoprotein) is expressed in the
      canalicular membrane of the hepatocyte. ABCB4 has been shown to be required for
      phosphatidylcholine (PC) secretion into the bile and to translocate PC across the
      plasma membrane. To further investigate the function of ABCB4, we established a
      cell line stably expressing ABCB4 (human embryonic kidney [HEK]/ABCB4). The
      efflux of phospholipids from HEK/ABCB4 cells was remarkably increased by the
      addition of taurocholate. In addition, the cholesterol efflux from HEK/ABCB4
      cells was also enhanced in the presence of taurocholate. Light scattering
      measurements suggested that the taurocholate monomer plays an important role in
      ABCB4-mediated lipid secretion. On the other hand, the efflux of phospholipids
      and cholesterol was not mediated by ABCB1 (MDR1) even in the presence of
      taurocholate. Taurocholate promoted the efflux of phospholipids and cholesterol
      from HEK/ABCB4 cells more efficiently than glycocholate and cholate. ABCB4-K435M
      and ABCB4-K1075M, Walker A lysine mutants, did not mediate the phospholipid and
      cholesterol efflux in the presence of taurocholate, suggesting that ATP
      hydrolysis is essential for the efflux. Verapamil completely inhibited the
      taurocholate-dependent efflux of phospholipids and cholesterol from HEK/ABCB4
      cells. Mass spectrometry revealed that, in the presence of taurocholate,
      HEK/ABCB4 cells preferentially secreted PC compared to sphingomyelin. PC vesicles
      induced cholesterol diffusion from cell membrane, but did not accept cholesterol
      from ABCB4. CONCLUSION: ABCB4 mediates the efflux of phospholipids into the
      canalicular lumen in the presence of bile salts, and plays a crucial role in bile
      formation and lipid homeostasis.

PMID- 17523163
TI  - Antenatal sonographic features of aneurysmal dilatation of a vitelline vein.
AB  - We report a case of aneurysmal dilatation of a vitelline vein observed
      antenatally. Intra-abdominal vascular dilatation was diagnosed on ultrasound
      examination at 24 weeks' gestation. The relationship with the umbilicus and
      portal vein suggested the diagnosis of umbilical vein varix. Fetal tolerance
      remained excellent in spite of a gradual increase in the size of the dilated
      vein. Postnatal ultrasound examination revealed thrombosis of the aneurysm with
      gradual extension to the portal vein and the onset of serious coagulation
      problems. Operative findings on postnatal day 9 included the absence of intra
      abdominal umbilical vein, and the presence of an abnormal, dilated and thrombosed
      vein connecting the umbilicus to the portal vein and following the trajectory of
      the right vitelline vein. Corrective surgery was attempted by resection of the
      aneurysm and portal thrombectomy, but this did not prevent the development of
      portal obstruction syndrome with cavernous hemangioma. This anomaly, in which the
      fetal venous return uses the vitelline vein in the absence of the umbilical vein,
      does not appear to have been described before. The mechanism in question could be
      anastomosis between the right vitelline vein and umbilical vein. Antenatal
      diagnosis should enable early surgical management before the formation of a
      portal thrombosis.

PMID- 17523164
TI  - Standardization of three-dimensional images in obstetrics and gynecology:
      consensus statement.
AB  - Standardization of the display of ultrasound images has so far only been achieved
      in transabdominal two-dimensional (2D) sonography. In contrast, there is a lack
      of uniformity in the demonstration of transvaginal 2D ultrasound images. The
      described non-uniformity frequently leads to confusion in the assessment of an
      image, in particular with regard to the accurate anatomical assignment of
      left/right and dorsal/ventral. Three-dimensional (3D) sonography offers a unique
      opportunity to avoid this confusion in the interpretation of ultrasound images,
      because, independent of primary volume acquisition, the volume can always be
      rotated so that the stored object can at all times be visualized in a known
      anatomical position, rendering it of no importance whether the image acquired
      transvaginally is demonstrated from above or from below. This will also be
      important in allowing fusion of ultrasound image data with computed tomographic,
      magnetic resonance and/or positron emission tomography images. In this article we
      suggest that standardization of transabdominal and transvaginal 3D images does
      not only provide the inexperienced physician/sonographer with a guide to spatial
      orientation, but also serves to avoid erroneous topographical interpretations.

PMID- 17523165
TI  - Assessment of circadian rhythms throughout the menstrual cycle of female rhesus
      monkeys.
AB  - Reproductive cyclicity has a significant influence on the regulation of circadian
      rhythms in rodents. Studies have suggested that there are changes in body
      temperature rhythms between the follicular and luteal phases in human females.
      This study examined the effects of menstrual cyclicity on physiological and
      behavioral circadian rhythms in female rhesus monkeys (Macaca mulatta), an
      acknowledged biomedical model. Seven unrestrained subjects were implanted with a
      biotelemetry transmitter to measure body temperature and heart rate and an
      accelerometer was used to measure physical activity. Water was available ad
      libitum and drinking was measured via an electronic circuit attached to a water
      lixit. A video-based task system, the Psychomotor Test System, provided
      environmental enrichment and delivered a pelletized diet. Mean, phase, and
      amplitude of each rhythm were calculated. Estrogen and progesterone conjugates
      were assayed and quantified from daily urine samples to identify follicular and
      luteal phases of the menstrual cycle. Average circadian variables were then
      compared between these phases. Heart rate was significantly (P< or =0.05) delayed
      in the luteal phase. Albeit non-significant, analysis showed a trend toward
      decreased circadian amplitude of body temperature in the luteal phase.

PMID- 17523166
TI  - Single-droplet evaporation kinetics and particle formation in an acoustic
      levitator. Part 2: drying kinetics and particle formation from microdroplets of
      aqueous mannitol, trehalose, or catalase.
AB  - A single droplet drying acoustic levitator has been used to examine the drying
      behavior of droplets of pharmaceutically relevant solutes used to produce protein
      loaded particles via spray-drying. The drying behavior of solution droplets of
      mannitol, trehalose, or catalase was determined. Evidence of super-saturation of
      the solute in the droplet surface up to the critical point of drying was
      obtained. The trehalose achieves a lower degree of super-saturation than does the
      mannitol before precipitating at the droplet surface. This results in a shorter
      duration of the constant-rate period, but protracted further drying of this
      amorphous material. Mannitol achieved a higher degree of super-saturation, and a
      later critical point with shorter falling-rate period. Measurements of dried
      particle radius showed that both solutes form hollow particles. The catalase
      formed holed, hollow particles with characteristic drying rate profiles that
      correlated well with developing particle morphology. A strong similarity between
      the morphologies of dried particles of mannitol, trehalose, or catalase produced
      either in the levitator or in a spray-dryer was found.

PMID- 17523167
TI  - Mechanisms of nitric oxide-induced apoptosis in bovine chromaffin cells: Role of
      mitochondria and apoptotic proteins.
AB  - The aim of this work was to establish the possible involvement of mitochondria in
      the apoptotic event triggered by nitric oxide (NO) in chromaffin cells. Using
      bovine chromaffin cells in primary culture and several NO donors (SNP, SNAP, and
      GSNO) at apoptotic concentrations (50 microM-1 mM), we have shown that NO induces
      a time-dependent decrease in the mitochondrial transmembrane potential
      (DeltaPsi(m)), which correlates with the appearance of hypodiploid cells.
      Disruption in DeltaPsi(m) is followed by cytochrome c release to the cytosol,
      which in turn precedes caspase 3 activation. In this mechanism participates the
      Bcl-2 protein family, because NO donors downregulate the expression of anti
      apoptotic members of the family such as Bcl-2 and Bcl-XL, and increase the
      expression of pro-apoptotic members, Bax and Bcl-Xs, inductors of cytochrome c
      release to cytosol. Different cell signaling pathways seem to regulate Bax
      induction and Bcl-2 inhibition because decreased Bcl-2 levels are detected later
      than enhanced Bax expression. The tumour suppressor protein p53 is also
      upregulated in a very early phase (30 min) of the NO-induced apoptosis and may be
      responsible for the further induction of Bax expression. Finally, the
      translocation of NF-kappaB to the nucleus seems to be another early event in NO
      induced apoptosis and it may be involved in the regulation of p53 expression.
      These results support strongly the participation of mitochondrial mechanisms in
      NO-induced apoptosis in chromaffin cells and suggest that these cells may be good
      models for the investigation of molecular basis of neurodegeneration and
      neuroprotection.

PMID- 17523168
TI  - Immunohistochemical characterization of periodontal wound healing following
      nonsurgical treatment with fluorescence controlled Er:YAG laser radiation in
      dogs.
AB  - BACKGROUND AND OBJECTIVE: The aim of the present study was to
      immunohistochemically characterize periodontal wound healing following
      nonsurgical treatment with fluorescence controlled Er:YAG laser radiation in
      dogs. STUDY DESIGN/MATERIALS AND METHODS: Five beagle dogs suffering from
      naturally occurring chronic periodontitis were randomly allocated in a split
      mouth design to nonsurgical periodontal treatment using either (a) an Er:YAG
      laser at 10.2, 12.8, 15.4, 18, and 20.4 J/cm2 (ERL1-5), or (b) an ultrasonic
      device (VUS) serving as control. The animals were sacrificed after 3 months.
      Histomorphometrical (e.g. inflammatory cell infiltrate, surface changes, cementum
      formation), and immunohistochemical parameters (collagen type I, CD68, matrix
      metalloproteinase (MMP)-8) were assessed. RESULTS: Inflammatory cell infiltrates
      of different extent were commonly observed in all treatment groups. However,
      histomorphometrical analysis revealed new cementum formation with inserting
      collagen type I fibers along the instrumented root surfaces in most specimens of
      both ERL (ERL2: 31+/-81 to ERL5: 595+/-575 microm) and VUS (50+/- 215 microm)
      groups. This was associated with pronounced CD68 and weak MMP-8 antigen
      reactivity. CONCLUSION: Within the limits of the present study, it was concluded
      that both treatment procedures (i) were effective in controlling inflammatory
      cell infiltrates, and (ii) may support the formation of a new connective tissue
      attachment.

PMID- 17523169
TI  - Effect of low-level laser treatment after installation of dental titanium implant
      immunohistochemical study of RANKL, RANK, OPG: an experimental study in rats.
AB  - BACKGROUND AND OBJECTIVES: This experiment using an animal experimental model was
      conducted in order to investigate the effect of low-level laser therapy (LLLT) on
      the healing of the dental titanium implant. STUDY DESIGN/MATERIALS AND METHODS:
      The experimental group received LLLT for a week and the control group did not.
      Each group consisted of 10 rats. Two rats from the groups were euthenized on the
      days 1, 3, 7, 14, and 21 of the experiment. The expression of receptor activator
      of nuclear factor kB ligand (RANKL), osteoprotegerin (OPG), and receptor
      activator of nuclear factor kB (RANK) were investigated. RESULTS: The expression
      of RANKL was observed from the initial stage of the installation of the implant
      for both the experimental and control groups. However, the degree of expression
      was higher in the experimental group. The degree of expression of OPG increased
      remarkably in the experimental group, while in the control group the degree of
      expression increased only slightly. In the experimental group, the expression of
      RANK was observed from the first day, but in the control group, it was weakly
      observed after day 3. The overall expression within the bone was slight on day 7
      in the control group, while an active expression was observed in the experimental
      group. Bone density after installation of dental titanium implant during
      osseointegration in the experimental group was higher than the control group. The
      surface and structure of the titanium implant was not damaged by low-level laser
      (LLL). CONCLUSIONS: From the above results, the expression of OPG, RANKL, and
      RANK during the osseointegration of the dental titanium implant was observed
      within bone tissue. The application of the LLL influenced the expression of OPG,
      RANKL, and RANK, and resulted in the expansion of metabolic bone activity and
      increased the activity of bone tissue cells.

PMID- 17523170
TI  - Effects of ecdysteroid agonist RH-2485 reveal interactions between ecdysteroids
      and juvenile hormones in the development of Sesamia nonagrioides.
AB  - Larvae of Sesamia nonagrioides developing under long day (LD) conditions pupate
      in the 5th or 6th instar, whereas under the short day (SD) conditions, they
      undergo several supernumerary larval molts and are regarded as diapausing. The
      development in early larval instars occurs in the LD larvae at a moderate and in
      the SD larvae at a high juvenile hormone (JH) titer; ecdysteroid titer cycles
      similarly under both conditions. The transformation to pupa is initiated by a
      burst of ecdysteroids at undetectable JH levels, whereas extra larval molts in
      the diapausing larvae are associated with moderate JH titer and irregular rises
      of ecdysteroids. Application of 0.2 ppm RH-2485 to the diet of the 6th instar
      larvae promotes hormonal changes supporting metamorphosis in the LD larvae and
      slightly accelerates larval molts in the diapausing SD larvae. The 0.5- and 1-ppm
      doses revert these patterns of endocrine regulations to a mode typical for early
      larval instars. Particularly dramatic is a JH titer increase provoked within 24 h
      in the LD larvae. After the treatment, both the LD and SD larvae undergo a series
      of larval molts, suggesting that hormonal programming of the larval development
      has been stabilized. A few insects receiving 1 ppm RH-2485, and a high proportion
      of those fed with 5 ppm RH-2485, deposit two cuticles within a single apolysis
      and die.

PMID- 17523171
TI  - Effects of octopamine on reproduction, juvenile hormone metabolism, dopamine, and
      20-hydroxyecdysone contents in Drosophila.
AB  - The effect of an experimentally increased octopamine content (feeding flies with
      OA) on the levels of juvenile hormone (JH) degradation, dopamine (DA), and 20
      hydroxyecdysone (20E) contents, oogenesis, and fecundity of wild type Drosophila
      flies has been studied. OA feeding of the flies was found to (1) cause a
      considerable decrease in JH degradation in females, but not males, of D.
      melanogaster and D. virilis; (2) have no effect on DA content in D. melanogaster
      and D. virilis; (3) increase 20E contents in D. virilis females; (4) decrease to
      a large extent the number of vitellogenic (stages 8-10) and mature (stage 14)
      oocytes in D. virilis; and (5) decrease the fecundity of D. melanogaster and D.
      virilis. A possible mechanism of action of OA as a neurohormone on the
      reproductive function of Drosophila is discussed.

PMID- 17523172
TI  - Dopamine and octopamine regulate 20-hydroxyecdysone level in vivo in Drosophila.
AB  - The effects of increased level of dopamine (DA) (feeding flies with DA precursor,
      L-dihydroxyphenylalanine, L-DOPA) on the level of 20-hydroxyecdysone (20E) and on
      juvenile hormone (JH) metabolism in young (2-day-old) wild type females (the
      strain wt) of Drosophila virilis have been studied. Feeding the flies with L-DOPA
      increased DA content by a factor of 2.5, and led to a considerable increase in
      20E level and a decrease of JH degradation (an increase in JH level). We have
      also measured the levels of 20E in the young (1-day-old) octopamineless females
      of the strain Tbetah(nM18) and in wild type females, Canton S, of D.
      melanogaster. The absence of OA led to a considerable decrease in 20E level
      (earlier it was shown that in the Tbetah(nM18) females, JH degradation was
      sharply increased). We have studied the effects of JH application on 20E level in
      2-day-old wt females of D. virilis and demonstrated that an increase in JH titre
      results in a steep increase of 20E level. The supposition that biogenic amines
      act as intermediary between JH and 20E in the control of Drosophila reproduction
      is discussed.

PMID- 17523173
TI  - Different Ca2+ signalling cascades manifested by mastoparan in the prothoracic
      glands of the tobacco hornworm, Manduca sexta, and the silkworm, Bombyx mori.
AB  - Application of the tetradecapeptide mastoparan to the prothoracic glands (PGs) of
      the tobacco hornworm, Manduca sexta, and the silkworm, Bombyx mori, resulted in
      increases in intracellular Ca(2+) ([Ca(2+)](i)). In M. sexta, Gi proteins are
      involved in the mastoparan-stimulated increase in [Ca(2+)](i). However, there is
      no involvement of Gi proteins in the mastoparan-stimulated increase in
      [Ca(2+)](i) in prothoracic gland cells from B. mori. Unlike in M. sexta
      prothoracic glands, in B. mori prothoracic glands mastoparan increases
      [Ca(2+)](i) even in the absence of extracellular Ca(2+). Pharmacological
      manipulation of the Ca(2+) signalling cascades in the prothoracic glands of both
      insect species suggests that in M. sexta prothoracic glands, mastoparan's first
      site of action is influx of Ca(2+) through plasma membrane Ca(2+) channels while
      in B. mori prothoracic glands, mastoparan's first site of action is mobilization
      of Ca(2+) from intracellular stores. In M. sexta, the combined results indicate
      the presence of mastoparan-sensitive plasma membrane Ca(2+) channels, distinct
      from those activated by prothoracicotropic hormone or the IP(3) signalling
      cascade, that coordinate spatial increases in [Ca(2+)](i) in prothoracic gland
      cells. We propose that in B. mori, mastoparan stimulates Ca(2+) mobilization from
      ryanodine-sensitive intracellular Ca(2+) stores in prothoracic gland cells.

PMID- 17523174
TI  - Diversity of detoxification pathways of ingested ecdysteroids among phytophagous
      insects.
AB  - The metabolic pathways of ingested ecdysteroids have been investigated in three
      insect species, the aphid Myzus persicae and two Lepidoptera, Plodia
      interpunctella and Ostrinia nubilalis. M. persicae produces mainly a 22-glucoside
      conjugate, whereas P. interpunctella eliminates a mixture of 20E and its 3-oxo
      and 3-epi derivatives, both in free form and as conjugates with various fatty
      acids. O. nubilalis only produces fatty acyl ester conjugates. These data point
      out the great diversity of detoxification mechanisms used by phytophagous insects
      in order to overcome the potential harmful effects of ecdysteroids present in
      their food.

PMID- 17523175
TI  - Neural crest cell deficiency of c-myc causes skull and hearing defects.
AB  - The proto-oncogene c-myc has a central role in multiple processes important for
      embryonic development, including cell proliferation, growth, apoptosis, and
      differentiation. We have investigated the role of c-myc in neural crest by using
      Wnt1-Cre-mediated deletion of a conditional mutation of the c-myc gene. c-myc
      deficiency in neural crest resulted in viable adult mice that have defects in
      coat color, skull frontal bone, and middle ear ossicle development. Physiological
      hearing studies demonstrated a significant hearing deficit in the mutant mice. In
      this report, we focus on the craniofacial and hearing defects. To further examine
      neural crest cells affected by c-myc deficiency, we fate mapped Wnt1-Cre
      expressing neural crest cells using the ROSA26 Cre reporter transgene. The
      phenotype obtained demonstrates the critical role that c-myc has in neural crest
      during craniofacial development as well as in providing a model for examining
      human congenital skull defects and deafness.

PMID- 17523177
TI  - Host-induced ecdysteroids in the stop-and-go oogenesis in a synovigenic
      parasitoid wasp.
AB  - Eupelmus vuilleti (Hymenoptera; Eupelmidae) is a solitary ectoparasitoid
      producing yolk-rich eggs. The female oviposits mainly on the fourth larval instar
      of Callosobruchus maculatus (Coleoptera; Bruchidae), which develop within pods
      and seeds of Vigna unguiculata (Fabacae). Parasitoid females are synovigenic,
      i.e., they are born with immature eggs and need to feed from the host to sustain
      egg production during their entire lifetime. However, eggs are rapidly resorbed
      in unfavourable conditions and an efficient stop-and-go mechanism controls
      oogenesis in such animals. In this study, the possible involvement of
      ecdysteroids in the regulation of parasitoid oogenesis is examined. In a first
      step, the identity and titre of ecdysteroids in reproductively active and
      inactive female parasitoids were investigated by high performance liquid
      chromatography followed by enzyme immuno-assay (EIA/HPLC). A larger secretion of
      ecdysone was found in female during their reproductive period compared with
      inactive females. In a second step, both the secretion of ecdysteroids into the
      medium of in vitro incubated ovaries and the ecdysteroid content of females
      reared with or without host were measured (EIA). The presence of the host, which
      represents both the oviposition site and the nutritional source, induced an
      active biosynthesis of ecdysone. This synthesis started at a slow rate after host
      introduction and reached a maximum after 48 h. When hosts were available, this
      synthesis was cyclic and continuous during the entire female lifetime. These
      results showed that host presence triggered ovarian synthesis of ecdysteroids,
      which are involved in a stop-and-go regulation of egg production linked to host
      availability.

PMID- 17523178
TI  - Skin changes following minor trauma.
AB  - BACKGROUND AND OBJECTIVE: Bruises are currently evaluated by visual inspection,
      and little is known about the first phase after injury. The temporal development
      of fresh injuries must be accurately described to be able to age bruises in a
      reliable manner. Color changes in a bruise caused by hemoglobin breakdown
      products will depend on the severity of the trauma, and thus on the local immune
      response in the skin. It is therefore important to relate the nature of the
      impact to the temporal tissue responses. MATERIALS AND METHODS: Controlled
      injuries were inflicted on anesthetized domestic pigs. Trauma was induced either
      by a pendulum device, or by paintballs released using pressurized air. The speed
      of the projectiles was recorded using a high speed camera. Biopsies and
      reflection spectra (400-850 nm) were collected from normal and bruised skin. The
      experiments were approved by the national animal research authority. RESULTS: The
      temporal development of the injury was found to depend strongly on the weight and
      speed of the object. Low speed, blunt objects did not cause persistent skin
      changes. However, deep muscular bleeding could be found in most cases. High
      speed, light weight objects caused a rapidly developing bruise. These bruises
      were fully developed within 15-20 minutes. No deep muscular hemorrhages were
      observed in those cases. White blood cells (neutrophilic granulocytes) could be
      found in biopsies from high speed injuries. The amount of white blood cells
      depended on the time between injury and collection of the biopsies. CONCLUSION:
      Further investigations utilizing a larger range of object weight and velocities
      are required to be able to fully classify minor traumatic injuries. Preliminary
      results indicate that this can be achieved by controlled experiments using a
      porcine model. Reflectance spectroscopy was found to be a useful tool to study
      immediate skin reactions to the trauma.

PMID- 17523179
TI  - Laryngeal schwannoma in an 8-year-old boy with inspiratory dyspnea.
AB  - BACKGROUND: Schwannomas of the larynx are rare lesions in the pediatric age
      group. METHODS: In this article, we report on the neuroimaging features of a
      schwannoma arising from the left aryepiglottic fold in an 8-year-old boy with a 6
      month history of inspiratory dyspnea. RESULTS: Neuroimaging showed a well
      defined, avoid mass originating from the left aryepiglottic fold. The lesion was
      removed endoscopically. CONCLUSION: Complete removal of laryngeal schwannomas is
      curative, and adjuvant treatment is not required.

PMID- 17523180
TI  - Nicotine prevents disruption of the late phase LTP-related molecular cascade in
      adult-onset hypothyroidism.
AB  - We have shown previously that chronic nicotine treatment reverses adult-onset
      hypothyroidism-induced impairment of late-phase long-term potentiation (L-LTP) in
      area CA1 of the hippocampus. In the present study, basal and stimulated levels of
      signaling molecules essential for the expression of L-LTP were determined in area
      CA1. Immunoblots analysis showed that chronic nicotine treatment of hypothyroid
      rats prevented the reduction in the basal protein levels of adenylyl cyclase I
      (ACI), mitogen-activated protein kinases [MAPKp44/42 (ERK1/2)], calcium
      calmodulin-dependent protein kinase IV (CaMKIV), and cyclic-AMP response element
      binding protein [CREB; phosphorylated (P-) and total]. A significant increase in
      the levels of P-CREB, P-MAPKp44, P-MAPKp42 and brain derived neurotrophic factor
      (BDNF) was seen 4 h after multiple train high frequency stimulation (MHFS) in
      nicotine-treated hypothyroid and control animals, but not in hypothyroid animals.
      The levels of total CREB, total MAPKp44, total MAPKp42, and CaMKIV were elevated
      in all groups 4 h after MHFS. These findings suggest that prevention of the
      reduced basal level of CaMKIV, MAPKp44/42, and CREB by nicotine along with the
      regained ability of MHFS to induce MAPKp44/42 and CREB phosphorylation in
      nicotine treated hypothyroid animals may be responsible for the reversal of L-LTP
      impairment by chronic nicotine treatment in this disease model.

PMID- 17523181
TI  - Effects of antipsychotic treatments and D-serine supplementation on the
      electrophysiological activation of midbrain dopamine neurons induced by the
      noncompetitive NMDA antagonist MK 801.
AB  - The acute administration of the noncompetitive glutamate N-methyl-D-aspartate
      (NMDA) receptor antagonist dizocilpine (MK 801) is known to increase central
      dopaminergic activity in rats and to elicit schizophreniform behavior in human.
      The current study was undertaken to compare the effects of different acute or
      chronic neuroleptic treatments, on the response of ventral tegmental area
      dopamine (DA) neurons to MK 801, using the in vivo electrophysiological paradigm
      in anesthetized preparations. Sprague Dawley male rats were treated, acutely or
      chronically during 3 weeks, with saline, olanzapine (10 mg/kg), haloperidol (1
      mg/kg) or the combination of haloperidol with D-serine (1 mg/kg/300 mg/kg), a
      gliotransmitter coagonist of the NMDA receptor that has been shown to improve the
      efficacy of typical neuroleptics. In control animals, the acute administration of
      MK 801 (0.5 mg/kg, i.v.) increased significantly both the firing and burst
      activity of DA neurons by 20 and 26%, respectively, the latter effect being
      partially reversed by the selective 5-HT2A antagonist M 100,907 (0.4 mg/kg,
      i.v.). The acute preadministration of haloperidol (1 mg/kg, i.p.) and olanzapine
      (10 mg/kg, i.p.) failed to prevent or reverse the activatory effect of MK 801 on
      firing activity. On the other hand, MK 801-induced burst activity, was partially
      prevented by olanzapine, but not by haloperidol pretreatment. All antipsychotic
      treatments, when administered chronically, prevent the activatory effect of MK
      801 on both firing and burst activity, and occasionally convert the response to
      MK 801 on burst activity to an inhibitory response, the latter occurring more
      predominantly in rats treated with the combination haloperidol/D-serine. These
      results suggest that a chronic antipsychotic regime alters the function of the
      NMDA receptors that tonically control the firing activity of midbrain
      dopaminergic neurons.

PMID- 17523182
TI  - Dendrimer-entrapped gold nanoparticles as a platform for cancer-cell targeting
      and imaging.
AB  - We present a general approach for the targeting and imaging of cancer cells using
      dendrimer-entrapped gold nanoparticles (Au DENPs). Au DENPs were found to be able
      to covalently link with targeting and imaging ligands for subsequent cancer-cell
      targeting and imaging. The Au DENPs linked with defined numbers of folic acid
      (FA) and fluorescein isothiocyanate (FI) molecules are water soluble, stable, and
      biocompatible. In vitro studies show that the FA- and FI-modified Au DENPs can
      specifically bind to KB cells (a human epithelial carcinoma cell line) that
      overexpress high-affinity folate receptors and they are internalized dominantly
      into lysosomes of target cells within 2 h. These findings demonstrate that Au
      DENPs may serve as a general platform for cancer imaging and therapeutics.

PMID- 17523183
TI  - Alcohol-vapor inclusion in single-crystal adsorbents [M(II)2(bza)4(pyz)]n (M =
      Rh, Cu): structural study and application to separation membranes.
AB  - The vapor absorbency of the series of alcohols methanol, ethanol, 1-propanol, 1
      butanol, and 1-pentanol was characterized on the single-crystal adsorbents
      [M(II)2(bza)4(pyz)]n (bza = benzoate, pyz = pyrazine, M = Rh (1), Cu (2)). The
      crystal structures of all the alcohol inclusions were determined by single
      crystal X-ray crystallography at 90 K. The crystal-phase transition induced by
      guest adsorption occurred in the inclusion crystals except for 1-propanol. A
      hydrogen-bonded dimer of adsorbed alcohol was found in the methanol- and ethanol
      inclusion crystals, which is similar to a previous observation in 2 x 2EtOH (S.
      Takamizawa, T. Saito, T. Akatsuka, E. Nakata, Inorg. Chem. 2005, 44, 1421-1424).
      In contrast, an isolated monomer was present in the channel for 1-propanol, 1
      butanol, and 1-pentanol inclusions. All adsorbed alcohols were stabilized by
      hydrophilic and/or hydrophobic interactions between host and guest. From the
      combined results of microscopic determination (crystal structure) and macroscopic
      observation (gas-adsorption property), the observed transition induced by gas
      adsorption is explained by stepwise inclusion into the individual cavities, which
      is called the "step-loading effect." Alcohol/water separation was attempted by a
      pervaporation technique with microcrystals of 2 dispersed in a
      poly(dimethylsiloxane) membrane. In the alcohol/water separation, the membrane
      showed effective separation ability and gave separation factors (alcohol/water)
      of 5.6 and 4.7 for methanol and ethanol at room temperature, respectively.

PMID- 17523184
TI  - Channelling of SSRIs and SNRIs use in the Tayside population, Scotland.
AB  - PURPOSE: To compare the user profiles of the two classes of drug, using the
      Tayside Medicines Monitoring Unit (MEMO) record-linkage database. METHODS: A
      cohort study was carried out in the population of Tayside in Scotland. A total of
      13 901 selective serotonin re-uptake inhibitor (SSRI) users and 1417 selective
      norepinephrine re-uptake inhibitor (SNRI) users were identified during the period
      of December 2000 to November 2001. A logistic regression model was used to assess
      the association between drug use and patients profiles and a Cox regression model
      was employed to examine the effect of drug use and mortality outcome. RESULTS:
      Compared to SNRI patients, SSRI patients were significantly older (28.8% >/= 60
      year vs. 26.2%), more likely to be female (70.9% vs. 67.8%), had more
      cardiovascular disease history (10.1% vs. 8.5%), but were less deprived (9.7% in
      the highest deprivation category vs. 12.4%), had less digestive disease (27.9%
      vs. 31.0%) and less history of drug overdose hospitalisation (7.2% vs. 11.9%).
      SNRI patients had more drug switching than SSRI patients (62.0% for recent users,
      33.2% for prevalent users vs. 39.1%, 26.1%, respectively). The age-standardised
      mortality rates during the follow-up period until December 2003 were 5.3% for
      SSRI and 5.9% for SNRI users. CONCLUSION: There was clear evidence that SSRI and
      SNRI were used in patient groups with different characteristics. This channelling
      sometimes favoured an improved mortality outcome and sometimes favoured a worse
      outcome. Overall there was no mortality difference between the two classes of
      drugs.

PMID- 17523185
TI  - Reliability evaluation of the adapted national coordinating council medication
      error reporting and prevention (NCC MERP) index.
AB  - PURPOSE: Adapted National Coordinating Council for Medication Error Reporting and
      Prevention (NCC MERP) Index criteria were used in a study undertaken to evaluate
      commercial computerized provider order entry (CPOE) system impact on community
      hospital medication errors. This article describes: (1) adaptation of the Index,
      (2) classification criteria and processes used to assess the adapted Index, and
      (3) inter-rater reliability results. METHODS: A random sample of 130 (17%) of
      2251 medication safety events (MSEs) were classified based on event type, that
      is, adverse drug event (ADE) or potential ADE (PADE); preventability, that is,
      'yes' or 'no,' and outcome severity. Event outcome severity was categorized using
      adapted Index categories E-I (ADEs) and B-D (PADEs). Decision rules were used for
      rule-based classification, while an MSE Case Review Panel used judgment-based
      classification when decision rules did not apply. Inter-rater reliability for
      both classification approaches was assessed with kappa coefficients, percentage
      agreement, and confidence intervals (CI). RESULTS: Level of agreement was
      substantial for both rule-based and judgment-based MSE classification for event
      type (6 = 0.70-0.90), preventability (6 = 0.67-0.82), and decision rule
      application (6 = 0.79). Rule-based agreement for ADE and PADE severity was almost
      perfect for discrete (6 = 0.83-0.84) and combined (6 = 0.87-0.90) Index
      categories. Judgment-based agreement was substantial for discrete (6 = 0.63-0.67)
      and combined (6 = 0.66-0.84) Index categories. CONCLUSIONS: The adapted Index
      yielded substantial agreement for event type, preventability, and severity.
      Adaptation of the Index to support classification of non-preventable ADEs was an
      important improvement.

PMID- 17523186
TI  - The relationship between n-gram patterns and protein secondary structure.
AB  - An n-gram pattern (NP{n,m}) in a protein sequence is a set of n residues and m
      wildcards in a window of size n+m. Each window of n+m amino acids is associated
      with a collection of NP{n,m} patterns based on the combinatorics of n+m objects
      taken m at a time. NP{n,m} patterns that are shared between sequences reflect
      evolutionary relationships. Recently the authors developed an alignment
      independent protein classification algorithm based on shared NP{4,2} patterns
      that compared favorably to PSI-BLAST. Theoretically, NP{4,2} patterns should also
      reflect secondary structure propensity since they contain all possible n-grams
      for 1 < or = n < or = 4 and a window of 6 residues is wide enough to capture
      periodicities in the 2 < or = n < or = 5 range. This sparked interest in
      differentiating the information content in NP{4,2} patterns related to evolution
      from the content related to local propensity. The probability of alpha-, beta-,
      and coil components was determined for every NP{4,2} pattern over all the chains
      in the Protein Data Bank (PDB). An algorithm exclusively based on the Z-values of
      these distributions was developed, which accurately predicted 71-76% of alpha
      helical segments and 62-67% of beta-sheets in rigorous jackknife tests. This
      provided evidence for the strong correlation between NP{4,2} patterns and
      secondary structure. By grouping PDB chains into subsets with increasing levels
      of sequence identity, it was also possible to separate the evolutionary and local
      propensity contributions to the classification process. The results showed that
      information derived from evolutionary relationships was more important for beta
      sheet prediction than alpha-helix prediction.

PMID- 17523187
TI  - From coarse-grain to all-atom: toward multiscale analysis of protein landscapes.
AB  - Multiscale methods are becoming increasingly promising as a way to characterize
      the dynamics of large protein systems on biologically relevant time-scales. The
      underlying assumption in multiscale simulations is that it is possible to move
      reliably between different resolutions. We present a method that efficiently
      generates realistic all-atom protein structures starting from the C(alpha) atom
      positions, as obtained for instance from extensive coarse-grain simulations. The
      method, a reconstruction algorithm for coarse-grain structures (RACOGS), is
      validated by reconstructing ensembles of coarse-grain structures obtained during
      folding simulations of the proteins src-SH3 and S6. The results show that RACOGS
      consistently produces low energy, all-atom structures. A comparison of the free
      energy landscapes calculated using the coarse-grain structures versus the all
      atom structures shows good correspondence and little distortion in the protein
      folding landscape.

PMID- 17523188
TI  - Pactolus I-domain: functional switching of the Rossmann fold.
AB  - Murine Pactolus is a neutrophil-specific single chain glycoprotein that plays a
      role as an apoptosis marker for macrophages. The extracellular region of the
      protein shows strong sequence similarities to integrin beta-subunits. Critical
      sequence modifications differentiate its function when compared to the integrin
      family. We show experimentally that Pactolus I-domain does not bind divalent
      metal ions, indicating that ligand binding is not mediated through a metal ion
      dependent adhesion site (MIDAS). NMR data was used to map secondary structure and
      the strand pairing within the beta-sheet to confirm an overall Rossmann fold
      topology. Homology modeling enhanced by the NMR data was used to determine the
      overall structure, with two key loop insertions/deletions (insertion 2 and SDL)
      that distinguish the Pactolus I-domain from the integrin alpha I-domain and beta
      I-domains. NMR peak exchange broadening is observed due to dimerization,
      correlating to the beta I-domain and beta propeller heterodimerization region
      within the integrin headpiece. Two unique N-linked glycosylation sites (Asn151
      and Asn230) within this region disrupt dimerization and may account for why
      Pactolus is not found to associate with an alpha-subunit. These changes in
      quaternary structure, ligand binding loops, glycosylation, and metal sites
      illustrate how evolution has rapidly and effectively altered key aspects of the
      integrin beta-subunit to derive a protein of novel function on an existing
      protein scaffold.

PMID- 17523189
TI  - Ranking the factors that contribute to protein beta-sheet folding.
AB  - The formation of beta-sheet domains in proteins involves five energetically
      important factors: the formation of networks of hydrogen bonds and hydrophobic
      faces, and the residue propensities, or preferences, to be found at the edges of
      the beta-sheet, to adopt the extended conformation, and to make contact with
      other residues. These relative energy contributions define a potential energy
      function. Here, we show how optimizing this potential energy function reveals the
      formation of hydrophobic faces as the utmost factor. The potential energy
      function was optimized to minimize the Z-scores of the native topologies among
      the exhaustive sets of over 400 different beta-sheets. These results corroborate
      with experimental data that showed the environment of a protein is an important
      modulator of beta-sheet folding. The contact propensities were found to be the
      least important, which could explain the poor predictive power of beta-strand
      alignment methods based on pair-wise contact matrices.

PMID- 17523190
TI  - Solution NMR structure of Escherichia coli ytfP expands the structural coverage
      of the UPF0131 protein domain family.

PMID- 17523191
TI  - SIMPLE estimate of the free energy change due to aliphatic mutations: superior
      predictions based on first principles.
AB  - The bioinformatics revolution of the last decade has been instrumental in the
      development of empirical potentials to quantitatively estimate protein
      interactions for modeling and design. Although computationally efficient, these
      potentials hide most of the relevant thermodynamics in 5-to-40 parameters that
      are fitted against a large experimental database. Here, we revisit this
      longstanding problem and show that a careful consideration of the change in
      hydrophobicity, electrostatics, and configurational entropy between the folded
      and unfolded state of aliphatic point mutations predicts 20-30% less false
      positives and yields more accurate predictions than any published empirical
      energy function. This significant improvement is achieved with essentially no
      free parameters, validating past theoretical and experimental efforts to
      understand the thermodynamics of protein folding. Our first principle analysis
      strongly suggests that both the solute-solute van der Waals interactions in the
      folded state and the electrostatics free energy change of exposed aliphatic
      mutations are almost completely compensated by similar interactions operating in
      the unfolded ensemble. Not surprisingly, the problem of properly accounting for
      the solvent contribution to the free energy of polar and charged group mutations,
      as well as of mutations that disrupt the protein backbone remains open.

PMID- 17523192
TI  - Bladder ultrasound in the evaluation of the efficacy of dextranomer/hyaluronic
      acid injection for treatment of vesicoureteral reflux.
AB  - PURPOSE: To determine whether sonographic examination of subureteral implants
      after endoscopic dextranomer/hyaluronic acid (DHA) injection would help to
      evaluate the efficacy of this method in the treatment of vesicoureteral reflux.
      MATERIALS AND METHODS: Thirty-six patients (49 ureters) who underwent endoscopic
      subureteral DHA injection were evaluated using voiding cystourethrography (VCUG)
      and bladder sonography for a mean duration of 2.1 years (range, 3 months to 6.5
      years) after treatment. Patient records-including the results of VCUG, renal
      sonography, Dimercapto succinic acid (DMSA) scintigraphy, and periodic urinary
      analysis-were also reviewed to determine the outcome of treatment. RESULTS:
      Reflux was corrected in 43/49 (88%) ureters (complete cure in 38, downgrading of
      reflux in 5). No change was noted in 6 (12%) ureters on VCUG. The reflux was
      found to be corrected in 19/22 (86%) ureters, with the implants clearly
      identifiable on sonography. However, reflux was documented in only 3/27 (11%)
      ureters, around which no implant was seen on sonography. CONCLUSION: The
      identification of the implant in the subureteral region by bladder sonography
      correlated with resolution of reflux in the early postinjection period. On the
      other hand, the majority of the implants disappeared on sonography in the long
      term despite correction of reflux. Therefore, we believe that the use of bladder
      sonography is not useful in the evaluation of patients in long-term follow-up.

PMID- 17523193
TI  - Propriospinal myoclonus: utility of magnetic resonance diffusion tensor imaging
      and fiber tracking.
AB  - Propriospinal myoclonus (PSM) is a rare movement disorder characterized by
      involuntary spinal-generated muscular jerks that spread rostrally and caudally to
      other spinally innervated muscles. Most patients have no clear etiology, and
      conventional MRI of the spinal cord is generally normal. Here we report the use
      of magnetic resonance diffusion tensor imaging (DTI) and fiber tracking to detect
      tract-specific abnormalities in a patient with propriospinal myoclonus. As the
      patient had the fragile-X premutation and antithyroid antibodies, spinal cord DTI
      abnormalities may be related to these conditions. Tract-specific analysis may
      provide new insights into the pathophysiology of propriospinal myoclonus.

PMID- 17523194
TI  - Staged unilateral versus bilateral subthalamic nucleus stimulator implantation in
      Parkinson disease.
AB  - In 17 consecutive patients with Parkinson disease (PD), bilateral subthalamic
      nucleus (STN) stimulators were implanted during staged surgeries. The Unified
      Parkinson Disease Rating Scale (UPDRS) and the Dyskinesia Disability Scale were
      completed both off and on medication prior to any surgery and also OFF and ON
      stimulation after each surgery. On-medication UPDRS activities of daily living
      (ADL) and motor examination scores changed little with unilateral or bilateral
      stimulation. Off-medication UPDRS motor examination scores improved to similar
      degrees after each staged STN electrode implantation. Most of the improvements in
      off-medication ADL scores, dyskinesia scores, complications of therapy, and
      medication dose reduction occurred after unilateral STN stimulation with smaller
      improvements after the second operation.

PMID- 17523195
TI  - Bowel movement frequency in late-life and incidental Lewy bodies.
AB  - It is not known if constipation is associated with the preclinical phase of
      Parkinson's disease (PD), often characterized by the presence of incidental Lewy
      bodies (ILB). Such an association could provide evidence that constipation is an
      early symptom of PD. The purpose of this report is to examine the association
      between late-life bowel movement frequency and ILB. Bowel movement frequency was
      assessed from 1991 to 1993 in 245 men aged 71 to 93 years in the Honolulu-Asia
      Aging Study who later received postmortem examinations. All were without clinical
      PD and dementia. Brains were examined for ILB in the substantia nigra and locus
      ceruleus. Among the decedents, 30 men had ILB (12.2%). After age-adjustment, the
      percent of brains with ILB declined with increasing bowel movement frequency
      (P=0.013). For men with <1, 1, and >1 bowel movement/day, corresponding percents
      were 24.1, 13.5, and 6.5%. Findings persisted after additional adjustment for
      time to death, mid-life pack-years of smoking and coffee intake, physical
      activity, and cognitive function. Infrequent bowel movements are associated with
      ILB. Findings provide evidence that constipation can predate the extrapyramidal
      signs of PD. Constipation could be one of the earliest markers of the beginning
      of PD processes.

PMID- 17523196
TI  - Asymmetric corticomotor excitability correlations in early Parkinson's disease.
AB  - We studied corticomotor excitability (CE) between the more and less affected
      sides in early Parkinson's disease (PD) patients using transcranial magnetic
      stimulation (TMS). Sixteen-PD patients within the first 3 years of diagnosis were
      studied with single-pulse TMS over each motor cortex with intensities from 40% to
      100% stimulator output. Active motor evoked potentials (MEP) and cortical silent
      period durations (CSP) were recorded, fitted with sigmoid curves, summarized as
      maximal MEP/CSP, maximal MEP/CSP slope, and intensity where MEP/CSP is half
      maximal (MEP/CSP-Int50), and correlated with Unified Parkinson's Disease Rating
      Scale scores (UPDRS). On the more affected side, higher (worse) UPDRS scores were
      correlated with shorter maximal CSP (r=-0.51, P=0.046). On the less affected
      side, higher UPDRS scores were correlated with higher MEP-Int50 (r=0.51, P=0.043)
      and CSP-Int50 (r=0.54, P=0.029). For the less affected side, altered CE, as
      indexed by higher MEP or CSP-Int50 intensities, may contribute to early clinical
      symptoms. On the more affected side, increases in CE, indexed by shorter CSP, may
      account for a greater proportion of PD symptoms. These findings are consistent
      with an evolution of neurophysiologic correlates in early PD patients from a less
      to more symptomatic state.

PMID- 17523197
TI  - Decision-making in Parkinson's disease.

PMID- 17523198
TI  - Quality of life and related concepts in Parkinson's disease: a systematic review.
AB  - Several studies have investigated the quality of life (QOL) of patients with
      Parkinson's disease (PD). The purpose of this study was to review the conceptual
      and methodological quality of quality of life (QOL) studies among patients with
      PD and to identify factors associated with poor (HR)QOL. Computerized
      bibliographic databases were screened for publications from 1960 to January 2007.
      According to a list of predefined criteria, the methodological quality of the 61
      studies, was moderate. The term 'QOL' was often used inappropriately. In fact,
      almost all studies in this review actually assessed health status (HS) instead of
      QOL. The functioning of patients with PD on physical, social, and emotional
      domains is affected by PD. Their HS seems to be lower when compared to healthy
      persons or patients with other chronic diseases. HS studies augment the insight
      in self-perceived functioning. Therefore, HS is conceived as a valuable
      construct. However, QOL is also an important factor in health care. Attention
      towards QOL is needed in order to draw valid conclusions regarding a person's
      subjective experience of well-being in a broad sense. In order to accomplish
      this, future studies should apply the QOL concept with more rigor, should use an
      adequate operational definition, and should employ sound measures.

PMID- 17523199
TI  - A novel LRRK2 mutation in an Austrian cohort of patients with Parkinson's
      disease.
AB  - To investigate the frequency of mutations in the Leucine-Rich Repeat Kinase 2
      gene (LRRK2) in a sample of Austrian Parkinson's disease (PD) patients, we
      sequenced the complete coding region in 16 patients with autosomal dominant PD.
      Furthermore, we sequenced exons 31, 35, and 41 additionally in 146 patients with
      idiopathic PD and 30 patients with dementia with Lewy bodies. Furthermore, all
      192 patients were screened for 21 putative LRRK2 mutations. While the most common
      mutation G2019S and the risk variant G2385R were not found in our samples, we
      detected a novel missense mutation (S973N) in a patient with familial, late-onset
      and dopa-responsive PD.

PMID- 17523200
TI  - F centers versus dimer vacancies on ZnO surfaces: characterization by STM and STS
      calculations.

PMID- 17523201
TI  - Formation of an aza-nickelacycle by reaction of an imine and an alkyne with
      nickel(0): oxidative cyclization, insertion, and reductive elimination.

PMID- 17523202
TI  - Trimeric clusters of silver in aqueous AgNO3 solutions and their role as nuclei
      in forming triangular nanoplates of silver.

PMID- 17523203
TI  - Second-order Jahn-Teller effect in a host-guest complex.

PMID- 17523204
TI  - Organocatalytic Highly enantioselective alpha-arylation of beta-ketoesters.

PMID- 17523205
TI  - N-phosphino sulfinamide ligands: an efficient manner to combine sulfur chirality
      and phosphorus coordination behavior.

PMID- 17523206
TI  - Hierarchical self-assembly of one-dimensional streptavidin bundles as a collagen
      mimetic for the biomineralization of calcite.

PMID- 17523207
TI  - Total synthesis of cruentaren A.

PMID- 17523208
TI  - Total synthesis and revised structure of biyouyanagin A.

PMID- 17523211
TI  - Back to the future--defining NK cells and T cells.
AB  - In this issue of the European Journal of Immunology (EJI), Stewart et al. report
      about a population of gammadelta-T cells expressing an extensive repertoire of NK
      cell receptors, and the presence of non-rearranged germline TCRdelta transcripts
      in conventional NK cells. These findings and other recent studies highlight the
      similarities of NK cells and T cells and the problems in discriminating between
      these two lineages.

PMID- 17523212
TI  - Absence of functional alternative complement pathway alleviates lupus cerebritis.
AB  - The complement inhibitor, Crry, which blocks both the classical and alternative
      pathways, alleviates CNS disease in the lupus model, MRL/MpJ-Tnfrsf6lpr (MRL/lpr)
      mice. To understand the role of the alternative pathway, we studied mice
      deficient in a key alternative pathway protein, complement factor B (fB). Immune
      deposits (IgG and C3) were reduced in the brains of MRL/lpr fB-deficient (fB-/
      MRL/lpr) compared to fB-sufficient (MRL/lpr) mice, indicating reduced complement
      activation. Reduced neutrophil infiltration (22% of MRL/lpr mice) and apoptosis
      (caspase-3 activity was reduced to 33% of MRL/lpr mice) in these mice indicates
      that the absence of the alternative pathway was neuroprotective. Furthermore,
      expression of phospho (p)-Akt (0.16+/-0.02 vs. 0.35+/-0.13, p<0.03) was
      increased, while expression of p-PTEN (0.40+/-0.06 vs. 0.11+/-0.07, p<0.05) was
      decreased in fB-/-MRL/lpr mice compared to their MRL/lpr counterparts. The
      expression of fibronectin, laminin and collagen IV was significantly decreased in
      fB-/-MRL/lpr mice compared to MRL/lpr mice, indicating that in the lupus setting,
      tissue integrity was maintained in the absence of the alternative pathway.
      Absence of fB reduced behavioral alterations in MRL/lpr mice. Our results suggest
      that in lupus, the alternative pathway may be the key mechanism through which
      complement activation occurs in brain, and therefore it might serve as a
      therapeutic target for lupus cerebritis.

PMID- 17523213
TI  - Highly restricted diversity of TCR delta chains of the amphibian Mexican axolotl
      (Ambystoma mexicanum) in peripheral tissues.
AB  - Gammadelta T cells localize at mammalian epithelial surfaces to exert both
      protective and regulatory roles in response to infections. We have previously
      characterized the Mexican axolotl (Ambystoma mexicanum) T cell receptor delta
      (TRD) chain. In this study, TRD repertoires in spleen, liver, intestine and skin
      from larvae, pre-adult and adult axolotls were examined and compared to the
      thymic TRD repertoire. A TRDV transcript without N/D diversity, TRDV1S1-TRDJ1,
      dominates the TRD repertoires until sexual maturation. In adult tissues, this
      canonical transcript is replaced by another dominant TRDV1S1-TRDJ1 transcript. In
      the thymus, these two transcripts are detected early in development. Our results
      suggest that gammadelta T cells that express the canonical TRDV1S1-TRDJ1
      transcript emerge from the thymus and colonize the peripheral tissues, where they
      are selectively expanded by recurrent ligands. This particular situation is
      probably related to the neotenic state and the slow development of the axolotl.
      In thymectomized axolotls, TRD repertoires appear different from those of normal
      axolotls, suggesting that extrathymic gammadelta T cell differentiation could
      occur. Gene expression analysis showed the importance of the gut in T cell
      development.

PMID- 17523214
TI  - Electron ionization mass spectra of ephedrines in a doping confirmatory
      procedure: a curious migration of the trimethylsilyl group in the N-acetyl-O
      trimethylsilyl derivatives.
AB  - Ephedrines have central nervous system stimulating properties and, for this
      reason, some of them are forbidden in sport by the World Antidoping Agency
      (WADA). They are screened and quantitated in urine by several published
      techniques and confirmed by gas chromatography/mass spectrometry (GC/MS). In this
      paper, a simple confirmation procedure for norpseudoephedrine, norephedrine,
      ephedrine and pseudoephedrine in human urine by GC/electron ionization (EI)-MS is
      described. After the addition of levallorphane as internal standard, a liquid
      liquid extraction procedure under alkaline conditions with tert-butyl methyl
      ether was applied to the samples. The analytes were derivatized with acetic acid
      anhydride and N-methyl-N-trimethylsilyltrifluoroacetamide to form N-acetyl-O
      trimethylsilyl derivatives. The EI mass spectra of all the studied substances
      have many diagnostic ions with relative abundance in accordance with WADA
      requirements and show great structural information content. A curious migration
      of the trimethylsilyl group is proposed.

PMID- 17523215
TI  - A doctor talks about the periodic health exam.

PMID- 17523216
TI  - [WHO for more health personnel].

PMID- 17523217
TI  - Places responsibility for funding of neutering on owners.

PMID- 17523218
TI  - TDA Awards Committee.

PMID- 17523219
TI  - UK battle over hybrid stem cells.

PMID- 17523220
TI  - Paul Falkowski.

PMID- 17523221
TI  - Tony Blair's legacy for the UK's National Health Service.

PMID- 17523222
TI  - Detection of 36Cl in nuclear reactor waste.

PMID- 17523223
TI  - Estracting pharmaceuticals from fish tissue.

PMID- 17523224
TI  - To trap or transmit, that is the question...

PMID- 17523225
TI  - Revisiting liquid staionary phases.

PMID- 17523226
TI  - The new DEAL: a novel protein display technology captures DNA, proteins, and
      cells on the same microfluidic chip.

PMID- 17523227
TI  - What made the rain red in India? Isotopic analysis points to a terrestrial origin
      for the unusual organic particles that colored the rain like blood.

PMID- 17523228
TI  - When PDMS isn't the best. What are its weaknesses, and which other polymers can
      researchers add to their toolboxes?

PMID- 17523229
TI  - A new look at the selectivity of RPC columns. The hydrophobic subtraction model
      evaluates the selectivity of HPLC reversed-phased columns so that researchers can
      choose a suitable substitute or a sufficiently orthogonal second column.

PMID- 17523230
TI  - Thinking thin for molecular filtration. Ultrathin silicon membranes offer fast,
      effective sorting and separation.

PMID- 17523232
TI  - Product recalls. Recalls: children's necklaces sold at Claire's
      stores...children's mood necklaces...and BABYBJORN Feeding Spoons.

PMID- 17523231
TI  - Seafood in pregnancy: good or bad for the offspring?

PMID- 17523233
TI  - Pioneers in cardiology: Peter Sleight, FRCP, MD. Interview by Jennifer Taylor.

PMID- 17523234
TI  - Heart transplantation in Turkey. Interview by Judy Ozkan.

PMID- 17523235
TI  - [Dissociative symptoms during treatment of borderline personality disorder].
AB  - There are hints for a negative predictive power of dissociative states for
      treatment outcome in patients with borderline personality disorder. A possible
      explanation is the alteration of information processing associated with
      dissociation. Dissociative states can be influenced by specific psychotherapeutic
      interventions. 30 patients with borderline personality disorder were assessed
      with self-report questionnaires to evaluate dissociation and psychopathology
      before and after treatment with Dialectic Behavior Therapy. As found in recent
      studies, dissociation before treatment was correlated to general psychopathology
      at treatment end. In contrast to the core hypothesis, patients with high initial
      dissociation did not present less improvement than those with lower initial
      degrees regarding the parameters of general psychopathology, anxiety, depression
      and psychosocial functioning. In terms of the parameter of dissociation, patients
      with high degrees of initial dissociation even achieved the highest extent of
      relative symptom reduction. This astonishing result can be explained by the
      treatment setting which to a high extent provided specific psychoeducation and
      treatment concerning dissociative behavior.

PMID- 17523236
TI  - Bibliography. Current world literature. Neuropsychiatry.

PMID- 17523237
TI  - [Epileptogenic effects of sevoflurane: new findings].

PMID- 17523238
TI  - Hormones and breast cancer: controlling the danger within.

PMID- 17523239
TI  - Is angioedema a class adverse effect of the angiotensin-converting enzyme
      inhibitors?

PMID- 17523240
TI  - Overview of the Coast Guard Yard's valiant efforts to reduce blood lead levels.

PMID- 17523241
TI  - Mnemonic to aid in recalling the core (A, B, C, D, E) DSM-IV-TR criteria.

PMID- 17523242
TI  - 'The sufficiency of hope'.

PMID- 17523243
TI  - 48-week study results show DRV's staying power.

PMID- 17523244
TI  - Delaying maternal NVP-based ART more effective.

PMID- 17523245
TI  - Frequent methamphetamine use, primary NNRTI resistance.

PMID- 17523246
TI  - Focus on hepatitis. HIV/HCV coinfection and CVD risk.

PMID- 17523248
TI  - Prescription for a healthy journal.

PMID- 17523247
TI  - Effects of salinity and hypoxia on cadmium bioaccumulation in the shrimp Palaemon
      longirostris.
AB  - The aim of the present study was to investigate the role of two key environmental
      factors of estuarine ecosystems, salinity and hypoxia, on the Cd bioaccumulation
      by direct exposure in the white shrimp Palaemon longirostris. Two types of
      experiments were performed in the laboratory. First, we studied Cd accumulation
      by shrimp after metal exposure at two salinities (0.2 and 10 per thousand) and/or
      water oxygen levels (21 and 6 kPa). We also investigated the role of hypoxia in
      more detail and, in particular, its interaction with water Cd concentration by
      subjecting shrimp at low salinity (0.2 per thousand) to two oxygen levels (21 and
      6 kPa) and four concentrations of dissolved Cd metal (0.2, 0.5, 2, and 10
      microg/L). Second, we studied the ventilatory and circulatory responses of P.
      longirostris to changes in oxygen and Cd concentrations to understand some basic
      aspects of the underlying mechanisms involved in the accumulation process. Our
      findings allow us to confirm that salinity is the main factor acting on dissolved
      Cd bioaccumulation processes. However, we demonstrate that hypoxia also must be
      classified as being of primary importance. Through its physiological effect on
      the prawn, hypoxia strongly enhances the rate of Cd accumulation in gills and
      hepatopancreas. Its magnitude is inversely related to the metal concentration,
      because its influence increases when the metal concentration is low. Our results
      show that chemical speciation is, indeed, the primary factor that influences
      metal contamination. On the other hand, at low salinity, under conditions in
      which metal bioavailability is increased, we show that ventilation modifies metal
      accumulation in the gills by a factor of two.

PMID- 17523249
TI  - Engaging students in PLoS Medicine.

PMID- 17523250
TI  - Tackling publication bias in clinical trial reporting. PLoS announces the launch
      of a new online journal.

PMID- 17523251
TI  - Ich Weiss Nicht Was Soll Es Bedeuten: language matters in medicine.

PMID- 17523252
TI  - Social medicine in the twenty-first century.

PMID- 17523253
TI  - One year of PLoS Computational Biology.

PMID- 17523254
TI  - "Editors of the Lancet to the editors of Serbia" and workshop "How to write a
      scientific paper." 8-9 December 2006, Belgrade, Serbia.

PMID- 17523255
TI  - The fourth estate and specialty hospitals.

PMID- 17523256
TI  - What happens to the public interest when medical care becomes a business?

PMID- 17523257
TI  - Controversies in lower-extremity amputation.

PMID- 17523258
TI  - Docs in ads: friends or faux?

PMID- 17523259
TI  - Contact lenses: eying the risks.

PMID- 17523260
TI  - Your memory: 5 ways to keep it sharp.

PMID- 17523261
TI  - Flu 101.

PMID- 17523262
TI  - Kids in need: immediate psychological support for children after a disaster.

PMID- 17523263
TI  - Measures of impact.

PMID- 17523265
TI  - Science in the news.

PMID- 17523264
TI  - Published and not perished.

PMID- 17523266
TI  - ONE for all: the next step for PLoS.

PMID- 17523267
TI  - Molecular mechanisms associated with aggressiveness of alpha-fetoprotein-positive
      gastric cancer.

PMID- 17523268
TI  - Comparison of quality of life between two biliary drainage procedures in
      laparoscopic common bile duct exploration.
AB  - BACKGROUND/AIMS: With various kinds of minimal access surgery being introduced,
      quality of life must be considered as a measure of whether minimal access surgery
      is good or not. We evaluate the difference in quality of life using two kinds of
      biliary drainage procedures in laparoscopic common bile duct exploration.
      METHODOLOGY: Forty cases of laparoscopic common bile duct exploration with
      cholecystectomy were studied to compare gastrointestinal quality of life index
      (GIQLI) preoperatively and postoperatively at two, five and sixteen weeks in two
      groups using different biliary drainage procedures. RESULTS: There was no
      preoperative GIQLI difference between the two groups. Cases with biliary drainage
      through the cystic duct achieved earlier recovery. GIQLI of all cases reached
      normal sixteen weeks postoperatively. CONCLUSIONS: Biliary drainage through the
      cystic duct in laparoscopic common bile duct exploration may help to improve the
      postoperative GIQLI in patients.

PMID- 17523269
TI  - Individualized treatment models based on blood supply characteristics in
      hepatocellular carcinoma using color Doppler hemodynamics.
AB  - BACKGROUND/AIMS: We evaluated the long-term efficacy of the combination of
      transcatheter arterial chemoembolization (TACE) using cisplatin-lipiodol
      suspension, transultrasonic portal vein chemoembolization (SPVE), radiofrequency
      ablation (RF), percutaneous ethanol injection (PEI) for treatment of advanced
      small hepatocellular carcinoma (HCC). METHODOLOGY: A total of three hundred and
      eighteen patients with HCC were enrolled in this study. According to the blood
      supply characteristics to the tumor, individual combined therapy models were
      adopted: one hundred and fifty-nine patients with HCC less than 5 cm were treated
      with a combination of RF and PEI (RF/PEI group) and one hundred and one patients
      with HCC greater than 5cm were treated with a combination of TACE, RF and PEI
      (TACE/RF/PEI group). One hundred and eleven HCC nodules confirmed to be
      hypervascular by color Doppler flow imaging were treated with a combination of
      TACE, RF, SPVE and PEI (TACE/ RF/SPVE/PEI group). RESULTS: The combination
      treatment of RF and PEI (RF/PEI group), the TACE/RF/PEI group, TACE/ RF/SPVE/PEI
      group, the 1-year survival rates and the 3-year survival rates were 97.3% and
      82.4%; 73.5% and 44.9%; 74.1% and 37.9%, respectively; The vanishing rate of
      blood flow around and within the tumor, the tumor size decrease rate, AFP
      transformed to negative rate, were significantly raised compared to those in the
      TACE treatment only group. CONCLUSIONS: The individual combined therapy models
      combination of TACE, PEI, SPVE, RF appears to prolong survival, compared with one
      treatment alone (TACE). This combination therapy method is an effective way for
      treating HCC, and color Doppler can provide important information to verify the
      therapeutic effects.

PMID- 17523270
TI  - Effects of cholecystectomy (laparoscopic versus open) on PMN-elastase.
AB  - BACKGROUND/AIMS: Polymorphonuclear leukocytes (PMN) are well recognized as being
      the principal cells in inflammatory response reaction. During the surgical
      procedures there is a massive release of elastase (PMN-elastase) from the
      neutrophils, along with other proteinases. Therefore the measurement of the PMN
      elastase might be a useful indicator of the degree of surgical trauma.
      Laparoscopic cholecystectomy (LC) is a so-called "mini-invasive" surgical
      procedure and on the basis of this consideration the aim of the present
      prospective, non-randomized study, is to examine (a) whether the serum levels of
      PMN-elastase concentration are modified and how, in patients undergoing LC
      compared to patients undergoing open cholecystectomy (OC), (b) whether these
      findings are indicative of an increased risk to develop infectious complications
      and therefore whether they are clinically significant. METHODOLOGY: Plasma
      granulocyte elastase was determined photometrically, using an immune-activation
      immunoassay, in 86 patients (42 patients underwent OC and 44 LC). The levels of C
      reactive protein (CRP), an acute phase protein, were measured using a competitive
      CRP ELISA kit. Blood samples were collected from all patients a day before
      operation and at days 1, 3, 6 and 12 after operation. We established a reference
      range for elastase by measuring the serum elastase concentration in 68 normal
      control patients without gallbladder cholelithiasis or other diseases. RESULTS:
      On day, 1, 3 and 6 after surgery, patients that underwent OC showed a significant
      increase (p < 0.05) in plasma elastase concentration, while it was almost
      unchanged in LC patients. The mean values of the serum CRP on p.o. days 1, 3 and
      6 were also significantly lower in the LC group than those in OC group (p <
      0.05). We recorded three cases (7.1%) of postoperative infections in the "open"
      group. The CRP concentration remained high for 1, 3 and 6 days and normalized 10
      12 days after surgery while the PMN-elastase normalized after 13, 14 and 16 days.
      CONCLUSIONS: The peripheral leukocyte function may be better preserved after LC
      in comparison to OC. Laparoscopic surgery, associated with a small skin incision
      and the avoidance of open laparotomy, can thus minimize surgical stress, and
      provide more favorable postoperative conditions for patients. Indeed excessive
      and prolonged post-injury elevations of PMN-elastase and CRP are associated with
      increased morbidity. Moreover, the PMN-elastase is a more sensible marker of
      inflammation in comparison to the CRP.

PMID- 17523271
TI  - Hepatopancreatoduodenectomy could be allowed for patients with advanced
      intrahepatic cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Patients with advanced intrahepatic cholangiocarcinoma (ICC)
      have a poor outcome even if they undergo extended radical surgery.
      Hepatopancreatoduodenectomy (HPD; hepatectomy with pancreatoduodenectomy) for
      ICCs may be expected to provide a favorable outcome if curative resection is
      reasonable and patients can tolerate the radical major procedure. METHODOLOGY:
      Between January 1981 and March 2002, 152 hepatic resections were performed for
      ICC. Of these, 12 patients underwent HPD for ICC at the same institute of
      Gastroenterology, Tokyo Women's Medical University. HPD for ICC was indicated in
      patients who (1) require dissection of the peripancreatic lymph nodes, (2)
      exhibit direct invasion of intrapancreatic bile duct, (3) show signs of
      intrapancreatic bile ductal growth. RESULTS: Characteristics of the short-term
      survivors (died within 12 months), compared with long-term survivors (survived
      more than 12 months), indicated that they were more likely to be positive
      intrahepatic metastasis, to be positive lymph node metastasis, to be positive
      portal venous invasion, and margins of resected surface with residual tumor. The
      actuarial overall 1-, 3-, 5-, 10-year survival rates were 42%, 33%, 33%, and 23%,
      respectively. The 5-year survival rate in patients without lymph node metastasis
      was significantly better (p = 0.045) than that of patients with lymph node
      metastasis. The patients who underwent potentially curative resection had
      significantly better 5-year survival rates than those who underwent non-curative
      resection. Four patients survived for at least 5 years and two of these patients
      survived for more than 10 years. Nine patients developed recurrence after
      resection, and of these, 5 patients with recurrence died within 12 months after
      surgery. CONCLUSIONS: HPD is considered to be an efficacious procedure for
      advanced ICC and long-term survival may be possible in a selected group of
      patients.

PMID- 17523272
TI  - Radical surgery for advanced squamous cell carcinoma of the gallbladder: a report
      of three cases, including a 10-year survivor.
AB  - We report three patients who underwent radical resections for advanced squamous
      cell carcinoma of the gallbladder, two of whom are still alive without recurrence
      10 and 9 years after surgery. The other patient, who had lymph node involvement,
      suffered recurrence of the disease and died 9 months after surgery. Our
      experience indicates that radical surgery can sometimes provide a chance for long
      term survival in patients with this neoplasm. Lymph node metastasis, albeit a
      rare event, might be a poor prognostic factor in patients with this type of
      gallbladder carcinoma.

PMID- 17523273
TI  - Candiduria in critically ill patients: an early candidemia marker when coupled
      with multiple blood specimens PCR assays?
AB  - BACKGROUND/AIMS: Can repeated blood PCR assays in critically ill patients with
      culture-confirmed candiduria help in the early detection of candidemia?
      METHODOLOGY: Urine samples were obtained on the day of admission and if negative
      were repeated on the 5th ICU day. Upon laboratory confirmation of candiduria,
      preemptive antifungal therapy was commenced. Whole blood samples were tested
      simultaneously with conventional cultures and PCR repeated twice weekly for two
      weeks. RESULTS: In ICU patients with candiduria, preemptive antifungal therapy
      resulted in candiduria clearance and clinical improvement in 94% of them. Candida
      DNAemia (detected in 64 out of 136 repeated PCR assays) persisted for 1 or 2
      weeks in a significant number of patients. Even after multiple positive PCR
      assays from each individual candiduric patient, the specificity and positive
      predictive value of the assay in the early detection of candidemia were low
      (negative predictive value was 100%). No differences were detected on
      demographics among patients with or without candiduria. The correlations (PCR
      with culture) with kappa test presented a poor agreement (K = 0.103, Kmin= -0679,
      Kmax = 0.103). CONCLUSIONS: PCR in the blood should not be used in early
      diagnosis of (but it could help in excluding) candidemia, in ICU patients with
      candiduria.

PMID- 17523274
TI  - Can procalcitonin help us in timing of re-intervention in septic patients after
      multiple trauma or major surgery?
AB  - BACKGROUND/AIMS: In surgical sepsis, the rapid identification of source of
      infection at an early stage after surgery or serious trauma is crucial for
      favorable outcome. The discrimination between local and generalized infection is
      critical for correct treatment. METHODOLOGY: In a randomized, controlled, single
      centre study we investigated 72 patients with severe sepsis after major abdominal
      surgery or surgery for multiple trauma. Patients were divided in 2 groups: in the
      first group (PCT, n=38), more important role in the treatment decision was given
      to PCT level (severe sepsis with PCT >2 ng/mL signalled bacteremia and pushed us
      to change antibiotics and intravascular devices, severe sepsis with PCT < or =2
      ng/mL prompted use of ultrasonography and/or CT, followed by repeated surgery in
      patients with localized infection). The control group (CON, n=34) was treated by
      standard evaluation of all parameters by consultant surgeon. We investigated 28
      day all-cause mortality, sepsis-related complications, the duration of stay in
      the intensive care unit, and ventilated days. RESULTS: The hospital mortality was
      in PCT group 26% and 38% in control group (p = 0.28). Average SOFA score was 7.9
      +/- 2.8 in PCT group vs. 9.3 +/- 3.3 (p = 0.06). The decline of ICU days (16.1 +/
      6.9 vs. 19.4 +/- 8.9; p = 0.09) and ventilated days (10.3 +/- 7.8 vs. 13.9 +/-
      9.4; p = 0.08) in PCT group was observed, but the difference was not significant.
      CONCLUSIONS: We observed a clear tendency to decrease extent of multiple organ
      dysfunction syndrome in patients, in which therapeutic decision was made earlier
      using procalcitonin as an additional marker separating local infection from
      generalized one.

PMID- 17523275
TI  - Hemodynamic and cardiovascular problems during modified hyperthermic
      intraperitoneal perioperative chemotherapy.
AB  - BACKGROUND/AIMS: Cytoreductive surgery and hyperthermic intraperitoneal
      perioperative chemotherapy (HIPEC) significantly improves patients survival with
      peritoneal carcinomatosis especially in low-grade tumor e.g. ovarian and
      appendiceal adenocarcinoma, peritoneal pseudomyxoma and grade I gastric and
      colorectal cancer. METHODOLOGY: During a period of nine years, hemodynamic and
      cardiac functions combined with urinary output during hyperthermic intraoperative
      intraperitoneal chemotherapy were prospectively measured in 60 patients. RESULTS:
      Statistically significant hemodynamic and cardiac parameters were characterized
      by an increased heart rate and cardiac output as well as decreased systemic
      vascular resistance associated with an increased body temperature and decreased
      effective circulating volume. The tendency of urinary output was to decrease as
      the therapy progressed. CONCLUSIONS: HIPEC induces a hyperdynamic circulatory
      state requiring increased intravenous fluid administration, which avoids changes
      because of increased intra-abdominal pressure. Documented by normal blood
      pressure and adequate urinary output hemodynamic and intravenous fluids, titrated
      to frequent urinary output determination, can achieve cardiac stability.

PMID- 17523276
TI  - Is p53 and heat shock protein 70 expression a useful parameter for preoperative
      hyperthermoradiation therapy in advanced rectal carcinoma.
AB  - BACKGROUND/AIMS: The purposes of preoperative hyperthermoradiation (HR) therapy
      in advanced rectal carcinoma is to decrease the tumor mass and local recurrence
      after the operation and to improve long-term survival. The aim of this study was
      to investigate useful parameters of preoperative HR therapy in advanced rectal
      carcinoma. METHODOLOGY: Thirty-seven patients with primary advanced rectal
      carcinoma located in the lower part of the rectum were treated with preoperative
      HR therapy followed by a curative resection of the rectum. Immunohistochemical
      staining for p53 and heat shock protein (HSP) 70 was performed on biopsied
      specimens obtained from 24 of them. RESULTS: For both p53- and HSP 70-positive
      tumors the effect of HR therapy was good and survival rates were better than with
      for other tumors, but there was no significant correlation between HSP 70
      expression and the effect of HR therapy and survival rates. And there was also no
      significant correlation between p53 expression and the effect of HR therapy and
      survival rates. HR therapy had a significant effect on the G or G4 tumors
      compared with G1 or G2 tumors (p = 0.0277). CONCLUSIONS: Immunohistochemical
      detection of p53 and HSP 70 expressions may be useful for
      hyperthermoradiosensitive patients with advanced rectal carcinoma selected for
      preoperative HR therapy. HR therapy had a significant effect on G3 or G4 tumors
      compared with G1 or G2 tumors.

PMID- 17523277
TI  - A remote educational system in medicine using digital video.
AB  - BACKGROUND/AIMS: Telemedicine has opened the door to a wide range of learning
      experience and simultaneous feedback to doctors and students at various remote
      locations. However, there are limitations such as lack of approved international
      standards of ethics. The aim of our study was to establish a telemedical
      education system through the development of high quality images, using the
      digital transfer system on a high-speed network. METHODOLOGY: Using telemedicine,
      surgical images can be sent not only to domestic areas but also abroad, and
      opinions regarding surgical procedures can be exchanged between the operation
      room and a remote place. The Asia Pacific Information Infrastrucuture (APII)
      link, a submarine cable between Busan and Fukuoka, was used to connect Korea with
      Japan, and Korea Advanced Research Network (KOREN) was used to connect Busan with
      Seoul. Teleconference and video streaming between Hanyang University Hospital in
      Seoul and Kyushu University Hospital in Japan were realized using Digital Video
      Transfer System (DVTS) over Ipv4 network. RESULTS: Four endoscopic surgeries were
      successfully transmitted between Seoul and Kyushu, while concomitant
      teleconferences took place between the two throughout the operations. Enough
      bandwidth of 60 Mbps could be kept for two-line transmissions. The quality of
      transmitted video image had no frame loss with a rate of 30 images per second.
      The sound was also clear, and time delay was less than 0.3 sec. CONCLUSIONS: Our
      experience has demonstrated the feasibility of domestic and international
      telemedicine. We have established an international medical network with high
      quality video transmission over Internet protocol, which is easy to perform,
      reliable, and economical. Our network system may become a promising tool for
      worldwide telemedical communication in the future.

PMID- 17523278
TI  - p53 genetic abnormalities and P-glycoprotein expression in stump and primary
      gastric carcinomas.
AB  - BACKGROUND/AIMS: Genetic abnormalities of the p53 gene may play a major role in
      the carcinogenesis of gastric stump carcinomas (GSC) and intestinal-type primary
      gastric carcinomas (IPGC). Also, they may modulate P-gp expression producing
      chemoresistance. The aim of this article is to analyze p53 genetic abnormalities
      and the influence of p53 gene status on P-gp expression in both types of
      carcinomas. METHODOLOGY: Forty-two paraffin-embedded samples of gastric
      carcinomas corresponding to 17 GSC and 25 IPGC were studied. P53 genetic
      abnormalities in exon 5-9 were screened by direct sequencing of PCR products. P53
      and P-glycoprotein (P-gp) were assessed by a standard streptavidin-biotin
      immunoperoxidase method. Anti-p53 DO7 and anti-P-gp C494 were used as primary
      antibodies. RESULTS: Fourteen p53 mutations were found, 5 in GSC (29%) and 9 in
      IPGC (36%). Thirteen mutations were base-pair substitutions that produced a
      change in the amino acid sequence. Eight mutations were located at exon 7 (57%).
      P53 nuclear immunopositivity was observed in 12 GSC (71%) and 15 IPGC (60%). Only
      two carcinomas (1 IPGC and 1 GSC) harboring a p53 mutation did not show any p53
      expression. All except one of the gastric carcinomas having a p53 mutation showed
      medium or high P-gp expression. However, there was no difference in P-gp
      expression between tumors with and without p53 mutation. CONCLUSIONS: The p53
      genetic alterations found in GSC and IPGC could originate from a similar
      pathogenetic pathway. No association was demonstrated between p53 gene status and
      P-gp expression, although most of the carcinomas harboring a p53 mutation showed
      medium or high P-gp expression.

PMID- 17523279
TI  - Transcatheter arterial chemoembolization with DSM for primary hepatic malignant
      carcinoid.
AB  - A 66-year-old male with multiple liver tumors was diagnosed as having malignant
      carcinoid. The case exhibited carcinoid syndrome with wheezing and high urine 5
      Hydroxy-Indole Acetic Acid and serum serotonin concentrations. A search for the
      primary lesion failed to detect tumors except those in the liver, leading to the
      diagnosis of primary hepatic carcinoid. Repeated transcatheter arterial
      chemoembolization with degradable starch microspheres decreased the tumors in
      size and improved the subjective symptoms. Transcatheter arterial
      chemoembolization with degradable starch microspheres is a useful treatment for
      unresectable malignant carcinoid of liver origin.

PMID- 17523280
TI  - Hepatocellular adenoma with malignant alteration.
AB  - Hepatocellular adenoma is a rare benign tumor of the liver which appears almost
      exclusively in women taking oral contraceptives. Malignant alteration of the
      tumor is very rare with about 12 reported cases. Case outline. We present a 70
      year-old woman who had not taken either oral contraceptive or other hormones ever
      in her life and in whom an abdominal tumor was discovered during the regular
      check-up for arterial hypertension. With ultrasonography and CT scan a solitary
      well demarcated mass within the right liver of otherwise normal appearance was
      diagnosed. During an open surgery a solitary, unilobular, spherical, well
      demarcated tumor on the lower surface of the segments IVb, V and VI of the liver,
      115 x 100 x 90 mm in diameter was excised. The histology revealed a
      hepatocellular adenoma with malignant alteration. The patient is the eldest
      presented case of malignant alteration of hepatocellular adenoma who had never
      taken oral contraceptives or other hormones.

PMID- 17523281
TI  - CT and MRI findings with contrast enhancement of small pancreatic adenocarcinoma
      in the late phase.
AB  - A 60-year-old female was found to have high serum amylase concentrations at a
      medical check-up. Dynamic computed tomography and magnetic resonance imaging
      demonstrated a mass in the body of the pancreas, which was enhanced in the late
      phase of the scans by administration of a contrast medium. Endoscopic retrograde
      pancreatography showed a stenosis of the main pancreatic duct at the body, and
      brushing cytology from the region revealed adenocarcinoma. Distal pancreatectomy
      was performed. The tumor was a well-differentiated adenocarcinoma, measuring 15 x
      l0 mm. Fibrous tissues were sparsely distributed in the tumor, and there was an
      increase of dilated veins, in particular at the margin. Late-phase enhancement of
      the tumor with computed tomography or magnetic resonance imaging was considered
      to be correlated with this abundant vascular structure in the tumor. Marked tumor
      enhancement in the late phase might be a characteristic finding suggesting an
      early-stage pancreatic adenocarcinoma, which should be carefully checked.

PMID- 17523282
TI  - A case report of a 39-year-old male with choledochal cyst mimicking pancreatic
      pseudocyst.
AB  - In European countries, choledochal cysts are rare anomalies of the bile tract. At
      the Surgery Department of the University Hospital Ostrava, a case of a patient
      with cystic lesion of the pancreatic head was solved. According to
      ultrasonography and computer tomography it was assumed to be a pancreatic
      pseudocyst. Only after a complete additional examination of the pancreatico
      biliary system, was it diagnosed Ia-type cystic dilatation of the common bile
      duct, accompanied by stenosis in its terminal part. With regard to the age of the
      first clinical symptoms, their character and histopathological findings,
      congenital origin is assumed in both of these anomalies. After provisional
      percutaneous transhepatic biliary drainage, a duodenohemipancreatectomy was
      performed with complete cyst excision. Until now, nine months later, the patient
      has shown absolutely no clinical difficulties.

PMID- 17523283
TI  - Imaging modality of three-dimensional CT in caudate cholangioma: assessment for
      resectability.
AB  - Conventional preoperative imaging has limited modality and accuracy in primary
      intrahepatic cholangiocellular carcinoma (ICC) in the caudate lobe (CL).
      Furthermore, estimating resectability and tumor extension from preoperative
      imaging is inaccurate. A 60-year-old patient with ICC administrated in our
      institution requested a second opinion. His lesion was judged unresectable hilar
      cholangiocellular carcinoma because it had spread widely to the bilateral lobe of
      the liver as shown by preoperative imaging studies. The irregular shaped mass was
      located in the para-caval portion of the CL and the size as shown by computed
      tomography (CT) was 40mm in diameter. The tumor extended close to the common
      hepatic artery and the right portal branch was involved. The left lobe showed
      marked atrophy and intrahepatic biliary duct (IHBD) dilatation of the whole liver
      was observed. The tumor was mainly located in the proximal side of the left lobe
      and every IHBD were interrupted in the porta hepatis by magnetic resonance
      cholangiopancreatography and endoscopic retrograde cholangiography. However, the
      resectability of this tumor could not be determined from these imaging studies.
      Three-dimensional imaging by multidetector CT (3D-CT) revealed that the tumor
      involved the left hepatic artery and portal branch whereas the right hepatic
      artery was intact. The patient was successfully treated in surgery by extending
      the left lobectomy with en bloc caudate lobectomy. The 3D-CT imaging study was
      helpful in assessing the resectability in ICC of CL.

PMID- 17523284
TI  - The influence of type of operation for distal rectal cancer: survival, outcomes,
      and recurrence.
AB  - BACKGROUND/AIMS: This study analyzed the results of treatment of rectal cancer
      (tumor within 12 cm of the anal verge) with different techniques. METHODOLOGY:
      Two hundred and sixty-four patients who had undergone elective curative surgical
      resection of rectal cancer within 12cm of the anal verge were evaluated. The
      operative data and follow-up data were collected prospectively. Comparisons were
      made between patients who had different surgical procedures. RESULTS: The overall
      peroperative mortality rate was nil, and the morbidity 39.4%. Local recurrence
      occurred in 21 of the patients with a median follow-up of 34 months (range: 5-105
      months). The 3-year actuarial local recurrence rates for double-stapled
      anastomosis, low straight anastomosis and APR were 25%, 6%, and 5%, respectively.
      The local recurrence rate was significantly higher for double-stapled low
      anterior resection than for the other types of operation (p = 0.013). On
      multivariate analysis reconstruction with Knight-Griffen anastomosis (p = 0.013)
      and tumor distance from the anal verge <6 cm (p = 0.001), were associated with
      local recurrence but only stage was a significant prognosticator of overall
      survival (p = 0.012). CONCLUSIONS: Following total mesorectal excision, the local
      recurrence rate was higher in patients treated with double-stapled low anterior
      resection than in those with termino-terminal low anterior resection or APR;
      survival rates were similar in these groups.

PMID- 17523285
TI  - Long-term functional changes after low anterior resection for rectal cancer
      compared between a colonic J-pouch and a straight anastomosis.
AB  - BACKGROUND/AIMS: We prospectively compared changes in function between colonic J
      pouch and straight anastomoses from 1 to 5 years after low anterior resection for
      rectal cancer. METHODOLOGY: At 1, 3, and 5 years after surgery, functional
      outcome was compared between 48 patients with J-pouch reconstruction (J group)
      and 51 with straight anastomosis (S group), using a 17-item questionnaire
      (overall best, 0; overall worst, 26). Reservoir function was evaluated
      manovolumetrically. RESULTS: At 5 years, patients with ultralow anastomoses (< or
      =4 cm from anal verge) had fewer bowel movements during day or night, and less
      urgency and soiling in the J than S group. At that time, patients with low
      anastomoses (5 to 8 cm above the verge), had fewer bowel movements at night and
      less urgency in the J than S group. Manovolumetric results were better in the J
      than S group for both anastomotic levels. Functional scores improved
      significantly over time for both anastomotic levels, especially in the S group.
      Mean scores with ultralow anastomoses were J-group, 5.6 at 1 year vs. 5.3 at 3
      years (P = 0.0304) vs. 3.7 at 5 years (P < 0.0001); and S group, 10.2 at 1 year
      vs. 9.6 at 3 years (P = 0.0063) vs. 7.3 at 5 years (P < 0.0001). Mean scores with
      low anastomoses were J group, 3.4 at 1 year vs. 3.1 at 3 years (P = 0.0052) vs.
      2.1 at 5 years (P = 0.0003); and S group, 5.2 at 1 year vs. 3.8 at 3 years (P <
      0.0001) vs. 2.7 at 5 years (P < 0.0001). Manovolumetric results improved overtime
      in both groups. CONCLUSIONS: Functional outcome improved in the J and especially
      the S group over 5 years. However, function was better in the J than S group at
      all time points.

PMID- 17523286
TI  - Triangulating stapling technique for reconstruction after colectomy.
AB  - BACKGROUND/AIMS: To retrospectively compare the triangulating stapling technique
      for colocolonic anastomosis with hand-sewn anastomosis and functional end-to-end
      anastomosis. METHODOLOGY: Data from 646 patients who underwent colectomy for
      cancer from 1993 to 2004 were extracted by chart review. Patients were divided
      into three groups based on the type of anastomosis: handsewn (n=233), functional
      end-to-end (n=71), and the triangulating stapling method (n=346). Demographic
      data and clinical characteristics of the three groups were similar. RESULTS:
      Anastomotic leakage was significantly more common in the hand-sewn group than the
      triangular stapling group (hand-sewn; 3.0%, functional end-to-end; 2.8%,
      triangulating, 0.6%) (P < 0.05). No patient developed bleeding or stenosis at the
      anastomosis, and the incidence of wound infection was equivalent among the three
      groups. One death due to anastomotic failure occurred in each of the functional
      end-to-end and triangulating stapling groups. The cost of triangulating stapling
      was approximately Yen 36,000 lower than the cost of the functional end-to-end
      anastomosis. CONCLUSIONS: The triangulating stapling technique is an attractive
      alternative to other methods for creating a colocolonic anastomosis.

PMID- 17523287
TI  - Clinical significance of small colorectal adenoma less than 10 mm: the KASID
      study.
AB  - BACKGROUND/AIMS: Polypectomy is the current modality of choice to prevent benign
      colorectal adenoma from progressing to an invasive cancer. However, in cases of
      small colorectal adenoma, it remains unclear as to whether polypectomy is
      actually an effective treatment modality. We evaluated the clinical significance
      of polypectomy in cases of small colorectal adenomas, measuring less than 10 mm.
      METHODOLOGY: All colonoscopies were performed at 11 Korean tertiary medical
      centers, between July 2003 and March 2004. A total of 5996 colorectal adenomas
      were detected and divided into 5 groups according to their size (Group 1; 1-5 mm,
      Group 2; 6-7 mm, Group 3; 8-9 mm, Group 4; 10-19 mm, Group 5; more than 20 mm).
      The term 'advanced adenoma' refers here to tubular adenomas with diameters of at
      least 10 mm, or to tubulovillous, villous, or high-grade dysplasia, irrespective
      of size. 'Cancer' here is defined as the invasion of malignant cells beyond the
      muscularis mucosa. RESULTS: As the sizes of the adenomas increased, the
      prevalence of advanced adenoma was also observed to increase. In Groups 2 and 3,
      the prevalence of tubulovillous or villous adenoma were higher than was expected
      (5.2% and 6.6%, p < 0.001). Interestingly enough, in Group 2, the prevalence of
      cancer was at least as high as in Group 4 (0.7% vs. 0.5%, p < 0.001).
      CONCLUSIONS: In cases of small colorectal adenomas, measuring between 6 and 9 mm,
      the prevalence of cancer was at least as high as that seen in the cases of
      colorectal adenomas measuring between 10 and 19 mm. Therefore, small colorectal
      adenomas measuring between 6 and 9 mm should not be ignored, in order to decrease
      the prevalence of colorectal cancer.

PMID- 17523288
TI  - Segmental resection, lymph nodes dissection and survival in patients with left
      colon cancer.
AB  - BACKGROUND/AIMS: To evaluate retrospectively in patients who have undergone
      elective surgery for left colon cancer, if extent of segmental resection may
      affect postoperative outcome, lymph nodes dissection and long-term survival.
      METHODOLOGY: With lesion localized at the sigma or descending colon, 129 patients
      were divided into two groups according to the length of operative specimens:
      group 1: 73 cases, length 8 to < or =25 cm, who were surgically treated with
      limited segmental resection; group 2: 56 cases, length >25 to >50 cm, who had
      undergone extensive segmental resection. In no patient was ligation at the root
      of the inferior mesenteric artery performed. Lymph node dissection of pericolic
      nodes (N1) and occasionally intermediate nodes (N2) in group 1 and electively of
      N1 and N2 nodes in group 2 was carried out. RESULTS: Median follow-up was 60 and
      56 months for group 1 and 2, respectively. In group 1 a median of 8 lymph nodes
      were removed compared to a median of 13 nodes retrieved in group 2, where a
      significant prevalence of N2 nodes was found compared to group 1 (p = 0.024). The
      incidence of N+ cases according to the total number of nodes removed is
      superimposable in the two groups. Overall disease-free survival was better, but
      not significantly, in group 1 compared to group 2; whereas actuarial survival
      curves of Dukes C cases, according to two types of resection, were similar.
      CONCLUSIONS: This retrospective study shows that in patients with left colon
      cancer long-term survival does not seem to be significantly affected by the
      extent of segmental resection.

PMID- 17523289
TI  - Colorectal cancer among patients aged 75 years or over.
AB  - BACKGROUND/AIMS: The aim of this study is to evaluate the risk factors for
      mortality, morbidity, and long-term survival in elderly patients with colorectal
      cancer when compared to younger patients. METHODOLOGY: Patients operated on with
      colorectal cancer were divided into 2 groups according to age: Group 1 (75 years
      old or older, n=90) and group 2 (<75 years, n=430). RESULTS: Preoperative
      hemoglobin levels were lower in group 1 (p = 0.008). Poorer clinical status
      defined by ASA score (p = 0.008) results and blood transfusions (p = 0.003) were
      more frequent in group 1 when compared to group 2. Group 1 had a significantly
      higher operative mortality rate than group 2 (p = 0.01). Regarding cancer-related
      survival after 1, 2, and 4 years, there was no significant difference between the
      2 groups. CONCLUSIONS: Poorer clinical conditions with special regard to anemia
      are more frequent among patients of 75 years and older and this finding may lead
      to an increase in operative mortality when compared to younger patients. Even
      though, senior patients with colorectal cancer should not be denied surgical and
      adjuvant therapy on account of age alone since cancer-related survival remains
      comparable to younger patients' results.

PMID- 17523290
TI  - Successful management of latrogenic aortoduodenal fistula by intraaortic
      endovascular stent-graft and duodenal diversion.
AB  - Aortoduodenal fistula is usually fatal if not treated promptly. Long-term results
      are also not always satisfactory. A 53-year-old female patient suffered from
      massive hematemesis and shock due to an iatrogenic aortoduodenal fistula which
      was made during a laparoscopic total colectomy. Immediate closure of fistula with
      duodenal diversion by occlusion of duodenal lumen proximal to the fistula,
      bilateral truncal vagotomy and pyloroduodenojejunostomy were performed.
      Endoluminal aortic stent graft was inserted 3 days later. The patient remained
      disease-free 3 years after operation. With a prompt diagnosis, duodenal diversion
      with endoluminal aortic stent may be a better option for iatrogenic aortoduodenal
      fistula.

PMID- 17523291
TI  - Does an acute increase of intraabdominal pressure effect esophageal sphincter
      pressure?
AB  - BACKGROUND/AIMS: The study was designed to observe the acute alterations between
      lower esophageal sphincter (LES) and intraabdominal pressure (IAP) in patients
      undergoing diagnostic laparoscopy. METHODOLOGY: Eleven patients (7 Male), aged 49
      fitting the criteria for manometric research and diagnostic laparoscopy were
      studied. To measure the IAP in sterile conditions a new device (IAP measurement
      system) was set. Pressures at basal (b), during intraabdominal CO2 insufflations
      (min, m2, m3) and at the end of laparoscopy (me), were recorded simultaneously.
      All results were given as the difference between two maneuvers (A). Paired sample
      t-test was used. RESULTS: The results were as follows; at the time of maximum CO2
      insufflations: p delta m1-b; 24.25 vs. 14.64 mmHg, during the stabile
      insufflations: p delta m2-m1; -2.88 vs. 2.99 mmHg, p delta m3-m2; -0.70 vs. -0.82
      mmHg and after deflation of CO2; end of the laparoscopy; p delta m(e)-m3; -16.73
      vs. -16.65 mmHg for LESP and IAP respectively. The response of the LESP and IAP
      were similar in all phases (p > 0.05). Also alterations of pressures according to
      gender or presence of cirrhosis were found to be similar. CONCLUSIONS: LESP is
      changed synchronously in the presence of acute pressure changes in IAP. Gender or
      presence of cirrhosis does not affect the response of LES.

PMID- 17523292
TI  - The relationship between MIB-1 proliferative activity and mitotic index in
      gastrointestinal stromal tumors.
AB  - BACKGROUND/AIMS: Gastrointestinal stromal tumors (GIST) are mesenchymal tumors
      originating from the gastrointestinal canal wall. Although a number of studies
      are performed concerning prognostic factors, no indicators of recurrence or
      metastasis could be established. In this study we assessed the prognostic value
      of MIB-1 proliferative index (PI) in GIST, and whether there was a relationship
      to any other clinicopathological findings. METHODOLOGY: In the study 37 patients
      with GIST diagnosis were included. The cases were classified as low,
      intermediate, and high risk groups according to tumor size and mitotic activity.
      The average PI of 10% in high risk group was set as the cut-off value. RESULTS:
      Of all the cases, those with a MIB-1 PI over the cut-off value had a
      significantly shorter survival (Log-rank test, p < 0.05). Likewise cases with
      small bowel tumors with a MIB-1 PI over the cut-off value had a significantly
      shorter survival (Log-rank test, p < 0.05). A statistically significant negative
      correlation was found between presence of necrosis and survival using McPearson
      correlation test (p < 0.01). CONCLUSIONS: MIB-1 PI and presence of necrosis are
      possible indicators of prognosis especially in GIST cases of the small bowel.

PMID- 17523293
TI  - Difference in accuracy between gastroscopy and colonoscopy for detection of
      cancer.
AB  - BACKGROUND/AIMS: There are few reports regarding the accuracy of endoscopy in
      detecting cancer. We investigated the difference in the false-negative rates for
      cancer detection between gastroscopy and colonoscopy using the records of a
      population-based cancer registry, which is the most accurate in Japan.
      METHODOLOGY: Between 1990 and 1995, 51,411 gastroscopic and 7756 colonoscopic
      examinations were carried out in our hospital. These subjects were matched with
      the cancer registry and the patients whose gastric or colorectal cancers were
      missed by examinations were identified. RESULTS: The false-negative rate for the
      detection with gastroscopy was 25.8 percent at three years but that with
      colonoscopy was 11.1 percent. This difference was statically significant p =
      0.01. CONCLUSIONS: We concluded that for routine examinations, surveillance after
      negative endoscopy should be discussed based on the difference in false-negative
      rates between gastroscopy and colonoscopy.

PMID- 17523294
TI  - Post-prandial portal hemodynamics after upper gastrointestinal tract abscission.
AB  - BACKGROUND/AIMS: The purpose of this study is to analyze the changes in post
      prandial portal hemodynamics after upper gastrointestinal tract abscission, using
      pulsed Doppler ultrasonography. METHODOLOGY: The study group consisted of normal
      volunteers and patients who had undergone total gastrectomy (TG), distal partial
      gastrectomy (PG), transthoracic esophagectomy and reconstruction with a gastric
      tube (TE), pancreatoduodenectomy (PD), or pylorus-preserving
      pancreatoduodenectomy (PPPD). The maximal portal blood flow velocity (Vmax) was
      measured by the pulsed Doppler method before and after nutrient intake. Ratio of
      each postprandial mean Vmax to pre-prandial mean Vmax was described as ratio of
      flow velocity (RFV). RESULTS: In the TG group, the RFV curve shifted markedly to
      the left in comparison to that in the control and PG groups. The pattern in the
      TE group was similar to that in the control group. In the PD group, the curve
      shifted to the left in comparison to that in the control group. In the PPPD
      group, the RFV was low throughout the examination. The pattern in the PPPD
      Billroth-I reconstruction group was similar to that in the control group, but not
      to the PPPD Billroth-II reconstruction group. CONCLUSIONS: The pattern of RFV
      reflectedfood transport dynamics after upper gastrointestinal surgery.

PMID- 17523295
TI  - Streptococcus pneumonia endocarditis associated with gastrointestinal malignancy.
AB  - Particular systemic infections have been found to be associated with concurrent
      malignancies sufficiently commonly as to warrant search for malignancy in
      patients with such infections. The current study adds Streptococcus pneumonia
      endocarditis to the list of relevant infections.

PMID- 17523296
TI  - A case of laparoscopic surgery for blue rubber bleb nevus syndrome.
AB  - A 33-year-old woman had presented with some cutaneous and gastrointestinal
      hemangiomas with iron deficiency anemia three years previously and blue rubber
      bleb nevus syndrome was diagnosed. Although she had taken an iron supplement for
      three years, she hoped to discontinue it and underwent laparoscopic surgery for
      nine gastrointestinal hemangiomas. She was discharged on the ninth postoperative
      day without any complications. She has been fit without iron deficiency anemia
      for a year since the operation. Blue rubber bleb nevus syndrome is a rare disease
      accompanied with cutaneous and gastrointestinal vascular malformations and about
      150 cases have been reported. To the best of our knowledge, this is the first
      report of blue rubber bleb nevus syndrome with small and large intestinal lesions
      that were treated with laparoscopic surgery.

PMID- 17523297
TI  - Comments on Rome criteria of functional gastrointestinal disorders.
AB  - The following comments and critical remarks on Rome criteria are submitted on the
      basis of 50 years' experience: Rome criteria do not distinguish between non
      organic disturbances which are truly digestive and those which are neuropathic or
      psychopathic. Yet the distinction is important both theoretically and
      practically. Dyspepsia is defined as pain or discomfort in the epigastrium but
      distinction of both terms is important for identification of subgroups and for
      therapy. An alternative and useful basis for definitions of functional digestive
      disorders is the sensations accompanying eating and defecation. Rome criteria
      disregard the fact that the distinction of functional from organic is not in the
      symptoms themselves but rather in the circumstances in which they appear or
      disappear. In Rome criteria some conditions are incorrectly interpreted (globus,
      aerophagia) and some typical syndromes are not mentioned namely fermentative
      enteropathy (carbohydrate dyspepsia) and pain arising in the abdominal nervous
      plexus - solar (celiac plexus) syndrome.

PMID- 17523298
TI  - Perioperative morbidity in hepatic surgery.
AB  - BACKGROUND/AIMS: The aim of this study was to identify potentially prognostic
      factors that could predict the morbidity and mortality of liver resection for
      metastatic cancer. METHODOLOGY: From January 1990 through December 1999, 136
      patients who were treated for liver metastases of all primaries were identified
      from a prospective database. A stepwise procedure using logistic regression
      analysis was used to identify prognostic factors. RESULTS: Postoperative
      morbidity and mortality were 27% (95% confidence interval: 20-36%) and 2% (95%
      confidence interval: 0.0-4.0%) respectively. In our series we found the duration
      of surgery (postoperative complications increasing from 10% for operations of 2
      hours or less to 44% for operations of more than 3.5 hours) and perioperative
      blood transfusion as prognostic factors for postoperative complications in
      general; we found a specific relation between extended right hemihepatectomy and
      postoperative bile duct related problems. CONCLUSIONS: Elective hepatic surgery
      is safe, irrespective of its extent. The importance of technical measures to
      prevent blood loss and bile leakage has to be underlined. No perioperative factor
      could be determined to be exclusionary when considering a patient for resection.

PMID- 17523299
TI  - Lack of susceptibility to ischemic necrosis of the remnant liver following
      partial hepatectomy in the rat.
AB  - BACKGROUND/AIMS: The increase in liver lobule dimensions that occurs following
      partial hepatectomy could predispose living related donors to ischemic hepatic
      injury were shock-like states to occur in the future. METHODOLOGY: In the present
      study, rats that had undergone 70% partial hepatectomies or sham surgery six
      weeks earlier were progressively bled to a maximum of 40% total circulating blood
      volume. RESULTS: Despite significant increases in liver lobule dimensions (1.5x
      controls), hepatectomized rats did not manifest biochemical or histologic
      evidence of early or more extensive hepatic injury when compared to sham-operated
      controls. CONCLUSIONS: The results of this study suggest that despite theoretical
      concerns, living related donors are not predisposed to develop ischemic hepatic
      injury were shock-like states to develop in the future.

PMID- 17523300
TI  - Soluble P selectin levels in chronic liver disease: relationship to disease
      severity.
AB  - BACKGROUND/AIMS: Thrombocytopenia and platelet function abnormalities are
      problems commonly found in patients with chronic liver disease (CLD). Despite
      lack of widespread recognition as to the clinical significance of Soluble P
      selectin (sP-selectin), in that increased levels of sP-selectin have been
      described in patients with CLD, it has been proposed as a marker of in-vivo
      platelet activation. The study's aim was to determine whether levels of sP
      selectin in patients with CLD increase in accordance with the degree of liver
      failure, the likelihood of CLD patients with high sP-selectin levels being more
      prone to thrombosis, as well as investigating the coagulation and fibrinolytic
      parameters related to the sP-selectin. METHODOLOGY: This study was comprised of
      two groups: 40 patients with cirrhosis and portal hypertension (28 males and 12
      females); and a control group of 10 healthy volunteers (6 males and 4 females).
      In both groups, biochemical parameters, sP-selectin, coagulation and fibrinolytic
      activity levels were measured and a Doppler ultrasound was performed. RESULTS:
      Plasma sP-selectin levels were found to be higher in the patients compared to
      those of the control group (p < 0.01), while at the same time significant
      differences were observed with respect to the stage of disease. Patients with low
      platelet counts were found to have higher sP-selectin levels than those with
      normal platelet counts (p < 0.01). Seven patients (17.5%) were seen to have
      portal vein thrombosis upon doppler ultrasound examination, while sP-selectin
      levels were significantly lower in those patients with thrombosis than those
      without (p < 0.05). It was our finding that sP-selectin levels inversely
      correlated with anti thrombin III. CONCLUSIONS: In conclusion, sP-selectin levels
      related to the degree of liver disease and thrombosis are seen together with low
      platelet and sP-selectin levels in patients with cirrhosis.

PMID- 17523301
TI  - Evaluation of tube drainage method in the treatment of hydatid cyst of liver.
AB  - BACKGROUND/AIMS: It has been reported that surgical methods such as
      marsupialization and tube drainage were unfavorable due to their possible
      complications in surgical treatment of hydatid cyst in liver. We aimed to compare
      tube drainage technique with other surgical modalities. METHODOLOGY: Seventy-two
      patients who underwent surgical treatment due to hydatid cyst of liver in Haseki
      Education and Research Hospital between 2000 and 2003 constituted our study
      group. The mean age of patients was 42 +/- 17 years, 31 being male and 41 being
      female. Tube drainage was applied to 32 patients, whereas the remaining 40
      patients were treated by other surgical methods such as omentoplasty, total
      cystectomy, intraflexion, capitonnage. These two groups of patients were compared
      with each other according to their postoperative hospitalization time and
      resulting complications. RESULTS: The complication rate was 28.1% in patients who
      underwent tube drainage. Their mean postoperative hospitalization time was 7.3 +/
      3.19 days. The complication rate was 17.5% in patients who underwent any kind of
      surgery other than tube drainage. Their mean postoperative hospitalization time
      was 7.4 +/- 4.5 days. No statistical significant difference was found in the
      comparison of these two groups concerning both the postoperative hospitalization
      time and the rate of complications (p > 0.05). CONCLUSIONS: The method of tube
      drainage is a safe surgical modality in the treatment of hydatid cyst disease of
      liver if applied properly on appropriate patient according to the data we
      obtained.

PMID- 17523302
TI  - Long-term follow-up of hepatic hemangiomas by ultrasonography: with emphasis on
      the growth rate of the tumor.
AB  - BACKGROUND/AIMS: It is not rare to find hepatic hemangiomas in people in Taiwan
      where hepatitis B is endemic during ultrasonographic examinations for the
      screening of hepatocellular carcinoma, and we can therefore monitor these
      hemangiomas longitudinally since detected. METHODOLOGY: Totally 180 hepatic
      hemangiomas in 130 adult patients were followed up for more than 5 years with at
      least twice ultrasound examinations in our hospital. The diagnosis of hemangiomas
      was made by typical ultrasonographic findings as well as compatible findings in
      other imaging modalities. The largest diameter of the same tumor at various
      examinations was compared in each patient. The doubling time of tumor volume was
      calculated for the enlarging hepatic hemangiomas. RESULTS: The diameters of the
      180 hemangiomas ranged from <8 cm - >4 cm in 11 (6.1%), < or =4 cm - >2 cm in 55
      (30.6%), and < or =2 cm in 114 (63.3%). Among them, the diameter of 14 (7.7%)
      hemangiomas in 13 patients increased. The tumor volume doubling time of these
      hemangiomas ranged from 17.3 to 178.1 months. CONCLUSIONS: Although hepatic
      hemangiomas are benign, some of them indeed grow slowly. The growth rates of
      these hemangiomas varied and were definitely slower as compared with those of
      malignant hepatic tumors.

PMID- 17523303
TI  - Hepatic encephalopathy due to TIPS--retrospective study.
AB  - BACKGROUND/AIMS: The main problem of transjugular intrahepatic portosystemic
      shunt is high incidence of hepatic encephalopathy (HE). The aim of our
      retrospective study was to determine the incidence the risk factors of clinically
      significant encephalopathy. METHODOLOGY: 430 patients with liver cirrhosis
      treated by TIPS in Faculty Hospital in Hradec Kralove, Czech Republic. RESULTS:
      Incidence of HE was 35.8%. Patients with HE were older (57.7 +/- 12.1 years) than
      patients without HE (50 +/- 1.4 years) (p < 0.001). HE developed in 28.6% in
      patients with ethylic etiology and in 43.9% in patients with non-ethylic etiology
      (p < 0.001). In diabetic patients HE developed in 51.6% (47 of 111), as compared
      with 30.5% (44 of 319) in non-diabetic patients (p < 0.01). We did not observe a
      difference in the incidence of HE in relation to sex, stage of cirrhosis,
      diameter of the stent nor the drop of the portosystemic gradient. Multivariance
      analysis revealed however to be statistically significantly conditioned by age
      and not by the presence of diabetes or etiology of liver cirrhosis. CONCLUSIONS:
      The risk factors for HE in our patients were older age, other than ethylic
      etiology of liver cirrhosis and diabetes mellitus. There was no direct
      relationship between the development of HE and other investigated parameters.

PMID- 17523304
TI  - Efficacy of color sonography and harmonic scalpel in laparoscopic management of
      multiple/lobulated liver cysts and abscesses.
AB  - BACKGROUND/AIMS: Major concerns of multiple/lobulated liver cysts and abscesses
      managed by laparoscopic approach are inadequate deroofing/ drainage and
      hemorrhage. The aim of this study was to test the efficacy of color sonography
      and ultrasonically activated scalpel employed in this field. METHODOLOGY: Ten
      patients with multiple/lobulated liver cysts and eight patients with lobulated
      pyogenic liver abscesses were managed laparoscopically with the aid of
      laparoscopic color sonography and harmonic scalpel. Clinicopathological data,
      operative results, complications, and follow-up were retrospectively analyzed.
      RESULTS: Ten patients with liver cysts underwent laparoscopic deroofing, in
      addition to hepatectomy (n=3), cholecystectomy and adrenalectomy (n=l), and
      Nissen fundoplication (n=1). The number of multiple/lobulated liver cysts
      deroofed was 5.8 +/- 3.3 (range, 4 to 12). There was no mortality and morbidity
      in these 10 patients. Eight patients with multilobulated liver abscess underwent
      laparoscopic drainage, in addition to cholecystectomy (n=3), without conversion.
      There was no need of blood transfusion perioperatively. The major complications
      of eight liver abscess cases included residual abscess and prolonged ventilator
      in one each. Followed-up with a mean time period of 26 +/- 8 months, all patients
      except one were well without symptomatic recurrence. CONCLUSIONS: Color
      sonography and harmonic scalpel made laparoscopic management of
      multiple/lobulated liver cysts and abscesses more efficacious in terms of precise
      localization, adequate deroofing/drainage, and better hemostasis.

PMID- 17523305
TI  - Gene expressions associated with chemosensitivity in human hepatoma cells.
AB  - BACKGROUND/AIMS: Only limited patients with hepatoma benefit from chemotherapy
      without a clear explanation. We aimed to identify genes associated with
      chemosensitivity using transcriptional profiles. METHODOLOGY: In 8 hepatoma cells
      (HLE, HLF, Huh7, Hep3B, PLC/PRF/5, SK-Hep1, Huh6, and HepG2) transcriptional
      profiles were obtained using cDNA microarray including 2300 genes.
      Chemosensitivities to 8 anticancer drugs (nimustine, mitomycin C, cisplatin,
      carboplatin, doxorubicin, epirubicin, mitoxantrone, and 5-fluorouracil) were
      measured by obtaining 50% growth inhibitory concentrations (GI50) using MTT
      assay. Genes having drug-specific association with chemosensitivity were
      selected. RESULTS: Up-regulation of topoisomerase II beta was associated with
      chemo-resistance, the target of doxorubicin. Platinum-specific resistance was
      associated with superoxide dismutase 2 expression. Antigen peptide transporter 1
      expression correlated with nimustine and mitoxantrone-specific susceptibility.
      These results were verified by semi-quantitative RT-PCR. Drug inactivators
      reported in non-liver cancers such as multidrug transporters and drug
      metabolizers showed less diversity of chemosensitivity in hepatoma cells.
      CONCLUSIONS: To evaluate these gene expressions may be useful to select
      anticancer drugs, and possibly to consider new therapeutic target to modify drug
      action.

PMID- 17523306
TI  - Serum immunoglobulins in patients with chronic hepatitis C: a surrogate marker of
      disease severity and treatment outcome.
AB  - BACKGROUND/AIMS: Moderate polyclonal hypergammaglobulinemia is a common finding
      in chronic viral liver disease; however, its clinical significance has not been
      completely elucidated. We attempted to determine whether serum immunoglobulin
      levels were correlated with the disease severity and the treatment outcome in
      patients with chronic hepatitis C. METHODOLOGY: In a total of 102 patients with
      chronic hepatitis C, we performed serum tests on immunoglobulins and determined
      the histology activity index (HAI) score by liver biopsy. In 97 patients,
      immunoglobulin levels were followed prior to and 6 months after interferon (IFN)
      therapy. RESULTS: Serum gamma (y)-globulin and immunoglobulin (IgG) were well
      correlated with HAI score (both; p < 0.0001), grading score (both; p < 0.01), and
      staging score (both; p < 0.0001). Among the 97 patients who received 6 months of
      IFN monotherapy, 31, 29, and 37 patients were complete, transient and non
      responders, respectively. In the three subgroups, a significant difference was
      found in histological HAI, grading, and staging scores (p < 0.01, p < 0.05 and p
      < 0.0001, respectively), and in serum levels of gamma-globulin and IgG (both; p <
      0.0001). Following IFN treatment, serum gamma-globulin and IgG were significantly
      decreased in the complete responders (both; p < 0.0001). Furthermore, serum
      levels of gamma-globulin and IgG of 1.5 g/dL were useful for predicting the
      treatment outcome of IFN monotherapy. CONCLUSIONS: The measurement of serum gamma
      globulin and IgG is a valuable non-invasive tool for assessing the disease
      severity and treatment outcome in patients with chronic hepatitis C.

PMID- 17523307
TI  - Tumor thrombus types influence the prognosis of hepatocellular carcinoma with the
      tumor thrombi in the portal vein.
AB  - BACKGROUND/AIMS: To evaluate the benefits of the tumor thrombus types system on
      determining treatments and prognosis of hepatocellular carcinoma patients (HCC)
      with tumor thrombi in the portal vein. METHODOLOGY: According to anatomic
      features of the portal vein in the liver and tumor thrombus of HCC developing
      modes, a uniform tumor thrombus types system (types I-IV) was first recommended.
      84 HCC patients with portal vein tumor thrombi, which from January 2000 to
      January 2003 in the Eastern Hepatobiliary Surgery Hospital, were divided into I
      IV groups according to types I-IV of the tumor thrombus system. The median
      survival periods and effectiveness of surgical resection or non-resection for I
      IV groups were retrospectively observed. RESULTS: The median survival periods for
      patients of group I (n=17), II (n=26), III (n=35) and group IV (n=6) were 10.1,
      7.2, 5.7 and 3.0 months, respectively (p = 0.0001). From tumor thrombus type I to
      type III, the patients received surgical resection were better than that of non
      resection (P = 0.0006). Among the patients receiving resection treatment,
      resection of tumor thrombus type I had the best effects, while for patients with
      tumor thrombus type IV, the results were not good. In case of non-resection
      treatments, the survival periods of patients with tumor thrombi type I, II and
      III were similar, which supposed that TACE may be of little effects on tumor
      thrombi. CONCLUSIONS: Types of tumor thrombus system suggested may be helpful to
      determine the treatments and prognosis of HCC patients with tumor thrombi in the
      portal vein.

PMID- 17523308
TI  - Laparoscopic biliary bypass--a single centre experience.
AB  - BACKGROUND/AIMS: To review the results of laparoscopic biliary bypass for both
      benign and malignant pathologies in a minimal access surgery training center.
      METHODOLOGY: Retrospective review of a prospectively maintained database of
      laparoscopic biliary bypass during the period 1995-2004. RESULTS: During the
      review period 1995-2004, there were 26 laparoscopic biliary bypasses performed in
      our center which included 23 laparoscopic choledochoduodenostomy (LCD), 2
      laparoscopic roux-en-Y choledochojejunostomy (LCJ) and 1 laparoscopic
      cholecystojejunostomy (LCCJ). Of the 23 LCD, all except 1 patient were operated
      for recurrent pyogenic cholangitis (RPC). The 2 LCJ and 1 LCCJ were performed for
      patients with advanced carcinoma in the periampullary region and simultaneous
      laparoscopic gastrojejunostomy (LGJ) was also performed to relieve the gastric
      outflow obstruction. Among the 23 LCD, there were 2 open conversions (7.7%) for
      lost broken tip of ultrasonic dissector and significant bleeding during
      choledochotomy respectively. Major complications occurred in 6 patients (23%),
      which included 3 bile leaks (11.5%), 1 intraabdominal collection (3.8%). 1 wound
      infection (3.8%) and 1 gastric stasis (3.8%). The only mortality in our series
      was a patient with carcinoma of head of pancreas undergoing simultaneous roux-en
      Y LCCJ and LGJ. He had persistent gastric stasis after operation and required
      revision surgery for the kinked cholecystojejunostomy anastomosis. He finally
      died of myocardial ischemia after the second operation. As for the postoperative
      pain control, the mean pethidine consumption was 243.4 +/- 254.7 mg (range 0-1200
      mg) and mean dologesic usage was 16.2 +/- 20.4 tablets (range 0-94 tablets). The
      average postoperative hospital stay was 12.6 +/- 11.5 days (range 5-60 days). The
      long-term functional results were satisfactory and only 1 patient had recurrent
      stone upon a mean follow-up of 32.3 months. Among the patients with malignant
      biliary obstruction, the only mishap was as previously mentioned and the
      remaining 2 patients could enjoy satisfactory palliation for more than a year
      before death. CONCLUSIONS: Laparoscopic bypass is not only feasible but also
      highly effective in relieving biliary obstruction with good postoperative results
      in both benign and malignant conditions.

PMID- 17523309
TI  - A histopathological study on combined hepatocellular and cholangiocarcinoma:
      cholangiocarcinoma component is originated from hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Combined hepatocellular and cholangiocarcinoma of the liver is
      relatively infrequent, and its pathogenesis remains obscure. The aim of this
      study is to investigate its clinical and pathological features and proliferative
      activity. METHODOLOGY: In this study, we investigated the histopathological
      features, Ki-67 labeling index, and p53 immunohistochemistry of 18 surgically
      resected cases of combined hepatocellular and cholangiocarcinoma among 1102
      consecutive cases of surgically resected primary liver cancers. All tumors were
      compatible with the WHO definition of this tumor. Microscopically, we classified
      the cases into the following three categories according to the arrangement of the
      hepatocellular carcinoma and cholangiocarcinoma components; (1) Type I in which
      hepatocellular carcinoma and cholangiocarcinoma formed nodules that could easily
      be distinguished from each other, (2) Type II in which the both components were
      finely mixed, so that the two components were almost indistinguishable, and (3)
      Type III in which the tumors had lobular structures with hepatocellular
      carcinomas existing centrally and cholangiocarcinomas existing peripherally.
      RESULTS: Microscopically, the tumors were classified into type I 7 tumors, type
      II 5 tumors, and type III 6 tumors. In one case of type I, well differentiated
      hepatocellular carcinoma demonstrated cholangiocarcinoma in "nodules-in-nodules"
      fashion. The average of Ki-67 labeling index of hepatocellular carcinoma
      component of combined hepatocellular and cholangiocarcinoma was 4.4 +/- 3.4% and
      the index of cholangiocarcinoma component was 11.0 +/- 8.5%, which is
      significantly higher than that of the hepatocellular carcinoma component. On p53
      immunohistochemistry, 5 of 18 cases (29.4%) were positive. In one case, the
      cholangiocarcinoma component was positive for p53, but the hepatocellular
      carcinoma component was negative. In the other 4 cases, both the hepatocellular
      carcinoma and cholangiocarcinoma components were positive. CONCLUSIONS:
      Microscopically, type III seems to be a feature of metaplasia or proliferation of
      bipotential progenitor cells. Metaplasia of hepatocellular carcinoma to
      intrahepatic cholangiocarcinoma is assumed to be one of the pathogenic pathways
      of combined hepatocellular and cholangiocarcinoma.

PMID- 17523310
TI  - The diagnostic values of measuring the liver volume in detecting occult hepatic
      metastases from colorectal cancer.
AB  - BACKGROUND/AIMS: Some studies have shown the reduction of portal blood flow in
      patients with occult hepatic metastases, which may lead to a decrease in the
      liver volume. The aim of this study was to assess volumetric changes of the liver
      with occult colorectal metastases. METHODOLOGY: Sixty-three consecutive patients
      with colorectal cancer who underwent curative resection were studied
      retrospectively. The ratio of the preoperative computerized tomography (CT)
      estimated liver volume to the standard liver volume (CV/SV ratio) was calculated
      as a uniform parameter to compare the volume between the liver with and without
      occult hepatic metastases. RESULTS: The CT-estimated liver volume was 841 +/- 102
      (mean-SD) mL in 8 patients who subsequently developed overt hepatic metastases
      during a 2-year follow-up and 1145 +/- 232 mL in 55 patients without metastases
      (p = 0.0004). The CV/SV ratio was significantly smaller in patients with
      metachronous hepatic metastases than in those without (0.78 +/- 0.09 versus 1.02
      +/- 0.14; p < 0.0001). CONCLUSIONS: The results suggest the possibility that the
      liver with occult colorectal metastases decreases in size before metastatic
      tumors develop to be detectable with conventional imaging techniques. The
      measurement of the CV/SV ratio may be of value in detecting occult hepatic
      metastases from colorectal cancer.

PMID- 17523311
TI  - Hepatic arterial infusion of 5-fluorouracil in combination with subcutaneous
      interferon-alpha for advanced hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Transcatheter arterial chemoinfusion (TACI) is the main
      therapeutic modality for advanced hepatocellular carcinoma (HCC) with portal
      thrombus. However, TACI is not sufficient to improve prognosis. In this study, we
      evaluated the response to hepatic arterial infusion of 5-fluorouracil (5-FU) in
      combination with subcutaneous interferon (IFN)-alpha in patients with advanced
      HCC. METHODOLOGY: Ten patients (men, 8; women, 2; mean age, 55-77) with advanced
      HCC were enrolled in this study. Hepatic arterial infusion of 5-FU (500 mg/24
      hrs) was performed for 5 days on the first and second week. IFN-alpha (5 x 10(6)
      International Units) was subcutaneously administered three times a week for 4
      weeks (1 therapeutic course). Response to therapy was evaluated by abdominal
      computed tomography at the end of two courses of therapy. RESULTS: Seven patients
      received more than two courses of therapy. One patient (14%) showed complete
      response (CR). Four patients had stable disease (SD) (57%) and the remaining 2
      patients had progressive disease (PD) (29%). Tumor markers decreased in all
      patients except 1 with PD. The 6-month survival rate was 40%. Therapy was
      discontinued in 3 patients due to severe adverse effects; all of these patients
      were over 70 years old, and had moderate liver dysfunction (Child-Pugh score of
      Grade B) before initiation of therapy. CONCLUSIONS: The goal of the therapy with
      hepatic arterial infusion of 5-FU in combination with subcutaneous IFN-alpha was
      attained in only 14% among our advanced HCC patients. The tumor completely
      disappeared in 1 patient, suggesting that this therapeutic modality may be of
      potential benefit in advanced HCC patients. However, this therapy should be
      performed with caution in patients with poor hepatic function (grade B or C of
      Child-Pugh score) and in those more than 70 years old.

PMID- 17523312
TI  - The effects of a cyclooxygenase-2 inhibitor, FK3311, on total hepatic ischemia
      reperfusion injury of the rat.
AB  - BACKGROUND/AIMS: This study was designed to investigate the effects of a
      selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury
      of the rat liver. METHODOLOGY: Male Sprague-Dawley rats were used in this
      experimental study. Total hepatic ischemia was induced with a clamping portal
      triad. The animals were divided into two groups: the control group and the FK
      group, in which FK3311 (FK, 1.0 mg/kg) was administered via the penile vein. The
      serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      and lactate dehydrogenase (LDH) were measured 2 h after reperfusion, while those
      of thromboxane (Tx) B2 and 6-ketoprostaglandin (PG) F1alpha (stable metabolites
      of TxA2 and PGI2) were measured 30 min after reperfusion. The liver tissue blood
      flow was measured at preischemia, end-ischemia, and 30, 60, 90, and 120 min after
      reperfusion. The liver tissues obtained from animals at 2h after reperfusion were
      excised for histopathology. RESULTS: The serum levels of AST, ALT, and LDH were
      significantly lower in the FK group than in the control group. Similarly, in the
      FK group, the serum levels of TxB2 were significantly lower than in the control
      group. By contrast, the 6-keto-PG F1a levels were not significantly reduced. The
      liver tissue blood flow at 120 min after reperfusion was significantly higher in
      the FK group than in the control group. The histopathological study showed that
      hepatic tissue damage was milder in the FK group than in the control group.
      CONCLUSIONS: FK has protective effects on hepatic ischemia-reperfusion injury
      stemming from the marked inhibition of TxA2.

PMID- 17523313
TI  - Selective hepatic vascular exclusion for the hepatic resection of HCC.
AB  - BACKGROUND/AIMS: Selective hepatic vascular exclusion (SHVE) is an effective
      technique for the control of bleeding in major hepatic resections. Outcomes of
      the procedures of the SHVE group were compared with the non-SHVE group.
      METHODOLOGY: A retrospective study was carried out of 312 hepatic resections
      performed over a period of 10 years. The cases in this study were limited to
      Child's classification A, because of the rate of Child A in the SHVE group (n=82)
      was significantly higher than that within the non-SHVE group (n=158) (93% vs.
      71%; p < 0.001). Preoperative factors, like age, gender, tumor size,
      intraoperative blood loss, operation time, and the postoperative course of the
      two groups were compared for both groups. RESULTS: The SHVE group showed
      significantly less blood loss, necessary blood transfusion, and a significant
      rate of severe postoperative complications. The rate of segmentectomy and
      subsegmentectomy in the SHVE group was higher than in the non-SHVE group, and the
      rate of partial hepatectomy and lobectomy in the non-SHVE group was higher than
      that in the SHVE group. Although the more difficult operations were performed in
      the SHVE group than in the non-SHVE group, there was no significant difference in
      the postoperative hospital stays in both groups. CONCLUSIONS: The SHVE technique
      is effective for bleeding control in major liver resections.

PMID- 17523314
TI  - Extrahepatic control of the middle hepatic vein with inflow control by pedicle
      clamping in major liver surgery.
AB  - Surgical techniques commonly used for controlling bleeding during major liver
      surgery are hepatic inflow occlusion (Pringle maneuver) or total hepatic vascular
      exclusion (THVE), which are effective procedures of diminishing intraoperative
      blood loss. However, it is difficult to control retrograde bleeding from the
      hepatic veins using Pringle maneuver and some patients do not tolerate
      hemodynamic changes caused by THVE. We isolated the left and middle hepatic veins
      separately using Arantius' ligament approach to these hepatic veins, and
      extrahepatic control of the relevant to the liver segment to be resected hepatic
      veins with inflow control by Glissonian pedicle clamping was successfully
      performed.

PMID- 17523315
TI  - A case of hepatic angiosarcoma surviving for more than 16 months after hepatic
      resection.
AB  - Hepatic angiosarcoma is a non-epithelial malignant tumor and a rare primary
      neoplasm accounting for only a 0.1% of primary liver malignant tumors. Hepatic
      angiosarcoma progresses rapidly; therefore, most cases are discovered at an
      advanced stage, and less than 20% of the patients have received surgery. The lack
      of specific symptoms and radiological findings leads to the delay of diagnosis
      resulting in the poor prognosis. To the best of our knowledge, only three
      patients have been reported to survive for more than one year after hepatic
      resection for angiosarcoma. We herein report a patient with hepatic angiosarcoma,
      4 cm in size, who underwent hepatic resection after confirming the diagnosis as
      angiosarcoma by the intraoperative frozen section examination. The patient is
      still alive for more than 16 months postoperatively without any signs of
      recurrence.

PMID- 17523316
TI  - Anterior transhepatic approach for hepatocellular carcinoma located in deep
      positions of segment VIII.
AB  - Liver resection for liver tumors located in deep positions in segment VIII
      remains a technical challenge. We successfully resected a hepatocellular
      carcinoma located in deep position in segment VIII and extended into the
      paracaval portion of the right caudate lobe, using an anterior transhepatic
      approach. The patient was a 73-year-old man with chronic hepatitis C.
      Preoperative ultrasonography and dynamic computed tomography revealed that the
      tumor was about 3.0 cm in diameter and close to the roots of the middle and right
      hepatic veins and the paramedian Glissonian pedicle. The right anterior artery
      was supplying the tumor. The liver was opened along the right side of the middle
      hepatic vein. The dorsal Glissonian pedicle of segment VIII was easily exposed,
      ligated, and divided. The dorsal part of segment VIII was removed, along with the
      paracaval portion of the right caudate lobe. The postoperative course was
      uneventful. The patient was disease-free 17 months after surgery. This anterior
      transhepatic approach provides a wide operating field and easy hemostasis, and
      could preserve the liver parenchyma as much as possible in a patient with liver
      dysfunction.

PMID- 17523317
TI  - Living donor hepatectomy in a pregnant woman.
AB  - Liver transplantation with a live donor is an effective way to expand the donor
      pool. Restrictive selection of living donors may assure donor safety but limit
      the utility of this resource. A 12-month-old recipient with biliary atresia was
      rapidly deteriorating with hepatic encephalopathy, massive ascites and
      coagulopathy. Her mother, the only possible living donor, expressed a strong
      desire to donate part of liver to her baby, although she was found to be
      pregnant. The donor hepatectomy was then undertaken at 18 weeks of gestation. A
      left lateral segmentectomy was performed. Her postoperative course was uneventful
      and she was discharged 7 days after the operation. She gave birth to a healthy
      term baby without any complications 5 months later. Both recipient and her
      younger brother are well 12 months after the operation. Despite the limited
      experience reported herein, pregnancy may no longer be considered an absolute
      contraindication for live liver donation.

PMID- 17523319
TI  - Hepatitis B today.
AB  - Hepatitis B remains a major problem for public health worldwide and represents a
      challenging disease for practicing physicians. Of the 2 billion people who have
      been infected with the hepatitis B virus, more than 350 million have chronic
      infections. These chronically infected individuals are at high risk of death from
      cirrhosis and liver cancer. The use of new antiviral drugs, such us nucleotides
      analogues, offer good hope in the prognosis of patients suffering from chronic
      hepatitis B.

PMID- 17523318
TI  - Use of an interpositional venous graft posterior to the pancreas for LDLT
      patients with portal vein thrombosis.
AB  - Portal vein thrombosis is a risk factor in patients who require liver
      transplantation, because it is often difficult to treat portal vein thrombosis,
      especially when it involves the confluence of the superior mesenteric vein and
      splenic vein. Since some transplant centers that perform living-donor liver
      transplantation do not have cryopreserved cadaveric vein grafts available and do
      not use graft veins that are long enough for a jump graft, it is difficult to
      reconstruct the portal vein with interpositional vein grafts in patients with
      portal vein thrombosis. We describe the treatment of portal vein thrombosis with
      an interpositional vascular graft posterior to the pancreas in a living-donor
      liver transplantation patient without using a jump graft. This method provided a
      shorter rout between the donor and recipient portal vein than a jump graft. Our
      experience suggests that this solution can be helpful in treating portal vein
      thrombosis.

PMID- 17523320
TI  - Extended lymphadenectomy in cephalic pancreatoduodenectomy. Personal
      observations.
AB  - BACKGROUND/AIMS: Long-term survival in patients with cancer of the pancreatic
      head is disappointing. Surgery is the only curative therapy. Unfortunately the
      prognosis of resected patients (10-15%) is extremely poor due to loco-regional
      cancer recurrence (50%). Lymphatic and perineural invasion may account for local
      recurrence. Japanese studies have reported the importance of an extended
      lymphadenectomy during the classic Whipple exeresis (40% of patients present
      lymph node metastases). METHODOLOGY: At the General Surgical Clinic of Pavia
      University 20 patients (14 men, 6 women, mean age 62.4 yr) with pancreatic head
      cancer (17 adenocarcinoma, 1 lymphoma, 2 carcinoma) underwent Whipple's exeresis
      with a regional (peripancreatic or R1) and juxta-regional (para-aortic or R2)
      lymphadenectomy according to the Ishikawa technique, between 1996-2000. R1 nodes
      consisted of lymph nodes at the pylorus, superior pancreatic head, common bile
      duct, anterior pancreaticoduodenal region, inferior pancreatic head and superior
      mesenteric vessels. R2 nodes consisted of lymph nodes at the superior and
      inferior pancreatic body, mid colic region, common hepatic duct, celiac axis and
      para-aortic region. RESULTS: The wide dissection was quite easy in patients with
      a serious cholestatic disease. Intraoperative mortality was 0%. Operative
      mortality was 5%. Postoperative complications (20%) consisted of 1 sepsis, 1
      hepato-renal syndrome with hepatic coma, 1 intestinal obstruction by adhesive
      bands, and 1 wound infection. Eight patients (40%) died during a mean follow-up
      period of 6 months (neoplastic recurrence 50%). Notwithstanding the advanced
      disease (stage III 50%; N1+ 50%), 12 patients (60%) had a median postoperative
      survival rate of 18.4 months (range 1-48 months) without neoplastic recurrence.
      Tumor diameter was less than 4cm in 83.3% of cases. CONCLUSIONS: An earlier
      diagnosis (with tumor diameter <4 cm) can improve pancreatic head cancer
      prognosis. A wide surgical exeresis with R2 lymph nodes clearance together with
      surrounding connective and nervous tissue can remove micrometastases and better
      control local recurrence.

PMID- 17523321
TI  - The value of serum amylase and elastase measurements in the prediction of post
      ERCP acute pancreatitis.
AB  - BACKGROUND/AIMS: Acute pancreatitis is the most serious complication of
      endoscopic retrograde cholangiopancreatography (ERCP) but is not very common. A
      test that could predict the occurrence of pancreatitis would help to decide
      whether to discharge a patient after ERCP or not. The aim of this prospective
      study was to compare the value of serum amylase and elastase in the prediction of
      post-ERCP pancreatitis and its severity. METHODOLOGY: Ninety-seven patients
      underwent ERCP. Serum samples were taken before, two and six hours after ERCP for
      amylase and elastase measurement. Fifty-four patients (group A) were treated with
      continuous intravenous infusion of octreotide, beginning 6 hours before ERCP and
      terminating 24 hours after. Forty-three patients (group B) received no preventive
      treatment. RESULTS: In group A, 9 patients (16.6%) developed pancreatitis, 8 of
      them (14.8%) mild and 1 (1.8%) severe. Two patients in group B developed mild
      pancreatitis (p = 0.1). In all patients the predictive accuracy in the second
      hour for amylase >3N, >5N and elastase >N was 79%, 87% and 86% respectively. The
      likelihood ratio of positivity (LRP) was 3.6, 6.5 and 6.1. In the sixth hour the
      respective values were 76%, 86%, 85% and 4, 7.3 and 6.4. In group A, the
      respective values in the second hour were 85%, 91%, 94% and 5, 25.2, infinity,
      and in the sixth hour 85%, 94%, 98% and 5.7, 11.5, infinity. CONCLUSIONS: Serum
      amylase (with cutoff value >5N) and elastase (>N), 6 hours after ERCP, were the
      most accurate tests for the prediction of post-ERCP pancreatitis, especially in
      patients receiving octreotide. The measurement of serum elastase could supplement
      that of serum amylase in the prediction of more cases of post-ERCP pancreatitis.

PMID- 17523322
TI  - An endoscopic sphincterotomy of the minor papilla in the management of
      symptomatic pancreas divisum.
AB  - BACKGROUND/AIMS: The efficacy of endoscopic treatment in pancreas divisum remains
      controversial. This study evaluated the results of an endoscopic sphincterotomy
      of the minor papilla and temporary transpapillary pancreatic stenting in patients
      with pancreas divisum. METHODOLOGY: Pancreas divisum was diagnosed in four
      patients between 1994 and 2004. All patients demonstrated episodes of recurrent
      upper abdominal and back pain were with a median follow-up period of 14.5 months.
      One patient was treated by a sphincterotomy of the minor papilla alone, while
      three others also underwent transpapillary pancreatic stent insertion for seven
      days. RESULTS: A Sphincterotomy of the minor papilla could be successfully
      achieved in all patients. There was no instance of bleeding, perforation or
      sepsis after the procedure. The postoperative serum amylase level in the patients
      without stent insertion (1352 IU/L) was higher than that the patients with stents
      (mean level 515 IU/L, range 358 to 680). The dilatated dorsal pancreatic ducts
      were found to improve after a sphincterotomy in all patients. None of the
      patients had any further episodes of pancreatitis. In addition, all patients
      demonstrated a considerable improvement in their upper abdominal or back pain
      symptoms, which did not require either analgesic medication or hospitalization.
      CONCLUSIONS: An endoscopic sphincterotomy and temporary transpapillary pancreatic
      stenting were therefore suggested to be a beneficial treatment modality for
      patients with pancreas divisum.

PMID- 17523323
TI  - Clinical results of extended lymphadenectomy and intraoperative radiotherapy for
      pancreatic adenocarcinoma.
AB  - BACKGROUND/AIMS: The efficacy of extended lymphadenectomy and intraoperative
      radiotherapy for resectable pancreatic cancer is controversial. The objective of
      this study was to clarify the surgical outcome after pancreatic resection with
      extended lymphadenectomy or intraoperative radiotherapy in patients with
      pancreatic adenocarcinoma. METHODOLOGY: Between 1992 and 2002, 105 patients with
      pancreatic adenocarcinoma undergoing surgical resection were retrospectively
      analyzed. Eighty-eight patients had invasive ductal adenocarcinoma and 17 had
      invasive intraductal papillary mucinous adenocarcinoma. Seventy-six patients
      underwent pancreatic resection with extended lymphadenectomy and 44 received 20
      Gy intraoperative radiotherapy. RESULTS: Patients with invasive intraductal
      papillary mucinous adenocarcinoma had a similar prognosis to those with invasive
      ductal adenocarcinoma. There was no significant difference in survival (p = 0.86)
      between patients with and without extended lymphadenectomy. There was no
      significant difference in survival (p = 0.053) between patients with and without
      intraoperative radiotherapy. Patients without lymph node metastasis had a
      significantly better prognosis (p = 0.0015) than those with nodal involvement.
      CONCLUSIONS: Neither extended lymphadenectomy nor intraoperative radiotherapy
      showed a survival advantage in patients with resectable pancreatic
      adenocarcinoma. Pancreatic cancer patients without nodal involvement had a
      significantly better prognosis than those with nodal involvement.

PMID- 17523324
TI  - Lesser-sac lavage for intraoperative detection of blunt pancreatic duct injury.
AB  - BACKGROUND/AIMS: Blunt pancreatic duct injury is difficult to differentiate,
      especially during surgery. In terms of demonstration of pancreatic duct injury,
      endoscopic retrograde pancreatography (ERP) is the gold standard imaging study,
      however, availability can be problematic. Therefore, we have designed a method
      utilizing lesser-sac lavage to differentiate pancreatic duct injury. METHODOLOGY:
      Patients sustaining blunt pancreatic trauma treated at our institution over a two
      year period were retrospectively enrolled in this study. Based on computed
      tomography (CT), these patients were divided into two groups: deep laceration or
      complete transection (Group 1) and superficial laceration (Group 2).
      Additionally, ten patients sustaining blunt abdominal trauma who had undergone
      emergency laparotomy for other visceral organ injury (Group 3) and four
      undergoing pancreatoduodenectomy (Group 4) were selected as controls. For
      laparotomy in Groups 1-3, the lesser sac was opened for lavage, with 50 mL of
      0.9% normal saline inserted, and 3mL of the sample fluid withdrawn at four time
      points (15, 30, 45 and 60 mins) with the fluid immediately replaced with 3 mL of
      saline. Lavage-ascites amylase (LAA) and lipase (LAL) levels were measured. Serum
      amylase and lipase activities were measured intraoperatively from 3mL of the
      patient's blood. RESULTS: Over the two-year study period, there were four
      pancreatic duct transections (Group 1), five partial pancreatic lacerations
      confirmed by post-ERP CT (Group 2), ten non-pancreatic traumas (Group 3), and
      four pancreatoduodenectomies due to pancreatic-head cancer (Group 4). The LAA and
      LAL for Group 1 were significantly higher than those for Group 2 or 3 at each of
      the four time points. The LAA and LAL ratios for Group 1 relative to Group 2 or 3
      decreased gradually over time. These LAA ratios ranged from 7-13 for Group 1 to
      Group 2, 138-232 for Group 1 to Group 3, and 17-21 for Group 2 to Group 3. By
      contrast, the LAL ratio ranged from 3.0-3.4 comparing Group 1 to Group 2, 3180
      29124 for Group 1 to Group 3, and 1058-8705 for Group 2 to Group 3. CONCLUSIONS:
      Using lesser-sac lavage for measurement of LAA and LA L constitutes a rapid, non
      invasive and effective method for detection of pancreatic duct injury, especially
      transection of the main duct. LAA appears to be a better indicator for
      differentiation of minor (superficial laceration or side branch) or major (MPD)
      pancreatic injury at the first time point (15 minutes post lavage) compared to
      LAL. By contrast, LAL appears to be a better indicator with respect to
      differentiation of the injured pancreas from the normal organ at this time point.

PMID- 17523325
TI  - Relation between chronic pancreatitis and pancreatic cancer in the light of
      surgical management.
AB  - BACKGROUND/AIMS: Relation between cancer of the exocrine part of the pancreas and
      chronic pancreatitis has not been clearly defined and the problem of carcinogens
      based on long-lasting chronic pancreatitis is still a matter of discussion.
      METHODOLOGY: The aim of the study was analysis of postoperative material of
      patients who in the years 1999-2003 underwent either drainage procedures (n=49)
      in the course of chronic pancreatitis or resectional procedures (n=36) for
      chronic pancreatitis or pancreatic cancer. RESULTS: In the group of patients with
      drainage procedures pancreatic cancer was histologically detected in
      postoperative material (specimens collected from the wall of pancreatic
      pseudocyst or dilated main pancreatic duct) in 3 patients (6.1%). In the group of
      patients with long-lasting chronic pancreatitis who underwent a resectional
      procedure pancreatic cancer was postoperatively detected in 4 cases (30.7%).
      CONCLUSIONS: Analysis of presented material confirms that long-lasting chronic
      pancreatitis predisposes to cancer of the exocrine part of the pancreas. This
      indicates that risk of pancreatic cancer should be taken into consideration in
      each patient with long lasting chronic pancreatitis.

PMID- 17523326
TI  - Management of pancreatic trauma and its consequences--guidelines or individual
      therapy?
AB  - BACKGROUND/AIMS: Diagnosis of pancreatic trauma and its complications may be
      difficult due to non-specific signs and symptoms and treatment recommendations
      are not unequivocal. METHODOLOGY: Clinical data of a series of 47 patients with
      pancreatic trauma were analyzed; most of them were polytraumatized and treated by
      an interdisciplinary team. RESULTS: The most common causes were traffic accidents
      and sport injuries with 66% and 15%, respectively. Concomitant injuries were seen
      in 96% (nonpancreatic intra-abdominal injuries 85% including spleen 38% and liver
      34%, extra-abdominal injuries 70%). Concomitant liver injuries were treated
      conservatively in 31% and operatively in 69% (including hepatic packing in 38%).
      Concomitant splenic injuries were usually very severe and could be managed
      conservatively in only 11%. All patients with pancreatic injuries grade III, IV
      or V (17%) according to the American Association of Surgical Trauma
      Classification required surgery, endoscopic treatment or interventional
      radiology. The most common posttraumatic complications were necrotizing
      pancreatitis (15%), pseudocyst formation (9%), abscesses (6%) and fistulas (4%).
      CONCLUSIONS: The status of the pancreatic duct is the crucial point for
      management of pancreatic trauma and should be assessed as early as possible.
      Treatment has to be tailored to the individual situation, especially in patients
      with severe concomitant injuries or prolonged course.

PMID- 17523327
TI  - Late postoperative complications in patients with pancreaticobiliary maljunction.
AB  - BACKGROUND/AIMS: Reports on the late postoperative complications in patients with
      pancreaticobiliary maljunction (PBM) are limited. METHODOLOGY: Eighteen PBM
      patients with biliary dilatation and 12 without biliary dilatation were
      surgically treated at our institute. These 30 PBM patients were retrospectively
      reviewed, with particular attention to late postoperative complications. RESULTS:
      Nineteen patients without biliary malignancies underwent resection of the
      extrahepatic bile duct (BD) and hepaticojejunostomy. Two patients without biliary
      dilatation or malignancy underwent cholecystectomy alone. Nine patients with
      malignancies underwent hepatectomy with extrahepatic BD resection in 7 patients,
      pancreatoduodenectomy (PD) in 1, and PD + hepatectomy in 1. The median follow-up
      duration was 110 months. All patients without malignancies are presently alive in
      good healthy condition and have not developed any malignancy postoperatively.
      Late postoperative complications were seen in 6 (20%). Four patients with biliary
      dilatation were surgically or endoscopically treated for intrahepatic lithiasis
      3, 12, 42 and 54 months after initial operation. One of them had a pancreatic
      protein plug 216 months after surgery, and was treated with papilloplasty after
      open laparotomy. In one patient without biliary dilatation, pancreatic protein
      plug and intrahepatic lithiasis were found 60 and 72 months after surgery,
      respectively, and both were treated endoscopically. CONCLUSIONS: Intrahepatic
      lithiasis and pancreatic protein plug are frequent late postoperative
      complications. The intrapancreatic residual choledochus or dilated pancreatic
      duct seems to be related to pancreatic protein plug. However, intrahepatic
      lithiasis may occur regardless of the pattern of the biliary tract dilatation.
      Careful, long-term follow-up is important in patients with PBM.

PMID- 17523328
TI  - Synbiotic control of inflammation and infection in severe acute pancreatitis: a
      prospective, randomized, double blind study.
AB  - BACKGROUND/AIMS: Experimental and clinical studies demonstrated that probiotics
      containing lactobacilli significantly improve the outcome of acute pancreatitis.
      In a prospective, randomized, double-blinded study the role of "Synbiotic 2000",
      a new synbiotic composition with high colony forming unit (CFU) was evaluated in
      the treatment of severe acute pancreatitis. METHODOLOGY: Patients with severe
      acute pancreatitis were randomized into two groups. Nasojejunal feeding was
      commenced within 24 hours after admission in both groups and continued for at
      least seven days. The first group of patients received four different
      lactobacilli preparations with 1010 CFU, respectively, and prebiotics containing
      four bioactive fibers (inulin, beta-glucan, resistant starch and pectin) in
      addition. Patients in the second (control) group received only prebiotics.
      RESULTS: 62 patients with severe acute pancreatitis completed the study.
      Altogether 8 patients died. Lower incidence of multiorgan failure (MOF), septic
      complications and mortality were detected in the first group compared to the
      control, but the differences were not significant statistically. The total
      incidence of systemic inflammatory response syndrome (SIRS) and MOF were
      significantly different between the two groups (8 vs. 14; p < 0.05). Furthermore,
      the number patients recovering with complications were significantly less in the
      first group receiving modern synbiotic therapy compared to the control (p <
      0.05). Finally, lower rate of late (over 48 hours) organ failure was detected in
      the first versus the control group (3.0% vs. 17.2%). CONCLUSIONS: The results
      suggest that early nasojejunal feeding with synbiotics may prevent organ
      dysfunctions in the late phase of severe acute pancreatitis. In addition, the
      data also indicate that the infection of pancreatic necrosis may be associated
      with early phase organ failure.

PMID- 17523329
TI  - Celiac axis occlusion of a patient undergoing pancreaticoduodenectomy after
      distal gastrectomy.
AB  - In patients with celiac axis occlusion, performance of pancreaticoduodenectomy
      involves sacrifice of the gastroduodenal artery which results in a risk of hepato
      pancreato-biliary and other organic ischemia. Celiac axis occlusion does not
      recently seem an uncommon finding in cases of pancreaticoduodenectomy but
      diagnosis of celiac axis occlusion may be difficult in patients with former
      abdominal surgery. The present case report shows a patient with pancreatic head
      adenocarcinoma, in whom a preoperative diagnosis of celiac axis occlusion was not
      proved because of displacement of the celiomesenteric arterial branches based on
      former distal gastrectomy with Kocher's maneuver. A 56-year-old man with
      malignant obstruction of the lower bile duct was referred to our hospital for
      undergoing pancreaticoduodenectomy. In his past history, the patient had
      undergone distal gastrectomy reconstructed with Billroth I method due to gastric
      ulcer. In preoperative abdominal angiography, the celiac axis was not detected at
      the normal position and was incorrectly recognized to be anomalously originated
      from the superior mesenteric artery. During surgery, hepatic arterial flow was
      markedly diminished by clamping of the gastroduodenal artery. Celiac axis
      occlusion was then proved and the thick and tight median arcuate ligament was
      detected. Hepatic arterial blood flow was recovered by a complete division of the
      median arcuate ligament. Postoperative course of the patient was uneventful. In
      cases of pancreaticoduodenectomy, careful preoperative angiographic diagnosis is
      needed for patients with celiac axis occlusion who have undergone former gastric
      surgery because the celio-mesenteric arterial branches have been displaced by
      Kocher's maneuver. The present report also demonstrates another patient with a
      typical celiac axis stenosis.

PMID- 17523330
TI  - Huge pseudocyst of the pancreas caused by poorly differentiated invasive ductal
      adenocarcinoma with osteoclast-like giant cells: report of a case.
AB  - A 72-year-old man presented with several week's abdominal distension and
      jaundice. Under the tentative diagnosis of pancreatic pseudocyst of 22cm in
      diameter, a percutaneous drainage was performed. Despite the reduction of the
      pseudocyst, his serum total bilirubin level was increased. At this time,
      abdominal computed tomography scan showed a tumor at the uncinate process of the
      pancreas. After the biliary decompression, a total pancreatectomy with the
      resection of pseudocyst walls and splenectomy was performed. It was
      histologically proven to be poorly differentiated ductal adenocarcinoma in
      combination with osteoclast-like giant cells. The pseudocyst was considered to be
      due to the stenosis of the main pancreatic duct caused by carcinoma of the
      uncinate process. Five months later, he died of recurrent carcinomatous
      peritonitis. Osteoclast-like giant cell tumor is a very rare neoplasm, the origin
      and prognosis of which still remain obscure. However, it has to be considered in
      the differential diagnosis of cystic changes of the pancreas, especially of
      pseudocyst. Furthermore, detailed surveys are needed in cases of pseudocyst of
      the pancreas without chronic pancreatitis, in order to identify small carcinoma
      of the pancreas.

PMID- 17523331
TI  - Prediction of lymph node metastasis by size of early gastric carcinoma.
AB  - BACKGROUND/AIMS: Tumor size requires more investigation as a factor in
      determining extent of regional lymph node dissection in early gastric carcinoma.
      We retrospectively investigated 573 patients with such tumors to identify
      predictors of lymph node metastasis. METHODOLOGY: Postoperative survival was
      examined for groups of patients defined by tumor size under 2 cm, between 2 and
      4cm, and over than 4cm. Factors predicting tumor recurrence and regional lymph
      node metastasis also were determined. RESULTS: Postoperative survival of patients
      with tumors larger than 4 cm was significantly worsethan that of patients with
      tumors smaller than 2 cm. Multivariate analysis identified lymph node metastasis
      as a significant risk factor for recurrence of early gastric carcinoma, while
      identifying primary tumor size and lymphatic vessel involvement as significant
      risk factors for lymph node metastasis. CONCLUSIONS: Lymph node metastasis, which
      increased risk of postoperative recurrence in early gastric carcinoma, was
      related to tumor size.

PMID- 17523332
TI  - Single center experience of laparoscopic vs. open resection for gastrointestinal
      stromal tumors of the stomach.
AB  - BACKGROUND/AIMS: With better understanding of disease biology and technological
      advances, an increasing number of gastric gastrointestinal stromal tumors (GISTs)
      are being resected laparoscopically. We assessed our management of gastric GISTs
      in our institution. METHODOLOGY: Prospectively collected data from 13 patients
      who underwent surgery for gastric gastrointestinal stromal tumors over an 18
      month period were analyzed with respect to operative and oncological outcomes.
      Seven patients underwent open resection and 6 patients had laparoscopic
      resection. RESULTS: The tumors were evenly distributed in both groups in whom the
      median age was 68 years in the open group vs. 70 years in the laparoscopic group.
      The median operating time was 132 min in the open group and 110 min in the
      laparoscopic group and patients who had a laparoscopic resection had a shorter
      hospital stay (4 days versus 11 days). Patients in the open group had a larger
      tumor the patients in the laparoscopic group (11.5 x 6 x 4 cm vs. 5 x 4 x 3 cm).
      No patient had evidence of recurrence at median follow-up of 9 months.
      CONCLUSIONS: Patients with small gastric GISTs can be safely resected with a
      laparoscopic approach, offering a quicker operation and shorter hospital stay. A
      laparoscopic approach does not alter risk of early local or distant recurrence.

PMID- 17523333
TI  - Clinicopathological investigation of early gastric carcinoma; is less invasive
      surgery right for early gastric carcinoma?
AB  - BACKGROUND/AIMS: The detection of early gastric carcinoma (EGC) has increased
      worldwide in recent years due to advances in endoscopic techniques and equipment.
      The objectives of this study were to compare the clinicopathological findings of
      patients with N1 node-negative and positive EGC, and then consider the treatment
      options. METHODOLOGY: A total of 814 cases of gastric carcinoma in patients who
      underwent surgical procedures between 1981 and 1999 at Kochi Medical School were
      studied. In 375 patients with EGC, surgicopathological parameters were analyzed.
      RESULTS: Lymph node metastasis was observed in 28 patients (7.4%) with EGC. EGC
      of the flat type with submucosal invasion, lymphatic permeation, and tumor size
      larger than 4 cm was associated with higher risk factors of lymph node
      metastasis. In this study, the location and histological classification of EGC
      were not related to lymph node metastasis. However, lymph node metastasis was not
      recognized in submucosal invasive gastric carcinomas less than 1 cm in size.
      CONCLUSIONS: In the EGC limited to the mucosa or smaller than 1 cm, when the
      tumor infiltrated the submucosal layer, it could be managed by less invasive
      surgery without standard lymphadenectomy, and gastrectomy with lymphadenectomy
      was necessary for patients with EGC who had a high risk of lymph node metastasis.

PMID- 17523334
TI  - The relationship between gastric emptying determined by the breath test and H.
      pylori.
AB  - BACKGROUND/AIMS: Helicobacter pylori infection has been implicated in atrophic
      gastritis and gastric ulcer disease. However, the relationship between gastric
      emptying and Helicobacter pylori infection is still unclear. METHODOLOGY: One
      hundred and two consecutive patients with functional dyspepsia were enrolled in
      this study (53 Helicobacter pylori positive and 49 negative). Gastric emptying
      was determined using both the 13C-octanoic acid breath test and the paracetamol
      absorption test. For grading gastric atrophy, the biopsy samples and serum
      pepsinogen I/II ratio were used. The relationship between gastric emptying,
      Helicobacter pylori infection and atrophy grade was investigated. RESULTS: There
      was no significant difference in all gastric emptying parameters between
      Helicobacter pylori positive and negative patients. However, in Helicobacter
      pylori positive subjects, pepsinogen I/II ratio correlated with atrophy grade,
      and it also correlated with all parameters of gastric emptying. Especially in the
      half-emptying time, an important parameter, there was significant correlation
      with the pepsinogen I/II ratio (R = -0.39, p < 0.01). This finding implies that
      gastric emptying is delayed according to the degree of gastric atrophy.
      CONCLUSIONS: Gastric emptying was not delayed simply according to advanced age,
      but according to the advance in gastric atrophy.

PMID- 17523335
TI  - Anastomotic dehiscence after gastrectomy for cancer. Personal series.
AB  - BACKGROUND/AIMS: Nowadays the risk of anastomotic dehiscence after gastrectomy
      still exists. So the aim of this study was to analyze our experience regarding
      these anastomoses. METHODOLOGY: In our Surgical Unit, which is located in the
      Department of Surgical Sciences, Organ Transplantation and Advanced Technologies
      of the University of Catania, from January 1st 1985 to December 31st 2000, 249
      patients underwent surgery for gastric cancer. RESULTS: We observed a
      statistically significant decrease of leaks in the third period of our study.
      CONCLUSIONS: These data demonstrate a significant decrease of anastomotic leaks
      with stapler in comparison to manual anastomoses.

PMID- 17523336
TI  - Recurrence in early gastric cancer--presence of micrometastasis in lymph node of
      node negative early gastric cancer patient with recurrence.
AB  - BACKGROUND/AIMS: There are cases of recurrence even after curative resection in
      early gastric cancer. METHODOLOGY: Seven hundred and sixty-five patients with
      early gastric cancer who underwent curative gastrectomy were analyzed to identify
      the prognostic factor. Micrometastases within lymph nodes were determined by
      immunohistochemistry using anti-cytokeratin antibody in node-negative early
      gastric cancer patients with recurrence. RESULTS: The recurrence was observed in
      17 patients. Hematogenous recurrence was observed most frequently (47.1%),
      followed by peritoneal recurrence (23.5%). Of 17 patients with recurrence, 6
      (35.3%) patients died more than 5 years after operation. The prognosis was poorer
      when the patients were older, and the depth of invasion was greater, lymph node
      metastasis, lymphatic involvement, and vascular involvement were present, and
      lymph node dissection was limited. The independent prognostic factors were lymph
      node metastasis, lymph node dissection, and age by multivariate analysis using
      Cox proportional hazards. Micrometastases within lymph nodes were confirmed in 3
      of 6 node-negative patients with recurrence. CONCLUSIONS: When patients have
      lymph node metastases or are older, close and long-term follow-up and careful
      planning of postoperative adjuvant therapy might be necessary to avoid
      recurrence. The detection of micrometastases by anti-cytokeratin antibody might
      be useful for predicting the possibility of recurrence in early gastric cancer.

PMID- 17523337
TI  - Survival analysis after surgical treatment of gastric cancer: review of 121
      cases.
AB  - BACKGROUND/AIMS: This study was performed to evaluate major morbidity, early
      mortality and to analyze survival in our patients that underwent surgical
      treatment for gastric cancer. METHODOLOGY: Records of 121 patients with gastric
      adenocarcinoma that underwent surgery between 1997 and 2004 were reviewed
      retrospectively. Age, gender, tumor site, presence of local invasion, depth of
      tumor invasion, lymph node metastases, stage of the disease, distant metastases,
      histological differentiation, type of surgery, and blood transfusions were
      evaluated in relation to survival. Survival curves were estimated using the
      Kaplan-Meier method and the differences in survival were compared by the log-rank
      test. RESULTS: Forty-two cases (34.7%) underwent total gastrectomy, 34 (28.1%)
      had subtotal gastrectomy, and 45 (37.2%) received palliative surgery. The
      majority of the patients (61.2%) had stage IV gastric cancer. Total morbidity and
      mortality were 26.4% and 17.3%, respectively. The factors that influence survival
      were type of surgery, adjacent organ invasion, existence of metastases, lymph
      node status, blood transfusions, and stage of the disease in this study. Among
      the significant prognostic factors in the univariate analysis, only one factor,
      R0 resection proved to be independently significant in the multivariate analysis.
      CONCLUSIONS: R0 resection was found to have a significant favorable effect on
      survival in our study.

PMID- 17523338
TI  - Decreasing prevalence of Helicobacter pylori infection: a 9-year observational
      study.
AB  - BACKGROUND/AIMS: Detailed information is still lacking on the trends of changes
      in Helicobacter pylori infection. The aim of the study was to investigate how the
      prevalence of H. pylori infection varied with gender and age during the past 9
      years. METHODOLOGY: A total of 8646 subjects who submitted to a rapid urease test
      were included. The prevalence of H. pylori infection according to age and gender
      was analyzed. RESULTS: H. pylori infection was noted in 3747 cases (43.3%) of all
      cases. The infection rate was 50.0% in 1997, but declined gradually down to 40.6%
      in 2005 (P < 0.001). The rate of H. pylori infection reached a peak at the age of
      30-39 years and decreased thereafter in men while it reached a peak at the age of
      40-49 years in women (P < 0.001). The prevalence was higher in men than in women
      before the age 50 years (P < 0.001) while there was no difference after the age
      50 years (P = 0.28) in any of the years studied. CONCLUSIONS: H. pylori infection
      has gradually decreased over the past decade, and there is a gender-related
      difference in the prevalence of H. pylori infection manifesting as a lower rate
      of infection in young women and an earlier plateau of infection rate in men.

PMID- 17523339
TI  - Metastasis in para-aortic lymph nodes in patients with advanced gastric cancer,
      treated with extended lymphadenectomy.
AB  - BACKGROUND/AIMS: Lymph node dissection is an essential component of curative
      resection for advanced gastric cancer. To improve the survival of N2 patients,
      Asian surgeons have been performing D2+para-aortic lymph node dissection. The
      current study presents the results of lymph node status from multicenter trial of
      D2 and D2 + para-aortic nodal (No.16) dissection (D4 dissection). METHODOLOGY:
      Patients enrolled in the study had potentially curable gastric adenocarcinoma in
      an advanced stage, T2, T3 or T4/N1 or N2. Patients were randomized to undergo
      either D2 or D4 gastrectomy. RESULTS: Two hundred and seventy patients were
      registered and 136 and 134 patients were allocated into the D2 or D4 group,
      respectively. The average nodal yield of No.16 in D4 group was 18.4 +/- 14.1,
      ranging from 2 to 84. No.16 metastasis was detected in 12 (9.0%) of 134 D4
      patients. One, 9 and 2 patients had simultaneous involvement in N1, N2, and N3
      (No.8p, 12, 13 or 14). Namely, in 39 patients who were diagnosed as N2 from the
      lymph node status in N1 and N2 levels, nine (23.0%) patients had No.16
      metastasis. The stage migration by D4 was found in 10 (7.5%). Logistic regression
      analysis revealed that the stations of No.7 and No.8 were the significant
      predictors of No.16 involvement. CONCLUSIONS: The present study may strongly
      suggest that prophylactic D4 dissection may be indicated for patients with N2
      involvement, and that No.7 and No.8 are the junctional nodes for D4 dissection.

PMID- 17523340
TI  - Gastric emptying after pylorus-preserving gastrectomy: assessment using the 13C
      acetic acid breath test.
AB  - BACKGROUND/AIMS: Gastric emptying after PPG is directly associated with
      postoperative QOL. Few studies have investigated gastric emptying after a
      gastrectomy for stomach cancer using carbon-labeled acetic acid breath test.
      METHODOLOGY: We analyzed gastric emptying in 28 patients who underwent a
      gastrectomy for gastric carcinoma. Among the patients, 14 underwent pylorus
      preserving gastrectomy and 14 underwent distal gastrectomy. We recruited 15
      healthy subjects as controls. Gastric emptying was evaluated with the 13C-Acetic
      acid breath test was performed. Postprandial breath samples were collected at a
      15-min interval for 2 hours and at a 30-min interval thereafter. We calculated
      the ratio of (13)CO2 expired per hour and determined the time required to reach
      peak (13)CO2 expiration level. RESULTS: The time required to reach peak (13)C02
      expiration level were 1.78 hours for the patients who underwent pylorus
      preserving gastrectomy, 1.19 hours for the control group and 0.70 hours for the
      patients who underwent distal gastrectomy. CONCLUSIONS: Our 13C-Acetic acid
      breath test following an intake of solid foods showed that gastric retention can
      be preserved after a pylorus-preserving gastrectomy.

PMID- 17523341
TI  - Prevalence of silent gastric ulcer, erosions or severe acute gastritis in
      patients with type 2 diabetes mellitus--a cross-sectional study.
AB  - BACKGROUND/AIMS: Severe gastric inflammation or ulcer disease can alter gastric
      motility and influence sufficient glycemic control in patients with type 2
      diabetes mellitus. However, visceral neuropathy may reduce the perception of
      typical gastrointestinal symptoms in these patients. The aim of the present study
      was to evaluate the prevalence of silent severe acute gastritis, gastric ulcers
      or erosions in asymptomatic patients with diabetes mellitus and to determine
      potential predictive parameters. METHODOLOGY: Seventy-two patients with type 2
      diabetes mellitus and little or no dyspeptic symptoms were investigated by
      endoscopy of the upper gastrointestinal tract under screening conditions. Before
      endoscopy the presence of gastrointestinal symptoms and standard laboratory
      parameters were determined. In addition, the presence of Helicobacter pylori
      infection was investigated by rapid urease test and histology. RESULTS: Highly
      active gastric inflammation was found in 34 patients (gastric ulcers in 10,
      gastric erosions in 21, and histologically acute, grade two or three gastritis in
      3 patients). Episodic heartburn was significantly associated with highly active
      gastric inflammation (odds ratio 2.96 (1.05-8.32), p = 0.036). Elevated levels of
      C-reactive-protein and blood leukocyte counts proved to be of positive predictive
      value for highly active gastric inflammation in patients without other causes of
      acute inflammatory diseases (odds ratio 3.52 (p = 0.026) and 7.64 (p = 0.007)
      respectively). No significant association was found for gender, age, duration of
      disease, BMI, considerably raised HbA1c (>8.5%), complications of diabetic
      disease, general gastrointestinal symptoms, Helicobacter pylori infections and
      therapy with acetylsalicylic acid on 100 mg/d. CONCLUSIONS: The results of this
      study indicate that severe acute gastric inflammation or ulcer disease can occur
      with high prevalence in patients with diabetes mellitus with little or no
      dyspeptic symptoms. Additional endoscopic investigations might be of particular
      diagnostic value in patients with inexplicable raised levels of inflammatory
      parameters like C-reactive-protein or blood leukocyte counts.

PMID- 17523342
TI  - Efficacy of low-dose proton pump inhibitor (PPI) in the eradication of
      Helicobacter pylori following combination PPI/AC therapy in Japan.
AB  - BACKGROUND/AIMS: In Japan, eradication regimens consisting of a proton pump
      inhibitor (PPI) + amoxicillin (AMPC) + clarithromycin (CAM) (PPI/AC) for 1 week
      have been conducted. In the present study, we assessed the eradication rates
      following treatment with low doses of various PPIs. METHODOLOGY: 135 patients
      were divided randomly into one of three 7-day regimens: (i) omeprazole (OPZ) 20
      mg/day + AMPC 1500 mg/day + CAM 600 mg/day (OAC); (ii) lansoprazole (LPZ) 30 mg +
      AMPC 1500 mg/day + CAM 600 mg/day (LAC); and (iii) rabeprazole (RPZ) 10mg/day +
      AMPC 1500 mg/ day + CAM 600 mg/day (RAC). The genetic polymorphism of CYP2C19 was
      also examined. RESULTS: The eradication rates according to the treatment regimen
      were as follows: 69.9% (31/45) for OAC, 62.2% (28/45) for LAC, and 71.1% (32/45)
      for RPZ. No significant differences were found among the regimens. Moreover,
      eradication rates, according to CYP2C19 phenotype (homozygous extensive
      metabolizer (EM), heterozygous EM, and poor metabolizer) were: 68.6% (35/51),
      77.4% (41/53), and 82.4% (14/17), respectively. CONCLUSIONS: In PPI/AC therapy,
      the eradication rate for each low-dose PPI was 60-70%, which is low. Based on
      previous reports, it is considered that doses greater than 40 mg/day OPZ, 60
      mg/day LPZ, and 20 mg/day RPZ are required.

PMID- 17523343
TI  - Laparoscopic gastropexy for chronic gastric volvulus.
AB  - Gastric volvulus is an infrequently encountered clinical entity characterized by
      abnormal rotation of the stomach. Surgical treatment by anterior gastropexy is
      indicated for acute and chronic gastric volvulus. Recently, laparoscopic surgery
      has been used in abdominal surgery. We report the case of a patient with chronic
      gastric volvulus who was treated by laparoscopic gastropexy and evaluated by
      upper gastrointestinal series and endoscopic appearance of the stomach. The
      laparoscopic approach is safe and effective for patients and is considered
      applicable to surgery for other upper gastrointestinal disorders requiring organ
      fixation.

PMID- 17523344
TI  - Cell phones and electromagnetic interference revisited.

PMID- 17523345
TI  - For leaders who care: now is the time to provide patients with the best
      healthcare.

PMID- 17523346
TI  - Developing and leading successful growth strategies.

PMID- 17523347
TI  - Adopting cross-industry best practices for measurable results.

PMID- 17523348
TI  - Narrowing the gender gap in healthcare management.

PMID- 17523349
TI  - Assessing your probability for organizational success: candidates should evaluate
      an organization's culture, values, priorities and practices before accepting.

PMID- 17523350
TI  - Attracting new patients: how CDHPs are creating a better-educated consumer.

PMID- 17523351
TI  - Improving patients' health: Henry Ford's Heart Smart program is making a
      difference.

PMID- 17523352
TI  - Blueprint for Medicare: the march toward a value-based payment program.

PMID- 17523353
TI  - The ABCs of being a mentor: a primer for being both a mentor and a protege.

PMID- 17523354
TI  - Center for Healthcare Governance: effective board development: showing the way
      toward exceptional governance.

PMID- 17523355
TI  - Improving the peer review process: develop a professional review committee for
      better and quicker results.

PMID- 17523356
TI  - Promoting a successful partnership: the Chapters Committee fosters mutual goals
      of ACHE and its chapters.

PMID- 17523357
TI  - From abstract painting to information visualization.

PMID- 17523358
TI  - Introducing 3D cinematography.

PMID- 17523359
TI  - Surface capture for performance-based animation.

PMID- 17523360
TI  - Virtualized reality: perspectives on 4D digitization of dynamic events.

PMID- 17523361
TI  - Multiscaled texture synthesis using multisized pixel neighborhoods.

PMID- 17523362
TI  - Interactive Illustrative rendering on mobile devices.

PMID- 17523363
TI  - Attribute blocks: visualizing multiple continuously defined attributes.

PMID- 17523364
TI  - Seven research challenges of generalized 3D documents.

PMID- 17523365
TI  - How to solve a cubic equation, Part 5: Back to numerics.

PMID- 17523366
TI  - A precomputed approach for real-time haptic interaction with fluids.

PMID- 17523367
TI  - Experienced nurses recommended strategies for retention of nurses in health care
      organizations.

PMID- 17523368
TI  - Ethical issues and new nurses: preventing ethical distress in the work
      environment.
AB  - As new nurses move from the familiar educational milieu into a work situation
      they encounter barriers to caring for patients and their families. The
      characteristics of the contemporary work environment, paired with the
      competencies of the new graduates, have the potential to threaten the ability of
      these nurses to provide safe and effective care for patients thus creating
      ethical distress. Educational interventions in the work place can effectively
      provide adequate solutions to these problems. The keystone between the healthcare
      institution and the development of a competent nurse is an effective mentor. As
      new nurses graduate from school and enter the health care industry they encounter
      many barriers that distract them from caring for their patients. With limited
      experience they are ill equipped to prevent ethical distress when confronted with
      ethical dilemmas. Educational strategies such as an adequate orientation can help
      a new graduate cope with the complexities of a health care industry confronted by
      an increase in acuity of patients, progressively more complex medical
      interventions, and a shortage of nurses.

PMID- 17523369
TI  - Comparison of growth in compensation for hospital administrators and nurses in
      Kansas, 2003 to 2005.
AB  - The current nursing shortage is reaching a critical level (Buerhaus, Donelan,
      Ulrich, Norman, & Dittus, 2006). As baby boomers reach an age when they will
      require increased healthcare the demand for nurses will accelerate over the
      foreseeable future. One issue impacting the desirability of nursing as a career
      is salary compensation. Nurse salaries have not kept up with the rate of
      inflation (American Association of State Colleges and Universities, 2005) while
      hospital Chief Executive Officer (CEO) compensation has increased (Westfall,
      2005). The purpose of this study was to examine the compensation growth of
      hospital CEO's compared to nurses over the past three years in Kansas. Hospital
      CEO data was obtained from the Internal Revenue Service form 990 retrieved from
      the public domain. Nursing salary data was obtained from archival data published
      by the Kansas Department of Labor Statistics. Data analyses described differences
      in the salaries of nurses and chief executive officers in Kansas over a three
      year period and within subgroups defined by geographical region. During this
      three year period Kansas hospital CEOs' compensation increased 23.2% compared to
      a national increase of 9%. Registered Nurses' compensation in Kansas increased
      17.39% compared to a national average of 11%. Licensed Practical Nurse
      compensation in Kansas increased 6.28% compared to a national average of 9%. The
      population in the United States is growing older at the same time demand for
      nurses will accelerate (Lovell, 2006). The shortage of nurses is reaching a
      critical level as hospitals try to provide care. Causes of the shortage are
      multifaceted and include the demand for nurses outpacing supply and compensation
      trends. In Kansas, the supply of nurses is hampered by a present shortage of
      nursing faculty that will be exacerbated by the impending retirement of a sizable
      portion of the faculty in the next decade (Hornberger, Hess, & Thompson, 2005).
      The lack of faculty impairs nursing programs' ability to expand enrollments to
      produce adequate numbers of new nurse graduates (Bliss, Valiga, & Novak, 2004).
      With an insufficient supply of future graduates, hospitals--which employ 60
      percent of all nurses--face the immediate problem of filling enough positions to
      provide adequate care to patients (Cohen, 2006). In spite of this shortage,
      salaries have not risen substantially over the past several years, and real
      wages, when adjusted for inflation, have actually declined (Lovell).

PMID- 17523370
TI  - Kansas nursing occupational outlook 2002-2012.

PMID- 17523371
TI  - Precipitants to psychiatric patient assaults: review of findings, 2004-2006, with
      implications for EMS and other health care providers.
AB  - Violent psychiatric patients present a safety risk for Emergency Medical Services
      (EMS) personnel and other health care providers. Although there have been
      numerous studies of the demographic and clinical characteristics of assaultive
      patients, these studies have yielded limited information in predicting violence.
      Recent research has begun to examine possible specific precipitants to patient
      assaults. This paper reviews the published studies from 2004 to 2006. Psychosis,
      organic impairment, staff interactions, and limit setting were cited as
      frequently occurring precipitants. The implications of these findings and
      specific strategies to reduce these precipitant risks for EMS and other health
      care providers are presented.

PMID- 17523372
TI  - Line-of-duty death: psychological treatment of traumatic bereavement in law
      enforcement.
AB  - A line-of-duty death (LODD) strikingly brings home the risk and vulnerability of
      all law enforcement officers and affects the officer's peers, the entire
      department, the wider police community, and the officer's family. This article
      will place LODD in the context of general bereavement psychology, as well as
      describe some of its unique features. A variety of supportive and
      psychotherapeutic measures will be offered for helping peer and family survivors
      cope with this type of tragedy. This is one important area where police
      psychologists and community mental health clinicians can be of tremendous service
      in applying their specialized training in trauma therapy and grief counseling to
      the special needs of law enforcement and emergency services.

PMID- 17523373
TI  - Associations between major life events, traumatic incidents, and depression among
      Buffalo police officers.
AB  - Police officers are considered to be a highly stressed population due to the
      nature of the work they perform. Repeated exposures to work stress and stressful
      life events can affect one's psychological and physiological well-being. The
      objective of this study was to determine whether negative life events and
      traumatic police incidents are associated with depression in police officers. One
      hundred randomly selected urban officers completed a series of self-report
      measures as part of a cross-sectional pilot study. Using four negative life event
      categories (none, low, medium, and high) a J-shaped pattern was observed with
      mean depression scores (+/- SD) of 9.26 (+/- 7.41), 6.21 (+/- 5.94), 8.17 (+/-
      7.42), and 14.64 (+/- 8.04), respectively (test for linear trend p = 0.0186).
      Adjustment for age (p = 0.0209), then age, gender and ethnicity together (p =
      0.0184) did not alter this pattern appreciably. No association between traumatic
      police incidents and depression was observed. Results indicate that exposure to
      multiple negative life events is significantly associated with elevated
      depression scores among this sample. Police agencies should consider developing
      psychological assistance efforts to help affected officers cope with these events
      and deal with depression.

PMID- 17523374
TI  - Psychological debriefing in cross-cultural contexts: ten implications for
      practice.
AB  - Crisis interventions following exposure to traumatic events have become common in
      most western and in some non-western countries. The literature regarding early
      interventions, specifically the use of Psychological Debriefing (PD), is grounded
      in a western context. Little has been written of its use in different cultural
      settings. This article focuses on the use of PD in different cultural settings,
      as well as some of the conceptual issues related to cross-cultural trauma
      research and practice, which inevitably have implications for the use of early
      intervention. Ten key implications for practice are suggested.

PMID- 17523375
TI  - Saving generalist medicine.

PMID- 17523376
TI  - Medicare and tobacco cessation counseling.

PMID- 17523377
TI  - TransforMED tries to rebuild family medicine.

PMID- 17523378
TI  - Getting beyond blame in your practice.

PMID- 17523379
TI  - Family medicine meets the blogosphere.

PMID- 17523380
TI  - How high-low agreements work in a malpractice case.

PMID- 17523381
TI  - Efficient office design for a successful practice.

PMID- 17523382
TI  - Avoiding ambiguous documentation.

PMID- 17523383
TI  - Allergy diagnostics and the allergist's loneliness.

PMID- 17523384
TI  - Identification of latex UDP glucose pyrophosphorylase (Hev b UDPGP) as a novel
      cause of latex fruit allergy syndrome.
AB  - Based on a recently published unusual ase of food allergy in a latex-allergic
      patients, the present study identifies Hev b UDPGP as a novel allergen in natural
      rubber latex able to cause latex-fruit allergy syndrome and as a novel, potential
      pan-allergen in vegetable foods.

PMID- 17523385
TI  - Comparison of efficacy, safety and immunologic effects of subcutaneous and
      sublingual immunotherapy in birch pollinosis: a randomized study.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) is currently considered a valid
      option to subcutaneous immunotherapy (SCIT), but only a few studies made a direct
      comparison of their effectiveness. The aim of this study was to compare the
      clinical and immunological effects of SCIT and SLIT in pollinosis induced by
      Betulaceae. METHODS: Forty-seven adult patients were randomized to receive SCIT
      or SLIT, performed by Betulaceae (alder, birch, and hazel) extracts from
      Stallergenes (Antony, France) standardized in index of reactivity (IR) with the
      treatment schedules proposed by the producer. The clinical effects were
      established by symptom-medication scores recorded during the month of March. Side
      effects were reported directly by the physicians for SCIT and were registered in
      diary cards by the patients for SLIT. Immunologic evaluation was done by
      measuring specific IgE and IgG4 to Bet v 1. RESULTS: Thirty-four patients (19 for
      SCIT and 15 for SLIT) completed the registration of symptoms and drug consumption
      during pollen period of Betulaceae. Mean cumulative doses of respectively 50.65
      IR by SCIT and 4653.1 IR by SLIT were administered, with a SLIT/SCIT ratio of 92.
      There was no significant difference in mean symptom-medication score between SCIT
      and SLIT. Systemic reactions occurred in 16% of SCIT treated but in none of SLIT
      treated. As to immunologic evaluation, Bet v 1 specific IgE did not rise after
      the pollen season in SCIT treated, while increased non significantly in SLIT
      treated. Bet v 1 specific IgG4 increased in both treatment, buy only the increase
      with SCIT was significant (p = 0.001). CONCLUSION: SLIT and SCIT with a ratio of
      about 100 are equally effective in controlling rhinoconjunctivitis caused by tree
      pollen allergy. SLIT is safer than SCIT, but does not show the same immunologic
      effects on serum specific IgE and lgG4 antibodies.

PMID- 17523386
TI  - Additional benefit of a third year of specific grass pollen allergoid
      immunotherapy in patients with seasonal allergic rhinitis.
AB  - BACKGROUND: Aluminium-adsorbed six grass pollen allergoid therapy for 2 years was
      found to be efficacious and safe in patients with hay fever and seasonal asthma.
      Using high-dose, hypoallergenic allergen products (allergoids) enables a short
      term pre-seasonal treatment regimen. However, it is not known whether further
      treatment beyond 2 yrs had any additional benefit. METHODS: Following an initial
      2-year randomized, double-blind, multi-centre, placebo-controlled clinical trial
      in 154 grass pollen-allergic patients, an additional short course of specific
      immunotherapy with the high-dose, hypoallergenic grass pollen preparation
      Allergovit was performed in 61 patients of the active treatment group during the
      3rd open-label treatment year. RESULTS: Further treatment of patients with the
      Allergovit 6-grass pollen preparation resulted in a further reduction of symptom
      medication score and improved quality of life in comparison to the first and
      second treatment year. Changes in allergen-specific IgG4 levels supported these
      results. CONCLUSIONS: Pre-seasonal short-term immunotherapy with the high-dose,
      hypoallergenic allergen preparation Allergovit has been shown to be efficacious
      and safe. A course of three years of 6-grass pollen SIT further improves allergic
      symptoms, quality of life and reduces the need for anti-allergic medication.

PMID- 17523387
TI  - Alpha-1-antitrypsin deficiency asthma and allergy.
AB  - The biochemistry, genetics and pathology of alpha-1-anti-trypsin deficiency are
      reviewed. The geographical distribution in Europe of more current phenotypes M,
      SZ is discussed. Two cases of alpha-1- anti-trypsin are presented one homozygotic
      ZZ non-smoker without any respiratory pathology and one heterozygotic SZ heavy
      smoker with a severe chronic obstructive pulmonary disease and reversibility to
      Beta-2-mimetics suggesting asthma. The relationship between alpha-1-antitrypsin
      and asthma is discussed and general measures of treatment or prevention
      suggested.

PMID- 17523388
TI  - Chlamydia trachomatis: milestones in clinical and microbiological diagnostics in
      the last hundred years: a review.
AB  - Chlamydia trachomatis an obligate intracellular, Gram-negative bacterium is the
      causative agent of several acute or chronic, local and systemic human diseases
      such as trachoma, oculogenital and neonatal infections. It was discovered in 1907
      by Halberstaedter and von Prowazek who observed it in conjunctival scrapings from
      an experimentally infected orangutan. In the last hundred years the detection and
      study of the intracellular pathogens, including chlamydiae, passed through an
      enormous evolution. This memorial review is dedicated to these important research
      and diagnostic discoveries and to the scientists who significantly contributed to
      this evolution starting from the application of simple light microscopy through
      the cell culture technique, antibiotic susceptibility, antigen and antibody
      detection, serotyping, to the real-time nucleic acid amplification and
      restriction fragment lengths polymorphism analysis. Although the majority of
      these old and new excellent diagnostic methods have been introduced into the
      rutine practice, the trachoma has remained one of the leading causes of
      blindness, and oculogenital chlamydial infections still are the most frequent
      sexually transmitted bacterial diseases, furthermore lymphogranuloma venereum is
      a disease emerging in the developed countries at the beginning of the 21 st
      century.

PMID- 17523389
TI  - Colony morphology mutants of Trichoderma harzianum with increased beta-1,4-N
      acetyl-glucosaminidase production.
AB  - A total of 36 UV-induced mutants with altered colony morphology were isolated
      from strain Trichoderma harzianum T334, a potential biocontrol agent against
      plant pathogenic fungi with the ability to produce constitutively low levels of
      chitinases. The level of constitutive beta-1,4-N-acetyl-glucosaminidase
      production in standing and shaken cultures under non-inductive conditions was
      tested in mutants and compared to that of the parental strain. About 30% of the
      mutants showed significantly increased levels of enzyme production, with strain
      T334 col26a being the best producer. This mutant and the parental strain were
      subjected to in vitro confrontation assays with plant pathogenic Fusarium
      culmorum, Pythium debaryanum and Rhizoctonia solani strains. The mutant
      derivative could be characterized by significantly higher biocontrol index values
      than the parental strain in each experiment, suggesting, that mutants with
      improved constitutive extracellular chitinase secretion could be applied for
      biocontrol purposes against fungal plant pathogens.

PMID- 17523390
TI  - Cell wall ultrastructure of flocculent and non-flocculent Schizosaccharomyces
      pombe strains. Effect of cell wall hydrolysing enzymes on flocculation and cell
      wall ultastructure.
AB  - Scanning and transmission electron microscopic studies revealed the presence of
      slime-like, amorphous material on the surface of Schizosaccahromyces pombe RIVE 4
      2-1 cells, independently, whether they were in flocculated or in non-flocculated
      state. Close contact of the adjacent cells via the merging outermost cell wall
      layers was found, however, only in the case of floc formation, which was induced
      by cultivating the cells in the presence of 6% (v/v) ethanol. Irreversible loss
      of the flocculation ability of the cells by treatment with proteinases suggests
      that proteinaceous cell surface molecules as lectins contribute to the cell-to
      cell interaction during flocculation. Both proteinase K and pronase treatments
      removed a distinct outer layer of the cell wall, which indicated that the protein
      moieties of the phosphogalactomannan outer surface layer has a crucial role in
      the maintenance of cell wall integrity. In the case of lysing enzyme treatment
      the removal of the outermost layer was also observed as the first step of the
      cell wall digestion, while driselase treatment resulted in almost complete
      digestion of the cell wall.

PMID- 17523391
TI  - Characterisation of community structure of bacteria in parallel mesophilic and
      thermophilic pilot scale anaerobe sludge digesters.
AB  - The aim of the present work was to compare the microbial communities of a
      mesophilic and a thermophilic pilot scale anaerobe sludge digester. For studying
      the communities cultivation independent chemotaxonomical methods (RQ and PLFA
      analyses) and T-RFLP were applied. Microbial communities of the mesophilic and
      thermophilic pilot digesters showed considerable differences, both concerning the
      species present, and their abundance. A Methanosarcina sp. dominated the
      thermophilic, while a Methanosaeta sp. the mesophilic digester among Archaea.
      Species diversity of Bacteria was reduced in the thermophilic digester. Based on
      the quinone patterns in both digesters the dominance of sulphate reducing
      respiratory bacteria could be detected. The PLFA profiles of the digester
      communities were similar though in minor components characteristic differences
      were shown. Level of branched chain fatty acids is slightly lower in the
      thermophilic digester that reports less Gram positive bacteria. The relative
      ratio of fatty acids characteristic to Enterobacteriaceae, Bacteroidetes and
      Clostridia shows differences between the two digesters: their importance
      generally decreased under thermophilic conditions. The sulphate reducer marker
      (15:1 and 17:1) fatty acids are present in low quantity in both digesters.

PMID- 17523392
TI  - Subacute sclerosing panencephalitis in Croatia (1994-2004).
AB  - We studied five patients with SSPE during a 10-year period (1994-2004). The first
      clinical symptoms developed at the age of 5-11 years. All patients were
      vaccinated regularly against measles according to the official immunization
      schedule. One patient had measles at the age of 18 months. Two of them had a
      history of morbilliform rash (unrecognized measles) at the age of six and seven
      months, respectively. In two patients, with no history of measles before
      vaccination the disease started after varicella infection. Using complement
      fixation (F) test and EIA, antibodies to measles virus (MV) were detected in the
      CSF and sera of all patients. The CF-antibody titers ranged from 1:1024 to
      1:65536 in sera and from 1:16 to 1:128 in CSF samples. MV antigen was detected in
      brain imprints using IFA in two patients. Electron microscopic analysis revealed
      intranuclear viral inclusions (MV nucleocapsids). Using RT-PCR, viral RNA was
      found in both patients. Nucleotide sequence analysis showed that the viruses
      found in the brain tissue belonged to the wild-type MV D6 genotype [7].

PMID- 17523393
TI  - Elevated serum level of interleukin (IL)-18, interferon (IFN)-gamma and soluble
      Fas in patients with pulmonary complications in tuberculosis.
AB  - Mycobacterium tuberculosis can cause life-threatening complications in which the
      immune response plays an important role. This study was designed to evaluate the
      serum levels of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and soluble
      Fas (sFas) in cases with pulmonary tuberculosis due to confirmed M. tuberculosis
      infection. The study comprised 50 patients with M. tuberculosis classified to 13
      complicated cases and 37 uncomplicated patients. A significant (P<0.05) increase
      was found in the serum levels of IL-18, IFN-gamma and sFas in patients compared
      to controls and also in complicated cases compared to uncomplicated ones.
      Moreover, a positive significant correlation was found between serum levels of
      sFas with IL-18 (r=0.532, P<0.001), and with IFN-gamma (r=0.37, P=0.008) and
      lastly between serum levels of IL-18 with IFN-gamma (r=-0.612, P<0.001). It is
      concluded from these results with the recent observations that IFN-gamma levels
      are elevated after successful MTB treatment, suggest the possibility of enhanced
      Fas expression and then stimulating the infected macrophages to show an increased
      FasL-induced apoptosis. Modulation of FasL system by M. tuberculosis might
      represent an escape mechanism to evade the effect of apoptosis. Moreover, the
      elevated serum levels of IL-18, IFN-gamma and sFas can be considered as
      pathognomonic markers suggesting pulmonary tuberculosis especially in complicated
      cases.

PMID- 17523394
TI  - Bioconversion of benzonitrile to benzoic acid using free and agar entrapped cells
      of Nocardia globerula NHB-2.
AB  - The free and agar immobilized cells of Nocardia globerula NHB-2 having nitrilase
      (EC 3.5.5.1) activity were used to catalyse the transformation of benzonitrile to
      benzoic acid. The whole cells of N. globerula NHB-2 were immobilized in agar
      which exhibited maximum conversion of benzonitrile to benzoic acid in 0.1 M
      potassium phosphate buffer pH 7.5 (free cells) 8.0 (immobilized cells),
      temperature 40 degrees C, cells 2 mg dcm ml(-1) reaction mixture and benzonitrile
      (4% v/v) in 4 h (free cells). The effect of temperature on the stability of
      nitrilase was studied and cells retained 100% activity at 30 degrees C and lost
      50% activity at 40 degrees C. In a fed batch mode of reaction 108 and 84 gl(-1)
      benzoic acid was produced using free and agar entrapped cells (2 g dcm). The agar
      immobilized cells were recycled up to three times and 80, 62, 20 gl(-1) benzoic
      acid was again produced respectively in each of three cycles and a total 244 g
      benzoic acid was produced by recycling the same mass of immobilized biocatalyst.

PMID- 17523395
TI  - [Phosphodiesterase inhibitors in clinical practice. The present and the future.
      Part I].
AB  - Type 5 phosphodiesterase inhibitors (5-PDEI), which have been applied as the
      basic medication for erectile dysfunction, are now being studied in various areas
      of clinical medicine (pulmonology, cardiology, gastroenterology, gynecology etc.)
      This systematic literature review is dedicated to 5-PDEI, the state of the
      problem, the prospects of clinical application of sildenafil, and is based upon
      450 literature sources from MEDLINE database (from 1954 to June 2006) and the
      Cochrane Collaboration database (from 1977 to March 2005) found by key words
      sildenafil, phosphodiesterase, and 5-PDEI. The issues of physiology and
      pathophysiology of 5-PDEI, the historical background of their creation, the
      appropriateness and efficacy of sildenafil in pulmonary arterial hypertension are
      considered in Part I of the review.

PMID- 17523396
TI  - [A study of quality of life of cardiological patients].
AB  - The main methods for evaluation of medical aspects of quality of life (QL) are
      discussed in the article. Special attention is paid to investigation of QL in
      patients with chronic heart diseases. Modern methods of surgical treatment such
      as myocardial revascularization, radiofrequency ablation, and pacemaker
      implantation allow for substantial improvement in QL.

PMID- 17523397
TI  - [Coronary bypass grafting or endovascular angioplasty in patients with coronary
      artery disease with multivascular coronary lesions].
AB  - Myocardial revascularization in a standard method of treatment of patients with
      severe stenocardia and hemodynamically significant lesions of coronary vessels.
      Nowadays, endovascular correction techniques are more and more wide-spread in
      patients with multi-vascular lesions. Earlier comparative studies demonstrated
      absence of differences according to lethal outcome and acute myocardial
      infarction frequencies, but a higher requirement for repeated interventions and a
      higher rate of stenocardia recurrence after endovascular technique application
      vs. surgical treatment. However, nowadays stents with antiproliferative coating
      allowing for significant reduction in restenosis rate are widely used. This
      article is dedicated to analysis of the results of surgical and endovascular
      treatment of patients with multi-vascular coronary lesions.

PMID- 17523398
TI  - [Psycosomatic associations in internal diseases. Part I].
AB  - The author of the review considers associations between such psychological
      factors as anxiety, depression, stress, and personal features, and the most
      common somatic diseases. The paper demonstrates a significant connection between
      anxiety and depression, on the one hand, and the appearance, clinical course, and
      prognosis of a range of diseases, on the other. Evaluation of the appropriateness
      and efficacy of treatment of mental disorders was done on the basis of certain
      randomized studies.

PMID- 17523399
TI  - [Use of allicor to lower the risk of myocardial infarction].
AB  - The aim of the study was to investigate the effects of allicor (a long-action
      garlic-based preparation) on the risk of acute myocardial infarction (MI) and
      sudden death (SD) in patients with coronary artery disease (CAD). Fifty one CAD
      patients were included in this double-blind placebo-controlled study. The
      prognostic risk of MI and SD during ten following years was counted using Cox
      proportional hazards model based on the results of Munster study. Allicor
      administered for 12 months was demonstrated to reduce absolute ten-year risk of
      acute MI and SD 1.5 times in men and 1.3 times in women. The reduction in
      calculated risk parameters was associated with changes in blood plasma lipid
      profile, the most significant of which was reduction in the level of low density
      lipoprotein cholesterol (p < 0.05) by 32.9 mg/dl in men and 27.3 mg/dl in women.
      The results of this study demonstrate that allicor is effective for the reduction
      of multifactor MI and SD risk as a means of secondary CAD prophylaxis.

PMID- 17523400
TI  - [Correction of primary hemostasis in patients suffering from arterial
      hypertension with metabolic syndrome].
AB  - The purpose of the study was to compare the effectiveness of normodipin and
      nebivolol for correction of platelet dysfunction in patients with metabolic
      syndrome. Normodipin was administered to 25 patients during three months in a
      dose of 10 mg a day. Nebivolol was administered to 21 patients in a dose of 5 mg
      a day. The dynamics of anthropometric indices, lipid blood spectrum, lipid
      peroxidation in the plasma and platelets, the antioxidant protection of the
      liquid part of blood and platelets, and aggregative platelet activity were
      evaluated. The results were processed using Student's criteria and system multi
      factor analysis. The use of normodipin effected peroxidation syndrome more
      positively, and optimized platelet function to a greater extent that nebivolol.
      Long-term administration of normodipin is able to stabilize the achieved effect.
      To lower body weight in patients with arterial hypertension with metabolic
      syndrome normodipin application should be combined with non-drug treatment.

PMID- 17523401
TI  - [Cerebral perfusion in patients with arterial hypertension associated with type 2
      diabetes].
AB  - The aim of the study was to assess cerebral perfusion (CP) in patients with
      arterial hypertension in combination with type II diabetes. The subjects were 57
      patients with stage II AH (mean age 51.6 +/- 5.7 years), among who there were 33
      patients without disturbances in carbohydrate exchange and 24 patients with
      compensated or subcompensated type II diabetes. All the patients underwent single
      photon emission computed tomography of the brain with 99m
      Tchexamethylpropyleneamineoxime. The study showed that patients suffering from AH
      with or without type II diabetes had signs of cerebral hypoperfusion and lowered
      cerebrovascular reserve even in the absence of focal neurological symptoms.
      Disturbances in cerebral perfusion were more prominent in patients suffering from
      AH with type II diabetes vs. patients without carbohydrate exchange disorder.

PMID- 17523402
TI  - [Ventilation-perfusion pulmonary scintigraphy for diagnosis of pulmonary
      thromboembolism].
AB  - Ventilation-perfusion pulmonary scintigraphy with analysis ofventilation
      perfusion ratio, apex-base ventilation and perfusion gradient, pulmonary
      perfusion, and the condition of alveolar permeability at the 10th and 30th min
      after inhalation of radiopharmaceutical was carried out in 16 patients with
      clinical and scintigraphic signs of thromboembolism of distal pulmonary artery
      branches and 10 controls. Thromboembolism of distal pulmonary artery branches was
      manifested by an increase in apex-base ventilation and perfusion gradient in both
      involved and intact lungs vs. the same parameters in healthy people. Patients
      with bilateral thromboembolism of distal pulmonary artery branches were
      characterized by an increase in ventilation-perfusion ratio and retardation of
      alveolar permeability.

PMID- 17523403
TI  - [Antihelicobacter effects of melatonin].
AB  - The authors made an attempt to find a new approach to Helicobacter pylori (HP)
      eradication in patients with chronic gastritis and peptic ulcer without
      application of antibiotics, but using melatonin properties instead. The study
      demonstrates an undoubtful effect of melatonin as a preparation that favors HP
      eradication.

PMID- 17523404
TI  - [Gas chromatography for diagnosis and prognosis of destructive pancreatitis].
AB  - One of modern and highly effective methods of diagnostics and differential
      diagnostics of infected pancreonecrosis is chromatographic technique, which
      allows for identification of anaerobic non-clostridial infection in the foci of
      pancreatic destruction by the presence of volatile fatty acids, the specific end
      products of anaerobic bacterial metabolism. Gas chromatography (GC) - mass
      spectrometry (MS) also make it possible to detect in peripheral blood of patients
      with pancreatitis certain metabolites (di-, polyamines, and aromatic amines) that
      are markers of tissue (protein structure) disintegration and the degree of
      pancreonecrosis, which is a valuable indicator of the degree of pancreonecrosis.
      The presence, according to GC - MS analysis, of natural inhibitors of
      transamidinase (compounds of thiourea and its metabolites, the group of
      mercaptopurines and mercapto-derivates of imidazole) in peripheral blood at the
      maximum level--0.71 to 0.78 mmol/l on days 7 to 10 upon the onset of the disease-
      is a prognostically favorable criterion. At the same time, the presence of the
      maximum level of anaerobic non-clostridial infection metabolite in peripheral
      blood 1.12 to 1.31 mmol/l on days 7 to 10 upon the onset of the disease--is
      prognostically infavorable. These chromatographic criteria in combination with
      clinical manifestations can be considered indications to surgical treatment of
      infected pancreonecrosis, and the prognosis of the disease can be based on them.

PMID- 17523405
TI  - [Irritated bowel syndrome: clinico-morphological types].
AB  - One hundred twenty eight patients with irritated bowel syndrome (IBS) were
      included in the study and divided into two equal groups. Group one consisted of
      patients with type II IBS (without atrophic changes in the colon mucosa, CM);
      group II consisted of patients with type II IBS (with atrophic changes in the
      CM); the control group consisted of 24 practically healthy individuals. All the
      subjects, including the healthy ones, were examined using clinical, endoscopic,
      immunohistochemical methods, and electron microscopy. The study found that the
      development of type IIBS was connected with hyperplasia and hyperfunction of
      serotonin-producing cells with intensification of apoptosis. The number of
      colonocytes with nuclei that are immunopositive to D1 cycline increases, and the
      number of colonocyte nuclei that are immunopositive to proliferating cell nuclear
      antigen decreases. The onset of type II IBS is associated with hyperplasia and
      hyperfunction of all apudocyte populations, including those producing melatonin
      and serotonin, and simultaneous reduction of the number and functional exhaustion
      of VIP-producing and mast cells. Colonocyte apoptosis intensifies; their
      proliferative potential decreases.

PMID- 17523406
TI  - [Characteristics of the psychological status of patients with peptic ulcer].
AB  - The article discusses changes in the psychological status and the forming of
      various types of attitude towards the disease in patients with a favorable and
      unfavorable course of peptic ulcer (PU). The subjects of the study were 82
      patients with exacerbation of PU; among them there were 30 patients with a
      favorable and 52 patient with a complicated course. Patients with a favorable
      course of PU did not displayed prominent peaks in SMOL profile, which reflected a
      relatively benign state of their psychological status. Favorable type of response
      to the disease--harmonic and anosognostic--with lesser social disadaptation
      prevailed in these patients. On the contrary, patients with a complicated course
      of PU displayed a relative increase in the profile on the scales, reflecting a
      higher tension in combination with diadaptive response to the disesase, which
      should be taking into account when correcting treatment.

PMID- 17523407
TI  - [Characteristics of a combined course of duodenal ulcer and gastroesophageal
      reflux disease].
AB  - Duodenal ulcer (DU) and gastroesophageal reflux disease (GERD) are often
      combined. A combination of these wide-spread diseases invariantly effects their
      pathogenesis, clinical manifestations, diagnostics, and requires correction of
      methods of their treatment. The authors observed 41 patients suffering from DU
      combined with GERD (main group) and 25 patients with DU alone (control group). A
      higher level of intragastral acidity with cardial "acidification", more prominent
      disturbances in duodenal, gastral and esophageal motor activity leading to
      duodenal spasm, duodenogastral and gastroesophageal reflux (DGR; GER) were found
      in the main group. Heartburn as the main clinical sign of GERD appears, as a
      rule, only in the presence of reflux-esophagitis (RE) confirmed by morphological
      study of bioptats from the lower part of esophagus independently of an endoscopic
      form of GERD, positive or negative. In cases of combined duodenal ulcer and GERD
      certain signs of disturbances in psychoemotional and vegetative spheres were
      revealed, such as hypochondrial changes, moderate changes in cerebral
      hemodynamics (vertebrobasilar basin). Administration of eglonil, an atypical
      neuroleptic with prokinetic activity, as part of complex treatment leads to
      reduction and/or disappearance of heartburn, DGR, GER, morphological signs of RE,
      and improvements in the psychoemotional and vegetative status in patients with
      combined DU and GERD, as well as improvement in quality of life.

PMID- 17523408
TI  - [The characterization of subjects secondarily recognized as disabled due to
      diabetes mellitus (data from the Federal Bureau of Medico-Social Expertise,
      Moscow)].

PMID- 17523409
TI  - [The clinical effectiveness of rabeprazole in patients with acid-related gastric
      and duodenal diseases with various sensitivity of different types of parietal
      gastric cell receptors].
AB  - The authors studied the duration of intragastric acid production at 20 mg of
      pariet in patients with hypergastric gastritis after determination of the
      individual type of parietal gastric cell reception. The study included 40
      patients (12 women and 28 men aged 33.3 +/- 6.7 years). Predominant activity of
      H2 receptors was detected in 32 patients, while M-cholinoreceptor activity
      prevailed in six patients; in two patients receptor type was not defined. Latent
      period (3.1 +/- 0.5 hours), pH(max) (5.4 +/- 0.7), pH24h (3.5 +/- 0.4),
      pH(stimulated24h) (3.0 +/- 0.7) did not depend on the predominant sensitivity of
      either receptor type and was significantly higher in patients taking pariet than
      in patients receiving standard doses of omeprazole (2.2 +/- 0.5 h, 4.0 +/- 0.3,
      2.4 +/- 0.3, and 1.2 +/- 0.3, respectively) or lansoprazole (2.2 +/- 0.6, 4.3 +/-
      0.6, 2.6 +/- 0.3, and 1.3 +/- 0.3, respectively). The clinical effectiveness of
      pariet was evaluated in 20 patients (15 men and 5 women aged 51.6 +/- 5.4) after
      gastric resection, needing antisecretory therapy. Individual reception type was
      studied. The effects of pirenzepine and ranitidine (or famotidine) given in
      standard doses at the beginning of the week were studied in patients with
      predominant H2-hystaminergic, M-cholinergic, or unclear type. After that all
      patients received pariet 20 mg a day. None of the patients displayed predominant
      H2 receptor activity. In 14 patients predominant M-cholinoreceptor activity was
      noted; in six patients receptor type remained unclear. All the patients were
      administered ranitidine (or famotidine) during one week with no clinical effect.
      Six patients with unclear reception type were given gastrozepine for one more
      week, with no effect either. After the beginning of pariet 20 mg a day complaints
      disappeared in all patients within one or two days. The conclusion is that pariet
      in a standard dose possesses higher antisecretory effect vs. other proton pump
      inhibitors, unlike that of H2 histamine blockers, the latter not depending on the
      individual type of gastric parietal cell reception.

PMID- 17523410
TI  - [The influence of socio-economic factors on the compliance of patients with
      treatment of hypertonic disease].
AB  - The authors analyzed 307 questionnaires of patients with essential hypertension
      (EH) in order to study the influence of social and economic factors on compliance
      to outpatient therapy. The analysis shows that about 55% of patients take
      antihypertensive medication on a regular basis. The most frequent reasons for non
      compliance to treatment are financial problems, personal features such as
      forgetfulness and absent-mindedness, lack of motivation towards treatment, the
      necessity to take a large number of drugs, not knowing about the necessity to
      take medicines on a regular basis, fear of complications of the therapy etc.
      There is a strong positive correlation between patients" compliance, on the one
      hand, and the length of the disease and the level of education, on the other. The
      was a negative correlation between compliance, on the one hand, and the number of
      medicines taken, the financial income, the cost of antihypertensive medication,
      and the number of visits to the doctor during the year. Measures to increase the
      compliance of patients with EH to treatment include improvement of education of
      doctors on pharmacoeconomic issues, a wider use of educational actions for
      patients, improvement of the quality of outpatient observation and the work of
      schools for patients with arterial hypertension, as well as introduction of
      preferential provision with pharmaceuticals for all patients with arterial
      hypertension.

PMID- 17523411
TI  - [Long QT syndrome induced by cordaron and quinidine].
AB  - The article presents an observation of a 63-year-old female patient suffering
      from arterial hypertension, coronary artery disease complicated by a persistent
      form of atrial fibrillation during 1.5 months, and hereditary Minkowski-Chauffard
      hemolytic anemia. Treatment with cordaron proved to be ineffective, while oral
      administration of quinidin in a dose of 1 gr (0.2 gr five times a day) led to
      restoration of sinus rhythm. However, long QT interval syndrome complicated by
      ventricular tachycardic paroxysms of torsade de pointes type developed; later it
      transformed into ventricular fibrillation.

PMID- 17523412
TI  - [Secondary leptospirosis].
AB  - The author describes cases of secondary leptospirosis. Secondary infection with
      leptospiras occurred in patients with concomitant pathology. In connection with
      occupational activity or life-style the patients got infected from Rattus
      norvegicus.

PMID- 17523413
TI  - [Are beta-adrenoblockers still drugs of choice for treatment of arterial
      hypertension].

PMID- 17523414
TI  - [Combined action of antibiotics and deoxyribonuclease on bacteria].
AB  - The impact of DNase on formation of biofilms by grampositive and gramnegative
      bacteria was studied. The enzyme was shown to inhibit the biofilm formation and
      have no toxicity to bacteria. When applied to the formed associations, DNase
      potentiated the effect of antibiotics on the bacteria located in them. An
      increase in the antimicrobial effect of various nonrelated antibiotics was not
      connected with a change in the bacteria susceptibility but likely resulted from a
      break of the genetic cooperation of the cells' community, connected with
      functions of extracellular DNA of the biofilm's matrix.

PMID- 17523415
TI  - [Effect of Panavir on influenza A virus reproduction].
AB  - Mitogenic properties of panavir, as well as its effect on the grippe virus
      reproduction in cell systems in vitro and the effect on the survival of mice with
      the experimental grippe infection were studied. It was shown that panavir had no
      cytotoxic action whereas it was characterized by pronounced mitogenic activity
      and subsequently could be considered as a perspective immunomodulator. Under in
      vitro conditions with the use of relatively high doses for the cell contamination
      with the grippe virus, panavir lowered the virus production in the cell systems.
      When the contaminating doses were low, panavir inhibited the virus production
      detected at the early stages of the infection. In the in vivo studies on mice
      with the experimental grippe infection panavir showed antigrippe activity against
      both the romantadine resistant and the remantadine nonresistant populations of
      the grippe A virus.

PMID- 17523416
TI  - [Vancomycin resistant enterococci in etiology of neutropenic enterocolitis:
      prophylaxis, clinical signs and treatment].
AB  - Neutropenic enterocolitis is a severe complication of high dose chemotherapy in
      patients with hematologic tumors. Forty two cases of neutropenia due to intensive
      chemotherapy were analysed. In 6 patients severe enterocolitis with atony and
      hemorrhage and isolation of vancomycin resistant enterococci from the stool
      specimens was recorded.

PMID- 17523417
TI  - [Drug safety: from development to clinical use].

PMID- 17523418
TI  - [New antitubercular antibiotics screening. 2. Characterisation of cell wall in
      Mycobacterium tuberculosos].

PMID- 17523419
TI  - [Levofloxacin and other antibacterial drugs].

PMID- 17523420
TI  - [Biofilm formation by strains of Burkholderia cepacia complex in dependence of
      their phenotypic and genotypic characteristics].
AB  - Biofilm formation was studied in 54 strains of Burkholderia cepacia complex
      isolated in 7 Moscow hospitals. 80% of strains (biofilm groups I and II) had the
      capacity to biofilm formation and only 16.7% of strains (group III) were not
      capable to biofilm formation. Molecular genetic methods allowed to identify one
      of the epidemic markers (CBL, IS hybrid sequence, Burkholderia Cepacia Epidemic
      Strain Marker - BCESM) in 46.7, 23.3, and 33.3% of strains from group I, II, and
      III respectively. Gene cepR from the Quorum Sensing system was identified in
      three biofilm groups in nearly equal frequency (92.3, 96.2 and 100% for group I,
      II, and III respectively), whereas cepl gene was found more often in group I
      (76.9%) and II (65.4%). Strains from all three groups had protease and lipase
      activity and 13.3% of group I strains had chitinolytic activity. B. cepacia
      strains from group I produced hemolysin in 33.3% of cases, from group II--in
      26.6%, and from group III--in 11.1% of cases. The majority of Moscow hospital
      strains of B. cepacia complex were identified as B. cenocepacia (genomovar III,
      group A). RAPD-PCR method enabled to differentiate isolated strains into several
      genotypic variants. 13.3% of strains from group I were susceptible to
      imipenem/ciprofloxacin, as well as 33.3% of isolates from group II and 44.4% of
      isolates from group III.

PMID- 17523421
TI  - [Dry selective culture medium for isolation of streptococci (streptococcal
      broth)].
AB  - Culture medium--dry rich broth for isolation of streptococci--is developed. It is
      characterized by good growth of microorganisms, accumulative effect and prominent
      inhibiting influence on growth of associated microorganisms. During growth of
      streptococci on the medium their main biological characteristic did not change.
      It has been shown that streptococcal broth provided isolation of streptococci in
      pure culture from clinical specimens.

PMID- 17523422
TI  - [Clonal structure of Yersinia pestis populations in experimental soil
      ecosystems].
AB  - Two basic tendencies--formation of latent (uncultivable) form (LF) and hemin
      storage variability--has been revealed during study of clonal structure dynamics
      of Y. pestis populations in artificial soil ecosystems in long-term incubation
      conditions. Y. pestis populations disappeared within 3 - 6 months at 18 - 22
      degrees C, whereas at 4 - 8 degrees C a subsequent replacement of vegetative
      cells on LF, which are capable to prolonged survival (up to 22 months) in soil
      with ability to reversion in the presence of abundance of nutrients, has been
      observed. Bacteria of virulent strain retained all determinants of pathogenicity
      when reverted to LF, whereas bacteria of avirulent strain (defective on plasmid
      of Ca-dependence), on the contrary, undergo further degradation that resulted in
      loss of a pgm locus and gradual disappearance of population. LF revertants of
      highly virulent strain restored properties of initial population and were highly
      virulent.

PMID- 17523423
TI  - [Preventive measure of massive spreading of influenza and acute respiratory viral
      infections].
AB  - Influenza and acute respiratory viral infections (ARVI) continue to be one of the
      most actual medical and social-economic problem. But problem of high incidence of
      ARVI often regarded as problem of influenza only. Information about methods of
      prognosis of massive spreading of ARVI complex and universal system of their
      prophylaxis including influenza is presented in the article.

PMID- 17523424
TI  - [Cholera caused by Vibrio cholerae O1 ctxAB- tcpA+].
AB  - Results of analysis of cholera outbreak during which V. cholerae O1 biovar El-Tor
      ctxAB- tcpA+ was isolated from 2 patients and 30 carriers are presented. Epidemic
      was caused by contamination of water source and water route of transmission.
      Strains identical to ones detected in humans were isolated from water of surface
      well in zone of water intake. Genome and VNTR-analysis of ctxAB- tcpA+ vibrios
      that caused outbreak in Rostov region in 2005 showed that they differed from
      ctxAB- tcpA- and ctxAB- tcpA+ vibrios isolated previously during and beyond of
      outbreaks from patients, carriers and environment and formed separate group with
      certain genotype. These results confirms conclusions of epidemiological analysis
      about imported cause of recent outbreak.

PMID- 17523425
TI  - [Typing of group A streptococci isolated from urban population of different
      social status and age].
AB  - Pulse-electrophoresis, sequencing of emm genes coding protein M and PCR analysis
      of speA, speB, and speC genes were used for characterization of group A
      streptococci (GAS) isolated in different years in Moscow and Tuapse mostly from
      children and military staff. It has been shown that epidemic process of
      streptococcal infection caused by GAS in Moscow is based on circulation of many
      independent clones of Streptococcus pyogenes. Obtained data on complex typing of
      S. pyogenes would be useful for study of molecular epidemiology of diseases
      caused by GAS and improvement of epidemiologic surveillance.

PMID- 17523427
TI  - [Effect of toll-like receptors (TLR) ligands on in vitro synthesis of
      proinflammatory cytokines by peripheral blood mononuclear cells from healthy
      persons and from patients with common variable immunodeficiency].
AB  - Production of citokines of tumor-necrosis factor (TNF)-alpha and interferon (IFN)
      alpha by peripheral blood mononuclear cells (PBMC) from healthy men and from
      patients with common variable immunodeficiency (CVID) after stimulation with
      zymosan, lypopolysaccharides, flagellin and CpG, which are ligands of TLR 2/6,
      TLR 4, TLR 5, TLR 9 respectively, was studied in vitro. In healthy men production
      of TNF-alpha varied between individuals, whereas synthesis of IFN-alpha was
      similar. Spontaneous production of TNF-alpha by PBMC in patients with CVID was
      increased and accompanied by decrease in TNF-alpha production stimulated by each
      analyzed ligands except CpG. Observed changes in TLR-dependent TNF-alpha
      production can play important role in pathogenesis of CVID.

PMID- 17523426
TI  - [Properties of live antibiotics-resistant anthrax vaccine STI-PR after long-term
      storage].
AB  - Study showed that cultural, morphologic, genetic, immunologic characteristics,
      and resistance to antibiotics of STI-PR anthrax vaccine did not change after
      storage during 20 years in lyophilized condition. It has been shown that medium
      for lyophilization plays important role in preservation of vitality of anthrax
      spores. Optimal preservative properties have been observed for thioureal and
      sucrose-gelatinous media for lyophilization. Obtained results give reasons for
      prolongation of shelf live of STI-PR vaccine from 2 - 3 to 5 - 8 years.

PMID- 17523428
TI  - [Alleles distribution of polymorphic promoter region C-590T in interleukin-4
      genes and Q-576r and Ile-50Val regions in IL-4 receptor gene IL-4RA in patients
      with HCV-infection].
AB  - 81 patients with confirmed HCV-infection and 48 healthy volunteers were examined.
      In healthy Caucasian participants living in Siberian region significant
      predominance of C/T genotype in promoter region C-590T of interleukin-4 (IL-4)
      gene and Q/Q and Ile/Val genotypes in points -50 and -576 of IL-4RA gene that
      codes alpha-chains of IL-4 receptor were revealed. In patients with HCV-infection
      predominance of C/T genotype in C-590T region in IL-4 gene (OR = 1.86), R/R
      genotype in Q-576R region of IL-4RA gene (OR=7.86), and Val/Val genotype in point
      Ile-50Val (OR = 2.6) of the same gene. Summary predictive coefficient of
      hepatitis C development in carriers of these genotypes approached to 95%. During
      analysis of role of allelic polymorphism of IL-4 genes in predisposition to
      hepatitis C development it is necessary to consider not only presence of allelic
      variants of promoter regions of the IL-4 genes, but also the polymorphism of
      genes coding molecules binding with this cytokine on target cells membranes and
      in its soluble form.

PMID- 17523429
TI  - [Immunogenicity of surface and capsular antigens of Burkholderia].
AB  - Study showed that five (C3, C6, C9, C10, C11) out of ten chromatographic
      fractions of surface and capsular antigens of B. mallei significantly stimulated
      cell-mediated immunity that manifested in activation of delayed hypersensivity
      reactions (DHS) and phagocyteability of noncapsulated avirulent strain of B.
      mallei with added surface and capsular antigenic complexes. Other fractions did
      not stimulate cell-mediated immunity, furthermore, fraction C8, which contained
      capsular biopolymer with mass of 200 kD (Ar8), was characterized by
      immunosuppressive effect on DHS and phagocytosis. Observed stimulation of cell
      mediated immunity by fractions referred above has been confirmed by assessment of
      their protective effects on the model of experimental melioidosis in white rats.
      Relationship between markers of humoral and cell-mediated immunity, including
      markers of specific response, was not observed.

PMID- 17523430
TI  - [Highly sensitive enzyme-linked assay based on monoclonal antibodies for
      detection of Brucella antigens].
AB  - Mice monoclonal antibodies against lypopolysaccharides (LPS) of Brucella abortus
      has been obtained and characterized. The antibodies detected LPS of B. abortus,
      B. melitensis and B. suis with high sensivity and specificity and did not react
      with LPS of Yersinia enterocolitica O:3, Y. enterocolitica O:9, Salmonella
      typhimurium, and Francisella tularensis. It has been shown that interaction of
      monoclonal antibodies and LPS of Brucella species can be critically dependent
      from buffer system. Obtained monoclonal antibodies allowed to develop highly
      sensitive assay which was able to detect antigens of Brucella species in
      concentrations 0.05 - 0.1 ng/ml. The assay can be used for detection and
      identification of Brucella species.

PMID- 17523431
TI  - [Screening of nonpathogenic strains of Enterococcus faecium with antagonistic
      activity].
AB  - Forty two strains of enterococci were isolated from feces of healthy adolescents.
      Strains were selected according to their antagonistic effects associated with
      bacteriocinogenic and microcinogenic activity. Resistance of enterococci to
      antibiotics, various concentrations of hydrochloric acid and bile, their level of
      production of organic acids and adhesiveness were determined. Characteristics
      related to pathogenicity were investigared in 5 microcinogenic strains of E.
      faecium with broad spectrum of antagonistic activity. Non-pathogenic microcin
      producing strains of E. faecium resistant to physiological concentrations of
      hydrochloric acid and bile with broad spectrum of antagonistic activity against
      obligatory pathogenic and opportunistic microorganisms can be considered as
      possessing probiotic activity.

PMID- 17523432
TI  - [Microbiocenosis of nasal mucous membrane during allergic rhinosinusitis].
AB  - Overall quantity of microorganisms and their relative prevalence on nasal mucous
      membrane in patients with allergic rhinosinusitis are determined. Microbial flora
      in studied group was characterized qualitatively and quantitatively. Obtained
      results showed that there were changes of microbiocenosis of nasal mucous
      membrane during allergic rhinosinusitis and in characteristics of species in
      Staphylococcus genus.

PMID- 17523433
TI  - [Method and equipment for detection of pathogenic microorganisms using tracking
      analytical membranes].
AB  - Method for detection of pathogenic microorganisms in different microbiological
      assays (water, faeces, punctate etc.) has been developed. Device for preparation
      of samples and filtration of studied material through transparent tracking
      membranes with fixed size of pores and subsequent microscopy of filtrate was
      developed also as well as device for filtration of different liquids in closed
      cylinder under pressure. Method significantly increases informativeness and
      reliability of analyses, and decreases of their labor and financial costs.

PMID- 17523434
TI  - [Anti-infectious defense of vagina during use of low-dose monophasic
      contraceptives].
AB  - Increase in incidence of candidal colpitis has been observed during use of
      contraceptive drugs. Elimination of staphylococci from genital tract after use of
      contraceptives was detected in 34,7% of patients. Composition of other aerobic
      microflora did not change. Nonspecific immune reaction was characterized by
      intensified phagocytosis, increase of results of NBT reduction test and level of
      proinflammatory cytokines. Conclusion about inappropriateness of using low-dose
      oral contraceptives in patients with recurrent vulvovaginal candidosis was made.
      Such contraceptives can be recommended to women with prolonged inflammatory
      diseases of reproductive system.

PMID- 17523435
TI  - [Epidemiological characteristic of viral hepatitis C in large industrial city
      settings].
AB  - Prevalence of hepatitis C between different groups of population of Irkutsk is
      described and leading role (73.3%) of injection drug use as a risk factor has
      been shown. It has been established that persons with alcoholism and unemployed
      persons are additional groups of risk of HCV-infection.

PMID- 17523436
TI  - [Anti-rabies immunoglobulin preparation based on F(ab')2 fragments].
AB  - Technology of manufacturing of new anti-rabies immunoglobulin preparation based
      on F(ab')2 fragments has been developed. This preparation is characterized by low
      reactogenicity, increased virus-neutralizing activity and stability.

PMID- 17523437
TI  - [Detection of lipase in Vibrio cholerae serogroup O1 in reaction of volumetric
      agglomeration].
AB  - Study showed that El-Tor strains of V. cholerae isolated from different sources
      produce lipase for hemolysis after cultivation during 24 h on meat-peptone broth
      independently from their toxigenic and hemolytic abilities. Study of 3- and 4
      hours broth cultures of vibrios revealed possibility to differentiate between
      hemolytic nontoxigenic strains and toxigenic nonhemolytic ones. Using antilipaze
      diagnostic kit it was possible to differentiate El-Tor vibrios from vibrios of
      classic biovar basing on lipase production 24 h after cultivation on meat-peptone
      broth that was evident in El-Tor vibrios but not in classic biovar strains.

PMID- 17523438
TI  - [Molecular mechanisms of cytotoxic effect of alpha-toxin of Staphylococcus
      aureus].
AB  - Mechanism of action of Staphylococcus aureus alpha-toxin has been reviewed. Data
      about molecular transformations during cytolytic action, dimensional structure of
      monomeric and oligomeric toxin, its characteristics in different molecular states
      are presented. Data about defects of oligomerization due to modification or site
      induced mutagenesis are discussed.

PMID- 17523439
TI  - [Methods of assessment and control of house dust mites population and mite
      allergen exposure].
AB  - The work is devoted to analysis of various methods of assessment and control of
      house dust mites population and mite allergens in city dwellings using own
      results and the literature data. Data about in-house dust mites biology and
      ecology, mechanisms of their migration and circulation in modern city conditions
      are presented. The comparison of several methods of mites number assessment and
      mite allergens exposure (classical acarological analysis, colorimetric method of
      guanine detection in house dust, immunochemical methods) has been performed and
      their advantages and disadvantages analyzed. As choice of adequate avoidance
      measures is one of the key question, various such measures (mechanical, physical
      and chemical) have been compared.

PMID- 17523440
TI  - [Pathogenicity factors of opportunistic enterobacteria and its role in
      development of diarrhea].
AB  - The data of pathogenicity factors of opportunistic enterobacteria, including
      Klebsiella, Enterobacter, Citrobacter, Proteus, Providencia and Hafnia species
      are submitted. The genetic control and a role of pathogenicity factors of
      opportunistic enterobacteria in development of diarrhea syndrome are presented.
      Data about adhesins, hemolysins, cytotoxic necrotizing factors and bacterial
      modulins are described. The characteristic of cytotonic and cytotoxic
      enterotoxins, including LT, ST, Shiga-like and cytolethal toxins, and mechanisms
      of diarrheagenic action are analysed. The role of bacterial lipopolysaccharide
      (endotoxin) and induction of locally synthesized proinflammatory cytokins in
      pathogenisis of diarrhea are discussed.

PMID- 17523441
TI  - [Effects of antagonists of 1A and 2A/2C subtypes of serotonin receptors on the
      depressive behavior and expression of c-Fos protein in hypothalamus of
      ovariectomized rats].
AB  - We have studied the influence of a chronic administration of the 5-HT(2A/2C)
      receptor antagonist ketanserin (0.1 mg/kg, i.p.) and the 5-HT(1A) receptor
      antagonist NAN-190 (0.1 mg/kg, i.p.) alone or in combinations with 17beta
      estradiol (0.5 mg per animal, i.m.) for 14 days on the depressive behavior and
      expression of c-Fos protein in the paraventricular nucleus of hypothalamus in
      adult ovariectomized (OVX) female rats. The depression in rats was modeled by the
      Porsolt test. The c-Fos protein expression in the paraventricular nucleus of
      hypothalamus was determined using immunohistochemical techniques. In the Porsolt
      test, 17beta-estradiol in OVX rats reduced the immobilization time to some
      extent. Ketanserin alone significantly decreased the immobilization time in OVX
      rats. The chronic administration of ketanserin in combination with 17beta
      estradiol in OVX females potentiated the antidepressant effect of ketanserin. At
      the same time, ketanserin administration led to a significant decrease in the
      level of c-Fos protein in the hypothalamus in OVX rats as compared to the intact
      control. These results are indicative of a substantial interaction between the
      ovarian hormonal system and the serotoninergic brain system involved the
      mechanisms of depression.

PMID- 17523442
TI  - [Manifestations of the antinociceptive and anxiolytic properties of the compound
      GB-115: interactions of cholecystokinin and opioid systems].
AB  - The antinociceptive and anxiolytic properties of the new drug GB-115 (0.0125-4
      mg/kg, i.p.), which is a short peptide antagonist of CCK2-receptors, have been
      studied in rats and mice using thermal models of nociception and the standard
      "elevated plus-maze" (EPM) test for measuring anxiety. It s established that GB
      115 (4 mg/kg) significantly increases the response latency in naloxone
      independent manner in the "hot plate" test in mice and produced a moderate
      naloxone-reversible analgesic effect in the "tail flick" test in mice. The
      blocking of opioid receptors by naloxone does not influence the anxiolytic
      effects of GB-115 (0.025 and 4 mg/kg) in the EPM test on rats. It has been
      suggested that GB-115 produced anxiolytic acting on CCK2-receptors, and its role
      in the control of pain perception is manifested through the interaction with
      opioidergic mechanisms on a spinal level rather than with non-opioid mechanisms
      on a supraspinal level.

PMID- 17523443
TI  - [Discriminative properties of cycloprolylglycine on the operant behavior in
      rats].
AB  - Discriminative stimulus properties of cycloprolylglycine (Cpg) (0.1 mg/kg, i.p.)
      have been studied under liquid-reinforced operant drug-discrimination (Dd)
      paradigm in male outbred rats. It is established that only 33% of rats trained
      under the FRI regime conditions successfully demonstrated Dd "Cpg versus saline".
      After 30 training sessions, a high level of stimulus control was obtained in
      these animals under both non-drug and drug training (appropriate level responses
      were 80% and above). Under more complicated FR10 scheduling during the subsequent
      40 training sessions, the rats failed to demonstrate Dd. Thus, the discriminative
      stimulus properties of Cpg are established, which allows Cpg to be classified as
      pure discriminable substance.

PMID- 17523444
TI  - [Combined action of mexidol and non-narcotic analgesics on pain thresholds and
      emotional stress behavior in animals].
AB  - The influence of non-narcotic analgesics analgin and pentalgin in the basic
      pharmacological effects of diazepam and mexidol has been studied in outbred male
      albino rats. It is established that both analgesics do not influence the activity
      of diazepam. At the same time, they potentiate the analgesic action of mexidol
      without influencing its antistress action and not inducing any side effects. The
      strengthening influence of pentalgin was more pronounced. It is concluded that
      mexidol can be administered in combination with non-narcotic analgesics, in
      particular with pentalgin, for relieving painful syndrome on the background of
      stress.

PMID- 17523445
TI  - [Comparative action of melatonin and bilobil on light perception and
      psychophysiological indices in patients with cerebral trauma anamnesis].
AB  - Pineal hormone melatonin (melaxen preparation) and a typical cognitive enhancer
      Ginkgo biloba (bilobil preparation) decreased the retinal light sensitivity
      thresholds upon two-week administration in young (aged 19-23) patients with
      cerebral trauma anamnesis. This effect was more significant in evening than in
      the morning hours. Both drugs also attenuated the reactive anxiety (bilobil was
      slightly superior to melaxen in this respect) and insignificantly increased the
      volume of acoustic memory. The observed similarity of the psychotropic effect of
      two preparations allows melatonin to be classified into nootropic agents.

PMID- 17523446
TI  - [Comparative evaluation of the neuroprotective activity of phenotropil and
      piracetam in laboratory animals with experimental cerebral ischemia].
AB  - The neuroprotective properties of phenotropil and piracetam were studied in
      Wistar rats with low and high sensitivity with respect to cerebral ischemia
      caused by bilateral irreversible simultaneous occlusion of carotid arteries and
      gravitational overload in craniocaudal vector. In addition, the effects of both
      drugs on microcirculation in the brain cortex under ischemic injury conditions
      were studied. Phenotropil and (to a lower extent) piracetam reduced the extent of
      neuralgic deficiency manifestations, retained the locomotor, research, and memory
      functions in animals with gravitational cerebral ischemia, increased the survival
      of experimental animals, and favored the restoration of local cerebral flow upon
      the occlusion of carotid arteries.

PMID- 17523447
TI  - [Pharmacological properties of phosphorylacetohydrazides in experimental
      myocardial ischemia].
AB  - It is shown that 2-chloroethoxy-para-N-dimethylphosphorylacetohydrazide and N
      acethylhydrazide-para-dimethylaminophenyl-2-chloroethoxyphosphorylacetic acid
      reliably reduce ischemia-induced depression of inotropic functions of the left
      ventricle in cats with experimental myocardial infarction model. The effect of
      both compounds can be explained by the maintenance of viability of the injured
      myocardium via a delay of the development of acidosis and the support of oxygen
      recycling in the ischemized zone. Both compounds show pronounced antiradical
      properties with a non-standard mechanism of action.

PMID- 17523448
TI  - [Features of the pharmacodynamics and pharmacokinetics of furosemide upon long
      term administration in rats].
AB  - Long-term administration of furosemide in rats (single daily dose, 20 mg/kg for 7
      days) was accompanied by a decrease in the diuretic, natriuretic, and kaliuretic
      effects, which was related to a decrease in the rate of renal metabolism and
      excretion. It was found that more than 85% of the daily excretion of sodium takes
      place within the first 6 h after furosemide administration (on the background of
      comparable excretion of the drug), while the elimination of potassium and water
      during one day is more uniform. It is established that the long-term
      administration of furosemide leads to a decrease in the drug excretion during the
      first 6-h period, followed by a growth in the subsequent 18-h period of time.
      These changes in the daily dynamics of drug excretion account for the analogous
      trends in the elimination of water and electrolytes.

PMID- 17523449
TI  - [Effect of dibazol (bendazol) on the generative function in rats].
AB  - The ambiguous influence of bendazol (5 and 160 mg/kg) on the sexual behavior and
      spermatogenesis of rats was observed in experiments on male rats. An increase in
      the duration of sexual activity and a decrease of the total amount of
      spermatozoons were registered irrespective of the course of drug administration
      in a dose of 5 mg/kg. In males treated with bendazol in a dose of 160 mg/kg, the
      behavior varied depending on the duration of treatment: the sexual activity
      decreased upon a 5-day treatment and increased after a 2-month course. The index
      of spermatogenesis did not depend on the time of administration at 5 or 160
      mg/kg, while the spermatozoon mobility was suppressed upon the short-term
      treatment and increased upon the log-term administration of bendazol.

PMID- 17523450
TI  - [Effect on low-molecular-weight heparin obtained using a chitinolytic complex on
      the anticoagulant activity of plasma in rabbits and rats].
AB  - The anticoagulant activity of low-molecular-weight heparin with an average
      molecular weight of 4.7 kD (LMWH-4.7) has been studied. This derivative was
      prepared from unfractionated heparin with the help of chitinolytic enzyme complex
      from Streptomyces kurssanovii. The antithrombin activity of LMWH-4.7 (aIla
      activity) was 72 +/- 9 IU/mg and the activity with respect to the blood
      coagulation factor Xa (aXa activity) was 200 +/- 33 IU/mg, which corresponded to
      an aXa/aIIa ratio of 2.8 (necessary for effective antithrombotic drugs). The aIIa
      and aXa activity exhibited a dose-dependent variation upon intravenous and
      subcutaneous injections in rabbits, so that a high aIIa/aXa ratio was retained: 5
      min after the intravenous injection of a minimum dose (0.3 mg/kg), this ratio was
      2, 7, and for a greater dose (3.0 mg/kg) it reached 3.8. Subcutaneous injections
      were followed by slow elimination of the anticoagulant within 24 h. LMWH-4.7 upon
      intraperitoneal injections produced a dose-dependent inhibition of a model
      thrombosis in rats. Complete inhibition was observed for a dose of 3 mg/kg. Thus,
      it is possible to obtain active LMW heparin with the help of chitinases.

PMID- 17523451
TI  - [Effect of eleutherococcus on hemostasis in immobilized rats].
AB  - The influence of a chronic (30 days) administration of an eleutherococcus extract
      on the haemostatic system state was studied in immobilized rats. A 3-h
      immobilization of untreated animals is accompanied by hypercoagulation and
      thrombinemia signs on the background of downregulation of the anticoagulant and
      fibrinolytic activity, which leads to a risk of thrombosis. Preliminary 30-day
      course of eleutherococcus uptake prevents the immobilization-induced thrombosis
      in rats.

PMID- 17523452
TI  - [Pharmacological correction of lipid metabolism disturbances using new amide
      derivatives of taurine].
AB  - Taurine derivatives taurepar, tauritman and IEM-1702 exhibit a significant
      hypolipidemic activity. The most pronounced effect was observed for taurepar,
      which effectively prevented the experimental dislipoproteinemia in albino rats
      and guinea pigs.

PMID- 17523453
TI  - [Effects of silymarin and its combination with succinic acid on brain
      bioenergetics in rats with experimental inhibition of beta-oxidation of fatty
      acids].
AB  - In the tests on rats with a model of encephalopathy caused by 4-pentenoic acid
      (inhibitor of the beta-oxidation of fatty acids), the hepatoprotective agent
      silymarin increases the respiratory activity in brain mitochondria, improves
      oxidative phosphorylation coupling and energization, and inhibits lipid
      peroxidation. Succinic acid (a regulator of bioenergetics) improves the damaged
      Krebs cycle metabolic pathways and produces an antioxidant effect. The combined
      use of silymarin and succinic demonstrated more expressed cerebroprotective
      action as compared to that of each agent administered separately.

PMID- 17523454
TI  - [Use of acetylcysteine and polyoxydonium for the correction of immune homeostasis
      and antioxidant system impaired by combined action of 1,2-dichloroethane and
      heavy mechanical trauma].
AB  - The experiments on noninbred rats showed that a combination of heavy mechanical
      trauma and 1,2-dichloroethane in a single dose of 0.5 LD50 leads to summation of
      the immunosuppressive and prooxidizing effects of both factors. A combined
      administration of acetylcysteine and polyoxidonium on the background of the
      combined action of a heavy mechanical trauma and 1, 2-dichloroethane (1.5 LD50)
      reduces the suppression of immune responses and the activation of lipid
      peroxidation caused by these factors.

PMID- 17523455
TI  - [Pharmacokinetics of afobazole in rats].
AB  - Afobazole pharmacokinetics was studied after the administration via different
      ways in rats. After oral administration, afobazole is subject to intensive
      biotransformation with the formation of several metabolites (M-6, M-7, and M-11).
      The drug and its metabolites were detected in the blood plasma for 3 h and
      characterized by a high elimination rate after both oral and intravenous
      administration. Afobazole and its main metabolite (M-11) had a medium rate of
      permeability into brain (the target organ): the tissue availability was 0.584 for
      afobazole and 0.793 for M-11. The absolute bioavailability of afobazole upon oral
      administration was 43.6% for. Afobazole was completely absorbed from the
      gastrointestinal tract of rats and characterized by the first-pass effect, after
      which more than 40% of administered dose entered the circulation. The parent
      compound was determined in extremely low amounts in urine and feces: its content
      in 24-h urine on the average did not exceed 0.07% of the administered dose; in 24
      h feces, it did not exceed 0.05 % after intravenous administration and 0.01%
      after oral administration).

PMID- 17523456
TI  - [Effect of losartan on the state of kidney function in rats with experimental
      hyperthyroidism].
AB  - The effect of losartan on the functional state of kidneys was studied in white
      rats with the experimental hyperthyroidism caused by a 5-day oral administration
      exogenous T4 thyroxine in a dose of 50 microg/(100 g body weight). Then, the test
      rats were divided into two groups and animals in the first group received water,
      while animals in the second group were treated with a losartan solution (10 mg/1)
      during 24 hours. Then, the function of kidneys was studied under the condition of
      5% water loading. It was established, that T4 injections resulted in a decrease
      of the clearance of creatinine and an increase in the renal excretion of albumin
      and osmotically active substances. The administration of losartan increased the
      clearance of creatinine and reduced the excretion of albumen via the kidneys. The
      renal effect of losartan is indicative of a reversible character of changes in
      the functional state of kidneys in this stage of experimental pathology.

PMID- 17523457
TI  - [Analysis of passive avoidance learning in a modified three-compartment setup].
AB  - Passive avoidance conditioning is analyzed in a three-compartment apparatus
      comprising the central light compartment, the dark dangerous compartment in which
      the electric foot shock was delivered, and the dark safe compartment where the
      rats were not punished. The passive avoidance performance was characterized, in
      addition to the latent period duration, by the number of visits into the safe
      compartment. The experimental data indicate that the latency of the passive
      avoidance response and the safe compartment preference obey different laws. The
      latency depends linearly on the number of shocks, while neither the safe
      compartment preference nor its relation to the number of shocks was observed.
      Piracetam had no effect on the latency, but enhanced the number of visits into
      the safe compartment. It is concluded that this modified model may be useful in
      an analysis of nootropic effects of neuropsychotropic substances.

PMID- 17523458
TI  - [Neuronal and neurochemical mechanisms underlying the effect of a novel
      antiepileptic drug levetiracetam].
AB  - Published data on the mechanisms involved in the action of levetiracetam (LVT, 2S
      (oxo-1-pyrrolidinyl)butanoic acid amide), a widely used agent for the adjunctive
      therapy of partial epilepsy of different genesis, have been analyzed. A unique
      profile of the anticonvulsant action of LVT was already revealed at the screening
      stage: this agent was not effective in the traditional tests, but it demonstrated
      a pronounced protective effect in kindling models and in the experiments on mice
      sensitive to the audiogenic convulsions. Now it is commonly accepted that the LVT
      mode of action is different from that of the other known antiepileptic drugs. LVT
      was shown to have specific binding sites in the brain. It is believed that the
      synaptic vesicle protein SV2A is the binding site for LVT, and the main mechanism
      of its action involves the modulation of this protein functions, which probably
      accounts for the unique profile of the antiepileptic activity of LVT. The results
      of investigations of the neurochemical mechanisms of LVT action suggest that
      proteins involved in the vesicular exocytosis, in particular SV2, can be
      promising targets in the search for new effective agents for the treatment of CNS
      diseases.

PMID- 17523459
TI  - [Depression as a side effect of alpha-interferon: mechanisms of development and
      criteria for experimental evaluation].
AB  - Possible mechanisms of the development of depression as a side effect of the a
      interferon are reviewed. Methods used for the characterization of depressive
      states in experiment are considered.

PMID- 17523460
TI  - [Asymmetry of the bioelectrical activity of the human brain at different levels
      of consciousness].
AB  - Asymmetry of different human EEG indices was studied at different levels of
      consciousness. Subjects' self-reported changes in the content of consciousness:
      the intensity and quality of involuntary mental processes served as indicator of
      the level of consciousness. It was shown that a certain profile of EEG asymmetry
      corresponded to each the observed level of consciousness. In active state of
      consciousness, the connections in the high-frequency bands: beta-2 and gamma,
      were more pronounced in the left hemisphere of the brain. At the same time,
      transition of the focus of coherent connections to the right hemisphere was
      characteristic of the state of inhibition of "internal speech". The
      interhemisphere dynamics of autospectra amplitude and foci of coherent
      connections supports the notion that the character of interhemisphere asymmetry
      of the brain bioelectrical activity depends on its functional state.

PMID- 17523461
TI  - [Impulse activity in the CA1 field in animals of various typological groups
      exposed to emotional stimuli].
AB  - Hippocampal unit activity in the right and left CA1 fields was studied in rats
      divided in two groups by the method of "emotional resonance": the animals that
      did (A) and did not stop (E) crying of rat-partner. The rate of neuron firing was
      studied in the state of hunger, satiation, and under exposure to intracranial
      electrical stimulation of the emotional positive and negative structures of the
      brain. It was shown that the intracranial stimulation, especially positive,
      increased the rate of firing. Under exposure to emotional stimuli, the neural
      activity was asymmetric only in the A rats. The activity at the left was more
      intensive than the right-sided activity and did not depend on the sigh of
      emotion.

PMID- 17523462
TI  - [Integral mechanisms of regulation of oxygen delivery and consumption in human
      body].
AB  - With new algorithms of pattern recognition three types of regulation of oxygen
      delivery and consumption were studied: at normal regulation, hypo- and
      hyperfunction of heart. It is shown that a surplus systemic blood flow results in
      increase of arterio-venous shunt flow. Insufficient blood flow results in
      increase of arterio-venous gradient of blood oxygen content due to the increase
      of gradient of oxygen content on both sides of capillary wall and to activating
      of vasomotor function of microcirculatory arterial bed. Quantitative estimations
      of shunt and capillary blood flow are obtained.

PMID- 17523463
TI  - [Role of kappa-opioid receptors in the regulation of cardiac resistance to
      arrhythmogenic effects of ischemia and reperfusion].
AB  - It was found that pretreatment of rats with selective agonist of kappa1-opioid
      receptors (OR) (-)--U--50.488 decreased the incidence of ischemic (10 min) and
      reperfusion (10 min) ventricular arrhythmias. The selective kappa2-OR agonist GR
      89696 had no effect on the incidence of ventricular arrhythmias during a 10-min
      coronary artery occlusion and following reperfusion in anesthetized rats. The
      effect of (-)--U-50.488 was abolished by the selective kappa1-OR antagonist of
      non-binaltorphimine and the non-selective peripheral OR antagonist naloxone
      methiodide. Perfusion of isolated rat heart with (-)--U-50.488 did not affect
      arrhythmias during ischemia and reperfusion. The authors suggest that stimulation
      of kappa1-opioid receptors located outside the central nervous system increases
      heart resistance against arrhythmogenic action of ischemia/reperfusion,
      antiarrhythmic action of (-)--U-50.488 being mediated through extracardiac opioid
      receptors.

PMID- 17523464
TI  - [Study of endothelium-dependent blood oscillations in the human skin
      microcirculatory bed].
AB  - Cutaneous microcirculation parameters were studied with laser Doppler flowmetry
      in healthy volunteers. To investigate endothelial-dependent peripheral blood flow
      oscillations the iontophoresis of 1% acetylcholine solution was carried out. To
      estimate the contribution of rhythmical components in blood flow signal the
      continuous wavelet-transform spectral analysis was used. To reveal correlation
      between microcirculation parameters under study the correlation analysis was
      used. The microcirculation index was shown to be the factor producing cross
      correlation dependences. The only positive significant correlation between the
      blood flow oscillation amplitude in the range of endothelial activity normalized
      to mean microcirculation index at rest and maximal microcirculation index during
      the iontophoresis of acetylcholine was revealed.

PMID- 17523465
TI  - [Cardioelectric field on the atrial surface in pigs].
AB  - The form and distribution of extracellular cardioelectric potentials and the
      sequence of the excitation wave propagation on epicardium of the pig atria were
      studied by the method of multichannel synchronous cardioelectrotopography. The
      studies have shown that in pig the excitation wave breaks on epicardium of the
      right atrium at the base of the upper vena cava. Negative initial atrial
      complexes are registered in this area. Two fronts of excitation wave spread from
      the zone of initial epicardial activation: one--to upper segments of dorsal and
      ventral sides of the right atrium, the second--to inter-atrial septum. The
      excitation wave comes to the left atrium with a delay relative to the beginning
      of depolarization of the right atrium. On account of the successive movement of
      the front of the excitation wave from pacemaker the two-phase potentials are
      formed on greater part of the epicardium of the pig atria. The lower part of the
      auricle of the left atrium is depolarized in atrial epicardium in the last turn.
      The sequence of excitation wave propagation in atrial epicardium close to
      ravenous (dog) and ungulate (sheep) animals and man is typical for the pig, but
      herewith the differences in time of covering the atria with excitation do exist.

PMID- 17523466
TI  - [Adaptation to short-term stress exposure increases the activity ATP-sensitive
      potassium channels in the smooth muscle cells of coronary blood vessels].
AB  - The study was aimed at the effect of prior adaptation to short-term stress
      exposure on changes in K(ATP)-channel activity induced by severe stress and the
      dependence of the changes on the state of endothelium which plays important role
      in autoregulation of the coronary flow and myocardial contractility. Experiments
      were conducted on isolation hearts of female rats. At the first step of
      experiment, the heart was perfused by Krebs-Henseleit solution; at the second
      step, the heart was perfused with the same solution in which glibenclamide (1
      microM), glibenclamide with saponin or N(omega)-nitro-L-arginine (60 microM)
      methyl ether was added. During the experiment, the perfusion pressure was
      stepwise elevated from 40 to 120 mm Hg with 20 mm intervals (coronary
      autoregulation). Adaptation to short-term stress prevented development of stress
      specific myocardial hyperperfusion (increased volumetric velocity of coronary
      flow against the background of decreased myocardial contractility) and the
      reduction of coronary dilation reserve. In coronary vessels of adapted rats, as
      distinct from control rats, basal glibenclamide-sensitive functional activity of
      K(ATP)-channels depended on presence and functional activity of endotheliocytes;
      it was reduced in presence of endothelium and increased after de-endothelization
      or NO synthase inhibition. In all experimental groups, the increase in
      glibenclamide-sensitive functional activity of K(ATP)-channels induced by NO
      synthase inhibition more than twice as great as after the endothelium denudation.
      In adapted animals, stress did not decrease the functional activity of K(ATP)
      channels and their activity slightly depended on presence of endotheliocytes. In
      addition, the elevation of their functional activity characteristic of adaptation
      and evident after endothelium removal has vanished. Therefore adaptation to short
      term stress exposure is associated with a potential increase in basal activity of
      K(ATP)-channels which enhances the potency of vascular dilation system and may
      apparently reduce the risk of high vascular tone when such important local
      regulatory system as the NO system is damaged.

PMID- 17523467
TI  - [Effects of marinobufagenin on electrophysiological and contractile
      characteristics of the rat diaphragm].
AB  - Effects of Na+,K(+)-ATPase inhibitor: marinobufagenin, on contractile and
      electric characteristics of isolated rat diaphragm were studied for the first
      time. Marinobufagenin induced dose-dependent (EC50 = 0.3 +/- 0.1 nM) increase in
      the contraction force (positive inotropic effect). At 1-2 nM, it slowed down the
      fatigue induced by continuous direct stimulation (2/s) of the muscle.
      Marinobufagenin at the same concentrations did not affect resting membrane
      potential or parameters of action potentials of muscle fibers, while at 10 and 20
      nM it induced hyperpolarization by approximately 2 mV. Marinobufagenin blocked
      dose-dependently (IC50 = 2.9 +/- 2.0 nM) hyperpolarizing effect of acetylcholine
      (100 nM) mediated by increase in electrogenic contribution of alpha2 isoform of
      the Na+,K(+)-ATPase. This result suggests a capability of marinobufagenin to
      inhibit this isoform of the Na+,K(+)-ATPase. Possible mechanisms of
      marinobufagenin effects in skeletal muscle are discussed.

PMID- 17523468
TI  - [Diagnosis of early disorders of the orthostatic regulation by the
      bioimpedancemetry technique].
AB  - By programmed machine ABC-01 ("Medass" company, Moscow) was performed evaluation
      of the impedance dynamics in various parts of the body and the diagnostic
      opportunity this system at 40 health man. Donosologic impairment oforthostatic
      regulation was discovered at the 13 participations.

PMID- 17523469
TI  - [The effects of desensitization of capsaicin-sensitive neurons on the blood flow
      in microvessels of the rat gastric serous muscular membrane with normal and
      insufficient contents of glucocorticoids].
AB  - The effects of desensitization of capsaicin-sensitive neurons on the blood flow
      velocity in microvessels of the gastric muscular membrane were investigated
      before and after indomethacin (35 mg/kg) administration in adrenalectomized rats
      with or without corticosterone replacement (4 mg/kg sc) and in sham-operated
      animals. Desensitization of capsaicin-sensitive neurons was performed with
      neurotoxic dose of capsaicin (20 + 30 + 50 mg/kg sc) two weeks before the
      experiment. Adrenalectomy was created one week before the experiment. The in vivo
      microscopy technique for direct visualization of gastric microcirculation and
      analysis of red blood cell (RBC) velocity was employed. Indomethacin decreased
      the RBC velocity. Adrenalectomy by itself profoundly decreased the RBC velocity,
      whereas corticosterone replacement prevented this effect. Desensitization of
      capsaicin-sensitive neurons did not influence the RBC velocity in sham
      adrenalectomized rats; however, it induced further fall of both basal and
      indomethacin-induced RBC velocity in adrenalectomized rats that was prevented by
      corticosterone. We conclude that glucocorticoid hormones have a beneficial effect
      on the blood flow velocity in microvessels of the gastric muscular membrane in
      rats with desensitization of capsaicin-sensitive neurons.

PMID- 17523470
TI  - [Properties of lung surfactant during changes in capsaicin-sensitive vagal
      afferents under conditions of emotional stress].
AB  - In this work, we investigated surface active properties and biochemical
      composition of pulmonary surfactant under emotional stress in condition of
      neuropeptides pool exhaustion in capsaicin-sensitive afferents of the vagus
      nerve. It is shown that stress is accompanied by decrease of lung surface active
      properties and increase of total phospholipids content as result of
      phosphatidylcholine and lysophospholipid fraction rise. After capsaicin
      application on the cervical part of the right vagus nerve stress-induced
      alterations in ipsilateral lung become less considerable, whereas all spectra of
      changes in contralateral lung is remained.

PMID- 17523471
TI  - [Genetic markers of pathogenicity of conditionally pathogenic enterobacteria
      isolated from children with diarrheal diseases].
AB  - In the process of examination of 89 children from different age groups with
      diarrheal disease caused by bacteria from Enterobacteriaceae family 89
      microorganisms were isolated including Klebsiella spp. (37 isolates), Citrobacter
      spp. (9 isolates), Enterobacter spp. (17 isolates), Hafnia alvei (1 isolate),
      Morganella morganii (11 isolates), Proteus spp. (14 isolates). Presence of genes
      associated with pathogenicity islands (PAIS): hlyA, hlyB (hemolysin), sfaG
      (fimbria antigen type S), cnf1 (cytotoxic necrotizing factor 1), estB (heat
      stable enterotoxin B)were studied in these cultures by PCR. It was found that
      32.6% of examined isolates had fragments of PAIS's genes--hlyA was detected in 9
      cases (10.1%), hlyB--in 10 cases (11.2%), sfaG --in 8 cases (9%), cnf1--in 9
      cases (10.1%), and estB--in 3 cases (3.4%). Positive correlation between genetic
      determinants hlyB and cnf1 as well as hlyA and sfaG was found while estB was not
      associated with other genes. Weak positive correlation between presence of sfaG
      and resistance to tetracycline and chloramphenicol was detected. Factors coded by
      revealed determinants of PAIS can play a role in the development of diarrheal
      syndrome.

PMID- 17523472
TI  - [Animals in a city: unrecognized biological threat].
AB  - Problems related to risk of contracting of zoonotic infections and invasions by
      people in a city has been discussed. Such risk is related with wide-accepted
      practice to keep pets and wild animals in city flats and absence of knowledge in
      general population about animals' parasites and measures of individual
      prophylaxis of zoonosis. Large number of stray dogs and habitation of wild animal
      species on territories of cities represent additional threats. Conclusion about
      need of inclusion of prophylactic and antiepidemic measures in programs of city
      improvement was made.

PMID- 17523473
TI  - [Mathematical modeling and prognosis of incidence of enteric anthroponoses with
      aqueous route of transmission].
AB  - Using data on long-term dynamics of epidemic process of acute enteric infections
      enteric with aqueous route of transmission (typhoid fever, shigellosis caused by
      Shigella flexneri, hepatitis A, rotavirus gastroenteritis, etc.)the equation of
      regression was developed with the help of Chebyshev's polynoms. Predicted
      incidences of these infections for 2005 were on 61.2-99.5% in agree with the real
      ones on two territories of north region of West Siberia. Predicted incidence for
      2006 is reflecting tendencies of epidemic process of mentioned infections.

PMID- 17523474
TI  - [The molecular epidemiological aspects of hiv-infection spreading in Perm
      region].
AB  - Retrospective analysis of HIV-infection spreading in Perm region in conjunction
      with the genetic characterization of viral subtypes circulated on this territory
      from 1988 (when 1st case of infection was detected) until 2005 was performed.
      Analysis of epidemic process allowed to determine three periods of its
      development basing on both epidemic intensity and nature of circulating HIV-1
      subtypes. During 1988 - 1996 (first period), when viral population was
      heterogenous (simultaneous circulation of three HIV-1 subtypes) with multiple
      routes of transmission, the epidemic process was characterized by low intensity.
      High incidence of HIV-infection among injection drug users and high homogeneity
      of circulated HIV-1 variants (98% of isolated variants belonged to HIV-1 subtype
      A with low level of genetic variability) were characteristics of the second
      period lasted from 1997 to 2001. Decrease in HIV-infection incidence in 2002-2005
      was accompanied by the increase of HIV-1 transmission through heterosexual
      contacts and continuation of subtype A predominance between isolates. However
      increase in heterogeneity of viral population during this period, which
      manifested as increase of env and pol genes polymorphism, was detected.

PMID- 17523475
TI  - [Surveillance of acute flaccid paralysis in Belarus].
AB  - The ten-years experience of acute flaccid paralysis (AFP) surveillance in Belarus
      has been summarized. Among 456 AFP cases reported from 1996 to 2005, 11 were
      classified as vaccine-associated paralytic poliomyelitis (VAPP), 445--as non
      polio AFP. The risk of VAPP for the period 1996-2001 was 1 case per 745,000 used
      doses of oral poliovaccine (OPV). For the recipients of OPV the risk was 1 case
      per 911,700 doses and for the first-dose recipients--1 case per 96,000 doses. The
      high incidence of VAPP was a reason for implementation of sequential polio
      vaccination schedule in 2000. Guillain-Barre syndrome dominated among non-polio
      AFP (39.3% of cases); more rare were traumatic neuritis (27.9% of cases),
      transient monoparalysis (12.1%), myelitis (7.6%). Non-polio AFP differed from
      VAPP by following epidemiological and virological characteristics: predominance
      of previously repeatedly vaccinated against poliomyelitis; development of
      paralysis in long-term period after vaccination; isolation of non-polio viruses
      belonged to three serotypes of Coxsackie B viruses (B1, B4, B6) and six serotypes
      of Echo viruses (6, 7, 11, 14, 24, 25) in 8.1% of cases; absence of typical for
      polio residual paralyses in patients who excreted vaccine polioviruses.

PMID- 17523476
TI  - [Immunogenicity of modified by dextran recombinant fragment of Bac protein of
      group B streptococci].
AB  - Opportunity to increase of immunogenicity of recombinant polypeptide P6
      constructed on the basis of surface protective Bac protein by its chemical
      conjugation with dextran (D) 40 was studied. 3 preparations with different
      quantity of protein and polysaccharide components were obtained. Their testing
      with standard serum showed that antigenic determinants of the polypeptide were
      preserved although partly enclosed and structure of antigenic determinants did
      not significantly changed. On the model of subcutaneous immunization of mice it
      has been shown that two preparations--P6D2 and P6D3--have improved immunological
      characteristics. Conjugation of polypeptide P6 with dextran let to increase of
      immune response to P6 and affinity of P6-specific antibodies. Injection of
      nonconjugated P6 and dextran mixture showed that free dextran is not immunogenic
      and it suppress synthesis of P6-specific antibodies without effect on their
      affinity. Intranasal administration of nonconjugated P6 did not lead to P6
      specific IgG in serum. After conjugation with dextran polypeptide P6 was
      recognized as an antigen and stimulated production of small quantity of
      antibodies. Technological process of chemical binding of protein antigen with
      polysaccharides, which let to regulate protein and polysaccharide components
      ratio, can be the effective method to increase immunogenicity of recombinant
      polypeptides.

PMID- 17523477
TI  - [Experimental evaluation of the brucellosis therapeutic vaccine efficacy].
AB  - Use of antibiotics can't completely solve the problem of brucellosis treatment,
      especially its chronic forms, because antibacterial preparations do not eliminate
      main pathogenetic factor of the disease--sensibilization of the macroorganism. It
      makes actual the question about complex immuno- and antibacterial therapy. Long
      term clinical experience proved high effectiveness of a therapeutic brucellosis
      vaccine. Earlier this preparation was manufactured in Research Institute of
      Vaccines and Sera in Tbilisi (Georgia). To date new composition of components of
      the vaccine has been developed, and manufacturing and control methods have been
      improved. Marked desensitizing effect of the vaccine and its stimulatory action
      on cellular and humoral immunity has been observed. In 2002 technological
      normative documentation for manufacturing and use of the vaccine was developed in
      the Research Institute of Microbiology (Kirov) and production of the vaccine
      began.

PMID- 17523478
TI  - [Clinical and immunological characteristics of rubella in western Siberia].
AB  - Evaluations of immune system of 155 patients with rubella and 90 contacts with
      patients were examined. Detection of viral genetic material in blood, urine, and
      nasopharyngeal swabs has been performed using RT-PCR method. Clinical diagnosis
      has been confirmed by RT-PCR in 114 (73.5%) patients. Changes of laboratory tests
      for rubella without clinical signs of the infection were observed in 20% of
      contacts. Complex ELISA- and PCR-assisted examination of patients can help to
      determine the stage of disease and characteristics of immune response. For
      differential diagnostic of rubella and other infectious diseases with exanthema
      it is rational to perform complex examination of patients using immunologic and
      molecular biologic methods.

PMID- 17523479
TI  - [Adequate selection of antigens for serologic diagnostics of experimental
      melioidosis].
AB  - Sera of Burkholderia pseudomallei-infected golden hamsters, white mice, guinea
      pigs and white rats were studied. Immunochemical analysis revealed presence of
      antibodies against antigens 2, 3, 6, d, and g with significant predominance of
      antibodies to antigens 6 and d. Antigen d was detected irrespectively to strain
      used for experimental infection and experimental animal species. Antibodies to
      antigen 6 were detected only when strains belonging to Asian serovar, but not to
      Australian serovar, were used. On the basis of antigens 6 and d following methods
      of serologic diagnostics were developed: reaction of indirect hemagglutination,
      reaction of latex agglutination, and radioimmunological assay. Their sensitivity
      and specificity reached 100% during experimental melioidosis in golden hamsters,
      guinea pigs and white rats.

PMID- 17523480
TI  - [Assessment of bactericidal and growth-inhibiting activity of blood serum using
      flow cytometry and photometry].
AB  - Method of measurement of biological fluids bactericidal activity against
      Staphylococcus aureus using laser flow cytometry has been developed and proposed
      for clinical use. Overall bactericidal activity of sera of healthy donors has
      been assessed by this method. Strong positive correlation between bactericidal
      activity measured by flow cytometry and ability of the sera of healthy donors to
      inhibit bacterial growth assessed by photometric method was determined. High
      degree of positive correlation between results of cytometry and classical
      microbiological method of measurement of mentioned parameters has been shown.

PMID- 17523481
TI  - [Effect of carrageenan on non-specific resistance to LPS-induced endotoxemia in
      mice].
AB  - The study showed that kappa/lamda-carrageenan increase non-specific resistance to
      impact of Escherichia coli lypopolysaccharide (LPS)-induced endotoxinemia in
      mice. Carrageenan was administered intragastrically in dose 100 mg/kg/day during
      5 days followed by intraperitoneal injection of LPS in dose 1 mg/kg. Carrageenan
      hampered the involution of thymus, hypertrophy of adrenal glands, the changes on
      level of thyroid hormones and corticosterone in serum, the activation of
      glycogenolysis, glycolysis, and peroxidation of lipids in liver.

PMID- 17523482
TI  - [Impact of bacterial lectin on functional activity of lymphocytes].
AB  - Impact of Azospirillum brasilense Sp7 lectin with carbohydrate specificity to L
      fucose on T- and B-lymphocytes production, activity of IL-1alpha, and TNF-alpha
      was studied in vitro and compared with influence of red kidney bean
      phytohemagglutinin (PHA) on the same parameters. Increase of growth of T- and B
      cells subpopulations has been shown that point to stimulatory effect of the
      bacterial lectin. Bacterial lectin of A. brasilense also increased synthesis of
      IL-1alpha and TNF-alpha. It has been shown that the bacterial lectin has more
      pronounced stimulatory effect on functional activity of lymphocytes compared with
      PHA.

PMID- 17523483
TI  - [Microbiologicaland immunological criteria for estimation of ureaplasmosis
      treatment efficacy in women].
AB  - The role of surface and parietal vaginal microbiocenosis and immunoglobulins in
      development of infectious process, in prediction of resistance of causative
      microorganism to antibiotics and treatment efficacy was demonstrated on group of
      women with ureaplasmosis. Evaluation of anaerobic part of vaginal microbiota
      contemporary with its aerobic part reliably increased informative value of
      microbiological test in women with urogenital diseases. There are reasons to
      include interferon preparations into the complex therapy of ureaplasmosis.

PMID- 17523484
TI  - [Microbiocenosis of stomach in children with chronic gastritis].
AB  - Qualitative and quantitative composition of gastric microflora has been studied
      in 30 children with chronic gastritis. Bacteriological study of gastric biopsies
      and parietal mucus in 10 children with chronic gastritis not associated with
      Helicobacter pylori more frequently revealed conditionally pathogenic bacteria-
      Escherichia coli, Staphylococcus aureus, Streptococcus viridans, S. pyogenes
      (group A), Peptostreptococcus anaerobius, P. prevotii and their associations. In
      20 studied patients with H.pylori-associated chronic gastritis composition of
      local microflora was less diverse--conditionally pathogenic, lacto- and
      bifidobacteria often were absent. Study showed that eradication of H. pylori led
      to appearance of conditionally pathogenic bacteria in stomach microflora, which
      were frequently isolated in associations. Not effective treatment was associated
      with disappearance of lacto- and bifidobacteria and frequent isolation of Candida
      albicans.

PMID- 17523485
TI  - [Bacillus subtilis metabolites as a novel promising probiotic preparations].
AB  - Characteristics of Bacillus subtilis metabolites contained in supernatants of its
      broth cultures are described. Metabolites contained bacterium-produced
      biologically active components ensuring cells growth and propagation. These
      components had bacteriostatic and bactericidal effect on gram-positive and gram
      negative pathogenic and conditionally pathogenic microflora of gastrointestinal
      tract of human and animals. Enzymes produced by the bacterium (amylase, protease,
      cellulose-decomposing enzyme, lipase, pectinase) increased antagonistic
      properties of preparation and promote its probiotic effect.

PMID- 17523486
TI  - [Level of lactoferrin in serum and cerebrospinal fluid of patients with
      meningitis].
AB  - Study showed 9-fold increase of concentration of lactoferrin (LF) in serum of
      patients with bacterial meningitis (BM) compared with normal concentration and 5
      fold increase of LF concentration in patients with aseptic meningitis (AM). Level
      of LF in cerebrospinal fluid (CSF) of patients with BM and AM was 200-fold and 22
      fold higher than in control group respectively. In 71% of patients with AM
      concentration of protein in CSF did not exceed minimal level observed in patients
      with BM. Level of LF in serum and CSF during treatment statistically
      significantly decreased. Concentration of LF (the latter is marker of
      neutrophilic granulocytes activation) can be used as a characteristic of
      acuteness and intensity of inflammatory process in central nervous system,
      whereas detection of LF in CSF--as additional criterion in differential
      diagnostics between bacterial and viral meningitis. Furthermore, repeated
      measurement of LF level can be useful for monitoring of disease course and
      assessment of effect of treatment.

PMID- 17523487
TI  - [Characterization of antagonistic and acid formation properties of Lactobacillus
      casei].
AB  - Cultural, morphologic, and biochemical characteristics of Lactobacillus casei
      were studied as well as their acid-forming and antagonistic activity and
      resistance to antibiotics. 60 cultures identified as L. caseiwere isolated from
      250 samples of sour-milk products and clinical specimens. All isolated strains
      had respectively high antagonistic activity regardless of their source.
      Dependence between antagonistic activity and acid formation was not detected.
      Conclusion about promise for using these lactobacilli for manufacturing of
      probiotics has been done.

PMID- 17523488
TI  - [Shigellosis in Karachaevo-Cherkes Republic in 1996-2005].
AB  - Incidence and etiologic structure of shigellosis in Karachaevo-Cherkes Republic
      for 10 years are analyzed and compared with same characteristics in Russia
      overall. Sharp rise of shigellosis cases number is detected in 2003-2005 as well
      as predominance of Shigella sonnei represented by biovar Ilg. It was shown that
      Shigella strains with different resistance to tetracycline and chloramphenicol
      circulate in Karachaevo-Cherkes Republic.

PMID- 17523489
TI  - [Use of antagonistic Bacillus subtilis bacteria for treatment of nosocomial
      urinary tract infections].
AB  - Effect of Bactisporin--a probiotic, containing spores of aerobic Bacillus
      subtilis 3H bacterium--for complex treatment of patients with nosocomial urinary
      tract infections was studied. 68 Cultures of different species of conditionally
      pathogenic bacteria were isolated from urine of the patients. Susceptibility of
      the isolated cultures to antibiotics before and after application of B. subtilis
      3H metabolites was determined. The metabolites were accumulated on potato-glucose
      agar (PGA) while bacterium was cultivated on kapron membranes placed on surface
      of the medium. Influence of obtained metabolites on isolated strains was assessed
      by cultivation of each strain in metabolites-rich PGA during 24 h. Metabolites of
      B. subtilis led to decrease in resistance of isolated uropathogenic microflora to
      antibiotics. Use of Bactisporin in complex treatment of nosocomial urinary tract
      infections resulted in accelerated elimination of causative microorganism.

PMID- 17523490
TI  - [Combined method of community-acquired pneumonia prevention in military staff].
AB  - Efficacy of pneumococcal polysaccharide vaccine "Pneumo 23" or its combination
      with food products prepared from vegetative material for prevention of community
      acquired pneumonias has been compared. Advantages of combined method of
      prophylaxis in setting where pneumonia caused by different pathogens have been
      noted. Variability in etiology of community-acquired pneumonia was demonstrated
      by serological tests of patients' blood. During spring-summer season antibodies
      to Mycoplasma pneumoniae, Chlamydia pneumoniae, and Streptococcus pneumoniae were
      detected in 25.9, 2.5, and 7.0% of the patients respectively. During autumn
      winter season antibodies to M. pneumoniae and S. pneumoniae were detected in 30.0
      and 50.0% of the patients respectively.

PMID- 17523491
TI  - [Molecular basis of bacteriocins production and activity].
AB  - Bacteriocins--bacterial proteins or peptides--are envisaged as candidates for the
      next generation of effective antimicrobials. Analysis of characteristics of
      natural and genetically engineered bacteriocins with regard to the molecular
      basis of their production and activity has been performed. Most bacteriocins have
      narrow spectrum of the inhibitory activity. Some of the broad-spectrum
      bacteriocins have circular molecular structure (C- and N-terminals of the
      aminoacid chain are joined by a peptide sequence). Fixed position of molecules'
      ends possibly accounts for the ability of the proteins to bind with various
      receptors on the surface of the target cells. Genes encoding bacteriocins and
      functionally associated proteins can be expressed in heterologous cells including
      eukaryotic cells. Also there were reports of changing bacteriocin characteristics
      by the use of site-specific mutagenesis.

PMID- 17523492
TI  - [Bacillus cereus enterotoxins].
AB  - Data about Bacillus cereus different enterotoxins including hemolysin (HBL),
      nonhemolytic enterotoxin (NHE), enterotoxin (T), and emesis-inducing thermostable
      enterotoxin (ETE) are summarized in the article. Information about synthesis of
      different diarrhea-inducing and emesis-inducing enterotoxins, methods of their
      purification, structure, functions, and mechanisms of action are presented.
      Commercial kits for identification of B. cereus enterotoxins causing food
      associated diarrhea are listed.

PMID- 17523493
TI  - [Identification of potential causative infectious agents of chronic prostatitis].
AB  - Analysis of the data on etiology and pathogenesis of inflammatory processes in
      prostate including acute and chronic prostatitis as well as chronic pelvic pain
      syndrome is presented. It has been noted that about 50% of men of fertile age had
      clinical signs of chronic prostatitis at least once in life and that more than
      60% of admissions to urologists in outpatient practices are related with clinical
      signs of chronic prostatitis. An appreciable decrease in quality of life similar
      to that due to myocardial infarction or Crohn's disease is observed in patients
      with chronic prostatitis. Prostatitis often has a chronic cyclic course with
      exacerbation and remission phases. Not rarely the disease has primary chronic
      course--without an apparent beginning as acute prostatitis. This leads to late
      diagnostics and difficulties with identification of etiologic factor, which
      commonly is a conditionally pathogenic microorganisms and mixed infections. Such
      difficulties can be a reason for inadequate treatment and complications of
      chronic prostatitis such as abscess, paraprostatitis, impotence, and infertility.

PMID- 17523494
TI  - Grateful patient programs: current trends, strategies and tactics.
AB  - This article explores the current trends, strategies and tactics in health care
      philanthropy regarding grateful patient programs. It is based on primary
      research, conducted through in-depth interviews and a survey of Association for
      Healthcare Philanthropy (AHP) members, to examine the many internal and external
      components that contribute to building a successful grateful patient fundraising
      program.

PMID- 17523495
TI  - Partnering with finance: a successful model for collaboration.
AB  - Faced with growing community health care needs and decreasing hospital operating
      surpluses, Banner Health turned to its foundation to "fill the gap" and support
      several new capital projects by increasing fundraising goals to unprecedented
      levels. In order to achieve these objectives, philanthropy is being integrated
      into the hospital system's strategic financial planning process as a recognized
      revenue source. This evolution has required a new model of collaboration between
      the hospital's finance and philanthropic organizations, and the development of a
      common language for more effective and accurate performance measurement.

PMID- 17523496
TI  - Moves management: chess or dancing?
AB  - Major gift professionals have benefited for many years from using the Moves
      Management system to help plan and track the activities of the donor cultivation
      cycle. But what are the implications of this process if it is "played" like a
      chess game? Only by shifting the focus from "chess moves" which are "all about
      us" to "dance steps" which are "all about them," can we develop close, meaningful
      and successful relationships with our donors.

PMID- 17523497
TI  - Hello, fellow! One woman's foray into AHP Fellow certification.

PMID- 17523498
TI  - Preparing for the future.

PMID- 17523499
TI  - Fundraising excellence: enabling a dynamic fund development program.

PMID- 17523500
TI  - More on astigmatism analysis.

PMID- 17523501
TI  - Influence of epi-LASIK and alcohol-assisted LASEK on retinal nerve fiber layer
      thickness.

PMID- 17523502
TI  - Customized LASIK treatment for myopia based on preoperative manifest refraction
      and higher order aberrometry: the Rochester nomogram.
AB  - PURPOSE: To develop and test the efficacy of myopic treatment, based on
      preoperative manifest refraction and higher order aberrations, in enhancing the
      postoperative refractive error following customized LASIK treatment and compare
      results with the manufacturer-recommended sphere offset Zyoptix treatment
      nomogram, which does not account for the preoperative higher order aberrations.
      METHODS: One hundred seventy-five myopic eyes (89 patients) were treated based on
      the Rochester nomogram, which specified the amount of myopia to be treated based
      on preoperative manifest refraction and higher order aberrations, including third
      order aberrations and spherical aberration. Postoperative refractive error was
      measured at 1 month and compared to that theoretically estimated with the Zyoptix
      nomogram. RESULTS: The mean preoperative sphere and cylinder were -4.52 +/- 2.05
      diopters (D) and -0.81 +/- 0.70 D, respectively. The mean postoperative spheres
      were +0.04 +/- 0.33 D and +0.31 +/- 0.54 D, using the Rochester and Zyoptix
      nomograms, respectively. The mean postoperative spherical equivalent refractions
      were -0.11 +/- 0.34 D and +0.15 +/- 0.53 D using the Rochester and Zyoptix
      nomograms, respectively. The Rochester nomogram reduced the range of
      postoperative spherical equivalent to +/- 1.00 D, which was significantly better
      than that using the Zyoptix nomogram (t = 5.46, P < .0001), which would have
      resulted in 8% of eyes with a postoperative spherical equivalent refraction > +/-
      1.00 D. Using the Rochester nomogram, 93.1% of eyes attained a postoperative UCVA
      > or = 20/20. The percentage of postoperative hyperopic overcorrection decreased
      to 2.8% in the Rochester nomogram group from 22.3% using the Zyoptix nomogram,
      which only adjusts spherical values based on preoperative sphere and does not
      account for preoperative aberrations. CONCLUSIONS: The Rochester nomogram
      compensates for the effect of preoperative higher order aberrations on sphere and
      provided reduced range of postoperative spherical equivalent refraction.

PMID- 17523503
TI  - Diurnal variation of higher order aberrations in human eyes.
AB  - PURPOSE: To evaluate diurnal variation of higher order aberrations in human eyes.
      METHODS: A prospective study of 20 myopic eyes was performed. Cycloplegic
      aberrometry (Zywave) and refraction were measured at 2-hour intervals for five
      time points beginning at 10:00 AM. Changes in measured magnitude for third and
      fourth order Zernike coefficients were compared over time. Analysis of variance
      (ANOVA) was performed to test for statistically significant differences across
      time points for each Zernike coefficient. A separate prospective study was
      performed of 11 myopic eyes to determine and compare diurnal variation with the
      repeatability coefficient of individual Zernike coefficients measured using the
      Zywave aberrometer. RESULTS: Mean refraction was -0.75 +/- 1.25 diopters (D)
      sphere and -0.57 +/- 0.43 D cylinder. No statistically significant change (ANOVA)
      was noted over the period of observation for any individual Zernike coefficients.
      Only Z3(-3) (vertical trefoil) showed an average increase of 0.029 microm (P =
      .98) towards the end of the day; however, this trend was not statistically
      significant. The standard deviation of individual Zernike coefficients ranged
      from 0.035 microm (Z4(4)) to 0.165 microm (Z3(-1)). CONCLUSIONS: No statistically
      significant diurnal variation of higher order aberrations was measured by Zywave
      aberrometer. The trend of Z3(-3) increasing later in the day was most likely a
      Zywave measurement error artifact.

PMID- 17523504
TI  - Improvement of visual acuity following refractive surgery for myopia and myopic
      anisometropia.
AB  - PURPOSE: To test the hypothesis that anisometropic adults without significant
      amblyopia suffer from mild visual impairment probably due to aniseikonia, which
      might be improved by corneal refractive surgery. METHODS: Fifty-seven patients
      presenting with myopic anisometropia > or = 3.25 diopters (D) and 174 myopic
      controls appropriate for refractive surgery were included. Photorefractive
      keratectomy (PRK) or LASIK was performed on 57 anisometropic eyes. As 43 of the
      174 myopic control patients had bilateral surgery, PRK or LASIK was performed on
      217 myopic control eyes. Best spectacle-corrected visual acuity (BSCVA),
      refraction, and refractive correction were measured preoperatively and at 1, 3, 5
      to 7, 8 to 13, and 25 months following surgery. RESULTS: Preoperative mean
      spherical equivalent was -7.20 +/- 2.40 D for anisometropic patients and -6.40 +/
      1.90 D for myopic patients. At 8 to 13 months postoperatively, when 23 (40%)
      anisometropic eyes and 94 (43%) myopic eyes were examined, the mean spherical
      equivalent refractions were -0.80 +/- 1.60 D and -0.30 +/- 0.60 D, respectively.
      Preoperatively, the mean BSCVA on a logMAR scale was -0.0143 +/- 0.0572 (Snellen
      0.98 +/- 0.12) in the anisometropic group and 0.0136 +/- 0.0361 (Snellen 1.04 +/-
      0.09) in the control group (P = .001). Eight to 13 months postoperatively, these
      values were 0.0076 +/- 0.0659 (Snellen 1.03 +/- 0.15) and 0.0495 +/- 0.0692
      (Snellen 1.13 +/- 0.18) and this difference remained statistically significant (P
      = .012). For the myopic patients, the improvement in BSCVA reached almost maximum
      at 3 months, and this improvement was found to be highly significant 3 months
      after surgery (P = .001). The improvement in BSCVA was significantly slower for
      anisometropic patients and became statistically significant only after 8 to 13
      months postoperatively (P = .041). CONCLUSIONS: Anisometropia reduces visual
      acuity in the more myopic eye and can be at least partially reversed by
      refractive correction. The slower improvement in BSCVA for anisometropic patients
      suggests plastic changes in the visual cortex following refractive surgery.

PMID- 17523505
TI  - Measurement of angle kappa with synoptophore and Orbscan II in a normal
      population.
AB  - PURPOSE: To obtain normative values of angle kappa in a normal population by
      synoptophore and Orbscan II and to compare the reliability of these devices.
      METHODS: Three hundred consecutive healthy individuals were enrolled in the
      study. A complete orthoptic and ophthalmologic examination was performed.
      Synoptophore and Orbscan II corneal topography were used to measure angle kappa.
      To evaluate the association of the angle kappa and refraction measures,
      individuals were further classified according to the degree of myopia and
      hyperopia. The spherical equivalent error measures were grouped into six
      categories: > or = -3.00 diopters (D); -2.75 to -1.50 D; -1.25 to -0.50 D; +0.50
      to +1.25 D; +1.50 to +2.75 D; and > or = +3.00 D. Paired t test and Pearson's
      correlation test were used for statistical analysis. RESULTS: The mean age of the
      individuals was 28.74 +/- 1.63 years (range: 20 to 40 years). The angle kappa
      values obtained by synoptophore and Orbscan II were normally distributed. In the
      myopic group, angle kappa values decreased significantly towards negative
      refractive errors. In contrast, a correlation existed between large positive
      angles and positive refractive errors in the hyperopic group. Angle kappa values
      obtained by Orbscan II were significantly higher in all groups when compared to
      synoptophore (P < .0001). A significant correlation was noted between
      synoptophore and Orbscan II measurements (r = 0.932, P < .0001). CONCLUSIONS: A
      significant correlation exists between positive refractive errors and large
      positive angle kappa values. Refractive surgeons must take into account angle
      kappa, especially in hyperopic patients, to avoid complications related to
      decentration of the ablation zone.

PMID- 17523506
TI  - Correlation between attempted correction and keratometric refractive index of the
      cornea after myopic excimer laser surgery.
AB  - PURPOSE: Given that the standard keratometric refractive index of 1.3375 is no
      longer valid after excimer laser surgery, we aimed to investigate how this value
      changes postoperatively and if any correlation to the attempted correction
      exists. METHODS: The pre- and postoperative data of 98 patients who underwent
      either myopic photorefractive keratectomy (PRK) or LASIK were reviewed. Using
      postoperative videokeratography, the corneal radius (r) was obtained; the
      corrected corneal power (Pc) was measured by separately calculating the dioptric
      power of the anterior and posterior corneal surfaces. The postoperative index of
      refraction (n(post)) was derived from these values using the formula: n(post) =
      (rPc) +1. RESULTS: As the amount of refractive change increases, n(post)
      progressively decreases (P < .0001, r = 0.9581). Linear regression provided the
      subsequent formula to calculate the postoperative index of refraction: n(post) =
      1.338 + 0.0009856 x attempted correction. CONCLUSIONS: Myopic PRK and LASIK
      induce a decrease in the keratometric refractive index. This reduction correlates
      to the amount of attempted correction. When the latter is known, calculating
      n(post) may enable the measurement of corneal power and thus provide an
      additional method for calculating intraocular lens power in eyes that have
      undergone myopic PRK or LASIK.

PMID- 17523507
TI  - Effect of punctal plugs in patients with low refractive errors considering
      refractive surgery.
AB  - PURPOSE: To study the effect of punctal plug placement in patients undergoing
      refractive surgery for correction of poor vision. METHODS: A retrospective study
      was performed of 12 patients (21 eyes) who presented for initial refractive
      surgery or retreatment after LASIK or photorefractive keratectomy to improve
      visual acuity. Uncorrected visual acuity (UCVA) was documented in each eye. If
      tear normalization test was positive (indicating dry eye), silicone punctal plugs
      were placed in the lower lids of both eyes. Subjective patient UCVA and Snellen
      UCVA were assessed at 1 month. RESULTS: At 1 month, two eyes improved by three
      Snellen lines, nine eyes improved by two lines, seven eyes improved by one line,
      and three eyes remained unchanged. Uncorrected visual acuity was considered
      statistically significant (P < .0001) using the paired t test. No eye
      demonstrated decrease in visual acuity. One patient experienced punctal plug
      extrusion in both eyes. No other adverse outcomes were reported. One patient
      pursued additional refractive surgery after plug placement. No patient requested
      plug removal. CONCLUSIONS: Patients with low refractive errors note improvement
      in visual acuity after punctal plug placement.

PMID- 17523508
TI  - Buttonholes during LASIK: etiology and outcome.
AB  - PURPOSE: To report the clinical features and outcome of eyes with flap buttonhole
      during LASIK. METHODS: A retrospective review was performed to identify eyes that
      developed flap buttonhole during Hansatome microkeratome translation. Pre-, intra
      , and postoperative data were obtained to identify factors predictive of
      buttonhole. RESULTS: Five patients with buttonhole were identified from June 2001
      through September 2002 (5 [0.06%] eyes of 7672 primary LASIK procedures). Mean
      patient age was 49.2 +/- 11.3 years (range: 37 to 66 years). Mean preoperative
      spherical equivalent refraction was 4.92 +/- 2.90 diopters (D) (range: -2.25 to 
      9.50 D). Mean keratometry was 45.59 +/- 1.15 D (range: 43.90 to 47.60 D). All 5
      flap buttonholes occurred in the second of 2 consecutively treated eyes (P =
      .03). Buttonhole occurred in 2 (0.26%) of 778 eyes where the 160-microm
      microkeratome plate was used, and 3 (0.06%) of 4350 eyes where the 180-microm
      plate was used (P = .16). Two eyes received laser ablation at the time of
      buttonhole formation. In the untreated cases, the buttonhole flap itself caused a
      myopic spherical change of -0.50 D and 0.70 D of astigmatism. One of 5 eyes lost
      2 lines of best spectacle-corrected visual acuity; this eye received laser
      ablation immediately after buttonhole formation. CONCLUSIONS: Buttonholes are
      significantly more likely to occur in the second of two consecutively treated
      eyes. A new blade for the second eye when the flap in the first eye appears to be
      thin should be considered. Caution should be exercised when considering laser
      ablation immediately following buttonhole formation.

PMID- 17523509
TI  - Histological changes and unscheduled DNA synthesis in the rabbit cornea following
      213-nm, 193-nm, and 266-nm irradiation.
AB  - PURPOSE: To examine the acute outcome of corneal irradiation in adult rabbits for
      193-, 213-, and 266-nm laser wavelengths. METHODS: Animals were randomly
      allocated to one of three groups and were treated with 213-nm quintupled Nd:YAG
      laser, a 193-nm excimer laser, or a 266-nm quadrupled Nd:YAG laser (n = 6 per
      group, two exposure durations). Thermal damage was assessed histologically and
      the extent of DNA damage estimated by measuring unscheduled DNA synthesis in
      corneal epithelial and stromal cells using 3H thymidine autoradiography. RESULTS:
      For the 193- and 213-nm groups, irradiation did not induce thermal damage.
      Moreover, cells displaying unscheduled DNA synthesis represented < 4% of the
      total cell numbers with no difference between groups (P > .05). By contrast, the
      266-nm laser led to stromal melting and vacuolation; unscheduled DNA synthesis
      levels were elevated over the other groups (P < .05). CONCLUSIONS: Corneal laser
      ablation with the 213-nm Nd:YAG laser resulted in similarly low levels of thermal
      and DNA damage to those produced using the clinically accepted 193-nm excimer
      laser.

PMID- 17523510
TI  - Description, etiology, and prevention of an outbreak of diffuse lamellar
      keratitis after LASIK.
AB  - PURPOSE: To describe an outbreak of diffuse lamellar keratitis (DLK) and provide
      a hypothesis about the etiology. METHODS: A retrospective analysis was carried
      out on 328 eyes of 220 patients who underwent LASIK over 9 months. The occurrence
      of DLK using two different methods of cleaning and sterilizing surgical
      instruments and an autoclave reservoir were analyzed. Microbial analyses were
      carried out by two laboratories on samples obtained from the original autoclave
      reservoir and tubing. A chi-square test was used to compare qualitative values.
      The Student t test was used to compare numerical values. RESULTS: Forty-six
      (24.5%) of 188 cases of DLK were diagnosed. Sphingomona paucimobilis and
      Burkholderia pickettii were isolated in the reservoir of the steam sterilizer.
      Electron microscopy revealed gram-negative microbes on the tubing walls. After
      changing the reservoir of the steam sterilizer and implementing a new cleaning
      and sterilization protocol based on air-drying the instruments and draining and
      drying the reservoir of the sterilizer, the occurrence of DLK stopped. No
      statistically significant correlation was noted between the occurrence of DLK and
      gender, age, or volume of tissue removed. CONCLUSIONS: Data obtained during this
      DLK outbreak support the theory that a bacterial endotoxin, which can survive
      short-cycle steam sterilization, could be responsible for an outbreak of DLK. We
      recommend cleaning and sterilization protocols based on air-drying surgical
      instruments and leaving the reservoirs completely dry at the end of each surgical
      day.

PMID- 17523511
TI  - Comparison of anterior chamber depth measurement between Orbscan IIz and
      ultrasound biomicroscopy.
AB  - PURPOSE: To compare the measurement of anterior chamber depth exclusive of
      corneal thickness using Orbscan IIz and ultrasound biomicroscopy (UBM) and
      evaluate the repeatability of each method. METHODS: Three consecutive
      measurements of anterior chamber depth were prospectively performed using Orbscan
      IIz and Paradigm 50-MHz UBM in 40 eyes in 20 individuals. Mean values were
      compared using the paired t test. For 12 eyes in 6 individuals, anterior chamber
      depth measurements were performed 5 times to estimate the repeatability of each
      method by a coefficient of variation. Refractive errors were measured to
      correlate with anterior chamber depth. RESULTS: The mean anterior chamber depth
      was 2.82 +/- 0.46 mm with the Orbscan IIz and 2.91 +/- 0.43 mm in UBM. This
      difference was statistically significant (P < .001), but not clinically
      meaningful. The coefficient of variation was 1.15% and 1.10% in Orbscan IIz and
      UBM, respectively. A negative correlation between anterior chamber depth and
      spherical equivalent refraction was noted within the range of -5.50 to +3.00
      diopters. CONCLUSIONS: The mean anterior chamber depth of Orbscan IIz was 0.087
      mm less than that of UBM. Both methods were precise. Orbscan IIz seems to be a
      useful and more convenient method to measure anterior chamber depth for phakic
      intraocular lens implantation.

PMID- 17523512
TI  - Takagi Glare Tester CGT-1000 for contrast sensitivity and glare testing in normal
      individuals and cataract patients.
AB  - PURPOSE: To investigate the sensitivity and repeatability of the Takagi Contrast
      Glare Tester CGT-1000 in normal individuals and those with cataracts. METHODS: A
      prospective observational study was performed. The Takagi Contrast Glare Tester
      measures contrast sensitivity (CS) at 6 target sizes and 13 contrast levels (2.00
      to 0.34 logCS). Testing follows a method of descending limits paradigm with a
      single reversal determining threshold. The CGT-1000 was administered with and
      without glare in 95 eyes of 61 cataract patients and 13 controls. The percentage
      floor (unable to see the highest contrast) and ceiling (able to see the lowest
      contrast) effects and correlations between CS and cataract grades were
      determined. The repeatability was evaluated using Bland-Altman limits of
      agreement and expressed as the coefficient of repeatability (COR). Factor
      analysis was used to test for redundancy within the 6 spatial frequencies.
      RESULTS: In normal individuals, a high rate of ceiling effect varying with target
      size was noted--for 6.3 degrees, 4.0 degrees, 2.5 degrees, 1.6 degrees, 1.0
      degrees, 0.7 degrees, ceiling effects were 68%, 58%, 18%, 11%, 4%, 2%,
      respectively, for no glare, and 47%, 42%, 8%, 2%, 2%, 2%, respectively, with
      glare. In cataract patients, floor effects were noted--3%, 0%, 3%, 7%, 19%, 62%,
      respectively, for no glare, and 3%, 3%, 6%, 14%, 44%, 79%, respectively, with
      glare. Correlations with cataract grades ranged from 0.10 to 0.61, being best for
      nuclear cataract. Repeatabilities expressed as COR were +/- 0.11, +/- 0.14, +/-
      0.28, +/- 0.38, +/- 0.38, +/- 0.47 logCS, respectively. All spatial frequencies
      loaded heavily on one factor, indicating no gain in information from testing
      multiple target sizes. CONCLUSIONS: Sensitivity to the presence of cataract was
      good, but ceiling effects in normal individuals and floor effects in cataract
      patients limit accuracy. Repeatability was poor, but could be improved by testing
      less spatial frequencies more rigorously.

PMID- 17523513
TI  - Limbal relaxing incisions to correct corneal astigmatism during
      phacoemulsification.
AB  - PURPOSE: To evaluate the safety and efficacy of limbal relaxing incisions for the
      correction of corneal astigmatism during phacoemulsification. METHODS: Fifty eyes
      of 37 patients (mean age 66.5 years, range: 45 to 80 years) with cataract and
      coexisting topographic astigmatism were included in the study. Eyes were randomly
      divided into two groups: eyes that underwent cataract surgery with limbal
      relaxing incisions (cataract LRI group) and eyes that underwent cataract surgery
      only (control group). All limbal relaxing incisions were performed during
      phacoemulsification. Best spectacle-corrected visual acuity (BSCVA), uncorrected
      visual acuity (UCVA), and corneal topography were recorded preoperatively and 1,
      3, and 6 months postoperatively. RESULTS: A statistically significant improvement
      in BSCVA was seen in the cataract LRI eyes from 0.9 +/- 0.7 preoperatively to 0.1
      +/- 0.1 at 1, 3, and 6 months postoperatively (P < .01). A statistically
      significant improvement in BSCVA was seen in control eyes from 0.8 +/- 0.6 before
      surgery to 0.2 +/- 0.2 at 1, 3, and 6 months after surgery (P < .01). No
      difference in postoperative BSCVA was noted between the groups. A statistically
      significant reduction in the mean topographic astigmatism was seen in the
      cataract LRI eyes from 1.93 +/- 0.58 diopters (D) preoperatively to 1.02 +/- 0.60
      D 6 months postoperatively (P < .05). The control eyes did not show a
      statistically significant change in topographic astigmatism. CONCLUSIONS: Limbal
      relaxing incisions performed during phacoemulsification surgery appear to be a
      safe, effective, and stable procedure to reduce pre-existing corneal astigmatism.

PMID- 17523514
TI  - Corneal asphericity and spherical aberration.
AB  - PURPOSE: To summarize the various values of asphericity in different notations
      and present how corneal asphericity, corneal curvature, and entrance pupil
      diameter influence the longitudinal spherical aberration of the anterior corneal
      surface. METHODS: After the conversion factors between the different asphericity
      notations were described, finite ray tracing through a conic section that models
      the anterior cornea profile was performed. The anterior cornea was given a range
      of curvatures and asphericities and a range of entrance pupil diameters. RESULTS:
      If the value of asphericity remains constant, longitudinal spherical aberration
      increases with the square of the entrance pupil diameter. If the pupil diameter
      remains fixed, the spherical aberration becomes a function of the value of
      asphericity, the refractive index, and the radius of curvature. If the refractive
      index, pupil diameter and asphericity are considered constant, the spherical
      aberration will decrease if the corneal surface flattens and increase as the
      cornea becomes steeper. In this way, with the same shape factor and with the same
      starting apical radius, longitudinal spherical aberration became a function of
      the surgically induced refractive change. With equal curvature, the longitudinal
      spherical aberration becomes negative if the surface is more prolate than perfect
      Cartesian oval; it will become positive if it is less prolate, spherical, or
      oblate. CONCLUSIONS: A conversion chart for corneal asphericity notations with
      the corresponding spherical aberration and a diagram reporting values of
      asphericity necessary to maintain the physiological value of the corneal
      spherical aberration after refractive procedures may be useful tools in corneal
      surgery.

PMID- 17523515
TI  - Effect on astigmatism of the location of clear corneal incision in
      phacoemulsification of cataract.
AB  - PURPOSE: To investigate the refractive results of clear corneal incision
      performed at the steepest meridian of pre-existing corneal astigmatism. METHODS:
      One hundred eighty-two patients with astigmatism > 0.75 diopters (D) were
      evaluated. Superior, temporal, nasal, superotemporal, or superonasal clear
      corneal incisions were performed at the steep meridian. Refraction, visual
      acuity, and topography values were evaluated, and changes in surgically induced
      astigmatism were calculated by vector analysis using the Fourier formula. Paired
      t test was used to compare mean values. RESULTS: Postoperative cylinder values
      showed minor changes in all groups, except the nasal group. Nasal incision
      increased preoperative cylinder from 1.13 D to 1.83 D 6 months after surgery.
      Temporal and superotemporal incisions resulted only in small astigmatic changes.
      Conversely, superior, superonasal, and nasal incisions induced more pronounced
      astigmatism. CONCLUSIONS: Performing clear corneal incision for
      phacoemulsification of cataract at the steep meridian resulted in small changes
      with temporal incisions, whereas nasal incisions resulted in higher surgically
      induced astigmatism.

PMID- 17523516
TI  - Retreatment after LASIK using epithelial ablation alone.
AB  - PURPOSE: Retreatments after refractive surgery may be associated with
      complications similar to the original surgical procedure. Excimer laser ablation
      of the epithelium may be associated with fewer complications and may prevent the
      need for flap-lift retreatment after LASIK. METHODS: A retrospective chart review
      identified eyes that had undergone epithelial retreatments after primary LASIK.
      Treatment was performed with excimer laser correction on a dry intact epithelium.
      RESULTS: Of the 27 eyes that were treated in this fashion, 8 (29.6%) eyes went on
      to subsequent flap-lift retreatment. The most common complication at 1 day was
      punctate keratopathy (7 eyes, 25.9%). No eyes lost best spectacle-corrected
      visual acuity during follow-up. CONCLUSIONS: The high rate of subsequent flap
      lift retreatment, as well as the lack of statistically significant changes in
      refractive error, will limit the usefulness of epithelial retreatments. Because
      of the low incidence of complications, improvement in a small number of patients,
      and the lack of desire of some patients to undergo further flap-lift retreatment,
      epithelial retreatment may be useful in some eyes with minimal residual
      refractive error after LASIK.

PMID- 17523517
TI  - Hyperopic keratoconus.
AB  - PURPOSE: To report three patients (four eyes) with hyperopic keratoconus.
      METHODS: Patients were evaluated with corneal curvature topography, ultrasonic
      pachymetry, and rotating Scheimpflug camera. RESULTS: One patient, without other
      risk factors, developed unilateral ectasia after LASIK following primary
      hyperopic ablation in an eye suspicious for keratoconus. Two additional hyperopic
      patients (three eyes) had curvature and elevation findings compatible with
      keratoconus. CONCLUSIONS: Although rare, keratoconus could present in hyperopia.
      If keratoconus is suspected, we suggest avoidance of LASIK and its potential for
      development of corneal ectasia.

PMID- 17523518
TI  - Corneal suture for the correction of hyperopia following radial keratotomy.
AB  - PURPOSE: To report the visual and refractive changes observed after double
      concentric corneal suture to correct hyperopic shift after radial keratotomy
      (RK). METHODS: This retrospective consecutive case series comprised 17 eyes (15
      patients) that underwent two concentric corneal sutures (modified Grene Lasso
      suture) to correct hyperopic shift after RK. All surgeries were performed by the
      same surgeon between 2000 and 2003. RESULTS: The mean time after RK was 11.6 +/-
      3.2 years. The mean follow-up was 20.3 +/- 11.3 months. The spherical equivalent
      refraction was reduced from a preoperative mean of +4.38 +/- 2.87 diopters (D) to
      -0.54 +/- 2.59 D at last postoperative follow-up (P < .001). No statistically
      significant difference was observed in mean refractive astigmatism before and
      after the corneal suture (P = .15). Before surgery, no eye presented with best
      spectacle-corrected visual acuity (BSCVA) > or = 20/20. At final follow-up, 3
      (17.6%) eyes attained this level. Seven (41.2%) eyes improved their BSCVA by > or
      = 2 Snellen lines. One (5.9%) eye lost 2 Snellen lines of BSCVA. CONCLUSIONS:
      Corneal suture can be used to correct RK-induced hyperopia, improving the corneal
      asphericity in an attempt to stabilize these corneas. It appeared to be effective
      even for high degrees of hyperopia and in cases with associated irregular
      astigmatism or open incisions.

PMID- 17523519
TI  - New directions for youth development. Transition or eviction. Youth exiting care
      for independent living.

PMID- 17523520
TI  - Youth leaving care: how do they fare?
AB  - This chapter summarizes recent Canadian and international research on the
      outcomes for youth after they age out of the child welfare system. It paints a
      disturbing picture for this small and vulnerable population. Youth leaving care
      face many challenges in making the transition from state care to independence and
      adulthood. They bear the emotional scars of childhood neglect or abuse. They do
      not have a family support network, have limited or no financial resources, are
      often lacking in life skills, and usually have not completed school. Despite
      these setbacks, we expect them to function independently once they reach age
      eighteen. Research shows that once youth leave care, they do not fare as well as
      their peers. They are at much greater risk of relying on social assistance,
      becoming homeless, engaging in substance abuse, becoming single parents,
      experiencing mental health problems, or coming into contact with the criminal
      justice system. Some youth aging out, however, have more successful transitions.
      These typically have completed high school, have role models, have access to
      postsecondary opportunities, refrain from alcohol or drug use, and obtain life
      skills and independent living training. Having stable placements while in care is
      also critical in ensuring more positive outcomes. Canada does not have the
      capacity to track the outcomes of youth as they leave the child welfare system,
      nor can it identify the types of interventions showing the most promise in
      helping them achieve better outcomes. Canadian governments need to improve their
      transitional planning for youth in care who are approaching the age of majority.
      Some recommendations include extending the age for services and financial
      assistance to age twenty-four, developing standards to prepare youth for leaving
      care, and exploring ways to enable youth to pursue higher education or training.
      Finally, Canada should develop a national longitudinal survey to monitor the
      outcomes of youth after they leave care.

PMID- 17523521
TI  - The transition from state care to adulthood: international examples of best
      practices.
AB  - Around the world, the transition from adulthood is a difficult time for many
      youth. It is even more difficult for those who are transitioning to adulthood
      without the benefit of a support network full of family and friends. Youth
      leaving state care face a transition to independence and adulthood without many
      of the skills and supports most others take for granted. Preparedness is key to a
      successful transition, and youth leaving state care tend to be lacking it. In
      order for youth to truly be prepared for the transition process, they must have
      support in key areas of their lives: relationships, education, housing, life
      skills, identity, youth engagement, emotional healing, and adequate financial
      support. Without these supports, the dismal outcomes for youth transitioning to
      adulthood will remain unchanged. The United States, England, and Australia have
      successful programs targeting youth as they transition out of state care. These
      initiatives bring together and address the variety of needs of this unique
      population and aim to improve outcomes. While many of these programs and policies
      are in their infancy, they show promising results, and each contributes valuable
      experience to successfully working with youth through this tough transition.

PMID- 17523522
TI  - The role of housing in the transition process of youth and young adults: a twenty
      year perspective.
AB  - Lighthouse Youth Services in Cincinnati, Ohio, began placing foster youth, ages
      sixteen to eighteen, in individual apartments and other living arrangements in
      1981 as a way of preparing them for life after foster care. The program has
      assisted over thirteen hundred youth and their children using scattered-site
      apartments, shared homes, roommate situations, host homes, and subsidized
      housing. The agency works with referring agencies to develop a transition plan
      one youth at a time and allows youth to move along a continuum of housing options
      depending on their level of functioning and behavior. Aftercare services assist
      youth for years after they leave custody. This chapter includes some case studies
      and summarizes the author's observations from running the program for the past
      twenty years.

PMID- 17523523
TI  - Transition without status: the experience of youth leaving care without Canadian
      citizenship.
AB  - The origins of the project reviewed in this chapter lie in discussions with a
      Toronto agency that has a mandate to serve youth in transition from the care of
      the Children's Aid Society. This service system, also known in various
      jurisdictions as child welfare, child protection, or foster care, includes among
      its clients children and youth who are living in Canada without legal Canadian
      status. This could have occurred because the child arrived alone and was taken
      into care on arrival or because the child arrived with a family but was taken
      into care before status was obtained. While the child is in care, this lack of
      status is relatively inconsequential in that health, educational, and other
      services are provided through the Children's Aid Societies. Once the transition
      is made from care, the youth's vulnerability increases dramatically if legal
      status has not been obtained. Health services, educational opportunities, and
      legal employment are often beyond reach, and the youth is subject to deportation.
      The major objectives of the project were to explore the national and
      international literature to discover the dimensions of this issue, interview
      youth and service providers to gain insight into their experience, and discover
      ways to minimize the number of youth who leave care without having obtained
      status.

PMID- 17523524
TI  - Promoting autonomous functioning among youth in care: a program evaluation.
AB  - Over the past few years, considerable research has highlighted the challenges
      posed by social reinsertion of youth. For youth who leave an alternative living
      environment at the outset of adulthood, this integration is all the more
      difficult on account of psychosocial and health factors and a lack of support in
      preparing for independent living and employment requirements. Although they
      possess various qualifications and resources for making this difficult
      transition, many find themselves relying on public-funded services as they enter
      adulthood. After a brief outline of the contextual organization of youth
      protection offered in Quebec, the author presents an intervention program that
      aims to prepare youth in high-risk categories for social reintegration and
      independent living. This is followed by a presentation of preliminary results
      stemming from a three-year pilot study and an outline for intervention and
      support for troubled youths who are entering adulthood.

PMID- 17523525
TI  - Juvenile offenders and independent living: an Irish perspective on program
      development with St. Xavier's.
AB  - This chapter views a specific population within the Irish social care system and
      draws from the authors' collective experience in relation to young offenders who
      are leaving care. It describes how effective program development for these youth
      is considered crucial to their long-term success and permeates all good practice.

PMID- 17523526
TI  - The Scottish perspective: a pathway to progress?
AB  - This chapter provides a historical overview of the development of care and
      aftercare practices in Scotland. It highlights significant developments in
      legislation and social policy and offers a critical analysis that draws on the
      author's experience as a practitioner.

PMID- 17523527
TI  - Using youth expertise at all levels: the essential resource for effective child
      welfare practice.
AB  - This chapter highlights the importance of ensuring that youth are partners in
      every aspect of service planning at individual and program levels. The author
      outlines this significant and recent development in the field of transitional
      living services and provides recommendations for meaningful youth involvement at
      both the micro and the macro levels.

PMID- 17523528
TI  - Afterword: Aging out of care--toward realizing the possibilities of emerging
      adulthood.

PMID- 17523529
TI  - Arresting death: saving 100,000 lives.
AB  - In January 2005, the Institute for Healthcare Improvement asked the nation's
      hospitals to voluntarily implement six specific care practices to prevent 100,000
      unnecessary patient deaths by June 2006. Find out how they not only met, but
      exceeded, their goal.

PMID- 17523530
TI  - A lifetime's work.

PMID- 17523531
TI  - Future Focus. Interview by Mary Grayson.

PMID- 17523532
TI  - Enhancing the board's role in quality.
AB  - Four hospital systems--two in Michigan and two in California--are participating
      in a research project to find new ways for the board to take a more active role
      in quality oversight and leadership.

PMID- 17523533
TI  - Board orientation: a continuing process.

PMID- 17523534
TI  - Martin Payson: a second career in hospital turnarounds.

PMID- 17523535
TI  - Making the case for conflict.

PMID- 17523536
TI  - General obligation bonds can meet capital shortfalls.

PMID- 17523537
TI  - 2007's top 10 governance trends.

PMID- 17523538
TI  - Occurrence and genetic typing of infectious hematopoietic necrosis virus in
      Kamchatka, Russia.
AB  - Infectious hematopoietic necrosis virus (IHNV) is a well known rhabdoviral
      pathogen of salmonid fish in North America that has become established in Asia
      and Europe. On the Pacific coast of Russia, IHNV was first detected in hatchery
      sockeye from the Kamchatka Peninsula in 2001. Results of virological examinations
      of over 10,000 wild and cultured salmonid fish from Kamchatka during 1996 to 2005
      revealed IHNV in several sockeye salmon Oncorhynchus nerka populations. The virus
      was isolated from spawning adults and from juveniles undergoing epidemics in both
      hatchery and wild sockeye populations from the Bolshaya watershed. No virus was
      detected in 2 other watersheds, or in species other than sockeye salmon. Genetic
      typing of 8 virus isolates by sequence analysis of partial glycoprotein and
      nucleocapsid genes revealed that they were genetically homogeneous and fell
      within the U genogroup of IHNV. In phylogenetic analyses, the Russian IHNV
      sequences were indistinguishable from the sequences of North American U genogroup
      isolates that occur throughout Alaska, British Columbia, Washington, and Oregon.
      The high similarity, and in some cases identity, between Russian and North
      American IHNV isolates suggests virus transmission or exposure to a common viral
      reservoir in the North Pacific Ocean.

PMID- 17523539
TI  - Experimental infection of Atlantic salmon Salmo salar pre-smolts by i.p.
      injection with new Irish and Norwegian salmonid alphavirus (SAV) isolates: a
      comparative study.
AB  - Atlantic salmon Salmo salar L. pre-smolts were experimentally infected with 2
      different isolates of salmonid alphavirus (SAV): a Subtype 1 isolate from Ireland
      and a Subtype 3 isolate from Norway. Sequential samples of tissue and blood were
      collected during a period of 20 wk post injection and subjected to virus
      isolation from kidney tissue and serum, detection of viral nucleic acid in heart
      tissue and serum by real-time RT-PCR, detection of specific antibodies by virus
      neutralisation assay, and histopathological examination. Successful reproduction
      of pancreas disease (PD) was obtained by intraperitoneal (i.p.) injection of both
      isolates. No mortality was observed post infection in either group, but typical
      PD histopathological lesions in heart and pancreas tissue were observed with both
      isolates. The prevalence and severity of lesions in the pancreas, heart, skeletal
      muscle and brain were similar in both groups with only subtle differences
      recorded. Re-isolation of virus from kidney tissue was performed at 7 and 14 d
      post infection (d p.i.) only and was positive for both test groups at both
      sampling points. Isolation of virus from sera from both groups was positive at 4
      to 14 d p.i., but was negative at later sampling points when antibody production
      had begun. Virus may be detected only during the acute phase using both methods.
      Specific neutralising antibodies could be detected for both test groups from Day
      21 p.i. until the end of the experiment at 140 d p.i. Peak antibody titres were
      seen 70 d p.i. Using real-time RT-PCR, pancreas disease virus (PDV)-specific RNA
      was detected frequently in serum samples up to 14 d p.i. and occasionally
      thereafter. In contrast, viral RNA could still be detected in the heart tissue of
      fish from both groups for at least 140 d p.i.

PMID- 17523540
TI  - Whitespotted puffer Arothron hispidus, a new host for lymphocystis in Qingdao
      Aquarium of China.
AB  - In April 2004 white nodular lesions were found on the fins of whitespotted puffer
      Arothron hispidus (Linnaeus). Diagnostic studies were carried out to confirm the
      disease using light and electron microscopy, histochemical methods and PCR. The
      results revealed that the nodules were composed of giant cells up to 400 microm
      in diameter. These cells were surrounded by a periodic acid-Schiff (PAS)-positive
      hyaline capsule containing dot-shaped, Feulgen-positive inclusion bodies in the
      cytoplasm and an irregular nucleus. Numerous virus particles 200 nm in diameter
      and with hexagonal profiles were observed in the cytoplasm. These features were
      consistent with those of lymphocystis disease. Additionally, based on the gene
      sequences of major capsid protein (MCP) of lymphocystis disease virus (LCDV) from
      Japanese flounder Paralichthys olivaceus, 2 pair primers were designed; after a
      nested PCR was performed for detection of LCDV in A. hispidus, a positive
      amplified product was obtained showing the presence of LCDV. Therefore, the white
      nodules were the lymphocystis lesions caused by LCDV infection and A. hispidus
      was demonstrated to be a new host for LCDV.

PMID- 17523541
TI  - PCR and in situ hybridization for the detection and localization of a new
      pathogen Francisella-like bacterium (FLB) in ornamental cichlids.
AB  - Archived formalin-fixed, paraffin-embedded tissues from 28 diseased ornamental
      cichlid fish associated with visceral granulomas were examined by polymerase
      chain reaction (PCR) and in situ hybridization (ISH) for detection of Francisella
      like bacteria (FLB). The 16S rDNA FLB-specific primer pair 180f/465r was used on
      naturally infected ornamental cichlids, resulting in 11 positive cases (39%).
      Using DNA probes, all 28 cases (100%) showed a positive reaction, and most
      labeled cells were observed in the visceral granulomas of infected individuals.
      FLB was detected in cells morphologically resembling epithelioid and endothelioid
      macrophages. ISH was more sensitive than PCR or routine histopathological
      examination, based on the examination of archived formalin-fixed, paraffin
      embedded tissues in this study. Furthermore, this technique located a new fish
      pathogen, FLB, in ornamental cichlids. The causative agent was similar to the
      pathogen inducing systemic granulomas in tilapia.

PMID- 17523542
TI  - Ultrastructure and molecular diagnosis of Spironucleus salmonis (Diplomonadida)
      from rainbow trout Oncorhynchus mykiss in Germany.
AB  - Diplomonad flagellates infect a wide range of fish hosts in aquaculture and in
      the wild in North America, Asia and Europe. Intestinal diplomonad infection in
      juvenile farmed trout can be associated with morbidity and mortality, and in
      Germany, diplomonads in trout are commonly reported, and yet are poorly
      characterised. We therefore undertook a comprehensive study of diplomonads from
      German rainbow trout Oncorhynchus mykiss, using scanning and transmission
      electron microscopy, and sequencing of the small subunit (ssu) rRNA gene. The
      diplomonad was identified as Spironucleus salmonis, formerly reported from
      Germany as Hexamita salmonis. Our new surface morphology studies showed that the
      cell surface was unadorned and a caudal projection was present. Transmission
      electron microscopy facilitated new observations of functional morphology,
      including vacuoles discharging from the body surface, and multi-lobed apices of
      the nuclei. We suggest the lobes form, via hydrostatic pressure on the
      nucleoplasm, in response to the beat of the anterior-medial flagella. The lobes
      serve to intertwine the nuclei, providing stability in the region of the cell
      exposed to internal mechanical stress. The ssu rRNA gene sequence clearly
      distinguished S. salmonis from S. barkhanus, S. salmonicida, and S. vortens from
      fish, and can be used for identification purposes. A 1405 bp sequence of the ssu
      rRNA gene from S. salmonis was obtained and included in a phylogenetic analysis
      of a selection of closely related diplomonads, showing that S. salmonis was
      recovered as sister taxon to S. vortens.

PMID- 17523543
TI  - Histopathological and ultrastructural observations of metacercarial infections of
      Diplostomum phoxini (Digenea) in the brain of minnows Phoxinus phoxinus.
AB  - The spatial distribution and histopathological changes induced by metacercariae
      of the digenean trematode Diplostomum phoxini (Faust, 1918) in the brains of
      European minnows Phoxinus phoxinus (L.) from the River Endrick, Scotland, were
      studied by light and electron microscopy. Post-mortem examination of a sample of
      34 minnows revealed that 50% (n = 17) of the population was infected with 13.7 +/
      2.6 (mean +/- SE; range 1 to 38) metacercariae per infected host. Serial
      histological sections of the infected minnow brains revealed that the
      metacercariae were unevenly distributed throughout the brain, with aggregations
      occurring in the cerebellum, the medulla oblongata and the optic lobes. In fish
      with highest intensities of infection, over 40% of the cerebellar area and about
      30% of the medulla oblongata area were occupied by larvae. Metacercariae disrupt
      the integrity of brain tissue, with individuals being found in small pockets
      surrounded by cellular debris. Metacercariae were rarely encountered on the
      surface of the brain. Electron microscopic examination of infection sites
      revealed that the granular layer surrounding metacercariae was necrotic,
      exhibited nuclear degradation and was marked by vacuolation of the cytoplasm.
      Rodlet cells, the only inflammatory cell types recorded in this study, were found
      only in parasitized brains and in close proximity to the teguments of
      metacercariae. It is hypothesised that secretions released from the teguments of
      metacercariae are a counter response to protect the metacercariae from the fish
      brain's cellular defence mechanisms.

PMID- 17523544
TI  - Enterospora canceri n. gen., n. sp., intranuclear within the hepatopancreatocytes
      of the European edible crab Cancer pagurus.
AB  - Only 1 genus (Nucleospora) within 1 family (Enterocytozoonidae) of the
      Microsporidia contains species that are parasitic within the nuclei of their host
      cells; to date, all described intranuclear Nucleospora spp. parasitise fish. This
      study describes the first intranuclear microsporidian parasite of an
      invertebrate, the European edible crab Cancer pagurus L. (Decapoda: Cancridae).
      Infected crabs displayed no obvious external signs, and maximum apparent
      prevalence of infection within a monthly sample was 3.45%. Infected
      hepatopancreatic tubules were characterised by varying numbers of hypertrophic
      and eosinophilic nuclei within epithelial cells. Parasite stages appeared as
      eosinophilic granular accumulations causing margination of host chromatin. In
      advanced cases, the tubule epithelia degenerated, with parasites and sloughed
      epithelial cells appearing in tubule lumens. All life stages of the parasite were
      observed within host nuclei. Uninucleate meronts were not detected, although
      binucleate stages were observed. Multinucleate plasmodia (sporogonal plasmodia)
      contained up to 22 nuclei in section, and late-stage plasmodia contained multiple
      copies of apparatus resembling the polar filament and anchoring disk, apparently
      associated with individual plasmodial nuclei. As such, aggregation and early
      assembly of sporoblast components took place within the intact sporogonial
      plasmodium, a feature unique to the Enterocytozoonidae. Liberation of sporoblasts
      from plasmodia or the presence of liberated sporoblasts was not observed in this
      study. However, large numbers of maturing and mature spores (measuring 1.3 +/-
      0.02 x 0.7 +/- 0.01 microm) were frequently observed in direct contact with the
      host nucleoplasm. Considering the shared features of this parasite with
      microsporidians of the family Enterocytozoonidae, and the unique presence of this
      parasite within the nucleoplasm of decapod crustacean hepatopancreatocytes, this
      parasite (Enterospora canceri) is proposed as the type species of a new genus
      (Enterospora) of microsporidian. Molecular taxonomic work is now required,
      comparing Enterospora to Enterocytozoon and Nucleospora, the 2 other genera
      within the Enterocytozoonidae.

PMID- 17523545
TI  - Enterospora sp., an intranuclear microsporidian infection of hermit crab
      Eupagurus bernhardus.
AB  - Recent work at our laboratory has led to the discovery of a new genus of
      microsporidian parasite residing in the family Enterocytozoonidae. The type
      species of this new genus, Enterospora canceri, is an intranuclear parasite
      infecting the hepatopancreatocytes of the decapod crustacean Cancer pagurus. Here
      we provide the second description of a parasite within the genus Enterospora,
      this time infecting the hermit crab Eupagurus bernhardus from U.K. waters. The
      pathological manifestation and ultrastructural features of the hermit crab
      parasite are very similar to those described for E. canceri. Further taxonomic
      comparisons based upon ultrastructural and molecular affinities of Enterospora
      are now required to define firmer links between this new genus within the
      Enterocytozoonidae and all other microsporidian families. The opportunistic
      nature of the discovery of a second intranuclear microsporidian within the
      Crustacea suggests that their presence may be more common than in higher animal
      groups.

PMID- 17523547
TI  - Kid tested, parent approved. Gates facility puts families first.

PMID- 17523546
TI  - Microarray analyses of gene expression in Japanese flounder Paralichthys
      olivaceus leucocytes during monogenean parasite Neoheterobothrium hirame
      infection.
AB  - In this study, the gene expression patterns of peripheral blood leucocytes (PBL)
      from Japanese flounder Paralichthys olivaceus were analyzed during the course of
      monogenean parasite Neoheterobothrium hirame infection in order to select
      candidates for molecular biomarkers of infection. cDNA microarray analysis was
      performed to compare the gene expression patterns of PBL between infected and non
      infected fishes. Among the 797 genes analyzed, 45 genes (5.6%) changed their
      expression levels. These genes included specific and non-specific immune-related
      genes (matrix metalloproteinase[MMP]-9, MMP-13, leukotriene B4 receptor, CD20
      receptor, MHC [major histocompatibility complex] Class I, MHC Class II beta
      chain, immunoglobulin light chain and immunoglobulin heavy chain). Significant up
      and down-regulation of some unknown genes was also observed. Several candidates
      for infection-marker genes were selected for further study. These genes included
      MMP-9, MMP-13, leukotriene b4 receptor, CD20 receptor, immunoglobulin heavy
      chain, immunoglobulin light chain and unknown genes coded as B613, E25, LB3(8),
      WE2(3), WE8-18R and WF12-18R.

PMID- 17523549
TI  - Finding furniture. Advice on selecting the right furnishings.

PMID- 17523548
TI  - Prescription for power. Advice on EP system reliability.

PMID- 17523550
TI  - Money well spent. A six-step approach to effective capital budgeting.

PMID- 17523551
TI  - Safety first: 'MR facility design guidelines' takes planners through the process.

PMID- 17523552
TI  - Under foot: A look at trends in hard floor care.

PMID- 17523553
TI  - Comment on "modeling of elastic nonlinearities in ferroelectric materials".
AB  - This letter discusses certain aspects in the modeling of nonlinear mechanical
      effects that were not correctly considered in a recent article in this journal.

PMID- 17523554
TI  - Stress-induced frequency shifts in rotated Y-cut langasite resonators with
      electrodes considered.
AB  - Stress-induced frequency shifts of the thickness-shear vibration of rotated Y-cut
      langasite resonators are studied with the electrode considered. The relationship
      between mass loading and force-frequency coefficients is explored for several
      kinds of electrode materials. Comparisons between Y-cut langasite and AT-cut
      quartz resonators are also presented.

PMID- 17523555
TI  - Piezoelectric properties in (K0.5Bi0.5)TiO3-(Na0.5Bi0.5)TiO3-BaTiO3 lead-free
      ceramics.
AB  - Lead-free piezoelectric ceramics with compositions around the morphotropic phase
      boundary (MPB) x(Na0.5Bi0.5)TiO3-y(K0.5Bi0.5)TiO3-zBaTiO3 [x + y + z = 1; y:z =
      2:1] were synthesized using conventional, solid-state processing. Dielectric
      maximum temperatures of 280 degrees C and 262 degrees C were found for tetragonal
      0.79(Na0.5Bi0.5)TiO3-0.14(K0.5Bi0.5)TiO3-0.07BaTiO3 (BNBK79) and MPB composition
      0.88(Na0.5Bi0.5)TiO3-0.08(K0.5Bi0.5)TiO3-0.04BaTiO3 (BNBK88), with depolarization
      temperatures of 224 degrees C and 162 degrees C, respectively. Piezoelectric
      coefficients d33 were found to be 135 pC/N and 170 pC/N for BNBK79 and BNBK88,
      and the piezoelectric d31 was determined to be -37 pC/N and -51 pC/N,
      demonstrating strong anisotropy. Coercive field values were found to be 37 kV/cm
      and 29 kV/cm for BNBK79 and BNBK88, respectively. The remanent polarization of
      BNBK88 (approximately 40 microC/cm2) was larger than that of BNBK79
      (approximately 29 microC/cm2). The piezoelectric, electromechanical, and high
      field strain behaviors also were studied as a function of temperature and
      discussed.

PMID- 17523556
TI  - Considerations on the measurement of the stability of oscillators with frequency
      counters.
AB  - The most common time-domain measure frequency stability, the Allan variance, is
      typically estimated using a frequency counter. Close examination the operation of
      modern high-resolution frequency counters shows that they do not make
      measurements in the commonly assumed. The consequence is that the results
      typically reported by many laboratories using these counters are not, in fact,
      the Allan variance, but a distorted representation. We elucidate the action of
      these counters by consideration of their operation in the Fourier domain, and
      demonstrate that the difference between the actual Allan variance and that
      delivered by these counters can very significant for some types of oscillators.
      We also discuss ways to avoid, or account for, a distorted estimation of Allan
      variance.

PMID- 17523557
TI  - The effect of AM noise on correlation phase-noise measurements.
AB  - We analyze the phase-noise measurement methods in which correlation and averaging
      is used to reject the background noise of the instrument. All the known methods
      make use of a mixer, used either as a saturated-phase detector or as a linear
      synchronous detector. Unifortunately, AM noise is taken in through the power-to
      dc-offset conversion mechanism that results from the mixer asymmetry. The
      measurement of some mixers indicates that the unwanted amplitude-to-voltage gain
      is of the order of 5-50 mV, which is 12-35 dB lower than the phase-to-voltage
      gain of the mixer. In addition, the trick of setting the mixer at a sweet point-
      off the quadrature condition--where the sensitivity to AM nulls, works only with
      microwave mixers. The HF-VHF mixers do not have this sweet point. Moreover, we
      prove that if the AM noise comes from the oscillator under test, it cannot be
      rejected by correlation. At least not with the schemes currently used. An example
      shows that at some critical frequencies the unwanted effect of AM noise is of the
      same order-if not greater--than the phase noise. Thus, experimental mistakes are
      around the corner.

PMID- 17523558
TI  - Acoustic droplet vaporization threshold: effects of pulse duration and contrast
      agent.
AB  - The use of superheated liquid perfluorocarbon droplets encased in albumin shells
      has been proposed as a minimally invasive alternative to current treatment of
      cancer by means of occlusion therapy. In response to an applied acoustic field,
      these droplets, which are small enough to pass through capillaries, vaporize into
      large gas bubbles that subsequently lodge in the vasculature. This technique,
      known as acoustic droplet vaporization (ADV) has been shown to successfully
      reduce blood flow in vivo, but for in situ conditions where attenuation is
      present, lower acoustic frequency and ADV threshold may be desirable. Thus, two
      methods to lower the ADV threshold at a lower 1.44 MHz were explored. The first
      part of this study investigated the role of pulse duration on ADV. The second
      part investigated the role of inertial cavitation (IC) external to a droplet by
      lowering the IC threshold in the host liquid with the presence of Definity
      contrast agent (CA). The threshold was found to be 5.5-5.9 MPa for short
      microsecond pulses and decreased for millisecond pulses (3.8-4.6 MPa). When CAs
      were present and long millisecond pulses were used, the ADV threshold decreased
      to values as low as 0.41 MPa.

PMID- 17523559
TI  - Binary code design for high-frequency ultrasound.
AB  - This paper proposes an approach to designing binary codes suitable for high
      frequency applications of coded excitation in medical ultrasound. For a high
      frequency ultrasound system, transmitting well-designed binary codes with a low
      sampling ratio (i.e., the bit rate divided by the transducer center frequency) is
      a practical way to improve the signal-to-noise ratio (SNR) because the challenge
      of implementing arbitrary-waveform generators for transmitting nonbinary codes
      increases with the frequency and the switching speed of square-wave pulsers are
      limited. One conventional approach designs codes using a base sequence that
      modulates wideband sequences up to the transducer passband. Because a major
      portion of codes is excluded as a candidate, codes designed using this approach
      typically need long compression filters for restoring the axial resolution, and
      they do not improve the SNR efficiently. In contrast, the approach proposed here
      searches all the codes that match the transducer passband; hence, the resultant
      codes exhibit better performance. The technique was tested using a bit rate of 50
      MHz and a sampling ratio of 2. For a transducer with an ideal Gaussian frequency
      response with a center frequency of 25 MHz and a -6 dB bandwidth of 15 MHz, the
      SNR for the same side-lobe extent was 1 to 6 dB higher for the codes designed
      using the proposed approach compared with those designed using the conventional
      approach. When a real transducer response with a center frequency of 26.4 MHz and
      a one-way -6 dB bandwidth of 20.7 MHz was considered, the codes designed using
      the proposed approach were superior by 0.5 to 5 dB. Therefore, our approach is
      better than the conventional approach for designing binary codes for high
      frequency ultrasound, with the results indicating that the moderate bit rate of
      50 MHz will suffice when the ultrasonic center frequency is 25 MHz.

PMID- 17523560
TI  - High-frequency ultrasound sensors using polymer microring resonators.
AB  - Polymer microring resonators are demonstrated as high-frequency, ultrasound
      detectors. An optical microring resonator consists of a ring waveguide closely
      coupled to a straight bus waveguide, serving as light input and output. Acoustic
      waves irradiating the ring induce strain, deforming the waveguide dimensions and
      changing the refractive index of the waveguide via the elasto-optic effect. These
      effects modify the effective refractive index of the guided mode inside the
      waveguide. The sharp wavelength dependence of the microring resonance can enhance
      the optical response to acoustic strain. Such polymer microring resonators are
      experimentally demonstrated in detecting broadband ultrasound pulses from a 50
      MHz transducer. Measured frequency response shows that these devices have
      potential in high-frequency, ultrasound detection. Design guidelines for polymer
      microring resonators forming an ultrasound detector array are discussed.

PMID- 17523561
TI  - Free-hand ultrasound scanning approaches for volume quantification of the mouse
      heart Left ventricle.
AB  - Two approaches for free-hand motion tracking that enable volumetric
      quantification of the murine heart were investigated. One approach used an
      instrumented, multijointed articulated arm attached to a 14 MHz ultrasound
      transducer array. A second approach used an E-beam transducer--a modified linear
      transducer array containing a main imaging array adjacent to three perpendicular
      tracking arrays. Motion between successive B-mode image frames was computed by
      tracking image speckle in each tracking array. Both tracking systems produced
      accurate results in a phantom validation study (4.50% error and 3.75% error for
      estimates derived using the articulated arm and E-beam tracking techniques,
      respectively). The tracking approaches also were tested in vivo on three mice.
      Results were compared to values obtained by mounting each mouse on a
      micromanipulator, adjusting its position by 0.5-mm increments, and acquiring B
      mode images using a high-resolution ultrasound scanner. Left ventricular end
      diastolic volume (LVEDV) estimates differed from values obtained using the high
      resolution scanner by a mean error of 18.2% and 2.60% for eight scans conducted
      on each of two mice using the articulated arm, and a mean error of 13.6%, 6.53%,
      and 12.58% for eight scans conducted on each of three mice using the E-beam.

PMID- 17523562
TI  - Intravascular photoacoustic imaging using an IVUS imaging catheter.
AB  - Catheter-based imaging of atherosclerosis with high resolution, albeit invasive,
      is extremely important for screening and characterization of vulnerable plaques.
      Currently, there is a need for an imaging technique capable of providing
      comprehensive morphological and functional information of plaques. In this paper,
      we present an intravascular photoacoustic imaging technique to characterize
      vulnerable plaques by using optical absorption contrast between normal tissue and
      atherosclerotic lesions. Specifically, we investigate the feasibility of
      obtaining intravascular photoacoustic (IVPA) images using a high-frequency
      intravascular ultrasound (IVUS) imaging catheter. Indeed, the combination of IVPA
      imaging with clinically available IVUS imaging may provide desired functional and
      morphological assessment of the plaque. The imaging studies were performed with
      tissue-mimicking arterial vessel phantoms and excised samples of rabbit artery.
      The results of our study suggest that catheter-based intravascular photoacoustic
      imaging is possible, and the combination of IVPA with IVUS has the potential to
      detect and differentiate atherosclerosis based on both the structure and
      composition of the plaque.

PMID- 17523563
TI  - Strain imaging using conventional and ultrafast ultrasound imaging: numerical
      analysis.
AB  - In elasticity imaging, the ultrasound frames acquired during tissue deformation
      are analyzed to estimate the internal displacements and strains. If the
      deformation rate is high, high-frame-rate imaging techniques are required to
      avoid the severe decorrelation between the neighboring ultrasound images. In
      these high-frame-rate techniques, however, the broader and less focused
      ultrasound beam is transmitted and, hence, the image quality is degraded. We
      quantitatively compared strain images obtained using conventional and ultrafast
      ultrasound imaging methods. The performance of the elasticity imaging was
      evaluated using custom-designed, numerical simulations. Our results demonstrate
      that signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial
      resolutions in displacement and strain images acquired using conventional and
      ultrafast ultrasound imaging are comparable. This study suggests that the high
      frame-rate ultrasound imaging can be reliably used in elasticity imaging if frame
      rate is critical.

PMID- 17523564
TI  - Challenges and implementation of radiation-force imaging with an intracardiac
      ultrasound transducer.
AB  - Intracardiac echocardiography (ICE) has been demonstrated to be an effective
      imaging modality for the guidance of several cardiac procedures, including
      radiofrequency ablation (RFA). However, assessing lesion size during the ablation
      with conventional ultrasound has been limited, as the associated changes within
      the B-mode images often are subtle. Acoustic radiation force impulse (ARFI)
      imaging is a promising modality to monitor RFAs as it is capable of visualizing
      variations in local stiffnesses within the myocardium. We demonstrate ARFI
      imaging with an intracardiac probe that creates higher quality images of the
      developing lesion. We evaluated the performance of an ICE probe with ARFI imaging
      in monitoring RFAs. The intracardiac probe was used to create high contrast, high
      resolution ARFI images of a tissue-mimicking phantom containing stiffer spherical
      inclusions. The probe also was used to examine an excised segment of an ovine
      right ventricle with a RFA-created surface lesion. Although the lesion was not
      visible in conventional B-mode images, the ARFI images were able to show the
      boundaries between the lesion and the surrounding tissue. ARFI imaging with an
      intracardiac probe then was used to monitor cardiac ablations in vivo. RFAs were
      performed within the right atrium of an ovine heart, and B-mode and ARFI imaging
      with the intracardiac probe was used to monitor the developing lesions. Although
      there was little indication of a developing lesion within the B-mode images, the
      corresponding ARFI images displayed regions around the ablation site that
      displaced less.

PMID- 17523565
TI  - SNR comparisons of beamforming strategies.
AB  - This paper defines the echo signal-to-noise ratio (eSNR) for pulse-echo systems
      that adapts to the effects of shift-varying impulse responses, spatiotemporal
      coding, and various beamformers. Measurement techniques using point targets or
      random scattering media can be interrelated for a broad range of experimental
      conditions through the eSNR. The eSNR definitions are also illustrated by
      comparing a spatial matched filter (SMF) beamformer to conventional dynamic
      receive focusing methods to evaluate performance based on resolution and
      sensitivity. Closed-form expressions are presented that predict eSNR gains from
      SMF approaches relative to other beamformers.

PMID- 17523566
TI  - Array signal processing for local arterial pulse wave velocity measurement using
      ultrasound.
AB  - A new signal processing approach to estimation of local arterial pulse wave
      velocity (PWV) in superficial arterial segments using long-axis ultrasound
      measurements is proposed. The method is designed to be resistant to estimation
      bias due to pulse wave reflections. It is evaluated using a laboratory test tank,
      and it appears to estimate local PWV with less bias than previously accepted
      methods, and with similar estimation variance to those methods.

PMID- 17523567
TI  - Characterization of changes in therapeutic ultrasound transducer performance over
      time using the angular spectrum method.
AB  - Strongly focused large aperture transducers used in high-intensity focused
      ultrasound treatments are prone to manufacturing defects and degradation. Current
      methods for evaluating transducer quality measure only bulk physical changes of
      transducers. We have determined the pressure distribution at the transducer
      surface, using the angular spectrum method, to detect defects of the transducer.
      Three therapeutic transducers were investigated. The pressure distribution at the
      focal plane of each transducer was measured and input into a back-projection
      algorithm to calculate the pressure distribution at the transducer surface. A
      number of scan window sizes were used for the pressure distribution measurement
      at the focal plane to determine the effect on the resolution of the calculated
      pressure distribution at the transducer surface. Results showed that one
      transducer might have suffered manufacturing defects. The second transducer
      degraded over 1 year of use with one half of the transducer suffering a partial
      loss of efficiency. The third transducer remained unchanged over 1 year. The scan
      window of 40 mm X 40 mm at the focal plane was required to identify defects 6 mm
      in diameter on the transducer surface. The results demonstrate that the angular
      spectrum method could be a useful tool for evaluating transducer quality.

PMID- 17523568
TI  - An ultrasonic time-delay spectrometry system employing digital processing.
AB  - Time-delay spectrometry (TDS) is a swept-frequency technique that has proven
      useful in several ultrasonic applications. Commercial TDS systems are available,
      but only in the audio frequency range. Several ultrasonic research TDS systems
      have been constructed, and they have been used effectively for substitution
      calibration of hydrophones and for measurement of attenuation and sound velocity
      in materials. Unfortunately these systems depend on features of commercial
      equipment no longer manufactured, so a new system has been designed using modern
      equipment and straightforward signal processing. This system requires a frequency
      source with a reasonably linear sweep of frequency versus time, audio frequency
      filters, a standard double-balanced mixer, a power splitter, a waveform digitizer
      capable of handling audio frequency signals, and a personal computer. An optional
      implementation that shifts the signal to a lower frequency for more convenient
      digitization and easier velocity measurements additionally requires an audio
      frequency oscillator and an audio-range analog multiplier. The processing steps
      are performed with standard signal processing software. To demonstrate the
      operation of the system, substitution calibration measurements of hydrophones as
      well as attenuation measurements on a tissue mimicking material were obtained and
      compared to a custom TDS system previously described by the authors. The data
      from these two TDS systems agree to within +/- 0.5 dB in the 1-10 MHz frequency
      range used. Higher frequency source transducers could be used to extend this
      range.

PMID- 17523569
TI  - A spline-based approach for computing spatial impulse responses.
AB  - Computer simulations are an essential tool for the design of phased-array
      ultrasonic imaging systems. FIELD II, which determines the two-way temporal
      response of a transducer at a point in space, is the current de facto standard
      for ultrasound simulation tools. However, the need often arises to obtain two-way
      spatial responses at a single point in time, a set of dimensions for which FIELD
      II is not well optimized. This paper describes an analytical approach for
      computing the two-way, far-field, spatial impulse response from rectangular
      transducer elements under arbitrary excitation. The described approach determines
      the response as the sum of polynomial functions, making computational
      implementation quite straightforward. The proposed algorithm, named DELFI, was
      implemented as a C routine under Matlab and results were compared to those
      obtained under similar conditions from the well-established FIELD II program.
      Under the specific conditions tested here, the proposed algorithm was
      approximately 142 times faster than FIELD II for computing spatial sensitivity
      functions with similar amounts of error. For temporal sensitivity functions with
      similar amounts of error, the proposed algorithm was about 1.7 times slower than
      FIELD II using rectangular elements and 19.2 times faster than FIELD II using
      triangular elements. DELFI is shown to be an attractive complement to FIELD II,
      especially when spatial responses are needed at a specific point in time.

PMID- 17523570
TI  - Acoustic characterization and prediction of the cut-off dimensionless frequency
      of an elastic tube by neural networks.
AB  - A neural network is developed to predict cut-off dimensionless frequencies of the
      antisymmetric circumferential waves (Ai) propagating around an elastic circular
      cylindrical shell of different radius ratio b/a (a, outer radius; b, inner
      radius). The useful data to train and test the performances of the model are
      determinated from calculated trajectories of natural modes of resonances or
      extracted from time-frequency representations of Wigner-Ville of the acoustic
      backscattered time signal obtained from a computation. In this work, the studied
      tubes are made of aluminum or stainless steel. The material density, the radius
      ratio b/a, the index i of the antisymmetric waves, and the propagation velocities
      in the tube, are selected like relevant entries of the model of neural network.
      During the development of the network, several configurations are evaluated. The
      optimal model selected is a network with two hidden layers. This model is able to
      predict the cut-off dimensionless frequencies with a mean relative error (MRE) of
      about 1%, a mean absolute error (MAE) of 3.10(-3) k1a, and a standard error (SE)
      of 10(-3) k1a (k1a is the dimensionless frequency, k is the wave number in
      water).

PMID- 17523571
TI  - Characterization of cMuts in rarefied gases.
AB  - The performance of capacitive micromachined ultrasonic transducers (cMUTs) was
      investigated at low pressures in various gases such as air, carbon dioxide, and
      helium. The aim was to replicate the pressure conditions likely to meet on the
      surface of other planets such as Mars, where ultrasonic wind velocity
      measurements might be possible. It is demonstrated that cMUTs are capable of
      operating at low pressures, and the response to pressures below terrestrial
      atmospheric values is observed experimentally and compared to theoretical
      predictions. The center frequency of operation and sensitivity are both observed
      to be affected by changing pressures.

PMID- 17523572
TI  - Wavenumber domain analysis of two-dimensional SAW images captured by phase
      sensitive laser probe system.
AB  - This paper is aimed at demonstrating how the wavenumber domain analysis of two
      dimensional (2-D) images captured by phase-sensitive laser probe systems is
      applied in the characterization of RF SAW devices. Effectiveness is demonstrated
      through the selective characterization of spurious resonance modes and scattered,
      nonguided modes appearing in SAW resonators.

PMID- 17523573
TI  - A fractional filter-based beamformer architecture using postfiltering approach to
      minimize hardware complexity.
AB  - A novel beamformer architecture using fractional delay filters is proposed and
      verified through experiments. By performing interchannel summation prior to
      filtering operation in the manner producing no error, the proposed architecture
      requires only three four-tap filters for the whole beamformer and four simple
      demultiplexers per each channel.

PMID- 17523574
TI  - "Bench to bedside"--transitions in nursing research.

PMID- 17523575
TI  - Day surgery and recovery in women with a suspicious breast lesion: evaluation of
      a psychoeducational nursing intervention.
AB  - The study assessed whether a nursing intervention based on self-regulation
      theory, the Attentional Focus and Symptom Management Intervention (AFSMI), could
      help women who underwent day surgery for breast cancer to achieve better pain
      management and decreased emotional distress. The sample consisted of 117 patients
      with breast cancer who were outpatients and undergoing surgery as part of the
      initial treatment for their cancer. All subjects were interviewed at three
      different occasions. The subjects were randomized into the experimental group (n
      = 61) or the usual care group (control, n = 56). The subjects in the experimental
      group received the intervention in two sessions, 3-4 days and 10-11 days after
      surgery. The outcomes were the subjects' pain and emotional distress. Results
      showed significant differences between the experimental and control group at post
      test on home management, total mood disturbance, confusion and tension scores
      implying that the intervention was effective in achieving these outcomes.
      Clinical significance has illustrated that a nursing intervention applied during
      immediate recovery of breast cancer surgery is quite clinically relevant to
      reduce emotional distress. Self-regulation theory could effectively be used as a
      guide in developing nursing intervention programs in practice for patients with
      cancer undergoing day surgery as a primary treatment.

PMID- 17523576
TI  - Getting results for hematology patients through access to the electronic health
      record.
AB  - PURPOSE: To conduct a needs assessment to identify patient and provider
      perceptions about providing patients with access to their electronic health
      record in order to develop an online system that is appropriate for all
      stakeholders. METHODS: Malignant hematology patients were surveyed and health
      care providers were interviewed to identify issues and validate concerns reported
      in the literature. Based on the analysed data, a prototype will be designed to
      examine the feasibility and efficacy of providing patients with access to their
      electronic health record and tailored information. RESULTS: 61% of patients
      reported using the internet to find health information; 89% were interested in
      accessing their electronic health record and 79% stated they would benefit from
      educational material along with the results. Staff members viewed patient online
      access to the record favourably, but expressed the importance of providing the
      necessary patient support and education. A Web-based prototype was developed for
      patients to review their registration data and blood results. CONCLUSIONS:
      Hematology oncology patients are more interested in using the internet to monitor
      their clinical information than to find health information. Using the constructed
      prototype, the feasibility of this project is currently being tested.

PMID- 17523577
TI  - Living with lymphedema: a qualitative study of women's perspectives on prevention
      and management following breast cancer-related treatment.
AB  - A phenomenological research method was used to investigate the experience of
      lymphedema in 13 women following breast cancer-related treatment. The women,
      ranging in age from 45 to 82, living on the east coast of Canada, had lymphedema
      of the upper extremity for at least one year, and had no evidence of active
      cancer disease. Semi-structured interviews were used to examine the physical and
      psychosocial suffering that women with lymphedema experienced. The lack of
      appropriate pre-intervention education and post-intervention support by health
      care professionals as well as the lack of effective protocols to prevent
      lymphedema combined to intensify the suffering. Data analysis incorporated van
      Manen's (1990) six research activities which give human science its vigor. These
      non-sequential steps assisted in identifying five major themes: 1) Constancy; 2)
      Yearning for Normalcy; 3) Continually Searching; 4) Emotional Impact; and 5)
      Abandonment. The prevailing thread or essence salient to all five themes in this
      study is denoted as Existential Aloneness as each participant expressed a sense
      of isolation, of being on their own, of being set adrift to discover what they
      could about lymphedema, in the best way that they could. Nursing implications and
      recommendations for change are highlighted.

PMID- 17523578
TI  - Leaving our imprints: an exploration into the nurse-patient relationship.
AB  - Oncology nursing aims to promote physical and psychosocial well-being of
      individuals and families at risk for, or living with, a life-threatening illness.
      A basic component of nursing practice is the nurse-patient relationship (Canadian
      Nurses Association, 2002). This relationship has been shown to have a positive
      impact on individuals' well-being as they journey through their cancer experience
      (Herth, 1995). While the nurse-patient therapeutic relationship is fundamental to
      nursing care and may be quite subtle in its transaction, it is a complex
      phenomenon with every encounter being meaningful and impacting both the patient
      and the nurse. Reflecting on the nature of this relationship can facilitate a
      richer and deeper awareness of the unique contribution oncology nurses make in
      the lives they touch and are touched by. This presentation will explore the
      therapeutic nurse-patient relationship in oncology nursing. The authors intend to
      facilitate self-reflection and increased awareness of both the art and science of
      the therapeutic relationship. In particular, qualities of the nurse-patient
      relationship, the importance of communication, both verbal and nonverbal, and the
      use of silence will be explored. We will incorporate theory, evidence,
      experiential learning along with story-telling, music, poetry and video images to
      convey our message.

PMID- 17523579
TI  - Lesley Degner, RN, PhD.

PMID- 17523580
TI  - Characteristics and behaviors of ketamine users in France in 2003.
AB  - The increase in recreational use of ketamine in France led to the carrying out of
      a survey aimed at depicting the sociological profiles of French ketamine users,
      their addictive behaviors, and the characteristics relevant to the use of the
      substance. This survey is based upon the analysis of 250 questionnaires, 24 semi
      directive interviews, and two focus groups. Data was collected between July 2002
      and June 2003 among individuals who had used ketamine at least once since January
      1, 2001. The respondents were mostly males with a polydrug addiction, aged about
      24, with little post-secondary education and no steady job. Ketamine was
      generally the last substance experimented with throughout their lifetime, as of
      the age of 22. The article reviews the frequency of ketamine use observed in the
      population surveyed, as well as the routes of administration, the quantities
      used, the circumstances of use, the sought-after effects and those experienced,
      and the risks perceived by the users themselves. The data collected provides
      working facts to allow for the development and implementation of policies for
      preventing the use and abuse of ketamine among vulnerable populations.

PMID- 17523581
TI  - Single versus repeated sessions of ketamine-assisted psychotherapy for people
      with heroin dependence.
AB  - A prior study found that one ketamine-assisted psychotherapy session was
      significantly more effective than active placebo in promoting abstinence
      (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated
      sessions of ketamine-assisted psychotherapy in promoting abstinence in people
      with heroin dependence, 59 detoxified inpatients with heroin dependence received
      a ketamine-assisted psychotherapy (KPT) session prior to their discharge from an
      addiction treatment hospital, and were then randomized into two treatment groups.
      Participants in the first group received two addiction counseling sessions
      followed by two KPT sessions, with sessions scheduled on a monthly interval
      (multiple KPT group). Participants in the second group received two addiction
      counseling sessions on a monthly interval, but no additional ketamine therapy
      sessions (single KPT group). At one-year follow-up, survival analysis
      demonstrated a significantly higher rate of abstinence in the multiple KPT group.
      Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent,
      compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No
      differences between groups were found in depression, anxiety, craving for heroin,
      or their understanding of the meaning of their lives. It was concluded that three
      sessions of ketamine-assisted psychotherapy are more effective than a single
      session for the treatment of heroin addiction.

PMID- 17523582
TI  - Patterns of ketamine use among young injection drug users.
AB  - Ketamine is a dissociative anesthetic that has emerged as an increasingly popular
      choice among young drug users. Recent research indicates the presence of hidden
      populations of young people who inject ketamine in New York and other U.S.
      cities. Applying an ethno-epidemiological approach, the authors recruited 40
      young injection drug users (IDUs) (< 25 years old) in New York City to explore
      health risks associated with ketamine use. This analysis looks at the varying
      patterns and frequencies of ketamine injection by examining personal, social, and
      cultural aspects of these young people's lives. We learned that drug-using
      histories, experiential dimensions, sociocultural characteristics, and
      associations with other young people help account for the different patterns of
      injecting ketamine within the sample. In particular, these findings indicate that
      young people who were more frequent ketamine injectors had the following
      characteristics: initiated injection drug use with ketamine; enjoyed the effects
      of ketamine, were stably housed; lived in the vicinity of New York City; and
      associated with others who also injected ketamine.

PMID- 17523583
TI  - Is recreational ecstasy (MDMA) use associated with higher levels of depressive
      symptoms?
AB  - Due to potential serotonergic deficits, 3,4-methylenedioxymethamphetamine (MDMA
      or Ecstasy) may cause long-term mood disruptions in recreational Ecstasy users.
      The purpose of this review is to evaluate the evidence for a relationship between
      recreational Ecstasy use and higher levels of depressive symptoms. Eleven out of
      22 studies initially have reported significantly higher depression scores in
      Ecstasy users in comparison to control participants. However, only three studies
      ultimately have revealed significantly higher depression scores in comparison to
      cannabis or polydrug controls. Furthermore, most studies have suffered from
      methodological weaknesses, and the levels of depressive symptoms that have been
      found in Ecstasy users have not been shown to be much higher than those found in
      normative groups. The evidence for an association specifically between Ecstasy
      use and higher levels of depressive symptoms is currently unconvincing, but the
      frequent concomitant use of Ecstasy and other illicit drugs has been shown to be
      associated with higher levels of depressive symptoms. Possible causes include
      polydrug use in general, MDMA-induced serotonergic deficits, individual effects
      of illicit drugs besides Ecstasy, combined effects of MDMA and other illicit
      drugs, and preexisting differences in the levels of depressive symptoms in
      Ecstasy users.

PMID- 17523584
TI  - Spiritual/Religious experiences and in-treatment outcome in an inner-city program
      for heroin and cocaine dependence.
AB  - Although spirituality is an integral component of some of the most popular
      approaches to substance abuse treatment, there is little empirical evidence for a
      causal relationship between spirituality and treatment success. In the present
      study, 169 (121 male) opiate- or cocaine-abusing treatment seekers completed the
      Index of Spiritual Experience (INSPIRIT), a questionnaire that assesses both
      spirituality and religiosity. Responses were analyzed in terms of demographic
      variables and in-treatment outcome, which was determined by treatment retention
      and drug screens from observed biweekly urine collections. Religious/spiritual
      beliefs were common in these participants and were associated with in-treatment
      outcome: total INSPIRIT score was weakly correlated (r = .16, p < .04) with
      number of subsequent cocaine-negative urines, and participants reporting that
      they frequently spent time on religious/spiritual activities showed significantly
      better outcomes in terms of subsequent drug use and treatment retention. Women
      and African Americans were more likely than men and non-African Americans to
      report religious and spiritual beliefs or experiences on several individual
      items, and African Americans had higher INSPIRIT scores than Caucasians. The
      results suggest that spiritual and religious experience plays a role in substance
      abuse recovery and that demographic characteristics should be considered in the
      design of spiritually oriented behavioral interventions for addiction.

PMID- 17523585
TI  - Reclaiming futures: communities helping teens overcome drugs, alcohol and crime-
      a new practice framework for juvenile justice.
AB  - Increasing numbers of youth entering the juvenile justice system on drug-related
      charges require new practice frameworks for youth advocates. Screening,
      assessment and intervention capabilities have not kept pace with the youth who
      need them. This article presents an overview of a new approach, based on the
      system of care movement, to integrated care service provision for this
      population. Utilizing the Reclaiming Futures initiative--being piloted in 10
      communities in the United States--as a model for change, the article suggests
      that juvenile justice, in partnership with treatment and other community
      stakeholders, can have a positive impact on this social problem.

PMID- 17523586
TI  - Client outcomes from rural substance abuse treatment.
AB  - Several national evaluations have been conducted since the late 1960s that have
      assessed the effectiveness of publicly-funded substance abuse treatment in the
      United States. These studies, however, have focused principally on urban-based
      treatment programs, and it is unclear whether findings from urban programs can be
      replicated in outcome studies of programs in rural areas. The current study,
      therefore, examined the treatment outcomes of clients admitted to one of several
      short-term inpatient or outpatient drug-free treatment agencies in rural
      Kentucky. Findings showed that treatment was associated with reductions in drug
      use and criminality during a six-month follow-up interval. Employment status also
      improved significantly, and health services utilization was reduced. The
      similarity between the current findings and findings from national outcome
      studies of urban-based treatment programs is discussed.

PMID- 17523587
TI  - Why the concept-based therapeutic community can no longer be called drug-free.
AB  - In the last two decades, a complex controversy has emerged in therapeutic
      community (TC) drug treatment programs, many of which are experiencing a marked
      increase in addicted clients with co-existing mental health disorders. This
      situation calls into question many theoretical and practical aspects of the TC
      approach to addiction recovery. Among the central issues: use of psychotropic
      medications for the increasing cases of comorbidity among substance abuse clients
      entering the TC, the influx of mental health professionals, and employment of a
      growing number of mental health interventions or services. The traditional drug
      free self-help approach to drug treatment by the TC (with its own set of
      treatment interventions) and its historic dominance by ex-addicts or recovering
      persons as key staff are undergoing change. Integrating a biopsychosocial model
      into the traditional TC treatment modality requires a variety of adjustments that
      challenge the status quo in these programs. In particular, the use of
      psychotropic medications and mental health service providers in TC programs has
      improved the delivery of treatment to clients but at the same time it has created
      a cultural conflict for paraprofessional staff espousing the drug-free self-help
      philosophy. The clinical implications and organizational challenges of this
      predicament are described. Recommendations are provided on how to accept current
      health care realities without compromising the unique qualities of the TC
      approach.

PMID- 17523588
TI  - Effectiveness of different models of case management for substance-abusing
      populations.
AB  - Case management has been implemented in substance abuse treatment to improve
      (cost-) effectiveness, but controversy exists about its potential to realize this
      objective. A systematic and comprehensive review of peer-reviewed articles (n =
      48) published between 1993 and 2003 is presented, focusing on the effects of
      different models of case management among various substance-abusing populations.
      Results show that several studies have reported positive effects, but only some
      randomized and controlled trials have demonstrated the effectiveness of case
      management compared with other interventions. Longitudinal effects of this
      intervention remain unclear. Although no compelling evidence was found for the
      effectiveness of case management, some evidence is available about the
      (differential) effectiveness of intensive case management and assertive community
      treatment for homeless and dually-diagnosed substance abusers. Strengths-based
      and generalist case management have proven to be relatively effective for
      substance abusers in general. Most positive effects concern reduced use of
      inpatient services and increased utilization of community-based services,
      prolonged treatment retention, improved quality of life, and high client
      satisfaction. Outcomes concerning drug use and psychosocial functioning are less
      consistent, but seem to be mediated by retention in treatment and case
      management. Further research is required to learn more about the extent of the
      effects of this intervention, how long these are sustained and what specific
      elements cause particular outcomes.

PMID- 17523589
TI  - Codeine cough syrup use among African-American crack cocaine users.
AB  - While studies show evidence of a clear problem with the prevalence of crack
      cocaine and codeine cough syrup use separately, the relationship between these
      substances of abuse and concurrent polydrug use is unknown. In an attempt to
      ascertain beyond anecdotal evidence, the authors carried out a cross-sectional
      study among 482 African-American crack users to investigate the differences
      between those who were concurrently codeine cough syrup users and those who were
      not codeine cough syrup users in Houston, Texas. Logistic regression indicated
      that codeine use was significantly associated with lower participant age and
      lower education; codeine cough syrup users were significantly more likely than
      nonusers to not have a main sexual partner. In addition, codeine users had
      significantly higher odds of ever trading sex for money, marijuana use, and fry
      use. These findings are important in determining the "cultural novelties"
      relative to crack and codeine use among younger African Americans.

PMID- 17523590
TI  - Interweaving anion templation.
AB  - A new general interweaving anion templation strategy for the formation of
      interpenetrated and interlocked architectures is presented. Furthermore, the
      functional properties of the resulting systems, which have novel anion binding
      and sensory properties, are discussed.

PMID- 17523591
TI  - Optimizing TiO2-based phosphopeptide enrichment for automated multidimensional
      liquid chromatography coupled to tandem mass spectrometry.
AB  - An automated online multidimensional liquid chromatography system coupled to ESI
      based tandem mass spectrometry was used to assess the effectiveness of TiO2 in
      the enrichment of phosphopeptides from tryptic digests of protein mixtures. By
      monitoring the enrichment of phosphopeptides, an optimized set of loading, wash,
      and elution conditions were realized for TiO2. A comparison of TiO2 with other
      resins used for phosphopeptide enrichment, Fe(III)-IMAC and ZrO2, was also
      carried out using tryptic digests of both simple and moderately complex protein
      mixtures; where TiO2 was shown to be superior in performance.

PMID- 17523592
TI  - Analysis of adenosine triphosphate and glutathione through gold nanoparticles
      assisted laser desorption/ionization mass spectrometry.
AB  - This paper describes the use of aptamer-modified gold nanoparticles (Apt-AuNPs)
      as selective probes and AuNPs as the surface-assisted laser desorption/ionization
      (SALDI) matrixes for the determination of adenosine triphosphate (ATP) by mass
      spectrometry (MS). The aptamers were covalently attached to the surface of AuNPs
      to form Apt-AuNPs that provided selectivity toward ATP. However, Apt-AuNPs are
      less efficient laser desorption/ionization (LDI) matrixes when compared to AuNPs.
      By using Apt-AuNPs as selective probes and AuNPs as LDI matrixes, the MS approach
      provided the limit of detection (LOD) for ATP at a signal-to-noise ratio of 3 of
      0.48 microM. When compared to conventional organic matrixes (e.g., 2,5
      dihydroxybenzoic acid), AuNPs as LDI matrixes provide a number of advantages,
      including ease of preparation, selectivity, sensitivity, and repeatability.
      Sequential analysis of ATP and GSH in human cell lysates by SALDI with negative
      and positive MS modes, respectively, using Apt-AuNPs and AuNPs has been
      demonstrated. The present results demonstrate the practicality of the approach
      for monitoring the bioactivity of cells through determinations of the
      concentrations of ATP and GSH.

PMID- 17523593
TI  - Model of vapor-induced resistivity changes in gold-thiolate monolayer-protected
      nanoparticle sensor films.
AB  - An investigation of the modulation of charge transport through thin films of n
      octanethiolate monolayer-protected gold nanoparticles (MPN) induced by the
      sorption of organic vapors is presented. A model is derived that allows
      predictions of MPN-coated chemiresistor (CR) responses from vapor-film partition
      coefficients, and analyte densities and dielectric constants. Calibrations with
      vapors of 28 compounds collected from an array of CRs and a parallel thickness
      shear-mode resonator are used to verify assumptions inherent in the model and to
      assess its performance. Results afford insights into the nature of the vapor-MPN
      interactions, including systematic variations in apparent film swelling
      efficiencies, and show that the model can predict CR responses typically to
      within 24%. Using CRs of different dimensions, vapor sensitivities are found to
      be virtually independent of the MPN film volume over a range of 104 (device-area
      x MPN layer thickness). Sensitivities vary inversely with analyte vapor pressure
      similarly for the two sensor types, but the CR sensor affords significantly
      greater signal-to-noise ratios, yielding calculated detection limits in the low
      part-per-billion concentration range for several of the analytes tested. The
      implications of these results for implementing MPN-coated CR arrays as detectors
      in microanalytical systems are considered.

PMID- 17523594
TI  - Label-free detection of bacteria by electrochemical impedance spectroscopy:
      comparison to surface plasmon resonance.
AB  - The low but known risk of bacterial contamination has emerged as the greatest
      residual threat of transfusion-transmitted diseases. Label-free detection of a
      bacterial model, Escherichia coli, is performed using nonfaradic electrochemical
      impedance spectroscopy (EIS). Biotinylated polyclonal anti-E. coli is linked to a
      mixed self-assembled monolayer (SAM) on a gold electrode through a strong biotin
      neutravidin interaction. The binding of one antibody molecule for 3.6 neutravidin
      molecules is determined using the surface plasmon resonance (SPR). The detection
      limit of E. coli found by SPR is 10(7) cfu/mL. After modeling the impedance
      Nyquist plot of E. coli/anti-E. coli/mixed SAM/gold electrode for increasing
      concentrations of E. coli (whole bacteria or lysed bacteria), the main parameter
      that is modified is the polarization resistance RP. A sigmoid variation of RP is
      observed when the log concentration of bacteria (whole or lysed) increases. A
      concentration of 10 cfu/mL whole bacteria is detected by EIS measurements while
      103 cfu/mL is detected for lysed E. coli.

PMID- 17523595
TI  - Quantification of intracellular phosphorylated carbohydrates in HT29 human colon
      adenocarcinoma cell line using liquid chromatography-electrospray ionization
      tandem mass spectrometry.
AB  - The quantitative understanding of the role of sugar phosphates in regulating
      tumor energetic metabolism at the proteomic and genomic level is a prerequisite
      for an efficient rational design in combined drug chemotherapy. Therefore, it is
      necessary to determine accurately the concentration of the main sugar phosphate
      pools at the lower concentrations present in the often-limited volume of tumor
      cell samples. Taking as an example the human adenocarcinoma cell line HT29, we
      here report a fast and reliable quantitative method based on the use of liquid
      nitrogen, a weak acid extraction, and liquid chromatography-electrospray
      ionization tandem mass spectrometry to quantify simultaneously the intracellular
      concentration of sugar phosphate pools. The method was set up using standard
      addition curves. Thus, it is possible to identify and quantify hexose phosphate,
      pentose phosphate, and triose phosphate pools up to 0.02-0.10 ng x microL(-1),
      depending on the analyte. The method developed was here used for the quantitative
      study of changes in phosphorylated carbohydrates of central carbon metabolism
      when high or low glucose concentration conditions are induced in vitro in the
      HT29 human colon adenocarcinoma cell line.

PMID- 17523596
TI  - Separation of microparticles and biological cells inside an evaporating droplet
      using dielectrophoresis.
AB  - Microparticles or biological cells mixed in water were separated using the
      combination of an electrical force due to dielectrophoresis and a mechanical one
      generated in an evaporating droplet. Micropatterned electrodes of Au were
      fabricated on the silicon dioxide layer and were used to generate
      dielectrophoresis. Polystyrene particles, red blood cells. and E. coli were used
      as separating objects. Microparticles and biological cells were separated by
      adjusting the amplitude and frequency of the applied voltage. Although the
      mechanical force was enough to transport the particles to the boundary of the
      droplet, nevertheless, it could not detach the particles trapped at the
      electrode. Based on this work, the microparticles and biological cells can be
      separated, controlled, and sensed without using a liquid pumping unit.

PMID- 17523597
TI  - Analysis of chiral amino acids in conventional and transgenic maize.
AB  - In this work, a new chiral micellar electrokinetic chromatography with laser
      induced fluorescence detection (chiral-MEKC-LIF) method is proposed to identify
      and quantify D- and L-amino acids in three lines of transgenic maize and their
      corresponding nontransgenic parental lines grown under identical conditions. The
      optimized procedure includes amino acids extraction, derivatization with FITC and
      chiral-MEKC-LIF separation in a background electrolyte composed of 100 mM sodium
      tetraborate, 80 mM SDS, and 20 mM beta-CD at pH 10.0. The D- and L-forms of Arg,
      Ser, Ala, Glu, and Asp, corresponding to the majority amino acids usually found
      in maize, are separated in less than 25 min with efficiencies up to 890,000
      plates/m and high sensitivity (i.e., LODs as low as 160 nM were obtained for D
      Arg for a signal-to-noise ratio of three), allowing the detection of 1% D-Arg in
      the presence of 99% of its opposite enantiomer. Using this method, different D
      amino acids are detected in all investigated maize samples providing the
      reproducible quantification of the D-enantiomeric excess (% d-aa) for each amino
      acid calculated as % D-aa = 100D-aa/(D-aa + L-aa). Thus, significant differences
      were observed among the % d-aa values for the different conventional varieties
      (Aristis, Tietar, and PR33P66 maize) as could be expected from their natural
      variability. More interestingly, comparing each conventional maize with its
      corresponding transgenic line, very similar % D-aa values were obtained for one
      of the studied maize couples (Tietar vs Tietar-Bt) what could be presented as a
      new proof of their substantial equivalence. However, significant differences in
      the % d-aa values were observed for the other lines of maize studied. It is
      concluded that enantioselective procedures can open new perspectives in the study
      of transgenic organisms in order to corroborate (or not) the equivalence with
      their conventional counterparts.

PMID- 17523598
TI  - Possibility of an antiparallel (tetramer) quadruplex exhibited by the double
      repeat of the human telomere.
AB  - Under physiological concentrations of Na+ and K+, human telomeric DNA can self
      associate into G-quadruplexes. On the basis of circular dichroism, gel
      electrophoresis, gel filtration, and UV-melting experiments, we report here that
      the double repeat of human telomere (d-TTAGGGTTAGGG; HUM2) forms parallel as well
      as antiparallel quadruplexes in the presence of K+, whereas Na+ facilitates only
      the antiparallel form. Here, the gel techniques and CD studies have proved to be
      complementary in detecting the molecularity and pattern of strand orientation. By
      correlating the gel and CD experiments, the antiparallel G-quadruplex was
      identified as a tetrameric species, whereas the parallel G-quadruplex was found
      to be dimeric. Both structural species were separated through gel filtration,
      which when run on native polyacrylamide gel electrphoresis (PAGE), confirmed
      their molecularity. UV-melting profiles also confirm the presence of two biphasic
      and one monophasic structural species in the presence of K+ and Na+,
      respectively. Though our observation is consistent with the recent NMR report
      (Phan, A. T., and Patel, D. J. (2003) J. Am. Chem. Soc. 125, 15021-15027), it
      seems to differ in terms of the molecularity of the antiparallel quadruplex. A
      model is proposed for an antiparallel tetrameric quadruplex, showing the
      possibility of Watson-Crick hydrogen bonds between intervening bases on
      antiparallel strands. This article expands the known structural motifs of DNA
      quadruplexes. To the best of our knowledge, four-stranded antiparallel
      quadruplexes have not been characterized to date. On the basis of the model, we
      hypothesize a possible mechanism for telomere-telomere association involving
      their G-overhangs, during certain stages of the cell cycle. The knowledge of
      peculiar geometries of the G-quadruplexes may also have implications for its
      specific recognition by ligands.

PMID- 17523599
TI  - Glucagon amyloid-like fibril morphology is selected via morphology-dependent
      growth inhibition.
AB  - The 29-residue peptide hormone glucagon readily fibrillates at low pH, but the
      structure and morphology of the fibrils are very sensitive to the environmental
      conditions. Here we have investigated the mechanism behind the differences in
      morphology observed when glucagon fibrils are formed at different peptide
      concentrations. Electron microscopy shows that fibrils formed at low glucagon
      concentration (0.25 mg/mL) are twisted, while fibrils formed at high
      concentration (8 mg/mL) are straight. Monitoring the fibrillation kinetics at
      different concentrations, we find that the lag time has an unexpected maximum at
      a concentration of 1 mg/mL, with faster fibrillation at both lower and higher
      concentrations. Seeding experiments show that small amounts of straight fibril
      seeds can accelerate fibril growth at both low and high glucagon concentration,
      while twisted fibril seeds cannot grow at high concentrations. We conclude that
      there exists a morphology-dependent mechanism for inhibition of glucagon fibril
      growth. Light scattering experiments indicate that glucagon is mainly monomeric
      below 1 mg/mL and increasingly trimeric above this concentration. We propose that
      the glucagon trimer is able to specifically inhibit growth of the twisted fibril
      morphology. Such inhibitory binding of molecules in an unproductive conformation
      could also play a role in the selection of morphologies for other fibril-forming
      peptides and proteins.

PMID- 17523600
TI  - Long-range structural and dynamical changes induced by cofactor binding in DNA
      methyltransferase M.HhaI.
AB  - The bacterial DNA cytosine methyltransferase M.HhaI sequence-specifically
      modifies DNA in an S-adenosylmethionine dependent reaction. The enzyme stabilizes
      the target cytosine (GCGC) into an extrahelical position, with a concomitant
      large movement of an active site loop involving residues 80-99. We used
      multidimensional, transverse relaxation-optimized NMR experiments to assign
      nearly 80% of all residues in the cofactor-bound enzyme form, providing a basis
      for detailed structural and dynamical characterization. We examined details of
      the previously unknown effects of the cofactor binding with M.HhaI in solution.
      Addition of the cofactor results in numerous structural changes throughout the
      protein, including those decorating the cofactor binding site, and distal
      residues more than 30 A away. The active site loop is involved in motions both on
      a picosecond to nanosecond time scale and on a microsecond to millisecond time
      scale and is not significantly affected by cofactor binding except for a few N
      terminal residues. The cofactor also affects residues near the DNA binding cleft,
      suggesting a role for the cofactor in regulating DNA interactions. The allosteric
      properties we observed appear to be closely related to the significant amount of
      dynamics and dynamical changes in response to ligand binding detected in the
      protein.

PMID- 17523601
TI  - Two-dimensional circularly polarized IR photon echo spectroscopy of polypeptides:
      four-wave-mixing optical activity measurement.
AB  - A coherent two-dimensional (2D) optical spectroscopy utilizing circularly
      polarized (CP) beams, which was shown to be useful in studying molecular
      chirality in condensed phases, was theoretically proposed recently [Cho et al. J.
      Chem. Phys. 2003, 119, 7003]. A photon echo (PE) version of 2D optical activity
      spectroscopy is discussed in this paper. Considering various dipeptide and
      polypeptide systems, where the amide I local modes constitute the set of basis
      modes used to describe exciton and biexciton states as linear combinations of
      those basis modes, we present numerically simulated 2D circularly polarized IR PE
      spectra. It is shown that this novel spectroscopic method can provide additional
      information on the angles between the transition magnetic dipole and the
      transition electric dipole of two different vibrationally excited states, which
      are highly sensitive to the 3D structure and chirality of a given polypeptide.
      Also, a hierarchical relation of IR absorption, vibrational circular dichroism,
      2D IR PE, and 2D CP-IR PE is discussed to show advantages of 2D optical activity
      spectroscopy in general.

PMID- 17523602
TI  - Dynamics of clusters initiated by photon and surface impact.
AB  - Clusters of atoms/molecules show dynamics characteristic of the method of
      excitation. Two contrasted processes are discussed: (1) electronic excitation via
      single-photon absorption and (2) impulsive excitation of nuclear motions by
      surface impact. Process 1 is exemplified by photodissociation dynamics of size
      selected metal cluster ions. The electronic energy is converted most likely to
      vibrational energy of internal modes; dissociation follows via statistical
      mechanism to produce energetically favored fragments. Exceptionally, a silver
      cluster ion, Ag4(+), is shown to undergo nonstatistical dissociation along the
      potential-energy surface of the excited state. Energy partitioning to
      translational and vibrational modes of fragments is analyzed as well as bond
      dissociation energies. Furthermore, the spectrum of the photodissociation yield
      provides electronic and geometrical structures of a cluster with the aid of ab
      initio calculations; manganese, Mn(N)(+), and chromium, Cr(N)(+), cluster ions
      are discussed, where the importance of magnetic interactions is manifested. On
      the other hand, momentum transfer upon surface impact plays a role in process 2.
      An impulsive mechanical force triggers extraordinary chemical processes distinct
      from those initiated by atomic collision as well as photoexcitation. Experiments
      on aluminum, Al(N)(-), silicon, SiN(-), and solvated, I(2)(-)(CO2)(N), cluster
      anions provide evidence for reactions proceeding under extremely high
      temperatures, such as pickup of surface atoms, annealing of products, and
      mechanical splitting of chemical bonds. In addition, a model experiment to
      visualize and time-resolve the cluster impact process is performed by using a
      micrometer-sized liquid droplet. Multiphoton absorption initiates superheating of
      the droplet surface followed by a shock wave and disintegration into a number of
      small fragments (shattering). These studies further reveal how the nature of
      chemical bonds influences the dynamics of clusters.

PMID- 17523603
TI  - Hydrogen-bonding between pyrimidine and water: a vibrational spectroscopic
      analysis.
AB  - We present an experimental and a theoretical study on hydrogen-bonding between
      pyrimidine and water as the H-donor. The degree of hydrogen-bonding in this
      binary system varies with mixture composition. This was monitored experimentally
      by polarization-resolved linear Raman spectroscopy with the pyrimidine ring
      breathing mode nu1 as a marker band. A subsequent quantitative line shape
      analysis of the isotropic Raman intensity for 24 pyrimidine/water mixtures
      clearly revealed a splitting into three spectral components upon dilution with
      water. The two additional peaks have been assigned to distinct groups of hydrogen
      bonded species that differ in the number of pyrimidine nitrogen atoms (N)
      involved in hydrogen-bonding to water hydrogen atoms (H). From the integrated
      Raman intensities for "free" and "hydrogen-bonded" pyrimidine, a concentration
      profile for these species was established. Our assignments and interpretations
      are supported by quantum mechanical calculations of structures and by vibrational
      spectra for pyrimidine and 10 pyrimidine/water complexes with increasing water
      content. Also, accurate structure-spectra correlations for different cluster
      subgroups have been determined; within each particular cluster subgroup the water
      content varies, and a perfect negative correlation between NH hydrogen-bond
      distances and nu1 wavenumbers was observed.

PMID- 17523604
TI  - Matrix infrared spectroscopic studies of the MH-C2H3 and MH2-C2H2 intermediates
      in the reactions of ethylene with laser-ablated group 5 metal atoms.
AB  - Reactions of ethylene with laser-ablated group 5 metal atoms in excess argon have
      been carried out during codeposition at 8 K, and the matrix infrared spectra of
      intermediate products have been investigated. Oxidative C-H insertion of the
      transition metal into a C-H bond occurs and beta-hydrogen transfer follows to
      form the dihydrido complexes (MH2-C2H2). In the Ta spectra, the dihydrido complex
      is the primary product, whereas the Nb and V spectra reveal absorptions from both
      the insertion (MH-C2H3) and dihydrido complexes. The insertion and dihydrido
      complexes identified here are in fact the reaction intermediates in the hydrogen
      elimination of ethylene proposed in previous reaction dynamics studies.
      Calculations also show that the higher oxidation-state complex becomes more
      stable relative to the insertion product going down the group 5 family.

PMID- 17523605
TI  - Theoretical study of the reaction mechanisms involved in the thermal
      intramolecular reactions of 1,6-fullerenynes.
AB  - Substitution of a H atom by an alkyl group on the terminal carbon of the alkyne
      moiety of 1,6-fullerenynes has a strong impact on the products of the reaction
      undergone by this species after thermal treatment. While the reaction of 1,6
      fullerenynes bearing an unsubstituted alkyne moiety results in the cycloaddition
      of the alkyne group to the fullerene double bond leading to cyclobutene-fused
      derivatives, the presence of an alkyl substituent leads to the formation of
      allenes. In the present work, we have performed an exhaustive theoretical
      analysis of all possible reaction mechanisms leading to cyclobutene-fused
      derivatives and allenes to offer an explanation of the reactivity differences
      observed. The results obtained show that formation of cyclobutene-fused
      derivatives occurs through a stepwise diradical reaction mechanism, while allene
      formation proceeds through a concerted way involving an uncommon intramolecular
      ene process. For the 1,6-fullerenynes bearing a substituted alkyne, the ene
      reaction path leading to allenes has an energy barrier somewhat lower than the
      stepwise diradical mechanism for the cyclobutene-fused derivative formation, thus
      explaining the outcome of the reaction.

PMID- 17523606
TI  - Structures and cis-to-trans photoisomerization of hexafluoro-1,3-butadiene
      radical cation: electron spin resonance and computational studies.
AB  - The s-cis and s-trans isomer radical cations of hexafluoro-1,3-butadiene (s-cis
      HFBD+ and s-trans-HFBD+) were generated by a gamma-irradiated solid solution of
      the neutral HFBD molecule in solid matrix at 77 K and observed by means of
      electron spin resonance (ESR) and electronic spectroscopies. In comparing the
      experimental isotropic and anisotropic 19F hyperfine splittings with the
      computational ones by the DFT B3LYP and MP2 methods, the generated s-cis-HFBD+
      and s-trans-HFBD+ radical cations were confirmed to be 2A2 and 2Bg electronic
      ground states in C2v and C2h symmetries, respectively. The present spectroscopic
      study revealed that the relative abundance of s-cis-HFBD+ to s-trans-HFBD+ was
      4.0 immediately after being formed by gamma-irradiation, and subsequently most s
      cis-HFBD+ was isomerized to s-trans-HFBD+ by visible-light illumination with 500
      600 nm wavelength. The process of nonplanar HFBD ionizing to form stable planar s
      cis- and s-trans-HFBD+ and the reaction mechanism of the cis-to-trans
      photoisomerization were discussed by (MS-)CASPT2//CASSCF calculated vertical
      excitation energies (Tv) and torsional potential energy curves (TPECs) of HFBD
      and HFBD+.

PMID- 17523607
TI  - Watching Na atoms solvate into (Na+,e-) contact pairs: untangling the ultrafast
      charge-transfer-to-solvent dynamics of Na- in tetrahydrofuran (THF).
AB  - With the large dye molecules employed in typical studies of solvation dynamics,
      it is often difficult to separate the intramolecular relaxation of the dye from
      the relaxation associated with dynamic solvation. One way to avoid this
      difficulty is to study solvation dynamics using an atom as the solvation probe;
      because atoms have only electronic degrees of freedom, all of the observed
      spectroscopic dynamics must result from motions of the solvent. In this paper, we
      use ultrafast transient absorption spectroscopy to investigate the solvation
      dynamics of newly created sodium atoms that are formed following the charge
      transfer to solvent (CTTS) ejection of an electron from sodium anions (sodide) in
      liquid tetrahydrofuran (THF). Because the absorption spectra of the sodide
      reactant, the sodium atom, and the solvated electron products overlap, we first
      examined the dynamics of the ejected CTTS electron in the infrared to build a
      detailed model of the CTTS process that allowed us to subtract the spectroscopic
      contributions of the sodide bleach and the solvated electron and cleanly reveal
      the spectroscopy of the solvated atom. We find that the neutral sodium species
      created following CTTS excitation of sodide initially absorbs near 590 nm, the
      position of the gas-phase sodium D-line, suggesting that it only weakly interacts
      with the surrounding solvent. We then see a fast solvation process that causes a
      red-shift of the sodium atom's spectrum in approximately 230 fs, a time scale
      that matches well with the results of MD simulations of solvation dynamics in
      liquid THF. After the fast solvation is complete, the neutral sodium atoms
      undergo a chemical reaction that takes place in approximately 740 fs, as
      indicated by the observation of an isosbestic point and the creation of a species
      with a new spectrum. The spectrum of the species created after the reaction then
      red-shifts on a approximately 10-ps time scale to become the equilibrium spectrum
      of the THF-solvated sodium atom, which is known from radiation chemistry
      experiments to absorb near approximately 900 nm. There has been considerable
      debate as to whether this 900-nm absorbing species is better thought of as a
      solvated atom or a sodium cation:solvated electron contact pair, (Na+,e-). The
      fact that we observe the initially created neutral Na atom undergoing a chemical
      reaction to ultimately become the 900-nm absorbing species suggests that it is
      better assigned as (Na+,e-). The approximately 10-ps solvation time we observe
      for this species is an order of magnitude slower than any other solvation process
      previously observed in liquid THF, suggesting that this species interacts
      differently with the solvent than the large molecules that are typically used as
      solvation probes. Together, all of the results allow us to build the most
      detailed picture to date of the CTTS process of Na- in THF as well as to directly
      observe the solvation dynamics associated with single sodium atoms in solution.

PMID- 17523608
TI  - Kinetics for the reactions of O- and O2- with O2(a1Deltag) measured in a selected
      ion flow tube at 300 K.
AB  - The kinetics of the reactions of O- and O2- with O2(a1Deltag) have been studied
      at 300 K in a selected ion flow tube (SIFT). The O2(a1Deltag) concentrations have
      been determined using emission at 1270 nm from the O2(a1Deltag, v=0-->X3Sigmag-,
      v=0) transition measured with an InGaAs detector calibrated against absolute
      spectrally dispersed emission measurements. The rate constants measured for O-
      and O2- are 1.1x10(-10) and 6.6x10(-10) cm3 s-1, respectively, with uncertainties
      of +/-35%. The O2- reaction only produces electrons and can be described as
      Penning detachment, while the O- reaction has been found to produce both O2- and
      e-. The O2- branching fraction has a lower limit of approximately 0.30.
      Comparison of the present results to previous measurements found in the
      literature provides a resolution to a previous discrepancy in the rate constant
      values.

PMID- 17523609
TI  - Spin-orbit relativistic time-dependent density functional calculations of the
      metal and ligand pre-edge XAS intensities of organotitanium complexes: TiCl4,
      Ti(eta5-C5H5)Cl3, and Ti(eta5-C5H5)2Cl2.
AB  - Time-dependent density functional theory (TDDFT) coupled to the relativistic two
      component zeroth-order regular approximation, both available in the last version
      of the ADF package, have been successfully used to simulate X-ray absorption
      spectra of TiCl4, Ti(eta5-C5H5)Cl3, and Ti(eta5-C5H5)2Cl2 in terms of their
      oscillator strength distributions. Besides allowing a first principle assignment
      of Ti 1s, Cl 1s, and Ti 2p (L2,3 edges) core excitation spectra, theoretical
      outcomes provide a rationale for deviations from the expected L3/L2 branching
      ratio.

PMID- 17523610
TI  - Syntheses of potent, selective, and orally bioavailable indazole-pyridine series
      of protein kinase B/Akt inhibitors with reduced hypotension.
AB  - Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally
      bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While
      promising efficacy was observed in vivo, this compound showed effects on
      depolarization of Purkinje fibers in an in vitro assay and CV hypotension in
      vivo. Guided by an X-ray structure of 7 bound to protein kinase A, which has 80%
      homology with Akt in the kinase domain, our efforts have focused on structure
      activity relationship (SAR) studies of the phenyl moiety, in an attempt to
      address the cardiovascular liability and further improve the Akt potency. A novel
      and efficient synthetic route toward diversely substituted phenyl derivatives of
      7 was developed utilizing a copper-mediated aziridine ring-opening reaction as
      the key step. To improve the selectivity of these Akt inhibitors over other
      protein kinases, a nitrogen atom was incorporated into selected phenyl analogues
      of 7 at the C-6 position of the methyl indazole scaffold. These modifications
      resulted in the discovery of inhibitor 37c with greater potency (IC50 = 0.6 nM vs
      Akt), selectivity, and improved cardiovascular safety profile. The SARs,
      pharmacokinetic profile, and CV safety of selected Akt inhibitors will be
      discussed.

PMID- 17523611
TI  - Quantitation of multisite EGF receptor phosphorylation using mass spectrometry
      and a novel normalization approach.
AB  - Using stable isotope labeling and mass spectrometry, we performed a sensitive,
      quantitative analysis of multiple phosphorylation sites of the epidermal growth
      factor (EGF) receptor. Phosphopeptide detection efficiency was significantly
      improved by using the tyrosine phosphatase inhibitor sodium pervanadate to boost
      the abundance of phosphorylation of the EGF receptor. Nine phosphorylation sites
      (pT669, pS967, pS1002, pY845, pY974, pY1045, pY1086, pY1148, and pY1173) of EGF
      receptor were quantified from EGF-stimulated cells in suspension and adherent
      conditions. Our data sets revealed that EGF stimulation of adherent cells induced
      higher levels of tyrosine phosphorylation relative to EGF stimulation of
      suspended cells. In contrast, EGF stimulation of adherent cells induced lower
      levels of serine and threonine phosphorylation relative to EGF stimulation of
      suspended cells. These findings are consistent with the hypothesis that cellular
      adhesion modulates phosphorylation of plasma membrane receptor tyrosine kinases
      relevant for EGF-induced signal transduction processes. Furthermore, our results
      suggest that strong phosphatase inhibitors should be used to generate reference
      datasets in comparative phosphoproteomics experiments.

PMID- 17523612
TI  - Profiling the Bordetella pertussis proteome during iron starvation.
AB  - Regulation of gene expression in response to local iron concentration is commonly
      observed in bacterial pathogens that face this nutrient limitation during host
      infection. In this study, a proteomic approach was used to analyze the
      differential protein expression of Bordetella pertussis under iron limitation.
      Whole cell lysates (WCL) and outer membrane fractions of bacteria grown either
      under iron-starvation or iron-excess conditions were analyzed by two-dimensional
      (2-D) gel electrophoresis. Statistical analysis revealed 36 proteins displaying
      differential expression, 9 with higher expression under iron-excess and 27 with
      increased expression under iron-starvation. These proteins were subjected to
      tryptic digestion and MALDI-TOF MS. Apart from those previously reported, we
      identified new low-iron-induced proteins that might help to explain the increased
      virulence of this phenotype. Additionally, we found evidence that at least one of
      the identified proteins, solely expressed under iron starvation, is highly
      immunogenic in infected individuals.

PMID- 17523613
TI  - Direct on-membrane glycoproteomic approach using MALDI-TOF mass spectrometry
      coupled with microdispensing of multiple enzymes.
AB  - We report a novel approach for direct on-membrane glycoproteomics by digestion of
      membrane-blotted glycoproteins with multiple enzymes using piezoelectric chemical
      inkjet printing technology and on-membrane direct MALDI-TOF mass spectrometry.
      With this approach, both N-linked glycan analyses and peptide mass fingerprinting
      of several standard glycoproteins were successfully performed using PNGase F and
      trypsin microscale digestions of the blotted spots on membrane from an SDS-PAGE
      gel. In addition, we performed a similar analysis for 2-DE separated serum
      glycoproteins as a demonstration of how the system could be used in human plasma
      glycoproteomics.

PMID- 17523614
TI  - Identification of candidate biomarker proteins released by human endometrial and
      cervical cancer cells using two-dimensional liquid chromatography/tandem mass
      spectrometry.
AB  - Candidate biomarker proteins, including chaperonin 10 and pyruvate kinase,
      previously discovered and identified using mass-tagging reagents with
      multidimensional liquid chromatography and tandem mass spectrometry (DeSouza, L.;
      et al. J. Proteome Res. 2005, 4, 377-386) have been identified in serum-free
      media of cultured endometrial cancer (KLE and HEC-1-A) and cervical cancer (HeLa)
      cells. These and other cancer-associated proteins were released by the cultured
      cells within 24 h of growth. A total of 203 proteins from the KLE cells, 86 from
      HEC-1-A, and 161 from HeLa are reported.

PMID- 17523616
TI  - Virtual screening studies to design potent CDK2-cyclin A inhibitors.
AB  - The cell division cycle is controlled by cyclin-dependent kinases (CDK), which
      consist of a catalytic subunit (CDK1-CDK8) and a regulatory subunit (cyclin A-H).
      Pharmacophore analysis indicates that the best inhibitor model consists of (1)
      two hydrogen bond acceptors, (2) one hydrogen bond donor, and (3) one hydrophobic
      feature. The HypoRefine pharmacophore model gave an enrichment factor of 1.31 and
      goodness of fit score of 0.76. Docking studies were carried out to explore the
      structural requirements for the CDK2-cyclin A inhibitors and to construct highly
      predictive models for the design of new inhibitors. Docking studies demonstrate
      the important role of hydrogen bond and hydrophobic interactions in determining
      the inhibitor-receptor binding affinity. The validated pharmacophore model is
      further used for retrieving the most active hits/lead from a virtual library of
      molecules. Subsequently, docking studies were performed on the hits, and novel
      series of potent leads were suggested based on the interaction energy between
      CDK2-cyclin A and the putative inhibitors.

PMID- 17523617
TI  - Electron transfer between guanosine radical and amino acids in aqueous solution.
      1. Reduction of guanosine radical by tyrosine.
AB  - As a model of chemical DNA repair, the reductive electron transfer from the
      aromatic amino acid tyrosine to the radical of the purine base guanosine
      monophosphate (GMP) was studied by time-resolved chemically induced dynamic
      nuclear polarization (CIDNP). The guanosyl radicals were photochemically
      generated in the quenching reaction of the triplet excited dye 2,2'-dipyridyl.
      Depending on the pH of the aqueous solution, four different guanosyl radicals
      were observed. The identification of the radicals was possible because of the
      high sensitivity of CIDNP to distinguish them through their ability or disability
      of participating in the degenerate electron hopping reaction with the diamagnetic
      molecules of guanosine monophosphate in the ground state. The CIDNP kinetics in
      this three-component system containing the dye, GMP, and N-acetyl tyrosine is
      strongly dependent on the efficiency of the electron-transfer reaction from
      tyrosine to the nucleotide radical. Quantitative analysis of the CIDNP kinetics
      obtained at different concentrations of the amino acid, together with the
      comparison with the CIDNP kinetics of the two-component systems
      (dipyridyl/tyrosine and dipyridyl/GMP) allowed for the determination of the rate
      constant ke of the reductive electron-transfer reaction for five pairs of
      reactants, with different protonation states depending on the pH: GH++*/TyrOH (pH
      1.3), G+*/TyrOH (pH 2.9), G(-H)*/TyrOH (pH 7.5), G(-H)*/TyrO- (pH 11.3), and G(
      2H)-*/TyrO- (pH 13.3). The rate constant ke varies from (7.1 +/- 3.0) x 10(8) M-1
      s-1 (pH 1.3, 2.9) to less than 6 x 10(6) M-1 s-1 (pH 13.3).

PMID- 17523618
TI  - High-pressure induced conformational and phase transformations of 1,2
      dichloroethane probed by Raman spectroscopy.
AB  - 1,2-Dichloroethane (DCE) was loaded into diamond anvil cells and compressed up to
      30 GPa at room temperature. Pressure-induced transformations were probed using
      Raman spectroscopy. At pressures below 0.6 GPa, fluid DCE exists in two
      conformations, gauche and trans in equilibrium, which is shifted to gauche on
      compression. DCE transforms to a solid phase with exclusive trans conformation
      upon further compression. All the characteristic Raman shifts remain constant in
      fluid phase and move to higher frequencies in the solid phase with increasing
      pressure. At about 4-5 GPa, DCE transforms from a possible disordered phase into
      a crystalline phase as evidenced by the observation of several lattice modes and
      peak narrowing. At 8-9 GPa, dramatic changes in Raman patterns of DCE were
      observed. The splitting of the C-C-Cl bending mode at 325 cm-1, together with the
      observation of inactive internal mode at 684 cm-1 as well as new lattice modes
      indicates another pressure-induced phase transformation. All Raman modes exhibit
      significant changes in pressure dependence at the transformation pressure. The
      new phase remains crystalline, but likely with a lower symmetry. The observed
      transformations are reversible in the entire pressure region upon decompression.

PMID- 17523619
TI  - Characterization of the galectin-1 carbohydrate recognition domain in terms of
      solvent occupancy.
AB  - Human galectin-1, a galactosil-terminal sugar binding soluble protein, is a
      potent multifunctional effector that participates in specific protein
      carbohydrate and protein-protein interactions. Recent studies revealed that it
      plays a key role as a modulator of cellular differentiation and immunological
      response. In this work, we have investigated the solvation properties of the
      carbohydrate recognition domain of Gal-1 by means of molecular dynamics
      simulations. Water sites (ws) were identified in terms of radial and angular
      distribution functions, and properties such as water residence times, interaction
      energies, and free-energy contributions were evaluated for those sites. Our
      results allowed us to correlate the thermodynamic properties of the ws and their
      binding pattern with the N-acetilgalactoside ligand. These results let us further
      infer that the water molecules located at the ws, which exhibit much more
      favorable binding, are the ones replaced by -OH groups of the sugar.

PMID- 17523620
TI  - Polyelectrolyte-modified inverse microemulsions and their use as templates for
      the formation of magnetite nanoparticles.
AB  - This paper is focused on the characterization of polyelectrolyte-modified inverse
      microemulsions and their use as templates for the synthesis of magnetite
      nanoparticles. It is shown that the cationic polyelectrolyte
      poly(diallyldimethylammonium chloride) (PDADMAC) of low molar mass can be
      incorporated into the individual inverse microemulsion droplets (L2 phase)
      consisting of heptanol, water, and an amphoteric surfactant with a sulfobetaine
      head group. Up to a polymer concentration of 20% by weight in the aqueous phase
      and for different molecular weights of the polymer, an isotropic phase still
      exists. At a PDADMAC concentration of 10% the area of the isotropic L2 phase is
      shifted in direction to the water corner. In the percolated area of the L2 phase,
      i.e., at higher water content, a temperature-dependent change in the conductivity
      can by observed, and bulk water can be detected by means of differential scanning
      calorimetry measurements. The unusual temperature-dependent behavior of the
      polymer-modified system, i.e., the conductivity decrease with increasing
      temperature, can be explained by temperature-sensitive polyelectrolyte-surfactant
      interactions, influencing the droplet-droplet interactions. These PDADMAC
      modified microemulsions can be successfully used as a template for the formation
      of ultrafine magnetite particles, in contrast to the nonmodified microemulsion,
      where the process is misdirected due to the "disturbing" effect of the
      surfactants. However, in the presence of PDADMAC the surfactant head groups were
      masked, and therefore magnetite can be synthesized. During the process of
      magnetite formation the PDADMAC controls the particle growing and stabilizes
      spherical magnetite particles with a diameter of 17 nm, which can be redispersed
      without a change in size.

PMID- 17523621
TI  - Triplet excited fluoroquinolones as mediators for thymine cyclobutane dimer
      formation in DNA.
AB  - A series of fluoroquinolones (FQs), including enoxacin (ENX), pefloxacin (PFX),
      norfloxacin (NFX), its N(4')-acetyl derivative (ANFX), ofloxacin (OFX), and
      rufloxacin (RFX) have been investigated to determine their potential as DNA
      photosensitizers via thymine cyclobutane dimer (T<>T) formation in DNA. At
      fluoroquinolone concentrations and light doses insufficient to produce direct
      single strand breaks, ENX, PFX, and NFX were able to produce T<>T dimers in DNA,
      revealed by enzymatic treatment with T4 endonuclease V. By contrast, ANFX, OFX,
      and RFX were inefficient in this assay. The absolute values of the triplet
      energies of ENX, PFX, NFX, ANFX, OFX, and RFX were estimated by means of laser
      flash photolysis, using flurbiprofen, 4-biphenylcarboxylic acid, and naproxen as
      energy acceptors. They were found to be 273, 269, 269, 265, 262, and 253 kJ/mol,
      respectively. Other triplet excited state properties of the FQs, including
      quantum yields and lifetimes, were also studied. All the results indicate that
      the threshold ET value required for a given compound to become a potential DNA
      photosensitizer via T<>T formation is in the range defined by the triplet
      energies of NFX and ANFX (265-269 kJ/mol). This provides the basis for an alert
      rule: any chemical (drugs, cosmetics, pesticides, etc.) with higher ET has to be
      considered with regard to its potential photogenotoxicity.

PMID- 17523622
TI  - Electrolyte-induced mesoscopic aggregation of thiacarbocyanine dye in aqueous
      solution: counterion size specificity.
AB  - Countercation size specificity is presented for the electrolyte-induced
      aggregation of 3,3'-disulfopropyl-5,5'-dichloro-9-methyl thiacarbocyanine (TCC)
      dye in aqueous solution. Addition of electrolytes having a small monovalent
      cation (Na+, NH4+, or Cs+) induced pure H aggregates of TCC, whereas J aggregates
      were preferentially promoted by electrolytes with a large monovalent cation
      ([N(CH3)4]+ or [N(C2H5)4]+). The electrolyte-induced H aggregate (HS aggregate)
      differed spectroscopically from that spontaneously self-assembled in aqueous
      solution. Mesoscopic structure of the HS aggregates was revealed via polarized
      light microscopy and atomic force microscopy; a rodlike morphology of 50-70 nm
      wide and tens to hundreds of micrometers long with very strong negative
      birefringence. A simple structural model based on semiempirical molecular orbital
      calculations can explain the aggregation behaviors: The anionic TCC monomer shows
      a considerable planar geometry between two benzothiazole end groups when it
      involves a sodium cation, which favors the H-type molecular arrangements in a
      face-to-face orientation. On the other hand, the TCC dye has a twisted
      conformation when it implicates a large tetramethylammonium cation, resulting in
      the formation of the J aggregates.

PMID- 17523623
TI  - Rate and driving force for protonation of aryl radical anions in ethanol.
AB  - Aryl radical anions created in liquid alcohols decay on the microsecond time
      scale by transfer of protons from the solvent. This paper reports a 4.5 decade
      range of rate constants for proton transfer from a single weak acid, ethanol, to
      a series of unsubstituted aryl radical anions, Ar-*. The rate constants correlate
      with free energy change, DeltaG(o), despite wide variations in the two factors
      that contribute to DeltaG(o): (a) the reduction potentials of the aryls and (b)
      the Ar-H* bond strengths in the product radicals. For aryl radical anions
      containing CH2OH substituents, such as 2,2'-biphenyldimethanol*- which is
      protonated with a rate constant of 3x10(9) s(-1), the faster rates do not fit
      well in the free energy correlation, suggesting a change in mechanism.

PMID- 17523624
TI  - Photophysical and density functional studies of the interaction of a flavone
      derivative with the halides.
AB  - The synthesis, photophysical behavior, and anion-sensing ability of a fluorescent
      molecular system, N-(3-methoxy-4-oxo-2-phenyl-4H-chromen-7-yl)-benzamide (1H),
      designed and developed with a view to sensing fluoride ions, are reported. NMR
      and density functional studies on the system have been carried out to determine
      the nature of the interaction between 1H and X- (X = halogen atom) responsible
      for fluoride-induced dramatic changes in the absorption and emission properties
      of 1H. The color change of 1H, which can be observed by the naked eye, is found
      specific to fluoride ion; it is unaffected by the presence of a large excess of
      Cl-, Br-, and I-, thus rendering 1H as a selective fluoride ion sensor in
      micromolar concentration in the visible region. The changes in the fluorescence
      behavior of 1H, specifically, the formation of an additional long-wavelength
      emission band in the presence of fluoride ion, allow ratiometric fluorescence
      signaling of the fluoride ion as well. The results suggest that abstraction of
      the acidic proton of 1H by the F- leading to the formation of 1- is responsible
      for the spectral changes that allow signaling of the F-. Density functional
      calculations of the optimized geometrical parameters and charge densities of the
      1H...halide complexes confirm the proton abstraction mechanism of the signaling
      of F-. Calculations of the transition energies of the 1H, 1-, and 1H...F-
      (hydrogen-bonded complex) show that only 1- is responsible for the long
      wavelength absorption and emission band observed in the presence of F-.

PMID- 17523625
TI  - One more type of extrathermodynamic relationship.
AB  - A new type of extrathermodynamic relationship is presented: DeltaH = Ti[DeltaS +
      R Delta(ln Omega)] + beta, where Omega is the phase volume and beta is a
      constant. This type of relationship holds for a series of systems in the case
      where deltaDelta(ln Omega) is changeable. The relation between this type of
      correlation and linear free-energy relationships is shown. An example of the
      specified correlation for energy parameters of excimers forming in different
      dipyrenylalkanes is demonstrated.

PMID- 17523626
TI  - Triplet energy studies of thiophene and para-phenylene based oligomers.
AB  - A series of conjugated materials based on oligomers of the para-phenylene type
      and oligothiophenes was prepared, and their phosphorescence spectra were recorded
      at 77 K using a pulsed flash-lamp as a light source and gated detection. The
      triplet energies of the oligomers were estimated and correlated with their
      chemical structure. It was found that simple changes in the building block
      sequence in the thiophene-containing oligomers allowed for tuning the triplet
      energy from 1.86 to 2.35 eV (530-670 nm). Hypsochromic shifts and little
      variation of the triplet energy were obtained with increasing length of the pi
      system for thiophene end-capped oligomers, contrary to the usual behavior of
      unsubstituted oligomers. The experimental results were supported with theoretical
      computations from density functional theory (B3LYP/6-31G*) calculations, which
      indicated that changes in the geometry and delocalization of the triplet excited
      state account for the trends in the triplet energy evolution.

PMID- 17523627
TI  - Picosecond protein response to the chromophore isomerization of photoactive
      yellow protein: selective observation of tyrosine and tryptophan residues by time
      resolved ultraviolet resonance Raman spectroscopy.
AB  - Picosecond time-resolved ultraviolet resonance Raman (UVRR) spectra of
      photoactive yellow protein (PYP) were measured. UVRR bands attributed to the
      vibration of tyrosine and tryptophan residues showed a spectral change upon
      photoreaction. It was found that the hydrogen-bond strength between the
      chromophore and Y42 increases in the pG* state. The ultrafast change in the
      tryptophan band revealed that a photoinduced structural change of the chromophore
      had propagated to the W119 region, located 12 A from the chromophore, within
      picoseconds.

PMID- 17523628
TI  - Coordination mode of nitrate in uranyl(VI) complexes: a first-principles
      molecular dynamics study.
AB  - According to Car-Parrinello molecular dynamics simulations for [UO(2)(NO(3))(3)](
      ), [UO(2)(NO(3))(4)](2-), and [UO(2)(OH(2))(4-)(NO(3))](+) complexes in the gas
      phase and in aqueous solution, the nitrate coordination mode to uranyl depends on
      the interplay between ligand-metal attractions, interligand repulsions, and
      solvation. In the trinitrate, the eta(2)-coordination is clearly favored in water
      and in the gas phase, leading to a coordination number (CN) of 6. According to
      pointwise thermodynamic integration involving constrained molecular dynamics
      simulations, a change in free energy of +6 kcal/mol is predicted for eta(2)- to
      eta(1)-transition of one of the three nitrate ligands in the gas phase. In the
      gas phase, the mononitrate-hydrate complex also prefers a eta(2)-binding mode but
      with a CN of 5, one H(2)O molecule being in the second shell. This contrasts with
      the aqueous solution where the nitrate binds in a eta(1)-fashion and uranyl
      coordinates to four H2O ligands. A driving force of ca. -3 kcal/mol is predicted
      for the eta(2)- to eta(1)- transition in water. This structural preference is
      interpreted in terms of steric arguments and differential solvation of terminal
      vs uranyl-coordinated O atoms of the nitrate ligands. The [UO(2)(NO(3))(4)](2-)
      complex with two eta(2)- and two eta(1)- coordinated nitrates, observed in the
      solid state, is stable for 1-2 ps in the gas phase and in solution. In the
      studied series, the modulation of uranyl-ligand distances upon immersion of the
      complex in water is found to depend on the nature of the ligand and the
      composition of the complex.

PMID- 17523629
TI  - Complexes of aminosquarate ligands with first-row transition metals and
      lanthanides: new insights into their hydrolysis.
AB  - Attempts at synthesizing first-row transition-metal complexes of the 3-hydroxy-4
      [(1'S,2'R)-(2-hydroxy-1',2'-diphenylethyl)amino]-3-cyclobutene-1,2-dione ligand
      in alcoholic solutions resulted in the formation of the monomers
      [M(NH(2)C(4)O(3))(2)(H(2)O)(4)] [M = Mn (1), Co (2), Ni (3), Cu (4), Zn (5)]
      instead, as a result of the hydrolysis of the ligand. 1, 2, and 3 are isomorphous
      (C2/c), with the metal atoms octahedrally coordinated to four aqua and two cis
      aminosquarate ligands. The copper and zinc complexes (4 and 5) have the same
      molecular formula as 1-3 but belong to the C2/m and P2(1)/c space groups
      respectively. 4 has square-pyramidal geometry with trans-oriented aminosquarate
      ligands in the basal plane; aqua ligands complete the coordination sphere. 5 has
      octahedral geometry, with four aqua and two trans-oriented aminosquarate ligands.
      Reaction of aqueous solutions of the anilinosquarate ligand with Ln(NO(3))(3) x
      xH(2)O produced the eight-coordinate complexes {Sm(mu
      C(6)H(5)NHC(4)O(3))(3)(H(2)O)(4) x 3H(2)O}n (6), {[M(mu(2)
      C(4)O(4))(H(2)O)(6)][C(6)H(5)NHC(4)O(3)] x 4H(2)O}n [M = Er (7), Yb (8)],
      {Sm(C(6)H(5)NHC(4)O(3)) (mu(3)-C(4)O(4))(H(2)O)(4) x H(2)O}(n) (9), and
      {[{(C(6)H(5)NHC(4)O(3))(2)(H(2)O)(5)Yb}(2)(mu-C(4)O(4))] x 4H(2)O}n (10). 7 and 8
      are isomorphous with the previously reported analogues Eu, Gd, and Tb ionic
      polymers. The presence of the squarate ligand in 7-10 is indicative of some form
      of hydrolysis of the anilinosquarate ligand during their syntheses. However,
      hydrolysis was not evident in the synthesis of 6. The mechanism for the
      hydrolysis in the syntheses of 1-5 is apparently different from that for 7-10.

PMID- 17523630
TI  - Selective reaction based on the linked diamido ligands of dinuclear lanthanide
      complexes.
AB  - The dinuclear ytterbium pyridyl diamido complexes [Cp(2)Yb(THF)](2)[mu
      eta(1):eta(2)-(NH)(2)(C(5)H(3)N-2,6)] (1a) and [Cp(2)Yb(THF)](2)[mu-eta(1):eta(2)
      (NH)(2)(C(5)H(3)N-2,3)] (1b) are easily prepared by protonolysis of Cp(3)Yb with
      0.5 equiv of the corresponding diaminopyridine in accepted yields, respectively.
      Treatment of 1a with 2 equiv of dicyclohexylcarbodiimide (CyN=C=NCy) in THF at
      low temperature leads to the isolation of the formal double N-H addition product
      (Cp(2)Yb)(2)[mu-eta(2):eta(2)-(CyN(CyNH)CN)(2)(C(5)H(3)N-2,6)] (2) in 42% yield.
      Compound 2 is unstable to heat and slowly isomerized to the mixed
      neutral/dianionic diguanidinate complex (Cp(2)Yb)(2)[mu-eta(2):eta(2)
      (CyNH)(2)CN(C(5)H(3)N-2,6)NC(NCy)(2)](THF) (3) at room temperature. Similarly,
      treatment of 1b with 2 equiv of CyN=C=NCy gives the addition/ isomerization
      product (Cp(2)Yb)(2)[mu-eta(2):eta(2):eta(1)-(CyNH)(2)CN(C(5)H(3)N
      2,3)NC(NCy)(2)] (4). Moreover, the reaction of various ytterbium aryl diamido
      complexes (prepared in situ from [Cp(2)YbMe](2) and aryldiamine, respectively)
      with CyN=C=NCy affords the corresponding addition products (Cp(2)Yb)(2)[mu
      eta(2):eta(2)-{CyN(CyNH)CN}(2)(C(6)H(4)-1,4)] (5), (Cp(2)Yb)(2)[mu-eta(2):eta(2)
      {CyN(CyNH)CN}(2)(C(6)H(4)-1,3)](6), and (Cp(2)Yb)(2)[mu-eta(2):eta(2)
      {CyN(CyNH)CN}(2)(C(13)H(8)-2,7)] (7), respectively. In contrast to pyridyl
      bridged bis(guanidinate monoanion) complexes, aryl-bridged bis(guanidinate
      monoanion) complexes 5-7 are stable even with prolonged heating at 110 degrees C.
      All the results not only demonstrate that the presence of the pyridyl bridge can
      impart the diamido complexes with a unique reactivity and initiate the unexpected
      reaction sequence but also indicate evidently that the number and distribution of
      negative charges of the diguanidinate ligand is tunable from double monoanionic
      units to mixed neutral/dianionic isomers. All the complexes are characterized by
      elemental analysis and IR spectroscopies. The structures of complexes 1a, 3, 5,
      6, and 7 are also determined through X-ray single-crystal diffraction analysis.

PMID- 17523631
TI  - Double-icosahedral Li clusters in a new binary compound Ba(19)Li(44): a
      reinvestigation of the Ba-Li phase diagram.
AB  - The binary Ba-Li system was reinvestigated for compositions with less than 80 at.
      % Li. A new compound, Ba(19)Li(44), stable up to 126 degrees C, was found and
      structurally characterized. According to single-crystal X-ray diffraction data,
      the compound crystallizes in a new structure type with a tetragonal unit cell,
      space group I42d, a = 16.3911(5) Angstrom, c = 32.712(1) Angstrom, Z = 4, and V =
      8788.7(5) Angstrom(3). It can be described as a complicated variant of the
      chalcopyrite structure. Typical for Li-rich phases, Ba(19)Li(44) contains
      icosahedron-based polytetrahedral clusters.

PMID- 17523632
TI  - Design and structure analysis of artificial metalloproteins: selective
      coordination of His64 to copper complexes with square-planar structure in the apo
      myoglobin scaffold.
AB  - apo-Myoglobin (apo-Mb) was reconstituted with three copper complexes: CuII(Sal
      Phe) (1; Sal-Phe = N-salicylidene-L-phenylalanato), CuII(Sal-Leu) (2; Sal-Leu = N
      salicylidene-L-leucinato), and CuII(Sal-Ala) (3; Sal-Ala = N-salicylidene-L
      alanato). The crystal structures of 1.apo-Mb (1.65 Angstrom resolution) and 2.apo
      Mb (1.8 Angstrom resolution) show that the coordination geometry around the CuII
      atom in apo-Mb is distorted square-planar with tridentate Sal-X and a Nepsilon
      atom of His64 in the apo-Mb cavity and the plane of these copper complexes is
      perpendicular to that of heme. These results suggest that the apo-Mb cavity can
      hold metal complexes with various coordination geometries.

PMID- 17523633
TI  - 3D coordination framework [Ln(4)(mu(3)-OH)(2)Cu(6)I(5)(IN)(8)(OAc)(3)] (IN =
      isonicotinate): employing 2D layers of lanthanide wheel clusters and 1D chains of
      copper halide clusters.
AB  - Two novel 3D heterometallic coordination polymers, Ln(4)(mu(3)
      OH)(2)Cu(6)I(5)(IN)(8)(OAc)(3) (Ln = Nd (1), Pr (2); HIN = isonicotinic acid,
      HOAc = acetic acid), have been synthesized under hydrothermal conditions and
      characterized by elemental, infrared, and thermogravimetric analyses and single
      crystal X-ray diffraction. Both compounds are isostructural and crystallize in
      the monoclinic system, space group P2(1)/c. Both polymers are constructed from 2D
      lanthanide-cluster polymers based on the {Ln(16)} wheel-cluster and 1D copper
      cluster polymers based on the {Cu(6)I(5)} cluster, which represent the first
      examples of 3D coordination frameworks created by using a combination of two
      different types of metal-cluster polymer units, namely, a high-nuclearity
      lanthanide-cluster polymer and a transition-metal-cluster polymer.

PMID- 17523634
TI  - Solution-chemical synthesis of carbon nanotube/ZnS nanoparticle core/shell
      heterostructures.
AB  - A facile solution-chemical method has been developed to be capable of
      encapsulating a multiwalled carbon nanotube (MWCNT) with ZnS nanocrystals without
      using any bridging species. The thickness of the ZnS shell can be tuned easily by
      controlling the experimental conditions. The optical properties of the MWCNT/ZnS
      heterostructures were investigated using UV-vis absorption and photoluminescence
      spectroscopy. The optical absorption spectrum indicates that the band gap of ZnS
      nanocrystallites is 4.2 eV. On the basis of the photoluminescence spectrum,
      charge transfer is thought to proceed from ZnS nanocrystals to the nanotube in
      the ZnS-carbon nanotube system. These special heterostructures are very easily
      encapsulated within a uniform silica layer by a modified-Stober process and still
      show better stability even after heat treatment at 400 degrees C, which makes
      them appealing for practical applications in biochemistry and biodiagnostics.

PMID- 17523635
TI  - Quasi-thermoneutral P --> B interactions within di- and tri-phosphine boranes.
AB  - Spectroscopic, structural, and theoretical evidence is provided for both open (no
      intramolecular P --> B interaction) and closed (with intramolecular P --> B
      interaction) forms of the di- and tri-phosphine boranes [o
      (iPr(2)P)C(6)H(4)](2)BPh (2) and [o-(iPr(2)P)C(6)H(4)](3)B (3).

PMID- 17523636
TI  - Which one among Zn(II), Co(II), Mn(II), and Fe(II) is the most efficient ion for
      the methionine aminopeptidase catalyzed reaction?
AB  - The catalytic hydrolysis of a methionyl-peptide substrate by a methionine
      aminopeptidase active site model cluster was investigated at the DF/B3LYP level
      of theory, in the gas-phase and in the protein environment. Zn(II), Co(II),
      Mn(II), and Fe(II) transition metals were examined as the potential catalytic
      metals of this enzyme involved in protein maturation. Two different mechanisms in
      which Glu204 was present as protonated or deprotonated residue were considered.
      The energetic profiles show lower barriers as the protonated glutamate is
      involved. The rate-determining step of the hydrolysis reaction is always the
      nucleophilic addition of the hydroxide on substrate carbon, followed by less
      energetically demanding methionine-peptide C-N bond scission. The lowest
      activation energy is obtained in the case of zinc dication while the other metals
      show very high energetic barriers, so that methionine aminopeptidase can be in
      principle recognized as a dizinc enzyme.

PMID- 17523637
TI  - Theory-guided design and synthesis of multichromophore dendrimers: an analysis of
      the electro-optic effect.
AB  - Extensive experimental and theoretical study suggests that interchromophore
      electrostatic interactions are among the most severe impediments to the induction
      and stability of large electro-optic coefficients in electric-field-poled organic
      materials. In this report, multichromophore-containing dendritic materials have
      been investigated as a means to minimize unwanted attenuation of nonlinear
      optical (electro-optic) activity at high chromophore loading. The dendritic
      molecular architectures employed were designed to provide optimized molecular
      scaffolding for electric-field-induced molecular reorientation. Design parameters
      were based upon past experimental results in conjunction with statistical and
      quantum mechanical modeling. The electro-optic behavior of these materials was
      evaluated through experimental and theoretical analysis. Experimental data
      collected from the dendrimer structures depict a reasonably linear relationship
      between chromophore number density (N) and electro-optic activity (r(33))
      demonstrating a deviation from the dipolar frustration that typically limits
      r(33) in conventional chromophore/polymer composite materials. The observed
      linear dependence holds at higher chromophore densities than those that have been
      found to be practical in systems of organic NLO chromophores dispersed in polymer
      hosts. Theoretical analysis of these results using Monte Carlo modeling
      reproduces the experimentally observed trends confirming linear dependence of
      electro-optic activity on N in the dendrimer materials. These results provide new
      insight into the ordering behavior of EO dendrimers and demonstrate that the
      frequently observed asymptotic dependence of electro-optic activity on
      chromophore number density may be overcome through rational design.

PMID- 17523638
TI  - Kinetic and spectroscopic studies of N694C lipoxygenase: a probe of the substrate
      activation mechanism of a nonheme ferric enzyme.
AB  - Lipoxygenases (LOs) comprise a class of substrate activating mononuclear nonheme
      iron enzymes which catalyze the hydroperoxidation of unsaturated fatty acids. A
      commonly proposed mechanism for LO catalysis involves H-atom abstraction by an
      FeIII-OH- site, best described as a proton coupled electron transfer (PCET)
      process, followed by direct reaction of O2 with the resulting substrate radical
      to yield product. An alternative mechanism that has also been discussed involves
      the abstraction of a proton from the substrate by the FeIII-OH leading to a sigma
      organoiron intermediate, where the subsequent sigma bond insertion of dioxygen
      into the C-Fe bond completes the reaction. H-atom abstraction is favored by a
      high E(o) of the FeII/FeIII couple and high pK(a) of water bound to the ferrous
      state, while an organoiron mechanism would be favored by a low E(o) (to keep the
      site oxidized) and a high pK(a) of water bound to the ferric state (to
      deprotonate the substrate). A first coordination sphere mutant of soybean LO
      (N694C) has been prepared and characterized by near-infrared circular dichroism
      (CD) and variable-temperature, variable-field (VTVH) magnetic circular dichroism
      (MCD) spectroscopies (FeII site), as well as UV/vis absorption, UV/vis CD, and
      electron paramagnetic resonance (EPR) spectroscopies (FeIII site). These studies
      suggest that N694C has a lowered E degrees of the FeII/FeIII couple and a raised
      pKa of water bound to the ferric site relative to wild type soybean lipoxygenase
      1 (WT sLO-1) which would favor the organoiron mechanism. However, the observation
      in N694C of a significant deuterium isotope effect, anaerobic reduction of iron
      by substrate, and a substantial decrease in k(cat) (approximately 3000-fold)
      support H-atom abstraction as the relevant substrate-activation mechanism in sLO
      1.

PMID- 17523639
TI  - Na(x)CoO(2): a new opportunity for rewritable media?

PMID- 17523640
TI  - A priori phase prediction of zeolites: case study of the structure-directing
      effects in the synthesis of MTT-type zeolites.
AB  - This study first uses molecular modeling to examine the structure-directing
      effects of small amines that are selective for the crystallization of MTT-type
      zeolite phases. The optimized van der Waals interactions of these small amines
      are compared within the one-dimensional pore zeolites with the MTT, TON, and MTW
      frameworks. From these results and our previous molecular modeling studies of
      structure-directing agents (SDA) for MTT-type zeolites, a large number of amines
      or quaternary ammonium molecules are successfully predicted to be selective for
      MTT phases. These molecules were chosen by matching the crystallographic
      periodicity of the pore structure with the distances between the centers of
      branched groups in these molecules. These molecules vary in length and in the
      number of branched moieties, and a few of these molecules are polymeric or
      oligomeric. In test cases where the distances between the branched groups are not
      multiples of the pore periodicity, with few exceptions these molecules usually do
      not produce MTT phases. Finally, we discuss the inorganic conditions necessary
      for crystallization of MTT phases in borosilicate preparations with some of the
      diamines in this investigation.

PMID- 17523641
TI  - Single-molecule conformational analysis of G-quadruplex formation in the promoter
      DNA duplex of the proto-oncogene c-kit.

PMID- 17523642
TI  - A nanotumbleweed: breaking away a covalently tethered polymer molecule by
      noncovalent interactions.
AB  - A covalently tethered polymer molecule can spontaneously break away from the
      surface when polymer/surface interaction is sufficiently unfavorable. This is
      demonstrated in surface-initiated polymerization of a hydrophilic polymer,
      hyperbranched polyglycidol, from minority surface sites embedded in a hydrophobic
      self-assembled monolayer. As each hyperbranched polyglycidol molecule grows
      larger, it encounters more unfavorable interaction with the hydrophobic surface,
      and this leads to spontaneous bond rupture and desorption. This finding
      challenges the traditional view on noncovalent interaction of macromolecules with
      the local environment at interfaces and has broad implications for the
      understanding, design, synthesis, and applications of surface-tethered
      macromolecules.

PMID- 17523643
TI  - Doubly ortho-linked cis-4,4'-bis(diarylamino)stilbene/fluorene hybrids as
      efficient nondoped, sky-blue fluorescent materials for optoelectronic
      applications.

PMID- 17523644
TI  - Sugar-assisted ligation in glycoprotein synthesis.
AB  - Sugar-assisted ligation (SAL) presents an attractive strategy for the synthesis
      of glycopeptides, including the synthesis of cysteine-free beta-O-linked and N
      linked glycopeptides. Here we extended the utility of SAL for the synthesis of
      alpha-O-linked glycopeptides and glycoproteins. In order to explore SAL in the
      context of glycoprotein synthesis, we developed a new chemical synthetic route
      for the alpha-O-linked glycoprotein diptericin epsilon. In the first stage of our
      synthesis, diptericin segment Cys(Acm)37-Gly(52) and segment Val(53)-Phe(82) were
      assembled by SAL through a Gly-Val ligation junction. Subsequently, after Acm
      deprotection, diptericin segment Cys(37)-Phe(82) was ligated to segment Asp(1)
      Asn(36) by means of native chemical ligation (NCL) to give the full sequence of
      diptericin epsilon. In the final synthetic step, hydrogenolysis was applied to
      remove the thiol handle from the sugar moiety with the concomitant conversion of
      mutated Cys(37) into the native alanine residue. In addition, we extended the
      applicability of SAL to the synthesis of glycopeptides containing cysteine
      residues by carrying out selective desulfurization of the sulfhydryl-modified
      sugar moiety in the presence of acetamidomethyl (Acm) protected cysteine
      residues. The results presented here demonstrated for the first time that SAL
      could be a general and useful tool in the chemical synthesis of glycoproteins.

PMID- 17523645
TI  - Dynamic interconversion of amorphous microparticles and crystalline rods in salen
      based homochiral infinite coordination polymers.

PMID- 17523646
TI  - Effect of doping on electronic transport through molecular monolayer junctions.

PMID- 17523647
TI  - Intramolecular C-H amination reactions: exploitation of the Rh(2)(II)-catalyzed
      decomposition of azidoacrylates.

PMID- 17523648
TI  - Iridium-catalyzed, asymmetric amination of allylic alcohols activated by Lewis
      acids.

PMID- 17523650
TI  - Fumimycin: a peptide deformylase inhibitor with an unusual skeleton produced by
      Aspergillus fumisynnematus.
AB  - Fumimycin, an unusual metabolite incorporating an unusual alanine unit linked to
      a phenyl group at the alpha-carbon with both lactone and amide moieties, was
      isolated from cultures of Aspergillus fumisynnematus. Its structure was
      established by spectral analysis. Fumimycin was found to inhibit Staphylococcus
      aureus peptide deformylase with an IC50 value of 4.1 microM and also showed
      antibacterial activity against S. aureus.

PMID- 17523651
TI  - Unexpected phenyl group rearrangement during an intramolecular Scholl reaction
      leading to an alkoxy-substituted hexa-peri-hexabenzocoronene.
AB  - A simple dimethoxy-substituted hexa-peri-hexabenzocoronene (m-dimethoxy HBC) was
      unexpectedly obtained along with a bis-spirocyclic dienone during an
      intramolecular Scholl reaction of its para isomer.

PMID- 17523652
TI  - Simple preparation of diamondoid 1,3-dienes via oxetane ring opening.
AB  - The transformations of apical mono- and bisacetyl diamondoids to the respective
      oxetanes and subsequent acid-catalyzed ring opening/dehydration lead to
      diamondoidyl mono- and bis-1,3-dienes in high preparative yields.

PMID- 17523653
TI  - The total synthesis of psymberin.
AB  - The total synthesis of a new member of the pederin family of natural products,
      psymberin 1, was accomplished. Using a recently reported novel and efficient
      PhI(OAc)2 mediated oxidative entry to 2-(N-acylaminal)-substituted
      tetrahydropyrans as the key step, this total synthesis was executed in a
      convergent and efficient manner. The longest linear sequence of this synthesis
      was 22 steps starting from known 6.

PMID- 17523654
TI  - Highly enantioselective Friedel-Crafts alkylations of indoles with simple enones
      catalyzed by zirconium(IV)-BINOL complexes.
AB  - Complexes of BINOL-based ligands with Zr(OtBu)4 catalyze the Friedel-Crafts
      alkylation reaction of indoles and pyrrole with nonchelating beta-substituted
      alpha,beta-enones at room temperature affording the expected products with good
      yields and ee above 95% in most of the studied examples.

PMID- 17523655
TI  - Novel hydrogels via click chemistry: synthesis and potential biomedical
      applications.
AB  - A novel procedure for the in situ rapid chemical gelation of aqueous solutions of
      hyaluronan has been employed. In brief, water-soluble polysaccharide derivatives
      bearing side chains endowed with either azide or alkyne terminal functionality
      have been prepared. When the latter two types of derivatives are mixed together
      in aqueous solution they give rise to a 1,3-dipolar cycloaddition reaction
      resulting in fast gelation (in the presence of catalytic amounts of Cu(I)) at
      room temperature. Gel formation has been characterized rheologically and could
      also be followed qualitatively by means of IR spectroscopy. The resulting gels
      have been studied in terms of swelling properties and, in particular, NMR
      spectral features. Carrying out the gelation process in aqueous solutions of
      benzidamine and doxorubicin, respectively, the polysaccharide networks acted as
      drug reservoirs. The doxorubicin release resulted in well controllable acting
      upon the gels degree of cross-linking. Finally, formation of the click-gels using
      aqueous suspensions of Saccharomices cerevisiae yeast cells allowed the
      obtainment of scaffolds inside which cells were homogeneously distributed and
      smoothly adhered to the inner pores surfaces, according to SEM analysis. After 24
      h about 60% of the entrapped cells exhibited proliferating activity. Click-gels
      prepared as detailed herein do have a number of positive features that make them,
      in perspective, materials of choice for drug release and tissue engineering
      manipulations.

PMID- 17523656
TI  - Cellulose fiber-enzyme composites fabricated through layer-by-layer nanoassembly.
AB  - Cellulose microfibers were coated with enzymes, laccase and urease, through layer
      by-layer assembly by alternate adsorption with oppositely charged polycations.
      The formation of organized polyelectrolyte and enzyme multilayer films of 15-20
      nm thickness was demonstrated by quartz crystal microbalance, zeta-potential
      analysis, and confocal laser scanning microscopy. These biocomposites retained
      enzymatic catalytic activity, which was proportional to the number of coated
      enzyme layers. For laccase-fiber composites, around 50% of its initial activity
      was retained after 2 weeks of storage at 4 degrees C. The synthesis of calcium
      carbonate microparticles on urease-fiber composites confirmed urease
      functionality and demonstrated its possible applications. This strategy could be
      employed to fabricate fiber-based composites with novel biological functions.

PMID- 17523657
TI  - Ethynyl ketene-S,S-acetals: the highly reactive electron-rich dienophiles and
      applications in the synthesis of 4-functionalized quinolines via a one-pot three
      component reaction.
AB  - An efficient synthetic method for 4-functionalized quinoline derivatives, 4-((1,3
      dithian-2-ylidene)methyl)quinolines, has been developed. Mediated by
      trifluoromethanesulfonic acid, ethynyl ketene-S,S-acetals can react in a one-pot
      procedure with various arylamines and aldehydes under mild conditions to give the
      corresponding quinoline derivatives in good to high yields via a consecutive
      arylimine formation, regiospecific aza-Diels-Alder (Povarov) reaction, and
      reductive amination.

PMID- 17523658
TI  - Toward the synthesis of norzoanthamine: complete fragment assembly.
AB  - The complex marine alkaloid norzoanthamine (2) was envisioned to be assembled
      from three key building blocks: the C1-C5 fragment A, the C6-C10 fragment B, and
      the C11-C24 fragment C. The synthesis of fragment A was achieved in 14 steps and
      33% overall yield from (R)-gamma-hydroxymethyl-gamma-butyrolactone. Fragment B
      was made in two steps from PMB-protected 4-pentynol in 76% yield. The C11-C24
      fragment C was made from (S)-carvone via (R)-isocarvone in 18 steps (6% overall
      yield). The convergent stereoselective synthesis of the entire carbon framework
      (C1-C24) of the target molecule was achieved via the following assemblage.
      Alkenyl iodide 20 derived from the C11-C24 fragment C was coupled to fragment B
      (C6-C10) through a high-yielding Stille coupling reaction of these two sterically
      very demanding coupling partners, affording the key Diels-Alder precursor 24. The
      intramolecular Diels-Alder reaction proceeded smoothly in excellent yield and
      diastereoselectivity, generating the tricyclic trans-anti-trans
      perhydrophenanthrene motif of norzoanthamine (C6-C24). The final fragment
      coupling between lithiated fragment A (C1-C5) and aldehyde 40 (C6-C24) has also
      been successfully accomplished affording the entire carbon framework of the
      natural product.

PMID- 17523659
TI  - One-pot synthesis of alpha-iodo-substituted alpha,beta-unsaturated aldehydes from
      propargylic alcohols.
AB  - An efficient one-pot method for the preparation of alpha-iodo-substituted
      alpha,beta-unsaturated aldehydes (alpha-iodoenals) from propargylic alcohol is
      developed. The reaction proceeds via an iodoallene intermediate, which is
      generated in situ by the reaction of propargylic alcohol with aqueous HI. The
      iodoallene intermediate is further transformed to an alpha-iodoenal derivative in
      good overall yield by oxidation with molecular O(2).

PMID- 17523660
TI  - Stereoselective total synthesis of bioactive styryllactones (+)-goniofufurone,
      (+)7-epi-goniofufurone, (+)-goniopypyrone, (+)-goniotriol, (+)-altholactone, and
      (-)-etharvensin.
AB  - Stereoselective total synthesis of biologically active styryllactones 7-epi
      goniofufurone, goniofufurone, goniopypyrone, goniotriol, altholactone, and
      etharvensin was achieved in high overall yields from a common intermediate
      derived from d-(-)-tartaric acid. It is based on the utility of a masked tetrol,
      comprising an alkene tether and four contiguous hydroxy groups. The pivotal
      reaction sequence involves hydroxy-directed lactonization via the oxidation of
      alkene, and subsequent elaboration to styryllactones. The masked tetrol was
      prepared by the extension of gamma-phenyl-gamma-hydroxy butyramide, readily
      obtained from the bis-dimethylamide of tartaric acid, employing a combination of
      selective Grignard additions and a stereoselective reduction.

PMID- 17523661
TI  - Colorimetric detection of Cu[II] cation and acetate, benzoate, and cyanide anions
      by cooperative receptor binding in new alpha,alpha'-bis-substituted donor
      acceptor ferrocene sensors.
AB  - New ferrocene derivatives bearing two donor-acceptor systems are capable of
      selectively sensing cations and anions by cooperative binding of the two
      alpha,alpha'-groups bonded to the ferrocene nucleus, thus permitting the naked
      eye selective colorimetric detection of copper[II] cation and acetate, benzoate,
      or cyanide anions, which are ions of toxicological and biological relevance.

PMID- 17523662
TI  - Synthesis and catalytic application of chiral 1,1'-Bi-2-naphthol- and
      biphenanthrol-based pincer complexes: selective allylation of sulfonimines with
      allyl stannane and allyl trifluoroborate.
AB  - New easily accessible 1,1'-bi-2-naphthol- (BINOL-) and biphenanthrol-based chiral
      pincer complex catalysts were prepared for selective (up to 85% enantiomeric
      excess) allylation of sulfonimines. The chiral pincer complexes were prepared by
      a flexible modular approach allowing an efficient tuning of the selectivity of
      the catalysts. By employment of the different enantiomeric forms of the
      catalysts, both enantiomers of the homoallylic amines could be selectively
      obtained. Both allyl stannanes and allyl trifluoroborates can be employed as
      allyl sources in the reactions. The biphenanthrol-based complexes gave higher
      selectivity than the substituted BINOL-based analogues, probably because of the
      well-shaped chiral pocket generated by employment of the biphenanthrol complexes.
      The enantioselective allylation of sulfonimines presented in this study has
      important implications for the mechanism given for the pincer complex-catalyzed
      allylation reactions, confirming that this process takes place without
      involvement of palladium(0) species.

PMID- 17523663
TI  - Chemical and structural implications of 1',2'- versus 2',4'- conformational
      constraints in the sugar moiety of modified thymine nucleosides.
AB  - In order to understand how the chemical nature of the conformational constraint
      of the sugar moiety in ON/RNA(DNA) dictates the duplex structure and reactivity,
      we have determined molecular structures and dynamics of the conformationally
      constrained 1',2'-azetidine- and 1',2'-oxetane-fused thymidines, as well as their
      2',4'-fused thymine (T) counterparts such as LNA-T, 2'-amino LNA-T, ENA-T, and
      aza-ENA-T by NMR, ab initio (HF/6-31G** and B3LYP/6-31++G**), and molecular
      dynamics simulations (2 ns in the explicit aqueous medium). It has been found
      that, depending upon whether the modification leads to a bicyclic 1',2'-fused or
      a tricyclic 2',4'-fused system, they fall into two distinct categories
      characterized by their respective internal dynamics of the glycosidic and the
      backbone torsions as well as by characteristic North-East type sugar conformation
      (P = 37 degrees +/- 27 degrees , phi(m) = 25 degrees +/- 18 degrees ) of the
      1',2'-fused systems, and (ii) pure North type (P = 19 degrees +/- 8 degrees ,
      phi(m) = 48 degrees +/- 4 degrees ) for the 2',4'-fused nucleosides. Each group
      has different conformational hyperspace accessible, despite the overall
      similarity of the North-type conformational constraints imposed by the 1',2'- or
      2',4'-linked modification. The comparison of pK(a)s of the 1-thyminyl aglycon as
      well as that of endocyclic sugar-nitrogen obtained by theoretical and
      experimental measurements showed that the nature of the sugar conformational
      constraints steer the physicochemical property (pK(a)) of the constituent 1
      thyminyl moiety, which in turn can play a part in tuning the strength of hydrogen
      bonding in the basepairing.

PMID- 17523664
TI  - Novel functionalizations of [60]fullerene-fused lactones.
AB  - Reactions of [60]fullerene-fused lactones with methylmagnesium bromide and
      diisobutylaluminum hydride afforded rare fullerene hemiketals and hemiacetals,
      which were dehydrated by p-toluenesulfonic acid monohydrate or polyphosphonic
      acid to the corresponding [60]fullerene-fused dihydrofurans. Thus obtained alkyl
      substituted and especially unsubstituted [60]fullerene-fused dihydrofurans are
      difficult to prepare by other methods. The unsubstituted [60]fullerene-fused
      lactone could react with aliphatic amines to give fullerols.

PMID- 17523665
TI  - Synthesis of [60]fullerene acetals and ketals: reaction of [60]fullerene with
      aldehydes/ketones and alkoxides.
AB  - The reaction of C(60) with propionaldehyde (butyraldehyde or phenylacetaldehyde)
      and MeONa-MeOH or EtONa-EtOH in anhydrous chlorobenzene in the presence of air at
      room temperature unexpectedly gave rare fullerene acetals 2aa-cb, while the
      reaction of C(60) with acetone (acetophenone, cyclohexanone, or cyclopentanone)
      and MeONa-MeOH or EtONa-EtOH under the same conditions afforded the uncommon
      fullerene ketals 4aa-db. A possible reaction mechanism for the formation of the
      fullerene acetals and ketals is proposed based on further experimental results.

PMID- 17523666
TI  - Excited-state intramolecular proton transfer in 2-(2'
      arylsulfonamidophenyl)benzimidazole derivatives: the effect of donor and acceptor
      substituents.
AB  - A series of water-soluble 2-(2'-arylsulfonamidophenyl)benzimidazole derivatives
      containing electron-donating and accepting groups attached to various positions
      of the fluorophore pi-system has been synthesized and characterized in aqueous
      solution at 0.1 M ionic strength. The measured pK(a)'s for deprotonation of the
      sulfonamide group of monosubstituted derivatives range between 6.75 and 9.33 and
      follow closely Hammett's free energy relationship. In neutral aqueous buffer, all
      compounds undergo efficient excited-state intramolecular proton transfer (ESIPT)
      to yield a strongly Stokes-shifted fluorescence emission from the phototautomer.
      Upon deprotonation of the sulfonamide nitrogen at high pH, ESIPT is interrupted
      to yield a new, blue-shifted emission band. The peak absorption and emission
      energies were strongly influenced by the nature of the substituents and their
      attachment positions on the fluorophore pi-system. The fluorescence quantum yield
      of the ESIPT tautomers revealed a significant correlation with the observed
      Stokes shifts. The study provides valuable information regarding substituent
      effects on the photophysical properties of this class of ESIPT fluorophores in an
      aqueous environment and may offer guidelines for designing emission ratiometric
      pH or metal-cation sensors for biological applications.

PMID- 17523667
TI  - Aminolysis of Y-substituted phenyl X-substituted cinnamates and benzoates: effect
      of modification of the nonleaving group from benzoyl to cinnamoyl.
AB  - A kinetic study is reported for reactions of Y-substituted phenyl X-substituted
      cinnamates (1a-e and 3a-g) and benzoates (2a-e and 4a-g) with a series of
      alicyclic secondary amines in 80 mol % H2O/20 mol % DMSO at 25.0 +/- 0.1 degrees
      C. Reactions of 2,4-dinitrophenyl X-substituted cinnamates (1a-e) and benzoates
      (2a-e) with amines result in linear Yukawa-Tsuno plots. The rho(X) values are
      much smaller for the reactions of 1a-e than for those of 2a-e. A distance effect
      and the nature of the reaction mechanism (i.e., a concerted mechanism for 1a-e)
      have been suggested to be responsible for the small rho(X) values. The Bronsted
      type plots for the reactions of 2,4-dinitrophenyl X-substituted cinnamates (1a,
      1c, and 1e) with amines are curved with a decreasing betanuc value from 0.65 to
      0.3-0.4. The reactions of Y-substituted phenyl cinnamates (3a-g) with morpholine
      also result in a curved Bronsted plot, while the corresponding reactions of Y
      substituted phenyl benzoates (4a-e) exhibit a linear Bronsted plot. It has been
      concluded that the curved Bronsted plots found for the reactions of the
      cinnamates (1a, 1c, 1e, and 3a-g) are not due to a change in the rate-determining
      step (RDS) but due to a normal Hammond effect for a concerted mechanism, that is,
      an earlier transition state (TS) for a more reactive amine or substrate.

PMID- 17523668
TI  - Synthesis of 2-substituted-5-halo-2,3-dihydro-4(H)-pyrimidin-4-ones and their
      derivatization utilizing the Sonogashira coupling reaction in the
      enantioselective synthesis of alpha-substituted beta-amino acids.
AB  - A convenient, one-pot procedure for the synthesis of 1-benzoyl-2(S)-substituted-5
      iodo-2,3-dihydro-4(H)-pyrimidin-4-ones by tandem decarboxylation/beta-iodination
      of the corresponding 6-carboxy-perhydropyrimidin-4-ones was developed. In
      addition, several 1-benzoyl-2(S)-substituted-5-bromo-2,3-dihydro-4(H)-pyrimidin-4
      ones were readily prepared by bromination of 1-benzoyl-2(S)-substituted-2,3
      dihydro-4(H)-pyrimidin-4-ones. Subsequently, Sonogashira coupling of the
      halogenated heterocyclic enones with various terminal alkynes produced 1-benzoyl
      2(S)-isopropyl-5-alkynyl-2,3-dihydro-4(H)-pyrimidin-4-ones in good yields.
      Hydrogenation of the unsaturated C-C moieties in the Sonogashira products
      followed by acid hydrolysis afforded highly enantioenriched alpha-substituted
      beta-amino acids.

PMID- 17523669
TI  - Mitsunobu coupling of nucleobases and alcohols: an efficient, practical synthesis
      for novel nonsugar carbon nucleosides.
AB  - A simple facile synthesis of substituted purine derivatives has been developed by
      using Mitsunobu conditions for an alcohol and a respective nucleobase. A wide
      range of alcohols produces good to excellent yield (>90%). The resulting purine
      analogues show good regioselectivity with N-9 substitution as the dominant
      products in most of the cases. Application of diastereospecific alcohols reveals
      a complete inversion of the carbon stereogenic center giving a single
      diastereomer. More than two dozen novel nucleobase derivatives have been prepared
      in high yield.

PMID- 17523670
TI  - Formation of diethyl 2-amino-1-cyclopentenylphosphonates: a simple synthesis with
      a unique mechanism.
AB  - Reaction of diethyl 5-chloro-1-pentynylphosphonate with primary and secondary
      amines produces novel 2-amino-1-cyclopentenylphosphonates, 1, in excellent
      isolated yields (79-88%). Calculations supported by experimental facts point to a
      two-step mechanism: an initial amine addition to give a zwitterionic intermediate
      followed by cyclization and proton transfer. Calculations rule out the formation
      of an enamine as an intermediate.

PMID- 17523671
TI  - Structural distortions and dynamic behavior of the elusive "L"-shaped cis
      bicyclo[3.3.0]octenyllithium: X-ray crystallographic and NMR studies.
AB  - Substituted cis-bicyclo[3.3.0]octenyllithium prepared by addition of t-BuLi to 3
      methylene-1,4-cyclooctadiene in the presence of TMEDA crystallizes as a dimer
      with one unsolvated Li(+) sandwiched between the external faces of two allyl
      anions in a triple ion, and external to it the second Li(+) is bidentately
      complexed to TMEDA, 8. Within each allyl unit, the allyl bonds have different
      lengths, and all four rings deviate from coplanarity which relieves strain in the
      rings despite introducing partial localization of the allyl anions. A similar
      structure prevails in solution as shown by (7)Li NMR and the results of
      (7)Li{(1)H} HOESY and (1)H, (1)H NOESY experiments. Carbon-13 NMR line shape
      changes indicate that the system undergoes a fast allyl bond shift concerted with
      conformation shifts of the out of plane carbons, ca. DeltaG = 9 kcal x mol(-1).
      Cyclopentyllithium prepared by CH(3)Li cleavage of the trimethylstannyl
      derivative slowly undergoes an allowed ring opening to pentadienyllithium as well
      as deprotonating the solvent. The different behavior of dienylic lithium species
      is attributed to the relative separation of their termini.

PMID- 17523672
TI  - TMSCH(2)Li and TMSCH(2)Li-LiDMAE: efficient reagents for noncryogenic halogen
      lithium exchange in bromopyridines.
AB  - TMSCH(2)Li and TMSCH(2)Li-LiDMAE have been used efficiently for bromine-lithium
      exchange in 2-bromo-, 3-bromo-, and 2,5-dibromopyridines under noncryogenic
      conditions, while low temperatures (-78 to -100 degrees C) are always needed with
      n-BuLi. The aminoalkoxide LiDMAE induced a remarkable C-2 selectivity with 2,5
      dibromopyridines in toluene at 0 degrees C, which was unprecedented at such a
      temperature. The lithiopyridines were successfully reacted with electrophiles
      also under noncryogenic conditions giving the expected adducts in good yields.

PMID- 17523673
TI  - Asymmetric alpha-alkynylation of piperidine via N-sulfinyliminium salts.
AB  - Piperidine was stereoselectively alpha-alkynylated in a four-step sequence made
      up of transformation to a chiral nonracemic N-sulfinylpiperidine, anodic
      oxidation to N-sulfinyliminium ion equivalent, alkynylation through addition of a
      mixed organoaluminum derivative, and final acidic deprotection of the sulfoxide.
      Overall yields are around 50%, and the diastereoselectivity of the nucleophilc
      addition was between 92 and 99% de, allowing isolation of the final product with
      99% enantiomeric purity.

PMID- 17523674
TI  - Expedient syntheses of antofine and cryptopleurine via intramolecular 1,3-dipolar
      cycloaddition.
AB  - The practical and expedient total syntheses of the representative
      phenanthroindolizidine and phenanthroquinolizidine alkaloids, antofine and
      cryptopleurine, are described. Construction of the pyrrolidine and piperidine
      ring of each alkaloid was achieved by using an intramolecular 1,3-dipolar
      cycloaddition of an azide onto an alkene and subsequent reduction of the
      resulting imine and aziridine.

PMID- 17523676
TI  - Pyrroloquinoline quinone biogenesis: characterization of PqqC and its H84N and
      H84A active site variants.
AB  - Pyrroloquinoline quinone [4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9
      tricarboxylic acid (PQQ)] is a bacterial vitamin that serves as a cofactor in
      numerous alcohol dehydrogenases. Its biosynthesis in Klebsiella pneumoniae is
      facilitated by six genes, pqqABCDEF, and proceeds by an unknown pathway. The
      protein encoded by pqqC catalyzes the final step of PQQ formation, which involves
      a ring closure and an overall eight-electron oxidation of 3a-(2-amino-2
      carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid
      (AHQQ) in the absence of a redox-active metal or cofactor. A recent crystal
      structure has implicated numerous PQQ-PqqC interactions [Magnusson et al. (2004)
      Proc. Natl. Acad. Sci. U.S.A. 101, 7913-7918]. To investigate the mechanism of
      the PqqC reaction, the active site residue His84 has been mutated to H84A and
      H84N, and the kinetic and spectroscopic properties have been compared to each
      other and the wild-type enzyme using aerobic and anaerobic conditions. Both
      mutants form PQQ under aerobic conditions with rate constants of 0.09 min-1 and
      0.056 min-1 relative to 0.34 min-1 for the wild-type enzyme. In addition to the
      initial E-AHQQ complex (532-536 nm) and the product E-PQQ complex (346-366 nm), a
      number of spectral intermediates are observed between 316 and 344 nm. The
      anaerobic reaction is particularly informative, showing that while mixing of H84N
      with AHQQ leads to a 344 nm intermediate, this is unable to proceed to a final
      318 nm species; by contrast H84A forms the 344 nm species as a precursor to the
      318 nm species. In the context of the proposed chemical mechanism for PqqC
      [Magnusson et al. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 7913-7918], we assign
      the 344 nm intermediate to a quinoid species and the 318 nm intermediate to an
      initial quinol species. The proposed role of H84 is as a proton donor to the
      oxyanion of the quinoid species such that subsequent C-H bond cleavage can occur
      to form a monoanionic quinol. In the absence of a proton donor (as occurs in
      H84N), the normal reaction path is precluded as this would require formation of
      an unstable, dianionic species. Unlike H84N, H84A appears to be small enough to
      allow entry of active site water, which is postulated to adopt the role of active
      site proton donor.

PMID- 17523677
TI  - Effects of surface adsorption on catalytic activity of heavy meromyosin studied
      using a fluorescent ATP analogue.
AB  - Biochemical studies in solution and with myosin motor fragments adsorbed to
      surfaces (in vitro motility assays) are invaluable for elucidation of actomyosin
      function. However, there is limited understanding of how surface adsorption
      affects motor properties, e.g., catalytic activity. Here we address this issue by
      comparing the catalytic activity of heavy meromyosin (HMM) in solution and
      adsorbed to standard motility assay surfaces [derivatized with
      trimethylchlorosilane (TMCS)]. For these studies we first characterized the
      interaction of HMM and actomyosin with the fluorescent ATP analogue adenosine 5'
      triphosphate Alexa Fluor 647 2'- (or 3'-) O-(N-(2-aminoethyl)urethane)
      hexa(triethylammonium) salt (Alexa-ATP). The data suggest that Alexa-ATP is
      hydrolyzed by HMM in solution at a slightly higher rate than ATP but with a
      generally similar mechanism. Furthermore, Alexa-ATP is effective as a fuel for
      HMM-propelled actin filament sliding. The catalytic activity of HMM on TMCS
      surfaces was studied using (1) Alexa-ATP in total internal reflection
      fluorescence (TIRF) spectroscopy experiments and (2) Alexa-ATP and ATP in HPLC
      aided ATPase measurements. The results support the hypothesis of different HMM
      configurations on the surface. However, a dominant proportion of the myosin heads
      were catalytically active, and their average steady-state hydrolysis rate was
      slightly higher (with Alexa-ATP) or markedly higher (with ATP) on the surface
      than in solution. The results are discussed in relation to the use of TMCS
      surfaces and Alexa-ATP for in vitro motility assays and single molecule studies.
      Furthermore, we propose a novel TIRF microscopy method to accurately determine
      the surface density of catalytically active myosin motors.

PMID- 17523678
TI  - DNA binding, annealing, and strand exchange activities of Brh2 protein from
      Ustilago maydis.
AB  - Brh2 is the Ustilago maydis ortholog of the BRCA2 tumor suppressor. It functions
      in repair of DNA by homologous recombination by controlling the action of Rad51.
      A critical aspect in the control appears to be the recruitment of Rad51 to single
      stranded DNA regions exposed as lesions after damage or following a disturbance
      in DNA synthesis. In previous experimentation, Brh2 was shown to nucleate
      formation of the Rad51 nucleoprotein filament that becomes the active element in
      promoting homologous pairing and DNA strand exchange. Nucleation was found to be
      initiated at junctions of double-stranded and single-stranded DNA. Here we
      investigated the DNA binding specificity of Brh2 in more detail using
      oligonucleotide substrates. We observed that Brh2 prefers partially duplex
      structures with single-stranded branches, flaps, or D-loops. We found also that
      Brh2 has an inherent ability to promote DNA annealing and strand exchange
      reactions on free as well as RPA-coated substrates. Unlike Rad51, Brh2 was able
      to promote DNA strand exchange when preincubated with double-stranded DNA. These
      findings raise the notion that Brh2 may have roles in homologous recombination
      beyond the previously established Rad51 mediator activity.

PMID- 17523679
TI  - The conversion of vitamin K epoxide to vitamin K quinone and vitamin K quinone to
      vitamin K hydroquinone uses the same active site cysteines.
AB  - Vitamin K epoxide (or oxido) reductase (VKOR) is the target of warfarin and
      provides vitamin K hydroquinone for the carboxylation of select glutamic acid
      residues of the vitamin K-dependent proteins which are important for coagulation,
      signaling, and bone metabolism. It has been known for at least 20 years that
      cysteines are required for VKOR function. To investigate their importance, we
      mutated each of the seven cysteines in VKOR. In addition, we made VKOR with both
      C43 and C51 mutated to alanine (C43A/C51A), as well as a VKOR with residues C43
      C51 deleted. Each mutated enzyme was purified and characterized. We report here
      that C132 and C135 of the CXXC motif are essential for both the conversion of
      vitamin K epoxide to vitamin K and the conversion of vitamin K to vitamin K
      hydroquinone. Surprisingly, conserved cysteines, 43 and 51, appear not to be
      important for either reaction. For the in vitro reaction driven by
      dithiothreitol, the 43-51 deletion mutation retained 85% and C43A/C51A 112% of
      the wild-type activity. The facile purification of the nine different mutations
      reported here illustrates the ease and reproducibility of VKOR purification by
      the method reported in our recent publication [Chu, P.-H., Huang, T.-Y.,
      Williams, J., and Stafford, D. W. (2006) Proc. Natl. Acad. Sci. U S A. 103, 19308
      19313].

PMID- 17523680
TI  - Role of solution chemistry and ion valence on the adhesion kinetics of
      groundwater and marine bacteria.
AB  - The role of solution chemistry on bacterial adhesion has been investigated using
      a radial stagnation point flow (RSPF) system. This experimental system utilized
      an optical microscope and an image-capturing device to directly observe the
      deposition kinetics of a groundwater bacterium, Burkholderia cepacia G4g, and a
      marine bacterium, Halomonas pacifica g. Experiments were carried out under well
      controlled hydrodynamic and solution chemistry conditions, allowing for the
      sensitivity of bacterial adhesion behavior to be examined under a range of ionic
      strength and valence (KCl vs CaCl2) simulating groundwater and marine
      environments. Complimentary cell characterization techniques were conducted to
      evaluate the electrophoretic mobility, hydrophobicity, surface charge density,
      and viability of the bacteria under the same range of conditions. Solution
      chemistry was found to have a marked effect on the electrokinetic and surface
      properties of bacteria and the quartz collector, as well as on the resulting rate
      of bacterial deposition. Comparable adhesion trends were observed for B. cepacia
      G4g and H. pacifica g. Specifically, the deposition rates of the two bacteria
      species in both KCl and CaCl2 solutions increased with ionic strength, a trend
      consistent with traditional Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, which
      considers the combination of van der Waals and electrostatic double-layer
      interaction forces. However, in some cases, experimental results showed bacterial
      deposition behavior to deviate from DLVO predictions. On the basis of the
      systematic investigation of bacterial cell characteristics, it was found that
      Ca2+ ions play a distinct role on bacterial surface charge, hydrophobicity, and
      deposition behaviors. It is further suggested that bacterial adhesion is
      determined by the combined influence of DLVO interactions, electrosteric
      interactions associated with solution chemistry, and the hydrodynamics of the
      deposition system.

PMID- 17523681
TI  - Effect of water on foaming properties of diglycerol fatty acid ester-oil systems.
AB  - We have studied the effect of added water on the nonaqueous foaming properties of
      diglycerol fatty acid ester nonionic surfactant systems. Diglycerol monomyristate
      (designated as DGM) could not foam in nonpolar oils squalane and hexadecane at
      normal room temperature. Nevertheless, addition of a small amount of water
      induces a dramatic change in foaming properties. Both the foamability and foam
      stability increases with the amount of added water within the studied
      concentration range. Phase behavior study showed that in the dilute regions there
      is dispersion of solid surfactant in the aforementioned oils in the DGM systems.
      The particle size of the dispersed solid phase was found to be several tens of
      microns in the water free system, and hence it tends to coagulate and
      precipitate. In the case of shorter alkyl chain length, diglycerol monolaurate
      (DGL) surfactant-oil systems, dispersion of lamellar liquid crystal (Lalpha) is
      observed at room temperature, and the poor foaming properties were attributed to
      the large particle size of the liquid crystal. In both the DGL and DGM-oil
      systems, we observed a tendency of the particle size to decrease with the
      increasing concentration of added water. At higher temperature, the solid
      surfactant transforms to lamellar liquid crystal phase, and foaming is improved
      in the DGM/squalane system. Foams are stable for several minutes. Judging from
      the foaming test and particle size distribution data it can be concluded that the
      poor foaming in the diglycerol fatty acid esters-oil systems may possibly be due
      to bigger particle size, which causes precipitation. Addition of water results in
      the dispersion of smaller particles and improves the foaming behavior.

PMID- 17523682
TI  - Electric-field-driven surface aggregation of a model zwitterionic surfactant.
AB  - Electrochemical measurements, atomic force microscopy, and scanning tunneling
      microscopy have been combined to describe the electric-field-controlled surface
      aggregation of N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (DDAPS), a
      model zwitterionic surfactant, at a Au(111) electrode surface. At concentrations
      below the critical micelle concentration (CMC), the monomer adsorbs and
      aggregates at the surface. The charge on the metal (sigmaM) controls the
      orientation of adsorbed molecules and consequently the film structure. At high
      negative (sigmaM < -5 microC cm-2) charge densities, a spongy, disordered film is
      formed in which the polar heads are turned toward the solution. At high positive
      (sigmaM > +5 microC cm-2) charge densities, a planar film with "blisters" is
      observed with the polar heads of DDAPS turned to the metal. Hemicylindrical
      aggregates are observed in the intermediate charge density range (-5 < sigmaM <
      +5 microC cm-2). At bulk concentrations higher than the CMC, micelles adsorb and
      the structure of these films is controlled by the fusion of the adsorbed
      micelles. STM and AFM images provided direct visualization of this field-driven
      surface aggregation of the zwitterionic surfactant.

PMID- 17523683
TI  - Transparent superhydrophobic films based on silica nanoparticles.
AB  - We demonstrate a layer-by-layer processing scheme that can be utilized to create
      transparent superhydrophobic films from SiO2 nanoparticles of various sizes. By
      controlling the placement and level of aggregation of differently sized
      nanoparticles within the resultant multilayer thin film, it is possible to
      optimize the level of surface roughness to achieve superhydrophobic behavior with
      limited light scattering. Transparent superhydrophobic films were created by the
      sequential adsorption of silica nanoparticles and poly(allylamine hydrochloride).
      The final assembly was rendered superhydrophobic with silane treatment. Optical
      transmission levels above 90% throughout most of the visible region of the
      spectrum were realized in optimized coatings. Advancing water droplet contact
      angles as high as 160 degrees with low contact angle hysteresis (<10 degrees )
      were obtained for the optimized multilayer thin films. Because of the low
      refractive index of the resultant porous multilayer films, they also exhibited
      antireflection properties.

PMID- 17523684
TI  - Cholesterol/phospholipid interactions in hybrid bilayer membranes.
AB  - The interactions between cholesterol and saturated phospholipids in hybrid
      bilayer membranes (HBMs) were investigated using the interface-sensitive
      technique of vibrational sum frequency spectroscopy (VSFS). The unique
      sensitivity of VSFS to order/disorder transitions of the lipid acyl chains was
      used to determine the main gel to liquid crystal phase transition temperature,
      Tm, for HBMs of binary cholesterol/phospholipid mixtures on octadecanethiolate
      self-assembled monolayers. The phase transition temperature and the breadth of
      the transition were shown to increase with cholesterol content, and the phase
      boundaries observed in the cholesterol/phospholipid HBMs were comparable to the
      published phase diagrams of binary cholesterol/phospholipid vesicles. A
      thermodynamic assessment of the cooperative units of the HBM phase transitions
      revealed the presence of <10 nm diameter domains that were independent of the
      cholesterol composition.

PMID- 17523685
TI  - Cellulose acetate-directed growth of bamboo-raft-like single-crystalline selenium
      superstructures: high-yield synthesis, characterization, and formation mechanism.
AB  - High-yield synthesis of bamboo-raft-like single-crystalline selenium
      superstructures has been realized for the first time via a facile solvothermal
      approach by reducing SeO2 with ethylene alcohol in the presence of cellulose
      acetate. The formation of a raftlike superstructure with various forms is
      strongly dependent on the temperature, amount of cellulose acetate, reaction
      time, and even preheating treatment. The suitable amount of cellulose acetate is
      essential for the formation of elegant and uniform raft Se. The morphology,
      microstructure, optical properties, and chemical compositions of bamboo-raft-like
      selenium were characterized using various techniques (X-ray diffraction, field
      emission scanning electron microscopy, transmission electron microscopy (TEM),
      high-resolution (HR) TEM, X-ray photoelectron spectroscopy, UV-vis spectroscopy,
      FTIR spectroscopy, and Raman spectroscopy). A possible growth mechanism has been
      proposed. Such special superstructures could provide a useful precursor for
      potential applications.

PMID- 17523686
TI  - Dissociative adsorption of NO on TiO2 (110)-(1 x 2) surface: Ti2O3 rows as
      actives sites for the adsorption.
AB  - The interaction of NO with TiO2 (110)-(1 x 2) surface has been studied by X-ray
      photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, Auger
      electron spectroscopy, and low-energy electron diffraction, with the aim to
      clarify the role of ordered defects in NO reactivity toward TiO2. The interaction
      was studied for exposures up to 2000 L. However, the main effects occur already
      in the first 2 L. The exposure of the surfaces to NO resulted in the healing of
      defect sites without adsorption of N and low-energy electron diffraction shows
      that the surface (1 x 2) symmetry is not lost after the NO dose.

PMID- 17523687
TI  - Specific interactions improve the loading capacity of block copolymer micelles in
      aqueous media.
AB  - Block copolymer micelles find application in many fields as nanocarriers,
      especially in drug delivery. We report herein that specific interactions between
      hydrophobic guest molecules and core-forming segments can significantly improve
      the loading capacity of polymeric micelles. High loading capacities (>100%
      weight/weight of polymer (w/wp)) were systematically observed for the
      encapsulation of probes containing weak carboxylic acid groups by micellar
      nanoparticles having poly[2-(dialkylamino)ethyl methacrylate] cores (i.e.,
      particles whose cargo space exhibits antagonist weak base functions), as
      demonstrated by the incorporation of indomethacin (IND), ibuprofen (IBPF), and
      trans-3,5-bis(trifluoromethyl)cinnamic acid (F-CIN) into either poly(ethylene
      oxide)-b-poly[2-(diisopropylamino)ethyl methacrylate] (PEO-b-PDPA) or
      poly(glycerol monomethacrylate)-b-PDPA (PG2MA-b-PDPA) micelles. The
      esterification of IND yielding to a nonionizable IND ethyl ester derivative (IND
      Et) caused an abrupt decrease in the micellar loading capacity down to 10-15%
      w/wp. Similar results were also obtained when IND was combined with nonionizable
      block copolymers such as PEO-b-polycaprolactone (PEO-b-PCL) and PEO-b
      poly(glycidyl methacrylate) (PEO-b-PGMA). The existence of acid-base interactions
      between the solubilizate and the weak polybase block forming the micelle core was
      confirmed by 1H NMR measurements. However, the incorporation of high numbers of
      hydrophobic guest molecules inside polymeric micelles can provoke not only an
      increase in the hydrodynamic size (2RH) of the objects but also a substantial
      change in the morphology (transition from spheres to cylinders). The application
      of the Higuchi model showed that the probe release followed a diffusion
      controlled mechanism, and diffusion coefficients (D) on the order of 10-18-10-17
      cm2/s were determined for IND release from 1.0 mg/mL PEO113-b-PDPA50 + 100% w/wp
      IND. Probe release from micelles with weak polybase-based cores can also be
      triggered by changes in the solution pH.

PMID- 17523688
TI  - Cholesterol biosensor based on amino-undecanethiol self-assembled monolayer using
      surface plasmon resonance technique.
AB  - Cholesterol oxidase has been covalently immobilized onto 11-amino-1-undecanethiol
      hydrochloride (AUT) self-assembled monolayer (SAM) fabricated on gold (Au)
      substrates using glutaraldehyde as a cross-linker. These ChOx/AUT/Au
      bioelectrodes characterized using contact angle (CA) measurements;
      electrochemical technique and atomic force microscopy (AFM) have been utilized
      for the estimation of cholesterol in solution using the surface plasmon resonance
      (SPR) technique. These biosensing electrodes exhibiting linearity from 50 to 500
      mg/dL of cholesterol in solution and sensitivity of 1.23 m0/(mg dL), can be used
      more than 20 times and have a shelf life of about 10 weeks when stored at 4
      degrees C.

PMID- 17523689
TI  - Wormlike micelle formation and flow alignment of a pluronic block copolymer in
      aqueous solution.
AB  - The self-assembly into wormlike micelles of a poly(ethylene oxide)-b
      poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer Pluronic P84 in
      aqueous salt solution (2 M NaCl) has been studied by rheology, small-angle X-ray
      and neutron scattering (SAXS/SANS), and light scattering. Measurements of the
      flow curves by controlled stress rheometry indicated phase separation under flow.
      SAXS on solutions subjected to capillary flow showed alignment of micelles at
      intermediate shear rates, although loss of alignment was observed for high shear
      rates. For dilute solutions, SAXS and static light scattering data on unaligned
      samples could be superposed over three decades in scattering vector, providing
      unique information on the wormlike micelle structure over several length scales.
      SANS data provided information on even shorter length scales, in particular,
      concerning "blob" scattering from the micelle corona. The data could be modeled
      based on a system of semiflexible self-avoiding cylinders with a circular cross
      section, as described by the wormlike chain model with excluded volume
      interactions. The micelle structure was compared at two temperatures close to the
      cloud point (47 degrees C). The micellar radius was found not to vary with
      temperature in this region, although the contour length increased with increasing
      temperature, whereas the Kuhn length decreased. These variations result in an
      increase of the low-concentration radius of gyration with increasing temperature.
      This was consistent with dynamic light scattering results, and, applying
      theoretical results from the literature, this is in agreement with an increase in
      endcap energy due to changes in hydration of the poly(ethylene oxide) blocks as
      the temperature is increased.

PMID- 17523692
TI  - Effects of catalyst introduction methods using PAMAM dendrimers on selective
      electroless nickel deposition on polyelectrolyte multilayers.
AB  - We studied the effects of catalyst introduction methods using poly(amidoamine)
      (PAMAM) dendrimers on the nickel patterning of polyelectrolyte multilayer (PEM)
      coated substrates. Three different approaches to palladium catalyst introduction
      using microcontact printing as the patterning technique were utilized and
      compared. The catalyst introduction methods are (1) direct catalyst stamping, (2)
      directed assembly using PAMAM dendrimer stamping, and (3) catalyst encapsulation
      and reduction to nanoparticles within PAMAM dendrimers before stamping. After
      patterning, the sample surfaces were placed in an electroless bath where nickel
      was selectively plated onto the patterns. The patterned surfaces were
      characterized using optical microscopy, atomic force microscopy, scanning
      electron microscopy, and energy-dispersive X-ray spectroscopy. The metal plating
      rates on different homogeneous surfaces that simulate the patterned surfaces were
      measured using a quartz crystal microbalance. In addition, the effect of PEM film
      thickness (i.e., number of bilayers) on the selectivity of nickel patterning was
      investigated.

PMID- 17523691
TI  - Adhesion plaque formation dynamics between polymer vesicles in the limit of
      highly concentrated binding sites.
AB  - This work examines the process of adhesion plaque formation between pairs of
      copolymer vesicles presenting dense surface concentrations of avidin
      (NeutrAvidin) and biotin. Micropipet aspiration maintains constant membrane
      tension, as the low-tension vesicle membrane spreads over a second, more tensed
      vesicle. Spreading rates near 1 microm/s but as high as 7 microm/s (the adhesion
      plaque diameter) and contact angle growth rates of 2-14 deg/s are observed. The
      ultimate contact angles, in the range of 120-140 degrees, are independent of
      membrane tension and also exceed those previously reported. Adhesion plaque
      formation occurs in three phases: an initial step in which contact is
      established, typically lasting from a few seconds to a minute, an abrupt jump
      into contact in which both vesicles undergo substantial deformation, and a slower
      continued growth of the contact angle and area. Vesicle pairs are irreversibly
      bound at the plaque such that attempts to peel them apart cause membrane rupture
      at critical tensions as high as 4 mN/m, setting a lower bound on the interfacial
      strength. When the quantity tau(1 - cos theta) (with tau the membrane tension and
      theta the contact angle) is plotted as a function of time during plaque formation
      for different values of tau, the curves fail to collapse, indicating the chemical
      driving force for adhesion greatly exceeds the mechanical resisting tension.

PMID- 17523690
TI  - Effects of lipid confinement on insulin stability and amyloid formation.
AB  - We report on a study of insulin incorporation into cubic phases of mono-olein
      (MO), using synchrotron small-angle X-ray scattering and FT-IR spectroscopy. We
      studied the thermal stability and aggregation scenario of insulin as a function
      of protein concentration in the narrow water channels of the cubic lipid matrix
      and compared it with data for insulin unfolding and fibrillation in bulk water
      solutions. The concomitant effect of insulin entrapment on the structure and
      phase behavior of the lipid matrix itself was also examined. We show that the
      protein's unfolding behavior and stability are influenced by confinement due to
      geometrical limitations, and vice versa, the topological properties of the lipid
      matrix change as well. The addition of insulin already at concentrations as low
      as 0.1 wt % significantly alters the phase behavior of MO. Surprisingly, new
      cubic structures are induced by insulin incorporation into the lipid matrix. When
      insulin begins to partially unfold at higher temperatures, the structure of the
      new cubic phase changes and finally disappears around 60 degrees C, where the
      aggregation process sets in. The aggregation in cubo proceeds much faster and
      leads to the formation of medium-sized oligomers or clusters, while the formation
      of large fibrillar agglomerates, as observed for bulk insulin aggregation, is
      largely prohibited. Hence, the results yield valuable information about the use
      of cubic mesoporous lipid systems as a medium for long-term storage of insulin
      and aggregation-prone proteins in general. Furthermore, the results provide new
      insights into the effects of soft-matter confinement on protein aggregation and
      fibrillation, a situation usually met in natural cell environments.

PMID- 17523693
TI  - Drug-induced nephrotoxicity in children: pharmacologically based prevention of
      long-term impairment.

PMID- 17523695
TI  - Potential of gene expression profiling in the management of childhood acute
      lymphoblastic leukemia.
AB  - Childhood acute lymphoblastic leukemia (ALL) is a heterogeneous disease. Current
      treatment approaches are tailored according to the clinical features of the host,
      genotypic features of the leukemic blast, and early response to therapy. Although
      these approaches have been successful in dramatically improving outcomes,
      approximately 20% of children with ALL still relapse and many of these children
      do not have an identifiable adverse risk factor at presentation. Further insights
      into the biologic basis of the disease may contribute to novel, rational
      treatment strategies. Childhood ALL has served as an example for demonstrating
      the feasibility and potential of high-throughput technologies such as global gene
      expression or transcript profiling. In the last decade or so, utilization of
      these techniques has grown exponentially. As the methodology undergoes refinement
      and validation, it is plausible that microarrays may be used in the routine
      management of childhood ALL in the next few years. This article discusses the
      numerous applications to date of gene expression profiling in childhood ALL.
      Multiple investigators have made it evident that microarrays can be used as a
      single platform for the accurate classification of ALL into the various
      cytogenetic subtypes. Additional promising utilities include prediction of early
      response to therapy, overall outcome, and adverse effects. Identification of
      patients who are predicted to have an unfavorable outcome may allow for early
      intervention such as intensification of therapy or avoidance of drugs that are
      associated with specific secondary effects such as therapy-related acute
      myelogenous leukemia. Knowledge has been gained into pathways contributing to
      leukemogenesis and chemoresistance. Therapeutic targets have been identified,
      some of which are entering clinical trials following validation in additional
      preclinical models. These newer methods of genome analyses complemented by
      studies involving the proteome as well as host polymorphisms will have a profound
      impact on the diagnosis and management of childhood ALL.

PMID- 17523696
TI  - Food Intolerance and childhood asthma: what is the link?
AB  - Food allergies and asthma are increasing worldwide. It is estimated that
      approximately 8% of children aged <3 years have food allergies. Foods can induce
      a variety of IgE-mediated, cutaneous, gastrointestinal, and respiratory
      reactions. The most common foods responsible for allergic reactions in children
      are egg, milk, peanut, soy, fish, shellfish, and tree nuts. Asthma alone as a
      manifestation of a food allergy is rare and atypical. Less than 5% of patients
      experience wheezing without cutaneous or gastrointestinal symptoms during a food
      challenge. In addition to acute respiratory symptoms, a food allergy may also
      induce airway hyper-responsiveness beyond the initial reaction. This process can
      occur in patients who do not demonstrate a decrease in lung function during the
      reaction. Inhalation of aerosolized food particles can cause respiratory symptoms
      in selected food-allergic individuals, particularly with fish and shellfish
      during cooking and aerosolization. However, this has not been demonstrated with
      the smelling of, or casual contact with, peanut butter. Rarely, food additives
      such as sulfating agents can cause respiratory reactions. This reaction occurs
      primarily in patients with underlying asthma, particularly in patients with more
      severe asthma. In contrast, there is no convincing evidence that tartrazine or
      monosodium glutamate can induce asthma responses. Although food-induced asthma is
      rare, it is common for patients and clinicians to perceive that food can trigger
      asthma. Avoidance of specific foods or additives has not been shown to improve
      asthma, even in patients who may perceive that a particular food worsens their
      asthma.However, patients with underlying asthma are more likely to experience a
      fatal or near-fatal food reaction. Food reactions tend to be more severe or life
      threatening when they involve the respiratory tract. The presence of a food
      allergy is a risk factor for the future development of asthma, particularly for
      children with sensitization to egg protein. The diagnosis of a food allergy
      includes skin or in vitro testing as an initial study when the history suggests
      food allergy. While negative testing generally rules out a food allergy, positive
      testing should be followed by a food-challenge procedure for a definitive
      diagnosis. The CAP-RAST FEIA (CAP-radioallergosorbent test [RAST] fluoroenzyme
      immunoasssay system [FEIA]) is an improved in vitro measure that in some cases
      may decrease the need for food challenges. However, similar to skin testing and
      the RAST, there is good sensitivity but poor specificity, such that specific
      challenges are often warranted.

PMID- 17523694
TI  - Delays in immunization have potentially serious health consequences.
AB  - When children are not administered vaccinations according to the recommended
      schedule, they not only fail to receive timely protection from preventable
      diseases at a time when they are most vulnerable, but also increase their risk of
      never fully completing the vaccination course. Both outcomes compromise a
      successful childhood immunization program. Although current data suggest that
      vaccination rates are near 95% for school-aged children in the US, the rate of
      timely vaccination is much lower. A number of large studies have found that the
      majority of children are not currently vaccinated on schedule. Moreover,
      immunization levels for 2- to 3-year-old children have reached a plateau. It is
      essential to recognize that low overall rates of the targeted diseases mask the
      persistent threat they pose if adherence to vaccination schedules declines. A
      delay in one vaccine will produce a domino effect if catch-up adjustments in
      scheduled visits are not implemented aggressively. Published reports have
      demonstrated that failure to adhere to scheduled booster immunizations, not just
      the initial inoculation, results in resurgence of disease. Children fall off the
      vaccination schedule for a variety of reasons. Although many studies suggest that
      inadequate availability to healthcare is not a major determinant of delayed
      immunization, it still factors into parental decisions. Parents should be
      reminded of available healthcare options. From the clinician's end,
      computerization of healthcare records should allow for the generation of
      reminders. It is vital for clinicians to be aware that there are few
      contraindications to vaccination. They should also be prepared to address
      parental concerns regarding the safety of vaccines and should not hesitate to use
      topical analgesics or distraction techniques to facilitate inoculation. With the
      anticipation of several novel vaccines being added to the childhood and
      adolescent immunization schedule in the future, pediatricians face new challenges
      to not only provide every vaccination, but to do so in a timely manner. A lack of
      willingness on the part of the parent, or, occasionally, on the part of the
      clinician, to have multiple vaccines administered to the child during a single
      visit has been shown to be a significant cause of delayed vaccination. Since
      combination vaccines reduce the number of shots that need to be administered, the
      use of combination vaccines may provide the best opportunity to simplify the
      immunization schedule, increasing adherence in the process. Improved adherence to
      established schedules may present a major opportunity to further protect children
      from disease.

PMID- 17523697
TI  - Calcineurin inhibitors in pediatric renal transplant recipients.
AB  - The calcineurin inhibitors, cyclosporine (ciclosporin) [microemulsion] and
      tacrolimus, are the principal immunosuppressants prescribed for adult and
      pediatric renal transplantation. For pediatric patients, both drugs should be
      dosed per body surface area, and pharmacokinetic monitoring is mandatory. While
      monitoring of the trough levels may suffice for tacrolimus, cyclosporine therapy
      that utilizes the microemulsion formulation requires additional monitoring (e.g.
      determination of 2-hour post-dose levels). In a well designed randomized study in
      children, as in studies in adults, there was no difference in short-term patient
      and graft survival with cyclosporine microemulsion and tacrolimus. However,
      tacrolimus was significantly more effective than cyclosporine microemulsion in
      preventing acute rejection after renal transplantation when used in conjunction
      with azathioprine and corticosteroids. With regard to long-term outcome, the
      difference in acute rejection episodes resulted in a better glomerular filtration
      rate at 1 year after transplantation and eventually in better graft survival 4
      years after renal transplantation. Whether this difference persists when
      calcineurin inhibitors are used in combination with mycophenolate mofetil has not
      been determined. The prevalence of hypomagnesemia was higher in the tacrolimus
      group whereas hypertrichosis and gingival hyperplasia occurred more frequently in
      the cyclosporine group. In contrast with adults, the incidence of post
      transplantation diabetes mellitus was not significantly different between
      tacrolimus- and cyclosporine-treated patients. There was also no difference with
      regard to post-transplantation lymphoproliferative disorder. Medication costs
      were similar, but in view of the lower rejection episodes and better long-term
      graft survival as well as the more favorable cosmetic side effect profile,
      tacrolimus may be preferable. The recommendation drawn from the available data is
      that both cyclosporine and tacrolimus can be used safely and effectively in
      children. We recommend that cyclosporine should be chosen when patients
      experience tacrolimus-related adverse events.

PMID- 17523698
TI  - Acute gastroenteritis in children: role of anti-emetic medication for
      gastroenteritis-related vomiting.
AB  - Acute gastroenteritis is associated with significant morbidity in developed
      countries and each year is the cause of death of several million children in
      developing countries. Acute gastroenteritis is usually self-limiting. Oral
      rehydration therapy (ORT) is effective and successful in the majority of
      patients. Vomiting is common at the outset of viral gastroenteritis and can limit
      the effectiveness of ORT. Treatment with newer anti-emetic medications has been
      reported to facilitate ORT and to minimize the risk of dehydration and the need
      for intravenous hydration and hospitalization. The role of anti-emetic
      medications in the treatment of gastroenteritis-related vomiting is not clear.
      Some physicians agree with the use of anti-emetic medications because vomiting is
      unpleasant and distressing for the child and parents alike, and because vomiting
      can increase the likelihood of dehydration, electrolyte imbalance, and the need
      for intravenous hydration or hospitalization. Several surveys have shown that
      anti-emetic medications are commonly prescribed in the treatment of pediatric
      gastroenteritis and that adverse events are uncommon. Efficacy studies of the
      newer anti-emetic medications are now available and reveal that some are
      effective and help facilitate ORT. Other physicians disagree with the use of anti
      emetic medications because acute gastroenteritis is a self-limiting condition,
      vomiting might help rid the body of toxic substances, there was previously a
      relative lack of published evidence of clinical benefit, and there are potential
      adverse events associated with the use of an anti-emetic medication. Anti-emetic
      medications that are currently available include ondansetron, granisetron,
      tropisetron, dolasetron, ramosetron, promethazine, dimenhydrinate,
      metoclopramide, domperidone, droperidol, prochlorperazine, and trimethobenzamide.
      Randomized, placebo-controlled trials suggest that ondansetron is efficacious and
      superior to other anti-emetic medications in the treatment of gastroenteritis
      related vomiting. A recent double-blind clinical trial showed that a single oral
      dose of ondansetron reduces gastroenteritis-related vomiting and facilitates ORT
      without significant adverse events. Ondansetron shows promise as a first-line
      anti-emetic, and judicious use of this agent might increase the success of ORT,
      minimize the need for intravenous therapy and hospitalization, and reduce
      healthcare costs. Ondansetron should be considered in situations where vomiting
      hinders ORT, but a larger randomized, placebo-controlled trial is necessary
      before the medication can be routinely recommended for the treatment of
      gastroenteritis-related vomiting in children.

PMID- 17523699
TI  - Inhaled corticosteroids in children with asthma: pharmacologic determinants of
      safety and efficacy and other clinical considerations.
AB  - The role of inhaled corticosteroids (ICS) in the treatment of childhood asthma
      has been well established. An ideal corticosteroid should demonstrate high
      pulmonary deposition and residency time, in addition to a low systemic
      bioavailability and rapid systemic clearance. The lung depositions of the ICS
      have been compared, with beclomethasone (beclometasone)-hydrofluoroalkane (HFA)
      and ciclesonide showing the highest lung deposition. Lung deposition is
      influenced by not only the inhalation device and type of propellant (HFA or
      chlorofluorocarbon), but also by whether the aerosol is a solution or suspension,
      and the particle size of the respirable fraction. Pulmonary residency time
      increases when budesonide and des-ciclesonide undergo reversible fatty acid
      esterification. The bioavailability of the drug depends on the oral bioavailable
      fraction and the amount absorbed directly from the pulmonary vasculature. The
      clearance rate of des-ciclesonide is very high (228 L/h), increasing its safety
      profile by utilizing extra-hepatic clearance mechanisms. Both des-ciclesonide and
      mometasone have a high protein binding fraction (98-99%). The volume of
      distribution (Vd) is proportional to the lipophilicity of the drug, with the Vd
      of fluticasone being 332L compared with 183L for budesonide. Increasing the Vd
      will also increase the elimination half-life of a drug. The pharmacodynamics of
      ICS depend on both the receptor binding affinity and the dose-response curve.
      Among the ICS, fluticasone and mometasone have the highest receptor binding
      affinity (1800 and 2200, respectively), followed by budesonide at 935 (relative
      to dexamethasone = 100). Compared with other nonsteroid asthma medications (long
      acting beta-agonists, theophylline, and montelukast) ICS have proven superiority
      in improving lung function, symptom-free days, and inflammatory markers. One
      study suggests that early intervention with ICS reduces the loss in lung function
      (forced expiratory volume in 1 second) over 3 years. Whether airway remodeling is
      reduced or prevented in the long term is unknown. Potential adverse drug effects
      of ICS include adrenal and growth suppression. While in low-to-medium doses ICS
      have shown little suppression of the adrenal pituitary axis, in high doses the
      potential for significant adrenal suppression and adrenal crisis exists. Several
      longitudinal studies evaluating the effect of ICS on growth have shown a small
      decrement in growth velocity (approximate 1-2 cm) during the first year of
      treatment. However, when investigators followed children treated with budesonide
      for up to 10 years, no change in target adult height was noted. In conclusion,
      the development of optimal delivery devices for young children, as well as
      optimizing favorable pharmacokinetic properties of ICS should be priorities for
      future childhood asthma management.

PMID- 17523701
TI  - Aspirin and Reye syndrome.

PMID- 17523700
TI  - Aspirin and Reye syndrome: a review of the evidence.
AB  - Reye syndrome is an extremely rare but severe and often fatal disease. Death
      occurs in about 30-40% of cases from brainstem dysfunction. The disease typically
      is preceded by a viral infection with an intermediate disease-free interval of 3
      5 days. The biochemical explanation for Reye-like symptoms is a generalized
      disturbance in mitochondrial metabolism, eventually resulting in metabolic
      failure in the liver and other tissues. The etiology of 'classical' Reye syndrome
      is unknown. Hypothetically, the syndrome may result from an unusual response to
      the preceding viral infection, which is determined by host genetic factors but
      can be modified by a variety of exogenous agents. Thus, several infections and
      diseases might present clinically with Reye-like symptoms. Exogenous agents
      involve a number of toxins, drugs (including aspirin [acetylsalicylic acid]), and
      other chemicals. The 'rise and fall' in the incidence of Reye syndrome is still
      poorly understood and unexplained. With a few exceptions, there were probably no
      new Reye-like diseases reported during the last 10 years that could not be
      explained by an inherited disorder of metabolism or a misdiagnosis. This may
      reflect scientific progress in the better understanding of cellular and molecular
      dysfunctions as disease-determining factors. Alternatively, the immune response
      to and the virulence of a virus might have changed by alteration of its genetic
      code. The suggestion of a defined cause-effect relationship between aspirin
      intake and Reye syndrome in children is not supported by sufficient facts.
      Clearly, no drug treatment is without side effects. Thus, a balanced view of
      whether treatment with a certain drug is justified in terms of the benefit/risk
      ratio is always necessary. Aspirin is no exception.

PMID- 17523703
TI  - Efficacy and tolerability of moxifloxacin in patients with sinusitis treated in
      general practice : results of a post-marketing surveillance study.
AB  - OBJECTIVE: To assess the efficacy, safety and tolerability of moxifloxacin, an 8
      methoxy fluoroquinolone, in patients with respiratory tract infections (RTIs)
      treated in general practice in Germany. Different RTIs were analysed separately,
      and this paper focuses on patients with acute sinusitis. METHODS, DESIGN AND
      PATIENTS: This was an open-label, prospective, uncontrolled, post-marketing
      surveillance study undertaken between October 2001 and June 2002. Symptoms of
      sinusitis (fever, cough, nasal obstruction, nasal secretion and headache) were
      assessed at baseline and at follow-up visits, and classified as 'absent', 'mild'
      or 'severe' by the attending physician. RESULTS: Altogether 9036 patients were
      treated with moxifloxacin, of whom 2405 adult men and women had sinusitis.
      Sinusitis symptoms were improved or cured in at least 92% of patients.
      Moxifloxacin produced significant improvements after only 3 days (71.6% of
      patients); 96.2% of patients were improved after 5 days. Most patients (89.5%)
      had recovered by day 8 and 97.3% by day 10. Physicians rated moxifloxacin therapy
      as 'good' or 'very good' in 96.6% of patients and almost all favoured prescribing
      moxifloxacin in the future. Very few adverse events were reported with
      moxifloxacin (<0.4%), and were mostly gastrointestinal disturbances. CONCLUSIONS:
      Moxifloxacin is a very effective and safe treatment for patients with acute
      sinusitis in general practice and is highly regarded by both physicians and
      patients because of rapid symptom improvement and good tolerability.

PMID- 17523704
TI  - Once-daily moxifloxacin therapy for community-acquired pneumonia in general
      practice : evidence from a post-marketing surveillance study of 1467 patients.
AB  - OBJECTIVE: To assess the efficacy, safety and tolerability of oral moxifloxacin
      in outpatients with respiratory tract infections treated in general practices in
      Germany with the focus on community-acquired pneumonia (CAP). METHODS, DESIGN AND
      PATIENTS: This was an open-label, prospective, uncontrolled, post-marketing
      surveillance study undertaken between October 2001 and June 2002. Symptoms
      associated with pneumonia were documented at baseline and at follow-up visits. A
      general assessment was given and the number of days until improvement/cure were
      recorded by the attending physician at the end of therapy. RESULTS: A total of
      9036 patients were treated with moxifloxacin, of which 1467 had CAP. The
      recommended dosage of moxifloxacin (400mg once daily) was used in 97.8% of all
      CAP patients. Between the initial and final follow-up visits, symptoms of CAP
      were either improved or cured in 90-99% of patients. More than half of the
      patients showed improvement after 3 days (54.2%); 89.2% of patients were improved
      after 5 days. The mean time for patients to recover was 8.0 +/- 2.7 days, with
      88.7% of patients recovered by day 10 of treatment. Physicians rated moxifloxacin
      therapy as 'very good' or 'good' in 96.6% of patients and virtually all favoured
      prescribing moxifloxacin again. Ten patients (0.7%) reported adverse events
      during moxifloxacin therapy, mostly gastrointestinal disturbances. CONCLUSIONS:
      Moxifloxacin is a very effective and safe treatment for patients with CAP and is
      highly accepted by physicians and patients because of rapid symptom improvement
      and good tolerability.

PMID- 17523705
TI  - Daily-practice treatment of acute exacerbations of chronic bronchitis with
      moxifloxacin in a large cohort in Germany.
AB  - OBJECTIVE: To monitor the efficacy and safety of moxifloxacin in respiratory
      tract infections (RTIs) focussing on acute exacerbations of chronic bronchitis
      (AECB). METHODS: Patients with RTIs could be enrolled in this open-label,
      prospective, non-controlled post-marketing surveillance study from October 2001
      until June 2002 unless moxifloxacin was contraindicated. At the initial visit,
      data were recorded on patient demographics, diagnosis and clinical symptoms. Two
      follow-up examinations could be performed to determine cure or improvement based
      on clinical symptoms, and to record adverse events. Clinical symptoms including
      fever, cough and purulent sputum were assessed individually. Efficacy,
      tolerability and patient acceptance were assessed globally at the final visit.
      RESULTS: Of 9036 enrolled patients, 4328 had AECB, most of whom were treated with
      moxifloxacin at a daily dose of 400mg. Mean +/- SD time to clinical improvement
      was 3.4 +/- 1.5 days, and mean +/- SD time to clinical cure was 6.6 +/- 2.4 days.
      Cure rates were 39.4% at day 5 and 94.3% at day 10. By day 6, the proportion of
      patients with severe cough decreased from 85.4% at the initial visit to 6.9%, and
      those with severe dyspnoea from 22.5% to 1.2%. Purulent sputum was absent within
      4 days in the majority of cases. Physicians rated efficacy, tolerability and
      patient acceptance as 'very good' or 'good' in approximately 95% of patients.
      There were 59 adverse events in 44 (1.0%) patients, most frequently
      gastrointestinal and nervous system disorders. CONCLUSIONS: This study further
      confirms that AECB patients treated with moxifloxacin benefit from more rapid
      symptom relief and that this therapy option is well accepted in general practice.

PMID- 17523706
TI  - Incidence of adverse reactions to vaccines in a paediatric population.
AB  - OBJECTIVE: To detect the appearance and specify the types of adverse reactions to
      vaccines registered in a paediatric population. PATIENTS AND METHODS: A 6-month,
      prospective, observational, multicentre epidemiological vaccine safety study was
      undertaken in 2002 covering a paediatric population subject to vaccine
      administration. A two-phase telephone survey of all patients was conducted,
      comprising an initial call at 1 week and a follow-up call at 30 days after the
      vaccine administration date. A paediatrician was responsible for diagnosing the
      specific type of adverse reaction. RESULTS: Of a total sample of 946 children,
      ranging in age from 0 to 14 years (50.8% girls, 49.1% boys), 191 non-serious
      suspected adverse reactions were detected, representing 19% of the vaccinated
      children. Reactions to the diphtheria, tetanus, pertussis acellular and
      Haemophilus influenzae type b (DTPa + Hib) vaccine appeared in 43.4% of cases,
      followed by reactions to the measles, mumps, rubella (MMR) [18.4%] and adult
      tetanus and diphtheria (Td) [17.8%] vaccines. The most frequent types of adverse
      reactions to vaccines were: injection-site oedema (12.2 per 1000 doses); pain at
      site of inoculation (10.3 per 1000 doses); temperature not recorded but believed
      by parents to be very high (4.6 per 1000 doses); and measured temperature
      indicating fever of 39-40.5 masculineC (4.4 per 1000 doses). Fifty-five percent
      (n = 21) of cases of injection-site oedema were attributed to DTPa + Hib vaccine
      (18.8 per 1000 doses), followed by 18.4% (n = 7) attributable to Td vaccine (112
      per 1000 doses). Indeed, this latter vaccine was responsible for 43.8% (n = 14;
      226 per 1000 doses) of all reported pain at the site of inoculation. MMR vaccine
      was linked to the occurrence of fever of 39-40.5 masculineC in 52% of cases (n =
      10; 29 per 1000 doses). Two children were treated by the emergency services, but
      there were no deaths or hospitalisations. CONCLUSIONS: An active search for
      subjects with suspected adverse reactions to vaccines led to the detection of
      reactions that are usually not reported. Primary-care physicians and nurses must
      be vigilant for information on adverse reactions to vaccines in paediatric
      populations.

PMID- 17523707
TI  - Efficacy, safety and tolerability of combined low-dose simvastatin-fenofibrate
      treatment in primary mixed hyperlipidaemia.
AB  - OBJECTIVE: In order to assess the long-term (12 months) efficacy and safety of
      fenofibrate administered with simvastatin in the treatment of primary mixed
      hyperlipidaemia, we conducted a study that compared increasing dosages of these
      drugs in subgroups of men and women belonging to a clinical sample of out
      patients. DESIGN: This was an open study carried out in patients with primary
      mixed hyperlipidaemia (lipoprotein phenotype IIb) who needed a combined
      therapeutic approach because of their poor response to a single-drug regimen with
      an HMG-CoA reductase inhibitor (simvastatin). Thus, a fibrate (fenofibrate) was
      added to the therapy. The study lasted 12 months. PATIENTS: Forty-five patients
      (mean age: 58.9 +/- 11.3 years) with primary mixed hyperlipidaemia who showed a
      poor response to the single-drug hypolipidaemic treatment were enrolled. Their
      average plasma triglyceride level was consistently above 300 mg/dL and low
      density lipoprotein cholesterol (LDL-C) was over 160 mg/dL after at least 6
      months of a single hypolipidaemic drug (simvastatin) regimen plus antiatherogenic
      dietary treatment. INTERVENTIONS: Five patients received simvastatin 10mg once
      daily in addition to fenofibrate 200mg; 26 patients received simvastatin 20mg
      once daily plus fenofibrate 200mg; 11 patients received simvastatin 20mg once
      daily plus fenofibrate 300mg; and three patients received simvastatin 30mg once
      daily plus fenofibrate 200mg. The patients were allocated to treatment groups on
      the basis of their relative response to the therapy. Those making up the
      progressively higher agent/dose groups were the individuals at higher
      cardiovascular risk according to the total cholesterol and non-high-density
      lipoprotein cholesterol (HDL-C) values. RESULTS: The double-drug regimen given
      for 12 months to four different groups, according to the different combined
      dosages of simvastatin and fenofibrate, resulted in a reduction in total
      cholesterol of 18% (p </= 0.05) to 39% (p </= 0.05), in LDL-C of 21% (not
      significant) to 39% (p </= 0.05) and in triglycerides of 35% (p </= 0.05) to 56%
      (p </= 0.01), and an increase in HDL-C of 8% (p </= 0.05) to 30% (not
      significant). The cardiovascular risk ratio (total cholesterol/HDL-C) at the end
      of the study was reduced by 33-60%, whereas the non-HDL-C decreased by 25-38%. No
      serious adverse effects were reported by the patients. Neither liver biochemistry
      nor creatine kinase serum concentration were significantly changed.
      Discontinuation of treatment, if necessary, in case of the occurrence of
      clinically subjective or objective evidence of adverse effects was assured.
      CONCLUSION: The results confirmed the efficacy of the combination of fenofibrate
      and simvastatin. The combined therapeutic approach was shown to be safe for the
      treatment of primary mixed hyperlipidaemia, at least in patients with normal
      hepatic and renal function.

PMID- 17523708
TI  - Therapeutic drug monitoring in patients with inflammatory bowel disease and
      established azathioprine therapy.
AB  - BACKGROUND AND OBJECTIVE: Azathioprine is widely used in the treatment of
      corticosteroid-dependent and refractory inflammatory bowel disease (IBD). The
      efficacy of this treatment is based on the production of 6-thioguanine
      nucleotides, but extremely elevated levels may cause bone marrow suppression.
      Other azathioprine metabolites, 6-methylmercaptopurine ribonucleotides, are
      associated with hepatotoxicity. Therapeutic drug monitoring (TDM) may be of help
      in optimising azathioprine treatment, but data on TDM in established azathioprine
      therapy are lacking. We therefore measured metabolite levels in a small cohort of
      patients established on azathioprine therapy. PATIENTS AND METHODS: 6-Thioguanine
      (6-TGN) and 6-methylmercaptopurine (6-MMP) levels in erythrocytes were measured
      in 15 IBD outpatients established on azathioprine therapy for at least 3 months
      at baseline and 1, 4 and 8 weeks after inclusion (mean duration of treatment 28
      months; range 7-67 months). Disease activity was evaluated by the Crohn's Disease
      Activity Index (Crohn's disease) or Truelove-Witts (ulcerative colitis) scores.
      Metabolite levels were measured by modified high-performance liquid
      chromatography assay (HPLC). Primary outcome measures were 6-TGN and 6-MMP
      metabolite levels and 95% confidence intervals (CIs). SECONDARY OUTCOMES were
      correlations between metabolite levels, drug dose, disease activity and
      laboratory parameters and compliance. RESULTS: One patient had active disease
      during the study period. Eleven of 15 patients (73%) completed the 8-week study
      period. Dropout reasons were noncompliance in three patients (20%) and
      intolerance in one patient (7%). PRIMARY OUTCOMES: At baseline mean 6-TGN levels
      were 158 (95% CI 113, 203) pmol/8.10(8) RBC (red blood cells), steadily
      increasing over the 8-week study period, but not significantly. Two patients had
      zero levels. Another two had significantly increasing levels also suggesting
      noncompliance. Mean 6-MMP levels showed almost a similar pattern. At baseline,
      levels were 2213 (95% CI 722, 3704) pmol/8.10(8) RBC. SECONDARY OUTCOMES: A
      correlation was found between all RBC 6-MMP levels and azathioprine dose (mg/kg
      bodyweight) [r = 0.43, p = 0.001] and also between the 6-MMP/6-TGN ratio and
      azathioprine dose (mg/kg) [r = 0.36, p = 0.010). There was no correlation between
      RBC 6-TGN or 6-MMP levels and haematological parameters or disease activity
      scores. No hepatic, pancreatic or myelotoxicity occurred.Thirteen of 15 patients
      (87%) had baseline steady-state 6-TGN levels below the therapeutic threshold of
      235 pmol/8.10(8) RBC. Forty percent (6/15) of our patients were noncompliant; TDM
      revealed this noncompliance in four of the six patients (27% of all patients).
      CONCLUSION: Our small study demonstrates that TDM may provide insight into
      individual pharmacokinetics. However, TDM does not seem to be useful in patients
      with IBD established on azathioprine therapy and without disease activity,
      although it may be helpful in cases of worsening IBD activity to elucidate
      noncompliance or inefficient treatment.

PMID- 17523709
TI  - Levofloxacin-induced taste perversion, blurred vision and dyspnoea in a young
      woman.

PMID- 17523710
TI  - Acute Pulmonary Oedema Induced by COX-2 Inhibitors in a Patient with Chronic
      Pain.

PMID- 17523711
TI  - Pityriasis Rosea-Like Eruption due to Lithium.

PMID- 17523712
TI  - Divalproex to divalproex extended release conversion.
AB  - OBJECTIVE: Divalproex extended release (ER) tablets have lower bioavailability
      than conventional divalproex tablets. Objectives were to provide dose-increment
      justification for conversion of a patient from conventional enteric-coated
      divalproex to a once-daily divalproex ER regimen and to discuss the
      pharmacokinetic factors affecting these unequal total daily dose conversions.
      METHODS: Three bioavailability studies (two in healthy volunteers and one in
      epilepsy patients; total n = 69) compared equal total daily doses, and two
      studies (one each in healthy volunteers and epilepsy patients; total n = 99)
      compared 8-20% higher divalproex ER daily doses with corresponding divalproex
      total daily doses. In all five studies, multiple doses were administered over 6
      14 days in each regimen. RESULTS: For equal total daily dose comparisons, the
      divalproex ER/divalproex bioavailability (area under the concentration-time curve
      [AUC] ratio) was ~0.89 and when the divalproex ER dose was higher, the two
      regimens were equivalent (AUC ratio ~1.0). Divalproex ER administered once daily
      had less fluctuation in valproic acid concentrations, i.e. divalproex ER achieved
      equal or significantly higher minimum concentrations and significantly lower
      maximum concentrations compared with divalproex administered multiple times
      daily. Divalproex ER predose trough concentration consistently represented the
      lowest concentration during a dosing interval, whereas for divalproex this was
      not true because of absorption lag time (from enteric coating), diurnal variation
      and multiple doses during a 24-hour interval. CONCLUSIONS: An 8-20% higher
      divalproex ER daily dose should be used when converting from a total daily dose
      of divalproex. The lower fluctuation of valproic acid concentrations, consistent
      time to trough concentration, and lower dosing frequency of divalproex ER should
      offer benefit to the patient by providing convenient once-daily administration,
      and to the clinician by facilitating easier and reliable therapeutic drug
      monitoring and improving patient adherence.

PMID- 17523713
TI  - What Is the Best Strategy for Converting from Twice-Daily Divalproex to a Once
      Daily Divalproex ER Regimen? : Examinations and Answers via Computer Simulations.
AB  - OBJECTIVE: To examine if, during conversion from conventional divalproex to once
      daily divalproex extended-release (ER) tablets, plasma valproic acid (VPA)
      concentrations in the first 48 hours after conversion are maintained within the
      accepted therapeutic range (50-100 mg/L). METHODS: Four distinct 12-hourly (q12h)
      divalproex to once-daily divalproex ER conversion strategies were explored:
      immediate, delayed, stepwise and mixed conversion. These strategies were each
      used in simulations for hypothetical adult patients being treated under different
      conditions: monotherapy (uninduced, at 1500 mg/day divalproex ER) and polytherapy
      on enzyme-inducing co-medications (induced, at 3000 and 4500 mg/day divalproex
      ER). RESULTS: The proportion of uninduced patients expected to have minimum VPA
      concentrations (C(min)) >50 mg/L was 90% for immediate, 83% for stepwise and 82%
      for mixed-conversion strategies; only 52% undergoing a delayed-conversion
      strategy had C(min) >50 mg/L. More importantly, 33% of induced patients under
      going delayed conversion to 3000 mg/day divalproex ER maintained an adequate VPA
      C(min). Maximum VPA concentrations (C(max)) attained after conversion to
      divalproex ER are unlikely to rise beyond the steady-state C(max) observed with
      divalproex q12h regimens with any conversion strategy tested in uninduced or
      induced patients. Marked perturbation in VPA concentration is not likely when
      converting to once-daily divalproex ER 'all-at-once' 12 hours after the last
      divalproex q12h dose. Stepwise and mixed-conversion strategies do not offer any
      advantage; delayed conversion may produce a large drop in VPA concentration.
      CONCLUSIONS: An ideal conversion strategy for q12h divalproex to once-daily
      divalproex ER appears to be an immediate conversion 12 hours after the last
      divalproex q12h dose; it causes the least perturbation in plasma VPA, even for
      patients required to take high divalproex ER doses.

PMID- 17523714
TI  - Prophylactic effectiveness of tobramycin-dexamethasone eye drops compared with
      tobramycin/vehicle eye drops in controlling post-surgical inflammation in
      cataract patients : prospective, randomised, double-masked, two-arm, parallel
      group, placebo-controlled, multicentre study.
AB  - OBJECTIVE: To demonstrate the superiority of TobraDex((R)) (tobramycin 3 mg/mL,
      dexamethasone 1 mg/mL) eye drops over Tobrex((R)) (tobramycin 3 mg/mL)/vehicle
      (placebo) eye drops in the prophylaxis of inflammation after cataract surgery,
      and to provide additional safety data on TobraDex((R)). SETTING: Twenty-two
      ophthalmology clinics from Brazil, Belgium, Germany, Ireland, Portugal, Spain and
      Sweden. PATIENTS AND METHODS: Prospective, randomised, double-masked, two-arm,
      parallel-group, placebo-controlled, multicentre study in 417 patients undergoing
      extracapsular cataract extraction with intraocular lens implantation. Patients
      were randomised (1 : 1) to TobraDex((R)) or to Tobrex((R))/vehicle. One drop of
      TobraDex((R)) or Tobrex((R)) was instilled in the operative eye (four times
      daily) on the day before surgery (day -1), one drop immediately following surgery
      in the operated eye (day 0), and then treatment (four times daily) was continued
      until day 7 (inclusive). From day 8 through day 21, patients in the TobraDex((R))
      group continued with the same treatment, but patients in the Tobrex((R))/vehicle
      arm received the inactive ingredient only. Efficacy was assessed at 1, 3, 8, 14
      and 21 days. The primary efficacy variable was the percentage of patients without
      post-surgical anterior chamber inflammation (i.e. with a sum of cells and flare
      scores of zero) on the day 8 visit. RESULTS: TobraDex((R)) was significantly
      better (p < 0.05) than Tobrex((R))/vehicle in controlling post-surgical
      inflammation at day 8 as shown by the percentage of patients with an inflammation
      score of zero (51% vs 21%, respectively). The percentage of patients with
      treatment failure was 4% vs 16% (p < 0.001) in favour of TobraDex((R)). In the
      safety population (n = 415), 19% of patients reported a total of 52 adverse
      events while receiving TobraDex((R)) and 35.3% patients reported 103 adverse
      events while receiving Tobrex((R))/vehicle. One patient receiving
      Tobrex((R))/vehicle discontinued the study due to an ocular allergic reaction. No
      patient experienced clinically relevant changes in visual acuity, fundus
      parameters, cup/disc ratio or intraocular pressure related to treatment following
      the day of surgery. CONCLUSIONS: TobraDex((R)) eye drops were superior to
      Tobrex((R))/vehicle in controlling post-surgical inflammation following cataract
      extraction. TobraDex((R)) administered four times daily over 21 days post-surgery
      was safe and well tolerated in patients treated for the prevention of post
      surgical inflammation following cataract extraction.

PMID- 17523715
TI  - Sodium and potassium disturbances in the elderly : prevalence and association
      with drug use.
AB  - OBJECTIVE: To study the incidence of sodium and potassium disturbances in a
      population of the very old elderly, with respect to medication with potential
      effects on electrolyte levels. DESIGN AND SETTING: Cross-sectional study of
      subjects aged >/=75 years, based on data from the Kungsholmen project, a
      population-based study of elderly in an urban area of Stockholm, Sweden. STUDY
      PARTICIPANTS: 1558 elderly individuals (1178 women and 380 men), mean age 81.4
      years, providing information about drug use and serum electrolyte data. MAIN
      OUTCOME MEASURES: Data on drug use was based on personal interviews.
      Hyponatraemia was defined as a serum sodium concentration <136 mmol/L,
      hypernatraemia as a serum sodium concentration >146 mmol/L, hypokalaemia as a
      serum potassium concentration <3.5 mmol/L and hyperkalaemia as a serum potassium
      concentration >5.0 mmol/L. RESULTS: Hyponatraemia was found in 147 subjects (9.4%
      of the study population) and hypernatraemia in five individuals (0.3%).
      Hypokalaemia was found in 39 (2.5%) and hyperkalaemia in 43 (2.8%) of the
      subjects. The prevalence of hyponatraemia (p < 0.001), hypokalaemia (p < 0.05)
      and hyperkalaemia (p < 0.05) increased with age. Hyponatraemia was found more
      often in women than in men (p < 0.05). Hypernatraemia was more frequent in
      subjects who lived in institutions (p < 0.001). The occurrence of hyponatraemia
      was associated with the use of carbamazepine, laxatives (enema), diuretics and
      ACE-inhibitors; hypernatraemia was associated with osmotically active laxatives.
      Hypokalaemia was associated with thiazide-related and combination diuretics; and
      hyperkalaemia was associated with potassium-sparing diuretics, beta-blockers,
      cytostatic drugs and tricyclic antidepressants. CONCLUSIONS: The present study
      demonstrated the association between electrolyte level disturbances and several
      types of drugs in a population of the very old elderly. Our results underline the
      importance of monitoring serum electrolyte levels in the elderly, not only in
      relation to the use of diuretics, but also several other drugs.

PMID- 17523716
TI  - Efficacy and Safety Assessment of a Novel Once-Daily Tablet Formulation of
      Tramadol : A Randomised, Controlled Study versus Twice-Daily Tramadol in Patients
      with Osteoarthritis of the Knee.
AB  - OBJECTIVE: To compare the 24-hour sustained efficacy and safety of a new tramadol
      once-daily formulation (tramadol OAD) using Contramid((R)) controlled-release
      technology with a marketed twice-daily formulation (tramadol BID). PATIENTS,
      DESIGN AND SETTING: 431 patients with osteoarthritis of the knee were enrolled in
      this randomised, double-blind, multicentre, parallel study. After titration to
      optimum dose (range 100-400mg), patients received medication for 12 weeks. MAIN
      OUTCOME MEASURES AND RESULTS: Efficacy evaluations included: Western Ontario and
      McMaster University Osteoarthritis Index (WOMAC) scores (pain, stiffness,
      physical function and global), daily efficacy ratings (post-dose: tramadol OAD 24
      hours; tramadol BID 12 hours), pain ratings over 24 hours, and patient and
      investigator overall ratings. Non-inferiority was demonstrated for the primary
      endpoint, mean percentage change in WOMAC pain score from baseline to week 12
      (tramadol OAD 58%; tramadol BID 59%) [95% CI -7.67, 3.82]. The median optimum
      dose received was 200mg (both treatments). In 73% of patients, pain was mild to
      absent at the end of the dosing interval for both treatments (tramadol OAD 24
      hours; tramadol BID 12 hours). Pain ratings over 24 hours were similar between
      groups, indicating 24-hour sustained efficacy for tramadol OAD. More tramadol BID
      patients reported dizziness/vertigo (37% vs 26%), vomiting (14% vs 8%) and
      headache (18% vs 13%) while tramadol OAD patients reported more somnolence (30%
      vs 21%). CONCLUSIONS: This study demonstrated that this novel tramadol OAD
      formulation provides sustained analgesic efficacy over the entire 24-hour dosing
      interval and a clinically favourable safety profile, both of which will provide a
      clear clinical benefit.

PMID- 17523717
TI  - Acute Treatment of Facet Syndrome by CT-Guided Injection of Dexamethasone-21
      Palmitate Alone and in Combination with Mepivacaine.
AB  - OBJECTIVE: To compare the efficacy and tolerability of dexamethasone-21-palmitate
      and mepivacaine alone and in combination in the acute treatment of facet
      syndrome. PATIENTS AND METHODS: A total of 157 patients requiring acute therapy
      for lumbar facet syndrome were treated with computed tomography (CT)-guided intra
      articular infiltration of either an anti-inflammatory corticosteroid, a local
      anaesthetic or a combination of the two. Patients assigned to the first treatment
      group (n = 60) received the corticosteroid dexamethasone-21-palmitate
      (Lipotalon((R))); patients in the second group (n = 36) received the local
      anaesthetic mepivacaine (Meaverin((R))); patients in the third group (n = 61)
      received a combination of the two drugs. The study duration was from November
      2002 until June 2003. RESULTS: In all three groups, values for compression pain,
      stress pain and rest pain improved significantly from baseline within 1 hour of
      injection: in the dexamethasone monotherapy group there was a 13% reduction in
      compression pain, 20% reduction in stress, and 22% reduction in rest pain; in the
      groups that received mepivacaine only or a combination of the two drugs there was
      a 63% and 60%, respectively, reduction of compression pain, 81% and 83%,
      respectively, reduction of stress pain, and 84% and 77%, respectively, reduction
      of rest pain. After 72 hours, improvements in these variables were significantly
      greater in patients treated with dexamethasone-21-palmitate (either as
      monotherapy or in combination therapy) than in patients treated with mepivacaine
      alone. In both groups treated with dexamethasone palmitate there was a 57% and
      64%, respectively, reduction of compression pain, 70% and 66%, respectively,
      reduction of stress pain, and 75% and 64%, respectively, reduction of rest pain.
      In the mepivacaine monotherapy group there was a 17% reduction in compression
      pain, 26% reduction in stress pain and 13% reduction in rest pain. Both
      physicians and patients also rated the dexamethasone-21-palmitate-containing
      regimens as more effective than mepivacaine alone at 72 hours. Over the entire
      observation period, combination therapy was, on average, superior to both
      monotherapy regimens. The proportion of patients using concomitant NSAID
      medication after 3 days was reduced by 50% in the mepivacaine group and by 76%
      and 100%, respectively, in the dexamethasone-21-palmitate and combination therapy
      groups. CT-guided infiltration treatment was well tolerated and was associated
      with virtually no side effects in this study. CONCLUSION: CT-guided infiltration
      of dexamethasone palmitate, particularly in combination with mepivacaine,
      represents a safe and effective method for the acute therapy of lumbar facet
      syndrome. The combination is superior to the local anaesthetic alone with regard
      to pain reduction up to 3 days after injection.

PMID- 17523718
TI  - A Randomised, Controlled Comparison of Low-Dose Polyethylene Glycol 3350 plus
      Electrolytes with Ispaghula Husk in the Treatment of Adults with Chronic
      Functional Constipation.
AB  - OBJECTIVE: To compare the efficacy and safety of polyethylene glycol (PEG) 3350
      plus electrolytes (PEG+E; Movicol((R))) with that of ispaghula husk (psyllium;
      Konsyl((R))) in the treatment of constipation. PATIENTS: Male or female adults
      with chronic functional constipation. METHODS: This was a randomised, controlled,
      open-label, parallel-group trial. Study treatment was either PEG+E 13.8g/sachet
      dissolved in water twice daily or ispaghula husk 3.5g/sachet dissolved in water
      twice daily for a period of 2 weeks. Assessments were at baseline and after 1 and
      2 weeks' therapy and by patient daily diary card. The primary outcome measures
      were weekly defaecation rate, stool consistency according to the Bristol Stool
      Form scale, time to first defaecation, and overall efficacy, which combined
      defaecation rate, stool consistency and difficulty on defaecation. Adverse
      effects were recorded and laboratory assessments were performed before and at the
      end of the treatment period. RESULTS: Sixty-three patients were randomised to
      each treatment group. Treatment was highly effective in 50/63 patients in the
      PEG+E group compared with 26/63 in the ispaghula husk group, and the overall
      efficacy rates were 92% and 73%, respectively (p = 0.005). PEG+E increased the
      mean weekly defaecation rate from 1.18 (SD 0.77) at baseline to 7.95 (SD 3.49)
      after 1 week and 8.48 (SD 3.55) after 2 weeks. In the ispaghula husk group the
      mean weekly defaecation rate increased from 1.33 (SD 0.68) at baseline to 5.33
      (SD 2.81) after 1 week and to 5.71 (SD 2.49) after 2 weeks. The treatment
      differences for defaecation rates were all statistically significant (p < 0.001).
      Two weeks of treatment with PEG+E or ispaghula husk normalised stools in 55/63
      (87.3%) and 42/63 (66.7%) of patients (p < 0.001). The incidence of adverse
      effects did not differ between groups and none were serious or required any
      treatment. Laboratory evaluations found no adverse effect from either treatment.
      CONCLUSION: The present study demonstrated that low-dose PEG 3350 plus
      electrolytes is more effective and more rapid in its onset of action than
      ispaghula husk, and is equally well tolerated.

PMID- 17523719
TI  - Short-course, low-dose oral betamethasone as an adjunct in the treatment of acute
      infective sinusitis : a comparative study with placebo.
AB  - OBJECTIVE: To assess the effect of a short course of low-dose oral corticosteroid
      used as an adjunct to antimicrobials in patients with acute infective sinusitis.
      STUDY DESIGN AND PATIENTS: Double-blind, randomised, placebo-controlled study
      including 42 patients with a clinical diagnosis of acute infective sinusitis. The
      study was performed at three primary healthcare sites in South Africa during the
      period January-November 2003. INTERVENTION: Two equal groups received either
      betamethasone 1mg orally (n = 21; the treatment group) or placebo tablets (n =
      21; the placebo group) once a day in the morning for five consecutive days. All
      patients received amoxicillin-clavulanic acid 625mg orally, three times daily for
      5 days. MAIN OUTCOME MEASURE: Patients rated symptoms on a daily symptom score
      card for 5 days and were examined by the investigator at diagnosis (day 0) and on
      the second visit (day 6). RESULTS: Headache, facial pain, nasal congestion and
      dizziness improved significantly from baseline in the treatment group compared
      with the placebo group over 5 days of treatment (p = 0.028, p </= 0.047, p </=
      0.04 and p </= 0.051, respectively). Percussion tenderness improved significantly
      (p = 0.049) and clearance of purulent secretions almost reached significance (p =
      0.058) in the treatment group compared with the placebo group. CONCLUSION: This
      study suggests a benefit of oral corticosteroid added to antimicrobial treatment
      of acute sinusitis and documents the first successful use of a short course of
      low-dose oral corticosteroid in patients with acute infective sinusitis.

PMID- 17523720
TI  - Salmeterol/Fluticasone Propionate in a Single Inhaler is Superior to Budesonide
      Alone in Control of Chinese Asthmatic Adults : An Open-Label, Randomised, 6-Week
      Study.
AB  - OBJECTIVE AND DESIGN: There is comparatively little information on asthma
      management in China. A multicentre, randomised, open-label, parallel-group, 6
      week treatment study was conducted to evaluate the efficacy and safety of
      salmeterol/fluticasone propionate combination treatment in Chinese adult
      asthmatic patients. SETTING AND PATIENTS: 398 patients with a documented history
      of moderate-to-severe asthma were randomised to treatment. INTERVENTIONS:
      Salmeterol 50mug/fluticasone propionate 100mug twice daily for 6 weeks via
      Accuhaler((R)) (Diskustrade mark) inhaler and budesonide 400mug twice daily for 6
      weeks via Turbuhaler((R)) inhaler. MAIN OUTCOME MEASURES AND RESULTS: Morning
      peak expiratory flow (PEF) was investigated as the primary efficacy endpoint;
      evening PEF, use of salbutamol (albuterol) as rescue medication, and day- and
      night-time asthma symptom scores were secondary efficacy endpoints. Safety was
      assessed according to adverse events recorded. Over the 6-week treatment period,
      salmeterol/fluticasone propionate led to a significantly greater increase in
      morning (p < 0.0001) and evening (p = 0.0066) PEF compared with budesonide.
      Moreover, the significant benefit of salmeterol/fluticasone propionate was
      evident from the first week. Similarly, salmeterol/fluticasone propionate led to
      significantly greater improvements in the use of rescue medication and day- and
      night-time asthma symptom scores, compared with budesonide. Both treatments were
      well tolerated, with a similar incidence (23%) of adverse events in both
      treatment groups and no serious adverse events. CONCLUSIONS:
      Salmeterol/fluticasone propionate 50mug /100mug twice daily was significantly
      more effective than budesonide 400mug twice daily in improving lung function and
      reducing symptoms and use of rescue medication in Chinese asthmatic patients who
      were poorly controlled on low-dose inhaled corticosteroids. This confirms the
      findings of superior efficacy of this combination product over budesonide in
      other populations.

PMID- 17523721
TI  - Efficacy and Safety of Valsartan 160mg/Hydrochlorothiazide 25mg Combination in
      Patients with Hypertension not Adequately Controlled by Valsartan
      160mg/Hydrochlorothiazide 12.5mg.
AB  - BACKGROUND AND OBJECTIVE: Hypertension guidelines emphasise the need to treat
      high blood pressure (BP) early and aggressively, giving fixed-dose combinations
      special consideration. Hitherto, it has not been assessed in a sequential way
      whether hypertensive patients with inadequately controlled hypertension with an
      angiotensin II receptor antagonist/hydrochlorothiazide combination benefit from a
      dose increase of the diuretic. We investigated the efficacy and safety of
      valsartan 160mg/hydrochlorothiazide 25mg combination in patients with
      hypertension that was not adequately controlled by valsartan
      160mg/hydrochlorothiazide 12.5mg. PATIENTS AND METHODS: This was a multicentre,
      single-group, prospective study of 646 patients with moderate hypertension
      (diastolic BP [DBP] 100-109mm Hg). Patients were treated for 4 weeks with
      valsartan 160mg/hydrochlorothiazide 12.5mg (phase 1: weeks 1-4). In case of non
      response (DBP >/=90mm Hg; n = 224) patients were treated for a further 4 weeks
      with valsartan 160mg/hydrochlorothiazide 25mg (phase 2: weeks 5-8). The primary
      efficacy measure was a change in mean sitting trough DBP at study end compared
      with the beginning of phase 2 in the intention-to-treat (ITT) population (n =
      221). RESULTS: Mean age of patients at entry was 58.6 years; 53.7% of patients
      were female. In phase 1, systolic BP (SBP)/DBP decreased from a baseline value of
      161.9/103.3mm Hg by -16.1/-12.4mm Hg (normalisation rate 38.3%, response rate
      64.5%). In phase 2, in the ITT non-responder population the additional SBP/DBP
      decrease was -8.4/-8.3mm Hg. Overall, the normalisation rate in all patients was
      55.4% and the responder rate was 76.3%.Tolerability of both the valsartan
      160mg/hydrochlorothiazide 12.5mg and the valsartan 160mg/hydrochlorothiazide 25mg
      combinations was very good, and the switch to the higher dose did not result in
      an increase in adverse events (AEs) or laboratory abnormalities. Only 16.6% of
      patients in phase 1 and 10.3% of patients in phase 2 experienced one or more AEs.
      CONCLUSION: In patients with moderate hypertension, first-line therapy with the
      fixed-dose valsartan/hydrochlorothiazide combination leads to high normalisation
      and response rates. Patients with hypertension not controlled by valsartan 160mg/
      hydrochlorothiazide 12.5mg clearly benefit from dose titration to valsartan
      160mg/hydrochlorothiazide 25mg with a clinically relevant additional BP response
      and have excellent tolerability.

PMID- 17523722
TI  - Pharmacoeconomic assessment of clinical pharmacist interventions for patients
      with moderate to severe asthma in outpatient clinics : experience in taiwan.
AB  - OBJECTIVE: To assess the economic and humanistic outcomes of clinical pharmacist
      interventions for patients with asthma and to assess the effect on patients'
      quality of life. STUDY DESIGN: A prospective cohort study was conducted at a
      medical centre in southern Taiwan. PATIENTS AND METHODS: Seventy patients with
      moderate to severe asthma were enrolled in the study from July 2003 to December
      2003. Patients who were 17-53 years of age and were attending the outpatient
      clinic were referred to the pharmacist intervention programme. Patients were
      educated about their disease, pharmacotherapy, self-management and inhalation and
      peak flow meter techniques to use during the intervention period. A modified
      Asthma Quality-of-Life Questionnaire (AQLQ) was given to the patients at the
      first intervention (baseline) and 3 months later (intervention period) to assess
      quality of life. An asthma general knowledge questionnaire and an asthma diary
      chart were also used to assess patients' knowledge about asthma and the
      improvement in their symptoms. The cost effectiveness was evaluated based on the
      reduction in total costs/mean cost at each visit. RESULTS: Of the 70 asthmatic
      patients enrolled in the study; 55 completed the questionnaires at baseline and
      after the intervention period. Only 25 of 55 (45.5%) patients completed the
      asthma diary chart. After the pharmacist intervention period, the patients'
      quality of life, common knowledge about asthma, and peak expiratory flow rate
      (PEFR) were significantly improved as compared with baseline (p < 0.001). The
      frequency of use of beta(2)-agonists and corticosteroids were also reduced,
      although the reduction was not statistically significant. Total cost per patient
      at baseline was statistically different from that after the 3-month intervention
      period (New Taiwanese dollars [$NT] 2880 vs $NT1683, respectively; costings are
      costs during the study period). CONCLUSION: For patients with moderate to severe
      asthma, pharmacist intervention can be a cost-effective addition to the
      management of patients at an outpatient clinic by improving PEFR and patient
      quality of life, and saving medical resources.

PMID- 17523723
TI  - Carboplatin in Combination with Bendamustine in Previously Untreated Patients
      with Extensive-Stage Small Cell Lung Cancer (SCLC).
AB  - BACKGROUND AND OBJECTIVE: Bendamustine is an alkylating agent with high efficacy
      in non-Hodgkin's lymphoma and multiple myeloma. Even in solid tumours,
      monotherapy with bendamustine has resulted in subjective remissions and has been
      associated with a low rate of side effects. The current dose-finding study was
      designed to determine the maximum tolerated dose (MTD) of combined
      carboplatin/bendamustine in previously untreated patients with extensive-stage
      small cell lung cancer (SCLC). PATIENTS AND METHODS: Carboplatin was administered
      as a 1-hour infusion on day 1 at increasing dose levels, and bendamustine was
      administered as a short infusion on days 1 and 2 at increasing dose levels (80
      120 mg/m(2)). The regimen was administered every 3 weeks. Four dose levels were
      planned, starting with 80 mg/m(2) bendamustine and carboplatin area under the
      curve (AUC) 5 (dose level I). The other dose levels were 100 mg/m(2) bendamustine
      and carboplatin AUC 5 (dose level II), 100 mg/m(2) bendamustine and carboplatin
      AUC 6 (dose level III), and 120 mg/m(2) bendamustine and carboplatin AUC 6 (dose
      level IV). A minimum of three patients were enrolled at each dose level. RESULTS:
      Dose-limiting toxicities, which included fatigue, infection and tachyarrhythmia,
      were observed at dose level III. The recommended dose for phase II studies was
      therefore established at dose level II. The majority of haematological and non
      haematological toxicities observed were only mild (grade 1 or 2) in patients at
      dose levels I and II. None of the patients developed severe alopecia. Objective
      responses were observed in eight of the ten patients involved in this trial.
      CONCLUSION: Because of its acceptable toxicity and favourable preliminary
      antitumour efficacy, the combination of carboplatin and bendamustine appears to
      be a potentially useful chemotherapeutic option in patients with extensive SCLC.

PMID- 17523724
TI  - Pharmacokinetics of Losartan and its Active Metabolite EXP3174 in Healthy Iranian
      Subjects.

PMID- 17523725
TI  - 'As-needed' prescription of zolpidem for insomnia in routine general practice.
AB  - OBJECTIVE AND DESIGN: This open, non-comparative, multicentre study was designed
      to evaluate zolpidem consumption and evolution of its use for the treatment of
      insomnia on an 'as-needed' basis, under the real conditions of routine general
      practice. PATIENTS AND METHODS: 1938 patients (aged >18 years) with insomnia
      (mean +/- SD duration: 3.0 +/- 15.2 months; median duration: 1 month) were
      enrolled. A maximum of 21 doses were prescribed for the treatment period (3 weeks
      maximum) and patients were instructed to take zolpidem according to their sleep
      disturbance ('as needed'). The main criteria were number of doses/week and
      consumption evolution over the treatment period. Secondary criteria included the
      evolution of disease severity, the evolution of parameters of sleep quality and
      factors predictive of the evolution of zolpidem consumption. RESULTS: Consumption
      decreased steadily during the study, from 5.1 +/- 1.9 doses/week during week 1 to
      3.7 +/- 2.5 doses/week during week 3. A prior sleep-disorder episode (p = 0.02),
      high initial zolpidem consumption with 6-7 doses/week (p < 0.001) or insomnia
      having started >3 weeks before the inclusion (p < 0.001) were predictive of
      stable or increased zolpidem consumption. Global clinical improvement showed
      moderate to very marked improvement for 90% of the patients. Other sleep-quality
      and clinical-improvement parameters indicated overall satisfaction. Nature,
      incidence and severity of safety data reported during the study were consistent
      with the safety experience reported to date. CONCLUSION: During zolpidem 'as
      needed' administration in general practice, patients adapted the treatment to
      their needs and to the evolution of their insomnia. The treatment had a good
      safety profile and was effective.

PMID- 17523726
TI  - Bioavailability and pharmacokinetics of intranasal hydromorphone in patients
      experiencing vasomotor rhinitis.
AB  - BACKGROUND AND OBJECTIVE: Narcotic analgesics such as hydromorphone undergo an
      extensive first-pass effect resulting in a low systemic bioavailability following
      oral administration. Alternative dosing routes, such as rectal and intranasal
      (IN) routes, have been suggested as options for oral or intravenous
      administration. Rhinitis and pharmacological agents used for treatment are
      considered factors that could alter the rate and extent of absorption of drugs
      administered by the nasal route. The purpose of this study was to evaluate the
      pharmacokinetics of intranasal hydromorphone hydrochloride (HCl) in patients with
      vasomotor rhinitis. METHODS: Ten patients completed the randomised, three-way
      crossover study. During the three treatment periods, a single dose of
      hydromorphone HCl 2.0mg was administered via intravenous infusion (treatment A)
      and the intranasal route without (treatment B) or with (treatment C)
      vasoconstrictor pretreatment for rhinitis. Blood samples were collected serially
      from 0 to 16 hours. Noncompartmental methods were used to determine
      pharmacokinetic parameters. RESULTS: Maximum plasma concentrations were 3.69 and
      3.38 mug/L for treatments B and C, respectively. Mean (% coefficient of
      variation) bioavailability of intranasal hydromorphone was 54.4% (34.8) and 59.8%
      (22.1) with and without pretreatment, respectively. Pretreatment of rhinitis did
      not significantly affect the rate or extent of absorption of hydromorphone in
      this study. There was not a significant difference in bioavailability between
      treated and untreated rhinitis. CONCLUSIONS: This study found intranasal
      administration of hydromorphone in patients experiencing vasomotor rhinitis had
      acceptable bioavailability and a pharmacokinetic profile comparable to previous
      studies. These data support further investigation of this single-dose delivery
      system for clinical use.

PMID- 17523727
TI  - Quality of care and attributable healthcare costs in diabetic hypertensive
      patients initiated on calcium antagonist therapy.
AB  - BACKGROUND AND OBJECTIVE: Calcium antagonists (CAs) from two classes -
      dihydropyridine and non-dihydropyridine (DCAs and NDCAs, respectively) - are
      important add-on agents in goal blood pressure (BP) attainment. This study
      compared drug regimens to which DCAs or NDCAs had been added; for each class, BP
      reduction and healthcare costs were evaluated in a diabetic hypertensive
      population. DESIGN, SETTING AND PATIENTS: This was a retrospective observational
      study using administrative claims data within two US health plans. Patients with
      diabetes mellitus (DM) and hypertension initiated on CA therapy between 1 January
      2000 through 30 June 2002 were identified; the date the first CA prescription (CA
      Rx) was filled in this period was labelled the index date. Inclusion required
      plan enrolment for 6 months pre- and 1 year post-index, no CA-Rx 6 months pre
      index, and medication possession ratio >50% for 1 year post-index. Patients fell
      into either dihydropyridine or non-dihydropyridine study groups. MAIN OUTCOME
      MEASURES AND RESULTS: For each group, costs (amounts allowed by plans, in US
      dollars; actual costs for 2000-2002) were calculated for resources attributable
      to DM/hypertension. A total of 5551 patients met eligibility criteria (NDCA =
      1515; DCA = 4036). Most had been taking other antihypertensive medications: 86%
      and 76% in the DCA and NDCA groups, respectively. The NDCA group had lower annual
      attributable costs than the DCA group ($US1637 [95% CI $US1479, $US1813] vs
      $US1989 [95% CI $US1823, $US2170]; p < 0.004). A total of 313 medical charts were
      reviewed (DCA = 242, NDCA = 71). Both groups had similar pre-and post-index BP
      values; mean changes in systolic and diastolic BP were not statistically
      significant between groups. Only 22% of all patients attained the recommended
      systolic/diastolic BP goal of <130/80mm Hg, and <45% of patients were tested for
      proteinuria during the study period. CONCLUSIONS: Patients initiated on an NDCA
      attained similar BP reductions compared with DCA at lower total healthcare costs.
      Opportunities exist for more aggressive management of BP and testing for
      proteinuria in DM patients with hypertension.

PMID- 17523728
TI  - Heart Rate Variability and Baroreflex Sensitivity during Fosinopril, Irbesartan
      and Atenolol Therapy in Hypertension.
AB  - OBJECTIVE: To evaluate the effects of long-term therapy with fosinopril,
      irbesartan and atenolol on the autonomic control of the cardiovascular system in
      hypertensive patients. METHODS: We enrolled 58 patients (mean age 38 +/- 10
      years) with never-treated mild hypertension with no evidence of target organ
      damage. The study was single blind. Patients were assigned to receive fosinopril
      10-20 mg/day, irbesartan 150-300 mg/day or atenolol 50-100 mg/day for 14 weeks.
      Dosage was titrated to reach an average office blood pressure (BP) of <140/90mm
      Hg. Before therapy all patients underwent a 24-hour Holter ECG to evaluate heart
      rate variability (HRV) through nonlinear methods, 24-hour ambulatory BP
      monitoring (ABPM), and measurement of baroreflex sensitivity (BRS) using a
      Portapres device; all measurements were repeated after therapy. RESULTS: All
      three therapies significantly and equally decreased BP, both office
      (systolic/diastolic blood pressure 152 +/- 11/97 +/- 7mm Hg vs 129 +/- 7/85 +/-
      4mm Hg after fosinopril, 151 +/- 11/97 +/- 6mm Hg vs 133 +/- 9/87 +/- 8mm Hg
      after irbesartan, 149 +/- 13/96 +/- 9mm Hg vs 132 +/- 9/87 +/- 7mm Hg after
      atenolol; p < 0.001) and ABPM values. HRV calculated with nonlinear methods and
      BRS were significantly increased after atenolol whereas no significant change was
      found in the fosinopril and irbesartan treatment groups. CONCLUSIONS: All three
      therapies significantly and similarly reduced BP without modifying heart rate,
      except for atenolol, which significantly decreased it. Although angiotensin
      directly increases sympathetic tone, neither fosinopril nor irbesartan modified
      cardiovascular autonomic function; this is likely to be connected to the fairly
      good basal autonomic function of the population evaluated. Atenolol is associated
      with a significant increase in HRV and BRS probably through an improvement of
      parasympathetic tone.

PMID- 17523729
TI  - Weekly Gemcitabine plus Fluorouracil-Folinic Acid Given Weekly for Two Days in
      Patients with Advanced Pancreatic Cancer : A Phase II Study.
AB  - OBJECTIVE: To investigate the efficacy and toxicity of gemcitabine administration
      followed by the combination of fluorouracil (5-FU) modulated by folinic acid in
      patients with advanced, symptomatic pancreatic cancer. The main objective was to
      estimate tumour response and any improvement in patients' quality of life.
      PATIENTS: The study included 48 evaluable patients with metastatic disease with
      no prior chemotherapy. The study duration was 3 years. INTERVENTIONS: Gemcitabine
      1000 mg/m(2) intravenously was given on days 1 and 8 followed by fluorouracil 350
      mg/m(2) intravenously as a bolus biologically modulated by folinic acid 350
      mg/m(2) intravenously given on days 1, 2, 8 and 9 in order to develop the
      conditions for any potential drug synergism. The regimen was administered every 3
      weeks for 1 year or until disease progression. RESULTS: Objective partial
      responses were documented in ten (21%) patients (95% CI 10.5, 35). Twenty-two
      (46%) patients had stable disease while 16 (33%) patients had progressive
      disease. The median response duration was 8 months (range 4-20). The median time
      to progression was 6 months (range 2-24), while the median survival of the group
      was 7 months (range 3-36) and the probability of surviving beyond 12 months was
      20%. Of the 44 patients with tumour-related symptoms who were considered
      evaluable for clinical-benefit response, 28 (70%) patients had pain improvement,
      25 (52%) patients had improvement of their performance status, and nine (28%)
      patients experienced weight gain during treatment. Serum concentrations of cancer
      antigen (Ca-19-9) were decreased by more than 50% in 14 (37%) of the 38
      assessable patients. Chemotherapy was well tolerated, with mild myelotoxicity.
      Gastrointestinal toxicity was moderate with mild mucositis. CONCLUSION: The
      regimen of gemcitabine and fluorouracil administered in this study was well
      tolerated and showed a moderate antitumour activity and a significant palliative
      effect on tumour-related symptoms. Because fluorouracil is a low toxicity
      combination agent for gemcitabine, other forms of the two-drug combination
      warrant further investigation.

PMID- 17523730
TI  - Effects of a Novel Aldose Reductase Inhibitor, Fidarestat (SNK-860), on Vibration
      Perception Threshold and Subjective Symptoms in Patients with Diabetic
      Polyneuropathy : An Open-Label Pilot Study.
AB  - OBJECTIVE: To evaluate the effects of fidarestat (SNK-860) on vibration
      perception threshold, as measured by C64 quantitative tuning fork (64Hz)
      analysis, as well as its effects on subjective symptoms in patients with diabetic
      polyneuro-pathy. DESIGN AND SETTING: Open-label, prospective study conducted at
      12 hospitals in the central area of Honshu, Japan. INTERVENTIONS: Fidarestat was
      administered at a dosage of 1mg once daily after breakfast for 28 weeks. MAIN
      OUTCOME MEASURES: Vibration perception threshold of upper and lower extremities
      was determined using a C64 quantitative tuning fork, and measured at baseline and
      after 12 and 28 weeks of treatment. Subjective symptoms, including numbness,
      spontaneous pain and hypoaesthesia, were evaluated every 4 weeks. RESULTS:
      Subjective symptoms were evaluated in 22 patients, and vibration perception
      threshold data were available for 19 patients. Vibration perception threshold at
      baseline was negatively correlated with the severity of the following subjective
      symptoms: numbness in the upper limbs, and numbness, coldness and hot flushes,
      smarting pain causing difficulty walking and hypoaesthesia in the lower limbs.
      During treatment with fidarestat, vibration perception threshold increased
      significantly in the upper (p = 0.0017) and lower (p = 0.0001) limbs. The
      following symptoms were also significantly improved: severity of numbness in the
      lower limbs, heaviness in the foot, coldness and hot flushes in the lower limbs,
      smarting pain causing difficulty walking, sensation as if walking on sand,
      sensation as if walking on an uneven road, spontaneous pain in the lower limbs,
      and dizziness. Adverse events occurred in four patients. CONCLUSION:
      Administration of fidarestat after breakfast was effective in significantly
      alleviating some symptoms of diabetic polyneuropathy. The C64 quantitative tuning
      fork analysis is useful in the diagnosis of diabetic polyneuropathy, and as a
      measure of the severity of the neuropathological symptoms of this condition.

PMID- 17523731
TI  - Ambroxol Lozenge Bioavailability : Part II - Analysis of Additional Systemic
      AvailabilityPart I of this article was published in Clin Drug Invest 2003; 23
      (4): 273-80.
AB  - OBJECTIVE: To examine whether or not the early dissolution/absorption in the oral
      cavity of lozenge administration contributes to superior bioavailability of
      ambroxol compared with the commercially available tablet. METHODS: 24-hour plasma
      level pharmacokinetic profiles of 20 healthy volunteers receiving oral
      administration of identical single doses (30mg) of lozenges and a commercially
      available tablet with a 1-week washout period were collected. The data were
      analysed by a non-compartmental model with a statistical moment and mean transit
      time concept. The mean transit times obtained after lozenge and tablet
      administration were compared. RESULTS: The variance in absorption phase was
      significantly higher than that in the distribution/elimination phase in the
      pharmacokinetic profiles of the lozenge, suggesting additional absorption
      processes. The mean transit time of the tablet was significantly greater than
      that of the lozenge, by 7.69 hours with a 90% confidence interval (CI) of 3.11,
      12.27. Early drug dissolution/absorption in the oral cavity and gastrointestinal
      absorption was successfully modelled to the pharmacokinetic profiles after
      lozenge administration. The additional availability of the drug to systemic
      circulation was mainly due to complete dissolution in the oral cavity prior to
      absorption as well as to oral mucosal transport. Between the two processes,
      dissolution was proposed to be a limiting step, since oral mucosal absorption was
      at a very high rate. The estimated average dissolution rate constant (90% CI) in
      first-order fashion was 0.13h(-1) (0.08, 0.32). CONCLUSION: Absorption rates
      between lozenge and tablet could be differentiated with the aid of the mean
      transit time concept. However, estimation of oral mucosal absorption was not
      possible because the blood sampling intervals were not sufficiently frequent.

PMID- 17523733
TI  - [Not Available].

PMID- 17523732
TI  - High Fever induced by dexamethasone withdrawal.

PMID- 17523734
TI  - Insulin aspart : an evidence-based medicine review.
AB  - This paper provides a review and evaluation of the published evidence relating to
      the efficacy, safety and ease of administration of the rapid-acting insulin
      analogue insulin aspart in comparison with human insulin (HI) in diabetes
      mellitus in the following categories: (a) in adults, (b) in children, and (c) in
      continuous subcutaneous insulin infusion (CSII). A search for publications on
      insulin aspart was conducted for the following databases: Cochrane, BIOSIS,
      EMBASE-DP and MEDLINE. Publications were examined for relevance by two
      independent assessors and were graded using a system developed by the Oxford
      Centre for Evidence-Based Medicine. Overall, the evidence comparing insulin
      aspart with HI was of high quality, with all three categories graded as grade A
      evidence. Studies showed strong evidence for better glycaemic control, without an
      increased risk of hypoglycaemia, together with evidence supporting improved
      convenience and flexibility in administration of insulin aspart compared with
      regular HI in adult diabetic patients. Evidence from three trials in adults with
      type 1 diabetes showed a lower incidence of major nocturnal hypoglycaemia with
      insulin aspart versus regular HI. Published evidence also confirmed the more
      rapid action of insulin aspart versus HI, and a comparable efficacy and safety
      profile for both insulin types in type 1 paediatric patients. There was also
      strong evidence that insulin aspart is well tolerated and efficacious for
      CSII/pump use. Insulin aspart better mimics the physiological response to meals
      than regular HI, and may offer advantages in terms of glycaemic control and
      reduction of hypoglycaemia combined with flexibility and convenience of
      administration. Overall, there is a good body of evidence to support the
      efficacy, tolerability and ease of administration of insulin aspart in patients
      with type 1 and type 2 diabetes.

PMID- 17523735
TI  - Pharmacoeconomic Impact of Low-Dose Macrogol 3350 plus Electrolytes Compared with
      Lactulose in the Management of Chronic Idiopathic Constipation among Ambulant
      Patients in Belgium.
AB  - OBJECTIVE: To estimate the economic impact of using low-dose macrogol 3350 plus
      electrolytes (macrogol 3350; Movicol((R))) compared with lactulose in the
      treatment of chronic idiopathic constipation among ambulant patients in Belgium,
      from the perspectives of the Sick Fund and patients. The analysis considered
      separately the economic impact of (a) a specialist and (b) a general practitioner
      (GP) initiating treatment. DESIGN AND SETTING: This was a modelling study
      performed from the perspective of Belgium's Sick Fund and patients. METHODS:
      Estimates of healthcare resource utilisation in a previously reported UK model
      depicting the management of chronic idiopathic constipation with either macrogol
      3350 and lactulose over 3 months were replaced with Belgian estimates derived
      from a panel of 11 gastroenterologists and 11 GPs. The model was used to estimate
      the expected 3-monthly Sick Fund cost and direct cost to patients of using either
      laxative to manage chronic idiopathic constipation in Belgium. MAIN OUTCOME
      MEASURES AND RESULTS: According to our model, 53% and 24% of patients are
      expected to be successfully treated with macrogol 3350 and lactulose,
      respectively. Additionally, using macrogol 3350 instead of lactulose is expected
      to reduce the 3-monthly Sick Fund cost in approximately 55% of patients and
      afford a cost-effective treatment in the remaining patients. Furthermore, the 3
      monthly Sick Fund cost of managing chronic idiopathic constipation among ambulant
      patients is expected to be reduced by approximately 50% if patients were
      initially treated by a GP instead of a specialist. In Belgium, laxatives are paid
      for by patients. Despite the difference in their acquisition cost, treating
      chronic idiopathic constipation with either macrogol 3350 or lactulose was found
      to be cost neutral from a patient's perspective. CONCLUSIONS: The true cost of
      managing chronic idiopathic constipation is impacted on by a broad range of
      resources and not only laxative acquisition costs. This study indicated that
      managing ambulant patients with chronic idiopathic constipation with macrogol
      3350 instead of lactulose is a cost-effective treatment from the Sick Fund's
      perspective and cost neutral from a patient's perspective.

PMID- 17523736
TI  - Trimetazidine Modified Release in the Treatment of Stable Angina : TRIUMPH
      StudyTRImetazidine MR in Patients with Stable Angina: Unique Metabolic PatH.
AB  - OBJECTIVE: To assess the clinical efficacy, safety and effects on quality of life
      of trimetazidine modified release (MR) in patients with stable angina. METHODS:
      This large, open-label, uncontrolled study was conducted in 906 patients with
      stable angina in the Russian Federation. Patients were treated for 8 weeks with
      trimetazidine MR (35mg tablet, twice a day) in addition to their conventional
      therapy. RESULTS: Overall 846 patients (516 men and 330 women) aged 58.7 +/- 9
      years completed the study. During the 8-week treatment period the number of
      angina attacks per week decreased continuously and significantly from 11.2 +/-
      0.4 to 3.6 +/- 0.2 (p < 0.0001). Concurrently, the number of short-acting nitrate
      tablets taken per week decreased from 11.9 +/- 0.8 to 3.4 +/- 0.2 (p < 0.0001).
      Patients' quality of life, assessed on the Seattle Angina Questionnaire, showed a
      significant improvement (p < 0.0001) for all five items evaluated: physical
      limitation increased from 50.7 +/- 0.7 to 61.0 +/- 0.6, angina stability improved
      from 57.6 +/- 0.9 to 92.5 +/- 0.7, angina frequency extended from 33.3 +/- 0.7 to
      55.6 +/- 0.8, treatment satisfaction increased from 62.3 +/- 0.7 to 77.4 +/- 0.5,
      and disease perception improved from 36.7 +/- 0.6 to 55.5 +/- 0.7. Adverse events
      were reported in 2.4% of patients (22/906) during the 8 weeks of treatment. No
      serious adverse events were reported. CONCLUSION: The results of this study
      suggest an improvement in clinical efficacy and in quality of life and a good
      tolerance of trimetazidine MR administered at a dose of 35mg twice a day for 8
      weeks in patients with stable angina.

PMID- 17523737
TI  - Bioequivalence study of two Ibuprofen formulations administered intravenously in
      healthy male volunteers.
AB  - OBJECTIVE: To compare the systemic bioavailability of two ibuprofen formulations,
      Pedea((R)) (ibuprofen intravenous [IV] formulation) and Imbun((R)) (ibuprofen
      intramuscular [IM] formulation) in 18 healthy male volunteers. METHODS: Each
      subject received a 5 mg/kg dose of ibuprofen base as a short 15-minute IV
      infusion as the Pedea((R)) ibuprofen IV formulation or as the reference
      Imbun((R)) IM formulation. Concentrations of R- and S-ibuprofen were measured by
      a validated HPLC method with a lower limit of quantification of 0.100 microg/mL.
      RESULTS: A single 5 mg/kg injection of Pedea((R)) was well tolerated. The most
      frequent adverse event was a mild to moderate burning sensation along the
      injection vein probably related to the study treatments.The maximum serum
      concentration (C(max)) of R- and S-ibuprofen ranged from 20 to 35 microg/mL with
      both formulations. No statistical differences were observed for either C(max) or
      area under the plasma concentration-time curve (AUC). 90% CIs calculated for
      C(max) and AUC from time zero to infinity (AUC(infinity)) of R-ibuprofen and S
      ibuprofen were included in the bioequivalence range 0.80-1.25. Based on
      AUC(infinity), the mean (SD) relative bioavailability of Pedea((R)) (ibuprofen IV
      formulation) versus the Imbun((R)) IM reference formulation was 1.06 (0.17) for R
      ibuprofen and 1.05 (0.08) for S-ibuprofen. CONCLUSION: This study showed that
      Pedea((R)) (test formulation) is bioequivalent to Imbun((R)) IM (reference
      formulation) for both R-ibuprofen and S-ibuprofen. The Imbun((R)) IM formulation
      (lyophilisate) could be replaced by the Pedea((R)) ready-to-use IV solution.
      Moreover, these results allow a comparison of safety and efficacy data previously
      generated with either formulation. Consequently, neonatologists, who previously
      used the IM formulation intravenously for the treatment of patent ductus
      arteriosus in preterm infants, will now be able to administer the new ready-to
      use IV solution of ibuprofen directly.

PMID- 17523738
TI  - Reduction of Propofol-Induced Pain through Pretreatment with Lidocaine and/or
      Flurbiprofen.
AB  - OBJECTIVE: Pain is a well recognised complication of propofol injection. The
      purpose of this study was to compare the efficacy of flurbiprofen, lidocaine and
      a combination of the two in reducing pain on injection of propofol. DESIGN:
      Prospective, randomised, double-blind, placebo-controlled study. SETTING:
      University hospital in Tsukuba City, Japan. PATIENTS AND INTERVENTIONS: 120
      patients, 56 males and 64 females, aged 20-66 years, scheduled for elective
      plastic surgery were included. Patients received intravenously either lidocaine
      20mg, flurbiprofen 50mg, both, or placebo (saline) accompanied by manual venous
      occlusion for 2 minutes, followed by administration of propofol 2 mg/kg into a
      dorsal hand vein (n = 30 in each group). A blinded researcher asked each patient
      to evaluate the pain score (0 = none, 1 = mild, 2 = moderate, 3 = severe) during
      propofol injection. MAIN OUTCOME MEASURES AND RESULTS: The incidence and
      intensity of pain was less in patients receiving lidocaine (27%, pain score 0
      [median]), flurbiprofen (43%, 0), or both (3%, 0) along with venous occlusion
      than in those receiving placebo (90%, 2) along with venous occlusion (p < 0.01).
      Combined lidocaine and flurbiprofen with venous occlusion was the most effective
      treatment (p < 0.05). No complications such as pain, oedema, wheal or flare
      response were observed at the injection sites within the first 24 hours after
      surgery. CONCLUSION: Combined lidocaine 20mg and flurbiprofen 50mg along with
      venous occlusion for 2 minutes was very effective for reducing pain on injection
      of propofol in patients scheduled for elective plastic surgery.

PMID- 17523739
TI  - Comparison of the Effect of Ribosomal Immunotherapy on Plasma Levels of Total IgE
      and Cytokines IL-4, IL-5, IL-12 and IFNgamma in Adult Atopic and Non-Atopic
      Patients during the Pollen Season.

PMID- 17523740
TI  - Effect of Ribosomal Immunotherapy on the Clinical Condition and Plasma Levels of
      Cytokines IL-4, IL-5, IL-12 and IFNgamma and Total IgE in Patients with Seasonal
      Allergy during the Pollen Season.

PMID- 17523741
TI  - Cerebral Blood Flow before and after Treatment with Amlodipine in Elderly
      Patients with Lacunar Infarction.

PMID- 17523742
TI  - Efficacy and Safety of Salmeterol/Fluticasone Propionate Combination Delivered by
      the Diskustrade mark or Pressurised Metered-Dose Inhaler in Children with Asthma.
AB  - BACKGROUND AND OBJECTIVE: Salmeterol and fluticasone propionate are well
      established in the treatment of childhood asthma, and their combination is
      effective in children aged 4-11 years. Asthma guidelines recommend that the
      inhaler device best suited to the individual should be used to administer asthma
      treatment. The aim of this study was to further evaluate the efficacy of
      salmeterol/fluticasone propionate combination (SFC) delivered by the Diskustrade
      mark (50/100mug, one inhalation twice daily) and compare it with that observed
      when SFC is delivered by a chlorofluorocarbon-free pressurised metered-dose
      inhaler (pMDI) [25/50mug, two inhalations twice daily] in children aged 4-11
      years with persistent asthma. PATIENTS AND METHODS: This equivalence study had a
      multicentre, randomised, double-blind, double-dummy, parallel-group design and
      comprised asthmatic children aged 4-11 years who required beclometasone
      (beclomethasone dipropionate) </=500 mug/day (or equivalent). After a 2-week run
      in using existing inhaled corticosteroid therapy, patients were randomised to
      receive SFC via Diskustrade mark (n = 213) or pMDI (n = 215, with 82% using a
      spacer) for 12 weeks. Salbutamol (Ventolin((R))) was provided for symptomatic
      relief. The primary endpoint was mean morning peak expiratory flow rate (PEF)
      recorded by patients during weeks 1-12. Secondary endpoints included other lung
      function parameters, day- and night-time symptoms, use of rescue medication and
      percentage of symptom- and salbutamol-free days. Adverse events and 12-hour
      overnight urinary cortisol concentrations were monitored to assess safety.
      RESULTS: Treatment with SFC, delivered by either device, was highly effective in
      improving patients' morning PEF and asthma symptoms. Over the whole study period,
      morning PEF (mean +/- standard error) improved by 37.7 +/- 3.1 L/min in the
      Diskustrade mark group and by 38.6 +/- 3.0 L/min in the pMDI group. The -0.9
      L/min difference between groups (95% CI -7.1, 5.4) was within the predefined
      criterion for equivalence of (i.e. -15, 15 L/min). The median percentage of
      symptom-free and rescue medication-free days and nights increased considerably in
      both groups. For all efficacy parameters assessed, improvement occurred for all
      age groups as early as weeks 1-4, and was sustained over the 12 weeks. Both
      Diskustrade mark and pMDI treatments were well tolerated and their safety
      profiles were comparable. CONCLUSION: SFC delivered via Diskustrade mark or pMDI
      was shown to be highly effective in asthmatic children aged 4-11 years. Children
      as young as 4 years were able to use the Diskustrade mark and pMDI effectively.
      The combination is clinically equivalent when administered via either device in
      this patient population. This means that both Diskustrade mark and pMDI (+
      spacer) are suitable for administration of SFC, which provides prescribers/users
      with a choice of device.

PMID- 17523743
TI  - Once-Daily Fluticasone Propionate is as Effective as Twice-Daily Treatment in
      Stable, Mild-to-Moderate Childhood Asthma.
AB  - OBJECTIVE: To test the hypothesis that once-daily treatment with fluticasone
      propionate is as effective as twice-daily treatment in children with well
      controlled asthma. DESIGN: Multicentre, randomised, double-blind, parallel-group
      study. SETTING: General practice, 86 UK centres. PATIENTS: 328 children with a
      diagnosis of asthma and a mean age of 10 years (range 4-16 years), mean duration
      of asthma of 5.5 years, and a mean percentage predicted forced expiratory volume
      in 1 second prior to randomisation of 93% were randomised. INTERVENTIONS:
      Patients entered a 4-week, open run-in period, receiving fluticasone propionate
      50mug twice daily via a Diskustrade mark inhalation device. Patients whose asthma
      was well controlled according to predefined criteria were randomised to receive
      either fluticasone propionate 100mug at night and placebo in the morning (once
      daily [od] group; n = 151) or fluticasone propionate 50mug twice daily (bd) [bd
      group; n = 177] for 8 weeks. MAIN OUTCOME MEASURES: Mean morning peak expiratory
      flow over the 8 weeks of treatment, recorded daily, adjusted for baseline, age,
      height and sex. RESULTS: The 90% CI for the treatment difference in morning peak
      flow (bd-od) in the intention-to-treat population was -1.9 to 5.3 L/min,
      demonstrating clinical equivalence between bd and od administration. Fifteen
      patients withdrew from the study due to asthma-related problems, ten patients
      from the od group and five from the bd groups (p = 0.10). Both groups remained
      well controlled in terms of lung function, symptoms and use of relief medication
      throughout the study. CONCLUSIONS: Once-daily treatment with fluticasone
      propionate 100mug at night is as effective as 50mug twice daily in children with
      well controlled mild-to-moderate asthma.

PMID- 17523744
TI  - Effect of a simple dose-escalation schedule on tramadol tolerability : assessment
      in the clinical setting.
AB  - OBJECTIVE: To assess the effect of a very simple dose-escalation schedule on
      tramadol tolerability in clinical practice. This schedule consists of starting
      treatment with sustained-release tramadol 50mg twice daily, and escalating the
      dose around 7 days later to 100mg twice daily. METHODS: Data from 1925
      outpatients with non-malignant chronic pain were collected in this multicentre,
      prospective, comparative, non-randomised, open, observational study. RESULTS: A
      total of 1071 patients (55.6%) were included in the dose-escalation group (50mg
      group) and 854 patients (44.4%) in the control group (sustained-release tramadol
      100mg twice daily; 100mg group). The proportion of patients who interrupted
      tramadol treatment due to the occurrence of adverse reactions was significantly
      lower in the 50mg group (5.6%) than in the 100mg group (12.6%) [p = 0.001]. In
      line with this, the proportion of patients who experienced at least one adverse
      reaction was significantly lower in the 50mg group (18.4%) than in the 100mg
      group (30.4%) [p = 0.001] and, interestingly, the two most frequently reported
      adverse reactions, nausea and dizziness, were found with a significantly lower
      frequency in the 50mg group (p < 0.001). Multivariate analysis showed that the
      risk of safety-related treatment cessations was 2.3 times higher in the 100mg
      group than in the 50mg group, and 2.2 times higher in females than in males. The
      two treatments were equally effective in reducing pain intensity (p = 0.121),
      measured as a reduction in pain score obtained by means of a visual analogue
      scale. CONCLUSION: The instauration of tramadol treatment, starting with
      sustained-release 50mg capsules twice daily and escalating the dose some days
      later to 100mg twice daily, was shown to be an effective and easy way to improve
      tramadol tolerability in clinical practice, whilst maintaining its analgesic
      efficacy.

PMID- 17523745
TI  - Dose conversion and cost effectiveness of erythropoietic therapies in
      chemotherapy-related anaemia : a meta-analysis.
AB  - OBJECTIVE: To estimate a dose-conversion ratio (DCR) between epoetin alfa (EPO)
      and darbepoetin alfa (DARB) and compare the costs of both drugs at the estimated
      DCRs using average wholesale prices (AWPs). METHODS: A search of PUBMED,
      CANCERLIT and references for papers and abstracts reporting on clinical trials of
      DARB or EPO for chemotherapy-related anaemia (CRA) identified 56 publications. A
      meta-analysis was conducted on the 12 eligible papers to estimate a DCR at which
      the two drugs were equally effective as measured by the area under the curve of
      haemoglobin (Hb) change (Hb AUC) at weeks 4 and 13. The DCR is based on the ratio
      of the coefficients of DARB and EPO doses in a regression of Hb AUC on those two
      variables, baseline Hb, Hb change calculation method, tumour type, and dosing
      frequency. Studies were frequency-weighted by the number of subjects. DCRs with
      confidence intervals (CIs) were calculated using a Monte-Carlo approach. Results
      from the regression were used to calculate DCRs for different dosing regimen
      comparisons - EPO three times weekly (TIW) versus DARB once weekly (QW), EPO TIW
      versus DARB once every 2 weeks (Q2W), EPO QW versus DARB QW, and EPO QW versus
      DARB Q2W. Relative cost effectiveness (RCE) was assessed by comparing drug costs
      at the estimated DCRs at $US 2003 AWPs [RCE = DCR . ($/U EPO)/($/mug DARB)].
      RESULTS: The regression results suggest an EPO QW : DARB QW DCR of 187 (95% CI
      183, 191). Depending on the assumed starting dose, the DCR ranges from 126 to 137
      for EPO TIW : DARB QW; from 128 to 139 for EPO TIW : DARB Q2W; and equals 191 for
      EPO QW : DARB Q2W. RCE was 2.0 for the main regression. CONCLUSION: The DCR of
      330 : 1 estimated for the 2004 Hospital Outpatient Prospective Payment System by
      the Centers for Medicare and Medicaid Services is greater than the DCRs estimated
      based on Hb AUC. The DCR estimated in the primary regression suggests that based
      on AWPs, EPO is 2.0 times more cost effective than DARB.

PMID- 17523746
TI  - Pharmacoeconomics of antiviral therapy for influenza in a Japanese hospital
      setting.
AB  - OBJECTIVES: We constructed a cost-effectiveness decision model to determine a
      hypothetical 'best treatment' pathway for patients presenting at our institution
      with influenza virus infection when the choice of treatment was either
      oseltamivir, zanamivir or a control therapy not active against influenza.
      METHODS: The decision model was constructed using DATA 3.5 for evaluating the
      cost-effectiveness analysis of neuraminidase inhibitors from the perspective of
      the healthcare payer. The time horizon was set at 14 days based on the general
      duration of influenza infection in Japan. Clinical outcomes were mainly derived
      from reports and guidance published by the National Institute for Clinical
      Excellence in the UK. Japan-specific cost parameters incorporated into the
      decision model were taken from the Medical Fee Point Survey conducted at St
      Luke's International Hospital in accordance with medical fee receipts kept at our
      institution. The study included four professionals and a supporter who gathered
      information required for the analysis. RESULTS: In otherwise healthy adults, cost
      savings of yen831.6 (approximately $US6.72; 2002 values) in the oseltamivir group
      and an increment in cost of yen40.5 (approximately $US0.33) in the zanamivir
      group were achieved in comparison with the control group. In contrast, an
      incremental cost of yen288.4 (approximately $US2.33) was incurred in the
      oseltamivir group versus the control group when at-risk patients were assessed,
      but cost savings of yen159.8 (approximately $US1.29) were achieved in the
      zanamivir group. As a result of cost-effectiveness and cost-utility analyses in
      otherwise healthy adults, oseltamivir dominated the control therapy because cost
      savings in the oseltamivir group were made. In the zanamivir group the cost was
      incremental and the Incremental Cost-Utility Ratio (ICUR) compared with the
      control group was about yen13 000 (approximately $US107.34)/quality-adjusted life
      year (QALY) gained. As a result of cost-effectiveness and cost-utility analyses
      in at-risk patients, in the oseltamivir group the cost was incremental and the
      ICUR compared with the control group was about yen230 000 (approximately
      $US2138.77)/QALY gained. As cost savings were made, zanamivir dominated the
      control therapy. CONCLUSION: While the cost effectiveness (from the perspective
      of a healthcare payer) of the neuraminidase inhibitors was superior to that of
      the control group in the treatment of otherwise healthy adults with influenza in
      our study, it seemed necessary to take other factors into consideration before
      recommending one agent over the other as a first-line therapy. On the other hand,
      we suggest that zanamivir is the drug of choice for use in at-risk patients, and
      we recommend, in the light of our results, that if zanamivir is not available
      another therapy should be given rather than oseltamivir. Since with influenza
      infections deaths and hospitalisations of at-risk patients impact on the Japanese
      community, decision-making on the appropriate therapy should take into account
      the particular patient group involved.

PMID- 17523747
TI  - Postoperative Melagatran/Ximelagatran for the Prevention of Venous
      Thromboembolism following Major Elective Orthopaedic Surgery : Effects of Timing
      of First Dose and Risk Factors for Thromboembolism and Bleeding Complications on
      Efficacy and Safety.
AB  - OBJECTIVES: To examine the influence of timing of postoperative initiation of
      subcutaneous melagatran followed by oral ximelagatran, and of risk factors for
      venous thromboembolism (VTE; including deep vein thrombosis [DVT] and pulmonary
      embolism [PE]) and bleeding complications, on the efficacy and safety of this
      regimen, compared with preoperative enoxaparin sodium, following total hip
      replacement (THR) or total knee replacement (TKR) surgery. DESIGN: Statistical
      analyses of efficacy and safety in subgroups of the METHRO III intention-to-treat
      population. MAIN OUTCOME MEASURES: Main efficacy outcome measures were major VTE
      (proximal DVT, PE or VTE-related death) and total VTE (distal or proximal DVT,
      fatal or non-fatal PE). The main safety outcome measures were blood transfusion,
      severe bleeding events, blood loss, bleeding-related adverse events and need for
      reoperation. RESULTS: In the combined THR and TKR population, melagatran
      initiated 4 - <8 hours postoperatively was non-inferior to enoxaparin sodium with
      respect to the risks of total VTE (absolute risk reduction [ARR] 0; 95%
      confidence interval [CI] -4.4, 4.4) and major VTE (ARR -0.63; 95% CI -2.94,
      1.67). The rate of major VTE was unaffected by the different risk factors. In the
      combined THR and TKR population, blood transfusion requirements were lower with
      melagatran/ximelagatran than enoxaparin sodium (odds ratio 0.83; 95% CI 0.71,
      0.96; p = 0.016). CONCLUSIONS: Melagatran/ximelagatran initiated 4 - <8 hours
      postoperatively provided a comparable level of protection against total and major
      VTE to preoperative enoxaparin sodium. Major VTE rates and safety were consistent
      across different patient subgroups. Subcutaneous melagatran followed by fixed
      dose oral ximelagatran offers an alternative to the standard European low
      molecular-weight heparin regimen in a wide range of patients.

PMID- 17523748
TI  - Clinical observations of sertindole in 53 hospitalised patients with psychotic
      disorders.

PMID- 17523749
TI  - Liposomal Amphotericin B and HIV-Associated Visceral Leishmaniasis : Concerns
      about Nephrotoxicity and Administration Schedule.

PMID- 17523750
TI  - Reform of prescription drug reimbursement and pricing in the German social health
      insurance market: a comparison of three scenarios.
AB  - We review regulation of two important parameters for third-party payers and
      manufacturers of prescription drugs: regulation of reimbursement and pricing. We
      find that centralised regulation of reimbursement and pricing prevails in the 15
      original EU member countries (EU-15) and in European Free Trade Association
      (EFTA) countries. Compared with countries such as Switzerland, The Netherlands,
      France and England, regulation in the German social health insurance system is
      rather unique. First, market approval is nearly always equivalent to
      reimbursement. Second, manufacturers are free to determine prices but internal
      reference prices restrict them from actually doing so for generics and
      therapeutic substitutes. In order to contain rising expenditures for prescription
      drugs in Germany, and to set incentives for physicians to consider the costs as
      well as the benefits of prescriptions, three reform scenarios are feasible. The
      first scenario maintains centralised reimbursement and centralised pricing; the
      second maintains centralised reimbursement but switches to decentralised pricing
      (similar to social health insurance in Israel and Medicare in the US). Third
      party payers would be able to negotiate with manufacturers about discounts and
      market shares for genetic and therapeutic substitutes. In the third scenario,
      pricing and reimbursement would be decentralised (similar to private health
      insurance in the US). We suggest that the second scenario is a viable compromise
      between consumer protection and a more competitive and cost-effective market for
      prescription drugs in German social health insurance and other similar markets
      for prescription drugs.

PMID- 17523751
TI  - Estimation, power and sample size calculations for stochastic cost and
      effectiveness analysis.
AB  - Various methods have been proposed to address uncertainty in economic evaluations
      of healthcare programmes. One approach suggested in the literature is to estimate
      separate confidence intervals for the incremental costs and effects of a new
      health programme in comparison with an existing programme. These intervals are
      then combined to generate a rectangular confidence region in the cost
      effectiveness plane that implicitly defines a corresponding confidence interval
      for the incremental cost-effectiveness ratio (ICER). The same approach has been
      used to calculate sample sizes and study power. This application of the rectangle
      method is consistent with the adoption of ICERs and a threshold as a decision
      rule, this being the most commonly used approach in empirical applications of
      cost-effectiveness analysis, as well as the one recommended by agencies that
      assess medical technology around the world. In this paper, we first outline the
      rectangle method, and then propose a modification that recognises that separate
      inferences are being drawn on the cost and effectiveness domains, and that
      corrects for multiple statistical comparisons. The confidence rectangle is
      otherwise too small, the corresponding confidence interval for the ICER is too
      narrow and sample sizes are under-estimated. Our modification corrects these
      problems. A further difficulty is that the placement of the confidence rectangle
      around the null value is somewhat arbitrary, and does not correspond to a unique
      value of ICERs. As a result, different values of sample size and power for the
      estimation of ICERs can be obtained, depending on the null values of the cost and
      effectiveness. We conclude that it is important to clearly identify the analytic
      goal in terms of estimating differential costs, differential effects or a
      combination of the two using the ICER index. These ideas are illustrated using
      numerical examples.

PMID- 17523752
TI  - A systematic review of economic evaluation literature in Thailand: are the data
      good enough to be used by policy-makers?
AB  - In many countries, including Thailand, there is an increasing impetus to use
      economic evaluation to allow more explicit and transparent healthcare priority
      setting. However, an important question for policy makers in low- and middle
      income countries is whether it is appropriate and feasible to introduce economic
      evaluation data into healthcare priority-setting decisions. In addition to
      ethical, social and political issues, information supply challenges need to be
      addressed. This paper systematically reviewed the literature on economic
      evaluation of health technology in Thailand published between 1982 and 2005. Its
      aim was to analyse the quantity, quality and targeting of economic evaluation
      studies that can provide a framework for those conducting similar reviews in
      other settings. The review revealed that, although the number of publications
      reporting economic evaluations has increased significantly in recent years,
      serious attention needs to be given to the quality of reporting and analysis.
      Furthermore, there is an absence of economic evaluation publications for 15 of
      the top 20 major health problems in Thailand, indicating a poor distribution of
      research resources towards the determination of cost-effective interventions for
      diminishing the disease burden of certain major health problems. If economic
      evaluation is only useful for policy makers when performed correctly and reported
      accurately, these findings depict information barriers to using economic
      evaluation to assist health decision-making processes in Thailand.

PMID- 17523753
TI  - Treatment interruptions and non-adherence with imatinib and associated healthcare
      costs: a retrospective analysis among managed care patients with chronic
      myelogenous leukaemia.
AB  - OBJECTIVES: Identify treatment interruptions and non-adherence with imatinib;
      examine the clinical and patient characteristics related to treatment
      interruptions and non-adherence; and estimate the association between treatment
      interruptions and non-adherence with imatinib and healthcare costs for US managed
      care patients with chronic myeloid leukaemia (CML). METHODS: This retrospective
      analysis utilised electronic healthcare claims data from a US managed care
      provider. Adult patients with CML (as determined by International Classification
      of Diseases, ninth revision, Clinical Modification [ICD-9-CM] diagnosis code)
      were identified who began treatment with imatinib from 1 June 2001 through 31
      March 2004. Treatment interruptions (i.e. failure to refill imatinib within 30
      days from the run-out date of the prior prescription) were identified during the
      12-month follow-up period. Medication possession ratio (MPR), calculated as total
      days' supply of imatinib divided by 365, was also examined. Healthcare costs
      (i.e. paid amounts for all prescription medications and medical services
      received, including health plan and patient liability) were examined in three
      ways: (i) total healthcare costs; (ii) total healthcare costs exclusive of
      imatinib costs; and (iii) total medical costs. All costs were converted to US
      dollars (2004 values) using the medical component of the Consumer Price Index.
      MPR was modelled using ordinary least squares regression. Presence of treatment
      interruptions was modelled using logistic regression. The association between MPR
      and healthcare costs was estimated using a generalised linear model specified
      with a gamma error distribution and a log link. All models included adjustment
      for age, gender, number of concomitant medications, starting dose of imatinib and
      cancer complexity. RESULTS: A total of 267 patients were identified. Average age
      was approximately 50 years, and 43% were women. Mean MPR was 77.7%, with 31% of
      patients having a treatment interruption. However, all of these patients resumed
      imatinib within the study period. In this population, MPR decreased as the number
      of concomitant medications increased (p = 0.002), and was lower among women (p =
      0.003), patients with high cancer complexity (p = 0.003) and patients with a
      higher starting dose of imatinib (p = 0.04). Women were approximately twice as
      likely as men to have a treatment interruption (p = 0.009), as were patients with
      a high cancer complexity (p = 0.03). After adjusting for the aforementioned
      covariates, MPR was found to be inversely associated with healthcare costs
      excluding imatinib (p < 0.001) and medical costs (p < 0.001). A 10% point
      difference in MPR was associated with a 14% difference in healthcare costs
      excluding imatinib and a 15% difference in medical costs. For example, patients
      with an MPR of 75% incur an additional 4072 US dollars in medical costs annually
      compared with patients with an MPR of 85%. CONCLUSIONS: Treatment interruptions
      and non-adherence with imatinib, both of which could lead to undesired clinical
      and economic outcomes, appear to be prevalent. Physicians and pharmacists should
      educate patients and closely monitor adherence to therapy, as improving adherence
      and limiting treatment interruptions may not only optimise clinical outcomes but
      also reduce the economic burden of CML.

PMID- 17523754
TI  - Cost effectiveness of oseltamivir treatment for patients with influenza-like
      illness who are at increased risk for serious complications of influenza:
      illustration for the Netherlands.
AB  - BACKGROUND: Oseltamivir is effective in the treatment of influenza. Utilisation
      in The Netherlands is limited, but increasing. OBJECTIVE: To estimate the cost
      effectiveness of oseltamivir treatment (vs symptom relief only) for patients with
      influenza-like illness (ILI) who are at increased risk for serious complications
      of influenza. METHODS: A cost-effectiveness analysis was used, building on a
      previously developed model (decision tree) that was applied for evaluating
      influenza vaccination and pandemic preparedness plans. Three patient subgroups
      were assessed (elderly patients [aged > or = 65 years] without chronic disease,
      elderly patients with chronic disease, and chronically ill, non-elderly
      patients). Inputs for the model were taken from various sources including a meta
      analysis. A societal perspective was adopted and costs were expressed in euro per
      life-year gained (year 2003 values). Life-years lost were discounted at 4% in
      accordance with Dutch guidelines. Deterministic and probabilistic sensitivity
      analyses were employed to assess the robustness of the results. RESULTS: For
      chronically ill patients with ILI, visits to the GP for oseltamivir treatment
      were cost saving. For non-chronically ill elderly patients, incremental cost
      effectiveness was estimated at 1759 euros per life-year gained. Cost savings and
      favourable cost effectiveness were robust in a deterministic and stochastic
      sensitivity analysis. CONCLUSION: Our model-based analysis suggests that at-risk
      people presenting with ILI to a GP could be offered oseltamivir at favourable
      cost effectiveness or even cost savings in the Dutch setting compared with
      symptom relief with analgesics only.

PMID- 17523755
TI  - Costs and benefits of direct-to-consumer advertising: the case of depression.
AB  - BACKGROUND: Direct-to-consumer advertising (DTCA) is legal in the US and New
      Zealand, but illegal in the rest of the world. Little or no research exists on
      the social welfare implications of DTCA. AIM: To quantify the total costs and
      benefits associated with both appropriate and inappropriate care due to DTCA, for
      the case of depression. METHODS: A cost-benefit model was developed using
      parameter estimates from available survey, epidemiological and experimental data.
      The model estimates the total benefits and costs (year 2002 values) of new
      appropriate and inappropriate care stimulated by DTCA for depression. Uncertainty
      in model parameters is addressed with sensitivity analyses. RESULTS: This study
      provides evidence that 94% of new antidepressant use due to DTCA is from non
      depressed individuals. However, the average health benefit to each new depressed
      user is 63-fold greater than the cost per treatment, creating a positive overall
      social welfare effect; a net benefit of >72 million US dollars. CONCLUSION: This
      analysis suggests that DTCA may lead to antidepressant treatment in 15-fold as
      many non-depressed people as depressed people. However, the costs of treating non
      depressed people may be vastly outweighed by the much larger benefit accruing to
      treated depressed individuals. The cost-benefit ratio can be improved through
      better targeting of advertisements and higher quality treatment of depression.

PMID- 17523756
TI  - Building bridges between academic research and policy formulation: when costing
      less means costing more.

PMID- 17523758
TI  - Candesartan treatment for peripheral occlusive arterial disease after stent
      angioplasty : a randomised, placebo-controlled trial.
AB  - OBJECTIVES: In this prospective, double-blind, placebo-controlled study we
      observed the influence of treatment with candesartan 8mg on restenosis rates
      after stent implantation into the femoral artery 6 months after percutaneous
      transluminal angioplasty (PTA). We hypothesised that angiotensin II type 1 (AT1)
      receptor blockade with candesartan would reduce restenosis rates by reducing
      angiotensin II-mediated intima hyperproliferation within the stented vessel
      segment in patients with peripheral occlusive disease. PATIENTS AND METHODS:
      Eighty-seven patients with peripheral occlusive arterial disease stage IIb who
      had been successfully treated with PTA and stent implantation were randomised to
      receive orally either candesartan 8mg (n = 44) or placebo (n = 43). Follow-up
      included evaluation of the degree of stenosis and thickness of the intima-media
      complex (primary endpoint). In addition, thickness of the interventricular
      septum, crurobrachial pressure ratios, and pain-free walking distance were
      determined (secondary endpoints). RESULTS: The degree of stenosis after 6 months
      was not significantly different between the groups studied (35.9 +/- 39.6% for
      candesartan vs 36.0 +/- 38.4% for placebo). Relevant restenosis including stent
      occlusions was found in nine patients (20.5%) in the candesartan group and in ten
      patients (23.3%) in the placebo group. The thickness of the intima-media complex
      6 months after stent implantation was 1.60 +/- 0.32mm in the candesartan group
      and 1.64 +/- 0.32mm in the placebo group (not significant). There were no
      differences in secondary endpoints between the treatment groups. Controls after 3
      months (20.9 +/- 33.6% for candesartan vs 27.6 +/- 38.3% for placebo; p = 0.39)
      and 9 months (44.1 +/- 40.8% for candesartan vs 47.7 +/- 37.2% for placebo; p =
      0.67) of therapy revealed a lower degree of stenosis in patients treated with
      candesartan. CONCLUSIONS: Although not significant, candesartan treatment tended
      to improve the prognostic benefits after stent implantation, suggesting that an
      antiproliferative effect after stenting may need higher doses than an
      antihypertensive effect of the drug. This hypothesis requires confirmation in
      further prospective studies with higher daily doses of candesartan, which are
      already in progress.

PMID- 17523759
TI  - Quality-of-Life Utility Values for Erectile Function and Sildenafil Treatment.
AB  - OBJECTIVE: The cost effectiveness of sildenafil remains controversial, due in
      part to questions about the magnitude and significance of changes in quality-of
      life utility values as a result of its use. Our objective was to measure
      utilities for present health and hypothetical erectile function scenarios in men
      with and without erectile dysfunction (ED) and to measure utilities in men with
      ED before and after treatment with sildenafil. SUBJECTS AND M ethods: Men with
      and without ED were recruited from a urologist's office. Subjects completed the
      International Index of Erectile Function (IIEF), the 12-Item Short-Form health
      survey (SF-12), and utility assessments (visual analogue scale [VAS], time
      tradeoff [TTO], and standard gamble [SG]) for their own present health and
      erectile function as well as for hypothetical scenarios of poor and very good
      erectile function. Exclusion criteria were cardiac illness history, current
      nitrate use, present sildenafil use, or inability to follow up. RESULTS: Eighty
      nine men without ED and 58 men with ED were recruited. Fifteen men with ED
      (25.9%) were prescribed sildenafil and completed at least one follow-up
      interview. Utilities for men with ED were significantly lower than men without ED
      by VAS (0.71 vs 0.84, p < 0.01) and TTO (0.89 vs 0.96, p < 0.01), but not by SG.
      Men without ED rated the poor erectile function scenario lower than men with ED;
      both groups rated the very good erectile function scenario similarly. Men without
      ED rated poor erectile function significantly lower than their present health
      (utility differences 0.34 for VAS, 0.08 for TTO and SG). In 15 men who gave
      ratings after sildenafil, significant changes were seen in IIEF scores, but not
      in utilities. CONCLUSION: Men with ED had lower VAS and TTO utilities than men
      without ED. Based on utility differences between present health and a poor
      erectile function scenario in men without ED, sildenafil would likely be
      considered cost effective from a societal perspective. However, sildenafil
      therapy may be less cost effective from a patient perspective, but conclusions
      are limited by the small group of men providing ratings after sildenafil therapy.
      Very good erectile function is highly valued by men regardless of their erectile
      function status.

PMID- 17523760
TI  - Pharmacokinetic considerations in determining the terminal elimination half-lives
      of bisphosphonates.
AB  - BACKGROUND AND OBJECTIVE: Bisphosphonates are commonly used to treat and prevent
      osteoporosis. These compounds have unusual pharmacokinetic characteristics
      because they bind strongly to bone, and a portion becomes buried under newly
      formed bone. Once incorporated into bone tissue, the subsequent release during
      bone remodeling is probably the rate-limiting step in the terminal elimination of
      bisphosphonates. Because of this unique property of bisphosphonates,
      pharmacokinetic studies with insufficient lengths of follow-up might entirely
      miss the true terminal elimination phase. A terminal half-life (t((1/2)gamma)) of
      approximately 11 years, similar to that of calcium and other minerals in bone,
      was reported from an 18-month study of alendronic acid in postmenopausal women
      with osteoporosis. We are not aware of any other published reports in which the
      elimination of a bisphosphonate has been followed for more than a few weeks post
      dose. The purpose of the present study was to reanalyse the alendronic acid data
      to examine the effect of truncating the length of follow-up on the calculated
      t((1/2)gamma). PATIENTS AND METHODS: Twenty-one postmenopausal women with
      osteoporosis (mean age 66 years) received intravenous alendronic acid 30mg over 4
      consecutive days (7.5 mg/day), and urinary excretion of alendronic acid was
      monitored over the following 18-24 months. Terminal elimination half-life was
      originally calculated by log-linear regression of the percentage retained versus
      time curve between days 240 and 540 and substituting the slope of the regression
      line into the equation, t((1/2)gamma) = -log 2/slope. These data were reanalysed
      based on the period up to 30 days. RESULTS: Data were sufficient for analysis of
      pharmacokinetics in 11 patients. A mean t((1/2)gamma) of approximately 11 years
      was reported previously, based on analysis of data between days 240 and 540.
      Recalculating the 'terminal' half-life of alendronic acid using only data from
      the first 30 days resulted in an 'observed' half-life of only 11 days.
      CONCLUSION: This analysis illustrates the importance of sufficient length of
      follow-up to accurately characterise the true terminal elimination half-life of
      bisphosphonates. The relatively short (expressed in units of days rather than
      years) terminal elimination half-lives reported for some bisphosphonates based on
      only 30 days of follow-up or less are likely to substantially underestimate the
      true terminal elimination half-lives.

PMID- 17523761
TI  - Pharmacokinetics of escalating doses of intravenous repinotan in healthy male
      volunteers.
AB  - OBJECTIVE: To investigate the pharmacokinetics of intravenous (IV) repinotan, a
      potent selective full serotonin (5-HT(1A)) receptor agonist, after administration
      of escalating doses/infusion rates to healthy volunteers with extensive or poor
      metaboliser phenotype, and to compare weight-adjusted (mg/kg) to fixed (mg/day)
      dosing regimens. SUBJECTS AND M ethods: The pharmacokinetic profile of IV
      repinotan was evaluated in healthy male volunteers. In eight studies, extensive
      metabolisers (EMs) and poor metabolisers (PMs) identified by sparteine
      phenotyping were given IV repinotan at doses of 5-100microg over 1 hour or 200
      1000microg over 4 hours. In two additional studies of EMs and PMs, IV repinotan
      was administered as a weight-adjusted dose of 1 microg/kg/h for 24 hours.
      Repinotan plasma concentrations were measured for determination of non
      compartmental pharmacokinetic parameters. RESULTS: Sixty-five male subjects (54
      EMs and 11 PMs) were valid for pharmacokinetic evaluation. During continuous IV
      infusion, a steady-state repinotan plasma level was reached within 4-5 hours in
      EMs, and the elimination half-life was 1 hour. Pharmacokinetics were linear in
      EMs across a wide range of doses (5-2250microg) and infusion rates (5-250
      microg/h). Repinotan clearance was correlated with the log metabolic ratio (MR)
      of sparteine as an indicator for cytochrome P450 (CYP)2D6 phenotype, and subjects
      phenotyped as PMs had reduced clearance, resulting in longer elimination half
      lives (up to a mean value of 11 hours) and increased peak plasma concentrations
      and area under the concentration-time curve values. Bodyweight was not a
      significant covariable for clearance and the interindividual variability in
      clearance was not reduced after normalisation to bodyweight. Repinotan was well
      tolerated at infusion rates up to 150 microg/h (EMs), and no clinically relevant
      safety issues were reported. CONCLUSION: Repinotan demonstrates linear
      pharmacokinetics in EMs for CYP2D6, who constitute about 93% of the Caucasian
      population. Repinotan clearance is correlated with CYP2D6 phenotype and reduced
      in PMs. Bodyweight does not appear to be a major determinant of its
      pharmacokinetic variability and a bodyweight-adjusted dosing regimen is not
      warranted. Further studies should be performed in patients to investigate whether
      the tolerability profile of repinotan is comparable to that observed in healthy
      volunteers.

PMID- 17523762
TI  - Effect of gender and age on the pharmacokinetics of repinotan.
AB  - OBJECTIVE: Repinotan hydrochloride (repinotan) is a selective, high-affinity,
      full serotonin receptor agonist at the 5-HT(1A) subtype that is undergoing
      clinical development in acute stroke. To investigate whether gender is an
      important covariable for repinotan pharmacokinetics, two studies were performed
      in subjects of different age and gender who had been phenotyped as extensive
      metabolisers for cytochrome P450 (CYP)2D6 using dextromethorphan as model
      substrate. SUBJECTS AND METHODS: Both studies were placebo-controlled, double
      blind, randomised, parallel-group studies. Study I was conducted in six healthy
      young males, five healthy elderly males, and four healthy elderly females
      receiving a continuous intravenous (IV) infusion of repinotan 0.45 microg/kg/h or
      placebo for a duration of 12 hours. Study II was performed in healthy elderly
      male and female volunteers aged >/=65 years with 67 subjects receiving repinotan
      and 34 receiving placebo. Subjects received a 12-hour infusion of repinotan at
      doses of 0.1, 0.3, 0.5, 1.0, 2.0 or 3.0 microg/kg/h. RESULTS: Following IV
      infusion, the steady-state plasma concentration (C(ss)) for repinotan was reached
      after 4-6 hours consistent with its half-life of 0.8-1.8 hours. In both male and
      female subjects, the volume of distribution at steady-state and plasma clearance
      (CL) were independent of dose, indicating linear pharmacokinetics and dose
      proportionality for area under the concentration-time curve (AUC) and peak plasma
      concentration (C(max)) over the dose range of 0.1-3.0 microg/kg/h. Compared with
      elderly subjects, repinotan CL was unchanged in a subgroup of young subjects. The
      pooled evaluation of elderly subjects (n = 67) showed that gender had no
      influence on the pharmacokinetics of repinotan. The ratios male : female and
      their 90% CIs were: 0.91 (0.789, 1.052) for dose/bodyweight-normalised C(max)
      (C(max,norm)), 0.95 (0.808, 1.110) for half-life, 0.97 (0.900, 1.044) for V(ss,)
      and 1.11 (0.923, 1.336) for CL. CONCLUSION: These results indicate that gender
      does not affect the pharmacokinetics of repinotan in healthy subjects whose age
      (>/=65 years) was representative of the target patient population for repinotan
      in acute stroke.

PMID- 17523763
TI  - A survey of the quality of generic clarithromycin products from 18 countries.
AB  - OBJECTIVE: This study compared the quality of 65 generic clarithromycin products
      manufactured in 18 countries with that of the innovator product. DESIGN: To
      assess quality, the generic products were examined visually, assayed by high
      pressure liquid chromatography for clarithromycin content and impurities, tested
      for dissolution properties, and compared with the innovator product manufactured
      by Abbott Laboratories. RESULTS: This survey found that many generic
      clarithromycin products were not equivalent to the innovator product and many of
      these generic products fell short of the approved specifications developed for
      the innovator product. Overall, 9% (6 of 65) of all generic tablets tested failed
      to contain between 95% and 105% of the clarithromycin claimed in the label, thus
      falling short of the approved registered specification for the innovator product.
      Seventeen percent (1 of 6) of tablets from Latin America (LA), 8% (3 of 38) of
      tablets from the Asia, Africa, Pacific (AAP) region, and 10% (2 of 21) of tablets
      from Europe did not contain the amount of clarithromycin drug content claimed in
      the label. A total of 34% (17 of 50) of the generic products tested released less
      drug in 30 minutes than did the innovator tablets. Although the majority of these
      generic products met the dissolution specification requiring that 80% of the drug
      must dissolve in 30 minutes, one generic product failed to meet this
      specification with 68% of drug dissolving in 30 minutes. Moreover, 19% (12 of 65)
      of all the generic products tested exceeded the Abbott Laboratories' 3% limit for
      total impurities in bulk drug, and 30% (20 of 65) exceeded the Abbott
      Laboratories' 0.8% limit for the known impurity 6,11 di-O-methyl erythromycin A.
      CONCLUSIONS: These results demonstrated that generic tablets are often not
      comparable in vitro to the innovator product. These findings suggest that results
      achieved with branded clarithromycin (Abbott Laboratories) should not be
      extrapolated to generic products. In vivo studies would be needed to determine
      the clinical relevance of these findings.

PMID- 17523764
TI  - Predicting and establishing the clinical efficacy of a histamine h(1)-receptor
      antagonist : desloratadine, the model paradigm.
AB  - Antihistamines are well established as a mainstay for treating allergic diseases,
      including seasonal and perennial allergic rhinitis as well as other conditions,
      such as chronic idiopathic urticaria. The development of new antihistamines is a
      multistage process that includes in vitro and in vivo assessments of the
      antihistaminic, anti-inflammatory and antiallergic properties of new therapies.
      Results of these assessments are critical for predicting and establishing the
      clinical efficacy of an antihistamine. The focus of this article is to review the
      investigational methods used to assess the efficacy, safety and tolerability of
      newer histamine H(1)-receptor antagonists. Desloratadine, a new-generation H(1)
      receptor antagonist, was chosen to illustrate the use of this model paradigm.
      Data obtained from two large observational studies are presented, confirming
      results obtained from clinical trials that the in vitro inhibition of release of
      inflammatory mediators such as histamine, prostaglandins, leukotrienes and the
      reduction of secretion of cytokines such as IL-4 and IL-13 at physiological
      concentrations is reflected in increased efficacy, particularly upon nasal
      obstruction. A recent discovery that des- loratadine inhibits nuclear factor
      kappaB may be the underlying explanation for much of this extra anti-inflammatory
      activity.

PMID- 17523765
TI  - High-Dose Torasemide is Equivalent to High-Dose Furosemide with Hypertonic Saline
      in the Treatment of Refractory Congestive Heart Failure.
AB  - OBJECTIVE: A randomised, double-blind study was performed to evaluate the effects
      of the combination of high-dose torasemide and hypertonic saline solution (HSS)
      infusion versus high-dose furosemide (frusemide) and HSS in the treatment of
      refractory New York Heart Association class IV congestive heart failure (CHF).
      MATERIALS AND METHODS: Eighty-four patients (55 males, 29 females) with
      refractory CHF, aged 55-84 years, with an ejection fraction <35%, serum
      creatinine <2 mg/dL, blood urea nitrogen </=60 mg/dL, a reduced urinary volume
      and a low natriuresis, were randomised to two groups. Group 1 (27 males, 15
      females) received an intravenous infusion of furosemide 500mg plus HSS (150mL of
      1.4-4.6% sodium chloride) twice daily in 30 minutes. Group 2 (28 males, 14
      females) received torasemide 200mg twice daily plus HSS during a period lasting 4
      8 days. Physical examination, measurement of bodyweight, blood pressure, heart
      rate, evaluation of signs of CHF, and serum and urinary parameters were
      controlled daily during hospitalisation. Chest x-ray, ECG and echocardiogram were
      obtained at entry, during hospitalisation and at discharge. During the treatment
      and after discharge the daily dietary sodium intake was 120 mmol, with a fluid
      intake of 1.0-1.5L in both groups. Bodyweight and 24-hour urinary volume, serum
      and urinary laboratory parameters, until reaching a compensated state, were
      controlled daily, when intravenous furosemide and torasemide were replaced with
      oral furosemide administration only (250-500mg twice daily). After discharge the
      double-blind design was discontinued and the subsequent period was an open-label
      study with furosemide only; the patients were followed up as outpatients weekly
      for the first 3 months and subsequently once a month. RESULTS: Baseline clinical
      characteristics of patients were similar in both groups. A significant increase
      in daily diuresis and natriuresis was observed in both groups. No difference was
      observed in serum sodium or potassium. Bodyweight was reduced in both groups.
      Blood pressure values decreased, and heart rate was corrected to normal values in
      both groups. In the follow-up period (12 +/- 3.9 months), 17 patients were re
      admitted to the hospital for heart failure. Thirteen patients died during follow
      up. CONCLUSION: We conclude that high-dose torasemide is equivalent to high-dose
      furosemide in the treatment of refractory CHF.

PMID- 17523766
TI  - Zofenopril versus Lisinopril in the Treatment of Essential Hypertension in
      Elderly Patients : A Randomised, Double-Blind, Multicentre Study.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors have been proposed as first
      choice drugs for antihypertensive therapy in elderly subjects because of their
      demonstrated efficacy and safety. However, no information is currently available
      on the use of zofenopril in elderly hypertensive patients. OBJECTIVE: To assess
      the efficacy and safety of zofenopril (30 or 60mg once daily) compared with
      lisinopril (10 or 20mg once daily). PATIENTS AND METHODS: Patients aged >/=65
      years with mild to moderate essential hypertension (sitting diastolic blood
      pressure [DBP] >/=90mm Hg and </=110mm Hg) were included in the study. They were
      randomised to receive either zofenopril 30mg or lisinopril 10mg. Blood pressure
      and heart rate were measured at baseline and after 4 and 12 weeks of treatment.
      Patients underwent electrocardiography and evaluation of laboratory parameters at
      baseline and after 12 weeks. Ambulatory blood pressure monitoring (ABPM) was also
      performed at baseline and after 12 weeks. After 4 weeks drug doses were doubled
      in patients whose sitting DBP was >/=90mm Hg. The primary endpoint was to achieve
      sitting DBP values <90mm Hg or a reduction of sitting DBP >10mm Hg after 12 weeks
      of treatment. RESULTS: 181 patients were randomised to treatment and 164 patients
      completed the study. Thirty-three patients were included in the analysis of 24
      hour blood pressure monitoring. The percentage of patients with normalised
      sitting DBP (<90mm Hg) and the rate of treatment responders (reduction of sitting
      DBP >/=10mm Hg) were not significantly different between the two treatment groups
      (normalised: zofenopril 81.3% vs lisinopril 76.7%; responders: zofenopril 74.7%
      vs lisinopril 77.8%). At the end of the treatment sitting DBP was not
      significantly different between the two treatment groups (zofenopril 82.2 +/-
      6.6mm Hg vs lisinopril 82.0 +/- 7.8mm Hg). Eight percent of patients experienced
      adverse events in the zofenopril group and 9% in the lisinopril group. A small
      percentage of adverse events (4%) was related to treatment and reported in the
      zofenopril group. CONCLUSIONS: In elderly hypertensive patients, treatment with
      zofenopril was effective and well tolerated. Efficacy and safety were comparable
      with those of lisinopril.

PMID- 17523767
TI  - Nebulised L-epinephrine and steroid combination in the treatment of moderate to
      severe croup.
AB  - OBJECTIVE: To compare the effectiveness of nebulised L-epinephrine in combination
      with systemic or nebulised corticosteroid with that of cool mist and systemic
      corticosteroids in the treatment of moderate to severe croup. PATIENTS AND
      METHODS: Children were eligible for study if they presented to the emergency
      department with a moderate to severe croup. Patients were randomly assigned to
      three groups: group 1, cool mist and intramuscular dexamethasone (n = 26); group
      2, nebulised L-epinephrine and intramuscular dexamethasone (n = 31); group 3,
      nebulised L-epinephrine and nebulised budesonide (n = 19). The croup score, vital
      signs and oxygen saturation were assessed before and after medication. Adverse
      events, additional L-epinephrine and hospitalisation were recorded. RESULTS: Age,
      sex, initial croup score and vital signs were similar in all groups. Croup scores
      were significantly decreased over time in all treatment groups and this decrease
      was very evident at 30 minutes (p < 0.05). Croup scores of groups 2 and 3 were
      significantly lower than those of group 1 at 30 and 60 minutes but no difference
      was observed between groups 2 and 3 at these timepoints. The numbers of patients
      who had croup scores <2 at 30 and 60 minutes were higher in groups 2 and 3 than
      group 1 (p = 0.004 and p = 0.032, respectively). More patients in group 1
      received additional L-epinephrine treatments (p = 0.014). Changes in vital signs
      were not different among groups when assessed over time (p > 0.05). CONCLUSIONS:
      This study demonstrated that with early combination treatment, croup scores
      improved rapidly and hospitalisation rates were low. Patients with moderate to
      severe croup presenting to the emergency department should receive nebulised L
      epinephrine in combination with intramuscular dexamethasone or nebulised
      budesonide. No significant adverse effects were observed with L-epinephrine. The
      use of L-epinephrine has been proposed instead of racemic epinephrine in patients
      with moderate to severe croup because it is efficacious, well tolerated, less
      expensive and more readily available in many countries.

PMID- 17523768
TI  - A Randomised Crossover Study Comparing Ramosetron plus Dexamethasone with
      Ramosetron Alone in the Prevention of Cisplatin-Induced Emesis.
AB  - OBJECTIVE: To assess the efficacy and tolerability of a combination of ramosetron
      and dexamethasone compared with ramosetron alone in the prevention of cisplatin
      induced emesis. DESIGN: Prospective, randomised, single-blind, crossover study.
      PATIENTS: Thirty-four chemotherapy-naive patients with stomach cancer or sar-coma
      scheduled to receive two consecutive courses of cisplatin-based chemo-therapy.
      INTERVENTIONS: Patients were randomised to receive ramosetron (0.3mg
      intravenously [IV] on day 1 then 0.1mg orally [PO] once daily on days 2-6) either
      with or without dexamethasone (20mg IV on days 1-6). Those who completed the
      first chemotherapy cycle returned for a second cycle after 4 weeks and were
      crossed over to the alternate antiemetic treatment. RESULTS: In the first 24
      hours, complete response was achieved in 84.8% of patients receiving ramosetron
      plus dexamethasone and in 59.4% of patients receiving ramosetron alone (p =
      0.014). Furthermore, the combination ramosetron plus dexamethasone was
      significantly more effective in terms of time to first episode of vomiting and
      patient's preference. On day 2, patients who received ramosetron plus
      dexamethasone had a higher complete response rate than those who received
      ramosetron alone (p = 0.047). Adverse events were mild with no significant
      differences between the two groups. CONCLUSIONS: The combination of ramosetron
      plus dexamethasone was superior to ramosetron alone in preventing cisplatin
      induced acute emesis. It is highly recommended that a combination of ramosetron
      plus dexamethasone rather than ramosetrone alone be given to patients receiving
      cisplatin-containing chemo-therapy.

PMID- 17523769
TI  - Bioequivalence and rapid absorption of zolmitriptan nasal spray compared with
      oral tablets in healthy Japanese subjects.
AB  - BACKGROUND AND OBJECTIVE: Oral zolmitriptan is highly effective in the acute
      treatment of migraine. However, nausea and vomiting during attacks may limit the
      usefulness of oral medications. An alternative, nasal spray, formulation has been
      developed that demonstrates good efficacy, high tolerability and a very fast
      onset of action. This study assessed the pharmacokinetics and bioavailability of
      zolmitriptan and its active metabolite 183C91 in healthy Japanese subjects
      following single-dose (2.5 or 5mg) oral or intranasal administration. METHODS:
      This was a single-centre, open-label, randomised, crossover study. Forty-eight
      subjects each received one oral and one intranasal dose of 2.5 or 5mg
      zolmitriptan, with a 72-hour washout period between doses. Blood was drawn at
      various timepoints from 2 minutes to 15 hours post-dose and urine was collected
      over the course of the study; samples were analysed for zolmitriptan and 183C91,
      from which pharmacokinetic parameters were calculated. RESULTS: Zolmitriptan was
      detected in plasma 2 minutes after intranasal administration in the majority of
      subjects (~75%) compared with 10 minutes after oral administration. The
      intranasal : tablet ratio for zolmitriptan area under the concentration-time
      curve from time zero to infinity was 0.924 (90% CI 0.826, 1.033) and 0.960 (90%
      CI 0.865, 1.066) for the 2.5 and 5mg doses, respectively. Other pharmacokinetic
      parameters were similar between the two formulations. While 183C91 appeared in
      the plasma concurrently to zolmitriptan after oral dosing, its appearance was
      delayed to approximately 30 minutes after intranasal dosing. Zolmitriptan was
      safe and well tolerated at both doses. CONCLUSIONS: The rapid absorption of
      zolmitriptan nasal spray may explain the faster relief from migraine reported in
      patients compared with oral zolmitriptan.

PMID- 17523770
TI  - Comparison of the effect of low-dose ropivacaine and lidocaine in intravenous
      regional anaesthesia : a randomised, double-blind clinical study.

PMID- 17523771
TI  - Melaena following Use of the Cholinesterase Inhibitor Rivastigmine.

PMID- 17523772
TI  - Quality of life in sexually active men with symptomatic benign prostatic
      hyperplasia : effects of treatment.
AB  - Quality of life (QOL), sexuality in particular, has become an important
      consideration in treatment decisions for men with lower urinary tract symptoms
      (LUTS) related to benign prostatic hyperplasia (BPH). To determine the impact of
      these conditions on sexual function and QOL in older men, this article provides a
      review of clinical data on the relationship between sexual dysfunction and
      symptom severity, effective clinical assessment, treatment options, and the
      influence of current therapies on sexual function and QOL. The various symptoms
      of BPH can adversely affect sexual functioning and therefore QOL. Moreover, there
      may be a direct association between symptom severity and sexual dysfunction that
      may affect QOL.Patients base their decisions regarding treatment choices for BPH
      more on anticipated relief of lower urinary tract symptoms and improved QOL
      (including sexual functioning) than on improvements in physical measures.
      Although medications and surgery may relieve LUTS, sexual dysfunction is a common
      adverse result. Newer pharmacological interventions such as specific alpha
      adrenergic blocking agents like tamsulosin may help improve sexual function and
      QOL in men with symptomatic BPH.

PMID- 17523773
TI  - Short-term safety and tolerability of double-dose salmeterol/fluticasone
      propionate in adult asthmatic patients.
AB  - INTRODUCTION: The incidence of asthma exacerbations in patients receiving
      salmeterol/fluticasone propionate (Seretidetrade mark or Advair((R))) is low.
      However, when asthma control deteriorates, clinicians may instruct patients to
      double the dose of their inhaled corticosteroid medication for a short period.
      The purpose of this study was to demonstrate that doubling the dose of
      Seretidetrade mark for a period of 2 weeks in subjects with persistent asthma is
      safe and well tolerated. METHODS: This randomised, double-blind, parallel-group
      study was conducted in primary-care centres. Adults with a post-bronchodilator
      forced expiratory volume in 1 second (FEV(1)) of >/=70% predicted were stratified
      to receive a single dose of Seretidetrade mark 50mug/100mug, 50mug/250mug or
      50mug/500mug twice daily from a Diskustrade mark inhaler for a 4-week run-in
      period, dependent on the dose of inhaled corticosteroid on entry. Subjects were
      then randomised to receive either an extra inhalation of the same dose of
      Seretidetrade mark received during the run-in (double dose) or an inhalation of
      matching placebo (single dose) for 14 days in a 2 : 1 ratio. Subjects were asked
      to record any adverse events, morning and evening heart rate (HR), peak flow and
      relief medication use in daily record cards. The primary endpoint was tremor as
      perceived by the subject. Clinic evaluations included HR, 12-lead ECG, and
      potassium and glucose levels. RESULTS: 110 and 208 subjects received single- and
      double-dose Seretidetrade mark, respectively. Only one subject experienced
      tremor. This was classified as mild and occurred in a subject receiving double
      dose Seretidetrade mark (50mug/100mug). There was no difference between the
      treatment groups in the incidence of tremor (difference <1%; 95% CI -6, 8). Other
      salmeterol-related adverse events (palpitations, muscle cramps and headache) and
      fluticasone propionate-related events (oral candidiasis and hoarseness) occurred
      in a similar percentage of subjects in each treatment group. The treatment
      differences for morning and evening HR measurements showed small differences
      between the two groups (<2 beats/min). The adjusted mean treatment difference
      (double dose - single dose) in morning HR was 1.1 beats/min (95% CI 0.2, 2.0) and
      evening HR was 0.9 beats/min (95% CI 0.1, 1.7). Seven percent of subjects
      receiving single-dose Seretidetrade mark and 8% receiving double-dose
      Seretidetrade mark had a QTc change from baseline in the interval 30-59 msec. No
      increases above 59 msec were seen in either group. There were no clinically
      significant changes from baseline for potassium levels. Two percent of subjects
      in the single dose and <1% in the double-dose group had a change from a non
      clinically significant baseline blood glucose assessment to a clinically
      significant abnormality at the end of treatment. CONCLUSION: In circumstances in
      which a physician may be considering doubling the dose of Seretidetrade mark for
      a short period of time in adult asthmatics, this study demonstrates that doubling
      the dose for a period of 2 weeks is safe and well tolerated.

PMID- 17523774
TI  - Switching of H(2)-Receptor Antagonists to Over-the-Counter Status in Finland :
      Implications for Consumption and Adverse Effects.
AB  - OBJECTIVE: To evaluate the consumption and safety of H(2)-receptor antagonists
      after switching ranitidine and famotidine to over-the-counter (OTC) status.
      METHODS: The Finnish drug consumption data, based on the sales of medicines, and
      the national register for adverse drug reactions (ADRs) from 1990 to 2003 were
      used. We studied the consumption of H(2)-receptor antagonists, proton pump
      inhibitors, sucralfate and antacids (A02BA, A02BC, A02BX02 and A02A,
      respectively, according to the Anatomical Therapeutic Chemical [ATC]
      classification). We compared the ADRs of H(2)-receptor antagonists with proton
      pump inhibitors. RESULTS: The total consumption of medicines for the treatment of
      peptic ulcer disease and gastro-oesophageal reflux disease increased more than 2
      fold from 1990 to 2003 (from 12.8 daily defined doses [DDD]/1000 inhabitants/day
      to 29.6 DDD/1000 inhabitants/day). Initially, switching ranitidine and famotidine
      to OTC status in 1996 increased their consumption. Since 1998, proton pump
      inhibitors have been the most commonly used drug group for the treatment of
      peptic ulcer and gastro-oesophageal reflux disease in Finland. In 2003, the
      consumption of proton pump inhibitors was 75% (22.2 DDD/1000 inhabitants/day) of
      the total consumption of drugs for the treatment of peptic ulcer and gastro
      oesophageal reflux disease. Switching ranitidine and famotidine to OTC status did
      not affect the number of reported adverse reactions to these drugs. CONCLUSIONS:
      According to information collected from the Finnish consumption and ADR
      databases, H(2)-receptor antagonists are very often used in self-medication and
      they do not have serious adverse effects. However, the total number of reports
      concerning these ATC groups in the national ADR database is not very high, and
      therefore patient-based surveys are needed to verify this finding.

PMID- 17523775
TI  - Docetaxel as single-agent treatment in elderly patients with advanced breast
      cancer.
AB  - OBJECTIVE: To assess the efficacy and safety profile of docetaxel, as a single
      agent, in the treatment of elderly patients with advanced breast cancer. METHODS:
      Twenty-eight patients, with a median age of 72 (range 66-84) years, were included
      in the study and received docetaxel (50-100 mg/m(2)) every 3-4 weeks as first- or
      second-line treatment of advanced breast cancer. Granulocyte colony-stimulating
      factor (G-CSF) was administered as primary prophylaxis in 97% of cycles. RESULTS:
      The overall response rate was 50% (95% CI 32, 69). The median time to disease
      progression was 10.7 months (95% CI 10.0, 11.5), and the median overall survival
      was 26.6 months (95% CI 16.6, 36.7). Neutropenia was the most frequent grade 3/4
      toxicity (18% of patients and 5% of cycles). There was just one case of febrile
      neutropenia that resulted in toxic death. Severe neutropenia only occurred in
      patients who did not receive G-CSF support from the start of the study treatment.
      Vomiting was the most frequent grade 3/4 non-haematological toxicity (11% of
      patients and 2% of cycles). CONCLUSION: Docetaxel as a single agent is active in
      elderly patients with advanced breast cancer. The use of prophylactic G-CSF
      allowed the administration of high doses of docetaxel with minimal
      myelosuppression.

PMID- 17523776
TI  - Efficacy of supplemental anti-inflammatory therapy with fenspiride in chronic
      obstructive and nonobstructive bronchitis.
AB  - OBJECTIVE: The objective of this randomised, nonblind study was to assess the
      efficacy of fenspiride as complementary anti-inflammatory therapy in combination
      with ipratropium bromide in patients with chronic bronchitis (CB). A comparison
      was made with ipratropium bromide alone, the generally accepted standard therapy
      for CB. METHODS AND SUBJECTS: The study population comprised 20 patients with
      chronic obstructive bronchitis (COB) and 60 patients without signs of
      obstruction. Fifty-one males (64%) and 29 females (36%) aged from 25 to 65 years
      were studied over a 6-month treatment period. Combined therapy with fenspiride
      (160 mg/day) and ipratropium bromide (160 mug/day) was prescribed to 39 patients
      (28 with CB and 11 with COB) for 6 months, and monotherapy with ipratropium
      bromide (160 microg/day) was prescribed for 41 patients (32 with CB and nine with
      COB). RESULTS: The combined therapy group had a reduced intensity of dyspnoea,
      improvements in sputum nature and quantity of exudation, and a reduced intensity
      of coughing. The monotherapy group showed reductions in sputum exudation and
      cough intensity. Improvements in lung respiratory function were observed in both
      groups, but were greater in the combined therapy group of patients. Reduced
      cytosis, percentage and absolute content of neutrophils, and absolute content of
      lymphocytes and eosinophils in induced sputum were observed with CB patients in
      the combined therapy group. A reduced content of lymphocytes and an increase in
      macrophages were observed with CB patients in the monotherapy group. A
      significant decline in tumour necrosis factor (TNF)-alpha content in sputum was
      observed with both therapeutic regimens, although a statistically significant
      decline in serum TNFalpha (10.85 ng/L to 5.58 ng/L; p = 0.03) and reduced
      interleukin-8 in sputum (311.94 ng/L to 122.02 ng/L; p = 0.027) were observed
      with patients given combined therapy. CONCLUSION: The study showed greater
      efficacy of long-term treatment with fenspiride and ipratropium bromide compared
      with ipratropium bromide alone in patients with CB. This combination regimen can
      be recommended for the reduction of inflammation and prevention of disease
      progression in patients with CB and may also be useful in patients with COB.

PMID- 17523777
TI  - Inadequate use of preventive strategies in patients receiving NSAIDs.
AB  - OBJECTIVE: Little is known about the factors that influence the decision to use
      NSAIDs in combination with gastroprotective drugs. The aims of this observational
      study were to evaluate the extent to which NSAID users are prescribed concomitant
      gastroprotective drug regimens ('preventive strategies'), and to determine how
      patient risk factors for NSAID-associated gastrointestinal toxicity and physician
      prescribing preferences influenced the decision to prescribe a gastroprotective
      drug in combination with an NSAID. DESIGN AND PATIENTS: The study was conducted
      on 29 June 2004 and comprised 109 eligible adult patients hospitalised at the
      Clinical Hospital Center, Zagreb. Use of NSAIDs and gastroprotective drugs, risk
      factors for NSAID-associated gastrointestinal toxicity, and physician prescribing
      preferences were monitored throughout the study. RESULTS: Sixty-six percent of
      patients receiving proton pump inhibitors or histamine H(2)-receptor antagonists
      with NSAIDs had no risk factors for gastrointestinal toxicity. Furthermore, 29%
      of patients who used NSAIDs had risk factors for gastrointestinal toxicity but
      were not receiving gastroprotective drugs. Even though patients at risk of NSAID
      associated gastrointestinal complications had higher odds of receiving preventive
      strategies (odds ratio 1.25), the absolute rate of utilisation of these therapies
      in at-risk populations was unacceptably low (69%). However, the strongest
      independent correlation for gastroprotective drug use was the prescribing
      physician, with an odds ratio of 6.40. CONCLUSION: This study demonstrates that
      an individual physician's prescribing style largely determines the odds of
      receiving preventive strategies with NSAID treatment and is more important than
      the patient's risk factors for gastrointestinal toxicity.

PMID- 17523778
TI  - Donepezil in vascular dementia : a neurosonological and neuropsychological study.

PMID- 17523779
TI  - Bilateral sensorineural hearing loss after adjuvant treatment with
      cyclophosphamide, methotrexate, Fluorouracil and alternative oral medications in
      a male with breast cancer.

PMID- 17523780
TI  - Generalised Dermatitis Induced by Pegylated Interferon-alpha-2b in a Patient
      Infected with Genotype-1 Hepatitis C Virus : Presentation of a Case.

PMID- 17523781
TI  - The rotational spectrum of CN-.
AB  - The rotational spectrum of the molecular negative ion CN(-) has been detected in
      the laboratory at high resolution. The four lowest transitions were observed in a
      low pressure glow discharge through C(2)N(2) and N(2). Conclusive evidence for
      the identification was provided by well-resolved nitrogen quadrupole hyperfine
      structure in the lowest rotational transition, and a measurable Doppler shift
      owing to ion drift in the positive column of the discharge. Three spectroscopic
      constants (B, D, and eQq) reproduce the observed spectrum to within one part in
      10(7) or better, allowing the entire rotational spectrum to be calculated well
      into the far IR to within 1 km s(-1) in equivalent radial velocity. CN(-) is an
      excellent candidate for astronomical detection, because the CN radical is
      observed in many galactic molecular sources, the electron binding energy of CN(-)
      is large, and calculations indicate CN(-) should be detectable in IRC+10216-the
      carbon star where C(6)H(-) has recently been observed. The fairly high
      concentration of CN(-) in the discharge implies that other molecular anions
      containing the nitrile group may be within reach.

PMID- 17523782
TI  - Theory of non-Condon emission from the interchain exciton in conjugated polymer
      aggregates.
AB  - The authors present here a simple analysis that explains the apparent
      strengthening of electron phonon interaction upon aggregation in conjugated
      polymer materials. The overall scheme is that of an intermolecular Herzberg
      Teller effect whereby sidebands of a forbidden transition are activated by
      oppositely phased vibrations. The authors show that upon aggregation, the 0-0
      emission becomes symmetry forbidden and the apparent redshift and remaining
      vibronic structure are due to sideband (0-1,0-2, etc.) emission. At higher
      temperatures, the 0-0 peak is due to thermal population in a higher lying even
      parity vibronic state rather than direct emission from the odd-paritied lowest
      intermolecular vibronic state.

PMID- 17523783
TI  - Probing thymine with laser ablation molecular beam Fourier transform microwave
      spectroscopy.
AB  - Laser ablation in combination with molecular beam Fourier transform microwave
      spectroscopy has been used to establish unambiguously the presence of the diketo
      form of thymine in the gas phase and to obtain its structure.

PMID- 17523784
TI  - Vapor-liquid coexistence in fluids of charged hard dumbbells.
AB  - Vapor-liquid coexistence in fluids of charged hard dumbbells, each made up of two
      oppositely charged hard spheres with diameters sigma and separation d, has been
      studied using grand-canonical Monte Carlo simulations. In the limit d/sigma-->0,
      and with the temperature scaled accordingly, the system corresponds to dipolar
      hard spheres. For separations in the range 0.3<d/sigma<or=1 the coexisting vapor
      phase contains compact clusters. For separations in the range 0.1<or=d/sigma<0.3
      the coexistence is between a chainlike vapor and a networklike liquid. Finite
      size effects preclude the simulation of the coexistence in systems with
      d/sigma<0.1, but extrapolations of the results to d/sigma-->0 yield estimates of
      the apparent critical parameters for dipolar hard spheres.

PMID- 17523785
TI  - Vibrational spectroscopy of hydrated electron clusters (H2O)(-)(15-50) via
      infrared multiple photon dissociation.
AB  - Infrared multiple photon dissociation spectra for size-selected water cluster
      anions (H2O)(n)(-), n=15-50, are presented covering the frequency range of 560
      1820 cm(-1). The cluster ions are trapped and cooled by collisions with ambient
      He gas at 20 K, with the goal of defining the cluster temperature better than in
      previous investigations of these species. Signal is seen in two frequency regions
      centered around 700 and 1500-1650 cm(-1), corresponding to water librational and
      bending motions, respectively. The bending feature associated with a double
      acceptor water molecule binding to the excess electron is clearly seen up to
      n=35, but above n=25; this feature begins to blueshift and broadens, suggesting a
      more delocalized electron binding motif for the larger clusters in which the
      excess electron interacts with multiple water molecules.

PMID- 17523786
TI  - Improved exchange-correlation potential for polarizability and dissociation in
      density functional theory.
AB  - The authors propose a novel approach to the problem of polarizabilities and
      dissociation in electric fields from the static limit of the Vignale-Kohn (VK)
      functional. The response to the purely scalar part of the VK response potential
      is considered. This potential has ground-state properties that notably improve
      over the full VK response density and over usual (semi-)local functionals. The
      correct qualitative behavior of our potentials means that it is expected to work
      well for polarizabilities in cases such as the H(2) chain, and it will also
      correctly dissociate open-shell fragments in a field.

PMID- 17523787
TI  - On the relationship between densities of Shannon entropy and Fisher information
      for atoms and molecules.
AB  - An analytical relationship between the densities of the Shannon entropy and
      Fisher information for atomic and molecular systems has been established in this
      work. Two equivalent forms of the Fisher information density are introduced as
      well. It is found that for electron densities of atoms and molecules the Shannon
      entropy density is intrinsically related to the electron density and the two
      forms of the Fisher information density. The formulas have been confirmed by the
      numerical results for the first two-row atoms.

PMID- 17523788
TI  - First hyperpolarizability of polymethineimine with long-range corrected
      functionals.
AB  - Using the long-range corrected (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 the longitudinal dipole moments and static electronic first
      hyperpolarizabilities of increasingly long polymehtineimine oligomers. For
      comparison purposes Hartree-Fock (HF), Moller-Plesset perturbation theory (MP2),
      and conventional pure and hybrid functionals have been considered as well. HF,
      generalized gradient approximation (GGA), and conventional hybrids provide too
      large dipole moments for long oligomers, while LC-DFT allows to reduce the
      discrepancy with respect to MP2 by a factor of 3. For the first
      hyperpolarizability, the incorrect evolution with the chain length predicted by
      HF is strongly worsened by BLYP, Perdew-Burke-Ernzerhof (PBE), and also by B3LYP
      and PBE0. On the reverse, LC-BLYP and LC-PBE hyperpolarizabilities are correctly
      predicted to be positive (but for the two smallest chains). Indeed, for medium
      and long oligomers LC hyperpolarizabilities are slightly smaller than MP2
      hyperpolarizabilities, as it should be. CAM-B3LYP also strongly improves the
      B3LYP results, though a bit less impressively for small chain lengths. The
      present study demonstrates the efficiency of long-range DFT, even in very
      pathological cases.

PMID- 17523789
TI  - Development of exchange-correlation functionals with minimal many-electron self
      interaction error.
AB  - New exchange-correlation functionals that address the important issue of many
      electron self-interaction are developed. This is carried out by considering the
      performance of the functional on systems with fractional numbers of electrons at
      the same time as more standard thermochemical tests. The inclusion of Coulomb
      attenuated exchange in the functional is facilitated by use of the adiabatic
      connection coupled with a short-range and long-range splittings. The new
      functionals have a good performance on thermochemistry and a much improved
      description of the total energy versus number of electrons and henceforth a much
      smaller many-electron self-interaction error.

PMID- 17523790
TI  - Ferroelectric phase transitions near ionic liquid/vacuum interfaces.
AB  - A simple theoretical model is developed describing ionic liquids as regular
      solutions. The separation of these ionic mixtures is studied on the base of the
      Cahn-Hilliard theory coupled with electrostatics. It is shown that the ionic
      liquids decompose to thin layers of oppositely charged liquids at low
      temperatures. At larger temperatures the separation occurs only near the ionic
      liquid/vacuum surface, thus explaining the oscillatory-decaying structure of the
      electric double layer observed via computer simulations. In contrast to
      noncharged liquids the ionic ones exhibit two critical temperatures, where the
      temperature coefficients of all characteristic lengths possess singularities.
      These second order ferroelectric phase transitions are possible explanations of
      the experimentally measured via light scattering peculiar temperature dependence
      of the interfacial dipole moment density on several ionic liquid/vacuum
      interfaces.

PMID- 17523791
TI  - Crystallization at the glass transition in supercooled thin films of methanol.
AB  - The stability of an amorphous material depends on how fast and by what mechanism
      crystallization occurs. Based on crystallization rate measurements through
      optical reflectivity changes in supercooled methanol thin films, it is observed
      for the first time that there is a definitive and detectable change of the
      crystallization mechanism at the glass transition temperature T(g). For methanol
      glasses below T(g)=103.4 K, crystallization occurs as an interface controlled,
      one-dimension process at frozen-in embryo sites, while in the deep supercooled
      liquid phase above T(g) crystallization is diffusion controlled in two dimensions
      with a constant nucleation rate and an activation energy of 107.8(+/-4.7) kJ/mol.

PMID- 17523792
TI  - Three-body symmetry-adapted perturbation theory based on Kohn-Sham description of
      the monomers.
AB  - An implementation of three-body symmetry-adapted perturbation theory (SAPT) of
      intermolecular interactions based on Kohn-Sham (KS) description of monomers with
      dispersion and induction nonadditive energies obtained from KS frequency
      dependent density susceptibilities [SAPT(DFT)] is presented. Using the density
      fitting approach, the nonadditive dispersion energy can be obtained with O(N(5))
      scaling with respect to the system size, the best scaling among all available
      methods of evaluating this quantity. Numerical results are reported for the
      helium, argon, water, and benzene trimers. The nonadditive energy computed for
      these systems is in a good agreement with benchmarks. Some hybrid perturbational
      supermolecular approaches are proposed that can provide--with only O(N(5))
      scaling--nonadditive energies with accuracy comparable to more expensive
      supermolecular methods, such as the third-order Moller-Plesset perturbation
      theory. Such approaches can be used for studying nonadditive effects in systems
      larger than it is currently possible with supermolecular methods at a level high
      enough to capture all essential components of the three-body interaction energy.

PMID- 17523793
TI  - Assessment of density functional theory optimized basis sets for gradient
      corrected functionals to transition metal systems: the case of small Nin (n<or=5)
      clusters.
AB  - Density functional calculations have been performed for small nickel clusters,
      Ni(n), Ni(n) (+), and Ni(n)(-) (n<or=5), using the linear combination of Gaussian
      type orbital density functional theory approach. Newly developed nickel all
      electron basis sets optimized for generalized gradient approximation (GGA) as
      well as an all-electron basis set optimized for the local density approximation
      were employed. For both neutral and charged systems, several isomers and
      different multiplicities were studied in order to determine the lowest energy
      structures. A vibrational analysis was performed in order to characterize these
      isomers. Structural parameters, harmonic frequencies, binding energies,
      ionization potentials, and electron affinities are reported. This work shows that
      the employed GGA basis sets for the nickel atom are important for the correct
      prediction of the ground state structures of small nickel clusters and that the
      structural assignment of these systems can be performed, with a good resolution,
      over the ionization potential.

PMID- 17523794
TI  - Monte Carlo method for computing density of states and quench probability of
      potential energy and enthalpy landscapes.
AB  - The thermodynamics and kinetics of a many-body system can be described in terms
      of a potential energy landscape in multidimensional configuration space. The
      partition function of such a landscape can be written in terms of a density of
      states, which can be computed using a variety of Monte Carlo techniques. In this
      paper, a new self-consistent Monte Carlo method for computing density of states
      is described that uses importance sampling and a multiplicative update factor to
      achieve rapid convergence. The technique is then applied to compute the
      equilibrium quench probability of the various inherent structures (minima) in the
      landscape. The quench probability depends on both the potential energy of the
      inherent structure and the volume of its corresponding basin in configuration
      space. Finally, the methodology is extended to the isothermal-isobaric ensemble
      in order to compute inherent structure quench probabilities in an enthalpy
      landscape.

PMID- 17523795
TI  - On the convergence improvement in the metadynamics simulations: a Wang-Landau
      recursion approach.
AB  - As a popular tool in exploring free energy landscapes, the metadynamics method
      has been widely applied to elucidate various chemical or biochemical processes.
      As deeply discussed by Laio et al. [J. Phys. Chem. B 109, 6714 (2005)], the size
      of the updating Gaussian function is pivotal to the free energy convergence
      toward the target free energy surface. For instance, a greater Gaussian height
      can facilitate the quick visit of a conformation region of interest; however, it
      may lead to a larger error of the calculated free energy surface. In contrast, a
      lower Gaussian height can guarantee a better resolution of the calculated free
      energy surface; however, it will take longer time for such a simulation to
      navigate through the defined conformational region. In order to reconcile such
      confliction, the authors present a method by implementing the Wang-Landau
      recursion scheme in the metadynamics simulations to adaptively update the height
      of the unit Gaussian function. As demonstrated in their model studies on both a
      toy system, and a realistic molecular system treated with the hybrid quantum
      mechanical and molecular mechanical (QMMM) potential, the present approach can
      quickly result in more decently converged free energy surfaces, compared with the
      classical metadynamics simulations employing the fixed Gaussian heights.

PMID- 17523796
TI  - A study of H+H2 and several H-bonded molecules by phaseless auxiliary-field
      quantum Monte Carlo with plane wave and Gaussian basis sets.
AB  - The authors present phaseless auxiliary-field (AF) quantum Monte Carlo (QMC)
      calculations of the ground states of some hydrogen-bonded systems. These systems
      were selected to test and benchmark different aspects of the new phaseless AF QMC
      method. They include the transition state of H+H(2) near the equilibrium geometry
      and in the van der Walls limit, as well as the H(2)O, OH, and H(2)O(2) molecules.
      Most of these systems present significant challenges for traditional independent
      particle electronic structure approaches, and many also have exact results
      available. The phaseless AF QMC method is used either with a plane wave basis
      with pseudopotentials or with all-electron Gaussian basis sets. For some systems,
      calculations are done with both to compare and characterize the performance of AF
      QMC under different basis sets and different Hubbard-Stratonovich decompositions.
      Excellent results are obtained using as input single Slater determinant wave
      functions taken from independent-particle calculations. Comparisons of the
      Gaussian based AF QMC results with exact full configuration interaction show that
      the errors from controlling the phase problem with the phaseless approximation
      are small. At the large basis-size limit, the AF QMC results using both types of
      basis sets are in good agreement with each other and with experimental values.

PMID- 17523797
TI  - Low-cost evaluation of the exchange Fock matrix from Cholesky and density fitting
      representations of the electron repulsion integrals.
AB  - The authors propose a new algorithm, "local K" (LK), for fast evaluation of the
      exchange Fock matrix in case the Cholesky decomposition of the electron repulsion
      integrals is used. The novelty lies in the fact that rigorous upper bounds to the
      contribution from each occupied orbital to the exchange Fock matrix are employed.
      By formulating these inequalities in terms of localized orbitals, the scaling of
      computing the exchange Fock matrix is reduced from quartic to quadratic with only
      negligible prescreening overhead and strict error control. Compared to the
      unscreened Cholesky algorithm, the computational saving is substantial for
      systems of medium and large sizes. By virtue of its general formulation, the LK
      algorithm can be used also within the class of methods that employ auxiliary
      basis set expansions for representing the electron repulsion integrals.

PMID- 17523798
TI  - Ab initio study of spectroscopic constants and anharmonic force field of 74GeCl2.
AB  - The equilibrium structure, spectroscopy constants, and anharmonic force field of
      germanium dichloride have been calculated at MP2, B3LYP, and CCSD(T) levels of
      theory employing two basis sets, cc-pVDZ and cc-pVTZ, respectively. The computed
      geometries, rotational constants, and vibration-rotation interaction constants,
      and quartic centrifugal distortion constants are compared with the available
      experimental data. The harmonic frequencies, anharmonic constants, and cubic and
      quartic force constants are predicted. The calculated results show that the MP2
      results are in excellent agreement with experiment and represent a substantial
      improvement over the results obtained from B3LYP. The CCSD(T) method is also an
      advisable choice to study anharmonic force field of molecules.

PMID- 17523799
TI  - Infrared spectroscopy of Cu+(H2O)(n) and Ag+(H2O)(n): coordination and solvation
      of noble-metal ions.
AB  - M(+)(H(2)O)(n) and M(+)(H(2)O)(n)Ar ions (M=Cu and Ag) are studied for exploring
      coordination and solvation structures of noble-metal ions. These species are
      produced in a laser-vaporization cluster source and probed with infrared (IR)
      photodissociation spectroscopy in the OH-stretch region using a triple quadrupole
      mass spectrometer. Density functional theory calculations are also carried out
      for analyzing the experimental IR spectra. Partially resolved rotational
      structure observed in the spectrum of Ag(+)(H(2)O)(1) x Ar indicates that the
      complex is quasilinear in an Ar-Ag(+)-O configuration with the H atoms
      symmetrically displaced off axis. The spectra of the Ar-tagged M(+)(H(2)O)(2) are
      consistent with twofold coordination with a linear O-M(+)-O arrangement for these
      ions, which is stabilized by the s-d hybridization in M(+). Hydrogen bonding
      between H(2)O molecules is absent in Ag(+)(H(2)O)(3) x Ar but detected in
      Cu(+)(H(2)O)(3) x Ar through characteristic changes in the position and intensity
      of the OH-stretch transitions. The third H(2)O attaches directly to Ag(+) in a
      tricoordinated form, while it occupies a hydrogen-bonding site in the second
      shell of the dicoordinated Cu(+). The preference of the tricoordination is
      attributable to the inefficient 5s-4d hybridization in Ag(+), in contrast to the
      extensive 4s-3d hybridization in Cu(+) which retains the dicoordination. This is
      most likely because the s-d energy gap of Ag(+) is much larger than that of
      Cu(+). The fourth H(2)O occupies the second shells of the tricoordinated Ag(+)
      and the dicoordinated Cu(+), as extensive hydrogen bonding is observed in
      M(+)(H(2)O)(4) x Ar. Interestingly, the Ag(+)(H(2)O)(4) x Ar ions adopt not only
      the tricoordinated form but also the dicoordinated forms, which are absent in
      Ag(+)(H(2)O)(3) x Ar but revived at n=4. Size dependent variations in the spectra
      of Cu(+)(H(2)O)(n) for n=5-7 provide evidence for the completion of the second
      shell at n=6, where the dicoordinated Cu(+)(H(2)O)(2) subunit is surrounded by
      four H(2)O molecules. The gas-phase coordination number of Cu(+) is 2 and the
      resulting linearly coordinated structure acts as the core of further solvation
      processes.

PMID- 17523800
TI  - A study on the stability of O2 on oxometalloporphyrins by the first principles
      calculations.
AB  - The authors investigated the interaction of oxometalloporphyrins (MO(por))-
      specifically, MoO(por), WO(por), TiO(por), VO(por), and CrO(por)--with O(2) by
      using first principles calculations. MoO(por) and WO(por) undergo reactions with
      O(2); on the other hand, TiO(por), VO(por), and CrO(por) do not. Next, they
      compared the interaction of MoO(por) and WO(por) with O(2). Activation barriers
      for the reactions of MoO(por) and WO(por) with a side-on O(2) are small. For
      MoO(por)(O(2)), the activation barrier for the reverse reaction that liberates
      O(2) is also small; however, that for WO(por)(O(2)) is large. The experimental
      results that photoirradiation with visible light or heating of Mo
      (VI)O(tmp)(O(2)) regenerates Mo (VI)O(tmp) by liberating O(2) while W
      (VI)O(tmp)(O(2)) does not [J. Tachibana, T. Imamura, and Y. Sasaki, Bull. Chem.
      Soc. Jpn. 71, 363 (1998)] are explained by the difference in activation barriers
      of the reverse reactions. This means that bonds formed between the W atom and
      O(2) are stronger than those between the Mo atom and O(2). The bond strengths can
      be explained by differences in the energy levels between the highest occupied
      molecular orbital of MoO(por) and WO(por), which are mainly formed from the a
      orbitals of the central metal atom and pi(*) orbitals of O(2).

PMID- 17523801
TI  - Theoretical investigation of the ground and low-lying excited states of nickel
      carbide, NiC.
AB  - The electronic structure and bonding of 19 states of the diatomic nickel carbide
      (NiC) has been studied by multireference methods. Potential energy curves have
      been constructed for all states, whereas for the three lowest states of
      symmetries X (1)Sigma(+), a (3)Pi, and A (1)Pi well separated from the rest of
      the states, special attention was paid through the use of very large basis sets
      and the calculation of core-valence correlation and scalar relativistic effects.
      The recommended binding energies for these states are 91, 67, and 54 kcal/mol
      with respect to the ground state atoms. Our results in general can be considered
      in fair agreement with the limited experimental findings.

PMID- 17523802
TI  - Dynamics on the HOCO potential energy surface studied by dissociative
      photodetachment of HOCO- and DOCO-.
AB  - An experimental study of the dissociative photodetachment (DPD) dynamics of HOCO(
      ) and DOCO(-) at a photon energy of 3.21 eV has been carried out to probe the
      potential energy surface of the HOCO free radical and the dynamics of the OH+CO-
      >H+CO(2) reaction. These photoelectron-photofragment coincidence experiments
      allow the identification of photodetachment processes leading to the production
      of stable HOCO free radicals and both the H+CO(2) and OH+CO dissociation channels
      on the neutral surface. Isotopic substitution by deuterium in the parent ion is
      observed to reduce the product branching ratio for the D+CO(2) channel,
      consistent with tunneling playing a role in this dissociation pathway. Other
      isotope effects on the detailed partitioning of kinetic energy between
      photoelectrons and photofragments are also discussed. The results are compared to
      recent theoretical predictions of this DPD process, and evidence for the
      involvement of vibrationally excited HOCO(-) anions is discussed.

PMID- 17523803
TI  - Compatibility between methanol and water in the three-dimensional cage formation
      of large-sized protonated methanol-water mixed clusters.
AB  - Infrared spectra of large-sized protonated methanol-water mixed clusters,
      H(+)(MeOH)(m)(H(2)O)(n) (m=1-4, n=4-22), were measured in the OH stretch region.
      The free OH stretch bands of the water moiety converged to a single peak due to
      the three-coordinated sites at the sizes of m+n=21, which is the magic number of
      the protonated water cluster. This is a spectroscopic signature for the formation
      of the three-dimensional cage structure in the mixed cluster, and it demonstrates
      the compatibility of a small number of methanol molecules with water in the
      hydrogen-bonded cage formation. Density functional theory calculations were
      carried out to examine the relative stability and structures of selected isomers
      of the mixed clusters. The calculation results supported the microscopic
      compatibility of methanol and water in the hydrogen-bonded cage development. The
      authors also found that in the magic number clusters, the surface protonated
      sites are energetically favored over their internal counterparts and the excess
      proton prefers to take the form of H(3)O(+) despite the fact that the proton
      affinity of methanol is greater than that of water.

PMID- 17523804
TI  - Hydrogen-bonded OH stretching modes of methanol clusters: a combined IR and Raman
      isotopomer study.
AB  - A comprehensive study of the OH and OD stretching fundamentals in clusters of
      methanol and its isotopomers CH(3)OD, CD(3)OH, and CD(3)OD provides detailed
      insights into the hydrogen-bond mediated coupling as a function of cluster size.
      The combination of infrared and Raman supersonic jet spectroscopy enables the
      observation and assignment of all hydrogen-bonded OH stretching modes of isolated
      methanol trimer and methanol tetramer. A consistent explanation for the spectral
      complexity observed more than a decade ago in methanol trimer in terms of low
      frequency methyl umbrella motions is provided. Previous explanations based on
      cluster isomerism or anharmonic resonances are ruled out by dedicated jet
      experiments. The first experimental lower bound for concerted quadruple proton
      transfer in S(4) symmetric methanol tetramer is derived and compared with
      theoretical predictions. The observed isotope effects offer insights into the
      anharmonicity of the localized OH bond. The performance of harmonic B3LYP and MP2
      calculations in predicting hydrogen-bond-induced spectral shifts and couplings is
      investigated.

PMID- 17523805
TI  - Effect of alkyl substituents on excited state intramolecular proton transfer
      dynamics of jet-cooled bis(benzoxazolyl)phenoles.
AB  - Structural factors affecting the dynamics of the excited state intramolecular
      proton transfer (ESIPT) are studied for alkyl derivatives of 2,5-bis(2
      benzoxazolyl)phenol. Two fluorescence bands with equal decay times are observed
      in solution, while only one--emitted by the phototautomer--in supersonic jet. All
      evidence indicates the existence of a potential barrier in the S(1) state. Upon
      deuteration of the OH group the laser induced fluorescence (LIF) excitation
      spectra become much sharper as a result of slowing down the proton transfer
      reaction. Two conformers (rotamers) of each compound in the ground state were
      detected using hole burning technique. With a help of theoretical calculations
      three vibrations were identified as the most active ones in reducing the distance
      between two heavy atoms, N and O, involved in H-bond formation. The widths of
      (0,0) transitions in LIF excitation spectra decrease with increasing size or
      number of alkyl substituents at terminal aromatic rings. The corresponding
      calculated rate constants of ESIPT reaction ( approximately 10(12) s(-1))
      decrease approximately three times upon the substituent effect. In contrast,
      model compound 2,5-bis(2-benzoxazolyl)-4-methoxyphenol (BBMP) with OCH(3)
      parasubstituent in central ring slows down the ESIPT reaction to such an extent
      that double, primary and phototautomeric, fluorescences coexist.

PMID- 17523806
TI  - Spin-orbit coupling in O2(v)+O2 collisions. II. Quantum scattering calculations
      on dimer states involving the X 3 Sigma g -, a 1 Delta g, and b 1 Sigma g +
      states of O2.
AB  - The dynamics of collisional deactivation of O(2)(X (3)Sigma(g) (-),v=20-32) by
      O(2)(X (3)Sigma(g) (-),v(')=0) is investigated in detail by means of quantum
      mechanical calculations. The theoretical approach involves ab initio potential
      energy surfaces correlating to the X (3)Sigma(g) (-), a (1)Delta(g), and b
      (1)Sigma(g) (+) states of O(2) and their corresponding spin-orbit couplings [F.
      Dayou, M. I. Hernandez, J. Campos-Martinez, and R. Hernandez-Lamoneda, J. Chem.
      Phys. 123, 074311 (2005)]. Accurate Rydberg-Klein-Rees potentials are included in
      order to improve the description of the vibrational structure of the fragments.
      The calculated Boltzmann-averaged depletion probabilities display a dependence
      with v in good agreement with experimental measurements. The onset of the
      vibrational-to-electronic (V-E) depletion mechanism is noticeable for v>/=26, and
      it is due to energy transfer to both a (1)Delta(g) and b (1)Sigma(g) (+) states
      of the diatom. For O(2)(X (3)Sigma(g) (-),v=28), a further and sharp increase in
      the removal probabilities is caused by a near degeneracy with the O(2)(b
      (1)Sigma(g) (+),v=19) vibrational state. Analysis of the temperature dependence
      of the Boltzmann-averaged probabilities indicates a transition from the
      vibrational-to-translational to the V-E energy transfer regime, which can be
      traced back to the behavior of the inelastic probabilities as functions of
      kinetic energy. Furthermore, branching ratios for outcomes through the three
      different electronic states show a strong propensity towards populating a unique
      vibrational level within each electronic state. These results provide supported
      evidence that spin-orbit couplings account for a large portion of the "dark
      channel" reported in total depletion measurements. New insight for further
      experimental and theoretical investigations is also given.

PMID- 17523807
TI  - Reaction dynamics following electron capture of chlorofluorocarbon adsorbed on
      water cluster: a direct density functional theory molecular dynamics study.
AB  - The electron capture dynamics of halocarbon and its water complex have been
      investigated by means of the full dimensional direct density functional theory
      molecular dynamics method in order to shed light on the mechanism of electron
      capture of a halocarbon adsorbed on the ice surface. The CF(2)Cl(2) molecule and
      a cyclic water trimer (H(2)O)(3) were used as halocarbon and water cluster,
      respectively. The dynamics calculation of CF(2)Cl(2) showed that both C-Cl bonds
      are largely elongated after the electron capture, while one of the Cl atoms is
      dissociated from CF(2)Cl(2) (-) as a Cl(-) ion. Almost all total available energy
      was transferred into the internal modes of the parent CF(2)Cl radical on the
      product state, while the relative translational energy of Cl(-) was significantly
      low due to the elongation of two C-Cl bonds. In the case of a halocarbon-water
      cluster system, the geometry optimization of neutral complex CF(2)Cl(2)(H(2)O)(3)
      showed that one of the Cl atoms interacts with n orbital of water molecules of
      trimer and the other Cl atom existed as a dangling Cl atom. After the electron
      capture, only one C-Cl bond (dangling Cl atom) was rapidly elongated, whereas the
      other C-Cl bond is silent during the reaction. The dangling Cl atom was directly
      dissociated from CF(2)Cl(2) (-)(H(2)O)(3) as Cl(-). The fast Cl(-) ion was
      generated from CF(2)Cl(2) (-)(H(2)O)(3) on the water cluster. The mechanism of
      the electron capture of halocarbon on water ice was discussed on the basis of the
      theoretical results.

PMID- 17523808
TI  - Electronic spectrum of UO2(2+) and [UO2Cl4]2- calculated with time-dependent
      density functional theory.
AB  - The electronic spectra of UO(2) (2+) and [UO(2)Cl(4)](2-) are calculated with a
      recently proposed relativistic time-dependent density functional theory method
      based on the two-component zeroth-order regular approximation for the inclusion
      of spin-orbit coupling and a noncollinear exchange-correlation functional. All
      excitations out of the bonding sigma(u) (+) orbital into the nonbonding delta(u)
      or phi(u) orbitals for UO(2) (2+) and the corresponding excitations for
      [UO(2)Cl(4)](2-) are considered. Scalar relativistic vertical excitation energies
      are compared to values from previous calculations with the CASPT2 method. Two
      component adiabatic excitation energies, U-O equilibrium distances, and symmetric
      stretching frequencies are compared to CASPT2 and combined configuration
      interaction and spin-orbit coupling results, as well as to experimental data. The
      composition of the excited states in terms of the spin-orbit free states is
      analyzed. The results point to a significant effect of the chlorine ligands on
      the electronic spectrum, thereby confirming the CASPT2 results: The excitation
      energies are shifted and a different luminescent state is found.

PMID- 17523809
TI  - Relativistic corrections to the non-Born-Oppenheimer energies of the lowest
      singlet Rydberg states of 3He and 4He.
AB  - In this work the authors present an approach to calculate the leading-order
      relativistic corrections for ground and excited states of helium isotopomers. In
      the calculations they used variational wave functions expanded in terms of
      explicitly correlated Gaussians obtained without assuming the Born-Oppenheimer
      approximation.

PMID- 17523810
TI  - A full analytic potential energy curve for the a 3 Sigma+ state of KLi from a
      limited vibrational data set.
AB  - Fourier transform spectra of near-infrared laser-induced fluorescence in
      (39)K(6)Li show transitions to high vibrational levels of both the X (1)Sigma(+)
      and a (3)Sigma(+) electronic states. These include 147 transitions into six
      vibrational levels of the a (3)Sigma(+) state, which lie between 7 and 88 cm(-1)
      below the dissociation asymptote. Unfortunately, their energies span less than
      30% of the well depth. However, fitting those data to eigenvalues of analytical
      model potential functions whose outer limbs incorporate the theoretically
      predicted long-range form, V(R) approximately D-C(6)R(6)-C(8)R(8), yields
      complete, plausible potential curves for this state. The best fits converge to
      remarkably similar solutions which indicate that D(e)=287(+/-4) cm(-1) and
      R(e)=4.99(+/-0.09) A for the a (3)Sigma(+) state of KLi, with omega(e)=47.3(+/
      1.4) and 44.2(+/-1.5) cm(-1) for (39)K(6)Li and (39)K(7)Li, respectively.
      Properties of the resulting potential are similar to those of a published ab
      initio potential and are consistent with those of the analogous states of Li(2),
      K(2), Na(2), and NaK.

PMID- 17523811
TI  - The 39K(2) 2(3)Sigma(g)+ state: observation and analysis.
AB  - The (39)K(2) 2 (3)Sigma(g) (+) state has been observed by perturbation
      facilitated infrared-infrared double resonance spectroscopy and two-photon
      excitation. Resolved fluorescence spectra into the a (3)Sigma(u) (+) state have
      been recorded. The observed vibrational levels have been assigned as the v=23-25,
      27, 28, 31-33, 38-45, 47, and 53 levels by comparing the observed and calculated
      spectra of the 2 (3)Sigma(g) (+)-->a (3)Sigma(u) (+) transitions. Molecular
      constants have been obtained using a global fitting procedure with a
      comprehensive set of experimental data. Fine and hyperfine splittings have been
      resolved in the excitation spectra. Perturbations between the 2 (3)Sigma(g) (+)
      and 2 (3)Pi(g) states were observed. The hyperfine patterns of the 2 (3)Sigma(g)
      (+) levels are strongly affected by the perturbation. The perturbation-free and
      weakly perturbed levels follow the case b(betaS) coupling scheme, while the
      perturbed levels follow case b(beta J) coupling. A Fermi contact constant,
      b(F)=65+/-10 MHz, has been obtained. Intensity anomalies of rotational lines
      appeared both in the 2 (3)Sigma(g) (+) approximately 2 (3)Pi(g)<--b (3)Pi(u)
      excitation spectra and in the 2 (3)Sigma(g) (+) approximately 2 (3)Pi(g)-->a
      (3)Sigma(u) (+) resolved fluorescence spectra. These intensity anomalies can be
      explained in terms of a quantum-mechanical interference effect.

PMID- 17523812
TI  - Formation, detection, and stability studies of neutral vanadium sulfide clusters.
AB  - Neutral vanadium sulfide clusters are generated by the reaction of seeded
      hydrogen sulfide in a helium carrier gas with laser ablated vanadium metal within
      a supersonic nozzle. The exiting clusters are expanded into a vacuum in a
      molecular beam and are ionized by both ultraviolet (UV) and vacuum UV (VUV) laser
      radiation. The generated ions are detected by a time of flight mass spectrometer.
      With single photon ionization (SPI) employing VUV (118 nm) radiation, sulfur rich
      clusters (V(m)S(n), n>m+1) and hydrogen containing clusters (V(m)S(n)H(x), x>0)
      are observed. With multiphoton ionization (MPI) through nanosecond UV (193 nm)
      radiation, these sulfur rich and hydrogen containing clusters cannot be observed,
      indicating severe fragmentation generated by MPI and the importance of SPI in
      determining the neutral vanadium sulfide cluster distribution. With MPI through
      femtosecond UV (226 nm) radiation, a few sulfur rich and hydrogen containing
      clusters are detected, but most clusters observed by SPI are still undetected
      even by femtosecond MPI. Density functional theory calculations are applied to
      optimize energies and structures of the clusters with m=1-3 and n=0-7. The
      experimental results are well interpreted based on the calculations. The
      calculated and experimental results for vanadium sulfides are compared with those
      of vanadium oxides in literature.

PMID- 17523813
TI  - Anisotropic bulletlike emission of terminal ethynyl fragment ions: ionization of
      ethynylbenzene-d under intense femtosecond laser fields.
AB  - The authors investigated Coulomb explosions of ethynylbenzenes under intense
      femtosecond laser fields. Deuteration on the edge of the triple bond gave
      information about specific fragment emissions and the contribution of hydrogen
      migration. Some fragments not resulting from migration were emitted in the
      direction of laser polarization. These were ethynyl fragment ions (D(+), CD(+),
      C(2)D(+), and C(3)D(+)). Although two bonds have to be cleaved to produce
      C(3)D(+), the rigid character of the triple bond was maintained in the Coulomb
      explosion process. In contrast, fragment ions, which are formed after single or
      double hydrogen migration, showed isotropic emissions with distinct kinetic
      energies. The character of the substituents has been found to hold even under
      strong laser light fields where violent fragmentation took place. The ethynyl
      parts were emitted like bullets from the molecular frame of ethynylbenzene
      despite the explosion into pieces of the main body of benzene ring.

PMID- 17523814
TI  - Electron collisions with furan.
AB  - The authors report integral, differential and momentum transfer cross sections
      for elastic scattering of low-energy electrons by C(4)H(4)O (furan) molecules.
      Their calculations employed the Schwinger multichannel method with
      pseudopotentials and were performed in the static-exchange and in the static
      exchange plus polarization approximations. The authors found two shape resonances
      located around 2.1 and 4.2 eV that belong to the B(1) and A(2) symmetries of the
      C(2v) group, respectively. The authors' results are consistent with recent
      measurements of vertical electron attachment energies.

PMID- 17523815
TI  - Slice imaging of the quantum state-to-state cross section for photodissociation
      of state-selected rovibrational bending states of OCS (v2=0,1,2/JlM)+hnu-
      >CO(J)+S(1D2).
AB  - Using hexapole quantum state-selection of OCS (v(2)=0,1,2/JlM) and high
      resolution slice imaging of quantum state-selected CO(J), the state-to-state
      cross section OCS (v(2)=0,1,2/JlM)+hnu-->CO(J)+S((1)D(2)) was measured for
      bending states up to v(2)=2. The population density of the state-selected OCS
      (v(2)=0,1,2 /JlM) in the molecular beam was obtained by resonantly enhanced
      multiphoton ionization of OCS and comparison with room temperature bulk gas. A
      strong increase of the cross section with increasing bending state is observed
      for CO(J) in the high J region, J=60-67. Integrating over all J states the
      authors find sigma(v(2)=0):sigma(v(2)=1):sigma(v(2)=2)=1.0:7.0:15.0. A
      quantitative comparison is made with the dependence of the transition dipole
      moment function on the bending angle.

PMID- 17523816
TI  - Molecular nitrogen-N2 properties: the intermolecular potential and the equation
      of state.
AB  - Quantum mechanical (QM) high precision calculations were used to determine N(2)
      N(2) intermolecular interaction potential. Using QM numerical data the
      anisotropic potential energy surface was obtained for all orientations of the
      pair of the nitrogen molecules in the rotation invariant form. The new N(2)-N(2)
      potential is in reasonably good agreement with the scaled potential obtained by
      van der Avoird et al. using the results of Hartree-Fock calculations [J. Chem.
      Phys. 84, 1629 (1986)]. The molecular dynamics (MD) of the N(2) molecules has
      been used to determine nitrogen equation of state. The classical motion of N(2)
      molecules was integrated in rigid rotor approximation, i.e., it accounted only
      translational and rotational degrees of freedom. Fincham [Mol. Simul. 11, 79
      (1993)] algorithm was shown to be superior in terms of precision and energy
      stability to other algorithms, including Singer [Mol. Phys. 33, 1757 (1977)],
      fifth order predictor-corrector, or Runge-Kutta, and was therefore used in the MD
      modeling of the nitrogen pressure [S. Krukowski and P. Strak, J. Chem. Phys. 124,
      134501 (2006)]. Nitrogen equation of state at pressures up to 30 GPa (300 kbars)
      and temperatures from the room temperature to 2000 K was obtained using MD
      simulation results. Results of MD simulations are in very good agreement (the
      error below 1%) with the experimental data on nitrogen equation of state at
      pressures below 1 GPa (10 kbars) for temperatures below 1800 K [R. T. Jacobsen et
      al., J. Phys. Chem. Ref. Data 15, 735 (1986)]. For higher temperatures, the
      deviation is slightly larger, about 2.5% which still is a very good agreement.
      The slightly larger difference may be attributed to the vibrational motion not
      accounted explicitly by rigid rotor approximation, which may be especially
      important at high temperatures. These results allow to obtain reliable equation
      of state of nitrogen for pressures up to 30 GPa (300 kbars), i.e., close to
      molecular nitrogen stability limit, determined by Nellis et al. [Phys. Rev. Lett.
      53, 1661 (1984)].

PMID- 17523817
TI  - Ab initio melting curve of molybdenum by the phase coexistence method.
AB  - Ab initio calculations of the melting curve of molybdenum for the pressure range
      0-400 GPa are reported. The calculations employ density functional theory (DFT)
      with the Perdew-Burke-Ernzerhof exchange-correlation functional in the projector
      augmented wave (PAW) implementation. Tests are presented showing that these
      techniques accurately reproduce experimental data on low-temperature body
      centered cubic (bcc) Mo, and that PAW agrees closely with results from the full
      potential linearized augmented plane-wave implementation. The work attempts to
      overcome the uncertainties inherent in earlier DFT calculations of the melting
      curve of Mo, by using the "reference coexistence" technique to determine the
      melting curve. In this technique, an empirical reference model (here, the
      embedded-atom model) is accurately fitted to DFT molecular dynamics data on the
      liquid and the high-temperature solid, the melting curve of the reference model
      is determined by simulations of coexisting solid and liquid, and the ab initio
      melting curve is obtained by applying free-energy corrections. The calculated
      melting curve agrees well with experiment at ambient pressure and is consistent
      with shock data at high pressure, but does not agree with the high-pressure
      melting curve deduced from static compression experiments. Calculated results for
      the radial distribution function show that the short-range atomic order of the
      liquid is very similar to that of the high-T solid, with a slight decrease of
      coordination number on passing from solid to liquid. The electronic densities of
      states in the two phases show only small differences. The results do not support
      a recent theory according to which very low dT(m)dP values are expected for bcc
      transition metals because of electron redistribution between s-p and d states.

PMID- 17523818
TI  - Direct measurement of the effective charge in nonpolar suspensions by optical
      tracking of single particles.
AB  - The authors develop an ultrasensitive method for the measurement of the charge
      carried by a colloidal particle in a nonpolar suspension. The technique uses the
      phenomenon of the resonance of a particle held in an optical tweezer trap and
      driven by a sinusoidal electric field. The trapped particle forms a strongly
      damped harmonic oscillator whose fluctuations are a function of gamma, the ratio
      of the root-mean-square average of the electric and thermal forces on the
      particle. At low applied fields (gamma<<1) the particle is confined to the
      optical axis, while at high fields (gamma>>1) the probability distribution of the
      particle is double peaked. The periodically modulated thermal fluctuations are
      measured with nanometer sensitivity using an interferometric position detector.
      Charges, as low as a few elementary charges, can be measured with an uncertainty
      of about 0.25 e. This is significantly better than previous techniques and opens
      up new possibilities for the study of nonpolar suspensions.

PMID- 17523819
TI  - Interface dynamics of microscopic cavities in water.
AB  - An analytical description of the interface motion of a collapsing nanometer-sized
      spherical cavity in water is presented by a modification of the Rayleigh-Plesset
      equation in conjunction with explicit solvent molecular dynamics simulations.
      Quantitative agreement is found between the two approaches for the time-dependent
      cavity radius R(t) at different solvent conditions while in the continuum picture
      the solvent viscosity has to be corrected for curvature effects. The typical
      magnitude of the interface or collapse velocity is found to be given by the ratio
      of interfacial tension and solvent viscosity, v approximately gamma/eta, while
      the curvature correction accelerates collapse dynamics on length scales below the
      equilibrium crossover scales ( approximately 1 nm) of hydrophobic solvation. The
      study offers a starting point for an efficient implicit modeling of water
      dynamics in aqueous nanoassembly and protein systems in nonequilibrium.

PMID- 17523820
TI  - Resonance Raman and density functional theory investigation of the
      photodissociation dynamics of the A-band absorption of (E)-beta-nitrostyrene in
      cyclohexane solution.
AB  - Resonance Raman spectra were obtained for (E)-beta-nitrostyrene in cyclohexane
      solution with excitation wavelengths in resonance with the charge transfer (CT)
      band absorption spectrum. These spectra indicate that the Franck-Condon region
      photodissociation dynamics have multidimensional character with motion
      predominantly along the nominal NO(2) symmetric stretch mode (nu(14)), the
      nominal C=C stretch mode (nu(8)), the nominal benzene ring stretch mode (nu(9)),
      accompanied by a smaller amount of motion along the nominal ONO symmetric
      bend/benzene ring stretch mode (nu(34)), the nominal CCH in-plane bending mode
      (nu(20)), the nominal HC=CH in-plane bending mode (nu(18)), the nominal NO(2)
      asymmetric stretch mode (nu(11)), the nominal C-N stretch/benzene ring breathing
      mode (nu(27)), and the nominal CCC trigonal bending mode (nu(25)). A preliminary
      resonance Raman intensity analysis was done and these results for (E)-beta
      nitrostyrene were compared to results previously reported for several
      nitrobenzene and trans-stilbene compounds. The differences and similarities
      between the CT-band resonance Raman spectra and vibrational reorganizational
      energies for (E)-beta-nitrostyrene relative to those for nitrobenzene and trans
      stilbene were briefly discussed.

PMID- 17523821
TI  - The dielectric virial expansion and the models of dipolar hard-sphere fluid.
AB  - The virial expansion technique to determine the dielectric constant epsilon of
      dipolar hard-sphere fluid is developed. It is shown that the formalism allows to
      bring into agreement the results of Debye's, Onsager's, and Langevin's to the
      problem. The third virial coefficient of epsilon is considered as a series over
      dipolar parameter lambda=m(2)d(3)kT. The terms up to O(lambda(11)) are calculated
      analytically providing a correct description of the third virial coefficient for
      small and intermediate values of lambda (0<or=lambda<or=4). The results of the
      dielectric virial series are compared with the Monte Carlo data for epsilon found
      by Matyushov and Ladanyi [J. Chem. Phys. 110, 994 (1999)]. The theory is in
      agreement with simulations only at small values of lambda<or=2. At higher
      polarities, the virial series diverges. Realization of the renormalization
      procedure permits to enlarge the range of applicability of the virial series. In
      this way, the new expression for the dielectric constant as a function of two
      dipolar parameters, lambda and y=4 pi nm(2)9kT, has been found explicitly. The
      expression gives a perfect upper bound of the dielectric constant and is more
      reliable for determination of epsilon than the previously known ones.

PMID- 17523822
TI  - Comparison of proton conduction in KTaO3 and SrZrO3.
AB  - In the present paper, the authors focus on proton conduction pathways in a cubic
      perovskite KTaO(3) and an orthorhombic perovskite SrZrO(3). Density functional
      theory with a generalized gradient approximation is used to find proton binding
      sites. The nudged elastic band method is used to find transition states between
      minima. With this potential energy map of binding and transition states,
      adjacency matrices and their analogs identify four types of conduction paths in
      KTaO(3). Distortions from these paths are seen in SrZrO(3). In both cases, the
      lowest energy path has an intraoctahedral transfer rate-limiting barrier. A
      Fourier analysis of the OH stretch in ab initio molecular dynamics simulations
      revealed a strongly redshifted OH stretch in SrZrO(3) relative to KTaO(3). Hence,
      an orthorhombic system with a lowest energy conduction path limited by an
      intraoctahedral barrier can exhibit a redshifted OH stretch.

PMID- 17523823
TI  - Absorption and scattering of light by Pt, Pd, Ag, and Au nanodisks: absolute
      cross sections and branching ratios.
AB  - Localized surface plasmons (LSPs) of metallic nanoparticles decay either
      radiatively or via an electron-hole pair cascade. In this work, the authors have
      experimentally and theoretically explored the branching ratio of the radiative
      and nonradiative LSP decay channels for nanodisks of Ag, Au, Pt, and Pd, with
      diameters D ranging from 38 to 530 nm and height h=20 nm, supported on a fused
      silica substrate. The branching ratio for the two plasmon decay channels was
      obtained by measuring the absorption and scattering cross sections as a function
      of photon energy. The former was obtained from measured extinction and scattering
      coefficients, using an integrating sphere detector combined with particle density
      measurements obtained from scanning electron microscopy images of the
      nanoparticles. Partly angle-resolved measurements of the scattered light allowed
      the authors to clearly identify contributions from dipolar and higher plasmonic
      modes to the extinction, scattering, and absorption cross sections. Based on
      these experiments they find that absorption dominates the total scattering cross
      section in all the examined cases for small metallic nanodisks (D<100 nm). For
      D>100 nm absorption still dominates for Pt and Pd nanodisks, while scattering
      dominates for Au and Ag. A theoretical approach, where the metal disks are
      approximated as oblate spheroids, is used to account for the trends in the
      measured cross sections. The field problem is solved in the electrostatic limit.
      The spheroid is treated as an induced dipole for which the dipolar polarizability
      is calculated based on spheroid geometry and the (bulk) dielectric response
      function of the metal the spheroid consists of and the dielectric medium
      surrounding it. One might expect this model to be inappropriate for disks with
      D>100 nm since effects due to the retardation of the incoming field across the
      metallic nanodisk and contributions from higher plasmonic modes are neglected.
      However, this model describes quite well the energy dependence of the dipolar
      resonance, the full width at half maximum, and the total extinction cross section
      for all four metallic systems, even when 100<D<500 nm, indicating that the
      combined contribution of the effects not included in the model is small for the
      systems studied. For this reason the authors have extended the use of the same
      model to study scattering/absorption branching ratios. The main conclusions
      include the following. (i) Both the magnitude and peak position in extinction
      cross section are well accounted for by the model. (ii) The branching ratio for
      radiative and nonradiative decay is reasonably well accounted for. (iii) The
      model fails to account for the correct magnitudes of the measured absorption and
      scattering cross sections for larger particles in the case of Ag and Au. Possible
      reasons for this discrepancy are discussed.

PMID- 17523824
TI  - Ion transport and selectivity in nanopores with spatially inhomogeneous fixed
      charge distributions.
AB  - Polymeric nanopores with fixed charges show ionic selectivity when immersed in
      aqueous electrolyte solutions. The understanding of the electrical interaction
      between these charges and the mobile ions confined in the inside nanopore
      solution is the key issue in the design of potential applications. The authors
      have theoretically described the effects that spatially inhomogeneous fixed
      charge distributions exert on the ionic transport and selectivity properties of
      the nanopore. A comprehensive set of one-dimensional distributions including the
      skin, core, cluster, and asymmetric cases are analyzed on the basis of the Nernst
      Planck equations. Current-voltage curves, nanopore potentials, and transport
      numbers are calculated for the above distributions and compared with those
      obtained for a homogeneously charged nanopore with the same average fixed charge
      concentration. The authors have discussed if an appropriate design of the spatial
      fixed charge inhomogeneity can lead to an enhancement of the transport and
      selectivity with respect to the homogeneous nanopore case. Finally, they have
      compared the theoretical predictions with relevant experimental data.

PMID- 17523825
TI  - Nonlocal optical effects on the fluorescence and decay rates for admolecules at a
      metallic nanoparticle.
AB  - A phenomenological model is implemented to study the decay rates of fluorescing
      molecules in the vicinity of a metallic nanoparticle, wherein the nonlocal
      optical response of the particle is accounted for via the hydrodynamic model for
      the description of the free electrons in the metal. These nonlocal effects are
      examined for each of the radiative rate and the nonradiative rate of the
      admolecule, respectively. In addition, the overall fluorescence rate which
      includes the enhancement ratio for the driving field intensity is also studied.
      It is found that for particles of very small sizes (<10 nm), the nonlocal
      effects, in general, lead to significantly greater fluorescence rates and smaller
      nonradiative decay rates for the admolecules, with the effects on radiative rates
      depending crucially on the orientation of the molecules. Furthermore, the effects
      are mostly noticeable for molecules close to the metal particle and in processes
      where higher multipolar interactions are significant such as those in
      nonradiative decay processes. Above all, these nonlocal effects can still be
      observable in the presence of large surface damping imposed on the metallic
      electrons due to the ultrasmall sizes of these nanoparticles. The relevance of
      these effects to some of the latest experiments is discussed.

PMID- 17523826
TI  - Exciton energy transfer between optically forbidden states of molecular
      aggregates.
AB  - 3-ethyl-2-[3-(3-ethyl-2(3H)-benzoxazolylidene)-1-propenyl]benzoxazolium iodide
      (dye I) and pseudoisocyanine bromide are employed to form H aggregates as donors
      and J aggregates as acceptors. The energy of an H band of the H aggregates is
      higher than that of a J band of the J aggregates. It was confirmed that
      excitation of the H band does not emit fluorescence by comparison of excitation
      spectra of dye I H aggregates with that of dye I monomer. Absorption,
      fluorescence, and excitation spectra of spin-coated films of H aggregates mixed
      with various quantities of J aggregates have been observed. Excitation spectra
      probed at the J band are found to have a component of the H band. Fluorescence
      spectra originated from excitation of the H band are extracted and qualitatively
      analyzed. It is confirmed that excitation of the H band causes to emit
      fluorescence of a J band of the J aggregates. These phenomena show that exciton
      energy can transfer from the lowest energy in electronic states of the H
      aggregate, which state is optically forbidden, to electronic state of the J
      aggregate.

PMID- 17523827
TI  - Trends in C-O and C-N bond formations over transition metal surfaces: an insight
      into kinetic sensitivity in catalytic reactions.
AB  - Transition metal catalyzed bond formation is a fundamental process in catalysis
      and is of general interest throughout chemistry. To date, however, the knowledge
      of association reactions is rather limited, relative to what is known about
      dissociative processes. For example, surprisingly little is known about how the
      bond-forming ability of a metal, in general, varies across the Periodic Table. In
      particular, the effect of reactant valency on such trends is poorly understood.
      Herein, the authors examine these key issues by using density functional theory
      calculations to study CO and CN formations over the 4d metals. The calculations
      reveal that the chemistries differ in a fundamental way. In the case of CO
      formation, the reaction enthalpies span a much greater range than those of CN
      formation. Moreover, CO formation is found to be kinetically sensitive to the
      metal; here the reaction barriers (E(a)) are found to be influenced by the
      reaction enthalpy. CN formation, conversely, is found to be relatively
      kinetically insensitive to the metal, and there is no correlation found between
      the reaction barriers and the reaction enthalpy. Analysis has shown that at the
      final adsorbed state, the interaction between N and the surface is relatively
      greater than that of O. Furthermore, in comparison with O, relatively less
      bonding between the surface and N is observed to be lost during transition state
      formation. These greater interactions between N and the surface, which can be
      related to the larger valency of N, are found to be responsible for the
      relatively smaller enthalpy range and limited variation in E(a) for CN formation.

PMID- 17523828
TI  - Adsorption of linear alkanes on Cu(111): temperature and chain-length dependence
      of the softened vibrational mode.
AB  - The vibrational spectra of linear alkanes, with lengths ranging from n-propane to
      n-octane, were examined on a copper surface by reflection-absorption infrared
      spectroscopy. The appearance and frequency of the "soft mode," a feature
      routinely seen in studies of saturated hydrocarbons adsorbed on metals, were
      examined and compared between the different adsorbates. The frequency of the mode
      was found to be dependent on both the number of methylene units of each alkane as
      well as specific aspects of the order of the monolayer phase. Studies of
      monolayer coverages at different temperatures provide insights into the nature of
      the two-dimensional (2D) melting transitions of these adlayer structures, ones
      that can be inferred from observed shifts in the soft vibrational modes appearing
      in the C-H stretching region of the infrared spectrum. These studies support
      recently reported hypotheses as to the origins of such soft modes: the metal
      hydrogen interactions that mediate them and the dynamics that underlay their
      pronounced temperature dependencies. The present data strongly support a model
      for the 2D to one-dimensional order-order phase transition arising via a
      continuous rather than discrete first-order process.

PMID- 17523829
TI  - Calculation of the mean first passage time tested on simple two-dimensional
      models.
AB  - A particle diffusing in a two-dimensional (2D) container, shaped as a simplified
      configuration space of two passing 2D circular particles in a flat channel, is
      considered. The mean first passage time through one absorbing boundary is
      calculated using the one-dimensional Fick-Jacobs equation and its modification;
      both derived by mapping the 2D diffusion equation onto the longitudinal
      ("reaction") coordinate. The obtained results are compared with the hopping time,
      defined as the inverted lowest eigenvalue of the full 2D problem. The comparison
      shows that the mapped equations give reliable results, in contrast to predictions
      of the simplest concept of the transition state theory.

PMID- 17523830
TI  - Diffusion in tight confinement: a lattice-gas cellular automaton approach. I.
      Structural equilibrium properties.
AB  - The thermodynamic and transport properties of diffusing species in microporous
      materials are strongly influenced by their interactions with the confining
      framework, which provide the energy landscape for the transport process. The
      simple topology and the cellular nature of the alpha cages of a ZK4 zeolite
      suggest that it is appropriate to apply to the study of the problem of diffusion
      in tight confinement a time-space discrete model such as a lattice-gas cellular
      automaton (LGCA). In this paper we investigate the properties of an equilibrium
      LGCA constituted by a constant number of noninteracting identical particles,
      distributed among a fixed number of identical cells arranged in a three
      dimensional cubic network and performing a synchronous random walk at constant
      temperature. Each cell of this network is characterized by a finite number of two
      types of adsorption sites: the exit sites available to particle transfer and the
      inner sites not available to such transfers. We represent the particle-framework
      interactions by assuming a differentiation in binding energy of the two types of
      sites. This leads to a strong dependence of equilibrium and transport properties
      on loading and temperature. The evolution rule of our LGCA model is constituted
      by two operations (randomization, in which the number of particles which will be
      able to try a jump to neighboring cells is determined, and propagation, in which
      the allowed jumps are performed), each one applied synchronously to all of the
      cells. The authors study the equilibrium distribution of states and the
      adsorption isotherm of the model under various conditions of loading and
      temperature. In connection with the differentiation in energy between exit and
      inner sites, the adsorption isotherm is described by a conventional Langmuir
      isotherm at high temperature and by a dual-site Langmuir isotherm at low
      temperature, while a first order diffuse phase transition takes place at very low
      temperature.

PMID- 17523831
TI  - Diffusion in tight confinement: a lattice-gas cellular automaton approach. II.
      Transport properties.
AB  - In this second paper the authors study the transport properties of the lattice
      gas cellular automaton presented in Paper I [J. Chem. Phys. 126, 194709 (2007)]
      to model adsorption and dynamics of particles in a lattice of confining cells.
      Their work shows how a surprisingly simple parallel rule applied to a static
      network of cells joined by links set in space and time can generate a wide range
      of dynamical behaviors. In their model the cells are the elementary constituent
      objects of the network. They are a portion of space structured in sites which are
      energetically different. Each cell can accommodate a given maximum number of
      particles, and each pair of neighboring cells can exchange at most one particle
      at a time. The predictions of the model are in qualitative agreement with both
      experimental observations and molecular dynamics simulation results.

PMID- 17523832
TI  - Generalized Chudley-Elliott vibration-jump model in activated atom surface
      diffusion.
AB  - Here the authors provide a generalized Chudley-Elliott expression for the
      activated atom surface diffusion which takes into account the coupling between
      both low-frequency vibrational motion (namely, the frustrated translational
      modes) and diffusion. This expression is derived within the Gaussian
      approximation framework for the intermediate scattering function at low coverage.
      Moreover, inelastic contributions (arising from creation and annihilation
      processes) to the full width at half maximum of the quasielastic peak are also
      obtained.

PMID- 17523833
TI  - Geometry and electronic structure of impurity-trapped excitons in Cs2GeF6:U4+
      crystals. The 5f17s1 manifold.
AB  - Excitons trapped at impurity centers in highly ionic crystals were first
      described by McClure and Pedrini [Phys. Rev. B 32, 8465 (1985)] as excited states
      consisting of a bound electron-hole pair with the hole localized on the impurity
      and the electron on nearby lattice sites, and a very short impurity-ligand bond
      length. In this work the authors present a detailed microscopic characterization
      of impurity-trapped excitons in U(4+)-doped Cs(2)GeF(6). Their electronic
      structure has been studied by means of relativistic ab initio model potential
      embedded cluster calculations on (UF(6))(2-) and (UF(6)Cs(8))(6+) clusters
      embedded in Cs(2)GeF(6), in combination with correlation methods based on
      multireference wave functions. The local geometry of the impurity-trapped
      excitons, their potential energy curves, and their multielectronic wave functions
      have been obtained as direct, nonempirical results of the methods. The calculated
      excited states appear to be significantly delocalized outside the UF(6) volume
      and their U-F bond length turns out to be very short, closer to that of a
      pentavalent uranium defect than to that of a tetravalent uranium defect. The wave
      functions of these excited states show a dominant U 5f(1)7s(1) configuration
      character. This result has never been anticipated by simpler models and reveals
      the unprecedented ability of diffuse orbitals of f-element impurities to act as
      electron traps in ionic crystals.

PMID- 17523834
TI  - Columnar versus smectic order in systems of charged colloidal rods.
AB  - We study the stability of inhomogeneous liquid crystalline states in systems of
      monodisperse, stiff, charged rods. By means of a bifurcation analysis applied to
      the Onsager free energy for charged rods in strongly nematic states, we
      investigate nematic-smectic and nematic-columnar instabilities as a function of
      the Debye screening length kappa(-1). While the nematic-smectic transition
      clearly preempts the nematic-columnar one in the regime of strong screening
      (i.e., small kappa(-1)) a marked stability of hexagonal columnar order is
      observed at larger screening lengths. The theoretical results are substantiated
      by Brownian dynamics computer simulation results based on the Yukawa site model.
      Our findings connect to experiments on tobacco mosaic virus rods, in particular,
      but might be relevant for soft rodlike mesogens in strong external directional
      fields in general.

PMID- 17523835
TI  - Phase diagram of Gaussian-core nematics.
AB  - The authors study a simple model of a nematic liquid crystal made of parallel
      ellipsoidal particles interacting via a repulsive Gaussian law. After identifying
      the relevant solid phases of the system through a careful zero-temperature
      scrutiny of as many as eleven candidate crystal structures, they determine the
      melting temperature for various pressure values, also with the help of exact free
      energy calculations. Among the prominent features of this model are pressure
      driven reentrant melting and the stabilization of a columnar phase for
      intermediate temperatures.

PMID- 17523836
TI  - Self-assembly of patchy particles into polymer chains: a parameter-free
      comparison between Wertheim theory and Monte Carlo simulation.
AB  - The authors numerically study a simple fluid composed of particles having a hard
      core repulsion, complemented by two short-ranged attractive (sticky) spots at the
      particle poles, which provides a simple model for equilibrium polymerization of
      linear chains. The simplicity of the model allows for a close comparison, with no
      fitting parameters, between simulations and theoretical predictions based on the
      Wertheim perturbation theory. This comparison offers a unique framework for the
      analytic prediction of the properties of self-assembling particle systems in
      terms of molecular parameters and liquid state correlation functions. The
      Wertheim theory has not been previously subjected to stringent tests against
      simulation data for ordering across the polymerization transition. The authors
      numerically determine many of the thermodynamic properties governing this basic
      form of self-assembly (energy per particle, order parameter or average fraction
      of particles in the associated state, average chain length, chain length
      distribution, average end-to-end distance of the chains, and the static structure
      factor) and find that predictions of the Wertheim theory accord remarkably well
      with the simulation results.

PMID- 17523837
TI  - Correlations between designability and various structural characteristics of
      protein lattice models.
AB  - Using six kinds of lattice types (4 x 4, 5 x 5, and 6 x 6 square lattices; 3 x 3
      x 3 cubic lattice; and 2+3+4+3+2 and 4+5+6+5+4 triangular lattices), three
      different size alphabets (HP, HNUP, and 20 letters), and two energy functions,
      the designability of protein structures is calculated based on random samplings
      of structures and common biased sampling (CBS) of protein sequence space. Then
      three quantities stability (average energy gap), foldability, and partnum of the
      structure, which are defined to elucidate the designability, are calculated. The
      authors find that whatever the type of lattice, alphabet size, and energy
      function used, there will be an emergence of highly designable (preferred)
      structure. For all cases considered, the local interactions reduce degeneracy and
      make the designability higher. The designability is sensitive to the lattice
      type, alphabet size, energy function, and sampling method of the sequence space.
      Compared with the random sampling method, both the CBS and the Metropolis Monte
      Carlo sampling methods make the designability higher. The correlation
      coefficients between the designability, stability, and foldability are mostly
      larger than 0.5, which demonstrate that they have strong correlation
      relationship. But the correlation relationship between the designability and the
      partnum is not so strong because the partnum is independent of the energy. The
      results are useful in practical use of the designability principle, such as to
      predict the protein tertiary structure.

PMID- 17523839
TI  - Gas-solid coexistence of adhesive spheres.

PMID- 17523838
TI  - GBr6NL: a generalized Born method for accurately reproducing solvation energy of
      the nonlinear Poisson-Boltzmann equation.
AB  - The nonlinear Poisson-Boltzmann (NLPB) equation can provide accurate modeling of
      electrostatic effects for nucleic acids and highly charged proteins. Generalized
      Born methods have been developed to mimic the linearized Poisson-Boltzmann (LPB)
      equation at substantially reduced cost. The computer time for solving the NLPB
      equation is approximately fivefold longer than for the LPB equation, thus
      presenting an even greater obstacle. Here we present the first generalized Born
      method, GBr(6)NL, for mimicking the NLPB equation. GBr(6)NL is adapted from
      GBr(6), a generalized Born method recently developed to reproduce the solvation
      energy of the LPB equation [Tjong and Zhou, J. Phys. Chem. B 111, 3055 (2007)].
      Salt effects predicted by GBr(6)NL on 55 proteins overall deviate from NLPB
      counterparts by 0.5 kcal/mol from ionic strengths from 10 to 1000 mM, which is
      approximately 10% of the average magnitudes of the salt effects. GBr(6)NL
      predictions for the salts effects on the electrostatic interaction energies of
      two protein:RNA complexes are very promising.

PMID- 17523841
TI  - Selection bias in cancer risk estimation from A-bomb survivors.
AB  - We consider the possible bias in cancer risk estimation from A-bomb survivors due
      to selection of the cohort by survival. The paper considers both relevant
      information from the data and basic theoretical issues involved. The most direct
      information from the data comes from making various restrictions on the dose
      distance range, partly to reduce differential selection and partly just to reduce
      the magnitude of the selection. These analyses suggest that there are no serious
      biases, but they are not conclusive. Theoretical considerations include laying
      out more explicitly than usual just how biases could result from the selection.
      This involves heterogeneities in the ability to survive acute effects, in
      baseline and radiogenic cancer rates, and most importantly the correlation
      between survival-related and cancer-related heterogeneities. Following on this,
      idealized modeling is used to quantify the extent of possible bias in terms of
      the assumed values of the magnitude of these heterogeneities and their
      correlation. It is indicated that these values would need to be very large to
      introduce substantial bias. Based on all these considerations, it seems unlikely
      that the bias in cancer risk estimation could be large in relation to other
      uncertainties in generalizing from what is seen among A-bomb survivors; in
      particular, indications are that the bias in relative risks is unlikely to be as
      large as 0.05 to 0.07. For solid cancer this would correspond to bias in the
      excess relative risk at 1 Sv of at most about 15-20%.

PMID- 17523842
TI  - The greater lethality of UVB radiation to cultured human cells is associated with
      the specific activation of a DNA damage-independent signaling pathway.
AB  - UV radiation causes cell death through the activation of various intracellular
      signaling molecules in both DNA damage-dependent and -independent manners. The
      ability of middle-wavelength UV (UVB) radiation to form DNA photoproducts is less
      than that of short-wavelength UV (UVC) radiation; however, the differences
      between UVB and UVC radiation in the extent of DNA damage-independent signaling
      and its contribution to cell death have not been well characterized. When cells
      were irradiated with UVB or UVC radiation at doses that generated equivalent
      amounts of DNA photoproducts, UVB radiation induced more clonogenic cell death,
      apoptotic cells, mitochondrial cytochrome C release, and intracellular oxidative
      stress. Among the signaling molecules examined, levels of p53 phosphorylated at
      Ser-392 and p38 were higher in UVB-irradiated cells than in UVC-irradiated cells.
      Both phosphorylations were reduced by treating cells with an antioxidant.
      Furthermore, an inhibitor of p38 also blocked the phosphorylation of p53 at Ser
      392. These results suggest that UVB radiation activates the p38 pathway through
      the generation of oxidative stress, which merges with the DNA p53 pathway by
      phosphorylation of p53 at ser392. This greater contribution of the DNA damage
      independent pathway in UVB-irradiated cells may explain the greater lethality of
      UVB radiation.

PMID- 17523843
TI  - Proteasomes and proteasome activator 200 kDa (PA200) accumulate on chromatin in
      response to ionizing radiation.
AB  - Proteasome activator 200 kDa (PA200) forms nuclear foci after exposure of cells
      to ionizing radiation and enhances proteasome activity in vitro. Within cells, it
      is unclear whether PA200 responds to radiation alone or in association with
      proteasomes. In the present study, we identified three forms of cellular PA200
      (termed PA200i, ii and iii) at the mRNA and protein levels. Neither PA200ii nor
      PA200iii appears to associate with proteasomes. All detectable PA200i is
      associated with proteasomes, which indicates that PA200i and proteasomes function
      together within the cell. Consistent with this idea, we find that exposure of
      cells to radiation leads to an equivalent accumulation of both PA200i and core
      proteasomes on chromatin. This increase in PA200 and proteasomes on chromatin is
      not specific to the stage of cell cycle arrest since it occurs in cells that
      arrest in G(2)/M and cells that arrest in G(1)/S after exposure to radiation.
      These data provide evidence that PA200 and proteasomes function together within
      cells and respond to a specific radiation-induced damage independent of the stage
      of cell cycle arrest.

PMID- 17523844
TI  - Chromosome aberrations do not persist in the lymphocytes or bone marrow cells of
      mice irradiated in utero or soon after birth.
AB  - Mice were exposed at various ages to 1 Gy or 2 Gy of X rays, and translocation
      frequencies in peripheral blood T cells, spleen cells, and bone marrow cells were
      determined with FISH painting of chromosomes 1 and 3 when the animals were 20
      weeks old. It was found that the mean translocation frequencies were very low (<
      or =0.8%) in mice exposed in the fetal or early postnatal stages. However, with
      the increase in animal age at the time of irradiation, the frequency observed at
      20 weeks old became progressively higher then reached a plateau (about 5%) when
      mice were irradiated when > or =6 weeks old. A major role of p53 (Trp53)
      dependent apoptosis for elimination of aberrant cells was not suggested because
      irradiated fetuses, regardless of the p53 gene status, showed low translocation
      frequencies (1.8% in p53(-/-) mice and 1.4% in p53(+/-) mice) compared to the
      frequency in the p53(-/-) mother (7.4%). In contrast, various types of
      aberrations were seen in spleen and liver cells when neonates were examined
      shortly after irradiation, similar to what was observed in bone marrow cells
      after irradiation in adults. We interpreted the results as indicating that fetal
      cells are generally sensitive to induction of chromosome aberrations but that the
      aberrant cells do not persist because fetal stem cells tend to be free of
      aberrations and their progeny replace the pre-existing cell populations during
      the postnatal growth of the animals.

PMID- 17523845
TI  - Effect of treatment schedule on the interaction of Cisplatin and radiation in
      human lung cancer cells.
AB  - This study was designed to determine the effects of the treatment schedule on the
      interaction between cisplatin and radiation. Cells of a human squamous cell lung
      cancer cell line were treated with cisplatin and radiation using three treatment
      protocols: 1-h exposure to cisplatin immediately followed by irradiation (A), 4
      day continuous exposure to cisplatin immediately followed by irradiation (B), and
      1-h exposure to cisplatin followed by irradiation after a 4-day interval (C). The
      interactions were assessed by isobologram, cell cycle distribution and apoptosis.
      The combination resulted in a additive effect in every protocol. Cell cycle
      accumulation at G(2)/M phase before irradiation was observed in Protocols B and
      C, whereas no cell cycle shift in the limited time course was noted in Protocol
      A. Although a 4-day continuous exposure to cisplatin and a 1-h exposure to
      cisplatin followed by a 4-day interval before irradiation caused significantly
      increased apoptosis, an additional increase in apoptosis after irradiation was
      not observed in Protocols B and C, whereas Protocol A showed an additional
      increase. Despite a cell cycle shift favoring radiation sensitivity, the drug
      radiation interactions in Protocols B and C were additive, possibly because of
      negative effects including induction of a durable G(2)/M-phase arrest and
      suppression of apoptosis by cisplatin.

PMID- 17523846
TI  - Adaptive response for chromosomal inversions in pKZ1 mouse prostate induced by
      low doses of X radiation delivered after a high dose.
AB  - Adaptive responses are induced by stress such as X radiation and result in a
      lower than expected biological response. Two-dose adaptive response experiments
      typically involve a low priming dose followed by a subsequent high radiation
      dose. Here, we used a sensitive in vivo chromosomal inversion assay to
      demonstrate for the first time an adaptive response when a low dose (0.01-1 mGy)
      was given several hours after a high 1000-mGy radiation dose. The adaptive
      responses in this study were of similar magnitude to the two-dose adaptive
      responses previously observed in this test system when the low dose was given
      first. A chromosomal inversion adaptive response was also induced by two 1000-mGy
      doses and when a 1-mGy dose was preceded or followed by a dose of 0.01 mGy, but
      not by two 4000-mGy doses. This is also the first example of an adaptive response
      when both doses are low. Our data agree with previous reports of an on-off
      mechanism of adaptive response. The induction of an adaptive response by a low
      dose after a high damaging dose provides evidence that the mechanisms underlying
      radiation adaptive responses are not due to prevention of damage induced by the
      high dose but to modulation of the cellular response to this damage.

PMID- 17523847
TI  - Radiobiological characterization of human tumor cell multilayers after
      conventional and particle irradiation.
AB  - The goal of this study was to establish planar multilayers from human tumor cells
      (WiDr and SiHa) as a model for irradiation of solid tumors. In addition to using
      conventional X rays (250 kV) as a reference standard, multilayers were tested for
      their suitability in cell survival studies with heavy-ion irradiation ((12)C(6+))
      in the plateau and the extended Bragg peak with a scanned ion beam. Multilayers
      of both cell lines showed decreased survival compared to the corresponding
      monolayers after both X and heavy-ion irradiation. This multicellular
      sensitization effect is in contrast to the multicellular resistance or contact
      effect commonly described in the literature. Flow cytometry measurements showed
      an arrest of irradiated SiHa cells in G(2)/M phase. In contrast to the transient
      arrest of the monolayers, the multilayers stayed in a prolonged arrest. After
      Bragg-peak irradiation of monolayers, the arrest time was increased by 12-24 h,
      and more cells were arrested than with X rays. For multilayers, there were no
      differences between G(2) arrest after X rays and heavy ions for the entire
      observation period.

PMID- 17523848
TI  - Bystander effects of bioreductive drugs: potential for exploiting pathological
      tumor hypoxia with dinitrobenzamide mustards.
AB  - Tumor hypoxia is an important therapeutic target, and it can potentially be
      exploited by hypoxia-activated prodrugs. However, physiological hypoxia in normal
      tissues is a limitation. One solution would be to confine activation to severely
      (pathologically) hypoxic tissue, using hypoxia-activated prodrugs that provide a
      bystander effect through diffusion of the activated cytotoxin to adjacent regions
      at intermediate oxygen concentrations (associated with partial radioresistance).
      To evaluate this requirement, we identified five hypoxia-activated prodrugs with
      at least 10-fold higher potency against a cell line (A549-P540(puro))
      overexpressing human cytochrome P450 reductase (P450R) relative to A549-Lo21
      cells with 200-fold lower P450R activity. Bystander killing by these hypoxia
      activated prodrugs was tested in anoxic multicellular layer co-cultures of these
      two cell lines. Cytotoxic potency against A549-Lo21 cells was unaffected by the
      presence of A549-P450(puro) cells for tirapazamine and RSU-1069 but increased
      more than 10-fold for the aziridinyldintrobenzamide CB 1954, more than 14-fold
      for the corresponding nitrogen mustard SN 23862, and 15-fold for its water
      soluble analog SN 23816. The cytotoxic extracellular metabolites resulting from
      hypoxic nitroreduction of CB 1954 and SN 23862 by A549-P450(puro) cells were
      identified by LC/MS and bioassay methods. For SN 23862, these included the 2
      amine metabolite, previously, identified as the bystander metabolite from aerobic
      activation by the E. coli nfsB nitroreductase, but also novel di-reduced
      metabolites. Cytotoxicity of SN 23862 to A549-P450(puro) cells was inhibited by
      lower concentrations of oxygen than for tirapazamine. The combination of
      selective activation under severe hypoxia with an efficient bystander effect
      identifies the dinitrobenzamide mustards for further development as hypoxia
      activated prodrugs.

PMID- 17523849
TI  - p53 (TRP53) deficiency-mediated antiapoptosis escape after 5 Gy X irradiation
      still induces stem cell leukemia in C3H/He mice: comparison between whole-body
      assay and bone marrow transplantation (BMT) assay.
AB  - Mice exposed to a lethal dose of radiation were repopulated with heterozygous
      p53(+/-) (TRP53(+/-)) bone marrow cells and then exposed to doses of 1, 3 and 5
      Gy 1 month later. This resulted in the transplanted bone marrow-specific diseases
      other than competitively induced nonhematopoietic neoplasms. Interestingly, the
      present study showed a high frequency of stem cell leukemia, i.e., leukemias
      characterized by a lack of differentiation due also to p53 deficiency, even after
      5 Gy irradiation. The frequencies of stem cell leukemias (and those of total
      hematopoietic malignancies) were 16% (24%) at 1 Gy and 45% (75%) at 3 Gy.
      Furthermore, markedly high incidences of stem cell leukemias were observed at 5
      Gy in p53(+/-) mice, i.e., 87% (100%) in the transplantation assay and 60%
      (83.3%) in the whole-body assay, whereas a conventional whole-body assay induced
      only 14% in wild-type mice. The high incidence of stem cell leukemias observed in
      this study using heterozygous p53-deficient mice agrees with results of a
      previous study of homozygous p53-deficient mice and is consistent with the high
      frequency of loss of heterozygosity in the p53 wild-type allele observed in
      leukemias. This suggests that the target cells for radiation-induced stem cell
      leukemias may be p53-deficient hematopoietic stem cells.

PMID- 17523850
TI  - Transmission of genomic instability from a single irradiated human chromosome to
      the progeny of unirradiated cells.
AB  - Ionizing radiation can induce chromosome instability that is transmitted over
      many generations after irradiation in the progeny of surviving cells, but it
      remains unclear why this instability can be transmitted to the progeny. To
      acquire knowledge about the transmissible nature of genomic instability, we
      transferred an irradiated human chromosome into unirradiated mouse recipient
      cells by microcell fusion and examined the stability of the transferred human
      chromosome in the microcell hybrids. The transferred chromosome was stable in all
      six microcell hybrids in which an unirradiated human chromosome had been
      introduced. In contrast, the transferred chromosome was unstable in four out of
      five microcell hybrids in which an irradiated human chromosome had been
      introduced. The aberrations included changes in the irradiated chromosome itself
      and rearrangements with recipient mouse chromosomes. Thus the present study
      demonstrates that genomic instability can be transmitted to the progeny of
      unirradiated cells by a chromosome exposed to ionizing radiation, implying that
      the instability is caused by the irradiated chromosome itself and also that the
      instability is induced by the nontargeted effect of radiation.

PMID- 17523851
TI  - Cancer and noncancer mortality in populations living near uranium and vanadium
      mining and milling operations in Montrose County, Colorado, 1950-2000.
AB  - Mining and milling of uranium in Montrose County on the Western Slope of Colorado
      began in the early 1900s and continued until the early 1980s. To evaluate the
      possible impact of these activities on the health of communities living on the
      Colorado Plateau, mortality rates between 1950 and 2000 among Montrose County
      residents were compared to rates among residents in five similar counties in
      Colorado. Standardized mortality ratios (SMRs) were computed as the ratio of
      observed numbers of deaths in Montrose County to the expected numbers of deaths
      based on mortality rates in the general populations of Colorado and the United
      States. Relative risks (RRs) were computed as the ratio of the SMRs for Montrose
      County to the SMRs for the five comparison counties. Between 1950 and 2000, a
      total of 1,877 cancer deaths occurred in the population residing in Montrose
      County, compared with 1,903 expected based on general population rates for
      Colorado (SMR(CO) 0.99). There were 11,837 cancer deaths in the five comparison
      counties during the same 51-year period compared with 12,135 expected (SMR(CO)
      0.98). There was no difference between the total cancer mortality rates in
      Montrose County and those in the comparison counties (RR = 1.01; 95% CI 0.96
      1.06). Except for lung cancer among males (RR = 1.19; 95% CI 1.06-1.33), no
      statistically significant excesses were seen for any causes of death of a priori
      interest: cancers of the breast, kidney, liver, bone, or childhood cancer,
      leukemia, non-Hodgkin lymphoma, renal disease or nonmalignant respiratory
      disease. Lung cancer among females was decreased (RR = 0.83; 95% CI 0.67-1.02).
      The absence of elevated mortality rates of cancer in Montrose County over a
      period of 51 years suggests that the historical milling and mining operations did
      not adversely affect the health of Montrose County residents. Although
      descriptive correlation analyses such as this preclude definitive causal
      inferences, the increased lung cancer mortality seen among males but not females
      is most likely due to prior occupational exposure to radon and cigarette smoking
      among underground miners residing in Montrose County, consistent with previous
      cohort studies of Colorado miners and of residents of the town of Uravan in
      Montrose County.

PMID- 17523852
TI  - Retrospective biodosimetry among United States radiologic technologists.
AB  - Measurement of chromosome translocations in peripheral blood lymphocytes has been
      used to quantify prior exposure to ionizing radiation, including for workers
      exposed to low, chronic doses. We assessed translocation frequencies in a subset
      of U.S. radiologic technologists to substantiate ionizing radiation dose
      estimates developed for 110,418 technologists who worked between 1916 and 1984.
      From 3,441 cohort members known to have begun working before 1950, we selected a
      sample of 152, stratified by estimated cumulative dose, over-sampling from higher
      dose categories and excluding persons with a prior cancer diagnosis, a personal
      or family history of chromosomal instability disorders, or a current history of
      smoking. Estimates of film-badge dose ranged from less than 10 cSv to more than
      30 cSv. Blood samples, obtained in 2004, were analyzed by fluorescence in situ
      hybridization (FISH) whole chromosome painting by simultaneously labeling
      chromosomes 1, 2 and 4 in red and 3, 5 and 6 in green. Translocations were scored
      in 1800 well-spread metaphase cells and expressed per 100 cell equivalents (CE)
      per person. Linear Poisson regression models with allowance for overdispersion
      were used to assess the relationship between estimated occupational red bone
      marrow absorbed dose in cGy and translocation frequency, adjusted for age, gender
      and estimated red bone marrow absorbed dose score from personal diagnostic
      procedures. We observed 0.09 excess translocations per 100 CE per cGy red bone
      marrow dose (95% CI: -0.01, 0.2; P = 0.07), which is similar to the expected
      estimate based on previous cytogenetic studies (0.05 excess translocations per
      100 CE per cGy). Despite uncertainty in the estimates of occupational red bone
      marrow absorbed doses, we found good general agreement between the doses and
      translocation frequencies, lending support to the credibility of the dose
      assessment for this large cohort of U.S. radiologic technologists.

PMID- 17523853
TI  - Low-dose risk assessment.

PMID- 17523854
TI  - In memoriam: Edward L Gillette (1932-2006).

PMID- 17523855
TI  - A view from inside Arizona and New Mexico Indian country: pursuing a health
      career path.
AB  - INTRODUCTION: The stories of individuals working within the health system in
      Arizona and New Mexico Indian Country were examined to discover interests and
      needs related to their health career goals and advancement. The aims were: to
      identify what would be helpful to support educational and career progress; and to
      determine the barriers to advancement. METHODS: Community action research
      methodology was used. A semi-structured interview schedule administered by two of
      the investigators made up the qualitative interview portion of a two-part survey
      research design. This qualitative portion of the larger study is reported.
      Interviewees were chosen from health workers in Arizona and New Mexico Indian
      country who returned workplace-distributed questionnaires that indicated they
      were interested in career advancement. The interviewees were selected to be
      representative of the occupational background, work site, age, and cultural
      identity of those who returned the questionnaire. Investigators took notes by
      hand independently during interviews and reviewed both sets of notes
      simultaneously; the agreed on responses were entered as text data within 2 hours
      of the interviews. QRS Nudist software (QRS Software; Melbourne, VIC, Australia)
      was used to sort interview responses to each question in a successive fashion
      using a constant comparative method to identify key themes within and across
      questions. RESULTS: Twenty-five personal interviews were conducted in community
      locations convenient to the interviewee between February and April 2003. The
      duration of the interviews was 30 min and 60 min. Eighty percent of interviewees
      were American Indian and 80% percent were women. Themes within interviewees'
      stories regarding barriers to advancement included: 'making ends meet', dealing
      with the educational system, uncertainty and inflexibility in the current work
      setting, and not wanting to disadvantage children by their career decision.
      Themes related to what participants said they needed included 'making sure the
      bills are paid', making sure their children were not negatively affected by their
      decision to further their education, and being sure of the worth of further
      education in the workplace. Several across-interview themes included pursuing
      many sequential incremental educational and career steps, many interruptions and
      failed attempts at pursuing advanced education, and informal, verbal information
      gathering patterns when seeking career advancement information. CONCLUSION:
      Barriers to career advancement and education arise from multiple sources.
      Supporting career advancement of community-rooted health workers in Indian
      Country will require partnership and collaboration across the education, health
      services, and community sectors. Financial management supports, workplace
      policies designed to support career-oriented education, consistent and accurate
      information regarding the educational process, and making courses more accessible
      will be necessary to support these non-traditional students. Health professions
      schools should regard their community-based graduates as ambassadors and provide
      them with ongoing accurate information, because they will be sought after to
      provide information to others. Innovative programs to assist in loan
      consolidation and financial management are needed to allow native health workers
      to be able to provide for their families should they wish to advance their
      careers. Collaboration across disciplines and programs in the education sector to
      support a limited set of prerequisite courses would help eliminate unnecessary or
      redundant courses.

PMID- 17523856
TI  - The effects of communication skills training on pediatricians' and parents'
      communication during "sick child" visits.
AB  - This article reports the development and evaluation of a physician-parent
      communication skills training program designed to improve communication regarding
      antibiotic prescribing for children. Four pediatricians and 81 parents
      participated in the study, which involved audiotaping "sick child" office visits
      and then coding transcripts for evidence of program influence on information
      seeking, giving, and verifying, as well as relational communication. Parents who
      received training were more likely to verify information, t(79) = 1.82, p = .04,
      and more likely to express concerns, t(79) = 1.79, p = .04, than were parents who
      did not receive training; there was a nonsignificant trend for trained parents to
      be more likely to give information, t(79) = 1.7, p = .051. In terms of physician
      behavior, there were nonsignificant trends for physicians to spend more time
      creating a partnership with parents after training than before training, t(3) =
      2.29, p = .053, and to encourage more questions from parents after training than
      before, t(3) = 2.15, p = .06. In addition, once one outlier parent in the control
      condition was removed from the analysis, the results showed that physicians spent
      more time addressing treatment options after training than before, t(3) = 2.9, p
      = .03. The results of this study are considered promising, with effects shown for
      various important elements of physician-parent communication. Implications of
      results and directions for future research are discussed.

PMID- 17523857
TI  - The effects of a computer-based pregnancy, STD, and HIV prevention intervention:
      a nine-school trial.
AB  - A computer-based intervention was designed to change perceived threat, perceived
      efficacy, attitudes, and knowledge regarding pregnancy, STD, and HIV prevention
      in rural adolescents. The intervention, which was guided largely by the extended
      parallel process model (Witte, 1992), was implemented and evaluated in nine rural
      high schools using an institutional cycle pretest-posttest control-group design
      (Campbell & Stanley, 1963; Cook & Campbell, 1979). Eight-hundred eighty-seven
      ninth-graders completed the survey at both points in time. Process evaluation
      results indicated that the intervention was implemented as intended, and that
      over 91% of students in the treatment group completed at least one of the six
      computer-based activities (M = 3.46, SD = 1.44 for those doing at least one
      activity). Two-way mixed-model repeated-measures analysis of variance revealed
      that students in the treatment group outperformed students in the control group
      on knowledge, condom self-efficacy, attitude toward waiting to have sex, and
      perceived susceptibility to HIV. These results suggest that computer-based
      programs may be a cost-effective and easily replicable means of providing teens
      with basic information and skills necessary to prevent pregnancy, STDs, and HIV.

PMID- 17523858
TI  - How organ donation is represented in newspaper articles in the United States.
AB  - A media agenda setting study was conducted to examine how newspaper stories frame
      the topic of organ and tissue donation. Seven hundred fifteen stories on organ
      and tissue donation from 20 newspapers dated 2002 or 2003 were content-analyzed
      for valence (i.e., positive, negative, or neutral toward organ donation) and
      topic (e.g., living donation, transplant process, celebrity donor/recipient). The
      20 newspapers were chosen by circulation and electronic access of database. Four
      of the top 5 and 13 of the top 20 circulating newspapers were included and
      several combinations of search terms were used to identify relevant articles.
      Results indicate that the majority of articles were either positive (57%) or
      neutral (29%) regarding the topic of organ donation. The 4 most common topics
      covered in news articles included: (a) posttransplantation health and welfare,
      (b) information on the shortage of organ donors, (c) living donation, and (d)
      information about the transplantation process. Kidneys (n = 204) and hearts (n =
      120) were the 2 most commonly mentioned organs in the sample of articles. Results
      are discussed and how news articles may shape laypersons' attitudes and
      intentions regarding organ donation is considered.

PMID- 17523859
TI  - Health communication instruction: toward identifying common learning goals,
      course content, and pedagogical strategies to guide curricular development.
AB  - Health communication is a vibrant and growing area of the communication
      discipline, with an abundance of theoretically grounded scholarship and practical
      application at many levels. Despite this growth, there has yet to be a published
      description of health communication pedagogy that could identify common
      conceptual approaches and teaching practices. To help address this gap, an online
      survey of health communication instructors at 77 colleges and universities
      throughout the United States was conducted. The questionnaire elicited
      information about the general characteristics of the institutions and the
      courses, learning goals, content areas, teaching strategies, and pedagogical
      practices. Key limitations are highlighted and some recent systematic curricular
      programs are then presented.

PMID- 17523860
TI  - Health information sources of individuals with cancer and their family members.
AB  - The purpose of this study was to understand health information sources of
      individuals and families impacted by a cancer diagnosis. Overall, the findings
      support the Freimuth, Stein, and Kean (1989) model of health information
      acquisition. The cancer patients and family members who participated reported
      having significantly more health information along the continuum of cancer care,
      from causes to prevention, after a cancer diagnosis. Although a wide variety of
      interpersonal and mediated information sources are available, participants
      reported that the only consistently (88.1%) used source of information was
      doctors. The most important information sources were, in descending order,
      doctors, family members, nurses, friends, the Internet, other medical personnel,
      and other patients. Individuals, however, were most satisfied with family and
      friends as sources of information, followed by nurses, other patients, and
      doctors. Patients and family members rated the importance of and their
      satisfaction with various information sources differently. Patients rated nurses,
      other medical personnel, and support groups as more important than did family
      members, and patients were significantly more satisfied with doctors and nurses,
      whereas family members were significantly more satisfied with the Internet.

PMID- 17523861
TI  - Health communication resources for uninsured and insured Hispanics.
AB  - There are increasing numbers of medically uninsured populations in the United
      States today. Despite rising concerns with the health status of the uninsured, a
      dearth of information exists about their health seeking and health communication
      behaviors. Because Hispanics experience elevated risks of being medically
      uninsured, and have less access to health care services and health information
      resources, it is imperative that health communicators understand ways to reach
      this population. This study investigates Hispanics' connections to various media
      and interpersonal resources for health information and explores the extent to
      which the uninsured and the insured differ in terms of their health communication
      choices, and health seeking behaviors. Results from a survey of 737 Hispanics in
      Los Angeles show that ethnically targeted television and interpersonal
      communication networks were the preferred sources of health information. The
      uninsured and insured populations differed significantly in the ways that they
      access health care and seek health information, including the use of online
      health information. Implications of the findings are discussed for understanding
      health knowledge gaps and the design of mediated health communication campaigns
      to reach the medically vulnerable and Hispanic populations.

PMID- 17523862
TI  - Differing effects of mass and interpersonal communication on breast cancer risk
      estimates: an exploratory study of college students and their mothers.
AB  - Research has demonstrated that women tend to overestimate the percentage of all
      breast cancers that result from genetic predispositions, and this article
      examines the knowledge of college students, as well as their mothers, on this
      subject, applying uncertainty management (Brashers, 2001) as the theoretical
      framework. The authors build on the literature by studying (a) the types of media
      outlets college students and their mothers use for securing information, and (b)
      the types of articles and programs within those outlets that may affect risk
      perceptions. The authors also address associations between these mass
      communication measures and interpersonal sources of information in the context of
      risk estimation. Respondents exposed to media reports about the role of genetics
      in breast cancer, in addition to study participants who had discussed this role
      within the family, tended to overestimate measures of genetic risk. Conversely,
      those who had attended to media reports about screening practices tended to offer
      lower risk estimates, indicating that such reports may have positioned genetics
      as just one factor in the overall equation of breast cancer risk. The authors
      discuss the implications of these and other findings for communication scholars
      and health practitioners.

PMID- 17523863
TI  - The impact of patient participation on physicians' information provision during a
      primary care medical interview.
AB  - This study investigated the impact of patients' participation on physicians'
      information provision during a primary care medical interview. When communicating
      with high-participation patients, physicians provided significantly more
      information overall, more information in response to patients' questions, and
      volunteered more information than when interacting with low-participation
      patients. The most significant differences with respect to volunteered
      information involved communication about treatment and tests or procedures. These
      results were interpreted to suggest that high-participation patients'
      communication style promotes better alignment of patients' and physicians' goals
      and agendas. Overall, the results suggest that patients' style of participation
      during a medical interview significantly influenced the extent and type of
      information physicians provided. Given that patients' biggest complaint about
      physicians often is a lack of desired information, this study has important
      implications for physician-patient communication.

PMID- 17523864
TI  - Centralizing context and culture in the co-construction of health: localizing and
      vocalizing health meanings in rural India.
AB  - A growing number of communication scholars have articulated the need for
      understanding context as a key component of health meanings. In this project, the
      authors seek to explore the role of context in the domain of health meanings in
      tribal India. The tribal population in India comprises people who have been
      consistently isolated and exploited, and stripped of their rights and resources.
      Interest in their health is propelled by this marginalization and their existence
      in the twilight of tradition and modernization. This article, through the use of
      participant narratives and a grounded theory of analysis, aims to lay out how
      meanings of health are contextually constructed by tribals in India. The results
      demonstrate the constant pain and hardship that envelop their lives, their pining
      for structural capabilities, and a dialectical tension between tradition and
      modernization in the coexistence of multiple treatment options.

PMID- 17523865
TI  - Bibliography.

PMID- 17523866
TI  - Another road to interferon: Yasuichi Nagano's journey.

PMID- 17523867
TI  - IFN-gamma therapy of tuberculosis and related infections.
AB  - It is firmly established that interferon-gamma (IFN-gamma) plays a mandatory role
      in acquired protective immunity to pathogenic mycobacteria and other
      intracellular pathogens. Therefore, it seems conceivable that application of
      recombinant IFN-gamma could be exploited for the treatment of tuberculosis.
      However, the results of experimental studies and clinical trials, conducted
      mostly in patients with multidrug resistant (MDR) disease, have thus far been
      only moderately encouraging. Further studies are now needed to determine if a
      greater clinical benefit from IFN-gamma could be obtained for the prophylactic
      treatment of latent tuberculosis infection and for shortening of the protracted
      standard chemotherapy regimen. Thus, aerosolized IFN-gamma treatment could be
      particularly beneficial to AIDS patients at high risk of developing mycobacterial
      infections, that is, those with significantly declined CD4(+) T cell counts. This
      review describes the current state of research on IFN-gamma interventions in
      tuberculosis and related infections and highlights some of the future
      opportunities.

PMID- 17523868
TI  - Herpes simplex virus blocks Fas-mediated apoptosis independent of viral
      activation of NF-kappaB in human epithelial HEp-2 cells.
AB  - The goal of our study was to characterize the apoptotic response of herpes
      simplex virus (HSV)-infected, human epithelial HEp-2 cells to extrinsic
      treatments through the Fas receptor. Initially, we defined the Fas response of
      these cells. We found the following: (1) Treatment of HEp-2 cells with anti-Fas
      antibody or Fas ligand (FasL) alone did not induce apoptosis. (2) In addition,
      these inducers did not activate NF-kappaB in these cells. (3) The addition of
      cycloheximide (CHX) during these treatments caused a dramatic increase in
      programmed cell death. (4) HEp-2 cells infected with HSV for 6 h prior to anti
      Fas plus CHX treatment were nonapoptotic, and (5) these cells possessed nuclear
      NFkappaB. (6) HSV blocked anti-Fas or FasL plus CHX-induced apoptosis in HEp-2
      cells that stably expressed a dominant-negative form of IkappaBalpha. These
      results indicate that HSV infection can block the process of Fas-mediated
      apoptosis through a mechanism that is independent of viral activation of
      NFkappaB. Our findings help define the molecular mechanisms involved in HSV
      evasion of the cytokine-driven, innate immune response in human epithelial cells.

PMID- 17523869
TI  - Systemic production of IFN-alpha by garlic (Allium sativum) in humans.
AB  - The effect of foods on the production of interferon-alpha (IFN-alpha) is
      currently unknown. Garlic (Allium sativum) used as a folk medicine is reported to
      stimulate nitric oxide (NO) production. We investigated the systemic increase of
      NO due to the ingestion of garlic on the plasma IFN-alpha level in normal
      volunteers. Normal volunteers (10 groups, 10 in each group) ate 2 g fresh garlic,
      and plasma NO and IFN-alpha levels were determined after 2 and 4 h. The
      participants were also asked to eat garlic for various periods of time, and
      plasma NO and IFN-alpha were similarly assayed. Ingestion of 2 g fresh, but not
      boiled, garlic was found to increase the basal plasma level of NO from 2.7 +/-
      0.1 microM to 8.76 +/- 0.21 microM at 2 and 4 h, respectively. The basal plasma
      IFN-alpha level increased from 9.51 +/- 0.26 nM to 46.3 +/- 1.2 nM in normal
      volunteers (n = 10) at the same time. The chronic eating of garlic was found to
      maintain IFN-alpha at high levels for at least 7 days. The exposure of
      neutrophils to garlic in vivo or in vitro, which also stimulated synthesis of NO
      in these cells, was found to stimulate IFN-alpha synthesis as measured by the
      stimulation of IFN-alpha mRNA synthesis. Thus, consumption of garlic resulted in
      stimulated synthesis of NO and, in turn, IFN-alpha in humans, which could be
      beneficial in viral or proliferative diseases.

PMID- 17523870
TI  - The IFN-beta and retinoic acid-induced cell death regulator GRIM-19 is
      upregulated during focal cerebral ischemia.
AB  - The induction of GRIM-19 has been shown to be essential for interferon-beta (IFN
      beta)-induced and retinoic acid (RA)-induced tumor cell death. We have studied
      the localization and levels of GRIM-19 in IFN/RA-induced cell death in neural
      cells and in focal cerebral ischemia. Exposure to IFN/RA caused a approximately
      15-fold increase in GRIM-19 protein levels and induced >50% cell death in human
      neuroblastoma SH-SY5Y cells. In rats subjected to permanent focal cerebral
      ischemia, increased oxidative stress, as well as increased GRIM mRNA levels (32
      fold) and increased GRIM-19 (>50%) protein levels were noted in the ipsilateral
      (affected) hemisphere compared with the contralateral (unaffected) hemisphere.
      These results suggest that GRIM-19 may play a role in ischemia-induced neuronal
      cell death.

PMID- 17523871
TI  - Value of vaginal fluid proinflammatory cytokines for the prediction of early
      onset neonatal infection in preterm premature rupture of the membranes.
AB  - The usefulness of vaginal fluid proinflammatory cytokine assays in the prediction
      of neonatal congenital infection was evaluated. Sixty-two women between 24 and 34
      weeks of pregnancy, complicated by premature rupture of the membranes, were
      divided into those who delivered newborns with (n = 21) and without (n = 41)
      signs of infection. Concentrations of all studied cytokines were higher in women
      who delivered babies with infection. The cutoff values of interleukin-1alpha (IL
      1alpha) and IL-1beta > or = 400, IL-6 > or = 2000, and IL-8 > or = 2100 pg/mL
      predicted infection with a sensitivity of 57%, 57%, 33%, and 76%, a specificity
      of 73%, 73%, 93%, and 59%, a positive predictive value of 52%, 52%, 70%, and 48%,
      and a negative predictive value of 77%, 77%, 73%, and 83%, respectively. Receiver
      operating characteristic (ROC) curve analysis revealed that the predictive
      performance of the four studied cytokines was comparable. In conclusion, vaginal
      fluid cytokines after premature rupture of the membranes have moderately
      predictive value of whether or not a neonate will develop early sepsis.

PMID- 17523872
TI  - Role of endogenous IFN-gamma in macrophage programming induced by IL-12 and IL
      18.
AB  - Besides the established role of interleukin-12 (IL-12) and IL-18 on interferon
      gamma (IFN-gamma) production by natural killer (NK), T, and B cells, the effects
      of these cytokines on macrophages are largely unknown. Here, we investigated the
      role of IL-12/IL-18 on nitric oxide (NO) and tumor necrosis factor-alpha (TNF
      alpha) production by CD11b(+) adherent peritoneal cells, focusing on the
      involvement of endogenously produced IFN-gamma. C57BL/6 cells released
      substantial amounts of NO when stimulated with IFN-gamma or lipopolysaccharide
      (LPS), but failed to respond to IL-12 or IL-18 or both. However, IL-12/IL-18
      pretreatment was able to program these cells to release 6-8-fold more NO and TNF
      alpha in response to LPS or Trypanosoma cruzi stimulation, with NO levels
      directly correlating with macrophage resistance to intracellular parasite growth.
      Analysis of IL-12/IL-18-primed cells from mice deficient in IFN-gamma, IFNGR, and
      IFN regulatory factor-1 (IRF-1) revealed that these molecules were essential for
      LPS-induced NO release, but TNF-alpha production was IFN-gamma independent.
      Conversely, the myeloid differentiation factor 88 (MyD88)-dependent pathway was
      indispensable for IL-12/IL-18-programmed LPS-induced TNF-alpha production, but
      not for NO release. Contaminant T and NK cells largely modulated the IL-12/IL-18
      programming of LPS-induced NO response through IFN-gamma secretion. Nevertheless,
      a small population of IFN-gamma(+) cells with a macrophage phenotype was also
      identified, particularly in the peritoneum of chronically T. cruzi-infected mice,
      reinforcing the notion that macrophages can be an alternative source of IFN
      gamma. Taken together, our data contribute to elucidate the molecular basis of
      the IL-12/IL-18 autocrine pathway of macrophage activation, showing that
      endogenous IFN-gamma plays an important role in programming the NO response,
      whereas the TNF-alpha response occurs through an IFN-gamma-independent pathway.

PMID- 17523873
TI  - Stat1 required for interferon-inducible but not constitutive responsiveness to
      extracellular dsRNA.
AB  - Distinct but partially overlapping signaling pathways mediate the response to
      extracellular vs. intracellular sources of dsRNA, by toll-like receptor 3 (TLR3)
      and retinoic acid-inducible gene-I/melanoma differentiated gene 5 (RIG-I/mda-5),
      respectively. Different cell types signal through these pathways to widely
      varying de grees. We previously observed that exposure to extracellular dsRNA,
      delivered by its addition to the culture medium, could induce the interferon
      (IFN)-stimulated gene 56 (ISG56) in human HT1080 fibrosarcoma cells, but not the
      HT1080-derived cell line, U3A, which lacks functional Stat1. In this study, we
      further investigated the nature of the dsRNA signaling defect in U3A cells. We
      show that a defect affecting basal TLR3 mRNA expression prevents U3A cells from
      responding to extracellular dsRNA. This defect does not impair dsRNA signaling in
      response to viral infection or transfected dsRNA. Although U3A cells are
      deficient in Stat1, we found that Stat1 was not required for basal TLR3
      expression because other cell lines lacking Stat1 expressed TLR3. Moreover,
      restoration of Stat1 expression failed to restore TLR3 mRNA expression in U3A
      cells. However, treatment of Stat1-restored U3A cells with either IFN-beta or IFN
      gamma induced TLR3 expression and restored responsiveness to extracellular dsRNA.
      Our results demonstrate that Stat1 is critical for IFN-induced, not basal,
      responsiveness to extracellular dsRNA.

PMID- 17523874
TI  - Cytokine- and interferon-modulating properties of Echinacea spp. root tinctures
      stored at -20 degrees C for 2 years.
AB  - Echinacea spp. phytomedicines are popular for treating upper respiratory
      infections. The purpose of this investigation was to examine the immunomodulatory
      properties of Echinacea tinctures from seven species after being stored at -20
      degrees C for 2 years. Two experimental techniques were employed using human
      peripheral blood mononuclear cells (PBMC). In the first set of experiments, PBMCs
      were stimulated in vitro with tinctures alone and assayed for proliferation and
      production of interleukin-10 (IL-10), IL-12, and tumor necrosis factor-alpha (TNF
      alpha). In the second set of experiments, subjects were immunized with influenza
      vaccine. PBMCs from vaccinated individuals were stimulated in vitro with
      Echinacea tinctures and influenza virus; cytokine production (IL-2, IL-10, and
      interferon-gamma [IFN-gamma]) was compared prevaccination and postvaccination. In
      the first experiments, (1) tinctures from E. angustifolia, E. pallida, E.
      paradoxa, and E. tennesseensis stimulated proliferation and tended to increase IL
      10, (2) E. sanguinea and E. simulata stimulated only proliferation, (3) E.
      purpurea stimulated only IL-10, and (4) none of the extracts influenced IL-12 or
      TNF-alpha. In the second experiments, (1) tinctures from E. pallida, E. paradoxa,
      E. sanguinea, and E. simulata diminished influenza-specific IL-2, and (2) none of
      the extracts influenced influenza-specific IL-10 or IFN-gamma. For in vitro
      models using Echinacea, immune response may vary based on stimulus (Echinacea
      alone vs. Echinacea + recall stimulation with virus).

PMID- 17523876
TI  - Mitochondrial oxygen consumption and reactive oxygen species production are
      independently modulated: implications for aging studies.
AB  - Various recent investigations relevant to the study of aging mechanisms have
      recently found that increases in longevity during dietary restriction can occur
      together with lack of decreases or even increases in O2 consumption. This is
      frequently interpreted as contradictory with the mitochondrial free radical
      theory of aging. But this is based on the erroneous assumption that increasing O2
      consumption must increase the rate of mitochondrial oxygen radical generation.
      Here it is shown that the opposite occurs in many important situations. Strong
      decreases in absolute and relative (per unit of O2 consumed) mitochondrial oxygen
      radical production occur during aerobic exercise bouts, chronic exercise
      training, and hyperthyroidism, and notably, during dietary restriction.
      Mitochondrial oxygen radical generation is also lower in long-lived birds than in
      short-lived mammals of similar body size and metabolic rate. Total rates of
      reactive oxygen species generation can also vary between tissues in a way not
      linked to their differences in oxygen consumption. All this indicates that
      mitochondrial reactive oxygen species (ROS) production is not a simple byproduct
      of mitochondrial respiration. Instead, it is regulated independently of O2
      consumption in many different physiologic situations, tissues, and animal
      species. Thus, the apparently paradoxical increases in O2 consumption observed in
      some models of dietary restriction do not discredit the mitochondrial free
      radical theory of aging, and they can further strengthen it.

PMID- 17523877
TI  - Vascularization and improved in vivo survival of VEGF-secreting cells
      microencapsulated in HEMA-MMA.
AB  - Vascularization caused by encapsulated cells engineered to secrete vascular
      endothelial growth factor (VEGF) improved the in vivo survival of the
      encapsulated cells in a syngeneic mouse Matrigel plug model. Murine fibroblast
      cells (L929) were engineered to secrete recombinant human vascular endothelial
      growth factor (rhVEGF(165)). Transfected and nontransfected L929 cells were
      microencapsulated in a 75:25 hydroxyethyl methacrylate-methyl methacrylate (HEMA
      MMA) copolymer. Capsules containing transfected cells induced vascularization in
      vivo at 1 and 3 weeks postimplantation. In histological sections, a significant
      positive correlation was seen between the number of capsules and blood vessel
      density for VEGF-secreting cell capsule implants. New vessels, many positively
      stained for smooth muscle cells and pericytes, were seen surrounding these VEGF
      secreting cell capsule explants. Few vessels were seen in nontransfected L929
      capsule implants. The viability of transfected and nontransfected encapsulated
      cells was assessed on explantation. Although the viability of all encapsulated
      cells decreased at both 1 and 3 weeks, encapsulated VEGF-secreting cells retained
      more of the viability than did encapsulated nontransfected control cells.
      Genetically modified cells promoted vascularization in this context and appeared
      to enhance the viability of the encapsulated cells, although the extent of the
      functional benefit was less than expected. Additional effort is required to
      enhance the benefit, to quantify it, and to understand further the host response
      to HEMA-MMA microencapsulated cells and tissue constructs, more generally.

PMID- 17523878
TI  - Cross-linking electrospun type II collagen tissue engineering scaffolds with
      carbodiimide in ethanol.
AB  - In trying to assess the structural integrity of electrospun type II collagen
      scaffolds, a modified but new technique for cross-linking collagen has been
      developed. Carbodiimides have been previously used to cross-link collagen in gels
      and in lyophilized native tissue specimens but had not been used for electrospun
      mats until recently. This cross-linking agent, and in particular 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide hydrochloride (EDC), is of extreme interest,
      especially for tissue-engineered scaffolds composed specifically of native
      polymers (e.g., collagen), because it is a zero-length cross-linking agent that
      has not been shown to cause any cytotoxic reactions. The unique aspect of the
      cross-linking protocol in this study involves the use of ethanol as the solvent
      for the cross-linking agent, because the pure collagen electrospun mats
      immediately disintegrate when placed in an aqueous solution. This study examines
      2 concentrations of EDC with and without the addition of N-hydroxysuccinimide to
      the reaction (which has been shown to result in higher cross-linking yields in
      aqueous solutions) to test the hypothesis that the use of EDC in a nonaqueous
      solution will cross-link electrospun type II collagen fibrous matrices in a
      comparable manner to typical glutaraldehyde fixation protocols. The use of EDC is
      compared with the cross-linking effects of glutaraldehyde via mechanical testing
      (uniaxial tensile testing) and biochemical testing (analysis of the percentage of
      free amino groups). The stress-strain curves of the cross-linked samples
      demonstrated uniaxial tensile behavior more characteristic of native tissue than
      do the dry, untreated samples. The heated, 50% glutaraldehyde cross-linking
      protocol resulted in a mean peak stress of 0.76 MPa, a mean strain at break of
      127.30%, and a mean tangential modulus of 0.89 MPa; mean values for the samples
      treated with the EDC protocols ranged from 0.35 to 0.60 MPa for peak stress, from
      111.83 to 159.23% for strain at break, and from 0.57 to 0.92 MPa for tangential
      modulus. Low and high concentrations (20 mM and 200 mM, respectively) of EDC
      alone were comparable in extent of cross-linking (29% and 29%, respectively) to
      the heated 50% glutaraldehyde cross-linking protocol (30% cross-linked).

PMID- 17523879
TI  - The sequential expression profiles of growth factors from osteoprogenitors
      [correction of osteroprogenitors] to osteoblasts in vitro.
AB  - In this study, we delineate the sequential expression of selected growth factors
      associated with bone formation in vitro. Mineralization, osteocalcin, and
      alkaline phosphatase (ALP-2) were measured to monitor the differentiation and
      maturation of osteoprogenitor cells collected from C57BL mice. Bone-related
      growth factors, including transforming growth factor beta (TGF-beta), fibroblast
      growth factor 2 (FGF-2), platelet-derived growth factor (PDGF), insulinlike
      growth factor (IGF)-1, vascular endothelial growth factor (VEGF), bone
      morphogenetic protein (BMP)-2, and BMP-7, were selected. Enzyme-linked
      immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction
      (RT-PCR) were used to measure growth factors at the protein and messenger
      ribonucleic acid (mRNA) level, respectively. The results found that ALP-2
      expression increased progressively over time, whereas mineralization and
      osteocalcin did not become evident until culture day 14. VEGF and IGF-1 were
      upregulated early during proliferation. PDGF and TGF-beta mRNA expression was
      bimodal. FGF-2 and BMP-2 mRNAs were expressed only later in differentiation. FGF
      2 mRNA signal levels were highest at day 14 and remained prominent through day 28
      of culture. BMP-2 showed a similar profile as FGF-2. BMP-7 was not detectable
      using RT-PCR or ELISA. Strong correlations existed for the expression patterns
      between several early-response growth factors (VEGF, TGF-beta, and IGF-1) and
      were also evident for several late-response growth factors (BMP-2, PDGF, and FGF
      2). Differential expression for grouped sets of growth factors occurs during the
      temporal acquisition of bone-specific markers as osteoprogenitor cell maturation
      proceeds in vitro.

PMID- 17523880
TI  - Scientific investigation of brain-behavior relationships using the Halstead
      Reitan Battery.
AB  - The Reitan Society recognizes that adhering to the scientific method in
      conducting clinical neuropsychological evaluations is integral to neurodiagnostic
      accuracy. The role of science in clinical studies is discussed with specific
      reference to the scientific features of the Halstead-Reitan Test Battery (HRB).
      The diagnostic precision of the HRB across a wide range of neuropathological
      states is presented as a product of rigorous scientific interplay between
      empirical observation and the development of a conceptual model over more than
      five decades.

PMID- 17523881
TI  - Modified scoring criteria for the RBANS figures.
AB  - Visual construction and memory tasks are routinely used in neuropsychological
      assessment, but their subjective scoring criteria can negatively affect the
      reliability of these instruments. The current study examined the standard scoring
      criteria for the Figure Copy and Recall subtests of the RBANS and compared them
      to a modified set of scoring criteria in two samples. In both a large community
      dwelling sample of older adults and in a mixed clinical sample, the original
      scoring criteria consistently led to lower scores than the modified criteria.
      Inter-rater reliability was high for the modified scoring criteria, and no age
      effects were found with the modified scoring criteria. In both samples, the
      modified scoring criteria led to Figure Copy scores that more closely
      approximated other performances on the RBANS compared to the standard criteria,
      whereas both scoring systems led to plausible Figure Recall scores. Despite these
      results, the present study cannot identify one scoring criterion as the "better,"
      but only points out the significant differences between them. Such differences
      can have important clinical implications, and practitioners and researchers who
      utilize the RBANS with patient samples should be cautious when interpreting low
      scores on Figure Copy and Recall if the standard criteria are used.

PMID- 17523882
TI  - Comparability of the GMI and DMI for the WMS-III.
AB  - This study compared the new Delayed Memory (DMI) with the General Memory (GMI)
      index of the WMS-III using 134 inpatients with substance abuse disorders. The WMS
      III Immediate Memory Index (IMI) and the GMI are not parallel because the latter
      includes Auditory Recognition Delayed. A solution to this dilemma is the DMI, in
      that it directly parallels the original IMI. The GMI and DMI scores were highly
      correlated, r = .98, and mean values differed by<1 point (90.77 and 90.66,
      respectively). Difference score comparisons (i.e., IMI-GMI with IMI-DMI and FSIQ
      GMI with FSIQ-DMI) yielded similar results (ts<1). Case-by-case analyses
      demonstrated concordance rates of 99% for the IMI-GMI and IMI-DMI comparisons and
      94% for the FSIQ-GMI and FSIQ-DMI contrasts.

PMID- 17523883
TI  - The effects of practice on speed of information processing using the Adjusting
      Paced Serial Addition Test (Adjusting-PSAT) and the Computerized Tests of
      Information Processing (CTIP).
AB  - Three experiments were conducted to determine the effects of practice on the
      Adjusting-Paced Serial Addition Task (Adjusting-PSAT) (Tombaugh, 1999) and the
      Computerized Tests of Information Processing (CTIP) (Tombaugh & Rees, 2000). The
      Adjusting-PSAT is a computerized modification of the Paced Auditory Serial
      Addition Test (PASAT) (Gronwall, 1977) that makes the interval between digits
      contingent on the correctness of the response. This titration procedure permits a
      threshold value to be derived that represents the shortest presentation interval
      in which a person can process the digits to produce the correct sum. The CTIP
      consists of three reaction time tests that are progressively more difficult.
      Results showed that robust practice effects occurred with the Adjusting-PSAT,
      with the greatest increase in performance occurring on the first retest trial.
      Practice effects were equally prominent regardless of whether the first retest
      trial occurred 20A min, 1 week, or 3 months after the first administration. These
      gains were maintained for periods up to 6 months and were independent of modality
      of presentation (visual or auditory) and type of number list (easy or hard). In
      contrast to the findings with the Adjusting-PSAT, only minimal practice effects
      were observed with the CTIP. The major clinical implication of the study is that
      the high reliability coefficients for the CTIP, the lack of anxiety associated
      with its administration, and its insensitivity to variables such as numerical and
      verbal ability make the CTIP ideally suited for the serial evaluation of
      cognitive status. These characteristics also make the CTIP a viable alternative
      to the Adjusting-PSAT or PASAT for measuring speed of information processing. If
      the Adjusting-PSAT is administered repeatedly in clinical evaluations, a "dual
      baseline" or "run in" procedure should be used, with the second administration
      serving as the baseline measurement.

PMID- 17523884
TI  - PASAT in detecting cognitive impairment in relapsing-remitting MS.
AB  - The PASAT, as a part of the Multiple Sclerosis Functional Composite, is used as a
      sole measure of cognition in multiple sclerosis (MS) clinical trials. In the
      present study, we evaluated the frequency and characteristics of cognitive
      impairment among relapsing-remitting MS patients. Using a comprehensive
      neuropsychological examination as the "golden standard," we assessed PASAT's
      sensitivity and specificity in MS-related cognitive impairment as well as factors
      possibly confounding PASAT performance. Forty-five relapsing-remitting MS
      patients and 48 healthy controls were studied using PASAT and a comprehensive
      neuropsychological examination. The frequency of cognitive dysfunction among MS
      patients was 42%. Cognitive impairment in MS was heterogeneous in nature but
      characterized, especially, by reduced information-processing ability and memory
      deficits. PASAT's sensitivity for patients' cognitive impairment was 74% and
      specificity 65%. Misclassification of cognitive impairment seemed to be
      associated with self-reported nervousness and poor arithmetic skills. Although
      PASAT offers satisfactory sensitivity in detecting the presence of cognitive
      impairment, its specificity may be limited by confounding factors.

PMID- 17523885
TI  - Differentiating malingering from genuine cognitive dysfunction using the Trail
      Making Test-ratio and Stroop Interference scores.
AB  - Patterns of test performance that are inconsistent with knowledge of brain
      dysfunction can potentially differentiate between malingering and true impairment
      among litigants with low scores on neuropsychological tests. In this study
      possible malingerers (n = 41), impaired (30) or cognitively normal (17) litigants
      were compared on the Trail Making Test B:A ratio score and Stroop Interference.
      The majority of possible malingerers had a low TMT-ratio (<2.5) and an inverted
      Stroop effect, whereas the majority of impaired subjects had a high TMT-ratio and
      specific Stroop interference. Sensitivity to malingering was 61 and 68 percent,
      and specificity was 57 and 59 percent. This is too low for valid classification
      of individuals. However, the combination of both measures increases
      predictability. The clinician is advised to look for other evidence of
      malingering in cases of simultaneous low TMT-ratio and inverted Stroop. Patients
      with high TMT-ratio and Stroop interference, should be thoroughly examined for
      indications of brain disease.

PMID- 17523887
TI  - Russell-Silver syndrome and nonverbal learning disability: a case study.
AB  - Russell-Silver Syndrome (RSS) is a rare genetic developmental disorder
      characterized by prenatal and postnatal growth delays and other physical
      abnormalities. Neuropsychological screening was completed with LP, a 20-year-old
      college male diagnosed at one year of age with Russell-Silver Syndrome. LP's
      history and test findings yielded a profile consistent with a nonverbal learning
      disability, with significantly higher verbal compared to nonverbal intelligence,
      deficient visual-spatial memory, fine motor coordination and motor planning
      problems, relatively greater difficulty in math compared to other achievement
      areas, decreased writing fluency, and social behavior impediments. LP also
      experienced attention and concentration problems along with a ruminative
      cognitive-emotional style and mild depression. His pattern of processing
      weaknesses indicated a need for academic accommodations to complete his college
      level academic work, along with counseling to address emotional issues. Further
      studies of individuals with RSS should consider neuropsychological assessment to
      address patterns of cognitive processing and possible need for educational and
      psychosocial intervention.

PMID- 17523889
TI  - Test review: Wide Range Assessment of Memory and Learning-2 (WRAML-2):
      WRedesigned and WReally improved.

PMID- 17523890
TI  - Use of nonintegrating lentiviral vectors for gene therapy.
AB  - Vectors based on lentiviruses have become potent tools for efficient gene
      transfer to multiple cell types both in vitro and in vivo. In part this is
      attributable to the stability of transduction afforded by integration into the
      target cell genome. However, evidence indicates that episomal forms of the vector
      can also be harnessed for effective gene expression. Nonintegrating vectors
      retain the high transduction efficiency and broad tropism of conventional
      lentiviruses but avoid the potential problems associated with the nonspecific
      integration of a transgene. In this respect they are particularly useful in
      postmitotic tissue because the vector genome is not diluted out through cell
      division. Here we discuss the various mutations that may be introduced into human
      immunodeficiency virus-based lentiviral vectors to achieve efficient
      transduction, and the mechanisms by which these vectors are effective. We also
      discuss their potential application to gene therapy and the treatment of genetic
      disease.

PMID- 17523894
TI  - Robotic-assisted laparoscopic ureteropyelostomy for treatment of prostatitis
      secondary to ectopic ureteral insertion of a completely duplicated collecting
      system.
AB  - Symptomatic presentation of a completely duplicated collecting system with upper
      pole ectopic ureteral insertion is rare in the adult. We present a case of a 52
      year-old man with recurrent prostatitis and hematuria secondary to an ectopic
      ureteral insertion from a left upper-pole moiety in a completely duplicated
      collecting system. He underwent a robot-assisted laparoscopic ureteropyelostomy
      with good results. We describe our technique in this unusual case.

PMID- 17523895
TI  - Laparoscopic nephron-sparing surgery.

PMID- 17523896
TI  - Aid to percutaneous renal access by virtual projection of the ultrasound puncture
      tract onto fluoroscopic images.
AB  - BACKGROUND AND PURPOSE: Percutaneous renal access in the context of percutaneous
      nephrolithotomy (PCNL) is a difficult technique, requiring rapid and precise
      access to a particular calix. We present a computerized system designed to
      improve percutaneous renal access by projecting the ultrasound puncture tract
      onto fluoroscopic images. MATERIALS AND METHODS: The system consists of a
      computer and a localizer allowing spatial localization of the position of the
      various instruments. Without any human intervention, the ultrasound nephrostomy
      tract is superimposed in real time onto fluoroscopic images acquired in various
      views. RESULTS: We tested our approach by laboratory experiments on a phantom.
      Also, after approval by our institution's Ethics Committee, we validated this
      technique in the operating room during PCNL in one patient. CONCLUSION: Our
      system is reliable, and the absence of image-processing procedures makes it
      robust. We have initiated a prospective study to validate this technique both for
      PCNL specialists and as a learning tool.

PMID- 17523897
TI  - Ultrasonography of renal masses using contrast pulse sequence imaging: a pilot
      study.
AB  - BACKGROUND AND PURPOSE: The use of contrast-enhanced ultrasonography for imaging
      of renal masses was first described in 1994. Since then, many new techniques for
      visualization of the effect of microbubble contrast agents have been developed.
      In this pilot study, a small number of patients was investigated with contrast
      pulse sequence imaging (CPS), and the characteristics of this perfusion imaging
      technique were evaluated subjectively and judged against the clinical diagnosis
      and histology findings when available. The purpose of this pilot study was to
      describe CPS imaging in several cases. PATIENTS AND METHODS: Eighteen patients
      with 20 previously identified renal masses were examined with CPS. Perfusion
      imaging was compared with clinical diagnosis and with histologic findings when
      available. RESULTS: Nineteen masses were visible. Various enhancement patterns
      could be observed, and interpretations of CPS characteristics are described. In
      carcinomas, inhomogeneous enhancement patterns were observed, and areas without
      enhancement inside the inhomogeneous lesions corresponded to necrotic areas in
      histologic specimens. All simple cysts and complex benign cysts showed absence of
      enhancement inside or in the wall of the lesion and a regular shape. CONCLUSION:
      To our knowledge, this is the first study in which the characteristics of CPS
      imaging of renal masses have been related to clinical diagnoses and histologic
      features. From the results of this pilot project, we conclude that CPS is a
      promising technique to determine perfusion patterns in the kidney.

PMID- 17523898
TI  - Antegrade pyelography versus unenhanced multidetector CT in the assessment of
      urinary-tract stones after percutaneous nephrostomy insertion: a prospective
      blinded study.
AB  - BACKGROUND AND PURPOSE: In patients with a percutaneous nephrostomy tube (PCN)
      inserted for symptomatic stone disease, antegrade pyelography is an accepted
      modality to assess the collecting system and residual stone status prior to PCN
      removal. Recently, unenhanced multidetector CT (UMDCT) has shown its superiority
      for the assessment of urinary-tract stones. Comparison of UMDCT with antegrade
      pyelography has never been done; hence, our aim was to compare the two methods
      for the assessment of urinary stones in patients with a PCN. PATIENTS AND
      METHODS: Between July 2004 and July 2005, we prospectively imaged 49 consecutive
      patients with known urinary-tract stone disease who had PCN (27 men and 22 women;
      average age 57 +/- 20 years; range 4-88 years). All patients underwent UMDCT and
      antegrade pyelography within 24 hours. Both examinations were prospectively and
      blindly evaluated by two attending radiologists for the presence, location, and
      size of urinary-tract stones. RESULTS: According to the findings of both imaging
      modalities, 18 patients were stone free, and 31 patients had urinary stones. In
      20 of the latter 31 patients (64.5%), the urinary stones were diagnosed only by
      UMDCT. Antegrade pyelography missed renal as well as ureteral stones, with a
      significant mean size (5.1 x 6.2 mm, and 6 x 5.3 mm, respectively). Antegrade
      pyelography missed radiolucent (8/20) as well as radiopaque (12/20) stones. In 11
      of the 31 patients (35.5%), urinary stones were diagnosed by both UMDCT and
      antegrade pyelography. The average size of these renal stones was 6 x 11 mm, and
      the mean ureteral stone size was 11 x 13 mm. In 64% (7/11), the stones were
      radiolucent and in 36% (4/11) radiopaque. There was no patient in whom urinary
      stones were diagnosed by antegrade pyelography but missed by UMDCT. CONCLUSIONS:
      Unenhanced multidetector CT is more accurate than antegrade pyelography via a PCN
      for the assessment of urinary-tract stones, with the advantage of reducing the
      risks of contrast injection side effects.

PMID- 17523899
TI  - Management of difficult kidney stones.

PMID- 17523900
TI  - Impact of renal function on efficacy of extracorporeal shockwave lithotripsy.
AB  - BACKGROUND AND PURPOSE: Adequate urine production and excretion may be important
      for clearance of stone fragments after extracorporeal shockwave lithotripsy
      (SWL). This study evaluated the impact of renal function, measured by
      preoperative serum creatinine concentration, on the efficacy of SWL. PATIENTS AND
      METHODS: From 1986 to 2001, 27,299 patients with urolithiasis were treated with
      Medstone STS lithotripters. Seven hundred ninety-eight of these patients (2.92%)
      had serum creatinine concentrations >or=2.0 mg/dL. Perioperative renal function
      (serum creatinine), treatment parameters, stone-free success rate (no residual
      fragments on plain film), and perioperative complications and procedures were
      recorded. RESULTS: The stone-free rate for patients with serum creatinine values
      from 2.0 to 2.9 mg/dL (56.69%) was significantly less than that seen in patients
      with a creatinine concentration <2.0 mg/dL (66.20%). The retreatment rate and
      secondary-procedure rate were significantly higher in patients with higher serum
      creatinine values (9.62% and 8.92%, respectively) than in those with serum
      creatinine within the normal range (6.07% and 4.27%, respectively). There was no
      significant difference in the stone-free rate, re-treatment rate, and secondary
      procedure rate of patients with serum creatinine >or=3.0 mg/dL in comparison with
      patients with values <2 mg/dL. Complication rates were higher for patients with
      serum creatinine values >4.0 mg/dL (10.91%) than for patients with creatinine
      <2.0 mg/dL (2.62%). CONCLUSIONS: The efficacy of SWL is decreased in patients
      with serum creatinine concentrations of 2.0 to 2.9 mg/dL, and the complication
      rate is higher in patients with serum creatinine >4.0 mg/dL. Preoperative
      counseling may include a discussion of the impact of renal insufficiency on
      success and complication rates associated with SWL.

PMID- 17523901
TI  - The Medstone fixed, mobile, and modular configurations: impact on efficacy.
AB  - PURPOSE: To evaluate the efficacy of three lithotripter configurations that
      utilize the Medstone STS treatment head. PATIENTS AND METHODS: From 1999 through
      2002, 13,131 patients were treated with the Medstone STS fixedsite unit (STS-FIX;
      52%), the mobile coach-transportable unit (STS-MOB; 26%), or the modular
      operating-room unit (STS-T; 22%). All units were staffed by a rotating schedule
      of the same ten SWL-certified radiological technicians. The treating urologists
      reported follow-up that included plain abdominal radiography to document stone
      free rate (no residual fragments) and the need for auxiliary procedures or re
      treatment. An efficiency quotient (EQ) was calculated for each unit. RESULTS: The
      overall stone-free rate for the STS-FIX, STS-MOB, and the STS-T was 59%, 62%, and
      65%, respectively. The STS-FIX had the lowest stone-free rate for lower-pole
      stones (48%) and stones 21 mm to 30 mm (30%) compared with the STS-MOB (57% and
      62%, respectively) and the STS-T (59% and 54%, respectively). However, the STS
      FIX had a higher stone-free rate in the middle ureter (86%) than the STS-T (67%)
      and STS-MOB (65%). The STS-FIX required more post-SWL procedures overall (12%)
      than the STSMOB (4%) and STS-T (5%). The re-treatment rates for the STS-FIX, STS
      MOB, and STS-T were 7%, 6%, and 6%, respectively. The STS-T had the highest
      overall EQ (59) followed by the STS-MOB (56) and the STSFIX (50). CONCLUSIONS:
      New configurations of the STS lithotripter have a significant positive impact on
      efficacy compared with the original fixed machine. Availability of real-time
      fluoroscopy with the STS-T may impact the higher EQ of this machine.

PMID- 17523902
TI  - Instillation of skin, nephrostomy tract, and renal puncture site with ropivacaine
      decreases pain and improves ventilatory function after percutaneous
      nephrolithotomy.
AB  - BACKGROUND AND PURPOSE: Pain after percutaneous nephrolithotomy (PCNL) is well
      investigated, but no optimal management strategy has yet been defined.
      Ventilatory changes after uncomplicated PCNL remain obscure. We investigated
      whether pain can be managed with a combination of a parenteral non-narcotic drug
      and instillation of a local anesthetic into the operative field. We also measured
      ventilatory changes early after PCNL to determine whether this analgesic modality
      improves ventilatory status. PATIENTS AND METHODS: In a randomized blinded study,
      34 well-matched patients underwent PCNL with single subcostal access. At the end
      of the operation, 30 mL of either 0.02% ropivacaine or saline was instilled into
      the renal puncture site, nephrostomy tract, and skin. Postoperatively, patients
      received parenteral metamizol (dipyrone) (500 mg/dose) on demand. Pain visual
      analog score (VAS), peak expiratory flow rate (PEF), and blood-gas analysis were
      performed at 2, 6, and 24 hours postoperatively. The number of analgesic doses
      required was recorded. RESULTS: The VAS at 6 hours, time to first analgesic
      demand, and total analgesic need were significantly lower (P=0.001, 0.008, and
      0.001, respectively) in the ropivacaine group, whereas the PEF at 2 and 6 hours
      was significantly higher (P=0.001 for each). Analgesic use in the first 12 and 24
      hours was lower in this group. Blood-gas analysis was within the normal range in
      both groups. Time of surgery and hemoglobin decrease were not significantly
      different. CONCLUSIONS: A decrease in PEF indicating restricted ventilation
      appears early after PCNL. Because these patients were chosen carefully to have
      normal function preoperatively, this decrease was attributed to nociception. A
      combination of ropivacaine instillation with metamizol decreases pain and
      analgesic use and improves PEF more than use of metamizol alone. Such a
      multimodal pain-management strategy is effective in minimizing postoperative
      opioid use with proper pain management, resulting in better ventilation.

PMID- 17523903
TI  - Preventing migration of stones during fragmentation with thermosensitive polymer.
AB  - PURPOSE: To define a method of stabilizing stones during extracorporeal (SWL) and
      intracorporeal lithotripsy with a thermosensitive polymer. MATERIALS AND METHODS:
      Using a thermosensitive polymer that is either a liquid or a gel, depending on
      the temperature, both calcium oxalate and plaster of Paris phantom stones were
      placed in the polymer gel or saline, and SWL was performed. Comparisons were made
      between the effectiveness of the fragmentation in the two media. Also, in-vivo
      studies using the polymer to prevent migration of ureteral stones were performed
      in swine. Electrohydraulic lithotripsy was used on a small stone implanted in the
      distal ureter with the polymer instilled proximally. Once in the ureter, the
      polymer converted to a gel. After completion of the procedure, the polymer was
      restored to a liquid form by infusion of cold saline and expelled from the
      ureter. Three of the pigs underwent treatment of the stone, convalesced for 7
      days, and then had urine collections from both ureters to compare the glomerular
      filtration rates, fractional sodium excretion, urine/plasma creatinine ratio, and
      urine/plasma urea ratio on the treated and the contralateral (control) sides.
      RESULTS: The polymer did not enhance fragmentation when used with SWL but
      prevented stone migration in the in-vivo studies. The physiologic parameters were
      not significantly different on the treated and the control sides. The polymer was
      easily removed from the ureter by infusing cold water. CONCLUSION: The use of
      this thermosensitive polymer proximal to ureteral stones prevents migration and
      is not traumatic to the ureter.

PMID- 17523904
TI  - Simultaneous bilateral percutaneous nephrolithotomy: a single-center experience.
AB  - PURPOSE: To evaluate the safety and efficacy of simultaneous bilateral
      percutaneous nephrolithotomy (SBPCNL) for bilateral renal calculus disease.
      PATIENTS AND METHODS: A retrospective study was conducted from June 1996 to
      February 2006 involving 38 male and 7 female patients with a mean age of 44 years
      (range 5-73 years) with 90 affected renal units who underwent SBPCNL under
      general anesthesia. Those patients with established nephrostomy tracts were
      excluded from the study group. RESULTS: The average duration of the procedure was
      107 +/- 43 minutes (range 60-220 minutes). The average drop in hemoglobin was 2
      +/- 1.2 g/dL (range 0.3-5.6 g/dL), with 3 patients (7%) requiring blood
      transfusion. In 87% of patients, a single stage was performed on both sides,
      while 13% required two stages on one side. A single tract was on both sides
      utilized in 78%, while 22% of the patients required two tracts on one side. None
      required two tracts on both sides or more than one stage on both sides. The stone
      clearance rate was 96%. The average hospital stay was 6 days. Complications
      consisted of renal-pelvic perforation in two patients and transient pyrexia in
      five. Three patients had persistent urine leak on one side, of which two stopped
      spontaneously and one necessitated ureteral stenting. CONCLUSION: Simultaneous
      bilateral PCNL is a safe procedure and can be used effectively in adults as well
      as in children. In addition to being cost effective, it involves only a single
      anesthesia with a shorter hospital stay and faster convalescence. However,
      patients with a large stone burden or complex pelvicaliceal anatomy should not be
      selected for SBPCNL.

PMID- 17523905
TI  - Quality of life after percutaneous nephrolithotomy for caliceal diverticulum and
      secluded lower-pole renal stones.
AB  - BACKGROUND AND PURPOSE: The treatment of caliceal diverticulum and deeply
      secluded lower-pole stones is challenging, and the indications are controversial.
      This study assessed the changes in the quality of life (QoL) of patients
      undergoing percutaneous nephrolithotomy (PCNL) for symptomatic caliceal
      diverticula and deep lower-pole calculi to determine whether there is a change in
      the "bother factor" in order to improve treatment strategies for this group of
      patients. PATIENTS AND METHODS: Twenty-two patients undergoing PCNL were
      evaluated prospectively using the SF36 QoL questionnaire before and 6 weeks after
      PCNL. The results before and after PCNL were compared individually and by group
      and analyzed statistically. A P value <or=0.05 was considered significant.
      RESULTS: Most (87%) of the patients were completely stone free after the
      procedure. Significant QoL findings were a reduction in symptoms interfering with
      performance at work (40%) and improved general health (33%). Although there was
      an overall improvement in QoL across the entire group, this reached statistical
      significance for only two of the seven domains of the questionnaire. CONCLUSIONS:
      In spite of a high stone-free rate, fewer than half of patients benefited
      subjectively from the procedure in terms of improvement of QoL. Therefore,
      patients should be made aware of the limited impact of surgical treatment on QoL,
      and asymptomatic patients can be given the option of further watchful waiting.

PMID- 17523906
TI  - Percutaneous nephrolithotomy in patients with kidney malformations.
AB  - BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy (PCNL) for complex calculi
      within malformed kidneys can be challenging because of the abnormal anatomy. We
      present our 7-year experience with PCNL in such patients. PATIENTS AND METHODS:
      We performed PCNL on 16 patients with complex calculi and anomalous kidneys,
      including 7 with horseshoe kidneys, 5 with rotation anomalies, 3 with ectopic
      kidneys, and 1 with a small kidney. After appropriate preoperative evaluation,
      the procedure was performed by choosing either anterior or posterior approaches
      depending on the kidney anomaly. When required, ultrasonography, laparoscopy, or
      both were used, as well as fluoroscopy to control the procedures. RESULTS: A
      single-stage PCNL resulted in complete clearance in 13 patients (81%). A second
      look procedure, alone or followed by shockwave lithotripsy, conferred stone
      clearance in one patient with a malrotated kidney and two with staghorn calculi
      in horseshoe kidneys. More than one tract was needed in two patients. The
      procedure was guided by laparoscopy in two patients with calculi in ectopic left
      kidneys. Serious complications were not encountered. CONCLUSION: Patients with
      malformed kidneys and complex calculi can be managed safely and effectively with
      PCNL when they are properly selected and appropriately assessed before operation.

PMID- 17523907
TI  - Laparoscopic transperitoneal ureterolithotomy for recurrent lower-ureteral stones
      previously treated with open ureterolithotomy: initial experience in 11 cases.
AB  - PURPOSE: To evaluate transperitoneal ureterolithotomy by laparoscopy (TPUL) for
      the management of recurrent lower-ureteral stones previously treated with open
      surgery. PATIENTS AND METHODS: Between January 2003 and June 2006, 11 patients
      (mean age 35.2 years) with recurrent large (mean size 2.8 cm) lower-ureteral
      calculi and normal renal function underwent TPUL. Seven stones were on the left
      side, and the remaining four were on the right side. These stones were recurrent
      after previous open ureterolithotomy. Earlier attempts with ureteroscopy (for
      three patients) had failed. RESULTS: The TPUL was successful in all cases. The
      mean operating time was 85.2 minutes. Two patients required no narcotic
      analgesics, while the other patients received a mean of 2.3 10-mg doses of
      morphine sulfate for postoperative pain relief. The mean hospital stay was 3.8
      days. The mean convalescence period was 13.7 days. There were no major
      intraoperative or postoperative complications. Prolonged urine leakage for 7 and
      9 days occurred in two patients, which was managed conservatively. All patients
      were asymptomatic, stone free, and without obstruction or stricture formation on
      follow-up that included abdominal ultrasonography and plain films after 6 weeks
      and intravenous urography after 6 months. There was no deterioration of renal
      function. CONCLUSIONS: Laparoscopic transperitoneal ureterolithotomy is a
      feasible technique for the management of recurrent lower-ureteral stones after
      previous open ureterolithotomy that are not amenable to ureteroscopy or SWL. It
      is a minimally invasive, less-morbid alternative to open transperitoneal
      ureterolithotomy.

PMID- 17523908
TI  - Case report: intrarenal arteriovenous fistula after ureteroscopic stone
      extraction with holmium laser lithotripsy.
AB  - A 79-year-old woman presented with gross hematuria 10 days after flexible
      ureteroscopic stone extraction with holmium laser lithotripsy. Work-up revealed a
      bleeding intrarenal arteriovenous fistula that was embolized. To our knowledge,
      this is the first report of this complication causing delayed hematuria after
      ureterorenoscopy.

PMID- 17523909
TI  - Ureteral expanding stent: a new device for urolithiasis.
AB  - BACKGROUND AND PURPOSE: We investigate a ureteral stent with radially expanding
      baskets producing passive dilation of the ureter for passage, capture, and
      removal of small ureteral stones. PATIENTS AND METHODS: Polyurethane ureteral
      stents were slit to open 15 to 17 baskets along the length. The baskets are
      designed to dilate the ureter passively and capture stones <or=5 mm. Forty-two
      patients had these stents placed for stones at nine medical centers. Stone size
      ranged from 2 to 30 mm, while fragment size ranged from 1 to 8 mm. The locations
      of the stones ranged from the kidney to the lower ureter. The Ureteral Expanding
      Stent was inserted in the closed position, similar to a standard ureteral stent,
      and left in place for an average of 11 days. RESULTS: The device was inserted and
      extracted safely in all patients. Most patients experienced pain at an average
      rating of 3.7 of 10 on a visual analog scale. All stents were removed without
      significant morbidity. In 36 patients (86%), stones were removed with the stent
      (n=18) or passed while the stent was in place (n=18). The largest stone captured
      was 6 mm. CONCLUSIONS: The Ureteral Expanding Stent (OPEN-Pass) was used safely
      in 42 patients with stones. The device captured ureteral stones and facilitated
      stone passage around it. Stent retention or ureteral injury as a result of stone
      entrapment did not occur. The Ureteral Expanding Stent represents a new stone
      removal and ureteral-dilation tool worthy of further clinical study.

PMID- 17523910
TI  - Doxazosin for the management of distal-ureteral stones.
AB  - PURPOSE: To evaluate the efficacy of doxazosin in inducing spontaneous passage of
      stones in the distal ureter and to compare its efficacy according to the size of
      the stone. PATIENTS AND METHODS: Seventy-three patients with a mean age of 46.38
      +/- 10.17 years who presented with a distal-ureteral stone were divided into four
      groups according to stone size and drug treatment: <5 mm without doxazosin (group
      A; n=15); 5-10 mm (group B; n=16); <5 mm with doxazosin 4 mg/day for 4 weeks
      (group C; n=20); and 5-10 mm with doxazosin 4 mg/day for 4 weeks (group D; n=22).
      Groups A and B served as controls for groups C and D, respectively. RESULTS:
      Spontaneous stone passage was documented in 9 patients (60%) in group A v 17
      (85%) in group C (P=0.047) and 7 (43.75%) in group B v 16 (72.73%) in group D
      (P=0.036). The average expulsion time was 8.78 +/- 1.09 days in group A v 7.59 +/
      0.80 days in group C (P=0.004) and 12.14 +/- 1.35 days in group B v 7.06 +/-
      1.29 days in group D (P<0.0001). The number of pain episodes in group D patients
      was significantly lower than in group B (P +/- 0.0078). CONCLUSIONS: Doxazosin
      treatment proved to be safe and effective for distal-ureteral stones, as
      determined by earlier expulsion, decreased colic frequency, and absence of side
      effects. The efficacy of doxazosin was significantly higher for 5-to 10-mm stones
      than for smaller ones.

PMID- 17523911
TI  - Left-sided inferior vena cava found incidentally during laparoscopic donor
      nephrectomy: report of three cases.
AB  - Laparoscopic donor nephrectomy can be a challenging procedure in patients with
      abdominal great-vessel anomalies. We report our experience with three cases of
      laparoscopic donor nephrectomy with a rare incidentally found left-sided inferior
      vena cava.

PMID- 17523912
TI  - A biological model to teach percutaneous nephrolithotomy technique with
      ultrasound- and fluoroscopy-guided access.
AB  - PURPOSE: To develop a training model for simulated percutaneous nephrolithotomy
      (PCNL) under ultrasound and fluoroscopy-guided access. MATERIALS AND METHODS: The
      laboratory model for PCNL described by Hammond and associates (J Urol
      2004;172:1950-1952) was modified. We used an ex-vivo perfused porcine kidney
      (freshly removed after commercial slaughtering), a chicken carcass (supermarket),
      as well as the standard equipment for PCNL. For imaging, ultrasound (7.5 MHz) and
      a fluoroscopy unit are necessary. Artificial stone material is implanted in the
      renal pelvis. The ureter is cannulated for retrograde pyelography and the renal
      artery and vein for continuous perfusion. The perfused kidney surrounded by
      ultrasound gel is placed in the eviscerated chicken carcass. RESULTS: The model
      is low cost and simple to set up, with a preparation time of about 15 minutes.
      The equipment used in clinical practice can be employed for renal access, tract
      dilation, nephroscopy, stone disintegration, and stone removal. Imaging is
      feasible under fluoroscopic and ultrasound guidance. CONCLUSIONS: This biological
      training model simulates realistically the clinical procedure of PCNL under
      ultrasound and fluoroscopic guidance. Teaching and skill acquisition are
      practicable.

PMID- 17523913
TI  - Evaluation of renal defect healing, hemostasis, and urinary fistula after
      laparoscopic partial nephrectomy with oxidized cellulose.
AB  - BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) has been performed
      at several institutions using oxidized cellulose (OC) as a means of bleeding and
      urinary fistula (UF) prevention. However, a foreign-body reaction mimicking
      either abscess or tumor recurrence has been associated with the use of OC. We
      evaluated renal-defect healing after LPN with and without OC. MATERIALS AND
      METHODS: Sixteen female Landrace pigs underwent lower-pole excision; all the
      collecting systems were entered and then closed with absorbable running suture.
      In group 1, hemostatic U-shaped stitches were the only method of hemostasis. In
      group 2, a bolster of OC was added to the renal defect. The pigs were sacrificed
      at 1, 4, 7, or 21 days, and gross findings such as perirenal collection were
      observed. A catheter was advanced up to the kidney, and methylene blue was
      injected with collecting system pressure observation; burst pressure was defined
      as the appearance of extravasation. High risk for UF was defined as burst
      pressure <10 mm Hg. RESULTS: Neither hemorrhage nor urinoma was observed during
      sacrifice. One pig from group 2 had a burst pressure of 4 mm Hg At 7 days (high
      risk for UF). At 21 days in group 2, the tissue was grossly solid, apparently a
      granuloma. Suppuration tended to be greater in group 2. The foreign-body reaction
      was more intense in group 2 and was strongly present at 4, 7, and 21 days.
      CONCLUSIONS: The use of OC is associated with higher scores of suppuration and
      foreign-body reaction. After LPN with OC, postoperative day 7 might be a critical
      time for the development of urinary leakage.

PMID- 17523916
TI  - Proteasome function is required to maintain muscle cellular architecture.
AB  - BACKGROUND INFORMATION: Protein degradation via the UPS (ubiquitin-proteasome
      system) plays critical roles in muscle metabolism and signalling pathways. The
      present study investigates temporal requirements of the UPS in muscle using
      conditional expression of mutant proteasome beta subunits to cause targeted
      inhibition of proteasome function. RESULTS AND CONCLUSIONS: The Drosophila
      GeneSwitch system was used, with analyses of the well-characterized larval
      somatic body wall muscles. This method acutely disrupts proteasome function and
      causes rapid accumulation of polyubiquitinated proteins, specifically within the
      muscle. Within 12 h of transgenic proteasome inhibition, there was a gross
      disorganization of muscle architecture and prominent muscle atrophy, progressing
      to the arrest of all co-ordinated movement by 24 h. Progressive muscle
      architecture changes include rapid loss of sarcomere organization, loss of nuclei
      spacing/patterning, vacuole formation and the accumulation of nuclear and
      cytoplasmic aggregates at the ultrastructural level. At the neuromuscular
      junction, the highly specialized muscle membrane folds of the subsynaptic
      reticulum were rapidly lost. Within 24 h after transgenic proteasome inhibition,
      muscles contained numerous autophagosomes and displayed highly elevated
      expression of the endoplasmic reticulum chaperone GRP78 (glucose-regulated
      protein of 78 kDa), indicating that the loss of muscle maintenance correlates
      with induction of the unfolded protein response. Taken together, these results
      demonstrate that the UPS is acutely required for maintenance of muscle and
      neuromuscular junction architecture, and provides a Drosophila genetic model to
      mechanistically evaluate this requirement.

PMID- 17523917
TI  - Increased antiviral activity of microscale-purified HuIFN alpha 8 (human
      interferon alpha 8) over HuIFN alpha 2b in Hep-2 cells challenged with Mengo
      virus.
AB  - Human proteins are not routinely expressed at high levels in Escherichia coli
      for, among other reasons, different codon usage. Several purification procedures
      have been applied to recover recombinant proteins for further biological
      characterization. However, the vast majority involve costly chromatography
      procedures. In the present study, both (Hu)IFN(alpha 2b) (human interferon alpha
      2b) and (Hu)IFN(alpha 8) were expressed efficiently in E. coli BL21-codonplus
      RIL. Subsequently, both recombinant proteins were purified to homogeneity by
      passive elution from reverse-stained SDS/PAGE gels, a cost-effective purification
      procedure. After purification, both recovered proteins were biologically active.
      The (Hu)IFN(alpha 8) subtype induced 1.46-fold more antiviral activity than
      (Hu)IFN(alpha 2b) using Hep-2 human laryngeal carcinoma cell challenged with
      Mengo virus.

PMID- 17523919
TI  - Soluble expression of human DRR1 (down-regulated in renal cell carcinoma 1) in
      Escherichia coli and preparation of its polyclonal antibodies.
AB  - Human DRR1 (down-regulated in renal cell carcinoma 1) is widely expressed in
      normal tissues but dramatically reduced or even undetectable in a number of
      different cancer cell lines and primary tumour types. DRR1 from Homo sapiens was
      cloned into the pQE30 vector for fusion-protein expression with six histidine
      residues in Escherichia coli BL21(DE3). A soluble protein with a molecular mass
      of approx. 19 kDa on SDS/PAGE that matches the expected rDRR1 (recombinant DRR1)
      molecular mass (18.7 kDa) was obtained. The soluble and insoluble expression of
      recombinant protein DRR1 (rDRR1) was temperature-dependent. The expression rDRR1
      was in soluble and insoluble forms at 37 degrees C, and approx. 80% of total
      rDRR1 was soluble at 37 degrees C, while rDRR1 was almost exclusively expressing
      in soluble form at 20 degrees C. The expressed rDRR1 at 20 degrees C was affinity
      purified on Ni(2+)-charged resin under native conditions. The purified protein
      was further identified by ESI-MS (electrospray ionization MS). The purified
      recombinant protein rDRR1 was further used to raise anti-(human DRR1) polyclonal
      antibodies, which were suitable for detecting both the recombinant exogenous DRR1
      and the endogenous DRR1 from tissues and cells by immunoblotting and
      immunohistochemistry. The purified rDRR1 and our prepared anti-(human DRR1)
      polyclonal antibodies may provide useful tools for future biological function
      studies on DRR1.

PMID- 17523920
TI  - Expression and analysis of thymosin alpha1 concatemer in Escherichia coli.
AB  - Talpha1 (thymosin alpha 1) is important in treating immunodeficiency and other
      diseases. In order to study the feasibility of expressing Talpha1 in plants, as
      the first attempt, we designed and synthesized the Talpha1 gene according to the
      plant codon usage preference and constructed the 4xTalpha1 concatemer (four
      copies of a DNA sequence arranged end-to-end in tandem). The latter was inserted
      into Escherichia coli expression vector pQE30, resulting in a recombinant plasmid
      that was subsequently transformed into E. coli M15. The 4xTalpha1 concatemer
      protein was successfully expressed in E. coli in a soluble form. The expressed
      protein was purified and its bioactivity was analysed by MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay. Preliminary
      results showed that the 4xTalpha1 concatemer protein could stimulate the mice
      spleen lymphocyte proliferation. This is the first report on the expression of
      4xTalpha1 concatemer that was synthesized according to plant codon usage
      preference in an E. coli expression system. The present study provides the basis
      for expressing the synthesized active Talpha1 gene in plants in the future.

PMID- 17523921
TI  - A functionally conserved basic residue in glutathione transferases interacts with
      the glycine moiety of glutathione and is pivotal for enzyme catalysis.
AB  - The present study characterized conserved residues in a GST (glutathione
      transferase) in the active-site region that interacts with glutathione. This
      region of the active site is near the glycine moiety of glutathione and consists
      of a hydrogen bond network. In the GSTD (Delta class GST) studied, adGSTD4-4, the
      network consisted of His(38), Met(39), Asn(47), Gln(49), His(50) and Cys(51). In
      addition to contributing to glutathione binding, this region also had major
      effects on enzyme catalysis, as shown by changes in kinetic parameters and
      substrate-specific activity. The results also suggest that the electron
      distribution of this network plays a role in stabilization of the ionized thiol
      of glutathione as well as impacting on the catalytic rate-limiting step. This
      area constitutes a second glutathione active-site network involved in glutathione
      ionization distinct from a network previously observed interacting with the
      glutamyl end of glutathione. This second network also appears to be functionally
      conserved in GSTs. In the present study, His(50) is the key basic residue
      stabilized by this network, as shown by up to a 300-fold decrease in k(cat) and
      5200-fold decrease in k(cat)/K(m) for glutathione. Although these network
      residues have a minor role in structural integrity, the replaced residues induced
      changes in active-site topography as well as generating positive co-operativity
      towards glutathione. Moreover, this network at the glycine moiety of GSH
      (glutathione) also contributed to the 'base-assisted deprotonation model' for GSH
      ionization. Taken together, the results indicate a critical role for the
      functionally conserved basic residue His(50) and this hydrogen bond network in
      the active site.

PMID- 17523923
TI  - Identification of an oxidative refolding intermediate of recombinant consensus
      interferon from inclusion bodies and design of a two-stage strategy to promote
      correct disulfide-bond formation.
AB  - Dilution refolding of recombinant consensus IFN (interferon) from inclusion
      bodies suffers from low yield. A stable intermediate was found to mix with the
      correct product and to have an antiviral activity of less than 10% of the latter.
      This intermediate would form precipitates upon removal of the precipitation
      inhibitor arginine. Compared with the native protein, the intermediate moved more
      slowly on non-reducing SDS/PAGE. The CD and fluorescence spectra indicated that
      it had formed a native-like structure, but had only one disulfide bond: Cys(29)
      Cys(139). Further evidence showed that the formation of Cys(29)-Cys(139) is
      specific and very likely to happen, even in the presence of a high concentration
      of reducing agent, whereas pairing of the other disulfide (Cys(1)-Cys(99)) needed
      a stronger oxidative condition. It competed with intermolecular disulfide bonding
      to form covalent oligomers. On the basis of this discovery, a two-stage refolding
      step strategy was designed that employed a modified dilution refolding step
      followed by a dialysis refolding step. The first stage used a high concentration
      of reducing agent together with the precipitation inhibitor arginine. The purpose
      was to hinder any reaction through Cys(1) or Cys(99) but allow the intramolecular
      disulfide bonding of Cys(29)-Cys(139). The second stage was a dialysis step that
      gradually increased the oxidative agent concentration and simultaneously
      decreased the arginine concentration. The refolding yield was increased from 35
      to 82%, while the mass recovery was increased from 60 to 96%. Moreover, this
      strategy could suppress precipitation even after arginine was completely removed.

PMID- 17523924
TI  - Differential membrane binding and diacylglycerol recognition by C1 domains of
      RasGRPs.
AB  - RasGRPs (guanine-nucleotide-releasing proteins) are exchange factors for membrane
      bound GTPases. All RasGRP family members contain C1 domains which, in other
      proteins, bind DAG (diacylglycerol) and thus mediate the proximal signal
      transduction events induced by this lipid second messenger. The presence of C1
      domains suggests that all RasGRPs could be regulated by membrane translocation
      driven by C1-DAG interactions. This has been demonstrated for RasGRP1 and
      RasGRP3, but has not been tested directly for RasGRP2, RasGRP4alpha and
      RasGRP4beta. Sequence alignments indicate that all RasGRP C1 domains have the
      potential to bind DAG. In cells, the isolated C1 domains of RasGRP1, RasGRP3 and
      RasGRP4alpha co-localize with membranes and relocalize in response to DAG,
      whereas the C1 domains of RasGRP2 and RasGRP4beta do not. Only the C1 domains of
      RasGRP1, RasGRP3 and RasGRP4alpha recognize DAG as a ligand within phospholipid
      vesicles and do so with differential affinities. Other lipid second messengers
      were screened as ligands for RasGRP C1 domains, but none was found to serve as an
      alternative to DAG. All of the RasGRP C1 domains bound to vesicles which
      contained a high concentration of anionic phospholipids, indicating that this
      could provide a DAG-independent mechanism for membrane binding by C1 domains.
      This concept was supported by demonstrating that the C1 domain of RasGRP2 could
      functionally replace the membrane-binding role of the C1 domain within RasGRP1,
      despite the inability of the RasGRP2 C1 domain to bind DAG. The RasGRP4beta C1
      domain was non-functional when inserted into either RasGRP1 or RasGRP4, implying
      that the alternative splicing which produces this C1 domain eliminates its
      contribution to membrane binding.

PMID- 17523925
TI  - NPC1L1 (Niemann-Pick C1-like 1) mediates sterol-specific unidirectional transport
      of non-esterified cholesterol in McArdle-RH7777 hepatoma cells.
AB  - Recent evidence suggests that NPC1L1 (Niemann-Pick C1-like 1) is critical for
      intestinal sterol absorption in mice, yet mechanisms by which NPC1L1 regulates
      cellular sterol transport are lacking. In the study we used a McArdle-RH7777 rat
      hepatoma cell line stably expressing NPC1L1 to examine the sterol-specificity and
      directionality of NPC1L1-mediated sterol transport. As previously described,
      cholesterol-depletion-driven recycling of NPC1L1 to the cell surface facilitates
      cellular uptake of non-esterified (free) cholesterol. However, it has no impact
      on the uptake of esterified cholesterol, indicating free sterol specificity.
      Interestingly, the endocytic recycling of NPC1L1 was also without effect on beta
      sitosterol uptake, indicating that NPC1L1 can differentiate between free sterols
      of animal and plant origin in hepatoma cells. Furthermore, NPC1L1-driven free
      cholesterol transport was unidirectional, since cellular cholesterol efflux to
      apolipoprotein A-I, high-density lipoprotein or serum was unaffected by NPC1L1
      expression or localization. Additionally, NPC1L1 facilitates mass non-esterified
      cholesterol uptake only when it is located on the cell surface and not when it
      resides intracellularly. Finally, NPC1L1-dependent cholesterol uptake required
      adequate intracellular K(+), yet did not rely on intracellular Ca(2+), the
      cytoskeleton or signalling downstream of protein kinase A, protein kinase C or
      pertussis-toxin-sensitive G-protein-coupled receptors. Collectively, these
      findings support the notion that NPC1L1 can selectively recognize non-esterified
      cholesterol and promote its unidirectional transport into hepatoma cells.

PMID- 17523926
TI  - Genetic factors associated with skin cancer in renal transplant patients.
AB  - BACKGROUND: Non-melanoma skin cancer represents a significant cause of morbidity
      and mortality among renal transplant recipients. Established risk factors that
      increase susceptibility to skin cancer after transplantation include skin type,
      sun exposure and level of immunosuppression. METHODS: A comprehensive literature
      review was carried out to discuss relevant genetic polymorphism for the
      development of skin cancer in organ transplant recipients. These include genetic
      polymorphisms in glutathione S-transferase, interleukin-10, retinoblastoma and
      p53 genes. We also discuss genetic polymorphisms in the folate pathway,
      melanocortin 1 receptor and vitamin D receptor recently discovered in our group.
      RESULTS: No single factor is causative in cutaneous carcinogenesis in transplant
      recipients. Interactions of some of the above mechanisms with known environmental
      factors lead to increased risk. CONCLUSION: Polymorphisms in
      methylenetetrahydrofolate reductase are potentially correctable with folic acid
      supplementation; however, further evaluation is required in adequately powered
      prospective clinical trials. Avoidance of known oncogenic environmental factors
      and genetic risk evaluation may improve outcomes in transplant patients.

PMID- 17523927
TI  - Rate of acute adverse events for narrow-band UVB and Psoralen-UVA phototherapy.
AB  - BACKGROUND: Ultraviolet (UV) radiation therapies are commonly used to treat a
      wide range of dermatological conditions. However, no published data exist
      regarding the rate of acute adverse events occurring within the different UV
      therapy modalities. AIM: The aim of this study was to determine the rate of acute
      adverse events experienced by patients receiving narrow-band UVB or
      photochemotherapy in 3 neighboring dermatology units. METHOD: Standardized
      adverse event forms from all 3 units were retrospectively analysed over a 12
      month period between October 2003 and September 2004. The treatments included
      were narrow-band UVB and systemic, bath and hand/foot PUVA. RESULTS: A total of
      8784 treatments were given over the study period. The total number of acute
      adverse events recorded for all phototherapy treatments was 70 (0.8%). The rates
      of acute adverse events for each treatment modality were 0.6% for narrow-band
      UVB, 1.3% for systemic PUVA, 1.3% for bath PUVA and 0.8% for hand/foot PUVA.
      Adverse events were due to patient non-compliance with standard operating
      procedures in 15 cases (21%) and operator error in 2 (3%). Only 4 of the acute
      adverse events were considered to be severe, accounting for 0.05% of all
      treatments. CONCLUSIONS: The rates of acute adverse events with phototherapy in
      this analysis were low, in particular the rate of severe adverse events. The
      highest rate was seen with both systemic and bath PUVA. The number of adverse
      events resulting from operator error was low. These published rates for adverse
      events associated with narrow-band UVB and PUVA may help other units when
      analyzing their own rate of adverse events.

PMID- 17523928
TI  - In vitro phototoxicity test using artificial skin with melanocytes.
AB  - BACKGROUND: Exposure to ultraviolet radiation (UVR) has been shown to induce
      cutaneous biological changes and phototoxic reactions. OBJECTIVE: This study was
      designed to evaluate the usefulness of artificial skin (AS) composed of
      keratinocytes and melanocytes as an in vitro phototoxicity model for topical
      agents. MATERIALS AND METHODS: AS was manufactured with three-dimensionally
      cultured keratinocytes and melanocytes on a de-epidermized dermis (DED). The
      photobiological responses in AS with and without melanocytes were comparatively
      examined after ultraviolet A (UVA) exposure. Three test chemicals (8
      methoxypsoralen, 6-methylcoumarin and tetracycline) were topically applied onto
      the AS with melanocytes and after UVA irradiation, the released inflammatory
      cytokines (IL-1alpha, IL-beta and IL-6) were analyzed. RESULTS: AS with
      melanocytes showed better epidermal structures, stronger resistance to UVA
      exposure and photobiological responses closer to in vivo human skin. Releases of
      inflammatory cytokines were well correlated with the increased phototoxicities of
      test chemicals. Among the measured cytokines, IL-6 could be the most reliable in
      vitro marker indicative of phototoxic potential, because it showed statistically
      significant increase only in case of concurrent exposure to chemicals and UVA.
      CONCLUSION: The AS with melanocytes may be a useful tool especially for examining
      UV-induced cutaneous changes and a promising in vitro phototoxicity test model
      for topical agents.

PMID- 17523929
TI  - Fox-P3-positive regulatory T cells are present in the skin of generalized atopic
      eczema patients and are not particularly affected by medium-dose UVA1 therapy.
AB  - BACKGROUND: Regulatory T cells (T-reg cells) have been described as an important
      cell population in the UV treatment of inflammatory skin diseases. METHODS: We
      have treated five patients with generalized atopic eczema (AE) using medium-dose
      (15 cycles of 50 J/cm(2), total dose of 750 J/cm(2)) UVA1 therapy and have
      analyzed the skin-infiltrating T-cellular subsets before and after therapy. Skin
      biopsies were split for immunohistochemistry and Real-time PCR and analyzed for
      CD4, Fox-P3, GATA-3, and IL-10 transcription as well as for CD3, CD4, CD152, Fox
      P3, and GITR staining. RESULTS: In all the investigated patients, we observed a
      good clinical response to UVA1. As described previously, the number of epidermal
      T cells slightly declined after irradiation. However, we did not observe a
      general decrease in T cell numbers. Within the population of T cells, no specific
      difference in the kinetics of Fox-P3-positive cells and Fox-P3-specific mRNA was
      noted as compared with GATA-3 positive T cells. These results were paralleled by
      RT-PCR for IL-10 and staining for CD152, a surface molecule that has been
      described for T-reg cells. CONCLUSION: In our hands, the clinical benefit of UVA1
      treatment in AE patients does not seem to be due to a preferential
      survival/proliferation of T-reg cells.

PMID- 17523930
TI  - Topical application of plant extracts containing xanthine derivatives can prevent
      UV-induced wrinkle formation in hairless mice.
AB  - BACKGROUND: Plants are the source of important products with nutritional and
      therapeutic value. Topical or oral administration of some plant extracts has been
      shown to reduce photodamage. Cacao bean and cola nut are popular edible plants
      that contain polyphenols and xanthine derivatives. These plant extracts possess
      protective effects against UV-induced erythema when taken orally, and an H(2)O(2)
      scavenging effect. METHODS: Plant extracts containing xanthine derivatives and
      three xanthine derivatives were topically applied to the dorsal skin of hairless
      mice, and the mice were exposed to a resemblance of solar ultraviolet irradiation
      at a dose of 13.0 J/cm(2) (UVA) for 15 weeks, five times a week on weekdays.
      After the final irradiation, histological, and analytical studies were performed.
      RESULTS: Topical application of plant extracts (cacao beans, cola nuts) and
      caffeine, theobromine, and theophylline markedly prevented photodamage including
      wrinkle formation and histological alterations. A significant increase in total
      hydroxyproline content caused by UV irradiation was observed. In contrast,
      topical application of plant extracts and xanthine derivatives reduced total
      hydroxyproline and pepsin-resistant hydroxyproline content in comparison with
      that of the control (vehicle, UV-irradiation group). Moreover, naphthol AS-D
      chloroacetate esterase staining and diaminobenzidine staining suggested that
      leukocytes including neutrophils increased in the UV-exposed skin. In contrast,
      weak staining was observed in skin treated with xanthine derivatives. CONCLUSION:
      Topical application of plant extracts and xanthine derivatives suppressed wrinkle
      formation, dermal connective alteration, and collagen accumulation. It is
      suggested that xanthine derivatives prevented neutrophil infiltration caused by
      UV-irradiation.

PMID- 17523931
TI  - The effect of psoralen plus ultraviolet A in vitro in HUT-78 enhances by 5
      aminolevulinic acid.
AB  - BACKGROUND: Sezary syndrome and mycosis fungoides are forms of cutaneous T-cell
      lymphoma, and in the early stage of these diseases psoralen plus ultraviolet A
      (PUVA) is one of the treatments of choice. Photodynamic therapy using 5
      aminolevulinic acid (ALA-PDT) is an effective, non-invasive, and safe treatment
      for most superficial skin cancers. In order to obtain greater efficacy of PUVA,
      we investigated the synergistic anti-tumor effects of ALA-PDT and PUVA using 8
      methoxypsoralen (8-MOP) and a UVA lamp. METHODS: The in vitro effects of PUVA and
      ALA-PDT and their combination in HUT-78 cell line from human SS were determined
      by MTT assay. RESULTS: In our results, cell proliferation compared with controls
      was inhibited to 53.2% with UVA alone, 52.3% with 1 microM 8-MOP, 43.8% with 100
      microM ALA, and 19.2% with combined 8-MOP and ALA. CONCLUSION: Combined use of
      ALA and PUVA using 8-MOP and UVA lamps, which are widespread in Japan, had a
      strong anti-tumor effect in vitro. Combined treatment with ALA-PDT and PUVA using
      a UVA lamp appears to have a strong treatment effect.

PMID- 17523932
TI  - Lack of effect of oral selenite on p53 associated gene expression during TL01
      therapy of psoriasis patients.
AB  - Selenium (Se) has protective properties against ultraviolet (UV)-induced changes
      in skin cells in vitro but little is known about such activity in human subjects.
      In the present study, seven patients with psoriasis ingested 400 microg of sodium
      selenite daily during a 4 week course of whole-body narrow-band UVB (TL01)
      therapy while six more psoriasis patients, similarly irradiated, ingested a
      placebo. Skin biopsies, collected at the start and end of the phototherapy were
      analysed for phosphorylated p53, Fas, Bcl-2, Bax and oxidized guaninosine, and
      for numbers of Langerhans and sunburn cells. Following the TL01 therapy, no
      significant difference was observed for any of these markers when the Se group
      was compared with the placebo group of patients, although p53 and Bcl-2
      expression decreased in the Se supplemented group.

PMID- 17523933
TI  - Local narrowband UVB phototherapy vs. local PUVA in the treatment of chronic hand
      eczema: incorrect assertion of treatment equivalence.

PMID- 17523936
TI  - Use-dependent control of presynaptic calcium signalling at central synapses.
AB  - Voltage-gated Ca(2+) channels activated by action potentials evoke Ca(2+) entry
      into presynaptic terminals thus briefly distorting the resting Ca(2+)
      concentration. When this happens, a number of processes are initiated to re
      establish the Ca(2+) equilibrium. During the post-spike period, the increased
      Ca(2+) concentration could enhance the presynaptic Ca(2+) signalling. Some of the
      mechanisms contributing to presynaptic Ca(2+) dynamics involve endogenous Ca(2+)
      buffers, Ca(2+) stores, mitochondria, the sodium-calcium exchanger, extraterminal
      Ca(2+) depletion and presynaptic receptors. Additionally, subthreshold
      presynaptic depolarization has been proposed to have an effect on release of
      neurotransmitters through a mechanism involving changes in resting Ca(2+). Direct
      evidence for the role of any of these participants in shaping the presynaptic
      Ca(2+) dynamics comes from direct recordings of giant presynaptic terminals and
      from fluorescent Ca(2+) imaging of axonal boutons. Here, some of this evidence is
      presented and discussed.

PMID- 17523937
TI  - GFP imaging of live astrocytes: regional differences in the effects of ischaemia
      upon astrocytes.
AB  - The basic division between white matter 'fibrous' astrocytes and grey matter
      'protoplasmic' astrocytes is well established in terms of their morphological
      differences. The availability of transgenic animals with green fluorescent
      protein (GFP) expression restricted to specific glial cell types now provides an
      approach for looking at changes in cell number and morphology in the two
      astrocyte types in whole mount preparations. This is an important goal, as the
      ease of generating astrocyte cultures has led to a proliferation of studies that
      have examined ischaemic effects on astrocytes in vitro. This has in turn
      engendered a belief that astrocytes have an extraordinary resistance to ischaemic
      injury, a belief that runs counter to almost all the data available from in vivo
      and whole-mount preparations. One possible source of this confusion is the
      reactive changes that occur in astrocytes following injury, which include an
      increase in cell number that may obscure early astrocyte cell death and which has
      been reported to initiate within hours of an ischaemic event. However, we show
      here that neither white matter nor grey matter GFP(+) astrocytes exhibit any
      feature of reactive astrocytosis within a 180-min period of reperfusion following
      modelled ischaemia in neonatal whole-mount preparations. We also show that white
      matter astrocytes are much more sensitive to ischaemia-reperfusion injury than
      are grey matter astrocytes, a feature that may have high significance for
      developmental disorders of white matter tracts such as cerebral palsy.

PMID- 17523938
TI  - The asymmetry of avian egg-shape: an adaptation for reproduction on dry land.
AB  - The present study describes the biological meaning of the asymmetrical shape in
      avian reproduction using quail. During the incubation of eggs, water was
      gradually lost and the air chamber which appeared in between the inner and outer
      shell membranes at the blunt end expanded, so that the angle made by the long egg
      axis and the horizontal line increased, presumably because the centre of gravity
      of the egg contents moved toward the sharp end. The increase in angle occurred in
      both fertile and infertile eggs, suggesting that this phenomenon occurs
      irrespective of fertility and is due to the asymmetrical shape. The increase in
      the volume of the air chamber resulted in an increase in the area of the inner
      shell membrane at the chamber to satisfy the amount of gas exchange needed by the
      developing embryo for better hatching. We isolated a 300-kDa protein from the
      inner shell membrane. It was produced by cells in the luminal epithelium of the
      oviductal isthmus and was found in the cortex of the fibres of shell membranes
      and a lining surrounding the air chamber. The lining comprised a medial layer
      between the inner and outer shell membranes in uterine eggs. The asymmetrical
      ellipsoid produces the air chamber at the blunt end of the avian egg during its
      sojourn in the oviductal isthmus, to maintain the blunt end up after oviposition
      and to raise that end during incubation in a dry environment, leading to high
      hatchability.

PMID- 17523939
TI  - Rats exposed to cocaine during late gestation and early postnatal life show
      deficits in hippocampal pyramidal and granule cells in later life.
AB  - In humans, the offspring of maternal cocaine misusers are known to have subtle
      cognitive and motor impairments in later life. It was therefore hypothesized that
      such exposure in animals would also affect the morphological structure of the
      brain. This possibility was investigated by exposing rats to cocaine between
      embryonic day 15 and postnatal day 6. Samples of the cocaine-exposed and control
      rats were killed for examination at 22 and 150 postnatal days of age.
      Stereological procedures (the Cavalieri principle together with the physical
      disector method) were utilized to estimate the total number of pyramidal and
      granule cells in defined regions of the hippocampal formation. At 22 days of age,
      the control offspring had about 373 000 pyramidal cells whereas the cocaine
      treated animals only had about 310,000 cells in the CA1 + CA2 + CA3 region. By
      150 days of age the values were about 396,000 and 348,000, respectively. The
      differences between age-matched groups were statistically significant. There were
      about 626,000 and 687,000 dentate gyrus granule cells in the 22-day-old control
      and cocaine-treated groups, respectively. By postnatal day 150 the control rats
      had about 832,000 granule cells whilst the cocaine-treated rats had about
      693,000. There was a significant main effect of age as well as group-age
      interaction in this measure. These results show that even moderate exposure to
      cocaine during the late gestation and early postnatal period in rats is a potent
      teratogen and can markedly influence the development of neurons in the
      hippocampal formation.

PMID- 17523940
TI  - The double role of the endoplasmic reticulum chaperone tapasin in peptide
      optimization of HLA class I molecules.
AB  - During the assembly of the HLA class I molecules with peptides in the peptide
      loading complex, a series of transient interactions are made with ER-resident
      chaperones. These interactions culminate in the trafficking of the HLA class I
      molecules to the cell surface and presentation of peptides to CD8(+) T
      lymphocytes. Within the peptide-loading complex, the glycoprotein tapasin
      exhibits a relevant function. This immunoglobulin (Ig) superfamily member in the
      endoplasmic reticulum membrane tethers empty HLA class I molecules to the
      transporter associated with antigen-processing (TAP) proteins. This review will
      address the current concepts regarding the double role that tapasin plays in the
      peptide optimization and surface expression of the HLA class I molecules.

PMID- 17523941
TI  - Bone marrow dendritic cells internalize live RF-81 bovine rotavirus and rotavirus
      like particles (RF 2/6-GFP-VLP and RF 8*2/6/7-VLP) but are only activated by live
      bovine rotavirus.
AB  - Dendritic cells (DC) represent the link between innate and adaptive immunity.
      They are classified as antigen-presenting cells (APC) and can initiate and
      modulate the immune response. To investigate the interaction with DCs, live RF-81
      bovine rotavirus strain (RFV) and rotavirus-like particles (rota-VLP), RF 2/6-GFP
      VLP and rota RF 8*2/6/7-VLP, were added in vitro to murine bone marrow-derived
      DCs (bmDCs). Live RFV, RF 2/6-GFP-VLP and RF 8*2/6/7-VLP all bound to bmDC and
      were internalized but only live RFV stimulated phenotypic maturation of the bmDCs
      as shown by the upregulation of the co-stimulatory molecule CD86. Even though
      bmDCs internalized RF 2/6-GFP-VLP and RF 8*2/6/7-VLP as efficiently as live RFV,
      these rota-VLP were not able to activate the cells. Supernatants derived from
      bmDC cultures treated with live RFV, RF 2/6-GFP-VLP or RF 8*2/6/7-VLP were
      examined for TNF-alpha production. At 6, 18 and 24 h post-infection, TNF-alpha
      concentrations were significantly increased in cultures treated with live RFV and
      rota-VLP compared with untreated cultures. In conclusion, this study showed that
      live RF-81 bovine rotavirus strain was internalized and induced bmDCs activation,
      whereas both RF 2/6-GFP-VLP and RF 8*2/6/7-VLP were internalized by bmDCs without
      triggering their activation.

PMID- 17523942
TI  - Aiolos controls gene conversion and cell death in DT40 B cells.
AB  - The Ikaros family transcription factor Aiolos is important for B cell function,
      since B cells of Aiolos-null mutant mice exhibit an activated phenotype, enhanced
      B-cell receptor (BCR) signalling response and develop a systemic lupus
      erythematosus (SLE) type autoimmune disease. Aiolos has also been reported to
      interact with anti-apoptotic Bcl-2 and Bcl-x(L) in T cells, but whether Aiolos
      regulates cell death has not been studied in B cells. Here we show that the
      disruption of Aiolos in the DT40 B cell line induces a cell death sensitive
      phenotype, as the Aiolos(-/-) cells are more prone to apoptosis by nutritional
      stress, BCR cross-linking, UV- or gamma-irradiation. Furthermore, the Aiolos(-/-)
      cells have defective Ig gene conversion providing evidence that Aiolos is needed
      for the somatic diversification of the BCR repertoire. The re-expression of DNA
      binding isoform Aio-1 was able to restore the gene conversion defect of the
      Aiolos-deficient cells, whereas the introduction of dominant negative isofom Aio
      2 had no effect on gene conversion, thus demonstrating the functional importance
      of alternative splicing within Ikaros family. Although the Aiolos(-/-) cells
      exhibit reduced expression of activation-induced cytidine deaminase (AID),
      ectopic AID overexpression did not restore the gene conversion defect in the
      Aiolos(-/-) cells. Our findings indicate that Aiolos may regulate gene conversion
      in an AID independent manner.

PMID- 17523943
TI  - Human peripheral blood dendritic cells and monocyte subsets display similar
      chemokine receptor expression profiles with differential migratory responses.
AB  - Human antigen presenting cells (APC) found in peripheral blood are considered to
      be precursors that have been released from the bone marrow and are in transit to
      the peripheral tissues. These APC populations include myeloid dendritic cells
      (mDC), plasmacytoid DC (pDC) and monocytes (Mo). To assign specialized functional
      roles and stages of development for APCs, CD33 expressing APC subsets were
      examined for their capacity to respond to chemokines. Three major CD33(+) subsets
      including CD33(bright)CD14(bright) Mo, CD33(bright)CD14(-) CD11c(+) mDC and
      CD33(dim)CD14(-) pDC were present. Dendritic cells subsets and Mo expressed low
      levels of CC and CXC receptors, but distinctive chemokine receptor expression
      profiles were not observed. The percentage of cells expressing a particular
      chemokine receptor varied from donor to donor and over time in the same donor.
      Myeloid DC and Mo but not pDC migrated toward CXCL12 in a concentration dependent
      manner. Monocytes and pDC, but not myeloid DC, were attracted by high
      concentrations of CXCL10. All CD33(+) subsets migrated in a concentration
      dependent manner toward CCL19, but responded less robustly to CCL21. CCL20 was
      not chemoattractant for any population. Despite the finding that APC did not
      exhibit unique surface chemokine receptor expression patterns, they exhibited
      differential migration to CXCL12, CXCL10 and CCL21 but not to CCL20 or CCL19.

PMID- 17523944
TI  - Increased asymmetric dimethylarginine concentrations in stimulated peripheral
      blood mononuclear cells.
AB  - Elevated concentrations of total homocysteine as well as of asymmetric
      dimethylarginine (ADMA) in the blood have been reported to reflect an increased
      cardiovascular risk. ADMA is formed by endothelial cells and is an endogenous
      inhibitor of NO synthase. Earlier we have found that human peripheral blood
      mononuclear cells (PBMC) produce homocysteine upon stimulation with mitogens
      concanavalin A, phytohaemagglutinin and pokeweed mitogen. In this study, the
      ability of PBMC to form ADMA and symmetric dimethylarginine (SDMA) was
      determined. Effects were compared with levels of cysteine, homocysteine and
      arginine in cultures. Increased concentrations of ADMA and SDMA were found in
      mitogen-stimulated compared with unstimulated PBMC. Arginine and cysteine
      concentrations did not differ between stimulated and unstimulated PBMC. There
      existed significant associations between concentrations of homocysteine and ADMA
      (Spearman rank correlation (rs) = 0.575) as well as SDMA (rs = 0.436, both P <
      0.001). Treatment of stimulated PBMC with the anti-inflammatory compounds
      salicylic acid (5 mm) and atorvastatin (25 microm) decreased the rate of ADMA and
      SDMA formation. Results of these in vitro studies show that ADMA and SDMA
      formation coincides with homocysteine production in human PBMC. Activated PBMC
      not only release Th1-type cytokine gamma-interferon, which is the most important
      inducer of nitric oxide synthase, but also ADMA, a natural inhibitor of the
      enzyme.

PMID- 17523945
TI  - Histamine in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by a persistent
      inflammation of the synovium, leading to the erosion of articular cartilage and
      bone. Synovial mast cells and their effector molecule, histamine, receive
      increased attention as mediators of joint inflammation. The aim of our study was
      to analyse levels of free histamine in serum and joint fluid of RA patients and
      to evaluate the potential inflammatogenic properties of histamine in vivo and in
      vitro. Histamine levels were measured by an ELISA in synovial fluid and sera of
      RA patients and of healthy controls. Histamine levels were also assessed in
      plasma of RA patients undergoing anti-TNF-alpha treatment. In the murine part of
      the study, histamine was injected intra-articularly in the knee joint of mice and
      the joints were subsequently analysed with respect to induction of inflammation.
      RA patients displayed significantly lower levels of histamine in circulation
      (0.93 +/- 0.16 ng/ml) compared with the healthy controls (1.89 +/- 0.45 ng/ml, P
      < 0.001). Locally, in synovial fluid the levels of histamine were even lower
      (0.37 +/- 0.16 ng/ml, P < 0.0006). Long-term anti-TNF-alpha treatment
      significantly increased circulating levels of histamine in RA patients. Our
      experiments on animals show that histamine on its own neither induces
      inflammation in the joint cavity nor influences the course of HMGB1 and
      peptidoglycan-induced joint inflammation. Based on our experimental and clinical
      studies we suggest that histamine lacks harmful properties in RA.

PMID- 17523946
TI  - Modulatory effect of killed Propionibacterium acnes and its purified soluble
      polysaccharide on peritoneal exudate cells from C57Bl/6 mice: major NKT cell
      recruitment and increased cytotoxicity.
AB  - Propionibacterium acnes has been described as a potent adjuvant to immune
      responses in vitro and in vivo. Presently, we analysed the modulation of
      peritoneal exudate cells (PEC) by heat-killed P. acnes or its purified soluble
      polysaccharide (PS), both injected intraperitoneally in C57Bl/6 mice, aiming at
      their recruitment and cytotoxicity. Both treatments induced an increase in
      macrophages, immature dendritic cells, B1a lymphocytes and NK1.1(+) CD3(+) cells.
      The bacterium caused a remarkable increase in a NK1.1(+) CD3(+) CD4(-) CD8(-)
      cells subpopulation, whereas the PS component seemed responsible for the
      recruitment of mainly macrophage cells. To assess P. acnes and PS adjuvant effect
      on PEC cytotoxicity we evaluated their in vitro effect on murine B16F10 melanoma
      cells. The effector cells from the heat-killed bacteria and PS-treated groups
      lysed melanoma cells in co-cultures with PEC. Mice genetically deficient in IFN
      gamma, when stimulated with P. acnes or PS, had reduced PEC cytotoxicity, and the
      cytotoxic effect was completely abrogated in PEC from iNOS(-/-) mice. The
      tumoricidal activity of PEC from P. acnes-treated mice was mediated by
      macrophages and NKT cells stimulated with IL-12. In PS-treated mice the
      cytotoxicity was mediated mainly by macrophages. Moreover, both treatments
      increased IL-4 and IFN-gamma production by NKT cells. In conclusion, we show that
      P. acnes act mainly by recruiting and activating NKT double-negative cells in
      PEC, which were shown to be tumoricidal in vitro when induced by IL-12.
      Macrophages induced by both P. acnes and PS have their antitumour effect
      dependent on NO production.

PMID- 17523947
TI  - Biochip array-based analysis of plasma cytokines in HIV patients with
      immunological and virological discordance.
AB  - Assessment of cytokines in body fluids or cells provides important information in
      understanding the disease process and designing treatment strategies. Recent
      introduction of antibody-based protein arrays have provided investigators
      simultaneous and specific detection of multiple analytes in a single sample using
      minimum volumes. In this study, we used a biochip array system capable of
      measuring 12 cytokines and growth factors (IL-2, IL-4, IL-6, IL-8, IL-10, IL
      1alpha, IL-1beta, IFN-gamma, TNF-alpha, monocyte chemoattractant protein-1 (MCP
      1), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF))
      in HIV patients with immunological and virological discordance (discordant) to
      find out differences if any, in their plasma cytokine profiles when compared with
      concordant HIV-infected individuals. A sandwich chemiluminescent assay was
      performed with plasma specimens of 110 HIV patients (55 discordant, 55
      concordant) and 22 normal healthy individuals followed by enzyme-linked
      immunosorbent assay (ELISA) to the confirm levels of cytokines and growth factors
      that showed significant differences in the two groups. The discordant HIV
      patients showed significantly higher levels of plasma VEGF (P = 0.001) and EGF (P
      = 0.034) levels when compared with concordant patients. Overall, the patients
      showed significantly higher levels of TNF-alpha, MCP-1 and VEGF when compared
      with the normal healthy controls (P < 0.05). ELISA for VEGF (P < 0.001) and EGF
      (P = 0.004) confirmed the comparison obtained with biochip array, between the
      discordant and concordant patients. The results of cytokine quantitation by
      biochip array and ELISA confirmed that this technology is not only comparable but
      also has a good potential in the future applications involving measurement of
      multiple cytokines with limiting specimens.

PMID- 17523948
TI  - Fc-gamma receptor polymorphisms are not associated with autoimmune Addison's
      disease.
AB  - Polymorphisms in the low-affinity Fcgamma receptors (FcgammaR) modulate their
      capacity to bind IgG and the subsequent immune response. Different FcgammaR
      polymorphisms have been reported to be associated with susceptibility and
      severity of various autoimmune diseases. We wanted to investigate associations
      between FcgammaR polymorphisms and autoimmune primary adrenal failure (Addison's
      disease). We have genotyped 149 patients with Addison's disease and 89 healthy
      controls for common polymorphisms in the genes coding for FcgammaRIIa,
      FcgammaRIIIa and FcgammaRIIIb using polymerase chain reaction. Patients with
      Addison's disease and controls showed no differences in genotype distributions of
      FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb. The results indicate that different
      FcgammaR polymorphisms do not have an impact on immune responses involved in the
      development of autoimmune Addison's disease.

PMID- 17523949
TI  - Association of HLA genes with ankylosing spondylitis in Han population of eastern
      China.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory disorder with a
      multifactorial genetic basis. HLA-B27 was reported with the greatest
      susceptibility to AS but did not act alone. The aim of this study was to search
      for other gene(s) associated with AS independently of HLA-B27 using 13
      microsatellite markers spanning 1.5 Mb from locus TAP1 to HLA-Cw and a single
      nucleotide polymorphism marker within NFkappaBIL1 gene promoter. Genotyping for
      microsatellites was performed in 175 AS patients of eastern Chinese and 219
      ethnically matched healthy controls using polymerase chain reaction with
      fluorescence-labelled primers, whereas the SNP marker was genotyped by direct DNA
      sequencing. Allele as well as haplotype frequencies were compared between cases
      and controls, and a linkage disequilibrium analysis was performed to estimate the
      LD relationship between the candidate regions. The frequencies of alleles
      D6S2811*128, STR_MICA*A5.1 and D6S2672*109, as well as haplotypes D6S2811*128
      D6S2927*213-D6S2810*340, D6S2927* 221-D6S2810*350-MICA*A5.1, and D6S2810*350
      MICA*A5.1-D6S2800* 136 were significantly increased in B27-positive AS patients
      when compared with B27-positive controls. The results indicated that there may be
      other gene(s) within the HLA region, especially around locus HLA-B or HLA-Cw,
      with susceptibility to AS independently of HLA-B27.

PMID- 17523950
TI  - A dual altered peptide ligand inhibits myasthenia gravis associated responses by
      inducing phosphorylated extracellular-regulated kinase 1,2 that upregulates
      CD4+CD25+Foxp3+ cells.
AB  - Myasthenia gravis (MG) and its animal model experimental autoimmune MG (EAMG),
      are T-cell dependent, antibody-mediated autoimmune disorders. A dual altered
      peptide ligand (APL) composed of the tandemly arranged two single amino acids
      analogs of two myasthenogenic peptides, p195-212 and p259-271, was demonstrated
      to downregulate, in vitro and in vivo, MG-associated autoimmune responses.
      Upregulation of regulatory CD4(+)CD25(+) cells plays a key role in the mechanism
      of action of the dual APL. The objectives of the present study were to address
      the involvement of extracellular-regulated kinase (ERK)1,2 in the mechanisms by
      which the dual APL-induced CD4(+)CD25(+) cells suppress MG-associated autoimmune
      responses. We demonstrate here that administration of the dual APL increased
      activated ERK1,2 in the CD4(+)CD25(+)-enriched population. Further, inhibition of
      ERK1,2 by its inhibitor, U0126, in dual APL-induced CD4(+)CD25(+) cells,
      abrogated their ability to suppress interferon (IFN)-gamma secretion by lymph
      node (LN) cells of mice that were immunized with the myasthenogenic peptide.
      Moreover, inhibition of ERK1,2 in the dual APL-induced regulatory CD4(+)CD25(+)
      cells, resulted in downregulation of the forkhead box p3 (Foxp3) gene and protein
      expression levels, as well as in the downregulation of CD4(+)CD25(+) development,
      suggesting that the active suppression exerted by the dual APL via CD4(+)CD25(+)
      cells depends on ERK1,2 activity.

PMID- 17523951
TI  - Patterns of in vitro lymphoproliferative responses among HTLV-1-infected
      subjects: upregulation by HTLV-1 during HIV-1 co-infection.
AB  - The present study evaluated the in vitro response to different mitogens and a
      candidin antigen (CMA) in Human T-cell lymphotropic virus type 1 (HTLV-1) and co
      infected HIV-1/HTLV-1 patients, to identify if this co-infection may modify the
      spontaneous lymph proliferative response. Peripheral blood mononuclear cells from
      72 healthy seronegative controls, 75 asymptomatic HTLV-1-infected carriers, 42
      HAM/TSP cases, 33 solely HIV-1-infected subjects and 24 HIV-1/HTLV-1 patients
      were assayed in the presence and absence of mitogens (PHA, PWM and OKT3) and CMA.
      The HAM/TSP group had the highest proliferation rate at 3 and 6 days after
      culture. HAM/TSP cases showed decreased response to PHA, compared with
      asymptomatic HTLV-1 subjects, and most important, the co-infected HIV-1/HTLV-1
      cases presented a similar response to HTLV-1-infected subjects after 3 days of
      culture. The singles HIV-1-infected group had decreased in vitro response. It
      appears that during co-infection, the HTLV-1 regulatory proteins overwhelm the
      action of HIV-1 regulatory proteins.

PMID- 17523952
TI  - Generation of a considerable number of functional mast cells with a high basal
      level of FcepsilonRI expression from cord blood CD34+ cells by co-culturing them
      with bone marrow stromal cell line under serum-free conditions.
AB  - The number of mast cells (MC) that can be obtained from tissue is limited, making
      it difficult to study the role of MC. Cultured MC derived from cord blood (CB)
      CD34(+) cells proliferate well compared with those derived from adult CD34(+)
      cells; however, they have been reported to be phenotypically or functionally
      immature regardless of culture system. For example, very few cells express
      FcepsilonRI. To resolve this problem, we addressed the effect of human bone
      marrow stromal cell line on the development of cultured MC. CB-CD34(+) (1 x
      10(4)) cells were cultured for 8 weeks in a serum-free medium containing rhIL-6
      and rhSCF with or without a human bone marrow stromal cell line, namely, co
      culture and liquid culture, and were compared in various regards. MC were
      basically determined by metachromatic staining of granules. The number of MC
      obtained (60.3 +/- 15.8 x 10(5) versus 2.0 +/- 1.0 x 10(5)), percentage of
      FcepsilonRI(+) cells (29.3 +/- 9.4% versus 1.9 +/- 0.8%), histamine content (9.7
      +/- 2.8 pg/cell versus 5.8 +/- 2.3 pg/cell), and IgE-mediated histamine release
      (46 +/- 10% versus 17 +/- 7%) were higher (P < 0.01 and P < 0.05) in the co
      culture than in the liquid culture. When CB-CD34(+) cells were developed in
      liquid culture with the co-culture supernatant (CM), a significant increase (P <
      0.01) in the percentage of FcepsilonRI(+) cells and in cell number was observed
      but these values were lower than those of co-cultured MC. We concluded that this
      co-culture system was useful for obtaining a considerable number of mature MC
      with a high basal level of functional FcepsilonRI expression from CB-CD34(+)
      cells. Yet unknown humoral factors in CM may partly mediate this effect.

PMID- 17523954
TI  - Anti-oxidative/oxidative status of rat liver after ovariectomy.
AB  - The lack of protective action of oestrogens which appears during menopausal
      period may be the reason of serious metabolic disturbances including oxidative
      stress. The hypothesis was stated that ovariectomy may induce the variations of
      antioxidant/oxidant status which can be detected in rat liver. A total of 102
      healthy Wistar female rats were included in the experiment and divided into
      control (CON; n = 6), sham-operated (SHO; n = 48) and ovariectomized (OVX; n =
      48) groups. Animals from SHO (n = 6) and OVX (n = 6) groups were killed every
      week during 8 weeks of experiment to detect dynamic changes in examined
      parameters. Anti-oxidative enzyme activities [glutathione peroxidase (GSH-Px);
      superoxide dismutase (SOD)] as well as total antioxidant capacity (TAC) and the
      intensity of lipid peroxidation, measured by the concentration of N,N,diethyl-p
      phenylene diamine (DEPPD) radical, were determined in liver homogenates by the
      use of spectrophotometric methods. Wave-like patterns of examined parameters
      within 8 weeks of experiment were detected. GSH-Px activity tended to be higher
      in OVX animals and was significantly lower at 8th week when compared with 1st
      week of experiment. SOD activity was higher in SHO animals and showed significant
      differences between 3rd, 4th, 7th and 1st week. TAC values were significantly
      higher in OVX when compared with SHO groups in 2nd, 4th, 5th week and
      significantly lower in 3rd, 6th and 7th week of the experiment. The concentration
      of DEPPD radicals tended to increase in OVX group. In conclusion, ovariectomy
      which leads to oestrogen insufficiency is reflected as well in variation of anti
      oxidative/oxidative parameters in rat liver homogenates.

PMID- 17523955
TI  - Ultrastructural findings in porcine hearts after extracorporeal long-term
      preservation with a modified Langendorff perfusion system.
AB  - Preserved ultrastructure is an important precondition for functional regeneration
      after heart transplantation. We investigated the effectiveness of a newly
      developed modified Langendorff system in extracorporeal heart perfusion.
      (Experiment I) Cardioplegia and cold ischaemia were performed in six pigs. Hearts
      were connected to a modified Langendorff system, and perfused with leucocyte
      depleted autologous blood. (Experiment II) The untreated hearts of three healthy
      pigs served as controls. Forty-seven myocardial biopsies at different timepoints
      (I: n = 29, II: n = 18) were investigated by transmission electronmicroscopy.
      Cardioplegia/hypothermia (I) induced mild-to-moderate mitochondrial swelling,
      mild myofibrillar degeneration in cardiomyocytes and moderate endothelial oedema.
      After 4 h reperfusion cardiomyocytes showed moderate myofibrillar and mild
      sarcolemmal damage. Moderate endothelial degeneration, mild interstitial oedema
      and haemorrhages appeared. Untreated hearts (II) showed severely damaged
      mitochondria and nuclei after 30 min while the myofibrillar structure remained
      unaffected until 4 h later. This is a promising model for extracorporeal heart
      perfusion. However, ultrastructural findings indicated that some necessary
      modifications to prevent cellular damages during reperfusion were needed.

PMID- 17523956
TI  - Reference histology of veal calf genital and endocrine tissues - an update for
      screening on hormonal growth promoters.
AB  - An animal experiment has been performed with 42 veal calves, 21 males and 21
      females, which were fed and housed according to European regulations for veal
      calves. The animals were kept in six groups of seven animals and fed milk
      replacer supplemented with three different levels of lactulose (0%, 1% and 3%)
      and some roughage. At the start of the experiment the animals were 1-3 weeks of
      age and they were slaughtered at 26 weeks. From male animals prostate, bulbo
      urethal gland and testes were sampled, from female animals Bartholin's gland,
      uterus, cervix and ovaries were sampled. From all animals thyroid, thymus,
      adrenals, liver and kidneys were sampled. Histological investigation of the
      prostates and bulbo-urethral glands showed normal histology. This means that
      dilated tubules, strong secretion, increased mucinous glandular tissue and severe
      hyperplasia and squamous metaplasia, as is regularly observed in practice in the
      Netherlands, were not present in these animals. None of these prostates would be
      judged as positive in the screening for hormones as is performed by the Dutch
      Food and Consumer Product Safety Authority (VWA). The female calves also showed
      normal histology of Bartholin's gland except for three animals that appeared to
      be in oestrus and showed some metaplasie of the ducts but with a normal gland to
      duct ratio. These animals would be judged as suspect. The liver and kidney showed
      minor alterations due to slight infections during the experimental period. This
      experiment showed that it is possible to raise veal calves according to the
      practice without getting positive histology in the prostate or Bartholin's gland.

PMID- 17523957
TI  - Immunohistochemical expression of cyclooxygenase-2 in canine ovarian carcinomas.
AB  - Ovarian tumours among domestic animals are frequently encountered in bitch.
      Cyclooxygenase-2 (COX-2) expression has been evaluated in different kind of
      canine primary epithelial neoplasms. Eleven canine ovarian carcinomas and two
      normal samples were evaluated immunohistochemically for COX-2 expression. Nine of
      11 carcinoma samples (81%) expressed COX-2 enzyme isoform. The immunoreactivity
      was intracytoplasmically recorded and the intensity ranged from faint to strong.
      Our results show that COX-2 is expressed in canine ovarian carcinoma, suggesting
      a potential role of COX-2 in canine ovarian carcinogenesis.

PMID- 17523958
TI  - Adenocarcinoma metastasis of the intertransversarius cervicis muscle eliciting a
      right forelimb lameness in a dog.
AB  - This article describes identification of a metastatic adenocarcinoma to the
      intertransversarius cervicis muscle using magnetic resonance imaging (MRI) in a
      dog that presented with chronic lameness of the right forelimb. Magnetic
      resonance imaging revealed a right sided, ovoid signal abnormality within the
      intertransversarius cervicis muscle lateral to the sixth cervical (C6) vertebra.
      The lesion was uniform, hyperintense on T2- and isointense on T1-weighted images
      to muscle and exhibited uniform contrast enhancement on T1-weighted images. The
      MRI findings were consistent with a neoplasia. Surgical excision was performed.
      Histopathological diagnosis was metastatic fibrous adenocarcinoma. The dog
      recovered rapidly but 6 months post-operatively he was killed because of lung
      metastases. Necropsy was declined and the primary tumour could not be identified.

PMID- 17523959
TI  - Xylazine premedication does not modify the onset and duration of cisatracurium
      blockade in anaesthetized dogs.
AB  - The purpose of this study was to evaluate the effect of xylazine as premedication
      on the onset time and duration of cisatracurium neuromuscular blockade in
      anaesthetized dogs. This study was carried out on 12 healthy dogs aged 0.5-6
      years and weighing 9-26 kg undergoing various elective surgical procedures. The
      dogs were randomly divided into two groups of t (test) and c (control), with six
      dogs each. In group t, premedication was conducted using acepromazine maleate 0.3
      mg kg(-1) and xylazine 0.3 mg kg(-1) and in group c only acepromazine (same dose)
      was injected intramuscularly 20 min before general anaesthesia. After induction
      with thiopental, anaesthesia was maintained with halothane in oxygen to deliver
      an end-tidal halothane concentration of 1.1%. Neuromuscular blockade was induced
      with cisatracurium 0.2 mg kg(-1) and monitored using the train-of-four (TOF)
      stimulation pattern applied at the ulnar nerve. The onset time of cisatracurium
      blockade was 195 +/- 85.44 s in test and 153.3 +/- 38.16 s in control group. The
      duration of neuromuscular blockade was 24.8 +/- 4.79 min in t and 28.3 +/- 5.46
      min in the c group. Statistical analysis of the data showed no significant
      difference between groups in terms of onset and duration of neuromuscular
      blockade.

PMID- 17523960
TI  - Genotyping glycogen storage disease type II and type V in cattle reared in the
      Czech Republic.
AB  - Genotyping was carried out for glycogen storage disease type II and type V in
      seven cattle breeds. The analysis was carried out using the polymerase chain
      reaction/restriction fragment length polymorphism (PCR/RFLP) method. In the
      breeds analysed [Charolais, Czech Spotted (Czech Simmental), Belgian Blue,
      Limousine, Blonde d'Aquitaine, Aberdeen Angus, and Beef Simmental sires reared in
      the Czech Republic], the recessive allele was not found in the PYGM
      (phosphorylase glycogen, muscle) responsible for the glycogen storage disease
      type V. In the same panel, the recessive allele in exon 7, exon 9 and exon 13 of
      the GAA (glucosidase alpha, acid), causing the glycogen storage disease type II
      was not found. Therefore, we have not revealed the recessives outside previous
      reported breeds. The knowledge of the breed-specific occurrence of inherited
      disorders facilitates focusing and reduces the costs of detecting the
      heterozygous carriers of recessive inherited disorders.

PMID- 17523961
TI  - Haematology, blood chemistry and urine parameters of free-ranging plains
      viscachas (Lagostomus maximus) in Argentina determined by use of a portable blood
      analyser (i-STAT) and conventional laboratory methods.
AB  - Haematology, blood chemistry and urine values were determined for 44 adult free
      ranging plains viscachas (Lagostomus maximus; Rodentia, Chinchillidae) in their
      pampas habitat in central Argentina. The study animals were captured in the wild
      and anaesthetized with a ketamine-xylazine combination for physical examination
      and sampling. Blood was obtained by venipuncture of the saphenous vein. Results
      for many of the blood parameters fall within the reference ranges for pet
      chinchillas. Differentiation of white blood cells revealed a predominantly
      neutrophil count for plains viscachas, while chinchillas have predominantly
      lymphocytes. Mean values for blood urea nitrogen, creatinine, aspartate
      aminotransferase and sodium were higher than the upper limit of the reference
      range for pet chinchillas. The results of seven analytes (haematocrit,
      haemoglobin, glucose, blood urea nitrogen, sodium, potassium, chloride) were
      compared by using both a portable blood analyser (i-STAT) in the field and
      conventional laboratory methods. In general, correlation and agreement between
      the two methods were low for most parameters.

PMID- 17523962
TI  - Comparative frequency of osseous macroscopic pathology and first report of gout
      in captive and wild-caught ratites.
AB  - This systematic survey of museum ratite (Pterocnemia, Rhea, Casuarius, Struthio,
      Dromias and Apteryx) skeletal collections was performed to reevaluate previous
      perspectives and assess effect of captivity on macroscopically detectable
      pathology. Trauma-related pathology (e.g. focal periosteal reaction, malformed
      vertebrae) was significantly more common in captive birds (chi2 = 13.414, P <
      0.0001) with variable timing of the different injuries. Pathology unrelated to
      trauma was equally represented in captive and wild-caught ratites. The latter
      included osteophytes of osteoarthritis, osteochondritis dissecans, infectious
      arthritis, gout (reported for the first time in a ratite) and neoplasia.

PMID- 17523963
TI  - Recurrent uveitis in horses: vitreal examinations with ultrastructural detection
      of leptospires.
AB  - This study documents the examination of 17 horses (both sexes, 3-18 years old)
      suffering from spontaneous equine recurrent uveitis (ERU). Vitreal samples
      obtained by pars plana vitrectomy were examined macroscopically and
      ultrastructurally, and in most cases also by cultural examination, by microscopic
      agglutination test (MAT) and by polymerase chain reaction. In 24% (4/17) of the
      animals, ultrastructural examination by electron microscopy revealed intact
      leptospiral bacteria in the vitreous. The leptospires were detected freely in the
      vitreous and also incorporated by a phagocyte. They were surrounded by a rim of
      proteinaceous material which was reduced around a phagocytosed leptospira. Ninety
      four per cent (16/17) of the vitreal samples presented significant antibody
      levels in the MAT, mostly against leptospiral serovar Grippotyphosa. Seventy-five
      per cent (9/12) of bacterial culture examinations were positive for leptospira.
      Polymerase chain reaction was positive in all (16/16) examinations performed. Our
      findings support previous reports suggesting that leptospires play an important
      role in the pathogenesis of ERU. Interestingly, this study found leptospires
      after secondary and later acute episodes. A persistent leptospiral infection is
      therefore suggested as the cause of ERU.

PMID- 17523964
TI  - Molecular and serological evidence for Anaplasma platys and Babesia sp. infection
      in a dog, imported in Belgium, from Southern Spain.
AB  - This case report describes a dog suffering from a co-infection with Babesia and
      Anaplasma parasites. Anaplasma platys was found to be responsible for the
      anaplasmosis by molecular biology techniques, while microscopical and serological
      evidence was found for a coexistent babesiosis, although this could not be
      confirmed by polymerase chain reaction. Moreover, the possible risk of import of
      exotic pathogens is highlighted.

PMID- 17523966
TI  - Assessing vascular risk in people with Type 1 diabetes.

PMID- 17523967
TI  - Quality assurance for diabetic retinal screening.

PMID- 17523968
TI  - The Pharmacy Diabetes Care Program: assessment of a community pharmacy diabetes
      service model in Australia.
AB  - AIM: To assess the impact of a community pharmacy diabetes service model on
      patient outcomes in Type 2 diabetes. METHODS: The study utilized a multisite,
      control vs. intervention, repeated-measures design within four states in
      Australia. Fifty-six community pharmacies, 28 intervention and 28 control, were
      randomly selected from a representative sample of urban and rural areas.
      Intervention pharmacies delivered a diabetes service to patients with Type 2
      diabetes, which comprised an ongoing cycle of assessment, management and review,
      provided at regular intervals over 6 months in the pharmacy. These services
      included support for self monitoring of blood glucose, education, adherence
      support, and reminders of checks for diabetes complications. Control pharmacists
      assessed patients at 0 and 6 months and delivered no intervention. RESULTS: A
      total of 289 subjects (149 intervention and 140 control) completed the study. For
      the intervention subjects, the mean blood glucose level decreased over the 6
      month study from 9.4 to 8.5 mmol/l (P < 0.01). Furthermore, significantly greater
      improvements in glycaemic control were seen in the intervention group compared
      with the control: the mean reduction in HbA(1c) in the intervention group was 
      0.97% (95% CI: -0.8, -1.14) compared with -0.27% (95% CI: -0.15, -0.39) in the
      control group. Improvements were also seen in blood pressure control and quality
      of life in the intervention group. CONCLUSION: A pharmacy diabetes service model
      resulted in significant improvements in clinical and humanistic outcomes. Thus,
      community pharmacists can contribute significantly to improving care and health
      outcomes for patients with Type 2 diabetes. Future research should focus on
      clarifying the most effective elements of the service model.

PMID- 17523969
TI  - Issues regarding quality assurance in the English National Screening Programme
      for Sight-threatening Diabetic Retinopathy: response to paper by C. Arun et al.,
      'Establishing ongoing quality assurance in a retinal screening programme'.

PMID- 17523971
TI  - Sounding the trumpet: the importance of research dissemination in alcohol policy.

PMID- 17523972
TI  - AA's first European experience and the spiritual experience of AA.

PMID- 17523973
TI  - A 21st-century Lazarus: the role of safer injection sites in harm reduction and
      recovery.

PMID- 17523980
TI  - The spatial ecology of alcohol problems: niche theory and assortative drinking.
AB  - AIMS: This paper summarizes several theoretical perspectives that serve to
      explain observed associations between concentrations of alcohol outlets and
      alcohol-related problems. A critique of each perspective discusses how each
      addresses the social etiology of these problems; that is, how, where and why
      these problems arise in association with alcohol outlets? METHODS: This
      theoretical work is based upon mathematical and computational models of the
      ecology of alcohol-related problems developed in the 'Ecosystems Modeling
      Project', an advanced research project of the National Institute on Alcohol Abuse
      and Alcoholism, United States. RESULTS: Associations between outlets and problems
      are thought to arise from the concentration of individuals in drinking places
      ('flow models'), the attraction of some places for people at risk for problems
      ('gravity models'), or because outlets are located in high-risk neighborhoods and
      have negative social normative effects ('social contextual models'). None of
      these approaches explain how some outlets come to have more problems than others
      (e.g. violent outlets). An alternative social ecological model is introduced
      which asserts that the complementary processes of niche marketing and assortative
      drinking form the social dynamic that explains these relationships. Alcohol
      sellers 'niche market' to select social strata, drinkers return to establishments
      at which they find people like themselves, and consequent social stratification
      of the market-place increases the levels of related problems in some outlets.
      CONCLUSIONS: The proposed mechanism is very general, and suggests that over
      concentrations of outlets will lead to stratification of drinking groups and
      intensification of problems related to those outlets.

PMID- 17523974
TI  - A vision of the next generation of behavioral therapies research in the
      addictions.
AB  - Whither, or wither, empirically supported therapies? Increasingly rigorous
      research in behavioral therapies has yielded a large number of effective
      therapies, but comparatively little work, demonstrating that integrating
      empirically supported therapies (ESTs) into standard practice results in
      meaningful improvements in patient outcomes. Methodology and strategies for
      evaluating ESTs and their effectiveness in clinical practice is a fairly recent
      innovation, and a host of unanswered questions remain regarding issues such as
      selection among different ESTs and what type of ESTs should be emphasized in
      dissemination efforts, what type of clinicians should be trained in what type of
      ESTs, the most effective training strategies for various types of clinicians, the
      need for ongoing supervision to maintain minimum levels of treatment fidelity and
      skill. In this review, we call for broader use of new research strategies and
      methods relevant to dissemination of ESTs; these may include adaptive designs,
      identification of mechanisms of action to foster greater emphasis on effective
      change principles, training and adoption trials, as well as novel implementation
      strategies including computer-assisted therapy and computer-assisted training.

PMID- 17523981
TI  - Alcoholics Anonymous in Ireland: AA's first European experience.
AB  - AIMS: To trace the evolution of Alcoholics Anonymous in Ireland from its
      establishment there in 1946, focusing on the efforts of early members to
      publicize the fellowship and negotiate a role for themselves in relation to
      existing religious and healthcare institutions. METHODS: Archival research,
      drawing mainly on primary sources in AA archives in New York and Dublin. RESULTS:
      Anticipated tensions between this fellowship, which had its roots in Evangelical
      Protestantism, and the politically powerful Roman Catholic Church in Ireland were
      skillfully avoided; initial hostility from the medical profession quickly
      dissipated; and AA distanced itself from policy debate on the wider topic of
      alcoholism as disease. CONCLUSIONS: The relatively smooth introduction of AA to
      Ireland, the first European country in which it was established, may be
      attributed to the essentially pragmatic nature of the fellowship and the
      strategic abilities of its early members.

PMID- 17523982
TI  - Conversation with Raphael Mechoulam.

PMID- 17523983
TI  - Genetic and environmental influences on the relationship between peer alcohol use
      and own alcohol use in adolescents.
AB  - AIMS: Genetically influenced aspects of adolescent behaviour can play a role in
      alcohol use and peer affiliation. We explored the correlations between friends'
      alcohol use and adolescent own use with a genetically sensitive design. DESIGN:
      Genetic and environmental factors were estimated on adolescent reports of their
      friends' alcohol use and their own use and problem use of alcohol. The
      correlations between the genetic and environmental factors that influence
      friends' alcohol use and adolescent own alcohol use and problem use were also
      estimated. PARTICIPANTS: A total of 862 twin pairs aged 11-17 years sampled from
      the UK population-based Cardiff Study of All Wales and North-west of England
      Twins (CaStANET). MEASUREMENTS: Data on adolescent own alcohol use and problem
      use and the alcohol use of their three best friends were obtained using self
      report questionnaires. FINDINGS: A significant genetic influence was found on
      adolescent friends' alcohol use (about 30%). Significant correlations of 0.60 and
      0.70 were found between the genetic influences on friends' alcohol use and
      adolescents' own use and problem use of alcohol. Common environmental influences
      were almost completely correlated for friends' alcohol use and adolescents' own
      alcohol use and problem use (0.91 and 0.94). CONCLUSIONS: There is considerable
      overlap in the common environmental and genetic factors that contribute to the
      relationship between adolescents' own alcohol use and that of their friends.
      These findings contribute to understanding of the mechanisms by which friends'
      alcohol use influences adolescent drinking behaviour.

PMID- 17523984
TI  - Stability of subtypes of natural recovery from alcohol dependence after two
      years.
AB  - AIMS: The lack of consistent findings in studies on natural recovery from alcohol
      dependence may reflect heterogeneous subgroups according to social support and
      problem severity. In a previous report, we identified the following groups: high
      severity of dependence, low alcohol-related problems and low social support (low
      problems-low support: LPLS), high severity of dependence, high alcohol-related
      problems and medium social support (high problems-medium support: HPMS) and high
      social support, late age of onset, low severity of dependence and low alcohol
      related problems (low problems-high support: LPHS). However, little is known
      about the trajectories of these groups. The aim of the present study is to
      analyse the stability of these three groups report on longer-term outcomes.
      DESIGN AND PARTICIPANTS: A cohort of initially untreated remitters recruited
      through media solicitation (n = 178) was followed-up after 24 months.
      MEASUREMENTS: Personal interviews using standardized instruments including social
      support together with interview data from collaterals. RESULTS: Differences
      between the cluster groups in social support diminished over time; however, even
      at follow-up, LPLS revealed less social support by friends when compared to LPHS
      and showed significant higher rates of relapse and utilization of formal help
      than did HPHS and LPHS. CONCLUSIONS: Data show that the interplay between
      psychosocial resources and substance-related problems may still account for
      differences in trajectories of naturally remitted individuals in a 2-year follow
      up.

PMID- 17523985
TI  - Cognitive impairment in Aboriginal people with heavy episodic patterns of alcohol
      use.
AB  - BACKGROUND: With chronic alcohol abuse, cognitive studies suggest that
      progressive cognitive decline may precede more serious and irreversible
      neurological syndromes. The early detection of cognitive impairment may therefore
      aid in the prevention of permanent brain damage. Despite the devastating
      consequences of alcohol abuse among Aboriginal Australians, the effects on brain
      function have never been studied in this population and a lack of appropriate
      assessment tools has prevented the development of such research. AIMS: To
      determine the impact of long-term and heavy episodic alcohol use on cognitive
      function in Aboriginal people. DESIGN: Cross-sectional comparing heavy episodic
      alcohol users with non-alcohol users. SETTING: Two remote Aboriginal communities
      in north-east Arnhem Land, northern Australia. SUBJECTS: The control group
      consisted of 24 non-drinkers (15 males, nine female) and the heavy episodic group
      consisted of 20 people (19 males, one female) who had been drinking alcohol in a
      heavy episodic style (median 14 drinks per occasion) for a mean of 8.9 years (SD
      = 5.0). MEASUREMENTS: Interview to obtain demographic information, substance
      abuse history and symptoms of mental health and wellbeing, together with a
      computerized cognitive assessment battery (CogState Ltd). FINDINGS: Compared with
      non-drinkers, heavy episodic drinkers showed reduced psychomotor speed (P = 0.04)
      and reduced accuracy when performing tasks of attention (P = 0.045), working
      memory (P = 0.04), implicit memory (P = 0.03) and associate learning and memory
      (P = 0.001). CONCLUSIONS: Specific cognitive abnormalities that suggest
      frontostriatal abnormalities and have been observed in association with chronic
      alcoholism in other populations were observed among Aboriginal Australians who
      were heavy episodic alcoholic users.

PMID- 17523986
TI  - Rate of detoxification service use and its impact among a cohort of supervised
      injecting facility users.
AB  - BACKGROUND: Vancouver, Canada recently opened a medically supervised injecting
      facility (SIF) where injection drug users (IDU) can inject pre-obtained illicit
      drugs. Critics suggest that the facility does not help IDU to reduce their drug
      use. METHODS: We conducted retrospective and prospective database linkages with
      residential detoxification facilities and used generalized estimating equation
      (GEE) methods to examine the rate of detoxification service use among SIF
      participants in the year before versus the year after the SIF opened. In
      secondary analyses, we used Cox regression to examine if having been enrolled in
      detoxification was associated with enrolling in methadone or other forms of
      addiction treatment. We also evaluated the impact of detoxification use on the
      frequency of SIF use. RESULTS: Among 1031 IDU, there was a statistically
      significant increase in the uptake of detoxification services the year after the
      SIF opened. [odds ratio: 1.32 (95% CI, 1.11-1.58); P = 0.002]. In turn,
      detoxification was associated independently with elevated rates of methadone
      initiation [relative hazard = 1.56 (95% CI, 1.04-2.34); P = 0.031] and elevated
      initiation of other addiction treatment [relative hazard = 3.73 (95% CI, 2.57
      5.39); P < 0.001]. Use of the SIF declined when the rate of SIF use in the month
      before enrolment into detoxification was compared to the rate of SIF use in the
      month after discharge (24 visits versus 19 visits; P = 0.002). CONCLUSIONS: The
      SIF's opening was associated independently with a 30% increase in detoxification
      service use, and this behaviour was associated with increased rates of long-term
      addiction treatment initiation and reduced injecting at the SIF.

PMID- 17523987
TI  - Factor and item-response analysis DSM-IV criteria for abuse of and dependence on
      cannabis, cocaine, hallucinogens, sedatives, stimulants and opioids.
AB  - AIMS: This paper explored, in a population-based sample of males, the factorial
      structure of criteria for substance abuse and dependence, and compared
      qualitatively the performance of these criteria across drug categories using item
      response theory (IRT). DESIGN: Marginal maximum likelihood was used to explore
      the factor structure of criteria within drug classes, and a two-parameter IRT
      model was used to determine how the difficulty and discrimination of individual
      criteria differ across drug classes. PARTICIPANTS: A total of 4234 males born
      from 1940 to 1974 from the population-based Virginia Twin Registry were
      approached to participate. MEASUREMENTS: DSM-IV drug use, abuse and dependence
      criteria for cannabis, sedatives, stimulants, cocaine and opiates. FINDINGS: For
      each drug class, the pattern of endorsement of individual criteria for abuse and
      dependence, conditioned on initiation and use, could be best explained by a
      single factor. There were large differences in individual item performance across
      substances in terms of item difficulty and discrimination. Cocaine users were
      more likely to have encountered legal, social, physical and psychological
      consequences. CONCLUSIONS: The DSM-IV abuse and dependence criteria, within each
      drug class, are not distinct but best described in terms of a single underlying
      continuum of risk. Because individual criteria performed very differently across
      substances in IRT analyses, the assumption that these items are measuring
      equivalent levels of severity or liability with the same discrimination across
      different substances is unsustainable. Compared to other drugs, cocaine usage is
      associated with more detrimental effects and negative consequences, whereas the
      effects of cannabis and hallucinogens appear to be less harmful. Implications for
      other drug classes are discussed.

PMID- 17523988
TI  - Combined immunomodulating properties of 3,4-methylenedioxymethamphetamine (MDMA)
      and cannabis in humans.
AB  - AIMS: Cell-mediated immune function and the occurrence of mild infectious
      diseases was investigated. Participants Polydrug consumers of 3,4
      methylenedioxymethamphetamine (MDMA) and cannabis (n = 37) compared to cannabis
      users only (n = 23) and control group (n = 34). DESIGN: A longitudinal
      prospective study with three cross-sectional evaluations at time 0 and at 6
      months and 1 year was performed. FINDINGS: At baseline, a significant decrease in
      interleukin (IL)-2 and an increase in anti-inflammatory transforming growth
      factor (TGF)-beta1, together with a decrease in the number of total lymphocytes,
      CD4 and natural killer (NK) cells were observed in the MDMA-cannabis group, with
      intermediate alterations in the cannabis group. Immune alterations observed at
      baseline were sustained over time. No differences were found between regular and
      occasional MDMA users. A significantly higher rate of mild infections in regular
      MDMA-cannabis users compared with occasional MDMA-cannabis users and the
      remaining groups was observed. CONCLUSIONS: The present data confirm that long
      term alterations in immunological homeostasis may result in general health status
      impairment and subsequent increased susceptibility to infection and immune
      related disorders.

PMID- 17523989
TI  - Implicit learning, executive function and hedonic activity in chronic polydrug
      abusers, currently abstinent polydrug abusers and controls.
AB  - AIMS: The study seeks to evaluate impairments of implicit learning and executive
      function in chronic polydrug abusers. It was hypothesized that implicit learning
      and executive function correlate with anhedonia. DESIGN: A cross-sectional group
      comparison. SETTINGS: Department of Psychiatry, University of Tubingen, Germany.
      Participants A total of 25 male polydrug abusers with opiate dependence, n = 26
      polydrug abusers abstinent for more than 3 months and n = 26 non-drug-using
      healthy males. SETTING: Abstinent polydrug abusers were recruited from a
      community treatment centre, current polydrug abusers from local drug counselling
      services and controls through advertisements. MEASUREMENTS: A psychological
      battery assessing implicit learning (serial reaction-time task), various
      executive functions (latent inhibition, delayed matching-to-sample, Trail Making
      Test, acquisition and modification of conditioned responses, figural reasoning)
      and verbal logic memory was administered. Hedonic thoughts and activities as well
      as depressive symptoms were assessed through questionnaires. FINDINGS: In chronic
      polydrug abusers, there were moderate impairments of implicit learning, of
      acquisition, reversal and extinction of conditioned responses, of latent
      inhibition as well as anhedonia, while working memory was spared. In the
      abstinent group, cognitive performance was normal except for latent inhibition
      and more anhedonia and depression than in controls. CONCLUSIONS: The findings
      suggest that current polydrug abusers suffer from impairment of many cognitive
      functions and from anhedonia. During abstinence, there is near normal cognitive
      function but still anhedonia. Anhedonia was correlated with implicit learning but
      not with executive function.

PMID- 17523990
TI  - The Marijuana Check-up: promoting change in ambivalent marijuana users.
AB  - AIMS: To evaluate the efficacy of a two-session assessment and feedback
      intervention designed to reach and increase motivation for change in marijuana
      users who were experiencing negative consequences but were ambivalent about
      change. DESIGN: Random assignment to one of two types of feedback conditions or a
      delayed feedback control (DFC) with follow-up assessments at 7 weeks, 6 months
      and 12 months. Setting University of Washington research center in Seattle,
      Washington. PARTICIPANTS: A total of 188 adult male and female marijuana users
      who responded to advertisements. Interventions A personalized feedback (PF)
      condition utilizing motivational interviewing was compared to an educational
      control condition labeled multi-media feedback (MMF). MEASUREMENTS: Marijuana
      use, dependence symptoms, other associated negative consequences and motivational
      constructs were assessed at all time-points. FINDINGS: PF participants reported
      fewer days of use per week, fewer periods of use per day and fewer dependence
      symptoms at 7 weeks than those in the MMF and DFC conditions. PF participants
      also reported fewer days of use per week compared to MMF participants at the 12
      month follow-up and fewer dependence symptoms at both the 6- and 12-month follow
      ups compared to MMF participants. CONCLUSIONS: The PF intervention, delivered in
      the context of a check-up, shows potential as a way of reaching and motivating
      change in marijuana users with a diagnosable disorder who otherwise are not ready
      to approach treatment. Ways of augmenting the modest absolute levels of change
      are discussed.

PMID- 17523991
TI  - Equity of access to treatment, and barriers to treatment for illicit drug use in
      Australia.
AB  - AIMS AND DESIGN: This study investigated equity of access to treatment and
      barriers to treatment for illicit drug use, using Andersen's behavioural model of
      health service utilization. SETTING AND PARTICIPANTS: The study involved 492 drug
      users who had received treatment and 193 who had not. MEASUREMENTS: Participants
      were interviewed to gather data relating to 19 predisposing, need and enabling
      variables. FINDINGS: Never-treated participants exhibited less need for treatment
      than those who had received treatment. They experienced less negative emotion,
      used their main drug less often, had fewer drug-related health problems and fewer
      drug-using friends, were less likely to have blood-borne virus infections and
      were more likely to be using drugs for 'fun'. They also had more negative
      attitudes towards drug treatment staff, were less likely to believe that
      appropriate treatment was available and less likely to believe that professional
      help was necessary to get off drugs. Prevalence of physical and mental health
      problems was high in both groups. CONCLUSIONS: The study documented significant
      unmet treatment need and identified several sources of inequity and barriers to
      treatment that would be amenable to policy and service development. Drug user
      organizations and peer educators and motivational interventions in primary care
      settings should be utilized to market the nature and benefits of treatment
      effectively, and to address the causes of drug users' negative attitudes towards
      treatment.

PMID- 17523992
TI  - Factors associated with pathological gambling at 10-year follow-up in a national
      sample of middle-aged men.
AB  - BACKGROUND: The present analyses will expand on previous reports by considering
      the impact of eight psychiatric disorders and genetic vulnerability to problem
      (P) and pathological gambling gambling (PG). methods: Diagnoses of DSM-III-R life
      time P and PG were derived in 1992 and past-year P and PG in 2002 from 1675
      individual twins from the Vietnam Era Twin Registry. Logistic regression was used
      to predict past-year P and PG as a function of socio-demographics and life-time
      co-occurring psychiatric disorders including gambling problems measured in 1992.
      Co-twin analyses accounted for familial contributions to past-year gambling
      problems. RESULTS: High school or greater educational attainment was associated
      with less likelihood of current P and PG. With the exception of alcohol
      dependence and generalized anxiety/panic, all disorders studied remained
      associated significantly with an increase risk of past-year P and PG after
      adjusting for 1992 gambling symptoms. Past-year P and PG was associated
      significantly with the number of pathological gambling symptoms reported in 1992.
      After controlling for genetic and family environmental factors, one or more 1992
      symptoms were associated with 2002 symptoms. CONCLUSIONS: Education and substance
      dependence, mood and antisocial personality disorders were associated with
      current gambling. A history of PG symptoms is the strongest predictor of past
      year problem gambling.

PMID- 17523993
TI  - The impact of strategic funding by the tobacco industry of medical expert
      witnesses appearing for the defence in the Aho Finnish product liability case.
AB  - AIMS: To identify and evaluate tobacco industry strategies to recruit medical
      expert witnesses. METHODS: A systematic search was made of internal tobacco
      industry documents available on the Internet and at British American Tobacco
      Guildford Depository. Litigation by a plaintiff with laryngeal cancer against the
      tobacco industry in Finland was used as a case study of tobacco industry
      strategies to manipulate science and its use and deployment in defending a
      product liability claim. RESULTS: Thirty-three of 45 medical expert witnesses for
      the defence received research funding before or after testifying. One strategy
      was to employ those scientists as witnesses with whom the industry had worked
      since the 1960s. The older witnesses testified to the existence of a controversy
      which they had, in fact, helped to create. Those appearing in Helsinki District
      court apparently downplayed the importance of their involvement with the
      industry. Another strategy was the use of research funding to establish contacts
      with new potential witnesses, to strengthen existing contacts or to pay back
      helpful experts. CONCLUSIONS: The tobacco industry funded the majority of expert
      witnesses appearing for it, beyond simple recompense for the time involved. This
      may have unconsciously influenced the testimony given by the witnesses. This
      funding should be considered in court, but links between experts and the industry
      were often downplayed or, in some cases, the financial ties were being forged at
      the time and were not revealed. It would be helpful to establish norms to guide
      courts to understand the influences exerted by the tobacco industry in the
      preparation of cases requiring expert evidence.

PMID- 17523994
TI  - Acute effects of a guided relaxation routine (body scan) on tobacco withdrawal
      symptoms and cravings in abstinent smokers.
AB  - AIMS: To examine the acute effects of a guided relaxation routine (body scan) on
      desire to smoke and tobacco withdrawal symptoms in overnight abstinent smokers.
      DESIGN: Experimental. PARTICIPANTS: Thirty individuals reporting to smoke 10 or
      more cigarettes daily for at least 3 years. INTERVENTION: Participants were
      assigned randomly to complete a 10-minute body scan (experimental group n = 15)
      or listen to a natural history passage for 10 minutes (control group n = 15).
      MEASUREMENT: Ratings of strength of desire to smoke and smoking withdrawal
      symptoms were assessed at baseline, immediately after the interventions, and 5,
      10 and 15 minutes post-intervention. FINDINGS: There was a significant group x
      time interaction for strength of desire to smoke. The mean desire to smoke rating
      was significantly lower in the body scan group relative to the control group
      immediately after the intervention, and 5 minutes post-intervention. The body
      scan group also reported lower ratings of irritability, tension and restlessness,
      relative to the controls. CONCLUSION: A brief body scan intervention reduces
      strength of desire to smoke and some tobacco withdrawal symptoms in temporarily
      abstaining smokers. The body scan may be beneficial as a technique for managing
      cigarette cravings and withdrawal.

PMID- 17523995
TI  - Effectiveness of individually tailored smoking cessation advice letters as an
      adjunct to telephone counselling and generic self-help materials: randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of individually tailored smoking
      cessation advice letters as an adjunct to telephone counselling and generic self
      help materials. DESIGN: Randomized controlled trial. SETTING: The UK Quitline.
      PARTICIPANTS: A total of 1508 current smokers and recent ex-smokers.
      INTERVENTIONS: The control group received usual care (telephone counselling and
      an information pack sent through the post). The intervention group received in
      addition a computer-generated individually tailored advice letter. MAIN OUTCOME
      MEASURES: All outcomes were assessed at 6-month follow-up. The primary outcome
      measure was self-reported prolonged abstinence for at least 3 months. Secondary
      outcomes were self-reported prolonged abstinence for at least 1 month and 7-day
      and 24-hour point-prevalence abstinence. RESULTS: For the sample as a whole, quit
      rates did not differ significantly between the two conditions. However, among the
      majority (n = 1164) who were smokers at baseline, quit rates were consistently
      higher in the intervention group: prolonged abstinence for 3 months, 12.2% versus
      9.0% [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 0.96-2.04, P =
      0.080); prolonged abstinence for 1 month, 16.4% versus 11.3% (OR = 1.53, 95% CI =
      1.09-2.15, P = 0.013); 7-day point-prevalence abstinence, 18.9% versus 12.7% (OR
      = 1.59, 95% CI = 1.15-2.19, P = 0.004); 24-hour point-prevalence abstinence,
      20.9% versus 15.4% (OR = 1.45, 95% CI = 1.07-1.96, P = 0.015). CONCLUSIONS: The
      results for the smokers are encouraging in showing a small but useful effect of
      the tailored letter on quit rate. Versions of the tailoring program could be used
      on the web and in general practices, pharmacies and primary care trusts.

PMID- 17523996
TI  - SASSI: a reply to the critique of Feldstein & Miller (2007).

PMID- 17524003
TI  - International Patient Decision Aid Standards (IPDAS): beyond decision aids to
      usual design of patient education materials.

PMID- 17524004
TI  - A bird can't fly on one wing: patient views on waiting for hip and knee
      replacement surgery.
AB  - OBJECTIVES: To obtain patients' perspectives on acceptable waiting times for hip
      or knee replacement surgery. METHODS: A questionnaire with both open- and close
      ended items was mailed to 432 consecutive patients who had hip or knee
      replacement surgery 3-12 months previously in Saskatchewan, Canada. A content
      analysis was used to analyse the text data from the open-ended questions.
      RESULTS: The sample of 303 (response rate 70%) was 59% female with a mean age of
      70 years (SD 11). The median waiting time from the decision date to surgery was
      17 weeks. Individuals who rated their waiting time very acceptable (48%) had a
      median waiting time of 13 weeks compared with a median waiting time of 22 weeks
      for those who rated it unacceptable (23%). The two most common determinants of
      acceptability were patient expectations and pain and its impact on patient
      quality of life. The median maximum acceptable waiting time was 13 weeks and
      median ideal waiting time, 8.6 weeks. Seventy-nine per cent felt that those in
      greater need (higher severity) should go before them on the waiting list. Patient
      ratings of maximum acceptable waiting time were based on: pain and loss of
      mobility, time needed to prepare for surgery, and severity at the time of seeing
      the surgeon. In consideration of changing their surgeon to one with a shorter
      waiting list, 68% would not. CONCLUSIONS: Patient views on waiting times are not
      only related to quality of life issues, but also to prior expectations and
      notions of fairness and priority. Understanding patient views on waiting for
      surgery has implications for better management of waiting times and experiences
      for joint replacement.

PMID- 17524005
TI  - Prioritization and resource allocation in health care: the views of older people
      receiving continuous public care and service.
AB  - OBJECTIVE: To describe the views of people, 65 years and over, receiving
      continuous public care and service, on prioritization and resource allocation in
      health care, in relation to gender, age, housing, health-related quality of life
      (QoL) and degree of activities of daily living (ADL) dependency. BACKGROUND: How
      older people receiving continuous public care and service view prioritization and
      resource allocation in health care is sparsely investigated, although this group
      most certainly has the experience and also often is the target in discussions
      concerning prioritization. It is necessary, for democracy and for the development
      of new models of service delivery, to find out how people receiving long-term
      care and service view these issues. DESIGN: 146 persons, 34 men (23%) and 112
      women (77%), aged 66-100 years were interviewed face to face, following a
      structured questionnaire. RESULTS: The respondents thought that the patients'
      well-being, way of living and family situation should affect prioritization, not
      age per se. Resourcing of several health-care services were considered to be
      below what is required by a majority of the respondents. The respondents wanted
      doctors to decide on prioritization at an individual level and wanted higher
      taxes to finance increasing health-care costs. Although the respondents wanted
      publicly financed health care, a relatively high number were willing to pay for
      treatment. CONCLUSIONS: Knowledge of how older people receiving care and
      services, view prioritization and resource allocation has not previously been
      available. It seems that their views are in line with the Swedish Parliamentary
      Priority Commission which suggested that no account should be taken of age when
      allocating resources within the health-care system. Respondents' age, gender,
      housing, health-related QoL and degree of dependency in ADL had limited influence
      on their views of resource allocation.

PMID- 17524006
TI  - Patient and public involvement: what next for the NHS?
AB  - INTRODUCTION: Patient and public involvement is the cornerstone of the 'patient
      led' National Health Service (NHS). Though the UK has had state sponsored
      arrangements for patient and public involvement since 1974, they have become
      fragmented and unstable. Patients' forums and the Commission for Patient and
      Public Involvement in Health replaced community health councils (CHCs) and their
      national association in England in 2003, but now will be replaced by local
      involvement networks (LINks) and the Commission will be abolished in 2007.
      LEARNING FROM HISTORY: This study provides an overview of research on the
      effectiveness of arrangements for patient and public involvement and reviews the
      debates about accountability, independence, ensuring consistency of performance,
      representation and how arrangements for the NHS fit within the wider agenda of
      citizenship and renewal of democracy. It explores key themes and areas for
      learning to inform the debate about how LINks might work effectively to improve
      the health of local people, in particular addressing issues of equity,
      representation and citizen engagement. CONCLUSIONS: The proposed LINks provide
      the opportunity to integrate patient and public involvement into wider
      initiatives for local democracy and citizen engagement. But debates and key
      issues about user and public involvement in the 1970s remain current and
      unresolved. If the new LINks are to succeed where forums and CHCs are considered
      to have failed, the strengths and weakness of both need to be understood and
      addressed.

PMID- 17524007
TI  - Improving sexual health services in the city: can the NHS learn from clients and
      the service industry.
AB  - OBJECTIVE: Genitourinary service providers are struggling to meet patient demand
      and have introduced changes in access structure to cope. In this study, we
      explored the perspectives of clients and providers upon the different models of
      access introduced and whether these maintained service quality using the SERQUAL
      model. METHODS: Primary data were collected in May 2005 at two genitourinary
      medicine clinics, two Accident and Emergency Departments and from members of a
      university 'gay' society all of which were located in London. Forty-four high
      risk clients and 11 health service providers underwent semi-structured face-to
      face interviews. RESULTS: Both the walk-in and appointment-based access systems
      were appreciated by clients. Clients said that the most important issue was that
      they were not turned away when they presented. Health-care providers had a
      variety of opinions about the two systems as they had different impacts on
      morale, training and service provision. CONCLUSIONS: Service quality can be
      maintained by using both walk-in and appointment-based systems. This is because
      our data, in line with Parasuraman's model of service quality, showed that
      'access' is but one determinant of quality. Having different modes of access
      facilitates patient choice, which is paramount in a modern health-care system.
      However, to provide a good service it is important to maintain a motivated staff,
      who can be affected by their working environment.

PMID- 17524008
TI  - Gender differences in colorectal cancer screening barriers and information needs.
AB  - CONTEXT: Several prior studies have found that women are less likely to be
      screened for colorectal cancer (CRC) than men. While the source of this screening
      differential is unknown, recent studies suggest gender differences in barriers to
      screening might explain the disparity. OBJECTIVE: This formative study was
      designed to explore CRC screening barriers, attitudes and preferences by gender.
      METHODOLOGY: Focus group interviews with groups stratified by gender and
      screening status. Participants included 27 females and 43 males between the ages
      of 50 and 75 years who receive primary care at the Minneapolis VA Medical Center.
      We conducted interpretive and grounded text analysis of semi-structured focus
      group interviews to assess how knowledge, experiences and sociocultural norms
      shape female and male preferences and barriers to current CRC screening
      guidelines. RESULTS: Female and male participants reported similar preferences
      for CRC screening mode, but there were notable differences in the barriers and
      facilitators to screening. Key findings suggest that women viewed the preparation
      for endoscopic procedures as a major barrier to screening while men did not;
      women and men expressed different fears and information preferences regarding
      endoscopic procedures; and women perceive CRC as a male disease thus feeling less
      vulnerable to CRC. Gender-specific barriers may explain women's lower rate of
      screening for CRC. CONCLUSION: Colorectal cancer screening promotion
      interventions, decision aids and clinical practice may benefit by being tailored
      by gender.

PMID- 17524009
TI  - Decision-making about mode of delivery after previous caesarean section:
      development and piloting of two computer-based decision aids.
AB  - OBJECTIVE: To develop and pilot two computer-based decision aids to assist women
      with decision-making about mode of delivery after a previous caesarean section
      (CS), which could then be evaluated in a randomized-controlled trial. BACKGROUND:
      Women with a previous CS are faced with a decision between repeat elective CS and
      vaginal birth after caesarean. Research has shown that women may benefit from
      access to comprehensive information about the risks and benefits of the delivery
      options. DESIGN: A qualitative pilot study of two novel decision aids, an
      information program and a decision analysis program, which were developed by a
      multidisciplinary research team. PARTICIPANTS AND SETTING: 15 women who had
      recently given birth and had previously had a CS and 11 pregnant women with a
      previous CS, recruited from two UK hospitals. Women were interviewed and observed
      using the decision aids. RESULTS: Participants found both decision aids useful
      and informative. Most liked the computer-based format. Participants found the
      utility assessment of the decision analysis program acceptable although some had
      difficulty completing the tasks required. Following the pilot study improvements
      were made to expand the program content, the decision analysis program was
      accompanied by a training session and a website version of the information
      program was developed to allow repeat access. CONCLUSIONS: This pilot study was
      an essential step in the design of the decision aids and in establishing their
      acceptability and feasibility. In general, participating women viewed the
      decision aids as a welcome addition to routine antenatal care. A randomized trial
      has been conducted to establish the effectiveness and cost-effectiveness of the
      decision aids.

PMID- 17524010
TI  - User involvement in the development of a research bid: barriers, enablers and
      impacts.
AB  - OBJECTIVE: To involve users in the development of a research bid to examine
      parents' experiences of having a pre-term baby, and to examine the barriers,
      enablers and impacts of user involvement. DESIGN: A mainly collaborative approach
      to user involvement was adopted, although different types of involvement were
      evident at different stages of the project. Users' experiences and perspectives
      provided the focus for the regular meetings which underpinned the writing of the
      research bid. The researcher acted as a facilitator in the development of the
      bid, with input from users and the wider advisory group. MAIN OUTCOMES: User
      involvement had an important impact on the development of the research aims,
      methods and on ethical aspects. Through careful collaboration a research bid was
      produced which was rooted in users' experiences, whilst also addressing key
      research questions. Key enablers for involvement included good working
      relationships, funding for the lead researchers time. Barriers included lack of
      financial support for users, the time-consuming nature of involvement and the
      language of research. CONCLUSIONS: If user involvement remains an international
      policy imperative with little if any support at the vital stage of bid
      development, policy-makers, service user organizations, researchers, health
      service providers and commissioners will need to recognize the limited nature of
      involvement that may result and the impact this would have on the evidence base.
      Researchers will need to recognize the resource implications of involvement at
      this point, and user groups will need to decide whether to participate when there
      is the greatest chance of influencing research but little or no funding.

PMID- 17524011
TI  - Men's interpretations of graphical information in a videotape decision aid.
AB  - OBJECTIVE: To examine men's interpretations of graphical information types viewed
      in a high-quality, previously tested videotape decision aid (DA). SETTING,
      PARTICIPANTS, DESIGN: A community-dwelling sample of men >50 years of age (N =
      188) balanced by education (college/non-college) and race (Black/White) were
      interviewed just following their viewing of a videotape DA. A descriptive study
      design was used to examine men's interpretations of a representative sample of
      the types of graphs that were shown in the benign prostatic hyperplasia videotape
      DA. MAIN VARIABLES STUDIED: Men provided their interpretation of graphs
      information presented in three formats that varied in complexity: pictograph,
      line and horizontal bar graph. Audiotape transcripts of men's responses were
      coded for meaning and content-related interpretation statements. RESULTS: Men
      provided both meaning and content-focused interpretations of the graphs. Accuracy
      of interpretation was lower than hypothesized on the basis of literature review
      (85.4% for pictograph, 65.7% for line graph, 47.8% for horizontal bar graph).
      Accuracy for pictograph and line graphs was associated with education level,
      chi2(1) = 3.94, P = 0.047, and chi2(1) = 7.55, P = 0.006, respectively. Accuracy
      was uncorrelated with men's reported liking of the graphs, chi2(1) = 2.00, P =
      0.441. CONCLUSION: While men generally liked the DA, accuracy of graphs
      interpretation was associated with format complexity and education level. Graphs
      are often recommended to improve comprehension of information in DAs. However,
      additional evaluation is needed in experimental and naturalistic observational
      settings to develop best practice standards for data representation.

PMID- 17524012
TI  - PartecipaSalute, an Italian project to involve lay people, patients' associations
      and scientific-medical representatives in the health debate.

PMID- 17524015
TI  - Literature names for pediatric medical conditions.
AB  - From the Grimm Brothers to Charles Dickens, from Gulliver's Travels to Alice's
      Adventures in Wonderland, great writers and stories have been a source for names
      of paediatric medical conditions, sometimes preceding the medical description by
      many years. This article describes the circumstances that led to the creation of
      some of these fascinating names, the physicians who coined them, and their link
      to the actual medical conditions. CONCLUSION: Literary names for medical
      conditions add warmth and humanity to the field of paediatrics.

PMID- 17524016
TI  - Motivated reasoning.

PMID- 17524017
TI  - Pulmonary function in non-atopic and atopic childhood asthma.

PMID- 17524018
TI  - Effect of early postnatal breastfeeding support: a cluster-randomized community
      based trial.
AB  - AIM: To assess the impact of a supportive intervention on the duration of
      breastfeeding. DESIGN AND SETTING: A community based cluster-randomized trial in
      Western Denmark. SUBJECTS: Fifty-two health visitors and 781 mothers in the
      intervention group, and 57 health visitors and 816 mothers in the comparison
      group. INTERVENTION: Health visitors in the intervention group received an 18-h
      course. The intervention addressed maternal psychosocial factors and consisted of
      1-3 home visits during the first 5 weeks post-partum. Health visitors in the
      comparison group offered their usual practice. MAIN OUTCOME MEASURE: Duration of
      exclusive breastfeeding during 6 months of follow-up. RESULTS: Mothers in the
      intervention group had a 14% lower cessation rate (HR = 0.86 CI: 0.75-0.99).
      Similar results were seen for primipara, and multipara with previously short
      breastfeeding experience. Mothers in the intervention group received their first
      home visit earlier, had more visits and practical breastfeeding training within
      the first 5 weeks. Babies in the intervention group were breastfed more
      frequently, fewer used pacifiers, and their mothers reported more confidence in
      not knowing the exact amount of milk their babies had received when being
      breastfed. CONCLUSION: Home visits in the first 5 weeks following birth may
      prolong the duration of exclusive breastfeeding. Postnatal support should focus
      on both psychosocial and practical aspects of breastfeeding. Mothers with no or
      little previous breastfeeding experience require special attention.

PMID- 17524019
TI  - The Nobel Prize for the introduction of ethology, or animal behaviour, as a new
      research field: possible implications for child development and behaviour.

PMID- 17524020
TI  - Lung disease in ataxia-telangiectasia.
AB  - Ataxia-telangiectasia (AT) is a multi-systemic disease caused by mutational
      inactivation of the ATM gene. We report a retrospective study of lung disease in
      15 patients. PATIENTS AND METHODS: A diagnosis of AT was made if the patient met
      the following criteria: neurological features and at least one the following:
      oculo-cutaneous telangiectasia, elevated serum alpha-feto-protein level. RESULTS:
      Recurrent sino-pulmonary infections were usually present in 11 of the cases and
      occurred during the first 2 years of life. Other lung injuries noted were
      bronchiectasis, obstruction and restriction of the airways, fibrosis,
      pneumothorax and haemoptysis. Eleven children had immunodeficiencies. DISCUSSION:
      Recurrent sino-pulmonary manifestations precede neurological complications, but
      the severity of neuro-degeneration and pulmonary disease were not correlated.
      Pulmonary status was a prognosis factor. Immunodeficiency was the main, but not
      the only, aetiology for lung disease in AT. CONCLUSION: There is little dispute
      over the role of ATM in lung and respiratory epithelium. To reduce the morbidity
      associated with AT, there needs to be greater awareness of respiratory
      complications. Early management and monitoring lung function is necessary to
      minimize lung damage.

PMID- 17524021
TI  - Trends in neonatology and pediatrics publications over the past 12 years.
AB  - OBJECTIVE: To test the hypothesis that the number of publications in Neonatology
      and Pediatrics increases over time, and to verify whether the categories of
      publications all follow the same pattern over time. DESIGN AND SETTING: We
      evaluated all Medline articles during 1994-2005. Search was limited to humans,
      English and to 'newborn' or 'all-child'. We used regression analysis to determine
      the effect of year-of-publication upon the number-of-publications of each type.
      RESULTS: Medline reported 36,141 publications in Neonatology and 169,823 in
      Pediatrics during the evaluation period. There was a significant linear increase
      in the number of publications in Neonatology and Pediatrics. There was a steady
      increase over time in Neonatology and in Pediatrics in meta-analyses, reviews and
      editorials. There was a steady decrease over time in letters in Neonatology, but
      no significant change in letters in Pediatrics. While there was no significant
      change in clinical trials (CTs), randomized control trials (RCTs) in Neonatology,
      there was a significant increase in CTs and RCTs in Pediatrics. CONCLUSIONS: The
      field of neonatology has not had a significant yearly increase of original
      studies, but has seen an increase of reviews, meta-analyses and editorials. This
      contrasts with Pediatrics, which shows a similar increase in reviews, meta
      analyses and editorials, but also an increase in the number of CTs and RCTs and
      guidelines.

PMID- 17524022
TI  - Growth factors gene expression in the developing lung.
AB  - AIM: This is the first systematic study using quantitative real-time PCR to
      analyze and compare the expression profiles for critical members of the epidermal
      growth factor (EGF), transforming growth factor beta (TGFbeta), and vascular
      endothelial growth factor (VEGF) families in developing rat lungs. METHODS: mRNA
      expression was quantified at embryonic (E) day 15, 17, 19, 21, and postnatal age
      1 day, 2 weeks, 12 weeks. RESULTS: EGF and EGFR increased during gestation and
      development, then decreased in adulthood, whereas TGFalpha was highest at birth
      and remained unchanged afterwards. All TGFbeta isoforms increased slightly during
      pregnancy, reached highest expression during development, and returned to
      neonatal levels in adulthood. TGFbetaRI and TGFbetaRII patterns were similar to
      TGFbeta2 and TGFbeta1 respectively, whereas TGFbetaRIII expression was lowest at
      the postnatal time points. VEGF(164) and VEGF(120) showed a steady increase up to
      2 weeks and declined at 12 weeks, whereas highest VEGF(188) expression occurred
      at 12 weeks. VEGF-A receptors expression paralleled the summation of all three
      isoforms, increasing steadily with age. CONCLUSION: Expression of growth factors
      in the developing lung is characterized by highly regulated distinctive patterns
      that may be critical to understand the early origin and progression of pulmonary
      diseases in childhood as well as in adulthood. Quantitative real-time PCR
      analysis revealed several differences compared to previously reported expression
      patterns defined with older methodologies.

PMID- 17524023
TI  - Helicobacter pylori infection among children with gastrointestinal symptoms: a
      high prevalence of infection among patients with reflux oesophagitis.
AB  - AIM: To investigate the link between H.pylori infection and dyspepsia in
      children, and association with reflux oesophagitis. PATIENTS AND METHODS:
      H.pylori status was detected by rapid urease test and/or culture in 130
      consecutive symptomatic children coming for upper gastrointestinal endoscopy: 40 
      aged 8-12 years (55% boys); 90 - aged 13-18 years (21% boys). Endoscopic
      findings were analyzed. H.pylori prevalence in the age group 8-12 years was
      compared to the prevalence among 55 asymptomatic children, aged 7-12 years (13C
      urea breath test). STATISTICAL ANALYSIS: chi(2) test, Fisher's test, and logistic
      regression analysis. RESULTS: The prevalence of H.pylori infection among patients
      with gastrointestinal symptoms was 54%. It was significantly higher among
      patients with reflux oesophagitis compared to patients with hyperaemic
      gastropathy: OR = 5.5; p = 0.03, 95% CI: 1.15-26.3. In logistic regression
      analysis, no significant difference between the prevalence of H.pylori infection
      between asymptomatic and symptomatic children could be demonstrated (OR = 1.8;
      95% CI: 0.62-5.14). CONCLUSIONS: The prevalence of H.pylori was significantly
      higher among patients with reflux oesophagitis compared to patients with
      hyperaemic gastropathy alone. Adjusting for age the prevalence of H.pylori
      infection was not higher among symptomatic children compared to asymptomatic
      children of the same age.

PMID- 17524024
TI  - Haplotypes of the surfactant protein genes A and D as susceptibility factors for
      the development of respiratory distress syndrome.
AB  - AIMS: Polymorphisms of genes are transmitted together in haplotypes, which can be
      used in the study of the development of complex diseases such as respiratory
      distress syndrome (RDS). The surfactant proteins (SPs) play important roles in
      lung function, and genetic variants of these proteins have been linked with lung
      diseases, including RDS. To determine whether haplotypes of SP-A and SP-D are
      transmitted disproportionately from parents to offspring with RDS, we
      hypothesized that previously unstudied genetic haplotypes of these SP genes are
      associated with the development of RDS. METHODS: DNA was collected from 132
      families of neonates with RDS. Genotyping was performed, and haplotype
      transmission from parent to offspring was determined by transmission
      disequilibrium test. RESULTS: The two-marker SP-D/SP-A haplotype DA160_A/SP-A2
      1A(1) is protective against the development of RDS (p = 0.035). Four three- and
      four-marker haplotypes containing one or both loci from the significant two
      marker haplotype are also protective against the development of RDS. CONCLUSIONS:
      These data identify protective haplotypes against RDS and support findings
      related to SP genetic differences in children who develop RDS. Study of
      haplotypes in complex diseases with both genetic and environmental risk factors
      may lead to better understanding of these types of diseases.

PMID- 17524025
TI  - Detection of cardiac pathology: time intervals and spectral analysis.
AB  - AIM: To develop an objective diagnostic method that facilitates detection of
      noncyanotic congenital heart diseases. METHODS: Heart sounds and murmurs were
      recorded from 60 healthy children and 173 children with noncyanotic congenital
      heart disease. Time intervals were measured and spectrum of the systolic murmurs
      analyzed. Stepwise logistic regression analysis was used to distinguish
      physiological from pathological signals. The receiver operating characteristic
      (ROC) curve was plotted to show the classification performance of the model and
      the area under the curve (AUC) was calculated. The probability cut-off points for
      calculation of sensitivities and specificities were estimated. RESULTS: The
      distinguishing variables were the interval from the end of the first heart sound
      (S(1)) and the beginning of the systolic murmur, respiratory variation of the
      splitting of the second heart sound, intensity of the systolic murmur, and
      standard deviation of the interval from the end of the S(1) to the maximum
      intensity of the murmur. The AUC was 0.95, indicating an excellent classification
      performance of the model. The sensitivity of 95% and specificity of 72% was
      achieved at a probability cut-off point of 0.45. Significant cardiac defects were
      correctly classified. CONCLUSION: Interval measurements and spectral analysis can
      be used to confirm significant noncyanotic congenital heart diseases. Further
      development of the method is necessary to detect also insignificant heart
      defects.

PMID- 17524026
TI  - Brain abnormalities in extremely low gestational age infants: a Swedish
      population based MRI study.
AB  - AIMS: Brain abnormalities are common in preterm infants and can be reliably
      detected by magnetic resonance (MR) imaging at term equivalent age. The aim of
      the present study was to acquire population based data on brain abnormalities in
      extremely low gestational age (ELGA) infants from the Stockholm region and to
      correlate the MR findings to perinatal data, in order to identify risk factors.
      METHODS: All infants with gestational age <27 weeks, born in the Stockholm region
      between January 2004 and August 2005, were scanned on a 1.5 T MR system at term
      equivalent age. Images were analysed using a previously established scoring
      system for grey and white matter abnormalities. RESULTS: No or only mild white
      matter abnormalities were observed in 82% and moderate to severe white matter
      abnormalities in 18% of infants. The Clinical Risk Index for Babies (CRIB II)
      score, use of inotropes, the presence of high-grade intraventricular haemorrhages
      and posthaemorrhagic ventricular dilatation were associated with white matter
      abnormalities. CONCLUSION: The incidence of moderate to severe white matter
      abnormalities in a population-based cohort of ELGA infants from the Stockholm
      region was 18%. To examine the clinical relevance of these promising results,
      neurodevelopmental follow up at 30 month corrected age, is ongoing.

PMID- 17524027
TI  - Quest for the diagnosis. Case 1: 12-year-old girl with high fever and increasing
      headache.

PMID- 17524028
TI  - Trends in the duration of school-day sleep among 10- to 15-year-old South
      Australians between 1985 and 2004.
AB  - AIM: To compare self-reported school-day sleep duration in 10- to 15-year-old
      South Australians between 1985 and 2004. METHODS: Data were collected from 10- to
      15-year-old participants in the 1985 Australian Schools Health and Fitness Survey
      (n = 390) and the 2004 South Australian Physical Activity Survey (n = 510).
      Identical self-report questionnaires were administered in both surveys, providing
      data on school-day bed-time, wake-time and sleep duration; as well as age, gender
      and socioeconomic status (SES). Analysis of co-variance (ANCOVA), controlling for
      age and SES, was used to compare all sleep variables between surveys. RESULTS:
      Declines in sleep duration were found for both girls (28 min) and boys (33 min)
      between surveys. The reduction was more pronounced in 'lower SES' boys (44 min)
      than 'higher SES' boys (23 min). Boys reported later bed-time than girls in the
      2004 survey, while no gender differences were apparent in the 1985 survey.
      CONCLUSION: Our findings suggest reductions in school-day sleep duration have
      occurred in Australian children and adolescents over the last 20 years, due
      largely to later bed-times. The physiological significance of these declines and
      mediating influences, such as SES, are yet to be explicated.

PMID- 17524029
TI  - Long-term (up to 18 years) effects on GH/IGF-1 hypersecretion and tumour size of
      primary somatostatin analogue (SSTa) therapy in patients with GH-secreting
      pituitary adenoma responsive to SSTa.
AB  - CONTEXT: The role of somatostatin analogues (SSTa) in the treatment of
      acromegaly. OBJECTIVE: To evaluate the antihormonal and antitumour efficacy of
      long-term (up to 18 years) primary treatment with SSTa in patients with GH
      secreting pituitary adenoma responsive to SSTa. DESIGN: An open, prospective,
      single-centre, clinical study. PATIENTS: Thirty-six acromegalic patients, aged 17
      75 years (postoral glucose tolerance test GH > 1 microg/l, increased IGF-1 for
      age and sex), were monitored in a single centre and treated with SSTa as first
      line therapy. The mean pretreatment GH level was 13.5 +/- 3.1 microg/l, and IGF-1
      (as a percentage of the value over the normal range) was 302 +/- 26%. The
      patients had macroadenoma (n = 25), microadenoma (n = 8) or empty sella turcica
      (n = 3). The mean duration of treatment was 8 years (range 3-18 years). Hormonal
      and morphological monitoring was undertaken after 6 months, and then the patients
      were followed annually. RESULTS: After 1 year, the mean GH and IGF-1 levels had
      reduced considerably (GH: 2.4 +/- 0.3 microg/l; IGF-1; 174 +/- 14%, P < 0.01),
      and they continued to decrease over 10 years, with a mean GH level of 1.6 +/- 0.1
      microg/l and IGF-1 of 123 +/- 18% (P = 0.02). GH < 2 microg/l, normal IGF-1, or
      both were observed in 25 (70%), 24 (67%) and 21 (58%) patients, respectively. The
      mean reduction in tumour volume was 43% (range 13-97%) and shrinkage > 20% was
      obtained in 21 patients (72%). SSTa treatment was well tolerated with few
      digestive or metabolic side-effects. CONCLUSION: Long-term (up to 18 years)
      treatment with SSTa used as first-line therapy is effective from both an
      antihormonal and antitumour perspective, and is well tolerated in acromegalic
      patients.

PMID- 17524030
TI  - The effect of single-dose orlistat on postprandial serum glucose, insulin and
      glucagon-like peptide-1 levels in nondiabetic obese patients.
AB  - OBJECTIVE: Glucagon-like peptide-1 is an insulin secretion-stimulating gut
      hormone that is produced in response to food intake. Orlistat (Xenical, F.
      Hoffman-La Roche, Basel, Switzerland), which decreases fat absorption and
      increases intestinal fat content, may therefore affect the secretion of glucagon
      like peptide-1. In this study we examined the immediate effects of orlistat on
      postprandial serum glucose, insulin and glucagon-like peptide-1 levels prior to a
      change in body weight. DESIGN: Randomized, clinical study. PATIENTS: Sixteen
      nondiabetic obese patients (body mass index 35.7 +/- 3.8 kg/m(2), range 32.5
      43.1) were enrolled in this study. The patients were randomly assigned to either
      the group treated with orlistat (120 mg, single dose) or the control group. There
      were eight patients in each of the two groups. Orlistat was given before a
      standard 600-kcal mixed meal containing 60% carbohydrates, 25% lipids and 15%
      protein. Blood samples were collected at baseline and at 30-min intervals for 180
      min after the test meal. Graphical tendencies, peak value, time to reach the peak
      value, and area under the curve in the two groups were compared. MEASUREMENTS:
      Blood samples were obtained for the measurement of GLP-1, glucose, insulin, high
      density lipoprotein, total cholesterol and triglycerides. RESULTS: We found no
      difference in sex distribution, mean age, anthropometric measurements, or
      baseline glucose, insulin and glucagon-like peptide-1 levels between the orlistat
      and placebo groups. The peak insulin and glucagon-like peptide-1 levels were
      determined at 60 min in the control group. Hourly changes in serum glucose and
      insulin levels were similar between the groups, although the peak insulin and
      glucagon-like peptide-1 levels were reached at 120 min in the orlistat group.
      There were no statistically significant differences between the groups.
      CONCLUSIONS: A single dose of 120-mg orlistat caused no change in postprandial
      serum glucose, insulin or glucagon-like peptide-1 levels in nondiabetic obese
      patients. Although glucagon-like peptide-1 increases were delayed in the orlistat
      group, these changes were nonsignificant.

PMID- 17524031
TI  - Altered cardiovascular vagal responses in nonelderly female patients with
      subclinical hyperthyroidism and no apparent cardiovascular disease.
AB  - OBJECTIVE: Subclinical hyperthyroidism (SH) has been associated with exercise
      intolerance, changes in cardiac morphology, atrial arrhythmias and sympathovagal
      imbalance. The aim of this study was to evaluate the vagal reserve and modulation
      by a sympathetic stimulus in nonelderly patients with SH without cardiovascular
      problems. DESIGN: We carried out a cross-sectional study, comparing data of the
      heart rate variability (HRV) of SH patients and healthy controls at rest and
      after vagal and sympathetic stimulation. PATIENTS: We studied 16 female patients
      with at least 6 months of SH and 16 healthy female controls with the same median
      age (40 vs. 34.5 years). MEASUREMENTS: We used the tilt test, with
      electrocardiographic record at rest, during the respiratory sinus arrhythmia
      (RSA) manoeuvre and after tilting, in order to analyse HRV in the frequency
      domain (%high frequency (HF) and low/high frequency ratio (LF/HF) using
      Biopotentials Captation System software. RESULTS: The median TSH level was 0.03
      mU/l in patients and 1.37 mUI/l in controls. The median free T4 was 1.37 ng/dl in
      patients and 1.20 ng/dl in controls. Patients demonstrated a significantly
      smaller difference between %HF during the RSA and %HF at rest than controls
      (median -7.5 vs. 36.6, P < 0.001). There was a lower difference between LF/HF
      ratio after tilting and LF/HF ratio at rest in patients than in controls (1.5 vs.
      5.3, P = 0.005). CONCLUSION: Subclinical hyperthyroidism affects cardiovascular
      autonomic balance in otherwise apparently healthy nonelderly females by blunting
      vagal responses.

PMID- 17524032
TI  - W546X mutation of the thyrotropin receptor causes subclinical hypothyroidism in
      various clinical settings.

PMID- 17524033
TI  - Circulating sex hormones and gene expression of subcutaneous adipose tissue
      oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for
      fat distribution.
AB  - OBJECTIVE: Circulating oestradiol and testosterone, which have been shown to
      increase in human immunodeficiency virus (HIV)-infected patients following highly
      active antiretroviral therapy (HAART), may influence fat distribution and insulin
      sensitivity. Oestradiol increases subcutaneous adipose tissue in humans possibly
      through binding to oestrogen-receptor-alpha, which in turn activates anti
      lipolytic alpha2A-adrenergic-receptor. DESIGN AND METHODS: To address these
      issues circulating pituitary-gonadal-axis hormones and gene expression of
      receptors in subcutaneous adipose tissue were determined in 31 nondiabetic HIV
      infected male patients receiving HAART (16 with lipodystrophy), in whom measures
      of fat distribution (CT and DEXA-scans) and insulin sensitivity
      (hyperinsulinaemic euglycaemic clamp) were available. RESULTS: Total and free
      oestradiol and testosterone were decreased in lipodystrophic patients compared to
      nonlipodystrophic patients, whereas luteinizing hormone, follicle-stimulating
      hormone and prolactin were similar and normal in both study groups. Ratio of
      subcutaneous to total abdominal fat mass, limb fat, and insulin sensitivity,
      which were all decreased in lipodystrophic patients, correlated positively with
      both plasma oestradiol and testosterone (n = 31). Glycerol concentration during
      clamp (a marker of lipolysis) correlated inversely with expression of alpha2A
      adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb
      fat, respectively. Expression of alpha2A-adrenergic-receptor correlated
      positively with expression of oestrogen-receptor-alpha. CONCLUSIONS: The results
      fit the hypothesis that sex hormones play a role in altered fat distribution and
      insulin sensitivity of male patients with HIV-lipodystrophy. The effect of
      oestradiol on the subcutaneous fat depot and lipolysis may be mediated in part
      through binding to the oestrogen-receptor-alpha, in turn activating anti
      lipolytic alpha2A-adrenergic-receptor.

PMID- 17524034
TI  - Familial partial lipodystrophy due to the LMNA R482W mutation with multinodular
      goitre, extrapyramidal syndrome and primary hyperaldosteronism.
AB  - Objective To describe new data about the wide phenotypic variability of diseases
      due to mutations in the lamin A/C gene (LMNA). Design We report a complex
      phenotype in a patient with familial partial lipodystrophy of the Dunnigan type
      (FPLD) and study the frequency of her unusual clinical signs in 19 other LMNA
      mutated lipodystrophic patients from 8 different families and 14 non-mutated
      family members. Case Report The patient was diagnosed with FPLD due to the R482W
      LMNA mutation after familial screening. Surprisingly, she had no biological signs
      of insulin resistance. The presence of hypertension with hypokalaemia led to the
      diagnosis of primary hyperaldosteronism. Thyroid investigations showed a
      euthyroid multinodular goiter. In addition, the patient exhibited a juvenile
      akineto-hypertonic syndrome. Results Goiter was identified with a similar
      frequency (55%) in LMNA-mutated lipodystrophic patients (11 out of 20,
      originating from 5 families among 8) compared to non-mutated family controls
      (35%; 5 patients out of 14, all originating from the same family). No case of
      primary hyperaldosteronism or extrapyramidal syndrome was identified in other
      studied subjects, either LMNA-mutated or not. Conclusions This R482W-LMNA mutated
      patient showed an association of features (primary hyperaldosteronism, euthyroid
      goiter and extra-pyramidal syndrome, raising the question of a link with her
      laminopathy. Prevalence of goiter tended to be higher in LMNA-mutated than in non
      mutated subjects. Hyperaldosteronism seems coincidental. Although extrapyramidal
      syndrome has never been reported in lipodystrophic patients, it may nevertheless
      be linked to the LMNA mutation since multiple neurological features have been
      associated with alterations in lamins A/C.

PMID- 17524035
TI  - Prevalence and predictive factors of post-traumatic hypopituitarism.
AB  - OBJECTIVE: To estimate the prevalence and predictive factors of hypopituitarism
      following traumatic brain injury (TBI). DESIGN: A cross-sectional cohort study.
      PATIENTS: One hundred and four hospitalized TBI patients (26F/78M), median age 41
      (range 18-64) years, body mass index (BMI) 25 (17-39) kg/m(2); severity: mild
      [Glasgow Coma Scale (GCS) score 13-15) n = 44, moderate (GCS 9-12) n = 20, severe
      (GCS < 9) n = 40]. MEASUREMENTS: Patients were evaluated 13 (10-27) months post
      injury, with measurement of baseline (0800-1000 h) and post-stimulatory hormonal
      levels during an insulin tolerance test (ITT) (86%) or, if contraindicated, an
      arginine(arg)-GHRH test + Synacthen test (14%). Insufficiencies were confirmed by
      retesting. RESULTS: Hypopituitarism was found in 16 (15%) patients, affecting one
      axis in 10, two axes in four and more than two axes in two patients. The GH axis
      was most frequently affected (15%), followed by secondary hypoadrenalism (5%),
      hypogonadism (2%), hypothyroidism (2%) and diabetes insipidus (2%). The risk of
      pituitary insufficiency was increased in patients with severe TBI as opposed to
      mild TBI [odds ratio (OR) 10.1, 95% confidence interval (CI) 2.1-48.4, P =
      0.004], and in those patients with increased intracerebral pressure [OR 6.5, 95%
      CI 1.0-42.2, P = 0.03]. Patients with only one affected axis were all GH
      deficient; 60% (n = 6) of these were overweight or obese. CONCLUSION: The
      prevalence of hypopituitarism was estimated at 16%. Although high, this value was
      lower than previously reported, and may still be overestimated because of well
      known confounding factors, such as obesity. Indicators of increased TBI severity
      were predictive of hypopituitarism, with a high negative predictive value.
      Neuroendocrine evaluation should therefore be considered in patients with severe
      TBI, and in particular in those with increased intracerebral pressure (ICP).

PMID- 17524037
TI  - Plasma phospholipid transfer protein activity, a determinant of HDL kinetics in
      vivo.

PMID- 17524038
TI  - How do we improve outcomes for gastric cancer?
AB  - Although the incidence of gastric cancer is decreasing globally, it remains the
      second leading cause of cancer death, accounting for 600,000 deaths annually
      worldwide. It is particularly common in Asia and especially in China, Japan and
      Korea. In Singapore, it is the fourth commonest cancer in men, who have a 1:50
      lifetime risk of developing gastric cancer. Gastric cancer traditionally carries
      a poor prognosis because of late presentation at an advanced stage of disease. If
      diagnosed at an early stage, it is a curable disease. Four strategies will
      systematically help to improve outcomes for gastric cancer: (i) early detection
      by screening of high-risk groups; (ii) clarification of the hypothesis that
      Helicobacter pylori eradication in endemic areas with a high incidence of gastric
      cancer is an effective primary prevention strategy; (iii) improvement of
      treatment by well-designed clinical trials, coupled with molecular
      characterization of tumors; and (iv) improving our biological understanding of
      gastric carcinogenesis.

PMID- 17524039
TI  - Safety, tolerability and satisfaction with tegaserod therapy in Asia-Pacific
      patients with irritable bowel syndrome with constipation.
AB  - BACKGROUND AND AIM: The 5-HT(4) receptor agonist tegaserod (6 mg b.i.d.) provides
      significantly better overall multiple symptom relief compared with placebo in
      patients with irritable bowel syndrome with constipation (IBS-C). The clinical
      benefit and safety of tegaserod in IBS-C patients has been demonstrated worldwide
      in several studies. The aim of this study was to obtain further safety and
      tolerability data in patients with IBS in the Asia-Pacific region, and to assess
      patients' satisfaction and compliance with treatment and willingness to re-use
      tegaserod in a post-marketing setting. METHODS: A multicenter, single-arm, open
      label trial was conducted at 869 outpatient centers in 10 countries. Men and
      women with IBS, whose predominant bowel symptom was not diarrhea (non-D-IBS),
      received tegaserod for 4-12 weeks. Safety and tolerability were assessed by
      recording adverse events (AE). Patients were questioned about compliance,
      satisfaction with treatment and willingness to use tegaserod in future. RESULTS:
      Data were available from 14 537 patients (18% men, 82% women). Four percent of
      patients reported at least one AE. The most common AE were diarrhea (2%) and
      abdominal pain (1%), and most treatment-related AE occurred in the first week of
      treatment. Serious AE (SAE) were observed in eight patients, and no deaths were
      reported. Most patients (79%) reported to be satisfied or very satisfied with
      treatment, and 76% stated they would use tegaserod in the future. Compliance was
      97%. CONCLUSIONS: Tegaserod has a favorable safety and tolerability profile for
      treating non-D-IBS and IBS-C in men and women in the Asia-Pacific region.
      Satisfaction with tegaserod treatment can be expected in the majority of
      patients.

PMID- 17524040
TI  - Androgen profiles among Egyptian adults considering liver status.
AB  - BACKGROUND AND AIM: Hepatitis C virus (HCV) and environmental hepatotoxins may
      have an indirect influence on health by altering the synthesis and function of
      hormones, particularly reproductive hormones. We aimed to evaluate liver diseases
      and sex steroid hormones in Egypt, which has the highest prevalence of HCV
      worldwide. METHODS: We measured markers of hepatitis B virus (HBV), HCV and
      schistosomiasis infection as well as liver function in 159 apparently healthy
      subjects. We measured total testosterone (T), sex-hormone binding globulin (SHBG)
      and albumin, and calculated the free androgen index. RESULTS: Anti-HCV antibodies
      were detected in 51% of men and 42% of women. Based on HCV reverse transcription
      PCR (RT-PCR) of 44 men and 33 women, 11% of men and 21% of women showed HCV
      viremia. There was schistosomiasis in 25% of men and 9% of women, and mixed HCV
      viremia and schistosomiasis in 57% of men and 52% of women. Compared with men
      with schistosomiasis only (mean 593.3 +/- 73.4 ng/dL), T was higher in men with
      mixed HCV viremia and schistosomiasis (mean 854.5 +/- 47.9 ng/dL; P = 0.006) and
      men with mixed chronic HCV and schistosomiasis (mean 812.1 +/- 43.3 ng/dL; P =
      0.001). Men with mixed chronic HCV and schistosomiasis had also significantly
      higher SHBG (mean 57.7 +/- 3.9 ng/dL) than males with schistosomiasis only (mean
      34.8 +/- SE 4.5 ng/dL; P = 0.0003). CONCLUSION: Future investigations should
      consider that a high prevalence of asymptomatic liver disease may alter
      associations between hormone concentrations and chronic disease etiology.

PMID- 17524041
TI  - Retraction. Clinical presentation and diagnosis of sigmoid volvulus: outcomes of
      40-year and 859-patient experience.

PMID- 17524042
TI  - Heparanase expression in gallbladder carcinoma and its correlation to prognosis.
AB  - BACKGROUND AND AIM: Heparanase is an endo-beta-glucuronidase that cleaves heparan
      sulfate and has been implicated in tumor angiogenesis and metastasis. The present
      study was to analyze the expression of and explore the prognostic value of
      heparanase and two important transcriptional factors, namely hypoxia-inducible
      factor-1alpha (HIF-1alpha) and nuclear transcriptional factor kappa B p65 (NF
      kappaB p65) in gallbladder cancer. METHODS: Heparanase, HIF-1alpha and NF-kappaB
      p65 protein levels in 38 patients with gallbladder carcinoma were detected by
      immunohistochemistry and analyzed for clinicopathological significance. RESULTS:
      The heparanase, HIF-1alpha and NF-kappaB p65 proteins were found in 24 (63.2%),
      13 (34.2%) and 22 (57.9%) specimens, respectively. High heparanase expression was
      closely related to advanced TNM stage (P = 0.007), depth of tumor invasion (P =
      0.016), lymph node metastasis (P = 0.040) and decreased postoperative survival at
      3 years (50.0% vs 20.8%, P = 0.001). Both HIF-1alpha and NF-kappaB p65 proteins
      were correlated with tumor size (P = 0.039 and P = 0.027, respectively) and
      patients positive for HIF-1alpha expression had a decreased survival rate
      compared with those negative for HIF-1alpha expression (40.0% vs 15.4%, P =
      0.035). In addition, heparanase-positive cases had high expression of NF-kappaB
      p65 compared with the heparanase-negative cases (P = 0.047). CONCLUSION:
      Heparanase and HIF-1alpha are frequently expressed in gallbladder carcinoma and
      are associated with decreased survival. High expression of heparanase, combined
      with NF-kappaB p65, may contribute to the highly invasive and metastatic behavior
      of gallbladder carcinoma.

PMID- 17524043
TI  - Relationships among the nurse work environment, self-nurturance and life
      satisfaction.
AB  - AIM: This paper is a report of a study to (1) ascertain the relationship among
      self-nurturance, perceived Magnet features and life satisfaction and (2) evaluate
      the predictive effects of self-nurturance and Magnet features on life
      satisfaction. BACKGROUND: Promoting health is a global priority for nurses and
      for the public who depend upon them to provide quality care. Health gains can be
      realized by modifying the work environment and by modifying lifestyle choices
      (self-nurturance). A study of nurses that examined perceptions of workplace
      features that enable nurses' professional practice (Magnet features), self
      nurturance and healthy outcomes (life satisfaction) was not found in the
      literature. METHODS: Survey data collected in May 2003 from a convenience sample
      of 310 Registered Nurses were used for this descriptive, correlational study.
      FINDINGS: Self-nurturing nurses were more satisfied with life and perceived that
      more Magnet features were present in the workplace. Nurses with a master's degree
      were more self-nurturing than nurses without a baccalaureate degree. The
      synergistic effect of both self-nurturance and workplace factors predicted 29% of
      variance in nurses' life satisfaction. CONCLUSION: Higher levels of perceived
      Magnet features and frequent self-nurturance choices are important health
      influences on nurses' life satisfaction. Greater life satisfaction is known to
      reduce job dissatisfaction while improving retention. Approaches that incorporate
      both self-nurturance and workplace Magnet features are suggested to improve the
      health and retention of experienced nurses.

PMID- 17524044
TI  - Home percutaneous endoscopic gastrostomy feeding: perceptions of patients,
      carers, nurses and dietitians.
AB  - AIM: This paper is a report of a study to compare the perceptions of adult
      patients, family carers, nurses and dietitians regarding home percutaneous
      endoscopic gastrostomy feeding. BACKGROUND: Healthcare professionals have a major
      role in patient selection for gastrostomy placement and the provision of
      aftercare but it is not clear if patients, their carers and healthcare
      professionals have similar perceptions of the initiation and delivery of feeding
      and of the care in general. METHOD: A cross-sectional mixed-method study using
      purposive sampling, semi-structured interviews and questionnaires was performed.
      Interviews were undertaken during 2005 with adult patients and carers of adults
      receiving home feeding. A questionnaire containing comparable questions was
      distributed to the lead district nurse and dietitian providing the individual
      patient's care. Binomial regression was used to analyse any differences in
      perceptions across the groups of respondents. RESULTS: Nurses and dietitians had
      similar perceptions of gastrostomy feeding in adults. Family carers' perceptions
      matched those of professionals more closely than did those of patients. The
      greatest difference in perceptions was between patients and their family carers.
      Respondents' views about success of feeding and the appropriateness of the
      feeding regimen were similar, but greater differences existed regarding quality
      of life, withdrawal of feeding and choice in decision-making about tube
      placement. CONCLUSION: There is a need for increased patient and carer
      involvement in decision-making and for sufficient, appropriate information to
      facilitate informed decision-making. Practitioners who involve carers in decision
      making, where patients lack capacity, need to be aware that carers may not
      represent the views of patients.

PMID- 17524045
TI  - Pretreatment preparation and management of interferon-based therapy for hepatitis
      C virus infection.
AB  - AIM: This paper is a report of a study to explore how healthcare professionals
      prepare patients for hepatitis C treatment and the management strategy used
      during this treatment. BACKGROUND: A high proportion of patients receiving
      hepatitis C treatment has dose reductions or discontinues treatment because of
      adverse events arising from the therapeutic drugs. METHOD: An exploratory study
      was carried out in Australia in 2004 and 2005 using semi-structured interviews
      with a sample of six healthcare professionals with experience in managing
      hepatitis C treatment regimens. FINDINGS: Participants reported that pretreatment
      preparation focused on information provision regarding the adverse events and the
      medical strategies that could ameliorate their impact. Patients' vulnerabilities
      and supports were assessed prior to treatment and healthcare professionals sought
      to address patients' problems as they arose during treatment. Participants
      discussed patients' resilient coping style and the beneficial impact this had on
      treatment management. CONCLUSION: Among our sample, a deficits-based approach was
      taken to hepatitis C treatment management. While some attempts were made to
      assess patients' strengths, these were limited to identifying those in family,
      work and social networks who could lend support to patients when problems
      occurred. Exploring patients' past experiences of adversity and making a detailed
      evaluation of a range of patients' strengths might assist clinicians in managing
      hepatitis C treatment regimens.

PMID- 17524046
TI  - Equivalence of Chinese version of the Cohen-Mansfield Agitation Inventory.
AB  - AIM: This paper is a report of a study undertaken to translate the Cohen
      Mansfield Agitation Inventory from the original English into a Chinese language
      version and to establish the content, semantic and technical equivalence of the
      Chinese version. BACKGROUND: Ensuring the equivalence of a translated Chinese
      version of the Cohen-Mansfield Agitation Inventory for patients with dementia is
      an essential requirement for identifying culturally specific expressions of
      agitated behaviours. METHODS: In Phase I, five experts scrutinized the Inventory
      items to determine whether the behaviour described was relevant to the agitated
      behaviours present in the Taiwanese culture. In Phase II, experts did the initial
      translation into Chinese and then back-translated it into English. Four bilingual
      observers rated 31 residents with dementia to determine semantic equivalence
      across versions. In Phase III, the agitated behaviours of 32 residents were
      assessed by four observers using staff ratings and direct observation to
      determine the technical equivalence of the Chinese version. The study was carried
      out in Taiwan from August 2004 to April 2005. FINDINGS: In Phase I, the rating of
      behaviours described on the Cohen-Mansfield Agitation Inventory was relevant to
      the agitated behaviours based on Taiwanese culture with a content validity index
      (CVI) value of 0.993. In Phase II, intra-class coefficients for all items on the
      Chinese version and split-halves of Chinese and English versions ranged from 0.69
      to 0.74. In Phase III, six possible results for estimation of reliability across
      methods and raters for the Chinese version ranged from 0.63 to 0.86. CONCLUSION:
      The Chinese Cohen-Mansfield Agitation Inventory had modest psychometric
      properties. Further studies are needed to assess criterion and conceptual
      equivalence.

PMID- 17524047
TI  - Intraprofessional relations in nursing.
AB  - AIM: This paper is a report of a study to explore the way in which Registered
      Nurses relate to and interact with each other in the workplace, and to identify
      factors that influence nurses' interactions with each other. BACKGROUND:
      Intraprofessional relations are an important topic both for nurses and nursing as
      we face the ongoing challenges of nurse shortages. Poor colleague relationships,
      together with workplace conflict, cause job dissatisfaction. As a consequence,
      some nurses leave the profession while others continue working but remain
      chronically unhappy. METHOD: An explanatory multiple case study design was
      adopted. Data were collected from multiple sources on three different wards
      within one hospital in Australia between July 2005 and January 2006. FINDINGS:
      The workplace can be a difficult place for both very experienced and less
      experienced nurses, regardless of the clinical environment. Nurses navigate their
      way in the workplace through a series of complex negotiations with each other and
      develop skills to assess the potential success of an interaction before
      approaching another nurse. Some also develop a resilience to conflict in their
      workplace, accepting it as part of working life. CONCLUSION: Creation of a more
      positive work environment requires increased understanding of the way nurses
      relate to each other and appreciation of the factors in the environment that
      contribute to conflict and a negative atmosphere. This appreciation is a
      necessary prerequisite to developing a more satisfying and productive workplace
      enhancing the recruitment of new nurses and the retention of experienced nurses.

PMID- 17524048
TI  - Impact of nurse prescribing: a qualitative study.
AB  - AIM: This paper is a report of an investigation of the impact of prescribing on a
      group of recently qualified nurse prescribers in the United Kingdom. BACKGROUND:
      The creation of advanced nursing roles, and specific skills such as nurse
      prescribing, has resulted in nurses taking on roles that have traditionally been
      associated with doctors. The non-doctor prescribing initiative is continually
      developing and many nurses are now able to prescribe independently from almost
      the same range of medicines as doctors. Despite the advantages that appear to
      stem from nurses prescribing, some nurse researchers have been cautious about the
      impact that prescribing may have on the nursing profession. METHOD: Interviews
      were conducted during 2005 and 2006 with 45 nurse prescribers. All nurses had
      successfully qualified and registered as prescribers. Interviews were analysed
      thematically in line with the principles of grounded theory. FINDINGS:
      Prescribing allows nurses to overcome difficulties in the healthcare system that
      previously delayed patients' access to medicines. Prescribing is viewed as more
      than an 'add on' to current roles, it complements many aspects of nursing and
      integrates previously diffuse aspects of the nursing role. This enables nurses to
      adopt a more holistic approach to patient care and prescribing. Prescribing has
      the potential to increase job satisfaction and autonomous working, with the
      result that nurses are more likely to involve patients in decision-making about
      their care. CONCLUSIONS: Prescribing enhances nurses' knowledge about medication
      and increases their confidence to engage in prescribing decisions across the
      healthcare team. Nurse prescribing has the potential to improve service-user
      care, enhance collaboration and widen discussions about medicines. However, team
      members need to be prepared for the impact nurse prescribing could have on the
      dynamics of the multidisciplinary team. Preparatory information about nurse
      prescribing should be provided to all team members by trainee nurse prescribers.
      Information could include details about the proposed scope of future prescribing
      roles, allowing team members to consider how their roles could develop.

PMID- 17524049
TI  - Production of glucocerebrosidase with terminal mannose glycans for enzyme
      replacement therapy of Gaucher's disease using a plant cell system.
AB  - Gaucher's disease, a lysosomal storage disorder caused by mutations in the gene
      encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement
      therapy using recombinant GCD (Cerezyme) expressed in Chinese hamster ovary (CHO)
      cells. As complex glycans in mammalian cells do not terminate in mannose
      residues, which are essential for the biological uptake of GCD via macrophage
      mannose receptors in human patients with Gaucher's disease, an in vitro glycan
      modification is required in order to expose the mannose residues on the glycans
      of Cerezyme. In this report, the production of a recombinant human GCD in a
      carrot cell suspension culture is described. The recombinant plant-derived GCD
      (prGCD) is targeted to the storage vacuoles, using a plant-specific C-terminal
      sorting signal. Notably, the recombinant human GCD expressed in the carrot cells
      naturally contains terminal mannose residues on its complex glycans, apparently
      as a result of the activity of a special vacuolar enzyme that modifies complex
      glycans. Hence, the plant-produced recombinant human GCD does not require
      exposure of mannose residues in vitro, which is a requirement for the production
      of Cerezyme. prGCD also displays a level of biological activity similar to that
      of Cerezyme produced in CHO cells, as well as a highly homologous high-resolution
      three-dimensional structure, determined by X-ray crystallography. A single-dose
      toxicity study with prGCD in mice demonstrated the absence of treatment-related
      adverse reactions or clinical findings, indicating the potential safety of prGCD.
      prGCD is currently undergoing clinical studies, and may offer a new and
      alternative therapeutic option for Gaucher's disease.

PMID- 17524050
TI  - Rodents as taphonomic agents: bone gnawing by brown rats and gray squirrels.
AB  - Passive infrared technology was used to film diurnal and nocturnal scavenging
      behavior of brown rats and gray squirrels at the University of Tennessee's
      Anthropological Research Facility. This direct documentation demonstrated that
      brown rats modified fat-laden cancellous bone while gray squirrels generally
      gnawed the thicker bone cortices only after fats had leached away. A case study
      placed in a shaded portion of the Facility indicated the postmortem interval for
      initial gnawing by gray squirrels was slightly over 30 months. An examination of
      53 human skeletons in the William M. Bass Forensic Skeletal Collection revealed
      that 10 cases had gnaw marks consistent with those made by gray squirrels. One of
      the 10 cases had been gnawed within 16 months of time-since-death, while the
      remaining nine had postmortem intervals >30 months. Additional observed
      modifications made to nonhuman bone by gray squirrels indicate that squirrel gnaw
      marks on bone can serve as a minimal estimate of time-since-death in a temperate
      environment similar to that of East Tennessee.

PMID- 17524051
TI  - The use of geographic information systems as a forensic tool to investigate
      sources of marine mammal entanglement in fisheries.
AB  - Commercial fisheries represent a significant anthropogenic threat to marine
      mammal survival. Causes of marine mammal mortality are commonly determined by
      detailed necropsies of stranded carcasses. Gross evidence of entanglement in a
      fishery might include gear attached to the body, internal indications of
      asphyxiation and trauma, or gear markings on the epidermis. As gear is often
      fishery-specific, wound patterns on the epidermis that are created by
      entanglements in fishing gear may serve to identify possible sources of
      mortality. For this study, tools within the Environmental Systems Research
      Institute, Inc. (ESRI) ArcMap GIS software were used to create maps that outline
      impressions that fishing gear can leave on the epidermis of entangled marine
      mammals. These maps can subsequently be used to identify possible sources of
      fishery entanglement for the many marine mammals that wash ashore without gear
      attached to their carcass. Entanglement wound patterns can be visually compared
      with fishing gear characteristics; however, differences in scale and image
      quality can introduce subjectivity that might hinder source identification. The
      technique described herein provides an objective way to outline the unique
      characteristics of fishing gear and their associated wounds on entangled marine
      mammals. Additionally, spatial relationships are preserved as the maps are
      adjusted to varying scales. Whereas the initial protocol required time-consuming
      digitization of the outline and visual determination of the pattern interface,
      this new, semiautomated technique saves analyst effort and minimizes error.

PMID- 17524052
TI  - Typeability of AmpFlSTR SGM Plus loci in brain and thyroid gland tissue samples
      incubated in different environments.
AB  - Autolysis and putrefaction are crucial factors responsible for degradation of
      cells, tissues, and organs. Postmortem changes may assume different course
      depending on extrinsic and intrinsic conditions. The aim of the study was
      assessment of environmental effect on typeability of AmpFlSTR SGM Plus loci:
      D3S1358, VWA, D16S539, D2S1338, D81179, D21S11, D18S51, D19S433, TH01, FGA, and
      gender marker amelogenin. Brain and thyroid gland tissue specimens collected
      during autopsies of five persons aged 20-30 years were incubated at 21 degrees C
      and 4 degrees C in different environmental conditions. DNA was extracted by
      organic method from tissue samples collected in 7-day intervals and subsequently
      typed using AmpFlSTR SGM Plus kit and ABI 310. A fast decrease in typeability
      rate was seen in specimens incubated in peat soil and in sand. Brain tissue
      samples were typeable in all AmpFlSTR SGM Plus loci within 126 days of incubation
      at 4 degrees C. Faster DNA degradation was recorded in thyroid gland specimens.
      In samples with negative genotyping results, no DNA was found by fluorometric
      quantitiation.

PMID- 17524053
TI  - Quality assurance testing of an explosives trace analysis laboratory--further
      improvements.
AB  - The Forensic Explosives Laboratory (FEL) operates within the Defence Science and
      Technology Laboratory (DSTL) which is part of the UK Government Ministry of
      Defence (MOD). The FEL provides support and advice to the Home Office and UK
      police forces on matters relating to the criminal misuse of explosives. During
      1989 the FEL established a weekly quality assurance testing regime in its
      explosives trace analysis laboratory. The purpose of the regime is to prevent the
      accumulation of explosives traces within the laboratory at levels that could, if
      other precautions failed, result in the contamination of samples and controls.
      Designated areas within the laboratory are swabbed using cotton wool swabs
      moistened with ethanol water mixture, in equal amounts. The swabs are then
      extracted, cleaned up and analyzed using Gas Chromatographs with Thermal Energy
      Analyzer detectors. This paper follows on from a previous published paper
      describing the regime and summarizing subsequent results from approximately 6
      years of tests. Lessons learned and improvements made over the period are also
      discussed. Monitoring samples taken from surfaces within the trace laboratories
      and trace vehicle examination bay have, with few exceptions, revealed only low
      levels of contamination, predominantly of RDX. Analysis of the control swabs,
      processed alongside the monitoring swabs, has demonstrated that in this
      environment the risk of forensic sample contamination, assuming all the relevant
      anti-contamination procedures have been followed, is so small that it is
      considered to be negligible. The monitoring regime has also been valuable in
      assessing the process of continuous improvement, allowing sources of
      contamination transfer into the trace areas to be identified and eliminated.

PMID- 17524054
TI  - Does hyperthyroidism increase risk of death due to the ingestion of ecstasy?
AB  - Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive amphetamine
      derivative widely used for recreational purposes. Deaths caused by acute drug
      intoxication with MDMA are rare but can often involve a severe hyperthermic
      episode. The factors underlying the increased risk of some ecstasy users to a
      fatal drug reaction are not known. We present a case report of a 24-year-old
      woman who developed fatal hyperthermia with multi-organ complications following
      MDMA use and was found at autopsy to have diffuse thyroid hyperplasia (Graves'
      disease). An antemortem blood MDMA concentration of 0.68 mg/L was measured in a
      sample obtained on admission to hospital. Although a cause and effect cannot be
      established, as the thyroid hormone is a major regulator of thermogenesis, we
      suggest that hyperthyroidism predisposed the subject to ecstasy-induced
      hyperthermia and that a pre-existing defect affecting temperature status could be
      one factor in explaining some ecstasy intoxication deaths.

PMID- 17524055
TI  - A case of multiple assignments (paternity/maternity) in an equine-out breeding
      system.
AB  - Recently, the use of DNA markers has provided a more accurate method of
      identifying individuals and verifying parentage. In this report, we describe foal
      assignment in a farm bred jumping horses (Silla argentino). Ten mares were freely
      served by two stallions, resulting in nine foals. Weaning occurred without
      registration of the mare of each offspring, resulting in a failure to identify
      either the mare or the sire of each foal. Animals were typed using 12
      microsatellite systems and four biochemical polymorphisms in order to determine
      the paternity/maternity of each foal. We used the CERVUS program to evaluate the
      parentage of each offspring. It was possible to determine maternity in eight
      cases, and paternity in all of them. We concluded that this set of codominant
      markers analyzed following a likelihood-based approach included in the CERVUS
      package, are useful tools to solve parentage assignments in domestic horses.

PMID- 17524056
TI  - A case of fatal intoxication from metformin.
AB  - A case of fatal intoxication from metformin is presented. The decedent was an
      obese 58-year-old-woman with type II diabetes, in whom severe lactic acidosis
      secondary to metformin accumulation was precipitated by acute renal failure. She
      had been on metformin 500 mg twice a day. Postmortem blood was deproteinated with
      acetonitrile, washed with dichloromethane, and the resulting supernatant injected
      into high-performance liquid chromatography system. Separation was performed on a
      analytical 125 x 4 mm i.d. RP-8 column. The wavelength was set at 235 nm. The
      mobile phase was acetonitrile (40%), sodium lauryl sulfate, and sodium dihydrogen
      phosphate adjusted to pH 5.1 (60%) at a flow rate of 1.0 mL/min. The
      concentration of metformin in postmortem blood was 77.3 microg/mL. The
      qualitative result was also confirmed by LC/APCI/MS/MS analysis.

PMID- 17524057
TI  - Pericardial lipoma: an autopsy case and review of the literature.
AB  - Postmortem examination performed on a 70-year-old man revealed a thinly
      encapsulated, ovoid, large mass in the right hemithorax. The tumor was attached
      with its pedicle to the atrioventral pericardium and adjoined the diaphragm with
      compression of the right lower lobe of the lung. There was no adhesion between
      the tumor and the surrounding organs. Light microscopy showed a lipoma consisting
      of mature adipose tissue, and no malignancy was found.

PMID- 17524058
TI  - Agonal sequences in a filmed suicidal hanging: analysis of respiratory and
      movement responses to asphyxia by hanging.
AB  - The forensic literature on the pathophysiology of human hanging is still limited.
      Therefore, forensic pathologists often feel uncomfortable when confronted with
      related questions. Here presented is the filmed suicidal hanging of a 37-year-old
      man. This recording allows a unique analysis of agonal movement sequences: loss
      of consciousness (13 sec), convulsions (15 sec), decortication rigidity (21 sec),
      decerebration rigidity (46 sec), second decortication rigidity (1 min 11 sec),
      loss of muscle tone, (1 min 38 sec) and last isolated muscle movement (4 min 10
      sec). As for respiratory responses, very deep respiratory attempts started at 20
      sec. Respiratory movements progressively decreased and completely stopped at 2
      min. Despite the fact that extending the presented data on all cases of hanging
      asphyxia would be a mistake, this case gives a very interesting insight into
      movement and respiratory response to asphyxia by hanging.

PMID- 17524059
TI  - Failure of anthropometry as a facial identification technique using high-quality
      photographs.
AB  - Anthropometry can be used in certain circumstances to facilitate comparison of a
      photograph of a suspect with that of the potential offender from surveillance
      footage. Experimental research was conducted to determine whether anthropometry
      has a place in forensic practice in confirming the identity of a suspect from a
      surveillance video. We examined an existing database of photographic lineups,
      where one video image was compared against 10 photographs, which has previously
      been used in psychological research. Target (1) and test (10) photos were of high
      quality, although taken with a different camera. The anthropometric landmarks of
      right and left ectocanthions, nasion, and stomion were chosen, and proportions
      and angle values between these landmarks were measured to compare target with
      test photos. Results indicate that these measurements failed to accurately
      identify targets. There was also no indication that any of the landmarks made a
      better comparison than another. It was concluded that, for these landmarks, this
      method does not generate the consistent results necessary for use as evidence in
      a court of law.

PMID- 17524060
TI  - Gunshot residue in Chicago police vehicles and facilities: an empirical study.
AB  - Suspects in shooting investigations in Chicago are routinely transported in
      department vehicles and detained in department facilities prior to gunshot
      residue (GSR) evidence collection. The GSR test results are used to associate the
      suspect with primary exposure to GSR. The potential for these vehicles and
      facilities being sources of secondary GSR contamination needed to be determined.
      A total of 201 samples were collected from randomly selected vehicles and
      detention facilities. The sampling collected trace materials from surfaces that
      suspects' hands may contact during the arrest process. These samples were
      examined for the presence of GSR particles using scanning electron microscopy.
      Upon completion of the automated analysis, those particles that met an initial
      GSR screening criterion were relocated and reanalyzed. The locations where GSR
      particles were recovered allowed us to make recommendations to the Chicago Police
      Department with regard to transporting and detaining these suspects. The low
      number of GSR particles recovered suggests that the potential for secondary
      contamination, although present, is relatively low.

PMID- 17524061
TI  - Bioinformatics and human identification in mass fatality incidents: the world
      trade center disaster.
AB  - Victim identification initiatives undertaken in the wake of Mass Fatality
      Incidents (MFIs) where high-body fragmentation has been sustained are often
      dependent on DNA typing technologies to complete their mandate. The success of
      these endeavors is linked to the choice of DNA typing methods and the
      bioinformatic tools required to make the necessary associations. Several
      bioinformatic tools were developed to assist with the identification of the
      victims of the World Trade Center attacks, one of the most complex incidents to
      date. This report describes one of these tools, the Mass Disaster Kinship
      Analysis Program (MDKAP), a pair-wise comparison software designed to handle
      large numbers of complete or partial Short Tandem Repeats (STR) genotypes, and
      infer identity of, or biological relationships between tested samples. The
      software performs all functions required to take full advantage of the
      information content of processed genotypic data sets from large-scale MFIs,
      including the collapse of victims data sets, remains re-association, virtual
      genotype generation through gap-filling, parentage trio searching, and a
      consistency check of reported/inferred biological relationships within families.
      Although very few WTC victims were genetically related, the software can detect
      parentage trios from within a victim's genotype data set through a
      nontriangulated approach that screens all possible parentage trios. All software
      inferred relationships from WTC data were confirmed by independent statistical
      analysis. With a 13 STR loci complement, a fortuitous parentage trio (FPT)
      involving nonrelated individuals was detected. Additional STR loci would be
      required to reduce the risk of an FPT going undetected in large-scale MFIs
      involving related individuals among the victims. Kinship analysis has proven
      successful in this incident but its continued success in larger scale MFIs is
      contingent on the use of a sufficient number of STR loci to reduce the risk of
      undetected FPTs, the use of mtDNA and Y-STRs to confirm parentage and of
      bioinformatics that can support large-scale comparative genotyping schemes
      capable of detecting parentage trios from within a group of related victims.

PMID- 17524062
TI  - Sudden cardiac death due to giant cell inflammatory processes.
AB  - Granulomatous inflammation of the myocardium may occur in a number of systemic
      disease processes including those with infectious etiologies such as fungal,
      mycobacterial and parasitic infections, as well as hypersensitivity reactions,
      and rarely autoimmune disorders. In many of these disorders, giant cells are
      components of the inflammatory infiltrate. Systemic granulomatous processes of
      unknown pathogenesis, most notably sarcoidosis, may also be associated with
      involvement of the myocardium. Occasionally, these disorders are associated with
      sudden death due to pathologic involvement of the heart. In contrast, giant cell
      myocarditis, also known as idiopathic myocarditis, a rare, frequently fulminant
      and fatal disorder of unknown etiology, is isolated to the heart and lacks
      systemic involvement. This disorder is most commonly diagnosed at autopsy. We
      present two cases in which sudden death resulted from a giant cell inflammatory
      process affecting the myocardium. Both individuals lacked antemortem diagnoses
      and collapsed at their respective places of employment. These cases compare and
      contrast the clinical and pathologic issues involved in the differential
      diagnoses of the subgroup of sudden cardiac deaths resulting from giant cell
      inflammatory processes that affect the myocardium, as well as the value of
      histologic examination and immunohistochemical studies.

PMID- 17524063
TI  - Fourier-transformed infrared breath testing after ingestion of technical alcohol.
AB  - The study aim was to evaluate the feasibility of a Fourier-transformed infrared
      (FT-IR) analyzer for out-of-laboratory use by screening the exhalations of
      inebriated individuals, and to determine analysis quality using common breath
      components and solvents. Each of the 35 inebriated participants gave an
      acceptable sample. Because of the metabolism of 2-propanol, the subjects exhaled
      high concentrations of acetone in addition to ethanol. Other volatile ingredients
      of technical ethanol products (methyl ethyl ketone, methyl isobutyl ketone, and 2
      propanol) were also detected. The lower limits of quantification for the analyzed
      components ranged from 1.7 to 12 microg/L in simulated breath samples. The bias
      was +/-2% for ethanol and -11% for methanol. Within-day and between-day
      coefficients of variation were <1% for ethanol and <4% for methanol. The bias of
      ethanol and methanol analyses due to coexisting solvents ranged from -0.8 to
      +2.2% and from -5.6 to +2.9%, respectively. The FT-IR method proved suitable for
      use outside the laboratory and fulfilled the quality criteria for analysis of
      solvents in breath.

PMID- 17524064
TI  - Expedited, chemically enhanced sperm cell recovery from cotton swabs for rape kit
      analysis.
AB  - This report focuses on the development of a method for chemically induced
      enhancement of cell elution and recovery from cotton swabs. The method exploits
      the exclusive use of detergents for intact cell removal, and can be utilized in
      conjunction with, or to circumvent, conventional differential extraction (DE).
      Samples treated with Sarkosyl (54.4 +/- 1.8%) and sodium dodecyl sulfate (SDS)
      (78.5 +/- 0.7%) yielded higher sperm cell recoveries than a conventional DE
      buffer (39.4 +/- 2.1%). The results indicated that the choice of detergent
      affected sperm cell yield, with anionic detergents having the greatest effect.
      Storage time of samples affected the concentration of detergent required for
      optimal sperm cell recovery, longer times requiring increased detergent
      concentrations. In addition, the extent of sperm cell lysis by proteinase K
      digestion was evaluated. The results indicate that the exclusive use of SDS
      enhances the release of sperm and epithelial cells from a cotton swab as compared
      with DE buffer, providing for a more effective DNA analysis.

PMID- 17524065
TI  - Necrotizing fasciitis: manifestations, microbiology and connection with black tar
      heroin.
AB  - A 10-year review of records of the King County Medical Examiner's Office found 87
      deaths due to necrotizing fasciitis and related necrotizing soft tissue
      infections. In 64 of these cases there were sufficient details to provide an
      analysis of the manifestations, microbiology, and source of infection. One half
      (32) of the cases were due to injection of black tar heroin, the nearly exclusive
      form of heroin in the Northwest United States. Of those due to black tar
      injection, 24 were clostridial infections with various species represented, eight
      of which were Clostridium sordellii. Of the 32 cases not associated with drug
      injection, streptococcal species predominated, with Streptococcus pyogenes
      isolated in 14 cases. Only three of 32 cases not associated with injection drug
      use were clostridial infections. These differences were statistically
      significant. Staphylococcus aureus was isolated from 14 cases; two were
      methicillin-resistant strains. Overall, 28 of the 64 cases were polymicrobial
      infections, 15 due to black tar injection and 13 not associated with drug
      injection. This study supports the conclusion that necrotizing fasciitis due to
      black tar heroin injection is predominantly a clostridial disease, and in this
      way differs significantly from necrotizing fasciitis due to other causes.

PMID- 17524067
TI  - Region specific patellar tendon hypertrophy in humans following resistance
      training.
AB  - AIM: To examine if cross-sectional area (CSA) differs along the length of the
      human patellar tendon (PT), and if there is PT hypertrophy in response to
      resistance training. METHODS: Twelve healthy young men underwent baseline and
      post-training assessments. Maximal isometric knee extension strength (MVC) was
      determined unilaterally in both legs. PT CSA was measured at the proximal-, mid-
      and distal PT level and quadriceps muscle CSA was measured at mid-thigh level
      using magnetic resonance imaging. Mechanical properties of the patellar tendons
      were determined using ultrasonography. Subsequently, subjects performed 12 weeks
      of heavy resistance knee extension training with one leg (Heavy-leg), and light
      resistance knee extension training with the other leg (Light-leg). RESULTS: The
      MVC increased for heavy-leg (15 +/- 4%, P < 0.05), but not for light-leg (6 +/-
      4%). Quadriceps CSA increased in heavy-legs (6 +/- 1%, P < 0.05) while unchanged
      in light-legs. Proximal PT CSA (104 +/- 4 mm(2)) was smaller than the mid-tendon
      CSA (118 +/- 3 mm(2)), which again was smaller than distal tendon CSA (127 +/- 2
      mm(2), P < 0.05). Light-leg PT CSA increased by 7 +/- 3% (P < 0.05) at the
      proximal tendon level, but was otherwise unchanged. Heavy-leg PT CSA increased at
      the proximal and distal tendon levels by 6 +/- 3% and 4 +/- 2% respectively (P <
      0.05), but was unchanged at the mid tendon level. PT stiffness increased in heavy
      legs (P < 0.05) but was unchanged in light-legs. Modulus remained unchanged in
      both legs. CONCLUSIONS: To our knowledge, this study is the first to report
      tendon hypertrophy following resistance training. Further, the data show that the
      human PT CSA varies along the length of the tendon.

PMID- 17524066
TI  - Separation of early afterdepolarizations from arrhythmogenic substrate in the
      isolated perfused hypokalaemic murine heart through modifiers of calcium
      homeostasis.
AB  - AIMS: We resolved roles for early afterdepolarizations (EADs) and transmural
      gradients of repolarization in arrhythmogenesis in Langendorff-perfused
      hypokalaemic murine hearts paced from the right ventricular epicardium. METHODS:
      Left ventricular epicardial and endocardial monophasic action potentials (MAPs)
      and arrhythmogenic tendency were compared in the presence and absence of the L
      type Ca(2+) channel blocker nifedipine (10 nm-1 microm) and the calmodulin kinase
      type II inhibitor KN-93 (2 microm). RESULTS: All the hypokalaemic hearts studied
      showed prolonged epicardial and endocardial MAPs, decreased epicardial
      endocardial APD(90) difference, EADs, triggered beats and ventricular tachycardia
      (VT) (n = 6). In all spontaneously beating hearts, 100 (but not 10) nm nifedipine
      reduced both the incidence of EADs and triggered beats from 66.9 +/- 15.7% to
      28.3 +/- 8.7% and episodes of VT from 10.8 +/- 6.3% to 1.2 +/- 0.7% of MAPs (n =
      6 hearts, P < 0.05); 1 microm nifedipine abolished all these phenomena (n = 6).
      In contrast programmed electrical stimulation (PES) still triggered VT in six of
      six hearts with 0, 10 and 100 nm but not 1 microm nifedipine. 1 microm nifedipine
      selectively reduced epicardial (from 66.1 +/- 3.4 to 46.2 +/- 2.5 ms) but not
      endocardial APD(90), thereby restoring DeltaAPD(90) from -5.9 +/- 2.5 to 15.5 +/-
      3.2 ms, close to normokalaemic values. KN-93 similarly reduced EADs, triggered
      beats and VT in spontaneously beating hearts to 29.6 +/- 8.9% and 1.7 +/- 1.1%
      respectively (n = 6) yet permitted PES-induced VT (n = 6), in the presence of a
      persistently negative DeltaAPD(90). CONCLUSIONS: These findings empirically
      implicate both EADs and triggered beats alongside arrhythmogenic substrate of
      DeltaAPD(90) in VT pathogenesis at the whole heart level.

PMID- 17524068
TI  - Relative risk for cancer in mucous membrane pemphigoid associated with antibodies
      to the beta4 integrin subunit.
AB  - BACKGROUND: Mucous membrane pemphigoid (MMP) is a mucocutaneous vesiculobullous
      autoimmune disease characterized by autoantibodies to components of the basement
      membrane zone (BMZ). Recently, it has been reported that patients with MMP who
      have autoantibodies to laminin 5, known as anti-epiligrin cicatricial pemphigoid
      (AECP) have a high incidence of malignancy. OBJECTIVE: The purpose of this study
      was to determine the association between malignancy and MMP in patients with
      antibodies to beta4 integrin. METHODS: The incidence of cancer was studied in 79
      patients with MMP and/or ocular cicatricial pemphigoid (OCP) who had antibodies
      to human beta4 integrin subunit. In each patient, the diagnosis was made by
      histology and confirmed by immunopathology of affected tissues. It was compared
      to the expected incidence, for age- and gender-matched individuals, in the
      National Cancer Institute's Surveillance, Epidemiology and End Results (NCISEER)
      database. RESULTS: Of 79 patients, 3 had cancer. The relative risk (RR) for
      cancer in patients with MMP and/or OCP, with autoantibodies to human beta4
      integrin subunit was 0.29 (95% CI 0.62-8.77). The expected number in the NCISEER
      database was 10.37. This difference was statistically significant (P < 0.01).
      CONCLUSION: This incidence of cancer in MMP/OCP patients, with antibodies to
      human beta4 integrin subunit is considerably lower than expected. Preliminary
      observations in this and other studies suggest that serological subsets of MMP,
      based on antigen reactivity, have a different clinical course, prognosis and
      associations with cancer.

PMID- 17524069
TI  - Cutaneous phaeohyphomycosis due to Cladophialophora bantiana in an
      immunocompetent patient.
AB  - We report the case of a 56-year-old Chinese woman with phaeohyphomycosis. She
      presented with a 4-year history of a recurring erythematous plague initially
      diagnosed as chromoblastomycosis on histopathological examination. Surgical
      excision was performed when the lesion recurred despite intial treatment response
      to itraconazole. Tissue cultures of the surgical specimen grew Cladophialophora
      bantiana. Treatment with terbinaffine post surgery was instituted with no
      recurrence of the lesion to date. Cutaneous phaeohyphomycosis caused by
      Cladophialophora bantiana is rare and this case highlights the clinical
      presentation, laboratory findings and treatment of this infection.

PMID- 17524070
TI  - Focal acral hyperkeratosis.

PMID- 17524072
TI  - Transvenous renal biopsy of a kidney transplant in a patient with a suspected
      bleeding disorder.

PMID- 17524073
TI  - A comparison of long-term survivals of simultaneous pancreas-kidney transplant
      between African American and Caucasian recipients with basiliximab induction
      therapy.
AB  - African Americans (AA) have traditionally been thought to have higher immunologic
      risk than Caucasians (CA) for rejection and allograft loss. The impact of
      ethnicity on the outcome of simultaneous pancreas-kidney (SPK) transplant with
      basiliximab induction has not been reported. In this study, we retrospectively
      analyze the long-term results of 36 AA and 55 CA recipients of primary SPK. The
      actual patient survival rates of AA and CA groups were 91.7% vs. 90.1% at 1 year,
      93.3% vs. 88.1% at 3 years, and 94.4% vs. 83.3% at 5 years. The actual kidney
      survival of AA and CA were 91.7% vs. 89.1% at 1 year, 90% vs. 81% at 3 years, and
      83.3% vs. 75% at 5 years. The actual pancreas survival of AA and CA were 88.9%
      vs. 85.5% at 1 year, 83.3% vs. 78.6% at 3 years and 72.2% vs. 70.8% at 5 years.
      Death-censored analyses also found no difference in pancreas and kidney graft
      survival rates over 5 years. Higher rejection rate, but the same low CMV
      infection, and comparable quality of graft function were noted in AA group. AA
      may not have worse long-term outcomes than CA recipients of SPK with basiliximab
      induction and tacrolimus (TAC), mycophenolate acid (MFA) and steroid maintenance
      immunotherapy.

PMID- 17524074
TI  - Value of posttransplant antibody tests in the evaluation of patients with renal
      graft dysfunction.
AB  - Posttransplant HLA antibodies correlate with C4d positive rejection and decreased
      graft survival. However, the diagnostic value of various antibody tests in the
      management of patients presenting with graft dysfunction is uncertain. Whether
      all or some patients should be tested, how often, what antibodies to test for and
      how to interpret results in presensitized or transfused patients, are issues
      still unresolved. We tested for HLA and non-HLA antibodies by flow cytometry
      assays in 103 consecutive patients with graft dysfunction. The results show that:
      (1) C4d positive rejection was diagnosed in 75% of patients who developed
      posttransplant HLA antibodies, but only in 2% in antibody negative patients. (2)
      The correlation existed for donor specific IgG antibodies but not for IgM or
      nondonor specific IgG antibodies. (3) Weak antibody reactivity required
      confirmation by alternative testing as there were false positive results. (4)
      Posttransplant transfusions did not induce de novo HLA antibodies. (5) Negative
      antibody results were unlikely to turn positive after several months of follow
      up. (6) Antibodies to the angiotensin II type 1 receptor, HLA-DP and MICA did not
      correlate with C4d+ rejection. We conclude that testing for posttransplant HLA
      antibodies is critical in narrowing the diagnostic alternatives in patients with
      graft dysfunction.

PMID- 17524075
TI  - Genitourinary tuberculosis after renal transplantation-a report of three cases
      with a good clinical outcome.
AB  - Tuberculosis (TB) continues to be a major opportunistic infection after renal
      transplantation especially in the tropical countries. The risk of TB in renal
      transplant recipients is reported to be 20-74 times higher than that in the
      general population. Genitourinary TB that occurs after renal transplantation in
      uncommon and appears to present differently than genitourinary TB in the non
      transplant population. An increased risk of graft rejection and graft loss has
      been reported. We report three cases of genitourinary TB in renal transplant
      recipients, all of whom had a good clinical outcome and a review of published
      literature.

PMID- 17524076
TI  - Outcomes of kidneys from donors after cardiac death: implications for allocation
      and preservation.
AB  - Although donation after cardiac death (DCD) kidneys have a high incidence of
      delayed graft function (DGF) and have been considered marginal, no tool for
      stratifying risk of graft loss nor a specific policy governing their allocation
      exist. We compared outcomes of 2562 DCD, 62,800 standard criteria donor (SCD) and
      12,812 expanded criteria donor (ECD) transplants reported between 1993 and 2005,
      and evaluated factors associated with risk of graft loss and DGF in DCD kidneys.
      Donor age was the only criterion used in the definition of ECD kidneys that
      independently predicted graft loss among DCD kidneys. Kidneys from DCD donors <50
      had similar long-term graft survival to those from SCD (RR 1.1, p = NS). While
      DGF was higher among DCD compared to SCD and ECD, limiting cold ischemia (CIT) to
      <12 h decreased the rate of DGF 15% among DCD <50 kidneys. These findings suggest
      that DCD <50 kidneys function like SCD kidneys and should not be viewed as
      marginal or ECD, and further, limiting CIT <12 h markedly reduces DGF.

PMID- 17524077
TI  - The identity of innate immune activators in organ transplantation: origins from
      within or exterior to the host?

PMID- 17524078
TI  - Lung transplant metalloproteinase levels are elevated prior to bronchiolitis
      obliterans syndrome.
AB  - Parenchymal disease in the allograft lung is associated with interstitial
      remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent
      studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans
      syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the
      posttransplant period and may be preceded by episodes of acute rejection or
      infection, which are associated with interstitial remodeling, we examined MMP
      profiles in allograft bronchoalveolar lavage (BAL) fluid in the early
      posttransplant period (preceding BOS). Gelatin zymography, protein array analysis
      and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8,
      MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable
      patients, or those with infection or rejection compared to BAL fluid from normal
      volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and
      was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9
      and TIMP-1 in the first 2 years posttransplant appear to be associated with lung
      transplantation itself, and not infection or rejection. These data suggest that
      ongoing and clinically silent MMP activity could perpetuate progressive disease
      in the allograft lung.

PMID- 17524079
TI  - Graft selection algorithm based on congestion volume for adult living donor liver
      transplantation.
AB  - A major concern in adult-to-adult living donor liver transplantation is the
      selection of graft type; that is, is it is better to use the right lobe with or
      without the middle hepatic vein (MHV)? This choice has a considerable impact on
      donor safety, vascular reconstruction and graft function in the recipient. To
      facilitate making an appropriate choice, on the basis of a preliminary study (n =
      17), we herein propose a graft selection algorithm using three parameters: graft
      to-recipient body weight ratio (GRWR), percentage remnant liver volume (%RLV) and
      estimated congestion ratio (ECR). The algorithm was evaluated with 50 consecutive
      cases with respect to postoperative liver function of donors and recipients and
      survival of recipients. Postoperative recovery was comparable between the two
      groups (p = NS). The overall cumulative 18-month survival rate was 86.7% for the
      'with MHV graft group', and 76.1% for the gwithout MHV graft grouph (p = NS). For
      41 cases (82%), graft types were chosen according to the algorithm, whereas the
      remaining 9 cases (18%) needed detailed discussion of donor, recipient and
      operative factors. In conclusion, we constructed a graft selection algorithm
      based on congestion volume, which will contribute to objective graft-type
      selection in adult-to-adult LDLT.

PMID- 17524080
TI  - Perceived transparency and fairness of the organ allocation system and
      willingness to donate organs: a national study.
AB  - The influence of perceptions of organ allocation on willingness to donate organs
      is unclear. We performed a national study assessing the relation of public
      perceptions of organ allocation to willingness to donate organs, and we assessed
      the contribution of beliefs regarding discrimination in health care to observed
      associations. Among 845 participants, a majority (65%) reported that they less
      than "mostly" understand allocation, and most (71%) reported that they believe
      allocation is "unfair" or are "unsure" of its fairness. Participants reporting
      less understanding were less willing to donate (56%) than persons reporting
      greater understanding (67%) (p < 0.01). Participants believing allocation is
      "unfair" or who are "unsure" about fairness were less willing to donate (54%)
      than persons believing allocation is "fair" (68%) (p < 0.01). Associations were
      stronger among certain demographic subgroups. Participants with the least
      favorable perceptions of allocation were more likely than their counterparts to
      believe that race and income discrimination occur in transplantation and to
      believe that they personally experienced income discrimination in health care.
      Adjustment for these beliefs partially attenuated associations between
      perceptions regarding allocation and willingness to donate. Interventions
      enhancing transparency and perceived fairness of organ allocation may improve
      willingness to donate, particularly if they address concerns regarding
      discrimination in transplantation and health care.

PMID- 17524081
TI  - Transfusion medicine history illustrated. Technology transfer: the DeBakey roller
      pump.

PMID- 17524082
TI  - The effect of interruption of agitation on in vitro measures of platelet
      concentrates in additive solution.
AB  - BACKGROUND: Interruption of agitation results in lower in vitro quality of
      platelet concentrates (PCs). The rates at which the deleterious effects occur,
      however, are unknown. Therefore, in vitro parameters of PCs in additive solution
      (AS) during various periods without agitation have been investigated. STUDY
      DESIGN AND METHODS: PCs from five buffy coats in AS (Composol, Fresenius
      HemoCare) were white cell (WBC)-reduced by filtration. Four PCs were pooled and
      divided to obtain paired samples. Beginning immediately after processing, three
      PCs were stored without agitation and placed on an agitator after 16, 20, and 24
      hours. The fourth PC was agitated throughout storage and served as reference (n =
      10 paired experiments). RESULTS: pH(37 degrees C) on Day 7 was greater than 6.8
      in reference PCs, and in PCs that were not agitated for 16 hours, longer
      interruption resulted in lower pH values. During interruption of agitation,
      metabolic rates were significantly higher in the study groups: glucose
      consumption was 12.5 +/- 1.6 micromol per 10(11) platelets (PLTs) per hour in PCs
      during the first 24 hours without interruption versus 2.0 +/- 0.4 micromol per
      10(11) PLTs per hour in the reference group (p < 0.01). Lactate formation was
      24.7 +/- 4.2 versus 3.9 +/- 0.4 micromol per 10(11) PLTs per hour in the above
      mentioned groups, respectively (p < 0.01). Once replaced on the agitator, the
      metabolic rates lowered, but remained significantly elevated during consecutive
      storage days compared to the reference. CONCLUSION: WBC-reduced PCs in Composol
      AS may experience 16 hours without agitation with no permanent effects on in
      vitro measures compared to reference units. During interruption of agitation,
      glucose and lactate metabolism is elevated, resulting in lower pH values in the
      subsequent storage period.

PMID- 17524083
TI  - Storage of platelets in a novel additive solution (M-sol), which is prepared by
      mixing solutions approved for clinical use that are not especially for platelet
      storage.
AB  - BACKGROUND: To reduce adverse reactions due to platelet (PLT) transfusion,
      medical solutions on the market, such as saline and ACD-A, are used to replace
      the plasma of PLT concentrates in Japan; however, they are not strongly
      preservative. Here, an attempt was made to develop a novel additive solution (M
      sol) having the ability to preserve PLTs stably, with only approved solutions for
      clinical use. STUDY DESIGN AND METHODS: M-sol is a mixture of solutions for
      medical use, which consists of 77 mmol per L NaCl, 3 mmol per L KCl, 1 mmol per L
      CaCl2, 21 mmol per L Na acetate, 15 mmol per L glucose, 9.4 mmol per L Na3
      citrate, 4.8 mmol per L citric acid, 44 mmol per L NaHCO3, and 1.6 mmol per L
      MgSO4. The in vitro variables of PLTs stored in M-sol, Seto-sol, PASIIIM, or 100
      percent plasma were compared during 14 days of storage. RESULTS: The in vitro
      parameters (pH, P-selectin, %hypotonic shock response, %disk, mean PLT volume,
      aggregability) of PLTs were better maintained in M-sol containing 3 percent
      plasma than in 100 percent plasma, PASIIIM with 31 percent plasma, and Seto-sol
      with 3 percent plasma during 14 days of storage. CONCLUSION: The 2-week storage
      of PLTs in M-sol is feasible in terms of the in vitro PLT function. Our results
      here show that the additive solution, with a high ability to preserve PLTs, can
      be prepared by mixing solutions approved for clinical use that are not
      specifically for PLT storage.

PMID- 17524084
TI  - Red blood cell (RBC) age at collection and storage influences RBC membrane
      associated carbohydrates and lectin binding.
AB  - BACKGROUND: Membrane-associated carbohydrate changes act as signals for removal
      of senescent and damaged red blood cells (RBCs) from the circulation and could
      play a role in the RBC storage lesion and RBC survival after transfusion. In this
      study, a panel of lectins was used to investigate the expression of carbohydrates
      on RBCs that had been separated before storage into young and old RBCs. STUDY
      DESIGN AND METHODS: Leukodepleted RBCs were separated before storage into young
      and old RBCs (n = 9 paired units) by centrifugation and sampled at nominated time
      points during 42 days of storage. Changes to carbohydrate expression at the RBC
      membrane during storage were determined by flow cytometry with a panel of
      fluorescein-labeled lectins. RESULTS: Old RBCs showed lower fluorescence
      intensity throughout storage, suggesting reduced binding of lectins compared to
      young RBCs. Progressively increased binding of lectins specific for galactose and
      N-acetylglucosamine residues was observed during storage of young and old RBCs.
      CONCLUSION: Changes to lectin binding during storage of RBCs suggest that
      significant changes occur to the carbohydrate structures at the RBC membrane.
      These findings provide further insight into the mechanisms of the RBC storage
      lesion and potential influence on RBC survival after transfusion.

PMID- 17524085
TI  - Differences in functional activity and antigen expression of granulocytes primed
      in vivo with filgrastim, lenograstim, or pegfilgrastim.
AB  - BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is known to affect
      functional activity and antigen expression of neutrophil granulocytes. Beside
      nonglycosylated filgrastim and glycosylated lenograstim, pegylated filgrastim
      (pegfilgrastim) has recently been introduced for single administration into
      clinical use. STUDY DESIGN AND METHODS: Here, granulocytes from 27 patients with
      nonmyeloid malignancies were compared functionally (migration, reactive oxygen
      species production, and G-CSF serum levels) and phenotypically (cell surface
      antigen expression) before and after G-CSF administration. RESULTS: After
      exposure to G-CSF, chemotaxis was reduced significantly in the filgrastim group.
      Immunophenotypically, in vivo G-CSF-primed granulocytes were more mature in the
      lenograstim than in the filgrastim and to lesser extent in the pegfilgrastim
      groups as shown by the expression profile for CD11b, CD14, and CD16. Of note, G
      CSF serum levels were similar among the groups. CONCLUSION: Our data suggest that
      granulocytes exposed to glycosylated G-CSF in vivo seem to resemble more closely
      their steady-state phenotype than after treatment with nonglycosylated and to
      lesser extent pegylated G-CSF.

PMID- 17524086
TI  - Use of therapeutic plasma exchange in the management of acute hemorrhagic
      leukoencephalitis: a case report and review of the literature.
AB  - BACKGROUND: Acute hemorrhagic leukoencephalitis (AHLE) is a rare, fatal, central
      nervous demyelinating disease characterized by a rapid fulminant clinical course.
      Successful management requires early diagnosis, aggressive management of cerebral
      edema, and immunosuppression. Therapeutic plasma exchange (TPE) is infrequently
      used and commences after initial management fails. CASE REPORT: A 31-year-old man
      presented with right arm weakness, whose symptoms rapidly progressed to
      hemiplegia and aphasia. The patient was initially managed with
      glucocorticosteroids. Decompressive craniotomy and brain biopsies were performed
      when his intracranial pressure increased. Brain biopsy findings were consistent
      with AHLE. Mycoplasma pneumonia immunoglobulin G and immunoglobulin M serologies
      revealed recent infection. Despite surgical and medical management, he
      decompensated on Day 11, and TPE was initiated. The patient received a total of
      10 TPE treatments. On the fourth day of TPE treatment, he was extubated. Twenty
      one days after TPE began, he was ambulating with near normal muscle strength and
      was discharged. Four months after initial presentation, the patient has normal
      strength and is working full-time. CONCLUSIONS: AHLE has a fulminant course
      requiring accurate and rapid diagnosis. Successful therapy requires aggressive
      management of intracranial pressure and immunosuppression. Two other reports of
      AHLE document successful management with TPE. Each of these patients survived
      with minimal neurologic impairments. Given the likely immune-mediated nature of
      this disease, combined treatment of steroids, surgery, and TPE may lead to
      shorter hospital stays and improved neurologic outcomes. Clinical studies are
      needed to further study the effect of TPE on neurologic outcome in AHLE.

PMID- 17524087
TI  - Evaluation of a new apheresis system for the collection of leukoreduced single
      donor platelets.
AB  - BACKGROUND: The Fresenius COM.TEC cell separator is a new device for producing
      white cell concentrates (WBCs) and leukoreduced single-donor platelet
      concentrates (SDPs) and performing therapeutic cytapheresis and plasmapheresis
      that might replace the Fresenius systems AS104 and AS.TEC 204. This novel
      system's performance was evaluated for producing leukoreduced SDPs. STUDY DESIGN
      AND METHODS: In an investigational phase, each of 200 donors underwent
      plateletpheresis with the AS.TEC 204 and the COM.TEC systems. The collection
      efficiency (CE) and WBC contamination of the different techniques were compared.
      After some hard- and software modifications, the system was evaluated in an
      additional 800 procedures in the confirmatory phase. RESULTS: In the
      investigational phase, the CE of the COM.TEC device was increased significantly
      in comparison to the AS.TEC 204 device's CE (by 45 +/- 32% when collecting 1 unit
      of platelets [PLTs] and 1 unit of fresh-frozen plasma and by 43 +/- 42% when
      collecting only 1 unit of PLTs). Although all AS.TEC products proved to be
      leukoreduced, 2 percent of the COM.TEC procedures led to PLT concentrates
      containing more than 1 x 10(6) WBCs. In the confirmatory phase, all 1300 products
      from 800 COM.TEC procedures proved to be leukoreduced. Furthermore, the CE
      increased significantly from 53.5 +/- 4.6 percent in the investigational phase to
      55.5 +/- 4.9 percent (p < 0.001) in the confirmatory phase. CONCLUSIONS: These
      data suggest that the new COM.TEC system offers a significantly and importantly
      improved CE in plateletpheresis procedures in comparison to the AS.TEC system. In
      the final version, the PLT products collected with this system fulfill the most
      stringent criteria for leukoreduced PLTs. This aim was achieved without
      additional filtration steps and thus without filtration-related PLT loss.

PMID- 17524088
TI  - Donor retention as a function of donor reactions to whole-blood and automated
      double red cell collections.
AB  - BACKGROUND: Although reactions to whole-blood (WB) donation are known to decrease
      donor retention, potential effects of reactions to automated double red cell
      (2RBC) donation upon retention have not been investigated. STUDY DESIGN AND
      METHODS: The authors investigated effects of donor status (first-time,
      experienced) and reactions (absent, present) upon retention of all male
      allogeneic WB and 2RBC donors (n = 45,296) donating within the American Red Cross
      Central Ohio Region during a 12-month period. Donor age, race, and status (first
      time, experienced); phlebotomist's reaction rating; and phlebotomy procedure (WB,
      2RBC) were collected for the initial donation by each donor. Dates of any
      donation attempts in the 12 months starting from the donor's first eligible date
      after the initial donation were also collected. RESULTS: On average, WB donors
      were less likely to react and more likely to donate again and returned more
      quickly to donate than 2RBC donors, even after accounting for differential delays
      in eligibility. Reactions decreased the likelihood of repeat donation among all
      first-time donors regardless of initial phlebotomy procedure. Among experienced
      donors, however, reactions depressed retention of WB donors by 27.6 percent,
      whereas reactions lowered retention of 2RBC donors by just 3.6 percent.
      CONCLUSION: Although 2RBC donors were more likely to react, first-time 2RBC
      donors were no more affected by reactions than first-time WB donors. Experienced
      WB donors suffered a larger drop in retention as a function of reactions, in
      fact, than did experienced donors who gave 2RBC donations. Potential reasons for
      this data pattern require further investigation.

PMID- 17524089
TI  - The safety profile of automated collections: an analysis of more than 1 million
      collections.
AB  - BACKGROUND: Recent technology allows for the collection of 2-unit red cells
      (RBCs) and single-unit RBCs plus plasma or platelets (PLTs). STUDY DESIGN AND
      METHODS: With a common definition of adverse events, 1,023,682 whole-blood
      collections were evaluated and compared with 249,154 two-unit apheresis RBC
      collections, 40,870 single-apheresis RBC collections, and 90,082 apheresis PLT
      collections. RESULTS: The data show that manual whole-blood collections have a
      low incidence of moderate and severe reactions (47.1 per 10,000 collections,
      0.47%). Single-unit RBCs collected by apheresis have the same safety profile
      (37.44 per 10,000 collections, p > 0.20). Double-RBC collections by apheresis and
      plateletpheresis have a significantly lower reaction rate (15.65 per 10,000
      collections, p < 0.00005; and 14.84 per 10,000 collections, p < 0.00005,
      respectively). CONCLUSION: It is concluded that automated collections are safe or
      safer than manual whole-blood collections. There should be few concerns when
      procedures are performed according to manufacturer's instructions.

PMID- 17524090
TI  - A path analysis of intention to redonate among experienced blood donors: an
      extension of the theory of planned behavior.
AB  - BACKGROUND: The need for blood products is constant and unremitting, yet only a
      small percentage of eligible individuals answer the appeal to donate. Further,
      most new donors never return to provide a repeat donation. The ongoing need to
      attract and retain new donors has led to the examination of psychosocial factors
      that may predict the likelihood of blood donation behavior. By use of regression
      techniques, prior studies have established that elements of the Theory of Planned
      Behavior (e.g., attitude, subjective norm, personal moral norm, and perceived
      control or self-efficacy) can predict intention to donate among nondonors. STUDY
      DESIGN AND METHODS: Path analysis was used to further examine the utility of the
      Theory of Planned Behavior in predicting donation intention in a sample of 227
      experienced donors who completed an online survey. Experiential measures relating
      to previous donations, including the experience of vasovagal reactions and
      overall donor satisfaction, were added to the model. RESULTS: The final model,
      which provided an excellent fit to the data, characterized 1) three direct
      pathways from attitude, subjective norm, and self-efficacy to donation intention
      and 2) four indirect pathways, wherein self-efficacy, personal moral norm,
      vasovagal reactions, and overall donor satisfaction influence donation intention
      through attitude. In total, 65 percent of the variance in donation intention and
      50 percent of the variance in attitude is accounted for in this model.
      CONCLUSION: The Theory of Planned Behavior can be used to predict donation
      intentions among experienced donors. Further, the model's predictive utility is
      improved by considering the influence of previous donation experiences on donor
      attitudes.

PMID- 17524091
TI  - Three missense mutations, including a novel 860C>T transition, and allelic
      enhancement phenomenon associated with ABO blood subgroups A in Taiwan.
AB  - BACKGROUND: It was estimated that approximately 25 percent of Taiwanese residents
      were ABO blood group A. Many subgroups of A, however, revealed ambiguous
      serologic typing results. This study aimed to delineate the molecular basis of
      the A3, Ax, and weak A phenotypes. STUDY DESIGN AND METHODS: Serologic analyses
      including adsorption and elution assay, serum transferases activity assay, and
      saliva test were performed to determine the unique phenotypes of these samples.
      DNA sequencing and polymerase chain reaction-restriction fragment length
      polymorphism were performed to further investigate the relationships between the
      genetic characteristics and phenotypic features of these samples. RESULTS: Three
      single-nucleotide transitions (745C>T, 820G>A, and a novel 860C>T) were found in
      nine A3/A3B cases. In addition, the Ax and A3B subjects shared the same 860C>T
      mutation. This A(x) allele with 860C>T transition expressed A3B phenotype in
      A(x)/B101 heterozygote but Ax phenotype in A(x)/O01 heterozygote. This allelic
      enhancement was also observed in the weak A family with Aw05 allele, which was
      previously not found in Taiwan. CONCLUSION: This allelic enhancement phenomenon
      was prone to cause serologic discrepancy between parents and children. Genotyping
      could help us to resolve this problem. Thus, a novel mutation is reported among
      Taiwanese blood donors.

PMID- 17524092
TI  - Changes in red blood cell transfusion practice during the past two decades: a
      retrospective analysis, with the Mayo database, of adult patients undergoing
      major spine surgery.
AB  - BACKGROUND: Others have reported significant changes in red blood cell (RBC)
      transfusion practice during the past two decades during knee, hip, prostate, and
      carotid surgery. Similar data for patients undergoing major spine surgery,
      however, are not available. STUDY DESIGN AND METHODS: After institutional review
      board approval, adult patients undergoing elective major spine surgery were
      stratified into one of two transfusion-related groups: 1) 1980 to 1985 (i.e.,
      before human immunodeficiency virus screening, early practice group; n = 699) or
      2) 1995 to 2000 (i.e., late practice group; n = 610). RESULTS: Patients in the
      late practice group were older, had greater numbers of preoperative coexisting
      diseases (e.g., hypertension, cardiac dysrhythmias, coronary artery disease,
      prior myocardial infarction, diabetes mellitus, renal disease, cerebrovascular
      disease, and asthma), and were exposed to longer operations (p < 0.01 for each
      variable). Over time, allogeneic RBC administration significantly decreased,
      whereas autologous and intraoperative autotransfusion significantly increased.
      Compared to the early practice group, all perioperative Hb concentrations were
      significantly lower than the late practice group, yet no significant difference
      in major morbidity or mortality was observed between groups. CONCLUSION: In this
      retrospective analysis, significantly lower acceptable perioperative Hb
      concentrations were observed in older patients having substantially worse
      baseline comorbidity and exposed to longer major spine operations, without
      significant change in the incidence of perioperative morbidity or mortality.

PMID- 17524093
TI  - Recombinant human C1-inhibitor in the treatment of acute angioedema attacks.
AB  - BACKGROUND: Patients with hereditary C1-inhibitor deficiency have recurrent
      attacks of angioedema, preferably treated with C1-inhibitor concentrate. A
      recombinant human C1-inhibitor (rHuC1INH) was developed, derived from milk from
      transgenic rabbits. This study was undertaken to investigate the effects of
      rHuC1INH in the treatment of acute angioedema attacks in patients with a
      hereditary C1-inhibitor deficiency. STUDY DESIGN AND METHODS: Patients with
      hereditary C1-inhibitor deficiency were treated with rHuC1INH (at a dose of 100
      U/kg) within 8 hours after onset of an acute attack. Time to initiation of relief
      and time to minimal symptoms were reported by both the patient and the treating
      physician. RESULTS: Thirteen severe angioedema attacks in 9 patients with
      hereditary C1-inhibitor deficiency were treated with rHuC1INH. There was rapid
      improvement of clinical conditions for all attacks, with approximately 80 percent
      of treated patients experiencing symptom relief within 2 hours and minimal
      symptoms within 12 hours. There were no drug-related adverse events or
      immunogenic reactions to C1-inhibitor or rabbit proteins. CONCLUSION: The
      transgenically produced rHuC1INH was successfully used in the treatment of acute
      angioedema attacks in patients with hereditary C1-inhibitor deficiency.

PMID- 17524094
TI  - Cryopreservation of cellular products in a closed-bag system with an incorporated
      dimethyl sulfoxide-resistant sterile filter outside of cleanroom facilities.
AB  - BACKGROUND: Manipulations, for example, cryopreservation, of cellular
      therapeutics carried out in an open system must be performed in a class A
      environment with surrounding class B environment. To avoid cleanroom facilities,
      a new closed-bag system with an incorporated dimethyl sulfoxide-resistant sterile
      filter for cryopreservation of cellular products was evaluated at two different
      centers. STUDY DESIGN AND METHODS: A total of 44 different products (22 buffy
      coats [BCs] and 22 leukapheresis [LK] products) were split and cryopreserved in
      parallel in cleanroom facilities (Method I) and with the closed system on the
      bench of a "normal" laboratory (Method II). Viability analyzed by 7
      aminoactinomycin D staining and flow cytometric analysis and sterility of the
      products were analyzed. RESULTS: Independent of the cellular source (BC or LK),
      the median viability of CD45+ cells decreased significantly (p < 0.01) during
      cryopreservation: namely, in BCs, -15.8 percent with both methods, and in LK
      products, -5.4 percent with Method I and -4.8 percent with Method II,
      respectively. CD3+ as well as CD14+ cells exhibited a similar pattern and were
      also found significantly (p < 0.01) diminished after thawing independent of the
      handling system. For CD19+ cells, the small decrease of viability was only for
      the BC group significant (p = 0.027) when the cells had been processed with
      Method I. No bacterial contamination was detected neither in fresh products nor
      in products after cryopreservation. CONCLUSION: The closed system for
      cryopreservation of cellular products appears to be equivalent to cleanroom-based
      methods regarding cellular integrity and sterility when appropriate quality of
      sterile filters is assured.

PMID- 17524095
TI  - Characterization of mononuclear cells remaining in the leukoreduction system
      chambers of apheresis instruments after routine platelet collection: a new source
      of viable human blood cells.
AB  - BACKGROUND: The yield of white blood cells (WBCs) extracted from whole-blood
      leukoreduction filters can be affected by the storage conditions and delay before
      filtration. Platelets (PLTs) collected with apheresis instruments (Trima Accel,
      Gambro BCT) are leukoreduced during the procedure on a fluidized particle bed in
      a leukoreduction chamber (LRS chamber). In this report, the residual cell content
      of these LRS chambers was characterized to determine whether it would be a
      valuable source of viable human blood cells. STUDY DESIGN AND METHODS: The
      content of LRS chambers was eluted by gravity, and peripheral blood mononuclear
      cells (PBMNCs) were purified on a Ficoll-Paque gradient. Analyses were performed
      before and after freezing. Proportions of CD3+, CD14+, CD16+, CD19+, CD34+, and
      CD45+ cells were determined by flow cytometry. The frequency of T cells
      expressing CD4, CD8, and CD27 and of B cells expressing immunoglobulin G (IgG),
      IgM, and CD27 was also determined. RESULTS: LRS chambers held approximately 10(9)
      CD45+ cells representing the normal proportions of CD3+, CD14+, CD16+, and CD19+
      cell populations of PBMNCs. A small fraction of these CD45+ cells were CD34+CD38+
      cells (0.3 +/- 0.2%). The viability of these cells, measured before and after
      freezing, was more than 95 percent. CONCLUSION: The residual cell content of
      Trima Accel LRS chambers recovered after PLT collection is a good source of
      viable monocytes and lymphocytes. These PBMNCs, containing CD3+, CD14+, CD16+,
      CD19+, and CD34+ cells can be frozen to prepare cell banks, which opens new
      avenues for utilization in several physiologic studies or even in cellular
      therapy applications.

PMID- 17524096
TI  - Use of X-linked short tandem repeat loci in routine parentage casework.
AB  - BACKGROUND: Dealing with genetic inconsistencies in parentage testing, especially
      in motherless cases, remains a continual difficulty. STUDY DESIGN AND METHODS:
      Four difficult cases, comprising two trios and two duos, were selected from
      routine parentage testing casework. In these, relatively low combined paternity
      indices were observed as a result of few discrepant loci that were treated as
      being due to paternal mutations. An additional eight short tandem repeat (STR)
      loci along the X chromosome were studied in the alleged father and female child
      to try and help resolve these cases. RESULTS: In all four cases, the X chromosome
      haplotypes in the alleged father were different from those in the child, showing
      decisively that the alleged father could be excluded from being the biologic
      father of the child. CONCLUSION: In recent times the study of X chromosome
      haplotypes has been shown to be useful in parentage testing where the alleged
      father is absent and where only his close relatives are available for testing.
      This work demonstrates that such studies can also prove valuable in the testing
      of standard trios and duos in cases where there only a few genetic
      inconsistencies amongst the loci tested, making it difficult to distinguish
      between paternal mutations and a close relative of the alleged father being the
      biologic father.

PMID- 17524097
TI  - Frequent detection of the parvoviruses, PARV4 and PARV5, in plasma from blood
      donors and symptomatic individuals.
AB  - BACKGROUND: Plasma pools used in the manufacture of blood- and plasma-derived
      medicinal products are frequently contaminated with parvovirus B19. The presence
      of the novel human parvovirus PARV4 and a related variant PARV5 in manufacturing
      plasma pools was recently demonstrated. Another recently identified parvovirus,
      human bocavirus (HBoV), has been identified in respiratory samples from children
      with lower respiratory tract disease. STUDY DESIGN AND METHODS: Recent and
      archived manufacturing plasma pools, as well as plasma from healthy blood donors
      (individual donations; pools of 16 donations) and febrile patients, were examined
      for the presence of PARV4 and PARV5 with conventional and TaqMan polymerase chain
      reaction assays. In addition, highly sensitive assays were used to examine the
      presence of HBoV DNA in manufacturing pools. RESULTS: Of 351 recent manufacturing
      plasma pool samples, 14 (4%) tested positive for the presence of PARV4 and PARV5.
      This frequency was elevated in the archived pools. Viral loads ranged from less
      than 100 up to 4 million copies per mL plasma, with some pools containing a
      mixture of both viruses. In individual plasma samples from healthy blood donors
      and febrile patients, the frequencies of detection were 2 and 6 percent,
      respectively. No HBoV sequences were identified in manufacturing plasma pools (n
      = 167). CONCLUSION: PARV4 and PARV5 are readily detected in manufacturing plasma
      pools, test pools (constructed from 16 donations), and individual donations
      derived from healthy blood donors. The prevalence of these viruses was increased
      in plasma samples from febrile patients. Despite the use of highly sensitive
      assays for HBoV, it was not possible to identify manufacturing plasma pools
      containing HBoV sequences.

PMID- 17524098
TI  - Inactivation of parvovirus B19 in human platelet concentrates by treatment with
      amotosalen and ultraviolet A illumination.
AB  - BACKGROUND: The human erythrovirus B19 (B19) is a small (18- to 26-nm)
      nonenveloped virus with a single-stranded DNA genome of 5.6 kb. B19 is clinically
      significant and is also generally resistant to pathogen inactivation methods.
      Photochemical treatment (PCT) with amotosalen and ultraviolet A (UVA) inactivates
      viruses, bacteria, and protozoa in platelets (PLTs) and plasma prepared for
      transfusion. In this study, the capacity of PCT to inactivate B19 in human PLT
      concentrates was evaluated. STUDY DESIGN AND METHODS: B19 inactivation was
      measured by a novel enzyme-linked immunosorbent spot (ELISPOT) erythroid
      progenitor cell infectivity assay and by inhibition of long-range (up to 4.3 kb)
      polymerase chain reaction (PCR), under conditions where the whole coding region
      of the viral genome was amplified. B19-infected plasma was used to test whether
      incubation of amotosalen with virus before PCT enhanced inactivation compared to
      immediate PCT. RESULTS: Inactivation of up to 5.8 log of B19 as measured by the
      infectivity assay, or up to 6 logs as measured by PCR inhibition can be achieved
      under non-limiting conditions. Inactivation efficacy was found to increase with
      incubation prior to UVA illumination. Without incubation prior to illumination
      2.1 +0.4 log was inactivated as determined by infectivity assay. When measured by
      PCR inhibition, inactivation varied inversely with amplicon size. When primers
      that spanned the entire coding region of the B19 genome were used, maximum
      inhibition of PCR amplification was demonstrated. CONCLUSION: Under defined
      conditions, PCT with amotosalen combined with UVA light can be used to inactivate
      B19, a clinically significant virus that can be transmitted through blood
      transfusion, and heretofore has been demonstrated to be refractory to
      inactivation.

PMID- 17524099
TI  - Planning for pandemic influenza: effect of a pandemic on the supply and demand
      for blood products in the United States.
AB  - BACKGROUND: Influenza causes episodic pandemics when viral antigens shift in ways
      that elude herd immunity. Avian influenza A H5N1, currently epizootic in bird
      populations in Asia and Europe, appears to have pandemic potential. STUDY DESIGN
      AND METHODS: The virology of influenza, the history of the 1918 pandemic, and the
      structure of the health care and the blood transfusion systems are briefly
      reviewed. Morbidity and mortality experience from the 1918 pandemic are projected
      onto the current health care structure to predict points of failure that are
      likely in a modern pandemic. RESULTS: Blood donor centers are likely to
      experience loss of donors, workers, and reliable transport of specimens to
      national testing laboratories and degradation of response times from national
      testing labs. Transfusion services are likely to experience critical losses of
      workers and of reagent red cells (RBCs) that will make their automated procedures
      unworkable. Loss of medical directors, supervisors, and lead technicians may make
      alternative procedures unworkable as well. CONCLUSIONS: Lower blood collection
      capacity and transfusion service support capability will reduce the availability
      of RBCs and especially of platelets. Plans for rationing medical care need to
      take the vulnerability of the blood transfusion system into account.

PMID- 17524100
TI  - Influenza viremia and the potential for blood-borne transmission.

PMID- 17524101
TI  - Transfusion premedications: a growing practice not based on evidence.

PMID- 17524103
TI  - Industry and medicine: conflicting interests and the power of money.

PMID- 17524104
TI  - Identification of platelet factor 4 and beta-thromboglobulin by profiling and
      liquid chromatography tandem mass spectrometry of supernatant peptides in stored
      apheresis and buffy-coat platelet concentrates.

PMID- 17524105
TI  - The National Marrow Donor Program with emphasis on the early years.

PMID- 17524106
TI  - Sequence analysis confirmation of transfusion-transmitted hepatitis C by red
      blood cells that tested negative by minipool hepatitis C virus nucleic acid
      testing.

PMID- 17524108
TI  - Acute myocardial infarction without disrupted yellow plaque in young patients
      below 50 years old.
AB  - OBJECTIVE: Thrombosis caused by disrupted yellow plaque is regarded as a cause of
      acute myocardial infarction (MI). However, it has not been clarified if young
      patients have the same pathophysiology as older ones. Therefore, we elucidated
      clinical and angioscopic characteristics of young patients. METHODS: Among a
      series of patients (n = 893) who received catheterization for acute MI, clinical
      characteristics were compared between patients <50 years (n = 66) and the rest of
      patients. Angioscopic appearance of culprit lesions was evaluated in 20 young
      patients in whom angioscopic examination was successfully performed. It was
      determined if culprit lesions had disrupted yellow plaque with thrombus (DYP&T).
      RESULTS: Patients <50 years had higher prevalence of smoking (68% vs. 48%, P =
      0.001), obesity (42% vs. 15%, P < 0.0001), and hypercholesterolemia (56% vs. 35%,
      P = 0.0005) than those >or=50 years. DYP&T was detected at culprit lesions in 14
      (70%) patients. Prevalence of DYP&T was lower in patients <40 years (44% vs. 91%,
      P = 0.02) than those between 40 and 50 years. Patients <40 years had a trend for
      higher prevalence of smoking (88% vs. 62%, P = 0.05) than those between 40 and 50
      years. CONCLUSIONS: Patients with acute MI < 50 years, especially <40 years, had
      lower prevalence of DYP&T but higher prevalence of smoking, obesity, and
      hypercholesterolemia. Smoking may play an important role for thrombotic occlusion
      at lesions with relatively low thrombogenic potential.

PMID- 17524109
TI  - Racial disparity in clinical outcomes following primary percutaneous coronary
      intervention for ST elevation myocardial infarction: influence of process of
      care.
AB  - Previous studies have shown that compared with white patients, non-white patients
      with ST elevation myocardial infarction (STEMI) have worse clinical outcomes.
      Differences in co-morbidities, extent and severity of coronary artery disease,
      health insurance, and socioeconomic status have been identified as possible
      reasons for this disparity. However, an alternative explanation for such observed
      disparities in outcomes could be differences in process of care. For example, in
      most of these studies, non-white patients were less likely to receive reperfusion
      therapy, and if treated, were more likely to receive thrombolysis than to undergo
      primary percutaneous coronary intervention (PCI). We hypothesized that if all
      patients were treated similarly with primary PCI, there would be no difference in
      clinical outcomes. We analyzed the demographic, angiographic, in-hospital
      clinical outcomes, and long-term mortality rates of a racially diverse group of
      patients presenting to the same hospital with STEMI, all of whom were treated
      with primary PCI. Our data demonstrate that compared with white patients, non
      white patients with STEMI who undergo primary PCI have similar in-hospital
      clinical outcomes and one-year mortality. This suggests that the previously
      observed differences in mortality rates may be, at least in part, attributable to
      differences in the process of care, and not solely to differences in patient
      factors or differential therapeutic effects.

PMID- 17524110
TI  - MRI evaluation of local myocardial treatments: epicardial versus endocardial
      (Cell-Fix catheter) injections.
AB  - AIMS: We compared two procedures for local myocardial treatment: transepicardial
      versus transendocardial catheter injection. Transepicardial injections were
      performed under direct surgical visualization whereas transendocardial injections
      were performed using electrophysiological guidance. METHODS: A left ventricle
      (LV) myocardial infarction (MI) was surgically created in 14 sheep. At 3 months,
      gadolinium was injected IV followed by the injection of super paramagnetic iron
      oxide (SPIO) into MI. Animals were divided in two groups: transepicardial
      injection (Group I) versus transendocardial (Group II) using "Cell-Fix" catheter
      injection. This catheter was developed to identify by electrophysiology the
      infarcted area and to stabilize injections suctioning the device to the
      endocardium. Postgadolinium delayed-enhancement magnetic resonance imaging (MRI)
      was performed to stain the infarct size. SPIO injections were used to assess the
      magnitude of the treated area. The ratio between SPIO black stained treatment
      areas and white gadolinium stained infarcted areas was calculated using MRI.
      RESULTS: The electrophysiological recordings by the catheter for the MI versus
      normal LV wall were: R wave amplitude 4.16 versus 12.08 mV (P = 0.003), slew rate
      (slope of the signal) 0.36 V/s versus 1.04 V/s (P = 0.008). The ratio of the SPIO
      diffusion into the MI was 41.2 +/- 8.1% for surgical and 63.7 +/- 8.2% for
      percutaneous endocardial injections (P = 0.0132). CONCLUSION: MRI allows
      evaluation of the extent of local myocardial treatments. The differences shown
      between epicardial and endocardial injections concerning the distribution of SPIO
      can be justified by the methodology of injection and by a more precise MI
      detection by electrophysiology. In conclusion, electrophysiological recordings to
      guide injections is superior to direct surgical visualization in terms of
      injecting into infarcted tissue.

PMID- 17524111
TI  - Temporal trends, safety, and efficacy of bivalirudin in elective percutaneous
      coronary intervention: insights from the Blue Cross Blue Shield of Michigan
      Cardiovascular Consortium.
AB  - OBJECTIVE: To evaluate the safety and efficacy of bivalirudin based therapy among
      patients undergoing percutaneous coronary intervention (PCI) for stable coronary
      artery disease in a large multicenter registry. BACKGROUND: The REPLACE I trial
      demonstrated the non-inferiority of a strategy of bivalirudin compared with
      heparin and glycoprotein (GP) IIbIIIa inhibition in patients undergoing PCI.
      There is a paucity of outcome data with bivalirudin use in the setting of real
      world PCI practice. METHODS: We evaluated the outcome of 11,719 patients who
      underwent elective PCI for stable coronary artery disease (CAD) from 2002 to 2004
      in a large regional consortium, and who were treated with bivalirudin (n = 2051)
      or with heparin and GP IIbIIIa inhibitors (n = 9,668). The primary endpoints were
      transfusion and in-hospital major adverse cardiovascular events (MACE) defined as
      the composite of death, MI, stroke, and any coronary artery bypass grafting
      (CABG) or target lesion revascularization. RESULTS: Compared with patients who
      received heparin plus GP IIbIIIa inhibitors, patients who received bivalirudin
      had a similar incidence of post-procedural MI, stroke, in-hospital death, MACE
      (2.88 vs. 2.48, P = 0.30), or transfusion (2.83% vs. 2.41%, P = 0.27). Patients
      at greater risk of bleeding were more likely to be treated with bivalirudin.
      After adjusting for the propensity to receive bivalirudin and for baseline co
      morbidities, there was no difference in the odds of MACE or the need for
      transfusion between the two groups. CONCLUSION: Compared with heparin plus GP
      IIbIIIa inhibition, use of bivalirudin in patients undergoing PCI for stable CAD
      is associated with similar ischemic and bleeding complications. Given the ease of
      administration and lower cost, bivalirudin provides an attractive treatment
      option in this patient population.

PMID- 17524112
TI  - Feasibility of percutaneous coronary interventions in early postcoronary artery
      bypass graft occlusion or stenosis.
AB  - BACKGROUND: With continuing technical advances in percutaneous coronary
      interventions (PCI) for coronary artery disease (CAD), patients undergoing
      coronary artery bypass surgery (CABG) often have complex coronary anatomy that is
      not ideal for PCI. Because of the complex anatomy, these patients have a higher
      risk of early graft occlusion. The feasibility of PCI in the treatment of early
      graft occlusion is not well established. METHODS: A retrospective chart review
      was performed of patients presenting with recurrent ischemia within three months
      post-CABG and at one-year follow-up. RESULTS: Forty-six patients with 156 grafts
      were identified. Three presented with STEMI, 21 with NSTEMI, 21 with unstable
      angina, and one with congestive heart failure. Sixty-three grafts were occluded
      or stenosed (>70%). Twenty-seven grafts (43%) in 17 patients were not amenable to
      PCI. The other 34 grafts (54%) in 23 patients underwent successful PCI. PCI was
      performed upon native vessels and occluded grafts with equal frequency. Six
      patients had patent grafts. At one-year follow-up, six of 23 patients in the PCI
      group were readmitted with ischemia; five vessels (14%) in four patients had
      restenosed. There were no deaths. In the group with no PCI, 11 of 23 patients
      were readmitted with ischemia with one death. CONCLUSION: PCI for early post-CABG
      occlusion was safely performed in slightly more than half of target vessels. PCI
      was performed upon native vessels and occluded grafts with equal frequency. After
      initial PCI success, the clinical target vessel restenosis rate was 14% at one
      year follow-up.

PMID- 17524113
TI  - Neutropenia in patients treated with thienopyridines and high-dose oral
      prednisone after percutaneous coronary interventions.
AB  - BACKGROUND: Oral treatment with prednisone has demonstrated efficacy in reducing
      restenosis after percutaneous coronary interventions (PCI). However,
      administration of steroids at high dose may raise concerns in terms of
      applicability and tolerability. Monitoring the occurrence of possible side
      effects is therefore mandatory. METHODS: Secondary effects of oral prednisone in
      this setting is analyzed. The "expected" secondary effects of the steroid
      treatment are described, together with the "unexpected" occurrence of likely drug
      induced neutropenia observed in patients prescribed prednisone and
      thienopyridines simultaneously after PCI. RESULTS: Two-hundred and twenty
      patients were monitored for the occurrence of side-effects of the prednisone
      therapy. Twenty-eight patients (14%) had side-effects likely related to the
      prednisone treatment: gastric pain (4%), increment of arterial pressure needing
      upgrading of antihypertensive treatment (4%), edema (1.8%), and concomitant
      infections (1.4%). In three patients (1.4%), agranulocytosis was detected at the
      time of the routine blood cell count scheduled 4 weeks after PCI in otherwise
      asymptomatic patients. Neutropenia subsided completely after withdrawal of
      prednisone and thienopyridine in all cases and the blood cell formula normalized
      within 3 weeks. CONCLUSIONS: Side-effects of oral prednisone given after PCI to
      reduce restenosis occur in less than 15% of patients. Complaints are mild and
      reversible and can be easily managed with adjunctive diuretic and antacid drugs.
      The occurrence of agranulocytosis after prednisone had never been reported
      before, but was observed in 1.4% of our patients receiving simultaneously a
      thienopyridine. To explain such an unusual event we propose the hypothesis of a
      possible metabolic interaction between prednisone and thienopyridines.

PMID- 17524114
TI  - Carotid artery stenting: a therapeutic alternative in subtotal internal carotid
      artery occlusions.
AB  - Carotid artery stenting (CAS) is emerging as a less invasive modality for
      treating atherosclerotic occlusive disease of the internal carotid artery (ICA).
      Randomized trials like the SAPPHIRE trial have demonstrated that CAS is not
      inferior to carotid endarterectomy (CEA) in the treatment of carotid artery
      stenosis, and maybe even superior in high-risk symptomatic patients. However,
      patients with subtotal ICA occlusions with thrombus are excluded from randomized
      CAS trials and CAS registries. To our knowledge, carotid angioplasty with
      stenting has not been attempted in these cases. We present three cases of
      symptomatic subtotal ICA occlusions successfully treated with CAS without any
      periprocedural complications. With careful patient selection and technical
      expertise, endovascular management could be considered as a treatment option in
      subtotal carotid occlusions.

PMID- 17524115
TI  - Contemporary percutaneous treatment of infrapopliteal arterial disease: a
      practical approach.

PMID- 17524116
TI  - Pathology may help decision making in asymptomatic carotid disease.

PMID- 17524117
TI  - Contrast-induced nephropathy remains a serious complication of PCI.

PMID- 17524119
TI  - Cultivation gives context to the microbial ecologist.

PMID- 17524120
TI  - The plate debate: cultivable communities have no utility in contemporary
      environmental microbial ecology.

PMID- 17524121
TI  - What is anti-aging?

PMID- 17524122
TI  - Skin hydration: a review on its molecular mechanisms.
AB  - Water is absolutely essential for the normal functioning of the skin and
      especially its outer layer, the stratum corneum (SC). Loss of water from the skin
      must be carefully regulated, a function dependent on the complex nature of the
      SC. The retention of water in the SC is dependent on two major components: (1)
      the presence of natural hygroscopic agents within the corneocytes (collectively
      referred to as natural moisturizing factor) and (2) the SC intercellular lipids
      orderly arranged to form a barrier to transepidermal water loss (TEWL). The water
      content of the SC is necessary for proper SC maturation and skin desquamation.
      Increased TEWL impairs enzymatic functions required for normal desquamation
      resulting in the visible appearance of dry, flaky skin. There have been recent
      discoveries regarding the complex mechanisms of skin hydration. In particular, it
      has been discovered that glycerol, a well-known cosmetic ingredient, exists in
      the SC as a natural endogenous humectant. Hyaluronan, which has been regarded
      mainly as dermal component, is found in the epidermis and is important for
      maintaining normal SC structure and epidermal barrier function. More importantly,
      the discovery of the existence of the water-transporting protein aquaporin-3 in
      the viable epidermis and the presence of tight junction structures at the
      junction between the stratum granulosum and SC have brought new insights into the
      mechanisms of skin water distribution and barrier function.

PMID- 17524123
TI  - A hydroquinone formulation with increased stability and decreased potential for
      irritation.
AB  - BACKGROUND: Long-term treatment with a high-strength hydroquinone (HQ) cream
      (usually 4% HQ) is the mainstay therapy for hyperpigmentation disorders.
      Instability and high potential for irritancy hinders patient compliance. A new 4%
      HQ preparation has been designed with an innovative antioxidant for stability and
      a biomimetic of an herbal extract for skin calming. AIMS: To investigate the
      activity, stability, and irritancy of a new HQ cream. METHODS: To evaluate the
      new HQ cream in comparison with commercial 4% HQ creams for stability by
      temperature stress test, for irritancy by repeated-insult patch test on human
      subjects, and for lightening effect using the MelanoDerm B skin equivalent model.
      RESULTS: The new HQ is more resistant to browning and shows less irritancy than
      three commercially available 4% HQ products. It has comparable bleaching effect
      with faster onset than a 4% HQ product containing 0.05% tretinoin and 0.01%
      fluocinolone acetonide. CONCLUSION: Based on its improved stability, lower
      irritancy, and activity in skin lightening, the new approach to the formulation
      of 4% HQ may improve therapeutic outcomes by improving patient compliance to
      dosing.

PMID- 17524124
TI  - Combined trichloroacetic acid peel and topical ascorbic acid versus
      trichloroacetic acid peel alone in the treatment of melasma: a comparative study.
AB  - BACKGROUND: Melasma is a common acquired hypermelanosis that is difficult to
      treat. Several chemical peeling agents were used in treatment of melasma. Topical
      vitamin C was also used with minimal side effects. AIM: To compare the effect of
      20% trichloroacetic acid (TCA) peel alone vs. 20% TCA peel combined with topical
      5% ascorbic acid in cases of epidermal melasma. PATIENTS AND METHODS: Thirty
      women with bilateral epidermal melasma (Fitzpatrick skin types III and IV) were
      divided into two groups (A and B, 15 patients each). Before therapy, digital
      photography and a melasma area and severity index (MASI) score were done for each
      patient. Groups A and B were primed for 2 weeks before TCA peel. Group B also
      applied 5% ascorbic acid topically once daily; 20% TCA peel was done for all
      patients weekly until clearance of melasma or for a maximum of six peels. Group B
      continued to use 5% ascorbic acid topically in between peels and during the 16
      week follow-up period. Patients were assessed at the end of peeling sessions and
      at the end of follow-up by photography, MASI score, and a global evaluation by
      the patient. RESULTS: Group B compared with group A showed a significant decrease
      in MASI score at the end of TCA peels (P < 0.001) and at the end of the 16-week
      follow-up period (P < 0.003). Global evaluation showed that 13 patients (87%) in
      group B improved or maintained their improvement compared with only 10 patients
      (67%) in group A. CONCLUSION: Topical ascorbic acid combined with 20% TCA peel in
      melasma improves the results and helps in maintaining the response to therapy.

PMID- 17524125
TI  - Adverse reactions to polylactic acid injections in the periorbital area.
AB  - BACKGROUND: Correction of aging changes and contour deformities has been
      addressed largely by tissue augmentation agents whose volume is injected into
      tissues to achieve the required result. Polylactic acid (PLA) is an agent that is
      injected with the aim of enhancing the host's own collagen deposition. OBJECTIVE:
      We describe the development of multiple nodules and one case of a foreign-body
      granuloma formation following the administration of PLA to the face for
      correction of rhytides and contour deformities. Methods Four case presentations,
      including clinical history, injection protocol, histopathology, individual
      treatment, and their outcomes, are discussed with pertinent literature review.
      RESULTS: Four patients who received injections of PLA developed nodules that were
      clinically similar in size, shape, and consistency. Histopathologic examination
      revealed the presence of a foreign-body granulomatous inflammatory reaction in
      one of the patients. CONCLUSION: Cosmetic treatment with PLA may be complicated
      by disfiguring nodules that may mask a granulomatous reaction. PLA-induced
      nodules and foreign-body granulomas have proven difficult to treat. Therefore,
      PLA should only be injected in the infraorbital area by experienced injectors who
      have had appropriate training. In addition to this, PLA should be injected in a
      "depot" method below the muscle at a significantly diluted volume. Due to the
      complications encountered after the use of PLA, we feel that a cautionary warning
      regarding the use of PLA in this area may be prudent regardless of the
      abovementioned precautions.

PMID- 17524126
TI  - Evaluation of the effects of caffeine in the microcirculation and edema on thighs
      and buttocks using the orthogonal polarization spectral imaging and clinical
      parameters.
AB  - Gynoid lipodystrophy, also known as cellulite, is a common multifactorial entity
      that affects millions of women around the world. There have been few scientific
      articles dealing with its physiology and treatment in the past few years, and
      vascular changes seem to play an important role in its pathophysiology. Skin
      microvascular alterations can be observed noninvasively with a new method called
      orthogonal polarization spectral imaging, which was used to evaluate the
      effectiveness of an anticellulite drug composed mainly of a 7% caffeine solution.
      Microcirculatory parameters evaluated were functional capillary density (FCD;
      number of flowing capillaries per unit area), diameter of the dermic papilla
      (DPD), and capillary diameter (CD). The clinical parameters analyzed were
      centimetrical measurements of thighs and hips and the influence of tobacco,
      alcohol, and physical activities on the efficacy of the treatment. After 1 month
      of treatment, statistical application of chi-squared and Z approximation tests
      showed, in treated patients, statistically significant reduction of thigh
      circumferences in more than 80% of the cases and reduction of hip circumference
      in 67.7%. FCD, DPD, and CD did not change significantly after treatment. Smoking
      as well as alcohol consumption and regular physical activity were not
      significantly related to the centimetrical reduction observed in treated thighs
      and hips.

PMID- 17524127
TI  - Development and evaluation of polyherbal formulation for hair growth-promoting
      activity.
AB  - BACKGROUND: Cuscuta reflexa (Roxb.), Citrullus colocynthis (Schrad.), and Eclipta
      alba (Hassk.) are traditionally acclaimed herbs for their hair growth-promoting
      potential. Aim In the present study, it was envisaged to prepare herbal
      formulations containing petroleum ether extracts of the three herbs in varying
      ratio and evaluating the formulations for the hair growth-promoting activity.
      METHODS: The formulations as well as minoxidil (2%) solution (positive control)
      were applied topically on shaved skin of rats, and the time required for
      initiation and completion of hair growth cycle was recorded. RESULTS AND
      CONCLUSIONS: Hair growth initiation time was markedly reduced to one third on
      treatment with the prepared formulation compared with control animals. The time
      required for complete hair growth was also reduced by 32%. Quantitative analysis
      of hair growth cycle after treatment with formulations and minoxidil (2%)
      exhibited greater number of hair follicles in anagenic phase compared with
      control. The results thus corroborate with the traditionally acclaimed hair
      growth-promoting capabilities of the plants. The prepared formulation also holds
      potential for treatment of alopecia.

PMID- 17524128
TI  - Clinical and instrumental study of the efficacy of a new sebum control cream.
AB  - BACKGROUND: Some botanical compounds are considered useful to reduce sebum
      production. Aim To evaluate the efficacy of a sebum control cream containing
      polyphenol-rich extract from saw palmetto, sesame seeds, and argan oil in
      subjects with oily facial skin. METHODS: The study was carried out during the
      winter months (January and February). A total of 20 healthy volunteers (9 male
      and 11 female, aged 17-50 years, 16 with oily skin and 4 with combined skin) were
      studied. The test product was applied twice daily to the face for a period of 4
      weeks. A clinical assessment and instrumental measurements were done before and
      after the treatment period. Casual sebum level on the forehead and both cheeks
      was determined with a photometric device (Sebumeter). The quantity of sebum on
      the midforehead was determined using sebum collector foils (Sebufix), which were
      then evaluated with skin camera Visioscope and software SELS (Surface Evaluation
      of the Living Skin). A subjective evaluation questionnaire regarding the cosmetic
      characteristics, tolerance, and efficacy of the product was filled out by the
      volunteers at the end of study. RESULTS: The product was very well accepted by
      all the volunteers. A visible sebum-regulating efficacy was reported in 95% of
      them. After 4 weeks of treatment, the clinical assessment scores decreased by
      33%. There was a significant reduction in the casual sebum level by 20% and area
      covered with oily spots by 42%. The number of active sebaceous glands remained
      unaltered. CONCLUSION: These results objectively and quantitatively show the
      efficacy of the sebum control cream tested to reduce the greasiness and improve
      the appearance of oily facial skin.

PMID- 17524129
TI  - Epithelial grafting for vitiligo requires ultraviolet A phototherapy to increase
      success rate.
AB  - BACKGROUND: Phototherapeutic techniques were introduced into medical practice by
      the ancient Egyptians. It is considered a cornerstone in the management of
      resistant vitiligo; yet, failures are very well known. Recently, the introduction
      of surgical techniques provided a major development in the management of vitiligo
      and replaced other conventional unsuccessful therapies. OBJECTIVES: The aim of
      this work is to find out if phototherapy, which failed to resolve the vitiligo
      problem in patients, is still required in the treatment strategy after epithelial
      grafting of the same cases. METHODS: Twenty-five vitiligo patients, nonresponding
      to classic phototherapy, were treated surgically. Ultrathin Thiersch grafts and
      suction blister grafts were used. Phototherapy using ultraviolet A (UVA) bulbs in
      combination with psoralen or khellin was used postoperatively immediately after
      take of grafts onto recipient sites. RESULTS: In spite of reactivation of
      depigmentary effects at grafted areas, phototherapy acted as a stimulator for
      melanocytic proliferation and function and as an immunosuppressant, halting the
      melanocytic destructive process. The application of UVA phototherapy resulted in
      successful treatment in the patients receiving it. CONCLUSION: The success of
      epithelial grafting in patients with vitiligo can be increased by UVA
      phototherapy.

PMID- 17524130
TI  - Vth World Congress of the International Academy of Cosmetic Dermatology,
      Melbourne, Australia, December 9-13, 2006.

PMID- 17524131
TI  - Transcriptional effect of an Aframomum angustifolium seed extract on human
      cutaneous cells using low-density DNA chips.
AB  - BACKGROUND: Studying photoexposed and photoprotected skin biopsies from young and
      aged women, it has been found that a specific zone, composed of the basal layers
      of the epidermis, the dermal epidermal junction, and the superficial dermis, is
      major target of aging and reactive oxygen species. We showed that this zone is
      characterized by significant variations at a transcriptional and/or protein
      levels. AIMS: Using low-density DNA chip technology, we evaluated the effect of a
      natural mixture of Aframomum angustifolium seed extract containing labdane
      diterpenoids on these aging markers. METHODS: Expression profiles of normal human
      fibroblasts (NHF) were studied using a customized cDNA macroarray system
      containing genes covering dermal structure, inflammatory responses, and oxidative
      stress defense mechanisms. For normal human keratinocyte (NHK) investigations, we
      chose OLISA technique, a sensitive and quantitative method developed by
      BioMerieux specifically designed to investigate cell death, proliferation,
      epidermal structure, differentiation, and oxidative stress defense response.
      RESULTS: We observed that this extract strongly modified gene expression profiles
      of treated NHK, but weakly for NHF. This extract regulated antioxidant defenses,
      dermal-epidermal junction components, and epidermal renewal-related genes.
      CONCLUSION: Using low-density DNA chip technology, we identified new potential
      actions of A. angustifolium seed extract on skin aging.

PMID- 17524132
TI  - The pathogenesis of cellulite: a new concept.

PMID- 17524133
TI  - Predicting a low cortisol response to adrenocorticotrophic hormone in the
      critically ill: a retrospective cohort study.
AB  - INTRODUCTION: Identification of risk factors for diminished cortisol response to
      adrenocorticotrophic hormone (ACTH) in the critically ill could facilitate
      recognition of relative adrenal insufficiency in these patients. Therefore, we
      studied predictors of a low cortisol response to ACTH. METHODS: A retrospective
      cohort study was conducted in a general intensive care unit of a university
      hospital over a three year period. The study included 405 critically ill
      patients, who underwent a 250 microg ACTH stimulation test because of prolonged
      hypotension or need for vasopressor/inotropic therapy. Plasma cortisol was
      measured before and 30 and 60 min after ACTH injection. A low adrenal response
      was defined as an increase in cortisol of less than 250 nmol/l or a peak cortisol
      level below 500 nmol/l. Various clinical variables were collected at admission
      and on the test day. RESULTS: A low ACTH response occurred in 63% of patients.
      Predictors, in multivariate analysis, included sepsis at admission, low
      platelets, low pH and bicarbonate, low albumin levels, high Sequential Organ
      Failure Assessment score and absence of prior cardiac surgery, and these
      predictors were independent of baseline cortisol and intubation with etomidate.
      Baseline cortisol/albumin ratios, as an index of free cortisol, were directly
      related and increases in cortisol/albumin were inversely related to disease
      severity indicators such as the Simplified Acute Physiology Score II and
      Sequential Organ Failure Assessment score (Spearman r = -0.21; P < 0.0001).
      CONCLUSION: In critically ill patients, low pH/bicarbonate and platelet count,
      greater severity of disease and organ failure are predictors of a low
      adrenocortical response to ACTH, independent of baseline cortisol values and
      cortisol binding capacity in blood. These findings may help to delineate relative
      adrenal insufficiency and suggest that adrenocortical suppression occurs as a
      result of metabolic acidosis and coagulation disturbances.

PMID- 17524134
TI  - Identification of candidate regulatory sequences in mammalian 3' UTRs by
      statistical analysis of oligonucleotide distributions.
AB  - BACKGROUND: 3' untranslated regions (3' UTRs) contain binding sites for many
      regulatory elements, and in particular for microRNAs (miRNAs). The importance of
      miRNA-mediated post-transcriptional regulation has become increasingly clear in
      the last few years. RESULTS: We propose two complementary approaches to the
      statistical analysis of oligonucleotide frequencies in mammalian 3' UTRs aimed at
      the identification of candidate binding sites for regulatory elements. The first
      method is based on the identification of sets of genes characterized by
      evolutionarily conserved overrepresentation of an oligonucleotide. The second
      method is based on the identification of oligonucleotides showing statistically
      significant strand asymmetry in their distribution in 3' UTRs. CONCLUSION: Both
      methods are able to identify many previously known binding sites located in
      3'UTRs, and in particular seed regions of known miRNAs. Many new candidates are
      proposed for experimental verification.

PMID- 17524135
TI  - A novel nested multiplex polymerase chain reaction (PCR) assay for differential
      detection of Entamoeba histolytica, E. moshkovskii and E. dispar DNA in stool
      samples.
AB  - BACKGROUND: E. histolytica, a pathogenic amoeba, is indistinguishable in its cyst
      and trophozoite stages from those of non-pathogenic E. moshkovskii and E. dispar
      by light microscopy. We have developed a nested multiplex PCR targeting a 16S
      like rRNA gene for differential detection of all the three morphologically
      similar forms of E. histolytica, E. moshkovskii and E. dispar simultaneously in
      stool samples. RESULTS: The species specific product size for E. histolytica, E.
      moshkovskii and E. dispar was 439, 553 and 174 bp respectively, which was clearly
      different for all the three Entamoeba species. The nested multiplex PCR showed a
      sensitivity of 94% and specificity of 100% for the demonstration of E.
      histolytica, E. moshkovskii and E. dispar DNA in stool samples. The PCR was
      positive for E. histolytica, E. moshkovskii and E. dispar in a total of 190 out
      of 202 stool specimens (94% sensitive) that were positive for E. histolytica/E.
      dispar/E. moshkovskii by examination of stool by microscopy and/or culture. All
      the 35 negative control stool samples that were negative for E. histolytica/E.
      dispar/E. moshkovskii by microscopy and culture were also found negative by the
      nested multiplex PCR (100% specific). The result from the study shows that only
      34.6% of the patient stool samples that were positive for E. histolytica/E.
      dispar/E. moshkovskii by examination of stool by microscopy and/or culture, were
      actually positive for pathogenic E. histolytica and the remaining majority of the
      stool samples were positive for non-pathogenic E. dispar or E. moshkovskii as
      demonstrated by the use of nested multiplex PCR. CONCLUSION: The present study
      reports a new nested multiplex PCR strategy for species specific detection and
      differentiation of E. histolytica, E. dispar and E. moshkovskii DNA in stool
      specimens. The test is highly specific, sensitive and also rapid, providing the
      results within 12 hours of receiving stool specimens.

PMID- 17524136
TI  - RMBNToolbox: random models for biochemical networks.
AB  - BACKGROUND: There is an increasing interest to model biochemical and cell
      biological networks, as well as to the computational analysis of these models.
      The development of analysis methodologies and related software is rapid in the
      field. However, the number of available models is still relatively small and the
      model sizes remain limited. The lack of kinetic information is usually the
      limiting factor for the construction of detailed simulation models. RESULTS: We
      present a computational toolbox for generating random biochemical network models
      which mimic real biochemical networks. The toolbox is called Random Models for
      Biochemical Networks. The toolbox works in the Matlab environment, and it makes
      it possible to generate various network structures, stoichiometries, kinetic laws
      for reactions, and parameters therein. The generation can be based on statistical
      rules and distributions, and more detailed information of real biochemical
      networks can be used in situations where it is known. The toolbox can be easily
      extended. The resulting network models can be exported in the format of Systems
      Biology Markup Language. CONCLUSION: While more information is accumulating on
      biochemical networks, random networks can be used as an intermediate step towards
      their better understanding. Random networks make it possible to study the effects
      of various network characteristics to the overall behavior of the network.
      Moreover, the construction of artificial network models provides the ground truth
      data needed in the validation of various computational methods in the fields of
      parameter estimation and data analysis.

PMID- 17524138
TI  - Ethics takes time, but not that long.
AB  - BACKGROUND: Time and communication are important aspects of the medical
      consultation. Physician behavior in real-life pediatric consultations in relation
      to ethical practice, such as informed consent (provision of information,
      understanding), respect for integrity and patient autonomy (decision-making), has
      not been subjected to thorough empirical investigation. Such investigations are
      important tools in developing sound ethical praxis. METHODS: 21 consultations for
      inguinal hernia were video recorded and observers independently assessed global
      impressions of provision of information, understanding, respect for integrity,
      and participation in decision making. The consultations were analyzed for the
      occurrence of specific physician verbal and nonverbal behaviors and length of
      time in minutes. RESULTS: All of the consultations took less than 20 minutes, the
      majority consisting of 10 minutes or less. Despite this narrow time frame, we
      found strong and consistent association between increasing time and higher
      ratings on all components of ethical practice: information, (beta = .43),
      understanding (beta = .52), respect for integrity (beta = .60), and decision
      making (beta = .43). Positive nonverbal behaviors by physicians during the
      consultation were associated particularly with respect for integrity (beta =.36).
      Positive behaviors by physicians during the physical examination were related to
      respect for children's integrity. CONCLUSION: Time was of essence for the ethical
      encounter. Further, verbal and nonverbal positive behaviors by the physicians
      also contributed to higher ratings of ethical aspects. These results can help to
      improve quality of ethical practice in pediatric settings and are of relevance
      for teaching and policy makers.

PMID- 17524137
TI  - A review of the methodological features of systematic reviews in maternal
      medicine.
AB  - BACKGROUND: In maternal medicine, research evidence is scattered making it
      difficult to access information for clinical decision making. Systematic reviews
      of good methodological quality are essential to provide valid inferences and to
      produce usable evidence summaries to guide management. This review assesses the
      methodological features of existing systematic reviews in maternal medicine,
      comparing Cochrane and non-Cochrane reviews in maternal medicine. METHODS:
      Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane
      Database of Systematic Reviews (CDSR) were searched for relevant reviews
      published between 2001 and 2006. We selected those reviews in which a minimum of
      two databases were searched and the primary outcome was related to the maternal
      condition. The selected reviews were assessed for information on framing of
      question, literature search and methods of review. RESULTS: Out of 2846
      citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews.
      Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall,
      54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a
      detailed search description, only 17/68 (25%) searched without language
      restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%)
      assessed for the risk of missing studies quantitatively. The reviews had
      deficiencies in the assessment of validity of studies and exploration for
      heterogeneity. When compared to Cochrane reviews, other reviews were
      significantly inferior in specifying questions (OR 20.3, 95% CI 1.1-381.3, p =
      0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of
      unpublished data (OR 5.6, 95% CI 1.9-16.4, p = 0.002), assessment for
      heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR
      3.7, 95% CI 1.3-10.8, p = 0.02). CONCLUSION: This study identifies areas which
      have a strong influence on maternal morbidity and mortality but lack good quality
      systematic reviews. Overall quality of the existing systematic reviews was
      variable. Cochrane reviews were of better quality as compared to other reviews.
      There is a need for good quality systematic reviews to inform practice in
      maternal medicine.

PMID- 17524139
TI  - Expression of CD80 and CD86 costimulatory molecules are potential markers for
      better survival in nasopharyngeal carcinoma.
AB  - BACKGROUND: B7 Costimulatory signal is essential to trigger T-cell activation
      upon the recognition of tumor antigens. This study examined the expression of B7
      1 (CD80) and B7-2 (CD86) costimulatory molecules along with HLA-DR and the
      presence of infiltrating lymphocytes and dendritic cells to assess their
      significance in patients with nasopharyngeal carcinoma (NPC). METHODS: Expression
      of CD80, CD86, HLA-DR, S-100 protein and the presence of infiltrating lymphocytes
      and follicular dendritic reticulum cells were immunohistochemically examined on
      the paraffin-embedded tissue blocks from newly diagnosed NPC patients (n = 50).
      The results were correlated with clinical outcome of patients. RESULTS: CD80 and
      CD86 were each expressed in 10 of 50 cases in which they co-expressed in 9 cases.
      Univariate analysis revealed that patients with CD80/CD86 expression had
      significantly better overall survival than those without it (P = 0.017), but
      after adjustment for stage, nodal status, and treatment, the expression of
      CD80/CD86 did not significantly correlate with overall survival. Expression of
      HLA-DR and the presence of infiltrating lymphocytes and dendritic cells did not
      appear to have impact on the survival of patients. CONCLUSION: Expression of CD80
      and CD86 costimulatory molecules appears to be a marker of better survival in
      patient with NPC.

PMID- 17524140
TI  - Diverse histone modifications on histone 3 lysine 9 and their relation to DNA
      methylation in specifying gene silencing.
AB  - BACKGROUND: Previous studies of individual genes have shown that in a self
      enforcing way, dimethylation at histone 3 lysine 9 (dimethyl-H3K9) and DNA
      methylation cooperate to maintain a repressive mode of inactive genes. Less clear
      is whether this cooperation is generalized in mammalian genomes, such as mouse
      genome. Here we use epigenomic tools to simultaneously interrogate chromatin
      modifications and DNA methylation in a mouse leukemia cell line, L1210. RESULTS:
      Histone modifications on H3K9 and DNA methylation in L1210 were profiled by both
      global CpG island array and custom mouse promoter array analysis. We used
      chromatin immunoprecipitation microarray (ChIP-chip) to examine acetyl-H3K9 and
      dimethyl-H3K9. We found that the relative level of acetyl-H3K9 at different
      chromatin positions has a wider range of distribution than that of dimethyl-H3K9.
      We then used differential methylation hybridization (DMH) and the restriction
      landmark genome scanning (RLGS) to analyze the DNA methylation status of the same
      targets investigated by ChIP-chip. The results of epigenomic profiling, which
      have been independently confirmed for individual loci, show an inverse
      relationship between DNA methylation and histone acetylation in regulating gene
      silencing. In contrast to the previous notion, dimethyl-H3K9 seems to be less
      distinct in specifying silencing for the genes tested. CONCLUSION: This study
      demonstrates in L1210 leukemia cells a diverse relationship between histone
      modifications and DNA methylation in the maintenance of gene silencing. Acetyl
      H3K9 shows an inverse relationship between DNA methylation and histone
      acetylation in regulating gene silencing as expected. However, dimethyl-H3K9
      seems to be less distinct in relation to promoter methylation. Meanwhile, a
      combination of epigenomic tools is of help in understanding the heterogeneity of
      epigenetic regulation, which may further our vision accumulated from single-gene
      studies.

PMID- 17524141
TI  - CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia
      reperfusion injury in P-selectin/ICAM-1 deficient mice.
AB  - BACKGROUND: Neutrophil adhesion and migration are critical in hepatic ischemia
      and reperfusion injury (I/R). P-selectin and the intercellular adhesion molecule
      (ICAM)-1 can mediate neutrophil-endothelial cell interactions, neutrophil
      migration, and the interactions of neutrophils with hepatocytes in the liver.
      Despite very strong preclinical data, recent clinical trials failed to show a
      protective effect of anti-adhesion therapy in reperfusion injury, indicating that
      the length of injury might be a critical factor in neutrophil infiltration.
      Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1
      in neutrophil infiltration and liver injury during early and late phases of liver
      I/R. METHODS: Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null)
      mice underwent 90 minutes of partial liver ischemia followed by various periods
      of reperfusion (6, 15 h, and a survival study). Liver injury was assessed by
      plasma level of alanine aminotransferase (ALT) and histopathology. The plasma
      cytokines, TNF-alpha, IL-6, MIP-2 and KC, were measured by ELISA. RESULTS:
      Reperfusion caused significant hepatocellular injury in both wild-type and P/I
      null mice as was determined by plasma ALT levels and liver histopathology. The
      injury was associated with a marked neutrophil infiltration into the ischemic
      livers of both wild-type and P/I null mice. Although the levels of ALT and
      neutrophil infiltration were slightly lower in the P/I null mice compared with
      the wild-type mice the differences were not statistically significant. The plasma
      cytokine data of TNF-alpha and IL-6 followed a similar pattern to ALT data, and
      no significant difference was found between the wild-type and P/I null groups. In
      contrast, a significant difference in KC and MIP-2 chemokine levels was observed
      between the wild-type and P/I null mice. Additionally, the survival study showed
      a trend towards increased survival in the P/I null group. CONCLUSION: While ICAM
      1 and P-selectin does not appear to be critical for neutrophil infiltration and
      I/R injury in the liver, they may regulate CXC-chemokine production. Blockage of
      these adhesion molecules may improve survival and remote organ injury that often
      accompanies liver I/R injury, through chemokine regulation.

PMID- 17524142
TI  - Concomitant mitral valve surgery with aortic valve replacement: a 21-year
      experience with a single mechanical prosthesis.
AB  - BACKGROUND: Long-term survival for combined aortic and mitral valve replacement
      appears to be determined by the mitral valve prosthesis from our previous
      studies. This 21-year retrospective study assess long-term outcome and durability
      of aortic valve replacement (AVR) with either concomitant mitral valve
      replacement (MVR) or mitral valve repair (MVrep). We consider only a single
      mechanical prosthesis. METHODS: Three hundred and sixteen patients underwent
      double valve replacement (DVR) (n = 273) or AVR+MVrep (n = 43), in the period
      1977 to 1997. Follow up of 100% was achieved via telephone questionnaire and
      review of patients' medical records. Actuarial analysis of long-term survival was
      determined by Kaplan-Meier method. The Cox regression model was used to evaluate
      potential predictors of mortality. RESULTS: There were seventeen cases (5.4%) of
      early mortality and ninety-six cases of late mortality. Fifteen-year survival was
      similar in both groups at 44% and 57% for DVR and AVR+MVrep respectively. There
      were no significant differences in valve related deaths, anticoagulation related
      complications, or prosthetic valve endocarditis between the groups. There were 6
      cases of periprosthetic leak in the DVR group. Sex, pre-operative mitral and
      aortic valve pathology or previous cardiac surgery did not significantly affect
      outcome. CONCLUSION: The mitral valve appears to be the determinant of survival
      following double valve surgery and survival is not significantly influenced by
      mitral valve repair.

PMID- 17524144
TI  - Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA
      polymerase.
AB  - BACKGROUND: Putative high mutation rates of RNA viruses are believed to mediate
      undesirable phenomena, such as emergence of drug resistance. However, very little
      is known about biochemical fidelity rates for viral RNA-dependent RNA
      polymerases. Using a recently developed in vitro polymerase assay for poliovirus
      polymerase 3Dpol [Arnold and Cameron (2000) JBC 275:5329], we measured fidelity
      for each possible mismatch. Polymerase fidelity, in contrast to sequence error
      rate, is biochemically defined as kpol/Kd of {(correct plus incorrect) divided by
      incorrect} incorporations, such that a larger value connotes higher fidelity.
      RESULTS: To derive kpol/Kd for correct base incorporation, we performed
      conventional pre-steady state single turnover measurements, yielding values that
      range from 0.62 to 9.4 microM-1 sec-1. Pre-steady state measurements for
      incorrect base incorporation were less straightforward: several anomalous
      phenomena interfered with data collection. To obtain pre-steady state kinetic
      data for incorrect base incorporation, three strategies were employed. (1) For
      some incorrect bases, a conventional approach was feasible, although care was
      taken to ensure that only single turnovers were being assessed. (2) Heparin or
      unlabeled RNA traps were used to simulate single turnover conditions. (3)
      Finally, for some incorrect bases, incorporation was so poor that single
      datapoints were used to provide kinetic estimates. Overall, we found that
      fidelity for poliovirus polymerase 3Dpol ranges from 1.2 x 10(4) to 1.0 x 10(6)
      for transition mutations and 3.2 x 10(5) to 4.3 x 10(7) for transversion
      mutations. CONCLUSION: These values are unexpectedly high showing that high RNA
      virus sequence variation is not due to intrinsically low polymerase fidelity.
      Based on unusual enzyme behavior that we observed, we speculate that RNA
      mismatches either directly or indirectly cause enzyme RNA dissociation. If so,
      high sequence variation of RNA viruses may be due to template-switch RNA
      recombination and/or unknown fitness/selection phenomena. These findings may lead
      to a mechanistic understanding of RNA virus error catastrophe and improved anti
      viral strategies.

PMID- 17524145
TI  - Global repeat discovery and estimation of genomic copy number in a large, complex
      genome using a high-throughput 454 sequence survey.
AB  - BACKGROUND: Extensive computational and database tools are available to mine
      genomic and genetic databases for model organisms, but little genomic data is
      available for many species of ecological or agricultural significance, especially
      those with large genomes. Genome surveys using conventional sequencing techniques
      are powerful, particularly for detecting sequences present in many copies per
      genome. However these methods are time-consuming and have potential drawbacks.
      High throughput 454 sequencing provides an alternative method by which much
      information can be gained quickly and cheaply from high-coverage surveys of
      genomic DNA. RESULTS: We sequenced 78 million base-pairs of randomly sheared
      soybean DNA which passed our quality criteria. Computational analysis of the
      survey sequences provided global information on the abundant repetitive sequences
      in soybean. The sequence was used to determine the copy number across regions of
      large genomic clones or contigs and discover higher-order structures within
      satellite repeats. We have created an annotated, online database of sequences
      present in multiple copies in the soybean genome. The low bias of pyrosequencing
      against repeat sequences is demonstrated by the overall composition of the survey
      data, which matches well with past estimates of repetitive DNA content obtained
      by DNA re-association kinetics (Cot analysis). CONCLUSION: This approach provides
      a potential aid to conventional or shotgun genome assembly, by allowing rapid
      assessment of copy number in any clone or clone-end sequence. In addition, we
      show that partial sequencing can provide access to partial protein-coding
      sequences.

PMID- 17524146
TI  - Expression of inflammatory host genes in Chlamydia trachomatis-infected human
      monocytes.
AB  - The aim of this study was to perform a comprehensive gene expression analysis of
      cytokines, chemokines, and their receptors in Chlamydia trachomatis-infected
      human monocytes in order to elucidate molecular aspects of their involvement in
      the host response. Peripheral blood mononuclear cells from three healthy donors
      were separated and infected with C. trachomatis elementary bodies serovar K
      (UW/31/Cx) at a multiplicity of infection of 5:1. Three time points of infection
      were studied by gene expression analysis using microarray: 4 hours (active
      infection), 1 day (transition), and 7 days (persistent infection). Expression
      levels of selected genes were confirmed by quantitative real-time reverse
      transcription-polymerase chain reaction. Transcripts encoding 10 cytokines,
      chemokines, and receptors were found to be upregulated exclusively in the early,
      active phase of the infection as compared to four genes in the late, persistent
      state of the infection. Apart from receptors, both the level and the number of
      transcripts encoding inflammatory products decreased with ongoing infection. Four
      genes (interferon-gamma, macrophage inflammatory protein [MIP]-1-alpha, MIP-1
      beta, and interleukin-2 receptor-gamma) were constantly expressed over a period
      of 7 days. The current study provides data on the induction of mRNA encoding
      cytokines, chemokines, and their receptors in C. trachomatis-infected human
      monocytes. This pro-inflammatory gene expression profile of the monocytic host
      cell showed several differences between active and persistent chlamydial
      infections.

PMID- 17524147
TI  - TRIPS, the Doha declaration and paragraph 6 decision: what are the remaining
      steps for protecting access to medicines?
AB  - BACKGROUND: The World Trade Organisation's Declaration on the TRIPS Agreement and
      Public Health (known as the Doha Declaration) of 2001, and subsequent Decision on
      the Interpretation of Paragraph 6 reached in 2003, affirmed the flexibilities
      available under the Agreement on Trade Related Property Rights (TRIPS) to member
      states seeking to protect public health. Despite these important clarifications,
      the actual implementation of these measures to improve access to medicines
      remains uncertain. There are also concerns that so-called TRIPS-plus measures
      within many regional and bilateral trade agreements are further undermining the
      capacity of the poor to access affordable medicines. METHODS: The paper reviews
      policy debates among governments, nongovernmental organisations and international
      organisations from 1995, and notably since 2003, surrounding access to medicines
      and trade agreements. The provisions for protecting public health provided by the
      Doha Declaration and Paragraph 6 Decision are reviewed in terms of challenges for
      implementation, along with measures to protect intellectual property rights
      (IPRs) under selected regional and bilateral trade agreements. RESULTS: While
      provisions, in principle, were affirmed for member states under the TRIPS
      agreement to protect public health, numerous challenges remain. Implementation of
      the flexibilities has been hindered by lack of capacity in many LMICs. More
      intransigent have been stark inequalities in power and influence among trading
      nations, leaving LMICs vulnerable to pressures to permit the globalization of
      IPRs in order to protect broader trade and economic interests. Such inequalities
      are apparent in proposals or adopted TRIPS-plus measures which re-establish the
      primacy of trade over public health goals. CONCLUSION: Despite being hailed as a
      "watershed in international trade", the Doha Declaration and Paragraph 6 decision
      have not resolved the problem of access to affordable medicines. The way forward
      must begin with a simplification of their content, to enable actual
      implementation. More fundamentally, once agreed, public health protections under
      TRIPS must be recognised as taking precedent over measures subsequently adopted
      under other trade agreements. This requires, above all, setting aside such
      protections as a basic need and shared goal from trade negotiations at all
      levels.

PMID- 17524148
TI  - A hybrid multiscale Monte Carlo algorithm (HyMSMC) to cope with disparity in time
      scales and species populations in intracellular networks.
AB  - BACKGROUND: The fundamental role that intrinsic stochasticity plays in cellular
      functions has been shown via numerous computational and experimental studies. In
      the face of such evidence, it is important that intracellular networks are
      simulated with stochastic algorithms that can capture molecular fluctuations.
      However, separation of time scales and disparity in species population, two
      common features of intracellular networks, make stochastic simulation of such
      networks computationally prohibitive. While recent work has addressed each of
      these challenges separately, a generic algorithm that can simultaneously tackle
      disparity in time scales and population scales in stochastic systems is currently
      lacking. In this paper, we propose the hybrid, multiscale Monte Carlo (HyMSMC)
      method that fills in this void. RESULTS: The proposed HyMSMC method blends
      stochastic singular perturbation concepts, to deal with potential stiffness, with
      a hybrid of exact and coarse-grained stochastic algorithms, to cope with
      separation in population sizes. In addition, we introduce the computational
      singular perturbation (CSP) method as a means of systematically partitioning fast
      and slow networks and computing relaxation times for convergence. We also propose
      a new criteria of convergence of fast networks to stochastic low-dimensional
      manifolds, which further accelerates the algorithm. CONCLUSION: We use several
      prototype and biological examples, including a gene expression model displaying
      bistability, to demonstrate the efficiency, accuracy and applicability of the
      HyMSMC method. Bistable models serve as stringent tests for the success of
      multiscale MC methods and illustrate limitations of some literature methods.

PMID- 17524143
TI  - A first step in understanding an invasive weed through its genes: an EST analysis
      of invasive Centaurea maculosa.
AB  - BACKGROUND: The economic and biological implications of plant invasion are
      overwhelming; however, the processes by which plants become successful invaders
      are not well understood. Limited genetic resources are available for most
      invasive and weedy species, making it difficult to study molecular and genetic
      aspects that may be associated with invasion. RESULTS: As an initial step towards
      understanding the molecular mechanisms by which plants become invasive, we have
      generated a normalized Expressed Sequence Tag (EST) library comprising seven
      invasive populations of Centaurea maculosa, an invasive aster in North America.
      Seventy-seven percent of the 4423 unique transcripts showed significant
      similarity to existing proteins in the NCBI database and could be grouped based
      on gene ontology assignments. CONCLUSION: The C. maculosa EST library represents
      an initial step towards looking at gene-specific expression in this species, and
      will pave the way for creation of other resources such as microarray chips that
      can help provide a view of global gene expression in invasive C. maculosa and its
      native counterparts. To our knowledge, this is the first published set of ESTs
      derived from an invasive weed that will be targeted to study invasive behavior.
      Understanding the genetic basis of evolution for increased invasiveness in exotic
      plants is critical to understanding the mechanisms through which exotic invasions
      occur.

PMID- 17524149
TI  - A population study of the minicircles in Trypanosoma cruzi: predicting guide RNAs
      in the absence of empirical RNA editing.
AB  - BACKGROUND: The structurally complex network of minicircles and maxicircles
      comprising the mitochondrial DNA of kinetoplastids mirrors the complexity of the
      RNA editing process that is required for faithful expression of encrypted
      maxicircle genes. Although a few of the guide RNAs that direct this editing
      process have been discovered on maxicircles, guide RNAs are mostly found on the
      minicircles. The nuclear and maxicircle genomes have been sequenced and assembled
      for Trypanosoma cruzi, the causative agent of Chagas disease, however the
      complement of 1.4-kb minicircles, carrying four guide RNA genes per molecule in
      this parasite, has been less thoroughly characterised. RESULTS: Fifty-four CL
      Brener and 53 Esmeraldo strain minicircle sequence reads were extracted from T.
      cruzi whole genome shotgun sequencing data. With these sequences and all
      published T. cruzi minicircle sequences, 108 unique guide RNAs from all known T.
      cruzi minicircle sequences and two guide RNAs from the CL Brener maxicircle were
      predicted using a local alignment algorithm and mapped onto predicted or
      experimentally determined sequences of edited maxicircle open reading frames. For
      half of the sequences no statistically significant guide RNA could be assigned.
      Likely positions of these unidentified gRNAs in T. cruzi minicircle sequences are
      estimated using a simple Hidden Markov Model. With the local alignment
      predictions as a standard, the HMM had an ~85% chance of correctly identifying at
      least 20 nucleotides of guide RNA from a given minicircle sequence. Inter
      minicircle recombination was documented. Variable regions contain species
      specific areas of distinct nucleotide preference. Two maxicircle guide RNA genes
      were found. CONCLUSION: The identification of new minicircle sequences and the
      further characterization of all published minicircles are presented, including
      the first observation of recombination between minicircles. Extrapolation
      suggests a level of 4% recombinants in the population, supporting a relatively
      high recombination rate that may serve to minimize the persistence of gRNA
      pseudogenes. Characteristic nucleotide preferences observed within variable
      regions provide potential clues regarding the transcription and maturation of T.
      cruzi guide RNAs. Based on these preferences, a method of predicting T. cruzi
      guide RNAs using only primary minicircle sequence data was created.

PMID- 17524150
TI  - Incidental parasitic infestations in surgically removed appendices: a
      retrospective analysis.
AB  - BACKGROUND: Appendiceal parasites can cause symptoms of appendiceal pain,
      independent of microscopic evidence of acute inflammation. The diagnosis of a
      parasitic infestation is generally achieved only after the pathologic examination
      of the resected appendices. PATIENTS/METHODS: Pathology department records were
      reviewed for all patients who required an operation for symptoms of acute
      appendicitis between 2000 and 2006. The specimens which were pathologically
      diagnosed to contain parasites were reevaluated for features of acute
      inflammation, and parasite type. The medical records were reviewed in detail to
      achieve a diagnostic score(Eskelinen). Radiologic imaging findings were
      correlated, if present. RESULTS: Of the 190 appendectomies performed, 6 specimens
      (3,15%) were found to contain parasites(4 Enterobius vermicularis, 2 Taenia
      subspecies). Appendectomies with Taenia showed acute inflammation, while acute
      inflammation was absent in the ones with Enterobius vermicularis. The Eskelinen
      score was higher than the threshold in two cases with an acute inflammation, and
      in two without. Ultrasound scans, and a computed tomography scan were performed
      in 5 patients. In 3 of 4 bland appendices, results favored acute appendicitis.
      CONCLUSION: The diagnosis of gastrointestinal parasites is not only made by
      examining the stool but the diagnosis can be made by histology from surgical
      specimens. Timely diagnosis and appropriate therapy might prevent probable future
      complications that may necessitate surgical procedures, at least in some of the
      patients. The clinical management of these infections is different from that for
      classical appendicitis.

PMID- 17524151
TI  - Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the
      macrolide antibiotic roxithromycin in human respiratory epithelial cells.
AB  - BACKGROUND: Sulfur mustard (SM) is a potent chemical vesicant warfare agent that
      remains a significant military and civilian threat. Inhalation of SM gas causes
      airway inflammation and injury. In recent years, there has been increasing
      evidence of the effectiveness of macrolide antibiotics in treating chronic airway
      inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory
      effects of a representative macrolide antibiotic, roxithromycin, were tested in
      vitro using SM-exposed normal human small airway epithelial (SAE) cells and
      bronchial/tracheal epithelial (BTE) cells. Cell viability, expression of
      proinflammatory cytokines including interleukin (IL)-1beta, IL-6, IL-8 and tumor
      necrosis factor (TNF), and expression of inducible nitric oxide synthase (iNOS)
      were examined, since these proinflammatory cytokines/mediators are import
      indicators of tissue inflammatory responses. We suggest that the influence of
      roxithromycin on SM-induced inflammatory reaction could play an important
      therapeutic role in the cytotoxicity exerted by this toxicant. RESULTS: MTS assay
      and Calcein AM/ethidium homodimer (EthD-1) fluorescence staining showed that
      roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also,
      roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory
      cytokines IL-1beta, IL-6, IL-8 and TNF at both the protein level and the mRNA
      level, as measured by either enzyme-linked immunosorbent assay (ELISA) or real
      time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression
      of iNOS, as revealed by immunocytochemical analysis using quantum dots as the
      fluorophore. CONCLUSION: The present study demonstrates that roxithromycin has
      inhibitory effects on the cytotoxicity and inflammation provoked by SM in human
      respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated
      cells likely depends on the ability of the macrolide to down-regulate the
      production of proinflammatory cytokines and/or mediators. The results obtained in
      this study suggest that macrolide antibiotics may serve as potential vesicant
      respiratory therapeutics through mechanisms independent of their antibacterial
      activity.

PMID- 17524152
TI  - Quality of life can both influence and be an outcome of general health
      perceptions after heart surgery.
AB  - BACKGROUND: Our aim was to investigate the existence of a reciprocal relationship
      between patients' assessment of quality of life and their appraisal of health. If
      present, this relationship will interfere with the interpretation of heart
      surgery's effect on overall quality of life. METHODS: Path analysis was used to
      investigate reciprocal causal relationships between general health perceptions
      and overall quality of life before and after heart surgery. Longitudinal data
      from a study of coronary artery bypass surgery were used to model lagged, cross
      lagged, and simultaneous paths over four time-points of assessment from before
      surgery to one year afterwards. The conceptual framework for the analysis was the
      Wilson and Cleary causal pathway model. General health perceptions were measured
      with the Short Form 36. Overall quality of life was measured with i) a single
      question regarding life satisfaction and ii) the multi-item Quality of Life
      Survey. RESULTS: Acceptable model fit was obtained for reciprocal causation
      between general health perceptions and overall quality of life. Regression
      coefficients changed over different phases of rehabilitation. Serial correlation
      accounted for much of the variance within variables over time. CONCLUSION: The
      present analysis demonstrates that unidirectional models of causality are
      inadequate to explain the effect of heart surgery on overall quality of life.
      Overall quality of life can causally influence as well as be an outcome of health
      status after coronary artery bypass surgery.

PMID- 17524153
TI  - Pupal diapause of Helicoverpa armigera (Lepidoptera: Noctuidae): sensitive stage
      for thermal induction in the Okayama (western Japan) population.
AB  - Helicoverpa armigera (Hubner) exhibits a facultative pupal diapause, which
      depends on temperature and photoperiod. Pupal diapause is induced at 20 degrees C
      by short photoperiods and inhibited by long photoperiods during the larval stage.
      However, in some pupae (35% of males and 57% of females) of a non-selected field
      population from Okayama Prefecture (34.6 degrees N), diapause is not induced by
      short photoperiods. In the present experiment, the importance of temperature for
      diapause induction was studied in the non-diapausing strain, which was selected
      from such individuals reared at 20 degrees C under a short photoperiod of
      10L:14D. Furthermore, the sensitive stage for thermal determination of pupal
      diapause was determined by transferring larvae of various instars and pupae
      between 20 degrees C and 15 degrees C. Diapause was induced by 15 degrees C
      without respect to photoperiod. When larvae or pupae reared from eggs at 20
      degrees C under a short or a long photoperiod were transferred to 15 degrees C in
      the periods of the middle fifth instar to the first three days after pupation,
      the diapause induction rate was significantly reduced in both males and females,
      especially in females. In contrast, when larvae or pupae reared at 15 degrees C
      were transferred to 20 degrees C in the same periods, diapause was induced in
      males, but not in females. However, the diapause induction rate of pupae
      transferred to 20 degrees C on the fourth day after pupation was significantly
      increased in females. The results show that temperature is the major diapause cue
      in the photoperiod-insensitive strain and the periods of middle fifth larval
      instar to early pupal stage are the thermal sensitive stages for pupal diapause
      induction with some different responses to temperatures between males and females
      in H. armigera.

PMID- 17524154
TI  - Genetic structure and molecular variability of Spodoptera frugiperda
      (Lepidoptera: Noctuidae) collected in maize and cotton fields in Brazil.
AB  - The purpose of this research was to evaluate the genetic similarity and structure
      of the fall armyworm, Spodoptera frugiperda (J.E. Smith), populations associated
      with maize and cotton crops in Brazil using amplified fragment length
      polymorphisms. Mean genetic similarity among populations was 0.45. The unweighted
      pair group method with arithmetic mean analysis dendrograms did not separate
      populations of S. frugiperda into clusters related to the host plant in which the
      insects were collected. No genetic variation was observed among maize and cotton
      populations of S. frugiperda, suggesting that the same populations are injuring
      both crops in Brazil. This research validates the need for stewardship of crop
      protection methods for managing S. frugiperda to reduce the incidence of
      pesticide resistance, due to the spatial and temporal overlapping of maize and
      cotton crops in some regions in Brazil.

PMID- 17524155
TI  - Psyttalia ponerophaga (Hymenoptera: Braconidae) as a potential biological control
      agent of olive fruit fly Bactrocera oleae (Diptera: Tephritidae) in California.
AB  - The olive fruit fly, Bactrocera oleae (Rossi), is a newly invasive, significant
      threat to California's olive industry. As part of a classical biological control
      programme, Psyttalia ponerophaga (Silvestri) was imported to California from
      Pakistan and evaluated in quarantine. Biological parameters that would improve
      rearing and field-release protocols and permit comparisons to other olive fruit
      fly biological control agents were measured. Potential barriers to the successful
      establishment of P. ponerophaga, including the geographic origins of parasitoid
      and pest populations and constraints imposed by fruit size, were also evaluated
      as part of this investigation. Under insectary conditions, all larval stages
      except neonates were acceptable hosts. Provided a choice of host ages, the
      parasitoids' host-searching and oviposition preferences were a positive function
      of host age, with most offspring reared from hosts attacked as third instars.
      Immature developmental time was a negative function of tested temperatures,
      ranging from 25.5 to 12.4 days at 22 and 30 degrees C, respectively. Evaluation
      of adult longevity, at constant temperatures ranging from 15 to 34 degrees C,
      showed that P. ponerophaga had a broad tolerance of temperature, living from 3 to
      34 days at 34 and 15 degrees C, respectively. Lifetime fecundity was 18.7 +/- 2.8
      adult offspring per female, with most eggs deposited within 12 days after adult
      eclosion. Olive size affected parasitoid performance, with lower parasitism
      levels on hosts feeding in larger olives. The implications of these findings are
      discussed with respect to field manipulation and selection of parasitoid species
      for olive fruit fly biological control in California and worldwide.

PMID- 17524156
TI  - Temporal and spatial incidence of alleles conferring knockdown resistance to
      pyrethroids in the peach-potato aphid, Myzus persicae (Hemiptera: Aphididae), and
      their association with other insecticide resistance mechanisms.
AB  - The peach-potato aphid, Myzus persicae (sulzer), is an important arable pest
      species throughout the world. Extensive use of insecticides has led to the
      selection of resistance to most chemical classes including organochlorines,
      organophosphates, carbamates and pyrethroids. Resistance to pyrethroids is often
      the result of mutations in the para-type sodium channel protein (knockdown
      resistance or kdr). In M. persicae, knockdown resistance is associated with two
      amino-acid substitutions, L1014F (kdr) and M918T (super-kdr). In this study, the
      temporal and spatial distributions of these mutations, diagnosed using an allelic
      discriminating polymerase chain reaction assay, were investigated alongside other
      resistance mechanisms (modified acetylcholinesterase (MACE) and elevated
      carboxylesterases). Samples were collected from the UK, mainland Europe, Zimbabwe
      and south-eastern Australia. The kdr mutation and elevated carboxylesterases were
      widely distributed and recorded from nearly every country. MACE and super-kdr
      were widespread in Europe but absent from Australian samples. The detection of a
      strongly significant heterozygote excess for both kdr and super-kdr throughout
      implies strong selection against individuals homozygous for these resistance
      mutations. The pattern of distribution found in the UK seemed to indicate strong
      selection against the super-kdr (but not the kdr) mutation in any genotype, in
      the absence of insecticide pressure. There was a significant association (linkage
      disequilibrium) between different resistance mechanisms, which was probably
      promoted by a lack of recombination due to parthenogenesis.

PMID- 17524157
TI  - Distribution of common genotypes of Myzus persicae (Hemiptera: Aphididae) in
      Greece, in relation to life cycle and host plant.
AB  - Microsatellite genotyping was used to identify common clones in populations of
      the Myzus persicae group from various hosts and regions in mainland Greece and
      southern Italy and to compare their distribution and occurrence on tobacco and
      other crops. Common clones were defined as genotypes collected at more than one
      time or in more than one population; and, therefore, unlikely to be participating
      in the annual sexual phase on peach. Sixteen common genotypes were found,
      accounting for 49.0% of the 482 clonal lineages examined. Eight of these
      genotypes were subjected, in the laboratory, to short days and found to continue
      parthenogenetic reproduction, i.e. they were anholocyclic. Four of the six
      commonest genotypes were red, and one of these accounted for 29.6% of the samples
      from tobacco and 29.4% of those from overwintering populations on weeds. All six
      commonest genotypes were found on weeds and five of them both on tobacco and on
      other field crops. In mainland Greece, the distribution of common clones
      corresponded closely with that of anholocyclic lineages reported in a previous
      study of life cycle variation. Common genotypes were in the minority in the
      commercial peach-growing areas in the north, except on weeds in winter and in
      tobacco seedbeds in early spring, but predominated further south, away from peach
      trees. This contrasts with the situation in southern Italy, reported in a
      previous paper, where peaches were available for the sexual phase, yet all
      samples from tobacco were of common genotypes.

PMID- 17524158
TI  - Statistical models to evaluate invertebrate-plant trophic interactions in arable
      systems.
AB  - Over the past 40 years there have been marked shifts in arable farmland
      management that are widely believed to have had a considerable impact on
      flowering plants and invertebrates and the small mammals and birds that rely upon
      them. It is not yet possible to predict the dynamics of plants and invertebrates
      either with past or future changes in farmland management. This study
      investigates whether a basic invertebrate classification, formed of broad trophic
      groups, can be used to describe interactions between invertebrates and their
      resource plants and evaluate management impacts for genetically modified,
      herbicide-tolerant (GMHT) and conventional herbicide management in both spring-
      and winter-sown oilseed rape. It is argued that the analyses validate trophic
      based approaches for describing the dynamics of invertebrates in farmland and
      that linear models might be used to describe the changes in invertebrate trophic
      group abundance in farmland when driven by primary producer abundance or biomass
      and interactions between invertebrates themselves. The analyses indicate that
      invertebrate dynamics under GMHT management are not unique, but similar to
      conventional management occurring over different resource ranges, and that
      dynamics differed considerably between spring- and winter-sown oilseed rape.
      Thus, herbicide management was of much lower impact on trophic relationships than
      sowing date. Results indicate that invertebrate dynamics in oilseed rape are
      regulated by a combination of top-down and bottom-up trophic processes.

PMID- 17524159
TI  - Utilizing the assassin bug, Pristhesancus plagipennis (Hemiptera: Reduviidae), as
      a biological control agent within an integrated pest management programme for
      Helicoverpa spp. (Lepidoptera: Noctuidae) and Creontiades spp. (Hemiptera:
      Miridae) in cotton.
AB  - Helicoverpa spp. and mirids, Creontiades spp., have been difficult to control
      biologically in cotton due to their unpredictable temporal abundance combined
      with a cropping environment often made hostile by frequent usage of broad
      spectrum insecticides. To address this problem, a range of new generation
      insecticides registered for use in cotton were tested for compatibility with the
      assassin bug, Pristhesancus plagipennis (Walker), a potential biological control
      agent for Helicoverpa spp. and Creontiades spp. Indoxacarb, pyriproxifen,
      buprofezin, spinosad and fipronil were found to be of low to moderate toxicity on
      P. plagipennis whilst emamectin benzoate, abamectin, diafenthiuron, imidacloprid
      and omethaote were moderate to highly toxic. Inundative releases of P.
      plagipennis integrated with insecticides identified as being of low toxicity were
      then tested and compared with treatments of P. plagipennis and the compatible
      insecticides used alone, conventionally sprayed usage practice and an untreated
      control during two field experiments in cotton. The biological control provided
      by P. plagipennis nymphs when combined with compatible insecticides provided
      significant (P<0.001) reductions in Helicoverpa and Creontiades spp. on cotton
      and provided equivalent yields to conventionally sprayed cotton with half of the
      synthetic insecticide input. Despite this, the utilization of P. plagipennis in
      cotton as part of an integrated pest management programme remains unlikely due to
      high inundative release costs relative to other control technologies such as
      insecticides and transgenic (Bt) cotton varieties.

PMID- 17524160
TI  - Genetic differentiation of Culex pipiens (Diptera: Culicidae) in China.
AB  - The population genetic structures of Culex pipiens Linnaeus were evaluated in
      China over a 2000 km transect that encompasses the two subspecies, C. p. pallens
      and C. p. quinquefasciatus. Four polymorphic allozyme loci were investigated in
      1376 mosquitoes sampled from 20 populations across four provinces. These loci
      were not statistically dependent with no apparent heterozygote deficit or excess.
      On a regional scale (intra-province), a low (Fst=0.007-0.016) and significant
      genetic differentiation was found, with no clear geographical pattern. On a wider
      scale (inter-province), the genetic differentiation was higher (Fst=0.059), and
      an isolation by distance emerged. The results are compared with previous
      population genetic surveys of this mosquito species in different geographic areas
      over the world. The overall pattern suggests that Culex pipiens requires
      considerable distance (500-1000 km) to show isolation by distance, irrespective
      of the subspecies (C. p. pipiens, C. p. quinquefasciatus and C. p. pallens) or
      the geographic location.

PMID- 17524161
TI  - Genetic variation among Mediterranean populations of Sesamia nonagrioides
      (Lepidoptera: Noctuidae) as revealed by RFLP mtDNA analysis.
AB  - Restriction fragment length polymorphism analysis of two segments of
      mitochondrial DNA (COI and 16S rRNA) was used to examine genetic variation in
      Sesamia nonagrioides (Lefebvre) populations from the Mediterranean basin. Four
      populations were collected from central and southern Greece, and five from
      northern latitudes: Greece, Italy, France and Spain. No variation was observed in
      COI, while 16S rRNA segment proved highly polymorphic and 28 different haplotypes
      were found. Lower intra-population polymorphism was found in the northern
      populations than in southern ones. Although no significant isolation by distance
      was found, the UPGMA tree based on Nei's raw number of nucleotide differences
      separated the populations into two major groups, i.e. one with the northern (40.6
      degrees N-43.4 degrees N) and the other with the southern populations (37.3
      degrees N-39.2 degrees N). Analysis of molecular variance revealed that most of
      the variation was between the two major groups (Phi(CT)=0.559), and all pairwise
      comparisons between the northern and southern populations resulted in high and
      significant F(ST) values (overall F(ST)=0.604). The high F(ST) values and the
      strong spatial genetic structure indicate that long-distance migration may be a
      rare event. The populations do not seem to have experienced a strong historical
      bottleneck. The occurrence of a few widespread haplotypes and the genetic
      similarity of the northern populations could be attributed to a historical
      expansion of certain haplotypes from the south towards to the northern borders of
      the species' distribution area.

PMID- 17524162
TI  - Supplemental food affects thrips predation and movement of Orius laevigatus
      (Hemiptera: Anthocoridae) and Neoseiulus cucumeris (Acari: Phytoseiidae).
AB  - Two experiments were done to examine the predation of thrips, and the movement of
      Orius laevigatus Fieber and Neoseiulus cucumeris (Oudemans) in the presence and
      absence of two supplemental food sources, pollen and the fungus Trichoderma
      viride. The presence of pollen led to a 55% reduction in predation of the thrips
      by N. cucumeris and a 40% reduction in thrips predation by O. laevigatus, in
      experiments using single predators. The presence of fungus had no significant
      effect on thrips predation by either of the natural enemy species. Movement of
      the natural enemies was examined in a multiple predator experiment, and this
      showed that O. laevigatus was more likely to remain on the plant in the presence
      of thrips and when supplemental food, either pollen or fungus, was present. For
      N. cucumeris, there was no association between the presence of thrips and the
      mite, with the majority of the mites being found on the leaves where pollen was
      present. Although the single and multiple predator experiments were done at
      different times, the indications are that the predation rates of the N. cucumeris
      do not differ greatly between the two experiments, suggesting that there may be a
      potential interference effect between the mites, which is not present for O.
      laevigatus. The significance of these results for the use of supplemental food
      sources in biological control is discussed.

PMID- 17524163
TI  - Treating hop plants with (Z)-jasmone increases colonization by Phorodon humuli
      (Hemiptera: Aphididae) spring migrants.
AB  - Hop plants were sprayed with (Z)-jasmone, at a rate of 50 g ha(-1), during the
      spring migration of the damson-hop aphid Phorodon humuli (Schrank) in 2002 and
      2003. Numbers of P. humuli spring migrants colonizing hop plants, Humulus lupulus
      L., 2-6 and 7-11 days after applying this treatment were assessed in both years.
      During the first five-day period, significantly more spring migrants were found
      on hop plants treated with (Z)-jasmone, in comparison with control plants, in
      2002. By contrast, no significant difference was evident in the second five-day
      period. Although the migration in 2003 was much lighter than in 2002, greater
      numbers of migrants were again removed from treated plants. Indeed, more spring
      migrants were removed from plants sprayed with (Z)-jasmone in this year during
      both five-day periods (11 and 44%, respectively) compared with the 23% greater
      numbers removed in the first five-day period in 2002. Therefore, unlike some
      other species of aphid, where numbers were consistently lower on plots sprayed
      with (Z)-jasmone, spraying the secondary host of P. humuli with this compound
      appears to increase colonization by spring migrants.

PMID- 17524164
TI  - Termite colony ontogeny: supplemental data in the long-term assessment of
      reproductive lifespan, female neotenic production and colony size in
      Reticulitermes flavipes (Isoptera: Rhinotermitidae).
AB  - Reticulitermes flavipes (Kollar) colonies established by field-collected alates
      were reared in the laboratory for 11 years. Weights of members of each caste and
      full-colony censuses were performed regularly; the most recent 2003-2004 data are
      reported. Colonies averaged 11623.5 +/- 910 individuals, and with the exception
      of primary queens from one genetic lineage, mean weights for all castes had
      increased since 2001. Female replacement reproductives, or neotenics, developed
      to replace dead queens in clusters of either few, large individuals or many,
      small individuals. Regardless of cluster size, female neotenics comprised more
      reproductive biomass per colony than primary queens. The number and size of
      female neotenics was independent of colony size or time elapsed since a founding
      queen's death.

PMID- 17524165
TI  - Management of chondrodermatitis nodularis chronica helicis using a 'doughnut
      pillow'.
AB  - Chondrodermatitis nodularis chronica helicis is a well-recognised painful
      condition of the pinna. There have been several modes of treatment described for
      this condition. Although the most common mode of treatment is surgery,1,2 several
      conservative approaches have also been tried. OBJECTIVES: To determine if
      chondrodermatitis nodularis chronica helicis can be treated conservatively using
      a doughnut-shaped pillow. DESIGN AND SETTING: Prospective study in Wrexham Maelor
      Hospital, which is a district general hospital. PARTICIPANTS: All the patients
      clinically diagnosed with chondrodermatitis nodularis chronica helicis between
      September 2003 and September 2004. All such patients were seen by an ENT
      consultant with a special interest in facial lesions. Patients who could not be
      clinically diagnosed with chondrodermatitis nodularis chronica helicis were
      excluded from the study. MAIN OUTCOME MEASURE: Pain relief following the use of a
      doughnut pillow was used as the main outcome measure. RESULTS: Twenty-three (14
      female and 9 male) patients were treated with a special doughnut-shaped pillow
      designed to relieve the pressure on the affected ear. Of the 23 lesions treated
      13 remained pain free after a follow-up period of one year. CONCLUSION:
      Conservative treatment of chondrodermatitis nodularis chronica helicis using a
      doughnut pillow is very cost effective.

PMID- 17524166
TI  - Paeoniflorin inhibits TGF-beta1-mediated collagen production by Schistosoma
      japonicum soluble egg antigen in vitro.
AB  - The main pathological characteristics of hepatic fibrosis in schistosomiasis are
      the proliferation of hepatic stellate cells (HSCs) and the deposition of collagen
      type I (Col I) and collagen type III (Col III). Transforming growth factor beta-1
      (TGF-beta1) plays an important role in hepatic fibrosis. Paeoniflorin (PAE) has
      been reported to have immunoregulatory effects; however, the mechanism of its
      anti-hepatic fibrosis in S. japonicum has not been elucidated. In the present
      study, we found that mouse peritoneal macrophages (PMphis) stimulated by soluble
      egg antigen (SEA) of S. japonicum could secrete TGF-beta1, and the TGF-beta1 in
      the peritoneal macrophage-conditioned medium (PMCM) could induce proliferation of
      HSCs and secretion of Col I and III. We selected PMCM at 1 : 2 dilution as the
      optimum PMCM (OPMCM). Then we treated HSCs pre-incubated with OPMCM with PAE, and
      found that the inhibition of HSC proliferation or Col I and III production were
      closely correlated with the concentration of PAE. Further investigation found
      that PAE significantly decreased the Smad3 transcription and phosphorylation in
      HSCs stimulated by OPMCM. In conclusion, SEA plays a key role in hepatic fibrosis
      by inducing TGF-beta1 from PMphis. PAE can exert anti-fibrogenic effects by
      inhibiting HSCs proliferation and down-regulating Smad3 expression and
      phosphorylation through TGF-beta1 signalling.

PMID- 17524167
TI  - The role of the Wilms tumour gene (WT1) in normal and malignant haematopoiesis.
AB  - In addition to its loss playing a pivotal role in the development of a childhood
      kidney malignancy, the Wilms tumour 1 gene (WT1) has emerged as an important
      factor in normal and malignant haematopoiesis. Preferentially expressed in CD34+
      haematopoietic progenitors and down-regulated in more-differentiated cells, the
      WT1 transcription factor has been implicated in regulation of apoptosis,
      proliferation and differentiation. Putative target genes, such as BCL2, MYC, A1
      and cyclin E, may cooperate with WT1 to modulate cell growth. However, the
      effects of WT1 on target gene expression appear to be isoform-specific. Certain
      WT1 isoforms are over-represented in leukaemia, but the exact mechanisms
      underlying the role of WT1 in transformation remain unclear. The ubiquity of WT1
      in haematological malignancies has led to efforts to exploit it as a marker for
      minimal residual disease and as a prognostic factor, with conflicting results. In
      vitro killing of tumour cells by WT1-specific CD8+ cytotoxic T lymphocytes
      facilitated design of Phase I vaccine trials that showed clinical regression of
      WT1-positive tumours. Alternative methods employing WT1-specific immunotherapy
      are being investigated and might ultimately be used to optimise multimodal
      therapy of haematological malignancies.

PMID- 17524168
TI  - Dietary patterns and their correlates among middle-aged and elderly Chinese men:
      a report from the Shanghai Men's Health Study.
AB  - Dietary patterns, which reflect the complexity of food preference, lifestyle and
      socio-economic status, may play a major role in health and longevity.
      Understanding dietary patterns and their correlates is important to the research
      of diet and health relationships. In the Shanghai Men's Health Study (SMHS) a
      total of 61,582 men aged 40-74 were recruited between 2002 and 2006. Their food
      intake over the previous year was collected using a validated FFQ. Study
      participants (75.6%) reported little or no change in meat and vegetable intake in
      the 5 years prior to recruitment. Using the baseline data of the SMHS, we
      assessed dietary patterns, as well as their relationship with socio-demographic
      and lifestyle factors and with prevalence of some chronic diseases. Three major
      dietary patterns, fruit-, vegetable- and meat-based diets, were identified in our
      population. Consumption of the fruit diet appeared to be more common among men
      who were older and more physically active, had higher income, and lower waist-to
      hip ratio (WHR), while this diet was less common among manual labourers. The meat
      or vegetable-based diets were less common among elderly men and more common
      among men with higher WHR. Dietary patterns appeared to be associated with the
      presence of health conditions. In general, subjects with a chronic disease were
      more likely to have the vegetable-based diet and less likely to have the fruit-
      or meat-based diets. Future studies of diet and health in this population will
      need to carefully take into account these potential confounders.

PMID- 17524169
TI  - What proportion of patients referred to an otolaryngology vertigo clinic have an
      otological cause for their symptoms?
AB  - BACKGROUND: Dizziness is a common and often complex complaint. Between nine and
      13 per cent of patients seen in general practice are referred to a variety of
      specialist clinics. The diagnoses and outcomes of these referrals are seldom
      reported. AIMS: To determine the proportion of patients referred to an otology
      led vertigo clinic in whom an otological cause for vertigo could be identified.
      DESIGN OF STUDY: Prospective cohort study of consecutive new clinic attendees
      over one year. SETTING AND METHODS: Otology led vertigo clinic in an urban
      teaching hospital in England. Patients' details including age, sex, referring
      clinician, investigations, diagnoses, treatment and final outcome were recorded
      in an anonymised database. RESULTS: 91 new patients, 31 men and 60 women with a
      mean age of 52.6 years (range 16-81) were seen. General practitioners referred 87
      per cent of the patients. Twenty-seven patients underwent further investigations
      including imaging, electronystagmography and other audiological tests. A
      labyrinthine disorder accounted for 50 per cent of the diagnoses. Meniere's
      disease or a variant was diagnosed in 20 patients (21 per cent). Fifty-six
      patients (61 per cent) reported resolution of or improvement in their symptoms.
      Thirty-one patients (34 per cent) were asymptomatic and free of abnormal findings
      on initial attendance and were discharged from hospital care. CONCLUSIONS: Forty
      six patients (50.6 per cent, 95 per cent confidence interval, 40.4-60.6 per cent)
      had vertigo due to an otological disorder. The selection of an otolaryngology
      based vertigo clinic by the general practitioner for initial referral seems
      appropriate.

PMID- 17524171
TI  - Acquired immunodeficiency syndrome related Kaposi's sarcoma eroding the maxillary
      bone.
AB  - BACKGROUND: Oral involvement is a common manifestation of acquired
      immunodeficiency syndrome related Kaposi's sarcoma, and it occurs in
      approximately one-third of afflicted patients. METHODS: We report an unusual case
      of Kaposi's sarcoma of the hard palate which invaded the underlying maxillary
      bone. RESULTS: The patient underwent excisional biopsy and was subsequently
      treated with localised radiation and systemic chemotherapy including liposomal
      doxorubicin. CONCLUSIONS: The presentation, differential diagnosis, radiographic
      appearance and management of this serious complication are discussed. Our case
      highlights the need for a multidisciplinary approach, consisting of ENT, oncology
      and infectious disease consultation, to ensure appropriate management of
      maxillofacial, intraosseous, acquired immunodeficiency syndrome related Kaposi's
      sarcoma.

PMID- 17524170
TI  - ENT manifestations in Iranian patients with primary antibody deficiencies.
AB  - OBJECTIVE: One hundred and nine patients with primary antibody deficiencies were
      selected in order to determine the frequency of ENT complications. METHOD:
      Demographic information and ENT medical histories were collected for each
      patient. Duration of study for each patient was divided into two periods of
      before diagnosis and after diagnosis and the initiation of treatment. RESULTS:
      Eighty-two of 109 patients (75.2 per cent) experienced ENT infections during the
      course of the disease (63: otitis media, 75: sinusitis and nine: mastoiditis). At
      the time of diagnosis, 52 (47.7 per cent) out of 109 patients presented with an
      ENT symptom. The frequencies of episodes were 27 for sinusitis and 25 for otitis
      media (one complicated with mastoiditis). After immunoglobulin replacement
      therapy the incidence of otitis media was reduced from 1.75 before treatment to
      0.39 after treatment per patient per year (p = 0.008). The incidence of sinusitis
      also significantly decreased from 2.38 to 0.78 (p value = 0.011). CONCLUSION: ENT
      infections are common medical problems in primary antibody deficiency patients.
      Persistent and recurrent ENT infections should be suspected as originating from a
      possible underlying immunodeficiency.

PMID- 17524172
TI  - Mutational falsetto: intervention outcomes in 45 patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the outcomes of therapeutic
      intervention in patients with mutational falsetto, by applying perceptual and
      acoustic analysis before and after voice therapy. MATERIALS AND METHODS: Forty
      five consecutive patients with mutational falsetto were studied retrospectively.
      Acoustic analysis (i.e. fundamental frequency, jitter, shimmer, and formants one,
      two and three) was performed using the Multi-Dimensional Voice Program.
      Perceptual voice analyses were performed, including graded severity-roughness
      breathiness-aesthenicity-strain assessment. RESULTS: Subjects' fundamental
      frequency, voice formants one, two and three, jitter, and shimmer were greater
      before than after treatment. There were statistically significant differences
      between pre- and post-treatment average values for fundamental frequency, jitter
      and shimmer. There were also statistically significant differences between pre-
      and post-treatment average values for formants one and two. These results were
      maintained after six months of follow up, and there was no significant difference
      between results at three- and six-month follow up. According to perceptual
      evaluation, each subject's voice had altered from mutational falsetto to chest
      voice by completion of the intervention. Thus, all of the patients successfully
      lowered their modal speaking voice to an appropriate level. CONCLUSION: In the
      light of objective evaluations, and by applying the study treatment protocol,
      these results suggest that normal voice can be maintained after intervention, at
      six months' follow up.

PMID- 17524173
TI  - Angiomyoma of buccal vestibule: a rare case with a normal karyotype.
AB  - Angiomyoma is an uncommon, benign, soft tissue tumour characterised by bundles of
      smooth muscle cells intermixed with numerous vascular channels, which usually
      develops in the lower extremities. Oral manifestations are quite rare. Most oral
      cases occur in the lips and tongue; angiomyoma affecting the buccal vestibule is
      very rare. A case of angiomyoma in the buccal vestibule with a normal karyotype
      is reported.

PMID- 17524174
TI  - Malleostapedotomy in tympanosclerosis patients.
AB  - OBJECTIVES: To present our personal experience of a series of 10 patients
      suffering from tympanosclerosis with functional blocking of the stapes or
      footplate, who underwent malleostapedotomy surgery. The criteria for patient
      selection for this type of operation, and its results and complications, are
      discussed. METHODS: Prospective study. RESULTS: Incus and malleus dysfunction was
      observed in 70 per cent of cases, either alone or combined with fixation of the
      stapes. The post-operative hearing results were considered to be satisfactory
      (i.e. within 20 dB) in 80 per cent of cases. Only one patient had sensorineural
      hearing loss over 10 dB. CONCLUSIONS: Malleostapedotomy has proved its
      practicability in the treatment of patients with fixed footplate or stapes
      complicated by ankylosis of the incudomalleolar joint. This procedure can be
      considered a further, valid technique within the otologist's surgical
      armamentarium.

PMID- 17524175
TI  - Side selection for cochlear implantation in a case of Cogan's syndrome.
AB  - Cogan's syndrome is a rare clinical entity that is characterised by non
      syphilitic interstitial keratitis and audiovestibular symptoms. The cause of
      Cogan's syndrome is considered to be autoimmune disease, which is supported by
      the resolution of hearing loss after steroid treatment, and the association with
      other autoimmune diseases. The sensorineural hearing loss of Cogan's syndrome is
      progressive over a few months, and sudden, bilateral deafness often occurs, which
      may be an indication for cochlear implantation. This paper presents the case of a
      young woman suffering from Cogan's syndrome and sudden, bilateral deafness. With
      reference to this case, we describe problems regarding cochlear implantation for
      Cogan's syndrome and radiological findings aiding selection of cochlear
      implantation side.

PMID- 17524176
TI  - Associations between postprandial insulin and blood glucose responses, appetite
      sensations and energy intake in normal weight and overweight individuals: a meta
      analysis of test meal studies.
AB  - It is unclear whether postprandial blood glucose or insulin exerts a regulatory
      function in short-term appetite regulation in humans. The aim of this study was
      to investigate, by use of meta-analysis, the role of blood glucose and insulin in
      short-term appetite sensation and energy intake (EI) in normal weight and
      overweight participants. Data from seven test meal studies were used, including
      136 healthy participants (ALL) (92 normal weight (NW) and 44 overweight or obese
      (OW)). All meals were served as breakfasts after an overnight fast, and appetite
      sensations and blood samples were obtained frequently in the postprandial period.
      Finally, an ad libitum lunch was served. Data were analysed by fixed effects
      study level (SL) meta-regression analysis and individual participant data (IPD)
      regression analysis, using STATA software. In SL analysis, postprandial insulin
      response was associated with decreased hunger in ALL, NW and OW (P < 0.019), and
      with increased satiety in NW (P = 0.004) and lower subsequent EI in OW (P =
      0.022). Multivariate IPD analysis showed similar associations, but only in NW for
      hunger, satiety and EI (P < 0.028), and in ALL for EI (P = 0.016). The only
      association involving blood glucose was the multivariate IPD analysis showing an
      inverse association between blood glucose and EI in ALL (P = 0.032). Our results
      suggest that insulin, but not glucose, is associated with short-term appetite
      regulation in healthy participants, but the relationship is disrupted in the
      overweight and obese. We conclude that the postprandial insulin response may be
      an important satiety signal, and that central nervous system insulin resistance
      in overweight might explain the blunted effect on appetite.

PMID- 17524177
TI  - Effect of phytic acid and microbial phytase on the flow and amino acid
      composition of endogenous protein at the terminal ileum of growing broiler
      chickens.
AB  - The effects of phytic acid and microbial phytase on the flow and composition of
      endogenous protein at the terminal ileum of broiler chickens were investigated
      using the peptide alimentation method. Phytic acid (fed as the sodium salt) was
      included in a synthetic diet at 8.5, 11.5 and 14.5 g/kg (or 2.4, 3.2 and 4.0 g/kg
      phytate-phosphorus) and each diet was fed without or with an Escherichia coli
      derived microbial phytase at 500 phytase units/kg diet. A control containing no
      phytate was fed as a comparison to estimate basal endogenous flows. Ingestion of
      phytic acid increased (P < 0.05) the flow of endogenous amino acids and N by an
      average of 47 % at the lowest phytic acid concentration and 87 % at the highest.
      The addition of microbial phytase reduced (P < 0.05) the inimical effects of
      phytic acid on endogenous amino acid flow at all dietary phytic acid levels. The
      composition of endogenous protein was also influenced (P < 0.10-0.001) by
      increasing phytic acid concentrations and phytase addition. The effects of phytic
      acid and phytase on endogenous flow and composition of endogenous protein,
      however, varied depending on the amino acid. It is concluded that the effects of
      phytase on amino acid digestibility may be mediated, in part, through a route of
      reduced endogenous loss.

PMID- 17524178
TI  - Maternal low-protein diet during lactation programmes body composition and
      glucose homeostasis in the adult rat offspring.
AB  - Previously we have reported that maternal malnutrition during lactation
      programmes body weight and thyroid function in the adult offspring. In the
      present study we evaluated the effect of maternal protein restriction during
      lactation upon body composition and hormones related to glucose homeostasis in
      adult rats. During lactation, Wistar lactating rats and their pups were divided
      into two experimental groups: control (fed a normal diet; 23% protein) and
      protein-restricted (PR; fed a diet containing 8% protein). At weaning, offspring
      received a normal diet until they were 180 d old. Body weight (BW) and food
      intake were monitored. Serum, adrenal glands, visceral fat mass (VFM) and
      carcasses were collected. PR rats showed lower BW (-13%; P < 0.05), VFM (-33%; P
      < 0.05), total body fat (-33%; P < 0.05), serum glucose (-7%; P < 0.05), serum
      insulin (-26%, P < 0.05), homeostasis model assessment index (-20%), but higher
      total adrenal catecholamine content (+90%; P < 0.05) and serum corticosterone
      concentration (+51%; P < 0.05). No change was observed in food intake, protein
      mass or total body water. The lower BW of PR rats is due to a reduction of white
      fat tissue, probably caused by an increase in lipolysis or impairment of
      lipogenesis; both effects could be related to higher catecholaminergic status, as
      well as to hypoinsulinaemia. To conclude, changes in key hormones which control
      intermediary metabolism are programmed by maternal protein restriction during
      lactation, resulting in BW alterations in adult rats.

PMID- 17524179
TI  - Resting energy expenditure in children with neonatal chronic lung disease and
      obstruction of the airways.
AB  - Children with history of broncho-pulmonary dysplasia (BPD) often suffer from
      growth failure and lung sequelae. The main objective of this study was to test
      the role of pulmonary obstruction on resting energy expenditure (REE) and
      nutritional status in BPD. Seventy-one children with BPD (34 boys and 37 girls)
      and 30 controls (20 boys and 10 girls) aged 4-8 years were enrolled. Body
      composition was assessed by bio-impedancemetry measurements; REE was measured by
      indirect calorimetry. Predicted REE was calculated using the Schofield equation.
      The population of children with BPD was divided into three groups: children
      without obstruction of the airways, children with moderate obstruction of the
      airways, and children with severe obstruction. Children with BPD were
      significantly smaller and leaner than controls. Altered body composition
      (reduction of fat mass) was observed in BPD children that suffered from airway
      obstruction. REE was significantly lower in children with BPD compared to
      controls, but when adjusted for weight and fat-free mass no significant
      difference was observed irrespective of pulmonary status. Airway obstruction in
      children with BPD does not appear to be associated with an increased REE.
      Moreover altered REE could not explain the altered nutritional status that is
      still observed in BPD in later childhood. This supports the hypothesis that body
      composition and pulmonary function in BPD in later childhood are fixed sequelae
      originating from the neonatal period.

PMID- 17524180
TI  - Glucose homeostasis remains altered by acute caffeine ingestion following 2 weeks
      of daily caffeine consumption in previously non-caffeine-consuming males.
AB  - Acute caffeine ingestion increases serum NEFA and plasma adrenaline and decreases
      insulin sensitivity. Although frequently suggested, it is not known if a
      tolerance to these alterations in glucose homeostasis is developed in habitual
      caffeine consumers. Our objective was to determine whether acute caffeine
      ingestion continued to alter insulin, glucose, NEFA and adrenaline during an oral
      glucose tolerance test (OGTT) following 14 d of caffeine consumption. Twelve
      caffeine-naive young males underwent four OGTTs over a 4-week period. Subjects
      ingested a gelatin-filled placebo (PLA) capsule on the first trial day and 5 mg
      caffeine/kg body weight on the remaining three trial days (day 0, day 7, day 14)
      before a 2 h OGTT. Following day 0 and day 7, subjects were given six dosages of
      5 mg caffeine/kg to consume per d between trials. Serum insulin and blood glucose
      area under the curve (AUC) were significantly elevated (P < 0.05) v. PLA on day 0
      (36 and 103 %, respectively) and were not different from PLA on day 7. On day 14,
      insulin AUC was 29 % greater than PLA (P < 0.05), and glucose was greater (P <
      0.05) during the first hour, although the 50 % elevation in glucose AUC was not
      different from PLA. Before the OGTT, caffeine resulted in greater (P < 0.05)
      serum NEFA and plasma adrenaline concentrations in all three caffeine trials, but
      both NEFA and adrenaline concentrations were decreased (P < 0.05) on day 14 v.
      day 0. Although 14 d of caffeine consumption by previously caffeine-naive
      subjects reduced its impact on glucose homeostasis, carbohydrate metabolism
      remained disrupted.

PMID- 17524181
TI  - Body fat content and feeding level interact strongly in the short- and medium
      term regulation of plasma leptin during underfeeding and re-feeding in adult
      sheep.
AB  - Circulating leptin is regulated by food intake in the long, medium and short
      term; however, little is known about putative remnant effects of these successive
      regulations at any given time. To clarify this, two experiments were conducted in
      adult sheep, during which body condition parameters and plasma leptin were
      measured. During experiment 1, twenty ewes with normal body condition were either
      well fed (101 % of maintenance energy requirements (MER)) or underfed (41 % MER)
      for 166 d, then rapidly re-fed (at a mean of 208 % MER) for 3 d. Leptinaemia
      decreased after 14 d of underfeeding, remained depressed until day 166 and did
      not increase after 3 d re-feeding, whereas it was increased (+153 %; P < 0.05) by
      re-feeding the previously well-fed ewes. During experiment 2, twenty-four fat or
      lean ewes were either well fed (114 % MER) or underfed (52 % MER) for 94 d, and
      gradually re-fed for 2 d and maintained at a high feeding level (235 % MER) for 9
      d. Underfeeding decreased leptinaemia in fat (from 4.19 to 2.63 ng/ml) but not
      lean ewes, and re-feeding increased leptinaemia after 5 d in lean previously well
      fed (+123 %; P < 0.05) but not underfed ewes. In fat ewes, the impact of re
      feeding was rapid (+144 %; P < 0.001 at 5 d) in previously well-fed ewes, whereas
      it was more gradual with a maximum at 11 d (+162 %; P < 0.01) in previously
      underfed ewes. In conclusion, leptinaemia is modulated by short-term energy
      intake level in interaction with long-term regulations involving nutritional
      history and body fatness, suggesting that a biological threshold of adiposity
      (about 20 %) is necessary to allow short- and medium-term leptin regulation.

PMID- 17524182
TI  - Gonadectomy and high dietary fat but not high dietary carbohydrate induce gains
      in body weight and fat of domestic cats.
AB  - A high concentration of dietary carbohydrate is suggested to increase the risk of
      obesity and diabetes mellitus in domestic cats. To evaluate this, food intake,
      body weight, fat mass and circulating adiposity-related factors were determined
      in twenty-four sexually mature (9-12 months) cats assigned to four six-cat
      dietary groups balanced for body weight and sex. The effect of dietary fat in
      exchange for carbohydrate at 9, 25, 44 and 64 % of metabolisable energy (ME) in a
      purified diet of constant protein:ME ratio was studied 13 weeks before and 17
      weeks after gonadectomy (GX). Body weight did not significantly change among the
      cats before GX except for an increase of 17 (sem 5) % in cats given the highest
      fat diet. Following GX, all groups gained body weight, and body fat mass was
      positively correlated (r 0.50; P < 0.04) with dietary fat percentage. Post-GX
      weight gains were much greater for females (+39 (sem 5) %) than males (+10 (sem
      4) %). Plasma ghrelin concentration negatively correlated (P < 0.02) with dietary
      fat percentage and, before GX, was greater (P < 0.05) in females than males.
      Plasma insulin concentration increased with weight gain induced by high dietary
      fat. Plasma glucose, TAG and leptin concentrations were not affected by dietary
      fat percentage, GX or weight gain. These data provide evidence that in cats, high
      dietary fat, but not carbohydrate, induces weight gain and a congruent increase
      in insulin, while GX increases sensitivity to weight gain induced by dietary fat.

PMID- 17524183
TI  - Dietary oxidised fat up regulates the expression of organic cation transporters
      in liver and small intestine and alters carnitine concentrations in liver, muscle
      and plasma of rats.
AB  - It has been shown that treatment of rats with clofibrate, a synthetic agonist of
      PPARalpha, increases mRNA concentration of organic cation transporters (OCTN)-1
      and -2 and concentration of carnitine in the liver. Since oxidised fats have been
      demonstrated in rats to activate hepatic PPARalpha, we tested the hypothesis that
      they also up regulate OCTN. Eighteen rats were orally administered either
      sunflower-seed oil (control group) or an oxidised fat prepared by heating
      sunflower-seed oil, for 6 d. Rats administered the oxidised fat had higher mRNA
      concentrations of typical PPARalpha target genes such as acyl-CoA oxidase,
      cytochrome P450 4A1 and carnitine palmitoyltransferases-1A and -2 in liver and
      small intestine than control rats (P < 0.05). Furthermore, rats treated with
      oxidised fat had higher hepatic mRNA concentrations of OCTN1 (1.5-fold) and OCTN2
      (3.1-fold), a higher carnitine concentration in the liver and lower carnitine
      concentrations in plasma, gastrocnemius and heart muscle than control rats (P <
      0.05). Moreover, rats administered oxidised fat had a higher mRNA concentration
      of OCTN2 in small intestine (2.4-fold; P < 0.05) than control rats. In
      conclusion, the present study shows that an oxidised fat causes an up regulation
      of OCTN in the liver and small intestine. An increased hepatic carnitine
      concentration in rats treated with the oxidised fat is probably at least in part
      due to an increased uptake of carnitine into the liver which in turn leads to
      reduced plasma and muscle carnitine concentrations. The present study supports
      the hypothesis that nutrients acting as PPARalpha agonists influence whole-body
      carnitine homeostasis.

PMID- 17524184
TI  - Haem and non-haem iron intake through 17 years of adult life of a British Birth
      Cohort.
AB  - An investigation was carried out to determine whether there were significant
      changes in the intake of haem and non-haem Fe of adult men and women in the UK
      from 1982 (aged 36 years) to 1999 (aged 53 years). The 1253 subjects studied were
      members of the Medical Research Council National Survey of Health and
      Development; a longitudinal study of a nationally representative cohort of births
      in 1946. Food intake was recorded in a 5-d diary at age 36 years in 1982, 43
      years in 1989 and 53 years in 1999. Outcome measures were mean intakes of total
      Fe, haem and non-haem Fe, by year, gender and food source. There were significant
      changes in total Fe, haem Fe and non-haem Fe intake over the three time points.
      Total Fe intake was significantly higher in 1989 than in 1982 or 1999 for both
      men and women but haem Fe was significantly lower in 1999 mainly due to a 40%
      fall in haem Fe from beef during this period. Haem Fe from processed meats fell
      by more than 50% between 1989 and 1999 but that from poultry rose by more than
      50%. Cereal foods remained the most important source of non-haem Fe and the
      contribution from breakfast cereals rose relative to that of bread over the 17
      years. Several factors could be responsible for these changes, particularly the
      importance of the epidemic of BSE from 1990. The possible advantages of a lower
      haem Fe intake in older subjects are discussed.

PMID- 17524185
TI  - Partner referral tools and techniques for the clinician diagnosing a sexually
      transmitted infection.
AB  - Public health agencies have insufficient resources to trace and refer to medical
      evaluation the sexual partners of patients with sexually transmitted infections
      (STI). Only a minority of such patients receives formal sex partner referral
      services. Hence this responsibility rests, by default, with the diagnosing
      clinician or with the infected patient. Unfortunately, clinicians do not
      sufficiently appreciate this public health lacuna, and patients with STI usually
      perform poorly at notifying partners. Clinician and patient obstacles to
      successful partner referral are discussed, and brief counselling techniques are
      suggested. Use of patient-delivered therapy, via medication or prescription
      (dispensed with appropriate warnings), probably serves to emphasize the urgency
      and importance of notifying partners. Successful referral to medical attention
      has been shown to help prevent re-infection of the index patient and to curtail
      community transmission.

PMID- 17524186
TI  - Identifying hidden capacity through modernization of genitourinary medicine
      services.
AB  - Rates of sexually transmitted infections have continued to rise in recent years
      throughout the UK. Poor access to genitourinary medicine clinics has been
      highlighted as a major factor contributing to this increase. Despite a lack of
      investment in sexual health services, capacity for new patients has almost
      doubled over the past decade. However, a significant amount of unreleased
      capacity is still available within the service. This 'Six Sigma' study group was
      formed in 2003 to explore whether capacity could be enhanced by further reducing
      the ratio of follow-up to new-case patient visits. Following implementation of
      recommended changes, the mean follow-up to new-case ratio reduced from 0.82
      (range 0.29-1.69) to 0.62 (range: 0.19-1.40). Crucially, this increase in
      capacity was achieved without adversely affecting quality of care. The Six Sigma
      group have developed the tools to release capacity in a controlled and validated
      way and are keen to help other clinics achieve similar results.

PMID- 17524187
TI  - Releasing capacity in sexual health through modernization.
AB  - Increasing rates of sexually transmitted infections (STIs), coupled with a lack
      of investment, have placed mounting pressure on sexual health services. To
      address these growing demands and meet new Government targets for access, the
      British Association for Sexual Health and HIV (BASHH) and other UK bodies are
      keen to promote modernization and innovation within the service. The 'Six Sigma'
      study group was formed in 2003 to investigate whether capacity within
      genitourinary (GU) medicine clinics could be enhanced by further reducing the
      follow-up to new-case patient visit ratio. A process improvement methodology, Six
      Sigma, was employed to achieve these aims. The clinics within the Six Sigma group
      demonstrated a significant reduction in the follow-up to new-case ratio, so
      releasing a considerable amount of additional capacity. Importantly, this group
      developed the tools for other GU medicine clinics to achieve similar results and
      benefit from their considerable expertise.

PMID- 17524188
TI  - Reducing follow-ups: an opportunity to increase the capacity of genitourinary
      medicine services across the UK.
AB  - Significant increases in genitourinary (GU) medicine clinic workloads throughout
      the UK have resulted in an unmet demand for appointments, and increased waiting
      times. In order to meet the government target of a 48-hour maximum waiting time
      for all patients, many clinics are modernising current practices to increase
      capacity and improve access to services. The 'Six Sigma' study group of 12 GU
      medicine clinics which was formed in 2003 to investigate means of enhancing
      capacity of GU medicine services, has demonstrated that there is a significant
      amount of unreleased capacity within UK clinics. In this article, the Six Sigma
      group present potential actions which other GU medicine clinics in the UK may be
      able to apply and thereby release additional capacity. Example case studies from
      the Six Sigma study are also presented, illustrating the applicability of this
      model throughout the UK. The findings of the Six Sigma project offer GU medicine
      clinics across the UK the opportunity to increase capacity, without adversely
      affecting quality of care.

PMID- 17524189
TI  - Bacterial vaginal flora in relation to changing oestrogen levels.
AB  - Hormonal changes may be important in the onset and clearance of bacterial
      vaginosis. We studied vaginal flora and serum oestradiol levels of 55 women at
      baseline and during hormonal treatment. None developed bacterial vaginosis (BV)
      from normal vaginal flora, 69% of women had normal flora at baseline increasing
      to 91% following hormonal treatment. The mean oestradiol level with BV was 39.07
      ng/L compared with 176.41 ng/L with normal flora. Non-smokers had a mean
      oestradiol level of 173.95 ng/L compared with 118.67 ng/L in smokers. Recombinant
      follicle-stimulating hormone resulted in a mean oestradiol rise of 113.9 ng/L.
      The mean rise was 330.4 ng/L with improved vaginal flora but only 15.1 ng/L in
      persistently abnormal or worsening flora. A rise in oestradiol in this group of
      women was associated with a significant reduction of abnormal flora. Reversion
      from BV to normal flora was associated with a greater rise in oestradiol than
      where abnormal flora persisted or worsened. This study supports a possible
      hormonal influence in the natural history of BV. The lower oestradiol levels in
      smokers may help explain their increased risk of BV.

PMID- 17524190
TI  - Correlates of late HIV diagnosis: implications for testing policy.
AB  - To develop new strategies aimed to reduce the delay in seeking HIV diagnosis, we
      proposed to identify correlates of late diagnosis of HIV infection in France.
      Late testing was studied among the 1077 patients diagnosed from 1996 and enrolled
      in the ANRS-EN12-VESPA, a representative sample of the French HIV-infected
      population. Patients were defined as 'late testers' if they had presented either
      clinical AIDS events or CD4 cell count <200/mm(3) at diagnosis. In all, 33.1%
      were classified as late testers, among whom 42.6% had discovered their HIV
      infection at the time of AIDS events. This proportion increased with age and was
      higher for heterosexual men and migrants. Among the non-migrants heterosexual
      population, late diagnosis was more frequent among people in longstanding couple,
      with children and conversely was less likely among individuals with large number
      of sexual partners. Being on welfare benefit before diagnosis was associated with
      a lower risk of late diagnosis. Among migrants, lack of recent steady partnership
      was associated with an increased risk, as being diagnosed during the first year
      of stay in France. Our results showed low risk factors of infection were risk
      factors of late testing. Public communication should aim at improving the
      awareness of HIV risk in longstanding couples with stable employment, both among
      homosexual and heterosexual populations. Among migrants, HIV testing with
      informed consent short after entry should be improved, especially towards
      individuals not in couple.

PMID- 17524191
TI  - Estimating dissemination of Centers for Disease Control and Prevention Sexually
      Transmitted Disease Treatment Guidelines from a survey of physicians.
AB  - Periodically, the Centers for Disease Control and Prevention (CDC) produce
      guidelines for the treatment of sexually transmitted diseases (STDs) in the USA.
      To date, few evaluations of the dissemination of these guidelines exist. A paper
      and pencil survey was distributed via priority mail to a sample of Atlanta-area
      physicians, 416 (34%) of whom responded with complete data. Physicians were drawn
      from private practice, managed-care settings and public settings. In all, 85% of
      respondents treated STD, with a further 10% referring cases. Of those treating
      STD, 56% owned a copy of the 2002 CDC Treatment Guidelines, and 26% knew how to
      access them. The corresponding figures for physicians not treating STD were 25%
      and 30%. Of the physicians who did have copies, half had accessed the internet
      for their copies. Acquisition of, or the knowledge of how to acquire, the CDC STD
      Treatment Guidelines was widespread. The internet may be an effective and cost
      saving means of disseminating the guidelines, although the continued need for
      print distribution should not be discounted.

PMID- 17524192
TI  - Cytomegalovirus viral load testing of blood using quantitative polymerase chain
      reaction in acutely unwell HIV-1-positive patients lacks diagnostic utility.
AB  - We examined the usefulness of measuring cytomegalovirus (CMV) viral load (VL) in
      blood using quantitative polymerase chain reaction (qPCR) in establishing a
      diagnosis of CMV end-organ disease in consecutive unwell HIV-infected patients.
      The indication for testing for CMV, CD4 count, CMV VL and presence of CMV end
      organ disease were abstracted from case-notes. During a 42-month period, 216
      tests were performed in 181 patients; the majority (61%) had CD4 counts <100
      cells/microL. The prevalence of detectable CMV by qPCR was 43.5% (94/216) with a
      prevalence of CMV end-organ disease of 7.4% (16/216). Of patients with CMV
      detectable by qPCR, 72 % (50/69) had CD4 counts <100 cells/microL. For patients
      with definite CMV end-organ disease, the positive predictive value of detectable
      CMV by qPCR was 10% (9/94), and the negative predictive value was 98% (119/122).
      In acutely unwell HIV-infected patients, detection of CMV by qPCR is a poor
      predictor of CMV end-organ disease.

PMID- 17524194
TI  - Human papillomavirus assay in genital warts--correlation with symptoms.
AB  - Our purpose was to investigate the human papillomavirus (HPV) type distribution
      using the Hybrid Capture 2 (HC2) Microplate assay in males. We tested a urethral
      swab from 550 HIV-negative males with genital warts and 64 HIV-negative males
      clinically free of genital warts, partners of HPV-infected females, using the HC2
      Microplate assay. A perianal swab was also obtained from patients with perianal
      warts. In the first group, HPV DNA of any type was detected in 280 (50.9%)
      patients. Relatively few patients with urethral or perianal warts demonstrated a
      negative test (both P < 0.0001). Low-risk types were commoner, accounting for
      60.0% of the HPV cases, high/intermediate-risk types accounted for 23.6%, while
      46 men (16.4%) were infected with both types. Of 13 subjects (20.3%) of the
      second group who tested positive for HPV DNA, 61.5% were infected by low-risk
      types, 23.1% by high/intermediate-risk types and 15.4% had a dual infection. In
      conclusion, male partners of infected females and males with genital warts are
      predominantly infected by low-risk HPV types, but a substantial proportion is
      also or only affected by high-risk types.

PMID- 17524193
TI  - Sexually transmitted disease symptom management behaviours among female sex
      workers in Tashkent, Uzbekistan.
AB  - The objective of this cross-sectional study was to assess prevalence and
      correlates of self-treatment of sexually transmitted diseases (STD) among female
      sex workers (FSW) in Tashkent, Uzbekistan. Enrolled FSW completed a self
      administered questionnaire, HIV serologic testing and optional pelvic
      examination. STD diagnosis was based on physical examination and/or microscopic
      findings. Of 448 women, 337 (75.0%) accepted examination; of these, 316 (93.8%)
      received at least one STD-related diagnosis. Nearly half (45.4%) reported prior
      STD self-treatment, which was associated with HIV infection (age-adjusted odds
      ratio [AOR] = 3.20, 95% confidence interval [CI] = 1.45-7.53) and condom
      knowledge (AOR = 2.10, 95% CI = 1.16-3.80). For those with history of STD,
      immediate resumption of sex work before completing treatment was common (87.0%).
      STD self-treatment is common among FSW in Tashkent, particularly women with HIV
      infection. Confidential venues for STD care and condom utilization programmes
      targeted to FSW and their clients are needed to prevent STD in this setting.

PMID- 17524195
TI  - B safe, B sorted: results of a hepatitis B vaccination outreach programme.
AB  - The risk of hepatitis B among men having sex with men (MSM) is high, with core
      antibody rates ranging from 5% to 81%. We describe an outreach, hepatitis B
      vaccination programme aiming to raise awareness of hepatitis B and increase
      vaccination uptake. The 13-week programme used an ultra rapid vaccination
      schedule. Follow-up was defined as complete if the client was core antibody
      positive, had adequate surface antibody levels following prior vaccination or
      received three vaccine doses. One hundred and fifty clients were screened for
      hepatitis B and syphilis. Three cases of untreated syphilis (early latent) and
      one case of e-antigen-positive hepatitis B were detected. With the aid of text
      message reminders, a vaccination completion rate of 76.6% was achieved, with
      82.5% completing follow-up. In conclusion, this programme succeeded in reaching
      MSM not routinely accessing services. Text messaging was an acceptable and
      effective method of follow-up, resulting in high vaccination completion rates.

PMID- 17524196
TI  - A comparison of two methods of partner notification for sexually transmitted
      infections in South Africa: patient-delivered partner medication and patient
      based partner referral.
AB  - The objective of this study was to determine acceptability and feasibility of
      patient-based partner referral (PBPR) and patient-delivered partner medication
      (PDPM) among female sexually transmitted infection (STI) patients in a community
      based STI screening study. Women were randomized to STI screening at home or at a
      clinic. STI patients could choose between PBPR and PDPM. Six-week follow-up
      interviews, and in-depth interviews, were conducted. STI prevalence was high.
      Most of the 106 women with an STI chose PDPM, mainly because partners would not
      have time or would not want to attend a clinic, and to ensure that partners
      received treatment. Nearly all partners reportedly took medication (94; 89% took
      it in front of the woman) or went to a clinic for treatment (92%). No adverse
      events were reported. Good communication emerged as the key to successful partner
      notification. In conclusion, PDPM could be used as a strategy to improve STI
      treatment coverage.

PMID- 17524197
TI  - Are we missing mumps epididymo-orchitis?
AB  - Mumps epididymo-orchitis has not been recorded as a cause of testicular symptoms
      without systemic features (including parotitis). The aim of the present study was
      to assess if we were missing cases in the genitourinary clinic during a previous
      outbreak of mumps in the community. During a prospective pilot study from
      November 2005 to February 2006, all patients presenting with symptoms or signs of
      epididymo-orchitis were studied. These patients were assessed for previous
      exposure to mumps virus or vaccine, and any current evidence of systemic illness.
      All patients included had a full sexual health screen (loop test, chlamydia
      polymerase chain reaction [PCR], gonorrhoea culture, HIV and Venereal Disease
      Research Laboratory [test]/Treponema pallidum particle agglutination assay),
      urinary tract infection excluded by urinalysis and mid-stream specimen of urine
      (MSSU) and mumps serology (Immunoglobulin M [IgM] and Immunoglobulin G [IgG])
      performed. Twenty-three patients met inclusion criteria. Their ages ranged from
      16 to 50 years, average 30.8 years. All had symptoms of these, 18 had testicular
      pain, eight swelling, (four had both pain and swelling) and three also had
      dysuria. On examination, 12 had tenderness, seven swelling, (two both tenderness
      and swelling) and six had no signs. Seventeen denied history of mumps, one
      patient had a record of vaccination and five described fever. None had parotid
      swelling. Three patients were chlamydia PCR positive, two had candida cultured,
      three had non-specific urethritis (>10 polymorphonuclear leucocyte/high powered
      field) and 13 had negative sexually transmitted infection screen (one known HIV
      positive). Three had positive IgM mumps serology and two were IgG-positive. It is
      important to include mumps in the differential of epididymo-orchitis and to be
      aware of outbreaks in the community that may present with genital symptoms, as
      the management and partner notification will be different.

PMID- 17524198
TI  - Discontinuation of non-nucleoside reverse transcriptase inhibitor-based highly
      active antiretroviral therapy due to nucleoside analogue reverse transcriptase
      inhibitor-related metabolic toxicity.
AB  - We aimed to evaluate the reasons for, and timing of, treatment changes in a
      cohort of treatment-naive patients initiating non-nucleoside reverse
      transcriptase inhibitor (NNRTI)-containing highly active antiretroviral therapy
      (HAART). All 268 patients initiating these regimens between January 1998 and
      September 2003 were included. Median follow up was 103 weeks. The median baseline
      CD4 count was 150 cells/microL. Seven patients (3%) died and 155 patients (58%)
      experienced a change in their HAART regimen. The reasons drugs were discontinued
      included toxicity in 106 patients (40%), virological failure in 21 (8%), other
      reasons in 23 (9%) and unknown reasons in five (2%). Fifty-one patients (19%)
      stopped NRTIs due to peripheral neuropathy, hyperlactataemia, lipoatrophy,
      lipodystrophy or myelosuppression, and these events were more likely in patients
      with baseline CD4 count below the median (P = 0.039). The findings in this cohort
      show that discontinuation of HAART was commonly due to toxicity, especially
      metabolic or mitochondrial toxicity in those with lower baseline CD4 count.

PMID- 17524199
TI  - An audit of the results of the Roche Amplicor gonorrhoea test on female genital
      samples--a cheaper and more sensitive method than culture in an urban English
      population.
AB  - We report an audit of the use of the Roche Amplicor gonorrhoea test in an urban
      English genitourinary (GU) medicine clinic. A number of studies have shown
      polymerase chain reaction (PCR) to be more sensitive than culture in detecting
      Neisseria gonorrhoea (NG) in genital samples. PCR also offers benefits over
      culture in terms of samples transport and storage requirements but cannot produce
      antibiotic sensitivities. In this audit, the use of both methods within an
      algorithm has reduced the overall cost of NG detection by approximately 30%. In
      all, 4.2% (99 out of 2336) of the endocervical samples were positive, but only
      69% (68 out of 99) of these were also positive by culture. Urine samples showed
      twice as many inhibitory results as positive results: 19 (3%) inhibitory and 10
      (1.5%) positive out of 662 samples. The use of the GC PCR in this protocol has
      been cost-saving and has increased the sensitivity of GC detection, but some
      results have been difficult to interpret. We hope to remedy this by the
      introduction of confirmatory testing for discrepant PCR results.

PMID- 17524200
TI  - Audit of Postal Test Kits in Edinburgh for Chlamydia trachomatis as an
      alternative to genitourinary medicine clinic attendance.
AB  - Our objective was to investigate whether Postal Test Kits (PTKs) for Chlamydia
      trachomatis in Edinburgh offer an alternative to genitourinary (GU) medicine
      clinic attendance. All PTKs returned in the Edinburgh area over a six-month
      period from August 2005 were audited. Data on age and previous access to GU
      medicine services were collected. Return rates of kits from various sources were
      calculated. In all, 799 kits were returned with 72 (9%) chlamydia prevalence, and
      10% had previously attended a GU medicine clinic. The largest proportion of kits
      were used by the 16-29 years old age group. Return rates of kits varied with
      distribution point, with only 15% returned from GU medicine. PTKs appear to be
      targeting an appropriate high-risk age group and a population not otherwise
      accessing GU medicine clinics. However, return rates are low and kits do not
      offer an adequate alternative to GU medicine clinics.

PMID- 17524201
TI  - HIV-infected children vaccination coverage and safety in a Western European
      cohort: a retrospective study.
AB  - Since the implementation of highly active antiretroviral therapy in HIV-infected
      children, response to scheduled vaccines may determinate future morbidity and
      mortality. The aims of this study have been to describe the current vaccine
      coverage, vaccine safety and concordance with vaccine recommendations of the 68
      HIV-infected children and adolescents followed up in our Unit. Forty-four percent
      of the children received at least one dose of the oral polio vaccine (OPV). Only
      9.1% needed and received a second set of hepatitis B virus immunization because
      of low vaccine response. Only 14.7% were vaccinated against varicella. Coverages
      of 82.3% and 100% have been reached with the 23-valent and the 7-valent
      pneumococcal vaccines, respectively. Meningococcal conjugated vaccine uptake was
      moderate (80.8%). Influenza annual vaccination coverage was poor: only 22.7% had
      well-documented yearly vaccines. In our experience, vaccine coverage is lower in
      those vaccines administered in primary care centres compared with the
      immunizations given at the hospital. OPV administration did not cause any adverse
      effect in the children or in their families. Vaccine coverage in HIV-infected
      children was suboptimal.

PMID- 17524202
TI  - An audit on the management of gonorrhoea at the Whittall Street Clinic,
      Birmingham, UK.
AB  - The aim of this study was to investigate the compliance of management of
      gonorrhoea with the national recommendations. The method used was a retrospective
      audit on consecutive cases of culturally proven gonorrhoea. In total, 131 men and
      100 women were included. Four men and nine women were not treated with the
      appropriate antibiotic. Seven women had not received any treatment. Only 0.33
      partners for each case of gonorrhoea were contacted. Uptake of HIV testing was
      64%. Treatment failure was recorded among three of 33 patients with test of cure.
      Oro-pharyngeal swabs were obtained in 34% of the patients with a history of oral
      sex. In only three of the nine auditable standards targets were met. In
      conclusion, staff re-training, updated local protocols, routine offer of test of
      cure and methods to improve partner notification were implemented to improve the
      management of gonorrhoea.

PMID- 17524203
TI  - Renal and gastrointestinal amyloidosis in an HIV-infected injection drug user.
AB  - A 30-year-old HIV-infected intravenous drug user presented with sepsis, acute
      renal failure, oedema, proteinuria and iron deficiency anaemia. After extensive
      investigation, a diagnosis of reactive systemic AA (amyloid, serum amyloid A
      protein) amyloidosis was made on the basis of renal, gastric and duodenal
      biopsies.

PMID- 17524204
TI  - Response to Gisselquist and Correa's article regarding heterosexual commercial
      sex and India's HIV epidemic.

PMID- 17524206
TI  - Tattooing and risk of transmitting HIV in Quthing prison, Lesotho.

PMID- 17524207
TI  - Acceptability of a penile wipe to promote male genital hygiene.

PMID- 17524208
TI  - Under what circumstances do patients with schizophrenia jump to conclusions? A
      liberal acceptance account.
AB  - BACKGROUND: A consistent body of studies suggests that schizophrenia patients are
      extremely hasty when making decisions, and generally opt for the strongest
      response alternative. This pattern of results is primarily based on studies
      conducted with the beads task, which requires participants to determine from
      which of two possible jars a series of beads has been drawn. We have recently
      proposed a liberal acceptance (LA) bias to account for decision-making biases in
      schizophrenia, which claims that under heightened ambiguity the jump to
      conclusions (JTC) bias is abolished in schizophrenia. METHODS: A total of 37
      schizophrenia patients were compared with 37 healthy controls on different
      versions of the beads paradigm. For the first task, participants were required to
      rate the probability that a bead was being drawn from one of two jars, and had to
      evaluate after each bead whether the amount of presented information would
      justify a decision. The second task was a classical draws to decision experiment
      with two jars. The third task confronted participants with four possible jars. If
      JTC was ubiquitous in schizophrenia hasty convergence on one alternative would be
      predicted for all three tasks. In contrast, the LA account predicts an
      abolishment of the JTC effect in the final task. RESULTS: Tasks 1 and 2 provide
      further evidence for the well-replicated JTC pattern in schizophrenia patients.
      In accordance with the LA hypothesis, no group differences were detected for task
      3. DISCUSSION: The present results confirm that JTC is not ubiquitous in
      schizophrenia: in line with the LA account a JTC bias in schizophrenia occurred
      under low but not high ambiguity. LA may partly explain the emergence of fixed,
      false beliefs.

PMID- 17524209
TI  - Illness perception and its relationship to readiness to change in the eating
      disorders: a preliminary investigation.
AB  - OBJECTIVE: This study investigated the psychometric properties of a modified
      version of the Illness Perception Questionnaire - Revised (IPQ-R) in individuals
      with eating disorders. The relationship between illness representations and stage
      of change was then explored. Design and method. A cross-sectional design was
      employed and participants were asked to complete a set of questionnaires. A
      subset of participants completed the IPQ-R again after 2 weeks in order to assess
      test-retest reliability. The relationship between illness representations and
      stage of change was explored using hierarchical multiple regression analyses.
      RESULTS: Sixty-nine participants with a clinical eating disorder took part in the
      study. With the exception of the causal subscales, the modified version of the
      IPQ-R had good internal validity and good test-retest reliability. Consequences,
      treatment control and personal control as well as cyclical timeline perceptions
      accounted for a significant and unique amount of variance in readiness to change
      stage scores. CONCLUSIONS: Findings suggest that this modified version of the IPQ
      R provides a reliable means of exploring illness representations in individuals
      with eating disorders. Given the significant relationships between illness
      representations and stage of change, it may be helpful to consider these aspects
      of illness representations when carrying out therapeutic work with this clinical
      population. Further research might usefully investigate the relationship between
      illness perceptions and clinical outcome, as well as examine what factors are
      important in the shift between stages of change in a longitudinal design.

PMID- 17524210
TI  - Prospects for a cognitive-developmental account of psychotic experiences.
AB  - PURPOSE: It has recently been recognized that psychosis represents the end-point
      of abnormal developmental pathways. The neurodevelopmental framework, within
      which this observation has typically been interpreted, has a number of
      limitations, particularly its failure to take account of recent advances in our
      understanding of the psychology of unusual experiences, such as hallucinations
      and delusions. The purpose of the present review is to highlight the advantages
      of considering psychosis within the framework of mainstream developmental
      psychology. The approach we advocate integrates findings from neurodevelopmental
      research with research on typical cognitive and sociocognitive development and
      the psychology of psychotic symptoms. METHOD: We review selected research on the
      developmental precursors of psychosis and on the role of cognitive processes in
      psychotic symptoms, together with relevant literature addressing the development
      of these processes in healthy children. RESULTS: Developmental psychology
      provides clues about the cognitive and sociocognitive abnormalities that may be
      involved in hallucinations and delusions. An integration of these findings with
      existing knowledge on the neurodevelopment of psychosis suggests new avenues of
      research for investigators working at both biological and psychological levels of
      explanation. CONCLUSIONS: The literature on typical cognitive and sociocognitive
      development provides a rich source of hypotheses about the ontogenetic pathways
      leading to psychosis.

PMID- 17524211
TI  - Specificity of autobiographical memory in depressed older adults and its
      relationship with working memory and IQ.
AB  - OBJECTIVES: The study investigated whether depressed older adults retrieve fewer
      specific memories and more categoric memories than non-depressed older adults on
      the autobiographical memory test (AMT). The second objective was to investigate
      the relationship between AMT performance and both working memory and intelligence
      quotient (IQ). DESIGN: The study was cross-sectional, involving a single
      interview with each participant. METHODS: A group of 17 depressed participants
      was matched for age, gender and education with a group of 17 non-depressed
      participants. All were screened for cognitive impairment. Participants completed
      the AMT, spatial span and letter-number sequencing subtests of the Wechsler
      Memory Scale III and the Wechsler Test of Adult Reading. RESULTS: The depressed
      group retrieved significantly fewer specific memories than the non-depressed
      group, but did not differ in their categoric memory recall. Specific memory
      scores were positively correlated with measures of working memory, but not with
      IQ. Categoric memory scores were negatively correlated with measures of working
      memory, but not with IQ. CONCLUSIONS: Depression adversely affects older adults'
      ability to retrieve specific memories. Working memory capacity was related to
      specific autobiographical memory retrieval independently of IQ. A strong
      relationship between AMT performance and spatial span is discussed.

PMID- 17524212
TI  - The psychological consequences of combat exposure: the importance of appraisals
      and post-traumatic stress disorder symptomatology in the occurrence of delusional
      like ideas.
AB  - OBJECTIVE: The aim of the current study is to explore the association between
      combat experience and the occurrence of delusional-like beliefs. It is
      hypothesized that negative post-trauma appraisals and positive beliefs about
      paranoia will be associated with vulnerability to delusional ideas and that
      veterans who meet criteria for post-traumatic stress disorder (PTSD) will be more
      likely to hold delusional-like ideas. DESIGN: A small-scale survey design was
      employed in order to ensure that detailed information was gathered concerning
      battle exposure. METHODS: Forty-one British war veterans completed questionnaires
      relating to combat experience, delusional ideation, beliefs about paranoia,
      appraisals of combat trauma and PTSD symptomatology. RESULTS: Negative post
      trauma cognitions and positive and negative beliefs about paranoia were
      associated with increased predisposition to delusional beliefs; however, the
      severity of combat experience was not. It was also found that veterans who met
      criteria for PTSD were more likely to hold delusional-like ideas compared with
      those who did not. Furthermore, the PTSD group held more negative post-trauma
      cognitions and more positive beliefs about paranoia. CONCLUSIONS: These findings
      suggest that PTSD symptoms may confer vulnerability to delusional beliefs and
      that this may be mediated by negative appraisals about the self, the world and
      dysfunctional beliefs about paranoia. However, it is possible that psychotic-like
      phenomena confer vulnerability to PTSD. The implications of these findings are
      discussed.

PMID- 17524213
TI  - The role of maladaptive appraisals in child acute stress reactions.
AB  - OBJECTIVE: To test the prediction of cognitive models of trauma that negative,
      catastrophic appraisals central to the development of psychopathological stress
      reactions. DESIGN: A cross-sectional, concurrent design was used. METHODS: Sixty
      six children (aged 7-13 years), who were hospitalized after traumatic injury were
      assessed within 4 weeks of their trauma for acute stress disorder, depression,
      and administered the Child Post-traumatic Cognitions Inventory (cPTCI). Parental
      acute stress was also assessed. RESULTS: Children's negative appraisals of their
      ongoing vulnerability accounted for 44% of the variance of acute stress reactions
      in children. Injury severity, depression, age, and parental acute stress levels
      did not account for significant additional variance. CONCLUSIONS: The findings
      provide support for cognitive models of trauma adaptation and highlight the
      importance of assessing children's appraisals of their traumatic experience in
      order to develop effective interventions.

PMID- 17524214
TI  - Delivering group psychoeducational CBT in Primary Care: comparing outcomes with
      individual CBT and individual psychodynamic-interpersonal psychotherapy.
AB  - Within psychological services in Primary Care, service providers are expected and
      required to deliver clinical services that are prompt, safe and effective.
      However, long wait-times for treatment are common, with attendant clinical
      chronicity and risk issues. Evaluations of group-based treatments in Primary
      Care, which are clinically more efficient than individual treatments, are
      extremely scarce. The current evaluation attempted to appraise the effectiveness
      of a service innovation of introducing group-based psychoeducational cognitive
      behaviour therapy (CBT; N=43), by comparing outcomes with clients treated in
      individual CBT (N=68) and individual psychodynamic-interpersonal psychotherapy
      (N=65). Group psychoeducational participants completed validated scales of
      psychological functioning (Beck Depression Inventory - 2, BDI-2; Brief Symptom
      Inventory, BSI; Inventory of Interpersonal Problems, IIP-32; and General Health
      Questionnaire, GHQ-12) at assessment, start of group, termination of group and 3
      month follow-up, whereas participants in the individual therapies completed
      measures only at initiation and termination of treatment. The results indicate
      broad similarities between the outcomes achieved by the three services, with
      rates of clinically significant improvements and deteriorations comparable in the
      main across services. The results are discussed in terms of identified
      methodological limitations, service implications and models of service delivery
      for the psychological therapies in Primary Care.

PMID- 17524215
TI  - The utility of the recognition memory test and the graded naming test for
      monitoring neurological patients.
AB  - OBJECTIVES: Repeated neuropsychological assessments are often used to monitor
      cognitive changes in neurological patients. In this study we document: test
      retest reliability (TRR), group changes in performance and measures of intra
      subject variability for two commonly used cognitive tests. DESIGN: A large sample
      of neurological patients with either acute or degenerative neurological damage,
      and relatively static cognitive profiles, were retrospectively selected if they
      had been administered twice either the Recognition Memory Test (RMT) and/or the
      Graded Naming Test (GNT) within a 2-year interval. RESULTS: Overall, the TRR of
      the RMT was reasonable in both patient groups, although slightly better in the
      neurodegenerative population. The GNT had excellent reliability in both patient
      populations. For both tests, the intra-subject variability was generally large
      and greater than that observed in healthy adults. CONCLUSIONS: Despite its
      reasonable TRR, the RMT's very large intra-subject variability makes it
      unsuitable for monitoring the gradual changes in episodic memory performance that
      may be associated with both acute and degenerative neurological conditions. In
      contrast, the GNT is a reliable test of nominal skills and is sensitive to
      gradual changes in performance over time.

PMID- 17524216
TI  - Distinguishing between anxiety and depression using the Mood and Anxiety Symptoms
      Questionnaire (MASQ).
AB  - OBJECTIVE: To examine the discriminant validity of the Mood and Anxiety Symptom
      Questionnaire (MASQ) in a sample of young help-seekers. METHOD: 136 young people
      referred to a psychiatric service completed a diagnostic interview and the MASQ.
      RESULTS: Participants were classified according to diagnostic status: Mood Only;
      Anxiety Only; Mixed Anxiety-Depression; Other DSM-IV Disorder; and No Axis-I
      Disorder. Participants in the Mood Only and Mixed groups scored significantly
      higher than the remaining groups on all MASQ scales. Participants in the Anxiety
      Only group did not score significantly higher than participants in the Other DSM
      IV or No Diagnosis groups for any scale. CONCLUSION: Our finding supported the
      specificity of the depression-specific scale, however the purported anxiety
      specific scale did not distinguish between those with and those without Anxiety
      disorders. It was hypothesised that in clinical samples, the MASQ may measure
      general psychological distress.

PMID- 17524217
TI  - The figure copy and recall test of the Adult Memory and Information Processing
      Battery: inter-rater reliability.
AB  - OBJECTIVE: Examined inter-rater reliability of the scoring of the Figure Copy and
      Recall subtest of the Adult Memory and Information Processing Battery (AMIPB;
      Coughlan & Hollows, 1985). METHOD: Figure Copy and Recall tests of 56 individuals
      referred for neuropsychological assessment were independently scored by three
      experienced neuropsychologists and the scores correlated. Detailed analysis of
      reasons for scoring discrepancies was carried out. RESULTS: Raters scores were
      highly correlated in relation to both forms of the tests. The major source of
      discrepancy was errors in accuracy. CONCLUSIONS: Results indicate that the AMIPB
      manual instructions are sufficiently detailed to obtain good inter-rater
      reliability when the raters are experienced clinicians. Further research using
      trainees or assistant psychologists is suggested.

PMID- 17524218
TI  - Relationships between the personality beliefs questionnaire and self-rated
      personality disorders.
AB  - OBJECTIVES: To examine relationships between specific dysfunctional beliefs and
      self-reported personality disorder types. DESIGN: Cross-sectional. METHOD: One
      hundred and sixty-four clinical psychology out-patients completed the Personality
      Beliefs Questionnaire (PBQ) and Millon Multiaxial Clinical Inventory-III (MCMI
      III): 155 completed both. Avoidant, dependent, passive-aggressive and schizoid
      PDs, and relevant PBQ subscales were studied. RESULTS: Presence or absence of PD
      was predicted by scores on the index PBQ subscale. CONCLUSIONS: This pattern has
      previously been reported for PDs diagnosed by structured interview only. PBQ
      relationships with passive-aggressive and schizoid PD have not previously been
      reported.

PMID- 17524219
TI  - The hierarchy of work pursuits of public health managers.
AB  - How public health is managed in various settings is an important but under
      examined issue. We examine themes in the management literature, contextualize
      issues facing public health managers and investigate the relative importance
      placed on their various work pursuits using a 14-activity management model
      empirically derived from studies of clinician-managers in hospitals. Ethnographic
      case studies of 10 managers in nine diverse public health settings were
      conducted. The case study accounts of managers' activities were content analysed,
      and substantive words encapsulating their work were categorized using the model.
      Managerial activities of the nine public health managers were ranked according to
      the number of words describing each activity. Kendall's coefficient of
      concordance yielded W = 0.710, P < 0.000, revealing significant similarity
      between the activity patterns of the public health managers. A rank order
      correlation between the activity patterns of the average ranks for the public
      health sample and for the hospital clinician-managers (n = 52) was R = 0.420, P =
      0.131, indicating no significant relationship between relative activity
      priorities of the two groups. Public health managers put less emphasis on
      pursuits associated with structure, hierarchy and education, and more on external
      relations and decision-making. The model of hospital clinician-managers'
      managerial activities is applicable to public health managers while identifying
      differences in the way the two groups manage. The findings suggest that public
      health management work is more managerialist than previously thought.

PMID- 17524220
TI  - Organizational interventions to promote risk management in primary care: the
      experience in Warwickshire, England.
AB  - Primary care organizations are under-represented in research on quality
      improvement and risk management (RM), yet the potential for improving patient
      safety is possibly greater given the extent that clinical judgement is required
      to achieve a service tailored to the individual's personal health and lifestyle.
      This paper examines how a health authority in England promoted interventions to
      improve RM in General Practice that included the practices' own initiatives,
      significant event audit (SEA) and the Medical Defence Union's workshops which
      included SEA. All 75 practices were approached before the programmes and when
      they were finished, eight months later. The practice manager from each practice
      completed an audit of RM activities, from which a RM competence score was
      derived. Up to six staff per practice completed the Learning organization Culture
      Questionnaire (LCQ) at both times. There was evidence of improved competence in
      RM over the period of the study, particularly through a widening breadth of staff
      involved and in formal recording systems. There was little evidence that these
      improvements were mediated by organizational culture. It is argued that future
      interventions should more closely target specific competences (e.g. recording
      systems for adverse events, root cause analysis to understand error generation)
      and enable staff to see tangible personal and organizational benefits for the
      extra effort involved.

PMID- 17524221
TI  - The psychological contract: is the UK National Health Service a model employer?
AB  - The UK National Health Service (NHS) is facing recruitment challenges that mean
      it will need to become an 'employer of choice' if it is to continue to attract
      high-quality employees. This paper reports the findings from a study focusing on
      allied health professional staff (n = 67), aimed at establishing the expectations
      of the NHS inherent in their current psychological contract and to consider
      whether the government's drive to make the NHS a model employer meets those
      expectations. The findings show that the most important aspects of the
      psychological contract were relational and based on the investment made in the
      employment relationship by both parties. The employment relationship was one of
      high involvement but also one where transactional contract items, such as pay,
      were still of some importance. Although the degree of employee satisfaction with
      the relational content of the psychological contract was relatively positive,
      there was, nevertheless, a mismatch between levels of importance placed on such
      aspects of the contract and levels of satisfaction, with employees increasingly
      placing greater emphasis on those items the NHS is having the greatest difficulty
      providing. Despite this apparent disparity between employee expectation and the
      fulfilment of those expectations, the overall health of the psychological
      contract was still high.

PMID- 17524222
TI  - Improving operational efficiency in an inner-city emergency department.
AB  - Saving lives in a high-volume, high-acuity inner-city trauma centre demands
      operational excellence. We conducted our research in an emergency department
      where treatment of Acute Coronary Syndrome is a critical operation. Our study
      results in a better understanding of patient flow, analysis of the waiting lines
      and an optimization model for labour cost minimization.

PMID- 17524223
TI  - Providers' responses to global budgeting in Taiwan: what were the initial
      effects?
AB  - Taiwan introduced National Health Insurance in 1995, providing comprehensive
      benefits to all of Taiwan's residents, with full access to providers and low co
      payments. The programme quickly increased national health expenditure. To help
      contain these costs, Taiwan introduced global budgeting in 2000-02. Global
      budgeting may present incentives to hospitals to increase service volume to
      maximize revenue. We evaluated the response of hospitals to global budgeting by
      examining hospitalization for selected high-volume discretionary conditions,
      using National Health Insurance data from before and after the implementation of
      global budgeting. Hospitalization for these discretionary conditions increased
      significantly for children, adults of working age, and for some age groups of
      older adults. As there is no reason to believe that hospitalizations would have
      increased during the study period to fulfil unmet need, or as a function of
      either reduced outpatient access or notable increases in disease prevalence,
      results suggest that hospitals increased service volume to retain or expand their
      individual shares of the global budget. The increase in hospitalization for high
      discretion conditions that we observed in this study may not be desirable, as
      hospitalization carries a substantial risk of iatrogenic morbidity, a risk that
      is particularly great for older people.

PMID- 17524224
TI  - Quality improvement with the new general practitioner contract - myth or reality?
AB  - The introduction of the new general practitioner (GP) contract has been a
      significant development in the management of primary care and requires a number
      of changes to be made to the way things are done. This paper provides an initial
      evaluation of the impacts of the new contract from the perspective of practising
      GPs in the Greater Glasgow area of Scotland. Its impact is assessed using
      Ovretveit's three dimensions of quality: professional, client and managerial
      quality. Some of the changes have proved so far to have positive effects and some
      may prove to be increasingly negative if appropriate amendments to the contract
      are not realized. There are some noteworthy implications for policy here.

PMID- 17524225
TI  - Impact of open-access scheduling on realized access.
AB  - Open-access or advanced-access scheduling, which opens the clinic calendar to
      patients without requiring them to schedule far in advance of the visit, is being
      introduced in primary care for the purpose of improving access. None of the
      evaluations reported to date have measured differences in actual visits that
      might be associated with different scheduling systems. The purpose of this study
      was to compare utilization of visits to primary care providers for patients
      served by an open-access clinic with utilization patterns of patients served at
      clinics not using open-access scheduling. We hypothesized that the odds that a
      continuing patient received more than one primary care visit would be greater in
      the clinic where open-access scheduling was in use than in comparison clinics.
      Our study provides mixed support for the hypotheses. After adjustment for case
      mix, stable chronic patients treated in open-access clinics may sometimes have
      greater odds of receiving two or more preventive care visits. However, these
      effects do not occur in all clinics, suggesting that other clinic characteristics
      may overcome the effects of open-access scheduling.

PMID- 17524226
TI  - The use of proteomics to identify novel therapeutic targets for the treatment of
      disease.
AB  - The completion of the Human Genome Project has revealed a multitude of potential
      avenues for the identification of therapeutic targets. Extensive sequence
      information enables the identification of novel genes but does not facilitate a
      thorough understanding of how changes in gene expression control the molecular
      mechanisms underlying the development and regulation of a cell or the progression
      of disease. Proteomics encompasses the study of proteins expressed by a
      population of cells, and evaluates changes in protein expression, post
      translational modifications, protein interactions, protein structure and splice
      variants, all of which are imperative for a complete understanding of protein
      function within the cell. From the outset, proteomics has been used to compare
      the protein profiles of cells in healthy and diseased states and as such can be
      used to identify proteins associated with disease development and progression.
      These candidate proteins might provide novel targets for new therapeutic agents
      or aid the development of assays for disease biomarkers. This review provides an
      overview of the current proteomic techniques available and focuses on their
      application in the search for novel therapeutic targets for the treatment of
      disease.

PMID- 17524227
TI  - Cyclodextrin microparticles for drug delivery to the posterior segment of the
      eye: aqueous dexamethasone eye drops.
AB  - Delivery of steroids to the retina is currently undertaken with invasive
      injections into the vitreous cavity. This paper describes a non-invasive method
      to deliver steroids in therapeutic levels to the retina in rabbits. Dexamethasone
      was formulated as somewhat water-soluble dexamethasone/gamma-cyclodextrin
      (gammaCD) microparticles in a low-viscosity aqueous eye drop suspension. The mean
      (+/-standard deviation) diameter of the particles was 20.4+/-10.3 microm, with no
      particles larger than 60 microm. The aqueous suspension formulation was tested in
      rabbits and compared with an aqueous dexamethasone eye drop solution containing
      randomly methylated beta-cyclodextrin (RMbetaCD). The dexamethasone concentration
      was identical in both formulations (15 mg mL(-1)). The drug was administered to
      the left eye but determined in both eyes. The amount reaching different eye
      tissues via the topical route was determined by subtracting the amount found in
      the right eye from the amount found in the left eye. Two hours after single
      application of the dexamethasone/gammaCD eye drops to rabbits the mean (+/-s.d.)
      concentration in vitreous was 29+/-16 ng g(-1), 86% of which reached vitreous via
      the topical route and in retina the concentration was 57+/-22 ng g(-1) (49% via
      topical route). For the RMbetaCD the values were 22.6+/-9 and 66+/-49 ng g(-1)
      (73 and 14% via topical route), respectively. These steroid levels are comparable
      with the dexamethasone concentration achieved 1 month after intravitreal
      injection. The aqueous dexamethasone/gammaCD eye drop formulation was chemically
      stable during 7 months storage and well tolerated with no visible short-term side
      effects.

PMID- 17524228
TI  - Analysis of eupatilin-human serum albumin interactions by means of spectroscopic
      and computational modelling.
AB  - The interaction of eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) with human
      serum albumin (HSA) was studied at simulative physiological pH, with a HSA
      concentration of 3.0 x 10(-6)mol L(-1) and eupatilin concentrations over the
      range of 6.0 x 10(-6) to 1.9 x 10(-5) mol L(-1). Fluorescence spectroscopy in
      combination with UV absorption spectroscopy and Fourier transform infrared (FTIR)
      spectroscopy were used to study the binding properties (including binding
      mechanism, the binding constants, the number of binding sites and the binding
      mode) of the interaction of eupatilin with HSA and the effect of this drug on HSA
      conformation changes. According to the Scatchard equation there was only one
      class of binding site that could bind to HAS; the binding constants were 1.53 x
      10(5), 1.20 x 10(5), 1.05 x 10(5), 0.87 x 10(5) L mol(-1) at temperatures of 287,
      298, 310 and 318 K, respectively. The FTIR spectra revealed that the protein
      secondary structure changed, with reductions in alpha-helices of about 3.65% at a
      drug to protein molar ratio of 3. The thermodynamic analysis (enthalpy and
      entropy change: DeltaH(0) and DeltaS(0)) and the computational modelling study
      indicated that hydrophobic force played an important role in eupatilin-HSA
      complex stabilization, and eupatilin could bind within the subdomain IIA of HSA.

PMID- 17524229
TI  - Physicochemical characterization of solid dispersions of three antiepileptic
      drugs prepared by solvent evaporation method.
AB  - We have investigated the solid dispersion and dissolution profiles of three
      antiepileptic drugs (carbamazepine (CBZ), oxcarbazepine (OXC) and rufinamide
      (RFN)) with different aqueous solubilities, prepared by the solvent evaporation
      method. Solid dispersions of the three drugs in hydroxy-propylmethylcellulose
      (HPMC), with drug:polymer ratios of 1:4, were prepared and characterized by
      differential scanning calorimetry (DSC), Fourier transformation infrared (FTIR)
      spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy. The
      release mechanism was also investigated and the kinetic order of the solid
      dispersions was evaluated. It appeared that the dissolution behaviour depended on
      the physicochemical properties of the drug and drug-polymer interactions. DSC
      thermographs showed amorphous forms for all drugs confirmed by XRD patterns. The
      FTIR spectra of CBZ and OXC demonstrated drug interactions with HPMC through
      hydrogen polymer bonds. Thus, solid dispersions of these drugs had an improved
      dissolution profile. In contrast, solid dispersions of RUF showed modest
      enhancement of dissolution, suggesting negligible drug-polymer interactions. The
      different dissolution behaviour is attributed to the extent of interactions
      between the polymer hydroxyl group and the drug amide groups.

PMID- 17524230
TI  - Transport characteristics of zolmitriptan in a human intestinal epithelial cell
      line Caco-2.
AB  - The intestinal absorption characteristics and the efflux mechanisms of
      zolmitriptan, a new generation and highly selective 5-HT(1B/1D) receptor agonist
      used in the acute oral treatment of migraine, were investigated. A human
      intestinal cell line, Caco-2, was used as an in-vitro model of the intestinal
      mucosa to assess transepithelial transport of zolmitriptan. In the Caco-2 cells,
      the absorptive transport of zolmitriptan was pH dependent and the transport was
      enhanced at weakly alkali pH on the apical side. No concentration dependence and
      saturation were observed for the apical-to-basolateral and basolateral-to-apical
      transport of zolmitriptan at a concentration of 0.1-10 mM. The permeability ratio
      value was about 1.5-2.6 at a concentration of 0.1-2.0 mM. Inhibition experiments
      using verapamil, nifedipine and nimodipine as inhibitors were studied and
      indicated that P-glycoprotein participated in the transport of zolmitriptan.
      Inhibition of the Na+-H+ exchanger with amiloride resulted in a significant
      increase in absorption and a slight inhibition in secretion. This suggests that
      the Na+-H+ exchanger may be involved in the transport of zolmitriptan. The
      results indicated that the transport of zolmitriptan was mediated by both passive
      diffusion and active transport. A series of drug-drug interaction experiments
      were carried out between zolmitriptan and some drugs that may be co-administrated
      with zolmitriptan in the clinic. The results indicated that flunarizine,
      cetirizine, propranolol and atenolol potently decreased both the apical-to
      basolateral and basolateral-to-apical transport rate of zolmitriptan. Cimetidine
      and aspirin slightly inhibited the apical-to-basolateral transport of
      zolmitriptan, but significantly decreased the basolateral-to-apical transport of
      zolmitriptan. Thus, the absorption drug-drug interactions should be considered
      when these drugs are co-administrated with zolmitriptan in the clinic.

PMID- 17524231
TI  - Preparation, characterization and pharmacokinetics of N-palmitoyl chitosan
      anchored docetaxel liposomes.
AB  - The objective of this work was to investigate the preparation, characterization
      and pharmacokinetics of N-palmitoyl chitosan anchored docetaxel liposomes. To
      decrease toxic effects and improve antitumour efficacy of the drug, docetaxel has
      been incorporated in liposomes; the formulation, stability and pharmacokinetics
      of plain docetaxel liposomes (PDLs), PEGylated docetaxel liposomes (PEGDLs) and N
      palmitoyl chitosan anchored docetaxel liposomes (NDLs) were compared. NDL was
      more stable than PDL and PEGDL in-vitro, especially in the presence of serum at
      37 degrees C. The concentration of docetaxel in the plasma of rats after
      intravenous administration of docetaxel injection, PDL, PEGDL and NDL was studied
      by RP-HPLC. The pharmacokinetic behaviour of docetaxel injection, PDL, PEGDL and
      NDL were significantly different. These findings suggest that anchored liposomes
      could increase the stability of docetaxel in-vivo, as compared with plain
      liposomes, but the improvement was not more significant than PEGylated liposomes.
      N-Palmitoyl chitosan as a new polymeric membrane to anchor liposome was useful to
      stabilize liposomes containing anti-tumour drug.

PMID- 17524232
TI  - Synthesis and pharmacological investigation of novel 3-(3-methylphenyl)-2
      substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents.
AB  - A variety of novel 3-(3-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones
      were synthesized by reacting the amino group of 2-hydrazino-3-(3-methylphenyl)-3H
      quinazolin-4-one with a variety of aldehydes and ketones. The starting material 2
      hydrazino-3-(3-methylphenyl)-3H-quinazolin-4-one was synthesized from 3-methyl
      aniline. The title compounds were investigated for analgesic, anti-inflammatory
      and ulcerogenic index activities. Compound 2-(1-ethylpropylidene-hydrazino)-3-(3
      methylphenyl)-3H-quinazolin-4-one (AS2) was the most active analgesic agent.
      Compound 2-(1-methylbutylidene-hydrazino)-3-(3-methylphenyl)-3H-quinazolin-4-one
      (AS3) was the most active anti-inflammatory agent and was moderately more potent
      than the reference standard diclofenac sodium. The test compounds showed only
      mild ulcerogenic potential compared with aspirin.

PMID- 17524233
TI  - Inhibition of intermediate-conductance Ca2+-activated K+ channel and
      cytoprotective properties of 4-piperidinomethyl-2-isopropyl-5-methylphenol.
AB  - The ionic mechanisms and cytoprotective activities of 4-piperidinomethyl-2
      isopropyl-5-methylphenol (THPI), an analogue of thymol, were investigated in HL
      60 granulocytes and in human erythrocytes, respectively. THPI inhibited K+
      outward current (I(K)) in a concentration-dependent manner in HL-60 leukocytes,
      with an IC50 value of 4 microM. Neither iberiotoxin (200 nM) nor paxilline (1
      microM) suppressed the amplitude of I(K), whereas clotrimazole (5 microM)
      significantly inhibited it. In the inside-out configuration of single channel
      recordings, application of THPI (5 microM) into the bath medium did not alter the
      single-channel conductance of intermediate-conductance Ca2+-activated K+ (IK(Ca))
      channels (i.e K(Ca)3.1 channels), but it suppressed the channel activity
      significantly. THPI-induced inhibition of IK(Ca) channels was reversed by a
      further application of 1-ethyl-2-benzimidazolinone (10 microM). THPI-induced
      reduction in IK(Ca)-channel activity in these cells was primarily due to a
      decrease in mean open time. These results provide direct evidence that THPI is
      capable of suppressing the activity of IK(Ca) channels in HL-60 cells. The
      antioxidant action of THPI also revealed a beneficial cytoprotective effect
      against mitomycin C-mediated haemolytic effect in human erythrocytes. The results
      of this study suggest that blockade of IK(Ca) channels and the membrane
      protecting activity of THPI would combine to have beneficial effects in lessening
      the severity of haemolytic crisis and reducing anaemia in sickle cell disease.

PMID- 17524234
TI  - Protective effect of Chinese prescription Kangen-karyu and its crude drug Tanjin
      against age-related lipidosis in rats.
AB  - We have investigated the effect of the Chinese prescription Kangen-karyu and its
      crude drug Tanjin against age-related lipidosis in-vivo in a rat model. The serum
      and hepatic triglyceride levels were remarkably elevated in 12-month-old compared
      with two-month-old rats. However, the administration of Kangen-karyu and Tanjin
      extracts significantly decreased these levels. This suggested a protective role
      against related pathological conditions as well as hyperlipidaemia. On the other
      hand, the reduction of the levels of adiponectin in serum with ageing did not
      show significant changes in rats given diets supplemented with Kangen-karyu and
      Tanjin extracts. Furthermore, the expression of transcription factors in nuclear
      hepatic tissue related to lipid metabolism was investigated. The decline in the
      expression of nuclear peroxisome proliferator-activated receptor alpha protein in
      hepatic tissue with age was ameliorated by the administration of Kangen-karyu and
      Tanjin supplements. On the other hand, the overexpression of sterol regulatory
      element-binding proteins (SREBP)-1 and SREBP-2 in old rats compared with young
      rats showed a tendency to decrease with Kangen-karyu and Tanjin administration.
      The decline of hepatic function with ageing was attenuated by Kangen-karyu and
      Tanjin, suggesting the beneficial role of Kangen-karyu and Tanjin on lipid
      metabolism through the improvement of hepatic function. This study has
      demonstrated that Kangen-karyu and Tanjin inhibited the accumulation of
      triglyceride with regulation of related protein expressions and they improved
      hepatic function. Evidence has been provided for the anti-ageing activity of
      Kangen-karyu and its crude drug Tanjin against age-related lipidosis.

PMID- 17524235
TI  - Beneficial effects of the extract from Corydalis yanhusuo in rats with heart
      failure following myocardial infarction.
AB  - As indicated in ancient Chinese medical books, Corydalis yanhusuo has therapeutic
      effects on cardiovascular diseases. The analgesic effect of this plant has been
      fully elucidated, and l-tetrahydropalmatine has been shown to be the main active
      principle. The aim of this investigation was to evaluate its protective effects
      in a rat heart failure model. Rats were subjected to coronary artery ligation,
      and orally administered with ethanolic extract of Corydalis yanhusuo 50, 100, or
      200 mg kg(-1) daily, from the 7th day after surgery. We measured cardiac
      function, plasma atrial natriuretic peptide (ANP), relative heart and lung
      weights, infarct size and ventricular dilatation after treatment for 8 weeks.
      Administration with Corydalis yanhusuo led to a significant reduction in infarct
      size and improvement in cardiac function as demonstrated by lower left
      ventricular end diastolic pressure (LVEDP) and elevated +/-dp/dt(max). We also
      found that Corydalis yanhusuo significantly reduced left ventricular (LV)/body
      weight ratio, lung/body weight ratio and significantly inhibited neurohormonal
      activation. Taken together, this study indicated that Corydalis yanhusuo exerted
      salutary effects on heart failure induced by myocardial infarction in rats.

PMID- 17524236
TI  - Topical anti-inflammatory activity of extracts and compounds from Hypericum
      perforatum L.
AB  - Three preparations of Hypericum perforatum L. (a hydroalcoholic extract, a
      lipophilic extract and an ethylacetic fraction) and the pure compounds hypericin,
      adhyperforin, amentoflavone, hyperoside, isoquercitrin, hyperforin
      dicyclohexylammonium (DHCA) salt and dicyclohexylamine were evaluated for their
      topical anti-inflammatory activity. H. perforatum preparations provoked a dose
      dependent reduction of Croton-oil-induced ear oedema in mice, showing the
      following rank order of activity: lipophilic extract > ethylacetic fraction >
      hydroalcoholic extract (ID50 (dose that inhibited oedema by 50%) 220, 267 and
      >1000 microg cm(-2), respectively). Amentoflavone (ID50 0.16 micromol cm(-2)),
      hypericin (ID50 0.25 micromol cm(-2)), hyperforin DHCA salt (ID50 0.25 micromol
      cm(-2)) and adhyperofrin (ID50 0.30 micromol cm(-2)) had anti-inflammatory
      activity that was more potent or comparable to that of indometacin (ID50 0.26
      micromol cm(-2)), whereas isoquercitrin and hyperoside were less active (ID50
      about 1 micromol cm(-2)). As dicyclohexylamine alone was inactive, the effect of
      hyperforin DHCA salt can be attributed completely to the phloroglucinol moiety.
      The pharmacological activity and phytochemical profile of the tested extracts and
      fraction suggest that different constituents are involved in the topical
      antiphlogistic property of H. perforatum in-vivo.

PMID- 17524237
TI  - An ethanol extract of Piper betle Linn. mediates its anti-inflammatory activity
      via down-regulation of nitric oxide.
AB  - The leaves of Piper betle (locally known as Paan) have long been in use in the
      Indian indigenous system of medicine for the relief of pain; however, the
      underlying molecular mechanisms of this effect have not been elucidated. The anti
      inflammatory and immunomodulatory effects of an ethanolic extract of the leaves
      of P. betle (100 mg kg(-1); PB) were demonstrated in a complete Freund's adjuvant
      induced model of arthritis in rats with dexamethasone (0.1 mg kg(-1)) as the
      positive control. At non-toxic concentrations of PB (5-25 microg mL(-1)), a dose
      dependent decrease in extracellular production of nitric oxide in murine
      peritoneal macrophages was measured by the Griess assay and corroborated by flow
      cytometry using the nitric oxide specific probe, 4,5-diaminofluorescein-2
      diacetate. This decreased generation of reactive nitrogen species was mediated by
      PB progressively down-regulating transcription of inducible nitric oxide synthase
      in macrophages, and concomitantly causing a dose-dependent decrease in the
      expression of interleukin-12 p40, indicating the ability of PB to down-regulate T
      helper 1 pro-inflammatory responses. Taken together, the anti-inflammatory and
      anti-arthrotic activity of PB is attributable to its ability to down-regulate the
      generation of reactive nitrogen species, thus meriting further pharmacological
      investigation.

PMID- 17524238
TI  - Antiproliferative, cytotoxic and antitumour activity of coumarins isolated from
      Calophyllum brasiliense.
AB  - Among the eight Calophyllum species found on the American continent, Calophyllum
      brasiliense is the most widely distributed. Chemical analysis of this species has
      shown the presence of xanthones with cancer chemopreventive properties and
      antifungal activity. Recently, three new coumarins with antineoplastic properties
      have been found. In this study, we have evaluated the biological effects of the
      antiproliferative activity of coumarins isolated from C. brasiliense on the
      survival, cell cycle and apoptosis of cells in-vitro and their antitumour effects
      in mice. The cytological study showed that coumarins from C. brasiliense reduce
      the survival of BMK cells (baby mouse kidney cells) by inducing apoptosis and, to
      a lesser degree, necrosis. The cell cycle was arrested in S-phase and the
      division of BMK cells was inhibited. Coumarins had caused a reduction of
      experimental tumours in 83% of animals by the end of the treatment. Therefore,
      coumarins have the potential to be used alone or in combination with other
      antineoplastic drugs, and they might increase the effectiveness of other
      treatments for cancer.

PMID- 17524239
TI  - Red wine polyphenolic compounds inhibit tracheal smooth muscle contraction during
      allergen-induced hyperreactivity of the airways.
AB  - The aims of the study were to investigate the short and long-term effects of
      Provinol (red wine polyphenolic compounds) on tracheal smooth muscle reactivity
      using an in-vitro model of ovalbumin-induced airway inflammation in guinea-pig
      trachea, and to evaluate the role of nitric oxide (NO) in the bronchodilatory
      effect of Provinol. The amplitude of tracheal smooth muscle contraction in
      response to mediators of bronchoconstriction - histamine (10 nM-1 mM),
      acetylcholine (10 nM-1 mM) and to allergen (ovalbumin 10(-5)-10(-3) g mL(-1)) was
      used as a parameter of tracheal smooth muscle reactivity. To test the short-term
      effects of Provinol, isolated tracheal strips were pre-treated for 30 min with
      Provinol (10(-4) mg mL(-1)) alone or in combination with Nomega-nitro-L-arginine
      methyl ester (L-NAME; 10(-6) mol L(-1)). To test the long-term effects of
      Provinol, isolated tracheal strips were prepared from guinea pigs that had been
      treated for 14 days with Provinol (20 mg kg(-1) per day) alone or in combination
      with L-NAME (40 mg kg(-1) per day). Incubation of tracheal smooth muscle with
      Provinol decreased the amplitude of contraction in response to ovalbumin,
      histamine and acetylcholine. The non-selective NO synthase inhibitor L-NAME
      partially abolished the effect of Provinol on acetylcholine and ovalbumin-induced
      but not histamine-induced bronchoconstriction. A similar profile was observed
      after 14 days' oral administration of Provinol. In conclusion, Provinol inhibited
      the allergen- and spasmogen-induced contraction of tracheal smooth muscle in
      ovalbumin-sensitized guinea pigs via a mechanism that was mediated at least
      partially through the metabolism of NO.

PMID- 17524240
TI  - Differential involvement of TRPV1 receptors at the central and peripheral nerves
      in CFA-induced mechanical and thermal hyperalgesia.
AB  - Transient receptor potential vanilloid 1 (TRPV1) antagonists are known to
      attenuate two typical symptoms of inflammatory hyperalgesia: thermal and
      mechanical. However, it is not clear whether the sites of participation of TRPV1
      for each symptom are different. In this study, we clarified the difference
      between the site of TRPV1 involvement in both symptoms by analysing the anti
      hyperalgesic activity of two kinds of TRPV1 antagonists given locally (i.e.
      intraplantarly and intrathecally) in rats with CFA (complete Freund's adjuvant)
      induced inflammation. TRPV1 antagonists BCTC (N-(4-tertiarybutylphenyl)-4-(3
      cholorphyridin-2-yl) tetrahydropyrazine-1(2H)-carbox-amide, 1-300 microg) and SB
      366791 (N-(3-methoxyphenyl)-4-chlorocinnamide, 30-300 microg) administered
      intraplantarly in a dose-dependent manner inhibited CFA-induced thermal
      hyperalgesia. In addition, CFA-induced thermal hyperalgesia was significantly
      reversed by intrathecal administration of 1-100 microg of BCTC and SB-366791.
      While intraplantar BCTC (1-300 microg) and SB-366791 (30-300 microg) did not
      reverse CFA-induced mechanical hyperalgesia, 1-100 microg of intrathecally
      administered BCTC and SB-366791 dose-dependently reduced mechanical hyperalgesia.
      Regression analysis showed that a correlation exists between the inhibitory
      effects on thermal hyperalgesia and mechanical hyperalgesia after intrathecal
      administration (correlation factor = 0.6521), but not after intraplantar
      administration (correlation factor = 0.0215). These data suggest that TRPV1 in
      the peripheral endings of the primary afferents plays a key role in thermal
      hyperalgesia, but it makes only a minor contribution in CFA-induced mechanical
      hyperalgesia. Furthermore, it is suggested that the spinal TRPV1 is critical in
      the development of both types of hyperalgesia.

PMID- 17524241
TI  - The "double-faced" effect of VC-12 on free-radical-induced haemolysis of human
      erythrocytes: antioxidant and prooxidant.
AB  - Vitamin C is a popular antioxidant; however, its water solubility limits its
      function in the lipid environment. As a result, the antioxidative properties of
      its lipophilic derivatives have aroused research attention, especially L-ascorbyl
      6-laurate (VC-12). We have investigated the effect of a high concentration of VC
      12 on 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced haemolysis of
      human erythrocytes. The findings indicated that VC-12 was capable of protecting
      erythrocytes against AAPH-induced haemolysis when its concentration was below 60
      microM. With an increase in the concentration of VC-12 and a decrease in the
      concentration of AAPH, VC-12 promoted haemolysis remarkably, the mechanism of
      which has been proposed as VC-12-mediated peroxidation. When the concentration of
      VC-12 was increased to above 150 microM, VC-12 promoted haemolysis by its
      function as a surfactant, to unbalance the osmotic pressure within and outside
      erythrocytes. High concentrations of VC-12 may have generated radicals via
      autooxidation, resulting in eventual haemolysis. Therefore, the double-faced
      effect of VC-12 on haemolysis of human erythrocytes was due to its concentration.
      This information may be useful for the safe use of lipophilic vitamin C.

PMID- 17524242
TI  - Generalized regression neural networks in prediction of drug stability.
AB  - This study had two aims. Firstly, we wanted to model the effects of the
      percentage of Eudragit RS PO and compression pressure as the most important
      process and formulation variables on the time course of drug release from
      extended-release matrix aspirin tablets. Secondly, we investigated the
      possibility of predicting drug stability and shelf-life using an artificial
      neural network (ANN). Ten types of matrix aspirin tablets were prepared as model
      formulations and were stored in stability chambers at 60 degrees C, 50 degrees C,
      40 degrees C and 30 degrees C and controlled humidity. Samples were removed at
      predefined time points and analysed for acetylsalicylic acid (ASA) and salicylic
      acid (SA) content using stability-indicating HPLC. The decrease in aspirin
      content followed apparent zero-order kinetics. The amount of Eudragit RS PO and
      compression pressure were selected as causal factors. The apparent zero-order
      rate constants for each temperature were chosen as output variables for the ANN.
      A set of output parameters and causal factors were used as training data for the
      generalized regression neural network (GRNN). For two additional test
      formulations, Arrhenius plots were constructed from the experimentally observed
      and GRNN-predicted results. The slopes of experimentally observed and predicted
      Arrhenius plots were tested for significance using Student's t-test. For test
      formulations, the shelf life (t(95%)) was then calculated from experimentally
      observed values (t(95%) 82.90 weeks), as well as from GRNN-predicted values
      (t(95%) 81.88 weeks). These results demonstrate that GRNN networks can be used to
      predict ASA content and shelf life without stability testing for formulations in
      which the amount of polymer and tablet hardness are within the investigated
      range.

PMID- 17524243
TI  - Effect of artesunate plus sulfadoxine-pyrimethamine on haematological recovery
      and anaemia, in Kenyan children with uncomplicated, Plasmodium falciparum
      malaria.
AB  - Malaria-associated anaemia is a major public-health problem. Although the
      treatment of uncomplicated, Plasmodium falciparum malaria aims to clear the
      parasites, relieve the symptoms and permit haematological recovery, data on the
      impact of antimalarial treatment on haematological recovery are few.
      Haematological recovery and the prevalence of anaemia were therefore evaluated in
      600 Kenyan children with uncomplicated malaria who were randomly assigned to one
      of three treatment groups. The children were given sulfadoxine-pyrimethamine (SP)
      on day 0, SP plus artesunate on day 0 (AS1), or SP on day 0 and artesunate on
      each of days 0-2 (AS3). Haemoglobin (Hb) concentrations were measured on days 0,
      7, 14, 21 and 28, with haematological recovery defined as a day-28 Hb
      concentration of at least 11 g/dl. Only 96 (18%) of the 543 children who were
      anaemic (i.e. with <11.0 g Hb/dl) at enrolment achieved haematological recovery.
      The prevalence of anaemia fell from 91% on day 0 to 74% (252/340) by day 28
      (P=0.065). Compared with SP alone, neither artesunate regimen resulted in higher
      Hb concentrations on day 28 (with means of 10.2, 9.9 and 10.2 g/dl for AS3, AS1
      and SP, respectively; P=0.254), a higher frequency of haematological recovery
      (19%, 14% and 20% for AS3, AS1 and SP, respectively; P=0.301) or a greater
      reduction in the prevalence of anaemia (prevalences in the AS3, AS1 and SP arms
      falling from 90%, 89% and 93%, respectively, on day 0, to corresponding values of
      71%, 82% and 69% on day 28; P=0.40). In fact, between days 0 and 7, the children
      in the AS3 arm showed a larger drop in mean Hb than the children in the other two
      treatment arms. In general, haematological recovery was most likely in older
      children who had mild anaemia at presentation and were parasitologically cured.
      Overall, the frequencies of haematological recovery were modest and not
      influenced by the artesunate treatments. Other factors contributing to anaemia
      need to be explored more fully.

PMID- 17524244
TI  - Ability of mothers to diagnose fever and anaemia in their young children, in a
      malaria-endemic region of West Africa.
AB  - The rapid and correct diagnosis of fever and anaemia at the household level is a
      prerequisite for the successful management and control of life-threatening
      disease among young children, particularly in malaria-endemic areas of Africa.
      The ability of mothers to diagnose fever and anaemia in their young children has
      recently been explored, as part of a large, birth-cohort study in rural, north
      western Burkina Faso. During a cross-sectional survey in six villages, 345
      children aged, <3 years and their mothers were investigated. Each mother was
      asked if she considered her child to be febrile and/or anaemic before that
      child's temperature and haematocrit were measured, with an electronic thermometer
      and portable centrifuge, respectively. The recorded prevalences of fever (> or
      =37.5 degrees C) and anaemia (haematocrit, <25%) in the children were 12.2% and
      21.4%, respectively. The mothers' diagnoses had a sensitivity of 76.2% [95%
      confidence interval (CI)=60.6%-88.0%] for fever and 4.1% (CI=0.8%-11.4%) for
      anaemia, with corresponding specificities of 87.1% (CI=82.8%-90.7%) and 95.9%
      (CI=92.9%-98.0%). Mothers in rural Africa appear to be fairly accurate in
      detecting fever in their children but less accurate in detecting anaemia. While
      malaria control needs to employ a mix of preventive and curative measures,
      anaemia control will benefit from community-based malaria-control measures as
      well as broader approaches addressing the nutritional status of young children.

PMID- 17524245
TI  - Detection of in-vivo chloroquine resistance in Plasmodium falciparum from
      Rameswaram Island, a pilgrim centre in southern India.
AB  - Resistance to chloroquine (CQ) in Plasmodium falciparum is one of the main causes
      of the wide-spread resurgence of malaria in India and a challenge to the
      effective control of the disease. In the pilgrim centre of Rameswaram Island,
      malaria has persisted despite the various control measures undertaken over the
      years. When CQ resistance in Rameswaram was investigated in vivo, recrudescent
      parasitaemias were observed in 25 (58%) of the 43 study subjects who were given
      CQ and completed follow-up, all occurring between days 10 and 28 (late treatment
      failures). The results of the msp(1), msp(2) and glurp genotyping of paired
      samples of P. falciparum, collected on day 0 and the day of recrudescence from 23
      of the apparent treatment failures, indicated that 21 (91%) of the 23 were
      probably true treatment failures. All of the paired samples harboured parasites
      with the K76T mutation in their pfcrt genes, and subsequent sequencing of nine
      day-0 samples revealed the SVMNT haplotype in all nine. This is the first report
      of in-vivo drug resistance in P. falciparum from Rameswaram Island. Such
      resistance, which is probably the result of the indiscriminate use of CQ and/or
      the import of malaria from mainland India, warrants a change in the drug regimen
      used locally for the first-line treatment of uncomplicated, P. falciparum
      malaria, to make treatment more effective and slow the development and spread of
      more foci of CQ resistance.

PMID- 17524246
TI  - A search for the rodent hosts of Leishmania major in the Larestan region of
      southern Iran: demonstration of the parasite in Tatera indica and Gerbillus sp.,
      by microscopy, culture and PCR.
AB  - Zoonotic cutaneous leishmaniasis (CL) caused by Leishmania major occurs widely in
      Iran, where several species of rodent serve as the parasite's 'reservoir' hosts.
      In an attempt to identify the rodent hosts in the Larestan region, which lies in
      the Fars province of southern Iran (where the incidence of human CL has been
      rising), 32 rodents (20 Tatera indica, eight Meriones crassus, four Gerbillus
      sp.) were caught and checked for leishmanial infection. Using two detection
      methods (the microscopical examination of stained tissue smears and the culture
      of tissue samples) and a PCR to identify any leishmanial parasites detected, L.
      major was identified in six of the rodents caught: two male T. indica from
      Alamarvdasht, two female T. indica from Lamerd, and two females of the genus
      Gerbillus (one caught in Lamerd and one in Lar). Although the samples were too
      small to prove that M. crassus is not a significant host of L. major in Larestan,
      they were large enough to indicate that T. indica and members of the genus
      Gerbillus serve as reservoir hosts of L. major in the region. Tatera indica
      appears to be an important host of L. major across much of Iran but this appears
      to be the first time that the genus Gerbillus has been found to be involved in
      the epidemiology of CL in the country.

PMID- 17524247
TI  - Progress towards the elimination of onchocerciasis as a public-health problem in
      Uganda: opportunities, challenges and the way forward.
AB  - The national onchocerciasis-control programme in Uganda successfully eliminated
      Simulium neavei s.s. from the Itwara focus in 1997, by monthly ground spraying
      with larvicidal temophos (Abate). Since then, no vectors have been caught in the
      main Itwara focus or two secondary foci in the same area. After 4 years of
      intervention, S. neavei s.s. has also been nearly eliminated from the Mpamba
      Nkusi focus, and the elimination of this vector from two more foci (West Nile and
      Wambabya-Rwamarongo) appears quite feasible. There are, however, four isolated
      foci in Uganda (Budongo, Kashoya-Kitomi, Mount Elgon and Kigezi-Bwindi) which are
      probably too large and inaccessible to make the elimination of S. neavei s.s. by
      ground spraying a realistic possibility. Encouragingly, >70% of Ugandans have
      received an annual dose of ivermectin for at least 10 years, and the national
      programme of community-directed treatment with ivermectin (CDTI) is thought to be
      progressing towards sustainability. Despite the good treatment coverages,
      however, many potential vectors are still found infected with Onchocerca volvulus
      and many Ugandans have O. volvulus in their skin. There is now evidence that
      adult O. volvulus can be eliminated, within a period of about 6 years, through
      semiannual treatment with ivermectin. Together, the isolated foci where vector
      elimination is not considered feasible have a human population of about 700,000,
      most of whom (595,000) are eligible to receive ivermectin treatment. The
      estimated cost of each treatment, via the Ugandan CDTI, is U.S.$0.78 if the
      salaries of the government-employed personnel and the working time lost by the
      volunteers who act as community-directed drug distributors (CDD) are taken into
      account. If these 'expenses' are ignored, however, the cost falls to just
      U.S.$0.17/treatment, and the total costs for the four isolated foci where vector
      control is not likely to be successful become about U.S.$101,150/year for annual
      treatment (for an indefinite period of time) or approximately U.S.$202,300/year
      for semi-annual treatment (for the 6 years needed to eliminate adult O.
      volvulus), which would be the more cost-effective option. With the necessary
      financial support and the continued free supply of ivermectin from Merck, the
      national onchocerciasis-control programme could eliminate human onchocerciasis
      from Uganda, through a combination of semi-annual treatment with ivermectin in
      the isolated foci where S. neavei s.s. elimination is not feasible, and vector
      elimination in all the other foci.

PMID- 17524248
TI  - Impact of the 2004 mass drug administration for the control of lymphatic
      filariasis, in urban and rural areas of the Western province of Sri Lanka.
AB  - Lymphatic filariasis is targeted to be eliminated globally, at least as a public
      health problem, by 2020. The comprehensive strategy for achieving this goal
      includes the interruption of the transmission of the causative parasites, by
      drastically reducing the prevalences of microfilaraemia in at-risk communities.
      In a descriptive, comparative, cross-sectional and community-based study, the
      impact of the 2004 mass drug administration (MDA) on filarial infection, in
      selected areas of the Western province of Sri Lanka, has now been assessed 1-2
      and 11 months after the administration of the diethylcarbamazine-albendazole
      combination employed. Using the cluster-sampling method, urban study populations
      were selected in the Colombo districts and rural ones were selected in the
      Gampaha district. After obtaining informed written consent, 2 ml venous blood
      were collected, between 20.00 and 24.00 hours, from each subject. Personal
      details and drug compliance in the 2004 MDA were recorded. The samples of 'night'
      blood were checked for microfilariae, using membrane filtration, and for filarial
      antigenaemia, using commercial (NOW) immunochromatographic test kits. Eighty-four
      (4.10%) of the 2034 subjects examined 1-2 months after the 2004 MDA but only four
      (0.20%) of the 1974 subjects checked 11 months after the MDA were found
      antigenaemic and/or microfilaraemic (P<0.001). Between the two follow-ups, the
      overall prevalences of both antigenaemia (4.03% v. 0.15%; P<0.001) and
      microfilaraemia (0.20% v. 0.05%; P=0.38) fell, although only the reduction in
      antigenaemia was statistically significant. The prevalence of infection (as
      indicated by antigenaemia and/or microfilaraemia) fell significantly within each
      of the two study districts (P<0.001). Although, when the prevalence of infection
      was high, drug compliance appeared to be an important determinant of the
      reduction of antigenaemia (P=0.04), the 20% difference in compliance between
      urban and rural areas had no apparent effect on the corresponding prevalences of
      infection recorded at either follow-up.

PMID- 17524249
TI  - HIV and parasitic co-infections in tuberculosis patients: a cross-sectional study
      in Mwanza, Tanzania.
AB  - A cross-sectional study was conducted in Mwanza, Tanzania, to determine the
      burden of HIV and parasitic co-infections among patients who were confirmed or
      suspected cases of pulmonary tuberculosis (PTB). Of the 655 patients
      investigated, 532 (81.2%) had been confirmed as PTB cases, by microscopy and/or
      culture (PTB+), whereas the other 123 (18.8%) were only suspected cases, on the
      basis of other clinical criteria (PTB-). Hookworm and Schistosoma mansoni
      infections were common in the patients, with prevalences of 18% and 34%,
      respectively. Malarial, Ascaris lumbricoides, Trichuris trichiura and
      Strongyloides stercoralis infections were less common, each recorded at a
      prevalence of <5%. The PTB+ patients were less likely to be HIV-positive than the
      PTB- patients (43.6% v. 62.6%; P<0.0001). Among the PTB+ patients, the HIV
      positive had a significantly lower prevalence (12.1% v. 25%; P<0.0001) and mean
      intensity (49 v. 123 eggs/g; P=0.003) of hookworm infection than the HIV
      negative. The PTB patients in the study area were, however, still frequently co
      infected with HIV and with parasitic infections that may increase morbidity and
      accelerate the progression of HIV disease.

PMID- 17524250
TI  - The diel oviposition periodicity of Aedes aegypti (L.) (Diptera: Culicidae) in
      the laboratory: density disturbance.
AB  - The diel oviposition periodicities of the LSHTM and Trinidad strains of Aedes
      aegypti were studied under laboratory conditions, using different mosquito
      densities in the cages and monitoring at 2-h intervals. With both strains, the
      peak in oviposition occurred earlier in the day when there was only one female in
      a test cage (16.00-18.00 hours) than when 25 or 500 females were held in a cage
      (18.00-20.00 hours). It therefore appears that the numbers of females in the
      cages can affect the diel oviposition periodicity of Ae. aegypti in the
      laboratory and that, therefore, caution is necessary when using and comparing
      data from related laboratory studies in which the ovipositing mosquitoes have
      been held at various densities.

PMID- 17524251
TI  - Molluscicidal activities of six species of Bignoniaceae from north-eastern
      Brazil, as measured against Biomphalaria glabrata under laboratory conditions.
AB  - The molluscicidal profile and brine-shrimp bio-activity of the ethanolic extracts
      of plants from the Bignoniaceae family were determined. The six extracts
      investigated were of the stems of Melloa quadrivalvis and Tabebuia aurea, and
      whole plants of Adenocalymma comosum, Arrabidaea parviflora, Cuspidaria argentea
      and Clytostoma binatum. When tested in the laboratory, with Biomphalaria glabrata
      as the test snail, all six extracts gave median lethal concentrations (9-54
      microg/ml) that fell well below the upper threshold, of 100 mug/ml, set for a
      potential molluscicide by the World Health Organization.

PMID- 17524252
TI  - Preliminary entomological observations in a highland area of Amhara region,
      northern Ethiopia, with epidemic visceral leishmaniasis.

PMID- 17524253
TI  - Diurnally subperiodic Wuchereria bancrofti in the Nicobar Islands, India:
      evaluating the true prevalence of microfilaraemia.

PMID- 17524254
TI  - Oscillatory depth as a function of temporal frequency.
AB  - The percept of oscillatory motion in depth was generated by a luminance
      modulation of a sinusoidal nature induced within each dot pair of a stationary
      random assembly of paired dots. The dots were miniature sources of polarized
      light viewed through a rotating ocular polarizer, which facilitated both the
      percept of oscillations and the modulation of luminance at any desired frequency.
      Depth responses were studied as a function of frequency within the 0-2 Hz range.
      A strong amplitude decrease was noticed at a mean frequency of f(1)=0.81 Hz;
      oscillations were perceived as 'rectified' for f > f(1) with an additional
      minimum of crossed-disparity depth at f(2)=1.60 Hz. It is suggested that the
      intensity modulation of the light beams mapping the stationary stimuli onto the
      retinae was a likely factor responsible for the observed depth minima and the
      rectification of faster oscillations. Results are compared to those obtained in a
      traditional setting, where the percept of oscillations in depth had been
      generated by disparity variations due to lateral motion of the stimuli.

PMID- 17524255
TI  - A comparison of fixed-step-size and Bayesian staircases for sensory threshold
      estimation.
AB  - Fixed-step-size (FSS) and Bayesian staircases are widely used methods to estimate
      sensory thresholds in 2AFC tasks, although a direct comparison of both types of
      procedure under identical conditions has not previously been reported. A
      simulation study and an empirical test were conducted to compare the performance
      of optimized Bayesian staircases with that of four optimized variants of FSS
      staircase differing as to up-down rule. The ultimate goal was to determine
      whether FSS or Bayesian staircases are the best choice in experimental
      psychophysics. The comparison considered the properties of the estimates (i.e.
      bias and standard errors) in relation to their cost (i.e. the number of trials to
      completion). The simulation study showed that mean estimates of Bayesian and FSS
      staircases are dependable when sufficient trials are given and that, in both
      cases, the standard deviation (SD) of the estimates decreases with number of
      trials, although the SD of Bayesian estimates is always lower than that of FSS
      estimates (and thus, Bayesian staircases are more efficient). The empirical test
      did not support these conclusions, as (1) neither procedure rendered estimates
      converging on some value, (2) standard deviations did not follow the expected
      pattern of decrease with number of trials, and (3) both procedures appeared to be
      equally efficient. Potential factors explaining the discrepancies between
      simulation and empirical results are commented upon and, all things considered, a
      sensible recommendation is for psychophysicists to run no fewer than 18 and no
      more than 30 reversals of an FSS staircase implementing the 1-up/3-down rule.

PMID- 17524256
TI  - Which geometric model for the curvature of 2-D shape contours?
AB  - We investigated the geometric representations underlying the perception of 2-D
      contour curvature. 88 arcs representing lower and upper halves of concentric
      circles, or halves of ellipses derived mathematically through planar projection
      by affinity with the circles, a special case of Newton's transform, were
      generated to produce curved line segments with negative and positive curvature
      and varying sagitta (sag) and/or aspect ratio. Aspect ratio is defined here as
      the ratio between the sagitta and the chord-length of a given arc. The geometric
      properties of the arcs suggest a regrouping into four structural models. The 88
      stimuli were presented in random order to 16 observers eight of whom were
      experienced in the mathematical and visual analysis of 2-D curvature ('expert
      observers'), and eight of whom were not ('non-expert observers'). Observers had
      to give a number, on a psychophysical scale from 0 to 10, that was to reflect the
      magnitude of curvature they perceived in a given arc. The results show that the
      subjective magnitude of curvature increases exponentially with the aspect ratio
      and linearly with the sagitta of the arcs for both experts and nonexperts.
      Statistical analysis of the correlation coefficients of linear fits to individual
      data represented on a logarithmic scale reveals significantly higher correlation
      coefficients for aspect ratio than for sagitta. The difference is not significant
      when curves with the longest chords only (7 degrees -10 degrees ) are considered.
      The geometric model that produces the best psychometric functions is described by
      a combination of arcs of vertically and horizontally oriented ellipses,
      indicating that perceptual sensations of 2-D contour curvature are based on
      geometric representations that suggest properties of 3-D structures. A 'buckled
      bar model' is shown to optimally account for the perceptual data of all observers
      with the exception of one expert. His perceptual data can be linked to a more
      analytical, less 'naturalistic' representation originating from a specific
      perceptual experience, which is discussed. It is concluded that the structural
      properties of 'real' objects are likely to determine even the most basic
      geometric representations underlying the perception of curvature in 2-D images. A
      specific perceptual learning experience may engender changes in such
      representations.

PMID- 17524257
TI  - Distortion of apparent shape of an object immediately before saccade.
AB  - 'Perisaccadic mislocalization' is an illusion in which a stimulus presented
      briefly near the time of saccade onset is mislocalized. The amount of
      mislocalization depends on the stimulus location and the stimulus onset time
      relative to saccade onset. It is unclear whether perisaccadic mislocalization
      distorts the shape perception of a single object. To investigate this problem, we
      asked participants to report whether the apparent shape of a triangle presented
      for 10 ms before saccade was slanted in the same direction or the opposite
      direction as the saccade. The results showed that the apparent shape of the
      triangle was distorted in the direction opposite to the saccade. We compared this
      apparent distortion with the mislocalization of a perisaccadic vertical bar, and
      found that the time-course and direction of the distortion were similar, although
      the amount of distortion was smaller for the triangle. A hypothetical explanation
      for these results based on the forward/inverse optics model was discussed.

PMID- 17524259
TI  - [More studies on diagnostic pathology of liver diseases].

PMID- 17524258
TI  - Gradient direction dependencies in natural images.
AB  - We have used information-theoretic measures to compute the amount of dependency
      which exists between two and three gradient directions at separate locations in
      an ensemble of natural images. Control experiments were performed on other image
      classes: phase randomized natural images, whitened natural images and Gaussian
      noise images. The results show that, for an ensemble of natural images, the
      amount of 2-point and 3-point gradient direction dependency is equivalent to its
      ensemble of phase randomized natural images. Therefore, we conclude that the
      amount of gradient direction dependency in an ensemble of natural images is
      determined by the ensemble's mean power spectrum rather than the phase spectra of
      the images. Moreover, this relationship does not extend to individual natural
      images, the amount of dependency between gradient magnitudes, or gradient
      directions at high gradient magnitude locations.

PMID- 17524260
TI  - [Histopathological changes in livers of patients with chronic severe hepatitis
      B].
AB  - OBJECTIVE: To investigate the histopathological features in livers of chronic
      severe hepatitis B (CSHB) patients. METHODS: Histology of 42 livers was studied.
      HE, Masson, Sweet and D-PAS staining and cytokeratin 7, CD68 and proliferating
      cell nuclear antigen immuno-histochemical staining were used in the study.
      RESULTS: In CSHB, the livers showed massive or submassive necrosis in a
      background of other histological changes of chronic hepatitis B. The
      characteristic pictures of these livers were necrosis of all the hepatocytes in
      some nodules, while in other nodules there were only patchy necroses of the
      parenchyma. In some other nodules the necrotic hepatocytes were all removed and
      only the scaffolding stroma remained. Meanwhile, regeneration of hepatocytes and
      bile ductules were also seen. CONCLUSIONS: The liver histopathological changes in
      CSHB are identical, but not of the same degree as those of acute severe and
      subacute severe hepatitis B. In making differential diagnoses for liver
      aspiration biopsies of these patients, this fact should be kept in mind.

PMID- 17524261
TI  - [Liver pathological changes and clinical features of patients with chronic
      hepatitis B virus infection in their immune tolerant phase and non-active
      status].
AB  - OBJECTIVE: To investigate the liver pathological changes and the clinical
      features of patients with hepatitis B virus (HBV) infection in their immune
      tolerant phase and non-active status. METHODS: Fifty-four patients with chronic
      HBV infection in their immune tolerant stage and another 47 patients with the
      same infection but in non-active status were involved in this study. Statistical
      analysis including the ages and sex of the patients, their serum levels of HBV
      DNA, hepatocytic expression of HBsAg and HBcAg and their liver pathology were
      studied and statistically analyzed. Histological grading of inflammation and
      staging of fibrosis in the livers were also compared and analysed in patients
      with different levels of serum ALT. RESULTS: The sex ratio of the two groups was
      of no significant difference. The average age of the patients in the non-active
      status [(28.11+/-8.60) years.] was older than that of the patients in the immune
      tolerant stage [(24.93+/-7.21) years], showing a significant difference (P <
      0.05). The serum levels of HBV DNA of the patients in the immune tolerant stage
      were high and 94% of them had a HBV DNA higher than 106 copies/ml. In the non
      active status group, 89% of the patients were HBV DNA negative. Between the two
      groups of patients there were no significant differences in the histological
      grades of liver inflammation or in the hepatocytic expressions of HBsAg and
      HBcAg. The stage of fibrosis was higher in the non-active status group than in
      the immune tolerant stage group, showing a significant difference between these
      two groups (u = 2.004, P < 0.05). The fibrosis stages of the livers of patients
      of a higher but within normal ALT level were markedly higher than those of a
      lower but within normal ALT level patients (u = 3.274, P less than 0.01).
      CONCLUSION: Patients infected with HBV in non-active status may have experienced
      some occult courses of immune active stages; they are older in age and have
      higher levels of fibrosis. ALT sustained at a high level but within the normal
      range may indicate a higher degree of fibrosis, therefore liver pathological
      studies should be recommended for this kind of patient.

PMID- 17524262
TI  - [A study on the hepatic histological changes and clinical manifestations in
      chronic HBV carriers].
AB  - OBJECTIVE: To investigate the relationship between hepatic histopathological
      changes and clinical characteristics in chronic HBV carriers. METHOD: A
      retrospective analysis was performed based on the hepatic biopsy findings,
      clinical laboratory results, and ultrasound examinations in 142 chronic HBV
      carriers. The patients were divided into two groups according to their serum HBV
      DNA replication and the pathological alterations in their livers. RESULTS: The
      average age of the 142 patients was (24.8+/-8.7) years old. Among them, 129 were
      diagnosed as chronic HBV carriers based on their positive HBV DNA results.
      Thirteen were diagnosed as non-active HBsAg carriers. Hepatitis B family history
      was found in 31.0% of the cases. Normal liver tissues (G0S0) were found in the
      specimens of 33 cases (G > or = 1 and/or S > or = 1) chronic hepatitis B was
      diagnosed based on the biopsies in 106 cases, including an early stage of hepatic
      cirrhosis in 1 case (G4S4). There were no obvious differences between HBV DNA
      positive and negative group cases. The levels of HBV DNA in all the 129 cases of
      chronic HBV carriers were more than 1.0 x 10(4) copy/ml and the average value was
      (7.58+/-0.99) log10 copy/ml. Of the 129 cases, 123 were HBeAg positive (95.3%).
      Increased levels of gamma-globulin were detected in 45.8% of the cases and
      fibrosis index increased in 37.1%; 40.1% of the cases showed abnormalities in
      their ultrasound examinations. The average PCIII value of the chronic HBV carrier
      group (G > or = 1 and/or S > or = 1) was higher than that of the non-active HBsAg
      carrier group (P = 0.016). Spearman's analysis indicated that the inflammation
      grade (G) was correlated with the hepatic fibrosis index PCIII, and the
      correlation coefficient was 0.391 (P = 0.003). CONCLUSION: The patients in our
      study have a higher HBV DNA replication in their sera and have mild inflammation
      in their livers. Inflammation grade (G) and fibrosis stage (S) have no
      correlation with the level of HBV DNA or the state of HBeAg positivity. The
      increased level of PCIII might be related to their hepatic inflammation.

PMID- 17524263
TI  - [Liver histopathological features of chronic HBV carriers and inactive HBsAg
      carriers].
AB  - OBJECTIVE: To study the liver histopathological features of chronic HBV carriers
      and inactive HBsAg carriers. METHODS: Liver biopsies were performed on 189
      chronic HBV carriers and 30 inactive HBsAg carriers (219 cases in total). All of
      them had a normal serum ALT value; they were then followed-up for more than 6
      months. HBsAg and HBcAg were detected by immunohistochemistry. The circulating
      HBV DNA loads and serologic markers of HBV were examined at the same time. Grades
      of liver necrosis/inflammation and fibrosis were compared between the patients
      regarding their HBV DNA positivity or negativity. The relationships between the
      HBeAg positivity and degrees of liver histological changes were evaluated. The
      grades of liver necrosis/inflammation and fibrosis were compared between three
      age groups: younger than 18 years, 18-40, and older than 40 years. RESULTS: Two
      hundred eight carriers of the total 219 (95.0%) had histological liver changes.
      Fifty percent (104/208) of them had mild histological changes (G0-1/S0-1), while
      more severe changes (G3-4 and/or S3-4) were found in 18 out of the 208. There
      were no significant differences in the grades of liver necrosis/inflammation and
      fibrosis between the chronic HBV carriers and the inactive HBsAg carriers. Among
      the serologic HBV DNA positive carriers, hepatic fibrosis was more severe in the
      HBeAg negative group than in the positive group (chi2 = 9.551, P = 0.008), but no
      differences of the necrosis/inflammation grades were seen between the two groups.
      The rate of severe fibrosis (S3-4) was 21.1% in those carriers older than 40
      years but was 7.7% in patients younger than 18 years. However, no statistically
      significant differences in degrees of liver inflammation and fibrosis were found
      among the three age groups. HBcAg positive rate was 100% in the liver tissues of
      all the chronic HBV carriers, but only in 33.3% in the inactive HBsAg carriers.
      CONCLUSIONS: The majority of our HBV carriers have liver inflammation and
      fibrosis. More severe histological changes were found in 8.65% of them. Liver
      fibrosis existed in the carriers with negative HBeAg and in those older than 40
      years. HBcAg was found in hepatic tissues while their serological HBV DNA was
      negative.

PMID- 17524264
TI  - [The relationship between 31P magnetic resonance spectroscopy and the
      histopathology of livers of chronic viral hepatitis patients].
AB  - OBJECTIVE: To investigate the correlations between 31P-magnetic resonance
      spectroscopy (MRS) findings and histopathological grading and staging of the
      livers of chronic viral hepatitis patients. METHODS: Thirty-one patients with
      chronic viral hepatitis and 18 healthy volunteers were enrolled for this study.
      All of them underwent routine MRI plain scan and 31P-MRS of their livers. Peak
      areas of PME, PDE, PCr, Pi, gamma-ATP, beta-ATP and alpha-ATP were calculated.
      The concentrations of the phosphorus compounds of their livers, including PME,
      PDE, PCr, Pi, gamma-ATP, beta-ATP and alpha-ATP were measured. Percutaneous liver
      biopsies were performed on all 31 patients 0 to 7 days after their 31P-MRS
      examinations. Biopsy specimens were scored for fibrosis and necroinflammation
      according to the Knodell histological activity index. According to their
      necroinflammation scores, the 31 patients were divided into groups: slight
      hepatitis (7 patients), mild hepatitis (11), moderate hepatitis (8) and severe
      hepatitis (5). According to their fibrosis scores, the patients were divided into
      groups: no fibrosis (7 patients), portal fibrosis (11), bridging fibrosis (5) and
      cirrhosis (8). RESULTS: The PME%, PDE% and PME/PDE of the hepatitis patients and
      of the control volunteers had significant statistical differences. The
      differences of PME%, PDE% and PME/PDE among different grades and stages also had
      statistical significance. When PME/PDE=0.78, 0.95 and 1.11 were set as the cut
      off points for different grades of necroinflammation, and PME/PDE=0.79, 0.95 and
      1.10 were set as the cut-off points for different stages of fibrosis, a
      sensitivity of 80.0%-87.5% and a specificity of 42.9%-72.7% were achieved.
      CONCLUSION: PME/PDE is a sensitive marker for diagnosing the severity of chronic
      viral hepatitis. A rise of PME/PDE in hepatitis patients represents an increase
      of synthesis and a decrease in the breakdown of hepatocytes.

PMID- 17524265
TI  - [The degree of HBV suppression with 24 week telbivudine- or lamivudine-treatment
      in hepatitis B patients predicts the efficacy of the treatment at week 52].
AB  - OBJECTIVES: To investigate the possibilities of an association between the
      degrees of HBV suppression with nucleoside treatments at week 24 and week 52 in
      hepatitis B patients and to find a useful predictor for treatment efficacy.
      METHODS: In this phase III, double-blind, multicenter trial, we compared the
      efficacy of telbivudine treatment with lamivudine treatment in 332 Chinese
      compensated chronic hepatitis B patients. The patients were randomly assigned to
      a daily 600 mg telbivudine treatment group or daily 100 mg lamivudine group for
      24 weeks. They were then categorized into 4 groups according to their serum HBV
      DNA levels (copies/ml) at week 24: a PCR-undetectable group (< 300 copies/ml); a
      QL- < 10(3) copies/ml group; a 10(3)-<10(4) copies/ml group; and a > or = 10(4)
      copies/ml group. The treatments were continued as they previously had been for
      another 28 weeks and the patients serum HBV DNA levels were examined again.
      RESULTS: At week 52, mean reductions of serum HBV DNA were significantly greater
      in the telbivudine-treated patients than in the lamivudine-treated group (6.2
      log10 vs 5.4 log10, t = 3.6, P < 0.01). Viral resistance was twice as common in
      lamivudine-treated patients compared to those receiving telbivudine. Telbivudine
      was well-tolerated with an adverse event profile similar to that of lamivudine.
      The lower the HBV DNA level achieved at week 24, the higher HBV DNA non
      detectable by PCR. ALT normalization and HBeAg seroconversion achieved at week
      52, and viral resistance at week 48 decreased parallel to the degree of HBV DNA
      inhibition. CONCLUSION: HBV DNA PCR-undetectable at week 24 in nucleoside-treated
      hepatitis B patients suggests a better efficacy at week 52 and lower viral
      resistance at week 48. The degree of suppression of HBV at week 24 may be used as
      a predictor of 1-year outcome.

PMID- 17524266
TI  - [Three year adefovir dipivoxil treatment for hepatitis B e antigen-positive
      chronic hepatitis B patients].
AB  - OBJECTIVES: To evaluate the efficacy and safety of adefovir dipivoxil (ADV)
      treatment in patients with hepatitis B e antigen (HBeAg) positive chronic
      hepatitis B (CHB). METHODS: This was a multicenter, randomized, double-blind,
      placebo-controlled study. It was performed in four steps. First step: subjects
      were randomly assigned to receive either ADV 10 mg once daily (QD) or matching
      placebo tablets in a 3:1 ratio for 12 weeks. Second step: at week 12, all
      subjects started to have open-label ADV 10 mg QD for 28 weeks. Third step:
      subjects who received ADV in the first 12 weeks were rerandomized to receive
      either ADV or a placebo in a 2:1 ratio for 12 weeks and subjects who initially
      received a placebo continued to receive open-label ADV, but they were further
      assigned into 3 groups: A, B and C. In group A (12 patients), they received a
      placebo for the first 12 weeks and then ADV for the following 40 weeks. In group
      B (24 patients), they received ADV for the entire 52 weeks. In group C (12
      patients), they received ADV in the first 40 weeks and a placebo in the last 12
      weeks. Fourth step: all subjects restarted open-label ADV 10 mg QD for 208 weeks.
      RESULTS: (1) At week 12, the median decrease in serum HBV DNA levels was 3.7
      log10 copies/ml in the ADV group and 0.2 log10 copies/ml in the placebo group (P
      < 0.01). (2) At week 12, serum ALT normalization was observed in 10 of the 36
      subjects (27.8%) in the ADV group and 0 of the 11 subjects (0%) in the placebo
      group (P < 0.05). (3) In group B the proportion of subjects with serum ALT
      normalization increased to 66.7% at week 52. As for virological parameters in
      those subjects rerandomized to a placebo for weeks 40-52 (group C), biochemical
      benefit was rapidly lost (ALT normalization dropped from 50.0% to 25.0%). (4) At
      week 40, the median reduction in serum HBV DNA was similar across all treatment
      groups. In subjects rerandomized to ADV (group A and B), there were further
      reductions in serum HBV DNA from -3.2 to -3.6 and from -4.4 to -4.6 log10
      copies/ml, respectively at week 52. In contrast in subjects rerandomized to a
      placebo during weeks 40-52 (group C), the median reduction in serum HBV DNA
      decreased from -3.7 to -0.7 log10 copies/ml at week 52. (5) In week 40, the
      proportion with undetectable HBV DNA (< 300 copies/ml) was similar in these three
      groups, while at week 52, the proportion with undetectable HBV DNA (< 300
      copies/ml) in group C was 0%. (6) At week 52, the proportion with HBeAg loss in
      group B was 12.5% (3/24). The ratios of HBeAg seroconversion and HBeAg
      seroconversion with HBV DNA < or = 10(5) copies/ml were both 8.3%. (7) At week
      104, the median reduction in serum HBV DNA was -4.2 log10 copies/ml, which was 
      4.3 log10 copies/ml at week 156. The proportion with undetectable HBV DNA (< 300
      copies/ml) was both 31.0% at week 104 and week 156. The proportion of subjects
      with serum ALT normalization was 46.3% at week 104, which was 86.4% at week 156.
      The proportion with HBeAg loss was 23.8% at week 104, which was 31.0% at week
      156. The proportion with HBeAg seroconversion was 23.8%. (8) No renal toxic
      effects were observed. CONCLUSION: The treatment with 10 mg ADV QD over 156 weeks
      was safe and effective in patients with HBeAg-positive CHB.

PMID- 17524267
TI  - [The simultaneous knock-down of Ku70 and Ku80 by a tandem Ku-shRNA-encoding
      plasmid expression system].
AB  - OBJECTIVE: To extend the use of vector-derived siRNA by generating multiple
      shRNAs in the same plasmid. METHODS: Construct a vector that expresses shRNAs
      targeting on Ku70 and Ku80 in tandem. The gene silencing efficiency of each shRNA
      was verified previously. After identification by restriction digestion and DNA
      sequencing, the reconstructed plasmid, named psiRNAKus, was transfected into the
      human hepatoma cell line HepG2. The tandem-shRNA-induced silencing of targeted
      genes was determined by RT-PCR at RNA level and Western blot at protein level.
      RESULTS: The shRNAs encoded by psiRNAKus down-regulated both the expression of
      Ku70 and Ku80. CONCLUSION: The vector-derived siRNA delivery system that allows
      multiple shRNA species to be expressed from the same vector may be of value in
      experimental and therapeutic applications.

PMID- 17524268
TI  - [Changes of Toll-like receptor (TLR) 2 and TLR4 on the peripheral blood
      mononuclear cells in patients with chronic hepatitis B and chronic severe
      hepatitis B].
AB  - OBJECTIVE: To study the changes of TLR2 and TLR4 on peripheral blood mononuclear
      cells (PBMCs) and their role in the pathogenesis of chronic hepatitis B and
      chronic severe hepatitis B. METHODS: The expressions of TLR2 and TLR4 on 10000
      CD14+ PBMCs were determined by flow cytometry in 30 healthy controls, in 31
      patients with chronic hepatitis B and in 30 patients with chronic severe
      hepatitis B. The level of serum tumor necrosis factor alpha (TNF alpha) was
      determined by ELISA. The differences of expression of TLR2 and TLR4 on PBMCs and
      serum TNFalpha among the three groups of study subjects were determined by
      Student-t test. The correlations between TLR2, TLR4 and TNF alpha were determined
      by linear correlation test. RESULTS: The values of mean fluorescence intensity
      (MFI) of TLR2 on PBMCs of the healthy controls, patients with chronic hepatitis B
      and patients with chronic severe hepatitis B groups were 21.5+/-2.7, 39.0+/-4.1,
      and 47.7+/-21.4; TLR4 of those groups was 2.3+/-1.1, 3.7+/-2.3, and 6.9+/-4.1.
      The serum TNF alpha(ng/L) of the respective groups was 53.8+/-38.1, 164.3+/-89.9,
      and 359.8+/-140.0. There was a gradual increase of these values from the group of
      healthy controls to the group of patients with chronic hepatitis B and patients
      with chronic severe hepatitis B. No significant positive correlations between
      TLR2, TLR4 and serum TNFalpha were found. CONCLUSION: TLR2 and TLR4 may have a
      role in the pathogenesis of chronic hepatitis B and chronic severe hepatitis B.

PMID- 17524269
TI  - [Evaluation of interventional therapy for hepatocellular carcinoma with
      arteriovenous fistulas: an analysis of 38 cases].
AB  - OBJECTIVE: To evaluate the therapeutical effects and techniques of superselective
      arterial embolization in hepatocellular carcinoma (HCC) patients with
      arteriovenous fistulas (AVFs). METHODS: Data from 425 cases of HCC patients
      treated with transcatheter arterial chemoembolization (TACE) in our hospital
      during the last 2 years were analyzed. Ethanol and/or ethanol and gelfoam (into
      AVFs), ethanol and/or lipiodol (1:1) or lipiodol and 2 to 3 other kinds of
      chemodrugs (into tumors) were used to do the transcatheter superselective
      arterial embolization. RESULTS: AVFs were found in 38 of our 425 HCC cases
      (8.9%). Among those 38 cases, 21 (55%) had high flux APFs and 17(45%) had low
      flux APFs. Eight patients (21% of the 38) had both AVFs and hepatic artery
      hepatic venous fistulas. AVFs and tumors of the 38 cases were successfully
      superselectively embolized, but 35 of the 38 cases had 2-3 procedures. After
      treatment, hepatic functions improved in 23 cases (61%), ascites disappeared in
      13 cases (32%) and ascites decreased in 20 cases (53%). The survival rates at 6
      months and 1 year were 84% (32/38) and 61% (23/38). CONCLUSION: Superselective
      embolization procedure is beneficial in relieving portal high pressure and its
      serious consequences in HCC patients with APFs; it is also a foundation for TACE.
      The procedure can improve the quality of life and the survival rate of the
      patients.

PMID- 17524270
TI  - [Heat-shock protein 27 linked to multi-drug resistance in human hepatic cancer
      cell lines].
AB  - OBJECTIVE: A proteomics approach was applied for finding multi-drug resistance
      (MDR) related proteins in hepatic cancer cell lines. METHODS: Two-dimensional
      electrophoresis (2-DE) was used to separate the total proteins of vincristine
      resistant hepatic cancer cell line HepG2/VCR and its counterpart HepG2. The
      differential expression proteins between the two cell lines were identified by
      both MALDI-TOF-MS and ESI-Q-TOF-MS. Heat-shock protein 27 (HSP27), one of the
      differential expression proteins in the development of MDR of HepG2/VCR, was
      analyzed by HSP27 antisense oligonucleotides (ASOs). RESULTS: As a high
      expression protein in HepG2/VCR, HSP27 was identified, and the suppression of
      HSP27 expression by HSP27 ASO enhanced the vincristine chemosensitivity of
      HepG2/VCR (P less than 0.05). CONCLUSION: HSP27 is linked to MDR in human hepatic
      cancer cell line HepG2/VCR.

PMID- 17524271
TI  - [The expression of peroxiredoxin II in hepatocellular carcinoma and its
      significance].
AB  - OBJECTIVE: To evaluate the mRNA and protein expressions of peroxiredoxin II
      (PrxII) in hepatocellular carcinoma (HCC) and their significance. METHODS: HCC
      was induced by aflatoxin B1 (AFB1) in 6 tree shrews (Tupaia belangeri chinensis).
      The expression levels of PrxII mRNA and protein were detected by reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western blot on HCC tissues
      and on their surrounding liver tissues (para-HCC). Biopsied liver tissues were
      taken before the HCC induction (pre-HCC) from the same animals and from a group
      of blank controlled animals that served as controls. Liver biopsy specimens from
      18 cases of human HCC and from 17 healthy human volunteers were studied using the
      same methods. RESULTS: The mRNA and protein expressions of PrxII in tree shrew
      HCC tissues were significantly higher than those in para-HCC and pre-HCC tissues,
      and also higher than those in the liver tissues from the control animals (all P <
      0.05). The expression levels of PrxII mRNA and protein in human HCC tissues were
      also significantly higher than those in their para-HCC tissues and in the human
      normal liver tissues (P < 0.05). CONCLUSION: PrxII might play an important role
      in hepatocarcinogenesis and might be used as a molecular target for HCC
      prevention and treatment.

PMID- 17524272
TI  - [A clinicopathological analysis of liver retransplantation in 22 cases].
AB  - OBJECTIVE: To analyze the clinical and pathological features of patients with
      liver retransplantation. METHODS: The clinical and pathological data of 22
      patients who had liver retransplantation at our center from October 2003 to June
      2006 were retrospectively analyzed. RESULTS: Among the 523 patients who underwent
      liver transplantation, 22 (4.4%) had liver retransplantation. The causes of liver
      retransplantation were biliary tract complications (13/22), hepatic artery
      thrombosis (3/22), recurrence of hepatocellular carcinoma (5/22) and
      nonfunctional primary graft (1/22). The pathological changes in the livers of
      patients with biliary complications were intrahepatic cholestasis, primary bile
      duct hyperplasia and neutrophil infiltrations. CONCLUSION: Biliary tract
      complications are the main cause of liver retransplantation. Differential
      diagnosis of various complications through early liver puncture biopsy and
      imaging examination will contribute to guide clinical treatment and may help in
      avoiding liver retransplantation.

PMID- 17524273
TI  - [Liver pathology in idiopathic portal hypertension].
AB  - OBJECTIVE: To study the histopathological changes of livers in idiopathic portal
      hypertension (IPH). METHODS: Liver specimens from 29 cases with idiopathic portal
      hypertension were studied. Histological preparations of the livers were stained
      with haematoxylin eosin and Masson's trichrome; reticular fibers in the liver
      tissues were demonstrated. The slides were also stained using some
      immunohistochemistry methods, and the pathological changes of the livers were
      analyzed. RESULTS: The characteristic changes found in these IPH livers were
      dense portal fibrosis; obliteration, with or without phlebitis, of the branches
      of the portal vein; dilatation of the sinusoids; atrophy and nodular hyperplasia
      of liver cells. CONCLUSIONS: Histopathological changes of the livers in IPH are
      dense portal fibrosis, portal vein branch obliteration and nodular hyperplasia of
      liver cells. These are the main features for a histopathological diagnosis of
      IPH.

PMID- 17524274
TI  - [Intrasplenic transplantation of newborn rat hepatocytes with rALR for treating
      rats with acute hepatic failure].
AB  - OBJECTIVE: To evaluate the effects of newborn rat hepatocyte intrasplenic
      transplantation combined with rat augmenter of liver regeneration (rALR)
      injection in treating rats with acute hepatic failure. METHODS: Acute hepatic
      failure (AHF) was induced in rats using D-gal (1.2 g/kg). The rats were then
      randomly divided into 6 groups. Group I received no further treatment and served
      as blank controls; group II received 1 ml buffered saline once through
      intrasplenic injection; group III received 1 ml rALR; group IV received 2 x
      10(7)/ml hepatocytes; group V received 2 x 10(7) hepatocytes suspended in 1 ml
      rALR (50 microg/kg) and group VI received 2 x 10(7) hepatocytes in 1 ml
      cyclosporine A (10 mg/kg). The rats of the various treated groups were sacrificed
      at day 1, 5 and at week 2 and their livers and spleens were examined
      histopathologically. Blood samples of the rats were also obtained to determine
      the levels of TNF alpha and IL-1 beta. RESULTS: There were no significant
      differences in survival between group I, II and III rats. 33.3% of the group IV
      rats survived for 2 weeks. At week 2, the survival rate of group V rats was
      significantly higher than that of group IV, but there was of no statistical
      significant increase when compared to that of group VI rats. Hepatocytes
      transplanted into spleens survived for 5-7 days in the spleens of group IV and VI
      rats, but they survived at least 2 weeks in group V. The average serum TNF alpha
      level in group IV was significantly higher than that in groups V and VI on the
      first postoperative day, but after four days, only the difference between group
      IV and group VI was significant (P < 0.05). The average serum level of TNF alpha
      in group II was higher than that in groups IV, V and VI on the first
      postoperative day (P < 0.05), but there were no significant differences between
      those in groups IV, V and VI on the 1st and the 5th postoperative days.
      CONCLUSION: Newborn rat hepatocyte intrasplenic transplantation combined with
      rALR is effective in treating acute hepatic function failure induced by D-gal in
      rats. The transplanted hepatocytes can survive for at least 2 weeks in the
      spleens. The rALR mixed with the hepatocytes injected into the spleens may be
      able to facilitate the hepatocyte regeneration, to inhibit liver cell apoptosis
      and to suppress the cellular immunity.

PMID- 17524275
TI  - [Points in pathological diagnosis of chronic hepatitis].

PMID- 17524276
TI  - [Some important issues on liver pathology when planning liver transplantation].

PMID- 17524277
TI  - [The effects of variations of HBV S gene on its RNA secondary structure in
      serious hepatitis B patients].

PMID- 17524278
TI  - [The expression of cannabinoid receptor 1 in fibrotic liver tissues of mice
      infested with Schistosoma mansoni].

PMID- 17524279
TI  - [A study on inhibiting hepatocellular carcinoma invasion with c-met-siRNA induced
      by retrovirus in vivo].

PMID- 17524280
TI  - [Systemic inflammatory response syndrome and related inflammatory mediators in
      severe viral hepatitis].

PMID- 17524281
TI  - [Effects of rat recombinant leptin on gene expression of collagen I and tissue
      inhibitor of metalloproteinase 1 in HSC-T6 cells].

PMID- 17524282
TI  - [Progress in the study of recurrent primary biliary cirrhosis after orthotopic
      liver transplantation].

PMID- 17524283
TI  - [Natural killer T cells and liver diseases].

PMID- 17524284
TI  - Chaperones: protecting the patient or protecting the doctor?
AB  - The routine use of chaperones during medical examinations, including intimate
      examinations, is variable. Practice varies between countries and also within
      them. Use of a chaperone may protect patients from sexual abuse by medical or
      nursing practitioners. An appropriate chaperone may also protect healthcare
      practitioners from false accusations. This article considers issues surrounding
      the use of chaperones and suggests a chaperoning policy for sexual health
      clinics, while acknowledging that it may not be appropriate or acceptable to all
      patients or medical staff, or for different parts of the world.

PMID- 17524285
TI  - An extra pair of eyes: do patients want a chaperone when having an anogenital
      examination?
AB  - BACKGROUND: Anogenital examinations can be embarrassing for patients and can
      leave clinicians open to accusations of professional misconduct. Little is known
      about the attitudes of patients in Australia towards the use of chaperones.
      METHODS: In 2006, we surveyed 480 patients attending two sexual health clinics in
      northern Sydney. Our aim was to determine their attitudes towards the use of
      chaperones for anogenital examinations. RESULTS: Of the 480, 58% were male and
      42% female. Most women (64%) preferred a female examining clinician, whereas most
      men (68%) had no preference for gender of the examining clinician (P < 0.0001).
      While 32% of women wanted a chaperone if being examined by a male, 29% did not.
      Only 4% of women wanted a chaperone when being examined by a female. Only 1% of
      men wanted a chaperone irrespective of the sex of the examining clinician.
      Independent predictors of women wanting a chaperone with a male clinician were
      preference for a female clinician (OR 6.59, 2.48-17.5; P < 0.001) and preference
      for a female chaperone (OR 4.02, 1.44-11.2; P = 0.008). The majority of
      participants felt that they should be involved in the decision to have a
      chaperone. CONCLUSIONS: Although a substantial minority of women want a chaperone
      when being examined by a male, a similar proportion do not want a chaperone. If a
      woman requests a female clinician, she should be offered a chaperone if there is
      only a male examiner available. Further study is required to determine why some
      women want a chaperone and how to distinguish them from other women.

PMID- 17524286
TI  - Australian sexual health practitioners' use of chaperones for genital
      examinations: a survey of attitudes and practice.
AB  - OBJECTIVES: To examine the current practice and attitudes of Australian sexual
      health practitioners towards the use of chaperones for genital examinations.
      METHODS: In July 2006, an anonymous, self-completed questionnaire was mailed to
      members of the Australasian Chapter of Sexual Health Medicine. RESULTS: Of the
      166 questionnaires sent to practitioners, 110 (66%) were returned completed. Of
      the 110 respondents, only 9% and 19% reported that their clinic routinely
      provided chaperones for all male and female genital examinations, respectively.
      Among practitioners whose services did not offer chaperones routinely, chaperones
      were offered with a mean frequency of 19% for female examinations and 8% for male
      examinations (P = 0.01). Compared to female practitioners, significantly more
      male practitioners thought a chaperone was important for medico-legal purposes
      when examining females (72% v. 53%, P < 0.05). Compared to male practitioners,
      significantly more female practitioners thought a chaperone was sometimes
      important for patient support when examining male patients (52% v. 26%, P <
      0.001). Only 39% (n = 18) of male practitioners and 36% (n = 23) of female
      practitioners felt that resources spent on chaperones were justified by the
      benefits they provided. CONCLUSIONS: Despite only a minority of practitioners
      offering chaperones to patients or using them during examinations, many feel they
      are important for medico-legal reasons and as support for the patient. Best
      practice may be for services to routinely offer a chaperone and record instances
      where an offer is declined. This provides patients with choice and practitioners
      with some level of protection.

PMID- 17524287
TI  - Depressive symptoms and condom use with clients among female sex workers in
      China.
AB  - This study examines the association between depressive symptoms and condom use
      with clients among 278 female sex workers (FSW) in Guangxi, China. About 62% of
      these FSW had a high level of depressive symptoms (CES-D total score >or=16).
      Multiple logistic regression analyses indicated that FSW with high level of
      depressive symptoms were less likely to use condoms consistently (aOR = 0.50, 95%
      CI: 0.28-0.89) or use condoms properly (aOR = 0.44, 95% CI: 0.20-0.99). The
      findings suggested that HIV prevention programs targeted at FSW should take into
      consideration the level of depression they experience.

PMID- 17524288
TI  - Pilot of non-invasive (oral fluid) testing for HIV within a clinical setting.
AB  - BACKGROUND: The objectives of the present study were: to determine the
      sensitivity and specificity of oral fluid testing compared with the performance
      of standard blood-based HIV enzyme immunoassay; to assess the feasibility of oral
      fluid specimen collection from clients for the purposes of HIV testing within a
      clinical setting; and to assess the clinical and laboratory impact regarding
      staffing, material resources, expertise and funding of oral fluid testing.
      METHODS: A parallel comparative trial of oral fluid and blood testing was
      conducted among a group of HIV positive clients and a group of unknown HIV
      serostatus clients where each client was offered both tests. An ambulatory HIV
      clinic recruited 175 known HIV positive clients and 179 persons were recruited
      through an inner city sexual health clinic while attending for routine sexual
      health checks. Client responses to oral fluid collection were assessed. The
      sensitivity and specificity of oral fluid testing were calculated. RESULTS: Of
      the 176 confirmed HIV reactive blood test results, the OraSure (OraSure
      Technologies, Beaverton, OR, USA) assay failed to detect only one of these,
      demonstrating a sensitivity of 99.4%. Of the 178 blood specimens that were tested
      as non-reactive by the AxSYM (Abbott Laboratories, Abbott Park, IL, USA) Combo
      system, OraSure recorded four of the corresponding oral fluid specimens as
      reactive (assumed to be false-positive), giving a specificity of 97.6%. Although
      evaluation of patients undergoing the test showed a large proportion (88.6%)
      preferred the OraSure test to conventional blood testing, a large minority of
      these (22.6%) made such a preference conditional on the OraSure test being as
      reliable as current blood testing. CONCLUSIONS: This limited clinic based trial
      of oral fluid testing for HIV antibodies among an outpatient population has
      demonstrated the potential of oral fluid as a specimen for HIV testing. However,
      the lower performance of the test compared with current serum-based tests may
      limit the usefulness of OraSure to epidemiological studies or as an alternative
      screening tool in outreach settings among higher risk populations.

PMID- 17524289
TI  - Macrolide use and the risk of vascular disease in HIV-infected men in the
      Multicenter AIDS Cohort Study.
AB  - BACKGROUND: There has been increasing concern that HIV-infected individuals may
      be more at risk for cardiovascular events in the highly-active antiretroviral
      therapy (HAART) era. This study examined the risk of thromboembolic events in HIV
      infected and non-infected individuals and the effect of macrolide prophylaxis on
      those outcomes. METHODS: A subcohort analysis was undertaken using data collected
      in the Multicenter AIDS Cohort Study to examine the relative risk of vascular
      events (myocardial infarction, unstable angina and ischaemic stroke). Cox
      proportional hazard model using age as the time scale with time varying cofactors
      obtained at each semi-annual visit were used to assess the independent effect of
      macrolide use. RESULTS: Controlling for other significant effects including race
      and smoking, HIV-infection was not independently associated with vascular events.
      Increased risk was observed among those who used HAART (relative hazard 1.09, 95%
      confidence intervals 1.00-1.19 in multivariate model), antihypertensive treatment
      (1.81 [1.26-2.60]), lipid-lowering medication (1.65 [1.12-2.42]), and antibiotics
      (1.72 [1.25-2.36]). The protective association of macrolide use for a vascular
      event in the HAART era was also significant (0.10 [0.01-0.75]). CONCLUSIONS:
      Traditional risk factors are important in the pathogenesis of vascular events in
      HIV-infected individuals. Macrolide antibiotics may have a protective effect in
      the HIV-infected individuals in the HAART era.

PMID- 17524290
TI  - Using hepatitis A and B vaccination as a paradigm for effective HIV vaccine
      delivery.
AB  - BACKGROUND: An understanding of vaccine acceptance and uptake is imperative for
      successful vaccination of populations that will be primary targets for
      vaccination after a vaccine against HIV is developed and ready for dissemination.
      Experiences with vaccination against vaccine-preventable hepatitis (VPH) among
      men who have sex with men (MSM) may offer key insights to inform future HIV
      vaccination strategies. The purpose of this analysis was to explore what is known
      currently about vaccination among MSM, using knowledge gained from vaccination
      against VPH, and to identify important considerations from these experiences that
      must be explored further as a vaccine against HIV is promoted among MSM. Because
      cultural and political differences make it difficult to extrapolate findings from
      studies in one country to another, we have focused our analyses on studies
      conducted in the USA. METHODS: Through a qualitative systematic review of
      published reports, we identified eight studies that reported correlates of VPH
      among MSM in the USA. RESULTS: Six major domains of variables associated with
      vaccination against VPH were identified, including: demographics (e.g. younger
      age, higher educational attainment); increased vaccine knowledge; increased
      access to health care; provider recommendation; behaviours (e.g. same-sex
      behaviour, health-promoting and disease-preventing behaviours); and psychosocial
      factors (e.g. openness about one's sexual orientation, reduced barriers to being
      vaccinated, self-efficacy). CONCLUSIONS: Further research is needed to understand
      vaccination behaviour among MSM and to maximise acceptance and uptake after a
      vaccine exists. Experiences with VPH provide a real-world model on which to base
      preliminary assumptions about acceptance and uptake of a vaccine against HIV.

PMID- 17524291
TI  - Vaccinating young adults against human papillomavirus: the importance of
      understanding health decision-making and behaviour.
AB  - Vaccination of young teenage females against human papillomavirus (HPV) with a
      newly licenced quadrivalent vaccine designed to prevent cervical cancer and
      genital warts has recently been recommended by the Australian government and will
      be implemented through schools from April 2007. In addition, a fully funded
      'catch-up' vaccination program for young women up to age 26 years has been
      approved for a 2-year period, from July 2007. As general practitioners (GPs) will
      be the main immunisation providers for this age group, in order to achieve high
      vaccination coverage and maximal impact on disease, it will be critical for GPs
      to be opportunistic in recommending this vaccine. An initial study of young
      Australians' attitudes towards HPV vaccination and hypothetical acceptance of the
      vaccine was published in this journal. We draw on this study and data published
      elsewhere to discuss issues of HPV vaccine acceptability, and the likely
      challenges of a mass vaccination initiative in this age group in Australia. We
      suggest specific strategies to support GPs, and highlight areas for further
      research in HPV vaccine acceptability.

PMID- 17524292
TI  - Prevalence of Chlamydia trachomatis in a public colposcopy clinic population.
AB  - BACKGROUND: Chlamydia trachomatis is a major public health issue, with
      notifications of this sexually transmitted disease continuing to rise in
      Australia. Women attending colposcopy clinics are referred for treatment of
      cervical abnormalities often associated with human papilloma virus (HPV)
      infection. There is evidence that women who have acquired one sexually
      transmitted infection, such as HPV, are at higher risk of acquiring another.
      Women attending colposcopy clinics may therefore be at risk of undiagnosed
      infection with C. trachomatis. AIM: To determine the prevalence of C. trachomatis
      in women attending a public metropolitan colposcopy clinic in Victoria. METHODS:
      A cross-sectional study was performed. Institutional ethics committee approval
      and informed consent were obtained. Consecutive women attending the colposcopy
      clinic completed a questionnaire and had a swab collected from the endocervix for
      analysis by polymerase chain reaction for C. trachomatis. Positive screens were
      treated in accordance with best practice. Data were analysed with Minitab Version
      2004 (Minitab Inc, State College, PA, USA). RESULTS: Of 581 women approached to
      participate in the trial, consent was obtained from 568 women (98%) and final
      outcome data was available on 560 women (99%). The overall rate of chlamydial
      infection was 2.1% (95% CI 1.5-2.7%). However, in women aged 25 years or less the
      rate was 5.8% (95% CI 3.8-7.8%) and in women over 25 years it was only 0.9% (95%
      CI 0.4-1.4%). Apart from age, no other demographic factor was significantly
      associated with chlamydial infection. CONCLUSION: Although the prevalence of
      chlamydial infection in the colposcopy clinic population as a whole does not
      warrant a policy for routine screening, screening directed at women aged 25 years
      or less would gain the greatest yields in terms of cost efficacy. Such a policy
      should be implemented as standard practice.

PMID- 17524293
TI  - Chlamydia trachomatis prevalence in heterosexual men in Melbourne: a community
      based study.
AB  - There is limited information about chlamydia prevalence in men. Our study aimed
      to measure the prevalence of chlamydia in 16-29-year-old heterosexual men.
      Recruitment was undertaken through urban sporting clubs. Participants were
      approached after training to complete a questionnaire and to provide a urine
      sample that was tested for Chlamydia trachomatis. Participants with positive
      results received treatment. Fifty participants were recruited and four were found
      to be infected (8.5%, 95% CI 2.76-21.27). There was a high prevalence of C.
      trachomatis in our study participants, highlighting the importance of including
      men in chlamydia response programs.

PMID- 17524294
TI  - Chlamydia trachomatis infection among antenatal women in remote far west New
      South Wales, Australia.
AB  - BACKGROUND: A prospective, cross-sectional study was undertaken of pregnant women
      attending antenatal services in the remote far west of New South Wales,
      Australia, between October 2004 and May 2006. Of 420 eligible women, 218 (52%)
      participated in the study. Six women (2.7%; 95% CI: 1.0-5.9) tested positive for
      Chlamydia trachomatis. The prevalence among pregnant, Indigenous women (n = 44)
      was 9.1% (95% CI: 2.5-21.7). Infection was significantly associated with
      Indigenous status (P = 0.003) and self-perceived risk for chlamydia (P = 0.05).
      Pregnant Indigenous women in remote areas may be at higher risk for chlamydia and
      targeted screening of this group should be considered.

PMID- 17524295
TI  - Famciclovir or valaciclovir in the management of herpes simplex and varicella
      zoster infections: an attitudinal survey of clinician perceptions of differential
      activity.

PMID- 17524296
TI  - Uterine and vaginal insemination optimised in brushtail possums (Trichosurus
      vulpecula) superovulated with pregnant mare serum gonadotrophin and porcine
      luteinising hormone.
AB  - Artificial insemination of brushtail possums (Trichosurus vulpecula) is being
      developed as an assisted breeding model for endangered marsupials, as well as a
      bioassay for testing fertility control vaccines to manage overabundant
      populations. Procedures were optimised in animals superovulated with pregnant
      mare serum gonadotrophin (PMSG) and porcine luteinising hormone (pLH). Of three
      intervals examined, yields were maximal following uterine insemination at 27-29.5
      h after pLH treatment (four eggs, two to three embryos per female). Compared with
      no insemination, uterine-inseminated animals ovulated 30-36 h rather than 28-34 h
      after pLH treatment. For the vaginal route, yields were maximal following
      insemination at 10-13 h after pLH treatment (six to seven eggs, four embryos per
      female) than at five other intervals, and when using acclimatised females during
      the autumn breeding season. This protocol was suitable for testing fertility
      control vaccines in April-June and was influenced by the housing location of
      animals, the presence of an active corpus luteum and PMSG batch, but not other
      factors (year of trial, Freund's adjuvant treatment, changes in bodyweight, dose
      of PMSG kg(-1)). Embryos developed to the eight- to 16-cell or unilaminar
      blastocyst stage after uterine or vaginal insemination, respectively. With the
      timing of artificial insemination optimised, new methods to synchronise or induce
      oestrus and ovulation are required to achieve year-round testing of fertility
      control vaccines or birth of offspring.

PMID- 17524297
TI  - Effects of uteroplacental restriction on the relaxin-family receptors, Lgr7 and
      Lgr8, in the uterus of late pregnant rats.
AB  - The peptide hormone relaxin stimulates uterine growth and endometrial
      angiogenesis and inhibits myometrial contractions in a variety of species. The
      receptor for relaxin is a leucine-rich repeat containing G-protein-coupled
      receptor Lgr7 (RXFP1) that is highly expressed in the myometrium of late pregnant
      mice, with a significant decrease in receptor density observed at term. The
      present study first compared the expression of Lgr7 with another relaxin-family
      receptor Lgr8 (RXFP2) in the uterus and placenta of late pregnant rats. The
      uterus was separated into endometrial and myometrial components, and the
      myometrium into fetal and non-fetal sites, for further analysis. We then assessed
      the response of these receptors to uteroplacental restriction (UPR). Expression
      of the Lgr7 gene was significantly higher in the uterus compared with the
      placenta. Within the uterus, on Day 20 of gestation, there was equivalent
      expression of Lgr7 in fetal and non-fetal sites of the myometrium, as well as in
      the endometrium v. myometrium. The second receptor investigated, Lgr8, was also
      expressed in the endometrium and myometrium, but at significantly lower levels
      than Lgr7. Bilateral ligation of the maternal uterine blood vessels on Day 18 of
      gestation resulted in uteroplacental restriction, a decrease in fetal weight and
      litter size, and a significant upregulation in uterine, but not placental, Lgr7
      and Lgr8 gene expression in UPR animals compared with controls. These data
      suggest that both relaxin family receptors are upregulated in response to a
      reduction in uteroplacental blood flow in rats.

PMID- 17524299
TI  - Measuring the effects of wildlife contraception: the argument for comparing
      apples with oranges.
AB  - There are few wildlife populations existing today that can be supported without
      some form of management. Wildlife fertility control, as one option, has moved
      from the research stage to actual application with a number of species, including
      wild horses, urban deer, captive exotic species and even African elephants, but
      this approach remains controversial in many quarters. Strident debate has arisen
      over the possible effects of contraception on behaviour, genetics, stress and
      even management economics, among other parameters. Part of the debate arises from
      the fact that critics often fail to recognise that some form of alternative
      management will be applied, and a second problem arises when critics fail to
      identify and demand the same concern for the consequences of the alternative
      management approaches. Thus, any rational debate on the merits or possible
      effects of contraceptive management of wildlife must also recognise all
      alternative management approaches and apply the same concern and questions to
      these alternative approaches--including 'no management'--as are currently being
      applied to fertility control. Only then will the stewards of wildlife be in a
      position to make wise and informed decisions about management options.

PMID- 17524298
TI  - Effects of aroclor 1254 on the expression of the KAP3 gene and reproductive
      function in rats.
AB  - The present study investigated the effects of aroclor 1254 (A1254) on the
      expression of the kinesin superfamily associated protein 3 (KAP3) gene in F1 rat
      brain during brain sexual differentiation and puberty. In addition, the effects
      of A1254 on reproductive function were examined. The KAP3 gene is involved in the
      neurogenesis and synaptogenesis of sexual differentiation in rats and also during
      puberty. In the present study, pregnant Sprague-Dawley rats each received a daily
      dose of A1254 (0, 10, 50 mg kg(-1)) dissolved in 1.0 mL corn oil by gavage, from
      gestational Day (GD) 8 to postnatal Day (PD) 21. The mRNA levels of the KAP3 gene
      in hypothalamic tissues were analysed by northern blot hybridisation during the
      critical periods of brain sexual differentiation (GD18 and PD5) and puberty
      (PD28). Variables affecting reproduction in F1 female rats, such as vaginal
      opening (VO), vaginal oestrus (VE) and oestrous cyclicity, were recorded.
      Depending on the sex and A1254 exposure (control or 50 mg kg(-1) day(-1)), F1
      rats were divided into three mating groups, namely control male-control female,
      control male-A1254-treated female and A1254-treated male-control female. During
      the critical periods of brain sexual differentiation (GD18, PD5) and puberty
      (PD28), KAP3 mRNA levels were significantly reduced in A1254-treated fetal and
      pubertal rat brains relative to those of control groups. In A1254-treated F1
      female rats, VO and VE were delayed, the percentage of irregular oestrous cycles
      was increased and the duration of the oestrous cycle was extended in a dose
      dependent manner compared with control groups. Treatment with a high dose of
      A1254 significantly impaired the reproductive function of both male and female F1
      rats, including mating and pregnancy indices and the number of live fetuses.
      These data suggest that A1254 disrupts transcriptional regulation of the KAP3
      gene in fetal and pubertal rat brains and that these effects may be related to
      A1254-induced abnormal brain sexual differentiation and lowered reproductive
      function in F1 rats.

PMID- 17524300
TI  - Effects of cobalt/vitamin B12 status in ewes on ovum development and lamb
      viability at birth.
AB  - Scottish Blackface ewes from cobalt-deficient farmland were fed a diet containing
      0.06 mg cobalt per kg dry matter from approximately 30 days before embryo
      recovery/transfer until lambing. Ewes remained untreated (-Co; n = 82) or were
      given an intraruminal cobalt-containing bolus to compensate for the dietary
      deficit (+Co; n = 82). Ewes used as embryo donors (-Co, n = 17; +Co, n = 16) were
      artificially inseminated with semen from a single Suffolk sire. Day 6 embryos
      obtained from -Co and +Co donors were transferred in singleton to -Co and +Co
      recipients in a 2 x 2 factorial-designed experiment to determine the effects of
      cobalt/vitamin B12 status during the periconception period (factor 1) and
      pregnancy (factor 2) on lamb viability at birth. Mean (+/- s.e.m.) circulating
      concentrations of vitamin B12 in -Co and +Co donors at ovum recovery were 182 +/-
      10 and 1288 +/- 64 pmol L(-1), respectively (P < 0.001), and the number of
      corpora lutea per ewe ovulating was 9.9 +/- 1.6 and 14.4 +/- 1.3, respectively (P
      < 0.05). Treatment did not affect the proportion of recovered ova that contained
      >32 cells (viable) or the median stage of development (late morula), but viable
      ova recovered from -Co v. +Co ewes had a better morphological grade (2.0 +/- 0.1
      v. 2.20 +/- 0.04, respectively; P < 0.01). There was no effect of treatment on
      the proportion of recipient ewes that became pregnant. Circulating concentrations
      of vitamin B12 were lower in -Co than +Co ewes during pregnancy (P < 0.001) and
      at birth in lambs born to -Co ewes compared with those born to +Co ewes (P <
      0.001). There was no effect of donor or recipient cobalt/vitamin B12 status on
      lamb birthweight, neonatal vigour or neonatal rectal temperatures, but lambs
      derived from +Co v. -Co embryo donors were more active in the first 3 days after
      birth (P < 0.05). Results show that sub-clinical cobalt/vitamin B12 deficiency
      reduces ovulatory response in superovulated ewes and that periconception
      nutrition can affect neonatal lamb behaviour.

PMID- 17524301
TI  - Neutral alpha-glucosidase activity in mouse: a marker of epididymal function?
AB  - Neutral alpha-glucosidase (NAG) activity is considered a functional epididymal
      marker in several species. Unlike the rat, no NAG activity has been detected in
      mice. The aims of the present study were to evaluate NAG secretory activity (the
      supernatant of the incubated tissue) in mouse epididymis and to determine whether
      it could be used as a functional epididymal marker. Epididymides (whole or in
      parts) were incubated in the presence or absence of testosterone (10(-5) m) and
      secretory NAG activity was compared with known positive controls. Furthermore, we
      compared enzyme activity in epididymides from well-fed and undernourished mice
      (50% food restriction for 21 days), a model that alters the epididymal maturation
      processes. Spectrophotometric analysis revealed NAG activity in mouse epididymis
      (22.6 +/- 3.7 mU g(-1) tissue; n = 4), being higher in the caput. NAG activity
      was statistically higher in the caput than in the corpus and in the cauda. No
      significant differences existed between the caput NAG activity and complete
      epididymis NAG activity. In undernourished mice, we confirmed changes in
      epididymal maturation observed previously (i.e. increased number of immature
      spermatozoa and diminution of the sperm concentration). Concordantly, the
      epididymides of undernourished mice exhibited decreased enzyme secretory
      activity, which increased to values similar to those seen in controls following
      incubation in the presence of testosterone (22.5 +/- 2.6, 12.5 +/- 1.0 and 22.4
      +/- 3.7 mU g(-1) tissue, n = 9 in control (n = 7), undernourished (n = 9) and
      undernourished + testosterone groups (n = 9), respectively). In conclusion, NAG
      activity was detected in mouse epididymis. Although the present study supports
      the possibility of using NAG as an epididymal marker, more studies are necessary
      to effectively prove that NAG activity can be used as an epididymal marker.

PMID- 17524302
TI  - Seasonal variation and circadian rhythmicity of the prolactin profile during the
      summer months in repeat-breeding Murrah buffalo heifers.
AB  - The present study was undertaken to determine a detailed endocrine profile for
      prolactin and progesterone during the oestrous cycle in repeat-breeding Murrah
      buffalo heifers during summer and winter. Hormone concentrations were quantified
      in blood plasma samples collected over the oestrous cycle in both winter and
      summer, as well as in samples collected during the summer months to observe
      circadian rhythmicity. The mean plasma prolactin concentration during the winter
      months ranged from 3.10 +/- 0.48 to 9.17 +/- 1.39 ng mL(-1); during the summer
      months, plasma prolactin concentrations ranged from 248.50 +/- 16.03 to 369.63 +/
      25.13 ng mL(-1). During the winter months, the mean plasma progesterone
      concentration ranged from 0.20 +/- 0.00 to 3.04 +/- 0.34 ng mL(-1), which was
      significantly higher (P < 0.01) than the prolactin concentrations recorded in the
      summer months (range 0.20 +/- 0.00 to 1.48 +/- 0.13 ng mL(-1)). Plasma prolactin
      and progesterone concentrations were negatively correlated (r = -0.24) during the
      summer oestrous cycle, which indicates prolactin-induced suppression of
      progesterone secretion through poor luteal development. During the summer, a
      circadian rhythmicity was observed in buffaloes and the results indicate that
      high prolactin secretion contributes to poor fertility by lowering gonadal
      hormone (progesterone) secretion. It was concluded from the present study that
      prolactin and progesterone profiles during the summer and winter months are
      directly correlated with the reproductive performance of buffaloes. The finding
      also validates the hypothesis that hyperprolactinaemia may cause
      acyclicity/infertility in buffaloes during the summer months due to severe heat
      stress.

PMID- 17524303
TI  - Isolation, culture and characterisation of somatic cells derived from semen and
      milk of endangered sheep and eland antelope.
AB  - Semen and milk are potential sources of somatic cells for genome banks. In the
      present study, we cultured and characterised cells from: (1) cooled sheep milk;
      (2) fresh, cooled and frozen-thawed semen from Gulf Coast native (GCN) sheep
      (Ovis aries); and (3) fresh eland (Taurotragus oryx) semen. Cells attached to the
      culture surface from fresh (29%), cooled (43%) and slow-frozen (1 degrees C/min;
      14%) ram semen, whereas no attachment occurred in the fast-frozen (10 degrees
      C/min) group. Proliferation occurred in fresh (50%) and cooled (100%) groups, but
      no cells proliferated after passage 1 (P1). Eland semen yielded cell lines (100%)
      that were cryopreserved at P1. In samples from GCN and cross-bred milk, cell
      attachment (83% and 95%, respectively) and proliferation (60% and 37%,
      respectively) were observed. Immunocytochemical detection of cytokeratin
      indicated an epithelial origin of semen-derived cells, whereas milk yielded
      either fibroblasts, epithelial or a mixture of cell types. Deoxyribonucleic acid
      microsatellite analysis using cattle-derived markers confirmed that eland cells
      were from the semen donor. Eland epithelial cells were transferred into eland
      oocytes and 12 (71%), six (35%) and two (12%) embryos cleaved and developed to
      morulae or blastocyst stages, respectively. In conclusion, we have developed a
      technique for obtaining somatic cells from semen. We have also demonstrated that
      semen-derived cells can serve as karyoplast donors for nuclear transfer.

PMID- 17524304
TI  - Granulocyte-macrophage colony stimulating factor and interleukin-8 in the
      reproductive tract of ewes following oestrus and mating.
AB  - Cytokines produced in the female reproductive tract after mating may enhance
      reproductive success. The present study investigated the distribution of
      granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-8
      in tissues and luminal secretions from different sites in the reproductive tract
      of the ewe following oestrus and after natural mating. Fifteen ewes were mated
      with a ram for 1 h and their reproductive tracts collected 3, 6, 18, 24 or 48 h
      later. Another 15 ewes were used as oestrous controls. Luminal secretions and
      tissue samples were collected from seven sites in each reproductive tract.
      Secretions were analysed by enzyme-linked immunosorbent assay and tissues were
      stained immunohistochemically using anti-sheep GM-CSF and anti-sheep IL-8
      antibodies. Both cytokines were found in luminal and glandular endometrial
      epithelium and, to a lesser extent, in cervical epithelium; neither was found in
      the vaginal epithelium. Twice as many (P < 0.05) luminal samples from mated ewes
      than non-mated ewes were positive for GM-CSF. The vaginal lumen contained
      significantly higher (P < 0.01) concentrations of IL-8 compared with other sites,
      irrespective of mating status. Significant differences (P < 0.05) were found in
      staining intensity of GM-CSF and IL-8 from different sites. Production of GM-CSF
      and IL-8 by reproductive tissues is likely to contribute to leucocyte
      infiltration into the ovine reproductive tract.

PMID- 17524305
TI  - Optimisation of handling, activation and assessment procedures for Bufo marinus
      spermatozoa.
AB  - In the present study, we investigated handling, activation and assessment
      procedures for cane toad (Bufo marinus) spermatozoa. Optimisation of these
      techniques will facilitate the maintenance of sperm viability during
      cryopreservation and during in vitro fertilisation (IVF) techniques in
      reproduction technologies for endangered species. Spermatozoa were taken from
      testicular macerates and assessed using plasma membrane integrity assays
      (live/dead stains) and quantitative scores of motility parameters. In the
      assessment of sperm viability using live/dead stains, there were small but
      significant differences in the percentage of sperm from cryopreserved samples
      staining positive with propidium iodide, Hoechst H33258 and Trypan blue; these
      differences were not large and all stains performed acceptably. Spermatozoa were
      activated by dilution of testicular macerates in water at one of two dilution
      ratios (1 : 6 or 1 : 20) with or without 0.1-5.0 mM theophylline. Sperm plasma
      membrane integrity (unstained spermatozoa) was unaffected by either dilution
      ratio (osmolarity) or theophylline concentration. However, sperm motility was
      significantly affected by osmolarity and theophylline concentration. The
      stimulation of sperm motility increased with higher theophylline concentrations
      and these strongly interacted with lower osmolarities through a higher dilution
      ratio of sperm macerates with water. Spermatozoa were exposed to increasing
      centrifugation forces to determine tolerance to physical stresses encountered
      during washing procedures. Forces between 50 and 800 g were associated with a
      significant reduction in motility (mean 56 +/- 3% decreasing to 27 +/- 3%), but
      did not affect staining. In conclusion, centrifugation should be minimised in
      anuran sperm washing procedures; osmotic shock associated with higher dilution
      ratios reduces the capacity of anuran sperm to achieve high percentages of motile
      sperm, leading to a likely trade-off between dilution required for activation and
      sperm motility to optimise IVF fertilisation rates; and optimal conditions for
      sperm motility after activation occur at lower dilutions of suspensions with 5.0
      mM theophylline. The present study has improved protocols for the handling of
      anuran sperm during pre- and post-cryopreservation procedures.

PMID- 17524306
TI  - [Sentinel node in breast cancer and gynecologic tumors: present, and future?].

PMID- 17524307
TI  - [Patients treated for differentiated thyroid cancer with negative 131I whole-body
      scans and elevated thyroglobulin levels: a possible course].
AB  - OBJECTIVE: To verify the existence of patients with treated differentiated
      thyroid cancer (DTC) with negative 131I whole-body scanning (WBS) and high serum
      thyroglobulin (Tg) in the follow-up who evolve towards normalization without
      other therapy interventions. MATERIAL AND METHODS: Retrospective revision of the
      periodic examinations established in the protocol for patients with DTC,
      analyzing the levels of Tg found with IRMA annually in those with hormonal
      treatment and every 1-5 years in absence of previous hormonal treatment to WBS.
      Minimum surveillance of 2 years. Those who had elevated levels of Tg and WBS and
      other negative imaging tests in their course were selected. The characteristics
      of the patients selected were analysed in those whose Tg levels evolved to
      normalization without specific medical or surgical treatment (Group I) and those
      who did not reach normalization of Tg (Group II). RESULTS: A total of 130
      patients (17.93 %) with high levels of Tg and negative WBS were detected. Group
      I: 31 patients (4.28 %), 11 men and 20 women; average age at the moment of the
      diagnosis of 33.4 years (rank: 5-60); average surveillance: 12.4 years (+/- 7.4).
      HISTOLOGY: 27 papillary and 4 follicular carcinoma. Average ablation dose: 3.260
      GBq (88,1 mCi); average total I131 dose: 6.850 GBq (185.13 mCi). Tg normalization
      average time: 8.2 years. Group II: 99 patients (13.65 %), 27 men and 72 women.
      Average age of 40.4 years (rank: 7-76). Average surveillance: 9.8 years.
      HISTOLOGY: 86 papillary and 13 follicular carcinoma. Average ablation dose: 3.266
      GBq (88.28 mCi); average total 131I dose: 9.363 GBq (253,06 mCi). Two of the
      patients in group I had negative PET-FDG. There were 13 patients in whom
      progressive reduction of the levels of thyroglobulin without reaching
      normalization with negative PET-FDG was detected. CONCLUSIONS: In patients with
      radiated DTC, deferred normalization of the levels of the serum thyroglobulin is
      possible. Empirical treatments cannot be considered the only factor that
      contributes to this result, which can occur without the administration of high
      doses of 131I.

PMID- 17524308
TI  - [Patient satisfaction as quality indicator in a nuclear medicine department].
AB  - OBJECTIVE: To assess patient satisfaction and dissatisfaction with a Nuclear
      Medicine department. MATERIAL AND METHODS: A questionnaire was designed with 9
      closed questions, 1 with a numerical scale (1-10) and 1 with an open question for
      suggestions. The questions included different quality dimensions of the
      department related with waiting time for the scan, information, facilities,
      attention manner with department staff and global satisfaction (numerical scale,
      1-10). Dissatisfaction was determined by analyzing the written complaints for the
      last 6 years. RESULTS: A total of 671 questionnaires were obtained, 58 % of those
      surveyed being women. The mean age of patients was 56.5 (+/- 16.26). The
      information provided was correct in 81.7 % of cases. Equipment and facilities
      were correct for 74.5 % of patients. Waiting list and waiting time were correct
      for 70 % and 66.4 % respectively. The attention manner of the department staff
      was the most satisfactory dimension (98.7 %). Global satisfaction was positive (>
      or = 7 out of 10) in 82.8 % of the patients. 29 complaints were received. Most of
      them were based on waiting list (12) and disagreement with assistance (9).
      CONCLUSIONS: Global satisfaction was high in most of patients. Waiting time was
      the dimension with the lowest level of satisfaction and subsidiary of improvement
      plans. The primary spontaneous complain by our patients was due to the waiting
      list.

PMID- 17524309
TI  - [Scintimammography with 99mTC-MIBI in the clinical practice: repercussion on the
      clinical management of the patient].
AB  - OBJECTIVE: Establish the usefulness of scintimammography (SM) in day-to-day
      clinical practice. MATERIAL AND METHODS: We have evaluated 308 SM consecutively
      performed in our Department. The diagnosis was established by way of biopsy or
      clinical and mammography follow-up (minimum 18 months). In all cases we evaluated
      the kind of lesions (palpable or non-palpable) and their degree of suspicion of
      malignancy in the mammography (BIRADS). We determined the number of fine-needle
      aspiration cytology (FNAC) or biopsies performed in dependence of kind of
      lesions, mammography and SM results. RESULTS: Final diagnosis was cancer in 18 %
      of the patients, and 71 % of the lesions were non palpable. Negative predictive
      value (NPV) of SM was 96 %. Pathological diagnosis was performed in 100 % of
      lesions with SM+ and 16 % of lesions with SM-. According to the kind of lesion,
      FNAC and/or biopsy was performed in 62 % of palpable lesions and in 20 % of non
      palpable lesions; and according to the mammography in 21 % of lesions BIRADS I
      II, 14 % in BIRADS III, 70 % in BIRADS IV and 100 % in BIRADS V. The number of
      FNAC and/or biopsies performed is significantly higher in all cases when SM is
      positive (p > 0,001), excepting in BIRADS V lesions. CONCLUSIONS: In day-to-day
      clinical practice SM is generally performed in low prevalence of breast cancer
      population, in the evaluation of non-palpable lesions with a low suspicion of
      malignancy. SM has a high NPV, increase the diagnostic accuracy of the
      mammography and has repercussion on patient management, except in BIRADS V
      lesions.

PMID- 17524310
TI  - Non-resected solid papillary epithelial tumor of the pancreas: 18F-FDG PET/CT
      evaluation at 5 years after diagnosis.
AB  - Solid and papillary epithelial neoplasm of the pancreas (SPEN) is an
      encapsulated, slowly enlarging abdominal mass that generally shows no evidence of
      capsular invasion, regional lymph node involvement, or distal metastases. We
      present a 68 years old Hispanic male diagnosed with SPEN 5 years earlier that
      refused surgical excision. Presently he underwent a whole-body 18F-FDG PET/CT.
      Although tumor size, location and CT features did not seem to depict significant
      changes, FDG-PET was useful showing persistent tumoral activity. A brief review
      of the differential diagnosis as well as the usefulness of FDG-PET in SPEN (a
      slow growing pancreatic neoplasm) is presented.

PMID- 17524311
TI  - [Evolution in 18F-FDG-PET of a case of Hodgkin disease, nodular sclerosis
      variety, after treatment and autotrasplant].
AB  - Positron Emission Tomography (PET) has become a very useful tool for monitoring
      Hodgkin's disease patients in the last years. When there is suspicion of disease
      persistence after treatment, this technique makes it possible to evaluate
      treatment activity of the residual lesions observed in the CT scan. Furthermore,
      due to the whole body study, new tumor sites, which very often change the
      therapeutic option, can be detected. We must take into account, however, that 18F
      FDG is a very sensitive but not very specific tumor marker, since some
      inflammatory or infectious conditions may be associated to significant
      radiopharmaceutical uptakes. Thus, in order to increase specificity it is
      mandatory to correlate the PET information with the rest of the conventional
      imaging and clinical data and evolution of the patient. We present the case of a
      woman with Hodgkin's disease in which 18F-FDG PET was included in the follow-up.
      Both conditions, tumor and infection, were present in different times of the
      course. The integration of all the x-ray, clinical, laboratory and metabolic
      information allowed for a better and correct management of this patient.

PMID- 17524312
TI  - [Study of somatostatin receptors in post-surgical mesenteric mass].

PMID- 17524313
TI  - [Pubis osteomyelitis in adolescent as cause of fever with unknown focus].

PMID- 17524314
TI  - [Some frequently used terms in nuclear medicine].

PMID- 17524315
TI  - [Consensus meeting on selective biopsy of the sentinel node in breast cancer.
      Spanish Society of Senology and Breast Disease].
AB  - Selective biopsy of the sentinel node is a useful diagnostic technique in the
      management of breast cancer that has been introduced into the clinical practice
      and is widely used and accepted. Based on its results, adequate staging can be
      made with less associated morbidity. However, at present, there are many
      methodological variations in how it is done that are pending to be answered in on
      going trials and investigations. This involves making Consensus Meetings to try
      to homogenize the aspects related with the method and indication of the
      technique. The conclusions of the Consensus Meeting held in Murcia and organized
      by The Spanish Society of Senology and Breast Disease are expressed in this
      document.

PMID- 17524316
TI  - [Predictive value of lipoprotein (a) and apolipoprotein A1 in patients with
      angiographycally evaluated coronary stenosis].
AB  - BACKGROUND AND OBJECTIVE: To examine the relationship between blood levels of
      lipids, hemostatic and inflammatory markers and the presence of angiographycally
      evaluated coronary stenosis. PATIENTS AND METHOD: We included 397 consecutive
      patients (267 males and 130 females) who were admitted to the hospital because of
      an acute episode of chest pain. Each patient underwent a coronariography using
      the Seldinger technique. A blood sample was drawn to analyze lipids -total
      cholesterol, high density lipoproteins-cholesterol (HDLc), triglycerides, low
      density lipoproteins-cholesterol (LDLc), apolipoprotein A1, apolipoprotein B100,
      lipoprotein (a)-, hemostatic (fibrinogen, D-dimmer), and inflammatory (C-reactive
      protein, leukocyte count) markers. To evaluate the differences between mean
      values of quantitative variables, the Student's t-test was used for parametric
      variables and the Mann Whitney U test for non-parametric variables. Categorical
      variables were compared using the chi-square test. A logistic regression analysis
      was employed to determine the influence of high levels of the studied parameters
      on the presence of coronary obstruction. RESULTS: 295 patients had coronary
      stenosis (group 1) and 102 had not a significant obstruction (group 2). Patients
      with coronary stenosis had higher values of lipoprotein (a), D-dimmer, C-reactive
      protein and leukocyte count and lower HDLc, apolipoprotein A1 and total
      cholesterol. When markers were dichotomized in high values (fourth quartile) and
      low (first-third quartile), high lipoprotein (a) (odds ratio [OR] = 2.508; 95%
      confidence interval [CI], 1.222-5.145) and apolipoprotein A1 levels (OR = 0.472;
      95% CI, 0.267-0.837) were significant using the multivariate logistic regression
      model adjusted sex, tobacco and age. CONCLUSIONS: Among patients undergoing
      coronary angiography, high lipoprotein (a) levels are independently associated
      with the presence of coronary obstruction whereas high apolipoprotein A1 values
      show a protective effect.

PMID- 17524317
TI  - [Relation between changes in retinal microcirculation and other organ damage in
      hypertension and regression with antihypertensive treatment].
AB  - BACKGROUND AND OBJECTIVE: The possibility to aplicate a semi-automatic
      computerized system to evaluate the calibre of retinal blood vessels, has shown
      very good reproducibility, and have let us measure the calibres of retinal
      arterioles and veins, and their ratio (AVR). PATIENTS AND METHOD: We have
      measured the calibres of retinal vessels in a group of 51 hypertensive
      outpatients before and after 6 months' treatment with losartan or, losartan plus
      hydrochlorothiazide if the association was required to adequate control of the
      blood pressure. RESULTS: AVR increased from 0.7530 (0.03) to 0.7563 (0.03) (p =
      0.005). We have related these modifications with damage in other target organs
      and we have found out a inverse relation between AVR and left ventricular mass
      index. This relation could be confirmed in multiple regression analysis. We have
      found no relation between AVR and microalbuminuria, probably because of its
      variability. CONCLUSIONS: These results suggest a relation between retinal
      microcirculation and hypertensive cardiopathy, but they should be interpreted
      with caution because the sample is small.

PMID- 17524318
TI  - [Folic acid dose in the prevention of congenital defects].
AB  - BACKGROUND AND OBJECTIVE: Synthetic folic acid (FA) is in the form of
      pteroylmonoglutamate (PGA), a form that does not occur in nature, where it is in
      form of pteroylpolyglutamate, mainly as 5-methyltetrahydrofolate. The organism
      transforms PGA into 5-methyltetrahydrofolate, and it has been detected that this
      process is saturated at doses of 0.4 mg of PGA. Recently, some concern has been
      expressed on the use of higher than recommended doses of FA, because of the
      possibility of saturating the biotransformation process and the consequent
      plasmatic accumulation of unmetabolized synthetic FA. The objective of this study
      is to analyze the doses of synthetic FA that are being currently used in Spain,
      as well as its secular and geographic distribution. PATIENTS AND METHODS: The
      study was based on 16,761 mothers of non-malformed infants from the data base of
      the Spanish Collaborative Study of Congenital Malformations. All forms of folates
      (folic or folinic) have been considered under the general term of FA. RESULTS:
      Although an increasing trend in the proportion of mothers using FA in the last
      study period (2003-2004), only 17.37% of the mothers had FA supplements since
      before pregnancy. Among the rest, 71.13% started using FA once they knew they
      were pregnant, and 11.50% never took this vitamin. In addition, more than 70% of
      mothers who took FA ingested doses of 4 mg or more. The results by Spanish
      Autonomic Regions are quite similar, with more that 50% of the mothers (of the
      period 2003-2004), in the great majority of the Regions, taking mean daily doses
      of FA that are between 12.5 and 20-fold higher than the recommended 0.4 mg/day.
      CONCLUSIONS: Most of women are having FA after conception, or do not ingest FA at
      all. Most of those women who take FA use doses much higher than recommended. The
      results of this study show that it is necessary to spread these aspects among the
      health professionals implicated.

PMID- 17524319
TI  - [Serum markers of coronary atherosclerosis].

PMID- 17524320
TI  - [Validity of Freud's psychoanalysis].

PMID- 17524321
TI  - [Obesity of health shift workers from the Canary Islands, Spain].

PMID- 17524322
TI  - [Diabetes mellitus in children: a heterogeneous disease].
AB  - Diabetes is one of the most common chronic diseases of childhood and adolescence.
      Type 1, or autoimmune diabetes accounts for more than 95% of cases. Nevertheless,
      over the past years it has become apparent that not all cases of diabetes
      presenting in children are autoimmune type 1. In these cases, the diagnosis is
      facilitated by the fact that many rare etiologies of diabetes are associated with
      specific clinical syndromes or a characteristic age of onset. In addition,
      molecular diagnosis is becoming increasingly available for several of these
      disorders. This review aims to provide the general physician with some important
      clues to make an accurate diagnosis in these patients and understand its
      implication in clinical management.

PMID- 17524323
TI  - [Primary health care research as source of knowledge].

PMID- 17524324
TI  - [Fulminant hepatic failure due to herpes simplex virus in a non-immunesuppressed
      adult patient].

PMID- 17524325
TI  - [Blastocystis hominis infection and diarrhoea].

PMID- 17524326
TI  - [Castleman's disease of the subcutis].

PMID- 17524327
TI  - [Tonsilar abscess due to Actinomyces spp].

PMID- 17524328
TI  - [Where do X-rays come from?].

PMID- 17524329
TI  - [Case imaging: 1. Penile calciphylaxis].

PMID- 17524330
TI  - [A review of the scientific evidence concerning the clinical application of
      digital mammography].
AB  - OBJECTIVE: To review the scientific evidence with respect to the use of digital
      mammography and compare it with analogical mammography in the clinical context.
      MATERIAL AND METHOD: We searched Medline and EMbase for studies published between
      1989 and 2005 that compared the results of digital and analogical mammography in
      the same group of patients or in two different groups of patients to evaluate
      their respective diagnostic accuracy (sensitivity, specificity, area under the
      ROC curve), recall rate, biopsy rate, and exposure to radiation. We reviewed and
      compared the different methodologies of the studies published. RESULTS: Eight
      articles and eight presentations at congresses were found. No statistically
      significant differences were observed between digital and analogical mammography
      for the detection of breast cancer. Until the publication of the Oslo II (2004)
      and Digital Mammographic Imaging Screening Trial (2005) studies, the series
      presented were small and used a variety of methodologies. This made it impossible
      to appreciate small differences in diagnostic accuracy between the two techniques
      and to group the, sometimes, contradictory results. Furthermore, these first
      series did not include follow-up. CONCLUSION: There are no statistically
      significant differences between the two techniques for diagnostic accuracy,
      except in women with dense or heterogeneously dense breasts, in those under 50
      years of age, and in peri- or pre-menopausal women, in which cases digital
      mammography is significantly better. These data should be confirmed in longer
      term studies to enable the effects on the breast cancer mortality rate to be
      specifically evaluated. Cost-effectiveness studies are important when considering
      changing techniques.

PMID- 17524331
TI  - [Diagnostic imaging techniques for analyzing heart function: indications and
      limitations].
AB  - Cardiac function analysis is critical in the management of patients with
      cardiovascular diseases. The two most common non-invasive techniques used
      nowadays to evaluate cardiac function are ultrasonography and magnetic resonance
      imaging (MR). The parameters to be determined with both techniques include the
      systolic volume of the left ventricle, the cardiac mass, myocardial thickness and
      ejection fraction. Ultrasound images have high resolution and they do not need
      any cardiac or respiratory gating. It has limitations in obese patients, patients
      with pulmonary obstructive disease or patients after thoracic surgery. MR has a
      high spatial and temporal resolution. There are different sequences we can use to
      determine cardiac function parameters, Gradient Echo sequences are used to
      analyze the ventricular volume and the ejection fraction. Myocardial tagging
      sequences are used to quantify the myocardial wall motion. Computed Tomography
      constitutes other alternative that can be used in patients with claustrophobia or
      pace markers to evaluate cardiac function.

PMID- 17524332
TI  - [Ultrasonography of the tendons: from image to pathology].
AB  - Radiology allows to define etiologies of tendon injuries and authorize a most
      suitable treatment. For that reason, the use of the sonography has been developed
      from several years and has four main purposes to define the type of injury and to
      orient the treatment: to confirm the real existence of the tendon tear, to need
      the exact location the same one, to determine the gravity of the lesion, and
      finally, to evaluate its acute or chronic character. In this paper, we will try
      to define the normal pattern of the tendon and describe the more frequent lesions
      of the shoulder or the ankle: complete or partial tear, tendinopathy, dislocation
      and enthesopathy.

PMID- 17524333
TI  - [Case imaging: 2. Ovarian vein thrombophlebitis].

PMID- 17524334
TI  - [Magnetic resonance diagnosis of ankylosing spondylitis and evaluation of the
      response to treatment].
AB  - OBJECTIVE: To show the role of magnetic resonance imaging in the early diagnosis
      of ankylosing spondylitis and discuss its possible usefulness in evaluating the
      response to treatment. MATERIAL AND METHODS: We describe the findings on magnetic
      resonance images using STIR and contrast-enhanced T1-weighted sequences in 13
      patients diagnosed with ankylosing spondylitis receiving adalimumab treatment.
      Magnetic resonance images were acquired at baseline and after six months. We
      describe the findings obtained and the results of the quantitative analysis of
      vertebral affection (using the ASspiMRI-a score), and sacroiliac and hip joint
      affection. RESULTS: Inflammatory effects were demonstrated in 12 patients as
      signal hyperintensity in STIR sequences and as contrast enhancement in T1
      weighted sequences. After treatment, 12 patients showed decreased ASspiMRI-a
      score and less affection in the sacroiliac and hip joints. No changes were
      observed in the remaining patient. Two patients showed posterior vertebral
      element involvement and disc involvement was seen in three. CONCLUSIONS: MRI
      opens up new possibilities for the management of patients with ankylosing
      spondylitis. On the one hand, it enables early diagnosis, saving the patient
      years of trial treatments and saving the healthcare system the cost of multiple
      diagnostic tests to try to explain the symptoms these patients present. On the
      other hand, it enables the rapid, objective evaluation of the response to
      therapy, thus making it possible to step up to a new, more aggressive therapy
      quickly and avoid treatments that are not very effective.

PMID- 17524335
TI  - [Case imaging: 3. Mediastinic liposarcoma].

PMID- 17524336
TI  - [Doppler ultrasonography of scrotal injury].
AB  - OBJECTIVES: To review the current body of knowledge about performing,
      understanding, and interpreting Doppler ultrasonography in scrotal injury.
      MATERIAL AND METHODS: 17 patients with scrotal injury were studied. We describe
      the ultrasound technique and a wide spectrum of traumatic pathology together with
      its complications, analyzing the ultrasonographic signs and Doppler flow patterns
      that can orient the diagnosis and approach to treatment. RESULTS: The most common
      posttraumatic lesions were epididymo-orchitis and (26%) and scrotal hematomas
      (25%). The most frequent complications were testicular ischemia (3 cases) and
      abscess formation (2 cases). The surgical emergencies were torsion (8%) and
      testicular rupture (8%). CONCLUSIONS: Scrotal injuries can cause lesions that
      vary widely in severity, semiotics, and treatment. Doppler ultrasonography is an
      accurate tool in the hands of an experienced radiologist, enabling a clear,
      accurate diagnosis to be reached reasonably fast in pressing circumstances.

PMID- 17524337
TI  - [Case imaging: 4. Lithium nephropathy].

PMID- 17524338
TI  - [Radiological characteristics of malignant fibrous histiocytoma of bone].
AB  - Malignant fibrous histiocytoma (MFH) was only recognized as a primary bone tumor
      a few years ago. Although it is much rarer than malignant fibrous histiocytoma of
      soft tissues, it is not extremely uncommon. It predominantly affects long bones;
      however, it has been reported to occur in many different sites and at any age.
      MFH are aggressive tumors that can appear in association with other bone lesions,
      and they have a poor prognosis. We present our experience with 13 cases of MFH
      and review the literature to describe the main characteristics of this tumor.

PMID- 17524339
TI  - [Sarcoidosis with systemic involvement: a report of two cases].
AB  - Sarcoidosis is a multisystemic granulomatose disease of unknown origin that most
      often affects the lung parenchyma and the mediastinal lymph nodes. Although less
      common, involvement of the abdominal organs and the central nervous is also
      possible. We present the radiological findings observed in two patients diagnosed
      with sarcoidosis with systemic involvement. In one case, the disease affected the
      lung, spleen, mediastinal and abdominal lymph nodes, whereas in the other case it
      affected the lung, spleen, abdominal lymph nodes and central nervous system. The
      aim of this report is to review the radiologic manifestations of this disease.

PMID- 17524340
TI  - [Case study of puncturing thoracic injury with right ventricle perforation and
      cardiac tamponade].
AB  - We present a case of open thoracic traumatism with heart wound and pericardial
      tamponade. The echocardiographic findings were inconclusive and contrast-enhanced
      computed tomography (CT) with fine reconstructions was performed. We discuss the
      role of CT with emphasis on the radiological signs related to myocardial
      perforation, hematic pericardial effusion, and cardiac tamponade, as well as
      ruling out other associated lesions. CT was useful in the evaluation of
      hemodynamically stable patients with open cardiac wounds and inconclusive
      echocardiographic findings.

PMID- 17524341
TI  - [Well-differentiated basal cell adenocarcinoma of the lacrimal sac: a case
      report].
AB  - Basal cell adenocarcinoma is a rare tumor first considered to be a separate
      entity by the WHO in 1991. The mean age of presentation is 48 years and it does
      not affect one gender more than the other. It normally follows an insidious
      course with nonspecific signs and symptoms. We present a case of adenocarcinoma
      of the lacrimal sac diagnosed at histological study. We show the CT, MRI, and
      histological findings. We discuss the differential diagnosis and treatment for
      this tumor.

PMID- 17524342
TI  - [Desmoplastic fibroma of bone: a report of two cases].
AB  - Desmoplastic fibroma is a rare bone tumor with benign, locally aggressive, lytic
      behavior. Histologically, it is very similar to the more common and better known
      desmoid tumor. It can occur at any site in the skeleton but is most common in the
      mandible or in the long bones. We present two cases; the tumor was located in the
      proximal tip of the fibula in one case and in the proximal tip of the femur in
      the other. We describe the appearance of these lesions on CT and MRI. In both
      cases, the lesions were lytic, expansive, with a trabeculated appearance and
      internal septa, and without mineralized osseous matrix. At MRI, one of the tumors
      was very heterogeneous, with two differentiated areas on T2-weighted sequences:
      the upper zone was hypointense and the lower zone showed intermediate signal
      intensity. We also describe the behavior of the tumor after the administration of
      intravenous Gadolinium: the upper zone showed no significant enhancement and the
      lower showed significant enhancement in the early phase.

PMID- 17524343
TI  - [Heterotaxy syndrome (polysplenia) in an adult].
AB  - We present the case of a 63-year-old woman with heterotaxy syndrome and
      polysplenia who presented with clinical signs and symptoms of recurrent acute
      pancreatitis in which the biliary origin had been seen in the most recent
      episode. This syndrome is rare in adult patients because it is associated with
      congenital heart defects. It is important to know the visceral anomalies that are
      common in this syndrome to avoid confusing them with pathological processes.

PMID- 17524345
TI  - Characterization of a proton pumping transmembrane protein incorporated into a
      supported three-dimensional matrix of proteoliposomes.
AB  - Surface analytical tools have gained interest in the bioanalytical field during
      recent years because they offer the possibility of more detailed investigations
      of biomolecular interactions. To be able to use such tools, the biomolecules of
      interest must be immobilized to a surface in a functioning way. For small water
      soluble biomolecules, the surface immobilization is quite straightforward, but it
      has been shown to be difficult for large transmembrane proteins. In those cases,
      the solid surface often has a negative influence on the function of the
      transmembrane proteins. In this article, we present a new approach for surface
      immobilization of transmembrane proteins where the proteins were immobilized on a
      surface in a proteoliposome multilayer structure. The surface-binding events and
      the structure of the surface-immobilized proteoliposomes were monitored using
      both the quartz crystal microbalance with dissipation monitoring (QCM-D) and
      surface plasmon resonance (SPR) techniques. With this multilayer proteoliposome
      structure, it was possible to detect trypsin digestion of the transmembrane
      protein proton translocating nicotinamide nucleotide transhydrogenase in real
      time using SPR. The results from the combined SPR and QCM-D analysis were
      confirmed by fluorescence microscopy imaging of the multilayer structure and
      activity measurements of transhydrogenase. These results showed that the activity
      of transhydrogenase was significantly decreased in the bottom layer, but in the
      subsequent proteoliposome layers 90% of the activity was retained compared with
      bulk measurements. These results emphasize the importance of an immobilization
      strategy where the transmembrane proteins are lifted off the solid surface at the
      same time as the amount of protein is increased. We consider this new method for
      surface immobilization of transmembrane proteins to meet these demands and that
      the method will improve the possibility to use a variety of surface analytical
      tools for the analysis of interactions involving transmembrane proteins in the
      future.

PMID- 17524346
TI  - [Transapical approach for aortic stented valve implantation: experimental
      results].
AB  - OBJECTIVE: Percutaneous aortic valve replacement has been performed in humans
      mainly for non-surgical candidates. We evaluated on animals a transapical
      approach to deliver an aortic stented valve without cardiopulmonary bypass.
      METHODS: A tubular pericardial valve fixed within a cobalt-nickel stent
      (Medtronic, Inc.) was implanted using a transapical approach in five adult sheep.
      A left thoracotomy was used to access the apex of the heart. The crimped valve
      was deployed in orthotopic position with a valvuloplasty balloon catheter on the
      beating heart after decreasing the left ventricular pressure by using either
      drugs or inferior vena cava occlusion. Deployments were performed under
      fluoroscopy and epicardial 2D Doppler echocardiography. Exact positioning of the
      valve into the target area was confirmed by autopsy at the end of the procedures.
      RESULTS: Valves were unsuccessfully deployed at the target site in all cases but
      one. Three valves were implanted in a supra-annular position with two of them in
      supracoronary position. One valve was implanted below the native annulus in the
      outflow tract. Valvular leak was noted in all but one implants. Coronary
      obstruction occurred twice and early valve retrograde migration once. Ventricular
      fibrillation or diastolic cardiac arrest occurred less than 20 minutes after
      stent deployment in all cases. CONCLUSION: In our experience the transapical
      approach does not facilitate delivery of a stented valve. Despite its technically
      feasibility, advanced stent design and improvements in delivery system are
      required before to continue experimental studies in transapical approach for
      aortic stented valve.

PMID- 17524347
TI  - Etiological diagnosis of hyperprolactinemia.
AB  - There are numerous etiologies of hyperprolactinemia, a common reason for
      consultation. Diagnostic measures must be capable of identifying the tumors, the
      most frequent of which are prolactin adenomas. Hypothalamic-pituitary MRI is the
      reference morphological examination. In clinical practice, it is usually
      performed very early, following the discovery of increased plasma concentrations
      of PRL. This approach is warranted for marked increase in PRL in the absence of
      drugs with hyperprolactinemic effects (>10 x upper limit of normal) since a
      diagnosis of PRL adenoma is extremely likely under such circumstances. When
      hyperprolactinemia is moderate, which is the most common finding in practice, all
      etiologies are possible in theory and it is important to follow a rational
      diagnostic plan (history-taking to identify use of any drugs with
      hyperprolactinemic effects paying attention to renal and hepatic history,
      investigation for endocrine diseases occasionally associated with
      hyperprolactinemia such as hypothyroidism or polycystic ovary syndrome (PCOS),
      confirmation of hyperprolactinemia by a second assay when the initial level is
      less than five times the upper normal limit, pregnancy testing for women of
      childbearing age) in order to rule out all non-tumoral causes of
      hyperprolactinemia before proceeding with imaging. Absence of any consequences of
      hyperprolactinemia on gonadic function or the existence of a concomitant disease
      that could account for the clinical signs, demonstration of wide variations in
      PRL from one assay to another in a single patient could prompt screening for
      macroprolactinemia before MRI is ordered. Macroprolactinoma could also occur in
      the case of normal or doubtful MRI or discrepancy in response to medical or
      surgical treatment. T1- and T2-weighted coronal sections (with or without T1
      after gadolinium injection) are generally sufficient for diagnosis of
      microprolactinoma. Dynamic tests may be useful if MRI is normal or unclear.
      Gadolinium injection with sagittal and axial sections is essential for
      examination of large lesions. In this case, when the increase of PRL is moderate
      (<150 mg/ml), a non-lactotropic lesion may be suspected without misdiagnosing a
      hook effect. Careful analysis of the images allows differentiation between
      tumoral lesions and pituitary hyperplasia.

PMID- 17524348
TI  - Biomechanical evaluation of bike power saver.
AB  - Bike power saver (BPS) is a new product that claims to change the angle of
      pedaling forces and reduce applied power dead range (Chic Sheng Industrial Co.,
      Ltd, Taiwan, China). In order to determine its effectiveness, we quantified how
      BPS operates through a 3D kinematical study and electromyography (EMG) analysis
      of leg muscles during pedaling. Ten kinesiology students participated in this
      study. A 3D motion capture system consisting of nine high-speed cameras (VICON
      v8i, a capture rate of 120 frames/s) was used to collect the total body and pedal
      motion with and without BPS at statically determined low, middle and high
      intensity cycling levels. The short-time test (14s) was applied to all intensity
      levels while the long-time test (30 min) was applied only to the low wattage
      level. Wireless EMG was synchronized with the 3D motion capture system to monitor
      the right and left tibialis anterior, gastrocnemius, quadriceps and hamstring.
      The results revealed that BPS did not alter hip and knee movement significantly
      (p>0.05), but it did vary ankle movement. BPS caused a movement change in the
      pedals, and consequently induced instability in ankle control. The altered pedal
      movement led to an increase in activity level and presumably also energy
      expenditure for dominant muscles, resulting in a faster fatigue process. From
      these data, it is likely that the BPS actually requires more effort than a
      standard bike.

PMID- 17524349
TI  - Ouabain activates signaling pathways associated with cell death in human
      neuroblastoma.
AB  - Cardiotonic steroids (CTS) like ouabain are not only specific inhibitors of the
      sodium pump (Na(+),K(+)-ATPase), they also can influence various cytosolic
      signaling events in a hormone-like manner. In the neuroblastoma cell line SH-SY5Y
      ouabain triggers multiple signaling pathways. Within 30 min of incubation with 1
      or 10 microM ouabain, SH-SY5Y cells generate reactive oxygen species to a level
      approximately 50% above control and show a modest but significant elevation in
      cytosolic [Ca(2+)] of about 25%. After 6 h of exposure, ouabain stimulates a
      series of anti-apoptotic actions in SH-SY5Y cells, including concentration
      dependent phosphorylation of Erk1/2, Akt, and Bad. Nevertheless, at the same time
      this CTS also induces a series of events that inhibit retinoic acid-induced
      neuritogenesis and promote cell death. Both of these latter phenomena are
      possibly associated with the observed ouabain-induced reduction in the abundance
      of the anti-apoptotic proteins Bcl-XL and Bcl-2. In addition, ouabain treatment
      results in cytochrome c release into the cytosol and induces activation of
      caspase 3, events that point towards the stimulation of apoptotic pathways that
      are probably enhanced by the stimulation of p53 phosphorylation at Ser15 also
      observed in this study. These pathways may eventually lead to cell death:
      treatment with 10 nM ouabain results in a 20% decrease in cell number after 4
      days of incubation and treatment with 1 microM ouabain decreases cells number by
      about 75%. The results obtained here emphasize the importance of further research
      in order to elucidate the various signalling cascades triggered by ouabain and
      possibly other CTS that are used in the treatment of heart failure and to
      identify their primary receptor(s).

PMID- 17524351
TI  - Solid-state NMR as a method to reveal structure and membrane-interaction of
      amyloidogenic proteins and peptides.
AB  - It is important to understand the Amyloid fibril formation in view of numerous
      medical and biochemical aspects. Structural determination of amyloid fibril has
      been extensively studied using electron microscopy. Subsequently, solid state NMR
      spectroscopy has been realized to be the most important means to determine not
      only microscopic molecular structure but also macroscopic molecular packing.
      Molecular structure of amyloid fibril was first predicted to be parallel beta
      sheet structure, and subsequently, was further refined for Abeta(1-40) to be
      cross beta-sheet with double layered in register parallel beta-sheet structure by
      using solid state NMR spectroscopy. On the other hand, anti-parallel beta-sheet
      structure has been reported to short fragments of Abeta-amyloid and other amyloid
      forming peptides. Kinetic study of amyloid fibril formation has been studied
      using a variety of methods, and two-step autocatalytic reaction mechanism used to
      explain fibril formation. Recently, stable intermediates or proto-fibrils have
      been observed by electron microscope (EM) images. Some of the intermediates have
      the same microscopic structure as the matured fibril and subsequently change to
      matured fibrils. Another important study on amyloid fibril formation is
      determination of the interaction with lipid membranes, since amyloid peptide are
      cleaved from amyloid precursor proteins in the membrane interface, and it is
      reported that amyloid lipid interaction is related to the cytotoxicity. Finally
      it is discussed how amyloid fibril formation can be inhibited. Firstly, properly
      designed compounds are reported to have inhibition ability of amyloid fibril
      formation by interacting with amyloid peptide. Secondly, it is revealed that site
      directed mutation can inhibit amyloid fibril formation. These inhibitors were
      developed by knowing the fibril structure determined by solid state NMR.

PMID- 17524352
TI  - Conformational behavior of oxygenated mycobacterial mycolic acids from
      Mycobacterium bovis BCG.
AB  - Phase diagrams of Langmuir monolayers of oxygenated mycolic acids, i.e. methoxy
      mycolic acid (MeO-MA), ketomycolic acid (Keto-MA), and artificially obtained
      deoxo-mycolic acid (deoxo-MA) from Mycobacterium bovis BCG were obtained by
      thermodynamic analysis of the surface pressure (pi) vs. average molecular area
      (A) isotherms. At lower temperatures and lower surface pressures, both Keto- and
      MeO-MAs formed rigid condensed monolayers where each MA molecule was considered
      to be in a 4-chain form, in which the three carbon chain segments due to bending
      of the 3-hydroxy aliphatic carboxylate chain and the 2-side chain were in compact
      parallel arrangement. At higher temperatures and surface pressures, MeO-MA and
      deoxo-MA tended to take stretched-out conformations in which the 3-hydroxy
      aliphatic carboxylate chain was more or less in an extended form, but Keto-MA
      retained the original 4-chain structure. The thickness measurement of the
      monolayers in situ by ellipsometry at different pi values and temperatures
      supported the above conclusions derived from the phase diagrams. The enthalpy
      changes associated with the phase transitions of MeO-MA and deoxo-MA implied that
      the MeO-MA needed larger energy to change from a compact conformation to an
      extended one, possibly and partly due to the dehydration of the methoxy group
      from water surface involved. Molecular dynamics studies of MA models derived from
      Monte Carlo calculations were also performed, which confirmed the conformational
      behavior of MAs suggested by the thermodynamic studies on the Langmuir
      monolayers.

PMID- 17524353
TI  - PEG molecular weight and lateral diffusion of PEG-ylated lipids in magnetically
      aligned bicelles.
AB  - Lateral diffusion coefficients of PEG-ylated lipids with three different
      molecular weight PEG groups (1000, 2000 and 5000) were measured in magnetically
      aligned bicelles using the stimulated echo (STE) pulsed field gradient (PEG) (1)H
      nuclear magnetic resonance (NMR) method. At concentrations below the PEG
      "mushroom-to-brush" transition, all three PEG-ylated lipids exhibited
      unrestricted lateral diffusion, with lateral diffusion coefficients comparable to
      those of corresponding non-PEG-ylated lipids and independent of PEG molecular
      weight. At concentrations above this transition, lateral diffusion slowed
      progressively with increasing concentration of PEG-ylated lipid as a result of
      surface crowding. As well, the lateral diffusion coefficients exhibited a
      pronounced decrease with increasing PEG group molecular weight and a diffusion
      time dependence indicative of obstructed diffusion. We conclude that, while
      lateral diffusion of PEG-ylated lipids within lipid bilayers is determined
      primarily by the hydrophobic anchoring group, when crowding at the lipid bilayer
      surface becomes significant, the size of the extra-membranous domain, in this
      case the PEG group, can influence lateral diffusion, leading to decreased
      diffusivity with increasing size and producing obstructed diffusion at high
      crowding. These findings imply that similar considerations will pertain to
      lateral diffusion of membrane proteins with large extra-membranous domains.

PMID- 17524354
TI  - Preattentive processing of heart cues and the perception of heart symptoms in
      congenital heart disease.
AB  - The present study was aimed at clarifying whether preattentive processing of
      heart cues results in biased perception of heart sensations in patients with
      congenital heart disease (ConHD) who are also highly trait anxious. Twenty-six
      patients with ConHD and 22 healthy participants categorized heart-related (heart
      rate) or neutral sensations (constant vibration) as either heart or neutral. Both
      sensations were evoked using a bass speaker that was attached on the chest of the
      participant. Before each physical sensation, a subliminal heart-related or
      neutral prime was presented. Biased perception of heart-sensations would become
      evident by a delayed categorization of the heart-related sensations. In line with
      the prediction, a combination of high trait anxiety and ConHD resulted in slower
      responses after a heart-related sensation that was preceded by a subliminal heart
      cue. Preattentive processing of harmless heart cues may easily elicit
      overperception of heart symptoms in highly trait anxious patients with ConHD.

PMID- 17524355
TI  - siRNA selection criteria--statistical analyses of applicability and significance.
AB  - RNA interference is a powerful tool for gene silencing, which is mediated by
      introducing siRNA. In the present study, statistical analyses of published siRNA
      selection criteria, the interpretation of some criteria and systematic searching
      for new criteria have been carried out for CGB siRNA and siRecords databases. The
      results of the analyses are as follows: (i) Our study supports the two-state
      model of the RNA-induced silencing complex (RISC). (ii) Stable 5'-S ends of a
      siRNA sequence, higher stability of the whole siRNA, and low breaking energy of
      siRNA duplex occurs in effective siRNA sequences. Also low internal stability of
      the 5'-AS terminus is preferred. (iii) Secondary structure can be successfully
      used as an RNAi selection criterion. (iv) Several published sequence criteria
      have been confirmed and also new criteria have been developed. (v) Also a Target
      Patterns criterion, which is comparable or better than the best known criteria,
      has been created.

PMID- 17524356
TI  - Sodium butyrate modifies the stabilizing complexes of tyrosine hydroxylase mRNA.
AB  - Multiple mechanisms regulate the expression of the tyrosine hydroxylase (Th)
      gene, which encodes the rate-limiting enzyme in the biosynthesis of
      catecholamines. Sodium butyrate (SOB), a physiological histone deacetylase (HDAC)
      inhibitor, was reported to stimulate the Th gene promoter activity in reporter
      gene assays. However, the expression of the endogenous Th gene in PC12 cells was
      reported to be either stimulated or inhibited by SOB. Here, we report that SOB
      and other HDAC inhibitors drastically (up to 90%) and reversibly decrease the
      level of TH mRNA in PC12 cells. We also show that SOB does not influence the
      transcription initiation rate of the Th gene but perturbs the formation of
      protein-RNA complexes at the 3'UTR of the gene. Our results suggest that SOB
      inhibits the expression of the Th gene by destabilizing TH mRNAs.

PMID- 17524357
TI  - Induction of cyclooxygenase-2 by ginsenoside Rd via activation of CCAAT-enhancer
      binding proteins and cyclic AMP response binding protein.
AB  - Panax ginseng is a widely used herbal medicine in East Asia and is reported to
      have a variety of pharmacological effects against cardiovascular diseases and
      cancers. Here we show a unique effect of ginsenoside Rd (Rd) on cyclooxygenase-2
      (COX-2) expression in RAW264.7 macrophages. Rd (100 microg/ml), but not other
      ginsenosides induced COX-2 and increased prostaglandin E(2) production. Gel shift
      and Western blot analyses using nuclear fractions revealed that Rd increased both
      the DNA binding of and the nuclear levels of CCAAT/enhancer binding protein
      (C/EBP)alpha/beta and cyclic AMP response element binding protein (CREB), but not
      of p65, in RAW264.7 cells. Moreover, Rd increased the luciferase reporter gene
      activity in cells transfected with a 574-bp mouse COX-2 promoter construct. Site
      specific mutation analyses confirmed that Rd-mediated transcriptional activation
      of COX-2 gene was regulated by C/EBP and CREB. These results provide evidence
      that Rd activated C/EBP and CREB, and that the activation of C/EBP and CREB
      appears to be essential for induction of COX-2 in RAW264.7 cells.

PMID- 17524358
TI  - 17Beta-estradiol induces ERbeta up-regulation via p38/MAPK activation in colon
      cancer cells.
AB  - Estrogen receptors (ERalpha and ERbeta) mediate opposite functions on cancer
      growth induced by 17beta-estradiol (E2). E2 binding to ERalpha induces a cancer
      promoting response, whereas E2 binding to ERbeta exerts a protective action
      against cancer growth. Moreover, E2 can diversely modulate the ERalpha and ERbeta
      levels intensifying or decreasing their actions in target tissues. Only molecular
      mechanisms at the root of E2 ability to down-regulate the ERalpha levels are
      known. Here, we report the first molecular mechanism underlying E2-induced ERbeta
      up-regulation in DLD-1 colon cancer cells. E2 induces a short term (2 and 4h
      after stimulation) translation of ERbeta mRNA followed by a late (24h after
      stimulation) enhanced transcription. Both processes required the E2-induced
      persistent and palmitoylation-dependent p38/MAPK activation. Overall, our data
      suggest a finely tuned control exerted by rapid signals on different cellular
      molecular events important for the protective effects of E2 against colon cancer
      growth.

PMID- 17524359
TI  - Exon grafting yields a "two active-site" lysozyme.
AB  - The design of enzymes with enhanced stability and activity has long been a goal
      in protein engineering. We report a strategy to engineer an additional active
      site for human lysozyme, grafted the entire human lysozyme exon 2, which encodes
      the catalytically competent domain, into the gene at a position corresponding to
      an exposed loop region in the translated protein. Exon 2 grafting created a novel
      lysozyme with twice the activity of the wild type enzyme, equal activity came
      from each of the two active sites. We dissected the contributions of each active
      site using site-directed mutagenesis of the catalytic doublets of (E35A/D53A),
      circular dichroism, fluorescence spectra, and molecular modeling. Temperature and
      pH stability of the "two active-site" enzyme were similar to those of wild-type
      lysozyme. Thus, we provide a novel strategy for engineering the active site of
      enzymes.

PMID- 17524360
TI  - BDNF induction with mild exercise in the rat hippocampus.
AB  - Although chronic voluntary physical activity has been shown to enhance
      hippocampal brain-derived neurotrophic factor (BDNF) expression in animals, the
      effects of forced exercise on a treadmill have not been fully investigated. We
      assessed induction of c-fos and BDNF expression with acute exercise at different
      running intensities. The mRNA for c-fos, a marker for neuronal activation, was up
      regulated even under low-intensity running (15 m/min), although its induction
      appeared to be intensity dependent. On the other hand, increases in BDNF mRNA and
      protein were seen only at low-intensity running. At moderate-intensity running
      (25 m/min) which elevated blood lactate and corticosterone levels, induction of
      BDNF mRNA, but not its protein, was even depressed. Our study shows the first
      evidence that with an acute low-intensity exercise that is minimally stressful,
      hippocampal activation and BDNF expression can be achieved lending support to the
      idea that mild exercise could yield to greater benefits in hippocampal functions
      compared to the more strenuous forms.

PMID- 17524361
TI  - The insulin-like growth factor 1 (IGF-1) receptor is a substrate for gamma
      secretase-mediated intramembrane proteolysis.
AB  - Several type-1 membrane proteins undergo regulated intramembrane proteolysis
      resulting in the generation of biologically active protein fragments. Presenilin
      dependant gamma-secretase activity is central to this event and includes amyloid
      precursor protein (APP), Notch and ErbB4 as substrates. Here we show that the
      insulin-like growth factor 1 receptor (IGF-IR) undergoes regulated intramembrane
      proteolysis. A metalloprotease-dependant ectodomain-shedding event generates a
      approximately 52 kDa IGF-IR-carboxyl terminal domain (CTD). The IGF-IR-CTD is
      consequentially a substrate for gamma-secretase cleavage, liberating a
      approximately 50 kDa intracellular domain (ICD) that can be inhibited by a
      specific gamma-secretase inhibitor. This study suggests that the IGF-IR is a
      substrate for gamma-secretase and may mediate a function independent of its role
      as a receptor tyrosine kinase.

PMID- 17524362
TI  - Particulate and soluble adenylyl cyclases participate in the sperm acrosome
      reaction.
AB  - cAMP is important in sea urchin sperm signaling, yet the molecular nature of the
      adenylyl cyclases (ACs) involved remained unknown. These cells were recently
      shown to contain an ortholog of the mammalian soluble adenylyl cyclase (sAC).
      Here, we show that sAC is present in the sperm head and as in mammals is
      stimulated by bicarbonate. The acrosome reaction (AR), a process essential for
      fertilization, is influenced by the bicarbonate concentration in seawater. By
      using functional assays and immunofluorescence techniques we document that sea
      urchin sperm also express orthologs of multiple isoforms of transmembrane ACs
      (tmACs). Our findings employing selective inhibitors for each class of AC
      indicate that both sAC and tmACs participate in the sperm acrosome reaction.

PMID- 17524363
TI  - Nucleolar protein Nop25 is involved in nucleolar architecture.
AB  - Nop25 is a putative RNA binding nucleolar protein associated with rRNA
      transcription. The present study was undertaken to determine the crucial function
      of Nop25 in the nucleolus. When N-terminal amino acids of Nop25 were
      overexpressed as a dominant negative effector in cells, the nucleolus was
      fragmented into small components. Knockdown of Nop25 by RNA interference also
      induced drastic nucleolar fragmentation. These results suggest that Nop25 is
      involved in nucleolar architecture and maintenance. Although nucleolar
      fragmentation induced the dispersion of nucleolar proteins from the nucleolus, it
      did not lead to cell cycle arrest or apoptosis, suggesting no effect of nucleolar
      fragmentation on the transcription and processing of rRNA molecules and
      subsequent ribosome biogenesis. Studies on Nop25 may provide new information on
      nucleolar organization related to nucleolar architecture and function.

PMID- 17524364
TI  - Apoptosis related protein 3, an ATRA-upregulated membrane protein arrests the
      cell cycle at G1/S phase by decreasing the expression of cyclin D1.
AB  - Human Apr3 was first cloned from HL-60 cells treated by ATRA. In this study, we
      further demonstrated that Apr3 could be obviously upregulated by ATRA in many
      other ATRA sensitive cells, suggesting a common role of Apr3 in ATRA effects.
      Indirect immunofluorescence assay indicates that Apr3 is a membrane protein,
      while its truncated form without the predicted transmembrane and intracellular
      domain, was likely a secreted one. Furthermore, FACS analysis showed that Apr3
      overexpression could cause an obvious G1/S phase arrest which might be induced by
      dramatic reduction of cyclin D1 expression. Strikingly, the truncated Apr3
      antagonized the negative role of Apr3 on cell cycle and cyclin D1. Taken
      together, our data suggest that Apr3 should play an important role in ATRA signal
      pathway and the predicted transmembrane and/or the intracellular domain mediates
      Apr3 membrane localization and is vital for the negative regulation on cell cycle
      and cyclin D1.

PMID- 17524365
TI  - Effects of fluid flow on voltage-dependent calcium channels in rat vascular
      myocytes: fluid flow as a shear stress and a source of artifacts during patch
      clamp studies.
AB  - We examined the effects of fluid flow on L-type voltage-dependent Ca(2+) channel
      (VDCC(L)) currents in rat vascular myocytes using the nystatin perforated patch
      clamp technique. The effect of fluid flow on the liquid (bathing solution)-metal
      (Ag/AgCl ground electrode) junction potential was also studied. With a fluid flow
      of 0-10 ml/min, changes in the junction potential of up to 5 mV were observed in
      proportion to the flow rate. Accordingly, fluid flow shifted the current-voltage
      (I-V) relationship of the recorded VDCC(L) currents in a positive direction. In
      addition to these shifts, fluid flow also increased the peak VDCC(L) current,
      suggesting some modulatory role for fluid flow in VDCC(L) currents. The use of a
      3-M KCl agar-bridge between the ground electrode and bathing solution abnegated
      the potential shifts, and fluid flow increased the VDCC(L) currents in a voltage
      independent manner. These results suggest that the bathing fluid flow can be both
      a source of erroneous voltage shift between liquid and metal junctions in the
      patch-clamp configuration and an important shear stress for the cells. The
      facilitation of VDCC(L) currents by fluid flow in vascular myocytes may
      contribute to the myogenic contraction of blood vessels. The mechanism by which
      fluid flow causes the voltage shift is vigorously discussed.

PMID- 17524366
TI  - Trafficking motifs in the SARS-coronavirus nucleocapsid protein.
AB  - The severe acute respiratory syndrome-coronavirus nucleocapsid (N) protein is
      involved in virus replication and modulation of cell processes. In this latter
      respect control may in part be achieved through the sub-cellular localisation of
      the protein. N protein predominately localises in the cytoplasm (the site of
      virus replication and assembly) but also in the nucleus/nucleolus. Using a
      combination of live-cell and confocal microscopy coupled to mutagenesis we
      identified a cryptic nucleolar localisation signal in the central part of the N
      protein. In addition, based on structural comparison to the avian coronavirus N
      protein, a nuclear export signal was identified in the C-terminal region of the
      protein.

PMID- 17524367
TI  - The distribution of the DEK protein in mammalian chromatin.
AB  - DEK is an abundant and ubiquitous chromatin protein. Here we investigate whether
      DEK is regularly distributed in the chromatin of human HeLa cells. We show that
      DEK appears to be excluded from the heterochromatic compartment. However, DEK
      seems to colocalize with a subfraction of chromatin bearing acetylated histone
      H4. We examined certain DNA sequences in specifically immunoprecipitated
      chromatin for four selected human genes. We found that most of the investigated
      gene sequences were moderately enriched in immunoprecipitated chromatin. In
      contrast, a promoter-proximal element of the human TOP1 gene was highly enriched
      in the chromatin immunoprecipitates. This enrichment was lost when cells were
      treated with alpha-amanitin showing that DEK binds to this particular site only
      when the TOP1 gene is actively expressed. Our conclusion is that DEK could serve
      as an architectural protein at the promoter or enhancer sites of a subfraction of
      human genes.

PMID- 17524368
TI  - Modulation of hepatic microsomal triglyceride transfer protein (MTP) induced by S
      nitroso-N-acetylcysteine in ob/ob mice.
AB  - We evaluated the effects of a potent NO donor, S-nitroso-N-acetylcysteine (SNAC),
      on microsomal triglyceride transfer protein (MTP) expression in ob/ob mice. NAFLD
      was induced in male ob/ob mice using a methionine-choline deficient diet (MCD)
      concomitantly with oral SNAC fed solution (n=5) or vehicle (control; n=5) by
      gavage daily for 4 weeks. Livers were collected for histology and for assessing
      MTP by RT-qPCR, Western blot, immunohistochemistry and immunogold electron
      microscopy analyses. Histological analysis showed diffuse macro and
      microvesicular steatosis, moderate hepatocellular ballooning and moderate
      inflammatory infiltrate in ob/ob mice fed the MCD diet. With SNAC, mice showed a
      marked reduction in liver steatosis (p<0.01), in parenchymal inflammation
      (p=0.02) and in MTP protein immunoexpression in zone III (p=0.05). Moreover, SNAC
      caused reduction of MTP protein in Western blot analysis (p<0.05). In contrast,
      MTP mRNA content was significantly higher (p<0.05) in mice receiving SNAC. Immuno
      electron microscopy showed MTP localized in the rough endoplasmic reticulum of
      hepatocytes in both treated and untreated groups. However with SNAC treatment,
      MTP was also observed surrounding fat globules. Histological improvement mediated
      by a nitric oxide donor is associated with significantly altered expression and
      distribution of MTP in this animal model of fatty liver disease. Further studies
      are in progress to examine possible mechanisms and to develop SNAC as a possible
      therapy for human fatty liver disease.

PMID- 17524369
TI  - Acute selective serotonin reuptake inhibitors increase conditioned fear
      expression: blockade with a 5-HT(2C) receptor antagonist.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) effectively treat
      various anxiety disorders, although symptoms of anxiety are often exacerbated
      during early stages of treatment. We previously reported that acute treatment
      with the SSRI citalopram enhances the acquisition of auditory fear conditioning,
      which is consistent with the initial anxiogenic effects reported clinically.
      Here, we extend our findings by assessing the effects of acute SSRI treatment on
      the expression of previously acquired conditioned fear. METHODS: Rats underwent
      fear conditioning drug-free. Tone-evoked fear responses were tested after drug
      treatment the following day. This protocol more closely resembles the clinical
      setting than pre-conditioning treatment, because it evaluates effects of
      treatment on a pre-existing fear rather than on the formation of a new fear
      memory. RESULTS: A single pre-testing injection of the SSRIs citalopram or
      fluoxetine significantly increased fear expression. There was no effect of the
      antidepressant tianeptine or the norepinephrine reuptake inhibitor tomoxetine,
      indicating that this effect is specific to SSRIs. The SSRI-induced enhancement in
      fear expression was not blocked by tropisetron, a 5-HT(3) receptor antagonist,
      but was blocked by SB 242084, a specific 5-HT(2C) receptor antagonist.
      CONCLUSIONS: Enhanced activation of 5-HT(2C) receptors might be a mechanism for
      the anxiogenic effects of SSRIs observed initially during treatment.

PMID- 17524370
TI  - Regulation of neuronal PLCgamma by chronic morphine.
AB  - Alterations in neurotrophic signaling pathways may contribute to the changes in
      the mesolimbic dopamine system induced by chronic morphine exposure. In a rat
      model of morphine dependence, we previously identified increased levels of
      phospholipase C gamma-1 (PLCgamma1) immunoreactivity specifically within the
      ventral tegmental area (VTA) following chronic morphine treatment. Using an
      antibody specific for the tyrosine-phosphorylated, activated form of PLCgamma1,
      we now show that chronic morphine also significantly upregulates PLCgamma1
      activity in the VTA, as well as in the nucleus accumbens and hippocampus, regions
      which are also implicated in the reinforcing properties of morphine. In contrast,
      no increase in PLCgamma1 activity was found in the substantia nigra or dorsal
      striatum. HSV-mediated overexpression of PLCgamma1 in PC12 cells induced ERK
      activation via a mechanism dependent, in part, on both MAP-ERK kinase (MEK) and
      protein kinase C. PLCgamma1 overexpression in the VTA similarly induced ERK
      activation in the VTA in vivo. As chronic morphine treatment has been shown to
      increase ERK activity within the VTA, the current results suggest that increased
      PLCgamma1 activity may be an upstream mediator of this effect.

PMID- 17524371
TI  - Brain stimulation reward is integrated by a network of electrically coupled GABA
      neurons.
AB  - The neural substrate of brain stimulation reward (BSR) has eluded identification
      since its discovery more than a half-century ago. Notwithstanding the
      difficulties in identifying the neuronal integrator of BSR, the mesocorticolimbic
      dopamine (DA) system originating in the ventral tegmental area (VTA) of the
      midbrain has been implicated. We have previously demonstrated that the firing
      rate of a subpopulation of gamma-aminobutyric acid (GABA) neurons in the VTA
      increases in anticipation of BSR. We show here that GABA neurons in the VTA,
      midbrain, hypothalamus, and thalamus of rats express connexin-36 (Cx36) gap
      junctions (GJs) and couple electrically upon DA application or by stimulation of
      the internal capsule (IC), which also supports self-stimulation. The threshold
      for responding for IC self-stimulation was the threshold for electrical coupling
      between GABA neurons, the degree of responding for IC self-stimulation was
      proportional to the magnitude of electrical coupling between GABA neurons, and GJ
      blockers increased the threshold for IC self-stimulation without affecting
      performance. Thus, a network of electrically coupled GABA neurons in the ventral
      brain may form the elusive neural integrator of BSR.

PMID- 17524372
TI  - Methamphetamine exposure antagonizes N-methyl-D-aspartate receptor-mediated
      neurotoxicity in organotypic hippocampal slice cultures.
AB  - Glutamatergic systems have been increasingly recognized as mediators of
      methamphetamine's (METH) pharmacological effects though little is known about the
      means by which METH interacts with glutamate receptors. The present studies
      examined effects of METH (0.1-100 microM) on [3H]MK-801 binding to membranes
      prepared from adult rat cortex, hippocampus and cerebellum, as well as the
      neurotoxicity produced by 24-h exposure to N-methyl-D-aspartate (5-10 microM;
      NMDA) employing organotypic hippocampal slice cultures of neonatal rat. Co
      incubation of [3H]MK-801 with METH (0.1-100 microM) did not reduce
      dextromethorphan (1 mM)-displaceable ligand binding. Exposure of slice cultures
      to NMDA for 24-h produced increases in uptake of the non-vital fluorescent marker
      propidium iodide (PI) of 150-500% above control levels, most notably, in the CA1
      region pyramidal cell layer. Co-exposure to METH (>1.0 microM) with NMDA (5
      microM) reduced PI uptake by approximately 50% in each subregion, though the CA1
      pyramidal cell layer was markedly more sensitive to the protective effects of
      METH exposure. In contrast, METH exposure did not reduce PI uptake stimulated by
      24-h exposure to 10 microM NMDA. Co-exposure to the NMDA receptor antagonist D-2
      amino-5-phosphonovaleric acid (20 microM) prevented toxicity produced by exposure
      to 5 or 10 microM NMDA. These findings indicate that the pharmacological effects
      of short-term METH exposure involve inhibition of NMDA receptor-mediated neuronal
      signaling, not reflective of direct channel inhibition at an MK-801-sensitive
      site.

PMID- 17524373
TI  - Cobalamin deficiency-induced down-regulation of p75-immunoreactive cell levels in
      rat central nervous system.
AB  - We investigated immunoreactivity for p75 neurotrophin receptor (NTR) in the
      spinal cord white matter and septum of rats made cobalamin-deficient (Cbl-D) by
      means of total gastrectomy or a Cbl-D diet. Cbl deficiency down-regulates p75NTR
      immunoreactive cell levels in spinal cord white matter and septum with different
      time courses. On the whole, the spinal cord white matter seems to be more
      affected in terms of p75NTR-immunoreactive cells, most of which are astrocytes.
      The p75NTR-immunoreactive cell levels in the spinal cord white matter and septum
      normalized in rats treated with Cbl (scheme b) and killed 4 months after total
      gastrectomy. However, Western blot analysis of p75NTR in the spinal cords of Cbl
      D rats shows increased p75NTR protein levels, which are resistant to Cbl
      replacement. These findings demonstrate that a neurotrophic vitamin (Cbl)
      positively regulates the levels of a neurotrophic receptor (p75NTR) (at least in
      terms of immunohistochemistry) in rat central nervous system, although the
      underlying mechanism(s) are still unknown.

PMID- 17524374
TI  - Practical synthesis of (-)-1-amino-1-deoxy-myo-inositol from achiral precursors.
AB  - A new synthesis of enantiomerically pure 1-amino-1-deoxy-myo-inositol is
      reported. The route described employs p-benzoquinone, an achiral compound, as the
      starting material to give conduritol B tetraacetate in three steps. Kinetic
      resolution of this compound using a palladium catalyst with a chiral ligand
      allows access to a conduritol B tetraester in high enantiomeric excess. This
      compound is transformed into tetrabenzyl conduritol B epoxide, which is
      regioselectively opened with azide to give the key azidocyclitol. Final
      transformation into (-)-1-amino-1-deoxy-myo-inositol hydrochloride is achieved in
      four synthetic steps. This sequence allows the synthesis of this compound in high
      enantiomeric purity in a semi-preparative scale.

PMID- 17524375
TI  - Modification of HDL3 by mild oxidative stress increases ATP-binding cassette
      transporter 1-mediated cholesterol efflux.
AB  - OBJECTIVE: Elevated levels of high-density lipoprotein (HDL) cholesterol are
      inversely related to the risk of cardiovascular disease. The anti-atherosclerotic
      function of HDL is mainly ascribed to its role in reverse cholesterol transport,
      and requires the integrity of HDL structure. Experimental evidence suggests that
      the ability of HDL to promote removal of excess cholesterol from peripheral cells
      is impaired upon oxidation. On the other hand, tyrosylation of HDL enhances its
      protective function, suggesting that not all forms of modified lipoprotein may be
      atherogenic. In the present study we investigated the effect of a mild oxidation
      of HDL(3) on its function as cholesterol acceptor. METHODS AND RESULTS: A mild
      oxidative stress (induced by 15 min exposure of HDL(3) to 1 microM Cu(++) or to
      15-lipoxygenase) caused the formation of pre-beta-migrating particles. Compared
      to native lipoprotein, mildly modified HDL(3) induced a significant ATP-binding
      cassette transporter 1 (ABCA1)-mediated increase of cholesterol and phospholipids
      efflux from J774 macrophages. This effect was abolished by an inhibitor of ABCA1
      mediated lipid efflux (glyburide) and was absent in Tangier fibroblasts.
      CONCLUSIONS: A mild oxidative modification of HDL(3) may improve its function as
      cholesterol acceptor, increasing ABCA1-mediated lipid efflux from macrophages, a
      process that may reduce foam cell formation.

PMID- 17524376
TI  - Balancing reactivity against selectivity: the evolution of protein S
      nitrosylation as an effector of cell signaling by nitric oxide.
AB  - Produced by the action of lightning in the atmosphere of the pre-biotic earth,
      nitric oxide (NO) is a free radical molecule that provided the major nitrogen
      source for development of life. Remarkably, when atmospheric sources of NO became
      restrictive, organisms evolved the capacity for NO biosynthesis and NO took on
      bioregulatory roles. We now recognize NO as an ancestral regulator of diverse and
      important biological functions, acting throughout the phylogenetic tree. In
      mammals, NO has been implicated as a pivotal regulator of virtually every major
      physiological system. The bioactivities of NO, and reactive species derived from
      NO, arise predominantly from their covalent addition to proteins. Importantly, S
      nitrosylation of protein cysteine (Cys) residues has emerged as a preeminent
      effector of NO bioactivity. How and why NO selectively adds to particular Cys
      residues in proteins is poorly understood, yet fundamental to how NO communicates
      its bioactivities. Also, evolutionary pressures that have shaped S-nitrosylation
      as a biosignaling modality are obscure. Considering recently recognized NO
      signaling paradigms, we speculate on the origin of NO signaling in biological
      systems and the molecular adaptations that have endowed NO with the ability to
      selectively target a subset of protein Cys residues that mediate biosignaling.

PMID- 17524377
TI  - Sarcoplasmic reticulum Ca2+ release channel complex and automatism: a matter of
      fine tuning.

PMID- 17524379
TI  - Thermodynamic study on competitive solubilization of cholesterol and beta
      sitosterol in bile salt micelles.
AB  - Differences in the preferential solubilization of cholesterol and competitive
      solubilizates (beta-sitosterol and aromatic compounds) in bile salt micelles was
      systematically studied by changing the molar ratio of cholesterol to competitive
      solubilizates. The cholesterol solubility in a mixed binary system (cholesterol
      and beta-sitosterol) was almost half that of the cholesterol alone system,
      regardless of the excess beta-sitosterol quantity added. On the other hand, the
      mutual solubilities of cholesterol and pyrene were not inhibited by their
      presence in binary mixed crystals. Finally, the cholesterol solubility was
      measured by changing the alkyl chain length of n-alkylbenzenes. When
      tetradecylbenzene was added to the bile solution, the cholesterol solubility
      decreased slightly and was below the original cholesterol solubility. Based on
      Gibbs energy change (DeltaG degrees ) for solubilization, chemicals that inhibit
      cholesterol solubility in their combined crystal systems showed a larger negative
      DeltaG degrees value than cholesterol alone.

PMID- 17524378
TI  - Maternal microchimerism leads to the presence of interleukin-2 in interleukin-2
      knock out mice: implications for the role of interleukin-2 in thymic function.
AB  - The role of interleukin-2 (IL-2) in thymic development is uncertain. Not
      surprisingly, IL-2 knockout (KO) mice have been used to address this question.
      However, as we report here, such mice are chimeric, containing both IL-2 KO cells
      and IL-2-expressing cells transferred in utero from their heterozygous mothers.
      These cells produce IL-2 in amounts detectable by conventional means, and their
      presence in lymphoid tissues confounds efforts to define the true IL-2 KO
      phenotype. To minimize the amount of IL-2 available to the thymus, we subjected
      recombinase activating gene-1 KO mice to bone marrow transplantation using IL-2
      KO donors, and then followed the reconstitution of the thymus. The thymuses of
      these mice became increasingly aberrant over time, including abnormalities in
      both stromal cells and thymocytes. These results demonstrate that IL-2 is
      critical to several aspects of thymic function, a finding previously obscured by
      the presence of IL-2 in IL-2 KO mice.

PMID- 17524380
TI  - Changes in the components of biliary and plasma lipids in selenium-deficient
      rats.
AB  - We constructed a chronic oxidative stress model in which Se-deficient diet was
      fed to male Wister rats for 8 weeks. As expected, effects of oxidative damage,
      including Fe accumulation and increase in peroxidized lipids, were identified in
      the liver owing to the lack of glutathione peroxidase. Although the oxidative
      stress caused Fe accumulation in the liver, the Fe concentration in bile of the
      SeD rat was almost the same as that in the control rats. The constant excretion
      of Fe into bile supported the Fe accumulation in the liver. No differences were
      observed in the principal components of biliary lipids, i.e., bile acids,
      phospholipids, and cholesterol, between the two groups; moreover, these trends
      were also reflected in the plasma. Due to the trapping of reactive oxygen
      species, only bilirubin concentrations in the bile and plasma were decreased in
      the SeD group, when compared with those in the control group. Measurement of
      bilirubin concentration may be used as a supplemental oxidative stress marker.

PMID- 17524381
TI  - The thermotropic phase behaviour and phase structure of a homologous series of
      racemic beta-D-galactosyl dialkylglycerols studied by differential scanning
      calorimetry and X-ray diffraction.
AB  - The thermotropic phase behaviour of aqueous dispersions of some synthetic 1,2-di
      O-alkyl-3-O-(beta-D-galactosyl)-rac-glycerols (rac-beta-D-GalDAGs) with both odd
      and even hydrocarbon chain lengths was studied by differential scanning
      calorimetry (DSC), small-angle (SAXS) and wide-angle (WAXS) X-ray diffraction.
      DSC heating curves show a complex pattern of lamellar (L) and nonlamellar (NL)
      phase polymorphism dependent on the sample's thermal history. On cooling from 95
      degrees C and immediate reheating, rac-beta-D-GalDAGs typically show a single,
      strongly energetic phase transition, corresponding to either a lamellar
      gel/liquid-crystalline (L(beta)/L(alpha)) phase transition (N< or =15 carbon
      atoms) or a lamellar gel/inverted hexagonal (L(beta)/H(II)) phase transition (N>
      or =16). At higher temperatures, some shorter chain compounds (N=10-13) exhibit
      additional endothermic phase transitions, identified as L/NL phase transitions
      using SAXS/WAXS. The NL morphology and the number of associated intermediate
      transitions vary with hydrocarbon chain length. Typically, at temperatures just
      above the L(alpha) phase boundary, a region of phase coexistence consisting of
      two inverted cubic (Q(II)) phases are observed. The space group of the cubic
      phase seen on initial heating has not been determined; however, on further
      heating, this Q(II) phase disappears, enabling the identification of the second
      Q(II) phase as Pn3 m (space group Q(224)). Only the Pn3 m phase is seen on
      cooling. Under suitable annealing conditions, rac-beta-D-GalDAGs rapidly form
      highly ordered lamellar-crystalline (L(c)) phases at temperatures above (N< or
      =15) or below (N=16-18) the L(beta)/L(alpha) phase transition temperature (T(m)).
      In the N< or =15 chain length lipids, DSC heating curves show two overlapping,
      highly energetic, endothermic peaks on heating above T(m); corresponding changes
      in the first-order spacings are observed by SAXS, accompanied by two different,
      complex patterns of reflections in the WAXS region. The WAXS data show that there
      is a difference in hydrocarbon chain packing, but no difference in bilayer
      dimensions or hydrocarbon chain tilt for these two L(c) phases (termed L(c1) and
      L(c2), respectively). Continued heating of suitably annealed, shorter chain rac
      beta-D-GalDAGs from the L(c2) phase results in a phase transition to an L(alpha)
      phase and, on further heating, to the same Q(II) or H(II) phases observed on
      first heating. On reheating annealed samples with longer chain lengths, a subgel
      phase is formed. This is characterized by a single, poorly energetic endotherm
      visible below the T(m). SAXS/WAXS identifies this event as an L(c)/L(beta) phase
      transition. However, the WAXS reflections in the di-16:0 lipid do not entirely
      correspond to the reflections seen for either the L(c1) or L(c2) phases present
      in the shorter chain rac-beta-D-GalDAGs; rather these consist of a combination of
      L(c1), L(c2) and L(beta) reflections, consistent with DSC data where all three
      phase transitions occur within a span of 5 degrees C. At very long chain lengths
      (N> or =19), the L(beta)/L(c) conversion process is so slow that no L(c) phases
      are formed over the time scale of our experiments. The L(beta)/L(c) phase
      conversion process is significantly faster than that seen in the corresponding
      rac-beta-D-GlcDAGs, but is slower than in the 1,2-sn-beta-D-GalDAGs already
      studied. The L(alpha)/NL phase transition temperatures are also higher in the rac
      beta-D-GalDAGs than in the corresponding rac-beta-D-GlcDAGs, suggesting that the
      orientation of the hydroxyl at position 4 and the chirality of the glycerol
      molecule in the lipid/water interface influence both the L(c) and NL phase
      properties of these lipids, probably by controlling the relative positions of
      hydrogen bond donors and acceptors in the polar region of the membrane.

PMID- 17524382
TI  - Performance characteristics of the IMMULITE 2000 androstenedione assay.

PMID- 17524383
TI  - Analytical interferences of drugs in the chemical examination of urinary protein.
AB  - OBJECTIVES: To evaluate the potential analytical interference of 24 drugs in the
      urinary protein. DESIGN AND METHODS: The analysis was done using Multistix 10SG
      and comparing the results of controls with urine samples supplemented with drugs.
      RESULTS: Positive interferences occurred with ciprofloxacin, quinine and
      chloroquine in supratherapeutical concentrations, while chloroquine interfered
      also in therapeutical concentration. CONCLUSIONS: False proteinuria in test
      strips can lead to erroneous interpretations with repercussion in clinical
      procedures and higher costs to the health system.

PMID- 17524384
TI  - Diagnosis of X-linked adrenoleukodystrophy in blood leukocytes.
AB  - OBJECTIVES: Our aim was to replace cultured skin fibroblasts in the diagnosis of
      X-linked adrenoleukodystrophy (X-ALD) by peripheral blood cells. DESIGN AND
      METHODS: Very long chain fatty acids (VLCFAs) were analyzed in leukocytes from X
      ALD patients, heterozygotes, and controls using gas chromatography-mass
      spectrometry (GC-MS). Immunofluorescence for adrenoleukodystrophy protein (ALDP)
      was performed in mononuclear blood cell preparations of X-ALD patients known to
      be ALDP negative in fibroblasts, heterozygote relatives of these patients, and
      controls. RESULTS: All X-ALD patients were distinguishable from controls by VLCFA
      analysis in leukocytes. 91.7% of heterozygotes were identified by combined VLCFA
      analysis in leukocytes and plasma. All patients investigated lacked ALDP
      immunoreactivity in mononuclear cells, while heterozygotes showed mosaic patterns
      of positive and negative cells. CONCLUSION: Determination of VLCFAs by GC-MS in
      combination with ALDP immunofluorescence in peripheral blood cells provides a
      fast and minimally invasive diagnostic method for X-ALD, which, in contrast to
      plasma analysis, is independent of alimentary influences. Notably, joint
      evaluation of leukocytes and plasma considerably improves the identification of
      heterozygotes.

PMID- 17524385
TI  - Association of periodontitis with GSTM1/GSTT1-null variants--a pilot study.
AB  - OBJECTIVES: To analyze a possible association between glutathione-S-transferase
      T1 (GSTM1) and/or glutathione-S-transferase M1 (GSTM1) polymorphisms and chronic
      or aggressive forms of periodontitis in a Caucasian ethnic group. DESIGN AND
      METHODS: Sixty-nine chronic, 14 aggressive periodontitis and 61 controls, deeply
      analyzed from a clinical point of view, were studied for their GSTM1 and GSTT1
      polymorphisms by allelic specific PCR techniques. As a second control group, 64
      blood donors were also included. RESULTS: A significant association was found
      between GSTM1-null genotype and both chronic and aggressive periodontitis. The
      aggressive forms were associated with the double null GSTM1 and GSTT1
      combination. These results were independent of the patients' age, gender,
      hygienic habits and smoke (evaluated as tobacco smoking yes/no, cigarettes/day
      and pack years) as confirmed by multivariate logistic regression analysis.
      CONCLUSIONS: The GSTM1-null variant is statistically associated with the two
      forms of periodontitis, while the aggressive one also presents a second null
      variant: GSTT1.

PMID- 17524386
TI  - Description of a novel missense mutation of glucose-6-phosphate dehydrogenase
      gene associated with asymptomatic high enzyme deficiency.
AB  - We report a case of an asymptomatic young subject affected by severe deficiency
      of Glucose 6-phosphate dehydrogenase (G6PD) activity. A novel genetic mutation
      (G130A) in the third exon was found. We named this novel mutation the "G6PD
      RIGNANO variant". These findings may contribute to a better knowledge of
      molecular epidemiology of the G6PD mutation and may represent an additional
      variant to be studied for a deep comprehension of in vivo compensation mechanisms
      of G6PD deficiency.

PMID- 17524387
TI  - Contextual override of pragmatic anomalies: evidence from eye movements.
AB  - Readers typically experience processing difficulty when they encounter a word
      that is anomalous within the local context, such as 'The mouse picked up the
      dynamite...'. The research reported here demonstrates that by placing a sentence
      in a fictional scenario that is already well known to the reader (e.g., a Tom and
      Jerry cartoon, as a context for the example sentence above), the difficulty
      usually associated with these pragmatic anomalies can be immediately eliminated,
      as reflected in participants' eye movement behaviour. This finding suggests that
      readers can rapidly integrate information from their common ground, specifically,
      their cultural knowledge, whilst interpreting incoming text, and provides further
      evidence that incoming words are immediately integrated within the global
      discourse.

PMID- 17524388
TI  - An own-race advantage for components as well as configurations in face
      recognition.
AB  - The own-race advantage in face recognition has been hypothesized as being due to
      a superiority in the processing of configural information for own-race faces.
      Here we examined the contributions of both configural and component processing to
      the own-race advantage. We recruited 48 Caucasian participants in Australia and
      48 Chinese participants in Hong Kong, and had them study Caucasian and Chinese
      faces. After study, they were shown old faces (along with distractors) that were
      either blurred (isolating configural processing), in which high spatial
      frequencies were removed from the intact faces, or scrambled (isolating component
      processing), in which the locations of all face components were rearranged.
      Participants performed better on the memory test for own-race faces in both the
      blurred (configural) and scrambled (component) conditions, showing an own-race
      advantage for both configural and component processing. These results suggest
      that the own-race advantage in face recognition is due to a general facilitation
      in different forms of face processing.

PMID- 17524389
TI  - Effects of pharmacological inhibition of small GTPases on axon extension and
      migration of enteric neural crest-derived cells.
AB  - In the developing enteric nervous system, there is a close association between
      migrating neural crest-derived cells and the axons of early differentiating
      neurons. We used pharmacological inhibitors of small GTPases to determine if
      crest cell migration and axon growth could be uncoupled in cultured intact
      explants of embryonic mouse gut and slices of embryonic gut grown on collagen
      gels containing GDNF. Inhibition of the Rho effectors, ROCKI/II, or Rac/Cdc42
      inhibited both cell migration and neurite growth in intact explants of embryonic
      gut. The effects of both ROCKI/II and Rac/Cdc42 inhibitors were more severe on
      cell migration and axon extension in gut explants from Ret(+/-) mice than in
      explants from wildtype mice, indicating that Rho GTPases probably act downstream
      of the receptor tyrosine kinase, Ret. Inhibition of ROCKI/II had different
      effects on migration and axon extension in gut slices grown on collagen gels
      containing GDNF from that seen in intact explants of gut. We conclude that
      ROCKI/II and Rac/Cdc42 are required for both neural crest-derived cell migration
      and axon growth in the developing gut.

PMID- 17524390
TI  - Direct interaction between Teashirt and Sex combs reduced proteins, via Tsh's
      acidic domain, is essential for specifying the identity of the prothorax in
      Drosophila.
AB  - teashirt (tsh) encodes a zinc-finger protein that is thought to be part of a
      network that contributes to regionalization of the Drosophila embryo and
      establishes the domains of Hox protein function. tsh and the Hox gene Sex combs
      reduced (Scr) are essential to establish the identity of the first thoracic
      segment. We used the development of the first thoracic segment as a paradigm for
      Scr dependent regional morphological distinctions. In this specific context, we
      asked whether Tsh protein could have a direct influence on Scr activity. Here we
      present evidence that Tsh interacts directly with Scr and this interaction
      depends in part on the presence of a short domain located in the N-terminal half
      of Teashirt called "acidic domain". In vivo, expression of full length Tsh can
      rescue the tsh null phenotype throughout the trunk whereas Tsh lacking the Scr
      interacting domain rescues all the trunk defects except in the prothorax. We
      suggest this provides insights into the mechanism by which Tsh, in concert with
      Scr, specifies the prothoracic identity.

PMID- 17524391
TI  - The transcription factor Zfp423/OAZ is required for cerebellar development and
      CNS midline patterning.
AB  - The dorsal midline structure is critical for patterning the developing central
      nervous system (CNS). We show here that Zfp423/OAZ, a multiple zinc-finger
      transcription factor involved in both OE/EBF and BMP-signaling pathways, is
      required for the proper formation of forebrain and hindbrain midline structures.
      During embryogenesis, OAZ is highly expressed at the dorsal neuroepithelium
      flanking the roof plate. OAZ-deficient mice are ataxic, attributed to the
      reduction of the cerebellar vermis and some regions of the hemispheres.
      Characterization of postnatal cerebellar development shows defects in Purkinje
      cell differentiation and granule cell proliferation. In the forebrain, dorsal
      telencephalic commissural neurons project axons, but these axons fail to cross
      the midline and midline glial cells are abnormally distributed. Moreover, there
      are malformations in midline structures including the septum, thalamus and
      hypothalamus, suggesting a pivotal role of OAZ in CNS midline patterning.

PMID- 17524392
TI  - Extracellular ATP-dependent upregulation of the transcription cofactor LMO4
      promotes neuron survival from hypoxia.
AB  - Extracellular ATP is elevated by transient ischemia and is a potent signaling
      molecule in the central nervous system. ATP promotes neuron survival from serum
      starvation by activating P2Y purinergic receptors. ATP also activates IL-6
      production and phosphorylation of Stat3 that promotes neuron survival. The
      transcription cofactor LMO4 is a positive mediator of IL-6/Stat3 signaling. Here,
      we found that LMO4 and the pro-survival factor cIAP2 (cellular inhibitor of
      apoptosis protein 2) are rapidly upregulated in neurons exposed to elevated
      extracellular ATP. Blocking LMO4 upregulation using siRNA in F11 cells blunted
      cIAP2 upregulation and abolished the early protective effect of ATP. Similar
      results were obtained using primary cortical neurons from LMO4 null mice,
      suggesting that LMO4 is required for ATP to protect neurons from hypoxia-induced
      apoptosis. Whereas increased Stat3 phosphorylation occurs after LMO4 and cIAP2
      induction, the rapid upregulated phosphorylation of ERK and CREB may account for
      increased LMO4 and cIAP2 by ATP. ATP signaling through ERK and CREB activated
      LMO4 promoters and ERK activation increased LMO4 protein stability in F11 cells.
      Taken together, our studies reveal that LMO4 is a rapidly induced downstream
      effector of ATP signaling that promotes neuron survival from hypoxia.

PMID- 17524394
TI  - Intermediate filaments and stress.
AB  - Before we can explain why so many closely related intermediate filament genes
      have evolved in vertebrates, while maintaining such dramatically tissue specific
      expression, we need to understand their function. The best evidence for
      intermediate filament function comes from observing the consequences of mutation
      and mis-expression, primarily in human tissues. Mostly these observations suggest
      that intermediate filaments are important in allowing individual cells, the
      tissues and whole organs to cope with various types of stress, in health and
      disease. Exactly how they do this is unclear and many aspects of cell dysfunction
      have been associated with intermediate filaments to date. In particular, it is
      still not clear whether the non-mechanical functions now being attributed to
      intermediate filaments are primary functions of these structural proteins, or
      secondary consequences of their function to respond to mechanical stress. We
      discuss selected situations in which responses to stress are clearly influenced
      by intermediate filaments.

PMID- 17524393
TI  - Cell shape regulates global histone acetylation in human mammary epithelial
      cells.
AB  - Extracellular matrix (ECM) regulates cell morphology and gene expression in vivo;
      these relationships are maintained in three-dimensional (3D) cultures of mammary
      epithelial cells. In the presence of laminin-rich ECM (lrECM), mammary epithelial
      cells round up and undergo global histone deacetylation, a process critical for
      their functional differentiation. However, it remains unclear whether lrECM
      dependent cell rounding and global histone deacetylation are indeed part of a
      common physical-biochemical pathway. Using 3D cultures as well as nonadhesive and
      micropatterned substrata, here we showed that the cell 'rounding' caused by lrECM
      was sufficient to induce deacetylation of histones H3 and H4 in the absence of
      biochemical cues. Microarray and confocal analysis demonstrated that this
      deacetylation in 3D culture is associated with a global increase in chromatin
      condensation and a reduction in gene expression. Whereas cells cultured on
      plastic substrata formed prominent stress fibers, cells grown in 3D lrECM or on
      micropatterns lacked these structures. Disruption of the actin cytoskeleton with
      cytochalasin D phenocopied the lrECM-induced cell rounding and histone
      deacetylation. These results reveal a novel link between ECM-controlled cell
      shape and chromatin structure and suggest that this link is mediated by changes
      in the actin cytoskeleton.

PMID- 17524396
TI  - Branched chain alpha-keto acid dehydrogenase, E1-beta subunit gene is associated
      with premature ovarian failure.
AB  - Genetic variants of the human branched chain alpha-keto acid dehydrogenase, E1
      beta subunit (BCKDHB) gene were identified and they have been associated with
      premature ovarian failure (POF). Reconstructed haplotype from these variants was
      also associated with POF.

PMID- 17524395
TI  - Softness, strength and self-repair in intermediate filament networks.
AB  - One cellular function of intermediate filaments is to provide cells with
      compliance to small deformations while strengthening them when large stresses are
      applied. How IFs accomplish this mechanical role is revealed by recent studies of
      the elastic properties of single IF protein polymers and by viscoelastic
      characterization of the networks they form. IFs are unique among cytoskeletal
      filaments in withstanding large deformations. Single filaments can stretch to
      more than 3 times their initial length before breaking, and gels of IF withstand
      strains greater than 100% without damage. Even after mechanical disruption of
      gels formed by crossbridged neurofilaments, the elastic modulus of these gels
      rapidly recovers under conditions where gels formed by actin filaments are
      irreversibly ruptured. The polyelectrolyte properties of IFs may enable
      crossbridging by multivalent counterions, but identifying the mechanisms by which
      IFs link into bundles and networks in vivo remains a challenge.

PMID- 17524397
TI  - Incubator management in an assisted reproductive technology laboratory.
AB  - OBJECTIVE: To study the effect of incubator management on assisted reproductive
      technology (ART) outcomes. DESIGN: Series of retrospective and controlled,
      randomized studies. SETTING: Tertiary care infertility practice. PATIENT(S):
      Mammalian gametes/embryos. INTERVENTION(S): Evaluation of human and bovine
      oocytes/embryos cultured in various environmental conditions. MAIN OUTCOME
      MEASURE(S): Fertilization and embryo development rate as well as clinical
      pregnancy rate (PR). CONCLUSION(S): Here we review the general topic of incubator
      management as it pertains to ART. Discussed within the context of this article
      will be our experiences as they relate to incubator management. Details as they
      apply to incubator environment also will include gamete/embryo positions within
      incubator, air quality, and quality control.

PMID- 17524398
TI  - Exposure to human chorionic gonadotropin during in vitro maturation does not
      improve the maturation rate and developmental potential of immature oocytes from
      patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the effects of human chorionic gonadotropin (hCG) in
      culture medium on the in vitro maturation (IVM) and subsequent developmental
      potential of human immature oocytes. DESIGN: Prospective, randomized study.
      SETTING: Reproductive Medicine Center, First Affiliated Hospital of Wenzhou
      Medical College, People's Republic of China. PATIENT(S): 62 women with polycystic
      ovary syndrome (PCOS) undergoing IVM treatment. INTERVENTION(S): Immature oocytes
      were retrieved from unstimulated ovaries of women with PCOS. We tried three
      different culture systems in this experiment. In group A, oocytes were cultured
      in the medium containing M199 + 20% fetal bovine serum (FBS) + 75 mIU/mL
      recombinant follicle-stimulating hormone (FSH) + 0.5 IU/mL recombinant hCG. In
      group B, oocytes were cultured in hCG-free IVM medium (M199 + 20% FBS + 75 mIU/mL
      recombinant FSH) for 10 hours, then transferred to the same medium as used for
      group A. In group C, oocytes were cultured only in hCG-free IVM medium. After the
      oocytes had matured in vitro, fertilization and embryo transfer were performed.
      MAIN OUTCOME MEASURE(S): Rates of maturation, fertilization, cleavage,
      implantation, clinical pregnancy, miscarriage, and live birth. RESULT(S): For
      groups A, B, and C, the maturation rates at 32 and 48 hours were 46.02% and
      69.25%; 43.72% and 64.51%; and 51.87% and 67.51%, respectively. Relatively
      satisfactory clinical results and implantation rates were obtained in all three
      groups. No statistically significant differences among groups A, B, and C were
      found in the rates of maturation, fertilization, cleavage, implantation, clinical
      pregnancy, miscarriage, or live birth. CONCLUSION(S): The results of our study
      indicated that the addition of hCG to in vitro culture medium did not improve the
      maturation rate or development potential of immature oocytes. For the IVM and
      development of immature oocytes from women with PCOS, hCG appears to be
      unnecessary.

PMID- 17524399
TI  - Diffuse gastric carcinoid polyposis in multiple endocrine neoplasia 1 syndrome
      without hypergastrinemia.

PMID- 17524400
TI  - Balloon-catheter-assisted complete endoscopic snare resection for choledochocele
      by using double-channel duodenoscope (with videos).

PMID- 17524401
TI  - Intraperitoneal bleeding after oral double-balloon enteroscopy: a case report and
      review of the literature.

PMID- 17524402
TI  - A case of ischemic colitis associated with factor V Leiden mutation: successful
      treatment with anticoagulation.

PMID- 17524404
TI  - Increased daily handling of ovariectomized rats enhances performance on a radial
      maze task and obscures effects of estradiol replacement.
AB  - Estrogen impacts performance on tasks of learning and memory, although there are
      inconsistencies in the direction and magnitude of the reported effects.
      Contributory factors to the inconsistencies may be methodological differences
      associated with different regimens of treatment. The goal of the present
      experiment was to assess the effect of increased handling, such as that commonly
      associated with pharmacological or other experimental manipulations, on the
      ability of estrogen to influence working memory performance. Young adult rats
      were ovariectomized and implanted with capsules containing either cholesterol or
      25% estradiol diluted in cholesterol. Half of each hormone treatment group
      received standard handling, which consisted of handling required to carry out
      experimental procedures and half received increased handling, which consisted of
      standard handling as well as 2 min of additional daily handling by the
      experimenter. Animals were trained daily on a working memory task on an eight-arm
      radial maze for 24 days of acquisition and for eight additional daily trials in
      which delays of either 1 min or 3 h were imposed between the fourth and fifth arm
      choices. Animals that received increased handling exhibited significantly
      enhanced performance during acquisition and delay trials compared to those that
      received standard handling. Estradiol significantly enhanced performance during
      delay trials in animals that received standard handling but had no effect in
      animals that received increased handling. These results suggest that the amount
      of handling that animals receive as part of experimental procedures may obscure
      the memory enhancing effects of estradiol replacement on certain tasks of
      cognition.

PMID- 17524403
TI  - Endoscopic treatment of large superficial colorectal tumors: a case series of 200
      endoscopic submucosal dissections (with video).
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as a minimally
      invasive treatment for early gastric cancer; however, it is not widely used in
      the colorectum because of its technical difficulty. OBJECTIVE: To determine the
      feasibility of using ESD for treating large superficial colorectal tumors and to
      evaluate the clinical outcome. DESIGN AND SETTING: Case series conducted at the
      National Cancer Center Hospital in Tokyo. PATIENTS: A total of 198 consecutive
      patients were treated for 200 lesions. INTERVENTIONS: Procedures were performed,
      before July 2004, by using a monopolar needle knife or an insulation-tipped knife
      (IT knife). After July 2004, the procedures were performed by using a bipolar
      needle knife or an IT knife. After injection of glycerol and sodium hyaluronate
      acid into the submucosal (sm) layer, a circumferential incision was made and sm
      dissection was performed endoscopically. MAIN OUTCOME MEASUREMENTS: The en bloc
      resection rate was 84% and the curative resection rate was 83%. RESULTS: Among
      the 200 ESDs, 51 involved tubular adenomas, 99 intramucosal cancers, 22 minute sm
      cancers, and 28 sm deep cancers. The median operation time was 90 minutes, and
      the mean size of resected specimens was 38 mm (range, 20-150 mm). Perforations
      occurred in 10 cases (5%) and postoperative bleeding in 4 cases (2%), but only 1
      perforation case needed emergency surgery, because endoscopic clipping was
      ineffective. LIMITATIONS: No long-term outcome data yet. CONCLUSIONS: ESD is a
      feasible technique for treating large superficial colorectal tumors, because it
      provides a higher en bloc resection rate and is less invasive than surgical
      resection.

PMID- 17524405
TI  - What Greek mothers know about evaluation and treatment of fever in children: an
      interview study.
AB  - BACKGROUND: Fever is one of the most common symptoms in childhood. Mothers'
      insufficient knowledge about its evaluation and treatment frequently leads to
      excessive fear and anxiety. OBJECTIVES: To explore mothers' knowledge concerning
      management of fever in their children, at home. DESIGN: Descriptive,
      correlational. SETTINGS: An emergency department of a pediatric hospital.
      PARTICIPANTS: A total of 327 mothers with febrile children randomly selected in
      the waiting room. METHODS: Data collection was based on interviews by using a
      questionnaire which was specifically developed for this study. RESULTS: Almost
      one out of three mothers (32.4%) evaluated fever as a temperature between 37-38
      degrees C and the 38.1% of them considered that side effects could be a result of
      these temperatures. The majority of the mothers (73.7%) administered antipyretics
      at body temperatures of 37-38.5 degrees C, usually without a medical instruction
      (49.2%). Younger mothers with lower education levels and those who admitted to
      hospital for the first time with children less than 12 months of age showed the
      poorest level of Knowledge about fever evaluation and treatment. CONCLUSIONS:
      Educational interventions by health care professionals aiming at educating young
      mothers with a low educational level and those with a child younger than 12
      months old who seek medical attention at hospital, for the first time, are needed
      to dispel misconceptions about fever and to promote the appropriate management of
      the febrile child.

PMID- 17524406
TI  - Re-mapping client journeys and professional identities: a review of the
      literature on clinical pathways.
AB  - OBJECTIVES: To explore the growing use of clinical pathways by nurses and
      midwives, their impact on client care, and the potential consequences of
      widespread pathway utilisation for the professional identity and knowledge base
      of nursing and midwifery. METHODS: A keyword search was performed within CINAHL
      and PubMed for the period 1995-2006 to identify relevant material, and article
      bibliographies were examined to identify relevance references. Thirty-nine
      publications were selected for inclusion in the analysis on the basis that they
      offered the most original account of the development of pathways or their
      effectiveness, or because they provided useful theoretical concepts. A thematic
      analysis of the selected articles was undertaken. RESULTS: The review identified
      four main themes: the multiple aims of clinical pathways; the process of initial
      development; pathway implementation in practice, and the impacts of pathways on
      client care, professional identities, and the nature of written documentation.
      Clinical pathways have multiple aims, including standardising practice, levering
      external evidence into local health care work, and improving interprofessional co
      ordination. The review found limited evidence of pathways' impact on client care,
      but the existing research suggests that they may be most suitable for
      predictable, routinised surgical procedures. Key concepts, such as variance and
      audit were found to be poorly defined. Clinical pathways appear to achieve many
      of their effects at the development stage and the reshaping of professional
      interactions. CONCLUSIONS: Given their widespread adoption and valorisation as
      tools of evidence-based practice, the dearth of evidence for clinical pathways
      should raise concerns. Clinical pathways may have significant impacts on nursing
      and midwifery as professions, both through redrawing professional identities and
      boundaries, and transforming the ways in which nurses and midwives document care.
      The impact of standardised pathways on professional ideologies which emphasise
      individualised care, and clinical autonomy will require long-term programmes of
      research.

PMID- 17524407
TI  - Thoracic aorta atherosclerosis burden index predicts coronary artery disease in
      patients undergoing transesophageal echocardiography.
AB  - AIMS: The severity of thoracic aortic atherosclerosis (TAA) is associated with
      the extent of coronary artery disease (CAD). The aim of this study is to
      quantitative this relationship by developing a novel atherosclerotic index.
      METHODS AND RESULTS: Two hundred and forty six consecutive patients underwent
      transesophageal echocardiography (TEE) and coronary angiography. A grading system
      was used to define the extent of TAA for individual segment of the thoracic
      aorta. TAA burden index (TAABI) was defined as the sum of the grading for each
      segment. Of the derived values TAABI had the greatest specificity and sensitivity
      in predicting CAD. A TAABI of greater than 6 was associated with 16-fold increase
      in the probability of CAD with a specificity of 88% and a sensitivity of 81%. The
      positive predictive value was 77% and the negative predictive value 90%.
      CONCLUSION: A TAABI value of greater than 6 accurately predicts the presence of
      CAD. Patients with no or mild TAA are at low risk of having angiographically
      significant CAD.

PMID- 17524408
TI  - Markers of vascular disease do not differ in black and white hemodialysis
      patients despite a different risk profile.
AB  - Increased aortic stiffness, as measured by pulse wave velocity (PWV) and
      augmentation index (Aix), and vascular calcification have been associated with an
      unfavourable cardiovascular outcome in hemodialysis patients. However, the
      majority of data have been published in white patients and epidemiological data
      are discordant on the fate of patients of different races. In this cross
      sectional study we measured PWV and Aix by applanation tonometry and coronary
      artery and thoracic aorta calcium score (CAC and AoC) by electron beam tomography
      (EBT) in 81 Blacks and 61 Whites on maintenance hemodialysis. Vascular stiffness
      measurements and EBT scans were performed within a week of each other. There was
      no difference between races in age, systolic blood pressure or gender
      distribution. Blacks had a more frequent history of hypertension (100% versus
      89%; P=0.002), lower prevalence of dyslipidemia (30% versus 66%; P<0.001), higher
      PTH levels (geometric mean 607 pg/ml versus 245 pg/ml; P=0.039), received calcium
      based phosphate binders less frequently (37% versus 60%, P=0.007) and calcium
      antagonists more frequently than Whites (54% versus 28%; P=0.003). Nonetheless,
      the unadjusted and risk adjusted PWV and Aix, as well as CAC and AoC were not
      statistically different between races. In this dialysis cohort there was no
      difference in markers of vasculopathy between black and white patients despite
      differences in baseline clinical characteristics. Epidemiological data from the
      general population indicate that Blacks have lower calcium scores and stiffer
      vessels than Whites. Some studies in the renal populations suggest a better and
      others a similar survival of Blacks and Whites on hemodialysis. Our findings
      raise the important question of the prognostic significance of markers of
      vasculopathy in patients of different races and with different risk profiles.

PMID- 17524409
TI  - Micro-computed tomography prediction of biomechanical strength in murine
      structural bone grafts.
AB  - Correlating massive bone graft strength to parameters derived from non-invasive
      imaging is important for pre-clinical and clinical evaluation of therapeutic
      adjuvants designed to improve graft repair. Towards that end, univariate and
      multivariate regression between measures of graft and callus geometry from micro
      CT imaging and torsional strength and rigidity were investigated in a mouse
      femoral graft model. Four millimeter mid-diaphyseal defects were grafted with
      live autografts or processed allografts and allowed to heal for 6, 9, 12, or 18
      weeks. We observed that allograft remodeling and incorporation into the host
      remained severely impaired compared to autografts mainly due to the extent of
      callus formation around the graft, the rate and extent of the graft resorption,
      and the degree of union between the graft and host bone as judged by post
      mechanical testing analysis of the mode of failure. The autografts displayed
      greater ultimate torque and torsional rigidity compared to the allografts over
      time. However the biomechanical properties of allografts were equivalent to
      autografts by 9 weeks but significantly decreased at 12 and 18 weeks.
      Multivariate regression analysis demonstrated significant statistical
      correlations between combinations of the micro-CT parameters (graft and callus
      volume and cross-sectional polar moment of inertia) with the measured ultimate
      torque and torsional rigidity (adjusted R(2)=44% and 50%, respectively). The
      statistical correlations approach used in this mouse study could be useful in
      guiding future development of non-invasive predictors of the biomechanical
      properties of allografts using clinical CT.

PMID- 17524410
TI  - Fast separation liquid chromatography-tandem mass spectrometry for the
      confirmation and quantitative analysis of avermectin residues in food.
AB  - A new residue analytical method for the confirmation and quantification of
      avermectin residues in food is described in this article. This method allows a
      fast analysis for the determination of avermectin residues, abamectin (ABM),
      ivermectin (IVM), emamectin benzoate (EMA) and doramectin (DOR) by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Separation was performed
      using a short column of 1.8 microm particle size. The hybrid quadrupole/linear
      ion trap (QqQ(LIT)) system via the linearly accelerating (LINAC) high-pressure
      collision cell, allows the MS detection in multiple reaction monitoring (MRM)
      mode operating in fast scan acquisition times. The effect of reduced dwell times
      on mass spectral quality and sensitivity is evaluated in this study. For
      quantitative purposes, the influence of dwell time on S/N ratio and peak area was
      observed. ABM, IVM, EMA and DOR show an increased trend of peak area and S/N
      ratio, when dwell times are of 50 ms against 10-20 ms, suited when the number of
      compounds to be analyzed is higher. The sensitivity achieved by using the LC
      MS/MS system is enough for the confirmation of avermectin residues in the
      selected commodities (salmon muscle and pepper) at trace concentration levels
      (sub-microg/kg and microg/kg) and therefore a sample pre-concentration step was
      not necessary. The instrumental limits of quantification (ILQ) are in the range
      of 0.15-5 ppb. Samples were extracted by solid-liquid extraction (SLE) procedure
      using acetonitrile, and cleaned-up using alumina. The average recoveries obtained
      were acceptable (80-95%). The calibration curves were linear over the working
      range from ILQs to 500 microg/kg. For the quantitative analysis, matrix-matched
      calibration and dilution of SLE extracts was proven as reliable alternative to
      compensate matrix-effects and for its feasible application in routine analysis.

PMID- 17524411
TI  - Corrosion problem in headspace gas chromatography with phase reaction conversion
      technique.
AB  - This paper reports a corrosion problem in the headspace sampling needle when
      using a phase reaction conversion headspace gas chromatographic method in Agilent
      headspace auto-sampler. The examination by microscopy shows that corrosion mainly
      takes place on the surface of the outer wall of the needle that is exposed to the
      air during each headspace sampling. Since it was proven that the helium flushing
      is effective in minimizing the pit type of corrosion on the stainless needle
      material, a custom-made surface flushing device was proposed for corrosion
      inhibition.

PMID- 17524412
TI  - Generalizing a two-conformation model for describing salt and temperature effects
      on protein retention and stability in hydrophobic interaction chromatography.
AB  - A two-conformation adsorption model that includes the effects of salt
      concentration and temperature on both stability and adsorption has been developed
      to describe the effects of secondary protein unfolding on hydrophobic interaction
      chromatography (HIC). The model has been applied to a biotech protein and to beta
      lactoglobulin on Phenyl Sepharose 6FF low sub HIC media. Thermodynamic property
      models for adsorption and protein stability with parameters obtained from
      experimental chromatographic data successfully describe observed chromatographic
      behavior over ranges of temperature and salt concentration, provide predictions
      of distribution among different conformers, and give a basis for calculating
      trends in retention strength and stability with changing conditions, that might
      prove useful in HIC process development.

PMID- 17524413
TI  - Determination of Bitter Orange alkaloids in dietary supplements standard
      reference materials by liquid chromatography with ultraviolet absorbance and
      fluorescence detection.
AB  - Four adrenergic amines [synephrine, octopamine, tyramine, and n-methyltyramine]
      were determined in a variety of Bitter Orange containing dietary supplements. Two
      extraction techniques were evaluated in detail: Soxhlet extraction and sonication
      extraction. A liquid chromatographic separation using a reversed-phase C(18)
      stationary phase and the ion-pairing reagent sodium dodecyl sulfate was developed
      to separate the Bitter Orange alkaloids. Ultraviolet absorbance detection at 220
      nm and fluorescence detection with excitation at 273 nm and emission at 304 nm
      were used for the alkaloid detection. The method described was used for the
      assignment of the levels of the predominant alkaloids in three candidate standard
      reference materials containing Bitter Orange.

PMID- 17524414
TI  - Tetrad effect in the adsorption of the lanthanides on zeolite Y.
AB  - The adsorption of the lanthanides (except for Pm) on the zeolite Y was
      investigated under various solution conditions of nitrate ion concentration ([NO(
      )(3)]: 0.001-2 mol/dm(3)) and total lanthanide concentration (from 0.0001 to
      0.001 mol/dm(3)). The solutions of the lanthanide nitrates were equilibrated with
      the zeolite samples at 296 K. The concentrations of lanthanides in the initial
      and equilibrium solutions were determined by means of spectrophotometrical method
      with Arsenazo III reagent and distribution constants K(d) of the lanthanides
      between aqueous and zeolite phases were calculated. The evident concave tetrad
      effect in the change of logK(d) values (nitrate concentrations 0.4-2 mol/dm(3))
      within the lanthanide series was noticed and an attempt at its explanation
      through the comparison of covalence in LnO bonds existing in triple bond
      AlO(1/3Ln)Si triple bond species in the zeolite phase and in Ln(NO(3))(2+)
      complexes forming in the aqueous phase was presented. The weak convex tetrad
      effect for equilibrium nitrate concentrations 0.001-0.32 mol/dm(3), manifesting
      in the change of logK(d) values and in the alteration of logK (adsorption
      constants), is evidence of the complexation of the tripositive lanthanide ions by
      the oxygens originating both from water molecules and from the zeolite framework.

PMID- 17524415
TI  - Agglomeration of alumina submicronparticles by silica nanoparticles: application
      to processing spheres by colloidal route.
AB  - In aqueous media, heterocoagulation between submicronic alumina (400 nm) and
      nanometric silica (25 nm) leads to the adsorption of silica on the alumina
      surface. By controlling the coverage rate of alumina particles, this adsorption
      destabilizes the suspension that leads to a very porous network of agglomerated
      particles. This work shows that the structure is all the more open as the density
      of charge carried by the two oxides is high and the ionic strength in the
      suspension low. From such a flocculated suspension, a new colloidal process to
      fabricate ceramic spheres is proposed which is based on a size increase of
      agglomerates. Under a controlled rotation of the vessel, electrostatic attraction
      between the surface charges of opposite polarity induces a size increase of
      agglomerates until the formation of spheres occurs. It has been shown that the
      mechanism of growth is poisoned by species adsorbed such as ions. Nevertheless,
      this new process proves very promising because it leads to a narrow size
      distribution of spheres by colloidal way, which can be subsequently consolidated
      by sintering, with a smooth surface.

PMID- 17524416
TI  - What determines protein folding type? An investigation of intrinsic structural
      properties and its implications for understanding folding mechanisms.
AB  - Protein folding experiments demonstrate that the folding behaviors of many
      proteins can be roughly classified into two types: two-state kinetics and multi
      state kinetics. Although the two types of protein folding kinetics have been
      observed for a long time, what determines the folding type of a protein is still
      largely unclear. The present work performed a comparative study based on a
      dataset of 43 two-state and 42 multi-state folders at different levels of
      proteins' intrinsic properties from the simplest sequence length to native
      structure topology. The results show that protein's amino acids composition and
      the long-range interaction-based topological complexity rather than secondary
      structure contents are the major determinants of protein folding type.
      Furthermore, a sequence-based folding type prediction achieved an accuracy of
      more than 80%. These findings implicate that there is no clear boundary between
      secondary and tertiary structure formation during the protein folding process and
      support the existence of a continuum of folding mechanism between the two ends of
      hierarchic and nucleation folding scenarios.

PMID- 17524417
TI  - CENP-A-containing nucleosomes: easier disassembly versus exclusive centromeric
      localization.
AB  - CENP-A is a histone variant that replaces conventional H3 in nucleosomes of
      functional centromeres. We report here, from reconstitutions of CENP-A- and H3
      containing nucleosomes on linear DNA fragments and the comparison of their
      electrophoretic mobility, that CENP-A induces some positioning of its own and
      some unwrapping at the entry-exit relative to canonical nucleosomes on both 5 S
      DNA and the alpha-satellite sequence on which it is normally loaded. This steady
      state unwrapping was quantified to 7(+/-2) bp by nucleosome reconstitutions on a
      series of DNA minicircles, followed by their relaxation with topoisomerase I. The
      unwrapping was found to ease nucleosome invasion by exonuclease III, to hinder
      the binding of a linker histone, and to promote the release of an H2A-H2B dimer
      by nucleosome assembly protein 1 (NAP-1). The (CENP-A-H4)2 tetramer was also more
      readily destabilized with heparin than the (H3-H4)2 tetramer, suggesting that
      CENP-A has evolved to confer its nucleosome a specific ability to disassemble.
      This dual relative instability is proposed to facilitate the progressive
      clearance of CENP-A nucleosomes that assemble promiscuously in euchromatin,
      especially as is seen following CENP-A transient over-expression.

PMID- 17524418
TI  - Evolved to be active: sulfate ions define substrate recognition sites of CK2alpha
      and emphasise its exceptional role within the CMGC family of eukaryotic protein
      kinases.
AB  - CK2alpha is the catalytic subunit of protein kinase CK2 and a member of the CMGC
      family of eukaryotic protein kinases like the cyclin-dependent kinases, the MAP
      kinases and glycogen-synthase kinase 3. We present here a 1.6 A resolution
      crystal structure of a fully active C-terminal deletion mutant of human CK2alpha
      liganded by two sulfate ions, and we compare this structure systematically with
      representative structures of related CMGC kinases. The two sulfate anions occupy
      binding pockets at the activation segment and provide the structural basis of the
      acidic consensus sequence S/T-D/E-X-D/E that governs substrate recognition by
      CK2. The anion binding sites are conserved among those CMGC kinases. In most
      cases they are neutralized by phosphorylation of a neighbouring threonine or
      tyrosine side-chain, which triggers conformational changes for regulatory
      purposes. CK2alpha, however, lacks both phosphorylation sites at the activation
      segment and structural plasticity. Here the anion binding sites are functionally
      changed from regulation to substrate recognition. These findings underline the
      exceptional role of CK2alpha as a constitutively active enzyme within a family of
      strictly controlled protein kinases.

PMID- 17524419
TI  - Crystal structures of tRNA-guanine transglycosylase (TGT) in complex with novel
      and potent inhibitors unravel pronounced induced-fit adaptations and suggest
      dimer formation upon substrate binding.
AB  - The bacterial tRNA-guanine transglycosylase (TGT) is a tRNA modifying enzyme
      catalyzing the exchange of guanine 34 by the modified base preQ1. The enzyme is
      involved in the infection pathway of Shigella, causing bacterial dysentery. As no
      crystal structure of the Shigella enzyme is available the homologous Zymomonas
      mobilis TGT was used for structure-based drug design resulting in new, potent,
      lin-benzoguanine-based inhibitors. Thorough kinetic studies show size-dependent
      inhibition of these compounds resulting in either a competitive or non
      competitive blocking of the base exchange reaction in the low micromolar range.
      Four crystal structures of TGT-inhibitor complexes were determined with a
      resolution of 1.58-2.1 A. These structures give insight into the structural
      flexibility of TGT necessary to perform catalysis. In three of the structures
      molecular rearrangements are observed that match with conformational changes also
      noticed upon tRNA substrate binding. Several water molecules are involved in
      these rearrangement processes. Two of them demonstrate the structural and
      catalytic importance of water molecules during TGT base exchange reaction. In the
      fourth crystal structure the inhibitor unexpectedly interferes with protein
      contact formation and crystal packing. In all presently known TGT crystal
      structures the enzyme forms tightly associated homodimers internally related by
      crystallographic symmetry. Upon binding of the fourth inhibitor the dimer
      interface, however, becomes partially disordered. This result prompted further
      analyses to investigate the relevance of dimer formation for the functional
      protein. Consultation of the available TGT structures and sequences from
      different species revealed structural and functional conservation across the
      contacting residues. This suggests that bacterial and eukaryotic TGT could
      possibly act as homodimers in catalysis. It is hypothesized that one unit of the
      dimer performs the catalytic reaction whereas the second is required to recognize
      and properly orient the bound tRNA for the catalytic reaction.

PMID- 17524420
TI  - An EM view of the FokI synaptic complex by single particle analysis.
AB  - FokI is a type IIS restriction endonuclease that recognizes the 5'-GGATG-3'
      sequence and cleaves non-specifically at 9 and 13 base-pairs away on the top and
      bottom strands, respectively, to produce a 5' overhang. FokI is a bipartite
      endonuclease with separate recognition and cleavage domains. Because of its
      bipartite nature, FokI has received considerable interest in generating chimeric
      nucleases for use in biotechnology, and recently as possible therapeutic agents
      in gene therapy by initiating homologous gene recombination and repair. Here we
      show, using single-particle electron microscopic studies, that the FokI active
      complex prefers a single conformation in which the subunits are arranged in a
      doughnut shape complex with protein-protein and possibly protein-DNA interactions
      stabilizing the cleavage complex. Our electron microscopy (EM) model provides new
      insights into the activation mechanism of FokI and how non-specific cleavage is
      avoided.

PMID- 17524421
TI  - Computational characterization of structural role of the non-active site mutation
      M36I of human immunodeficiency virus type 1 protease.
AB  - A prominent characteristic of human immunodeficiency virus type 1 (HIV-1) is its
      high genetic variability, which generates diversity of the virus and often causes
      a serious problem of the emergence of drug-resistant mutants. Subtype B HIV-1 is
      dominant in advanced countries, and the mortality rate due to subtype B HIV-1 has
      been decreased during the past decade. In contrast, the number of patients with
      non-subtype B viruses is still increasing in developing countries. One of the
      reasons for the prevalence of non-subtype B viruses is lack of information about
      the biological and therapeutic differences between subtype B and non-subtype B
      viruses. M36I is the most frequently observed polymorphism in non-subtype B HIV-1
      proteases. However, since the 36th residue is located at a non-active site of the
      protease and has no direct interaction with any ligands, the structural role of
      M36I remains unclear. Here, we performed molecular dynamics (MD) simulations of
      M36I protease in complex with nelfinavir and revealed the influence of the M36I
      mutation. The results show that M36I regulates the size of the binding cavity of
      the protease. The reason for the rare emergence of D30N variants in non-subtype B
      HIV-1 proteases was also clarified from our computational analysis.

PMID- 17524423
TI  - The supramolecular assemblies of voltage-dependent anion channels in the native
      membrane.
AB  - Voltage-dependent anion channels (VDACs) are major constituents of the outer
      mitochondrial membrane (OMM). These primary transporters of nucleotides, ions and
      metabolites mediate a substantial portion of the OMM molecular traffic. To study
      the native supramolecular organization of the VDAC, we have isolated,
      characterized and imaged OMMs from potato tubers. SDS-PAGE and mass spectrometry
      of OMMs revealed the presence of the VDAC isoforms POM34 and POM36, as well as
      the translocase of the OMM complex. Tubular two-dimensional crystals of the VDAC
      spontaneously formed after incubation of OMMs for two to three months at 4
      degrees C. Transmission electron microscopy revealed an oblique lattice and unit
      cells housing six circular depressions arranged in a hexagon. Atomic force
      microscopy of freshly isolated OMMs demonstrated (i) the existence of monomers to
      tetramers, hexamers and higher oligomers of the VDAC and (ii) its spatial
      arrangement within the oligomers in the native membrane. We discuss the
      importance of the observed oligomerization for modulation of the VDAC function,
      for the binding of hexokinase and creatine kinase to the OMM and for mitochondria
      mediated apoptosis.

PMID- 17524422
TI  - Defective signal joint recombination in fanconi anemia fibroblasts reveals a role
      for Rad50 in V(D)J recombination.
AB  - V(D)J recombination of immunoglobulin loci is dependent on the immune cell
      specific Rag1 and Rag2 proteins as well as a number of ubiquitously expressed
      cellular DNA repair proteins that catalyze non-homologous end-joining of DNA
      double-strand breaks. The evolutionarily conserved Rad50/Mre11/Nibrin protein
      complex has a role in DNA double-strand break-repair, suggesting that these
      proteins, too, may participate in V(D)J recombination. Recent findings
      demonstrating that Rad50 function is defective in cells from patients afflicted
      with Fanconi anemia provide a possible mechanistic explanation for previous
      findings that lymphoblasts derived from these patients exhibit subtle defects in
      V(D)J recombination of extrachromosomal plasmid molecules. Here, we describe a
      series of findings that provide convincing evidence for a role of the Rad50
      protein complex in V(D)J recombination. We found that the fidelity of V(D)J
      signal joint recombination in fibroblasts from patients afflicted with Fanconi
      anemia was reduced by nearly tenfold, compared to that observed in fibroblasts
      from normal donors. Second, we observed that antibody-mediated inhibition of the
      Rad50, Mre11, or Nibrin proteins reduced the fidelity of signal joint
      recombination significantly in wild-type cells. The latter finding was somewhat
      unexpected, because signal joint rejoining in cells from patients with Nijmegen
      breakage syndrome, which results from mutations in the Nibrin gene, occurs with
      normal fidelity. However, introduction of anti-Nibrin antibodies into these cells
      reduced the fidelity of signal joint recombination dramatically. These data
      reveal for the first time a role for the Rad50 complex in V(D)J recombination,
      and demonstrate that the protein product of the disease-causing allele
      responsible for Nijmegen breakage syndrome encodes a protein with residual DNA
      double-strand break repair activity.

PMID- 17524424
TI  - Intracranial large artery disease among OCSP subtypes in ethnic South Asian
      ischemic stroke patients.
AB  - The site of vascular stenosis correlates well with the Oxfordshire Community
      Stroke Project (OCSP) classification among Caucasians, but not among ethnic
      Chinese patients. We prospectively studied 205 consecutive ethnic South Asian
      ischemic stroke patients to investigate the prevalence of intracranial large
      artery disease determined by transcranial color-coded doppler and magnetic
      resonance angiography among OCSP subtypes. The distribution of OCSP subtypes was
      7% total anterior circulation infarction (TACI), 17% partial anterior circulation
      infarction (PACI), 14% posterior circulation infarction (POCI) and 62% lacunar
      infarction (LACI). Significant intracranial large artery disease was common among
      all OCSP subtypes; 79% with TACI, 47% PACI, 65% POCI and 44% LACI. This is
      similar to ethnic Chinese data and is likely due to the predominance of
      intracranial disease over extracranial disease. Clinical axioms using OSCP
      subtypes based on Caucasian data may be misleading if applied to ethnic South
      Asians.

PMID- 17524425
TI  - ICH aspiration and thrombolysis.
AB  - Intracerebral hemorrhage (ICH) is associated with the highest mortality among all
      forms of stroke. Evolution in the medical management of ICH has not improved
      patient outcomes while the results of conventional surgery have generally been
      disappointing. Minimally invasive surgery (MIS) using stereotactic clot
      aspiration followed by clot lysis is gaining credibility as an alternative
      management strategy. We review the published data on this methodology in the
      treatment of ICH.

PMID- 17524426
TI  - Capit timed tests quantify age-related motor decline in normal subjects.
AB  - Slowing of motor performance in human aging is a well demonstrated clinical
      observation. Age-related motor decline has been also confirmed in animal models
      including rodents and non human primates. We studied the motor performance of 60
      normal subjects (age: 20-87). Motor study included the four timed tests (TT)
      recommended in CAPIT protocol: pronation-supination (PS), finger dexterity (FD),
      movement between two points (MTP) or tapping, and walking test (WT). Finally we
      compared normal controls with a group of 30 patients with Parkinson's disease
      (PD) of similar age. Age inversely correlated with TT performance in normal
      subjects (for PS, r:0.33, p<0.01; FD, r:0.44, p<0.0005; MTP, r:0.51, p<0.0001;
      WT, r:0.59, p<0.0001, Pearson). Our results confirm that motor performance
      (measured with CAPIT TT) deteriorates linearly with age. Simple tasks, such as
      CAPIT TT can help to study and quantify age-related motor decline.

PMID- 17524427
TI  - A novel in-frame deletion in the CAV3 gene in a Korean patient with rippling
      muscle disease.
AB  - Rippling muscle disease (RMD) is a rare form of myopathy that is characterized by
      percussion-induced rapid muscle contractions, muscle mounding, and rippling.
      Recently a caveolin-3 gene (CAV3) mutation was identified in patients suffering
      from autosomal dominant RMD. We encountered a Korean male patient with RMD who
      had suffered from muscle stiffness for 3 years. Mutation analysis of the CAV3
      gene revealed the patient to be heterozygous for a novel in-frame deletion
      mutation (c.307_312delGTGGTG; Phe103_Phe104del). Further analysis of his family
      members showed that his mother and elder sister also have the same mutation. To
      the best of our knowledge, this is the first report of genetically confirmed RMD
      in Korea.

PMID- 17524428
TI  - Semi-discrete host-parasitoid models.
AB  - Arthropod host-parasitoid interactions constitute a very important class of
      consumer resource dynamics. Discrete-time models are a tradition for such
      interactions and are characterized by an updating function, which relates the
      population densities at a fixed date in one year to those at the same date in the
      previous year. Previous workers have investigated the effects of functional
      response and density dependence on the stability of the host-parasitoid
      interaction by heuristically incorporating them in the updating function. Such an
      approach ignores the effects of population changing continuously within a year
      due to different processes (for example intraspecific competition, mortality from
      parasitism) that may act simultaneously. Their cumulative effect on the updating
      function is not obvious and a more systematic methodology is needed. This paper
      uses a hybrid approach to formulate the updating function. This is done by
      modeling the dynamics of various within-year processes in continuous-time, and
      reproduction as a discrete event. Using this formalism we derive results
      connecting the stability of the host-parasitoid interaction with different forms
      of density dependence and the form of the functional response. The latter results
      contradict previous conclusions from heuristically formulated models, and
      illustrate the need for such a hybrid approach in discrete-time host-parasitoid
      theory.

PMID- 17524429
TI  - A computational model that links non-periodic vasomotion to enhanced oxygenation
      in skeletal muscle.
AB  - We propose a model of a capillary network in which chaotic capillary activity is
      crucial for efficient oxygenation of a muscle fiber. Tissue oxygenation by
      microcirculation is controlled by a complex pattern of opening and closing of
      precapillary sphincters, a phenomenon known as vasomotion. We model the
      individual precapillary sphincter as a non-linear oscillator that exhibits
      perfectly periodic vasomotion in isolation. The precapillary sphincters
      surrounding an active fiber are considered as a network; specific modes of
      interaction within this network result in complex patterns of vasomotion. In our
      model, efficient oxygenation of the fiber depends crucially on the mode of
      interaction among the vasomotions of the individual capillaries. Network
      interactions that lead to chaotic vasomotion are found to be essential for
      meeting the tissue oxygen demands precisely. Interactions that cause regular
      rhythmic patterns of vasomotion fail to meet oxygenation demands accurately.

PMID- 17524430
TI  - Estrogen induces endothelial progenitor cells proliferation and migration by
      estrogen receptors and PI3K-dependent pathways.
AB  - Estrogen induces endothelial progenitor cells (EPCs) migration and proliferation,
      which may serve as a potential target for coronary artery disease, but the
      mechanisms are unclear. We hypothesized that estrogen receptors (ERs) and
      phosphatidylinositol 3-kinase (PI3K) signaling pathway, which represent
      particularly important roles of action for estrogen, may contribute to estrogen
      induced EPCs migration and proliferation. Bone marrow mononuclear cells (MNCs)
      were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with
      growth factors as previously described. A total of 87.32+/-5.13% of adherent
      cells showed uptake of acetylated low-density lipoprotein and lectin binding.
      Immunostaining and fluorescence activated cell sorting confirmed the endothelial
      progenitor phenotype. RT-PCR, immunocytochemistry staining and Western blot
      demonstrated expression of ERs. Exposure to 17beta-estradiol significantly
      improved EPCs migration and proliferation. Those effects were blocked by
      pretreatment with the pharmacological PI3K blockers LY294002 (1 h, 10 micromol/L)
      and ICI-182780 (1 h, 10 micromol/L), a specific estrogen receptor antagonist,
      which show involvement of estrogen receptors and PI3K pathway. These results
      suggest that estrogen induces EPCs migration and proliferation via ERs and PI3K
      pathway which provided a novel insight and treatment strategy of vascular
      biology.

PMID- 17524431
TI  - [Pituitary carcinoma. Anatomic and clinical features of cases reported in
      literature].
AB  - BACKGROUND AND PURPOSE: Pituitary gland tumors that became aggressive, implying
      adjacent bone structure and the brain as metastases outside of the cranial box,
      are referred to as pituitary carcinomas. METHODS: We reviewed 67 cases reported
      in the literature [44 corticotropic pituitary tumors, 11 PRL tumors, 3 GH tumors,
      1 TSH tumor, 3 gonadotropic cell tumors and 5 non-functioning tumors]. RESULTS:
      The corticotropic tumors occurred in 23 female and 15 males. Signs of
      hypercorticism were characteristic: generalized melanosis before adrenalectomy
      (N=1); headache (N=1); altered visual (N=1); diabetes insipidus (N=1); amenorrhea
      (N=1); Cushing syndrome (N=2); weight loss (N=1); refractory hypokaliemic
      alkalosis (N=1); diabetes mellitus (N=1); hypertension (N=1). ACTH, beta
      lipotrophin, betaendorphin, alphamelano-stimulating hormone, CRH, and beta-gamma
      MSH were contributive while ultrastructural microscopy provided little
      information, as did an equimolar Lph/ACTH ratio. The possible association of
      prolactin tumors with corticotrophin forms has been underlined. The
      characteristic feature is a time interval from the initial diagnosis of adenoma
      to that of cancer, which has ranged from 0.3 to 18 years (mean: 6.6 years;
      median: 5.0 years). CONCLUSION: Corticotropic tumors resistance to high-dose
      medical treatment are usually aggressive tumors with a risk of recurrence after
      surgical treatment or even radiotherapy with the risk of metastases. GH tumors
      appear to predominate although it is known that these cancers can develop in
      association with corticotrophin cancers or with prolactin cell tumors.

PMID- 17524432
TI  - Hemispheric differences in processing dichotic meaningful and non-meaningful
      words.
AB  - Classic dichotic-listening paradigms reveal a right-ear advantage (REA) for
      speech sounds as compared to non-speech sounds. This REA is assumed to be
      associated with a left-hemisphere dominance for meaningful speech processing.
      This study objectively probed the relationship between ear advantage and
      hemispheric dominance in a dichotic-listening situation, using event-related
      potentials (ERPs). The mismatch negativity (MMN) and a late negativity (LN) were
      measured for bisyllabic meaningful words and non-meaningful pseudowords, which
      differed in their second syllable. Eighteen normal-hearing listeners were
      presented with a repeating diotic standard ([beI-gi:] or [leI-gi:]) and an
      occasional dichotic deviant (a standard presented to one ear and a deviant [beI
      bi:], [beI-di:], [leI-bi:] or [leI-di:] presented to the opposite ear). As
      predicted there was a REA for meaningful words compared to non-meaningful words.
      Also, dipole source analysis suggested that dipole strength was stronger in the
      left than the right cortical region for meaningful words. However, there were
      differences in response within meaningful words as well as between meaningful and
      non-meaningful words which may be explained by the characteristics of embedded
      words and the position-specific probability of phoneme occurrence in words.

PMID- 17524433
TI  - Behavioral and biochemical effects of various food-restriction regimens in the
      rats.
AB  - In this paper we describe the effects of six different food restriction (FR)
      regimens on amphetamine (AMPH)-induced locomotor and nonlocomotor activities in
      male rats. Changes in serum corticosterone (CORT), insulin and glucose levels
      were also examined. Each regimen was implemented through different daily food
      allowance (50%, 25% and 12.5% of the daily food intake, referred to as 50%, 75%
      and 87.5% FR groups, respectively) and by a specific feeding regimen - either
      every day (ED) or every other day (EOD). AMPH injection led to a significant
      increase of locomotor activity in all rats subjected to FR compared to ad libitum
      fed rats. A significant increase of nonlocomotor activity was observed only in
      the 75% FR and 87.5% FR groups. The serum CORT levels were significantly elevated
      and the serum insulin and glucose levels were significantly decreased in all of
      the FR groups in comparison to the AL rats. The results presented in this paper
      suggest that the ED regimens produced changes in motor activity and biochemical
      parameters, which were more-or-less dependent on the degree of FR. In contrast,
      the EOD regimens induced very similar changes irrespective of the degree of FR
      degree. Our data support the possible mechanistic roles of CORT and insulin in
      the effect of FR on locomotor activity, since the most pronounced increase of
      serum CORT and more pronounced decrease in serum insulin concentration was
      observed in the groups that also exhibited the highest locomotor activities.

PMID- 17524434
TI  - Sleep and EEG profile in neonatal hippocampal lesion model of schizophrenia.
AB  - Sleep architecture, EEG power pattern and locomotor activity were investigated in
      a putative animal model of schizophrenia. The model was prepared by excitotoxic
      damage of the ventral hippocampus on postnatal day 7 (PD 7), after which
      locomotor activity and electroencephalographic (EEG) sleep profile were compared
      between lesioned and sham operated animals respectively, at prepuberty (postnatal
      day PD 35) and postpuberty (PD 56). An enhancement of locomotor activity was
      observed in lesioned adult PD 56, but not in juvenile PD 35 rats. Spontaneous
      EEG/EMG recordings during 24 h showed no major differences between both groups at
      PD 35 and at PD 56. However, quantitative analysis of the EEG revealed an
      enhancement of power in delta (delta), theta (theta) and alpha (alpha) activities
      in lesioned animals at PD 35 during wakefulness in both light and dark phases. At
      PD 56, the power in the delta and theta bands was increased during the light and
      dark periods in both wakefulness and non-REM sleep. These findings suggest that
      ventral hippocampus lesion is not associated with disturbance of sleep
      architecture in rats, while consistent changes were observed in the dynamic of
      EEG slow wave frequency domain. Thus, the data indicate that neonatal lesion of
      ventral hippocampus did not mimic sleep abnormalities observed in schizophrenia,
      however this rodent model may model some EEG features seen in schizophrenia such
      as a frontally pronounced slowing of the slow EEG activity in delta and theta
      frequency bands.

PMID- 17524435
TI  - Obesity by choice revisited: effects of food availability, flavor variety and
      nutrient composition on energy intake.
AB  - Recent work suggested that the energy intake and weight gain of rats maintained
      on chow and 32% sucrose solution could be increased by simply offering more
      sources of sucrose [Tordoff M.G. Obesity by choice: the powerful influence of
      nutrient availability on nutrient intake. Am J Physiol 2002;282:R1536-R1539.]. In
      Experiment 1 this procedure was replicated but the effect was not: rats given one
      bottle of sucrose and five bottles of water consumed as much sucrose as those
      given five bottles of sucrose and one of water. Adding different flavors to the
      sucrose did not increase intakes further in Experiment 2. The relative potency of
      sucrose and other optional foods was studied in Experiment 3. Sucrose solution
      stimulated more overeating and weight gain than fat (vegetable shortening), and
      offering both sucrose and shortening did not generate further increases in energy
      intake. Finally, foods commonly used to produce overeating and weight gain were
      compared. Sucrose was less effective than a high-fat milk diet, and offering
      cookies in addition to the milk did not increase energy intake further. The
      nature of optional foods (nutrient composition and physical form) was markedly
      more important than the number of food sources available to the animals, and is a
      better contender as the reason for "obesity by choice".

PMID- 17524436
TI  - The rice (E)-beta-caryophyllene synthase (OsTPS3) accounts for the major
      inducible volatile sesquiterpenes.
AB  - Terpenoids serve as both constitutive and inducible defense chemicals in many
      plant species, and volatile terpenes participate in plant a indirect defense by
      attracting natural enemies of the herbivores. The rice (Oryza sativa L.) genome
      contains about 50 genes encoding putative terpene synthases (TPSs). Here we
      report that two of the rice sesquiterpene synthase genes, OsTPS3 and OsTPS13,
      encode (E)-beta-caryophyllene synthase and (E,E)-farnesol synthase, respectively.
      In vitro, the recombinant protein of OsTPS3 catalyzed formation of (E)-beta
      caryophyllene and several other sesquiterpenes, including beta-elemene and alpha
      humulene, all being components of inducible volatiles of rice plants. The
      transcript levels of OsTPS3 exhibit a circadian rhythm of fluctuation, and its
      expression was also greatly induced by methyl jasmonate (MeJA). In addition,
      expression of OsTPS3 in transgenic plants of Arabidopsis thaliana resulted in
      emitting high quantities of OsTPS3 products. We also overexpressed OsTPS3 in rice
      plants which then produced more (E)-beta-caryophyllene after MeJA treatment.
      Finally, we found that the MeJA-treated transgenic rice plants attracted more
      parasitoid wasps of Anagrus nilaparvatae than the wild-type. These results
      demonstrate that OsTPS3, an enzyme catalyzing the formation of volatile
      sesquiterpenes, plays a role in indirect defense of rice plants.

PMID- 17524437
TI  - Vacuolar compartmentation complicates the steady-state analysis of glucose
      metabolism and forces reappraisal of sucrose cycling in plants.
AB  - Steady-state stable isotope labelling provides a method for generating flux maps
      of the compartmented network of central metabolism in heterotrophic plant
      tissues. Theoretical analysis of the contribution of the vacuole to the
      regeneration of glucose by endogenous processes shows that numerical fitting of
      isotopomeric data will only generate an accurate map of the fluxes involving
      intracellular glucose if information is available on the labelling of both the
      cytosolic and vacuolar glucose pools. In the absence of this information many of
      the calculated fluxes are at best unreliable or at worst indeterminate. This
      result suggests that the anomalously high rates of sucrose cycling and glucose
      resynthesis that have been reported in earlier steady-state analyses of tissues
      labelled with (13)C-glucose precursors may be an artefact of assuming that the
      labelling pattern of extracted glucose reflected the labelling of the cytosolic
      pool. The analysis emphasises that although subcellular information can sometimes
      be deduced from a steady-state analysis without recourse to subcellular
      fractionation, the success of this procedure depends critically on the structure
      of the metabolic network. It is concluded that methods need to be implemented
      that will allow measurement of the subcellular labelling pattern of glucose and
      other metabolites, as part of the routine analysis of the redistribution of label
      in steady-state stable isotope labelling experiments, if the true potential of
      network flux analysis for generating metabolic phenotypes is to be realized.

PMID- 17524439
TI  - Effects of partial enzymic degradation of sugar beet pectin on oxidative coupling
      of pectin-linked ferulates in vitro.
AB  - Pectins were extracted from roots and petioles of sugar beet, and treated with
      alpha-arabinosidase, 1,4-beta-galactanase or polygalacturonase. They were then
      cross-linked using hydrogen peroxide and peroxidase. The effects on pectin
      molecular size were monitored by size-exclusion chromatography and viscometry. A
      decrease in apparent molecular size was observed after alpha-arabinosidase and
      polygalacturonase treatment, and all three enzymes caused a decrease in
      viscosity. The pectins were then cross-linked using hydrogen peroxide and
      peroxidase, and the effects on dehydrodiferulate formation were monitored by
      HPLC. Pretreatment with polygalacturonase caused no significant change in
      subsequent dehydrodiferulate cross-linking, while pretreatment with alpha
      arabinosidase caused a slight change in the ratios of the different
      dehydrodiferulates formed. Pretreatment with 1,4-beta-d-galactanase caused a more
      significant change in the ratios of the different dehydrodiferulates formed, and
      also greatly increased the overall recovery of total ferulates (monomers plus
      dehydrodiferulates), both in root pectin and petiole pectin. The possible effects
      of polysaccharide microstructure on the dimerisation and further polymerisation
      of pectin-linked ferulates are discussed.

PMID- 17524438
TI  - A transient isotopic labeling methodology for 13C metabolic flux analysis of
      photoautotrophic microorganisms.
AB  - Metabolic flux analysis is increasingly recognized as an integral component of
      systems biology. However, techniques for experimental measurement of system-wide
      metabolic fluxes in purely photoautotrophic systems (growing on CO(2) as the sole
      carbon source) have not yet been developed due to the unique problems posed by
      such systems. In this paper, we demonstrate that an approach that balances
      positional isotopic distributions transiently is the only route to obtaining
      system-wide metabolic flux maps for purely autotrophic metabolism. The outlined
      transient (13)C-MFA methodology enables measurement of fluxes at a metabolic
      steady-state, while following changes in (13)C-labeling patterns of metabolic
      intermediates as a function of time, in response to a step-change in (13)C-label
      input. We use mathematical modeling of the transient isotopic labeling patterns
      of central intermediates to assess various experimental requirements for
      photoautotrophic MFA. This includes the need for intracellular metabolite
      concentration measurements and isotopic labeling measurements as a function of
      time. We also discuss photobioreactor design and operation in order to measure
      fluxes under precise environmental conditions. The transient MFA technique can be
      used to measure and compare fluxes under different conditions of light intensity,
      nitrogen sources or compare strains with various mutations or gene deletions and
      additions.

PMID- 17524440
TI  - Alpha-amylase from mung beans (Vigna radiata)--correlation of biochemical
      properties and tertiary structure by homology modelling.
AB  - Alpha-amylase from germinated mung beans (Vigna radiata) has been purified 600
      fold to electrophoretic homogeneity and a final specific activity of 437 U/mg.
      SDS-PAGE of the final preparation revealed a single protein band of 46 kDa. The
      optimum pH was 5.6. The energy of activation was determined to be 7.03 kcal/mol
      in the temperature range 15-55 degrees C. Km for starch was 1.6 mg/mL in 50 mM
      sodium acetate buffer, pH 5.5. Thermal inactivation studies at 70 degrees C
      showed first-order kinetics with rate constant (k) equal to 0.005 min(-1). Mung
      bean alpha-amylase showed high specificity for its primary substrate starch.
      Addition of EDTA (10 mM) caused irreversible loss of activity. Mung bean alpha
      amylase is inhibited in a non-competitive manner by heavy metal ions, for
      example, mercury with a Ki of 110 microM. Homology modelling studies with mung
      bean alpha-amylase using barley alpha-amylases Amy 1 and Amy 2 as templates
      showed a very similar structure as expected from the high sequence identity. The
      model showed that alpha-amylase from mung beans has no sugar-binding site,
      instead it has a methionine. Furthermore, instead of two tryptophans, it has
      Val(277) and Lys(278), which are the conserved residues, important for proper
      folding and conformational stability.

PMID- 17524442
TI  - Expression and characterization of a novel reverse transcriptase of the LTR
      retrotransposon Tf1.
AB  - The LTR retrotransposon of Schizosacharomyces pombe, Tf1, has several distinctive
      properties that can be related to the unique properties of its reverse
      transcriptase (RT). Consequently, we expressed, purified and studied the
      recombinant Tf1 RT. This monomeric protein possesses all activities typical to
      RTs: DNA and RNA-dependent DNA polymerase as well as an inherent ribonuclease H.
      The DNA polymerase activity shows preference to Mn(+)(2) or Mg(+)(2), depending
      on the substrate used, whereas the ribonuclease H strongly prefers Mn(+)(2). The
      most outstanding feature of Tf1 RT is its capacity to add non-templated
      nucleotides to the 3'-ends of the nascent DNA. This is mainly apparent in the
      presence of Mn(+)(2), as is the noticeable low fidelity of DNA synthesis. In all,
      Tf1 RT has a marked infidelity in synthesizing DNA at template ends, a phenomenon
      that can explain, as discussed herein, some of the features of Tf1 replication in
      the host cells.

PMID- 17524441
TI  - Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross
      neutralizing antibodies and long-term protection.
AB  - Given the lethality of H5N1 avian influenza viruses (AIV) and the recurring
      spread from poultry to humans, an effective vaccine against H5N1 viruses may be
      needed to prevent a pandemic. We generated experimental vaccine vectors based on
      recombinant vesicular stomatitis virus (VSV) expressing the H5 hemagglutinin (HA)
      from an H5N1 virus isolated in 1997. The HA gene was expressed either from an
      attenuated wild-type VSV vector or from a single-cycle vector containing a
      deletion of the VSV G gene. We found that all of the vectors induced potent
      neutralizing antibody titers against the homologous and antigenically
      heterologous H5N1 viruses isolated in 2004 and 2005. Vaccination of mice with any
      combination of prime or prime/boost vectors provided long-lasting protection (>7
      months) against challenge with AIV, even in animals receiving a single dose of
      single-cycle vaccine. Our data indicate that these recombinants are promising
      vaccine candidates for pandemic influenza.

PMID- 17524443
TI  - Nitrogen removal from eutrophic water by floating-bed-grown water spinach
      (Ipomoea aquatica Forsk.) with ion implantation.
AB  - The aim of this study was to investigate the use of water spinach (Ipomoea
      aquatica Forsk.) with N(+) ion-beam implantation for removal of nutrient species
      from eutrophic water. The mutated water spinach was grown on floating beds, and
      growth chambers were used to examine the growth of three cultivars of water
      spinach with ion implantation for 14 days in simulated eutrophic water at both
      high and low nitrogen levels. The specific weight growth rates of three cultivars
      of water spinach with ion implantation were significantly higher than the
      control, and their NO(3)-N and NH(4)-N removal efficiencies were also greater
      than those of the control. Furthermore, compared with the control, the nitrogen
      contents in the plant biomass with ion implantation were higher as well.

PMID- 17524444
TI  - Nitrate stimulation of indigenous nitrate-reducing, sulfide-oxidising bacterial
      community in wastewater anaerobic biofilms.
AB  - The role of the nitrate-reducing, sulfide-oxidising bacteria (NR-SOB) in the
      nitrate-mediated inhibition of sulfide net production by anaerobic wastewater
      biofilms was analyzed in two experimental bioreactors, continuously fed with the
      primary effluent of a wastewater treatment plant, one used as control (BRC) and
      the other one supplemented with nitrate (BRN). This study integrated information
      from H(2)S and pH microelectrodes, RNA-based molecular techniques, and the time
      course of biofilm growth and bioreactors water phase. Biofilms were a net source
      of sulfide for the water phase (2.01 micromol S(2-)(tot)m(-2)s(-1)) in the
      absence of nitrate dosing. Nitrate addition effectively led to the cessation of
      sulfide release from biofilms despite which a low rate of net sulfate reduction
      activity (0.26 micromol S(2-)(tot)m(-2)s(-1)) persisted at a deep layer within
      the biofilm. Indigenous NR-SOB including Thiomicrospira denitrificans, Arcobacter
      sp., and Thiobacillus denitrificans were stimulated by nitrate addition resulting
      in the elimination of most sulfide from the biofilms. Active sulfate reducing
      bacteria (SRB) represented comparable fractions of total metabolically active
      bacteria in the libraries obtained from BRN and BRC. However, we detected changes
      in the taxonomic composition of the SRB community suggesting its adaptation to a
      higher level of NR-SOB activity in the presence of nitrate.

PMID- 17524445
TI  - Removal of antibiotics in conventional and advanced wastewater treatment:
      implications for environmental discharge and wastewater recycling.
AB  - Removal of 28 human and veterinary antibiotics was assessed in a conventional
      (activated sludge) and advanced (microfiltration/reverse osmosis) wastewater
      treatment plant (WWTP) in Brisbane, Australia. The dominant antibiotics detected
      in wastewater influents were cephalexin (med. 4.6 microg L(-1), freq. 100%),
      ciprofloxacin (med. 3.8 microg L(-1), freq. 100%), cefaclor (med. 0.5 microg L(
      1), freq. 100%), sulphamethoxazole (med. 0.36 microg L(-1), freq. 100%) and
      trimethoprim (med. 0.34 microg L(-1), freq. 100%). Results indicated that both
      treatment plants significantly reduced antibiotic concentrations with an average
      removal rate from the liquid phase of 92%. However, antibiotics were still
      detected in both effluents from the low-to-mid ng L(-1) range. Antibiotics
      detected in effluent from the activated sludge WWTP included ciprofloxacin (med.
      0.6 microg L(-1), freq. 100%), sulphamethoxazole (med. 0.27 microg L(-1), freq.
      100%) lincomycin (med. 0.05 microg L(-1), freq. 100%) and trimethoprim (med. 0.05
      microg L(-1), freq. 100%). Antibiotics identified in microfiltration/reverse
      osmosis product water included naladixic acid (med. 0.045 microg L(-1), freq.
      100%), enrofloxacin (med. 0.01 microg L(-1), freq. 100%), roxithromycin (med.
      0.01 microg L(-1), freq. 100%), norfloxacin (med. 0.005 microg L(-1), freq.
      100%), oleandomycin (med. 0.005 microg L(-1), freq. 100%), trimethoprim (med.
      0.005 microg L(-1), freq. 100%), tylosin (med. 0.001 microg L(-1), freq. 100%),
      and lincomycin (med. 0.001 microg L(-1), freq. 66%). Certain traditional
      parameters, including nitrate concentration, conductivity and turbidity of the
      effluent were assessed as predictors of total antibiotic concentration, however
      only conductivity demonstrated any correlation with total antibiotic
      concentration (p=0.018, r=0.7). There is currently a lack of information
      concerning the effects of these chemicals to critically assess potential risks
      for environmental discharge and water recycling.

PMID- 17524446
TI  - Characteristics of aggregates formed by electroflocculation of a colloidal
      suspension.
AB  - Electroflocculation (EF) is becoming recognized as an alternative process to
      conventional coagulation/flocculation, although both are somewhat different. The
      electrical current applied in EF to generate the active coagulant species creates
      a unique chemical/physical environment which affects coagulation mechanisms and
      subsequent aggregate formation. The chemical and physical characteristics of an
      electroflocculated kaolin suspension and the morphology/fractal dimension of the
      resulting aggregates were examined. An EF cell was operated in batch mode and
      comprised of two concentric electrodes--a stainless steel cathode (outer
      electrode) and an aluminum anode (inner electrode). The cell was run at constant
      current between 0.05 and 0.3A, velocity gradients were 0-30s(-1). The results
      show that the simultaneous hydrolysis occurring has a profound effect on the
      final pH and consequently on the coagulation mechanisms as indicated by
      differences in zeta potential measured. Moreover, the electrical field induced by
      passage of a current has an apparent effect on particle transport. A linear
      correlation between floc size and current was observed and lower fractal
      dimensions were obtained for larger floc sizes. The fractal dimensions of the
      flocs obtained in EF are on average lower than those reported for conventional
      coagulation.

PMID- 17524447
TI  - Using DNA suspension arrays to identify library-independent markers for bacterial
      source tracking.
AB  - We developed a suspension array to enhance the ability to use library-independent
      genetic markers for bacterial source tracking. Six markers from Enterococcus spp.
      were selected to distinguish between cattle, humans, and cervids. Multiplex PCR
      was used to amplify fecal markers and resulting products were biotinylated and
      fragmented by nick translation followed by hybridization to polystyrene beads.
      Six populations of beads were included simultaneously in each assay where beads
      were labeled with an oligonucleotide probe complementary to one of the six
      library-independent markers. Hybridized products were detected on the beads using
      a 2-laser flow cytometer in a 96-well format. Testing with previously
      characterized strains showed that the assay could achieve 100% diagnostic
      sensitivity and >95% diagnostic specificity. Results from water samples were
      congruent for conventional PCR. Serial dilutions of template DNA demonstrated
      that the bench top analytic sensitivity of the entire assay was equivalent to
      <1600 cells. Suspension arrays permit greater certainty of product identification
      and this format can be expanded to include many additional markers.

PMID- 17524448
TI  - The effects of temperature, pH, and ammonia concentration on the inactivation of
      Ascaris eggs in sewage sludge.
AB  - The reported inactivation of Ascaris eggs during alkaline sludge stabilization is
      highly variable. The objective of our research was to better understand the
      sources of this variability by quantifying the effects of temperature, pH, and
      ammonia concentration on the inactivation of indigenous Ascaris eggs in
      wastewater sludge. Primary sludge was supplemented with ammonia (0, 1000, and
      5000 mg/l NH(3)-N) and Ca(OH)(2) and incubated in sealed bottles across the range
      of temperatures (20, 30, 40, and 50 degrees C) and pH (7 and 12) that may be
      encountered during treatment. Changes in egg viability over time were fit to a
      two-parameter kinetic model (shoulder and first-order region); to compare
      treatment conditions, the time for 99% inactivation (t(99)) was also calculated.
      Each 10 degrees C increase in temperature caused a significant decrease in t(99)
      at every pH and ammonia concentration tested. At 50 degrees C, the effect of
      temperature was dominant, such that no effect of pH or ammonia was observed. At
      30 and 40 degrees C, raising the pH from 7 to 12 decreased t(99), but at 20
      degrees C no pH effect was seen over 80 d (very little inactivation occurred). At
      20, 30, and 40 degrees C, the addition of ammonia dramatically decreased t(99).
      The effect of pH could not be completely separated from that of ammonia, as the
      unamended sludge samples contained 100-200mg/l indigenous ammonia. Because
      temperature, pH, and ammonia all contributed to Ascaris egg inactivation, it is
      essential that these parameters are measured and accounted for when assessing the
      effectiveness of alkaline stabilization. Furthermore, inactivation by ammonia
      could be exploited to improve the effectiveness of alkaline sludge stabilization.

PMID- 17524449
TI  - Biodegradation of four phthalate esters in sludge.
AB  - This study investigated the effects of ultrasonic pretreatment and various
      treatments on the aerobic degradation of four phthalic acid esters (PAEs) such as
      diethyl phthalate (DEP), benzyl butyl phthalate (BBP), di-n-butyl phthalate (DBP)
      and di-(2-ethyl hexyl)phthalate (DEHP) in sludge. The effect on PAE degradation
      of treating sludge with a 20 min sonication period at a power level of 0.1 W ml(
      1) was evaluated. The degradation rates of the four PAEs were DBP>BBP>DEP>DEHP.
      Degradation rate constants (k(1)) and half-lives (t(1/2)) for the four PAEs (50
      mg kg(-1)) ranged from 0.182 to 0.379 day(-1) and 1.8 to 3.8 days, respectively.
      The optimal pH for PAE degradation in sludge was 7.0 at 30 degrees C. PAE
      degradation was enhanced by the addition of yeast extract, brij 30 or brij 35 and
      inhibited by the addition of hydrogen peroxide. Our results show that a
      combination of ultrasonic pretreatment and biodegradation can effectively remove
      PAE from sludge.

PMID- 17524450
TI  - Organic compounds temporal trends at some invertebrate species from the
      Balearics, Western Mediterranean.
AB  - Concentrations of persistent organic pollutants (POPs) such as hexachlorobenzene
      (HCB), dichlore diphenyl trichloretane (DDT), polychlorinated biphenyls (PCBs),
      and gamma-hexachlorocyclohexane (gamma-HCH or lindane) were determined in tissue
      of marine benthic invertebrates such as Mytilus galloprovincialis, Chamelea
      gallina, Venus verrucosa, Lithophaga lithophaga and Paracentrotus lividus.
      Species were selected due to their habitat, trophic level, feeding behaviour and
      their consumption. Invertebrate species were systematically sampled from December
      1996 to December 2005 from several sites along the Balearic Islands. The highest
      concentrations of PCBs (785ng/g lipid) were found in M. galloprovincialis while
      the lowest concentrations were found in the sea-urchin P. lividus (193ng/g
      lipid). Among the 7 PCB quantified congeners the higher values are mainly
      obtained for CB138 and CB153. All bivalves presented higher PCBs contents than
      the sea-urchin P. lividus are possibly linked with the bioaccumulation process of
      POPs throughout the food web and to differential detoxifying mechanisms. The
      concentration of SigmaDDT exceeds that of HCB and gamma-HCH at all species and
      sampling stations. DDT concentrations ranged from 0.4ng/g ww at the bivalve C.
      gallina in 2002, to values of 15.8ng/g ww at the bivalve L. lithophaga in 1998.
      The values obtained for the organic compounds (HCH, HCB, PCBs, DDT) depend upon
      the place and year of sampling and are compared to values found by other authors
      for the mussel M. galloprovincialis in other Mediterranean areas. gamma-HCH and
      HCB were found in lower concentrations than the other POPs.

PMID- 17524451
TI  - Decolorization of direct dyes by salt fractionated turnip proteins enhanced in
      the presence of hydrogen peroxide and redox mediators.
AB  - The present paper demonstrates the effect of salt fractionated turnip (Brassica
      rapa) proteins on the decolorization of direct dyes, used in textile industry, in
      the presence of various redox mediators. The rate and extent of decolorization of
      dyes was significantly enhanced by the presence of different types of redox
      mediators. Six out of 10 investigated compounds have shown their potential in
      enhancing the decolorization of direct dyes. The performance was evaluated at
      different concentrations of mediator and enzyme. The efficiency of each natural
      mediator depends on the type of dye treated. The decolorization of all tested
      direct dyes was maximum in the presence of 0.6mM redox mediator at pH 5.5 and 30
      degrees C. Complex mixtures of dyes were also maximally decolorized in the
      presence of 0.6mM redox mediator (1-hydroxybenzotriazole/violuric acid). In order
      to examine the operational stability of the enzyme preparation, the enzyme was
      exploited for the decolorization of mixtures of dyes for different times in a
      stirred batch process. There was no further change in decolorization of an
      individual dye or their mixtures after 60 min; the enzyme caused more than 80%
      decolorization of all dyes in the presence of 1-hydroxybenzotriazole/violuric
      acid. However, there was no desirable increase in dye decolorization of the
      mixtures on overnight stay. Total organic carbon analysis of treated dyes or
      their mixtures showed that these results were quite comparable to the loss of
      color from solutions. However, the treatment of such polluted water in the
      presence of redox mediators caused the formation of insoluble precipitate, which
      could be removed by the process of centrifugation. The results suggested that
      catalyzed oxidative coupling reactions might be important for natural
      transformation pathways for dyes and indicate their potential use as an efficient
      means for removal of dyes color from waters and wastewaters.

PMID- 17524452
TI  - Transformation of diclofenac by the indigenous microflora of river sediments and
      identification of a major intermediate.
AB  - Diclofenac is a non-steroidal anti-inflammatory drug, which tends to be
      relatively persistent in the environment. Now, a fixed-bed column bioreactor
      filled with sediment from the creek Munzbach (Freiberg/Saxony) under aerobic
      conditions showed rapid removal of diclofenac in a concentration range of 3-35
      microM without previous adaptation. The conversion of higher concentrations up to
      260 microM was accompanied by conspicuously decreased turnover rates indicating a
      toxic effect of this drug or its resulting metabolic burden on the indigenous
      microflora. A major metabolite occurred transiently and was identified by NMR and
      MS to be the p-benzoquinone imine of 5-hydroxydiclofenac. Abiotic adsorption to
      the biofilm was shown to determine the further fate of this reactive product of 5
      hydroxydiclofenac (aut-)oxidation. The apparent lack of a degradative potential
      for this compound as well as the failure to detect an enrichment of diclofenac
      depleting microbial activity both indicate a cometabolic nature of diclofenac
      transformation. 4'-Hydroxy-diclofenac, the favoured transformation product of
      eucaryotic diclofenac metabolism, could not be identified. The ability to convert
      diclofenac was shown to be widespread among biofilms from different river
      sediments, but measured rates obviously do not correlate with the total microbial
      activity. In addition, application of sediments from locations exposed to
      communal waste water effluents did not indicate any form of adaptation measured
      as an increased specific diclofenac depletion rate.

PMID- 17524453
TI  - Degradation of inhibitory substances by heterotrophic microorganisms during
      bioleaching of heavy metals from anaerobically digested sewage sludge.
AB  - The presence of organic acids was found to be inhibitory to the bioleaching of
      sewage sludge and the objective of the present study was to elucidate the roles
      of heterotrophic microorganisms in removing organic acids during the bioleaching
      of heavy metals from anaerobically digested sewage sludge. Microbiological
      analysis showed that acetic and propionic acids posed a severe inhibitory effect
      on iron-oxidizing bacteria as reflected by a sharp decrease in their viable
      counts in the first 4d and it only started to increase 2d after the depletion of
      both acids. Biodegradation of these inhibitory organic acids was revealed by
      sharp increases in total fungi and acidophiles between day 3 and day 5 which
      coincided with degradation of organic acids. This was further confirmed by the
      increases in total counts of both acetate and propionate degraders in the same
      period. Two yeast strains Y4 and Y5 with strong ability to degrade acetate and/or
      propionate were isolated and identified as Pichia sp. and Blastoschizomycetes
      capitatus, respectively. B. capitatus Y5 was an more important player in removing
      the inhibitory organic acids during the bioleaching process since it could
      utilize both acetate and propionate as sole carbon source while Pichia sp. Y4 was
      an strict acetate degrader. Results from the present study not only provided the
      evidence for biodegradation of organic acids by heterotrophs, but also disclosed
      a biological mechanism for the initiation of bioleaching of organic acid-laden
      sewage sludge.

PMID- 17524454
TI  - A municipal solid waste incinerator as the single dominant point source of
      PCDD/Fs in an area of increased non-Hodgkin's lymphoma incidence.
AB  - Since 1971, a municipal solid waste incinerator (MSWI) with high dioxin emission
      levels has been in operation in Besancon, France. We recently found a 2.3-fold
      risk of non-Hodgkin's lymphoma in the highest exposure zone using a Gaussian-type
      dispersion model as a proxy for dioxin exposure. However, the sources of PCDD/Fs
      in this area are a matter of controversy. The aim of this survey was therefore to
      examine the nature of the PCDD/F soil contamination in the surroundings of the
      MSWI to characterize whether more than one potential emission source could
      explain the presence of the PCDD/Fs. PCDD/F congener profiles were determined in
      75 soil samples collected in the vicinity of the MSWI. They were compared
      according to the most environmentally impacted zones and to various spatial
      contrasts. PCDD/F concentrations ranged from 0.25 to 28.06 pg WHO-TEQ g(-1). Two
      different clustering algorithms identified the same main cluster (consisting of
      73 samples). The remaining two soil samples composed either one, or two clusters.
      All clusters showed similar congener profiles. Moreover, no contrast was observed
      for congener distributions between complex and simple topographies, inside and
      outside the city boundary, the two most and the two least exposed areas,
      reflecting a common fingerprint. Congener profiles indicate that the area under
      influence of the MSWI is not subject to other point sources of PCDD/Fs. Since,
      the most polluting combustion chambers were recently shut down and replaced by a
      new one with up-to-date pollution control, slowly decreasing dioxin
      concentrations in the soils are to be expected.

PMID- 17524455
TI  - Comparative toxicity of imidacloprid, of its commercial liquid formulation and of
      diazinon to a non-target arthropod, the microcrustacean Daphnia magna.
AB  - Imidacloprid (IMI) is at the moment the insecticide with the world's fastest
      growing sales and is considered possible replacement for the widely used
      organophosphorus pesticide, diazinon, which is subject to phased revocation in
      many countries. In this study, biochemical, reproductive and survival parameters
      of the water flea (Daphnia magna) after chronic exposure to IMI, its commercial
      liquid formulation Confidor SL 200 and diazinon are presented and compared.
      According to the lowest observed effect concentrations, diazinon is more toxic to
      the reproduction of D. magna than IMI and Confidor SL 200, which exert similar
      toxicity. The same was observed for the survival, except that Confidor SL 200 is
      more toxic than IMI. In polluted aquatic environments, the actual levels of
      diazinon are potentially chronically hazardous to the reproduction of D. magna
      (risk quotient >1). According to very few measured environmental levels of IMI,
      the latter is not expected to be chronically hazardous, unless it is accidentally
      spilled in a small pond. In such case, the predicted concentrations of IMI would
      present a potential chronic risk to D. magna, and a potential acute risk to other
      aquatic invertebrates. In the future, higher environmental levels of IMI are
      expected due to its increasing use and physico-chemical properties. The
      literature survey summarized in this work suggests that further ecotoxicological
      studies with a broader spectrum of aquatic organisms are needed before IMI is
      classified as safer than currently applied pesticides.

PMID- 17524456
TI  - Thermodynamic behavior of rare metals in the melting process of municipal solid
      waste (MSW) incineration residues.
AB  - This study aims to identify the thermodynamic behavior of rare metal elements
      during the melting process of municipal solid waste incineration residues. The
      fate of several selected rare metal elements was investigated using two
      approaches: experimental and thermodynamic equilibrium calculation at two actual
      melting plants. The results revealed that Ag, Bi, Ga, Ge, In, Pd, Sb, Te, and Tl
      are readily volatilized as chloride and/or gaseous forms and then condensed in
      melting furnace fly ash. On the other hand, Cr, Ni, Ta, V, and Zr tend to mostly
      remain in molten slag. Sn is volatilized as SnS (g) under reducing conditions
      while volatilization is suppressed under oxidizing conditions. Thermodynamically,
      total volatilization of Mn as MnCl2 (g) occurred with highly available chlorine
      under oxidizing conditions. However, at the actual plants, only a small
      proportion was volatilized. As for Co, Mo, and W, no volatilization occurred at
      the actual plants although the calculations suggest that these elements can form
      volatile metal chloride and volatilize. Non-equilibrium and heterogeneity of the
      actual plant melting furnace could explain the discrepancy. This study provided a
      good qualitative view of the behavior of rare metals in the melting process, but
      further investigation is required to produce a more accurate simulation and to
      resolve the discrepancy.

PMID- 17524458
TI  - Laparoscopic extraperitoneal para-aortic lymphadenectomy.

PMID- 17524457
TI  - Molecular modeling and mutagenesis of gap junction channels.
AB  - Gap junction channels connect the cytoplasms of adjacent cells through the end-to
      end docking of hexameric hemichannels called connexons. Each connexon is formed
      by a ring of 24 alpha-helices that are staggered by 30 degrees with respect to
      those in the apposed connexon. Current evidence suggests that the two connexons
      are docked by interdigitated, anti-parallel beta strands across the extracellular
      gap. The second extracellular loop, E2, guides selectivity in docking between
      connexons formed by different isoforms. There is considerably more sequence
      variability of the N-terminal portion of E2, suggesting that this region dictates
      connexon coupling. Mutagenesis, biochemical, dye-transfer and
      electrophysiological data, combined with computational studies, have suggested
      possible assignments for the four transmembrane alpha-helices within each
      subunit. Most current models assign M3 as the major pore-lining helix. Mapping of
      human mutations onto a C(alpha) model suggested that native helix packing is
      important for the formation of fully functional channels. Nevertheless, a mutant
      in which the M4 helix has been replaced with polyalanine is functional,
      suggesting that M4 is located on the perimeter of the channel. In spite of this
      substantial progress in understanding the structural biology of gap junction
      channels, an experimentally determined structure at atomic resolution will be
      essential to confirm these concepts.

PMID- 17524460
TI  - The effects of cocaine preexposure on cocaine-induced taste aversion learning in
      Fischer and Lewis rat strains.
AB  - The Fischer (F344) and Lewis (LEW) inbred rat strains differ on a number of
      behaviors, including those induced by a variety of drugs of abuse. Although a
      number of physiological and biochemical differences between the strains have been
      reported following both single and repeated drug administration, studies
      assessing changes in the affective properties of drugs after repeated exposure
      are limited. To that end, using the F344 and LEW strains, the present study
      examined the effects of repeated exposure to cocaine on the subsequent
      acquisition of cocaine-induced conditioned taste aversions, a preparation often
      used in assessing the development of tolerance to the drug's aversive effects.
      Specifically, separate groups of male F344 and LEW rats received five injections
      of 32 mg/kg cocaine (or vehicle) prior to taste aversion conditioning with 32
      mg/kg cocaine (or vehicle). Vehicle-preexposed subjects of both strains acquired
      aversions to the cocaine-associated taste with no differences in the strength of
      the aversions. Further, cocaine-preexposed subjects displayed significantly
      attenuated aversions, an effect consistent with prior work with outbred animals.
      There was no difference between the two strains in this attenuation, suggesting
      that there were no genotype-specific differences in tolerance to cocaine's
      aversive effects. The data were discussed in relation to genetic/environmental
      interactions in the vulnerability to drugs of abuse.

PMID- 17524461
TI  - C57BL/6J mice show greater amphetamine-induced locomotor activation and dopamine
      efflux in the striatum than 129S2/SvHsd mice.
AB  - Inbred strains of mice have served as valuable models for studying genetic
      susceptibility to drug addiction, an alternative to genetically modified mouse
      models. This is the first study comparing amphetamine (AMPH) effects on locomotor
      stimulation and dopamine efflux between two inbred strains of mice C57BL/6J and
      129S2/SvHsd, frequently used as background strains for production of genetically
      engineered mice. There were no significant differences in basal locomotor
      activity and basal dopamine levels between the two strains. However, C57BL/6J
      mice showed greater AMPH-stimulated locomotor activity and AMPH-induced striatal
      dopamine efflux than 129S2/SvHsd mice. The differential AMPH effects could not be
      explained by differences in presynaptic dopamine components such as surface and
      total dopamine transporter (DAT) expression levels, striatal dopamine contents,
      and DAT activity. C57BL/6J and 129S2/SvHsd mice are excellent models for future
      identification of genetic, molecular, and behavioral components related to
      individual vulnerability to AMPH addiction. This study emphasizes the importance
      of mouse strain selections in the production of genetically modified mice for
      investigating phenotypes and mechanisms of psychostimulants.

PMID- 17524463
TI  - Legislative measures and tobacco control in Europe.

PMID- 17524462
TI  - Effects of buspirone on the immediate positive and delayed negative properties of
      intravenous cocaine as measured in the conditioned place preference test.
AB  - In prior work, we have demonstrated that the behavioral effects of cocaine adhere
      to the predictions of the opponent-process theory of drug action. Animals develop
      conditioned place preferences for distinct locations paired with the immediate
      effects of IV cocaine, but learn to avoid places paired with the effects present
      15-min post-injection. It was of interest to assess the putative role of 5-HT in
      producing the negative properties of cocaine since cocaine acts to inhibit the
      reuptake of serotonin (5-HT) and since such actions have been associated with
      anxiogenic consequences. Male rats were administered a reinforcing dose of
      cocaine (1.0 mg/kg IV) and then placed - either immediately or after a 15-min
      delay - into one side of a two-compartment (black-white) conditioned place
      preference (CPP) box for 5-min. On alternate days, the animals received IV saline
      injections and were placed in the opposite side of the CPP box. This continued
      for eight days after which animals had experienced 4 pairings of cocaine with one
      side (black or white) of the CPP apparatus, and 4 saline pairings with the
      opposite side. Other groups of rats were treated identically except that 30-min
      prior to placement into the apparatus, these animals received an IP injection of
      saline or buspirone (a partial 5-HT1A agonist) at a dose that we have shown to be
      anxiolytic (2.5 mg/kg IP). Control animals experienced either buspirone or saline
      pretreatments without cocaine. Our results confirm that animals increase the time
      spent on the side paired with the immediate effects of cocaine (compared to
      baseline), but tend to avoid the side paired with effects present 15-min post
      injection. Buspirone had no effect on the immediate rewarding properties of
      cocaine, but completely reversed the negative properties present 15-min post
      cocaine. These results are consistent with the view that attenuation of 5-HT
      neurotransmission (via the autoreceptor agonist properties of buspirone) can
      reverse the negative impact of IV cocaine.

PMID- 17524464
TI  - An mRNA m7G cap binding-like motif within human Ago2 represses translation.
AB  - microRNAs (miRNAs) bind to Argonaute (Ago) proteins and inhibit translation or
      promote degradation of mRNA targets. Human let-7 miRNA inhibits translation
      initiation of mRNA targets in an m(7)G cap-dependent manner and also appears to
      block protein production, but the molecular mechanism(s) involved is unknown and
      the role of Ago proteins in translational regulation remains elusive. Here we
      identify a motif (MC) within the Mid domain of Ago proteins, which bears
      significant similarity to the m(7)G cap-binding domain of eIF4E, an essential
      translation initiation factor. We identify conserved aromatic residues within the
      MC motif of human Ago2 that are required for binding to the m(7)G cap and for
      translational repression but do not affect the assembly of Ago2 with miRNA or its
      catalytic activity. We propose that Ago2 represses the initiation of mRNA
      translation by binding to the m(7)G cap of mRNA targets, thus likely precluding
      the recruitment of eIF4E.

PMID- 17524465
TI  - Identification of a female-pig profile associated with lower productivity on
      commercial farms.
AB  - At-risk female pigs were defined as females having characteristics of at least
      one of the four subgroups: females with reservices, lactation length (LL) 0-13
      days, weaning-to-first-mating interval (WMI) > or = 8 days, and abortion records.
      These females may have suboptimal reproductive performance. This study examined
      reproductive performance in at-risk females, and the relationships between at
      risk females, parity, season of mating, and the four subgroups. From 117 farms,
      102,494 parity records were categorized into at-risk females and non-at-risk
      females. Statistical mixed models were used to analyze reproductive performance.
      Of the 102,494 records, 19.6% were at-risk females. At-risk females had at least
      11.1% lower farrowing rates than non-at-risk females among all parities and
      seasons of mating (P<0.05). As parity increased from 1 to > or = 6, farrowing
      rate in at-risk females decreased from 74.1 to 62.9%, while the farrowing rate in
      non-at-risk females decreased from 87.3 to 82.0% (P<0.05). There was no
      difference in the number of pigs born alive between at-risk females and non-at
      risk females (P=0.810). Females at Parity 1 and those that mated during summer
      had the highest proportion of becoming at-risk females (P<0.001). Gilts and sows
      with abortion records had at least 39.3% lower farrowing rates than those with
      non-abortion records (P<0.001). Among the LL 0-13 days, the farrowing rate was
      below 70% regardless of WMI. Monitoring and reducing at-risk females is an
      opportunity for producers to improve herd productivity.

PMID- 17524466
TI  - Macroenvironment effects on oocytes and embryos in swine.
AB  - As in other domestic mammals, the interaction between genotype and environment in
      swine has profound effects on the ultimate phenotype of the individual born.
      Interactions within the litter in utero add an additional level of complexity in
      a litter-bearing species like the pig. Nutritional manipulations during the
      preovulatory period affect the maturity of the follicle and enclosed oocyte, and
      the metabolic and endocrine mechanisms potentially mediating these effects have
      been described. Extensive research on lactational catabolism in the first parity
      sow has established an association between the development of immature follicles
      and oocytes, and the reduced fertility of these sows when bred at the first
      postweaning estrus. This negative impact of lactational catabolism appears to be
      exaggerated in contemporary dam-lines by a minimal delay between weaning and
      first estrus, further limiting the maturity of the follicle and oocyte at the
      time of ovulation. Metabolic programming may induce gender-specific loss of
      embryos by Day 30 and affects embryonic development directly, without significant
      effects on placental size. In contrast, inadvertent crowding of embryos in utero,
      particularly evident in a sub-population of mature sows with high ovulation rates
      and moderate to high embryonic survival to Day 30, significantly limits placental
      development of crowded litters. However, even at Day 30, moderate crowding in
      utero also appears to affect myogenesis in the embryo in a gender-specific
      manner. In the absence of compensatory placental growth after Day 30, classic
      measures of IUGR are evident in surviving fetuses at Day 90 and at term.

PMID- 17524467
TI  - Changes in MPF and MAPK activities in porcine oocytes activated by different
      methods.
AB  - The effect of different oocyte activation methods on the dynamics of M-phase
      promoting factor (MPF) and mitogen-activated protein kinase (MAPK) activity in
      porcine oocytes were examined. Three activativation methods were tested: (1)
      electroporation (EP); (2) electroporation combined with butyrolactone I (BL), an
      inhibitor of cdc2 and cdk2 kinases; (3) electroporation followed by a treatment
      with cycloheximide (CHX), a protein synthesis blocker. The activity of cdc2 in
      MII oocytes was 0.067+/-0.011pmol/oocyte/min (mean+/-S.E.M.), which by 1h
      decreased in every treatment group (P<0.05) and stayed at low levels until 6h
      post-activation, approximately the time of pronuclear formation. The initial MAPK
      activity (0.123+/-0.017pmol/oocyte/min) also decreased 1h after each type of
      activation treatment (P<0.005). However, in the electroporation only group,
      activity reached its lowest level at 3h; thereafter, it started to recover and at
      later time points, MAPK activity did not differ from that in non-treated oocytes
      (P>0.1). In contrast, oocytes where electroporation was followed by protein
      kinase or protein synthesis inhibition had low MAPK activity by the time
      pronuclei were to be formed. Pronuclear formation in these groups (86.3+/-3.3%
      for EP+BL and 87.6+/-3.7% for EP+CHX) was higher compared to that found in the EP
      only oocytes (69.4+/-3.3%; P<0.05). These findings demonstrated that
      electroporation alone efficiently triggered the inactivation of MPF but not that
      of MAPK. In order to achieve low MAPK activity to allow high frequency of
      pronuclear formation, electroporation should be followed by a treatment that
      inhibits protein synthesis or specific protein kinases. The combined activation
      methods provided stimuli that efficiently induced both MPF and MAPK inactivation
      and triggered pronuclear formation with high frequencies.

PMID- 17524468
TI  - Strategies to improve fertility of high yielding dairy farms: Management of the
      dry period.
AB  - Reproductive performance of dairy cattle has been related to a wide variety of
      indicators of energy status, e.g., extent of negative energy balance, time of
      energy balance nadir, body weight loss, body condition score, and body condition
      score loss. Energy balance begins to decrease during the last few weeks prior to
      calving primarily due to a 30-35% reduction in feed intake. Cows typically remain
      in negative energy balance for five to seven weeks postpartum. Nutritional
      strategies to improve energy balance during the transition period include fat
      supplementation and feeding additional nonfiber carbohydrate. Unfortunately,
      neither approach is likely to markedly enhance energy status, although fat
      supplementation may increase reproductive efficiency independent of any effect on
      energy balance. Alternative management strategies may be required to improve
      fertility of dairy cows. Shortening or eliminating the dry period may improve
      energy status of dairy cows and increase reproductive efficiency. Shortening or
      eliminating the dry period may enhance dry matter intake during the transition
      period, decrease milk energy output, or both. A preliminary study using small
      animal numbers indicated that reducing dry period length to 28 or 0 days may
      decreases days to first ovulation, increase first service conception rate, and
      decrease days open. A follow-up study employing large animal numbers confirmed
      that reducing dry period length from 55 to 34 days can decrease days to first
      ovulation and decrease the percentage of anovular cows. The reduction in days
      open was greater for older cows than second parity cows. The reduction in days
      open was not related to effects of treatment on milk yield. Shortening or
      eliminating the dry period may be a more successful approach to improving
      reproductive efficiency than diet manipulation.

PMID- 17524469
TI  - Messenger RNA in oocytes and embryos in relation to embryo viability.
AB  - Messenger RNA (mRNA) expression techniques have become a powerful tool to analyze
      the relative abundance of transcripts related to oocyte and/or embryo quality.
      Numerous efforts to identify candidate genes for the developmental competence of
      bovine oocytes and embryos have been made employing different strategies. The
      preimplantation bovine embryo is initially under the control of maternal genomic
      information that is accumulated during oogenesis. Soon, the genetic program of
      development becomes dependent upon new transcripts derived from activation of the
      embryonic genome. The early steps in development including maturation,
      fertilization, timing of first cleavage, activation of the embryonic genome,
      compaction, and blastocyst formation can be affected by the culture media and
      conditions as well as the production procedure itself. These perturbations can
      possibly result in a dramatic decrease of the quality of the resulting
      blastocysts, and may even affect the viability of offspring born after transfer.

PMID- 17524470
TI  - Toward culture of single gametes: the development of microfluidic platforms for
      assisted reproduction.
AB  - During the last few decades in vitro production of mammalian embryos and assisted
      reproductive technologies such as embryo transfer, cryopreservation, and cloning
      have been used to produce and propagate genetically superior livestock. However,
      efficiencies of these technologies remain low. For these technologies to become
      more commercially viable, the efficiencies must improve. Despite this importance
      of reproduction for the livestock industry, little progress in decreasing
      embryonic mortality has been made. The livestock industry has succeeded in
      achieving large increases in average milk production of dairy cattle, growth rate
      in beef cattle and leanness in swine but reproductive efficiency has actually
      decreased. For example, research has provided little progress toward developing
      an objective method to examine viability of a single living embryo. At the same
      time, the growth of miniaturization technologies beyond integrated circuits and
      toward small mechanical systems has created opportunities for fresh examination
      of a wide range of existing problems. While the investigation and application of
      miniaturization technologies to medicine and biology is progressing rapidly,
      there has been limited exploration of microfabricated systems in the area of
      embryo production. Microfluidics is an emerging technology that allows a fresh
      examination of the way assisted reproduction is performed. Here we review the
      progress in demonstrating microfluidic systems for in vitro embryo production
      (IVP) and embryo manipulation. Microfluidic technology could have a dramatic
      impact on the development of new techniques as well as on our basic understanding
      of gamete and embryo physiology.

PMID- 17524471
TI  - Use of insulin-like growth factor-1 to improve post-transfer survival of bovine
      embryos produced in vitro.
AB  - Use of in vitro produced embryos in commercial settings is limited by alterations
      in embryo function that result in reduced embryo and fetal survival and increased
      fetal, placental and neonatal abnormalities. One potential strategy to improve
      the efficiency of in vitro embryo production systems is to modify embryo culture
      conditions to more closely mimic embryo physiology in vivo. The milieu of the
      reproductive tract contains various growth factors and regulatory molecules which
      can regulate embryonic development. One of these molecules, insulin-like growth
      factor-1 (IGF-1), has been reported to have beneficial effects on bovine embryo
      development in vitro. Addition of IGF-1 to embryo culture can increase pregnancy
      and calving rates in lactating dairy cows. However, recent research indicates
      that such an effect is only observed when recipients are heat-stressed. In non
      heat stressed animals, IGF-1 treatment does not affect conceptus length or
      interferon-tau secretion; thus, it is not likely that IGF-1 promotes embryo
      survival by blocking the luteolytic cascade. On the other hand, IGF-1 treatment
      can alter the relative abundance of certain developmentally important
      transcripts. Such differences may be important to improve embryo survival during
      heat stress. Further research into the effect of IGF-1 on gene expression and DNA
      methylation are warranted. Results indicate that modification of embryo culture
      with a growth factor can affect embryo survival after transfer. It is important
      that future research evaluating modifications to embryo culture also includes
      experiments involving transfer of embryos to recipients. Such experiments are
      important to demonstrate that proposed modifications actually improve post
      transfer embryonic survival.

PMID- 17524472
TI  - Determination of the properties of an experimental glass polyalkenoate cement
      prepared from niobium silicate powder containing fluoride.
AB  - OBJECTIVES: The purpose of this paper is to modify the conventional calcium
      fluoro-alumino-silicate glass, which is used in the formation of glass ionomer
      cements (CIGs) by the niobium addition and to study the properties of GICs
      obtained. MATERIALS AND METHODS: Sol-gel process was used to prepare the powder
      at lower temperature than fusion method. Glass-ceramic powder obtained in this
      way was used to prepare the GICs. The properties such as working and setting
      times, microhardness and diametral tensile strength were evaluated for the
      experimental GICs and a commercial luting cement. RESULTS: The ideal
      powder:liquid (P:L) ratio determined to prepare the experimental GICs was equal
      to 1:1. The cements prepared using this ratio showed working and setting times
      similar to the commercial GICs. In mechanical tests it was observed that
      microhardness and diametral tensile strength of the experimental GICs decreased
      significantly with the reduction of P:L ratio. On the other hand, the results
      obtained in microhardness tests indicated that the presence of niobium was a
      positive factor. SIGNIFICANCE: The chemical process allows the development of
      glass-ceramic powder at 600 degrees C which is the goal of the present paper. It
      was concluded that GICs containing niobium might be used in dental applications
      and these results encourage further researches on other compositions.

PMID- 17524473
TI  - Survival of Vibrio alginolyticus in seawater and retention of virulence of its
      starved cells.
AB  - The aim of this study was to evaluate the survival responses of four strains of
      Vibrio alginolyticus in seawater under starvation conditions. We used microcosms
      containing sterilised seawater and incubated at ambient temperature (22-25
      degrees C). V. alginolyticus maintained its culturability for at least nine
      months. Long-term-starved cells showed an absence or a decrease in their
      enzymatic activities. Resuscitation assays of viable but non-culturable (VBNC)
      cells were conducted and the recovery of these cells was achieved after the
      addition of nutrients. Amplified 16S ribosomal DNA (rDNA) restriction analysis
      (ARDRA) was used to confirm that the same strain of V. alginolyticus persisted in
      all microcosms during a long period of time. Starved cells maintained their
      infectivity for gilt head sea bream (Sparus aurata) and sea bass (Dicentrachus
      labrax) as determined by intraperitoneal challenges.

PMID- 17524474
TI  - Elucidation of the physicomechanical and ab initio quantum energy transitions of
      a crosslinked PLGA scaffold.
AB  - This study elucidated the in vitro physicomechanical transitions of a crosslinked
      polylactic-co-glycolic acid (PLGA) scaffold, utilizing quantum mechanics to
      compute the ab initio energy requirements of a salted-out and subsequently
      crosslinked PLGA scaffold interacting with simulated physiological fluid,
      phosphate buffered saline (PBS) (pH 7.4, 37 degrees C) at a molecular level.
      Twenty-six salted-out PLGA scaffolds were formulated using a four factor, two
      centerpoint quadratic Face-Centered Central Composite Design (FCCD). PLGA
      molecular mass, PLGA concentration, water volume and salting-out reaction time
      were the dependant formulation variables. Subsequent to PLGA solubilization in
      dimethyl formamide (DMF), protonated water was added to induce salting-out of
      PLGA into a scaffolds that were immersed in PBS, oscillated at 100 rpm, and
      analyzed at pre-determined time intervals for their physicomechanical and ab
      initio quantum energy transitions. Results indicated that the matrix resilience
      (MR) decreased with longer incubation periods (MR=35-45%) at day 30. Scaffolds
      salted-out using higher PLGA concentrations exhibited minimal changes in MR and
      the matrix ability to absorb energy was found to closely correlate with the
      scaffold residence time in PBS. Spartan-based ab initio quantum energy
      predictions elucidated the potential scaffold stability from a molecular
      viewpoint and its suitability for use in rate-modulated drug delivery.

PMID- 17524475
TI  - In vitro blood reactivity to hydroxylated and non-hydroxylated polymer surfaces.
AB  - Complement activation on hydroxyl-group-bearing surfaces is regarded as the main
      reason for granulocyte activation in applications of blood-contacting medical
      devices such as extracorporeal blood purification. However, the factors inducing
      the cell adhesion so far remained ambiguous. For a dedicated research, whole
      blood was incubated with a set of structurally similar polymer coatings on glass
      with either hydroxy or ether functionalities. By co-incubation of an activating
      with a non-activating surface, the reaction of granulocytes activated by
      complement fragments on non-activating surfaces could be evaluated. As expected,
      hydroxyl-terminated polymer layers induced much higher levels of complement
      activation than those with ether functionalities. Leukocyte activation, as
      measured by the expression of CD11b, correlated closely with the presence of free
      complement fragment C5a. However, adhesion of leukocytes was rather associated
      with the adsorption of activated fragments of C3 than with the activation level
      of the cells. Moreover, it was found that adsorbed quantities of fibrin and
      fibrinogen had little influence on leukocyte adhesion. It is concluded that the
      activation of leukocytes is triggered by soluble complement factors such as C5a
      while their adhesion on hydroxy-bearing surfaces is mainly triggered by the
      presence of surface-bound complement fragment C3b.

PMID- 17524476
TI  - Expression of cell adhesion receptors in human osteoblasts cultured on
      biofunctionalized poly-(epsilon-caprolactone) surfaces.
AB  - This study was aimed to investigate whether the activation of poly-(epsilon
      caprolactone) (PCL) surface by low-energy irradiation and/or the
      biofunctionalization by absorption of arginine-glycine-aspartic sequences (RGD),
      can modify the expression of integrins closely related to the osteoblast
      activity. For this purpose, we analysed the physicochemical changes induced by
      irradiation and RGD immobilization, the consequences on cell adhesion and
      spreading, and the effects on integrin expression. PCL irradiated with 5 x
      10(15)He(+)/cm(2) (10 keV energy) (irr-PCL) showed an altered surface layer with
      a partial loss of carboxyl species and the formation of carbonyl groups.
      Moreover, irr-PCL showed a small smoothening effect and a less polar character in
      comparison to the pristine ones. The RGD immobilization was observed only on irr
      PCL (surface coverage: 7.0 pmol/cm(2)). Human osteoblasts (hOB) were cultured on
      untreated PCL (ut-PCL), ut-PCL+RGD, irr-PCL, and irr-PCL+RGD. After 24h, ut-PCL
      hindered the cell adhesion, while a discrete layer of hOB with a good
      cytoskeleton organization was detected on irr-PCL and irr-PCL+RGD. Before
      seeding, the single hOB suspension expressed alpha1, alpha2, alpha3, alpha5,
      beta1, and alphaVbeta3; after 24h, cells cultured on tissue-plastic expressed
      high levels of beta1 and alphaVbeta3, while alpha1 showed a low intensity and
      alpha2, alpha3, and alpha5 were negative. beta1 and alphaVbeta3 were selected to
      evaluate the interaction between cells and PCL samples. The beta1 expression was
      higher in hOB cultured on irr-PCL than on the other samples. A significant
      increase in alphaVbeta3 expression was observed only in irr-PCL+RGD, and
      confirmed by the gene expression analysis. In conclusion, ion irradiation and RGD
      adsorption on PCL surfaces modulate the expression of integrin involved in hOB
      growth and function, indicating the effectiveness of biomimetic surfaces in
      promoting cell adhesion. Ultimately, the study of integrin expression may suggest
      proper changes to the surface structure in order to improve the osteoconductivity
      of selected materials.

PMID- 17524477
TI  - The extracellular matrix as a biologic scaffold material.
AB  - Biologic scaffolds composed of naturally occurring extracellular matrix (ECM)
      have received significant attention for their potential therapeutic applications.
      The full potential of the ability of ECM scaffolds to promote constructive
      remodeling will not be realized, however, until an understanding of the biology
      and the external influences that affect biology, are better achieved. The factors
      that appear important for the constructive remodeling of ECM biologic scaffolds
      are its ability to be rapidly and completely degraded with the generation of
      downstream bioactive molecules, the bioinductive properties of the functional
      molecules that compose native ECM material and the ability to engineer its
      mechanical properties at the time of implantation through an understanding of its
      collagen fiber microstructure.

PMID- 17524478
TI  - Synthesis and characterization of chemically condensed oligoethylenimine
      containing beta-aminopropionamide linkages for siRNA delivery.
AB  - Polyethylenimines (PEI) are often inefficient in gene knockdown experiments with
      small interfering RNA (siRNA), presumably due to the strong complexing
      properties. A more efficient and potentially degradable oligoethylenimine-based
      carrier was synthesized by the condensation of 800 molecular weight PEI oligomers
      with hexanedioldiacrylate. Reaction conditions were chosen such that Michael
      reaction occurs followed by complete N-acylation of all residual ester bonds
      resulting in beta-aminopropionamide linkage sites and an average molecular weight
      of 30,000. Based on NMR analysis, these conditions produced 38% tertiary amides
      and 62% secondary amides, with about 2% residual carboxylate, presumably from
      hydrolysis. The ionizable equivalent weight of the carrier increased to 51,
      compared to a value of 43 for standard PEI. Sensible in vitro knockdown of the
      luciferase gene in stably transfected HUH7 cells, up to 80% in comparison to non
      specific siRNA, demonstrated its suitability for siRNA delivery.

PMID- 17524479
TI  - In vitro, in vivo and post explantation testing of glucose-detecting biosensors:
      current methods and recommendations.
AB  - To date, there have been a number of cases where glucose sensors have performed
      well over long periods of implantation; however, it remains difficult to predict
      whether a given sensor will perform reliably, will exhibit gradual degradation of
      performance, or will fail outright soon after implantation. Typically, the
      literature emphasizes the sensor that performed well, while only briefly (if at
      all) mentioning the failed devices. This leaves open the question of whether
      current sensor designs are adequate for the hostile in vivo environment, and
      whether these sensors have been assessed by the proper regimen of testing
      protocols. This paper reviews the current in vitro and in vivo testing procedures
      used to evaluate the functionality and biocompatibility of implantable glucose
      sensors. An overview of the standards and regulatory bodies that govern
      biomaterials and end product device testing precedes a discussion of up-to-date
      invasive and non-invasive technologies for diabetes management. Analysis of
      current in vitro, in vivo, and then post explantation testing is presented. Given
      the underlying assumption that the success of the sensor in vitro foreshadows the
      long-term reliability of the sensor in the human body, the relative merits of
      these testing methods are evaluated with respect to how representative they are
      of human models.

PMID- 17524480
TI  - Breast cancer resistance protein (Bcrp1/Abcg2) in mouse placenta and yolk sac:
      ontogeny and its regulation by progesterone.
AB  - Breast Cancer Resistance Protein (BCRP), a recently-discovered transporter
      belonging to ABC superfamily, is highly expressed within the labyrinth of the
      placenta, the primary site of exchange between the maternal and fetal
      circulation. It has been proposed to function as an efflux pump protecting the
      fetus from a wide range of xenobiotics. It has also been recently shown that the
      yolk sac, in addition to the placenta, may be involved in transport of certain
      substances to and from the fetus. We hypothesised that there are changes in
      placental Bcrp1 (the mouse orthologue of human BCRP) expression during pregnancy
      and that these correlate with changes in progesterone production that occur in
      late gestation. We also hypothesised that Bcrp1 is expressed in the yolk sac, and
      that levels change with advancing gestation. Either whole concepti, or placenta
      and yolk sac, were collected from pregnant mice and analysed at embryonic (E) day
      9.5, 12.5, 15.5 and 18.5 (term approximately E19.5). Peak expression of Bcrp1
      mRNA was detected using in situ hybridisation within the placenta at E9.5 and the
      yolk sac at E12.5. There was a significant decrease thereafter in both tissues
      (p<0.001). In contrast, expression of Bcrp1 protein as assessed by
      immunohistochemistry and Western immunoblots did not change significantly during
      gestation either in the placenta nor the yolk sac, and no sex difference in Bcrp1
      protein expression in either tissue was observed at E12.5. Daily progesterone
      treatment starting at E14.5 and continuing until E18.5 significantly increased
      maternal progesterone levels, but did not elicit any changes in the Bcrp1 mRNA or
      Bcrp1 protein expression either in the placenta or the yolk sac. Significant
      expression of Bcrp1 protein in fetal tissue was evident at the end of gestation,
      while expression in the fetal brain endothelium was evident as early as E12.5. We
      suggest that the placenta and the yolk sac, both of which express Bcrp1, may
      limit fetal exposure to the potentially adverse effects of xenobiotics including
      therapeutic drugs which the mother may be exposed to during pregnancy. The
      significant decrease in Bcrp1 mRNA expression in both the yolk sac and the
      placenta from mid to late gestation may be counter-balanced by an increase in
      Bcrp1 expression in fetal organs involved in absorption, excretion and
      protection.

PMID- 17524481
TI  - Antiphase oscillations of endothelium and smooth muscle [Ca2+]i in vasomotion of
      rat mesenteric small arteries.
AB  - The mechanisms leading to vasomotion in the presence of noradrenaline and
      inhibitors of the sarcoplasmic/endoplasmic reticulum calcium ATPase were
      investigated in isolated rat mesenteric small arteries. Isobaric diameter and
      isometric force were measured together with membrane potential in endothelial
      cells and smooth muscle cells (SMC). Calcium in the endothelial cells and SMC was
      imaged with confocal microscopy. In the presence of noradrenaline and
      cyclopiazonic acid, ryanodine-insensitive oscillations in tone were produced. The
      frequency was about 1 min(-1) and amplitude about 70% of the maximal tone. The
      amplitude was reduced by indomethacin and increased with L-NAME. Vasomotion was
      inhibited by nifedipine and by 40 mM potassium. The frequency was increased and
      amplitude decreased by removal of the endothelium and by application of
      charybdotoxin and apamin. The vasomotion was associated with in-phase
      oscillations of membrane potential in endothelial cells and SMC and oscillations
      of [Ca2+]i that were in near anti-phase. We suggest a working model for the
      generation of oscillation based on a membrane oscillator where ion channels in
      both endothelial cells and SMC interact via a current running between the two
      cell types through myoendothelial gap junctions, which sets up a near anti-phase
      oscillation of [Ca2+]i in the two cell types.

PMID- 17524482
TI  - Collagen-mediated survival signaling is modulated by CD45 in Jurkat T cells.
AB  - T cell activation is a critical step in the development of a proper immune
      response to infection and inflammation. This dynamic process requires efficient T
      cell receptor signaling, which in turn is modulated by integrin receptor
      activation and the actin cytoskeleton. CD45 is a key player in T cell receptor
      mediated signal transduction. However, its exact role in integrin mediated
      signaling in T cells remains to be elucidated. The present study addresses the
      relationship between CD45 and beta1-integrin mediated survival signaling in the
      human T leukemic cell line Jurkat, in which collagen receptors alpha1 beta1 and
      alpha2 beta1 integrins are localized. Wild type (WT)-Jurkat T cells treated with
      collagen demonstrated increased cell proliferation and survival. Monitoring the
      intracellular signaling pathways activated by collagen in WT-Jurkat cells
      revealed increased focal adhesion kinase (FAK) and extracellular signal-regulated
      kinase (ERK) activation. Moreover, examination of the actin cytoskeleton of WT
      Jurkat T cells treated with collagen demonstrated the presence of an organized
      cortical actin structure, reminiscent of the survival phenotype. This is in
      contrast to CD45-deficient J45.01 T cells, where collagen treatment failed to
      enhance cell proliferation/survival and was unable to stimulate FAK and ERK
      activity. In addition, the actin cytoskeleton of collagen treated J45.01 T cells
      was disorganized with cortical actin aggregates present throughout. The
      importance of an organized actin cytoskeleton to proper cell signaling and
      survival was further demonstrated by the inability of collagen treated WT-Jurkat
      cells to activate the FAK and ERK survival pathway in the presence of
      cytochalasin D, a cytoskeleton-disrupting drug. Consistently, addition of the
      CD45 specific inhibitor abolished collagen-stimulated FAK and ERK activation in
      WT-Jurkat cells, further depicting CD45 as the key mediator. Furthermore,
      collagen-mediated T cell signaling alone was able to activate IL-2 gene
      transcription devoid of concomitant T cell receptor activation. Taken together,
      these results are the first to demonstrate that CD45 is important in promoting
      cell survival by modulating integrin-mediated FAK/ERK signaling in Jurkat T cells
      and is involved in a distinct signal transduction pathway, separate from T cell
      receptor signaling, influencing T cell immune responses. Hence, this study will
      help further our knowledge about beta1-integrin mediated signaling in T cells,
      which may prove to be essential for the regulation of various T cell mediated
      immune responses.

PMID- 17524483
TI  - Mn(II)-monosubstituted polyoxometalates as candidates for contrast agents in
      magnetic resonance imaging.
AB  - Two mono-substituted manganese polyoxometalates, K(6)MnSiW(11)O(39) (MnSiW(11))
      and K(8)MnP(2)W(17)O(61) (MnP(2)W(17)), have been evaluated by in vivo and in
      vitro experiments as the candidates of potential tissue-specific contrast agents
      for magnetic resonance imaging (MRI). T1-relaxivities of 12.1mM(-1)s(-1) for
      MnSiW(11) and 4.7 mM(-1)s(-1) for MnP(2)W(17) (400 MHz, 25 degrees C) were higher
      than or similar to that of the commercial MRI contrast agent (GdDTPA). Their
      relaxivities in BSA and hTf solutions were also reported. After administration of
      MnSiW(11) and MnP(2)W(17) to Wistar rats, MR imaging showed longer and remarkable
      enhancement in rat liver and favorable renal excretion capability. The signal
      intensity increased by 74.0+/-4.9% for the liver during the whole imaging period
      (90 min) and by 67.2+/-5.3% for kidney within 20-70 min after injection at 40+/-3
      micromol kg(-1) dose for MnSiW(11). MnP(2)W(17) induced 71.5+/-15.1% enhancement
      for the liver in 10-45 min range and 73.1+/-3.2% enhancement for kidney within 5
      40 min after injection at 39+/-3 micromol kg(-1) dose. In vitro and in vivo study
      showed MnSiW(11) and MnP(2)W(17) being favorable candidates as the tissue
      specific contrast agents for MRI.

PMID- 17524484
TI  - The activation of platinum(II) antiproliferative drugs in carbonate medium
      evaluated by means of a DNA-biosensor.
AB  - We report on the binding of cisplatin, carboplatin and oxaliplatin to double
      stranded DNA in two different (phosphate and carbonate) buffers, using an
      electrochemical DNA-biosensor. The propensity of the electrophilic agent produced
      by hydrolysis to interact with DNA was measured as a function of the decrease of
      guanine oxidation signal of the metal-DNA adduct immobilized on a screen-printed
      electrode, by using square wave voltammetry. The results obtained confirm that
      carbonate reacts with platinum drugs to form activated carbonato complexes, which
      are able to react readily with DNA.

PMID- 17524485
TI  - Curcumin and cyclopalladated complexes: a recipe for bifunctional biomaterials.
AB  - The first examples of binuclear and mononuclear ortho-palladated complexes based
      on a functionalized 2-phenylquinoline ligand have been synthesized and fully
      characterized. Conjugating cyclopalladated fragments to curcumin family
      biologically active beta-diketones gives in one single molecule two different
      functionalities. The structural variations based on the curcuminoid structure
      have been tested for their in vitro cytotoxic activity. The activity of complexes
      comprised of a cyclopalladated fragment conjugated to functionalized bioactive
      ligands, represents the potential of organometallic systems in generating new
      bifunctional biomaterials.

PMID- 17524486
TI  - Bacteraemic pneumococcal pneumonia: impact of HIV on clinical presentation and
      outcome.
AB  - OBJECTIVES: The objectives of this study were to investigate the clinical and
      laboratory features, hospital course and outcome of patients with bacteraemic
      pneumococcal pneumonia, comparing HIV with non-HIV patients, as well as HIV
      patients from different parts of the world. METHODS: This was a multicentre
      prospective observational study of consecutive adult cases with bacteraemic
      pneumococcal pneumonia in 10 countries on 6 continents. RESULTS: A total of 768
      cases were recruited, of which 200 were HIV-infected; 166 were from South Africa.
      Lower age, i.v. drug use, fewer co-morbid illnesses, and a higher frequency of
      respiratory symptoms were significantly more likely to occur in HIV patients. The
      14-day mortality for the group as a whole was 14.5%, being 16% in the HIV
      patients and 13.9% in the non-HIV patients (not significant). When adjustments
      were made for age and severity of illness, HIV patients had significantly higher
      14-day mortality with significant trend for increasing 14-day mortality in those
      with lower CD4 counts. Despite differences in various clinical and laboratory
      parameters in patients from different parts of the world, on multivariate
      analysis, when adjusting for regional differences, the HIV-infected patients were
      still noted to have poorer 14-day mortality. CONCLUSIONS: This study, in contrast
      to previous investigations, indicates that there are significant differences in
      the clinical presentation and outcome of bacteraemic pneumococcal pneumonia when
      comparing HIV and non-HIV patients.

PMID- 17524488
TI  - The stress system in depression and neurodegeneration: focus on the human
      hypothalamus.
AB  - The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA)
      system. Activity of the corticotropin-releasing hormone (CRH) neurons in the
      hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the
      HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH) release from the
      pituitary, which subsequently causes cortisol release from the adrenal cortex.
      The CRH neurons co-express vasopressin (AVP) which potentiates the CRH effects.
      CRH neurons project not only to the median eminence but also into brain areas
      where they, e.g., regulate the adrenal innervation of the autonomic system and
      affect mood. The hypothalamo-neurohypophysial system is also involved in stress
      response. It releases AVP from the PVN and the supraoptic nucleus (SON) and
      oxytocin (OXT) from the PVN via the neurohypophysis into the bloodstream. The
      suprachiasmatic nucleus (SCN), the hypothalamic clock, is responsible for the
      rhythmic changes of the stress system. Both centrally released CRH and increased
      levels of cortisol contribute to the signs and symptoms of depression. Symptoms
      of depression can be induced in experimental animals by intracerebroventricular
      injection of CRH. Depression is also a frequent side effect of glucocorticoid
      treatment and of the symptoms of Cushing's syndrome. The AVP neurons in the
      hypothalamic PVN and SON are also activated in depression, which contributes to
      the increased release of ACTH from the pituitary. Increased levels of circulating
      AVP are also associated with the risk for suicide. The prevalence, incidence and
      morbidity risk for depression are higher in females than in males and
      fluctuations in sex hormone levels are considered to be involved in the etiology.
      About 40% of the activated CRH neurons in mood disorders co-express nuclear
      estrogen receptor (ER)-alpha in the PVN, while estrogen-responsive elements have
      been found in the CRH gene promoter region, and estrogens stimulate CRH
      production. An androgen-responsive element in the CRH gene promoter region
      initiates a suppressing effect on CRH expression. The decreased activity of the
      SCN is the basis for the disturbances of circadian and circannual fluctuations in
      mood, sleep and hormonal rhythms found in depression. Neuronal loss was also
      reported in the hippocampus of stressed or corticosteroid-treated rodents and
      primates. Because of the inhibitory control of the hippocampus on the HPA-axis,
      damage to this structure was expected to disinhibit the HPA-axis, and to cause a
      positive feedforward cascade of increasing glucocorticoid levels over time. This
      'glucocorticoid cascade hypothesis' of stress and hippocampal damage was proposed
      to be causally involved in age-related accumulation of hippocampal damage in
      disorders like Alzheimer's disease and depression. However, in postmortem studies
      we could not find the presumed hippocampal damage of steroid overexposure in
      either depressed patients or in patients treated with synthetic steroids.

PMID- 17524489
TI  - Glucocorticoid receptor transgenic mice as models for depression.
AB  - In the era of mutant mice generated as molecular in vivo models for complex
      pathogenetic and therapeutic aspects of particular human diseases, glucocorticoid
      receptor transgenic mice represent an interesting and promising tool. Animals
      carrying mutations of this receptor show alterations in the hypothalamic
      pituitary-adrenal (HPA)-system, which are comparable to those observed in
      depressed patients. Furthermore, similarities that may model the human disease
      have been described on the behavioral and pharmacological level, which increase
      the impact of such mutants. In this review we summarize different approaches used
      to alter or eliminate glucocorticoid receptor expression and function, and
      discuss their relevance as models for depression.

PMID- 17524487
TI  - Mechanisms of neurosteroid interactions with GABA(A) receptors.
AB  - Neuroactive steroids have some of their most potent actions by augmenting the
      function of GABA(A) receptors. Endogenous steroid actions on GABA(A) receptors
      may underlie important effects on mood and behavior. Exogenous neuroactive
      steroids have potential as anesthetics, anticonvulsants, and neuroprotectants. We
      have taken multiple approaches to understand more completely the interaction of
      neuroactive steroids with GABA(A) receptors. We have developed many novel steroid
      analogues in this effort. Recent work has resulted in synthesis of new enantiomer
      analogue pairs, novel ligands that probe various properties of the steroid
      pharmacophore, fluorescent neuroactive steroid analogues, and photoaffinity
      labels. Using these tools, combined with receptor binding and
      electrophysiological assays, we have begun to untangle the complexity of steroid
      actions at this important class of ligand-gated ion channel.

PMID- 17524490
TI  - Steroid-dependent plasticity of vocal motor systems: novel insights from teleost
      fish.
AB  - Vocal communication is a trait shared by most vertebrates. Non-mammalian model
      systems have provided exquisite examples of how motor and sensory systems,
      respectively, produce and encode the physical attributes of acoustic
      communication signals that play essential roles in mediating the dynamics of
      social behavior. These same models, mainly developed for a few species of fish,
      amphibians and birds, have proven to be equally important for demonstrating how
      steroids and other hormones shape the neural mechanisms of vocal communication.
      This review mainly considers recent studies in teleost fish demonstrating the
      role of steroids in the rapid modulation of the firing properties of a central
      pattern generator for vocalization. Thus, steroids, like other classes of
      neurochemicals, can play an instrumental role in reshaping the neurophysiological
      coding of motor patterning, in this case for social signaling behavior.

PMID- 17524491
TI  - Fast and easy colorimetric tests for single mismatch recognition by PNA-DNA
      duplexes with the diethylthiadicarbocyanine dye and succinyl-beta-cyclodextrin.
AB  - The 3,3'-diethylthiacarbocyanine (DiSC(2)(5)) dye is able to aggregate on full
      matched PNA-DNA duplexes by changing its absorption properties, which are
      manifested by an instantaneous colour shift from blue to purple. However the
      spontaneous aggregation of the dye also on mismatched duplexes and even on free
      PNA strands makes the test quite aspecific. Here it is demonstrated that the
      addition of succinyl-beta-cyclodextrin (Succ-beta-CyD) to the solutions
      containing PNA-DNA duplexes and the dye strongly enhances the specificity of the
      colour shift, allowing for a fast, very specific and extremely sensitive visual
      recognition of mismatches in DNA strands by using PNA probes in combination with
      the DiSC(2)(5) dye. The phenomenon has been studied by CD and NMR spectroscopies.
      The method has been optimized and preliminarily applied for the recognition of an
      apoE gene mutation in human DNA samples.

PMID- 17524492
TI  - Functional and immunochemical characterisation of different antibodies against
      the erythropoietin receptor.
AB  - Since it was discovered that the hematopoietic hormone erythropoetin (EPO) exerts
      neuroprotective effects in the CNS, many studies on the EPO receptor (EPOR)
      function and localisation in the CNS have been performed. For this purpose,
      commercially available anti-EPOR antibodies have often been applied. As the
      literature data on these antibodies show inconsistencies, we here systematically
      compared six frequently used, commercially available EPOR antibodies for
      different applications. Five of the antibodies appeared to specifically recognize
      recombinant rat and human EPOR in HEK293 cells by Western blotting, but the same
      antibodies yielded different and inconsistent results when human UT-7 cells or
      rat brain tissue were applied. Immunocytochemical staining of EPOR-transfected
      HEK cells only produced consistent results with three of the six antibodies. All
      antibodies stained neurons in rat brain sections, but with large differences in
      the staining pattern and only the C-20 EPOR antibody was found to label
      astrocytes. Since EPOR antibodies have been applied in several studies as EPOR
      antagonists, we further tested the antibodies for their capacity to functionally
      block the EPO-EPOR interaction in a cellular signalling system with STAT-5
      phosphorylation as readout. Here, only the MAB307 antibody showed a partial
      effect at concentrations of 5-50 microg/ml.

PMID- 17524493
TI  - Neuropsychological performance predicts clinical recovery in bipolar patients.
AB  - BACKGROUND: Although a number of investigations have reported cognitive deficits
      in patients with bipolar disorder, relatively few have focused on the
      relationship between these impairments and clinical outcome. METHODS: In order to
      help clarify the pattern of and extent to which cognitive deficits are present at
      the onset of illness and their relationship to outcome, we examined 26 bipolar
      patients during their first hospitalization and 20 psychiatrically healthy
      control subjects. All subjects completed tests of frontal/executive control,
      psychomotor speed and memory function at baseline and self-reports of clinical
      recovery (time to recover in days) at 12 months post study enrollment. RESULTS:
      At baseline, first episode bipolar patients demonstrated greater deficits
      relative to control subjects on neurocognitive measures, and a significant
      association was detected between time to recover and performance on a measure of
      frontal/executive function (interference condition of the Stroop; p=.05; derived
      interference: p=.04). A trend towards significance was also demonstrated between
      time to clinical recovery and verbal fluency (p=.06). CONCLUSIONS: These findings
      indicate that neuropsychological deficits are seen early in the course of bipolar
      disorder, prior to the effects of multiple or prolonged episodes, and may be
      associated with clinical outcome. Future studies are needed to determine whether
      changes in inhibitory processing or other cognitive function predict clinical
      outcome or are associated with treatment response.

PMID- 17524494
TI  - Work and family roles and the association with depressive and anxiety disorders:
      differences between men and women.
AB  - BACKGROUND: This study examined the associations of (combinations of) social
      roles (employee, partner and parent) with the prevalence of anxiety and
      depressive disorders and whether social roles contribute to the explanation of
      the female preponderance in these disorders. METHOD: This was a cross-sectional
      study using data from 3857 respondents aged 25-55 of NEMESIS (Netherlands Mental
      Health Survey and Incidence Study). Depression and anxiety disorders were
      measured using the CIDI 1.1. RESULTS: The OR of depressive disorders and anxiety
      disorders among women compared to men was 1.71 (95% CI: 1.40-2.10). Among both
      genders, the partner role was associated with decreased risks of depression and
      anxiety and the parent role was not. The work role was a significant protective
      factor of depression and anxiety for men (OR=0.40; 95% CI: 0.24-0.69) but not for
      women (OR=0.86; 95% CI: 0.66-1.12). The effect of the work role was positive
      among women without children (OR=0.28; 95% CI: 0.14-0.54), but not among those
      with children (OR=1.01; 95% CI: 0.75-1.35). The gender risk for depression and
      anxiety decreased significantly by adding the work role variables into the model.
      LIMITATIONS: This was a cross-sectional study. This study did not give insight
      into the quality of social roles. CONCLUSION: The work role contributed to the
      explanation of the female preponderance in depression and anxiety disorders.
      Considering depression and anxiety among women, a focus upon quality and meaning
      of the work role, and barriers in combining the work role and parent role may be
      essential.

PMID- 17524495
TI  - Vaccination of cattle with Danish and Pasteur strains of Mycobacterium bovis BCG
      induce different levels of IFNgamma post-vaccination, but induce similar levels
      of protection against bovine tuberculosis.
AB  - A number of studies have demonstrated significant protection of cattle against
      bovine tuberculosis following vaccination with the Pasteur strain of
      Mycobacterium bovis bacille Calmete-Guerin (BCG). However, it is unclear if other
      daughter strains of BCG are as effective, which is an important issue to resolve
      for a variety of regulatory compliance issues. This study compared the protective
      immune responses to bovine tuberculosis induced in cattle vaccinated with BCG
      Danish with those induced by BCG Pasteur. Groups of calves (n=10) were vaccinated
      with 10(6) colony forming units (CFU) BCG Pasteur prepared from a fresh liquid
      culture, 10(6) CFU BCG Danish prepared from a fresh liquid culture or 0.4 mg of
      reconstituted freeze-dried culture of BCG Danish. Another group (n=10) served as
      non-vaccinated controls. BCG Pasteur induced significantly higher and more
      sustained levels of bovine purified protein derivative (PPD)-specific gamma
      interferon (IFN-gamma) in whole-blood cultures following vaccination compared to
      either fresh culture BCG Danish or freeze-dried BCG Danish. Vaccination with a
      fresh culture of BCG Pasteur, fresh culture BCG Danish and freeze-dried BCG
      Danish gave a significant enhancement in three, four and three pathological and
      microbiological parameters of protection, respectively, compared to the non
      vaccinated group. These results demonstrate the Danish strain of BCG is a viable
      alternative to BCG Pasteur for vaccination of cattle as both strains had similar
      efficacy and there was little difference between freshly cultured and freeze
      dried formulation of BCG Danish. The results also show that post-vaccination
      antigen-specific IFN-gamma levels in whole blood is not always a reliable
      indicator of protection against a subsequent virulent challenge.

PMID- 17524496
TI  - Expression profiling of select cytokines in canine osteoarthritis tissues.
AB  - The objective of this study was to investigate the level of expression of five
      cytokines in four different articular tissues from the joints of dogs with and
      without osteoarthritis (OA). Articular tissues were harvested from the stifle
      (fat, cranial cruciate ligament, synovial membrane) or hip (articular cartilage)
      from eight dogs with OA secondary to cranial cruciate ligament disease (stifle)
      or hip dysplasia (hip), undergoing routine surgical treatment for the condition,
      and from five dogs euthanatized without orthopaedic disease. The mRNA transcript
      numbers for interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL
      8), interleukin-10 (IL-10) and interleukin-17 (IL-17) were determined by
      quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR).
      Increased expression of IL-1beta, IL-6 and IL-10 in OA synovial membrane,
      increased expression of IL-1beta and IL-6 in ruptured (OA) ligament, and reduced
      expression of IL-8 in OA synovial membrane were identified. Cytokine expression
      was detected in multiple tissues within the articular joint, but differential
      expression in OA was detected primarily in the synovial membrane and cranial
      cruciate ligament.

PMID- 17524497
TI  - Increased expression and localization of cyclooxygenase-2 in astrocytes of
      scrapie-infected mice.
AB  - A number of aspects of the pathogenesis of scrapie, the archetype disease of the
      transmissible spongiform encephalopathies (prion disorders), remain to be
      elucidated. There is increasing evidence that there are cerebral based
      inflammatory processes that may contribute to the pathogenesis and to the
      progression of a number of neurodegenerative disorders, including prion diseases.
      In peripheral tissues, a key element that controls the generation of
      proinflammatory mediators is the highly inducible protein cyclooxygenase-2 (COX
      2). In this study, in order to examine the possible association of COX-2 with the
      pathogenesis of scrapie, we analyzed the expression level and the cellular
      localization of COX-2 in the brains of control and scrapie-infected mice. The COX
      2 mRNA and protein levels were increased significantly compared to the control
      group of mice. By immunohistological analysis, intense immunoreactivity of COX-2
      was localized primarily in reactive astrocytes, with virtually no staining in
      sections from control mice. The staining for COX-2 was co-localized with the
      pathological form of the prion protein (PrP(Sc)) and with nuclear factor-kappa B
      (NF-kappaB). These results suggest that the upregulation of COX-2 expression in
      astrocytes may be related to the accumulation of PrP(Sc), and that COX-2 may then
      lead to the progression of scrapie, possibly by propagation of a cerebral
      inflammatory response.

PMID- 17524498
TI  - CTLA4 gene polymorphisms and multiple sclerosis in Northern Ireland.
AB  - Four CTLA4 polymorphisms were investigated in a Northern Irish collection of
      relapsing-remitting (RR) and primary-progressive (PP) multiple sclerosis (MS)
      patients. The CTLA4 promoter (-318 C/T), exon 1 (+49 A/G) and intergenic CT60
      SNPs, as well as a microsatellite found in the 3' UTR (AT(n)) were analysed in
      246 RRMS, 84 PPMS and 158 healthy controls. The A allele of the exon 1 +49 A/G
      SNP (OR=1.36; 95% CI=1.11-1.81; P=0.038), and more so the AA genotype (OR=1.70;
      95% CI=1.11-2.60; P=0.015) were associated with RR, but not PPMS. In the PPMS
      population, overall allele distribution of the AT(n) microsatellite was
      significantly different from that in the healthy controls. We did not find any
      association with the promoter (-318 C/T) or intergenic CT60 SNPs in either of the
      disease cohorts. In concordance with several recent studies, we detected a trend
      toward higher carriage rates of the +49 G allele in PP vs RR MS patients (66.7%
      vs 58.9%), though this was not significant. Our data highlight the CTLA4 +49 A/G
      and 3'UTR polymorphisms as potential modifiers of disease course in MS.

PMID- 17524499
TI  - The effect of the inter-phase delay interval in the spontaneous object
      recognition test for pigs.
AB  - In the neuroscience community interest for using the pig is growing. Several
      disease models have been developed creating a need for validation of behavioural
      paradigms in these animals. Here, we report the effect of different inter-phase
      delay intervals on the performance of Gottingen minipigs in the spontaneous
      object recognition test. The test consisted of a sample and a test phase. First,
      the pigs explored two similar objects. After a 10-min, 1-h, or 24-h delay two
      different objects were presented; one familiar from the sample phase and one
      novel. An exploration-time difference between the novel and the familiar object
      was interpreted as recognition of the familiar object. We scored the exploration
      times both manually and automatically, and compared the methods. A strong
      discrimination between novel and familiar objects after a 10-min inter-phase
      delay interval and no discrimination after 24h were found in our set-up of the
      spontaneous object recognition test. After a 1-h delay, the pigs still showed a
      significant habituation to the familiar object, but no discrimination was
      observed. Discrimination between the two objects was mainly confined to the first
      half of the test phase, and we observed a high between-subject variation.
      Furthermore, automatic tracking was valid for determination of habituation and
      discrimination parameters but lead to an overestimation of individual
      measurements. We conclude that the spontaneous object recognition test for pigs
      is sensitive to increasing inter-phase delay intervals, and that automatic data
      acquisition can be applied.

PMID- 17524500
TI  - Thyroid disruption in walleye (Sander vitreus) exposed to environmental
      contaminants: cloning and use of iodothyronine deiodinases as molecular
      biomarkers.
AB  - Thyroid hormones play a role in the initiation of ovarian maturation in fish.
      Thus, reports of delayed sexual maturation in female walleye (Sander vitreus)
      exposed to contaminants in the Ottawa River suggest the presence of endocrine
      disrupting chemicals. The objectives of this study were to assess the effects of
      environmental contaminants in the Ottawa River on thyroid hormones of immature
      walleye and to develop a molecular biomarker of thyroid status. Walleye were
      sampled in the Ottawa River at Deep River (reference site), at Riviere Blanche
      (downstream from the Ottawa and Gatineau municipal wastewater treatment plants
      outflows), and at Plaisance (downstream from a pulp and paper mill). Plasma
      thyroid hormone levels were measured by radioimmunoassay. Walleye at Plaisance
      had two-fold elevated levels of thyroxine (T(4)) and 1.5-fold elevated levels
      triiodothyronine (T(3)), whereas the molar ratio of T(3):T(4) was reduced by over
      50% compared to Deep River. Plasma T(3) levels were also elevated by
      approximately 1.5-fold at Riviere Blanche. Three iodothyronine deiodinases, a
      family of enzymes responsible for converting the prohormone T(4) to biologically
      active T(3), as well as for inactivating these two hormones, were partially
      cloned in walleye. A real-time PCR assay of deiodinase expression indicated that
      hepatic mRNA levels of type I and type III deiodinase were not modified between
      sites, whereas they were increased for type II deiodinase at Riviere Blanche as
      compared to the other sites. The response of this novel molecular transcript
      indicates a divergence with that expected based on the effects of experimentally
      induced hyperthyroidism on fish deiodinase expression; additional endpoints are
      therefore necessary to interpret changes in thyroid hormones levels in fish
      exposed to environmental contaminants.

PMID- 17524501
TI  - Pharmacogenomic analyses of targeting the AT-rich malaria parasite genome with AT
      specific alkylating drugs.
AB  - Human malaria parasites, including the most lethal Plasmodium falciparum, are
      increasingly resistant to existing antimalarial drugs. One remarkable opportunity
      to selectively target P. falciparum stems from the unique AT-richness of its
      genome (80% A/T, relative to 60% in human DNA). To rationally explore this
      opportunity, we used drugs (adozelesin and bizelesin) which distinctly target AT
      rich minisatellites and an in silico approach for genome-wide analysis previously
      experimentally validated in human cells [Woynarowski JM, Trevino AV, Rodriguez
      KA, Hardies SC, Benham CJ. AT-rich islands in genomic DNA as a novel target for
      AT-specific DNA-reactive antitumor drugs. J Biol Chem 2001;276:40555-66]. Both
      drugs demonstrate a potent, rapid and irreversible inhibition of the cultured P.
      falciparum (50% inhibition at 110 and 10+/-2.3 pM, respectively). This
      antiparasital activity reflects most likely drug binding to specific super-AT
      rich regions. Relative to the human genome, the P. falciparum genome shows 3.9-
      and 7-fold higher frequency of binding sites for adozelesin and bizelesin,
      respectively. The distribution of these sites is non-random with the most
      prominent clusters found in large unique minisatellites [median size 3.5 kbp of
      nearly pure A/T, with multiple converging repeats but no shared consensus other
      than (A/T)(n)]. Each of the fourteen P. falciparum chromosomes contains only one
      such "super-AT island" located within approximately 3-7.5 kbp of gene-free and
      nucleosome-free loci. Important functions of super-AT islands are suggested by
      their exceptional predicted potential to serve as matrix attachment regions
      (MARs) and a precise co-localization with the putative centromeres. CONCLUSION:
      Super-AT islands, identified as unique domains in the P. falciparum genome with
      presumably crucial functions, offer therapeutically exploitable opportunity for
      new antimalarial strategies.

PMID- 17524502
TI  - Leishmania donovani iron superoxide dismutase A is targeted to the mitochondria
      by its N-terminal positively charged amino acids.
AB  - Many reports have shown that Leishmania species are susceptible to reactive
      oxygen species (ROS) and reactive nitrogen species (RNS)-mediated killing. The
      superoxide dismutase (SOD) is one of the antioxidant defense enzymes important
      for parasite survival through its detoxification of superoxide into hydrogen
      peroxide and oxygen. The mitochondria produce numerous superoxide radicals as a
      by-product of cellular respiration and hence targeting of SODs to the
      mitochondria is critical in maintaining healthy mitochondria. This study examines
      the characteristic determinants for mitochondrial localization of Leishmania
      donovani FeSODA. We show that FeSODA is localized to the mitochondria and that
      the N-terminal 31 amino acid extension is important for its localization.
      Interestingly, further dissection of the 31 amino acid extension revealed that
      the first 8 amino acids of the FeSODA protein are sufficient for targeting to the
      mitochondria. In addition, we found that the four basic amino acid residues
      contained within the N-terminal extension are also important for targeting. These
      studies highlight important features of mitochondrial targeting sequences in
      kinetoplastids.

PMID- 17524504
TI  - The small GTPases Rab5 and RalA regulate intracellular traffic of P-glycoprotein.
AB  - P-glycoprotein (P-gp) is a plasma membrane glycoprotein that can cause multidrug
      resistance (MDR) of cancer cells by acting as an ATP-dependent drug efflux pump.
      The regulatory effects of the small GTPases Rab5 and RalA on the intracellular
      trafficking of P-gp were investigated in HeLa cells. As expected, overexpressed
      enhanced green fluorescent protein (EGFP)-tagged P-gp (P-gp-EGFP) is mainly
      localised to the plasma membrane. However, upon cotransfection of either dominant
      negative Rab5 (Rab5-S34N) or constitutively active RalA (RalA-G23V) the
      intracellular P-gp-EGFP levels increased approximately 9 and 13 fold,
      respectively, compared to control P-gp-EGFP cells. These results suggest that
      Rab5 and RalA regulate P-gp trafficking between the plasma membrane and an
      intracellular compartment. In contrast, coexpression of constitutively active
      Rab5 (Rab5-Q79L) or dominant negative RalA (RalA-S28N) had no effect on the
      localisation of P-gp-EGFP. Furthermore, the intracellular accumulation of
      daunorubicin, a substrate for P-gp, increased significantly with an increased
      intracellular localisation of P-gp-EGFP. These results imply that it may be
      possible to overcome MDR by controlling the plasma membrane localisation of P-gp.

PMID- 17524503
TI  - MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism.
AB  - beta-Catenin binds to the cytoplasmic region of the type 1 membrane glycoprotein
      MUC1. In the current study, we utilized HEK293T cells expressing the full-length
      MUC1 protein, or a CD8/MUC1 fusion protein containing only the MUC1 cytoplasmic
      tail, to investigate the effects of beta-catenin binding to MUC1 on downstream
      beta-catenin-dependent events. Compared with HEK293T cells transfected with empty
      vector or CD8 alone, expression of the MUC1 cytoplasmic tail inhibited beta
      catenin binding to E-cadherin, decreased translocation of beta-catenin into the
      nucleus, reduced activation of the LEF-1 transcription factor, and blocked
      expression of the cyclin D1 and c-Myc proteins. Furthermore, expression of MUC1
      was associated with decreased cell proliferation, either in the context of the
      transfected HEK293T cells, or when comparing wild type (Muc1(+/+)) vs. knockout
      (Muc1(-/-)) mouse primary tracheal epithelial cells. We conclude that MUC1
      inhibits cell proliferation through a beta-catenin/LEF-1/cyclin D1/c-Myc pathway.

PMID- 17524505
TI  - Comparative evaluation of biofilm disinfectant efficacy tests.
AB  - Regulatory agencies are receiving registration applications for unprecedented,
      antibiofilm label claims for disinfectants. Reliable, practical, and relevant
      laboratory biofilm test methods are required to support such claims. This
      investigation describes the influence of fluid dynamics on the relevancy of a
      laboratory test. Several disinfectant formulations were tested using three
      different biofilm testing systems run side-by-side: the CDC biofilm reactor
      system that created turbulent flow (Reynolds number between 800 and 1850), the
      drip flow biofilm reactor system that created slow laminar flow (Reynolds number
      between 12 and 20), and the static biofilm system that involved no fluid flow.
      Each comparative experiment also included a dried surface carrier test and a
      dried biofilm test. All five disinfectant tests used glass coupons and followed
      the same steps for treatment, neutralization, viable cell counting, and
      calculating the log reduction (LR). Three different disinfectants, chlorine, a
      quaternary ammonium compound, and a phenolic, were each applied at two
      concentrations. Experiments were conducted separately with Pseudomonas aeruginosa
      and Staphylococcus aureus and every experiment was independently repeated. The
      results showed that biofilm grown in the CDC reactor produced the smallest LR,
      the static biofilm produced the largest LR, and biofilm grown in the drip flow
      reactor produced an intermediate LR. The differences were large enough to be of
      practical importance. The dried surface test often produced a significantly
      higher LR than the tests against hydrated or dried biofilm. The dried biofilm
      test produced LR values similar to those for the corresponding hydrated biofilm
      test. These results show that the efficacy of a disinfectant must be measured by
      using a laboratory method where biofilm is grown under fluid flow conditions
      similar to the environment where the disinfectant will be applied.

PMID- 17524506
TI  - Expression patterns of the hypoxia-related genes osteopontin, CA9,
      erythropoietin, VEGF and HIF-1alpha in human glioma in vitro and in vivo.
AB  - BACKGROUND AND PURPOSE: To identify molecular markers of tumor hypoxia and
      potential therapeutic targets in glioblastoma (GBM), we investigated the hypoxia
      related expression of osteopontin (OPN), carbonic anhydrase 9 (CA9),
      erythropoietin (EPO), vascular endothelial growth factor (VEGF) and hypoxia
      inducible factor-1alpha (HIF-1alpha) in vitro in human GBM cell lines and in vivo
      in human tumor samples of GBM, compared to low-grade astrocytoma (LGA). MATERIALS
      AND METHODS: Expression of the hypoxia-induced genes OPN, CA9, EPO, VEGF and HIF
      1alpha was analyzed in three GBM cell lines, GaMG, U373 and U251, under in vitro
      hypoxia (1, 6 or 24h at 5%, 1% or 0.1% O(2)) and in tumor samples from two
      patient groups with LGA and GBM (n=15 each), at the mRNA level (semiquantitative
      RT-PCR). Selected conditions and representative tumor samples were also evaluated
      at the protein level by Western blot. RESULTS: OPN and CA9 mRNA was most
      consistently upregulated in relation to severity and duration of in vitro
      hypoxia. In tumor samples, mean expression levels (LGA vs. GBM, normalized to
      mean expression in normal brain) were 1.71 vs. 4.57 (p<0.001) for OPN, 1.11 vs.
      3.35 (p<0.001) for CA9, 2.79 vs. 5.28 (not significant, n.s.) for Epo, 1.13 vs.
      2.0 (p=0.007) for VEGF and 0.97 vs. 0.97 (n.s.) for HIF-1alpha. In tumor samples,
      GBM showed a particularly strong protein expression of OPN. CONCLUSIONS: Among a
      panel of known hypoxia-inducible genes, OPN and CA9 emerge as most consistently
      induced by in vitro hypoxia in human GBM cell lines and most specifically
      expressed in patient GBM tumor tissue, rendering these two genes attractive
      targets for hypoxia-directed treatment approaches.

PMID- 17524507
TI  - Impact of brain-behavior phenotypying of genetically-engineered mice on research
      of neuropsychiatric disorders.
AB  - Despite massive research efforts, the exact pathogenesis and pathophysiology of
      psychiatric disorders, such as schizophrenia and bipolar disorder, remain largely
      unknown. Animal models can serve as essential tools for investigating the
      etiology and treatment of such disorders. Since the introduction of gene
      targeting techniques, the functions of more than 10% of all known mouse genes
      have been investigated by creating mutant mice. Some of these mutant mouse
      strains were found to exhibit behavioral abnormalities reminiscent of human
      psychiatric disorders. In this review, we discuss the general requirements for
      animal models of human psychiatric disorders. We also outline our unique approach
      of extrapolating findings in mice to humans, and present studies on forebrain
      specific calcineurin knockout mice as an example. We also discuss the impact of a
      large-scale mouse phenotyping on studies of psychiatric disorders and the
      potential utility of an "animal-model-array" of psychiatric disorders for the
      development of suitable therapeutic agents.

PMID- 17524508
TI  - Threshold-like pattern of neuronal activation in the hypothalamus during
      treadmill running: establishment of a minimum running stress (MRS) rat model.
AB  - Despite the indication that the hypothalamo-pituitary-adrenal (HPA) axis is
      activated during treadmill running, there have not been any studies focusing on
      the relationship between exercise intensity and region-specific neural activities
      in hypothalamus. To address this, rats were subjected to 30 min of running,
      either at middle (supra-LT, 25 m min(-1)) or low speeds (sub-LT, 15 m min(-1)),
      and c-Fos-(+) cells were counted and compared with control rats. Significant
      increases in blood glucose and lactate levels, and plasma ACTH and osmolality
      levels were observed during supra-LT running. Only supra-LT running significantly
      increased c-Fos induction in various hypothalamic regions, namely, the medial
      preoptic area (MPO), periventricular nucleus (Pe), suprachiasmatic nucleus (SCN),
      supraoptic nucleus (SON), parvocellular division of the paraventricular nucleus
      (pPVN), anterior hypothalamic area (AH), arcuate nucleus (ARC) and posterior
      hypothalamic nucleus (PH). However, sub-LT caused no effect on c-Fos
      accumulation. This indicates that the hypothalamus responds uniquely to running
      in a threshold-like pattern distinct from the speed-dependent pattern previously
      reported for the medulla oblongata [Ohiwa et al., 2006a,b]. In addition, these
      results showed a physiologic basis for mild exercise useful for establishing our
      minimum running stress (MRS) rat model, or the running conditions that minimize
      the activation of the HPA axis.

PMID- 17524509
TI  - Genetic structure and evolution of natural populations of viruses causing the
      tomato yellow leaf curl disease in Spain.
AB  - The population structure and genetic variation of two begomoviruses: tomato
      yellow leaf curl Sardinia virus (TYLCSV) and tomato yellow leaf curl virus
      (TYLCV) in tomato crops of Spain were studied from 1997 until 2001. Restriction
      digestion of a genomic region comprised of the CP coat protein gene (CPR) of 358
      TYLC virus isolates enabled us to classify them into 14 haplotypes. Nucleotide
      sequences of two genomic regions: CPR, and the surrounding intergenic region
      (SIR) were determined for at least two isolates per haplotype. SIR was more
      variable than CPR and showed multiple recombination events whereas no
      recombination was detected within CPR. In all geographic regions except Murcia,
      the population was, or evolved to be composed of one predominant haplotype with a
      low genetic diversity (<0.0180). In Murcia, two successive changes of the
      predominant haplotype were observed in the best studied population. Phylogenetic
      analysis showed that the TYLCSV sequences determined clustered with sequences
      obtained from the GenBank of other TYLCSV Spanish isolates which were clearly
      separated from TYLCSV Italian isolates. Most of our TYLCV sequences were similar
      to those of isolates from Japan and Portugal, and the sequences obtained from
      TYLCV isolates from the Canary island of Lanzarote were similar to those of
      Caribbean TYLCV isolates.

PMID- 17524510
TI  - Major amino acid sequence variants of viral vascular endothelial growth factor
      are functionally equivalent during Orf virus infection of sheep skin.
AB  - Orf virus infection causes a contagious pustular dermatitis characterized by
      extensive vascular changes that have been linked to a virally encoded vascular
      endothelial growth factor (VEGF). The VEGF genes of different strains of orf
      virus can vary extensively in amino acid sequence. Functional analyses of two
      major variant VEGF proteins derived from orf virus strains, NZ2 and NZ7, have
      revealed quantitative differences in biological activities and receptor binding
      specificities suggesting that these viral VEGFs could have different roles in the
      pathology of orf virus infection. In this study, we show that both orf virus
      strains express equivalent levels of the viral VEGF variants and during infection
      of sheep skin induce comparable levels of vascularization, edema, epidermal rete
      ridge and scab formation. Recombinants of orf virus NZ2 and NZ7 strains in which
      the variant VEGF genes were disrupted showed markedly reduced vascular changes
      and evidence of partially attenuated viral growth. These results demonstrate that
      despite substantial differences in sequence and biological activity in vitro,
      these virally expressed virulence factors are functionally equivalent in their
      natural host, contributing equally to orf virus pathology.

PMID- 17524511
TI  - In vivo imaging of cidofovir treatment of cowpox virus infection.
AB  - Variola virus and other members of the genus Orthopoxviruses constitute a
      prominent bioterrorism and public health threat. Treatment with the anti-viral
      drug cidofovir inhibits replication of orthopoxviruses in vitro and in vivo. In
      this study, we visualized the effect of cidofovir on viral kinetics in
      orthopoxvirus infected mice by using whole-body fluorescence imaging (FI). We
      engineered a cowpox virus (CPV) expressing the enhanced green fluorescent protein
      (GFP). Single-step growth curves and calculated 50% lethal doses (LD(50)) of wild
      type CPX (Wt-CPV) and GFP-expressing CPX (GFP-CPV) were comparable. Whole-body FI
      first detected GFP fluorescence in the mesenteric tissue of untreated animals on
      post-infection day (PID) 1. On PID 3 GFP signal was detected throughout the
      mesentery, in all abdominal organs by PID 5 and in most major organs, except for
      the heart and brain by PID 6. Infected animals treated with 25mg/kg of cidofovir
      also began showing signs of viral replication on PID 1, however, the fluorescent
      signal was limited only to discrete foci throughout the course of the infection.
      This work describes the first use of an established Orthopox model of infection
      to evaluate drug efficacy and track virus progression on a macroscopic level.

PMID- 17524512
TI  - Detection of Dobrava hantaviruses in Apodemus agrarius mice in the Transdanubian
      region of Hungary.
AB  - Dobrava hantavirus (DOBV) belongs to the genus Hantavirus of the family
      Bunyaviridae, and is carried by yellow necked and striped field mice (Apodemus
      flavicollis and Apodemus agrarius), respectively. The aim of this study was to
      detect and genetically characterize new DOBV strains in rodents captured in the
      Transdanubian region of Hungary. Rodent corpses were dissected and lung tissues
      were used for hantavirus detection by SYBR Green-based real-time RT-PCR using
      specific primers located in the S-segment of the virus genome. A total of 22
      captured animals of the Apodemus species were tested for the presence of DOBV.
      Three out of the 22 mice were positive. Phylogenetic and molecular sequence
      analyses showed that Hungarian DOBVs were most closely related to those viruses
      detected from A. agrarius mice in Slovenia. Based on our new data from the region
      we concluded that extended reservoir studies would be necessary in the future.

PMID- 17524513
TI  - Codon usage and replicative strategies of hepatitis A virus.
AB  - Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has many biological
      characteristics that distinguish it from other members of the Picornaviridae
      family. Among these it is worth of note the need for an intact eIF4G factor for
      the initiation of translation and thus the inability to shut down host protein
      synthesis by a similar mechanism as in other picornaviruses. Consequently, HAV
      must inefficiently compete for the cellular translational machinery and this may
      explain its poor growth in cell culture. In this context of virus/cell
      competition HAV has strategically adopted a naturally highly deoptimized codon
      usage. Accordingly, a low protein synthesis may be expected with those proteins
      involved in RNA replication existing at limiting concentrations. Thus, a very low
      translation rate and a very low RNA replication rate may play a role in escaping
      to host cell defenses, allowing the virus to grow in a quiescent way. This could
      explain the high specific infectivity of HAV in spite of its naturally
      deoptimized codon usage, which would indicate non-abortive infections due to the
      antiviral cell response. Additionally, the deoptimized codon usage conveys in the
      use of abundant and rare codons. Many clusters of such rare codons are present in
      the capsid surface playing a seminal role in the highly cohesive stability of the
      HAV virion. Thus, the slow translation rate, resulting from the accumulation of
      rare codons, is likely to contribute to the highly stable viral capsid necessary
      for a prolonged survival outside the host body.

PMID- 17524514
TI  - Enhanced circulation time and antitumor activity of doxorubicin by comblike
      polymer-incorporated liposomes.
AB  - Polymer incorporation on liposomal membranes has been extensively studied as a
      method of enhancing the circulation time of liposomes in the bloodstream. In this
      study, we investigated the in vitro and in vivo characteristics of liposomes
      whose surface was modified using a comblike polymer comprised of a poly(methyl
      methacrylate) (PMMA) backbone and short poly(ethylene oxide) (PEO) side chains.
      Doxorubicin (DOX)-loaded liposomes incorporating with the comblike polymer were
      prepared and their circulation time, biodistribution and antitumor activity were
      evaluated in B16F10 melanoma tumor-bearing mice. The circulation half-life time
      in the bloodstream of the comblike polymer-incorporated liposomes (CPILs) was
      approximately 14- or 2-fold higher than those of the conventional or
      polyethyleneglycol-fixed liposomes (PEG-liposomes), respectively. Additionally,
      in the biodistribution assay, the accumulation of the CPILs in the tumor was
      higher than those of the other liposomes. Based on this result, the antitumor
      activities of the CPILs were higher than those of conventional liposome
      formulation of DOX or free DOX due to the higher passive targeting efficiency of
      the long-circulating CPILs to tumor. This study suggests that the incorporation
      of the comblike polymer on the liposomal membrane is a promising tool to further
      improve circulation time of liposomes in tumor-bearing mice.

PMID- 17524515
TI  - Passive diffusion of polymeric surfactants across lipid bilayers.
AB  - Self-assembling polymeric surfactant, mmePEG(750)P(CL-co-TMC) [monomethylether
      poly(ethylene glycol)(750)-poly(caprolactone-co-trimethylene carbonate)],
      increases drug solubility and crosses an enterocyte monolayer both in vitro and
      in vivo. The aims of the present work were to investigate whether mmePEG(750)P(CL
      co-TMC) polymers can diffuse passively through lipid bilayer using parallel
      artificial membrane permeability assay (PAMPA) and affect membrane properties
      using liposomes as model. The mmePEG(750)P(CL-co-TMC) polymer was able to cross
      by passive diffusion an enterocyte-mimicking membrane in PAMPA at concentration
      which did not perturb membrane integrity. A weak rigidification associated with a
      low increase in permeability of liposomal lipid bilayers was observed. These data
      suggest that polymeric surfactants can cross the lipid membrane by passive
      diffusion and interact with lipid bilayers.

PMID- 17524517
TI  - Prevalence of the metabolic syndrome in Peruvian Andean hispanics: the PREVENCION
      study.
AB  - Data regarding the prevalence of metabolic syndrome (MTS) in Andean populations
      are limited. We evaluated the prevalence of MTS according to American Heart
      Association/National Heart, Lung and Blood Institute criteria among 1878 subjects
      in the PREVENCION study in Peru. In women, the most common component was low HDL
      cholesterol (60.9%) followed by abdominal obesity (36.9%). In men, the most
      common component was elevated triglycerides (52.0%) followed by low HDL
      cholesterol (32.5%), whereas the prevalence of abdominal obesity was 14%.
      Abnormal fasting glucose was the least common component in men (5.4%) and women
      (5.0%). The prevalence of MTS was significantly higher in women compared to men
      (23.2% versus 14.3%) and increased steeply with age, particularly in women
      (p<0.0001). Using body mass index (BMI>or=30kg/m2) instead of waist circumference
      as a component of the MTS lead to equivalent prevalence estimates of MTS in men
      but significantly underestimated the prevalence in women. The MTS is highly
      prevalent among Peruvian Andeans, particularly in older women. The pattern of MTS
      components in this Andean population is characterized by a high prevalence of
      dyslipidemia and a relatively low prevalence of elevated fasting glucose. Further
      studies are required to characterize genetic and environmental determinants of
      these patterns.

PMID- 17524518
TI  - Public policies and the problematic USA population health profile.
AB  - International interest in the social determinants of health and their public
      policy antecedents is increasing. Despite evidence that the USA presents one of
      the worst population health profiles and public policy environments in support of
      health among wealthy developed nations - a result of systemic inequities in
      income, influence, and power - the USA public health gaze is firmly - and
      narrowly - focused on issues of access to health care, racial and ethnic
      disparities in healthcare, and individual behavioral risk factors. Reasons for
      the USA's neglect of structural and public policy issues are explored and Ten
      Tips for American Public Health Researchers and Workers are presented.

PMID- 17524519
TI  - Insertional polymorphisms: a new lease of life for endogenous retroviruses in
      human disease.
AB  - Human endogenous retroviruses (HERVs) result from ancestral infection by
      infectious viruses over millions of years of primate evolution. Some are
      transcriptionally active, express proteins and therefore have the potential to
      cause disease. Here we review the controversial attempts to link them with cancer
      and autoimmunity. The main difficulty is that most HERVs investigated to date are
      present at the same locus in 100% of the population. However, a new class of
      insertionally polymorphic HERV-K family members, present in a minority of
      individuals, has recently been described. We propose that insertionally
      polymorphic HERVs could be novel genetic risk factors and hence provide a new
      lease of life for research into HERVs and disease.

PMID- 17524520
TI  - Heartening news for head muscle development.
AB  - Branchiomeric craniofacial muscles differ from all other skeletal muscles with
      respect to embryological origin, motor innervation and upstream activators of
      myogenesis. A series of recent studies has revealed a striking juxtaposition and
      overlapping genetic program of craniofacial skeletal muscle progenitor cells with
      a population of cells giving rise to cardiac muscle. The divergent myogenic fates
      of adjacent progenitor cells revealed by these data provide a new framework for
      the study of craniofacial myogenesis.

PMID- 17524521
TI  - Homeostasis: beyond Curt Richter.
AB  - Curt Richter introduced behavioral control into the concept of homeostasis,
      thereby opening entire fields of research. The prevailing dogma, and the
      techniques he used, conspired to lead Richter and others to interpret regulation
      in strict negative feedback terms. Although this point of view continues to be
      embraced by many contemporary biologists, we believe that prevailing sentiment
      favors a broader view in which organisms integrate anticipatory pre-emptive
      control over regulated variables whenever possible.

PMID- 17524522
TI  - Ontogeny of PAC1-R and VPAC1-R in the frog, Rana esculenta.
AB  - The distribution of pituitary adenylate cyclase-activating polypeptide (PACAP)
      and PACAP receptors in the brain of amphibians has been previously described. In
      the present study, we have investigated the ontogeny of the selective PACAP
      receptor, PAC1-R, and the PACAP-vasoactive intestinal polypeptide (VIP) mutual
      receptor, VPAC1-R, in frog embryos by whole-mount in situ hybridization
      histochemistry. At stage 20, expression of PAC1-R and/or VPAC1-R mRNAs was
      detected in the brain, the auditory vesicles, the external gills, the buds of the
      lateral lines and the coelomatic cavity. At stage 25, PAC1-R and/or VPAC1-R mRNAs
      were observed in the buds of the orbital lateral line, the pancreas and heart. At
      stage 30, PAC1-R and VPAC1-R mRNAs were widely distributed in the telencephalon
      and diencephalon as well as in the bud of the lateral line, the heart and the
      pancreas. The anatomical distribution of PAC1-R and VPAC1-R mRNAs, although
      similar, did not totally overlap, indicating that PACAP and VIP may exert
      differential effects in frog during development.

PMID- 17524523
TI  - Transient forebrain ischemia effects FAK-coupled signaling in gerbil hippocampus.
AB  - Focal adhesion kinase (FAK) is thought to play a major role in transducing
      extracellular matrix (ECM)-derived survival signals into cells. The function of
      FAK is linked to its autophosphorylation at Tyr-397 and then recruitment of
      several effector molecules. Thus, modulation of FAK activity may affect several
      intracellular signaling pathways and may participate in a variety of pathological
      settings. In the present study, we investigated the effect of short-term 5 min
      forebrain ischemia on levels and Tyr-397 phosphorylation of focal adhesion kinase
      and the interaction of this enzyme with Src protein tyrosine kinase and adapter
      protein p130Cas, involved in FAK-mediated signaling pathway in gerbil
      hippocampus. The total amount of focal adhesion kinase as well as its Tyr-397
      phosphorylation declined substantially between 24 and 48 h after the insult,
      particularly in CA1 region of hippocampus. Concomitantly, a decreased amount of
      FAK/Src kinase complex has been observed. These data indicate that inhibition of
      FAK/Src-coupled signaling pathway may participate in the ischemia-induced
      neuronal degeneration in gerbil hippocampus. The temporal profile of FAK down
      regulation in CA1 area coincides with metalloproteinases (MMPs) activation. These
      results suggest that extracellular proteolysis might belong to the mechanisms
      which govern the FAK-coupled pathway in ischemic hippocampus.

PMID- 17524524
TI  - Basic fibroblast growth factor: lysine 134 is essential for its neuroprotective
      activity.
AB  - Basic fibroblast growth factor (bFGF) is a heparin-binding growth factor known to
      cause cell proliferation, angiogenesis and neuroprotection. We have performed
      site-directed mutagenesis to identify the amino acids that are essential for
      heparin/growth factor interaction and for neuroprotection. Binding to heparin
      acrylic beads was markedly reduced when lysine in position 134 of bFGF was
      replaced by alanine. Wildtype (wt)-bFGF was shown to protect rat primary cultures
      of embryonic hippocampal neurons against damage caused by staurosporine and to
      reduce the infarct size in mice after focal cerebral ischemia. These
      neuroprotective effects of wt-bFGF could not be shown for the mutant bFGF(K134A).
      Furthermore, phosphorylation of Akt and ERK1/2 was significantly reduced in
      cultured neurons treated with bFGF(K134A) indicating diminished intracellular
      signaling compared to neurons treated with wt-bFGF. In conclusion, lysine at
      position 134 of bFGF is essential for bFGF to bind heparin, then to interact with
      its receptor and, subsequently, to protect neurons against damage.

PMID- 17524525
TI  - A blueberry-enriched diet provides cellular protection against oxidative stress
      and reduces a kainate-induced learning impairment in rats.
AB  - Young male Fischer-344 rats were fed a diet containing 2% blueberry (BB) extract
      or control diet for at least 8 weeks and then received bilateral hippocampal
      injections of kainic acid (KA 200 ng/0.5 microl) or phosphate buffered saline
      (PBS). One week later rats were trained in one-way active footshock avoidance in
      a straight runway followed the next day by training in a footshock motivated 14
      unit T-maze with documented sensitivity to hippocampal glutamatergic
      manipulations. Based on analyses of several performance variables, KA-treated
      rats exhibited clearly impaired learning performance; however, the BB diet
      significantly reduced this impairment. Supporting the behavioral findings,
      stereological assessment of CA1 pyramidal neurons documented greater neuronal
      loss in KA-treated controls compared to KA-treated rats on the BB diet. In an in
      vitro experiment, FaO cells grown in medium supplemented with serum from BB-fed
      rats had enhanced viability after exposure to hydrogen peroxide. These findings
      suggest that BB supplementation may protect against neurodegeneration and
      cognitive impairment mediated by excitotoxicity and oxidative stress.

PMID- 17524526
TI  - Synthesis and characterization of novel azo-morphine derivatives for possible use
      in abused drugs analysis.
AB  - A new simple and fast spectroscopic method was presented as a new marker for
      heroin use. Novel azo-morphine derivatives with spectroscopic absorption peaks
      ranging from 330-470 nm, were synthesized by the coupling of morphine (M) and 6
      acetyl morphine (6-AM) with freshly prepared diazonium salt of aniline
      hydrochloride at 0 degrees C. However, no reaction was observed with codeine
      under the same reaction conditions. Separation of azo dyes was performed by TLC
      using tetrahydrofuran and dichloromethane in the ratio 1:1. The chemical
      structure of the products was established by their microanalysis, NMR, IR, UV
      vis, and mass spectroscopies. Electronic absorption and excitation spectra of the
      dyes were measured in solvents of different polarities. The dyes exhibited
      positive solvatochromism, i.e., a bathochromic band shift as the solvent polarity
      is increased. Also, the fluorescence quantum yield was sensitive to the polarity
      and the pH of the medium. The UV-vis spectroscopy of spiked compounds in human
      urine samples was also reported. The drugs (M, 6-AM and mixture of both) were
      coupled with freshly prepared diazonium salt even at very low concentration of
      the drugs 10(-9)M.

PMID- 17524527
TI  - Still crazy after all these years.

PMID- 17524528
TI  - Infant vaccination coverage in 2005 and predictive factors for complete or valid
      vaccination in Flanders, Belgium: an EPI-survey.
AB  - To assess changes in infant vaccination coverage in Flanders since 1999, an EPI
      survey was performed in 2005. The parents of 1354 children aged 18-24 months were
      interviewed at home and the vaccination documents were checked. Several factors
      possibly related to vaccination status were examined with parametric and non
      parametric methods. The coverage rate of recommended vaccines, i.e.
      poliomyelitis, tetanus-diphtheria-pertussis, H. influenzae type b (Hib),
      hepatitis B, measles-mumps-rubella (MMR) and meningococcal C, reached at least
      92.2%, which is a significant rise for MMR, hepatitis B and Hib since 1999. The
      vaccinating physician, the employment situation of the mother and the family
      income were significant predictive factors for having received all recommended
      vaccine doses (complete schedule), also when considering only doses that were
      according to minimal age and interval criteria (valid schedule).

PMID- 17524529
TI  - A new approach to the definition of seroconversion following vaccination in a
      population with high background antibody concentrations.
AB  - Licensure of meningitis vaccines is increasingly being made on the basis of
      safety and immunogenicity. For meningococcal vaccines, a measure of
      immunogenicity is seroconversion, usually defined as a four-fold increase in rSBA
      titre. However, this definition is likely to underestimate seroconversion in
      settings with high background immunity. Using data from a study of the
      immunogenicity of meningococcal polysaccharide vaccines undertaken in Ghana, a
      logistic regression model to estimate the probability of seroconversion as a
      function of pre-vaccination titre has been developed. The seroconversion rate
      (91%) based on a variable-fold increase in rSBA titre derived from the model was
      a more plausible estimate of immunogenicity than the seroconversion rate (32%)
      based on the fixed four-fold increase in rSBA.

PMID- 17524530
TI  - Enhanced protection against pneumococcal infection elicited by immunization with
      the combination of PspA, PspC, and ClpP.
AB  - Immunization with a combination of several virulence-associated proteins is one
      of the strategies of developing effective protein-based vaccines to enhance the
      protection against Streptococcus pneumoniae. In this study, we evaluated the
      protection effects against pneumococcal infection caused by S. pneumoniae TIGR4
      in BALB/c mice immunized with either single pneumococcal surface protein A
      (PspA), pneumococcal surface protein C (PspC), the caseinolytic protease (ClpP)
      or their combinations. The median survival times for mice immunized with single
      antigen or their combinations were significantly longer than that for mice
      treated with adjuvant alone. Mice treated with a combination of three antigens
      survived significantly longer than those that received either single or two
      antigens. The highest survival rate of the various groups of mice was observed
      with the combination of three antigens, this survival rate was significantly
      different from those for mice that received either single antigen or the
      combinations of two antigens except the mixture of ClpP and PspA. In the
      experiment of passive immunization with hyperimmune serums containing their
      specific polyclonal antibodies (anti-PspA serum, anti-PspC serum, anti-ClpP
      serum), the median survival times for mice immunized with hyperimmune serums
      containing specific polyclonal antibodies were significantly longer than that for
      control mice, the treatment of serum containing only one single polyclonal
      antibody could not provide higher survival rate than control serum. However, the
      survival rates for mice treated with the serums containing combined polyclonal
      antibodies were significantly higher than those for mice treated with either
      control serum or anti-PspA serum alone. Immunization with the combination of
      three hyperimmune serums also provided the best protection against S. pneumoniae.
      Compared to mice treated with serum containing single polyclonal antibody, the
      survival rate for mice treated with serums containing three polyclonal antibodies
      was significantly higher but was not different from those for mice treated with
      serums containing two polyclonal antibodies. Our findings provided evidence that
      a mixture of PspA, PspC, and ClpP or their polyclonal antibodies could enhance
      the protection against pneumococcal infection acting a synergetic effect.

PMID- 17524531
TI  - Generation of long-lived plasma cells to serogroup B Neisseria meningitidis after
      murine immunisation with an outer membrane protein vaccine.
AB  - There is no universal vaccine against serogroup B meningococcus (Men B). We
      investigated the development of spleen and bone marrow-specific IgG-secreting
      plasma cells (ASC) in mice immunised with the Cuban outer membrane protein (OMP)
      vaccine (VA-MENGOC-BC). Bone marrow was the predominant anatomical site of
      specific ASC and showed constant ASC levels (approximately 4%) at each time point
      analysed, indicating the production of long-lived ASC. A mean of 2.36 and 0.35%
      of Men B ASC was detected in spleen after the third dose and 2 months later,
      respectively, indicating a short-lived population. The data suggest that a short
      lived ASC population in spleen was responsible for serum IgG anti-OMP while ASC
      from bone marrow produced persistent bactericidal antibodies against the vaccine
      strain. The response to the booster dose was consistent with development of
      memory B cells by primary vaccination.

PMID- 17524532
TI  - Antigenicity of infectious pancreatic necrosis virus VP2 subviral particles
      expressed in yeast.
AB  - Infectious pancreatic necrosis (IPN) virus, the etiologic agent of infectious
      pancreatic necrosis in salmonid fish, causes significant losses to the
      aquaculture industry. The gene for the viral capsid protein (VP2) was cloned into
      a yeast expression vector and expressed in Saccharomyces cerevisae. Expression of
      the capsid gene in yeast resulted in formation of approximately 20nm subviral
      particles composed solely of VP2 protein. Anti-IPNV antibodies were detected in
      rainbow trout vaccinated either by injection of purified VP2-subviral particles
      (rVP2-SVP) or by feeding recombinant yeast expressing rVP2-SVP. Challenge of rVP2
      SVP immunized trout with a heterologous IPNV strain and subsequent viral load
      determination demonstrated that both injection and orally vaccinated fish had
      lower IPNV loads than naive or sham-vaccinated fish. This study demonstrates the
      ability of rVP2-SVPs to induce a specific immune response and the ability of
      immunized fish to reduce the viral load after an experimentally induced IPNV
      infection.

PMID- 17524533
TI  - A safe and accurate technique for transbuccal incisions.

PMID- 17524534
TI  - Review of maxillofacial injuries in Chennai, India: a study of 2748 cases.
AB  - We reviewed the medical records of 2748 patients treated for maxillofacial
      injuries at Sri Ramachandra Medical and Dental College and Hospital between
      January 1999 and December 2005. 1332 (42%) had soft tissue injuries, 1176 (37%)
      had mid face fractures, and 512 (16%) had mandibular fractures. Most patients
      with midface fractures had fractures of the zygomaticomaxillary region 422 (36%),
      while fractures of the parasymphyseal region were more common in the mandible 156
      (31%). Most patients were in the 21-30 year-old age group, and the male:female
      ratio was 3.7:1. Road crashes, particularly involving motorcycles, accounted for
      1710 (62%), with a high prevalence during the month of September and on
      Saturdays.

PMID- 17524535
TI  - Nd:YAG laser biostimulation of bisphosphonate-associated necrosis of the jawbone
      with and without surgical treatment.
AB  - Bisphosphonate-associated osteonecrosis was first reported in 2003 and is getting
      common. Size of lesions, symptoms, and duration of time between starting
      bisphosphonates and the development of bone necrosis vary. There is currently no
      effective treatment. We describe our preliminary results with 19 patients
      affected by bisphosphonate-associated osteonecrosis of the jaws who were treated
      conventionally with surgical or medical treatment alone or in combination with
      neodimium: yttrium-aluminium-garnet (Nd:YAG) laser. Clinical variables such as
      symptoms, presence of pus, and closure of mucosal flaps before and after
      treatment were evaluated to establish the effect of the laser irradiation. We
      treated nine patients with laser biostimulation with or without surgical
      treatment, and in this group there were eight clinical successes and one
      symptomatic improvement, with a clinical finding better than ones without laser
      biostimulation (ten patients, five clinical successes, and one symptomatic
      improvement).

PMID- 17524536
TI  - Hydrodynamic and geochemical constraints on pesticide concentrations in the
      groundwater of an agricultural catchment (Brevilles, France).
AB  - The monitoring of a spring and seven piezometers in the 3km(2) Brevilles
      agricultural catchment (France) over five and a half years revealed considerable
      spatial and temporal variability in the concentrations of atrazine and its
      metabolite deethylatrazine (both systematically quantified at the outlet spring):
      maximum 0.97 and 2.72microgL(-1), mean 0.19 and 0.59microgL(-1), respectively.
      Isoproturon, the pesticide applied in the greatest amount, was detected in only
      10 of the 133 samples. These observations can only partly be explained by land
      use and intrinsic pesticide properties. Geochemical measurements and tritium
      dating showed the importance of the stratification of the sandy saturated zone
      and the buffer function of the unsaturated limestone. Principal component
      analysis on 39 monthly data series of atrazine, deethylatrazine, nitrate,
      chloride and piezometric levels revealed a temporal structuring of the data
      possibly reflecting the existence within the aquifer of two different reservoirs
      with time-variable contributions.

PMID- 17524537
TI  - Ozone uptake (flux) as it relates to ozone-induced foliar symptoms of Prunus
      serotina and Populus maximowiziixtrichocarpa.
AB  - Field studies were conducted during 2003 and 2004 from early June to the end of
      August, at 20 sites of lower or higher elevation within north-central
      Pennsylvania, using seedlings of black cherry (Prunus serotina, Ehrh.) and ramets
      of hybrid poplar (Populus maximowiziixtrichocarpa). A linear model was developed
      to estimate the influence of local environmental conditions on stomatal
      conductance. The most significant factors explaining stomatal variance were tree
      species, air temperature, leaf vapor pressure deficit, elevation, and time of
      day. Overall, environmental factors explained less than 35% of the variation in
      stomatal conductance. Ozone did not affect gas exchange rates in either poplar or
      cherry. Ozone-induced foliar injury was positively correlated with cumulative
      ozone exposures, expressed as SUM40. Overall, the amount of foliar injury was
      better correlated to a flux-based approach rather than to an exposure-based
      approach. More severe foliar injuries were observed on plants growing at higher
      elevations.

PMID- 17524538
TI  - The role of social support and integration for understanding socioeconomic
      disparities in self-rated health and hypertension.
AB  - This paper examines socioeconomic (socioeconomic status, SES) disparities in self
      rated health and hypertension among 29,816 US adults aged 25 and older using data
      from the 2001 wave of the National Health Interview Survey. Our purpose is to
      examine how influential measures of social support and social integration are for
      each health outcome, and whether support and integration operate by mediating, or
      buffering, the effects of SES on health. Multivariate regression models show no
      significant influence of emotional support, but do indicate that many aspects of
      social integration are directly associated with self-rated health and
      hypertension, although these measures do not mediate the relationship between SES
      and health. However, interaction tests show substantial evidence that measures of
      social integration buffer some of the negative effects of low SES, particularly
      the negative influence of not working on self-rated health. In addition, findings
      indicate potential evidence of help-seeking behavior among adults who did not
      finish high school or who report financial barriers to medical care. Overall, our
      findings suggest that social programs designed to foster social integration
      (e.g., free or low-cost bus fare to promote visits with friends and family) may
      improve health among persons with low levels of education, who are not working,
      or who have problems accessing medical care because of financial problems.

PMID- 17524539
TI  - Studies on the in vitro absorption of spice principles--curcumin, capsaicin and
      piperine in rat intestines.
AB  - A comparative evaluation of the absorbability of three structurally similar and
      physiologically active spice principles in an in vitro system consisting of
      everted rat intestinal sacs was made. When everted sacs of rat intestines were
      incubated with 50-1000 microg of curcumin in 10 ml incubation medium, absorption
      of the spice principle was maximum at 100 microg concentration. The amount of
      absorbed curcumin present in the serosal fluid was negligible. This and the
      comparatively lower recovery of the original compound suggested that curcumin to
      some extent undergoes a modification during absorption. For similar
      concentrations of added piperine, about 44-63% of piperine disappeared from the
      mucosal side. Absorption of piperine which was maximum at 800 microg per 10 ml
      was about 63%. The absolute amounts of piperine absorbed in this in vitro system
      exceeded the amounts of curcumin. The absorbed piperine could be traced in both
      the serosal fluid and in the intestinal tissue, indicating that piperine did not
      undergo any metabolic change during the process of absorption. 7-12% of the
      absorbed piperine was found in the serosal fluid. When everted sacs of rat
      intestines were incubated with 10-500 microg of capsaicin, a maximum of 82-88%
      absorption could be seen in the lower concentrations, and the amount of absorbed
      capsaicin did not proportionately increase at higher concentrations. A relatively
      higher percentage of the absorbed capsaicin could be seen in the serosal fluid as
      compared to curcumin or piperine. When these spice active principles were
      associated with mixed micelles, their in vitro intestinal absorption was
      relatively higher. Curcumin absorption in everted intestinal sac increased from
      48.7% to 56.1% when the same was present in micelles. In the case of capsaicin
      and piperine, increase in absorption was 27.8-44.4% and 43.4-57.4%, respectively,
      when they were present in micelles as compared to its native form.

PMID- 17524540
TI  - A probabilistic model for simultaneous exposure to multiple compounds from food
      and its use for risk-benefit assessment.
AB  - A model is presented which allows to quantify the simultaneous distribution of
      the exposure to two compounds, for example a health-risk and a health promoting
      compound. The model considers the total dietary intake, and can be used as a
      first step to study the effects on the balance between risks and benefits
      following changes in the consumption pattern. The exposure is modelled separately
      for intake probabilities using a betabinomial model, and for intake amounts using
      a lognormal model, and these parts are afterwards integrated by Monte Carlo
      simulation. The model is illustrated using the risk-benefit case of dioxins and
      the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA). High concentrations of both the health adverse compounds and the health
      promoting compounds are simultaneously present in fatty fish. Calculated
      exposures were compared with intake limits: the adequate intake for EPA+DHA and
      the tolerable daily intake (TDI) for dioxins. We estimate the probability that
      dioxin exposure is below TDI, the probability that EPA+DHA exposure is above the
      adequate intake, and the probability that both conditions occur simultaneously.
      We also model the dependence of these probabilities on age. In the studied
      population the exposure to both compounds is almost completely below the limits.
      A scenario study in which meat consumption was replaced by fatty fish consumption
      shows an increase in the fraction of the population with the recommended intake
      of EPA+DHA, however also the fraction of the population exceeding the TDI for
      dioxins is increased. For the example scenario the optimal amount of fatty fish
      consumption is derived.

PMID- 17524541
TI  - Five-day inhalation toxicity study of three types of synthetic amorphous silicas
      in Wistar rats and post-exposure evaluations for up to 3 months.
AB  - Evidence suggests that short-term animal exposures to synthetic amorphous silicas
      (SAS) and crystalline silica can provide comparable prediction of toxicity to
      those of 90-day studies, therefore providing the opportunity to screen these
      types of substances using short-term rather than 90-day studies. To investigate
      this hypothesis, the inhalation toxicity of three SAS, precipitated silica Zeosil
      45, silica gel Syloid 74, and pyrogenic silica Cab-O-Sil M5 was studied in Wistar
      rats. Rats were exposed nose-only to concentrations of 1, 5 or 25mg/m(3) of one
      of the SAS 6h a day for five consecutive days. Positive controls were exposed to
      25mg/m(3) crystalline silica (quartz dust), negative controls to clean air.
      Animals were necropsied the day after the last exposure or 1 or 3 months later.
      All exposures were tolerated without serious clinical effects, changes in body
      weight or food intake. Differences in the effects associated with exposure to the
      three types of SAS were limited and almost exclusively confined to the 1-day post
      exposure time point. Silicon levels in tracheobronchial lymph nodes were below
      the detection limit in all groups at all time points. Silicon was found in the
      lungs of all high concentration SAS groups 1-day post-exposure, and was cleared 3
      months later. Exposure to all three SAS at 25mg/m(3) induced elevations in
      biomarkers of cytotoxicity in bronchoalveolar lavage fluid (BALf), increases in
      lung and tracheobronchial lymph node weight and histopathological lung changes 1
      day post-exposure. Exposure to all three SAS at 5mg/m(3) induced
      histopathological changes and changes in BALf only. With all three SAS these
      effects were transient and, with the exception of slight histopathological lung
      changes at the higher exposure levels, were reversible during the 3-month
      recovery period. No adverse changes were observed in animals exposed to any of
      the SAS at 1mg/m(3). In contrast, with quartz-exposed animals the presence of
      silicon in the lungs was persistent and toxicological effects differed from those
      seen with SAS both with regard to the type and severity as well as in the time
      response profile. In quartz-exposed animals silicon in the tracheobronchial lymph
      nodes was below the detection limit but silicon was found in the lungs at
      comparable levels 0-, 1- and 3-months post-exposure. One-day post-exposure to
      quartz, elevations in biomarkers of cytotoxicity in BALf, increases in lung and
      tracheobronchial lymph node weight and histopathological lung changes were
      minimal. These effects were present at 1-month post-exposure and progressively
      more severe at 3-months post-exposure. Overall, the results of the current study
      are similar to those of other published studies that had a 90-day exposure period
      and both types of studies indicate that the lack of lung clearance is a key
      factor in the development of silicosis.

PMID- 17524542
TI  - A 13-week oral dose subchronic toxicity study of gardenia yellow containing
      geniposide in rats.
AB  - Gardenia yellow powders A, B and C, containing geniposide at 0.284%, 0.938% and
      2.783%, respectively, were administered orally to male and female SD rats as 3%
      feed admixtures for 13-weeks to evaluate any potential toxicity. Mean geniposide
      intake values were 5.72, 18.9 and 56.3mg/kg/day in groups receiving these feed
      admixtures, respectively. All animals survived the duration of the study. The
      following findings were evident in the gardenia yellow C group: chromatouria,
      slightly increased plasma total bilirubin, blackish brown discoloration of the
      kidneys and liver, brown pigments in the proximal tubular epithelium of the
      kidneys. Slightly increased plasma total bilirubin was considered to be due to
      interference of metabolite of geniposide with the system of measurement and not
      to be a toxic effect since there were no related changes in histopathology of the
      liver or in any blood chemistry parameters. Other findings were limited to
      pigmentations or discolorations attributable to metabolites of geniposide. No
      treatment-related effects were evident on body weight, food consumption,
      ophthalmology, hematology or organ weights in any group. Therefore, it was
      concluded that 3-month ingestion of the gardenia yellow powder containing
      geniposide at 2.783% (approximately 60 mg/kg/day as geniposide intake) does not
      cause any severe toxic effects.

PMID- 17524543
TI  - Cytoprotective effect of anthocyanins against doxorubicin-induced toxicity in
      H9c2 cardiomyocytes in relation to their antioxidant activities.
AB  - The effect of six anthocyanidins and seven anthocyanins against doxorubicin (Dox)
      induced cardiotoxicity in relation to their antioxidant properties was
      investigated in H9c2 cardiomyocytes. The exposure to Dox, a highly effective
      cytotoxic agent against cancer cells, induced significant cell death,
      intracellular reactive oxygen species (ROS), and lipid peroxidation in non
      tumorigenic cardiac cell culture. All anthocyanidins (50 and/or 100 microM)
      significantly increased cell survival up to 40% compared to the Dox-treated
      controls. Especially, cyanidin and delphinidin, which have an ortho-dihydroxyl
      moiety (3',4'-OH) on the flavylium skeleton, demonstrated the most potent
      protection against cytotoxicity (EC(50) of 113 and 179 microM, respectively) as
      well as lipid peroxidation induced by Dox treatment. In contrast, seven
      anthocyanins having a glycosidic moiety showed little effect in cytoprotection
      and lipid peroxidation, although they markedly blocked intracellular ROS
      generation. All anthocyanidins and anthocyanins had higher TEAC values than
      ascorbic acid, and efficaciously scavenged superoxide anion (O(2)(-)), hydrogen
      peroxide (H(2)O(2)), peroxynitrite (ONOO(-)) and nitric oxide (NO), but not
      hydroxyl radical (OH()). Their O(2)(-) scavenging activity was well correlated
      with the observed cytoprotection (r=0.67, p<0.05). These results suggest that
      anthocyanidins can ameliorate Dox-induced cardiotoxicity by, at least in part,
      scavenging of O(2)(-) generated by Dox.

PMID- 17524545
TI  - PelC is a Pseudomonas aeruginosa outer membrane lipoprotein of the OMA family of
      proteins involved in exopolysaccharide transport.
AB  - Pseudomonas aeruginosa is a gram-negative bacterium, opportunistic pathogen,
      which causes severe acute or chronic infections, as is the case with cystic
      fibrosis patients. Chronic infections are frequently accompanied by the
      development of the bacterial population into a specialized community called
      biofilm. The pelA-G gene cluster of P. aeruginosa has been shown to be involved
      in pellicle production and biofilm formation. The pel genes have been proposed to
      contribute to the formation of the exopolysaccharide-containing pellicle.
      However, the function and the subcellular localization of the seven different Pel
      proteins are poorly understood. Based on bioinformatics analysis, we have
      previously considered that PelF is a putative glycosyltransferase (GT4 family),
      whereas PelG is a Wzx-like polysaccharide transporter from the PST family. In
      this study we have further characterized the PelC protein. We have shown that
      PelC is an outer membrane lipoprotein. The N-terminal signal peptide of the PelC
      lipoprotein is sufficient to target the protein into the membranes. However, by
      constructing various PelC hybrid proteins we also proposed that efficient and
      functional outer membrane insertion of PelC requires not only the signal peptide
      and the lipid modification, but also requires the C-terminal domain of PelC.
      Because the gene encoding the outer membrane lipoprotein PelC is part of a
      putative gene cluster involved in exopolysaccharide biogenesis, we suggest that
      PelC is a new member of the outer membrane auxiliary (OMA) family of lipoprotein
      whose Wza, involved in Escherichia coli capsular polysaccharide transport, is an
      archetype.

PMID- 17524546
TI  - Aging impact on biochemical activities and gene expression of Drosophila
      melanogaster mitochondria.
AB  - The consequences of aging are characterized by a decline in the main cellular
      functions, including those of the mitochondria. Although these consequences have
      been much studied, efforts have often focused solely on a few parameters used to
      assess the "state" of mitochondrial function during aging. We performed
      comparative measurements of several parameters in young (a few days) and old (8
      and 12 weeks) adult male Drosophila melanogaster: respiratory complex activities,
      mitochondrial respiration, ATP synthesis, lipid composition of the inner
      membrane, concentrations of respiratory complex subunits, expression of genes
      (nuclear and mitochondrial) coding for mitochondrial proteins. Our results show
      that, in the mitochondria of "old" flies, the activities of three respiratory
      complexes (I, III, IV) are greatly diminished, ATP synthesis is decreased, and
      the lipid composition of the inner membrane (fatty acids, cardiolipin) is
      modified. However, the respiration rate and subunit concentrations measured by
      Western blot are unaffected. Although cellular mitochondrial DNA (mtDNA) content
      remains constant, there is a decrease in concentrations of nuclear and
      mitochondrial transcripts apparently coordinated. The expression of nuclear genes
      encoding the transcription factors TFAM, TFB1, TFB2, and DmTTF, which are
      essential for the maintenance and expression of mtDNA are also decreased. The
      decrease in nuclear and mitochondrial transcript concentrations may be one of the
      principal effects of aging on mitochondria, and could explain observed decreases
      in mitochondrial efficiency.

PMID- 17524547
TI  - The Saccharomyces cerevisiae ADP/ATP carrier-iso 1 cytochrome c fusion protein:
      one-step purification and functional analysis in vitro.
AB  - Genetic expression versus plasmidic overexpression of a functional recombinant
      fusion protein combining the yeast Saccharomyces cerevisiae mitochondrial ADP/ATP
      carrier (Anc2p) and the iso-1-cytochrome c (Cyc1p) has been investigated, with
      the main aim of increasing the polar surface of the carrier to improve its
      crystallization properties. The gene encoding the his6-tagged fusion protein was
      expressed in yeast under the control of the regulatory sequences of ScANC2 or
      under the control of the strong yeast PMA1 promoter. In both cases, the chimeric
      carrier, Anc2-Cyc1(His6)p, was able to restore growth on a non-fermentable carbon
      source of a yeast strain devoid of functional ADP/ATP carrier, demonstrating its
      transport activity. Nevertheless, when the expression vector was used, the level
      of expression of Anc2-Cyc1(His6)p was no greater than that of the chimeric
      carrier obtained in yeast mitochondria after homologous recombination. Optimal
      conditions to extract and to purify Anc2-Cyc1(His6)p were determined. A series of
      detergents was screened for their ability to extract and to preserve in vitro the
      chimeric carrier. A rapid, single step purification of Anc2-Cyc1(His6)p was
      developed, using n-dodecyl-beta-d-maltoside (DoDM) as the best detergent to
      solubilize the chimeric protein. Carboxyatractyloside- (CATR-) and nucleotide
      binding sites were preserved in the purified protein. Moreover, the Cyc1p moiety
      of Anc2-Cyc1(His6)p-CATR complex solubilized in DoDM was still able to interact
      in vitro with the cytochrome c oxidase (COX), with the same affinity as yeast
      Cyc1p. Improved production and purification of Anc2-Cyc1(His6)p-CATR complex
      opens up new possibilities for the use of this protein in crystallographic
      approaches to the yeast ADP/ATP carrier. Furthermore, Anc2-Cyc1(His6)p may be an
      useful molecular tool to investigate in vivo interactions between components of
      the respiratory chain complexes such as COX and the proteins implicated in ATP
      biogenesis, such as the ATP/ADP carrier.

PMID- 17524548
TI  - Combined flow rates of venous access devices and attachments.

PMID- 17524549
TI  - Comment on "New paradigm for prevention of cervical cancer" [Eur J Obstet Gynecol
      Reprod Biol 2007;130(1):25-9].

PMID- 17524551
TI  - Environmental aspects of the Indian Ocean Tsunami recovery.

PMID- 17524552
TI  - Implementing landscape fragmentation as an indicator in the Swiss Monitoring
      System Of Sustainable Development (Monet).
AB  - There is an increasing need and interest in including indicators of landscape
      fragmentation in monitoring systems of sustainable landscape management.
      Landscape fragmentation due to transportation infrastructure and urban
      development threatens human and environmental well-being by noise and pollution
      from traffic, reducing the size and viability of wildlife populations,
      facilitating the spread of invasive species, and impairing the scenic and
      recreational qualities of the landscape. This paper provides the rationale,
      method, and data for including landscape fragmentation in monitoring systems,
      using as an example the Swiss Monitoring System of Sustainable Development
      (Monet). We defined and compared four levels of fragmentation analysis, or
      fragmentation geometries (FGs), each based on different fragmenting elements,
      e.g., only anthropogenic, or combinations of anthropogenic and natural elements.
      As each FG has specific strengths and weaknesses, the most appropriate choice of
      FG depends on the context and objectives of a study. We present data on the
      current degree of landscape fragmentation for the five ecoregions and 26 cantons
      in Switzerland for all four FGs. Our results show that the degree of landscape
      fragmentation as quantified by the effective mesh size method is strongly
      supported by the postulates and indicator selection criteria of Monet, and we
      identify the most suitable FG focusing on the land area below 2,100 m (e.g.,
      excluding lakes) and allowing for an equitable comparison of fragmentation
      degrees among regions that differ in area covered by lakes and high mountains.
      For a more detailed analysis of landscape fragmentation in the context of
      environmental impact assessments and strategic environmental assessments, a
      combination of all four FGs may provide a more informative tool than any single
      FG.

PMID- 17524553
TI  - Strategic environmental assessment in China: motivations, politics, and
      effectiveness.
AB  - This paper examines how strategic environmental assessment has been practiced at
      the national level in China through 2005 and why it has been practiced in the
      manner observed. Based on literature reviews and interviews carried out in 2005
      and 2006, we find that bureaucratic politics between environmental and
      nonenvironmental ministries has limited the legislation and implementation of
      strategic environmental assessment to environmental assessment (EA) for a set of
      government plans defined in the 2003 Environmental Impact Assessment Law.
      Interviewees from environmental and nonenvironmental ministries and key research
      institutes have reported that few planning EAs have been performed at the
      sectoral level. Nonenvironmental ministries have either evaded the 2003
      Environmental Impact Assessment Law and have not undertaken required planning EA
      or have organized planning EA on their own without participation by the State
      Environmental Protection Administration. The rising tension between the
      environmental and nonenvironmental ministries has limited the role of planning EA
      as a participatory decision-making tool. In addition to bureaucratic politics, we
      find that weak public participation and underemphasis on social analysis in
      planning EA may have further compromised the utility of planning EA.

PMID- 17524554
TI  - A quantitative comparison between electrocoagulation and chemical coagulation for
      boron removal from boron-containing solution.
AB  - This paper provides a quantitative comparison of electrocoagulation and chemical
      coagulation approaches based on boron removal. Electrocoagulation process
      delivers the coagulant in situ as the sacrificial anode corrodes, due to a fixed
      current density, while the simultaneous evolution of hydrogen at the cathode
      allows for pollutant removal by flotation. By comparison, conventional chemical
      coagulation typically adds a salt of the coagulant, with settling providing the
      primary pollutant removal path. Chemical coagulation was carried out via jar
      tests using aluminum chloride. Comparison was done with the same amount of
      coagulant between electrocoagulation and chemical coagulation processes. Boron
      removal obtained was higher with electrocoagulation process. In addition, it was
      seen that chemical coagulation has any effect for boron removal from boron
      containing solution. At optimum conditions (e.g. pH 8.0 and aluminum dose of 7.45
      g/L), boron removal efficiencies for electrocoagulation and chemical coagulation
      were 94.0% and 24.0%, respectively.

PMID- 17524555
TI  - Photochemical degradation of 1,3-dichloro-2-propanol aqueous solutions.
AB  - The photochemical oxidation of 1,3-dichloro-2-propanol (1,3-DCP) was studied by
      following the target compound degradation, the total carbon removal rate by a
      total organic carbon (TOC) analyzer and by identifying the oxidation products by
      gas chromatography-mass spectrometry (GC-MS). The reaction was performed in a
      batch recycle reactor, at room temperature, using UV radiation provided by a low
      pressure 12W Hg lamp and H(2)O(2) as oxidant. Chloride ions, formic, acetic and
      chloroacetic acid were measured by ion chromatography. Apart from the chloride
      ions and the organic acids, the presence of 1,3-dichloro-2-propanone and
      chloroacetyl chloride was also detected and a possible pathway is proposed for
      the degradation of the parent compound. Complete degradation of 1,3-dichloro-2
      propanol was achieved and the TOC removal reached as much as 80% at the end of
      the reaction time. The effect of the initial concentration of hydrogen peroxide
      was investigated and it was established that higher concentrations of H(2)O(2)
      slow down the reaction rate. Finally, the effect of the initial concentration of
      1,3-DCP was investigated.

PMID- 17524556
TI  - Abatement of phenolic mixtures by catalytic wet oxidation enhanced by Fenton's
      pretreatment: effect of H2O2 dosage and temperature.
AB  - Catalytic wet oxidation (CWO) of a phenolic mixture containing phenol, o-cresol
      and p-cresol (500mg/L on each pollutant) has been carried out using a commercial
      activated carbon (AC) as catalyst, placed in a continuous three-phase reactor.
      Total pressure was 16 bar and temperature was 127 degrees C. Pollutant
      conversion, mineralization, intermediate distribution, and toxicity were measured
      at the reactor outlet. Under these conditions no detoxification of the inlet
      effluent was found even at the highest catalyst weight (W) to liquid flow rate
      (Q(L)) ratio used. On the other hand, some Fenton Runs (FR) have been carried out
      in a batch way using the same phenolic aqueous mixture previously cited. The
      concentration of Fe(2+) was set to 10mg/L. The influence of the H(2)O(2) amount
      (between 10 and 100% of the stoichiometric dose) and temperature (30, 50, and 70
      degrees C) on phenols conversion, mineralization, and detoxification have been
      analyzed. Phenols conversion was near unity at low hydrogen peroxide dosage but
      mineralization and detoxification achieved an asymptotic value at each
      temperature conditions. The integration of Fenton reagent as pretreatment of the
      CWO process remarkably improves the efficiency of the CWO reactor and allows to
      obtain detoxified effluents at mild temperature conditions and relatively low
      W/Q(L) values. For a given phenolic mixture a temperature range of 30-50 degrees
      C in the Fenton pretreatment with a H(2)O(2) dosage between 20 and 40% of the
      stoichiometric amount required can be proposed.

PMID- 17524557
TI  - Alkydic resin wastewaters treatment by fenton and photo-Fenton processes.
AB  - Advanced oxidation processes are an emerging option to treatment of the painting
      industry effluents. The aim of this study was to compare the effectiveness of the
      Fenton and photo-Fenton processes in chemical oxygen demand (COD), total organic
      carbon (TOC) and phenolic compounds removal from wastewaters generated during
      alkydic resins manufacture. The optimized treatment conditions are the following:
      pH 3.0, 15.15x10(-3)molL(-1) FeSO(4) and 0.30molL(-1) H(2)O(2) for a reaction
      time of 6h. photo-Fenton experiments were carried out in the presence of sunlight
      or artificial radiation and complementary additions of H(2)O(2) were made for all
      experiments. The best results were obtained with photo-Fenton process assisted
      with solar radiation, with reductions of 99.5 and 99.1% of COD and TOC levels,
      respectively. Fenton and photo-Fenton (with artificial irradiation) processes
      presented lower but not insignificant removals, within 60-80% reduction for both
      COD and TOC. In addition, an excellent removal (95%) of total phenols was
      obtained using photo-Fenton process assisted with artificial irradiation. This
      study demonstrated that the use of photo-Fenton process on alkydic resins
      wastewater treatment is very promising especially when solar light is used.

PMID- 17524558
TI  - Chronic itch and chronic pain: Analogous mechanisms.

PMID- 17524559
TI  - Ivermectin (3.15%) long-acting formulations in cattle: absorption pattern and
      pharmacokinetic considerations.
AB  - Ivermectin (IVM) is a broad-spectrum antiparasitic drug extensively used in
      veterinary medicine. The composition of the pharmaceutical preparation affects
      IVM absorption and its systemic availability. After the introduction of the first
      approved IVM formulation (propylene glycol/glycerol formal 60:40) used at 200
      microg/kg, different pharmaceutical modifications have been assayed to extend IVM
      persistent endectocide activity. Recently, IVM 3.15% long-acting (IVM-LA)
      preparations to be administered at 630 microg/kg to cattle were introduced into
      the veterinary pharmaceutical market. The work reported here was designed to
      evaluate the comparative IVM absorption pattern and plasma concentration profiles
      obtained after subcutaneous administration of the classic pioneer IVM formulation
      (1%) and two different commercially available IVM-LA preparations (3.15%) to
      cattle. Twenty-eight Holstein heifers were divided in four experimental groups
      (n=7) and treated subcutaneously as follows--Group A: IVM 1% given at 200
      microg/kg, Group B: IVM 1% administered at 630 microg/kg, Group C: IVM-LA (A)
      injected at 630 microg/kg and Group D: IVM-LA (B) given at 630 microg/kg. Blood
      samples were taken between 0.5 and 90 days post-treatment and IVM plasma
      concentrations were determined by HPLC with fluorescence detection. There were no
      differences in the persistence of IVM plasma concentrations after the
      administration of IVM 1% formulation at the two used dose levels (200 and 630
      microg/kg). Higher peak plasma concentration (C(max)) and shorter mean residence
      time (MRT) were obtained for IVM 1% given at 630 microg/kg (Group B) compared to
      the treatments with both IVM-LA preparations. The IVM-LA (A) formulation showed a
      more extended absorption process than IVM-LA (B) preparation, which accounted for
      a longer persistence of detectable IVM plasma concentrations. The parasitological
      implications of the observed differences in peak plasma concentrations (C(max)
      values) and in the IVM concentration levels measured from day 20, and afterwards
      until day 90 post-treatment, between the different preparations assayed need to
      be elucidated. The characterization of the absorption patterns and kinetic
      behaviour obtained after injection of these novel long-acting formulations used
      at three times the therapeutic dose recommended for the classic IVM preparation
      in cattle is a further contribution to the field.

PMID- 17524561
TI  - "Shift to right flypaper technique" a refined method for postage stamp
      autografting preparation.
AB  - "Lack of donor skin" is a challenge condition for autografting in the treatment
      of extensive burns. The modified Meek technique seems to be a practical solution
      for this problem. However, the equipment and consumed materials for the modified
      Meek technique are expensive which limits routine use. Designing a less
      expensive, efficient and easy to apply expansion method may improve burn care
      quality and shorten hospital stay period. Our previous study reported the
      "flypaper technique" for preparation of postage stamp autografting. The time for
      confluence of the burned wound depends on the size of the skin islands and
      expansion ratio. In clinical practice, 5mm skin squares is the preferred size of
      the skin islands; however, the positioning procedure can be modified to improve
      the wound healing process. According to the chessboard diagram, the "shift to
      right" positioning technique shortens the 10% biggest distance in six times
      expansion diagrams and 20% biggest distance in nine times expansion diagrams. By
      using a quick cutting plate, chessboard tray and petrolatum gauze, the skin
      islands can be uniformly located and correctly oriented on the gauze. This method
      allows a true expansion ratio up to nine times. In comparison with the modified
      Meek technique, this method also offers rapid wound reepithilization but with
      lower cost. However, the burn scar needs further rehabilitation and compression
      therapy to improve the functional and cosmetic result. This "shift to right
      flypaper technique" is worthy of consideration in dealing with extensive burns.

PMID- 17524560
TI  - A cell model system to study regulation of phosphotidylinositol 3-kinase and
      protein kinase B activity by cytokines/growth factors produced by type I collagen
      stimulated immune cells from patients with systemic sclerosis.
AB  - We have reported that posttranslational modification of systemic sclerosis
      patients' platelet phosphoinositide 1,3,4,5 kinase (PI 3-K) and protein kinase B
      (Akt) altered their enzymatic activities. In the present investigation, we have
      established a cell line model to study further the effects of posttranslational
      modification and modification by cytokines or growth factors of these two
      enzymes. Results from these studies suggest that posttranslational modification
      by phosphorylation of Akt and nitrotyrosylation of PI 3-K increases enzymatic
      activities, as was observed from SSc patients' platelets. These two signaling
      components are controlled by a different mechanism, which alters platelet
      reactivity towards the matrix components of vascular walls. We have used a
      megakaryotic cell line to study these two enzymes in the presence of cultured
      supernatants from peripheral blood mononuclear cells (PBMC), which were isolated
      from blood of SSc patients compared to controls including culture medium,
      rheumatoid arthritis, systemic lupus erythematosus, and osteoarthritis. The
      effect of the supernatants from SSc CI-stimulated PBMC cultures on both PI 3-K
      and Akt is specific.

PMID- 17524562
TI  - Xenoderm dressing in the treatment of second degree burns.
AB  - BACKGROUND: In many countries the standard treatment of second degree burns
      includes the use of local antibacterial agents, frequent debridement of the
      wound, and frequent dressing changes, which are debilitating and costly. Since
      accurate information about alternative cures is scanty, this study was conducted
      to assess the outcome of the use of xenoderm biologic dressings as one
      alternative. MATERIALS AND METHODS: This descriptive, goal-oriented sampling
      study was performed on 97 subjects suffering from deep partial thickness burns.
      Additionally, some of them had superficial and third degree burns. The patients
      underwent surgical operation and xenoderm dressings. The outcome of xenoderm
      application was considered such as frequency of dressings, hospital stay, the
      duration of analgesia use, wound infection, and the formation of granulation and
      scars at the burns site. RESULTS: The results of this study indicate that the
      mean hospital stay from the time the patients were referred to the emergency ward
      was 6.45+/-5.51 days and it was 4.69+/-5.51 days from the time the operation was
      performed. The mean frequency of dressings in the interval between the use of
      xenoderm and the patients' discharge was 1.51+/-1.60 times. 22.9% (22 patients)
      of the patients did not take any analgesic after the operation. 27.1% of the
      patients had superficial infection at the burns site. Granulation tissue was
      observed in 46.9% of the patients. CONCLUSION: The finding of the present study
      suggest that the use of xenoderm reduces the frequency of the dressings, Hospital
      stay, pain and analgesic. Therefore, the use of xenoderm in the treatment of
      second degree burns is recommended.

PMID- 17524563
TI  - Glucocorticoid modulation of atrial natriuretic peptide, oxytocin, vasopressin
      and Fos expression in response to osmotic, angiotensinergic and cholinergic
      stimulation.
AB  - The regulation of fluid and electrolyte homeostasis involves the participation of
      several neuropeptides and hormones that utilize hypothalamic cholinergic, alpha
      adrenergic and angiotensinergic neurotransmitters and pathways. Additionally, it
      has been suggested that hypothalamus-pituitary-adrenal axis activity modulates
      hormonal responses to blood volume expansion. In the present study, we evaluated
      the effect of dexamethasone on atrial natriuretic peptide (ANP), oxytocin (OT)
      and vasopressin (AVP) responses to i.c.v. microinjections of 0.15 M and 0.30 M
      NaCl, angiotensin-II (ANG-II) and carbachol. We also evaluated the Fos protein
      immunoreactivity in the median preoptic (MnPO), paraventricular (PVN) and
      supraoptic (SON) nuclei. Male Wistar rats received an i.p. injection of
      dexamethasone (1 mg/kg) or vehicle (0.15 M NaCl) 2 h before the i.c.v.
      microinjections. Blood samples for plasma ANP, OT, AVP and corticosterone
      determinations were collected at 5 and 20 min after stimulus. Another set of rats
      was perfused 120 min after stimulation. A significant increase in plasma ANP, OT,
      AVP and corticosterone levels was observed at 5 and 20 min after each central
      stimulation compared with isotonic saline-injected group. Pre-treatment with
      dexamethasone decreased plasma corticosterone and OT levels, with no changes in
      the AVP secretion. On the other hand, dexamethasone induced a significant
      increase in plasma ANP levels. A significant increase in the number of Fos
      immunoreactive neurons was observed in the MnPO, PVN and SON after i.c.v.
      stimulations. Pre-treatment with dexamethasone induced a significant decrease in
      Fos immunoreactivity in these nuclei compared with the vehicle. These results
      indicate that central osmotic, cholinergic, and angiotensinergic stimuli activate
      MnPO, PVN and SON, with a subsequent OT, AVP, and ANP release. The present data
      also suggest that these responses are modulated by glucocorticoids.

PMID- 17524564
TI  - Callosal responses of fast-rhythmic-bursting neurons during slow oscillation in
      cats.
AB  - The cortically generated slow oscillation consists of long-lasting
      hyperpolarizations associated with depth-positive electroencephalogram (EEG)
      waves and neuronal depolarizations accompanied by firing during the depth
      negative EEG waves. It has previously been shown that, during the prolonged
      hyperpolarizations, the transfer of information from prethalamic pathways to
      neocortex is impaired, whereas the intracortical dialogue is maintained. To study
      some of the factors that may account for the maintenance of the intracortical
      information transfer during the hyperpolarization, intracellular recordings from
      association areas 5 and 7 were performed in anesthetized cats, and the synaptic
      responsiveness of fast-rhythmic-bursting, regular-spiking and fast-spiking
      neurons was tested using single pulses to the homotopic sites in the
      contralateral areas. During the long-lasting hyperpolarizations callosal volleys
      elicited in fast-rhythmic-bursting neurons, but not in regular-spiking or fast
      spiking neurons, large-amplitude excitatory post-synaptic potentials crowned by
      single action potentials or spike clusters. Our data show that callosal volleys
      excite and lead to spiking in fast-rhythmic-bursting neurons during prolonged
      hyperpolarizations, thus enabling them to transmit information within
      intracortical networks during slow-wave sleep.

PMID- 17524566
TI  - Relationships among self-report assessments of craving in binge-drinking
      university students.
AB  - To assess the relationships among self-report craving questionnaires, and between
      craving and alcohol consumption, we administered four previously published
      measures of craving (Alcohol Urge Questionnaire, Obsessive-Compulsive Drinking
      Scale, Penn Alcohol Craving Scale, Temptation-Restraint Inventory), five single
      item Visual Analog Scales (need, urge, craving, desire, compulsion), and measures
      of alcohol consumption and drinking consequences to 112 university students
      attending a large, public state university who reported at least two binge
      drinking episodes (5+ drinks in a row by men; 4+ drinks in a row by women) in the
      previous 30 days. The associations among the multi-item self-report measures of
      craving were often larger for men than women, but the coefficients were typically
      statistically significant and meaningful regardless of gender, indicating good
      convergent validity despite differences in phrasing of items, response formats,
      and time periods over which craving was assessed. Generally smaller correlations
      among the VAS items indicated that these five terms were not inter-changeable
      among themselves (nor were they inter-changeable with scores on the multi-item
      questionnaires). Similarly to investigations using clinical samples, regression
      analyses revealed that recent drinking by binge-drinking students was associated
      with certain measures of self-reported craving.

PMID- 17524565
TI  - Functional recovery in rats with ischemic paraplegia after spinal grafting of
      human spinal stem cells.
AB  - Transient spinal cord ischemia in humans can lead to the development of permanent
      paraplegia with prominent spasticity and rigidity. Histopathological analyses of
      spinal cords in animals with ischemic spastic paraplegia show a selective loss of
      small inhibitory interneurons in previously ischemic segments but with a
      continuing presence of ventral alpha-motoneurons and descending cortico-spinal
      and rubro-spinal projections. The aim of the present study was to examine the
      effect of human spinal stem cells (hSSCs) implanted spinally in rats with fully
      developed ischemic paraplegia on the recovery of motor function and corresponding
      changes in motor evoked potentials. In addition the optimal time frame for cell
      grafting after ischemia and the optimal dosing of grafted cells were also
      studied. Spinal cord ischemia was induced for 10 min using aortic occlusion and
      systemic hypotension. In the functional recovery study, hSSCs (10,000-30,000
      cells/0.5 mul/injection) were grafted into spinal central gray matter of L2-L5
      segments at 21 days after ischemia. Animals were immunosuppressed with Prograf (1
      mg/kg or 3 mg/kg) for the duration of the study. After cell grafting the recovery
      of motor function was assessed periodically using the Basso, Beattie and
      Bresnahan (BBB) scoring system and correlated with the recovery of motor evoked
      potentials. At predetermined times after grafting (2-12 weeks), animals were
      perfusion-fixed and the survival, and maturation of implanted cells were analyzed
      using antibodies recognizing human-specific antigens: nuclear protein (hNUMA),
      neural cell adhesion molecule (hMOC), neuron-specific enolase (hNSE) and
      synapthophysin (hSYN) as well as the non-human specific antibodies TUJ1, GFAP,
      GABA, GAD65 and GLYT2. After cell grafting a time-dependent improvement in motor
      function and suppression of spasticity and rigidity was seen and this improvement
      correlated with the recovery of motor evoked potentials. Immunohistochemical
      analysis of grafted lumbar segments at 8 and 12 weeks after grafting revealed
      intense hNSE immunoreactivity, an extensive axo-dendritic outgrowth as well as
      rostrocaudal and dorsoventral migration of implanted hNUMA-positive cells. An
      intense hSYN immunoreactivity was identified within the grafts and in the
      vicinity of persisting alpha-motoneurons. On average, 64% of hSYN terminals were
      GAD65 immunoreactive which corresponded to GABA immunoreactivity identified in 40
      45% of hNUMA-positive grafted cells. The most robust survival of grafted cells
      was seen when cells were grafted 21 days after ischemia. As defined by cell
      survival and laminar distribution, the optimal dose of injected cells was 10,000
      30,000 cells per injection. These data indicate that spinal grafting of hSSCs can
      represent an effective therapy for patients with spinal ischemic paraplegia.

PMID- 17524567
TI  - Use of yttrium-90 microspheres in the treatment of unresectable hepatic
      metastases from breast cancer.
AB  - PURPOSE: Therapy for patients with unresectable liver metastases from breast
      cancer that were refractory to multiple treatment regimens was performed using
      radioactive microspheres. High doses of radiation were delivered to tumors from
      these permanently implanted yttrium-90 ((90)Y) microspheres, delivered through
      the hepatic arterial vessels. METHODS AND MATERIALS: Women from three
      institutions were selected for treatment, after screening that demonstrated
      vascular access to all tumors and after imaging confirmed that microspheres would
      be implanted only in the liver tumors. All patients were followed with laboratory
      and imaging studies at regular intervals until death. Toxicities, both acute and
      late were recorded, and actuarial survival determined. RESULTS: A total of 44
      women were treated from April 2002 to April 2005. Median follow-up of these women
      was 14 months (1-42 months). No treatment-related procedure deaths or radiation
      related veno-occlusive liver failures were found. Computed tomographic imaging
      partial response was 47% and positron emission tomographic response 95%.
      CONCLUSION: In this group of heavily pretreated patients, radioactive
      microspheres produced an encouraging median survival, with acceptable toxicity
      and a significant objective response rate, suggesting that further investigation
      of this approach is warranted.

PMID- 17524568
TI  - Proton beam therapy for aged patients with hepatocellular carcinoma.
AB  - PURPOSE: To investigate the safety and efficacy of proton beam therapy for aged
      patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Twenty-one
      patients aged > or =80 years with HCC underwent proton beam therapy. At the time
      of irradiation, patient age ranged from 80 to 85 years (median, 81 years).
      Hepatic tumors were solitary in 17 patients and multiple in 4. Tumor size ranged
      from 10 to 135 mm (median, 40 mm) in maximum diameter. Ten, 5, and 6 patients
      received proton beam irradiation with total doses of 60 Gy in 10 fractions, 66 Gy
      in 22 fractions, and 70 Gy in 35 fractions, respectively, according to tumor
      location. RESULTS: All irradiated tumors were controlled during the follow-up
      period of 6-49 months (median, 16 months). Five patients showed new hepatic
      tumors outside the irradiated volume, 2-13 months after treatment, and 1 of them
      also had lung metastasis. The local progression-free and disease-free rates were
      100% and 72% at 3 years, respectively. Of 21 patients, 7 died 6-49 months after
      treatment; 2 patients each died of trauma and old age, and 1 patient each died of
      HCC, pneumonia, and arrhythmia. The 3-year overall, cause-specific, and disease
      free survival rates were 62%, 88%, and 51%, respectively. No therapy-related
      toxicity of Grade > or = 3 but thrombocytopenia in 2 patients was observed.
      CONCLUSIONS: Proton beam therapy seems to be tolerable, effective, and safe for
      aged patients with HCC. It may contribute to prolonged survival due to tumor
      control.

PMID- 17524569
TI  - Hepatitis B virus reactivation after three-dimensional conformal radiotherapy in
      patients with hepatitis B virus-related hepatocellular carcinoma.
AB  - PURPOSE: To investigate whether three-dimensional conformal radiotherapy (3D-CRT)
      influences hepatitis B virus (HBV) reactivation and chronic hepatitis B (CHB)
      exacerbation in patients with HBV-related hepatocellular carcinoma (HCC). METHODS
      AND MATERIALS: Of the 48 HCC patients with HBV who underwent 3D-CRT to the liver,
      16 underwent lamivudine therapy before and during 3D-CRT (Group 1) and 32 did not
      receive antiviral therapy before 3D-CRT (Group 2). To analyze spontaneous HBV
      reactivation, we included a control group of 43 HCC patients who did not receive
      any specific treatment for HCC or CHB. RESULTS: The cumulative rate of radiation
      induced liver disease for Groups 1 and 2 was 12.5% (2 of 16) and 21.8% (7 of 32),
      respectively (p > 0.05). The cumulative rate of HBV reactivation was
      significantly greater in Group 2 (21.8%, 7 of 32) than in Group 1 (0%, 0/16) or
      the control group (2.3%, 1 of 43; p < 0.05 each). The cumulative rate of CHB
      exacerbation, however, did not differ significantly between Groups 2 (12.5%, 4 of
      32) and 1 (0%, 0 of 16) or the control group (2.3%, 1 of 43; p > 0.05 each). The
      CHB exacerbations in the 4 Group 2 patients had radiation-induced liver disease
      features but were differentiated by serum HBV DNA changes. Two of these patients
      required antiviral therapy and effectively recovered with lamivudine therapy.
      CONCLUSIONS: In patients with HBV-related HCC undergoing 3D-CRT, HBV reactivation
      and consequent CHB exacerbation should be considered in the differential
      diagnosis of radiation-induced liver disease, and antiviral therapy might be
      considered for the prevention of liver function deterioration after RT.

PMID- 17524570
TI  - Preoperative therapy for lower rectal cancer and modifications in distance from
      anal sphincter.
AB  - PURPOSE: To assess the frequency and magnitude of changes in lower rectal cancer
      resulting from preoperative therapy and its impact on sphincter-saving surgery.
      Preoperative therapy can increase the rate of preserving surgery by shrinking the
      tumor and enhancing its distance from the anal sphincter. However, reliable data
      concerning these modifications are not yet available in published reports.
      METHODS AND MATERIALS: A total of 98 cases of locally advanced cancer of the
      lower rectum (90 Stage uT3-T4N0-N+ and 8 uT2N+M0) that had undergone preoperative
      therapy were studied by endorectal ultrasonography. The maximal size of the tumor
      and its distance from the anal sphincter were measured in millimeters before and
      after preoperative therapy. Surgery was performed 6-8 weeks after therapy, and
      the histopathologic margins were compared with the endorectal ultrasound data.
      RESULTS: Of the 90 cases, 82.5% showed tumor downsizing, varying from one-third
      to two-thirds or more of the original tumor mass. The distance between the tumor
      and the anal sphincter increased in 60.2% of cases. The median increase was 0.73
      cm (range, 0.2-2.5). Downsizing was not always associated with an increase in
      distance. Preserving surgery was performed in 60.6% of cases. It was possible in
      nearly 30% of patients in whom the cancer had reached the anal sphincter before
      the preoperative therapy. The distal margin was tumor free in these cases.
      CONCLUSION: The results of our study have shown that in very low rectal cancer,
      preoperative therapy causes tumor downsizing in >80% of cases and in more than
      one-half enhances the distance between the tumor and anal sphincter. These
      modifications affect the primary surgical options, facilitating or making
      sphincter-saving surgery possible.

PMID- 17524571
TI  - Fat necrosis after partial-breast irradiation with brachytherapy or electron
      irradiation versus standard whole-breast radiotherapy--4-year results of a
      randomized trial.
AB  - PURPOSE: To examine the incidence and clinical relevance of fat necrosis after
      accelerated partial-breast irradiation (PBI) using interstitial high-dose-rate
      brachytherapy (HDR-BT) in comparison with partial-breast electron irradiation
      (ELE) and whole-breast irradiation (WBI). METHODS AND MATERIALS: Between 1998 and
      2004, 258 early-stage breast cancer patients were randomized to receive 50 Gy WBI
      (n = 130) or PBI (n = 128). The latter consisted of either 7 x 5.2 Gy HDR-BT (n =
      88) or 50 Gy ELE (n = 40). The incidence of fat necrosis, its impact on cosmetic
      outcome, accompanying radiologic features, and clinical symptoms were evaluated.
      RESULTS: The 4-year actuarial rate of fat necrosis was 31.1% for all patients,
      and 31.9%, 36.5%, and 17.7% after WBI, HDR-BT and ELE, respectively (p(WBI/HDR
      BT) = 0.26; p(WBI/ELE) = 0.11; p(ELE/HDR-BT) = 0.025). The respective rate of
      asymptomatic fat necrosis was 20.2%, 25.3%, and 10% of patients. The incidence of
      symptomatic fat necrosis was not significantly different after WBI (8.5%), HDR-BT
      (11.4%), and ELE (7.5%). Symptomatic fat necrosis was significantly associated
      with a worse cosmetic outcome, whereas asymptomatic fat necrosis was not. Fat
      necrosis was detectable with mammography and/or ultrasound in each case.
      Additional imaging examinations were required in 21% of cases and aspiration
      cytology in 42%. CONCLUSIONS: Asymptomatic fat necrosis is a common adverse event
      of breast-conserving therapy, having no significant clinical relevance in the
      majority of the cases. The incidence of both symptomatic and asymptomatic fat
      necrosis is similar after conventional WBI and accelerated partial-breast HDR-BT.

PMID- 17524572
TI  - [Circadian chronophysiology of the scalp].
AB  - Biological rhythms are numerous and vary according to periodicity and amplitude.
      Variations over the course of a day, particularly circadian rhythms have been
      reported in the skin of the face and forearms. However, little information is
      available about daily biorhythms of the scalp. The aim of the present study was
      to explore the chronophysiology of the scalp. We report a series of diurnal
      rhythms in 8 Caucasian men using the plexogram method at 4-h intervals over a 5
      day period. Statistically significant biorhythms were found for the colour,
      hydration, barrier function and pH of the skin, and for the sebum excretion as
      well. The early afternoon was the time of maximum increase in redness, hydration,
      pH and sebum output, combined with decreased skin barrier function. The amplitude
      of some of these biorhythms was so discrete that their clinical relevance
      remained uncertain even when they appeared statistically significant. In view of
      the apparent synchronization between them, it is likely that a central oscillator
      exerts a major influence. However, only rare subjects exhibited biorhythms for
      all the considered physiological parameters. Hence, peripheral reactivity and/or
      environmental synchronizers also play an important role to define the good and
      bad respondors to the potential biorhythms of each individual parameter.

PMID- 17524573
TI  - Genotypic analysis of Salmonella enterica serovar Typhi collected during two
      successive autumnal typhoid outbreaks in southeast Tunisia.
AB  - OBJECTIVE: Investigation of two successive autumnal outbreaks of typhoid fever
      that occurred in southeast Tunisia. PATIENTS AND METHODS: Salmonella typhi
      isolates collected from confirmed cases of typhoid fever during the two outbreaks
      occurred in autumn 2004 and 2005 and from healthy carriers were analyzed by
      antibiogram and pulsed-field gel electrophoresis (PFGE). RESULTS: A total of 86
      isolates of Salmonella enterica serovar Typhi (76 from blood culture or stool of
      patients involved in both outbreaks and 10 from stool of healthy carriers) were
      obtained. All isolates of S. typhi were fully sensitive to all antibiotics
      tested, particularly to co-trimoxazole and ciprofloxacin. All isolates of 2004
      (39 from patients and 10 from healthy carriers) appeared to be genetically
      identical when digested with SpeI, AvrII and XbaI. XbaI digestion of 2005
      outbreak isolates gave five different patterns with predominance of the 2004
      outbreak pattern. Both outbreaks were concomitant with the season of "legmi",
      fermented juice traditionally extracted from palm-tree. CONCLUSION: PFGE with
      XbaI was discriminatory and can be useful for epidemiological routine
      investigation of typhoid fever. Typing results suggests the monoclonality of 2004
      outbreak and the multiclonality of the 2005 outbreak. The epidemic clone of S.
      typhi is able to persist for long period in a quiet state in the population and
      to give again a new outbreak, when the conditions become favorable.

PMID- 17524574
TI  - A randomized controlled trial of intensive referral to 12-step self-help groups:
      one-year outcomes.
AB  - OBJECTIVE: This study implemented and evaluated procedures to help clinicians
      make effective referrals to 12-step self-help groups (SHGs). METHODS: In this
      randomized controlled trial, individuals with substance use disorders (SUDs)
      entering a new outpatient treatment episode (N=345; 96% had previous SUD
      treatment) were randomly assigned to a standard referral or an intensive referral
      to-self-help condition and provided self-reports of 12-step group attendance and
      involvement and substance use at baseline and at six-month and one-year follow
      ups (93%). In standard referral, patients received a schedule for local 12-step
      SHG meetings and were encouraged to attend. Intensive referral had the key
      elements of counselors linking patients to 12-step volunteers and using 12-step
      journals to check on meeting attendance. RESULTS: Compared with patients who
      received standard referral, patients who received intensive referral were more
      likely to attend and be involved with 12-step groups during both the first and
      second six-month follow-up periods, and improved more on alcohol and drug use
      outcomes over the year. Specifically, during both follow-up periods, patients in
      intensive referral were more likely to attend at least one meeting per week (70%
      versus 61%, p=.049) and had higher SHG involvement (mean=4.9 versus 3.7, p=.021)
      and abstinence rates (51% versus 41%, p=.048). Twelve-step involvement mediated
      the association between referral condition and alcohol and drug outcomes, and was
      associated with better outcomes above and beyond group attendance. CONCLUSIONS:
      The intensive referral intervention was associated with improved 12-step group
      attendance and involvement and substance use outcomes. To most benefit patients,
      SUD treatment providers should focus 12-step referral procedures on encouraging
      broad 12-step group involvement, such as reading 12-step literature, doing
      service at meetings, and gaining self-identity as a SHG member.

PMID- 17524575
TI  - Dietary specific antibodies in spray-dried immune plasma prevent enterotoxigenic
      Escherichia coli F4 (ETEC) post weaning diarrhoea in piglets.
AB  - In order to establish the mechanism of spray dried plasma powder (SDPP) in
      improving pig health and performance, a diet containing either 8% SDPP, spray
      dried immune plasma powder (SDIPP), or control protein (soybean and whey) ration
      was fed to piglets in an experimental model of enterotoxigenic Escherichia coli
      F4 (ETEC) post-weaning diarrhoea (PWD). SDIPP was obtained from pigs immunized
      with a vaccine containing ETEC fimbrial subunit F4 and heat-labile toxin (LT),
      and SDPP from non-immunized controls. Average daily growth (ADG) was determined,
      and daily samples of rectal faeces were assessed for diarrhoea (as percentage of
      dry matter), and ETEC excretion (in CFU/g). SDPP and SDIPP significantly (p<0.05)
      reduced diarrhoea, and SDIPP significantly reduced ETEC excretion. ADG was not
      significantly (p>0.05) affected. After the experiment, 30% of piglets tested F4
      receptor positive (F4R+). A significant correlation between F4R status and
      morbidity was found. In F4R+ animals, SDIPP significantly improved diarrhoea and
      ADG, and decreased ETEC excretion, and SDPP significantly improved diarrhoea and
      ADG. Surprisingly, SDPP reduced diarrhoea in F4R+ animals without significant
      reduction of ETEC excretion, which is most likely related to the presence of anti
      LT antibodies in SDPP. The results show that oral protection against ETEC by SDPP
      is attributable to spontaneous antibodies, in this case anti-LT antibodies.
      Furthermore, the results indicate that the combination of anti-LT and anti-F4
      antibodies as in SDIPP is most effective in ETEC prevention. Finally, the F4R
      distribution in the herd should be taken into account to correctly assess
      efficacy.

PMID- 17524576
TI  - Low pathogenicity H5N2 avian influenza outbreak in Japan during the 2005-2006.
AB  - At the end of May 2005, a low-pathogenicity avian influenza (LPAI) virus of
      subtype H5N2 was isolated for the first time from chickens in Japan. Through
      active and epidemiological surveillance, 5.78 million chickens on 41 farms were
      found to be affected and 16 H5N2 viruses were isolated. Antigenic analysis
      revealed antigenic similarity of these isolates. Phylogenetic analysis showed
      that they originated from a common ancestor and clustered with the H5N2 strains
      prevalent in Central America that have been circulating since 1994. Experimental
      infection of chickens with the index isolate (A/chicken/Ibaraki/1/05)
      demonstrated that this virus replicated efficiently in the respiratory tract
      without clinical signs, and dust-borne and/or droplet-borne transmission was
      considered as a possible mode of transmission. These results suggested that the
      H5N2 LPAI viruses isolated in Japan were highly adapted to chickens.

PMID- 17524577
TI  - Impact of Salmonella Typhimurium DT104 virulence factors invC and sseD on the
      onset, clinical course, colonization patterns and immune response of porcine
      salmonellosis.
AB  - The present study was conducted to study the impact of the virulence factors invC
      and sseD of the two type III secretion systems of Salmonella enterica serovar
      Typhimurium (S. Typhimurium) on the pathogenesis of the porcine S. Typhimurium
      DT104 infection. For this purpose, two S. Typhimurium mutant strains with a
      disrupted invC gene of the Salmonella pathogenicity island 1 or with a disrupted
      sseD gene of the Salmonella pathogenicity island 2 have been studied in
      experimental infection of pigs. Twenty-two 7-week-old male hybrid pigs were
      either infected with one of the mutants or the wild-type S. Typhimurium DT104
      strain. Each group was examined for clinical signs, Salmonella shedding rate and
      the specific antibody response. Survival and replication were evaluated by
      qualitative and quantitative determination of the colonization rate. The humoral
      and cellular immune responses were examined using isotype-specific ELISA and
      quantitative real-time PCR of IL-2, IL-4, IL-10, IL-12 and IFN-gamma. The results
      proved that both mutants had a lower virulence (with marked differences between
      both mutants) than the wild-type and that both virulence factors have importance
      in porcine salmonellosis. Only pigs infected with the wild-type S. Typhimurium
      DT104 exhibited typical clinical symptoms of salmonellosis like anorexia,
      vomiting, disturbed demeanour, fever and diarrhoea. Deletion of the invC gene
      resulted in a significantly reduced colonization rate. Interestingly, the mRNA
      expression of both type-1 and type-2 cytokines were significantly decreased in
      pigs infected with either the invC-mutant and the sseD-mutant strain.

PMID- 17524578
TI  - Crystal growth formation in melt extrudates.
AB  - The purpose of the study was to investigate the physical state of hot-melt
      extruded guaifenesin tablets containing either Acryl-EZE or Eudragit L100-55 and
      to study the physicochemical factors influencing crystal growth of guaifenesin on
      the surface of the extrudates. The powder mixtures containing Acryl-EZE were
      extruded on a single-screw Randcastle Microtruder at 20rpm and at temperatures of
      90, 95, 110 degrees C (zones 1, 2, 3, respectively) and 115 degrees C (die),
      before being manually cut into tablets (250+/-5mg). Extrudates containing
      Eudragit L100-55, TEC and guaifenesin were extruded at temperatures ranging from
      60 to 115 degrees C. Modulated differential calorimetry (DSC) was used to
      demonstrate the plasticizing effect of guaifenesin on Eudragit L100-55. Powder X
      ray diffraction (PXRD) showed that while the drug powder is crystalline,
      extrudates containing up to 25% drug exhibited an amorphous diffraction profile.
      Extrudates containing higher drug concentrations showed an amorphous profile with
      some crystalline peaks corresponding to guaifenesin, indicating that the limit of
      solubility of drug in the matrix had been exceeded. Scanning electron microscopy
      was used to demonstrate that drug crystallization was a surface phenomenon and
      dependent on the drug concentration. In vitro dissolution testing showed no
      effect of surface crystallization of guaifenesin on drug release rates of
      extruded matrix tablets. The influence of hydrophilic polymeric additives
      including PVP K25, polycarbophil, PEG 3,350, poloxamer 188 or poly(ethylene
      oxide) as crystal growth inhibitors was investigated at a level of 10% based on
      the drug content. The extent of crystal growth was reduced for all additives.
      Complete drug release in pH 6.8 phosphate buffer was prolonged from 4h in
      extrudates containing Acryl-EZE and guaifenesin to 8h in extrudates containing
      Eudragit L100-55, TEC and guaifenesin. Drug release in extrudates containing
      Eudragit L100-55 and guaifenesin was not affected by the presence of hydrophilic
      additives present at 10% based on the drug content. In vitro drug release studies
      showed no significant change during storage for up to 6 months at 25 degrees
      C/60% relative humidity and 40 degrees C/75% relative humidity.

PMID- 17524579
TI  - Capacity and tolerance of a new device for ocular drug delivery.
AB  - A new method to increase the drug-capacity of the OphthaCoil, a flexible and
      tubular device for delivery of drugs to the tear film of the eye, was explored.
      Poly(2-hydroxyethyl methacrylate)- and poly(2-hydroxyethyl methacrylate-co-1
      vinyl-2-pyrrolidone)-microspheres were prepared by suspension polymerization. The
      resultant particles were swollen in a highly concentrated solution of either the
      dye fluorescein sodium or the antibiotic chloramphenicol. The loaded particles
      were placed in the central cavity of the ocular device. In vitro release profiles
      showed a six-fold increase of the capacity for the dye fluorescein sodium, but
      not for the antibiotic chloramphenicol. Flexibility measurements revealed that by
      introducing microspheres in the central cavity of the device, flexibility did not
      decrease. Finally, a preliminary in vivo evaluation of the device (n=5) was done
      for a 2h-period to assess the tolerance of the device in the human eye.
      Ophthalmologic examinations and photographs of the eye indicated no signs of
      irritation. Volunteers reported that the presence of the device in the eye could
      be noticed, but no irritation was reported.

PMID- 17524581
TI  - Agreement and meaning: rethinking consensus analysis.
AB  - This study provides a critical perspective on "informant agreement (consensus)
      analysis" as it is used in ethnobotany and ethnopharmacology. It recasts the
      concept at a higher cultural level, and it describes the cultural agreement about
      reported medicinal plant use for the native peoples of North America. It examines
      some plant use categories around which there is significant cross cultural
      agreement, and some categories which lack such agreement. The study then proposes
      a theoretical approach to understanding the efficacy of plants lacking
      significant consensus in their usage. The study considers the implications of
      this second form of efficacy defined here as the "meaning response", but often
      referred to as the "placebo effect".

PMID- 17524580
TI  - Immunomodulation of RAW264.7 macrophages by GLIS, a proteopolysaccharide from
      Ganoderma lucidum.
AB  - The immunomodulatory effect of Ganoderma lucidum immunomodulating substance
      (GLIS) on macrophages has been investigated as part of on-going research into the
      anti-cancer properties of Ganoderma lucidum. Proliferation of bone marrow
      macrophages (BMMs) was enhanced by GLIS in a dose-dependent manner. Microscopic
      examination revealed that numerous GLIS-treated RAW264.7 macrophages were
      enlarged and formed pseudopodia. Exposure of RAW264.7 macrophages to GLIS
      resulted in significant increases in NO production, induction of cellular
      respiratory burst activity, and increased levels of IL-1beta, IL-12p35 and IL
      12p40 gene expression. Our data indicate that GLIS activates the immune system by
      modulating cytokine production.

PMID- 17524582
TI  - Age estimation using carpals: study of a Slovenian sample to test Cameriere's
      method.
AB  - Carpals are often used as age indicators. In a recent study, Cameriere et al.
      studied the use of the ratio between the total area of carpal bones and epiphyses
      of the ulna and radius (Bo) and carpals (Ca) as age indicators. The present
      study, of a sample of 158 Slovenian children and adolescents aged between 6 and
      16 years, focused on analysing the best regression for age estimation. The
      regression model yielded the following equation: age=-3.411+0.942
      g+20.927(Bo/Ca), and explained 91.6% of total variance (R(2)=0.916). The median
      of the absolute values of residuals (observed age minus predicted age) was 0.09
      years, with a quartile deviation of 0.786 years, and a standard error of estimate
      of 0.658 years. Comparisons between the previous equation referring to Slovenian
      children and the equivalent linear equation proposed by Cameriere et al. did not
      reveal any significant differences between the intercepts and slopes of the two
      linear models. These results suggested a common regression model for both Italian
      and Slovenian samples. The common regression model, describing age as a linear
      function of gender and Bo/Ca ratio, yielded the following linear regression
      formula: age=-2.907+0.408 g+20.757(Bo/Ca). This model explained 86% of total
      variance (R(2)=0.86). The median of the absolute values of residuals (observed
      age minus predicted age) was 0.02 years, with a quartile deviation of 1.02 years
      and a standard error of estimate of 0.96 years.

PMID- 17524583
TI  - A nine year old girl with thyrotoxicosis, ataxia, and chorea.
AB  - Neurologic manifestations are common in patients with thyroid disease. We
      describe the case of a nine year old girl with Graves disease and the unique
      combination of chorea and ataxia that both resolved after treatment of
      hyperthyroidism.

PMID- 17524584
TI  - [Depressive disorders and use of health services in the French population
      according to the Health Barometer 2005].
AB  - BACKGROUND: Whereas depressive disorders are major problems of public health,
      there is few reliable data in general population in France. OBJECTIVE: The
      objective of this study is to estimate the 12-month prevalence rates of
      depressive disorders and use of health services in French general population, and
      to identify the sociodemographic variables associated with Major Depressive
      Episode (MDE) and use of health services for mental disorder. METHOD: This study
      was carried out from the data of the Health Barometer 2005, a random survey about
      several topics of health. Thirty thousand five hundred and fourteen individuals
      from 12 to 75 years were interviewed by telephone from October 2004 to February
      2005. Depressive disorders were assessed by a standardized tool (CIDIsf)
      according to the classification of the DSM-IV (16710 individuals have answered
      the questions of mental health: 60% of the individuals aged 15 or older).
      RESULTS: 7.8% of the individuals interviewed reported a MDE over the last 12
      months. In majority, the episodes were relatively serious (0.4% of mild episode
      and 2.9% of single episode) and were mainly associated with sex, age and marital
      status. Among these individuals, only 38.3% had consulted a health service for
      mental health during that period and 10.8% had psychotherapy. The main associated
      factors for use of services were age, educational level and depression severity.
      CONCLUSION: These first national reliable dataset confirms the extent of
      depressive disorders in general population and highlights the problems of use of
      health services and treatments. Also, this study shows that there are instruments
      and methodologies making it possible to study mental disorders and use of health
      services in general population. It suggests to look further into the exploration
      of these issue and to develop this kind of survey to study other problems of
      mental health.

PMID- 17524585
TI  - Image-guided radiofrequency ablation (RFA) of spinal tumors.
AB  - PURPOSE: To evaluate retrospectively the efficacy and safety of radiofrequency
      ablation (RFA) in patients with spinal tumors. MATERIALS AND METHODS: Forty-one
      patients (25 men, 16 women; age range, 46-82 years) with nonresectable primary or
      secondary tumor involvement of the spine unresponsive to chemo- and radiotherapy
      received RFA treatment. Two radiofrequency ablation systems, one with a cool-tip
      electrode and one with an expandable electrode catheter, were used. Both systems
      work impedance controlled with a power output of 150- 200 W. Each coagulation
      cycle lasted 12-15 min depending on tumor impedance. Several single RFA cycles of
      15 min each were used for overlapping RFAs in tumors with diameters of more than
      3 cm. Temperature was kept between 50 degrees C and 120 degrees C and was chosen
      according to spinal cord distance and patient heat tolerance during the ablation.
      Multi-slice computed tomography (CT) combined with C-arm fluoroscopy guided the
      intervention. Efficacy outcomes were assessed after about 6 weeks, 6 months, and
      more than 6 months using standardized questionnaires and indices regarding tumor
      pain, pain disability, functional activities, quality of life, neurological
      status, and tumor progression. RESULTS: RFA significantly reduced tumor-induced
      pain within 6 weeks, improved daily activities, and maintained quality of life.
      Mean time to tumor progression was 730+/-54 days (Kaplan-Meier estimate). No RFA
      associated complications were reported. CONCLUSION: RFA of primary and secondary
      spinal tumors, which were unresponsive to chemo- and radiotherapy and prone to
      progression, is a safe, resource-saving, and highly effective percutaneous
      technique in patients with nonresectable spinal tumors.

PMID- 17524586
TI  - Sonoelastography of the prostate: comparison with systematic biopsy findings in
      492 patients.
AB  - OBJECTIVE: The aim of this study was to assess the value of sonoelastography (SE)
      for prostate cancer detection in comparison with systematic biopsy findings.
      MATERIAL AND METHODS: Four hundred and ninety two PSA screening volunteers (mean
      age: 61.9+/-8.6) with an total PSA >1.25 ng/mL and a free to total PSA ration of
      <18% underwent SE of the prostate before 10 core systematic prostate biopsy.
      Tissue elasticity of the peripheral zone was investigated only. Tissue elasticity
      was displayed from red (soft) to green (intermediate) and to blue (hard). Only
      hard lesions (blue) were considered to be suspicious for prostate cancer. The
      peripheral zone of the prostate was divided in 3 regions on each side: base, mid
      gland, apex. A different investigator performed systematic biopsy, and the biopsy
      findings were compared with the SE findings. RESULTS: In 125 of 492 patients
      (25.4%) systematic biopsy demonstrated prostate cancer. Cancer was detected in
      321 of 2952 (11%) outer gland areas (74 in the base, 106 in the mid-gland, 141 in
      the apex). The Gleason score ranged from 3 to 10 (mean: 6.5). In SE 533 of 2952
      (18.1%) suspicious areas were detected and 258 of these areas (48.4%) showed
      cancer. Most of the false-positive findings (275/533 areas; 51.6%) were
      associated with chronic inflammation and atrophy especially at the basal prostate
      areas. The sensitivity by entire organ was calculated with 86% and the
      specificity 72%. The analysis by outer gland areas showed the highest sensitivity
      in the apex (79%). The specificity by outer gland areas ranged between 85% and
      93%. The correlation between SE findings and biopsy results was high (p<0.001).
      CONCLUSION: Sonoelastography findings showed a good correlation with the
      systematic biopsy results. The best sensitivity and specificity was found in the
      apex region. Sonoelastography seems to offer a new approach for differentiation
      of tissue stiffness of the prostate and may therefore improve prostate cancer
      detection.

PMID- 17524587
TI  - Small hyperintense hepatic lesions on T1-weighted images in patients with
      cirrhosis: evaluation with serial MRI and imaging features for clinical
      benignity.
AB  - PURPOSE: The aim of this study was to evaluate the frequency and magnetic
      resonance imaging (MRI) features of clinically benign, small (<2 cm) hyperintense
      hepatic lesions in the cirrhotic liver on T1-weighted MR images seen at serial
      MRI. MATERIALS AND METHODS: This study included 189 patients with cirrhosis, who
      underwent hepatic MRI more than twice with an interval of at least 12 months. The
      initial MR images were reviewed for the presence of small hyperintense lesions on
      T1-weighted images. The size, location and signal intensity on T2-weighted images
      as well as enhancement patterns of the corresponding lesions were recorded.
      RESULTS: On the initial T1-weighted MR images, 43 small hyperintense hepatic
      lesions were detected in 23 (12%) of 189 patients. Twelve (28%) of 43 lesions
      showed early enhancement and were pathologically diagnosed as hepatocellular
      carcinoma (HCC) during the follow-up period. Thirty-one (72%) of 43 lesions
      showed no early enhancement with various signal intensity on T2-weighted images
      (hyperintensity=4, isointensity=20, hypointensity=7). Among these 31 lesions, 12
      showed no interval change, while 11 disappeared (n=10) or decreased in size
      (n=1). In the remaining eight lesions, seven were diagnosed as HCC on the basis
      of pathologic confirmation or the interval growth. CONCLUSION: Small hyperintense
      hepatic lesions on T1-weighted magnetic resonance (MR) images without early
      enhancement on the arterial-phase contrast-enhanced dynamic studies in patients
      with cirrhosis usually showed no interval growth or disappeared during the serial
      MRI. These lesions with additional findings of iso- or hypointensity on the T2
      weighted MR images without "washout effect" on the contrast-enhanced equilibrium
      phase images may more frequently be clinically benign or hyperplastic nodules
      than HCCs.

PMID- 17524588
TI  - Phase-encoding strategies for optimal spatial resolution and T1 accuracy in 3D
      Look-Locker imaging.
AB  - The Look-Locker (LL) imaging method provides an accurate and efficient approach
      for mapping the spin-lattice relaxation time, T(1). However, the same recovery of
      signal during LL image acquisition required to estimate T(1) also results in
      unwanted modulation of k-space. This is particularly problematic with 3D LL
      imaging as the number of phase-encoding steps during the recovery interval (e.g.,
      16) increases in an effort to reduce imaging times. This modulation of k-space
      has the effect of introducing a point spread function (PSF), which can lead to
      either image blurring (if the earlier tip angles are assigned to the centre of k
      space) or edge enhancement (if the earlier tip angles are assigned to the edges
      of k-space), thus corrupting T(1) estimation, particularly for small objects. In
      this study, the PSF and its effect on the acquired images for four different
      interleaved phase-encode schemes (centric-in, centric-out, sequential and hybrid
      sequential) are simulated for a range of T(1), tip angle and 3D LL acquisition
      parameters expected in practice. It is shown by simulation and confirmed
      experimentally in phantoms that a hybrid sequential phase-encoding scheme reduces
      image blurring while maintaining T(1) accuracy ( approximately 2%) and precision
      (2%) over a range of object sizes down to 2 pixels (2 mm).

PMID- 17524589
TI  - Identification of activated regions during a language task.
AB  - Functional magnetic resonance imaging (fMRI) techniques are based on the
      assumption that changes in neural activity are accompanied by modulation in the
      blood-oxygenation-level-dependent (BOLD) signal. In addition to conventional
      increases in BOLD signals, sustained negative BOLD signal changes are
      occasionally observed in many fMRI experiments, which show regions of cortex that
      seem to respond in antiphase with primary stimulus. The existence of this so
      called negative BOLD response (NBR) has been observed and investigated in many
      functional studies. Several theoretical mechanisms have been proposed to account
      for it, but its origin has never been fully explained. In this study, the
      variability of fMRI activation, including the sources of the negative BOLD
      signal, during phonological and semantic language tasks, was investigated in six
      right-handed healthy subjects. We found significant activations in the brain
      regions, mainly in the left hemisphere, involved in the language stimuli
      [prominent in the inferior frontal gyrus, approximately Brodmann Areas (BA)7,
      BA44, BA45 and BA47, and in the precuneus]. Moreover, we observed activations in
      motor regions [precentral gyrus and supplementary motor area (SMA)], a result
      that suggests a specific role of these areas (particularly the SMA) in language
      processing. Functional analysis have also shown that certain brain regions,
      including the posterior cingulate cortex and the anterior cingulate cortex, have
      consistently greater activity during resting states compared to states of
      performing cognitive tasks. In our study, we observed diffuse NBR at the cortical
      level and a stronger negative response in correspondence to the main sinuses.
      These phenomena seem to be unrelated to a specific neural activity, appearing to
      be expressions of a mechanical variation in hemodynamics. We discussed about the
      importance of these responses that are anticorrelated with the stimulus. Our data
      suggest that particular care must be considered in the interpretation of fMRI
      findings, especially in the case of presurgical studies.

PMID- 17524590
TI  - Genetic improvement of Saccharomyces cerevisiae for xylose fermentation.
AB  - There is considerable interest in recent years in the bioconversion of forestry
      and agricultural residues into ethanol and value-added chemicals. High ethanol
      yields from lignocellulosic residues are dependent on efficient use of all the
      available sugars including glucose and xylose. The well-known fermentative yeast
      Saccharomyces cerevisiae is the preferred microorganism for ethanol production,
      but unfortunately, this yeast is unable to ferment xylose. Over the last 15
      years, this yeast has been the subject of various research efforts aimed at
      improving its ability to utilize xylose and ferment it to ethanol. This review
      examines the research on S. cerevisiae strains that have been genetically
      modified or adapted to ferment xylose to ethanol. The current state of these
      efforts and areas where further research is required are identified and
      discussed.

PMID- 17524591
TI  - Diffusion tensor imaging of the corpus callosum: a cross-sectional study across
      the lifespan.
AB  - Previous studies have demonstrated strong developmental trends of white matter
      using in vivo neuroimaging. However, few studies have examined white matter using
      diffusion tensor imaging across the lifespan. In the present study we examined
      fractional anisotropy and volume in the corpus callosum in four groups (children,
      adolescents, young adults, and elderly). Results revealed a curvilinear
      relationship in the analysis of the fractional anisotropy values for these four
      groups, with fractional anisotropy values increasing in childhood and
      adolescence, reaching their peak in young adulthood, followed by a non
      significant decline in the elderly. Volumetric analysis of corpus callosum
      regions revealed a similar pattern, with an increase in volume from childhood and
      adolescence through young adulthood, and a non-significant decrease in volume in
      the elderly group. These results define the microstructural development of the
      white matter across the lifespan. Future studies are required to examine the
      neurobehavioral correlates of these neuroimaging indices.

PMID- 17524592
TI  - Evaluation of dietetic students' and interns' application of a lifestyle-oriented
      nutrition-counseling model.
AB  - OBJECTIVE: To assess dietetic students' and interns' skills to effectively apply
      a lifestyle-oriented nutrition-counseling model. METHODS: Between 1999 and 2004,
      121 dietetics students and interns (82% retained) were trained to provide
      nutrition counseling and certified using a standardized patient evaluation
      format. Supervising registered dietitians and students evaluated transcripts of
      their counseling sessions using a modified version of the Dietitian's
      Interviewing Rating Scale (DIRS). Clients evaluated their counselor's skills. t
      Tests determined differences between the supervisor and student's DIRS
      evaluation, and from an acceptable score of "4". ANOVA distinguished differences
      by student academic category and client group. RESULTS: The student counselors
      scored >or=4 for five of the six skills sets, but significantly below 4 for
      "transitions" (the internal summaries between sections). The students rated
      themselves significantly higher than their supervisor did on rapport building,
      questioning skills, and approach to plan. CONCLUSION: The student counselors
      effectively applied the skills of a lifestyle-oriented nutrition-counseling
      model, and can benefit from supervisor-provided feedback. PRACTICE IMPLICATIONS:
      Nutrition counseling training/practice through various dietetic curriculums can
      provide future dietitians with the skills and the confidence they need to
      successfully assist their clients to make lifestyle behavior changes.

PMID- 17524593
TI  - Language and connectedness in the medical and psychiatric interview.
AB  - OBJECTIVE: To present and develop "connectedness" as a linguistically based
      concept for research and teaching of the medical and psychiatric interview; and
      to illustrate how this concept may be operationalized for systematic study and
      use. METHODS: We describe the concept and its theoretical background, illustrate
      it with examples, and describe a basic rating scale for connectedness that can be
      used for research and teaching purposes. RESULTS: Connectedness is grounded in
      established concepts from the linguistic field of discourse analysis and is
      applicable to the study and teaching of medical and psychiatric interviews.
      CONCLUSIONS: Connectedness is worthy of further study to enhance our
      understanding and our teaching of the interview. PRACTICE IMPLICATIONS:
      Connectedness is a concept directly applicable to teaching and practice.

PMID- 17524594
TI  - Preventing without stigmatizing: the complex stakes of information on AIDS.
AB  - OBJECTIVE: To evaluate the impact that the marking of the argumentative
      orientation and the temporal framing of the HIV incidence can have on the intent
      to adopt preventive behavior and the attitude towards the fight against AIDS.
      METHODS: We elaborated a text presented as an epidemiological information message
      about HIV/AIDS in which we varied the marking of the argumentative orientation
      (high marking versus low marking) and the framing of the HIV infection (yearly
      estimates versus daily estimates). Subjects were asked to read it carefully and
      to answer some questions about their preventive intentions and opinions as
      regards the fight against AIDS. RESULTS: The high marking of the argumentative
      orientation and the daily estimates increase the subject's preventive intentions
      but also reinforce their support for a coercive management of the epidemiological
      situation. CONCLUSION: These results are discussed within the framework of
      critical studies on mass media and studies discussing the links between
      experienced stigmata, stress and psychological distress. Some limitations of our
      study are also considered. PRACTICE IMPLICATIONS: This study could be useful for
      the designers of prevention campaigns aimed at the general public.

PMID- 17524595
TI  - Storytelling for promoting colorectal cancer prevention and early detection among
      Latinos.
AB  - OBJECTIVE: Health promotion efforts directed at Latinos may be more effective
      when culturally adapted methods are used. Our study was designed to test a novel
      communication modality for promoting colorectal cancer (CRC) prevention and
      screening messages among Latinos. METHODS: We compared a culturally aligned,
      brief storytelling educational intervention (ST) to a numeric risk tool
      intervention (NR) based on the Harvard Cancer Risk Index. Both interventions
      included risk factor information and recommendations for primary prevention and
      screening for CRC. Sixty-four Latinos (mean age 46.8, 86% female) were randomized
      and completed pre- and post-tests. RESULTS: Participants in ST indicated intent
      to add significantly more servings of vegetables (p=.030) and more minutes of
      exercise (p=.018) to daily routines than those in NR. Most respondents (ST and
      NR) reported intentions to recommend CRC screening to friends and relatives.
      CONCLUSIONS: These data provide support for storytelling's potential to promote
      health behavior change with cultural relevance for Latinos. PRACTICE
      IMPLICATIONS: Storytelling shows promise as an effective method for reaching one
      of the historically underserved ethnic groups with cancer prevention and
      screening information.

PMID- 17524596
TI  - Are Washington Circle performance measures associated with decreased criminal
      activity following treatment?
AB  - This study examines the association between adherence to during-treatment process
      measures of quality (defined as initiation and engagement in treatment as
      developed by the Washington Circle) and outcome measures (defined as arrests and
      incarcerations) in the following year. The data come from the Oklahoma Department
      of Mental Health and Substance Abuse Services administrative data system linked
      to data from state criminal justice agencies. Clients who initiated a new episode
      of outpatient treatment and who engaged in treatment were significantly less
      likely to be arrested or incarcerated in the following year. Initiation of
      substance abuse treatment alone, without engagement in treatment, was not
      significantly associated with arrests or incarcerations. These findings validate
      the clinical importance of the Washington Circle performance measures of
      initiation and engagement. Applying the "process-of-care" measures can make a
      difference when they are used as a target for quality improvement in treatment
      facilities.

PMID- 17524597
TI  - Appendiceal neoplasms and pseudomyxoma peritonei: a population based study.
AB  - BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated
      incidence of 1 per million per year, and is thought to originate usually from an
      appendiceal mucinous epithelial neoplasm. However it is not known exactly how
      often these neoplasms lead to PMP. The aim of this study is to investigate the
      incidence of both lesions and their relation. METHODS: The nationwide pathology
      database of the Netherlands (PALGA) was searched for the incidence of all
      appendectomies, the incidence of primary epithelial appendiceal lesions and the
      incidence and pathology history of patients with PMP. All regarded the 10-year
      period of 1995-2005. RESULTS: In the 10-year period 167,744 appendectomies were
      performed in the Netherlands. An appendiceal lesion was found in 1482 appendiceal
      specimens (0.9%). Nine percent of these patients developed PMP. Coincidentally,
      an additional epithelial colonic neoplasm was found in 13% of patients with an
      appendiceal epithelial lesion. A mucinous epithelial neoplasm was identified in
      0.3% (73% benign, 27% malignant) of appendiceal specimens and 20% of these
      patients developed PMP. For mucocele and non-mucinous neoplasm the association
      with PMP was only 2% and 3%, respectively. From the nationwide database 267
      patients (62 men and 205 women) with PMP were identified, which demonstrates an
      incidence of PMP in the Netherlands approaching 2 per million per year. The
      primary site was identified in 68% and dominated by the appendix (82%).
      CONCLUSIONS: Primary epithelial lesions of the appendix are rare. One third of
      these lesions are mucinous epithelial neoplasms and especially these tumours may
      progress into PMP. The incidence of PMP seems to be higher than thought before.
      Furthermore there is a considerable risk of an additional colonic epithelial
      neoplasm in patients with an epithelial neoplasm at appendectomy.

PMID- 17524598
TI  - Long-term urinary dysfunction after mesorectal excision: a prospective study with
      intraoperative electrophysiological confirmation of nerve preservation.
AB  - BACKGROUND: Bladder dysfunctions are well-recognized complications after nerve
      sparing mesorectal excision for rectal cancer. This study sought to
      symptomatically analyze the extent of recovery from major and minor urinary
      symptoms in patients with signs of bladder denervation. METHODS: Sixty-two
      patients with mesorectal excision for rectal cancer were investigated
      prospectively. Pelvic autonomic nerve preservation (PANP) was assessed
      macroscopically and with the aid of intraoperative electrical stimulation of
      pelvic autonomic nerves (INS). Bladder function was evaluated with the
      International Prostate Symptom Score (IPSS) and the Quality of life index (Qol).
      Median follow-up was 20 months (range 3-40 months). RESULTS: Forty-six patients
      with INS-confirmed preservation of parasympathetic nerves remained unchanged in
      early and long-term urinary function (IPSS: median 1; range 0-24 and Qol 0; range
      0-5). In 15 patients without confirmation of PANP (unilaterally or bilaterally)
      on INS, voiding function was significantly more impaired postoperatively (IPSS:
      median 10; range 0-25 and Qol 3; range 0-6) and at long-term follow-up (IPSS:
      median 9; range 0-25 and Qol 3; range 0-6) (p<0.001). Voiding function was
      improved in 4 of 10 patients with major and minor symptoms. In 5 of 6 patients
      with long-term bladder dysfunction INS assessed parasympathetic nerve damage
      unilaterally (3/5) and bilaterally (2/5). CONCLUSION: Long-term voiding
      disturbance after mesorectal excision was found to be a serious complication. INS
      while monitoring intravesical pressure is a valuable aid in predicting long-term
      bladder function after TME. The device may serve a secondary preventive function
      in enabling the initiation of early urologic therapy.

PMID- 17524599
TI  - [Ketamine for paediatric anaesthesia: useful, fool or...?].
AB  - The use of ketamine for paediatric sedation-anaesthesia-analgesia is still
      growing despite the availability of adequate alternatives. Based on the
      literature, the present work will briefly review the well-known properties
      underlying the widespread use of this drug in this particular clinical situation.
      In adult patients, the use of ketamine as a new element of the balanced
      anaesthesia-analgesia is also ever growing. This is based on the recently
      demonstrate antihyperalgesic and anti-pro-inflammatory properties of this drug.
      This work questions the existence of such benefits in the paediatric population.
      Finally, the "dark side" of ketamine will be discussed. Experimental studies on
      developing brain clearly demonstrate that this old anaesthetic is a potent
      trigger for pathologic neuronal apoptosis.

PMID- 17524600
TI  - [Neurobiology of the chronicisation of pain in children: the memory of pain and
      its painful memory].
AB  - Reviewing the development of nociceptive circuits provides the rationale behind
      the need to modify and reduce premature painful experiences, especially during
      the "plastic" neonatal phase. Indeed, if physiological mechanisms of the
      functional nociceptive system follow a harmonious and predetermined development,
      it is the individual personal experience, intrinsically random, which will shape
      the final reactivity of this system and the later painful experience. If pain
      would not have been the organism's alarm system, we could have simply compared it
      by analogy to other sensorial systems, which its development depends exclusively
      on the presence of environmental stimuli. The eyes wait for light, the ears for
      sound, the skin to be touched, the tongue to taste and the olfactory bulbs to
      smell. However with pain it is not the quantitative exposure that determines its
      development, but rather the context-laden aspects of its affliction which in turn
      create the complex experience and "memory" of pain. Prolonged, but also
      "unnecessary" exposure to pain transforms it into a futile sensation, which
      impacts the individual immediately but also resonates into its future. This
      article reviews recent neurobiological mechanisms (such as neural circuitry,
      neurotrophins, peripheral and central sensitization, inhibitory pathways) now
      known to develop during the chronicisation and apprenticing of pain in the
      growing individual. Its cognizance is vital for a better comprehension of adult
      pain.

PMID- 17524601
TI  - [Hepatic encephalopathy in cirrhotic patients admitted to intensive care unit:
      still a poor outcome].

PMID- 17524602
TI  - [Steroids in the critical care children with septic shock and other conditions].
AB  - Steroids are indicated in paediatric intensive care as anti-inflammatory drugs or
      for substitutive treatment. During septic shock, the incidence of adrenal
      insufficiency (AI) varies between 18 a 52%, depending on the relative or absolute
      nature of the AI. Contrary to adults, for whom long courses of low doses of
      corticosteroids were shown to reduce mortality and increased shock reversibility,
      particularly in those with a negative synacthene test, no study provided
      sufficient evidence to show a benefit of steroids in terms of outcome in children
      with septic shock. In neonates, AI occurs frequently after cardiac surgery and
      the administration of steroids can improve haemodynamic condition. The
      recommended dose of hydrocortisone during septic shock or after cardiac surgery
      is 30 to 100 mg/m(2)/d. Dexamethasone is efficient to reduce postextubation
      stridor in children and neonate and the rate of reintubations in neonate. During
      croup, oral or parenteral steroids reduce clinical symptoms. Dexamethasone also
      reduces the incidence of severe chronic lung disease and the duration of tracheal
      intubation in premature infants. However the high incidence of side effects,
      particularly on the central nervous system, makes steroids currently not
      recommended for bronchopulmonary dysplasia. At last, steroids are indicated for
      severe asthma and for bacterial meningitis. In this latter indication,
      dexamethasone was shown to improve neurological outcome, indeed mortality in
      Haemophilus influenzae and Streptococcus pneumoniae meningitis.

PMID- 17524603
TI  - [Perioperative anti-inflammatory drug use: which evidences for their utility and
      safety?].
AB  - OBJECTIVE: To bring together the most recent evidences concerning the utility and
      safety of perioperative anti-inflammatory drug use. DATA SOURCES: References were
      obtained from computerised bibliographic data banks (MeSH terms: NSAIDs, coxibs,
      steroids, surgery, anaesthesia), followed by manual search. DATA SYNTHESIS:
      NSAIDs, coxibs and steroids used alone or in association have been demonstrated
      to be effective for relieving postoperative pain. However, the benefits of
      perioperative anti-inflammatory drug use may go beyond the postoperative
      analgesia. In some cases, anti-inflammatory drugs have been shown to decrease the
      incidence of morphine side-effects, postoperative nausea and vomiting or to
      improve postoperative recovery. Nevertheless, NSAIDs have been found to be a risk
      factor of severe postoperative bleeding requiring surgical haemostasis after some
      surgical procedures. In contrast, coxibs have been shown to promote arterial
      thrombosis after others surgical procedures.

PMID- 17524604
TI  - [Pharmacokinetics of tramadol in children].
AB  - The recent studies focusing on the pharmacokinetics of tramadol in children
      contributed to the increase popularity of tramadol as an analgesic alternative in
      clinical practice. Tramadol is a racemic mixture of 2 enantiomers that have
      comparable pharmacokinetic profile and this lack of difference is also observed
      with their main active metabolite, O-demethyl tramadol (M1). The serum
      concentrations of this metabolite depend largely on the activity of the
      cytochrome P450 and particularly of the enzyme CYP2D6 which reaches its maturity
      in the newborn. Nevertheless, the interindividual variability observed in the
      pharmacokinetics of tramadol and consequently in the pharmacodynamic profile is
      mainly due to the genetic polymorphism of cytochrome P450.

PMID- 17524605
TI  - [Pulmonary arterial hypertension in children: new therapeutic approaches].
AB  - Pulmonary arterial hypertension (PAH) contributes significantly to the morbidity
      and mortality of diverse cardiopulmonary disorders in paediatrics. The treatment
      of PAH has dramatically changed over the last decade. A better understanding of
      the pathophysiological mechanisms has lead to the introduction of several new
      therapies both in the field of idiopathic and familial PAH or PAH associated with
      underlying conditions (i.e. congenital heart disease, connective tissue disease,
      HIV) as well as in the field of acute PAH. The endothelial dysfunction,
      considered a one of the striking problems of this disease, is characterized by a
      decreased production of vasodilatory-antiproliferative substances (prostacyclins,
      nitric oxide) and increased production of vasoconstrictive-proliferative
      substances (endothelin, thromboxanes). It is currently possible to try to
      palliate to these deficits by administering prostacyclins or nitric oxide, as
      well as antagonizing the effect of endothelin through endothelin receptor
      antagonists. These progresses have first appeared in the adult population but
      have been rapidly applied to the paediatric population. This short review will
      discuss these new therapeutic approaches and refers to several large reviews
      recently published for a more comprehensive description.

PMID- 17524606
TI  - [Delayed tamponade and traumatic myocardial contusion: evaluate the risk after
      blunt chest trauma].
AB  - Cardiac contusion is frequently found in patients with blunt chest trauma. It is
      important to note that even if there is a low incidence of pericardial effusion,
      iterative echocardiography should be used to provide essential information for
      the diagnosis of cardiac tamponade which can be life-threatening during
      hospitalisation. The case has been reported of a 17-year-old patient with blunt
      thoracic trauma in whom the introduction of anticoagulant treatment induced a
      delayed cardiac tamponade with myocardiac failure 3 weeks after a cardiac
      contusion. Thoracic computed tomography confirmed the diagnosis and moreover,
      revealed a pleural effusion with pulmonary embolism. The drainage of the
      pericardial effusion (700 ml) rapidly restored haemodynamic stability and as such
      has been proved to be life-saving.

PMID- 17524607
TI  - [Clinical usefulness of positron emission tomography in prostate cancer].
AB  - In prostate cancer, use of FDG, the radiopharmaceutical currently most widely
      used in oncology, is limited to the most aggressive cancers and, in the absence
      of another tracer, to attempting to localise occult recurrences detected
      biochemically (elevated PSA serum levels). Four other PET tracers are currently
      suggested in various situations of prostate cancer development: for guiding
      biopsies, for diagnosis and staging of the primary cancer and of local or
      metastatic recurrences, especially in bone, and for localizing occult biochemical
      recurrence. This article is illustrated by cases summarising our experience with
      fluoromethylcholine-(18F) and PET/CT. They cover a wide spectrum of clinical
      settings: localisation of intraprostatic neoplastic lesions, initial staging,
      monitoring treatment by ultrasound, detection of occult recurrences and
      characterisation of images on conventional imaging modalities, which are
      questionable or difficult to interpret.

PMID- 17524608
TI  - [Endocrine consequences of hemochromatosis].
AB  - The two most frequent endocrine complications of hemochromatosis are diabetes
      mellitus and hypogonadotrophic hypogonadism. Other endocrine disorders related to
      this disease are very rare and are described especially in the most severe and
      earliest posttransfusion iron overloads. Endocrine complications are evidence of
      advanced hemochromatosis, often already associated with cirrhosis. Given the low
      frequency of HFE mutations in type 2 diabetes, routine genetic testing in this
      population does not seem reasonable. Testing for iron overload is recommended in
      subjects with atypical type 2 diabetes (for example, patients who are not
      overweight) and in cases of hypogonadism, characteristic pigmentation, or
      cirrhosis. Phlebotomy plays an important role in the management of endocrine
      complications of hemochromatosis, especially when diagnosis is early. In all
      cases of hypogonadotrophic hypogonadism, primary hemochromatosis must be
      considered.

PMID- 17524610
TI  - Conserved interactions of a compact highly active enhancer/promoter upstream of
      the rhodopsin kinase (GRK1) gene.
AB  - Rhodopsin kinase (RK) is a conserved component of the light adaptation and
      recovery pathways shared among rod and cone photoreceptors of a variety of
      species. To gain insight into transcriptional mechanisms driving RK and
      potentially other genes of similar spatial profile, the components and the
      interactions of the highly compact enhancer/promoter region (E/P) upstream of the
      human RK gene were examined. Cross-species comparison outlined an active 49-bp
      widely shared E/P core as the major site of conservation in the entire 5'
      flanking sequence. The area consisted of a bicoid-type homeodomain recognition
      cassette and a unique T-rich module interacting with TATA-binding proteins.
      Homeodomain interactions involved primarily Crx and secondarily Otx2. Both
      strongly stimulated the E/P. In the absence of Crx, persistent E/P activity
      shifted from the outer retina to the inner to follow the Otx2 pattern. The
      spatial patterns were largely unaffected by the absence of rod transcription
      factors, Nrl and Nr2e3, and the RK transcriptional activity preceded the surge in
      rod-specific transcription. Conserved bicoid homeodomain factors thus appear to
      be the key factors governing localization of RK E/P activity in retina and
      photoreceptors.

PMID- 17524609
TI  - Bile salts enhance bacterial co-aggregation, bacterial-intestinal epithelial cell
      adhesion, biofilm formation and antimicrobial resistance of Bacteroides fragilis.
AB  - Bacteroides fragilis is the most common anaerobic bacterium isolated from human
      intestinal tract infections. Before B. fragilis interacts with the intestinal
      epithelial cells, it is exposed to bile salts at physiological concentrations of
      0.1-1.3%. The aim of this study was to determine how pre-treatment with bile
      salts affected B. fragilis cells and their interaction with intestinal epithelial
      cells. B. fragilis NCTC9343 was treated with conjugated bile salts (BSC) or non
      conjugated bile salts (BSM). Cellular ultrastructure was assessed by electron
      microscopy, gene expression was quantified by comparative quantitative real-time
      RT-PCR. Adhesion to the HT-29 human intestinal cell line and to PVC microtitre
      plates (biofilm formation) was determined. Exposure to 0.15% BSC or BSM resulted
      in overproduction of fimbria-like appendages and outer membrane vesicles, and
      increased expression of genes encoding RND-type efflux pumps and the major outer
      membrane protein, OmpA. Bile salt-treated bacteria had increased resistance to
      structurally unrelated antimicrobial agents and showed a significant increase in
      bacterial co-aggregation, adhesion to intestinal epithelial cells and biofilm
      formation. These data suggest that bile salts could enhance intestinal
      colonization by B. fragilis via several mechanisms, and could therefore be
      significant to host-pathogen interactions.

PMID- 17524611
TI  - Phylogenetic and expression analysis of ZnF-AN1 genes in plants.
AB  - In plants, ZnF-AN1 genes are part of a multigene family with 13 members in
      Arabidopsis thaliana, 19 members in Populus trichocarpa, 17 members in Oryza
      sativa, at least 11 members in Zea mays, and 2 members in Chlamydomonas
      reinhardtii. All ZnF-AN1 genes contain the ZnF-AN1 domain. According to the
      phylogenetic analysis of the ZnF-AN1 domain, we divided plant ZnF-AN1 genes into
      two types. The coding sequences of most type I members do not possess any
      introns, while most type II members do possess intron(s). Through Northern blot
      analysis of maize members and digital Northern analysis of Arabidopsis members,
      we found that most ZnF-AN1 genes are involved in responses to abiotic stresses.
      The evolutionary analysis indicated that the expansion rate of type I was higher
      than that of type II. After expansion, some ZnF-AN1 genes may have gained new
      functions, some may have lost their functions, and some were specialized to
      perform their functions in stress-specific or tissue-specific modes. In addition,
      we propose an evolutionary model of type II ZnF-AN1 genes in plants.

PMID- 17524612
TI  - Sleep enhances serum interleukin-7 concentrations in humans.
AB  - Growing evidence points towards a beneficial effect of sleep on immune function.
      Human studies indicate that the T cell mediated adaptive immune function
      including formation of antigen specific antibodies is facilitated by sleep. Along
      this line, here we aimed to dissociate the effect of sleep and circadian rhythm
      on circulating interleukin-7 (IL-7) and interleukin-15 (IL-15). These cytokines
      play a key role in the homeostatic regulation of naive and memory T cell numbers
      and are critical for the differentiation of memory T cells. Serum IL-7
      concentration and expression of membrane-bound IL-15 (mIL-15) on CD14(+)
      monocytes were measured in 18 men on two occasions: once during a regular 24-h
      sleep-wake cycle and another time during a 24-h period of continuous wakefulness.
      During sleep and especially during late sleep serum IL-7 concentrations were
      distinctly increased as compared to wakefulness (p<0.05). mIL-15 density on
      monocytes remained unchanged by sleep. The sleep-dependent increase in IL-7
      concentration was associated with increased REM sleep, but did not correlate with
      concentrations of GH, cortisol or norepinephrine during sleep. The findings
      concur with the notion of a supportive influence of sleep on T cell function
      related to formation of T cell memory.

PMID- 17524613
TI  - Exercise-induced liver beta2-microglobulin expression is related to lower IgG
      clearance in the blood.
AB  - Voluntary wheel running exercise induced higher antigen-specific IgG in
      circulating blood is well recognized in mice. This antibody response may be
      regulated by an exercise-induced mechanism that protects against IgG catabolism.
      The recent hypothesis that the beta2-microglobulin gene is implicated in IgG
      protection is investigated further on mice voluntary wheel running. Male C57BL/6N
      mice were intraperitoneally immunized with 0.375microg/kg (body weight) of
      tetanus toxoid to induce primary and secondary antibody responses. At the peak
      concentration of blood tetanus toxoid specific IgG in this experiment, we
      administered (125)I-labeled mouse IgG. To determine how (125)I-IgG half-life is
      prolonged in voluntary wheel running exercised mice, we observed the tissue
      radioactivity (125)I-IgG. Significantly higher blood IgG concentrations were
      demonstrated in the exercised group compared to non-exercised group (P<.05). The
      mean value of radioactivity in the liver was higher in the exercised group
      (P<.05). Furthermore, extracted IgG concentration of exercised mouse liver was
      higher than that of non-exercised group (P<.05). Immunohistochemical analysis
      showed dramatically increased tissue IgG in the liver of the exercised group
      (P<.05). The gene expression of beta2-microglobulin was up-regulated in the
      exercised mouse liver (P<.05). There is a significant correlation between liver
      accumulation of (125)I-IgG and (125)I-IgG concentration in the blood (P<.05). In
      addition, there is a significant correlation between extracted total hepatic IgG
      and beta2-microglobulin in the liver (P<.05). These findings indicate that
      voluntary wheel running exercise-induced liver beta2-microglobulin expression is
      related to lower IgG clearance in the blood.

PMID- 17524615
TI  - A variational EM approach to predictive uncertainty.
AB  - In many applications of regression, the conditional average of the target
      variable is not sufficient for prediction. The dependencies between the
      explanatory variables and the target variable can be complex calling for
      modelling of the full conditional probability density. The ubiquitous problem
      with such methods is overfitting since due to the flexibility of the model the
      likelihood of any datapoint can be made arbitrarily large. In this paper a method
      for predicting uncertainty by modelling the conditional density is presented
      based on conditioning the scale parameter of the noise process on the explanatory
      variables. The model is constructed in such a manner that the unpredictability of
      the scale of the target distribution translates into a more robust predictive
      distribution. The overfitting problems are solved by learning the model using
      variational EM. The method is experimentally demonstrated with synthetic data as
      well as with real-world environmental data. The viability of the approach was put
      to test in the 'Predictive uncertainty in environmental modelling' competition
      held at WCCI'06. The proposed method won the competition.

PMID- 17524614
TI  - The effects of 40 hours of total sleep deprivation on inflammatory markers in
      healthy young adults.
AB  - Inflammatory cytokines are released in response to stress, tissue damage, and
      infection. Acutely, this response is adaptive; however, chronic elevation of
      inflammatory proteins can contribute to health problems including cardiovascular,
      endocrine, mood, and sleep disorders. Few studies have examined how sleep
      deprivation acutely affects inflammatory markers, which was the aim of the
      current study. Nineteen healthy men and women aged 28.05+/-8.56 (mean+/-SD) were
      totally sleep deprived for 40 h under constant routine conditions. Pro
      inflammatory markers: intracellular adhesion molecule-1 (ICAM-1), E-selectin,
      vascular adhesion molecule-1 (VCAM-1), c-reactive protein (CRP), interleukin-6
      (IL-6), and interleukin-1beta (IL-1beta), and the anti-inflammatory cytokine
      interleukin-1 receptor antagonist (IL-1ra) were assayed in plasma. Daytime levels
      during baseline (hours 1-15 of scheduled wakefulness) were compared to daytime
      levels during sleep deprivation (hours 25-39 of scheduled wakefulness), thus
      controlling for circadian phase within an individual. Repeated measures ANOVA
      with planned comparisons showed that 40 h of total sleep deprivation induced a
      significant increase in E-selectin, ICAM-1, IL-1beta, and IL-1ra, a significant
      decrease in CRP and IL-6, and no significant change in VCAM-1. Alterations in
      circulating levels of pro- and anti-inflammatory cytokines and cell adhesion
      molecules during sleep deprivation were consistent with both increased and
      decreased inflammation. These findings suggest that one night of sleep loss
      triggers a stress response that includes stimulation of both pro- and anti
      inflammatory proteins in the healthy young subjects tested under our experimental
      conditions.

PMID- 17524616
TI  - Nonlinear analog predictor analysis: a coupled neural network/analog model for
      climate downscaling.
AB  - Synoptic downscaling models are used in climatology to predict values of weather
      elements at one or more stations based on values of synoptic-scale atmospheric
      circulation variables. This paper presents a hybrid method for climate prediction
      and downscaling that couples an analog, i.e., k-nearest neighbor, model to an
      artificial neural network (ANN) model. In the proposed method, which is based on
      nonlinear principal predictor analysis (NLPPA), the analog model is embedded
      inside an ANN, forming its output layer. Nonlinear analog predictor analysis
      (NLAPA) is a flexible model that maintains the ability of the analog model to
      preserve inter-variable relationships and model non-normal and conditional
      variables (such as precipitation), while taking advantage of NLPPA's ability to
      define an optimal set of analog predictors that maximize predictive performance.
      Performance on both synthetic and real-world hydroclimatological benchmark tasks
      indicates that the NLAPA model is capable of outperforming other forms of analog
      models commonly used in synoptic downscaling.

PMID- 17524617
TI  - Automated detection of lung nodules in CT images using shape-based genetic
      algorithm.
AB  - A shape-based genetic algorithm template-matching (GATM) method is proposed for
      the detection of nodules with spherical elements. A spherical-oriented
      convolution-based filtering scheme is used as a pre-processing step for
      enhancement. To define the fitness function for GATM, a 3D geometric shape
      feature is calculated at each voxel and then combined into a global nodule
      intensity distribution. Lung nodule phantom images are used as reference images
      for template matching. The proposed method has been validated on a clinical
      dataset of 70 thoracic CT scans (involving 16,800 CT slices) that contains 178
      nodules as a gold standard. A total of 160 nodules were correctly detected by the
      proposed method and resulted in a detection rate of about 90%, with the number of
      false positives at approximately 14.6/scan (0.06/slice). The high-detection
      performance of the method suggested promising potential for clinical
      applications.

PMID- 17524618
TI  - Stimulation of phospholipase Cbeta by membrane interactions, interdomain
      movement, and G protein binding--how many ways can you activate an enzyme?
AB  - Signaling proteins are usually composed of one or more conserved structural
      domains. These domains are usually regulatory in nature by binding to specific
      activators or effectors, or species that regulate cellular location, etc.
      Inositol-specific mammalian phospholipase C (PLC) enzymes are multidomain
      proteins whose activities are controlled by regulators, such as G proteins, as
      well as membrane interactions. One of these domains has been found to bind
      membranes, regulators, and activate the catalytic region. The recently solved
      structure of a major region of PLC-beta2 together with the structure of PLC
      delta1 and a wealth of biochemical studies poises the system towards an
      understanding of the mechanism through which their regulations occurs.

PMID- 17524619
TI  - Anchorage value of surgical titanium screws in orthodontic tooth movement.
AB  - The aim of this study was to evaluate the clinical stability and anchorage value
      of titanium screws in orthodontic tooth movement. Nine patients, who needed
      maximum anchorage for canine retraction, were selected. Records of 10 patients
      with similar malocclusions who had received conventional treatment were used as
      controls. In the maxilla and mandible 27 mini-screws, diameter 2mm and length 9
      or 11 mm, were used. At the end of the first stage of orthodontic treatment the
      first premolar teeth were extracted after taking a lateral cephalometric
      radiograph. After 1 week, a retraction force of 180 g was applied to the canines.
      The second cephalometric X-rays were taken and evaluated after the completion of
      canine retraction (mean duration of 23.2 weeks). Results were analysed using
      Fisher Exact, Wilcoxon signed ranks and paired t-tests. Displacement of the first
      molars and screws before and after treatment showed no significant changes in
      either the vertical or horizontal plane. The first molar movements in the study
      and control groups were only significant in the antero-posterior plane in both
      maxilla and mandible. Of the 9 screws in maxilla and 18 screws in mandible, 2 and
      3 screws showed clinical failure, respectively. The failed screws were replaced
      by other screws that withstood the applied force until the end of treatment. In
      conclusion, titanium screws can be used reliably as a form of anchorage.

PMID- 17524620
TI  - Cognitive remediation therapy (CRT) for young early onset patients with
      schizophrenia: an exploratory randomized controlled trial.
AB  - BACKGROUND: Schizophrenia with an onset in adolescence is known to be associated
      with a poorer outcome and cognitive difficulties. These impairments have an
      impact on quality of life and represent treatment targets. Cognitive remediation
      therapy (CRT) attempts to improve cognitive deficits by teaching information
      processing strategies through guided mental exercises. The objective of this
      study is to evaluate the efficacy of CRT in alleviating cognitive deficits
      compared to treatment as usual and explore the mediating and moderating effects
      of cognitive improvement. METHOD: Single-blind randomized controlled trial with
      two groups, one receiving CRT (N21) and the other standard care (N19) assessed at
      baseline, 3 months (post therapy) and follow-up (3 months post therapy).
      Participants were recruited from specialist inpatient and community mental health
      services and were young patients with recent onset schizophrenia (average age of
      18) and evidence of cognitive and social behavioural difficulties. The
      intervention was individual cognitive remediation therapy delivered over a period
      of 3 months with at least three sessions per week. The main outcome measures were
      cognition (memory, cognitive flexibility and planning) and secondary outcomes
      (symptoms, social contacts and self-esteem). RESULTS: Compared to standard care,
      CRT produced significant additional improvements in cognitive flexibility as
      measured by the Wisconsin Card Sort Test (WCST). Therapy moderated the effects of
      improved planning ability on symptoms such that improvements only had a
      beneficial effect when they were achieved in the context of CRT. Improvements in
      cognition in all domains had a direct effect on social functioning and
      improvements in WCST had a direct effect on overall symptom improvement.
      CONCLUSIONS: Cognitive remediation therapy can contribute to the improvement in
      WCST even in adolescents. The changes in cognitive outcomes also contributed to
      improvements in functioning either directly or solely in the context of CRT.
      Evidence of the mediator and moderator effects of cognitive changes should lead
      to more effective therapy development.

PMID- 17524621
TI  - Mild hearing impairment and psychotic experiences in a normal aging population.
AB  - BACKGROUND: Hearing impairment (HI) in the elderly may be a risk factor for
      psychosis, but associations between HI and psychotic disorder or psychotic
      experiences have been reported more consistently in younger than in older
      populations. The aims of this study were to replicate the positive association
      between hearing impairment and psychotic experiences and to clarify any
      differences between groups of young and old individuals in a non-clinical, normal
      aging general population sample. METHODS: HI, assessed at baseline and at 3-year
      follow-up, and psychotic experiences, assessed at 3-year follow-up, were analysed
      in a group of 848 individuals aged 33 to 89 years between 1999 and 2004. HI was
      determined on the basis of both self-report and audiometric examination. The
      "psychoticism" and "paranoid ideation" subscales from the SCL-90-R were used to
      assess level of psychotic experiences. RESULTS: Self-reported hearing problems
      expressed as conversational HI (beta=0.080, 95% CI: 0.23, 7.90, p=0.038) and
      subjective HI (beta=0.087, 95%CI: 0.70, 10.30, p=0.025), but not audiometric
      objective HI, were associated with psychotic experiences. In those with hearing
      aids, associations with psychotic experiences were only present if accompanied by
      self-reported hearing problems that persisted in spite of the hearing aid. In
      addition, HI increased the risk for psychotic experiences specifically in younger
      rather than older individuals. CONCLUSIONS: Self-reported hearing problems rather
      than audiometric or remediated hearing loss may contribute to the development of
      psychotic experiences in younger rather than in older individuals.

PMID- 17524622
TI  - Neurotrophins and schizophrenia.
AB  - Neurotrophins have established roles in neuronal development, synaptogenesis, and
      response to stress/anxious stimuli. Moreover, these agents are neuromodulators of
      monoaminergic, GABAergic, and cholinergic systems. Amidst a growing appreciation
      of the developmental neurobiology of schizophrenia--as well as the propensity for
      progressive brain changes--there is emergent information on abnormalities in the
      expression of neurotrophins in schizophrenia. This article reviews the literature
      on neurotrophins and schizophrenia. A schema for understanding the neurobiology
      of relapse in schizophrenia is offered.

PMID- 17524623
TI  - Comparative analysis of megasomes in members of the Leishmania mexicana complex.
AB  - Megasomes are large lysosome-like structures, previously described in amastigote
      forms of Leishmania belonging to the mexicana complex, whose major constituents
      are the cysteine proteinases. Routine observation of thin sections of amastigotes
      obtained from species of the mexicana complex revealed variations in size and
      number of megasomes according to the species, and also between amastigotes
      obtained from axenic cultures and from infected animals. Three-dimensional
      reconstruction of amastigotes, stereology and immunocytochemical localization of
      cysteine proteinase revealed significant differences between the three Leishmania
      species examined, L. amazonensis, L. mexicana and L. pifanoi. The relative volume
      of megasomes in lesion-derived amastigotes was higher than in axenic amastigotes
      of L. amazonensis and L. mexicana. The relative volume of megasomes from lesion
      derived amastigotes of L. mexicana was 2-3 times higher than in L. amazonensis.
      Axenic amastigotes of L. pifanoi showed a small relative volume of megasomes and
      low cysteine proteinase activity, and were not able to produce lesions in the
      animals, whereas axenic amastigotes of L. mexicana and L. amazonensis did. There
      were significant differences in the structural organization, distribution within
      the cell, size and number of megasomes, and in the characteristics of cysteine
      proteinases found in the amastigotes of the three Leishmania species. These
      results suggest that these organelles and their constituents may be involved in
      the infectivity and virulence of Leishmania species.

PMID- 17524624
TI  - Antibiotic and heavy metal resistance in motile aeromonads and pseudomonads from
      rainbow trout (Oncorhynchus mykiss) farms in Australia.
AB  - A total of 129 Pseudomonas spp. and 90 Aeromonas spp. were isolated from nine
      rainbow trout (Oncorhynchus mykiss) farms in Australia. All the isolates were
      tested for sensitivity to 15 antibiotics and the multiresistant strains were
      tested for sensitivity to seven heavy metals. Minimal inhibitory concentrations
      (MICs) were determined by the agar dilution method. In Pseudomonas spp.,
      resistance to amoxicillin, cefalothin, ceftiofur, ticarcillin, chloramphenicol,
      florfenicol, streptomycin, nitrofurantoin and trimethoprim was widespread,
      whereas resistance to cefotaxime and oxolinic acid was less common and only
      single isolates were resistant to tetracycline and sulfamethoxazole; all isolates
      were sensitive to ciprofloxacin and gentamicin. In Aeromonas spp., resistance to
      amoxicillin and cefalothin was widespread, resistance to ticarcillin,
      tetracycline and streptomycin was common, whilst resistance to ceftiofur,
      florfenicol and sulfamethoxazole was less common. Single isolates were resistant
      to chloramphenicol, nitrofurantoin and trimethoprim, and all isolates were
      sensitive to cefotaxime, oxolinic acid, ciprofloxacin and gentamicin. Multiple
      resistance was also observed. Most isolates were tolerant to different
      concentrations of various heavy metals, as evidenced by their MICs ranging from
      6.25 microg/mL to >3200 microg/mL. These results confirm our previous findings
      that bacteria resistant to antibiotics are present in fish and sediments from
      aquaculture in Australia. In addition, we have found resistance to heavy metals
      in fish and sediment isolates. Much of the antibiotic resistance detected is
      likely to be intrinsic, although resistance to oxytetracycline, streptomycin and
      sulfonamides suggests either contamination from run-off from farms or perhaps off
      label use of antibiotics in a situation where no antibiotics are licensed for use
      in aquaculture.

PMID- 17524625
TI  - Recent advances in antifungal chemotherapy.
AB  - For over 50 years, amphotericin B deoxycholate (AmBD) has been the 'gold
      standard' in antifungal chemotherapy, despite its frequent toxicities. However,
      improved treatment options for invasive fungal infections (IFIs) have been
      developed during the last 15 years. Newer antifungal agents, including less toxic
      lipid preparations of AmBD, triazoles and the echinocandins, have been added to
      our armamentarium against IFIs. Some of these newer drugs can now replace AmBD as
      primary therapy (e.g. caspofungin for candidiasis, voriconazole for
      aspergillosis), whilst others offer new therapeutic options for difficult-to
      treat IFIs (e.g. posaconazole for zygomycosis, fusariosis and
      chromoblastomycosis). It is interesting that extended use of newer antifungals
      such as fluconazole, despite decreasing the mortality attributed to candidiasis,
      resulted in selection of species resistant to several antifungals (Candida
      krusei, Candida glabrata); whilst several publications suggest that prolonged use
      of voriconazole may expose severely immunocompromised patients to the risk of
      zygomycosis (breakthrough). On the other hand, the differences in the mode of
      action of newer antifungals such as echinocandins raise the question whether
      combination antifungal therapy is more effective than monotherapy. Finally, the
      availability of an oral formulation with excellent biosafety of several newer
      antifungals (e.g. posaconazole) makes them candidates for prophylactic or
      prolonged maintenance therapy.

PMID- 17524626
TI  - Clinical evaluation of negative symptoms in schizophrenia.
AB  - The florid positive symptoms of schizophrenia (hallucinations, delusions, grossly
      disordered thinking) are often obvious. By comparison, negative symptoms
      (flattened affect, impoverished speech, apathy, avolition, anhedonia) are subtler
      and more difficult to recognize and diagnose. However, there is increasing
      recognition of the importance of negative symptoms in patients with
      schizophrenia. Secondary negative symptoms attributable to such factors as
      unrelieved positive symptoms, the adverse effects of antipsychotic
      pharmacotherapy, or social isolation may subside with resolution of such factors.
      In contrast, primary negative symptoms are an intrinsic aspect of schizophrenia;
      they are persistent and have been associated with poorer clinical outcomes.
      Although the lack of a reliably effective treatment for negative symptoms is a
      serious unmet need in this patient population, accurate diagnosis is still
      important. Assessment of suspected negative symptoms, using validated rating
      scales, can help to rule out comorbid affective or cognitive disorders that may
      mimic negative symptoms and to distinguish primary negative symptoms from
      potentially reversible secondary negative symptoms. This article reviews the
      definitions and classification of negative symptoms, compares the tools available
      for their assessment, and offers practical clinical algorithms for sorting
      through the differential diagnosis.

PMID- 17524627
TI  - No ecological effect modification of the association between negative life
      experiences and later psychopathology in adolescence: A longitudinal community
      study in adolescents.
AB  - BACKGROUND: The aim of the study was to examine the potential contribution of
      exposure to bullying and adverse life events to the development of
      psychopathology in adolescents, and possible effect modification by neighbourhood
      social capital. METHODS: Two waves of routine, longitudinal, standard health
      examinations at local community paediatric health services, pertaining to 749
      adolescents living in Maastricht (The Netherlands) who were attending second
      grade of secondary school (age 13/14 years) and approximately 2 years later going
      to the fourth grade (age 15/16 years), were analysed. A self-report questionnaire
      was used, including measures of psychopathology and two measures of negative life
      experiences, exposure to bullying and adverse life events, that were available
      for both age groups and subjected to (multilevel) regression analysis. RESULTS:
      Exposure to bullying in the past school-year as well as the experience of adverse
      life events over a 12 month period, at the age of 13/14 years, predicted an
      increase in psychopathology at follow-up. Exposure to bullying was associated
      with the development of hyperactivity and emotional problems, while the
      experience of adverse life events predicted the development of conduct problems.
      Family-related adverse events had greatest effect sizes. Effects of bullying and
      adverse life events were not moderated by neighbourhood social capital.
      CONCLUSION: Negative life experiences impact on liability to psychopathology in
      adolescents independent of the wider social environment.

PMID- 17524628
TI  - Reduced cerebral glucose metabolism in patients at risk for Alzheimer's disease.
AB  - While significantly reduced glucose metabolism in fronto-temporo-parietal and
      cingulate cortices has been demonstrated in Alzheimer's disease (AD) compared
      with controls, cerebral glucose metabolism in patients with mild cognitive
      impairment who subsequently develop AD is less well-defined. In the present study
      we measured cerebral glucose metabolism by positron emission tomography (PET)
      with (18)F-2-fluoro-2-deoxy-D-glucose in 14 patients with aging-associated
      cognitive decline (AACD), 44 patients with AD, and 14 healthy control subjects at
      baseline. The AACD patients were clinically followed up, and conversion to AD was
      determined. Compared with controls, AACD patients had significantly reduced
      glucose metabolism in the right precuneus, posterior cingulate, right angular
      gyrus, and bilateral middle temporal cortices, while the respective deficits were
      more pronounced in AD patients and also involved the frontal cortices. AACD
      patients who subsequently converted to AD (AACD-converters) showed more extended
      metabolic changes which also involved the frontal and temporal cortices, right
      cingulate gyrus, right thalamus, and bilateral precuneus.

PMID- 17524629
TI  - [Blackwater fever in children during cerebral malaria: 3 case reports in Bamako].
AB  - BACKGROUND: Blackwater fever is a rare but serious form of malaria in children.
      Diagnosis relies on clinical symptoms and on the color of the urines. OBJECTIVES:
      To describe blackwater fever in children, a disease whose prevalence seems to be
      increasing. METHOD: We report 3 cases of blackwater fever observed in our
      institution. RESULTS: In 2 cases, acute renal insufficiency with oligoanuria was
      observed. In all the 3 cases, treatment with quinine was stopped and replaced by
      injectable artemether. Evolution was dependent on renal function, and included in
      1 patient neurological sequels consisting in aphasia. CONCLUSION: Blackwater
      fever is a severe affection whose diagnosis should be evoked using the color of
      urine. Evolution is usually favorable in the pediatric population, when adequate
      care can be provided.

PMID- 17524630
TI  - [Fusobacterium necrophorum meningitis: forgotten complication of a gingivitis].
AB  - By now Lemierre's syndrome is a seldom-described disease whose prognosis depends
      on the precocity of treatment. CASE PRESENTATION: We report the case of an 11
      month-old child, with a fulminant Fusobacterium necrophorum meningitis, which
      derived from a gingival infection, with fatal outcome. CONCLUSION: This atypical
      case of Lemierre's syndrome (young age occurrence and localisation) underlines
      the potential severity of F. necrophorum sepsis.

PMID- 17524631
TI  - Description of a mirror-image doublet from a Brazilian strain of Gastrostyla
      setifera (Engelmann, 1862) Kent, 1882 (Ciliophora: Stichotrichia).
AB  - The present work describes a mirror-image doublet morph found in a Brazilian
      strain of the stichotrich ciliate Gastrostyla setifera (Engelmann, 1862) Kent,
      1882, obtained from a sample of water and sediment from an urban freshwater
      stream in the city of Juiz de Fora (Minas Gerais, Brazil). The doublet measured
      63 x 49 microm, and had two components where the right one has upside-down
      arranged adoral membranelles with a set of small oblique membranelles at its
      proximal (posterior) end. The fronto-ventral-transverse ciliature comprised 34
      cirri, mostly related to the left component, as well as two marginal rows. On the
      dorsal surface there were eight dorsal kineties and six caudal cirri.
      Dorsomarginal kineties were lacking. The macronucleus comprised one irregular
      shaped transverse nodule and two smaller roughly ellipsoid longitudinal nodules.

PMID- 17524632
TI  - Planktonic dinoflagellates of the northern Levantine Basin, northeastern
      Mediterranean Sea.
AB  - In the present study, a checklist of planktonic dinoflagellates was prepared from
      studies conducted on the northeastern Mediterranean coast of Turkey and by
      evaluating previously conducted studies. The sampling areas included Iskenderun
      Bay, the coast near Karatas at the west end of the Bay, and Babadillimani Bight,
      situated at the west of Mersin Bay, and its surroundings. The data of the present
      study derives from over 90 locations visited between 1994 and 2004. A total of
      174 taxa were reported. Ceratium (57 taxa) and Protoperidinium (28 taxa) were the
      most species-rich genera. The most common taxa were Ceratium kofoidii, Ceratium
      trichoceros, Ceratium tripos var. atlanticum, Protoperidinium divergens,
      Protoperidinium steinii, Ceratocorys horrida, Goniodoma acuminatum and Gonyaulax
      polygramma. Toxic species such as Dinophysis caudata, Dinophysis tripos were
      reported, and Scrippsiella trochoidea and Prorocentrum micans, which are known as
      red tide species elsewhere, were also common. The number of species is similar to
      those along other coasts of the Levantine Basin. However, some species were
      observed that had not previously been reported for the Levantine Basin, which can
      be attributed to the fact that the number of studies conducted in the region has
      increased and that new species may have entered the environment.

PMID- 17524633
TI  - High-dose radiotherapy in the management of chordoma and chondrosarcoma of the
      skull base and cervical spine: Part 1--Clinical outcomes.
AB  - AIMS: Patients with chordoma and chondrosarcoma in the skull base present a
      complex multidisciplinary problem. These tumours are rare and occur in difficult
      anatomical regions. We reviewed the local control and survival of patients
      treated in our centre. MATERIALS AND METHODS: Between 1996 and 2005, 12 adult
      cases of chordoma (nine) and chondrosarcoma (three) in the skull base or cervical
      spine were treated in our centre. The median follow-up is currently 38 months.
      One patient was treated with palliative intent. In 10 cases the prescription dose
      was 65 Gy in 39 fractions. The target volumes were measured, and the target
      maximum and minimum doses and the equivalent uniform dose (EUD) for the phase I
      plans were recorded. RESULTS: Local control was achieved in 11 of 12 cases. One
      chordoma patient failed locally, and one other died of metastatic disease despite
      local control. The 3- and 5-year cause-specific survival for the series was 88
      and 75%, respectively. The mean phase I planning target volume (PTV) was 120.4
      cm(3). The median minimum dose in the phase I PTV was 81.0%. The median EUD
      (expressed as a percentage of the prescribed dose) for the phase I PTV,
      calculated using a value for the exponent a of -15, was 98.3%. The phase I EUD
      was below 80% in two of the 12 cases. CONCLUSIONS: Our results confirm a need for
      aggressive local surgery and high-dose radiotherapy, and endorse
      multidisciplinary working. Although charged particle therapy is accepted as
      providing optimal treatment plans, in eight of our patients travel abroad would
      not have been feasible. This series provides encouraging results for carefully
      planned photon conformal radiotherapy, carried out in close collaboration with a
      specialist surgical team.

PMID- 17524634
TI  - Mating system in the tarantula spider Eupalaestrus weijenberghi (Thorell, 1894):
      evidences of monandry and polygyny.
AB  - The road tarantula Eupalaestrus weijenberghi shows a strongly female-biased sex
      ratio since adult females live several years while adult males live only for 2
      months. In this scenario selective males could be expected. However, several
      factors such as the rates of reproduction of each sex, degree of sexual
      selectivity and synchronicity of female receptiveness determine the operational
      sexual ratio and mating system of the species. Our objective was to determine the
      mating rates and mating tactics for females and males of E. weijenberghi and
      their variation throughout the reproductive period. Four hundred sexual
      encounters among 20 females and 20 males in all possible pair-wise combinations
      were carried out during 29 days, a brief but intense experimental period, as it
      also occurs in the field. Mating success differed strongly between sexes. Females
      mated once: five females mated at the first attempt, eight initially rejected
      males and copulated in subsequent attempts. Half of the males did not copulate
      and the others copulated 1-3 times. Mated females actively rejected males.
      Results indicate a mating system with monogamous females and polygamous males.
      Not all the females were receptive in every reproductive season. We suggest that
      female monogamy drastically affects the operational sex ratio, since several
      females were unreceptive after a single copulation, directly diminishing the male
      potential reproductive rate. This is the first experimental approach to estimate
      tarantula mating systems, their determinants and the consequences of the
      strategies shown by each sex.

PMID- 17524635
TI  - WITHDRAWN: Star activity of the type II restriction endonuclease OfoI.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17524636
TI  - Rhizosphere microbial community structure at different maize plant growth stages
      and root locations.
AB  - The aims of the present work were (1) to determine the influence of plant growth
      stages on the population size of culturable bacteria and fungi associated with
      rhizoplane and endo-rhizosphere of maize grown in field and (2) to establish the
      community structure of total culturable bacteria and fungi. Density, diversity
      and community structure of culturable rhizoplane and endo-rhizosphere populations
      at different maize plant growth stages were estimated. Plant development did not
      have influence on total culturable microflora density but it selectively
      influenced some bacterial and fungal groups present in the rhizosphere. However,
      the microbial community structure changed markedly over time. This knowledge is
      relevant for exploring endophytic rhizobacteria potential in the promotion of
      plant-growth, protection against pathogens and to detect perturbations in natural
      agro ecosystems.

PMID- 17524637
TI  - Enhancement of docetaxel efficacy in head and neck cancer treatment by G0 cell
      stimulation.
AB  - OBJECTIVES: Docetaxel has recently taken part in new chemotherapy regimens with
      promising activity especially in the first line therapy (induction chemotherapy)
      of head and neck cancer (SCCHN). Nevertheless a major problem concerning the
      response of SCCHN to chemotherapy is the high percentage of resting cells (G0
      phase cells) being resistant to chemotherapy. To overcome this phenomenon we have
      investigated the capacity of several cytokines to switch on cells into division
      cycle and progress to the chemosensitive phases (S, M-phase). METHODS: Il-6,
      Serotonin, G-CSF and EGF were used to stimulate G0-phase squamous cell cancer
      cells (Detroit 562, A431, UM-SCC 10B) for reentry in the cell cycle to enhance
      the response to docetaxel. The proportion of G0-phase cells was detected through
      multicolor FACS analysis and Ki67 staining. RESULTS: Cell cycle reentering was
      most effective after combination treatment with Serotonin+EGF. The proportion of
      G0 phase cells was significantly reduced after stimulation with Serotonin+EGF
      (p<0.05). Corresponding to cell cycle reentry the cytotoxic effect of docetaxel
      was significantly (p<0.04) enhanced in the prestimulated cells compared to the
      control (docetaxel monotreatment). CONCLUSIONS: Our investigations demonstrate
      for the first time that sensitizing G0 phase squamous cell carcinoma cells for
      docetaxel treatment is possible by prestimulation with target cytokines.
      Considering that up to 95% of tumor cells are in the resting (G0) phase of the
      cell cycle at the initiation of chemotherapy, prestimulation with EGF and
      serotonin could contribute to a synchronization of cancer cells. This would
      clearly enhance the cytotoxic effect.

PMID- 17524638
TI  - Mutation analysis of the MYH gene in unrelated Czech APC mutation-negative
      polyposis patients.
AB  - Some of the APC negative FAP and AFAP cases have recently been found to be
      attributable to MYH associated polyposis (MAP). MAP is an autosomal recessive
      syndrome associated with 5-100 colorectal adenomas and caused by mutation in the
      MYH gene. Here, we screened for germline MYH mutations in 82 APC-mutation
      negative probands with classical and attenuated familial adenomatous polyposis
      using the denaturing high performance liquid chromatography (DHPLC) method in
      combination with sequencing. Altogether 12 previously reported changes and four
      novel genetic alterations, mostly in intronic sequences, were identified. The
      results revealed the presence of biallelic germline MYH mutations in two
      patients. These patients were compound heterozygotes for two of the most common
      germline mutations c.494 A>G (p.Y165C); c.1,145 G>A (p.G382D). These variants are
      established to be associated with adenomatous polyposis and colorectal cancer. No
      novel pathogenic mutation has been identified in our study.

PMID- 17524639
TI  - Discovery of para-alkylthiophenoxyacetic acids as a novel series of potent and
      selective PPARdelta agonists.
AB  - A novel series of potent and selective PPARdelta agonists, para
      alkylthiophenoxyacetic acids, was identified. The synthesis and structure
      activity relationships are described.

PMID- 17524640
TI  - Synthesis and biological evaluation of L-cysteine derivatives as mitotic kinesin
      Eg5 inhibitors.
AB  - Inhibition of Eg5 represents a novel approach for the treatment of cancer. Here,
      we report the synthesis and structure-activity relationship of S-trityl-L
      cysteine (STLC) derivatives as Eg5 inhibitors. Some of these derivatives such as
      4f demonstrated enhanced inhibitory activity against Eg5 and induced mitotic
      arrest with characteristic monoastral spindles in HeLa cells.

PMID- 17524641
TI  - 3-Arylamino-2H-1,2,4-benzothiadiazin-5-ol 1,1-dioxides as novel and selective
      CXCR2 antagonists.
AB  - A series of 3-arylamino-2H-1,2,4-benzothiadiazin-5-ol 1,1-dioxides were prepared
      and shown to be novel and selective antagonists of the CXCR2 receptor. Synthesis,
      structure and activity relationships, selectivity, and some developability
      properties are described.

PMID- 17524642
TI  - Novel linear polymers bearing thiosialosides as pendant-type epitopes for
      influenza neuraminidase inhibitors.
AB  - A conventional synthesis of alpha-thioglycoside of sialic acid as a glycomonomer
      was accomplished. Radical copolymerization of the glycomonomer with vinyl acetate
      proceeded smoothly to afford a new class of glycopolymers having thiosialoside
      residues, in which all protection was removed by a combination of
      transesterification and saponification to provide a water-soluble thiosialoside
      cluster. The results of a preliminary study on biological responses against
      influenza virus neuraminidases using the thiosialoside polymer as a candidate for
      a neuraminidase inhibitor showed that the glycopolymer has potent inhibitory
      activity against the neuraminidases.

PMID- 17524643
TI  - Phenylpropanoic acid derivatives bearing a benzothiazole ring as PPARdelta
      selective agonists.
AB  - To find novel PPARdelta-selective agonists, we designed and synthesized
      phenylpropanoic acid derivatives bearing 6-substituted benzothiazoles.
      Optimization of this series led to the identification of a potent and selective
      PPARdelta agonist 17. Molecular modeling suggested that compound 17 occupies the
      Y-shaped pocket of PPARdelta appropriately.

PMID- 17524644
TI  - Local retinal circuits of melanopsin-containing ganglion cells identified by
      transsynaptic viral tracing.
AB  - Intrinsically photosensitive melanopsin-containing retinal ganglion cells
      (ipRGCs) control important physiological processes, including the circadian
      rhythm, the pupillary reflex, and the suppression of locomotor behavior (reviewed
      in [1]). ipRGCs are also activated by classical photoreceptors, the rods and
      cones, through local retinal circuits [2, 3]. ipRGCs can be transsynaptically
      labeled through the pupillary-reflex circuit with the derivatives of the Bartha
      strain of the alphaherpesvirus pseudorabies virus(PRV) [4, 5] that express GFP [6
      12]. Bartha-strain derivatives spread only in the retrograde direction [13].
      There is evidence that infected cells function normally for a while during GFP
      expression [7]. Here we combine transsynaptic PRV labeling, two-photon laser
      microscopy, and electrophysiological techniques to trace the local circuit of
      different ipRGC subtypes in the mouse retina and record light-evoked activity
      from the transsynaptically labeled ganglion cells. First, we show that ipRGCs are
      connected by monostratified amacrine cells that provide strong inhibition from
      classical-photoreceptor-driven circuits. Second, we show evidence that
      dopaminergic interplexiform cells are synaptically connected to ipRGCs. The
      latter finding provides a circuitry link between light-dark adaptation and ipRGC
      function.

PMID- 17524645
TI  - Mechanical signatures of transducer gating in the Drosophila ear.
AB  - Hearing relies on dedicated mechanotransducer channels that convert sound-induced
      vibrations into electrical signals [1]. Linking this transduction to identified
      proteins has proven difficult because of the scarcity of native auditory
      transducers and their tight functional integration into ears [2-4]. We describe
      an in vivo paradigm for the noninvasive study of auditory transduction. By
      investigating displacement responses of the Drosophila sound receiver, we
      identify mechanical signatures that are consistent with a direct
      mechanotransducer gating in the fly's ear. These signatures include a nonlinear
      compliance that correlates with electrical nerve responses, shifts with
      adaptation, and conforms to the gating-spring model of vertebrate auditory
      transduction. Analyzing this gating compliance in terms of the gating-spring
      model reveals striking parallels between the transducer mechanisms for hearing in
      vertebrates and flies. Our findings provide first insights into the mechanical
      workings of invertebrate mechanotransducer channels and set the stage for using
      Drosophila to specifically search for, and probe the roles of, auditory
      transducer components.

PMID- 17524646
TI  - Coding of azimuthal directions via time-compensated combination of celestial
      compass cues.
AB  - Many animals use the sun as a reference for spatial orientation [1-3]. In
      addition to sun position, the sky provides two other sources of directional
      information, a color gradient [4] and a polarization pattern [5]. Work on insects
      has predominantly focused on celestial polarization as an orientation cue [6, 7].
      Relying on sky polarization alone, however, poses the following two problems: E
      vector orientations in the sky are not suited to distinguish between the solar
      and antisolar hemisphere of the sky, and the polarization pattern changes with
      changing solar elevation during the day [8, 9]. Here, we present neurons that
      overcome both problems in a locust's brain. The spiking activity of these neurons
      depends (1) on the E vector orientation of dorsally presented polarized light,
      (2) on the azimuthal, i.e., horizontal, direction, and (3) on the wavelength of
      an unpolarized light source. Their tuning to these stimuli matches the
      distribution of a UV/green chromatic contrast as well as the polarization of
      natural skylight and compensates for changes in solar elevation during the day.
      The neurons are, therefore, suited to code for solar azimuth by concurrent
      combination of signals from the spectral gradient, intensity gradient, and
      polarization pattern of the sky.

PMID- 17524647
TI  - The potential applications of a virtual moving environment for assessing falls in
      elderly adults.
AB  - The purpose of this study was to investigate whether the moving room paradigm
      could be used to assess fall risk in older people. A group of young adults (18-29
      years) and two groups of elderly adults (60-79 years) with and without a history
      of falls were placed into a simulated moving room. Participants stood still
      facing an oscillating three dimensional virtual room moving in the antero
      posterior plane with three types of room movement conditions, continuous
      oscillatory, discrete anterior and discrete posterior. The young adults performed
      with less postural motion and coherence with the virtual motion than the older
      age groups. The group of elderly fallers exhibited more postural motion [center
      of pressure (COP) length, p<0.05], a trend towards higher coherence with the
      object motion (p=0.07), and the greatest amount of time-to-stability (p<0.05). A
      virtual moving room incorporating measures of time-to-stability and egomotion
      appears useful in predicting risk for falls.

PMID- 17524648
TI  - Methodological and interpretive issues in posture-cognition dual-tasking in
      upright stance.
AB  - The traditionally separate researches on cognitive functions and basic
      coordinations such as stance and locomotion are coming together in the study of
      posture-cognition dual-tasking. The importance of this growing research area lies
      not only in the ubiquitous coexistence of postural and cognitive tasks but also
      in the observation that posture control very often has the dual role of securing
      the body's safety and balance while also providing a versatile, stable physical
      substrate well-suited to perception-action tasks. Although dual-task
      investigations strongly suggest that posture control and higher level cognition
      have common resource requirements, inconsistencies in the data and differences in
      experimental design make it difficult to distill a fuller understanding of the
      specific mechanisms behind posture-cognition dual-tasking. In this paper, we
      review the literature on upright standing with concurrent cognitive tasks, and
      highlight paradigmatic variations that possibly contribute to dual-task data
      differences. Implications arising from theoretical assumptions made about the
      role of postural control in the concurrent performance of cognitive tasks are
      also discussed.

PMID- 17524649
TI  - New understanding of the group A Streptococcus pathogenesis cycle.
AB  - Group A Streptococcus (GAS) has long been recognized as a human pathogen causing
      an exceptionally broad range of infections. Despite intense research, however,
      the molecular mechanisms of GAS disease remain unclear. Recently, many important
      discoveries have been made that shed light on GAS pathogenesis and open exciting
      avenues for future research. Advances in genome sequencing, microarray technology
      and proteomic analysis, in combination with the development of more suitable
      animal models, have markedly increased our knowledge of the mechanisms underlying
      GAS pathogenesis. The information gained from these studies will translate into
      improved diagnostics and new targets for therapeutic drugs and vaccines.

PMID- 17524650
TI  - Revision of Oxford medial unicompartmental knee arthroplasty to total knee
      arthroplasty - results of a multicentre study.
AB  - The advantages of Unicompartmental Knee Replacement (UKR) over Total Knee
      Replacement (TKR) includes the preservation of soft tissue as well as bone stock,
      and better function with improved range of motion and more natural gait. It is
      therefore believed that the revision of failed UKR to TKR is technically easier
      than revision of failed TKR. In our study we tested this hypothesis by assessing
      the reconstruction requirements and early clinical and radiological outcome
      following the revision of UKR to TKR. During a 15-year period 1060 primary Oxford
      medial UKR procedures were performed at three centres, 36 of which underwent
      revision to TKR due to aseptic failure. The mean operating time for revision
      surgery was 113 min. Among the revision prostheses used, 28 were standard TKRs,
      six were constrained, and two were semi-constrained. Thirty had no intramedullary
      stems whereas six had intramedullary stems. In 30 cases reconstruction for bone
      loss was not required whereas metal augmentation was used in two knees, contained
      peg defects in the femur were filled with cement in two knees and contained keel
      defects in the tibia were grafted using the bone from revision cuts in two knees.
      After a mean follow-up of 2 years, the mean 'total knee score' was 86.3 and the
      mean functional score was 78.5. These findings suggest that the complexity of
      operation and complications encountered during Oxford medial UKR revision and the
      clinical outcome compare favorably with those of TKR revision.

PMID- 17524652
TI  - QSAR study of selective ligands for the thyroid hormone receptor beta.
AB  - In this paper, an accurate and reliable QSAR model of 87 selective ligands for
      the thyroid hormone receptor beta 1 (TRbeta1) was developed, based on theoretical
      molecular descriptors to predict the binding affinity of compounds with receptor.
      The structural characteristics of compounds were described wholly by a large
      amount of molecular structural descriptors calculated by DRAGON. Six most
      relevant structural descriptors to the studied activity were selected as the
      inputs of QSAR model by a robust optimization algorithm Genetic Algorithm. The
      built model was fully assessed by various validation methods, including internal
      and external validation, Y-randomization test, chemical applicability domain, and
      all the validations indicate that the QSAR model we proposed is robust and
      satisfactory. Thus, the built QSAR model can be used to fast and accurately
      predict the binding affinity of compounds (in the defined applicability domain)
      to TRbeta1. At the same time, the model proposed could also identify and provide
      some insight into what structural features are related to the biological activity
      of these compounds and provide some instruction for further designing the new
      selective ligands for TRbeta1 with high activity.

PMID- 17524651
TI  - Novel isomarabarican triterpenes, exhibiting selective anti-proliferative
      activity against vascular endothelial cells, from marine sponge Rhabdastrella
      globostellata.
AB  - Four novel globostellatic acid X methyl esters (1-4) having isomarabarican-type
      triterpenoidal skeleton and three related new compounds (5-7) were isolated from
      the marine sponge Rhabdastrella globostellata, as selective anti-proliferative
      agents against human umbilical vein endothelial cells (HUVECs). Those chemical
      structures were elucidated by the detailed 2D NMR analysis. Two globostellatic
      acid X methyl esters (3 and 4) having 13E-geometry were found to inhibit
      proliferation of HUVECs, 80- to 250-fold selectively in comparison with several
      other cell lines. 13E,17E-Globostellatic acid X methyl ester (4) also inhibited
      bFGF-induced tubular formation and VEGF-induced migration of HUVECs. Moreover, 4
      induced apoptosis of HUVECs, whereas it exhibited no effect on VEGF-induced
      phosphorylation of ERK1/2 in HUVECs.

PMID- 17524653
TI  - Structure-activity relationships of semisynthetic mumbaistatin analogs.
AB  - Mumbaistatin (1), a new anthraquinone natural product, is one of the most potent
      known inhibitors of hepatic glucose-6-phosphate translocase, an important target
      for the treatment of type II diabetes. Its availability, however, has been
      limited due to its extremely low yield from the natural source. Starting from
      DMAC (5, 3,8-dihydroxyanthraquinone-2-carboxylic acid), a structurally related
      polyketide product of engineered biosynthesis, we developed a facile
      semisynthetic method that afforded a variety of mumbaistatin analogs within five
      steps. This work was facilitated by the initial development of a DMAC
      overproduction system. In addition to reinforcing the biological significance of
      the anthraquinone moiety of mumbaistatin, several semisynthetic analogs were
      found to have low micromolar potency against the translocase in vitro. Two of
      them were also active in glucose release assays from primary hepatocytes. The
      synergistic combination of biosynthesis and synthesis is a promising avenue for
      the discovery of new bioactive substances.

PMID- 17524655
TI  - Design, syntheses, and antitumor activity of novel chromone and aurone
      derivatives.
AB  - A series of new chromone analogues bearing heterocyclic thioether moiety and
      aurone analogues bearing cyclic tertiary amine moiety were designed and
      synthesized under microwave irradiation. The synthetic protocol was found to
      present many advantages, such as higher yields, shorter reaction time (10-20
      min), mild condition, and readily isolation of the products. The synthesized
      compounds were assayed for their antitumor activity against four kinds of human
      solid tumor cell lines including HCCLM-7, Hep-2, MDA-MB-435S, and SW-480. Two
      compounds, (Z)-2-((4-benzyl-piperazin-1-yl)methylene)benzofuran-3(2H)-one 5e and
      (Z)-2-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methylene)benzofuran-3(2H)
      one 5f, were identified as the most promising candidates with the IC(50) values
      in the range of 4.1-13.1 microM. Further cell cycle studies revealed that
      compounds 5e and 5f arrest the cell cycle in G(0)/G(1) phase and displayed
      apoptosis-inducing effect on Hep-2 cells.

PMID- 17524654
TI  - Synthesis of neutral and cationic tripyridylporphyrin-D-galactose conjugates and
      the photoinactivation of HSV-1.
AB  - Neutral and cationic tripyridylporphyrin-D-galactose conjugates were synthesized
      and their antiviral activity against herpes simplex virus type 1 (HSV-1) was
      evaluated. At non-cytotoxic concentrations the studied compounds show significant
      antiviral activity after photoactivation. The influence of photoactivation on
      drug treated cells was also analyzed, at different times of infection with HSV-1,
      for a neutral (1b) and a cationic glycoporphyrin (3b) derivative. The results
      show that the inhibition of the viral yield is more dependent on photoactivation
      for compound 1b than for compound 3b. These two compounds also differ in the
      inhibitory effect during the viral replicative cycle: while compound 3b inhibits
      the viral yield at all the addition times assayed, compound 1b is more efficient
      in later times of infection.

PMID- 17524656
TI  - Interspecies compatibility of NAS1 gene promoters.
AB  - Nicotianamine and nicotianamine synthase (NAS) play key roles in iron nutrition
      in all higher plants. However, the mechanism underlying the regulation of NAS
      expression differs among plant species. Sequences homologous to iron deficiency
      responsive elements (IDEs), i.e., cis-acting elements, are found on the promoters
      of these genes. We aimed to verify the interspecies compatibility of the Fe
      deficiency response of NAS1 genes and understand the universal mechanisms that
      regulate their expression patterns in higher plants. Therefore, we introduced the
      graminaceous (Hordeum vulgare L. and Oryza sativa L.) NAS1 promoter::GUS into
      dicots (Nicotiana tabacum L. and Arabidopsis thaliana L.). Fe deficiency induced
      HvNAS1 expression in the shoots and roots when introduced into rice. HvNAS1
      promoter::GUS and OsNAS1 promoter::GUS induced strong expression of GUS under Fe
      deficient conditions in transformed tobacco. In contrast, these promoters only
      definitely functioned in Arabidopsis transformants. These results suggest that
      some Fe nutrition-related trans-factors are not compatible between graminaceous
      plants and Arabidopsis. HvNAS1 promoter::GUS induced GUS activity only in the
      roots of transformed tobacco under Fe-deficient conditions. On the other hand,
      OsNAS1 promoter::GUS induced GUS activity in both the roots and shoots of
      transformed tobacco under conditions of Fe deficiency. In tobacco transformants,
      the induction of GUS activity was induced earlier in the shoots than roots. These
      results suggest that the HvNAS1 and OsNAS1 promoters are compatible with Fe
      acquisition-related trans-factors in the roots of tobacco and that the OsNAS1
      promoter is also compatible with some shoot-specific Fe deficiency-related trans
      factors in tobacco.

PMID- 17524657
TI  - Proteomic and genetic analysis of glycinin subunits of sixteen soybean genotypes.
AB  - We investigated proteomic and genomic profiles of glycinin, a family of major
      storage proteins in 16 different soybean genotypes consisting of four groups
      including wild soybean (Glycine soja), unimproved cultivated soybean landraces
      from Asia (G. max), ancestors of N. American soybean (G. max), and modern soybean
      (G. max) genotypes. We observed considerable variation in all five glycinin
      subunits, G1, G2 G3, G4 and G5 using proteomics and genetic analysis. Two
      dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry
      (MS) analysis showed that the wild genotypes had a range of 25-29 glycinin
      protein spots that included both acidic and basic polypeptides followed by the
      ancestors with 24-28, modern cultivars with 24-25, and landraces with 17-23
      protein spots. Overall, the wild genotypes have a higher number of protein spots
      when compared to the other three genotypes. Major variation was observed in
      acidic polypeptides of G3, G4 and G5 compared to G1 and G2, and minor variation
      was observed in basic polypeptides of all subunits. Our data indicated that there
      are major variations of glycinin subunits between wild and cultivated genotypes
      rather than within the same groups. Based on Southern blot DNA analysis, we
      observed genetic polymorphisms in group I genes (G1, G2, and G3) between and
      within the four genotype groups, but not in group II genes (G4 and G5). This is
      the first study reporting the comparative analysis of glycinin in a diverse set
      of soybean genotypes using combined proteomic and genetic analysis.

PMID- 17524658
TI  - Osteosynthetic thoracic stabilization after complete resection of the sternum.
AB  - We present a case of a 66-year-old diabetic patient with chronic non-healing
      sternum after CABG operation. After four attempts of sternum refixation within 2
      years, the need of bone debridement resulted in a nearly complete loss of
      sternum. Finally, a mesh graft and a pectoralis muscle flap were used to bridge
      the sternal space. Despite good wound healing, the thoracic instability led to
      intolerable chest pain persisting over the next years. In this case report, we
      describe the successful thoracic stabilization by using transverse plate
      fixation, which resulted in perfect thoracic stabilization and immediate
      cessation of pain.

PMID- 17524660
TI  - The value of video-assisted mediastinoscopy in pulmonary metastasectomy.
AB  - OBJECTIVE: To assess the role of video-assisted mediastinoscopy (VAM) in
      identifying involved mediastinal lymph nodes in patients undergoing pulmonary
      metastasectomy. METHODS: Over a 4-year period (2002-2005) a retrospective study
      was carried out in 57 patients (44 men, 13 women, mean age 59 years) undergoing
      isolated, unilateral or bilateral metastasectomy. Following staging CT scan, VAM
      was performed prior to open thoracotomy, median sternotomy or VATS resection of
      the metastasis. Follow-up was complete in all patients. RESULTS: Fifty-seven
      patients underwent 62 operations for metastatic disease. The majority had
      colorectal cancer (39) followed by renal (11), sarcoma (9), liver (2) and
      miscellaneous (8). Six patients (10.5%) had positive mediastinal nodes on VAM.
      There was no perioperative morbidity or mortality. At a median follow-up of 25
      months, 63 patients (68.5%) were still alive. CONCLUSIONS: Mediastinal lymph node
      involvement has been reported to occur in up to 14% of patients with pulmonary
      metastasis. In our study, 10% of patients treated for pulmonary metastasis had
      positive nodal disease at metastasectomy. We believe our results confirm that VAM
      can be safely performed and may have a role in more accurate staging of
      metastatic disease and influence the decision for post-resection adjuvant
      therapy.

PMID- 17524661
TI  - Modulation of TSHR signaling by posttranslational modifications.
AB  - Posttranslational modifications of seven transmembrane receptors (7TMRs) affect
      their function to a large extent. Many studies of glycosylation or
      phosphorylation of 7TMRs have shown that these modifications influence the cell
      surface expression or signaling of the receptor. Recently, other types of
      posttranslational modifications of the thyrotropin-stimulating hormone receptor
      (TSHR) have been characterized, including sialylation and dimerization. Increased
      TSHR sialylation results in increased TSHR cell-surface expression. Furthermore,
      TSHR oligomerization and the probable modification of TSHR signaling in lipid
      rafts require further clarification with regard to their functional consequences.
      In addition to its known coupling to Galphas and Galphaq, and possibly other G
      proteins, the TSHR also couples to further signaling pathways, such as the
      mitogen-activated protein kinase (MAPK) pathway, which involves G-protein-coupled
      receptor kinases (GRKs) and arrestins. We discuss these emerging new findings and
      their implications for signaling of the TSHR.

PMID- 17524662
TI  - Inhibition of extracellular signal-regulated kinase (ERK1/2) activity reverses
      endotoxin-induced hypotension via decreased nitric oxide production in rats.
AB  - Overproduction of reactive oxygen and nitrogen species leads to oxidative stress
      and decreased total antioxidant capacity, which is responsible for high mortality
      from several inflammatory diseases such as endotoxic shock. Among reactive
      nitrogen species, nitric oxide (NO) produced by inducible NO synthase (iNOS)
      during endotoxemia is the major cause of vascular hyporeactivity, hypotension and
      multiple organ failure. This study was conducted to determine if mitogen
      activated protein kinases (MAPKs) such as extracellular signal-regulated kinase
      (ERK1/2) contributes to endotoxin-induced hypotension as well as vascular
      inflammation and oxidative stress via NO production. In conscious male Wistar
      rats, injection of endotoxin (10 mg kg(-1), i.p.) caused a decrease in mean
      arterial pressure (MAP) for 4h and increased levels of nitrite in serum, aorta
      and mesenteric artery. These effects of endotoxin were prevented by selective
      inhibition of ERK1/2 phosphorylation by MAPK kinase (MEK1/2) with U0126 (5 mg kg(
      1), i.p.; 1h after endotoxin). Endotoxin also caused an increase in protein
      levels of phosphorylated ERK1/2 in aorta which was abolished by U0126. Selective
      inhibition of iNOS with phenylene-1,3-bis[ethane-2-isothiourea] dihydrobromide
      (1,3-PBIT) (10 mg kg(-1), i.p.; 1h after endotoxin) did not change the endotoxin
      induced increase in ERK1/2 activity. Myeloperoxidase activity was increased in
      aorta and decreased in mesenteric artery by endotoxin, which was reversed by
      U0126. Endotoxin-induced decrease in one of the products of lipid peroxidation,
      malonedialdehyde (MDA) was prevented by U0126 in mesenteric artery; however,
      U0126 caused a further decrease in the levels of MDA in aorta. These data suggest
      that increased phosphorylation of ERK1/2 by MEK1/2 contributes to the endotoxin
      induced hypotension via NO production rat aorta and mesenteric artery. It is
      likely that ERK1/2 mediates the effect of endotoxin on MPO activity in a
      different degree in the tissues suggesting possible involvement of any mediator
      and/or mechanism which also causes neutrophil infiltration during inflammatory
      response at least in mesenteric artery. Moreover, ERK1/2 seems to be involved in
      the endotoxin-induced increase in total antioxidant capacity in mesenteric
      artery.

PMID- 17524663
TI  - Automation of random conical tilt and orthogonal tilt data collection using
      feature-based correlation.
AB  - Visualization by electron microscopy has provided many insights into the
      composition, quaternary structure, and mechanism of macromolecular assemblies. By
      preserving samples in stain or vitreous ice it is possible to image them as
      discrete particles, and from these images generate three-dimensional structures.
      This 'single-particle' approach suffers from two major shortcomings; it requires
      an initial model to reconstitute 2D data into a 3D volume, and it often fails
      when faced with conformational variability. Random conical tilt (RCT) and
      orthogonal tilt (OTR) are methods developed to overcome these problems, but the
      data collection required, particularly for vitreous ice specimens, is difficult
      and tedious. In this paper, we present an automated approach to RCT/OTR data
      collection that removes the burden of manual collection and offers higher quality
      and throughput than is otherwise possible. We show example datasets collected
      under stain and cryo conditions and provide statistics related to the efficiency
      and robustness of the process. Furthermore, we describe the new algorithms that
      make this method possible, which include new calibrations, improved targeting and
      feature-based tracking.

PMID- 17524664
TI  - Unique helical conformation of the fourth cytoplasmic loop of the CB1 cannabinoid
      receptor in a negatively charged environment.
AB  - The proximal portion of the C-terminus of the CB(1) cannabinoid receptor is a
      primary determinant for G-protein activation. A 17 residue proximal C-terminal
      peptide (rodent CB1 401-417), the intracellular loop 4 (IL4) peptide, mimicked
      the receptor's G-protein activation domain. Because of the importance of the
      cationic amino acids to G-protein activation, the three-dimensional structure of
      the IL4 peptide in a negatively charged sodium dodecyl sulfate (SDS) micellar
      environment has been studied by two-dimensional proton nuclear magnetic resonance
      (2D (1)H NMR) spectroscopy and distance geometry calculations. Unambiguous proton
      NMR assignments were carried out with the aid of correlation spectroscopy (DQF
      COSY and TOCSY) and nuclear Overhauser effect spectroscopy (NOESY and ROESY)
      experiments. The distance constraints were used in torsion angle dynamics
      algorithm for NMR applications (DYANA) to generate a family of structures which
      were refined using restrained energy minimization and dynamics. In water, the IL4
      peptide prefers an extended conformation, whereas in SDS micelles, 3(10)-helical
      conformation is induced. The predominance of 3(10)-helical domain structure in
      SDS represents a unique difference compared with structure in alternative
      environments, which can significantly impact global electrostatic surface
      potential on the cytoplasmic surface of the CB(1) receptor and might influence
      the signal to the G-proteins.

PMID- 17524666
TI  - Anterior cingulate pathology and social cognition in schizophrenia: a study of
      gray matter, white matter and sulcal morphometry.
AB  - The anterior cingulate gyrus (ACG) is a critical structure for social cognitive
      processing; the pathology of this structure might be a major source of social
      dysfunction in schizophrenia. Multiple structural abnormalities of the ACG have
      been demonstrated in schizophrenia including changes in gray matter volume, white
      matter microstructures and macroscopic sulcal morphology. However, the
      interrelationships among these different abnormalities have not been
      investigated. Thus, the relationship between structural abnormalities in the ACG
      and social cognition in schizophrenia remains to be elucidated. Magnetic
      resonance imaging data were acquired at 3.0 T from 26 schizophrenic patients and
      20 healthy participants. We performed anterior cingulate cortex (ACC) volumetry,
      evaluated diffusion tensor imaging of the anterior cingulum, analyzed
      paracingulate/cingulate sulcus (PCS/CS) morphology and investigated the
      interrelationships among these measures. We also investigated the association
      between ACG structural abnormalities and psychopathology, and the social
      cognition ability of schizophrenic patients as estimated by emotion attribution
      tasks. Compared with healthy subjects, schizophrenic patients exhibited reduced
      ACC volume, decreased fractional anisotropy in the anterior cingulum bilaterally
      and a poorly developed PCS/CS in the left hemisphere. No interrelationship was
      identified among these measures in the schizophrenic group. Schizophrenic
      patients performed poorly on emotion attribution tasks. Importantly, clinical
      symptoms and performance on emotion attribution subtasks were associated with ACC
      volumes and left PCS/CS variation in different ways. These results suggested that
      pathology of the ACC, anterior cingulum and PCS/CS is, at least partially,
      independent and has differential impacts on psychopathology and social cognitive
      impairment in schizophrenia.

PMID- 17524667
TI  - Age-related alterations of the functional interactions within the basal ganglia
      and cerebellar motor loops in vivo.
AB  - Aging may alter the motor functions of the basal ganglia and cerebellum; however,
      no previous neuroimaging study has investigated the effect of aging on the
      functional connectivity of the motor loops involving these structures. Recently,
      using fMRI with a parametric approach and structural equation modeling (SEM), we
      demonstrated a significant functional interaction within the basal ganglia
      thalamo-motor (BGTM) loop during self-initiated (SI) finger movement in young
      normal subjects, whereas cerebro-cerebellar (CC) loop was mainly involved during
      externally triggered (ET) movement. We applied this method to 12 normal aged
      subjects (53-72 years old) in order to study the effect of age on BGTM and CC
      loops. Compared with the functional connectivity seen in young subjects, SEM
      showed decreased connectivity in BGTM loops during SI task, decreased interaction
      in the CC loop during ET task, and increased connectivity within motor cortices
      and between hemispheres during both types of tasks. These results suggest an age
      related decline of cortico-subcortical connectivity with increased interactions
      between motor cortices. Aging effects on SI and ET movements are probably caused
      by functional alterations within BGTM and CC loops.

PMID- 17524665
TI  - CBF/CMRO2 coupling measured with calibrated BOLD fMRI: sources of bias.
AB  - The coupling between cerebral blood flow (CBF) and cerebral metabolic rate of
      oxygen (CMRO2) during brain activation can be characterized by an empirical index
      n, the ratio of fractional CBF changes to fractional CMRO2 changes. Measurements
      of n have yielded varying results, and it is not known if the observed
      variability is due to measurement techniques or underlying physiology. The
      calibrated BOLD approach using hypercapnia offers a promising tool for assessing
      changes in CBF/CMRO2 coupling in health and disease, but potential systematic
      errors have not yet been characterized. The goal of this study was to
      experimentally evaluate the magnitude of bias in the estimate of n that arises
      from the way in which a region of interest (ROI) is chosen for averaging data and
      to relate this potential bias to a more general theoretical consideration of the
      sources of systematic errors in the calibrated BOLD experiment. Results were
      compared for different approaches for defining an ROI within the visual cortex
      based on: (1) retinotopically defined V1; (2) a functional CBF localizer; and (3)
      a functional BOLD localizer. Data in V1 yielded a significantly lower estimate of
      n (2.45) compared to either CBF (n=3.45) or BOLD (n=3.18) localizers. Different
      statistical thresholds produced biases in estimates of n with values ranging from
      3.01 (low threshold) to 4.37 (high threshold). Possible sources of the observed
      biases are discussed. These results underscore the importance of a critical
      evaluation of the methodology, and the adoption of consistent standards for
      applying the calibrated BOLD approach to the evaluation of CBF/CMRO2 coupling.

PMID- 17524668
TI  - Unity and diversity of tonic and phasic executive control components in episodic
      and working memory.
AB  - The present study aimed to delineate the extent to which unitary executive
      functions might be shared across the separate domains of episodic and working
      memory. A mixed blocked/event-related functional magnetic resonance imaging
      (fMRI) design was employed to assess sustained (tonic control) and transient
      (phasic control) brain responses arising from incrementing executive demand
      (source versus item episodic memory - vis-a-vis - two-back versus one-back
      working memory) using load-dependent activation overlaps as indices of common
      components. Although an extensive portion of the regional load effects
      constituted differential control modulations in both sustained and transient
      responses, commonalities were also found implicating a subset of executive core
      mechanisms consistent with unitary or domain general control. 'Unitary' control
      modulations were temporally dissociated into (1) shared tonic components
      involving medial and lateral prefrontal cortex, striatum, cerebellum and superior
      parietal cortex, assumed to govern enhanced top-down context processing,
      monitoring and sustained attention throughout task periods and (2) stimulus
      synchronous phasic components encompassing posterior intraparietal sulcus,
      hypothesized to support dynamic shifting of the 'focus of attention' among
      internal representations. Taken together, these results converge with theoretical
      models advocating both unity and diversity among executive control processes.

PMID- 17524669
TI  - Neural correlates of perceptual difference between itching and pain: a human fMRI
      study.
AB  - It has been wondered why we can discriminate between itching and pain as
      different sensations. Several researchers have investigated neural mechanisms
      underlying their perceptual differences, and found that some C fibers and
      spinothalamic tract neurons had different sensitivity between itching and pain.
      These findings suggest that such differences in ascending pathways are partly
      associated with perceptual difference between itching and pain. However, it was
      still unclear how our brains distinguish itching from pain. Thus, by functional
      magnetic resonance imaging (fMRI) time series analysis, we investigated the
      neural substrates of perceptual differences between itching and pain. The
      anterior cingulate cortex, the anterior insula, the basal ganglia and the pre
      supplementary motor area were commonly activated by itching and pain. Neural
      activity in the posterior cingulate cortex (PCC) and the posterior insula
      associated with itching was significantly higher than that associated with pain
      and significantly proportional to itching sensation. Pain, but not itching,
      induced an activation of the thalamus for several minutes, and neural activity of
      this brain region significantly correlated to pain sensation. These findings
      demonstrate that the difference in the sensitivity of PCC, the posterior insula
      and the thalamus between itching and pain would be responsible for the perceptual
      difference between these sensations. The previous itching studies did not observe
      an activation of the secondary somatosensory cortex (S2) by itching. However, we
      observed that an activation of S2 by pain was not significantly different from
      that by itching, indicating that S2 was associated with not only pain but also
      itching.

PMID- 17524670
TI  - Independent contributions of cortical gray matter atrophy and ventricle
      enlargement for predicting neuropsychological impairment in multiple sclerosis.
AB  - The primary goal of this study was to investigate associations between regional
      gray matter (GM) atrophy and neuropsychological function in multiple sclerosis
      (MS), while accounting for the influence of central brain atrophy (i.e. third
      ventricle enlargement). Using a cross-sectional design, we studied 59 MS patients
      with brain MRI and neuropsychological testing. Regional gray matter fractions
      (rGMFs) were calculated from MRI images for 11 homologous brain areas using the
      semiautomatic brain region extraction (SABRE) technique. Neuropsychological
      testing followed consensus panel guidelines and included tests emphasizing
      episodic memory, working memory and processing speed. The analytic approach was
      stepwise linear regression, with forward selection and p<0.05 threshold for
      significance. Consistent with previous research, there were significant
      correlations between third ventricle width and neuropsychological tests. Stepwise
      linear regression analyses controlling for third ventricle width retained rGMFs
      obtained from specific regions within the prefrontal cortex. Left frontal atrophy
      was associated with tests emphasizing auditory/verbal memory. Right frontal
      atrophy was associated with impairment in visual episodic and working memory. For
      the first time, we show an independent relationship between cortical atrophy and
      cognitive impairment after accounting for the effects of central atrophy.

PMID- 17524671
TI  - Neural correlates of regional EEG power change.
AB  - To clarify the physiological significance of task-related change of the regional
      electroencephalogram (EEG) rhythm, we quantitatively evaluated the correlation
      between regional cerebral blood flow (rCBF) and EEG power. Eight subjects
      underwent H2 15O positron emission tomography scans simultaneously with EEG
      recording during the following tasks: rest condition with eyes closed and open,
      self-paced movements of the right and left thumb and right ankle. EEG signals
      were recorded from the occipital and bilateral sensorimotor areas. Cortical
      activation associated with EEG rhythm generation was studied by the correlation
      between rCBF and EEG power. There were significant negative correlations between
      the sensorimotor EEG rhythm at 10-20 Hz on each side and the ipsilateral
      sensorimotor rCBF and between the occipital EEG rhythm at 10-20 Hz and the
      occipital rCBF. The occipital EEG rhythm showed a positive correlation with the
      bilateral medial prefrontal rCBF, while the right sensorimotor EEG rhythm showed
      a positive correlation with the left prefrontal rCBF. In conclusion, decrease in
      the regional EEG rhythm at 10-20 Hz might represent the neuronal activation of
      the cortex underlying the electrodes, at least for the visual and sensorimotor
      areas. The neural network including the prefrontal cortex could play an important
      role to generate the EEG rhythm.

PMID- 17524672
TI  - Selectivity and localization of cortical response to auditory and visual
      stimulation in awake infants aged 2 to 4 months.
AB  - To better understand the development of multimodal perception, we examined
      selectivity and localization of cortical responses to auditory and visual stimuli
      in young infants. Near-infrared optical topography with 24 channels was used to
      measure event-related cerebral oxygenation changes of the bilateral temporal
      cortex in 15 infants aged 2 to 4 months, when they were exposed to speech sounds
      lasting 3 s and checkerboard pattern reversals lasting 3 s, which were
      asynchronously presented with different alternating intervals. Group analysis
      revealed focal increases in oxy-hemoglobin and decreases in deoxy-hemoglobin in
      both hemispheres in response to auditory, but not to visual, stimulation. These
      results indicate that localized areas of the primary auditory cortex and the
      auditory association cortex are involved in auditory perception in infants as
      young as 2 months of age. In contrast to the hypothesis that perception of
      distinct sensory modalities may not be separated due to cross talk over the
      immature cortex in young infants, the present study suggests that unrelated
      visual events do not influence on the auditory perception of awake infants.

PMID- 17524673
TI  - Diffusion tensor MRI-based estimation of the influence of brain tissue anisotropy
      on the effects of transcranial magnetic stimulation.
AB  - We evaluate and discuss the relevance of fiber anisotropy in estimating the
      effect of transcranial magnetic stimulation (TMS) on the human brain. Finite
      element simulations were carried out on a three-dimensional model of the head
      that included anisotropic conductivity information derived from diffusion tensor
      imaging (DTI). The results show that anisotropy has minor effects both on the
      position of the main locus of activation and on its intensity. It has
      considerably more effect on the spatial distribution of the induced electric
      field, yielding differences of the order of 10% of the maximum induced field.
      Moreover the area affected by magnetic stimulation is slightly larger when we
      include fiber anisotropy in the calculations than in an isotropic model. We also
      show that the induced field observed in the anisotropic model does not always
      align with the local fiber orientation but rather follows specific patterns of
      parallelity. These findings will help to improve the estimation of the areas
      involved in magnetic stimulation.

PMID- 17524674
TI  - Support vector machine learning-based fMRI data group analysis.
AB  - To explore the multivariate nature of fMRI data and to consider the inter-subject
      brain response discrepancies, a multivariate and brain response model-free method
      is fundamentally required. Two such methods are presented in this paper by
      integrating a machine learning algorithm, the support vector machine (SVM), and
      the random effect model. Without any brain response modeling, SVM was used to
      extract a whole brain spatial discriminance map (SDM), representing the brain
      response difference between the contrasted experimental conditions. Population
      inference was then obtained through the random effect analysis (RFX) or
      permutation testing (PMU) on the individual subjects' SDMs. Applied to arterial
      spin labeling (ASL) perfusion fMRI data, SDM RFX yielded lower false-positive
      rates in the null hypothesis test and higher detection sensitivity for synthetic
      activations with varying cluster size and activation strengths, compared to the
      univariate general linear model (GLM)-based RFX. For a sensory-motor ASL fMRI
      study, both SDM RFX and SDM PMU yielded similar activation patterns to GLM RFX
      and GLM PMU, respectively, but with higher t values and cluster extensions at the
      same significance level. Capitalizing on the absence of temporal noise
      correlation in ASL data, this study also incorporated PMU in the individual-level
      GLM and SVM analyses accompanied by group-level analysis through RFX or group
      level PMU. Providing inferences on the probability of being activated or
      deactivated at each voxel, these individual-level PMU-based group analysis
      methods can be used to threshold the analysis results of GLM RFX, SDM RFX or SDM
      PMU.

PMID- 17524675
TI  - Neurophysiological correlates of sleepiness: a combined TMS and EEG study.
AB  - Changes of cortical and corticospinal excitability as a function of sleep
      deprivation have been studied, using EEG power maps and several TMS measures in
      33 normal subjects before and after a 40-h sleep deprivation (SD). The effects of
      SD were independently assessed by subjective and EEG measures of sleepiness, the
      latter being represented in terms of cortical maps for different frequency bands.
      Short intracortical facilitation (SICF) and inhibition (SICI) were measured by
      the paired-pulse TMS technique with different inter-stimulus intervals. Besides
      standardized motor threshold (MT), lower threshold (LT) and upper threshold (UT)
      were also determined. Subjective sleepiness severely increased as a consequence
      of SD, paralleled by a drastic decrease of alertness. EEG topography showed large
      increases in delta and theta activity, mainly evident at fronto-central areas.
      Standard MTs, as well as LTs and UTs, all increased as a consequence of SD. SICF
      also showed a significant increase as compared to pre-deprivation values, but
      only in females. The increase of theta activity was strongly associated in the
      left frontal and prefrontal cortex to a smaller decrease of corticospinal
      excitability, expressed by MTs, and a larger increase of intracortical
      facilitation, expressed by SICF. TMS and EEG measures converge in indicating that
      SD has severe effects on both cortical and corticospinal excitability, as shown
      respectively by the increases of slow-frequency EEG power and MTs. The SICF
      enhancement in females and the results of the combined topographical analysis of
      EEG and TMS changes are coherent with the hypothesis that cortical TMS-evoked
      responses are higher as a consequence of a longer wakefulness. However, the lack
      of an increase in cortical excitability after prolonged wakefulness in males
      suggests some caution in the generalization of these effects, that deserve
      further investigation.

PMID- 17524676
TI  - Tissue engineering and rotator cuff tendon healing.
AB  - Rotator cuff tears are common soft-tissue injuries that often require surgical
      treatment. Initial efforts to better tendon healing centered on improving the
      strength of the repair. More recent studies have focused on biologic enhancement
      of the healing process. Tissue engineering is a multidisciplinary field that
      involves the application of scientific principles toward creating living tissue
      to replace, repair, or augment diseased tissue. Gene therapy involves the
      transfer of a certain gene into a cell so that the cell translates the gene into
      a specific protein. The advantage of using a gene-therapy, tissue-engineered
      approach to effect healing rests in the ability of the physician to select growth
      factors with documented roles in the tendon-healing cascade. Ideally, an
      improvement to the current repair technique would yield improved tendon healing
      leading to improved clinical results.

PMID- 17524677
TI  - Structure of pericellular matrix around agarose-embedded chondrocytes.
AB  - OBJECTIVE: Determine whether the structure of the type VI collagen component of
      the chondrocyte pericellular matrix (PCM) generated by agarose-embedded
      chondrocytes in culture is similar to that found in native articular cartilage.
      METHODS: Confocal microscopy, quick-freeze deep-etch electron microscopy, and
      real-time polymerase chain reaction (PCR) were used to investigate temporal and
      spatial patterns of type VI collagen protein deposition and gene expression by
      bovine chondrocytes during 4 weeks of culture within a 2% agarose hydrogel.
      Similar analyses were performed on chondrocytes within samples of intact
      cartilage obtained from the same joint surfaces as those used for cell isolation
      for comparison. RESULTS: Type VI collagen accumulated uniformly around cells
      embedded in agarose, with the rate of deposition slowing after the second week.
      After 1 week, PCM fibrils were observed to be oriented perpendicular to the cell
      surface, in contrast with the primarily tangential fibrillar arrangement observed
      in native articular cartilage. Expression of col6 in agarose-embedded cells was
      initially much higher ( approximately 400%) than that in chondrocytes within
      cartilage. Expression of col6 in the cultured chondrocytes declined by
      approximately 60% after 1 week, and remained stable thereafter. CONCLUSIONS: PCM
      structure and composition around cells in a hydrogel scaffold may be different
      than that in native cartilage, with potential implications for mass transport,
      mechanotransduction, and ultimately, the success of tissue engineering
      approaches.

PMID- 17524678
TI  - Mesenchymal progenitor cells in adult human dental pulp and their ability to form
      bone when transplanted into immunocompromised mice.
AB  - The technique of tissue engineering is developing for the restoration of lost
      tissues. This new technique requires cells that fabricate tissue. Mesenchymal
      stem cells in bone marrow have been used as the cell source for this technique;
      however, dental pulp cells have recently been shown to possess stem-cell-like
      properties. We earlier demonstrated that dental pulp cells proliferate and
      produce an extracellular matrix that subsequently becomes mineralized in vitro.
      We now report that such dental pulp cells (first to eighth passage) produced bone
      instead of dentin when those cells were implanted into subcutaneous sites in
      immunocompromised mice with HA/TCP powder as their carrier. This evidence shows
      that dental pulp cells are the common progenitors of odontoblasts and
      osteoblasts, or dental pulp cells are mesenchymal stem cells themselves. It is
      expected that dental pulp cells can be a useful candidate cell source for tissue
      engineering, and contain the potential of new therapeutic approaches for the
      restoration of damaged or diseased tissue.

PMID- 17524679
TI  - Evaluation of angiogenesis in normal and lichen planus skin by CD34 protein
      immunohistochemistry: preliminary findings.
AB  - Angiogenesis is a critical component of both neoplastic and chronic inflammatory
      disorders, but whether angiogenesis also occurs in inflammatory skin diseases
      (such as lichen planus) has yet to be established. This study tests the
      hypothesis that the development of cutaneous lichen planus is associated with
      alterations of dermal vascularization (microvessel density, MVD). Thirty cases of
      cutaneous lichen planus and 40 cases of normal skin were studied. Dermal
      microvessels were immunostained for CD34 and counted in 10 areas with the highest
      numbers of microvessels; the mean value represented the final MVD. Compared with
      normal skin, dermal microvessel density was increased in cutaneous lichen planus
      [mean, 2.50 (SEM, 0.09) versus 1.39 (SEM, 0.12)]. The microvessel number was
      higher in the dermal inflammatory infiltrate (intralichenoid infiltrate) and at
      dermoepidermal junction (below Max-Josef space) compared with adventitial dermis
      [mean, 2.50 (SEM, 0.09) versus 1.6 (SEM, 0.10)]. The higher MVD values in
      cutaneous lichen planus suggest a possible link between angiogenesis, and
      development of these cutaneous lesions. These results provide a morphological
      evidence of potent angiogenic activity in cutaneous lichen planus, indicating
      that the local microvasculature may undergo an intense process of inflammation
      dependent angiogenesis.

PMID- 17524680
TI  - Venous reflux and venous distensibility in varicose and healthy veins.
AB  - OBJECTIVES: The aim of this study was to analyse venous diameter changes and
      venous reflux parameters, assessed during a standardised Valsalva manoeuvre in
      healthy subjects and in patients with varicose veins. METHODS: Measurements were
      carried out in 444 vein segments, (96 legs of 48 healthy volunteers, 52 legs of
      35 patients with varicose veins). The common femoral vein (CVF), the femoral vein
      (FV) and the great saphenous vein (GSV) were investigated. The parameters of
      reflux and the relative venous diameter change (VD diff %) were measured
      simultaneously during a standardised Valsalva manoeuvre. RESULTS: Venous diameter
      changes during Valsalva manoeuvre (VD diff) were significantly greater in the GSV
      and in the deep veins of varicose patients compared to healthy subjects. The
      median (Interquartile range) of VD max in the CFV was: 13.1 (3.5) mm and 11.2
      (3.4) mm (p=0.0002, Mann-Whitney - U test), in the FV 7.8 (2.7) mm and 6.9 (2.0)
      mm (p=0.01, Mann-Whitney), in the GSV: 7.3 (3.7) mm and 4.2 (1.1) mm (p<0.0001,
      Mann-Whitney) for the varicose and healthy veins respectively. Good correlation
      was seen for the retrograde peak reflux velocity (PRV) and VD diff % in varicose
      veins (r=0.71 (0.57 - 0.81) p<0.0001, Mann-Whitney). CONCLUSION: Relative venous
      diameter--changes during a standardised Valsalva manoeuvre are significantly
      larger in the deep and superficial veins of varicose vein patients compared with
      healthy veins, the increased distensibility correlates with venous reflux
      parameters in varicose vein patients.

PMID- 17524681
TI  - Surgical management of ameloblastoma in children.
AB  - OBJECTIVE: The purpose of this study was to report experience in the treatment of
      ameloblastoma in Taiwanese children and to discuss the treatment regimen. STUDY
      DESIGN: Fifteen patients, all younger than 18 years of age, with a diagnosis of
      ameloblastoma in our department between January 1991 and December 2004 were
      selected for study. Data included sex, age at surgery, tumor type, size and site
      of lesion, primary surgical methods, use of adjuvant therapy, complications,
      recurrences, and course of follow-up. RESULTS: Ages ranged from 9 to 17 (average
      was 13.7 years). Nine were male, 6 were female; the sex ratio was 1.5:1. Fourteen
      lesions were in the mandible (1 in the symphysis, 13 in the mandibular posterior
      area) and only 1 was in the maxilla. The size of the lesions ranged from 4 x 2.5
      cm to 8 x 8 cm. Clinical typing included 8 unicystic type, 3 multicystic type,
      and 4 solid types. Of the histologic types, 5 were plexiform, 3 were mixed type,
      and 3 were acanthomatous type. Complications included numbness of the lower lip
      and contour defect of the face. Three cases (20%) were recurrent, and 1 patient
      had 2 recurrences. CONCLUSIONS: Good results can be achieved in the treatment of
      ameloblastoma in children using conservative surgery. In the event of recurrence,
      a second surgery can be successful. Patient compliance and careful follow-up are
      important.

PMID- 17524682
TI  - Leakage of 4 resin-based root-canal sealers used with a single-cone technique.
AB  - OBJECTIVE: The aim of this study was to measure leakage of 4 resin-based sealers.
      STUDY DESIGN: Four groups of premolars (n = 60) were prepared using GT Rotary
      files and the crown-down technique and filled by the single-cone technique with
      AH26, AHPlus, EndoREZ, and an experimental MBP as sealer. Leakage was measured
      using the fluid filtration method after 15, 30, and 60 days and determined as
      microL/min(-1) x 10 psi. RESULTS: Statistical analysis by ANOVA and Tukey HSD
      test indicated that root fillings with AH Plus and the MBP showed lower leakage
      values after 15 days (P < .05). At 30 days, AH26 presented higher leakage values
      when compared to other sealers (P < .05). At 60 days, MBP and AH Plus presented
      the lower leakage values, differing significantly from EndoREZ (P < .05).
      CONCLUSION: It was observed that AH Plus and the experimental MBP showed lower
      leakage after 60 days than AH 26 and EndoREZ.

PMID- 17524683
TI  - Rare associations of dens invaginatus and mesiodens.
AB  - Dens invaginatus is a developmental variation resulting from an alteration in the
      normal growth pattern of the dental papilla. Synonyms of this disturbance include
      dens in dente, invaginated odontome, tooth inclusion, and dentoid in dente.
      Radiographically, it is observed as infolding of a radiopaque ribbon-like
      structure, with equal density as enamel, extending from the cingulum into the
      root canal and sometimes reaching the root apex, assigning the appearance of a
      small tooth within the coronal pulp cavity. This article presents 2 case reports.
      The first describes an 8-year-old girl with dens invaginatus in a mesiodens; the
      second report describes a 16-year-old boy presenting with 2 mesiodens, both
      associated with dens invaginatus.

PMID- 17524684
TI  - Somatic focus/awareness: Relationship to negative affect and pain in chronic pain
      patients.
AB  - Somatic focus refers to the tendency to notice and report physical symptoms, and
      has been investigated in relation to chronically painful conditions. This study
      investigated the relationship between somatic focus, as measured by the
      Pennebaker Inventory of Limbic Languidness (PILL), negative affect and pain. A
      secondary purpose of the present study was to examine sex differences in these
      relationships. Participants included 280 chronic pain patients (69.6% females,
      88.9% Caucasian), who completed a battery of self-report measures on somatic
      focus, pain, negative affect, coping, and dysfunction. Results for the overall
      sample revealed that the PILL shares considerable variance with measures of
      negative affect, particularly with the physiological components of anxiety and
      depression. When the results were analyzed separately for male and female
      patients, it was found that several components of negative affect and cognitive
      factors play a stronger role in predicting somatic focus among men compared to
      women. Additional analyses then examined whether somatic focus was predictive of
      male and female patients' pain reports. Results indicated that somatic focus
      explained a small, but unique amount of variance in female patients' pain
      reports, which differed from the relationship observed among male patients.

PMID- 17524685
TI  - Determination of chemical shift anisotropies of unresolved carbonyl sites by C
      alpha detection under magic-angle spinning.
AB  - We demonstrate that the static powder pattern line shape of chemical shift
      anisotropy (CSA) can be obtained for unresolved carbonyl sites of polypeptides
      under magic-angle spinning. The CSA interaction is first recoupled at the
      carbonyl site. The phase factors associated with the CSA recoupling are then
      transferred to the adjacent alpha carbon by an isotropic polarization transfer
      based on scalar spin-spin coupling. Because alpha carbons of polypeptides are
      usually better resolved, we can then obtain the CSA static powder pattern line
      shapes of the carbonyl sites after Fourier transformation in the second
      dimension. We validate our approach experimentally by measurements on [U-(13)C,
      (15)N]-l-alanine, [U-(13)C, (15)N]-l-valine and prion fibrils with uniform (13)C
      and (15)N labels on selected residues.

PMID- 17524686
TI  - A new decoupling method for accurate quantification of polyethylene copolymer
      composition and triad sequence distribution with 13C NMR.
AB  - (13)C NMR is a powerful analytical tool for characterizing polyethylene copolymer
      composition and sequence distribution. Accurate characterization of the
      composition and sequence distribution is critical for researchers in industry and
      academia. Some common composite pulse decoupling (CPD) sequences used in
      polyethylene copolymer (13)C NMR can lead to artifacts such as modulations of the
      decoupled (13)C NMR signals (decoupling sidebands) resulting in systematic errors
      in quantitative analysis. A new CPD method was developed, which suppresses
      decoupling sidebands below the limit of detection (less than 1:40,000 compared to
      the intensity of the decoupled signal). This new CPD sequence consists of an
      improved Waltz-16 CPD, implemented as a bilevel method. Compared with other
      conventional CPD programs this new decoupling method produced the cleanest (13)C
      NMR spectra for polyethylene copolymer composition and triad sequence
      distribution analyses.

PMID- 17524687
TI  - Low temperature probe for dynamic nuclear polarization and multiple-pulse solid
      state NMR.
AB  - Here, we describe the design and performance characteristics of a low temperature
      probe for dynamic nuclear polarization (DNP) experiments, which is compatible
      with demanding multiple-pulse experiments. The competing goals of a high-Q
      microwave cavity to achieve large DNP enhancements and a high efficiency NMR
      circuit for multiple-pulse control lead to inevitable engineering tradeoffs. We
      have designed two probes-one with a single-resonance RF circuit and a horn-mirror
      cavity configuration for the microwaves and a second with a double-resonance RF
      circuit and a double-horn cavity configuration. The advantage of the design is
      that the sample is in vacuum, the RF circuits are locally tuned, and the
      microwave resonator has a large internal volume that is compatible with the use
      of RF and gradient coils.

PMID- 17524688
TI  - Eosinophilic granuloma of the orbit: report of two cases.
AB  - We present clinical, radiological, and histopathological findings and treatment
      results of two infants with orbital eosinophilic granuloma. Both patients
      presented at 1 year of age with unilateral proptosis, periorbital edema, and a
      superotemporally located, ill-defined orbital mass on computed tomographic (CT)
      imaging, with bone erosion in one patient. After subtotal excision,
      histopathological examination revealed eosinophilic granuloma, and the proptosis
      resolved with no sign of orbital tumor recurrence or systemic involvement at 12
      and 23 months follow-up. Eosinophilic granuloma is a rare childhood orbital tumor
      that may or may not present with osteolytic change.

PMID- 17524689
TI  - Late-onset pediatric glaucoma associated with cutis marmorata telangiectatica
      congenita managed with Molteno implant surgery: case report and review of the
      literature.
AB  - Cutis marmorata telangiectatica congenita (CMTC) is characterized by the
      appearance of telangiectasia, phlebectasia, and a persistent reticular pattern of
      subcutaneous vasculature at or soon after birth. Up to 90% of cases are
      associated with systemic abnormalities, which include body asymmetry, cutaneous
      atrophy, neurological abnormalities, and vascular anomalies (nevus flammeus,
      Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and capillary and cavernous
      hemangiomas). Glaucoma is the most commonly reported ocular association of CMTC,
      usually presenting in infancy. We report a case of CMTC associated with the
      previously unreported onset of glaucoma in mid-childhood that was managed by
      glaucoma drainage implant surgery and review the literature on glaucoma
      associated with this condition.

PMID- 17524690
TI  - Exploring the active site of acyl homoserine lactones-dependent transcriptional
      regulators with bacterial quorum sensing modulators using molecular mechanics and
      docking studies.
AB  - A comparative molecular modelling study of acyl homoserine lactones-dependent
      transcriptional regulators (TraR, SdiA, LuxR and LasR) involved in bacterial
      quorum sensing (QS) revealed a high structural homology of their active site.
      Docking studies within the active site of TraR of fixed conformations obtained
      using molecular mechanics calculations showed that TraR, for which the
      crystalline structure is known, is a relevant model for the study of other
      protein-ligand interactions in the same protein family. Structure-activity
      relationships of AHLs derived QS modulators including carboxamides, sulfonamides
      and ureas were thus investigated. The results show that Tyr61, a residue
      conserved in the LuxR-proteins family, is involved in attractive interactions
      with aromatic carboxamide antagonists. Tyr53, Tyr61 and Asp70, conserved
      residues, are implicated in both the development of additional hydrogen bonds and
      attractive interactions with the N-sulfonyl homoserine lactones and AHLs derived
      ureas antagonists.

PMID- 17524691
TI  - Neuromuscular and phospholipase activities of venoms from three subspecies of
      Bothrops neuwiedi (B. n. goyazensis, B. n. paranaensis and B. n. diporus).
AB  - The Bothrops neuwiedi (Neuwied's lancehead) species complex consists of a variety
      of subspecies with a wide distribution in South America. In this work, we
      compared the neuromuscular blockade caused by venoms from three subspecies (B. n.
      goyazensis, B. n. paranaensis and B. n. diporus) of this complex using chick
      biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations and
      investigated their phospholipase A2 (PLA2) activities and electrophoretic
      profiles. The order of potency of PLA2 activity was B. n. diporus>B. n.
      paranaensis>B. n. goyazensis. In BC preparations, B. n. goyazensis venom (50
      microg/mL) was significantly (p<0.05) more active than B. n. paranaensis and B.
      n. diporus venoms, which did not produce a significant blockade at this time
      interval; after 120 min, B. n. goyazensis, B. n. paranaensis and B. n. diporus
      venoms (100 microg/mL) produced blockades of 57.4+/-5%, 30+/-3% and 17.4+/-7%
      (n=3-6 each), respectively. The three venoms inhibited contractures in response
      to ACh, indicating interference with postsynaptic neurotransmission. Only B. n.
      goyazensis and B. n. paranaensis venoms caused a long-lasting, concentration
      dependent muscle contracture prior to blockade. In PND preparations, all of the
      venoms blocked the twitch-tension responses within 45-100 min, indicating that
      these preparations were more sensitive than avian preparations. There was a
      correlation between PLA2 activity and the time for 50% blockade in PND but not in
      BC preparations. SDS-PAGE showed quantitative rather than qualitative differences
      among the venoms. These results indicate that the venoms of the three subspecies
      had similar profiles of neuromuscular activity, although the relationship with
      PLA2 activity varied with the preparation used.

PMID- 17524692
TI  - Annual, seasonal and individual variation in hematology and clinical blood
      chemistry profiles in bottlenose dolphins (Tursiops truncatus) from Sarasota Bay,
      Florida.
AB  - Hematology and clinical blood chemistry (HCBC) profiles in free-living bottlenose
      dolphins from Sarasota Bay, Florida have been monitored over a 14-year period.
      This long-term dataset includes samples from recaptured dolphins, enabling
      individual variation to be accounted for when investigating seasonal and annual
      variability. Four different laboratories carried out the assays and inter
      laboratory comparisons found significant differences in 31 of 39 parameters
      measured. However, variability in comparable HCBCs by sex, age, condition, season
      and year could be investigated. Significant relationships with the independent
      variables were found for the majority of the HCBCs. Notable consistent seasonal
      differences included significantly elevated glucose and significantly lower
      creatinine concentrations in winter compared to summer. These differences may be
      due to energetic or thermoregulatory fluctuations in the animals by season and do
      not necessarily have any clinical significance. Erythrocyte counts were
      significantly lower in the winter, possibly also due to nutritional differences.
      Albumin and calcium levels in this population have increased significantly over
      the years of monitoring and consistently across seasons, being higher in the
      winter than the summer. Again, nutritional and thermal constraints seem to be the
      most likely environmental factors influencing these patterns.

PMID- 17524693
TI  - Comparative study of myocardial high energy phosphate substrate content in slow
      and fast growing chicken and in chickens with heart failure and ascites.
AB  - In order to explain the biochemical mechanisms associated with deteriorating
      heart function in broiler chickens, this study compared myocardial high energy
      phosphate substrates in leghorns, feed restricted (Broilers-Res) broilers, ad
      libitum fed broilers (Broilers-AL), and in broilers that developed heart failure
      and ascites. The profile of adenine nucleotide content in the heart tissue did
      not differ between leghorns and Broilers-Res, but there were significant
      differences among Broilers-Res, Broilers-AL, and broilers with ascites. During
      intensive growth periods, leghorns and Broilers-Res showed increasing trends in
      heart ATP levels, whereas in fast growing broilers the heart ATP declined
      (p<0.021). ATP:ADP and ATP:CrP ratios increased with age in both leghorn and
      Broilers-Res, declined in fast growing broilers, and were the lowest in broilers
      that developed heart failure. The changes in heart high energy phosphate profile
      in broilers suggest that the energy demand of the heart during a rapid growth
      phase may exceed the bird's metabolic capacity to supply adequate levels of high
      energy phosphate substrate. The insufficiency of energy substrate likely
      contributes to the declining heart rate. In some individuals this may lead to
      impaired heart pump function, and in more severe cases may progress to heart pump
      failure.

PMID- 17524694
TI  - [Marketing in the world of blood donation].
AB  - Public and non-profit organizations have long debated how marketing concepts and
      management styles apply to their sector of activity as they are largely derived
      from principles of consumerism and economic decision-making proper to the private
      sector. The arrival of marketing in the world of blood donation is no exception.
      The purpose of this article is to illustrate concretely how marketing techniques
      can contribute in achieving the objectives of a blood donation program: a
      marketing model that is adapted to the realities of blood donation in Quebec.
      Although types of marketing are as varied as the fields they are used in, the
      major marketing activities of this program fall under positioning, operational or
      relationship marketing. The process is presented in the form of a cycle that
      includes four major phases containing all marketing functions, that is, raising
      public awareness, acquiring a clientele, client retention and loyalty building,
      and establishing the relationship. Finally, the information and effective
      management of information are at the heart of the marketing process. In fact,
      research, understanding our customers and their expectations, and measuring our
      performance are essential for the success of any marketing initiative.

PMID- 17524695
TI  - [Immunohematologic surveillance of the pregnant woman and the new prevention
      policy of anti-RH1 allo-immunization].
AB  - Despite the generalization of immunoprophylaxis by anti-RH immunoglobulins since
      1970 and improved management of at-risk pregnancies, allo-immunization due to the
      RH1 antigen (formerly known as Rhesus D or Rh D) remains widespread. In fact,
      anti-RH1 antibodies currently constitute over one-third of the immune antibodies
      detected after pregnancy. At the same time, allo-immunizations against others
      antigens than anti-RH1, especially anti-RH4 (anti-c) and anti-KEL1 (anti-Kell)
      increase. Allo-immunization, its follow-up during pregnancy, and its prevention
      are therefore still topical, and concern all the pregnant women.
      Immunohematological tests used in antenatal patients have gone a long way.
      However, despite a great deal of progress, we should not loose sight of the fact
      that these tests give only an indirect measurement and will only help the
      obstetrician, in conjunction with other fetal parameters to assess the severity
      of the haemolytic disease. The best method to assess the severity is the
      determination of the level of fetal hemoglobin after fetal blood sampling but
      this procedure is not without risk. Since 13 years, it is possible to determine
      the fetal RHD genotype of using amniocytes and to day directly with maternal
      plasma. All pregnant women should be blood-typed for ABO-RH-KEL1 and the blood
      tested for clinically irregular antibodies. The trend in anti-RH levels is more
      important than the level itself. Manual titration is simple but only provides
      rough, semiquantitative estimates of anti-RH concentration. Quantitative
      hemagglutination methods, using auto-analyzers and appropriate anti-RH1
      standards, measured in mug/ml, are sensitive, rapid and have acceptable intra
      laboratory reproducibility. RH:-1 women who are non-sensitized against RH1
      antigen during and at the end of their pregnancy with a RH1 child. RH prophylaxis
      includes targeted prophylaxis after feto-maternal hemorrhage and now routine
      antenatal RH prophylaxis at the 28th week of gestation. It has been necessary to
      synthesize the indications of RH prophylaxis and immunohematological tests to
      assure an efficient therapeutic prevention.

PMID- 17524696
TI  - [Introduction of platelet additive solutions in transfusion practice. Advantages,
      disadvantages and benefit for patients].
AB  - Platelet additive solutions (PAS) have been developed since the years 1980.
      However, decisive improvements have been made in the last five years, leading
      nowadays to several PAS available for transfusion practice. Few compounds are
      present in PAS, with the intention of controlling platelet metabolic alterations
      and activation that occur during storage: acetate, which is a substrate for the
      tricarboxylic acid cycle, enables to maintain oxidative metabolism, is present in
      all PAS; a buffer effect is required to prevent the progressive pH fall during
      storage, and is obtained either with sodium phosphate or gluconate; platelet
      activation is controlled by citrate, and in the latest PAS, by magnesium and
      potassium. It is important to note that whatever the PAS used, it is mandatory to
      maintain a final concentration of 20-40% of plasma, mainly in order to ensure
      glucose availability. The use of PAS leads to a more rationalized blood
      processing, as it provides an additional volume of plasma available for plasma
      fractionation, it contributes to standardization of blood components, and it is
      part of at least one pathogen reduction process. The expected benefit for patient
      is the reduction of adverse reactions related to plasma. There is already
      evidence that the incidence of allergic adverse reactions is reduced. In the case
      of other less frequent adverse reactions such as transfusion related acute lung
      injury (TRALI) or haemolytic reaction due to minor ABO incompatibility, only a
      long-term follow-up through haemovigilance organization will be informative.

PMID- 17524697
TI  - [Training, skill and competences' follow-up].
AB  - Blood transfusion safety is a public health requirement, which is claimed by
      public health authorities and blood users too. In order to comply with
      transfusion safety, available national regulatory requirements must be strictly
      followed (or applied) by blood transfusion workers, caring nurses and physicians.
      Transfusion's good practices are based on knowledge of the process and the skill
      in blood transfusion fields. Quality systems, risks management, audits,
      inspections and certification programs implemented by blood establishments and
      patients' care services should lead to efficiency. All professionals involved in
      blood banking and transfusion processes (blood donation, preparation and storage
      of blood products, transfusion therapy...) must be qualified. They have to follow
      a program of continued training education. Their competence or ability must also
      be periodically assessed and documented to let continue and perform tasks safely.

PMID- 17524698
TI  - [Results of a 5 years follow-up of Arpe prosthesis for the basal thumb
      osteoarthritis].
AB  - INTRODUCTION: The surgical gold standart treatment of the thumb osteoarthritis is
      the trapeziectomy with tendon interposition with ligament reconstruction. The
      trapeziometacarpal prosthesis is insufficiently assessed in literature. METHODS:
      Between 1994 and 2001, 43 trapeziometacarpal prosthesis Arpe were implanted by
      the same surgeon for isolated trapeziometacarpal degenerative osteoarthritis. The
      minimum follow-up is 5 years. 33 women and 2 men , average age 59,4-years, were
      operated after failure of conservative treatment. 7 patients were lost sight of
      (9 prosthesis) and 2 deaths (2 prosthesis). 26 other patients (32 prostheses)
      were examined by the author with an original revision questionnaire associated to
      the score of DASH. RESULTS: 7 revisions were necessary: 5 for loosening, 1 for
      premature dismemberment and 1 for recurrent partial dislocation. The survival of
      the prosthesis is 85% in 5 years. In the group of 25 prosthesis still implanted,
      there is no radiological sign of loosening, but in some cases a development of
      medial ossification. The average DASH score is 27,4/100. All the patients of this
      group are satisfied or very satisfied. CONCLUSION: The prosthesis Arpe is an
      effective option in this series for the treatment of the degenerative
      trapeziometacarpal arthritis but its radioclinical control is necessary for the
      first year.

PMID- 17524699
TI  - [Against planned cesarean delivery in twin gestations].

PMID- 17524700
TI  - Fluid pressure driven fibril reinforcement in creep and relaxation tests of
      articular cartilage.
AB  - Biological tissues exhibit diverse mechanical behaviors because of complex
      material properties. As has been shown for ligaments and intervertebral discs,
      mathematical models often appear to well predict load responses individually by
      adjusting model parameters, but likely fail to describe several different load
      responses simultaneously using the same model parameters. In the present study,
      we attempted to describe and explain both creep and relaxation responses of
      articular cartilage using a fibril-reinforced model, which has been successfully
      used to account for the load response of the relaxation tests of articular
      cartilage. Experiments were performed on bovine articular cartilage disks (n=8)
      using multi-step loading protocols, involving both creep and relaxation in each
      protocol. The experimental results indicated that mechanical changes, such as
      fiber recruitment in collagen network during stretch, recovered fully upon
      unloading. Creep loading did not affect relaxation properties, and vice versa.
      Relaxation proceeded much faster than creep, because of different fluid pressure
      profiles. The load sharing among the proteoglycan matrix, collagen network and
      fluid pressurization was predicted to differ for the creep and relaxation
      testing. The experimentally observed strong creep and relaxation responses in
      unconfined compression could not be predicted if either fibril reinforcement or
      fluid pressurization were neglected. It was essential to consider the interplay
      between nonlinear fibril reinforcement and fluid pressurization for the transient
      response (this interplay may be best termed as fluid pressure driven fibril
      reinforcement). Fibril reinforcement played a relatively insignificant role in
      the compressive load response at equilibrium, in agreement with previous findings
      for cartilage stress relaxation testing.

PMID- 17524701
TI  - Optimization of 360 degrees projection fluorescence molecular tomography.
AB  - Fluorescence tomography of tissues has been generally limited to systems that
      require fixed geometries or measurements employing fibers. Certain technological
      advances however, have more recently allowed the development of complete
      projection 360 degrees tomographic approaches using non-contact detection and
      illumination. Employing multiple illumination projections and CCD cameras as
      detection devices vastly increases the information content acquired, posing non
      trivial computational and experimental requirements. In this paper, we use
      singular-value analysis to optimize experimental parameters relevant to the
      design and operation of emerging 360 degrees fluorescence molecular tomography
      (FMT) methods and systems for small animal imaging. We present the theoretical
      and experimental methodology, optimization results and their experimental
      validation. We further discuss how these results can be employed to improve the
      performance of existing FMT systems and guide the design of new systems.

PMID- 17524702
TI  - Validation of vessel-based registration for correction of brain shift.
AB  - The displacement and deformation of brain tissue is a major source of error in
      image-guided neurosurgery systems. We have designed and implemented a method to
      detect and correct brain shift using pre-operative MR images and intraoperative
      Doppler ultrasound data and present its validation with both real and simulated
      data. The algorithm uses segmented vessels from both modalities, and estimates
      the deformation using a modified version of the iterative closest point (ICP)
      algorithm. We use the least trimmed squares (LTS) to reduce the number of
      outliers in the point matching procedure. These points are used to drive a thin
      plate spline transform to achieve non-linear registration. Validation was
      completed in two parts. First, the technique was tested and validated using
      realistic simulations where the results were compared to the known deformation.
      The registration technique recovered 75% of the deformation in the region of
      interest accounting for deformations as large as 20 mm. Second, we performed a
      PVA-cryogel phantom study where both MR and ultrasound images of the phantom were
      obtained for three different deformations. The registration results based on MR
      data were used as a gold standard to evaluate the performance of the ultrasound
      based registration. On average, deformations of 7.5 mm magnitude were corrected
      to within 1.6 mm for the ultrasound based registration and 1.07 mm for the MR
      based registration.

PMID- 17524706
TI  - Looking back to move forward.

PMID- 17524707
TI  - Sifting through the research on supplements.

PMID- 17524708
TI  - Are all lawyers the same?

PMID- 17524709
TI  - Applying motivational enhancement to diverse populations.

PMID- 17524710
TI  - What we need to know about teen food habits and why.

PMID- 17524711
TI  - Regular sugar-sweetened beverage consumption between meals increases risk of
      overweight among preschool-aged children.
AB  - OBJECTIVE: To examine the relationship between consumption of sugar-sweetened
      beverages (eg, nondiet carbonated drinks and fruit drinks) and the prevalence of
      overweight among preschool-aged children living in Canada. DESIGN: Data come from
      the Longitudinal Study of Child Development in Quebec (1998-2002).
      SUBJECTS/SETTING: A representative sample (n=2,103) of children born in 1998 in
      Quebec, Canada. A total of 1,944 children (still representative of the same-age
      children in this population) remaining at 4 to 5 years in 2002 participated in
      the nutrition study. STATISTICAL ANALYSES PERFORMED: Data were collected via 24
      hour dietary recall interview. Frequency of sugar-sweetened beverage consumption
      between meals at age 2.5, 3.5, and 4.5 years was recorded and children's height
      and weight were measured. Multivariate regression analysis was done with
      Statistical Analysis System software. Weighted data were adjusted for within
      child variability and significance level was set at 5%. RESULTS: Overall, 6.9% of
      children who were nonconsumers of sugar-sweetened beverages between meals between
      the ages of 2.5 to 4.5 years were overweight at 4.5 years, compared to 15.4% of
      regular consumers (four to six times or more per week) at ages 2.5 years, 3.5
      years, and 4.5 years. According to multivariate analysis, sugar-sweetened
      beverage consumption between meals more than doubles the odds of being overweight
      when other important factors are considered in multivariate analysis. Children
      from families with insufficient income who consume sugar-sweetened beverages
      regularly between the ages of 2.5 and 4.5 years are more than three times more
      likely to be overweight at age 4.5 years compared to nonconsuming children from
      sufficient income households. CONCLUSIONS: Regular sugar-sweetened beverage
      consumption between meals may put some young children at a greater risk for
      overweight. Parents should limit the quantity of sweetened beverages consumed
      during preschool years because it may increase propensity to gain weight.

PMID- 17524713
TI  - Food and weight-related patterns and behaviors of Hmong adolescents.
AB  - OBJECTIVE: Little is known about the food and weight-related behaviors of Hmong
      adolescents. This study assessed these behaviors in Hmong adolescents and
      determined if they differed between Hmong and white teens or by country of birth.
      DESIGN: School-based cross-sectional study. SUBJECTS/SETTING: Hmong (n=649) and
      white (n=2,260) adolescents from 31 public middle and high schools in the
      Minneapolis/St Paul, MN, metropolitan area who participated in Project EAT
      (Eating Among Teens). MAIN OUTCOME MEASURES: Family meals, grocery shopping, and
      meal preparation; consumption of breakfast, snacks, and fast foods, physical
      activity and inactivity; body satisfaction, weight concern, body mass index, and
      weight-control behaviors. STATISTICAL ANALYSES PERFORMED: Variables were compared
      across race/ethnicity and by country of birth using chi(2) tests and general
      linear model regression. RESULTS: Hmong students reported greater participation
      in family meals and more involvement with food purchasing and preparation. Fast
      food consumption was similar among groups. Hmong teens reported less frequent
      breakfast consumption. The prevalence of overweight was higher in Hmong male
      adolescents than white male adolescents, but similar among female adolescents.
      Hmong students reported higher levels of weight concern, body dissatisfaction,
      dieting, unhealthful weight-control behaviors, less physical activity, and more
      inactivity than white students. Hmong male adolescents participated in extreme
      unhealthful weight-control behaviors four times more often than white male
      adolescents. CONCLUSIONS: Hmong adolescents appear to be at increased risk for
      obesity, body dissatisfaction, and unhealthful weight-control behaviors compared
      to white adolescents. There is a need for culturally tailored interventions to
      address these nutrition and weight issues among Hmong adolescents.

PMID- 17524714
TI  - Chronic diseases and dietary changes in relation to Korean Americans' length of
      residence in the United States.
AB  - BACKGROUND: National health in the United States is influenced by the dietary
      norms brought into the country by an increasing number of immigrants. OBJECTIVES:
      This cross-sectional study aimed to document dietary changes and disease
      prevalence in relation to the length of residence in the United States for Korean
      Americans in Michigan. DESIGN: Of 1,860 questionnaires mailed out, 637 (34.3%)
      were returned with respondent-reported information, including demographics,
      weight and height, chronic diseases, and dietary patterns. SUBJECTS/SETTING:
      Included in the final analyses were 497 first-generation Korean-American
      immigrants (263 men, 234 women, aged 30 to 87 years). STATISTICAL ANALYSES
      PERFORMED: Analysis of covariance with the Tukey test and logistic regression
      models provided sex-specific analysis of dietary changes and disease patterns.
      All statistical analyses were adjusted for age. RESULTS: Chronic diseases
      reported most frequently by men and women, respectively, were hypertension,
      digestive diseases, arthritis, and diabetes. Length of residence in the United
      States (<or=15 years, 16 to 25 years, or >or=26 years) was inversely associated
      with the prevalence of digestive diseases in men (P=0.017) and women (P=0.001),
      and positively with respiratory diseases in men and thyroid disease in women
      (P<0.05). Length of residence in the United States was inversely associated with
      intake of rice/rice dishes in both men (servings per week, P<0.001) and women
      (P=0.012). The prevalence of digestive diseases associated inversely with length
      of residence and positively with servings of rice/rice dishes consumed for Korean
      American men. The age-adjusted odds ratio for digestive diseases was highest
      among men who had the shortest length of residence in the United States (<or=15
      years) and greater consumption of rice/rice dishes (>2 servings per day) (odds
      ratio 12.10; P=0.03). CONCLUSIONS: Dietary changes of Korean-American immigrants
      in the United States over time were associated with changes in their chronic
      disease patterns. These findings may help food and nutrition professionals who
      work with minority immigrants because they identify factors that affect changes
      in dietary patterns and work toward preventing diet-related diseases. Prospective
      studies could address underlying mechanisms of the observed diet-disease
      relationship with subsequent generations of Korean Americans, as well as various
      ethnic minority immigrants in the United States.

PMID- 17524715
TI  - Nutritional concerns in aboriginal children are similar to those in non
      aboriginal children in Prince Edward Island, Canada.
AB  - OBJECTIVE: To assess food consumption among aboriginal children living on Mi'kmaq
      reserves in Prince Edward Island, Canada. DESIGN: Data were collected as part of
      a larger study of health perceptions and behaviors in Mi'kmaq children and youth
      ages 1 to 18 years. Food consumption was assessed using a self-administered food
      frequency questionnaire during an in-home interview. SUBJECTS/SETTING: Fifty-five
      children living on a reserve (53% of total population) ages 9 to 18 years.
      STATISTICAL ANALYSES PERFORMED: The number of servings of milk products,
      vegetables and fruit, and snack foods/beverages was calculated by adding the
      responses to the frequency of consumption of foods assessed in each group. chi(2)
      analysis was used to assess differences in food consumption according to sex and
      age. RESULTS: Only one child reported consuming the recommended minimum of five
      vegetables and fruit daily (Canada's Food Guide to Healthy Eating, 1992) (mean
      [+/-standard deviation]=2.8+/-1.1 servings). Twenty-five (49%) of the children
      consumed three or more servings of milk products daily (mean=2.6+/-1.3 servings).
      Approximately half of the children had three or more snack foods/beverages daily
      (mean=3.1+/-2.2 servings). Younger children (grades 4 to 6) consumed more cereal,
      peanut butter, and yogurt than older children. There were no significant
      differences in food consumption between boys and girls. CONCLUSIONS: Our findings
      are consistent with past reports in aboriginal children. However, except for
      higher consumption of french fries, results are similar to recent surveys of
      other Prince Edward Island school children, suggesting a province-wide rather
      than cultural health issue.

PMID- 17524716
TI  - Dietary patterns of adolescent girls in Hawaii over a 2-year period.
AB  - OBJECTIVE: To describe changes in dietary patterns of adolescent girls in Hawaii
      from 2001 to 2003. DESIGN: Cohort study, with exams 2 years apart.
      SUBJECTS/SETTING: One hundred fifty-one girls of Asian, white, and mixed
      ethnicity who were aged 9 to 14 years at exam 1 and aged 11 to 16 years at exam 2
      and lived on the island of Oahu, HI. METHODS: Three-day diet records were
      obtained at each exam. Mean nutrient and food group intakes and weight, height,
      and body mass index were determined and compared between the two exams.
      STATISTICAL ANALYSES: Data are summarized as means+/-standard deviation unless
      otherwise stated. Differences in values between groups were analyzed for
      significance using paired t tests and multiple regression. RESULTS: Girls at
      exams 1 and 2 had mean carbohydrate intakes of 233 g and 241 g, respectively, and
      protein intakes of 67 g and 65 g, respectively. None of the carbohydrate intakes
      were below the Estimated Average Requirement (EAR) at exam 1 and only one girl
      was below at exam 2. Three percent of girls had protein intakes that were below
      the EAR at exam 1 whereas 9% were below at exam 2. For iron intakes, 3% of girls
      were below the EAR at exam 1 and 14% of girls were below at exam 2. Girls at
      exams 1 and 2 had mean calcium intakes of 733 mg and 732 mg, respectively, and
      fiber intakes of 11.2 g and 11.4 g, respectively; lower than the Adequate Intake
      recommendation. The percentage of energy from macronutrients in exams 1 and 2,
      respectively, was in range of the Appropriate Macronutrient Distribution Range
      for more than 70% of girls (76% for exam 1, 79% for exam 2), but the mean
      percentage intake of saturated fat intake was higher than the recommended range
      for more than 65% of the girls at both exams 1 and 2 (69% at exam 1, 73% at exam
      2). However, no significant differences were found in percent contribution of or
      in total intake of macronutrients between the two exams. More than half of girls
      (51% to 100%) did not consume the recommended number of Food Guide Pyramid
      Servings for any food group at either exam 1 or 2. A significant increase was
      found for sweetened carbonated beverage intake (from 130 g to 179 g; P<0.05) and
      for added sugar intake (from 16 tsp to 18 tsp; P<0.01) between exams 1 and 2, a
      level well above recommendations. As expected, mean body weight and mean body
      mass index increased significantly between exams 1 and 2 (P<0.05). CONCLUSIONS:
      These data suggest high dietary intakes of dietary fat and sugar, and increasing
      intakes of sweetened carbonated beverages and other high-sugar drinks during
      adolescence among girls in Hawaii.

PMID- 17524717
TI  - Promotion of physical activity in low-income mothers using pedometers.
AB  - OBJECTIVE: This study tested the effectiveness of a pedometer program for
      increasing physical activity levels and reducing body weight in overweight and
      obese mothers of young children. DESIGN: Participants' motivational readiness to
      exercise, exercise self-efficacy, pedometer steps, pedometer kilocalories, and
      anthropometrics were evaluated at week 0 and week 8; anthropometrics were
      reassessed at week 24. Healthful-weight mothers provided comparison data at
      baseline. SUBJECTS/SETTING: A convenience sample of 93 intervention women (body
      mass index [calculated as kg/m(2)] >or=25) and 31 comparison women (body mass
      index <25) were recruited from public health clinics, community centers, and
      churches. Eligibility criteria included Hispanic, African-American, or white
      ethnicity and low income (<200% of the federal poverty index). INTERVENTION: An 8
      week physical activity and dietary program was conducted. MAIN OUTCOME MEASURES:
      Motivational readiness to exercise, exercise self-efficacy, pedometer steps, and
      weight loss. STATISTICAL ANALYSES PERFORMED: Independent sample t tests, chi(2)
      tests, paired t tests, Wilcoxon signed-ranks tests, repeated measures analysis of
      variance, and Pearson and Spearman correlations. RESULTS: Mothers enhanced their
      motivational readiness to exercise, exercise self-efficacy, pedometer steps, and
      pedometer kilocalories. Reductions in body weight, percent body fat, and waist
      circumference also were observed. Significant correlations were found between
      exercise self-efficacy and exercise readiness (r=0.28, P<0.01), pedometer steps
      (r=0.30, P<0.01), and pedometer kilocalories (r=0.28, P<0.05). CONCLUSIONS: This
      intervention successfully increased the physical activity levels and promoted
      weight loss in low-income mothers. Public health clinics may wish to incorporate
      elements of this intervention into their programs to improve the physical fitness
      of recipients.

PMID- 17524718
TI  - Assessing dietary intake of drug-abusing Hispanic adults with and without human
      immunodeficiency virus infection.
AB  - OBJECTIVE: Drug abuse is an important risk factor for the human immunodeficiency
      virus (HIV) among Hispanics living in the northeastern United States, and both
      drug abuse and HIV are associated with nutritional deficiencies. The selection of
      a dietary assessment method most appropriate for Hispanic adults with/without HIV
      infection who may be drug abusers remains unclear. DESIGN: Participants were
      recruited into one of the three groups: HIV-infected drug abusers, HIV
      noninfected drug abusers, and HIV-infected non-drug abusers. Subjects who
      completed two of the three dietary methods were included in cross-sectional
      pairwise comparisons. SETTING: The baseline data from a prospective cohort study
      of the role of drug abuse in HIV/acquired immunodeficiency syndrome-related
      weight loss. RESULTS: The 286 enrolled participants completed 282 food frequency
      questionnaires (FFQs), 142 3-day diet records, and 270 24-hour recalls. Energy
      adjusted and deattenuated correlations between the FFQ and 3-day diet records
      ranged from 0.11 (carbohydrate) to 0.75 (caffeine). Twenty-seven of 33 nutrient
      intakes estimated by 3-day diet record were significantly lower than by FFQ
      (P<0.05). Three-day diet records underestimated dietary intake relative to the
      FFQ and 24-hour recall methods. Fifty percent of records were not completed.
      Energy estimates from the FFQ and 24-hour recall were similar to each other.
      CONCLUSIONS: The 24-hour recall gave higher mean dietary intake estimates, but
      would require multiple contacts with this difficult-to-reach population. The FFQ
      that was specifically designed for this Hispanic population performed well
      relative to the other methods.

PMID- 17524719
TI  - The association between food patterns and the metabolic syndrome using principal
      components analysis: The ATTICA Study.
AB  - BACKGROUND: Dietary habits have been associated with the prevalence of the
      metabolic syndrome. OBJECTIVE: The associations between foods or food patterns
      and the characteristics of the metabolic syndrome were evaluated. DESIGN: Cross
      sectional survey. SUBJECTS: During 2001 to 2002, 1,514 men (aged 18 to 87 years)
      and 1,528 women (aged 18 to 89 years) without any clinical evidence of
      cardiovascular disease were randomly enrolled, from the Attica region in Greece.
      MAIN OUTCOME MEASURES: Dietary habits were evaluated using a semiquantitative,
      food frequency questionnaire. Characteristics of the metabolic syndrome (ie,
      blood pressure, waist circumference, glucose, triglycerides, and high-density
      lipoprotein cholesterol) were also measured. STATISTICAL ANALYSIS: Principal
      components analysis was applied to extract dietary patterns from 22 foods or food
      groups. Multivariate regression analysis evaluated the associations between the
      extracted dietary patterns and characteristics of the metabolic syndrome.
      RESULTS: Six components were derived explaining 56% of the total variation in
      intake. Component 1 was characterized by the consumption of cereals, fish,
      legumes, vegetables, and fruits (explained variation 19.7%); component 2 was
      characterized by the intake of potatoes and meat (explained variation 11.7%),
      component 6 was characterized by alcohol intake (explained variation 4.8%),
      whereas the other components were mainly characterized by consumption of dairy
      and sweets. After adjusting for various confounders, component 1 was inversely
      associated with waist circumference, systolic blood pressure, triglycerides,
      positively associated with high-density lipoprotein cholesterol levels, and
      inversely with the likelihood of the metabolic syndrome (odds ratio [OR] 0.87,
      95% confidence interval [CI] 0.79 to 0.97), whereas components 2 and 6 were
      positively correlated with the previous indexes, and the likelihood of having the
      metabolic syndrome (OR 1.13, 95% CI 1.05 to 1.21 and OR 1.26, 95% CI 1.21 to
      1.33). CONCLUSIONS: A dietary pattern that includes cereals, fish, legumes,
      vegetables, and fruits was independently associated with reduced levels of
      clinical and biological markers linked to the metabolic syndrome, whereas meat
      and alcohol intake showed the opposite results.

PMID- 17524720
TI  - Do data support nutrition support? Part I: intravenous nutrition.
AB  - Intravenous (parenteral) nutrition has been advocated widely as adjunctive care
      in patients with a variety of underlying diseases. However, the enthusiasm for
      this therapeutic intervention was based largely on expert opinion. Because the
      best way to assess the efficacy of any treatment is to test it in a randomized
      controlled trial, this review will focus on data that was derived from such
      studies. Using established search strategies, randomized controlled trials were
      sought that compared one of two forms of intravenous nutrition: parenteral
      nutrition (nitrogen and >or=10 kcal/kg/day of non-protein calories for >or=5
      days) or protein-sparing therapy (nitrogen and fewer non-protein calories) with
      no type of artificial nutrition beyond regular food and/or standard (5%)
      dextrose. The randomized controlled trials were stratified by the underlying
      disease state. The clinical outcomes of interest were mortality, morbidity
      (total/infectious complications), and/or duration of hospitalization. More than
      100 randomized controlled trials failed for the most part to demonstrate that
      intravenous nutrition had any effect on clinical outcome. There were a few
      exceptions. In patients undergoing attempted curative surgery for upper
      gastrointestinal cancer, the use of preoperative parenteral nutrition seemed to
      reduce the incidence of major postoperative complications. However, this benefit
      was only found in low-quality randomized controlled trials. Findings conflict
      regarding the use of parenteral nutrition in patients with acute pancreatitis or
      undergoing bone marrow transplantation. Parenteral nutrition was harmful when
      provided to patients undergoing radiation or chemotherapy for cancer. Although no
      randomized controlled trials exist, it is assumed that parenteral nutrition is
      useful in patients with an inadequate gastrointestinal tract ("short gut"). Thus,
      for the most part, randomized controlled trials comparing intravenous nutrition
      to no artificial nutrition have not shown that this medical intervention is of
      benefit.

PMID- 17524721
TI  - Formative research of a quick list for an automated self-administered 24-hour
      dietary recall.
AB  - Twenty-four-hour dietary recalls are used to collect high-quality dietary data.
      Because they require highly trained interviewers, recalls are expensive and
      impractical for large-scale nutrition research, leading to the use of food
      frequency questionnaires. We are developing a computer-based, self-administered
      24-hour dietary recall for use by adults. Our goal is an easy-to-use, low-cost,
      publicly available, Web-enabled instrument that will include elements of the
      Automated Multiple Pass Method developed by the US Department of Agriculture,
      which uses five passes to enhance recall. The initial pass is called the "quick
      list" and allows respondents to report foods consumed the previous day freely, in
      any order, and without detail. Using a crossover design, we conducted initial
      formative pilot testing among 18 adults in a self-administered computer
      environment. We tested two versions of a "quick list" (the first Automated
      Multiple Pass Method pass) for remembering foods consumed the previous day:
      "unstructured" and "meal-based." Respondents showed a strong preference for the
      meal-based version (13 of 18), although positive features of both were
      identified. Chronological reporting was most common, although many foods were
      sporadically reported out of order. Versions did not appreciably differ in number
      of foods reported, moved, or deleted. Usability issues and preferences were also
      identified. If these developmental efforts prove successful, the use of
      affordable automated recalls could be valuable in clarifying diet-disease
      associations in observational epidemiologic studies and measuring dietary
      compliance in clinical trials. This pilot work illustrates the usefulness of
      formative cognitive and usability testing for questionnaire and software
      development.

PMID- 17524722
TI  - An exploratory investigation of dietary intake and weight in human
      immunodeficiency virus-seropositive individuals in Accra, Ghana.
AB  - In Africa, the human immunodeficiency virus and acquired immunodeficiency
      syndrome (HIV/AIDS) complex is commonly referred to as "slim disease" because, as
      the disease progresses, food intake and metabolism are altered, leading to
      visible body weight loss. In this descriptive, cross-sectional pilot study, 50
      HIV-seropositive adults attending the Korle Bu Teaching Hospital in Accra, Ghana,
      were interviewed during the late spring of 2003. Demographics, medical HIV
      history and current status of their HIV disease, food safety, and food security
      information were collected. One 24-hour dietary recall was completed, height and
      weight were measured, and body mass index (BMI) was calculated for each
      participant. Results show that women participants had a higher mean BMI and
      maintained it through disease progression compared with men (P<0.02). The
      majority of the participants cited cost as a barrier in purchasing adequate
      amounts of food (92%). Fruit and vegetable intake was low overall (<three
      servings/day). The foods contributing most to daily energy intake were fried
      fish, white rice, kenkey, white bread, and fufu. In fighting the global HIV/AIDS
      epidemic, registered dietitians must consider barriers to achieving optimal
      nutritional status in a cultural context to enhance feasibility and ensure the
      effectiveness of dietary interventions.

PMID- 17524723
TI  - Nutrient intake of children with intractable epilepsy compared with healthy
      children.
AB  - Growth retardation is common among children with epilepsy, and poor dietary
      intake may be one of the causes. The goal of this cross-sectional study was to
      compare the nutrient intake of children 1 to 8 years of age with intractable
      epilepsy to healthy children of the same age from the National Health and
      Nutrition Examination Survey 2001 to 2002 (N=1,718) and with the Dietary
      Reference Intakes. Children with intractable epilepsy were divided into two age
      groups: 1.0 to 3.9 and 4.0 to 8.9 years, to correspond with the Dietary Reference
      Intakes. Forty-three children with intractable epilepsy, mean age=4.7+/-2.2
      years, had significantly lower intakes (P<0.05) of total energy; protein;
      carbohydrate; fat; dietary fiber; vitamins A, E, B-6, and B-12; riboflavin;
      niacin; folate; calcium; phosphorus; magnesium; zinc; copper; and selenium
      compared with healthy children. Thirty percent or more of the children with
      intractable epilepsy in both age groups had intakes below the Recommended Dietary
      Allowance or Adequate Intake for vitamins D, E, and K; folate; calcium; linoleic
      acid; and alpha-linolenic acid. Health care professionals caring for children
      with intractable epilepsy should be aware of this pattern of decreased nutrient
      intake and educate families to provide an adequate diet and/or consider
      vitamin/mineral supplementation.

PMID- 17524724
TI  - Fruits and vegetables taken can serve as a proxy measure for amounts eaten in a
      school lunch.
AB  - This study tests the hypothesis that fruits and vegetables taken on students'
      lunch trays are usable proxies for fruits and vegetables eaten, and that the
      proxy is useful with children in the youngest school grade (ie, grade 1; ages 6
      to 8 years). A total of 1,168 randomly selected students in grade 1 and grade 3
      (ages 8 to 10 years) in 26 schools in the Twin Cities, MN, metropolitan area were
      observed before and after an intervention that was applied to 13 randomly
      selected schools. Trained observers recorded food quantities on a child's tray
      and measured food consumed during the meal. Correlations between amounts of
      fruits and vegetables taken and eaten ranged from 0.74 to 0.96. The median
      correlation in grade 1 was the same, 0.82, as in the combined sample. Food taken
      and food eaten as alternative response variables resulted in the same conclusions
      about the effects of intervention. The hypothesis is strengthened that food taken
      can be used as a proxy for consumption in future nutrition education research.

PMID- 17524725
TI  - Development of a polyamine database for assessing dietary intake.
AB  - Reducing the concentration of polyamines (spermine, spermidine, and putrescine)
      in the body pool may slow the cancer process. Because dietary spermine,
      spermidine, and putrescine contribute to the body pool of polyamines, quantifying
      them in the diet is important. Limited information about polyamine content of
      food is available, especially for diets in the United States. This brief report
      describes the development of a polyamine database linked to the Fred Hutchinson
      Cancer Center food frequency questionnaire (FFQ). Values for spermine,
      spermidine, and putrescine were calculated and reported per serving size
      (nmol/serving). Of the foods from the database that were evaluated, fresh and
      frozen corn contain the highest levels of putrescine (560,000 nmol/serving and
      902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111
      nmol/serving), and green pea soup contains the highest concentration of spermine
      (36,988 nmol/serving). The polyamine database and FFQ were tested with a
      convenience sample (n=165). Average daily polyamine intakes from the sample were:
      159,133 nmol/day putrescine, 54,697 nmol/day spermidine, and 35,698 nmol/day
      spermine. Orange and grapefruit juices contributed the greatest amount of
      putrescine (44,441 nmol/day) to the diet. Green peas contributed the greatest
      amount of spermidine (3,283 nmol/day) and ground meat contributed the greatest
      amount of spermine (2,186 nmol/day). Development of this database linked to an
      FFQ provides a means of estimating polyamine intake and contributes to
      investigations relating polyamines to cancer.

PMID- 17524726
TI  - Low-energy-density diets are associated with higher diet quality and higher diet
      costs in French adults.
AB  - Low-energy-density diets are often recommended for weight control. Such diets
      have a higher nutrient content than do high-energy-density diets. This study
      tested the hypothesis that energy-dense diets have a relatively low monetary
      cost, whereas less energy-dense diets are more expensive. In this cross-sectional
      study, dietary intakes of 1,474 French adults (672 men, 802 women), aged 15 to 92
      years, were assessed using 7-day diet records. Dietary energy density (kcal/g)
      was calculated by dividing total dietary energy by the edible weight of foods and
      caloric beverages consumed. Diet cost ($/7 days or $/2,000 kcal) was estimated
      using mean national food prices for 895 foods. The relationship between dietary
      energy density and diet cost was examined in a linear regression model. Within
      each quintile of energy intakes, the more energy-dense diets were associated with
      lower diet quality and with lower diet costs (r(2)=0.38 to 0.44). In a regression
      model, the more energy-dense diets cost less, whereas low-energy-density diets
      cost substantially more, adjusting for energy intakes, sex, and age. The finding
      that energy-dense diets cost less per 2,000 kcal may help explain why the highest
      rates of obesity are observed among groups of limited economic means. The finding
      that low-energy-density diets are associated with higher diet costs suggests that
      lasting improvements in diet quality may require economic as well as behavioral
      interventions.

PMID- 17524727
TI  - Where can I find resources to assist my client with meal planning?

PMID- 17524728
TI  - The interdependence between screening methods and screening libraries.
AB  - The most common methods for discovery of chemical compounds capable of
      manipulating biological function involves some form of screening. The success of
      such screens is highly dependent on the chemical materials - commonly referred to
      as libraries - that are assayed. Classic methods for the design of screening
      libraries have depended on knowledge of target structure and relevant
      pharmacophores for target focus, and on simple count-based measures to assess
      other properties. The recent proliferation of two novel screening paradigms,
      structure-based screening and high-content screening, prompts a profound rethink
      about the ideal composition of small-molecule screening libraries. We suggest
      that currently utilized libraries are not optimal for addressing new targets by
      high-throughput screening, or complex phenotypes by high-content screening.

PMID- 17524729
TI  - Computational protein design: structure, function and combinatorial diversity.
AB  - Computational protein design has blossomed with the development of methods for
      addressing the complexities involved in specifying the structure, sequence and
      function of proteins. Recent applications include the design of novel functional
      membrane and soluble proteins, proteins incorporating non-biological components
      and protein combinatorial libraries.

PMID- 17524730
TI  - A young woman with neurofibromatosis and severe hypertension.

PMID- 17524732
TI  - Indications of capsule endoscopy in Henoch-Schonlein syndrome with
      gastrointestinal symptoms.

PMID- 17524733
TI  - Abnormal valsalva maneuver is not always a sign of congestive heart failure.

PMID- 17524734
TI  - Balancing the risks and benefits of celecoxib.

PMID- 17524735
TI  - Airway obstruction in never smokers.

PMID- 17524736
TI  - Using the pneumonia severity index to guide hospitalization decisions.

PMID- 17524737
TI  - Pneumonia Severity Index (PSI) lacking in breadth of applicability.

PMID- 17524738
TI  - Thyrotoxic hypokalemic periodic paralysis in a white man.

PMID- 17524739
TI  - Baclofen not comparable to diazepam for alcohol withdrawal.

PMID- 17524741
TI  - Baclofen for alcohol withdrawal: not comparable to the gold standard
      (benzodiazepines).

PMID- 17524742
TI  - Who will care for the frail elderly?

PMID- 17524743
TI  - Are patients with a patent foramen ovale at increased risk of stroke? A billion
      dollar question.

PMID- 17524744
TI  - Direct-to-consumer advertising of pharmaceuticals.
AB  - Since the US Food and Drug Administration (FDA) released new guidelines on
      broadcast direct-to-consumer advertising in 1997, the prevalence of direct-to
      consumer advertising of prescription drugs has increased exponentially. The
      impact on providers, patients, and the health care system is varied and dynamic,
      and the rapid changes in the last several years have markedly altered the health
      care landscape. To continue providing optimal medical care, physicians and other
      health care providers must be able to manage this influence on their practice,
      and a more thorough understanding of this phenomenon is an integral step toward
      this goal. This review will summarize the history of direct-to-consumer drug
      advertisements and the current regulations governing them. It will summarize the
      evidence concerning the impact of direct-to-consumer advertising on the public,
      providers, and the health care system, and conclude with observations regarding
      the future of direct-to-consumer advertising.

PMID- 17524745
TI  - Atrial fibrillation in the elderly.
AB  - Atrial fibrillation is increasingly prevalent among older adults. It causes
      approximately 24% of strokes in patients aged 80 to 89 years. The management of
      atrial fibrillation is directed at preventing thromboembolism and controlling the
      heart rate and rhythm. Stroke prevention is most effectively accomplished through
      administering anticoagulants such as warfarin, although older patients have
      higher hemorrhagic risk. Cognitive dysfunction, functional impairments, and
      increased fall risk further complicate warfarin management in elderly patients.
      The use of risk stratification schemes can help guide the anticoagulation
      decision, although the benefits of warfarin generally outweigh the risks in most
      older patients with atrial fibrillation. Pharmacologic rate control has been
      shown to result in similar outcomes compared with pharmacologic restoration of
      sinus rhythm and should be the initial therapy for elderly patients. Anti
      arrhythmic medications should be selected based on an individual patient's
      coexisting medical conditions. In symptomatic patients who fail pharmacologic
      therapy, invasive strategies such as AV nodal ablation may help improve quality
      of life and symptoms, although such strategies do not obviate the need for
      antithrombotic therapy.

PMID- 17524746
TI  - HIV-associated nephropathy in the era of antiretroviral therapy.
AB  - With improved survival in the era of antiretroviral therapy, kidney disease has
      emerged as an important complication of Human Immunodeficiency Virus (HIV)
      infection and antiretroviral therapy. The classic kidney disease of HIV
      infection, HIV-associated nephropathy, occurs almost exclusively in patients of
      African descent. HIV-associated nephropathy is characterized by collapsing focal
      segmental glomerulosclerosis with associated tubular dilatation and interstitial
      inflammation, although the histology may be more subtle in patients receiving
      antiretroviral therapy. Renal epithelial cells are infected by HIV-1, which
      results in epithelial cell proliferation and induction of local inflammatory
      pathways. Even with appropriate therapy, the kidney is a reservoir for HIV-1.
      Although the widespread introduction of antiretroviral therapy has had a
      beneficial impact on the epidemiology of HIV-associated nephropathy, the burden
      of kidney disease is likely to increase as a result of antiretroviral toxicity,
      reduction in competing mortality risks, and the increasing prevalence of HIV-1
      infection in patients at risk for kidney disease.

PMID- 17524747
TI  - Falls in older adults: risk assessment, management and prevention.
AB  - Falls are a common and serious problem for older adults. This article reviews
      practical aspects of the evaluation and management of this disorder in the
      ambulatory setting. Older patients should be screened for falls or changes in
      mobility as part of their annual health maintenance examination. Most falls are
      due to multiple factors, including disorders of gait, balance, strength, and
      vision. Polypharmacy and certain medications contribute to falls in many patients
      and can be a remediable factor. Many falls can be prevented through
      individualized multicomponent interventions. Exercise programs, rehabilitation,
      medication management, and treatment of vitamin D deficiency are the most
      effective single interventions. Referral to a geriatrician should be considered
      for patients with other common geriatric syndromes, such as cognitive impairment,
      incontinence, or depression.

PMID- 17524748
TI  - Allergic respiratory disease in the elderly.
AB  - Allergic asthma and allergic rhinosinusitis are typically considered disorders of
      children and young adults. As a result, these diseases are frequently not
      considered in the differential diagnosis of nasal obstruction, cough, wheeze, and
      dyspnea in older individuals. However, many older adults have long-standing
      allergic disorders or develop them later in life. This article addresses the
      complexities of diagnosis and treatment of allergic respiratory diseases in
      seniors.

PMID- 17524749
TI  - High-speed heart.

PMID- 17524750
TI  - Growth by association.

PMID- 17524751
TI  - A seriously swollen lip.

PMID- 17524752
TI  - Now you see it; now you don't.

PMID- 17524753
TI  - A Wilde diagnosis.

PMID- 17524754
TI  - Body mass, fitness and survival in veteran patients: another obesity paradox?
AB  - PURPOSE: The paradox of obesity in patients with heart failure (HF) also has been
      observed in non-HF veteran patients. Veterans had to have met military fitness
      requirements at the time of their enlistment. Therefore, we assessed the relation
      of body mass index (BMI) to mortality in a clinical cohort of non-HF veterans,
      adjusting for fitness. METHODS: After excluding HF patients (n=580), the study
      population comprised 6876 consecutive patients (mean age 58 [+/-11] years)
      referred for exercise testing. Patients were classified by BMI category: normal
      weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), or obese (BMI >
      or =30.0 kg/m2). The association between BMI, fitness, other clinical variables,
      and all-cause mortality was assessed by Cox proportional hazards analysis.
      RESULTS: During a mean (+/-SD) follow-up of 7.5+/-4.5 years, a total of 1571
      (23%) patients died. In a multivariate analysis including clinical, risk factor,
      and exercise test data, higher BMI was associated with better survival.
      Expressing the data by BMI category, obese patients were 22% less likely to die
      (relative risk [RR]=0.78, 95% confidence interval [CI], 0.69-0.90, P<.001) than
      patients of normal weight. After further adjustment for cardiorespiratory fitness
      (CRF), this relationship strengthened such that mortality risk for the obese
      category was 35% lower (RR=0.65, 95% CI, 0.57-0.76, P<.001), versus the normal
      weight category. CONCLUSIONS: As has been observed in HF patients, obesity was
      associated with a substantially lower mortality risk in a clinical population of
      non-HF veterans. Higher CRF and obesity in later life may account for an obesity
      paradox in this population.

PMID- 17524755
TI  - Selective serotonin reuptake inhibitor use by patients with acute coronary
      syndromes.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors are commonly used to treat
      anxiety, depression, and other conditions that commonly affect patients with
      coronary artery disease. Selective serotonin reuptake inhibitors inhibit platelet
      activation and may, therefore, affect outcomes in patients with acute coronary
      syndromes. METHODS: A retrospective study was performed of 1254 patients with
      acute coronary syndromes comparing in-hospital bleeding and cardiac event rates
      in 158 patients who received a selective serotonin reuptake inhibitor and a
      propensity score-matched group of patients who did not. All patients were treated
      with a glycoprotein IIb/IIIa inhibitor and almost all also received aspirin,
      clopidogrel, and heparin. RESULTS: Patients who received a selective serotonin
      reuptake inhibitor were significantly more likely to experience any bleeding
      (37.3% vs 26.6%, OR 1.65, 95% confidence interval (CI), 1.02-2.66, P =.04) and
      significantly less likely to experience recurrent myocardial ischemia, heart
      failure, or asymptomatic cardiac enzyme elevation while in the hospital (7.0% vs
      13.9%, OR 0.46, 95% CI, 0.22-0.99, P =.04). No differences were observed in
      death, myocardial infarction during the hospitalization, urgent
      revascularization, or major bleeding. Bleeding and cardiac events were not
      affected by antidepressants other than selective serotonin reuptake inhibitors.
      CONCLUSIONS: Selective serotonin reuptake inhibitor use during a hospitalization
      for an acute coronary syndrome is associated with reduced rates of recurrent
      ischemia, heart failure, or cardiac enzyme elevation at the expense of increased
      bleeding in patients receiving maximal conventional antiplatelet medications and
      heparin. Clinicians should be aware of this association when treating patients
      with an acute coronary syndrome.

PMID- 17524756
TI  - Improving risk assessment with cardiac testing in peripheral arterial disease.
AB  - PURPOSE: The study's objective was to evaluate the prognostic value of left
      ventricular ejection fraction and stress-induced ischemia during dobutamine
      stress echocardiography, in addition to ankle-brachial index measurements and
      clinical risk factors in patients with suspected or known peripheral arterial
      disease. METHODS: In 852 patients with suspected or known peripheral arterial
      disease (mean age 63 years, 70% male), the ankle-brachial index was measured,
      left ventricular ejection fraction was assessed, and all patients underwent
      additional stress testing. Endpoints were all-cause mortality and hard cardiac
      events (cardiac death or nonfatal myocardial infarction). RESULTS: During a mean
      follow-up of 7.6+/-4.4 years, death occurred in 288 patients (34%), and hard
      cardiac events occurred in 216 patients (25%). Mean left ventricular ejection
      fraction was 50%+/-17%, and stress-induced ischemia was observed in 352 patients
      (41%). In multivariate analysis with adjustment for clinical risk factors and
      ankle-brachial index, each 5% decrease in left ventricular ejection fraction was
      associated with increased all-cause mortality (hazard ratio [HR] 1.05, 95%
      confidence interval [CI], 1.02-1.09) and hard events (HR 1.14, 95% CI, 1.08
      1.21). Stress-induced ischemia also independently predicted all-cause mortality
      (HR 2.01, 95% CI, 1.38-2.79) and hard events (HR 2.06, 95% CI, 1.39-3.08). Left
      ventricular ejection fraction and stress-induced ischemia provided incremental
      prognostic information over clinical data and ankle-brachial index values (P
      <.001). CONCLUSIONS: Left ventricular ejection fraction and stress-induced
      ischemia independently predict long-term outcome and improve prognostic risk
      assessment, in addition to ankle-brachial index and clinical risk factors in
      patients with suspected or known peripheral arterial disease.

PMID- 17524757
TI  - The safety of warfarin therapy in the nursing home setting.
AB  - PURPOSE: We examined the preventability of adverse warfarin-related events and
      potential adverse warfarin-related events ("near misses") in the nursing home
      setting. METHODS: We performed a cohort study of all long-term care residents of
      25 nursing homes (bed size range, 90-360) in Connecticut during a 12-month
      observation period. The total number of residents in these facilities ranged from
      2946 to 3212 per quarter. There were 490 residents who received warfarin therapy.
      Possible warfarin-related incidents were detected by quarterly retrospective
      review of nursing home records by trained nurse abstractors. Each incident was
      independently classified by 2 physician-reviewers to determine whether it
      constituted a warfarin-related event, its severity, and its preventability. The
      primary outcome was an adverse warfarin-related event, defined as an injury
      associated with the use of warfarin. Potential adverse warfarin-related events
      were defined as situations in which the international normalized ratio (INR) was
      noted to be 4.5 or greater, an error in management was noted, but no injury
      occurred. We also assessed time in specified INR ranges per nursing home resident
      day on warfarin. RESULTS: Over the 12-month observation period, 720 adverse
      warfarin-related events and 253 potential adverse warfarin-related events were
      identified. Of the adverse warfarin-related events, 625 (87%) were characterized
      as minor, 82 (11%) were deemed serious, and 13 (2%) were life-threatening or
      fatal. Overall, 29% of the adverse warfarin-related events were judged to be
      preventable. Serious, life-threatening, or fatal events occurred at a rate of
      2.49 per 100 resident-months; 57% of these more severe events were considered
      preventable. Errors resulting in preventable events occurred most often at the
      prescribing and monitoring stages of warfarin management. The percentages of time
      in the less than 2, 2 to 3, and more than 3 INR ranges were 36.5%, 49.6%, and
      13.9%, respectively. CONCLUSIONS: The use of warfarin in the nursing home setting
      presents substantial safety concerns for patients. Adverse events associated with
      warfarin therapy are common and often preventable in the nursing home setting.
      Prevention strategies should target the prescribing and monitoring stages of
      warfarin management.

PMID- 17524758
TI  - Maltreatment of Strongyloides infection: case series and worldwide physicians-in
      training survey.
AB  - BACKGROUND: Strongyloidiasis infects hundreds of millions of people worldwide and
      is an important cause of mortality from intestinal helminth infection in
      developed countries. The persistence of infection, increasing international
      travel, lack of familiarity by health care providers, and potential for
      iatrogenic hyperinfection all make strongyloidiasis an important emerging
      infection. METHODS: Two studies were performed. A retrospective chart review of
      Strongyloides stercoralis cases identified through microbiology laboratory
      records from 1993-2002 was conducted. Subsequently, 363 resident physicians in 15
      training programs worldwide were queried with a case scenario of
      strongyloidiasis, presenting an immigrant with wheezing and eosinophilia. The
      evaluation focused on resident recognition and diagnostic recommendations.
      RESULTS: In 151 strongyloidiasis cases, stool ova and parasite sensitivity is
      poor (51%), and eosinophilia (>5% or >400 cells/microL) commonly present (84%).
      Diagnosis averaged 56 months (intra-quartile range: 4-72 months) after
      immigration. Presenting complaints were nonspecific, although 10% presented with
      wheezing. Hyperinfection occurred in 5 patients prescribed corticosteroids, with
      2 deaths. Treatment errors occurred more often among providers unfamiliar with
      immigrant health (relative risk of error: 8.4; 95% confidence interval, 3.4-21.0;
      P <.001). When presented with a hypothetical case scenario, US physicians-in
      training had poor recognition (9%) of the need for parasite screening and
      frequently advocated empiric corticosteroids (23%). International trainees had
      superior recognition at 56% (P <.001). Among US trainees, 41% were unable to
      choose any parasite causing pulmonary symptoms. CONCLUSIONS: Strongyloidiasis is
      present in US patients. Diagnostic consideration should occur with appropriate
      exposure, nonspecific symptoms including wheezing, or eosinophilia (>5% relative
      or >400 eosinophils/microL). US residents' helminth knowledge is limited and
      places immigrants in iatrogenic danger. Information about Strongyloides should be
      included in US training and continuing medical education programs.

PMID- 17524759
TI  - Kidney disease, Framingham risk scores, and cardiac and mortality outcomes.
AB  - BACKGROUND: The Framingham equations were developed to predict incident coronary
      heart disease. It remains unknown how the presence of chronic kidney disease
      affects their performance. METHODS: Individuals without preexisting
      cardiovascular disease aged 45 to 74 years from the Atherosclerosis Risk in
      Communities and Cardiovascular Health Studies were analyzed. Using sex- and race
      specific Cox models, we evaluated the 5-year risk of coronary heart disease and
      mortality events associated with both chronic kidney disease and Framingham risk
      score, the absolute risk of events caused by kidney disease, and model
      discrimination. RESULTS: Among 15,717 subjects, 756 (4.8%) had kidney disease.
      The Framingham risk score independently predicted cardiac and mortality events in
      all subgroups, whereas kidney disease predicted events in all subgroups except
      cardiac events in white women. After adjustment for traditional risk factors, the
      increase in cardiac and mortality events per 1000 person-years attributable to
      kidney disease was 4.3 and 13.7 for white men, 16.1 and 40.5 for African American
      men, 1.2 and 5.8 for white women, and 13.6 and 14.2 for African American women,
      respectively. This represented an additional 17,000 and 12,000 cardiac events and
      63,000 and 19,000 deaths per year among whites and African Americans,
      respectively. Mortality rates attributable to kidney disease, diabetes, and
      smoking were comparable. Accounting for kidney disease improved discrimination
      for only mortality outcomes in white men and African American women. CONCLUSIONS:
      Chronic kidney disease in a community-based population is an important predictor
      of cardiac and mortality events, particularly in African Americans, but it does
      not improve discrimination of Framingham equations.

PMID- 17524760
TI  - High FVIII level is associated with idiopathic portal vein thrombosis in South
      India.
AB  - BACKGROUND: In the majority of the cases of portal vein thrombosis in India, the
      etiology cannot be determined. A high level of factor VIII (FVIII) is a risk
      factor for venous thromboembolism. METHODS: In this study from South India, FVIII
      was estimated in 32 patients with idiopathic portal vein thrombosis (PVT), 12
      healthy controls and 12 disease controls with chronic liver disease. RESULTS:
      Eighty-four percent of the patients with portal vein thrombosis (27/32) vs 17% of
      healthy controls (2/12) had high factor VIII levels (P <.0001). FVIII levels were
      significantly different between the subset of PVT patients with normal liver
      function compared with healthy controls (P <.001) and also between the subset of
      PVT patients with abnormal liver function compared with disease controls (P
      <.05). CONCLUSIONS: A high factor VIII level seems to contribute to the
      development of portal vein thrombosis in India.

PMID- 17524761
TI  - Late to the feast: primary care and US health policy.

PMID- 17524762
TI  - Ancient Japanese medicine in the Tale of Genji.

PMID- 17524763
TI  - Quantum chemical computations and Fourier transform infrared spectral studies of
      a nonlinear food dye E110.
AB  - Fourier transform infrared (FTIR) spectrum of a well-known food dye sunset yellow
      FCF (E110) has been recorded and analysed. Assignments of the vibrational
      spectrum has been facilitated by density functional theory (DFT) calculations.
      The results of the optimized molecular structure obtained on the basis of B3LYP
      with 6-31G(d) along with the 'LANL2DZ' basis sets give clear evidence for the
      intramolecular charge transfer (ICT) and strong hydrogen bonding enhancing the
      optical nonlinearity of the molecule. The first hyperpolarizability of the acidic
      monoazo dye 'E110' is computed. Azo stretching frequencies have been lowered due
      to conjugation and pi-electron delocalization. Hydroxyl vibrations with
      intramolecular H-bonding are analyzed, supported by the computed results. The
      natural bond orbitals (NBO) analysis confirms this strong hydrogen bond between
      the hydrogen of the hydroxyl group and nitrogen of the azo group of the molecule.
      Assignments of benzene and naphthalene ring vibrations are found to agree well
      with the theoretical wave numbers.

PMID- 17524764
TI  - Distance-adjusted motor threshold for transcranial magnetic stimulation.
AB  - OBJECTIVE: To examine the relationship between coil-cortex distance and effective
      cortical stimulation using transcranial magnetic stimulation (TMS) in the left
      and right motor cortex. We also compare the effect of coil-cortex distance using
      50 and 70 mm figure-eight stimulating coils. METHODS: Coil-cortex distance was
      manipulated within each participant using 5 and 10 mm acrylic separators placed
      between the coil and scalp surface. The effect of cortical stimulation was
      indexed by resting motor threshold (MT). RESULTS: Increasing distance between the
      coil and underlying cortex was associated with a steep linear increase in MT. For
      each additional millimetre separating the stimulating coil from the scalp
      surface, an additional approximately 2.8% of absolute stimulator output
      (approximately 0.062 T) was required to reach MT. The gradient of the observed
      distance effect did not differ between hemispheres, and no differences were
      observed between the 50 and 70 mm TMS coils. CONCLUSIONS: Coil-cortex distance
      directly influences the magnitude of cortical stimulation in TMS. The
      relationship between TMS efficacy and coil-cortex distance is well characterised
      by a linear function, providing a simple and effective method for scaling
      stimulator output to a distance adjusted MT. SIGNIFICANCE: MT measured at the
      scalp-surface is dependent on the underlying scalp-cortex distance, and therefore
      does not provide an accurate index of cortical excitability. Distance-adjusted MT
      provides a more accurate index of cortical excitability, and improves the safety
      and efficacy of MT-calibrated TMS.

PMID- 17524765
TI  - Sensitivity of conventional motor nerve conduction examination in detecting
      patchy demyelination: a simulated model.
AB  - OBJECTIVE: To evaluate, in 5 simulated motor nerves with patchy demyelination:
      (1) the sensitivity of the conventional motor conduction examination; (2) the
      conduction velocity of single axons (SA-CV). METHODS: Four damaged segments were
      simulated in each nerve. Myelin impairment was generated by varying two
      parameters: (1) percent reduction in conduction velocity, i.e. degree of damage
      (DEGREE); (2) percentage of affected axons, i.e. extent of damage (EXTENT).
      Myelin impairment was simulated in axons with different diameters. We evaluated:
      (1) conduction velocity; (2) temporal dispersion of the negative phase of
      compound motor action potential (CMAP); (3) amplitude decay of CMAP; (4) SA-CV of
      20 randomly-chosen axons. RESULTS: When the damage involved both large and small
      axons, the conduction velocity was pathological only when severe myelin damage
      involved a large number of axons. Temporal dispersion and amplitude decay were
      more sensitive than conduction velocity in detecting the damage. In damage
      involving only large axons or only small axons, all parameters remained in the
      normal range. SA-CV evaluation was much more sensitive than the conventional
      studies, regardless of the diameter of the damaged axons. CONCLUSIONS:
      Conventional studies are not sensitive in detecting minimal myelin damage.
      Decomposing the CMAPs and randomly studying 20 SA-CVs would increase the
      sensitivity of damage detection. SIGNIFICANCE: These results contribute to a
      better understanding of the relationship between axonal properties and
      neurophysiological findings in motor nerve demyelination.

PMID- 17524766
TI  - Biometry and formula accuracy with intraocular lenses used for cataract surgery
      in extreme hyperopia.
AB  - PURPOSE: To audit intraocular lens (IOL) power predictions for cataract surgery
      in extreme hyperopia and to compare the accuracy across different biometry
      formulae and IOL types. DESIGN: A retrospective analysis of 76 eyes from 56
      patients undergoing cataract surgery with IOLs ranging in power from 30 to 35
      diopters (D). METHODS: Axial lengths, corneal powers and anterior chamber depths
      were measured with ultrasound or optical methods, and the IOLMaster (Carl Zeiss
      Meditech, Inc, Dublin, California, USA) software was used to predict the
      refractive outcome for each IOL used. Differences between the predicted and
      actual postoperative refraction were then analyzed for each formula. RESULTS: In
      practice, 55% of patients were within +/-1.0 D of the refraction predicted by
      their surgeon. In theory, the Haigis formula would have given the smallest mean
      refractive error (+0.51 +/- 0.12 D), followed by the Hoffer Q (-0.70 +/- 0.14 D),
      Holladay 1 (-1.11 +/- 0.13 D), and SRK/T formulae (-1.45 +/- 0.14 D). The Haigis
      formula overpredicted the lens power required, which would have generated a
      myopic result. The other formulae underpredicted the lens power required and
      would have generated a hyperopic result. There was a significant difference
      between lens designs: the Haigis was more accurate for open-loop, whereas the
      Hoffer Q was more accurate for plate-haptic lenses. The anterior chamber depth
      measurement could also be used to predict changes in intraocular pressure after
      surgery. CONCLUSION: This represents the largest published series to date of
      biometry predictions for cataract surgery in extreme hyperopia and confirms the
      Haigis formula to be the most accurate. A consistent difference between open-loop
      and plate-haptic lenses suggests that haptic design may influence the effective
      lens position in very small eyes. We further propose a simple formula to optimize
      the Haigis and Hoffer Q formulae in patients with extreme hyperopia.

PMID- 17524767
TI  - Retinal vascular caliber, diabetes, and retinopathy.
AB  - PURPOSE: To assess the relationship of retinal vessel caliber with diabetes and
      diabetic retinopathy (DR). DESIGN: Population-based cross-sectional analysis of
      the Blue Mountains Eye Study, Australia (n = 3,654, age >or=49 years). METHODS:
      Diabetes was defined as physician-diagnosed or fasting blood glucose >or= 7.0
      mmol/l; impaired fasting glucose as fasting glucose 6.1 to 6.9 mmol/l. DR was
      graded from retinal photographs. Retinal vessel caliber was measured from
      digitized images. RESULTS: After controlling for age, gender, blood pressure, and
      other factors, mean retinal venular caliber was significantly wider in
      participants with moderate-severe nonproliferative DR (severe 262.7 microm;
      moderate 236.7 microm) than in nondiabetic participants (221.9 microm) or
      participants with diabetes but no DR (221.2 microm) (P < .0001). Mean retinal
      arteriolar caliber was significantly wider in participants with diabetes (193.5
      microm) than in nondiabetic participants (190.2 microm) (P < .01). CONCLUSIONS:
      Increasing severity of DR in persons with diabetes is associated with widening of
      retinal venular caliber.

PMID- 17524768
TI  - Alcohol consumption and the 15-year cumulative incidence of age-related macular
      degeneration.
AB  - PURPOSE: To investigate alcohol consumption as a risk factor for the 15-year
      cumulative incidence and progression of age-related macular degeneration (AMD).
      DESIGN: Prospective population-based study in Beaver Dam, WI with four
      examinations at five-year intervals initiated in 1988 (n = 3,509 contributed data
      for this analysis). METHODS: History of alcohol consumption was obtained via
      questionnaire. Cumulative incidence of early AMD, exudative AMD, pure geographic
      atrophy, and progression of AMD were assessed from fundus photographs taken at
      each examination. RESULTS: Heavy drinking (four or more drinks daily) at baseline
      was related to the 15-year cumulative incidence of pure geographic atrophy in men
      (odds ratio, 9.2; 95% confidence interval, 1.7 to 51.2). There were no consistent
      associations with the amount of beer, wine, or liquor consumption and the
      incidence or progression of AMD. CONCLUSIONS: Alcohol consumption is unlikely to
      strongly increase (or decrease) the risk of AMD.

PMID- 17524769
TI  - Quantitative analysis of retinal vessel diameter reduction after photocoagulation
      treatment for retinopathy of prematurity.
AB  - PURPOSE: To evaluate the feasibility of using semiautomated analysis of digital
      fundus images to quantify effects of photocoagulation on retinal vessel diameter
      in retinopathy of prematurity (ROP). DESIGN: Case series. METHODS: Fourteen eyes
      of seven patients with threshold ROP and 12 eyes of six controls were included.
      Fundus images were captured before and after photocoagulation, or one to three
      weeks apart in controls, using an NM200D camera (Nidek, Inc, Aichi, Japan).
      VesselMap software (Imedos, Jena, Germany) measured vessel diameter. The t test
      analysis was used to assess vessel changes. RESULTS: The authors observed a
      significant reduction in average largest retinal vein diameter of -18% +/- 16%
      (+/-1 standard deviation). The average largest artery diameter trended down by 
      12% +/- 16%. Compared with controls, diameter reduction was significant in veins
      (P = .014) and arteries (P = .016). CONCLUSIONS: The diameter of retinal vessels
      decreases after photocoagulation. VesselMap analysis of digital images is
      feasible and may be helpful in quantifying treatment effects.

PMID- 17524770
TI  - The prognostic influence of chronicity of rhegmatogenous retinal detachment on
      anatomic success after reattachment surgery.
AB  - PURPOSE: To investigate anatomic success after surgery for chronic retinal
      detachment. DESIGN: Retrospective, case series review. METHODS: The surgical
      outcomes of reattachment surgery for 36 eyes of 35 patients with chronic retinal
      detachments are reported and are compared with the outcomes for 129 fresh retinal
      detachments. RESULTS: After exclusion of retinal detachments secondary to retinal
      dialysis and of cases with proliferative vitreoretinopathy (PVR), success after a
      single procedure was seen in eight of 14 (57.1%) chronic retinal detachments, and
      this compares with 92 of 107 (86.0%) fresh retinal detachments (P = .0161).
      CONCLUSIONS: Chronicity of retinal detachment at presentation is an important and
      poor prognostic indicator for reattachment surgery.

PMID- 17524771
TI  - Intraocular pressure effects of pegaptanib (Macugen) injections in patients with
      and without glaucoma.
AB  - PURPOSE: To determine if pegaptanib (Macugen) [Eyetech Pharmaceuticals; Pfizer
      Inc, New York, New York, USA] injections cause adverse intraocular pressure (IOP)
      effects in patients with and without glaucoma. DESIGN: Retrospective chart
      review. METHODS: Review of 75 eyes treated with intravitreal injections of
      pegaptanib (0.09 ml). The effect of these injections on IOP was analyzed. Most
      patients received prophylactic IOP-lowering medications. RESULTS: The mean
      preinjection IOP based on the first injection of each patient was 14 +/- 3 mm Hg;
      at one minute postinjection, 38 +/- 14 mm Hg, at three to 10 minutes was 34 +/- 9
      mm Hg, and at 11 to 20 minutes was 26 +/-10 mm Hg, respectively. Most patients'
      IOPs had significantly diminished by 30 minutes postinjection. CONCLUSION:
      Pegaptanib injections result in a significant transient rise in IOP that
      considerably diminishes by 30 minutes postinjection but can take up to one hour.
      This may be damaging to the optic nerve, particularly in patients with advanced
      glaucoma.

PMID- 17524772
TI  - Tunneled scleral incision to prevent vitreal reflux after intravitreal injection.
AB  - PURPOSE: To investigate the efficacy of tunneled scleral incision compared with
      standard straight scleral incision to prevent vitreal reflux after intravitreal
      (IVT) injection. DESIGN: Prospective comparative controlled nonrandomized
      clinical study. METHODS: Eighty-eight eyes undergoing IVT-injection were
      allocated into four groups to compare the vitreal reflux after injection of 0.1
      ml of triamcinolone acetonide (TA) and Avastin using a tunneled vs straight
      injection technique. The amount of intraoperative drug reflux was estimated by
      measuring the width of the subconjunctival bleb. RESULTS: The mean measured
      reflux of volume was statistically less with the tunneled scleral incision (1.13
      mm standard deviation [SD] +/- 1.16 for TA; 1.13 mm SD +/- 1.39 for Avastin) than
      in eyes undergoing the straight scleral injection (3.00 mm SD +/- 1.77 for TA;
      3.18 mm SD +/- 1.68 for Avastin) for both Avastin and TA IVT-injections groups (P
      < .001). CONCLUSIONS: The tunneled scleral incision promotes statistically
      significant less vitreal reflux for IVT drug injection.

PMID- 17524773
TI  - Measurement of greatest linear diameter for choroidal neovascular membrane using
      optical coherence tomography.
AB  - PURPOSE: Correlation of greatest linear diameter (GLD) of choroidal
      neovascularization (CNV) measured by fundus fluorescein angiography (FA) with
      optical coherence tomography (OCT). DESIGN: Retrospective noninterventional
      observational case series. METHODS: Patients who underwent verteporfin therapy
      for subfoveal classic CNV were assessed. GLD of CNV was calculated manually from
      mean of 6 line scans. GLD measured on OCT and FA was correlated by assessing the
      agreement of the two techniques by interclass correlation and Bland and Altman
      technique. RESULTS: Twenty-seven eyes of 27 patients with subfoveal classic CNV
      were included. The mean age was 49.3 +/- 18.6 years. The mean GLD calculated on
      FA was 1973.3 microm and OCT was 2024.2 microm. Substantial agreement was
      observed between GLD measured on FA and OCT (Inter-Class Correlation [ICC] =
      0.77%; 95% confidence interval, 0.56 to 0.89). CONCLUSIONS: GLD measured on OCT
      correlates to FA measurement. This method could be beneficial where FA is
      contraindicated while contemplating photodynamic therapy (PDT).

PMID- 17524774
TI  - Influence of intraocular pressure on retinal vascular caliber measurements in
      children.
AB  - PURPOSE: To determine whether intraocular pressure (IOP) influences retinal
      vascular caliber in young children, in order to provide a better understanding of
      its physiological determinants. DESIGN: Cross-sectional study. METHODS: Three
      hundred and eighty-six Chinese children seven to nine years of age participated
      in the Singapore Cohort Study of the Risk factors for Myopia (SCORM). IOP was
      measured by noncontact tonometry. Retinal vascular calibers were measured from
      retinal photographs using a computer-based program following standardized
      protocols. RESULTS: After adjusting for age, gender, body mass index, corneal
      thickness, spherical equivalent refraction, axial length, and birth weight, mean
      retinal arteriolar and venular caliber were similar across the distribution of
      IOP (arteriolar caliber of 155.2 microm, 155.6 microm, 153.8 microm, 154.2
      microm, P value for trends, 0.45; and venular caliber of 225.7 microm, 220.6
      microm, 224.5 microm, 222.7 microm, P value for trends, 0.53; comparing
      increasing quartiles of IOP). CONCLUSIONS: Our study provides no evidence that
      IOP influences retinal vascular caliber in healthy young children.

PMID- 17524775
TI  - Clinical characteristics and outcome of Candida keratitis.
AB  - PURPOSE: To characterize the clinical features and therapeutic outcome of Candida
      keratitis. DESIGN: Retrospective, observational case series. METHODS: We reviewed
      26 patients treated for Candida keratitis, including two with recurrent keratitis
      and one with bilateral infection. RESULTS: Of 29 keratitis episodes resulting
      from Candida albicans (n = 20) or Candida parapsilosis (n = 9), 16 (55%)
      complicated chronic ocular surface disease, and nine (31%) followed previous
      keratoplasty. Only two were clinically suspected to have keratomycosis at initial
      presentation, and 21 (72%) used antibacterial therapy before corneal scrapings.
      Reconstructive keratoplasty occurred more often in previously grafted eyes (P =
      .03). Visual outcome was 20/60 or better in six (100%) medically treated eyes
      with good presenting visual acuity but in only five eyes (24%) with worse initial
      vision (P = .002). CONCLUSIONS: Candida keratitis is an opportunistic infection
      of a compromised cornea that often is misdiagnosed initially and, despite
      antifungal therapy, occasionally requires corneal grafting.

PMID- 17524776
TI  - Bacterial keratitis after primary pediatric penetrating keratoplasty.
AB  - PURPOSE: To determine the prevalence, microbiological profile, and prognosis for
      bacterial keratitis after primary pediatric penetrating keratoplasty (PKP).
      DESIGN: Retrospective case series. METHODS: Retrospective review of all cases of
      primary PKP performed in children 12 years of age or younger at the King Khaled
      Eye Specialist Hospital between January 1, 1990 and December 31, 2005 and
      inclusion of all postoperative cases of culture-positive, bacterial keratitis.
      RESULTS: Culture-positive bacterial keratitis developed in 35 (17.3%) of 202
      primary keratoplasties. Gram-positive organisms were cultured in 91.4% of
      infected eyes and accounted for 77.6% of isolates. Streptococcus pneumoniae was
      the most common organism. No eyes achieved a final visual acuity of 20/40 or
      better, while 65.7% had hand motions or worse. CONCLUSIONS: Bacterial keratitis
      after pediatric keratoplasty is a serious complication that is associated with a
      high risk of graft failure and poor visual outcome.

PMID- 17524777
TI  - Comparison of central corneal thickness measurements by visante anterior segment
      optical coherence tomography with ultrasound pachymetry.
AB  - PURPOSE: To compare the measurement of the central corneal thickness (CCT) by
      Visante (Carl Zeiss Meditec, Dublin, California, USA) anterior segment optical
      coherence tomography (AS-OCT) with ultrasound pachymetry. DESIGN: Population
      based, cross-sectional study. METHODS: Participants were part of a population
      based study of 3280 Malay subjects aged 40 to 80 years in Singapore. Ultrasound
      pachmetry of CCT was performed on all participants and approximately 10%
      underwent further evaluation with AS-OCT. RESULTS: Two hundred and eighty-five
      consecutive subjects were included, with a mean age of 57.9 (+/- 10.8) years. CCT
      as measured by ultrasound pachymetry was highly correlated with the equivalent AS
      OCT reading (The Pearson correlation coefficient = 0.93, P < .001). However,
      Bland-Altman analysis showed that CCT as measured by ultrasound pachymetry was
      significantly higher by 16.5 +/- 11.7 microm (limits of agreement -6.1 to 39.1, P
      < .001). CONCLUSIONS: CCT measured by Visante AS-OCT was highly correlated with
      that from ultrasound pachymetry. However, CCT readings by Visante AS-OCT were
      consistently less than that of ultrasound pachymetry.

PMID- 17524778
TI  - Conjunctival posttransplantation lymphoproliferative disorder.
AB  - PURPOSE: To describe a patient with conjunctival posttransplantation
      lymphoproliferative disorder (PTLD). DESIGN: Interventional case report. METHODS:
      A 8-year-old boy, three months status post bone marrow transplantation with
      bilateral enlarged gelatinous bulbar conjunctiva was examined. Biopsy of the
      bulbar conjunctiva was performed. RESULTS: Conjunctival biopsy revealed a
      polymorphous infiltrate of lymphoid cells with large atypical immunoblastic
      lymphoma cells, plasmacytoid lymphocytes, and plasma cells. B-cell markers CD20
      and CD79a were positive. Plasma cells exhibited restriction for kappa
      immunoglobulin light chain and were positive for CD79a. Most cells were positive
      for Epstein-Barr virus (EBV) encoded ribonucleic acid. EBV-related polymorphic
      PTLD was diagnosed and treated with discontinuation of cyclosporine, reduction in
      prednisone dosage and administration of EBV-specific cytotoxic T lymphocytes. The
      conjunctival lesions resolved during the next five weeks. CONCLUSIONS:
      Posttransplantation lymphoproliferative disorder rarely involves the ocular
      structures with most cases presenting as a masquerade syndrome. This case
      illustrates that PTLD can involve the conjunctiva and further expands the
      clinical spectrum of ocular PTLD.

PMID- 17524779
TI  - Long-term outcomes of amniotic membrane transplantation for repair of leaking
      glaucoma filtering blebs.
AB  - PURPOSE: To report long-term results of human preserved amniotic membrane
      transplant (AMT) vs conjunctival advancement for repair of late-onset glaucoma
      filtering bleb leakage. DESIGN: Randomized, controlled trial (n = 30). METHODS:
      Rates of bleb failure (reoperation for glaucoma or recurrent bleb leak) were
      compared. RESULTS: Median follow-up was 80 months. Final intraocular pressure
      (IOP) was 10.9 +/- 0.9 mm Hg with AMT and 12.7 +/- 1.3 mm Hg with conjunctival
      advancement (P = .28). The number of glaucoma medications and final visual
      acuities were similar between groups. Bleb vascularity was significantly less
      with AMT (P = .02). Seven failures occurred with AMT, four requiring reoperation
      for bleb leakage and three requiring reoperation for glaucoma. Four failures
      occurred with conjunctival advancement, one requiring reoperation for leakage and
      three requiring reoperation for glaucoma. Kaplan-Meier survival curves were
      statistically similar between groups, with a trend favoring conjunctival
      advancement (P = .44). CONCLUSIONS: Although prone to early releakage, AMT may be
      a suitable alternative to conjunctival advancement in the long-term.

PMID- 17524780
TI  - Visualization of aqueous shunt position and patency using anterior segment
      optical coherence tomography.
AB  - PURPOSE: To describe the use of anterior segment optical coherence tomography (AS
      OCT) to clarify the position and patency of aqueous shunt devices in the anterior
      chamber of eyes where corneal edema or tube position does not permit a
      satisfactory view. DESIGN: Noncomparative observational case series. METHODS:
      Four cases are reported in which aqueous shunt malposition or obstruction was
      suspected but the shunt could not be seen on clinical examination. The patients
      underwent AS-OCT to identify the position and patency of the shunt tip. RESULTS:
      In each case, AS-OCT provided data regarding tube position and/or patency that
      could not be obtained by slit-lamp examination or by gonioscopy that influenced
      management. CONCLUSIONS: AS-OCT can be used to visualize anterior chamber tubes
      in the presence of corneal edema that precludes an adequate view or in cases
      where the tube is retracted into the cornea. In such cases, AS-OCT is useful in
      identifying shunt patency and position, which helps guide clinical decision
      making.

PMID- 17524781
TI  - Localized retinal nerve fiber layer defects and visual field abnormalities by
      humphrey matrix frequency doubling technology perimetry.
AB  - PURPOSE: To investigate the ability of frequency doubling technology (FDT)
      perimetry to identify eyes with a localized retinal nerve fiber layer (RNFL)
      defect and normal Humphrey C30-2 SITA-Standard visual field (HVF). DESIGN:
      Retrospective case-control study. METHODS: Fifty-four eyes were divided into two
      groups, an abnormal (n = 29) and a normal (n = 25) FDT perimetry group.
      Approximation of the RNFL defect to the macula (angle alpha) and width of the
      defect (angle beta) were measured by RNFL photograph and compared between two
      groups. RESULTS: Angle alpha and angle beta were significantly different between
      two groups (P < .001 by Mann-Whitney U test, respectively). A multivariate
      logistic regression analysis demonstrated that only angle beta was significantly
      associated with FDT perimetry abnormalities (P = .002). CONCLUSIONS: Only 53.7%
      of the eyes with a localized RNFL defect and normal HVF had visual field
      abnormalities identified by FDT perimetry. Width of the RNFL defect was more
      strongly associated with FDT perimetry abnormalities than location of the defect.

PMID- 17524782
TI  - Apolipoprotein E polymorphisms in patients with primary open-angle glaucoma.
AB  - PURPOSE: To investigate apolipoprotein E (APOE) polymorphisms, which are known to
      influence the risk of Alzheimer disease (AD), in patients with primary open-angle
      glaucoma (POAG). DESIGN: Retrospective case-control association study. METHODS:
      Patients with POAG (n = 242) and controls (n = 187) were analyzed for the APOE
      epsilon 2/epsilon 3/epsilon 4 polymorphisms using minisequencing technique.
      RESULTS: The Alzheimer-associated APOE epsilon 4 allele had similar frequencies
      in the POAG group and in the control group. There was no difference between cases
      and controls with regard to APOE genotypes. CONCLUSIONS: If a common pathogenic
      mechanism exists for the two age-related neurodegenerative diseases, POAG and AD,
      it does not involve APOE polymorphisms.

PMID- 17524783
TI  - Treatment of strabismic amblyopia with refractive correction.
AB  - PURPOSE: To report data on the response of previously untreated strabismic
      amblyopia to spectacle correction. DESIGN: Prospective, interventional case
      series. METHODS: Twelve patients with previously untreated strabismic amblyopia
      were prescribed spectacles and examined at five-week intervals until visual
      acuity was not improved from the prior visit. RESULTS: Amblyopic eye acuity
      improved by 2 lines or more from spectacle-corrected baseline acuity in nine of
      the 12 patients (75%), resolving in three (interocular difference <or=1 line).
      Mean change from baseline to maximum improvement was 2.2 +/- 1.8 lines.
      Improvement continued for up to 25 weeks. CONCLUSIONS: These results support the
      suggestion from a prior study that strabismic amblyopia can improve and even
      resolve with spectacle correction alone. Larger studies with concurrent controls
      are needed to confirm or refute these findings.

PMID- 17524784
TI  - Clinical contrast sensitivity testing in patients with infantile nystagmus
      syndrome compared with age-matched controls.
AB  - PURPOSE: To compare contrast sensitivity using a commercially available technique
      between patients with infantile nystagmus syndrome (INS) and controls. DESIGN:
      Prospective, comparative case series. METHODS: The functional acuity contrast
      test (FACT) was used binocularly in patients with INS and aged-matched controls
      with best acuity under normal lighting using a progression of high-quality sine
      wave grating size changes with increasing spatial frequencies. RESULTS: Nine INS
      patients aged 5 to 11 years and 25 controls were tested. The INS patients' best
      binocular acuity ranged from 20/125 to 20/30, and that of the controls was 20/25
      or better. When compared with age-matched controls, INS patients displayed
      deficiencies in contrast sensitivity syndrome using the FACT test. CONCLUSIONS:
      The FACT or a similar testing system may have potential as a commercially
      available outcome measure in clinical trials in patients with INS.

PMID- 17524785
TI  - Proliferating trichilemmal cyst of the eyelid.
AB  - PURPOSE: To report a case of proliferating trichilemmal cyst in a 55-year-old
      woman. DESIGN: Observational case report. METHODS: A 55-year-old woman sought
      treatment for a mass in the right upper eyelid. The lesion was excised twice
      previously, and recurred. The mass was reexcised and examined
      histopathologically. RESULTS: Light microscopy showed a cystic lesion lined by
      stratified squamous epithelium with a compact layer of eosinophilic keratin
      without granular cell layer. There was no atypia, mitosis, or stromal invasion.
      CONCLUSIONS: Although proliferating trichilemmal cyst shows benign
      histopathologic features, clinical manifestations may mimic those of more
      aggressive tumors with local recurrences or distant metastasis. Wide excision of
      the lesion and close long-term follow-up is recommended.

PMID- 17524786
TI  - Abnormal foveal avascular zone in nanophthalmos.
AB  - PURPOSE: To evaluate the foveas of nanophthalmic patients. DESIGN: Retrospective
      observational case series. METHODS: Four nanophthalmic patients examined between
      April 2005 and April 2006 were included. Visual acuity (VA), refractive
      correction, axial length, corneal diameter, presence or lack of foveal light
      reflex, as well as fluorescein angiograms (FAs), and optical coherence tomography
      (OCT) scans of the maculae were evaluated. RESULTS: None of the eight eyes had a
      foveal light reflex, corresponding to lack of a normal foveal pit on OCT.
      Fluorescein angiography showed no normal foveal avascular zones; all were either
      completely absent or small and rudimentary. CONCLUSIONS: Nanophthalmic patients
      rarely have best-corrected visual acuity (BCVA) better than 20/40 at any point in
      their lives, even with an absence of known complications, such as uveal effusion
      or glaucoma. In many patients, this visual deficiency may correspond to an absent
      or rudimentary foveal avascular zone and lack of a normal foveal pit.

PMID- 17524788
TI  - A prospective randomized clinical trial of phacoemulsification vs manual
      sutureless small-incision extracapsular surgery in Nepal.

PMID- 17524790
TI  - Incidence of intraoperative floppy iris syndrome in patients on either systemic
      or topical alpha1-adrenoceptor antagonist.

PMID- 17524791
TI  - Optical coherence tomography findings in acute retinal pigment epitheliitis.

PMID- 17524793
TI  - A modern classification of the exercise-related heat illnesses.
AB  - This article proposes a novel framework classification for the heat illnesses. It
      argues that heat stroke is the only described condition that is truly a "heat
      illness" since it is the only condition in which there is clear evidence for a
      pathological elevation of the core body temperature. If this is correct the non
      descript terms such as heat fatigue, heat exhaustion and heat syncopy should be
      removed from the modern lexicon. Since the evidence is that most cases of post
      exercise collapse are due to the development of postural hypotension immediately
      on the cessation of exercise, it is further proposed that more specific terms
      such as exercise-associated postural hypotension should be used, when
      appropriate, to replace the non-descript terms such as heat exhaustion, heat
      fatigue or heat syncopy. Furthermore this novel classification acknowledges that
      heat stroke may occur in some as a result of accelerated rates of endogenous heat
      production (thermogenesis). It also suggests that the elevated body temperature
      alone may not be the sole cause of fatal outcomes in heat stroke but that toxic
      chemicals released from damaged muscles by the processes causing this accelerated
      thermogenesis may also be involved.

PMID- 17524794
TI  - Author response to comments re "A systematic review of guidelines for the
      prevention of heat illness in community-based sports participants and officials".

PMID- 17524795
TI  - The effect of interstate travel on the sleep patterns and performance of elite
      Australian Rules footballers.
AB  - This study examined the effect of interstate travel on sleep patterns and game
      performance of elite Australian Rules footballers. Nineteen members of a Western
      Australian-based Australian Football League team participated in the study during
      the 2004 season. Sleep was assessed on the night before home and away games by
      measuring sleep duration (SLD), sleep efficiency (SLE), wake time (WT) and number
      of wakings (NW) via actigraphy. Subjective sleep quality was assessed using a
      sleep rating (SR) scale. Baseline sleep measurements were obtained over four
      consecutive non-game nights. Game performance was assessed using a coach's rating
      (CR) scale and impact ranking (IR) and by player statistics including frequency
      of possessions (P) and frequency of possessions and team assists (PTA). Compared
      to baseline, SLD was greater on the nights before home and away games (by 48 and
      39 min, respectively, p<0.05). Other sleep measures were unchanged. Sleep rating
      was poorer before away than home games (p<0.05). CR and IR were greater during
      home than away games (p<0.05). All other measures of performance were similar at
      home and away. These results show that prior interstate travel has minimal effect
      on sleep quality and game performance in elite footballers.

PMID- 17524796
TI  - Determinants of adherence to exercise in women treated for breast cancer.
AB  - We describe adherence to a three group randomised controlled trial that involved
      aerobic exercise therapy (N=34) and exercise-placebo intervention (N=36) or usual
      care (N=38) in women treated for breast cancer. We also investigated
      relationships between routes of trial recruitment, socio-economic
      characteristics, health behaviours, cancer treatment regimen(s) and subsequent
      adherence to the interventions. Women who had completed breast cancer treatment
      12-36 months previously were randomised to one of the groups. The intervention
      groups attended an exercise facility three times per week for eight weeks. A
      total of 77% of the aerobic exercise therapy and 88.9% of the exercise-placebo
      groups attended at least 70% of prescribed sessions. The percentage of women
      achieving 30min of aerobic exercise per session steadily increased during the
      intervention but many women were not able to achieve this goal. Routes of trial
      recruitment, socio-economic characteristics, health behaviours and cancer
      treatment regimen(s) were not related to intervention. Exercise therapy
      participants were able to comply with the progressive nature of the aerobic
      exercise intervention, although some women were not able to achieve 30min of
      aerobic exercise per session by intervention completion. Research is still
      required to tease out all the potential determinants of exercise in this
      population.

PMID- 17524799
TI  - Quality and Safety Education for Nurses.
AB  - Quality and Safety Education for Nurses (QSEN) addresses the challenge of
      preparing nurses with the competencies necessary to continuously improve the
      quality and safety of the health care systems in which they work. The QSEN
      faculty members adapted the Institute of Medicine(1) competencies for nursing
      (patient-centered care, teamwork and collaboration, evidence-based practice,
      quality improvement, safety, and informatics), proposing definitions that could
      describe essential features of what it means to be a competent and respected
      nurse. Using the competency definitions, the authors propose statements of the
      knowledge, skills, and attitudes (KSAs) for each competency that should be
      developed during pre-licensure nursing education. Quality and Safety Education
      for Nurses (QSEN) faculty and advisory board members invite the profession to
      comment on the competencies and their definitions and on whether the KSAs for pre
      licensure education are appropriate goals for students preparing for basic
      practice as a registered nurse.

PMID- 17524800
TI  - Current assessments of quality and safety education in nursing.
AB  - Concerns about the quality and safety of health care have changed practice
      expectations and created a mandate for change in the preparation of health care
      professionals. The Quality and Safety Education for Nurses project team conducted
      a survey to assess current levels of integration of quality and safety content in
      pre-licensure nursing curricula. Views of 195 nursing program leaders are
      presented, including information about satisfaction with faculty expertise and
      student competency development related to 6 domains that define quality and
      safety content: patient-centered care, teamwork and collaboration, evidence-based
      practice, quality improvement, safety, and informatics. With competency
      definitions as the sole reference point, survey respondents indicated that
      quality and safety content was embedded in current curricula, and they were
      generally satisfied that students were developing the desired competencies. These
      data are contrasted with work reported elsewhere in this issue of Nursing Outlook
      and readers are invited to consider a variety of interpretations of the
      differences.

PMID- 17524801
TI  - Integrating quality and safety content into clinical teaching in the acute care
      setting.
AB  - Teaching the highest quality and safest practice has long been a goal of faculty
      members in pre-licensure nursing education programs. This article will describe
      innovative approaches to integrating quality and safety content into existing
      clinical practica. The core competencies identified by the Quality and Safety
      Education for Nurses project--patient-centered care, teamwork and collaboration,
      evidence-based practice, quality improvement, safety, and informatics--serve as
      the framework for the teaching/learning exercises. The strategies described
      require a shift in attention rather than changes in course content and can be
      included in any clinical rotation in an acute care setting.

PMID- 17524802
TI  - Promoting interprofessional education.
AB  - The work of the Institute of Medicine and others has clearly demonstrated that
      when healthcare professionals understand each others' roles and are able to
      communicate and work effectively together, patients are more likely to receive
      safe, quality care. Currently, there are few opportunities to bring faculty and
      students in pre-licensure programs from multiple disciplines together for the
      purpose of learning together about each others' roles, and practicing
      collaboration and teamwork. Designing and implementing interprofessional
      education offerings is challenging. Course scheduling, faculty interest and
      expertise in interprofessional education (IPE), a culture of IPE among faculty
      and students, and institutional policies for sharing course credit among schools
      are just a few of the challenges. This article explores the concept of IPE, and
      how faculty in schools of nursing might take the lead to work with colleagues in
      other health profession schools to prepare graduates to understand each others'
      roles, and the importance of teamwork, communication, and collaboration to the
      delivery of high quality, safe patient care.

PMID- 17524803
TI  - Quality and safety curricula in nursing education: matching practice realities.
AB  - Health care delivery settings are redesigning in the wake of staggering reports
      of severe quality and safety issues. Sweeping changes underway in health care to
      address quality and safety outcomes lend urgency to the call to transform nursing
      curricula so new graduate competencies more closely match practice needs.
      Emerging views of quality and safety and related competencies as applied in
      practice have corresponding implications for the redesign of nursing education
      programs. Nurse executives and nurse educators are called to address the need for
      faculty development through strategic partnerships.

PMID- 17524804
TI  - Quality and safety education in nursing: more than new wine in old skins.

PMID- 17524805
TI  - Cystic fibrosis: a disease of vulnerability to airway surface dehydration.
AB  - Cystic fibrosis (CF) lung disease involves chronic bacterial infection of
      retained airway secretions (mucus). Recent data suggest that CF lung disease
      pathogenesis reflects the vulnerability of airway surfaces to dehydration and
      collapse of mucus clearance. This predisposition is caused by mutations in the CF
      transmembrane conductance regulator (CFTR) gene, resulting in (i) the absence of
      CFTR-mediated Cl- secretion and regulation of epithelial Na+ channel (ENaC)
      function; and (ii) the sole dependence on extracellular ATP to rebalance these
      ion transport processes through P2 purinoceptor signaling. Recent clinical
      studies indicate that inhalation of hypertonic saline osmotically draws
      sufficient water onto CF airway surfaces to provide clinical benefit.

PMID- 17524806
TI  - Sources and sinks: revisiting the criteria for identifying reservoirs for
      American cutaneous leishmaniasis.
AB  - Molecular-based approaches might be misleading for assessing the 'potential
      importance' of possible reservoirs for parasites unless used in conjunction with
      population dynamics and ecological studies that provide an understanding of the
      linkages between the enzootic transmission cycle (in wild animals) and that in
      domestic animals. Better understanding of ecological constraints on Leishmania
      transmission is needed to assess fully the passage of the parasite between its
      sandfly vector and different mammalian host species. We use a straightforward
      mathematical framework to illustrate that misuse of association patterns, as
      guidance for implementation of control measures, can in fact increase the
      endemism of leishmaniasis.

PMID- 17524807
TI  - Biomarkers of treatment response in clinical trials of novel antituberculosis
      agents.
AB  - Global initiatives have been launched to develop improved tuberculosis
      chemotherapy. New drugs and potential treatment-shortening regimens require
      careful assessment in clinical trials, but existing markers of treatment outcome
      clinical cure and relapse-require prolonged follow-up of patients. There is,
      therefore, a need to find alternative biomarkers or surrogate endpoints
      predictive of response. Effective treatment requires drugs with sterilising
      activity to produce clinical cure without relapse, and thus a useful biomarker
      for a drug under trial must predict the likelihood of relapse. We explore the
      strengths and weaknesses of existing biomarkers, which assess either host
      response or mycobacterial load. Change in mycobacterial burden is likely to be
      the best indicator of treatment outcome, but the optimum study techniques remain
      undefined. Finally, we propose methods to assess candidate markers, and how these
      candidate markers could be implemented in future clinical trials.

PMID- 17524808
TI  - Unique characteristics of NK cells throughout the human female reproductive
      tract.
AB  - In this study, we have analyzed the presence and subsets of NK cells throughout
      the tissues of the FRT. We demonstrate that there are NK cells in the various FRT
      tissues and that their phenotype and regulation are largely dependent upon the
      FRT tissue where they reside. NK cells in the Fallopian tube, endometrium,
      cervix, and ectocervix expressed CD9 while blood NK cells did not. We have also
      found that unique subsets of NK cells are in specific locations of the FRT. The
      NK cells in the lower reproductive tract did not express CD94, but they did
      express CD16. In contrast, NK cells in the upper FRT express high amounts of CD94
      and CD69, but few NK cells expressed CD16. All of these FRT NK cells were able to
      produce IFN-gamma upon stimulation with cytokines. Furthermore, the number of NK
      cells varied with the menstrual cycle in the endometrium but not in the cervix or
      ectocervix. These data suggest that unique characteristics of the tissues may
      account of specific localization of different NK cell subsets.

PMID- 17524809
TI  - Identification of insulin autoantibodies of IgA isotype that preferentially
      target non-human insulin.
AB  - Insulin autoantibodies (IAA) precede clinical type 1 diabetes in children.
      Immunization events leading to IAA are unknown. The aim of this study was to
      determine whether some IAA result from mucosal immunization. IgA-IAA and binding
      of IAA to non-human insulin were examined in selected high and low affinity IAA
      positive samples and in first IAA-positive samples from children aged <2 years.
      High affinity IAA (>10(9)L/mol) bound strongly to human insulin and poorly to
      chicken insulin. In contrast, 12/13 lower affinity IAA were chicken insulin
      reactive, binding equally to human and chicken insulin (n=4), or preferentially
      binding chicken insulin (n=8). IgA-IAA were found in association with chicken
      insulin-reactive IAA, and included cases where IgA-IAA predominated over IgG-IAA.
      Among 20 IAA-positive children aged <2 years, one had early IgA-chicken insulin
      reactive IAA that were replaced by high affinity IgG-IAA. The findings suggest
      that some IAA can result from immunization against molecules other than human
      insulin at mucosal sites.

PMID- 17524812
TI  - Transplantation research in Iran: a bibliometric study.
AB  - BACKGROUND: Scientific articles are indicators of research interest and efforts
      in every country. The aim of the current study is to describe the characteristics
      of the transplantation-related research efforts with respect to the domestic
      published works in Iran between 1993 and 2003. MATERIALS AND METHODS: In a
      descriptive design, we searched IranMedex (Iranian database for indexing medical
      articles; available at: http//www.iranmedex.com) for all the biomedical articles
      published between 1993 and 2003 in 91 Iranian journals. The search was conducted
      using "transplantation" and "transplant" as key words. A printed copy of the
      references was reviewed individually so as to identify the transplanted organ,
      study design, number of authors, and type of article. RESULTS: Among 11371
      articles, 545 (4.8%) were related to transplantation. An increasing trend was
      observed in the number of publications from 1993 to 2003. Most articles were
      published in Farsi (90%). The most frequently published articles were original
      articles (84.4%). The main subjects of were kidney (61.7%), followed by liver
      (12%) and bone marrow transplantation (10.8%). Cornea was the topic of research
      in only 3% of the papers. Of all manuscripts, 9.5% consisted of clinical trials.
      The mean number of authors was 3.6 +/- 2.2 (1 to 14). CONCLUSIONS: Iranian
      researchers seem to be interested in the topic of transplantation; however, some
      fields of transplantation are neglected. This pooling of valuable information can
      be used by other countries, especially by researchers from the Middle East
      Society for Organ Transplantation region. Such databases could form an invaluable
      network for an exchange of experience in the region to solve common problems.

PMID- 17524813
TI  - Improving the organ transplantation program in Greece: institution of local
      transplant coordinators' network.
AB  - The success of a transplantation program depends upon the quality and
      effectiveness of the donation process, whereby the key role is assigned to the
      local transplant coordinator (TxC). This important professional figure was only
      recently established in Greece. The local TxC duties were outlined alongside
      those of the Hellenic Transplant Organization (HTO) foundation in 1999, whereby
      three different transplant coordinator positions--central, local, and clinical-
      were specified. In 2002, the above-mentioned positions were legally consolidated.
      Local TxCs had to be doctors or nurses, in a 70%-30% ratio, already working in
      intensive care unit (ICU) and had to be appointed by the hospital and ICU
      directors in each hospital as requested by the HTO. By the end of 2004, this
      network consisted of 122 TxCs located in 74 ICUs, especially trained in donation
      procedures and ethics. Half of the doctors were ICU directors, especially
      appointed to influence ICU personnel. Furthermore in 2005, the board of directors
      of HTO decided that there should be closer cooperation between the 45 most donor
      generating ICUs and their TxCs. It was decided that the local TxCs would work
      part-time and receive a monthly grant. The 45 ICU network started in 2005,
      resulting in an 154% increased rate of potential donor referrals and a 33% and
      almost 38% increase in actual donors and transplantations, respectively, compared
      to 2004. This substantial increase was achieved by the institution of TxC
      network.

PMID- 17524814
TI  - Substantial increase in cadaveric organ transplantation in Greece for the period
      2001-2005.
AB  - The Hellenic Transplant Organization (HTO), a nonprofit organization sector of
      the Greek Ministry of Health, was officially established in 1999. Since March
      2001, HTO has been responsible for donation and transplantation processes in
      Greece and organ sharing between Greece and other European countries. The
      organization's main tasks are: donor referral, charting, donor assessment, organ
      evaluation, organ allocation and transplantation. Today, the results show
      increased success rates to previously believed unthinkable levels. Precisely, the
      percentage of referred versus used cadaveric donors increased by 468% and 134%,
      respectively. Cadaveric kidney transplantation has also shown remarkable progress
      with a 126% increase during the same period. Similarly, liver transplantation
      showed a threefold rise (89%) during the same time. Unfortunately, heart and lung
      transplantations remain low, thus preventing statistical conclusions to be drawn.
      Although Greece in previous years had the lowest donor and transplantation rates
      per million population, its position compared with other European countries is
      expected to rise significantly this year. Undoubtedly, the numbers and
      percentages compared to previous years are due to the radical changes implemented
      by the HTO, by introducing transplant coordination principles and procurement
      management, which were concepts not previously established in Greece. However,
      there are still major obstacles, such as intensivists' refusal to disconnect,
      inaccessible geographical locations, few transplant centers, and society's
      suspicion of organ donation concept, that still need attention. Nevertheless, the
      first step has been taken and other European countries standards will hopefully
      be attained soon.

PMID- 17524815
TI  - Foundation of local network for increasing organ donation in southern Iran.

PMID- 17524816
TI  - Donor gender balance in a living-related kidney transplantation program in Oman.
AB  - It has been observed in several Eastern and Western countries that there is a
      gender imbalance among kidney donors. In the international experience,
      approximately 65% of live kidney donors have been women. We retrospectively
      studied the distribution of female and male donors or recipients among living
      kidney transplantations performed from 1980 to 2005, namely 198 Omani recipients
      of living-related kidney transplantations. To examine cultural influences,
      transplantations performed or expatriates were excluded from the study. For the
      whole period, 98 out of 198 donors (49.5%) were women. The number of female
      recipients 75 of 198 (38%) versus males were 123 (62%) recipients. We then
      subdivided the period into three intervals: 1980 to 1990, 1991 to 2000, and 2001
      to 2005. The numbers of female donors for these three periods were 29 of 64
      (45%), 42 of 89 (47%), and 27 of 45 (60%), respectively. There was a persistent
      preponderance of male recipients ranging from 58% to 66% during these periods. We
      concluded that there was no gender imbalance for kidney donors. Nevertheless,
      there was a male preponderance in the recipient group.

PMID- 17524817
TI  - Laparoscopic donor nephrectomy: single-center experience in Egypt with 400
      consecutive cases.
AB  - INTRODUCTION: In this study, we present our experience with laparoscopic donor
      nephrectomy and evaluate the outcomes of donors and recipients. PATIENTS AND
      METHODS: Between March 2003 and August 2006, 400 laparoscopic donor nephrectomies
      were performed in our institution. Donors were evaluated for renal vasculature
      using computed tomography angiography. We used the left kidney in 329 donors and
      the right kidney in 71. Donor surgeries were done transperitoneally using three
      trocars on the left side and four trocars on the right side. Kidneys were
      extracted manually through a 7-cm Pfanenstiel incision. RESULTS: All cases were
      completed laparoscopically. Mean operative time was 117 +/- 34 minutes. Mean
      blood loss was 56 +/- 28 mL. None of the donors required a blood transfusion.
      Mean warm ischemia time was 2.6 +/- 0.4 minutes. The mean renal artery length was
      3.1 +/- 0.4 cm; the mean renal vein length was 2.4 +/- 1.2 cm. Mean hospital stay
      was 2.1 days. No donor required readmission. Kidneys were transplanted
      successfully and the mean recipient creatinine on discharge was 1.2 +/- 0.6
      mg/dL. One patient had a renal artery thrombosis on postoperative day 2. Another
      patient with double renal arteries had thrombosis of the smaller artery just
      after surgery. Acute tubular necrosis was seen in 17 patients, four of whom
      required dialysis. Kidney function recovered thereafter in all acute tubular
      necrosis cases. CONCLUSION: Laparoscopic surgery is a minimally invasive approach
      for living donor nephrectomy with good functional outcomes. The donor benefits
      from lesser morbidity without compromising the anatomic or physiological outcome
      of the nephrectomized kidney.

PMID- 17524818
TI  - Laparoscopic donor nephrectomy for pediatric recipient.
AB  - INTRODUCTION: To present our outcome of laparoscopic donor nephrectomy for
      pediatric recipients, who may pose special challenges. MATERIALS AND METHODS:
      Since March 2003, we performed more than 400 laparoscopic donor nephrectomies for
      39 pediatric recipients (age less than 17 years of age). The preoperative,
      intraoperative, and postoperative data were reviewed to analyze the outcomes of
      these cases. We used the left kidney in 26 and the right kidney in 13 cases.
      Seven cases had double renal arteries, which were reconstructed on the bench.
      RESULTS: The mean donor and recipient ages were 31 +/- 5 years and 13 +/- 4
      years, respectively. The mean donor operative time was 2.1 hours (range 1.2 to
      3.2). The warm ischemia time averaged 3 +/- 0.6 minutes. In 27 cases, we used the
      common iliac artery and common iliac vein for vascular anastomosis. In 12 cases,
      the anastomosis was performed to the aorta and vena cava. Seven patients had
      prior augmentation cystoplasty, and the ureter was anastomosed to the pouch
      directly. All grafts functioned immediately, with a mean creatinine at 24 hours
      of 1.5 +/- 0.3 mg/dL. At last follow-up (mean 13.6 months), the mean creatinine
      was 0.9 mg/dL. One patient lost the graft due to severe rejection that was
      resistant to antithymocyte globulin. CONCLUSIONS: Laparoscopic donor nephrectomy
      for pediatric recipients is safe and provides quality organs with excellent
      function. Outcome is comparable to those after open donor nephrectomy.

PMID- 17524819
TI  - Kuwait experience in laparoscopic donor nephrectomy: first 80 cases.
AB  - INTRODUCTION: Laparoscopic donor nephrectomy (LDN) has been adopted rapidly as it
      offers less postoperative pain, early recovery, and better cosmetic results
      compared with the open approach. This prospective study investigated the results
      of the first 80 LDN performed between May 2005 and May 2006, with regard to donor
      morbidity and effect on graft function. PATIENTS AND METHODS: LDN was attempted
      in 80 donors by one surgical team. Donors included 68 men and 12 women, ages 22
      to 53 years, with body mass indices of 17.9 to 42.4. According to computed
      tomographic angiography, left nephrectomy was planned in 75 donors and right
      nephrectomy in 5. RESULTS: LDN was completed successfully in 74 (92.5%) and
      converted to open in 6 (7.5%) secondary to technical difficulties and operative
      bleeding. The mean operating time for LDN was 186.16 minutes (range, 95-260
      minutes). Mean warm ischemia time (WIT) was 5.7 minutes (range 2-16 minutes).
      Mean hospital stay was 5.28 days (range, 3-14 days). Two donors (2.5%) were
      reexplored for postoperative bleeding. Renal function in all donors was
      satisfactory within 3 months of surgery. Immediate diuresis occurred in 76 (95%)
      recipients. Acute cellular rejection was diagnosed in 1 recipient. No association
      was observed between WIT, graft function, development of acute tubular necrosis
      (ATN), or rejection. Plasma creatinine normalization was clearly associated with
      donor age. CONCLUSIONS: LDN was found to be a safe procedure with low
      postoperative morbidity and short recovery time for donors. It can potentially
      increase the donor pool.

PMID- 17524820
TI  - Color Doppler findings in transplanted kidneys and remnant kidneys of donors 6 to
      12 months after kidney transplantation.
AB  - OBJECTIVES: Ultrasonography and color Doppler have been used extensively in the
      evaluation of transplanted kidney. The aim of this study was evaluation and
      comparison of color Doppler sonography findings in the remnant kidney of living
      donors and the transplanted kidney at 6 to 12 months after kidney
      transplantation. METHODS: In a cross-sectional study we evaluated
      ultrasonographic (US) and color Doppler findings in 20 kidney allograft recipient
      and donors. Group 1 were unrelated and related kidney donors, and group 2,
      allograft recipients. Color Doppler US was performed by one sonologist on the
      remnant kidney of the living donor and the transplanted kidney of the recipient
      at 6 to 12 months after kidney donation and transplantation. We recorded, kidney
      size (including length and anteroposterior diameter), cortical thickness,
      resistive index (RI), and pulsatile index (PI). Statistical analysis was
      performed using SPSS 13 win (t test) for comparison of the results in donors and
      recipients. All data are presented as mean values +/- SD with P values less than
      .05 considered significant. RESULTS: In group 1, mean age of kidney allograft
      recipients was 39.92 +/- 11.95 years with male-to-female ratio of 1/2. Mean
      length, width, and cortical thickness of the transplanted kidney were 120.15 +/-
      11.95 mL, 53.65 +/- 7.50 mL, and 8.53 +/- 1.00 mL, respectively. Mean RI and PI
      were 0.60 +/- 0.08 and 1.02 +/- 0.23, respectively. Mean serum creatinine was
      1.23 +/- 0.24 mg/dL. Mean duration of renal transplantation was 7.27 +/- 1.10
      months. In group 2, mean age of recipients was 25.63 +/- 3.50 years with male-to
      female ratio of 1/10. Mean length, anteroposterior diameter, and cortical
      thickness were 120.77 +/- 9.28 mL, 53.36 +/- 4.52 mL, and 9.04 +/- 1.27 mL,
      respectively. Mean RI and PI were 0.60 +/- 0.02 and 1.07 +/- 0.13, respectively.
      There was no significant difference in the length, anteroposterior diameter,
      cortical thickness, RI, and PI of donors and transplanted kidneys at 6 to 12
      months after transplantation (P>.05). There was a significant increase in both
      donor and recipient kidney size at 6 to 12 months after transplantation (P<.05).
      CONCLUSION: It seems that renal US and Doppler parameters remain stable in the
      recipient and donor at least upon short-term evaluation. Long-term study with
      more patients is recommended.

PMID- 17524821
TI  - Attitude of Iranian nephrologists toward living unrelated kidney donation.
AB  - Living unrelated kidney donation (LURD) is increasing worldwide due to the
      shortage of cadaveric kidneys. In our country an LURD program has been practiced
      since 1988. This study sought to evaluate the attitude of Iranian nephrologists
      towards various aspects of the program. Questionnaires including 20 queries were
      sent to nephrologists. Among 100 randomly selected nephrologists, 50 completed
      and returned the questionnaires. Forty six (92%) and 45 (90%) believed that LURD
      has potential minor short- and long-term complications, respectively. Forty two
      percent assumed renal failure was a potential complication. Ninety two percent
      used to inform donors about the complications, all verbally. Thirty four percent
      and 72% assumed inhalational opium addiction and heroin addiction were
      contraindications to LURD, respectively. Twenty eight percent and 68% believed
      that the amount of recipients' gift and the governmental award are not
      sufficient, respectively. Thirty two percent believed that all compensation
      should be paid by the government. Sixty six percent believed that donors should
      be given social advantages, and 26% believed that they should not, in order to
      not enhance persuasion of nonaltruistic donation. Eighty eight percent claimed
      that donor follow-up is not regularly done and should be organized. Finally, 30
      agreed and 19 disagreed with LURD. We conclude that despite the success of our
      LURD program in elimination of the transplant waiting list, most Iranian
      nephrologists believe that there should be some revisions. Verbal information
      about complications may not be sufficient to help the donors to make a correct
      decision. We should reconsider the method and amount of financial compensation
      and organize a regular follow-up program.

PMID- 17524822
TI  - Is living kidney donation really safe?
AB  - OBJECTIVE: Living donor kidney transplantation (LDKT) yields the best results of
      all renal replacement therapies in terms of patient and graft survival. It is the
      main method in many countries because of worsening patient outcomes due to the
      accumulation of aged patients with long periods on dialysis and no possibility to
      increase the number of cadaver donor transplantations. Because of concerns
      dealing the risks inflicted on the donors, we sought to evaluate the long-term
      complications of LDKT. PATIENTS AND METHODS: We evaluated over 3 years 86 living
      kidney donors (58 men, 28 women) whose procedures were >1 year ago. The mean time
      postoperatively was 17.24 +/- 5.04 months and their mean age, 28.97 +/- 4.75
      years. Basic information regarding current health status, including physical
      examination and blood pressure as well as serum urea, creatinine serum albumin,
      blood glucose, lipid profile, urinanalysis, and 24-hour urine protein were
      evaluated every 6 months after donation. Also an ultrasound of the kidney,
      urinary tract, and testis was performed at these times. RESULTS: Donor
      nephrectomies were left sided in 60 (69.8%) cases and right sided in 26 (30.2%)
      cases. The majority of the donors (n=80) were unrelated (93%). There was a total
      complication rate of 54.6%. The most common complication was hypertension
      (37.5%). Serious complications occurred in five cases (5.8%). In six (6.9%) the
      patients serum creatinine was >or=1.4 mg/dL. Microalbuminuria was found in 10.4%;
      hematuria in 13.9%; pyuria in 8.1%; and renal stone in 6.9%. Varicocele was found
      in 24.1% of male patients (23.3% of patients who had left nephrectomised).
      Persistent pain was reported by 44.1%. Antidepressants were prescribed to 9.3% of
      donors because of severe depression. CONCLUSION: Living kidney donation is not so
      safe and has some late complications. Precise predonation evaluation and long
      term follow-up of kidney donors for detection and prevention of complications is
      necessary.

PMID- 17524823
TI  - Socioeconomic status of Iranian living unrelated kidney donors: a multicenter
      study.
AB  - Renal transplantation is the best treatment modality for end-stage renal disease
      (ESRD) patients. In Iran, a living unrelated donor (LURD) transplant program was
      started in 1988, because of the shortage of living related and cadaver donors. In
      this study, we evaluated the socioeconomic status of LURD in Iran. We enrolled
      478 LURDs from 30 transplant centers between October 2005 and March 2006. The
      demographic data, education, employment, motivation, and satisfaction status were
      asked. Economic status was assessed using criteria of the statistics center of
      Iran. Ninety-six percent of donors were referred from the Kidney Foundation of
      Iran (KFI). The mean age of the donors was 27 +/- 4.8 years and 85% were men
      (n=408). Fifty-one percent were smokers, 82% married, and 79% the breadwinner;
      29% were unemployed; 2.7%, 90.8%, and 6.5% were illiterate, school graduates, and
      university graduates, respectively. Coercion was documented for only one donor.
      Financial issues were the most frequent motive. Among them, 91% were satisfied
      with the donation. Finally, 53% suggested kidney donation to others. Of donors,
      62% were living below the poverty line. In the Iran model, the KFI is a bridge
      that connects recipients and donors. As a result, there is no middle man or
      broker introducing donors to recipients. The transplantation team knows nothing
      about money transactions between recipient and donor. Most donors were satisfied
      with the donation. However, establishment of a government-regulated program for
      social support of donors, such as lifelong health insurance may be a compensation
      for donors.

PMID- 17524824
TI  - Right hepatic lobe donation: impact on donor quality of life.
AB  - The aim of this study was to assess the impact of living-donor liver
      transplantation on the donor's quality of life. Among the 48 performed at our
      hospital from October 2003 to June 2006, 46 (27 men, 19 women; mean age, 37.4
      years) were followed for more than 4 months (mean, 16.5+/-8 months). In April
      2006, these donors participated in a survey that included medical and
      psychosocial outcomes. Seven complications occurred in four of 46 donors (8.6%):
      two biliary leaks, two wound infections, one incisional hernia, one portal vein
      thrombosis, and one deep venous thrombosis. For the donor with portal vein
      thrombosis, the vein was recanalized, and she recovered without treatment; a bile
      leak from the cut liver surface and an incisional hernia also developed in the
      same donor. The biliary leak was treated with percutaneous drainage, and the
      incisional hernia was repaired surgically. Fifteen donors were housewives, 31
      worked outside the home, and 94% returned to their work. A change in body image
      was reported in 4.3% of the donors. None reported impaired sexual function.
      Complete recovery occurred in 86% of donors, 94% of the donors said that they
      would donate again if necessary, and 97% believe that they had benefited from the
      donation experience. In conclusion, almost all donors were able to return to
      their prior jobs within a few months of surgery, and most donors were satisfied
      with the donation procedure.

PMID- 17524825
TI  - Donor outcome after living liver donation: a single-center experience.
AB  - OBJECTIVES: To objectively evaluate outcomes after living donor hepatectomy.
      PATIENTS AND METHOD: Between November 2002 and August 2006, a total of 44
      procedures were performed (35 right, eight left, and one aborted after surgical
      incision). The Clavien classification was used to record surgical complications
      as follows: grade I, alterations from the ideal postoperative course not
      requiring specialized pharmacological or surgical treatment; grade II,
      complications requiring specialized pharmacological treatment, blood transfusion,
      or total parental nutrition; grade III-a, complications requiring invasive
      intervention without general anesthesia; Grade III-b, requires general
      anesthesia; Grade IV-a, single organ dysfunction; Grade IV-b, multiorgan
      dysfunction; grade V, death; The suffix "d" indicated disability. In this study,
      grades I and II complications were considered minor, while grades III and V and
      any lasting disability, serious complications. RESULTS: Male/female ratio was
      34/10; median age was 25 years (range, 18 to 42); median hospital stay was 6 days
      (range, 4 to 14); and only two donors required intraoperative blood transfusion.
      After a median follow-up of 529 days (range, 8 to 1354), a total of 28
      morbidities were encountered in 17 donors (38.6%), including nine donors (20.4%)
      who had serious complications. Among the 28 donor morbidities, 18 were grade I
      complications; three were grade III-a complications; five were grade III-b
      complications; and two were grade IV-a complications. No death was encountered in
      our experience. CONCLUSIONS: In our experience, donor hepatectomy was not an
      entirely safe procedure; therefore, extreme care should always be given by the
      transplant teams to living donors to avoid any distressing morbidity or even, the
      less likely but more catastrophic, mortality.

PMID- 17524826
TI  - Effect of the interval between organ donor brain death and organ harvesting on
      kidney graft function after transplantation.
AB  - We hypothesized that providing a longer resuscitation period (>12 hours) for a
      brain-dead organ donor (BDOD) to attenuate the detrimental effects of sympathetic
      discharge that occur during this event would improve graft function. We reviewed
      the medical records of patients who had received a kidney transplant from a BDOD
      between November 2001 and June 2006. The patients were divided into two groups
      according to whether the interval between the brain death of the organ donor and
      organ harvest was >12 hours (group 1 n=12) or <or=12 hours (group 2 n=11). The
      BDODs for the patients in the two groups displayed similar blood urea nitrogen
      (BUN) and creatinine levels during the interval between brain death and organ
      harvest. The graft recipients showed similar levels of serum creatinine. BUN, and
      urine output at baseline and on postoperative day 1 (P>.05). When compared with
      patients in group 2, those in group 1 demonstrated a significant trend toward
      improved renal graft function in terms of serum creatinine levels, BUN levels,
      and urine output. Five patients in group 2 and two patients in group 1 required
      hemodialysis during the early posttransplantation period (P>.05). Our results
      indicate that longer in situ resuscitation of the graft kidney in BDODs may
      improve posttransplant function.

PMID- 17524827
TI  - Pretransplantation systolic blood pressure and the risk of delayed graft function
      in young living-related renal allograft recipients.
AB  - Delayed graft function (DGF) is associated with decreased long-term renal
      allograft survival, however, the entire mechanism of action of DGF has not yet
      been established. The goal of this study was to determine possible risk factors
      for DGF in young living-related renal allograft recipients. We retrospectively
      analyzed the outcome of 142 renal transplant recipients (115 men and 27 women;
      mean age, 29.7 +/- 9.43 years; 114 living-related donors and 28 cadaveric
      donors). Data recorded for each patient and donor included gender, age at
      transplantation, duration of pretransplantation dialysis (recipients only), body
      mass index, number of human leucocyte antigen mismatches, panel-reactive
      antibodies, donor creatinine clearance, body weight, systolic and diastolic blood
      pressure levels, lipid profile, and biochemical parameters. Having obtained the
      transplant from a cadaveric donor (P<.000, odds ratio [OR]=17.556, confidence
      interval [CI]=5.961-51.743) and a pretransplantation systolic blood pressure
      level in the recipient of <120 mm Hg (P<.021, OR=3.600, CI=1.214-10.672) were
      possible risk factors for DGF. When only living-related recipients were
      considered, the systolic blood pressure level was significantly associated with
      DGF. We concluded that a pretransplantation systolic blood pressure level <120 mm
      Hg is a risk factor for DGF and that preoperative blood pressure control and
      intervention may help to decrease the risk of DGF.

PMID- 17524828
TI  - The incidence and risk factors of delayed graft function in 689 consecutive
      living unrelated donor renal transplantation.
AB  - Due to the severe shortage of deceased donor kidneys, the number of renal
      transplantation from living-related and living-unrelated donors has increased
      worldwide. The incidence and risk factors of delayed graft function after
      deceased donor renal transplantation have been extensively studied. In this
      analysis, the incidence and predictors of delayed graft function was investigated
      in 689 living-unrelated kidney recipients. In 53 recipients, dialysis was needed
      within the first week after renal transplantation (7.7%). The risk factors for
      delayed graft function upon univariate analysis models were: female gender of
      kidney donor (P=.027), renal allograft with multiple arteries (P=.005) and
      previous transplantation (P<.005). Upon multivariate analysis, the only risk
      factor for development of delayed graft function was retransplantation (P=.001).

PMID- 17524829
TI  - Influence of perioperational acid-base balance disorders on early graft function
      in kidney transplantation.
AB  - INTRODUCTION: Reperfusion is a crucial moment in kidney transplantation,
      connected with many metabolic changes that are the result of preservation and
      intraoperative course including ion movements, free radical generation, ATP and
      other adenylate depletion. During reperfusion we observed increased metabolic
      acidosis, which may be the result of accumulation of lactic acid due to anaerobic
      metabolism, with a simultaneous expiratory pCO(2) growth as respiratory
      compensation. The study's purpose was to examine acid-base balance dynamics
      during 30 minutes of reperfusion of the transplanted kidney and its influence on
      renal function based on observations of the 1-year creatinine values. MATERIALS
      AND METHODS: The examined group consisted of 76 recipients: 44 men, 32 women.
      Measurements by gasometric analysis and expiratory pCO(2) in each patient were
      performed nine times during reperfusion. In the postoperative period we analyzed
      donor-related factors including: gender, age, number of HLA matches weight and
      height, as well as recipient-related factors including: gender, age, basic
      immunosuppression, creatinine level at hospital discharge and at 5 to 24 months
      of follow-up. Statistical significance was analyzed using repeated-measures
      analysis of variance followed by Tukey post hoc test as well as Mann-Whitney U
      and Spearman's correlation tests. RESULTS: The analysis showed correlations
      between reperfusion, acidosis, respiratory pCO(2) compensation, early graft loss,
      patient death, donor and recipient gender, renal function, donor age, and
      histocompatibility. CONCLUSIONS: At the beginning of reperfusion there is
      increasing metabolic acidosis with simultaneous expiratory pCO(2) as
      compensation. A greater relative increase in expiratory air pCO(2) was correlated
      with a higher incidence of early graft loss. The higher intensity of metabolic
      acidosis correlated with worse renal function at 6 months after transplantation.
      Elderly donor age and fewer HLA-matched antigens correlated with greater
      intensity of metabolic acidosis during 30 minutes of kidney reperfusion.

PMID- 17524830
TI  - Association of hyperglycemia on allograft function in the early period after
      renal transplantation.
AB  - Hyperglycemia is common following renal transplantation. This study was conducted
      to evaluate the relationship of perioperative serum glucose levels and acute
      rejection in 100 nondiabetic patients who underwent renal transplantation. Blood
      glucose was measured immediately following surgery and every 6 hours during the
      first 48 hours posttransplant as well as for 1 month to evaluate occurrence of
      acute rejection episodes (ARE). The rate of ARE was 33%. The mean blood glucose
      level immediately after surgery in patients with versus without ARE was 249.67 +/
      61.78 and 184.82 +/- 73.35 mg/dL, respectively (P=.000). There was no
      significant correlation between ARE and donor or recipient age or sex, delayed
      graft function, type of donor, or treatment. This study suggested a correlation
      between immediate blood glucose and ARE. In this regard, blood glucose monitoring
      and control during operation and immediate postoperatively may reduce the acute
      rejection rate.

PMID- 17524831
TI  - Ischemia/reperfusion of the liver induces heart injury in rats.
AB  - OBJECTIVE: We evaluated the cardiovascular injury induced by ischemia and
      reperfusion (I/R) of the liver by measuring changes in blood levels of cardiac
      troponin I (cTNI), an index of cardiovascular injury, as well as levels of
      selected indicators of an inflammatory response. MATERIALS AND METHODS: Ischemia
      was induced in the rat liver by clamping the common hepatic artery and portal
      vein for 40 minutes, after which flow was restored, and the liver reperfused for
      90 minutes. Blood samples were collected prior to ischemia and after reperfusion.
      cTNI as well as levels of tumor necrosis factor alpha (TNFalpha), hydroxyl
      radical (.OH), nitric oxide (NO), and alanine transferase (ALT) were measured.
      RESULTS: I/R of the liver induced a significant increase in ALT (P<.001).
      Increased cTNI levels (P<.05) were associated with inflammatory responses, such
      as elevated levels of TNFalpha (P<.001), . OH (P<.001), and NO (P<.001). After
      administration of 3-aminobenzamide, a poly(ADP-ribose) polymerase (PARP)
      inhibitor, liver and heart injuries were significantly attenuated (P<.05).
      CONCLUSIONS: I/R-induced liver injury was associated with cardiovascular injury,
      perhaps resulting from inflammatory responses triggered by elevated levels of
      reactive radical species of nitric oxide, superoxide, and peroxynitrite, by which
      PARP was activated. 3-Aminobenzamide, significantly attenuated I/R-induced liver
      and heart injuries.

PMID- 17524832
TI  - Reperfusion liver injury-induced superoxide dismutase and catalase expressions
      and the protective effects of N-acetyl cysteine.
AB  - AIM: Reperfusion of the ischemic liver results in the generation of oxygen
      radicals. In this study, we analyzed if the mRNA and protein expressions of
      superoxide dismutase (SOD) and catalase increased after ischemia (I) and
      reperfusion (R) of the rat liver. MATERIALS AND METHODS: Ischemia was induced by
      clamping off the common hepatic artery and portal vein of rats for 40 minutes,
      which were then reperfused for 90 minutes. Blood samples collected prior to I and
      after R were analyzed for hydroxyl radical (.OH), nitric oxide (NO), and alanine
      transferase (ALT). Liver tissues were used to analyze the SOD and catalase mRNA
      and protein expressions by real-time polymerase chain reaction and Western blot.
      RESULTS: The results showed that this protocol resulted in elevation of the blood
      ALT, NO, and .OH levels (P<.001). mRNA (P<.01) and protein expressions (P<.05) of
      SOD and catalase were all increased. Pretreatment with antioxidant, N-acetyl
      cysteine, attenuated the liver injury. CONCLUSION: These results indicate that
      reperfusion of the ischemic liver induced antioxidant enzymes expressions so that
      oxygen radicals are scavenged. Oxygen radical scavenger could further attenuate
      the I/R-induced liver injury.

PMID- 17524833
TI  - Translocation of pancreatic juice after ischemia and reperfusion of the
      intestines and the effects of gabexate mesilate (FOY) in rats.
AB  - OBJECTIVES: To evaluate pancreatic juice translocation after ischemia and
      reperfusion (I/R) of the superior mesenteric artery (SMA). METHODS: Ischemia was
      induced by clamping the rat SMA for 40 minutes, after which flow was restored and
      the SMA reperfused for 300 minutes. The blood levels of amylase and lipase were
      measured to reflect the dislocation of pancreatic juice. Organ injury parameters,
      such as the blood concentrations of alanine aminotransferase, creatinine kinase,
      and creatinine and the lung weight/body weight ratio were measured as well as
      inflammatory parameters such as tumor necrosis factor, hydroxyl radical, and
      nitric oxide levels. RESULTS: Organ injury and inflammatory parameters all
      increased significantly after I/R. Reperfusion of the intestine also induced a
      significant increase in the levels of pancreatic juice in the blood. After
      administration of the enzyme inhibitor, gabexate mesilate (FOY; 10 mg/kg), by
      injection into the duodenum, organ injury was significantly attenuated.
      CONCLUSIONS: These findings suggested that I/R of the SMA induced multiple organ
      injuries that appeared to be dependent on the translocation of pancreatic
      enzymes.

PMID- 17524834
TI  - Antioxidant vitamins preserve superoxide dismutase activities in gentamicin
      induced nephrotoxicity.
AB  - OBJECTIVE: The clinical use of gentamicin (G) is limited due to its known
      nephrotoxic actions. Generation of reactive oxygen species has been proposed as a
      causative factor of cell death in G-induced acute renal failure (ARF). Previous
      studies using superoxide dismutase (SOD) mimetics have indirectly suggested a
      role for the superoxide ion in G-induced ARF. In this study, we directly measured
      the enzyme activities using in situ isolated kidneys seeking to investigate the
      effects of antioxidant therapy on preservation of endogenous antioxidant levels
      in ARF. METHODS: Thirty-five male Sprague-Dawley rats were randomly assigned to 5
      groups: control, Tyrode-perfused; G, gentamicin (200 mg/L) added to the
      perfusate; G + vitamin E (Vit E; 100 mg/100 g BW, IM); G + vitamin C (Vit C)
      added to the drinking water for 3 days (200 mg/L) and to the perfusate (100
      mg/L); G + Vit E + Vit C. SOD activities were determined in renal tissues based
      on NAPDH oxidation at 340 nm by spectrophotometry. RESULTS: SOD activity was
      significantly reduced in the G group compared with the controls (P<.05).
      Administration of Vit E alone or in combination with Vit C significantly
      preserved enzyme activity levels compared with the G group (P<.05). CONCLUSION:
      Antioxidant vitamins have a role in preservation of renal endogenous antioxidant
      activities, namely SOD, in G-induced nephrotoxicity.

PMID- 17524835
TI  - Cyclosporine effects on the antioxidant capacity of rat renal tissues.
AB  - OBJECTIVE: Cyclosporine (CsA) has been shown to improve long-term survival after
      organ transplantation. However, CsA therapy is associated with a variety of side
      effects, among which nephropathy is the major one. Recent studies have suggested
      increased oxidative stress as a cause of drug nephrotoxicity. Therefore, this
      study was designed to evaluate the effects of CsA administration on the
      antioxidant capacity of kidney tissue. METHODS: Adult male Sprague-Dawley rats
      were randomly assigned into 2 groups: one group received CsA (25 mg/kg/d, IP for
      2 weeks) and a control group (no CsA administration). After 2 weeks, the kidneys
      of the rats from both groups were removed under anesthesia. A 50 mg fresh kidney
      tissue sample was homogenized in ice-cold phosphate buffer. Total antioxidant
      capacity (Ferric Reducing Ability of Plasma [FRAP]) in the homogenates was
      assayed based on the Benzie spectrophotometric method. RESULTS: FRAP in the
      kidney tissues had been significantly decreased by 2 weeks of CsA administration
      when compared with control rats (P<.05). CONCLUSIONS: These data suggested that
      CsA administration may decrease the antioxidant capacity of renal tissues. More
      studies on the evaluation of the protective effects of antioxidant therapy
      against CsA nephrotoxicity are underway.

PMID- 17524836
TI  - Kidney transplantation candidates and cardiovascular risk factors.
AB  - OBJECTIVE: We sought to determine the prevalence of cardiovascular disease and
      risk factors among chronic renal failure (CRF) patients on the transplantation
      waiting list. METHODS: Fifty CRF patients on chronic hemodialysis who underwent
      evaluation for transplantation were compared with 60 hypertensive patients
      matched for age. We used Framingham scoring to calculate the absolute risk;
      relative risk was calculated based on the low-risk Framingham cohort. RESULTS:
      According to traditional risk factors, a significant difference was observed in
      systolic blood pressure and total cholesterol (greater in the hypertensive
      group), and in the prevalence of the male gender, smoking, and diabetes, which
      were greater in the CRF group. The latter had a greater degree of left
      ventricular hypertrophy, lower diastolic blood pressure, and a lower prevalence
      of familial history of cardiovascular disease and obesity. Patients with CRF had
      a greater relative risk compared with the Framingham control population, but it
      did not differ from that observed in the group of hypertensive individuals.
      CONCLUSION: The prevalence of cardiovascular disease and traditional risk factors
      is high among renal transplantation candidates. The Framingham equations do not
      adequately quantify the real cardiovascular risk; other risk factors specific for
      that population probably contribute to their greater cardiovascular risk.

PMID- 17524837
TI  - Kidney disease in Bahrain: a biopsy-based epidemiological study.
AB  - The aim of this study was to establish the incidence of renal diseases in Bahrain
      during January 2003 through October 2006, based on biopsy results. This study
      continued a previous biopsy-based survey covering 13 years from January 1990
      through December 2002. Comparisons were made with the previous study to ascertain
      whether the disease pattern continued in the same trend. The current study
      included 145 biopsies on 130 patients, of whom glomerular diseases constituted
      64.8%; transplant biopsies, 23.4%; chronic glomerulosclerosis, 8.9%; and other
      etiologies, 4.1%. There were comparable numbers of primary and secondary
      glomerular diseases in the present series. The incidence of renal biopsies per
      100,000 population per year did not significantly change over the last 15 years:
      5.4/100,000 per year in the present series versus 5.8/100,000 per year in the
      previous study. The pattern of primary glomerular diseases showed the minimal
      change disease--focal segmental glomerulosclerosis (MCD-FSGS) complex--remained
      the most common of all primary glomerular diseases, although decreased in
      absolute numbers compared with the previous study. A significant increase in the
      number of patients with immunoglobulin A nephropathy was observed over the years.
      Secondary glomerular diseases showed an increased incidence with lupus nephritis
      the number one diagnosis. Also we observed a steady increase in the number of
      allograft biopsies.

PMID- 17524838
TI  - Factors associated with peak oxygen uptake in hemodialysis patients awaiting
      renal transplantation.
AB  - The preoperative evaluation of pulmonary function is important in renal
      transplantation candidates. Exercise capacity determined by peak oxygen uptake
      (peak Vo(2)) is a predictor of perioperative mortality and survival. The aim of
      this study was to determine the factors associated with the peak Vo(2) among
      renal transplantation candidates undergoing hemodialysis. Thirty patients with
      chronic renal failure including 14 women and 16 men of mean age 40.2 +/- 10.3
      years had a mean duration of dialysis of 133.1 +/- 63.3 months and were awaiting
      renal transplantation. None of the patients had signs or symptoms of active
      infection or inflammation. Each patient underwent pulmonary function and symptom
      limited cardiopulmonary exercise tests. Despite the absence of clinically evident
      inflammation, a malnutrition inflammation score was calculated for each patient
      to assess comorbid conditions and the risk of atherosclerosis. Demographic and
      laboratory parameters were obtained from hospital records. The peak Vo(2) was
      positively correlated with the serum triglyceride level and negatively correlated
      with serum ferritin level and malnutrition inflammation score. On multiple linear
      regression analyses, which were performed to assess the potential predictors of
      the peak Vo(2), the malnutrition inflammation score was the only variable that
      independently correlated with the peak Vo(2) in hemodialysis patients awaiting
      renal transplantation. In conclusion, peak Vo(2) is associated with markers of
      nutrition and the malnutrition inflammation score. We suggest that chronic
      malnutrition and silent inflammation may be responsible for the preoperative
      decreased exercise capacity in renal transplantation candidates undergoing
      hemodialysis.

PMID- 17524839
TI  - Value of the tuberculin skin test in screening for tuberculosis in dialysis
      patients.
AB  - BACKGROUND: Hemodialysis patients are at high risk for tuberculosis, and a
      tuberculin skin test (TST) is not usually helpful in detecting tuberculosis
      infection because of anergic reactions. Prophylactic therapy against tuberculosis
      in dialysis patients is important to enhance transplantation success. Herein we
      evaluated the value of TST in screening for tuberculosis and analyzed any
      compounding factors that might affect the results of the test in hemodialysis
      patients in an endemic area of Turkey. METHODS: A total of 187 (96 female, 91
      male) patients were screened using a 2-step TST. Test results were compared with
      clinical, radiologic, and laboratory data. RESULTS: None of the patients had
      active tuberculosis during the study and 55% had been vaccinated against
      tuberculosis. After the first purified protein derivative (PPD) test, 55.1% of
      the patients showed a positive reaction, ultimately reaching a total of 68.4%
      following the second test. Cumulative positive TST results were significantly
      correlated with male gender (P=.001, r=.352), previous tuberculosis history
      (P=.013, r=.183) positively, whereas with the ferritin level (P=.001, r=-.233)
      negatively; but there were no significant relationships between TST results and
      other data. CONCLUSIONS: Impairment of delayed-type hypersensitivity reaction is
      frequent in dialysis patients, but we observed high rates of positivity with the
      two-step TST which could be attributed to tuberculosis being endemic in Turkey.
      Further comparative studies with more specific diagnostic methods will be helpful
      to evaluate the importance of TST positivity in identifying tuberculosis-infected
      HD patients.

PMID- 17524840
TI  - Are large nonfunctional kidneys risk factors for posttransplantation urinary
      tract infection in patients with end-stage renal disease due to autosomal
      dominant polycystic kidney disease?
AB  - OBJECTIVES: The objective of this study was to evaluate the effect of bilateral
      nephrectomy on posttransplantation urinary tract infection (UTI) among patients
      with end-stage renal disease (ESRD) due to autosomal dominant polycystic kidney
      disease (ADPKD). METHODS: In a retrospective case-control design, 62 patients
      with ESRD with ADPKD were divided into 2 groups: (A) 24 patients who underwent
      bilateral nephrectomies, and (B) 38 patients in whom bilateral nephrectomies had
      not been done. Pretransplantation and posttransplantation urine cultures were
      evaluated for UTI. RESULTS: Sixty-two patients with ESRD with ADPKD were enrolled
      in this study. The average age was 42 years (range, 6-60 years). Forty patients
      (64.5%) were male and 22 (35.5%) were female. The mean duration of hemodialysis
      was 24 months (range, 2-120 months), which was the same for both groups.
      Bilateral nephrectomies were done for 24 participants (38.7%). There were 38
      patients (61.3%) in group B who did not have the operation. UTI occurred in 23
      patients (37.1%): 6 patients (25%) in group A and 17 patients (44.7%) in group B.
      The incidence of UTI was not statistically different between the 2 groups
      (P>.05). Furthermore, no relationship was found between age, gender, blood group,
      and UTI in patients with ADPKD (P>.05). CONCLUSION: According to our study, the
      presence of large nonfunctional kidneys is not a risk factor for
      posttransplantation UTI in patients with ADPKD and ESRD.

PMID- 17524841
TI  - Pleural effusion in long-term hemodialysis patients.
AB  - As a consequence of the expanded use of long-term hemodialysis and extended life
      spans, complications of chronic renal failure are encountered with an increased
      frequency among uremic patients. Such patients may develop many thoracic and
      extrathoracic problems--most frequently uremic pleuritis and pericarditis, uremic
      pneumonia, infection, and metastatic pulmonary calcification. We retrospectively
      analyzed the medical records of 257 patients who had received long-term
      hemodialysis between 1990 and 2006 to better understand the incidence, causes,
      and clinical features of pleural effusions in this population. The incidence of
      pleural effusion in hospitalized patients receiving long-term hemodialysis was
      20.2% (n=52; mean age, 55.83 +/- 16.56 years; male-to-female ratio, approximately
      3:2). Pleural effusion resulted from hypervolemia in 61.5% and was bilateral in
      68.8% of patients. Unilateral effusion was present in 25 of 52 (48%) patients.
      The most frequent causes of unilateral effusion were hypervolemia (n=9) and
      parapneumonic effusion (n=5). Thoracenteses were performed in 14 of the 52
      patients in the study group. Of thoracenteses performed, 64.3% of the patients
      had transudative pleural effusion and 35.7% had exudative effusion. Transudative
      pleural effusion resulted from hypervolemia in 66.7% and heart failure in 22.2%.
      Of the patients with transudative effusion, 85.7% were bilateral. The most
      frequent cause of exudative pleural effusion was uremic pleuritis, which occurred
      in 40% of the patients. The most common symptom was dyspnea, which occurred in
      53.8% of patients. In conclusion, pleural effusions are common in patients
      receiving chronic hemodialysis. Thoracentesis may be performed in patients with
      unilateral pleural effusion. Since hypervolemia was the most common cause of
      pleural effusion, this complication should not be considered an obstacle in renal
      transplant recipients.

PMID- 17524842
TI  - Study of the effect of renal transplantation on methacholine challenge test in
      patients with end-stage renal failure in Shahid Doctor Labafinejad Hospital in
      Tehran, Iran.
AB  - Pulmonary complications are common in patients with chronic renal failure (CRF).
      The objective of this study was determine the effect of renal transplantation on
      pulmonary function, using a methacholine challenge test. This interventional
      study included 14 CRF patients on maintenance dialysis who underwent serial
      spirometry and astography before and after renal transplantation. None of them
      was known to have clinically important pulmonary or heart disease. The results of
      spirometry, astography, echocardiography, and chest X-ray were normal. Five
      patients were men and all others were women. The overall age range was 15 to 45
      years (mean age = 28.6 +/- 10.9). For every patient four times astography was
      done. The mean values of spirometric and astography indices before and after
      renal transplantation were within normal limit. But by repeated measure analysis
      of variance, the results actually showed improved airway responsiveness (although
      within normal limits). The most common pathological lung condition in CRF is
      pulmonary edema, usually due to a combination of fluid overload and abnormal
      permeability of the pulmonary microcirculation. However, our patients had no
      symptomatic pulmonary edema, but minor degrees of fluid retention are virtually
      impossible to detect clinically and could not be excluded. Therefore, it seems
      that disappearance of subclinical pulmonary edema was the likeliest cause of an
      increase in minimum dose of methacholine, and therefore improvement in airway
      responsiveness after renal transplantation.

PMID- 17524843
TI  - Kidney transplantation: is there any place for refugees?
AB  - There are more than 8 million refugees worldwide with the Middle East bearing the
      brunt. Socioeconomic factors are the major obstacles that refugees encounter when
      seeking health care in the host country. It, therefore, comes as no surprise that
      refugees are denied equal opportunities for one of the most sophisticated and
      expensive medical procedures in the world, kidney transplantation. With respect
      to transplantation, refugees are caught between a rock and a hard place: as
      recipients they have to single-handedly clear many hurdles on the arduous road to
      renal transplantation and as donors they are left unprotected against human organ
      trafficking. It should be the moral responsibility of the host country to provide
      this population with a support network. The ways and means of establishing this
      network should be defined locally; nevertheless, enabling refugees to receive a
      transplant is the most basic step, which should be followed by the provision of
      financial support and follow-up facilities in a concerted effort to ensure the
      continued function of the invaluable graft. It is also necessary that refugees be
      protected from being an organ reservoir on the black market. There are no precise
      regional or international data available on kidney transplantation in refugees;
      among the Middle East Society for Organ Transplantation countries, only Iran,
      Saudi Arabia, Pakistan, and Turkey have thus far provided data on their
      respective kidney transplantation regulations and models. Other countries in the
      region should follow suit and design models tailored to the local needs and
      conditions. What could, indubitably, be of enormous benefit in the long term is
      the establishment of an international committee on transplantation in refugees.

PMID- 17524844
TI  - Results of kidney transplantation between spouses: a single-center experience.
AB  - The shortage of cadaveric kidneys is growing in Turkey despite intensive efforts
      to find a solution. Living related donors are the primary source of kidneys in
      developing countries. When a first-degree relative of the patient is not
      available, a second-degree relative or a genetically unrelated but emotionally
      related donor, such as a spouse, becomes an alternative. From November 1985 to
      June 2006, 81 living unrelated kidney transplantations were performed between
      spouses at our hospital. Seventy-one of the donors were women, and 10 were men.
      The mean donor age was 33.9 +/- 8.5 years and the mean patient age was 38.5 +/-
      8.8 years. The posttransplantation patient and graft survival rates were. 1 year:
      93% patient survival, 83% graft survival; 3 years: 90% patient survival, 78%
      graft survival; and 5 years: 83% patient survival, 76% graft survival. During the
      posttransplantation period (mean, 82.5 +/- 61.4 months range, 6-216 months),
      seven patients died: three from sepsis, one from gastrointestinal hemorrhage, two
      from myocardial infarction, and one from pancreatitis. Three of those seven
      patients died with a functioning graft, and the seven other grafts were lost
      because of chronic rejection. To obstruct the underground trade in organs sold
      for transplantation, our center does not accept living unrelated organ donor
      candidates other than a spouse. Interspousal kidney transplantation is an
      important option with good clinical results. It provides the couple with a better
      quality of life, offers the opportunity to share the joy of giving, and enables a
      husband and wife to receive the "gift of life" from each other.

PMID- 17524845
TI  - Which primary diagnosis has the highest in-hospital mortality rate for kidney
      recipients?
AB  - OBJECTIVES: Although "in-hospital mortality" for several post-renal
      transplantation complications has been reported in various studies, there is no
      single published single-center study that compares their hospital mortality
      rates. We sought to rank the primary diagnoses post-renal transplantation by
      means of in-hospital mortality. METHODS: We selected 404 consecutive
      rehospitalizations following kidney transplantation from 2003 to 2005. The causes
      of rehospitalization were categorized into infection, allograft rejection,
      surgical complication, cerebrovascular accidents (CVA), malignancy, medication
      complications, and miscellaneous. Fatality was defined as the relative frequency
      of death due to the same cause among all admissions. RESULTS: The mortality rate
      (MR) was 5.7%. From the 23 cases of death, 17 (74%) had a functioning kidney at
      the time of death. The MR was 40% for CVA, 14.3% for surgical complications,
      11.1% for miscellaneous, 5.3% for drug complications, 7% for infections, and 4.8%
      for graft rejection (P=.002). No death was observed among cases with a diagnosis
      of malignancy or nephrolithiasis. Inpatient mortality was higher among those with
      more than one diagnosis at admission: 42.9% for more than two diagnosis, 7.1% for
      those with two diagnosis, and 4.2% for those with one diagnosis (P=.001).
      CONCLUSIONS: The in-patient mortality ranking is totally different from the
      ranking of causes of death in renal recipients. In other words, infection is the
      leading cause of death due to high incidence, and not high fatality. More rare
      complications, including CVA and surgical complications, are more often fatal.

PMID- 17524846
TI  - Cadaveric kidney transplantation: five years experience at a single center.
AB  - BACKGROUND: In the past, the majority of renal transplantations in Iran were from
      living donors, but recently cadaveric donation of organs is increasing. We
      reviewed our experience on kidney transplantation from cadaveric donors for the
      past 5 years in our center. METHODS: Between July 1998 and September 2004, 122
      kidneys were removed from 61 cases of brain-dead patients and transplanted in 114
      patients with end-stage renal disease in our center. Two kidneys had tumoral
      involvement and were discarded. Three kidneys were transplanted in other centers
      and three patients received en bloc kidney transplantations. In addition, we
      performed nine cases of heart, one case of liver, and one case of lung
      transplantations. All the recipients were followed for at least 1 year and
      posttreatment renal function and graft survival were determined. RESULTS: All
      cadaveric donors were brain dead due to car (30%) and motocycle (70%) accidents,
      with ages ranging from 5 to 56 years (mean, 24/4 years). The mean warm and total
      cold ischemia times were 7 minutes and 8.1 hours, respectively. The mean distance
      between harvesting center and our hospital was 65 km. The 1-year graft survival
      was 92.3%, with mean serum creatinine of 1.76 +/- 0.79 at 1 year. Of other
      transplanted organs, the liver and lung recipients died 24 hours and 45 days
      after operation. Among heart recipients, four are still alive. CONCLUSION:
      Cadaveric donors in developing countries including Iran can be excellent sources
      of organ donation.

PMID- 17524847
TI  - Iranian model of renal allograft transplantation in 3028 recipients: survival and
      risk factors.
AB  - BACKGROUND: Considering the organ shortage crisis for renal transplantation
      worldwide, assessing the risk factors to establish better allocation strategies
      to improve graft survival seems to be crucial. OBJECTIVES: We aimed to evaluate
      the risk factors influencing graft and patient survival after renal
      transplantation to construct a model of prognostic factors for living renal
      transplantation (LRT), namely living unrelated renal transplantation (LURT).
      METHODS: We designed a retrospective multicenter survey including medical record
      review of 3028 patients who received renal transplants at 2 hospitals between
      July 1984 and December 2005. We assessed the impact on graft survival of
      recipient/donor relationship, recipient age and gender, donor age and gender, and
      viral hepatitis B and C infections. RESULTS: Among 3028 recipients, including
      94.8% primary grafts, 63.4% were men, mean +/- SE of age 36.4 +/- 0.3 years, with
      mostly end-stage renal disease due to diabetes mellitus, hypertension, or
      glomerulonephritis. One-, 5-, 10- and 15-year graft survival rates were 85.4%,
      68.3%, 46.4%, and 23.8%, respectively. Patient survival rates were 93.4%, 87.5%,
      79.4%, and 66.4% at the above intervals, respectively. Donor age (relative hazard
      [RH], 1.024; P<.001), unrelated donors (RH, 1.7; P<.001), and hepatitis C virus
      (HCV) infection (RH, 2.65; P<.001) were the only significant factors affecting
      graft survival. CONCLUSION: Increased donor age, unrelated donor, and HCV
      infection were significant factors negatively impacting graft survival; thus,
      proper management of these factors may lead to better graft and patient survival.

PMID- 17524848
TI  - Renal transplantation in children.
AB  - OBJECTIVE: Renal transplantation is the preferred method for the treatment of
      children in end-stage renal disease (ESRD). In this retrospective study, we
      analyzed the results at our center. PATIENTS AND METHODS: Between November 1993
      and June 2006, 86 children (50 boys and 36 girls) received organs from 50 living
      donors (LDTx) and 36 cadaveric donors (CDTx). Twenty children were <10 years. In
      addition to ESRD, some patients had one or more other high-risk factors, eg,
      abnormal lower urinary tract in 36 recipients (42%). The procedure was a
      preemptive transplantation in 28, and a retransplantation in 9 recipients.
      Induction immunosuppression used either antithymocyte globulin (43 cases) or anti
      interleukin-2 receptor antibodies (20 cases). RESULTS: Patients were followed for
      6 to 150 months. There were 24 surgical complications (28%), 26 acute rejection
      episodes (33%), and 17 of systemic bacterial or viral infections. Two recipients
      died at 1 and 21 months. The 14 grafts were lost at 1 day to 87 months. The 1-
      and 10-year actuarial survival rates were 99% and 98%, respectively, for the
      recipients, and 88% and 84%, respectively, for the grafts. The 10-year actuarial
      graft survival rates were 98% in LDTx and 64% in CDTx; 86% in recipients >10
      years old and 75% in recipients <10 years old. Abnormal urinary tract,
      pretransplantation dialysis, and transplant number showed no effect on graft
      survival. All pediatric recipients with functioning grafts are fully
      rehabilitated. CONCLUSION: Renal transplantation is the preferred method of
      treatment for children in ESRD. Higher graft survival rates were achieved in
      older children and following LDTx.

PMID- 17524849
TI  - Does donor nephron mass have any impact on graft survival?
AB  - OBJECTIVES: Functioning nephron mass namely, the number of nephrons in the
      grafted kidney, is one of the nonimmunologic factors that may have some impact on
      long-term graft survival. The aim of this study was to assess the impact of donor
      nephron mass on graft outcome in the recipient. MATERIALS AND METHODS: From 1989
      to 2005, 1000 renal transplants were performed at our center. The 217 studied
      cases were followed for an average of 8 years. All patients received grafts from
      living donors. The weight of the grafted kidney (donor nephron mass) as well as
      the recipient's body mass index (BMI) were measured at the time of operation.
      Nephron mass index (NMI) was defined as the ratio of donor nephron mass to
      recipient BMI. Associations between variables were tested by logistic regression
      and Pearson correlation using the SAS system and S-plus statistical software. To
      evaluate graft function, we determined serum creatinine values, acute rejection
      episodes and chronic nephropathy. RESULTS: Mean NMI was 8.07 +/- 0.2 and mean
      creatinine level was 1.43 +/- 0.4 mg/dL. There were 32 cases (14.7%) of acute
      rejection, who were managed successfully with antithymocyte globulin (ATG) in 28
      cases. Four patients lost their grafts. There were 15 cases (7%) of graft loss
      due to chronic rejection. Using Pearson correlation, we observed no association
      between NMI and mean serum creatinine level. Logistic regression showed a
      significant relation between NMI and acute rejection (P<.05) with an odds ratio
      of 2.0. There was no significant correlation between NMI and chronic rejection.
      CONCLUSIONS: The lower the NMI, the greater the short-term graft loss. However,
      in the long term, no significant correlation was found between graft survival and
      NMI. Also, mean creatinine level was not significantly different among patients
      regardless of NMI.

PMID- 17524850
TI  - A logistic regression model for predicting health-related quality of life in
      kidney transplant recipients.
AB  - BACKGROUND: To develop a logistic regression model capable of predicting health
      related quality of life (HRQOL) among kidney transplant recipients and determine
      its accuracy. METHODS: Three groups of patients were selected: 70 healthy
      controls, 136 kidney transplant patients as a derivation set, and another 110
      kidney transplant patients as a validation set. SF-36 score was used for HRQOL
      measurement. A cutoff point to define poor versus good HRQOL was calculated using
      the SF-36 scores of healthy controls. A logistic regression model was used to
      derive predictive parameters from the derivation set. The derived model was then
      tested among the validation set. HRQOL predictions made by the model for the
      patients in the validation set and the SF-36 scores were compared. We calculated
      sensitivity, specificity, positive and negative predictive values, and model
      accuracy. RESULTS: SF-36 scores below 58.8 were defined as an indication of poor
      HRQOL. The regression model suggested that poor HRQOL was positively associated
      with lower education (below high school diploma), being single or widowed, and
      diabetes/hypertension as etiology. It was negatively associated with younger age
      (<45 years) at the time of transplantation. Optimal sensitivity and specificity
      were achieved at a cutoff value of 0.74 for the estimated probability of poor
      HRQOL. Sensitivity, specificity, positive and negative predictive values, and
      accuracy of the model were 73%, 70%, 80%, 60%, and 72%, respectively. CONCLUSION:
      The suggested model can be used to predict poor posttransplant HRQOL among renal
      graft recipients using simple variables with acceptable accuracy. This modal can
      be of use in decision making in the recipients for whom achieving good HRQOL is
      the main aim of transplantation, to select high-risk patients and to start
      interventional programs to prevent a poor HRQOL.

PMID- 17524851
TI  - Renal transplantation in Iran over the past two decades: a trend analysis.
AB  - BACKGROUND: In this study, we have reported updated statistics of the Iranian
      Transplantation Registry, the status of the recipients and grafts, and a detailed
      time trend with respect to patient characteristics. METHODS: We retrospectively
      reviewed the Iranian Renal Transplantation Registry and information from the
      Dialysis and Transplant Patients Public Association, to obtain data on all kidney
      transplantations performed in Iran between 1986 and 2005. Data were gathered
      regarding the total number of transplantations, graft loss, recipient death, and
      donor and recipient characteristics, including demographic data, cause of end
      stage renal disease (ESRD), and source of kidney. We assessed changes in
      variables on a biannual basis. RESULTS: A total of 19521 transplantations were
      registered over the study period, of which, 761 recipients (3.9%) had died and
      2333 allografts (11.9%) had been lost. The source of the kidney in 2556 (13%)
      subjects was a living related donor (LRD), in 16234 (83%) a living unrelated
      donor (LURD), and in 831 (4%) cadaveric. During the study decades we noted an
      increase in the number of kidney transplantations (from 22 to 3690), age of
      recipients (from 30 to 40), male-to-female ratio of recipients (from 0.58 to
      0.67), male-to-female ratio of donors (from 0.48 to 0.52), diabetes mellitus
      (from 0% to 27%), and hypertension (from 4% to 15%), as causes of ESRD, as well
      as the use of cadaveric kidneys (0% to 11%). CONCLUSION: Analyzing renal
      transplantation data not only helps to evaluate the effectiveness of
      transplantation activities in a country, but also provides information to
      estimate future costs in the health care system.

PMID- 17524852
TI  - The cost of kidney transplantation in Iran.
AB  - BACKGROUND: Kidney transplantation has gained widespread popularity by improving
      the outcome of end-stage renal disease (ESRD) patients. However, this is a highly
      complicated and expensive procedure that puts much pressure on the health system
      in developing countries. We report the costs in Iran model of kidney
      transplantation. MATERIALS AND METHODS: We reviewed the regulations for kidney
      transplantation using Dialysis and Transplant Patients Association (DATPA)
      information, 2005. All data regarding the cost of transplantation procedure,
      immunosuppression, and the money given to donors were included. The cost of
      transplantation procedure was categorized into personnel, drugs, paraclinics,
      hospital bed, and other expenses. To achieve more comprehensive results, all
      costs were converted into US dollars (1 USD = 9000 Rials). RESULTS: The total
      cost of kidney transplantation procedure was $9224. Of this, 65.8% ($6076) was
      related to the immunosuppression therapy in the first year, 22.2% ($2048) to the
      transplantation procedure, and 12% ($1100) to organ procurement. The details of
      donor nephrectomy were as follows: personnel, $183; accommodations, $107; drugs,
      $39; paraclinics, $23; and other, $22. These values for kidney recipient were
      personnel, $331; drugs, $367; paraclinics, $278; accommodations, $475; and other,
      $222. CONCLUSION: Compared with other countries, the kidney transplantation cost
      is low in Iran. The health system also pays for all the expenses. These, along
      with full medical insurance coverage of kidney recipients, make kidney
      transplantation available for every patient, regardless of the socioeconomic
      status due to its low cost. It is expected that a higher number of
      transplantation candidates with a low socioeconomic status will select
      transplantation.

PMID- 17524853
TI  - Data-entropy analysis of renal transplantation data.
AB  - INTRODUCTION: The terms entropy and robustness are currently used by biomedical
      investigators to predict the risk of change in a system. The former is the
      mathematical identification of uncertainty about a system, while the latter is
      the likelihood of system stability. We conducted an entropy-based analysis of our
      renal transplantation data set. MATERIALS AND METHODS: The input variables in our
      model included donors and recipients, past medical history, and other clinical
      data. The output variables were 6- month, 1-year, and 2- year patient and graft
      survivals. Data-entropy analysis was performed with Ontonix s.r.l. software
      (www.ontonix.com). RESULTS: The total input and output entropy was 13.14 and
      1.54, respectively. The mean input and output robustness was 39.14% and 29.54%.
      The robustness amplification index was 0.75. The minimum entropy of the input
      variables was reported for a history of myocardial infarction (0.07), vascular
      disease (0.1), bladder residual (0.13), or urologic surgery (0.15). The minimum
      entropy of the output variables was 0.20 for 6-month patient survival; 0.22 for 1
      year patient survival; 0.25 for 6-month graft survival; 0.27 for 1-year graft
      survival; 0.28 for 2-year patient survival; and 0.32 for 2-year graft survival.
      CONCLUSION: Data-entropy analysis demonstrated a high stability of our
      transplantation data set. Nevertheless, long-term outcomes, especially those of
      graft survival, were slightly more unpredictable.

PMID- 17524854
TI  - Time-dependent variations in urine output after renal transplantation.
AB  - INTRODUCTION: Diuresis begins soon after renal transplantation. Although
      controversial, early post kidney transplant urine volume may correlate with
      favorable short- and long-term allograft survival. The aim of the present study
      was to examine the potential changes in urine volume within the first 6 months
      after renal transplantation. METHODS: In a prospective study, the first month
      serum creatinine level and daily urine volume were measured at 24 and 48 hours,
      and at 1 month after renal transplantation in patients with stable kidney
      function without the evidence of allograft rejection (n = 54). Fifteen patients
      were also followed for their urine output at least 6 months post kidney
      transplantation. Data are expressed in mean values +/- SD. Statistical analysis
      was performed by SPSS version 13.0 using ANOVA. Correlation between continuous
      variables was performed using the Pearson test. The P value was set at .05.
      RESULTS: The mean age of the renal allograft recipients was 35.5 +/- 12.1 years
      with a male to female ratio of approximately 1.3. The mean first month serum
      creatinine was 1.26 +/- 0.4 mg/dL. The mean urine outputs were 10.06 +/- 5.89,
      5.45 +/- 3.05, and 3.44 +/- 1.25 L at 24 and 48 hours and 1 month post renal
      transplantation. Those patients who were followed for 6 months post transplant
      (n=15) were observed to have a mean urine volume of 3.20 +/- 1.24 L at the end of
      this period. This trend showed that urine volume steadily decreased from 24 and
      48 hours to 1 month after renal transplantation (P<.05). However, urine volumes
      were rather comparable at one month and 6 months after transplantation (P>.05). A
      positive correlation was found between the first-month serum creatinine and the
      urine volume at one month (r=0.302 and P=.035). CONCLUSION: Although urine volume
      showed considerable variation early after renal transplantation, it stabilized by
      1 month after transplantation, which was also positively correlated with the
      first-month serum creatinine. Moreover, we concluded that in stable patients, the
      final urine output was related to early graft function.

PMID- 17524855
TI  - Serum C-reactive protein surge in renal transplant recipients: link with
      allograft survival.
AB  - The restoration of kidney function by transplantation improves the common finding
      of chronic inflammation in patients with end-stage renal disease (ESRD). The C
      reactive protein (CRP) level is a reliable marker of inflammation in renal
      transplant recipients. We analyzed the predictive value of posttransplant CRP
      surges on renal allograft survival among 141 ESRD patients who underwent renal
      transplantation between May 1999 and September 2001 at our institution. Twenty
      seven cadaveric and 114 living donors were also studied. The subjects'
      demographic, clinical, and laboratory data were recorded. The renal transplant
      recipients were divided into three groups defined by the type of serum CRP surge:
      a normal, intermittently high, or consistently high serum CRP concentration.
      Renal allograft survival rates were 90.0% among recipients with normal serum CRP
      concentrations, 72.6% among those with intermittently high concentrations, and
      11.1% in those with consistently high concentrations. A Cox regression analysis
      of factors that affect allograft survival showed that acute rejection, advanced
      recipient age, and consistently high serum CRP concentrations were associated
      with a high risk of renal allograft loss. Intermittent elevations in the serum
      CRP level were not associated with an increased risk of allograft loss, according
      to the Cox regression model. We concluded that consistently high serum CRP
      concentrations in renal allograft recipients showed a high negative predictive
      value for renal allograft survival. In recipients who exhibited ongoing
      inflammatory process in the 5-year posttransplant period, additional efforts are
      necessary to manage inflammation and therefore prolong renal allograft survival.

PMID- 17524856
TI  - Early onset proteinuria after renal transplantation: a marker for allograft
      dysfunction.
AB  - The objective of this study was to determine whether early proteinuria after
      renal transplantation affected long-term allograft survival. The 130 patients
      included 105 men and 25 women of overall mean age, 29.6 +/- 9.6 years. There were
      105 living related and, 25 cadaveric donor transplants. Proteinuria was defined
      as a level in of more than 300 mg/d. Donor and recipient age at transplantation,
      duration of pretransplant dialysis, donor type (living related or cadaveric), the
      presence of delayed graft function or acute rejection, panel-reactive antibodies,
      the number of human leukocyte antigen mismatches, and the systolic blood pressure
      level were retrospectively recorded for the study subjects. Cox regression
      analysis was used to determine the effects of proteinuria on allograft survival.
      Patients with proteinuria demonstrated significantly lower graft survival rates
      than did those without proteinuria (54.17% vs 82.62%, respectively; P<.002).
      Proteinuria at the third month after transplantation (P<.004, odds ratio
      [OR]=3.26, confidence interval [CI]=1.46 to 7.29), donor age (P<.001, OR=1.06,
      CI=1.02 to 109), and panel-reactive antibodies (P<.041, OR=1.06, CI=1.00 to 1.12)
      were significantly associated with decreased allograft survival. Early
      proteinuria after renal transplantation was indicative of a high risk for
      allograft dysfunction. A reduction of proteinuria may be associated with improved
      graft survival.

PMID- 17524857
TI  - Effect of hypertension on transplant kidney function: three year of follow-up.
AB  - BACKGROUND: Hypertension significantly increases the risk for chronic graft loss
      and accelerates the deterioration of transplanted kidney function. Aggressive
      control of blood pressure (BP) is recommended in the posttransplant period when
      maintenance levels of immunosuppressive drugs are achieved. The aim of this study
      was to investigate whether the improved control improved the graft survival.
      METHODS: We compared transplant kidney function in two groups of hypertensive
      patients matched for age, gender, donor-recipient relation, primary disease,
      early posttransplant course, and immunosuppressant and hypertensive therapy
      during 3 years follow-up. The patients were divided into satisfactory and
      unsatisfactory controlled blood pressure. Group 1 consisted of 98 patients with
      satisfactory BP control (arterial pressure <160/90 mmHg) and group 2, 98 patients
      with unsatisfactory BP control. RESULTS: The mean through levels of cyclosporine
      in whole blood were similar in both groups and did not exceed 185 ng/mL. A slow
      but significant increase in mean creatinine levels was observed among group 2
      during 3 years follow-up, whereas, among group 1, graft function remained stable.
      Cardiovascular events were observed only in group 2: stroke in one patient and
      death because of heart failure in one patient. Factors which correlated with
      development of post transplant hypertension were age, gender, duration of disease
      before transplant, and underlying disease. CONCLUSION: Lowering BP, even several
      years posttransplantation, was associated with improved graft and patient
      survival in renal transplant recipients.

PMID- 17524858
TI  - Histopathologic evaluation of pretransplant biopsy as a factor influencing graft
      function after kidney transplantation: a 1-year observation.
AB  - INTRODUCTION: Many factors affect long-term results in kidney transplantation
      including histologic damage as a independent predictor, such as chronic
      allograft/nephropathy in protocol biopsies and age-dependent lesions.
      Histopathologic findings correlate with the incidence of delayed graft function,
      renal function, and allograft survival, allowing a rather precise prediction of
      graft outcome. MATERIALS AND METHODS: We analyzed 92 renal thick needle
      preimplantation and 29 postexplantation biopsies. Biopsies were preserved in 4%
      formalin and immersed in paraffin. Optimal biopsies contained at least 10
      glomeruli and at least 2 cross-sections of arteries. We analyzed tubulitis,
      intensity of acute tubular necrosis, inflammatory infiltration,
      glomerulonephritis, arterial hyalinization, arteritis, fibrosis, tubular atrophy,
      arterial intimal fibrosis, increase of mesangial matrix, and percentage of
      glomerulosclerosis. During the postoperative course we analyzed patients
      condition, exigency of postoperative dialysis, urine output, as well as serum
      concentrations of creatinine, urea, uric acid, and ions. During a 1-year
      observation period, we analyzed living recipients, graft loss, death with a
      functioning graft, incidence of nephropathy (CAN), and acute rejection episodes
      (ARE). RESULTS: We observed a significant correlation between immediate graft
      function (IGF) and lack of ATN in the pre-0 biopsy. We observed no correlation
      between renal function and arterial hyalinization and fibrosis, inflammatory
      infiltration, tubular atrophy. In the postoperative period, we observed a
      significant correlation between IGF and lack of interstitial fibrosis with
      significantly lower levels of creatinine, urea, and potassium and higher urine
      output early after transplantation. IGF and better function of the right kidney
      was correlated with shorter time to reach a creatinine level of 2 mg%. In the
      postoperative periods, we also observed a difference between renal function
      depending on gender. The presence of acute tubular necrosis, arterial fibrosis,
      lack of inflammatory infiltration in the pre-0 biopsy correlated with worse late
      renal function. Among explantation biopsies 65.5% showed signs of CAN, and
      37.93%, histologic marks of ARE.

PMID- 17524859
TI  - Microchimerism and renal transplantation: doubt still persists.
AB  - OBJECTIVE: We sought to study microchimerism in a group of kidney transplant
      recipients. MATERIALS AND METHODS: In this study, the peripheral blood
      microchimerism (PBM) after renal transplantation was retrospectively evaluated in
      32 male-to-female recipients of living unrelated or cadaveric donor renal
      transplants. Using a nested polymerase chain reaction (PCR) amplification
      specific for SRY region of the Y chromosome, microchimerism was detected with a
      sensitivity of 1:1,000,000. Recipients were compared according to the presence of
      PBM, acute and chronic rejection episodes, type of allotransplant, recipient and
      donor age at transplantation, previous male labor or blood transfusion, allograft
      function (serum creatinine level), and body mass index. RESULTS: Among 32
      recipients, 7 (21.9%) were positive for PBM upon multiple testing at various
      posttransplant times. All microchimeric recipients had received kidneys from
      living unrelated donors. No significant difference was observed with regard to
      other parameters. In addition the acute rejection rate in the microchimeric group
      was 3 (42%) versus 4 (16%) in the nonmicrochimeric recipients (not significant).
      CONCLUSION: Our results suggested better establishment of microchimerism after
      living donor kidney transplantation. However, doubt persists concerning the true
      effect of microchimerism after renal transplantation. It seems that
      microchimerism alone has no major protective role upon renal allograft survival.

PMID- 17524860
TI  - Calcitriol started in the donor, expands the population of CD4+CD25+ T cells in
      renal transplant recipients.
AB  - OBJECTIVES: Alloreactive T cells recognize antigens via direct and indirect
      pathways. The competency of costimulatory molecules on antigen-presenting cells
      (APC) is important. An active form of vitamin D (1,25(OH)(2)D(3), calcitriol)
      inhibits APC cell maturation and expression of costimulatory molecules. Herein we
      studied the immunosuppressive effects of calcitriol, which was started in the
      donors and continued in the kidney recipients. METHODS: In this prospective
      study, candidates for living donor renal transplantation were randomly assigned
      into two groups: the treatment group were prescribed calcitriol (0.5 microg/day)
      started in the donor 6 days before donation and continued in recipient side for 6
      months after transplantation. The control group received the conventional
      immunosuppressive regimen, namely, cyclosporine/mycophenolate mofetil and
      prednisolone. In each group, a recipient blood sample was obtained before and 6
      months after transplantation. Diagnostic study of the T-cell markers-CD3, CD4,
      and CD25-were performed with a flow cytometry technique. RESULTS: The mean values
      of CD3(+)CD4(+)CD25(+) T cells in the treatment group (four women and five men;
      40.8 +/- 8.5 years) and the control group (four women and six men; 37.2 +/- 10
      years) were at 14.2 +/- 4.2% and 15.4 +/- 4.5% of total peripheral lymphocytes.
      Six months after transplantation, these percentages increased to 29 +/- 6.3% in
      the treatment group and decreased to 12.1 +/- 4.5% in the controls (P<.0001). No
      clinical rejection was detected in either group during the study period.
      CONCLUSION: Calcitriol started in the donors and continued in the kidney
      allograft recipients lead to expansion of CD4(+)CD25(+) regulatory T cells in
      recipients. We speculated that costimulatory deficient APC for both direct and in
      direct pathways may play a role.

PMID- 17524861
TI  - Genetic association of interleukin-4, interleukin-10, and transforming growth
      factor-beta gene polymorphism with allograft function in renal transplant
      patients.
AB  - Despite advances in immunosuppressive therapy in the past decade, allograft
      rejection remains the primary cause for kidney graft failure. Cytokines are known
      to be important mediators in renal allograft outcome. The aim of the present
      study was to ascertain whether interleukin (IL)-4, IL-10, and transforming growth
      factor (TGF)-beta cytokine gene polymorphisms contributed to kidney graft
      outcome. We evaluated single nucleotide polymorphism in IL-4 (-1098G/T, -590C/T, 
      33C/T), IL-10 (-1082A/G, -819C/T, -592A/C), and TGF-beta (codon 10 and 25) in 100
      renal transplant recipients and 139 normal healthy control using polymerase chain
      reactions based on sequence-specific primers. Recipients were clinically
      characterized as rejection episode (RE) versus stable graft function (SGF). The
      results showed the frequencies of IL-4 -33 T allele in the RE, SGF, and control
      group to be 7%, 73%, and 28%, respectively. IL-10 -592 A allele frequency was 39%
      in RE, 26% in SGF, and 28% in the control group. TGF-beta codon 10 T allele was
      39% in RE, 35% in SGF, and 53% in control group. In conclusion, this study
      suggested that some cytokine gene alleles reflected SGF among kidney transplant
      recipients.

PMID- 17524862
TI  - Serum T-lymphocyte cytokines cannot predict early acute rejection in renal
      transplantation.
AB  - Despite numerous studies, the precise role of Th1/Th2 cytokines in acute renal
      allograft rejection remains unclear. To provide insight into the role of
      cytokines in acute allograft rejection, we measured serum T-cell cytokine
      concentrations for correlation with clinical events after renal transplantation
      in adults. Serum Th1 (interleukin-2 [IL-2] and interferon-gamma [IFN gamma] and
      Th2 (IL-4, IL-10) cytokine concentrations were measured in 60 consecutive living
      donor kidney transplant recipients namely, 40 males, overall mean age 38.82
      years), on the day before as well as 7 and 14 days posttransplantation using
      ELISA. Patients were stratified based upon acute rejection episode (ARE) in the
      first month after transplantation. Immunosuppression consisted of cyclosporine,
      mycophenolate mofetil, and prednisolone. ARE was diagnosed based on an increased
      plasma creatinine of more than 50%, sonographic analysis, radioisotope scan,
      pathologic findings, or measured cyclosporine blood levels. Twelve ARE were
      diagnosed among patients (20%). There was no significant difference between the 2
      groups with respect to the mean serum concentration values of IL-2, IL-10, IL-4,
      and IFN gamma on the day before or 7 or 14 days after transplantation. This study
      showed that there was no correlation between the Th1/Th2 serum cytokine profiles
      and early ARE in living donor kidney transplantation.

PMID- 17524863
TI  - Primary kidney disease and post-renal transplantation hospitalization costs.
AB  - BACKGROUND AND AIM: This study sought to assess posttransplantation
      hospitalizations costs in diabetic and nondiabetic subjects to see whether
      diabetes mellitus (DM) as a primary cause of end-stage renal disease (ESRD)
      increased posttransplantation hospitalization costs. METHODS: From 2000 to 2005,
      the hospitalization costs of 387 consecutive rehospitalizations of kidney
      recipients were retrospectively compared for two groups: patients with ESRD due
      to DM (n=71) and those with ESRD of non-DM etiologies (n=316). The
      hospitalization costs included the costs of hotel, medications, surgical
      procedures, paraclinical tests, imaging tests, health personnel time, special
      services (ie, patient transportation by ambulance), and miscellaneous costs.
      Societal perspective was used with costs expressed in PPP$ purchase power parity
      dollars (PPP$) estimated to be equal to 272 Iranian rials. RESULTS: Compared with
      the non-DM group, DM patients experienced significantly higher median costs both
      in total (1262 vs 870 PPP$, P=.001) and in cost components related to hotel (384
      vs 215 PPP$, P=.001), health personnel time (235 vs 115 PPP$, P<.001),
      paraclinical tests (177 vs 149 PPP$, P=.012), and special services (100 vs 74
      PPP$, P=.041). The mean of age was higher (P<.001), and the transplantation
      hospitalization time interval was also shorter in the DM group (median: 2.7 vs
      12, P=.025). CONCLUSIONS: Considering DM as a leading cause of ESRD and its
      increasing prevalence in some countries, the association between hospitalization
      costs of posttransplant patients and DM may be of great economic importance to
      many transplantation centers.

PMID- 17524864
TI  - Diabetes as the cause of end-stage renal disease affects the pattern of post
      kidney transplant rehospitalizations.
AB  - INTRODUCTION: Although there are reports that link diabetes-induced end-stage
      renal disease (ESRD) with several post renal transplantation complications and
      conditions, few studies have directly focused on this issue. This study compared
      the pattern of rehospitalizations after renal transplantation among diabetic
      versus nondiabetic ESRD patients, measuring causes, length of stay, outcomes and
      costs. METHODS: We retrospectively reviewed 366 randomly selected
      rehospitalization records of kidney transplant recipients between 1994 and 2006,
      including 69 who underwent renal transplantation due to diabetic nephropathy and
      297, due to nondiabetic ESRD. We compared the two groups with respect to
      demographic and clinical variables: donor source, readmission pattern,
      rehospitalization cause, time interval between transplantation and
      hospitalization (T-H time), length of hospital stay (LOS), and intensive care
      unit (ICU) admission, hospital charges, and inpatient outcomes of graft loss and
      mortality. RESULTS: The diabetes group, compared with nondiabetic group, had a
      greater mean age (53 +/- SD vs. 39 +/- SD years), proportion of admissions due to
      infections (44.9% vs. 32%) or renal dysfunction (14.5% vs. 29.6%), mean hospital
      charges ($5056 vs. $3046), and hospital mortality (18% vs. 4.3%; P<.05). Diabetic
      patients were readmitted sooner after transplantation than nondiabetic patients
      (11 vs. 18 months; P<.05). There was no difference between the groups with regard
      to gender, donor source, LOS, ICU admission, and graft loss. CONCLUSION: The
      etiology of ESRD should be considered for scheduling post renal transplantation
      follow-up. Renal transplant recipients with diabetes-induced ESRD need further
      attention in follow-up programs.

PMID- 17524865
TI  - Causes of rehospitalization after renal transplantation; does age of recipient
      matter?
AB  - BACKGROUND: This study assessed the causes and related factors of
      rehospitalization following renal transplantation among elderly compared with
      younger patients. METHODS: We reviewed the charts of 567 patients rehospitalized
      after kidney transplantation from 2000 to 2006. According to age at the time of
      transplantation, hospitalizations were divided into two groups: group 1 (age
      >or=50 years) and group II (age 20 to 50 years). Demographics, clinical findings,
      causes for rehospitalization, patient outcomes (recovery, graft loss, death),
      intensive care unit (ICU) admission, length of hospital stay, time interval from
      transplantation to rehospitalization, as well as hospital costs were compared
      between the two groups. RESULTS: One hundred eighty-five (32.6%)
      rehospitalizations were charted for group I, who showed a higher proportion of
      admissions due to infection (42.2% vs 29.8%, P=.004) and macrovascular disease
      (3.8% vs 1.0%, P=.027) compared with group II. ICU admission (8.8% vs 2.4%,
      P=.001), mortality (10.2% vs 3.6%, P=.008), and hospital charges (1610 +/- 933 vs
      931 +/- 850 purchase power parity dollars, P=.001) were also seen more frequently
      in group I but displayed a lower frequency of admissions due to graft rejection
      (20% vs 34.3%, P=.001). CONCLUSION: Recipient age at the time of transplantation
      was a main factor affecting rehospitalization among our patients.

PMID- 17524866
TI  - Prediction of inpatient survival and graft loss in rehospitalized kidney
      recipients.
AB  - INTRODUCTION: Despite a sizeable amount of research conducted hitherto into
      predictors of renal transplantation outcomes, there are scarce, data on
      predictors of in-hospital outcomes of post-kidney transplant rehospitalization.
      This study sought to provide a user-friendly prediction model for inpatient
      mortality and graft loss among rehospitalized kidney recipients. METHOD: This
      retrospective review of 424 consecutive kidney recipients rehospitalized after
      kidney transplantation between the years 2000 and 2005 used multiple logistic
      regression analysis to evaluate predictors of hospitalization outcomes. RESULTS:
      Multivariate analysis showed that age at admission, diabetes mellitus as the
      cause of end-stage renal disease (ESRD), admission due to cerebrovascular
      accident (CVA), surgical complications were predictors of in-hospital death; age
      at transplantation, surgical complications, and rejection were predictors of
      graft loss. Equation for prediction of in-hospital death was Logit(death) -0.304
      * age at transplantation (year) + 0.284 age at admission (year) + 1.621 admission
      for surgical complication + 4.001 admission for CVA-ischemic heart disease +
      2.312 diabetes as cause of ESRD. Equation for prediction of in-hospital death was
      Logit(graft loss) = 0.041 age at transplantation (year) + 1.184 admission for
      graft rejection + 1.798 admission for surgical complication. CONCLUSIONS: Our
      prediction equations, using simple demographic and clinical variables, estimated
      the probability of inpatient mortality and graft loss among re-hospitalized
      kidney recipients.

PMID- 17524867
TI  - Prolonged rehospitalizations following renal transplantation: causes, risk
      factors, and outcomes.
AB  - BACKGROUND: Although some studies have described rehospitalization after
      transplantation, few have focused on risk factors and consequences of prolonged
      hospital stay. Our goal was to determine the causes, risk factors, and outcomes
      of prolonged rehospitalizations after renal transplantation. PATIENTS AND
      METHODS: In this retrospective study, 574 randomly selected rehospitalization
      records of kidney transplant recipients were reviewed from 1994 to 2006.
      Admissions were divided into group 1, prolonged stay (length of stay >14 days,
      n=149), and group II, short stay (length of stay <or=14 days, n=425). Demographic
      data, cause of end-stage renal disease (ESRD), cause of readmission, ICU
      admission, time interval between transplantation and rehospitalization, costs,
      and in-patient mortality were compared between the two groups. RESULTS: Mean (+/
      SD) hospital stay was 10.6 +/- 9.8 days. Median hospital stay was 5 days for
      renal stones, 7 days for surgical complications, 8 days for malignancy, 9 days
      for infection, and 10 days for renal dysfunction. We found higher rates of ESRD
      due to diabetes in group I (28% vs. 15.4%; P=.006). Admissions due to infections
      (56.4% vs 42.4%; P=.003) or renal dysfunctions (55% vs 41.4%; P=.004) were the
      cause of higher proportions of total hospitalizations with prolonged stay.
      Prolonged stay also correlated with higher ICU admissions (8.8% vs 2.8%; P=.002)
      and mortality (6.7% vs 3.05%; P=.001). Mean total hospital cost for short versus
      prolonged hospitalizations were US$ 586 versus US$ 2750, respectively.
      CONCLUSION: In this study, we found that prolonged hospital stays accounted for
      >62% of all hospital costs; however, they comprised only 26% of the patients.
      High-risk kidney transplant recipients for prolonged hospitalizations should be
      closely observed for infections and graft rejection.

PMID- 17524868
TI  - Hospitalization databases: a tool for transplantation monitoring.
AB  - INTRODUCTION: We sought to account for changes in posttransplant hospitalization
      patterns in terms of the changes in demographic and transplantation-related
      variables. METHODS AND MATERIALS: We retrospectively analyzed 1860 cases of
      kidney transplantation performed between 1992 and 2004 in terms of demographic
      and transplantation-related variables. Of the 1860 cases, rehospitalization
      records in the first year posttransplantation were available for 1152 cases,
      which were assessed for causes of admission, mortality, graft loss, length of
      stay, and hospital charges. RESULTS: The pattern of rehospitalizations showed the
      following trends: (1) Increased rate of infection; (2) Decreased rate of graft
      rejection; and (3) Peak costs of rehospitalization between 1999 and 2000.
      CONCLUSION: We believed that the increased infection rate and decreased rejection
      rate may have been related at least partly to the shift in the treatment protocol
      from azathioprine-based to mycophenolate mofetil regimens in 2000. Furthermore,
      the peak in the relative frequency of diabetes mellitus and hypertension as the
      etiology of end-stage renal disease among those having undergone transplantation
      between 1999 and 2000 may have been responsible for the peak in rehospitalization
      costs and length of hospital stay. We are strongly of the opinion that hospital
      statistics are a valuable tool for health care policymakers to monitor
      transplantation outcomes.

PMID- 17524870
TI  - Cytomegalovirus disease after kidney transplantation: clues to accurate
      diagnosis.
AB  - BACKGROUND: The clinical diagnosis of cytomegalovirus (CMV) disease after kidney
      transplantation is often not accurate. We evaluated the factors associated with a
      correct diagnosis of CMV disease in these patients. MATERIALS AND METHODS: This
      retrospective study of all renal transplant patients between 2004 and 2005 with a
      clinical diagnosis of CMV disease included both donors and recipients who were
      seropositive for CMV at transplantation. We assessed the rate and correlated
      factors with a correct diagnosis. RESULTS: Among 127 cases, the 30 (23.6%)
      patients who had a correct diagnosis of CMV disease. Showed higher ages at
      transplantation (48.8 +/- 15.3 vs. 39.8 +/- 14.4 years; P=.004) and a shorter
      interval between transplantation and symptom presentation (9.7 +/- 20.7 vs. 25.6
      +/- 33.6 days; P=.048). Diabetes mellitus (DM) was the cause of end-stage renal
      disease (ESRD) in 41% of patients with a correct diagnosis, whereas it was the
      cause in 11% of CMV disease-negative patients (P<.001). A multiple logistic
      regression model showed that DM as the cause of ESRD (P=.001; odds ratio [OR]
      16.331), >5 months duration between transplantation and the presence of symptoms
      (P=.001; OR, 0.060), and age at transplantation >55 years (P=.022; OR, 3.833)
      were predictors of a correct diagnosis of CMV disease (chi(2)=46.45; P<.001).
      CONCLUSION: The results herein showed that considering some variables
      significantly improved the accuracy of a correct diagnosis of CMV disease after
      kidney transplantation.

PMID- 17524869
TI  - Clinical course of hepatitis C virus infection in renal transplant recipients.
AB  - Patients with end-stage renal disease are at high risk for exposure to hepatitis
      C virus (HCV) infection. Although both viral replication and liver disease
      progression are accelerated after renal transplantation, the long-term impact of
      chronic HCV infection is unclear. Our aim was to analyze the course of HCV
      infection in renal transplant recipients and the effects of HCV reactivation on
      patient and graft survival. METHODS: We retrospectively examined the 21-year
      (1985-2006) data of 1274 renal transplant recipients, 43 of whom were anti-HCV
      positive at the time of transplantation. RESULTS: The mean posttransplant follow
      up of 43 patients was 62.0 +/- 7.3 months. At the time of transplantation, HCV
      RNA was positive in 11 (25.6%) patients and negative in 32 (74.4%) patients. HCV
      reactivation was seen in 19 (45.2%) patients at a mean time of 20.8 +/- 5.7
      months. In 31 (72%) patients, acute rejection occurred, whereas graft loss
      occurred in 10 (23%) patients. Three (7%) patients died. Among 43 patients, 22
      (51.2%) were treated with interferon before transplantation. There was a
      statistically significant association between pretransplant interferon therapy
      and pretransplant HCVRNA level (P=.024), but no significant association of HCV
      reactivation and graft rejection, mortality, or kidney survival. CONCLUSION: HCV
      reactivation occurred in nearly half of the renal transplant recipients, mostly
      in the second year. Patient survival and graft survival were not affected by HCV
      reactivation. Anti-HCV positivity should not preclude chronic renal failure
      patients from renal transplantation.

PMID- 17524871
TI  - The association between cytomegalovirus infection and atherosclerotic events in
      renal transplant recipients.
AB  - Cytomegalovirus (CMV) infection is a risk factor for arteriosclerosis in renal
      transplant recipients. We sought to investigate the effects of CMV infection on
      atherosclerotic events (AE) in renal transplant recipients. This retrospective
      analysis included 200 patients: 52 women and 148 men of overall mean age of 36.18
      +/- 10.23 years who were transplanted at our center between 1998 and 2001. We
      analyzed demographic features, dialysis duration, diabetes, blood pressure level,
      body mass index (BMI), medications, and lipid parameters. CMV infection was
      diagnosed in 23.5% of patients in the first 2 years after transplantation; these
      patients were followed for 4 years. All patients had been assessed for AE,
      including previous myocardial infarction, angina, revascularization procedures,
      intermittent claudication, stroke, or transient ischemic attack. AE occurred in
      13% during the follow-up period. CMV infection was more frequent among these
      patients compared to those without AE, namely 42.3% versus 20.6%, respectively.
      Although the gender, dialysis duration, serum cholesterol level, presence of
      acute rejection, and BMI were not associated with AE, age, hypertension, and CMV
      infection did show a relation. A multivariate analysis by logistic regression
      revealed mean age and CMV infection to be independent risk factors for AE: odds
      ratio (OR)=5.6, 95% confidence interval (CI)=1.3 to 24.6 (P=0.02) and OR=4, 95%
      CI = 1.3 to 12.3 (P=.01). This study suggested that the presence of CMV infection
      may be a triggering factor for AE in renal transplant recipients.

PMID- 17524872
TI  - Clinical manifestation, laboratory findings, and the response of treatment in
      kidney transplant recipients with CMV infection.
AB  - OBJECTIVES: To report clinical manifestations, laboratory findings, and treatment
      outcomes of in kidney transplant recipients who had cytomegalovirus (CMV)
      infections. METHODS: This retrospective study evaluated the records of kidney
      transplant recipients followed regularly from 2001 to 2006. In some patients
      information was also gathered through a telephone call or physical examination.
      The CMV infection diagnosis was also made by detecting PP.65 antigen per 50,000
      peripheral blood leukocytes. RESULTS: Of the 200 kidney transplant recipients, 66
      were infected with CMV including 42 men and 24 women. The mean patient age was 40
      +/- 13 years (range, 14 to 67 years). Seventy-nine percent of the infected
      patients were diagnosed during the first 6-months after transplantation. All
      except 22 patients (33%) had constitutional complaints. Fever was present in 65%
      of patients, abdominal pain in 21%, diarrhea in 20%, and vomiting in 15%.
      Likewise, pulmonary complaints including cough and dyspnea were reported by 32%
      and 23%, respectively. However, 20% of patients were completely asymptomatic.
      Hematologic laboratory data showed anemia (64%), thrombocytopenia (47%), and
      leukopenia (21%). Seventy eight percent of patients had a serum creatinine <or=2
      mg/dL before infection, but it was <or=2 in just 26% at the time CMV was
      diagnosed and 60% after treatment. Antiviral therapy included intravenous
      gancyclovir in 80% of patients and gancyclovir plus oral acyclovir in 20%.
      Corticosteroid pulse therapy was also administered in 78% of patients. No
      statistically significant correlation was observed between CMV antigen load and
      the severity of clinical manifestations or the time of response to treatment or
      the recurrence prognosis. In our series, 1 patient died, 28 treated patients
      (42%) experienced CMV recurrence, and 37 (56%) showed no recurrence. CONCLUSIONS:
      CMV infection should be considered in any renal transplant recipient who has a
      rise in creatinine even if symptom-free. Despite the results of other studies, we
      found no prognostic value for the viral antigen load.

PMID- 17524873
TI  - Oral valgancyclovir versus intravenous gancyclovir for cytomegalovirus
      prophylaxis in kidney transplant recipients.
AB  - BACKGROUND: Prophylaxis against cytomegalovirus (CMV) is a regular practice in
      organ transplantation. Oral valgancyclovir appears to be an interesting
      alternative to the usual intravenous form. PATIENTS AND METHODS: We prospectively
      compared the response of intravenous gancyclovir for 2 weeks (GAN; n=41) to oral
      valgancyclovir for 2 weeks (VAL2w; n=23) or 3 months (VAL3m; n=46) in kidney
      transplant recipients receiving induction immunosuppression. CMV antigenemia
      assay and/or polymerase chain reaction (PCR) were used for viral detection.
      Patients were followed for a minimum of 6 months posttransplantation. SPSS
      software was used for statistical analysis using a cutoff of significance as
      P<.05. RESULTS: There was no statistical difference in the demographic features
      among the study groups. However, human leukocyte antigen (HLA) match was better
      in the VAL3m group and the patients of this group received less ATG induction
      immunosuppression (41.3%) compared with the GAN group (100%). The incidence of
      acute rejection was not different among the study groups. There was a higher
      incidence of fever with positive CMV tests in the VAL2w group (P=.035) compared
      with the other groups, while leukopenia with a negative CMV test was
      significantly higher in the VAL3m group (P=.04). The incidence of CMV disease was
      higher in the VAL2w group (30.4%) compared with the GAN group (14.6%) or the
      VAL3m group (8.7%). Renal function was significantly worse in the VAL2w group at
      3 and 6 months (P=.011 and .02, respectively). CONCLUSIONS: Three months oral
      valgancyclovir prophylaxis for CMV was a more effective regimen compared with
      intravenous gancyclovir for 2 weeks. Shorter courses were associated with a
      higher incidence of CMV infection and poorer graft function. Leukopenia observed
      in patients receiving valgancyclovir may be a drug-related side effect.

PMID- 17524874
TI  - Seroprevalence of human herpes virus-8 in renal transplant recipients: a single
      center study from Iran.
AB  - The long-term risk of malignancy among renal transplant patients is approximately
      100 times that of the general population. Unlike North America and many European
      countries, Kaposi's sarcoma is the most common cancer after renal transplantation
      in most series reported from the Middle East. Human herpes virus-8 (HHV-8) has a
      major role in the pathogenesis of Kaposi's sarcoma. The risk of
      posttransplantation Kaposi's sarcoma is 23% to 28% among seropositive patients
      compared with 0.7% among seronegative patients. This study was conducted to
      investigate the seroprevalence of HHV-8 among our transplant recipients. The sera
      from 100 renal transplant recipients were examined by indirect immunofluorescence
      against latent nuclear antigen. Sixty of 100 patients were males. The overall
      mean age was 41.1 years (range, 17-74 years) with 17 patients older than 55
      years. The mean transplantation duration was 41.6 months. Twenty-five percent of
      patients were seropositive for HHV-8. There was statistically significant
      seropositivity for HHV-8 among recipients older than 55 years (P=.02). Eight of
      17 patients older than 55 years were seropositive (47%), whereas 17/83 patients
      younger than 55 years were seropositive (20%). There were no significant
      differences for HHV-8 seropositivity regarding sex, transplantation duration, and
      immunosuppressive regimen, including dose of immunosuppressive drugs and
      cyclosporine blood levels. In this study, we showed seropositivity for HHV-8
      among a significant percentage of our renal transplant recipients, a finding
      which may render them at risk to develop Kaposi's sarcoma. Seropositive and
      seronegative patients were followed for 16 months. One HHV-8 seropositive patient
      (1/25) developed Kaposi's sarcoma.

PMID- 17524875
TI  - Gastro-duodenal lesions and Helicobacter pylori infection in uremic patients and
      renal transplant recipients.
AB  - BACKGROUND: Upper gastrointestinal (UGI) symptoms are common in uremic patients,
      and higher serum levels of urea have been suggested to be related to Helicobacter
      pylori (HP) colonization and UGI mucosal inflammation. AIM: The aim of this study
      was to compare HP infection and UGI endoscopic findings between uremic patients,
      renal transplant (RT) recipients, and controls. METHODS: A total of 474 subjects
      (71 chronic renal failure [CRF], 73 hemodialysis [HD], 25 Tx, and 305 controls)
      from Baqyiatallah Hospital, Tehran, Iran were recruited between April 2002 and
      March 2004 for evaluation of dyspepsia, excluding those receiving any HP
      eradication therapy. All subjects were examined for esophagus, stomach and
      duodenum mucosa, and infection with HP on 2 distinct tissue samples of the
      anthral region. RESULTS: Four groups of subjects (mean +/- 2 se; age, 45 +/- 1.6
      years; 62.9% male) were studied. Duodenal ulcer in the uremic patients (CRF,
      16.1%; HD, 13.7%) was more common than that in the RT-recipients (8%) and
      controls (6.5%); P=.038. Erosive gastritis and duodenal bulb deformity were also
      more common in the uremic subjects (CRF, 23.9%, 36.9%; HD, 30.1%, 20.5%,
      respectively) than those in the other subjects (RT recipients, 16%, 8%; controls,
      8.2%; 0%, respectively); P<.001. HP infection was found to be higher in the
      uremic patients (CRF, 66.2%; HD, 63%) than in the RT recipients (40%) and
      controls (34.8%); P<.001. CONCLUSION: Higher rates of gastric and duodenal
      mucosal lesions and HP infection in the uremic patients in comparison with the
      subjects with normal renal function may have resulted from higher serum levels of
      urea, anemia, and fluctuations in the gastric blood supply in the CRF and HD
      patients. However, more tenable evidence from controlled trials is required for
      the eradication of HP in all uremic patients and transplantation candidates.

PMID- 17524876
TI  - Tuberculosis in Iranian kidney transplant recipients: a single-center experience.
AB  - INTRODUCTION: Renal transplantation recipients are at a high risk of developing
      tuberculosis (TB) following transplantation, especially in developing countries,
      with high incidences of morbidity and mortality. In this report, we examined the
      risk factors and impact of TB on the outcome of kidney transplantation. PATIENTS
      AND METHODS: Among 1350 living donor Iranian kidney transplantations, 52 (3.9%)
      had TB diagnosed in various organs. Of these, 7 (13.5%) had TB pretransplantation
      and 40 (76.9%) were men. The overall mean age was 32.6 +/- 10.5 years. RESULTS:
      The interval between transplantation and diagnosis was 54.6 +/- 48.23 (range 4 to
      140) months. In 34 (65.6%) patients TB was diagnosed after the first year
      posttransplantation. Pleuro/pulmonary TB was the most common form (68%). All
      posttransplant TB patients received a quadriple antituberculosis therapy;
      pyrazinamide, rifampicin, ethambutol, and isoniazide). Hepatotoxicity was seen in
      16 (30%) patients, including 12 mild cases with normalization after temporary
      withdrawal of isoniazide and rifampicin, and four were severe, but mortality was
      not attributable to hepatocellular failure. Twelve patients (23%) died. Chronic
      allograft dysfunction occurred in 34 (65%) patients, 19 (37%) with graft loss.
      Pre-TB patients showed comparable posttransplant courses. CONCLUSION: TB is a
      common infection among renal transplant recipients in developing countries. The
      peak incidence is after the first year of transplantation and mortality is
      considerable. Hepatoxicity is a considerable risk of treatment, possibly as a
      result of additive toxic effects of immunosuppressive drugs. Chronic allograft
      nephropathy is a serious complication that has a negative impact on the graft
      survival.

PMID- 17524877
TI  - Tuberculosis after renal transplantation.
AB  - Tuberculosis (TB) remains a major public health problem in our country. Its
      diagnosis in immunodeficient patients is difficult. In this retrospective study,
      we analyzed the prevalence, clinical presentation, and outcome of TB after renal
      transplantation (RT) in our Tunisian team's experience. Among 359 renal
      transplant recipients, 9 (2.5%) developed TB at 49.6 months (range, 3-156 months)
      after RT. There were 7 men and 2 women of mean age 37.8 years (range, 15-53
      years). The organs involved included lymph nodes in 1 case; lung in 5 cases;
      genitourinary system in 1 case; rachis in 1 case; pleural in 1 case; and both
      pulmonary and urinary systems in 1 case. The diagnosis was bacteriologic in 6
      cases; histologic in 1 case; and 2 patients had a high index of suspicion. All
      patients were treated with a combination of rifampicin, isoniazide, pyrazinamide,
      and ethambutal. Recurrence of TB infection was noted in 3 cases with multiple
      localizations: lymph node, muscle abscess, meningitis, genitourinary system,
      rachis, and lung. Two patients died. In conclusion, among renal transplant
      patients, extrapulmonary involvement and recurrence of TB were frequent.

PMID- 17524878
TI  - Hyperinfection strongyloidiasis: an anticipated outbreak in kidney transplant
      recipients in Kuwait.
AB  - BACKGROUND: Hyperinfection strongyloidiasis is a potentially fatal syndrome
      associated with conditions of depressed host cellular immunity. A high degree of
      suspicion is required to detect cases early and thereby avoid a fatal outcome.
      PATIENTS AND METHODS: Three consecutive cadaveric kidney transplant recipients
      died within 2 months from hyperinfections with strongyloides. All members of the
      transplant team were involved in a campaign to localize the source of infection,
      identify and treat affected patients, and provide adequate prophylaxis to other
      transplant recipients. We reviewed cadaveric donor files and screened 61 hospital
      personnel, 27 hospital inpatients, and the 87 hospital outpatients transplanted
      in a year's time before that event for a possible source. The screening test
      included analysis of fresh stool samples on 3 consecutive days for strongyloides
      larvae. The anti-helminthic drug albendazol was administered to all patients
      during screening. They were followed for possible development of the disease
      during the infectivity period. RESULTS: The first 2 recipients received their
      kidneys from 1 cadaveric donor, while the third received it from a different
      donor. Both donors came from areas endemic for strongyloidiasis. The 3 recipients
      were on tacrolimus-based immunosuppression. The twin recipient of the second
      kidney was on cyclosporine and did not manifest a disease. All stool samples
      taken for screening were negative for the infective larvae. None of the other
      recipients developed the disease. CONCLUSIONS: Cadaveric donors were the possible
      source for this outbreak. Cyclosporine probably has a protective effect against
      strongyloides. In our setting, screening of cadaveric donors for strongyloides is
      mandatory before accepting them for donation, and oral prophylaxis is required
      for all recipients.

PMID- 17524879
TI  - Urinary tract infections in renal transplant recipients.
AB  - Urinary tract infection (UTI) is the most common infectious complication
      following renal transplantation. The purposes of this study were to determine the
      causative agents of UTIs among renal transplant recipients and to compare the
      antibiotic susceptibilities of Escherichia coli strains isolated from renal
      transplant recipients and complicated community-acquired UTIs. We evaluated 75
      episodes of 63 recipients with confirmed UTI who underwent transplantation during
      the period 1981 to 2006 at our center. Medical records of the patients were
      reviewed retrospectively. To compare the susceptibility rates of E coli, 226
      isolates from nontransplant patients with complicated community-acquired UTIs
      were also evaluated. Ten episodes (13.3%) occurred in the first month following
      the transplantation, 11 (14.7%) in the period of the second month to the sixth
      month, and 54 (72%) after the sixth month of transplantation. Forty-six (61.3%)
      isolates were E coli. Among these isolates, ciprofloxacin resistance rates were
      50% (2/4) in the first month after transplantation, 75% (6/8) in the period of
      the second month to the sixth month, and 32.4% (11/34) beyond 6 months after
      transplantation. The resistance rates of trimethoprim/sulfamethoxazole (TMP-SMX)
      in the same time periods were 100% (4/4), 87.5% (7/8), and 70.6% (24/34),
      respectively. The rates of resistance to TMP-SMX among E coli isolated from renal
      recipients were significantly higher than those in community-acquired complicated
      UTIs. The increased resistance of urinary pathogens to this agent is a major
      concern. Although high resistance rates of ciprofloxacin against E coli strains
      were determined in this group, it was not found to be statistically significant.

PMID- 17524880
TI  - Renin-angiotensin system polymorphisms and hemoglobin level in renal allografts:
      a comparative study between losartan and enalapril.
AB  - INTRODUCTION: In this study, hemoglobin (Hb) concentrations secondary to
      enalapril (E) or losartan (L) therapy were evaluated with respect to renin
      angiotensin system (RAS) polymorphisms in renal transplant recipients. MATERIALS
      AND METHODS: After determination of RAS polymorphisms [angiotensin-converting
      enzyme (DD, non-DD), angiotensinogen (TT, non-TT), and angiotensin receptor type
      1 (CC, non-CC)] by polymerase chain reaction, 70 renal transplant recipients were
      recruited to four groups randomly: first and second groups were treated with E
      (10 mg/d, 15 patients) and L (50 mg/d, 20 patients) alone, respectively. The
      third group received E+L (10 mg/d + 50 mg/d, 13 patients) and the fourth group
      (22 patients) received no medication. The treatment protocol was followed for 16
      weeks. Complete blood counts were checked before treatment and every 2 months.
      P<.05 was considered to indicate statistical significance. RESULTS: Treatment for
      4 months decreased the Hb level in the E+L (14.15 +/- 0.94 to 12.06 +/- 0.66
      g/dL, P=.000), E (14.00 +/- 0.86 to 13.11 +/- 0.82 g/dL, P=.02), and L (14.12 +/-
      0.90 to 12.10 +/- 2.35 g/dL, P=.01) groups, but not in the control group (13.55
      +/- 0.70 to 13.36 +/- 0.69 g/dL, P>.05). None of these regimens showed greater Hb
      reduction than the others (P>.05). None of the RAS polymorphisms predicted the
      intensity of the reduced Hb according to the type of treatment (P>.05). Any other
      sets of RAS polymorphisms (alone or together) did not impact on Hb levels pre- or
      post-intervention (P>.05). CONCLUSION: Our findings suggest that low dosages of E
      and/or L decrease Hb levels regardless of the RAS polymorphisms.

PMID- 17524881
TI  - Is uric acid a predictive factor for graft dysfunction in renal transplant
      recipients?
AB  - Hyperuricemia is a common complication in renal transplant recipients, and uric
      acid (UA) may play a role in renal dysfunction. The aim of this study was to
      evaluate the effects of UA on chronic allograft nephropathy (CAN) in renal
      transplant recipients. The 133 study subjects included 34 women and 99 men of
      overall mean age of 34.7 +/- 9.9 years. They underwent renal transplantation
      between 1998 and 2000. Serum UA levels were measured in the first month after
      transplantation and then at yearly intervals throughout a 3-year follow-up. In
      the first month after transplantation, 55.3% of recipients had hyperuricemia (UA
      >7 mg/dL in men; UA >6 mg/dL in women), but, 3 years after transplantation, 84.6%
      of the subjects had that disorder (P<.001). CAN was diagnosed in 31.5% of the
      patients at a mean onset of 31.8 +/- 14.3 months after transplantation. Fifty-two
      percent of these individuals experienced graft failure within 43.3 +/- 20.8
      months after transplantation. UA levels were recorded before the development of
      CAN. There was no association between UA levels and CAN according to a Cox
      regression analysis (P>.05; relative risk, 1.082; 95% confidence interval [CI]
      0.9-1.3). We concluded that the prevalence of hyperuricemia was higher among
      recipients than in healthy individuals, but that the UA level did not affect the
      development of CAN during first 3 years after transplantation.

PMID- 17524882
TI  - Effects of renal transplantation on serum-free and total PSA levels.
AB  - PURPOSE: This study was undertaken to evaluate the effects of renal
      transplantation on serum level of free and total PSA. MATERIALS AND METHODS: In
      this study, we included 30 male patients with a mean age of 46 years with end
      stage renal disease undergoing renal transplantation at our department. None of
      the patients had any history of prostate cancer. All patients had immediate onset
      of renal function after transplantation, defined by a spontaneous decrease in
      serum creatinine on postoperative day 1 and a subsequent decrease daily during
      week 1. Renal transplantation included living-related donors in all patients.
      Blood samples were obtained before and at posttransplant day 6 before removal of
      Foley catheter. Measurements of free PSA and total PSA were performed with
      immunofluorometric assays. Glomerular filtration rates were monitored by
      analyzing serum creatinine. The significance of changes with time was estimated
      by the Wilcoxon signed ranks test for paired observations with P<.05 considered
      statistically significant. RESULTS: The mean free and total PSA levels before
      transplantation were 0.22 (range, 0.0.05 to 0.4) and 1.5 ng/mL (range, 0.1 to
      2.9), respectively. There was a significant decrease (30% of original levels) in
      serum fPSA at posttransplant day 6 (P<.05) in all patients. There was no
      significant changes of total PSA at posttransplant day 6. CONCLUSIONS: These
      results verify the hypothesis that free PSA is eliminated from the blood
      circulation by glomerular filtration and severe renal failure influences its
      levels. Thus, we should consider different cutoffs for free to total ratio before
      and after renal transplantation.

PMID- 17524883
TI  - Does renal transplantation improve erectile dysfunction in hemodialysed patients?
      What is the role of associated factors?
AB  - OBJECTIVE: To assess the effect of successful renal transplantation on
      improvement of erectile function in hemodialysis (HD) patients and the
      relationship between the degree of patient response and other factors. MATERIALS
      AND METHODS: From September 2002 to November 2005, erectile function of 64
      patients on HD for at least 6 months was evaluated pretransplantation and 6
      months posttransplantation by International Index of Erectile Function, version 5
      (IIEF-5). Sixty four age-matched persons without renal impairment were enrolled
      as control group to compare erectile dysfunction (ED) prevalence with the HD
      group. We evaluated duration of HD, age, and site of arterial anastomosis. In an
      attempt to find predictors of improvement of ED, after kidney transplantation, we
      performed linear regression analysis with a backward method. RESULTS: The
      prevalence of ED in HD patients was 87.5%. Although there were some differences
      in the prevalence of ED between patients older versus younger than 50 years, the
      difference was not statistically significant. There was no relationship between
      the duration of dialysis and the severity of ED in HD group. Compared to the
      pretransplant IIEF-5 score (13.59), there was significant improvement (19.16). In
      an attempt to find predictors of ED improvement, we used a linear regression
      analysis with backward method. Pretransplant IIEF-5 score, age at the time of
      transplant, and anastomosis to the common iliac artery showed significant
      associations with improvement, but the duration of dialysis and anastomosis to
      internal iliac or external iliac artery did not. CONCLUSION: The incidence of ED
      among hemodialyzed patients is high. Kidney transplantation is the key treatment
      for this complaint. ED has a major negative impact on the quality of life and
      family relations. Its treatment is associated with improvement of psychogenic
      factors. ED is a sensitive topic and many patients will not spontaneously discuss
      it with their physician, so better to include potency evaluation in
      posttransplantation list evaluations.

PMID- 17524884
TI  - Calcium and phosphorus metabolism disturbances after renal transplantation.
AB  - INTRODUCTION: Several studies have noted that, despite beneficial correction of
      abnormalities of mineral metabolism after successful renal transplantation, renal
      functional recovery is incomplete. Also, persistence of hyperparathyroidism and
      metabolic acidosis among patients with chronic impairment of graft function
      together with the use of loop diuretics and immunosuppressive drugs with adverse
      effects may alter mineral metabolism. We determined calcium and phosphorus levels
      in recipients. METHODS: This cross-sectional study enrolled 398 recipients in 2
      medical centers in Iran from 1988 to 2004 to evaluate serum calcium and
      phosphorus levels after 1 month in relation to graft and patient survivals.
      Cyclosporine was the constant part of the immunosuppressive treatment in all
      study subjects. RESULTS: The median follow-up time was 8 months (range, 1-180
      months). One and 10-year survival rates of patients were 97.9% and 91.1%. Mean
      (SD) serum calcium levels before and after transplantation were 8.79 (1.26) and
      8.50 (1.39) mg/dL, respectively (P=.020). The mean (SD) phosphate levels before
      and after transplantation were 6.43 (2.42) and 3.64 (1.71) mg/dL, respectively
      (P=.000). There was no significant difference in survival considering changes in
      serum calcium and phosphorus levels. There was no correlation between serum
      calcium and phosphorus level changes among study patients. CONCLUSIONS: Despite
      reports suggesting hypercalcemia as a posttransplantation finding, we did not
      observe this condition, but, consistent with other reports in this field, we
      observed a significant decrease in serum phosphorus levels showing correction of
      this mineral level.

PMID- 17524885
TI  - Avascular osteonecrosis after renal transplantation.
AB  - Avascular osteonecrosis (AVN) is a serious osseous complication after renal
      transplantation. Its prevalence clearly decreased from 20% to 4% after
      introduction of cyclosporine and reduction of steroid doses. The aim of our study
      was to evaluate the frequency of AVN among kidney transplant recipients and to
      determine the risk factors by comparing them with a population without AVN. Among
      326 kidney transplant recipients between June 1986 and December 2004, 15 patients
      developed AVN with mean age of 40.86 years, including 11 men and 4 women. Fifteen
      kidney transplant recipients without AVN were selected to be matched for age,
      gender, and date of transplantation (control group). Cases of symptomatic AVN
      were diagnosed by hip X-ray, radioisotope bone scan, or magnetic resonance
      imaging. AVN was diagnosed at a mean of 3.5 years after transplantation (range,
      0.5-13 years). The main localization of AVN was the femoral head in 12 cases and
      the femoral condyle in 3 cases. We studied the following risk factors: the type
      of donor (cadaver or living donor), the duration on dialysis before
      transplantation, the cumulative steroid dose, the acute rejection rate, and the
      posttransplantation weight gain. Statistical analysis showed that the cumulative
      steroid dose and the acute rejection rate were higher among the AVN group than
      the control group (P=.04 and P=.058, respectively). The prevalence of AVN in our
      population is 4.6%, which is probably an underestimate since these were
      symptomatic cases. The reduction or early withdrawal of steroids remains the only
      efficient preventive treatment for AVN.

PMID- 17524886
TI  - Bone mineral density changes within 11 months of renal transplantation in Iranian
      patients.
AB  - BACKGROUND AND AIM: We studied bone mineral density (BMD) changes in Iranian
      patients with end-stage renal disease (ESRD) within 11 months after renal
      transplantation. METHODS: Among 68 ESRD candidates for renal transplantation, the
      BMD at the femur and the spine were assessed using a DEXA Norland scanner. Linear
      regression analysis was used to identify risk factors associated with low bone
      density. RESULTS: Mean BMD, T-score and Z-score of femur and spine were
      significantly reduced (at femur, 0.78 +/- 0.14, -2.4 +/- 1.1, -1.6 +/- 1.0; at
      spine, 142.25 +/- 105, -1.09 +/- 1.1, -1.07 +/- 0.9). Osteoporosis and osteopenia
      were found 55.2% and 36.2% at the femur and 8.6% and 58.6% at the spine,
      respectively. The BMD showed a significant negative association with age
      (r=0.615), female gender (r=0.394), and corticosteroid intake (r=0.286), and a
      positive association with weight (r=0.394) and body mass index (r=0.626). There
      was no significant association between BMD measurements and calcium, phosphorous,
      or parathyroid hormone levels. At 11 months follow-up, in 20 patients, the
      subject had lost a mean of 2.4% T-score and 2.8% Z-score at spine (P=.027 and
      .13, respectively), but did not experience significant declines at the femur. BMD
      showed a decrease in 80% of recipients in the spine area; there was a 15% BMD
      increase at the hip. CONCLUSION: Low bone density is common among ESRD Iranian
      patients. Early screening and treatment of this group is recommended. Significant
      loss in lumbar density occurred within 11 months of transplantation in more than
      one third of a prospective cohort of renal transplant recipients.

PMID- 17524887
TI  - Hyperlipidemia after renal transplantation and its relation to graft and patient
      survival.
AB  - INTRODUCTION: Hyperlipidemia is a multifactorial event that frequently develops
      following renal transplantation and may worsen the patient's prognosis. The aim
      of this study was to evaluate the incidence and concomitant factors for
      hyperlipidemia. METHODS: We studied 687 renal transplant recipients from 1988 to
      2004 using a cross-sectional design to determine the frequency of
      hypercholestrolemia and hypertriglyceridemia before and 1 month to 1 year after
      renal transplantation, to evaluate its relation to patient and graft prognosis in
      two medical centers in Iran. Cyclosporine was the constant part of
      immunosuppressive treatment in all study subjects. RESULTS: One and 5-year graft
      survival times were 94.23% and 81.34%, respectively. The prevalence of
      hypercholestrolemia after transplantation was 59.9%. Mean (+/- 2 SE) serum
      cholesterol levels before and after transplantation were 161.15 +/- 3.81 and
      213.83 +/- 4.53 mg/dL respectively (P=.000). Triglycerides levels, were 159.99 +/
      13.08 and 196.28 +/- 19.6 mg/dL respectively. There was no significant
      correlation between cyclosporine dose, graft and patient survivals, and severity
      of hyperlipidemia (determined by cholesterol and triglyceride levels).
      CONCLUSIONS: Lipid metabolism abnormalities observed in this study were similar
      to other reports. There was no correlation with patient or graft survival. In
      addition, there may routes for development of hyperlipidemia other than adverse
      complications of immunosuppressive drugs.

PMID- 17524888
TI  - Medical comorbidities after renal transplantation.
AB  - BACKGROUND: Despite the amount of evidence regarding the negative impact of
      medical comorbidities after transplantation, little attention has been directly
      paid to the pattern of somatic comorbidities in renal transplant recipients. The
      aim of this study was to assess the prevalence of medical comorbidities after
      kidney transplantation. METHODS: In a cross-sectional study during 2006, we
      evaluated 119 kidney transplant recipients for somatic comorbidities by using the
      Ifudu comorbidity index, which evaluated the presence of 14 chronic illnesses
      among patients undergoing maintenance hemodialysis. Correlations of the Ifudu
      score with demographic and clinical data were also studied. RESULTS: Eighty-three
      (90.4%) subjects had at least one medical comorbidity. The mean comorbidity score
      was 5.17 +/- 4.50. The most frequent comorbidities were nonischemic heart
      diseases including hypertension (n=75; 63%), visual disturbances (n=42; 35.2%),
      low back pain and spine and joint disorders (n=30; 25.21%), and musculoskeletal
      disorders (n=28; 23.5%). A higher comorbidity score was significantly correlated
      with lower economic status (P<.05), but not with age, gender, marital status,
      educational level, cause, or duration of end-stage renal disease. CONCLUSION: The
      prevalence of medical comorbidities among kidney transplant recipients seems to
      be high, with the highest prevalence due to nonischemic heart diseases, visual
      disturbances, and musculoskeletal disorders. This highlighted the necessity of
      providing posttransplant care by a multidisciplinary team of specialists.

PMID- 17524889
TI  - Serum erythropoietin levels and their correlation with the erythropoietic system
      in hemodialysis patients and renal allograft recipients.
AB  - BACKGROUND: Following renal transplantation, serum erythropoietin (EPO) levels
      gradually increase during the first 2 to 3 months. However, some transplant
      recipients continue to remain anemic. The aim of the present study was to
      correlate serum EPO concentrations with hematocrit (Hct) and hemoglobin (Hb)
      levels in hemodialysis (HD) patients and renal allograft recipients. METHODS: In
      a comparative cross-sectional study, serum EPO concentrations and Hb and Hct
      levels were measured in 35 chronic HD patients and 40 transplant recipients who
      had stable kidney function for at least 6 months after transplantation (group 1).
      The HD patients were further divided based on their recombinant human (rHu) EPO
      supplementation into those who received rHu EPO during dialysis (group 2A, n=15)
      and those who were not on rHu EPO (group 2B, n=20). Data are presented as mean
      values +/- SD. The statistical analysis was performed by SPSS version 11.0 using
      chi-square, ANOVA, and Pearson correlation tests. A general linear model (GLM)
      was used to compensate for the effects of age. The P value for significance was
      set at .05. RESULTS: Group 2B patients tended to be older than groups 1 and 2A
      (P=.014). The sex ratios were comparable among groups. Mean EPO level was 17.09
      +/- 10.99 mIU/mL in recipients, which was comparable with that of HD patients
      (18.54 +/- 26.18 mIU/mL; P>.05). No significant correlation was observed between
      the serum EPO concentrations and Hb and Hct levels in recipients (P>.05). When
      comparing the 3 groups, EPO was not correlated with Hct and Hb in any group. Hb
      and Hct were significantly higher among HD patients not on rHu EPO therapy
      (P=.02). GLM, with age as a covariate, did not yield a significant difference
      between EPO levels of the studied groups (P=.36). CONCLUSIONS: This study showed
      that serum EPO level was in the normal range in recipients and HD patients. We
      were not able to find any correlation between Hb and Hct levels and EPO
      concentrations in any group of patients irrespective of rHu EPO supplementation.
      Hence, impaired EPO stimulatory effects may be considered a potential contributor
      to anemia in these patients.

PMID- 17524890
TI  - The outcome of diverticulosis in kidney recipients with polycystic kidney
      disease.
AB  - INTRODUCTION: Diverticulosis is a common finding in autosomal-dominant polycystic
      kidney disease (ADPKD). To avoid the serious complications of diverticulosis
      after kidney transplantation, some policies have recommended aggressive actions,
      such as elective colectomy. These policies are not widely agreed upon. This
      controversy led us to investigate the serious complications and the outcome of
      diverticulosis in ADPKD kidney recipients to see whether such therapies are
      justified. MATERIALS AND METHODS: From 2002 to 2006, we followed 18 ADPKD kidney
      recipient patients with barium enema-documented diverticulosis. All subjects were
      asymptomatic for diverticulosis at the time of transplantation. The mean value +/
      SD of follow-up duration was 25.4 +/- 28.5 months. We documented demographic
      data, familial history of ADPKD, barium enema findings, and complications as well
      as graft and patient survivals. RESULTS: Hepatic flexure was the most prevalent
      site for diverticula. The mean (SD) of diverticular count was 6 +/- 5.1. Patients
      with a familial history of ADPKD showed a higher number of diverticular (P=.01).
      Diverticulitis occurred in three patients, all of whom died. CONCLUSION:
      Diverticulitis is a fatal and not rare complication in ADPKD patients. The rate
      of complications in our study was similar to previous findings, but we observed
      serious complications even among patients asymptomatic at the time of
      transplantation. The decision to take aggressive action such as elective
      colectomy is still a matter of debate that needs further evaluation.

PMID- 17524891
TI  - Evaluation of posttransplantation malignancies compared with de novo tumors.
AB  - It is uncertain whether tumors arising in transplant patients resemble ones that
      develop de novo in pathogenesis, morphology, and behavior. This study sought to
      investigate some clinical, morphological, and immunohistochemical features of
      several posttransplantation malignancies compared with similar de novo tumors.
      The study group consisted of 40 malignant tumors encountered in 1350 transplant
      patients (1229 kidneys, 113 livers, 8 hearts) between 1986 and 2006. Tumors with
      3 or more examples were compared with randomly selected controls. These included
      Kaposi's sarcoma (n=14); extranodal lymphoma (n=9); squamous cell carcinoma
      (n=6); and nodal lymphoma (n=3). The variables that were analyzed were the
      localization, predisposing lesions, degree of differentiation, and host response.
      For lymphomas, we also determined histological subtype, origin, and Ki-67
      proliferation index. Most tumors (36/40, 90%) occurred in patients with renal
      transplants. However, the relative frequency was higher among liver transplant
      cases (3.53% vs 2.92% for kidney transplants). No malignancy was seen in heart
      transplant cases. Squamous cell carcinomas were better differentiated (P<.05)
      compared with controls and they were more frequently associated with precursor
      lesions (P<.05). Kaposi's sarcomas involved internal organs more frequently in
      posttransplant patients, and the Ki-67 proliferation index was higher in
      posttransplantation nodal lymphomas. However, these factors were not
      significantly different (P>.05). Our findings suggested that certain
      posttransplantation malignancies display unique characteristics compared with
      their de novo counterparts.

PMID- 17524892
TI  - Recurrent multiple myeloma following renal transplantation: a case report.
AB  - Renal transplantation is generally not considered for patients with multiple
      myeloma (MM) because of their extremely poor prognosis. However, for patients in
      remission, it offers an alternative to dialysis. There are few reports of MM
      recurrence among kidney transplant recipients. We report a 57-year-old white man
      with end-stage renal disease (ESRD) and known multiple myeloma in remission who
      underwent kidney transplantation. Eighteen months after transplantation upon
      routine follow-up, he was observed to have an elevated creatinine with no
      evidence of recurrence of myeloma upon bone marrow aspiration. Light microscopy
      and immunofluorescence of a renal biopsy showed chronic scarring of the kidney
      owing to cast nephropathy consistent with MM recurrence. Repeat bone marrow
      aspiration 1 week later confirmed this diagnosis. A review of the literature of
      prior studies suggested that it is reasonable to perform renal transplantation in
      patients with ESRD due to MM in remission, but large prospective studies would
      help to develop a strategy for prevention of multiple myeloma recurrence.

PMID- 17524893
TI  - Abdominal computed tomography findings of malignant tumors in patients with solid
      organ transplants.
AB  - AIMS: Incidence of malignancy in solid organ transplant recipients is higher
      compared to the general population. The aim of this study was to characterize
      distribution and appearance of abdominal malignant tumors detected with spiral
      computed tomography (CT) examination in patients with solid organ
      transplantation. MATERIALS AND METHODS: Between July 1994 and April 2006, 198
      patients underwent liver transplantation and 568 patients underwent renal
      transplantation in our center. The abdominal CT studies were reviewed to
      determine the presence or absence of abdominal malignancy. All abdominal CT
      examinations were performed prior to immunomodulation or chemotherapy. RESULTS:
      Eleven renal and one liver transplantation patient developed an abdominal
      malignancy. Among 11 renal transplantation patients eight were diagnosed as
      abdominal Kaposi's sarcoma (KS) and three as posttransplantation
      lymphoproliferative disorder (PTLD) upon spiral CT examination. In two patients
      the transplanted organ itself had malignant tumors: one patient had PTLD with
      Burkitt lymphoma in the transplanted liver and the other a renal cell carcinoma
      in the transplanted kidney. Abdominal PTLD and KS showed imaging findings and the
      site of organ involvement somewhat different from nontransplant patients. The
      most common pathologies in KS were liver lesions (n=6) and lymphadenopathy (n=6).
      But in abdominal PTLD, the spleen (n=3) was the most involved organ. CONCLUSIONS:
      The early diagnosis of abdominal malignancies after solid organ transplantation
      is crucial for the patient's prognosis, especially under immunosuppression. The
      abdominal spiral CT examination was an effective modality to depict a malignancy
      among patients with solid organ transplantation.

PMID- 17524894
TI  - Posttransplantation lymphoproliferative disorders in renal transplant recipients:
      report of over 20 years of experience.
AB  - INTRODUCTION: Despite the benefits of immunosuppressive medications to improve
      graft function, they have several adverse effects, such as development of
      neoplasms in renal transplant recipients. Posttransplantation lymphoproliferative
      disorders (PTLDs) are not uncommon complications, so we conducted a study to
      evaluate the characteristics of affected patients. METHODS: We enrolled 2117
      kidney recipients from June 1984 to March 2004 in order to find pathological and
      clinical evidence of neoplasms. We collected and analyzed all data on PTLD
      patients. RESULTS: Overall there were 46 recipients with different types of
      neoplasms, among which the most common types were diseases of the skin (24 cases,
      52.2%), Kaposi's sarcoma (15 cases, 32.6%), and PTLD (14 cases, 30.4%). The mean
      (+/- SD) age of PTLD patients at the time of transplantation was 37.86 +/- 9.67
      years and 42.8% were women. Median and mean (+/- SD) time interval to PTLD
      diagnosis were 38.5 and 50.35 +/- 41.7 months, respectively (range 1 to 146
      months). Types of PTLD in these patients were kidney lymphoma (14.3%);
      gastrointestinal (14.3%); brain lymphoma; tonsils; palatine; Hodgkin's lymphoma,
      large cell lymphoma, and acute lymphoblastic lymphoma (each 7.1%), with 28.6%
      unspecified types. The 1-, 5-, and 10-year patient survival rates after
      transplantation were 71.4%, 51.4%, and 44.3%, respectively. Despite discontinuing
      immunosuppressive therapy in PTLD patients, five of six surviving had graft
      function up to a mean time of 105.4 +/- 57.6 months after transplantation.
      CONCLUSION: Our findings showed that the prevalence of PTLD was 0.66%, which was
      less than reports from Western countries. The fact that there were surviving
      grafts for a considerable time despite discontinuing immunosuppressive therapy is
      of great importance.

PMID- 17524895
TI  - Anxiety and depression are correlated with higher morbidity after kidney
      transplantation.
AB  - BACKGROUND: Psychiatric comorbidities have been reported to be associated with
      low quality of life, but less attention has been paid to their impact on other
      morbidity measures. The aim of this study was to investigate the correlation of
      anxiety and depression with marital relation, sexual function, and sleep quality
      in kidney transplant recipients. METHODS: In a cross-sectional study between 2005
      and 2006, 88 kidney transplant recipients were divided into four groups according
      to their scores of anxiety and depression using Hospital Anxiety Depression Scale
      (HADS): group I(anx) (anxiety score <11; n=64); group II(anx) (anxiety score >or=
      11; n=24); group I(dep) (depression score <11; n=68); and group II(dep)
      (depression score >or= 11; n=20). Morbidity measures including quality of life
      (Short Form-36), marital adjustment (Revised Dyadic Adjustment Scale), sexual
      relationship (Relationship and Sexuality Scale), and quality of sleep (Pittsburgh
      Sleep Quality Index) were separately compared between groups of anxious versus
      nonanxious and depressed versus nondepressed. RESULTS: Group I(anx), compared
      with group II(anx), displayed a better state of mental health (48.80 +/- 7.14 vs.
      44.45 +/- 7.80; P=.01), general health (49.36 +/- 12.77 vs. 42.91 +/- 16.67;
      P=.05), marital adjustment (55.13 +/- 8.01 vs. 48.35 +/- 16.62; P=.04), and lower
      sleep disturbance (1.36 +/- 0.62 vs. 1.66 +/- 0.63; P=.05). Group I(dep),
      compared with group II(dep), showed lower fatigue score (39.79 +/- 8.30 vs. 46.84
      +/- 8.85; P=.002) and better sexual relationships (15.28 +/- 5.50 vs. 19.00 +/-
      5.92; P=.03). CONCLUSIONS: Screening for anxiety and depression in kidney
      transplant recipients is essential. Appropriate treatment of these prevalent
      psychiatric comorbidities may improve various aspects of patient well-being,
      including quality of life, sleep, marital relations, and sexual relationship.

PMID- 17524896
TI  - Are all domains of quality of life poor among elderly kidney recipients?
AB  - BACKGROUND: This study sought to answer whether all domains of HRQoL are low
      among elderly kidney recipients. METHODS: A cross-sectional study of 162 renal
      transplanted subjects included group I (age<40 years, n=85), group II (age
      between 40 and 55 years, n=55), and group III (age >55 years, n=22). We compared
      the total score of the Short Form health survey (SF-36) and its eight subscales,
      including physical functioning (PF), social functioning (SF), role limitations
      due to physical health problems (RPh), role limitations due to emotional problems
      (REm), mental health (MH), vitality (VT), bodily pain (BP), and general health
      perceptions (GH) between the study groups. RESULTS: As compared to groups II and
      I, group III, showed significantly lower scores of REm (49.12 +/- 23.22, 63.03 +/
      26.33, 64.36 +/- 26.54, P=.08), PF (48.94 +/- 27.41, 72.69 +/- 25.54, 72.14 +/-
      22.79, P=.001) and SF-36 total score (46.79 +/- 10.52, 54.77 +/- 10.66, 54.09 +/-
      9.35, P=.01). There were no significant differences among SF, RPh, MH, VT, and
      BP. Group III reported better GH than groups II and I (52.36 +/- 9.18, 48.71 +/-
      12.01, 43.50 +/- 14.81, P=.020). CONCLUSIONS: Increasing age did not result in
      poor health-related quality of life in all domains. The general health perception
      was better in the elderly, which might be due to their better coping ability.

PMID- 17524897
TI  - Anxiety and depression: a comparison between renal transplant recipients and
      hemodialysis patients.
AB  - BACKGROUND: Anxiety and depression are known causes of morbidity among patients
      with chronic illnesses. There is controversy whether hemodialysis or renal
      transplanted subjects have less severe anxiety or depression symptoms. We
      designed this study to evaluate these symptoms in the two groups of subjects.
      METHODS: In a case-control study performed in 2006, we randomly selected 32
      transplant recipients and 39 hemodialysis patients. The two groups were matched
      for gender, age, marital status, educational background, and somatic
      comorbidities. Symptoms of anxiety and depression were compared between the
      groups using the Hospital Anxiety Depression Scale. RESULTS: Anxiety score was
      significantly lower among transplant recipients compared with hemodialysis
      patients (8.61 +/- 3.09 vs 10.41 +/- 2.77; P=.01). There was no significant
      difference between the two groups in the score for depression (P>.05). In
      transplant recipients, the severity of anxiety was higher among those with a
      history of graft rejection and those <35 years at the time of transplantation
      (P<.05). The severity of depressive symptoms was higher among subjects with lower
      educational status (P<.05). CONCLUSION: Depressive symptoms did not seem to
      improve after renal transplantation, which highlights the need for screening and
      appropriate treatment of depression. Transplant recipients with a history of
      rejection or a young age at the time of transplantation should receive more
      attention for psychiatric problems.

PMID- 17524898
TI  - Marital quality in kidney transplant recipients: easy to predict, hard to
      neglect.
AB  - BACKGROUND: Given the significant role of post-renal transplant familial support
      in the patient's adherence to treatment, a study into the contributors to marital
      quality in this population seems necessary. This study sought to identify the
      predictors of poor post-renal transplant marital quality. METHODS: This cross
      sectional study was conducted in 2006 on 125 married kidney transplant
      recipients. Marital quality was evaluated using the Revised Marital Adjustment
      Scale (RMAS). A score below the fourth-quartile MAS score of a group of age- and
      sex- matched healthy controls was interpreted as poor marital relationship.
      Multiple logistic regression analysis was utilized to evaluate the predictors of
      poor marital relationship. RESULTS: The mean time interval between
      transplantation and assessment of marital quality was 43 +/- 15 months. Poor post
      renal transplant marital quality can be predicted by the kidney transplant
      recipient's sex (M/F) (odds ratio [OR]; 0.31; 95% confidence interval [CI], 0.11
      to 0.90; P=.031), age at transplantation (OR, 0.93; 95% CI, 0.89 to 0.98;
      P=.005), educational level (OR, 0.67; 95% CI, 0.44 to 1.03; P=.067), and monthly
      family income (OR, 2.20; 95% CI, 1.09 to 4.44; P=.028). CONCLUSION: Presenting a
      simple prediction model for poor post-renal transplant marital relationship, this
      study will make it possible to detect patients at a higher risk of poor marital
      quality and thus avoid treatment noncompliance. At the time of transplantation,
      using simple demographic variables and providing couple-based health education
      programs as a part of a familial approach to renal transplantation may improve
      the outcome of such high-risk patients.

PMID- 17524899
TI  - Outcome of living kidney transplant: pediatric in comparison to adults.
AB  - BACKGROUND: Renal transplantation is the most optimal way to manage children with
      end-stage renal disease. Despite its benefits, pediatric renal transplantation is
      a challenge for several transplantation centers in terms of achieving a
      satisfactory outcome. We sought to compare the long-term outcome of pediatric
      versus adult recipients who underwent renal transplantation. METHOD: We examined,
      2631 recipients of a first kidney from a living donor between 1982 and 2002. The
      two groups were matched for immunosuppressive therapy and number of HLA
      mismatches. The patients were divided into a pediatric (n=301; age <or= 18 years)
      and an adult group (n=2330; age > 18 years) to compare 5-year patient and graft
      survivals. RESULTS: The mean ages of the pediatric and adult groups were 40 +/-
      13 and 14 +/- 13 years, respectively. The 5-year graft survival was lower among
      the pediatric versus the adult group (56% vs 68%; P=.015) with no difference in
      patient survival (88% vs 86%; P>.05). CONCLUSION: The poorer graft survival in
      pediatric transplantation may be due to the nature of pediatric transplantation,
      in terms of inconsistent adherence to medication regimens, worse side effects of
      medications, higher rate of graft rejection due to recurrent disease, and more
      intense immunoreactivity of children.

PMID- 17524900
TI  - Does etiology of end-stage renal disease affect sleep quality in kidney
      transplant recipients?
AB  - BACKGROUND: That hypertension (HTN) as a leading cause of end-stage renal disease
      (ESRD) is linked to sleep disorders in the general population can be the basis of
      a hypothesis that HTN may be a contributing factor to the poor quality of sleep
      in some kidney transplant recipients. This study was designed to investigate the
      correlation between ESRD secondary to HTN and sleep quality among kidney
      transplant recipients. METHODS: In this case control study, 201 kidney transplant
      recipients were divided into group I (ESRD) secondary to HTN, (n=82) and group II
      (ESRD secondary to other causes, n=119). The groups were matched for medical
      comorbidities, demographic and clinical data, and symptoms of anxiety and
      depression. Sleep quality assessed by means of the Pittsburgh Sleep Quality Index
      (PSQI) was compared between the study groups. RESULTS: The mean (SD) of the total
      PSQI score was significantly high in group I compared with group II (7.42 +/-
      2.36 vs 6.60 +/- 3.07, P=.042). Similar results were observed for the sleep
      duration scores in the groups (1.22 +/- 1.12 vs 0.86 +/- 1.12, P=.026). In group
      I, all the other PSQI components were higher than those in group II, difference
      that were statistically significant. CONCLUSION: Sleep quality and duration was
      poorer among our kidney transplant recipients with ESRD secondary to HTN compared
      with the controls. Further studies, however, are required to investigate whether
      HTN is responsible for the reported poor quality of sleep in some kidney
      transplant recipients.

PMID- 17524901
TI  - Sleep quality and its correlates in renal transplant patients.
AB  - BACKGROUND: The aim of this study was to evaluate correlated morbidity measures
      with poor sleep quality among kidney transplanted patients. METHODS: In a cross
      sectional study of 125 Iranian kidney transplant patients in 2006, we employed
      self-administered questionnaires to evaluate the quality of sleep (PSQI), quality
      of life (SF-36), anxiety and depression, sexual activity, marital relationship,
      and medical comorbidity. Patients with PSQI score of >5 were considered to be
      "poor sleepers." Students t-test was used to compare the morbidity measures
      between the two groups: "poor sleeper" versus "good sleepers." RESULTS: Seventy
      eight (62%) patients were poor sleepers. This group showed a higher total medical
      comorbidity score (P=.009), more bodily pain, poorer general mental health, and
      less physical function on SF- 36 (P=.02), less sexual function, and more severe
      anxiety (P=.02). There was no significant difference between poor sleepers and
      good sleepers in the mean of other subscores of the SF-36, marital status, and
      depressive symptoms. CONCLUSIONS: A poor quality of sleep is common after kidney
      transplantation. This problem is associated with higher medical comorbidity and
      poorer emotional state. Therefore, more attention should be paid to evaluation of
      sleep quality in this patient population.

PMID- 17524902
TI  - Vascular complication and Doppler ultrasonographic finding after renal
      transplantation.
AB  - OBJECTIVES: Vascular complications are common after renal transplantation. In
      this study we correlated Doppler sonographic indices and transplant kidney
      function. METHODS: We reviewed data on 244 renal transplant patients. Doppler
      ultrasonographic evaluation was performed during the first 2 weeks after renal
      transplantation. We determined resistive index (RI) and pulsatility index (PI) in
      the interlobar arteries and thrombosis of renal and lower limb veins. Serum
      creatinine (Cr) and cyclosporine levels were evaluated prior to sonographic
      assessment. RESULTS: The mean age of the 142 male and 102 female patients was
      36.31 +/- 3.30 years. Prevalence of real artery stenosis was 9.5%. In these
      patients the mean serum Cr level (2.21 +/- 1.83 mg/dL) was significantly higher
      than among patients with patent renovascular tributary (1.49 +/- 1.00 mg/dL;
      P=.03). RI and PI were also significantly correlated with serum Cr(P=.05 and
      .001, respectively). There was no relationship between cyclosporine level or
      panel-reactive antibody with RI and PI. Retransplant patients showed higher RI
      than first renal allograft recipients (0.72 +/- 0.16 vs 0.63 +/- 0.11; P=.006).
      Serum Cr level was higher among renal allograft recipients with Doppler evidence
      of thrombosis of the lower limb veins (3.1 +/- 0.98 mg/dL versus 1.56 +/- 1.13
      mg/dL; P=.04). CONCLUSIONS: RI and PI are two valuable Doppler ultrasonographic
      markers to determine renal allograft function and related vascular complications.

PMID- 17524903
TI  - Duplex sonographic measurements in allografted kidneys: a cross-sectional study.
AB  - OBJECTIVES: The measurement of color Doppler sonography indices, such as
      resistive index (RI) and pulsatility index (PI), can help in the evaluation of an
      transplanted kidney. The aim of this study was to determine the correlation
      between Doppler sonography indices and demographic paraclinical findings in
      transplanted kidneys. METHODS: A cross-sectional study was performed on 47 (27
      male and 20 female) unrelated living renal transplanted patients. RESULTS: The
      mean age, body mass index (BMI), time since transplantation, pulse pressure index
      (PPI), intrarenal RI and PI were 38 +/- 13 years, 25 +/- 4.5, 48 +/- 31 months,
      0.34 +/- 0.06, 0.69 +/- 0.06, and 1.3 +/- 0.3, respectively. There were
      significant negative correlations between time since transplantation and
      intrarenal RI and PI (r=-.38, P<.01; r=-.4, P<.01, respectively). There was a
      significant correlation between patient age, creatinine clearance, and intrarenal
      RI (r=.30, P=.039; r=.3, P=.043, respectively). There were no significant
      correlations between intrarenal RI, PI, and BMI, cyclosporine trough level, PPI,
      recipient and donor sexes, and rejection episodes. Diabetic patients displayed
      higher RI (0.76 +/- 0.02 vs 0.68 +/- 0.06, P=.048) and patients with serum high
      density lipoprotein (HDL) level <40 mg/dL had higher PI than patients with HDL
      >or= 40 mg/dL (1.6 +/- 0.4 vs 1.2 +/- 0.3, P=.006). CONCLUSIONS: Intrarenal RIs
      did not decrease over a few years after transplantation. They can be a useful,
      feasible predictor of graft function. However, future multicenter trials should
      be performed to prove the predictive power of RI determination as a marker of
      renal function.

PMID- 17524904
TI  - Pelvic nerve neuropathy after kidney transplantation.
AB  - OBJECTIVES: We examined the relation of various age, gender, diabetes,
      hypertension, and graft function with the prevalence of femoral and lateral
      cutaneous nerves sensory and/or motor disturbances after kidney transplantation.
      MATERIALS AND METHODS: Among 129 patients who underwent kidney transplantation
      from April 2001 to March 2002. We excluded, 10 due to preoperative sensory
      disturbances. We evaluated the prevalence of sensory and/or motor disturbances
      preoperatively by physical examination and postoperatively by both physical and
      electromyography examinations. The clinical findings were correlated with the
      following risk factors: age, gender, preoperative dialysis duration, background
      diseases. (e.g., diabetes, hypertension), graft weight, nephron mass index,
      operative and retraction time, and rejection episodes. RESULTS: At 1 to 9 days
      postoperatively, 31 ng (26%) patients, suffered neuropathy of the lateral
      cutaneous nerve and 4 (3.3%), femoral neuropathy. No meaningful relation was
      detected between the incidence of neuropathy and these risk factors. The
      probability of neuropathy was greater among diabetics, hypertensives, women, and
      those with graft rejection episodes. All of these complaints were temporary.
      CONCLUSIONS: Post-kidney transplant femoral and/or lateral cutaneous nerve
      neuropathy is a prevalent complication particularly in diabetic, hypertensive,
      and female patients. Neuropathy is also more evident after graft rejection.

PMID- 17524905
TI  - Multidetector computed tomography angiography in detection of active bleeding in
      renal and liver transplant recipients.
AB  - OBJECTIVES: The aim of this study was to evaluate the effectivity of
      multidetector computed tomography angiography (MDCT-A) to detect active bleeding
      in transplant patients. MATERIALS AND METHODS: Between 1999 and 2006, 532
      patients underwent renal or liver transplantation. MDCT-A was performed on
      recipients who displayed decreased hemoglobin levels or who had a hematoma during
      abdominal ultrasound imaging. The MDCT-A used a 16-detector CT device (Siemens,
      Sensation) with slices 0.75 mm thick after injection of nonionic contrast media
      (4 mL per second). A multiple intensity projection (MIP) technique was used to
      maintain angiographic images in the axial and coronal planes. RESULTS: MDCT-A
      detected active bleeding among 23 posttransplant patients: 10 of arterial origin
      and 13 venous, as proven either by angiography or during operation. Among 8 of
      the 11 patients who underwent angiographic imaging the arterial origin was
      embolized. For three patients the angiographic evaluation was not helpful to find
      the bleeding point. A cohort of 5 of 12 patients did not undergo angiographic
      evaluation and were followed by clinical and ultrasonographic findings. Seven
      patients underwent re-operating. DISCUSSION: Management of the patients who were
      suspected to have active bleeding after renal or liver transplantation was
      benefitted by MDCT-A as an accurate and feasible screening modality.

PMID- 17524906
TI  - Outcome of renal allografts with multiple arteries.
AB  - BACKGROUND: Renal allograft transplantation with multiple arteries (MRA) was
      always avoided as much as possible as it is technically demanding and carries a
      higher MSK for complications. This was a single-center study to explore the graft
      outcomes of kidney transplantation with MRA. PATIENTS AND METHODS: We
      retrospectively reviewed the medical records of 35 patients who received kidney
      grafts with MRA for the surgical technique, surgical complications, graft
      function, and graft survival. The results were compared with those achieved in
      recipients of kidney grafts with a single renal artery (SRA). RESULTS: Of 35
      grafts, there were 2 renal arteries in 30 grafts, and 3 renal arteries in 5
      grafts. In the MRA group, there were 7 instances of surgical complications, the
      mean serum creatinine levels were 122, 139, and 156 micromol/L at 1 month, 1
      year, and 5 years, respectively, and the actuarial graft survival rates were
      94.3%, 88.6%, and 83% at 1, 5, and 10 years, respectively. In the SRA group,
      there were 56 instances of surgical complications, the mean serum creatinine
      levels were 115, 121, and 141 micromol/L at 1 month, 1 year, and 5 years,
      respectively, and the actuarial graft survival rates were 93.7%, 88.1%, and 84.4%
      at 1, 5, and 10 years, respectively. CONCLUSION: Although transplantation of MRA
      grafts might carry a relatively higher risk for complications, it is justified
      because it gives results comparable with those achieved in SRA.

PMID- 17524907
TI  - Dual kidney transplantation using midline extraperitoneal approach: description
      of a technique.
AB  - Dual kidney transplantation is performed using organs from marginal donors that
      are considered unsuitable for single kidney transplantation. In this report, we
      describe a simple technique of transplanting these organs extraperitoneally
      through a lower midline incision.

PMID- 17524908
TI  - Renal allograft venous thrombosis is salvageable.
AB  - BACKGROUND: Renal vein thrombosis (RVT) is an uncommon but serious complication.
      It usually occurs early after surgery. While compression of the renal vein is the
      most common cause, early rejection and hemostatic defects are other known causes.
      The symptoms are nonspecific and diagnosis is often delayed. Ultrasonography and
      renal isotope scan findings may resemble acute rejection or acute tubular
      necrosis. PATIENTS AND METHODS: We retrospectively reviewed the records of 684
      recipients who were transplated between November 1993 and May 2006. The diagnosis
      of RVT was suspected by an unexplained drop in urine output, rise in serum
      creatinine, or hematuria, and confirmed by Doppler ultrasound and isotope
      scanning. Urgent exploration was performed in all suspected cases. RESULTS: Seven
      incidences of biopsy-proven RVT were encountered, including 3 associated with
      hematoma and 1 with rejection. Four grafts were from cadaveric donors. Three
      grafts were salvaged. CONCLUSIONS: The incidence of RVT in the present series was
      1%. All cases developed in the first 2 weeks after transplantation. It was more
      common in adults, in female recipients, and in cadaveric grafts. Early diagnosis
      and intervention were the keys to salvage.

PMID- 17524909
TI  - Severity of chronic pain affects health care utilization after kidney
      transplantation.
AB  - BACKGROUND: While the association between chronic pain and high health care
      utilization is a known issue in the general population, this relation has not
      been well studied among kidney transplantation patients. METHODS: The subjects
      were first-time kidney transplant recipients engrafted between 2003 and 2006 and
      6 months to 5 years postoperatively. Using SF-36 Bodily Pain Scale, patients were
      categorized in three groups: group I, those with scores over 66.6; group II,
      between 66.6 and 33.3; and group III, over 33.3. The subjects' health care
      utilization was prospectively assessed by recording the number of hospital
      admission days and the frequency of home nurse visits, outpatient physician
      visits, and emergency department visits for any medical reason in a 6-month
      period. RESULTS: A stepwise increase in the frequency of patients admitted to the
      hospital (P=.017), and those referred to emergency departments (P=.007) was
      correlated with greater severity of pain in the three groups. However, the
      frequency of patients having outpatient physician visits (P=.30) or home nurse
      visits (P=.387) did not vary significantly. Similarly, with increased pain
      severity, an increase was observed in the number of emergency department visits
      (P=.005) and duration of hospital stays (P=.049), but not in the number of home
      nurse (P=.890) or physician visits (P=.112). CONCLUSION: The severity of pain
      seems to increase the amount of health care use among kidney transplant patients.
      To minimize associated costs, appropriate pain rehabilitation programs are
      suggested.

PMID- 17524910
TI  - Pain affects health-related quality of life in kidney transplant recipients.
AB  - BACKGROUND: Chronic pain is prevalent in end-stage renal disease patients
      undergoing chronic hemodialysis. We do not fully know the intensity of chronic
      pain experienced by kidney recipients in comparison to those on chronic
      hemodialysis and healthy controls. Moreover, the effect of chronic pain on kidney
      recipients' health-related quality of life (HRQoL) is yet to be comprehensively
      addressed. We designed this study to find an answer to these questions. METHODS:
      In this case control study, we studied 205 kidney recipients, 69 hemodialysis
      patients, and 100 healthy controls, who were matched for age, sex, monthly family
      income, and educational level. The patients were evaluated for the intensity of
      chronic pain by Visual Analogue Scale (VAS). HRQoL was measured with Short Form
      36 (SF-36) in the kidney recipients. Chronic pain intensity was compared in the
      study groups, and in the kidney recipients the correlation between SF-36
      subscores and severity of pain was assessed. RESULTS: Severity of pain in the
      kidney recipients was lower than the hemodialysis patients, but more than the
      healthy controls (P=.001). The VAS pain score negatively correlated with the
      scores of SF- 36 total (r=-.329, P=01), mental health (r=-.190, P=07), physical
      health (r=-.275, P=.001), physical function (r=-.339, P=.001), role limitation
      due to physical problems (r=-.478, P=.001), role limitation due to emotional
      problems (r=-.326, P=.001), and bodily pain (r=-.894, P=.001). DISCUSSION: The
      intensity of chronic pain experienced by the kidney recipients is less than that
      experienced by patients under chronic hemodialysis, but higher than healthy
      subjects. Focusing on chronic pain as a cause of post-renal transplantation
      morbidity is expected to improve post-renal transplantation quality of life.

PMID- 17524911
TI  - Pustular psoriasis after renal transplantation.
AB  - Cutaneous manifestations in renal transplant recipients are frequently
      represented by infections and cancerous lesions. However, dermatologic lesions
      secondary to autoimmune diseases are rare. We report a case of pustular psoriasis
      occurring after renal transplantation in a 31-year-old woman with a history of
      vitiligo. The patient was on hemodialysis for 2 years for undetermined chronic
      nephropathy. She received an HLA identical live related transplant from her
      brother. She was maintained on an immunosuppressive regimen of corticosteroids,
      azathioprine, and cyclosporine, which was replaced with mycophenolate mofetil
      because of neurotoxicity and azathioprine was stopped. Thirty-one months after
      renal transplantation, she developed pustular psoriasis which was treated with
      retinoids; she experienced a relapse and resistance to treatment despite the
      reintroduction of cyclosporine.

PMID- 17524912
TI  - Evaluation of effect of renal transplantation in treatment of restless legs
      syndrome.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a common cause of sleep disturbance
      frequently experienced by hemodialysis patients. It is a neurological movement
      disorder. Patients with RLS suffer an irresistible urge to move the legs during
      inactivity with relief by motion and various activities. MATERIALS AND METHODS:
      We investigated the clinical course of RLS in 30 (12 female and 18 male)
      hemodialysis patients with mean dialysis duration of 16.8 +/- 14.13 months who
      underwent kidney transplantation. Patients were given a standardized
      questionnaire evaluating details of RLS at baseline and twice after kidney
      transplantation. They were diagnosed to have RLS by International RLS Study Group
      criteria. Biochemical (serum calcium, phosphate, Na, and K and blood urea and
      creatinine) and hematological indices (serum iron, hemoglobin) were measured at
      each time. RESULTS: RLS in hemodialysis patients was significantly reduced by
      renal transplantation (43.3%; P<.0001). There was a significant association
      between RLS and lower serum iron (P<.01) and phosphorus (P<.02) after renal
      transplantation: We did not observe any association between hemoglobin levels,
      age, sex, dialysis duration, and time after transplantation with RLS. CONCLUSION:
      Kidney transplantation showed a strong, positive influence on RLS symptoms in
      hemodialysis patients. Correction of serum phosphate and serum iron (by
      mechanisms different than its effect on hemoglobin) can affect RLS in kidney
      transplant patients.

PMID- 17524913
TI  - An ophthalmological complication: central serous chorioretinopathy in a renal
      transplant recipient.
AB  - BACKGROUND AND OBJECTIVE: Ophthalmological complications in transplanted
      recipients often due to underlying disorders or drug use consist of anterior
      segment and posterior segment complications. Among the posterior complications,
      Central serous chorioretinopathy (CSCR) is related to high-dose steroids, stress,
      or cyclosporine and usually has a good outcome. The aim of this study was to
      report a case of CSCR as an ophthalmologic complication of renal transplantation.
      CASE REPORT: A 36-year-old man hospitalized for the treatment of rejection
      suffered severe visual loss in both eyes. After examination and fluoresein
      angiography, we diagnosed CSCR due to high-dose steroid therapy for rejection.
      With tapering of the drug and after about 3 months, visual acuity became normal.
      CONCLUSION: Visual acuity changes must be followed up carefully in all transplant
      recipients, but CSCR usually has a good prognosis. If it does not improve,
      retinal laser therapy is needed.

PMID- 17524914
TI  - Impact of pregnancy on the outcome of kidney transplantation.
AB  - BACKGROUND: There is still controversy over whether pregnancy adversely affects
      renal transplantation outcomes. We, thus, compared two groups of kidney
      transplant recipients in terms of patient survival and allograft function: those
      who did versus did not conceive posttransplant. METHODS: This historical cohort
      study conducted between 1996 and 2002, divided female kidney transplant
      recipients of reproductive age into group I (n=86, at least one posttransplant
      pregnancy) and group II (n=125, no posttransplant pregnancy). The two groups were
      matched for age, cause of end-stage renal disease (ESRD), treatment protocol, and
      first creatinine (Cr). All patients received a first transplant and all had a Cr
      less than 1.5 mg/dL on entry into the study. The subjects were followed for 45.4
      +/- 22.0 and 46.3 +/- 19.8 months, respectively (P>.05). Five-year patient and
      graft survivals and Cr were considered to be the main outcome measures. RESULTS:
      Mean (SD) age in groups I and II was 26.6 +/- 6.6 and 26.9 +/- 8.1 years,
      respectively (P>.05). Five-year patient and graft survival rates were not
      significantly different between the study groups. Of the women in group 1, only 9
      (10.5%) subjects displayed elevated serum Cr levels (>1.5 mg/dL) at the end of
      follow-up, while the serum Cr levels in 35 (28%) group II patients were above 1.5
      mg/dL (P=.024). CONCLUSION: Our results indicates pregnancy did not seem to
      adversely affect patient and graft survival among kidney transplant recipients.
      Renal transplantation in stable women of childbearing age should not be a
      contraindication to pregnancy.

PMID- 17524915
TI  - Black tea improves endothelial function in renal transplant recipients.
AB  - BACKGROUND: Endothelial damage and dysfunction are commonplace in renal
      transplant recipients. Impaired endothelial function is an important contributor
      to cardiovascular diseases. We hypothesized that short-term black tea consumption
      may improve endothelium-dependent arterial dilation in kidney recipients.
      METHODS: Fifteen recipients were studied on an outpatient basis in a single,
      university-affiliated clinic. Inclusion criteria were stable and good allograft
      function. The main exclusion criteria were uncontrolled hypertension, smoking,
      alcohol consumption, coffee drinking, diabetes mellitus, and coronary artery
      disease, or a history of upper limb vascular manipulations. After overnight
      fasting, the brachial artery diameter (BAD) was measured at the end of diastole
      using an ultrasound machine before (basal BAD) and 1 minute after temporary (
      approximately 3 minutes) external occlusion (posthyperemia BAD). Flow-mediated
      vasodilation (FMV) and percent of FMV (FMV%) were calculated by appropriate
      formula. FMV and FMV% were determined at baseline and 2 hours after consuming 0.5
      L freshly brewed black tea. For control, the study was repeated for each patient
      the next day and FMV and FMV% were determined before and 2 hours after consuming
      0.5 L of water. RESULTS: The men age of patients was 37.2 +/- 9.7 years (range,
      25 to 50) with a male:female ratio of 3:2. Patients were 26.8 +/- 10.6 months
      postrenal transplantation. Black tea consumption significantly increased
      posthyperemia BAD, FMV, and FMV% (P<.05). However, water consumption did not
      alter the basal or posthyperemia BAD, FMV, or FMV% (P>.05). CONCLUSION: Based on
      our study, short-term consumption of black tea may improve endothelial function
      and endothelium-dependent arterial vasodilation in renal transplant recipients.

PMID- 17524916
TI  - Right lobe adult living-donor liver transplantation.
AB  - Living-donor liver transplantation is another treatment option to cadaveric liver
      transplantation in adult recipients. We report the outcomes of 49 right lobe
      adult living-donor liver transplantations performed at our institution between
      April 2003 and June 2006. The mean age of the recipients was 41.7 +/- 12.5 years.
      The median graft-to-recipient weight ratio was 1.2% +/- 0.4%. In recipients, the
      mean operative time was 10.6 +/- 2.7 hours. The mean number of blood transfusions
      administered was 4.1 +/- 5.1 units. The mean time spent in the intensive care
      unit was 2.3 +/- 1.5 days. In recipients, five vascular and five biliary
      complications occurred during the early postoperative period, and four vascular
      and two biliary complications developed in the late postoperative period.
      Thirteen of the 49 recipients died within 4 months of surgery. The mean age of
      the donors was 36.6 +/- 9 years. In the donors, the mean operative time was 6.4
      +/- 1.6 hours, mean residual liver volume was 43.3% +/- 6.1%, and the mean
      hospital stay was 9.5 +/- 4.5 days. Two donors required an intraoperative blood
      transfusion. None of our donors died, but six complications occurred in four
      donors. The mean postoperative follow-up was 13.4 +/- 9.6 months. In conclusion,
      in Turkey, as in other countries, organ demand exceeds organ availability. Graft
      size presents a problem for adult recipients, but right lobe living donor
      transplant may be a life-saving option for these recipients when performed by
      experienced surgical teams.

PMID- 17524917
TI  - Living-donor liver transplantation: results of a single center.
AB  - In the absence of cadaveric donor liver transplantation, living-donor liver
      transplantation (LDLT) is an alternative option for patients with end-stage liver
      disease. The objective of this study was to evaluate the outcome of LDLT at a
      single medical center in Turkey. We retrospectively analyzed the results of 101
      LDLTs in 99 recipients with end-stage liver disease. We transplanted 49 right
      liver lobes, 16 left lobes, and 36 hepatic segments II and III. Most donors (46%)
      were parents of the recipients. Seventeen recipients had concomitant
      hepatocellular carcinoma and cirrhosis. Retransplantation was performed in two
      recipients. Ten hepatic arterial thromboses, 1 hepatic arterial bleeding, and 12
      biliary leaks occurred in the early postoperative period. Most complications were
      treated with interventional techniques. Three hepatic vein stenoses, three portal
      vein stenoses, one hepatic arterial stenosis, and six biliary stenoses developed
      during the late postoperative period. Recipients with those complications were
      treated with interventional techniques. Mean follow-up was 14.2 +/- 10.9 months.
      During that time, no tumor recurrence was detected in any recipient with
      hepatocellular carcinoma. Twenty-two recipients died during the follow-up. At
      this time, the remaining 77 recipients (77%) are alive, exhibiting good graft
      function. In general, complication rates are slightly higher after LDLT than
      after cadaveric liver transplantation. However, most complications can be treated
      with interventional techniques. LDLT continues to be a life-saving option in
      countries without satisfactory cadaveric donation rates.

PMID- 17524918
TI  - Liver transplantation for small babies.
AB  - Orthotopic liver transplantation remains a major medical and surgical challenge
      in small pediatric patients. From April 2003 to June 2006, 21 small babies (each
      of whom weighed less than 10 kg or was younger than 1 year of age) underwent
      orthotopic liver transplantation. Five were girls and 16 were boys with a mean
      age of 15.7 +/- 9.3 months (range, 2-24 months); their mean weight at the time of
      transplantation was 9.8 +/- 3.6 kg (range, 6-16 kg). All transplants were
      obtained from a living-related donor. Left lateral segment was used for all
      transplantations. The median graft-to-recipient weight ratio was 3.5% +/- 1.2%
      (range, 1.5%-6.1%). During the early postoperative period, hepatic arterial
      thrombosis was identified in 4 patients, and a biliary leak was detected in 2
      patients. In 2 patients, portal vein stenosis was identified during the late
      postoperative period. At the time of this writing, the 17 alive patients (81%)
      exhibited good graft function at median follow-up of 14.8 +/- 10.9 months (range,
      1-39 months). Four patients died during the follow-up. Histological examination
      revealed hepatocellular carcinoma in 2 patients, and Burkitt's lymphoma in 1
      patient. In conclusion, our data confirmed that living-related donors, especially
      in this age group, provide a reliable source for the organ pool. Satisfactory
      results can be achieved despite the anatomic handicaps of this age group.

PMID- 17524919
TI  - Pediatric liver transplantation for acute liver failure.
AB  - The only proven therapy for patients unlikely to recover from acute liver failure
      (ALF) is liver transplantation. Correct diagnosis of these individuals and rapid
      referral to a transplant center are crucial. We evaluated 12 pediatric patients
      with ALF who underwent liver transplantation (LT) at our institution during a 3
      year period. The reasons for transplantation were hepatitis A (3 patients); non
      A, non-E hepatitis (3); autoimmune hepatitis (1); fulminant Wilson's disease (3);
      Amanita phalloides (mushroom) poisoning (1); and hepatitis B and toxic hepatitis
      with leflunomide treatment (1). Seven of the participants were female and five
      were male (mean age, 9.1 +/- 4.2 years). Three received right liver-lobe grafts,
      one received a whole liver graft, and the remainder received left or left-lateral
      liver lobe grafts. All patients recovered from hepatic coma the second
      postoperative day. Two patients died at postoperative days 57 and 71 due to adult
      respiratory distress syndrome and sepsis with multiorgan failure, respectively.
      One patient required retransplantation because of chronic rejection 7 months
      after the initial transplantation. That patient died 10 days after
      retransplantation because of sepsis. Nine patients were healthy at follow-up
      (range, 2-46 months). LT is the only treatment option for ALF in patients in
      countries with low organ-donation rates. In this scenario, donor preparation in a
      limited time frame is difficult. We have been able to decrease the duration of
      donor preparation to approximately 4 hours (including biopsy of the donated liver
      tissue).

PMID- 17524920
TI  - Duct-to-duct biliary reconstruction in pediatric liver transplantation: one
      center's results.
AB  - In pediatric liver transplantation, both for cadaveric and living-related
      patients, the Roux-en-Y hepaticojejunostomy is often preferable to biliary
      reconstruction. Duct-to-duct biliary reconstruction in pediatric patients has
      been utilized only in a limited numbers of studies. Here, we retrospectively
      review our experience with duct-to-duct biliary reconstruction in pediatric liver
      transplantation patients. Since September 2001, 46 liver transplantations have
      been performed in 44 patients (29 boys and 15 girls of mean age, 8.4 +/- 5.5
      years). For the anastomoses, a corner-saving suture technique was used with 6-0
      or 7-0 polypropylene monofilament nonabsorbable suture. A T tube was used in
      three patients, and in 11 patients, a straight feeding tube was inserted from the
      recipient common bile duct to the anastomotic site. A transhepatic biliary
      catheter insertion technique was used in 28 patients for external bile drainage;
      the remaining four patients had no tubes or stents. Four patients developed bile
      leakage in the early postoperative period. Three of these patients were treated
      with percutaneous drainage with excellent outcomes; the remaining patient
      required reoperation with a Roux-en-Y hepaticojejunostomy for bile leakage. Four
      biliary stenoses occurred in the late postoperative period. All biliary stenoses
      were successfully treated with balloon dilatation. There was no mortality or
      graft loss due to biliary complications. Of the 44 original patients, 36 (82%)
      are well at this time, with optimal liver function during follow-up (2-34
      months). The remaining eight (18%) died during the study from acute respiratory
      distress syndrome (n=2), sepsis with multiorgan failure (n=5), and intracranial
      bleeding (n=1). Our results showed that duct-to-duct biliary reconstruction is a
      safe and easy technique for pediatric patients.

PMID- 17524921
TI  - Higher graft-to-host ratio may decrease posttransplant mortality in patients with
      a high MELD score.
AB  - The aim of this study was to determine whether scores from the model for end
      stage liver disease (MELD) can be used in the preoperative strategic planning of
      transplantation surgery. We retrospectively analyzed the outcomes of 62 adult
      liver transplantation patients whose operation was performed at our center
      between January 2001 and June 2006. All patients had MELD scores between 8 and 35
      with an average value of 20. We compared postoperative mortality among patients
      who had MELD scores higher than 20 as determined by their graft-to-host ratios.
      We separately grouped the patients whose graft-to-body weight ratio (GBWR) was
      equal to or lower than 1 and whose GBWR was higher than 1. The GBWRs associated
      with mortality after living-donor liver transplantation in the early
      postoperative period were considered significant (P=.005). MELD scores were also
      found to be associated with mortality (P=.006). Mortality rates in patients with
      high MELD scores and a low GBWR were highest among the other combinations. In
      conclusion, we found that GBWR lower than 1 and MELD score higher than 20 are
      significant risk factors for mortality after living donor liver transplantation.
      Patients with low MELD scores can undergo transplantation when their GBWR is
      lower than 1, but recipients with high MELD scores should receive grafts only
      when their GBWR is higher than 1.

PMID- 17524922
TI  - Liver transplantation for autoimmune hepatitis: a single-center experience.
AB  - OBJECTIVE: To present our experience with deceased donor liver transplantation
      (DDLT) and living-donor liver transplantation (LDLT) for autoimmune hepatitis
      (AIH). PATIENTS AND METHOD: Between April 2001 and November 2006, a total of 116
      LT procedures were performed (73 DDLTs and 43 LDLTs) in 112 patients (4
      retransplants). Of the 112 recipients, 16 patients (14.3%) were transplanted for
      AIH (15 DDLTs and 1 LDLT). All recipients received FK506- and steroid-based
      immunosuppressive regimens. RESULTS: The male/female ratio was 3/13, median age
      was 22 years (range, 15 to 35), and the median MELD score was 25 (range, 11 to
      40). Arterial reconstruction was needed in four DDLTs due to severe steroid
      induced angiopathy. After a median follow-up period of 530 days (range, 11 to
      2016), the overall patient and graft survival rates were 93.8%. Only one patient
      died following LDLT due to primary graft nonfunction. Histopathologic recurrence
      was seen in three patients (18.7%) and was successfully treated by optimizing
      immunosuppression. Markedly elevated serum CA19-9 levels (median, 1069; range,
      217 to 2855) was seen in four patients (28%), malignancy was ruled out and all
      patients normalized serum CA19-9 levels within the first 3 months posttransplant.
      Steroids withdrawal failed in all recipients and was always accompanied with
      almost immediate elevation of liver enzymes. CONCLUSIONS: In our experience, LT
      for AIH shows excellent long-term outcomes, patients are usually young women who
      present with acute deterioration and high MELD scores, and usually require long
      term steroids to prevent rejection and disease recurrence. Some patients have
      markedly high CA19-9 in absence of malignancy. Some patients also have severe
      steroid-induced hepatic artery angiopathy necessitating arterial reconstruction
      during the transplant surgery.

PMID- 17524923
TI  - Expanded criteria for hepatocellular carcinoma and liver transplantation.
AB  - In this study, we evaluated our early results of liver transplantation for
      hepatocellular carcinoma (HCC). Between January 2004 and June 2006, 26 patients
      (4 females, 22 males; aged 1.1-65 years) with preoperatively diagnosed or
      incidental HCC underwent liver transplantation at our center. Inclusion criteria
      (independent of tumor size and number of tumor nodules) were no invasion of major
      vascular structures and no evidence of extrahepatic disease. In 13 of the
      patients, tumors were beyond the Milan criteria. At this writing, at a mean
      follow-up of 16.5 months (range, 1-31 months), all patients were doing well with
      excellent graft function. The longest survival is 2.5 years, and our patient
      survival rate is 100%. There has been only 1 tumor recurrence, which occurred 4
      months after liver transplantation. In conclusion, liver transplantation provides
      long patient and disease-free survival, even in patients with HCC that exceeds
      the Milan criteria.

PMID- 17524924
TI  - Computed tomography volumetric follow-up of graft volume in living related liver
      recipients.
AB  - AIM: Liver regeneration is a fascinating process that makes living related donor
      transplantation feasible for patients. In this study we evaluated the changes in
      graft volumes among living related liver transplantation (LRLT) patients using
      computerized tomography (CT)-assisted volumetry technique. MATERIALS AND METHODS:
      Thirty three patients (17 adults, 16 children) who underwent liver
      transplantation were included in this study. Pediatric patients were referred to
      as group A, and adult patients were referred to as group B. The initial graft
      weight measured during operation was used as the initial graft volume. All
      patients' graft volumes were retrospectively calculated by CT volumetry
      technique. The data was compared with the initial graft volume in each patient.
      Paired samples Student t test was used for statistical analyses. RESULTS: The
      graft volume increased from 2.7% to 285.6% with the mean increase 78% in group A,
      and 10.5% to 150.8% with a mean increase of 89% in group B. These changes were
      significant (P<.0001) in both groups. DISCUSSION: The liver regeneration of
      recipient grafts is more complicated than that of the donors. There are a limited
      number of reports of complete volume recovery. We observed significant volume
      regeneration in liver grafts after transplantation, which was easily followed by
      CT-assisted volumetry.

PMID- 17524925
TI  - Multidetector computed tomographic angiography findings of splenic artery steal
      syndrome in liver transplantation.
AB  - AIMS: Splenic artery steal syndrome, a common complication in liver
      transplantation, is diagnosed by conventional angiography showing an enlarged
      splenic artery and by dynamic findings. The aim of this study was to determine
      multidetector computed tomographic angiography (MDCTA) findings of splenic artery
      steal syndrome to develop diagnostic criteria. MATERIALS AND METHODS: Ten
      patients were diagnosed as displaying splenic artery steal syndrome among 198
      liver transplant patients. The diagnosis was confirmed by celiac angiography. In
      eight of them, MDCTA was performed. Axial and coronal maximum-intensity
      projection images were obtained in arterial and portal phases. We measured the
      diameter of the celiac trunk and of the splenic, left gastric, common hepatic,
      superior mesenteric artery, and transplant hepatic arteries. We also measured the
      diameter of the proximal and the distal segments of the abdominal aorta, along
      with the size of the spleen, the ratio of the splenic artery to the common
      hepatic artery, the ratio of splenic artery to transplant hepatic artery, the
      diameter of portal vein and superior mesenteric vein. The control group consisted
      of liver transplant patients with normal liver enzyme levels. We performed
      Student t test for statistical examination. RESULTS: The diameter of the splenic
      artery (P<.05), the size of the spleen (P<.01), and the ratio of the splenic to
      the transplant hepatic arteries (P<.05) was significant between the two groups.
      The diameter of the splenic artery was larger than 4 mm in all patients in the
      study group. CONCLUSIONS: Conventional angiography was mandatory for the
      diagnosis of splenic artery steal syndrome. MDCTA is a noninvasive method. Some
      computed tomography criteria are important for early diagnosis and treatment.

PMID- 17524926
TI  - Does donor's fatty liver change impact on early mortality and outcome of liver
      transplantation.
AB  - BACKGROUND: The effect of donor fatty liver on graft survival is still uncertain.
      The aim of this study was to determine the influence of steatosis on the outcomes
      of OLT among our recipients. METHODS: In this retrospective study, we evaluated
      the effect of donor liver steatosis on postoperative liver function and
      prognosis. Data obtained from liver transplantation data registry of our organ
      transplant center. Liver biopsies taken before transplantation were reviewed by
      two pathologists. Pathology reports were divided into four groups: normal
      pathology; mild fatty change (10%-30%); moderate (30%-60%); and severe steatosis
      (>60%). Livers with severe steatosis were excluded from transplantation. Factors
      determining transplantation outcome, such as early mortality, duration of
      intensive care unit (ICU) and hospital stay, clinical rejection episodes, and
      graft surgical complications, were compared between subjects who received donor
      liver, with various degrees of steatosis. RESULTS: Three-month survival rates in
      recipients without donor liver fatty change, subjects with mild fatty change (10%
      30%) and those with moderate (30%-60%) steatosis were 68%, 72%, and 76%,
      respectively, which were not significantly different (P>.05). Furthermore, short
      term (hospital) mortality (20%, 14.3%, and 21.2%), hospital stay (30.89, 29.93,
      and 23.62 days), and length of ICU admission (5.06, 5.89, and 4.39 days) were not
      significantly different. In addition, Child score of recipients, pre- and
      postoperative liver function enzyme changes were similar. CONCLUSION: Mild-to
      moderate (up to 60%) liver fatty change was not found to be associated with a
      worse prognosis in OLT.

PMID- 17524927
TI  - Intraoperative transhepatic biliary catheter insertion technique for biliary
      reconstruction: early results.
AB  - Biliary complications are critical problems in liver transplantation. Herein, we
      retrospectively analyzed the early results of an intraoperative transhepatic
      biliary catheter insertion technique for biliary reconstruction. Since November
      2004, we have used this technique in 66 patients (32 children and 34 adults). In
      the new technique, a 5- F Kumpe catheter is inserted into the biliary system in 2
      steps. One step is completed at the back table; the second step is completed
      during the recipient operation. Fourteen patients received whole-liver grafts, 25
      received a right lobe, and 27 received a left-lateral or a left lobe. The mean
      graft weight-to-body weight ratio in the living-donor liver transplantations was
      1.6% +/- 1.0% (range, 0.8%-4.1%). Intraoperative transhepatic biliary catheter
      insertion was performed with a duct-to-duct anastomosis in 60 patients and with a
      Roux-en-Y hepaticojejunostomy in 6 patients. Five biliary complications occurred
      in 4 patients. Two of these 4 patients had bile leakage from the anastomotic site
      during the early postoperative period. Biliary stenoses developed at the
      anastomotic site in 2 patients and from a nonanastomotic site in 1 patient in the
      late postoperative period. In conclusion, this new technique of biliary
      reconstruction with intraoperative biliary catheter insertion has significantly
      reduced our complication rate. Transhepatic biliary stenting seems to prevent
      biliary complications and makes it simple to maintain percutaneous access in the
      event that problems arise. Intraoperative transhepatic biliary catheter insertion
      at the back table is a safe means of providing good biliary drainage after liver
      transplantation.

PMID- 17524928
TI  - Predictors of immediate tracheal extubation in the operating room after liver
      transplantation.
AB  - Immediate postoperative extubation may reduce the incidence of postoperative
      respiratory complications after orthotopic liver transplantation (OLT). We
      evaluated the predictors of immediate tracheal extubation in the operating room
      (OR) in our patients by retrospectively reviewing data from all patients who
      underwent OLT between January 2004 and June 2006. The patients were divided into
      two groups according to whether they had undergone extubation in the OR (group 1
      n=52) or in the intensive care unit (ICU; group 2 n=48). When compared with the
      patients in group 2, those in group 1 had lower mean preoperative serum
      creatinine levels (0.9 +/- 1 vs 0.6 +/- 0.3 mg/dL, P=.04) and intraoperative
      transfusion requirements (packed red blood cells, 35.5 +/- 29.8 vs 25.6 +/- 19.0
      mL/kg; P=.05, and fresh frozen plasma, 33.1 +/- 15.6 vs 25.7 +/- 14.3 mL/kg;
      P=.01). The incidence of intraoperative hypotension and emergent OLT was
      significantly greater in group 2 than group 1 (33.3% vs 13.5%, P=.01 and 45.8% vs
      21.2%, respectively, P=.009). On logistic regression analysis, only emergent OLT
      (P=.009, odds ratio = 3.5) and intraoperative hypotension (P=.018, odds ratio =
      3.7) were significantly associated with a lower probability of immediate
      postoperative extubation in the OR. Our results suggested that hemodynamic
      stability and elective OLT were predictors of successful immediate tracheal
      extubation in the OR.

PMID- 17524929
TI  - Dermatologic complications after liver transplantation: a single-center
      experience.
AB  - OBJECTIVE: To report our experience with dermatological complications after both
      deceased donor liver transplantation (DDLT) and living-donor liver
      transplantation (LDLT). PATIENTS AND METHODS: Between April 2001 and November
      2006, a total of 116 liver transplantation (LT) procedures were performed (73
      DDLTs and 43 LDLTs) in 112 patients (4 re-transplants). Posttransplant
      dermatological problems were recorded. RESULTS: Among 112 OLT recipients, 14
      patients (12.5%) experienced dermatologic problems: epidermolysis bullosa
      acquisita in one patient, which was self-limiting; graft-versus-host-disease in
      one patient treated with high-dose steroids; Kaposi sarcoma in one patient
      treated with surgical excision and conversion to sirolimus-based
      immunosuppression; drug-induced cutaneous vasculitis with deep thigh ulcer
      formation treated by drug discontinuation and surgical excision of the ulcer;
      herpes zoster in one patient treated with intravenous antiviral therapy; herpes
      simplex in two patients treated with local antiviral cream; cyclosporine-induced
      gingival hyperplasia treated with conversion to FK506; cyclosporine-induced
      hypertrichosis treated with conversion to FK506; steroid-induced skin
      hyperpigmentation in one patient treated with steroid withdrawal; hypomagnesemia
      induced hair loss treated with daily oral magnesium supplement; pressure-induced
      alopecia areata in two patients that was self-limiting; and finally, one patient
      with a pressure-induced heel ulcer that was treated conservatively. In 8 of 14
      patients (57%) who suffered from dermatologic problems, the complication was
      primarily related to immunosuppressive drugs. CONCLUSIONS: In our experience,
      dermatologic complications following LT are not uncommon and usually related to
      immunosuppressive therapy. Most complications could be prevented by optimizing
      immunosuppression. The majority of complications were easily managed by simple
      adjustment of immunosuppression.

PMID- 17524930
TI  - Early hepatic artery thrombosis after liver transplantation: diagnosis and
      treatment.
AB  - BACKGROUND: Hepatic artery thrombosis (HAT) occurs in 3% to 9% of all liver
      transplantations with acute graft failure as a possible sequel. METHODS: Eleven
      episodes of HAT were identified among 256 orthotropic liver transplantations
      (whole, LDCT, split) performed on 253 patients between April 1993 and July 2006.
      HAT was suspected clinically and confirmed by Doppler ultrasonography, magnetic
      resonance angiography, angiography, or reexploration. One patient was excluded
      due to poor follow-up. Treatment options included exploration with HA
      thrombectomy plus thrombolysis, retransplantation, or conservative treatment of
      hepatic and biliary complications. RESULTS: Among 11 patients of mean age 29.98
      +/- 17.14 years (range, 10 months to 56 years). 2 had split right lobe liver
      transplantations and 9 received whole organs. None of LDLTs were identified to
      have HAT. The causes of liver cirrhosis among HAT patients were autoimmune
      hepatitis (n=3), cryptogenic (n=3), Wilson (n=1), PBC (n=1), biliary atresia
      (n=1), and HBs (n=1). HAT was diagnosed at 5.9 +/- 4.43 (range, 2 to 16) days
      after operation. Most patients developed right upper quadrant (RUQ) pain at
      presentation. Two patients developed acidosis, fever, or SIRS and underwent
      retransplantation. Four underwent exploration of HA and 1 was treated
      conservatively. Three cases expired due to HAT complications. CONCLUSION: We
      found RUQ pain to be the presenting sign of early HAT in majority of cases. RUQ
      pain has been reported to occur in late HAT. Whenever HAT is confirmed, liver
      transplanted patients should be revascularized or even retransplanted. Intra
      arterial thrombolysis and thrombolytic therapy for HAT should be done cautiously
      due to the potential risk of hemorrhage.

PMID- 17524931
TI  - The effect of clamping of inferior vena cava and portal vein on urine output
      during liver transplantation.
AB  - BACKGROUND: Intraoperative hypotension, massive transfusion, liver disease,
      coexistent renal dysfunction, and decreased glomerular filtration rate during the
      anhepatic phase are major hazards for kidney function. We undertook this study to
      determine the change in urine output during clamping. METHOD: Twenty-four
      patients without preexistent renal disease, who were undergoing liver
      transplantation using the piggyback method, were enrolled in this study. Patients
      with a serum creatinine level >1.2 mg/dL were excluded. Urine output was
      monitored over 30 minutes before inferior vena cava and portal vein clamping,
      during clamping, and for 30 minutes after declamping. None of the patients had a
      clamping time >70 minutes. Our goal was to maintain mean arterial blood pressure
      and heart rate just by fluid administration diuretics were avoided. RESULTS:
      Participants had a mean age of 39.12 +/- 13.52 years (range, 15-67 years) with a
      male to female ratio of 1:4. Urine output 30 minutes before clamping was 3.64 +/-
      3.58 (range, 1.25-15.18) mL/kg/h, decreased to 1.28 +/- 2.58 (range, 0-11.39)
      mL/kg/h during clamping (P=.00), and increased to 3.56 +/- 3.64 (range, 0.51
      15.18) mL/kg/h 30 minutes after declamping (P=.00). CONCLUSION: Urine output was
      significantly reduced in all patients after clamping of the IVC and portal veins.
      This observation may be explained by increased venous pressure leading to
      decreased renal perfusion pressure. It has been stated that one of the advantages
      of veno-veno bypass (VVB) is increased renal perfusion pressure. However, if the
      clamping time in the piggyback method is <70 minutes and patients have normal
      preoperative renal function, the decreased renal perfusion pressure will not
      cause postoperative kidney dysfunction.

PMID- 17524932
TI  - Effect of rapamycin on wound healing: an experimental study.
AB  - The aim of this study was to investigate the effects of rapamycin (RAPA) on the
      healing of bladder and abdominal wound closures. Fourteen male Sprague Dawley
      rats were randomized to receive either RAPA (3 mg/d) or placebo. A midline
      laparotomy was performed. The bladder was cut and closed with 4-0 Vicryl in a
      double layer. The fascia was closed with 0 nylon suture, and the skin closed with
      a subcuticular 2-0 nylon suture. The mean RAPA level was 9.1 ng/mg. Eosinophil
      and neutrophil infiltration, and the presence and degree of myofibroblast
      proliferation were significantly higher in the bladder, fascia, and dermis of the
      control group. Lymphocyte infiltration was similar in each group. Mean
      microvessel density as well as the percentage of cells expressing vascular
      endothelial growth factor in the bladder, fascia, and dermis were significantly
      lower among the RAPA group. Both proliferating cell nuclear antigen labeling
      indices for inflammatory cells in the fascia, dermal fibroblasts, and epithelial
      cells in the placebo group were significantly higher. No difference was observed
      for hydroxyproline levels in both the bladder and fascia between the groups. In
      conclusion, we found that RAPA treatment affected all steps of the wound healing
      process by decreasing the inflammatory cell number, angiogenesis, and
      myofibroblast proliferation, so the wound healing process was delayed and
      consequently the tensile strength of the wound decreased.

PMID- 17524933
TI  - An assay for the determination of sirolimus levels in the lymphocyte of
      transplant patients.
AB  - Both tacrolimus (TAC) and sirolimus (SRL) bind to the same immunophilin FKBP12;
      however, their mechanisms of action are distinct. SRL inhibits mammalian target
      of rapamycin (TOR), which is an enzyme critical to the immune function. TOR
      inhibition blocks the signal that mediates T-cell proliferation by preventing
      cell-cycle progression from G1 to S phase. Moreover, TOR inhibition results in a
      decrease in antibody production by blocking B-cell proliferation and maturation
      into antibody producing cells. The use of SRL has resulted in a decrease in the
      number of rejection episodes. As with other immunosuppressive agents, SRL can
      cause dose-related side effects, the most notable of which are
      hypercholesterolemia, hyperlipidemia, anemia, and thrombocytopenia. Thus,
      therapeutic drug monitoring to assess efficacy and toxicity has became a
      necessity. SRL blood levels do not correlate with its bioactivity and are
      affected by the concomitant use of other immunosuppressive drugs. To determine
      the bioactivity of SRL we have developed an assay to determine the level of
      Sirolimus per lymphocyte of transplant patients. The levels were correlated with
      lymphocyte count. METHODS: Whole blood samples from patients on SRL were
      collected in Ethylene Diamine Tetra-acetic acid (EDTA) vacutainer tubes.
      Immediately the lymphocytes from 2 mL of blood were separated using 1.5 mL of
      Ficoll gradient, by centrifugation for 30 minutes at 2500 RPM. The lymphocytes
      were washed three times with phosphate-bufferd saline and the pellet suspended in
      150 microL of Middle East research institute (MERI) drug extraction solution
      (Beirut, Lebanon), which was then added to 300 microL of IMx solublizing reagent.
      The cytoplasmic SRL concentrations in lymphocytes were measured using kits
      supplied from Abbott diagnostics or by high-performance liquid tomography. A
      corresponding whole blood sample from each patient was used to measure blood
      levels. To determine the level per lymphocyte, the value obtained was divided by
      the number of lymphocytes and expressed as Pg/cell. A pharmacokinetic profile for
      both blood and lymphocytes was constructed for each patient using data
      corresponding to predose C(0), 1 hour (C(1)) and 2 hours (C(2)) after the dose.
      The lymphocyte enumeration for C(0), C(1), and C(2) was performed using the FACS
      Calibur Flow Cytometer from Becton Dickinson. The average dose was 2.86 +/- 1.27
      mg/d with a C(0) = 8.05 +/- 4.24, C(1) = 21.9 +/- 8.9 ng/mL, and C(2) = 23 +/-
      0.03 ng/mL. Although there was a significant correlation (P=.0975) between the
      dose and C(0), there was no correlation between the dose and C(0) level on the
      lymphocyte count P=.897. However, there was a strong correlation between SRL
      lymphocyte levels (pg/cell) and the lymphocyte count (r(2)=.6.06). The higher the
      concentration of the drug the lower the lymphocyte counts. The assay is sensitive
      to within 0.45 pg/cell, reproducible with a coefficient of variance (CV) of 6.4%
      within assay and 7.5% for intraassay.

PMID- 17524934
TI  - Lymphedema: an unusual complication of sirolimus therapy.
AB  - INTRODUCTION: Lymphedema is an increasingly observed complication of sirolimus
      (SIR) therapy. In this report, we describe four renal recipients with SIR-induced
      lymphedema of varying severity. CASES REPORTS: Patient 1, a 38-year-old man
      developed lymphedema of the left upper limb after being exposed to SIR for 30
      months (mean daily Rapamune dose, 3 mg; trough level, 10-18 ng/mL). Venography
      and duplex ultrasound were normal. Lymphangiography was showed delayed lymphatic
      drainage. SIR was replaced with Prograf with significant improvement in the
      lymphedema over the next 6 months. Patient 2, a 26-year-old woman, developed
      lymphedema of the left lower limb at 24 months after starting SIR (mean daily
      dose, 3 mg; trough level, 10-15 ng/mL). Lymphangiography showed delayed drainage
      of lymphatics in the left lower limb. The patient was shifted to Prograf and
      there was some improvement over the next 4 months. Patient 3, a 28-year-old man,
      developed lymphedema of the left upper limb at 24 months after the start of SIR
      (mean daily dose, 2 mg, trough level, 6-15 ng/mL). Lymphangiography showed
      evidence of lymphatic obstruction. SIR was changed to cyclosporine with only mild
      improvement in lymphedema over the next 6 months. Patient 4, a 46-year-old man,
      developed lymphedema of the right upper limb at 7 months after starting SIR (mean
      daily dose, 6 mg; trough level, 10-16 ng/mL). Lymphangiography showed complete
      blockage of the lymphatic channels. SIR was changed to cyclosporine and there was
      mild improvement in lymphedema over the next 8 to 10 months. CONCLUSION: The
      exact mechanism of SIR-induced lymphedema is unknown. The absence of other
      demonstrable etiologies and spontaneous improvement after discontinuation of SIR
      suggest that this drug was the responsible factor in these four patients. It
      occurred 7 to 30 months after transplantation. This is the fourth such report in
      the literature to the best of our knowledge.

PMID- 17524935
TI  - Tacrolimus-related seizure in the early postoperative period after liver
      transplantation.
AB  - The aim of this study was to analyze liver transplant patients who had tacrolimus
      (TAC)-related seizures at our institution during the early postoperative period.
      Between September 2001 and June 2006, liver transplantation (LT) was performed in
      132 patients. All received a TAC-based immunosuppressive protocol after LT.
      Twelve (9%; 1 woman, 11 men; mean age 20 +/- 12 years; range, 12-49 years) of
      those 132 patients had a seizure during the first month. Three of these patients
      had received grafts from cadaveric donors and nine from living donors. All
      patients presented with generalized tonic-clonic seizures, and most had minor
      symptoms just hours before the attack. Blood TAC levels were within the
      therapeutic range, and there were no other factors that could have initiated a
      seizure at that time. Eleven patients were changed from TAC to cyclosporine
      (CsA), and one was switched to sirolimus. They also received antiepileptic
      therapy. All patients recovered and seizures disappeared. There were no
      nephrotoxicity or surgical complications related to drug conversion. Death
      (unrelated to seizure) occurred in one patient at 2 months after LT. Eleven
      patients are alive with good graft function at a mean follow-up of 20 +/- 19.7
      months (range, 1-52 months). In conclusion, during the early posttransplant
      period, each neurologic disturbance, even a minor one, should alert the
      clinician, as it might be a warning sign of a coming seizure. These patients
      should be followed closely, and the clinician should not hesitate to do a drug
      conversion in suspicious cases.

PMID- 17524936
TI  - Pharmacokinetics, efficacy, and safety of Iminoral compared with Neoral in
      healthy volunteers and renal transplant recipients.
AB  - This study sought to evaluate the bioequivalence of Iminoral (test) versus Neoral
      (reference) in healthy volunteers, as well as safety and efficacy of Iminoral
      treatment in renal transplant recipients following conversion from Neoral.
      METHODS: After an overnight fast, 18 healthy volunteers received the assigned
      treatment (test or reference, 200 mg single dose) in a cross-over fashion with a
      washout period of 14 days. The blood samples were drawn at various times after
      drug administration. Cyclosporine blood concentration was measured by high
      performance liquid chromatography using an ultraviolet detector. In the second
      phase of study, stable renal transplant patients who were on Neoral were enrolled
      in the study in an open-label manner. They were converted from Neoral to Iminoral
      based on a 1:1 dose equivalence. Cyclosporine trough levels and changes in serum
      creatinine, lipid profile, electrolytes, and uric acid were measured before and
      periodically after conversion for 6 months. RESULTS: The 90% confidence interval
      of the test/reference ratio was within the acceptable limits of 0.8 to 1.25.
      Relative bioavailability of Iminoral in healthy subjects was 99.0%. There was no
      significant difference in cyclosporine concentrations and serum creatinines
      following conversion to Iminoral in renal transplant patients (n=41). There were
      no reports of major toxicity or of graft rejection and no need for dose
      adjustment related to Iminoral. CONCLUSIONS: Single doses of Neoral and Iminoral
      are bioequivalent in healthy subjects. Renal transplant recipients maintained on
      Neoral can be safely and effectively converted to Iminoral on a 1:1 conversion
      ratio.

PMID- 17524937
TI  - Low-dose versus high-dose cyclosporine induction protocols in renal
      transplantation.
AB  - BACKGROUND: Current immunosuppressive therapies are effective to prevent acute
      rejection episodes (ARE) and graft loss following renal transplantation. Newer
      agents now make it possible to develop equally efficacious but better tolerated,
      less toxic strategies. We compared the efficacy of early low- versus high-dose
      cyclosporine (CsA) induction therapy in living donor renal transplantation.
      METHODS: In this single-center study, 90 consecutive recipients of living donor
      kidney transplants between November 2002 to October 2003 including 51 females and
      mean average age of 48.23 years were treated with either CsA (5 mg/kg/d) plus
      mycophenolae mofetil (MMF; 30 mg/kg/d) and prednisolone (1 mg/kg/d; group 1;
      n=42); or CsA (8 mg/kg/d) plus MMF (30 mg/kg/d) and prednisolone (1 mg/kg/d;
      group 2; n=48). The 2 groups were matched with respect to age, sex, underlying
      renal diseases, pretransplantation dialysis period, number of transplantations,
      and panel-reactive antibody tests. CsA dose tapering was initiated in the 2 group
      3 months after transplantation. At the end of the first year, the CsA dose was
      3.5 +/- 0.65 mg/kg in group 1 and 3.4 +/- 0.34 mg/kg in group 2. Prednisolone was
      tapered within the first 2 months, reaching 10 mg/d in all patients. The MMF dose
      remained unchanged. The 2 groups were compared with respect to ARE, patient and
      graft survivals, and clinical outcomes within 2 years after transplantation.
      RESULTS: There were no significant differences between the 2 groups with respect
      to clinical outcomes, including 2-year patient survival (97.62% vs 97.92%;
      P=.76), 2-year graft survival (80.32% vs 80.41%; P=.82), ARE (47.61% vs 52.08%;
      P=.09), or length of immediate postsurgical hospital stay, number of
      readmissions, total hospitalization days, posttransplantation diabetes mellitus,
      and infectious, cardiovascular, gastrointestinal, and hematologic complications.
      There was more hypertension (67.5% vs 50.23%; P=.007), hypertriglyceridemia
      (45.5% vs 32.64%; P=.005), and elevated liver enzymes in group 2 (12.5% vs 7.14%;
      P=.018). CONCLUSIONS: Compared with 8 mg/kg CsA induction therapy, the lower
      doses of CsA were effective, well tolerated, and safe with relatively fewer side
      effects.

PMID- 17524938
TI  - Cyclosporine trough (C0) and 2-hour postdose (C2) levels: which one is a
      predictor of graft loss?
AB  - BACKGROUND: Compared with conventionally measured trough level (C0), cyclosporine
      2-hour postdose (C2) concentrations show a better correlation with the area under
      the curve and acute graft rejection. OBJECTIVES: We evaluated the relationships
      of C0 and C2 with long-term graft survival among kidney transplant recipients.
      METHODS: In a case-control design, we selected 215 adult kidney recipients.
      Inclusion criteria were more than 18 years of age at transplantation and at least
      6 months of follow-up. The case group consisted of patients with graft loss
      (n=17) and a control group, patients with functioning grafts (n=198). The C0 and
      C2 levels for the first 6 months posttransplantation, along with demographic and
      clinical data, were compared between the two groups using univariate analysis.
      P<.05 was considered to be significant. RESULTS: The mean age at transplantation
      was 40.5 +/- 16.5 years. The mean follow-up duration was 18 +/- 14 months. The
      mean C0 values for the case and control groups were 257.8 +/- 126.5 and 248.5 +/-
      104.4 mumol/L, respectively (P>.05). The values for C2 were 712.7 +/- 273.2 and
      886.2 +/- 266.9 mumol/L, respectively (P=.01). CONCLUSIONS: We observed that C2,
      but not C0, in the first 6 months posttransplantation were a predictor of long
      term graft survival. The findings here in supported the results of other studies
      that have proposed cyclosporine concentration monitoring by C2 rather than C0
      measurements.

PMID- 17524939
TI  - Single daily dose administration of cyclosporine in renal transplant recipients.
AB  - Cyclosporine (CsA) microemulsion has been the mainstay immunosuppressive agent
      for renal transplant recipients for years. A single daily dosing of cyclosporine
      (SD) is rarely used. The objective of this study was to evaluate the efficacy of
      SD versus twice daily dosing of CsA. Retrospective evaluation of SD use was
      conducted for 44 renal transplant recipients for 12 months (study group). Equal
      numbers of matched recipients were selected for age, sex, HLA mismatch, donor
      type, and immunosuppressive regimen (control group). We measured CsA trough (C0)
      and peak (C2) blood levels, 12-hour CsA profile, and the area under the
      concentration-time curve (AUC). There were significant differences in C0, C2, and
      calculated AUC after shifting to SD. In the study group, the mean AUC was 4619
      ng/mL/h before versus 6567 ng/mL/h after shifting to SD (P=.004). This became
      more therapeutic and identical to the mean AUC in the control group, which was
      6551 ng/mL/h. Total daily CsA dose was significantly lower in the study group
      compared with the control group (P<.0001). A significantly higher incidence of
      hepatitis was observed among the study group (P=.011). There were significantly
      fewer adverse effects in patients in the study group than the control group.
      There were no significant differences in graft and patient outcomes between the
      groups. We concluded that CsA dose should be individualized in renal transplant
      recipients especially if they have viral hepatitis. SD has the advantage of
      decreasing dosage and CsA-related adverse effects while maintaining optimal graft
      function.

PMID- 17524941
TI  - Acid-base status determines cyclosporine-induced hypercalciuria.
AB  - OBJECTIVE: Cyclosporine (CsA) causes tubular dysfunction characterized by
      polyuria, calcium wasting, distal tubular acidosis, and hyperkalemia. The
      hypercalciuria induced by CsA administration is associated with an inhibition of
      calbindin D(28k) expression. It has also been shown that chronic metabolic
      alkalosis increased the expression of Ca(2+) transport proteins accompanied by
      diminished urine Ca(2+) excretion. The aim of this study, therefore, was to
      determine the effect of acid-base status on CsA-induced hypercalciuria. METHODS:
      Experiments were performed on male Sprague-Dawley rats. Metabolic alkalosis and
      acidosis were induced respectively by adding 0.28 mol/L NaHCO(3) and 0.28 mol/L
      NH(4)Cl in the drinking water for 7 days; control rats received regular tap
      water. Seven days after NaHCO(3) or NH(4)Cl administration, rats were treated
      with CsA (25 mg/kg, IP) daily for 14 days. To estimate glomerular filtration rate
      (GFR) over time, animals were placed in metabolic cages. Fractional urinary
      calcium excretion was determined by standard formula. RESULTS: The CsA group
      showed decreased serum calcium and increased fractional urinary calcium excretion
      compared with the control group. Creatinine clearance was also significantly
      reduced. Metabolic alkalosis alone did not affect GFR, but significantly
      prevented an increase in fractional urinary calcium excretion induced by CsA,
      whereas chronic metabolic acidosis resulted in the exact opposite effect.
      CONCLUSIONS: It is essential for nephrologists to fully understand the mechanisms
      of CsA-induced renal injury. In this study, metabolic alkalosis reduced CsA
      induced hypercalciuria. Further studies are needed to elucidate whether this
      effect may be achieved pharmacologically by the expression of Ca(2+) transport
      proteins.

PMID- 17524940
TI  - Effect of orange and tangerine juice on cyclosporine levels in renal transplant
      recipients.
AB  - INTRODUCTION: Cyclosporine Neoral is a major immunosuppressive agent widely used
      in organ transplant populations. Its pharmacokinetics are influenced by various
      factors. The aim of this study was to investigate the effects of orange or
      tangerine juice on the pharmacokinetic pattern of cyclosporine Neoral among renal
      transplanted patients. MATERIALS AND METHODS: Ten renal transplant recipients on
      cyclosporine Neoral-based immunosuppressive therapy were included in this
      crossover controlled study. Patients were given their individualized morning dose
      of cyclosporine with either 250 mL water or 250 mL orange or tangerine juice; 12
      hour cyclosporine pharmacokinetic investigations were performed. The three
      investigation days were separated by at least 7 days. RESULTS: The intake of
      orange juice did not have any significant influence on the area under the curve
      in the interval from 0 to 12 hours (AUC 0-12; 95% confidence interval [CI]: -769
      to 734, P=.77), or the maximum whole blood concentration (Cmax; 95% CI: 264 to
      74; P=.32). Similarly, after coadministration of cyclosporine Neoral with
      tangerine juice, no significant changes were observed in AUC 0-12 (95% CI: -453
      to 1166; P=.28) or Cmax (95% CI: -239 to 179; P=.37). CONCLUSION:
      Coadministration of orange (var Tampson) or tangerine (var Unshiu) juice with
      cyclosporine compared with water did not influence exposure to cyclosporine in
      renal transplant recipients.

PMID- 17524942
TI  - Bioavailability of a new generic formulation of mycophenolate mofetil MMF 500
      versus CellCept in healthy adult volunteers.
AB  - Several studies have revealed a decreased incidence of early graft rejection with
      the use of mycophenate mofetil (MMF). The cost of the drug is, however,
      prohibitive especially in developing countries with limited resources. We
      compared the pharmacokinetic profile of a new MMF generic formulation (MMF 500
      batch number: 06T3001; Medis Tunis) with those of Cellcept, (batch number: M1427;
      Hoffmann La Roche, Switzerland) in healthy volunteers. The study was double
      blinded to investigator and volunteers. It had a balanced randomized, two
      treatment, two-period, two-sequence, single-dose, crossover, comparative oral
      bioavailability design in adult healthy human volunteers. The study was designed,
      performed, and monitored by CRO Transmedical s.a.l International (Beirut,
      Lebanon) in accordance with the Basic Principals defined in the US 21 CFR Part
      312.20, and the principals enunciated in the World Medical Association
      Declaration of Helsinki. We included nonsmoking healthy volunteers between the
      ages of 22 and 45 years. The subjects were admitted to the hospital one night
      prior to blood sampling. After volunteers received the same dinner, they were
      fasted overnight and for 2 hours postdosing. At 8 am each person received a
      single oral dose of 500 mg of either formulation. Blood samples were collected to
      construct the pharmacokinetic profiles as follows: 0, 0.15, 0.30, 0.45 minutes
      and 1, 1.15, 1.30, 2, 4, 6, 10, 12, and 24 hours. Water and food intake were the
      same for all volunteers during the whole study period. Following an 8-day washout
      period, the subjects were crossed over. Plasma mycophenolic acid concentrations
      were determined using a high-performance liquid chromatography validated enzyme
      linked immunosorbent assay-based method (TransMedical, Beirut Lebanon). Physical
      examinations, hematology, urinanalysis, serum chemistry tests, and liver enzymes
      were performed at screening and at the end of each period. Subjects were
      monitored for safety and adverse events throughout the study by two physicians
      (one from the hospital and one from TransMedical). The Cmax, Tmax, and AUC for
      MMF 500 were 10.14 ng/mL, 51.82 minutes, and 18.33 ng/mL/h vs 10.94 ng/mL, 49.09
      minutes, and 17.46 ng/mL/h for CellCept, respectively. The 90% confidence
      intervals (LSM) of Cmax, Tmax, and AUC for MMF 500 were 92.7%, 105.6%, and 105%,
      respectively, which is within the Food and Drug Administration (FDA)-assigned
      range for immunosuppressive drugs (90% to 111%). These results indicated that the
      products are equivalent and switchable according to FDA rulings.

PMID- 17524943
TI  - Changing treatment protocol from azathioprine to mycophenolate mofetil: decrease
      in renal dysfunction, increase in infections.
AB  - INTRODUCTION: Immunosuppression for renal transplantation has shifted from
      azathioprine (AZA) regimens to those containing mycophenolate mofetil (MMF). This
      study investigated the impact of this change on the causes for rehospitalization
      as well as on graft and patient survival. METHODS: In this retrospective cohort
      study, we reviewed long-term patient and graft survivals as well as the causes of
      posttransplant admissions for 893 kidney recipients. Data on survival and
      readmissions were available for 811 subjects, who were divided to into the AZA
      cohort (n=289, transplantation between 1998 and 1999) and the MMF cohort (n=567,
      transplantation between 2000 and 2001). Survival, the cause for readmission, time
      interval between transplantation and readmission, intensive care unit (ICU)
      admission, mortality, and graft loss were compared between the two cohorts.
      RESULTS: Five-year patient and graft survival rates were 85% and 67% for the AZA
      cohort and 91% and 68% for the MMF cohort (P=.013). There were 202 (71%) and 371
      (72%) readmissions registered for the AZA and MMF groups, respectively. In
      comparison with the AZA cohort, while readmissions secondary to graft rejection
      showed a significant decrease in the MMF cohort (62% vs 35%, P=.000),
      readmissions secondary to infections exhibited a significant increase (37% vs
      50%, P=.002). A marginally significant increased mortality rate (2% vs 5%,
      P=.087) and ICU admission rate (3% vs 6%, P=.062) were also observed in the MMF
      cohort by comparison with the AZA cohort. CONCLUSION: The shift in the
      immunosuppression protocol from AZA to MMF, albeit advantageous in many
      instances, can sometimes undermine the outcome by giving rise to such
      complications as high infection rates.

PMID- 17524944
TI  - Optimization of immunosuppressive drug monitoring in children.
AB  - BACKGROUND: The metabolism of drugs in children differs from adults, although
      pediatric pharmacokinetic (PK) studies remain scarce. Many of the drugs are
      metabolized by polymorphically expressed enzymes (cytochrome P450 [CYP450];
      glucuronyl transferase [GT]) and/or transported by drug transporters (ABC and SLC
      families). In children, there is added complexity because of the age dependency
      of drug metabolism. This review addresses the age dependency of drug metabolism
      in childhood on the basis of routine PK monitoring. METHODS: Standard
      pharmacokinetic studies in pediatric renal transplant recipients were analyzed to
      study drug-drug interactions between mycophenolic acid and cyclosporine on the
      one hand, and tacrolimus and sirolimus on the other hand. The exposure was
      compared with age. We also studied sirolimus metabolites, both by mass
      spectrometry as well as using human liver microsomes. RESULTS: We demonstrated
      age dependency for MPA exposure. Independent of the concomitant medication,
      infants required approximately twice as much drug for the same exposure. The drug
      drug interaction between sirolimus and tacrolimus demonstrated age dependency.
      Sirolimus metabolites showed a remarkably different pattern in children. Whereas
      39-O-desmethyl sirolimus is the most prevalent metabolite in adults, we found
      77.5% hydroxylated metabolites in children. Similarly, pediatric human liver
      microsomes produced 86.1% hydroxylated metabolites. CONCLUSIONS: Our long-term
      objective is to develop evidence-based guidelines for age-appropriate drug dosing
      of all drugs commonly used during childhood and adolescence, based on
      pharmacokinetically/pharmacogenetically determined drug exposure to maximize
      therapeutic yield while minimizing toxicity. The potential need for lifelong
      medications warrants efforts to minimize toxicity in chronically ill pediatric
      patients.

PMID- 17524945
TI  - The impact of renal failure on survival following cardiac transplantation.
AB  - OBJECTIVE: Renal failure after cardiac transplantation is a common and serious
      complication. In this study we investigated the incidence and effects of renal
      failure on survival among patients who underwent cardiac transplantation.
      PATIENTS: Eight patients underwent cardiac and one patient combined cardiac and
      renal transplantation. The mean age of the patients was 33 +/- 11.6 years (range,
      17 to 51). On preoperative echocardiographic evaluation, the mean ejection
      fraction was calculated as 19 +/- 3.11% (range, 16% to 24%). One patient had
      compensated renal failure and one patient, dialysis-dependent renal failure.
      Hemofiltration was routinely used during the operations. Corticosteroids,
      cyclosporine, and mycophenolate mofetil were used for immunosuppression. Early
      renal replacement therapy was performed in patients with acute renal failure.
      RESULTS: The incidence of acute renal failure was 55.5% (5 patients). In the
      early postoperative and follow-up periods, the mean ejection fraction was 55 +/-
      9.9% and 57 +/- 4.5%, respectively. The mean follow-up period was 21.3 +/- 8.8
      (range, 6 to 33) months. In the early initiation period, the mean peak value of
      cyclosporine blood level was 479 +/- 201.8 ng/mL during the first month, 250 +/-
      95.3 and after the third month, 195 +/- 43.7 ng/mL. The mean creatinine level at
      last follow-up was 1.27 +/- 0.4. One patient experienced a grade III-A rejection
      episode. One patient died due to coronary artery occlusive disease at 31 months
      after transplantation. COMMENT: In our study we have observed that renal failure
      had no negative effect on patient survival. This can be explained by improved
      cardiac performance, keeping cyclosporine levels low finding and utilizing early
      renal replacement treatment.

PMID- 17524946
TI  - Xenograft transplantation in congenital cardiac surgery at Baskent University:
      midterm results.
AB  - OBJECTIVE: Xenograft valved conduits have been used in several cardiac
      pathologies. In this study we have presented our midterm results of pediatric
      patients pathologies who were operated with xenograft conduits. PATIENTS AND
      METHODS: Between January 1999 and January 2005, 134 patients underwent open heart
      surgery with xenograft conduits. The conduits were used to establish the
      continuity of the right ventricle to the pulmonary artery or aorta, the left
      ventricle to the pulmonary artery, or aorta due to various types of complex
      cardiac anomalies. Patients were evaluated by transthoracic echocardiography
      (ECHO) at 6-month follow-ups. Cardiac catheterization was performed when ECHO
      demonstrated significant conduit failure. RESULTS: Hospital mortality was
      observed in 28 patients (20.1%), and 13 patients died upon follow-up (9.7%). Mean
      follow-up was 24.6 +/- 4 months (range, 13 to 85 months). Among 93 survivors 20
      patients (21.5%) were reoperated due to conduit failure. The main reasons for
      conduit failure were stenosis (n=13), valvular regurgitation (n=2), or both
      conditions in 5 cases. Mean pulmonary gradient before conduit re-replacement was
      47.7 +/- 30.1 mmHg. The 1-, 3-, and 6-year actuarial survival rates were 95 +/-
      2%, 91 +/- 3%, and 86 +/- 5%. The 1-, 3-, and 6-year actuarial freedom rates from
      reoperation were 95 +/- 1%, 90 +/- 3%, and 86 +/- 4%. An increased gradient
      between the pulmonary artery and the right ventricle and prolonged
      cardiopulmonary bypass times were observed to be significant risk factors for
      reoperation. There was no mortality among reoperated patients. CONCLUSION:
      Xenograft conduits should be closely followed for calcification and stenosis.
      Conduit stenosis is the major risk factor for reoperation. In these patients,
      reoperation for conduit replacement can be performed safely before deterioration
      of cardiac performance.

PMID- 17524947
TI  - Comparison of early outcome and histologic findings of enteric drainage with
      bladder drainage in pancreas transplantation of dogs.
AB  - BACKGROUND: The clinical and pathological findings of enteric-drained (ED) versus
      bladder-drained (BD) pancreas transplantation are still controversial. In this
      study, we compared early outcome and histological findings of these 2 methods.
      METHODS: In an experimental animal model, after diabetization, 16 dogs were
      randomly divided into 2 groups. In the first group, the pancreas was transplanted
      with enteric drainage, and in the second group, with bladder drainage. We
      evaluated early clinical and pathological outcomes. RESULTS: The mean survival
      time was 11.25 +/- 5.0 (range, 5-20) days for group 1 and 13.6 +/- 7.2 (range, 3
      23) days for group 2 (P>.05). Fasting blood sugar values (FBS) before
      transplantation were 279 +/- 26.8 mg/dL versus 278 +/- 41.6 mg/dL, respectively
      (P>.05). Two weeks postoperative serum FBS had decreased to 84.9 +/- 2.9 versus
      84.2 +/- 0.98, respectively (P>.05). Serum amylase in the BD and ED groups were
      378.5 +/- 328 versus 422.6 +/- 54.7 mg/dL, respectively (P>.05). Early leakage
      was not observed in dogs with BD, whereas it was 37.5% among dogs with ED
      (P<.05). Clinical and pathological evidences of pancreatic necrosis occurred in
      37.5% of dogs with BD versus 62.5% of dogs with ED (P>.05). DISCUSSION: Although
      the early outcomes of these drainage methods (ED vs BD) were statistically
      similar more dogs with ED experienced early complications than with BD.

PMID- 17524948
TI  - The first 2 years of clinical experience with peripheral blood stem cell
      transplantation for various hematological malignancies: results from a single
      Baskent University Center.
AB  - Autologous stem cell transplantation is the current standard approach for
      patients with multiple myeloma and relapsed or refractory lymphoma.
      Nonmyeloablative allogeneic stem cell transplantation has been applied worldwide.
      We analyzed the results of transplantation activity from 2004 to 2006. Seven
      evaluable patients younger than 65 years old with stage II/III multiple myeloma
      were treated with high-dose melphalan therapy (140 mg/m(2)) plus autologous
      peripheral blood stem cell transplantation. Complete responses or tumor
      reductions of more than 75% were obtained in all patients. At a median follow-up
      of 10 months, all patients remained disease-free. Four patients with acute
      myeloblastic leukemia underwent nonmyeloablative allogeneic peripheral stem cell
      transplantation. Their median age was 30 years. One patient was refractory and
      the others were in hematological remission. The patients received fludarabine
      based preparative regimens. All patients received fully matched blood from a
      related donor 2 days after chemotherapy in conjunction with graft-versus-host
      disease prophylaxis. One refractory patient with >90% engraftment had late
      autologous reconstitution at 3 months with evidence of relapse. All other
      patients in remission remained with >90% donor cell engraftment. These patients
      are disease-free at 13, 10, and 2 months. Toxicity was minimal. These results
      showed promise due to the minimal toxicity observed with the conditioning
      regimens which indicated the feasibility of these procedures.

PMID- 17524949
TI  - Acute renal failure due to leptospirosis in a renal transplant recipient: a brief
      review of the literature.
AB  - We present the case of a 43-year-old renal transplant patient who presented with
      fever, malaise, pruritus, headache, and severe jaundice of 3-week duration
      following work in a rice field. He was found to have acute renal failure and
      severe hyperbilirubinemia with a positive serum leptospira antibody titer, making
      the diagnosis of Weil's disease. The patient responded to reduction in
      immunosuppressive medications and intravenous penicillin therapy with no need for
      dialysis. This is the second case of leptospirosis in a kidney transplant patient
      reported in the English literature.

PMID- 17524950
TI  - Complete regression of cutaneous B-cell lymphoma in a renal transplant patient
      after conversion from cyclosporin to sirolimus.
AB  - Posttransplant lymphoproliferative disease remains a serious morbidity. Herein we
      have reported a case of complete regression of a biopsy-proven B-cell lymphoma
      that occurred in the posttransplant period. A 48-year-old man received a living
      donor renal transplant for end-stage renal disease due to undetermined etiology.
      His initial immunosuppression consisted of corticosteroid, mycophenolate mofetil,
      and cyclosporin. The patient developed severe pneumonia within the first 2 months
      after transplantation due to Acineotobacter, fungus, and cytomegalovirus
      infections. He experienced a complete recovery and was discharged for regional
      follow-up. Four months after discharge, he was referred again because of presence
      of two nodules on his trunk. A biopsy of the nodules revealed B-cell lymphoma.
      Cyclosporin was stopped and he was converted to sirolimus. The lesions regressed
      progressively and completely within 7 weeks. The patient remains well without
      clinical relapses at 19 months after conversion. Renal functions remained stable.
      We postulated that the antincoplastic properties of sirolimus may have played an
      active part in the positive outcome.

PMID- 17524951
TI  - Retinal injury as an early manifestation of posttransplant thrombotic
      microangiopathy: recovery with plasma exchanges and conversion to sirolimus--case
      report and review of the literature.
AB  - Thrombotic microangiopathy (TMA) remains a serious event. We report a case of
      occurrence of TMA in the immediate postoperative period after a living-related
      renal transplantation. A distinguished feature of the case was major, early
      involvement of the retina with marked by decreased visual acuity along with
      thrombocytopenia and renal functional impairment. The syndrome was reversible
      with plasma exchange and conversion from tacrolimus to sirolimus. The patient's
      renal function is excellent at 11 months after transplantation. Decreased visual
      acuity and cotton wool exudates may be the first manifestation of posttransplant
      TMA.

PMID- 17524952
TI  - Post renal transplant Castleman's disease resolved after graft nephrectomy: a
      case report.
AB  - Angiofollicular lymphoid hyperplasia (Castleman's disease) is a
      lymphoproliferative process thought to be mediated by overexpression of II
      interleukin-6. Castleman's disease has two variants: Castleman's disease has two
      variants: Hyaline vascular type and plasma cell variant (multicentric Castleman's
      disease). The hyaline vascular type tends to be localized, and the plasma cell
      variant shows more systematic signs and carriers a worse clinical prognosis.
      Castleman's disease is associated with B-cell lymphoma, Kaposi sarcoma, Human
      herpes virus 8 (HHV-8), and Epstein-Barr virus. Castleman's disease have been
      described thrice post kidney transplant. In this report, we document the course
      of a renal recipient who developed the plasma cell variant of Castleman's disease
      at 16 months after failure of his allograft and return to dialysis. He displayed
      clinical resolution of this complication after graft nephrectomy. To our
      knowledge, this is the first case where the disease manifestations disappeared
      after graft removal. Our patient experienced chronic renal allograft rejection
      which may have driven all the systematic manifestations of multicentric
      castleman's disease and possibly reactivated a latent HHV-8 infection. In this
      case immunohistochemical testing for HHV-8 was not available to prove a role for
      this agent.

PMID- 17524953
TI  - De novo Crohn's disease in a renal transplant recipient.
AB  - The prevalence of inflammatory bowel disease (IBD) after renal transplantation is
      affected by the immune tolerance and the modality of immunosuppression.
      Mycophenolate mofetil (MMF) may have a promoting effect on the development of
      posttransplantation erosive enterocolitis and a Crohn's disease-like pattern of
      colitis. We have presented a 40-year-old man with end-stage renal disease due to
      chronic glomerulonephritis who commenced hemodialysis for 2 months before receipt
      of a live unrelated renal transplant. He developed early posttransplantation
      diabetes mellitus and an anti graft rejection episode, which responded to a
      methylprednisolone pulse and OKT3 treatment. His immunosuppressive regimen
      included prednisolone, MMF, and tacrolimus. Three years after transplantation, he
      developed mild constitutional symptoms, mouth ulcerations, and chronic
      intermittent bloody diarrhea. Colonoscopy showed active segmental colitis with
      aphthous ulcers, involving the proximal descending colon and the splenic flexure.
      Colonic biopsies showed distended and branched crypts in the ascending colon,
      moderate active chronic colitis with regenerative atypia, skipping appearance,
      and ulceration in the splenic flexure and descending colon. The edematous crypts
      were associated with ulcerations in the sigmoid colon and rectum. The features
      were highly suggestive of Crohn's disease. He was successfully treated with high
      dose steroids and 5-aminosalicylic acid. Subsequently, he developed chronic
      transplant glomerulopathy and restarted hemodialysis. We concluded that de novo
      Crohn's disease may develop in renal transplant recipients despite
      immunosuppressive therapy especially with MMF immunosuppression.

PMID- 17524954
TI  - Second-generation endometrial ablation: an overview.
AB  - Various methods exist to destroy the endometrium as a treatment for menorrhagia.
      This chapter discusses the rationale, evidence, indications, and long-term safety
      and efficacy of the current techniques. It also discusses endometrial ablation in
      the context of its clinical utility in comparison with the existing alternative
      treatments.

PMID- 17524955
TI  - Automated coupled-contour and robust myocardium tracking in stress
      echocardiography.
AB  - Dobutamine stress echocardiography is a commonly used imaging modality for the
      diagnosis of coronary artery disease and the detection of myocardial viability.
      The major limitations are that it is operator dependent and that the analysis is
      subjective and qualitative resulting in interobserver variability. It is also
      tedious and time consuming. Consequently, several quantitative approaches have
      been proposed, such as acoustic quantification and color kinesis but none of
      these has proved to be fully quantitative. In this manuscript we describe the
      development of a new, quantitative technique based on tracking of both
      endocardium and epicardium providing information of endocardial excursion and
      myocardial thickening, a crucial parameter of wall function evaluation.
      Preliminary data indicate that the method is practical and feasible, but clinical
      trials are required to prove whether it will improve the sensitivity and
      specificity of dobutamine stress echocardiography.

PMID- 17524956
TI  - The influence of conditioned fear on human pain thresholds: does preparedness
      play a role?
AB  - Emotionally charged facial expressions (happy, fear) served as conditioned
      stimuli in a differential fear conditioning procedure. Expressions were presented
      in pseudo-random order on a computer monitor. For half of the participants, the
      fear expression was paired with an aversive electric stimulation (UCS), whereas
      the happy expression was unpaired. The other participants had the opposite
      pairing. To assess the influence of conditioned fear on pain, expressions were
      shown again in the absence of the UCS and pain threshold was assessed during each
      expression. The latency of finger withdrawal from a radiant heat device was used
      to index pain threshold. Skin conductance response (SCR) and self-reported
      emotion were measured to assess fear conditioning. Consistent with preparedness
      theory, differential fear conditioning was only present when the fear expression
      was paired with the UCS. Moreover, pain threshold was only influenced by fear
      conditioning in persons for whom the fear expression was paired with the UCS.
      Specifically, finger withdrawal latencies were lower (suggesting hyperalgesia)
      during the fear expression than during the happy expression; an effect that was
      not present before CS-UCS pairing. This work suggests that some stimuli are more
      readily associated with an aversive event and can lead to pain enhancement.
      PERSPECTIVE: Although preliminary, these results suggest that fear-relevant
      environmental stimuli (including facial expressions) may provide important
      environmental cues during aversive events that influence the level of pain
      experienced.

PMID- 17524957
TI  - Alterations of intracellular calcium concentration and nitric oxide generation in
      pulmonary artery endothelium after subarachnoid hemorrhage of the rabbit.
AB  - The present study was designed to investigate whether endothelial intracellular
      calcium concentration ([Ca(2+)](i)), endothelial nitric oxide synthase (eNOS)
      activity and nitric oxide (NO) generation altered in association with impaired
      endothelium-dependent relaxation (EDR) in pulmonary artery (PA) specimens from
      experimental subarachnoid hemorrhage (SAH) rabbits. Injecting non-heparinized
      autologous arterial blood into cisterna magna induced the SAH. Simultaneous
      measurements of endothelial [Ca(2+)](i) and isometric tension of PA specimens
      were performed using fura 2. The subjects included normal control rabbits (group
      N), SAH rabbits with normal EDR (group A) and with impaired EDR (group B). When
      treated with 10(-7) M acetylcholine (ACh), endothelial [Ca(2+)](i) was
      significantly lower in group B (74.1+/-8.5 nM) than that in groups A (153.0+/
      28.0 nM, p<0.05) and N (184.8+/-27.8 nM, p<0.01). Basal and ACh-stimulated cyclic
      GMP productions as a marker of NO generation were also significantly (p<0.005)
      decreased in group B as compared to those in the other two groups. Meanwhile,
      there were no differences in eNOS activity per se among the three groups. These
      results suggest that the attenuated endothelial [Ca(2+)](i) elevation leads to
      the impaired NO generation in PA endothelium, which in turn impairs the EDR and
      possibly increases the vascular resistance of PA following SAH.

PMID- 17524958
TI  - Randomized clinical trials with a pre- and a post-treatment measurement: repeated
      measures versus ANCOVA models.
AB  - Repeated measures (RM) and ANCOVA models are compared with respect to treatment
      effect estimation in randomized clinical trials with a pre- and a post-treatment
      measure. The covariance matrices of repeated measures are assumed to be I)
      homogeneous or II) heterogeneous across groups. In situation I, ANCOVA is
      preferred to RM, because the estimated variance of the treatment effect estimator
      is unbiased for ANCOVA and biased downwards for RM. In situation II, RM with
      Kenward and Roger's adjustment is preferred to ANCOVA, because the ANCOVA
      variance estimator does not correct for unknown pre-treatment expectation. The
      results are illustrated with an example.

PMID- 17524960
TI  - Outcomes associated with 12 years of grant funding: the Pediatric Endocrinology
      Nursing Society grant program.
AB  - In 1990, the Pediatric Endocrinology Nursing Society (PENS) developed a grant
      program to provide funding to advance pediatric endocrinology nursing practice
      through basic and applied research. Minimal data exist regarding the effect of
      grant funding on professional development and research dissemination. The purpose
      of this study was to determine the extent that PENS' grant funding has resulted
      in professional presentations, publications, and further research funding.
      Nineteen grants that received funding were identified. Survey questions included
      whether the results of the PENS-funded study were presented, published, and
      resulted in subsequent funding from other sources. Outcome data were available
      for 11 of 18 grants (61%). All funded studies were presented at PENS conference;
      55% were presented at other national or international conferences. Sixteen
      publications resulted from seven funded studies; 64% of PENS' funded studies led
      to additional funding, and 18% resulted in additional research studies. In
      summary, the research grant program of PENS funded 19 grants, which resulted in
      numerous publications, presentations, and, in some cases, additional research
      funding from other sources. Many grant recipients acknowledged that PENS was
      their first source of research funding and gave them the opportunity to become
      experienced in their role as clinical researchers.

PMID- 17524961
TI  - Methodological challenges during 20 years of adolescent research.
AB  - The purpose of the present article was to highlight the methodological challenges
      we have experienced in conducting adolescent research for the past 20 years or
      more. In this article, we describe the methodological issues we have encountered
      with nonexperimental research designs, sampling, instrumentation, data collection
      procedures, statistical analyses, and ethical concerns of adolescent research,
      particularly the process of informed consent. Sharing our experiences with
      adolescent research can shed light on methodological issues (specifically in this
      age group) that are not addressed in research textbooks and can provide guidance
      for other researchers who are interested in developing knowledge relevant to
      adolescent populations.

PMID- 17524962
TI  - Weight status, self-competence, and coping strategies in Chinese children.
AB  - This study aimed to investigate Chinese children's perceptions of self-competence
      and the coping strategies based on gender and weight status using the Terror
      Management Theory. A total of 331 Chinese children completed body mass index
      (BMI), Self-Perception Profile for Children, and Schoolagers' Coping Strategies
      Inventory. Mothers completed demographic information and the Family Assessment
      Device. Results indicated that better behavioral conduct competence contributed
      to better global self-worth in boys; in girls, better behavioral conduct
      competence and physical appearance competence contributed to better global self
      worth. Higher BMI was related to lower athletic competency in boys and lower
      social competence in girls. Eating and drinking were reported as one of the most
      frequently used coping strategies by children, but the children felt that this
      strategy was not effective. Results of this study suggest that culture plays an
      important role in children's perceived self-competence and coping strategies.
      Health care providers and educators should incorporate assessment of self
      competence and coping strategies into patient care and education.

PMID- 17524963
TI  - An update on emergency contraception use in adolescents.
AB  - Changing circumstances regarding access to emergency contraception (EC) warrant
      nurses' review of its current status. Nurses have the potential to improve
      adolescents' awareness of and access to EC so that adolescents may prevent
      pregnancy. Research suggests that adolescents lack awareness of EC methods that
      prevent pregnancy following an unprotected act of intercourse. Many pregnancies
      occurring in adolescence could be prevented with appropriate EC use. Studies show
      that adolescents are capable of using EC correctly and safely, and that access to
      EC is not associated with increased rates of unprotected intercourse or with
      higher rates of pregnancy or sexually transmitted infections.

PMID- 17524964
TI  - Maternal demandingness and responsiveness as predictors of adolescent abstinence.
AB  - This retrospective study examined two distinct parenting dimensions,
      demandingness and responsiveness, as independent predictors of adolescent sexual
      risk behavior. The data used to test study hypotheses were from Waves I and II of
      the National Longitudinal Study of Adolescent Health (Add Health). In this sample
      of 2,030 adolescents and their mothers, maternal demandingness [odds ratio
      (OR)=0.77] and maternal responsiveness (OR=0.89) independently predicted
      adolescent abstinence from sex. Findings substantiate the use of a dimensional
      approach to measuring parenting in examining adolescent sexual behavior.

PMID- 17524965
TI  - Revision and psychometric testing of the Barton Hospital Picture Test.
AB  - The Barton Hospital Picture Test (BHPT) is an instrument designed to elicit self
      reports of stress in hospitalized children. This article reports two studies. The
      results of Study 1 were used to revise the pictures. Study 2 determined the
      reliability and validity of the revised BHPT. The revised BHPT has construct
      validity demonstrated by differences in total stress scores in the expected
      direction between hospitalized and community (well) children. The instrument has
      acceptable test-retest, interrater, and internal consistency reliability.

PMID- 17524966
TI  - Influencing policy development: the whirling dervish of the autism in-home
      program.
AB  - The elimination of a state supported autism in-home program due to budgetary
      constraints is used to illustrate how nurses working with grassroots and
      legislative groups can influence policy, and how policy, in turn, determines the
      availability of treatment and services. Within 24 hours of its elimination,
      parents of children with autism and key stakeholders mounted a statewide advocacy
      effort to restore an autism in-home program that researchers had shown to be
      effective Lovaas, O. I. (1987). Behavioral treatment and normal education and
      intellectual functioning in your autistic children. Journal of Consulting and
      Clinical Psychology, 55, 3-9. The purpose of this paper is to illustrate the
      circuitous route of public policy through the perspective of a nurse practitioner
      who worked at a grass roots level with parents of children with autism and
      legislators to effect policy change related to the program. In addition, the
      paper provides perspectives from a provider of autism in-home services, a parent,
      and a politician stressing the lessons learned in using the political process for
      the benefit of the children.

PMID- 17524967
TI  - Shortage of nurses and child health.

PMID- 17524968
TI  - Children's fear as experienced by the parents of children with cancer.
AB  - It is known that children with cancer experience and express fear, but little is
      found in the literature about how the parents experience their child's fear. This
      study aimed to highlight the parents' lived experience and understanding of their
      child's fear. Focus group interviews with 15 parents were performed. Data were
      analyzed through a phenomenological hermeneutic method. Fear in children with
      cancer is described by the parents as a multidimensional phenomenon, which is
      somehow difficult to identify. It appears in contrast to the absence of fear. The
      comprehensive understanding of the results reveals that the parents experience
      their children's fear as both a suffering and an ethical demand for the parents
      to answer.

PMID- 17524969
TI  - Inpatient surgical bowel preps: making them work.
AB  - This article will describe the evidence-based approach our hospital developed to
      best prepare children for abdominal surgery. Our evidence-based interdisciplinary
      approach was based on the work of [McCallin, A. (2001). Interdisciplinary
      practice--A matter of teamwork: An integrated literature review. Journal of
      Clinical Nursing, 10, 419-428], [Melnyk, B. M. (2002). Evidence-based practice.
      Strategies for overcoming barriers in implementing evidence-based practice.
      Pediatric Nursing, 28, 159-161], [Melnyk, B. M., & Fineout-Overholt, E. (2002).
      Evidence-based practice. Key steps in implementing evidence-based practice:
      Asking compelling, searchable questions and searching for the best evidence.
      Pediatric Nursing, 28, 262-266], [Sierchio, G. P. (2003). A multidisciplinary
      approach for improving outcomes. Journal of Infusion Nursing, 26, 34-43], and
      [Wojner, A. W. (1996). Outcomes management: An interdisciplinary search for best
      practice. AACN Clinical Issues, 7, 133-145]. At our hospital, a leading
      children's hospital in an eastern urban setting, we surgically manage children,
      from newborns to young adults, with a variety of diagnoses. These diagnoses
      include the following: inflammatory bowel diseases, such as Crohn's disease and
      UC, imperforate anus, necrotizing enterocolitis, and abdominal tumors. The bowel
      prep is an integral part of these children's surgical preparation.

PMID- 17524971
TI  - Direct electrochemistry and electrocatalytic characteristic of heme proteins
      immobilized in a new sol-gel polymer film.
AB  - Heme proteins were immobilized on glass carbon electrodes by poly (N-isopropylac
      yamide-co-3-methacryloxy-propyl-trimethoxysilane) (PNM) and exhibited a pair of
      well-defined, quasi-reversible cyclic voltammetric peaks at about -0.35 V versus
      a saturated calomel electrode in pH 7.0 buffer solution, corresponding to
      hemeFe(III)+e-->hemeFe(II). Some electrochemical parameters were calculated by
      performing nonlinear regression analysis of square wave voltammetry (SWV)
      experimental data. The formal potential was linearly dependent on pH, indicating
      the electron transfer of Fe(III)/Fe(II) redox couple accompanied by the transfer
      of proton. Ultraviolet visible and Fourier transform infrared spectra suggested
      that the conformation of proteins in the PNM films retained the essential feature
      of its native secondary structure. Atomic force microscopy images demonstrated
      the existence of interaction between heme proteins and PNM. N,N-dimethylformamide
      (DMF) played an important role in immobilizing proteins and enhancing electron
      transfer between proteins and electrodes. Electrochemical catalytic reductions of
      hydrogen peroxide and trichloroacetic acid by proteins entrapped in PNM film were
      also discussed, showing the potential applicability of the film modified
      electrodes as a biosensor.

PMID- 17524973
TI  - Development of a quantitative LC-MS/MS analytical method coupled with turbulent
      flow chromatography for digoxin for the in vitro P-gp inhibition assay.
AB  - Caco-2 cells, the human colon carcinoma cells, are typically used for screening
      compounds for their permeability characteristics and P-glycoprotein (P-gp)
      interaction potential during discovery and development. The P-gp inhibition of
      test compounds is assessed by performing bi-directional permeability studies with
      digoxin, a well established P-gp substrate probe. Studies performed with digoxin
      alone as well as digoxin in presence of test compounds as putative inhibitors
      constitute the P-gp inhibition assay used to assess the potential liability of
      discovery compounds. Radiolabeled (3)H-digoxin is commonly used in such studies
      followed by liquid scintillation counting. This manuscript describes the
      development of a sensitive, accurate, and reproducible LC-MS/MS method for
      analysis of digoxin and its internal standard digitoxin using an on-line
      extraction turbulent flow chromatography coupled to tandem mass spectrometric
      detection that is amendable to high throughput with use of 96-well plates. The
      standard curve for digoxin was linear between 10 nM and 5000 nM with regression
      coefficient (R(2)) of 0.99. The applicability and reliability of the analysis
      method was evaluated by successful demonstration of efflux ratio (permeability B
      to A over permeability A to B) greater than 10 for digoxin in Caco-2 cells.
      Additional evaluations were performed on 13 marketed compounds by conducting
      inhibition studies in Caco-2 cells using classical P-gp inhibitors (ketoconazole,
      cyclosporin, verapamil, quinidine, saquinavir etc.) and comparing the results to
      historical data with (3)H-digoxin studies. Similarly, P-gp inhibition studies
      with LC-MS/MS analytical method for digoxin were also performed for 21 additional
      test compounds classified as negative, moderate, and potent P-gp inhibitors
      spanning multiple chemo types and results compared with the historical P-gp
      inhibition data from the (3)H-digoxin studies. A very good correlation
      coefficient (R(2)) of 0.89 between the results from the two analytical methods
      affords an attractive LC-MS/MS analytical option for labs that need to conduct
      the P-gp inhibition assay without using radiolabeled compounds.

PMID- 17524972
TI  - 1,2-Dimethylimidazole-4-sulfonyl chloride, a novel derivatization reagent for the
      analysis of phenolic compounds by liquid chromatography electrospray tandem mass
      spectrometry: application to 1-hydroxypyrene in human urine.
AB  - A novel derivatization method employing 1,2-dimethylimidazole-4-sulfonyl chloride
      (DMISC) to improve the mass spectrometric response for phenolic compounds in
      liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) and
      tandem mass spectrometry (LC-ESI-MS/MS) is described. Several environmentally
      relevant compounds, including chloro-, aryl- and alkylphenols, steroidal
      estrogens, and hydroxy-polycyclic aromatic hydrocarbons (OHPAHs), were selected
      to evaluate this technique. A facile derivatization procedure employing DMISC
      results in dimethylimidazolesulfonyl (DMIS) derivatives that are stable in
      aqueous solution. These DMIS derivatives produced intense [M+H](+) ions in
      positive-ion LC-ESI-MS. The product ion spectra of the [M+H](+) ions of simple
      phenols were dominated by ions representing the DMIS and dimethylimidazole
      moieties, whereas product ion spectra of the DMIS derivatives of OHPAHs with
      three or more fused aromatic rings showed prominent ArO(+) ions, the relative
      intensity of which increased with the number of rings. The DMIS derivatives of
      the selected phenolic compounds showed excellent chromatographic properties. To
      substantiate the utility of derivatization with DMISC, an analytical method
      employing enzyme hydrolysis, solid phase extraction, derivatization with DMISC,
      and analysis by LC-ESI-MS/MS with multiple reaction monitoring for determination
      in human urine of 1-hydroxypyrene, a widely used biomarker for the assessment of
      human exposure to PAHs, was developed and validated.

PMID- 17524974
TI  - Quantitative gas chromatographic method for the analysis of cis-9, trans-11 and
      trans-10, cis-12 isomers of the conjugated linoleic acid in liver.
AB  - A quantitative GC method for conjugated linoleic acid (CLA) isomers of
      physiological significance (cis-9, trans-11 CLA and trans-10, cis-12 CLA) as non
      esterified fatty acids (NEFA) or triacylglycerols (TAG) was developed.
      Furthermore, the effect of the internal standard addition point (sample or fat
      extract) was studied. Response linearity, recovery and precision assays,
      detection and quantification limits were determined. Linearity was demonstrated
      over a range from 0.1 to 10 microg/mL. When CLA isomers were present as NEFA, the
      recovery significantly decreased (P< or =0.05) from 76% to 27.1% (cis-9, trans-11
      CLA) and 28.5% (trans-10, cis-12 CLA) when the standards were added to the fat
      extract or to the initial tissue, respectively. As an application, liver samples
      from hamsters fed a diet supplemented with both CLA isomers were analyzed. The
      CLA isomers in liver samples were detected with reasonable reproducibility.

PMID- 17524975
TI  - Microvascular free tissue transfer in reconstruction of the lower limb.
AB  - Reconstruction of the lower extremity using microvascular free tissue transfer
      has been adopted as a routine procedure since the 1980s. Success rates in overall
      free tissue transfer are now as high as 98%. In the lower limb, however, the
      failure rate has been reported to be as high as 15 to 20%. A review of 50
      consecutive microvascular free flaps to the lower extremity was carried out in
      the Ulster Hospital Belfast. The indication for surgery, the flap type, the
      recipient vessel, re-exploration rate, complication rate, success rate and the
      changing pattern in management during the first six years of a single
      consultant's practice was assessed. Six patients (12%) were re-explored for
      anastomotic complications or haematoma. Thrombosis of the arterial anastomosis
      was noted in one case, venous thrombosis in two and haematoma under the flap in
      the remaining three cases. Salvage was successful in four cases, thus producing
      an overall success rate of 96%.

PMID- 17524976
TI  - Antitumor effects of clinical dosing regimens of bisphosphonates in experimental
      breast cancer bone metastasis.

PMID- 17524977
TI  - DNA made of purines only.

PMID- 17524978
TI  - Exploiting green treasures.

PMID- 17524979
TI  - Control of oxygenation in lipoxygenase and cyclooxygenase catalysis.
AB  - Lipoxygenases (LOX) and cyclooxygenases (COX) react an achiral polyunsaturated
      fatty acid with oxygen to form a chiral peroxide product of high regio- and
      stereochemical purity. Both enzymes employ free radical chemistry reminiscent of
      hydrocarbon autoxidation but execute efficient control during catalysis to form a
      specific product over the multitude of isomers found in the nonenzymatic
      reaction. Exactly how both dioxygenases achieve this positional and stereo
      control is far from clear. We present four mechanistic models, not mutually
      exclusive, that could account for the specific reactions of molecular oxygen with
      a fatty acid in the LOX or COX active site.

PMID- 17524980
TI  - Molecular similarity analysis uncovers heterogeneous structure-activity
      relationships and variable activity landscapes.
AB  - We systematically compare X-ray structures of inhibitor complexes of four well
      known enzymes and correlate two- and three-dimensional (2D and 3D) similarity of
      inhibitors with their potency. The analysis reveals the presence of unexpected
      systematic relationships between molecular similarity and potency. These findings
      explain why apparently inconsistent structure-activity relationships (SARs) can
      coexist in different targets, and they have general implications for compound
      screening and optimization. The results suggest that (1) even for active sites
      with significant binding constraints, there is a high probability that
      structurally diverse ligands with similar activity can be identified, (2)
      different types of SARs are not mutually exclusive, and (3) the chemical nature
      of ligands is of comparable importance for SARs as the features of active sites.
      These insights aid in the understanding of target-specific SARs and their
      intrinsic degree of variability.

PMID- 17524981
TI  - Design, synthesis, and evaluation of in vivo potency and selectivity of
      epoxysuccinyl-based inhibitors of papain-family cysteine proteases.
AB  - The papain-family cathepsins are cysteine proteases that are emerging as
      promising therapeutic targets for a number of human disease conditions ranging
      from osteoporosis to cancer. Relatively few selective inhibitors for this family
      exist, and the in vivo selectivity of most existing compounds is unclear. We
      present here the synthesis of focused libraries of epoxysuccinyl-based inhibitors
      and their screening in crude tissue extracts. We identified a number of potent
      inhibitors that display selectivity for endogenous cathepsin targets both in
      vitro and in vivo. Importantly, the selectivity patterns observed in crude
      extracts were generally retained in vivo, as assessed by active-site labeling of
      tissues from treated animals. Overall, this study identifies several important
      compound classes and highlights the use of activity-based probes to assess
      pharmacodynamic properties of small-molecule inhibitors in vivo.

PMID- 17524982
TI  - Alkyl-CoA disulfides as inhibitors and mechanistic probes for FabH enzymes.
AB  - The first step of the reaction catalyzed by the homodimeric FabH from a
      dissociated fatty acid synthase is acyl transfer from acyl-CoA to an active site
      cysteine. We report that C1 to C10 alkyl-CoA disulfides irreversibly inhibit
      Escherichia coli FabH (ecFabH) and Mycobacterium tuberculosis FabH with relative
      efficiencies that reflect these enzymes' differential acyl-group specificity.
      Crystallographic and kinetic studies with MeSSCoA show rapid inhibition of one
      monomer of ecFabH through formation of a methyl disulfide conjugate with this
      cysteine. Reaction of the second subunit with either MeSSCoA or acetyl-CoA is
      much slower. In the presence of malonyl-ACP, the acylation rate of the second
      subunit is restored to that of the native ecFabH. These observations suggest a
      catalytic model in which a structurally disordered apo-ecFabH dimer orders on
      binding either the first substrate, acetyl-CoA, or the inhibitor MeSSCoA, and is
      restored to a disordered state on binding of malonyl-ACP.

PMID- 17524983
TI  - An unusual mode of DNA duplex association: Watson-Crick interaction of all-purine
      deoxyribonucleic acids.
AB  - Nucleic acid duplexes associating through purine-purine base pairing have been
      constructed and characterized in a remarkable demonstration of nucleic acids with
      mixed sequence and a natural backbone in an alternative duplex structure. The
      antiparallel deoxyribose all-purine duplexes associate specifically through
      Watson-Crick pairing, violating the nucleobase size-complementarity pairing
      convention found in Nature. Sequence-specific recognition displayed by these
      structures makes the duplexes suitable, in principle, for information storage and
      replication fundamental to molecular evolution in all living organisms. All
      purine duplexes can be formed through association of purines found in natural
      ribonucleosides. Key to the formation of these duplexes is the N(3)-H tautomer of
      isoguanine, preferred in the duplex, but not in aqueous solution. The duplexes
      have relevance to evolution of the modern genetic code and can be used for
      molecular recognition of natural nucleic acids.

PMID- 17524984
TI  - Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed
      with small-molecule inhibitors highlight active-site flexibility.
AB  - The potential for the use of Clostridial neurotoxins as bioweapons makes the
      development of small-molecule inhibitors of these deadly toxins a top priority.
      Recently, screening of a random hydroxamate library identified a small-molecule
      inhibitor of C. botulinum Neurotoxin Serotype A Light Chain (BoNT/A-LC), 4
      chlorocinnamic hydroxamate, a derivative of which has been shown to have in vivo
      efficacy in mice and no toxicity. We describe the X-ray crystal structures of
      BoNT/A-LC in complexes with two potent small-molecule inhibitors. The structures
      of the enzyme with 4-chlorocinnamic hydroxamate or 2,4-dichlorocinnamic
      hydroxamate bound are compared to the structure of the enzyme complexed with L
      arginine hydroxamate, an inhibitor with modest affinity. Taken together, this
      suite of structures provides surprising insights into the BoNT/A-LC active site,
      including unexpected conformational flexibility at the S1' site that changes the
      electrostatic environment of the binding pocket. Information gained from these
      structures will inform the design and optimization of more effective small
      molecule inhibitors of BoNT/A-LC.

PMID- 17524985
TI  - Identification of a type III thioesterase reveals the function of an operon
      crucial for Mtb virulence.
AB  - Rv0098 is part of an operon, Rv0096-Rv0101, from Mycobacterium tuberculosis (Mtb)
      that is essential for Mtb's survival in mouse macrophages. This operon also
      contains an acyl carrier protein and one of the only two nonribosomal peptide
      synthases in Mtb. Rv0098 is annotated in the genome as a hypothetical protein and
      was proposed to be an acyl-coenzyme A (CoA) dehydratase. The structure of Rv0098,
      together with subsequent biochemical analysis, indicated that Rv0098 is a long
      chain fatty acyl-CoA thioesterase (FcoT). However, FcoT lacks a general base or a
      nucleophile that is always found in the catalytic site of type II and type I
      thioesterases, respectively. The active site of Mtb FcoT reveals the structural
      basis for its substrate specificity for long-chain acyl-CoA and allows us to
      propose a catalytic mechanism for the enzyme. The characterization of Mtb FcoT
      provides a putative function of this operon that is crucial for Mtb
      pathogenicity.

PMID- 17524986
TI  - Effects of photochemically activated alkylating agents of the FR900482 family on
      chromatin.
AB  - Bioreductive alkylating agents are an important class of clinical antitumor
      antibiotics that crosslink and monoalkylate DNA. Here, we use a synthetic,
      photochemically activated derivative of FR400482 to investigate the molecular
      mechanism of this class of drugs in a biologically relevant context. We find that
      the organization of DNA into nucleosomes effectively protects it against drug
      mediated crosslinking, while permitting monoalkylation. This modification has the
      potential to lead to the formation of covalent crosslinks between chromatin and
      nuclear proteins. Using in vitro approaches, we found that interstrand
      crosslinking of free DNA results in a significant decrease in basal and activated
      transcription. Finally, crosslinked plasmid DNA is inefficiently assembled into
      chromatin. Our studies suggest pathways for the clinical effectiveness of this
      class of reagents.

PMID- 17524987
TI  - Biosynthesis and structure of aeruginoside 126A and 126B, cyanobacterial peptide
      glycosides bearing a 2-carboxy-6-hydroxyoctahydroindole moiety.
AB  - Aeruginosins represent a group of peptide metabolites isolated from various
      cyanobacterial genera and from marine sponges that potently inhibit different
      types of serine proteases. Members of this family are characterized by the
      presence of a 2-carboxy-6-hydroxyoctahydroindole (Choi) moiety. We have
      identified and fully sequenced a NRPS gene cluster in the genome of the
      cyanobacterium Planktothrix agardhii CYA126/8. Insertional mutagenesis of a NRPS
      component led to the discovery and structural elucidation of two glycopeptides
      that were designated aeruginoside 126A and aeruginoside 126B. One variant of the
      aglycone contains a 1-amino-2-(N-amidino-Delta(3)-pyrrolinyl)ethyl moiety at the
      C terminus, the other bears an agmatine residue. In silico analyses of the
      aeruginoside biosynthetic genes aerA-aerI as well as additional mutagenesis and
      feeding studies allowed the prediction of enzymatic steps leading to the
      formation of aeruginosides and the unusual Choi moiety.

PMID- 17524988
TI  - Structure-activity-based design of a synthetic malaria peptide eliciting
      sporozoite inhibitory antibodies in a virosomal formulation.
AB  - The circumsporozoite protein (CSP) of Plasmodium falciparum is a leading
      candidate antigen for inclusion in a malaria subunit vaccine. We describe here
      the design of a conformationally constrained synthetic peptide, designated UK-39,
      which has structural and antigenic similarity to the NPNA-repeat region of native
      CSP. NMR studies on the antigen support the presence of helical turn-like
      structures within consecutive NPNA motifs in aqueous solution. Intramuscular
      delivery of UK-39 to mice and rabbits on the surface of reconstituted influenza
      virosomes elicited high titers of sporozoite crossreactive antibodies. Influenza
      virus proteins were crucially important for the immunostimulatory activity of the
      virosome-based antigen delivery system, as a liposomal formulation of UK-39 was
      not immunogenic. IgG antibodies elicited by UK-39 inhibited invasion of
      hepatocytes by P. falciparum sporozoites, but not by antigenically distinct P.
      yoelii sporozoites. Our approach to optimized virosome-formulated synthetic
      peptide vaccines should be generally applicable for other infectious and
      noninfectious diseases.

PMID- 17524989
TI  - Structure of Saccharomyces cerevisiae chitinase 1 and screening-based discovery
      of potent inhibitors.
AB  - Chitinases hydrolyse the beta(1,4)-glycosidic bonds of chitin, an essential
      fungal cell wall component. Genetic data on a subclass of fungal family 18
      chitinases have suggested a role in cell wall morphology. Specific inhibitors of
      these enzymes would be useful as tools to study their role in cell wall
      morphogenesis and could possess antifungal properties. Here, we describe the
      crystallographic structure of a fungal "plant-type" family 18 chitinase, that of
      Saccharomyces cerevisiae CTS1. The enzyme is active against 4-methylumbelliferyl
      chitooligosaccharides and displays an unusually low pH optimum for activity. A
      library screen against ScCTS1 yielded hits with Ki 's as low as 3.2 microM.
      Crystal structures of ScCTS1 in complex with inhibitors from three series reveal
      striking mimicry of carbohydrate substrate by small aromatic moieties and a
      pocket that could be further exploited in optimization of these inhibitors.

PMID- 17524992
TI  - Optometric initiatives addressing the global imperative for providing accessible
      eye and vision care worldwide.

PMID- 17524993
TI  - Which certification is for you?

PMID- 17524994
TI  - Tricuspid valve regurgitation induced by endomyocardial biopsy after heart
      transplantation.

PMID- 17524995
TI  - Endomyocardial biopsy-related tricuspid regurgitation after orthotopic heart
      transplantation: single-center experience.
AB  - BACKGROUND: Damage of tricuspid valve (TV) with resultant tricuspid regurgitation
      (TR) induced by endomyocardial biopsy (EMB) following heart transplantation has
      been reported in several studies. This study tried to determine the prevalence of
      EMB-related iatrogenic damage over tricuspid apparatus following orthotopic heart
      transplantation and to evaluate its impact on the patients. METHODS: Fifty
      patients received orthotopic heart transplantation between July 1987 and March
      2005. Eleven patients were excluded from the study due to early postoperative
      mortality or inadequate follow-up. The medical records of the remaining 39
      patients were reviewed retrospectively for basic characteristics as well as each
      attempted EMB. The iatrogenic damage of tricuspid apparatus and serial change of
      TR were accessed with 2-D and Doppler echocardiography. The obtained data were
      analyzed for their statistical significance with SPSS (version 12.0). RESULTS: A
      total of 373 biopsies were performed on the 39 patients between 1987 and 2005.
      The follow-up duration was 42.9+/-26.7 months. The prevalence of TR immediately
      following heart transplantation was 84.6%, with only 25.6% of patients having
      moderate or severe TR. At the end of the follow-up, the prevalence of TR
      increased to 92.3% and 61.5% of patients having moderate or severe TR,
      respectively. Eight patients (20.5%) had small chordae rupture (SCR) noted after
      6.6+/-3.2 biopsies, and 10 patients (25.6%) had flail tricuspid valve (FTV) after
      5.7+/-5.1 biopsies. Of patients with SCR, 62.5% had progression of TR, and 70% of
      patients with FTV showed significant TR change. CONCLUSION: The prevalence of
      iatrogenic tricuspid apparatus damage was high in this study. It contributed to
      the progression of TR significantly regardless of the damage severity.
      Measurements should be taken for prevention of iatrogenic tricuspid apparatus
      damage induced by EMB.

PMID- 17524996
TI  - Outcome of kidney transplantation using organs from executed prisoners: is it
      justified beyond the ethical issue?
AB  - BACKGROUND: Kidney transplantation using organs from executed prisoners is a
      subject of controversy from the viewpoint of ethics. However, few reports have
      addressed the clinical outcome beyond the ethical issue. METHODS: Between January
      1990 and September 2004, a total of 435 kidney transplant recipients (group M)
      who underwent transplantation in 26 different hospitals in China were followed up
      at our hospital. It is believed that all the organs came from executed prisoners.
      The clinical data were retrieved and compared to those of 200 kidney transplant
      recipients (group T) who underwent transplantation in our hospital during the
      same period. RESULTS: There was no significant difference between these 2 groups
      (T vs. M) in terms of hepatitis B virus infection (10.5% vs. 12.1%) or surgical
      complication rate (6.5% vs. 5.6%). The 1st-year acute rejection rate was
      significantly lower in group M (31.1% vs. 24.5%, p=0.015). The 1-year, 5-year,
      and 10-year patient survival rates were 94.3%, 89.5%, and 85.2%, respectively,
      for group T and 92.6%, 83.6%, and 76.7%, respectively, for group M (p>0.05); the
      corresponding graft survival rates were 91.4%, 82.6%, and 66.9%, respectively,
      for group T and 91.6%, 80.0%, and 61.4%, respectively, for group M (p>0.05). When
      patients were stratified according to the year of transplantation, patients who
      underwent transplantation between 2000 and 2004 had significantly better graft
      survival rates in both groups. CONCLUSION: We conclude that kidney
      transplantation using organs from executed prisoners had a clinical outcome
      similar to that of transplantation performed in our hospital during the same
      period.

PMID- 17524997
TI  - A clinical trial of 3 doses of transdermal 17beta-estradiol for preventing
      postmenopausal bone loss: a preliminary study.
AB  - BACKGROUND: It is well documented that a daily oral dose of 0.625 mg of
      conjugated equine estrogen or 1-2 mg of 17beta-estradiol is needed to prevent
      postmenopausal bone loss. Recent studies have indicated that a lower dose of
      estrogen maybe as effective in maintaining bone mass. The purpose of this study
      was to evaluate the effects of 3 dosages of transdermally administered 17beta
      estradiol gel in postmenopausal women stratified by oophorectomy and natural
      menopause. METHODS: One hundred and twenty postmenopausal women were randomly
      selected to form 4 groups. Three groups of women were treated with a transdermal
      administration of estradiol gel at a daily dosage of 1.25, 2.5 and 5.0 g
      (containing 0.75, 1.5, and 3 mg of 17beta-estradiol/day), respectively. The 4th
      group of women, receiving estriol 2 mg/day p.o., was studied concurrently as a
      control. Bone mineral density was measured by quantitative computed tomography of
      the vertebrae from T12 to L3 at baseline, then at 6-month intervals for 1 year.
      RESULTS: Women in all groups receiving 17beta-estradiol gel obtained a
      significant increase in bone mass, with the exception of the 1.25 g/day group,
      which showed a minimal increment at the 6-month period, compared with the control
      group. Comparisons of the increments in bone mass after estrogen therapy for both
      natural and surgical menopausal subjects found that there was a more prominent
      response in surgical menopausal women receiving a dosage of 2.5 g/day.
      CONCLUSION: Estradiol gel at the dosage of 1.25 g/day, equivalent to 17beta
      estradiol 0.75 mg/day, effectively prevented bone loss in postmenopausal women
      after a 12-month treatment period. The therapeutic effect of estradiol gel on
      bone mass was more prominent in the surgical menopausal groups at the dosage of
      2.5 g/day. The atrophic ovaries may therefore play a crucial role in the
      subsequent decades of postmenopausal women.

PMID- 17524998
TI  - Nasal NK/T-cell lymphoma: computed tomography and magnetic resonance imaging
      findings.
AB  - BACKGROUND: Primary nasal natural killer (NK)/T-cell lymphoma is the most common
      cellular subtype seen in nasal lymphomas. It is rare in the Western population
      but occurs more frequently in Asia, South America, and Mexico. The purpose of
      this study was to describe the computed tomography (CT) and magnetic resonance
      (MR) imaging findings of primary nasal NK/T-cell lymphoma. METHODS: During the
      period between January 1990 and June 2006, the CT (n=24) and MR (n=6) images of
      24 patients with biopsy-proved nasal NK/T-cell lymphoma were reviewed
      retrospectively. Both CT and MR images were evaluated for site and extent of
      disease and for pattern of involvement of adjacent areas. RESULTS: The most
      common symptoms at presentation were nasal obstruction, nasal discharge, and
      epistaxis. There was involvement of the unilateral nasal cavity in 16, bilateral
      nasal cavity including nasal septum in 5 and nasal choana in 3. Sites of
      extension outside the nasal cavity included tumor extension into paranasal
      sinuses (n=15), nasopharynx (n=5), nasal labial fold (n=3), oropharynx (n=2),
      infratemporal fossa (n=2), other subcutaneous soft tissue of the face (n=2) and
      anterior cranial fossa base (n=1). Bony destruction was demonstrated in 18 cases,
      involving the sinus bony wall (n=15), nasal turbinate (n=10), lamina papyracea
      (n=6), orbital floor (n=3), and hard palate (n=2). Regional lymphadenopathy was
      also detected in 3 patients with nasal NK/T-cell lymphoma. CONCLUSION: The CT and
      MR appearances of nasal NK/T-cell lymphoma are nonspecific, and the diagnosis
      requires histologic confirmation. However, the differential diagnosis of nasal
      NK/T-cell lymphoma should be included if the images present soft tissue of the
      nasal cavity with bony erosion or destruction; involvement of the orbital cavity,
      nasopharynx and infratemporal fossa; and subcutaneous or nasolabial fold soft
      tissue infiltration, especially in Asian populations.

PMID- 17524999
TI  - Entrapment of a Swan-Ganz catheter.
AB  - Failure to withdraw a catheter is related primarily to catheter entrapment or
      knotting. Placement of a Swan-Ganz catheter is associated with various
      complications, one of which is entrapment. Entrapment of a Swan-Ganz catheter in
      the heart, vena cava, or pulmonary artery is a very rare and serious complication
      that may lead to life-threatening complications if not treated appropriately.
      Most reported cases of catheter entrapment have been associated with surgical
      sutures, artificial valves, or abnormal cardiac anatomy. Here we report a rare
      case of Swan-Ganz catheter entrapment resulting from inserting an excessive
      length of Swan-Ganz catheter into the heart. The catheter was removed smoothly
      under fluoroscopic guidance.

PMID- 17525000
TI  - Intrasellar symptomatic salivary gland rest.
AB  - Ectopic salivary gland tissue in sellar turcica is frequently observed in
      microscopic examination at autopsy. This tissue is considered clinically silent.
      Only 2 symptomatic cases have been previously reported. Here we report a 28-year
      old woman presenting with galactorrhea and hyperprolactinemia. Magnetic resonance
      imaging revealed a 6 x 5-mm nodule in the posterior aspect of the pituitary
      gland. This nodule showed isointensity on T1- and T2-weighted images and less
      enhancement on post-contrast T1-weighted images. Transsphenoidal exploration
      revealed a cystic lesion within the pituitary gland, which consisted of a grayish
      gelatinous content. The pathologic examination confirmed the diagnosis of
      salivary gland rest.

PMID- 17525001
TI  - Fertility preservation with treatment of immature teratoma of the ovary.
AB  - Fertility preservation for a patient with advanced immature teratoma of the ovary
      is reported. The patient, a 29-year-old woman, delivered a healthy baby after
      having had ovarian immature teratoma, grade 3, uncertain stage, at 13 years of
      age. She was initially treated with unilateral salpingo-oophorectomy and a
      contralateral wedge resection for tumor invasion, followed by a 6-course
      cisplatin+vinblastine+bleomycin regimen, a second operation, and an additional 6
      course etoposide and cisplatin regimen with complete remission. The patient
      delivered a healthy baby 16 years after the initial treatment. Based on this
      successful case, intensive fertility-preserving surgery followed by chemotherapy,
      even in advanced-stage immature teratomas of the ovary, may be effective in
      preserving the reproductive function of women with malignant immature teratomas
      of the ovary.

PMID- 17525002
TI  - Intraosseous ganglion cyst of the capitate treated by intralesional curettage,
      autogenous bone marrow graft and autogenous fibrin clot graft.
AB  - We report a very rare case of intraosseous ganglion cyst of the capitate in a 54
      year-old female who complained of a painful right wrist mass for 1 year. Computed
      tomography study showed an expansile osteolytic lesion with sclerotic margin and
      thinning of the cortex. Combined soft tissue ganglion cyst was also noted at
      operation and confirmed by pathologic study. The case was treated by a new method
      of autogenous bone marrow and fibrin clot graft after intralesional curettage.
      After a 2-year follow-up, the capitate revealed complete bony union and the
      symptoms were relieved with good functional results.

PMID- 17525003
TI  - Effects of atorvastatin on ventricular late potentials and repolarization
      dispersion in patients with hypercholesterolemia.
AB  - Emerging evidence suggests that statins have a favorable impact on the reduction
      of arrhythmia events and sudden cardiac death in patients with structural heart
      disease. We aimed to investigate the possibly and directly favorable effects of
      statins on ventricular late potentials, QT dispersion, and transmural dispersion
      of repolarization attained by analyzing clinical electrocardiography (ECG) risk
      stratification parameters in patients with hypercholesterolemia without
      structural heart disease. In total, 82 patients (45 females; mean age, 62 +/- 10
      years) with hypercholesterolemia were enrolled in this prospective study to
      examine the effects of statin therapy (atorvastatin 10 mg/day for 3 months) on
      ECG risk stratification parameters. Surface 12-lead ECG and signal-average ECG
      (SAECG) were recorded before and after statin treatment. The SAECG parameters, QT
      dispersion, Bazett-corrected QT (QTc) dispersion, T wave peak-to-end interval
      (Tpe), and percentage of Tpe/QT interval were calculated and compared before and
      after statin therapy. Twelve-lead ambulatory 24-hour ECGs were recorded in 12
      patients. The results demonstrated that after statin therapy for 3 months, serum
      levels of total cholesterol and low-density lipoprotein cholesterol were
      significantly reduced (both p values < 0.001). However, neither significant
      changes of each SAECG parameter nor the frequency of late potentials were
      demonstrated after atorvastatin therapy. In addition, no significant changes in
      QT dispersion, QTc dispersion, Tpe, or Tpe/QT were found. However, 24-hour
      ambulatory ECG revealed a flattening effect of circadian variation of QTc
      dispersion after atorvastatin therapy. In conclusion, the favorable
      antiarrhythmia effect of atorvastatin (10 mg/day) therapy cannot be directly
      reflected by analyzing these noninvasive ECG risk stratification parameters in
      low-risk patients with hypercholesterolemia.

PMID- 17525004
TI  - PON1 activity is inversely related to LDL apoB carbonyl content in patients with
      coronary artery disease.
AB  - The objective of this study was to investigate apolipoprotein B (apoB) carbonyl
      content as a parameter for studying low-density lipoprotein (LDL) oxidation in
      coronary artery disease (CAD) risk assessment and to explore the relationship
      between apoB carbonyl content (an index of protein oxidation) and paraoxonase 1
      (PON1) activity in CAD patients and controls. A total of 200 patients suffering
      from CAD and 150 normal individuals were included in the present study. CAD
      patients were classified into two groups on the basis of associated risk factors
      (diabetes mellitus, hypertension): group 1 (n = 120; CAD patients with associated
      risk factors) and group 2 (n = 80; CAD patients with no associated risk factors).
      All subjects were assayed for apoB carbonyl content, LDL-malondialdehyde (LDL
      MDA), PON1 activity, and lipid and apolipoprotein levels. ApoB carbonyl content
      was significantly (p < 0.01) raised in CAD patients (with or without associated
      risk factors) as compared to controls. Patients also had relatively raised LDL
      MDA levels. Serum PON1 activity was significantly low (p < 0.01) in CAD patients.
      A significantly (p < 0.01) negative coefficient of correlation was observed
      between apoB carbonyl content and PON1 activity in both patients and controls.
      CAD patients with associated risk factors had highly raised (p < 0.01) apoB
      carbonyl content and considerably depressed PON1 activity compared to those with
      no associated risk factors. LDL-MDA levels did not differ significantly (p >
      0.05) between the two groups. CAD patients in group 1 also had significantly
      raised apoB levels and low HDL-cholesterol and apoA1 levels as compared to
      patients in group 2, while the other lipid variables did not show any significant
      difference. A significantly negative coefficient of correlation was observed
      between apoB carbonyl content and PON1 activity in both patients and controls.
      This is a new piece of information that needs to be further explored.
      Quantification of apoB carbonyl content may act as a suitable parameter for
      studying LDL oxidation in the evaluation of CAD risk, especially when confounding
      risk factors are present.

PMID- 17525005
TI  - Effects of functional electrical stimulation on peak torque and body composition
      in patients with incomplete spinal cord injury.
AB  - The aim of this study was to investigate the change in body composition, leg
      girths, and muscle strength of patients with incomplete spinal cord injury (SCI)
      after functional electrical stimulation cycling exercises (FESCE). Eighteen
      subjects with incomplete SCI were recruited. Each patient received FESCE three
      times per week for 8 weeks. Body composition, thigh and calf girths of bilateral
      legs, muscle strength of bilateral knee flexors and extensors were measured
      before and after 4 and 8 weeks of FESCE. A significant increase in bilateral
      thigh girth after 4 weeks of FESCE and significant increase in muscular peak
      torque of knee flexion and extension were found after 8 weeks of training.
      Besides, lean body mass increased significantly after complete treatment. FESCE
      can increase the thigh girth and muscular peak torque of patients with incomplete
      spinal cord injury.

PMID- 17525006
TI  - Management of symptomatic urolithiasis during pregnancy.
AB  - Urinary calculi during pregnancy present not only a diagnostic challenge but also
      a management dilemma. In this retrospective study, we describe our experience
      with diagnosis and management of symptomatic urolithiasis in pregnant women. A
      total of 18 pregnant women were treated for urolithiasis at the Department of
      Urology, Kaohsiung Municipal Hsiao-Kang Hospital, between 1999 and 2004. The
      incidence of symptomatic urolithiasis during pregnancy was 0.35%. Of the 20
      stones found, nine were on the right side and 11 were on the left, and two
      patients had bilateral urinary stones. Most urolithiasis cases during pregnancy
      (55.5%) occurred in the third trimester. Flank pain (94.4%) was the most common
      clinical presentation. Conservative management was successful in 10 patients
      until the end of pregnancy and then definite treatment was performed. In four
      patients, a double-J stent was inserted successfully for persistent pain. In
      three cases with persistent pain, failure of double-J stent placement was treated
      with ureteroscopic lithotripsy under epidural anesthesia. One patient received
      percutaneous nephrostomy for persistent renal colic and pyonephrosis.
      Ultrasonographic evaluation of pregnant women with suspected renal colic is a
      reasonable diagnostic procedure. Ureteroscopy is another choice when conservative
      treatment fails.

PMID- 17525007
TI  - Deliberate self-harm and relationship to alcohol use at an emergency department
      in eastern Taiwan.
AB  - Suicide incidence has increased dramatically in recent years in Taiwan. In 2004,
      3,468 lives were lost due to suicide and the total mortality was 15.3/100,000. It
      is well known that alcohol drinking raises the risk of deliberate self-harm
      (DSH), especially among psychologically distressed subjects. This study
      investigated the characteristics of DSH patients and their association with acute
      alcohol drinking. Since 2004, an injury surveillance system has been set up in a
      medical center, collecting the minimal information recommended by the World
      Health Organization. Attending nurses collected information and assessed each
      injured patient as to whether he/she smelled of alcohol. Medical records of DSH
      injuries were reviewed for confirmation of any prior DSH and any known mental
      disorder was checked. Of 11,837 injuries, 123 (1.0%) were DSH. Those who were
      first-time DSH patients (n = 115) were studied. About half of the patients were
      female and 83.5% were aged between 20 and 54 years. More than half of the DSH
      incidents occurred at home and 80.1% cases were stabbing or cutting injuries.
      Injuries were defined as alcohol-related based on the report of "alcohol odor''
      or "intoxicated'' by the nurse or a positive blood alcohol test. In total, 55
      (47.8%) DSH injuries were found to be alcohol-related. The proportion of alcohol
      related injuries was highest (60.0%) in the age range 45-64 years. Of those
      patients who tested positive for alcohol (n = 21), the mean blood alcohol
      concentration was 211.2 mg/dL (standard deviation, 79.1). Most subjects were
      discharged from the emergency department (75.7%). Only 20 DSH patients (17.1%)
      went on to receive a psychiatric consultation. DSH is not uncommon in eastern
      Taiwan. Half of our cases were associated with alcohol use. Males had the same
      risk of injuring themselves and were more likely than females to adopt "severe"
      methods to injure themselves. Further studies into the causes of DSH or
      parasuicide attempts are needed. Psychiatric consultation is essential in caring
      for DSH patients and in preventing suicide. ADSH injury also offers an
      opportunity to recognize alcohol problems.

PMID- 17525008
TI  - Acute pancreatitis complicated with transient portal venous thrombosis in one
      patient with hepatocellular carcinoma and cirrhosis.
AB  - Portal venous thrombosis (PVT) is a condition associated with high morbidity. The
      etiologies of PVT include intra-abdominal inflammation or infection, surgical
      intervention, abdominal malignancies such as hepatocellular carcinoma (HCC) and
      pancreatic carcinoma, or abnormality in coagulation caused by various reasons
      such as liver cirrhosis. Management of PVT should be based on its etiology and
      the condition of the patient. We describe a cirrhotic patient with HCC who
      suffered from acute pancreatitis. PVT in the main trunk was detected at admission
      due to the episode of acute pancreatitis. The etiology of thrombosis was
      considered to be inflammation around the main portal trunk caused by pancreatitis
      rather than cirrhosis or HCC. We did not instigate any management for the
      thrombosis. Acute pancreatitis was relieved after conservative treatment. Follow
      up imaging study performed 46 days after detection of thrombosis showed
      spontaneous complete resolution of the thrombus. Our experience may provide
      useful information for the management of such patients.

PMID- 17525009
TI  - Treatment of transplant ureteral stricture with Acucise endoureterotomy: case
      report and literature review.
AB  - We report a patient who was diagnosed with end-stage renal disease and who
      received renal transplantation in her right iliac fossa in 2003. After
      transplantation, right hydronephrosis was noted on abdominal ultrasonography and
      right lower ureteral stricture was diagnosed by antegrade pyelography. She
      received ureter internal stent insertion three times, but hydronephrosis and
      urinary tract infection recurred after the stent was removed. Therefore, Acucise
      endoureterotomy was used to treat the recurrent ureteral stricture. The patient
      was discharged on the second postoperative day and abdominal ultrasonography
      revealed no hydronephrosis during regular follow-up.

PMID- 17525010
TI  - Adenocarcinoma originating from a mature teratoma of the testis.
AB  - Malignant transformation in testicular teratomas has been reported very rarely in
      the literature. Although testicular teratomas in childhood are regarded as benign
      neoplasms, these tumors, if left untreated until advanced ages, may present the
      risk of malignant transformation. We report a case of differentiated
      adenocarcinoma originating from colonic glands in primary testicular teratoma.

PMID- 17525011
TI  - Variable gene cassette patterns of class 1 integron-associated drug-resistant
      Escherichia coli in Taiwan.
AB  - This study characterized class 1 integrons in Escherichia coli in Taiwan. The
      stability and changes in gene cassettes inserted into integrons were also
      evaluated. The study included 436 clinical strains of E. coli isolated in 2002.
      Class 1 integrons were characterized by polymerase chain reaction and direct
      sequencing. Genetic localization of class 1 integrons was determined by conjugal
      transfer and Southern hybridization. The results indicated that 64% of E. coli
      isolates carried class 1 integrons. Molecular analysis revealed that the class 1
      integrons harbored 13 different antimicrobial resistance gene cassettes and two
      unknown gene cassettes; the predominant cassettes were aadA and dfrA. Novel gene
      cassettes first recovered from E. coli were aacA4 and linF. Cassette arrays orfD
      aacA4-catB8 and aadA1-linF were also observed. Gene cassette dfrA12-orfF-aadA2
      was stable. The class 1 integron and dfrA17-aadA5 gene cassette were located on
      the same transferable plasmids and were capable of transmission. Therefore, the
      increased drug resistance of clinical isolates may be explained by antibiotic
      selective pressure and widespread presence of integrons. Under antibiotic
      selective pressure, gene cassette-mediated resistance may not be easily lost. The
      potential role of integrons in the uptake and dissemination of resistance genes
      by plasmid between species of bacteria may decrease the therapeutic effectiveness
      of antibiotics.

PMID- 17525012
TI  - Clinical presentation of acute scrotum in young males.
AB  - The purpose of this study was to assess the clinical presentation and
      ultrasonographic findings of acute scrotum in young males. A total of 87 patients
      (<or= 25 years old) with presentation of acute scrotum were retrospectively
      analyzed in Kaohsiung Medical University Hospital. The patients were divided into
      three groups according to their final diagnosis: 41 patients with testicular
      torsion (TT), eight patients with torsion of the testicular appendage (TTA), and
      38 patients with epididymo-orchitis (EO). The mean ages of the TT group (14.0 +/-
      5.7 years) and EO group (16.6 +/- 7.6 years) were higher than that of the TTA
      group (10.0 +/- 3.5 years) (p = 0.02). White blood cell count (> 10,000
      cells/microL) was not found to be statistically different among groups. Pyuria
      was found in 10 (26%) patients with EO. Color Doppler ultrasound has high
      sensitivity (87.9%) and specificity (93.3%) rates to differentiate TT from other
      causes of acute scrotum. In cases with a lower risk of TT, we suggest that a
      technically adequate color Doppler ultrasound may be arranged to help
      differentiate diagnoses and prevent needless surgery. The importance of emergent
      management for acute scrotum should also be impressed upon the public through
      education to avoid delayed presentation to medical facilities.

PMID- 17525013
TI  - A meta-analysis of the association between stress and health in Taiwan.
AB  - This study adopted the meta-analysis technique to analyze 354 journal articles,
      theses, and dissertations that had investigated the association between stress
      and health in Taiwan between January 1980 and December 2003. This study was
      conducted with the purpose of understanding the association between general
      stress and general health, the discrepant associations between different stress
      types and health facets, and the possible moderators between general stress and
      general health. A computer search for relevant studies was conducted on several
      databases using the key words "stress" and "life event". For each eligible study,
      the important study characteristics were recorded, and the effect sizes of the
      relationship between stress and health were computed. Furthermore, in order to
      investigate the moderating effects of the study characteristics on the stress
      health relationship, the methods of categorical model analysis and correlation
      analysis were employed. The results of this study revealed that: (1) the
      correlations between general stress and general health as well as between general
      stress and various health facets fell between medium and high; (2) there existed
      different degrees of association between various stress types and health facets;
      and (3) none of the demographic and methodologic variables could by itself
      moderate the relationship between general stress and general health as the
      moderator effects were not sufficient and strong enough. This study presents a
      multidimensional framework of the issues on the relationship between stress and
      health, and it provides guiding references for future research. No evidence was
      found for moderating effects of social support, coping strategies, and
      personality traits on the stress-health relationship. Such findings may be due to
      methodologic limitations. This suggests that further investigation is needed.

PMID- 17525014
TI  - Clinical study of uric acid urolithiasis.
AB  - Uric acid urolithiasis develops from various causes. To investigate the clinical
      and biochemical presentation of patients with uric acid urolithiasis, a
      retrospective study was designed. A total of 46 cases were enrolled between
      January 2004 and December 2005. The compositions of the stones were analyzed by
      infrared spectrophotometry. There were 39 males (84.8%) and seven females
      (15.2%), with a mean age of 61.5 +/- 10.6 years and mean body mass index (BMI) of
      26.7 +/- 3.1 kg/m2. The stone location was kidney in 10 (21.7%), ureter in 22
      (41.8%), and bladder in 14 (30.5%). Multiple stones were diagnosed in 36 patients
      (78.3%). Pre-existing comorbidities included diabetes mellitus in 11 patients
      (23.9%), hypertension in 23 (50%), gout in 13 (28.2%), and benign prostatic
      hyperplasia in 14 (30.4%). Mean serum creatinine and uric acid was 1.6 +/- 0.6
      mg/dL and 7.6 +/- 1.8 mg/dL, respectively. There were 27 patients (58%) with
      creatinine > 1.4 mg/dL. The mean urinary pH was 5.42 +/- 0.46. Patients with uric
      acid urolithiasis were predominantly male, older, with higher BMI, multiple stone
      presentation, with lower urinary pH, and hyperuricemia. Exacerbation of the renal
      function should also be of concern because of the high proportion of patients
      with renal insufficiency diagnosed in this study.

PMID- 17525015
TI  - Dynamic magnetic resonance imaging used in evaluation of female pelvic prolapse:
      experience from nine cases.
AB  - Prolapse of pelvic organs in a female can be simple or complex. To make a
      definite diagnosis of pelvic prolapse preoperatively, dynamic magnetic resonance
      (MR) is an alternative to conventional fluoroscopic or sonographic examination,
      with the advantage of providing greater details, and thus helping the surgeon to
      have a good preoperative plan. Nine women suffering from pelvic prolapse with or
      without urinary stress incontinence underwent dynamic MR imaging examination
      (1.0T Magnex100/HP, Shimadzu, Kyoto, Japan) before surgery. All patients were
      examined in the supine position. A single-shot ultra-high speed scan (FE/8/3.02
      20 degrees, 128, 100%-100% 1 NEX 1 slice 10 mm L1.0 second) was used to obtain
      midline sagittal images, with the patients at rest and during pelvic strain. MR
      images were then obtained every 4 seconds. Each examination was analyzed, based
      on specific measurements, to determine the presence and extent of prolapse of
      pelvic organs. The pubococcygeal, levator hiatus width and muscular pelvic floor
      relaxation lines, and the angle of the levator plate were identified. Based on
      these measurements, multicompartment involvement in the pelvic prolapse was
      confirmed in five patients (5/9). Four patients (4/9) had single compartment
      involvement. Seven patients underwent surgery. All patients reported significant
      improvement in their symptoms and signs after surgical intervention. Two patients
      had an almost complete recovery. MR demonstrated simple or complex organ descent
      in all pelvic compartments, and may become a standard preoperative examination
      for pelvic floor abnormalities. The MR images facilitated comprehensive planning
      by the surgeon; thus, they can increase the success rate and help to accurately
      predict the outcome of the surgical intervention. The surgeons also expressed
      high postsurgical satisfaction with the information provided by dynamic MR.

PMID- 17525016
TI  - Management of tracheal deformity during intubation: a case report.
AB  - Failure or difficulty in intubating the trachea can be either due to inability to
      visualize the glottis or some pathology at the level of or below the cords. This
      report describes a case of difficult intubation suspected of being related to
      neck scarring from previous surgery. Computed tomography (CT) was used to
      evaluate the patient's airway and revealed upper tracheal angulation. We describe
      a method to secure the airway in this patient with a two-person technique by
      rotating an oral endotracheal tube 180 degrees counterclockwise to adjust to the
      curvature of the trachea. Problems with intubation should be anticipated in
      patients with scarring of the neck, and equipment for aiding intubation should be
      on hand. Furthermore, we found that CT contributed to the assessment of the
      difficulty of intubation in this kind of patient.

PMID- 17525017
TI  - Congenital left circumflex coronary artery atresia detected by 64-slice computed
      tomography: a case report.
AB  - A variety of coronary artery disorders, including intramyocardial coronary
      segments and coronary artery anomalies, can result in sudden cardiac death,
      especially in young adults. The detection of structural coronary artery
      abnormalities is important in the management of patients at risk of sudden
      cardiac death. Coronary artery anomalies occur in about 1% of the population.
      Congenital absence of left circumflex coronary artery (LCX) is a very rare
      vascular anomaly, and few cases have been reported in the literature, with a
      frequency of only 0.003% in all patients who underwent coronary angiography.
      Although coronary catheterization is the gold standard for the evaluation of
      coronary arterial patency disease, noninvasive computed tomography (CT) is
      considered the diagnostic method of choice for the detection and evaluation of
      coronary artery anomaly. Herein, we report the case of a 17-year-old girl who
      presented with exertional dyspnea and chest pain and who was studied at our
      emergency department with the final diagnosis of LCX atresia detected by 64-slice
      CT. She may be the first case of congenital LCX atresia proved by multislice CT.

PMID- 17525018
TI  - Large vesicula seminalis cyst: a very rare cause of constipation and male
      infertility.
AB  - We report a 35-year-old male patient with chronic constipation and infertility
      for 4 years. Spermiogram revealed severe oligospermia. An external mass
      compressing the rectum was found during rectal examination and flexible
      rectosigmoidoscopy. Abdominal computed tomography showed a presacral cystic mass
      which displaced the bladder anteriorly. The cyst was completely removed with open
      surgery. Histopathologic analysis revealed a cystic lesion covered with squamous
      epithelium including polymorphonuclear leukocytes, macrophages and sperm cells.
      After the operation, the patient's symptoms were relieved. We considered that the
      constipation was caused by external compression by the vesicula seminalis cyst.
      In cases of constipation with infertility, vesicula seminalis cyst should be kept
      in mind.

PMID- 17525019
TI  - Non-invasive alternatives to the Wada test in the presurgical evaluation of
      language and memory functions in epilepsy patients.
AB  - The cognitive outcome of the surgical removal of an epileptic focus depends on
      the assessment of the localisation and functional capacity of language and memory
      areas which need to be spared by the neurosurgeon. Traditionally, presurgical
      evaluation of epileptic patients has been achieved by means of the intracarotid
      amobarbital test assisted by neuropsychological measures. However, the advent of
      neuroimaging techniques has provided new ways of assessing these functions by
      means of non-invasive or minimally invasive methods, such as anatomical and
      functional magnetic resonance imaging, positron emission tomography, single
      photon emission computed tomography, transcranial magnetic stimulation,
      functional transcranial Doppler monitoring, magnetoencephalography and near
      infrared spectroscopy. This paper aims at comparing and evaluating the
      traditional and recent preoperative approaches from a neuropsychological
      perspective.

PMID- 17525020
TI  - Presurgical evaluation in refractory epilepsy secondary to meningitis or
      encephalitis: bilateral memory deficits often preclude surgery.
AB  - We investigated the clinical features and surgical outcome of 17 patients with
      refractory epilepsy secondary to CNS infection who were referred to a tertiary
      center for presurgical evaluation. Six patients had a history of meningitis and
      11 patients had a history of encephalitis. Median age at infection was three
      years (40 days-40 years). Time to seizure onset was shorter in the encephalitis
      group (median of 0.9 years versus 5.9 years in the meningitis group). MRI showed
      unilateral mesial temporal sclerosis (MTS) in all but one patient with meningitis
      (5/6). MRI in the encephalitis group showed unilateral MTS (four patients),
      bilateral MTS (three), porencephalic cysts (one) or no significant findings
      (three). Seizure semiology, following analysis of 127 seizures, included
      automotor seizures, complex motor/hypermotor seizures, dialeptic seizures and
      bilateral asymmetric tonic seizures. Neuropsychological assessment in patients
      with MTS frequently showed bilateral memory impairment (7 out of 12 MTS
      patients), even in 4 patients with unilateral MTS, precluding epilepsy surgery.
      Six patients (two meningitis and four encephalitis patients) underwent a temporal
      lobe resection. All patients are either seizure-free (Class 1a) or are having
      only auras after surgery. One patient from the meningitis group underwent
      functional hemispherectomy and he is also seizure-free. In our series, MTS was
      the most common finding in refractory epilepsy after CNS infections. Bilateral
      memory deficits were often encountered in patients with MTS, even when
      unilateral, these deficits being a limiting factor for surgery. Good surgical
      outcome can be expected in selected patients with unilateral MTS and congruent
      memory deficits.

PMID- 17525021
TI  - Complex partial status epilepticus is an unrecognised feature in SESA syndrome:
      new insights into its pathophysiology.
AB  - We report a patient diagnosed as having subacute encephalopathy with frequent
      seizures in alcoholics (SESA syndrome), in which recurrent, non-convulsive
      seizures of frontal origin contributed significantly to the alteration of the
      mental state. Our case suggests that the occurrence of episodes of complex
      partial status epilepticus (CPSE) may contribute greatly to the origin and
      pathophysiology of the confusional state in this rare, epileptic entity.

PMID- 17525022
TI  - Atypical case of Aicardi-Goutieres syndrome with late-onset myoclonic status.
AB  - Aicardi-Goutieres syndrome (AGS) is a rare, progressive, autosomal recessive
      encephalopathy characterised by basal ganglia calcifications, chronic CSF
      lymphocytosis, and negative serological investigations for the common prenatal
      infections. The clinical profile is characterised by acquired microcephaly, mild
      to severe cognitive delay and dystonia. Epilepsy is usually not prominent. We
      report on a 19-year-old patient with an atypical clinical course, characterized
      by a relatively benign presentation at onset. Epilepsy with complex-focal
      seizures, possibly with a visual aura and sometimes with secondary
      generalization, started at the age of nine years. Clinical deterioration occurred
      later, and at the age of 17 years he experienced severe, generalized, myoclonic
      attacks lasting hours, which were partly controlled by the administration of
      piracetam.[Published with video sequences].

PMID- 17525023
TI  - Temporal lobe dual pathology in malignant migrating partial seizures in infancy.
AB  - A child had the characteristic clinical and EEG pattern of migrating partial
      seizures in infancy with left temporal lobe atrophy, hippocampal sclerosis and
      cortical-subcortical blurring. Seizures were drug-resistant, with recurring
      episodes of status epilepticus. The child developed microcephaly with arrest of
      psychomotor development. Focal brain lesions, in the context of migrating partial
      seizures, have not been previously reported.[Published with video sequences].

PMID- 17525024
TI  - Focal motor seizure with automatisms in a newborn.
AB  - Continuous synchronized video-EEG-polygraphic recordings allow us to better
      define the electroclinical patterns of epileptic events and to study the
      semiological features of neonatal seizures. Recently, complex behaviours and
      motor automatisms in newborns have been reported as being epileptic in nature.
      However, the debate on physiopathology (cortical or brainstem release phenomena)
      is ongoing. We present the synchronized video-EEG documentation of epileptic
      complex motor behaviours in a newborn male. Our case contributes to the
      discussion regarding the semiological classification of the neonatal
      seizures.[Published with video sequences].

PMID- 17525025
TI  - "Tonic-absence seizures": an unusual seizure phenotype, but not necessarily in
      that order.
AB  - Video telemetry in a 15-year-old boy with moderate learning difficulties revealed
      episodes of staring and cessation of activity, followed by sudden stiffening of
      the body for several seconds, abduction of the arms and a brief vocal utterance
      ("ugh"). Each episode lasts around 30 seconds, 3-4 times/day despite treatment.
      The EEG showed generalized 3-4Hz spike-wave discharges during the "absence"
      period followed immediately by a run of fast polyspikes typical of a tonic
      seizure, terminating in a run of 1-2 Hz sharp-slow wave complexes. Although tonic
      absence seizures have been reported rarely, the clinical sequence appears to be
      reversed in this patient, with the occurrence of "absence-tonic" attacks. We
      present video documentation of such attacks and discuss their nosology.[Published
      with video sequences].

PMID- 17525026
TI  - Magnetoencephalographic studies of focal epileptic activity in three patients
      with epilepsy suggestive of Lennox-Gastaut syndrome.
AB  - PURPOSE: To determine the electromagnetic sources of localized epileptic
      activities using magnetoencephalography (MEG) in three adult patients with
      epilepsy suggestive of Lennox-Gastaut syndrome (LGS). METHODS: MEG and
      simultaneous electroencephalography (EEG) were recorded from three adult patients
      using a 204-channel, whole-head MEG system. Equivalent current dipoles (ECDs)
      were calculated for epileptic spikes on MEG according to the single dipole model.
      RESULTS: In two patients, MEG showed epileptiform discharges restricted to the
      unilateral temporal area, corresponding to the EEG spikes. The ECDs calculated
      from these MEG spikes were clustered in the unilateral temporal lobe. In our
      third patient, MEG spikes appeared in the right centroparietal area; ECDs were
      located to the right parietal lobe. CONCLUSIONS: The sources of epileptiform
      discharges that were detected in a restricted area were localized to specific
      parts of the brain cortex. Despite certain limitations (small number of patients;
      atypical late-onset epilepsy in one) our study suggests that MEG may prove to be
      a useful tool for investigating electromagnetic features of localized epileptic
      discharges in patients with LGS. Based on these preliminary results, further
      studies performed in patients with typical LGS features are justified.

PMID- 17525027
TI  - Chronic PLEDs with transitional rhythmic discharges (PLEDs-plus) in remote
      stroke.
AB  - Background. Periodic lateralized epileptiform discharges (PLEDs) are a rare
      phenomenon in electroencephalography, occurring in acute structural brain
      lesions. In general, PLEDs appear transiently in acute lesions, but a few reports
      have described persistent PLEDs in chronic lesions. Case report. An 86-year-old
      female was admitted, in 1999, with a left MCA stroke associated with right hand
      focal motor seizures. The first EEG in February of 2002 showed PLEDs over the
      left hemisphere associated with rhythmic discharges (PLEDs-plus). The patient was
      admitted on a second occasion in 2003 because of three sequential seizures and
      the EEG showed a similar pattern. Finally in 2006, the patient was admitted again
      because of sequential complex partial seizures and an EEG showed the same PLEDS
      plus pattern as the EEGs of 2002 and 2003. Discussion. We report an unusual case
      of chronic PLEDs associated with rhythmic discharges in a patient with recurrent
      seizures and remote stroke.

PMID- 17525028
TI  - Over-interpretation of electroclinical and neuroimaging findings in syncopes
      misdiagnosed as epileptic seizures.
AB  - Syncope and epileptic seizures share some common clinical characteristics that
      may complicate the diagnostic process. In clinical practice, syncope is
      frequently misdiagnosed as an epileptic seizure and consequently treated with
      antiepileptic drugs. In this study, we identified 57 patients with syncope
      (diagnosis based on accepted criteria) who had come to our unit with a previous
      diagnosis of definite epilepsy in 30 cases (syncope misdiagnosed as epileptic
      seizures, SMS), or suspected epilepsy in the remaining 27 cases (unrecognized
      syncope, US). We attempted to identify factors underlying misdiagnosis by
      reviewing clinical findings, particularly potentially confounding features, and
      EEG/neuroimaging data. Finally, we compared these two groups of patients to
      search for crucial elements that had led to misdiagnosis. Although some clinical
      elements were found to be confounding in both groups, it was the interpretation
      of the EEG and MRI findings, particularly when combined with the confounding
      clinical features that constituted the main reasons for misdiagnosis.

PMID- 17525029
TI  - Video-EEG in syncopal attack due to ocular compression in an adolescent
      mistreated for epilepsy.
AB  - Vasovagal syncope can be confused with epileptic seizure. In this situation, eye
      compression may be performed during EEG. We present a video-EEG of a patient in
      whom eye compression produced a typical syncope. Before this recording, the
      patient had been treated for five years with sodium valproate because of a
      misdiagnosis of epilepsy. The diagnosis of neurally-mediated syncope was not
      difficult on the basis of the clinical history, but the reproduction of syncope
      reinforced the correct diagnosis. Ocular compression is now only indicated in
      exceptional circumstances and should be performed with precautions. The video of
      this episode in an adolescent should be of considerable educational value to
      those who are confronted to diagnostic work-up of transient loss of
      consciousness.

PMID- 17525030
TI  - Unrecognized paroxysmal ventricular standstill masquerading as epilepsy: a Stokes
      Adams attack.
AB  - Recognition of cardiac syncope masquerading as epilepsy may be difficult in the
      Emergency Department. We report a middle-aged man with recent onset convulsions
      who posed a diagnostic puzzle before it was found that he had paroxysmal
      ventricular standstill with complete atrioventricular block: he made a complete
      recovery after temporary pacemaker insertion. The main lessons from this case
      were (1) a convulsive seizure of only seconds duration and with an abrupt return
      of consciousness suggests syncope not epilepsy, (2) repeated, convulsive syncopes
      without provocation suggest cardiac syncope, (3) a 12-lead ECG should be recorded
      as soon as possible after such a series of episodes and should not be
      discontinued until an event is captured, and (4) Emergency Department clinicians
      should be familiar with any automatic gain on their ECG machine, lest fast,
      atrial activity be mistaken for narrow complex tachycardia. In summary, a good
      clinical history is of prime importance in differentiating convulsive syncope
      from epilepsy, and a simple, non-invasive cardiovascular evaluation may help to
      diagnose the condition as cardiac syncope.

PMID- 17525031
TI  - Spinal algetic-tonic seizures manifesting as paroxysmal "positive" Brown-Sequard
      syndrome.
AB  - We report on a patient suffering from symptomatic spinal attacks in the form of a
      paroxysmal "positive" (algetic-tonic) Brown-Sequard syndrome. A cervical cord
      lesion, presumably inflammatory-demyelinating in origin, was identified as the
      morphological correlate of these attacks. Their pathogenesis is discussed in the
      light of similar case reports from the literature. For the first time, this rare
      type of seizure is published with a video documentation. It may deserve
      consideration in the differential diagnosis of otherwise unexplained paroxysmal
      events that present in an "epileptic" manner.

PMID- 17525033
TI  - A case of congenital bilateral perisylvian syndrome due to bilateral
      schizencephaly.
AB  - A case of congenital bilateral perisylvian syndrome (CBPS) associated with
      bilateral perisylvian schizencephaly in a 24-year-old woman is reported. She
      presented the classical clinical triad of CBPS, which included congenital facio
      masticatory diplegia, epilepsy and only mild mental retardation, despite the
      presence of bilateral, open-lip clefts in the perisylvian region. We hypothesize
      that the minimal loss of cortical tissue, along with the possible sparing of
      vital white matter association fibers and neuronal plasticity might have
      contributed to the better functional outcome in this patient.

PMID- 17525032
TI  - Status gelasticus associated with levetiracetam as add-on treatment.
AB  - We report the case of a five-year-old girl, presenting with difficult-to-treat,
      symptomatic focal epilepsy, who developed status gelasticus following the
      introduction of levetiracetam as add-on treatment to oxcarbazepine and diazepam.
      Gelastic seizures were documented by video-EEG and were responsive to i.v.
      administration of diazepam. A possible causative role of levetiracetam is
      suggested. Specific susceptibility to some AEDs is also discussed, as this
      patient, at the age of four years, had presented an episode of non-convulsive
      status epilepticus, following introduction of tiagabine, in association with
      vigabatrin and nitrazepam.[Published with video sequences].

PMID- 17525035
TI  - Centralisation of complex pathologies in honours of excellence. How to do it?

PMID- 17525034
TI  - Genetics of epilepsy: epilepsy research foundation workshop report.
AB  - The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006,
      brought together basic scientists, geneticists, epidemiologists, statisticians,
      pharmacologists and clinicians to consider progress, issues and strategies for
      harnessing genetics to improve the understanding and treatment of the epilepsies.
      General principles were considered, including the fundamental importance of clear
      study design, adequate patient numbers, defi ned phenotypes, robust statistical
      data handling, and follow-up of genetic discoveries. Topics where some progress
      had been made were considered including chromosomal abnormalities,
      neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal
      cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics
      were reviewed. Principles and limitations of collaboration were discussed.
      Presentations and their matched discussions are produced here. There was optimism
      that further genetic research in epilepsy was not only feasible, but might lead
      to improvements in the lives of people with epilepsy.

PMID- 17525036
TI  - High tension: oncologic pain.

PMID- 17525037
TI  - Molecular determinants of invasion in endometrial cancer.
AB  - Endometrial carcinoma is the most common gynaecological malignancy in the western
      world and the most frequent among infiltrating tumours of the female genital
      tract. Despite the characterisation of molecular events associated with the
      development of endometrial carcinoma, those associated with the early steps of
      infiltration and invasion in endometrial cancer are less known. Deep myometrial
      invasion correlates with more undifferentiated tumours, lymph-vascular invasion,
      node affectation and decreased global survival. In this review we present an
      overview of the molecular pathology of myometrial infiltration that defines the
      initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as
      a main player of epithelial to mesenchymal transition, as well as modifications
      on other molecules involved in cell-cell contacts, render cells with a migratory
      phenotype. In addition, altered signalling pathways and transcription factors
      associate with myometrial invasion, histologic grade and metastasis.

PMID- 17525039
TI  - Cancer epidemiology: study designs and data analysis.
AB  - Among the scientific interests of cancer epidemiology is the identification of
      both environmental and genetic factors associated with cancer development.
      Observational designs requiring sophisticated methodology are applied to control
      for potential confounding factors. The enormous biotechnological potential
      developed in the last two decades has allowed the integration of a plethora of
      new biomarkers in epidemiological studies to better define the exposure and
      "neoclassic" outcomes, as well as incorporating genetic susceptibility factors in
      both classical and new epidemiological designs. The integration of scopes,
      objectives, data and tools coming from different disciplines also benefits
      epidemiology, thus evolving into "systems epidemiology". In this manuscript, we
      review the basic concepts of study designs and data analysis and introduce
      readers to the more innovative aspects that are now being applied in
      epidemiological studies.

PMID- 17525038
TI  - Hypoxia-inducible factors and cancer.
AB  - Decreased oxygen availability is a common feature during embryonic development as
      well of malignant tumours. Hypoxia regulates many transcription factors, and one
      of the most studied is the hypoxia-inducible factor (HIF). As a consequence of
      HIF stabilisation, the cell constitutively upregulates the hypoxic programme
      resulting in the expression of genes responsible for global changes in cell
      proliferation, angiogenesis, metastasis, invasion, de-differentiation and energy
      metabolism. Of the three known alpha subunits of HIF transcription factors, HIF
      1alpha and HIF-2alpha have been the most studied. Their differential expression
      and function have been widely discussed, however no clear picture has been drawn
      on how these two transcription factors differently regulate common and unique
      target genes. Their role as oncogenes has also been suggested in several studies.
      In this review we provide an overview of the current knowledge on some of the
      most important aspects of HIFalpha regulation, its role in tumour angiogenesis
      and energetic metabolism. We also give an overview of how the modulation of HIF
      regulating pathways is a potential therapeutic target that may have benefits in
      the treatment of cancer.

PMID- 17525040
TI  - Oxycodone: a pharmacological and clinical review.
AB  - Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and
      delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences
      one hour after administration and lasts for 12 h in the controlled-release
      formulation. Plasma halflife is 3-5 h (half that of morphine) and stable plasma
      levels are reached within 24 h (2-7 days for morphine). Oral bioavailability
      ranges from 60 to 87%, and plasma protein binding is 45%. Most of the drug is
      metabolised in the liver, while the rest is excreted by the kidney along with its
      metabolites. The two main metabolites are oxymorphone--which is also a very
      potent analgesic--and noroxycodone, a weak analgesic. Oxycodone metabolism is
      more predictable than that of morphine, and therefore titration is easier.
      Oxycodone has the same mechanism of action as other opioids: binding to a
      receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and
      decreased excitability. These mechanisms also play a part in the onset of
      dependence and tolerance. The clinical efficacy of oxycodone is similar to that
      of morphine, with a ratio of 1/1.5-2 for the treatment of cancer pain. Long-term
      administration may be associated with less toxicity in comparison with morphine.
      In the future, both opioids could be used simultaneously at low doses to reduce
      toxicity. It does not appear that there are any differences between immediate and
      slow-release oxycodone, except their half-life is 3-4 h, and 12 h, respectively.
      In Spain, controlled-release oxycodone (OxyContin) is marketed as 10-, 20-, 40-
      or 80-mg tablets for b.i.d. administration. Tablets must be taken whole and must
      not be broken, chewed or crushed. There is no food interference. The initial dose
      is 10 mg b.i.d. for new treatments and no dose reduction is needed in the elderly
      or in cases of moderate hepatic or renal failure. Immediate-release oxycodone
      (OxyNorm) is also available in capsules and oral solution. Side effects are those
      common to opioids: mainly nausea, constipation and drowsiness. Vomiting, pruritus
      and dizziness are less common. The intensity of these side effects tends to
      decrease over the course of time. Oxycodone causes somewhat less nausea,
      hallucinations and pruritus than morphine.

PMID- 17525041
TI  - Treatment guidelines in ovarian cancer.
AB  - National and international specialists have met with the aim of writing down the
      guidelines for the treatment of epithelial ovarian cancer (in the Spanish
      Castilian language). These guidelines are based on the International Consensus
      that was published in English in the Annals of Oncology in 2005. This condition
      is the leading cause of death from gynaecological cancer in western countries.
      Its low rate of survival, barely 30% at 5 years, is above all due to late
      diagnosis and inappropriate surgery, so emphasis is put on these aspects. After
      describing the methodology for early detection and a scheme of surgical
      diagnostic procedures in view of the staging of an ovarian mass, the following
      therapeutic strategies will be recommended: cytoreductive surgery together with
      platinum chemotherapy under normal conditions, and also in the case of relapse.
      Likewise, very recent models of treatment focused on molecular targets are
      presented, and a broad section on methodology of clinical assays. As for this, co
      operation among groups is crucial in order to make the conclusions of these
      studies valid for the development of new therapies.

PMID- 17525042
TI  - Biweekly docetaxel and gemcitabine as neoadjuvant chemotherapy followed by
      adjuvant doxorubicin and cyclophosphamide therapy in stage II and III breast
      cancer patients: results of a phase II study.
AB  - INTRODUCTION: The purpose of this phase II study was to evaluate the efficacy and
      safety of neoadjuvant docetaxel/gemcitabine treatment in a biweekly regimen.
      MATERIALS AND METHODS: Patients with stage II/III breast cancer were treated with
      docetaxel (65 mg/m(2)) followed by gemcitabine (2500 mg/m(2)) every 2 weeks for 6
      cycles. Patients with a clinical response or stable disease underwent mastectomy
      or breast-conserving surgery plus axillary dissection. After surgery, patients
      received 4 cycles of standard doxorubicin 60 mg/m(2) and cyclophosphamide 600
      mg/m(2) every 21 days. RESULTS: Thirty-five patients were included in the trial.
      The overall response rate was 71.4% (95% CI: 53.7-85.4), with 8 complete and 17
      partial responses. Breast conservation was possible in 59% of the patients.
      Toxicity was manageable. CONCLUSIONS: We consider biweekly docetaxel and
      gemcitabine could be an active and tolerable regimen option in the neoadjuvant
      setting sequentially with standard adjuvant doxorubicin-cyclophosphamide in
      patients with stage II or III breast cancer.

PMID- 17525043
TI  - Long-term outcome of a phase II study of weekly docetaxel with a short course of
      estramustine and enoxaparine in hormone-resistant prostate cancer patients.
AB  - OBJECTIVE: The objective was to define the toxicity and activity of weekly
      docetaxel administered with a short course of estramustine and enoxaparine in
      patients with hormone-resistant prostate cancer (HRPC). PATIENTS AND METHODS:
      Twenty-four patients were treated with the next regimen: weekly docetaxel 36
      mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg
      three times a day for three consecutive days beginning the day before docetaxel
      (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of
      subcutaneous enoxaparine was administered daily sc on the same days as
      estramustine. Primary endpoints were: toxicity, especially the presence of
      thromboembolic events, PSA response rate and response in measurable disease.
      Secondary endpoints were: time to PSA progression and overall survival. RESULTS:
      Nineteen of 24 patients (79.1%, 95% CI 71-87%) had a PSA response = or >50%. Four
      of the eleven patients with measurable disease had a partial response. The median
      time to PSA progression was 7 months (CI 95%: 6.5-9) and the median survival was
      19 months (IC 95%: 11-24). Toxicity was manageable with no treatment- related
      mortality. Only two patients had grade 4 neutropenia. Two patients had thrombotic
      events, one deep venous thrombosis and one stroke. The main grade 3 non
      haematologic toxicity was diarrhoea and asthenia, both in 25% of patients.
      CONCLUSIONS: Weekly docetaxel with a short course of estramustine and enoxaparine
      is active and tolerable in HRPC patients. The observed incidence of thrombosis
      was lower than previously reported but the association of enoxaparine was not
      enough to completely prevent the thromboembolic events.

PMID- 17525044
TI  - Non-seminomatous germ-cell tumour associated with acute megakaryoblastic
      leukaemia.
AB  - The association of mediastinal germ-cell tumours (MGCTs) with haematologic
      neoplasms is a rare though well known circumstance, and few cases are found in
      the literature. Most of these refer to non-seminomatous tumours in young males.
      The diagnosis of the haematological condition is usually either synchronic or
      metachronic with that of the germ-cell tumour. From those cases that have been
      published, we know that the prognosis is poor and basically determined by the
      haematologic neoplasia. The case report we present is that of a young male with
      an initial diagnosis of both conditions. It was possible to apply specific
      treatment, initially in the case of the leukaemia, and later in the case of the
      germ-cell tumour. The approach adopted is a multidisciplinary one.

PMID- 17525045
TI  - False-positive beta-human chorionic gonadotropin values in the follow-up of
      gestational trophoblastic disease.
AB  - Gestational trophoblastic disease consists of a pathological spectrum of entities
      from molar pregnancies, which are premalignant conditions, to malignant invasive
      choriocarcinoma. Serum Beta-human chorionic gonadotropin (hCG) levels are
      essential both in the diagnosis and in the follow-up. There are high rates of
      complete responses and long-term survivors, because of the excellent
      chemosensitivity of these tumours. After initial management, an increased level
      of Beta-hCG indicates persistent disease. However, in the absence of evidence of
      persistent disease, false-positive Beta-hCG values may be considered. We present
      here the case of a woman with a metastatic choriocarcinoma in complete response
      after chemotherapy, who developed later persistent false-positive values of Beta
      hCG in the follow-up. Causes of false-positive Beta-hCG determinations are
      revised.

PMID- 17525046
TI  - Pathological complete response following docetaxel-based neoadjuvant chemotherapy
      for locally advanced gastric adenocarcinoma.
AB  - Locally advanced gastric adenocarcinoma has a poor outcome. Neoadjuvant treatment
      is being tested in locally advanced non-resectable tumours and in those
      resectable tumours with a high risk of recurrence. Efforts to identify prognostic
      factors and more active and less toxic preoperative regimens are being searched
      for. We report the case of a patient achieving a complete histopathological
      complete response following docetaxel- based neoadjuvant chemotherapy.

PMID- 17525047
TI  - Training models for coronary surgery.
AB  - This paper reviews currently used training models for coronary artery bypass
      grafting (CABG). Training models for CABG are extremely helpful not only for
      training surgical techniques, but also for the evaluation of new technologies and
      for research on bypass graft pathophysiology. Wet-lab models serve as training
      platforms for surgical residents and allow the evaluation of new technology
      (e.g., robotically enhanced CABG). The right coronary artery to left anterior
      descending artery model on the slaughterhouse pig heart is easily available,
      cheap, and effective. In vivo animal models for CABG are much more sophisticated
      and cost intensive. Pigs and dogs are the most commonly used animals for CABG
      training. Offpump CABG techniques, totally endoscopic CABG, endoscopic
      gastroepiploic artery harvesting, and axillocoronary bypass grafting have been
      evaluated in animal models.

PMID- 17525048
TI  - Implantation of CardioWest total artificial heart for irreversible acute
      myocardial infarction shock.
AB  - Patients who develop cardiogenic shock after acute myocardial infarction have a
      very high mortality rate despite early reperfusion therapy. Hemodynamic
      stabilization can often only be achieved by implanting a mechanical circulatory
      support system. When, in cases representing expansive myocardial impairment
      without any chance of recovery, pharmacological therapy and the use of
      percutaneous assist devices have failed, the implantation of a total artificial
      heart is indicated. We report our first experiences with this extensive and
      innovative method of managing irreversible cardiogenic shock patients. The
      CardioWest total artificial heart was implanted in 5 patients (male; mean age, 50
      years). All patients were in irreversible cardiogenic shock despite maximum
      dosages of catecholamines, an intra-aortic balloon pump and/or a femoro-femoral
      bypass. In all patients early reperfusion therapy was performed. After
      implantation of the Cardio West system, all dysfunctional organ systems rapidly
      recovered in all patients. Four of 5 patients underwent successful heart
      transplantation after a mean support time of 156 days. One patient died because
      of enterocolic necroses caused by an embolic event after termination of dicumarol
      therapy. In summary, our first experiences justify this extensive management in
      young patients who would otherwise have died within a few hours.

PMID- 17525049
TI  - Aneurysmal subarachnoid haemorrhage and the anaesthetist.
AB  - The anaesthetist may be involved at various stages in the management of
      subarachnoid haemorrhage (SAH). Thus, familiarity with epidemiological,
      pathophysiological, diagnostic, and therapeutic issues is as important as
      detailed knowledge of the optimal intraoperative anaesthetic management. As the
      prognosis of SAH remains poor, prompt diagnosis and appropriate treatment are
      essential, because early treatment may improve outcome. It is, therefore,
      important to rule out SAH as soon as possible in all patients complaining of
      sudden onset of severe headache lasting for longer than an hour with no
      alternative explanation. The three main predictors of mortality and dependence
      are impaired level of consciousness on admission, advanced age, and a large
      volume of blood on initial cranial computed tomography. The major complications
      of SAH include re-bleeding, cerebral vasospasm leading to immediate and delayed
      cerebral ischaemia, hydrocephalus, cardiopulmonary dysfunction, and electrolyte
      disturbances. Prophylaxis and therapy of cerebral vasospasm include maintenance
      of cerebral perfusion pressure (CPP) and normovolaemia, administration of
      nimodipine, triple-H therapy, balloon angioplasty, and intra-arterial papaverine.
      Occlusion of the aneurysm after SAH is usually attempted surgically ('clipping')
      or endovascularly by detachable coils ('coiling'). The need for an adequate CPP
      (for the prevention of cerebral ischaemia and cerebral vasospasm) must be
      balanced against the need for a low transmural pressure gradient of the aneurysm
      (for the prevention of rupture of the aneurysm). Effective measures to prevent or
      attenuate increases in intracranial pressure, brain swelling, and cerebral
      vasospasm throughout all phases of anaesthesia are prerequisite for optimal
      outcome.

PMID- 17525050
TI  - In vitro interaction of micafungin and fluconazole against Candida.

PMID- 17525051
TI  - Prolonged bacterial exposure to minocycline/rifampicin-impregnated vascular
      catheters does not affect antimicrobial activity of catheters.
AB  - OBJECTIVES: We assessed the in vitro effect of exposing various bacteria to
      minocycline/rifampicin-impregnated vascular catheters on the antimicrobial
      activity of the catheters and the antimicrobial susceptibility of tested
      organisms. METHODS: Segments of minocycline/rifampicin-impregnated catheters were
      placed in agar plates inoculated with methicillin-susceptible Staphylococcus
      aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-resistant
      Staphylococcus epidermidis (MRSE) and vancomycin-resistant Enterococcus (VRE).
      Zones of inhibition were measured at 24 h, and colonies from the edge of this
      zone were retrieved after 72 h and inoculated onto new agar plates. A total of
      seven 72 h cycles were completed. We then measured the MICs of minocycline,
      rifampicin, vancomycin and linezolid for the collected strains. RESULTS: The
      zones of inhibition of the four organisms remained stable after 21 days of
      sequential exposure to the impregnated catheters. The MICs of the antimicrobials
      remained constant, except for the MICs of rifampicin for MRSA and linezolid for
      MRSE, which increased slightly but remained within the susceptible range.
      CONCLUSIONS: Minocycline/rifampicin-impregnated catheters remain effective
      against MSSA, MRSA, MRSE and VRE, as evidenced by stable zones of inhibition
      following 21 day sequential exposure to these catheters. The increase in MIC of
      rifampicin for MRSA may be clinically relevant if the catheter remains in place
      for >12 days though the strain remained susceptible to minocycline, there was no
      concurrent increase in the MIC of other tested drugs, and the zones of inhibition
      remained stable.

PMID- 17525053
TI  - Radiation doses in common X-ray examinations carried out in two dedicated
      paediatric hospitals.
AB  - In this study, the entrance surface dose (ESD) and the respective effective dose
      (E) were determined for paediatric patients undergoing various common
      radiological examinations in two dedicated paediatric hospitals. Measurements of
      ESD were carried out in 289 examinations using thermoluminescent dosemeters. The
      patients were categorised according to their age and the mean ESD and E values
      were determined for each examination and age category. These ESD values were
      compared with the existing diagnostic reference levels (DRLs). In both hospitals
      there were cases where the DRLs were exceeded but in one of them this was rather
      the general rule, since additionally to the routine use of grid and low tube
      potential settings, occasional use of fluoroscopy for positioning check was also
      observed. While the remedial actions required to appropriately reduce the doses
      were clearly identified, this cannot be achieved without the cooperation of
      medical physicists with operators and radiologists.

PMID- 17525052
TI  - Factors influencing caspofungin plasma concentrations in patients of a surgical
      intensive care unit.
AB  - BACKGROUND: Co-morbidity, medical and surgical interventions often cause
      alterations to drug plasma concentrations and pharmacokinetic parameters in
      critically ill patients. In the present study, we investigated parameters
      influencing plasma caspofungin concentrations in patients of a surgical intensive
      care unit (SICU). METHODS: In a monocentre open study, caspofungin trough
      concentrations (C(24)) were determined for a group of SICU patients. A linear
      mixed model was then used to assess factors influencing caspofungin plasma
      concentrations. RESULTS: A total of 40 SICU patients were enrolled. Age and body
      weight ranged from 22 to 76 years and 47 to 108 kg, respectively. All
      participants received a caspofungin loading dose of 70 mg and a maintenance dose
      of 50 mg/day. The median duration of therapy was 10 days. Caspofungin C(24) in
      SICU patients varied more than those determined for healthy subjects reported in
      previous studies (0.52-4.08 microg/mL versus 1.12-1.78 microg/mL). According to
      our model, caspofungin C(24) were predicted to be significantly higher in
      patients with body weight <75 kg (P=0.019) and patients with albumin
      concentration >23.6 g/L (P=0.030). CONCLUSIONS: Our results show that body weight
      and albumin concentration influence caspofungin C(24) in SICU patients and should
      therefore be considered prognostic factors.

PMID- 17525054
TI  - Measurements of neutron dose rates with a balloon in Japan.
AB  - Measurements of cosmic-ray neutron dose rates with a balloon in Sanriku, Japan
      (geographic location: 39 degrees N, 142 degrees E; corresponding geomagnetic
      latitude: 30 degrees N) were conducted at an altitude from 0.2 to 25 km on 25-26
      August 2004 when solar activity was at an average level. Neutron dose rates given
      as ambient dose equivalent rates (H(10)) were measured with high-sensitive
      neutron dose equivalent counters and electronic silicon personal dosimeters
      (EPDs). The neutron dose rates increased with increasing altitude, but they were
      saturated around 15-20 km and decreased with increasing altitude beyond 20 km.
      The neutron ambient dose equivalent rate was 1.5 microSv/h(- 1) at 20 km.
      Measured values were corrected for the deviation of the energy response of the
      dose equivalent counter from the fluence-to-ambient dose equivalent conversion
      coefficient, and the corrected values were very close to the calculated values
      with EPCARD. On the other hand, neutron measurements by the EPDs gave about 10
      times overestimation because of the high sensitivity to cosmic-ray protons.

PMID- 17525055
TI  - Assessment of dose during the life cycle of natural stone production.
AB  - The environmental impact during the life cycle of natural stone production was
      studied. One of the points of interest was radiation. Natural stone samples from
      23 quarries were surveyed for the radioactivity. One quarry was selected for a
      case study where the effective dose to the workers was assessed. The use of these
      stones in buildings was also evaluated with respect to the excess dose caused to
      the residents. According to the results the excess effective dose to the workers
      does not exceed 1 mSv a(-1) at the quarries. In buildings, all natural stones
      studied can be used safely as surfacing materials.

PMID- 17525056
TI  - Assessment of background radioactivity level for Gaziantep region of southeastern
      Turkey.
AB  - This study presents the measurement results of environmental radioactivity levels
      for Gaziantep, an industrial and trade centre in the southeastern part of Turkey.
      The outdoor gamma absorbed dose was measured as 50.1 nGy h(-1), corresponding to
      a total gamma radiation level (of terrestrial and cosmic origin) of 61.5 microSv
      y(-1). The activity concentrations in the surface soil samples collected from the
      study area were determined as 25.2, 23.7 and 289.2 Bq kg(-1) for the natural
      radionuclides (238)U, (232)Th and (40)K, respectively, and 8.02 Bq kg(-1) for the
      fission product (137)Cs. These natural radioactivity sources result in a
      terrestrial gamma level of 46.9 microSv y(-1). The drinking water samples
      collected from the region carry an average of 0.0493 Bq l(-1) of gross alpha and
      0.1284 Bq l(-1) of gross beta activities, which together cause an annual
      effective dose of 1.83 microSv. The measurement results obtained in this study
      indicate that the region has a background radiation level that is within the
      natural limits and shows no significant departure from the other parts of the
      country.

PMID- 17525057
TI  - Indicators for the finger doses in interventional radiology.
AB  - Finger doses and other factors have been recorded in order to investigate
      parameters that could be used to assess the likely level of finger doses of
      interventional radiologists. A relatively good correlation between finger dose
      and dose-area product was found regardless of the type of procedure. The
      correlation between finger dose and screening time was less significant. Very
      significant correlation between finger doses and the personal dosemeter reading
      outside the lead apron was found. This strongly suggests that personal dosemeter
      worn outside the lead apron can serve as a screening device for finger or hand
      doses to the radiologists. For radiologists, surgeons and cardiologists likely to
      receive an annual personal dose reading of more than 20 mSv measured outside the
      lead apron, doses to the hands are likely to be higher than 50 mSv. In these
      cases, monitoring of finger doses is recommended to establish dose levels.

PMID- 17525058
TI  - Evaluation of the characteristics of the neutron reference field using D2O
      moderated 252Cf source.
AB  - The ambient/personal dose equivalent per fluence for D(2)O moderated (252)Cf
      neutron source was determined by measurement. An appropriate subtraction of the
      scattered neutrons is required for the accurate measurement of direct neutrons. A
      cubic shadow object was used for the subtraction of the scattered neutrons from
      the surroundings. The scattered neutrons to be subtracted vary with the position
      of the shadow object due to the large volume of the source. Using the Monte Carlo
      code MCNP-4C, the optimum positions of the shadow object were surveyed for
      subtracting the scattered neutrons. The energy spectra of direct neutrons were
      measured in the optimum position. The dosimetric parameters for the D(2)O
      moderated (252)Cf neutron source were reasonable, taking into account the
      uncertainties of the parameters.

PMID- 17525059
TI  - Calibration of the borated ion chamber at NIST reactor thermal column.
AB  - In boron neutron capture therapy and boron neutron capture enhanced fast neutron
      therapy, the absorbed dose of tissue due to the boron neutron capture reaction is
      difficult to measure directly. This dose can be computed from the measured
      thermal neutron fluence rate and the (10)B concentration at the site of interest.
      A borated tissue-equivalent (TE) ion chamber can be used to directly measure the
      boron dose in a phantom under irradiation by a neutron beam. Fermilab has two
      Exradin 0.5 cm(3) Spokas thimble TE ion chambers, one loaded with boron,
      available for such measurements. At the Fermilab Neutron Therapy Facility, these
      ion chambers are generally used with air as the filling gas. Since alpha
      particles and lithium ions from the (10)B(n,alpha)(7)Li reactions have very short
      ranges in air, the Bragg-Gray principle may not be satisfied for the borated TE
      ion chamber. A calibration method is described in this paper for the
      determination of boron capture dose using paired ion chambers. The two TE ion
      chambers were calibrated in the thermal column of the National Institute of
      Standards and Technology (NIST) research reactor. The borated TE ion chamber is
      loaded with 1,000 ppm of natural boron (184 ppm of (10)B). The NIST thermal
      column has a cadmium ratio of greater than 400 as determined by gold activation.
      The thermal neutron fluence rate during the calibration was determined using a
      NIST fission chamber to an accuracy of 5.1%. The chambers were calibrated at two
      different thermal neutron fluence rates: 5.11 x 10(6) and 4.46 x 10(7)n cm(-2) s(
      1). The non-borated ion chamber reading was used to subtract collected charge not
      due to boron neutron capture reactions. An optically thick lithium slab was used
      to attenuate the thermal neutrons from the neutron beam port so the responses of
      the chambers could be corrected for fast neutrons and gamma rays in the beam. The
      calibration factor of the borated ion chamber was determined to be 1.83 x 10(9)
      +/- 5.5% (+/- 1sigma) n cm(-2) per nC at standard temperature and pressure
      condition.

PMID- 17525060
TI  - Neutron measurements in a Varian 2,100C LINAC facility using a Bonner sphere
      system based on passive gold activation detectors.
AB  - The use of high-energy linear electron accelerators (LINACs) for medical cancer
      treatments is widespread on an international scale. The associated bremsstrahlung
      X rays may produce neutrons as a result of subsequent photonuclear reactions with
      the different materials constituting the accelerator head. The generated neutron
      field is highly variable and depends strongly on the beam energy, on the
      accelerator shielding, on the flattering filter as well as on the movable
      collimators (jaws) design and on the irradiation field geometry. An estimate of
      this photoneutron component is, thus, of practical interest to quantify the
      radiological risk for the working staff and patients. Due to high frequency
      electromagnetic fields, and also to the presence of abundant leaked and scattered
      photons in these installations, measurements of the corresponding neutron fields
      by active dosemeters are extremely difficult. A modified version of the Bonner
      sphere system, based on passive gold activation detectors, has been used to
      perform neutron measurements at two points in a Varian 2,100C LINAC facility. A
      home-made unfolding procedure (CDM) has been utilised to determine the neutron
      spectra present at the measurement points. Results indicate that the giant dipole
      resonance process is the most adequate model to explain neutron production in the
      LINAC and that a thermal component is present at the measurement points.

PMID- 17525061
TI  - Twenty-year follow-up study of radiocesium migration in soil.
AB  - The profile of (137)Cs present in undisturbed soil due to the Chernobyl accident
      was measured repeatedly for approximately 20 y. The vertical migration of (137)Cs
      in soil is a very slow process. The mean vertical migration velocity is estimated
      at approximately 0.1-0.2 cm y(-1). A method based on in situ gamma spectrometry
      measurements and Monte Carlo computations, aimed at estimating the profile of
      (137)Cs without performing any soil sampling, is investigated.

PMID- 17525062
TI  - A comparison of dose savings of lead and lightweight aprons for shielding of 99m
      Technetium radiation.
AB  - Nuclear medicine technologists (NMTs) have the highest effective doses of
      radiation among medical workers. With increase in the use of lightweight
      materials in diagnostic radiography, the aim was to compare the effectiveness of
      lead and lightweight aprons in shielding from 99m-Technetium ((99m)Tc) gamma
      rays. The doses received from a scattering phantom to the entrance, 9cm depth and
      exit of a phantom were measured with LiF:Mg, Cu, P thermoluminescent dosemeters
      (TLDs). Doses and spectra were assessed without no shielding, with 0.5-mm lead
      and lightweight aprons. The lead and lightweight aprons decreased entrance
      surface doses by 76 and 59%, respectively. The spectral analysis showed that the
      lightweight apron provided better dose reduction at energies <95 keV, though lead
      was 35% more efficient at higher energies. While lead apron demonstrated better
      shielding, the additional savings should be considered with the weight
      differential. It is concluded that the lightweight apron is suitable to be worn
      by NMTs interacting with patients injected with a (99m)Tc labelled
      radiopharmaceutical.

PMID- 17525064
TI  - Absorbed dose conversion coefficients for embryo and foetus in neutron fields.
AB  - The Monte Carlo code MCNPX has been used to determine mean absorbed doses to the
      embryo and foetus when the mother is exposed to neutron fields. There are
      situations, such as on-board aircraft, where high-energy neutrons are often
      peaked in top down (TOP) direction. In addition to previous publications for
      standard irradiation geometries, this study provides absorbed dose conversion
      coefficients for the embryo of 8 weeks and the foetus of 3, 6 or 9 months at TOP
      irradiation geometry. The conversion coefficients are compared with the
      coefficients in isotropic irradiation (ISO). With increasing neutron energies,
      the conversion coefficients in TOP irradiation become dominant. A set of
      conversion coefficients is constructed from the higher value in either ISO or TOP
      irradiation at a given neutron energy. In cases where the irradiation geometry is
      not adequately known, this set of conversion coefficients can be used in a
      conservative dose assessment for embryo and foetus in neutron fields.

PMID- 17525063
TI  - Neutron measurements in Spanish nuclear power plants with a Bonner sphere
      spectrometer system.
AB  - Neutron spectrometric measurements with an active Bonner Sphere System (BSS)
      allowed us to determine the reference dosimeter values in Asco I and II and
      Cofrentes (PWR, BWR) Spanish nuclear power plants. Under a request from the
      Spanish National Nuclear Safety Council, the UAB group was in charge of
      characterising the neutron fields at several measurement points (a total of 10)
      inside the containment building of these nuclear installations using an active
      BSS and a home-made MITOM unfolding code. The measurement results in the three
      installations confirm the presence of low-energy neutron components in almost all
      selected points. This developed BSS can be considered as a reference system in
      neutron radiation protection when defining the corresponding protocols for a
      correct personal dosimetry in nuclear power plant installations.

PMID- 17525065
TI  - Microdosimetric characteristics of carbon track-segments.
AB  - Carbon ions were introduced to radiation therapy due to their special physical
      and radiobiological properties. In heavy ion therapy, specification of radiation
      quality is an important issue and rapid calculations are often required for
      treatment planning. Because radiation qualities are closely related to
      microdosimetric spectra and parameters, this study is intended to provide
      microdosimetric parameters of carbon track-segments in the energy range from 50
      MeV to 5 GeV. Monte-Carlo techniques are used to simulate track-segments of
      carbon ions in water. Microdosimetric quantities (the dose mean lineal energies)
      are calculated for the two components of the track-segment: the track-core formed
      by energy deposition of carbon ions and the track-penumbra (an extended region
      around the track-core produced by energy deposition of secondary electrons).

PMID- 17525066
TI  - A phoswich detector for high-energy neutrons.
AB  - A phoswich detector was developed to measure neutron energy spectra from a few
      MeV to a few hundreds MeV in aircrafts and space crafts. Radiation fields, which
      both crafts are exposured, consist of neutrons, gamma rays, protons, etc. The
      phoswich detector can measure neutrons separately from gamma rays and protons.
      The capability of particle discrimination was tested at HIMAC and was found to be
      excellent. Detector response functions to neutrons were simulated with the MCNPX
      code using the measured light outputs of charged particles and were measured with
      quasi-mono-energetic neutrons produced by the p-Li reaction at the NIRS
      cyclotron. Test flight measurements at high altitudes, 6.5 and 8.5 km, were
      performed above the middle part of Japan (cut-off rigidity, 12 GV).

PMID- 17525068
TI  - Effect of laparoscopic ovarian diathermy on circulating inhibin B in women with
      anovulatory polycystic ovary syndrome.

PMID- 17525067
TI  - Induction of prostaglandin E2 production by leukemia inhibitory factor promotes
      migration of first trimester extravillous trophoblast cell line, HTR-8/SVneo.
AB  - BACKGROUND: The invasion of first trimester extravillous trophoblast (EVT) to
      decidua is an important event in placentation. Leukemia inhibitory factor (LIF)
      is an essential factor for mouse implantation, and it is reported that LIF may be
      involved in human first trimester EVT invasion. Prostaglandin E2 (PGE2) is also
      known as a critical factor for first trimester EVT invasion. In this study, we
      investigated the role of LIF in PGE2 production and EVT invasion using a human
      first trimester EVT cell line, HTR-8/SVneo. METHODS AND RESULTS: Co-stimulation
      with LIF and IL-1beta induced higher amounts of PGE2 production and further
      migration of HTR-8/SVneo cells compared with that by stimulation with LIF or IL
      1beta alone. Enhanced PGE2 production was most probably due to the enhanced
      expression of cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1).
      PGE2 produced by HTR-8/SVneo cells promoted the migration of HTR-8/SVneo cells. A
      COX-2 inhibitor suppressed PGE2 production and the migration of HTR-8/SVneo
      cells. Agonists to PGE2 receptors, EP1, EP2 and EP4, promoted the migration of
      HTR-8/SVneo cells. Moreover, stimulation with LIF up-regulated EP1, EP2 and EP4
      expression in HTR-8/SVneo cells. CONCLUSIONS: It is suggested that LIF
      participates in placentation through EVT invasion by up-regulating PGE2
      production and PGE2 receptor expression in first trimester EVT.

PMID- 17525069
TI  - Human chorionic gonadotrophin attenuates NF-kappaB activation and cytokine
      expression of endometriotic stromal cells.
AB  - Recently, a clinical study provided evidence that treatment of endometriotic
      women with human chorionic gonadotrophin (hCG) alleviates disease-related pain
      and sleeplessness suggesting therapeutic effects of the hormone. Since
      endometriosis is associated with aberrant concentrations of inflammatory
      mediators in the peritoneal fluid, we investigated whether hCG may affect
      cytokine-dependent activation of the key-regulatory transcription factor NF
      kappaB and expression of two nuclear factor kappa B (NF-kappaB)-inducible genes,
      tumour necrosing factor (TNF-alpha) and interleukin (IL)-1beta, in stromal cells
      isolated from ectopic endometriotic tissues. Electrophoretic mobility shift assay
      revealed that treatment of these cultures with the urinary preparation hCG-A
      suppressed TNF-alpha- or IL-1beta-induced NF-kappaB DNA-binding activity, whereas
      another urinary hCG preparation (hCG-B) was less effective. Recombinant alphahCG
      or epidermal growth factor (EGF), a contaminant of some urinary hCG preparations,
      did not alter cytokine-dependent NF-kappaB activation. Immunofluorescene of its
      p65 subunit revealed that pre-incubation with hCG-A strongly decreased TNF-alpha
      dependent nuclear expression of NF-kappaB. Accordingly, hCG-A diminished IL-1beta
      induced TNF-alpha transcript levels and protein release measured by quantitative
      real-time PCR and enzyme-linked immunosorbent assay. The hormone also attenuated
      TNF-alpha-dependent mRNA expression of IL-1beta. Western blot analyses revealed
      that hCG-A impaired TNF-alpha-mediated phosphorylation and degradation of the
      inhibitor IkappaBalpha suggesting that the hormone may reduce nuclear import of
      NF-kappaB by stabilizing its inhibitor. The data suggest that hCG attenuates
      inflammation-dependent NF-kappaB activation and cytokine expression that could
      provide one explanation for the beneficial role of the hormone in endometriotic
      patients.

PMID- 17525070
TI  - Commentary: Reliable measurement of the causes of mortality in developing
      countries.

PMID- 17525071
TI  - What is the role of an interdisciplinary researcher?

PMID- 17525072
TI  - Ethnic variation in childhood asthma and wheezing illnesses: findings from the
      Millennium Cohort Study.
AB  - BACKGROUND: It is not clear how respiratory morbidity during early childhood
      varies across ethnic groups in the UK. This article seeks to determine whether
      asthma and wheeze illnesses during early childhood differ across ethnic groups
      and what factors explain observed differences. METHODS: Data from the UK
      Millennium Cohort Study on 14,630 children were analyzed from the second sweep of
      interviews. Parental interviews were conducted when the cohort member was aged
      approximately 3(1/2) years. Data collected included the occurrence of asthma and
      wheezing symptoms, biological and socio-economic factors and markers of cultural
      tradition. RESULTS: At age 3, 12.3% (n = 1,902) of children had ever had asthma
      and 20.0% (n = 3,030) had wheezed in the last 12 months. 18.2% of Black Caribbean
      children and 5.0% of Bangladeshi children reported ever asthma compared with
      11.6% of White children. 25.5% of Black Caribbean children and 8.7% of
      Bangladeshi reported recent wheeze compared with 19.4% of White children. After
      adjustments, the disadvantage in asthma and recent wheeze for Black Caribbeans
      was mostly explained by socio-economic factors (adjusted odds ratios (OR) for
      asthma 1.42, 95% confidence interval (CI) 0.96-2.09; recent wheeze 1.18, 0.85
      1.64). The Bangladeshi advantage lost statistical significance, mostly due to
      adjustment for markers of cultural tradition (adjusted OR for asthma 0.40, 95% CI
      0.15-1.09; recent wheeze 0.44, 0.18-1.19). CONCLUSION: Our results point to the
      need to locate child health within the unique context of each ethnic group and to
      recognize that potential explanations for observed differences do not necessarily
      hold for all groups.

PMID- 17525073
TI  - Molecular analysis of deletions in human chromosome 3p21 and the role of resident
      cancer genes in disease.
AB  - Epithelial cancers inflict a heavy human and social burden. It was estimated
      [Tyczynski JE, Bray F, Parkin DM. Lung cancer in Europe in 2000: epidemiology,
      prevention, and early detection. Lancet Oncol 2003;4:45-55 (Review)] that in
      Europe, in the year 2000, 347 000 persons died of lung cancer alone, the
      deadliest cancer disease. Loss of heterozygosity and large homozygous deletions
      of the human chromosome region 3p21 are especially frequent in epithelial cancers
      of several organs. In fact, 3p21 is a very peculiar region of the genome
      harbouring, tightly clustered, several types of cancer-causing genes (CCG)
      (Lerman MI, Minna JD. The 630 kb lung cancer homozygous deletion region on human
      chromosome 3p21.3: identification and evaluation of the resident candidate tumour
      suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor
      Suppressor Gene Consortium. Cancer Res 2000;60:6116-33). Current results show
      that, unlike it was thought initially, many tumour suppressor genes (TSG) are
      located close by even in small genomic regions. They may be involved, perhaps
      with varying role, in different types of tumour, and may be influenced by the
      genetic background of different human populations as well as by environmental
      pollutants (cigarette smoking, professional exposure). This review will discuss
      methods of molecular analysis of genomic deletions to uncover CCG at 3p21, will
      summarize the present knowledge regarding the TSGs located in this region, and
      will describe a possible model of epithelial cancer pathogenesis.

PMID- 17525074
TI  - Plant parasitic nematode proteins and the host parasite interaction.
AB  - This review focuses on the proteins and secretions of sedentary plant parasitic
      nematodes potentially important for plant-nematode interactions. These nematodes
      are well equipped for parasitism of plants. Having acquired the ability to
      manipulate fundamental aspects of plant biology, they are able to hijack host
      cell development to make their feeding site. They feed exclusively from feeding
      sites as they complete their life cycle, satisfying their nutritional demands for
      development and reproduction. Biochemical and genomic approaches have been used
      successfully to identify a number of nematode parasitism genes. So far, 65 204
      expressed sequence tags (ESTs) have been generated for six Meloidogyne species
      and sequencing projects, currently in progress, will underpin genomic comparisons
      of Meloidogyne spp. with sequences of other pathogens and generate genechip
      microarrays to undertake profiling studies of up- and down-regulated genes during
      the infection process. RNA interference provides a molecular genetic tool to
      study gene function in parasitism. These methods should provide new data to help
      our understanding of how parasitic nematodes infect their hosts, leading to the
      identification of novel pathogenicity genes.

PMID- 17525075
TI  - Identification of aluminium-responsive genes in rice cultivars with different
      aluminium sensitivities.
AB  - Aluminium (Al) toxicity is a worldwide problem in agricultural practice. Based on
      evidence that Al resistance may be an inducible process and that rice is one of
      the most Al-resistant crops, the gene transcriptional responses to Al were
      investigated in two contrasting rice cultivars (resistant XN1 versus sensitive
      XX2) using differential display reverse transcription-PCR (DDRT-PCR) in
      combination with northern blotting analysis. A total of 37 genes were identified
      as differentially expressed, of which five have been previously known as Al
      regulated while the others are novel genes. Among the up-regulated genes, four
      encode ion transporters, two are involved in signal transduction, and five in the
      synthesis of cysteine and metallothionein. These could be members that are
      potentially involved in Al adaptation or resistance. On the other hand, the
      transcription of 17 genes was strongly inhibited under Al stress. These genes are
      associated with cytoskeletal dynamics and metabolism, and could be possible
      targets associated with Al toxicity. All of these differentially expressed genes
      may represent candidates that function in Al responses. The results suggest, at
      the transcriptional level, that cytoskeletal disruption may be associated with Al
      toxicity, whereas ion transport and sulphur metabolism could play major roles in
      Al adaptation or tolerance in rice.

PMID- 17525076
TI  - Localization of myo-inositol phosphate synthase (GmMIPS-1) during the early
      stages of soybean seed development.
AB  - As a precursor to a large variety of compounds, myo-inositol is a central
      molecule required for cell metabolism and plant growth. The de novo synthesis of
      myo-inositol requires the activity of the enzyme D-myo-inositol-3-phosphate
      synthase (MIPS). MIPS cDNAs encoding one or more isoforms have been cloned from a
      number of species, nevertheless, little is known about the regulation of MIPS
      expression in developing seed. Seed-specific expression of a soybean isoform
      (GmMIPS-1) has been demonstrated, but tissue-specific localization during embryo
      development has not been reported. Using immunolocalization techniques, a
      specialized area of GmMIPS-1 expression was identified in the outer integumentary
      layer during early soybean seed development. In addition, localization data
      provided evidence that MIPS was associated with oxalate crystal idioblasts.

PMID- 17525077
TI  - A LEAFY-like gene in the long-day plant, Silene coeli-rosa is dramatically up
      regulated in evoked shoot apical meristems but does not complement the
      Arabidopsis lfy mutant.
AB  - A LEAFY-like gene was cloned in the long-day (LD) plant, Silene coeli-rosa
      (ScLFY). The open reading frame spans 1452 bp encoding a putative protein of 483
      amino acids. Amino acid homology to other LFYs is 43-55%; conserved and variable
      regions were similar to others. However, an intron (808 bp) not found in others
      occurred close to the N-terminal of the C1 domain. Known features of
      transcription factors exhibited by ScLFY were an acidic domain in the central
      variable region, a proline-rich variable-region, and glutamate-rich regions. The
      proximal 5' untranslated region of ScLFY contains an 8 bp motif: CAACGGCC, which
      conforms to the Gibberellic Acid Regulatory Element (GARE), also found in the
      promoter of LFY in Arabidopsis. However, the 5' variable region of ScLFY is
      exceptionally long compared with other LFY genes. ScLFY failed to complement the
      Arabidopsis lfy mutant reflecting the substantial divergence of this gene. ScLFY
      was analysed during inductive and non-inductive treatments using RT-PCR. A clear
      up-regulation of ScLFY occurred in the apical meristem upon evocation of
      flowering, but it was barely detectable in non-inductive conditions. Thus, ScLFY
      is strongly up-regulated in evoked and young floral apices.

PMID- 17525078
TI  - Mutational loss of the prohibitin AtPHB3 results in an extreme constitutive
      ethylene response phenotype coupled with partial loss of ethylene-inducible gene
      expression in Arabidopsis seedlings.
AB  - The eer3-1 loss-of-function mutant, which was identified by screening for
      Arabidopsis mutant seedlings with an enhanced ethylene response, has both
      increased sensitivity and profound exaggeration of response to ethylene when
      visually assessed, yet exhibits partial ethylene insensitivity at the molecular
      level. The eer3-1 mutation represents a conditional allele with an ethylene
      dependent phenotype that results from an amino acid substitution in the
      previously uncharacterized prohibitin, AtPHB3, with complete loss of EER3
      function resulting in an extreme constitutive ethylene response in air.
      Prohibitins in other organisms have diverse roles including transcriptional
      regulation, with loss of prohibitin function in this capacity associated with
      tumour formation in mammals. Subcellular localization of AtPHB3 indicates that it
      is found in several cellular locations, including the nucleus and throughout the
      cytoplasm. Genetic analysis demonstrates that EER3 functions downstream of EIN2,
      since an ein2-5;eer3-2 double mutant has the same profound hypocotyl inhibition
      phenotype seen with the eer3-2 mutant. Based on the presented work, AtPHB3
      probably functions as a positive regulator of expression of a subset of ethylene
      regulated genes along with a group of genes required to maintain growth in the
      presence of ethylene.

PMID- 17525079
TI  - Conformation of cytoskeletal elements during the division of infected Lupinus
      albus L. nodule cells.
AB  - Lupin nodule cells maintain their ability to divide for several cycles after
      being infected by endosymbiotic rhizobia. The conformation of the cytoskeletal
      elements of nodule cells was studied by fluorescence labelling,
      immunocytochemistry, and laser confocal and transmission electron microscopy. The
      dividing infected cells showed the normal microtubule and actin patterns of
      dividing plant cells. The clustered symbiosomes were tethered to the spindle-pole
      regions and moved to the cell poles during spindle elongation. In metaphase,
      anaphase, and early telophase, the symbiosomes were found at opposite cell poles
      where they did not interfere with the spindle filaments or phragmoplast. This
      symbiosome positioning was comparable with that of the organelles (which ensures
      organelle inheritance during plant cell mitosis). Tubulin microtubules and actin
      microfilaments appeared to be in contact with the symbiosomes. The possible
      presence of actin molecular motor myosin in nodules was analysed using a
      monoclonal antibody against the myosin light chain. The antigen was detected in
      protein extracts of nodule and root cytosol as bands of approximately 20 kDa (the
      size expected). In the nodules, an additional polypeptide of 65 kDa was found.
      Immunogold techniques revealed the antigen to be localized over thin
      microfilaments linked to the cell wall, as well as over the thicker microfilament
      bundles and surrounding the symbiosomes. The pattern of cytoskeleton
      rearrangement in dividing infected cells, along with the presence of myosin
      antigen, suggests that the positioning of symbiosomes in lupin nodule cells might
      depend on the same mechanisms used to partition genuine plant cell organelles
      during mitosis.

PMID- 17525080
TI  - Evidence for long-distance xylem transport of signal peptide activity from tomato
      roots.
AB  - Several types of small, endogenous signal peptides are now known to induce a wide
      range of local and systemic responses in plants, but how such signal peptide
      activity is transported over long distances remains unclear. In particular, the
      possible occurrence and root-to-shoot transport of signal peptide activity in the
      xylem does not appear to have been previously investigated. Suspension-cultured
      cells of wild tomato Lycopersicon peruvanium L. were used in an established
      bioassay for detecting nanomolar concentrations of signal peptides via the
      induction of alkalinizing activity. Xylem sap naturally exuded from the cut and
      washed stem-surfaces of de-topped tomato plants (Lycopersicon esculentum L. cv.
      Castlemart) was collected, partially purified, concentrated, and shown by the
      bioassay consistently to contain significant alkalinizing activity. Plant
      salinity treatment induced further small increases in activity. Subsidiary
      experiments indicated that the alkalinizing activity found in the xylem-sap had
      properties similar to those of known plant signal peptides and was root derived.
      Thus, it was (i) detectable within minutes, (ii) eluted similarly during HPLC
      chromatography, (iii) destroyed by incubation with proteases and stable in the
      presence of protease inhibitor cocktail, and (iv) not found in bioassays of
      simulated xylem sap placed on the cut stem-surfaces of non-exuding roots in order
      to detect any significant release of wound peptides from the stem. Further
      investigations of the signal peptide activity in root xylem sap could provide new
      insights into its identity, genes, receptors, origins, and possible hormonal
      roles in regulating shoot growth and development.

PMID- 17525081
TI  - Identification and expression profiling of low oxygen regulated genes from Citrus
      flavedo tissues using RT-PCR differential display.
AB  - The molecular basis for the adaptation of fruit tissues to low oxygen treatments
      remains largely unknown. RT-PCR differential display (DD) was employed to isolate
      anoxic and/or hypoxic genes whose expression responded to short, low-oxygen
      regimes. This approach led to the isolation, cloning, successful sequencing, and
      bioinformatic analysis of 98 transcripts from Citrus flavedo tissues that were
      differentially expressed in DD gels in response to 0, 0.5, 3, and 21% O(2) for 24
      h. RNA blot analysis of 25 DD clones revealed that 11 genes were induced under
      hypoxia and/or anoxia, 11 exhibited constitutive expression and three transcripts
      were suppressed by low oxygen levels. Almost half of the DD cDNAs were either of
      unknown function or shared no apparent homology to any expressed sequences in the
      GenBank/EMBL databases. Six DD genes were similar to molecules of the following
      functions: C-compound and carbohydrate utilization, plant development, amino acid
      metabolism, and biosynthesis of brasinosteroids. Time-course and stress-related
      experiments of low O(2)-regulated genes indicated that these genes responded
      differently in terms of their earliness, band intensity, and their specificity to
      stresses, showing that some of them can be termed hypoxia- or anoxia-induced
      genes.

PMID- 17525082
TI  - Genes associated with opening and senescence of Mirabilis jalapa flowers.
AB  - A modest ethylene climacteric accompanies flower senescence in Mirabilis jalapa
      L., and exogenous ethylene accelerates the process. However, inhibitors of
      ethylene action and synthesis have little effect on the life-span of these
      ephemeral flowers. Treatment with alpha-amanitin, an inhibitor of DNA-dependent
      RNA synthesis, substantially delays the onset of senescence. This effect falls
      linearly between 7 h and 8 h after the start of flower opening. Subtractive
      hybridization was used to isolate transcripts that were up- and down-regulated
      during this critical period. Eighty-two up-regulated and 65 down-regulated
      transcripts were isolated. The genes identified encode homologues of a range of
      transcription factors, and of proteins involved in protein turnover and
      degradation. Real-time quantitative RT-PCR was used to examine expression
      patterns of these genes during flower opening and senescence. Genes that were
      identified as being down-regulated during senescence showed a common pattern of
      very high expression during floral opening. These genes included a homologue of
      CCA1, a 'clock' gene identified in Arabidopsis thaliana and an aspartyl protease.
      Up-regulated genes commonly showed a pattern of increase during the critical
      period (4-9 h after opening), and some showed very strong up-regulation. For
      example, the abundance of transcripts encoding a RING zinc finger protein
      increased >40 000 fold during the critical period.

PMID- 17525083
TI  - The final common pathway of schizophrenia.

PMID- 17525084
TI  - Injections of NGF into neonatal frontal cortex decrease social interaction as
      adults: a rat model of schizophrenia.
AB  - BACKGROUND: Injection of nerve growth factor (NGF) into the developing frontal
      cortex (FC) has been shown to produce adult-onset subcortical dopaminergic
      hyperactivity, impaired prepulse inhibition of the acoustic startle response, and
      several neuropathological features of schizophrenia. The present study was to
      determine whether such lesions would lead to impaired social interaction, a
      prominent negative feature of schizophrenia. METHODS: Rat pups received daily
      injections of human recombinant NGF into the developing FC on postnatal days 1
      and 2 to partially lesion subplate neurons. Lesioned rats were tested in similar
      treatment pairings lasting 23.5 hours using the EthoVision behavioral monitoring
      system at 6 and 14 weeks of age. Brains were then perfusion fixed for
      histological analysis. RESULTS: Lesioned rats showed significantly increased
      movement, relative to controls, during the light phase at 6 weeks of age. At 14
      weeks, they maintained a significantly greater mean distance apart from one
      another, and engaged in significantly less approach and avoidance behavior during
      the dark phase, relative to controls. Histological changes were consistent with
      those described previously in this animal model. CONCLUSION: Results indicate
      that injections of NGF into the developing FC of neonatal rats result in reduced
      social interaction, which is consistent with behaviors observed in human
      schizophrenia patients.

PMID- 17525085
TI  - The association of birth weight with developmental trends in blood pressure from
      childhood through mid-adulthood: the Bogalusa Heart study.
AB  - Low birth weight has been found to be associated with cardiovascular mortality
      and morbidity and with an adverse profile of several cardiovascular risk factors.
      The inverse association between birth weight and blood pressure was consistently
      reported from many populations. Using longitudinal data from the Bogalusa Heart
      Study (Louisiana), the authors investigated the association between birth weight
      and progression of blood pressure through early adulthood, comparing that
      relation between African Americans and Whites. Birth data of 2,275 participants,
      screened two or more times in the Bogalusa Heart Study between 1973 and 2001,
      were retrospectively obtained from birth certificates and were linked to their
      clinical, laboratory, and socioeconomic and lifestyle data in the Bogalusa Heart
      Study data sets. Birth weight was inversely associated with systolic blood
      pressure, diastolic blood pressure, and pulse pressure (p<or=0.01 for all). For
      every 1-kg increase in birth weight, systolic blood pressure dropped by 1.9 mmHg
      (95% confidence interval: -2.6, -1.3), diastolic blood pressure by 0.7 mmHg (95%
      confidence interval: -1.2, -0.2), and pulse pressure by 1.2 mmHg (95% confidence
      interval: -1.7, -0.7). The interaction of birth weight with ethnicity was not
      significant for any outcome. Birth weight was inversely associated with later
      blood pressure. The strength of that association did not differ between African
      Americans and Whites.

PMID- 17525086
TI  - Questioning specialists' attitudes to breast cancer follow-up in primary care.
AB  - BACKGROUND: National Institute for Clinical Excellence (NICE) guidelines
      recommend discharging asymptomatic breast care patients 3 years after diagnosis.
      A role for General Practitioners (GPs) and breast care nurses is proposed,
      together with skills training, but it remains unclear for how long breast cancer
      patients should be followed up, what tests should be done, and who should be
      conducting the follow-up. We therefore surveyed Breast Cancer Specialists.
      DESIGN: A 20-point questionnaire was sent to 562 Specialists registered in the
      Cancer Research Clinical Trials Unit database, with questions on case-load,
      perceptions of follow-up, local policy and opinions on greater primary care
      involvement. RESULTS: The most commonly acknowledged purpose of follow-up was
      detection of treatment-related morbidity. Eighty four percent of respondents
      adhered to a locally developed protocol with only 9% conforming to NICE
      guidelines. The median follow-up was 5 years. Significant factors predicting
      delayed discharge were younger age (P < or = 0.0001); poorer Nottingham
      Prognostic Index (P = 0.003); treatment factors (P = 0.002); and patient risk
      factors (P = 0.003). Centres with higher case-loads (>200/year) were more likely
      to discharge earlier. Reduced workload was perceived as the main benefit of
      discharge, while lack of GP oncological experience and loss of outcome data were
      concerns. CONCLUSIONS: Specialists favour a risk adjusted discharge strategy and
      increased oncology infrastructure in primary care.

PMID- 17525087
TI  - Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide
      regimen in resected gastric cancer patients: a randomized phase III trial by the
      Gruppo Oncologico Italia Meridionale (GOIM 9602 Study).
AB  - BACKGROUND: This randomized, multicenter, phase III trial evaluated the efficacy
      and safety of the combination of epirubicin, leucovorin, 5-fluorouracil and
      etoposide (ELFE regimen) as adjuvant therapy for radically resected gastric
      cancer patients. PATIENTS AND METHODS: From June 1996 to June 2001, 228 stage IB
      IIIB gastric cancer patients were enrolled. All patients received a total or
      subtotal gastrectomy with at least a D1 lymphoadenectomy and were randomly
      assigned to receive surgery alone or surgery followed by chemotherapy. RESULTS: A
      total number of 630 cycles was delivered with a median number of 5. With a median
      follow-up of 60 months, the 5-year overall survival (OS) was 48% in the treatment
      arm and 43.5% in the control arm [hazard ratio (HR) 0.91; 95% confidence interval
      (CI) 0.69-1.21; P = 0.610); the 5-year disease-free survival (DFS) was 44% in the
      treatment arm and 39% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.305).
      In node-positive patients, the 5-year OS was 41% in the treatment arm and 34% in
      the control arm (HR 0.84; 95% CI 0.69-1.01; P = 0.068), while the 5-year DFS was
      39% in the treatment arm and 31% in the control arm (HR 0.88; 95% CI 0.78-0.91; P
      = 0.051). The most common grade 3-4 toxic effects according to World Health
      Organization criteria were hematological and gastrointestinal. CONCLUSIONS: In
      radically resected gastric cancer patients, adjuvant chemotherapy with ELFE
      regimen does not improve OS over surgery alone.

PMID- 17525088
TI  - Peer influence on children's physical activity: an experience sampling study.
AB  - OBJECTIVE: The primary objective was to examine the associations between social
      context (the presence of peers, friends, and family members) and physical
      activity intensity for overweight and lean girls and boys. METHODS: Participants
      for this study included 10 boys (M = 13.4 years; SD = .8) and 10 girls (M = 13.8
      years; SD =. 8). Twelve participants were between the 15th and the 85th BMI
      percentile (eight girls, four boys) and eight youth were at or above the 85th BMI
      percentile (six boys, two girls). Participants reported on their activity
      intensity and whether the activity was solitary or with others for seven
      consecutive days. RESULTS: Children were more likely to report more intense
      physical activity when in the company of peers or close friends. Overweight
      children reported greater physical activity when in the presence of peers than
      did lean children; however, overweight children also reported more time spent
      alone. CONCLUSIONS: Taken together, findings highlight the importance of
      considering peer relationships in studies of physical activity and childhood
      "obesity".

PMID- 17525089
TI  - Clinical impact of genetic aberrations in gastric MALT lymphoma: a comprehensive
      analysis using interphase fluorescence in situ hybridisation.
AB  - BACKGROUND AND AIMS: There is a need for genetic biomarkers to guide prognosis
      and management of gastric mucosa-associated lymphoid tissue (MALT) lymphomas. We
      assessed the incidence and clinical significance of the MALT lymphoma-associated
      genetic abnormalities t(11;18)/API2-MALT1, t(1;14)/BCL10-IGH, t(14;18)/IGH-MALT1,
      t(3;14)/FOXP1-IGH, and extra copies of MALT1 and FOXP1 in gastric MALT lymphomas
      from Japan. METHODS: The presence of translocations and copy number changes
      involving MALT1, IGH and FOXP1 were assessed in 90 cases of gastric MALT lymphoma
      using interphase fluorescence in situ hybridisation (FISH). In cases carrying a
      MALT1 translocation, FISH for API2-MALT1 was performed, whereas in those carrying
      an IGH translocation, FISH was performed for BCL10, BCL6, BCL2, c-MYC and/or
      CCND1. RESULTS: t(11;18)/API2-MALT1 was detected in 18 of 87 (21%) cases and was
      significantly associated with Helicobacter pylori-negativity, resistance to H
      pylori eradication and Bcl10 nuclear expression. Four of 68 (6%) cases carried a
      translocation involving IGH and FOXP1 (n = 1), BCL2 (n = 1) or an unknown partner
      (n = 2). Neither t(1;14)/BCL10-IGH nor t(14;18)/IGH-MALT1 was detected. Extra
      copies of MALT1 and FOXP1 were detected in 18 of 71 (25%) cases and 10 of 59
      (17%) cases, respectively. The presence of extra copies of MALT1 was
      significantly associated with progression or relapse of lymphoma, and was an
      independent adverse prognostic factor for event-free survival as determined by
      multivariate analysis. CONCLUSIONS: t(11;18)/API2-MALT1 is frequent, whereas IGH
      involved translocations are rare in gastric MALT lymphoma in Japan. The presence
      of extra copies of MALT1, often suggestive of partial or complete trisomy 18, is
      a frequent genetic aberration in gastric MALT lymphoma, which appears to predict
      adverse clinical behaviour.

PMID- 17525090
TI  - Intraluminal acid induces oesophageal shortening via capsaicin-sensitive
      neurokinin neurons.
AB  - OBJECTIVE: Intraluminal acid evokes reflex contraction of oesophageal
      longitudinal smooth muscle (LSM) and consequent oesophageal shortening. This
      reflex may play a role in the pathophysiology of oesophageal pain syndromes and
      hiatus hernia formation. The aim of the current study was to elucidate further
      the mechanisms of acid-induced oesophageal shortening. DESIGN: Intraluminal acid
      perfusion of the intact opossum smooth muscle oesophagus was performed in vitro
      in the presence and absence of neural blockade and pharmacological antagonism of
      the neurokinin 2 receptor, while continuously recording changes in oesophageal
      axial length. In addition, the effect of these antagonists on the contractile
      response of LSM strips to the mast cell degranulating agent 48/80 was determined.
      Finally, immunohistochemistry was performed to look for evidence of LSM
      innervation by substance P/calcitonin gene-related peptide (CGRP)-containing
      axons. RESULTS: Intraluminal acid perfusion induced longitudinal axis shortening
      that was completely abolished by capsaicin desensitization, substance P
      desensitization, or the application of the neurokinin 2 receptor antagonist
      MEN10376. Compound 48/80 induced sustained contraction of LSM strips in a
      concentration-dependent fashion and this was associated with evidence of mast
      cell degranulation. The 48/80-induced LSM contraction was antagonized by
      capsaicin desensitization, substance P desensitization and MEN10376, but not
      tetrodotoxin. Immunohistochemistry revealed numerous substance P/CGRP-containing
      neurons innervating the LSM and within the mucosa. CONCLUSIONS: This study
      suggests that luminal acid activates a reflex pathway involving mast cell
      degranulation, activation of capsaicin-sensitive afferent neurons and the release
      of substance P or a related neurokinin, which evokes sustained contraction of the
      oesophageal LSM. This pathway may be a target for treatment of oesophageal pain
      syndromes.

PMID- 17525091
TI  - Missense mutations in pancreatic secretory trypsin inhibitor (SPINK1) cause
      intracellular retention and degradation.
AB  - BACKGROUND/AIMS: Mutations of the SPINK1 gene encoding pancreatic secretory
      trypsin inhibitor have been identified in association with chronic pancreatitis.
      The vast majority of patients carry the N34S variant, whereas other genetic
      variants are relatively rare and their disease association is uncertain. The aim
      of this study was to characterise and compare the functional defects caused by
      the six published missense mutations that affect mature SPINK1-namely, N34S,
      D50E, Y54H, P55S, R65Q, and R67C. METHODS: Wild type and mutant SPINK1 were
      expressed in human embryonic kidney 293T cells via transient transfection. SPINK1
      expression was characterised by RT-PCR, activity assays, and western blots.
      RESULTS: Mutations N34S and P55S did not alter secretion of SPINK1 from HEK 293T
      cells, whereas mutation R65Q decreased secretion about twofold. Remarkably,
      mutations D50E, Y54H, and R67C abolished or markedly diminished secretion, but
      all three mutants were detected in cell extracts, indicating intracellular
      retention and degradation. CONCLUSIONS: The results identify intracellular
      folding defects as a novel mechanism of SPINK1 deficiency associated with chronic
      pancreatitis. The dramatic effects of the D50E and Y54H mutations indicate that
      the interaction between Asp50 and Tyr54 is critical for proper folding of the
      inhibitor. The disease-causing biochemical defect in the N34S mutant is unrelated
      to secretion or trypsin inhibitory activity and remains enigmatic. Finally, the
      patent functional defects in mutants D50E, Y54H, and R67C suggest disease
      association of these rare SPINK variants.

PMID- 17525092
TI  - Long-term prognosis of autoimmune pancreatitis with and without corticosteroid
      treatment.
AB  - OBJECTIVES: Autoimmune pancreatitis (AIP) is a unique form of chronic
      pancreatitis, and has a favourable response to corticosteroid treatment (CST).
      Little is known, however, about the long-term outcome of AIP. This study aimed to
      document the prognosis without and with CST, and to examine the indication for
      CST. PATIENTS AND METHODS: The prognosis and clinical features of 23 patients
      without CST and 19 patients treated with CST from onset were investigated. In
      addition, factors concerning the late occurrence of unfavourable events related
      to AIP were examined. RESULTS: The patients without CST were 19 men and four
      women, with an average age of 66 years. After an average observation period of 25
      months, 16 patients (70%) developed unfavourable events including obstructive
      jaundice as a result of distal bile duct stenosis in four, growing pseudocyst in
      one, sclerogenic changes of extrapancreatic bile duct in nine, hydronephrosis as
      a result of retroperitoneal fibrosis in one, and interstitial nephritis in one.
      Patients with obstructive jaundice at onset showed a higher cumulative event
      occurrence rate (p = 0.025). The patients treated with CST were 16 men and three
      women, with an average age of 64 years. After an average observation period of 23
      months, six patients (32%) developed unfavourable events consisting of
      interstitial pneumonia in three, and a recurrence of obstructive jaundice in
      three. In multivariate analysis, CST (HR 0.33, 95% CI 0.12-0.89, p = 0.029) and
      obstructive jaundice at onset (HR 3.09, 95% CI 1.14-8.32, p = 0.026) were
      significant predictive factors for unfavourable events. CONCLUSION: CST could
      reduce AIP-related unfavourable events. The early introduction of CST is
      recommended especially for patients with obstructive jaundice.

PMID- 17525093
TI  - Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via
      mast cells in normal human colonic biopsies in vitro.
AB  - OBJECTIVE: Persistent stress and life events affect the course of ulcerative
      colitis and irritable bowel syndrome by largely unknown mechanisms. Corticotropin
      releasing hormone (CRH) has been implicated as an important mediator of stress
      induced abnormalities in intestinal mucosal function in animal models, but to
      date no studies in human colon have been reported. The aim was to examine the
      effects of CRH on mucosal barrier function in the human colon and to elucidate
      the mechanisms involved in CRH-induced hyper-permeability. DESIGN: Biopsies from
      39 volunteers were assessed for macromolecular permeability (horseradish
      peroxidase (HRP), (51)Cr-EDTA), and electrophysiology after CRH challenge in
      Ussing chambers. The biopsies were examined by electron and confocal microscopy
      for HRP and CRH receptor localisation, respectively. Moreover, CRH receptor mRNA
      and protein expression were examined in the human mast cell line, HMC-1. RESULTS:
      Mucosal permeability to HRP was increased by CRH (2.8+/-0.5 pmol/cm(2)/h)
      compared to vehicle exposure (1.5+/-0.4 pmol/cm(2)/h), p = 0.032, whereas
      permeability to (51)Cr-EDTA and transmucosal electrical resistance were
      unchanged. The increased permeability to HRP was abolished by alpha-helical CRH
      (9-41) (1.3+/-0.6 pmol/cm(2)/h) and the mast cell stabilizer, lodoxamide (1.6+/
      0.6 pmol/cm(2)/h). Electron microscopy showed transcellular passage of HRP
      through colonocytes. CRH receptor subtypes R1 and R2 were detected in the HMC-1
      cell line and in lamina propria mast cells in human colon. CONCLUSIONS: Our
      results suggest that CRH mediates transcellular uptake of HRP in human colonic
      mucosa via CRH receptor subtypes R1 and R2 on subepithelial mast cells. CRH
      induced macromolecular uptake in human colon mucosa may have implications for
      stress-related intestinal disorders.

PMID- 17525094
TI  - Leukaemia, brain tumours and exposure to extremely low frequency magnetic fields:
      cohort study of Swiss railway employees.
AB  - AIMS: To investigate the relationship between extremely low frequency magnetic
      field (ELF-MF) exposure and mortality from leukaemia and brain tumour in a cohort
      of Swiss railway workers. METHODS: 20,141 Swiss railway employees with 464,129
      person-years of follow-up between 1972 and 2002 were studied. Mortality rates for
      leukaemia and brain tumour of highly exposed train drivers (21 muT average annual
      exposure) were compared with medium and low exposed occupational groups (i.e.
      station masters with an average exposure of 1 muT). In addition, individual
      cumulative exposure was calculated from on-site measurements and modelling of
      past exposures. RESULTS: The hazard ratio (HR) for leukaemia mortality of train
      drivers was 1.43 (95% CI 0.74 to 2.77) compared with station masters. For myeloid
      leukaemia the HR of train drivers was 4.74 (95% CI 1.04 to 21.60) and for
      Hodgkin's disease 3.29 (95% CI 0.69 to 15.63). Lymphoid leukaemia, non-Hodgkin's
      disease and brain tumour mortality were not associated with magnetic field
      exposure. Concordant results were obtained from analyses based on individual
      cumulative exposure. CONCLUSIONS: Some evidence of an exposure-response
      association was found for myeloid leukaemia and Hodgkin's disease, but not for
      other haematopoietic and lymphatic malignancies and brain tumours.

PMID- 17525095
TI  - Drinking social norms and drinking behaviours: a multilevel analysis of 137
      workgroups in 16 worksites.
AB  - BACKGROUND: Previous studies on worksite drinking norms showed individually
      perceived norms were associated with drinking behaviours. OBJECTIVE: To examine
      whether restrictive drinking social norms shared by workgroup membership are
      associated with decreased heavy drinking, frequent drinking and drinking at work
      at the worker level. METHODS: The sample included 5338 workers with complete data
      nested in 137 supervisory workgroups from 16 American worksites. Multilevel
      models were fitted to examine the association between workgroup drinking norms
      and heavy drinking, frequent drinking and drinking at work. RESULTS: Multivariate
      adjusted models showed participants working in workgroups in the most
      discouraging drinking norms quartile were 45% less likely to be heavy drinkers,
      54% less likely to be frequent drinkers and 69% less likely to drink at work than
      their counterparts in the most encouraging quartile. CONCLUSIONS: Strong
      associations between workgroup level restrictive drinking social norms and
      drinking outcomes suggest public health efforts at reducing drinking and alcohol
      related injuries, illnesses and diseases should target social interventions at
      worksites.

PMID- 17525097
TI  - Validation of the NARCOMS registry: diagnosis.
AB  - The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is
      a patient registry, wherein the diagnoses of multiple sclerosis (MS) are
      unverified. We compared self-reported diagnoses of registry participants to
      physician-reported diagnoses, and with diagnoses based on medical records review.
      Registry participants with more than one of the following: age of onset <10 or
      >50 years, no bladder symptoms or fatigue, or zero or more than four relapses in
      the last year, were considered atypical. All others were considered typical. We
      sent letters to participants describing the study, surveyed treating physicians
      regarding the participants' diagnosis, and reviewed medical records. Diagnosis
      was classified by the McDonald and Poser criteria. Of the 240 participants
      sampled, 109 were in active registry status with accurate contact information. Of
      these, 52 consented, 29 refused and 28 did not respond (weighted response rate
      76.3+/-4.5%). Some 37 of 38 physician surveys confirmed the diagnosis of MS
      (98.8+/-1.2%). After reviewing 41 medical records, we classified 53.2+/-8.9% of
      participants as definite MS, 16.9+/-6.8% as possible MS, while the remainder had
      insufficient data for diagnostic confirmation. We confirmed a diagnosis of MS in
      98.7+/-1.3% of participants based on records review, physician survey or
      telephone interview, supporting the validity of the diagnoses reported by NARCOMS
      participants.

PMID- 17525096
TI  - Occupational risk factors in Alzheimer's disease: a review assessing the quality
      of published epidemiological studies.
AB  - Epidemiological evidence of an association between Alzheimer's disease (AD) and
      the most frequently studied occupational exposures--pesticides, solvents,
      electromagnetic fields (EMF), lead and aluminium--is inconsistent.
      Epidemiological studies published up to June of 2003 were systematically searched
      through PubMed and Toxline. Twenty-four studies (21 case-control and 3 cohort
      studies) were included. Median GQI was 36.6% (range 19.5-62.9%). Most of the case
      control studies had a GQI of <50%. The study with the highest score was a cohort
      study. Likelihood of exposure misclassification bias affected 18 of the 24
      studies. Opportunity for bias arising from the use of surrogate informants
      affected 17 studies, followed by disease misclassification (11 studies) and
      selection bias (10 studies). Eleven studies explored the relationship of AD with
      solvents, seven with EMF, six with pesticides, six with lead and three with
      aluminium. For pesticides, studies of greater quality and prospective design
      found increased and statistically significant associations. For the remaining
      occupational agents, the evidence of association is less consistent (for solvents
      and EMF) or absent (for lead and aluminium).

PMID- 17525098
TI  - Rhizobitoxine-induced chlorosis occurs in coincidence with methionine deficiency
      in soybeans.
AB  - BACKGROUND AND AIMS: Rhizobitoxine, produced by the legume symbiont
      Bradyrhizobium elkanii, inhibits cystathionine-beta-lyase (EC 4.4.1.8) in
      methionine biosynthesis and 1-aminocyclopropane-1-carboxylate synthase (ACC) in
      ethylene biosynthesis. Rhizobitoxine production by B. elkanii enhances nodulation
      of host legumes via the inhibition of ethylene synthesis, but causes foliar
      chlorosis in susceptible soybeans, though how it does so remains to be
      investigated. The aim of this study was to examine the physiological basis of
      rhizobitoxine-induced chlorosis in soybeans. METHODS: Wild-type B. elkanii and a
      rhizobitoxine-deficient mutant were inoculated in Glycine max 'Lee'. Thirty days
      after inoculation, the upper parts of soybean shoots were analysed for amino acid
      contents. Chlorotic soybeans inoculated with wild-type B. elkanii were treated
      with methionine and ACC to assess the effects of the chemicals on the chlorosis.
      KEY RESULTS: Chlorotic upper shoots of soybeans inoculated with wild-type B.
      elkanii had a lower methionine content and higher accumulation of the methionine
      precursors than those with the rhizobitoxine-deficient mutant. In addition, the
      foliar chlorosis was alleviated by the application of methionine. CONCLUSIONS:
      Rhizobitoxine-induced chlorosis occurs in coincidence with methionine deficiency
      as a result of cystathione-beta-lyase inhibition during methionine biosynthesis.

PMID- 17525099
TI  - Extraordinarily high leaf selenium to sulfur ratios define 'Se-accumulator'
      plants.
AB  - BACKGROUND AND AIMS: Selenium (Se) and sulfur (S) exhibit similar chemical
      properties. In flowering plants (angiosperms) selenate and sulfate are acquired
      and assimilated by common transport and metabolic pathways. It is hypothesized
      that most angiosperm species show little or no discrimination in the accumulation
      of Se and S in leaves when their roots are supplied a mixture of selenate and
      sulfate, but some, termed Se-accumulator plants, selectively accumulate Se in
      preference to S under these conditions. METHODS: This paper surveys Se and S
      accumulation in leaves of 39 angiosperm species, chosen to represent the range of
      plant Se accumulation phenotypes, grown hydroponically under identical
      conditions. RESULTS: The data show that, when supplied a mixture of selenate and
      sulfate: (1) plant species differ in both their leaf Se ([Se](leaf)) and leaf S
      ([S](leaf)) concentrations; (2) most angiosperms show little discrimination for
      the accumulation of Se and S in their leaves and, in non-accumulator plants,
      [Se](leaf) and [S](leaf) are highly correlated; (3) [Se](leaf) in Se-accumulator
      plants is significantly greater than in other angiosperms, but [S](leaf),
      although high, is within the range expected for angiosperms in general; and (4)
      the Se/S quotient in leaves of Se-accumulator plants is significantly higher than
      in leaves of other angiosperms. CONCLUSION: The traits of extraordinarily high
      [Se](leaf) and leaf Se/S quotients define the distinct elemental composition of
      Se-accumulator plants.

PMID- 17525100
TI  - Large clones on cliff faces: expanding by rhizomes through crevices.
AB  - BACKGROUND AND AIMS: Large clones of rhizomatous plants are found in many
      habitats, but little is known about whether such clones also occur on cliff faces
      where environmental conditions are extremely harsh and heterogeneous. METHODS:
      Using molecular (intersimple sequence repeat, ISSR) markers, the genotypic
      composition of a cliff-face population of Oxyria sinensis in Sichuan, China, was
      investigated. KEY RESULTS: The 98 O. sinensis ramets sampled belonged to 12
      different genotypes (clones). The three most frequent clones were represented
      with 45, 22 and 12 ramets, respectively; the remaining nine were represented with
      only one to five ramets. The three largest clones spanned at least 2.7 m in the
      vertical direction and 4.6-6.9 m in the horizontal direction on the cliff face.
      CONCLUSIONS: On the cliff face, large clones of O. sinensis are formed by
      rhizomes growing along the crevices. Expansion by rhizomes may help O. sinensis
      to exploit the patchy resources and support establishment and growth of new
      ramets. Moreover, rooted ramets connected by rhizomes may effectively reduce the
      susceptibility of O. sinensis to rock fall and erosion and thus greatly improve
      the chances for long-term survival. The multi-clone structure indicates that
      sexual reproduction is also important for the long-term persistence of O.
      sinensis populations on cliffs.

PMID- 17525101
TI  - Diphtheria toxin mutant CRM197 possesses weak EF2-ADP-ribosyl activity that
      potentiates its anti-tumorigenic activity.
AB  - CRM197, a mutated diphtheria toxin (DT), has long been recognized to be a non
      toxic protein. Based on its non-toxic feature, this protein has been utilized for
      various purposes, including as an inhibitor of heparin-binding EGF-like growth
      factor (HB-EGF) and as an immunological adjuvant for vaccination. Here we show
      evidence that CRM197 has a weak toxicity. This toxicity was observed in cells
      over-expressing the DT receptor/proHB-EGF, but not in parental cells, indicating
      that the toxicity was mediated through DT receptor. CRM197 did not show any
      toxicity toward DT-resistant cells, which have a mutation in elongation factor 2,
      and a cell-free assay revealed the existence of weak EF-2-ADP ribosylation
      activity in fragment A of CRM197. Thus, the present study indicates a requirement
      for specific care in the use of CRM197 at a high dosage, although the toxicity of
      CRM197 is about 10(6) times less than that of wild-type DT. We found that a
      monoclonal antibody to DT inhibited CRM197 toxicity, but did not affect the
      inhibitory activity of CRM197 toward HB-EGF-induced mitogenic activity. CRM197
      strongly inhibits tumour growth in nude mice. The anti-DT monoclonal antibody
      administered with CRM197 reduced the anti- tumourigenic effect of CRM197,
      indicating that the toxicity of CRM197 potentiates its anti- tumourigenic effect.

PMID- 17525102
TI  - Molecular determinants of substrate recognition in thermostable alpha
      glucosidases belonging to glycoside hydrolase family 13.
AB  - Bacillus stearothermophilus alpha-1,4-glucosidase (BS) is highly specific for
      alpha-1,4-glucosidic bonds of maltose, maltooligosaccharides and alpha-glucans.
      Bacillus thermoglucosdasius oligo-1,6-glucosidase (BT) can specifically hydrolyse
      alpha-1,6 bonds of isomaltose, isomaltooligosaccharides and alpha-limit dextrin.
      The two enzymes have high homology in primary structure and belong to glycoside
      hydrolase family 13, which contain four conservative regions (I, II, III and IV).
      The two enzymes are suggested to be very close in structure, even though there
      are strict differences in their substrate specificities. Molecular determinants
      of substrate recognition in these two enzymes were analysed by site-directed
      mutagenesis. Twenty BT-based mutants and three BS-based mutants were constructed
      and characterized. Double substitutions in BT of Val200 -->Ala in region II and
      Pro258 -->Asn in region III caused an appearance of maltase activity compared
      with BS, and a large reduction of isomaltase activity. The values of k(0)/K(m)
      (s(-1). mM(-1)) of the BT-mutant for maltose and isomaltose were 69.0 and 15.4,
      respectively. We conclude that the Val/Ala200 and Pro/Asn258 residues in the
      alpha-glucosidases may be largely responsible for substrate recognition, although
      the regions I and IV also exert a slight influence. Additionally, BT V200A and
      V200A/P258N possessed high hydrolase activity towards sucrose.

PMID- 17525103
TI  - Errors in a stat laboratory: types and frequencies 10 years later.
AB  - BACKGROUND: In view of increasing attention focused on patient safety and the
      need to reduce laboratory errors, it is important that clinical laboratories
      collect statistics on error occurrence rates over the whole testing cycle,
      including pre-, intra-, and postanalytical phases. METHODS: The present study was
      conducted in 2006 according to the design we previously used in 1996 to monitor
      the error rates for laboratory testing in 4 different departments (internal
      medicine, nephrology, surgery, and intensive care). For 3 months, physicians and
      nurses were asked to pay careful attention to all test results. Any suspected
      laboratory error was recorded with associated pertinent clinical information.
      Every day, a laboratory physician visited the 4 departments and a critical
      appraisal was made of any suspect results. RESULTS: Among a total of 51 746
      analyses, clinicians notified us of 393 questionable findings, 160 of which were
      confirmed as laboratory errors. The overall frequency of errors, 3092 ppm, was
      significantly lower (P <0.05) than in 1996 (4700 ppm). Of the 160 confirmed
      errors, 61.9% were preanalytical errors, 15% were analytical, and 23.1% were
      postanalytical. CONCLUSIONS: During the last decade the error rates in our stat
      laboratory have been reduced significantly. As demonstrated by the distribution
      pattern, the pre- and postanalytical steps still have the highest error
      prevalences, but changes have occurred in the types and frequencies of errors in
      these phases of testing.

PMID- 17525105
TI  - Optimization of high-resolution melting analysis for low-cost and rapid screening
      of allelic variants of Bacillus anthracis by multiple-locus variable-number
      tandem repeat analysis.
AB  - BACKGROUND: Molecular genotyping of Bacillus anthracis, the etiologic agent of
      anthrax, is important for differentiating and identifying strains from different
      geographic areas and for tracing strains deliberately released in a bioterrorism
      attack. We previously described a multiple-locus variable-number tandem repeat
      (VNTR) analysis (MLVA) based on 25 marker loci. Although the method has great
      differentiating power and reproducibility, faster genotyping at low cost may be
      requested to accurately identify B. anthracis strains in the field. METHODS: We
      used the High Resolution Melter-1 (Idaho Technology) and a saturating dye of
      double-stranded DNA (LCGreen I) to identify alleles via PCR and melting-curve
      analysis of the amplicons. We applied high-resolution melting analysis (HRMA) to
      a collection of 19 B. anthracis strains. RESULTS: HRMA produced reproducible
      results for 6 of the 25 B. anthracis loci tested. These easily interpretable and
      distinguishable melting curve results were consistent with MLVA results obtained
      for the same alleles. The feasibility of this method was demonstrated in testing
      of different allelic variants for the 6 selected loci. CONCLUSIONS: The described
      HRMA application for screening B. anthracis VNTR loci is fast and widely
      accessible and may prove particularly useful under field conditions.

PMID- 17525104
TI  - Increased serum lipoprotein(a) concentrations and low molecular weight phenotypes
      of apolipoprotein(a) are associated with symptomatic peripheral arterial disease.
AB  - BACKGROUND: Increased concentrations of lipoprotein(a) [Lp(a)] have been
      considered a genetically determined risk factor for coronary artery and
      cerebrovascular disease. Only 2 small and conflicting studies have investigated
      the possibility of an association of peripheral arterial disease (PAD) with high
      serum Lp(a) concentrations and low molecular weight (LMW) phenotypes of
      apolipoprotein(a) [apo(a)]. METHODS: We measured serum concentrations of Lp(a)
      and apo(a) phenotypes in 213 patients with symptomatic PAD and 213 controls
      matched for sex, age (within 2 years), and presence of diabetes. RESULTS:
      Patients with PAD showed significantly higher median serum concentrations of
      Lp(a) (76 vs 47 mg/L; P = 0.003) and a higher frequency of LMW apo(a) phenotypes
      (41% vs 26%; P = 0.002) than controls. After adjustment for several potential
      confounders, increased Lp(a) concentrations (>195 mg/L, i.e., 75th percentile of
      the entire study sample) and LMW apo(a) phenotypes were significant predictors of
      PAD, with odds ratios of 3.73 (95% CI 2.08-6.67; P <0.001) and 2.21 (95% CI 1.33
      3.67; P = 0.002), respectively. CONCLUSIONS: In this study sample, both increased
      serum concentrations of Lp(a) and the presence of LMW apo(a) phenotypes were
      associated with the presence of symptomatic PAD independent of traditional and
      nontraditional cardiovascular risk factors. Because PAD is considered an
      indicator of systemic atherosclerotic disease, our results suggest a possible
      role of Lp(a) as a genetically determined marker for systemic atherosclerosis.

PMID- 17525106
TI  - Identifying common genetic variants by high-resolution melting.
AB  - BACKGROUND: Heteroduplex scanning techniques usually detect all heterozygotes,
      including common variants not of clinical interest. METHODS: We conducted high
      resolution melting analysis on the 24 exons of the ACVRL1 and ENG genes
      implicated in hereditary hemorrhagic telangiectasia (HHT). DNA in samples from 13
      controls and 19 patients was PCR amplified in the presence of LCGreen I, and all
      768 exons melted in an HR-1 instrument. We used 10 wild-type controls to identify
      common variants, and the remaining samples were blinded, amplified, and analyzed
      by melting curve normalization and overlay. Unlabeled probes characterized the
      sequence of common variants. RESULTS: Eleven common variants were associated with
      8 of the 24 HHT exons, and 96% of normal samples contained at least 1 variant. As
      a result, the positive predictive value (PPV) of a heterozygous exon was low
      (31%), even in a population of predominantly HHT patients. However, all common
      variants produced unique amplicon melting curves that, when considered and
      eliminated, resulted in a PPV of 100%. In our blinded study, 3 of 19 heterozygous
      disease-causing variants were missed; however, 2 were clerical errors, and the
      remaining false negative would have been identified by difference analysis.
      CONCLUSIONS: High-resolution melting analysis is a highly accurate heteroduplex
      scanning technique. With many exons, however, use of single-sample instruments
      may lead to clerical errors, and routine use of difference analysis is
      recommended. Common variants can be identified by their melting curve profiles
      and genotyped with unlabeled probes, greatly reducing the false-positive results
      common with scanning techniques.

PMID- 17525107
TI  - Agreement in breast cancer classification between microarray and quantitative
      reverse transcription PCR from fresh-frozen and formalin-fixed, paraffin-embedded
      tissues.
AB  - BACKGROUND: Microarray studies have identified different molecular subtypes of
      breast cancer with prognostic significance. To transition these classifications
      into the clinical laboratory, we have developed a real-time quantitative reverse
      transcription (qRT)-PCR assay to diagnose the biological subtypes of breast
      cancer from fresh-frozen (FF) and formalin-fixed, paraffin-embedded (FFPE)
      tissues. METHODS: We used microarray data from 124 breast samples as a training
      set for classifying tumors into 4 previously defined molecular subtypes: Luminal,
      HER2(+)/ER(-), basal-like, and normal-like. We used the training set data in 2
      different centroid-based algorithms to predict sample class on 35 breast tumors
      (test set) procured as FF and FFPE tissues (70 samples). We classified samples on
      the basis of large and minimized gene sets. We used the minimized gene set in a
      real-time qRT-PCR assay to predict sample subtype from the FF and FFPE tissues.
      We evaluated primer set performance between procurement methods by use of several
      measures of agreement. RESULTS: The centroid-based algorithms were in complete
      agreement in classification from FFPE tissues by use of qRT-PCR and the minimized
      "intrinsic" gene set (40 classifiers). There was 94% (33 of 35) concordance
      between the diagnostic algorithms when comparing subtype classification from FF
      tissue by use of microarray (large and minimized gene set) and qRT-PCR data. We
      found that the ratio of the diagonal SD to the dynamic range was the best method
      for assessing agreement on a gene-by-gene basis. CONCLUSIONS: Centroid-based
      algorithms are robust classifiers for breast cancer subtype assignment across
      platforms and procurement conditions.

PMID- 17525108
TI  - Optimal markers for real-time quantitative reverse transcription PCR detection of
      circulating tumor cells from melanoma, breast, colon, esophageal, head and neck,
      and lung cancers.
AB  - BACKGROUND: The detection of circulating tumor cells (CTCs) may prove useful for
      screening, prognostication, and monitoring of response to therapy. However, given
      the large background of circulating cells, it is probably necessary to detect 1
      cancer cell in >10(6) leukocytes. Although reverse transcription (RT)-PCR is
      potentially sensitive and specific enough to achieve this goal, success will
      require the use of appropriate mRNA markers. The goal of this study was to
      identify optimal marker combinations for detection of CTCs. METHODS: An extensive
      literature and internet database survey was conducted to identify potential
      markers. We then used real-time quantitative RT-PCR to test for expression of
      selected potential markers in tissue samples from primary tumors of breast,
      colon, esophagus, head and neck, lung, and melanoma and normal blood samples.
      Markers with high expression in tumors and a median 1000-fold lower expression in
      normal blood were considered potentially useful for CTC detection and were tested
      further in an expanded sample set. RESULTS: A total of 52 potential markers were
      screened, and 3-8 potentially useful markers were identified for each tumor type.
      The mRNAs for all but 2 markers were found in normal blood. Marker combinations
      were identified for each tumor type that had a minimum 1000-fold higher
      expression in tumors than in normal blood. CONCLUSIONS: Several mRNA markers may
      be useful for RT-PCR-based detection of CTCs from each of 6 cancer types.
      Quantification of these mRNAs is essential to distinguish normal expression in
      blood from that due to the presence of CTCs. Few markers provide adequate
      sensitivity individually, but combinations of markers may produce good
      sensitivity for detection of the presence of these 6 neoplasms.

PMID- 17525109
TI  - Setting up for the block: the mechanism underlying lidocaine's use-dependent
      inhibition of sodium channels.

PMID- 17525110
TI  - NKCC1: tales from the dark side of the crypt.

PMID- 17525111
TI  - Tropomyosin in the groove? Molecular insights into an inherited myopathy.

PMID- 17525112
TI  - Resurgent Na+ current in pyramidal neurones of rat perirhinal cortex: axonal
      location of channels and contribution to depolarizing drive during repetitive
      firing.
AB  - The perirhinal cortex (PRC) is a supra-modal cortical area that collects and
      integrates information originating from uni- and multi-modal neocortical regions
      and directed to the hippocampus. The mechanisms that underlie the specific
      excitable properties of the different PRC neuronal types are still largely
      unknown, and their elucidation may be important in understanding the integrative
      functions of PRC. In this study we investigated the expression and properties of
      resurgent Na(+) current (I(NaR)) in pyramidal neurones of rat PRC area 35 (layer
      II). Patch-clamp experiments in acute PRC slices were first carried out. A
      measurable I(NaR) was expressed by a large majority of neurones (31 out of 35
      cells). I(NaR) appeared as an inward, slowly decaying current elicited upon step
      repolarization after depolarizations sufficient to induce nearly complete
      inactivation of the transient Na(+) current (I(NaT)). I(NaR) had a peak amplitude
      of approximately 2.5% that of I(NaT), and showed the typical biophysical
      properties also observed in other neuronal types (i.e. cerebellar Purkinje and
      granule cells), including a bell-shaped current-voltage relationship with a peak
      at approximately -40 mV, and a characteristic acceleration of activation and
      decay speed at potentials negative to -45 mV. Current-clamp experiments were then
      carried out in which repetitive action-potential discharge at various frequencies
      was induced with depolarizing current injection. The voltage signals thus
      obtained were then used as command waveforms for voltage-clamp recordings. These
      experiments showed that a Na(+) current identifiable as I(NaR) activates in the
      early interspike phase even at relatively high firing frequencies (20 Hz),
      thereby contributing to the depolarizing drive and possibly enhancing repetitive
      discharge. In acutely dissociated area 35 layer II neurones, as well as in
      nucleated patches from the same neurones, I(NaR) was never observed, despite the
      presence of typical I(NaT)s. Since in both preparations neuronal processes are
      lost, we carried out experiments of focal tetrodotoxin (TTX) application in
      slices to verify whether the channels responsible for I(NaR) are located in
      compartment(s) different from the soma. We found that TTX preferentially
      inhibited I(NaR) when applied close to the site of axon emergence from soma,
      whereas application to the apical pole of the soma had a significantly smaller
      effect on I(NaR). Our results indicate that in area 35 pyramidal cells I(NaR) is
      largely generated in the axon initial segment, where it may participate in
      setting the coding properties of these neurones.

PMID- 17525113
TI  - Membrane cholesterol modulates Kv1.5 potassium channel distribution and function
      in rat cardiomyocytes.
AB  - Membrane lipid composition is a major determinant of cell excitability. In this
      study, we assessed the role of membrane cholesterol composition in the
      distribution and function of Kv1.5-based channels in rat cardiac membranes. In
      isolated rat atrial myocytes, the application of methyl-beta-cyclodextrin (MCD),
      an agent that depletes membrane cholesterol, caused a delayed increase in the
      Kv1.5-based sustained component, I(kur), which reached steady state in
      approximately 7 min. This effect was prevented by preloading the MCD with
      cholesterol. MCD-increased current was inhibited by low 4-aminopyridine
      concentration. Neonatal rat cardiomyocytes transfected with Green Fluorescent
      Protein (GFP)-tagged Kv1.5 channels showed a large ultrarapid delayed-rectifier
      current (I(Kur)), which was also stimulated by MCD. In atrial cryosections, Kv1.5
      channels were mainly located at the intercalated disc, whereas caveolin-3
      predominated at the cell periphery. A small portion of Kv1.5 floated in the low
      density fractions of step sucrose-gradient preparations. In live neonatal
      cardiomyocytes, GFP-tagged Kv1.5 channels were predominantly organized in
      clusters at the basal plasma membrane. MCD caused reorganization of Kv1.5
      subunits into larger clusters that redistributed throughout the plasma membrane.
      The MCD effect on clusters was sizable 7 min after its application. We conclude
      that Kv1.5 subunits are concentrated in cholesterol-enriched membrane
      microdomains distinct from caveolae, and that redistribution of Kv1.5 subunits by
      depletion of membrane cholesterol increases their current-carrying capacity.

PMID- 17525114
TI  - The main source of ambient GABA responsible for tonic inhibition in the mouse
      hippocampus.
AB  - The extracellular space of the brain contains gamma-aminobutyric acid (GABA) that
      activates extrasynaptic GABA(A) receptors mediating tonic inhibition. The source
      of this GABA is uncertain: it could be overspill of vesicular release, non
      vesicular leakage, reverse transport, dying cells or glia. Using a novel
      approach, we simultaneously measured phasic and tonic inhibitory currents and
      assessed their correlation. Enhancing or diminishing vesicular GABA release in
      hippocampal neurons caused highly correlated changes in the two inhibitions.
      During high-frequency phasic inhibitory bursts, tonic current was also enhanced
      as shown by simulating the summation of IPSCs and by recordings in knockout mice
      devoid of tonic inhibitory current. When vesicular release was reduced by
      blocking action potentials or the vesicular GABA transporter, phasic and tonic
      currents decreased in a correlated fashion. Our results are consistent with most
      of hippocampal tonic inhibitory current being mediated by GABA released from the
      very vesicles responsible for activating phasic inhibition.

PMID- 17525115
TI  - Functional role of A-type potassium currents in rat presympathetic PVN neurones.
AB  - Despite the fact that paraventricular nucleus (PVN) neurones innervating the
      rostral ventrolateral medulla (RVLM) play important roles in the control of
      sympathetic function both in physiological and pathological conditions, the
      precise mechanisms controlling their activity are still incompletely understood.
      In the present study, we evaluated whether the transient outward potassium
      current I(A) is expressed in PVN-RVLM neurones, characterized its biophysical and
      pharmacological properties, and determined its role in shaping action potentials
      and firing discharge in these neurones. Patch-clamp recordings obtained from
      retrogradely labelled, PVN-RVLM neurones indicate that a 4-AP sensitive, TEA
      insensitive current, with biophysical properties consistent with I(A), is present
      in these neurones. Pharmacological blockade of I(A) depolarized resting V(m) and
      prolonged Na(+) action potential duration, by increasing its width and by slowing
      down its decay time course. Interestingly, blockade of I(A) either increased or
      decreased the firing activity of PVN-RVLM neurones, supporting the presence of
      subsets of PVN-RVLM neurones differentially modulated by I(A). In all cases, the
      effects of I(A) on firing activity were prevented by a broad spectrum Ca(2+)
      channel blocker. Immunohistochemical studies suggest that I(A) in PVN-RVLM
      neurons is mediated by Kv1.4 and/or Kv4.3 channel subunits. Overall, our results
      demonstrate the presence of I(A) in PVN-RVLM neurones, which actively modulates
      their action potential waveform and firing activity. These studies support I(A)
      as an important intrinsic mechanism controlling neuronal excitability in this
      central presympathetic neuronal population.

PMID- 17525116
TI  - Optical imaging of Ca2+-evoked fluid secretion by murine nasal submucosal gland
      serous acinar cells.
AB  - Airway submucosal glands are sites of high expression of the cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl(-) channel and contribute to fluid
      homeostasis in the lung. However, the molecular mechanisms of gland ion and fluid
      transport are poorly defined. Here, submucosal gland serous acinar cells were
      isolated from murine airway, identified by immunofluorescence and gene expression
      profiling, and used in physiological studies. Stimulation of isolated acinar
      cells with carbachol (CCh), histamine or ATP was associated with marked decreases
      in cell volume (20 +/- 2% within 62 +/- 5 s) that were tightly correlated with
      increases in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) as revealed by
      simultaneous DIC and fluorescent indicator dye microscopy. Simultaneous imaging
      of cell volume and the Cl(-)-sensitive fluorophore SPQ indicated that the 20%
      shrinkage was associated with a fall of [Cl(-)](i) from 65 mm to 28 mm,
      reflecting loss of 67% of cell Cl(-) content, accompanied by parallel efflux of
      K(+). Upon agonist removal, [Ca(2+)](i) relaxed and the cells swelled back to
      resting volume via a bumetanide-sensitive Cl(-) influx pathway, likely to be
      NKCC1. Accordingly, agonist-induced serous acinar cell shrinkage and swelling are
      caused by activation of solute efflux and influx pathways, respectively, and cell
      volume reflects the secretory state of these cells. In contrast, elevation of
      cAMP failed to elicit detectible volume responses, or enhance those induced by
      submaximal [CCh], because the magnitude of the changes were likely to be below
      the threshold of detection using optical imaging. Finally, when stimulated with
      cholinergic or cAMP agonists, cells from mice that lacked CFTR, as well as wild
      type cells treated with a CFTR inhibitor, exhibited identical rates and
      magnitudes of shrinkage and Cl(-) efflux compared with control cells. These
      results provide insights into the molecular mechanisms of salt and water
      secretion by lung submucosal glands, and they suggest that while murine
      submucosal gland fluid secretion in response to cholinergic stimulation can
      originate from CFTR-expressing serous acinar cells, it is not dependent upon CFTR
      function.

PMID- 17525117
TI  - The association between patellar alignment and patellofemoral joint
      osteoarthritis features--an MRI study.
AB  - OBJECTIVE: The aim of our study was to evaluate the association between patellar
      alignment (using standard MRI images of extended knees) and MRI indices of
      patellofemoral (PF) osteoarthritis (OA) features. METHODS: In this cross
      sectional observational study, subjects were recruited to participate in the
      Boston Osteoarthritis of the Knee Study (BOKS). The association of patellar
      alignment [patellar length ratio (PLR), sulcus angle (SA), lateral patellar tilt
      angle (LPTA) and bisect offset (BO)] with measures of PF OA [cartilage morphology
      and bone marrow lesion (BML) in the medial and lateral PF compartment] were
      examined using a logistic regression model while adjusting for age, sex and BMI.
      RESULTS: Study sample comprised 126 males (mean age 68.0, BMI 31.2) and 87
      females (mean age 64.7, BMI 31.6). All measurements of patellar alignment were
      statistically significantly associated with cartilage morphology and BML in the
      lateral compartment of PF joint. PLR and SA were significantly associated with
      medial cartilage loss. With increasing PLR there was an increased prevalence of
      lateral and medial cartilage loss as well as of lateral BML. Increasing SA was
      positively associated with increased lateral and medial cartilage loss and
      lateral BML. LPTA range was negatively associated with lateral cartilage loss and
      BML. More laterally displaced patella (higher BO) was associated with increased
      lateral cartilage loss and BML. CONCLUSIONS: The results of our study clearly
      indicated that patellar alignment is associated with manifestations of PF OA such
      as cartilage thickness loss and BML.

PMID- 17525118
TI  - Pig conceptuses secrete estrogen and interferons to differentially regulate
      uterine STAT1 in a temporal and cell type-specific manner.
AB  - Conceptus trophectoderm and uterine luminal epithelial cells interact via
      endocrine, paracrine, and autocrine modulators to mediate pregnancy recognition
      and implantation. Pig conceptuses not only release estrogens for pregnancy
      recognition but also secrete interferons during implantation. Because interferon
      stimulated genes are increased by interferons secreted for pregnancy recognition
      in ruminants, we asked whether the interferon-stimulated gene, STAT1, is up
      regulated in pig endometrium by conceptus estrogens and/or interferons. STAT1
      expression in response to day of pregnancy, estrogen injection, and intrauterine
      infusion of conceptus secretory proteins in pigs indicated 1) estrogen increases
      STAT1 in luminal epithelial cells, 2) conceptus secretory proteins that contain
      interferons increase STAT1 in stroma, 3) STAT1 increases in close proximity to
      the conceptus, and 4) early estrogen results in conceptus death and no STAT1 in
      stroma. The interactions of estrogen and interferons to regulate cell-type
      specific expression of STAT1 highlight the complex interplay between endometrium
      and conceptus for pregnancy recognition and implantation.

PMID- 17525119
TI  - High basal levels of functional toll-like receptor 3 (TLR3) and noncanonical
      Wnt5a are expressed in papillary thyroid cancer and are coordinately decreased by
      phenylmethimazole together with cell proliferation and migration.
AB  - High basal levels of TLR3 and Wnt5a RNA are present in papillary thyroid
      carcinoma (PTC) cell lines consistent with their overexpression and
      colocalization in PTC cells in vivo. This is not the case in thyrocytes from
      normal tissue and in follicular carcinoma (FC) or anaplastic carcinoma (AC) cells
      or tissues. The basally expressed TLR3 are functional in PTC cells as evidenced
      by the ability of double-strand RNA (polyinosine-polycytidylic acid) to
      significantly increase the activity of transfected NF-kappaB and IFN-beta
      luciferase reporter genes and the levels of two end products of TLR3 signaling,
      IFN-beta and CXCL10. Phenylmethimazole (C10), a drug that decreases TLR3
      expression and signaling in FRTL-5 thyrocytes, decreases TLR3 levels and
      signaling in PTC cells in a concentration-dependent manner. C10 also decreased
      Wnt5a RNA levels coordinate with decreases in TLR3. E-cadherin RNA levels, whose
      suppression may be associated with high Wnt5a, increased with C10 treatment. C10
      simultaneously decreased PTC proliferation and cell migration but had no effect
      on the growth and migration of FC, AC, or FRTL-5 cells. C10 decreases high basal
      phosphorylation of Tyr705 and Ser727 on Stat3 in PTC cells and inhibits IL-6
      induced Stat3 phosphorylation. IL-6-induced Stat3 phosphorylation is important
      both in up-regulating Wnt5a levels and in cell growth. In sum, high Wnt5a levels
      in PTC cells may be related to high TLR3 levels and signaling; and the ability of
      phenylmethimazole (C10) to decrease growth and migration of PTC cells may be
      related to its suppressive effect on TLR3 and Wnt5a signaling, particularly Stat3
      activation.

PMID- 17525120
TI  - Are steroids obligatory mediators of luteinizing hormone/human chorionic
      gonadotropin-triggered resumption of meiosis in mammals?
AB  - Steroids mediate the gonadotropic stimulus of oocyte maturation in fish and
      amphibians. Such a role of steroids in mammals has not been confirmed until
      recently. A series of studies presented data suggesting that steroids might be
      involved in meiosis of mouse oocytes. Here we examined this suggestion using in
      vitro cultures of rat and mouse follicle-enclosed oocytes (FEOs) and cumulus
      enclosed oocytes (CEOs). In FEOs that mature only in response to gonadotropins or
      other stimuli, we tested the ability of steroids to trigger meiosis and whether
      addition of steroid receptor antagonists blocks LH/human chorionic gonadotropin
      stimulation of meiosis. In CEOs that mature spontaneously, we tested whether
      steroid antagonists block maturation and whether steroids overcome the inhibition
      of maturation by hypoxanthine (Hx), a mild inhibitor of meiotic resumption. The
      progesterone antagonists mifepristone (RU 486) and Organon 31710 as well as the
      estrogen antagonist faslodex did not prevent LH-triggered maturation of rat or
      mouse FEOs or the spontaneous maturation of CEOs. In accordance, the progesterone
      agonist promegestone (R5020) and estradiol did not stimulate the resumption of
      meiosis in rat and mouse FEOs, and both did not overcome the Hx inhibition of
      meiosis in rat and mouse CEOs. Flutamide, an androgen antagonist, did block
      meiosis in rat FEOs, but this action could not be affected by adding
      dihydrotestosterone, suggesting that it was not androgen receptor mediated.
      Flutamide did not affect spontaneous maturation of rat CEOs, and
      dihydrotestosterone could not stimulate meiosis inhibited by Hx. Thus, in
      contrast to lower vertebrates, in mammals, steroids do not seem to serve as an
      obligatory signal by which the somatic cells of the follicle transfer the
      gonadotropic stimulation of meiosis to the oocyte.

PMID- 17525121
TI  - Early pregnancy maternal endocrine insulin-like growth factor I programs the
      placenta for increased functional capacity throughout gestation.
AB  - In early pregnancy, the concentrations of IGFs increase in maternal blood.
      Treatment of pregnant guinea pigs with IGFs in early to midpregnancy enhances
      placental glucose transport and fetal growth and viability near term. In the
      current study, we determined whether exogenous IGFs altered placental gene
      expression, transport, and nutrient partitioning during treatment, which may then
      persist. Guinea pigs were infused with IGF-I, IGF-II (both 1 mg/kg x d) or
      vehicle sc from d 20-35 of pregnancy and killed on d 35 (term is 70 d) after
      administration of [(3)H]methyl-D-glucose (MG) and [(14)C]amino-isobutyric acid
      (AIB). IGF-I increased placental and fetal weights (+15 and +17%, respectively)
      and MG and AIB uptake by the placenta (+42 and +68%, respectively) and fetus (+59
      and +90%, respectively). IGF-I increased placental mRNA expression of the amino
      acid transporter gene Slc38a2 (+780%) and reduced that of Igf2 (-51%), without
      altering the glucose transporter Slc2a1 or Vegf and Igf1 genes. There were modest
      effects of IGF-I treatment on MG and AIB uptake by individual maternal tissues
      and no effect on plasma glucose, total amino acids, free fatty acids,
      triglycerides, and cholesterol concentrations. IGF-II treatment of the mother did
      not alter any maternal, fetal or placental parameter. In conclusion, exogenous
      IGF-I, but not IGF-II, in early pregnancy increases placental transport of MG and
      AIB, enhancing midgestational fetal nutrient uptake and growth. This suggests
      that early pregnancy rises in maternal circulating IGF-I play a major role in
      regulating placental growth and functional development and thus fetal growth
      throughout gestation.

PMID- 17525122
TI  - Cocaine- and amphetamine-regulated transcript (CART) is colocalized with the
      orexigenic neuropeptide Y and agouti-related protein and absent from the
      anorexigenic alpha-melanocyte-stimulating hormone neurons in the infundibular
      nucleus of the human hypothalamus.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is a recently discovered
      anorexigenic peptide. In rodents, CART inhibits food intake and is expressed in
      the anorexigenic alpha-MSH- but not in the orexigenic neuropeptide Y (NPY)- and
      agouti-related protein (AGRP)-synthesizing neurons of the arcuate nucleus. To
      understand whether CART is similarly expressed in feeding-related neuronal groups
      of the human hypothalamus as observed in rodents, colocalization of CART with
      alpha-MSH, NPY, AGRP, and melanin-concentrating hormone was studied using double
      labeling immunofluorescence and confocal microscopy on human hypothalamic tissues
      obtained at autopsy. Unlike in rodents, we observed that CART is absent from the
      perikarya and axons of alpha-MSH-synthesizing neurons, but expressed in
      approximately one third of NPY/AGRP neurons in the human infundibular nucleus. In
      the lateral hypothalamus of the humans, colocalization of CART and melanin
      concentrating hormone was observed, similar to that described in rodents. The
      anatomy of CART-containing neurons in the human infundibular nucleus differs
      markedly from that observed in the rodent brain, raising the question whether the
      colocalization of CART with orexigenic NPY and AGRP neurons is associated with an
      orexigenic role of CART in the human brain.

PMID- 17525123
TI  - Excess weight gain during the early postnatal period is associated with permanent
      reprogramming of brown adipose tissue adaptive thermogenesis.
AB  - Excess weight gain during the early postnatal period increases the risk of
      persistent obesity into adulthood and impacts on the subsequent risk for
      metabolic and cardiovascular diseases. The current study investigated the long
      term effect of early excess weight gain, through reduced nursing litter size, on
      body weight regulation and its relation to brown adipose tissue (BAT)
      thermogenesis. Animals raised in a small litter (SL, three pups per litter) were
      compared with those raised in a normal litter size (NL, eight pups per litter).
      BAT from young adult NL and SL rats, maintained under either ambient or cold
      conditions, were used for gene expression, morphological, and functional
      analysis. Compared with NL, SL rats showed excess weight gain, and adult SL
      animals had a reduced thermogenic capacity as displayed by lower levels of
      uncoupling protein 1 (UCP1). When exposed to cold, BAT from SL rats was less
      active and demonstrated reduced responsiveness to cold. Furthermore, reduction in
      transcript abundance of several lipid lipases and transcriptional regulators was
      observed in SL rats either at ambient temperature or under cold conditions.
      Finally, the expression of sympathetic beta 3-adrenergic receptor and the
      response to the sympathetic receptor agonist isoproterenol were decreased in SL
      rats. Overall, these observations provide the first evidence that postnatal
      excess weight gain results in abnormalities in BAT thermogenesis and sympathetic
      outflow, which likely increases susceptibility to obesity in adulthood.

PMID- 17525124
TI  - Beta-arrestin-dependent parathyroid hormone-stimulated extracellular signal
      regulated kinase activation and parathyroid hormone type 1 receptor
      internalization.
AB  - PTH regulates renal calcium homeostasis by actions on the distal nephron. PTH
      induced calcium transport in mouse distal convoluted tubule (DCT) cells requires
      activation of ERK1/2. ERK activation by beta-adrenergic receptors occurs in a
      biphasic manner and involves receptor internalization. An early rapid phase is
      beta-arrestin (betaAr) independent, whereas prolonged activation is betaAr
      dependent. We characterized PTH-stimulated ERK activation and the involvement of
      receptor internalization and betaAr dependence. In DCT cells, PTH transiently
      activated ERK maximally at 5 min and then returned to baseline. betaAr dependence
      of PTH receptor (PTH1R)-mediated ERK stimulation was assessed using mouse
      embryonic fibroblasts (MEFs) from betaAr1- and -2-null mice. In wild-type MEFs,
      PTH(1-34)-stimulated ERK activation peaked after 5 min, was 50% maximal after 15
      min, and then recovered to 80% of maximal stimulation by 30 min. In MEFs null for
      betaAr1 and -2, PTH-stimulated ERK activation peaked by 5 min and returned to
      baseline. The effect was identical in betaAr2-null MEFs. In betaAr1-null MEFs,
      ERK exhibited delayed activation and remained elevated. PTH-stimulated ERK
      activation and receptor endocytosis were not inhibited by the clathrin-binding
      domain of betaAr1 [Ar(319-418)]. Coexpression of the sodium proton exchanger
      regulatory factor 1 (NHERF1) with Ar(319-418) blocked PTH1R internalization. We
      conclude that PTH-stimulated ERK activation in DCT cells proceeds with a rapid
      but transient phase that may involve betaAr1. Furthermore, the betaAr-dependent
      late phase of ERK activation by PTH requires the participation of betaAr2 and
      PTH1R internalization.

PMID- 17525125
TI  - Regulation of central melanocortin signaling by interleukin-1 beta.
AB  - Anorexia and involuntary weight loss are common and debilitating complications of
      a number of chronic diseases and inflammatory states. Proinflammatory cytokines,
      including IL-1 beta, are hypothesized to mediate these responses through direct
      actions on the central nervous system. However, the neural circuits through which
      proinflammatory cytokines regulate food intake and energy balance remain to be
      characterized. Here we report that IL-1 beta activates the central melanocortin
      system, a key neuronal circuit in the regulation of energy homeostasis.
      Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus
      (ARC) were found to express the type I IL-1 receptor. Intracerebroventricular
      injection of IL-1 beta induced the expression of Fos protein in ARC POMC neurons
      but not in POMC neurons in the commissural nucleus of the tractus solitarius. We
      further show that IL-1 beta increases the frequency of action potentials of ARC
      POMC neurons and stimulates the release of alpha-MSH from hypothalamic explants
      in a dose-dependent fashion. Collectively, our data support a model in which IL-1
      beta increases central melanocortin signaling by activating a subpopulation of
      hypothalamic POMC neurons and stimulating their release of alpha-MSH.

PMID- 17525126
TI  - Somatostatin receptor subtype-2-deficient mice with diet-induced obesity have
      hyperglycemia, nonfasting hyperglucagonemia, and decreased hepatic glycogen
      deposition.
AB  - Hypersecretion of glucagon contributes to abnormally increased hepatic glucose
      output in type 2 diabetes. Somatostatin (SST) inhibits murine glucagon secretion
      from isolated pancreatic islets via somatostatin receptor subtype-2 (sst2). Here,
      we characterize the role of sst2 in controlling glucose homeostasis in mice with
      diet-induced obesity. Sst2-deficient (sst2(-/-)) and control mice were fed high
      fat diet for 14 wk, and the parameters of glucose homeostasis were monitored.
      Hepatic glycogen and lipid contents were quantified enzymatically and visualized
      histomorphologically. Enzymes regulating glycogen and lipid synthesis and
      breakdown were measured by real-time PCR and/or Western blot. Gluconeogenesis and
      glycogenolysis were determined from isolated primary hepatocytes and glucagon or
      insulin secretion from isolated pancreatic islets. Nonfasting glucose, glucagon,
      and fasting nonesterified fatty acids of sst2(-/-) mice were increased.
      Inhibition of glucagon secretion from sst2-deficient pancreatic islets by glucose
      or somatostatin was impaired. Insulin less potently reduced blood glucose
      concentration in sst2-deficient mice as compared with wild-type mice. Sst2
      deficient mice had decreased nonfasting hepatic glycogen and lipid content. The
      activity/expression of enzymes controlling hepatic glycogen synthesis of sst2(-/
      ) mice was decreased, whereas enzymes facilitating glycogenolysis and lipolysis
      were increased. Somatostatin and an sst2-selective agonist decreased glucagon
      induced glycogenolysis, without influencing de novo glucose production using
      cultured primary hepatocytes. This study demonstrates that ablation of sst2 leads
      to hyperglucagonemia. Increased glucagon concentration is associated with
      impaired glucose control in sst2(-/-) mice, resulting from decreased hepatic
      glucose storage, increased glycogen breakdown, and reduced lipid accumulation.
      Sst2 may constitute a therapeutic target to lower hyperglucagonemia in type 2
      diabetes.

PMID- 17525127
TI  - Adenoviral gene transfer in bovine adrenomedullary and murine pheochromocytoma
      cells: potential clinical and therapeutic relevance.
AB  - Recombinant adenoviruses (rAd) have been widely used as gene transfer vectors
      both in the laboratory and in human clinical trials. In the present study, we
      investigated the effects of adenoviral-mediated gene transfer in primary bovine
      adrenal chromaffin cells (BACC) and a murine pheochromocytoma cell line (MPC).
      Cells were infected with one of three nonreplicating E1/E3-deleted (E1(-)/E3(-))
      rAd vectors: Ad.GFP, expressing a green fluorescent protein (GFP); Ad.null,
      expressing no transgene; or Ad.C2.TK, expressing the herpes simplex virus-1
      thymidine kinase gene (TK). Forty-eight hours after exposure to Ad.GFP, the
      percentage of GFP-expressing BACC ranged from 23.5-97% in a dose-dependent manner
      and similarly from 1.06-84.4% in the MPC, indicating that adrenomedullary cells
      are a potentially valuable target for adenoviral-mediated gene transfer.
      Ultrastructural analysis, however, revealed profound changes in the nucleus and
      mitochondria of cells infected with rAd. Furthermore, infection of BACC with
      Ad.null was accompanied by a time- and dose-dependent decrease in cell survival
      due to the vector alone. Specific whole-cell norepinephrine uptake was also
      decreased in a time- and dose-dependent fashion in BACC. Infection of MPC cells
      with the Ad.C2.TK vector sensitized them to the cytotoxic effect of the antiviral
      drug ganciclovir, in direct proportion to the fraction of cells infected with the
      virus. We conclude that rAd may alter the structural and functional integrity of
      adrenomedullary cells, potentially interfering with the normal stress response.
      At the same time, in light of their ability to effectively deliver and express
      genes in pheochromocytoma cells, they may be applicable to the gene therapy of
      adrenomedullary tumors.

PMID- 17525128
TI  - Estrogen signaling via a linear pathway involving insulin-like growth factor I
      receptor, matrix metalloproteinases, and epidermal growth factor receptor to
      activate mitogen-activated protein kinase in MCF-7 breast cancer cells.
AB  - We present an integrated model of an extranuclear, estrogen receptor-alpha
      (ERalpha)-mediated, rapid MAPK activation pathway in breast cancer cells. In
      noncancer cells, IGF-I initiates a linear process involving activation of the IGF
      I receptor (IGF-IR) and matrix metalloproteinases (MMP), release of heparin
      binding epidermal growth factor (HB-EGF), and activation of EGF receptor (EGFR)
      dependent MAPK. 17beta-Estradiol (E2) rapidly activates IGF-IR in breast cancer
      cells. We hypothesize that E2 induces a similar linear pathway involving IGF-IR,
      MMP, HB-EGF, EGFR, and MAPK. Using MCF-7 breast cancer cells, we for the first
      time demonstrated that a sequential activation of IGF-IR, MMP, and EGFR existed
      in E2 and IGF-I actions, which was supported by evidence that the selective
      inhibitors of IGF-IR and MMP or knockdown of IGF-IR all inhibited E2- or IGF-I
      induced EGFR phosphorylation. Using the inhibitors and small inhibitory RNA
      strategies, we also demonstrated that the same sequential activation of the
      receptors occurred in E2-, IGF-I-, but not EGF-induced MAPK phosphorylation.
      Additionally, a HB-EGF neutralizing antibody significantly blocked E2-induced
      MAPK activation, further supporting our hypothesis. The biological effects of
      sequential activation of IGF-IR and EGFR on E2 stimulation of cell proliferation
      were also investigated. Knockdown or blockade of IGF-IR significantly inhibited
      E2- or IGF-I-stimulated but not EGF-induced cell growth. Knockdown or blockade of
      EGFR abrogated cell growth induced by E2, IGF-I, and EGF, indicating that EGFR is
      a downstream molecule of IGF-IR in E2 and IGF-I action. Together, our data
      support the novel view that E2 can activate a linear pathway involving the
      sequential activation of IGF-IR, MMP, HB-EGF, EGFR, and MAPK.

PMID- 17525129
TI  - Structure-function studies of allosteric agonism at M2 muscarinic acetylcholine
      receptors.
AB  - The M2 muscarinic acetylcholine receptor (mAChR) possesses at least one binding
      site for allosteric modulators that is dependent on the residues (172)EDGE(175),
      Tyr(177), and Thr(423). However, the contribution of these residues to actions of
      allosteric agonists, as opposed to modulators, is unknown. We created mutant M2
      mAChRs in which the charge of the (172)EDGE(175) sequence had been neutralized
      and each Tyr(177) and Thr(423) was substituted with alanine. Radioligand binding
      experiments revealed that these mutations had a profound inhibitory effect on the
      prototypical modulators gallamine, alcuronium, and heptane-1,7-bis-[dimethyl-3'
      phthalimidopropyl]-ammonium bromide (C7/3-phth) but minimal effects on the
      orthosteric antagonist [3H]N-methyl scopolamine. In contrast, the allosteric
      agonists 4-I-[3-chlorophenyl]carbamoyloxy)-2-butynyltrimethylammnonium chloride
      (McN-A-343), 4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl] piperidine hydrogen
      chloride (AC-42), and the novel AC-42 derivative 1-[3-(4-butyl-1
      piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone (77-LH-28-1) demonstrated an
      increased affinity or proportion of high-affinity sites at the combined EDGE-YT
      mutation, indicating a different mode of binding to the prototypical modulators.
      Subsequent functional assays of extracellular signal-regulated kinase (ERK)1/2
      phosphorylation and guanosine 5'-(gamma-[(35)S]thio)triphosphate
      ([(35)S]GTPgammaS) binding revealed minimal effects of the mutations on the
      orthosteric agonists acetylcholine (ACh) and pilocarpine but a significant
      increase in the efficacy of McN-A-343 and potency of 77-LH-28-1. Additional
      mutagenesis experiments found that these effects were predominantly mediated by
      Tyr(177) and Thr(423), rather than the (172)EDGE(175) sequence. The functional
      interaction between each of the allosteric agonists and ACh was characterized by
      high negative cooperativity but was consistent with an increased allosteric
      agonist affinity at the combined EDGE-YT mutant M2 mAChR. This study has thus
      revealed a differential role of critical allosteric site residues on the binding
      and function of allosteric agonists versus allosteric modulators of M2 mAChRs.

PMID- 17525130
TI  - Pulmonary aspergillosis: a clinical update.
AB  - Aspergillus spp may cause a variety of pulmonary diseases, depending on immune
      status and the presence of underlying lung disease. These manifestations range
      from invasive pulmonary aspergillosis in severely immunocompromised patients, to
      chronic necrotizing aspergillosis in patients with chronic lung disease and/or
      mildly compromised immune systems. Aspergilloma is mainly seen in patients with
      cavitary lung disease, while allergic bronchopulmonary aspergillosis is described
      in patients with hypersensitivity to Aspergillus antigens. Recent major advances
      in the diagnosis and management of pulmonary aspergillosis include the
      introduction of non-invasive tests, and the development of new antifungal agents,
      such as azoles and echinocandins, that significantly affect the management and
      outcome of patients with pulmonary aspergillosis. This review provides a clinical
      update on the epidemiology, risk factors, clinical presentation, diagnosis and
      management of the major syndromes associated with pulmonary aspergillosis.

PMID- 17525131
TI  - Differentiating between malignant and idiopathic pleural effusions: the value of
      diagnostic procedures.
AB  - BACKGROUND: Which diagnostic procedures should be used to differentiate between
      idiopathic and malignant pleural effusions, is not well established. AIM: To
      identify which parameters allow differentiation between idiopathic and malignant
      pleural effusions. DESIGN: Case-note review. METHODS: Over a 12-year period, we
      treated 1014 consecutive pleural effusion patients, of whom 346 were diagnosed as
      having an idiopathic or malignant aetiology. We analysed medical history, chest X
      ray, pleural fluid analysis (biochemical, microbiological and cytological), chest
      CT scan and additional examinations that were used according to clinical
      findings, and compared them with the eventual diagnosis and outcome. RESULTS:
      Eighty-three patients with idiopathic effusions and 263 with malignant effusions
      were included. Idiopathic pleural effusion resolved in 47 patients, improved in
      20 and persisted in 16. Biochemical pleural fluid analysis did not predict these
      outcomes. A history of neoplasm, chest X-ray and CT features, as well as
      additional examinations according to clinical findings, established a diagnosis
      or suspicion of malignancy in 256 (97.7%) of the 263 patients who received a
      diagnosis of malignant effusion. Diagnostic thoracoscopy was helpful in seven
      patients in whom malignant disease was strongly suspected, despite the absence of
      other pathological findings. DISCUSSION: Non-invasive complementary examinations
      generally allowed accurate differentiation between malignant and idiopathic
      effusions. Patients with idiopathic pleural effusions generally had favourable
      outcomes.

PMID- 17525132
TI  - Flight assessment in patients with respiratory disease: hypoxic challenge testing
      vs. predictive equations.
AB  - BACKGROUND: Predictive equations have been proposed as a simpler alternative to
      hypoxic challenge testing (HCT) for determining the risk of in-flight hypoxia.
      AIM: To assess agreement between hypoxic challenge testing (HCT) and predictive
      equations for assessment of in-flight hypoxia. DESIGN: Retrospective study.
      METHODS: Patients with chronic obstructive pulmonary disease (COPD) (n = 15),
      interstitial lung disease (ILD) (n = 15) and cystic fibrosis (CF) (n = 15) were
      studied. Spirometry was recorded prior to hypoxic inhalation and oxygen
      saturations (SpO2) were recorded before, after and during hypoxic inhalation.
      Blood gases were analysed before and after hypoxic inhalation and when SpO2 =
      85%. An HCT was performed using the Ventimask method. The PaO2 at altitude was
      estimated for each group using four published predictive equations, which use
      values of PaO2 (ground) and lung function measurements to predict altitude PaO2.
      Results were interpreted using the BTS recommendations for prescription of in
      flight oxygen post HCT. The Stuart Maxwell test of overall homogeneity was used
      to assess agreement between HCT results and each of the predictive equations.
      RESULTS: Ground PaO2 was significantly greater in patients with CF than either
      ILD or COPD (p < 0.05). PaO2 in all three groups significantly decreased
      following HCT. With the exception of equation 3, significantly fewer patients in
      each group would require in-flight O2 if prescription was based on HCT, compared
      to predictive equations (p < 0.05). DISCUSSION: Predictive equations considerably
      overestimate the need for in-flight O2, compared to HCT.

PMID- 17525133
TI  - Severe unexplained loin pain (loin pain haematuria syndrome): management and long
      term outcome.
AB  - BACKGROUND: The intractable and unexplained loin pain of severe 'loin pain
      haematuria syndrome' (LPHS) causes great psychosocial distress and disability.
      AIM: To examine the psychological factors in LPHS patients who had failed to
      respond to non-opiate analgesia, and explore the feasibility of conservative
      management. DESIGN: Retrospective review of case notes, medical and GP records,
      with follow up. METHODS: We studied 21 consecutive patients referred from
      specialist renal centres to a regional pain clinic. All records were reviewed,
      and patients received a comprehensive psychiatric and social assessment.
      Medication with pain-coping strategies was emphasized, and surgical solutions
      were discouraged. RESULTS: Patients' median age was 43 years (range 21-64) and
      duration of symptoms 11 (1-34) years. Sixteen were receiving opiates, and none
      had enduring benefit from surgery. Patients were divisible into three groups:
      twelve (57%) gave a history of recurrent, unexplained symptoms involving other
      parts of the body (somatoform disorder); seven had chronic loin pain;
      dissimulation was suspected in two. At follow-up (median 42 months), eight (38%)
      rated their pain absent or improved. Of the 11 whose pain was the same or worse,
      all were on opiates and seven had a somatoform disorder. A further two patients
      had developed 'other' medical problems. Despite our advice, three patients
      underwent major surgery for pain. DISCUSSION: We recommend that patients be
      managed in a regional pain clinic, where a multidisciplinary approach promotes
      self-management of pain. Patients who were able to accept conservative treatment,
      and taper or withdraw opiate analgesia, had a better prognosis.

PMID- 17525134
TI  - A comprehensive computational characterization of conserved mammalian intronic
      sequences reveals conserved motifs associated with constitutive and alternative
      splicing.
AB  - Orthologous mammalian introns contain many highly conserved sequences. Of these
      sequences, many are likely to represent protein binding sites that are under
      strong positive selection. In order to identify conserved protein binding sites
      that are important for splicing, we analyzed the composition of intronic
      sequences that are conserved between human and six eutherian mammals. We focused
      on all completely conserved sequences of seven or more nucleotides located in the
      regions adjacent to splice-junctions. We found that these conserved intronic
      sequences are enriched in specific motifs, and that many of these motifs are
      statistically associated with either alternative or constitutive splicing. In
      validation of our methods, we identified several motifs that are known to play
      important roles in alternative splicing. In addition, we identified several novel
      motifs containing GCT that are abundant and are associated with alternative
      splicing. Furthermore, we demonstrate that, for some of these motifs,
      conservation is a strong indicator of potential functionality since conserved
      instances are associated with alternative splicing while nonconserved instances
      are not. A surprising outcome of this analysis was the identification of a large
      number of AT-rich motifs that are strongly associated with constitutive splicing.
      Many of these appear to be novel and may represent conserved intronic splicing
      enhancers (ISEs). Together these data show that conservation provides important
      insights into the identification and possible roles of cis-acting intronic
      sequences important for alternative and constitutive splicing.

PMID- 17525135
TI  - Systematic analysis of genetic alterations in tumors using Cancer Genome
      WorkBench (CGWB).
AB  - Systematic investigations of genetic changes in tumors are expected to lead to
      greatly improved understanding of cancer etiology. To meet the analytical
      challenges presented by such studies, we developed the Cancer Genome WorkBench
      (http://cgwb.nci.nih.gov), the first computational platform to integrate clinical
      tumor mutation profiles with the reference human genome. A novel heuristic
      algorithm, IndelDetector, was developed to automatically identify
      insertion/deletion (indel) polymorphisms as well as indel somatic mutations with
      high sensitivity and accuracy. It was incorporated into an automated pipeline
      that detects genetic alterations and annotates their effects on protein coding
      and 3D structure. The ability of the system to facilitate identifying genetic
      alterations is illustrated in three projects with publicly accessible data.
      Mutagenesis in tumor DNA replication leading to complex genetic changes in the
      EGFR kinase domain is suggested by a novel deletion-insertion combination
      observed in paired tumor-normal lung cancer resequencing data. Automated analysis
      of 152 genes resequenced by the SeattleSNPs group was able to identify 91% of the
      1251 indel polymorphisms discovered by SeattleSNPs. In addition, our system
      discovered 518 novel indels in this data set, 451 of which were found to be valid
      by manual inspection of sequence traces. Our experience demonstrates that CGWB
      not only greatly improves the productivity and the accuracy of mutation
      identification, but also, through its data integration and visualization
      capabilities, facilitates identification of underlying genetic etiology.

PMID- 17525136
TI  - Identification of tau stem loop RNA stabilizers.
AB  - Alternative splicing of tau exon 10 produces tau isoforms with either 3 (3R) or 4
      (4R) repeated microtubule-binding domains. Increased ratios of 4R to 3R tau
      expression, above the physiological 1:1, leads to neurofibrillary tangles and
      causes neurodegenerative disease. An RNA stem loop structure plays a significant
      role in determining the ratio, with decreasing stability correlating with an
      increase in 4R tau mRNA expression. Recent studies have shown that
      aminoglycosides are able to bind and stabilize the tau stem loop in vitro,
      suggesting that other druglike small molecules could be identified and that such
      molecules might lead to decreased exon 10 splicing in vivo. The authors have
      developed a fluorescent high-throughput fluorescent binding assay and screened a
      library of approximately 110,000 compounds to identify candidate drugs that will
      bind the tau stem loop in vitro. In addition, they have developed a fluorescent
      based RNA probe to assay the stabilizing effects of candidate drugs on the tau
      stem loop RNA. These assays should be applicable to the general problem of
      identifying small molecules that interact with mRNA secondary structures.

PMID- 17525137
TI  - The pedunculopontine and peripeduncular nuclei: a tale of two structures.

PMID- 17525139
TI  - Distal myopathy caused by homozygous missense mutations in the nebulin gene.
AB  - We describe a novel, recessively inherited distal myopathy caused by homozygous
      missense mutations in the nebulin gene (NEB), in which other combinations of
      mutations are known to cause nemaline (rod) myopathy (NM). Two different missense
      mutations were identified in homozygous form in seven Finnish patients from four
      unrelated families with childhood or adult-onset foot drop. Both mutations, when
      combined in compound heterozygous form with more disruptive mutations in NEB, are
      known to cause NM. Hitherto, no patients with NM have been found to have two
      missense mutations in NEB. Muscle weakness predominantly affected ankle
      dorsiflexors, finger extensors and neck flexors, a distribution different both
      from the patterns of weakness seen in NM caused by NEB mutations, and those of
      the known recessively inherited distal myopathies. Singleton cases need to be
      distinguished from the Laing type of distal myopathy. Histologically, this
      myopathy differs from NM in that nemaline bodies were not detectable with routine
      light microscopy, and they were inconspicuous or absent even with electron
      microscopy. Rimmed vacuoles, commonly seen in other distal myopathies, were not a
      feature. We conclude that homozygous missense mutations in NEB cause a novel
      distal myopathy, predominantly involving lower leg extensor muscles, finger
      extensors and neck flexors.

PMID- 17525140
TI  - Pathological tau burden and distribution distinguishes progressive supranuclear
      palsy-parkinsonism from Richardson's syndrome.
AB  - Clinical syndromes associated with progressive supranuclear palsy-tau pathology
      now include progressive supranuclear palsy-parkinsonism (PSP-P), in addition to
      classic Richardson's syndrome (RS) and pure akinesia with gait freezing (PAGF).
      Although pathological heterogeneity of progressive supranuclear palsy (PSP) has
      also been established, attempts to correlate this with clinical findings have
      only rarely provided conclusive results. The aim of this study was to investigate
      whether regional variations in the types of tau lesions or differences in overall
      tau load may explain the clinical differences between the RS, PSP-P and PAGF.
      Quantitative tau pathology assessment was performed in 17 brain regions in 42
      cases of pathologically diagnosed PSP (22 RS, 14 PSP-P and 6 PAGF).
      Neurofibrillary tangles, tufted astrocytes, coiled bodies and thread pathology
      were quantitated and a grading system was developed separately for each region.
      Using these grades the overall tau load was calculated in each case. To establish
      a simplified system for grading the severity of tau pathology, all data were
      explored to identify the minimum number of regions that satisfactorily summarized
      the overall tau severity. The subthalamic nucleus, substantia nigra and globus
      pallidus were consistently the regions most severely affected by tau pathology.
      The mean severity in all regions of the RS group was higher than in PSP-P and
      PAGF, and the overall tau load was significantly higher in RS than in PSP-P (P =
      0.002). Using only the grade of coiled body + thread lesions in the substantia
      nigra, caudate and dentate nucleus, a reliable and repeatable 12-tiered grading
      system was established (PSP-tau score: 0, mild tau pathology, restricted
      distribution; >7, severe, widespread tau pathology). PSP-tau score was negatively
      correlated with disease duration (Spearman's rho -0.36, P = 0.028) and time from
      disease onset to first fall (Spearman's rho -0.49, P = 0.003). The PSP-tau score
      in PSP-P (median 3, range 0-5) was significantly lower than in RS (median 5,
      range 2-10, Mann-Whitney U, P < 0.001). The two cases carrying the tau-H2
      protective allele had the two lowest PSP-tau scores. We have identified
      significant pathological differences between the major clinical syndromes
      associated with PSP-tau pathology and the restricted, mild tau pathology in PSP-P
      supports its clinical distinction from RS. The grading system we have developed
      provides an easy-to-use and sensitive tool for the morphological assessment of
      PSP-tau pathology and allows for consideration of the clinical diversity that is
      known to occur in PSP.

PMID- 17525141
TI  - Moderate hyperglycaemia is associated with favourable outcome in acute lacunar
      stroke.
AB  - Hyperglycaemia in acute ischaemic stroke is traditionally associated with a
      worsened outcome. However, it is unclear whether the impact of hyperglycaemia on
      stroke outcome is similar in lacunar and non-lacunar infarctions. The relation
      between serum glucose measured within 6 h after stroke onset and functional
      outcome was investigated in 1375 ischaemic stroke patients who had been included
      in two placebo-controlled trials with lubeluzole. The endpoint was a favourable
      outcome, defined as a modified Rankin Scale score < or =2 at 3 months.
      Classification into lacunar (n = 168) and non-lacunar (n = 1207) strokes was
      based on clinical criteria according to the Oxfordshire Community Stroke Project
      and findings on brain CT scan. Hyperglycaemia was defined as blood glucose >8
      mmol/l. A possible concentration-dependent effect of glucose on outcome was
      investigated in both lacunar and non-lacunar stroke. Multivariate analysis showed
      that hyperglycaemia was associated with decreased odds of a favourable outcome in
      non-lacunar stroke (OR 0.60; 95% CI 0.41-0.88, P = 0.009), but with increased
      odds of a favourable outcome in lacunar stroke (multivariate OR for glucose >8
      mmol/l: 2.70; 95% CI 1.01-7.13, P = 0.048). In non-lacunar stroke, there appeared
      to be a concentration-effect relation, as the odds of favourable outcome
      gradually decreased with increasing glucose levels. In lacunar stroke, an
      association with favourable outcome was observed with glucose levels >8 mmol/l,
      but this beneficial effect diminished with more severe hyperglycaemia >12 mmol/l.
      In conclusion, hyperglycaemia has a detrimental effect in non-lacunar stroke, but
      moderate hyperglycaemia may be beneficial in lacunar stroke.

PMID- 17525142
TI  - Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage.
AB  - Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the
      pro-oxidant hemin/heme from blood, here we investigated the contribution of the
      inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH).
      We found that after induction of ICH, HO-1 proteins were highly detectable in the
      peri-ICH region predominantly in microglia/macrophages and endothelial cells.
      Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1-/
      ) mice than in wild-type controls 24 and 72 h after ICH. Although the brain water
      content did not appear to be significantly different, the protection in HO-1-/-
      mice was associated with a marked reduction in ICH-induced leucocyte
      infiltration, microglia/macrophage activation and free radical levels. These data
      reveal a previously unrecognized role of HO-1 in early brain injury after ICH.
      Thus, modulation of HO-1 signalling should be assessed further in clinical
      settings, especially for haemorrhagic states.

PMID- 17525143
TI  - The green-eyed monster and malicious joy: the neuroanatomical bases of envy and
      gloating (schadenfreude).
AB  - Facing a protagonist's emotional mental state can trigger social emotions (or
      'fortune of others' emotion), such as envy or gloating, which reflect one's
      assessment of the consequences of the other's fortune. Here we suggest that these
      social emotions are mediated by the mentalizing network. The present article
      explores the notion that the understanding of social competitive emotions is
      particularly impaired in patients with ventromedial (VM) prefrontal lesions. By
      manipulating a simple Theory of Mind (ToM) task, we tested the ability of
      patients with localized lesions to understand 'fortune of others' emotions: envy
      and gloating (schadenfreude). Patients were also assessed for their ability to
      recognize control physical and identification conditions. While envy is an
      example of a negative experience in the face of another's fortunes, gloat is
      thought to be a positive experience in the face of another's misfortune. Whereas
      in schadenfreude and envy the emotion of the self and the protagonist may be
      opposite, identification involves matching between the protagonist's and the
      observer's emotions. Patients with VM (N = 10) lesions (particularly in the right
      hemisphere), although showing intact performance on a basic first order ToM
      condition, and relatively preserved understanding of identification, did not
      recognize envy (F[6,76] = 3.491, P = 0.004) and gloating (F[6,76] = 3.738, P =
      0.003). Impaired recognition of gloating involved additionally lesions in the
      inferior parietal lobule (P = 0.001). Furthermore, while patients with lesions in
      the left hemisphere were more impaired in recognizing gloating (a positive
      emotion), right hemisphere patients were more impaired in recognizing envy (a
      negative emotion), suggesting that the valence of these emotions may also be
      affected by the asymmetry of the lesion (F[6,68] = 2.002, P = 0.011). In
      addition, the ability to identify these emotions was related to perspective
      taking abilities and ToM. We suggest that these results indicate that the
      mentalizing network including the VM has a fundamental role in mediating the
      understanding of competitive emotions such as envy and gloating.

PMID- 17525144
TI  - Is colour modulation an independent factor in human visual photosensitivity?
AB  - Considering that the role of colour in photosensitive epilepsy (PSE) remains
      unclear, we designed a study to determine the potential of different colours,
      colour combinations and white light to trigger photoparoxysmal responses (PPRs)
      under stringent controlled conditions. After assessing their photosensitivity to
      stroboscopic white light and black and white patterns, we studied 43 consecutive
      PSE patients (mean age 19 years, 34 women), using a specially designed colour
      stimulator. Stimuli included: pulse trains between 10 and 30 Hz of white light
      and of all primary colours, and also isoluminant alternating time-sequences of
      colours. Illuminance was kept constant at 100 lux. A progressive stepwise
      increase of the modulation-depth (MD) of the stimuli was used to determine PPRs
      threshold. Whereas all the 43 patients were found to be sensitive during the
      stroboscopic and pattern protocol, only 25 showed PPRs (Waltz's score >2) at
      least in one session when studied with the colour stimulator. Coloured stimuli
      elicited PPRs in all these patients, whereas white light did so only in 17
      patients. Of the primary colours, red elicited more PPRs (54 in 22 patients) and
      at a lower MD (max Z-score 0.93 at 10 Hz). Of the alternating sequences, the red
      blue was the most provocative stimulus, especially below 30 Hz (100% of patients,
      max Z-score: 1.65 at 15 Hz). Blue-green was the least provocative stimulus, since
      it elicited only seven PPRs in seven (28%) patients (max Z-score 0.44 at 10 Hz).
      Sensitivity to alternating colours was not correlated to sensitivity to
      individual colours. We conclude that colour sensitivity follows two different
      mechanisms: one, dependent on colour modulation, plays a role at lower
      frequencies (<30 Hz). Another, dependent on single-colour light intensity
      modulation correlates to white light sensitivity and is activated at higher
      frequencies. Our results suggest that the prescription of spectacles with
      coloured lenses, tailored to the patient, can be an effective preventative
      measure against visually induced seizures.

PMID- 17525145
TI  - Two 6-year-old twin girls with primary axillary bromhidrosis: discussion,
      differential diagnosis, and management options.

PMID- 17525146
TI  - Musical intervals in speech.
AB  - Throughout history and across cultures, humans have created music using pitch
      intervals that divide octaves into the 12 tones of the chromatic scale. Why these
      specific intervals in music are preferred, however, is not known. In the present
      study, we analyzed a database of individually spoken English vowel phones to
      examine the hypothesis that musical intervals arise from the relationships of the
      formants in speech spectra that determine the perceptions of distinct vowels.
      Expressed as ratios, the frequency relationships of the first two formants in
      vowel phones represent all 12 intervals of the chromatic scale. Were the formants
      to fall outside the ranges found in the human voice, their relationships would
      generate either a less complete or a more dilute representation of these specific
      intervals. These results imply that human preference for the intervals of the
      chromatic scale arises from experience with the way speech formants modulate
      laryngeal harmonics to create different phonemes.

PMID- 17525147
TI  - Structure of cholesterol helical ribbons and self-assembling biological springs.
AB  - We report the results of x-ray-scattering studies of individual helical ribbons
      formed in multicomponent solutions of cholesterol solubilized by various
      surfactants. The solutions were chemically defined lipid concentrate (CDLC) and
      model bile. In these and many analogous multicomponent surfactant-cholesterol
      solutions, helical ribbons of two well defined pitch angles, namely 11 degrees
      and 54 degrees, are formed. We have suggested previously that this remarkable
      stability results from an underlying crystalline structure of the sterol ribbon
      strips. Using a synchrotron x-ray source, we have indeed observed Bragg
      reflections from individual ribbons having 11 degrees pitch angle. We have been
      able to deduce the parameters of the unit cell. The crystal structure of these
      ribbons is similar to that of cholesterol monohydrate, with the important
      difference that the length of the unit cell perpendicular to the cholesterol
      layers is tripled. We discuss possible origins for this triplication as well as
      the connection between the crystalline structure and the geometrical form of the
      helical ribbons.

PMID- 17525148
TI  - Photoperiod reverses the effects of estrogens on male aggression via genomic and
      nongenomic pathways.
AB  - Despite recent discoveries of the specific contributions of genes to behavior,
      the molecular mechanisms mediating contributions of the environment are
      understudied. We demonstrate that the behavioral effects of estrogens on
      aggression are completely reversed by a discrete environmental signal, day
      length. Selective activation of either estrogen receptor alpha or beta decreases
      aggression in long days and increases aggression in short days. In the bed
      nucleus of the stria terminalis, one of several nuclei in a neural circuit that
      controls aggression, estrogen-dependent gene expression is increased in long days
      but not in short days, suggesting that estrogens decrease aggression by driving
      estrogen-dependent gene expression. Estradiol injections increased aggression
      within 15 min in short days but not in long days, suggesting that estrogens
      increase aggression in short days primarily via nongenomic pathways. These data
      demonstrate that the environment can dictate how hormones affect a complex
      behavior by altering the molecular pathways targeted by steroid receptors.

PMID- 17525149
TI  - Neuronal somatic ATP release triggers neuron-satellite glial cell communication
      in dorsal root ganglia.
AB  - It has been generally assumed that the cell body (soma) of a neuron, which
      contains the nucleus, is mainly responsible for synthesis of macromolecules and
      has a limited role in cell-to-cell communication. Using sniffer patch recordings,
      we show here that electrical stimulation of dorsal root ganglion (DRG) neurons
      elicits robust vesicular ATP release from their somata. The rate of release
      events increases with the frequency of nerve stimulation; external Ca(2+) entry
      is required for the release. FM1-43 photoconversion analysis further reveals that
      small clear vesicles participate in exocytosis. In addition, the released ATP
      activates P2X7 receptors in satellite cells that enwrap each DRG neuron and
      triggers the communication between neuronal somata and glial cells. Blocking L
      type Ca(2+) channels completely eliminates the neuron-glia communication. We
      further show that activation of P2X7 receptors can lead to the release of tumor
      necrosis factor-alpha (TNFalpha) from satellite cells. TNFalpha in turn
      potentiates the P2X3 receptor-mediated responses and increases the excitability
      of DRG neurons. This study provides strong evidence that somata of DRG neurons
      actively release transmitters and play a crucial role in bidirectional
      communication between neurons and surrounding satellite glial cells. These
      results also suggest that, contrary to the conventional view, neuronal somata
      have a significant role in cell-cell signaling.

PMID- 17525150
TI  - Mixture models and exploratory analysis in networks.
AB  - Networks are widely used in the biological, physical, and social sciences as a
      concise mathematical representation of the topology of systems of interacting
      components. Understanding the structure of these networks is one of the
      outstanding challenges in the study of complex systems. Here we describe a
      general technique for detecting structural features in large-scale network data
      that works by dividing the nodes of a network into classes such that the members
      of each class have similar patterns of connection to other nodes. Using the
      machinery of probabilistic mixture models and the expectation-maximization
      algorithm, we show that it is possible to detect, without prior knowledge of what
      we are looking for, a very broad range of types of structure in networks. We give
      a number of examples demonstrating how the method can be used to shed light on
      the properties of real-world networks, including social and information networks.

PMID- 17525151
TI  - Gastrointestinal dysfunction induced by early weaning is attenuated by delayed
      weaning and mast cell blockade in pigs.
AB  - Our previous work has demonstrated that weaning at 19 days of age has deleterious
      effects on mucosal barrier function in piglet intestine that are mediated through
      peripheral CRF receptor signaling pathways. The objectives of the present study
      were to assess the impact of piglet age on weaning-associated intestinal
      dysfunction and to determine the role that mast cells play in weaning-induced
      breakdown of mucosal barrier function. Nursing Yorkshire-cross piglets were
      either weaned at 19 days of age (early-weaned, n = 8) or 28 days of age (late
      weaned, n = 8) and housed in nursery pens. Twenty-four hours postweaning,
      segments of midjejunum and ascending colon from piglets within each weaning age
      group were harvested and mounted on Ussing chambers for measurements of
      transepithelial electrical resistance and serosal-to-mucosal [(3)H]mannitol
      fluxes. Early weaning resulted in reductions in transepithelial electrical
      resistance and increases in mucosal permeability to [(3)H]mannitol in the jejunum
      and colon (P < 0.01). In contrast, postweaning reductions in intestinal barrier
      function were not observed in piglets weaned at 28 days of age. Early-weaned
      piglet intestinal mucosa had increased expression of CRF receptor 1 protein,
      increased mucosal mast cell tryptase levels, and evidence of enhanced mast cell
      degranulation compared with late-weaned intestinal mucosa. Pretreatment of
      piglets with the mast cell stabilizer drug cromolyn, injected intraperitoneally
      30 min prior to weaning, abolished the early-weaning-induced intestinal barrier
      disturbances. Our results indicate that early-weaning stress induces mucosal
      dysfunction mediated by intestinal mast cell activation and can be prevented by
      delaying weaning.

PMID- 17525152
TI  - Detection of reactive oxygen species-sensitive thiol proteins by redox difference
      gel electrophoresis: implications for mitochondrial redox signaling.
AB  - Reactive oxygen species (ROS) produced by the mitochondrial respiratory chain can
      be a redox signal, but whether they affect mitochondrial function is unclear.
      Here we show that low levels of ROS from the respiratory chain under
      physiological conditions reversibly modify the thiol redox state of mitochondrial
      proteins involved in fatty acid and carbohydrate metabolism. As these thiol
      modifications were specific and occurred without bulk thiol changes, we first had
      to develop a sensitive technique to identify the small number of proteins
      modified by endogenous ROS. In this technique, redox difference gel
      electrophoresis, control, and redox-challenged samples are labeled with different
      thiol-reactive fluorescent tags and then separated on the same two-dimensional
      gel, enabling the sensitive detection of thiol redox modifications by changes in
      the relative fluorescence of the two tags within a single protein spot, followed
      by protein identification by mass spectrometry. Thiol redox modification affected
      enzyme activity, suggesting that the reversible modification of enzyme activity
      by ROS from the respiratory chain may be an important and unexplored mode of
      mitochondrial redox signaling.

PMID- 17525153
TI  - Evidence against functional interaction between aquaporin-4 water channels and
      Kir4.1 potassium channels in retinal Muller cells.
AB  - Indirect evidence suggests that the Muller/glial cell water channel aquaporin-4
      (AQP4) modulates K(+) channel function of the closely associated Kir4.1 protein.
      We used patch clamp to compare Kir4.1 K(+) channel function in freshly isolated
      Muller cells from retinas of wild-type (+/+) and AQP4 knock-out (-/-) mice.
      Immunocytochemistry showed a comparable Kir4.1 protein expression pattern in
      Muller cells from +/+ and -/- retinas, with greatest expression at their end
      feet. Osmotic water permeability was >4-fold reduced in -/- than in +/+ Muller
      cells. Resting membrane potential did not differ significantly in +/+ versus -/-
      Muller cells (-64 +/- 1 versus -64 +/- 1 mV, S.E., n = 24). Whole-cell K(+)
      currents recorded with a micropipette inserted into the cell soma were Ba(2+)
      sensitive and showed no significant differences in magnitude in +/+ versus -/-
      Muller cells (1.3 +/- 0.1 versus 1.2 +/- 0.1 nA at -160 mV) or in inwardly
      rectifying current-voltage relationships. Spatially resolved K(+) currents
      generated by pulsed K(+) injections along Muller cell bodies were also comparable
      in +/+ versus -/- Muller cells. Single-channel cell-attached patch clamp showed
      comparable unitary conductance, current-voltage data, and open probability in +/+
      versus -/- Muller cells. Thus, contrary to the generally accepted view, our
      results provide direct evidence against functionally significant AQP4 modulation
      of Muller cell Kir4.1 K(+) channel function.

PMID- 17525154
TI  - Characterization of cis-autoproteolysis of polycystin-1, the product of human
      polycystic kidney disease 1 gene.
AB  - Polycystin-1 (PC1), the PKD1 gene product, plays a critical role in renal tubule
      diameter control and disruption of its function causes cyst formation in human
      autosomal dominant polycystic kidney disease. Recent evidence shows that PC1
      undergoes cleavage at the juxtamembrane G protein-coupled receptor proteolytic
      site (GPS), a process likely to be essential for its biological activity. Here we
      further characterized the proteolytic cleavage of PC1 at the GPS domain. We
      determined the actual cleavage site to be between leucine and threonine of the
      tripeptide HLT(3049) of human PC1. Cleavage occurs in the early intracellular
      secretory pathway and requires initial N-glycan attachment but not its subsequent
      trimming. We provide evidence that the cleavage occurs via a cis-autoproteolytic
      mechanism involving an ester intermediate as shown for Ntn hydrolases and EMR2.

PMID- 17525155
TI  - Diminished GATA4 protein levels contribute to hyperglycemia-induced cardiomyocyte
      injury.
AB  - Hyperglycemia is an independent risk factor for diabetic heart failure. However,
      the mechanisms that mediate hyperglycemia-induced cardiac damage remain poorly
      understood. The transcription factor GATA4 is essential for cardiac homeostasis,
      and its protein levels are dramatically reduced in the heart in response to
      diverse pathologic stresses. In this study, we investigated if hyperglycemia
      affects GATA4 expression in cardiomyocytes and if enhancing GATA4 signaling could
      attenuate hyperglycemia-induced cardiomyocyte injury. In cultured rat
      cardiomyocytes, high glucose (HG, 25 or 40 mm) markedly reduced GATA4 protein
      levels as compared with normal glucose (NG, 5.5 mm). Equal amount of mannitol did
      not affect GATA4 protein expression (NG, 100 +/- 12%; mannitol, 97 +/- 8%, versus
      HG, 43 +/- 16%, p < 0.05). The GATA4 mRNA content, either steady-state or
      polysome-associated, remained unchanged. HG-induced GATA4 reduction was reversed
      by MG262, a specific proteasome inhibitor. HG did not activate the ubiquitin
      proteasome system (UPS) in cardiomyocytes as indicated by a UPS reporter, nor did
      it increase the peptidase activities or protein expression of the proteasomal
      subunits. However, the mRNA levels of ubiquitin-protein isopeptide ligase (E3)
      carboxyl terminus of Hsp70-interacting protein (CHIP) were markedly increased in
      HG-treated cardiomyocytes. CHIP overexpression promoted GATA4 protein
      degradation, whereas small interfering RNA-mediated CHIP knockdown prevented HG
      induced GATA4 depletion. Moreover, overexpression of GATA4 blocked HG-induced
      cardiomyocyte death. Also, GATA4 protein levels were diminished in the hearts of
      streptozotocin and db/db diabetic mice (44 +/- 7% and 67 +/- 13% of control, p <
      0.05), which correlated with increased CHIP mRNA abundance. In summary, increased
      GATA4 protein degradation may be an important mechanism that contributes to
      hyperglycemic cardiotoxicity.

PMID- 17525156
TI  - Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in
      transcribed regions to promote elongation.
AB  - Histone methylation is a reversible modification regulated by the antagonistic
      functions of residue-specific histone methyltransferases and demethylases.
      Although methylation of histone H3 at lysines 4 and 36 is linked to
      transcription, the roles of histone demethylases in transcription regulation are
      not understood. Here we show that overexpression of either Jhd1 or Rph1, two JmjC
      domain proteins, bypasses the requirement for the positive elongation factor gene
      BUR1. Biochemical analysis and chromatin immunoprecipitation experiments indicate
      that Rph1 functions as a specific demethylase for H3 K36me3 and K36me2, directly
      regulating Lys(36) methylation in transcribed regions. Both Jhd1 and Rph1 are
      required for normal levels of RNA polymerase II cross-linking to genes. Taken
      together, these findings indicate that a general function of histone demethylases
      for H3 Lys(36) is to promote transcription elongation by antagonizing repressive
      Lys(36) methylation by Set2.

PMID- 17525157
TI  - Empty class II major histocompatibility complex created by peptide photolysis
      establishes the role of DM in peptide association.
AB  - DM catalyzes the exchange of peptides bound to Class II major histocompatibility
      complex (MHC) molecules. Because the dissociation and association components of
      the overall reaction are difficult to separate, a detailed mechanism of DM
      catalysis has long resisted elucidation. UV irradiation of DR molecules loaded
      with a photocleavable peptide (caged Class II MHC molecules) enabled synchronous
      and verifiable evacuation of the peptide-binding groove and tracking of early
      binding events in real time by fluorescence polarization. Empty DR molecules
      generated by photocleavage rapidly bound peptide but quickly resolved into
      species with substantially slower binding kinetics. DM formed a complex with
      empty DR molecules that bound peptide with even faster kinetics than empty DR
      molecules just having lost their peptide cargo. Mathematical models demonstrate
      that the peptide association rate of DR molecules is substantially higher in the
      presence of DM. We therefore unequivocally establish that DM contributes directly
      to peptide association through formation of a peptide-loading complex between DM
      and empty Class II MHC. This complex rapidly acquires a peptide analogous to the
      MHC class I peptide-loading complex.

PMID- 17525158
TI  - Laeverin/aminopeptidase Q, a novel bestatin-sensitive leucine aminopeptidase
      belonging to the M1 family of aminopeptidases.
AB  - Laeverin/aminopeptidase Q (APQ) is a cell surface protein specifically expressed
      on human embryo-derived extravillous trophoblasts that invades the uterus during
      placentation. The cDNA cloning of Laeverin/APQ revealed that the sequence encodes
      a protein with 990 amino acid residues, and Laeverin/APQ contains the HEXXHX(18)E
      gluzincin motif, which is characteristic of the M1 family of aminopeptidases,
      although the exopeptidase motif of the family, GAMEN, is uniquely substituted for
      the HAMEN sequence. In this study, we expressed a recombinant human Laeverin/APQ
      using a baculovirus expression system, purified to homogeneity, and characterized
      its enzymatic properties. It was found that Laeverin/APQ had a broad substrate
      specificity toward synthetic substrate, although it showed a preference for Leu-4
      methylcoumaryl-7-amide. Searching natural substrates, we found that Laeverin/APQ
      was able to cleave the N-terminal amino acid of several peptides such as
      angiotensin III, kisspeptin-10, and endokinin C, which are abundantly expressed
      in the placenta. In contrast to the case with other M1 aminopeptidases, bestatin
      inhibited the aminopeptidase activity of Laeverin/APQ much more effectively than
      other known aminopeptidase inhibitors. These results indicate that Laeverin/APQ
      is a novel bestatin-sensitive leucine aminopeptidase and suggest that the enzyme
      plays important roles in human placentation by regulating biological activity of
      key peptides at the embryo-maternal interface.

PMID- 17525159
TI  - Regulation of the gene encoding GPR40, a fatty acid receptor expressed
      selectively in pancreatic beta cells.
AB  - GPR40 is a G protein-coupled receptor expressed preferentially in pancreatic beta
      cells. It is activated by long-chain fatty acids and has been implicated in
      mediating physiological and pathological effects of long-chain fatty acids on
      beta cells. We mapped the GPR40 transcription start site to a location 1044 bp
      upstream of the translation start site. This permitted definition of the GPR40
      core promoter and the organization of the gene, which comprises a 24-bp non
      coding exon, a 698-bp intron and a 4402-bp second exon, containing the entire
      protein coding sequence. Sequence analysis of the GPR40 locus revealed three
      evolutionarily conserved regions upstream to the translation start site (HR1
      HR3). DNase I-hypersensitive sites were present in the HR2 and HR3 regions in
      beta cells but not in non-beta cells. The 5'-flanking region of the GPR40 gene
      was capable of directing transcriptional activity selectively in beta cells. An
      important component of this is attributable to the HR2 region, which showed
      strong beta cell-specific enhancer activity. Systematic mutagenesis of HR2
      revealed several important sub-regions. Mutagenesis of sub-regions 4-5, and 9
      reduced transcriptional activity by approximately 60 and 40%, respectively. These
      sub-regions can bind the beta cell-specific transcription factors PDX1 and BETA2,
      respectively, both in vitro and in vivo. Thus, cell-specific expression of the
      GPR40 gene involves a characteristic chromatin organization of the locus and is
      controlled at the transcriptional level through HR2, a potent beta cell-specific
      enhancer.

PMID- 17525160
TI  - O-linked glycosylation at threonine 27 protects the copper transporter hCTR1 from
      proteolytic cleavage in mammalian cells.
AB  - The major human copper uptake protein, hCTR1, has 190 amino acids and a predicted
      mass of 21 kDa. hCTR1 antibodies recognize multiple bands in SDS-PAGE centered at
      35 kDa. Part of this increased mass is due to N-linked glycosylation at Asn-15.
      We show that in mammalian cells the N15Q mutant protein trafficked to the plasma
      membrane and mediated copper uptake at 75% of the rate of wild-type hCTR1. We
      demonstrate that the extracellular amino terminus of hCTR1 also contains O-linked
      polysaccharides. Glycosidase treatment that removed O-linked sugars reduced the
      apparent mass of hCTR1 or N15Q mutant protein by 1-2 kDa. Expression of amino
      terminal truncations and alanine substitution mutants of hCTR1 in HEK293 and MDCK
      cells localized the site of O-linked glycosylation to Thr-27. Expression of
      alanine substitutions at Thr-27 resulted in proteolytic cleavage of hCTR1 on the
      carboxyl side of the T27A mutations. This cleavage produced a 17-kDa polypeptide
      missing approximately the first 30 amino acids of hCTR1. Expression of wild-type
      hCTR1 in mutant Chinese hamster ovary cells that were unable to initiate O
      glycosylation also resulted in hCTR1 cleavage to produce the 17-kDa polypeptide.
      The 17-kDa hCTR1 polypeptide was located in the plasma membrane and mediated
      copper uptake at about 50% that of the rate of wild-type hCTR1. Thus, O-linked
      glycosylation at Thr-27 is necessary to prevent proteolytic cleavage that removes
      half of the extracellular amino terminus of hCTR1 and significantly impairs
      transport activity of the remaining polypeptide.

PMID- 17525161
TI  - Protein kinase Czeta abrogates the proapoptotic function of Bax through
      phosphorylation.
AB  - Protein kinase Czeta (PKCzeta) is an atypical PKC isoform that plays an important
      role in supporting cell survival but the mechanism(s) involved is not fully
      understood. Bax is a major member of the Bcl-2 family that is required for
      apoptotic cell death. Because Bax is extensively co-expressed with PKCzeta in
      both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cells,
      it is possible that Bax may act as the downstream target of PKCzeta in regulating
      survival and chemosensitivity of lung cancer cells. Here we discovered that
      treatment of cells with nicotine not only enhances PKCzeta activity but also
      results in Bax phosphorylation and prolonged cell survival, which is suppressed
      by a PKCzeta specific inhibitor (a myristoylated PKCzeta pseudosubstrate
      peptide). Purified, active PKCzeta directly phosphorylates Bax in vitro.
      Overexpression of wild type or the constitutively active A119D but not the
      dominant negative K281W PKCzeta mutant results in Bax phosphorylation at serine
      184. PKCzeta co-localizes and interacts with Bax at the BH3 domain. Specific
      depletion of PKCzeta by RNA interference blocks nicotine-stimulated Bax
      phosphorylation and enhances apoptotic cell death. Intriguingly, forced
      expression of wild type or A119D but not K281W PKCzeta mutant results in
      accumulation of Bax in cytoplasm and prevents Bax from undergoing a
      conformational change with prolonged cell survival. Purified PKCzeta can directly
      dissociate Bax from isolated mitochondria of C2-ceramide-treated cells. Thus,
      PKCzeta may function as a physiological Bax kinase to directly phosphorylate and
      interact with Bax, which leads to sequestration of Bax in cytoplasm and
      abrogation of the proapoptotic function of Bax.

PMID- 17525162
TI  - Intranuclear protein transduction through a nucleoside salvage pathway.
AB  - Regulation of gene expression by intranuclear transduction of macromolecules such
      as transcription factors is an alternative to gene therapy for the treatment of
      numerous diseases. The identification of an effective intranuclear delivery
      vehicle and pathway for the transport of therapeutic macromolecules across plasma
      and nuclear membranes, however, has posed a significant challenge. The anti-DNA
      antibody fragment 3E10 Fv has received attention as a novel molecular delivery
      vehicle due to its penetration into living cells with specific nuclear
      localization, absence of toxicity, and successful delivery of therapeutic cargo
      proteins in vitro and in vivo. Elucidation of the pathway that allows 3E10 Fv to
      cross cell membranes is critical to the development of new molecular therapies.
      Here we show that 3E10 Fv penetrates cells through a nucleoside salvage
      transporter. 3E10 Fv is unable to penetrate into cells deficient in the
      equilibrative nucleoside transporter ENT2, and reconstitution of ENT2 into ENT2
      deficient cells restores 3E10 Fv transport into cell nuclei. Our results
      represent the first demonstration of protein transport through a nucleoside
      salvage pathway. We expect that our finding will facilitate a variety of methods
      of gene regulation in the treatment of human diseases, open up new avenues of
      research in nucleoside salvage pathways, and enhance our understanding of the
      pathophysiology of autoimmune diseases.

PMID- 17525163
TI  - Sumoylation of Oct4 enhances its stability, DNA binding, and transactivation.
AB  - Transcription factor Oct4 is a master regulator affecting the fate of pluripotent
      stem cells and germ cell precursors. Oct4 expression is tightly regulated, and
      small changes in expression level can have dramatic effects on differentiation or
      oncogenesis. Post-translational modifications including phosphorylation and
      ubiquitination have been reported to regulate Oct4 transcriptional activity. Here
      we show that Oct4 is a target for small ubiquitin-related modifier (SUMO)-1
      modification in vivo and in vitro. Sumoylation of Oct4 occurs at a single lysine,
      Lys(118), located at the end of the amino-terminal transactivation domain and
      next to the Pit1-Oct-Unc86 (POU) DNA binding domain. SUMO-1 and Oct4 colocalize
      at several promoter sequences in vivo, and a fraction of Oct4 molecules
      colocalized with SUMO-1 in nuclear aggregates. Sumoylation of Oct4 led to
      significantly increased Oct4 stability and increased DNA binding. In addition,
      SUMO-1 cotransfection led to augmented Oct4 transactivation potential that was
      reduced when the Oct4 sumoylation target site was mutated. Therefore, sumoylation
      of Oct4 results in increased stability, DNA binding, and transactivation and
      provides an important mechanism to regulate Oct4 activity.

PMID- 17525164
TI  - Activation of 5'-AMP-activated kinase with diabetes drug metformin induces casein
      kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2.
AB  - Metformin is one of the most commonly used first line drugs for type II diabetes.
      Metformin lowers serum glucose levels by activating 5'-AMP-activated kinase
      (AMPK), which maintains energy homeostasis by directly sensing the AMP/ATP ratio.
      AMPK plays a central role in food intake and energy metabolism through its
      activities in central nervous system and peripheral tissues. Since food intake
      and energy metabolism is synchronized to the light-dark (LD) cycle of the
      environment, we investigated the possibility that AMPK may affect circadian
      rhythm. We discovered that the circadian period of Rat-1 fibroblasts treated with
      metformin was shortened by 1 h. One of the regulators of the period length is
      casein kinase Iepsilon (CKIepsilon), which by phosphorylating and inducing the
      degradation of the circadian clock component, mPer2, shortens the period length.
      AMPK phosphorylates Ser-389 of CKIepsilon, resulting in increased CKIepsilon
      activity and degradation of mPer2. In peripheral tissues, injection of metformin
      leads to mPer2 degradation and a phase advance in the circadian expression
      pattern of clock genes in wild-type mice but not in AMPK alpha2 knock-out mice.
      We conclude that metformin and AMPK have a previously unrecognized role in
      regulating the circadian rhythm.

PMID- 17525165
TI  - Mechanical stretching stimulates smooth muscle cell growth, nuclear protein
      import, and nuclear pore expression through mitogen-activated protein kinase
      activation.
AB  - Although it is known that mechanical stretching of cells can induce significant
      increases in cell growth and shape, the intracellular signaling pathways that
      induce this response at the level of the cell nucleus is unknown. The transport
      of molecules from the cell cytoplasm to the nucleoplasm through the nuclear pore
      is a key pathway through which gene expression can be controlled in some
      conditions. It is presently unknown if mechanical stimuli can induce changes in
      nuclear pore expression and/or function. The purpose of the present investigation
      was to determine if mechanical stretching of a cell will alter nuclear protein
      import and the mechanisms that may be responsible. Vascular smooth muscle cells
      that were mechanically stretched exhibited an increase in proliferating cell
      nuclear antigen expression, cell number, and cell size within 24-48 h. Cells were
      microinjected with marker proteins for nuclear import. Nuclear protein import was
      significantly stimulated in stretched cells when compared with control. This was
      associated with an increase in the expression of nuclear pore proteins as
      detected by Western blots. Inhibition of the MAPK pathway blocked the stretch
      induced stimulation of both cell proliferation and nuclear protein import. We
      conclude that nuclear protein import and nuclear pore density can adapt to
      mechanical stimuli during the process of cell growth through a MAPK-mediated
      mechanism.

PMID- 17525166
TI  - Utility and sensitivity of the sore throat pain model: results of a randomized
      controlled trial on the COX-2 selective inhibitor valdecoxib.
AB  - The sore throat pain model was employed in this randomized, placebo-controlled
      trial to examine the sensitivity of the model in testing the efficacy of
      valdecoxib as an acute analgesic drug. Changes were made to the study design by
      employing a different diagnostic index for tonsillo-pharyngitis, a different
      rating scale (derived from Lasagna's pain thermometer), and alternative analyses,
      individual responder rates. Under double-blind conditions, 197 patients with
      painful pharyngitis were randomly allocated to valdecoxib 20 mg bid (n = 65),
      valdecoxib 40 mg qd (n = 66), or placebo (n = 66) for 24 hours. The expanded
      Tonsillo-Pharyngitis Assessment and the Lasagna Pain Scale were validated as
      sensitive study instruments. Both dosage regimens provided significantly greater
      pain relief compared with placebo on standard efficacy measures over the 24-hour
      study (all P < .05). Tests for individual response (eg, percentage of patients
      with at least moderate relief) confirmed these results, and other response rates
      identified the high sensitivity of the model itself (eg, only 5% of placebo
      treated patients achieved >or=50% of maximum total pain relief over 6 hours).
      These findings indicate that sore throat is a sensitive model to assess analgesic
      efficacy.

PMID- 17525167
TI  - Argatroban anticoagulation in obese versus nonobese patients: implications for
      treating heparin-induced thrombocytopenia.

PMID- 17525168
TI  - Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy
      subjects.
AB  - Fosaprepitant is an intravenous formulation of aprepitant, an oral NK1 antagonist
      used to prevent chemotherapy-induced nausea and vomiting. This randomized study
      was designed to evaluate fosaprepitant in polysorbate 80 vehicle for tolerability
      and bioequivalency to aprepitant. Tolerability was assessed by physical and
      laboratory examinations and adverse events. Plasma collected for 72 hours was
      assayed for aprepitant and fosaprepitant. Analysis of variance models were
      applied to natural log-transformed aprepitant area under the curve (AUC) data.
      Fosaprepitant up to 150 mg (1 mg/mL) was generally well tolerated. Fosaprepitant
      115 mg was AUC bioequivalent to aprepitant 125 mg; the 90% confidence interval
      for the geometric mean ratio of aprepitant AUC for fosaprepitant 115
      mg/aprepitant 125 mg fell within prespecified equivalence bounds of 0.80 to 1.25.

PMID- 17525169
TI  - Pharmacological risk factors for amphotericin B nephrotoxicity in children.

PMID- 17525171
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 17525170
TI  - The C-terminal domain of RNA Pol II helps ensure that editing precedes splicing
      of the GluR-B transcript.
AB  - The C-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II)
      influences many steps in the synthesis of an mRNA and helps control the final
      destiny of the mature transcript. ADAR2 edits RNA by converting adenosine to
      inosine within double-stranded or structured RNA. Site-selective A-to-I editing
      often occurs at sites near exon/intron borders, where it depends on intronic
      sequences for substrate recognition. It is therefore essential that editing
      precedes splicing. We have investigated whether there is coordination between
      ADAR2 editing and splicing of the GluR-B pre-mRNA. We show that the CTD is
      required for efficient editing at the R/G site one base upstream of a 5'-splice
      site. The results suggest that the CTD enhances editing at the R/G site by
      preventing premature splicing that would remove the intronic recognition sites
      for ADAR2. Editing at the GluR-B Q/R site, 24 bases upstream of the intron 11 5'
      splice site, stimulates splicing at this intron. Furthermore, unlike previously
      studied introns, the CTD actually inhibits excision of intron 11, which includes
      the complementary recognition sequences for the Q/R editing site. In summary,
      these results show that the CTD and ADAR2 function together to enforce the order
      of events that allows editing to precede splicing, and they furthermore suggest a
      new role for the CTD as a coordinator of two interdependent pre-mRNA processing
      events.

PMID- 17525172
TI  - Heritable features of the optic disc: a novel twin method for determining genetic
      significance.
AB  - PURPOSE: Numerous genetic diseases and environmental stimuli affect optic nerve
      morphology. The purpose of this study was to identify the principal heritable
      components of visible optic nerve head structures in a population-based sample of
      twins. METHODS: Fifteen optic nerve specialists viewed stereoscopic optic nerve
      head photographs (Stereo Viewer-II; Pentax Corp., Tokyo, Japan) from 50 randomly
      selected monozygotic or dizygotic twin pairs. Before viewing, each expert was
      questioned about which optic nerve head traits they believed were inherited.
      After viewing a standardized teaching set, the experts indicated which twin pairs
      they thought were monozygotic. Participants were then questioned about how their
      decisions were reached. A rank-ordered Rasch analysis was used to determine the
      relative weighting and value applied to specific optic nerve head traits.
      RESULTS: The proportion of twin pairs for which zygosity was correctly identified
      ranged from 74% to 90% (median, 82%) across the panel. Experts who correctly
      identified the zygosity in more than 85% of cases placed most weighting on shape
      and size of the optic disc and cup, whereas experts with the lowest scores placed
      greater weighting on the optic nerve head vasculature in reaching their
      decisions. CONCLUSIONS: In determining the genetic components of the optic nerve
      head, the results of this study suggest that the shape and size of the optic disc
      and cup are more heritable and should receive a greater priority for
      quantification than should vascular features.

PMID- 17525173
TI  - Retinoblastoma tumor vessel maturation impacts efficacy of vessel targeting in
      the LH(BETA)T(AG) mouse model.
AB  - PURPOSE: The aim of this study was to quantify tumor cell proliferation and
      growth, analyze tumor blood vessel development, and determine the efficacy of
      antiangiogenic and angiostatic therapy in targeting mature vessels in retinal
      tumors of the LH(BETA)T(AG) mouse model for retinoblastoma. METHODS:
      LH(BETA)T(AG) mouse retinas were analyzed at 4, 8, 12, and 16 weeks of age. Tumor
      burden was analyzed by histology; cell proliferation, vessel density,
      angiogenesis, and vessel maturation were detected by immunofluorescence. To
      assess the efficacy of mature vessel targeting, 16-week-old mice were treated
      with single subconjunctival injections of the selective vascular-targeting drug
      combretastatin A4 prodrug (CA4P) or anecortave acetate, and eyes were analyzed 1
      day and 1 week after injection to determine microvessel density and the number of
      angiogenic and mature vessels. RESULTS: Increased cell proliferation and
      angiogenesis were detected in the retinal inner nuclear layer (INL) before
      morphologic neoplastic changes were evident. As tumor size increased,
      angiogenesis diminished concomitantly with the appearance of mature vessels.
      Treatment with CA4P and anecortave acetate resulted in significant reductions in
      total vessel density. However, neither drug reduced the amount of alpha-smooth
      muscle actin (SMA)-positive, mature vessels. CONCLUSIONS: Results of this study
      provide new insight into the relationship between tumor growth and blood vessel
      development in the LH(BETA)T(AG) mouse and establish the framework for defining
      the selective action of two vessel-targeting drugs against new blood vessels
      compared with mature blood vessels. These findings suggest a high potential value
      in targeting the process of angiogenesis in the treatment of children with
      retinoblastoma.

PMID- 17525174
TI  - Laminin beta1 and gamma1 containing laminins are essential for basement membrane
      integrity in the zebrafish eye.
AB  - PURPOSE: In this study recessive zebrafish mutations in the genes encoding
      laminin beta1 (lamb1) and laminin gamma1 (lamc1) were used to determine the
      functions of these laminin proteins during ocular basement membrane formation and
      during zebrafish eye development. METHODS: Ocular defects in lamb1 and lamc1
      mutants were characterized by using a combination of histology,
      immunohistochemistry, in situ hybridization, and transmission electron
      microscopy. RESULTS: The results demonstrated that zebrafish lamb1 and lamc1
      mutants possess defects in two ocular basement membranes--the lens capsule and
      the inner limiting membrane--whereas Bruch's membrane is largely unaffected.
      lamb1 and lamc1 mutants possess severe lens dysplasias that result from a
      compromise in lens capsule integrity. Inner limiting membrane continuity is
      irregular in these mutants, and these irregularities result in small retinal
      ectopias that extend from the retina into the interstitial space between the
      retina and the lens. At late embryonic stages (e.g., 5-7 days after
      fertilization), retinal lamination defects are also observed in a subset of
      laminin mutants. CONCLUSIONS: The results demonstrate that laminin beta1 and 
      gamma1 containing laminins are essential for the integrity of the lens capsule
      basement membrane and inner limiting membrane in the zebrafish eye.

PMID- 17525175
TI  - Coexpression and interaction of wild-type and missense RS1 mutants associated
      with X-linked retinoschisis: its relevance to gene therapy.
AB  - PURPOSE: X-linked retinoschisis (XLRS) is an early-onset retinal disease caused
      by mutations in retinoschisin (RS1), a multisubunit, extracellular protein
      implicated in retinal cell adhesion. Delivery of the normal RS1 gene to
      photoreceptors of retinoschisin-deficient mice results in prolonged protein
      expression and rescue of retinal structure and function. However, most persons
      with XLRS harbor a missense mutation in the RS1 gene leading to expression of a
      nonfunctional protein. The purpose of this study was to examine the effect that
      coexpression of wild-type RS1 with disease-causing mutants has on RS1 expression,
      oligomerization, and secretion to further evaluate gene therapy as a possible
      treatment for XLRS. METHODS: RS1 mutants (C59S, D158N, C142W, C142S, T185K,
      R141H, R141G) were individually expressed or coexpressed with myc-tagged wild
      type RS1 (myc-RS1) in EBNA293 cells. Protein expression, secretion, and subunit
      assembly of wild-type and mutant RS1 were analyzed by Western blotting and
      coimmunoprecipitation. Immunofluorescence was used to examine the cellular
      distribution of RS1. RESULTS: Myc-RS1 was identical to untagged, wild-type RS1
      with respect to cellular localization, disulfide-linked octamer formation, and
      secretion. In coexpression studies, myc-RS1 assembled into a disulfide-linked
      octameric complex and was secreted from cells independent of all disease-linked
      RS1 mutants studied except the R141H mutant. CONCLUSIONS: When wild-type RS1 is
      expressed in the same cells as disease-causing mutants, the wild-type protein
      undergoes protein folding, subunit assembly, and secretion independent of all
      disease-causing RS1 mutants studied except R141H. These studies suggest that gene
      therapy may be an effective treatment for most persons with XLRS.

PMID- 17525176
TI  - A novel CACNA1F gene mutation causes Aland Island eye disease.
AB  - PURPOSE: Aland Island eye disease (AIED), also known as Forsius-Eriksson
      syndrome, is an X-linked recessive retinal disease characterized by a combination
      of fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism,
      protan color vision defect, progressive myopia, and defective dark adaptation.
      Electroretinography reveals abnormalities in both photopic and scotopic
      functions. The gene locus for AIED has been mapped to the pericentromeric region
      of the X-chromosome, but the causative gene is unknown. The purpose of this study
      was to identify the mutated gene underlying the disease phenotype in the original
      AIED-affected family. METHODS: All exons of the CACNA1F gene were studied by DNA
      sequencing. CACNA1F mRNA from cultured lymphoblasts was analyzed by RT-PCR and
      cDNA sequencing. RESULTS: A novel deletion covering exon 30 and portions of
      flanking introns of the CACNA1F gene was identified in patients with AIED.
      Results from expression studies were consistent with the DNA studies and showed
      that mRNA lacked exon 30. The identified in-frame deletion mutation is predicted
      to cause a deletion of a transmembrane segment and an extracellular loop within
      repeat domain IV, and consequently an altered membrane topology of the encoded
      alpha1-subunit of the Ca(v)1.4 calcium channel. CONCLUSIONS: Mutations in CACNA1F
      are known to cause the incomplete form of X-linked congenital stationary night
      blindness (CSNB2). Since the clinical picture of AIED is quite similar to CSNB2,
      it has long been discussed whether these disorders are allelic or form a single
      entity. The present study clearly indicates that AIED is also caused by a novel
      CACNA1F gene mutation.

PMID- 17525177
TI  - A complex expression pattern of Pax6 in the pigeon retina.
AB  - PURPOSE: The retina of some avian species contains two macular regions, making it
      an excellent model for retinal, and especially macular, development. Previous
      studies have provided evidence of the involvement of Pax6 in macular development.
      The purpose was to perform a comprehensive expression analysis of Pax6 isoforms
      in different regions of the pigeon retina. METHODS: The different mRNA
      transcripts were amplified by RT-PCR and characterized by sequencing analysis.
      Semiquantitative PCR and quantitative real-time PCR analyses were used to study
      the level of expression of each transcript. Western blot analysis was performed
      on both the cytosolic and nuclear cell fractions. RESULTS: An evolutionary
      analysis of all human-chicken retinal homologues revealed that Pax6 is one of the
      most conserved retinal genes. By alternative splicing and alternative initiation
      of transcription, Pax6 produces 41 different mRNA transcripts, encoding 17
      protein isoforms in the pigeon retina, five of which are paired-less cytosolic
      proteins. Semiquantitative expression analysis revealed that the short, paired
      less, transcripts have a relatively high level of expression. Quantitative real
      time PCR analysis of the central macula, red area, and peripheral retina revealed
      a spatial and temporal expression profile indicating that many Pax6 transcripts
      take a part in macular development. CONCLUSIONS: These data suggest that Pax6, a
      highly conserved gene, can maintain evolutionarily conserved variability at the
      protein level by alternative splicing and initiation mechanisms, allowing it to
      perform multiple functions. The variability in the length of the paired domain
      suggests that the different Pax6 isoforms activate different sets of genes.

PMID- 17525179
TI  - Ethnic differences in the impact of parental myopia: findings from a population
      based study of 12-year-old Australian children.
AB  - PURPOSE: To examine the influences of ethnicity, parental myopia, and near work
      on spherical equivalent refraction (SER) and axial length (AL) in a population
      based sample of 12-year-old Australian children. METHODS: Year-7 children in the
      Sydney Myopia Study (n = 2353, 75.3% response) underwent an ophthalmic
      examination including cycloplegic autorefraction (1% cyclopentolate) and ocular
      biometry (IOLMaster; Carl Zeiss Meditec GmbH, Jena, Germany). Data for parental
      myopia, ethnicity, near work, and outdoor activities were derived from
      questionnaires and were available for 1781 children. Optical prescriptions of
      parents were sought if the spectacles were used. RESULTS: The prevalence of
      myopia in the children increased with the number of myopic parents (7.6%, 14.9%,
      and 43.6% for no, one, or two myopic parents). In parallel, the mean SER (+/-SE
      of the mean) was more negative (0.70 +/- 0.08, 0.34 +/- 0.09, and -0.55 +/- 0.34
      D), and the mean AL was longer (23.32 +/- 0.05, 23.44 +/- 0.06, and 23.62 +/-
      0.16 mm) after adjustment for demographic and environmental factors. In
      multivariate analyses, odds of childhood myopia did not change with higher levels
      of near work (odds ratio [OR] = 1.01; 95% confidence interval [CI] = 0.99-1.03).
      Interactions between parental myopia and ethnicity were significant for SER and
      AL (both P < 0.0001), reflecting greater decreases in SER and greater increases
      in AL with the number of myopic parents in the children of East Asian ethnicity
      than in the children of European Caucasian ethnicity. In the nonmyopic children,
      there was no association between parental myopia and AL. CONCLUSIONS: In this
      sample, parental myopia was associated with more myopic SER and longer AL, with
      significant ethnic interactions.

PMID- 17525178
TI  - Refractive error, axial length, and relative peripheral refractive error before
      and after the onset of myopia.
AB  - PURPOSE: To evaluate refractive error, axial length, and relative peripheral
      refractive error before, during the year of, and after the onset of myopia in
      children who became myopic compared with emmetropes. METHODS: Subjects were 605
      children 6 to 14 years of age who became myopic (at least -0.75 D in each
      meridian) and 374 emmetropic (between -0.25 D and +1.00 D in each meridian at all
      visits) children participating between 1995 and 2003 in the Collaborative
      Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Axial
      length was measured annually by A-scan ultrasonography. Relative peripheral
      refractive error (the difference between the spherical equivalent cycloplegic
      autorefraction 30 degrees in the nasal visual field and in primary gaze) was
      measured using either of two autorefractors (R-1; Canon, Lake Success, NY [no
      longer manufactured] or WR 5100-K; Grand Seiko, Hiroshima, Japan). Refractive
      error was measured with the same autorefractor with the subjects under
      cycloplegia. Each variable in children who became myopic was compared to age-,
      gender-, and ethnicity-matched model estimates of emmetrope values for each
      annual visit from 5 years before through 5 years after the onset of myopia.
      RESULTS: In the sample as a whole, children who became myopic had less hyperopia
      and longer axial lengths than did emmetropes before and after the onset of myopia
      (4 years before through 5 years after for refractive error and 3 years before
      through 5 years after for axial length; P < 0.0001 for each year). Children who
      became myopic had more hyperopic relative peripheral refractive errors than did
      emmetropes from 2 years before onset through 5 years after onset of myopia (P <
      0.002 for each year). The fastest rate of change in refractive error, axial
      length, and relative peripheral refractive error occurred during the year before
      onset rather than in any year after onset. Relative peripheral refractive error
      remained at a consistent level of hyperopia each year after onset, whereas axial
      length and myopic refractive error continued to elongate and to progress,
      respectively, although at slower rates compared with the rate at onset.
      CONCLUSIONS: A more negative refractive error, longer axial length, and more
      hyperopic relative peripheral refractive error in addition to faster rates of
      change in these variables may be useful for predicting the onset of myopia, but
      only within a span of 2 to 4 years before onset. Becoming myopic does not appear
      to be characterized by a consistent rate of increase in refractive error and
      expansion of the globe. Acceleration in myopia progression, axial elongation, and
      peripheral hyperopia in the year prior to onset followed by relatively slower,
      more stable rates of change after onset suggests that more than one factor may
      influence ocular expansion during myopia onset and progression.

PMID- 17525180
TI  - The inheritance of peripapillary atrophy.
AB  - PURPOSE: To estimate the relative importance of genes and environment in
      peripapillary atrophy type beta (beta-PPA) in a classic twin study. METHODS:
      Female twin pairs (n = 506) aged 49 to 79 years were recruited from the St.
      Thomas' UK Adult Twin Registry. Peripapillary atrophy was identified from masked
      grading of stereoscopic optic disc photographs. Structural equation modeling was
      performed using Mx with polychoric correlations of beta-PPA and refractive error
      (divided into deciles). RESULTS: Beta-PPA prevalence was 25.1% and did not vary
      with zygosity. Case-wise concordance for right eyes was 0.76 (95% CI, 0.57-0.88)
      for monozygotic (MZ) and 0.37 (95% CI, 0.15-0.56) for dizygotic (DZ) pairs.
      Multivariate modeling suggested additive genetic effects and individual
      environment, with no shared environment or dominant genetic effect. Beta-PPA
      heritability was 0.70 (95% CI, 0.54-0.83), and spherical equivalent 0.88 (95% CI,
      0.85-0.91); age had no significant effect on variance. The genetic correlation
      between beta-PPA and spherical equivalent was -0.21. However, only 3% of the
      genetic variance of beta-PPA was explained by genetic factors in common with
      refractive error, with 67% explained by specific genetic factors for beta-PPA. Of
      the 30% of variance explained by unique environmental factors, only 3% was
      explained by these factors in common with environmental factors involved in
      refractive error. CONCLUSIONS: The presence of beta-PPA, a frequent ocular
      finding known to be associated with open-angle glaucoma, appears to be under
      strong genetic control, with only a small amount of this genetic effect shared
      with genes involved in myopia.

PMID- 17525181
TI  - Corneal virulence of Candida albicans strains deficient in Tup1-regulated genes.
AB  - PURPOSE: To evaluate the role of rbt genes downstream of Tup1p, a transcription
      factor regulating fungal filamentation, in experimental Candida albicans
      keratitis. METHODS: Corneas of BALB/c mice were scarified and topically
      inoculated with 10(5) or 10(6) colony-forming units (CFU) of a wild-type human
      isolate of C. albicans (SC5314), a mutant strain with a transposon-induced
      homozygous disruption of the rbt1 gene (Tn7-rbt1), its control (DAY286),
      homozygous rbt knockout mutants deficient in rbt1 (BCa7-4) or rbt4 (BCa11-3), or
      their parental control (CAF2-1). Eyes were scored daily for clinical severity of
      fungal keratitis and were examined histopathologically. RESULTS: With a 10(5) CFU
      inoculum, the CAF2-1 control and its mutant derivatives (BCa7-4 and BCa11-3)
      produced significantly lower keratitis scores than did the moderately severe
      keratitis induced by control strains SC5314 and DAY286 and the Tn7-rbt1 mutant (P
      < 0.05). At a 10(6) CFU inoculum, all strains induced severe disease except for
      the rbt4-deficient mutant. Fungal keratitis caused by Tn7-rbt1 was as severe as
      that of control strains (P > 0.2), and the BCa7-4 mutant initially caused severe
      disease that gradually waned (P < 0.02). However, the BCa11-3 mutant produced
      moderate disease that was significantly less severe than that induced by control
      strains (P < 0.04) and resolved within 1 week. CONCLUSIONS: The rbt4 gene of C.
      albicans is a potential virulence factor in posttraumatic corneal infection.
      Genetically regulated hyphal morphogenesis appears to be involved in the initial
      pathogenesis of experimental keratomycosis.

PMID- 17525182
TI  - Role of corneal elasticity in damping of intraocular pressure.
AB  - PURPOSE: To determine corneal elasticity and its contribution in damping acute
      intraocular pressure spikes. METHODS: Twenty corneas with intact scleral rims
      were excised from human donor eyes and mounted on an artificial anterior chamber.
      A watertight seal was obtained with 17 corneas. Saline was infused into the
      chamber at a rate of 10 mL/h, and subsequent changes in pressure were measured to
      generate a pressure-volume relationship. Real-time anterior segment OCT was used
      to measure the change in radius of curvature and corneal thickness in nine eyes.
      RESULTS: The pressure-versus-volume curves of all corneal-scleral buttons were
      concave-up asymptotes, demonstrating elasticity. The range of the slope was 0.34
      to 1.6 +/- 0.29 mm Hg/microL. The mean change in the radius of curvature in the
      nine eyes that were visualized by optical coherence tomography (OCT) was 247 +/-
      106 microm (range, 168-412 microm). The OCT image was centered on the epithelial
      surface. In two eyes, the entire cornea was visible by OCT throughout the course
      of the experiment, and corneal thickness was measured and found to decrease by
      116 +/- 4 microm. CONCLUSIONS: Human eye bank corneas demonstrate elasticity ex
      vivo, with expansion and thinning in response to increases in anterior chamber
      pressure. These elastic properties may serve as a buffering mechanism for
      microvolumetric changes in the eye, thus protecting the eye from intraocular
      pressure surges in vivo.

PMID- 17525183
TI  - Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and
      lymphangiogenesis.
AB  - PURPOSE: To analyze whether bevacizumab can inhibit inflammatory angiogenesis and
      lymphangiogenesis in the cornea. Bevacizumab (Avastin; Roche, Welwyn Garden City,
      UK) is a recombinant, humanized, monoclonal antibody against VEGF-A that has been
      approved by the U.S. Food and Drug Administration for the treatment of colon
      carcinomas. METHODS: The mouse model of suture-induced corneal neovascularization
      was used to assess the antihemangiogenic and antilymphangiogenic effect of
      bevacizumab by systemic and topical application. Corneal flatmounts were stained
      with LYVE-1 as a specific lymphatic vascular endothelial marker and CD31 as a pan
      endothelial marker, and blood and lymph vascularized areas were analyzed
      morphometrically. The inhibitory effect of bevacizumab on lymphatic endothelial
      cells (LECs) was analyzed with a colorimetric (BrdU) proliferation ELISA. The
      binding ability of bevacizumab to murine VEGF-A was analyzed by Western blot,
      ELISA, and surface plasmon resonance. RESULTS: The systemic and topical
      applications of bevacizumab significantly inhibited the outgrowth of blood (P <
      0.006 and P < 0.0001, respectively) and lymphatic (P < 0.002 and P < 0.0001,
      respectively) vessels. Inhibition of the proliferation of LECs was also
      significant (P < 0.0001). Western blot analysis, ELISA, and the surface plasmon
      resonance assay showed that bevacizumab binds murine VEGF-A. CONCLUSIONS: Topical
      or systemic application of bevacizumab inhibits both inflammation-induced
      angiogenesis and lymphangiogenesis in the cornea. This finding suggests an
      important role of VEGF-A in corneal lymphangiogenesis. Bevacizumab may be useful
      in preventing immune rejections after penetrating keratoplasty or tumor
      metastasis via lymphatic vessels.

PMID- 17525184
TI  - Dry eye-induced conjunctival epithelial squamous metaplasia is modulated by
      interferon-gamma.
AB  - PURPOSE: To investigate the role of interferon (IFN)-gamma in the pathogenesis of
      conjunctival squamous metaplasia in dry eye. METHODS: Experimental dry eye was
      created by subjecting C57BL/6 and IFN-gamma-knockout mice to desiccating
      environmental stress for 5 or 10 days. T-cell antigens and IFN-gamma were
      detected by immunohistochemistry. Goblet cells were counted in periodic acid
      Schiff (PAS)-stained sections. Expression of small, proline-rich protein (SPRR)-2
      was evaluated by confocal microscopy. Tear IFN-gamma was measured by immunobead
      assay. RESULTS: Dry eye promoted migration of CD4+ T cells and IFN-gamma+ cells
      into goblet cell zones of the conjunctiva and increased the concentration of IFN
      gamma in tears. This migration was accompanied by progressive goblet cell loss
      and an increase in SPRR-2 expression in the conjunctival epithelium. A
      significant inverse correlation was observed between the density of infiltrating
      CD4+ T cells and goblet cells. Dry eye had no effect on conjunctival goblet cell
      density in IFN-gamma-knockout mice; however, exogenous administration of IFN
      gamma significantly decreased goblet cell density after 5 days. CONCLUSIONS:
      Conjunctival epithelial response to experimental dryness is related to the degree
      of CD4+ T-cell infiltration and the level of IFN-gamma production. These findings
      suggest that IFN-gamma plays a pivotal role in promoting conjunctival squamous
      metaplasia in dry eye, and they provide insight into the immune pathogenesis of
      keratoconjunctivitis sicca.

PMID- 17525185
TI  - Expression of Th-1 chemokines and chemokine receptors on the ocular surface of
      C57BL/6 mice: effects of desiccating stress.
AB  - PURPOSE: To evaluate the effects of desiccating ocular surface stress on the
      expression of chemokines and their receptors by the corneal epithelium and
      conjunctiva of C57BL/6 and BALB/c mice. METHODS: Experimental dry eye was created
      in C57BL/6 and BALB/c mice. The concentrations of macrophage inflammatory protein
      1alpha (MIP-1alpha), MIP-1beta, monokine induced by interferon (MIG)-gamma, and
      interferon-gamma-inducible protein (IP)-10 in the corneal epithelia and
      conjunctiva were measured by a multiplex immunobead assay. Expression of MIP
      1alpha; MIP-1beta; regulated on activation, normal T-cell expressed and secreted
      (RANTES), MIG, IP-10; monocyte chemoattractant protein (MCP)-3; eotaxin-1; CCR5;
      CXCR3; and CCR3 in the cornea and conjunctiva were evaluated by real-time PCR and
      immunostaining. RESULTS: Desiccating stress significantly increased
      concentrations of MIP-1alpha, MIP-1beta, IP-10, and MIG proteins in the corneal
      epithelium and conjunctiva of C57BL/6 mice. Furthermore, it increased levels of
      MIP-1alpha, MIP-1beta, and CCR5 transcripts in the cornea and conjunctiva and
      RANTES, MIG, IP-10, and CXCR3 transcripts in the conjunctiva of C57BL/6 mice. In
      contrast, levels of MCP-3, eotaxin-1, and CCR3 transcripts increased in both
      tissues of BALB/c mice. In situ immunodetection of chemokines and their receptors
      was similar to their pattern of gene expression. CONCLUSIONS: Specific patterns
      of Th-1 and -2 chemokines and their receptors are induced in the mouse ocular
      surface by desiccating stress in a strain-related fashion. Desiccating stress
      potently stimulates the expression of Th-1 cell-attracting chemokines and
      chemokine receptors on the ocular surface of C57BL/6 mice.

PMID- 17525186
TI  - Comparison of goblet cell density after femtosecond laser and mechanical
      microkeratome in LASIK.
AB  - PURPOSE: To study the effect of the LASIK procedure performed with a femtosecond
      laser and a manual microkeratome on the conjunctival goblet cell and epithelial
      cell populations. METHODS: In this prospective, nonrandomized, masked study, 64
      eyes undergoing LASIK were included: 30 with the Moria M2 (M2) microkeratome and
      34 with the IntraLase femtosecond laser (IL). The preoperative spherical
      equivalent was -2.0 +/- 3.8 D in the M2 group and -3.1+/- 3.1 D in the IL group.
      The time that the suction ring was applied on the eye was registered, and goblet
      cell density (GCD), epithelial cell morphology, and inflammatory cells were
      evaluated by conjunctival impression cytology, before and after the surgery.
      RESULTS: All the patients in both groups showed a decrease in GCD after LASIK (P
      < 0.001) that recovered after 6 months. At 1 week, 1 month, and 3 months, GCD was
      lower with IL than with M2 (P < 0.019, P < 0.001, and P < 0.024, respectively).
      The mean period that the suction ring was applied was longer in the IL than in
      the M2 group (P < 0.001). There was a high correlation between the decrease in
      GCD and the suction time (R = 0.8), and the preoperative spherical equivalent (R
      congruent with 0.4). CONCLUSIONS: Impression cytology showed a greater reduction
      in goblet cell populations after IL than after M2, probably because of the length
      of time that the suction ring exerted pressure on the conjunctiva. These changes
      in the goblet cells may contribute to the development of the ocular surface
      syndrome after LASIK procedures.

PMID- 17525187
TI  - Horizontal rectus muscle anatomy in naturally and artificially strabismic
      monkeys.
AB  - PURPOSE: Structural abnormalities of extraocular muscles (EOMs) or their pulleys
      are associated with some forms of human strabismus. This experiment was conducted
      to investigate whether such abnormalities are associated with artificial or
      naturally occurring strabismus in monkeys. METHODS: Binocular alignment and
      grating visual acuities were determined in 10 monkeys representing various
      species using search coil recording and direct observations. Four animals were
      orthotropic, two had naturally occurring "A"-pattern esotropia, two had
      concomitant and one had "V"-pattern esotropia artificially induced by alternating
      or unilateral occlusion in infancy, and one had "A"-pattern exotropia
      artificially induced by prism wear. After euthanasia, 16 orbits were examined by
      high-resolution magnetic resonance imaging (MRI) in the quasi-coronal plane.
      Paths and sizes of horizontal rectus EOMs were analyzed quantitatively in a
      standardized coordinate system. Whole orbits were then serially sectioned en bloc
      in the quasi-coronal plane, stained for connective tissue, and compared with MRI.
      Nerve and EOM features were analyzed quantitatively. RESULTS: Quantitative
      analysis of MRI revealed no significant differences in horizontal rectus EOM
      sizes or paths among orthotropic or naturally or artificially strabismic monkeys.
      Histologic examination demonstrated no differences in EOM size, structure, or
      innervation among the three groups, and no differences in connective tissues in
      the pulley system. The accessory lateral rectus (ALR) EOM was present in all
      specimens, but was small, inconsistently located, and sparsely innervated.
      Characteristics of the ALR did not correlate with strabismus. CONCLUSIONS: Major
      structural abnormalities of horizontal rectus EOMs and associated pulleys are
      unrelated to natural or artificial horizontal strabismus in the monkeys studied.
      The ALR is unlikely to contribute to horizontal strabismus in primates. However,
      these findings do not exclude a possible role of pulley abnormalities in
      disorders such as cyclovertical strabismus.

PMID- 17525188
TI  - Modeling dose-response in amblyopia: toward a child-specific treatment plan.
AB  - PURPOSE: This article describes an empirically derived mathematical model of the
      treatment dose-response of occlusion therapy for amblyopia based on outcome data
      obtained from the Monitored Occlusion Treatment for Amblyopia Study (MOTAS).
      METHODS: The MOTAS protocol comprised three discrete phases: baseline, refractive
      adaptation, and occlusion. Only data from the occlusion phase were used in this
      dose-response model. Seventy-two participants, 3 to 8 years of age, mean +/- SD
      age 5.2 +/- 1.4 years (anisometropia [n = 18]); strabismus [n = 22]); both
      anisometropia and strabismus [n = 32]) completed the occlusion phase. All
      participants were prescribed 6-h/d patching, which was objectively monitored by
      an occlusion dose monitor (ODM). RESULTS: Simple normal linear regression
      modeling of the data on an interval-by-interval basis (interval between clinic
      visits) indicates that increasing cumulative dose within interval (hours) yields
      an increase in visual acuity (R2 = 0.918; 684 data points). Most of the children
      achieved their best visual acuity with 150 to 250 hours' cumulative dose.
      Specific patient characteristics (especially age) modify the steepness of this
      function. For example, a 0.20-logMAR (2-line logarithm of the minimum angle of
      resolution) gain in visual acuity requires a cumulative dose of 170 hours for
      children at age 48 months and 236 hours at age 72 months. CONCLUSIONS:
      Mathematical modeling of amblyopia therapy is a novel approach that elucidates
      the kinetics of the therapeutic response in humans. This response is age
      influenced so that older children require a greater dose to achieve the same
      outcome--evidence of altered plasticity of the visual system. Fine-tuning the
      dose-response in amblyopia therapy will facilitate the development of child
      specific, evidence-based treatment plans.

PMID- 17525189
TI  - Oculomotor control in children who were born very prematurely.
AB  - PURPOSE: Preterm infants are at increased risk of a variety of cerebral lesions,
      involving the white matter, cortex, cerebellum, thalamus, and caudate nucleus,
      many of which could compromise the control of eye movement. Visual problems and
      disorders of binocularity and alignment have been reported, but little if any
      quantitative assessment of oculomotor control has been undertaken. The purpose of
      this study was to extend the initial pilot study and quantitatively examine the
      control of saccades, smooth pursuit, and antisaccades in children who were born
      very prematurely. METHODS: A group of preterm (PT) children aged 8 to 11 years
      (<32 weeks' gestation), who had normal IQ (>or=85) and were free of major
      disabilities (cerebral palsy, blindness, or deafness), and full-term (FT) control
      subjects of similar age were recruited from a geographically defined cohort.
      Antisaccades were examined in 36 preterm and 33 full-term subjects and smooth
      pursuit and saccades in 21 preterm and 19 full-term subjects, by using infrared
      oculography. Saccade and antisaccade targets were presented at an amplitude of 5
      degrees according to a standard synchronous paradigm, and pursuit was assessed by
      using a step-ramp paradigm with a target velocity of 14 deg/s. RESULTS: There
      were no statistically significant differences between the preterm and the full
      term subjects in relation to saccade gain, latency, duration, peak velocity, or
      the proportion of express saccades. Smooth-pursuit latencies tended to be
      slightly longer in the preterm subjects (leftward: P = 0.17, rightward: P =
      0.02), but there were no significant differences between them and the full-term
      subjects in pursuit acceleration, open-loop velocity, or peak slow-eye velocity.
      The main area of deficit in the preterm children occurred in the voluntary
      control of saccades, with significantly higher antisaccade directional error
      rates (PT: 73.3% +/- 18.1%, FT: 54.2% +/- 16.9%, mean +/- SD; P < 0.001). The
      latency of the antisaccade error tended to be shorter in preterm subjects (P =
      0.065), with a greater proportion of errors with latency in the express range (P
      = 0.08). CONCLUSIONS: Despite the increased risk of cerebral lesions, the control
      of saccades and pursuit was largely normal in the preterm children, suggesting
      that pathways at the level of the brain stem were principally intact. However,
      the preterm children had difficulties with the voluntary control of saccades,
      particularly in the area of inhibition, which may be indicative of a deficit in
      the region of the dorsolateral prefrontal cortex. This finding is consistent with
      other reports in preterm children in whom executive function has been found to be
      compromised, and both these aspects of behavior are likely to share similar areas
      of cortical control.

PMID- 17525190
TI  - Acute superior oblique palsy in monkeys: I. Changes in static eye alignment.
AB  - PURPOSE: To investigate immediate and long-term changes in static ocular
      alignment with acute acquired superior oblique palsy (SOP) in monkeys. METHODS:
      The trochlear nerve was severed intracranially in two rhesus monkeys. After the
      surgery, the paretic eye was patched for 6 to 9 days, and then binocular viewing
      was allowed. Three-axis eye movements (horizontal, vertical, and torsional) were
      measured with binocular, dual search coils. Eye movements were recorded over a +/
      20 degrees horizontal and vertical range of fixations before the lesion and then,
      beginning the first day after surgery. Changes in alignment with +/-30 degrees
      head tilt were also studied. RESULTS: The main findings were (1) misalignment (10
      12 degrees vertical in adduction, down; 10-12 degrees torsional in abduction,
      down); (2) changes in vertical deviation (VD) with head tilt (Delta 2-6 degrees
      with left versus right 30 degrees tilt); and (3) changes in comitance and VD over
      time. During the early postlesion period, before binocular viewing was allowed,
      VD decreased and comitance improved. Once binocular viewing was allowed, VD
      increased and comitance worsened. CONCLUSIONS: Rhesus monkeys with induced SOP
      show a characteristic pattern of misalignment that helps define the ocular motor
      signature of acute denervation of the superior oblique muscle. The animals also
      showed striking changes over time in the amount and comitance of the vertical
      misalignment that depended on whether viewing was monocular or binocular,
      suggesting a role for proprioception in adaptation to misalignment with habitual
      monocular viewing.

PMID- 17525191
TI  - Acute superior oblique palsy in monkeys: II. Changes in dynamic properties during
      vertical saccades.
AB  - PURPOSE: To investigate vertical and torsional eye motion during and immediately
      after vertical saccades with acute acquired superior oblique palsy (SOP) in
      monkeys. METHODS: The trochlear nerve was severed intracranially in two rhesus
      monkeys. After surgery, the paretic eye was patched for 6 to 9 days, and then
      binocular viewing was allowed. Three-axis eye movements (horizontal, vertical,
      and torsion) were measured with binocular, dual search coils. Eye movements were
      recorded before surgery and then beginning 2 to 3 days after surgery during 20
      degrees vertical saccades over a +/-20 degrees horizontal and vertical range.
      RESULTS: The main findings were: (1) Saccade amplitude in the paretic eye (PE)
      was smaller than that of the normal eye (NE), especially for downward saccades
      with the PE in adduction; (2) vertical drift was backward after upward saccades
      with the PE in adduction or abduction, onward after downward saccades with the PE
      in adduction, but backward for downward saccades with the PE in abduction, drift
      time constants averaged 35 ms; (3) peak dynamic blip intrasaccadic torsion
      increased (relative extorsion), the most for upward saccades with the PE in
      abduction; (4) postsaccadic torsional drift increased (relative intorsion), the
      most for downward saccades with the PE in adduction; and (5) the peak velocity
      amplitude relationship in vertical saccades was little affected, but the ratio
      between the peak velocity of the two eyes was a consistent indicator of the
      palsy. CONCLUSIONS: Rhesus monkeys with acute acquired SOP show characteristic
      changes in vertical and torsional movements during and immediately after vertical
      saccades that help define the ocular motor signature of denervation of the SO
      muscle. These dynamic changes were largely unrelated to the changes in static
      alignment over time, suggesting that static and dynamic disturbances in SOP are
      influenced by separate central mechanisms.

PMID- 17525192
TI  - Acute superior oblique palsy in monkeys: III. Relationship to Listing's Law.
AB  - PURPOSE: To investigate the three-dimensional orientation of the eye and its
      relationship to Listing's Law in monkeys with acute acquired superior oblique
      palsy (SOP). METHODS: The trochlear nerve was severed intracranially in two
      rhesus monkeys. Three-axis eye movements (horizontal, vertical, and torsion) were
      measured with binocular, dual search coils during fixation of targets in a 40
      degrees x 40 degrees grid. Rotation vectors were calculated, and Listing's plane
      (LP) was determined by a least-squares planar fit of eye torsion as a function of
      horizontal and vertical position. RESULTS: The main findings were: (1) In the
      paretic eye, there was an immediate and sustained rotation of the orientation
      plane by approximately 25 degrees in the temporal direction; (2) the thickness of
      LP, defined as the torsional standard deviation (SD), increased little (by 0.13
      degrees in M1 and 0.08 degrees in M2) after SOP, and (3) the SD of intrasaccadic
      torsion was slightly greater than that during fixation, but there was no change
      after SOP. CONCLUSIONS: Acute SOP in rhesus monkeys leads to a temporal rotation
      of LP. This is consistent with a relatively increased extorsion in down gaze due
      to a loss of normal intorsion by the superior oblique muscle. The SD of torsion
      increased by only a small amount, implying that the validity of Listing's Law is
      not affected much by complete SOP, despite the large change in the orientation of
      LP.

PMID- 17525193
TI  - Luminance-modulated adaptation of global flash mfERG: fellow eye losses in
      asymmetric glaucoma.
AB  - PURPOSE: To use the global flash multifocal electroretinogram (mfERG) in patients
      with asymmetric glaucoma to determine whether retinal function is affected in
      fellow eyes that have no glaucomatous visual field defects. METHODS: Forty normal
      subjects and 12 patients with asymmetric glaucoma were recruited for visual field
      and mfERG measurement. The mfERG was assessed by using a global-flash stimulation
      paradigm with four video frames: 103 scaled hexagonal elements followed by a dark
      frame, a global-flash frame, and a dark frame. The localized luminance difference
      was set at 96%, 65%, 49%, and 29% display contrast during the four different test
      conditions, respectively. The first-order kernel response was measured, and the
      "adaptive index" which has been used previously was calculated. RESULTS: In
      fellow eyes with normal visual fields, the amplitude of the induced component
      (IC) was significantly reduced, and the adaptive index was reduced by a factor of
      almost 10 (P < 0.0001), as it was in the glaucomatous eyes. Although the adaptive
      index in the better (fellow) eye of the patients with glaucoma was slightly
      higher than in the eyes with diagnosed glaucoma, these differences were not
      statistically significant. CONCLUSIONS: The significant reduction of the adaptive
      index in the better eyes in subjects with asymmetric glaucoma shows that the fast
      adaptive mechanism(s) were reduced in these eyes. This implies that eyes that
      have functionally normal visual acuity and visual fields have abnormal fast
      adaptive mechanisms.

PMID- 17525194
TI  - Synergism of TNF and IL-1 in the induction of matrix metalloproteinase-3 in
      trabecular meshwork.
AB  - PURPOSE: TNF and IL-1 increase matrix metalloproteinase-3 (MMP-3) expression in
      the trabecular meshwork (TM). TNF-alpha, in combination with IL-1alpha or IL
      1beta, produces highly synergistic MMP-3 increases. Possible mechanisms for this
      synergism in TM cells were investigated. METHODS: Porcine and human TM cells were
      treated with TNF-alpha, IL-1alpha, IL-1beta and their combinations. Western
      immunoblots were used to evaluate MMP-3, MMP-9, MMP-12, TNF-alpha, IL-1alpha, IL
      1beta, IL-6, TNF receptor I (RI), IL-1 RI, and IL-1 RII levels and the
      phosphorylation of Erk, JNK, and p38 MAP kinases. Dose-response effects for TNF
      alpha, IL-1alpha and IL-1beta on MMP-3 were evaluated. Microarray and
      quantitative RT-PCR were used to determine mRNA levels. MMP-3 transcription rate
      was assessed by transfecting TM cells with an MMP-3 promoter/reporter construct.
      Combined cytokine effects on outflow facility were appraised in perfused anterior
      segment organ culture. RESULTS: TNF-alpha, IL-1alpha, and IL-1beta each
      individually increased MMP-3 levels, whereas TNF-alpha in combination with IL
      1alpha or IL-1beta produced highly synergistic increases. MMP-9 and MMP-12 levels
      were also elevated, but only MMP-12 showed synergism. IL-1alpha, IL-1beta, and IL
      6, but not TNF-alpha mRNA or protein level, were elevated by these cytokines.
      Maximum MMP-3 production for individual cytokines, even at high doses, was far
      less than with dual cytokine doses. Erk 1 and 2, JNK 1 and 2, and p38 alpha and
      beta phosphorylation increased, but not synergistically. However, phosphorylation
      of novel isoforms of JNK and p38 delta and gamma did show synergism. MMP-3 mRNA
      levels and transcription rates also demonstrated synergism. TNF-alpha
      significantly increased IL-1 RI levels. Synergism in outflow facility was
      observed with TNF-alpha and IL-1alpha. CONCLUSIONS: TNF-alpha, in combination
      with IL-1alpha or IL-1beta, produced intense synergistic increases in MMP-3 and
      MMP-12 but not in MMP-9. Induction of IL-1 RI by TNF-alpha partially explains the
      synergism. Responses of novel JNK and p38 MAP kinase delta and gamma isoforms
      also partially account for the synergism. Understanding this strong synergistic
      effect may provide useful insight into optimizing therapeutic regulation of
      intraocular pressure in glaucoma.

PMID- 17525195
TI  - American Chinese glaucoma imaging study: a comparison of the optic disc and
      retinal nerve fiber layer in detecting glaucomatous damage.
AB  - PURPOSE: To compare the relationships between optic nerve structural measures and
      visual function, as well as the diagnostic sensitivity for glaucoma detection
      between the retinal nerve fiber layer (RNFL) and neuroretinal rim measurements.
      METHODS: A total of 101 normal and 156 glaucomatous eyes of 257 enrolled subjects
      were examined. RNFL thickness was measured by optical coherence tomography, and
      the neuroretinal rim (rim area, rim/disc area, and rim volume) was measured with
      a confocal scanning laser ophthalmoscope. The relationship between the structural
      measures and visual field sensitivity was evaluated with linear and non-linear
      regression (quadratic and logarithmic) models. The coefficient of determination
      (R2) was calculated, and the regression models were compared with Alkaike's
      information criteria and the F test. The diagnostic sensitivity for glaucoma
      detection in each structural measure was determined by the area under the
      receiver operating characteristic curve (AUC). RESULTS: The relationship of the
      RNFL, rim area, rim/disc area, and rim volume with visual function was best
      described with nonlinear regression models (quadratic regression for the RNFL [R2
      = 0.383]), rim area [R2 = 0.303]), and rim/disc area [R2 = 0.265]; and
      logarithmic regression for rim volume [R2 = 0.175]). The change of visual
      sensitivity at each level of structural damage was highest for the RNFL. The AUC
      for the RNFL also was higher than the neuroretinal rim measures. In this study
      population, at 90% specificity, the diagnostic sensitivities for detecting
      glaucomatous damage was 82.7%, 67.3%, 67.3%, and 52.6% for the RNFL, rim area,
      rim/disc area, and rim volume, respectively. (These values would apply only to a
      group with inclusion criteria and disease severity similar to those of the
      present cohort.) CONCLUSIONS: The RNFL showed a stronger structure-function
      association and a higher diagnostic sensitivity for glaucoma detection than did
      the neuroretinal rim.

PMID- 17525196
TI  - The effect of disc size and severity of disease on the diagnostic accuracy of the
      Heidelberg Retina Tomograph Glaucoma Probability Score.
AB  - PURPOSE: To compare the effect of disc size and disease severity on the
      Heidelberg Retina Tomograph (HRT) Glaucoma Probability Score (GPS) and the
      Moorfields Regression Analysis (MRA) for discriminating between glaucomatous and
      healthy eyes. METHODS: Ninety-nine eyes with repeatable standard automated
      perimetry results showing glaucomatous damage and 62 normal eyes were included
      from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). The
      severity of glaucomatous visual field defects ranged from early to severe
      (average [95% CI] pattern standard deviation [PSD] was 5.7 [5.0-6.5] dB). The GPS
      (HRTII ver. 3.0; Heidelberg Engineering, Heidelberg, Germany) utilizes two
      measures of peripapillary retinal nerve fiber layer shape (horizontal and
      vertical retinal nerve fiber layer curvature) and three measures of optic nerve
      head shape (cup depth, rim steepness, and cup size) as input into a relevance
      vector machine learning classifier that estimates a probability of having
      glaucoma. The MRA compares measured rim area with predicted rim area adjusted for
      disc size to categorize eyes as outside normal limits, borderline, or within
      normal limits. The effect of disc size and severity of disease on the diagnostic
      accuracy of both GPS and MRA was evaluated using the generalized estimating
      equation marginal logistic regression analysis. RESULTS: Using the manufacturers'
      suggested cutoffs for GPS global classification (>64% as outside normal limits),
      the sensitivity and specificity (95% CI) were 71.7% (62.2%-79.7%) and 82.3%
      (71.0%-89.8%), respectively. The sensitivity and specificity (95% CI) of the MRA
      result were 66.7% (58.0%-76.1%) and 88.7% (78.5%-94.34%), respectively.
      Likelihood ratios for regional GPS and MRA results outside normal limits ranged
      from 4.0 to 10.0, and 6.0 to infinity, respectively. Disc size and severity of
      disease were significantly associated with the sensitivity of both GPS and MRA.
      CONCLUSIONS: GPS tended to have higher sensitivities and somewhat lower
      specificities and lower likelihood ratios than MRA. These results suggest that in
      this population, GPS and MRA differentiate between glaucomatous and healthy eyes
      with good sensitivity and specificity. In addition, the likelihood ratios suggest
      that GPS may be most useful for confirming a normal disc, whereas MRA may be most
      helpful in confirming a suspicion of glaucoma. Larger disc size and more severe
      field loss were associated with improved diagnostic accuracy for both GPS and
      MRA.

PMID- 17525197
TI  - Cholesterol as treatment for pneumococcal keratitis: cholesterol-specific
      inhibition of pneumolysin in the cornea.
AB  - PURPOSE: The purpose of this study was to determine whether cholesterol, the host
      cell receptor for pneumolysin of Streptococcus pneumoniae, could effectively
      treat pneumococcal keratitis. METHODS: New Zealand White rabbits were
      intrastromally injected with 10(5) colony-forming units (CFUs) of S. pneumoniae
      D39. Corneas were treated with topical drops of 1% cholesterol every 2 hours
      beginning 25 hours after infection and were examined by slit lamp microscopy 24,
      36, and 48 hours after infection. Rabbits were killed, and CFUs were recovered
      from the corneas after the final slit lamp examination (SLE). Minimal inhibitory
      concentration (MIC) assays of cholesterol against bacteria were performed.
      Specific inhibition of pneumolysin by cholesterol in the rabbit cornea was tested
      by intrastromal injection of pneumolysin with or without cholesterol and was
      compared with cholesterol inhibition of pneumolysin in vitro using hemolysis
      assays with rabbit erythrocytes. RESULTS: Corneas treated with cholesterol had
      significantly lower SLE scores 48 hours after infection than corneas treated with
      vehicle (P = 0.0015). Treated corneas also had significantly less log(10) CFUs
      than vehicle-treated corneas (P = 0.0006). Cholesterol at a 1% concentration was
      bactericidal to bacteria in vitro, and lower concentrations of cholesterol were
      partially inhibitory in a concentration-dependent manner. Cholesterol also
      specifically inhibited 1 mug pneumolysin in vivo and up to 50 ng pneumolysin in
      vitro. CONCLUSIONS: Topical cholesterol is an effective treatment for S.
      pneumoniae keratitis. Cholesterol not only inhibits pneumolysin, it is also
      bactericidal.

PMID- 17525198
TI  - Suppression of established experimental autoimmune uveitis by anti-LFA-1alpha Ab.
AB  - PURPOSE: To identify costimulatory molecules that are important in the effector
      phase of experimental autoimmune uveitis (EAU). METHODS: EAU was induced in
      C57BL/6 (B6) mice by transfer of activated T cells specific for the
      interphotoreceptor-binding protein (IRBP) 1-20 peptide. The animals were then
      treated with and without anti-leukocyte function associated antigen (LFA)-1alpha
      mAb, at day 0 or 10 (disease onset) after T-cell transfer. Clinical signs of
      inflammation, ocular histology, and infiltrated inflammatory cells in the eye
      were compared. The primary and secondary proliferative responses of uveitogenic
      CD4 and CD8 T cells were tested after treatment with costimulatory blockers in
      vivo and in vitro. Moreover, the abilities of uveitogenic T cell trafficking and
      their interaction with retinal astrocytes were examined. RESULTS: Anti-LFA-1alpha
      Abs caused significant suppression of disease when administered either at the
      time of effector uveitogenic T cell transfer or at disease onset. Studies of the
      mechanisms by which anti-LFA-1alpha Ab inhibits the effector phase of uveitis
      demonstrated that it blocks multiple pathogenic events of uveitis mediated by
      IRBP-specific uveitogenic T cells, including the activation of T cells outside
      and inside the eye and the trafficking of activated autoreactive T cells into the
      inflammatory site. In addition, Ab treatment selectively suppressed the
      activation and expansion of pathogenic, but not regulatory, T cells in vivo.
      CONCLUSIONS: Anti-LFA-1alpha Abs are potent inhibitors of established autoimmune
      uveitis and that such treatment may be applicable not only for the prevention,
      but also the treatment, of T-cell-mediated autoimmune diseases.

PMID- 17525199
TI  - Unique gene expression profiles of donor-matched human retinal and choroidal
      vascular endothelial cells.
AB  - PURPOSE: Consistent with clinical observations that posterior uveitis frequently
      involves the retinal vasculature and recent recognition of vascular
      heterogeneity, the hypothesis for this study was that retinal vascular
      endothelium was a cell population of unique molecular phenotype. METHODS: Donor
      matched cultures of primary retinal and choroidal endothelial cells from six
      human cadavers were incubated with either Toxoplasma gondii tachyzoites (10:1,
      parasites per cell) or Escherichia coli lipopolysaccharide (100 ng/mL); control
      cultures were simultaneously incubated with medium. Gene expression profiling of
      endothelial cells was performed using oligonucleotide arrays containing probes
      designed to detect 8746 human transcripts. After normalization, differential gene
      expression was assessed by the significance analysis of microarrays, with the
      false-discovery rate set at 5%. For selected genes, differences in the level of
      expression between retinal and choroidal cells were evaluated by real-time RT
      PCR. RESULTS: Graphic descriptive analysis demonstrated a strong correlation
      between gene expression of unstimulated retinal and choroidal endothelial cells,
      but also highlighted distinctly different patterns of expression that were
      greater than differences noted between donors or between unstimulated and
      stimulated cells. Overall, 779 (8.9%) of 8746 transcripts were differentially
      represented. Of note, the 330 transcripts that were present at higher levels in
      retinal cells included a larger percentage of transcripts encoding molecules
      involved in the immune response. Differential gene expression was confirmed for
      12 transcripts by RT-PCR. CONCLUSIONS: Retinal and choroidal vascular endothelial
      cells display distinctive gene expression profiles. The findings suggest the
      possibility of treating posterior uveitis by targeting specific interactions
      between the retinal endothelial cell and an infiltrating leukocyte.

PMID- 17525200
TI  - Age-related cataracts in alpha3Cx46-knockout mice are dependent on a calpain 3
      isoform.
AB  - PURPOSE: Previous studies have demonstrated that in 129alpha3Cx46-/- mice, age
      related nuclear cataract is formed. In the present study, a more in vivo-relevant
      model was generated to test the hypothesis that the calpain 3 gene is involved in
      age-related nuclear cataractogenesis in alpha3Cx46 knockout mice. METHODS: To
      test the hypothesis that the calpain 3 gene is involved in age-related nuclear
      cataractogenesis in alpha3Cx46 knockout mice, 129alpha3Cx46-/- and CAPN3-/- mice
      were mated to generate homozygous double-knockout (dKO) mice. Lenses from the
      mice were examined by visual observation, laser scan analysis, and histologic and
      biochemical methods. RESULTS: In the absence of the CAPN3 gene, the formation of
      a cataract was delayed, and its appearance was changed to a more diffuse,
      pulverulent type. Unlike in the 129alpha3Cx46-/- mouse, cleavage of gamma
      crystallin was not detected in the dKO mouse. In both 129alpha3Cx46-/- and dKO
      mice, total Ca2+ increased. CONCLUSIONS: The present study shows for the first
      time that calpain 3 is necessary for the formation of age-dependent nuclear
      cataracts in alpha3Cx46-/- mice. Evidence that the calpain 3 gene is directly
      involved in, or part of the pathway that leads to, gamma-crystallin cleavage is
      presented. These results are consistent with the hypothesis that the loss of
      alpha3Cx46 leads to increased levels of Ca2+ ions, and this increase activates
      the CAPN3 isoform, Lp82/85, which results in the formation of a nuclear cataract.

PMID- 17525201
TI  - X-ray- and neutron-scattering studies of alpha-crystallin and evidence that the
      target protein sits in the fenestrations of the alpha-crystallin shell.
AB  - PURPOSE: Alpha-crystallin, a ubiquitous molecular chaperone, is found in high
      concentrations in the lens. Its structure and precise mechanism of action,
      however, are unknown. The purpose of these experiments was to further the
      understanding of the chaperone function of alpha-crystallin. METHODS: X-ray- and
      neutron-solution-scattering studies were used to measure the radius of gyration
      of bovine lens alpha-crystallin when complexed with its target protein beta
      crystallin in both normal and heavy-water-based solutions. Spectrophotometry was
      used as a chaperone assay. RESULTS: The radius of gyration of alpha-crystallin on
      its own and when mixed with beta-crystallin was 69 +/- 1 A at 35 degrees C and
      increased with the temperature. In contrast to H2O-buffered solutions, the radius
      of gyration did not increase significantly in D2O-buffered solutions up to 55
      degrees C, and at 70 degrees C was, on average, some 15 to 20 A smaller.
      CONCLUSIONS: Bovine lens alpha-crystallin in solution can be modeled as a
      fenestrated spherical shell of diameter 169 A. At physiological temperatures, a
      weak interaction between alpha- and beta-crystallin occurs, and beta-crystallin
      is located in the fenestrations. Deuterium substitution indicates that the
      superaggregation process is controlled by hydrogen bonding. However, the
      chaperone process and superaggregation appear not to be linked.

PMID- 17525202
TI  - Lens cell survival after exposure to stress in the closed capsular bag.
AB  - PURPOSE: Despite recent improvements in IOL design posterior capsule
      opacification (PCO) remains a significant clinical problem after cataract
      surgery. The Perfect Capsule device (Milvella, Ltd., Epping, Australia) permits
      the introduction and subsequent removal of potentially toxic agents into the
      closed capsular bag. The present purpose was to compare the relative
      effectiveness of exposing cells within the human capsular bag with a range of
      stresses with clinical potential and to compare the response to the same agents
      when applied to rabbit capsular bags and to cultured human lens cells. METHODS:
      Human capsular bags were prepared from donor eyes and sealed with the Perfect
      Capsule device. Distilled water, 3 M NaCl, 250 microg/mL, 25 mg/mL 5-fluorouracil
      and 100 microM thapsigargin (Tg) were introduced for 2 minutes. The bags were
      then perfused with Eagle's minimum essential medium (EMEM) and an IOL inserted
      before the bags were dissected and pinned to the base of plastic culture dishes.
      The bags were maintained in EMEM for 28 days and phase images were acquired
      throughout. Rabbit eyes were prepared and cultured in a similar manner, although
      tests were limited to 5-FU (25 mg/mL) and Tg (30-300 microM). FHL124 cells were
      cultured on plastic (EMEM supplemented with 5% FCS), and serum was removed for 24
      hours before exposure to the same agents as human bags. Cell survival was
      assessed by quantifying Coomassie blue staining after 4 days. RESULTS: Initially,
      NaCl induced by far the most obvious signs of cell death, especially of anterior
      cells, followed by 5-FU>water>Tg. However, by 2 weeks, cell death became more
      apparent in the Tg-exposed bags, and, at the end of 4 weeks, there were no cells
      surviving. Cells on the posterior capsule were confluent in water-exposed bags
      (similar to unexposed controls), whereas after NaCl exposure, coverage was
      incomplete but greater than after 5-FU. In the rabbit bags, exposure to 25 mg/mL
      5-FU totally eliminated cells, but 100 microM Tg was ineffective. At the end of a
      4-day culture of FHL124 cells exposed for 2 minutes to NaCl, 5-FU or Tg, there
      were no cells surviving, whereas there was 50% cell survival compared with
      control cells after water treatment. CONCLUSIONS: Tissue-cultured human lens
      cells are much more sensitive to short-term hyperosmotic than hyposmotic stress,
      with a rapid onset of cell death of cultured cells exposed to 3 M NaCl. This
      finding was confirmed in human capsular bags although adherent fibers appear to
      offer additional protection to 5-FU which can be overcome by the very hydrophobic
      Tg. The application of the Perfect Capsule system in concert with thapsigargin
      provides a promising means of preventing PCO.

PMID- 17525203
TI  - Transforming growth factor-beta1 represses E-cadherin production via slug
      expression in lens epithelial cells.
AB  - PURPOSE: TGFbeta is a potent candidate for epithelial-mesenchymal transition
      (EMT) during the development of anterior polar cataracts in the human lens. The
      Snail superfamily is involved in EMT through the repression of E-cadherin
      production. This study was conducted to determine whether the Snail gene family
      is activated in the process of TGFbeta1-induced EMT and how TGFbeta1 regulates
      the expression of this gene family. METHODS: Total RNA extracted from human
      cataract samples was subjected to the real-time PCR quantification of Slug mRNA.
      Induction of Slug expression by TGFbeta1 (10 ng/mL) in lens epithelial cells was
      determined by RT-PCR, immunostaining, immunoblot analysis, and Slug promoter
      analysis. A series of Slug promoter deletion constructs was used to identify the
      putative regulatory element responsive to TGF signaling. Chromatin
      immunoprecipitation was performed to determine whether Sp1 associates with the
      endogenous Slug promoter. Inhibition of Slug expression with Slug siRNA was used
      to investigate the role of Slug in TGFbeta-mediated EMT. RESULTS: Slug levels
      were highly upregulated in lens epithelial cells obtained from patients with
      anterior polar cataracts. Treatment of TGFbeta1 induced the expression of Slug in
      both lens and other epithelial cells in vitro. TGFbeta1-induced Slug expression
      was significantly inhibited by the MEK- and JNK/SAPK-specific inhibitors, but not
      by transfection with dominant-negative forms of Smads or small GTPase proteins,
      indicating that MAPK pathways are involved in the regulation of Slug expression
      by TGFbeta1. The Slug promoter analysis revealed that the Sp1 binding site in the
      Slug promoter is responsible for TGFbeta1-induced Slug expression. In addition,
      the TGFbeta1-mediated repression of E-cadherin was significantly inhibited by
      Slug siRNA. CONCLUSIONS: These data suggest that TGFbeta1 induces Slug expression
      and that the repression of E-cadherin production by TGFbeta1 is mediated by the
      induction of Slug in lens epithelial cells.

PMID- 17525204
TI  - A cholinergic agonist attenuates endotoxin-induced uveitis in rats.
AB  - PURPOSE: Investigation of physiological anti-inflammatory mechanisms can
      contribute to the treatment of inflammatory disorders. The purpose of the present
      study was to investigate the effect of nicotine, a selective cholinergic agonist,
      on endotoxin-induced uveitis (EIU) in rats and the underlying molecular
      mechanism. METHODS: Lipopolysaccharide (LPS; endotoxin) and nicotine were
      injected intraperitoneally. Clinical scores were evaluated by slit lamp.
      Intracameral protein content and the number of cells were determined.
      Immunohistochemical reactivity of alpha7 nicotine acetylcholine receptor
      (alpha7nAChR) was examined in the iris and ciliary body (ICB). mRNA and protein
      levels of cytokines and chemokines were measured by real-time PCR and enzyme
      linked immunosorbent assay. RESULTS: After LPS injection, clinical scores, as
      well as protein content and number of cells in the aqueous humor increased during
      18 to 36 hours. Nicotine inhibited the endotoxin-induced elevation of these
      levels. mRNA and protein of alpha7nAChR expression levels were significantly
      increased by LPS and/or nicotine injection. Nicotine showed no effects on
      endotoxin-induced elevation of mRNA levels in ICB. However, nicotine decreased
      the endotoxin-induced elevation of interleukin (IL)-6, IL-1beta, tumor necrosis
      factor (TNF)-alpha, cytokine-induced neutrophil chemoattractant (CINC)-1, and
      monocyte chemotactic protein (MCP)-1, but did not affect IL-10 in the serum and
      aqueous humor. CONCLUSIONS: Nicotine attenuated endotoxin-induced uveitis through
      directly decreasing the levels of multiple cytokines and chemokines in the
      aqueous humor, but did not affect the mRNA levels of these factors. The findings
      suggest that the nicotinic anti-inflammatory pathway may be involved in the
      pathogenesis of EIU.

PMID- 17525205
TI  - Nondestructive quantification of analyte diffusion in cornea and sclera using
      optical coherence tomography.
AB  - PURPOSE: Noninvasive functional imaging, monitoring, and quantification of
      analytes transport in epithelial ocular tissues are extremely important for
      therapy and diagnostics of many eye diseases. In this study the authors
      investigated the capability of optical coherence tomography (OCT) for noninvasive
      monitoring and quantification of diffusion of different analytes in sclera and
      cornea of rabbit eyes. METHODS: A portable time-domain OCT system with wavelength
      of 1310 +/- 15 nm, output power of 3.5 mW, and resolution of 25 mum was used in
      this study. Diffusion of different analytes was monitored and quantified in
      rabbit cornea and sclera of whole eyeballs. Diffusion of water, metronidazole
      (0.5%), dexamethasone (0.2%), ciprofloxacin (0.3%), mannitol (20%), and glucose
      solution (20%) were examined, and their permeability coefficients were calculated
      by using OCT signal slope and depth-resolved amplitude methods. RESULTS:
      Permeability coefficients were calculated as a function of time and tissue depth.
      For instance, mannitol was found to have a permeability coefficient of (8.99 +/-
      1.43) x 10(-6) cm/s in cornea and (6.18 +/- 1.08) x 10(-6) cm/s in sclera. The
      permeability coefficient of drugs with small concentrations (where water was the
      major solvent) was found to be in the range of that of water in the same tissue
      type, whereas permeability coefficients of higher concentrated solutions varied
      significantly. CONCLUSIONS: Results suggest that the OCT technique might be a
      powerful tool for noninvasive diffusion studies of different analytes in ocular
      tissues. However, additional methods of OCT signal acquisition and processing are
      required to study the diffusion of agents of small concentrations.

PMID- 17525206
TI  - The slower the better: on the instability of gas jets in a model of pneumatic
      retinopexy.
AB  - PURPOSE: To investigate the effect of injection technique parameters on the
      formation of multiple gas bubbles in a porcine eye model for pneumatic
      retinopexy. METHODS: Three hundred twenty-four adult porcine eyes were injected
      with 0.4 mL of C3F8 with variations in the depth of injection, speed of
      injection, and size of needle bore. The number of gas bubbles in the eye was
      assessed with indirect ophthalmoscopy. RESULTS: Shallow injections resulted in a
      higher incidence of a single bubble than did deep injections (P < 0.001; Fisher
      exact and Wilcoxon rank sum tests). Slow injections were significantly
      advantageous in producing a single gas bubble during shallow as well as during
      deep injections (P < 0.001, Fisher exact and Wilcoxon rank sum tests). With a
      shallow needle insertion, the slow speed of injection produced a single bubble in
      75.9% of the eyes, whereas moderately brisk injections resulted in one bubble in
      50.9% of the eyes. During deep needle insertion, 44.4% of the eyes had one bubble
      if the gas was injected slowly and only 11.1% had a single bubble with moderately
      brisk gas injections. The bore of the needle did not significantly change the
      number of bubbles during deep or shallow injections. CONCLUSIONS: The factors
      that were found to be important in reducing the formation of multiple gas bubbles
      in the eye were shallow depth of injection and slow speed of gas delivery.

PMID- 17525208
TI  - Glucose-6-phosphate dehydrogenase deficiency in retinal vein occlusion.
AB  - PURPOSE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most
      common human genetic abnormalities, with a high prevalence in Sardinia, Italy.
      Evidence indicates that G6PD-deficient patients are protected against ischemic
      heart and cerebrovascular disease. The purpose of this study was to assess the
      frequency of G6PD deficiency in Sardinian patients with retinal vein occlusion
      (RVO) and to ascertain whether the deficiency may offer protection against RVO.
      METHODS: Erythrocyte G6PD levels were measured in 448 consecutive RVO patients:
      194 with central RVO (CRVO) and 254 with branch RVO (BRVO). Age- and sex-matched
      subjects (n = 896) who were undergoing cataract surgery and had no history of RVO
      served as the control. Multiple logistic regression models were used to
      investigate the association between G6PD deficiency and RVO, CRVO, or BRVO.
      RESULTS: G6PD deficiency was found in 21 (4.7%) patients with RVO, 7 (3.6%) with
      CRVO, 14 (5.5%) with BRVO, and 107 (11.9%) control subjects. Differences between
      cases and controls were statistically significant (P < 0.005). Multiple
      conditional logistic regression analysis, including as covariates G6PD
      deficiency, hypertension, diabetes, and hypercholesterolemia, revealed that G6PD
      deficiency was significantly associated with decreased risk of development of
      RVO, CRVO, or BRVO. After adjustment for hypertension, diabetes, and
      hypercholesterolemia, the association between G6PD deficiency and RVO, CRVO, or
      BRVO remained statistically significant. Similar results were obtained after
      adjustment for systolic or diastolic blood pressure, plasma glucose, and
      cholesterol levels. However, when the patients with CRVO or BRVO were categorized
      by gender, a significant association was found only in the women. CONCLUSIONS:
      The frequency of G6PD deficiency in patients with RVO was significantly lower
      than expected. The results suggest that G6PD-deficient patients have a
      significantly decreased risk of development of RVO in the Sardinian population.

PMID- 17525207
TI  - Thrombin-induced VEGF expression in human retinal pigment epithelial cells.
AB  - PURPOSE: The purpose of the present study was to investigate the effects of
      thrombin and thrombin in combination with other proangiogenic factors on VEGF
      expression in hRPE cells. METHODS: hRPE cells were stimulated with thrombin TNF
      alpha, monocytes, and TGF-beta2. After stimulation, conditioned medium and lysed
      cells were subjected to ELISA, Western blot analysis, immunocytochemistry, and RT
      PCR analyses. Inhibitors specific for various signal transduction pathways were
      used to determine the signaling pathways involved. RESULTS: Treatment of RPE
      cells with thrombin resulted in dose- and time-dependent increases in VEGF mRNA
      levels and protein production. hRPE VEGF expression is predominantly protease
      activated receptor (PAR)-1 dependent. Approximately 80% of thrombin-induced VEGF
      secretion was abrogated by inhibitors of MAPK/ERK kinase (MEK), p38, c-Jun NH2
      terminal kinase (JNK), protein tyrosine kinase (PTK), phosphatidylinositol 3
      kinase (PI3K), protein kinase C (PKC), nuclear factor-kappaB (NF-kappaB), and
      reactive oxygen species (ROS). Analyses of VEGF protein production and mRNA
      synthesis revealed that VEGF induction by thrombin plus TNF-alpha or coculture
      with monocytes was additive, whereas that by co-incubation with TGF-beta2 was
      synergistic. The costimulated VEGF production by TGF-beta2 plus thrombin was an
      average of three times higher than the sum of that induced by each agent alone.
      Furthermore, BAPTA [bis-(o-aminophenoxy)ethane-N,N',N'-tetraacetic acid], a
      calcium chelator, blocked the VEGF secretion induced by thrombin and thrombin
      plus TGF-beta2 by 65% and 20%, respectively, but had no effect on that induced by
      TGF-beta2 alone. CONCLUSIONS: Thrombin alone and in combination with TNF-alpha,
      monocytes, and TGF-beta2 potently stimulated VEGF expression in hRPE cells via
      multiple signaling pathways. The thrombin-induced calcium mobilization may play
      an important permissive role in maximizing TGF-beta2-induced VEGF expression in
      RPE cells.

PMID- 17525209
TI  - Caspase-dependent apoptosis in light-induced retinal degeneration.
AB  - PURPOSE: To study the apoptotic mechanism involved in our model of light-induced
      retinal degeneration. METHODS: Rats were injected intravitreally with PBS, 2%
      dimethyl sulfoxide (DMSO), caspase inhibitor Z-VAD-FMK (1.06 mM), Z-YVAD-FMK
      (0.16 mM), or Z-DEVD-FMK (2 mM) before they were placed in constant light (3400
      lux) for 24 hours. Additional controls included rats that were uninjected or were
      punctured with a dry needle. Electroretinograms were recorded before injection
      and 1 day after the cessation of exposure to constant light. A group of rats was
      killed for apoptotic cell detection in the outer nuclear layer. Fifteen days
      later, the remaining rats were killed for histology, and the outer nuclear layer
      (ONL) thickness was measured. Caspase-1, caspase-3, and calpain activities were
      measured before and 1 day after exposure to the damaging light. RESULTS: ZVAD,
      YVAD, and DEVD inhibited caspase-1 and -3 activities, but not calpain activity,
      from the beginning and up to 1 day after light exposure. In untreated, dry needle
      punctured, PBS, DMSO, and YVAD groups, light exposure significantly reduced
      retinal function and ONL thickness and increased by 51-fold the number of
      apoptotic cells. ZVAD and DEVD preserved retinal function to 86% and 78%,
      respectively, and reduced by three times the number of apoptotic photoreceptors.
      ONL thickness was more preserved in ZVAD (to 72%) than in DEVD (to 56%).
      CONCLUSIONS: In the authors' model of retinal degeneration, photoreceptor cells
      die through a caspase-dependent mechanism. However, the molecular events involved
      during and after light exposure seemed to implicate different proteases.

PMID- 17525210
TI  - Attenuated glial reactions and photoreceptor degeneration after retinal
      detachment in mice deficient in glial fibrillary acidic protein and vimentin.
AB  - PURPOSE: To characterize the reactions of retinal glial cells (astrocytes and
      Muller cells) to retinal injury in mice that lack glial fibrillary acidic protein
      (GFAP) and vimentin (GFAP-/-Vim-/-) and to determine the role of glial cells in
      retinal detachment (RD)-induced photoreceptor degeneration. METHODS: RD was
      induced by subretinal injection of sodium hyaluronate in adult wild-type (WT) and
      GFAP-/-Vim-/- mice. Astroglial reaction and subsequent monocyte recruitment were
      quantified by measuring extracellular signal-regulated kinase (Erk) and c-fos
      activation and the level of expression of chemokine monocyte chemoattractant
      protein (MCP)-1 and by counting monocytes/microglia in the detached retinas.
      Immunohistochemistry, immunoblotting, real-time quantitative polymerase chain
      reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used. RD
      induced photoreceptor degeneration was assessed by terminal deoxynucleotidyl
      transferase dUTP nick-end labeling (TUNEL) and measurement of outer nuclear layer
      (ONL) thickness. RESULTS: RD-induced reactive gliosis, characterized by GFAP and
      vimentin upregulation, Erk and c-fos activation, MCP-1 induction, and increased
      monocyte recruitment in WT mice. Absence of GFAP and vimentin effectively
      attenuated reactive responses of retinal glial cells and monocyte infiltration.
      As a result, detached retinas of GFAP-/-Vim-/- mice exhibited significantly
      reduced numbers of TUNEL-positive photoreceptor cells and increased ONL thickness
      compared with those of WT mice. CONCLUSIONS: The absence of GFAP and vimentin
      attenuates RD-induced reactive gliosis and, subsequently, limits photoreceptor
      degeneration. Results of this study indicate that reactive retinal glial cells
      contribute critically to retinal damage induced by RD and provide a new avenue
      for limiting photoreceptor degeneration associated with RD and other retinal
      diseases or damage.

PMID- 17525211
TI  - Panretinal, high-resolution color photography of the mouse fundus.
AB  - PURPOSE: To analyze high-resolution color photographs of the mouse fundus.
      METHODS: A contact fundus camera based on topical endoscopy fundus imaging (TEFI)
      was built. Fundus photographs of C57 and Balb/c mice obtained by TEFI were
      qualitatively analyzed. RESULTS: High-resolution digital imaging of the fundus,
      including the ciliary body, was routinely obtained. The reflectance and contrast
      of retinal vessels varied significantly with the amount of incident and reflected
      light and, thus, with the degree of fundus pigmentation. The combination of
      chromatic and spherical aberration favored blue light imaging, in term of both
      field and contrast. CONCLUSIONS: TEFI is a small, low-cost system that allows
      high-resolution color fundus imaging and fluorescein angiography in conscious
      mice. Panretinal imaging is facilitated by the presence of the large rounded
      lens. TEFI significantly improves the quality of in vivo photography of retina
      and ciliary process of mice. Resolution is, however, affected by chromatic
      aberration, and should be improved by monochromatic imaging.

PMID- 17525212
TI  - Neurokinin-1 receptors located in human retinoblastoma cell lines: antitumor
      action of its antagonist, L-732,138.
AB  - PURPOSE: The authors have recently demonstrated that substance P and L-733,060
      induce cell proliferation and cell inhibition, respectively, in human
      retinoblastoma cell lines. However, the presence of neurokinin-1 receptors has
      not been demonstrated in such cell lines, nor is it known whether other
      neurokinin-1 receptor antagonists exert antitumoral action against retinoblastoma
      cell lines. The purpose of this study was to demonstrate the presence of
      neurokinin-1 receptors in the human retinoblastoma cell lines WERI-Rb-1 and Y-79
      and to study the growth inhibitory capacity of the neurokinin-1 receptor
      antagonist L-732,138 against those cell lines. The authors also sought to
      demonstrate that the administration of L-732,138 or L-733,060 induces apoptosis
      in retinoblastoma cells and that neurokinin-1 receptors and substance P are
      present in primary retinoblastoma. METHODS: Immunoblot analysis was used to
      determine neurokinin-1 receptors, and a Coulter counter was used to determine
      viable cell numbers; this was followed by application of the tetrazolium compound
      WST-8, a colorimetric method, to evaluate cell viability. DAPI stain was applied
      to assess chromatin condensation, characteristic of apoptosis, and
      immunoperoxidase was used to demonstrate neurokinin-1 receptors and substance P
      in eyes with primary retinoblastoma. RESULTS: Neurokinin-1 receptors were present
      in both retinoblastoma cell lines studied. Three identical bands (isoforms of
      approximately 33, 58, and 75 kDa) were observed in both cell lines. Moreover, L
      732,138 inhibited the growth of both cell lines studied, with and without
      previous administration of substance P. This inhibition occurred in a dose
      dependent manner, with the IC50 values of 60.47 microM for WERI-Rb1 and 56.78
      microM for Y-79. Moreover, apoptosis was observed in both cell lines after the
      administration of L-732,138 or L-733,060. In fixed eyes with primary
      retinoblastoma, a high density of neurokinin-1 receptors was observed in tumor
      cells, whereas a very low number of such cells contained substance P.
      CONCLUSIONS: This study showed that the same isoforms of the neurokinin-1
      receptor are present in human retinoblastoma cell lines WERI-Rb-1 and Y-79. Both
      L-732,138 and L-733,060 can induce apoptosis in these cell lines and therefore
      can act as antitumoral agents. Primary retinoblastoma specimens display
      neurokinin-1 receptor immunolabeling. These results suggest that the neurokinin-1
      receptor may be a promising new target for the treatment of retinoblastoma.

PMID- 17525213
TI  - Dendritic and synaptic plasticity of neurons in the human age-related macular
      degeneration retina.
AB  - PURPOSE: To determine whether structural plasticity is evident in human retinal
      tissues in response to age-related macular degeneration (AMD). Remodeling events
      such as sprouting of neuronal processes and the reconnection of synapses are
      essential elements in repairing any damage to adult nervous tissues such as might
      occur in response to insults such as strokes or in AMD. METHODS: The anatomic
      architecture of normal and AMD-affected human retinas was examined in the
      central, midperipheral, and far-peripheral regions. The retina, by virtue of its
      well-organized laminar structure, allows the identification and analysis of
      abnormal projections or connections of neuronal elements. RESULTS: In AMD
      afflicted retinas, but not in normal aged human retinas, a large number of
      photoreceptor synapses across the entire retina retract into the outer nuclear
      layer. This event evokes the subsequent outgrowth of dendrites from the
      postsynaptic bipolar cells, again across the entire retina, and the subsequent
      reformation of synaptic contacts between photoreceptor and bipolar cells.
      CONCLUSIONS: These findings illustrate that there are anatomic changes in the AMD
      retina at all eccentricities, not just in the macular region. Aged human retinal
      neurons have the capacity to form new synapses, and this finding may be important
      when investigating possible means of repairing the damaged human retina.

PMID- 17525214
TI  - Cytotoxicity of triamcinolone acetonide on human retinal pigment epithelial
      cells.
AB  - PURPOSE: To investigate the toxic effects of triamcinolone acetonide (TA)
      suspensions on human retinal pigment epithelial (RPE) cells. METHODS: Cultured
      human RPE cells were exposed for up to 2 hours to one of seven solutions: control
      (balanced salt solution, BSS; Alcon Laboratories, Ft. Worth TX), commercial TA
      suspension (cTA), cTA from which the vehicle (which contains the preservative
      benzyl alcohol) had been removed (vehicle-removed TA, -vTA), vehicle of the cTA
      (V), or a 1:10 dilution (in BSS; Alcon) of cTA, -vTA or V. Solution effects were
      evaluated by phase-contrast microscopy of cells stained in situ with trypan blue
      and in vitro by trypan blue exclusion assay. RPE cell function was assessed by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The
      mechanism of TA toxicity was studied by acridine orange-ethidium bromide staining
      and epifluorescence microscopy, and ultrastructural changes were examined by
      transmission electron microscopy (TEM). RESULTS: The effects of vehicle-removed
      solutions (-vTA and 1:10 -vTA) were similar to those of the control solution.
      Exposure for 1 hour or longer to a vehicle-containing solution (cTA and V)
      resulted in similar and significant degrees of cell damage that were dose and
      time dependent. The major mechanism of cell death was necrosis, and the early
      ultrastructural change was swelling of organelles in the cytoplasm. CONCLUSIONS:
      Preserved commercial TA suspensions damaged human RPE cells, but vehicle-free
      solutions did not. The authors suggest removing the vehicle as completely as
      possible from TA solutions before they are administered intravitreally.
      Furthermore, they recommend that a commercial formulation of preservative-free TA
      suspension be made available for intraocular use.

PMID- 17525215
TI  - Genetic ablation of cone photoreceptors eliminates retinal folds in the retinal
      degeneration 7 (rd7) mouse.
AB  - PURPOSE: Folds or pseudorosettes in the outer retina are commonly observed in
      animals with genetic, viral, or chemically induced retinal degeneration. This
      study examined the effect of genetic ablation of cone photoreceptors on the
      production of retinal folds in two mouse retinopathy models. One is the rd7/rd7
      retina, a model of enhanced S-cone syndrome, Goldman-Favre syndrome, and clumped
      pigmentary retinopathy that is also associated with an approximately twofold
      excess of S-cones. The other is postnatal day (P)0 N-methyl-N-nitrosourea (MNU)
      treatment. METHODS: A transgene that directs cone-specific expression of the
      diphtheria toxin A chain was used to ablate cone photoreceptors. Retinal folds,
      numbers of photoreceptors, and numbers of cones were quantified in retina
      flatmounts or transverse sections, and photoreceptor apoptosis was quantified by
      immunostaining for activated caspase 3. RESULTS: Cone ablation by the cone-DTA
      transgene eliminated folds in the rd7/rd7 retina, whereas chemical ablation of up
      to 30% of rods (by exposure to MNU at P13) had little or no effect on folds in
      the rd7/rd7 retina. Cone ablation by the cone-DTA transgene had no effect on
      retinal folds produced by P0 MNU treatment or on the progressive loss of rod
      photoreceptors in the rd7/rd7 retina. CONCLUSIONS: Despite their relatively low
      abundance, cones play a critical role in retinal folding in the rd7/rd7 retina.
      The relevant molecular and cellular mechanisms remain to be determined.

PMID- 17525216
TI  - Evaluating retinal function in age-related maculopathy with the ERG photostress
      test.
AB  - PURPOSE: To evaluate the diagnostic potential of the electroretinogram (ERG)
      photostress test and the focal cone ERG in age-related maculopathy (ARM).
      METHODS: The cohort comprised 31 patients with ARM and 27 age-matched control
      subjects. The ERG photostress test was used to monitor cone adaptation after
      intense light adaptation. Focal 41- and 5-Hz cone ERGs were recorded monocularly
      (central 20 degrees) to assess steady state retinal function. Univariate analysis
      identified electrophysiological parameters that differed between groups, and
      receiver operating characteristic (ROC) curves were constructed to assess their
      diagnostic potential. Logistic regression analysis determined the diagnostic
      potential of a model incorporating several independent predictors of ARM.
      RESULTS: The rate of recovery of the ERG photostress test was reduced (recovery
      was slower) in subjects with ARM. The parameter exhibited good diagnostic
      potential (P = 0.002, area under ROC curve = 0.74). The implicit times of the 5
      Hz (a-wave, P = 0.002; b-wave, P < 0.001) and the 41-Hz (P < 0.001) focal cone
      ERGs were increased, and the 41-Hz focal cone ERG amplitude (P = 0.003) and focal
      to full-field amplitude ratio (P = 0.001) were reduced in the ARM group. Logistic
      regression analysis identified three independent predictors of ARM, including the
      rate of recovery of the ERG photostress test. CONCLUSIONS: Early ARM has a marked
      effect on the kinetics of cone adaptation. The clinical application of the ERG
      photostress test increases the sensitivity and specificity of a model for the
      diagnosis of ARM. Improved assessment of the functional integrity of the central
      retina will facilitate early diagnosis and evaluation of therapeutic
      interventions.

PMID- 17525217
TI  - Penetration of bevacizumab through the retina after intravitreal injection in the
      monkey.
AB  - PURPOSE: The penetration of intravitreally injected bevacizumab in its commercial
      formulation (Avastin; Roche, Grenzach, Germany) through the retina was studied,
      to determine whether a full-length antibody would be able to penetrate the retina
      as easily as an antibody fragment. METHODS: Six cynomolgus monkeys (Macaca
      fascicularis) were used in this study. Two compositions of intravitreal injection
      into the right eyes were performed: one with commercial Avastin (group 1, four
      animals) and the other one with commercial Avastin labeled with 125I (group 2,
      one animal). The animals in group 1 were killed 1, 4, 7, or 14 days after the
      injection for subsequent histologic analysis of the eyes by immunohistochemistry,
      and the animal in group 2 was killed 7 days after injection for autoradiography
      and electron microscopy. Funduscopy was performed before the injection and at
      several time points thereafter. Moreover, blood samples were collected at
      different time points from the group-2 animal. The sixth animal remained
      untreated and served as the control. RESULTS: No pathologic changes were obvious
      in the funduscopic images within the time of the experiment. Bevacizumab
      immunoreactivity was found in the choroid and the inner layers of the retina as
      early as 1 day after the injection and spread to the outer layers and the choroid
      within the following days, in particular to photoreceptors and blood vessels.
      Avastin labeled with 125I showed radioactivity in blood serum 1 day after the
      intravitreal injection and remained relatively stable until day 7. CONCLUSIONS:
      The results clearly show that the bevacizumab molecule can penetrate the retina
      and is also transported into the retinal pigment epithelium, the choroid and, in
      particular, into photoreceptor outer segments after intravitreal injection of
      Avastin. Active transport mechanisms seem to be involved.

PMID- 17525218
TI  - Cellular reorganization in the human retina during normal aging.
AB  - PURPOSE: To characterize the nature and extent of neuronal reorganization in the
      human retina during normal aging. METHODS: Retinas of young (18-34 years old) and
      aged (68-77 years old) human donors were examined. Immunocytochemical methods and
      antibodies directed against Go-alpha, protein kinase C, parvalbumin, calbindin,
      calretinin, and choline acetyltransferase were used to stain different retinal
      cell types. Confocal images of retinal sections from the optic disc to the
      peripheral edge were taken at three eccentricities, and the density and length of
      cellular processes were quantified with neuroanatomical analysis software.
      RESULTS: Dendritic fibers of rod and On-cone bipolar cells were found to extend
      well beyond the normal boundary of the outer plexiform layer (OPL) into the outer
      nuclear layer (ONL) in aged retinas. Length and density of these elongated fibers
      were significantly greater in aged than in young retinas. This phenomenon
      demonstrated a clear spatial gradient that was most prevalent in the periphery
      and was infrequent in the central region of the retina. Horizontal cells, which
      normally make triad synaptic connections with photoreceptors and bipolar cells,
      also had dendrites that extended into the ONL in aged retinas, and these were
      spatially juxtaposed with the elongated dendrites of bipolar cells. CONCLUSIONS:
      Rod and On-cone bipolar cells, as well as horizontal cells of the human retina,
      undergo extensive dendritic reorganization during normal aging. Although
      literature on aging has tended to emphasize degenerative and regressive changes,
      the present findings provide evidence for a remarkable degree of cellular
      plasticity in the aged human retina.

PMID- 17525219
TI  - Effects of periocular administration of triamcinolone acetonide on leukocyte
      endothelium interactions in the ischemic retina.
AB  - PURPOSE: Recent studies have reported that intravitreal or posterior sub-Tenon's
      injection of triamcinolone acetonide (TA) is effective in the treatment of
      macular edema resulting from retinal microcirculatory disturbances such as
      diabetic retinopathy and retinal vein occlusion. The effects of periocular
      administration of TA on leukocyte-endothelium interactions were studied after
      transient retinal ischemia. METHODS: Transient retinal ischemia was induced by
      temporary ligation of the optic nerve sheath for 60 minutes in male Long-Evans
      rats. After the induction of ischemia, experimental eyes received a periocular
      injection of TA (2 mg). In control animals, the same volume of saline was
      administered. Leukocyte dynamics were evaluated in the retinal microcirculation
      using acridine orange digital fluorography. Also, retinal thickness was studied
      by using optical coherence tomography and a histologic METHOD: The retinal mRNA
      expression of P-selectin and intercellular adhesion molecule (ICAM)-1 was
      semiquantitatively studied with RT-PCR. RESULTS: The leukocytes rolling along
      retinal vein linings increased after ischemia in the vehicle-treated rats (32.5
      +/- 2.1 cells/min). No rolling leukocytes, however, were seen in the TA-treated
      rats. The number of accumulated leukocytes was significantly lower in the TA
      treated rats (831 +/- 99 cells/mm2) than in the control (971 +/- 81 cells/mm2, P
      < 0.05). The treatment decreased the retinal thickness and the mRNA expression of
      P-selectin and ICAM-1. CONCLUSIONS: The present study demonstrated that the
      periocular injection of TA effectively decreased retinal thickness and inhibited
      leukocyte-endothelium interactions in the retina after ischemia. Downregulation
      of adhesion molecules of retinal vascular endothelium induced by TA may play a
      role in the course.

PMID- 17525220
TI  - Interaction between the photoreceptor-specific tubby-like protein 1 and the
      neuronal-specific GTPase dynamin-1.
AB  - PURPOSE: Tubby-like proteins (TULPs) are a family of four proteins, two of which
      have been linked to neurosensory disease phenotypes. TULP1 is a photoreceptor
      specific protein that is mutated in retinitis pigmentosa, an inherited retinal
      disease characterized by the degeneration of rod and cone photoreceptor cells. To
      investigate the function of TULP1 in maintaining the health of photoreceptors,
      the authors sought the identification of interacting proteins. METHODS:
      Immunoprecipitation from retinal lysates, followed by liquid chromatography
      tandem mass spectrometry and in vitro binding assays, were used to identify TULP1
      binding partners. RT-PCR was performed on total RNA from wild-type mouse retina
      to identify the Dynamin-1 isoform expressed in the retina. Immunocytochemistry
      was used to determine the localization of TULP1 and Dynamin-1 in photoreceptor
      cells. Electroretinography (ERG) and light microscopy were used to phenotype
      tulp1-/- mice at a young age. RESULTS: Immunoprecipitation from retinal lysate
      identified Dynamin-1 as a possible TULP1 binding partner. GST pull-down assays
      further supported an interaction between TULP1 and Dynamin-1. In photoreceptor
      cells, Dynamin-1 and TULP1 colocalized primarily to the outer plexiform layer,
      where photoreceptor terminals synapse on second-order neurons and, to a lesser
      extent, to the inner segments, where polarized protein translocation occurs. ERG
      analyses in young tulp1-/- mice indicated a decreased b-wave at ages when the
      retina retained a full complement of photoreceptor cells. CONCLUSIONS: These data
      indicated that TULP1 interacts with Dynamin-1 and suggested that TULP1 is
      involved in the vesicular trafficking of photoreceptor proteins, both at the
      nerve terminal during synaptic transmission and at the inner segment during
      protein translocation to the outer segment. These results also raised the
      possibility that normal synaptic function requires TULP1, and they motivate a
      closer look at synaptic architecture in the developing tulp1-/- retina.

PMID- 17525221
TI  - Histone deacetylase inhibition-mediated differentiation of RGC-5 cells and
      interaction with survival.
AB  - PURPOSE: The acetylation state of histones is modulated by histone deacetylase
      (HDAC) and histone acetyltransferase and is an important component in regulating
      gene transcription, including neuronal differentiation. The authors studied the
      relationship between histone acetylation and the differentiation and survival of
      the RGC-5 cell line and compared it with nontranscriptional-dependent
      differentiation with staurosporine. METHODS: The retinal ganglion cell line RGC-5
      was treated with trichostatin A (TSA), other HDAC inhibitors, and staurosporine;
      differentiation, neuritogenesis, neurotrophic factor dependence, and dependence
      on RNA transcription were assessed. RESULTS: TSA caused significant
      differentiation and neuritogenesis. Differences between HDAC inhibition and
      staurosporine differentiation included the proportion of differentiated cells,
      cell viability, cell morphology, and transcriptional dependence. HDAC inhibition,
      but not staurosporine differentiation, resulted in RGC-5 cells that were
      neurotrophic factor dependent. CONCLUSIONS: These results implicate two different
      mechanisms for RGC-5 differentiation, with a common downstream effect on neurite
      outgrowth but a differential effect on neurotrophic factor dependence.

PMID- 17525222
TI  - All-trans-retinol generated by rhodopsin photobleaching induces rapid recruitment
      of TIP47 to lipid droplets in the retinal pigment epithelium.
AB  - PURPOSE: To investigate the effect of light stimulation on lipid droplets (LDs)
      and LD proteins in the retinal pigment epithelium (RPE). METHODS: Dark-adapted
      mouse eyes were exposed to intense flashes of light, and ARPE-19 cells were
      treated with all-trans-retinol. The two specimens were labeled with BODIPY493/503
      for LDs and with antibodies for three LD proteins: adipocyte differentiation
      related protein (ADRP), TIP47, and Rab18. The labeling intensity in fluorescence
      microscopy was quantified by image analysis. Localization of mutated TIP47 was
      also examined. Immunoelectron microscopy was performed for ADRP in mouse RPE.
      Expression of TIP47 in ARPE-19 cells was knocked down by RNA interference (RNAi),
      and its effect on retinyl ester storage was measured by HPLC. RESULTS: Both
      flashes of light on mouse eyes and all-trans-retinol on ARPE-19 cells caused
      rapid translocation of TIP47 from the cytosol to LDs, whereas ADRP distributed
      constitutively in LDs. The density of LDs did not show visible changes by any
      treatment. The localization of TIP47 to LDs was abolished when either the amino
      terminal or the carboxyl-terminal half of the molecule was deleted, but was
      enhanced by a short deletion in the carboxyl terminus. Manipulation of TIP47
      expression by RNAi or cDNA transfection did not affect the retinyl ester amounts
      in ARPE-19 cells significantly. CONCLUSIONS: All-trans-retinol generated by
      photobleaching in the retina induces rapid translocation of TIP47 to LDs in the
      RPE.

PMID- 17525223
TI  - Transport of truncated rhodopsin and its effects on rod function and
      degeneration.
AB  - PURPOSE: Most transgenic animal models of retinal degeneration caused by
      rhodopsin mutations express the rhodopsin transgene on a wild-type (WT) genetic
      background. Previous studies have demonstrated that one mechanism of retinal
      degeneration is rhodopsin overexpression. To study the effect of C-terminal
      truncation of rhodopsin without the confounding factors of overexpression,
      several lines of transgenic mice were generated that expressed a C-terminal
      rhodopsin mutation on rhodopsin-knockout backgrounds. METHODS: Two lines of
      transgenic mice, expressing different levels of C-terminal truncated rhodopsin
      (S334ter) were mated with heterozygous rhodopsin-knockout (rho+/-) mice to
      express S334ter rhodopsin on a background with reduced endogenous rhodopsin
      expression. S334ter mice were mated to homozygous knockout (rho-/-) mice to
      examine the effect of S334ter rhodopsin on a null rhodopsin background. S334ter
      rhodopsin expression was estimated by Western blot. Retinal function was assessed
      by ERG and retinal degeneration by histopathology and morphometry. C-terminal
      rhodopsin sorting and trafficking was examined by fluorescence
      immunocytochemistry with detection by electron microscope. RESULTS: Expression of
      S334ter truncated rhodopsin at low levels in the presence of decreased total
      rhodopsin in rods (S334ter, rho+/-) increased the rate of rod cell death in
      comparison to rho+/- littermates. In addition, S334ter rhodopsin prolonged the
      recovery time of the rod ERG to a light flash and diminished the a-wave
      amplitudes in comparison to their (rho+/-) littermates. Photoreceptors of S334ter
      mice on a homozygous rhodopsin-knockout background (S334ter+, rho-/-) had a
      fraction of mutant rhodopsin localized to the ciliary membranes. CONCLUSIONS:
      Expression of S334ter rhodopsin without overexpression of total opsin in the rod
      photoreceptor decreased rod cell contribution to the ERG and compromised rod cell
      survival in adult mice. The increased cell death may be a consequence of C
      terminal truncated rhodopsin mislocalization in membranes of the inner segment.
      Another possible pathologic mechanism is prolonged activation of
      phototransduction from the presence of mutant rhodopsin in the outer segment
      lacking the normal C-terminal binding sites for shutoff by arrestin and
      phosphorylation. These results suggest that rhodopsin lacking a C-terminal
      trafficking signal can be transported to the rod outer segment without
      cotransporting with full-length rhodopsin.

PMID- 17525224
TI  - Paradoxical role of BDNF: BDNF+/- retinas are protected against light damage
      mediated stress.
AB  - PURPOSE: Photoreceptors can be prevented from undergoing apoptosis in response to
      constant light by the application of exogenous neuroprotective agents, including
      brain-derived neurotrophic factor (BDNF). BDNF, however, cannot exert its effect
      directly on photoreceptors because they do not express receptors for BDNF. It has
      been proposed that BDNF released from Muller cells provides a feed-forward loop,
      increasing ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor
      (bFGF) production in Muller cells, which may enhance photoreceptor survival. The
      authors hypothesized that retinas with reduced BDNF levels in which the BDNF
      mediated release of neuroprotective signals is dampened are more susceptible to
      light-induced photoreceptor degeneration. METHODS: Young adult BDNF+/+ and BDNF+/
      littermates (B6.129-BDNF(tm1-LT)) were analyzed. Retinal neurotrophin and growth
      factor mRNA levels were determined by quantitative RT-PCR, photoreceptor function
      was assessed through electroretinography, and survival was documented in
      morphologic sections and in TUNEL assays. Oxidative stress was assayed by
      measuring glutathione peroxidase activity. RESULTS: At baseline, BDNF+/- animals
      had significantly increased levels of glial-derived neurotrophic factor (GDNF)
      mRNA compared with their wild-type littermates. After light damage GDNF, CNTF,
      and BDNF mRNA levels dropped 14- to 16-fold in the BDNF+/+ mice but remained
      almost unchanged compared with baseline levels in the BDNF+/- mice. Preservation
      of neurotrophin levels in BDNF+/- mice correlated with photoreceptor cell
      survival, preservation of function, and reduced oxidative stress. CONCLUSIONS:
      Contrary to the hypothesis, reducing BDNF levels resulted in photoreceptor
      protection against light damage. Survival was paralleled by a reduction in
      oxidative stress and the preservation of neurotrophin levels, suggesting that
      chronic reduction of BDNF in the retina provides a level of preconditioning
      against stress.

PMID- 17525225
TI  - Impaired retinal differentiation and maintenance in zebrafish laminin mutants.
AB  - PURPOSE: To characterize morphologic and physiological alterations in the retina
      of three laminin mutant zebrafish, bashful (bal, lama1), grumpy (gup, lamb1), and
      sleepy (sly, lamc1), which were identified in forward genetic screens and were
      found to be impaired in visual functions. METHODS: Mutant larvae were observed
      for defects in visual behavior by testing their optokinetic response (OKR). In
      addition, electroretinograms (ERG) were measured and retinal morphology was
      examined by standard histology, immunocytochemistry, TUNEL assay, and electron
      microscopy. RESULTS: Both, gup and sly showed no OKR at any light intensity
      tested, whereas bal embryos showed some remaining OKR behavior at more than 40%
      of contrast. Consistent with the OKR result, gup and sly did not show an ERG
      response at any light intensity tested, whereas bal mutants exhibited small a-
      and b-waves at high light intensities. All three laminin mutants showed altered
      ganglion cell layers, optic nerve fasciculations, and lens defects. Again, bal
      showed the least severe morphologic phenotype with no additional defects. In
      contrast, both, gup and sly, showed severe photoreceptor outer segment shortening
      and synapse alteration (floating ribbons) as well as increased cell death.
      CONCLUSIONS: Lamb1 and lamc1 chains play an important role in the morphogenesis
      of photoreceptors and their synapses. In contrast, lama1 is not involved in outer
      retina development.

PMID- 17525226
TI  - Screening and diagnosis of optic pathway gliomas in children with
      neurofibromatosis type 1 by using sweep visual evoked potentials.
AB  - PURPOSE: Neurofibromatosis type 1 (NF-1) is an autosomal dominant phakomatosis
      with a prevalence of 1 in 2000 to 1 in 5000. Up to 24% of these patients have
      optic pathway gliomas (OPGs). In the present study, the use of sweep visual
      evoked potentials (SVEPs) was investigated as a screening tool for identifying
      patients with NF-1 who had OPGs by comparing them to those patients with no OPGs
      and to normally developing children. METHODS: Contrast sensitivity and grating
      acuity were measured with the SVEP. Sixteen children with OPGs (OPG group), 14
      children with NF-1 without OPGs (nOPG), and 16 aged-matched control subjects were
      recruited. All participants had best-corrected visual acuity of 6/9 or better.
      All were tested monocularly. RESULTS: Comparisons between groups by using the
      Tukey B test showed a significant reduction of mean log contrast sensitivity in
      the OPG group (1.55) compared with the nOPG (1.9, P = 0.006) and control (2.10, P
      < 0.001) group. There was no significant difference between the nOPG and control
      groups (P = 0.195). Grating acuity was comparable between groups, and no
      statistically significant differences were found. Log contrast sensitivity was
      moderately sensitive in identifying patients with OPG and was highly specific in
      screening out patients with no OPG. CONCLUSIONS: Children with OPGs have reduced
      contrast sensitivity when assessed using the SVEP. Children with no OPGs display
      no differences in visual functioning compared with control subjects. The findings
      suggest that the SVEP can be a useful and noninvasive screening tool for early
      detection of visual pathway gliomas in children with NF-1 and normal visual
      acuity.

PMID- 17525227
TI  - Intrinsic signal imaging in macaque retina reveals different types of flash
      induced light reflectance changes of different origins.
AB  - PURPOSE: Intrinsic signal imaging is a newly developed technique that can map the
      neural activity of tissues noninvasively. It has been used to map the functional
      organization of the retina by recording flash-induced light reflectance changes
      in the cone and rod photoreceptors. The purpose of this study was to investigate
      the properties of the intrinsic signals in the monkey's retina. To accomplish
      this, the intrinsic signals and the electroretinograms (ERGs) evoked by the same
      stimuli were measured under different recording conditions. METHODS: The fundus
      of macaque monkeys was observed with infrared light and recorded with a charge
      coupled device (CCD) camera. The intrinsic signals were measured as retinal light
      reflectance changes induced by diffuse or focal flash stimuli. ERGs were recorded
      under the same stimulating conditions. The reflectance changes induced by
      different flash intensities, flash intervals, and background luminance were
      compared. RESULTS: The intrinsic signals were categorized into different groups
      based on the location in the fundus. Fast signals (peak: approximately 100 ms)
      were recorded from the posterior retina including the fovea, and slow signals
      (peak: 5.0-6.0 seconds) were recorded from the optic disc and nonfoveal posterior
      retina. The threshold of the slow signal changes was comparable to that of the
      ERG b-wave, and the thresholds of the fast signals were higher than that of the
      ERG a- and b-waves. CONCLUSIONS: The retinal intrinsic signals are composed of
      several components with different response properties and different sources. This
      recording technique may be useful for mapping the retinal function in eyes with
      various disorders.

PMID- 17525228
TI  - Sources of motion-sensitivity loss in glaucoma.
AB  - PURPOSE: Primary open angle glaucoma (POAG) is a leading cause of irreversible
      adult blindness and is characterized by progressive optic neuropathy and
      constriction of the visual field. Behavioral tests for POAG target retinal
      ganglion cell (RGC) classes that have reduced redundancy or that might be
      selectively damaged, but these tests cannot differentiate dysfunctional from
      nonfunctional RGC inputs to motion sensors. In this study, a signal-to-noise
      motion-sensitivity task was used to investigate the sources of motion-sensitivity
      loss in patients with POAG. METHODS: An equivalent noise paradigm was used to
      investigate sensitivity to the direction of radial optic flow patterns across the
      visual field in visually normal observers and patients with POAG. Internal noise
      and sampling efficiency were estimated from the direction of heading contrast
      discrimination thresholds as a function of the level of added external noise.
      RESULTS: Contrast sensitivity to optic flow fell with retinal eccentricity for
      all observers, and decreased with both age and POAG. Equivalent noise analysis
      showed that the fall-off with eccentricity was primarily due to reduced sampling
      efficiency with relatively little increase in the level of internal noise and
      that the fall-off with age was attributable to both sources of error. Compared
      with age-matched control observers, patients with POAG have similar levels of
      internal noise but significantly lower sampling efficiency at all retinal loci.
      CONCLUSIONS: Motion-sensitivity losses with age, eccentricity, and POAG can arise
      from higher levels of internal noise and lower sampling efficiency. The central
      and peripheral glaucomatous neuropathy is mostly attributable to a reduction in
      sampling efficiency, suggesting that RGCs are nonfunctional rather than
      dysfunctional in this condition.

PMID- 17525229
TI  - Macular pigment: a test of the acuity hypothesis.
AB  - PURPOSE: Schultze, in 1866, originally proposed that macular pigment (MP) could
      improve acuity by reducing the deleterious effects associated with the aberration
      of short-wave (SW) light. Although proposed well more than a century ago, the
      hypothesis has never been empirically tested. The authors chose to begin
      evaluating the acuity hypothesis by measuring MP levels, gap, and hyperacuity in
      the same observers. METHODS: Eighty healthy young subjects were assessed. Forty
      subjects were assigned to the gap acuity experiment and 40 to the hyperacuity
      experiment. Peak MP optical density (MPOD) was measured using heterochromatic
      flicker photometry (HFP). Resolution and hyperacuity were measured as the minimum
      perceivable gap between two solid black lines (1'' width) vertically separated
      and as a vernier offset, respectively. These targets were presented on a 0.5
      degrees circular diffusing background that appeared either white (17 cd/m2) or
      yellow (16 cd/m2). The yellow background was produced by using light-emitting
      diodes (LEDs) with a peak lambda = 570 nm. The white background was produced by
      combining the yellow with a blue LED (peak lambda = 460 nm). The subject's head
      (5.33 m from the stimulus) was stabilized with a head-rest assembly, and the
      adaptive state was controlled with the use of a constant white surround (11
      cd/m2). Thresholds were determined based on probit analysis of psychometric
      functions generated using a two-alternative forced-choice procedure. RESULTS:
      MPOD ranged from 0.14 to 1.00 measured at 30' eccentricity. Gap and hyperacuity
      measures each varied by a factor of approximately 5 to 6. Average gap acuity (N =
      38) for the white condition (filtered by MP) was 31.2'' (SD = 9.4) and did not
      differ from the average (N = 38) for the yellow condition (not filtered by MP),
      which was 32.1'' (SD = 10.9). Similarly, average hyperacuity for the white
      condition (7.0''; SD = 2.9) did not differ from that of the yellow condition
      (6.8''; SD = 3.5). CONCLUSIONS: MPOD did not correlate significantly with gap or
      hyperacuity measured in the yellow or white conditions. These data, therefore, do
      not support the predictions of the acuity hypothesis.

PMID- 17525230
TI  - Effect of blur adaptation on blur sensitivity and discrimination in emmetropes
      and myopes.
AB  - PURPOSE: To determine whether blur adaptation influences blur sensitivity and
      blur discrimination thresholds in young adult myopes and emmetropes. In addition,
      to determine whether there is a differential effect of blur adaptation on blur
      sensitivity and discrimination between refractive error groups. METHODS: Proximal
      and distal blur sensitivity thresholds and blur discrimination thresholds were
      measured under cycloplegia with a Badal optometer in 24 young adult subjects (8
      emmetropes [EMM], 8 early-onset myopes [EOM], and 8 late-onset myopes [LOM]).
      Adaptation to 1 D of myopic refractive blur was then undertaken for 30 minutes.
      Blur sensitivity and discrimination thresholds were then remeasured. RESULTS:
      After blur adaptation, blur sensitivity, and blur discrimination thresholds were
      found to be elevated. Blur adaptation had a significant effect on distal blur
      sensitivity threshold, with the largest effect being observed in the EOMs. Mean
      changes in distal blur sensitivity thresholds were EMMs +0.03 +/- 0.14 D, EOMs
      +0.30 +/- 0.21 D, and LOMs +0.08 +/- 0.13 D. CONCLUSIONS: Adaptation to a
      degraded stimulus modifies the blur detection mechanisms of the visual system in
      young adults. Depth of focus is expanded by prolonged exposure to defocus. EOMs
      are more susceptible to this phenomenon than are LOMs and EMMs.

PMID- 17525231
TI  - Visual spatial integration in the elderly.
AB  - PURPOSE: To investigate the effect of ageing on contour integration in subjects
      whose ages ranged from 20 to 99 years. METHODS: Detection thresholds were
      measured for a closed chain of Gabor patches oriented tangentially to a circle
      (target) embedded in a background of randomly positioned and oriented Gabors
      (noise). Detection thresholds were measured for different distances of elements
      composing the target. RESULTS: Sensitivity decreases gradually with age at all
      interelement distances. Sensitivity decreases with increasing interelement
      distance, in both young and elderly subjects. The decrease of integration
      capability with age is not related to a decrease in contrast sensitivity.
      CONCLUSIONS: Overall, the data provide evidence of a deterioration of cortical
      functionality with age, in agreement with other studies on texture and motion
      processing.

PMID- 17525232
TI  - Concise review: Dendritic cell development in the context of the spleen
      microenvironment.
AB  - The dendritic cell (DC) population in spleen comprises a mixture of cells
      including endogenous DC progenitors, DC precursors migrating in from blood and
      bone marrow, and DC in different states of differentiation and activation. A role
      for different microenvironments in supporting the dynamic development of murine
      DC of different types or lineages is considered here. Recent evidence for
      production of DC dependent on splenic stromal cells is reviewed in the light of
      evidence that cell production is dependent on cells comprising an endothelial
      niche in spleen. The possibility that self-renewing progenitors in spleen give
      rise to DC with tolerogenic or regulatory rather than immunostimulatory function
      is considered.

PMID- 17525233
TI  - High histone acetylation and decreased polycomb repressive complex 2 member
      levels regulate gene specific transcriptional changes during early embryonic stem
      cell differentiation induced by retinoic acid.
AB  - Histone modifications play a crucial role during embryonic stem (ES) cell
      differentiation. During differentiation, binding of polycomb repressive complex 2
      (PRC2), which mediates trimethylation of lysine 27 on histone H3 (K27me3), is
      lost on developmental genes that are transcriptionally induced. We observed a
      global decrease in K27me3 in as little as 3 days after differentiation of mouse
      ES cells induced by retinoic acid (RA) treatment. The global levels of the
      histone K27 methyltransferase EZH2 also decreased with RA treatment. A loss of
      EZH2 binding and K27me3 was observed locally on PRC2 target genes induced after 3
      days of RA, including Nestin. In contrast, direct RA-responsive genes that are
      rapidly induced, such as Hoxa1, showed a loss of EZH2 binding and K27me3 after
      only a few hours of RA treatment. Following differentiation induced by leukemia
      inhibitor factor (LIF) withdrawal without RA, Hoxa1 was not transcriptionally
      activated. Small interfering RNA-mediated knockdown of EZH2 resulted in loss of
      K27me3 during LIF withdrawal, but the Hoxa1 gene remained transcriptionally
      silent after loss of this repressive mark. Induction of histone hyperacetylation
      overrode the repressive K27me3 modification and resulted in Hoxa1 gene
      expression. Together, these data show that there are multiple temporal phases of
      derepression of PRC2 target genes during ES cell differentiation and that other
      epigenetic marks (specifically, increased acetylation of histones H3 and H4), in
      addition to derepression, are important for gene-specific transcriptional
      activation. This report demonstrates the temporal interplay of various epigenetic
      changes in regulating gene expression during early ES cell differentiation.

PMID- 17525234
TI  - Chemotaxis and differentiation of human adipose tissue CD34+/CD31- progenitor
      cells: role of stromal derived factor-1 released by adipose tissue capillary
      endothelial cells.
AB  - The native CD34+/CD31- cell population present in the stroma-vascular fraction of
      human adipose tissue (hAT) displays progenitor cell properties since they exhibit
      adipocyte- and endothelial cell-like phenotypes under appropriate stimuli. To
      analyze the signals within hAT regulating their phenotypes, the influence of hAT
      derived capillary endothelial cells (CECs) was studied on the chemotaxis and
      differentiation of the hAT-CD34+/CD31- cells. Conditioned medium from hAT-CECs
      led to a strong chemotaxis of the hAT-CD34+/CD31- cells that was inhibited with
      pretreatments with pertussis toxin, CXCR-4 antagonist, or neutralizing
      antibodies. Furthermore, hAT-CECs produced and secreted the CXCR-4 ligand, that
      is, the stromal derived factor-1 (SDF-1). Finally, hAT-CECs induced the
      differentiation of hAT-CD34+/CD31- cells toward an endothelial cell (EC)
      phenotype. Indeed, hAT-CECs and -CD34+/CD31- cell coculture stimulated in a two
      dimensional system the expression of the EC CD31 marker by the hAT-progenitor
      cells and, in a three-dimensional approach, the formation of capillary-like
      structures via a SDF-1/CXCR-4 dependent pathway. Thus, the migration and
      differentiation of hAT progenitor cells are modulated by hAT-CEC-derived factors.
      SDF-1, which is secreted by hAT-derived CECs, and its receptor CXCR-4, expressed
      by hAT-derived progenitor cells, may promote chemotaxis and differentiation of
      hAT-derived progenitor cells and thus contribute to the formation of the vascular
      network during the development of hAT.

PMID- 17525235
TI  - Enhanced unique pattern of hematopoietic cell mobilization induced by the CXCR4
      antagonist 4F-benzoyl-TN14003.
AB  - An increase in the number of stem cells in blood following mobilization is
      required to enhance engraftment after high-dose chemotherapy and improve
      transplantation outcome. Therefore, an approach that improves stem cell
      mobilization is essential. The interaction between CXCL12 and its receptor,
      CXCR4, is involved in the retention of stem cells in the bone marrow. Therefore,
      blocking CXCR4 may result in mobilization of hematopoietic progenitor and stem
      cells. We have found that the CXCR4 antagonist known as 4F-benzoyl-TN14003 (T
      140) can induce mobilization of hematopoietic stem cells and progenitors within a
      few hours post-treatment in a dose-dependent manner. Furthermore, although T-140
      can also increase the number of white blood cells (WBC) in blood, including
      monocytes, B cells, and T cells, it had no effect on mobilizing natural killer
      cells. T-140 was found to efficiently synergize with granulocyte colony
      stimulating factor (G-CSF) in its ability to mobilize WBC and progenitors, as
      well as to induce a 660-fold increase in the number of erythroblasts in
      peripheral blood. Comparison between the CXCR4 antagonists T-140 and AMD3100
      showed that T-140 with or without G-CSF was significantly more potent in its
      ability to mobilize hematopoietic stem cells and progenitors into blood. These
      results demonstrate that different CXCR4 antagonists may have different
      therapeutic potentials.

PMID- 17525236
TI  - A tissue engineering approach to progenitor cell delivery results in significant
      cell engraftment and improved myocardial remodeling.
AB  - Cell replacement therapy has become an attractive solution for myocardial repair.
      Typical cell delivery techniques, however, suffer from poor cell engraftment and
      inhomogeneous cell distributions. Therefore, we assessed the hypothesis that an
      epicardially applied, tissue-engineered cardiac patch containing progenitor cells
      would result in enhanced exogenous cell engraftment. Human mesenchymal stem cells
      (hMSCs) were embedded into a rat tail type I collagen matrix to form the cardiac
      patch. Myocardial infarction was induced by left anterior descending coronary
      artery ligation in immunocompetent male cesarean-derived fischer rats, and
      patches with or without cells were secured to hearts with fibrin sealant. After
      patch formation, hMSCs retained a viability of >90% over 5 days in culture. In
      addition, >75% of hMSCs maintained a high degree of potency prior to patch
      implantation. After 4 days in culture, patches were applied to the epicardial
      surface of the infarct area and resulted in 23% +/- 4% engraftment of hMSCs at 1
      week (n = 6). Patch application resulted in a reduction in left ventricle
      interior diameter at systole, increased anterior wall thickness, and a 30%
      increase in fractional shortening. Despite this improvement in myocardial
      remodeling, hMSCs were not detectable at 4 weeks after patch application,
      implying that improvement did not require long-term cell engraftment. Patches
      devoid of progenitor cells showed no improvement in remodeling. In conclusion,
      pluripotent hMSCs can be efficiently delivered to a site of myocardial injury
      using an epicardial cardiac patch, and such delivery results in improved
      myocardial remodeling after infarction. Disclosure of potential conflicts of
      interest is found at the end of this article.

PMID- 17525237
TI  - Isolation and characterization of neural crest progenitors from adult dorsal root
      ganglia.
AB  - After peripheral nerve injury, the number of sensory neurons in the adult dorsal
      root ganglia (DRG) is initially reduced but recovers to a normal level several
      months later. The mechanisms underlying the neuronal recovery after injury are
      not clear. Here, we showed that in the DRG explant culture, a subpopulation of
      cells that emigrated out from adult rat DRG expressed nestin and p75 neurotrophin
      receptor and formed clusters and spheres. They differentiated into neurons, glia,
      and smooth muscle cells in the presence or absence of serum and formed secondary
      and tertiary neurospheres in cloning assays. Molecular expression analysis
      demonstrated the characteristics of neural crest progenitors and their potential
      for neuronal differentiation by expressing a set of well-defined genes related to
      adult stem cells niches and neuronal fate decision. Under the influence of
      neurotrophic factors, some of these progenitors gave rise to neuropeptide
      expressing cells and protein zero-expressing Schwann cells. In a 5-bromo-2'
      deoxyuridine chasing study, we showed that these progenitors likely originate
      from satellite glial cells. Our study suggests that a subpopulation of glia in
      adult DRG is likely to be progenitors for neurons and glia and may play a role in
      neurogenesis after nerve injury. Disclosure of potential conflicts of interest is
      found at the end of this article.

PMID- 17525238
TI  - Functional expression of ion channels in mesenchymal stem cells derived from
      umbilical cord vein.
AB  - Mesenchymal stem cells have the ability to renew and differentiate into various
      lineages of mesenchymal tissues. We used undifferentiated human mesenchymal-like
      stem cells from human umbilical cord vein (hUC-MSCs), a cell line which contains
      several mesenchymal cell markers. We characterized functional ion channels in
      cultured hUC-MSCs with whole-cell patch clamp and reverse transcription
      polymerase chain reaction (RT-PCR). Three types of outward current were found in
      these cells: the Ca(2+)-activated K(+) channel (IK(Ca)), a transient outward K(+)
      current (I(to)), and a delayed rectifier K(+) current (IK(DR)). IK(Ca) and IK(DR)
      were totally suppressed by tetraethylammonium, and IK(Ca) was sensitive to a
      specific blocker, iberiotoxin. I(to) was inhibited by 4-aminopyridine. Another
      type of inward rectifier K(+) current (K(ir)) was also detected in approximately
      5% of hUC-MSCs. Elevation of external potassium ion concentration increased the
      K(ir) current amplitude and positively shifted its reversal potential. In
      addition, inward Na(+) current (I(Na)) was found in these cells ( approximately
      30%); the current was blocked by tetrodotoxin and verapamil. In the RT-PCR
      analysis, Kv1.1, Kv4.2, Kv1.4, Kir2.1, heag1, MaxiK, hNE-Na, and TWIK-1 were
      detected. These results suggested that multiple functional ion channel currents,
      IK(Ca), IK(DR), I(to), I(Na), and K(ir), are expressed in hUC-MSCs. Disclosure of
      potential conflicts of interest is found at the end of this article.

PMID- 17525239
TI  - MIO-M1 cells and similar muller glial cell lines derived from adult human retina
      exhibit neural stem cell characteristics.
AB  - Growing evidence suggests that glial cells may have a role as neural precursors
      in the adult central nervous system. Although it has been shown that Muller cells
      exhibit progenitor characteristics in the postnatal chick and rat retinae, their
      progenitor-like role in developed human retina is unknown. We first reported the
      Muller glial characteristics of the spontaneously immortalized human cell line
      MIO-M1, but recently we have derived similar cell lines from the neural retina of
      several adult eye donors. Since immortalization is one of the main properties of
      stem cells, we investigated whether these cells expressed stem cell markers.
      Cells were grown as adherent monolayers, responded to epidermal growth factor,
      and could be expanded indefinitely without growth factors under normal culture
      conditions. They could be frozen and thawed without losing their characteristics.
      In the presence of extracellular matrix and fibroblast growth factor-2 or
      retinoic acid, they acquired neural morphology, formed neurospheres, and
      expressed neural stem cell markers including betaIII tubulin, Sox2, Pax6, Chx10,
      and Notch 1. They also expressed markers of postmitotic retinal neurons,
      including peripherin, recoverin, calretinin, S-opsin, and Brn3. When grafted into
      the subretinal space of dystrophic Royal College of Surgeons rats or neonatal
      Lister hooded rats, immortalized cells migrated into the retina, where they
      expressed various markers of retinal neurons. These observations indicate that
      adult human neural retina harbors a population of cells that express both Muller
      glial and stem cell markers and suggest that these cells may have potential use
      for cell-based therapies to restore retinal function. Disclosure of potential
      conflicts of interest is found at the end of this article.

PMID- 17525240
TI  - The future (r)evolution of preimplantation genetic diagnosis/human leukocyte
      antigen testing: ethical reflections.
AB  - There has been increasing support for combining preimplantation genetic diagnosis
      (PGD) for specific diseases with a test for human leukocyte antigens (HLA)
      because the generation of HLA-matched umbilical cord blood cells may save the
      life of a diseased sibling. To date, this procedure has taken place in the
      context of conceiving another child--PGD/HLA testing type 1. However, it may well
      become possible to perform PGD/HLA testing outside this context, that is, to
      select matched embryos from which embryonic stem cells could be derived and used
      in cell therapy--PGD/HLA testing type 2. A proactive ethical analysis is needed
      and is presented in this article. Although PGD/HLA testing type 1 can be morally
      justified, the risks, pitfalls, and practical limitations of this procedure make
      it necessary to develop alternative strategies. PGD/HLA testing type 2 may
      provide an alternative strategy. From an ethical point of view, the controversial
      issue is that this procedure creates embryos purely for instrumental use.
      However, given the dominant view that the preimplantation embryo has only limited
      moral value, this alternative may be as morally justified as PGD/HLA testing type
      1.

PMID- 17525241
TI  - Full face mask for noninvasive positive-pressure ventilation in patients with
      acute respiratory failure.
AB  - BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) is commonly used to
      improve ventilation and oxygenation in patients with acute respiratory failure
      (ARF). Mask leak and intolerance due to facial discomfort or claustrophobia often
      occur with NPPV and are frequently cited reasons for treatment failure. METHODS:
      Retrospective review of patient records from a tertiary-care referral hospital.
      RESULTS: We report the effectiveness of a full face mask in the application of
      NPPV for 10 nonambulatory patients (mean [SD], 61 [9] years) who had a combined
      total of 13 episodes of ARF. After these patients were unable to receive NPPV
      therapy via the more commonly available nasal or oronasal masks, care was
      provided using full face masks. Eight of 10 patients had hypercapnic respiratory
      failure; 2 patients, hypoxemic respiratory failure. All patients were placed on
      ventilation initially using a bi-level positive airway pressure device.
      Subsequently, patient ventilation was achieved using a Puritan Bennett 7200a
      ventilator for on-line respiratory monitoring. The mean (SD) duration of
      treatment with NPPV was 9.7 (2.7) hours per day for 3.0 (1.6) days. Following
      NPPV via full face mask, the patients' Paco(2) decreased (65 [20] vs 82 [27] mm
      Hg, P=.09) and pH increased significantly (7.36 [0.07] vs 7.26 [0.07], P<.05) in
      less than 2 hours. Moreover, the patients demonstrated decreased respiratory rate
      (18 [7] vs 32 [8] breaths/min, P<.01), heart rate (106 [13] vs 124 [16]
      beats/min, P=.008), and Acute Physiology and Chronic Health Evaluation II scores
      (12 [3] vs 17 [4], P<.005) after NPPV via full face mask. These cardiorespiratory
      alterations occurred as early as 1 hour after NPPV initiation and were maintained
      throughout treatment. Two patients required endotracheal intubation because of
      copious purulent secretions. CONCLUSION: For individuals with hypercapnic
      respiratory failure who cannot tolerate NPPV using nasal or oronasal masks, use
      of full face masks may improve outcomes, allowing physicians to avoid ordering
      endotracheal intubation and mechanical ventilation.

PMID- 17525242
TI  - Does the medical college admission test predict global academic performance in
      osteopathic medical school?
AB  - OBJECTIVE: To investigate the extent to which Medical College Admission Test
      (MCAT) subscores predict the overall academic performance of osteopathic medical
      students. METHODS: We examined the value of MCAT subscores in predicting
      students' global academic performance in osteopathic medical school, as defined
      by grade point average in basic science (basic GPA), clinical instruction
      (clinical GPA), cumulative grade point average (total GPA), and national
      licensing examination scores on the Comprehensive Osteopathic Medical Licensing
      Examination-USA (COMLEX-USA) Level 1 and Level 2. Subjects were 434 osteopathic
      medical students of the Oklahoma State University College of Osteopathic Medicine
      in Tulsa who either graduated or were expected to graduate between the years 1999
      and 2003. Standard, multivariate linear regression analyses were conducted for
      each of the five performance variables to assess the relative importance of MCAT
      subtest scores and cumulative undergraduate GPA (total UGPA) in predicting
      academic performance. RESULTS: Total UGPA was the most important, significant
      predictor (beta=.13-.33) in overall student academic performance for all five
      analyzed variables. Less predictive of overall academic performance (beta=-.01
      .21) were MCAT subcores. However, the MCAT biological sciences subscore was a
      significant predictor of basic GPA (beta=.14), the MCAT physical sciences
      subscore significantly predicted COMLEX-USA Level 1 scores (beta=.15), and the
      MCAT verbal reasoning subscore significantly predicted COMLEX-USA Level 2 scores
      (beta=.21). The subscore for the MCAT writing sample was not a significant
      predictor of overall academic performance. CONCLUSION: Total undergraduate GPA
      had the highest predictive value for academic performance as measured by basic
      GPA, clinical GPA, total GPA, and COMLEX-USA Level 1 and Level 2 scores. The
      present study found MCAT subscores to be of limited predictive value in
      determining global academic performance.

PMID- 17525250
TI  - Adhesion specificities of Plasmodium falciparum-infected erythrocytes involved in
      the pathogenesis of pregnancy-associated malaria.

PMID- 17525249
TI  - The myofibroblast: one function, multiple origins.
AB  - The crucial role played by the myofibroblast in wound healing and pathological
      organ remodeling is well established; the general mechanisms of extracellular
      matrix synthesis and of tension production by this cell have been amply
      clarified. This review discusses the pattern of myofibroblast accumulation and
      fibrosis evolution during lung and liver fibrosis as well as during atheromatous
      plaque formation. Special attention is paid to the specific features
      characterizing each of these processes, including the spectrum of different
      myofibroblast precursors and the distinct pathways involved in the formation of
      differentiated myofibroblasts in each lesion. Thus, whereas in lung fibrosis it
      seems that most myofibroblasts derive from resident fibroblasts, hepatic stellate
      cells are the main contributor for liver fibrosis and media smooth muscle cells
      are the main contributor for the atheromatous plaque. A better knowledge of the
      molecular mechanisms conducive to the appearance of differentiated myofibroblasts
      in each pathological situation will be useful for the understanding of fibrosis
      development in different organs and for the planning of strategies aiming at
      their prevention and therapy.

PMID- 17525251
TI  - Renal hemodynamic, inflammatory, and apoptotic responses to lipopolysaccharide in
      HO-1-/- mice.
AB  - Lipopolysaccharide (LPS) induces the stress-responsive gene heme oxygenase-1 (HO
      1). The present study examined the significance of HO-1 in response to LPS. In HO
      1(-/-) mice, as compared with HO-1(+/+) mice, LPS provoked a greater reduction in
      glomerular filtration rate and renal blood flow, increased renal cytokine
      expression, and increased activation of nuclear factor (NF)-kappaB. Conversely,
      HO-1-overexpressing renal epithelial cells, exposed to LPS, exhibited a blunted
      activation of NF-kappaB and less phosphorylation of its inhibitor, IkappaB. In HO
      1(-/-) mice, as compared with HO-1(+/+) mice, LPS provoked markedly greater
      elevations in serum levels of Th1 cytokines, Th2 cytokines, chemokines, and
      cytokines that stimulate bone marrow progenitors. The liver, a major source of
      serum cytokines, showed an increased activation of NF-kappaB in LPS-treated HO-1(
      /-) mice. In addition, LPS provoked widespread apoptosis of immune cells in the
      spleen and thymus in HO-1(-/-) mice but not in HO-1(+/+) mice. We conclude that
      HO-1 deficiency exhibits a heightened and dysregulated inflammatory response to
      LPS accompanied by greater impairment in renal hemodynamic response and
      widespread apoptosis of immune cells. Because polymorphisms in the HO-1 gene with
      diminished HO activity predispose to human disease, we speculate that our
      findings may be relevant to the clinical outcome in patients with sepsis
      syndromes.

PMID- 17525252
TI  - MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in
      cardiac hypertrophy?
AB  - MicroRNAs (miRNAs) are a recently discovered class of endogenous, small,
      noncoding RNAs that regulate gene expression. Although miRNAs are highly
      expressed in the heart, their roles in heart diseases are currently unclear.
      Using microarray analysis designed to detect the majority of mammalian miRNAs
      identified thus far, we demonstrated that miRNAs are aberrantly expressed in
      hypertrophic mouse hearts. The time course of the aberrant miRNA expression was
      further identified in mouse hearts at 7, 14, and 21 days after aortic banding.
      Nineteen of the most significantly dysregulated miRNAs were further confirmed by
      Northern blot and/or real-time polymerase chain reaction, in which miR-21 was
      striking because of its more than fourfold increase when compared with the sham
      surgical group. Similar aberrant expression of the most up-regulated miRNA, miR
      21, was also found in cultured neonatal hypertrophic cardiomyocytes stimulated by
      angiotensin II or phenylephrine. Modulating miR-21 expression via antisense
      mediated depletion (knockdown) had a significant negative effect on cardiomyocyte
      hypertrophy. The results suggest that miRNAs are involved in cardiac hypertrophy
      formation. miRNAs might be a new therapeutic target for cardiovascular diseases
      involving cardiac hypertrophy such as hypertension, ischemic heart disease,
      valvular diseases, and endocrine disorders.

PMID- 17525253
TI  - Angiotensin II type 1 and type 2 receptors play opposite roles in regulating the
      barrier function of kidney glomerular capillary wall.
AB  - Although angiotensin II (Ang II) type 1 receptor antagonist ameliorates
      proteinuria, its pharmacological mechanism and the differential roles of Ang II
      type 1 receptor (AT1R) and type 2 receptor (AT2R) are not well understood. We
      analyzed the effect of Ang II type 1 receptor antagonist on proteinuria caused by
      antibody against nephrin, a functional molecule of glomerular slit diaphragm and
      dysfunction of which is involved in the development of proteinuria in several
      glomerular diseases. We show here that AT1R antagonist ameliorated proteinuria by
      preventing a reduction in the functional molecules of the slit diaphragm. We also
      analyzed the role of AT1R- or AT2R-mediated actions on the expression of the slit
      diaphragm molecules in an in vivo study of normal rat and in an in vitro study of
      cultured podocytes. AT1R-mediated action hampered the mRNA expression of the slit
      diaphragm molecules, whereas AT2R-mediated action enhanced it. These findings
      indicate that Ang II receptor subtypes play opposite roles in regulating the
      barrier function of glomerular capillary wall and that the enhancement of AT2R
      stimulation may serve as a potential therapeutic strategy for proteinuria.

PMID- 17525254
TI  - SRY-related HMG box 9 regulates the expression of Col4a2 through transactivating
      its enhancer element in mesangial cells.
AB  - Accumulation of alpha1(IV) and alpha2(IV) collagen is one of the characteristic
      pathological changes in glomerulosclerosis. Although the Col4a2 gene is known to
      have a 0.3-kb critical enhancer element with the GAACAAT motif, which
      transcription factor binds and transactivates this motif has not been identified.
      In this study, we found that SRY-related HMG box 9 (SOX9) was bound to the
      GAACAAT motif in the Col4a2 enhancer in vitro and in vivo in mesangial cells.
      SOX9 strongly activated this enhancer when cotransfected with Col4a2 enhancer
      promoter construct in mesangial cells and Swiss/3T3 cells. Mutation in the
      GAACAAT motif eliminated the activation by SOX9. Furthermore, transforming growth
      factor-beta (TGF-beta) treatment induced the expression of SOX9 and Col4a2, and a
      small interfering RNA against SOX9 reduced Col4a2 expression induced by TGF-beta
      treatment in mesangial cells. In vivo, we found that the expression of SOX9 was
      dramatically increased along with the expression of TGF-beta and Col4a2 in mouse
      nephrotoxic nephritis. These results indicate that SOX9 is essential for Col4a2
      expression in mesangial cells and might be involved in the accumulation of
      alpha2(IV) collagen in experimental nephritis.

PMID- 17525255
TI  - Subendothelial heparan sulfate proteoglycans become major L-selectin and monocyte
      chemoattractant protein-1 ligands upon renal ischemia/reperfusion.
AB  - Leukocyte infiltration into inflamed tissues is considered to involve sequential
      steps of rolling over the endothelium, adhesion, and transmigration. In this
      model, the leukocyte adhesion molecule L-selectin and its ligands expressed on
      inflamed endothelial cells are involved in leukocyte rolling. We show that upon
      experimental and human renal ischemia/reperfusion, associated with severe
      endothelial damage, microvascular basement membrane (BM) heparan sulfate
      proteoglycans (HSPGs) are modified to bind L-selectin and monocyte
      chemoattractant protein-1. In an in vitro rolling and adhesion assay, L-selectin
      binding HSPGs in artificial BM induced monocytic cell adhesion under reduced
      flow. We examined the in vivo relevance of BM HSPGs in renal ischemia/reperfusion
      using mice mutated for BM HSPGs perlecan (Hspg2(Delta3/Delta3)), collagen type
      XVIII (Col18a1(-/-)), or both (cross-bred Hspg2(Delta3/Delta3)xCol18a1(-/-)) and
      found that early monocyte/macrophage influx was impaired in
      Hspg2(Delta3/Delta3)xCol18a1(-/-) mice. Finally, we confirmed our observations in
      human renal allograft biopsies, showing that loss of endothelial expression of
      the extracellular endosulfatase HSulf-1 may be a likely mechanism underlying the
      induction of L-selectin- and monocyte chemoattractant protein-1-binding HSPGs
      associated with peritubular capillaries in human renal allograft rejection. Our
      results provide evidence for the concept that not only endothelial but also
      (microvascular) BM HSPGs can influence inflammatory responses.

PMID- 17525256
TI  - Human fetal aorta contains vascular progenitor cells capable of inducing
      vasculogenesis, angiogenesis, and myogenesis in vitro and in a murine model of
      peripheral ischemia.
AB  - Vasculogenesis, the formation of blood vessels in embryonic or fetal tissue
      mediated by immature vascular cells (ie, angioblasts), is poorly understood. We
      report the identification of a population of vascular progenitor cells (hVPCs) in
      the human fetal aorta composed of undifferentiated mesenchymal cells that
      coexpress endothelial and myogenic markers. Under culture conditions that
      promoted cell differentiation, hVPCs gave rise to a mixed population of mature
      endothelial and mural cells when progenitor cells were stimulated with vascular
      endothelial growth factor-A or platelet-derived growth factor-betabeta. hVPCs
      grew as nonadherent cells and, when embedded in a three-dimensional collagen gel,
      reorganized into cohesive cellular cords that resembled mature vascular
      structures. hVPC-conditioned medium contained angiogenic substances (vascular
      endothelial growth factor-A and angiopoietin-2) and strongly stimulated the
      proliferation of endothelial cells. We also demonstrate the therapeutic efficacy
      of a small number of hVPCs transplanted into ischemic limb muscle of
      immunodeficient mice. hVPCs markedly improved neovascularization and inhibited
      the loss of endogenous endothelial cells and myocytes, thus ameliorating the
      clinical outcome from ischemia. We conclude that fetal aorta represents an
      important source for the investigation of the phenotypic and functional features
      of human vascular progenitor cells.

PMID- 17525257
TI  - Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin
      diet: association with increased AGER1 expression.
AB  - Aging is accompanied by increased oxidative stress (OS) and accumulation of
      advanced glycation end products (AGEs). AGE formation in food is temperature
      regulated, and ingestion of nutrients prepared with excess heat promotes AGE
      formation, OS, and cardiovascular disease in mice. We hypothesized that sustained
      exposure to the high levels of pro-oxidant AGEs in normal diets (Reg(AGE))
      contributes to aging via an increased AGE load, which causes AGER1 dysregulation
      and depletion of anti-oxidant capacity, and that an isocaloric, but AGE
      restricted (by 50%) diet (Low(AGE)), would decrease these abnormalities. C57BL6
      male mice with a life-long exposure to a Low(AGE) diet had higher than baseline
      levels of tissue AGER1 and glutathione/oxidized glutathione and reduced plasma 8
      isoprostanes and tissue RAGE and p66(shc) levels compared with mice pair-fed the
      regular (Reg(AGE)) diet. This was associated with a reduction in systemic AGE
      accumulation and amelioration of insulin resistance, albuminuria, and
      glomerulosclerosis. Moreover, lifespan was extended in Low(AGE) mice, compared
      with Reg(AGE) mice. Thus, OS-dependent metabolic and end organ dysfunction of
      aging may result from life-long exposure to high levels of glycoxidants that
      exceed AGER1 and anti-oxidant reserve capacity. A reduced AGE diet preserved
      these innate defenses, resulting in decreased tissue damage and a longer lifespan
      in mice.

PMID- 17525258
TI  - Increased apoptosis in first trimester extravillous trophoblasts from pregnancies
      at higher risk of developing preeclampsia.
AB  - Preeclampsia complicates 5 to 10% of pregnancies and is a leading cause of
      maternal and fetal mortality and morbidity. Although the cause is unknown,
      inadequate invasion and remodeling of maternal uterine arteries by extravillous
      trophoblasts (EVTs) in the first trimester is a common feature. Uterine spiral
      artery resistance as detected by Doppler ultrasound is commonly used in the
      second trimester to identify pregnancies destined to develop preeclampsia.
      Correlation between high uterine resistance and the failure of trophoblast
      invasion has been reported as early as 12 weeks. However, the reason for this
      failure has not been established. Understanding the processes involved would
      significantly improve our diagnostic potential. In this study, we correlated
      increased first trimester uterine artery resistance with a biological abnormality
      in trophoblast function. EVTs derived from high-resistance pregnancies were more
      sensitive to apoptotic stimuli than those from normal-resistance pregnancies.
      Survival of EVTs from high-resistance pregnancies could be increased by nitric
      oxide, whereas inhibition of nitric oxide in cells from normal-resistance
      pregnancies increased apoptotic sensitivity. This predates the onset of symptoms
      by several weeks and provides evidence for a mechanism responsible for the
      incomplete uterine vessel remodeling and the differences in artery resistance
      between preeclamptic and normal pregnancies.

PMID- 17525259
TI  - Control of Pseudomonas aeruginosa skin infections in mice is mast cell-dependent.
AB  - Mast cells (MCs) have recently been shown to be essential for the elicitation of
      efficient immune responses in murine sepsis. To explore whether MCs also
      contribute to the control of bacterial skin infections, we studied skin lesions
      induced by Pseudomonas aeruginosa (PA) in genetically MC-deficient Kit(W)/Kit(W
      v) mice, normal Kit(+/+) mice, and MC-reconstituted Kit(W)/Kit(W-v) mice. PA
      injections resulted in strikingly (>2-fold) larger skin lesions in Kit(W)/Kit(W
      v) mice than in Kit(+/+) mice, which exhibited pronounced MC degranulation at
      infection sites. In addition, neutrophil recruitment following PA injections and
      bacterial clearance from sites of infection was significantly impaired in
      Kit(W)/Kit(W-v) mice compared with Kit(+/+) mice. Notably, the adoptive transfer
      of MCs to the skin of Kit(W)/Kit(W-v) mice before PA infection resulted in normal
      neutrophil accumulation as well as skin lesions comparable with those in Kit(+/+)
      mice in both bacterial burden and size. These findings demonstrate for the first
      time that activated MCs are crucial for the induction of protective innate immune
      responses to bacterial skin infections.

PMID- 17525260
TI  - Interferon-gamma sensitizes resistant Ewing's sarcoma cells to tumor necrosis
      factor apoptosis-inducing ligand-induced apoptosis by up-regulation of caspase-8
      without altering chemosensitivity.
AB  - Ewing's sarcoma cells are highly susceptible to apoptosis via tumor necrosis
      factor apoptosis-inducing ligand (TRAIL). Resistance to TRAIL has been linked to
      deficient expression of caspase-8 in vitro. Here, we report on the status of
      caspase-8 expression in tumors from patients with Ewing's sarcoma, the effect of
      interferon-gamma on caspase-8 expression and apoptosis, and the role of caspase-8
      for TRAIL- and chemotherapy-mediated apoptosis in Ewing's sarcoma. Using
      immunohistochemistry, we show that low expression of caspase-8 is seen in about
      24% of tumors. Interferon-gamma induces expression of caspase-8 at concentrations
      achievable in humans and sensitizes cells to TRAIL. Transfection of wild type but
      not mutant caspase-8 into caspase-8-deficient Ewing's sarcoma cells restored
      sensitivity to TRAIL, indicating that up-regulation of caspase-8 is sufficient to
      restore TRAIL sensitivity. In contrast, no role for caspase-8 in chemotherapy
      induced apoptosis was identified, because 1) transfection of caspase-8 or
      treatment with interferon-gamma did not alter the sensitivity of caspase-8
      deficient cells to chemotherapeutics, 2) application of chemotherapy did not
      select for caspase-8-negative tumor cells in vivo, and 3) the caspase-8 status of
      tumors did not influence survival after chemotherapy-based protocols. In
      conclusion, our data provide a rationale for the inclusion of interferon-gamma in
      upcoming clinical trials with TRAIL.

PMID- 17525261
TI  - Leptin-dependent toll-like receptor expression and responsiveness in
      preadipocytes and adipocytes.
AB  - Leptin, an adipokine mainly produced by adipocytes, has been well characterized
      with regard to its regulatory function on immune cells. Thus the question
      occurred of how adipocytes and preadipocytes interact with the immune system and
      whether or not this communication is regulated by leptin. With the present study
      we evaluated the Toll-like receptor (TLR) expression and TLR ligand-specific
      activation of murine preadipocytes and adipocytes in the presence [wild type
      (WT), 3T3L1] or absence of leptin (ob/ob) or leptin signaling (db/db). The ob/ob
      as well as db/db adipocytes and preadipocytes were characterized by a significant
      up-regulation of TLR1 to -9 expression when compared with WT cells. In WT
      preadipocytes the TLR responsiveness increased during maturation to adipocytes;
      however, stimulation of ob/ob and db/db cells resulted in a 10- to 20-fold higher
      interleukin-6 production. Signaling studies revealed, in addition to the
      increased TLR expression, alterations in the phosphoinositide 3 kinase signaling
      cascade in ob/ob and db/db cells as an explanation for this increased
      responsiveness. In conclusion, the present study indicates the expression and
      responsiveness of TLR1 to -9 in murine preadipocytes as well as adipocytes, both
      of which are strongly regulated by the adipokine leptin. In summary, these data
      further emphasize the role of fat tissue in the immune system.

PMID- 17525262
TI  - Proangiogenic cytokines as hypoxia-dependent factors stimulating migration of
      human hepatic stellate cells.
AB  - Pathological angiogenesis is associated with the fibrogenic progression of
      chronic liver diseases. Experimental data suggest that hypoxia and vascular
      endothelial growth factor (VEGF) may stimulate proliferation and synthesis of
      type I collagen in activated, myofibroblast-like rat hepatic stellate cells
      (HSC/MFs). In this study, we investigated whether hypoxia, recombinant VEGF, or
      angiopoietin 1 (Ang-1) may affect other crucial profibrogenic features. In human
      HSC/MFs, which constitutively express VEGF receptor-1 and -2 (VEGFR-1, VEGFR-2)
      and the Ang-1 receptor Tie-2, exposure to hypoxia, VEGF, or Ang-1 resulted in a
      Ras/Erk-dependent stimulation of chemokinesis and chemotaxis. Migration of human
      HSC/MFs under hypoxic conditions involved up-regulation of VEGF-A, Ang-1, and
      related receptors and was mainly dependent on VEGFR-2 (Flk-1). In specimens from
      either cirrhotic rat livers or from patients with hepatitis C virus-related
      cirrhosis, HSC/MFs expressed proangiogenic factors and related receptors in areas
      of active fibrogenesis (ie, at the leading or lateral edge of developing
      incomplete fibrotic septa). Data presented herein suggest that VEGF and Ang-1 may
      contribute to fibrogenesis by acting as hypoxia-inducible, autocrine, and
      paracrine factors able to recruit myofibroblast-like cells. Moreover, HSC/MFs, in
      addition to their established profibrogenic role, may also contribute to
      neoangiogenesis during chronic hepatic wound healing.

PMID- 17525263
TI  - Attenuation of inflammation and apoptosis by pre- and posttreatment of
      darbepoetin-alpha in acute liver failure of mice.
AB  - In many liver disorders inflammation and apoptosis are important pathogenic
      components, finally leading to acute liver failure. Erythropoietin and its
      analogues are known to affect the interaction between apoptosis and inflammation
      in brain, kidney, and myocardium. The present study aimed to determine whether
      these pleiotropic actions also exert hepatoprotection in a model of acute liver
      injury. C57BL/6J mice were challenged with d-galactosamine (Gal) and Escherichia
      coli lipopolysaccharide (LPS) and studied 6 hours thereafter. Animals were either
      pretreated (24 hours before Gal-LPS exposure) or posttreated (30 minutes after
      Gal-LPS exposure) with darbepoetin-alpha (DPO, 10 mug/kg i.v.). Control mice
      received physiological saline. Administration of Gal-LPS caused systemic cytokine
      release and provoked marked hepatic damage, characterized by leukocyte
      recruitment and microvascular perfusion failure, caspase-3 activation, and
      hepatocellular apoptosis as well as enzyme release and necrotic cell death. DPO
      pretreated and -posttreated mice showed diminished systemic cytokine
      concentrations, intrahepatic leukocyte accumulation, and hepatic perfusion
      failure. Hepatocellular apoptosis was significantly reduced by 50 to 75% after
      DPO pretreatment as well as posttreatment. In addition, treatment with DPO also
      significantly abrogated necrotic cell death and liver enzyme release. In
      conclusion, these observations may stimulate the evaluation of DPO as
      hepatoprotective therapy in patients with acute liver injury.

PMID- 17525264
TI  - Enhanced expression of keratinocyte growth factor and its receptor correlates
      with venous invasion in pancreatic cancer.
AB  - Keratinocyte growth factor (KGF) and KGF receptor (KGFR) have been implicated in
      cancer growth as well as tissue development and repair. In this study, we
      examined whether KGF and KGFR have a role in human pancreatic ductal
      adenocarcinoma (PDAC). KGFR mRNA was expressed in eight pancreatic cancer cell
      lines, whereas the KGF mRNA was detected in seven of the cell lines and was
      absent in MIA PaCa-2 cells. KGFR and KGF immunoreactivity were localized in the
      cancer cells in 41.5 and 34.0% of patients, respectively. There was a significant
      correlation between KGFR or KGF immunoreactivity and venous invasion and a
      significant correlation between the presence of both markers and venous invasion,
      vascular endothelial growth factor (VEGF)-A expression, and poor prognosis.
      Exogenous KGF increased VEGF-A expression and release in MIA PaCa-2 cells, and
      PANC-1 cells stably transfected to overexpress KGF-exhibited increased VEGF-A
      expression. Moreover, short hairpin-KGFR transfection in MIA PaCa-2 cells reduced
      the stimulatory effect of exogenous KGF on VEGF-A expression. Short hairpin-KGF
      transfection in KLM-1 cells reduced VEGF-A expression in the cells. KGFR and KGF
      may act to promote venous invasion and tumor angiogenesis in PDAC, raising the
      possibility that they may serve as novel therapeutic targets in anti-angiogenic
      strategies in PDAC.

PMID- 17525265
TI  - CCR5 deficiency drives enhanced natural killer cell trafficking to and activation
      within the liver in murine T cell-mediated hepatitis.
AB  - Natural killer (NK) cells are innate immune cells that are enriched in the liver,
      but the processes underlying NK cell trafficking to the liver and cellular
      activation within the liver of patients with T cell-mediated liver diseases
      remain poorly defined. Concanavalin A (Con A) hepatitis is a murine model
      mimicking many aspects of human T cell-mediated liver diseases. Here we
      demonstrate that severe hepatitis in CCR5-deficient (KO) mice is associated with
      increased hepatic NK cell recruitment driven by enhanced hepatic production of
      CCL5 acting via CCR1 and by enhanced hepatic NK cell activation relative to that
      observed in wild-type mice after Con A administration. Furthermore, NK cell
      depletion ameliorated severe hepatitis in CCR5 KO mice but did not alter
      hepatitis in wild-type mice after Con A treatment. We propose that in the setting
      of CCR5 deficiency NK cells assume a profound effector role in Con A hepatitis
      via enhanced CCL5-CCR1 driven hepatic recruitment in addition to augmented
      cytokine-driven NK cell activation to produce interferon-gamma. These results
      highlight the potential profound impact of altered chemokine receptor expression
      on the innate immune response in the setting of T cell-mediated hepatitis.

PMID- 17525266
TI  - Chondroitin sulfate proteoglycan but not hyaluronic acid is the receptor for the
      adherence of Plasmodium falciparum-infected erythrocytes in human placenta, and
      infected red blood cell adherence up-regulates the receptor expression.
AB  - A low-sulfated chondroitin sulfate proteoglycan (CSPG) has been shown to be the
      receptor for the adherence of Plasmodium falciparum-infected red blood cells
      (IRBCs) in human placenta. Recently, hyaluronic acid (HA) has been suggested as
      an additional receptor even though IRBC binding to HA and the presence of HA at
      locations where IRBCs adhere in the placenta have not been established. In this
      study, we investigated whether HA is also a receptor for IRBC binding. IRBCs from
      infected placentas as well as those from different laboratory strains could bind
      to CSPG but not to HA. In a cell depletion assay, IRBCs from infected placentas
      could bind quantitatively to CSPG. Although CSPG is present both in the
      intervillous space and on the syncytiotrophoblast surface, HA is absent in these
      locations. These data conclusively demonstrate that CSPG, but not HA, is a
      receptor for IRBC adherence in the placenta. Our data also show, for the first
      time, that the IRBC-binding CSPG in the placenta is of fetal origin and that, in
      P. falciparum-infected placentas, the CSPG level is significantly increased,
      which could exacerbate IRBC adherence and placental pathogenesis. These results
      have important implications for the development of anti-IRBC adhesion-based
      vaccine for pregnancy-associated malaria.

PMID- 17525267
TI  - p150/95 (CD11c/CD18) expression is required for the development of experimental
      autoimmune encephalomyelitis.
AB  - p150/95 (CD11c/CD18, CR4) is a member of the beta(2)-integrin family of adhesion
      molecules and is considered an important phagocytic receptor. The role of p150/95
      in the development of central nervous system demyelinating diseases, including
      multiple sclerosis, remains unexplored. To determine p150/95-mediated mechanisms
      in experimental autoimmune encephalomyelitis (EAE), we performed EAE using CD11c
      deficient (CD11c(-/-)) mice. EAE in CD11c(-/-) mice was significantly attenuated
      and characterized by markedly reduced spinal cord T-cell infiltration and
      interferon-gamma production by these cells. Adoptive transfer of antigen
      restimulated T cells from wild-type to CD11c(-/-) mice produced significantly
      attenuated EAE, whereas transfer of CD11c(-/-) antigen-restimulated T cells to
      control mice induced a very mild, monophasic EAE. T cells from MOG(35-55) peptide
      primed CD11c(-/-) mice displayed an unusual cytokine phenotype with elevated
      levels of interleukin (IL)-2, IL-4, and IL-12 but reduced levels of interferon
      gamma, tumor necrosis factor-alpha, IL-10, IL-17, and transforming growth factor
      beta compared with control mice. Overall, CD11c(-/-) T cells from primed mice
      proliferated comparably to that of control T cells on MOG(35-55) restimulation.
      Our results indicate that expression of p150/95 is critical on both T cells as
      well as other leukocytes for the development of demyelinating disease and may
      represent a novel therapeutic target for multiple sclerosis.

PMID- 17525268
TI  - The cartilage matrix protein subdomain of type VII collagen is pathogenic for
      epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is an acquired bullous disease of the skin
      characterized by IgG autoantibodies against type VII (anchoring fibril) collagen.
      We previously defined four immunodominant antigenic epitopes within the
      noncollagenous 1 (NC1) domain of type VII collagen. In this study, we produced an
      additional recombinant fusion protein from the NC1 domain corresponding to the N
      terminal 227 amino acids (residues 1 to 227), which contains homology with
      cartilage matrix protein (CMP). Using enzyme-linked immunosorbent assay and
      immunoblot analysis, we tested sera from EBA patients (n = 32), bullous systemic
      lupus erythematosus patients (n = 3), bullous pemphigoid patients (n = 15), and
      normal humans (n = 12). Twenty-six of 32 EBA sera and two of three bullous
      systemic lupus erythematosus sera reacted with the CMP domain, whereas none of
      the control sera did. Affinity-purified anti-CMP EBA antibodies injected into
      hairless mice produced the clinical, histological, immunological, and
      ultrastructural features of EBA. F(ab')(2) fragments generated from anti-CMP EBA
      autoantibodies did not induce disease. Our studies provide the first evidence
      that EBA autoantibodies to the CMP subdomain of NC1 are pathogenic and induce
      blister formation. This is the first antigenic epitope on type VII collagen
      demonstrated to be a pathogenic target for EBA autoantibodies.

PMID- 17525269
TI  - The role of platelets in leukocyte recruitment in chronic contact
      hypersensitivity induced by repeated elicitation.
AB  - Platelets have been shown to be important in inflammation, but their role in
      chronic allergic dermatitis remains unclear. To investigate the role of platelets
      in a mouse model of chronic contact hypersensitivity induced by repeated
      elicitation, mice were sensitized and repeatedly elicited in ears with hapten,
      with or without platelet depletion, by administering antiplatelet antibody or
      busulfan. Ear thickness, leukocyte infiltration, serum IgE, and scratching
      behavior significantly decreased in thrombocytopenic mice. cDNA microarray of ear
      tissue showed reduced gene expression associated with Th2 lymphocytes. Flow
      cytometry showed increased P-selectin expression on platelets and an increased
      number of platelet-leukocyte aggregates in blood of repeatedly elicited mice,
      compared with sham-sensitized mice. In thrombocytopenic mice, inflammation was
      restored by platelet infusion, which was blocked by platelets from P-selectin
      deficient mice or by pretreating platelets with anti-P-selectin antibody.
      Moreover, injection of activated platelet supernatant into ears led to increased
      leukocyte infiltration, which was blocked by pretreating platelets with
      antiplatelet compounds or neutralizing several chemokines in the platelet
      supernatant. These results suggest that platelets induce leukocyte recruitment
      into skin by forming platelet-leukocyte aggregates via P-selectin in blood and
      secreting chemokines at inflamed sites. Therefore, controlling platelet activity
      may be useful for treatment of chronic allergic dermatitis.

PMID- 17525270
TI  - Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary
      tumors and breast cancer risk.
AB  - Low-penetrance breast cancer susceptibility alleles seem to play a significant
      role in breast cancer risk but are difficult to identify in human cohorts. A
      genetic screen of 176 N2 backcross progeny of two Trp53(+/-) strains, BALB/c and
      C57BL/6, which differ in their susceptibility to mammary tumors, identified a
      modifier of mammary tumor susceptibility in an approximately 25-Mb interval on
      mouse chromosome 7 (designated SuprMam1). Relative to heterozygotes, homozygosity
      for BALB/c alleles of SuprMam1 significantly decreased mammary tumor latency from
      70.7 to 61.1 weeks and increased risk twofold (P = 0.002). Dmbt1 (deleted in
      malignant brain tumors 1) was identified as a candidate modifier gene within the
      SuprMam1 interval because it was differentially expressed in mammary tissues from
      BALB/c-Trp53(+/-) and C57BL/6-Trp53(+/-) mice. Dmbt1 mRNA and protein was reduced
      in mammary glands of the susceptible BALB/c mice. Immunohistochemical staining
      demonstrated that DMBT1 protein expression was also significantly reduced in
      normal breast tissue from women with breast cancer (staining score, 1.8; n = 46)
      compared with cancer-free controls (staining score, 3.9; n = 53; P < 0.0001).
      These experiments demonstrate the use of Trp53(+/-) mice as a sensitized
      background to screen for low-penetrance modifiers of cancer. The results identify
      a novel mammary tumor susceptibility locus in mice and support a role for DMBT1
      in suppression of mammary tumors in both mice and women.

PMID- 17525271
TI  - Aminoacyl-tRNA synthetase-interacting multifunctional protein 1/p43 controls
      endoplasmic reticulum retention of heat shock protein gp96: its pathological
      implications in lupus-like autoimmune diseases.
AB  - Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1;
      previously known as p43) is a multifunctional protein that was initially found in
      multitRNA synthetase complex. In the present study, screening of the AIMP1
      binding proteins revealed that AIMP1 can form a molecular complex with heat shock
      protein gp96. AIMP1 enhances gp96 dimerization and the interaction between gp96
      and KDEL receptor-1 (KDELR-1), which mediates the retrieval of KDEL-containing
      proteins from Golgi to the endoplasmic reticulum (ER). The interaction between
      gp96 and KDELR-1 was reduced in AIMP1-deficient cells, and this disturbed ER
      retention of gp96 and increased its cell surface localization. Moreover, this
      localization of gp96 at the cell surface was suppressed by its interaction with
      AIMP1 and enhanced by the depletion of endogenous AIMP1. In addition, AIMP1
      deficient mice showed dendritic cell activation attributable to increased gp96
      surface presentation and lupus-like autoimmune phenotypes. These results suggest
      that AIMP1 acts as a regulator of the ER retention of gp96 and provide a new
      perspective of the regulatory mechanism underlying immune stimulation by gp96.

PMID- 17525272
TI  - Focal adhesion kinase controls pH-dependent epidermal barrier homeostasis by
      regulating actin-directed Na+/H+ exchanger 1 plasma membrane localization.
AB  - Ubiquitously expressed focal adhesion kinase (FAK), linked to multiple
      intracellular signaling pathways, has previously been shown to control cell
      motility, invasion, proliferation, and survival. Using mice with a keratinocyte
      restricted deletion of fak (FAK(K5 KO)), we report here a novel role for FAK:
      maintenance of adult epidermal permeability barrier homeostasis. Abundant lacunae
      of unprocessed lipids in stratum corneum (SC) of FAK(K5 KO) mice and delayed
      barrier recovery pointed to malfunction of pH-dependent enzymes active in
      extracellular space of SC. Measuring the SC pH gradient showed significantly more
      neutral pH values in FAK(K5 KO) mice, suggesting the importance of FAK for
      acidification. Moreover, normal functions were restored when FAK(K5 KO) mice were
      exposed to a surface pH typical of mouse SC (pH = 5.5). Baseline levels and
      response to barrier disruption of secretory phospholipase A2 isoforms, enzymes
      that mediate generation of free fatty acids in epidermis, appeared similar in
      both FAK(K5 KO) and control littermates. We found that the critical SC
      acidification regulator Na(+)/H(+) exchanger 1 failed to localize to the plasma
      membrane in FAK-deficient keratinocytes both in vivo and in vitro. Thus, for
      plasma membrane localization in terminally differentiated keratinocytes,
      Na(+)/H(+) exchanger 1 requires an intact actin cytoskeleton, which is impaired
      in FAK-deficient cells.

PMID- 17525273
TI  - Vacuolar leukoencephalopathy with widespread astrogliosis in mice lacking
      transcription factor Nrf2.
AB  - NFE2-related factor 2 (Nrf2), an oxidant-activated CNC bZip transcription factor,
      has been implicated in defense against oxidative stress and chemical insults in a
      range of cell and tissue types, including the central nervous system. Here, we
      report that deletion of the Nrf2 gene in mice caused vacuolar (spongiform)
      leukoencephalopathy with widespread astrogliosis. The leukoencephalopathy was
      present in all Nrf2-null mice more than 10 months of age, was characterized by
      vacuolar degeneration involving all major brain regions, and was most apparent in
      the white tracts of the cerebellum and pons. Vacuolar degeneration in white
      tracts was attributable to myelin unwinding and intramyelinic cysts, and double
      label immunofluorescence for 4-hydroxy-2-nonenal and myelin basic protein
      localized free-radical-induced oxidative damage to the myelin sheath. Moreover,
      the brains of Nrf2-null mice exhibited widespread astrocyte activation with
      profusion of glial fibrillary acidic protein-immunoreactive glial processes. The
      study uncovered a possible physiological role for Nrf2 in maintaining central
      nervous system myelin. If this role is confirmed, it may suggest new approaches
      to treating genetically and chemically induced myelin degenerative diseases.

PMID- 17525274
TI  - Sperm abnormalities in heterozygous acid sphingomyelinase knockout mice reveal a
      novel approach for the prevention of genetic diseases.
AB  - Acid sphingomyelinase knockout mice are a model of the inherited human disorder
      types A and B Niemann-Pick disease. Herein, we show that heterozygous (ASMKO(+/
      )) mice have two distinct sperm populations resembling those found in normal and
      mutant animals, respectively, and that these two populations could be
      distinguished by their morphology, ability to undergo capacitation or the
      acrosome reaction, and/or mitochondrial membrane potential (MMP). The abnormal
      morphology of the mutant sperm could be normalized by demembranation with
      detergents or by the addition of recombinant acid sphingomyelinase to the culture
      media, and the corrected sperm also had an enhanced fertilization capacity.
      Methods were then explored to enrich for normal sperm from the mixed ASMKO(+/-)
      population, and flow cytometric sorting based on MMP provided the best results.
      In vitro fertilization was performed using ASMKO(+/-) oocytes and sperm before
      and after MMP sorting, and it was found that the sorted sperm produced
      significantly more wild-type pups than nonsorted sperm. Sperm sorting is much
      less invasive and more cost-effective than egg isolation, and offers several
      advantages over the existing assisted reproduction options for Niemann-Pick
      disease carrier couples. It therefore could have a major impact on the prevention
      of this and perhaps other genetic diseases.

PMID- 17525275
TI  - Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the
      skin.
AB  - In this study, we examined ErbB1 signaling in human basal and squamous cell
      carcinomas (BCC and SCC) of the skin in vivo. We used enzyme-linked immunosorbent
      assay, laser capture microdissection-coupled real-time reverse transcriptase
      polymerase chain reaction, and immunohistochemistry to assess expression and
      activation levels of ErbB1 protein, ligands, and potential downstream effectors,
      in BCC and SCC tumors, stroma, and adjacent epidermis. Although total ErbB1
      protein and mRNA were similar in cancerous and normal skin, we found that ErbB1
      activation (phospho-Tyr(1068)) was greater in bulk SCC versus BCC or normal skin.
      In addition, three ErbB1 ligand transcripts (amphiregulin, heparin-binding
      epidermal growth factor-like growth factor, and transforming growth factor-alpha)
      were up-regulated in tumor cells of SCC but not BCC. Expression of these ligands
      was also increased in asymptomatic epidermis adjacent to both SCC and BCC,
      relative to normal skin. Interestingly, betacellulin transcript levels were
      inversely regulated compared with the other ligands. Consistently, downstream
      ErbB1 effectors (Erk1/2 and Akt) were activated in tumor cells of SCC but not of
      BCC and in adjacent epidermis of both BCC and SCC. These results demonstrate that
      ErbB1 signaling is hyperactive in tumor cells of SCC but not of BCC and in nearby
      asymptomatic epidermis of both tumor types. Our results suggest that targeting
      ErbB1 signaling might be of benefit in the treatment of SCC.

PMID- 17525276
TI  - Prostate cancer-associated membrane type 1-matrix metalloproteinase: a pivotal
      role in bone response and intraosseous tumor growth.
AB  - Membrane type 1-matrix metalloproteinase (MT1-MMP) is a major mediator of
      collagen I degradation. In human samples, we show that prostate cancer cells in
      skeletal metastases consistently express abundant MT1-MMP protein. Because
      prostate cancer bone metastasis requires remodeling of the collagen-rich bone
      matrix, we investigated the role of cancer cell-derived MT1-MMP in an
      experimental model of tumor-bone interaction. MT1-MMP-deficient LNCaP human
      prostate cancer cells were stably transfected with human wild-type MT1-MMP
      (MT1wt). Furthermore, endogenous MT1-MMP was down-regulated by small interfering
      RNA in DU145 human prostate cancer cells. Intratibial tumor injection in severe
      combined immunodeficient mice was used to simulate intraosseous growth of
      metastatic tumors. LNCaP-MT1wt cells produced larger osseous tumors than Neo
      control cells and induced osteolysis, whereas DU145 MT1-MMP-silenced
      transfectants induced osteogenic changes. In vitro assays showed that MT1wt
      overexpression enhanced collagen I degradation, whereas MT1-MMP-silencing did the
      opposite, suggesting that tumor-derived MT1-MMP may contribute directly to bone
      remodeling. LNCaP-MT1wt-derived conditioned medium stimulated in vitro
      multinucleated osteoclast formation. This effect was inhibited by
      osteoprotegerin, a decoy receptor for receptor activator of nuclear factor kappaB
      ligand, and by 4-[4-(methanesulfonamido) phenoxy] phenylsulfonyl methylthiirane,
      an MT1-MMP inhibitor. Our findings are consistent with the hypothesis that
      prostate cancer-associated MT1-MMP plays a direct and/or indirect role in bone
      matrix degradation, thus favoring intraosseous tumor expansion.

PMID- 17525277
TI  - Down-regulation of WAVE3, a metastasis promoter gene, inhibits invasion and
      metastasis of breast cancer cells.
AB  - The expression of WAVE3, an actin-cytoskeleton and reorganization protein, is
      elevated in malignant human breast cancer, yet the role of WAVE3 in promoting
      tumor progression remains undefined. We have recently shown that knockdown of
      WAVE3 expression in human breast adenocarcinoma MDA-MB-231 cells using small
      interfering RNA resulted in a significant reduction of cell motility, migration,
      and invasion, which correlated with a reduction in the levels of active p38
      mitogen-activated protein kinase. Here, we investigated the effect of stable
      suppression of WAVE3 by short hairpin RNA on tumor growth and metastasis in
      xenograft models. Breast cancer MDA-MB-231 cells expressing short hairpin RNA to
      WAVE3 (shWAVE3) showed a significant reduction in Matrigel invasion and formation
      of lung colonies after tail-vein injection in SCID mice. In the orthotopic model,
      we observed a reduction in growth rate of the primary tumors, as well as in the
      metastases to the lungs. We also show that suppression of p38 mitogen-activated
      protein kinase activity by dominant-negative p38 results in comparable phenotypes
      to the knockdown of WAVE3. These studies provide direct evidence that the WAVE3
      p38 pathway contributes to breast cancer progression and metastasis.

PMID- 17525278
TI  - Mice with enhanced macrophage angiotensin-converting enzyme are resistant to
      melanoma.
AB  - Angiotensin-converting enzyme (ACE) is a peptidase responsible for the cleavage
      of angiotensin I and several other peptides. Here, gene targeting was used to
      switch control of the ACE locus from the endogenous promoter to the macrophage
      specific c-fms promoter. Challenge of these mice, called ACE 10/10, with the
      aggressive mouse melanoma cell line B16 showed that they are remarkably resistant
      to tumor growth. Tumor resistance was seen after challenge with different
      melanoma cell lines and in mice with different genetic backgrounds. Histological
      study of the tumors that did grow in ACE 10/10 mice showed an enhanced
      inflammatory response. ACE 10/10 mice had increased numbers of tumor epitope
      specific CD8(+) T cells after challenge with melanoma or lymphoma. ACE 10/10
      macrophages showed increased production of interleukin-12 and nitric oxide but
      reduced interleukin-10. Engraftment of wild-type mice with ACE 10/10 bone marrow
      transferred B16 tumor resistance. Injection of B16 tumors with ACE 10/10
      macrophages also reduced tumor growth. ACE 10/10 mice may define a new means of
      enhancing the immune response, which may be potentially useful in several human
      clinical situations.

PMID- 17525279
TI  - Evidence for a role of tumor-derived laminin-511 in the metastatic progression of
      breast cancer.
AB  - Most studies investigating laminins (LMs) in breast cancer have focused on LM-111
      or LM-332. Little is known, however, about the expression and function of alpha5
      chain-containing LM-511/521 during metastatic progression. Expression of LM
      511/521 subunits was examined in genetically related breast tumor lines and
      corresponding primary tumors and metastases in a syngeneic mouse model using real
      time quantitative polymerase chain reaction, in situ hybridization, and
      immunohistochemistry. The results from our investigation indicate that LM-511
      rather than LM-111, -332, or -521 correlates with metastatic potential in mouse
      mammary tumors. LM-511 was a potent adhesive substrate for both murine and human
      breast carcinoma cells and promoted strong haptotactic responses in metastatic
      lines. Haptotaxis was mediated by alpha3 integrin in both MCF-7 and MDA-MB-231
      cells and was strongly inhibited by blocking antibodies against this integrin
      subunit. However, whereas nonmetastatic MCF-7 cells migrated toward LM-511
      primarily via alpha3beta1 integrin, results from antibody perturbation
      experiments and flow cytometry analysis suggest that this response is mediated by
      an as yet unidentified alpha3beta integrin heterodimer (other than alpha3beta1)
      in MDA-MB-231 cells. These results are consistent with earlier reports
      implicating alpha3 integrins in breast cancer progression and support the role of
      LM-511 as a functional substrate regulating breast cancer metastasis.

PMID- 17525280
TI  - Interleukin-6 receptor-mediated activation of signal transducer and activator of
      transcription-3 (STAT3) promotes choroidal neovascularization.
AB  - Interleukin (IL)-6, a potent proinflammatory cytokine, is suggested to be a risk
      factor for choroidal neovascularization (CNV) because of its increased levels in
      the serum of patients with age-related macular degeneration; however, the role of
      IL-6 in CNV has not been defined. The present study reveals the critical
      contribution of IL-6 signaling and its downstream STAT3 pathway to the murine
      model of laser-induced CNV. CNV induction by laser treatment stimulated IL-6
      expression in the retinal pigment epithelium-choroid complex, and antibody-based
      blockade of IL-6 receptor or genetic ablation of IL-6 led to significant
      suppression of CNV. CNV generation was accompanied by STAT3 activation in
      choroidal endothelial cells and macrophages, and IL-6 receptor blockade resulted
      in selectively inhibited phosphorylation of STAT3 but not extracellular signal
      regulated kinase 1/2. Consistently, pharmacological blockade of STAT3 pathway
      also suppressed CNV. In addition, IL-6 receptor neutralization led to significant
      inhibition of the in vivo and in vitro expression of inflammation-related
      molecules including monocyte chemotactic protein, intercellular adhesion molecule
      1, and vascular endothelial growth factor, and of macrophage infiltration into
      CNV. These results indicate the significant involvement of IL-6 receptor-mediated
      activation of STAT3 inflammatory pathway in CNV generation, suggesting the
      possibility of IL-6 receptor blockade as a therapeutic strategy to suppress CNV
      associated with age-related macular degeneration.

PMID- 17525281
TI  - Pigment epithelium-derived factor inhibits neointimal hyperplasia after vascular
      injury by blocking NADPH oxidase-mediated reactive oxygen species generation.
AB  - Pigment epithelium-derived factor (PEDF) inhibits cytokine-induced endothelial
      cell activation through its antioxidative properties. However, the effect of PEDF
      on restenosis remains to be elucidated. Because the pathophysiological feature of
      restenosis is characterized by increased superoxide formation and accumulation of
      smooth muscle cells (SMCs), PEDF may inhibit this process via suppression of
      reactive oxygen species generation. We investigated here whether PEDF could
      prevent neointimal formation after balloon injury. PEDF levels were decreased in
      balloon-injured arteries. Adenoviral vector encoding human PEDF (Ad-PEDF)
      prevented neointimal formation. Expression and superoxide generation of the
      membrane components of NADPH oxidase, p22(phox) and gp91(phox), in the neointima
      were also suppressed by Ad-PEDF. Ad-PEDF reduced G(1) cyclin (cyclin D1 and E)
      expression and increased p27, a cyclin-dependent kinase inhibitor. In vitro, PEDF
      inhibited platelet-derived growth factor-BB-induced SMC proliferation and
      migration by blocking reactive oxygen species generation through suppression of
      NADPH oxidase activity via down-regulation of p22(PHOX) and gp91(PHOX). PEDF down
      regulated G(1) cyclins and up-regulated p27 levels in platelet-derived growth
      factor-BB-exposed SMCs as well. These results demonstrate that PEDF could inhibit
      neointimal formation via suppression of NADPH oxidase-mediated reactive oxygen
      species generation. Our present study suggests that substitution of PEDF may be a
      novel therapeutic strategy for restenosis after balloon angioplasty.

PMID- 17525282
TI  - Human placental hypoxia-inducible factor-1alpha expression correlates with
      clinical outcomes in chronic hypoxia in vivo.
AB  - Placental hypoxia is causally implicated in fetal growth restriction and
      preeclampsia, with both occurring more frequently at high altitude (>2700 m; HA).
      The nuclear transcription factor hypoxia-inducible factor (HIF) may facilitate
      placental oxygen transport at HA by increasing erythropoiesis and placental
      angiogenesis. We therefore investigated HIF expression and its regulatory
      mechanisms in placentas from normal pregnancies at high (3100 m), moderate (1600
      m), and sea level (75 m) altitudes. Moderate-altitude and sea level placentas did
      not differ, but HIF-1alpha and the von Hippel-Lindau tumor suppressor protein
      were overexpressed in HA placentas. The ability of von Hippel-Lindau tumor
      suppressor protein to form the E3 ubiquitin protein ligase complex, required for
      HIF-1alpha degradation, was unaltered in HA placentas. mRNA for factor-inhibiting
      HIF, a negative modulator of HIF-1alpha transactivation, was increased, but
      protein levels were diminished. Elevated HIF-1alpha likely contributed to the
      significant increase we report in HIF-1alpha downstream target proteins,
      transforming growth factor beta3 in the placenta, and vascular endothelial growth
      factor and erythropoietin in the maternal circulation. These circulating markers
      and lowered birth to placental weight ratios correlated with increased HIF
      1alpha, thereby linking molecular and systemic physiological data. The HA
      response to chronic hypoxia resembles preeclampsia in several aspects,
      illustrating the utility of the HA model in understanding placental pathologies.

PMID- 17525285
TI  - ATF2 impairs glucocorticoid receptor-mediated transactivation in human CD8+ T
      cells.
AB  - Chronic inflammatory diseases often have residual CD8(+) T-cell infiltration
      despite treatment with systemic corticosteroids, which suggests divergent steroid
      responses between CD4(+) and CD8(+) cells. To examine steroid sensitivity,
      dexamethasone (DEX)-induced histone H4 lysine 5 (K5) acetylation and
      glucocorticoid receptor alpha (GCR alpha) translocation were evaluated. DEX
      treatment for 6 hours significantly induced histone H4 K5 acetylation in normal
      CD4(+) cells (P = .001) but not in CD8(+) cells. DEX responses were functionally
      impaired in CD8(+) compared with CD4(+) cells when using mitogen-activated
      protein kinase phosphatase (1 hour; P = .02) and interleukin 10 mRNA (24 hours; P
      = .004) induction as a readout of steroid-induced transactivation. Normal DEX
      induced GCR alpha nuclear translocation and no significant difference in GCR
      alpha and GCR beta mRNA expression were observed in both T-cell types. In
      addition, no significant difference in SRC-1, p300, or TIP60 expression was
      found. However, activating transcription factor-2 (ATF2) expression was
      significantly lower in CD8(+) compared with CD4(+) cells (P = .009). Importantly,
      inhibition of ATF2 expression by small interfering RNA in CD4(+) cells resulted
      in inhibition of DEX-induced transactivation in CD4(+) cells. The data indicate
      refractory steroid-induced transactivation but similar steroid-induced
      transrepression of CD8(+) cells compared with CD4(+) cells caused by decreased
      levels of the histone acetyltransferase ATF2.

PMID- 17525286
TI  - Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial
      hemophagocytic lymphohistiocytosis 4 (FHL4) patients.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) is typically an early onset,
      fatal disease characterized by a sepsislike illness with cytopenia,
      hepatosplenomegaly, and deficient lymphocyte cytotoxicity. Disease-causing
      mutations have been identified in genes encoding perforin (PRF1/FHL2), Munc13-4
      (UNC13D/FHL3), and syntaxin-11 (STX11/FHL4). In contrast to mutations leading to
      loss of perforin and Munc13-4 function, it is unclear how syntaxin-11 loss-of
      function mutations contribute to disease. We show here that freshly isolated,
      resting natural killer (NK) cells and CD8(+) T cells express syntaxin-11. In
      infants, NK cells are the predominant perforin-containing cell type. NK cells
      from FHL4 patients fail to degranulate when encountering susceptible target
      cells. Unexpectedly, IL-2 stimulation partially restores degranulation and
      cytotoxicity by NK cells, which could explain the less severe disease progression
      observed in FHL4 patients, compared with FHL2 and FHL3 patients. Since the
      effector T-cell compartment is still immature in infants, our data suggest that
      the observed defect in NK-cell degranulation may contribute to the
      pathophysiology of FHL, that evaluation of NK-cell degranulation in suspected FHL
      patients may facilitate diagnosis, and that these new insights may offer novel
      therapeutic possibilities.

PMID- 17525287
TI  - A2A adenosine receptors and C/EBPbeta are crucially required for IL-10 production
      by macrophages exposed to Escherichia coli.
AB  - We recently showed that A(2A) adenosine receptor activation by endogenous
      adenosine contributes to interleukin-10 (IL-10) production in polymicrobial
      sepsis. Here we investigated the molecular mechanisms underpinning this
      interaction between adenosine receptor signaling and infection by exposing
      macrophages to Escherichia coli. We demonstrated using receptor knockout mice
      that A(2A) receptor activation is critically required for the stimulatory effect
      of adenosine on IL-10 production by E coli-challenged macrophages, whereas A(2B)
      receptors have a minor role. The stimulatory effect of adenosine on E coli
      induced IL-10 production did not require toll-like receptor 4 (TLR4) or MyD88,
      but was blocked by p38 inhibition. Using shRNA we demonstrated that TRAF6 impairs
      the potentiating effect of adenosine. Measuring IL-10 mRNA abundance and
      transfection with an IL-10 promoter-luciferase construct indicated that E coli
      and adenosine synergistically activate IL-10 transcription. Sequential deletion
      analysis and site-directed mutagenesis of the IL-10 promoter revealed that a
      region harboring C/EBP binding elements was responsible for the stimulatory
      effect of adenosine on E coli-induced IL-10 promoter activity. Adenosine
      augmented E coli-induced nuclear accumulation and DNA binding of C/EBPbeta.
      C/EBPbeta-deficient macrophages failed to produce IL-10 in response to adenosine
      and E coli. Our results suggest that the A(2A) receptor-C/EBPbeta axis is
      critical for IL-10 production after bacterial infection.

PMID- 17525288
TI  - Multipotent cells can be generated in vitro from several adult human organs
      (heart, liver, and bone marrow).
AB  - The aims of our study were to verify whether it was possible to generate in
      vitro, from different adult human tissues, a population of cells that behaved, in
      culture, as multipotent stem cells and if these latter shared common properties.
      To this purpose, we grew and cloned finite cell lines obtained from adult human
      liver, heart, and bone marrow and named them human multipotent adult stem cells
      (hMASCs). Cloned hMASCs, obtained from the 3 different tissues, expressed the
      pluripotent state-specific transcription factors Oct-4, NANOG, and REX1,
      displayed telomerase activity, and exhibited a wide range of differentiation
      potential, as shown both at a morphologic and functional level. hMASCs maintained
      a human diploid DNA content, and shared a common gene expression signature,
      compared with several somatic cell lines and irrespectively of the tissue of
      isolation. In particular, the pathways regulating stem cell self
      renewal/maintenance, such as Wnt, Hedgehog, and Notch, were transcriptionally
      active. Our findings demonstrate that we have optimized an in vitro protocol to
      generate and expand cells from multiple organs that could be induced to acquire
      morphologic and functional features of mature cells even embryologically not
      related to the tissue of origin.

PMID- 17525289
TI  - Heat shock protein inhibition is associated with activation of the unfolded
      protein response pathway in myeloma plasma cells.
AB  - Plasma cells producing high levels of paraprotein are dependent on the unfolded
      protein response (UPR) and chaperone proteins to ensure correct protein folding
      and cell survival. We hypothesized that disrupting client-chaperone interactions
      using heat shock protein 90 (Hsp90) inhibitors would result in an inability to
      handle immunoglobulin production with the induction of the UPR and myeloma cell
      death. To study this, myeloma cells were treated with Hsp90 inhibitors as well as
      known endoplasmic reticulum stress inducers and proteasome inhibitors. Treatment
      with thapsigargin and tunicamycin led to the activation of all 3 branches of the
      UPR, with early splicing of XBP1 indicative of IRE1 activation, upregulation of
      CHOP consistent with ER resident kinase (PERK) activation, and activating
      transcription factor 6 (ATF6) splicing. 17-AAG and radicicol also induced
      splicing of XBP1, with the induction of CHOP and activation of ATF6, whereas
      bortezomib resulted in the induction of CHOP and activation of ATF6 with minimal
      effects on XBP1. After treatment with all drugs, expression levels of the
      molecular chaperones BiP and GRP94 were increased. All drugs inhibited
      proliferation and induced cell death with activation of JNK and caspase cleavage.
      In conclusion, Hsp90 inhibitors induce myeloma cell death at least in part via
      endoplasmic reticulum stress and the UPR death pathway.

PMID- 17525292
TI  - Altered respiratory pattern and hypoxic response in transgenic newborn mice
      lacking the tachykinin-1 gene.
AB  - Substance P is known to be involved in respiratory rhythm and central pattern
      generating mechanisms, especially during early development. We therefore studied
      respiratory responses in transgenic newborn mice (Tac1(-/-)) lacking substance P
      and neurokinin A (NKA). In vivo, the effects of intermittent isocapnic hypoxia
      (IH) and hypercapnia were studied using whole body flow plethysmography at P2-3
      and P8-10. In vitro, anoxic responses and the effects of hypocapnic and
      hypercapnic conditions were studied in brain stem-spinal cord preparations (C4
      activity) at P2. Hypoxic challenge considerably modified the respiratory activity
      in transgenic mice displayed in vivo as an attenuated increase in tidal volume
      during IH. Transgenic mice also showed a more prominent posthypoxic frequency
      decline in vivo, and posthypoxic neuronal arrests appeared more often in vitro.
      We recognized two types of sigh activity: with or without a following pause.
      During IH, the amount of sighs with a pause decreased and those without
      increased, a redistribution that became stronger with age only in controls.
      Intermittent anoxia induced long-term facilitation effects in controls, but not
      in Tac1(-/-) animals, manifested as an increase in burst frequency in vitro and
      by an augmentation of ventilation during posthypoxic periods in vivo. Thus our
      data demonstrate that a functional substance P/NKA system is of great importance
      for the generation of an adequate respiratory response to hypoxic provocation in
      newborn mice and during early maturation. It also indicates that substance P
      (and/or NKA) is involved in the development of the plasticity of the respiratory
      system.

PMID- 17525293
TI  - Airway mechanoreceptor deactivation.
AB  - Airway sensors play an important role in control of breathing. Recently, it was
      found that pulmonary slowly adapting stretch receptors (SARs) cease after a brief
      excitation following sodium pump blockade by ouabain. This deactivation can be
      explained by overexcitation. If this is true, mechanical stimulation of the SARs
      should also lead to a deactivation. In this study, we recorded unit activity of
      the SARs in anesthetized, open-chest, and mechanically ventilated rabbits and
      examined their responses to lung inflation at different constant pressures. Forty
      seven of 137 units had a clear deactivation during the lung inflation. The
      deactivation threshold varied from unit to unit. For a given unit, the higher the
      inflation pressure, the sooner the deactivation occurs. For example, the SARs
      deactivated at 3.0 +/- 0.3 and 4.8 +/- 0.4 s when the lungs were inflated to
      constant pressures of 30 and 20 cmH(2)O, respectively (n = 25, P < 0.0001). The
      units usually ceased after a brief intense discharge. In some units, their
      activity shifted to a lower level, indicating a pacemaker switching. Our results
      support the notion that SARs deactivate due to overexcitation.

PMID- 17525294
TI  - Take two NSAIDs and call on your satellite cells in the morning.

PMID- 17525295
TI  - No physical activity or exercise is not an option.

PMID- 17525296
TI  - Flow-induced shear strain in intima of porcine coronary arteries.
AB  - The in vivo circumferential strain has a small variation throughout the vascular
      system (aorta to arterioles). The axial strain has also been shown to be nearly
      the same as the circumferential strain under physiological loading. Since the
      endothelium is mechanically much softer than the media-adventitia in healthy
      arteries, the porcine intima was considered as a mechanically distinct layer from
      the media-adventitia in a two-layer computational model. Based on the simulation
      result, we hypothesize that the flow-induced shear strain in intima can be of
      similar value as the pressure-induced circumferential strain in healthy coronary
      arteries, even though the shear stress is orders of magnitude smaller than the
      circumferential stress. The nearly isotropic deformation (circumferential, axial,
      and shear strains) may have important implications for mechanical homeostasis of
      endothelial cells, mechanotransduction, growth, and remodeling of blood vessels.

PMID- 17525297
TI  - Altered biomechanical properties of carotid arteries in two mouse models of
      muscular dystrophy.
AB  - Muscular dystrophy is characterized by skeletal muscle weakness and wasting, but
      little is known about possible alterations to the vasculature. Many muscular
      dystrophies are caused by a defective dystrophin-glycoprotein complex (DGC),
      which plays an important role in mechanotransduction and maintenance of
      structural integrity in muscle cells. The DGC is a group of membrane-associated
      proteins, including dystrophin and sarcoglycan-delta, that helps connect the
      cytoskeleton of muscle cells to the extracellular matrix. In this paper, mice
      lacking genes encoding dystrophin (mdx) or sarcoglycan-delta (sgcd-/-) were
      studied to detect possible alterations to vascular wall mechanics. Pressure
      diameter and axial force-length tests were performed on common carotid arteries
      from mdx, sgcd-/-, and wild-type mice in active (basal) and passive smooth muscle
      states, and functional responses to three vasoactive compounds were determined at
      constant pressure and length. Apparent biomechanical differences included the
      following: mdx and sgcd-/- arteries had decreased distensibilities in pressure
      diameter tests, with mdx arteries exhibiting elevated circumferential stresses,
      and mdx and sgcd-/- arteries generated elevated axial loads and stresses in axial
      force-length tests. Interestingly, however, mdx and sgcd-/- arteries also had
      significantly lower in vivo axial stretches than did the wild type. Accounting
      for this possible adaptation largely eliminated the apparent differences in
      circumferential and axial stiffness, thus suggesting that loss of DGC proteins
      may induce adaptive biomechanical changes that can maintain overall wall
      mechanics in response to normal loads. Nevertheless, there remains a need to
      understand better possible vascular adaptations in response to sustained altered
      loads in patients with muscular dystrophy.

PMID- 17525298
TI  - Geldanamycin inhibits hemorrhage-induced increases in caspase-3 activity: role of
      inducible nitric oxide synthase.
AB  - Hemorrhage has been shown to increase inducible nitric oxide synthase (iNOS) and
      deplete ATP levels in tissues and geldanamycin limits both processes. Moreover,
      it is evident that inhibition of iNOS reduces caspase-3 and increases survival.
      Thus we sought to identify the molecular events responsible for the beneficial
      effect of geldanamycin. Hemorrhage in mice significantly increased caspase-3
      activity and protein while treatment with geldanamycin significantly limited
      these increases. Similarly, geldanamycin inhibited increases in proteins forming
      the apoptosome (a complex of caspase-9, cytochrome c, and Apaf-1). Modulation of
      the expression of iNOS by iNOS gene transfection or siRNA treatment demonstrated
      that the level of iNOS correlates with caspase-3 activity. Our data indicate that
      geldanamycin limits caspase-3 expression and protects from organ injury by
      suppressing iNOS expression and apoptosome formation. Geldanamycin, therefore,
      may prove useful as an adjuvant in fluids used to treat patients suffering blood
      loss.

PMID- 17525299
TI  - Regulation of protease-activated receptor (PAR) 1 and PAR4 signaling in human
      platelets by compartmentalized cyclic nucleotide actions.
AB  - Thrombin potently regulates human platelets by the G protein-coupled receptors
      protease-activated receptor (PAR) 1 and PAR4. Platelet activation by thrombin and
      other agonists is broadly inhibited by prostacyclin and nitric oxide acting
      through adenylyl and guanylyl cyclases to elevate cAMP and cGMP levels,
      respectively. Using forskolin and YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1
      benzylindazole] to selectively activate the adenylyl and guanylyl cyclases,
      respectively, and the membrane-permeable analogs N(6),2'-O-dibutyryladenosine-3'
      5'-cAMP (dibutyryl-cAMP) and 8-(4-parachlorophenylthoi)-cGMP (8-pCPT-cGMP), we
      sought to identify key antiplatelet steps for cyclic nucleotide actions in
      blocking platelet activation by PAR1 versus PAR4. Platelet aggregation by PAR1 or
      PAR4 was inhibited with similar EC(50) of 1.2 to 2.1 microM forskolin, 31 to 33
      microM YC-1, 57 to 150 microM dibutyryl-cAMP, and 220 to 410 microM 8-pCPT-cGMP.
      There was a marked left shift in the inhibitory potencies of forskolin and YC-1
      for alpha-granule release and glycoprotein IIbIIIa/integrin alphaIIbbeta3
      activation (i.e., EC(50) of 1-60 and 40-1300 nM, respectively) that was not
      observed for dibutyryl-cAMP and 8-pCPT-cGMP (i.e., EC(50) of 200-600 and 40-140
      microM, respectively). This inhibition was essentially instantaneous, and
      measurements of cyclic nucleotide levels and kinase activities support a model of
      compartmentation involving the cyclic nucleotide effectors and regulators and the
      key molecular targets for this platelet inhibition. The different sensitivities
      of PAR1 and PAR4 to inhibition of calcium mobilization and dense granule release
      identify key antiplatelet steps for cyclic nucleotide actions and are consistent
      with the signaling models for these receptors. Specifically, PAR4 inhibition
      depends on the regulation of both calcium mobilization and dense granule release,
      and PAR1 inhibition depends predominantly on the regulation of dense granule
      release.

PMID- 17525300
TI  - Chemistry. Resolving an elusive structure.

PMID- 17525301
TI  - The structure of ferrihydrite, a nanocrystalline material.
AB  - Despite the ubiquity of ferrihydrite in natural sediments and its importance as
      an industrial sorbent, the nanocrystallinity of this iron oxyhydroxide has
      hampered accurate structure determination by traditional methods that rely on
      long-range order. We uncovered the atomic arrangement by real-space modeling of
      the pair distribution function (PDF) derived from direct Fourier transformation
      of the total x-ray scattering. The PDF for ferrihydrite synthesized with the use
      of different routes is consistent with a single phase (hexagonal space group
      P6(3)mc; a = approximately 5.95 angstroms, c = approximately 9.06 angstroms). In
      its ideal form, this structure contains 20% tetrahedrally and 80% octahedrally
      coordinated iron and has a basic structural motif closely related to the Baker
      Figgis delta-Keggin cluster. Real-space fitting indicates structural relaxation
      with decreasing particle size and also suggests that second-order effects such as
      internal strain, stacking faults, and particle shape contribute to the PDFs.

PMID- 17525302
TI  - Engineering complex dynamical structures: sequential patterns and
      desynchronization.
AB  - We used phase models to describe and tune complex dynamic structures to desired
      states; weak, nondestructive signals are used to alter interactions among
      nonlinear rhythmic elements. Experiments on electrochemical reactions on
      electrode arrays were used to demonstrate the power of mild model-engineered
      feedback to achieve a desired response. Applications are made to the generation
      of sequentially visited dynamic cluster patterns similar to reproducible
      sequences seen in biological systems and to the design of a nonlinear
      antipacemaker for the destruction of pathological synchronization of a population
      of interacting oscillators.

PMID- 17525303
TI  - Evolution and development of inflorescence architectures.
AB  - To understand the constraints on biological diversity, we analyzed how selection
      and development interact to control the evolution of inflorescences, the
      branching structures that bear flowers. We show that a single developmental model
      accounts for the restricted range of inflorescence types observed in nature and
      that this model is supported by molecular genetic studies. The model predicts
      associations between inflorescence architecture, climate, and life history, which
      we validated empirically. Paths, or evolutionary wormholes, link different
      architectures in a multidimensional fitness space, but the rate of evolution
      along these paths is constrained by genetic and environmental factors, which
      explains why some evolutionary transitions are rare between closely related plant
      taxa.

PMID- 17525304
TI  - Genetic properties influencing the evolvability of gene expression.
AB  - Identifying the properties of gene networks that influence their evolution is a
      fundamental research goal. However, modes of evolution cannot be inferred solely
      from the distribution of natural variation, because selection interacts with
      demography and mutation rates to shape polymorphism and divergence. We estimated
      the effects of naturally occurring mutations on gene expression while minimizing
      the effect of natural selection. We demonstrate that sensitivity of gene
      expression to mutations increases with both increasing trans-mutational target
      size and the presence of a TATA box. Genes with greater sensitivity to mutations
      are also more sensitive to systematic environmental perturbations and stochastic
      noise. These results provide a mechanistic basis for gene expression evolvability
      that can serve as a foundation for realistic models of regulatory evolution.

PMID- 17525305
TI  - New life for systematics.

PMID- 17525306
TI  - Avian influenza. Indonesia earns flu accord at World Health Assembly.

PMID- 17525308
TI  - Geochemistry. Isotopes suggest solar system formed in a rough neighborhood.

PMID- 17525307
TI  - Infectious disease. Resurgence of yellow fever in Africa prompts a counterattack.

PMID- 17525309
TI  - U.S politics. Nobelist eyes Minnesota Senate seat.

PMID- 17525310
TI  - Nonproliferation. Gloomier prospects for Indo-U.S. nuclear pact.

PMID- 17525311
TI  - Genetics. Working the (gene count) numbers: finally, a firm answer?

PMID- 17525312
TI  - Agbiotech. A growing threat down on the farm.

PMID- 17525313
TI  - Agbiotech. Glyphosate--the conservationist's friend?

PMID- 17525314
TI  - Antonio Giordano profile. 'Dr. Hustle' sells his dream for Italian medical
      research.

PMID- 17525315
TI  - DNA sequencing. A new window on how genomes work.

PMID- 17525316
TI  - Lessons from science communication training.

PMID- 17525317
TI  - Establishing rights over the Arctic Ocean.

PMID- 17525318
TI  - The march of HIV vaccines.

PMID- 17525319
TI  - Comment on "Dispersal limitations matter for microbial morphospecies".
AB  - Telford et al. (Brevia, 19 May 2006, p. 1015) reported that freshwater diatoms
      exhibit regional-scale richness-pH relationships that depend substantially on
      regional habitat availability. On this basis, the authors argued that, despite
      their microscopic size, diatoms are not ubiquitously dispersed. Here, I describe
      my demonstration that their primary evidence against the ubiquitous dispersal
      hypothesis is spurious.

PMID- 17525321
TI  - Applied physics. One electron makes current flow.

PMID- 17525320
TI  - Mathematics. Cognitive supports for analogies in the mathematics classroom.

PMID- 17525322
TI  - Chemistry. The direct approach.

PMID- 17525323
TI  - Astronomy. Dark matter in galactic collisional debris.

PMID- 17525324
TI  - Materials science. Hydrogel cell cultures.

PMID- 17525325
TI  - Geology. Assessing landslide hazards.

PMID- 17525326
TI  - Cell signaling. A touching response to damage.

PMID- 17525328
TI  - Single-molecule experiments in vitro and in silico.
AB  - Single-molecule force experiments in vitro enable the characterization of the
      mechanical response of biological matter at the nanometer scale. However, they do
      not reveal the molecular mechanisms underlying mechanical function. These can
      only be readily studied through molecular dynamics simulations of atomic
      structural models: "in silico" (by computer analysis) single-molecule
      experiments. Steered molecular dynamics simulations, in which external forces are
      used to explore the response and function of macromolecules, have become a
      powerful tool complementing and guiding in vitro single-molecule experiments. The
      insights provided by in silico experiments are illustrated here through a review
      of recent research in three areas of protein mechanics: elasticity of the muscle
      protein titin and the extracellular matrix protein fibronectin; linker-mediated
      elasticity of the cytoskeleton protein spectrin; and elasticity of ankyrin
      repeats, a protein module found ubiquitously in cells but with an as-yet unclear
      function.

PMID- 17525329
TI  - Forces and bond dynamics in cell adhesion.
AB  - Adhesion of a biological cell to another cell or the extracellular matrix
      involves complex couplings between cell biochemistry, structural mechanics, and
      surface bonding. The interactions are dynamic and act through association and
      dissociation of bonds between very large molecules at rates that change
      considerably under stress. Combining molecular cell biology with single-molecule
      force spectroscopy provides a powerful tool for exploring the complexity of cell
      adhesion, that is, how cell signaling processes strengthen adhesion bonds and how
      forces applied to cell-surface bonds act on intracellular sites to catalyze
      chemical processes or switch molecular interactions on and off. Probing adhesion
      receptors on strategically engineered cells with force during functional
      stimulation can reveal key nodes of communication between the mechanical and
      chemical circuitry of a cell.

PMID- 17525330
TI  - Far-field optical nanoscopy.
AB  - In 1873, Ernst Abbe discovered what was to become a well-known paradigm: the
      inability of a lens-based optical microscope to discern details that are closer
      together than half of the wavelength of light. However, for its most popular
      imaging mode, fluorescence microscopy, the diffraction barrier is crumbling.
      Here, I discuss the physical concepts that have pushed fluorescence microscopy to
      the nanoscale, once the prerogative of electron and scanning probe microscopes.
      Initial applications indicate that emergent far-field optical nanoscopy will have
      a strong impact in the life sciences and in other areas benefiting from nanoscale
      visualization.

PMID- 17525331
TI  - Visual language discrimination in infancy.
AB  - This study shows that 4- and 6-month-old infants can discriminate languages
      (English from French) just from viewing silently presented articulations. By the
      age of 8 months, only bilingual (French-English) infants succeed at this task.
      These findings reveal a surprisingly early preparedness for visual language
      discrimination and highlight infants' selectivity for retaining only necessary
      perceptual sensitivities.

PMID- 17525332
TI  - ATM and ATR substrate analysis reveals extensive protein networks responsive to
      DNA damage.
AB  - Cellular responses to DNA damage are mediated by a number of protein kinases,
      including ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related). The
      outlines of the signal transduction portion of this pathway are known, but little
      is known about the physiological scope of the DNA damage response (DDR). We
      performed a large-scale proteomic analysis of proteins phosphorylated in response
      to DNA damage on consensus sites recognized by ATM and ATR and identified more
      than 900 regulated phosphorylation sites encompassing over 700 proteins.
      Functional analysis of a subset of this data set indicated that this list is
      highly enriched for proteins involved in the DDR. This set of proteins is highly
      interconnected, and we identified a large number of protein modules and networks
      not previously linked to the DDR. This database paints a much broader landscape
      for the DDR than was previously appreciated and opens new avenues of
      investigation into the responses to DNA damage in mammals.

PMID- 17525333
TI  - An on-demand coherent single-electron source.
AB  - We report on the electron analog of the single-photon gun. On-demand single
      electron injection in a quantum conductor was obtained using a quantum dot
      connected to the conductor via a tunnel barrier. Electron emission was triggered
      by the application of a potential step that compensated for the dot-charging
      energy. Depending on the barrier transparency, the quantum emission time ranged
      from 0.1 to 10 nanoseconds. The single-electron source should prove useful for
      the use of quantum bits in ballistic conductors. Additionally, periodic sequences
      of single-electron emission and absorption generate a quantized alternating
      current.

PMID- 17525334
TI  - The catalytic cross-coupling of unactivated arenes.
AB  - The industrially important coupling of aromatic compounds has generally required
      differential prefunctionalization of the arene coupling partners with a halide
      and an electropositive group. Here we report that palladium, in conjunction with
      a copper oxidant, can catalyze the cross-coupling of N-acetylindoles and benzenes
      in high yield and high regioselectivity across a range of indoles without
      recourse to activating groups. These reactions are completely selective for arene
      cross-coupling, with no products arising from indole or benzene homo-coupling
      detected by spectroscopic analysis. This efficient reactivity should be useful in
      the design of other oxidative arene cross-couplings as well.

PMID- 17525335
TI  - Chondrite barium, neodymium, and samarium isotopic heterogeneity and early Earth
      differentiation.
AB  - Isotopic variability in barium, neodymium, and samarium in carbonaceous
      chondrites reflects the distinct stellar nucleosynthetic contributions to the
      early solar system. We used 148Nd/144Nd to correct for the observed s-process
      deficiency, which produced a chondrite 146Sm-142Nd isochron consistent with
      previous estimates of the initial solar system abundance of 146Sm and a
      142Nd/144Nd at average chondrite Sm/Nd ratio that is lower than that measured in
      terrestrial rocks by 21 +/- 3 parts per million. This result strengthens the
      conclusion that the deficiency in 142Nd in chondrites relative to terrestrial
      rocks reflects 146Sm decayand earlyplanetary differentiation processes.

PMID- 17525336
TI  - Evidence for a late supernova injection of 60Fe into the protoplanetary disk.
AB  - High-precision 60Fe-60Ni isotope data show that most meteorites originating from
      differentiated planetesimals that accreted within 1 million years of the solar
      system's formation have 60Ni/58Ni ratios that are approximately 25 parts per
      million lower than samples from Earth, Mars, and chondrite parent bodies. This
      difference indicates that the oldest solar system planetesimals formed in the
      absence of 60Fe. Evidence for live 60Fe in younger objects suggests that 60Fe was
      injected into the protoplanetary disk approximately 1 million years after solar
      system formation, when 26Al was already homogeneously distributed. Decoupling the
      first appearance of 26Al and 60Fe constrains the environment where the Sun's
      formation could have taken place, indicating that it occurred in a dense stellar
      cluster in association with numerous massive stars.

PMID- 17525337
TI  - Dicamba resistance: enlarging and preserving biotechnology-based weed management
      strategies.
AB  - The advent of biotechnology-derived, herbicide-resistant crops has revolutionized
      farming practices in many countries. Facile, highly effective, environmentally
      sound, and profitable weed control methods have been rapidly adopted by crop
      producers who value the benefits associated with biotechnology-derived weed
      management traits. But a rapid rise in the populations of several troublesome
      weeds that are tolerant or resistant to herbicides currently used in conjunction
      with herbicide-resistant crops may signify that the useful lifetime of these
      economically important weed management traits will be cut short. We describe the
      development of soybean and other broadleaf plant species resistant to dicamba, a
      widely used, inexpensive, and environmentally safe herbicide. The dicamba
      resistance technology will augment current herbicide resistance technologies and
      extend their effective lifetime. Attributes of both nuclear- and chloroplast
      encoded dicamba resistance genes that affect the potency and expected durability
      of the herbicide resistance trait are examined.

PMID- 17525338
TI  - A manganese(IV)/iron(III) cofactor in Chlamydia trachomatis ribonucleotide
      reductase.
AB  - In a conventional class I ribonucleotide reductase (RNR), a diiron(II/II)
      cofactor in the R2 subunit reacts with oxygen to produce a diiron(III/IV)
      intermediate, which generates a stable tyrosyl radical (Y*). The Y* reversibly
      oxidizes a cysteine residue in the R1 subunit to a cysteinyl radical (C*), which
      abstracts the 3'-hydrogen of the substrate to initiate its reduction. The RNR
      from Chlamydia trachomatis lacks the Y*, and it had been proposed that the
      diiron(III/IV) complex in R2 directly generates the C* in R1. By enzyme activity
      measurements and spectroscopic methods, we show that this RNR actually uses a
      previously unknown stable manganese(IV)/iron(III) cofactor for radical
      initiation.

PMID- 17525339
TI  - Probing transcription factor dynamics at the single-molecule level in a living
      cell.
AB  - Transcription factors regulate gene expression through their binding to DNA. In a
      living Escherichia coli cell, we directly observed specific binding of a lac
      repressor, labeled with a fluorescent protein, to a chromosomal lac operator.
      Using single-molecule detection techniques, we measured the kinetics of binding
      and dissociation of the repressor in response to metabolic signals. Furthermore,
      we characterized the nonspecific binding to DNA, one-dimensional (1D) diffusion
      along DNA segments, and 3D translocation among segments through cytoplasm at the
      single-molecule level. In searching for the operator, a lac repressor spends
      approximately 90% of time nonspecifically bound to and diffusing along DNA with a
      residence time of <5 milliseconds. The methods and findings can be generalized to
      other nucleic acid binding proteins.

PMID- 17525340
TI  - Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage
      response.
AB  - The BRCT repeats of the breast and ovarian cancer predisposition protein BRCA1
      are essential for tumor suppression. Phosphopeptide affinity proteomic analysis
      identified a protein, Abraxas, that directly binds the BRCA1 BRCT repeats through
      a phospho-Ser-X-X-Phe motif. Abraxas binds BRCA1 to the mutual exclusion of BACH1
      (BRCA1-associated C-terminal helicase) and CtIP (CtBP-interacting protein),
      forming a third type of BRCA1 complex. Abraxas recruits the ubiquitin-interacting
      motif (UIM)-containing protein RAP80 to BRCA1. Both Abraxas and RAP80 were
      required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair.
      RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in
      response to ionizing radiation, and the UIM domains alone were capable of foci
      formation. The RAP80-Abraxas complex may help recruit BRCA1 to DNA damage sites
      in part through recognition of ubiquitinated proteins.

PMID- 17525341
TI  - RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites.
AB  - Mutations affecting the BRCT domains of the breast cancer-associated tumor
      suppressor BRCA1 disrupt the recruitment of this protein to DNA double-strand
      breaks (DSBs). The molecular structures at DSBs recognized by BRCA1 are presently
      unknown. We report the interaction of the BRCA1 BRCT domain with RAP80, a
      ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1
      (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating
      enzyme (DUB) BRCC36 to MDC1-gammaH2AX-dependent lysine(6)- and lysine(63)-linked
      ubiquitin polymers at DSBs. These events are required for cell cycle checkpoint
      and repair responses to ionizing radiation, implicating ubiquitin chain
      recognition and turnover in the BRCA1-mediated repair of DSBs.

PMID- 17525342
TI  - Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response.
AB  - Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with
      an increased risk of breast and ovarian cancers. BRCA1 participates in the
      cellular DNA damage response. We report the identification of receptor-associated
      protein 80 (RAP80) as a BRCA1-interacting protein in humans. RAP80 contains a
      tandem ubiquitin-interacting motif domain, which is required for its binding with
      ubiquitin in vitro and its damage-induced foci formation in vivo. Moreover, RAP80
      specifically recruits BRCA1 to DNA damage sites and functions with BRCA1 in G2/M
      checkpoint control. Together, these results suggest the existence of a
      ubiquitination-dependent signaling pathway involved in the DNA damage response.

PMID- 17525343
TI  - Myosin V walks by lever action and Brownian motion.
AB  - Myosin V is a molecular motor that moves cargo along actin filaments. Its two
      heads, each attached to a long and relatively stiff neck, move alternately
      forward in a "hand-over-hand" fashion. To observe under a microscope how the
      necks move, we attached a micrometer-sized rod to one of the necks. The leading
      neck swings unidirectionally forward, whereas the trailing neck, once lifted,
      undergoes extensive Brownian rotation in all directions before landing on a site
      ahead of the leading head. The neck-neck joint is essentially free, and the neck
      motion supports a mechanism where the active swing of the leading neck biases the
      random motion of the lifted head to let it eventually land on a forward site.

PMID- 17525344
TI  - Hardwiring the brain: endocannabinoids shape neuronal connectivity.
AB  - The roles of endocannabinoid signaling during central nervous system development
      are unknown. We report that CB(1) cannabinoid receptors (CB(1)Rs) are enriched in
      the axonal growth cones of gamma-aminobutyric acid-containing (GABAergic)
      interneurons in the rodent cortex during late gestation. Endocannabinoids trigger
      CB(1)R internalization and elimination from filopodia and induce chemorepulsion
      and collapse of axonal growth cones of these GABAergic interneurons by activating
      RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis
      spinal neurons. These findings, together with the impaired target selection of
      cortical GABAergic interneurons lacking CB(1)Rs, identify endocannabinoids as
      axon guidance cues and demonstrate that endocannabinoid signaling regulates
      synaptogenesis and target selection in vivo.

PMID- 17525345
TI  - Oral health is global health.

PMID- 17525346
TI  - Connectedness.

PMID- 17525347
TI  - The emergence of "nanospheres" as basic structural components adopted by
      amelogenin.

PMID- 17525348
TI  - Orofacial pain in cancer: part I--mechanisms.
AB  - The mechanisms involved, and possible treatment targets, in orofacial pain due to
      cancer are poorly understood. The aim of the first of this two-part series is to
      review the involved pathophysiological mechanisms and explore their possible
      roles in the orofacial region. However, there is a lack of relevant research in
      the trigeminal region, and we have therefore applied data accumulated from
      experiments on cancer pain mechanisms in rodent spinal models. In the second
      part, we review the clinical presentation of cancer-associated orofacial pain at
      various stages: initial diagnosis, during therapy (chemo-, radiotherapy,
      surgery), and in the post-therapy period. In the present article, we provide a
      brief outline of trigeminal functional neuro-anatomy and pain-modulatory
      pathways. Tissue destruction by invasive tumors (or metastases) induces
      inflammation and nerve damage, with attendant acute pain. In some cases, chronic
      pain, involving inflammatory and neuropathic mechanisms, may ensue. Distant,
      painful effects of tumors include paraneoplastic neuropathic syndromes and
      effects secondary to the release of factors by the tumor (growth factors,
      cytokines, and enzymes). Additionally, pain is frequent in cancer management
      protocols (surgery, chemotherapy, and radiotherapy). Understanding the mechanisms
      involved in cancer-related orofacial pain will enhance patient management.

PMID- 17525349
TI  - Orofacial pain in cancer: part II--clinical perspectives and management.
AB  - Cancer-associated pain is extremely common and is associated with significant
      physical and psychological suffering. Unfortunately, pain associated with cancer
      or its treatment is frequently under-treated, probably due to several factors,
      including phobia of opioids, under-reporting by patients, and under-diagnosis by
      healthcare workers. The most common etiology of cancer pain is local tumor
      invasion (primary or metastatic), involving inflammatory and neuropathic
      mechanisms; these have been reviewed in Part I. As malignant disease advances,
      pain usually becomes more frequent and more intense. Additional expressions of
      orofacial cancer pain include distant tumor effects, involving paraneoplastic
      mechanisms. Pain secondary to cancer therapy varies with the treatment modalities
      used: Chemo-radiotherapy protocols are typically associated with painful
      mucositis and neurotoxicity. Surgical therapies often result in nerve and tissue
      damage, leading, in the long term, to myofascial and neuropathic pain syndromes.
      In the present article, we review the clinical presentation of cancer-associated
      orofacial pain at various stages: initial diagnosis, during therapy (chemo-,
      radiotherapy, surgery), and in the post-therapy period. As a presenting symptom
      of orofacial cancer, pain is often of low intensity and diagnostically
      unreliable. Diagnosis, treatment, and prevention of pain in cancer require
      knowledge of the presenting characteristics, factors, and mechanisms involved.

PMID- 17525350
TI  - Resin elasticity and the strengthening of all-ceramic restorations.
AB  - Resin luting of all-ceramic restorations results in increased performance;
      however, the strengthening mechanism and the role of the mechanical properties of
      the resin are not fully understood. The hypothesis tested is that ceramic
      strength enhancement is dependent on the elastic modulus of the resin. Three
      point flexural moduli of a flowable, luting, and hybrid composite resin were
      characterized. Two hundred forty porcelain discs were air-abraded. One group
      acted as a control, and 3 additional groups were coated with 120 +/- 20 microm of
      each resin prior to bi-axial flexure testing. All resins significantly increased
      in mean strength, and the associated strength increase was related to the elastic
      modulus of the resin (R(2) = 0.9885), so the hypothesis was accepted. The
      combination of Poisson constraint and the creation of a resin-inter-penetrating
      layer sensitive to the elastic modulus of the resin may provide an explanation of
      the strengthening mechanism.

PMID- 17525351
TI  - Tubular occlusion optimizes bonding of hydrophobic resins to dentin.
AB  - Although hydrophobic resins may be bonded to acid-etched dentin with an ethanol
      wet-bonding technique, the protocol is sensitive to moisture contamination when
      bonding is performed in deep dentin. This study tested the hypothesis that the
      use of oxalate or poly(glutamic) acid-modified, diluted ceramicrete (PADC) for
      dentinal tubule occlusion prevents fluid contamination and improves the bonding
      of an experimental hydrophobic adhesive to acid-etched, ethanol-dehydrated
      dentin. Mid-coronal and deep acid-etched moist dentin pre-treated with oxalate or
      PADC was dehydrated by ethanol wet-bonding and infiltrated with the experimental
      three-step etch-and-rinse hydrophobic adhesive under simulated pulpal pressure.
      Tensile bond strengths to deep dentin without pre-treatment were severely
      compromised. Conversely, oxalate and PADC pre-treatments reduced dentin
      permeability, prevented water contamination, and improved bond strengths. Minimal
      nanoleakage was identified within hybrid layers created in the oxalate- and PADC
      pre-treated deep dentin. The use of tubular occluding agents optimized bonding of
      hydrophobic resins to dentin.

PMID- 17525352
TI  - In vivo preservation of the hybrid layer by chlorhexidine.
AB  - Host-derived proteases have been reported to degrade the collagen matrix of
      incompletely-resin-infiltrated dentin. This study tested the hypothesis that
      interfacial degradation of resin-dentin bonds may be prevented or delayed by the
      application of chlorhexidine (CHX), a matrix metalloproteinase inhibitor, to
      dentin after phosphoric acid-etching. Contralateral pairs of resin-bonded Class I
      restorations in non-carious third molars were kept under intra-oral function for
      14 months. Preservation of resin-dentin bonds was assessed by microtensile bond
      strength tests and TEM examination. In vivo bond strength remained stable in the
      CHX-treated specimens, while bond strength decreased significantly in control
      teeth. Resin-infiltrated dentin in CHX-treated specimens exhibited normal
      structural integrity of the collagen network. Conversely, progressive
      disintegration of the fibrillar network was identified in control specimens. Auto
      degradation of collagen matrices can occur in resin-infiltrated dentin, but may
      be prevented by the application of a synthetic protease inhibitor, such as
      chlorhexidine.

PMID- 17525353
TI  - Effects of EDTA on the hydration mechanism of mineral trioxide aggregate.
AB  - Ethylenediaminetetraacetic acid (EDTA) is commonly used during the preparation of
      obstructed root canals that face a high risk of root perforation. Such
      perforations may be repaired with mineral trioxide aggregate (MTA). Due to EDTA's
      ability to chelate calcium ions, we hypothesized that EDTA may disrupt the
      hydration of MTA. Using scanning electron microscopy and energy-dispersive x-ray
      spectroscopy, we found that MTA specimens stored in an EDTA solution had no
      crystalline structure and a Ca/Si molar ratio considerably lower than those
      obtained for specimens stored in distilled water and normal saline. Poor cell
      adhesion in EDTA-treated MTA was also noted. X-ray diffraction indicated that the
      peak corresponding to portlandite, which is normally present in hydrated MTA, was
      not shown in the EDTA group. The microhardness of EDTA-treated specimens was also
      significantly reduced (p < 0.0001). These findings suggest that EDTA interferes
      with the hydration of MTA, resulting in decreased hardness and poor
      biocompatibility.

PMID- 17525354
TI  - Effect of load deflection on corrosion behavior of NiTi wire.
AB  - For dental orthodontic applications, NiTi wires are used under bending conditions
      in the oral environment for a long period. The purpose of this study was to
      investigate the effect of bending stress on the corrosion of NiTi wires using
      potentiodynamic and potentiostatic tests in artificial saliva. The results
      indicated that bending stress induces a higher corrosion rate of NiTi wires in
      passive regions. It is suggested that the passive oxide film of specimens would
      be damaged under bending conditions. Auger electron spectroscopic analysis showed
      a lower thickness of passive films on stressed NiTi wires compared with
      unstressed specimens in the passive region. By scanning electron microscopy,
      localized corrosion was observed on stressed Sentalloy specimens after a
      potentiodynamic test at pH 2. In conclusion, this study indicated that bending
      stress changed the corrosion properties and surface characteristics of NiTi wires
      in a simulated intra-oral environment.

PMID- 17525355
TI  - Genetic changes in sporadic keratocystic odontogenic tumors (odontogenic
      keratocysts).
AB  - Little is known about the genetic background of keratocystic odontogenic tumors
      (KCOT, odontogenic keratocysts). Our aim was to characterize genomic aberrations
      in sporadic KCOT using cDNA-expression arrays and array-comparative genomic
      hybridization. For cDNA-expression arrays, 10 KCOT specimens and 20 fetal tooth
      germs were studied. Quantitative real-time reverse-transcription/polymerase chain
      reaction and immunohistochemical studies were also undertaken. Several genes were
      over-expressed in 12q13, including cytokeratin 6B (KRT6B) ( approximately 10
      fold), epidermal growth factor receptor ERBB3 (approximately 4.7-fold), and
      glioma-associated oncogene homologue 1 (GLI1) (approximately 5- to 12-fold). One
      amplicon (approximately 0.7 Mega base pairs [Mbp]), covering several genes
      involved in the regulation of cell growth, was found in 12q13.2. Deletions were
      found in 3q13.1, 5p14.3, and 7q31.3, including the cell-adhesion-related gene
      cadherin 18 (CDH18) and leukocyte cell adhesion molecule (ALCAM, MEMD). Over
      expressed and amplified genes in 12q13, also reported in several other tumors and
      cell lines, may contribute to the persistent growth characteristics of KCOT.

PMID- 17525356
TI  - NGF up-regulates TRPA1: implications for orofacial pain.
AB  - The transient receptor potential ankyrin repeat 1 (TRPA1) channel is believed to
      be involved in many forms of acute and chronic hyperalgesia. Nerve Growth Factor
      (NGF) regulates chronic inflammatory hyperalgesia by controlling gene expression
      in sensory neurons, including genes involved in inflammatory hyperalgesia in the
      dental pulp. We hypothesized that NGF increases functional activities of the
      TRPA1 channel in trigeminal ganglion neurons. Here, we show that NGF induced a
      concentration- and time-dependent up-regulation of TRPA1 mRNA in trigeminal
      ganglia neurons, as detected by real-time RT-PCR and in situ hybridization. In
      addition, NGF evoked a time-dependent increase of mustard oil (MO)-evoked TRPA1
      activation in trigeminal ganglia neurons. Collectively, these findings
      demonstrate that NGF participates in the functional up-regulation of TRPA1 in
      trigeminal ganglia neurons. These enhanced activities of TRPA1 could play an
      important role in the development of hyperalgesia following nerve injury and
      inflammation in the orofacial region.

PMID- 17525357
TI  - Nuclear factor kappaB p65 phosphorylation in orthodontic tooth movement.
AB  - Osteoclasts play a vital role in orthodontic tooth movement. Transactivation of
      nuclear factor kappaB (NFkappaB) by phosphorylation of the p65 component of
      NFkappaB at amino acid 536 (p65*(536)) plays a role in osteoclast differentiation
      stimulated by receptor activator of nuclear factor kappaB-ligand (RANK-L). We
      hypothesized that this transactivation pathway might be involved in the responses
      of alveolar bone cells during orthodontic tooth movement. We detected sharp
      increases in the levels of p65*(536) 3 and 12 hrs after the application of
      orthodontic stimuli in rats. In cell culture, osteoclast-like cells displayed no
      changes in p65*(536) in response to RANK-L, but levels rapidly increased after
      the cells were mechanically scraped. We conclude that p65*(536) is produced
      rapidly in response to orthodontic stimuli and mechanical insults, and may be
      important in bone remodeling associated with orthodontic tooth movement.

PMID- 17525358
TI  - IL-10 gene transfer attenuates P. gingivalis-induced inflammation.
AB  - IL-10 is an anti-inflammatory cytokine secreted by stimulated Th2 lymphocytes
      that can down-regulate inflammatory responses to bacterial challenge. We
      hypothesized that local delivery of IL-10 using gene-transfer will down-regulate
      inflammatory responses. We examined the effect of IL-10 plasmid injection on the
      local cytokine response. Two weeks after the implantation of chambers, either IL
      10 plasmid or vector was injected into the mice. Four days later, they were
      challenged with an intra-chamber injection of P. gingivalis. The intra-chamber
      levels of IL-10, IFNgamma, TNFalpha, and IL-1beta were evaluated after 2 and 24
      hrs. The results showed that local IL-10 gene delivery elevated the levels of IL
      10 at both time periods. It attenuated the levels of IFNgamma (656 +/- 154 to 218
      +/- 144 pg/mL) and TNFalpha (23 +/- 2.0 to 12.5 +/- 2.9 ng/mL) at 2 hrs, and of
      IL-1beta (21.5 +/- 5.7 to 12.4 +/- 3.0 ng/mL) at 24 hrs. The results suggest the
      possibility of modulating the local inflammatory response to P. gingivalis by
      direct IL-10 gene transfer.

PMID- 17525359
TI  - Responses of the human submandibular artery to ACh and VIP.
AB  - Endothelial vasodilatory substances may play a central role in the local
      regulation of vascular tone. We hypothesized that these substances can mediate
      endothelium-dependent vasodilatory responses to acetylcholine (ACh) and
      vasoactive intestinal peptide (VIP) in the human submandibular artery. We
      evaluated the contributions of endothelial vasodilatory substances to vessel
      relaxation in response to ACh and VIP, using different inhibitors of endothelial
      vasodilation, the nitric oxide synthase inhibitor, the cyclo-oxygenase inhibitor,
      indomethacin, the potassium channel blocker, and 4-aminopyridine. ACh and VIP
      caused an endothelium- and concentration-dependent relaxation in this artery. ACh
      relaxation was completely blocked after the concomitant addition of N(G)-nitro-L
      arginine and indomethacin. The vasorelaxant effect of ACh was not influenced by 4
      aminopyridine. VIP relaxation was almost completely abolished by 4-aminopyridine,
      and was partly inhibited by N(G)-nitro-L-arginine, but was not affected by
      indomethacin. Thus, in the human submandibular artery, ACh and VIP produced
      endothelium-dependent vasodilation with different underlying mechanisms: release
      of nitric oxide (NO) and cyclo-oxygenase products for ACh, and release of NO and
      endothelium-derived hyperpolarizing factor for VIP.

PMID- 17525360
TI  - Effect of facial sensory re-training on sensory thresholds.
AB  - Nearly 100% of patients experience trauma to the trigeminal nerve during
      orthognathic surgery, impairing sensation and sensory function on the face. In a
      recent randomized clinical trial, people who performed sensory re-training
      exercises reported less difficulty related to residual numbness and decreased lip
      sensitivity than those who performed standard opening exercises only. We
      hypothesized that re-training reduces the impaired performance on neurosensory
      tests of tactile function that is commonly observed post-surgically. We analyzed
      thresholds for contact detection, two-point discrimination, and two-point
      perception, obtained during the clinical trial before and at 1, 3, and 6 months
      after surgery, to assess tactile detection and discriminative sensitivities, and
      subjective interpretation of tactile stimulation, respectively. Post-surgery, the
      retrained persons exhibited less impairment, on average, than non-retrained
      persons only in two-point perception (P < 0.025), suggesting that retrained
      persons experienced or interpreted the tactile stimuli differently than did non
      retrained persons.

PMID- 17525361
TI  - Cardiovascular actions of insulin.
AB  - Insulin has important vascular actions to stimulate production of nitric oxide
      from endothelium. This leads to capillary recruitment, vasodilation, increased
      blood flow, and subsequent augmentation of glucose disposal in classical insulin
      target tissues (e.g., skeletal muscle). Phosphatidylinositol 3-kinase-dependent
      insulin-signaling pathways regulating endothelial production of nitric oxide
      share striking parallels with metabolic insulin-signaling pathways. Distinct MAPK
      dependent insulin-signaling pathways (largely unrelated to metabolic actions of
      insulin) regulate secretion of the vasoconstrictor endothelin-1 from endothelium.
      These and other cardiovascular actions of insulin contribute to coupling
      metabolic and hemodynamic homeostasis under healthy conditions. Cardiovascular
      diseases are the leading cause of morbidity and mortality in insulin-resistant
      individuals. Insulin resistance is typically defined as decreased sensitivity
      and/or responsiveness to metabolic actions of insulin. This cardinal feature of
      diabetes, obesity, and dyslipidemia is also a prominent component of
      hypertension, coronary heart disease, and atherosclerosis that are all
      characterized by endothelial dysfunction. Conversely, endothelial dysfunction is
      often present in metabolic diseases. Insulin resistance is characterized by
      pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling
      that in vascular endothelium contributes to a reciprocal relationship between
      insulin resistance and endothelial dysfunction. The clinical relevance of this
      coupling is highlighted by the findings that specific therapeutic interventions
      targeting insulin resistance often also ameliorate endothelial dysfunction (and
      vice versa). In this review, we discuss molecular mechanisms underlying
      cardiovascular actions of insulin, the reciprocal relationships between insulin
      resistance and endothelial dysfunction, and implications for developing
      beneficial therapeutic strategies that simultaneously target metabolic and
      cardiovascular diseases.

PMID- 17525362
TI  - Thrombotic thrombocytopenic purpura in humans and mice.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a disorder of blood coagulation that
      presents classically with the pentad of fever, thrombocytopenia, microangiopathic
      hemolytic anemia, renal dysfunction and mental status changes. However, the
      clinical presentation can be quite variable making the diagnosis difficult in
      many cases. "Hyaline" microthrombi composed primarily of platelets and Von
      Willebrand Factor (VWF) are found in the small vessels of affected organs and
      represent the pathological hallmark of the disease. The accompanying tissue
      ischemia is thought to explain the clinical TTP signs and symptoms. Pathogenesis
      of TTP has been linked to dysfunction of ADAMTS13, a metalloprotease whose only
      known substrate is VWF. Interestingly, further investigation into the natural
      history of TTP has demonstrated that ADAMTS13 deficiency likely is necessary, but
      not sufficient for the development of this disease, suggesting that additional
      genetic and/or environmental factors are required for TTP pathogenesis. Recently,
      a mouse model of TTP was established that recapitulates many of the key clinical
      features of this disease, including the requirement for further genetic and
      environmental factors in addition to ADAMTS13 deficiency. Therefore, in addition
      to being useful for the direct study of disease pathophysiology in vivo, this
      mouse model may also play a key role in elucidating some of the important
      environmental and genetic contributors to disease pathogenesis. Here we will
      review TTP in humans, and then discuss recent information gained from the
      analysis of ADAMTS13-deficient mice.

PMID- 17525363
TI  - Effects of unfractionated heparin and glycoprotein IIb/IIIa antagonists versus
      bivalirdin on myeloperoxidase release from neutrophils.
AB  - OBJECTIVES The objective of this study was to determine whether adjunctive
      therapy during percutaneous coronary intervention (PCI) affects markers of
      systemic inflammation or platelet activation. Despite different mechanisms of
      action, direct-thrombin inhibition with bivalirudin during PCI provided similar
      protection from periprocedural and chronic ischemic complications as compared
      with unfractionated heparin (UFH) plus planned use of GPIIb/IIIa antagonists in
      the REPLACE-2 and ACUITY trials. METHODS AND RESULTS: Patients undergoing
      nonurgent PCI of a native coronary artery were randomized to receive adjunctive
      therapy with bivalirudin or UFH+eptifibatide. Interleukin (IL)-6 and C-reactive
      protein (CRP) transiently increased in both groups after PCI. In the
      UFH+eptifibatide, but not the bivalirudin group, myeloperoxidase (MPO) levels
      were elevated 2.3-fold above baseline (P=0.004) immediately after PCI. In an in
      vitro assay, heparin and to a lesser extent enoxaparin, but not bivalirudin or
      eptifibatide, stimulated MPO release from and binding to neutrophils and
      neutrophil activation. A mouse model of endoluminal femoral artery denudation was
      used to investigate further the importance of MPO in the context of arterial
      injury. CONCLUSIONS: Adjuvant therapy during PCI may have undesired effects on
      neutrophil activation, MPO release, and systemic inflammation.

PMID- 17525364
TI  - Increased inhibition of inward rectifier K+ channels by angiotensin II in small
      diameter coronary artery of isoproterenol-induced hypertrophied model.
AB  - OBJECTIVE: We investigated the effects of angiotensin II (Ang II) on inward
      rectifier K+ (Kir) channels in small-diameter coronary arterial smooth muscle
      cells (SCASMCs) of control and isoproterenol (Iso)-induced hypertrophied rabbits.
      METHODS AND RESULTS: Kir current amplitude and Kir channel protein expression
      were definitely lower in the Iso-induced hypertrophied model than in the control.
      In a pressurized arterial experiment, 15 mmol/L K+-induced vasodilation was
      greater in the control arteries than in the arteries of Iso-induced hypertrophied
      model. Ang II reduced the Kir current in a concentration-dependent manner, and
      this inhibition was greater in SCASMCs from Iso-induced hypertrophied model than
      from control. Although, there was no difference in the expression of Ang II type
      2 (AT2) receptor between SCASMCs of control and Iso-induced hypertrophied model,
      the expression of Ang II type 1 (AT1) receptor and phosphorylated PKC alpha were
      greater in SCASMCs of Iso-induced hypertrophied model than of control.
      CONCLUSION: Ang II inhibits Kir channels more prominently in SCASMCs of Iso
      induced hypertrophied model owing to increases in the expression of AT1 receptor
      and the activation of PKC alpha. Our findings about the differential expression
      of Kir channels and different modulation of Kir channels by a vasoconstrictor
      (Ang II) in a hypertrophy model are important for better understanding the
      responsiveness of small-diameter arteries during hypertrophy.

PMID- 17525365
TI  - Vascular endothelial growth factor is induced by the inflammatory cytokines
      interleukin-6 and oncostatin m in human adipose tissue in vitro and in murine
      adipose tissue in vivo.
AB  - OBJECTIVES: It is believed that adipose tissue acts as an endocrine organ by
      producing inflammatory mediators and thereby contributes to the increased
      cardiovascular risk seen in obesity. A link between adipose tissue mass and
      angiogenesis has been suggested. Vascular endothelial growth factor (VEGF) seems
      to be implicated in this process. Members of the glycoprotein (gp)130 ligand
      family regulate VEGF expression in other cells. METHODS AND RESULTS: We used
      tissue explants as well as primary cultures of preadipocytes and adipocytes from
      human subcutaneous and visceral adipose tissue to investigate whether the gp130
      ligands oncostatin M (OSM), interleukin-6 (IL-6), leukemia inhibitory factor
      (LIF), and cardiotrophin-1 (CT-1) regulate VEGF expression in human adipose
      tissue. Human subcutaneous and visceral adipose tissue responded to treatment
      with IL-6 and OSM with a significant increase in VEGF production. Human
      preadipocytes were isolated from subcutaneous and visceral adipose tissue.
      Adipocyte-differentiation was induced by hormone-supplementation. All cell types
      responded to IL-6 and OSM with a robust increase in VEGF protein production and a
      similar increase in VEGF-specific mRNA. Furthermore, IL-1beta synergistically
      enhanced the effect of OSM on VEGF production. AG-490, a JAK/STAT inhibitor,
      abolished the OSM-dependent VEGF induction almost completely. In mice, IL-6 and
      OSM increased serum levels of VEGF and VEGF mRNA and vessel density in adipose
      tissue. CONCLUSION: We speculate that the inflammatory cytokines IL-6 and OSM
      might support angiogenesis during adipose tissue growth by upregulating VEGF.

PMID- 17525366
TI  - Calcium cycling protein density and functional importance to automaticity of
      isolated sinoatrial nodal cells are independent of cell size.
AB  - Spontaneous, localized, rhythmic ryanodine receptor (RyRs) Ca(2+) releases occur
      beneath the cell membrane during late diastolic depolarization in cardiac
      sinoatrial nodal cells (SANCs). These activate the Na(+)/Ca(2+) exchanger (NCX1)
      to generate inward current and membrane excitation that drives normal spontaneous
      beating. The morphological background for the proposed functional of RyR and NCX
      crosstalk, however, has not been demonstrated. Here we show that the average
      isolated SANC whole cell labeling density of RyRs and SERCA2 is similar to atrial
      and ventricle myocytes, and is similar among SANCs of all sizes. Labeling of NCX1
      is also similar among SANCs of all sizes and exceeds that in atrial and ventricle
      myocytes. Submembrane colocalization of NCX1 and cardiac RyR (cRyR) in all SANCs
      exceeds that in the other cell types. Further, the Cx43 negative primary
      pacemaker area of the intact rabbit sinoatrial node (SAN) exhibits robust
      positive labeling for cRyR, NCX1, and SERCA2. Functional studies in isolated
      SANCs show that neither the average action potential (AP) characteristics, nor
      those of intracellular Ca(2+) releases, nor the spontaneous cycle length vary
      with cell size. Chelation of intracellular [Ca(2+)], or disabling RyRs or NCX1,
      markedly attenuates or abolishes spontaneous SANC beating in all SANCs. Thus,
      there is dense labeling of SERCA2, RyRs, and NCX1 in small-sized SANCs, thought
      to reside within the SAN center, the site of impulse initiation. Because normal
      automaticity of these cells requires intact Ca(2+) cycling, interactions of
      SERCA, RyR2 and NCX molecules are implicated in the initiation of the SAN
      impulse.

PMID- 17525367
TI  - Downregulation of the hemoglobin scavenger receptor in individuals with diabetes
      and the Hp 2-2 genotype: implications for the response to intraplaque hemorrhage
      and plaque vulnerability.
AB  - In individuals with diabetes mellitus (DM), the haptoglobin (Hp) genotype is a
      major determinant of susceptibility to myocardial infarction. We have proposed
      that this is because of DM and Hp genotype-dependent differences in the response
      to intraplaque hemorrhage. The macrophage hemoglobin scavenging receptor CD163
      plays an essential role in the clearance of hemoglobin released from lysed red
      blood cells after intraplaque hemorrhage. We sought to test the hypothesis that
      expression of CD163 is DM and Hp genotype-dependent. CD163 was quantified in
      plaques by immunohistochemistry, on peripheral blood monocytes (PBMs) by FACS,
      and as soluble CD163 (sCD163) in plasma by ELISA. In DM plaques, despite an
      increase in macrophage infiltration, CD163 immunoreactivity was lower, resulting
      in a dramatic reduction in the percentage of macrophages expressing CD163 (27+/
      2% versus 70+/-2%, P=0.0001). In individuals with DM as compared with individuals
      without DM, the percentage of PBMs expressing CD163 was reduced (3.7+/-0.6%
      versus 7.1+/-0.9%, P<0.002) whereas soluble plasma CD163 was increased (2.6+/-1.1
      microg/mL versus 1.6+/-0.8 microg/mL, P<0.0005). Among DM individuals, the Hp 2-2
      genotype was associated with a decrease in the percentage of PBMs expressing
      CD163 (2.3+/-0.5% versus 5.6+/-1.3%, P=0.01) and an increase in plasma soluble
      CD163 (3.0+/-0.2 microg/mL versus 2.3+/-0.2 microg/mL, P=0.04). Taken together,
      these results demonstrate an impaired hemoglobin clearance capacity in Hp 2-2 DM
      individuals and may provide the key insight explaining the increased incidence of
      myocardial infarction in this population.

PMID- 17525368
TI  - Enhancing repair of the mammalian heart.
AB  - The injured mammalian heart is particularly susceptible to tissue deterioration,
      scarring, and loss of contractile function in response to trauma or sustained
      disease. We tested the ability of a locally acting insulin-like growth factor-1
      isoform (mIGF-1) to recover heart functionality, expressing the transgene in the
      mouse myocardium to exclude endocrine effects on other tissues. supplemental mIGF
      1 expression did not perturb normal cardiac growth and physiology. Restoration of
      cardiac function in post-infarct mIGF-1 transgenic mice was facilitated by
      modulation of the inflammatory response and increased antiapoptotic signaling.
      mIGF-1 ventricular tissue exhibited increased proliferative activity several
      weeks after injury. The canonical signaling pathway involving Akt, mTOR, and
      p70S6 kinase was not induced in mIGF-1 hearts, which instead activated alternate
      PDK1 and SGK1 signaling intermediates. The robust response achieved with the mIGF
      1 isoform provides a mechanistic basis for clinically feasible therapeutic
      strategies for improving the outcome of heart disease.

PMID- 17525369
TI  - Flow antagonizes TNF-alpha signaling in endothelial cells by inhibiting caspase
      dependent PKC zeta processing.
AB  - Unidirectional laminar flow is atheroprotective, in part by inhibiting cytokine
      mediated endothelial cell (EC) inflammation and apoptosis. Previously, we showed
      that flow inhibited TNF-alpha signaling by preventing activation of JNK.
      Recently, PKCzeta was identified as the PKC isoform most strongly regulated by
      flow pattern, with increased PKCzeta activity in regions of disturbed flow versus
      unidirectional flow. Interestingly, PKCzeta is cleaved by caspases after TNF
      alpha stimulation to generate a 50-kDa truncated form (CATzeta, catalytic domain
      of PKCzeta) with a higher kinase activity than the full-length protein. We
      hypothesized that flow would inhibit TNF-alpha-mediated PKCzeta cleavage and
      thereby CATzeta formation. We found that PKCzeta activity was required for TNF
      alpha-mediated JNK and caspase-3 activation in ECs. PKCzeta was rapidly cleaved
      to generate CATzeta in cultured bovine and human aortic ECs and in intact rabbit
      vessels stimulated with TNF-alpha. This truncated form of PKCzeta enhanced JNK
      and caspase-3 activation. Interestingly, PKCzeta cleavage was prevented by
      inhibitors of PKCzeta, JNK, and caspase activities, suggesting that these
      enzymes, via regulating CATzeta formation, modulate caspase-3 activity in ECs.
      Finally, we found that flow reduced caspase-dependent processing of PKCzeta and
      caspase-3 activation. These results define a novel role for PKCzeta as a shared
      signaling mediator for flow and TNF-alpha, and important for flow-mediated
      inhibition of proinflammatory and apoptotic events in ECs.

PMID- 17525370
TI  - Dominant negative suppression of Rad leads to QT prolongation and causes
      ventricular arrhythmias via modulation of L-type Ca2+ channels in the heart.
AB  - Disorders of L-type Ca2+ channels can cause severe cardiac arrhythmias. A
      subclass of small GTP-binding proteins, the RGK family, regulates L-type Ca2+
      current (I(Ca,L)) in heterologous expression systems. Among these proteins, Rad
      (Ras associated with diabetes) is highly expressed in the heart, although its
      role in the heart remains unknown. Here we show that overexpression of dominant
      negative mutant Rad (S105N) led to an increase in I(Ca,L) and action potential
      prolongation via upregulation of L-type Ca2+ channel expression in the plasma
      membrane of guinea pig ventricular cardiomyocytes. To verify the in vivo
      physiological role of Rad in the heart, a mouse model of cardiac-specific Rad
      suppression was created by overexpressing S105N Rad, using the alpha-myosin heavy
      chain promoter. Microelectrode studies revealed that action potential duration
      was significantly prolonged with visible identification of a small plateau phase
      in S105N Rad transgenic mice, when compared with wild-type littermate mice.
      Telemetric electrocardiograms on unrestrained mice revealed that S105N Rad
      transgenic mice had significant QT prolongation and diverse arrhythmias such as
      sinus node dysfunction, atrioventricular block, and ventricular extrasystoles,
      whereas no arrhythmias were observed in wild-type mice. Furthermore,
      administration of epinephrine induced frequent ventricular extrasystoles and
      ventricular tachycardia in S105N Rad transgenic mice. This study provides novel
      evidence that the suppression of Rad activity in the heart can induce ventricular
      tachycardia, suggesting that the Rad-associated signaling pathway may play a role
      in arrhythmogenesis in diverse cardiac diseases.

PMID- 17525371
TI  - RhoGDI-1 modulation of the activity of monomeric RhoGTPase RhoA regulates
      endothelial barrier function in mouse lungs.
AB  - Rho family GTPases have been implicated in the regulation of endothelial
      permeability via their actions on actin cytoskeletal organization and integrity
      of interendothelial junctions. In cell culture studies, activation of RhoA
      disrupts interendothelial junctions and increases endothelial permeability,
      whereas activation of Rac1 and Cdc42 enhances endothelial barrier function by
      promoting the formation of restrictive junctions. The primary regulators of Rho
      proteins, guanine nucleotide dissociation inhibitors (GDIs), form a complex with
      the GDP-bound form of the Rho family of monomeric G proteins, and thus may serve
      as a nodal point regulating the activation state of RhoGTPases. In the present
      study, we addressed the in vivo role of RhoGDI-1 in regulating pulmonary
      microvascular permeability using RhoGDI-1(-/-) mice. We observed that basal
      endothelial permeability in lungs of RhoGDI-1(-/-) mice was 2-fold greater than
      wild-type mice. This was the result of opening of interendothelial junctions in
      lung microvessels which are normally sealed. The activity of RhoA (but not of
      Rac1 or Cdc42) was significantly increased in RhoGDI-1(-/-) lungs as well as in
      cultured endothelial cells on downregulation of RhoGDI-1 with siRNA, consistent
      with RhoGDI-1-mediated modulation RhoA activity. Thus, RhoGDI-1 by repressing
      RhoA activity regulates lung microvessel endothelial barrier function in vivo. In
      this regard, therapies augmenting endothelial RhoGDI-1 function may be beneficial
      in reestablishing the endothelial barrier and lung fluid balance in lung
      inflammatory diseases such as acute respiratory distress syndrome.

PMID- 17525372
TI  - Diabetes, ubiquitin proteasome system and atherosclerotic plaque rupture.

PMID- 17525373
TI  - The endothelial protein C receptor in vascular smooth muscle cells for good or
      bad?

PMID- 17525374
TI  - The challenge of genetic studies in hypertension.

PMID- 17525375
TI  - Peroxisome proliferator-activated receptors mediate pleiotropic actions of
      statins.

PMID- 17525376
TI  - Do we age on Sirt1 expression?

PMID- 17525377
TI  - New insights into the developmental biomechanics of the atrioventricular valves.

PMID- 17525378
TI  - Silky, sticky chimeras-designer VEGFs display their wares.

PMID- 17525379
TI  - C-reactive protein and reendothelialization: NO involvement.

PMID- 17525380
TI  - Integrin-linked kinase at the heart of cardiac contractility, repair, and
      disease.
AB  - Recent advances in cardiac physiology identify the integrin-linked kinase (ILK)
      as an essential molecule regulating cardiac growth, contractility, and repair. A
      key transducer of biochemical signals initiated at the plasma membrane by cell
      matrix interactions, ILK now emerges as a crucial player in mechanotransduction
      by integrins. Animal models have been particularly instructive in dissecting the
      cardiac functions of ILK and its associated proteins, such as parvins and PINCH,
      and have clearly established ILK as a major contributor to cardiac health. ILK
      gene knockouts in mice, flies, and worms result in early embryonic lethality
      because of cell adhesion defects and cytoskeletal disorganization. Although
      widely distributed in mammalian tissues, ILK expression is highest in the heart,
      and cardiac-specific ablation of ILK causes cardiomyopathy and sudden death in
      mice. ILK protein complexes are found in the sarcomere, which is the basic
      contractile unit of myocytes. A natural inactivating mutation in the kinase
      domain of ILK disrupts ILK protein interactions in the sarcomere, causing a
      contractile defect in the zebrafish heart. The relatively subtle phenotype of
      mutant ILK hearts, compared with ILK-ablated hearts, suggests multiple cardiac
      ILK functions. Cardiac-specific expression of ILK in transgenic mice induces a
      hypertrophic program, pointing to ILK as a proximal regulator of multiple
      hypertrophic signal transduction pathways. ILK protein interactions may also be
      important in mediating postinfarct cell migration and myocardial repair.

PMID- 17525381
TI  - Recipes for creating animal models of diabetic cardiovascular disease.
AB  - For more than 50 years, investigators have unsuccessfully tried to recreate in
      experimental animals the cardiovascular complications of diabetes seen in humans.
      In particular, accelerated atherosclerosis and dilated cardiomyopathy, the major
      causes of mortality in patients with diabetes, have been conspicuously absent in
      many mouse models of the disease. Under the auspices of the NIH, the Animal
      Models of Diabetic Complications Consortium has worked to address this issue.
      This effort has focused on the development of mouse models because of the high
      level of genomic information available and the many well-developed genetic
      manipulations that may be performed in mice. Importantly, the consortium has also
      worked to standardize many methods to assess metabolic and cardiovascular end
      points for measurement of the diabetic state and its macrovascular complications.
      Finally, for maximum benefits from these animal models in the study of
      atherosclerosis and of other diabetic complications, the consortium has created a
      system for sharing both the animal models and the accumulated phenotypic data
      with the greater scientific community.

PMID- 17525382
TI  - Programming smooth muscle plasticity with chromatin dynamics.
AB  - Smooth muscle cells (SMCs) possess remarkable phenotypic plasticity that allows
      rapid adaptation to fluctuating environmental cues. For example, vascular SMCs
      undergo profound changes in their phenotype during neointimal formation in
      response to vessel injury or within atherosclerotic plaques. Recent studies have
      shown that interaction of serum response factor (SRF) and its numerous accessory
      cofactors with CArG box DNA sequences within promoter chromatin of SMC genes is a
      nexus for integrating signals that influence SMC differentiation in development
      and disease. During development, SMC-restricted sets of posttranslational histone
      modifications are acquired within the CArG box chromatin of SMC genes. These
      modifications in turn control the chromatin-binding properties of SRF. The
      histone modifications appear to encode a SMC-specific epigenetic program that is
      used by extracellular cues to influence SMC differentiation, by regulating
      binding of SRF and its partners to the chromatin template. Thus, SMC
      differentiation is dynamically regulated by the interplay between SRF accessory
      cofactors, the SRF-CArG interaction, and the underlying histone modification
      program. As such, the inherent plasticity of the SMC lineage offers unique
      glimpses into how cellular differentiation is dynamically controlled at the level
      of chromatin within the context of changing microenvironments. Further
      elucidation of how chromatin regulates SMC differentiation will undoubtedly yield
      valuable insights into both normal developmental processes and the pathogenesis
      of several vascular diseases that display detrimental SMC phenotypic behavior.

PMID- 17525383
TI  - Apolipoprotein E in hypercholesteremia and beyond.

PMID- 17525384
TI  - Stroke symptoms and the decision to call for an ambulance: turn on people's
      minds!

PMID- 17525385
TI  - Retinal microvascular signs, cognitive function, and dementia in older persons:
      the Cardiovascular Health Study.
AB  - BACKGROUND AND PURPOSE: Cerebral microvascular disease may be a risk factor for
      the development of dementia in elderly persons. We describe the association of
      retinal microvascular signs with cognitive function and dementia among older
      individuals. METHODS: In the population-based Cardiovascular Health Study, 2211
      persons aged 69 to 97 years at recruitment had retinal photography. Photographs
      were evaluated for retinopathy (eg, microaneurysms, retinal hemorrhages), focal
      arteriolar narrowing, arteriovenous nicking, and retinal arteriolar and venular
      caliber. Cognitive status was determined from the Digit-Symbol Substitution Test
      and Modified Mini-Mental State Examination. Participants were also further
      evaluated for the presence of dementia with detailed neuropsychological testing.
      Persons with a prior stroke or taking antipsychotic or antidepressant medications
      were excluded. RESULTS: After adjusting for age, gender, race, field center,
      education level, internal carotid intima-media thickness, body mass index,
      hypertension, diabetes, and cigarette smoking status, persons with retinopathy
      had lower mean Digit-Symbol Substitution Test scores but not Modified Mini-Mental
      State Examination than those without retinopathy (39 versus 41, P=0.002). In
      hypertensive persons, retinopathy (multivariable-adjusted OR, 2.10; 95% CI, 1.04
      to 4.24) and focal arteriolar narrowing (OR, 3.02; 95% CI, 1.51 to 6.02) were
      associated with dementia. These associations were not present in individuals
      without hypertension. CONCLUSIONS: In older persons, our study shows a modest
      cross-sectional association between retinopathy signs with poorer cognitive
      function and, in persons with hypertension, with dementia. These data support a
      possible role of cerebral microvascular disease in the pathogenesis of impaired
      cognitive function and dementia in older hypertensive persons.

PMID- 17525386
TI  - Intravenous thrombolysis for acute ischemic stroke after vitrectomy for retinal
      detachment.

PMID- 17525387
TI  - The Interventional Management of Stroke (IMS) II Study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to further investigate the
      feasibility and safety of a combined intravenous and intra-arterial approach to
      recanalization for ischemic stroke. METHODS: Subjects, ages 18 to 80, with a
      baseline NIHSS > or =10 had intravenous recombinant tissue plasminogen activator
      (rt-PA) started (0.6 mg/kg over 30 minutes) within 3 hours of onset. For subjects
      with an arterial occlusion at angiography, additional rt-PA was administered via
      the EKOS micro-infusion catheter or a standard microcatheter at the site of the
      thrombus up to a total dose of 22 mg over 2 hours of infusion or until
      thrombolysis. RESULTS: The 81 subjects had a median baseline NIHSS score of 19.
      The median time to initiation of intravenous rt-PA was 142 minutes as compared
      with 108 minutes for placebo and 90 minutes for rt-PA-treated subjects in the
      NINDS rt-PA Stroke Trial (P<0.0001). The 3-month mortality in IMS II subjects was
      16% as compared with the mortality of placebo (24%) and rt-PA-treated subjects
      (21%) in the NINDS rt-PA Stroke Trial. The rate of symptomatic intracerebral
      hemorrhage in IMS II subjects (9.9%) was not significantly different than that
      for rt-PA treated subjects in the NINDS t-PA Stroke Trial (6.6%). IMS II subjects
      had significantly better outcomes at 3 months than NINDS placebo-treated subjects
      for all end points (OR > or =2.7) and better outcomes than NINDS rt-PA-treated
      subjects as measured by the Barthel Index and Global Test Statistic. CONCLUSIONS:
      A randomized trial of standard intravenous rt-PA as compared with a combined
      intravenous and intra-arterial approach is warranted and has begun.

PMID- 17525388
TI  - Early arterial study in the prediction of mortality after acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the value of
      the initial arterial study as a predictor of 90-day mortality in patients with
      acute ischemic stroke. METHODS: A total of 1220 unselected patients assessed
      during the first 24 hours after stroke onset were prospectively studied. Initial
      stroke severity was evaluated by the National Institutes of Health Stroke Scale
      and dichotomized in mild (National Institutes of Health Stroke Scale < or =7) and
      severe (National Institutes of Health Stroke Scale >7). Severe arterial stenosis
      (> or =70%) or arterial occlusion in the symptomatic territory was determined by
      a Doppler study and also by additional explorations (carotid duplex, MR or CT
      angiography) in the first 24 hours after admission. The following variables were
      also analyzed: age, gender, previous functional status, smoking, hypertension,
      hyperlipidemia, diabetes mellitus, peripheral arterial disease, ischemic heart
      disease, heart failure, atrial fibrillation, previous stroke, and prior use of
      antithrombotic or statins. Ninety-day mortality was the end point of the study.
      RESULTS: Ninety-day mortality was 15.7%. A total of 25.5% of all deaths were in
      patients with mild stroke. In addition to well-known factors related to mortality
      (age, stroke severity, ischemic heart disease, heart failure, and previous
      disability), severe arterial stenosis/occlusion was the factor with the highest
      relationship with 90-day mortality (adjusted OR: stenosis 2.13, occlusion 4.42,
      both 3.36). Arterial stenosis/occlusion was a higher predictor of 90-day
      mortality in patients with mild (adjusted OR: 5.38) than severe stroke (adjusted
      OR: 3.05). CONCLUSIONS: Severe arterial stenosis/occlusion in the early arterial
      study was highly related with 90-day mortality in an unselected series of
      patients with stroke. These data achieve special relevance in patients with
      initial mild stroke.

PMID- 17525389
TI  - Risk of acute brain injury related to cerebral microembolism during cardiac
      catheterization performed by right upper limb arterial access.
AB  - BACKGROUND AND PURPOSE: The primary objective of this study was to assess the
      incidence of new cerebral infarcts related to cardiac catheterization in patients
      explored through the right transradial approach. METHODS: This prospective study
      involved 41 consecutive patients with severe aortic valve stenosis. To assess the
      incidence of cerebral infarction, all patients underwent cerebral diffusion
      weighted MRI before and after cardiac catheterization through the right
      transradial approach. RESULTS: We detected only two patients (4.9%) with new,
      small, isolated acute cerebral diffusion abnormalities postcatheterization. All
      patients remained asymptomatic. CONCLUSIONS: New cerebral lesions on diffusion
      weighted MRI are infrequent in patients explored through the right transradial
      approach. Randomized studies are warranted to confirm for potential advantages of
      transradial approach versus the femoral approach in cardiac catheterization.

PMID- 17525390
TI  - Cerebral vascular dysfunction during hypercholesterolemia.
AB  - BACKGROUND AND PURPOSE: Studies of peripheral arteries in hypercholesterolemic
      animals suggest that increased generation of superoxide contributes to
      endothelial dysfunction, especially in the presence of atherosclerotic lesions.
      We tested the hypothesis that vasomotor function is impaired in cerebral
      arterioles during hypercholesterolemia through a mechanism that involves
      oxidative stress. METHODS: Apolipoprotein E-deficient (apoE(-/-)) mice were fed a
      normal or a high-fat diet for >6 months. ApoE(+/-) mice fed a normal diet were
      used as normocholesterolemic controls. Responses of cerebral arterioles were
      examined in open cranial windows in vivo in anesthetized mice. RESULTS: In apoE(
      /-) mice, intimal area was increased only in the proximal aorta on the normal
      diet and also markedly increased in the distal aorta on the high-fat diet. There
      were no increases in intimal area in the aortas of control mice or in the
      cerebral arterioles in any group. The dilator response of cerebral arterioles to
      ACh (10 micromol/L) in control mice (26+/-4% increase in diameter) was reduced in
      apoE(-/-) mice on either the normal (13+/-2%) or the high-fat (13+/-3%) diet
      (P<0.05 vs control). NADPH (10 micromol/L), a substrate for NADPH oxidase,
      produced dilator responses in control mice (8+/-4%) that were significantly
      increased in apoE(-/-) mice on the high-fat diet (16+/-2%, P<0.05 vs control).
      Tempol, a superoxide scavenger, and apocynin, an inhibitor of NADPH oxidase,
      significantly increased vasodilator responses to ACh and decreased vasodilation
      to NADPH in apoE(-/-) mice on the high-fat diet. Nitroprusside produced a similar
      dilatation in the cerebral arterioles of all groups. CONCLUSIONS:
      Hypercholesterolemia is associated with oxidative stress and endothelial
      dysfunction in cerebral arterioles, despite the absence of atherosclerotic
      lesions.

PMID- 17525391
TI  - One-year follow-up after bone marrow stromal cell treatment in middle-aged female
      rats with stroke.
AB  - BACKGROUND AND PURPOSE: We sought to evaluate the long-term effects of bone
      marrow stromal cell (BMSC) treatment on retired breeder rats with stroke.
      METHODS: Female retired breeder rats were subjected to 2-hour middle cerebral
      artery occlusion (MCAO) followed by an injection of 2 x 10(6) male BMSCs (n=8) or
      phosphate-buffered saline (n=11) into the ipsilateral internal carotid artery at
      1 day after stroke. The rats were humanely killed 1 year later. Functional tests,
      in situ hybridization, and histochemical and immunohistochemical staining were
      performed. RESULTS: Significant recovery of neurological deficits was found in
      BMSC-treated rats beginning 2 weeks after cell injection compared with control
      animals. The beneficial effects of cell transplantation persisted for at least 1
      year (P<0.01). In situ hybridization for the Y chromosome showed that donor cells
      survived in the brains of recipient rats, among which 22.3+/-1.95% of cells
      expressed the astrocyte marker glial fibrillary acidic protein, 16.8+/-2.13%
      expressed the neuronal marker microtubule-associated protein 2, and 5.5+/-0.42%
      and <1% of cells colocalized with the microglial marker IB4 and the endothelial
      cell marker von Willebrand factor, respectively. Only very few BMSCs, however,
      were found in peripheral organs such as the heart, lung, liver, spleen, and
      kidney in recipient rats. BMSCs significantly reduced axonal loss (P<0.01), the
      thickness of the lesion scar wall (P<0.01), and the number of Nogo-A-positive
      cells (P<0.05) along the scar border; meanwhile, synaptophysin expression
      (P<0.05) was significantly increased in BMSC-treated ischemic brains compared
      with control untreated brains. CONCLUSIONS: The beneficial effects of BMSCs on
      ischemic brain tissue persisted for at least 1 year. Most surviving BMSCs were
      present in the ischemic brain, but very few were found in other organs. The long
      term improvement in functional outcome may be related to the structural and
      molecular changes induced by BMSCs.

PMID- 17525392
TI  - Prothrombotic mutations as risk factors for cryptogenic ischemic cerebrovascular
      events in young subjects with patent foramen ovale.
AB  - BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) has been identified as a
      potential risk factor for cerebrovascular ischemia. Procoagulant mutations may
      increase the risk and impact the choice of appropriate therapy for secondary
      prevention. We evaluated the prevalence of the 2 most common genetic risk factors
      for thromboembolism, factor V Leiden (G1691A) and prothrombin G20210A, in young
      PFO patients who were referred for percutaneous transcatheter closure of their
      PFO. METHODS: Ninety-seven patients (50 men; mean+/-SD age, 40.9+/-10.0 years)
      with first-ever cerebrovascular events before the age of 55 years and 160 age
      matched control subjects (69 men; mean+/-SD age, 40.4+/-10.5 years) were
      recruited into the study. Factor V Leiden and prothrombin G20210A mutations were
      detected by using a multiplex allele-specific polymerase chain reaction assay.
      RESULTS: The prevalence of subjects carrying at least 1 prothrombotic genotype
      was significantly higher in the group of PFO patients than in the group of
      controls (10.3% vs 2.5%; chi(2)=7.2, P=0.008). Two patients (2.1%) versus 1
      control subject (0.6%) and 8 cases (8.2%) versus 3 controls (1.9%) were carriers
      for factor V Leiden and prothrombin G20210A mutations, respectively. After
      adjustment for other vascular risk factors, the combination of either factor V
      Leiden or prothrombin G20210A and PFO was associated with a 4.7-fold (95% CI=1.4
      to 16.1; P=0.008) increased risk of cerebral ischemia in young patients.
      CONCLUSIONS: Our results indicate that prothrombotic mutations are important risk
      factors for cerebral ischemia in young patients with PFO. Screening for
      thrombotic mutations should be considered in young patients with PFO-related
      ischemic events.

PMID- 17525393
TI  - Increased echolucency of carotid plaques in patients with type 2 diabetes.
AB  - BACKGROUND AND PURPOSE: Diabetes is associated with the presence of moderate to
      large atherosclerotic carotid plaques. Previous carotid ultrasound studies have
      associated plaques with low echogenicity with a higher risk of cerebrovascular
      events. The aim of this study was to evaluate whether patients with type 2
      diabetes have different plaque echogenicity than do nondiabetic subjects.
      METHODS: Forty-seven type 2 diabetic and 51 nondiabetic subjects with a carotid
      plaque in the right artery were included in this study. All patients were born in
      1935 to 1936 and were participants in a population-based study. Carotid
      ultrasonography was performed and the risk factors for cardiovascular disease
      were determined. Plaque echogenicity was assessed quantitatively on B-mode
      ultrasound images by standardized gray-scale median values. RESULTS: Gray-scale
      median values were significantly lower, indicating more echolucent plaques, in
      patients with type 2 diabetes compared with nondiabetics (37.0+/-14.8 vs 45.5+/
      15.4, P=0.007). Of the other risk factors studied, only triglycerides were
      significantly associated with the echogenicity of the plaque. CONCLUSIONS:
      Patients with type 2 diabetes have more echolucent plaques compared with
      nondiabetic subjects. This might be associated with the higher risk of
      cardiovascular events among diabetics.

PMID- 17525394
TI  - Enhanced thrombogenesis is physiologic after transcatheter closure of patent
      foramen ovale.

PMID- 17525395
TI  - A pilot study of dual treatment with recombinant tissue plasminogen activator and
      uric acid in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Uric acid (UA) increases the neuroprotective effects of
      recombinant tissue plasminogen activator (rt-PA) in experimental ischemia. In
      patients with stroke, increased UA levels have been linked to better stroke
      recovery, but the clinical safety of dual administration of UA and rt-PA is
      unknown. METHODS: Using a double-blind design, we assessed the safety of
      exogenous UA in patients with acute stroke treated with rt-PA. Patients were
      randomized to an intravenous solution of 500 mL of 5% mannitol/0.1% lithium
      carbonate (vehicle group, n=8) or 500 or 1000 mg of UA (n=16). Safety end points
      at day 90, lipid peroxidation (serum malondialdehyde), and serum kinetics of UA
      were established. RESULTS: Twenty-four patients with stroke were treated with rt
      PA within mean (SD) 133 (35) minutes of clinical onset (admission National
      Institutes of Health Stroke Scale score mean [SD] 11 [7], age 71 [10.6] years,
      71% males). Levels of UA decreased in the vehicle group and increased for
      approximately 24 hours in the high dose of UA group, which also had lower levels
      of malondialdehyde at day 5. Mortality (12.5%), symptomatic central nervous
      system bleeding (0%), and outcome at day 90 were similar in the 3 treatment arms;
      one patient in the high-dose group had a mild gouty episode. CONCLUSIONS: The
      administration of UA appears to be safe, decreases lipid peroxidation, and
      prevents an early fall of UA in serum in patients treated with rt-PA within 3
      hours of stroke onset. The clinical efficacy of dual administration of exogenous
      UA and rt-PA deserves further investigation in a larger acute stroke trial.

PMID- 17525396
TI  - Impact of metabolic syndrome on the development of cardiovascular disease in a
      general Japanese population: the Hisayama study.
AB  - BACKGROUND AND PURPOSE: The metabolic syndrome (MetS) is associated with an
      increased risk of cardiovascular disease (CVD) events in general populations.
      However, well-designed prospective studies in Asian populations are very limited.
      METHODS: We prospectively evaluated a total of 2452 community-dwelling Japanese
      individuals aged 40 years or older from 1988 to 2002 and examined the effects of
      MetS defined by the modified National Cholesterol Education Program Adult
      Treatment Panel III criteria on incident CVD. RESULTS: The prevalence of the MetS
      was 21% in men and 30% in women at baseline. During the follow up, 307 CVD events
      occurred. Compared with those without MetS, the age-adjusted incidence of CVD
      (per 1000 person-years) was significantly higher in subjects with the MetS in
      both men (21.8 versus 11.6, P<0.01) and women (12.9 versus 6.5, P<0.01). The risk
      of CVD events was significantly higher even after adjusting for the following
      confounding factors: age, proteinuria, electrocardiographic abnormalities, serum
      total cholesterol, smoking habits, alcohol intake, and regular exercise (hazard
      ratio, 1.86; 95% CI, 1.32 to 2.62 in men and hazard ratio, 1.70; 95% CI, 1.22 to
      2.36 in women). The risk of incident CVD was found to increase with the number of
      components of MetS and became significantly predictive when the number of
      components reached 3. Similar associations were also observed when CVD was
      divided into coronary heart disease and stroke. CONCLUSIONS: Our findings suggest
      that MetS is a significant risk factor for the development of CVD in the Japanese
      middle-aged population.

PMID- 17525397
TI  - Evaluation of fatigue scales in stroke patients.
AB  - BACKGROUND AND PURPOSE: There is little information on how to best measure
      poststroke fatigue. Our aim was to identify which currently available fatigue
      scale is most valid, feasible, and reliable in stroke patients. METHODS: Fatigue
      scales were identified by systematic search, and the 5 with the best face
      validity were identified by expert consensus. Feasibility (ie, did patients
      provide answers?) and internal consistency (an aspect of reliability) of these
      scales were evaluated by interviewing 55 stroke patients. Test-retest reliability
      was assessed by reinterviewing 51 patients, interrater reliability was assessed
      by rerating audio recordings, and convergent validity was assessed by measuring
      the correlation between scale scores. RESULTS: Of the 52 scales identified, the
      SF-36v2 (vitality component), the fatigue subscale of the Profile of Mood States,
      the Fatigue Assessment Scale, the general subscale of the Multidimensional
      Fatigue Symptom Inventory, and the Brief Fatigue Inventory had the best face
      validity. The Brief Fatigue Inventory was unfeasible to administer and was
      omitted. Of the remaining 4 scales, the Fatigue Assessment Scale had the poorest
      internal consistency. Test-retest reliability for individual scale questions
      ranged from fair to good; the Fatigue Assessment Scale had the narrowest limits
      of agreement for the total score, indicating the best test-retest reliability.
      Interrater reliability for individual questions ranged from good to very good,
      and there was no significant mean difference in total scores for any scale.
      Convergent validity was moderate to high for the total scores of the 4 scales.
      CONCLUSIONS: All four scales were valid and feasible to administer to stroke
      patients. The Fatigue Assessment Scale had the best test-retest reliability but
      the poorest internal consistency.

PMID- 17525398
TI  - Sex disparity in the access of elderly patients to acute stroke care.
AB  - BACKGROUND AND PURPOSE: Sex differences in the management of acute coronary
      symptoms are well documented. We sought to determine whether sex disparities
      exist in acute stroke management, particularly with regard to early hospital
      admission and thrombolytic therapy. METHODS: We analyzed a prospective,
      countywide, hospital-based stroke registry. Between 1999 and 2005, all cases with
      a final diagnosis of cerebral infarction (ICD-10 I63) or intracerebral hemorrhage
      (ICD-10 I61) were selected. Datasets with missing values for sex and time to
      admission, as well as datasets of patients transferred between hospitals in the
      acute phase, were excluded. Main outcome measures were the probability of being
      admitted within the first 3 hours of stroke onset and being treated with
      thrombolytic agents for both women and men, after adjustment for age, prestroke
      disability, severity of clinical symptoms, vascular risk factors, and final
      diagnosis. RESULTS: Fifty-three thousand four hundred fourteen patients were
      included (49.3% female; mean+/-SD age, 72.1+/-12.5 years). Women had a 10% lower
      chance of being admitted within the first 3 hours than men (odds ratio=0.902, 95%
      CI=0.860 to 0.945, P<0.001). This chance further decreased in elderly women.
      Similarly, the chance of a female stroke patient being treated with thrombolysis
      was 13% lower than that of a male patient (odds ratio=0.867, 95% CI=0.782 to
      0.960, P=0.006). For patients admitted within the 3-hour time window, the chance
      of being treated with thrombolysis was similar for women and men (odds
      ratio=0.915, 95% CI=0.809 to 1.035, P=0.156). CONCLUSIONS: We identified sex
      disparities in acute stroke management in terms of early hospital admission and
      thrombolytic treatment. This is best explained by the sociodemographic fact that
      "surviving spouses" are more likely to be women than men. Attempts to overcome
      disadvantages in their access to acute stroke care should focus on increased
      social support.

PMID- 17525399
TI  - Effect of gender on NADPH-oxidase activity, expression, and function in the
      cerebral circulation: role of estrogen.
AB  - BACKGROUND AND PURPOSE: This study tested whether NADPH-oxidase activity,
      expression, and functional effects on vascular tone are influenced by gender in
      the rat cerebral circulation and whether such differences are estrogen-dependent.
      METHODS: NADPH-stimulated superoxide production by cerebral (basilar [BA]; middle
      cerebral) arteries from male and female Sprague-Dawley rats was measured using
      lucigenin-enhanced chemiluminescence and dihydroethidium. Protein expression of
      Nox1, Nox2, Nox4, superoxide dismutase 1 (SOD1), SOD2, and SOD3 was measured
      using Western blotting. Vascular responses of BA to NADPH were assessed in a
      myograph. Some female rats were ovariectomized and treated with either vehicle
      (dimethyl sulfoxide) or 17beta-estradiol. RESULTS: NADPH-stimulated superoxide
      production by BA and middle cerebral arteries from males was approximately 2-fold
      greater than vessels from females. Superoxide production was virtually abolished
      by the NADPH-oxidase inhibitor, diphenyleneiodonium. Protein expression of Nox1
      and Nox4 in BA was also higher in males than in females (2.4- and 2.8-fold,
      respectively), whereas Nox2, SOD1, SOD2, and SOD3 expression did not differ
      between genders. NADPH induced greater vasorelaxant effects in BA from males
      versus females (P<0.05). The hydrogen peroxide scavenger, catalase, abolished
      these NADPH-induced relaxations. NADPH-stimulated superoxide production by BA
      from ovariectomized rats treated with vehicle was 3-fold greater than levels in
      intact females. Treatment of ovariectomized rats with 17beta-estradiol decreased
      superoxide production (P<0.05). NADPH-induced relaxations of BA were smaller in
      17beta-estradiol-treated than in vehicle-treated ovariectomized rats (P<0.05).
      CONCLUSIONS: NADPH-oxidase activity and function are lower in cerebral arteries
      of female rats. These gender differences are estrogen-dependent and are
      associated with lower Nox1 and Nox4 expression.

PMID- 17525400
TI  - Changes in cost and outcome among US patients with stroke hospitalized in 1990 to
      1991 and those hospitalized in 2000 to 2001.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the impact of
      new treatments by examining the changes between 1990 to 1991 and 2000 to 2001 in
      in-hospital mortality rates and hospital charges in adult patients with stroke.
      METHODS: From the Nationwide Inpatient Survey, the largest all-payer inpatient
      care database in the United States, patients with stroke admitted in 1990 to 1991
      or 2000 to 2001 were studied. We analyzed hospital charges (adjusted for
      inflation based on the Consumer Price Index of the Bureau of Labor Statistics)
      and patient outcomes by type of institution: rural, urban nonteaching, and urban
      teaching in 1990 to 1991 and in 2000 to 2001. RESULTS: In 1990 to 1991, there
      were 1 736 352 admissions for cerebrovascular diseases, and in 2000 to 2001,
      there were 1 958 018 admissions. The number of admissions in urban teaching
      hospitals increased by 13%, 19%, and 25%, for ischemic stroke, intracerebral
      hemorrhage, and subarachnoid hemorrhage, respectively. The overall in-hospital
      mortality rate relatively declined by 36% for ischemic stroke, by 6% for
      intracerebral hemorrhages, and by 10% for subarachnoid hemorrhage. The mean
      hospital charges increased from $10 500 to $16 200 for patients with ischemic
      stroke, from $18 300 to $28 800 for patients with intracerebral hemorrhage, and
      from $37 400 to $65 900 for patients with subarachnoid hemorrhage. Mortality
      rates among patients admitted after ischemic stroke, intracerebral hemorrhage,
      and subarachnoid hemorrhage were all lower in urban teaching hospitals than in
      rural and urban nonteaching hospitals and the mean charges per admission were all
      higher. CONCLUSIONS: There has been an increase in the inflation-adjusted
      hospital charges for all patients with stroke and a reduction in mortality rates
      for all stroke subtypes probably related to an increase in the proportion of
      patients with stroke admitted to urban teaching hospitals.

PMID- 17525401
TI  - Intestinal nematode infection and anaemia in developing countries.

PMID- 17525402
TI  - The role of pharmacists in primary care.

PMID- 17525403
TI  - The future of specialist training.

PMID- 17525404
TI  - Rationing in the NHS.

PMID- 17525405
TI  - Antipsychotic drugs in children with autism.

PMID- 17525406
TI  - Government proposals conflict.

PMID- 17525407
TI  - Global triage of global resources needed.

PMID- 17525408
TI  - Too little, too late?

PMID- 17525409
TI  - Ends never justify means.

PMID- 17525410
TI  - Are we asking the right questions?

PMID- 17525411
TI  - Article is concerning.

PMID- 17525412
TI  - Doctors condemn use of drugs as weapons.

PMID- 17525413
TI  - Study indicates diabetes drug linked to cardiovascular death.

PMID- 17525416
TI  - UK government prepares way for creation of hybrid embryos for research.

PMID- 17525417
TI  - Incidence of euthanasia in the Netherlands falls as that of palliative sedation
      rises.

PMID- 17525418
TI  - Judicial review will decide trainees' future.

PMID- 17525419
TI  - Cost of some types of prescribed drug can vary fourfold across England, audit
      shows.

PMID- 17525420
TI  - Developing countries need stronger ethical guidelines on research.

PMID- 17525421
TI  - Croatian academic is found guilty of plagiarism.

PMID- 17525423
TI  - US comes last in international comparison of health systems.

PMID- 17525424
TI  - Remedy UK loses court case over doctors' training applications.

PMID- 17525425
TI  - Academics should use their intellectual property to produce cheap drugs for poor
      countries.

PMID- 17525427
TI  - Patients with cancer could spend less time in hospital, says tsar.

PMID- 17525428
TI  - US agency limits payments for anaemia drugs.

PMID- 17525429
TI  - Research ethics have not "sunk to an all time low".

PMID- 17525431
TI  - Keeping the scientists in step with society.

PMID- 17525445
TI  - Protection for the innocent.

PMID- 17525446
TI  - Great health care, guaranteed.

PMID- 17525449
TI  - Is presumed consent the answer to organ shortages? Yes.

PMID- 17525450
TI  - Is presumed consent the answer to organ shortages? No.

PMID- 17525451
TI  - Requests for cosmetic genitoplasty: how should healthcare providers respond?

PMID- 17525452
TI  - Primary care research networks in the United Kingdom.

PMID- 17525453
TI  - Psychological approach to managing irritable bowel syndrome.

PMID- 17525454
TI  - Dysfunctional uterine bleeding.

PMID- 17525455
TI  - Secondary prevention for patients after a myocardial infarction: summary of NICE
      guidance.

PMID- 17525461
TI  - Single molecule analyses of the conformational substates of calmodulin bound to
      the phosphorylase kinase complex.
AB  - The four integral delta subunits of the phosphorylase kinase (PhK) complex are
      identical to calmodulin (CaM) and confer Ca(2+) sensitivity to the enzyme, but
      bind independently of Ca(2+). In addition to binding Ca(2+), an obligatory
      activator of PhK's phosphoryltransferase activity, the delta subunits transmit
      allosteric signals to PhK's remaining alpha, beta, and gamma subunits in
      activating the enzyme. Under mild conditions about 10% of the delta subunits can
      be exchanged for exogenous CaM. In this study, a CaM double-mutant derivatized
      with a fluorescent donor-acceptor pair (CaM-DA) was exchanged for delta to assess
      the conformational substates of PhKdelta by single molecule fluorescence
      resonance energy transfer (FRET) +/-Ca(2+). The exchanged subunits were
      determined to occupy distinct conformations, depending on the absence or presence
      of Ca(2+), as observed by alterations of the compact, mid-length, and extended
      populations of their FRET distance distributions. Specifically, the combined
      predominant mid-length and less common compact conformations of PhKdelta became
      less abundant in the presence of Ca(2+), with the delta subunits assuming more
      extended conformations. This behavior is in contrast to the compact forms
      commonly observed for many of CaM's Ca(2+)-dependent interactions with other
      proteins. In addition, the conformational distributions of the exchanged PhKdelta
      subunits were distinct from those of CaM-DA free in solution, +/-Ca(2+), as well
      as from exogenous CaM bound to the PhK complex as delta'. The distinction between
      delta and delta' is that the latter binds only in the presence of Ca(2+), but
      stoichiometrically and at a different location in the complex than delta.

PMID- 17525462
TI  - Molecular dynamics simulations of the native and partially folded states of
      ubiquitin: influence of methanol cosolvent, pH, and temperature on the protein
      structure and dynamics.
AB  - A series of explicit-solvent molecular dynamics simulations of the protein
      ubiquitin are reported, which investigate the effect of environmental factors
      (presence of methanol cosolvent in the aqueous solution, neutral or low pH value,
      room or elevated temperature) on the structure, stability, and dynamics of the
      protein. The simulations are initiated either from the native structure of the
      protein or from a model of a partially folded state (A-state) that is known to
      exist at low pH in methanol-water mixtures. The main results of the simulations
      are: (1) The ubiquitin native structure is remarkably stable at neutral pH in
      water; (2) the addition of the methanol cosolvent enhances the stability of the
      secondary structure but weakens tertiary interactions within the protein; (3)
      this influence of methanol on the protein structure is enhanced at low pH, while
      the effect of lowering the pH in pure water is limited; and (4) the A-state of
      ubiquitin can be described as a set of relatively rigid secondary structure
      elements (a native-like beta-sheet and native-like alpha-helix plus two nonnative
      alpha-helices) connected by flexible linkers.

PMID- 17525463
TI  - High-resolution structures of formate dehydrogenase from Candida boidinii.
AB  - The understanding of the mechanism of enzymatic recovery of NADH is of biological
      and of considerable biotechnological interest, since the essential, but
      expensive, cofactor NADH is exhausted in asymmetric hydrogenation processes, but
      can be recovered by NAD(+)-dependent formate dehydrogenase (FDH). Most accepted
      for this purpose is the FDH from the yeast Candida boidinii (CbFDH), which,
      having relatively low thermostability and specific activity, has been targeted by
      enzyme engineering for several years. Optimization by mutagenesis studies was
      performed based on physiological studies and structure modeling. However, X-ray
      structural information has been required in order to clarify the enzymatic
      mechanism and to enhance the effectiveness and operational stability of enzymatic
      cofactor regenerators in biocatalytic enantiomer synthesis as well as to explain
      the observed biochemical differences between yeast and bacterial FDH. We designed
      two single-point mutants in CbFDH using an adapted surface engineering approach,
      and this allowed crystals suitable for high-resolution X-ray structural studies
      to be obtained. The mutations improved the crystallizability of the protein and
      also the catalytic properties and the stability of the enzyme. With these crystal
      structures, we explain the observed differences from both sources, and form the
      basis for further rational mutagenesis studies.

PMID- 17525464
TI  - Probing interactions from solvent-exchangeable protons and monovalent cations
      with the 1,2-propanediol-1-yl radical intermediate in the reaction of
      dioldehydrase.
AB  - The reaction of adenosylcobalamin-dependent dioldehydrase with 1,2-propanediol
      gives rise to a radical intermediate observable by EPR spectroscopy. This
      reaction requires a monovalent cation such as potassium ion. The radical signal
      arises from the formation of a radical pair comprised of the Co(II) of
      cob(II)alamin and a substrate-related radical generated upon hydrogen abstraction
      by the 5'-deoxyadenosyl radical. The high-field asymmetric doublet arising from
      the organic radical has allowed investigation of its composition and environment
      through the use of EPR spectroscopic techniques. To characterize the protonation
      state of the oxygen substituents in the radical intermediate, X-band EPR
      spectroscopy was performed in the presence of D(2)O and compared to the spectrum
      in H(2)O. Results indicate that the unpaired electron of the steady-state radical
      couples to a proton on the C(1) hydroxyl group. Other spectroscopic experiments
      were performed, using either potassium or thallous ion as the activating
      monovalent cation, in an attempt to exploit the magnetic nature of the
      (205,203)Tl nucleus to identify any intimate interaction of the radical
      intermediate with the activating cation. The radical intermediate in complex with
      dioldehydrase, cob(II)alamin and one of the activating monovalent cations was
      observed using EPR, ENDOR, and ESEEM spectroscopy. The spectroscopic evidence did
      not implicate a direct coordination of the activating cation and the substrate
      derived radical intermediate.

PMID- 17525465
TI  - Identification of a potential hydrophobic peptide binding site in the C-terminal
      arm of trigger factor.
AB  - Trigger factor (TF) is the first chaperone to interact with nascent chains and
      facilitate their folding in bacteria. Escherichia coli TF is 432 residues in
      length and contains three domains with distinct structural and functional
      properties. The N-terminal domain of TF is important for ribosome binding, and
      the M-domain carries the PPIase activity. However, the function of the C-terminal
      domain remains unclear, and the residues or regions directly involved in
      substrate binding have not yet been identified. Here, a hydrophobic probe, bis
      ANS, was used to characterize potential substrate-binding regions. Results showed
      that bis-ANS binds TF with a 1:1 stoichiometry and a K(d) of 16 microM, and it
      can be covalently incorporated into TF by UV-light irradiation. A single bis-ANS
      labeled peptide was obtained by tryptic digestion and identified by MALDI-TOF
      mass spectrometry as Asn391-Lys392. In silico docking analysis identified a
      single potential binding site for bis-ANS on the TF molecule, which is adjacent
      to this dipeptide and lies in the pocket formed by the C-terminal arms. The bis
      ANS-labeled TF completely lost the ability to assist GAPDH or lysozyme refolding
      and showed increased protection toward cleavage by alpha-chymotrypsin, suggesting
      blocking of hydrophobic residues. The C-terminal truncation mutant TF389 also
      showed no chaperone activity and could not bind bis-ANS. These results suggest
      that bis-ANS binding may mimic binding of a substrate peptide and that the C
      terminal region of TF plays an important role in hydrophobic binding and
      chaperone function.

PMID- 17525466
TI  - Malonyl-CoA: acyl carrier protein transacylase from Helicobacter pylori: Crystal
      structure and its interaction with acyl carrier protein.
AB  - Malonyl-CoA: acyl carrier protein transacylase (MCAT) is a critical enzyme
      responsible for the transfer of the malonyl moiety to holo-acyl carrier protein
      (ACP) forming the malonyl-ACP intermediates in the initiation step of type II
      fatty acid synthesis (FAS II) in bacteria. MCAT has been considered as an
      attractive drug target in the discovery of antibacterial agents. In this study,
      the crystal structure of MCAT from Helicobacter pylori (Hp) at 2.5 angstroms
      resolution is reported, and the interaction of HpMCAT with HpACP is extensively
      investigated by using computational docking, GST-pull-down, and surface plasmon
      resonance (SPR) technology-based assays. The crystal structure results reveal
      that HpMCAT has a compact folding composed of a large subdomain with a similar
      core as in alpha/beta hydrolases, and a similar ferredoxin-like small subdomain
      as in acylphosphatases. The docking result suggests two positively charged areas
      near the entrance of the active site of HpMCAT as the ACP-binding region. Binding
      assay research shows that HpMCAT demonstrates a moderately binding ability
      against HpACP. The solved 3D structure of HpMCAT is expected to supply useful
      information for the structure-based discovery of novel inhibitors against MCAT,
      and the quantitative study of HpMCAT interaction with HpACP is hoped to give
      helpful hints in the understanding of the detailed catalytic mechanisms for
      HpMCAT.

PMID- 17525467
TI  - Parathyroid hormone is a heparin/polyanion binding protein: binding energetics
      and structure modification.
AB  - The interaction of four representative polyanions with parathyroid hormone (PTH)
      residues 1-84 has been investigated utilizing a variety of spectroscopic and
      calorimetric techniques. Each of the polyanions employed demonstrate
      enthalpically driven binding to PTH (1-84) with significant affinity. The
      polyanions heparin, dextran sulfate, phytic acid, and sucrose octasulfate induce
      alpha-helical structure in PTH to varying extents depending on the ratio of
      polyanion to protein employed. Intrinsic and extrinsic fluorescence spectroscopy
      suggests significant protein tertiary structure alteration upon polyanion
      binding. Although structural modification occurred upon polyanion binding, PTH
      colloidal stability was increased depending on the ratio of polyanion to protein
      used. Nevertheless, the bioactivity of PTH in the presence of various ratios of
      heparin was not altered. The potential biological significance of PTH/polyanion
      interactions is discussed.

PMID- 17525468
TI  - Development of indole chemistry to label tryptophan residues in protein for
      determination of tryptophan surface accessibility.
AB  - Solvent accessibility can be used to evaluate protein structural models, identify
      binding sites, and characterize protein conformational changes. The differential
      modification of amino acids at specific sites enables the accessible surface
      residues to be identified by mass spectrometry. Tryptophan residues within
      proteins can be differentially labeled with halocompounds by a photochemical
      reaction. In this study, tryptophan residues of carbonic anhydrase are reacted
      with chloroform, 2,2,2-trichloroethanol (TCE), 2,2,2-trichloroacetate (TCA), or 3
      bromo-1-propanol (BP) under UV irradiation at 280 nm. The light-driven reactions
      with chloroform, TCE, TCA, and BP attach a formyl, hydroxyethanone, carboxylic
      acid, and propanol group, respectively, onto the indole ring of tryptophan.
      Trypsin and chymotrypsin digests of the modified carbonic anhydrase are used to
      map accessible tryptophan residues using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Tryptophan
      reactivity is determined by identifying peptides with tryptophan residues
      modified with the appropriate label. The reactivity is calculated from the
      frequency that the modification is identified and a semiquantitative measure of
      the amount of products formed. Both of these measures of tryptophan reactivity
      correlate significantly with the accessible surface area of tryptophan residues
      in carbonic anhydrase determined from the X-ray crystal structure. Therefore the
      photochemical reaction of halocompounds with tryptophan residues in carbonic
      anhydrase indicates the degree of solvent accessibility of these residues.

PMID- 17525469
TI  - Similarities in the thermodynamics and kinetics of aggregation of disease-related
      Abeta(1-40) peptides.
AB  - Increasing evidence indicates that polypeptide aggregation often involves a
      nucleation and a growth phase, although the relationship between the factors that
      determine these two phases has not yet been fully clarified. We present here an
      analysis of several mutations at different sites of the Abeta(1-40) peptide,
      including those associated with early onset forms of the Alzheimer's disease,
      which reveals that the effects of specific amino acid substitutions in the
      sequence of this peptide are strongly modulated by their structural context.
      Nevertheless, mutations at different positions perturb in a correlated manner the
      free energies of aggregation as well as the lag times and growth rates. We show
      that these observations can be rationalized in terms of the intrinsic
      propensities for aggregation of the Abeta(1-40) sequence, thus suggesting that,
      in the case of this peptide, the determinants of the thermodynamics and of the
      nucleation and growth of the aggregates have a similar physicochemical basis.

PMID- 17525470
TI  - The disulfide loop of gp41 is critical to the furin recognition site of HIV
      gp160.
AB  - The importance of the HIV gp41 conserved disulfide loop to envelope function has
      been examined by mutational and functional analyses. Based on a luciferase
      reporter entry assay, mutants gp41-CC/AA (C598A/C604A) and gp41-Delta (deletion
      of residues 596-606) result in a nonfunctional envelope protein. Western blot
      analysis shows both mutants to be properly expressed but not processed to form
      gp120 and gp41, which explains their nonfunctionality. The presence of mutant
      gp160 on the cell surface, as well as their ability to bind to sCD4, suggests
      that the mutations have disrupted processing at the furin recognition site
      encoded within the gp120 conserved domain 5, without resulting in an overall
      misfolding of the protein. With respect to the furin recognition site, the
      mutations are sequentially distant, which implies that the gp41 disulfide loop is
      interacting with gp120 C5 in gp160. In addition, we have modeled the gp120-gp41
      interaction in unprocessed precursor gp160 using structural data available for
      gp120 and gp41 domains in isolation, supplemented by mutagenesis data. We suggest
      that the mutations have altered the interaction between gp120 C5 and the gp41
      disulfide loop, resulting in decreased accessibility of the furin recognition
      site and implying that the interaction between the gp120 C5 and gp41 loop is a
      conformational requirement for gp160 processing. The sensitivity of this
      interaction could be exploited in future antivirals designed to disrupt HIV
      pathogenesis by disrupting gp160 processing.

PMID- 17525471
TI  - Rare coding sequence changes are consistent with Ecdysozoa, not Coelomata.
AB  - There is growing interest in the use of alternative, more slowly-evolving RGCs
      (rare genomic changes). Recently, Rogozin and coauthors (Rogozin et al. 2007)
      proposed a novel phylogenetic method employing rare amino acid changes, RGC-CAMs
      (rare genomic changes-conserved amino acids-multiple substitutions). They applied
      their method to 694 sets of eukaryotic orthologs in order to distinguish the
      relationship between nematodes, arthropods and deuterostomes. They concluded that
      such rare amino acid changes were consistent with the Coelomata hypothesis, which
      groups arthropods and deuterostomes to the exclusion of nematodes. Here we use
      newly available genomic sequences from Nematostella vectensis, a basal metazoan,
      and from Brugia malayi, an additional nematode. We show that the apparent support
      for Coelomata is likely to be the result of the rapid rate of evolution leading
      to Caenorhabditis nematodes. Including the additional species paints a very
      different picture, with 13 remaining characters consistent with Ecdysozoa versus
      only 1 consistent with Coelomata.

PMID- 17525472
TI  - Exonic splicing regulatory elements skew synonymous codon usage near intron-exon
      boundaries in mammals.
AB  - In mammals there is a bias in amino acid usage near splice sites that is
      explained, in large part, by the high density of exonic splicing enhancers (ESEs)
      in these regions. Is there a similar bias for the relative use of synonymous
      codons, and can any such bias be predicted by their abundance in ESEs? Prior
      reports suggested that such trends may exist. From analysis of human exons, we
      find that 47 of the 59 codons with at least one synonym show differential usage
      in the proximity of exon ends, of which 42 remain significant after correction
      for multiple testing. Within sets of synonymous codons those more preferred near
      splice sites are generally those that are relatively more abundant within the
      ESEs. However, the examples given previously appear exceptionally good fits and
      there exist many exceptions, the usage of lysine's codons being a case in point.
      Similar results are observed in mouse exons. We conclude that splice regulation
      impacts on the choice of synonymous codons in mammals, but the magnitude of this
      effect is less than might at first have been supposed.

PMID- 17525473
TI  - Protective efficacy of hGSTM1-1 against B[a]P and (+)- or (-)-B[a]P-7,8
      dihydrodiol cytotoxicity, mutagenicity, and macromolecular adducts in V79 cells
      coexpressing hCYP1A1.
AB  - Transgenic cell lines were constructed to study the dynamics of competition
      between activation versus detoxification of benzo[a]pyrene (B[a]P) or B[a]P-7,8
      dihydrodiol metabolites. Stably transfected V79MZ cells expressing human
      cytochrome P4501A1 (hCYP1A1) alone or in combination with human glutathione-S
      transferase M1 (hGSTM1) were used to determine how effectively this GST isozyme
      protects against cytotoxic, genotoxic, and mutagenic effects of B[a]P or the
      enantiomeric dihydrodiol metabolites (+)-benzo[a]pyrene-7,8-dihydrodiol ((+)
      B[a]P-7,8-diol) and (-)-benzo[a]pyrene-7,8-dihydrodiol ((-)-B[a]P-7,8-diol).
      Expression of hGSTM1 in the presence of hCYP1A1 conferred significant 8.5-fold
      protection against B[a]P-induced cytotoxicity, but protection against
      cytotoxicity of either B[a]P-7,8-diol enantiomer was not significant.
      Mutagenicity of B[a]P at the hprt locus was dose and time dependent in cells that
      expressed hCYP1A1. Mutagenicity of B[a]P was reduced by 21-32% and mutagenicity
      induced by the B[a]P-7,8-diols was reduced 20-58% in cells further modified to
      coexpress hGSTM1-1 compared to cells expressing hCYP1A1 alone. Expression of
      hGSTM1-1 reduced adducts in total cellular macromolecules by twofold, in good
      correlation with the reduction in B[a]P mutagenicity. These results indicate that
      while hGSTM1-1 effectively protects against hCYP1A1-mediated cytotoxicity of
      B[a]P, a significant fraction of the mutagenicity that results from activation of
      B[a]P and its 7,8-dihydrodiol metabolites by hCYP1A1 is derived from B[a]P
      metabolites that are not detoxified by hGSTM1.

PMID- 17525474
TI  - Cellular palmitoylation and trafficking of lipidated peptides.
AB  - Many important signaling proteins require the posttranslational addition of fatty
      acid chains for their proper subcellular localization and function. One such
      modification is the addition of palmitoyl moieties by enzymes known as palmitoyl
      acyltransferases (PATs). Substrates for PATs include C-terminally farnesylated
      proteins, such as H- and N-Ras, as well as N-terminally myristoylated proteins,
      such as many Src-related tyrosine kinases. The molecular and biochemical
      characterization of PATs has been hindered by difficulties in developing
      effective methods for the analysis of PAT activity. In this study, we describe
      the use of cell-permeable, fluorescently labeled lipidated peptides that mimic
      the PAT recognition domains of farnesylated and myristoylated proteins. These PAT
      substrate mimetics are accumulated by SKOV3 cells in a saturable and time
      dependent manner. Although both peptides are rapidly palmitoylated, the SKOV3
      cells have a greater capacity to palmitoylate the myristoylated peptide than the
      farnesylated peptide. Confocal microscopy indicated that the palmitoylated
      peptides colocalized with Golgi and plasma membrane markers, whereas the
      corresponding nonpalmitoylatable peptides accumulated in the Golgi but did not
      traffic to the plasma membrane. Overall, these studies indicate that the
      lipidated peptides provide useful cellular probes for quantitative and
      compartmentalization studies of protein palmitoylation in intact cells.

PMID- 17525475
TI  - The pathologies associated with functional titration of phosphatidylinositol
      transfer protein alpha activity in mice.
AB  - Phosphatidylinositol transfer proteins (PITPs) bind phosphatidylinositol (PtdIns)
      and phosphatidylcholine and play diverse roles in coordinating lipid
      metabolism/signaling with intracellular functions. The underlying mechanisms
      remain unclear. Genetic ablation of PITPalpha in mice results in neonatal
      lethality characterized by intestinal and hepatic steatosis, spinocerebellar
      neurodegeneration, and glucose homeostatic defects. We report that mice
      expressing a PITPalpha selectively ablated for PtdIns binding activity
      (Pitpalpha(T59D)), as the sole source of PITPalpha, exhibit phenotypes that
      recapitulate those of authentic PITPalpha nullizygotes. Analyses of mice with
      graded reductions in PITPalpha activity reveal proportionately graded reductions
      in lifespan, demonstrate that intestinal steatosis and hypoglycemia are apparent
      only when PITPalpha protein levels are strongly reduced (>or=90%), and correlate
      steatotic and glucose homeostatic defects with cerebellar inflammatory disease.
      Finally, reconstitution of PITPalpha expression in the small intestine
      substantially corrects the chylomicron retention disease and cerebellar
      inflammation of Pitpalpha(0/0) neonates, but does not rescue neonatal lethality
      in these animals. These data demonstrate that PtdIns binding is an essential
      functional property of PITPalpha in vivo, and suggest a causal linkage between
      defects in lipid transport and glucose homeostasis and cerebellar inflammatory
      disease. Finally, the data also demonstrate intrinsic neuronal deficits in
      PITPalpha-deficient mice that are independent of intestinal lipid transport
      defects and hypoglycemia.

PMID- 17525476
TI  - Fenofibrate increases HDL-cholesterol by reducing cholesteryl ester transfer
      protein expression.
AB  - In addition to efficiently decreasing VLDL-triglycerides (TGs), fenofibrate
      increases HDL-cholesterol levels in humans. We investigated whether the
      fenofibrate-induced increase in HDL-cholesterol is dependent on the expression of
      the cholesteryl ester transfer protein (CETP). To this end, APOE*3-Leiden (E3L)
      transgenic mice without and with the human CETP transgene, under the control of
      its natural regulatory flanking regions, were fed a Western-type diet with or
      without fenofibrate. Fenofibrate (0.04% in the diet) decreased plasma TG in E3L
      and E3L.CETP mice (-59% and -60%; P < 0.001), caused by a strong reduction in
      VLDL. Whereas fenofibrate did not affect HDL-cholesterol in E3L mice, fenofibrate
      dose-dependently increased HDL-cholesterol in E3L.CETP mice (up to +91%).
      Fenofibrate did not affect the turnover of HDL-cholesteryl ester (CE), indicating
      that fenofibrate causes a higher steady-state HDL-cholesterol level without
      altering the HDL-cholesterol flux through plasma. Analysis of the hepatic gene
      expression profile showed that fenofibrate did not differentially affect the main
      players in HDL metabolism in E3L.CETP mice compared with E3L mice. However, in
      E3L.CETP mice, fenofibrate reduced hepatic CETP mRNA (-72%; P < 0.01) as well as
      the CE transfer activity in plasma (-73%; P < 0.01). We conclude that fenofibrate
      increases HDL-cholesterol by reducing the CETP-dependent transfer of cholesterol
      from HDL to (V)LDL, as related to lower hepatic CETP expression and a reduced
      plasma (V)LDL pool.

PMID- 17525477
TI  - Hydrophobic ligand binding properties of the human lipocalin apolipoprotein M.
AB  - Apolipoprotein M (apoM) is a plasma protein associated mainly with HDL. ApoM is
      suggested to be important for the formation of prebeta-HDL, but its mechanism of
      action is unknown. Homology modeling has suggested apoM to be a lipocalin.
      Lipocalins share a structurally conserved beta-barrel, which in many lipocalins
      bind hydrophobic ligands. The aim of this study was to test the ability of apoM
      to bind different hydrophobic substances. ApoM was produced both in Escherichia
      coli and in HEK 293 cells. Characterization of both variants with electrophoretic
      and immunological methods suggested apoM from E. coli to be correctly folded.
      Intrinsic tryptophan fluorescence of both apoM variants revealed that retinol,
      all-trans-retinoic acid, and 9-cis-retinoic acid bound (dissociation constant = 2
      3 microM), whereas other tested substances (e.g., cholesterol, vitamin K, and
      arachidonic acid) did not. The intrinsic fluorescence of two apoM mutants
      carrying single tryptophans was quenched by retinol and retinoic acid to the same
      extent as wild-type apoM, indicating that the environment of both tryptophans was
      affected by the binding. In conclusion, the binding of retinol and retinoic acid
      supports the hypothesis that apoM is a lipocalin. The physiological relevance of
      this binding has yet to be elucidated.

PMID- 17525478
TI  - Radiation-induced thyroid cancer: what we have learned from chernobyl.
AB  - An increased incidence of thyroid cancer in the exposed children remains the most
      well-documented long-term effect of radioactive contamination after the Chernobyl
      nuclear accident in April, 1986. Multiple studies on approx 4000 children and
      adolescents with thyroid cancer have provided important new information about the
      epidemiological, clinical, pathological, and molecular aspects of radiation
      induced carcinogenesis in the thyroid gland. They revealed that environmental
      exposure to 131I during childhood carries an increased risk of thyroid cancer and
      the risk is radiation dose dependent. The youngest children are most sensitive to
      radiation-induced carcinogenesis, and the minimal latent period for thyroid
      cancer development after exposure is as short as 4 yr. The vast majority of these
      cancers are papillary carcinomas, many of which have characteristic solid or
      solid-follicular microscopic appearance. On the molecular level, post-Chernobyl
      tumors are characterized by frequent occurrence of chromosomal rearrangements,
      such as RET/PTC, whereas point mutations of BRAF and other genes are much less
      common in this population.

PMID- 17525480
TI  - Molecular and cellular biology of pheochromocytomas and extra-adrenal
      paragangliomas.
AB  - Efforts to understand the pathobiology of pheochromocytomas and extra-adrenal
      paragangliomas have been spurred by genetic and gene expression profiling studies
      showing genotype-phenotype correlations in familial
      pheochromocytoma/paraganglioma syndromes and in some sporadic tumors. The current
      challenge is to relate catalogs of genetic and phenotypic markers to cell
      biology. Hypothetical bases for genotype-phenotype correlations include: cell of
      origin, pathway dependence, and functional and anatomic context. A further
      consideration is phenotype plasticity. Cross talk between signaling pathways
      provides a general framework for understanding how mutations of apparently
      unrelated genes might lead to the same type of tumor, and also suggests that
      targeted therapies might be directed either at a specific mutated gene or a
      downstream signal transducer. However, precise mechanisms of tumorigenesis remain
      unknown. An intriguing hypothesis proposes that mutations of RET, NF1, VHL, or
      SDH predispose to hereditary pheochromocytoma/ paraganglioma by causing defective
      apoptotic culling of cells that would normally be destroyed during embryogenesis.
      An argument favoring survival rather than mitogenesis as a common denominator is
      that the same mutations are rare in sporadic pheochromocytomas/paragangliomas,
      suggesting they only need to act during a limited developmental window. An
      implication is that tumor precursors could be identified and eradicated in
      individuals who carry the mutations.

PMID- 17525481
TI  - Histopathology and immunohistochemistry of adrenal medullary tumors and
      paragangliomas.
AB  - Paragangliomas arise from sympathetic or parasympathetic paraganglia and should
      now be defined by their site and type. The term pheochromocytoma is reserved for
      intra-adrenal tumors. This short review discusses the gross and microscopic
      features, the immunohistochemical profile, the problem of recognizing malignant
      potential, and the rare instances where a differential diagnosis has to be
      considered.

PMID- 17525482
TI  - Familial pheochromocytomas and paragangliomas: stories from the sign-out room.
AB  - In this overview we present five patients with apparently sporadic
      pheochromocytomas or paragangliomas which turned out to be associated with an
      inheritable familial disease. For each patient a family history together with
      clinical, morphological, as well as molecular data are reported. The identified
      syndromes include multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau
      syndrome (VHL), neurofibromatosis type 1 (NF1), and familial
      pheochromocytoma/paraganglioma syndrome (SDHx). A brief summary of phenotypes,
      the genes involved, and typical mutations in these syndromes is provided.

PMID- 17525483
TI  - Recent advances in histopathology and immunohistochemistry of adrenocortical
      carcinoma.
AB  - Discerning malignancy in resected adrenocortical neoplasms can pose diagnostic
      difficulty. Macroscopic examination is the first important step toward diagnosis
      and should include accurate measurement of weight and dimension of the specimens
      and description of the cut surface of the tumors. It is also important to sample
      the specimens for histological diagnosis near foci of hemorrhage and/or necrosis.
      Histological scoring systems evaluating multiple parameters, especially the
      criteria of Weiss, have been shown to be reliable in differential diagnosis
      between adrenocortical adenoma and carcinoma. A tumor is defined as
      adrenocortical carcinoma when three or more of the following criteria are met;
      (1) high nuclear grade, (2) mitotic rate six or more per 50 high power fields,
      (3) atypical mitosis, (4) clear cells less than 25%, (5) a diffuse architecture
      pattern in more than one-third of the tumor, (6) confluent necrosis, (7) venous
      invasion, (8) sinusoidal invasion, and (9) capsular invasion. The criteria are
      relatively straightforward and considered the most effective standard for
      diagnosis of adrenocortical malignancy. However, great care should be taken in
      applying the criteria to histological evaluation of two relatively rare and
      peculiar adrenocortical tumors, adrenocortical oncocytoma and pediatric
      adrenocortical neoplasms. At this juncture, ancillary biological or molecular
      markers are of little practical value in terms of differential diagnosis between
      adrenocortical adenoma and carcinoma but tumors with MIB1 or Ki-67 labeling index
      more than 2.5 may be considered malignant. Prognostic markers of adrenocortical
      carcinoma have not been established other than complete respectability of the
      tumor. There are also no surrogate markers for predicting response to therapy
      with Mitotane, an adrenolytic agent. It sometimes is important for surgical
      pathologists to differentiate adrenocortical carcinoma from metastatic
      malignancies of other sites. An immunohistochemical evaluation of adrenal 4
      binding protein (Ad4BP) or SF-1, a transcription factor of all steroidogenesis,
      can aid in this differential diagnosis because nuclear immunoreactivity for this
      transcription factor is relatively specific to steroid producing cells.

PMID- 17525484
TI  - Molecular pathology of adrenal cortical tumors: separating adenomas from
      carcinomas.
AB  - Adrenal cortical carcinoma is a rare but interesting endocrine tumor. Its
      diagnosis is usually straightforward using morphologic assessment and
      supplemental immunohistochemistry. However, diagnostically challenging cases
      exist and pathologic evaluation would benefit from the availability of adjunctive
      molecular testing. Here, the relevant molecular pathology of adrenal cortical
      tumors is reviewed with special reference to those methods (e.g., DNA
      microarrays) that hold promise for improved diagnosis and prognosis, and
      prediction of therapeutic response.

PMID- 17525485
TI  - Cytokeratin CK20 is a sensitive marker for Crooke's cells and the early
      cytoskeletal changes associated with hypercortisolism within pituitary
      corticotrophs.
AB  - Crooke's cells are nonneoplastic corticotroph cells found in the adenohypophysis
      of patients who have an endogenous or exogenous excess of glucocorticoids.
      Classic Crooke's cells have a prominent hyaline cytoplasmic ring that displaces
      the basophilic granules of the normal cell. This characteristic appearance is
      produced by a perinuclear accumulation of cytokeratin filaments.
      Immunohistochemistry for cytokeratins is a sensitive way to identify Crooke's
      cells, but a keratin antibody specific for Crooke's hyaline change has not been
      reported. Normal pituitary epithelial cells are variably reactive for many
      keratin antibodies but are negative for cytokeratin 20 (CK20) expression. We
      evaluated the use of CK20 immunohistochemistry as a marker for Crooke's cells. We
      examined sections from 25 pituitary glands resected from 15 patients who had
      undergone exogenous glucocorticoid administration and from 10 patients with an
      endogenous source of hypercortisolism; sections from 10 normal pituitary glands
      obtained at autopsy were used as controls. CK20 immunoreactivity was observed
      only in corticotrophs. A staining pattern consistent with classic Crooke's cells
      was seen in pituitary gland sections from 15 of the cases. Cells with less
      intense CK20 positivity were present in sections from all 25 cases. We found CK20
      to be a sensitive and specific marker for Crooke's cells and also for the
      previously unrecognized, subtle, cytoskeletal changes that occur in corticotrophs
      in response to hypercortisolism.

PMID- 17525486
TI  - Expression of prolactin receptor and prolactin in normal and malignant thyroid: a
      tissue microarray study.
AB  - OBJECTIVE: There is increasing evidence involving prolactin (PRL) and its
      receptor (PRLR) in the development of different cancers. The aim of the present
      study was to investigate the expression of PRLR and PRL in human thyroid tissues.
      DESIGN AND METHODS: Using tissue microarray (TMA) by immunohistochemical
      staining, we examined the expression level of PRLR and PRL in 314 specimens from
      71 thyroid cancer patients and 15 normal thyroid samples. RESULTS: Expression of
      the PRLR was observed in 93.3% of normal thyroid samples and in 76.1% of all
      thyroid cancers, while expression of PRL was observed in only 10% of medullary
      thyroid carcinomas and not at all in the other specimens, whether normal or
      neoplastic. Moreover, results suggested an overexpression of PRLR in 70% of
      medullary thyroid carcinomas, whereas 53.3% of poorly differentiated thyroid
      carcinomas showed a negative pattern of staining (p = 0.014 vs normal).
      CONCLUSIONS: Present data revealed, for the first time, a widespread expression
      of PRLR in normal and neoplastic human thyroid tissues as well as a scarce
      expression of PRL, observed only in a few medullary thyroid carcinomas. Whether
      the overexpression of PRLR observed in medullary thyroid carcinomas or the
      underexpression of PRLR observed in poorly differentiated thyroid carcinomas play
      a contributory role in the oncogenesis of these tumors remains to be determined.

PMID- 17525487
TI  - Differential expression of human telomerase catalytic subunit mRNA by in situ
      hybridization in pheochromocytomas.
AB  - In pheochromocytomas, it is very difficult to predict malignant potential by
      conventional histology or immunohistochemical and molecular markers. We
      investigated the expression of human telomerase catalytic component (hTERT) mRNA,
      hTERT protein, Ki-67 antigen, and p27kip1 in pheochromocytomas (27 benign, 7
      suspected malignant, and 7 malignant), and evaluated the possibility of
      expressions of these proteins, and hTERT mRNA serve as diagnostic markers for
      predicting the biological behavior of these tumors. All tumors showed the
      classical histology and typical immunohistochemical pattern. By in situ
      hybridization, hTERT mRNA was expressed in 5/7 malignant tumors (defined as the
      presence of metastasis and/or extensive local invasion) as compared with 3/27
      benign tumors. We examined the hTERT by immunohistochemistry to confirm the mRNA.
      hTERT mRNA expression was correlated with hTERT protein expression. All benign
      tumors exhibited no immunopositivity or <1% of cells stained for Ki-67 antigen.
      Six out of seven malignant tumors have shown either hTERT mRNA expression or Ki
      67 immunoreactivity. While no statistical difference in p27kip1 expressions was
      observed among benign, malignant, and suspected malignant tumors, there was a
      statistical difference between the normal adrenal medulla samples and tumors (p <
      0.001). Thus, hTERT mRNA detection by in situ hybridization, hTERT expression,
      and Ki-67 antigen expression are all useful tools for differentiating malignant
      from benign pheochromocytomas.

PMID- 17525488
TI  - Poorly differentiated thyroid carcinoma with rhabdoid phenotype: a diagnostic
      dilemma--report of a rare case.
AB  - Rhabdoid tumor is a distinct entity reported in renal and extrarenal sites.
      Malignant tumors of various types may have rhabdoid phenotype. There are eight
      case reports of carcinomas of thyroid with rhabdoid phenotype. All of these
      cases, except two, have been reported in middle-aged women (42-72 yr) and have
      had an aggressive clinical course with death occurring within few months to 4 yr
      after diagnosis. We report a case of poorly differentiated carcinoma of the
      thyroid with rhabdoid phenotype in a 22-yr-old male. The rhabdoid cells were
      immunopositive for thyroid transcription factor-1, vimentin, epithelial membrane
      antigen, and focally for cytokeratin. Synaptophysin, chromogranin, thyroglobulin,
      carcinoembryonic antigen, smooth muscle actin, myogenin, and desmin were all
      negative. To the best of our knowledge this is the ninth case report of carcinoma
      of the thyroid with rhabdoid phenotype. This case, unlike the previous reported
      cases, has certain unusual features including presentation in a young male, the
      absence of either follicular/papillary differentiation, and immunohistochemical
      profile of the rhabdoid cells.

PMID- 17525489
TI  - [Theory and practice of low-flow anaesthesia].
AB  - The article depicts the history of inhalation anesthesia and closed system
      anesthesia. Closed or almost closed anesthesia systems have been in use since
      1850. At that time, the anesthetic agent was chloroform. It was administered via
      a closed system, where potassium hydroxide was utilized as a carbon dioxide
      scavenger. However, that kind of CO2 absorption method did not gain acceptance.
      Later, a quick and effective method of carbon dioxide absorption was developed
      when the first soda-lime absorber was introduced in 1917. In the mid 1950's, when
      halothane was brought forth, the use of low-flow and closed circle system
      anesthesia diminished significantly. This was largely due to the inherent problem
      in the first generation halothane vaporizers, which was the unreliable delivery
      of vapor at low fresh gas flows. Introduction of isoflurane in the early 1980's,
      gave way to a renewed interest in low flow and closed circuit anesthesia. It was
      further enhanced by the fact that anesthetic agents are atmospheric pollutants,
      especially nitrous oxide, halothane, enflurane, and to some extent isoflurane.
      The introduction of new low solubility agents, like desflurane and sevoflurane,
      have initiated a renaissance in the use of low-flow anesthesia, in order to
      contain costs associated with adapting fresh gas flows to patient demand.

PMID- 17525490
TI  - [Transvaginal ultra sonography in atypical hyperplasia and early cancer of
      endometrium (diagnostic significance and prognostic evaluation)].
AB  - The aim of the article was determination of diagnostic significance and
      prognostic evaluation of transvaginal ultra sonography ( TV US) in atypical
      hyperplasia and early stage of endometrium cancer a complex examination of 58
      different age women was carried out. The examination revealed negative prognostic
      value of endometrial thickness from 12 to 14 mm in reproductive and
      perimenopausal periods; and endometrial thickness from 9 mm to 12 mm in
      menopausal period. Endometrial thickness more than 19 mm is pathognomic for early
      stage of endometrium cancer. The comparative assessment of TV US prognostic
      evaluation and hysteroscopy showed relatively high frequency of false-negative
      results obtained by using TV US (14,3% vs. 5,5%).

PMID- 17525491
TI  - [Pathogenetic correction of reproductive function disorder in patients with
      normogonadotropic ovary deficiency caused by body mass deficiency].
AB  - The aim of the article was the recovery of fertility and realization of
      reproductive function of women with body mass deficiency (BMD). Thirty seven
      patients with normogonadotropic ovary deficiency caused by body mass deficiency
      (12-15% of normal value) underwent pathogenetic treatment, starting from the
      disorder of hypothalamic-hypophyseal-ovarian system. Pathogenetic therapy was
      directed to compensate body mass deficit. Hormonal replacement therapy aimed to
      restore the negative feedback. Compensation of body mass (5-7%) increases the
      efficiency of hormonal replacement therapy by 16% on average, while the total
      compensation of the deficiency is manifested in 68% cases of recovery. As a
      result of therapy, seven women with BMD restored fertility and realized their
      reproductive function.

PMID- 17525492
TI  - [Hormonal contraception and cervix of the uterus pathology].
AB  - The effect of hormonal contraception on cervix of the uterus of young nullipara
      women with ectopia was investigated. Cohort study was carried out by using simple
      blind method. By means of statistical data manipulation correlation between the
      application of hormonal contraceptives and changes of colposcopy pictures in the
      zone of pathology was displayed. Excluton showed low percent anomalous colpscopy
      picture in pathology zone. Excluton was declared as medicine of choice for
      nullipara women with ectopia. Still it is necessary to conduct a strong dynamic
      control of cervix of the uterus (colposcopy and pap-smear test) in order to avoid
      complications.

PMID- 17525493
TI  - [Diagnostics of stress-incontinence in women].
AB  - In experimental model, imitating lower urinary tract was detected the
      significance of urodinamic researches for diagnostic of stress incontinence. We
      suggested math formules for determine opening and closing of sphincter and their
      connection to the bladder volume, on the basis of uroflowgrame analysies, where
      was noted the uncontroled leakege of liquid (urine). By cystometry was detected
      the connection between opening of urethral sphincter and the pressure of the
      bladder, when was determined the stress incontinence. It was concluded that
      urodinamic figures have significant diagnostical value at stress incontinence and
      could help in choosing conservative treatment or surgery.

PMID- 17525494
TI  - Treatment of aggressive non-Hodgkin's lymphomas.
AB  - The aim of the study was to evaluate overall survival in patients with diagnosis
      DLBCL, comparing CHOP chemotherapy plus rituximab with CHOP alone, and standard
      plus intensive regimens (BEAM). Above mentioned regimens were compared in high
      risk patient, who were identified according to the CD10 expression with factors
      of IPI. 27 patients with diagnosis of diffuse large B-cell lymphomas were under
      observation. CD20 expression was assessed in all cases. Overall survival therapy
      was compared in three groups. I- primary refractory patients who undergone
      chemotherapy with CHOP regimen (9 patents); II - patients refractory to the
      standard added intensive chemotherapy regimens (BEAM) (10 patients). III -
      patients who were treated with combination CHOP plus rituximab (8 patients); As
      it shown on the figure overall survival was the highest in III group and composes
      17 months, as for II and I groups overall survival was 7,4 and 8,8 months
      respectively. In summary based on our observations quantity of unfavorable
      prognostic factors may determine primary refractory patients to standard
      therapies and first line treatment in CD20 positive cases with CHOP plus
      Rituximab regimen increased overall survival from 7,4 month to 17 month (p<0,01).

PMID- 17525495
TI  - [Diagnostic value of the procalcitonine test in purulent-septic complications of
      chest traumas].
AB  - The aim of the present work was to assess the value of the semi-quantitative
      procalcitonine test (PCT) in diagnosis of purulent-septic complications of chest
      traumas, efficacy of the therapy carried out, and outcome prognosis. For this, 71
      patients with chest traumas were enrolled in the study. Concentrations of PCT
      were assessed in dynamics using an immunochromatographic, semi-quantitative quick
      test. Semi-quantitative quick PCT test is highly sensitive diagnostic marker that
      can be used for the assessment of a chest trauma, infectious-septic complication
      severity, and efficiency of the therapy indicated. Thus, it can be successfully
      used for monitoring trauma therapy. PCT sensitivity during first 12 hrs of
      infectious-septic complication development is 2-3-times higher than that of
      routine methods for laboratory diagnostics, and even more sensitive that IL-6 and
      CRT, when we are dealing with combined chest traumas. PCT concentration increase
      is 4-times more frequent in gram-positive bacterial processes than in gram
      negative ones. This has to be taken into account, when appropriate antibacterial
      treatment is selected for restricted infectious-septic complications.

PMID- 17525496
TI  - [Estimation of effectiveness of peroral mucolytic agents in treatment of
      inflammatory diseases of middle ear and paranasal sinusitis].
AB  - The aim of the work was estimation of perolar mucolytic agents in treatment of
      inflammatory diseases of middle ear and paranasal sinusitis. On the basis of
      research it was concluded that Sinupret reduced the necessity of grommet.
      Sinupret is the best systemic mucolytic in the treatment of inflammatory disease
      of middle ear and paranasal sinuses. To treat seros otitis media Sinupret was
      used as a monotherapy drug. In treatment of acute otitis media and sinusitis
      Sinupret is recommended in the third period of disease in combination with
      antibiotics.

PMID- 17525497
TI  - [Antibacterial nature of medicinal ointments, based on Georgian mineral waters in
      treatment of generalized periodontitis].
AB  - The goal of the work was to determine antibacterial nature of the medicinal
      ointments (N1 - "Achtala"; N2 - "Sairme", N3 - "Tschaltubo", N4 "Amagleba") based
      on Georgian mineral waters and containing bio-active extracts. The goal of the
      work was to determine antibacterial nature of the medicinal ointments (N1 -
      "Achtala"; N2 - "Sairme", N3 - "Tschaltubo", N4 "Amagleba") based on Georgian
      mineral waters and containing bio-active extracts. The investigation was done in
      purpose to determine microbial structure of oral cavity of the 80 patients with
      chronic generalized periodontitis, as a result was confirmed, that microbial
      structure of these patients was rather heterogeneous and is presented by
      different aerobe, microaerophil and anaerobe microbial flora. The sensitivity,
      resistance, of isolated microorganisms, was studied to modern groups of
      antibiotics. Results of investigations are: high antibacterial activities of
      ointments, prepared on mineral waters of Georgia. So, it can be recommended for
      usage in treatment schedule for patients with chronic generalized periodontitis.

PMID- 17525498
TI  - [Dynamics of echocardiographic changes and the tactic of optimal therapy in
      patients with atrial fibrillation with chronical heart failure].
AB  - The aim of the article was to assess the efficacy of treatment of atrial
      fibrillation (AE) and congestive heart failure (CHF) with Enalapril in
      combination with Cordaron. For this reason 62 patients from 37 to 70 years old
      (mean age 54, 6 +/- 6,1) with CHF (class II-III NYHA) and persistent AF underwent
      the medical treatment. The suggested scheme of treatment improved HF functional
      class by NYHA, raised anti reactive effectiveness and favorably influenced on the
      diastolic function of the LV in this type of patients.

PMID- 17525499
TI  - [Effectiveness of treatment and prophylactic methods in persons with ischemic
      heart disease risk factors].
AB  - The article investigates the effectiveness of prophylactic measures in persons
      with risk factors of coronary arterial disease (RF CAD). For this reason
      unorganized population (aged 30-59) was examined and CAD was diagnosed by
      standard means of epidemiologic methods. The persons with RF were revealed.
      Functional state of hemostasis system, as well as definition of total blood
      cholesterol level was performed by two brevity screening systems of investigation
      (initial and second-screening systems). Seven years of prospective research
      proved the effectiveness of proposed prophylactic methods in men and women with
      CAD RF. Complex prophylactic treatment considerably reduced the possibility of
      development CAD and stroke, mortality.

PMID- 17525500
TI  - [Peculiarities of postprandial activity of lipoprotein lipase in coronary heart
      disease].
AB  - The aim of investigation was to study the peculiarities of activity of
      lipoprotein lipase (LPL) and serum lipid spectrum after fat test meal in patients
      with coronary heart disease (CHD). 42 persons have been investigated. The main
      group consisted of 27 patients with CHD (13 males, 14 females). 15 almost healthy
      subjects (5 males, 10 females) were unified in control group. Parameters of lipid
      metabolism have been studied by biochemical technique both in basal state and at
      3 hours after standard test meal. In parallel, the levels of LPL activity have
      been investigated by potentiometric method. The values of LPL activity in
      patients with CHD both in basal and in postprandial states were significantly
      lower in comparison with analogous values of control subjects. Its postprandial
      level in CHD patients did not change significantly (percentage increment was
      1,0+/-0,9%), but in control group - was increased by 22,3+/-4,4%. Obtained
      results suggest that LPL activity is not increased at increased postprandial
      atherogenic lipemia in patients with CHD. LPL activity should be considered as a
      metabolic marker of atherogenesis and CHD.

PMID- 17525501
TI  - Effect of metformin therapy on plasma adiponectin and leptin levels in obese and
      insulin resistant postmenopausal females with type 2 diabetes.
AB  - To investigate the relative role of the adiponectin and leptin in the insulin
      resistance (IR) and obesity we studied plasma levels of these adipocytokines in
      obese and insulin resistant postmenopausal (PM) females with type 2 diabetes
      (DM2) during 6 months of Metformin therapy. We recruited 26 PM women, between the
      ages of 50 and 67 (59,7+/-8,1 years). These women had a BMI of 36,6+/-1,8 kg/m2.
      After baseline measurements Metformin therapy has been initiated (1700+/-2550 mg
      per day). Duration of therapy was 6 months. The results of investigations of
      adipocytokines after Metformin 6 months therapy shown that circulating
      adiponectin levels were significantly increased (19,1+/-6,0 vs. 16,1+/-3,9 ng/ml,
      p=0,008) together with significant reduction of BMI (35,9+/-1,9 vs. 36,6+/-1,8
      kg/m2, p=0,005) and IR (3,05+/-0,89 vs. 3,96+/-0,70, p<0,001). The magnitude of
      the change in adiponectin levels positively correlated with the magnitude of BMI
      reduction (r=0,4784, p=0,013) and IR reduction (r=0,5779, p=0,002). Any
      significant correlation did not observed between changes of leptin levels and
      BMI, leptin levels and IR. In summary, our data suggest that hypoadiponectinemia
      in PM may be explained by only IR because the amelioration of whole-body insulin
      action by 6-month Metformin therapy leads to increase of plasma adiponectin
      levels; leptin levels did not significantly change after 6-month Metformin
      therapy.

PMID- 17525502
TI  - [The status of redox system in patients with chronic autoimmune thyroiditis].
AB  - The aim of present investigation was to study redox processes and to establish
      state of blood oxidative and antioxidant systems in patients with chronic
      autoimmune thyroiditis (CAT). 19 patients with CAT (2 males, 17 females; mean age
      35,3+/-14,8 years) have been randomly investigated, of which 3 patients (15,8%)
      had hypothyroidism, 11 (57,9%) - euthyroidism and 5 (26,3%) - hyperthyroidism.
      Control group consisted of 10 practically healthy subjects (2 males, 8 females;
      mean age 41,1+/-11,7 years). The parameters of blood redox-system were
      investigated by electron-paramagnetic resonance method (EPR). The value of
      ceruloplasmin in patients with CAT was significantly higher than in control group
      (20,0+/-2,0 mm/mg vs. 16,0+/-1,1 mm/mg, p<0,001); EPR-signal of Fe3+ -
      transferrin in main group was also significantly higher (18,5+/-1,3 mm/mg vs.
      22,0+/-0,9 mm/mg, p<0,001); values of nitric oxide in both groups were almost
      identical. EPR-signals of methemoglobin significantly correlated with thyroid
      volume (r=0,5421, p=0,016). These changes demonstrate possible relationship
      between CAT and blood redox system. It should be supposed that the introduction
      of antioxidant preparations will improve CAT pathogenetic therapy.

PMID- 17525503
TI  - [The role of endothelial dysfunction and Chlamydia pneumoniae infection in
      patients with ischemic stroke].
AB  - The research purposed to investigate the Chlamydia Pneumoniae infection in
      patients with ischemic stroke and to establish the correlation with elevated C.
      pneumonia antibody titers and endothelial dysfunction. 72 patients with acute
      ischemic stroke, aged 45 to 75 (45 male and 32 female) have been researched.
      Patients were grouped according to etiology of stroke (based on International
      classification TOAST). The blood was taken in 48 hours from stroke onset. ELISA
      method was applied to detect the antibodies against C. Pneumoniae. The intima
      media thickness of the common carotid artery were assessed by B-mode
      ultrasonography (Acuson128XP/10) with a 7.5-MHz linear-array transducer. Flow
      mediated dilatation (FMD) of the brachial artery were measured from high
      resolution, 2-dimensional ultrasound images obtained by an ultrasound machine
      with a 7.5-MHz linear-array transducer. Free NO were examined by Electron
      Paramagnetic Resonance (EPR) method in blood. Control consisted with 15 healthy
      volunteers. Multivariate logistic regression showed a significant positive
      correlation between blood elevated titers of IgA and IgG of stroke patients and
      the intima-media thickness of the carotid artery (correlation coefficient by
      Pearson r = 0,31; p<0,05, r = 0,27; p<0,05). On multiple regression analysis,
      percent FMD showed a significant negative correlation with the intima-media
      thickness of the common carotid artery (r= -0,57, p<0,05), positive correlation
      between NO and the intima-media thickness of the carotid artery (r= 0,72,
      p<0,05). Association between antibody seropositivity for C. pneumoniae and
      increase of the IMT in the common carotid artery indicates persistent chronic
      infection in patients with ischemic stroke. Correlation between NO, an increase
      of the IMT in the common carotid and artery flow-mediated dilation of brachial
      artery indicates on the participation of NO in development of endothelial
      dysfunction and its significant role in pathogenesis of ischemic stroke. These
      findings support the concept that NO-inducible endothelial dysfunction is related
      to atherogenesis.

PMID- 17525504
TI  - [Effectiveness of the treatment plan for androgenetic alopecia].
AB  - The genetic background and some environmental factors have been reported as cause
      of hair growth disturbances. The damage of the biological rhythm of hair growth
      causes the decrease of length of phase and stunted hair growth, leading to
      diffuse alopecia. The scheme of hair loss treatment, by means of preparations
      affecting pathogenetical mechanisms of diffuse hair loss development is offered.
      The clinical evaluation of hair post treatment condition is given as well. The
      clinical study has shown high therapeutic efficacy of proposed scheme for
      treatment of patients, suffer from "acute, chronic diffuse hair loss",
      androgenetical alopecia. Authors conclude that proposed scheme allows obtaining
      marked results.

PMID- 17525505
TI  - [Resuscitational aspects of evolution of history of death teaching and
      interpretation of concept of death as bioethical category].
AB  - The aim of the research was to determine the role of resuscitation science and
      practice in development of new trends in thanatology; and to determine the
      significance of integrated interdisciplinary approach to notion "death" as
      "biological, medical, and bioethical" categories. The author discusses nine
      distinct concepts of death and concludes that only complex scientific approach
      can enrich the knowledge about the notion of death. The list of different aspects
      of interdisciplinary bioethical definition of notion "death" was developed.

PMID- 17525506
TI  - [Autoregulation of cerebral blood flow in condition of experimental hepatic
      encephalopathy].
AB  - The linear interrelation between Systemic Arterial Blood Pressure and local
      Cerebral Blood Flow has been shown in experiments on rats with induced
      experimental hepatic encephalopathy. This is evidence of complete malfunctioning
      of the mechanism of Cerebral Blood Flow Autoregulation. Quantitative comparison
      of local Cerebral Blood Flow intensity in control and experimental (Hepatic
      Encephalopathy) animals has shown significant increase of the basic level of
      cerebral blood flow in rats with induced Hepatic Encephalopathy (p<0,05). On the
      basis of own and literature data the chain of developments in experimental
      hepatic encephalopathy was drawn: excess of Nitric Oxide because of hepatic
      failure can cause the cerebral vasodilatation with inadequate increase of
      cerebral blood flow intensity, resulting in malfunction of the cerebral blood
      flow autoregulation, increase of Blood Brain Barrier permeability, and
      penetration of toxic substances in nervous tissue. As a result of these-
      cognitive deficiency is developed (at the best) and hepatic coma (at the worst).

PMID- 17525507
TI  - [Morphological correlate of newborns peripheral blood cells with activity of
      maternal cytomegalovirus infection].
AB  - Peripheral blood cells specimens were analyzed electron microscopically in 14
      newborns with congenital CMV infection (I group) and in 11 newborns with sub
      clinical form of CMV infection (II group) to correlate the ultra structural
      features of the neonates' blood cells with the maternal CMV activity in active
      primary and reactivated latent CMV infection forms. Control - 20 healthy
      newborns. The groups were arranged according the data of immune testing on IgM
      and IgG antibodies using ELIZA method. Criteria for cases were: 1) neonatal death
      and 2) severe respiratory distress or central nervous system-related symptoms at
      birth. In group I ultra structural findings of basophiles and lymphocytes
      indicate on severe damages of cells related to high risk (35%) of vertical
      transmission of CMV infection by placenta. In group II with relative less risk of
      the vertical transmission (20%) in latent reactivated CMV infection in blood
      cells, especially, lymphocytes, the structural changes such apoptosis and
      necrosis were found. The data obtained suggest the presence of significant
      premorbid background with subclinical course of CMV infection and structural
      damages of blood cells in newborns.

PMID- 17525508
TI  - [Morphometric characteristic of the subepithelial connective tissue of the rabbit
      gingiva under the experimental gingivitis on the background of
      hypercholesterinemia].
AB  - The morphologic substrate of the gingival mucosa membrane during the increase of
      the proatherogenic lipids concentration and the damage the gingiva under the
      influence of the atherogenic diet was studied in experiment. By the planimetric
      method the middle indices of the number of capillaries, arterioles and venules
      and as well the quantities of immunocompetent cells (macrophages and lymphocytes)
      in the gingival subepithelial connective tissue were defined. The experiments
      were carried out on rabbits (race "Shinshila"). Animals were on atherogenic
      ration (cholesterol 0,3 g/kg with vegetables). The experimental gingivitis was
      modeled by ligation of a silk ligature around the dental neck of the tree
      superior basal teeth after peeling the gingiva. It was established that under the
      gingivitis developing against the background of hypercholesterinemia in the
      subepithelial layer of the gingival mucosa the degree of the vascularisation
      distinctly diminished, owing to the decrease the number of arteriols and partly
      capillaries and transformation their walls--the thin-walled capillaries with
      obliterated, deformated lumen appeared. Endotheliocites with changed structure,
      ordinary pycnosis of nuclei which creates the necessary prereqvisites for the
      disturbance of trophicity and progression of the inflammatory process.

PMID- 17525509
TI  - [Changes of concentration of renin-angiotensin system components during vibration
      and their correction in experiment].
AB  - The aim of the research was investigation of the state of rennin-angiotensin
      system during the vibration in rats. 40 (180-200gr) pubertal male rats were
      studied. One hour vibro seance was conducted every day during two months. The 60
      animals were divided into 3 groups (20 rats in each group); the third was control
      group. On 20th , 40th and 60th days of the experiment the decapitation of the
      animals was done under general narcosis. the Concentrations of rennin,
      angiotensin II and angiotensin converted ensyme in the blood plasma was
      determined using the method of radio immunoassay, The significant changes in
      concentrations of rennin-angiotensin system components have been manifested. The
      research showed the destruction in regulation of rennin-angiotensin system. It is
      concluded, that the vibration provokes the destruction of reciprocal feed-back of
      rennin-angiotensin system in the rats.

PMID- 17525510
TI  - [Experimental investigation of general toxiology of antioxidant eyedrops
      davicol].
AB  - Authors examined the toxicity of antioxidant eye drops--davikoli. Antioxidants
      play important role in protecting the body from the formation of very dangerous
      substances referred to as free radicals. On the basis of honey an eye drops with
      high antioxidant activity--davicoli has been developed. The ocular effects of eye
      drops have been measured in a placebo-controlled double-blind study in 44 mice,
      44 rats, 40 sea pigs and 20 chinchilla rabbits. Preclinical study revealed that
      eye drops davikoli are safe and non-toxic. During the investigation anti
      inflammation features of eye drops davicoli was discovered.

PMID- 17525511
TI  - Production of effervescent tablets Mucomali from polysaccharides of Malva
      Silvestris L.
AB  - The aim of the article was the estimation of efficiency of a method of production
      of effervescent tablets Mucomali from polysaccharides of Malva Silvestris L sum.
      The 5% polyethylene glycol solution of polyvinylpyrrolidone was used as
      connective agent. Experimentally was ascertained good solubility of effervescent
      tablets (Mucomali), produced from polysaccharide of Malva Silvestris L sum. The
      pressing power 110 mpa was found optimal for getting effervescent tablets of
      Mucomali.

PMID- 17525512
TI  - Particle-mediated gene delivery and human skin: ultrastructural observations on
      stratum corneum barrier structures.
AB  - The particle-mediated delivery systems are becoming a clinically relevant tool in
      dermatology and immunology. We investigated the qualitative ultrastructural
      morphology of skin following pressure-driven delivery of gold particles to ex
      vivo human breast skin, at different pressures ranging from 350 to 1,000 psi.
      Pressures of 800 and 1,000 psi appear to be more effective, as indicated by
      distribution of particles in the viable epidermis and dermis. Particle
      bombardment of the skin with gold beads caused microwounds that spanned the
      stratum corneum (SC). The SC lipids did not reseal these wounds in the SC after
      24 h in organ culture. The implications of particle-mediated delivery to
      permeability barrier functions of the SC are discussed.

PMID- 17525513
TI  - [A case of thrombophlebitis in superior mesenteric vein due to appendicitis].

PMID- 17525514
TI  - [Future direction of nanomedicine in gastrointestinal cancer].
AB  - Cancer is one of the leading causes of death in human, and among various cancers,
      gastrointestinal cancers occupy more than 55%. Gastric cancer is the first
      leading cause of cancer-related mortality in the world and the number of pancreas
      and colon cancers are increasing remarkably during last two decades which will
      continue to increase in the future. Even though the clinical importance of
      gastrointestinal cancers is very high and endless efforts has been made to
      develop novel diagnostic and therapeutic methods to improve the patient's quality
      of life and survival, the realistic advance in the actual survival benefit of the
      cancer patients are still strongly required. Nanotechnology has the power to
      radically change the way of cancer diagnosis and treatment. Currently, there is a
      lot of researches on novel nanodevices capable of detecting cancer at its
      earliest stage, pinpointing its location within the body, and delivering
      anticancer drugs specifically to the malignant cells. Nanoscale devices can
      readily interact with biomolecules both on the cell surface and within the cell.
      In addition, nanoscale devices are already proven that they can deliver
      therapeutic agents to target cells even within specific organelles. Major areas
      in which nanomedicine is being developed in cancer include early detection and
      proteomics, imaging diagnostics and multifunctional therapeutics. Because
      nanotechnology would provide a technical power and tool that enable new
      diagnostics, therapeutics, and preventives to keep pace with today's explosion in
      knowledge in the future, it would be very useful to know the perspectives in the
      direction of nanotechnology as a major clinician responsible for the patients
      with gastrointestinal malignancies.

PMID- 17525515
TI  - [Development of micro/nano devices for cancer diagnosis].
AB  - In order to rapidly detect and analyze the presence of a target ligand of
      interests in environmental or industrial fluids as well as biological samples,
      numerous test systems have been designed and developed, which have been based on
      the combination of a test reagent and absorbing paper or membrane. The main
      limitations of these conventional devices are the difficulty of quantitative or
      semi-quantitative detection and poor detection limit (around nanogram/ml range
      detection capability). In this paper, new approaches and research trends which
      use nano/MEMS (micro electro mechanical systems) technology is introduced, which
      has a concept of fast, precise, and massive diagnosis and analysis of target
      molecules using very small amount of samples.

PMID- 17525516
TI  - [Optical nano-imaging for the diagnosis of gastrointestinal cancers].
AB  - Development of in vivo animal imaging instrumentations and methods contributes to
      the early diagnosis of cancer. Of variable imaging modalities, in vivo optical
      imaging such as bioluminescence and fluorescence is one of the best methods to
      measure molecular change of cancer cells. High sensitivity and relatively low
      cost of optical method gives benefits to apply for translational research in the
      field of cancer. Nano-probes to label and detect early cancer cells have been
      developed by nano-chemists and molecular imaging researchers. Quantum dots made
      from fluorescent semi-conductors show good advantages in term of imaging probes;
      high quantum yields, large molar extinction coefficients, size-dependent tunable
      emission and high photostability. To detect a gastrointestinal (GI) cancer, newly
      developed endoscopes have been used. Among them, near infrared fluorescence
      endoscope and confocal endomicroscope are good candidates for clinical
      application. In animal studies, successful results to detect cancer in
      gastrointestinal tract have been obtained. Prospect of nanoparticles as optical
      imaging moiety is promising to detect GI cancers if their toxicity is minimized.
      Future fluorescence confocal endoscope with safe cancer targeting nanoparticles
      will be useful for the detection and treatment of GI cancers.

PMID- 17525517
TI  - [Drug-eluting stent in gastrointestinal disease].
AB  - Gastrointestinal (GI) cancers cause obstruction of the GI tract including biliary
      tree. In advanced GI cancer, endoscopic stent insertion is the treatment of
      choice. However, the current stent allows only mechanical palliation of
      obstructed GI tract and has no anti-tumor effect. The primary role of a drug
      eluting stent (DES) in gastrointestinal malignancy is that it decreases the tumor
      re-growth and sustains the stent patency. This might not be as impressive as the
      effect of a vascular DES which decreases the incidence of restenosis and thus
      increases the survival rate of the patient. However, in terms of improving the
      quality of life of the patient, maintaining the stent patency is one of the most
      important task of GI doctors. With an advanced technology in stent production,
      Korea would be able to play an active role in the field of DES especially with
      more advanced anti-tumor effect. Moreover, advances in this type of drug delivery
      system will enable the development of local treatment of GI malignancy using
      endoscopy.

PMID- 17525518
TI  - [Delivery of photosensitizers for photodynamic therapy].
AB  - Photodynamic therapy (PDT) has been used to treat several types of cancer, and
      comprises intravascular administration of photosensitizer, uptake by cancer
      cells, and followed by irradiation of light of appropriate wavelength. Although
      PDT takes advantage of relative retention of photosensitizer by cancer cells,
      effective delivery of photosensitizing drugs is of great concern. Several
      delivery strategies have been employed in PDT. Photosensitizers can be delivered
      either by passive carriers such as liposomes, micelles, and polymeric particles,
      or by active targeting using cancer cell-directed ligands or antibodies. Although
      well-studied colloidal carriers effectively deliver photosensitizer to tumor
      cells, they are taken up by mononuclear phagocytic system. Delivery system using
      polymers is an attractive alternative to colloidal carriers, in which hydrophobic
      drugs are chemically or physically loaded to polymers. Though there are several
      steps to be solved, targeted delivery system utilizing receptors or antigens
      abundantly expressed on cancer cell theoretically provides a great deal of
      advantages over passive system. Selective uptake of photosensitizers by cancer
      cells may greatly enhance therapeutic efficacy as well as minimizing adverse
      effects resulting from accumulation in normal tissue. This review discusses
      various strategies for photosensitizer delivery that have been investigated to
      date.

PMID- 17525519
TI  - [pH-sensitive polymeric micelles for the effective delivery of anti-cancer drug].
AB  - Polymeric micelles from pH-sensitive block copolymers have been designed for
      targeting tumor acidity or endosomal pH in tumor cells. The micelles are core
      shell types formed by self-organization of the blocks in an aqueous medium or
      under specific experimental conditions. They possess a segment that has physical
      or chemical properties responding to small changes in environmental pH. The
      segment induces to the fast release kinetics from the micelles at tumor sites by
      particle shrunk/disruption. Furthermore, it can alter the biodistribution of the
      micelles and the interactions with tissues and cells by utilizing small pH
      changes. Such properties lead to overcome the problems associated with free chemo
      agents, such as nonspecific toxicity, lack of tumor selectivity, and the
      development of multidrug resistance in various tumor cells. Therefore, the
      micelles have been considered as promising anti-cancer drug carriers. This review
      summarizes the recent progress in pH-sensitive micelles for tumor chemotherapy,
      particularly for those responding to tumor pH and endosomal/lysosomal pH for the
      treatment of multidrug resistance (MDR).

PMID- 17525520
TI  - [Long-term results of endoscopic histoacryl (N-butyl-2-cyanoacrylate) injection
      for treatment of gastric varices--a 10-year experience].
AB  - BACKGROUND/AIMS: Gastric variceal bleeding is an infrequent but serious
      complication of portal hypertension. Endoscopic injection of Histoacryl (N-butyl
      2-cyanoacrylate) has been approved as an effective treatment for gastric variceal
      bleeding. The aim of this study was to evaluate the long-term efficacy and safety
      of the endoscopic injection of Histoacryl for the treatment of gastric varices.
      METHODS: Between January 1994 and January 2005, eighty-five patients with gastric
      varices received endoscopic injections of Histoacryl. Among these 85 patients, 65
      received the procedure within 1 week after gastric variceal bleeding, and 13
      received as a prophylactic procedure. According to the Sarin classification, 32
      patients were GOV1 and 53 were GOV2. Most of the varices were large (F2 or F3, 75
      patients). The average volume of Histoacryl per each session was 1.43 ml. Among
      85 patients, 72 patients were followed-up and the median duration was 24.5
      months. RESULTS: The rate of initial hemostasis was 98.6% and recurrent bleeding
      occurred in 29.2% (21 of 72). When rebleeding occurred, 76.2% was within 1 year
      after the initial injection. Treatment failure-related mortality rate was 1.4% (1
      of 85). Twenty-seven patients died, mostly due to hepatocelluar carcinoma or
      liver failure. Two patients experienced pulmonary embolism and one experienced
      splenic infarction. They recovered without specific treatment. Rebleeding rate
      had a tendency to increase in patients with hepatocelluar carcinoma (p=0.051) and
      GOV2 (p=0.061). CONCLUSIONS: Histoacryl injection therapy is a effective
      treatment method for gastric varices with high initial hemostasis rate and low
      major complications.

PMID- 17525521
TI  - [A case of ulcerative colitis relapsed by influenza vaccination].
AB  - Although a large number of studies have reported the causes of the exacerbation
      of ulcerative colitis (UC), the effect of influenza vaccination on the relapse of
      UC has not been reported. We experienced a case of prompt exacerbation of
      quiescent UC due to influenza vaccination. A 39-year-old woman was diagnosed as
      UC 4-years ago and was well controlled with oral mesalazine. She experienced
      abdominal pain and frequent bowel movements with hematochezia 3 days after the
      vaccination. On admission, laboratory findings showed elevated erythrocyte
      sedimentation rate and C-reactive protein. Sigmoidoscopy showed marked edematous
      mucosa on rectum and sigmoid colon with fine ulceration and spontaneous bleeding.
      She recovered from the exacerbation of UC after steroid treatment. Vaccination
      should be administered to the patients with inflammatory bowel disease with the
      caution of its possible side effects.

PMID- 17525522
TI  - [A case of photodynamic therapy for early esophageal cancer recurred after
      esophagectomy].
AB  - Photodynamic therapy is a promising modality for the palliation of advanced upper
      gastrointestinal cancer and for the eradication of early neoplastic and pre
      neoplastic lesions. It is based on the combination of a photosensitizer that is
      selectively localized in the target tissue and illumination of the lesion with
      visible light, resulting in photodamage and subsequent cell death. For early
      esophageal cancer, esophagectomy has been a standard modality of curative intent.
      However, accumulated data supports the possibility of PDT replacing surgery as a
      curative modality. We experienced a case of early esophageal cancer that recurred
      after esophagectomy. The patient was successfully treated with photodynamic
      therapy using porfimer sodium as a photosensitizer.

PMID- 17525523
TI  - [A case of successful endoscopic injection sclerotherapy with N-butyl-2
      cyanoacrylate for ruptured duodenal varices].
AB  - Duodenal varix is a rare cause of hemorrhage in patients with portal
      hypertension, however their rupture is serious and often life threatening.
      Treatments for duodenal variceal bleeding include endoscopic procedures, surgery,
      or interventional radiologic procedures. We report a case of duodenal varices
      rupture in a 45-year-old man with alcoholic liver cirrhosis who presented with
      melena and dizziness. Emergent upper endoscopy revealed large nodular varices
      with a ruptured erosion on the top in the distal second portion of duodenum. Two
      consecutive injections with 1.0 mL of n-butyl-2-cyanoacrylate (Histoacryl; Braun
      Melsungen, Germany) mixed with 1.0 mL of lipiodol (Laboratoire-Guerbet, France)
      were performed intravariceally and achieved successful hemostasis. This suggests
      that endoscopic injection sclerotherapy with histoacryl may be an effective
      therapeutic option for the control of ruptured duodenal variceal bleeding.

PMID- 17525525
TI  - Contribution of Atg1-dependent autophagy to TOR-mediated cell growth and
      survival.
AB  - The Ser/Thr kinase Atg1 (Ulk1/Unc51) appears to act as a convergence point for
      multiple signals that regulate autophagy, and in turn interacts with a large
      number of autophagy-related (Atg) proteins. Working in the Drosophila system, we
      recently found that overexpression of Atg1 is sufficient to induce autophagy,
      independent of upstream nutrient signals. We exploited this finding to examine
      the roles of autophagy in cell growth and death, and to test the interaction of
      Atg1 with the TOR signaling pathway. These studies provided genetic evidence that
      autophagy is a potent inhibitor of cell growth, and that high levels of autophagy
      lead to caspase-dependent apoptotic cell death in vivo. Atg1 also has an
      inhibitory effect on TOR signaling, indicating the existence of a positive
      feedback mechanism that may amplify the nutrient-dependent signals that control
      autophagy.

PMID- 17525526
TI  - Research by retrieving experiments.
AB  - Newton did not discover that apples fall: the information was available prior to
      his gravitational hypothesis. Hypotheses can be tested not only by performing
      experiments but also by retrieving experiments from the literature (via PubMed,
      for example). Here I show how disconnected facts from known data, if properly
      connected, can generate novel predictions testable in turn by other published
      data. With examples from cell cycle, aging, cancer and other fields of biology
      and medicine, I discuss how new knowledge was and will be derived from old
      information. Millions of experiments have been already performed to test
      unrelated hypotheses and the results of those experiments are available to 'test'
      your hypotheses too. But most data (99% by some estimates) remain unpublished,
      because they were negative, seemed of low priority, or did not fit the story. Yet
      for other investigators those data may be valuable. The well-known story of
      Franklin and Watson is a case in point. By making preliminary data widely
      available, 'data-owners' will benefit most, receiving the credit for otherwise
      unused results. If posted (pre-published) on searchable databases, these data may
      fuel thousands of projects without the need for repetitive experiments. Enormous
      'pre-published' databases coupled with Google-like search engines can change the
      structure of scientific research, and shrinking funding will make this
      inevitable.

PMID- 17525527
TI  - Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated
      invasion of cancer cells.
AB  - Hepatocyte growth factor (HGF) receptor Met and hypoxia-inducible factor-1 (HIF
      1) signaling pathways are commonly activated in aggressive tumors and promote
      progression. Since both Met and HIF-1alpha proteins are heat shock protein (Hsp)
      90 clients, Hsp90 inhibitors might be expected to positively impact tumor
      progression. Here, we systematically evaluated the inhibitory effects of the
      prototypical Hsp90 inhibitor geldanamycin (GA) on cellular processes involved in
      invasion and angiogenesis in T24 bladder cancer cells stimulated with HGF and
      chemical hypoxia. First, we demonstrated the positive feedback loop between Met
      and HIF-1 pathways, which serves to sustain and amplifies their signaling in T24
      cells. GA downregulated Met by inhibiting new protein maturation, thereby
      dampening HGF signaling. HGF and chemical hypoxia with CoCl2 cooperatively
      promoted in vitro invasion and vascular endothelial growth factor (VEGF)
      secretion, while CoCl2 but not HGF activated urokinase-type plasminogen activator
      and matrix metalloproteinase 2, both of which promote invasion and angiogenesis.
      Low dose GA (100 nmol/L) inhibited these processes by suppressing both HGF and
      HIF-1 pathways. Notably, brief GA pretreatment inhibited in vitro invasion and
      VEGF secretion induced by HGF as effectively as did continuous treatment.
      Moreover, we found that GA inhibited activation of focal adhesion kinase, focal
      adhesion assembly, and actin reorganization induced by HGF and integrin
      engagement by extracellular matrix. Thus, GA widely suppresses extrinsic stimuli
      induced signaling that contribute to tumor invasion and angiogenesis in this
      bladder carcinoma model, suggesting the utility of Hsp90 inhibitors in preventing
      tumor progression and metastasis.

PMID- 17525528
TI  - BubR1 and CENP-E have antagonistic effects upon the stability of microtubule
      kinetochore attachments in Drosophila S2 cell mitosis.
AB  - The spindle assembly checkpoint ensures the fidelity of chromosome segregation at
      each cell division cycle. Previous reports have indicated that in higher
      eukaryotes checkpoint proteins, such as BubR1, are also implicated in chromosome
      congression, more specifically that BubR1 regulates chromosome-spindle
      attachments. Also, several studies have shown that BubR1 interacts with the
      microtubule motor protein CENP-E. Whether this association contributes to the
      regulation of chromosome-spindle attachments is not yet known. Accordingly, we
      performed a detailed analysis of microtubule-kinetochore interactions after
      depletion of BubR1 and the Drosophila CENP-E homolog, CENP-meta by RNAi. We find
      that depletion of BubR1 affects mitosis very differently from depletion of CENP
      meta. While BubR1-depleted cells exit mitosis prematurely due to loss of SAC
      activity, CENP-meta-depleted cells accumulate in prometaphase and do not exit
      mitosis after spindle damage. Also, in contrast to cells depleted for CENP-meta,
      cells depleted for BubR1 very rarely reach full metaphase alignment even if
      arrested in mitosis with the proteasome inhibitor MG132. More importantly, we
      show for the first time that BubR1-depleted cells contain a high frequency of
      either monoriented or fully unattached chromosomes while most CENP-meta dsRNAi
      treated cells have chromosomes attached to spindle microtubules. Moreover,
      simultaneous depletion of both proteins reveals that absence of CENP-meta is able
      to partially rescue the unattached chromosome phenotype observed after BubR1
      depletion. These results strongly suggest that while BubR1 is required to promote
      stable microtubule kinetochore attachment, CENP-E appears to be required to
      destabilize kinetochore attachment. Overall our results suggest that activation
      of the mechanism that corrects inappropriate kinetochore attachment requires the
      antagonistic effects of BubR1 and CENP-E.

PMID- 17525529
TI  - CDK4 inhibitors and apoptosis: a novel mechanism requiring nucleolar targeting of
      RelA.
AB  - Components of the cyclin D-CDK4/6-INK4-Rb pathway are key regulators of the cell
      cycle and are frequently disrupted in cancer. Defects in this pathway usually
      manifest as an increase in CDK4 activity, leading to unrestricted proliferation
      of tumour cells. CDK4 inhibitors have been shown to possess anti-tumour activity
      in vitro and agents that target the cyclin D1/CDK4 complex are currently the
      focus of intense scrutiny for clinical application as cancer therapeutics.
      However, the mechanisms by which these agents mediate their effects remains to be
      fully elucidated. We recently described a novel mechanism by which a CDK4
      inhibitor induces apoptosis in colon cancer cells through activation of the NFkB
      signaling pathway. Specific inhibition of CDK4 activity induced translocation of
      RelA, the principal component of NFkappaB, from the cytoplasm to the nucleoplasm
      and then to the nucleolus. This was accompanied by a repression of NFkappaB
      driven transcription and apoptosis of the cancer cells. To determine the role of
      RelA in apoptosis, we utilised a mutant form of the protein, where the critical
      domain required for nucleolar targeting had been deleted. When cells expressing
      this mutant protein were treated with the CDK4 inhibitor, RelA translocated from
      the cytoplasm to the nucleoplasm, but was excluded from the nucleolus.
      Furthermore, apoptosis induced by CDK4 inhibition was also abrogated in cells
      expressing mutant RelA protein. Here, we discuss the molecular mechanisms that
      regulate programmed cell death induced by disruption of the cyclin D1/CDK4
      complex and consider the wider implications these findings have for the future
      development of novel chemotherapeutic agents.

PMID- 17525530
TI  - STAT3 and PKC differentially regulate telomerase activity during megakaryocytic
      differentiation of K562 cells.
AB  - Telomerase is active in immature somatic cells, but not in differentiated cells.
      However, the regulation during cell differentiation is not well understood. In
      this study, a human chronic myelogenous leukemia cell line (K562) was induced to
      differentiate into megakaryocytes by TPA, and erythroid by STI571. A human acute
      myeloblastic leukemia cell line (HL60) was also induced to differentiate into
      monocytes by TPA and VD3, and granulocyte by ATRA. TPA induced transient increase
      of telomerase activity (mainly nuclear fraction) during megakaryocytic
      differentiation, while the expression of hTERT decreased gradually throughout the
      same period. Pretreatment with PKC inhibitors inhibited the megakaryocytic
      differentiation, transient increase of telomerase activity, while recombinant PKC
      increased telomerase activity. ChIP assay resulted STAT3 and STAT5 dissociated
      from the hTERT promoter, indicating that STAT3 and STAT5 are one of the
      transcriptional regulators. These results suggest that telomerase activity is
      regulated by two mechanisms during megakaryocytic differentiation.

PMID- 17525531
TI  - Differential repression of c-myc and cdc2 gene expression by ERF and PE-1/METS.
AB  - The molecular mechanisms that control the proliferation and differentiation of
      specific cell types remain poorly understood. Positive ETS factors play important
      roles in mediating proliferative responses to Ras/MAPK signaling in many cell
      types following mitogenic stimulation. PE-1/METS, a member of the ETS-domain
      family transcription factors that functions as a transcriptional repressor, can
      block mitogenic responses mediated by positively acting Ets factors. The anti
      proliferative functions of PE-1/METS require its interaction with DP103, a
      multifunctional DEAD-box protein that mediates interactions with corepressor
      proteins and acts in a cooperative manner with Rb family members and to repress
      cell cycle control genes. ETS-2 repressor factor (ERF) is structurally related to
      and also functions as a transcriptional repressor, but endogenous target genes
      and mechanisms of repression remain unknown. Here, we demonstrate that like PE
      1/METS, ERF-mediated repression also requires DP103, and that ERF negatively
      regulates the c-myc and cdc2 genes. In contrast to PE-1/METS, however, ERF
      mediated repression of these genes is inactivated by MAPK signaling through
      phosphorylation sites that are ERF-specific. Furthermore, constitutive activation
      of the Ras/MAPK pathway in RAW 264.7 cells transformed by the v-Abelson leukemia
      virus is associated with constitutive inactivation of ERF in this cell type. We
      propose that ERF and PE-1/METS function to impose 'repression checkpoints' on a
      subset of cell cycle control genes that are differentially regulated by growth
      factor signaling pathways that control proliferation and differentiation and that
      ERF is targeted for inactivation by transforming oncogenes such as vAbl.

PMID- 17525532
TI  - Redirecting the assessment of clinical competence.

PMID- 17525533
TI  - A performance-based conception of competence is changing the regulation of
      physicians' professional behavior.
AB  - It is the obligation of a profession to articulate the special meaning of
      competence in its field and to foster the good performance of its practitioners
      through education and discipline. External societal demands for increased
      accountability, and internal pressures for greater use of measurements of the
      processes and outcomes of clinical performance, are forcing the medical
      profession to reevaluate its view of competence and to change the way the
      profession "manages" the competence of its members. Traditionally, and predicated
      on the notion of "once in, good for life," medical education has focused on
      assuring the competence of trainees as they first enter independent professional
      life. In parallel, professional regulatory authorities have concentrated on
      apprehending the "false-positives" of the educational system. But viewed from a
      performance orientation, competence reflects situational relationships among
      doctors, their patients, and the systems in which they perform and, thus, is only
      partly dependent on the attributes of individual actors. This shift in thinking
      has major implications for the practice of medicine, particularly for the process
      of maintaining and improving performance. In jurisdictions throughout the world,
      recognition of the need for systematic and accountable ongoing education for
      practicing doctors is growing. This educational need should not be seen as a mark
      of weakness or failure but, rather, as the natural consequence of engagement in
      challenging practice. "Ars longa, vita breva." The profession must address the
      complex issues of education-in-practice with the same determination and
      creativity that it previously applied to education at entry to practice.

PMID- 17525534
TI  - No time for kids!

PMID- 17525535
TI  - Taking apart the art: the risk of anatomizing clinical competence.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) is encouraging
      medical residency programs to objectively assess their trainees for possession of
      six general clinical competencies by the completion of residency training. This
      is the thrust of the ACGME Outcome Project, now in its seventh year. As residency
      programs seek to integrate the general competencies into clinical training,
      educators have begun to suggest that objective assessment of clinical competence
      may be able to guide decisions about length of training and timing of
      subspecialization. The authors contend that higher-level competence is not
      amenable to assessment by the objective comparison of resident performance with
      learning objectives, even if such objectives are derived from general
      competencies. Present-day attempts at such assessment echo the uses to which
      medical schools hoped to put curricular learning objectives in the 1970s.
      Objective assessment may capture knowledge and skills that amount to the
      "building blocks" of competence, but it cannot elucidate or scrutinize higher
      level clinical competence. Higher-level competence involves sensitivity to
      clinical context and can be validly appraised only in such a context by fully
      competent clinical appraisers. Such assessment is necessarily subjective, but it
      need not be unreproducible if raters are trained and if sampling of trainee
      performance is sufficiently extensive. If the ACGME approach to clinical
      competency is indeed brought to bear on decisions about training length and
      subspecialization timing, the present apprenticeship model for clinical training
      in the United States, a model both remarkably successful and directly descendant
      from Osler's innovations, will be under threat.

PMID- 17525536
TI  - Competency-based postgraduate training: can we bridge the gap between theory and
      clinical practice?
AB  - The introduction of competency-based postgraduate medical training, as recently
      stimulated by national governing bodies in Canada, the United States, the United
      Kingdom, The Netherlands, and other countries, is a major advancement, but at the
      same time it evokes critical issues of curricular implementation. A source of
      concern is the translation of general competencies into the practice of clinical
      teaching. The authors observe confusion around the term competency, which may
      have adverse effects when a teaching and assessment program is to be designed.
      This article aims to clarify the competency terminology. To connect the ideas
      behind a competency framework with the work environment of patient care, the
      authors propose to analyze the critical activities of professional practice and
      relate these to predetermined competencies. The use of entrustable professional
      activities (EPAs) and statements of awarded responsibility (STARs) may bridge a
      potential gap between the theory of competency-based education and clinical
      practice. EPAs reflect those activities that together constitute the profession.
      Carrying out most of these EPAs requires the possession of several competencies.
      The authors propose not to go to great lengths to assess competencies as such, in
      the way they are abstractly defined in competency frameworks but, instead, to
      focus on the observation of concrete critical clinical activities and to infer
      the presence of multiple competencies from several observed activities. Residents
      may then be awarded responsibility for EPAs. This can serve to move toward
      competency-based training, in which a flexible length of training is possible and
      the outcome of training becomes more important than its length.

PMID- 17525538
TI  - Measures of cultural competence: examining hidden assumptions.
AB  - PURPOSE: The authors critically examined the quantitative measures of cultural
      competence most commonly used in medicine and in the health professions, to
      identify underlying assumptions about what constitutes competent practice across
      social and cultural diversity. METHOD: A systematic review of approximately 20
      years of literature listed in PubMed, the Cumulative Index of Nursing and Allied
      Health Literature, Social Services Abstracts, and the Educational Resources
      Information Center identified the most frequently used cultural competence
      measures, which were then thematically analyzed following a structured analytic
      guide. RESULTS: Fifty-four instruments were identified; the 10 most widely used
      were analyzed closely, identifying six prominent assumptions embedded in the
      measures. In general, these instruments equate culture with ethnicity and race
      and conceptualize culture as an attribute possessed by the ethnic or racialized
      Other. Cultural incompetence is presumed to arise from a lack of exposure to and
      knowledge of the Other, and also from individual biases, prejudices, and acts of
      discrimination. Many instruments assume that practitioners are white and Western
      and that greater confidence and comfort among practitioners signify increased
      cultural competence. CONCLUSIONS: Existing measures embed highly problematic
      assumptions about what constitutes cultural competence. They ignore the power
      relations of social inequality and assume that individual knowledge and self
      confidence are sufficient for change. Developing measures that assess cultural
      humility and/or assess actual practice are needed if educators in the health
      professions and health professionals are to move forward in efforts to
      understand, teach, practice, and evaluate cultural competence.

PMID- 17525539
TI  - Cultural competence teaching in U.S. pediatric clerkships in 2006.
AB  - PURPOSE: Cultural sensitivity may be especially important in the care of
      children, and national pediatric associations have issued policy statements
      promoting cultural competence in medical education. The authors conducted a
      national survey to investigate the current state of cultural competence teaching
      and learning within U.S. pediatric clerkships. METHOD: The authors surveyed 125
      U.S. pediatric clerkship directors concerning the presence or absence of cultural
      curricula, content, teaching methods, and evaluation. Question types were
      multiple-choice single/best answer, checklists, five-point Likert-type scales,
      and free-text responses. RESULTS: Of 100 respondents (80% response rate), most
      agreed or strongly agreed that teaching culturally competent care is important
      (91%), enhances the physician/patient/family relationship (99%), and improves
      patient outcomes (90%). Twenty four of 98 respondents (25%) reported cultural
      competence teaching. The most common teaching methods were lectures (63%),
      experiential learning through community activities (58%), and small-group
      discussions (54%). Only 14 respondents reported any curricular evaluation, the
      commonest methods being student surveys, clinical case presentations, and
      standardized patient experiences. Top factors facilitating curriculum development
      were culturally diverse populations of patients, students, faculty, and hospital
      staff, and faculty interest and expertise. Top challenges included lack of
      protected time for program development, funding, and faculty expertise.
      CONCLUSIONS: Few U.S. pediatric clerkships currently provide cultural competence
      curricula. The authors' suggestions to promote cultural competence teaching
      include providing faculty development opportunities and developing and
      disseminating teaching materials and evaluation tools. Such dissemination is
      important to graduate physicians, who can provide culturally sensitive pediatric
      care to the changing U.S. population.

PMID- 17525540
TI  - Introduction to core competencies in residency: a description of an intensive,
      integrated, multispecialty teaching program.
AB  - Postgraduate residency programs must ensure that residents are properly trained
      in all core competencies. The CanMEDS framework of the Royal College of
      Physicians and Surgeons of Canada has established seven such competencies:
      medical expert, communicator, collaborator, manager, health advocate, scholar,
      and professional. The authors describe an integrated, one-month multispecialty
      rotation for first-year residents, Introduction to CanMEDS Core Competencies, at
      Laval University, Quebec, Canada. The goal of the rotation was to offer an in
      depth and simultaneous training in each of the seven competencies. A pilot
      rotation was offered from February 9 to March 7, 2004 and involved 42 residents
      from seven programs and 30 faculty. It addressed 12 content areas related to the
      core competencies, through teaching formats promoting experiential and reflective
      learning. It involved three significant innovations: an intensive month-long
      format, during which residents were freed from most clinical duties; a
      multispecialty teaching and socialization strategy between peers and with
      faculty; and an integrated reflective approach, to ensure residents'
      understanding of the relevance and application of the core competencies in their
      own specialty. Although demanding to organize, the pilot rotation was well
      received. Residents were rapidly introduced to all competencies, and they
      developed an integrated perspective of them. An evaluation of impact is underway.

PMID- 17525542
TI  - Competency in surgical residency training: defining and raising the bar.
AB  - Competency-based surgical residency training is rapidly becoming the norm across
      surgical specialties. Ensuring that graduating surgeons are competent to deliver
      the necessary services and skills to their patients remains a seminal objective
      of training programs. Defining surgical competence, the measures used to assess
      and quantify that competence, and the criteria used to judge whether it has been
      achieved are critical issues. The bar that surgical residency programs have
      established is, and must continue to be, set very high. Definitions of competency
      differ across disciplines. In education, two approaches are recognized. According
      to the behaviorist approach, competence is assessed by precise measures of
      performance, generally documented by checklists. The integrated (holistic)
      approach defines competence as a complex combination of personal attributes.
      Assessments of competence also fall under two categories: the traditional
      scientific paradigm, emphasizing objectivity and reproducibility, and the
      judgment paradigm, reflecting the need to assess clinical competence in the final
      stages of medical training. In surgery, competence is the ability to successfully
      apply professional knowledge, skills, and attitudes to new situations as well as
      to familiar tasks. A critical step in assessing surgical competency is developing
      methodology for competency evaluation and certification. Matching different
      aspects of surgical competency with the appropriate assessment instruments is the
      theme of the contemporary evaluation process, with emphasis on a whole-task
      approach and the assessment of professional judgment. An effective assessment
      program will incorporate several competency elements, using multiple sources of
      information to assess competencies on multiple occasions, at various levels, and
      in different settings.

PMID- 17525543
TI  - Are we serious about teaching professionalism in medicine?
AB  - Medical professionalism is an increasingly common topic of discussion in the
      medical education literature. Much of the recent literature on this subject
      addresses areas of weakness in the educational curricula of medical schools and
      residency programs. But students are living a world in which professional
      behavior is being redefined, often in ways that run contrary to the medical
      education curriculum. This article outlines three fundamental challenges that
      powerfully affect the ability to promote professionalism in students and young
      physicians. To overcome these challenges, the author suggests four steps that can
      be taken in the medical education community. First, medical schools should
      address cost and access to care as first-order intellectual problems and should
      encourage research programs in these areas. Second, schools should develop
      programs to humanize science and restore scientific integrity beyond the
      requirements of compliance programs. Next, medical school leaders should
      celebrate those who best embody moral leadership in the profession. Finally, the
      medical education community should acknowledge that the availability of
      affordable health care to the public depends on the practice choices of medical
      school graduates and should accept greater responsibility for this outcome.

PMID- 17525545
TI  - Can there be a single system for peer assessment of professionalism among medical
      students? A multi-institutional study.
AB  - PURPOSE: Peer assessment is a valuable source of information about medical
      students' professionalism. How best to facilitate peer assessment of students'
      professional behavior remains to be answered, however. This report extends
      previous research through a multi-institutional study of students' perspectives
      about system characteristics for peer assessment of professionalism. It examines
      whether students from different schools and year levels prefer different
      characteristics of peer assessment to assess each other candidly, or whether a
      single system can be designed. It then identifies the characteristics of the
      resulting preferred system(s). METHOD: At the beginning of academic year 2004
      2005, students (1,661 of 2,115; 78%) in years one through four at four schools
      replied to a survey about which peer assessment characteristics - related to, for
      example, who receives the assessment, its anonymity, and timing - would prevent
      or encourage their participation. Multivariate analysis of variance was used to
      detect differences among institutions and students from each year level. RESULTS:
      Students across year levels and schools generally agreed about the
      characteristics of peer assessment. They prefer a system that is 100% anonymous,
      provides immediate feedback, focuses on both unprofessional and professional
      behaviors, and uses peer assessment formatively while rewarding exemplary
      behavior and addressing serious repetitive professional lapses. The system, they
      emphasize, must be embedded in a supportive environment. CONCLUSIONS: Students'
      agreement about peer-assessment characteristics suggests that one system can be
      created to meet the majority of students' preferences. Once implemented, the
      system should be monitored for student acceptability to maximize participation
      and to determine the formative and summative value of the process.

PMID- 17525546
TI  - A prospective study of the relationship between medical knowledge and
      professionalism among internal medicine residents.
AB  - PURPOSE: To explore residents' competency in medical knowledge and in empathy,
      one element of professionalism, and to evaluate the relationship between
      competencies in these domains. METHOD: In 2003-2004 and 2004-2005, first-year
      internal medicine residents at the Mayo Clinic College of Medicine in Rochester,
      Minnesota were invited to participate in a prospective, longitudinal study of
      resident competency. Participating residents completed the annual Internal
      Medicine In-Training Examination (ITE) each October and the Interpersonal
      Reactivity Index (IRI), a standardized tool to measure empathy administered at
      multiple time points during training. Changes in medical knowledge and empathy
      between the fall of postgraduate years one and two were evaluated, and
      associations between medical knowledge and empathy were explored. RESULTS:
      Residents' medical knowledge as measured by the ITE increased over the first year
      of training (mean increase 8.7 points, P < .0001), whereas empathy as measured by
      the empathic concern subscale of the IRI decreased over this same time period
      (mean decrease 1.6 points, P = .0003). No significant correlation was found
      between medical knowledge and empathy or between changes in these domains of
      competency over time. CONCLUSIONS: Resident competency in the domains of medical
      knowledge and empathy seems to be influenced by separate and independent aspects
      of training. Training environments may promote competency in one domain while
      simultaneously eroding competency in another. Residency programs should devise
      specific curricula to promote each domain of physician competency.

PMID- 17525548
TI  - Medicine and the arts. Rowing without Oars [excerpt] by Ulla-Carin Lindquist.
      Commentary.

PMID- 17525550
TI  - Burnout in residents of otolaryngology-head and neck surgery: a national inquiry
      into the health of residency training.
AB  - PURPOSE: To characterize resident burnout on a national scale with a large sample
      size and to identify associated modifiable factors to minimize burnout and
      improve the quality of residency education. METHOD: A survey was mailed to all
      1,364 U.S. residents of otolaryngology-head and neck surgery in September 2005.
      The main outcome measures were the Maslach Burnout Inventory-Human Services
      Study, demographic information, and potential burnout predictors, including
      stressors, satisfaction, self-efficacy, and support systems. RESULTS: The
      response rate was 50% (684/1,364). Current second-year through fifth-year
      residents were included for further analysis (514). Burnout was extremely common
      among otolaryngology residents. High burnout was seen in 10% of residents (51),
      moderate burnout in 76% (391), and low burnout in 14% (72). The strongest
      associated demographic factor was work hours (P < .001). Hours worked was
      predictive of emotional exhaustion, with exhaustion scores rising by 0.19 for
      each hour worked (P < .001). Furthermore, there was an 8% (41 resident) reported
      violation rate of the Accreditation Council for Graduate Medical Education
      (ACGME) 80-hour-workweek limitation. Satisfaction with the balance between
      personal and professional life, relationship stability, and satisfaction with
      career choice were negatively associated with burnout (all P < .001).
      CONCLUSIONS: Burnout is widely prevalent among U.S. otolaryngology residents and
      is present at greater levels than those seen in chairs or faculty of the same
      specialty. Work hours predict emotional exhaustion, and adherence to the ACGME 80
      hour workweek may help protect against burnout and its deleterious consequences
      in residents of all specialties.

PMID- 17525551
TI  - Obstetrician-gynecologists and primary care: training during obstetrics
      gynecology residency and current practice patterns.
AB  - PURPOSE: To assess obstetrician-gynecologists' perceptions of their residency
      training in primary care, document health issues assessed at annual visits, and
      identify practice patterns of both generalist and specialist obstetrician
      gynecologists. METHOD: Questionnaires were mailed to a random sample of 1,711
      American College of Obstetricians and Gynecologists Young Fellows in September
      2005. Information was gathered on perceptions about adequacy of residency
      training, how well training prepared obstetrician-gynecologists for current
      practice, and typical practice patterns for various medical diagnoses. Data were
      analyzed using univariate analysis of variance, t tests, and chi-square tests.
      RESULTS: Of 935 respondents (55% response rate), physicians estimated that 37% of
      private, nonpregnant patients rely on them for routine primary care.
      Approximately 22% report that they needed additional primary care training,
      specifically for metabolism/nutrition and dermatologic, cardiovascular, and
      psychosexual disorders. A wide range of topics, except for immunizations, were
      typically discussed at annual visits. Patients with pulmonary diseases, vascular
      diseases, and nongenital cancers were most often referred to specialists, whereas
      patients with urinary tract infections, sexually transmitted infections, or who
      are menopausal are most often managed totally. Self-identification as a
      generalist or specialist was associated with some practice patterns. Respondents
      were neutral about the role of primary care in obstetrics-gynecology residency
      training. CONCLUSIONS: For several primary care issues, obstetrician
      gynecologists assumed sole management for obstetric patients but deferred to a
      primary care physician for gynecological patients. There is a continuing need for
      primary care training in obstetrics-gynecology residency, although it is unclear
      whether current training is adequate to meet their needs.

PMID- 17525552
TI  - Program report cards: evaluation across multiple residency programs at one
      institution.
AB  - The designated institution official (DIO) is responsible for monitoring all
      residency programs within an institution. Although program-evaluation tools have
      been developed for residency program directors to use, there are currently no
      such published evaluation tools for DIOs. This manuscript describes the
      development and implementation of a standardized, dimensional program report card
      for the more than 60 residency and fellowship programs at our institution. This
      report card measures the theoretical construct of residency program performance
      and is divided into four sections: (1) quality of candidates recruited, (2) the
      resident educational program, (3) graduate success, and (4) overall house officer
      satisfaction. Each section is measured by objective and subjective metrics that
      allow the DIO to record programmatic strengths and weaknesses. These results are
      confidentially shared with the residency program director and encourage a
      partnership between the DIO and the program director. It is difficult to provide
      concrete construct validity with this instrument. The process used to develop the
      report card seems valid. The authors recognize that this report card is a
      surrogate for each program's RRC's perception of quality. In the future, the
      authors hope to work closely with the Accreditation Council for Graduate Medical
      Education and/or the group on resident affairs of the Association of American
      Medical Colleges to set national benchmark criteria for acceptable residency
      program performance for each medical discipline. They hope that DIOs and program
      directors will be able to compare residency programs objectively and identify
      areas for improvement at a local and national level.

PMID- 17525553
TI  - Introducing the concept of epistemological beliefs into medical education: the
      hot-air-balloon metaphor.
AB  - The authors draw attention to the need to introduce the concept of
      epistemological beliefs into medical education. Epistemological beliefs are the
      cognitions (i.e., understandings) individuals have on knowledge and knowing and
      determine how (new) knowledge is perceived and processed. Within educational
      psychology, three different frameworks have been used to study epistemological
      beliefs. The authors describe these three frameworks and discuss their
      applicability and their significance for phrasing and studying issues that
      intuitively seem essential to medical educators. The metaphor of a piloted hot
      air balloon illustrates the different factors contributing to medical expertise:
      the hot-air balloon's basket symbolizes the well-organized knowledge base, the
      envelope (i.e., air bag) stands for the skills repertoire of the pilot, and the
      burners represent motivation, intelligence, and other noncognitive factors. The
      pilot needs to achieve sophisticated levels of epistemological beliefs and
      metacognitive skills to be able to reach the upper levels of expertise with his
      well-equipped balloon. The metaphor emphasizes the dynamic disposition of
      expertise and offers a visual framework for designing curricula, assessment
      procedures, and educational research projects. Future research into medical
      students' epistemological beliefs should focus on outcome measures that are
      relevant within the medical education setting, and must take into account a
      number of pitfalls and difficulties inherent both in the concept of
      epistemological beliefs and in research in medical education.

PMID- 17525555
TI  - Autonomic dysreflexia and sudden death in people with traumatic spinal cord
      injury.
AB  - Autonomic dysreflexia (AD) is an uncommon but potentially life-threatening
      clinical syndrome consisting of acute episodes of excessive, uncontrolled
      sympathetic output that may occur in quadriplegics and in paraplegics whose
      spinal cord lesions are above the level of T6. These uncontrolled bouts of
      sympathetic output can cause transient and pronounced elevations of blood
      pressure that on occasion can lead to serious sequela such as the precipitation
      of a hypertensive intracerebral hemorrhage. The episodes of AD are often
      triggered by some type of noxious stimulus such as a distended urinary bladder or
      a fecal impaction. We present the case of a 62-year-old man with a history of
      quadriplegia resulting from a diving accident 40 years ago that was complicated
      clinically by episodes of autonomic dysreflexia. While hospitalized, he
      experienced an episode of autonomic dysreflexia with severe hypertension, which
      was soon followed by neurologic deterioration and death. Antemortem imaging
      revealed a large hypertensive-type intracerebral hemorrhage originating in his
      right caudate nucleus. Although his death at first appeared to be a natural death
      due to a spontaneous hypertensive-type intracerebral hemorrhage, his clinically
      documented autonomic dysreflexia convincingly linked the remote spinal cord
      injury and the fatal intracerebral hemorrhage, engendering an accidental manner
      of death.

PMID- 17525556
TI  - Shotgun wounds: a review of range and location as pertaining to manner of death.
AB  - Shotguns are used in a considerable number of homicides and suicides, and while
      gunshot wounds are extensively reported in the literature, there is a paucity of
      shotgun deaths. To specifically study deaths by shotguns, all deaths due to
      shotguns examined at the Bexar County Medical Examiner's Office between 1988 and
      2005 were reviewed. The cases were evaluated by age and sex of the victim, wound
      location, wound range, and manner of death. Three hundred eighty-seven cases were
      evaluated, composed of 343 males and 44 females, with 180 homicides, 203
      suicides, 3 accidents, and 1 undetermined manner of death. Contact wounds were
      the most common range in suicides and the head was the most common location. For
      homicides, the most common range of fire was distant, and the most prevalent
      distributions of wounds were head, chest, and multiple wound locations.
      Statistical analysis showed significant differences between homicide and suicide
      wound locations and ranges, and then odds ratios were generated. Knowledge of the
      statistical distribution of shotgun wounds in a large series with respect to
      range of fire and wound location may be of assistance to the medical examiner in
      evaluating the circumstances of an individual case to arrive at a manner-of-death
      opinion.

PMID- 17525557
TI  - The predictive value of history and scene investigation for toxicology results in
      a medical examiner population.
AB  - Medical examiner offices vary in the extent to which they pursue postmortem
      toxicology. Our office routinely tests decedents for ethanol and drugs of abuse,
      and we decided to evaluate the usefulness of our practice. We reviewed 1180
      medical examiner cases examined in 2002-2003. History and scene investigation
      indicated that alcohol or drugs of abuse were likely to be detected in 369 cases,
      yet toxicology testing revealed an intoxicating substance in 589 cases, a
      prevalence of 50%. Screening for toxicology testing based on investigative
      findings had a sensitivity of 0.47, a specificity of 0.84, and a positive
      predictive value of 0.74. Moreover, even in the 811 cases where initial
      investigation did not suggest substance abuse, toxicology testing revealed at
      least 1 substance that was pertinent to the subsequent investigation in one third
      of the cases (260), and the intoxicating substance was sufficiently important to
      merit inclusion as a cause of death or contributing factor in nearly half of
      those cases (113). We conclude that investigation alone is ineffective at
      predicting the presence of intoxicating substances within decedents.

PMID- 17525558
TI  - Rib fractures in infants due to cardiopulmonary resuscitation efforts.
AB  - Although it is widely known that adults may sustain fractures of the anterior
      and/or lateral aspects of the ribs due to cardiopulmonary resuscitation (CPR)
      efforts, relatively little is written about the generation of CPR-related rib
      fractures in the infant age range. In a series of 70 consecutive autopsies in
      infants ranging in age from 2 weeks to 8 months, with no history or indications
      of injury, the parietal pleura of the thoracic cage was stripped and the ribs
      carefully examined for fracture. Subtle fractures of the anterolateral aspects of
      the ribs were discovered in 8 (11%) of the 70 cases. In 7 of the 8 cases,
      multiple ribs were fractured (ranging up to 10 rib fractures), and in 5 of these
      cases, the rib fractures were bilateral. All of the rib fractures were subtle,
      had little if any associated blood extravasation, and would have been easily
      missed had the parietal pleura not been stripped. These anterolateral rib
      fractures in infants are the likely correlate of anterolateral rib fractures that
      are not uncommonly seen in the adult population, resulting from resuscitation
      efforts. The rib fractures are subtle and may not be identified unless the
      parietal pleura is stripped.

PMID- 17525559
TI  - The sensitivity and specificity of control surface injuries in aircraft accident
      fatalities.
AB  - Among the important determinations that aircraft crash investigators try to make
      is which occupant of an aircraft was attempting to control the aircraft at the
      time of the crash. The presence or absence of certain injuries of the extremities
      is used to help make this determination. These "control surface injuries"
      reportedly occur when crash forces are applied to a pilot's hands and feet
      through the aircraft's controls. We sought to clarify the significance of these
      injuries and the frequency with which their presence indicates that the decedent
      was the person that might have been trying to control the aircraft, questions
      that are frequently asked of the examining pathologist. We studied sequential
      fatalities of airplane and helicopter crashes in which autopsies were performed
      by the Office of the Armed Forces Medical Examiner, excluding those that were
      known to have been incapacitated before the crash and those that were known to
      have attempted to escape from the aircraft, collecting 100 "qualified" crash
      decedents. The incidence of control surface injuries was determined for both
      pilots and passengers. The sensitivity and specificity of control surface
      injuries were calculated by classifying the decedents into a 4-cell diagnostic
      matrix. The positive and negative predictive values for control surface injuries
      were also calculated. Injuries that met the published definitions of control
      surface injuries had high incidences in passengers, as well as pilots, giving the
      term control surface injury a diagnostically unacceptable sensitivity and
      specificity for indicating "a pilot attempting to control an aircraft." We offer
      caveats and refinements to the definition of these injuries that help to increase
      the sensitivity and specificity of this term.

PMID- 17525560
TI  - Fatal neurotoxic response to neuroleptic medications: case report and review of
      the literature.
AB  - Neuroleptic malignant syndrome (NMS) is a diagnosis of exclusion difficult to
      make due to a lack of pathognomonic features. Diagnosing NMS by postmortem
      examination becomes increasingly challenging when possible underlying brain
      pathology is obscured. The diagnosis is based on clinical history and laboratory
      findings. Autopsy and histologic findings, if any, usually are reflective of
      hyperthermia or complications (eg, aspiration pneumonia) of NMS. The authors
      describe a case of a 36-year-old Hispanic woman with a presumptive diagnosis of
      pseudoseizures, treated with various combinations of neuroleptic medications over
      a 6-week period prior to her sudden, unexpected, in-hospital death. Neuroleptic
      malignant syndrome is likely to have contributed to this patient's death.
      Confounding factors and medicolegal issues of a postmortem diagnosis of NMS are
      discussed.

PMID- 17525561
TI  - Fatal birth trauma due to an undiagnosed abdominal teratoma: case report and
      review of the literature.
AB  - The fetus is subjected to mechanical forces during labor and delivery, which may
      result in traumatic injuries. Such injuries include intracranial hemorrhage,
      spinal cord lesions, cephalhematoma, cranial or peripheral nerve palsies,
      intraabdominal organ rupture, or bony fractures. Risk for perinatal trauma and
      mortality is increased in primigravidas, multiple gestations, abnormal
      presentations, maternal-fetal disproportion, oligohydramnios, forceps or vacuum
      extractions, and internal version maneuvers. Very-low-birth-weight neonates
      (<1500 g) are at high risk due to ease of deformity of the cranium. Infants with
      certain congenital anomalies or pathologic processes that distort normal anatomy
      are also at increased risk, especially when a prenatal diagnosis is lacking. The
      authors present a case of a term gestation neonate who sustained a cervical spine
      dislocation fracture of C5-7, with subtotal transection of the spinal cord and
      resultant paralysis. The fetus was in vertex presentation, and a manual vaginal
      delivery was attempted. When the infant lodged in the birth canal following a
      difficult delivery of the head and arms, its enlarged abdomen was palpated, and
      the delivery was converted to an emergent cesarean section. The infant lived for
      3 days and then expired due to neurologic complications of trauma sustained
      during the attempted vaginal delivery. Autopsy revealed a previously undiagnosed
      intraabdominal immature teratoma. The pathology of teratomas, the most common
      neonatal tumor and occasionally implicated in cases of birth trauma, will be
      addressed, followed by a review of the literature concerning birth trauma.

PMID- 17525562
TI  - Is right coronary artery hypoplasia and sudden death an underdiagnosed
      association?
AB  - Determining whether hypoplasia of a coronary artery has caused or contributed to
      death is often complicated by an absence of histologic evidence of myocardial
      ischemia in the area of the heart supplied by the affected artery and also by the
      lack of data for assessing coronary artery size at autopsy. A 45-year-old woman
      is reported who collapsed and died and who was found at autopsy to have a
      dominant, small-caliber, right coronary artery, with acute and chronic ischemic
      changes in the posterior interventricular septum supplied by the diminutive
      vessel. This case provides evidence that small-caliber coronary arteries may be
      associated with a lethal outcome. Given the difficulties that may occur in
      determining whether there is a causal link between small coronary artery caliber
      and death, it is possible that this may be an underdiagnosed cause of sudden
      cardiac death, rather than a coincidental finding of minimal significance.

PMID- 17525563
TI  - Extensive and mutilating craniofacial trauma involving defleshing and
      decapitation: unusual features of fatal dog attacks in the young.
AB  - Four cases of fatal dog attacks are reported in 3 children aged 6, 10, and 11
      years and in an infant aged 3 weeks. The cases were all characterized by
      extensive and mutilative stripping of soft tissues from the face and scalp,
      progressing to decapitation in the infant. The attacks were highly focused,
      involving 2 dogs in all but 1 case, with the area of trauma localized to the
      craniofacial region. The injuries resembled those found after postmortem animal
      depredation. The involvement of more than 1 dog may account for the severity of
      the injuries due to "pack" behavior. Deaths were due to exsanguination, air
      embolism, and decapitation. Necropsy examination of the attacking dogs revealed
      tissues from the victims in 2 of the animals' stomachs. These cases demonstrate
      the vulnerability of infants and young children to fatal dog attacks, with an
      unusual concentration of severe injuries to the head regions. Necropsy of the
      canine assailant, with collaboration between pathologists and veterinarians, is
      an important part of such investigations as it may provide information helping to
      establish the identity and ownership of the animal, along with trace evidence
      confirming that the dog was involved in the attack.

PMID- 17525564
TI  - Verapamil toxicity: an unusual case report and review of the literature.
AB  - Verapamil blocks the rapid influx of calcium into the cardiac myocytes of the
      cardiac conduction system and smooth muscle of the vasculature, resulting in
      decreased myocardial contractility, prolonged conduction time, and vascular
      relaxation. A sustained-release form, verapamil SR (or ER), is available that
      contains higher levels of medication and requires only once-daily dosing. The
      majority of reported fatal cases of verapamil toxicity are due to massive,
      intentional overdoses. Herein, we present an unusual case of fatal verapamil SR
      toxicity in a 57-year-old female that resulted from accidental overdose of only 3
      tablets (720 mg), as witnessed by the decedent's daughter. In spite of the low
      dose ingested, the postmortem cardiac blood verapamil level was clearly toxic
      (6000 ng/mL, or 6 mg/L). Her preexisting medical conditions included
      hypercholesterolemia, hypertension, iron deficiency anemia, diabetes mellitus,
      and associated mild chronic renal failure. Complicating factors, which likely
      include the decedent's preexisting renal and cardiac disease, and a review of the
      available literature will be discussed.

PMID- 17525565
TI  - Sudden death due to central alveolar hypoventilation syndrome (Ondine's curse) in
      a 39-year-old woman with heterotopia of the inferior olive.
AB  - Failure of automatic involuntary respiration with preservation of voluntary
      respiratory drive (Ondine's curse) is a rare occurrence which has been reported
      following a variety of morphologic lesions near respiratory centers in the lower
      brainstem. We report the case of a 39-year-old woman with a syndrome of fulminant
      respiratory failure with features of Ondine's curse in whom neuropathologic
      examination disclosed a preexisting malformation of the lower brainstem, as well
      as acute local subarachnoid bleeding. Mechanisms in the present case are
      discussed and a review of similar cases published so far is given. The necessity
      of sound investigation, including neuropathologic studies in cases of sudden
      unexplained death, is underlined.

PMID- 17525566
TI  - Analysis of mitochondrial DNA from the teeth of a cadaver maintained in
      formaldehyde.
AB  - This was a case that brought great commotion to a university in the interior of
      Brazil since it was suspected that one of the human bodies used for teaching
      anatomy was a relative of one of the students. Analysis of fragments of
      hypervariable region 2 of mitochondrial DNA (mtDNA) was performed using a
      miniprimer set (MPS), indicating that there had been a mistake in evaluation by
      the student, reinforcing the need to base the process of human identification in
      technical parameters.

PMID- 17525567
TI  - Barrett esophagus and unexpected death.
AB  - Barrett esophagus is characterized by the presence of columnar mucosa in the
      lower esophagus in continuity with gastric mucosa. Complications include
      ulceration and adenocarcinoma. Although sudden and unexpected death is not a
      usual outcome, the case of a 63-year-old man is presented who died unexpectedly
      following perforation of an ulcerated Barrett esophagus, with development of an
      esophagopleural fistula. Sudden and/or unexpected death in individuals with
      Barrett esophagus may result from hemorrhage due to erosion into mural vessels,
      the aorta or heart, or from penetration into the pleural space, trachea, bronchi,
      and pericardial sac, with the development of tension pyopneumothorax, bronchial
      fistula, and mediastinitis. Ulceration of the lower esophagus at autopsy should
      prompt consideration of the possibility of a Barrett esophagus and initiate
      careful dissection/examination of the surrounding mediastinal tissues and
      vessels.

PMID- 17525568
TI  - Delay of clinical manifestation and medical malpractice in a serious vascular
      complication of proximal locked tibial nailing.
AB  - We are reporting on a case of complex lesion of the popliteal neurovascular
      bundle in a young woman, resulting from an operation for reduction and synthesis
      of a closed spiroid fracture of the mid-distal third of the left tibia by means
      of a Grosse-Kempf nail, with significant delay of clinical manifestation.
      Determining whether this is an "unavoidable complication" or "medical
      malpractice" is the target of the forensic investigation. In this case, the
      investigation leads to the conclusion that medical malpractice was the only
      explanation of the damage.

PMID- 17525569
TI  - Migration of a Kirschner wire used in the fixation of a subcapital humeral
      fracture, causing cardiac tamponade: case report and review of literature.
AB  - Metallic pins and wires are frequently used for fixation of fractures and
      dislocations. Migration is one of the potential complications of such fixation
      methods. Usually, migration of the pins causes only minor complications, but if
      the device migrates to a vital cavity, serious damage and even death may ensue.
      The shoulder girdle is one of the areas in which pins and wires are mostly used,
      the humeral neck fractures being one of them. We report a case in which a
      Kirschner wire migrated from a subcapital humeral fracture site into the aorta
      and pericardium, causing sudden cardiac tamponade and death.

PMID- 17525570
TI  - Elder neglect and the pathophysiology of aging.
AB  - Elder neglect, one of the 6 forms of elder maltreatment, is difficult to diagnose
      and is underreported both in the scientific literature and to law enforcement.
      Recognizing fatal neglect is even more challenging especially with concurrent
      organic disease. Many entities can mimic elder neglect, and many age-related
      changes can result in pathology that may be confused with maltreatment. We
      retrospectively reviewed all forensic cases of individuals age sixty-five years
      and older which were referred for autopsy. Cases of fatal neglect were analyzed
      as to age, sex, race, cause of death, location of incident, perpetrator, victim
      to-perpetrator relationship, and autopsy and ancillary findings. The cases
      studies totaled 8. The age range was 74 to 94 years. Two were white, 6 black, one
      male, and 7 female. The causes of death were sepsis due to severe decubitus
      ulcers and severe dehydration. Five cases occurred in the victim's home, and 3
      occurred in an institution (nursing home/care facility). In 5 cases, the
      perpetrators were family members. The pathophysiology of aging with respect to
      elder maltreatment is reviewed.

PMID- 17525571
TI  - Child sexual abuse: an Italian perspective.
AB  - The problem of child sexual abuse is a growing reality in Italy. The experience
      of over 200 children seen by the SVS (Soccorso Violenza Sessuale) Centre in Milan
      (the first Italian large-scale study) may give more information on the European
      situation. This study is a retrospective study based on information contained in
      the files of children beneath the age of 14 seen at the SVS Centre between May
      1996 and May 2003, who arrived with a suspicion of child sexual abuse. Over 80%
      of all cases fell within the normal-aspecific category according to Adams' 2001
      classification. This first Italian survey, though not based on substantiated
      cases but only on cases of suspected sexual abuse, supplies a perspective on a
      large northern European city such as Milan. Data seem similar to those published
      in other non-European studies, particularly as regards clinical signs observed.
      Thus, the results of this study, with all their limitations, start to give a
      perspective on the frequency and type of child population reaching this Italian
      center, what the scenarios are, what signs the children present and how
      infrequent it is to find clinical anogenital signs concerning for sexual abuse.

PMID- 17525572
TI  - Sickle cell lung disease and sudden death: a retrospective/prospective study of
      21 autopsy cases and literature review.
AB  - Sudden death in the setting of sickle cell lung disease (SCLD), is periodically
      seen in the practice of medical examiners. The goal of the present study was to
      identify the most common pathologic findings of SCLD associated with sudden or
      unexpected death. A retrospective/prospective review of 21 autopsy cases from
      sickle cell patients between 1990 and 2004 was performed. Review of medical
      records, autopsy reports, and H&E-stained slides of lung tissue was performed.
      Oil-Red-O and elastic staining of lung tissue were evaluated. All cases were
      screened for both acute and chronic forms of SCLD. Patients admitted for sickle
      cell pain crisis ranged in age from 8 months to 65 years. Fifteen out of 21 cases
      (71.4%) showed significant pulmonary pathology. The most frequent lung findings
      included pulmonary edema (47.6%), pulmonary thromboembolism (38.1%), fat emboli
      (33.3%), pulmonary hypertension, grades I-IV (33.3%), and microvascular occlusive
      thrombi (28.5%). Our study demonstrates higher-than-expected percentages of acute
      and chronic sickle cell-related lung injury such as fat embolism (33.3%) and
      pulmonary hypertension (33.3%), with right ventricular hypertrophy (33.3%).
      Therefore, we propose a simple and high-yield autopsy algorithm of ancillary
      procedures that should be applied on all known and suspected autopsy cases of
      sickle cell disease.

PMID- 17525573
TI  - Intracranial arteriovenous malformations presenting as sudden unexpected death: a
      report of 3 cases and review of the literature.
AB  - Intracranial arteriovenous malformations (AVMs) are cerebrovascular abnormalities
      due to maldevelopment of the regional capillary bed, producing lesions with
      arteriovenous shunting. AVMs may account for as many as 1% of all sudden deaths;
      however, case reports in the literature are exceedingly rare. We present 3 cases
      of sudden death due to hemorrhage of AVM and discuss the literature and the
      differential diagnosis in cases of sudden death due to intracranial hemorrhage.

PMID- 17525574
TI  - Forensic issues in cases of Diogenes syndrome.
AB  - Diogenes syndrome is a syndrome described in the clinical literature in elderly
      individuals characterized by social isolation and extreme squalor. A number of
      typical features are found in the forensic evaluation of these deaths as the
      cases usually initiate medicolegal investigations due to the circumstances and
      the lack of recorded medical histories. Examinations of the death scenes are
      often difficult as victim's houses are in a state of disrepair, with filth and
      clutter, and pet dogs may resent the intrusion of strangers. Bodies are often
      filthy, with parasitic infestations, and are often putrefied due to the social
      isolation of the deceased and the delay in the finding of the corpse. Bodies may
      be traumatized from postmortem animal depredation by rodents or pets (eg, cats,
      dogs), and injuries such as bruises and lacerations may be present from falls
      associated with terminal illnesses or alcoholism. Blood or putrefactive fluids
      may be spread throughout the house by pets. Treatable medical conditions are
      often present in advanced stages, and features of hypothermia may be found.
      Attending police may suspect robbery due to disarray of the house and homicide
      due to apparent "bleeding" around the body from purging of putrefactive fluids,
      injuries from falls, or postmortem animal activity and "blood stains" throughout
      the house from antemortem injuries and/or fluid spread by animals. Finally, the
      identification of the deceased may be compromised by decay and/or postmortem
      animal activity. Thus, in addition to having typical clinical manifestations,
      such individuals appear to form a distinct subset of forensic cases having
      characteristic death scene and autopsy features and presenting particular
      difficulties in postmortem evaluations.

PMID- 17525575
TI  - Craniofacial identification by comparison of antemortem and postmortem
      radiographs: two case reports dealing with burnt bodies.
AB  - Two cases of positive identification of burnt bodies by radiographic comparison
      are reported. They emphasize that antemortem radiographs of the head are an
      important but sometimes overlooked source of information which can frequently
      provide useful objective data for comparison purposes. A positive identification
      can easily be achieved by medical examiners through visual comparison of the
      antemortem with the postmortem cranial and facial structures, even of bodies
      severely damaged by fire. In these bodies the radiographs of the skull can
      graphically depict structures which are often unique to the individual, such as
      the frontal sinus pattern and the morphology of dental restorations. However, the
      process of identification through radiographs is appropriate only in burnt bodies
      in which antemortem radiographs of the alleged deceased are available for
      comparison and unique craniofacial structures are still present on the body in a
      well-preserved state or at least not completely destroyed by fire, depending on
      the extent of the burn injury. Matching of corresponding features seems
      preferable to other methods of personal identification such as skull-photo
      superimposition, morphometric analysis, and/or other computer-aided methods since
      these techniques need trained personnel, as well as expensive equipment which is
      not invariably available in the medical examiner's office or department of
      anthropology.

PMID- 17525577
TI  - Gene therapy for pain.

PMID- 17525578
TI  - Advancing perioperative prediction of cardiac risk after vascular surgery: does
      postoperative N-terminal pro-brain natriuretic peptide do the trick?

PMID- 17525579
TI  - Anesthesia-related maternal mortality: a pat on the back or a call to arms?

PMID- 17525580
TI  - At the threshold of noninvasive functional hemodynamic monitoring.

PMID- 17525581
TI  - Tidal volumes in patients with normal lungs: one for all or the less, the better?

PMID- 17525582
TI  - N-terminal pro-brain natriuretic peptide identifies patients at high risk for
      adverse cardiac outcome after vascular surgery.
AB  - BACKGROUND: Preoperative N-terminal pro-BNP (NT-proBNP) is independently
      associated with adverse cardiac outcome but does not anticipate the dynamic
      consequences of anesthesia and surgery. The authors hypothesized that a single
      postoperative NT-proBNP level provides additional prognostic information for in
      hospital and late cardiac events. METHODS: Two hundred eighteen patients
      scheduled to undergo vascular surgery were enrolled and followed up for 24-30
      months. Logistic regression and Cox proportional hazards model were performed to
      evaluate predictors of in-hospital and long-term cardiac outcome. The optimal
      discriminatory level of preoperative and postoperative NT-proBNP was determined
      by receiver operating characteristic analysis. RESULTS: During a median follow-up
      of 826 days, 44 patients (20%) experienced 51 cardiac events. Perioperatively,
      median NT-proBNP increased from 215 to 557 pg/ml (interquartile range, 83/457 to
      221/1178 pg/ml; P<0.001). The optimum discriminate threshold for preoperative and
      postoperative NT-proBNP was 280 pg/ml (95% confidence interval, 123-400) and 860
      pg/ml (95% confidence interval, 556-1,054), respectively. Adjusted for age,
      previous myocardial infarction, preoperative fibrinogen, creatinine, high
      sensitivity C-reactive protein, type, duration, and surgical complications, only
      postoperative NT-proBNP remained significantly associated with in-hospital
      (adjusted hazard ratio, 19.8; 95% confidence interval, 3.4-115) and long-term
      cardiac outcome (adjusted hazard ratio, 4.88; 95% confidence interval, 2.43
      9.81). CONCLUSION: A single postoperative NT-proBNP determination provides
      important additional prognostic information to preoperative levels and may
      support therapeutic decisions to prevent subsequent structural myocardial damage.

PMID- 17525583
TI  - A series of anesthesia-related maternal deaths in Michigan, 1985-2003.
AB  - BACKGROUND: Maternal Mortality Surveillance has been conducted by the State of
      Michigan since 1950, and anesthesia-related maternal deaths were most recently
      reviewed for the years 1972-1984. METHODS: Records for pregnancy-associated
      deaths between 1985 and 2003 were reviewed to identify 25 cases associated with a
      perioperative arrest or major anesthetic complication. Four obstetric
      anesthesiologists independently classified these cases, and disagreements were
      resolved by discussion. Precise definitions of anesthesia-related and anesthesia
      contributing maternal death were constructed. Anesthesia-related deaths were
      reviewed to identify the chain of medical errors or care management problems that
      contributed to each patient death. RESULTS: Of 855 pregnancy-associated deaths, 8
      were anesthesia-related and 7 were anesthesia-contributing. There were no deaths
      during induction of general anesthesia. Five resulted from hypoventilation or
      airway obstruction during emergence, extubation, or recovery. Lapses in either
      postoperative monitoring or anesthesiology supervision seemed to contribute to 5
      of the 8 anesthesia-related deaths. Other characteristics common to these cases
      included obesity (n=6) and African-American race (n=6). CONCLUSIONS: The 8
      anesthesia-related and seven anesthesia-contributing maternal deaths in Michigan
      between 1985 and 2003 illustrate three key points. First, all anesthesia-related
      deaths from airway obstruction or hypoventilation took place during emergence and
      recovery, not during the induction of general anesthesia. Second, system errors
      played a role in the majority of cases. Of concern, lapses in postoperative
      monitoring and inadequate supervision by an anesthesiologist seemed to contribute
      to more than half of the deaths. Finally, this report confirms previous work that
      obesity and African-American race are important risk factors for anesthesia
      related maternal mortality.

PMID- 17525584
TI  - Respiratory variations in pulse oximetry plethysmographic waveform amplitude to
      predict fluid responsiveness in the operating room.
AB  - BACKGROUND: Respiratory variations in pulse oximetry plethysmographic waveform
      amplitude (DeltaPOP) are related to respiratory variations in pulse pressure
      (DeltaPP) and are sensitive to changes in preload. The authors hypothesized that
      DeltaPOP can predict fluid responsiveness in mechanically ventilated patients
      during general anesthesia. METHODS: Twenty-five patients referred for cardiac
      surgery were studied after induction of general anesthesia. Hemodynamic data
      (cardiac index, central venous pressure, pulmonary capillary wedge pressure,
      DeltaPP, and DeltaPOP) were recorded before and after volume expansion (500 ml
      hetastarch, 6%). Fluid responsiveness was defined as an increase in cardiac index
      of 15% or greater. RESULTS: Volume expansion induced changes in cardiac index
      (2.0+/-0.4 to 2.3+/-0.5 mmHg; P<0.05), DeltaPP (11+/-7 to 6+/-5%; P<0.05), and
      DeltaPOP (12+/-9 to 7+/-5%; P<0.05). DeltaPOP and DeltaPP were higher in
      responders than in nonresponders (17+/-8 vs. 6+/-4 and 14+/-7 vs. 6+/-4%,
      respectively; P<0.05 for both). A DeltaPOP greater than 13% before volume
      expansion allowed discrimination between responders and nonresponders with 80%
      sensitivity and 90% specificity. There was a significant relation between
      DeltaPOP before volume expansion and percent change in cardiac index after volume
      expansion (r=0.62; P<0.05). CONCLUSIONS: DeltaPOP can predict fluid
      responsiveness noninvasively in mechanically ventilated patients during general
      anesthesia. This index has potential clinical applications.

PMID- 17525585
TI  - Incidence of chest tube malposition in the critically ill: a prospective computed
      tomography study.
AB  - BACKGROUND: Malposition of percutaneously inserted chest tubes is considered as a
      rare complication in critically ill patients. Its incidence, however, remains
      uncertain. The aims of the study were to assess the true incidence of chest tube
      malposition in critically ill patients and to identify predicting factors.
      METHODS: The authors prospectively studied 122 chest tubes percutaneously
      inserted in 75 consecutive critically ill patients. For clinical reasons
      independent of the study, thoracic computed tomography scanning was performed in
      63 patients, allowing direct visualization of 106 chest tubes. Based on these
      findings, chest tube position was classified as intrapleural, intrafissural, or
      intraparenchymal. Factors predicting chest tube malposition were analyzed by
      univariate and multivariate analysis. RESULTS: The mean delay between chest tube
      placement and thoracic scan was 3.5+/-2.9 days. Twenty-two chest tubes were
      diagnosed as being intrafissural (21%), and 10 were diagnosed as being
      intraparenchymal (9%). The only predicting factor associated with the risk of
      malposition was the use of a trocar for the percutaneous insertion of the chest
      tube (P=0.032). CONCLUSIONS: Malposition was detected in 30% of percutaneously
      inserted chest tubes, a higher incidence than previously reported. Avoiding the
      use of a trocar may reduce significantly the incidence of chest tube malposition.

PMID- 17525586
TI  - Volume replacement therapy during major orthopedic surgery using Voluven
      (hydroxyethyl starch 130/0.4) or hetastarch.
AB  - BACKGROUND: The purpose of this study was to test the equivalence of efficacy and
      compare the safety of the 6% hydroxyethyl starches (HES) Voluven (HES 130/0.4;
      Fresenius Kabi, Bad Homburg, Germany) and hetastarch (HES 670/0.75 in saline) for
      intravascular volume replacement therapy during major orthopedic surgery.
      METHODS: In a prospective, controlled, randomized, double-blind, multicenter
      trial of patients undergoing major orthopedic surgery, 49 patients were treated
      with HES 130/0.4 and 51 patients were treated with hetastarch. Infusion of
      colloids was guided by central venous and arterial blood pressures. The primary
      efficacy endpoint was the volume of colloid solution infused; the primary safety
      endpoints were calculated total erythrocyte loss, the nadir factor VIII activity,
      and the nadir von Willebrand factor concentration within 2 h of completion of
      surgery. RESULTS: The total volume of colloid solution required for
      intraoperative volume replacement did not differ between HES 130/0.4 and
      hetastarch (1,613+/-778 [SD] ml for HES 130/0.4 and 1,584+/-958 ml for
      hetastarch). The nadir factor VIII activity within 2 h of the end of surgery was
      lower for hetastarch than for HES 130/0.4 (P=0.0499); for those who received
      greater than 1,000 ml colloid, the nadir factor VIII activity and von Willebrand
      factor concentration within 2 h of end of surgery were lower for hetastarch than
      for HES 130/0.4 (P=0.0487 and P=0.008, respectively). CONCLUSION: Voluven (HES
      130/0.4) and hetastarch are equally efficacious plasma volume substitutes;
      however, HES 130/0.4 has a lesser effect on coagulation.

PMID- 17525587
TI  - Effects of xenon anesthesia on cerebral blood flow in humans: a positron emission
      tomography study.
AB  - BACKGROUND: Animal studies have demonstrated a strong neuroprotective property of
      xenon. Its usefulness in patients with cerebral pathology could be compromised by
      deleterious effects on regional cerebral blood flow (rCBF). METHODS: 15O-labeled
      water was used to determine rCBF in nine healthy male subjects at baseline and
      during 1 minimum alveolar concentration (MAC) of xenon (63%). Anesthesia was
      based solely on xenon. Absolute changes in rCBF were quantified using region-of
      interest analysis and voxel-based analysis. RESULTS: Mean arterial blood pressure
      and arterial partial pressure for carbon dioxide remained unchanged. The mean (+/
      SD) xenon concentration during anesthesia was 65.2+/-2.3%. Xenon anesthesia
      decreased absolute rCBF by 34.7+/-9.8% in the cerebellum (P<0.001), by 22.8+/
      10.4% in the thalamus (P=0.001), and by 16.2+/-6.2% in the parietal cortex
      (P<0.001). On average, xenon anesthesia decreased absolute rCBF by 11.2+/-8.6% in
      the gray matter (P=0.008). A 22.1+/-13.6% increase in rCBF was detected in the
      white matter (P=0.001). Whole-brain voxel-based analysis revealed widespread
      cortical reductions and increases in rCBF in the precentral and postcentral gyri.
      CONCLUSIONS: One MAC of xenon decreased rCBF in several areas studied. The
      greatest decreases were detected in the cerebellum, the thalamus and the cortical
      areas. Increases in rCBF were observed in the white matter and in the pre- and
      postcentral gyri. These results are in clear contradiction with ketamine, another
      N-methyl-D-aspartate antagonist and neuroprotectant, which induces a general
      increase in cerebral blood flow at anesthetic concentrations.

PMID- 17525588
TI  - Incidence of propofol infusion syndrome during noninvasive radiofrequency
      ablation for atrial flutter or fibrillation.
AB  - BACKGROUND: Propofol infusion syndrome is first manifest by unexplained metabolic
      acidosis. Its incidence is unknown. METHODS: Charts of all patients undergoing
      nonsurgical, catheter radiofrequency ablation for atrial flutter or fibrillation
      from 1999 through 2001 at Mayo Clinic Rochester, who received propofol and had an
      arterial blood gas drawn during the procedure, were reviewed retrospectively for
      metabolic acidosis, prospectively defined as base excess -2 or less. Of 301
      radiofrequency ablation cases, 55 had an arterial blood gas. Virtually all
      radiofrequency ablation patients received propofol, so they could not be used as
      nonpropofol controls. Instead, all carotid endarterectomy patients in 2000 who
      did not receive propofol and had an arterial blood gas drawn after anesthetic
      induction and before surgical incision were used as a comparator group. RESULTS:
      In propofol radiofrequency ablation patients with no apparent cause of metabolic
      acidosis besides propofol, 13 of 55 (24%) had base excess of -2 or less, versus
      22 of 267 carotid patients (8.2%) (P<0.01). Maximal negative base excess was 
      4.2+/-1.7 in these propofol patients and was not correlated with propofol dose,
      age, or fluid dose, versus base excess of -3.2+/-1.5 in carotid patients
      (P>0.05). Propofol patients received prolonged anesthetics (7 h) and high-dose
      propofol (20 mg/kg). CONCLUSIONS: This is the first incidence estimate of
      metabolic acidosis during prolonged propofol infusion and suggests that it is not
      rare. The study is limited by its retrospective nature and by the lack of
      baseline arterial blood gas data and will require confirmation by prospective
      study.

PMID- 17525589
TI  - Long-term effects of botulinum toxin on neuromuscular function.
AB  - BACKGROUND: Recent reports indicate increased incidence of Clostridium botulinum
      infections, particularly among drug abusers and tissue allograft recipients.
      Botulinum toxin also has potential application in biochemical warfare. The
      neurotoxin-induced paralysis often requires mechanical ventilation with and
      without muscle relaxants. The authors investigated the long-term effects of
      botulinum toxin on muscle function, expression of nicotinic acetylcholine
      receptors (nAChRs), and their interaction with muscle relaxant, atracurium.
      METHODS: Rats (n=30) were injected with varying doses (0.625, 2.5, and 10 U) of
      botulinum toxin into the tibialis muscle. Control animals (n=9) received an
      equivalent volume of saline. At 128 days after injection, neuromuscular function,
      pharmacodynamics of atracurium, and nAChRs were evaluated. RESULTS: Nerve-evoked
      tensions, including tetanic tension and muscle mass, were decreased on the toxin
      injected side in a dose-dependent manner relative to saline-injected controls as
      well as the contralateral side. Specific muscle tension and specific tetanic
      muscle tension (tensions/muscle mass) were not reduced. The ED10 of atracurium
      was reduced, the ED50 was unchanged, and the ED90 was increased in the highest
      (10-U) dose of toxin group. The atracurium plasma concentration to maintain a
      steady state 50% paralysis was significantly reduced in the 10-U toxin group. The
      nAChR concentrations in the tibialis muscle were significantly increased in a
      dose-dependent manner in all experimental groups. CONCLUSION: Botulinum toxin
      causes dose-dependent long-term neuromuscular changes. The loss of tension
      generating capacity is almost exclusively related to muscle atrophy, because the
      specific tension did not change. The decreased ED10, unaltered ED50, and
      increased ED90 to atracurium suggest its interactions with different isoforms of
      receptors having varying sensitivity to atracurium. The absence of fade, despite
      the persistent botulinum toxin-induced denervation (increased nAChRs), suggests
      that the up-regulated nAChRs may have compensated for the prejunctional effects
      of botulinum toxin.

PMID- 17525590
TI  - Cholinergic modulation of sevoflurane potency in cortical and spinal networks in
      vitro.
AB  - BACKGROUND: Victims of organophosphate intoxication with cholinergic crisis may
      have need for sedation and anesthesia, but little is known about how anesthetics
      work in these patients. Recent studies suggest that cholinergic stimulation
      impairs gamma-aminobutyric acid type A (GABAA) receptor function. Because GABAA
      receptors are major targets of general anesthetics, the authors investigated
      interactions between acetylcholine and sevoflurane in spinal and cortical
      networks. METHODS: Cultured spinal and cortical tissue slices were obtained from
      embryonic and newborn mice. Drug effects were assessed by extracellular voltage
      recordings of spontaneous action potential activity. RESULTS: Sevoflurane caused
      a concentration-dependent decrease in spontaneous action potential firing in
      spinal (EC50=0.17+/-0.02 mM) and cortical (EC50=0.29+/-0.01 mM) slices.
      Acetylcholine elevated neuronal excitation in both preparations and diminished
      the potency of sevoflurane in reducing action potential firing in cortical but
      not in spinal slices. This brain region-specific decrease in sevoflurane potency
      was mimicked by the specific GABAA receptor antagonist bicuculline, suggesting
      that (1) GABAA receptors are major molecular targets for sevoflurane in the
      cortex but not in the spinal cord and (2) acetylcholine impairs the efficacy of
      GABAA receptor-mediated inhibition. The latter hypothesis was supported by the
      finding that acetylcholine reduced the potency of etomidate in depressing
      cortical and spinal neurons. CONCLUSIONS: The authors raise the question whether
      cholinergic overstimulation decreases the efficacy of GABAA receptor function in
      patients with organophosphate intoxication, thereby compromising anesthetic
      effects that are mediated predominantly via these receptors such as sedation and
      hypnosis.

PMID- 17525591
TI  - Effects of vasopressin on microcirculatory blood flow in the gastrointestinal
      tract in anesthetized pigs in septic shock.
AB  - BACKGROUND: Vasopressin increases arterial pressure in septic shock even when
      alpha-adrenergic agonists fail. The authors studied the effects of vasopressin on
      microcirculatory blood flow in the entire gastrointestinal tract in anesthetized
      pigs during early septic shock. METHODS: Thirty-two pigs were intravenously
      anesthetized, mechanically ventilated, and randomly assigned to one of four
      groups (n=8 in each; full factorial design). Group S (sepsis) and group SV
      (sepsis-vasopressin) were made septic by fecal peritonitis. Group C and group V
      were nonseptic control groups. After 300 min, group V and group SV received
      intravenous infusion of 0.06 U.kg.h vasopressin. In all groups, cardiac index and
      superior mesenteric artery flow were measured. Microcirculatory blood flow was
      recorded with laser Doppler flowmetry in both mucosa and muscularis of the
      stomach, jejunum, and colon. RESULTS: While vasopressin significantly increased
      arterial pressure in group SV (P<0.05), superior mesenteric artery flow decreased
      by 51+/-16% (P<0.05). Systemic and mesenteric oxygen delivery and consumption
      decreased and oxygen extraction increased in the SV group. Effects on the
      microcirculation were very heterogeneous; flow decreased in the stomach mucosa
      (by 23+/-10%; P<0.05), in the stomach muscularis (by 48+/-16%; P<0.05), and in
      the jejunal mucosa (by 27+/-9%; P<0.05), whereas no significant changes were seen
      in the colon. CONCLUSION: Vasopressin decreased regional flow in the superior
      mesenteric artery and microcirculatory blood flow in the upper gastrointestinal
      tract. This reduction in flow and a concomitant increase in the jejunal mucosa-to
      arterial carbon dioxide gap suggest compromised mucosal blood flow in the upper
      gastrointestinal tract in septic pigs receiving low-dose vasopressin.

PMID- 17525592
TI  - Amnesic concentrations of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane
      (F6, 2N) and isoflurane alter hippocampal theta oscillations in vivo.
AB  - BACKGROUND: Drug-induced temporary amnesia is one of the principal goals of
      general anesthesia. The nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6,
      also termed 2N) impairs hippocampus-dependent learning at relative, i.e.,
      lipophilicity-corrected, concentrations similar to isoflurane. Hippocampal theta
      oscillations facilitate mnemonic processes in vivo and synaptic plasticity (a
      cellular model of memory) in vitro and are thought to represent a circuit level
      phenomenon that supports memory encoding. Therefore, the authors investigated the
      effects of F6 and isoflurane on theta oscillations (4-12 Hz). METHODS: Thirteen
      adult rats were implanted with multichannel depth electrodes to measure the
      microelectroencephalogram and were exposed to a range of concentrations of
      isoflurane and F6 spanning the concentrations that produce amnesia. Five of these
      animals also underwent control experiments without drug injection. The authors
      recorded the behavioral state and hippocampal field potentials. They confirmed
      the electrode location postmortem by histology. RESULTS: The tested
      concentrations for isoflurane and F6 ranged from 0.035% to 0.77% and from 0.5% to
      3.6%, respectively. Isoflurane increased the fraction of time that the animals
      remained immobile, consistent with sedation, whereas F6 had the opposite effect.
      Electroencephalographic power in the theta band was less when the animals were
      immobile than when they explored their environment. F6 suppressed the power of
      oscillations in the theta band. Isoflurane slowed theta oscillations without
      reducing total power in the theta band. CONCLUSIONS: Drug-induced changes in
      theta oscillations may be a common basis for amnesia produced by F6 and
      isoflurane. The different patterns suggest that these drugs alter network
      activity by acting on different molecular and/or cellular targets.

PMID- 17525593
TI  - Mutation of alpha1G T-type calcium channels in mice does not change anesthetic
      requirements for loss of the righting reflex and minimum alveolar concentration
      but delays the onset of anesthetic induction.
AB  - BACKGROUND: T-type calcium channels regulate neuronal membrane excitability and
      participate in a number of physiologic and pathologic processes in the central
      nervous system, including sleep and epileptic activity. Volatile anesthetics
      inhibit native and recombinant T-type calcium channels at concentrations
      comparable to those required to produce anesthesia. To determine whether T-type
      calcium channels are involved in the mechanisms of anesthetic action, the authors
      examined the effects of general anesthetics in mutant mice lacking alpha1G T-type
      calcium channels. METHODS: The hypnotic effects of volatile and intravenous
      anesthetics administered to mutant and C57BL/6 control mice were evaluated using
      the behavioral endpoint of loss of righting reflex. To investigate the
      immobilizing effects of volatile anesthetics in mice, the minimum alveolar
      concentration (MAC) values were determined using the tail-clamp method. RESULTS:
      The 50% effective concentration for loss of righting reflex and MAC values for
      volatile anesthetics were not altered after alpha1G channel knockout. However,
      mutant mice required significantly more time to develop anesthesia/hypnosis after
      exposure to isoflurane, halothane, and sevoflurane and after intraperitoneal
      administration of pentobarbital. CONCLUSIONS: The 50% effective concentration for
      loss of righting reflex and MAC values for the volatile anesthetics were not
      altered after alpha1G calcium channel knockout, indicating that normal
      functioning of alpha1G calcium channels is not required for the maintenance of
      anesthetic hypnosis and immobility. However, the timely induction of
      anesthesia/hypnosis by volatile anesthetic agents and some intravenous anesthetic
      agents may require the normal functioning of these channel subunits.

PMID- 17525594
TI  - Roles of amino acids and subunits in determining the inhibition of nicotinic
      acetylcholine receptors by competitive antagonists.
AB  - BACKGROUND: Binding sites for agonists and competitive antagonists
      (nondepolarizing neuromuscular blocking agents) are located at the alpha-delta
      and alpha-epsilon subunit interfaces of adult nicotinic acetylcholine receptors.
      Most information about the amino acids that participate in antagonist binding
      comes from binding studies with (+)-tubocurarine and metocurine. These bind
      selectively to the alpha-epsilon interface but are differentially sensitive to
      mutations. To test the generality of this observation, the authors measured
      current inhibition by five competitive antagonists on wild-type and mutant
      acetylcholine receptors. METHODS: HEK293 cells were transfected with wild-type or
      mutant (alphaY198F, epsilonD59A, epsilonD59N, epsilonD173A, epsilonD173N,
      deltaD180K) mouse muscle acetylcholine receptor complementary DNA. Outside-out
      patches were excised and perfused with acetylcholine in the absence and presence
      of antagonist. Concentration-response curves were constructed to determine
      antagonist IC50. An antagonist-removal protocol was used to determine
      dissociation and association rates. RESULTS: Effects of mutations were antagonist
      specific. alphaY198F decreased the IC50 of (+)-tubocurarine 10-fold, increased
      the IC50 of vecuronium 5-fold, and had smaller effects on other antagonists. (+)
      Tubocurarine was the most sensitive antagonist to epsilonD173 mutations.
      epsilonD59 mutations had large effects on metocurine and cisatracurium.
      deltaD180K decreased inhibition by pancuronium, vecuronium, and cisatracurium.
      Inhibition by these antagonists was increased for receptors containing two delta
      subunits but no epsilon subunit. Differences in IC50 arose from differences in
      both dissociation and association rates. CONCLUSION: Competitive antagonists
      exhibited different patterns of sensitivity to mutations. Except for pancuronium,
      the antagonists were sensitive to mutations at the alpha-epsilon interface.
      Pancuronium, vecuronium, and cisatracurium were selective for the alpha-delta
      interface. This suggests the possibility of synergistic inhibition by pairs of
      antagonists.

PMID- 17525595
TI  - Antihyperalgesic effect of a recombinant herpes virus encoding antisense for
      calcitonin gene-related peptide.
AB  - BACKGROUND: Calcitonin gene-related peptide (CGRP) is contained in and released
      by small-diameter, nociceptive primary afferent sensory neurons. Upon spinal
      release, one of the effects of CGRP seems to be to sensitize dorsal horn neurons
      to subsequent input from nociceptive afferents and, consequently, to induce a
      behavioral hyperalgesia. Therefore, attenuating evoked release of CGRP from
      central terminals of nociceptors should have an antihyperalgesic effect. METHODS:
      The authors applied a recombinant herpes vector, encoding an antisense sequence
      to the whole CGRP gene, to the dorsal surface of the hind paw of mice to knock
      down expression of the peptide selectively in primary afferents innervating this
      tissue. RESULTS: Herpes virus-based vector encoding an antisense sequence for the
      whole CGRP clearly reduced CGRP immunoreactivity in the infected spinal dorsal
      horn levels as well as in cultured dorsal root ganglia neurons. Selective
      knockdown of CGRP in primary afferents significantly attenuated the thermal, C
      fiber hyperalgesia normally observed after topical application of capsaicin. The
      effect of viral vector-mediated knockdown of CGRP was comparable to the effect of
      intrathecal application of the CGRP antagonist CGRP8-37, but lasted for 14 weeks
      after one single application. CONCLUSION: Viral vector-mediated knockdown of CGRP
      in primary afferent neurons provides a promising tool for treatment of chronic
      pain states as well as for studies investigating the pathophysiology underlying
      these conditions.

PMID- 17525596
TI  - Mechanical pain hypersensitivity after incisional surgery is enhanced in rats
      subjected to neonatal peripheral inflammation: effects of N-methyl-D-aspartate
      receptor antagonists.
AB  - BACKGROUND: Neonatal pain and inflammation may lead to a long-term effect on
      nociceptive processing in adults. The current study examined the characteristics
      of postoperative incisional pain behaviors in adult rats that were subjected to
      neonatal peripheral inflammation. METHODS: Rat pups received a subcutaneous
      injection of saline or carrageenan into the plantar surface of the left hind paw
      at postnatal day 1. Naive pups were used as the control. Paw withdrawal
      thresholds to punctuate mechanical stimuli were examined at postnatal days 35,
      42, and 49. After rats received a plantar incision on the left or right hind paw
      at postnatal day 50, paw withdrawal thresholds were measured at 4 h, 1 day, 2
      days, 3 days, 5 days, and 7 days after incision. In addition, spinal cord Fos
      expression was detected at 2 h after incision. Finally, the effects of
      intrathecal N-methyl-D-aspartate receptor antagonists DL-2-amino-5
      phosphonovaleric acid and dizocilpine and the nitric oxide synthase inhibitor L-N
      nitro-arginine methylester on incisional pain were examined at 4 h after
      incision. RESULTS: Although the rats subjected to neonatal peripheral carrageenan
      injection developed mechanical hypoalgesia in bilateral hind paws at baseline,
      they displayed increased spinal cord Fos expression at 2 h and exaggerated
      mechanical pain hypersensitivity at 4 h (but not at other time points) after
      plantar incision. Intrathecal DL-2-amino-5-phosphonovaleric acid, dizocilpine,
      and L-N-nitro-arginine methylester significantly attenuated incision-induced
      mechanical pain hypersensitivity at 4 h after incision in the neonatally
      carrageenan-treated rats, but not in the naive or neonatally saline-treated rats.
      CONCLUSIONS: The authors' results suggest that early inflammatory insults during
      the neonatal period could produce excessive incision-associated mechanical pain
      hypersensitivity in adult rats. Spinal cord N-methyl-D-aspartate receptors and
      downstream nitric oxide signaling might contribute to this abnormal pain
      hypersensitivity, although the mechanisms underlying the long-term effect of
      neonatal inflammation are still unclear.

PMID- 17525597
TI  - Oral gabapentin activates spinal cholinergic circuits to reduce hypersensitivity
      after peripheral nerve injury and interacts synergistically with oral donepezil.
AB  - BACKGROUND: Gabapentin administration into the brain of mice reduces nerve injury
      induced hypersensitivity and is blocked by intrathecal atropine and enhanced by
      intrathecal neostigmine. The authors tested the relevance of these findings to
      oral therapy by examining the efficacy of oral gabapentin to reduce
      hypersensitivity after nerve injury in rats and its interaction with the
      clinically used cholinesterase inhibitor, donepezil. METHODS: Male rats with
      hypersensitivity after spinal nerve ligation received gabapentin orally,
      intrathecally, and intracerebroventricularly with or without intrathecal
      atropine, and withdrawal threshold to paw pressure was determined. The effects of
      oral gabapentin and donepezil alone and in combination on withdrawal threshold
      were determined in an isobolographic design. RESULTS: Gabapentin reduced
      hypersensitivity to paw pressure by all routes of administration, and was more
      potent and with a quicker onset after intracerebroventricular than intrathecal
      injection. Intrathecal atropine reversed the effect of intracerebroventricular
      and oral gabapentin. Oral gabapentin and donepezil interacted in a strongly
      synergistic manner, with an observed efficacy at one tenth the predicted dose of
      an additive interaction. The gabapentin-donepezil combination was reversed by
      intrathecal atropine. CONCLUSIONS: Although gabapentin may relieve neuropathic
      pain by actions at many sites, these results suggest that its actions in the
      brain to cause spinal cholinergic activation predominate after oral
      administration. Side effects, particularly nausea, cannot be accurately
      determined on rats. Nevertheless, oral donepezil is well tolerated by patients in
      the treatment of Alzheimer dementia, and the current study provides the rationale
      for clinical study of combination of gabapentin and donepezil to treat
      neuropathic pain.

PMID- 17525598
TI  - Postoperative analgesic effects of continuous wound infiltration with diclofenac
      after elective cesarean delivery.
AB  - BACKGROUND: Postoperative pain mostly results from sensitization of afferent
      fibers at injury sites driving central sensitization. Recently, peripheral
      processes have gained attention as mechanisms of hyperalgesia, and prostaglandins
      are among highly sensitizing agents. To date, perioperative administration of a
      single local dose of nonsteroidal antiinflammatory drugs has shown inconclusive
      efficacy. Rather than a single bolus, the current study evaluates the
      postoperative analgesic effect of diclofenac continuous intrawound infusion after
      elective cesarean delivery. METHODS: Ninety-two parturients were randomly
      allocated to receive a 48-h continuous intrawound infusion with 240 ml containing
      300 mg diclofenac, 0.2% ropivacaine, or saline. In the ropivacaine and saline
      groups, patients also received 75 mg intravenous diclofenac every 12 h for 48 h.
      Postoperative evaluation included intravenous morphine consumption by patient
      controlled analgesia and visual analog pain scores. Punctate mechanical
      hyperalgesia surrounding the wound and presence of residual pain after 1 and 6
      months were also assessed. RESULTS: Continuous diclofenac infusion significantly
      reduced postoperative morphine consumption (18 mg; 95% confidence interval, 12.7
      22.2) in comparison with saline infusion and systemic diclofenac (38 mg; 95%
      confidence interval, 28.8-43.7) (P=0.0009) without unique adverse effects.
      Postoperative analgesia produced by local diclofenac infusion was as effective as
      local ropivacaine infusion with systemic diclofenac. CONCLUSIONS: After elective
      cesarean delivery, continuous intrawound infusion of diclofenac demonstrates a
      greater opioid-sparing effect and better postoperative analgesia than the same
      dose administered as an intermittent intravenous bolus.

PMID- 17525599
TI  - What tidal volumes should be used in patients without acute lung injury?
AB  - Mechanical ventilation practice has changed over the past few decades, with tidal
      volumes (VT) decreasing significantly, especially in patients with acute lung
      injury (ALI). Patients without acute lung injury are still ventilated with large-
      and perhaps too large--VT. Studies of ventilator-associated lung injury in
      subjects without ALI demonstrate inconsistent results. Retrospective clinical
      studies, however, suggest that the use of large VT favors the development of lung
      injury in these patients. Side effects associated with the use of lower VT in
      patients with ALI seem to be minimal. Assuming that this will be the case in
      patients without ALI/acute respiratory distress syndrome too, the authors suggest
      that the use of lower VT should be considered in all mechanically ventilated
      patients whether they have ALI or not. Prospective studies should be performed to
      evaluate optimal ventilator management strategies for patients without ALI.

PMID- 17525600
TI  - Sexual dreaming during anesthesia: early case histories (1849-1888) of the
      phenomenon.

PMID- 17525601
TI  - Prone positioning for a morbidly obese patient with acute respiratory distress
      syndrome: an opportunity to explore intrinsic positive end-expiratory pressure
      lower inflexion point interdependence.

PMID- 17525602
TI  - Naloxone-insensitive epidural placebo analgesia in a chronic pain patient.

PMID- 17525604
TI  - Role of presynaptic acetylcholine autoreceptors at motor nerve endings on tetanic
      and train-of-four fade seen during a nondepolarizing neuromuscular block.

PMID- 17525605
TI  - Ultrasound-guided intraneural injections and neurologic injury.

PMID- 17525606
TI  - Ultrasound detects intraneural injection.

PMID- 17525607
TI  - Intraneural injection of local anesthetics during ultrasound-guided peripheral
      nerve block may lead to nerve injury.

PMID- 17525608
TI  - Evidence of nerve puncture during ultrasound-guided peripheral nerve blocks.

PMID- 17525609
TI  - Prediction of a low success rate of astronauts in space in performing
      endotracheal intubation.

PMID- 17525612
TI  - Excessive crystalloid infusion may contribute to ischemic optic neuropathy.

PMID- 17525613
TI  - What happened to the old visual evoked potential monitoring?

PMID- 17525614
TI  - Visual loss after spinal surgery.

PMID- 17525617
TI  - Loss of gag reflex and swallowing ability after administration of intrathecal
      fentanyl.

PMID- 17525618
TI  - Treatment of supraglottic airway edema by local hyaluronidase.

PMID- 17525619
TI  - Airway obstruction due to cuff herniation of a classic reusable laryngeal mask
      airway.

PMID- 17525621
TI  - Editorial--a personal perspective.

PMID- 17525622
TI  - Recommendations for improved standardization of immunohistochemistry.
AB  - Immunohistochemistry (IHC) continues to suffer from variable consistency, poor
      reproducibility, quality assurance disparities, and the lack of standardization
      resulting in poor concordance, validation, and verification. This document lists
      the recommendations made by the Ad-Hoc Committee on Immunohistochemistry
      Standardization to address these deficiencies. Contributing factors were
      established to be underfixation and irregular fixation, use of nonformalin
      fixatives and ancillary fixation procedures divested from a deep and full
      understanding of the IHC assay parameters, minimal or absent IHC assay
      optimization and validation procedures, and lack of a standard system of
      interpretation and reporting. Definitions and detailed guidelines pertaining to
      these areas are provided.

PMID- 17525623
TI  - Geometry of human vascular system: is it an obstacle for quantifying
      antiangiogenic therapies?
AB  - It is now recognized that all human natural and diseased anatomic systems are
      characterized by irregular shapes and very complex behaviors. In geometrical
      terms, tumor vascularity (which is the result of a nonlinear dynamic process
      called angiogenesis) is an archetypal anatomic system that irregularly fills a 3
      dimensional Euclidean space. This characteristic, together with the highly
      variable nature of vessel shapes and surfaces, leads to considerable spatial and
      temporal heterogeneity in the delivery of oxygen, nutrients, and drugs, and the
      removal of metabolites. Although these biologic features have been well
      established, the quantitative analysis of neovascularity in 2-dimensional
      histologic sections still fails to view its architecture as a non-Euclidean
      geometrical object, thus allowing errors in visual interpretation and discordant
      results concerning the same tumor from different laboratories. We discuss here
      the tumor-induced vascular system as a fractal object, and what changes this new
      way of observing may bring to the quantification of effective antiangiogenic
      therapies.

PMID- 17525624
TI  - Evidence-based guidelines for the utilization of immunostains in diagnostic
      pathology: pulmonary adenocarcinoma versus mesothelioma.
AB  - There are no firmly established guidelines for the use of antibodies in
      immunohistology as individual tests or panels. Practicing pathologists must rely
      on information available in individual publications, review articles, books, and
      internet-based databases to develop diagnostic immunohistochemical algorithms for
      their individual practices. In contrast, other medical specialties have crafted
      many evidence-based practice guidelines (EBG) that are widely used; these have
      helped to augment standardization and cost effectiveness. In particular, the use
      of several "epithelial" and "mesothelial" antibodies has been proposed to
      distinguish epithelioid malignant mesothelioma from metastatic pulmonary
      adenocarcinoma. Other authors have previously done systematic literature reviews
      of this subject up through 2004 and integrated the results of 88 publications
      into summarized test-performance values for 15 preselected immunohistochemical
      markers. The results suggested that 7 tests provide optimal sensitivity and
      specificity (MOC-31, BG8, CEA, TTF-1, CK5/6, WT-1, and HBME-1), but they provide
      no guidance for integration of such data into EBG. Odds ratios (ORs) were
      employed to compare the effectiveness of any single test, and chosen combinations
      thereof, in the differential diagnosis of malignant mesothelioma and metastatic
      pulmonary adenocarcinoma. Surprisingly, selected single immunostains or antibody
      pairs yielded ORs (varying from 96.34 to 1233.19) that were equal or better in
      efficacy when compared with more comprehensive panels. These results support the
      potential value of systematic reviews, meta-analysis, and OR calculations for
      development of EBG in diagnostic immunohistology.

PMID- 17525625
TI  - Immunohistochemical staining of papillary breast lesions.
AB  - The separation of ductal papilloma from intraductal papillary carcinoma of the
      breast on hematoxylin and eosin stained sections often presents diagnostic
      difficulty. Immunohistochemical staining is often employed in diagnosis,
      historically with smooth muscle actin (SMA). In this study, the staining
      characteristics of a panel of myoepithelial markers (calponin, p63, P-cadherin),
      were compared with SMA, and the epithelial expression of CD44s was assessed in 99
      papillary lesions. SMA, calponin, and p63 demonstrated myoepithelial cells in
      61%, 63%, and 65% of papillary lesions, respectively. However, specificity was
      quite variable. Calponin-stained stromal myofibroblasts (35% of cases), vessel
      pericytes (92%), and endothelial cells (69%), though each to a lesser degree than
      SMA. Calponin also showed cross reactivity with epithelium in 18% of cases. p63
      was almost completely restricted to myoepithelial cell nuclei, and did not stain
      vascular smooth muscle or myofibroblasts. However, p63 stained the epithelial
      component in one papillary carcinoma, a basal layer of cells in 1 biphasic
      invasive carcinoma, and the cytoplasm in 1 case. P-cadherin stained both
      epithelial and myoepithelial cells. The epithelial expression of CD44s and did
      not distinguish papillomas from papillary carcinomas. Thus, P-cadherin and CD44s
      are not useful in the characterization of papillary lesions. Given increased
      specificity as compared with SMA, the combination of p63 and calponin is
      recommended for analysis of breast papillary lesions.

PMID- 17525626
TI  - Analysis of immunohistochemical markers in bone marrow sections to evaluate for
      myelodysplastic syndromes and acute myeloid leukemias.
AB  - BACKGROUND: Accurate bone marrow (BM) blast counts (BCs) are essential for
      diagnosis (dx) of myelodysplasia (MDS), MDS/myeloproliferative (MDS/MPD) disease,
      or acute myeloid leukemia (AML), and may be difficult in hemodiluted bone marrow
      aspirates (BMAs). Erythroid precursors (EPs) may be indistinguishable from
      myeloblasts in BM sections (aspirate clots/cores). We compare the usefulness of
      immunohistochemistry (IHC) [ie, CD34, CD117, myeloperoxidase (MPO), Hemoglobin A1
      (HbA1), and terminal deoxynucleotidyl transferase (TdT)] of BM sections (IHC-BM)
      with BMA, bone marrow touch preparation (BMTP), and flow cytometry (FC) BCs.
      DESIGN: The initial BC (48), percentage (%) of Eps (38) (both based on initial
      100 to 600-cell counts), and FC expressions of CD34, CD117, Glycophorin A(GLY A),
      and TdT (44) were tabulated from 50 BMs (MDS, MDS/MPD, or AML). BMAs (48) and
      BMTPs (25) subsequently received 500-cell counts. IHC-BM was performed
      (45:formalin, 5:B5-fixed) [CD34 (46), CD117 (45), HbA1 (45), TdT (42), and MPO
      (45)]. RESULTS: Retrospective BMA BCs revealed a 31% (15/48) discrepant rate
      between the original/retrospective BMA BCs; 80% revealed an underestimated
      initial BC. There was a 28% discordance rate between the retrospective BMA and
      BMTP reviews; 77% showed a higher BMTP BC. IHC showed significantly higher BCs in
      19% (9/47), resulting in a different dx (5). However, CD34 and CD117 IHCS
      revealed lower BCs in 38% and 48%, respectively. The CD34 IHC results were
      primarily due to CD34-negative blasts by FC. The CD117 IHC results were largely
      unexplained. EPs were CD34 and CD117-negative. CONCLUSIONS: (1) Evaluation for
      MDS/AML requires 500-cell counts of BMAs and/or BMTPs. (2) CD34 and/or CD117
      blasts by FC indicate IHC-BM may increase BC accuracy. (3) CD34 is more reliable
      than CD117 by IHC; however, in combination, they are most reliable and should be
      performed on BM clots/cores due to variable reactivity.

PMID- 17525627
TI  - The significance of Ki-67 proliferative index and cyclin D1 expression of
      dysplastic nevi in the biologic spectrum of melanocytic lesions.
AB  - Familial acquired dysplastic nevi carry a risk for the development of melanoma.
      However, the results in various studies regarding the significance of sporadic
      dysplastic nevi as a precursor of malignant melanoma (MM), are controversial. The
      aim of this study is to investigate cyclin D1 expression and Ki67 proliferative
      index in a group of melanocytic lesions to address the biologic significance of
      sporadic dysplastic nevi in the progression of melanocytic lesions. Formalin
      fixed paraffin-embedded material from 21 common melanocytic nevi, 42 dysplastic
      nevi, and 17 primary cutaneous MMs were examined. Standard streptavidin-biotin
      immunoperoxidase method was used for immunostaining with cyclin D1 and Ki-67
      antibody. Nuclear cyclin D1 immunostaining was scored and Ki-67 proliferative
      index was calculated. Cyclin D1 expression was significantly higher in melanoma
      than those in other lesions. However, there was no significant difference between
      dysplastic nevi and common melanocytic nevi in terms of cyclin D1 expression. Ki
      67 index was significantly higher in dysplastic nevi compared with common
      melanocytic nevi and to melanoma compared with dysplastic nevi. There was a
      significant positive correlation between cyclin D1 expression and Ki-67
      proliferative index for each group. The present study indicates significant
      differences in cyclin D1 expressions and Ki-67 indices among melanocytic lesions.
      We think that dysplastic nevi are biologically separate from common melanocytic
      nevi in terms of proliferative activity. Additionally, our results suggest that
      cyclin D1 expression may be related to malignant phenotype and is associated with
      high proliferation rate in MM.

PMID- 17525628
TI  - Metallothionein immunolocalization in actinic skin nonmelanoma carcinomas.
AB  - Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most
      frequent skin cancer. Its pathogeny is linked to genotoxic effects of actinic
      radiation exposure, especially to ultraviolet wavelength. Metallothionein (MT) is
      a low-molecular weight protein with high affinity for heavy metal. Its
      intracellular function has been related to heavy metals and free-radical
      detoxification, although many studies linked MT to protective action against
      actinic mutagenesis. In other way, overexpression in malignant tumors has been
      related to worse prognosis. We aimed to evaluate MT immunohistochemical
      expression in skin cancer associated to actinic radiation. Twenty-six BCC cases,
      20 SCC, and 6 normal skin fragments were investigated. Immunohistochemical assay
      were performed by streptavidin-biotin-peroxidase technique with standard
      monoclonal antibody (E9). In normal skin, immunostaining was observed in basal
      layer of the epithelium. In the epithelium adjacent to tumors, suprabasal layer
      was also intensely labeled. Mean MT immunostaining indices were 18.5+21.2% for
      BCC and 69.1+14.4% for SCC. This difference was statistically significant. Higher
      MT expression in SCC as compared with BCC suggests association with tumoral
      aggressiveness.

PMID- 17525629
TI  - The cytoskeletal proteins alpha-actinin, Ezrin, and talin are De-expressed in
      endometriosis and endometrioid carcinoma compared with normal uterine epithelium.
AB  - In this retrospective study on banked tissue, we found that alpha-actinin and
      talin were completely de-expressed in both endometriosis and endometrioid
      carcinoma tissue. Some patchy, depolarized labeling for ezrin was noted in the
      endometrioid carcinoma but not in endometriosis. The loss of these proteins in
      both endometriosis and endometrioid carcinoma tissue indicates a significant
      change in the integrity of these tissues compared with normal and the possibility
      that individual cells may break away from the parent histology due to loss of
      cell adhesion. It also indicates a similarity between endometrioid cancer and
      endometriosis with respect to epithelial cell function and adhesion.

PMID- 17525630
TI  - Alpha-methylacyl-CoA racemase/P504S overexpression in colorectal carcinoma is
      correlated with tumor differentiation.
AB  - Alpha-methylacyl-CoA racemase (AMACR)/P504S is an enzyme involved in the
      metabolism of branched-chain fatty acids. Little is known about correlation of
      AMACR expression with colorectal carcinoma (CRC) differentiation and prognosis.
      We investigated the expression of AMACR in 106 cases of primary CRC, and in 47
      lymph nodes with metastatic CRC by immunohistochemical analysis. These cases were
      divided into 3 groups according to the histologic differentiation of the primary
      tumors. group A included 50 cases of histologically well and moderately
      differentiated CRCs, 20 of these with lymph node metastasis; group B included 23
      cases of well and moderately differentiated CRCs, histologically similar to group
      A, except these tumors had small foci (less than 20%) of high-grade carcinoma,
      and 10 of these had lymph node metastasis; group C included 33 cases of poorly
      differentiated adenocarcinoma and undifferentiated carcinoma, 17 with lymph node
      metastasis. The results showed the overall positive rates of expression in
      primary and metastatic CRCs were 59.4% and 46.8%, respectively. Expression in
      groups A (76.0%) and B (69.6%) was much higher than that in group C (27.3%). In
      group B, although overexpression of AMACR in primary tumors was similar to that
      of group A, it was only seen in 30.0% of group B metastatic tumors, which was
      similar to the rate of expression in group C (23.5%). In contrast, rates of
      expression in group A primary and metastatic tumors were similar (80.0% and
      75.0%). Positive staining for AMACR in benign epithelium adjacent to tumor was
      rare (<2%). No relation was found between AMACR expression and overall survival.
      Our findings support the view that the expression of AMACR in CRC is correlated
      with tumor differentiation.

PMID- 17525631
TI  - Association of MYCN amplification and 1p deletion in neuroblastomas with high
      tumor vascularity.
AB  - The biologic behavior of neuroblastoma (NB) is extremely variable; therefore, the
      clinical behavior may be reliably predicted based on the analysis of a panel of
      prognostic parameters. High vascular density has been correlated with aggressive
      tumor progression in many types of cancers. The goal of this study was to
      correlate the tumor vascularity in NB with status of MYCN and the short arm of
      chromosome 1 (1p) to address the association between angiogenesis and genetic
      markers of prognostic significance. The study population consisted of 33 patients
      with histologically proven diagnosis of primary NB and no history of previous
      chemotherapy. Histologic quantitation of tumor angiogenesis was performed using 3
      different methods: microvessel density, vascular grading, and Chalkley counting.
      MYCN amplification and 1p deletion were determined by using fluorescence in situ
      hybridization technique. The differentiation and mitosis-karyorrhexis index of
      tumor cells were also assessed using the Shimada System. MYCN amplification was
      present in 12 cases (36.3%), and 1p deletion in 16 (48.5%). Both genetic changes
      significantly correlated with increased tumor vascularity. In addition, tumor
      vascularity was significantly increased in tumors with high mitosis-karyorrhexis
      index or of undifferentiated histology. We conclude that angiogenesis shows close
      association with histologic and genetic prognosticators in NB. Our data support
      the validity of recent applications of antiangiogenic agents which interfere or
      block NB progression.

PMID- 17525632
TI  - Cyclooxygenase-2 (COX-2) overexpression in meningiomas: real time PCR and
      immunohistochemistry.
AB  - Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme involved in the
      first steps of the prostaglandins and thromboxane synthesis. COX-2 up-regulation
      is demonstrated in tumors where it can modulate tumoral progression, metastasis,
      multidrug resistance, and angiogenesis. Experimental data suggest a possible
      therapeutic use of the COX-inhibitors nonsteroidal antiinflammatory drugs
      (NSAIDs). NSAIDs can block tumor growth through many mechanisms, especially
      through antiangiogenic and proapoptotic effects. Moreover, NSAIDs can also
      improve the efficacy of radiotherapy, chemotherapy, and hormonal therapy. This
      study reviews the COX-2 expression as evaluated through immunohistochemistry and
      real time polymerase chain reaction (RT-PCR) in 23 meningiomas [14 World Health
      Organization (WHO) grade I; 5 WHO grade II; 3 WHO grade III; 1 oncocytic
      meningioma]. At immunohistochemistry all the lesions but 4 (83%) were COX-2
      positive. At RT-PCR 9 meningiomas, 8 WHO grade I and 1 WHO grade II, showed a COX
      2 expression greater than the reference value (average expression of all
      meningiomas that we studied). The association between tumor grade and
      immunohistochemical or RT-PCR COX-2 expression was not significant (P=0.427 and
      P=0.251, respectively). In conclusion, even if further studies on larger series
      are necessary, the common COX-2 overexpression in meningiomas may suggest
      considering the COX-2 inhibitors, alone or in combination with radiotherapy, a
      potential area of therapeutic intervention in some selected meningiomas.

PMID- 17525633
TI  - Expression of the water channel protein aquaporin-9 in malignant brain tumors.
AB  - Recently, many studies seen concerning the expression and distribution of
      aquaporins and K channels in the central nervous system, and their physiological
      and pathophysiologic roles in water and ion homeostasis. Whereas most data were
      collected on aquaporin-4 (AQP4) in astrocytes, only little attention was paid to
      AQP9 which is a water channel transporting glycerol, mannitol, and urea as well.
      This is the first study describing AQP9 in human brain and human brain tumors.
      For comparison, we also investigated the immunohistochemical distribution of AQP9
      in the rat glioma RG2. Whereas in the normal rat brain AQP9 is only weakly
      expressed by astrocytes, the anti-AQP9 immunoreactivity was found to be increased
      at the tumor border, but not within the tumor. In contrast, in human
      glioblastoma, most glioma cells throughout the tumor revealed a strong anti-AQP9
      immunoreactivity across the whole surface of the cell. In the discussion, the
      increase of the anti-AQP9 immunoreactivity in glioma cells is suggested to
      reflect an upregulation and to counteract the glioma-associated lactic acidosis
      by clearance of glycerol and lactate from the extracellular space. In addition,
      the increased level of AQP9 immunoreactivity could be involved in the energy
      metabolism of the glioma and/or surrounding neuronal cells.

PMID- 17525634
TI  - Immunoperoxidase in the interpretation of discordant histologic and urease
      findings for Helicobacter pylori.
AB  - Azure A and methylene blue ("Diff-Quik," DQ) and tissue urease (U) tests are
      popular methods to diagnose Helicobacter pylori. These tests usually correlate
      well but sometimes produce discordant results. This study evaluates the DQ and U
      tests by comparing them with the immunoperoxidase reference method to resolve
      discordant results. DQ and U tests were performed on gastric biopsies. Results
      were tabulated as DQ(+)/U(+), DQ(+)/U(-), DQ(-)/U(+), and DQ(-)/U(-). Cases that
      were DQ(+)/U(+) were recorded as positive and not tested with immunoperoxidase.
      Cases that had discordant DQ/U results were tested by immunoperoxidase to resolve
      the discordance. Cases which were negative for both DQ/U were evaluated by
      immunoperoxidase to confirm the validity of DQ(1-)/U(-). The groups were compared
      with concordant results (DQ(1-)/U(-) group) and immunoperoxidase versus
      discordant DQ/U results and immunoperoxidase. There were 56 gastric biopsy
      specimens. Among all cases, 6 were DQ(+)/U(+). Of the remaining 50 cases, 38 were
      concordant DQ(-)/U(-), whereas 12 showed discordant DQ/U results. All 38
      concordant DQ(-)/U(-) specimens were confirmed negative, 11 discordant DQ/U cases
      were confirmed negative, and 1 DQ(+)/U(-) specimen was confirmed positive by
      immunoperoxidase. Comparison of concordant versus discordant results was not
      statistically significant (P=0.10). Among all discordant DQ and U, 11/12 (92%)
      were confirmed negative by immunoperoxidase. Thus, both concordant negative
      results and discordant results can be considered negative. Such interpretation of
      discordant results might prevent unnecessary additional procedures or treatment.

PMID- 17525635
TI  - Estrogen receptor antibody incubation time and extent of immunoreactivity in
      invasive carcinoma of the breast: the importance of optimizing antibody avidity.
AB  - We noticed that the percentage and intensity of estrogen receptor (ER) antibody
      (Ab) AB ER 1D5 immunohistochemical (IHC) staining was altered by Ab incubation
      time and the type of chromogen detection system in invasive breast carcinomas. We
      studied the impact of these 2 factors on Ab ER 1D5 immunoreactivity. Serial
      sections from 22 strongly ER-positive invasive breast carcinomas were
      immunohistochemically stained with Ab clone ER 1D5 using 3 IHC protocols. One IHC
      protocol used a 12-hour Ab incubation and a supersensitive, labeled streptavidin
      biotin chromogen detection system (12 h-Standard), the second IHC protocol used a
      2-hour Ab incubation and a supersensitive, labeled streptavidin-biotin chromogen
      detection system (2 h-SS), and the third protocol used a 2-hour Ab incubation and
      a polymer-based detection system (2 h-Env). Twenty identical fields on each slide
      stained with each IHC protocol were evaluated and staining was quantified using
      image analysis. The mean staining percentages using the 12 h-Standard, 2 h-SS,
      and 2 h-Env IHC staining protocols were 89%, 72%, and 47%, respectively
      (P<0.001). Three of the 22 cases (14%) were ER negative (<10% stained area) with
      the 2 h-Env IHC protocol. Stain intensity was significantly stronger with the 12
      h-Standard Ab incubation IHC protocol than either 2-hour Ab incubation protocol
      (P<0.001). Twelve cases stained with 2-hour Ab incubation IHC protocols had weak
      visually seen staining: 7 were Allred total score 2 (ER negative) and 5 were
      Allred total score 3. Ab ER 1D5 avidity is directly related to factors that
      impact electrostatic forces, one of which is Ab incubation time. Standard
      automated stainer Ab incubation times of less than 1 hour may be of insufficient
      duration and result in artificially low levels of ER immunoreactivity. The
      chromogen detection system in association with the ER 1D5 Ab also alters levels
      of immunoreactivity. Optimization of IHC staining protocols should include
      evaluating the Ab incubation time and chromogen detection system. These factors
      can substantially alter the extent and intensity of ER IHC staining.

PMID- 17525636
TI  - Pretreatment for immunohistochemical staining simplified.
AB  - This investigation compared several procedures for the pretreatment of formalin
      fixed and paraffin-embedded tissue sections before their immunohistochemical
      staining. The results showed that a simpler approach than what is traditionally
      being practiced today is possible and deserving of wider use as it not only
      shortens the total assay time but may also contribute to further the ongoing
      attempts to standardize immunohistochemistry. A detailed description of the
      method of choice is being given. Also included is an evaluation of several
      commercial reagents that are presently being promoted for the simultaneous
      deparaffinization, rehydration, and antigen retrieval.

PMID- 17525637
TI  - Immunohistochemical evaluation of H-R3 a novel humanized monoclonal antibody that
      neutralizes the EGF-receptor.
AB  - The epidermal growth factor receptor (EGF-R) is an important growth regulator of
      epithelial cancer cells, overexpressed by several human tumors and scantly
      detectable in most normal tissues. The introduction of monoclonal antibodies
      (Mabs) and more recently engineered humanized Mabs have greatly expanded the
      therapeutic potential of this modality of cancer treatment. The present study was
      designed to compare the specificity of the murine and humanized anti-EGF-R Mabs.
      Biotinylated Mabs were tested in samples of fetal and adult normal and neoplastic
      tissues by ABC peroxidase method. All fetal tissues studied were positive for
      both Mabs, showing 2 different staining patterns, one homogeneous and finely
      granular in cytoplasm and another grosser with intense labeling in both membrane
      and cytoplasm. A similar recognition pattern was exhibited in adult normal
      tissues, where an intense reactivity was also evidenced in skin, tongue,
      gastrointestinal tract, renal tubules, and breast gland epithelium. In tissues
      from genitourinary and central nervous system, a faint staining was demonstrate,
      whereas those from cardiovascular and lymphoid tissues proved to be negative.
      These Mabs exhibited a heterogeneous and strong membrane and cytoplasm staining
      in neoplastic cells from lung, breast, and head and neck cancer. On the basis of
      these results, we conclude that the humanized (h-R3) and murine (egf/r3) anti-EGF
      R Mabs show a very similar immunohistochemical pattern of recognition of fetal,
      adult, and neoplastic tissues. Also h-R3 Mab is a novel candidate for the
      development of an immunotherapeutic approach suitable for the treatment of tumors
      with EGF-R overexpression.

PMID- 17525638
TI  - Cell membrane reactivity of MIB-1 antibody to Ki67 in human tumors: fact or
      artifact?
AB  - Ki67 immunohistochemistry is a widely used marker of the tumor proliferative
      fraction. Apart from the nuclear staining of dividing cells, MIB-1 monoclonal
      antibody was also found to stain the cell membrane of some tumor types. Indeed,
      such membrane reactivity was proposed as a diagnostic feature of hyalinizing
      trabecular tumor (HTT) of the thyroid. To verify the diagnostic role of Ki67
      membrane pattern, 6 HTTs, 8 pulmonary sclerosing hemangiomas (SH), and 6 other
      human tumors with MIB-1 cell membrane immunoreactivity were stained by
      immunoperoxidase with 5 different anti-Ki67 antibodies in different experimental
      conditions. We show here that the cell membrane reactivity reported in HTT is
      produced only by MIB-1 and not by other antibodies to Ki67 (including
      commercially available mouse and rabbit monoclonal antibodies). In addition, this
      peculiar pattern is obtained only if the reaction is performed at room
      temperature, because automated immunostainers which operate at 37 degrees C do
      not produce any MIB-1 membrane localization. The same findings were obtained in
      the other 6 tumors. Conversely, sclerosing hemangioma of the lung did not produce
      any MIB-1 cell membrane reactivity in our hands. A cross-reactivity of the MIB-1
      monoclonal antibody with an epitope expressed at the cell membrane level (rather
      than an artifact) seems the most likely explanation for this finding, because the
      immunoreactivity is generally intense and uniform in the membrane positive
      tumors. We conclude that when Ki67 immunohistochemistry is used for diagnostic
      purposes in a suspected HTT, only MIB-1 clone at room temperature should be
      employed.

PMID- 17525639
TI  - Helicobacter pylori-induced changes in the gastric mucosa are associated with
      mitogen-activated protein kinase (MAPK) activation.
AB  - BACKGROUND: Gastric cancers are usually associated with and preceded by
      Helicobacter pylori (HP) infection, gastric atrophy, intestinal metaplasia, and
      dysplasia. HP infection alters cell kinetics of the gastric mucosa. Both
      proliferation and apoptosis are increased. Proinflammatory cytokines are
      responsible for some of these alterations. The mitogen-activated protein kinase
      (MAPK) signaling pathway has been implicated as a causative factor in these
      alterations based on in vitro studies. In this study, we investigated the effects
      of HP infection on gastric mucosal proliferation, apoptotic mechanisms, and the
      activation status of the MAPK signaling pathway at various stages of gastric
      carcinogenesis, especially intestinal metaplasia and dysplasia caused by HP
      infection. DESIGN: Stomach biopsies representing normal (n=20), HP+ (n=25), HP+
      with intestinal metaplasia (n=25), HP+ with dysplasia (n=15) and gastric
      adenocarcinoma (n=30; 20 HP+ and 10 HP-) cases were selected. Cell proliferation
      was assessed by proliferating cell nuclear antigen immunostaining. Apoptosis and
      survival-related markers; cleaved caspase-3, and phospho-MAPK extracellular
      signal-regulated kinase (ERK) were detected by immunohistochemical methods.
      RESULTS: Proliferation index (proliferating cell nuclear antigen) and cleaved
      caspase-3 expression were higher in the HP+, HP+ with intestinal metaplasia, and
      HP+ with dysplasia groups than in normal controls (P<0.05). Cleaved caspase-3
      activity was also high in the adenocarcinomas. Phospho-MAPK(ERK) expression was
      increased in the HP+, HP+ with intestinal metaplasia, HP+ with dysplasia and
      adenocarcinomas compared with the normal control group. Whereas HP- gastric
      carcinomas had a lower expression of phospho-MAPK. CONCLUSIONS: HP infection
      increases the proliferative rate of gastric foveolar cells in conjunction with an
      increased apoptotic rate and activation of MAPK(ERK). MAPK activation seems to be
      a significant and persistent event in the HP-induced neoplastic transformation.

PMID- 17525640
TI  - Assessment of cell proliferation in benign, premalignant and malignant skin
      lesions.
AB  - A deeper understanding of the variance of epidermal cell proliferation may
      eventually increase the reproducibility of diagnostic classification. A
      prospective study of 46 consecutive, unselected biopsies from benign
      (keratoacanthoma n=14), premalignant (actinic keratosis n=15 and Bowen disease
      n=10) and malignant (squamous cell carcinoma n=7) skin lesions was studied to
      assess the presence and extent of differences in expression of the proliferation
      marker Ki-67 using a monoclonal antibody directed against a c-DNA defined
      subsegment (MIB-1) and a noncross-linking, proprietary fixative BoonFix. MIB-1
      was expressed in the adjacent, non-affected skin in a scattered to confluent
      linear pattern in the basal/suprabasal cell layer. In actinic keratosis, MIB-1
      expression, in addition to basal/suprabasal layers, extended to mid-zones of the
      epidermis. An interesting feature in actinic keratosis as well as in Bowen
      disease was the expression of MIB-1 in the epithelium lining the hair follicles.
      In Bowen disease, MIB-1 was observed throughout the full thickness of the
      epidermis, unequivocally separating this entity from others under study. In
      invasive squamous cell carcinoma, MIB-1 expression was not consistent between and
      within cases. MIB-1 positivity was variably found in all layers of the epidermis,
      but showed a chaotic and haphazard pattern with total loss of polarity.
      Keratoacanthoma cases showed highly variable MIB-1 expression, ranging from no
      expression to expression in both basal/suprabasal and mid-zone layers of the
      epidermis. These results warrant further study of modulation of cell
      proliferation in actinic keratosis.

PMID- 17525641
TI  - Aberrant leukocyte common antigen expression in metastatic small cell lung
      carcinoma: a rare finding and a potential diagnostic pitfall.

PMID- 17525642
TI  - Endothelial keratoplasty using donor tissue not suitable for full-thickness
      penetrating keratoplasty.
AB  - PURPOSE: To evaluate the use of corneal donor tissue deemed unsuitable for full
      thickness penetrating keratoplasty (PK) for use in deep lamellar endothelial
      keratoplasty (DLEK) and to compare postoperative results to those of DLEK surgery
      using donor tissue that is suitable for PK. METHODS: Small-incision DLEK surgery
      was performed using 39 donor corneas unsuitable for PK. Thirty-five donors had
      anterior scars or opacities, 3 donors had pterygia within the 8-mm zone, and 1
      had prior LASIK. All donor preparation was completed by manual stromal
      dissection. The DLEK surgical and postoperative courses were reviewed.
      Preoperative and 6-month postoperative results of this study group were compared
      with a control group consisting of the first 55 consecutive small-incision DLEK
      patients receiving donor corneas that had no criteria excluding them from use in
      PK. Four eyes in the study group and 1 eye in the control group had the
      confounding variables of the presence of an anterior-chamber lens or surgical
      vitrectomy with macular disease in the recipient eye. RESULTS: There was no
      significant difference in preoperative measurements of best spectacle-corrected
      visual acuity (BSCVA; P = 0.372), donor endothelial cell density (ECD; P =
      0.749), or corneal topography [surface regularity index (SRI), P = 0.485; or
      surface asymmetry index (SAI), P = 0.154] between the 2 groups. For the patients
      receiving corneas deemed unacceptable for PK, at 6 months after surgery, the
      vision (P = 0.002) and corneal topography measurements improved significantly
      from before surgery (SRI, P < 0.001; SAI, P < 0.001), and there was no
      significant change in refractive astigmatism (P = 0.240). There was a significant
      difference in the vision at 6 months postoperatively between the overall study
      group and the control group, with the mean vision of the study group at 20/56 and
      the control group at 20/43 (P = 0.015). If eyes with known cystoid macular edema
      (CME) and vitrectomy are removed from each group, there is no significant
      difference in vision at 6 months between the study group and the control group (P
      = 0.110), with the average BSCVA of those receiving donor corneas unsuitable for
      PK equal to 20/48 (range, 20/25-20/200) and the average vision for those
      receiving PK-acceptable donor tissue equal to 20/43 (range, 20/20-20/80). The 6
      month average refractive astigmatism of the study group was 1.12 +/- 0.99 D
      (range, 0.00-4.00 D), and the average endothelial cell count was 2064 +/- 396
      cells/mm(2) (range, 1208-2957 cells/mm(2)). There was no significant difference
      in 6-month postoperative endothelial cell count (P = 0.443), refractive
      astigmatism (P = 0.567), or corneal topography (SRI, P = 0.332; SAI, P = 0.110)
      in study patients who received corneas unsuitable for PK compared with control
      patients who received corneas suitable for PK. CONCLUSIONS: Endothelial
      keratoplasty such as DLEK surgery with manual donor preparation broadens the
      donor pool by enabling corneas that cannot be used for PK to be used for
      selective endothelial transplantation without deleterious postoperative results.

PMID- 17525643
TI  - Factors affecting corneal endothelial morphology.
AB  - PURPOSE: To study the effects of age, race, years of contact lens wear, and
      degree of myopia on endothelial cell density, the coefficient of variation, and
      the percentage of hexagonal cells. METHODS: A total of 149 subjects with a broad
      variation in age (19 to 71 years), refractive error (39.6% had myopia over -5.00
      D), and contact lens history (13.4% had >20 years of wear) were examined. Most
      subjects were white, but one third were Asian. The Konan specular microscope was
      used to capture images from 1 eye of each subject and analyzed with the KSS-300
      software. Multiple regression analysis was used to build models of endothelial
      cell density, polymegathism, and pleomorphism. RESULTS: Age and race
      significantly affected endothelial cell density (ECD = 3274 - 12.7 x Age + [164
      if Asian]). Years of contact lens wear, age, and their interaction significantly
      affected coefficient of variation (CoV = 24.3 + 0.72 x CLyears + 0.18 x Age -
      0.011 x interaction). Years of contact lens wear, age, and refractive error all
      independently affected the percentage of hexagonal cells (% Hex = 70 - 0.29 x
      CLyears - 0.21 x Age + 0.4 x Rx). CONCLUSIONS: The three key aspects of corneal
      endothelial morphology are influenced by different factors. Any impact of contact
      lens wear on endothelial cell density may be caused by the confounding effect of
      age, and refractive error was associated with the percentage of hexagonal cells.
      Therefore, in studying the influence of drugs, devices, or disease, it is
      important to control for several subject-related factors.

PMID- 17525644
TI  - Corneal wound dehiscence after penetrating keratoplasty.
AB  - PURPOSE: To describe the clinical features of corneal wound dehiscence after
      penetrating keratoplasty (PK) after trauma and suture removal. METHODS: A
      retrospective review of all eyes needing resuturing in the 5-year period of July
      2000 to June 2005 was performed. In total, 76 eyes of 76 patients needed wound
      resuturing. The indications were early wound leak, wound dehiscence, broken
      suture, or loose suture. In 29 of the 76 cases, the indication for resuturing
      after PK was wound dehiscence. Of these, 19 were caused by trauma, and in 10
      eyes, dehiscence shortly followed suture removal. RESULTS: The interval between
      original PK and traumatic wound dehiscence caused by trauma ranged from 15 days
      to 33 years. In 5 eyes, it was >15 years. Nine eyes (47%) with traumatic
      dehiscence had final visual acuity better than 6/60, whereas 8 eyes (80%) with
      suture removal dehiscence had final visual acuity better than 6/18. Most of the
      dehiscence in the traumatic group was located in the inferior 2 quadrants, in
      contrast to temporally in the postsuture removal group. The time interval between
      PK and suture removal in the postsuture removal group was 16 +/- 4 months, and 7
      (70%) patients had a continuous suture. Post-suture removal dehiscence was more
      common when corneal edema was the indication for grafting. CONCLUSIONS: Eyes with
      traumatic wound dehiscence have worse visual outcome than those with dehiscence
      after suture removal. Patients should be cautioned about the risks and
      consequences of wound dehiscence. The suture may be left in place longer in older
      patients or when corneal edema is the indication for grafting.

PMID- 17525645
TI  - Five-millimeter-incision deep lamellar endothelial keratoplasty: one-year
      results.
AB  - PURPOSE: To evaluate visual acuity, topography, and endothelial cell density 1
      year after deep lamellar endothelial keratoplasty (DLEK) for endothelial
      dysfunction. METHODS: This is a prospective, comparative, interventional case
      series. Thirty-five eyes of 35 patients who had undergone DLEK with a 5-mm
      incision and had a minimum of 1-year follow-up were included. Main outcome
      measures were best spectacle-corrected visual acuity (BSCVA), uncorrected visual
      acuity (UCVA), astigmatism, topographic regularity and symmetry, and endothelial
      cell density. RESULTS: : One year postoperatively, BSCVA was 0.33 +/- 0.12 (mean,
      20/60; range, 20/40-20/400) compared with 0.15 +/- 0.15 preoperatively (mean,
      20/200; range, 20/70-20/800). Six patients did not reach an acceptable visual
      acuity and were not included in the mean BSCVA, 2 had a primary failure, and the
      others had preexisting glaucoma or macular disease. Spherical equivalent was 
      0.04 +/- 1.2 D, refractive astigmatism was 1.76 +/- 1.69 D, surface regularity
      index was 0.97 +/- 0.54, and surface asymmetry index was 1.25 +/- 0.78 1 year
      after surgery. Mean endothelial cell count from the donor was 2904 +/- 559
      (range, 4694-2111) and 1 year after surgery was 1595 +/- 662 (range, 702-3040),
      equating to 45% cell loss (range, 15%-77%). CONCLUSIONS: DLEK is a newer method
      to replace the endothelium in patients with Fuchs dystrophy. Results showed
      minimal astigmatism, good topographic parameters, and acceptable visual acuity.
      Endothelial cell loss at 1 year was significant.

PMID- 17525646
TI  - SmartPlug in the management of severe dry eye syndrome.
AB  - PURPOSE: To evaluate long-term efficacy and safety of the SmartPlug in the
      management of severe dry eye syndrome. METHODS: A retrospective chart review was
      conducted of patients who underwent SmartPlug insertion from June 2003 to
      December 2005. The clinical data collected included sex and age of the patients,
      indications for plug insertion, Schirmer tear function test with anesthesia,
      frequency of lubricant eye drop use before and after plug insertion, fluorescein
      staining at baseline and at last follow-up, and complications. RESULTS: There
      were 91 eyes of 54 patients (44 women and 10 men) in the study group. The average
      follow-up period was 13.0 +/- 6.0 months, with a minimum of 6 months. Thirty
      patients (55 eyes, 60.4%) reported a decreased use of lubricant eye drops after
      SmartPlug insertion, including 9 patients (14 eyes, 15.4%) who were free of
      supplementary lubricant eye drops. Forty-one patients (69 eyes, 75.8%) reported
      subjective symptom improvement after SmartPlug insertion. The corneal fluorescein
      staining showed overall reduction. Complications included canaliculitis (6 eyes,
      6.6%), epiphora requiring plug removal (5 eyes, 5.5%), and spontaneous plug loss
      (2 eyes, 2.2%). CONCLUSIONS: SmartPlug can be effective in the management of
      severe dry eye syndrome. However, long-term follow-up is needed for potentially
      serious complications such as canaliculitis.

PMID- 17525647
TI  - Does blunt ocular trauma induce corneal astigmatism?
AB  - PURPOSE: To determine the effect of blunt ocular trauma on refractive
      astigmatism. METHODS: Eighty-six eyes of 86 patients with known previous
      refractive status exposed to blunt ocular trauma were included in the study.
      Trauma-induced astigmatism (TIA) was calculated using vector analysis. In eyes
      with TIA, central corneal thickness was assessed by ultrasound pachymetry, and
      corneal topographies were obtained. Anterior-chamber angles were examined by
      Goldmann 3-mirror lens to find microhemorrhages, scarring, or recession. Patients
      were followed up between 8 and 12 months (average, 9.2 months). RESULTS: In 18
      eyes (21%), TIA was detected. Six (7%) of these eyes had lenticular astigmatism
      caused by traumatic lens subluxation. In the remaining 12 eyes (14%), corneal
      topography showed regular astigmatic patterns, which were symmetrical in 3 eyes
      and asymmetric in the remaining 9. The etiologic factor was a game marble in 6
      eyes and a stone in the remaining 6. The mean central corneal thickness was
      535.75 microm (range, 498-570 microm) in these 12 eyes. In 9 of these 12 eyes,
      recession or scarring in the anterior-chamber angle was detected at 1 edge of the
      steepest axis. CONCLUSIONS: Blunt trauma can induce astigmatism. Hard and small
      objects are more likely to induce astigmatism.

PMID- 17525648
TI  - Influence of final corneal thickness in visual acuity after deep lamellar
      endothelial keratoplasty.
AB  - PURPOSE: To determine if the final corneal thickness after deep lamellar
      endothelial keratoplasty (DLEK) is correlated in any way with visual performance.
      METHODS: One hundred fifty-five consecutive eyes without macular disease
      underwent DLEK surgery and had pachymetry recorded at 6 months postoperatively.
      The eyes were grouped according to visual acuity, and pachymetry was correlated
      between groups: group 1 (20/20, 20/25, or 20/30), n = 38; group 2 (20/40 or
      20/50), n = 79; group 3 (20/60, 20/70, or 20/80), n = 30; group 4 (20/100 or
      worse), n = 8. RESULTS: The mean pachymetry, SD, and range of pachymetry for each
      group are as follows: group 1, 0.571 +/- 0.080 mm (range, 0.408-0.784 mm); group
      2, 0.598 +/- 0.080 mm (range, 0.437-0.816 mm); group 3, 0.605 +/- 0.099 mm
      (range, 0.454-0.945 mm); group 4, 0.607 +/- 0.120 mm (range, 0.410-0.781 mm).
      There was no significant correlation between vision and corneal thickness (P =
      0.312). There was no statistical difference in pachymetry among all 4 groups (P =
      0.323). The influence of pachymetry in visual acuity is not relevant (r = 0.03).
      CONCLUSIONS: The variance in corneal thickness in DLEK does not seem to influence
      visual results.

PMID- 17525649
TI  - Long-term outcome in ocular intractable surface disease with Seoul-type
      keratoprosthesis.
AB  - PURPOSE: To evaluate the long-term clinical efficacy of the Seoul-type
      keratoprosthesis (S-KPro). METHODS: S-KPros were implanted into 4 unsighted and 5
      sighted eyes in 9 patients: 6 patients were diagnosed with Stevens-Johnson
      syndrome, 2 had chemical burns, and 1 suffered from ocular pemphigoid. The
      preoperative visual acuity ranged from light perception to hand motion. The
      average follow-up period was 62.8 months. We evaluated several clinical factors,
      including visual acuity, visual field, number of additional grafting procedures,
      number of capsulotomy procedures, and the interval between retinal detachment and
      skirt exposure. RESULTS: The S-KPro showed anatomic success for an average of
      62.8 months in 66.7% of the eyes. The average visual acuity preservation time was
      31.6 months. Localized glaucomatous visual field defect was not found in any of
      the sighted patients; however, diffuse visual field constriction was observed
      after long-term follow-up. Average time of skirt exposure and mean number of
      additional grafting procedures were 12.9 months and 2.44, respectively. Retinal
      detachments were developed in all the patients at a mean time interval of 2
      months after S-KPro exchange. CONCLUSIONS: S-KPro achieved visual rehabilitation
      for an average of 31.6 months with long-term anatomic stability in patients with
      severe intractable ocular surface disease.

PMID- 17525650
TI  - Frequency of positive donor rim cultures after penetrating keratoplasty using
      hypothermic and organ-cultured donor corneas.
AB  - PURPOSE: To compare the frequency of positive rim cultures after penetrating
      keratoplasty using corneas preserved by hypothermic and organ culture storage. To
      evaluate the influence of standard procurement techniques on the frequency of
      microbial donor rim contamination. METHODS: Six hundred four donor corneas stored
      at 31 degrees C and 214 at 4 degrees C were studied. Microbiology studies were
      carried out during organ culture storage, and corneas with positive medium
      cultures were discarded. Frequency of postoperative positive rim cultures was
      related to the type of corneal storage and procurement technique used. RESULTS:
      Thirty-nine (6.4%) corneas with positive medium cultures were discarded during
      organ culture. Microbiology reports of 628 donor rims cultures from 671 (94%)
      consecutive transplants were reviewed. Positive rim cultures resulted in 24
      (3.8%) cases. None of the patients developed endophthalmitis. The frequency of
      postoperative positive rim cultures was greater after hypothermic than organ
      culture storage, being 9.8% and 1.3%, respectively (chi(2) = 24.9; P < 0.001).
      With organ culture storage, the frequency of positive rim cultures was 1.3% and
      1.4% after enucleation and in situ corneal excision, respectively (chi(2) = 0.03;
      P = 0.638). After hypothermic storage, positive rim cultures were found in 8% of
      the corneas procured using enucleation and 12% of the corneas excised in situ
      (chi(2) = 0.829; P = 0.254). CONCLUSIONS: Organ culture storage allows one to
      recognize and discard corneas with microbial contamination during storage. This
      method significantly reduces the frequency of postoperative positive rim cultures
      compared with hypothermic storage. Procurement methods do not influence the
      percentage of positive rim cultures.

PMID- 17525651
TI  - Comparing central corneal thickness in a sub-Saharan cohort to African Americans
      and Afro-Caribbeans.
AB  - PURPOSE: To evaluate the central corneal thickness (CCT) of Africans in a
      glaucoma practice in a university teaching hospital in West Nigeria, Africa, and
      compare results with similar studies carried out in African American and Afro
      Caribbean populations. METHODS: CCT was measured by means of ultrasound
      pachymetry (pachymeter used was Micropach 200 P+ Pachymeter; Sonomed) in only
      African participants with either glaucomatous or healthy eyes. After instillation
      of topical anesthetic, 3 measurements of corneal thickness were taken, and the
      average thickness for each was calculated. The relationship between CCT and age
      was studied using correlation analyses and t tests. A total of 70 eyes were
      included for analysis. RESULTS: The mean CCT of all participants was 532.00
      microm. Glaucoma suspects and patients with glaucoma had corneas thinner than
      those of normal participants (527.36 and 536.91 microm, respectively); however,
      the difference was not significant (P = 0.296). Decreasing values of CCT were
      significantly related to older age (P = 0.002). Men had a significantly higher
      CCT than women (P = 0.035). CONCLUSIONS: CCT values in African populations are
      less than those of whites. Decreasing values of CCT are significantly related to
      older age, and men have thicker corneas than women. There is a suggestion that
      CCT is lower in patients with glaucoma than in nonglaucomatous controls; however,
      the difference is not statistically significant. Comparing our results to other
      studies in literature, it seems that average CCT is similar between populations
      living in sub-Saharan Africa and African Americans and Afro-Caribbeans.

PMID- 17525652
TI  - Indications for penetrating keratoplasty in Iran.
AB  - PURPOSE: To determine the indications for penetrating keratoplasty (PK) in Iran.
      METHODS: : All eye bank records of patients who had undergone PK between 1994 and
      2004 at ophthalmic centers throughout the country were reviewed. RESULTS: During
      this 11-year period, a total of 19,668 cases were operated on. The most common
      indication for PK was keratoconus (n = 6787, 34.51%), followed by corneal opacity
      and scar (n = 3674, 18.68%), pseudophakic bullous keratopathy (n = 1808, 9.19%),
      corneal dystrophies (n = 1272, 6.47%), aphakic bullous keratopathy (n = 1198,
      6.09%), and regraft (n = 1038, 5.28%). There was an increasing trend in rates of
      keratoconus and pseudophakic bullous keratopathy and a decreasing trend in
      aphakic bullous keratopathy over this period (P < 0.001). No significant change
      of trend was noted in the corneal opacity and scar, regraft, and corneal
      dystrophy groups. CONCLUSIONS: Keratoconus is the most common indication for PK
      in Iran.

PMID- 17525653
TI  - Importance of nutrition to corneal grafts when used as a carrier of the Boston
      Keratoprosthesis.
AB  - PURPOSE: Necrosis, melt, and perforation have historically been frequent around a
      Keratoprosthesis (KPro), even resulting in extrusion or endophthalmitis.
      Autoimmune diseases such as Stevens-Johnson Syndrome (SJS) and Ocular Cicatricial
      Pemphigoid (OCP) have been notorious in this respect. The purpose of this study
      was to compare the frequency of tissue melt after implantation of two designs of
      the Boston KPro, one allowing much better access of nutrition from the aqueous
      humor to the carrier graft. METHODS: We retrospectively reviewed charts of 157
      eyes implanted since 1990 with a poly (methylmethacrylate) Boston KPro, including
      79 eyes implanted with the model having 8 small (1.3-mm diameter) holes in the
      back plate, and 78 eyes implanted with the older solid back plate. We compared
      the frequency of tissue melts between the two KPro designs, for all implants as
      well as for subgroups based on preoperative diagnosis. RESULTS: In total, 48/157
      eyes (31%) developed some degree of tissue melt around the stem, including 8/79
      eyes (10%) in the back plate with holes group and 40/78 eyes (51%) in the solid
      back plate group (P < 0.0001). Among the melts in the back plate with holes
      group, 4/8 (50%) suffered from an underlying autoimmune disease such as SJS or
      OCP. CONCLUSIONS: The Boston KPro design with a back plate containing holes
      protects the overlying corneal tissue from necrosis and melts. This improved
      situation is likely due to increased aqueous access and better nutrition to the
      corneal graft cells. In addition, this study confirms earlier work regarding the
      particular corneal fragility of patients with autoimmune diseases.

PMID- 17525654
TI  - Comparison of EphA receptor tyrosine kinases and ephrinA ligand expression to
      EphB-ephrinB in vascularized corneas.
AB  - PURPOSE: Eph cell surface receptors and their ligands, ephrins, are involved in
      neuronal patterning and neovascularization. Our purpose is to compare and
      characterize the expression of ephrinA ligands and EphA receptors to ephrinB
      ligands and EphB receptors in excised mouse corneal tissue, in corneal epithelial
      and keratocyte cell lines, and during corneal angiogenesis. METHODS: Mouse
      corneal epithelial cells and keratocytes were immortalized using SV40T antigen
      viral infection of primary cultures. The immortalized epithelial cells and
      keratocytes were cloned and characterized using antibodies to keratin, vimentin,
      integrin alpha5beta1, and alpha-smooth muscle actin. Basic fibroblast growth
      factor pellets were implanted to induce corneal neovascularization. The eyes of
      wild-type, ephrinB2(tlacZ/+), and EphB4(tlacZ/+) heterozygous mice were harvested
      and sectioned 7 days after pellet implantation. Confocal immunohistochemistry was
      performed to compare the expression of the Eph/ephrinA family (EphA1-8, ephrinA1
      5) and Eph/ephrinB family (EphB1-4, EphB6 ephrinB1-3). RESULTS: EphA1, EphA3,
      ephrinA1, ephrinA2, EphB1, EphB4, ephrinB1, and ephrinB2 were detected in wild
      type mouse corneal epithelial cells and keratocytes. EphA2 was immunolocalized
      only in epithelial cells. Also, EphA3, ephrinA1, EphB1, EphB4, and ephrinB1 were
      immunolocalized to the corneal epithelium and stroma. In the vascularized
      corneas, ephrinB1 was immunolocalized mainly to the keratocytes around the
      vessels, and ephrinB2, EphB1, and EphB4 were colocalized mainly with CD31 to the
      vascular endothelial cells. CONCLUSIONS: The characterization of ephrin ligand
      and Eph receptor expression during cornea angiogensis in this study suggests that
      the Eph/ephrin family of receptor tyrosine kinases and their ligands may play a
      role in the regulation of corneal angiogenesis.

PMID- 17525655
TI  - Strain-related cytokine profiles on the murine ocular surface in response to
      desiccating stress.
AB  - PURPOSE: To evaluate the effects of desiccating ocular surface stress on levels
      of inflammatory cytokines in the corneal epithelium, conjunctiva, and tear fluid
      of BALB/c and C57BL/6 mice. METHODS: Experimental dry eye (EDE) was created in
      BALB/c and C57BL/6 mice by cholinergic blockade and exposure to a desiccating
      environment. Real-time polymerase chain reaction was performed to measure levels
      of cytokine transcripts. A multiplex immunobead assay was used to measure
      concentrations of these cytokines in tears. RESULTS: Experimental dryness
      significantly increased the expression of interleukin (IL)-1alpha, IL-6, and
      tumor necrosis factor (TNF)-alpha transcripts in the corneal epithelium and
      conjunctiva of C57BL/6 mice. Strain-specific changes in tear cytokine profiles
      were observed. C57BL/6 mice had significantly greater tear concentrations of IL
      1alpha and TNF-alpha and the Th-1 cytokines IL-2, IL-12, and interferon-gamma in
      response to desiccating stress than BALB/c mice. The Th-2 cytokines IL-4 and IL
      10 were significantly greater in BALB/c tears. CONCLUSIONS: This study indicates
      that desiccating stress increases levels of certain cytokines in the corneal
      epithelium and conjunctiva in a strain-dependent fashion and that C57BL/6 mice
      had greater levels of Th-1 cytokines in their tears, whereas BALB/c mice had a
      greater increase in Th-2 cytokines.

PMID- 17525656
TI  - Zymar (Gatifloxacin 0.3%) shows excellent Gram-negative activity against Serratia
      marcescens and Pseudomonas aeruginosa in a New Zealand White rabbit keratitis
      model.
AB  - PURPOSE: Whereas gatifloxacin, a newer fluoroquinolone, was engineered to
      increase its Gram-positive potency, we assessed whether it still retained
      significant Gram-negative activity in vivo. Specifically, we compared the
      efficacy of Zymar (gatifloxacin 0.3%), Ciloxan (ciprofloxacin 0.3%), and
      fortified tobramycin (14 mg/mL) in the treatment of experimental Gram-negative
      bacterial infections of Serratia marcescens (SM) and Pseudomonas aeruginosa (PA)
      in the New Zealand White (NZW) rabbit keratitis model. METHODS: A total of 30 NZW
      rabbits each were intrastromally inoculated in both eyes with approximately 1000
      CFU of SM and PA. By E-test, the minimum inhibitory concentrations (MICs;
      microg/mL) for SM were gatifloxacin (0.125), ciprofloxacin (0.047), and
      tobramycin (1.5), and for PA were gatifloxacin (0.125), ciprofloxacin (0.19), and
      tobramycin (0.5). After 16 hours, the rabbits were divided into 4 treatment
      groups: (1) Zymar, (2) Ciloxan, (3) fortified tobramycin, and (4) saline control.
      One drop was instilled in both eyes every 15 minutes for 5 doses and then every
      30 minutes for 14 doses. One hour after the final treatment, the animals were
      euthanized, and bacterial colony counts from the corneas were determined.
      RESULTS: For SM, Zymar and Ciloxan significantly reduced (P < 0.001, ANOVA) the
      colony counts compared with tobramycin and saline control. Zymar was more
      effective than Ciloxan (P < 0.001, ANOVA). For PA, all antibiotics reduced
      equivalently the colony counts compared with the saline control (P = 0.005,
      ANOVA). CONCLUSIONS: The enhanced Gram-positive activity of gatifloxacin is not
      associated with any decreased Gram-negative activity in vivo. Zymar may prove
      useful for SM and PA keratitis.

PMID- 17525657
TI  - Expression of matrix metalloproteinases 2 and 9 in experimental corneal injury
      and fungal keratitis.
AB  - PURPOSE: Levels of matrix metalloproteinases (MMPs) can be modulated during
      corneal infection, but little is known about MMP profiles during fungal
      keratitis. The purpose of this study was to determine the effect of corneal
      trauma and immunosuppressive treatment on the expression kinetics of MMP-2 and
      MMP-9 during experimental keratomycosis. METHODS: Corneas of immunocompetent and
      cyclophosphamide-treated adult BALB/c mice were topically inoculated with 1 x 10
      culturable units of Fusarium solani or mock-inoculated with or without
      superficial corneal scarification. Eyes were scored daily for disease severity
      and processed for zymography after 1.5 hours, 6 hours, 1 day, 4 days, or 8 days.
      Gelatinase activity was densitometrically quantitated and normalized to MMP-2 and
      MMP-9 controls. RESULTS: MMP-9 levels in nontraumatized eyes transiently
      increased at 6 hours after fungal exposure, but this increase was inhibited by
      cyclophosphamide treatment. Corneal injury significantly induced early MMP-9
      expression that returned to baseline levels within 4 days. Cyclophosphamide
      pretreatment reduced and delayed MMP-9 after scarification. Fusarium exposure
      dampened the MMP-9 response to corneal trauma in immunocompetent and
      cyclophosphamide-treated animals. Ocular levels of MMP-2 were not affected by
      scarification, fungal exposure, or immunosuppressive treatment. CONCLUSIONS:
      Ocular MMP-9 levels, but not MMP-2 levels, increased soon after corneal injury. A
      similar, although muted, MMP-9 response occurs during early filamentous fungal
      keratitis, with a kinetic profile similar to corneal disease progression. The
      early stage of ulcerative keratitis may involve selective regulation of corneal
      matrix metalloproteinases, suggesting an initial opportunity for therapeutic
      intervention.

PMID- 17525658
TI  - Screening for previous refractive surgery in eye bank corneas by using optical
      coherence tomography.
AB  - PURPOSE: To use optical coherence tomography (OCT) to detect previous refractive
      surgery in donor corneas. METHODS: We constructed a tabletop OCT scanner
      operating at 1310-nm wavelength. Donor corneas at the Cleveland Eye Bank were
      scanned while sealed within the sterile container immersed in Optisol GS. OCT
      scanning was performed with 7.6-mm-long lines (512 axial scans) along 8
      meridians. Anterior and posterior corneal surfaces were automatically mapped
      using image processing software that we developed. Curvature was computed from
      the best parabolic fit in the central 5-mm diameter. Layered analysis of the
      stromal reflectivity was also performed. Twenty-nine corneas from 19 donors were
      examined. Five had a history of laser in situ keratomileusis (LASIK). RESULTS:
      The flap interfaces could not be visualized on slit-lamp or OCT images but were
      confirmed by histology. The death-to-scan time was 22.1 +/- 11.4 (SD) hours for
      normal corneas and 100.6 +/- 57.5 hours for LASIK corneas. The anterior surface
      power was 67.5 +/- 2.5 D in control corneas and 64.5 +/- 2.4 D in LASIK corneas
      (P = 0.023). There was no significance between the 2 groups in terms of posterior
      curvature and thickness parameters. The anterior/posterior reflectivity ratio in
      the central 4-mm diameter was significantly lower in post-LASIK corneas than in
      control (P < 0.05). CONCLUSIONS: OCT provides thickness, topography, and
      reflectivity maps of donor corneas without taking them out of preservation medium
      and container. The anterior curvature and the anterior/posterior stromal
      reflectivity ratio may be useful for detecting previous LASIK.

PMID- 17525659
TI  - Wound healing in the rabbit cornea after corneal collagen cross-linking with
      riboflavin and UVA.
AB  - PURPOSE: This study was undertaken to investigate the wound healing process of
      the first 6 weeks after photodynamic cross-linking treatment in the rabbit
      cornea, using the photosensitizer riboflavin and UVA. METHODS: After removal of
      the central epithelium, the right corneas of 8 Chinchilla rabbits were cross
      linked with a photosensitizing 0.1% riboflavin solution and UVA light (370 nm;
      irradiance, 3 mW/cm(2); dose, 5.4 J/cm(2)) for 30 minutes. Two animals were
      euthanized 3 days, 7 days, 4 weeks, and 6 weeks postoperatively. The corneas of
      the enucleated eyes were evaluated using 4-microm light microscopic sections with
      routine stains and avidin-biotin complex immunostaining with anti-alpha-smooth
      muscle actin. RESULTS: By day 3 after treatment, complete apoptotic damage and
      loss of the endothelial cells and the stromal keratocytes were found in the
      irradiated area through the entire thickness of the stroma. There was marked
      stromal edema (850 +/- 66 vs. 332 +/- 43 microm in the untreated controls; P <
      0.01). The epithelium was already closed again. At the margins of the lesion,
      there was a mild inflammatory reaction with scattered macrophages, lymphocytes,
      and neutrophils. By day 7, the endothelium was already intact again, and
      keratocyte repopulation of the posterior stroma was noted. By week 4, the
      keratocyte repopulation of the anterior stroma was observed with some acellular
      areas between. By week 6, the cytoarchitecture of the cornea seemed normal again.
      By weeks 4 and 6, alpha-actin-positive keratocytes were identified, especially in
      the periphery of the irradiated area. CONCLUSIONS: After riboflavin/UVA cross
      linking of rabbit cornea, a complete cell loss occurs in the irradiation area
      with an irradiance of 3 mW/cm(2). The cytotoxic damage is repaired by
      repopulation after approximately 4-6 weeks. A combination of cross-linking with
      other procedures such as the implantation of intracorneal rings should be
      performed only after a sufficient time interval of approximately 2 months,
      allowing cellular regeneration.

PMID- 17525660
TI  - Effect of fourth-generation fluoroquinolones on the healing rate of corneal
      erosions in an animal model.
AB  - PURPOSE: To compare the rate of epithelial healing of corneal erosion in an
      animal model with 2 commercial formulations of fourth-generation
      fluoroquinolones: 0.3% gatifloxacin and 0.5% moxifloxacin. METHODS: Corneal
      erosions, 6 mm in diameter, were created in 28 rabbit eyes. The rabbits were
      randomized to receive topical gatifloxacin, moxifloxacin, or nonpreserved saline.
      Drops were administered every 15 minutes for 1 hour, then hourly for 3 hours, and
      then 4 times daily until the erosion reepithelialized. Eyes were examined with
      fluorescein drops and photographed every 12 hours with a cobalt blue-filtered
      light. When reepithelialization was observed, the rabbits were euthanized, and
      their eyes were enucleated for histopathologic evaluation. RESULTS:
      Reepithelialization of the corneal erosions was fastest in the saline-treated
      eyes (57.3 +/- 8 hours), followed by moxifloxacin (62.7 +/- 11.7 hours) and
      gatifloxacin (66 +/- 8.5 hours). These differences in the time to closure of the
      erosions among the 3 groups were not statistically significant. Although
      significant differences were found among the healing progression curves when all
      3 groups were compared (P = 0.042), the difference between the 2 antibiotic
      treated groups was not significant. CONCLUSIONS: Only slight differences in
      epithelial healing rates were found between the gatifloxacin-, moxifloxacin-, and
      saline-treated groups, suggesting that the 2 fluoroquinolones may have an
      equivalent role as prophylactic treatment of trauma- or surgery-induced corneal
      erosions.

PMID- 17525661
TI  - Morphologic and volumetric studies of the meibomian glands in elderly human
      eyelids.
AB  - PURPOSE: To study the microscopic structure of postmortem human Meibomian glands
      (MGs) in the elderly. METHODS: Human MG samples from left lower eyelids were
      obtained at autopsy from 5 men and 4 women with a mean age of 63.1 +/- 7.67
      years. The tissues were fixed and embedded in paraffin. Serial transverse
      sections 5 mum thick were stained with hematoxylin and eosin (H&E), van Gieson,
      and Masson blue stains. Computer-assisted 3-dimensional reconstructions of MGs
      were performed, and morphologic and volumetric data were analyzed. RESULTS: The
      average length of human MGs in the nasal, central, and temporal areas was 1.551
      +/- 0.43, 1.654 +/- 0.47, and 1.594 +/- 0.57 mm, respectively. The average
      surface area of the glands in the nasal, central, and temporal areas was 0.029 +/
      0.03, 0.033 +/- 0.01, and 0.056 +/- 0.03 mm, respectively. The average volume of
      glands in the nasal, central, and temporal areas was 0.054 +/- 00.4, 0.056 +/-
      0.03, and 0.053 +/- 0.03 mm, respectively. A circular, floral arrangement of
      acini, surrounding the terminal duct just deep to the skin, is probably
      responsible for the circular arrangement seen clinically around each healthy
      orifice. We confirmed that most glands are embedded within a cylindrical,
      connective tissue matrix. CONCLUSIONS: We report the dimensions of normal
      Meibomian acini in an older population. Some structural features observed may
      explain normal physiologic landmarks or contribute to glandular pathophysiology.

PMID- 17525662
TI  - Herpes simplex keratitis after cataract surgery.
AB  - PURPOSE: Herpetic keratitis is a rare complication of cataract surgery. We
      describe 3 cases of herpes simplex keratitis after cataract surgery in eyes with
      no clinical history of this disease. METHODS: Three patients underwent uneventful
      phacoemulsification of cataract with intraocular lens implantation. All were
      treated postoperatively with topical steroids. On subsequent development of
      corneal dendritic epithelial lesions in the operated eyes, the corticosteroids
      were replaced by treatment with topical acyclovir. RESULTS: The first
      postoperative day was uneventful. Corneal dendritic epithelial lesions were
      observed 1-5 weeks postoperatively and healed without sequelae after topical
      acyclovir treatment. CONCLUSIONS: In view of the surgical trauma along with the
      topical corticosteroid treatment commonly prescribed after cataract surgery,
      physicians should be aware of the possible development of herpetic epithelial
      keratitis even in patients with no clinical history of this disease.

PMID- 17525663
TI  - Diagnostic and therapeutic challenge of Aspergillus flavus scleritis.
AB  - PURPOSE: To discuss the diagnostic and therapeutic challenges involved in the
      management of Aspergillus flavus scleritis and present a review of related
      literature. METHODS: Case report and literature review. RESULTS: A healthy 54
      year-old woman presented with a 1-week history of severe pain and redness in her
      left eye. She was treated with prednisone for presumed idiopathic autoimmune
      scleritis after extensive evaluation revealed no apparent etiology. While on
      immunosuppressant therapy, the patient developed a scleral nodule that proved to
      be a scleral abscess with normal overlying scleral architecture. Culture of the
      abscess and extensive infectious disease evaluation did not offer an etiologic
      explanation. Biopsy of a subsequent scleral nodule revealed fungal hyphae on
      fixed tissue stains, and A. flavus was identified on fungal culture. The patient
      later acknowledged intravenous drug use in the 2 months preceding her
      presentation. Oral voriconazole and intravenous caspofungin along with repeated
      surgical drainage of emerging scleral abscesses eradicated the active disease
      after 3 months. CONCLUSIONS: Despite its rare occurrence, Aspergillus sp. should
      be considered as a potential cause of an unusual progressive scleritis. Specific
      questioning regarding intravenous drug use may prove relevant. Scleral biopsy was
      instrumental in establishing the diagnosis. Aggressive multidrug medical therapy
      combined with repeated surgical debridement resulted in a positive clinical
      outcome.

PMID- 17525664
TI  - Clinical response of contact lens-associated fungal keratitis to topical
      fluoroquinolone therapy.
AB  - PURPOSE: To report 5 cases of fungal keratitis associated with contact lens wear
      that resolved or significantly improved without antifungal therapy. METHODS:
      Observational case report of 5 patients with a history of contact lens wear who
      presented with infectious keratitis. Two patients had growth of fungal species on
      corneal microbiologic cultures, and of the remaining 3 patients, 2 showed fungal
      elements on confocal microscopy. All 5 patients exhibited growth of fungal
      species on contact lens microbiologic cultures. All patients received topical
      fluoroquinolone therapy as initial treatment. RESULTS: In 3 cases, of whom 2 were
      treated with moxifloxacin 0.5%, the keratomycosis resolved completely on topical
      fluoroquinolone therapy. One case was switched to topical tobramycin 14 mg/mL and
      cefazolin 50 mg/mL with complete resolution of the infection. The final case
      showed marked initial improvement on fluoroquinolone therapy but was subsequently
      treated with natamycin 5%. CONCLUSIONS: Fungal keratitis associated with soft
      contact lens wear may occasionally present in a less aggressive form. Topical
      fluoroquinolone therapy may be an adjunct to the innate immune response in
      eradicating less fulminant keratomycosis.

PMID- 17525665
TI  - Corneal perforation associated with pellucid marginal degeneration and treatment
      with crescentic lamellar keratoplasty: two case reports.
AB  - PURPOSE: To describe 2 cases of corneal perforation associated with pellucid
      marginal degeneration (PMD) and subsequent successful management with crescentic
      lamellar keratoplasty. METHODS: Two cases are discussed along with the relevant
      literature. RESULTS: Both patients presented with spontaneous corneal
      perforations and associated features consistent with PMD. In both cases, there
      was fellow eye evidence of PMD, and 1 of the patients was already known to our
      unit with this diagnosis. Initial conservative measures were unsuccessful, and
      both patients underwent crescentic lamellar keratoplasty as the definitive
      surgical management with a good visual outcome. CONCLUSIONS: Crescentic lamellar
      keratoplasty is an effective technique for the management of this rare
      complication of PMD.

PMID- 17525666
TI  - Use of amniotic membrane graft and corneal transplantation in a patient with
      bilateral keratomalacia induced by uncontrolled phenylketonuria.
AB  - PURPOSE: To report a patient with a rare complication of bilateral keratomalacia
      induced by uncontrolled phenylketonuria (PKU) that was successfully treated with
      amniotic membrane transplantation in 1 eye and penetrating keratoplasty in the
      second eye. METHODS: Case report and literature review. RESULTS: A 9-month-old
      girl with uncontrolled PKU was referred to our clinic because of bilateral
      keratomalacia. Slit-lamp examination of the right eye revealed 2 large corneal
      erosions with stromal thinning on the nasal and inferior regions of the right
      cornea. Left eye examination revealed a large area of melting involving two
      thirds of the cornea with corneal perforation and iris bulging on the temporal
      side and no anterior chamber. She underwent amniotic membrane transplantation on
      her right cornea and penetrating keratoplasty on her left cornea. Treatment after
      surgery included antibiotic and steroid eye drops and a special diet regimen with
      partial phenylalanine intake. Examination under anesthesia 4 months after surgery
      revealed intact cornea in her right eye and a clear corneal graft with a deep
      anterior chamber on her left eye. Intraocular pressure was normal in both eyes.
      CONCLUSIONS: Bilateral keratomalacia, although a rare ophthalmic manifestation of
      PKU, can cause a severe corneal injury that may threaten the eyeball integrity.
      Surgical treatments with amniotic membrane graft and corneal transplantation,
      along with the appropriate diet treatment, were found to be effective procedures,
      yielding rapid healing of the corneal surface.

PMID- 17525667
TI  - Resolution of autoimmune polyglandular syndrome-associated keratopathy with
      keratolimbal stem cell transplantation: case report and historical literature
      review.
AB  - PURPOSE: To describe the presentation and treatment of a case of autoimmune
      polyglandular syndrome type 1 (APS1)-associated keratopathy and to review the
      associated literature. METHODS: A 23-year-old man with decreased vision secondary
      to APS1-associated keratopathy was treated with systemic immunosuppression and
      keratolimbal allograft (KLAL) stem cell transplantation. RESULTS: The patient
      maintains excellent vision 27 months after KLAL and systemic immunosuppression.
      CONCLUSIONS: An underlying etiology of APS1-associated keratopathy is stem cell
      deficiency, which can be treated effectively with KLAL and systemic
      immunosuppression.

PMID- 17525668
TI  - Intracameral C(3)F(8) injection for descemet membrane detachment after
      phacoemulsification in deep anterior lamellar keratoplasty.
AB  - PURPOSE: To report a case of Descemet membrane detachment (DMD) after cataract
      surgery in an operated case of deep anterior lamellar keratoplasty (DALK).
      METHODS: Phacoemulsification surgery with intraocular lens implantation was
      performed in the left eye of a 65-year-old woman who had previously undergone
      DALK. DMD was noted intraoperatively, for which intracameral injection of air was
      done at the end of surgery. On the first postoperative day, DMD was seen, and
      hence, intracameral 20% sulfur hexafluoride (SF(6)) gas was injected. Because the
      DMD did not resolve, intracameral 14% C(3)F(8) gas was injected on the seventh
      postoperative day. RESULTS: At the 3-week follow-up, complete resolution of DMD
      was seen. CONCLUSIONS: DMD that occurs during phacoemulsification in a case that
      has previously undergone DALK can be effectively and safely resolved using
      intracameral C(3)F(8) gas injection.

PMID- 17525669
TI  - Late corneal hydrops after penetrating keratoplasty for keratoconus.
AB  - PURPOSE: To report 2 cases of corneal hydrops occurring in eyes with previously
      healthy corneal grafts. METHODS: Retrospective case series. A report of 2
      presenting cases. Both patients underwent a full ophthalmic clinical examination
      and anterior segment optical coherence tomography (OCT). RESULTS: Two patients
      with longstanding corneal grafts for keratoconus presented with an acute painful
      red eye and reduced vision. They were found to have acute hydrops with breaks in
      and detachments of Descemet membrane. CONCLUSIONS: Keratoconic patients with
      longstanding corneal grafts who present acutely with corneal edema must be
      carefully examined not only for signs of graft rejection or failure but also for
      acute hydrops. Important differentiating signs may be a Descemet break or
      detachment and the presence of stromal edema across the donor-host corneal
      interface.

PMID- 17525670
TI  - Herpes simplex keratitis after intravitreal triamcinolone acetonide.
AB  - PURPOSE: To report a case of recurrent herpes simplex virus (HSV) epithelial
      keratitis after intravitreal triamcinolone acetonide injection for the treatment
      of diabetic macular edema. METHODS: Case report. RESULTS: We describe a case of a
      59-year-old woman with a history of ocular HSV disease and severe proliferative
      diabetic retinopathy. She received an intravitreal injection of triamcinolone
      acetonide for macular edema in the right eye. One week later, she developed
      foreign body sensation, redness, and photophobia in the same eye. Slit-lamp
      examination revealed a corneal epithelial dendritic lesion. She was diagnosed
      with a recurrence of HSV epithelial keratitis and was treated with oral acyclovir
      400 mg, 5 times a day, with good resolution of HSV signs and symptoms.
      CONCLUSIONS: Intravitreal triamcinolone acetonide injection may result in
      reactivation of HSV keratitis.

PMID- 17525671
TI  - Infectious crystalline keratopathy caused by Gemella haemolysans.
AB  - PURPOSE: To report a novel case of infectious crystalline keratopathy after
      penetrating keratoplasty caused by Gemella haemolysans. METHODS: Observational
      case report. Patient notes and literature review. RESULTS: A 51-year-old woman
      presented with the clinical picture of infectious crystalline keratopathy 18
      months after a second penetrating keratoplasty was performed for corneal
      decompensation secondary to recurrent herpes simplex infection. Corneal biopsy
      yielded a heavy growth of G. haemolysans. Initial treatment was made up of
      frequent topical vancomycin 0.5% and was later changed to topical cefuroxime 5%
      and ofloxacin 0.3%. Snellen visual acuity after complete resolution of the
      keratitis was 6/60 as a result of a residual corneal scar. CONCLUSIONS: Gemella
      haemolysans may be an etiologic agent in infectious crystalline keratopathy. A
      corneal biopsy may be diagnostic but may also promote healing by allowing direct
      access of antibiotics to deep-seated infected tissue and by altering the growth
      environment of the organism.

PMID- 17525672
TI  - Welding without the use of eye protective equipment.

PMID- 17525674
TI  - Optimization of RNA extraction from formalin-fixed, paraffin-embedded lymphoid
      tissues.
AB  - Comprehensive analysis of gene expression using RNA extracted from frozen
      lymphoma specimens is becoming increasingly important for understanding disease
      pathogenesis, disease subclassification, and prognostication. As paraffin tissues
      are widely available whereas frozen specimens are not, development of gene
      expression analysis based on RNA extracted from paraffin-embedded tissues would
      facilitate application of the accumulated knowledge to a sample type that is
      typical of clinical practice. In the present study, we have developed and
      optimized methods of RNA extraction from paraffin-embedded lymphoid tissues. In
      contrast to previously suggested methods of RNA extraction from paraffin, our
      method uses sodium dodecyl sulfate that better preserves the extracted RNA and is
      optimized for more complete proteinase K digestion to release RNA from its
      complexes with protein. These modifications yield long RNA fragments up to 2000
      bp enabling amplification of long amplicons. This allows usage of paraffin
      specimens for molecular rescue of RNA transcripted from rearranged clonal
      immunoglobulin genes-an advance that may increase the eligibility of lymphoma
      patients for immunotherapeutic approaches. Furthermore, real-time polymerase
      chain reaction analysis of expression of genes implicated in determination of
      prognosis of diffuse large B-cell lymphoma patients demonstrated an extremely
      high correlation (R>0.90) in normalized gene expression between paired frozen and
      formalin-fixed, paraffin-embedded specimens. Similarly, good correlation was also
      observed in gene array studies. These results suggest that the methods of RNA
      extraction we propose are suitable for giving accurate real-time quantitative
      reverse transcriptase-polymerase chain reaction results, array gene expression
      profiling, and molecular rescue of RNA transcripted from rearranged
      immunoglobulin genes for diagnostic and immunotherapeutic approaches.

PMID- 17525675
TI  - Analytic validation of a quantitative real-time PCR assay to measure CMV viral
      load in whole blood.
AB  - Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in
      immunocompromised patients. We compared the CMV pp65 antigenemia test with a less
      labor intensive quantitative polymerase chain reaction (PCR) assay in 109 whole
      blood samples predominantly from transplant patients and patients with AIDS. DNA
      was amplified on an Applied Biosystems 7900 instrument using a TaqMan probe
      targeting the CMV polymerase gene and the APOB human control gene. The DNA assay
      was linear over a 6-log range from 8 to 800,000 CMV genomes per reaction;
      coefficient of variation was 20%. CMV DNA was undetectable in 20 blood samples
      from healthy donors whereas it was detected in 55 of 109 patient samples. Results
      were concordant in a nonlinear fashion with those of the antigenemia test in
      90/109 (83%). Evaluation of the discrepancies suggested that either PCR or
      antigenemia assays could be falsely negative when virus levels were quite low. A
      point mutation interfered with probe binding in 1 sample. A second real-time PCR
      targeting the immediate early gene was even more likely to be false negative. In
      summary, CMV viral load measurement targeting the polymerase gene is nearly
      equivalent to the antigenemia assay for detecting and monitoring active CMV
      infection in whole blood samples.

PMID- 17525676
TI  - Application of real-time PCR to recognize atypical mycobacteria in archival skin
      biopsies: high prevalence of Mycobacterium haemophilum.
AB  - Atypical mycobacterial skin infections are difficult to diagnose owing to their
      aspecific histopathologic presentations and to the presence of few bacteria.
      Therefore, these infections are often not recognized. Molecular detection of
      mycobacterial DNA has proven to be useful in clinical samples. The aim of this
      study was to investigate the incidence of mycobacterial involvement in skin
      biopsies showing granulomatous inflammation, using real-time polymerase chain
      reaction (PCR). Real-time PCR specific for the genus Mycobacterium and the
      species Mycobacterium avium and Mycobacterium haemophilum was performed on
      formalin-fixed/paraffin-embedded biopsies from patients with granulomatous
      inflammation of the skin, from the period 1984 to 2004. A control group was
      assembled from patients with proven basal cell carcinoma. Amplicons of all
      positive reactions were sequenced to confirm or identify the mycobacterial
      species. Of 30 patients, 13 (43%) were found to be positive for mycobacterial
      infection, of whom only 5 patients had been previously diagnosed with a
      mycobacterial disease. M. haemophilum was identified as the most common species
      (n=7). The other identified species were Mycobacterium malmoense, Mycobacterium
      gordonae, and Mycobacterium marinum. The results show that real-time PCR is
      useful in detecting mycobacterial infections in undiagnosed formalin
      fixed/paraffin-embedded skin samples and that the application of molecular
      approaches would improve the diagnoses of mycobacterial skin infections.

PMID- 17525677
TI  - Molecular alterations in atypical adenomatous hyperplasia occurring in benign and
      cancer-bearing lungs.
AB  - Atypical adenomatous hyperplasia (AAH) is considered to be a precursor lesion of
      the lung adenocarcinoma. Several genetic abnormalities have been reported in AAH
      associated with adenocarcinoma, but little is known about AAH associated with
      benign lung lesions. To address this we compared the molecular characteristics of
      AAH present in benign conditions to those coexisting with carcinoma. Seven cases
      of AAH from resected non-neoplastic lungs (AAH-B) and 12 cases from lungs
      resected for primary lung carcinoma (AAH-M) were analyzed for loss of
      heterozygosity (LOH) using 21 polymorphic microsatellite markers situated in
      proximity to known tumor suppressor genes on chromosomes 3p, 5q, 7p, 9p, 10q, and
      17p. Direct DNA sequencing for K-ras mutation was also performed. There was a
      broad range of LOH in both groups. No LOH was identified in 3 cases (25%) of AAH
      M, but all cases of AAH-B showed LOH (P=0.26). Six cases (50%) of AAH-M and 3
      cases (43%) of AAH-B showed loss at 1 marker (P=0.99). LOH at 2 or more markers
      was identified in 3 (25%) cases of AAH-M and 4 (57%) cases of AAH-B (P=0.32). LOH
      was most frequently detected on chromosomes 3p and 10q in both groups. The
      difference in overall fractional allelic loss between the 2 groups did not reach
      statistical significance. K-ras mutations were not identified in either group.
      Our results showed a significant overlap in LOH patterns between AAH with or
      without coexistent lung malignancy. Therefore, AAH may represent a smoking
      induced low-grade neoplastic lesion that may be a precursor lesion of only a
      subset of invasive lung adenocarcinoma.

PMID- 17525678
TI  - Limitations in molecular detection of lymph node micrometastasis from colorectal
      cancer.
AB  - Colorectal cancer patients with lymph node metastasis have a shorter survival and
      may require adjuvant therapy after surgery of the primary tumor. It is supposed
      that a more reliable diagnosis can be achieved using tumor-specific DNA mutations
      for the detection of metastasizing cells. To design a practical approach for a
      molecular diagnosis of micrometastasis, we applied direct DNA sequencing to
      screen 48 early stage colorectal carcinomas for the most frequent mutations of
      the KRAS, P53, and APC tumor genes. KRAS mutations were detected as frequently as
      described earlier. In contrast, the frequency of P53 and APC hot spot mutations
      was unexpectedly low, compared with previous studies using other screening
      methods or including advanced tumor stages. Not more than 31% of early stage
      tumors showed a mutation in at least 1 of the selected hot spot codons. Applying
      mutant-enriched polymerase chain reaction (PCR), the mutation of the primary
      tumor was detected in lymph node DNA from 2 of the KRAS-positive patients. In 1
      patient, the result was not verified by subtractive iterative PCR, a principally
      different molecular method with high sensitivity and specificity. Our data
      suggest that screening for suitable markers for a molecular detection of occult
      lymph node metastasis cannot be restricted to small-sized hot spot regions of a
      few tumor genes and possibly must include tumor-specific epigenetic changes.
      Furthermore, restriction enzyme-based methods such as mutant-enriched PCR are not
      suitable to detect any mutation with equal efficiency and they should be
      carefully controlled to avoid false-positive detection of marker mutations in
      lymph node DNA.

PMID- 17525679
TI  - Chromosomal alteration in Chinese sporadic colorectal carcinomas detected by
      comparative genomic hybridization.
AB  - Much information has been reported on the genetic and genomic alterations in
      colorectal cancer (CRC) in literature; however, nonrandom chromosomal alterations
      in Chinese CRC patients have only one report in Hong Kong. To further identify
      genomic alteration in primary sporadic colorectal carcinomas (SCRC) in Chinese
      patients and understand the molecular mechanisms in CRC development, progress,
      and metastasis, we used comparative genomic hybridization to screen for losses
      and/or gains of DNA copies along chromosomes in 24 SCRC tissues from 24 patients.
      Comparative genomic hybridization was applied to investigate the genomic
      imbalance in 24 cases of primary SCRC and compared the differences between tumors
      in different loci and between tumors with and without metastasis. The common
      chromosomal alterations in the SCRC included gains of chromosomes 1q, 2q, 4q, 7q,
      8q, 11q, 13q, 20q and also losses of chromosomes 9p, 16q, 17p, 18q. Among them,
      gains of 1q, 7q, 20q and losses of 17p, 18q were related with lymph node
      metastasis of SCRC (P<0.05). The gains of 4q, 7q, 20q and losses of 9p, 18q were
      related with the sites (P<0.05), colon and rectum, respectively; gain of 20q and
      loss of 9p were commonly found in the colon cancer; gain of 4q, 7q and loss of
      18q were easily seen in the rectal cancer. There are multiple regions of
      chromosomes with copy-number changes in SCRC. The tumor suppressor genes and
      oncogenes on these regions may be involved in the development and progress of
      SCRC. The chromosome 1q, 2q, 4q, 7q, 8q, 11q, 13q, 20q regions may have oncogenes
      such as epidermal growth factor, MET, platelet-derived growth factor receptor A,
      and 9p, 16q, 17p, 18q regions may have tumor suppressor genes such as p53,DCC,
      IGFR1 associated with occurrence of SCRC. The chromosome 1q, 7q, 20q, 17p, 18q
      regions may have genes related with metastasis of SCRC. The development
      mechanisms of colon cancer and rectal cancer may not be completely similar.
      Additionally, gain of chromosome 1q was verified by the second technique-Real
      time reverse transcription PCR.

PMID- 17525680
TI  - Epigenetic inactivation of the hMLH1 gene in progression of gliomas.
AB  - Gliomas (GLs) are characterized by highly variable biologic behavior. After
      surgical resection and postoperative therapy, they frequently recur with the same
      or higher-grade histology. Although a number of genetic aberrations have been
      described in different histologic types of GLs, the molecular mechanisms of
      histologic and clinical progression are poorly understood. In this study, we have
      performed longitudinal mismatch repair gene polymerase chain reaction-single
      strand conformation polymorphism and methylation analysis in paired samples of
      primary and recurrent GLs to reveal whether the inactivation of the normal DNA
      repair mechanism is associated with tumor progression. Polymerase chain reaction
      single strand conformation polymorphism analysis of the hMLH1 gene was performed
      in 24 cases, in each case the samples of the first and second biopsies being
      evaluated simultaneously, but no alterations in the hMLH1 gene were found.
      Methylation analysis of the CpG sites in the hMLH1 promoter revealed a total of 4
      (16.6%) hypermethylations in recurrent GLs. These results suggest that hMLH1
      promoter hypermethylation may occur in low-grade GLs, associated with the
      development and progression of moderate malignant GL, but not with structural
      alterations in the hMLH1 gene. It seems that hMLH1 promoter hypermethylation is
      an early event in the development and progression or the clonal evolution of GLs,
      this gene inactivation proving stable even on tumor recurrence.

PMID- 17525681
TI  - Primary Ewing sarcoma of the brain: a case report and literature review.
AB  - Ewing sarcoma, along with peripheral primitive neuroectodermal tumor, belongs to
      a tumor family that shares clinicopathologic and molecular genetic features,
      including the characteristic chromosomal translocation that results in the fusion
      of the EWS gene on 22q12 to either the FLI1 gene on 11q24 or other Ets family
      transcription factor gene, such as the ERG gene on 21q22. In contrast, such
      translocations are not found in central primitive neuroectodermal tumors
      (cPNETs), such as medulloblastoma and supratentorial PNET. Ewing sarcoma has only
      rarely been noted to primarily involve the central nervous system-extraosseous
      Ewing sarcoma (CNS-EES). We report a case of a 7-year-old girl with an anterior
      cranial fossa mass. Pathology showed a primitive small blue cell tumor with focal
      Homer Wright rosette formation. The positive membranous immunostaining for CD99
      and the EWS-FLI1 fusion demonstrated by fluorescence in situ hybridization
      studies confirmed the diagnosis of CNS-EES. Although CNS-EES may look identical
      to cPNETs, these tumors differ in histogenesis, molecular characteristics, and
      clinical behavior. Demonstration of characteristic translocations by molecular
      studies differentiates CNS-EES from cPNET and help clinicians make informed
      decisions regarding therapy.

PMID- 17525682
TI  - Detection of the C282Y and H63D polymorphisms associated with hereditary
      hemochromatosis using the ABI 7500 fast real time PCR platform.
AB  - Classic hereditary hemochromatosis is an autosomal recessive disorder
      characterized by iron overload and sequence variants in the HFE gene. The HFE
      gene is located at 6p21.3 and contains 2 common single nucleotide polymorphisms
      (SNPs) C282Y and H63D, which are routinely tested for in the molecular
      diagnostics laboratory. In this study, we used DNA samples from 59 patients in
      which clinicians wanted to confirm or rule-out hereditary hemochromatosis that
      had been previously tested for the HFE SNPs using a polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) assay and the ABI 7700 real
      time PCR assay with a MGB Eclipse ASR Probe system. The new assay used TAQman SNP
      Genotyping Assays, which were performed on the ABI 7500 FAST real time PCR
      platform. Allelic discrimination was determined during a postamplification plate
      read. Of the 59 samples genotyped, 7 were homozygous for C282Y, 6 were
      heterozygous for C282Y, 9 were homozygous for H63D, 10 were heterozygous for
      H63D, 6 were compound heterozygotes, and 20 were wild type. With the exception of
      one sample that was indeterminate by the TAQman SNP Genotyping Assay, all others
      showed 100% concordance between the 3 assays. The one indeterminate sample was
      heterozygous for C282Y by the PCR-RFLP and ABI 7700 real time PCR assays, but
      there was an insufficient quantity of DNA to perform the TAQman SNP Genotyping
      Assay. Our study suggests that the ABI 7500 FAST TAQman SNP Genotyping Assay is
      comparable with the PCR-RFLP and ABI 7700 real time PCR methods in detecting and
      characterizing these 2 HFE SNPs. Improved software and thermocycling capabilities
      have resulted in a very robust TAQman assay with the advantage of a much improved
      turn-around-time and throughput.

PMID- 17525683
TI  - False positive results of mitochondrial DNA depletion/deletion due to single
      nucleotide substitutions causing appearance of additional PvuII restriction
      sites.
AB  - Human mitochondrial diseases are usually caused by dysfunction of mitochondrial
      DNA (mtDNA), particularly by point mutations, deletions, or depletions. In
      commonly used procedures for molecular diagnostics of mitochondrial dysfunction,
      one of the first steps is linearization of circular mitochondrial genomes with
      either BamHI or PvuII restriction endonulease, which cuts human mtDNA at a unique
      site. Here, we describe a case of false positive results, which suggested mtDNA
      depletion or a large deletion in a patient's tissue sample. More detailed
      analysis (mtDNA sequencing) revealed that these false positive results were
      caused by the presence of the 12753A>G substitution in the gene coding for NADH
      dehydrogenase subunit 5 (ND5). This substitution results in no change in amino
      acid sequence of the gene product but creates an additional PvuII site.
      Investigating a population of 200 patients not affected by mitochondrial
      diseases, we found an additional case of 12753A>G, and also another substitution,
      12804T>C, which also results in no change in amino acid sequence of ND5 but
      creates an additional PvuII site. A few cases of 12753A>G and 12804T>C
      substitutions were found previously in Asian, American, African, and European
      populations (though they were not reported to date in the MITOMAP), but those
      samples were used in population studies and not tested for mtDNA deletion or
      depletion. Therefore, we present a cautionary report indicating that these mtDNA
      polymorphisms exist in various human populations (and thus, they are panethnic)
      and may cause false positive results of standard molecular analyses, including
      molecular diagnostics, of human mtDNA.

PMID- 17525684
TI  - Profound inhibition of the PCR step of CF V3 multiplex PCR/OLA assay by the use
      of UV-irradiated plastic reaction tubes.
AB  - Supplies, such as bags of plastic reaction tubes, are sometimes left in the
      laminar flow hoods unintentionally while the ultraviolet (UV) lamp is illuminated
      overnight. In addition, UV irradiation is used for sterilization and amplicon
      inactivation to avoid contamination. The oligonucleotide ligation assay (OLA) is
      a unique approach to mutation detection of point mutations, small deletions, and
      small insertions. Recently, we encountered problems with this assay and peak
      heights were much lower or disappeared. After going through systemic trouble
      shooting, we found that profound inhibition of the polymerase chain reaction
      (PCR) step of CF V3 multiplex PCR/OLA assay by the use of UV-irradiated plastic
      reaction tubes. When UV-irradiated tubes used throughout the assay, tubes exposed
      for 8 weeks at 0.7 m from the UV source gave a reduction of 60% and 67% in the
      assay products on the basis of sum of peak heights. Tubes exposed for 3 weeks at
      0.1 m from the UV source totally eliminated assay product yielding no peaks.
      Further experiments showed that the inhibition happened mostly in the PCR step.
      Burgess and Hall had reported that inhibition of PCR of human glyceraldehydes-3
      phosphate dehydrogenase transcripts after UV irradiating the tubes. This showed
      that the inhibition was not assay-specific. The reason that the inhibition of PCR
      was more profound could be due to a multiplex PCR assay and small reaction
      volume. The mechanism of PCR inhibition by UV irradiation is not clear. In
      conclusion, plastic reaction tubes intended for PCR/OLA assays should not be
      exposed to UV.

PMID- 17525686
TI  - The role of adherence to antiretroviral therapy in the management of HIV
      infection.
AB  - Despite multiple studies demonstrating the relation between the success of highly
      active antiretroviral therapy (HAART) and adherence, inadequate adherence
      continues to be one of the most frequent reasons for poor treatment outcomes
      and/or lack of sustained treatment benefits. Interventions targeting patient
      related social and psychologic barriers to adherence and issues related to mental
      health and substance abuse and access to health care may ameliorate their
      negative impact on adherence. Specific drug-related factors that influence
      adherence such as pill burden, dosing frequency, food requirements, and acute
      tolerability and safety concerns, however, are further issues that must be
      considered to optimize adherence. Fortunately, the availability of once-daily and
      coformulated agents with simple dosing requirements may help to improve
      adherence, and thereby make the difference between success and failure of HAART
      for some patients. A better understanding of adherence and its determinants and
      how to define specific goals in a given clinical setting are keys for clinicians
      to become more effective partners with patients in the achievement and
      maintenance of long-term virologic suppression and, more importantly, long-term
      health.

PMID- 17525687
TI  - Metabolic issues associated with protease inhibitors.
AB  - Metabolic changes characteristically observed with HIV infection include low
      total and high-density lipoprotein (HDL) cholesterol and elevated triglycerides.
      Initiation of antiretroviral therapy (ART) may increase HDL but may also elevate
      low-density lipoprotein, very-low-density lipoprotein, and triglycerides as well
      as contribute to insulin resistance and morphologic changes (ie, visceral,
      breast, local fat accumulation, subcutaneous fat loss). This may result in a risk
      of cardiovascular disease substantially higher than among age- and sex-matched
      individuals in the general population. Cardiovascular risk calculators, such as
      the Framingham calculators, may underestimate risk in the setting of HIV and
      therapy. The degree of cardiovascular and metabolic risk can be managed with diet
      and lifestyle interventions and lipid-lowering pharmacotherapy, as in the general
      population. In addition, drug selection and treatment switching to agents with
      less impact on metabolic effects can reduce metabolic risk in HIV-positive
      individuals receiving ART.

PMID- 17525691
TI  - Protease inhibitor-based regimens for HIV therapy: safety and efficacy.
AB  - Antiretroviral (ARV) treatment strategies for HIV-infected patients continue to
      evolve. Over the past few years, there was a shift towards the use of
      nonnucleoside reverse transcriptase inhibitor-based regimens, mostly because of
      better tolerability, a lower pill burden, and improved adherence relative to
      using protease inhibitor (PI)-based regimens. Although the 2 strategies do afford
      similar potency and durability, the PI-based regimens provide a higher genetic
      barrier to the development of ARV resistance. This has become progressively more
      important for reasons that include increasing rates of baseline ARV resistance in
      newly infected patients and the risk of developing ARV resistance in treated
      populations with suboptimal adherence. With the introduction of novel ARVs and
      reformulated agents with more convenient dosing requirements, improved
      tolerability, and unique resistance characteristics, boosted PI-based strategies
      are increasingly being considered when initiating therapy in ARV-naive patients.
      In this article, the evidence for the use of boosted PIs as early therapy is
      reviewed, with emphasis on data available from comparative randomized controlled
      trials.

PMID- 17525692
TI  - Assessing the influence of a genetic characteristic on disease in the presence of
      a strong environmental etiology.
AB  - An inference as to the possible causal role of a genetic characteristic in the
      development of a disease is strengthened when there is a large disparity in
      disease incidence between persons with and without that characteristic. If the
      disparity is particularly great when, based on the presence or absence of a
      strong environmental risk factor, we would predict it to be so, then a causal
      inference is further strengthened. Only analyses that focus on the gene-disease
      association, conditional on the environmental factor, directly bear on the
      etiologic role of the genetic characteristic.

PMID- 17525693
TI  - Carbonated beverages and chronic kidney disease.
AB  - BACKGROUND: Carbonated beverage consumption has been linked with diabetes,
      hypertension, and kidney stones, all risk factors for chronic kidney disease.
      Cola beverages, in particular, contain phosphoric acid and have been associated
      with urinary changes that promote kidney stones. METHODS: We examined the
      relationship between carbonated beverages (including cola) and chronic kidney
      disease, using data from 465 patients with newly diagnosed chronic kidney disease
      and 467 community controls recruited in North Carolina between 1980 and 1982.
      RESULTS: Drinking 2 or more colas per day was associated with increased risk of
      chronic kidney disease (adjusted odds ratio = 2.3; 95% confidence interval = 1.4
      3.7). Results were the same for regular colas (2.1; 1.3-3.4) and artificially
      sweetened colas (2.1; 0.7-2.5). Noncola carbonated beverages were not associated
      with chronic kidney disease (0.94; 0.4-2.2). CONCLUSIONS: These preliminary
      results suggest that cola consumption may increase the risk of chronic kidney
      disease.

PMID- 17525694
TI  - Decreasing association between body mass index and blood pressure over time.
AB  - BACKGROUND: Our purpose was to assess blood pressure (BP) and its relationship
      with body mass index (BMI) over a 15-year interval in the Seychelles, a rapidly
      developing country in the African region. METHODS: Two independent cross
      sectional examination surveys were conducted in 1989 (n=1081) and 2004 (n=1255)
      using representative samples of the population age 25-64 years. RESULTS: Between
      1989 and 2004, mean BP (mm Hg) decreased slightly (from 133/87 to 131/86 in men
      and from 127/82 to 124/81 in women), with little change in the age-standardized
      prevalence of high BP (BP >or=140/90 or current treatment; from 45% to 44% in men
      and from 34% to 36% in women). During this same time period, there were marked
      increases in awareness (from 42% to 64%), treatment (22% to 59%), and control (3%
      to 20%) among participants with high BP. The prevalence of overweight (BMI >or=25
      kg/m) increased from 39% to 60%. Furthermore, the linear relationship between BMI
      and BP was markedly weaker in 2004 than in 1989, irrespective of antihypertensive
      treatment and age, and among both lean and overweight participants. Among
      untreated persons, a BMI increment of 1 kg/m was associated with an elevation of
      2.0/1.5 mm Hg of systolic/diastolic BP in 1989 but only 1.3/1.0 mm Hg in 2004.
      CONCLUSIONS: The association between BMI and BP has decreased over time. Further
      study is needed to understand the reasons for the decline in this association,
      and what the implications are in the context of the obesity epidemic.

PMID- 17525695
TI  - Analysis of matched case-control data with incomplete strata: applying
      longitudinal approaches.
AB  - BACKGROUND: Matched case-control data have a structure that is similar to
      longitudinal data with correlated outcomes, except for a retrospective sampling
      scheme. In conditional logistic regression analysis, sets that are incomplete due
      to missing covariates and sets with identical values of the covariates do not
      contribute to the estimation; both situations may cause a loss in efficiency.
      These problems are more severe when sample sizes are small. We evaluated
      retrospective models for longitudinal data as alternatives in analyzing matched
      case-control data. METHODS: We conducted simulations to compare the properties of
      matched case-control data analyses using conditional likelihood and a commonly
      used longitudinal approach generalized estimating equation (GEE). We simulated
      scenarios for one-to-one and one-to-two matching designs, each with various sizes
      of matching strata, with complete and incomplete strata, and with dichotomous and
      normal exposures. RESULTS AND CONCLUSIONS: The simulations show that the
      estimates by conditional likelihood and GEE methods are consistent, and a proper
      coverage was reached for both binary and continuous exposures. The estimates
      produced by conditional likelihood have greater standard errors than those
      obtained by GEE. These relative efficiency losses are more substantial when data
      contain incomplete matched sets and when the data have small sizes of matching
      strata; these can be improved by including more controls in the strata. These
      losses of efficiency also increase as the magnitude of the association increases.

PMID- 17525696
TI  - Women's midlife health across cultures: DAMES comparative analysis.
AB  - OBJECTIVE: The Decisions At Menopause Study (DAMES) investigates the experience
      of menopause in four countries. This article explores self-reported health.
      DESIGN: Women aged 45 to 55 years were interviewed in Lebanon (n=298), Morocco
      (n=299), Spain (n=300), and the United States (n=293). The survey instrument
      included closed- and open-ended questions. Statistical analyses were used to
      assess the determinants of reporting poor health, and textual analyses were used
      to highlight themes related to perceptions of health. RESULTS: In Lebanon and
      Morocco, 22% and 28%, respectively, of the women sampled indicated that their
      health was not good. In Spain and the United States, 15% and 11% of the women
      sampled reported their health as fair or poor. We explored significant predictors
      of poorer reported health across sites. Responses to the open-ended questions
      "How is your health?" and "How do you compare your health to other women your own
      age?" revealed common concerns of aches and pains, tiredness,
      work/responsibilities, and family across all four sites. Unique themes included
      the war in Lebanon, poverty in Morocco, and social activity in Spain. Menopausal
      symptoms may in many cases be overshadowed by other health concerns of middle
      aged women. Nonspecific symptoms such as tiredness and aches and pains serve to
      link bodily health with social circumstances. Family and work responsibilities
      are common concerns of middle-aged women. CONCLUSIONS: Research on midlife health
      and menopause needs to be systematic enough to enable cross-cultural comparisons.
      At the same time, it must be flexible enough to identify population-specific
      symptoms, social context, and lifestyle concerns.

PMID- 17525697
TI  - Down syndrome cell adhesion molecule--a common determinant of brain and heart
      wiring.

PMID- 17525698
TI  - Long term and frequent electrophysiological observation in carpal tunnel
      syndrome.
AB  - AIM: Carpal tunnel syndrome (CTS) is one of the most common compression
      neuropathies in neurology. Electromyography (EMG) including nerve conduction
      study (NCS) is the most useful diagnostic technique for CTS. In this study, we
      aim to demonstrate changes in electrophysiological parameters in different level
      of CTS patients by frequent EMG studies. METHODS: We prospectively followed
      patients with CTS regularly once every 12 weeks for 1 year. Fourteen women (28
      hands) with EMG/NCS findings of CTS were observed and classified in 3 groups
      according to electrophysiological severity. All patients were instructed to wear
      the splint for 12 weeks. At the end of this period, patients were evaluated by
      electrophysiologic parameters. If findings were still abnormal, they were
      encouraged to continue wearing the splint. In severe cases, surgical release was
      carried out. RESULTS: No statistically significant changes were noted in EMG
      recordings of mild cases repeated every 3 months. It was determined that
      significant improvements begin to occur in the moderate group in all parameters,
      except for the amplitude of the median sensory nerve. However, when the mean
      values were studied in the severe CTS group, it was observed that the
      preoperative motor and sensory parameters became increasingly impaired, but
      approached the initial values in the first evaluation in the postoperative
      period. CONCLUSION: Subjects with CTS, particularly moderate as determined by
      electrophysiology, may benefit from conservative therapy, with improvements which
      continue for about one year. In severe cases the main treatment modality seems to
      be operation. Frequent electrophysiological follow-ups may be useful in guiding
      treatment.

PMID- 17525699
TI  - Neck muscle training in the treatment of chronic neck pain: a three-year follow
      up study.
AB  - AIM: The objective of the trial was to evaluate whether the positive results
      achieved with a one-year training regimen in patients with chronic nonspecific
      neck pain would have long-standing effects. METHODS: A follow-up study of two
      neck muscle training groups after a randomized controlled study was carried out.
      One-hundred and eighteen women included were those who had performed neck
      strength and endurance exercises in a previous randomised controlled trial. The
      primary outcome measures were neck pain measured by the visual analogue scale and
      disability indices. Isometric neck strength, range of motion (ROM) and pressure
      pain threshold (PPT) were measured and training frequency for the previous month
      elicited by a questionnaire. RESULTS: At the 3-year follow-up, neck pain and the
      disability indices showed no statistically discernible change compared to the
      situation at the 12-month follow-up. Also, gains in neck strength, ROM and PPT
      achieved during the training year were largely maintained. However, adherence to
      the specific home training program faltered considerably. CONCLUSION: The
      improvements achieved through long-term training were maintained at the 3-year
      follow-up. Since a 12-month exercise programme shows a long-term effect, exercise
      may not need to be performed regularly for the remainder of the subject's life.

PMID- 17525700
TI  - The constraint induced movement therapy: a systematic review of randomised
      controlled trials on the adult stroke patients.
AB  - AIM: The aim of this study was to analyse the evidence of effectiveness on adult
      stroke patients of the Constraint Induced Movement Therapy (CIMT), an original
      rehabilitation method that consists in strongly encouraging patients to use the
      affected arm, mainly immobilising the unaffected arm. METHODS: We only took into
      account the randomised controlled trials on CIMT where the experimental treatment
      was compared with a conventional treatment without any discrepancy of
      organization or session duration. As we could not measure the statistical
      significance of differences between treated and control patients, we compared
      their respective post-treatment percent changes and computed the minimal
      clinically important difference (MCID), defined as a change of at least 10% of
      the maximum score of the scale used. RESULTS: The literature search found 13
      randomised controlled trials (RCTs), 4 of which were excluded because they aimed
      at comparing different intensity of CIMT. The 9 RCTs finally included into the
      review applied the CIMT in either acute, subacute or chronic stroke patients and
      according to different modalities. Findings were positive in all studies, but the
      MCID was reached only in smaller ones, which may have been influenced by
      patients' characteristics. CONCLUSION: Although all studies achieved positive
      results, it is impossible to draw any clear-cut conclusion on the effectiveness
      of the CIMT. The main limitations are the lack of homogeneity in the outcome
      measures used, the inadequacy of data provided and the small samples' size.
      Multicentre studies, using robust outcome measures and considering both motor-
      and sensory-disabled patients are needed.

PMID- 17525701
TI  - Future perspectives in functional neuroimaging in stroke recovery.
AB  - Neurological damage and stroke in particular is the leading cause of long-term
      disability worldwide. Recovery of function after stroke is a consequence of many
      factors including resolution of oedema and survival of the ischaemic penumbra. In
      addition, there is a growing interest in how reorganisation of the surviving
      tissue might subserve the improvements in function that are commonly seen over
      weeks, months, and sometimes years after stroke. Noninvasive techniques such as
      functional magnetic resonance imaging, electroencephalography,
      magnetoencephalography and transcranial magnetic stimulation allow the study of
      this reorganisation in humans. Currently, results suggest that functionally
      relevant reorganisation does occur in cerebral networks in human stroke patients.
      This reorganisation can only occur in structurally and functionally intact brain
      regions. Because these vary depending on the location of the infarction, it is
      likely that different therapeutic strategies will be required to promote
      reorganisation depending on residual functional anatomy. This review maps out the
      attempts to describe functionally relevant adaptive changes in the human brain
      following focal damage. A greater understanding of how these changes are related
      to the recovery process will facilitate the development of novel therapeutic
      techniques designed to minimise impairment based on neurobiological principles
      and how to target these treatments to individual patients.

PMID- 17525702
TI  - Repeated botulinum toxin injections can improve mobility in patients with spinal
      cord lesions.
AB  - AIM: The aim of this study was to increase the knowledge about the response to
      botulinum toxin (BTX) injections to spastic leg muscle motor points (MP) in
      spinal cord lesion (SCL) patients, and describe improvement of mobility with
      repeated BTX injections. METHODS: Six patients with ASIA grade C or D SCL were
      studied at the Loewenstein Rehabilitation Center, Israel. The main outcome
      measures were: modified Ashworth scale scores, range of motion (ROM), and
      mobility spinal cord independence measure (SCIM) scores. BTX was injected twice
      within a few weeks' interval to the MP of spastic leg muscles. The outcome
      measures were monitored before each injection and 2 weeks or more after the
      second injection. RESULTS: Following the first BTX injection the tonus decreased,
      ROM increased in all 6 patients, and mo- bility functioning improved in 4 of
      them. Following the repeated injection the tonus further decrea- sed, ROM further
      improved in 5 of 6 patients, and mobility functions further improved in 4 of 6
      patients. CONCLUSION: BTX can improve mobility in patients with SCL. Repeated
      injections may enhance the effect despite the concern for resistance formation.
      Further research is needed to support the findings and determine the optimal BTX
      doses and intervals between injections.

PMID- 17525703
TI  - Transient activation of transgene expression by hydrodynamics-based injection may
      cause rapid decrease in plasmid DNA expression.
AB  - The intranuclear disposition of exogenous DNA is quite important for the
      therapeutic effects of the administered DNA. The expression efficiency from one
      copy of exogenous DNA delivered by hydrodynamics-based injection dramatically
      decreases over time, and this 'silencing' occurs without CpG methylation. In this
      study, naked luciferase-plasmid DNA was delivered into mouse liver by
      hydrodynamics-based injection, and modifications of the histones bound to the
      plasmid DNA were analyzed by a chromatin immunoprecipitation (ChIP) analysis. In
      addition, the effects of a second hydrodynamics-based injection on the expression
      from the plasmid DNA were examined. The ChIP analysis revealed that the
      modification status of histone H3 remained constant from 4 h to 4 weeks.
      Surprisingly, the injection of saline without DNA enhanced the luciferase
      expression from the preexisting DNA administered 4 and 14 days previously. Our
      results suggest that histone modification plays no role in the silencing.
      Instead, our data suggest that the transgene expression is activated by the
      hydrodynamics-based injection manipulation, and that the return from the
      activated status causes the silencing.

PMID- 17525704
TI  - Nacystelyn enhances adenoviral vector-mediated gene delivery to mouse airways.
AB  - Adenoviral vector-mediated gene delivery has been vastly investigated for cystic
      fibrosis (CF) gene therapy; however, one of its drawbacks is the low efficiency
      of gene transfer, which is due to basolateral colocalization of viral receptors,
      immune responses to viral vectors and the presence of a thick mucus layer in the
      airways of CF patients. Therefore, enhancement of gene transfer can lead to
      reduction in the viral dosage, which could further reduce the acute toxicity
      associated with the use of adenoviral vectors. Nacystelyn (NAL) is a mucolytic
      agent with anti-inflammatory and antioxidant properties, and has been used
      clinically in CF patients to reduce mucus viscosity in the airways. In this
      study, we show that pretreatment of the airways with NAL followed by
      administration of adenoviral vectors in complex with DEAE-Dextran can
      significantly enhance gene delivery to the airways of mice without any harmful
      effects. Moreover, NAL pretreatment can reduce the airway inflammation, which is
      normally observed after delivery of adenoviral particles. Taken together, these
      results indicate that NAL pretreatment followed by adenoviral vector-mediated
      gene delivery can be beneficial to CF patients by increasing the efficiency of
      gene transfer to the airways, and reducing the acute toxicity associated with the
      administration of adenoviral vectors.

PMID- 17525705
TI  - Susceptibility to severe Streptococcal sepsis: use of a large set of isogenic
      mouse lines to study genetic and environmental factors.
AB  - Variation in responses to pathogens is influenced by exposure history,
      environment and the host's genetic status. We recently demonstrated that human
      leukocyte antigen class II allelic differences are a major determinant of the
      severity of invasive group A streptococcal (GAS) sepsis in humans. While in-depth
      controlled molecular studies on populations of genetically well-characterized
      humans are not feasible, it is now possible to exploit genetically diverse panels
      of recombinant inbred BXD mice to define genetic and environmental risk factors.
      Our goal in this study was to standardize the model and identify genetic and
      nongenetic covariates influencing invasive infection outcomes. Despite having
      common ancestors, the various BXD strains (n strains=33, n individuals=445)
      showed marked differences in survival. Mice from all strains developed bacteremia
      but exhibited considerable differences in disease severity, bacterial
      dissemination and mortality rates. Bacteremia and survival showed the expected
      negative correlation. Among nongenetic factors, age -- but not sex or weight --
      was a significant predictor of survival (P=0.0005). To minimize nongenetic
      variability, we limited further analyses to mice aged 40-120 days and calculated
      a corrected relative survival index that reflects the number of days an animal
      survived post-infection normalized to all significant covariates. Genetic
      background (strain) was the most significant factor determining susceptibility
      (P< or =0.0001), thus underscoring the strong effect of host genetic variation in
      determining susceptibility to severe GAS sepsis. This model offers powerful
      unbiased forward genetics to map specific quantitative trait loci and networks of
      pathways modulating the severity of GAS sepsis.

PMID- 17525706
TI  - Association of single nucleotide polymorphisms in endothelin family genes with
      the progression of atherosclerosis in patients with essential hypertension.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictive peptide and its activity is
      mediated by the receptors ET type A (EDNRA) and ET type B (EDNRB). Although ET-1
      is thought to play an important role in the development of atherosclerosis, it
      remains unclear whether polymorphisms of ET-1 family genes, including the ET-1
      gene (EDN1), EDNRA, EDNRB and the genes for endothelin converting enzymes 1 and 2
      (ECE1 and ECE2), are associated with the progression of atherosclerosis. We
      investigated the relationship between 11 single nucleotide polymorphisms (SNPs)
      of ET-1 family genes (including three in EDN1, one in EDNRA, two in EDNRB, four
      in ECE1 and one in ECE2) and atherosclerotic changes assessed using pulse wave
      velocity (PWV) and carotid ultrasonography in 630 patients with essential
      hypertension (EHT). In male subjects, we found significant differences in
      brachial-ankle PWV (baPWV) in additive and recessive models in EDNRB-rs5351 after
      Bonferroni correction. Also in male subjects, there were significant differences
      in mean intima-media thickness (IMT) in additive and recessive models in EDNRA
      rs5333 after Bonferroni correction. We found no significant correlation between
      any SNPs in the ET family genes and baPWV, IMT and Plaque score (PS) in female
      subjects. Furthermore, after multiple logistic regression analysis, only EDNRB
      rs5351 indicated as an independent risk of atherosclerosis in male hypertensive
      subjects. Of the endothelin-related genes, EDNRB-rs5351 was the most susceptible
      SNP associated with atherosclerosis in male hypertensives, and the genetic
      background may be involved in the progression of atherosclerosis in EHT patients.

PMID- 17525707
TI  - Atrial natriuretic peptide (ANP) gene promoter variant and increased
      susceptibility to early development of hypertension in humans.
AB  - Previous evidence supports a role of atrial natriuretic peptide (ANP) as a
      candidate gene for hypertension. We characterized an ANP gene promoter variant,
      which has been associated with lower peptide levels, in a sample of young male
      subjects from Southern Italy (n=395, mean age=35.2+/-2 years) followed up for 28
      years. In this cohort, the ANP gene variant was associated with early blood
      pressure increase and predisposition to develop hypertension.

PMID- 17525708
TI  - Cardiac structure and function and arterial circulation in hypertensive patients
      with and without metabolic syndrome.
AB  - High blood pressure (BP) is one of the crucial determinants of the metabolic
      syndrome (MS). The extent to which MS, diagnosed according to the criteria of the
      International Federation of Diabetes, impacts on cardiovascular organ damage,
      independently of BP, is debated. Three hundred and forty hypertensive patients
      and 100 normotensive controls underwent the following procedures: (1) physical
      examination and resting BP measurements, (2) 24 h ambulatory BP monitoring, (3)
      laboratory routine examination, (4) echocardiography, (5) carotid ultrasonography
      and (6) ankle-brachial BP index. The syndrome was found in 104 of the 340
      hypertensive patients (30.6). In comparison to those without MS, those with MS
      had significantly higher prevalence of left ventricular (LV) hypertrophy by
      mass/height(2.7) criteria (46 vs 42%, P<0.01) but not by LV mass/body surface
      criteria (30 vs 31%); the ratio between early-to-late peak velocities of the LV
      filling waves (E/A) was higher (E/A=0.99+/-0.14 vs 0.89+/-0.15, P<0.01) and left
      atrium was larger (3.8+/-0.3 vs 3.5+/-0.5 cm, P<0.01). Both hypertensive groups
      had significantly greater LVM and carotid intima-media thickness than
      normotensives, without between-group-difference. In this hypertension outpatient
      clinic almost one-third hypertensive patients have MS. They show a deterioration
      in structure and function of the heart in comparison to hypertensive patients
      without MS, but no difference was detected in the carotid and peripheral arterial
      circulation.

PMID- 17525710
TI  - Tranexamic acid and uremic bleeding: evidence-based treatment recommendations.

PMID- 17525713
TI  - Why are rheumatologists treating lupus nephritis?

PMID- 17525714
TI  - Management of growth retardation in pediatric recipients of renal allografts.
AB  - Growth retardation frequently accompanies chronic kidney disease in children.
      Unfortunately, this retardation persists in magnitude despite assiduous
      therapeutic efforts, adequate dialytic intervention, and successful
      transplantation. The age of the patient at transplantation, allograft function,
      and corticosteroid dosage are the major factors that contribute to persistent
      suboptimal growth following renal transplantation. Recent data indicate that the
      use of recombinant human growth hormone might efficaciously improve growth
      velocity in the persistently growth-retarded allograft recipient. Attainment of
      optimum final adult height is predicated on optimum height at the time of
      transplantation, persistent optimum allograft function, minimization or avoidance
      of corticosteroid treatment, and, possibly, use of recombinant human growth
      hormone, especially to potentially maximize the pubertal growth spurt.

PMID- 17525715
TI  - The genetics of IgA nephropathy.
AB  - IgA nephropathy is the most common form of primary glomerulonephritis. Variations
      in clinical manifestations indicate that a diagnosis of IgA nephropathy
      encompasses multiple disease subsets that cannot be distinguished on the basis of
      renal pathology or clinical variables alone. Familial forms of the disease have
      been reported throughout the world, but are probably under-recognized because
      associated urinary abnormalities are often intermittent in affected family
      members. IgA nephropathy has complex determination, with different genes probably
      causing disease in different patient subgroups. Of the many pathogenic mechanisms
      reported, defects in IgA1 glycosylation that lead to formation of immune
      complexes have been consistently implicated. Here, we present the evidence for
      genetic contributions to the disease, review clinical patterns of familial
      disease, and summarize some of the most promising genetic studies conducted to
      date. Linkage-based approaches to the study of familial forms of the disease have
      identified significant or suggestive loci on chromosomes 6q22-23, 2q36, 4q26-31,
      17q12-22 and 3p24-23, but no causal gene has yet been identified. Many
      interesting, but poorly replicated, genetic association studies have also been
      reported. We discuss recent developments in analytic tools that should enable
      genetic studies of sporadic forms of disease by the genome-wide association
      approach.

PMID- 17525716
TI  - Hypothesis--haptoglobin genotype and diabetic nephropathy.
AB  - Vascular complications cause serious morbidity in patients with diabetes
      mellitus. Three such complications are nephropathy, retinopathy and accelerated
      atherosclerotic cardiovascular disease. There is currently scant evidence of a
      genetic marker that predicts which patients will have vascular complications.
      Oxidative stress has an important role in the development of diabetic vascular
      complications. Haptoglobin (Hp) is a hemoglobin-binding protein that has a major
      role in protecting against heme-driven oxidative stress. There are two common
      alleles for Hp (1 and 2) and, therefore, three common Hp genotypes: Hp 1-1, Hp 2
      1, and Hp 2-2. The antioxidant protection provided by Hp is genotype-dependent;
      the protein encoded by Hp 1-1 provides superior antioxidant protection compared
      with that encoded by Hp 2-2. We have shown that diabetic individuals with Hp 2-2
      are more likely to develop nephropathy, retinopathy, and cardiovascular disease
      than those with the Hp 2-1 or Hp 1-1 genotypes.

PMID- 17525717
TI  - Pseudotumor of gout in the patella of a kidney transplant recipient.
AB  - BACKGROUND: A 33-year-old renal transplant recipient presented with painless
      swelling of the right knee. Physical examination revealed an impressive knee
      joint effusion with no signs of inflammation. The patient did not remember a
      recent trauma, but he mentioned a strain 3 years earlier; radiographic findings
      had been normal at that time. The patient had suffered from end-stage renal
      disease due to chronic glomerulonephritis and had previously undergone two
      transplantations. At presentation, his kidney function was stable under treatment
      with ciclosporin, azathioprine and steroids. INVESTIGATIONS: Conventional
      radiography revealed a tumor at the superolateral pole of the right patella.
      Extensive soft tissue invasion and bone destruction was seen on MRI. A knee
      arthroscopy with biopsy, performed to aid diagnosis, showed extensive
      chondrocalcinosis macroscopically; histologically, gouty tophi were found.
      DIAGNOSIS: Pseudotumor of gout in the patella. MANAGEMENT: Uric-acid-lowering
      therapy with benzbromarone was started immediately after diagnosis. A local
      arthroscopic debridement of the right knee joint was performed 4 months later,
      and the patient remained asymptomatic for the next 3 years.

PMID- 17525718
TI  - MN1 overexpression is an important step in the development of inv(16) AML.
AB  - The gene encoding the transcriptional co-activator MN1 is the target of the
      reciprocal chromosome translocation (12;22)(p13;q12) in some patients with acute
      myeloid leukemia (AML). In addition, expression array analysis showed that MN1
      was overexpressed in AML specified by inv(16), in some AML overexpressing
      ecotropic viral integration 1 site (EVI1) and in some AML without karyotypic
      abnormalities. Here we describe that mice receiving transplants of bone marrow
      (BM) overexpressing MN1 rapidly developed myeloproliferative disease (MPD). This
      BM also generated myeloid cell lines in culture. By mimicking the situation in
      human inv(16) AML, forced coexpression of MN1 and Cbfbeta-SMMHC rapidly caused
      AML in mice. These findings identify MN1 as a highly effective hematopoietic
      oncogene and suggest that MN1 overexpression is an important cooperative event in
      human inv(16) AML.

PMID- 17525719
TI  - Morphometry and mathematical modelling of the capillary-like patterns formed in
      vitro by bone marrow macrophages of patients with multiple myeloma.

PMID- 17525720
TI  - Fludarabine, mitoxantrone and dexamethasone as first-line treatment for T-cell
      large granular lymphocyte leukemia.

PMID- 17525721
TI  - N822 mutation of KIT gene was frequent in pediatric acute myeloid leukemia
      patients with t(8;21) in Japan: a study of the Japanese childhood AML cooperative
      study group.

PMID- 17525722
TI  - Proinflammatory response of human leukemic cells to dsRNA transfection linked to
      activation of dendritic cells.
AB  - Leukemic cells exert immunosuppressive effects that interfere with dendritic cell
      (DC) function and hamper effective antileukemic immune responses. Here, we sought
      to enhance the immunogenicity of leukemic cells by loading them with the double
      stranded (ds) RNA Toll-like receptor 3 (TLR3) ligand polyriboinosinic
      polyribocytidylic acid (poly(I:C)), mimicking viral infection of the tumor cells.
      Given the responsiveness of DC to TLR ligands, we hypothesized that the uptake of
      poly(I:C)-loaded leukemic cells by immature DC (iDC) would lead to DC activation.
      Primary acute myeloid leukemia (AML) cells and AML cell lines markedly responded
      to poly(I:C) electroporation by apoptosis, upregulation of TLR3 expression,
      enhanced expression of major histocompatibility complex (MHC) and costimulatory
      molecules and by production of type I interferons (IFN). Upon phagocytosis of
      poly(I:C)-electroporated AML cells, DC maturation and activation were induced as
      judged by an increased expression of MHC and costimulatory molecules, production
      of proinflammatory cytokines and an increase of T helper 1 (T(H)1)-polarizing
      capacity. These immune effects were suboptimal when AML cells were passively
      pulsed with poly(I:C), indicating the superiority of poly(I:C) transfection over
      pulsing. Our results demonstrate that poly(I:C) electroporation is a promising
      strategy to increase the immunogenicity of AML cells and to convert iDC into
      activated mature DC following the phagocytosis of AML cells.

PMID- 17525723
TI  - The T1790A BRAF mutation (L597Q) in childhood acute lymphoblastic leukemia is a
      functional oncogene.

PMID- 17525724
TI  - Apoptosis induced by histone deacetylase inhibitors in leukemic cells is mediated
      by Bim and Noxa.
AB  - Several histone deacetylase inhibitors (HDACi), which have recently entered early
      clinical trials, exert their anticancer activity in part through the induction of
      apoptosis although the precise mechanism of this induction is not known.
      Induction of apoptosis by structurally diverse HDACi in primary cells from
      patients with chronic lymphocytic leukemia (CLL) and different leukemic cell
      lines was mediated by the Bcl-2 regulated intrinsic pathway and demonstrated a
      requirement for de novo protein synthesis. A marked time-dependent induction of
      the pro-apoptotic BH3-only proteins, Bim, Noxa and Bmf was observed, which
      preceded the induction of apoptosis. A key role for both Bim and Noxa was
      proposed in HDACi-mediated apoptosis based on our findings that siRNA for Bim and
      Noxa but not Bmf largely prevented the HDACi-induced loss in mitochondrial
      membrane potential, caspase processing and phosphatidylserine externalization.
      Noxa, induced by HDACi, in CLL cells and tumor cell lines, bound extensively to
      Mcl-1, a major anti-apoptotic Bcl-2 family member present in CLL cells. Our data
      strongly suggests that HDACi induce apoptosis primarily through inactivation of
      anti-apoptotic Bcl-2 family members by increases in Bim and Noxa and highlights
      these increases as a potential clinical target for CLL/lymphoma therapy.

PMID- 17525725
TI  - Aberrant marker expression patterns on the CD34+CD38- stem cell compartment in
      acute myeloid leukemia allows to distinguish the malignant from the normal stem
      cell compartment both at diagnosis and in remission.
AB  - Acute myeloid leukemia (AML) is generally regarded as a stem cell disease. In
      CD34-positive AML, the leukemic stem cell has been recognized as CD38 negative.
      This CD34+CD38- population survives chemotherapy and is most probable the cause
      of minimal residual disease (MRD). The outgrowth of MRD causes relapse and MRD
      can therefore serve as a prognostic marker. The key role of leukemogenic
      CD34+CD38- cells led us to investigate whether they can be detected under MRD
      conditions. Various markers were identified to be aberrantly expressed on the
      CD34+CD38- population in AML and high-risk MDS samples at diagnosis, including C
      type lectin-like molecule-1 and several lineage markers/marker-combinations.
      Fluorescent in situ hybridization analysis revealed that marker-positive cells
      were indeed of malignant origin. The markers were neither expressed on normal
      CD34+CD38- cells in steady-state bone marrow (BM) nor in BM after chemotherapy.
      We found that these markers were indeed expressed in part of the patients on
      malignant CD34+CD38- cells in complete remission, indicating the presence of
      malignant CD34+CD38- cells. Thus, by identifying residual malignant CD34+CD38-
      cells after chemotherapy, MRD detection at the stem cell level turned out to be
      possible. This might facilitate characterization of these chemotherapy-resistant
      leukemogenic cells, thereby being of help to identify new targets for therapy.

PMID- 17525726
TI  - The Wilms' tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of
      WT1 expression in normal and leukemic hematopoiesis.
AB  - The Wilms' tumor gene WT1 is overexpressed in most of human leukemias regardless
      of disease subtypes. To characterize the expression pattern of WT1 during normal
      and neoplastic hematopoiesis, we generated a knock-in reporter green fluorescent
      protein (GFP) mouse (WT1(GFP/+)) and assayed for WT1 expression in normal and
      leukemic hematopoietic cells. In normal hematopoietic cells, WT1 was expressed in
      none of the long-term (LT) hematopoietic stem cells (HSC) and very few (<1%) of
      the multipotent progenitor cells. In contrast, in murine leukemias induced by
      acute myeloid leukemia 1 (AML1)/ETO+TEL/PDGFbetaR or BCR/ABL, WT1 was expressed
      in 40.5 or 38.9% of immature c-kit(+)lin(-)Sca-1(+) (KLS) cells, which contained
      a subset, but not all, of transplantable leukemic stem cells (LSCs). WT1
      expression was minimal in normal fetal liver HSCs and mobilized HSCs, both of
      which are stimulated for proliferation. In addition, overexpression of WT1 in
      HSCs did not result in proliferation or expansion of HSCs and their progeny in
      vivo. Thus, the mechanism by which expansion of WT1-expressing cells occurs in
      leukemia remains unclear. Nevertheless, our results demonstrate that the
      WT1(GFP/+) mouse is a powerful tool for analyzing WT1-expressing cells, and they
      highlight the potential of WT1, as a specific therapeutic target that is
      expressed in LSCs but not in normal HSCs.

PMID- 17525727
TI  - Treatment outcome in adults with acute lymphoblastic leukemia: 50% long-term
      disease-free survival.

PMID- 17525728
TI  - Single nucleotide polymorphism arrays complement metaphase cytogenetics in
      detection of new chromosomal lesions in MDS.

PMID- 17525729
TI  - Interstitial del(14)(q) involving IGH: a novel recurrent aberration in B-NHL.

PMID- 17525730
TI  - Immune reconstitution after allogeneic stem cell transplantation with reduced
      intensity conditioning regimens.
AB  - Reduced-intensity conditioning (RIC) regimens have been increasingly used as an
      alternative to conventional myeloablative conditioning (MAC) regimens for elderly
      patients, for patients medically infirm to qualify for conventional allogeneic
      stem cell transplantation (SCT), and for disorders in which traditional MAC-SCT
      are associated with high rates of non-relapse mortality. One of the theoretical
      advantages of RIC-SCT is that it might lend to better immune reconstitution after
      transplantation due to less damage of the thymus, allowing regeneration of naive
      T cells derived from prethymic donor stem cells, and due to the proliferation of
      immunologically competent host T cells that survive the conditioning regimen.
      Although limited, studies comparing immune recovery following RIC and MAC-SCT
      have been insightful. One of the main difficulties of these studies is the
      current spectrum of RIC protocols, which vary considerably in myeloablative and
      immunosuppressive potential, resulting in apparently contradictory findings. In
      spite of this, most reports have shown significant quantitative and/or
      qualitative differences in T- and B-cell reconstitution after RIC-SCT in
      comparison with conventional SCT. This paper will review current knowledge of
      immune reconstitution following RIC-SCT.

PMID- 17525731
TI  - Individual CREB-target genes dictate usage of distinct cAMP-responsive
      coactivation mechanisms.
AB  - CREB is a key mediator of cAMP- and calcium-inducible transcription, where
      phosphorylation of serine 133 in its Kinase-Inducible Domain (KID) is often
      equated with transactivation. Phospho-Ser133 is required for CREB to bind the KIX
      domain of the coactivators CBP and p300 (CBP/p300) in vitro, although the
      importance of this archetype coactivator interaction for endogenous gene
      expression is unclear. Here, we show that the CREB interaction with KIX is
      necessary for only a part of cAMP-inducible transcription and CBP/p300
      recruitment. Surprisingly, individual cAMP-inducible genes with CREB bound at
      their promoters differed in their reliance on KIX and none examined showed
      complete dependence. Alternatively, we found that arginine 314 (Arg314) in the
      CREB basic-leucine zipper (bZIP) domain contributed to CBP/p300 recruitment and
      KIX-independent CREB transactivation function. This implicates Transducer Of
      Regulated CREB (TORC), an unrelated cAMP-responsive coactivator that binds via
      Arg314, and which can bind CBP/p300, in these functions. Interestingly, KIX was
      also required for the full cAMP induction of a gene that did not require CREB.
      Thus, individual CREB-target gene context dictates the relative contribution of
      at least two different cAMP-responsive coactivation mechanisms.

PMID- 17525732
TI  - ATMIN defines an NBS1-independent pathway of ATM signalling.
AB  - The checkpoint kinase ATM (ataxia telangiectasia mutated) transduces genomic
      stress signals to halt cell cycle progression and promote DNA repair in response
      to DNA damage. Here, we report the characterisation of an essential cofactor for
      ATM, ATMIN (ATM INteracting protein). ATMIN interacts with ATM through a C
      terminal motif, which is also present in Nijmegen breakage syndrome (NBS)1. ATMIN
      and ATM co-localised in response to ATM activation by chloroquine and hypotonic
      stress, but not after induction of double-strand breaks by ionising radiation
      (IR). ATM/ATMIN complex disruption by IR was attenuated in cells with impaired
      NBS1 function, suggesting competition of NBS1 and ATMIN for ATM binding. ATMIN
      protein levels were reduced in ataxia telangiectasia cells and ATM protein levels
      were low in primary murine fibroblasts lacking ATMIN, indicating reciprocal
      stabilisation. Whereas phosphorylation of Smc1, Chk2 and p53 was normal after IR
      in ATMIN-deficient cells, basal ATM activity and ATM activation by hypotonic
      stress and inhibition of DNA replication was impaired. Thus, ATMIN defines a
      novel NBS1-independent pathway of ATM signalling.

PMID- 17525733
TI  - The human DNA repair factor XPC-HR23B distinguishes stereoisomeric
      benzo[a]pyrenyl-DNA lesions.
AB  - Benzo[a]pyrene (B[a]P), a known environmental pollutant and tobacco smoke
      carcinogen, is metabolically activated to highly tumorigenic B[a]P diol epoxide
      derivatives that predominantly form N(2)-guanine adducts in cellular DNA.
      Although nucleotide excision repair (NER) is an important cellular defense
      mechanism, the molecular basis of recognition of these bulky lesions is poorly
      understood. In order to investigate the effects of DNA adduct structure on NER,
      three stereoisomeric and conformationally different B[a]P-N(2)-dG lesions were
      site specifically incorporated into identical 135-mer duplexes and their response
      to purified NER factors was investigated. Using a permanganate footprinting
      assay, the NER lesion recognition factor XPC/HR23B exhibits, in each case,
      remarkably different patterns of helix opening that is also markedly distinct in
      the case of an intra-strand crosslinked cisplatin adduct. The different extents
      of helix distortions, as well as differences in the overall binding of XPC/HR23B
      to double-stranded DNA containing either of the three stereoisomeric B[a]P-N(2)
      dG lesions, are correlated with dual incisions catalyzed by a reconstituted
      incision system of six purified NER factors, and by the full NER apparatus in
      cell-free nuclear extracts.

PMID- 17525734
TI  - p140Cap protein suppresses tumour cell properties, regulating Csk and Src kinase
      activity.
AB  - We recently identified p140Cap as a novel adaptor protein, expressed in
      epithelial-rich tissues and phosphorylated upon cell matrix adhesion and growth
      factor treatment. Here, we characterise p140Cap as a novel Src-binding protein,
      which regulates Src activation via C-terminal Src kinase (Csk). p140Cap silencing
      increases cell spreading, migration rate and Src kinase activity. Accordingly,
      increased expression of p140Cap activates Csk, leading to inhibition of Src and
      downstream signalling as well as of cell motility and invasion. Moreover, cell
      proliferation and "in vivo" breast cancer cell growth are strongly impaired by
      high levels of p140Cap, providing the first evidence that p140Cap is a novel
      negative regulator of tumour growth.

PMID- 17525735
TI  - ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from
      Mcl-1 and Bcl-xL.
AB  - The proapoptotic protein Bim is expressed de novo following withdrawal of serum
      survival factors. Here, we show that Bim-/- fibroblasts and epithelial cells
      exhibit reduced cell death following serum withdrawal in comparison with their
      wild-type counterparts. In viable cells, Bax associates with Bcl-2, Bcl-x(L) and
      Mcl-1. Upon serum withdrawal, newly expressed Bim(EL) associates with Bcl-x(L)
      and Mcl-1, coinciding with the dissociation of Bax from these proteins. Survival
      factors can prevent association of Bim with pro-survival proteins by preventing
      Bim expression. However, we now show that even preformed Bim(EL)/Mcl-1 and
      Bim(EL)/Bcl-x(L) complexes can be rapidly dissociated following activation of
      ERK1/2 by survival factors. The dissociation of Bim from Mcl-1 is specific for
      Bim(EL) and requires ERK1/2-dependent phosphorylation of Bim(EL) at Ser(65).
      Finally, ERK1/2-dependent dissociation of Bim(EL) from Mcl-1 and Bcl-x(L) may
      play a role in regulating Bim(EL) degradation, since mutations in the Bim(EL) BH3
      domain that disrupt binding to Mcl-1 cause increased turnover of Bim(EL). These
      results provide new insights into the role of Bim in cell death and its
      regulation by the ERK1/2 survival pathway.

PMID- 17525736
TI  - Preprotein-controlled catalysis in the helicase motor of SecA.
AB  - The cornerstone of the functionality of almost all motor proteins is the
      regulation of their activity by binding interactions with their respective
      substrates. In most cases, the underlying mechanism of this regulation remains
      unknown. Here, we reveal a novel mechanism used by secretory preproteins to
      control the catalytic cycle of the helicase 'DEAD' motor of SecA, the preprotein
      translocase ATPase. The central feature of this mechanism is a highly conserved
      salt-bridge, Gate1, that controls the opening/closure of the nucleotide cleft.
      Gate1 regulates the propagation of binding signal generated at the Preprotein
      Binding Domain to the nucleotide cleft, thus allowing the physical coupling of
      preprotein binding and release to the ATPase cycle. This relay mechanism is at
      play only after SecA has been previously 'primed' by binding to SecYEG, the
      transmembrane protein-conducting channel. The Gate1-controlled relay mechanism is
      essential for protein translocase catalysis and may be common in helicase motors.

PMID- 17525737
TI  - The opposing homeobox genes Goosecoid and Vent1/2 self-regulate Xenopus
      patterning.
AB  - We present a loss-of-function study using antisense morpholino (MO) reagents for
      the organizer-specific gene Goosecoid (Gsc) and the ventral genes Vent1 and
      Vent2. Unlike in the mouse Gsc is required in Xenopus for mesodermal patterning
      during gastrulation, causing phenotypes ranging from reduction of head structures
      including cyclopia and holoprosencephaly-to expansion of ventral tissues in MO
      injected embryos. The overexpression effects of Gsc mRNA require the expression
      of the BMP antagonist Chordin, a downstream target of Gsc. Combined Vent1 and
      Vent2 MOs strongly dorsalized the embryo. Unexpectedly, simultaneous depletion of
      all three genes led to a rescue of almost normal development in a variety of
      embryological assays. Thus, the phenotypic effects of depleting Gsc or Vent1/2
      are caused by the transcriptional upregulation of their opposing counterparts. A
      principal function of Gsc and Vent1/2 homeobox genes might be to mediate a self
      adjusting mechanism that restores the basic body plan when deviations from the
      norm occur, rather than generating individual cell types. The results may shed
      light on the molecular mechanisms of genetic redundancy.

PMID- 17525738
TI  - Identification and characterization of a novel p42.3 gene as tumor-specific and
      mitosis phase-dependent expression in gastric cancer.
AB  - Multiple genetic alterations are attributed to gastric cancer (GC); however, only
      a few critical genes have been identified so far. In this study, we isolated and
      characterized a novel gene p42.3, represented as tumor-specific and mitosis phase
      dependent expression protein in GC cell line BGC823. Our data showed that the
      expression of p42.3 was cell cycle-dependent in GC cell lines. Moreover, p42.3
      was specifically expressed in primary GC tissues but not in the matched normal
      mucosa of stomach, and this gene was expressed in diverse embryonic tissues.
      Furthermore, significant suppression of cell proliferation and tumorigenicity
      were detected and G(2)/M phase arrest was observed in cell line BGC823 depleted
      of p42.3 expression by RNAi technique, and we confirmed the expression changes of
      cyclin B1 and Chk2 following the silence of p42.3. Taken together, we cloned and
      characterized p42.3 gene that was specifically expressed in GC tumors but not in
      normal gastric mucosa, and the gene was associated with M-phase regulation.
      Moreover, p42.3 might be involved in cell proliferation and tumorigenesis;
      therefore, this gene might have potential applications in the diagnosis or
      treatment of GC.

PMID- 17525739
TI  - AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through
      a methylation hotspot of the 0N promoter in prostate cancer cells.
AB  - We reported previously that the loss of expression of estrogen receptor (ER)-beta
      during the development of prostate cancer (PCa) is associated with methylation of
      a CpG island located in the 5'-flanking sequence of the 0N promoter. Three
      methylation hotspots, referred to as centers 1, 2 and 3, were identified in the
      CpG island. In this study, we demonstrated that a 581-bp region with these three
      centers within it is sufficient for the promoter activity in PCa cells. Deletion
      analyses indicated that center 1 (16 bp), with a putative activator protein-2 (AP
      2) binding site, is essential for gene transactivation. Chromatin
      immunoprecipitation assays showed that AP-2alpha occupies a short sequence
      containing center 1. Forced expression of AP-2alpha or -2gamma, but not -2beta,
      increased activity of the ERbeta 0N promoter and the accumulation of mRNA.
      Conversely, siRNA-mediated AP-2alpha and -2gamma knockdown reduced levels of
      ERbeta transcript and promoter activity. Quantitative reverse transcription-PCR
      showed that AP-2alpha and -2gamma are the predominant transcripts expressed in
      PCa cells, and levels of ERbeta transcript correlate with levels of these AP-2
      transcripts among different PCa cell lines. These results provide the first
      evidence that ERbeta is an AP-2-regulated gene. They also support the hypothesis
      that certain cis-acting elements are methylation hotspots susceptible to
      epigenetic modifications during cancer progression.

PMID- 17525740
TI  - The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer
      cells.
AB  - Vascular endothelial growth factor (VEGF) production by stromal fibroblasts plays
      an important role in tumor angiogenesis. However, VEGF is also expressed by
      normal tissue fibroblasts, raising the question of how the VEGF activity of
      fibroblasts is regulated. Here we report that the latent VEGF angiogenic activity
      of fibroblasts is activated by cancer cells, resulting in tumor-selective
      utilization of fibroblast-derived VEGF. Through the production of VEGF, human VA
      13 fibroblasts promote angiogenesis in and growth of human pancreas cancer Capan
      1 xenograft tumors, whereas VA-13 fibroblasts alone do not show significant
      angiogenesis. Treatment of VA-13 fibroblast supernatant with matrix
      metalloproteinase-7 (MMP-7), an extracellular proteinase characteristically
      expressed by cancer cells, elicits endothelial tube formation. This effect is
      abrogated by anti-VEGF antibody or connective tissue growth factor (CTGF), which
      was previously reported to sequester VEGF and be degraded by MMP-7. Suppression
      of MMP-7 in Capan-1 cells abrogates the tumor angiogenic activity of VA-13
      fibroblasts, which is restored by suppression of CTGF in VA-13 fibroblasts. We
      further show that these molecular mechanisms that trigger angiogenesis are
      effective in human primary fibroblasts and human colorectal tissue. These data
      suggest that fibroblasts may store VEGF in a latent state in the extracellular
      environment for urgent use in angiogenesis.

PMID- 17525741
TI  - Inhibition of Hsp90 function by ansamycins causes downregulation of cdc2 and
      cdc25c and G(2)/M arrest in glioblastoma cell lines.
AB  - Ansamycins exert their effects by binding heat shock protein 90 (Hsp90) and
      targeting important signalling molecules for degradation via the proteasome
      pathway. We wanted to study the effect of geldanamycin (GA) and its derivative 17
      allylamino-17-demethoxygeldanamycin (17-AAG) on glioblastoma cell lines. We show
      that these cells are growth inhibited by ansamycins by being arrested in G(2)/M
      and, subsequently, cells undergo apoptosis. The protein levels of cell division
      cycle 2 (cdc2) kinase and cell division cycle 25c (cdc25c) were downregulated
      upon GA and 17-AAG treatment and cdc2 kinase activity was inhibited. However,
      other proteins involved in the G(2)/M checkpoint were not affected. The cdc2 and
      cdc25c mRNA levels did not show significant differences upon ansamycin treatment,
      but the stability of cdc2 protein was reduced. The association of cdc2 and cdc25c
      with p50(cdc37), an Hsp90 co-chaperone, decreased, but the interaction of cdc2
      and cdc25c with the Hsp70 co-chaperone increased after ansamycin treatment.
      Proteasome inhibitors were able to rescue the cdc2 downregulation, but not the
      cdc25c reduction. However, calpain inhibitors were able to rescue the cdc25c
      downregulation, suggesting that cdc25c is proteolysed by calpains in the presence
      of ansamycins, and not by the proteasome. We conclude that ansamycins
      downregulate cdc2 and cdc25c by two different mechanisms.

PMID- 17525742
TI  - IFN-gamma-induced expression of MUC4 in pancreatic cancer cells is mediated by
      STAT-1 upregulation: a novel mechanism for IFN-gamma response.
AB  - MUC4 is a transmembrane mucin, which is aberrantly expressed in pancreatic
      adenocarcinoma with no detectable expression in the normal pancreas. Here, we
      present a novel mechanism of IFN-gamma-induced expression of MUC4 in pancreatic
      cancer cells. Our studies highlight the upregulation of STAT-1 as a basis for
      MUC4 induction and demonstrate that its activation and upregulation by IFN-gamma
      are two distinct, albeit temporally integrated, signalling events that drive the
      selective induction of IRF-1 and MUC4, respectively, within a single cell system.
      The profile of interferon regulatory factor (IRF)-1 gene induction by IFN-gamma
      is consistent with its rapid transactivation by phospho-Y701-STAT-1. In contrast,
      the induction of the MUC4 mucin gene expression is relatively delayed, and occurs
      only in response to an increase in STAT-1 expression. A progressive binding of
      STAT-1 to various gamma-interferon-activated sequences (GAS) in the MUC4 promoter
      is observed in chromatin immunoprecipitation assay, indicating its direct
      association. Stimulation of STAT-1 expression by double-stranded polynucleotides
      or ectopic expression is shown to induce MUC4 expression, without Y701
      phosphorylation of STAT-1. This effect is abrogated by short interfering RNA
      (siRNA)-mediated inhibition of STAT-1 expression, supporting further the
      relevance of STAT-1 in MUC4 regulation. In conclusion, our findings identify a
      novel mechanism for MUC4 regulation in pancreatic cancer cells and unfold new
      perspectives on the foundation of IFN-gamma-dependent gene regulation.

PMID- 17525743
TI  - The p53--Mdm2--HAUSP complex is involved in p53 stabilization by HAUSP.
AB  - The ubiquitin-specific protease HAUSP is a critical component of the p53-Mdm2
      pathway by acting as a specific deubiquitinase for both p53 and Mdm2. Recent
      structural studies have indicated that p53 and Mdm2 bind to the N-terminal TRAF
      like domain of HAUSP in a mutually exclusive manner. To understand the mechanism
      of HAUSP-mediated effects, we have created a p53 mutant that lacks HAUSP binding
      based on the crystal structure analysis. Indeed, this mutant p53 protein can be
      degraded by Mdm2 but fails to interact with HAUSP both in vitro and in vivo.
      Surprisingly, however, we have found that direct interaction between HAUSP and
      p53 is not absolutely required for it to antagonize efficiently Mdm2-mediated
      ubiquitination of p53 and that HAUSP is capable of enzymatically functioning in
      trans on p53 by using Mdm2 as a bridge. Further, we show that a trimeric protein
      complex containing p53, Mdm2 and HAUSP can exist in vivo, despite mutually
      exclusive binding, with Mdm2 serving as a binding mediator for p53 and HAUSP.
      These findings reveal the complication of HAUSP-mediated effects in the p53-Mdm2
      interplay. It also has important implications for the development of novel
      chemotherapeutic compounds aimed at blocking this protein-protein interaction.

PMID- 17525744
TI  - Stem cell-associated genes are extremely poor prognostic factors for soft-tissue
      sarcoma patients.
AB  - Cancer stem cells can play an important role in tumorigenesis and tumor
      progression. However, it is still difficult to detect and isolate cancer stem
      cells. An alternative approach is to analyse stem cell-associated gene
      expression. We investigated the coexpression of three stem cell-associated genes,
      Hiwi, hTERT and survivin, by quantitative real-time-PCR in 104 primary soft
      tissue sarcomas (STS). Multivariate Cox's proportional hazards regression
      analyses allowed correlating gene expression with overall survival for STS
      patients. Coexpression of all three stem cell-associated genes resulted in a
      significantly increased risk of tumor-related death. Importantly, tumors of
      patients with the poorest prognosis were of all four tumor stages, suggesting
      that their risk is based upon coexpression of stem cell-associated genes rather
      than on tumor stage.

PMID- 17525746
TI  - ERBB2 phosphorylation and trastuzumab sensitivity of breast cancer cell lines.
AB  - Breast cancers that overexpress the ERBB2 tyrosine kinase receptor may be treated
      with the recombinant humanized monoclonal anti-ERBB2 antibody trastuzumab
      (herceptin). However, resistance to this targeted therapy is frequent. We have
      determined the response of 18 breast tumor cell lines to trastuzumab and compared
      it with the ERBB2 phosphorylation status using antibodies directed against
      tyrosine residue 1248. We show that sensitivity to trastuzumab is frequently
      associated with the expression of a phosphorylated ERBB2 protein.

PMID- 17525745
TI  - Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline
      mutations associated with craniosynostosis and skeletal dysplasia syndromes.
AB  - Endometrial carcinoma is the most common gynecological malignancy in the United
      States. Although most women present with early disease confined to the uterus,
      the majority of persistent or recurrent tumors are refractory to current
      chemotherapies. We have identified a total of 11 different FGFR2 mutations in
      3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors.
      Mutations were seen primarily in tumors of the endometrioid histologic subtype
      (18/115 cases investigated, 16%). The majority of the somatic mutations
      identified were identical to germline activating mutations in FGFR2 and FGFR3
      that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia,
      achondroplasia and SADDAN syndrome. The two most common somatic mutations
      identified were S252W (in eight tumors) and N550K (in five samples). Four novel
      mutations were identified, three of which are also likely to result in receptor
      gain-of-function. Extensive functional analyses have already been performed on
      many of these mutations, demonstrating they result in receptor activation through
      a variety of mechanisms. The discovery of activating FGFR2 mutations in
      endometrial carcinoma raises the possibility of employing anti-FGFR molecularly
      targeted therapies in patients with advanced or recurrent endometrial carcinoma.

PMID- 17525747
TI  - Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway.
AB  - FDH (10-formyltetrahydrofolate dehydrogenase) is strongly downregulated in tumors
      while its elevation suppresses proliferation of cancer cells and induces p53
      dependent apoptosis. We have previously shown that FDH induces phosphorylation of
      p53 at Ser6, which is a required step in the activation of apoptosis. In the
      present study, we report that FDH-induced p53 phosphorylation is carried out by
      JNK1 and JNK2 (c-Jun N-terminal kinases) working in concert. We have demonstrated
      that FDH induces phosphorylation of JNK1 and JNK2, while treatment of FDH
      expressing cells with JNK inhibitor SP600125, as well as knockdown of JNK1 or
      JNK2 by siRNA, prevents phosphorylation of p53 at Ser6 and protects cells from
      apoptosis. Interestingly, the knockdown of JNK1 abolished phosphorylation of JNK2
      in response to FDH, while knockdown of JNK2 did not prevent JNK1 phosphorylation.
      Pull-down assay with the p53-specific antibody has shown that JNK2, but not JNK1,
      is physically associated with p53. Our studies revealed a novel mechanism in
      which phosphorylation of JNK2 is mediated by JNK1 before phosphorylation of p53,
      and then p53 is directly phosphorylated by JNK2 at Ser6.

PMID- 17525748
TI  - Comparative expression profiling identifies an in vivo target gene signature with
      TFAP2B as a mediator of the survival function of PAX3/FKHR.
AB  - The chromosomal translocation t(2;13), characteristic for the aggressive
      childhood cancer alveolar rhabdomyosarcoma (aRMS), generates the chimeric
      transcription factor PAX3/FKHR with a well known oncogenic role. However, the
      molecular mechanisms mediating essential pathophysiological functions remain
      poorly defined. Here, we used comparative expression profiling of PAX3/FKHR
      silencing in vitro and PAX3/FKHR-specific gene signatures in vivo to identify
      physiologically important target genes. Hereby, 51 activated genes, both novel
      and known, were identified. We also found repression of skeletal muscle-specific
      genes suggesting that PAX3/FKHR blocks further differentiation of aRMS cells.
      Importantly, TFAP2B was validated as direct target gene mediating the anti
      apoptotic function of PAX3/FKHR. Hence, we developed a pathophysiologically
      relevant transcriptional profile of PAX3/FKHR and identified a critical target
      gene for aRMS development.

PMID- 17525749
TI  - Expression profile of skin papillomas with high cancer risk displays a unique
      genetic signature that clusters with squamous cell carcinomas and predicts risk
      for malignant conversion.
AB  - Chemical induction of squamous tumors in the mouse skin induces multiple benign
      papillomas: high-frequency terminally benign low-risk papillomas and low
      frequency high-risk papillomas, the putative precursor lesions to squamous cell
      carcinoma (SCC). We have compared the gene expression profile of twenty different
      early low- and high-risk papillomas with normal skin and SCC. Unsupervised
      clustering of 514 differentially expressed genes (P<0.001) showed that 9/10 high
      risk papillomas clustered with SCC, while 1/10 clustered with low-risk
      papillomas, and this correlated with keratin markers of tumor progression.
      Prediction analysis for microarrays (PAM) identified 87 genes that distinguished
      the two papilloma classes, and a majority of these had a similar expression
      pattern in both high-risk papillomas and SCC. Additional classifier algorithms
      generated a gene list that correctly classified unknown benign tumors as low- or
      high-risk concordant with promotion protocol and keratin profiling. Reduced
      expression of immune function genes characterized the high-risk papillomas and
      SCC. Immunohistochemistry confirmed reduced T-cell number in high-risk
      papillomas, suggesting that reduced adaptive immunity defines papillomas that
      progress to SCC. These results demonstrate that murine premalignant lesions can
      be segregated into subgroups by gene expression patterns that correlate with risk
      for malignant conversion, and suggest a paradigm for generating diagnostic
      biomarkers for human premalignant lesions with unknown individual risk for
      malignant conversion.

PMID- 17525750
TI  - Smell and taste on a high: symposium on chemical senses: from genes to
      perception.

PMID- 17525751
TI  - T(H)1 cells control themselves by producing interleukin-10.
AB  - Inflammatory T helper 1 (T(H)1)-cell responses successfully eradicate pathogens,
      but often also cause immunopathology. To minimize this deleterious side-effect
      the anti-inflammatory cytokine interleukin-10 (IL-10) is produced. Although IL-10
      was originally isolated from T(H)2 cells it is now known to be produced by many
      cell types. Here, we discuss the recent evidence that shows that T(H)1 cells are
      the main source of IL-10 that controls the immune response against Leishmania
      major and Toxoplasma gondii infection.

PMID- 17525752
TI  - Cytokines in the pathogenesis of rheumatoid arthritis.
AB  - Cytokines regulate a broad range of inflammatory processes that are implicated in
      the pathogenesis of rheumatoid arthritis. In rheumatoid joints, it is well known
      that an imbalance between pro- and anti-inflammatory cytokine activities favours
      the induction of autoimmunity, chronic inflammation and thereby joint damage.
      However, it remains less clear how cytokines are organized within a hierarchical
      regulatory network, and therefore which cytokines may be the best targets for
      clinical intervention a priori. Here, we discuss the crucial effector function of
      cytokines in the immunological processes that are central to the pathogenesis of
      rheumatoid arthritis.

PMID- 17525753
TI  - TGFbeta signalling in control of T-cell-mediated self-reactivity.
AB  - In the immune system, transforming growth factor-beta (TGFbeta) affects multiple
      cell lineages by either promoting or opposing their differentiation, survival and
      proliferation. Understanding the cellular mechanisms of TGFbeta-mediated
      regulation is complicated due to a broad distribution of TGFbeta receptors on the
      surface of different immune-cell types. Recent studies using in vivo genetic
      approaches revealed a critical role for TGFbeta signalling in T cells in
      restraining fatal autoimmune lesions. Here, we review recent advances in our
      understanding of a role for TGFbeta signalling in the regulation of T-cell
      differentiation in the thymus and in the periphery, with a particular emphasis on
      TGFbeta-mediated control of self-reactive T cells.

PMID- 17525754
TI  - SOCS proteins, cytokine signalling and immune regulation.
AB  - Suppressor of cytokine signalling (SOCS) proteins are inhibitors of cytokine
      signalling pathways. Studies have shown that SOCS proteins are key physiological
      regulators of both innate and adaptive immunity. These molecules positively and
      negatively regulate macrophage and dendritic-cell activation and are essential
      for T-cell development and differentiation. Evidence is also emerging of the
      involvement of SOCS proteins in diseases of the immune system. In this Review we
      bring together data from recent studies on SOCS proteins and their role in
      immunity, and propose a cohesive model of how cytokine signalling regulates
      immune-cell function.

PMID- 17525755
TI  - The role of junctional adhesion molecules in vascular inflammation.
AB  - Junctional adhesion molecules (JAMs) of the immunoglobulin superfamily are
      important in the control of vascular permeability and leukocyte transmigration
      across endothelial-cell surfaces, by engaging in homophilic, heterophilic and
      lateral interactions. Through their localization on the endothelial-cell surface
      and expression by platelets, JAMs contribute to adhesive interactions with
      circulating leukocytes and platelets. Antibody-blocking studies and studies using
      genetically modified mice have implicated these functions of JAMs in the
      regulation of leukocyte recruitment to sites of inflammation and ischaemia
      reperfusion injury, in growth-factor-mediated angiogenesis, atherogenesis and
      neointima formation. The comparison of different JAM-family members and animal
      models, however, shows that the picture remains rather complex. This Review
      summarizes recent progress and future directions in understanding the role of
      JAMs as 'gate keepers' in inflammation and vascular pathology.

PMID- 17525756
TI  - Primate rights?

PMID- 17525757
TI  - A real red-letter day.

PMID- 17525758
TI  - Scent of a stem cell.

PMID- 17525759
TI  - Studying cortical depression in vivo.

PMID- 17525760
TI  - Pure spillover transmission between neurons.

PMID- 17525761
TI  - What does the habenula tell dopamine neurons?

PMID- 17525764
TI  - Calcium depletion enhances nectin-1 expression and herpes oncolytic therapy of
      squamous cell carcinoma.
AB  - Attenuated, replication-competent, oncolytic herpes simplex virus type 1 (HSV-1)
      are effective at infecting and lysing many human malignancies in preclinical
      studies. Nectin-1 is a cell-surface receptor for HSV-1 envelope glycoprotein D
      (gD) that also forms a component of intercellular adherens junctions (AJs). We
      sought to determine if the disruption of AJs in squamous cell carcinoma (SCC)
      through calcium depletion could be utilized to increase nectin-1 exposure and
      enhance HSV therapy. NV1023 is a single copy gamma(1)34.5-deleted, lacZ
      expressing, oncolytic HSV-1. Calcium depletion caused cell separation and
      increased nectin-1 expression for three SCC cell lines growing at confluence.
      NV1023 viral entry, soluble gD protein binding and NV1023 cytotoxicity were all
      significantly enhanced for these cell lines at low calcium conditions. The
      increase in NV1023 entry at low calcium conditions was abrogated by nectin-1
      antibody blockade. Murine SCC flank tumors treated with
      ethylenediaminetetraacetic acid (EDTA) showed increased nectin-1 expression and
      increased susceptibility to NV1023 infection. Combined NV1023 and EDTA
      intratumoral injections demonstrated significantly enhanced tumor regression as
      compared to NV1023 alone. These findings establish, as proof-of-principle, that
      herpes viral receptor expression may be modulated on cancer cells to enhance
      oncolytic therapy. This strategy might have future application toward improving
      therapy with a variety of herpes vectors.

PMID- 17525765
TI  - Infective crystalline keratopathy secondary to non-tuberculous mycobacterium
      (Mycobacterium abscessus) in a non-traumatized eye.

PMID- 17525766
TI  - Side Saddle cataract surgery for patients unable to lie flat: learning from the
      past.

PMID- 17525767
TI  - A new strategy to replace the natural vitreous by a novel capsular artificial
      vitreous body with pressure-control valve.
AB  - PURPOSE: The current vitreous substitutes such as silicone oil, heavy silicone
      oil, and polymeric gels that are directly injected into vitreous cavity
      frequently cause severe intraocular complications. There is a very urgent need to
      find a more suitable artificial vitreous substitute for pars plana vitrectomy
      (PPV) surgery. METHODS: We have devised a novel capsular artificial vitreous
      using tailor-made silicone rubber elastomer. The novel device was implanted into
      the vitreous cavity of rabbit after PPV and the eye was examined by
      ophthalmoscopy, fundus photography, and tonometry during an 8-week treatment
      period. B-scan ultrasonography, electroretinogram (ERG), and histological studies
      by light microscopy were also performed at the end of 8 weeks. RESULTS: The novel
      artificial vitreous body consists of a thin vitreous-like capsule with a silicone
      tube-valve system. The capsule can be folded and implanted into vitreous cavity
      through 1.5 mm incision on sclera. Physiological balanced solution (PBS) was then
      injected into the capsule and inflated to support retina and control intraocular
      pressure (IOP) through the tube-valve system subsequently fixed under the
      conjunctiva. Experiments using rabbits showed that the novel vitreous body could
      effectively support the retina and apparently induced no significant pathological
      changes in the eye over 8 weeks. CONCLUSION: This approach may provide a new
      research strategy in the vitreous replacement technology. The novel artificial
      vitreous body device can effectively support retina, control IOP, and has good
      biocompatibility. It may be a good alternative to injecting artificial vitreous
      although its tamponade properties and usefulness still have to be proven in
      complex vitreoretinal diseases.

PMID- 17525768
TI  - Estimating the potential impact of using intravitreal angiostatic agents for wet
      macular degeneration on service capacity in a large retinal referral centre.

PMID- 17525769
TI  - Patients' attitudes towards trainee surgeons performing cataract surgery at a
      teaching hospital.
AB  - AIM: To evaluate patients' preferences of surgeon to perform their cataract
      surgery if given a choice between consultant and trainee. METHODS: A
      questionnaire based patient satisfaction survey was conducted in a large
      University Teaching Hospital in the UK. One hundred and eighty patients
      undergoing first eye cataract surgery between January and March 2006 were asked a
      number of set questions on their preferences regarding the surgeon performing the
      operation. Primary outcome measure was the patient's preference for who would
      perform their cataract surgery (consultant or trainee). RESULTS: Overall, 126
      (70%) accepted that trainee surgeons should operate as part of their training.
      Only 102 (81%) of these (57% of the total) would be happy to be operated on
      themselves by a supervised surgical trainee. Ninety-eight (78%) patients objected
      to being operated on by a trainee if they were to be unsupervised. One hundred
      and forty-two (79%) patients stated they would choose to wait longer for their
      surgery if it meant that a consultant would perform their operation. This
      preference was held significantly more strongly among patients who had been
      listed for surgery from a consultant's clinic rather than from the pooled
      'cataract clinic' (P=0.048). One hundred and forty-four (80%) patients thought
      they should be told the name and designation of the surgeon who was to perform
      their operation. CONCLUSIONS: Patients undergoing their first cataract procedure
      appear to have a preference for their named consultant to perform their surgery.
      If 'patient choice' extends to the choice of operating surgeon, then there are
      clear implications for the training of future UK ophthalmologists.

PMID- 17525770
TI  - Evaluation of optic nerve head configuration in various types of optic neuropathy
      with Heidelberg Retina Tomograph.
AB  - PURPOSE: To test whether Heidelberg Retina Tomograph (HRT) is applicable to
      assess the optic nerve head (ONH) configuration of the atrophic phase of non
      glaucomatous optic neuropathy when a default set of the reference plane is used.
      METHODS: Ten eyes with non-arteritic anterior ischaemic optic neuropathy (NAION),
      17 eyes with Leber's hereditary optic neuropathy (LHON), 40 eyes with compressive
      optic neuropathy (CON) owing to chiasmal tumour, and 241 eyes of control
      individuals were examined with HRT using the default reference plane. The global
      values of HRT parameters were evaluated among the groups of patients and
      controls. The sectoral measurements of the eyes with LHON and CON were compared
      with controls. To eliminate the influence of disc size and age on HRT
      measurements, eyes with disc area- and age-matched normal controls were used for
      comparison with eyes with NAION and LHON. RESULTS: Cup parameters in eyes with
      NAION were similar to those in controls. The retinal nerve fibre layer (RNFL)
      thickness was significantly thinner in eyes with NAION than that of controls. The
      eyes with LHON had significantly larger cup parameters, smaller rim volume, and
      thinner mean RNFL thickness than controls. Eyes with CON had significantly larger
      rim area and smaller cup parameters but similar RNFL thickness compared with
      controls. CONCLUSIONS: When the default reference plane is used, HRT can measure
      the ONH configuration in eyes with NAION and LHON as expected. However, caution
      must be made to interpret the parameters obtained from the eyes with CON.

PMID- 17525771
TI  - The use of Medpor coated tear drainage tube in conjunctivodacryocystorhinostomy.
AB  - PURPOSE: To analyse outcomes of lacrimal bypass surgery with the Medpor coated
      tear drainage tube. METHODS: A total of 26 eyes in 26 patients with persistent
      epiphora who failed canaliculoanastomosis and dacryocystorhinostomy were treated
      by the lacrimal bypass surgery with the Medpor coated tear drainage tubes. Ten
      cases of severe obstruction of punctum and canaliculi and 16 cases with both
      upper system and lacrimal sac obstruction comprised this cohort of patients.
      RESULTS: No tube extrusion or displacement was observed after 6-28 months of
      follow-up. Complete or significant resolution of epiphora was achieved in 23/26
      cases (88.5%). Luminal obstruction by debris was noted in nine eyes, ocular
      discomfort in four, improper tube size selection in two, malposition in one,
      infection in one, diplopia in one, corneal abrasion in one, and reflux of
      intranasal secretion into fornix in another. CONCLUSION: Medpor coated tear
      drainage tube offers tube stabilization in minimizing tube extrusion and
      displacement.

PMID- 17525772
TI  - Surveillance of intraocular foreign bodies in the UK.
AB  - AIMS: To estimate the incidence of penetrating injuries with retained intraocular
      foreign bodies (IOFBs) in the United Kingdom, and to provide epidemiological data
      on the aetiology, management, and visual outcome of such injuries. METHODS: Cases
      were identified prospectively by active surveillance through the British
      Ophthalmological Surveillance Unit reporting card system, for the 12-month period
      June 2004 to May 2005 inclusive. Questionnaire data were obtained from UK
      ophthalmologists at presentation and 6 months following presentation. RESULTS:
      Data were available on 97 patients at presentation and 95 patients at follow-up.
      The minimum estimated incidence of IOFBs in the United Kingdom identified in this
      study was 0.16 per 100 000. All patients were male. Hammering was the most common
      mechanism of injury, occurring in 62% of patients. The IOFB was found in the
      anterior segment in 24%, the posterior segment in 73%, and involved both segments
      in 3%. Endophthalmitis was diagnosed in 9% of patients. Best-corrected visual
      acuity of the injured eye at final follow-up was 6/12 or better in 67%, 6/18 to
      6/60 in 11%, and worse than 6/60 in 22%. Prognostic factors for a poor visual
      outcome included poor visual acuity at presentation, prolapse of intraocular
      tissue, development of endophthalmitis, development of retinal detachment, and
      large size of IOFB. CONCLUSIONS: The incidence of IOFB in the United Kingdom
      appears to have reduced compared to previous studies. The majority of patients
      (67%) retain good visual acuity in the injured eye; however, a significant
      minority (22%) sustain long-term severe visual loss.

PMID- 17525773
TI  - Impression cytology of the conjunctival epithelial cells in patients with cystic
      fibrosis.
AB  - PURPOSE: Cystic fibrosis (CF) is the most frequent lethal autosomal recessive
      hereditary disorder. The disease affects all secretory epithelia, including the
      eye, and belongs to the group of ocular surface epithelial diseases, termed
      keratoconjunctivitis sicca or dry eye syndrome. The aim of this study was to
      evaluate goblet cell population and conjunctival epithelial morphology in
      patients with CF. METHODS: A total of 20 CF patients and 20 controls underwent
      conjunctival impression cytology. RESULTS: Impression cytology showed
      conjunctival squamous metaplasia and goblet cell loss in patients with CF.
      CONCLUSION: Reduced goblet cell numbers and squamous metaplasia may be indicative
      of a higher degree of epithelial damage of conjunctival epithelial cells in CF
      patients, and the presence of neutrophils is a strong sign for an inflammatory
      background of this disease.In view of the simple, noninvasive nature of
      impression cytology, this technique may prove to be an important tool for the
      diagnosis and monitoring of dry eye changes in CF patients.

PMID- 17525774
TI  - The effect of hyaluronidase on ultrasound-measured dispersal of local anaesthetic
      following sub-Tenon injection.
AB  - PURPOSE: To determine by B-scan ultrasonography if the addition of hyaluronidase
      affects the dispersal of anaesthetic fluid after sub-Tenon's injection. DESIGN:
      Single-centre prospective randomised double-blind study. MATERIALS AND METHODS:
      We performed a trial in 19 patients who were randomised to receive 5 ml of
      lidocaine 2% alone, or with hyaluronidase 15 IU/ml. A pre-anaesthetic B-scan
      ultrasound was performed followed by a standard infero-nasal sub-Tenon's
      injection. Further B-scan ultrasound studies were performed at 1, 3, and 5 min
      recording depth of local anaesthetic fluid. Data was analysed with Fisher's exact
      test and Student's t-test where appropriate. Results were considered significant
      when P<0.05. RESULTS: The maximum depth of local anaesthetic was significantly
      less in the hyaluronidase group than the control group at 3 and 5 min (0.79
      vs1.65 mm, P-value 0.01 and 0.43 vs1.52 mm, P-value 0.002 respectively). There
      were no statistically significant differences in the akinesia, pain and surgical
      satisfaction scores between the two groups. CONCLUSIONS: The addition of
      hyaluronidase significantly augments the dispersal of local anaesthetic fluid, as
      measured by B-scan ultrasonography.

PMID- 17525775
TI  - On the potential role for interventional pain management in palliative care.

PMID- 17525776
TI  - National drug control policy and prescription drug abuse: facts and fallacies.
AB  - In a recent press release Joseph A. Califano, Jr., Chairman and President of the
      National Center on Addiction and Substance Abuse at Columbia University called
      for a major shift in American attitudes about substance abuse and addiction and a
      top to bottom overhaul in the nation's healthcare, criminal justice, social
      service, and eduction systems to curtail the rise in illegal drug use and other
      substance abuse. Califano, in 2005, also noted that while America has been
      congratulating itself on curbing increases in alcohol and illicit drug use and in
      the decline in teen smoking, abuse and addition of controlled prescription drugs
      opioids, central nervous system depressants and stimulants-have been stealthily,
      but sharply rising. All the statistics continue to show that prescription drug
      abuse is escalating with increasing emergency department visits and unintentional
      deaths due to prescription controlled substances. While the problem of drug
      prescriptions for controlled substances continues to soar, so are the arguments
      of undertreatment of pain. The present state of affairs show that there were 6.4
      million or 2.6% Americans using prescription-type psychotherapeutic drugs
      nonmedically in the past month. Of these, 4.7 million used pain relievers.
      Current nonmedical use of prescription-type drugs among young adults aged 18-25
      increased from 5.4% in 2002 to 6.3% in 2005. The past year, nonmedical use of
      psychotherapeutic drugs has increased to 6.2% in the population of 12 years or
      older with 15.172 million persons, second only to marijuana use and three times
      the use of cocaine. Parallel to opioid supply and nonmedical prescription drug
      use, the epidemic of medical drug use is also escalating with Americans using 80%
      of world's supply of all opioids and 99% of hydrocodone. Opioids are used
      extensively despite a lack of evidence of their effectiveness in improving pain
      or functional status with potential side effects of hyperalgesia, negative
      hormonal and immune effects, addiction and abuse. The multiple reasons for
      continued escalation of prescription drug abuse and overuse are lack of education
      among all segments including physicians, pharmacists, and the public; ineffective
      and incoherent prescription monitoring programs with lack of funding for a
      national prescription monitoring program NASPER; and a reactive approach on
      behalf of numerous agencies. This review focuses on the problem of prescription
      drug abuse with a discussion of facts and fallacies, along with proposed
      solutions.

PMID- 17525777
TI  - Evaluation of lumbar facet joint nerve blocks in the management of chronic low
      back pain: preliminary report of a randomized, double-blind controlled trial:
      clinical trial NCT00355914.
AB  - BACKGROUND: The prevalence of persistent low back pain with the involvement of
      lumbar facet or zygapophysial joints has been described in controlled studies as
      varying from 15% to 45% based on the criteria of the International Association
      for the Study of Pain. Therapeutic interventions utilized in managing chronic low
      back pain of facet joint origin include intraarticular injections, medial branch
      nerve blocks, and neurolysis of medial branch nerves. OBJECTIVE: To determine the
      clinical effectiveness of therapeutic lumbar facet joint nerve blocks in managing
      chronic low back pain of facet joint origin. DESIGN: A prospective, randomized,
      double-blind trial. SETTING: An interventional pain management setting in the
      United States. METHODS: In this preliminary analysis, data from a total of 60
      patients were included, with 15 patients in each of 4 groups. Thirty patients
      were in a non-steroid group consisting of Groups I (control, with lumbar facet
      joint nerve blocks using bupivacaine ) and II (with lumbar facet joint nerve
      blocks using bupivacaine and Sarapin); another 30 patients were in a steroid
      group consisting of Groups III (with lumbar facet joint nerve blocks using
      bupivacaine and steroids) and IV (with lumbar facet joint nerve blocks using
      bupivacaine, Sarapin, and steroids). All patients met the diagnostic criteria of
      lumbar facet joint pain by means of comparative, controlled diagnostic blocks.
      OUTCOME MEASURES: Numeric Rating Scale (NRS) pain scale, the Oswestry Disability
      Index 2.0 (ODI), employment status, and opioid intake. RESULTS: Significant
      improvement in pain and functional status were observed at 3 months, 6 months,
      and 12 months, compared to baseline measurements. The average number of
      treatments for 1 year was 3.7 with no significant differences among the groups.
      Duration of average pain relief with each procedure was 14.8 +/- 7.9 weeks in the
      non-steroid group, and 12.5 +/- 3.3 weeks in the steroid group, with no
      significant differences among the groups. CONCLUSION: Therapeutic lumbar facet
      joint nerve blocks with local anesthetic, with or without Sarapin or steroids,
      may be effective in the treatment of chronic low back pain of facet joint origin.

PMID- 17525778
TI  - Differentiation of thoracic outlet syndrome from treatment-resistant cervical
      brachial pain syndromes: development and utilization of a questionnaire, clinical
      examination and ultrasound evaluation.
AB  - OBJECTIVE: The present study was undertaken to determine which factors
      differentiate patients with a good outcome after treatment for Thoracic Outlet
      Syndrome (TOS) from patients with a poor outcome. METHODS: A total of 85
      patients, who were examined during one year, had at least 6 months of follow up
      after treatment for TOS with either surgery or botulinum chemodenervation.
      RESULTS: Socioeconomic factors of work disability or workers' compensation claims
      did not differentiate treatment-responsive TOS from treatment-resistant cases.
      There was no difference between the 2 groups regarding the presence of anomalous
      anatomy detected by ultrasonography or regarding the presence of subclavian
      artery flow acceleration or occlusion detected by duplex sonography. Several
      factors were noted more frequently in treatment-resistant patients: sensory
      complaints extending beyond lower trunk dermatomes (42% vs. 10%), weakness
      extending beyond lower trunk myotomes (19% vs. 2%), histories of previous non-TOS
      surgery of the neck or upper limbs (50% vs.17%), comorbidities of fibromyalgia or
      complex regional pain syndrome (81% vs. 12%), and depression (35% vs. 10%).
      Treatment-resistant patients complained about more widespread functional
      impairments on a validated Cervical Brachial Symptom Questionnaire (CBSQ) than
      treatment-responsive patients. Resistant cases responded less often to a scalene
      test block (38% vs. 100%), which is designed to simulate the effects of targeted
      treatment. CONCLUSION: In summary, compared to patients with a good outcome after
      targeted treatment, patients with a poor outcome had more diffuse complaints and
      responded less often to a scalene test block.

PMID- 17525779
TI  - Using peripheral stimulation to reduce the pain of C2-mediated occipital
      headaches: a preliminary report.
AB  - BACKGROUND: Peripheral nerve stimulation (PNS) is an accepted treatment for
      neuropathic pain. Recent studies have focused on its potential for relieving
      headache pain. OBJECTIVES: To investigate the effectiveness of PNS in reducing
      occipital headache pain. DESIGN: A prospective, 12-week pilot study involving 11
      patients evaluated before and after implantation of PNS systems to treat C2
      mediated occipital headaches. METHODS: Prior to and at 4 and 12 weeks after
      implantation, patients completed the Short-Form McGill Pain Questionnaire (SF
      MPQ), Visual Analog Scale (VAS), and Present Pain Index (PPI). Patients also
      answered questionnaires and kept diaries to record stimulator use, medication
      consumption, and numbers of headaches. RESULTS: A comparison of pre- and post
      implantation evaluations showed statistically significant declines in scores on
      the SF-MPQ (64%; p = 0.0013), VAS (67%; p < 0.0001), and PPI (68%; p = 0.0009).
      Most patients (91% and 64% respectively) reported reductions in medication use
      and numbers of headaches. Patients also reported a reduction in headache symptoms
      and the impact of headaches on activities. Two adverse events were encountered,
      one due to a loose connection and, the other caused by lead migration.
      CONCLUSIONS: PNS reduced headache pain, headache frequency and medication use.

PMID- 17525780
TI  - Spread of contrast during L4 and L5 nerve root infiltration under fluoroscopic
      guidance.
AB  - BACKGROUND: Lumbar selective nerve root blocks have been performed to establish
      the origin of lumbar radiculopathy in clinically difficult cases. The diagnostic
      ability of selective nerve root blocks remains controversial because of concern
      over potential spread of an injectate onto adjacent structures. OBJECTIVE: To
      investigate the spread of different volumes of water-soluble contrast during L4
      and L5 selective nerve root blocks. DESIGN: Retrospective, observational case
      series. METHODS: Analysis of medical records and X-ray images obtained during L4
      and L5 selective nerve root blocks. RESULTS: During L4 selective nerve root block
      1 ml of contrast spread onto L5 nerve roots in 46.1% of subjects and during L5
      nerve root block 1 ml of contrast spread onto S1 nerve root in 57.7%. There was
      statistically significant difference (p<0.0001) between spread of contrast onto
      the medially located nerve root in the same lumbar segment and nerve roots in the
      lumbar segment above. CONCLUSIONS: Injection of 1 ml of contrast under
      fluoroscopic guidance does not guarantee selective spread of the contrast around
      L4 or L5 nerve roots only. There is also spread toward the more medial nerve root
      in the same spinal segment during L4 and L5 nerve root infiltration. These
      findings suggest that it is possible to differentiate between L4 and L5 nerve
      root pathology using a sequential nerve root blocks under fluoroscopic guidance.

PMID- 17525781
TI  - Hydrocodone use and sensorineural hearing loss.
AB  - BACKGROUND: The hydrocodone/acetaminophen combination is one of the most commonly
      used analgesic preparations. Isolated incidences of suspected association between
      hydrocodone abuse and rapidly progressive hearing loss have been reported. In
      this study, we describe the clinical characteristics of 5 patients presenting
      with progressive hearing loss and a history of hydrocodone use. METHODS: Patients
      presenting with rapidly progressive bilateral hearing loss who had a documented
      history of hydrocodone use were selected for the study. The presentation,
      audiologic findings, associated comorbidities, and treatment outcomes were
      reviewed. RESULTS: All patients displayed rapidly progressive sensorineural
      hearing loss without vestibular symptoms. Hearing loss was asymmetric in 3
      patients at initial presentation, but progressed to profound loss, usually within
      months. Steroid treatment has no effect on the progression of the hearing loss.
      The admitted quantity of hydrocodone consumed ranged from 10 to 300 mg per day.
      Hepatitis C was the most common comorbidity, present in 60% of the patients. All
      patients underwent cochlear implantation with satisfactory results. CONCLUSIONS:
      The chronic use of hydrocodone can be associated with progressive sensorineural
      hearing loss. Successful auditory rehabilitation can be achieved with cochlear
      implantation. Genetic polymorphisms of drug metabolizing enzymes as well as
      associated comorbidities such as hepatitis C infection may be significant in the
      development of hydrocodone ototoxicity, though additional investigations are
      necessary.

PMID- 17525782
TI  - A case of spinal cord stimulation in Raynaud's Phenomenon: can subthreshold
      sensory stimulation have an effect?
AB  - Spinal cord stimulation is currently used to treat a variety of chronic
      intractable painful conditions. We report a case of severe Raynaud's phenomenon
      in the hands refractory to conservative treatment and responsive to diagnostic
      stellate ganglion block that was effectively treated with a spinal cord
      stimulator placed in the cervical epidural space. After capturing the affected
      areas with paresthesias, blood flow in the left hand and fingers significantly
      improved as evidenced by an increase in skin temperature, a change from cyanotic
      to pink appearance and concomitant reduction in pain. Moreover, the patient
      reported that limb ischemia and pain could be managed overnight with stimulation
      intensities that were below sensory perception thresholds. Thus it seems, at
      least in the overnight period, paresthesias were not required to maintain pain
      relief. This case presents a potential divergence between a requirement for
      paresthesias and pain relief in spinal cord stimulation therapy for the treatment
      of Raynaud's phenomenon. The possible role of the sympathetic nervous system in
      this relationship is also discussed.

PMID- 17525783
TI  - Opioid analgesia: perspectives on right use and utility.
AB  - The ability of opioids to effectively and safely control acute and cancer pain
      has been one of several arguments used to support extending opioid treatment to
      patients with chronic pain, against a backdrop of considerable caution that has
      been based upon fears of addiction. Of course, opioids may cause addiction, but
      the "principle of balance" may justify that "...efforts to address abuse should
      not interfere with legitimate medical practice and patient care." Yet, situations
      are increasingly encountered in which opioid-maintained patients are refractory
      to analgesia during periods of pain, or even during the course of chronic
      treatment. The real question is whether analgesic efficacy of opioids can be
      maintained over time. Overall, the evidence supporting long-term analgesic
      efficacy is weak. The putative mechanisms for failed opioid analgesia may be
      related to tolerance or opioid-induced hyperalgesia. Advances in basic sciences
      may help in understanding these phenomena, but the question of whether long-term
      opioid treatment can improve patients' function or quality of life remains a
      broader issue. Opioid side effects are well known, but with chronic use, most
      (except constipation) subside. Still, side effects can negatively affect the
      outcomes and continuity of therapy. This paper addresses 1) what evidence
      supports the long-term utility of opioids for chronic pain; 2) how side effects
      may alter quality of life; 3) the nature of addiction and why it is different in
      pain patients, and 4) on what grounds could pain medication be denied? These
      questions are discussed in light of patients' rights, and warrant balancing
      particular responsibilities with risks. These are framed within the Hippocratic
      tradition of "producing good for the patient and protecting from harm," so as to
      enable 1) more informed clinical decision making, and 2) progress towards right
      use and utility of opioid treatment for chronic pain.

PMID- 17525784
TI  - Ketamine: an introduction for the pain and palliative medicine physician.
AB  - A history of an escalating chronic intractable pain in a patient with
      cryoglobulinemia, vasculitis, and severe cutaneous ulcerations is presented. A
      strategy of progressive, multi-agent, N-methyl-D-aspartate-receptor (NMDA-R)
      blockade that resulted in adequate pain control and a three-fold reduction in
      opioid consumption is described. Diagnostic process of neuropathic pain and the
      role of NMDA-R in the development of hyperalgesia are briefly reviewed.
      Thereafter, existing clinical literature describing the use of Ketamine, a major
      NMDA-R antagonist for management of malignant pain, is reviewed. Lastly, evidence
      based original protocol for intravenous adjuvant Ketamine analgesia for severe
      cancer pain is presented.

PMID- 17525785
TI  - Lumbar retrodiscal transforaminal injection.
AB  - BACKGROUND: Spinal injections are commonly used to treat lumbar radiculitis and
      back pain. Delivery of medication to specific targeted pathology is considered
      important for a successful therapeutic outcome. A variety of routes of injection
      have been devised for epidural injection of corticosteroid. OBJECTIVES: The
      author demonstrates a variation of the transforaminal injection technique. The
      radiographic spread of contrast is described using a more oblique and ventral
      caudad approach in the epidural space "retrodiscal." It is suggested that the
      radiographic findings of this technique for discogenic causes of induced
      radiculitis and/or back pain may yield more precise targeting of putative
      pathologic sources of radiculopathy and back pain in selected patients. METHODS:
      In patients with disc pathology and radiculitis, the anatomy of the lumbar
      epidural space is reviewed for its potential effect on the flow of injectate.
      Contrast spread was documented for lumbar transforaminal injection using a needle
      placement more oblique and behind the disc rather than in the cranial portion.
      Comparison is made to a typical contrast spread of an infra-pedicular placed
      transforaminal injection. RESULTS: Retrodiscal contrast injection results in
      reliable coverage of the retrodiscal region, the exiting nerve at that foraminal
      level and the proximal portion of the transiting segmental neural sleeve.
      CONCLUSIONS: The radiographic findings demonstrate a difference between classic
      infra-pedicular versus retrodiscal transforaminal epidural contrast injection
      patterns, particularly at relatively low volumes. The clinical advantage of one
      technique versus the other should be established in randomized prospective
      studies.

PMID- 17525786
TI  - Pain simulator can improve the training of residents and pain fellows in
      performing pain management procedures.

PMID- 17525787
TI  - Topical lidocaine and epidural bupivacaine/hydromorphone in the treatment of
      complex regional pain syndrome type 2.

PMID- 17525790
TI  - 48 Annual General Conference: ADDRESS BY THE PRESIDENT, DR. FRANCIS ADU-ABABIO AT
      THE OPENING CEREMONY ON FRIDAY, NOVEMBER 10, 2006.

PMID- 17525788
TI  - Request for additional pertinent information regarding 4 extremity stimulation
      coverage from c2 spinal cord stimulation lead placement.

PMID- 17525791
TI  - The effect of acclydine in chronic fatigue syndrome: a randomized controlled
      trial.
AB  - OBJECTIVES: It is unclear whether insulin-like growth factor (IGF) function is
      involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished
      data and reports in patient organization newsletters suggest that Acclydine, a
      food supplement, could be effective in the treatment of CFS by increasing
      biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF
      binding protein (IGFBP) 3 status of CFS patients compared to age- and gender
      matched neighborhood controls, and to assess the effect of Acclydine on fatigue
      severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1
      ratio). DESIGN: A randomized, placebo-controlled, double-blind clinical trial.
      SETTING: Radboud University Nijmegen Medical Centre, The Netherlands.
      PARTICIPANTS: Fifty-seven adult patients who fulfilled the US Centers for Disease
      Control and Prevention criteria for CFS. IGF status of 22 CFS patients was
      compared to that of 22 healthy age- and gender-matched neighborhood control
      individuals. INTERVENTION: Acclydine or placebo for 14 wk. OUTCOME MEASURES:
      Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue
      severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP
      8]), and biologically active IGF1 serum concentrations. Analyses were on an
      intention-to-treat basis. RESULTS: There was no difference in IGF status in 22
      CFS patients compared to healthy age- and gender-matched control individuals.
      Treatment with Acclydine did not result in significant differences compared with
      the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI -4.4
      to +6.5, p = 0.70), SIP-8 +59.1 (95% CI -201.7 to +319.8, p = 0.65), and
      IGFBP3/IGF1 ratio -0.5 (95% CI -2.8 to +1.7, p = 0.63). CONCLUSION: We found no
      differences in IGF1 status in CFS patients compared to healthy matched
      neighborhood controls. In addition, the results of this clinical trial do not
      demonstrate any benefit of Acclydine over placebo in the treatment of CFS.

PMID- 17525792
TI  - Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of
      malaria: a randomized trial.
AB  - OBJECTIVES: To compare the efficacy and safety of artemether-lumefantrine (AL)
      and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum
      malaria in Uganda. DESIGN: Randomized single-blinded clinical trial. SETTING:
      Apac, Uganda, an area of very high malaria transmission intensity. PARTICIPANTS:
      Children aged 6 mo to 10 y with uncomplicated falciparum malaria. INTERVENTION:
      Treatment of malaria with AL or DP, each following standard 3-d dosing regimens.
      OUTCOME MEASURES: Risks of recurrent parasitemia at 28 and 42 d, unadjusted and
      adjusted by genotyping to distinguish recrudescences and new infections. RESULTS:
      Of 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk
      of recurrent falciparum parasitemia was significantly lower for participants
      treated with DP than for those treated with AL after 28 d (11% versus 29%; risk
      difference [RD] 18%, 95% confidence interval [CI] 11%-26%) and 42 d (43% versus
      53%; RD 9.6%, 95% CI 0%-19%) of follow-up. Similarly, the risk of recurrent
      parasitemia due to possible recrudescence (adjusted by genotyping) was
      significantly lower for participants treated with DP than for those treated with
      AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%-12%) and 42 d (6.9% versus
      16%; RD 9.5%, 95% CI 2.8%-16%). Patients treated with DP had a lower risk of
      recurrent parasitemia due to non-falciparum species, development of
      gametocytemia, and higher mean increase in hemoglobin compared to patients
      treated with AL. Both drugs were well tolerated; serious adverse events were
      uncommon and unrelated to study drugs. CONCLUSION: DP was superior to AL for
      reducing the risk of recurrent parasitemia and gametocytemia, and provided
      improved hemoglobin recovery. DP thus appears to be a good alternative to AL as
      first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit
      of artemisinin-based combination therapy in Africa, treatment should be
      integrated with aggressive strategies to reduce malaria transmission intensity.

PMID- 17525793
TI  - A cluster randomized clinical trial to improve prescribing patterns in ambulatory
      pediatrics.
AB  - OBJECTIVES: Having shown previously that an electronic prescription writer and
      decision support system improved pediatric prescribing behavior for otitis media
      in an academic clinic setting, we assessed whether point-of-care delivery of
      evidence could demonstrate similar effects for a wide range of other common
      pediatric conditions. DESIGN: Cluster randomized controlled trial. SETTING: A
      teaching clinic/clinical practice site and a primary care pediatric clinic
      serving a rural and semi-urban patient mix. PARTICIPANTS: A total of 36 providers
      at the teaching clinic/practice site and eight providers at the private primary
      pediatric clinic. INTERVENTION: An evidence-based message system that presented
      real-time evidence to providers based on prescribing practices for acute otitis
      media, allergic rhinitis, sinusitis, constipation, pharyngitis, croup, urticaria,
      and bronchiolitis. OUTCOME MEASURES: The proportion of prescriptions dispensed in
      accordance with evidence. RESULTS: The proportion of prescriptions dispensed in
      accordance with evidence improved four percentage points, from 38% at baseline to
      42% following the intervention. The control group improved by one percentage
      point, from 39% at baseline to 40% at trial's conclusion. The adjusted difference
      between the intervention and control groups was 8% (95% confidence interval 1%,
      15%). Intervention effectiveness did not decrease with time. CONCLUSION: For
      common pediatric outpatient conditions, a point-of-care evidence-based
      prescription writer and decision support system was associated with significant
      improvements in prescribing practices.

PMID- 17525794
TI  - Functional and biological properties of the nuclear receptor coregulator
      PELP1/MNAR.
AB  - Proline-, glutamic acid-, and leucine-rich protein (PELP)1, also known as
      modulator of nongenomic actions of the estrogen receptor (MNAR), is a novel
      nuclear receptor coregulator with a multitude of functions. PELP1/MNAR serves as
      a scaffolding protein that couples various signaling complexes with nuclear
      receptors and participates in genomic and nongenomic functions. Recent data
      suggest that PELP1/MNAR expression is deregulated in several cancers, including
      breast, endometrial, prostate, and ovarian cancer, and that PELP1/MNAR interacts
      with several oncogenes. In this review, we summarize the emerging biological
      properties and functions of PELP1/MNAR.

PMID- 17525796
TI  - Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase
      2, double-blind, randomized, placebo-controlled trial.
AB  - OBJECTIVES: The objective of this trial was to investigate the safety and
      preliminary effectiveness of a daily dose of 300 mg of tenofovir disoproxil
      fumarate (TDF) versus placebo in preventing HIV infection in women. DESIGN: This
      was a phase 2, randomized, double-blind, placebo-controlled trial. SETTING: The
      study was conducted between June 2004 and March 2006 in Tema, Ghana; Douala,
      Cameroon; and Ibadan, Nigeria. PARTICIPANTS: We enrolled 936 HIV-negative women
      at high risk of HIV infection into this study. INTERVENTION: Participants were
      randomized 1:1 to once daily use of 300 mg of TDF or placebo. OUTCOME MEASURES:
      The primary safety endpoints were grade 2 or higher serum creatinine elevations
      (>2.0 mg/dl) for renal function, grade 3 or 4 aspartate aminotransferase or
      alanine aminotransferase elevations (>170 U/l) for hepatic function, and grade 3
      or 4 phosphorus abnormalities (<1.5 mg/dl). The effectiveness endpoint was
      infection with HIV-1 or HIV-2. RESULTS: Study participants contributed 428 person
      years of laboratory testing to the primary safety analysis. No significant
      differences emerged between treatment groups in clinical or laboratory safety
      outcomes. Study participants contributed 476 person-years of HIV testing to the
      primary effectiveness analysis, during which time eight seroconversions occurred.
      Two were diagnosed in participants randomized to TDF (0.86 per 100 person-years)
      and six in participants receiving placebo (2.48 per 100 person-years), yielding a
      rate ratio of 0.35 (95% confidence interval = 0.03-1.93), which did not achieve
      statistical significance. Owing to premature closures of the Cameroon and Nigeria
      study sites, the planned person-years of follow-up and study power could not be
      achieved. CONCLUSION: Daily oral use of TDF in HIV-uninfected women was not
      associated with increased clinical or laboratory adverse events. Effectiveness
      could not be conclusively evaluated because of the small number of HIV infections
      observed during the study.

PMID- 17525795
TI  - Kinases and protein phosphorylation as regulators of steroid hormone action.
AB  - Although the primary signal for the activation of steroid hormone receptors is
      binding of hormone, there is increasing evidence that the activities of cell
      signaling pathways and the phosphorylation status of these transcription factors
      and their coregulators determine the overall response to the hormone. In some
      cases, enhanced cell signaling is sufficient to cause activation of receptors in
      medium depleted of steroids. Steroid receptors are targets for multiple kinases.
      Many of the phosphorylation sites contain Ser/Thr-Pro motifs implicating proline
      directed kinases such as the cyclin-dependent kinases and the mitogen-activated
      kinases (MAPK) in receptor phosphorylation. Although some sites are
      constitutively phosphorylated, others are phosphorylated in response to hormone.
      Still others are only phosphorylated in response to specific cell signaling
      pathways. Phosphorylation of specific sites has been implicated not only in
      overall transcriptional activity, but also in nuclear localization, protein
      stability, and DNA binding. The studies of the roles of phosphorylation in
      coregulator function are more limited, but it is now well established that many
      of them are highly phosphorylated and that phosphorylation regulates their
      function. There is good evidence that some of the phosphorylation sites in the
      receptors and coregulators are targets of multiple signaling pathways. Individual
      sites have been associated both with functions that enhance the activity of the
      receptor, as well as with functions that inhibit activity. Thus, the specific
      combinations of phosphorylations of the steroid receptor combined with the
      expression levels and phosphorylation status of coregulators will determine the
      genes regulated and the biological response.

PMID- 17525797
TI  - Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic
      hedgehog.
AB  - Holoprosencephaly (HPE) is a clinically heterogeneous developmental anomaly
      affecting the CNS and face, in which the embryonic forebrain fails to divide into
      distinct halves. Numerous genetic loci and environmental factors are implicated
      in HPE, but mutation in the sonic hedgehog (Shh) gene is an established cause in
      both humans and mice. As growth arrest-specific 1 (Gas1) encodes a membrane
      glycoprotein previously identified as a Shh antagonist in the somite, we analyzed
      the craniofacial phenotype of mice harboring a targeted Gas1 deletion. Gas1(-/-)
      mice exhibited microform HPE, including midfacial hypoplasia, premaxillary
      incisor fusion, and cleft palate, in addition to severe ear defects; however,
      gross integrity of the forebrain remained intact. These defects were associated
      with partial loss of Shh signaling in cells at a distance from the source of
      transcription, suggesting that Gas1 can potentiate hedgehog signaling in the
      early face. Loss of a single Shh allele in a Gas1(-/-) background significantly
      exacerbated the midline craniofacial phenotype, providing genetic evidence that
      Shh and Gas1 interact. As human GAS1 maps to chromosome 9q21.3-q22, a region
      previously associated with nonsyndromic cleft palate and congenital deafness, our
      results establish GAS1 as a potential locus for several human craniofacial
      malformations.

PMID- 17525798
TI  - Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin
      sensitivity and full antidiabetic effects of thiazolidinediones.
AB  - PPAR gamma is required for fat cell development and is the molecular target of
      antidiabetic thiazolidinediones (TZDs), which exert insulin-sensitizing effects
      in adipose tissue, skeletal muscle, and liver. Unexpectedly, we found that
      inactivation of PPAR gamma in macrophages results in the development of
      significant glucose intolerance plus skeletal muscle and hepatic insulin
      resistance in lean mice fed a normal diet. This phenotype was associated with
      increased expression of inflammatory markers and impaired insulin signaling in
      adipose tissue, muscle, and liver. PPAR gamma-deficient macrophages secreted
      elevated levels of factors that impair insulin responsiveness in muscle cells in
      a manner that was enhanced by exposure to FFAs. Consistent with this, the
      relative degree of insulin resistance became more severe in mice lacking
      macrophage PPAR gamma following high-fat feeding, and these mice were only
      partially responsive to TZD treatment. These findings reveal an essential role of
      PPAR gamma in macrophages for the maintenance of whole-body insulin action and in
      mediating the antidiabetic actions of TZDs.

PMID- 17525799
TI  - Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis
      in vivo.
AB  - Activation of the inhibitor of NF-kappaB kinase/NF-kappaB (IKK/NF-kappaB) system
      and expression of proinflammatory mediators are major events in acute
      pancreatitis. However, the in vivo consequences of IKK activation on the onset
      and progression of acute pancreatitis remain unclear. Therefore, we modulated IKK
      activity conditionally in pancreatic acinar cells. Transgenic mice expressing the
      reverse tetracycline-responsive transactivator (rtTA) gene under the control of
      the rat elastase promoter were generated to mediate acinar cell-specific
      expression of IKK2 alleles. Expression of dominant-negative IKK2 ameliorated
      cerulein-induced pancreatitis but did not affect activation of trypsin, an
      initial event in experimental pancreatitis. Notably, expression of constitutively
      active IKK2 was sufficient to induce acute pancreatitis. This acinar cell
      specific phenotype included edema, cellular infiltrates, necrosis, and elevation
      of serum lipase levels as well as pancreatic fibrosis. IKK2 activation caused
      increased expression of known NF-kappaB target genes, including mediators of the
      inflammatory response such as TNF-alpha and ICAM-1. Indeed, inhibition of TNF
      alpha activity identified this cytokine as an important effector of IKK2-induced
      pancreatitis. Our data identify the IKK/NF-kappaB pathway in acinar cells as
      being key to the development of experimental pancreatitis and the major factor in
      the inflammatory response typical of this disease.

PMID- 17525800
TI  - CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa
      colonization in Crohn disease.
AB  - The ileal mucosa of Crohn disease (CD) patients is abnormally colonized by
      adherent-invasive E. coli (AIEC) that are able to adhere to and invade intestinal
      epithelial cells. Here, we show that CD-associated AIEC strains adhere to the
      brush border of primary ileal enterocytes isolated from CD patients but not
      controls without inflammatory bowel disease. AIEC adhesion is dependent on type 1
      pili expression on the bacterial surface and on carcinoembryonic antigen-related
      cell adhesion molecule 6 (CEACAM6) expression on the apical surface of ileal
      epithelial cells. We report also that CEACAM6 acts as a receptor for AIEC
      adhesion and is abnormally expressed by ileal epithelial cells in CD patients. In
      addition, our in vitro studies show that there is increased CEACAM6 expression in
      cultured intestinal epithelial cells after IFN-gamma or TNF-alpha stimulation and
      after infection with AIEC bacteria, indicating that AIEC can promote its own
      colonization in CD patients.

PMID- 17525801
TI  - Hypothalamic resistin induces hepatic insulin resistance.
AB  - Circulating resistin stimulates endogenous glucose production (GP). Here, we
      report that bi-directional changes in hypothalamic resistin action have dramatic
      effects on GP and proinflammatory cytokine expression in the liver. The infusion
      of either resistin or an active cysteine mutant in the third cerebral ventricle
      (icv) or in the mediobasal hypothalamus stimulated GP independent of changes in
      circulating levels of glucoregulatory hormones. Conversely, central antagonism of
      resistin action markedly diminished the ability of circulating resistin to
      enhance GP. We also report that centrally mediated mechanisms partially control
      resistin-induced expression of TNF-alpha, IL-6, and SOCS-3 in the liver. These
      results unveil what we believe to be a novel site of action of resistin on GP and
      inflammation and suggest that hypothalamic resistin action can contribute to
      hyperglycemia in type 2 diabetes mellitus.

PMID- 17525803
TI  - Sensor biocompatibility: final frontier in bioanalytical measurement.
AB  - Chemical and biosensors operate as direct sample contact systems; as such, the
      response of the biomatrix to their presence is as important as their response to
      the targeted analyte. There needs to be greater research emphasis on the response
      of biofluids to sensors because of the impact on sensor performance. Mainly, this
      is the result of deposited biolayers through the adsorption of colloids and
      proteins, followed by a more complex surface-active system: whole cells. Sensor
      surface engineering and controlled sample presentation through fluidics are
      likely to be able to mitigate some of these effects. Overall there needs to be a
      convergence with rapidly evolving research strategies in biomaterials if sensors
      are to make the full transition from the laboratory to the real world.

PMID- 17525802
TI  - Pancreas-specific RelA/p65 truncation increases susceptibility of acini to
      inflammation-associated cell death following cerulein pancreatitis.
AB  - Activation of the transcription factor NF-kappaB/Rel has been shown to be
      involved in inflammatory disease. Here we studied the role of RelA/p65, the main
      transactivating subunit, during acute pancreatitis using a Cre-loxP strategy.
      Selective truncation of the rela gene in pancreatic exocrine cells led to both
      severe injury of the acinar cells and systemic complications including lung and
      liver damage. Our data demonstrated that expression and induction of the
      protective pancreas-specific acute phase protein pancreatitis-associated protein
      1 (PAP1) depended on RelA/p65. Lentiviral gene transfer of PAP1 cDNA reduced the
      extent of necrosis and infiltration in the pancreata of mice with selective
      truncation of RelA/p65. These results provide in vivo evidence for RelA/p65
      protection of acinar cell death via upregulation of PAP1. Moreover, our data
      underscore the pancreas-specific role of NF-kappaB/Rel and suggest
      multidimensional roles of NF-kappaB/Rel in different cells and contexts during
      inflammation.

PMID- 17525804
TI  - Emerging methods in proteomics: top-down protein characterization by multistage
      tandem mass spectrometry.
AB  - "Top-down" mass spectrometry methods have emerged as an attractive alternative to
      conventional "bottom-up" approaches for the comprehensive characterization of co-
      and post-translational protein modifications. Here we present a brief overview of
      current strategies employed for top-down protein characterization and discuss the
      key technical challenges and solutions associated with their implementation on a
      range of mass spectrometry instrument platforms. For more specific details
      regarding the individual strategies described herein, interested readers are
      referred to the references cited at the end of this article.

PMID- 17525805
TI  - Optical multiple chemical sensing: status and current challenges.
AB  - Multiple optical sensors for chemical species are sensitive, non-toxic and non
      invasive and enable spatially and temporally resolved multianalyte detection.
      Recent advances are highlighted with a focus on fluorescence-based methods and
      the biologically and clinically important analytes oxygen, pH, carbon dioxide and
      temperature. Indicator chemistries such as permeation-selective microbeads and
      nanoparticles allow the production of microscopically homogeneous sensor layers.
      The use of combinations of spectral discrimations along with time-resolved
      monitoring schemes based on luminescence lifetime or intensity-lifetime ratios
      enables all-optical real-time multianalyte determination.

PMID- 17525806
TI  - Real-time monitoring of antibody secretion from B-cells on a microchip stimulated
      with a minute amount of mitogen.
AB  - This paper describes the cultivation of primary cells in a microchamber and the
      real-time monitoring of small amounts of antibody secretion after the
      introduction of a minute amount of stimulus by a microinjector using time
      resolved fluorescence anisotropy analysis.

PMID- 17525808
TI  - PNA-based probe for quantitative chemiluminescent in situ hybridisation imaging
      of cellular parvovirus B19 replication kinetics.
AB  - To allow the ultrasensitive localization and the quantitative detection of
      parvovirus B19 nucleic acids in single infected cells at various times post
      infection, a peptide nucleic acid (PNA)-based in situ hybridisation (ISH) assay
      with chemiluminescent detection has been developed. The assay is based on the use
      of a biotin-labelled PNA probe detected by a streptavidin-linked alkaline
      phosphatase and a chemiluminescent dioxetane phosphate derivative substrate. The
      luminescent signal was quantified and imaged with an ultrasensitive nitrogen
      cooled CCD camera connected to an epifluorescence microscope. The assay was used
      to analyze the parvovirus B19 infection process in cell cultures and to quantify
      the amount of viral nucleic acids at different times after infection. The
      chemiluminescent ISH-PNA assay is characterized by high resolution providing a
      sharp localization of B19 nucleic acids within single cells, with higher
      sensitivity with respect to conventional colorimetric ISH detection. Thanks to
      the high detectability and wide linear range of chemiluminescence detection, an
      objective evaluation of the percentage of infected cells, which reached its
      maximum at 24 h after infection, following a B19 virus infectious cycle could be
      accurately evaluated. Chemiluminescence detection also allowed the quantitative
      analysis of viral nucleic acids at the single-cell level, showing a continuous
      increase of the content of viral nucleic acids in infected cells with time after
      infection. The developed chemiluminescent ISH-PNA assay could thus represent a
      potent tool for the assessment of viral infections and for the quantitative
      evaluation of the virus nucleic acid load of infected cells in virus studies and
      diagnostics.

PMID- 17525807
TI  - Imaging and detection of morphological changes of single cells before and after
      secretion using scanning electrochemical microscopy.
AB  - Images of Human umbilical vein endothelial cells (HUVECs) have been obtained and
      the regulation of cell morphology changes after nitric oxide release has been
      recorded and discerned quantitatively for the first time using scanning
      electrochemical microscopy.

PMID- 17525809
TI  - Surface plasmon resonance as a time-resolved probe of structural changes in
      molecular films: considerations for correlating resonance shifts with adsorbate
      layer parameters.
AB  - Surface plasmon resonance (SPR) spectroscopy is an efficient probe of transient
      structural changes in molecular films. To analyze kinetic SPR data for such
      systems, generally it is necessary to adapt an adequate theoretical framework
      that would allow one to express the measured optical quantities (time-dependent
      shifts of the resonance angle or wavelength) in terms of the structural
      parameters (layer thickness, mass density, or surface coverage) of the sample
      molecules. We present here theoretical calculations and illustrative experimental
      results to address certain essential elements of this type of data analysis for
      transient SPR systems. The phenomenological framework we consider here is based
      on multilayer reflectivity calculations, and can be applied to a broad class of
      systems involving ordered molecular layers on supporting gold films. A typical
      application of these calculations is demonstrated through the analysis of
      specific SPR experiments designed to probe the kinetics of pH-induced structural
      changes in a molecular film of 11-mercaptoundecanoic acid (MUA) on a thin gold
      film.

PMID- 17525810
TI  - Weighted least-squares in calibration: what difference does it make?
AB  - In univariate calibration, an unknown concentration or amount x(0) is estimated
      from its measured response y(0) by comparison with a calibration data set
      obtained in the same way for known x values. The calibration function y = f(x)
      contains parameters obtained from a least-squares (LS) fit of the calibration
      data. Since minimum-variance estimation requires that the data be weighted
      inversely as their true variances, any other weighting leads to predictable
      losses of precision in the calibration parameters and in the estimation of x(0).
      Incorrect weighting also invalidates the apparent standard errors returned by the
      LS calibration fit. Both effects are studied using Monte Carlo calculations. For
      the strongest commonly encountered heteroscedasticity, proportional error
      (sigma(i) proportional, varianty(i)), neglect of weights yields as much as an
      order of magnitude precision loss for x(0) in the small x region, but only
      nominal loss in the calibration mid-range. Use of replicates gives great
      improvement at small x but can underperform unweighted regression in the mid-to
      large x region. Variance function estimation approximates minimum-variance, even
      though the true variance functions are not well reproduced. A relative error test
      applied to the calibration data themselves is predisposed to favor 1/y(2) (or
      1/x(2)) weighting, even if the data are homoscedastic. This predisposition
      weakens when replicate measurements are taken and disappears when the test is
      applied to an independent set of data. The distinction between a priori and a
      posteriori parameter standard errors is emphasized. Where feasible, the a priori
      approach permits reliable assignment of weights, application of a chi(2) test,
      and use of the normal distribution for confidence limits.

PMID- 17525811
TI  - Drop coating deposition Raman spectroscopy of protein mixtures.
AB  - The technique of drop coating deposition Raman (DCDR) spectroscopy has been shown
      to be a highly reproducible and sensitive method of obtaining Raman spectra from
      low concentration protein solutions. This study assesses the ability of DCDR to
      analyse changes in the relative protein concentrations of aqueous tertiary
      protein mixtures, with protein levels similar to that found in human tear fluid.
      The three proteins used to make the mixtures were lysozyme, lactoferrin and
      albumin. The combination of DCDR spectroscopy and principal components analysis
      is found to be sensitive enough to detect small changes in the relative protein
      concentrations, from very small sample volumes (1.5 microl). With certain
      mixtures it was found that the deposition of proteins was not homogeneous across
      the width of the ring, but averaging spectra taken at different positions could
      compensate for this. Principal components regression was able to predict the
      protein concentrations of test solutions with a good degree of accuracy (root
      mean-square errors of prediction of 0.083, 0.112, and 0.082 mg ml(-1) or 8.3,
      11.2 and 8.2% of the mean concentration value, for lysozyme, lactoferrin and
      albumin concentrations respectively). The results of this study suggest that DCDR
      spectroscopy could be a simple, fast, near-patient technique capable of assisting
      the diagnosis of ocular infection.

PMID- 17525812
TI  - Surfactant-coated carbon nanotubes as pseudophases in liquid-liquid extraction.
AB  - The advantages of surfactant-coated carbon nanotubes (CNTs) as coadjutants in
      liquid-liquid extraction are systematically considered. The effect of the CNT
      state (dispersed or suspended in an aqueous medium) is characterized by the
      single-component solid-liquid isotherms exemplified for benzene. Adsorption
      isotherms are obtained by means of a headspace-GC-MS method, the recommended
      instrumental combination when very volatile compounds are involved. Adsorption
      studies are completed using toluene and n-undecane as model analytes of aromatic
      and linear hydrocarbons, respectively. The potential of using dispersed carbon
      nanotubes to improve liquid-liquid extraction is finally evaluated. The liquid
      liquid distribution of the two model analytes between an organic phase (n
      heptane) and the aqueous dispersion of CNTs is studied via batch extraction and
      subsequent analysis of the organic phase by GC-MS. A prospective application of
      this methodology is also given.

PMID- 17525813
TI  - "One-step" simplified electrochemical sensing of TATP based on its acid
      treatment.
AB  - A fast, simple and sensitive electrochemical method for sensing peroxide-based
      explosives based on their acid treatment is reported. The method relies on the
      high electrocatalytic activity of Prussian-blue (PB)-modified electrodes towards
      the acid-generated hydrogen peroxide in the harsh acidic medium (down to pH 0.3)
      used for releasing hydrogen peroxide. Such effective operation of PB
      electrochemical sensors in strongly acidic media eliminates the need for an
      additional neutralization step required in analogous peroxidase-based assays (due
      to acid-induced enzyme deactivation processes). Factors affecting the efficiency
      of the acid pre-treatment of triacetone triperoxide (TATP) have been examined and
      optimized to allow its sensitive measurement down to the 50 ng level within 60 s.
      Chronoamperometric detection of microgram amounts of solid TATP, following a one
      minute acid mixing and placing a 20 microL droplet onto a disposable PB-modified
      screen-printed electrode is illustrated. Similar results were obtained for the
      peroxide explosive hexamethylene triperoxide diamine (HMTD). By greatly
      simplifying the analytical procedure, such an acid-operated "artificial
      peroxidase" electrocatalytic transducer holds great promise for designing "one
      step", user-friendly, miniaturized, cost-effective devices for field screening of
      peroxide explosives.

PMID- 17525814
TI  - Reversible, fluorescence-based optical sensor for hydrogen peroxide.
AB  - The preparation and characterisation are described of a robust, reversible,
      hydrogen peroxide optical sensor, based on the fluorescent quenching of the dye
      ion-pair [Ru(bpy)(3)(2+)(Ph(4)B(-))(2)], by O(2) produced by the catalytic
      breakdown of H(2)O(2), utilizing the inorganic catalyst RuO(2).xH(2)O. The main
      feature of this system is the one-pot formulation of a coating ink that, when
      dried, forms an active single-layer fluorescence-based H(2)O(2) sensor,
      demonstrably capable of detecting H(2)O(2) over the range of 0.01 to 1 M, with a
      relative standard deviation of ca. 4% and a calculated lower limit of detection
      of 0.1 mM. These sensors are sterilisable, using dry-heat, and stable when stored
      over 40 days, without exhibiting any loss in sensitivity or response
      characteristics.

PMID- 17525815
TI  - An electrochemical method for simultaneous detection and identification of
      Escherichia coli, Staphylococcus aureus and Salmonella choleraesuis using a
      glucose oxidase-peroxidase composite biosensor.
AB  - Quantification of bacterial pollution by amperometric detection at 0.0 V of
      glucose consumption at a graphite-Teflon-glucose oxidase-peroxidase-ferrocene
      composite biosensor under flow injection conditions is reported. Using
      Escherichia coli as the model bacterium, the composition of the growing medium
      was optimized. A constant glucose concentration of 4.0 x 10(-4) M was added to
      the culture medium. The relative response to glucose, expressed as the ratio
      between the amperometric signal and the signal at incubation time t = 0
      multiplied by 100, as a function of E. coli concentration, showed a typical
      behaviour. Limits of detection of 6.5 x 10(2) or 6.5 cfu mL(-1) were achieved
      after 3 or 7 h of incubation, respectively, with no pre-concentration step. The
      detection of bacteria did not affect the lifetime of the biosensor. The
      feasibility of the detection of Staphylococcus aureus and Salmonella choleraesuis
      throughout the glucose consumption measurement at the composite biosensor is also
      demonstrated. The capability of bacterial identification by evaluation of
      bacterial growth in the culture medium containing the antibiotics polymyxin B,
      vancomycin, erythromycin, bacitracin, chloramphenicol, tetracycline and
      ciprofloxacin, was investigated. Each micro-organism tested exhibited a different
      antibiotic susceptibility profile, thus suggesting the possibility of bacteria
      differentiation. A rapid methodology for screening of bacteria is proposed.

PMID- 17525816
TI  - Studies of transport and collection characteristics of gaseous mercury in natural
      gases using amalgamation and isotope dilution analysis.
AB  - Transport and collection characteristics were studied for gaseous elemental
      mercury (Hg(0)(g)) in natural gases using newly developed methodology based on
      amalgamation, isotope dilution with permeation tubes and inductively coupled
      plasma mass spectrometry. The study involved different Au-Pt collection tube
      designs, tubing materials and gaseous matrices, including air, natural and sales
      gas, as well as methane and sales gas to which hydrogen sulfide (H(2)S) had been
      added. The Hg(0)(g) capacity of the Au-Pt tubes was determined to 3.5 +/- 0.1
      microg. Blanks and detection limits of gaseous mercury (Hg(g)) were 58 +/- 17 pg
      m(-3) and 50 pg m(-3), respectively, for a 60 L sample volume. For the gases
      tested, added Hg(0)(g) tracers could be collected with 90% or higher efficiency
      at flow rates and volumes of up to 10 L min(-1) and 100 L, respectively. The
      collection efficiency was found to be independent of the type of gas tested, even
      in the presence of H(2)S. However, for the gases containing H(2)S, the apparent
      transport efficiency of added Hg(0)(g) tracers through stainless steel tubing
      varied from 50 to 150% upon changing the temperature from 25 to 100 degrees C.
      The interaction of stainless steel with Hg(0)(g) leading to either a sink, or
      source of Hg, was not observed in the absence of H(2)S, nor was it observed for
      PTFE tubing in the presence of H(2)S. These observations raise questions about
      the applicability of currently used sampling procedures for determination of
      Hg(g) in H(2)S rich natural gases, including the 6978-2 ISO standard method, in
      which stainless steel is a prescribed material for tubing and valves of the
      sampling apparatus.

PMID- 17525817
TI  - Towards a Chinese conception of adolescent development in a migration context.
AB  - Although there are many well-known theories of adolescent development in the
      West, there is a notable lack of theory with empirical support to understand the
      process and outcome of Chinese adolescent development. This paper attempts to
      advance a Chinese conception of adolescent development in a migration context. A
      qualitative study approach was used to explore the experiences and views of 19
      Chinese-Canadian adolescents from Hong Kong and ten of their parents. The
      findings indicate that parents and adolescents co-construct the dominant theme of
      "covert parental control" in the adolescent development process, and the concept
      of "self in relational networks" as the adolescent development outcome. Based on
      the developmental experiences of these Chinese-Canadian adolescents, a culturally
      sensitive model of Chinese adolescent development is proposed. This model
      incorporates culture and migration as two essential components of the framework
      for a theory regarding Chinese adolescent development. It acknowledges the
      experience of Chinese-Canadian immigrants, takes account of the participants'
      personal meanings, and incorporates the indigenous Chinese cultural concepts of
      bao (reciprocity), guan (guidance), and guanxi (relationship).

PMID- 17525818
TI  - Twelve tips for better communication with patients during history-taking.
AB  - Eliciting proper history from a patient is of paramount importance to establish
      an accurate diagnosis and management in medical practice. Good communication
      skill is a prerequisite for an effective physician patient relationship. A
      systematic search of medical literature has been made to formulate a guideline
      for better communication during history taking. The guideline emphasizes on both
      physical environment and emotional encounter and the key points are expressed as
      tips on relevant issues.

PMID- 17525819
TI  - The roles of porous coral sands in initial enrichment of ammonia-oxidizing
      bacteria.
AB  - The purpose of this study was to investigate the roles of coral sands in the
      enrichment and isolation of ammonium-oxidizing bacteria (AOB). We hypothesized
      that the porous coral sands provided additional surface area and nutrients for
      the growth of periphytic AOB. In the present study, an orthogonal test was
      designed to compare the AOB conversion rates of ammonium-nitrogen (NH4+-N) to
      nitrite-nitrogen (NO2--N) among various combinations of culture media. Results
      showed that the conversion of NH4+-N to NO2--N increased significantly when the
      coral sands were added, implying that coral sands were beneficial to the growth
      of AOB. Additions of potassium dihydrogen phosphate (KH2PO4) or sodium
      bicarbonate (NaHCO3) to the media became unnecessary when coral sands were used,
      but the addition of KH2PO4 was needed when the molar nitrogen to phosphorus (N:P)
      ratio reached 10 in the enrichment media using calcium carbonate (CaCO3) powder
      as a calcium source.

PMID- 17525820
TI  - GITR-GITRL system, a novel player in shock and inflammation.
AB  - Glucocorticoid-induced TNFR-Related (GITR) protein is a member of the tumor
      necrosis factor receptor superfamily that modulates acquired and natural immune
      response. It is expressed in several cells and tissues, including T cells,
      natural killer cells, and, at lower levels, in cells of innate immunity. GITR is
      activated by its ligand, GITRL, mainly expressed on antigen presenting and
      endothelial cells. Recent evidence suggests that the GITR/GITRL system
      participates in the development of inflammatory responses, including shock,
      either due to early response of neutrophils and macrophages, or together with
      autoimmune/allergic pathogenesis. The pro-inflammatory role of the GITR/GITRL
      system is due to: 1) modulation of the extravasation process, 2) activation of
      innate immunity cells, 3) activation of effector T cells also favored by partial
      inhibition of suppressor T cells and modulation of dendritic function. This
      review summarizes the in vivo role of the GITR/GITRL system in inflammation and
      shock, explaining the mechanisms responsible for their effects, considering the
      interplay among the different cells of the immune system and transduction
      pathways activated by GITR and GITRL triggering. The hidden aspects about
      GITR/GITRL function, crucial for treatment planning of inflammatory diseases and
      shock by modulation of this system is stressed.

PMID- 17525821
TI  - Prevalence and correlates of depressive symptoms among high school students in
      Hanover, Jamaica.
AB  - The objective of this study was to determine the prevalence of depressive
      symptoms in Jamaican adolescents and examine its association with individual and
      family factors. We used an abbreviated form of the Beck's Depression Inventory II
      (BDI-II) to assess depressive symptoms among 748 students, attending public high
      schools in the parish of Hanover Jamaica. In the analysis, we classified
      adolescents with scores in the upper quartile of the depressive symptom score as
      having depressive symptoms. Multivariate logistic regression was used to
      determine the predictors of depressive symptoms. 14.2% of participants reported
      depressive symptoms. There was association between engagement in sexual activity
      [Odds Ratio (OR) = 1.61, 95% Confidence Interval (CI) = 1.02-2.51], parental
      monitoring of adolescent activity (OR=2.04, 95%CI=1.33 -3.12), maternal affection
      and support (OR= 4.07, 95%CI= 2.62-6.33), and paternal affection and support (OR=
      1.58, 95%CI= 1.05-2.39) with self reported depressive symptoms at the bivariate
      level. In the final model, depressive symptoms was associated with perceived lack
      of maternal affection and support (OR= 4.06, 95%CI= 2.61-6.32) and showed
      marginal association with being sexually experienced (OR= 1.59, 95%CI= 1.00
      2.52). As most homes are female-headed, establishing support systems for the
      mother to take care of their adolescent children may decrease the odds of
      depressive symptoms. Sexually experienced adolescents may require screening for
      depression. Further research is required to fully explore all factors that could
      predispose Jamaican adolescents to depression.

PMID- 17525822
TI  - A prospective longitudinal study of seasonality in African students living in the
      greater Washington, D.C. metropolitan area.
AB  - We conducted a prospective, longitudinal study of seasonality in a vulnerable
      population, i.e., African students who migrated to a temperate climate.
      Consistent with previous cross-sectional studies, we hypothesized lower mood and
      energy, and higher appetite and weight, in fall/winter than in spring/summer.
      Four cohorts of African students attending a year-long nursing school program
      without vacation in Washington, D.C., were assessed monthly for 1 year. Forty
      three subjects (mean age = 33.46 +/- 6.25), consisting of predominantly females
      (76.7%), completed the study. The cohorts began their academic program in
      different seasons (one each in winter, spring, summer, and fall), inherently
      minimizing confounding influences on seasonality, such as academic and
      immigration stress, as well as allowing adjustment for an order effect. At each
      assessment, students completed three 100-mm visual analog scales for mood,
      energy, and appetite, and were weighed on a digital scale. For each standardized
      dependent variable, a repeated measure ANOVA was used and, if a significant
      effect of month was identified, averages for spring/summer and fall/winter were
      compared using paired t-tests. In addition, a mixed model for repeated measures
      was applied to raw (nonstandardized) data. Body weight was significantly higher
      in fall/winter than in spring/summer (p < 0.01). No seasonal differences in mood,
      energy, or appetite were found. Benefiting from certain unique features of our
      cohorts allowing adjustment for order effects, this is the first study to
      identify a seasonal variation in body weight with a peak in winter using
      longitudinal monthly measurements.

PMID- 17525823
TI  - Mood sensitivity to seasonal changes in African college students living in the
      greater Washington D.C. metropolitan area.
AB  - The purpose of this study was to estimate the degree of seasonality and
      prevalence of winter- and summer-type seasonal affective disorder (SAD) in
      African immigrant college students in comparison with African American peers. A
      convenience sample of 246 African immigrants and 599 African Americans studying
      in Washington, D.C. completed the Seasonal Pattern Assessment Questionnaire
      (SPAQ), which was used to calculate a global seasonality score (GSS) and to
      estimate the prevalence of winter- and summer-type SAD. Degree of seasonality was
      related to a complex interaction between having general awareness of SAD,
      ethnicity, and gender. A greater percentage of African students reported
      experiencing a problem with seasonal changes relative to African American
      students, and had summer SAD, but the groups did not differ on GSS and winter
      SAD. African students reported more difficulties with seasonal changes than their
      African American peers, which could represent a manifestation of incomplete
      acclimatization to a higher latitude and temperate climate. As Africans also had
      a greater rate of summer SAD, this argues against acclimatization to heat.

PMID- 17525824
TI  - Digital three-dimensional atlas of quail development using high-resolution MRI.
AB  - We present an archetypal set of three-dimensional digital atlases of the quail
      embryo based on microscopic magnetic resonance imaging (microMRI). The atlases
      are composed of three modules: (1) images of fixed ex ovo quail, ranging in age
      from embryonic day 5 to 10 (e05 to e10); (2) a coarsely delineated anatomical
      atlas of the microMRI data; and (3) an organ system-based hierarchical graph
      linked to the anatomical delineations. The atlas is designed to be accessed using
      SHIVA, a free Java application. The atlas is extensible and can contain other
      types of information including anatomical, physiological, and functional
      descriptors. It can also be linked to online resources and references. This
      digital atlas provides a framework to place various data types, such as gene
      expression and cell migration data, within the normal three-dimensional anatomy
      of the developing quail embryo. This provides a method for the analysis and
      examination of the spatial relationships among the different types of information
      within the context of the entire embryo.

PMID- 17525826
TI  - Homocysteine-induced biochemical stress predisposes to cytoskeletal remodeling in
      stretched endothelial cells.
AB  - Cellular cytoskeletal remodeling reflects alterations in local biochemical and
      mechanical changes in terms of stress that manifests relocation of signaling
      molecules within and across the cell. Although stretching due to load and
      chemical changes by high homocysteine (HHcy) causes cytoskeletal re-arrangement,
      the synergism between stretch and HHcy is unclear. We investigated the
      contribution of HHcy in cyclic stretch-induced focal adhesion (FA) protein
      redistribution leading to cytoskeletal re-arrangement in mouse aortic endothelial
      cells (MAEC). MAEC were subjected to cyclic stretch (CS) and HHcy alone or in
      combination. The redistribution of FA protein, and small GTPases were determined
      by Confocal microscopy and Western blot techniques in membrane and cytosolic
      compartments. We found that each treatment induces focal adhesion kinase (FAK)
      phosphorylation and cytoskeletal actin polymerization. In addition, CS activates
      and membrane translocates small GTPases RhoA with minimal effect on Rac1, whereas
      HHcy alone is ineffective in both GTPases translocation. However, the combined
      effect of CS and HHcy activates and membrane translocates both GTPases. Free
      radical scavenger NAC (N-Acetyl-Cysteine) inhibits CS and HHcy-mediated FAK
      phosphorylation and actin stress fiber formation. Interestingly, CS also
      activates and membrane translocates another FA protein, paxillin in HHcy
      condition. Cytochalasin D, an actin polymerization blocker and PI3-kinase
      inhibitor Wortmannin inhibited FAK phosphorylation and membrane translocation of
      paxillin suggesting the involvement of PI3K pathway. Together our results suggest
      that CS- and HHcy-induced oxidative stress synergistically contribute to small
      GTPase membrane translocation and focal adhesion protein redistribution leading
      to endothelial remodeling.

PMID- 17525827
TI  - Genetic polymorphisms of LMP/TAP gene and hepatitis B virus infection risk in the
      Chinese population.
AB  - Despite the availability of effective vaccines, hepatitis B virus (HBV) infection
      is still commonly seen worldwide. Several reports show that the human major
      histocompatibility complex (MHC) systems were involved in the elimination of HBV
      via the restrictive antigen-processing pathway. We investigate whether LMP/TAP
      gene polymorphisms coded by MHC-II region were associated with HBV infection. A
      total of seven polymorphisms of LMP/TAP gene were identified by polymerase chain
      reaction (PCR) restriction fragment length polymorphism (RFLP) assays. Three
      hundred fifty-six patients and 326 unrelated healthy volunteers were included in
      the case-control study. Of the seven polymorphisms, three of which (LMP7 codons
      145, TAP1 codons 637, and TAP2 codons 651) were observed to have statistically
      significant association with HBV infection (P < 0.05). We analyzed the three
      locus haplotype constructed with three such polymorphisms and found that the
      frequency of haplotypes D and E increased significantly in patients, in
      comparison with that in controls (OR = 3.57, 95% CI: 2.09-6.12, P < 0.001; OR =
      2.74, 95% CI: 1.35-5.56, P = 0.005, respectively). The results imply that LMP7
      145, TAP1-637, and TAP2-651 sites were associated with the risk of HBV infection.
      Haplotypes D and E might be involved in the development of HBV infection. These
      data suggest a potential role of LMP/TAP gene as a candidate gene for
      susceptibility to HBV infection.

PMID- 17525828
TI  - Increased expression of plasma and CD4+ T lymphocyte costimulatory molecule CD26
      in adult patients with allergic asthma.
AB  - CD26, which is a costimulatory molecule and peptidase, is responsible for the
      degradation of interferon (IFN)-gamma-induced chemokines. To elucidate the
      immunopathological role of CD26 in allergic asthma, we investigated plasma
      soluble CD26 (sCD26) concentration and its cell surface expression on
      lymphocytes, monocytes, CD4+ T helper, CD8+ T suppressor plus cytotoxic T,
      invariant natural killer T (iNKT), and CD19+ B lymphocytes in allergic asthmatic
      patients. Plasma sCD26 was significantly elevated in asthmatic patients
      regardless of inhaled corticosteroid treatment (all P < 0.05). Cell surface
      expression of CD26 was significantly up-regulated on lymphocytes, especially on
      CD4+ and iNKT lymphocytes (all P < 0.05), but not on other cell types.
      Significant positive correlations were found between sCD26 and the percentage of
      eosinophils, Th2-related chemokines CCL5 and CCL22, and costimulatory molecule
      sCTLA-4 (all P < 0.05). In conclusion, the aberrant expression of CD26 may
      contribute to the inflammatory process and Th2 predominance in the
      immunopathogenesis of allergic asthma.

PMID- 17525829
TI  - Inhibition of galectin-3 mediated cellular interactions by pectic polysaccharides
      from dietary sources.
AB  - Pectic polysaccharides from dietary sources such as Decalepis hamiltonii--swallow
      root (SRPP), Hemidesmus indicus (HPP), Nigella sativa--black cumin (BCPP),
      Andrographis serpyllifolia-(APP), Zingiber officinale--ginger (GRPP) and, citrus
      pectin (CPP) were examined for galectin inhibitory activity. Inhibition of (a)
      galectin-3 of MDA-MB-231 cells induced hemagglutination of red blood cells; (b)
      galectin-3 mediated interaction between normal/metastatic human buccal cells
      (NBC)/(MBC) and; (c) invasion of MDA-MB-231 and MBC in the invasive chamber was
      assessed. Results indicated that SRPP inhibited hemagglutination at Minimum
      Inhibitory Concentration (MIC) of 1.86 microg ml(-1) equivalent of carbohydrate
      as apposed to those of BCPP (130 microg ml(-1)), APP (40 microg ml(-1)), HPP (40
      microg ml(-1)) and CPP (25 microg ml(-1)). GRPP even at concentration >1-6 mg ml(
      1) did not inhibit agglutination. Also SRPP showed approximately 15 and 2 fold
      potent anti hemagglutination activity relative to that of galectin-3 specific
      sugars-galactose (MIC-27.1 microg ml(-1)) and lactose (MIC-4.16 microg ml(-1))
      respectively. Further, SRPP at 10 microg ml(-1) inhibited agglutination of NBC by
      galectin-3 of MDA-MB-231 cells. Modified swallow root pectic polysaccharide
      (MSRPP) of 50 kDa retained anti hemagglutination activity (MIC of 1.03 microg ml(
      1)) and inhibited MDA-MB-231 and MBC invasion by 73 and 50% with an IC(50) of 136
      and 200 microg ml(-1) respectively. Both SRPP and MSRPP induced apoptosis up to
      80% at 100 microg ml(-1) concentration by activating approximately 2 and 8 folds
      of Caspase-3 activity. Sugar composition analysis and its correlation with the
      galectin inhibitory property indicated that pectic polysaccharides with higher
      arabinose and galactose content-arabinogalactan inhibited hemagglutination
      significantly.

PMID- 17525831
TI  - Application and evaluation of kriging and cokriging methods on groundwater depth
      mapping.
AB  - Groundwater and water resources management play a key role in conserving the
      sustainable conditions in arid and semi-arid regions. Applying some techniques
      that can reveal the critical and hot conditions of water resources seem
      necessary. In this study, kriging and cokriging methods were evaluated for
      mapping the groundwater depth across a plain in which has experienced different
      climatic conditions (dry, wet, and normal) and consequently high variations in
      groundwater depth in a 12 year led in maximum, minimum, and mean depths. During
      this period groundwater depth has considerable fluctuations. Results obtained
      from geostatistical analysis showed that groundwater depth varies spatially in
      different climatic conditions. Furthermore, the calculated RMSE showed that
      cokriging approach was more accurate than kriging in mapping the groundwater
      depth though there was not a distinct difference. As a whole, kriging
      underestimated the real groundwater depth for dry, wet, and normal conditions by
      5.5, 2.2, and 5.3%, while cokriging underestimations were 3.3, 2, and 2.2%,
      respectively; which showed the unbiasedness in estimations. Results implied that
      in the study area farming and cultivation in dry conditions needs more attention
      due to higher variability in groundwater depth in short distances compared to the
      other climate conditions. It is believed that geostatistical approaches are
      reliable tools for water resources managers and water authorities to allocate
      groundwater resources in different environmental conditions.

PMID- 17525830
TI  - Establishment of high-resolution FISH mapping system and its application for
      molecular cytogenetic characterization of chromosomes in newt, Cynops
      pyrrhogaster (Urodela, Amphibia).
AB  - Urodele amphibians (newts and salamanders) are important animal models for
      understanding regeneration mechanisms and genome evolution. We constructed
      ideograms of BrdU/dT- and C-banded karyotypes in the Japanese fire-belly newt,
      Cynops pyrrhogaster, which is useful as a model animal with extremely high
      ability of regeneration. We also established a high-resolution FISH mapping
      system for newts, and localized satellite DNA sequences, 18S rDNAs, telomeric
      (TTAGGG)n repeats and seven functional genes, including genes associated with
      lens regeneration, tyrosinase and two types of gamma crystallins, to chromosomes
      of the newt. The 18S rDNAs were localized to three chromosomal pairs in males,
      whereas the chromosomal locations were highly variable in females. No
      hybridization signals were detected for the telomeric (TTAGGG)n sequence. All
      three lens regeneration-related genes were mapped on the short arm of chromosome
      7, suggesting that the location of the genes in the same linkage group may be
      correlated with the regulation of gene expression associated with chromatin
      dynamics in interphase nuclei during regeneration. The chromosomal distribution
      and nucleotide sequences of pericentric satellite DNA sequences were well
      conserved between C. pyrrhogaster and European newts; in contrast, there was
      species specificity of nucleotide sequences for centromere-specific satellite
      DNAs.

PMID- 17525832
TI  - Heavy metal contents and the water quality of Karasu Creek in Nigde, Turkey.
AB  - Different sources of pollution in Karasu Creek were investigated to obtain the
      water quality and ratio of contamination in this region. To achieve the main
      objectives of the present study, water samples were collected from Karasu Creek,
      starting from flow pattern at the upstream site of Akkaya Dam to the end of the
      dam, crossing the place where the Creek drains into. Dissolved oxygen, electrical
      conductivity, temperature and maximum/minimum pH were measured systematically for
      12 months in the stations, where the water samples were collected. Chemical
      analyses of the water samples were carried out by using Cadas 50 S brand UV
      spectrometer to find out the Pb, Fe, Cu, Zn, Ni, Cr, Cd, S, F and Cn
      concentrations. These concentration were determined in microg/lt as 80-850; 180
      4,920; 10-6,100; 440-25,530; 130-2,400; 120-280; 20-150; 214,250-1,113,580; 1,560
      4,270 and 40-690, respectively. To determine metal levels of the water samples,
      multivariate analyses (element coefficient correlation, coefficient correlation
      dendrogram, hierarchical cluster analysis dendrogram, model summary and ANOVA)
      were used. The analyses yielded highly accurate results. There were positive
      correlations between some elements and their possible sources were the same. The
      stations which resembled each other along the creek were divided into three
      groups. The water quality of the creek was low and had toxic qualities.
      Eutrophication developed in Akkaya Dam along the creek. The source of pollution
      was thought to be industrial and residential wastes. Absolute (0-100 m), short
      distance (100-500 m) and medium distance (500-2,000 m) conservation areas should
      be determined in pollution areas along Karasu Creek and they should be improved.

PMID- 17525834
TI  - Variability and application of the chlorophyll fluorescence emission ratio
      red/far-red of leaves.
AB  - Various approaches to understand and make use of the variable chlorophyll (Chl)
      fluorescence emission spectrum and fluorescence ratio are reviewed. The Chl
      fluorescence of leaves consists of two maxima in the red (near 685-690 nm), and
      far-red region (near 730-740 nm). The intensity and shape of the Chl fluorescence
      emission spectrum of leaves at room temperature are primarily dependent on the
      concentration of the fluorophore Chl a, and to a lower degree also on the leaf
      structure, the photosynthetic activity, and the leaf's optical properties. The
      latter determine the penetration of excitation light into the leaf as well as the
      emission of Chl fluorescence from different depths of the leaf. Due to the re
      absorption mainly of the red Chl fluorescence band emitted inside the leaf, the
      ratio between the red and the far-red Chl fluorescence maxima (near 690 and 730
      740 nm, respectively), e.g., as F690/F735, decreases with increasing Chl content
      in a curvilinear relationship and is a good inverse indicator of the Chl content
      of the leaf tissue, e.g., before and after stress events. The Chl fluorescence
      ratio of leaves can be applied for Chl determinations in basic photosynthesis
      research, agriculture, horticulture, and forestry. It can be used to assess
      changes of the photosynthetic apparatus, developmental processes of leaves, state
      of health, stress events, stress tolerance, and also to detect diseases or N
      deficiency of plants.

PMID- 17525835
TI  - Overexpression of RhoE has a prognostic value in non-small cell lung cancer.
AB  - BACKGROUND: Increasing evidence has suggested that RhoE plays an important role
      in carcinogenesis and progression. However, the correlation between RhoE
      expression and clinical outcome in lung cancer has not been investigated.
      METHODS: RhoE expression was detected by immunohistochemistry on tissue
      microarray containing samples from 115 patients with non-small cell lung cancer
      with a median follow-up of 54 months. RESULTS: RhoE was overexpressed in the
      cytoplasm of lung cancer cells compared with undetectable expression of RhoE in
      the adjacent nontumoral cells. Patients with RhoE-negative tumors had
      substantially longer cancer-related survival than did patients with RhoE-positive
      tumors. Multivariate analysis showed that RhoE overexpression was an independent
      marker for cancer-related survival in the entire population after adjusting for
      other prognostic factors. CONCLUSIONS: RhoE expression may serve as an
      unfavorable prognostic factor in patients with non-small cell lung cancer.

PMID- 17525836
TI  - Resecting lymph nodes in colon cancer: more than a staging operation?

PMID- 17525837
TI  - [Management of accidental hypothermia].
AB  - Patients with hypothermia are frequently encountered in emergency medicine.
      Particularly trauma patients, but also other predisposed persons, can be expected
      to suffer from hypothermia at any time of the year. Therapy focuses not only on
      symptom-oriented intensive care to stabilize and secure vital functions, but also
      on rewarming. Even in cases of severe hypothermia with circulatory arrest,
      therapy can produce excellent results. This paper first gives a brief overview of
      the typical clinical symptoms of hypothermia, before giving a detailed
      description of the preclinical and in-hospital management of the hypothermia
      patient. The various rewarming strategies are the subject of special attention
      and critical evaluation.

PMID- 17525838
TI  - [What is the value of minimizing access trauma for patients?].
AB  - Minimizing the access trauma of surgical interventions is becoming an essential
      task in modern surgery in order to make the treatment more comfortable for the
      patient. Minimally invasive surgery has had a major impact on the improvement of
      surgical results over the last decade. This is why such surgery is often named as
      the third patient friendly revolution in surgery after the introduction of
      asepsis and anesthesia. Operations that caused a huge strain on the patients in
      the past and led to immense costs for society because of the patient's lost
      working time and extensive rehabilitation, have lost their fear thanks to this
      technique. The physical strain is lower, the cosmetic effect is considerable and
      the costs for society might be reduced due to the significantly shorter duration
      of convalescence. Despite its known advantages, which have been reported in
      numerous studies, minimally invasive surgery has recently gained increased
      interest because of the installation of new accounting systems as well as strict
      budgeting and restricted resources. Realistic cost-benefit analysis and
      objectified quality controls are needed in order to guarantee innovative and
      patient friendly basic approaches in medicine in the future.

PMID- 17525839
TI  - [Intracranial tumors in pediatric patients].
AB  - Every year, 400 children suffer from a brain tumor. These are the most frequent
      solid tumors in the pediatric patient. They represent a very heterogenic group of
      tumors with different clinical symptoms, pathology, therapy and prognosis.
      Imaging modalities such as CT and MRI are important for the diagnosis and follow
      up after therapy. Brain tumors in children are responsible for 15-20% of all
      brain tumors. Tumors of the central nervous system are the second most common
      tumors after leukemia. Infra- and supratentorial tumors occur in equal number,
      however, there are differences in the age of occurrence: supratentorial tumors
      occur more often within the first 2-3 years of life, whereas infratentorial
      tumors reach there peak between 4 and 10 years. After the tenth year, infra- and
      supratentorial tumors occur with equal frequency.

PMID- 17525840
TI  - High-mobility group box 1 protein plasma concentrations during septic shock.
AB  - OBJECTIVE: To investigate plasma high-mobility group box 1 protein (HMGB1)
      concentration and its relationship with organ dysfunction and outcome in septic
      shock patients. DESIGN AND SETTING: Prospective, noninterventional study. Medical
      adult intensive care unit at a university hospital in France. PATIENTS: 42
      critically ill patients with septic shock. METHODS: Arterial blood was drawn
      within 12 h of admission for the measurement of plasma HMGB1 concentration by
      ELISA. Repeated sampling was performed on days 3, 7, and 14. RESULTS: Median
      HMGB1 concentration was 4.4 ng/ml (IQR 1.2-12.5) at admission, with no difference
      between survivors and nonsurvivors. A positive correlation was observed between
      HMGB1 and SOFA score and lactate, and procalcitonin concentrations. There was a
      progressive but statistically nonsignificant decline in HMGB1 concentration among
      the survivors, while nonsurvivors showed an increase in HMGB1 level between days
      1 and 3. SOFA score and lactate and procalcitonin concentrations did not vary
      significantly between days 1 and 3. When measured on day 3, HMGB1 discriminated
      survivors from nonsurvivors with 66% sensitivity and 67% specificity, and
      concentration greater than 4 ng/ml was associated with an odds ratio of death of
      5.5 (95% CI 1.3-23.6).

PMID- 17525841
TI  - Agreement of central venous saturation and mixed venous saturation in cardiac
      surgery patients.
AB  - OBJECTIVE: Comparison of the bias and the limits of agreement (LOA; 2 SD) of the
      central venous saturation (S(cv)O(2)) before, during and after coronary artery
      bypass graft surgery with a simultaneous measurement of the mixed venous
      saturation (S(v)O(2)). DESIGN AND SETTING: Prospective controlled study in a
      university hospital department of anaesthesiology. PATIENTS: 60 patients with
      coronary artery bypass surgery, 300 paired measurements of S(v)O(2) and
      S(cv)O(2). MEASUREMENTS AND RESULTS: S(cv)O(2) and S(v)O(2) were analysed after
      induction of anaesthesia 15 min after cardiopulmonary bypass and 1, 6 and 18 h
      after admission to the intensive care unit. Regression analysis for the pooled
      measurements of S(cv)O(2) and S(v)O(2) showed a correlation R (2) = 0.52. After
      induction of anaesthesia 15 min after weaning from cardiopulmonary bypass and 6 h
      after admission to the intensive care unit the correlation coefficient was R (2)
      = 0.46, on admission to the intensive care unit it was R (2) = 0.42, and at 18 h
      it was R (2) = 0.38. Bland-Altman analysis for the measurements of S(cv)O(2) and
      S(v)O(2) showed a mean bias and LOA of 0.3% and -11.9 to +12.4%. In patients with
      a low S(cv)O(2) there was a trend to overestimate the S(v)O(2) by using the
      S(cv)O(2). The only factor that influenced the DeltaS(v)O(2) - S(cv)O(2) was the
      oxygen extraction rate (R (2) = 0.16). In patients with S(cv)O(2) below 70% this
      association was more pronounced (R (2) = 0.60). CONCLUSIONS: Our findings
      demonstrate that oxygen extraction rate is the major factor in the difference
      between S(v)O(2) and S(cv)O(2). Under certain circumstances S(cv)O(2) differed
      substantially from S(v)O(2). Therefore in selected patients both parameters
      should be monitored to exclude general or focal hypoperfusion.

PMID- 17525844
TI  - Correlation between alveolar recruitment/derecruitment and inflection points on
      the pressure-volume curve.
AB  - OBJECTIVE: To determine whether individual alveolar recruitment/derecruitment
      (R/D) is correlated with the lower and upper inflections points on the inflation
      and deflation limb of the whole-lung pressure-volume (P-V) curve. DESIGN AND
      SETTING: Prospective experimental study in an animal research laboratory.
      SUBJECTS: Five anesthetized rats subjected to saline-lavage lung injury.
      INTERVENTIONS: Subpleural alveoli were filmed continuously using an in vivo
      microscope during the generation of a whole-lung P-V curve using the super
      syringe technique. Alveolar R/D was correlated to the calculated inflection
      points on both limbs of the P-V curve. MEASUREMENTS AND RESULTS: There was
      continual alveolar recruitment along the entire inflation limb in all animals.
      There was some correlation (R2=0.898) between the pressure below which
      microscopic derecruitment was observed and the upper inflection point on the
      deflation limb. No correlation was observed between this pressure and the lower
      inflection point on the inflation limb. CONCLUSIONS: In this physiological
      experiment in lungs with pure surfactant deactivation we found that individual
      alveolar recruitment measured by direct visualization was not correlated with the
      lower inflection point on inflation whereas alveolar derecruitment was correlated
      with alveolar derecruitment on deflation. These data suggest that inflection
      points on the P-V curve do not always represent a change in alveolar number.

PMID- 17525842
TI  - Alveolar fluid clearance in acute lung injury: what have we learned from animal
      models and clinical studies?
AB  - BACKGROUND: Acute lung injury and the acute respiratory distress syndrome
      continue to be significant causes of morbidity and mortality in the intensive
      care setting. The failure of patients to resolve the alveolar edema associated
      with these conditions is a major contributing factor to mortality; hence there is
      continued interest to understand the mechanisms of alveolar edema fluid
      clearance. DISCUSSION: The accompanying review by Vadasz et al. details our
      current understanding of the signaling mechanisms and cellular processes that
      facilitate clearance of edema fluid from the alveolar compartment, and how these
      signaling processes may be exploited in the development of novel therapeutic
      strategies. To complement that report this review focuses on how intact organ and
      animal models and clinical studies have facilitated our understanding of alveolar
      edema fluid clearance in acute lung injury and acute respiratory distress
      syndrome. Furthermore, it considers how what we have learned from these animal
      and organ models and clinical studies has suggested novel therapeutic avenues to
      pursue.

PMID- 17525845
TI  - Vasodilator effect of nicorandil on retinal blood vessels in rats.
AB  - We examined the effect of nicorandil on retinal blood vessels in rats in vivo.
      Male Wistar rats (8 to 10 weeks old) were anaesthetised with thiobutabarbital
      (120 mg/kg, intraperitoneal). Fundus images were captured with a digital camera
      that was equipped with a special objective lens. Diameters of retinal blood
      vessels were measured with a personal computer. Nicorandil (1-300 microg kg(-1)
      min(-1), intravenous [i.v.]) increased diameters of retinal blood vessels and
      decreased systemic blood pressure in a dose-dependent manner. Both responses to
      nicorandil were attenuated by glibenclamide (20 mg/kg, i.v.), an adenosine
      triphosphate (ATP)-dependent K(+) (K(ATP)) channel blocker. On the other hand,
      indomethacin (5 mg/kg, i.v.), a cyclooxygenase inhibitor, attenuated the
      vasodilation of retinal blood vessels, but not depressor response, to nicorandil
      and sodium nitroprusside. Pinacidil (1-300 microg kg(-1) min(-1), i.v.), a K(ATP)
      channel opener, also dilated retinal blood vessels and decreased systemic blood
      pressure. The responses to pinacidil were prevented by glibenclamide, but not by
      indomethacin. The vasodilation of retinal arteriole, but not depressor response,
      to sodium nitroprusside (1-30 microg kg(-1) min(-1), i.v.), a nitric oxide donor,
      was attenuated by indomethacin. These results suggest that nicorandil dilates
      retinal blood vessels through opening of K(ATP) channels and production of
      prostaglandins that are probably generated by nitric oxide.

PMID- 17525846
TI  - Oesophageal perforation as a complication of primary pulmonary tuberculous
      lymphadenopathy in children.
AB  - BACKGROUND: Involvement of the oesophagus by tuberculosis is rare, and erosion
      and perforation of the oesophagus by tuberculous lymphadenopathy is an unusual
      complication of primary pulmonary tuberculosis. There are very few reports
      describing both CT and contrast swallow appearances of these lesions. OBJECTIVE:
      To describe the CT and contrast swallow appearances of oesophageal erosion and
      perforation by lymphadenopathy as a complication of primary pulmonary
      tuberculosis in children. MATERIALS AND METHODS: Imaging of three children with
      confirmed pulmonary tuberculosis and oesophageal perforation was retrospectively
      reviewed. RESULTS: Tuberculosis was confirmed by culture in all three patients.
      Contrast swallow demonstrated a contained leak in two patients and a tracheo
      oesophageal fistula in one. Two patients had mediastinal air and one patient had
      a mediastinal collection on CT. All patients had features diagnostic of pulmonary
      tuberculosis on CT. CONCLUSION: The imaging features comprise leakage of contrast
      medium with or without fistula formation on contrast swallow, large low-density
      lymph nodes on CT, and mediastinal air. The use of retrievable stents is a
      promising idea in this condition.

PMID- 17525847
TI  - Multi-modality imaging on track.

PMID- 17525848
TI  - Type of renal calculi: variation with age and sex.
AB  - The aim of this paper is to study the variations in the percentage of the
      different types of renal stones with age and sex. Renal calculi were classified
      according to their composition and structure. Stone formers were divided
      according to age and sex, and the percentage of each kind of calculi in the
      different considered age periods for men and women were determined. It was found
      that calcium oxalate dihydrate calculi decreased with age, but only in men. These
      calculi were also clearly predominant in men. Hydroxyapatite calculi decreased
      with age in both men and women, but they were predominant in women. Uric acid
      calculi increased with age in both men and women, but were predominant in men.
      Finally, it was found that calcium oxalate monohydrate unattached calculi
      increased with age in both men and women. As a main novelty, the study here
      presented demonstrates the importance of distinguishing between calcium oxalate
      monohydrate papillary stones and calcium oxalate monohydrate unattached stones,
      since the etiologic factors responsible for their origin must be clearly
      different.

PMID- 17525849
TI  - The rationale for radical cystectomy as primary therapy for T4 bladder cancer.
AB  - Treatment of T4 bladder cancer patients remains a clinical challenge.
      Conservative management is often insufficient regarding local control,
      neoadjuvant chemotherapy delays definite treatment while leading to increased
      therapy-associated morbidity and mortality during the course of the disease.
      Primary cystectomy has also been reported to be associated with a high
      complication rate and unsatisfactory clinical efficacy. Herein, we report
      postoperative outcome, including therapy-related complications, in 20 T4 bladder
      cancer patients subjected to primary cystectomy. Twenty patients underwent
      radical cystectomy for T4 bladder cancer. At the time of surgery, 8 patients had
      regional lymph node metastases. The median postoperative follow-up was 13 months
      for the whole group. Mean duration of postoperative hospitalization was 19 days.
      Ten patients received no intra- or postoperative blood transfusions, whereas an
      average number of 3 blood units were administered in the remaining cases. Major
      therapy-associated complications were paresthesia affecting the lower extremities
      (n = 3) as well as insignificant pulmonary embolism, enterocutaneous fistulation
      and acute renal failure in one patient, respectively. At the time of data
      evaluation, 11 patients were still alive after a follow-up of 20 months. Four
      patients >or=70 years at the time of cystectomy were still alive after 11, 22 and
      31 months following surgery, respectively. The current data demonstrate primary
      cystectomy for T4 bladder cancer as a technically feasible approach that is
      associated with a tolerable therapy-related morbidity. Additionally, satisfying
      clinical outcome is observed even in a substantial number of elderly patients.

PMID- 17525850
TI  - [Recurrence rates after pterygium excision with sliding conjunctival flap versus
      free conjunctival autograft].
AB  - BACKGROUND: After simple excision without additional surgical measures,
      pterygiums demonstrate high recurrence rates. According to the literature,
      recurrences may occur in up to 83% after simple excision compared to 5-21% after
      excision combined with conjunctival autografts. An alternative to the free
      conjunctival graft is the sliding conjunctival graft. METHODS: The data of 50
      patients operated over a period of 8 years were evaluated retrospectively. The
      long-term results after pterygium excision with free conjunctival graft vs
      sliding conjunctival flap were compared with data extracted from the literature.
      RESULTS: The average follow-up was 23 months. During this period, 18.5% of 27
      operated eyes with free conjunctival grafts developed a recurrence of pterygium.
      After excision with sliding conjunctival grafts only 6.9% of 29 operated and
      examined eyes developed recurrences. CONCLUSION: In the present study pterygium
      excision combined with sliding conjunctival graft was a simplified surgical
      technique with a lower recurrence rate compared to the free conjunctival graft.

PMID- 17525851
TI  - [Genetic and clinical heterogeneity in LCA patients. The end of uniformity].
AB  - BACKGROUND: Leber congenital amaurosis (LCA) usually describes patients with
      severely reduced vision due to a retinal dystrophy in early childhood. METHODS:
      In 135 families in a case series with severely reduced vision due to a retinal
      dystrophy in early childhood a complete ophthalmologic examination was extended
      by two-color threshold perimetry, fundus autofluorescence (FAF), und optical
      coherence tomography (OCT). Mutation screening included AIPL1, CRB1, CRX, GUCY2D,
      LRAT, RPE65, RPGRIP, and TULP1. RESULTS: GUCY2D mutations caused the most severe
      phenotype with severely reduced vision from birth but unremarkable fundus
      appearance. RPE65 mutations were correlated with an obvious lack of FAF. CRB1
      mutations showed a significantly thickened retina on OCT. CRX mutations were
      associated with a progressive form of cone-rod dystrophy. CONCLUSION: A genotype
      phenotype correlation for selected genes allows an optimized strategy for the
      molecular genetic work-up.

PMID- 17525852
TI  - [A gene defect in the promoter of the endothelial NO synthase as a risk factor
      for rheumatoid arthritis].
AB  - The risk to develop rheumatoid arthritis (RA) includes environmental as well as
      genetic factors. Moreover, RA, being an inflammatory disease, is itself
      considered to be a risk factor for coronary artery disease, as it - or its
      treatment - may lead to endothelial dysfunction. Likewise, a single nucleotide
      polymorphism in the promoter of the endothelial NO synthase ((-786)C/T) leads to
      endothelial dysfunction in (-786)CC homozygous individuals. This genetic defect
      occurs in significantly higher frequencies in patients with RA, and therefore
      must be regarded as a genetic risk factor for RA.

PMID- 17525853
TI  - Coupling of c-fos expression in the spinal cord and amygdala induced by dorsal
      neck muscles fatigue.
AB  - c-fos gene expression in the cervical spinal cord and amygdala was examined in
      anaesthetized rats following muscle fatigue caused by intermittent high-rate (100
      s(-1)) electrical stimulation of the dorsal neck muscles (m. trapezius and m.
      splenius). Fatigue-related increases in c-fos expression were observed on the
      stimulated muscle side in the cervical C2-C4 (layers 1, 3-5, 7 and 10) spinal
      segments, bilaterally in the lumbar L4-L6 (layer 1) segments and in contralateral
      central (Ce), medial (Me), and basomedial (BM) amygdaloid nuclei. A scarce number
      of staining cells were found within lateral and basolateral nuclei. The rostro
      caudal extent of c-fos expression in the spinal cord supports functional coupling
      of the cervical and lumbar regions during the neck muscle fatigue development.
      The distinct c-fos expression in the Ce and Me amygdaloid nuclei suggests that
      they may contribute to mediating the neck muscle fatigue-related nociception,
      autonomic and behavioural responses.

PMID- 17525855
TI  - Cloud observations for the statistical evaluation of the UV index at Toowoomba,
      Australia.
AB  - The development of a unique statistical model for the estimation of the UV index
      for all sky conditions with solar zenith angles of 60 degrees or less is
      reported. The model was developed based on available data from an integrated
      whole-sky automated sky camera and UV spectral irradiance measurement system that
      was collected every 5 min when the equipment was operational over a period of 1
      year. The final model does not include terms directly associated with solar
      radiation, but rather employs terms, and interactions between these terms,
      including the parameters of sky cover, solar obstruction, and cloud brightness.
      The correlation between the estimations of the model and the measured values was
      0.81. The developed model was evaluated on a data set spanning 5 months that had
      not been employed in the development of the model. The correlation for this new
      data set was 0.50, which increased to 0.65 for the cases when the clouds were
      considered to be a contributor to UV enhancement above that of a cloud-free day.

PMID- 17525854
TI  - The impact of IgG antibodies to recombinant Plasmodium falciparum 732var CIDR
      1alpha domain in mothers and their newborn babies.
AB  - Different domains of a novel full-length var gene (termed 732var) isolated from a
      placenta of a malaria-infected woman were expressed in Escherichia coli as
      recombinant proteins and analysed biochemically and immunologically. Two of
      these, the Duffy binding-like (DBL)-3gamma domain and the cysteine-rich
      interdomain region (CIDR)-1alpha were able to bind chondroitin sulfate A and
      CD36, respectively. The DBL-3gamma domain was investigated in a previous study
      and confirmed here to exhibit anti-disease characteristics related to pregnancy
      associated malaria. Mothers with high anti-DBL-3gamma antibody levels were
      protected from placental infection. The novel finding in this study is that
      babies born to mothers carrying anti-CIDR-1alpha antibodies had a delayed time to
      the first infection.

PMID- 17525856
TI  - Cardiovascular and lifestyle risk factors in lumbar radicular pain or clinically
      defined sciatica: a systematic review.
AB  - Lumbar radicular pain is a fairly common health problem, yet its risk factors are
      far from clear. There are no published systematic reviews on associations between
      cardiovascular or lifestyle risk factors and lumbar radicular pain or sciatica.
      The aim of this systematic literature review was to assess associations between
      these risk factors and lumbar radicular pain or sciatica. We conducted a
      systematic search of the Medline database for all original articles on lumbar
      radicular pain or sciatica published until August 2006. Twenty-two papers from 19
      studies were included in the review. Overweight or obesity was associated with
      sciatica in most of the case-control and cohort studies. Some studies showed an
      increased risk of lumbar radicular pain in smokers with a long smoking history or
      in those with high levels of physical activity. A few case-control studies showed
      an association between serum C-reactive protein and sciatica. No consistent
      associations were found for serum lipids levels or high blood pressure. In
      summary, the associations of overweight, long smoking history, high physical
      activity and a high serum C-reactive protein level with lumbar radicular pain or
      sciatica were substantiated by the present review. However, more prospective
      studies are needed in order to further clarify these associations and the
      mechanisms of action.

PMID- 17525857
TI  - Candidemia in immunocompromised and immunocompetent critically ill patients: a
      prospective comparative study.
AB  - The purpose of this study was to compare the risk factors, clinical
      manifestations, and outcome of candidemia in immunocompromised (IC) and
      nonimmunocompromised (NIC) critically ill patients. Data were collected
      prospectively over a 2-year period (02/2000-01/2002) from patients in a 25-bed,
      medical-surgical intensive care unit (ICU). Eligible for participation in this
      study were patients who developed candidemia during their ICU stay. Patients
      under antifungal therapy and with a confirmed systemic fungal infection prior to
      the diagnosis of candidemia were excluded. Cultures of blood, urine, and stool
      were performed for all patients in the study, and all patients underwent
      endoscopy/biopsy of the esophagus for detection of Candida. Smears and/or
      scrapings of oropharyngeal and esophageal lesions were examined for hyphae and/or
      pseudohyphae and were also cultured for yeasts. During the study period, 1,627
      patients were hospitalized in the ICU, 57% for primary medical reasons and 43%
      for surgical reasons. After application of the study's inclusion and exclusion
      criteria, 24 patients with candidemia (9 IC and 15 NIC) were analyzed. Total
      parenteral nutrition was more common in IC than in NIC patients (9/9 [100%] vs
      8/15 [53%], p = 0.02). Oropharyngeal candidiasis was detected in 5 of 9 (55.5%)
      IC patients and in 1 of 15 (6.5%) NIC patients (p = 0.015). Esophageal
      candidiasis was also more common in IC than in NIC patients (4/9 [44%] vs 0/15
      [0%], p = 0.012). Among the 9 IC patients, all except 2 died, resulting in a
      crude mortality of 78%; among the 15 NIC patients, 9 died, resulting in a crude
      mortality of 60% (p > 0.05). Autopsy was performed in two IC and in six NIC
      patients, with disseminated candidiasis found in one IC patient. Oropharyngeal
      and esophageal candidiasis are frequent in IC patients with candidemia. In
      contrast, this coexistence is rare in NIC critically ill patients with Candida
      bloodstream infections. A high mortality was noted in both IC and NIC critically
      ill patients with candidemia.

PMID- 17525859
TI  - Colorectal carcinoma: a retrospective, descriptive study of age, gender, subsite,
      stage, and differentiation in Iran from 1995 to 2001 as observed in Tehran
      University.
AB  - PURPOSE: Colorectal carcinoma is one of the most common cancers in the world as
      well as in Iran. There are differences in subsite of the carcinoma when
      considering age and gender. This study was designed to describe the distribution
      of colorectal carcinoma by age at diagnosis, gender, and subsite of the tumor.
      These factors also are evaluated in conjunction with disease stage and tumor
      differentiation at the time of diagnosis. METHODS: Data from 419 patients from a
      population that receives no screening between April 1995 and March 2001 operated
      on in the Cancer Institute and Imam Khomieni Hospital with a diagnosis of
      colorectal cancer were used to describe distribution of the colorectal carcinoma
      by age, gender, tumor subsite and pathology, and stage at diagnosis. RESULTS:
      There were 403 (96.2 percent) cases of adenocarcinoma. Males and females
      constituted 52.4 and 47.6 percent of cases, respectively. The mean age was 52.3
      years. Patients were divided into two age groups (40 years and younger, and older
      than 40 years); 16.4 percent of patients had tumors in the proximal colon and
      83.6 percent in distal parts. Most patients were Stage II and III (48.1 and 33.4
      percent, respectively). Tumor subsite distribution was almost the same between
      the two age groups (aged 40 years and younger: proximal, 18.5 percent, and
      distal, 81.5 percent; older than aged 40 years: proximal, 15.7 percent, and
      distal, 84.3 percent). Most patients in the younger age group were Stage III (45
      percent) and in the older age group were Stage II (53.2 percent; P<0.001). Tumor
      differentiation proportions in patients aged 40 years and younger were: good,
      24.4 percent; moderate, 53.6 percent; poor, 22 percent; and in patients older
      than aged 40 years were: good, 41.5 percent; moderate, 52.6 percent; poor, 5.9
      percent (P<0.001). There were no differences in stage and tumor differentiation
      between two genders, but most of the patients with tumors in proximal colon were
      males (62.5 percent; P=0.1). CONCLUSIONS: Most of the colorectal carcinomas were
      in distal parts in our study, so most of these carcinomas can be detected by
      proctosigmoidoscopy. Because younger patients had more advanced disease, the
      importance of screening and "clinical suspicion" in the young is important.

PMID- 17525861
TI  - A diverting stoma is not necessary when performing a handsewn coloanal
      anastomosis for lower rectal cancer.
AB  - PURPOSE: Although a temporary diverting stoma is a frequent surgical procedure
      for the protection of anastomosis in a sphincter-preserving operation for lower
      rectal cancer, its impact on anastomotic leakage is not conclusive. This study
      was designed to evaluate anastomotic complications after ultralow anterior
      resection and handsewn coloanal anastomosis without a diverting stoma for lower
      rectal cancer patients. METHODS: Between January 1995 and December 2005, 96
      patients were treated by ultralow anterior resection and handsewn coloanal
      anastomosis for lower rectal cancer. Fifty-one patients received preoperative
      concurrent chemoradiation, whereas 45 had no preoperative treatment. No diverting
      stoma was created in any of these cases. The anastomotic complications were
      evaluated between the groups. RESULTS: Six of 96 patients (6.1 percent) developed
      anastomotic complications: three anastomotic stenoses, one partial anastomotic
      dehiscence, one retrorectal abscess, and one rectovaginal fistula. All of the
      complications occurred in the preoperative radiation group, whereas none from the
      nonradiation group had an anastomotic complication (P=0.017). The patients with
      stenosis and partial dehiscence were managed conservatively. The patient with
      retrorectal abscess was treated with debridement, irrigation and drainage, and
      seton procedure with a transanal approach. The patient with rectovaginal fistula
      underwent a second coloanal anastomosis. CONCLUSIONS: The anastomotic
      complication rate was low even without a diverting stoma. This study suggests
      that a diverting stoma is not necessary when performing a handsewn coloanal
      anastomosis for lower rectal cancer however, an effort should be made for healthy
      anastomotic healing in patients with rectal cancer who are preoperatively
      radiated.

PMID- 17525860
TI  - The impact of preoperative immunomodulation on pouch-related septic complications
      after ileal pouch-anal anastomosis.
AB  - PURPOSE: We studied preoperative and perioperative factors with particular
      attention to the role of immunomodulatory medication, which may impact the
      incidence of pouch-related septic complications. METHODS: A retrospective review
      of data from patients who underwent ileal pouch surgery during a 20-year period
      from 1985 to 2005 was performed. Preoperative use of immunomodulatory medication
      along with perioperative clinical, surgical, and disease variables were recorded.
      Patients were monitored for pouch-related sepsis in the early (within 30 days of
      surgery) and late (after 30 days of surgery) postoperative periods. Univariate
      and multivariate logistic regression analysis was performed. RESULTS: There were
      445 patients (206 females; 46.4 percent). Median age was 36 (interquartile range,
      27-46) years. Median follow-up period was 52 (interquartile range, 26-86) months.
      Complete data were available for 335 patients. Early sepsis was seen in 58
      patients (17.3 percent). Another 22 patients (6.5 percent) developed late sepsis.
      On multivariate analysis, only steroid use remained predictive of higher rates of
      early sepsis (odds ratio, 1.81; 95 percent confidence interval, 1.02-3.45;
      P=0.002). Likewise on multivariate analysis, both male gender (odds ratio, 0.24;
      95 percent confidence interval, 0.09-0.71; P=0.007) and 5-aminosalicylic-acid use
      (odds ratio, 0.22; 95 percent confidence interval, 0.08-0.76; P=0.023) remained
      predictive of lower rates of sepsis. CONCLUSIONS: Preoperative steroid use is
      associated with higher rates of early but not late pouch-related septic
      complications. We recommend that patients be weaned of steroids before ileal
      pouch surgery or be warned of the higher risk of postoperative sepsis.

PMID- 17525862
TI  - NAT2 fast acetylator genotype is associated with an increased risk of colorectal
      cancer in Taiwan.
AB  - In Taiwan, colorectal cancer has one of the highest rates of increased incidence
      in the past two decades. Heterocyclic amines from dietary cooked meats are
      metabolically activated by NAT2 (N-acetyltransferase 2), which are associated
      with colorectal cancer incidence. Thus, the NAT2 fast acetylator genotype may be
      associated with colorectal cancer risk. However, the association between the NAT2
      genotype and colorectal cancer risk is not clearly understood. We conducted a
      study with 244 primary colorectal cancer cases and 299 cancer-free healthy
      control subjects to verify the association of NAT2 polymorphisms with the risk of
      Taiwanese colorectal cancer. Our data showed that subjects with the NAT2 W/W
      homozygous genotype had a 1.63-fold increased risk of colorectal cancer compared
      with those with the Mx/Mx slow acetylator genotype (95 percent confidence
      interval, 1.03-2.58); however, no risk was found in the W/Mx heterozygous and
      Mx/W+W/W fast acetylator genotypes. Being stratified by gender factors, the
      colorectal cancer risk in females with homozygous W/W or Mx/W+W/W fast
      acetylators increased 2.47-fold and 2.13-fold compared with those with the Mx/Mx
      slow acetylator genotype (95 percent confidence interval, 1.27-4.82 for W/W
      genotype; 95 percent confidence interval, 1.17-3.89 for Mx/W+W/W genotype);
      however, the risk of the NAT2 genotype and colorectal cancer was not observed in
      males. Collectively, patients with the NAT2 fast acetylator genotype were more
      prone to colorectal cancer and reflected the possibility that exposure to
      heterocyclic amines may contribute to colorectal cancer development in Taiwan,
      especially in Taiwanese females.

PMID- 17525863
TI  - MRSA-related perianal abscesses: an underrecognized disease entity.
AB  - PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) in perianal abscesses
      represents an underrecognized condition. It is unclear whether these abscesses
      differ in presentation or other characteristics from their non-MRSA counterparts.
      METHODS: Patients diagnosed with perianal abscess, who underwent incision and
      drainage between January 2003 and September 2005, were identified
      retrospectively. Demographics, abscess characteristics (induration, erythema,
      abscess size, amount of purulence), presence of MRSA on culture, MRSA
      susceptibilities, and clinical course were collected. RESULTS: A total of 104
      patients (62.5 percent male; mean age, 42.7+/-13.7 years) were treated for
      perianal abscess. For the 69 patients cultured at drainage, MRSA was present in
      34.8 percent (24/69) of cases (95 percent confidence interval, 24.6-46.6
      percent). MRSA-positive patients did not significantly differ from MRSA-negative
      patients with respect to age, MRSA risk factors, duration of symptoms, white
      blood cell count at admission, or length of stay. Patients were more likely to be
      MRSA-positive if they possessed extensive induration (odds ratio, 6.52; P=0.003),
      extensive erythema (odds ratio, 5.75; P=0.003), or small amount of purulence
      (odds ratio, 9.72; P=0.006). Ischiorectal abscesses were significantly less
      likely to be MRSA-positive (odds ratio, 0.34; P=0.016). No patients with MRSA
      positive abscesses developed fistulas. All MRSA isolates were resistant to beta
      lactam antibiotics and had limited susceptibility to quinolones. CONCLUSIONS: The
      prevalence of MRSA in perianal abscesses has not been described previously and is
      higher in our group of patients than would be expected. MRSA-positive patients
      cannot be identified by risk factors alone. Antibiotic resistance spectra of MRSA
      vary from that of enteric bacteria typically seen in perianal abscesses.
      Therefore, it may be beneficial to culture all perianal abscesses with extensive
      induration and erythema or minimal purulence.

PMID- 17525864
TI  - Biotechnological production of gluconic acid: future implications.
AB  - Gluconic acid (GA) is a multifunctional carbonic acid regarded as a bulk chemical
      in the food, feed, beverage, textile, pharmaceutical, and construction
      industries. The favored production process is submerged fermentation by
      Aspergillus niger utilizing glucose as a major carbohydrate source, which
      accompanied product yield of 98%. However, use of GA and its derivatives is
      currently restricted because of high prices: about US$ 1.20-8.50/kg. Advancements
      in biotechnology such as screening of microorganisms, immobilization techniques,
      and modifications in fermentation process for continuous fermentation, including
      genetic engineering programmes, could lead to cost-effective production of GA.
      Among alternative carbohydrate sources, sugarcane molasses, grape must show
      highest GA yield of 95.8%, and banana must may assist reducing the overall cost
      of GA production. These methodologies would open new markets and increase
      applications of GA.

PMID- 17525866
TI  - Topographic association of angioscopic yellow plaques with coronary
      atherosclerotic plaque: assessment with quantitative colorimetry in human
      coronary artery autopsy specimens.
AB  - Yellow plaques seen during coronary angioscopy are thought to be the surrogates
      for superficial intimal lipids in coronary plaque. Given diffuse and
      heterogeneous nature of atherosclerosis, yellow plaques in coronaries may be seen
      as several yellow spots on diffuse coronary plaque. We examined the topographic
      association of yellow plaques with coronary plaque. In 40 non-severely stenotic
      ex-vivo coronary segments (average length: 52.2 +/- 3.1 mm), yellow plaques were
      examined by angioscopy with quantitative colorimetry. The segments were cut
      perpendicular to the long axis of the vessel at 2 mm intervals, and 1045 slides
      with 5 microm thick tissue for whole segments were prepared. To construct the
      plaque surface, each tissue slice was considered to be representative of the
      adjacent 2 mm. The circumference of the lumen and the lumen border of plaque were
      measured in each slide, and the plaque surface region was constructed. Coronary
      plaque was in 37 (93%) of 40 segments, and consisted of a single mass [39.9 +/-
      3.9 (0-100) mm, 311.3 +/- 47.4 (0.0-1336.2) mm2]. In 30 (75%) segments, multiple
      (2-9) yellow plaques were detected on a mass of coronary plaque. The number of
      yellow plaques correlated positively with coronary plaque surface area (r = 0.77,
      P < 0.0001). Yellow plaques in coronaries detected by angioscopy with
      quantitative colorimetry, some of them are associated with lipid cores underneath
      thin fibrous caps, may be used to assess the extent of coronary plaque. Further
      research using angioscopy could be of value to study the association of high-risk
      coronaries with acute coronary syndromes.

PMID- 17525865
TI  - Functional MRI of language in aphasia: a review of the literature and the
      methodological challenges.
AB  - Animal analogue studies show that damaged adult brains reorganize to accommodate
      compromised functions. In the human arena, functional magnetic resonance imaging
      (fMRI) and other functional neuroimaging techniques have been used to study
      reorganization of language substrates in aphasia. The resulting controversy
      regarding whether the right or the left hemisphere supports language recovery and
      treatment progress must be reframed. A more appropriate question is when left
      hemisphere mechanisms and when right-hemisphere mechanisms support recovery of
      language functions. Small lesions generally lead to good recoveries supported by
      left-hemisphere mechanisms. However, when too much language eloquent cortex is
      damaged, right-hemisphere structures may provide the better substrate for
      recovery of language. Some studies suggest that recovery is particularly
      supported by homologues of damaged left-hemisphere structures. Evidence also
      suggests that under some circumstances, activity in both the left and right
      hemispheres can interfere with recovery of function. Further research will be
      needed to address these issues. However, daunting methodological problems must be
      managed to maximize the yield of future fMRI research in aphasia, especially in
      the area of language production. In this review, we cover six challenges for
      imaging language functions in aphasia with fMRI, with an emphasis on language
      production: (1) selection of a baseline task, (2) structure of language
      production trials, (3) mitigation of motion-related artifacts, (4) the use of
      stimulus onset versus response onset in fMRI analyses, (5) use of trials with
      correct responses and errors in analyses, and (6) reliability and stability of
      fMRI images across sessions. However, this list of methodological challenges is
      not exhaustive. Once methodology is advanced, knowledge from conceptually driven
      fMRI studies can be used to develop theoretically driven, mechanism-based
      treatments that will result in more effective therapy and to identify the best
      patient candidates for specific treatments. While the promise of fMRI in the
      study of aphasia is great, there is much work to be done before this technique
      will be a useful clinical tool.

PMID- 17525867
TI  - Expression of EGFP-spider dragline silk fusion protein in BmN cells and larvae of
      silkworm showed the solubility is primary limit for dragline proteins yield.
AB  - Spider dragline silk is a unique fibrous protein with combination of tensile
      strength and elasticity, but the isolation of large amount of silk from spiders
      is not feasible. In this paper, we used a newly established Bac-to-Bac/BmNPV
      Baculovirus expression system to express the recombinant spider (Nephila clavata)
      dragline silk protein (MaSp1) fused EGFP in BmN cells and larvae of silkworm. A
      70 kDa fusion protein was visualized after rBacmid/BmNPV/drag infection by SDS
      PAGE and immunoblotting analysis. Fusion protein expressed in the BmN cells
      probably occupied five percent of the cell total protein; In a silkworm larva,
      approximately 6 mg fusion proteins were expressed. Solubility analysis of the
      expressed spider dragline silk protein indicated that 60% fusion protein is
      insoluble. EGFP fluorescence showed that fusion protein is tend to form aggregate
      by self assemblage. The results indicated the solubility is the primary limit for
      spider dragline proteins yield. It also suggested that directly produce fibrous
      spider silk in the secreting-silk organs of the transgenic silkworm larvae might
      be a better method.

PMID- 17525869
TI  - Mitotic control of dTTP pool: a necessity or coincidence?
AB  - The fidelity of DNA replication in eukaryotic cells requires a balanced dNTP
      supply in the S phase. During the cell cycle progression, the production of dTTP
      is highly regulated to coordinate with DNA replication. Intracellular thymidine
      is salvaged to dTTP by cytosolic thymidine kinase (TK1) and thymidylate kinase
      (TMPK), both of which expression increase in the G1/S transition and diminish in
      the mitotic phase via proteolytic destruction. Anaphase promoting
      complex/cyclosome (APC/C)-mediated ubiquitination targets TK1 and TMPK to undergo
      proteasomal degradation in mitosis, by which dTTP pool is minimized in the early
      G1 phase of the next cell cycle. In this review, we will focus on regulation of
      TK1 in the post-S phase and the importance of mitotic proteolysis in controlling
      dNTP balance, replication stress and genomic stability. Finally, we discuss how
      thymidine pool and oligomeric forms of TK1 can affect mitotic control of dTTP.

PMID- 17525870
TI  - Fast tracking in liver transplantation. Immediate postoperative tracheal
      extubation: feasibility and clinical impact.
AB  - Increased survival rates after orthotopic liver transplantation (OLT) in patients
      with end-stage liver disease have become possible due to an advanced
      understanding of the pathophysiology of liver disease, the establishment of
      multiorgan procurement and preservation techniques, and the development of safer
      and more potent immunosuppressive drugs. In addition, standardisation of surgical
      techniques and advances in anaesthetic management have contributed significantly
      to this development. The up-to-date concept of improving patient outcome
      following OLT includes a fast track approach in selected patient populations,
      which may shorten ICU and/or hospital stay and reduce costs. In particular,
      immediate postoperative extubation has been identified as an excellent tool to
      achieve both improved clinical results and a reduced drain on financial
      resources. Studies on fast tracking protocols have shown clearly that prolonged
      mechanical ventilation following surgery is no longer justified in the majority
      of patients. On current evidence at least 70-80% of transplant recipients can be
      extubated immediately following surgery. The incidence of reintubation is not
      increased hereafter when compared to patients extubated later. However, special
      attention should be focused on liver transplant recipients in poor clinical
      condition at the time of OLT, undergoing complicated surgery, or receiving liver
      grafts with severe preservation injury. These patients might not be eligible for
      fast tracking protocols and may be at increased risk of prolonged postoperative
      mechanical ventilation.

PMID- 17525871
TI  - Sweat testing practice in Swiss hospitals.
AB  - AIMS: To determine whether the current practice of sweat testing in Swiss
      hospitals is consistent with the current international guidelines. METHODS: A
      questionnaire was mailed to all children's hospitals (n = 8), regional paediatric
      sections of general hospitals (n = 28), and all adult pulmonology centres (n = 8)
      in Switzerland which care for patients with cystic fibrosis (CF). The results
      were compared with published "guidelines 2000" of the American National Committee
      for Clinical Laboratory Standards (NCCLS) and the UK guidelines of 2003. RESULTS:
      The response rate was 89%. All 8 children's hospitals and 18 out of 23 answering
      paediatric sections performed sweat tests but none of the adult pulmonology
      centres. In total, 1560 sweat tests (range: 5-200 tests/centre/year, median 40)
      per year were done. 88% (23/26) were using Wescor systems, 73% (19/26) the
      Macroduct system for collecting sweat and 31% (8/26) the Nanoduct system. Sweat
      chloride was determined by only 62% (16/26) of all centres; of these, only 63%
      (10/16) indicated to use the recommended diagnostic chloride-CF-reference value
      of >60 mmol/l. Osmolality was measured in 35%, sodium in 42% and conductivity in
      62% of the hospitals. Sweat was collected for maximal 30-120 (median 55) minutes;
      only three centres used the maximal 30 minutes sample time recommended by the
      international guidelines. CONCLUSIONS: Sweat testing practice in Swiss hospitals
      was inconsistent and seldom followed the current international guidelines for
      sweat collection, analyzing method and reference values. Only 62% were used the
      chloride concentration as a diagnostic reference, the only accepted diagnostic
      measurement by the NCCLS or UK guidelines.

PMID- 17525872
TI  - Coronary artery disease screening in diabetic patients: how good is guideline
      adherence?
AB  - INTRODUCTION: Diabetic patients are at high risk for coronary artery disease
      (CAD), which is the leading cause of death in this population. The Swiss Society
      of Endocrinology-Diabetology (SSED) recommends CAD screening for diabetic
      patients with > or = 2 additional cardiovascular risk factors (CVRF), by stress
      echocardiography (SE) or myocardial perfusion imaging (MPI). The aim of this
      study was to assess the application of these guidelines and the treatment of CVRF
      in the diabetes outpatient clinics of the five Swiss University Hospitals.
      METHODS: The study was initiated in Lausanne and the study questionnaires were
      circulated to the endocrinologists of the five Swiss University Hospitals.
      Practitioners were asked to include consecutive patients attending the diabetes
      outpatient clinics over one month. Prevalence of CAD, screening methods for CAD,
      prevalence of CVRF, biological analyses over the last 6 months and medical
      therapy were recorded. RESULTS: A total of 302 subjects were included. The mean
      age was 53 +/- 14 years, 68% had type 2 diabetes, 27% type 1 and 5% other types.
      Among T2DM with > or = 2 CVRF, 45% were screened for CAD according to SSED
      guidelines. In T2DM 25% had blood pressure < or = 130/80 mm Hg, 15% a lipid
      profile within target, 23% HbA1c < or = 7.0%. Overall, 2% achieved all 3 targets.
      CONCLUSIONS: Only 45% of T2DM with > or = 2 CVRF were screened for CAD according
      to SSED guidelines and 2% of T2DM had proper control over all CVRF. Efforts are
      still necessary to improve CAD prevention and screening of diabetic patients in
      Swiss University Hospitals.

PMID- 17525873
TI  - Rehabilitation in acute stroke patients in German-speaking Switzerland.
AB  - PRINCIPLES: The aim of this study was to obtain an overview of stroke-specialised
      rehabilitation facilities in German-speaking Switzerland, as well as the numbers
      of stroke patients treated. It also focused on the mode of goal-setting and
      evaluation, and the use of instruments to assess the patient's state and
      progress. METHOD: Out of 28 stroke rehabilitation facilities, 21 participated in
      a structured telephone interview. Of these, 18 institutions provided full data.
      RESULTS: The results show that the facilities (n = 18) vary considerably in
      numbers of patients treated per year (O 124, range 7-500) and length of stay (O
      40 +/- 17.23). Goal-setting and evaluation, including the setting of short term
      and long term goals, is a common feature. They differ, however, in terms of
      patient involvement, processes and professions participating in goal-setting and
      evaluation. A variety of instruments are used for patient assessment at admission
      and during rehabilitation. Admission to rehabilitation does not rely on
      standardised patient health status assessment. CONCLUSIONS: Stroke rehabilitation
      in German-speaking Switzerland embraces a heterogeneous landscape with respect to
      use of instruments, goal-setting and evaluation process and patient involvement.
      To facilitate comparison, the same core instruments for assessment and evaluation
      should be selected and consistently applied. Also, the admission criterion
      "potential for rehabilitation" should be transformed into a universally and
      scientifically valid term. The effect of patient involvement in goal-setting on
      rehabilitation outcome has not yet been investigated. Thus no recommendations can
      be made for the moment.

PMID- 17525874
TI  - Adenosine-induced severe acute respiratory distress in chronic obstructive
      pulmonary disease: a myth?

PMID- 17525875
TI  - Ketamine and the potential role for rapid-acting antidepressant medications.

PMID- 17525876
TI  - Obstructive sleep apnea and cardiovascular disease - time to act!
AB  - Sleep related breathing disorders are common and their potential to disrupt sleep
      leading to daytime fatigue and hypersomnolence is widely acknowledged. In the
      future, obstructive sleep apnoea (OSA) may become even more important because
      obesity as a main risk factor is increasingly prevalent. Apart from disturbing
      sleep, OSA has also been recognised as a risk factor for hypertension, acute
      cardiovascular events and metabolic disturbance such as insulin resistance.
      Several randomised controlled trials demonstrated a positive effect of nasal
      continuous positive airway pressure (CPAP) treatment on arterial blood pressure,
      leading the "Joint National Council on High Blood Pressure" to list obstructive
      sleep apnoea as the first identifiable cause of arterial hypertension. Recently,
      a growing body of evidence demonstrated also a risk reduction of fatal and non
      fatal cardiovascular events by treatment of obstructive sleep apnoea. A
      beneficial effect of treatment of OSA was also shown for patients with heart
      failure, or heart rhythm disturbance. Obstructive sleep apnoea may no longer be
      seen as a cause for daytime sleepiness and impaired quality of life only, but
      also as an independent risk factor, at least for the occurrence of hypertension
      but probably for any cardiovascular and cerebrovascular disease. While
      prospective controlled trials to document a reduction of cardiovascular morbidity
      and mortality are awaited, therapeutic nihilism seems no longer appropriate. With
      effective treatment available, subgroups that may profit best remain to be
      identified.

PMID- 17525877
TI  - Acute pain in adults admitted to the emergency room: development and
      implementation of abbreviated guidelines.
AB  - AIM: Although acute pain is frequently reported by patients admitted to the
      emergency room, it is often insufficiently evaluated by physicians and is thus
      undertreated. With the aim of improving the care of adult patients with acute
      pain, we developed and implemented abbreviated clinical practice guidelines (CG)
      for the staff of nurses and physicians in our hospital's emergency room. METHODS:
      Our algorithm is based upon the practices described in the international
      literature and uses a simultaneous approach of treating acute pain in a rapid and
      efficacious manner along with diagnostic and therapeutic procedures. RESULTS:
      Pain was assessed using either a visual analogue scale (VAS) or a numerical
      rating scale (NRS) at ER admission and again during the hospital stay. Patients
      were treated with paracetamol and/or NSAID (VAS/NRS <4) or intravenous morphine
      (VAS/NRS > or =04). The algorithm also outlines a specific approach for patients
      with headaches to minimise the risks inherent to a non-specific treatment. In
      addition, our algorithm addresses the treatment of paroxysmal pain in patients
      with chronic pain as well as acute pain in drug addicts. It also outlines
      measures for pain prevention prior to minor diagnostic or therapeutic procedures.
      CONCLUSIONS: Based on published guidelines, an abbreviated clinical algorithm
      (AA) was developed and its simple format permitted a widespread implementation.
      In contrast to international guidelines, our algorithm favours giving nursing
      staff responsibility for decision making aspects of pain assessment and treatment
      in emergency room patients.

PMID- 17525878
TI  - Inappropriate interventions during the long-term follow-up of patients with an
      implantable defibrillator.
AB  - QUESTIONS UNDER STUDY: In patients with an implantable defibrillator (ICD),
      inappropriate ICD interventions alter the quality of life, may cause
      hospitalisations and limit cost-effectiveness. The aim of the study was to
      determine the incidence and causes of inappropriate ICD interventions, and to
      identify patients at risk. METHODS: For this observational longitudinal study,
      consecutive patients undergoing ICD implantation at the University Hospital of
      Berne were included in a registry. All stored electrograms of episodes triggering
      ICD interventions were systematically reviewed and analysed to determine whether
      ICD interventions were appropriate or inappropriate. Inappropriate ICD
      interventions were classified according to their cause, and risk factors were
      sought. RESULTS: 214 consecutive patients were followed during a median time of
      2.7 years (3.7 years IQR, 698 patient years). 81 inappropriate ICD interventions
      occurred in 58 patients (27%). Factors triggering inappropriate ICD interventions
      included atrial fibrillation and flutter (n = 35, 44%), sinus tachycardia (n =
      26, 32%), lead fracture (n = 12), recurrent self-terminating ventricular
      tachycardia (n = 5), double-counting due to T-wave oversensing (n = 3). The only
      identifiable risk factor for inappropriate ICD interventions was sustained
      ventricular tachycardia as index arrhythmia. CONCLUSIONS: An important proportion
      of ICD patients suffer inappropriate ICD interventions that are most commonly due
      to supraventricular arrhythmias. Patients with ventricular tachycardia prior to
      ICD implantation are at higher risk of inappropriate ICD interventions.
      Interventions aiming at decreasing the risk of inappropriate ICD interventions
      should be considered in these patients.

PMID- 17525879
TI  - Intravenous ketamine therapy in a patient with a treatment-resistant major
      depression.
AB  - BACKGROUND: Recently, reports from North America have indicated that the
      intravenous infusion of ketamine hydrochloride (an N-methyl-d-aspartate receptor
      antagonist) results in a sudden and robust improvement of depression symptoms.
      OBJECTIVE: To corroborate antidepressant effectiveness of IV ketamine in a
      patient with a co-occurring substance use disorder for the first time in a
      European clinical setting. DESIGN: Open label trial Methods: A 55-year-old male
      subject with a treatment-resistant major depression and a co-occurring alcohol
      and benzodiazepine dependence received an intravenous infusion of 0.5 mg/kg
      ketamine over a period of 50 minutes. Effects were assessed by means of a
      clinical interview, the 21-item Hamilton Depression Rating scale (HDRS), and the
      21-item Beck Depression Inventory (BDI) at baseline, 1 hour, 1 day, 2 days, and 7
      days after intervention. RESULTS: Following the administration of ketamine the
      subject experienced a significant improvement of his symptoms peaking on the 2nd
      day post infusion (HDRS from 36 to 16; -56.6%, BDI from 26 to 9; -65.4%). The
      subject first reported improvements 25 min. into the infusion and continued to
      describe positive effects throughout the subsequent 7 days. CONCLUSION: Ketamine
      not only seems to have strong antidepressant effects but also to act very
      swiftly. These actions were unaffected by an alcohol or benzodiazpine dependence.

PMID- 17525880
TI  - Blood lactate and heat stress during training in rowers.
AB  - The purpose of the present study was to test the hypothesis that large increases
      in blood lactate concentration ([La] (b)) and/or body temperature may occur
      during an endurance training on a rowing ergometer and disrupt training. The
      influence of an increase in air convection on the capacity to perform a prolonged
      exercise was also explored. Ten trained oarsmen were asked to undergo twice, in
      control (C) and increased air ventilation (AV) conditions, two 30-min trainings
      on a rowing ergometer at a work rate corresponding to 2.5 mmol . L (-1) of [La]
      (b) determined during a previous incremental exercise (P (2.5)). Four subjects
      did not complete the training session in C despite a steady state in [La] (b) in
      two of them. In these four subjects, the end of the exercise was associated with
      the highest measured rectal temperatures (T (re), 39.4 +/- 0.1 degrees C) and
      rate of perceived exertion (RPE, 17.8 +/- 0.3). Regarding the six other subjects,
      their heart rate, oxygen uptake, RPE, T (re) and water loss values were lower (p
      < 0.05) in AV than in C. [La] (b) displayed the same profile in C and AV. This
      study suggests that i) high body temperature may constitute a significant factor
      of perceived exertion and disrupt indoor training session, and ii) capacity to
      perform an endurance training on a rowing ergometer was improved by increasing
      air convection.

PMID- 17525881
TI  - Random motor unit activation by electrostimulation.
AB  - Whether the involvement of motor units is different between surface neuromuscular
      electrostimulation and voluntary activation remains an unresolved issue. The aim
      of this pilot study was to verify if motor unit activation during
      electrostimulation is nonselective/random (i.e., without obvious sequencing
      related to fibre type), as recently suggested by Gregory and Bickel [6]. Sixteen
      healthy men randomly performed submaximal isometric contractions (10-s duration)
      of the quadriceps femoris muscle at 20, 40 and 60 % of maximal voluntary torque
      under both stimulated and voluntary conditions. During the contractions, paired
      stimuli were delivered to the femoral nerve (twitch interpolation technique) and
      the characteristics of the superimposed doublet were compared between the two
      conditions. For each torque level, time-to-peak torque was significantly longer
      (p range = 0.05 - 0.0002) during electrostimulation compared to voluntary
      contractions. Moreover, time-to-peak torque during voluntary trials decreased
      significantly when increasing the torque level from 20 to 60 % of maximal
      voluntary torque (p range = 0.03 - 0.0001), whereas it was unchanged during
      electrostimulation. In conclusion, over-the-muscle electrostimulation would
      neither result in motor unit recruitment according to Henneman's size principle
      nor would it result in a reversal in voluntary recruitment order. During
      electrostimulation, muscle fibres are activated without obvious sequencing
      related to fibre type.

PMID- 17525882
TI  - The soluble leptin receptor of regular exercisers.
AB  - This study examined the concentrations and the relationships of soluble leptin
      receptor (sLR) and leptin levels among both physically active people and lean
      sedentary persons. Information collected for this study came from twelve joggers
      (JOG), ten weight trainers (WET) and eleven lean sedentary persons (CON). Regular
      exercisers were defined as those who consistently participated in jogging or
      weight training 30 minutes a day, at least four times a week, for a period of no
      less than three years prior to the study. The CON group was defined as
      exercising, at most, one time per week, less than 20 minutes each time if at all.
      Leptin and sLR were analyzed using enzyme-linked immunosorbent assay. The results
      show the BMI of the WET group to be higher than the other groups, yet their
      percent body fat was not significantly different. Although sLR levels of the JOG
      group were higher than the WET and CON groups, their free leptin index (FLI) did
      not show a significant difference. The sLR levels for joggers were higher than
      the weight trainers. The sLR concentration or the ratio of sLR to fat mass may be
      an alternative index to FLI for comparing physically active and lean people.

PMID- 17525883
TI  - Proteases in doping control analysis.
AB  - Urine manipulation in sports drug testing has become a serious problem for doping
      control laboratories, and recent scandals in elite endurance sports have revealed
      the problem of urine manipulation presumably using proteases, which will impede
      the detection of drugs such as erythropoietin (EPO) or other peptide hormones.
      Using commonly accepted analytical strategies, a protocol was developed enabling
      the determination of elevated protease activities in doping control specimens
      followed by the visualization of protein degradation and identification of
      proteases such as chymotrypsin, trypsin and papain. Therefore, protease detection
      kits based on fluorescein isothiocyanate-labeled casein were employed, and
      protease concentrations greater than 15 microg/mL of urine entailed subsequent 1
      dimensional gel electrophoretic visualization of urinary proteins. The presence
      of 20 microg of proteases per mL of urine caused a complete degradation of
      proteins usually observed in urinary matrices ("trace of burning"), while
      respective proteases were still detected in spiked urine samples after 10 days of
      storage at + 4 and - 20 degrees C. Identification of target proteases at
      respective molecular weights was accomplished using bottom-up sequencing
      approaches based on in-gel digestion of separated enzymes followed by capillary
      liquid chromatography--Orbitrap tandem mass spectrometry.

PMID- 17525884
TI  - Home-based walking improves cardiopulmonary function and health-related QOL in
      community-dwelling adults.
AB  - The objective of our study was to investigate the effects of a home-based walking
      program on physical fitness and QOL among community residents. Subjects (n = 200,
      mean age: 64.2 years, range: 42 - 75 years) who participated in the 32-week trial
      were randomly allocated to one of two groups: an exercise (E) group and a control
      (C) group. The E group was instructed to increase the number of steps a day that
      they walked and to perform aerobic walking at a target heart rate for 20 minutes
      or more daily, 2 or more days a week. The C group was told to continue their
      normal level of activity. Outcome measures were the 3-minute shuttle stamina walk
      test (SSWT), 30-second chair-stand test (CS-30), and SF-36. Increases in SSWT
      values were significantly greater in the E group than in the C group (men 24.1 m
      vs. 6.3 m; women 8.8 m vs. 2.4 m), as were increases in CS-30 values (men 5.9 vs.
      2.6; women 4.5 vs. - 0.1). On the SF-36, the scores in the E group for vitality
      and mental health increased significantly. Home-based walking is considered to be
      an effective and feasible method to improve physical fitness and QOL among
      community residents.

PMID- 17525885
TI  - The life and vision of a pioneer: a tribute to Tage Astrup, D.Sc., Dr.Med.h.c.

PMID- 17525887
TI  - Incidence and pathogenesis of thrombosis in hematologic malignancies.
AB  - Recent surveys have indicated that thromboembolic complications are at least as
      common in hematologic malignancies, if not more frequent, than in solid tumors.
      The pathogenesis of thrombosis is similar to that in solid tumors, but with
      additional factors unique in several forms of hematologic malignancies, as seen
      in acute promyelocytic leukemia, myeloma, and myeloproliferative disorders.
      Likewise, the factors contributing to bleeding are similar to those seen in solid
      tumors, with the exception of a higher frequency of thrombocytopenia.

PMID- 17525888
TI  - Thrombosis in myeloproliferative disorders: prevalence, prognostic factors, and
      the role of leukocytes and JAK2V617F.
AB  - An underlying myeloproliferative disorder (MPD), especially polycythemia vera
      (PV) or essential thrombocythemia (ET), is a risk factor for thrombosis.
      Considering large selected studies, prevalence rates for major thrombosis, at
      time of diagnosis, range from approximately 34 to 39% for PV and 10 to 29% for
      ET; the corresponding figures for thrombosis at follow-up are approximately 8 to
      19% for PV and 8 to 31% for ET. In all instances, arterial events were more
      frequent than venous events. In both PV and ET, advanced age and history of
      thrombosis are independent predictors of recurrent thrombosis. In addition,
      leukocytosis, but not thrombocytosis, has been identified as a potential risk
      factor for thrombosis in both diseases. The particular observation is consistent
      with the laboratory demonstration, in these disorders, of increased number of
      activated granulocytes and granulocyte-platelet aggregates, upregulation of
      platelet P-selectin and tissue factor expression by granulocytes, and the
      antithrombotic value of hydroxyurea therapy. Most recently, a JAK2 gain-of
      function mutation ( JAK2V617F) was described in virtually all patients with PV
      and approximately 50% of those with ET. Whether the presence of this specific
      mutation or its allele burden modifies the risk of thrombosis in patients with
      MPDs currently is under investigation.

PMID- 17525889
TI  - Therapy for polycythemia vera and essential thrombocythemia is driven by the
      cardiovascular risk.
AB  - The clinical course of polycythemia vera (PV) and essential thrombocythemia (ET)
      is characterized by an increased incidence of thrombotic and hemorrhagic
      complications and an inherent tendency to progress into myelofibrosis or acute
      myeloid leukemia. Major predictors of vascular events are increasing age and
      previous thrombosis. Myelosuppressive drugs can reduce the rate of thromboses and
      hemorrhages, but there is concern that their use accelerates the rate of leukemic
      transformation. Thus, a risk-oriented management strategy is recommended. Low
      risk patients with PV should be treated with phlebotomy and low-dose aspirin,
      whereas those with ET can be left untreated. Cytotoxic agents are recommended in
      high-risk cases and hydroxyurea is the drug of choice in most patients.
      Interferon alpha or anagrelide could be considered in selected young patients or
      as second-line therapy in those refractory or intolerant of hydroxyurea. The
      recent identification of JAK2V617F mutation in a substantial proportion of
      patients with PV and ET raises new questions regarding both risk classification
      and management, but additional studies on these issues are required.

PMID- 17525890
TI  - The double hazard of thrombophilia and bleeding in acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL), once highly fatal, has emerged as the most
      curable subtype of acute myeloid leukemia in adults. Cure is now expected in
      approximately 70 to 90% of patients when treatment includes all- TRANS retinoic
      acid (ATRA) combined with anthracycline-based chemotherapy. Early mortality most
      often is due to a severe and often catastrophic bleeding, often intracerebral in
      location, and remains a major cause of treatment failure. Thrombosis, either at
      diagnosis or during the course of treatment, may be unrecognized and reflects the
      complexity of the coagulopathy. The dual phenomenon of bleeding and thrombosis is
      attributable to at least three processes: disseminated intravascular coagulation;
      fibrinolysis (generated in part by expression of annexin-II on the APL cell
      surface); and direct proteolysis of several proteins including fibrinogen and von
      Willebrand factor. Both ATRA and arsenic trioxide are associated with rapid
      resolution of the coagulopathy. The use of heparin, once a mainstay of therapy
      for patients with APL, has been all but abandoned. Preliminary studies suggest no
      role for the routine use of antifibrinolytic agents. The most important
      therapeutic strategy is early institution of ATRA at the first suspicion of the
      diagnosis (without waiting for genetic confirmation) and aggressive blood product
      support during induction.

PMID- 17525891
TI  - Hemostatic dysfunction in paraproteinemias and amyloidosis.
AB  - Thrombotic and hemorrhagic complications frequently have been observed in
      patients with monoclonal gammopathy, Waldenstrom macroglobulinemia, amyloidosis,
      multiple myeloma (MM), and myeloma. Chemotherapy in combination with the use of
      antiangiogenic agents can further enhance the risk of cardiovascular
      complications. A malignancy-associated thrombophilic state (in particular,
      cytokine-induced high levels of factor VIII and von Willebrand factor) can also
      explain the high rate of thrombosis reported in these patients. Impaired
      fibrinolysis and a transient downregulation of the protein C system are recently
      discovered pathogenetic mechanisms. At diagnosis, when the highest VTE risk is
      present, baseline coagulation tests such activated protein C resistance may be
      helpful to identify patients who can benefit the most from anticoagulation; with
      the emerging evidence of a positive effect on survival of low molecular weight
      heparin, prospective trials are needed in this group of diseases.

PMID- 17525892
TI  - Therapeutic apheresis in hyperleukocytosis and hyperviscosity syndrome.
AB  - Therapeutic apheresis (TA), as a way of rapidly eliminating harmful or excessive
      blood components such as plasma proteins (plasma exchange) or cells
      (leukapheresis and platelet apheresis), has found broad application in a vast
      array of hematologic disorders. The most common hematologic indications for TA
      are leukocytosis in acute leukemias and hyperviscosity syndrome secondary to
      plasma cell dyscrasia. Leukapheresis is indicated in the initial management of
      leukostasis in patients with hyperleukocytosis in acute leukemias, particularly
      myeloid leukemias, or in patients who are at high risk of developing such a
      complication. Patients with lymphoid malignancies rarely develop leukostasis but
      may undergo cytoreduction with leukapheresis as prophylaxis for tumor lysis. The
      use of leukapheresis in acute promyelocytic leukemia is discouraged, given the
      possibility of increased risk of coagulopathy and bleeding. Similarly,
      therapeutic plasma exchange (TPE) represents an effective but temporary way of
      managing hyperviscosity syndrome secondary to immunoglobulin M paraproteins in
      patients with Waldenstrom macroglobulinemia. This review provides an overview of
      the pathophysiology of leukostasis and its management with leukapheresis. The use
      of TPE in the management of hyperviscosity syndrome is also discussed.

PMID- 17525893
TI  - Adverse effects on hemostatic function of drugs used in hematologic malignancies.
AB  - The adverse effects of drugs used in the treatment of hematologic malignancies
      are among the many factors contributing to the increased risk of both thrombosis
      and bleeding. These effects most often occur when combination of drugs are given.
      Some, such as L-asparaginase, result in both bleeding and thrombosis.
      Consideration must be given also to the bleeding or prothrombotic risk of the
      underlying hematologic disorder. The commonly used drugs with adverse effects on
      hemostasis include L-asparaginase, corticosteroids, inhibitors of vascular
      endothelial growth factor, gemtuzumab ozogamicin, thalidomide, and
      immunomodulatory derivatives of Thalidomide, and the hematopoietic growth
      factors. In addition, the syndrome of thrombotic microangiopathy may be brought
      on by several other drugs. Thus, a full understanding of these adverse effects is
      necessary in treating these disorders.

PMID- 17525894
TI  - Adverse effects of drugs used to treat hematologic malignancies: surveillance
      efforts from the research on adverse drug events and reports project.
AB  - Pharmaceuticals used to treat hematologic malignancies can lead to unexpected
      adverse events that involve a wide range of organ systems and physiological
      processes. The National Cancer Institute and National Heart Lung and Blood
      Institute-funded Research on Adverse Drug Events and Reports (RADAR) project-a
      collaboration of the Robert H. Lurie Comprehensive Cancer Center, the Department
      of Veterans Affairs, the Northwestern University Feinberg School of Medicine, and
      numerous academic institutions-identifies and evaluates unexpected adverse drug
      reactions associated with drugs used to treat malignant disorders. This article
      reviews the features of the safety program maintained by the U.S. Food and Drug
      Administration and the RADAR program.

PMID- 17525895
TI  - Hepatic veno-occlusive disease after hematopoietic stem cell transplantation:
      review and update on the use of defibrotide.
AB  - Veno-occlusive disease (VOD) of the liver remains one of the most feared
      complications associated with high-dose chemotherapy and hematopoietic stem cell
      transplantation (SCT). As a clinical syndrome characterized by fluid retention,
      hyperbilirubinemia, and painful hepatomegaly, VOD incidence varies widely, but it
      is universally recognized that severe cases of VOD have an extremely poor
      prognosis, with mortality at day 100 after SCT in excess of 80%. Systemic
      anticoagulant and thrombolytic therapies have been tested extensively in this
      disease, but are largely ineffective and are associated with significant bleeding
      complications. In recent years, defibrotide (DF; a polydisperse oligonucleotide
      derived from porcine intestinal mucosa with antithrombotic and protective
      properties on the microvasculature but minimal hemorrhagic risk) has emerged as a
      promising therapy for VOD. In large, multicenter, international phase I/II trials
      targeting patients with severe VOD, DF has been associated with complete response
      rates between 36 and 60%, survival past transplant day 100 in the range of 32 to
      50%, and few significant attributable side effects. On the basis of these
      encouraging results, a pivotal, prospective, multinational, phase III trial of DF
      is underway in patients with severe VOD, and should provide validation of this
      agent as a therapy for established disease with a high risk of mortality. This
      article reviews our current understanding of hepatic VOD after SCT and provides a
      summary of the data to date on the use of DF as both therapy and prophylaxis for
      this disease.

PMID- 17525896
TI  - Thromboembolic complications related to central venous access catheters in cancer
      patients.
AB  - Recent well-designed, prospective, controlled trials have demonstrated a lower
      incidence of catheter-related deep vein thrombosis (CRDVT) compared with earlier
      studies but this complication remains an important limitation to the delivery of
      drugs and supportive care to cancer patients. Prophylaxis of CRDVT with
      antithrombotic agents was not supported by recent prospective randomized trials,
      and its routine use is not recommended. Larger studies will be required to
      determine if cancer patients at particularly high risk for CRDVT can benefit from
      prophylaxis with antithrombotic agents. There are no prospective controlled
      studies to guide the therapy of CRDVT but treatment with anticoagulants remains
      the mainstay of therapy. Although recently published guidelines might help
      standardize the therapy of patients with CRDVT, prospective controlled studies
      are needed to determine the optimal therapy of this important complication of
      central venous catheters in cancer patients.

PMID- 17525897
TI  - Tumor lysis syndrome.
AB  - Tumor lysis syndrome (TLS) is an important metabolic disorder frequently
      encountered in the management of a variety of cancers including lymphoma,
      leukemia, and neuroblastoma. Delayed recognition can result in a variety of
      biochemical abnormalities resulting in life-threatening complications such as
      renal failure, arrhythmias, and seizures. Identification of high-risk patients
      and early recognition of the syndrome is crucial in the early institution of
      appropriate prophylaxis and treatment. Recent advances in the understanding of
      urate metabolism, development of new urate-lowering drugs, and the application of
      biomarkers, calculation methods, and prognostic models to identify high-risk
      patients will pave the way in improving the management of TLS. We included in
      this review the new information regarding the urate transporters URAT-1, organic
      anion transporter 1/3, and MRP4; the urate elimination pathway; a comparison of
      the old- (allopurinol, native uricase) and new- (febuxostat, Y-700, PEG-uricase,
      rasburicase) generation urate-lowering agents; and application of new biomarkers
      (cystatin-C, neutrophil gelatinase-associated lipocalin, kidney injury molecule
      1), estimated glomerular filtration rate and calculation methods (modification of
      diet in renal disease and prognostic model (Penn Predictive Score of Tumor Lysis
      Syndrome) in the identification of high-risk patients, and alternative unexplored
      mechanisms (asymmetric dimethylarginine and adenosine) to explain renal injury
      related to TLS.

PMID- 17525898
TI  - Hemorrhagic complications in pediatric hematologic malignancies.
AB  - Hematologic malignancies account for almost 40% of all cancers in children.
      Hemorrhage is the most common cause of early death in children with leukemia.
      Furthermore, major bleeding episodes lead to shorter survival and increased
      resource use. Potential risk factors for bleeding include hyperleukocytosis,
      immunophenotype of leukemia (especially acute promyelocytic leukemia),
      thrombocytopenia, and associated infections. Successful management of a bleeding
      episode is dependent on prompt identification of a child at high risk for
      bleeding, and should be directed at the replacement of blood products as well as
      to the aggressive therapy for underlying risk factors. Although in recent years
      there is a favorable decline in the hemorrhage-related mortality, the overall
      prevalence and the extent of morbidity posed by this potentially fatal
      complication, including disease outcome in children with hematologic malignancy,
      is largely unknown. In addition, there are no evidence-based guidelines for
      prophylactic blood or blood product transfusions. Prospective studies are
      required to define the epidemiology and risk factors predisposing children with
      hematologic malignancy to bleeding and to develop management guidelines.

PMID- 17525899
TI  - Thromboembolic complications in pediatric hematologic malignancies.
AB  - Thromboembolism (TE) is an uncommon entity in childhood. Overall 25% of children
      with thrombosis and more than 40% of children with central venous line (CVL) 
      related TE enrolled on the Canadian Pediatric Thrombophilia Registry had
      underlying diagnosis of cancer. However, so far there are very little data
      describing the epidemiology of TE in children with cancer. Most of the available
      information in this area originates mainly from retrospective and some
      prospective observational cohort studies conducted in children with acute
      lymphoblastic leukemia (ALL). Although ALL has been the most common cancer
      reported in association with thrombosis in children, available data from small
      studies indicate that TE is equally common in children with acute myeloid
      leukemia and lymphoma. TE in association with leukemia and lymphoma seems to be a
      multifactorial entity. Potential risk factors include increased thrombin
      generation related to leukemia, age of the patients, use of CVL, chemotherapy
      including asparaginase and corticosteroids, infections, and inherited
      prothrombotic state. Management of TE in a child with cancer presents a unique
      challenge in terms of balancing risk versus benefit. Conservative therapy could
      lead to clot extension and risks of additional morbidity or mortality; however,
      chemotherapy-related thrombocytopenia and coagulopathy increase the risk of
      bleeding complications. In summary, TE is a frequent and serious complication in
      children with hematologic malignancies. More prospective studies are required to
      define the epidemiology, pathogenesis, and management of TE in children with
      hematologic malignancies.

PMID- 17525900
TI  - Management of bleeding complications of hematologic malignancies.
AB  - Persons with hematologic malignancies bleed for a variety of reasons, including
      alterations in platelet function and numbers, clotting factor deficiencies,
      circulating anticoagulants, and defects in vascular integrity. The management of
      bleeding begins with a full characterization of the hemostatic defect. Vitamin K
      deficiency always should be considered and excluded by clinical history and
      laboratory tests. Localized bleeding is treated by packing, topical hemostatic
      agents, dressings, vessel ligation, laser beam coagulation, or embolization.
      Platelet transfusions are administered for hemorrhage secondary to severe
      platelet dysfunction or thrombocytopenia, but usually are not indicated if there
      is no bleeding, even though platelets may be as low as 10,000/microL. Bleeding
      due to thrombocytopenia that is refractory to random-donor platelets may respond
      to cross-matched compatible platelets, or to recombinant factor VIIa (rFVIIa).
      Fresh frozen plasma is indicated infrequently; bleeding due to coagulopathies is
      better managed with cryoprecipitate if fibrinogen is low, or with clotting factor
      concentrates appropriate for the specific clotting factors found to be deficient.
      rFVIIa or activated prothrombin complex concentrate usually controls hemorrhage
      due to autoantibodies directed against factor VIII, and acquired von Willebrand's
      disease may be responsive to desmopressin or intravenous gamma globulin infusion.
      Antifibrinolytic agents often enhance other hemostatic therapies, but should be
      withheld if there is genitourinary bleeding or evidence of disseminated
      intravascular coagulation. Finally, plasmapheresis and immunoadsorption to remove
      paraproteins may be helpful when other measures fail to curb bleeding.

PMID- 17525901
TI  - Management of thromboembolism in hematologic malignancies.
AB  - Patients with hematologic malignancies have increased risks of thromboembolism or
      bleeding. The commonest thrombotic complication is venous thromboembolism (VTE).
      Other thrombotic conditions occur in association with specific disorders, such as
      thrombotic thrombocytopenic purpura in hematopoietic stem cell transplantation
      and disseminated intravascular coagulation in acute promyelocytic leukemia.
      Clinical trials show that unfractionated heparin (UFH) and low molecular weight
      heparin (LMWH) are efficacious for VTE prophylaxis in cancer patients after major
      surgery or when hospitalized for acute medical illnesses. These findings in
      cancer patients are probably applicable to patients with hematologic
      malignancies, in whom there are very few studies. However, the effectiveness of
      anticoagulant VTE prophylaxis is not established in ambulatory patients with
      cancer except for multiple myeloma patients treated with thalidomide and
      chemotherapy. LMWH is widely used as initial treatment for VTE because it enables
      home therapy without laboratory monitoring, thereby improving the patient's
      quality of life. UFH is preferred in patients with high bleeding risks and renal
      impairment. In cancer patients, vitamin K antagonists for the long-term treatment
      of VTE are increasingly replaced by LMWH, which show superior efficacy. When
      prescribing anticoagulant prophylaxis or treatment to patients with hematologic
      malignancies, clinical benefits must be weighed carefully against the risks of
      bleeding.

PMID- 17525902
TI  - [Conceptual foundation of the operational diagnostic approach in psychiatry].
AB  - Based on the pioneering work of Emil Kraepelin, Karl Jaspers, Kurt Schneider and
      representatives of logical empiricism, the basic principles of the operational
      diagnostic approach in psychiatry are described. Operational diagnostic systems
      like ICD-10 and DSM-IV aimed at a standardisation of psychiatric language which
      can be accepted by different schools in psychiatry. However, ICD-10 and DSM-IV
      should not be misinterpreted as "nosology" because they do not reflect a specific
      model of psychiatric diseases. The advantages of operational diagnostic systems
      as instruments for communication in a clinical and scientific context are limited
      by the fact that they disregard the subjective psychopathology. This dimension,
      however, deserves attention in clinic and research.

PMID- 17525903
TI  - [In favour of a "new social psychiatry". Current focuses and trends of mental
      health care dealing between integrative and health economic perspectives].
AB  - Starting from modified sociodemographical, medical, familiar and health
      economical circumstances it is shown that in different areas of psychiatric
      supply fundamental offerings are missing or need to be established, thus one has
      to speak about an undersupply of certain groups (migrants, personality disorders,
      certain elderly patients). Some of these forward-looking trends and possible
      prospects in the field of social psychiatry are exemplarily displayed. The thesis
      is argued and illustrated that the existing social psychiatric institutions
      require a paradigmatic reorientation, which could be called "New Social
      psychiatry" and should complement the traditional social psychiatry, which has
      been orientated to schizophrenic illness, extramural alignment and the
      rehabilitation purpose of employment up to now.

PMID- 17525904
TI  - [Supporting research in pediatric oncology and hematology].

PMID- 17525905
TI  - Role of survivin splice variants in pediatric acute precursor B lymphoblastic
      leukemia.
AB  - BACKGROUND: Survivin, a member of the inhibitor of apoptosis protein (IAP) family
      is transiently expressed at low levels during normal hematopoesis but profoundly
      overexpressed in adult leukemia potentially contributing to leukemogenesis due to
      deregulated apoptosis and defective cell cycle control. Alternative splicing
      results in four different mRNA variants survivin, survivin2B, survivin-DeltaExon3
      and survivin-3B, with distinct cellular localization patterns and anti-apoptotic
      potential. Due to co-localization of survivin and survivin-2B in the cytoplasm
      survivin-2B may permit interactive fine-tuning of survivin actions and moreover
      play an attenuating role in its anti-apoptotic function. Lack of survivin-2B is
      associated with disease progression of malignomas suggesting a differential role
      of these isoforms in tumorigenesis. PATIENTS AND METHODS: We therefore determined
      the expression of the functional survivin splice variants performing RT- and real
      time PCR in a purely pediatric cohort of 20 patients suffering from precursor B
      ALL (BCP-ALL). RESULTS: Here, we demonstrate for the first time in pediatric
      patients with precursor B-ALL an association between lower survivin-2B expression
      and affiliation to the high risk group. CONCLUSION: The idea that survivin-2B may
      act as natural antagonist of survivin could potentially be used in novel
      approaches of anti-cancer treatment by influencing the proportional expression of
      the different splice variants.

PMID- 17525906
TI  - Daunorubicin-induced cell kill with 1-hour versus 24-hour infusions: a randomized
      comparison in children with newly diagnosed acute lymphoblastic leukemia.
AB  - BACKGROUND: Daunorubicin (DNR) is one of the most important drugs in treatment of
      acute lymphoblastic leukemia (ALL). Prolonged infusions of anthracyclines are
      less cardiotoxic but it has not been investigated whether the in vivo leukemic
      cell kill is equivalent to short-term infusions. PROCEDURE: In the cooperative
      treatment study COALL-92 for childhood ALL 178 patients were randomized to
      receive in a therapeutic window a single dose of 36 mg/m (2) DNR either as a 1-h
      (85 patients) or 24-h infusion (93 patients). Daily measurements of white blood
      cell count (WBC) and peripheral blood smears for seven days could be evaluated
      centrally in 101 patients (1-h: 43 patients, 24-h: 58 patients). RESULTS: The
      proportional decline of blasts at day 7 after DNR infusion showed no
      statistically significant difference between the two treatment arms. At day 3 the
      median percentage of blasts was less than 10%, at day 7 less than 2% for either
      the 1-h or 24-h infusion. Twelve patients (1-h: 5 patients, 24-h: 7 patients) had
      an absolute number of more than 1000 blasts per mul peripheral blood (PB) at day
      7 after DNR infusion (DNR poor responders). Kaplan-Meier analysis showed an equal
      probability of EFS for the short- and long-term infusion group (24-h: 83%+/-5; 1
      h: 81+/-6) after a median observation time of 12.3 years. CONCLUSIONS: We
      conclude that in children with ALL a 24-h infusion of DNR has the same in vivo
      cytotoxicity for leukemic cells as a 1-h infusion. This offers the possibility to
      use prolonged infusions with hopefully less cardiotoxicity without loss of
      efficacy.

PMID- 17525907
TI  - [Register for the evaluation of side effects after radiation in childhood and
      adolescence--first results].
AB  - BACKGROUND: Late effects after radiotherapy in childhood and adolescence have
      mainly been characterized retrospectively with small patient numbers. Therefore
      the German Group of Pediatric Radiation Oncology (APRO) established the "RegIster
      for the evaluation of late Side effects after radiation in childhood and
      adolescence" (RiSK). After a pilot phase starting in 2001 documentation has been
      performed all over Germany since 2004. This analysis shows the first results of
      "RiSK". PATIENTS AND METHODS: Radiation parameters including detailed organ doses
      as well as toxicity evaluations were collected prospectively from centers all
      over Germany in the study center. Standardized documentation forms were used.
      Documentation is planned for all children who receive radiotherapy in one of the
      German pediatric therapy trials. RESULTS: Until December 31st 2006, 696
      documentations of radiotherapy and 526 acute as well as 836 late follow-up
      documentation forms have been collected. Altogether, 41 patients with late grade
      3 and 16 patients with late grade 4-side effects were identified. Side effects
      mainly concerned joints with functional impairment (after combined radiotherapy
      and surgery), the bowel, skin and subcutis as well as blood parameters under
      continued chemotherapy. Patients with late side effects of a higher grade were
      mainly treated for Ewing's or soft tissue sarcomas (n=235 patients), representing
      33.8% of all patients in this study. CONCLUSION: Fortunately, up to now only a
      few late grade 3 or 4 side effects of radiotherapy are shown for almost 700
      documented patients. For further results, especially for the characterization of
      dose-effect-relationships, this study has to be continued with a higher patient
      number and a longer follow-up.

PMID- 17525908
TI  - Surgery in infants and children with testicular and paratesticular tumours: a
      single centre experience over a 25-year-period.
AB  - Testicular and even more paratesticular tumours in children are rare. The aim of
      the study is to characterise the spectrum of these lesions with focus on the
      feasibility and effectiveness of testis sparing surgery. Twenty-four boys treated
      between 1980 and 2004 at the University Leipzig Medical Centre were evaluated. At
      presentation patients were between 5 months and 18 years old (median 23 months).
      Generally a high rate of malignant or potentially malignant tumours was observed.
      The majority of these tumours occurred in the first three years of age. The
      spectrum of testicular tumours comprised 13 germ cell tumours (6 yolk sac
      tumours, 6 teratomas, 1 embryonal carcinoma) and 4 sex cord stromal tumours (2
      Leydig's cell, Sertoli's cell, granulosa cell). Both Leydig's cell tumours were
      endocrine active. Further on, we observed 3 boys with paratesticular
      rhabdomyosarcoma (RMS), and three with testicular and paratesticular metastases
      (Wilms' tumour, neuroblastoma, leukaemia). Serum alpha1-fetoprotein (AFP) was
      clearly elevated in 5 of 6 yolk sac tumours but remained within normal limits
      concerning the other entities. Human chorionic gonadotrophin was normal in all
      cases tested. During the observation period high inguinal orchidectomy was the
      surgical standard method. Dependent on tumour histology, stage and the
      recommended treatment schedule postoperative chemotherapy was added. Testis
      sparing surgery was performed in 3 boys with primary testicular tumours (2
      Leydig's cell, mature cystic teratoma). Local relapses were not observed.
      Systemic relapses occurred in 3 cases (2 RMS, leukaemia). During a median follow
      up of 5 years all patients with primary testicular tumours survived event free.
      Meta-analysis of the recent literature revealed that testis sparing surgery is
      feasible and save in prepubertal boys after exclusion of a malignant tumour. If a
      testis sparing approach is planned, the following criteria are essential: 1. The
      presence of a well defined circumscribed nodule confirmed by imaging. 2. Normal
      levels of serum AFP and hCG. 3. The presence of sufficient healthy testicular
      parenchyma. However, the high rate of malignant or potentially malignant tumours
      suggests that high inguinal orchidectomy should remain the surgical standard of
      therapy.

PMID- 17525909
TI  - Quality of survival in children and adolescents after treatment for childhood
      cancer: the influence of reported late effects on health related quality of life.
AB  - BACKGROUND: Considering the high survival rates of childhood cancer physical and
      psychosocial long term effects (LF) as well as the estimation of Quality of Life
      (QoL) are becoming a new focus of clinical research. Thus, disease related as
      well as age related variables have to be taken into account. This paper evaluates
      the physical long term effects of childhood cancer survivors. In addition
      differences of QoL of the survivors in comparison to children and adolescents of
      the same age are estimated if present and correlated to somatic late effects.
      PATIENTS AND METHODS: 36 survivors of childhood cancer who are followed at the
      University Children's Hospital Duesseldorf, with an age range of 8-18 years
      participate in the evaluation. Together with a clinical examination somatic long
      term effects and sociodemographic information are documented. QoL is evaluated
      with a standardized questionnaire (PEDQOL) including the domains physical
      function, emotion, cognition, autonomy, social function (family, friends and body
      image). Quality of Life data are compared with data of 319 unselected healthy
      controls of comparable age groups. RESULTS: 24 of 36 patients show various LF:
      skeletal deformities, scars, impairment of organ function, infectious
      complication, hormonal failures. Patients with solid tumors develop more and more
      frequently severe LF (11/14 pat.) compared to patients with leukaemia and
      lymphoma (11/22 pat.). Nevertheless health status can be objectively rated as
      satisfying in comparison to children of the same age. Most patients rate the QoL
      better than their controls. Patients with severe LF show impairment in the
      domains body image, emotional and physical functioning and cognition compared to
      patients without or with minor somatic LF. CONCLUSION: Our results underline the
      influence of objective long term effects and subjective QoL on the Quality of
      Survival. Prospective evaluation will lead to new and important information with
      respect to the onset of somatic and psychosocial LF and possible coping
      strategies. These information will establish additional possibilities for
      initiation of primary and secondary rehabilitation processes.

PMID- 17525910
TI  - Recent developments in iron chelation therapy.
AB  - Since 1962, desferrioxamine (deferoxamine, DFO) has been utilized for the
      treatment of secondary hemosiderosis. For about 30 years, DFO therapy has been
      performed as nightly continuous subcutaneous infusion. About 20 years ago, the
      first oral iron chelator (deferiprone, DFP) was presented. Concerns about
      potential side effects were responsible for the late acceptance and license of
      this drug which is limited to the use as second-line therapy for patients with
      thalassemia major. During recent years, chelation therapy and its evaluation
      started to progress rapidly. Clinical research and drug development as well as
      the introduction of new methods for the assessment of iron overload contributed
      to these advances. By using cardiac T2 (*) MRI it was possible to examine the
      specific effect of a chelator on myocardial siderosis. Clinical studies using
      this method indicated superiority of DFP compared to DFO with respect to the
      treatment of myocardial siderosis. Several retrospective and first prospective
      clinical trials seem to confirm this observation. In parallel, treatment
      strategies based on the combination of DFO and DFP have been developed. Using
      both drugs simultaneously or sequentially, additive and synergistic effects
      contribute to the fast elimination of iron from different organs at risk for
      siderotic damage. Deferasirox (DSX) is a recently developed oral chelator which
      shows good efficacy and tolerability in patients with transfusional hemosiderosis
      due to various underlying disorders. Long-term studies will define the future
      importance of DSX for iron chelation treatment. For the first time, there is a
      choice between three commercially available chelating agents for patients with
      transfusional iron overload. This will allow a highly effective, individually
      tailored treatment hopefully leading to a fundamental improvement of patients'
      life expectancy and quality.

PMID- 17525911
TI  - [Requirements and performance profile of the Paediatric Radiation Oncology
      Working Group (APRO): evaluation of the present situation and description of
      future developments].
AB  - BACKGROUND: Radiation therapy is an integral component in the management of
      childhood malignancies and undergoes a continuous process of optimization within
      the prospective trials of the GPOH. At present there are approximately 20 active
      protocols, some specifying radio-oncological study questions, in which about 500
      to 600 children annually are given radiotherapy. MATERIALS/METHODS: The Pediatric
      Radiation Oncology Working Group (APRO) of the German Society for Radiation
      Oncology (DEGRO) represents the organizational link between GPOH and DEGRO. Their
      activities range from phrasing guidelines of radio-oncological therapy, through
      writing a protocol for a prospective study on radiation-induced late effects
      (RISK--in co-operation with GPOH, 695 patients registered so far) and organizing
      meetings for information transfer, to implementing radio-oncology within the
      prospective studies of the GPOH by establishing study chairs for radio-oncology
      when radio-oncological questions are a primary focus and/or to function as a
      reference institution for quality assurance. These activities also include
      individual case consultations outside the study proper. Twice annually the
      members of the APRO meet for an update on current knowledge and future directions
      where a representative of the GPOH is invited to contribute special aspects of
      pediatric oncology. CONCLUSIONS: In the future, modern technology (intensity
      modulated radiotherapy, proton therapy, inclusion of imaging in treatment
      planning) will be part of disease management in pediatric oncology. A working
      group for modern radiotherapy technology was established to enhance this
      development. Prospective studies of the GPOH with primary or secondary radio
      oncological questions require the implementation of corresponding tasks
      (documentation, monitoring, etc.) in order to meet future demands on clinical
      trials and to achieve the aims of the protocol. Consequently adequate financial
      support is indispensable.

PMID- 17525912
TI  - [Position paper of the Society of Pediatric Oncology and Hematology (GPOH) on
      (long-term) surveillance, (long-term) follow-up and late effect evaluation in
      pediatric oncology patients].

PMID- 17525913
TI  - [Low-dose CT-guided transthoracic lung biopsy for evaluation of non-infectious
      chronic interstitial lung disease in children].
AB  - BACKGROUND: Children with interstitial pneumonitis (IP) of unknown origin often
      have to undergo open lung biopsy to establish a final diagnosis. Open lung biopsy
      is an invasive procedure with major potential complications. In the meantime, CT
      guided transthoracic lung biopsy (TLB) has become a common diagnostic procedure
      in adults. OBJECTIVE: The aim of this study was to retrospectively evaluate the
      efficacy and radiation exposure of low-dose CT-guided TLB in children with non
      infectious IP of unknown origin. METHODS: Twelve children (7-males, age range: 7
      months-15 years) with non-infectious IP of unknown origin and inconclusive
      clinical tests underwent CT-guided TLB with a 20-gauge biopsy instrument. A low
      dose protocol with acquisition of single slices was used on a 16-row CT scanner:
      80 kVp, 20 mAs, slice thickness 10 mm. Biopsy specimens were processed by
      standard histopathological and immunohistochemical techniques and effective doses
      were individually calculated. RESULTS: All biopsies were performed without major
      complications. Two children (17 %) developed a small pneumothorax/pulmonary
      haemorrhage that resolved spontaneously. A final diagnosis could be established
      in 9/12 patients (75 %) by CT-guided TLB. In 2 patients (17 %) the results of TLB
      were inconclusive; however, the clinical suspicion could be disproved. Open lung
      biopsy was performed in 1 patient (8 %), which demonstrated idiopathic pulmonary
      fibrosis. On average, the effective dose of CT-guided TLB was 0.78 mSv (0.4 - 1.1
      mSv). CONCLUSION: Low-dose CT-guided TLB can be a helpful method for
      investigating children with non-infectious IP of unknown origin thus making open
      lung biopsy unnecessary. Application of a low-dose protocol leads to a
      significant reduction of radiation exposure in CT-guided TLB.

PMID- 17525914
TI  - Synthesis of monodisperse spherical nanocrystals.
AB  - Much progress has been made over the past ten years on the synthesis of
      monodisperse spherical nanocrystals. Mechanistic studies have shown that
      monodisperse nanocrystals are produced when the burst of nucleation that enables
      separation of the nucleation and growth processes is combined with the subsequent
      diffusion-controlled growth process through which the crystal size is determined.
      Several chemical methods have been used to synthesize uniform nanocrystals of
      metals, metal oxides, and metal chalcogenides. Monodisperse nanocrystals of CdSe,
      Co, and other materials have been generated in surfactant solution by nucleation
      induced at high temperature, and subsequent aging and size selection.
      Monodisperse nanocrystals of many metals and metal oxides, including magnetic
      ferrites, have been synthesized directly by thermal decomposition of metal
      surfactant complexes prepared from the metal precursors and surfactants.
      Nonhydrolytic sol-gel reactions have been used to synthesize various transition
      metal-oxide nanocrystals. Monodisperse gold nanocrystals have been obtained from
      polydisperse samples by digestive-ripening processes. Uniform-sized nanocrystals
      of gold, silver, platinum, and palladium have been synthesized by polyol
      processes in which metal salts are reduced by alcohols in the presence of
      appropriate surfactants.

PMID- 17525915
TI  - CdpNPT, an N-prenyltransferase from Aspergillus fumigatus: overproduction,
      purification and biochemical characterisation.
AB  - A putative prenyltransferase gene, cdpNPT, was identified in the genome sequence
      of Aspergillus fumigatus by a homology search by using known prenyltransferases
      and sequence analysis. CdpNPT consists of 440 amino acids and has a molecular
      mass of about 50 kDa. The coding sequence of cdpNPT was cloned in pQE60 and
      overexpressed in E. coli. The soluble His(6)-fusion CdpNPT was purified to near
      homogeneity and characterised biochemically. The enzyme showed broad substrate
      specificity towards aromatic substrates and was found to catalyse the prenylation
      of tryptophan-containing cyclic dipeptides at N1 of the indole moieties in the
      presence of dimethylallyl diphosphate (DMAPP); geranyl diphosphate was not
      accepted as prenyl donor. The structures of the enzymatic products were
      elucidated by NMR and MS analysis. The K(m) value for DMAPP was determined to be
      650 microM. Due to substrate inhibition, K(m) values could not be obtained for
      the aromatic substrates. CdpNPT does not need divalent metal ions for its
      enzymatic reaction, although Ca(2+) enhances the reaction velocity by up to the
      threefold. CdpNPT is the first N-prenyltransferase that has been purified and
      characterised in a homogenous form after heterologous overproduction.
      Interestingly, it shows significant sequence similarity to other indole
      prenyltransferases that catalyse the formation of C--C bonds.

PMID- 17525916
TI  - Rescue of degradation-prone mutants of the FK506-rapamycin binding (FRB) protein
      with chemical ligands.
AB  - We recently reported that certain mutations in the FK506-rapamycin binding (FRB)
      domain disrupt its stability in vitro and in vivo (Stankunas et al. Mol. Cell,
      2003, 12, 1615). To determine the precise residues that cause instability, we
      calculated the folding free energy (Delta G) of a collection of FRB mutants by
      measuring their intrinsic tryptophan fluorescence during reversible chaotropic
      denaturation. Our results implicate the T2098L point mutation as a key
      determinant of instability. Further, we found that some of the mutants in this
      collection were destabilized by up to 6 kcal mol(-1) relative to the wild type.
      To investigate how these mutants behave in cells, we expressed firefly luciferase
      fused to FRB mutants in African green monkey kidney (COS) cell lines and mouse
      embryonic fibroblasts (MEFs). When unstable FRB mutants were used, we found that
      the protein levels and the luminescence intensities were low. However, addition
      of a chemical ligand for FRB, rapamycin, restored luciferase activity.
      Interestingly, we found a roughly linear relationship between the Delta G of the
      FRB mutants calculated in vitro and the relative chemical rescue in cells.
      Because rapamycin is capable of simultaneously binding both FRB and the
      chaperone, FK506-binding protein (FKBP), we next examined whether FKBP might
      contribute to the protection of FRB mutants. Using both in vitro experiments and
      a cell-based model, we found that FKBP stabilizes the mutants. These findings are
      consistent with recent models that suggest damage to intrinsic Delta G can be
      corrected by pharmacological chaperones. Further, these results provide a
      collection of conditionally stable fusion partners for use in controlling protein
      stability.

PMID- 17525917
TI  - Enhanced sensitivity of FRET-based protease sensors by redesign of the GFP
      dimerization interface.

PMID- 17525918
TI  - Effects of silicon nanowires on HepG2 cell adhesion and spreading.

PMID- 17525919
TI  - Asymmetric organocatalytic alpha-arylation of aldehydes.

PMID- 17525920
TI  - Ligand-exchange processes on solvated lithium cations: DMSO and water/DMSO
      mixtures.
AB  - Solutions of LiClO(4) in solvent mixtures consisting of dimethylsulfoxide (DMSO)
      and water, or DMSO and gamma-butyrolactone, were studied by (7)Li NMR
      spectroscopy (for complexation by cryptands in gamma-butyrolactone as a solvent,
      see: E. Pasgreta, R. Puchta, M. Galle, N. J. R. van Eikema Hommes, A. Zahl, R.
      van Eldik, J. Incl. Phen., 2007, 58, 81-88). Chemical shifts indicate that the
      Li(+) ion is coordinated by four DMSO molecules. In the binary solvent mixture of
      water and DMSO, no selective solvation is detected, thus indicating that on
      increasing the water content of the solvent mixture, DMSO is gradually displaced
      by water in the coordination sphere of Li(+). The ligand-exchange mechanism of
      Li(+) ions solvated by DMSO and water/DMSO mixtures was studied using DFT
      calculations. Ligand exchange on [Li(DMSO)(4)](+) was found to follow a limiting
      associative (A) mechanism. The displacement of coordinated H(2)O by DMSO in
      [Li(H(2)O)(4)](+) follows an associative interchange mechanism. The suggested
      mechanisms are discussed in reference to available experimental and theoretical
      data.

PMID- 17525921
TI  - Investigation of the stability of the M-H-B bond in borane sigma complexes
      [M(CO)5(eta1-BH2R.L)] and [CpMn(CO)2(eta1-BH2R.L)] (M=Cr, W; L=tertiary amine or
      phosphine): substituent and Lewis base effects.
AB  - We investigated the influence of a substituent and a Lewis base on boron upon the
      thermodynamic stability of metal complexes of borane-Lewis base adducts,
      [M(CO)5(eta1-BH(2)R.L)] (M=Cr, W) and [CpMn(CO)2(eta1-BH2R.L)], where R=Cl, I, m
      C6H4F, Ph, H, Me, Et; L=PMe3, PPh3, NMe3, quinuclidine. In these compounds, the
      stability of the metal-borane linkage was enhanced by increasing the electron
      releasing ability of the substituent on boron. A stronger base L additionally
      stabilized the complexes. The strength of the borane-metal interaction is thus
      mainly ascribed to the electron donation from the BH sigma orbital to metal
      rather than the back-donation into the BH sigma* orbital. This result supports
      the bonding model for the B-H-M linkage in the borane complexes suggested by MO
      calculations, where the borane-to-metal electron donation is predominant while
      the metal back-donation into the BH sigma* orbital is negligible. Such a
      stability trend of the borane complexes makes a sharp contrast to that of many
      silane and dihydrogen complexes.

PMID- 17525922
TI  - Porphyrin, phthalocyanine and porphyrazine derivatives with multifluorenyl
      substituents as efficient deep-red emitters.
AB  - The synthesis and photophysical properties are described for a series of
      porphyrin, phthalocyanine and pyrazinoporphyrazine derivatives which bear four or
      eight peripheral fluorenyl substituents as antennae. Representative examples are
      5,10,15,20-tetra(9,9-dihexyl-9H-fluoren-2-yl)porphyrin (2), 5,10,15,20-tetrakis[4
      (9,9-dihexyl-9H-fluoren-2-yl)phenyl]porphyrin (3), 2,3,9,10,16,17,23,24
      octakis(9,9-dihexyl-9H-fluoren-2-yl)-29H,31H-phthalocyanine (8) and
      2,3,9,10,16,17,23,24-octakis[4-(9,9-dihexyl-9H-fluoren-2-yl)phenyl]-29H,31H
      tetrapyrazinoporphyrazine (9). Palladium-mediated Suzuki-Miyaura cross-coupling
      reactions have been key steps for attaching the substituents. The compounds are
      deep-red emitters: lambda(max)(em)=659 (3), 737 (8) and 684 nm (9). Their
      absorption and emission spectra, their fluorescence lifetimes and quantum yields
      are correlated with the structures of the macrocycles and the substituents. The
      solution fluorescence quantum yields of porphyrin derivatives substituted with
      fluorene (2-4) and terphenyl substituents (7) (Phi(f)=0.21-0.23) are
      approximately twice that of tetraphenylporphyrin. For phthalocyanine derivative
      8, Phi(f) was very high (0.88). Specific excitation of the fluorene units of 8
      produced emission from both of them (lambda(max)=480 nm) and also from the
      phthalocyanine core (lambda(max)=750 nm), indicating a competitive rate of energy
      transfer and radiative decay of the fluorenes. Organic light-emitting devices
      (OLEDs) were made by spin-coating techniques by using a polyspirobifluorene
      (PSBF) copolymer as the host blended with 3 (5 wt. %) in the configuration
      ITO/PEDOT:PSS/PSBF copolymer:3/Ca/Al. Deep-red emission (lambda(max)=663 nm; CIE
      coordinates x=0.70, y=0.27) was observed with an external quantum efficiency of
      2.5 % (photons/electron) (at 7.5 mA cm(-2)), a low turn-on voltage and high
      emission intensity (luminance) of 5500 cd m(-2) (at 250 mA/ m(2)).

PMID- 17525923
TI  - Using a tripod as a chiral chelating ligand: chemical exchange between equivalent
      molecular structures in palladium catalysis with 1,1,1-tris(oxazolinyl)ethane
      ("trisox").
AB  - Threefold symmetrical chiral podands may simplify the stereochemistry of key
      catalytic intermediates for cases in which they only act as bidentate ligands.
      This applies to systems in which chemical exchange between the different kappa2
      coordinated forms takes place and in which the non-coordinated sidearm may play a
      direct or indirect role at some earlier or later stage in the catalytic cycle.
      Palladium(II)-catalysed allylic substitutions provide appropriate test reactions
      along these lines. A series of neutral dichloropalladium(II) complexes,
      [PdCl2(iPr-trisox)] (1a), [PdCl2(Ph-trisox)] (1b), [PdCl2(Bn-trisox)] (1c) and
      [PdCl2(Ind-trisox)] (1d) (trisox=1,1,1-tris(oxazolinyl)ethane) were synthesised
      by reaction of the respective trisox derivative with [PdCl2(PhCN)2] and
      characterised inter alia by 15N NMR spectroscopy. Direct detection of the
      heteronuclei without isotope enrichment and with "normal" sample concentrations
      was achieved with the aid of a cryogenically cooled NMR probe on a 600 MHz NMR
      spectrometer. Whereas the 15N nuclei of the coordinated oxazoline rings resonate
      at delta=160-167 ppm and appear as two singlets due to their diastereotopicity,
      the signal assigned to the dangling oxazoline "arm" is observed at delta=238-240
      ppm. Variable-temperature NMR studies along with a systematic series of
      magnetisation transfer experiments established exchange between ligating and non
      ligating oxazoline rings. Reaction of [Pd(allyl)(cod)]BF4 (cod=cyclooctadiene)
      with Ph-trisox in CH(2)Cl(2) gave the corresponding allyl complex 2, for which
      fast exchange between the three oxazoline heterocycles as well as between the exo
      and endo diastereomers was observed along with a very slow eta3-eta1-eta3 process
      of the allyl fragment (magnetisation transfer). Palladium(0) complexes were
      prepared by reaction of trisox derivatives or sidearm-functionalised BOX
      (BOX=bis(oxazolinyl)dimethylmethane) ligands with [Pd(nbd)(alkene)]
      (nbd=norbornadiene, alkene=maleic anhydride or tetracyanoethylene). X-ray
      diffraction studies of the iPr-trisox and Ph-trisox complexes (3a and 3b)
      established Y-shaped trigonal planar coordination geometries with the trisox
      ligand coordinated in a bidentate fashion, whilst the pi-coordinated maleic
      anhydride ligand adopts one of the two possible diastereotopic orientations. As
      the catalytic test reaction, the allylic alkylation of 1,3-diphenylprop-2-enyl
      acetate substrate with dimethyl malonate as nucleophile (in the presence of N,O
      bis(trimethylsilyl)acetamide) was investigated for the trisox derivatives, their
      BOX analogues, and a series of less symmetric "sidearm" functionalised
      bisoxazolines. The trisoxazoline-based catalysts generally induce a better
      enantioselectivity compared to their bisoxazoline analogues and display
      significant reduction of the induction period as well as rate enhancement.

PMID- 17525924
TI  - Approaching the megadalton: NMR spectroscopy of protein complexes.

PMID- 17525925
TI  - Relative energy computations with approximate density functional theory--a
      caveat!

PMID- 17525926
TI  - Recent advances in asymmetric phase-transfer catalysis.
AB  - The use of chiral nonracemic onium salts and crown ethers as effective phase
      transfer catalysts have been studied intensively primarily for enantioselective
      carbon-carbon or carbon-heteroatom bond-forming reactions under mild biphasic
      conditions. An essential issue for optimal asymmetric catalysis is the rational
      design of catalysts for targeted reaction, which allows generation of a well
      defined chiral ion pair that reacts with electrophiles in a highly efficient and
      stereoselective manner. This concept, together with the synthetic versatility of
      phase-transfer catalysis, provides a reliable and general strategy for the
      practical asymmetric synthesis of highly valuable organic compounds.

PMID- 17525931
TI  - Overestimation and underestimation of hepatitis C virus RNA levels in a widely
      used real-time polymerase chain reaction-based method.
AB  - The quantification of hepatitis C virus (HCV) RNA is essential for the everyday
      management of chronic hepatitis C therapy. Real-time polymerase chain reaction
      (PCR) techniques are potentially more sensitive than classical PCR techniques,
      are not prone to carryover contamination, and have a consistently wider dynamic
      range of quantification. Thus, they are rapidly replacing other technologies for
      the routine quantification of HCV RNA. We extensively evaluated the intrinsic
      characteristics and clinical performance of Cobas Ampliprep/Cobas TaqMan
      (CAP/CTM), the most widely used real-time PCR assay for HCV RNA quantification.
      This study shows that CAP/CTM is sensitive, specific, precise, and reproducible
      and has a broad dynamic range of quantification well suited to HCV RNA monitoring
      in clinical practice. However, we identified 2 technical issues that will have an
      impact in clinical practice. First, the CAP/CTM assay overestimates HCV RNA
      levels in undiluted patient samples by approximately 0.6 log(10) international
      units per milliliter on average, and this overestimation increases with the viral
      load. Second, the CAP/CTM assay substantially underestimates HCV RNA levels in
      approximately 15% of genotype 2 samples and 30% of genotype 4 samples, probably
      because of mismatches with the target sequences due to the primer and/or probe
      design. CONCLUSION: As the CAP/CTM platform is widely available, easy to use, and
      suited to high-throughput screening for viral genomes, the manufacturer should
      improve the HCV RNA kit to resolve these 2 important technical issues that may
      affect everyday management of hepatitis C therapy.

PMID- 17525932
TI  - A solution to the controversy between rate and temporal coding.
AB  - The apparent irregularity of in vivo spike sequences could be read as being
      derived either irregularly in time from a constant rate or regularly from a
      fluctuating rate. We recently proposed the Empirical Bayes method that selects
      one out of the alternative interpretations (J. Phys. A: Math. Gen. 2005; 38:L531
      L537). In this paper, we demonstrate that this method may also give a solution to
      the controversy between rate and temporal coding. For a given single sequence of
      spikes, the method may indicate two potential hypothetical rate processes, nearly
      constant and highly fluctuating, and selects one according to the statistical
      plausibility. As the rate fluctuation of a spike sequence is increased, the
      Bayesian interpretation exhibits a discontinuous transition from one to the
      other. In this way, a sequence of spikes can be distinctly categorized as either
      rate or temporal coding, according to the estimated degree of rate fluctuation.

PMID- 17525933
TI  - Effect of metabolic inhibitors on ATP and citrate content in PC3 prostate cancer
      cells.
AB  - BACKGROUND: In normal prostate epithelial cells low m-aconitase activity
      decreases citrate oxidation leading to citrate accumulation. In prostate cancer
      cells m-aconitase activity is increased and citrate content is lower. The effect
      of inhibition of m-aconitase on ATP production by prostate cancer cells (PC3) is
      not known nor is the contribution of glycolysis versus respiration. METHODS: ATP
      content of PC3 cells as affected by inhibition of m-aconitase (fluoroacetate
      (FA), zinc), inhibition of glycolysis (2DxG), or respiration (DNP, oligomycin)
      was determined. The ability to maintain ATP using glucose or glutamine as sole
      substrate was also determined. Intermediates including ATP, lactate, glucose, and
      glutamine were assayed in neutralized perchloric acid (PCA) cell extracts,
      virgin, and conditioned medium by enzymatic fluorometry. RESULTS: Data show that
      inhibition of m-aconitase, glycolysis, or respiration alone did not decrease ATP
      content. Inhibition of both glycolysis and respiration were required to decrease
      ATP content. PC3 cells were able to produce ATP with either glucose or glutamine
      as sole substrate. Though FA clearly inhibited m-aconitase there was no evidence
      that zinc had a similar effect. CONCLUSION: PC3 cells can support ATP production
      when m-aconitase is inhibited by using glycolysis or oxidation of substrate
      (e.g., glutamine) entering the TCA cycle distal to citrate.

PMID- 17525934
TI  - Significant variations in nuclear structure occur between and within Gleason
      grading patterns 3, 4, and 5 determined by digital image analysis.
AB  - BACKGROUND: Alterations in nuclei structure and DNA content captured from Gleason
      grading patterns 3, 4 and 5 of radical prostatectomy (RP) cases were determined
      by a computer-assisted microscope. Quantitative Nuclear Morphometry (QNM)
      profiles were created to evaluate variability in nuclear structure within each of
      these grades. METHODS: A tissue microarray (TMA) was constructed using RP cases
      and the prostate cancer (PCa) TMA cores prepared from 20 GG-3, 9 GG-4, 10 GG-5
      patterns, and 20 benign cancer-adjacent cases from RP archival paraffin blocks.
      Feulgen-stained nuclei were captured from 0.6 mm spots using the AutoCyte system.
      Pools of 1100 nuclei captured from each test group were used to calculate
      Multivariate Logistic Regression (MLR) models that generated predictive indices
      and predictive probabilities (PP) to make comparisons between and within each set
      of pooled nuclei. RESULTS: A single QNM profiles yielded areas of receiver
      operator characteristic curves (ROC) that distinguished differences among benign
      cancer-adjacent nuclei and GG-3 (ROC-AUC = 0.78); GG-4 (ROC-AUC = 0.86) and GG-5
      (ROC-AUC = 0.88) with accuracies of 73%, 78% and 80% respectively. Applying PP
      plots generated from MLR models of GG 3, 4, and 5 nuclei clearly demonstrated
      marked heterogeneity within each of these three GG patterns. CONCLUSIONS: QNM
      signatures illustrate alterations in nuclei structure, based upon nuclear
      morphometry within each of these three GG patterns, and might signify potential
      variations in PCa disease risk of progression outcomes. In the future a modified
      system of Gleason grading that considers not only glandular architecture but also
      quantitative nuclear grade may ensure accuracy in prognosis.

PMID- 17525935
TI  - Bounds on potential risks and causal risk differences under assumptions about
      confounding parameters.
AB  - Nonparametric bounds on causal effects in observational studies are available
      under deterministic potential-outcome models. We derive narrower bounds by adding
      assumptions regarding bias due to confounding. This bias is defined as the
      difference between the expectation of potential outcomes for the exposed group
      and that for the unexposed group. We show that crude effect measures bound causal
      effects under the given assumptions. We then derive bounds for randomized studies
      with noncompliance, which are given by the per protocol effect. With perfect
      compliance in one treatment group, the direction of effect becomes identifiable
      under our assumptions. Although the assumptions are not themselves identifiable,
      they are nonetheless reasonable in some situations.

PMID- 17525936
TI  - Visualization of three-dimensional nephron structure with microcomputed
      tomography.
AB  - The three-dimensional architecture of nephrons in situ and their
      interrelationship with other nephrons are difficult to visualize by microscopic
      methods. The present study uses microcomputed X-ray tomography (micro-CT) to
      visualize intact nephrons in situ. Rat kidneys were perfusion-fixed with buffered
      formalin and their vasculature was subsequently perfused with radiopaque
      silicone. Cortical tissue was stained en bloc with osmium tetroxide, embedded in
      plastic, scanned, and reconstructed at voxel resolutions of 6, 2, and 1 microm.
      At 6 microm resolution, large blood vessels and glomeruli could be visualized but
      nephrons and their lumens were small and difficult to visualize. Optimal images
      were obtained using a synchrotron radiation source at 2 microm resolution where
      nephron components could be identified, correlated with histological sections,
      and traced. Proximal tubules had large diameters and opaque walls, whereas distal
      tubules, connecting tubules, and collecting ducts had smaller diameters and less
      opaque walls. Blood vessels could be distinguished from nephrons by the luminal
      presence of radiopaque silicone. Proximal tubules were three times longer than
      distal tubules. Proximal and distal tubules were tightly coiled in the outer
      cortex but were loosely coiled in the middle and inner cortex. The connecting
      tubules had the narrowest diameters of the tubules and converged to form arcades
      that paralleled the radial vessels as they extended to the outer cortex. These
      results illustrate a potential use of micro-CT to obtain three-dimensional
      information about nephron architecture and nephron interrelationships, which
      could be useful in evaluating experimental tubular hypertrophy, atrophy, and
      necrosis.

PMID- 17525938
TI  - Scaling of the first ethmoturbinal in nocturnal strepsirrhines: olfactory and
      respiratory surfaces.
AB  - Turbinals (scroll bones, turbinates) are projections from the lateral wall of the
      nasal fossa. These bones vary from simple folds to branching scrolls.
      Conventionally, maxilloturbinals comprise the respiratory turbinals, whereas
      nasoturbinals and ethmoturbinals comprise olfactory turbinals, denoting the
      primary type of mucosa that lines these conchae. However, the first ethmoturbinal
      (ETI) appears exceptional in the variability of it mucosal covering. Recently, it
      was suggested that the distribution of respiratory versus olfactory mucosae
      varies based on body size or age in strepsirrhine primates (lemurs and lorises).
      The present study was undertaken to determine how the rostrocaudal distribution
      of olfactory epithelium (OE) versus non-OE scales relative to palatal length in
      strepsirrhines. Serially sectioned heads of 20 strepsirrhines (10 neonates, 10
      adults) were examined for presence of OE on ETI, rostral to its attachment to the
      nasal fossa wall (lateral root). Based on known distances between sections of
      ETI, the rostrocaudal length of OE was measured and compared to the length lined
      solely by non-OE (primarily respiratory epithelium). In 13 specimens, the total
      surface area of OE versus non-OE was calculated. Results show that the length of
      non-OE scales nearly isometrically with cranial length, while OE is more
      negatively allometric. In surface area, a lesser percentage of non-OE exists in
      smaller species than larger species and between neonates and adults. Such results
      are consistent with recent suggestions that the olfactory structures do not scale
      closely with body size, whereas respiratory structures (e.g., maxilloturbinals)
      may scale close to isometry. In primates and perhaps other mammals, variation in
      ETI morphology may reflect dual adaptations for olfaction and endothermy.

PMID- 17525939
TI  - Expression of caveolin-3 in the fibroblast-like type B synoviocytes in the rat
      temporomandibular joint.
AB  - The present study revealed that the fibroblast-like type B synoviocytes (covering
      the surface of the synovial membrane in the rat temporomandibular joint) had
      muscle-specific caveolin-3 protein in their caveolae. The existence of two kinds
      of type B synoviocytes (with and without caveolin-3-immunoreactions even in the
      synovial lining layer) might reflect the functional difference between them.

PMID- 17525940
TI  - A novel phenotypic marker for ATM-deficient 129S6/SvEvTac-ATMtm1Awb/J mice.
AB  - Ataxia-telangiectasia (A-T) is a human autosomal recessive disorder characterized
      by neuronal degeneration as well as many other physiological and somatic defects.
      ATM (A-T, mutated), the gene mutated in A-T, encodes a 370 kDa protein kinase.
      ATM knockout mouse models (ATM(-/-)) show growth retardation, infertility,
      neurological dysfunction, defects in T-lymphocytes, and extreme sensitivity to
      ionizing radiation. We have recently established multiple ATM(+/-) breeding pairs
      and discovered that all ATM(-/-) offspring exhibit a nonpigmented section of
      tail, usually at or near the tip. To our knowledge, this is the first time that a
      phenotype of nonpigmented tail has been reported in ATM(-/-) knockout mice. We
      believe that the sections of nonpigmented tail of 129S6/SvEvTac-ATM(tm1Awb)/J
      mice provide a novel phenotypic marker for research using this ATM knockout mouse
      model. Results from histochemistry and immunoblotting analysis further
      demonstrate that while melanocyte precursors or melanoblasts are present in the
      nonpigmented tail tissue of ATM(-/-) mice, they fail to differentiate fully into
      mature melanocytes. The potential connection between this phenotype and other
      clinical symptoms caused by ATM deficiency, such as progressive neuronal
      degeneration, is discussed in this article.

PMID- 17525941
TI  - Aberrant differentiation of the axially condensed tail bud mesenchyme in human
      embryos with lumbosacral myeloschisis.
AB  - Development of the posterior neural tube (PNT) in human embryos is a complicated
      process that involves both primary and secondary neurulation. Recently, we
      histologically examined 20 human embryos around the stage of posterior neuropore
      closure and found that the axially condensed mesenchyme (AM) intervened between
      the neural plate/tube and the notochord in the junctional region of the primary
      and secondary neural tubes. The AM appeared to be incorporated into the most
      ventral part of the primary neural tube, and no cavity was observed in the AM. In
      this study, we report three cases of human embryos with myeloschisis in which the
      open primary neural tube and the closed secondary neural tube overlap
      dorsoventrally. In all three cases, part of the closed neural tube was located
      ventrally to the open neural tube in the lumbosacral region. The open and closed
      neural tubes appeared to be part of the primary and the AM-derived secondary
      neural tubes, respectively. Thus, these findings suggest that, in those embryos
      with myeloschisis, the AM may not be incorporated into the ventral part of the
      primary neural tube but aberrantly differentiate into the secondary neural tube
      containing cavities, leading to dorsoventral overlapping of the primary and
      secondary neural tubes. The aberrant differentiation of the AM in embryos with
      lumbosacral myeloschisis suggests that the AM plays some roles in normal as well
      as abnormal development of the human posterior neural tube.

PMID- 17525942
TI  - Computerized three-dimensional analysis of the heart and great vessels in normal
      and holoprosencephalic human embryos.
AB  - The developing heart and great vessels undergo drastic morphogenetic changes
      during the embryonic period. To analyze the normal and abnormal development of
      these organs, it is essential to visualize their structures in three and four
      dimensions, including the changes occurring with time. We have reconstructed the
      luminal structure of the hearts and great vessels of staged human embryos from
      serial histological sections to demonstrate their sequential morphological
      changes in three dimensions. The detailed structures of the embryonic heart and
      major arteries in normal and holoprosencephalic (HPE) human embryos could be
      reconstructed and visualized, and anatomical structures were analyzed using 3D
      images. By 3D analysis, cardiac anomalies such as double-outlet right ventricle
      and malrotation of the heart tube were identified in HPE embryos, which were not
      easily diagnosed by histological observation. Reconstruction and analysis of 3D
      images are useful for the study of anatomical structures of developing embryos
      and for identifying their abnormalities.

PMID- 17525943
TI  - Three-dimensional Procrustes analysis of modern human craniofacial form.
AB  - The objective of this study was to analyze modern human craniofacial form using
      3D Procrustes superimposition in order to establish a reference model and
      validate it on computed tomography (CT). The sample consists of 136 specimens
      from five modern human regional groups. Thirty-three craniofacial landmark
      coordinates have been recorded using a Microscribe and calculated on CT scans for
      five crania from the sample. Procrustes superimposition has been performed to
      calculate the mean shape, and a discriminant analysis has also been carried out
      to estimate the variability of shape. The results show that the repeatability of
      measurements made on CT and on Microscribe is excellent (R = 0.99). There is no
      major distinctiveness in the craniofacial shape; however, discriminant function 1
      separates out the European crania from the others, especially African and
      American. It includes the width and the length of the face, the flatness of the
      upper face, the prognathism of the maxilla, as well as the length and the
      inclination of the palate. The width of the maxilla and the palate do not show a
      great variability. This may be the common invariant feature responsible for the
      alignment of the teeth in all specimens. It may correspond to functional patterns
      related to masticatory constraints manifested by the important interproximal and
      occlusal dental wear in all specimens. This study confirms the high accuracy of
      measurements made on CT scan and the importance of geometric morphometrics, which
      provides an accurate characterization of the overall craniofacial shape and its
      variation within the entire population.

PMID- 17525944
TI  - Ontogenetic structural and material variations in ovine calcanei: a model for
      interpreting bone adaptation.
AB  - Experimental models are needed for resolving relative influences of genetic,
      epigenetic, and nonheritable functionally induced (extragenetic) factors in the
      emergence of developmental adaptations in limb bones of larger mammals. We
      examined regional/ontogenetic morphologic variations in sheep calcanei, which
      exhibit marked heterogeneity in structural and material organization by skeletal
      maturity. Cross-sections and lateral radiographs of an ontogenetic series of
      domesticated sheep calcanei (fetal to adult) were examined for variations in
      biomechanically important structural (cortical thickness and trabecular
      architecture) and material (percent ash and predominant collagen fiber
      orientation) characteristics. Results showed delayed development of variations in
      cortical thickness and collagen fiber orientation, which correlate with
      extragenetic factors, including compression/tension strains of habitual bending
      in respective dorsal/plantar cortices and load-related thresholds for
      modeling/remodeling activities. In contrast, the appearance of trabecular arches
      in utero suggests strong genetic/epigenetic influences. These stark
      spatial/temporal variations in sheep calcanei provide a compelling model for
      investigating causal mechanisms that mediate this construction. In view of these
      findings, it is also suggested that the conventional distinction between genetic
      and epigenetic factors in limb bone development be expanded into three
      categories: genetic, epigenetic, and extragenetic factors.

PMID- 17525945
TI  - Structure and chemical organization of the accessory olfactory bulb in the goat.
AB  - The structure and chemical composition of the accessory olfactory bulb (AOB) were
      examined in male and female goats. Sections were subjected to either Nissl
      staining, Kluver-Barrera staining, lectin histochemistry, or immunohistochemistry
      for nitric oxide synthase (NOS), neuropeptide Y (NPY), tyrosine hydroxylase (TH),
      dopamine beta-hydroxylase (DBH), and glutamic acid decarboxylase (GAD). The goat
      AOB was divided into four layers: the vomeronasal nerve layer (VNL), glomerular
      layer (GL), mitral/tufted (M/T) cell layer (MTL), and granule cell layer (GRL).
      Quantitative and morphometric analyses indicated that a single AOB contained
      5,000-8,000 putative M/T cells with no sex differences, whereas the AOB was
      slightly larger in males. Of the 21 lectins examined, 7 specifically bound to the
      VNL and GL, and 1 bound not only to the VNL, but also to the MTL and GRL. In
      either of these cases, no heterogeneity of lectin staining was observed in the
      rostrocaudal direction. NOS-, TH-, DBH-, and GAD-immunoreactivity (ir) were
      observed in the MTL and GRL, whereas NPY-ir was present only in the GRL. In the
      GL, periglomerular cells with GAD-ir were found in abundance, and a subset of
      periglomerular cells containing TH-ir was also found. Double-labeling
      immunohistochemistry revealed that virtually all periglomerular cells containing
      TH-ir were colocalized with GAD-ir.

PMID- 17525946
TI  - Comparative spermatogenesis, spermatocytogenesis, and spermatozeugmata formation
      in males of viviparous species of clinid fishes (Teleostei: Clinidae,
      Blennioidei).
AB  - Spermatogenesis and spermatocytogenesis in 16 species of viviparous clinid fishes
      (Clinidae, Blennioidei) from various localities were followed for the first time
      by means of light and electron microscopy. The testes of the studied species are
      of the lobular type, with germinal stem cells situated at the apical ends of the
      lobules and a vas efferens along the internal margin. Maturation of the
      spermatides takes place in spermatocysts formed by Sertoli cells around the B
      spermatogonia. The gradual condensation and relocation of the chromosomes along
      the nuclei membranes are highly prominent in this process, which can be divided
      into several stages. Anisodiametric and slightly flattened sperm heads are
      eventually formed, 0.4-0.5 microm in diameter and 7.5 +/- 1 microm long, bearing
      80 +/- 15 microm long flagella. The sperms are packed into spermatozeugmata
      within the spermatocysts, enveloped and penetrated by the mucotic material of the
      Sertoli cells. With division of the germ cells and maturation of the spermatids,
      the spermatocyst dimensions increase, attaining 40 +/- 8 microm in diameter in
      the smaller species of Heteroclinus, and up to 90 +/- 10 microm in the larger
      males of Clinus superciliosus and C. cottoides. Accordingly, the volume of the
      maturing spermatocysts attains ca. 1,300 +/- 100 microm(3) in the smaller
      species, and ca. 6,500 +/- 300 microm(3) in the larger ones. As sperm head volume
      is ca. 2.24 microm(3), the number of sperm in the smallest mature spermatocysts
      reaches ca. 440 and in the largest over 2,900. Upon release from the cysts, the
      spermatozeugmata are transported along the sperm ducts to the posterior ampullae
      where they are stored in the epididymis. During copulation, the sperms are
      transported from there to the female via the intromittent organ. The sperm
      formation parameters and their structure and numbers are discussed.

PMID- 17525947
TI  - A re-evaluation of gelsolin at ectoplasmic specializations in sertoli cells: the
      influence of serum in blocking buffers on staining patterns.
AB  - In this study, we test the hypothesis that gelsolin immunolocalized in actin
      filament-rich ectoplasmic specializations may be exogenous gelsolin present in
      normal serum used in blocking buffers, and that binds to the intercellular
      adhesion plaques during tissue processing. Fixed frozen sections of rat and
      rabbit testis were pre-treated with standard blocking buffers containing 5%
      normal goat serum (NGS) and then incubated with anti-gelsolin antibodies in the
      presence of 1% NGS. Other sections were treated in a similar fashion, but in
      buffers not containing NGS. Sections were then labeled with secondary antibody
      conjugated to a fluorochrome. Localized staining at ectoplasmic specializations
      occurred only in sections treated with NGS. The only positive staining in
      sections not treated with NGS was associated with seminiferous tubule walls and
      blood vessels in rabbit tissue. The antibodies reacted with a single band at the
      appropriate molecular weight for gelsolin on immunoblots of NGS, but did not
      react on immunoblots of testis or seminiferous epithelium. We conclude that
      gelsolin localized at ectoplasmic specializations using current commercially
      available antibodies is a result of non-specific binding to the fixed tissues of
      gelsolin present in blocking buffers.

PMID- 17525948
TI  - Neocortical and hippocampal neuron and glial cell numbers in the rhesus monkey.
AB  - The rhesus monkey is widely used as an experimental animal model in the study of
      brain function and disease. While previous quantitative studies have provided
      knowledge of regional numbers, little is known of the total neocortical neuron
      and glial cell numbers in this species. The aim of this study is to establish
      quantitative norms. We use the optical fractionator and Cavalieri principle to
      examine the right hemisphere of eight young rhesus monkeys taken from the control
      group of an ongoing study. Applying these methods to agar-embedded and vibratome
      sectioned tissue, we generate estimates of cell numbers and regional volumes of
      neocortical and hippocampal regions with coefficients of variance (CV) around
      10%. The mean unilateral neocortical neuron number is 1.35 x 10(9) (CV +/- 0.10)
      and the mean unilateral neocortical glial cell number is 0.78 x 10(9) (CV +/-
      0.17). Mean unilateral neocortical volume is found to be 8.5 (CV +/- 0.10) cm(3)
      after processing, or 19 cm(3) when correcting for shrinkage. The neuron/glia
      ratio is 1.77. The neurons are distributed with 18% in the frontal cortex, 57% in
      the temporal and parietal cortices, and 25% in the occipital cortex. In the
      hippocampal subregions, we found unilateral neuron number of 1.72 x 10(6) (CV +/-
      0.13) and glial number of 2.25 x 10(6) (CV +/- 0.17) in CA1, and 0.80 x 10(6) (CV
      +/- 0.27) neurons and 1.05 x 10(6) (CV +/- 0.26) glial cells in CA2-3.
      Comparisons with related studies show quantitative variation, but also variations
      in methods and applications. The results are phylogenetically consistent, apart
      from the neuron/glia ratio, which is remarkably higher than what is found in
      other species.

PMID- 17525949
TI  - Light-dependent retinal innervation of the rat superior colliculus.
AB  - Mammalian retinal projections are divided into two anatomically and functionally
      distinct systems: the primary visual system, which mediates conscious visual
      processing, and the subcortical visual system, which mediates nonconscious
      responses to light. Light deprivation during a critical period in development
      alters the anatomy, physiology, and function of the primary visual system in many
      mammalian species. However, little is known about the influence of dark-rearing
      on the development of the subcortical visual system. To evaluate whether the
      early lighting environment alters the anatomy of the subcortical visual system,
      we examined the retinas and retinofugal projections of rats reared in a 12:12
      light/dark cycle or in constant dark from birth to 4 months of age. We found that
      dark-rearing was associated with a reduction in the distribution of retinal
      fibers in the stratum opticum of the contralateral superior colliculus. In
      contrast to the plasticity of the retinocollicular projection, retinal input to
      sleep, circadian, and pupillary control centers in the hypothalamus, pretectum,
      and lateral geniculate complex was unaffected by dark-rearing. A decrease in
      retinal innervation of the stratum opticum and intermediate layers of the
      superior colliculus may account for some of the deficits in multisensory
      integration that have been observed in dark-reared animals of several species.

PMID- 17525950
TI  - Cortical connections of the middle temporal and the middle temporal crescent
      visual areas in prosimian galagos (Otolemur garnetti).
AB  - While considerable progress has been made in understanding the organization of
      visual cortex in monkeys, less is known about the visual systems of prosimians.
      The middle temporal visual area (MT), an area involved in motion perception, is
      common to all primates. We placed injections of tracers in MT and just caudal to
      MT in cortex expected to be the MT crescent (MTc), an area previously identified
      in monkeys but not in prosimians. We analyzed the patterns of projections in
      sections of the flattened cortex and used sections stained for cytochrome oxidase
      (CO) and myelin to identify the borders of MT, MTc, middle superior temporal
      (MST), superior temporal sulcus (FST), and V1 and V2 and to identify possible
      subdivisions of these areas. As in owl monkeys, MTc is a belt around most of MT
      that consists of a single row of CO-dense patches in a CO-light surround.
      Injections placed in MT revealed connections with V1, V2, V3, FST, MST, MTc,
      dorsomedial, dorsolateral (DL), posterior parietal cortex, and inferotemporal
      (IT) cortex. Injections localized to MTc displayed a slightly different pattern
      of connections with more involvement of DL and IT cortex, though other aspects,
      including patchy connections with V1 and V2, were similar to MT connections. The
      results indicate that prosimian galagos have an MT area with connection patterns
      that are similar to those in New and Old World monkeys. The MTc, initially
      described in owl monkeys, is present in galagos and is likely to be a common
      component of primate visual cortex.

PMID- 17525951
TI  - Regional cerebral blood flow after recovery from anorexia or bulimia nervosa.
AB  - OBJECTIVE: Abnormalities of regional cerebral blood flow (rCBF) have been found
      in individuals who are ill with anorexia (AN) or bulimia nervosa (BN). Little is
      known about whether rCBF normalizes after recovery from AN and BN. METHOD:
      Eighteen control women (CW), 10 recovered restricting type AN, 8 recovered AN
      with a binging history, and 9 recovered BN participants without a history of AN
      were studied using positron emission tomography and [(15)O]water in order to
      assess rCBF. RESULTS: Partial volume corrected rCBF values in cortical and
      subcortical brain regions were similar between groups. Neither current body mass
      index nor age correlated with rCBF values. CONCLUSION: The results from this
      study indicate that rCBF normalizes with long-term recovery. Thus, altered rCBF
      is unlikely to confound functional imaging studies in AN or BN after recovery.

PMID- 17525952
TI  - What does viewing a pro-anorexia website do? An experimental examination of
      website exposure and moderating effects.
AB  - OBJECTIVE: This study experimentally examined the effects of viewing a pro
      anorexia website. METHOD: Following construction of a prototypic pro-anorexia
      website, 235 female undergraduates were randomly assigned to view either the pro
      anorexia website or one of two comparison websites related to female fashion
      (using average-sized models) or home decor. Post-website affect, cognitions, and
      behavioral expectations were examined along with moderator effects. RESULTS:
      Study participants exposed to the pro-anorexia website had greater negative
      affect, lower social self-esteem, and lower appearance self-efficacy post-website
      than those who viewed a comparison website. Additionally, they perceived
      themselves as heavier, reported a greater likelihood of exercising and thinking
      about their weight in the near future, and engaged in more image comparison.
      Minimal support was found for moderator effects. CONCLUSION: Results provide an
      empirical basis for concern (expressed by clinicians, researchers, the media)
      that pro-anorexia websites are a troubling new form of thin-ideal exposure that
      warrants further examination.

PMID- 17525953
TI  - Discordant lymphatic drainage patterns revealed by serial lymphoscintigraphy in
      cutaneous head and neck malignancies.
AB  - BACKGROUND: We analyzed the variability and accuracy of sentinel lymph node (SLN)
      identification by lymphoscintigraphy performed preoperatively and repeated on the
      day of operation in patients with melanoma or Merkel cell cancer. METHODS: Twenty
      five prospectively studied patients had lymphoscintigraphy prior to and on the
      day of operation. Discordance between lymphoscintograms was defined as change in
      location of SLN or failure to identify a SLN by one of the studies. RESULTS: In
      22 of 24 assessable cases (92%), SLNs were excised. Preoperative
      lymphoscintigraphy was correct in 19 of 22 (86%) cases. Day of operation
      lymphoscintigraphy was correct in 20 of 22 (91%) cases. SLN location was as
      classically described in 24 of 25 (96%) cases. Discordance between
      lymphoscintigraphy studies was 32% (8/25 patients). Half with discordant
      migration (8%) yielded metastases in basins not identified by day of operation
      lymphoscintigraphy but demonstrated by preoperative lymphoscintigraphy.
      CONCLUSIONS: Head and neck lymphatic drainage patterns not only vary between
      patients but also can vary with time for a single patient.

PMID- 17525954
TI  - Are babies better in autumn or spring? The consequences of extending gestation in
      a biennially reproducing viviparous lizard.
AB  - Niveoscincus microlepidotus, the southern snow skink, is a biennially reproducing
      alpine viviparous lizard with an extremely protracted gestation period: embryos
      are fully developed in autumn, but held over winter so that offspring are born in
      spring. The obvious benefits for offspring survival of delaying birth until
      spring have been demonstrated previously. To examine the consequences of deferred
      parturition for offspring characteristics, we compared neonates obtained in
      autumn by dissection with neonates born naturally in the spring. Our results
      demonstrate that deferral of parturition until spring represents a trade-off
      between key offspring characteristics (spring neonates exhibit lower growth
      rates, reduced sprint speed after birth, reduced condition and decreased energy
      reserves) and offspring size [spring neonates are heavier (wet mass) and longer
      (snout-vent length)]. Furthermore, when females are placed into cold experimental
      conditions in spring around the time of natural parturition, this species is able
      to defer parturition for an additional 4 weeks with no significant effect on
      offspring characteristics. Our results provide further evidence that flexibility
      in birth date provides a significant advantage to viviparous lizards living in
      cold climates.

PMID- 17525955
TI  - Analysis of DRD4 and DAT polymorphisms and behavioral inhibition in healthy
      adults: implications for impulsivity.
AB  - Impulsivity, a highly prevalent symptom in multiple psychiatric disorders, is a
      partially heritable trait influenced by specific biological mechanisms. In
      particular, dopamine is proposed to play a role in impulsive behaviors and recent
      studies have implicated functional polymorphisms of dopamine-related genes in
      impulsive behaviors across different clinical and behavioral classifications.
      However, most have not isolated the impulsivity construct per se as a
      biologically based and measurable endophenotype. The present study was therefore
      undertaken in a sample of healthy adults to investigate the influence of two
      candidate dopaminergic gene polymorphisms (DRD4 and DAT) on the endophenotype of
      impulsivity, which we operationalized as behavioral inhibition during the Stop
      signal task. We recruited an ethnically diverse sample of 119 healthy adults to
      complete a self-report questionnaire of impulsivity and to perform a Stop-signal
      task. We report significant differences in inhibitory control between individuals
      with at least one 7-repeat allele of the DRD4 polymorphism, as well as an
      interaction between DRD4 and DAT genotypes, on inhibitory control. Results of the
      present study support the influence of dopaminergic variation on impulsive
      related measures, as well as the advantage of using measures which are likely
      more sensitive to the effects of such genetic variation.

PMID- 17525956
TI  - Hidden drugs, hidden risks--is cocaine use a new risk factor for stent
      thrombosis?

PMID- 17525957
TI  - Blood loss during percutaneous coronary intervention: tedious or important?

PMID- 17525958
TI  - Stent fracture-unusual cause of DES restenosis.

PMID- 17525959
TI  - Alcohol septal ablation after failed surgical myectomy.
AB  - We describe the case of a successful alcohol septal ablation in a patient with
      persistent gradient and severe symptoms postsurgical myectomy. The alcohol
      ablation of the thickened septum abolished the left ventricular outflow gradient
      and the systolic anterior motion (SAM) of the mitral valve. Although the surgical
      literature advocates for mitral valve replacement in patients who continue to
      have SAM with significant outflow obstruction postmyectomy, targeted alcohol
      septal ablation of the remaining septum appears to be an attractive alternative.

PMID- 17525960
TI  - New approach to septal ablation: glue (cyanoacrylate) septal ablation.
AB  - Alcohol septal ablation is an alternative way of treatment in hypertrophic
      obstructive cardiomyopathy patients who are refractory to medical treatment. This
      case report describes a new way of septal ablation with glue (cyanoacrylate) in a
      HOCM patient who has extensive collateral to posterior descending coronary artery
      which precludes alcohol ablation.

PMID- 17525961
TI  - Filters: not ready for prime time.

PMID- 17525963
TI  - Is survival of patients with atherosclerotic renal artery stenosis affected by
      different predictors compared to other atherosclerosis manifestations?

PMID- 17525962
TI  - Factors affecting long-term survival following renal artery stenting.
AB  - INTRODUCTION: This study defines clinical variables at the time of renal artery
      stenting that may be predictors of long-term all-cause mortality. METHODS: The
      data are derived from the single operator, single center, renal stent
      retrospective study (SOCRATES) and includes a review of 748 (336 men, 412 women)
      consecutive symptomatic patients with de novo atherosclerotic renal artery
      stenosis treated over an 11-year period. All patients had clinical indications
      for renal revascularization, including, but not limited to; suboptimal control of
      hypertension, chronic kidney disease, and cardiac disturbance syndromes. Clinical
      variables at the time of the index procedure were evaluated as predictors of all
      cause mortality using multivariate analysis. Mortality data were derived from
      hospital records and formal queries of the State Department of Health and Human
      Services, Health and Vital Statistics Division database. RESULTS: In-hospital, 30
      day and 6-month mortality rates were 0.5, 2.0, and 6.3%, respectively. Overall
      patient survival at years 1, 5, and 10 was 91.2, 66.6, and 40.9%, respectively.
      Comorbid conditions, including chronic obstructive pulmonary disease and
      congestive heart failure, were independently associated with increased mortality.
      There were incremental changes in mortality in patients with baseline azotemia,
      [preprocedure serum creatinine (sCr) 1.5-2.09 mg/dL hazard ratio 1.52; sCr >2.5
      mg/dL hazard ratio 3.39]. Therapy with lipid lowering agents offered a survival
      advantage (hazard ratio 0.69, P = 0.0.049); however, this study was not designed
      to evaluate a "protective effect" of lipid lowering medications. CONCLUSIONS:
      Patients with chronic obstructive pulmonary disease and congestive heart failure
      undergoing renal artery stent revascularization have a poor long-term prognosis.
      Baseline azotemia is the strongest independent predictor of all cause mortality,
      with more than 70% of patients with marked azotemia (sCr >2.5) dead at 5 years.

PMID- 17525964
TI  - Survival in atherosclerotic renal artery stenosis: its all about renal function,
      or is it?

PMID- 17525965
TI  - Percutaneous mitral valve annuloplasty for ischemic mitral regurgitation: first
      in man experience with a temporary implant.
AB  - OBJECTIVE: This study evaluated human feasibility and acute efficacy of a novel
      percutaneous transvenous mitral annuloplasty (PTMA) device (Viacor) placed
      temporarily in the coronary sinus (CS): the implant allows in-situ incremental
      adjustment to optimally reduce the anterior-posterior mitral annulus (MA)
      dimension, and improve leaflet co-aptation and reducing mitral regurgitation
      (MR). BACKGROUND: Surgical annuloplasty remains the standard treatment of severe
      ischemic MR but its application is limited by high morbidity and mortality. The
      effectiveness of PTMA device (Viacor) to reduce MR in the short-term has been
      demonstrated in animals studies but not in humans. METHODS: Symptomatic patients
      with ischemic MR graded 2+ to 4+ requiring surgical mitral annuloplasty were
      screened. Patients with any mitral leaflet or mitral apparatus abnormality were
      excluded. Preoperatively, under general anesthesia and transesophageal
      echocardiography guidance, a temporary PTMA device was placed via the right
      internal jugular or subclavian vein. RESULTS: Four patients were studied. After
      device placement and adjustment, regurgitant volume was substantially reduced
      (45.5 +/- 24.4 to 13.3 +/- 7.3 ml) via MA anterior-posterior diameter reduction
      (40.75 +/- 4.3 to 35.2 +/- 1.6 mm) in 3 patients. In one patient, the PTMA device
      could not be deployed due to extreme angulated anatomy. CONCLUSIONS: PTMA in
      human is feasible and reduces ischemic MR (to grade 1+) by reducing MA anterior
      posterior diameter. Temporary placement of the PTMA device may assist in the
      development of permanent implants and ensure optimal efficacy.

PMID- 17525966
TI  - Percutaneous mitral annuloplasty: not always a cinch.

PMID- 17525967
TI  - Overview of the 2006 Food and Drug Administration Circulatory System Devices
      Panel meeting on drug-eluting stent thrombosis.
AB  - Drug-eluting stents (DES) seemed likely to mitigate the problem of restenosis and
      have become the predominant stent deployed during percutaneous coronary
      intervention (PCI). Sustained concerns about the rate of stent thrombosis (ST),
      particularly very late ST (>1 year following PCI) led to a meeting of the
      Circulatory System Devices Advisory Panel to address "on-label" and "off-label"
      use as well as appropriate duration of dual antiplatelet therapy following DES.
      Over 40 presentations by members of the FDA, industry personnel, and leaders in
      the field of interventional cardiology helped set forth the body of data
      available on DES. Standardized definitions of ST created by the Academic Research
      Consortium were applied to existing randomized trials and registries. At the end
      of the 2-day session, the consensus of the panel was that "on-label" DES use is
      not associated with increased incidence of death and myocardial infarction (MI),
      although it is associated with increased rates of very late ST. "Off-label" use
      is associated with increased risk of death or MI when compared with "on-label"
      use. Insufficient data exist to determine the duration of clopidogrel that would
      minimize ST and bleeding risk, but the panel agreed with the current ACC/AHA/SCAI
      guidelines regarding dual antiplatelet therapy for at least 12 months in patients
      at low risk for bleeding, especially with "off-label" use. More data from trials
      designed with better control arms and prespecified analyses of complex patients
      and lesions subsets over longer periods of follow-up are needed.

PMID- 17525968
TI  - Ultrasound-guided core-needle biopsy in the diagnosis of head and neck masses:
      indications, technique, and results.
AB  - BACKGROUND: Unclear cervicofacial masses are common presentations that often
      require tissue sampling to guide therapy. While open biopsy is invasive, fine
      needle aspiration cytology includes a high rate of nondiagnostic samples.
      METHODS: A retrospective analysis on 181 core-needle biopsies in 88 patients was
      performed to determine the diagnostic efficacy of ultrasound-guided core-needle
      biopsies in the head and neck. RESULTS: We experienced 100% success in obtaining
      high-quality histopathologic specimens. The target tissue was correctly sampled
      in 80 of 88 patients. In these patients the sensitivity, specificity, and
      accuracy rate of core-needle biopsies in differentiating benign from malignant
      cervicofacial lesions was 98.1%, 100%, and 98.8%, respectively. CONCLUSIONS:
      Ultrasound-guided core-needle biopsies can be recommended as a safe and reliable
      technique in the diagnosis of cervicofacial masses with a high diagnostic yield.
      It obtains tissue samples of high quality and represents a sufficient alternative
      to open biopsy even in the diagnosis of lymphoma.

PMID- 17525969
TI  - Is galectin-3 a good method for the detection of malignancy in patients with
      thyroid nodules and a cytologic diagnosis of "follicular neoplasm"? A critical
      appraisal of the evidence.
AB  - BACKGROUND: Thyroid nodules are the most common surgical disease of the thyroid.
      Fine-needle aspiration biopsy (FNAB) is the most commonly employed tool for
      establishing a diagnosis. However, 15% to 25% of FNAB reports yield inconclusive
      results. Immunostaining of cytological smears from FNAB with galectin-3 has been
      proposed as a tool for differentiating between benign and malignant nodules. We
      performed a systematic review to evaluate the utility of galectin-3. METHODS:
      Prospective studies of nodules with FNAB reports of "follicular neoplasm" and
      with a definitive diagnosis confirmed by histopathology were selected.
      Calculations of individual sensitivity, specificity, and positive and negative
      likelihood ratios were made. RESULTS: The articles selected were those with the
      best methodological quality. CONCLUSION: Galectin-3 could be a good tool to guide
      therapeutic decision in patients with thyroid nodules and FNAB results of
      follicular neoplasm, but available information has methodological flaws that
      precludes a definitive answer about galectin-3 utility in the clinical setting.

PMID- 17525970
TI  - Introduction of lymphangiography and percutaneous embolization of the thoracic
      duct in a stepwise approach to the management of chylous fistulas.
AB  - BACKGROUND: Chylous fistula occurring after head and neck or thoracic surgery is
      an uncommon but well-described complication, with a reported incidence of 1% to
      2.5%. Conservative management can be successful and consists of dietary measures
      combined with suction drainage. This article reports on percutaneous embolization
      of the thoracic duct through catheterization of the retroperitoneal lymph
      vessels. METHODS: Two patients, in whom conservative management for cervical
      chylous fistula failed, underwent lymphangiography with opacification of the
      thoracic duct, followed by radioguided catheterization and embolization. RESULTS:
      Embolization was successful in both patients. In 1 patient the procedure had to
      be repeated once to stop the chylous drainage. CONCLUSIONS: Radioguided
      percutaneous catheterization and embolization of the retroperitoneal lymph
      vessels offers an excellent treatment option for patients with persistent chylous
      fistulas after failure of conservative management. We revised our stepwise
      management protocol (de Gier, Head Neck 1996; 18:347-351) and now consider this
      procedure as the secondary intervention step.

PMID- 17525971
TI  - Immune reconstitution inflammatory syndrome in cancer patients with pulmonary
      aspergillosis recovering from neutropenia: Proof of principle, description, and
      clinical and research implications.
AB  - BACKGROUND: Assessing the outcome of patients with invasive pulmonary
      aspergillosis by using conventional criteria is difficult, particularly when
      clinical and radiologic worsening coincides with neutrophil recovery. Usually, it
      is assumed that this deterioration is related to progressive aspergillosis,
      prompting changes in patient management. However, its temporal relation with
      neutrophil recovery suggests that it may be caused by an immune reconstitution
      syndrome (IRIS). Galactomannan is an Aspergillus-specific polysaccharide that is
      released during aspergillosis and is detected by the serum galactomannan test,
      which has been approved by the United States Food and Drug Administration for the
      diagnosis of invasive aspergillosis. In this study, the authors used sequential
      galactomannan testing to distinguish IRIS responses from progressive
      aspergillosis. METHODS: From April 2001 to December 2006, patients with
      hematologic malignancies underwent galactomannan screening during periods when
      they were at risk. The clinical and laboratory findings from patients who had
      >or=2 consecutive positive galactomannan assays (optical density, >or=0.5) were
      reviewed. RESULTS: Nineteen neutropenic patients with aspergillosis developed
      clinical and radiologic pulmonary deterioration during neutrophil recovery.
      Deterioration coincided with microbiologic response, as documented by rapid
      normalization of serum galactomannan, and, in 16 patients, was followed by
      complete clinical response and survival at 3 months, although there were no
      changes in antifungal therapy. The 3 patients who died during the first month had
      no evidence of aspergillosis at autopsy examination. CONCLUSIONS: The authors
      propose that IRIS was responsible for the current findings and provide a
      definition for the syndrome. They also recommend serial galactomannan testing to
      guide aspergillosis management. Declining galactomannan values imply IRIS with an
      aspergillus response and obviate the need for invasive procedures and alternative
      antifungal therapies, whereas persistent galactomannan elevation indicates
      progressive aspergillosis and requires prompt treatment modification.

PMID- 17525972
TI  - Familiality and diagnostic patterns of subphenotypes in the National Institutes
      of Mental Health bipolar sample.
AB  - Bipolar-related subphenotypes that cluster within families may help identify
      subsets of patients that are more genetically homogeneous. Environmental or
      assessment factors that segregate by family may influence estimates of
      familiality. We aimed to determine familiality of subphenotypes of bipolar
      disorder (BP), accounting for effects of age, sex, diagnosis, and site/wave of
      ascertainment. We studied 589 sibships with 1416 siblings affected with bipolar I
      (BPI), schizoaffective disorder, bipolar type (SAB), bipolar II (BPII), or
      recurrent unipolar depression (RUDD). Sibships were from families with > or =2
      BPI cases collected by the NIMH Bipolar Genetics Initiative (NIMHBGI). Rapid
      cycling showed the strongest evidence for familiality [odds ratio (OR) (95%CI) =
      2.02 (1.43, 2.85), P = 6.0 x 10(-5)] in a model including age, sex, diagnosis,
      and site/wave of ascertainment. Additional significantly familial traits were
      comorbid alcohol abuse/dependence (P = 2 x 10(-4)) and comorbid panic disorder (P
      = 8 x 10(-3)), as well as psychosis, suicidal thoughts, and rapid mood switching
      (P = 6 x 10(-3) - 0.03). Omission of the effect of site/wave of ascertainment
      from the model inflated the significance level of the apparent familial
      association of almost all subphenotypes from one to four orders of magnitude. We
      have found evidence of familiality for subphenotypes of BP. In multicenter
      samples, familiality may be overestimated if variability in diagnosis of
      subphenotypes between site/wave of ascertainment is not considered.

PMID- 17525973
TI  - Meta-analyses suggest association between COMT, but not HTR1B, alleles, and
      suicidal behavior.
AB  - Several studies have suggested that suicidal behavior is at least partially
      determined by genetic factors, supporting a search for related genes. Two genes
      that have been highlighted in the literature as being involved are HTR1B, which
      codes for the serotonin 1B receptor, and COMT, which is related to the
      inactivation of catecholamines. In order to assess the combined evidence for the
      numerous studies that have been published relating suicidal behavior to these two
      genes, two different random effects meta-analyses were conducted utilizing seven
      studies related to HTR1B and six studies related to COMT. For HTR1B, the combined
      evidence from 789 case and 1,247 control subjects/participants, suggested that
      there was no significant association between the HTR1B G861C polymorphism and
      suicidal behavior. For COMT, based on the combined data from 519 cases and 933
      control subjects, there was evidence of a significant association between the
      COMT 158Met polymorphism and suicidal behavior. Although the results for COMT
      were not influenced by publication bias, the significance of the combined results
      was not robust and was related to the gender of the case and control subjects.
      The results for COMT support past literature that has found a relationship
      between suicidal behavior and COMT, and has also found that the relationship
      differs for males and females. Given that in the United States a higher
      proportion of females attempt suicide, and the higher proportion of males
      successfully commit suicide, it is possible that COMT is related to the lethality
      of suicide attempts.

PMID- 17525974
TI  - Evidence that the COMT(Val158Met) polymorphism moderates sensitivity to stress in
      psychosis: an experience-sampling study.
AB  - Gene-environment interactions involving the catechol-O-methyltransferase
      Val(158)Met polymorphism (COMT(Val158Met)) have been implicated in the causation
      of psychosis. Evidence from general population studies suggests that Met/Met
      subjects are sensitive to stress, a trait associated with psychosis. We
      hypothesized that the Met allele would moderate the effects of stress on negative
      affect (NA) in controls, and on NA and psychosis in patients with a psychotic
      disorder. Thirty-one patients with a psychotic disorder and comorbid cannabis
      misuse and 25 healthy cannabis users were studied with the experience sampling
      method (ESM), a structured diary technique assessing current context and
      emotional and psychotic experiences in daily life. A significant interaction
      between COMT(Val158Met) genotype and ESM stress in the model of NA was found for
      patients (interaction chi(2) = 7.4, P = 0.02), but not for controls (interaction
      chi(2) = 3.8, P = 0.15). In the model of ESM psychosis, a significant interaction
      between COMT(Val158Met) genotype and ESM stress was also apparent (interaction
      chi(2) = 11.6, P < 0.01), with Met/Met patients showing the largest increase in
      psychotic experiences as well as NA in reaction to ESM stress. The findings
      suggest that the COMT(Val158Met) polymorphism moderates affective and psychotic
      responses to stress in patients with psychosis, providing evidence for gene
      environment interaction mechanisms in the formation of psychotic symptoms.

PMID- 17525975
TI  - Differential dopamine receptor D4 allele association with ADHD dependent of
      proband season of birth.
AB  - Season of birth (SOB) has been associated with attention deficit hyperactivity
      disorder (ADHD) in two existing studies. One further study reported an
      interaction between SOB and genotypes of the dopamine D4 receptor (DRD4) gene. It
      is important that these findings are further investigated to confirm or refute
      the findings. In this study, we investigated the SOB association with ADHD in
      four independent samples collected for molecular genetic studies of ADHD and
      found a small but significant increase in summer births compared to a large
      population control dataset. We also observed a significant association with the 7
      repeat allele of the DRD4 gene variable number tandem repeat polymorphism in exon
      three with probands born in the winter season, with no significant differential
      transmission of this allele between summer and winter seasons. Preferential
      transmission of the 2-repeat allele to ADHD probands occurred in those who were
      born during the summer season, but did not surpass significance for association,
      even though the difference in transmission between the two seasons was nominally
      significant. However, following adjustment for multiple testing of alleles none
      of the SOB effects remained significant. We conclude that the DRD4 7-repeat
      allele is associated with ADHD but there is no association or interaction with
      SOB for increased risk for ADHD. Our findings suggest that we can refute a
      possible effect of SOB for ADHD.

PMID- 17525976
TI  - Prediction of psychosis onset in Alzheimer disease: the role of depression
      symptom severity and the HTR2A T102C polymorphism.
AB  - Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable phenotype
      associated with a more severe course. We recently found an association of AD + P
      with depression symptom severity. Reports have shown an association of a
      serotonin-2A receptor (HTR2A) gene T102C polymorphism with AD + P and with
      depression during AD. We examined the interaction of this common genetic
      polymorphism with depression and increased psychosis risk. Subjects with possible
      or probable AD or mild cognitive impairment (MCI) without psychosis at study
      entry were genotyped for the HTR2A T102C polymorphism and reassessed every 6
      months until psychosis onset. Psychotic and depressive symptoms were rated using
      the CERAD behavioral rating scale (CBRS). Cox proportional hazard models with
      time-dependent covariates were used to examine associations with psychosis onset.
      A total of 324 Caucasian subjects completed at least one follow-up exam.
      Depressive symptom severity was a strong predictor of psychosis onset. Neither
      psychosis onset nor depression severity was associated with the HTR2A genotype.
      Genotype interacted with depression severity to moderate the risk of AD + P
      onset. This did not result from an interaction of HTR2A genotype with
      antidepressant use. Psychosis onset in AD is strongly associated with severity of
      depressive symptoms, an association that may be modified by HTR2A genotype.

PMID- 17525977
TI  - Candidate gene analysis of 21q22: support for S100B as a susceptibility gene for
      bipolar affective disorder with psychosis.
AB  - A genome-wide scan in 60 bipolar affective disorder (BPAD) affected sib-pairs
      (ASPs) identified linkage on chromosome 21 at 21q22 (D21S1446, NPL = 1.42, P =
      0.08), a BPAD susceptibility locus supported by multiple studies. Although this
      linkage only approaches significance, the peak marker is located 12 Kb upstream
      of S100B, a neurotrophic factor implicated in the pathology of psychiatric
      disorders, including BPAD and schizophrenia. We hypothesized that the linkage
      signal at 21q22 may result from pathogenic disease variants within S100B and
      performed an association analysis of this gene in a collection of 125 BPAD type I
      trios. S100B single nucleotide polymorphisms (SNPs) rs2839350 (P = 0.022) and
      rs3788266 (P = 0.031) were significantly associated with BPAD. Since variants
      within S100B have also been associated with schizophrenia susceptibility, we
      reanalyzed the data in trios with a history of psychosis, a phenotype in common
      between the two disorders. SNPs rs2339350 (P = 0.016) and rs3788266 (P = 0.009)
      were more significantly associated in the psychotic subset. Increased
      significance was also obtained at the haplotype level. Interestingly, SNP
      rs3788266 is located within a consensus-binding site for Six-family transcription
      factors suggesting that this variant may directly affect S100B gene expression.
      Fine-mapping analyses of 21q22 have previously identified transient receptor
      potential gene melastatin 2 (TRPM2), which is 2 Mb upstream of S100B, as a
      possible BPAD susceptibility gene at 21q22. We also performed a family-based
      association analysis of TRPM2 which did not reveal any evidence for association
      of this gene with BPAD. Overall, our findings suggest that variants within the
      S100B gene predispose to a psychotic subtype of BPAD, possibly via alteration of
      gene expression.

PMID- 17525978
TI  - The importance of genetic counseling for individuals with schizophrenia and their
      relatives: potential clients' opinions and experiences.
AB  - Genetic counseling is a health service, which has been indicated for individuals
      with psychiatric conditions in their families. However, little is known about the
      awareness and/or experiences of genetic counseling of this group. This study was
      designed to assess the awareness and perceptions of genetic counseling among
      individuals affected by schizophrenia and their relatives. Data was collected via
      two online surveys. Study participants either had schizophrenia or had a relative
      with schizophrenia and were recruited via links from schizophrenia web sites.
      This study was granted IRB approval. Sixty-eight individuals with schizophrenia
      and 145 relatives completed the surveys. Ninety-four percent of all respondents
      had not been offered genetic counseling. Zero percent of affected individuals and
      only 5% of relatives had received genetic counseling. Forty-four percent of
      affected individuals and 41% of relatives indicated that their family planning
      decisions were influenced by the presence of schizophrenia in their family.
      Seventy four percent of relatives and 72% of people with schizophrenia thought
      genetic counseling would be useful to them. Respondents indicated that they felt
      genetic counseling would be useful for them and that they would like to see a
      genetic counselor. However, few individuals are being offered genetic counseling
      services. The awareness of genetic counseling needs to be raised among physicians
      and families affected by schizophrenia.

PMID- 17525979
TI  - Activation of Matrix Metalloproteinase-3 is altered at the frog neuromuscular
      junction following changes in synaptic activity.
AB  - The extracellular matrix surrounding the neuromuscular junction is a highly
      specialized and dynamic structure. Matrix Metalloproteinases are enzymes that
      sculpt the extracellular matrix. Since synaptic activity is critical to the
      structure and function of this synapse, we investigated whether changes in
      synaptic activity levels could alter the activity of Matrix Metalloproteinases at
      the neuromuscular junction. In particular, we focused on Matrix Metalloproteinase
      3 (MMP3), since antibodies to MMP3 recognize molecules at the frog neuromuscular
      junction, and MMP3 cleaves a number of synaptic basal lamina molecules, including
      agrin. Here we show that the fluorogenic compound (M2300) can be used to perform
      in vivo proteolytic imaging of the frog neuromuscular junction to directly
      measure the activity state of MMP3. Application of this compound reveals that
      active MMP3 is concentrated at the normal frog neuromuscular junction, and is
      tightly associated with the terminal Schwann cell. Blocking presynaptic activity
      via denervation, or TTX nerve blockade, results in a decreased level of active
      MMP3 at the neuromuscular junction. The loss of active MMP3 at the neuromuscular
      junction in denervated muscles can result from decreased activation of pro-MMP3,
      or it could result from increased inhibition of MMP3. These results support the
      hypothesis that changes in synaptic activity can alter the level of active MMP3
      at the neuromuscular junction.

PMID- 17525981
TI  - Accessing the mental space-Spatial working memory processes for language and
      vision overlap in precuneus.
AB  - The "overlapping systems" theory of language function argues that linguistic
      meaning construction crucially relies on contextual information provided by
      "nonlinguistic" cognitive systems, such as perception and memory. This study
      examines whether linguistic processing of spatial relations established by
      reading sentences call on the same posterior parietal neural system involved in
      processing spatial relations set up through visual input. Subjects read simple
      sentences, which presented two agents in relation to each other, and were
      subsequently asked to evaluate spatial (e.g., "Was he turned towards her?") and
      equally concrete nonspatial content (e.g., "Was he older than her?"). We found
      that recall of the spatial content relative to the nonspatial content resulted in
      higher BOLD response in a dorsoposterior network of brain regions, most
      significantly in precuneus, strikingly overlapping a network previously shown to
      be involved in recall of spatial aspects of images depicting similar scenarios.
      This supports a neurocognitive model of language function, where sentences
      establish meaning by interacting with the perceptual and working memory networks
      of the brain.

PMID- 17525980
TI  - Altered functional connectivity of primary visual cortex in early blindness.
AB  - In early blindness, the primary visual area (PVA) loses the ability to process
      visual information, and shifts to working on the processing of somatosensory
      input, auditory input, and some higher-level cognitive functions. It has not yet
      been investigated whether such functional changes can lead to alterations of the
      functional connectivity between the PVA and other brain areas in resting state.
      The purpose of this study is to investigate the differences in the functional
      connectivity of the PVA between early blind and sighted subjects using resting
      functional MRI data. The altered functional connectivity was identified by
      comparing the correlation coefficients of the PVA with other brain areas between
      16 early blind subjects (blindness onset within 1 year of age) and 32 gender- and
      age-matched healthy sighted volunteers. Compared with the sighted, the early
      blind subjects showed decreased functional connectivity between the left PVA and
      the bilateral supplementary motor area (SMA), pre- and postcentral gyri, superior
      parietal lobule, and the left superior and middle temporal gyri. Early blind
      subjects also showed decreased functional connectivity between the right PVA and
      the bilateral SMA, pre- and postcentral gyri. Our findings suggest that early
      deprivation of a single sensory modality induces alterations of functional
      connectivity between the deprived functional area and other associated brain
      areas.

PMID- 17525982
TI  - Cortical topography of human first dorsal interroseus during individuated and
      nonindividuated grip tasks.
AB  - Neural activity in the motor cortex and its descending projections is modulated
      in a task-related manner. Several TMS studies have shown that when normal human
      subjects execute different manual tasks requiring similar contraction levels in
      first dorsal interroseous (FDI) there is a task-related modulation of the
      amplitude of FDI motor evoked potentials (MEPs). Not all studies of task-related
      changes show the same pattern of results, however. One reason for this might be
      methodological. Studies have assessed task-related changes by stimulating a
      single site, which can provide information about task-related changes in the
      excitability of the cortex at that site, but which is not sensitive to
      excitability changes throughout the muscle's cortical representation. We
      investigated how the execution of an individuated versus a nonindividuated
      isometric grasping task affected the excitability of FDI's entire cortical
      representation. We examined FDI MEP amplitudes while subjects grasped an object
      between their thumb and index finger, or when they grasped the same object
      between their thumb and all four fingers, keeping the background level of EMG in
      FDI constant for the two tasks. We found no overall task-related change in the
      excitability of FDI or its cortical topography, possibly due to behavioral
      differences of individual subjects. The stability of FDI's cortical
      representation during two different manual tasks expands the possibilities for
      studying cortical reorganization in the context of active muscle contraction,
      which will enable us to better understand whether changes in the motor system
      observed when muscles are at rest are also present during voluntary muscle
      recruitment.

PMID- 17525983
TI  - Imaging mesial temporal lobe activation during scene encoding: comparison of fMRI
      using BOLD and arterial spin labeling.
AB  - Memory encoding is a critical brain function subserved by the hippocampus (HP)
      and mesial temporal lobe (mTL) structures. Visualization of mTL memory activation
      with BOLD fMRI is complicated by the presence of static susceptibility gradients
      in this region. Arterial spin labeled (ASL) perfusion fMRI offers an alternative
      approach not dependent on susceptibility contrast that instead suffers from lower
      intrinsic signal-to-noise ratio. An improved ASL perfusion fMRI approach
      combining pseudo-continuous ASL and a T(2)*-insensitive sequence (GRASE) with
      background suppression was compared to BOLD fMRI at 3 T during a scene encoding
      task known to activate the HP. Overall, an approximate sixfold sensitivity
      increase of ASL fMRI was achieved, with improved coverage in the anterior mTL,
      while suppression of the static tissue enhanced the stability of the ASL series
      by a factor of 2.4. Perfusion fMRI using this approach with 4 mm isotropic
      resolution yielded better localized and stronger group activation maps than BOLD
      fMRI at a standard resolution of 3 mm isotropic voxels. Increasing the resolution
      for BOLD to 2.5 mm isotropic produced stronger mTL and hippocampal activation in
      the group and individual subjects than the ASL technique, due to superior
      temporal resolution and reduced partial volume effects. Future improvements in
      ASL spatial and temporal resolution would allow the benefits of both approaches
      to be combined to further enhance the sensitivity for detecting mTL activation
      during memory encoding.

PMID- 17525984
TI  - Enhanced amygdala and medial prefrontal activation during nonconscious processing
      of fear in posttraumatic stress disorder: an fMRI study.
AB  - Biological models of posttraumatic stress disorder (PTSD) suggest that patients
      will display heightened amygdala but decreased medial prefrontal activity during
      processing of fear stimuli. However, a rapid and automatic alerting mechanism for
      responding to nonconscious signals of fear suggests that PTSD may display
      heightened rather than decreased MPFC under nonconscious processing of fear
      stimuli. This study used functional magnetic resonance imaging to examine blood
      oxygenation level-dependent signal changes during nonconscious presentation (16.7
      ms, masked) of fearful and neutral faces in 15 participants with PTSD and 15 age
      and sex-matched healthy control participants. Results indicate that PTSD
      participants display increased amygdala and MPFC activity during nonconscious
      processing of fearful faces. These data extend existing models by suggesting that
      the impaired MPFC activation in PTSD may be limited to conscious fear processing.
      Hum Brain Mapp, 2008. (c) 2007 Wiley-Liss, Inc.

PMID- 17525985
TI  - Cortical thinning in obsessive compulsive disorder.
AB  - Although studies of obsessive-compulsive disorder (OCD) over the last 20 years
      have suggested abnormalities in frontal-subcortical circuitry, evidences of
      structural abnormalities in those areas are still imperfect and contradictory.
      With recent advances in neuroimaging technology, it is now possible to study
      cortical thickness based on cortical surfaces, which offers a direct quantitative
      index of cortical mass. Using the constrained Laplacian-based automated
      segmentation with proximities (CLASP) algorithm, we measured cortical thickness
      of 55 patients with OCD (33 men and 22 women) and 52 age- and sex-matched healthy
      volunteers (32 men and 20 women). We found multiple regions of cortical thinning
      in OCD patients compared to the normal control group. Patients with OCD had
      thinner left inferior frontal, left middle frontal, left precentral, left
      superior temporal, left parahippocampal, left orbitofrontal, and left lingual
      cortices. Most thinned regions were located in the left ventral cortex system,
      providing a new perspective that this ventral cortical system may be involved in
      the pathophysiology of OCD.

PMID- 17525986
TI  - Hemodynamic response to visual stimulation in newborn infants using functional
      near-infrared spectroscopy.
AB  - Brain activity is associated with physiological changes, which alter the optical
      properties of tissue. These changes can be detected by near-infrared spectroscopy
      (NIRS). Aim of the study was to determine changes in cerebral oxygenation in
      response to stimulation in the visual cortex in newborn infants during
      spontaneous sleep in the first days of life. We used an in-house developed
      multichannel NIRS imaging instrument, the MCP-II, to measure changes in
      concentration of oxyhemoglobin (O(2)Hb) and deoxyhemoglobin (HHb) in specific
      brain areas. In 10 out of 15 subjects, a significant increase in O(2)Hb and/or a
      significant decrease in HHb were found in one or more channels over the occipital
      cortex. During stimulation, O(2)Hb increased by a mean of 0.98 mumol/l, HHb
      decreased by a mean 0.17 mumol/l, and total-Hb increased by a mean of 0.81
      mumol/l. The hemodynamic response to visual stimulation in the occipital cortex
      in newborn infants is similar to adults. The increase in O(2)Hb and the
      simultaneous decrease in HHb during stimulation suggest an increase in cerebral
      blood flow (CBF) that overcompensates for the increased oxygen consumption
      (CMRO(2)) in the activated cortical area.

PMID- 17525987
TI  - An fMRI study of prefrontal brain activation during multiple tasks in patients
      with major depressive disorder.
AB  - OBJECTIVE: Previous research has provided conflicting information regarding the
      pattern of brain activation associated with cognitive performance in depressed
      people. We aimed to assess brain activation related to cognitive performance
      during planning and working memory tasks. METHOD: fMRI scans were conducted using
      a modified Tower of London task and a 2-back task in 13 patients with major
      depressive disorder and a matched control group. RESULTS: Task performance was
      impaired in the depressed group on the Tower of London task but there were no
      differences between the groups in task performance on the n-back task. The
      patient group showed widespread increased brain activation in both tasks. There
      was considerable overlap in increased activation between the two tasks,
      especially in right prefrontal cortical regions. CONCLUSIONS: Patients with
      depression exhibit increased brain activation, especially in right prefrontal
      regions, across several types of cognitive task activity. Patients with
      depression may recruit greater brain regions to achieve similar or even poorer
      task performance than control subjects.

PMID- 17525988
TI  - Surface-based morphometry of the anterior cingulate cortex in first episode
      schizophrenia.
AB  - The anterior cingulate cortex (ACC) appears to be critically involved in the
      pathophysiology of schizophrenia, but past attempts at characterizing
      pathological changes in the region using magnetic resonance imaging have been
      restricted by a limited appreciation of its functional and anatomical diversity
      and a reliance on relatively coarse metrics (e.g., volume) to index anatomical
      change. In this study, we applied a novel, surface-based protocol to T1-weighted
      scans acquired from 40 first episode schizophrenia patients and 40 healthy
      controls individually matched for age, sex, and morphology of the paracingulate
      sulcus, a major anatomical variation that has been shown to affect morphometric
      estimates in the region. The surface-based approach enabled calculation of
      regional grey matter volume, surface area and curvature, cortical thickness, and
      depth of the cingulate sulcus, with sub-millimeter precision. Relative to
      controls, schizophrenia patients displayed a bilateral reduction in thickness of
      paralimbic regions of the ACC, along with a concomitant increase in surface area
      of both the limbic and paralimbic ACC. No differences were identified for
      regional grey matter volume, surface curvature, or CS depth. These findings
      illustrate the advantages of moving beyond traditional volume-based approaches
      when investigating cortical morphometry, and indicate that the early stages of
      schizophrenia are associated with a specific pattern of ACC abnormalities that
      cannot be attributed to variations in sulcal and gyral morphology.

PMID- 17525989
TI  - nAChR-mediated calcium responses and plasticity in Drosophila Kenyon cells.
AB  - In Drosophila, nicotinic acetylcholine receptors (nAChRs) mediate fast excitatory
      synaptic transmission in mushroom body Kenyon cells, a neuronal population
      involved in generation of complex behaviors, including responses to drugs of
      abuse. To determine whether activation of nAChRs can induce cellular changes that
      contribute to functional plasticity in these neurons, we examined nicotine-evoked
      responses in cells cultured from brains of late stage OK107-GAL4 pupae. Kenyon
      cells can be identified by expression of green fluorescent protein (GFP+).
      Nicotine activates alpha-bungarotoxin-sensitive nAChRs, causing a rapid increase
      in intracellular calcium levels in over 95% of the Kenyon cells. The nicotine
      evoked calcium increase has a voltage-gated calcium channel (VGCC) dependent
      component and a VGCC-independent component that involves calcium influx directly
      through nAChRs. Thapsigargin treatment reduces the nicotine response consistent
      with amplification by calcium release from intracellular stores. The response to
      nicotine is experience-dependent: a short conditioning pulse of nicotine causes a
      transient 50% reduction in the magnitude of the response to a test pulse of
      nicotine when the interpulse interval is 4 h. This cellular plasticity is
      dependent on activation of the VGCC-component of the nicotine response and on
      cAMP-signaling, but not on protein synthesis. These data demonstrate that
      activation of nAChRs induces a calcium-dependent plasticity in Kenyon cells that
      could contribute to adult behaviors involving information processing in the
      mushroom bodies including responses to nicotine.

PMID- 17525990
TI  - Effects of GABA and GABA receptor inhibition on differentiation of mesencephalic
      precursors into dopaminergic neurons in vitro.
AB  - Neurotransmitters have been shown to control CNS neurogenesis, and GABA-mediated
      signaling is thought to be involved in the regulation of nearly all key
      developmental stages. Generation of dopaminergic (DA) neurons from stem/precursor
      cells for cell therapy in Parkinson's disease has become a major focus of
      research. However, the possible effects of GABA on generation of DA neurons from
      proliferating neurospheres of mesencephalic precursors have not been studied. In
      the present study, GABA(A), and GABA(B) receptors were found to be located in DA
      cells. Treatment of cultures with GABA did not cause significant changes in
      generation of DA cells from precursors. However, treatment with the GABA(A)
      receptor antagonist bicuculline (10(-5) M) led to a significant increase in the
      number DA cells, and treatment with the GABA(B) receptor antagonist CGP 55845
      (10(-5) M) to a significant decrease. Simultaneous treatment with bicuculline and
      CGP 55845 did not induce significant changes. Apoptotic cell death studies and
      bromodeoxyuridine immunohistochemistry indicated that the aforementioned
      differences in generation of DA neurons are not due to changes in survival or
      proliferation of DA cells, but rather to increased or decreased differentiation
      of mesencephalic precursors towards the DA phenotype. The results suggest that
      these effects are exerted via GABA receptors located on DA precursors, and are
      not an indirect consequence of effects on the serotonergic or glial cell
      population. Administration of GABA(A) receptor antagonists in the differentiation
      medium may help to obtain higher rates of DA neurons for potential use in cell
      therapy for Parkinson's disease.

PMID- 17525991
TI  - Effects of a mutation in the Drosophila porin gene encoding mitochondrial voltage
      dependent anion channel protein on phototransduction.
AB  - Mitochondrial porins, also know as VDACs (voltage-dependent anion channels), play
      an important role in regulating energy metabolism, apoptosis, and the transport
      of metabolites across the mitochondrial outer membrane. So far three distinct
      isoforms of VDAC (VDAC1-3) have been reported in vertebrates, but their functions
      remain unknown. The annotation database of the Drosophila melanogaster genome
      sequence has identified four genes (porin, CG17137, CG17139, and CG17140)
      encoding different isoforms of VDACs. We identified post-translational
      modifications of PORIN that are specific to D. melanogaster eyes. We also
      identified the P-element insertion in the porin gene, porin(G2294), that is
      homozygous viable whereas all the porin mutants previously reported are
      homozygous lethal at the pupal stage. The mutant does not show any defects in fly
      morphology, survival, and photoreceptor structure. The mutant, however, produces
      <10% of the normal level of wild-type (WT) porin transcripts and 16.5% of WT
      level of the PORIN protein. The P-element insertion affects only the expression
      of Class I transcript but not Class II transcript of the porin gene. Unlike in
      WT, the mutant displays an ERG (electroretinogram) that is not maintained during
      a prolonged light stimulus. The revertant obtained from remobilization of the P
      element in the mutant produces the WT level of porin transcripts and PORIN
      protein, and shows a normal ERG response. Our data suggest that the PORIN protein
      is important in maintaining a photoreceptor response during prolonged
      stimulation.

PMID- 17525992
TI  - Deletion of the Bax gene disrupts sexual behavior and modestly impairs motor
      function in mice.
AB  - Cell death is a nearly ubiquitous feature of the developing nervous system, and
      differential death in males and females contributes to several well studied sex
      differences in neuron number. Nonetheless, the functional importance of neuronal
      cell death has been subjected to few direct tests. Bax, a pro-apoptotic protein,
      is required for cell death in many neural regions. Deletion of the Bax gene in
      mice increases neuron number in several areas and eliminates sex differences in
      cell number in the brain and spinal cord. Here, sexual and motor behaviors were
      examined in Bax-/- mice and their wild-type siblings to test the functional
      consequences of preventing Bax-dependent cell death. Animals were gonadectomized
      in adulthood and provided with ovarian hormones or with testosterone for tests of
      feminine and masculine sexual behaviors, respectively. Wild-type mice exhibited a
      sex difference in feminine sexual behavior, with high lordosis scores in females
      and low scores in males. This sex difference was eliminated by Bax deletion, with
      very low receptivity exhibited by both male and female Bax-/- mice. Masculine
      sexual behavior was not sexually dimorphic among wild-type mice, but mounts and
      pelvic thrusts were nearly eliminated in Bax-/- mice of both sexes. Motor
      strength and performance at low speeds on a RotaRod apparatus did not differ by
      sex or Bax gene status. However, Bax-/- animals exhibited impairments on the
      RotaRod at higher speeds. Thus, developmental cell death may be required for
      masculine and feminine sexual behaviors and the fine tuning of motor
      coordination.

PMID- 17525993
TI  - Song and brain development in canaries raised under different conditions of
      acoustic and social isolation over two years.
AB  - Early isolation experiments indicate that male songbirds learn their songs during
      an early sensitive period, although later work has shown that some open-ended
      learners modify songs in later years. Recent isolation experiments suggest that
      in some species song has a stronger genetic basis than previously thought. This
      study raised domestic canaries under different combinations of acoustic and
      social isolation and followed song development into the second year. Males raised
      alone in acoustic isolation developed songs with normal syllables, but larger
      repertoires and also produced syllables with lower repetition rates when compared
      to controls. The smallest repertoire occurred in males raised in a peer group.
      Isolate males had a smaller song control nucleus HVC than controls, but there was
      no effect on nucleus RA or on brain weight in general. In the second year, after
      introduction into a large normal colony, isolate and peer group males adjusted
      their syllable repertoire to normal size. In particular, the isolates reduced
      their repertoire even though the size of HVC showed a significant increase in
      volume. However, songs of isolate and peer group males still differ in repetition
      rate and number of single syllables in the common aviary. In contrast, control
      males showed low syllable turnover and no significant change in repertoire size.
      Nor did they show any significant change in the volumes of song control nuclei.
      It seems that complete isolation affects only some aspects of song and brain
      development, and later socialization corrects some but not all of these in the
      second year.

PMID- 17525994
TI  - Species differences in auditory processing dynamics in songbird auditory
      telencephalon.
AB  - The caudomedial nidopallium (NCM) of songbirds is a telencephalic area involved
      in the auditory processing and memorization of complex vocal communication
      signals. We used pure tone stimuli and multiunit electrophysiological recordings
      in awake birds to investigate whether the basic properties of song-responding
      circuits in NCM differ between canaries and zebra finches, two species whose
      songs are markedly different in their spectral and temporal organization. We
      found that the responses in zebra finch NCM are characterized by broad tuning and
      sustained responses that may facilitate the integration of zebra finch song
      syllables and call notes that are of long duration and have a broad harmonic
      structure. In contrast, we found that the responses in canary NCM show narrower
      tuning and less sustained responses over the time periods analyzed. These
      characteristics may contribute to enhanced processing of the narrow-band
      whistles, rapid trills, and steep frequency modulations that are prominent
      features of canary song. These species differences are much less pronounced in
      field L2, the direct thalamorecipient region that represents a preceding station
      in the central avian auditory pathway. NCM responses did not differ across sexes
      of either species, but field L2 did show wider tuning in zebra finch females
      relative to males. In sum, species differences in the response properties of NCM
      likely reflect selectivity for the acoustic elements of each species' vocal
      repertoire.

PMID- 17525995
TI  - Renal artery stenosis: what we don't know won't hurt us. ...right?

PMID- 17525996
TI  - Increased Smad1 expression and transcriptional activity enhances trans
      differentiation of hepatic stellate cells.
AB  - Smad1 is a receptor-activated intracellular signaling protein, which mediates
      signal transduction of bone morphogenetic proteins. Current study investigated
      the expression and transcriptional activity of Smad1 during hepatic stellate cell
      (HSC) activation. Rat HSCs were isolated from rats at 1, 2, 3 and 4 days after
      gavaged with carbon tetrachloride (CCl(4)) or corn oil. RT-PCR, Western blot, gel
      shift assay and luciferase assay were employed to examine Smad1 expression and
      transcriptional activity, respectively. CCl(4)-cirrhotic liver fat-storing cells
      8B (CFSC-8B) cells were infected with recombinant adenoviruses of Smad1 and/or
      Smad1 shRNA. Both mRNA and protein levels of Smad1 were significantly increased
      at 48 h after gavage of CCl(4). Gel shift assays demonstrated a significant
      increase in nuclear Smad1 in day 9 HSCs. Transfection of HSCs with Smad1
      responsible luciferase indicated an increase in Smad1 transcriptional activity in
      day 6 HSCs (1.563 +/- 0.229 in day 6 versus 0.785 +/- 0.192 in day 3). When CFSC
      8B cells were infected with adenoviruses with Smad1 or Smad1 short hairpin RNA
      (shRNA), there was an increase or decrease in Smad1 mRNA and protein,
      respectively. Smooth muscle alpha-actin expression was increased or decreased
      according to induction or reduction of Smad1. In conclusion, there were
      significantly increases in Smad1 expression and transcriptional activity during
      in vivo activation of hepatic stellate cells.

PMID- 17525997
TI  - Stimulation by ghrelin of p42/p44 mitogen-activated protein kinase through the
      GHS-R1a receptor: role of G-proteins and beta-arrestins.
AB  - Results presented in this study indicate that in human embryonic kidney 293 cells
      (HEK 293), the ghrelin receptor growth hormone secretagogue receptor type 1a (GHS
      R1a) activates the extracellular signal-related kinases 1 and 2 (ERK 1/2) via
      three pathways. One pathway is mediated by the beta-arrestins 1 and 2, and
      requires entry of the receptor into a multiprotein complex with the beta
      arrestins, Src, Raf-1, and ERK 1/2. A second pathway is G(q/11)-dependent and
      involves a Ca(2+)-dependent PKC (PKCalpha/beta) and Src. A third pathway is G(i)
      dependent and involves phosphoinositide 3-kinase (PI3K), PKCepsilon, and Src. Our
      current study reveals that G(i/o)- and G(q/11)-proteins are crucially involved in
      the beta-arrestin-mediated ERK 1/2 activation. These results thus support the
      view that the beta-arrestins act as both scaffolding proteins and signal
      transducers in ERK 1/2 activation, as reported for other receptors. The different
      pathways of ERK 1/2 activation suggest that binding to GHS-R1a activates ERK 1/2
      pools at different locations within the cell, and thus probably with different
      physiological consequences.

PMID- 17525999
TI  - CT imaging of coronary stent patency.

PMID- 17526001
TI  - The DES debate: staying focused on our patients.

PMID- 17526000
TI  - Transplantation of Schwann cells and/or olfactory ensheathing glia into the
      contused spinal cord: Survival, migration, axon association, and functional
      recovery.
AB  - Schwann cells (SCs) and olfactory ensheathing glia (OEG) have shown promise for
      spinal cord injury repair. We sought their in vivo identification following
      transplantation into the contused adult rat spinal cord at 1 week post-injury by:
      (i) DNA in situ hybridization (ISH) with a Y-chromosome specific probe to
      identify male transplants in female rats and (ii) lentiviral vector-mediated
      expression of EGFP. Survival, migration, and axon-glia association were
      quantified from 3 days to 9 weeks post-transplantation. At 3 weeks after
      transplantation into the lesion, a 60-90% loss of grafted cells was observed. OEG
      only grafts survived very poorly within the lesion (<5%); injection outside the
      lesion led to a 60% survival rate, implying that the injury milieu was hostile to
      transplanted cells and or prevented their proliferation. At later times post
      grafting, p75(+)/EGFP(-) cells in the lesion outnumbered EGFP(+) cells in all
      paradigms, evidence of significant host SC infiltration. SCs and OEG injected
      into the injury failed to migrate from the lesion. Injection of OEG outside of
      the injury resulted in their migration into the SC-injected injury site, not via
      normal-appearing host tissue but along the pia or via the central canal. In all
      paradigms, host axons were seen in association with or ensheathed by transplanted
      glia. Numerous myelinated axons were found within regions of grafted SCs but not
      OEG. The current study details the temporal survival, migration, axon association
      of SCs and OEG, and functional recovery after grafting into the contused spinal
      cord, research previously complicated due to a lack of quality, long-term markers
      for cell tracking in vivo.

PMID- 17526003
TI  - Transcriptome changes associated with instructed learning in the barn owl
      auditory localization pathway.
AB  - Owls reared wearing prismatic spectacles learn to make adaptive orienting
      movements. This instructed learning depends on re-calibration of the midbrain
      auditory space map, which in turn involves the formation of new synapses. Here we
      investigated whether these processes are associated with differential gene
      expression, using longSAGE. Newly fledged owls were reared for 8-36 days with
      prism or control lenses at which time the extent of learning was quantified by
      electrophysiological mapping. Transciptome profiles were obtained from the
      inferior colliculus (IC), the major site of synaptic plasticity, and the optic
      tectum (OT), which provides an instructive signal that controls the direction and
      extent of plasticity. Twenty-two differentially expressed sequence tags were
      identified in IC and 36 in OT, out of more than 35,000 unique tags. Of these,
      only four were regulated in both structures. These results indicate that
      regulation of two largely independent gene clusters is associated with synaptic
      remodeling (in IC) and generation of the instructive signal (in OT). Real-time
      PCR data confirmed the changes for two transcripts, ubiquitin/polyubiquitin and
      tyrosine 3-monooxgenase/tryotophan 5-monooxygenase activation protein, theta
      subunit (YWHAQ; also referred to as 14-3-3 protein). Ubiquitin was downregulated
      in IC, consistent with a model in which protein degradation pathways act as an
      inhibitory constraint on synaptogenesis. YWHAQ was up-regulated in OT, indicating
      a role in the synthesis or delivery of instructive information. In total, our
      results provide a path towards unraveling molecular cascades that link
      naturalistic experience with synaptic remodeling and, ultimately, with the
      expression of learned behavior.

PMID- 17526004
TI  - Inflammometry and asthma: onto the next level.

PMID- 17526005
TI  - Exhaled nitric oxide after a single dose of intramuscular triamcinolone in
      children with difficult to control asthma.
AB  - In a previous study, we reported that intramuscular (IM) triamcinolone improves
      symptoms in children with difficult asthma. In 2005, we revised our difficult
      asthma protocol to include assessment of airway inflammation, both directly using
      sputum induction and indirectly by measurement of exhaled nitric oxide (eNO). In
      this retrospective review, we aimed to describe (i) the changes in eNO and
      symptoms after a single 60 mg dose of IM triamcinolone and (ii) the changes in
      inflammatory markers in the subgroup with non-eosinophilic asthma (i.e., an
      induced sputum eosinophil differential count <2.0%). Seven children received IM
      triamcinolone during the study period. In all children, symptom scores fell in
      the week following the IM injection (P < 0.01 vs. the pre-treatment week), and
      remained reduced for up to 6 weeks. eNO also fell within a week after IM therapy
      (P < 0.01), and remained reduced for up to 4 weeks. Non-eosinophilic asthma was
      definitively identified in three children, and in this group, eNO and symptoms
      fell after the IM injection. We conclude that IM triamcinolone therapy reduces
      both eNO and symptoms for up to 4 weeks in children with difficult asthma. Our
      data provide preliminary evidence that IM triamcinolone is an effective anti
      inflammatory therapy in children with induced sputum non-eosinophilic asthma.

PMID- 17526006
TI  - Is wheezing associated with decreased sleep quality in Sri Lankan children? A
      questionnaire study.
AB  - AIM: To investigate the association between wheezing and impaired sleep in Sri
      Lankan children, aged 6-12 years; and, to report the prevalence of asthma-related
      symptoms in these subjects. METHODS: The International Study of Asthma and
      Allergies in Childhood questionnaire and a separate sleep questionnaire were
      completed. RESULTS: Of 800 originally distributed questionnaires, 652 were
      analyzed. Wheezing was present in 89 children (14%). Within this group, 66%
      reported wheezing in the last 12 months. Wheezing children had a significantly
      higher presence of snoring, restless sleep, nocturnal awakenings and daytime
      tiredness. Wheezing was found to be independently associated with restless sleep
      (odds ratio (OR) = 2.4). There was no association between wheezing and
      difficulties falling asleep, nocturnal awakenings, apneas, and daytime sleepiness
      and tiredness. After adjusting for possible confounders, the following
      significant associations were present: snoring and apneas (OR = 1.6), chronic
      rhinitis and apneas (OR = 1.6), snoring and restless sleep (OR = 3.2), chronic
      rhinitis and restless sleep (OR = 2.1), and hayfever and daytime tiredness (OR =
      4.3). Wheezing was related to an increased risk of snoring (OR = 2.8) and
      subjects with chronic rhinitis had also an increased risk of snoring (OR = 1.7),
      adjusting for possible confounders. CONCLUSION: The sleep of wheezing children
      was impaired compared with their non-wheezing peers, resulting in an increased
      prevalence of daytime tiredness. Upper airway symptoms, such as chronic rhinitis
      or hayfever, should be carefully considered in these children, as they might be
      responsible for these sleep problems.

PMID- 17526007
TI  - Lung volumes and distribution of ventilation in survivors to congenital
      diaphragmatic hernia (CDH) during infancy.
AB  - The assessment of lung volumes, particularly functional residual capacity (FRC),
      is crucial for understanding lung development during infancy in CDH patients.
      AIM: To evaluate changes in lung function during infancy in subjects with CDH
      treated with a "gentle ventilation" technique and delayed surgery strategy in the
      neonatal period. METHODS: 13 CDH infants were studied twice and compared with a
      population of 28 healthy infants (HI). Tidal-Volume (Vt), respiratory rate (RR)
      and time to peak expiratory flow/expiratory time ratio (tPTEF/Te) were measured
      with an ultrasonic flow meter; Compliance (Crs) and Resistance (Rrs) of the
      respiratory system were studied with the single occlusion technique; FRC and Lung
      Clearance Index (LCI), were assessed with the sulfur hexafluoride (SF6) wash
      in/wash-out technique. The differences between the first (T1) and second (T2)
      measurement in the CDH group were assessed by the Student's t-test for paired
      values. For each set of measurement (T1 and T2) the values were compared with HI
      by Student's t-test. RESULTS: Mean age at test was 7.5 +/- 5.2 months for HI, 4.5
      +/- 2.5 at T1 and 11.9 +/- 4.5 months at T2 for CDH infants. At T1 there were no
      significant differences between CDH infants and HI in Vt, Crs, and FRC, while
      tPTEF/te ratio was lower and RR, Rrs, and LCI were higher in CDH patients than in
      HI. At T2 Vt, Crs, and FRC remained normal in CDH patients as well as RR that, at
      this time was not different between CDH and healthy infants; tPTEF/te remained
      below and Rrs and LCI remained above normal ranges, indicating a persistent
      impairment in lower airways patency. CONCLUSIONS: Lung function in infants with
      severe CDH is characterized by a persistent impairment in airways patency and
      significant inhomogeneity of ventilation, suggesting a peripheral bronchial
      obstruction even if the other lung function tests are within normal ranges.

PMID- 17526008
TI  - Polytetrafluoroethylene-covered stent deployment in the setting of Kawasaki
      disease.

PMID- 17526010
TI  - Resection alone in 58 children with limited stage, lymphocyte-predominant Hodgkin
      lymphoma-experience from the European network group on pediatric Hodgkin
      lymphoma.
AB  - BACKGROUND: Lymphocyte-predominant Hodgkin lymphoma (LPHL) is a rare, CD20
      positive, good prognostic lymphoma in children. Patients with early-stage LPHL
      who underwent successful surgical lymph node resection alone have been reported.
      To clarify the optimum treatment strategy in children, European study groups were
      asked to report their experience of surgery alone used in the treatment of
      pediatric LPHL. METHODS: Data from 58 patients were collected by the French
      Society for Pediatric Cancers, the German-Austrian Pediatric Study Group/German
      Society of Pediatric Oncology and Hematology (Germany), and the Children's Cancer
      and Leukaemia Group (United Kingdom). In total, there were 50 boys and 8 girls,
      and the median age was 11 years (age range, 4-17 years). Fifty-four patients had
      stage IA disease, 2 patients had stage IIA disease, and 2 patients had stage IIIA
      disease. RESULTS: With a median follow-up of 43 months (range, 2-202 months), the
      overall survival rate was 100%, and the progression-free survival (PFS) rate was
      57%. Fifty-one of 58 patients achieved complete remission (CR) after surgery. In
      the CR group, the overall PFS rate was 67% (95% confidence interval, 51-82%). All
      seven patients who had residual disease after initial surgery developed
      recurrences (P = .003). Among 18 patients with stage IA LPHL who developed
      recurrent disease, 11 patients had local recurrences, and 7 patients recurred in
      stage IIA. One patient with stage IIIA disease presented with high-grade B-cell
      non-Hodgkin lymphoma at 10 years of follow-up. CONCLUSIONS: When complete
      resection was achieved, a substantial proportion of patients with surgically
      treated, early-stage LPHL experienced long-term remission and actually may have
      been cured.

PMID- 17526009
TI  - Myxovirus-1 and protein kinase haplotypes and fibrosis in chronic hepatitis C
      virus.
AB  - Candidate genes, including myxovirus resistance-1 (Mx1), protein kinase (PKR),
      transforming growth factor-beta1 (TGF-beta), interleukin-10 (IL-10), and
      interferon-gamma (IFN-gamma), were evaluated for associations with liver fibrosis
      in 374 treatment-naive patients with genotype-1 chronic HCV infection [194
      Caucasian Americans (CAs) and 180 African Americans (AAs)], using a genetic
      haplotype approach. Among the 18 haplotypes that occurred with a frequency >or=5%
      in the cohort overall, the Mx1-(-123C)-(+6886A)-(+19820G(379V))-(+38645T)
      (abbreviated Mx1-CAGT), and PKR-(+110T)-(+7949G)-(+13846A)-(+22937T)-(+40342T)
      (abbreviated PKR-TGATT) haplotypes were independently associated with less severe
      hepatic fibrosis (Ishak >or= 3 versus <3). These associations persisted after
      adjustment for potential confounders such as alcohol use, sex, age (which is
      strongly correlated with the estimated duration of HCV infection [Spearman's
      correlation coefficient (r(s)) = 0.6)], and race (for Mx1-CAGT: OR = 0.33; 95%
      CI: 0.16-0.68; P = 0.0027; and for PKR-TGATT: OR = 0.56; 95% CI: 0.32-0.98; P =
      0.0405). Population structure was evaluated using the structured association
      method using data from 161 ancestry-informative markers and did not affect our
      findings. We used an independent cohort of 34 AA and 160 CA in an attempt to
      validate our findings, although notable differences were found in the
      characteristics of the two patient groups. Although we observed a similar
      protective trend for the Mx1-CAGT haplotype in the validation set, the
      association was not statistically significant. CONCLUSION: In addition to other
      factors, polymorphisms in cytokine genes may play a role in the progression of
      HCV-related fibrosis; however, further studies are needed.

PMID- 17526011
TI  - Differentiation of oligodendrocytes in neurospheres derived from embryonic rat
      brain using growth and differentiation factors.
AB  - Studies on the isolation and propagation of multipotent neural precursors as
      neurospheres suggest their potential use in the reconstitution of neurons and
      oligodendrocytes in neurodegenerative diseases. To ensure that an adequate number
      of functionally relevant cells are present after transplantation, in vitro
      manipulation of cell fate before transplantation may be necessary to control the
      terminal phenotype of these cells. Using growth factors known to have a role in
      oligodendrocyte development such as sonic hedgehog, platelet-derived growth
      factor (PDGF), and basic fibroblast growth factor (FGF-2), we have tried to
      increase the number of oligodendroglia derived from E18 cortical neurospheres. We
      have shown that although all of the growth factor combinations induce the
      formation of oligodendroglia, they do so in varying proportions, with PDGF
      favouring the formation of oligodendrocyte progenitor cells and sonic hedgehog
      favouring the formation of mature oligodendrocytes. To further enhance the
      generation of oligodendroglia we exposed neurospheres to B104-cell conditioned
      medium (B104 CM). Long-term growth of the neurospheres in this B104 CM increased
      markedly the number of cells committed to the oligodendrocyte lineage,
      specifically oligodendrocyte progenitor cells. These were then referred to as
      oligospheres. Our results suggest that the oligosphere culture system may provide
      a valuable source of cells for the reconstitution of oligodendrocytes in
      neurologic disorders.

PMID- 17526012
TI  - Guanine derivatives modulate extracellular matrix proteins organization and
      improve neuron-astrocyte co-culture.
AB  - Guanine derivatives (GD) have been shown to exert relevant extracellular effects
      as intercellular messengers, neuromodulators in the central nervous system, and
      trophic effects on astrocytes and neurons. Astrocytes have been pointed out as
      the major source of trophic factors in the nervous system, however, several
      trophic effects of astrocytic-released soluble factors are mediated through
      modulation of extracellular matrix (ECM) proteins. In this study, we investigated
      the effects of guanosine-5'-monophosphate (GMP) and guanosine (GUO) on the
      expression and organization of ECM proteins in cerebellar astrocytes. Moreover,
      to evaluate the effects of astrocytes pre-treated with GMP or GUO on cerebellar
      neurons we used a neuron-astrocyte coculture model. GMP or GUO alters laminin and
      fibronectin organization from a punctate to a fibrillar pattern, however, the
      expression levels of the ECM proteins were not altered. Guanine derivatives
      induced alteration of ECM proteins organization is mediated by activation of
      mitogen activated protein kinases (MAPK), CA(2+)-calmodulin-dependent protein
      kinase II (CaMK-II), protein kinase C (PKC), and protein kinase A (PKA) pathways.
      Furthermore, astrocytes treated with GMP or GUO promoted an increased number of
      cerebellar neurons in coculture, without altering the neuritogenesis pattern. No
      proliferation of neurons or astrocytes was observed due to GMP or GUO treatment.
      Our results show that guanine derivatives promote a reorganization of the ECM
      proteins produced by astrocytes, which might be responsible for a better
      interaction with neurons in cocultures.

PMID- 17526013
TI  - Creatine treatment promotes differentiation of GABA-ergic neuronal precursors in
      cultured fetal rat spinal cord.
AB  - Creatine is a substrate of cytosolic and mitochondrial creatine kinases. Its
      supplementation augments cellular levels of creatine and phosphocreatine, the
      rate of ATP resynthesis, and improves the function of the creatine kinase energy
      shuttle. High cytoplasmatic total creatine levels have been reported to be
      neuroprotective by inhibiting apoptosis. In addition, creatine has direct
      antioxidant effects, which may be of importance in amyotrophic lateral sclerosis.
      In the present study, we investigated the effects of creatine [5 mM] on survival
      and differentiation of cultured GABA-immunoreactive (-ir) and choline
      acetyltransferase (ChAT)-ir rat spinal cord neurons. Furthermore, we addressed
      the neuroprotective potential of creatine supplementation against 3
      nitropropionic acid (3-NP) induced toxicity. General cell survival and total
      neuronal cell density were not altered by chronic creatine treatment. We found,
      however, after chronic creatine and short-term creatine exposure a significantly
      higher density of GABA-ir neurons hinting to a differentiation-inducing mechanism
      of creatine. This notion is further supported by a significant higher content of
      GAD after creatine exposure. Creatine supplementation also exerted a partial, but
      significant neuroprotection for GABA-ir neurons against 3-NP induced toxicity.
      Interestingly, chronic creatine treatment did not alter cell density of ChAT-ir
      neurons but promoted their morphologic differentiation. Cell soma size and number
      of primary neurites per neuron were increased significantly after creatine
      supplementation. Taken together, creatine supplementation promoted the
      differentiation or the survival of GABAergic neurons and resulted in partial
      neuroprotection against 3-NP induced toxicity. The data suggest that creatine may
      play a critical role during development of spinal cord neurons.

PMID- 17526014
TI  - Instructive cross-talk between neural progenitor cells and gliomas.
AB  - Gliomas are the most common primary brain tumors and offer a poor prognosis in
      patients because of their infiltrative and treatment-resistant nature. The median
      survival time after diagnosis is approximately 11-12 months. There is a strong
      need for novel treatment modalities in targeting gliomas, and recent advances use
      neural progenitor cells as delivery systems for different therapeutic strategies.
      In this study, we show that rat embryonic neural progenitor cell (NPC) lines,
      transplanted at a distant site from a 3-day-preestablished glioma in the
      striatum, were able to migrate toward and colocalize with tumor isles without
      general spread into the brain parenchyma. Upon encounter with tumor, neural
      progenitor cells changed phenotype and became vimentin positive. These results
      demonstrate that transplanted neural progenitor cells respond to queues from a
      tumor and home to and exert an antitumor effect on the preestablished glioma,
      significantly decreasing the tumor volume with approximately 67% compared with
      control tumors after 1-2 weeks. Moreover, these early effects could be translated
      into increased survival times of animals treated with neural progenitor cell
      grafts 3 days after intrastriatal tumor inoculation. In contrast, there was no
      activation or migration of endogenous subventricular zone (SVZ) neuroblasts in
      response to an intrastriatal syngeneic tumor. In conclusion, NPC possess the
      ability to influence tumor growth as well as respond to queues from the tumor or
      tumor microenvironment, demonstrating a cross-talk between the cells.

PMID- 17526015
TI  - Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic
      syndrome in obese Zucker fa/fa rats.
AB  - This study investigated the effects of rimonabant (SR141716), an antagonist of
      the cannabinoid receptor type 1 (CB1), on obesity-associated hepatic steatosis
      and related features of metabolic syndrome: inflammation (elevated plasma levels
      of tumor necrosis factor alpha [TNFalpha]), dyslipidemia, and reduced plasma
      levels of adiponectin. We report that oral treatment of obese (fa/fa) rats with
      rimonabant (30 mg/kg) daily for 8 weeks abolished hepatic steatosis. This
      treatment reduced hepatomegaly, reduced elevation of plasma levels of enzyme
      markers of hepatic damage (alanine aminotransferase, gamma glutamyltransferase,
      and alkaline phosphatase) and decreased the high level of local hepatic TNFalpha
      currently associated with steatohepatitis. In parallel, treatment of obese
      (fa/fa) rats with rimonabant reduced the high plasma level of the proinflammatory
      cytokine TNFalpha and increased the reduced plasma level of the anti-inflammatory
      hormone adiponectin. Finally, rimonabant treatment also improved dyslipidemia by
      both decreasing plasma levels of triglycerides, free fatty acids, and total
      cholesterol and increasing the HDLc/LDLc ratio. All the effects of rimonabant
      found in this study were not or only slightly observed in pair-fed obese animals,
      highlighting the additional beneficial effects of treatment with rimonabant
      compared to diet. These results demonstrate that rimonabant plays a
      hepatoprotective role and suggest that this CB1 receptor antagonist potentially
      has clinical applications in the treatment of obesity-associated liver diseases
      and related features of metabolic syndrome.

PMID- 17526016
TI  - Enhanced accumulation of phosphorylated alpha-synuclein in double transgenic mice
      expressing mutant beta-amyloid precursor protein and presenilin-1.
AB  - A recent report showed that the accumulation of alpha-synuclein (alpha-syn) was
      detected in the brains of one-third of Alzheimer's disease and Down syndrome
      patients. However, the relationship between amyloid-beta protein (Abeta) and
      alpha-syn remains unclear. We analyzed the relation between the mutation of
      presenilin-1 (PS-1) and the pathological features of beta-amyloidosis and alpha
      synucleinopathy. We generated doubly transgenic mice overexpressing mutant beta
      amyloid precursor protein (betaAPP; Tg2576) and mutant PS-1 (PS1L286Vtg; line
      198) and analyzed 19 double Tg betaAPP(+)/PS(+) mice at 5-23 months (young to
      old), 23 age-matched single Tg betaAPP(+)/PS(-) mice, and 11 non-Tg littermates.
      Immunohistochemical comparison was performed in these three groups by counting
      the area and the number of alpha-syn- or phosphorylated alpha-syn (palpha-syn)
      positive dystrophic neurites per plaque (ASPDN, pASPDN). The acceleration of
      Abeta pathology was found with earlier onset and exaggerated numbers in double Tg
      betaAPP(+)/PS(+) compared with single Tg betaAPP(+)/PS(-) mouse brains. The
      accumulation of ASPDN and pASPDN was also accelerated in double Tg
      betaAPP(+)/PS(+) compared with single Tg betaAPP(+)/PS(-) mouse brains,
      especially in pASPDN. The number and area of alpha-syn and palpha-syn, and the
      ratio of palpha-syn positive neurites were significantly higher in double Tg
      betaAPP(+)/PS(+) than in single Tg betaAPP(+)/PS(-) mouse brains in middle-aged
      and old groups. Additional overexpression of mutant PS-1 accelerated Abeta
      induced alpha-synucleinopathy and further facilitated the phosphorylation of
      alpha-syn, suggesting a direct association between mutant PS-1 and
      phosphorylation of alpha-syn.

PMID- 17526017
TI  - Functional ryanodine receptors are expressed by human microglia and THP-1 cells:
      Their possible involvement in modulation of neurotoxicity.
AB  - Ryanodine receptors (RyRs) are intracellular Ca(2+) channels that mediate the
      release of calcium from internal stores and therefore play an important role in
      Ca(2+) signaling and homeostasis. Three RyR isoforms have been described thus
      far, and various areas of brain are known to express each of them. It is well
      established that neurons can express different RyR isoforms, but it is not known
      whether microglial cells do so. In the present study we showed that cultured
      human microglia from both fetal and adult brain specimens express mRNA for RyR1
      and RyR2, whereas RyR3 mRNA can be detected only in fetal microglial cells.
      Calcium spectrofluorometry showed that high levels of the RyR agonist 4-chloro-m
      cresol (4-CmC, 1-5 mM) induced elevation of intracellular Ca(2+) concentration
      ([Ca(2+)](i)) in both types of cultured human microglial cells. This effect was
      attenuated by the RyR antagonist 1,1'-diheptyl-4,4'-bipyridinium dibromide (DHBP,
      10 microM). Neurotoxicity of conditioned medium from human microglia and THP-1
      monocytic cells stimulated with a combination of interferon-gamma (IFN-gamma)
      with either lipopolysaccharide (LPS) or alpha-synuclein was diminished by DHBP.
      It was also diminished by 4-CmC at concentrations approximately 100-fold lower
      than those used to stimulate intracellular Ca(2+) release. These data indicate
      that human microglial cells express functional RyRs and that selective RyR
      ligands exert antineurotoxic action on this cell type. Therefore, RyR ligands may
      represent a novel class of compounds that have utility in reducing microglial
      mediated inflammation, which is believed to contribute to the pathogenesis of a
      number of neurodegenerative disorders including Alzheimer's disease and
      Parkinson's disease.

PMID- 17526018
TI  - Activation of epidermal growth factor receptors in astrocytes: from development
      to neural injury.
AB  - The epidermal growth factor receptor (EGFR) pathway controls the phenotypic
      characteristics of astrocytes. In the developing central nervous system (CNS),
      activation of the EGFR pathway induces astrocyte differentiation, forming the
      cribriform structure that surrounds axons and providing a supportive environment
      for neurons. In the adult CNS, the EGFR pathway is absent from astrocytes but is
      highly up-regulated and activated following neuronal injury. Activation of the
      EGFR pathway triggers quiescent astrocytes to become reactive astrocytes.
      Although astrocytes regulated by the EGFR pathway play constructive roles in the
      developing CNS, astrocytes that become reactive in response to activation of the
      EGFR pathway appear to be destructive to neurons in the adult CNS. The
      reappearance and activation of EGFRs in astrocytes under pathological conditions
      may activate a developmental process in an adult tissue. Regulation of EGFR
      function in astrocytes may be a new therapeutic strategy for the treatment of
      neural disorders.

PMID- 17526019
TI  - Astroglia overexpressing heme oxygenase-1 predispose co-cultured PC12 cells to
      oxidative injury.
AB  - The mechanisms responsible for the progressive degeneration of dopaminergic
      neurons and pathologic iron deposition in the substantia nigra pars compacta of
      patients with Parkinson's disease (PD) remain unclear. Heme oxygenase-1 (HO-1),
      the rate-limiting enzyme in the oxidative degradation of heme to ferrous iron,
      carbon monoxide, and biliverdin, is upregulated in affected PD astroglia and may
      contribute to abnormal mitochondrial iron sequestration in these cells. To
      determine whether glial HO-1 hyper-expression is toxic to neuronal compartments,
      we co-cultured dopaminergic PC12 cells atop monolayers of human (h) HO-1
      transfected, sham-transfected, or non-transfected primary rat astroglia. We
      observed that PC12 cells grown atop hHO-1 transfected astrocytes, but not the
      astroglia themselves, were significantly more susceptible to dopamine (1 microM)
      + H(2)O(2) (1 microM)-induced death (assessed by nuclear ethidium monoazide
      bromide staining and anti-tyrosine hydroxylase immunofluorescence microscopy)
      relative to control preparations. In the experimental group, PC12 cell death was
      attenuated significantly by the administration of the HO inhibitor, SnMP (1.5
      microM), the antioxidant, ascorbate (200 microM), or the iron chelators,
      deferoxamine (400 microM), and phenanthroline (100 microM). Exposure to
      conditioned media derived from HO-1 transfected astrocytes also augmented PC12
      cell killing in response to dopamine (1 microM) + H(2)O(2) (1 microM) relative to
      control media. In PD brain, overexpression of HO-1 in nigral astroglia and
      accompanying iron liberation may facilitate the bioactivation of dopamine to
      neurotoxic free radical intermediates and predispose nearby neuronal constituents
      to oxidative damage.

PMID- 17526020
TI  - Differential effects of polyglutamine proteins on nuclear organization and
      artificial reporter splicing.
AB  - Nuclear inclusions formed by proteins with expanded polyglutamine tracts are
      found in several neurodegenerative diseases. The effect of nuclear inclusions
      formed by these disease proteins on the functional organization of the nucleus is
      only partially understood. In particular, it is not known whether polyglutamine
      disease proteins disrupt the function of Cajal bodies, which are subnuclear
      domains that play a role in the biogenesis of small nuclear ribonucleoproteins
      (snRNPs). snRNPs are an integral part of the pre-mRNA splicing machinery, so it
      is possible that mutant proteins that alter Cajal body activity indirectly affect
      pre-mRNA splicing. Here, we evaluate three different polyglutamine disease
      proteins--ataxin-1, ataxin-3, and huntingtin--for their ability to disrupt Cajal
      body localization and reduce the splicing of an artificial reporter in HeLa
      cells. Consistent with previous observations, ataxin-1 inclusions do not
      drastically alter the localization of Cajal bodies. In contrast, ataxin-3
      inclusions associate with this structure. Inclusions formed by a fragment of the
      huntingtin protein do not associate with Cajal bodies or PML bodies, another
      subnuclear domain. Among the three disease proteins, only ataxin-3 significantly
      decreases the splicing of an artificial reporter. These results support the
      hypothesis that different mutant proteins vary in their ability to disrupt
      nuclear organization and function.

PMID- 17526021
TI  - Incidence of non-Hodgkin's lymphoma among individuals with chronic hepatitis B
      virus infection.
AB  - Although hepatitis C virus (HCV) infection has been shown to be associated with
      development of non-Hodgkin's lymphoma (NHL), few studies have investigated the
      association between chronic HBV infection and NHL. The purpose of this study was
      to compare the incidence of NHL between patients with and without chronic
      hepatitis B virus (HBV) infection. Using automated laboratory result and clinical
      data from two United States health systems, we identified individuals with
      chronic HBV infection from January 1, 1995 through December 31, 2001. Using each
      health system's population-based tumor registry, we identified all cases of NHL
      diagnosed through December 31, 2002. We excluded any individual with a history of
      NHL or human immunodeficiency virus (HIV). We fit Cox proportional hazards models
      to calculate hazard ratios comparing the incidence of NHL between chronic HBV
      infected patients (N = 3,888) and patients without HBV (N = 205,203) drawn from
      the source populations. We identified 8 NHL cases in the chronic HBV infection
      cohort and 111 cases in the comparison cohort. Patients with chronic HBV
      infection were 2.8 times more likely to develop NHL than matched comparison
      patients (adjusted hazard ratio = 2.80, 95% confidence interval = 1.16-6.75),
      after controlling for age, race, sex, income, Charlson comorbidity index, study
      site, and HCV infection. CONCLUSION: chronic HBV-infected patients were nearly 3
      times more likely to develop NHL than comparison patients.

PMID- 17526022
TI  - Dynamics of lactate concentration and blood oxygen level-dependent effect in the
      human visual cortex during repeated identical stimuli.
AB  - In vivo (1)H NMR spectroscopy at 7 T was utilized to measure the changes in
      lactate concentration upon repeated identical visual stimuli, each lasting for 2
      min. The average amplitude of these increases was found to be reduced over time
      (P < 0.01), from 0.13 +/- 0.02 micromol/g during the first half of the
      stimulation paradigm, to 0.06 +/- 0.02 micromol/g during the second half of the
      stimulation paradigm. In contrast, the blood oxygen level-dependent (BOLD) effect
      on the fMRI water signal and on the height of the total creatine signal at 3.03
      ppm was persistent during the whole observation period. This finding may suggest
      a differential adaptation of cortical output that is not reflected at the level
      of the global excitation-inhibition activity of the cortical canonical circuits.
      Alternative possibilities that could account for an adaptation of [Lac] changes
      are also discussed.

PMID- 17526023
TI  - Rho-kinase activation in endothelial cells contributes to expansion of infarction
      after focal cerebral ischemia.
AB  - Microcirculatory disturbances contribute to the expansion of infarct lesions
      after focal cerebral ischemia. Recently, it was shown that Rho-kinase involves in
      endothelial dysfunction via down-regulation of endothelial nitric oxide synthase
      function in a rodent stroke model. However, it is not clear whether endothelial
      Rho-kinase is activated in vivo or Rho-kinase activation contributes to
      microcirculatory disturbances after cerebral ischemia. In this study, we assessed
      the temporal and spatial profiles of Rho-kianse activity and the effect of the
      Rho-kinase inhibitor fasudil on microcirculatory disturbances in the focal brain
      ischemia. Rho-kinase activation was evaluated by analyzing the phosphorylation of
      adducin, a substrate of Rho-kinase, by immunohistochemistry. Staining for p
      adducin was found in endothelia in the ischemic area 6 hr after induction of
      ischemia. Microcirculatory disturbances and increased endothelial cell staining
      for von Willebrand factor (vWF) were observed in the same area. Postischemic
      treatment with fasudil suppressed endothelial Rho-kinase activation, preserved
      microcirculation, and inhibited endothelial cell vWF staining. These effects
      resulted in inhibition of infarct expansion and improvement of neurologic
      deficits. These findings indicate that Rho-kinase is activated in the endothelial
      cells and contributes to microcirculatory disturbances in cerebral ischemia. The
      vascular protective effect of Rho-kinase inhibitors may be useful in the
      treatment of the acute phase of ischemic stroke.

PMID- 17526024
TI  - Aquaporin 9 changes in pyramidal cells before and is expressed in astrocytes
      after delayed neuronal death in the ischemic hippocampal CA1 region of the
      gerbil.
AB  - In the present study, we observed changes of aquaporin 9 (AQP9) in the
      hippocampus induced by 5 min of ischemia in gerbils. In sham-operated animals,
      weak AQP9 immunoreactivity was detected in the stratum pyramidale of the
      hippocampus. AQP9 immunoreactivity, and its protein level in the CA1 region began
      to increase significantly at 6 hr and peaked 24 hr after ischemia. In the CA2/3
      region, AQP9 immunoreactivity significantly increased at 12 hr after ischemia.
      Thereafter, AQP9 immunoreactivity in the hippocampus decreased continuously with
      time. From 4 days after ischemia, AQP9 immunoreactivity in the CA1 region was
      expressed and increased in glial components in the strata oriens and radiatum.
      Based on double-immunofluorescence staining, many AQP9-immunoreactive glial cells
      in the CA1 region were identified as astrocytes. In a reverse transcription
      polymerase chain reaction study, AQP9 mRNA levels significantly increased in the
      CA1 region at 6 hr after ischemia, and thereafter AQP9 mRNA levels decreased with
      time after ischemia. In addition, the water content in the gerbil hippocampus was
      highest 3 hr after ischemia/reperfusion; thereafter, water content in the
      ischemic hippocampus was higher than that in the sham-operated group. This result
      shows how AQP9 in the gerbil hippocampus changes in neurons and is expressed in
      astrocytes before and after delayed neuronal death, respectively, after ischemia.
      These results indicate that changes in AQP9 in ischemic CA1 pyramidal cells may
      be related to delayed neuronal death and that the expression of AQP9 in
      astrocytes is related to gliosis in the CA1 region after transient forebrain
      ischemia.

PMID- 17526025
TI  - Redox-dependent and ligand-independent trans-activation of insulin receptor by
      globular adiponectin.
AB  - Adiponectin/ACRP30 is an adipose tissue-derived hormone with antiatherogenic,
      antidiabetic, and insulin-sensitizing properties. Although the metabolic effects
      of adiponectin on glucose and lipid metabolism are well known, the signaling
      pathways triggered by adiponectin receptors remain to be elucidated. We report
      evidence that in hepatic cells, adiponectin stimulation produces a transient
      burst of reactive oxygen species (ROS) through activation of the small GTPase
      Rac1 and 5-lypoxigenase. Furthermore, adiponectin-induced oxidants cause the
      oxidation/inhibition of protein-tyrosine phosphatase (PTP) 1B, one of the major
      phosphotyrosine phosphatases involved in the control of insulin receptor
      phosphorylation. Adiponectin causes increased association of PTP1B to insulin
      receptor and the oxidation/inhibition of the phosphatase, ultimately provoking
      the ligand-independent trans-phosphorylation of insulin receptor. We also report
      evidence that redox signaling plays a key role in both mitogen-activated protein
      kinase activation and hepatic glucose consumption induced by adiponectin.
      CONCLUSION: These results point to ROS as critical regulators of the cross-talk
      between adiponectin and insulin pathways and provide a redox-based molecular
      mechanism for the insulin-sensitizing function of adiponectin.

PMID- 17526026
TI  - Molecular characterization of the role of orphan receptor small heterodimer
      partner in development of fatty liver.
AB  - The orphan receptor Small Heterodimer Partner (SHP, NROB2) regulates metabolic
      pathways, including hepatic bile acid, lipid, and glucose homeostasis. We
      reported that SHP-deletion in leptin-deficient OB(-/-) mice increases insulin
      sensitivity, and prevents the development of fatty liver. The prevention of
      steatosis in OB(-/-)/SHP(-/-) double mutants is not due to decreased body weight
      but is associated with increased hepatic very-low-density lipoprotein (VLDL)
      secretion and elevated microsomal triglyceride transfer protein (MTP) mRNA and
      protein levels. SHP represses the transactivation of the MTP promoter and the
      induction of MTP mRNA by LRH-1 in hepatocytes. Adenoviral overexpression of SHP
      inhibits MTP activity as well as VLDL-apoB protein secretion, and RNAi knockdown
      of SHP exhibits opposite effects. The expression of SHP in induced in fatty
      livers of OB(-/-) mice and other genetic or dietary models of steatosis, and
      acute overexpression of SHP by adenovirus, result in rapid accumulation of
      neutral lipids in hepatocytes. In addition, the pathways for hepatic lipid uptake
      and lipogenic program are also downregulated in OB(-/-)/SHP(-/-) mice, which may
      contribute to the decreased hepatic lipid content. CONCLUSION: These studies
      demonstrate that SHP regulates the development of fatty liver by modulating
      hepatic lipid export, uptake, and synthesis, and that the improved peripheral
      insulin sensitivity in OB(-/-)/SHP(-/-) mice is associated with decreased hepatic
      steatosis.

PMID- 17526027
TI  - Activation of endoplasmic reticulum stress response by hepatitis viruses up
      regulates protein phosphatase 2A.
AB  - The up-regulation of protein phosphatase 2 A (PP2A) is an important factor
      leading to an inhibition of IFNalpha signaling caused by viral protein
      expression. Here, we describe the molecular mechanism involved in PP2Ac up
      regulation by HCV and HBV. HCV and HBV protein expression in cells induces an ER
      stress response leading to calcium release from the ER. HCV protein expression
      induces CREB activation, probably through calcium/calmodulin-dependent protein
      kinase. CREB binds to a CRE element in the promoter of PP2Ac and induces its
      transcriptional up-regulation. Because PP2Ac is involved in many important
      cellular processes including cell-cycle regulation, apoptosis, cell morphology,
      development, signal transduction and translation, its up-regulation during ER
      stress has potentially important implications.

PMID- 17526032
TI  - A crystalline supramolecular switch: controlling the optical anisotropy through
      the collective dynamic motion of molecules.

PMID- 17526033
TI  - Metallodynamers: neutral dynamic metallosupramolecular polymers displaying
      transformation of mechanical and optical properties on constitutional exchange.

PMID- 17526034
TI  - A general approach to chemo- and regioselective cyclotrimerization reactions.

PMID- 17526035
TI  - Structural studies on a lithium organo-amidocuprate in the solid state and in
      solution.

PMID- 17526036
TI  - Parameterization of peptide 13C carbonyl chemical shielding anisotropy in
      molecular dynamics simulations.
AB  - NMR chemical shielding anisotropy (CSA) relaxation is an important tool in the
      study of dynamical processes in proteins and nucleic acids in solution. Herein,
      we investigate how dynamical variations in local geometry affect the chemical
      shielding anisotropy relaxation of the carbonyl carbon nucleus, using the
      following protocol: 1) Using density functional theory, the carbonyl (13)C' CSA
      is computed for 103 conformations of the model peptide group N-methylacetamide
      (NMA). 2) The variations in computed (13)C' CSA parameters are fitted against
      quadratic hypersurfaces containing cross terms between the variables. 3) The
      predictive quality of the CSA hypersurfaces is validated by comparing the
      predicted and de novo calculated (13)C' CSAs for 20 molecular dynamics snapshots.
      4) The CSA fluctuations and their autocorrelation and cross correlation functions
      due to bond-length and bond-angle distortions are predicted for a chemistry
      Harvard molecular mechanics (CHARMM) molecular dynamics trajectory of Ca(2+)
      saturated calmodulin and GB3 from the hypersurfaces, as well as for a molecular
      dynamics (MD) simulation of an NMA trimer using a quantum mechanically correct
      forcefield. We find that the fluctuations can be represented by a 0.93 scaling
      factor of the CSA tensor for both R(1) and R(2) relaxations for residues in
      helix, coil, and sheet alike. This result is important, as it establishes that
      (13)C' relaxation is a valid tool for measurement of interesting dynamical events
      in proteins.

PMID- 17526037
TI  - Structure and dynamics of a discotic liquid-crystalline charge-transfer complex.
AB  - The structure of the charge-transfer complex hexakis(n-hexyloxy)triphenylene
      2,4,7-trinitro-9-fluorenone (HAT6-TNF) has been characterized by neutron
      scattering, X-ray diffraction (XRD), optical microscopy, and dielectric
      relaxation spectroscopy (DRS). On the basis of these data and the 1:1
      stoichiometry, a consistent structure for the complex is proposed. This structure
      differs markedly from structures previously proposed for similar materials,
      because the TNF molecules are found to be situated between the discotic columns
      rather than sandwiched between the discotic molecules of a given column. The
      addition of TNF to HAT6 is found to stiffen the structure, and quasi-elastic
      neutron scattering shows that the local dynamics of the discotic molecules in
      HAT6-TNF is slowed by the presence of the TNF molecules. This scenario is
      consistent with the observation of two VFT-type (VFT=Vogel-Fulcher-Tamman)
      dielectric relaxation processes that relate to the columnar glass transition and
      a polyethylene-like hindered glass transition originating from the nano-phase
      separated fraction of the aliphatic tails.

PMID- 17526038
TI  - A chemical-responsive supramolecular hydrogel from modified cyclodextrins.

PMID- 17526039
TI  - Regio- and stereoselective synthesis of enamides and dienamides by ruthenium
      catalyzed co-oligomerization of N-vinylamides with alkenes or alkynes.

PMID- 17526040
TI  - Comparison of the photophysical parameters for three perylene bisimide
      derivatives by single-molecule spectroscopy.
AB  - Characterization of the photophysical parameters for three perylene bisimide
      derivatives is presented. We exploited time-resolved and steady-state
      spectroscopy on both ensembles and single molecules under ambient as well as
      cryogenic (1.4 K) conditions. The finding is that these chromophores show
      extraordinary high fluorescence-emission rates, low intersystem crossing yields
      to the triplet state, and relatively short triplet lifetimes.

PMID- 17526041
TI  - One template, multiple rings: controlled iterative addition of macrocycles onto a
      single binding site rotaxane thread.

PMID- 17526043
TI  - Reactivity of "frustrated Lewis pairs": three-component reactions of phosphines,
      a borane, and olefins.

PMID- 17526042
TI  - Metal-catalyzed [1,2]-alkyl shift in allenyl ketones: synthesis of
      multisubstituted furans.

PMID- 17526044
TI  - Targeted charge-reversal nanoparticles for nuclear drug delivery.

PMID- 17526045
TI  - Analysis of Ras-induced oncogenic transformation of NIH-3T3 cells using
      differential-display 2-DE proteomics.
AB  - Ras proteins control at least three crucial signalling networks responsible for
      several cellular processes including anchorage independence, survival, and
      proliferation. Point mutations in one of the three ras genes are frequent in
      human tumours. In these tumours, Ras oncoproteins contribute significantly to the
      malignant phenotype, including deregulation of tumour-cell growth, apoptosis and
      invasiveness, and the ability to induce angiogenesis. Although significant
      strides have been made in understanding Ras biology, the collaborative actions of
      Ras effectors are still poorly understood. Here, we describe a proteomics
      approach to study global changes in protein expression in Ras-transformed NIH3T3
      cells. We exploited 2-D difference gel electrophoresis (DIGE) for pre-separation
      fluorescent protein labelling with three separate dyes to reduce gel-to-gel
      variability, to increase sensitivity and dynamic range of protein detection, and
      to enhance quantification of dysregulated proteins. Proteins dysregulated (> 1.5
      fold) by oncogenic Ras transformation reported to be implicated in Ras-regulated
      pathways include S-methyl-5-thioadenosine phosphorylase, stress-induced
      phosphoprotein 1, galectin-1, annexin A7 (synexin), 60S acidic ribosomal protein
      P0, serine/threonine protein phosphatase type 1 (PP1alpha) and prohibitin.
      Significantly, we report for the first time the expression of the newly
      discovered cytokine IL-25 (or IL-17E) in mouse embryonic fibroblast cells and its
      down-regulation (2.1-fold) upon Ras-induced oncogenic transformation.

PMID- 17526049
TI  - Avenues into complex materials: cooperative projects of the natural, engineering,
      and biosciences.

PMID- 17526050
TI  - Scale-up of upstream and downstream operations for the production of glucosamine
      using microbial fermentation.
AB  - Glucosamine is used to treat osteoarthritis or as a nutritional supplement. The
      synthesis, isolation, and purification of glucosamine play a crucial role in its
      industrial application. This work presents the production of glucosamine from
      microbial fermentation, and discusses the production problems at both the
      upstream and downstream operations when the fermentation process is scaled up.
      The cost evaluation of process design was used to analyze the feasibility of
      using microbial fermentation for the production of glucosamine. The calculated
      result shows that the cost of the production of glucosamine should be designed to
      be approximately between US$200 and 300/kg for the project to be viable.

PMID- 17526051
TI  - Liquid-phase separation of reactive dye by wood-rotting fungus: a
      biotechnological approach.
AB  - The live and pretreated mycelial pellets/biomass of Trametes versicolor was used
      for the biosorption of a textile dye, reactive blue MR (RBMR) from aqueous
      solution. The parameters that affect the biosorption of RBMR, such as contact
      time, concentration of dye and pH, on the extent of RBMR adsorption were
      investigated. To develop an effective and accurate design model for removal of
      dye, adsorption kinetics and equilibrium data are essential basic requirements.
      Lagergren first-order, second-order and Bangham's model were used to fit the
      experimental data. Results of the kinetic studies showed that the second order
      kinetic model fitted well for the present experimental data. The Langmuir,
      Freundlich and Temkin adsorption models were used for the mathematical
      description of the biosorption equilibrium. The biosorption equilibrium data
      obeyed well for Langmuir isotherm and the maximum adsorption capacities were
      found to be 49.8, 51.6, 47.4 and 46.7 mg/g for live, autoclaved, acid- and alkali
      pretreated biomass. The dye uptake capacity order of the fungal biomass was found
      as autoclaved > live > acid-treated > alkali-pretreated. The Freundlich and
      Temkin models were also able to describe the biosorption equilibrium on RBMR on
      live and pretreated fungal biomass. Acidic pH was favorable for the adsorption of
      dye. Studies on pH effect and desorption show that chemisorption seems to play a
      major role in the adsorption process. On comparison with fixed bed adsorption,
      batch mode adsorption was more efficient in adsorption of RBMR.

PMID- 17526052
TI  - Atemonate and Imuteran: novel Russian monoclonal antibody-based therapeutic
      agents.
AB  - The N. Blokhin National Cancer Research Center is one of the few Russian
      scientific institutions in which hybridoma technology of monoclonal antibody
      (mAb) production has been successfully established. Using this technology,
      several dozens of mAbs to various antigens of human leukocytes have been
      elaborated. These mAbs are widely used for immune status evaluation and for
      differential diagnostics of leukemias. Two mAbs were used to develop therapeutic
      drugs. Imuteran is a pharmaceutical form of mAb ICO-25 against a mucin-like
      antigen of human milk fat globules and proposed for treatment of epithelial cell
      originating cancers (breast, intestinal, ovarian, lung cancer, etc.). ThePhase II
      clinical study of this agent is now nearly completed, and preliminary results
      suggest Imuteran to be a promising anticancer agent with tumor-stabilizing
      activity, but patients should be carefully monitored for signs of allergic
      reactions. mAb ICO-90 against the CD3 antigen of human T lymphocytes was used to
      develop the therapeutic agent Atemonate proposed for treatment of acute
      transplant rejection. At present, the Phase II clinical study of this agent is
      over, and the results confirm the drug safety and efficacy for this indication.
      The drug is being registered at the Ministry of Healthcare and Social
      Development, and transfer to serial production is expected shortly.

PMID- 17526053
TI  - Soil bacterium Pseudomonas sp.: destroyer of mustard gas hydrolysis products.
AB  - A bacterial culture capable of utilizing products of mustard gas hydrolysis as a
      source of carbon was isolated from soil. This culture was tolerant to
      organochlorine substances in the hydrolysate. The bacterium was identified as
      Pseudomonas sp. The bacterium utilizes the major product of mustard gas
      hydrolysis, thiodiglycol, through two pathways. One involves the oxidation of the
      primary alcoholic groups in thiodiglycol, yielding thiodiglycolic and
      thioglycolic acids. The cleavage of the C-S bonds in these acids gives rise to
      acetate, which is then used further in the cell metabolism. The other pathway
      involves the cleavage of the C-S bond in the thiodiglycol molecule, yielding beta
      mercaptoethanol, which is transformed by Pseudomonas sp. into thioglycolic acid.
      The results show the promise of this bacterium for the bioremediation of mustard
      gas-contaminated soils.

PMID- 17526054
TI  - Safety assessment of genetically modified organisms of plant origin in the
      Russian Federation.
AB  - The beginning of the 21st century is characterized by growing interest in the
      problems of biosafety, which are determined, on the one hand, by the wide use of
      novel biotechnologies and the necessity to develop the adequate precautionary
      measures, and, on the other hand, by the objective threat of bioterrorism.
      Therefore, improvement of the estimation system for genetically modified (GM)
      sources of food and strengthening the control of their circulation are the urgent
      problems of modern biology and medicine. Russia is one of the countries where the
      estimation system of food products obtained from the GM sources is rather
      efficient. The key features of this system are the complex toxicological and
      epidemiological examinations. One of the main parts of GM food safety assessment
      is based upon detection of their potentially toxic properties, which could
      provoke unintended effects of the genetic modification.

PMID- 17526055
TI  - Oligonucleotide probes containing polylysine residues for fabrication of DNA
      chips on various solid surfaces.
AB  - Various materials, such as glass, plastic, metals, etc., are utilized for
      preparing DNA chips. In each particular case special approaches are used for
      immobilization of different oligonucleotide derivatives on the solid supports. We
      describe a general technique for DNA chips preparation on various unmodified
      surfaces using one type of oligonucleotide derivative, polylysine-oligonucleotide
      conjugates (PL-oligo). A long polyamine spacer in the PL-oligo conjugates
      provides a durable irreversible non-covalent immobilization onto a variety of
      solid supports and enough distance between oligonucleotides and the surface. The
      resulting DNA chips were shown to be useful for the detection of PCR DNA
      fragments and to be sensitive to single nucleotide discrepancies. They represent
      a promising instrument for revealing genetic diseases, genotyping viruses and
      bacteria, and for displaying their drug-resistant strains.

PMID- 17526056
TI  - Current awareness in human psychopharmacology.

PMID- 17526057
TI  - The roles of cyclin-dependent kinase 5 in dendrite and synapse development.
AB  - Since the isolation of cyclin-dependent kinase 5 (Cdk5), this proline-directed
      serine/threonine kinase has been demonstrated as an important regulator of
      neuronal migration, neuronal survival and synaptic functions. Recently, a number
      of players implicated in dendrite and synapse development have been identified as
      Cdk5 substrates. Neurite extension, synapse and spine maturation are all
      modulated by a myriad of extracellular guidance cues or trophic factors. Cdk5 was
      recently demonstrated to regulate signaling downstream of some of these
      extracellular factors, in addition to modulating Rho GTPase activity, which
      regulates cytoskeletal dynamics. In this communication, we summarize our existing
      knowledge on the pathways and mechanisms through which Cdk5 affects dendrite,
      synapse and spine development.

PMID- 17526058
TI  - Peptides derived from Cdk5 activator p35, specifically inhibit deregulated
      activity of Cdk5.
AB  - Normal Cdk5 activity, conferred mainly by association with its primary activator
      p35, is critical for normal function of the cell and must be tightly regulated.
      During neurotoxicity, p35 is cleaved to form p25, which becomes a potent and
      mislocalized hyperactivator of Cdk5, resulting in a deregulation of Cdk5
      activity. p25 levels have been found to be elevated in Alzheimer's disease (AD)
      brain and overexpression of p25 in a transgenic mouse results in the formation of
      phosphorylated tau, neurofibrillary tangles and cognitive deficits that are
      pathological hallmarks of AD. p25/Cdk5 also hyperphosphorylates neurofilament
      proteins that constitute pathological hallmarks found in Parkinson's disease and
      amyotrophic lateral sclerosis. The selective targeting of p25/Cdk5 activity
      without affecting p35/Cdk5 activity has been unsuccessful. In this review we
      detail our recent studies of selective p25/Cdk5 inhibition without affecting
      p35/Cdk5 or mitotic Cdk activities. We found that a further truncation of p25 to
      yield a Cdk5 inhibitory peptide (CIP) can specifically inhibit p25/Cdk5 activity
      in transfected HEK cells and primary cortical neurons. CIP was able to reduce tau
      hyperphosphorylation and neuronal death induced caused by p25/Cdk5 and further
      studies with CIP may develop a specific Cdk5 inhibition strategy in the treatment
      of neurodegeneration.

PMID- 17526059
TI  - Catechol-O-methyltransferase val108/158met genotype and response to antipsychotic
      medication in schizophrenia.
AB  - Catechol-O-methyltransferase (COMT) gene has been investigated as a possible
      candidate gene in schizophrenia. The most studied polymorphism has been the
      functional val108/158met polymorphism of this COMT gene. There is also some
      evidence that this polymorphism could be related to drug response to
      antipsychotics in schizophrenia. COMT enzyme inactivates dopamine and
      noradrenaline. Based mainly on the original dopamine theory of schizophrenia, our
      primary hypothesis was that the maintenance dose of antipsychotics would be
      higher in patients with the low activity COMT genotype. In this study we
      evaluated the current daily dosage of antipsychotics in 180 patients with
      schizophrenia in connection with the COMT genotype. We could not demonstrate any
      clearly significant effect of this particular COMT genotype in relation to the
      daily maintenance dosages of antipsychotics in patients with schizophrenia.

PMID- 17526060
TI  - Methods for one-sided testing of the difference between proportions and sample
      size considerations related to non-inferiority clinical trials.
AB  - Assessment of non-inferiority is often performed using a one-sided statistical
      test through an analogous one-sided confidence limit. When the focus of attention
      is the difference in success rates between test and active control proportions,
      the lower confidence limit is computed, and many methods exist in the literature
      to address this objective. This paper considers methods which have been shown to
      be popular in the literature and have surfaced in this research as having good
      performance with respect to controlling type I error at the specified level.
      Performance of these methods is assessed with respect to power and type I error
      through simulations. Sample size considerations are also included to aid in the
      planning stages of non-inferiority trials focusing on the difference in
      proportions. Results suggest that the appropriate method to use depends on the
      sample size allocation of subjects in the test and active control groups.

PMID- 17526061
TI  - Chemical introduction of reactive thiols into a viral nanoscaffold: a method that
      avoids virus aggregation.
AB  - The use of viral nanoparticles (VNPs) as building blocks for material fabrication
      has received particular attention in recent years. In earlier studies we showed
      the applicability of native gel electrophoresis in an agarose matrix as a useful
      method for the characterization of chemically modified VNPs. Here, we extend
      these studies and analyze the observed band pattern of intact Cowpea mosaic virus
      (CPMV) VNPs in agarose gels and show the applicability of native agarose gels for
      monitoring interparticle linkage of thiol-containing CPMV mutant particles. In
      addition, we report a protocol that allows the introduction of acetate-protected
      thiols to CPMV by means of a chemical reaction (rather than genetic
      modification). The advantage of this approach is that, by incorporating protected
      thiol groups, the formation of disulfide bonds leading to interparticle linkage
      is prevented. The resulting thiol-modified CPMV-SH(n) particles are stable, and
      following deprotection, the introduced thiols are reactive and can be labeled
      with thiol-selective reagents. They therefore provide a useful additional
      building block in the CPMV toolbox.

PMID- 17526062
TI  - CYP3A4 activity in the presence of organic cosolvents, ionic liquids, or water
      immiscible organic solvents.
AB  - P450 enzymes have attracted the attention of chemists for decades because of
      their impressive ability to catalyze the hydroxylation of inactivated C--H bonds.
      However, their use for synthesis in aqueous systems is limited. We report here a
      survey of the activity of purified human CYP3A4 in the presence of organic
      solvents or ionic liquids. We show that CYP3A4 tolerates only small amounts (<15
      %) of water-miscible organic cosolvents or ionic liquids before its activity
      toward testosterone drops below detection. [BMIM][PF(6)] in a biphasic system was
      less detrimental to enzyme activity, with 20 % of the activity remaining in the
      presence of 15 % of this ionic liquid. CYP3A4 activity in the absence of buffer
      was only >or=10 % in solvents of the alkane series, with a minimum of 0.85 %
      water, and with the addition of sucrose and testosterone before enzyme
      lyophilization. Biphasic solvent systems were more promising, with approximately
      85 % of the activity retained.

PMID- 17526064
TI  - Direct analysis of isopropylthioxanthone (ITX) in milk by high-performance liquid
      chromatography/tandem mass spectrometry.
AB  - A fast screening method is presented for detecting isopropylthioxanthone (ITX)
      contamination in milk. The method is based on direct high-performance liquid
      chromatography/tandem mass spectrometry (HPLC/MS/MS) analysis of milk samples.
      Sample preparation is limited to the addition of a deuterated ITX solution in
      acetonitrile that serves both as internal standard and to precipitate proteins.
      The method is highly accurate and sensitive. Isomeric specific analyses of 2-ITX
      and 4-ITX are possible at 6 microg/L levels with about 5% precision and accuracy.
      This approach has been used to check contamination in samples like milk, soy
      milk, baby milk, in their packaging material. Out of 37 milk samples analyzed, 16
      were positive with concentrations ranging from 173-439 microg/L for 2-ITX and
      from <6 (lower than limit of quantification) to 25 microg/L for 4-ITX.

PMID- 17526063
TI  - Immobilized protease-assisted synthesis of engineered cysteine-knot
      microproteins.

PMID- 17526065
TI  - Analysis of organic acid markers relevant to inherited metabolic diseases by
      ultra-performance liquid chromatography/tandem mass spectrometry as benzofurazan
      derivatives.
AB  - We describe a new approach applicable to the determination of organic acids that
      serve as diagnostic markers for several inherited metabolic disorders. We
      utilized liquid chromatography/tandem mass spectrometry for analysis of organic
      acid derivatives of a recently described benzofurazan reagent. The derivatization
      step was necessary to obtain organic acid derivatives suitable for analysis by
      reversed-phase liquid chromatography with high ionization efficiency for mass
      spectrometry in the positive-ion mode. In this work, a group of related
      dicarboxylic acid markers containing five or six carbon atoms were analyzed and
      validation was performed for glutaric and 3-hydroxyglutaric acids, the specific
      markers for glutaric acidemia type 1. Derivatization was achieved by reacting
      untreated urine with the derivatization reagent under mild conditions. The
      reaction mixture was analyzed on a C18 ultra-performance liquid chromatography
      (UPLC) column (50x2.1 mm, 1.7 microm) and detected in the multiple reaction
      monitoring mode in 5 min. Calibration curves were linear up to at least 1000
      microM with detection limits for glutaric and 3-hydroxyglutaric acids of 0.025
      and 0.02 microM, respectively (signal-to-noise ratio of 3). Intra-day (n=11) and
      inter-day (n=6) coefficients of variation were better than 11.2%. The assay was
      successfully applied to control (n=134) and glutaric acidemia type 1 (n=55) urine
      samples.

PMID- 17526066
TI  - Reducing fragmentation observed in the matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometric analysis of
      triacylglycerols in vegetable oils.
AB  - Edible oils consist primarily of triacylglycerols (TAGs). Matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectra of the oils are
      typically dominated by sodium adducts of these TAGs but also show prominent
      fragment ions (that do not contain sodium), which can interfere with analytical
      measurements of other components in oils. The fragments seemingly correspond to
      the loss of a fatty acid moiety from the sodiated TAGs as a sodium salt: RCOONa.
      However, a previous study suggested that the fragments actually arise from nearly
      complete fragmentation of unseen protonated TAGs. These authors suggested that
      the fragmentation occurs so rapidly and completely that protonated TAGs are not
      normally observed in the spectra of these oils. In this paper, we present
      evidence to support their theory and also demonstrate an approach to eliminate
      these interfering ions from the MALDI-TOF mass spectra via addition of a base to
      the matrix/sample mixture. The added base does not impede formation of the
      sodiated TAGs, but does significantly reduce the amount of fragments observed. We
      propose that this occurs by depleting the H+ ions from the matrix, thus
      preventing the formation of significant numbers of protonated TAGs in the first
      place. For measurements by MALDI-TOF, the relative abundances of the fragment
      ions are related to the strength of the base, and can be almost completely
      eliminated. However, in longer time-scale experiments such as in post-source
      decay and Fourier transform mass spectrometry, sodiated and non-sodiated
      diacylglycerol (DAG)-like fragments are present in spectra, regardless of whether
      or not a base is added to the sample.

PMID- 17526067
TI  - Quantitative determination of the cytidine deaminase inhibitor tetrahydrouridine
      (THU) in mouse plasma by liquid chromatography/electrospray ionization tandem
      mass spectrometry.
AB  - A number of anticancer drugs are cytidine analogues that undergo metabolic
      deactivation catalyzed by cytidine deaminase (CD). 3,4,5,6-Tetrahydrouridine
      (THU) is a potent inhibitor of CD, by acting as a transition-state analogue of
      its natural substrate cytidine. However, to date its pharmacokinetic properties
      have not been fully characterized, which has impaired its optimal preclinical
      evaluation and clinical use. We report a liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) assay for the sensitive, accurate and precise
      quantitation of THU in mouse plasma. Validation was performed according to FDA
      guidelines. The assay employed deuterated THU as the internal standard and an
      acetonitrile protein precipitation step. Separation, based on hydrophilic
      interaction chromatography, was achieved with an amino column and an isocratic
      mobile phase of 0.1% formic acid in acetonitrile and water followed by a wash.
      Chromatographic separation was followed by positive-mode electrospray ionization
      MS/MS detection in the multiple reaction monitoring (MRM) mode. The assay was
      accurate (92.5-109.9%) and precise (2.1-9.0%) in the concentration range of 0.2
      50 microg/mL. Recovery from plasma was near-complete (92.9-119.3%) and ion
      suppression was negligible (-17.5 to -0.2%). Plasma freeze/thaw stability (93.1
      102.1%), stability for 3 months at -80 degrees C (99.5-110.9%), and stability for
      4 h at room temperature (92.1-102.4%) were all in order. This assay is currently
      being used to quantitate THU in ongoing pharmacokinetic studies. In addition, the
      assay is expected to be a useful tool in any future studies involving co
      administration of THU with cytidine analogues.

PMID- 17526068
TI  - Analysis of steroid estrogens in water using liquid chromatography/tandem mass
      spectrometry with chemical derivatizations.
AB  - Even in trace amounts, estrogens such as 17beta-estradiol (E2), estrone (E1),
      estriol (E3), and 17alpha-ethinyl estradiol (EE2) may have adverse effects on
      humans and the aquatic ecosystem. Therefore, it is essential to be able to
      measure trace amounts of steroid estrogens in water. To date, most instruments
      are not sensitive enough to detect these chemicals in small samples of water.
      Sensitivity, however, may be improved by using appropriate derivatization
      reagents to modify the structures of these estrogens so that their ionization
      efficiency is increased, making them more detectable by liquid
      chromatography/mass spectrometry (LC/MS). This study uses dansyl chloride, 2
      fluoro-1-methylpyridinium p-toluenesulfonate (FMPTS), and pentafluorobenzyl
      bromide (PFBBr) as derivatization reagents to react with the phenolic estrogens
      to make them more detectable in water. We also test how environmental matrices
      (wastewater effluent, river water, and drinking water) influence the
      detectability of these estrogens. Both qualitative and semi-quantitative
      comparisons of these derivatization methods were made. We found that dansyl
      chloride derivatives created signal intensities one or two orders of magnitude
      greater than those normally found in underivatized estrogen standards. The
      signals derived by FMPTS were analyte-dependent, and the products derived from
      E1, E2, and EE2 produced 2.19 to 12.1 times the signal intensity of underivatized
      E1, E2, and EE2. The product derived from E3 produced weaker signals than that
      produced by underivatized E3. The PFBBr derivatives produced signals that were as
      much as 5.8 times those found in the underivatized estrogens. When these
      derivatization methods were applied to river water, drinking water and effluents
      from a sewage treatment plant (STP), the different matrices were found to
      significantly suppress the signals if we used electrospray ionization, though
      this influence became less significant if we used atmospheric pressure chemical
      ionization. This study suggests that PFBBr derivatization can best be used for
      the detection of these estrogens in complex environmental matrices such as river
      water and STP effluents and that the dansyl chloride derivatization is best used
      for clean samples such as drinking water.

PMID- 17526069
TI  - Combined approach for high-throughput preparation and analysis of plasma samples
      from exposure studies.
AB  - In drug discovery today, drug exposure is determined in preclinical efficacy and
      safety studies and drug effects are related to measured concentrations rather
      than to the administered dose. This leads to a strong increase in the number of
      bioanalytical samples, demanding the development of higher throughput methods to
      cope with the increased workload. Here, a combined approach is described for the
      high-throughput preparation and liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) analysis of drug levels in plasma samples from the preclinical
      efficacy and safety studies, i.e. exposure studies. Appropriate pharmacokinetic
      (PK) compartmental models were fitted to data from PK screening studies in the
      rat, which were subsequently used to simulate the expected plasma concentrations
      of the respective exposure studies. Information on the estimated drug
      concentrations was used to dilute the samples to appropriate concentration
      levels. A Tecan Genesis RSP liquid handling system was utilized to perform
      automated plasma sample preparation including serial dilution of standard
      solutions, dilution of plasma samples, addition of internal standard solution and
      precipitation with acetonitrile. This robotic sample preparation process
      permitted two studies of 1-96 samples each to be run simultaneously. To ensure
      the performance of this method the accuracy and precision for diazepam were
      examined. Two novel drugs were used to illustrate the suggested approach. In
      conclusion, our method for sample preparation of exposure samples, based on the
      combined use of PK simulations, a liquid handling system and a fast LC/MS/MS
      method, increased the throughput more than three times and minimized the errors,
      while maintaining the required accuracy and precision.

PMID- 17526071
TI  - Nonviral gene delivery: thinking of silica.

PMID- 17526070
TI  - RNAi therapeutics: SNALPing siRNAs in vivo.

PMID- 17526072
TI  - Non-viral gene delivery: stretching is the point.

PMID- 17526073
TI  - States of the heart.

PMID- 17526074
TI  - Study suggests limiting use of aspirin plus warfarin.

PMID- 17526075
TI  - Ask the doctor. Is my breathlessness a heart or lung problem?

PMID- 17526076
TI  - Ask the doctor. Does a low ejection fraction doom me to inactivity?

PMID- 17526077
TI  - Is the Canadian health care system better for neurologic care?

PMID- 17526078
TI  - Sudden infant death, bed-sharing and dummies: authors' reply.

PMID- 17526079
TI  - Bibliography. Current world literature. Cardiac failure.

PMID- 17526080
TI  - Meeting the needs of different research communities. PLoS launches three new
      community journals in 2005.

PMID- 17526081
TI  - Access for contributors: PLoS expands options for publication of research and
      comment.

PMID- 17526083
TI  - Bibliography. Current world literature. Pharmaceutical aspects, devices and
      techniques.

PMID- 17526082
TI  - Drug development papers in PLoS Medicine: how we try to spot a winner.

PMID- 17526084
TI  - Bibliography. Current world literature. Paediatrics.

PMID- 17526085
TI  - Prevention of death in COPD.

PMID- 17526086
TI  - Prevention of death in COPD.

PMID- 17526087
TI  - Prevention of death in COPD.

PMID- 17526088
TI  - Prevention of death in COPD.

PMID- 17526089
TI  - Posaconazole prophylaxis in hematologic cancer.

PMID- 17526090
TI  - Posaconazole prophylaxis in hematologic cancer.

PMID- 17526091
TI  - Posaconazole prophylaxis in hematologic cancer.

PMID- 17526092
TI  - Re: Atrioventricular junctional tachycardia with rate (acceleration)-dependent
      aberrancy.

PMID- 17526093
TI  - Treatment of symptomatic uterine fibroids.

PMID- 17526094
TI  - New treatments for diabetes.

PMID- 17526095
TI  - New treatments for diabetes.

PMID- 17526096
TI  - New treatments for diabetes.

PMID- 17526097
TI  - Rolling back the clock? MemoProve, a dietary supplement.

PMID- 17526098
TI  - Re: Why family medicine benefits from more women doctors.

PMID- 17526100
TI  - Occam's razor.

PMID- 17526099
TI  - Re: Moving on from Balint: embracing clinical supervision.

PMID- 17526101
TI  - Saving generalist medicine.

PMID- 17526102
TI  - Saving generalist medicine.

PMID- 17526103
TI  - Saving generalist medicine.

PMID- 17526104
TI  - Another EHR myth.

PMID- 17526105
TI  - The state of the science of HIV treatment approaches.

PMID- 17526106
TI  - The promise of ADAP.

PMID- 17526108
TI  - What's love got to do with it? The emotional side of serodiscordant
      relationships.

PMID- 17526107
TI  - HIV and cancer study update. AIDS Malignancy Consortium open next major HIV
      lymphoma trial.

PMID- 17526109
TI  - 14th annual retrovirus conference (CROI). New drugs at CROI: the four musketeers.
      New drugs new targets, new hope.

PMID- 17526110
TI  - 14th annual retrovirus conference (CROI). Conference round-up. New lipo drug,
      rapid testing, and more news from CROI.

PMID- 17526111
TI  - 14th annual retrovirus conference (CROI). HIV prevention update. Some bad news,
      some good news.

PMID- 17526112
TI  - 14th annual retrovirus conference (CROI).  CROI vaccine update. Several HIV
      vaccine trials testing efficacy are underway.

PMID- 17526113
TI  - 14th annual retrovirus conference (CROI). Astounding choice in breastfeeding:
      infection or death.

PMID- 17526114
TI  - 14th annual retrovirus conference (CROI). One-on-one with Joseph J. Eron, MD.
      Interview by Jeff Berry.

PMID- 17526115
TI  - The K-11 Unit. Teaching--and learning--behind bars.

PMID- 17526116
TI  - In honor of Joshua. A family uses their son's legacy to create scholarship money
      for others with HIV.

PMID- 17526118
TI  - A new approach: immune-based treatments against HIV.

PMID- 17526117
TI  - Demystifying MRSA. Drug-resistant bacteria threatens HIV community.

PMID- 17526119
TI  - A systematic review on the   application of pharmacoepidemiology   in assessing  
      prescription drug-related   adverse events in pediatrics.
AB  - OBJECTIVES: To conduct a systematic review of recent case-control and cohort
      studies in assessing adverse drug events (ADEs) among pediatric patients aged
      between 0 and 18 years; to establish strengths and limitations of
      pharmacoepidemiology when applied in evaluating pediatric drug safety; and to
      identify areas of pediatric drug safety that may be suitable for future
      pharmacoepidemiological investigations. METHODS: A PubMed search was conducted
      using a list of keywords representing drugs, adverse drug events, case control
      and cohort studies, and pediatric population. Selection criteria were used to
      extract relevant studies published from 1/1 2000 to 7/1 2006. RESULTS: Twenty
      seven studies met our criteria. Of them, 12 used a prospective cohort design. The
      others were either case-control (seven) or retrospective cohort (eight) studies,
      based on the analysis of existing databases. More than half of the studies
      included more than 500 subjects. Inclusion and exclusion criteria for
      participants in these studies were generally not very stringent. The subjects
      closely resembled patients in the real-world settings. The length of study follow
      up ranged from 1 day to 40 years. In eight studies, the length of follow-up
      surpassed 5 years. Potential confounding factors were taken into consideration in
      all of the studies. But the database-based studies generally failed to control
      for some important clinical variables such as disease severity. Misclassification
      of drug exposures also occurred in some of these studies. CONCLUSIONS: Despite
      some limitations, pharmacoepidemiology proves to be useful for assessing ADEs in
      pediatrics. With appropriate study design, this methodology can bolster our
      understanding about the safety of pediatric drug use. Several areas of pediatric
      drug safety may especially be suitable for future pharmacoepidemiological
      investigations. These areas include the safety of polypharmacy, long-term drug
      effects, and off-label drug use.

PMID- 17526120
TI  - Meeting of the immunization Strategic Advisory Group of Experts, April 2007-
      conclusions and recommendations.

PMID- 17526121
TI  - Revised BCG vaccination guidelines for infants at risk for HIV infection.

PMID- 17526122
TI  - Certified nurse-midwife.

PMID- 17526123
TI  - Consensus statement on mandatory registration of clinical trials.

PMID- 17526124
TI  - Chiropractor.

PMID- 17526125
TI  - Nephrology.

PMID- 17526126
TI  - Hospitalist.

PMID- 17526127
TI  - Rheumatology.

PMID- 17526128
TI  - Intraoperative neurophysiological monitoring and interpretation.

PMID- 17526129
TI  - Practice paper of the American dietetic association: nutrient density: meeting
      nutrient goals within calorie needs.

PMID- 17526130
TI  - No gloves?

PMID- 17526131
TI  - [A case report of epiglottic angiomyolipoma. ].

PMID- 17526132
TI  - Edinburgh and its role in the foundation of Sydney Medical School.
AB  - In 1882, Thomas Anderson Stuart (1856-1920) was appointed as Foundation Professor
      of Physiology and Anatomy at the University of Sydney. At the time he was
      Assistant-Professor of Physiology in the University of Edinburgh. He initiated
      the building of the Sydney Medical School in Scottish Tudor Gothic style. He
      attracted notable figures to Sydney Medical School, such as Dr Robert Scot
      Skirving. The original medical school (now the Anderson Stuart Building)
      continues today as the pre-clinical medical school of the University of Sydney.
      Its stained glass windows and many busts of distinguished figures in the history
      of medicine are a constant reminder of the history of medicine. The building with
      its gothic architecture and echoes of northern Britain has given generations of
      Sydney medical students a powerful message, that they were part of an ancient and
      noble profession. The recruitment of Edinburgh academics to Sydney ended with
      Professor CG Lambie who retired in 1956. The 1950s were a watershed between the
      Edinburgh heritage and the Australian future.

PMID- 17526133
TI  - James Watson, MD, LRCSE--an Edinburgh-trained physician and surgeon in
      northeastern China 1865-1884.
AB  - Much has been written about medical missionaries in China, but not much has been
      published about other Western doctors who practiced there in the nineteenth
      century. James Watson of the Imperial Chinese Maritime Customs Service, the first
      Western doctor to practice in northeastern China, was an Edinburgh medical
      graduate and served in Newchwang, from 1865-1884. He then returned to practice in
      Britain, where he died in 1926.

PMID- 17526134
TI  - Solanaceae III: henbane, hags and Hawley Harvey Crippen.
AB  - Hyoscyamus, the henbane, is one of the drugs of the ancients. Initially used both
      as a poison and narcotic, it was widely adopted by witches, wizards and
      soothsayers as a component of their hallucinatory and flying ointments. It was
      also used by notorious poisoners such as Madame Voisin in France. Eventually, in
      the nineteenth century its active principle was isolated by Ladenburg and called
      l-hyoscine. It proved to be a tropane alkaloid very similar to atropine. These
      two alkaloids proved to be very important in the study of the parasympathetic
      component of the autonomic nervous system, and together with physostigmine,
      allowed the major neurotransmitter acetylcholine to be isolated and its
      mechanisms of action to be characterised. The Crippen murder case in 1910 gave
      hyoscine further fame, indeed, notoriety. The unassuming homeopathic doctor
      murdered his wife with the alkaloid and then decamped for Canada with his
      mistress Ethel Le Neve. The case became a worldwide sensation for several
      reasons: the arrest of the fugitive couple by wireless telegraphy (Marconigram)
      and the extensive chemical and histological evidence presented by Willcox and
      Spilsbury. Some authorities claim that this was the beginning of the science of
      forensic medicine in Britain. Hyoscine is now hardly ever used in modern
      therapeutics but its history from antiquity to the witches and on to Dr Crippen
      is both bizarre and fascinating.

PMID- 17526135
TI  - Eponymous doctors associated with Edinburgh, Part 2--David Bruce, John Cheyne,
      William Stokes, Alexander Monro Secundus, Joseph Gamgee.
AB  - This, the second in a three-paper series with this title, looks at famous doctors
      who trained in Edinburgh and their eponyms. With one possible exception, none
      seems to have sought the eponym, nor awarded it to themselves, nor used it for
      self-promotion. Unlike those in the first paper, all eponyms in this paper are
      still in use and their brevity is in contrast to the lengthy description needed
      if the eponym is not used. Examples are Cheyne-Stokes respiration, Stokes-Adam
      attacks, Brucellosis and Gamgee dressing. Monro Secundus is included because of
      his vehement defence of his professional reputation and research findings when he
      suspected others of trying to detract credit from him, a characteristic seldom
      reported for the others.

PMID- 17526136
TI  - Cats are not small dogs: the emergence of feline medicine.
AB  - Cats have finally garnered the attention they deserve in veterinary medicine,
      however, there is still much to learn about this unique species and new
      challenges surface daily. For example, at the time of writing, avian influenza in
      cats is being closely monitored by world veterinary and health officials.
      Controversial topics, such as how to manage the homeless cat population,
      declawing, and cloning will continue to spark active debate. However, the future
      appears promising for cats as more veterinarians, researchers, and organizations
      increase their focus on felines.

PMID- 17526137
TI  - Milk as a vector of transmission of bovine tuberculosis to humans in Spain: a
      historical perspective.
AB  - As was the case with meat, the detection of the tuberculosis bacterium in cattle
      resulted in the attribution of an important role to milk in human tuberculosis
      infection. However, the case of milk had a more serious impact with graver
      consequences than did meat. In effect, milk was the principal foodstuff by means
      of which tuberculosis was passed from cattle to humans-indeed it could be said
      that it was the only effective vector that carried the bovine bacterium to the
      human organism. In light of this information, this article makes the case that
      milk acted as the most common means of transmission of bovine tuberculosis to
      humans, taking particular note of the problem of the hygienic milk supply in
      Spain.

PMID- 17526138
TI  - The age of veterinary specialization.

PMID- 17526139
TI  - How I became the first Filipino-American county veterinarian in the United
      States.

PMID- 17526140
TI  - The anatomical models of La Specola: production, uses, and reception.
AB  - Since its foundation in the late eighteenth century, the Royal Museum of Physics
      and Natural History (La Specola) in Florence was famous for its anatomical models
      in wax. This paper reconstructs multiple meanings of the models by focusing on
      practices of model production and model use, and by situating the models'
      reception within their institutional and cultural context.

PMID- 17526141
TI  - Racialized bodies.

PMID- 17526142
TI  - [Jacques Clarion (1776-1844), professor of l'Ecole de pharmacie de Paris].
AB  - Engaged in military campaigns from 1793 to 1797, he then studied medicine in
      Paris, as well as pharmacy, specialised in chemistry and botany. Supported by
      Deyeux and Corvisart, he was nominated as pharmacist of the emperor. From 1819 to
      1844, he taught botany at the School of pharmacy of Paris. In 1823, the authority
      gave him a second chair for the medical botany at the Faculty of medicine, but
      after the 1830 revolution, he was dismissed. He mainly worked in taxonomy,
      contributing to several publications with Palisot and de Candolle for
      Graminaceae. He was a member of the academy of medicine.

PMID- 17526143
TI  - [Where it is shown that a quarrel about precedence can lead to the Holy Bible].
AB  - The custom to print a "synthesis", for the last part of the mastership
      examination, the "chef d'oeuvre" was established in most of French towns. Kind of
      printed programme, the "synthesis" was a sheet of paper, of poster size. It
      listed the practicals to perform and the members of the jury, etc. The listing of
      the apothecaries participating in the jury used to be accompanied by elogious
      formulations i.e. "celeberrimo coet-cui pharmacoporum". The physicians immeditely
      reacted. How was it possible? Such elogious terms should be used for medicine
      doctors only! Not for apothecaries! Various printed arguments were exchanged and
      a tumultuous process took place. A judgement occured on December 14 1656: Such
      terms of Honour should be avoided in the future. During this judiciary episode,
      Latin citations from "Ecclesistics, 38" were exchanged. This ridiculous quarell
      rised nevertheless some serious questions. Didn't the translation of the Bible in
      modern languages contain some indaquancies concerning the people in charge of
      preparing and dispensing the medicines? A study of original Greek texts showed
      that it was the case.

PMID- 17526144
TI  - [A XVIth century journeyman apothecar in Montpellier: Jean Magnol (1562-1632)].
AB  - J. Magnol came from Ardeche to Montpellier to learn how to be apothecary grocer.
      He is characteristics of the transition between the Middle-Ages statutes and
      Renaissance ones (1572/1598) in a city famous for its school of medicine. For
      thirteen (13) years he worked as a journeyman apothecary was like a drysalter
      grocer. But the 1572 statutes due to king Henry IV (the fourth), having force of
      law, changed the trade into an art, as highly regarded as the legal profession.
      Long before the 1777 nationwide statutes due to king Louis XIV (the fourteenth).
      To become a master, Magnol had to give four masterpieces, the formulas of which
      can be found in the new pharmacopoeia written by the medicine chancellor: "the
      pharmacopoea Monspeliensis" an alternative to the ancient one by Nicolas de
      Salerne. The pratical experiments were carried out by those famous apothecary
      masters who made up the 1572 statutes. Jean Magnol is Pierre Magnol's ancestor
      (1638-1715), the famous botanist whom Carl Linne dedicated the magnolia genus to.

PMID- 17526145
TI  - [One place, a lot of people. The apothecary companions in Montpellier between
      1574 and 1654].
AB  - Since Middle Age, a lot of apothecary students come in Montpellier for working
      with apothecary masters and for hearing the physician's lessons. After 1574 each
      companion put on a register his name and surname, birth town, arrival date, the
      shop where he is working and the names of examiners before admission. They arrive
      from all the French countries and also European one. Between 1574 and 1654 the
      stream of students depends of the local history and specially of the religious
      disputes.

PMID- 17526146
TI  - [1960-1970 period: pharmaceutical advertisements in France as seen by a general
      practitioner in the Parisian region].
AB  - Pharmaceutical publicity material is a inexhaustible source of ressources and
      marvel. Imagination of publicists in order to get the attention on those
      "ephemera" was unlimited, especially in the 1960-1970 period where regulations
      were still limited and techniques were able to produce relatively cheap well
      printed documents. Pierre Lordez, Maurice Bouvet's son-in-law and general
      practitionner, collected a large part of those documents sent by pharmaceutical
      firms to promote the features of their products and mainly to help physicians
      memorizing the name of their drug specialities. This sampling allows us to
      discover a few aspects of those often unique creations used to bring the
      attention of physicians. Very different subjects were considered that can be
      gathered in three groups: sightseeing and geography; works of art; and finally
      general knowledge that is a way to know more about "the writing through out
      history" as well as "piece of period taps", as exemples. Those advertising
      documents were considered at that time as essentiel by industry but were more or
      less well accepted by physicians that received it. Such documents were probably
      efficient to help sell some products and are in any event a good account of the
      bygone days where it was still feasible to send huge amount of "information"
      documents to physicians for the promotion of pharmaceutical products.

PMID- 17526147
TI  - [Homeopathy and philosophy].
AB  - We are studying here the philosophical evolution of the homeopathy's inventor,
      Hahnemann, and the impact of philosophy on the foundation of his doctrine. As far
      back as 1777 he was, by studying medicine, introduced to animism through two
      critical Stahl's followers, Platner et Whytt, and to the vitalism of
      Montpellier's faculty. To found his theory he used the concept of "reaction" of
      living body on the body acting on it, that we can find as well in the nervous
      theory of animists as by vitalists like Hufeland, or by more mecanists thinkers
      like Haller and Cullen, and that corresponds to different representations of
      Nature medicatrix. As far back as 1801 Hahnemann imagined some morbid causes and
      medicinal actions as dynamic and immateriel. He will finally conceive the living
      being in the same way than the vitalists of Montpellier's school, and will adopt,
      from the Organon's second edition (1819), an immaterial conception of vital
      force. Nevertheless he distinguishs himself of this school by supporting from the
      same time the dynamic and immateriel nature of every morbid cause. His doctrine
      then became more and more spiritualistic and incoherent enough because his
      recognizing of something immateriel and sprirituel into the matter itself, even
      out of a living being, which makes us also suppose any esoteric or theosophical
      sources or influences on his doctrine.

PMID- 17526148
TI  - Francis Crick.

PMID- 17526149
TI  - [Physician Emile Littre, French translator and publisher of Hippocrates].
AB  - To-day, the French author and scholar Emile Littre (1801-1881) is best known as
      the founder of a widely used dictionary of the French language. He was one of the
      most diligent French authors in the nineteenth century and had a huge knowledge
      of modern and ancient languages, medicine, science, history, and philosophy.
      Apart from the dictionary, his most impressive work was the edition and
      translation of the complete collection of the Hippocratic writings (1839-61). The
      translation was meant to serve as a textbook for French doctors, but the rapid
      development in medicine made it obsolete in that respect before it was completed.
      Instead it is now a philological and historical monument. Littre also published a
      large number of books and articles on positivism, history, politics, philology,
      and medicine. He was politically active as supporter of the French republic
      during the periods of monarchy and was elected lifelong senator of the French
      National Assembly after the 1870-71 war. He was elected member of the French
      Academy in spite of intense opposition from the Roman Catholic Church. He was an
      atheist, but was baptised on his deathbed by his wife. His edition of the
      Hippocratic writings still remains the only complete collection in Greek and a
      modern language.

PMID- 17526150
TI  - ["Never at rest--always on the move"--Professor, Surgeon Peter Kisby Moller (1849
      1940)'s diaries from study tours to London and Paris in 1876 and to Berlin in
      1890].
AB  - In the years 1926-28, after his retirement in 1921 from the post of professor of
      surgery at Odense Hospital, Peter Kisby Moller (1847-1940) wrote his
      autobiography. He dedicated the biography to his four sons, three of whom were
      medical doctors. He based the autobiography on diaries written daily in a neat
      hand ever since childhood. As a newly qualified medical doctor at the age of 29
      years, Peter Kisby Moller eagerly devoted himself to the field of surgery, and in
      1876 he embarked on a tour of foreign study. His main goal was to study the
      treatments and results of the great gynaecological surgeons of the time and thus
      increase his store of knowledge of gynaecology. He visited clinics of urology and
      studied the new antiseptic treatment introduced by Lister that significantly
      decreased mortality. He visited many famous London hospitals and observed the
      surgery of sir Spencer Wells who was internationally known for his ovariotomies
      at the time. Later Kisby Moller visited Jules-Emile Pean, Alphonse Guerin, Louis
      Felix Terrier, and Just Lucas-Championniere in Paris. P.K. Moller was
      hardworking, faithful to his patients, and a devout Christian.

PMID- 17526151
TI  - [Building confidence in biological products].
AB  - During the last decades of the 19th century, discoveries in microbiology paved
      the way for health programmes as an integral part of social modernisation. Public
      opinion about the consequences for governmental involvement differed, but in
      Denmark the state's openness to modern medicine encouraged the establishment of
      Statens Serum Institut (SSI) in 1902, initially for the production of anti
      diphtheritic serum. Under its director, Thorvald Madsen (1870-1957), the SSI soon
      acquired a reputation for the high quality of its products and its cutting edge
      research. After qualifying in medicine in 1893, Madsen worked both at the Pasteur
      Institute and with Paul Ehrlich in Frankfurt. During World War I, he served with
      the Red Cross, caring for German, Austrian and Russian prisoners of war. He had
      an extensive and expanding network of international contacts, and he was
      eminently qualified to assume the elected office of President of the League of
      Nations' Health Committee. The Committee served as the 'parliamentary body' of
      the League of Nations Health Organisation (LNHO), and Madsen's hand can be seen
      in much of the work undertaken by the LNHO. The drive to achieve uniform
      standards for biological products related directly to his own as well as the
      SSI's interests and expertise. Undoubtedly, standardization of biological
      products had an immense importance for their distribution, scientifically,
      commercially and therapeutically. Madsen was president of the LNHO's Commission
      on Biological Standardisation from 1924, and during the interwar years, the SSI
      was heavily involved in establishing standards for biological products such as
      tuberculin and tetanus antitoxin. Madsen's interests extended to application of
      prevention technologies, and he utilised the opportunities in Denmark to further
      their use, notably in the case of tuberculosis. The introduction of the BCG
      vaccine promised a solution to the TB problem, but the Lubeck disaster generated
      a widespread reaction against the vaccine. Sponsorship from the Rockefeller
      Foundation led to close investigation of TB incidence in Denmark, and eventually
      to the offer of vaccination of tuberculin-negative Danes. The programme provided
      a foundation for later UNICEF and WHO eradication policies. The paper throws
      light on how local cultures and experience, and personal dedication, shaped the
      policies developed by the interwar international movement.

PMID- 17526152
TI  - [The road to biography: Emil Cold (1865-1953), the physician and the man in his
      time and his place].
AB  - This is a personal account of the author's search for primary sources of a
      biography of Emil Cold (1865-1953), a physician living and working in Esbjerg,
      Denmark. The work on the biography spanned several years of research, tracking
      down archives in soiled, pigeon-infested attics and dusty magazines, reading
      through local newspapers and union pamphlets, interviewing retired nurses and
      doctors, and establishing very inspiring contacts to the descendants of the Cold,
      Finsen and Lyngbye families.

PMID- 17526153
TI  - [Note from the twilight zone of medical history].
AB  - In the reorganization of The Royal Medical Society in Copenhagen in 1845,
      statistics gained a vital role in the activities of the society. Although
      physicians followed the ill-defined approach to statistics that was popular at
      the time, they also contributed to the development and refinement of the modern
      science of statistics. Contrary to the concept of statistics in use at the
      beginning of the 1840's, medicine was driven by much more concrete questions of
      disease. Thus, the earliest use of modern numerical statistics in Denmark was
      found within the medical community. Yet, the use and development of statistics
      generated the modern approach to definitions of disease that we now debate within
      the history and philosophy of medicine.

PMID- 17526154
TI  - [On the history of injection].
AB  - Although the effect of snake bites and poisoned arrows was known from ancient
      time, the development of the syringe and the needle lasted several centuries.
      Forms of intravenous injection and infusion are clearly documented in the 1650s.
      Sir Christopher Wren used a syringe made of animal bladder fixed to a goose quill
      to inject wine and opium into the veins of dogs. J.D. Major from Kiel and J.S.
      Elsholtz from Berlin probably were the first to deliberately administer
      intravenous injections to people in the 1660s. However, these early injections
      were not successful and injections did not come into fashion again until the
      latter part of the 1800s. Forerunners of subcutaneous administration were either
      the introduction of the drug under the epidermis by means of a vaccination-lancet
      or the application of a vesicant to remove the epidermis, after which the drug
      was applied to the denuded cutis. Lafargue, Lembert and Lesieur described these
      methods in the first half of the 1800s, and the methods continued to be of use in
      the second part of the century until the advent of subcutaneous injection.
      Alexander Wood of Edinburgh and Charles-Gabriel Pravaz from Lyon are known
      commonly as the inventors of the syringe for subcutaneous injection, but other
      pioneers such as Taylor, Washington and Rynd had already begun this form of
      administration. Increased use, safety and accuracy were accomplished by the
      progressive steps introduced by Wood, Pravaz and Luer. Thus, the syringe of Luer
      was fitted for aseptic heating, and a sharp needle readily perforated the skin.
      Sterilization by heating in an autoclave was developed by Pasteur, Chamberland
      and Koch, after managing aseptic conditions by the addition of preservatives such
      as carbolic acid. A safe method for the storage of sterile injectates was
      provided by Limousin's ampoule from 1886, and later by the introduction of multi
      dose containers. The evolution of the syringe and its needle continues with the
      introduction of transdermal drug delivery by micron-scale needles and monitored
      drug delivery.

PMID- 17526155
TI  - [From the bath- and massage to the sports clinic--the Rheumatological Department
      of Bispebjerg Hospital 1913-2006].
AB  - At the turn of the previous century, the number of inhabitants in the City of
      Copenhagen increased greatly. A new large hospital, Bispebjerg Hospital, stood
      ready in 1913. At the time, access to light, fresh air, and open spaces was
      considered to be important factors in the battle against disease. Physical
      treatment such as different forms of bathing, massage, exercise, electricity and
      radioactivity were also much relied upon, and a large building for this treatment
      in the form of a Roman thermal bath was built at the clinic of physical medicine.
      The first head of the clinic, Hans Jansen (1875-1933), was a specialist in
      internal medicine who studied physical treatments for a wide range of diseases,
      including phototherapy, as a collaborator of the Nobel Prize laureate Niels
      Finsen. Later, Jansen focused on the treatment of rheumatoid arthritis. It was
      left to the internal medicine ward at Bispebjerg Hospital to introduce the first
      effective treatment with the gold compound Sanocrysin during the 1930's. In 1918,
      physical therapy, physiatry (in Danish, fysiurgi), was established as a medical
      speciality in Denmark. The next head of the clinic, from 1933 Knud Aage Rasmussen
      (1897-1976), a specialist in fysiurgi, focused on the treatment of regional and
      general rheumatic pain syndromes. The rehabilitation of patients with different
      diseases by gymnastic exercises had been in use from the start of the clinic, but
      in the late 1940's more emphasis was put on this treatment under the influence of
      impulses from the USA, and as a response to demographic change with an increased
      number of older individuals with physical challenges in the City of Copenhagen. A
      rehabilitation ward was established and together with the clinic of physiotherapy
      formed a new department in 1968 under the leadership of Lone Gjorup (1923-2005).
      At the same time, interest in the treatment of inflammatory rheumatic diseases
      rose after the discovery of glucocorticoids as potent anti-inflammatory
      compounds. The department at Bispebjerg Hospital followed this dual course of
      treatment of inflammatory diseases with new drugs and rehabilitation. Recent new
      technology and interest in sports medicine promoted research in physical training
      in the clinic and eventually gave rise to a separate research and development
      unit devoted to sports medicine.

PMID- 17526156
TI  - [When cochlear implants came to Denmark and the deaf began to hear].
AB  - For several hundreds years, deafness in humans and deaf-mute humans has been a
      challenge to doctors and other therapists. During the last 50 years, it has
      become possible to treat deaf people. The reasons for this success in treatment
      and the introduction of the treatment in Denmark are the topics of this text. To
      make deaf people hear, patients were treated with electricity for more than two
      hundred years,in Denmark as well as other countries. This development depended on
      many important factors for a positive result of the treatment. The first
      operation of a deaf patient in Denmark was performed in Odense. Some years later
      the treatment began at Gentofte Hospital and later at Aarhus City Hospital. The
      start was slow, to some extent because of financial circumstances but also
      because the necessary equipment was not fully developed. There were also
      difficulties with selection of the most suited patients, training of patients,
      resistance against treatment from organisations of the deaf and from conventional
      teachers of the deaf. The problems were solved over a period of some years, and
      the population could soon see and meet patients as celebrities, i.e., previously
      deaf persons who could now use a telephone. More than 600 deaf people have now
      been operated in Denmark. The term deafness has changed its meaning, and probably
      there will no new cases of the deaf-mute in the future.

PMID- 17526157
TI  - [PET in Aarhus: the origins of a laboratory].
AB  - Recent medical history is a new trend among medical historians. The new focus on
      late developments of note to health care providers has inspired me to relate
      certain personal events related to the establishment of a laboratory of positron
      emission tomography in a remote city of a small country far away. The record may
      be appropriate because the laboratory celebrated its 10th anniversary in 2003.
      The laboratory is the home of an advanced technology with special needs in terms
      of space, installations and staff. The technology rests on a combination of
      random discoveries and goal-directed inventions that include the discovery of
      positrons, the invention of the cyclotron, the development of computerized
      analysis of huge data sets, insight into the biochemistry of organs and the quest
      for understanding of the pathology of specific diseases. U.S. researchers played
      unique roles in the three former areas, while Danish researchers made important
      contributions to the latter two areas.

PMID- 17526159
TI  - David Bodian.

PMID- 17526158
TI  - The origin and virulence of the 1918 "Spanish" influenza virus.
AB  - The "Spanish" influenza pandemic of 1918-19 caused acute illness in 25-30 percent
      of the world's population and resulted in the death of up to an estimated 40
      million people. Using fixed and frozen lung tissue of 1918 influenza victims, the
      complete genomic sequence of the 1918 influenza virus has been deduced. Sequence
      and phylogenetic analysis of the completed 1918 influenza virus genes shows them
      to be the most avian-like among the mammalian-adapted viruses. This finding
      supports the hypotheses that (1) the pandemic virus contains genes derived from
      avian-like influenza virus strains and that (2) the 1918 virus is the common
      ancestor of human and classical swine H1N1 influenza viruses. The relationship of
      the 1918 virus with avian influenza viruses is further supported by recent work
      in which the 1918 hemagglutinin (HA) protein crystal structure was resolved.
      Neither the 1918 hemagglutinin (HA) nor the neuraminidase (NA) genes possess
      mutations known to increase tissue tropicity that account for the virulence of
      other influenza virus strains like A/WSN/33 or the highly pathogenic avian
      influenza H5 or H7 viruses. Using reverse genetics approaches, influenza virus
      constructs containing the 1918 HA and NA on a modern human influenza virus
      background were lethal in mice. The complete 1918 virus was even more virulent in
      mice. The genotypic basis of this virulence has not yet been elucidated. The
      complete sequence of the non-structural (NS) gene segment of the 1918 virus was
      deduced and also tested for the hypothesis that enhanced virulence in 1918 could
      have been due to type I interferon inhibition by the NS1 protein. Results from
      these experiments suggest that in human cells the 1918 NS1 is a very effective
      interferon antagonist, but the 1918 NS1 gene does not have the amino acid change
      that correlates with virulence in the H5N1 virus strains identified in 1997 in
      Hong Kong. Sequence analysis of the 1918 pandemic influenza virus is allowing us
      to test hypotheses as to the origin and virulence of this strain. This
      information should help elucidate how pandemic influenza virus strains emerge and
      what genetic features contribute to virulence in humans.

PMID- 17526160
TI  - When do scientists become entrepreneurs? The social structural antecedents of
      commercial activity in the academic life sciences.
AB  - The authors examine the conditions prompting university-employed life scientists
      to become entrepreneurs, defined to occur when a scientist (1) founds a
      biotechnology company, or (2) joins the scientific advisory board of a new
      biotechnology firm. This study draws on theories of social influence,
      socialization, and status dynamics to examine how proximity to colleagues in
      commercial science influences individuals' propensity to transition to
      entrepreneurship. To expose the mechanisms at work, this study also assesses how
      proximity effects change over time as for-profit science diffuses through the
      academy. Using adjusted proportional hazards models to analyze case-cohort data,
      the authors find evidence that the orientation toward commercial science of
      individuals' colleagues and coauthors, as well as a number of other workplace
      attributes, significantly influences scientists' hazards of transitioning to for
      profit science.

PMID- 17526161
TI  - [Strengthening research of traditional Chinese medicine on fatty liver].

PMID- 17526162
TI  - [Prevention and treatment of fatty liver by integrative medicine].

PMID- 17526163
TI  - [Fatty liver--a disease shouldn't be ignored].

PMID- 17526164
TI  - [Relationship between HBV-DNA in peripheral blood mononuclear cells and syndrome
      types of TCM in chronic hepatitis B patients].
AB  - OBJECTIVE: To study the relationship between TCM syndrome type and HBV-DNA in
      serum and peripheral blood mononuclear cells (PBMCs) in chronic hepatitis B (CHB)
      patients. METHODS: The serum HBV markers,HBV-DNA levels in serum and PBMCs, were
      quantitatively detected in 220 CHB patients by PCR method, and TCM syndrome type
      of 205 patients were differentiated. RESULTS: Arranged from low to high, the
      percentages of CHB patients with the serum HBV-DNA > or = 1.0 x l0(5) copy/mL
      (high viral loading) in the five syndrome types were as follows: damp-heat
      retention in middle-jiao syndrome (DHRS, 55.2%), blood stasis blocking collateral
      syndrome (BSBC), Gan-Shen yin deficiency syndrome (GSYS), Pi-Shen yang deficiency
      syndrome (PSDS) and Gan stagnation with Pi deficiency syndrome (GSPS, 82.5%), the
      difference was significant between DHRS and GSPS; those with HBV-DNA in PBMCs
      infection were: GSYS (27.3%), DHRS (34.3%), BSBC (53.1%) and GSPS (77.2%). The
      percentage in GSPS was the highest, which was significantly different to that in
      other syndromes. CONCLUSION: Amount of serum HBV-DNA and PBMCs HBV-DNA infection
      has certain correlation with the TCM syndrome type of CHB. The highest percentage
      of patients with HBV-DNA > or = 1.0 x l0(5) copy/mL and PBMCs HBV-DNA infection
      presented in CHB patients of GSPS type. We should pay more attention to
      strengthen genuine qi to eliminate pathogenic factors in treatment of CHB.

PMID- 17526165
TI  - [Effect of spleen-invigorating prescription on dendritic cell function in
      patients with chronic hepatitis B of TCM Pi-deficiency syndrome type].
AB  - OBJECTIVE: To observe the effect of Spleen-invigorating Prescription (SIP) on
      dendritic cell function in patients with chronic hepatitis B. METHODS: A total of
      60 patients with chronic HBV of Pi-deficiency syndrome type were enrolled and
      randomized to 2 groups, 30 in each group. Patients in the control group were
      given intramuscular injection with human interferon alpha 1b, 3 times a week,
      while those in the treated group were given orally with SIP twice a day, the
      therapy lasted for 6 months. Dendritic cells (DCs) were isolated from peripheral
      blood and cultured, then the expression of surface markers, HLA-DR, CD86, CD80,
      CD40, CD14 and CD11c were detected before and after treatment by flow cytometry,
      and the function of DCs was also evaluated by mixed lymphocyte reaction (MLR)
      determination once before treatment and once after treatment. RESULTS: The
      expressions of DCs' surface CD86, CD80, CD40 and CD11c in the treated group were
      higher (P < 0.05, P < 0.01) and the changes of stimulating index, IFN-gamma and
      IL-12 were superior in the treated group to those in the control group (P <
      0.05). CONCLUSIONS: SIP can significantly improve DC's function, so, one of
      mechanisms of SIP in improving clinical efficacy may be the regulation of immune
      function.

PMID- 17526166
TI  - [Clinical observation on auxiliary treatment with suanzaoren decoction for
      chronic severe hepatitis].
AB  - OBJECTIVE: To investigate the curative effect and safety of auxiliary treatment
      with Suanzaoren Decoction (SZRD) on patients with chronic severe hepatitis (CSH).
      METHODS: Sixty patients, with the diagnosis in accordance with the diagnostic
      criterion of CSH, were assigned to the treated group and the control group, 30 in
      each group. Patients in the control group were treated with comprehensive therapy
      including symptomatic supportive treatment, anti-infective therapy and artificial
      liver plasmapheresis etc., while those in the treated group were orally taken
      SZRD additionally. Patients' condition of sleeping and changes of total bilirubin
      (TBIL), prothrombin activity (PTA), tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1 (IL-1) were observed before and after treatment, and the adverse
      reactions were observed as well. RESULTS: The sleeping status were significantly
      improved in the treated group after treatment, and the serum levels of TBIL, TNF
      alpha and IL-1 were significantly decreased. The improvement rate was 66.7%
      (20/30) and significantly higher than that (40.0%, 12/30) in the control group.
      CONCLUSION: SZRD can significantly improve the sleeping status of CSH patients,
      alleviate the hepato-cellular injury by inflammatory cytokines and without
      obvious adverse reaction.

PMID- 17526167
TI  - [Quality appraisal of systematic reviews or meta-analysis on traditional Chinese
      medicine published in Chinese journals].
AB  - OBJECTIVE: To critically assess the quality of literature about systematic review
      or meta-analysis on traditional Chinese medicine (TCM) published in Chinese
      journals. METHODS: Electronic searches in CNKI, VIP and Wanfang data-base were
      conducted to retrieve the systematic reviews or meta-analysis reports on TCM,
      including herbal medicine, needling, acupuncture and moxibustion, as well as
      integrative medicine, they were identified and extracted according to the 18
      items of QUOROM (quality of reporting of meta-analyses) Statement and relative
      information. The appraisal was made taking the indexes mainly including
      objectives, source of data, methods of data extraction, quality assessment of the
      included studies, measurement data synthesis, etc. RESULTS: Eighty-two systematic
      reviews were identified, except 6 reviews were excluded for repeatedly published
      or didn't comply with the enrolled criterion, 76 reviews concerning 51 kinds of
      diseases were enrolled for appraisal. Among them, 70 reviews evaluated the
      efficacy of TCM, mainly on Chinese herbs and 9 on acupuncture and moxibustion. In
      majority of the reviews, randomised controlled trials were included and the data
      resources were described, but in 26 reviews only the Chinese databases were
      searched and the description about data extraction and analysis method were too
      simple; and 70% of reviews assessed the quality of the included studies; none
      used flow chart to express the process of selection, inclusion and exclusion of
      studies. CONCLUSIONS: Few reviews or Meta-analysis reports reached the
      international standard and there is insufficient description of methodology for
      conducting systematic reviews, so it is hardly to be repeated. The authors
      suggested that advanced methodological training is necessary for reviewers.

PMID- 17526168
TI  - [Clinical observation on effect of acupuncture in treating diabetic peripheral
      neuropathy].
AB  - OBJECTIVE: To observe the effect of acupuncture in treating diabetic peripheral
      neuropathy (DPN). METHODS: Sixty patients with DPN were randomly assigned to the
      acupuncture treated group and the control group, 30 in each group. Besides basic
      treatment, patients were treated additionally with acupuncture and orally
      administration of Methycbal (Mecolbalamin) for 8 weeks respectively. Changes of
      symptoms, blood glucose, HbA1c, whole blood and plasma viscosity, the nerve
      conduction velocity (NCV) of sensory and motor nerves before and after treatment
      were observed. RESULTS: Acupuncture can ameliorate symptoms and signs of the
      nervous system, decrease whole blood and plasma viscosity, and improve the NCV of
      sensory and motor nerves in patients with DPN. CONCLUSION: The effect of
      acupuncture in treating DPN is definite.

PMID- 17526169
TI  - [Effect of Liuwei Dihuang soft capsule and Ginkgo leaf tablet on serum regulated
      upon activation, normal T cell expressed and secreted in patients with diabetes
      mellitus type 2].
AB  - OBJECTIVE: To investigate the effect of Liuwei Dihuang Soft Capsule(LDSC) and
      Ginkgo Leaf Tablet (GLT) on serum regulated upon activation, normal T cell
      expressed and secreted (RANTES) in the patients with diabetes mellitus type 2
      (DM2). METHODS: Forty patients with early stage DM2 were randomly assigned to two
      groups, 20 in each group. Based on the conventional treatment with hypoglycemic
      agents, patients in the treated group were treated with LDSC plus GLT
      additionally, and those in the placebo group with placebo for 6 months,
      respectively. The levels of serum RANTES, blood glucose, blood lipids and
      glycosylated hemoglobin, as well as micro-content of albumin in urine were
      measured before and after treatment. RESULTS: In the treated group, the serum
      level of RANTES decreased significantly after treatment, and it was significantly
      lower as compared with that in the control group (P < 0.05). CONCLUSIONS: LDSC
      and GLT can decrease serum RANTES level in patients with DM2. They play a
      preventive and therapeutic role on diabetic complications by their anti
      inflammatory effect.

PMID- 17526170
TI  - [Study on Modified Xiaoyao Decoction combining Clomipramine treating depression].
AB  - OBJECTIVE: To observe the efficacy of Modified Xiaoyao Decoction (MXD) combining
      clomipramine in treatment of depression. METHODS: One hundred and five depression
      patients were randomly assigned to two groups. The treated group (53 patients),
      all were differentiated as Gan-qi stagnation syndrome type and treated with MXD
      combining clomipramine 25-50 mg/d. The control group (52 patients) treated with
      clomipramine 75-225 mg/d alone. The treatment lasted for 8 weeks in both groups.
      Scores of depression was assessed with Hamilton Depression Scale (HAMD) before
      treatment and at the 2nd, 4th, 8th week of the treatment, efficacy and adverse
      reactions were evaluated with Global Impression of Change (CGI) and Treatment
      Emergent Symptom Scale (TESS) respectively. RESULTS: After treatment the scores
      in both groups were significantly different from those before treatment (P <
      0.01), but no significant difference was found between the two groups (P > 0.05).
      Main adverse reactions were dry mouth, constipation in the treated group, much
      less than those in the control group, which were mainly dry mouth, constipation,
      dizziness, insomnia, blurred vision and prolonged Q-T interval (P < 0.01).
      CONCLUSION: MXD combining clomipramine has the efficacy on depression similar to
      clomipramine, but has less adverse reactions.

PMID- 17526171
TI  - [Effect of saikosaponin-d on rat's glomerular mesangial cell proliferation and
      extracellular matrix hyperplasia in vitro].
AB  - OBJECTIVE: To investigate the effects of saikosaponin-d (SSd) on glomerular
      mesangial cells (MCs) proliferation and hyperplastic extracellular matrix (ECM)
      induced by lipopolysaccharide (LPS) to provide experimental proof for its use in
      prevention and treatment of glomerulosclerosis. METHODS: Rat's MCs were
      cultivated and identified. The cultured MCs were stimulated by LPS and incubated
      with different concentrations of SSd. Cell proliferation was determined by MTT
      assay, LDH assay and flow cytometry, respectively. Type IV collagen (Col IV),
      fibronectin (FN) and transforming growth factor beta1 (TGF-beta1) in the
      conditioned medium were measured by ELISA. The expressions of cyclin-dependent
      kinase 4 (CDK4), c-Jun and c-Fos were detected by immunohistochemistry. RESULTS:
      After treated by SSd, MC proliferation was inhibited, cells in G0/G1 phase
      increased, and apoptosis induced. Moreover, secretion of Col IV, FN and TGF-beta1
      and the expressions of CDK4, c-Jun and c-Fos in MC were inhibited. CONCLUSION:
      The inhibitory action of SSd on glomerulosclerosis was realized through
      inhibiting the expressions of CDK4, c-J un and c-Fos.

PMID- 17526172
TI  - [Effect of tongshenluo capsule on the components of extracellular matrix and
      their metabolism in kidney of rats with diabetic nephropathy].
AB  - OBJECTIVE: To investigate the effect of Tongshenluo Capsule (TSL) on the
      components of extracellular matrix (ECM) and their metabolism in kidney of rats
      with diabetic nephropathy (DN), and to explore its mechanism of kidney
      protecting. METHODS: The DN model rats established by one side nephrectomy and
      intraperitoneal injection of streptozotocin were randomly divided into 5 groups,
      the sham-operation group, the model group, the Valsartan group, the Gliquidon
      group, and the TSL group, 10 in each group. Levels of fasting blood glucose (FBG)
      and 24-h urinary micro-content of albumin (24 h mAlb) were determined
      dynamically; the serum glycosyl hemoglobin (HbA1c)was determined after the last
      medication; the ultrastructural changes of kidney were observed by transmission
      electron microscope; the expressions of collagen IV (IV-C), fibronctin (FN),
      laminin(LN), and the ECM metabolism influencing factors, including MMP-2, tissue
      inhibitor of metalloproteinase (TIMP-2), transfer growth factor-beta1 (TGF-beta1)
      in renal tissue were detected by immunohistological chemistry and image
      collecting analytical system. Results TSL could decrease the levels of FBG,
      HbA1c, 24 h mAlb (P < 0.05 or P < 0.01), ameliorate the thickness of glomerular
      basement membrane (GBM), decrease the components of ECM, down-regulate TGF-beta1
      and TIMP-2 expression, and up-regulate MMP-2 expression (P < 0.05 or P < 0.01).
      CONCLUSION: TSL plays a role of kidney protection by decreasing the ECM
      components expression and regulate ECM metabolism.

PMID- 17526173
TI  - [Effect of panax quinquefolius saponin on angiogenesis and expressions of VEGF
      and bFGF in myocardium of rats with acute myocardial infarction].
AB  - OBJECTIVE: To study the effect of Panax quinquefolius Saponin (PQS), an
      extraction from stem and leaf of American ginseng, on vascular regeneration in
      infarcted area, and expressions of vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF) in myocardium of rats with acute myocardial
      infarction (AMI). METHODS: Fifty male Wistar rats were established into AMI model
      successfully and randomly divided into 5 groups equally, i.e. the model group,
      the high, middle and low dose PQS groups and the metoprolol group. They were
      treated with saline, different doses of PQS (54 mg/kg x d, 27 mg/kg x d, 13.5
      mg/kg x d)and metoprolol (4.5 mg/kg x d) respectively, by gavage once a day for
      14 days. Besides, a sham operated group and a normal control group were set up
      for control with 10 rats in each group. All rats were killed on the 15th day. Six
      samples of heart were chosen from each group for examining expressions of VEGF,
      bFGF and the VIII coagulation factor under light microscopy by
      immunohistochemical staining, and the quantitative analysis on positive
      responsive intensity of VEGF and bFGF was conducted on the other 4 heart samples
      using the image analysing system, then mean micro-vessel density (MMVD) was
      calculated. RESULTS: The expressions of VEGF and MMVD were higher in the high and
      the middle dose PQS groups than those in the model group (P < 0.05) and the
      expression of bFGF was higher in the three PQS groups than that in the model
      group (P < 0.05). CONCLUSION: PQS can protect myocardium from ischemic injury in
      rats after AMI by way of promoting angiogenesis in the infarcted or ischemic area
      of myocardium and up-regulating expressions of VEGF and bFGF in myocardial cells.

PMID- 17526174
TI  - [Effect of Wenmaitong on adhesion of monocytes to vascular endothelial cell
      induced by hyperlipidemic serum].
AB  - OBJECTIVE: To study the effect of Wenmaitong (WMT) and its disassembled formulas
      on the adhesion of monocytes to endothelial cells induced by hyperlipidemic serum
      to explore the mechanism of WMT on early arteriosclerosis obliterans (ASO).
      METHODS: Serums containing whole WMT and its disassembled formulas, including the
      formula consisted of warming Jing and boosting qi part (Wenjin Yiqi, WY) and that
      of promoting blood circulation part (Huoxue Tongmai, HT), as well as the serum
      contained high concentration of lipids were prepared conventionally,
      respectively. The adhesion of monocytes cell strain THP-1 to human umbilical
      vascular endothelial cells (HUVEC) was determined by rose bengal stain method,
      and ELISA was used to detect expressions of intercellular adhesion molecule (ICAM
      1), vascular cellular adhesion molecule (VCAM-1) and P-selectin on HUVEC surface.
      RESULTS: WMT could inhibit THP-1 to HUVEC adhesion induced by hyperlipidemic
      serum, and down-regulate the expression of ICAM-1, VCAM-1, P-selectin on HUVEC
      surface, the two disassembled formulas could down-regulate different adhesion
      molecules. CONCLUSION: One mechanism of WMT on ASO may be its inhibition on
      arteriosclerosis by way of down-regulating the expression of vascular endothelial
      cells adhesion molecules to decrease the adhesion of monocyte to VEC, therefore
      to inhibit the monocytes migrating into vascular intima to develop foam cells.

PMID- 17526175
TI  - [Experimental study of inhibition of safflower injection on mesenteric
      microvascular motion in rabbits DI].
AB  - OBJECTIVE: To dynamically observe the effect of Safflower Injection (SI) on
      mesenteric microvascular motion in vivo in rabbits, and to explore the effect of
      nitric oxide (NO) in the process to further investigate the action mechanism of
      activating blood to remove stasis of SI. METHODS: Twenty healthy male albino
      rabbits were intraperitoneally injected with urethane for basic anesthesia and
      injected with alpha-chloralose via ear marginal venous to maintain anesthesia,
      spontaneously ventilated via tracheotomy tube, with the in-step record of breath
      and blood pressure. The vasomotion was induced by noradrenaline (NA) in vivo,
      then the changes of vasomotion after injecting SI and N(G)-monomethyl-L-arginine
      (L-NMMA, a NO synthase inhibitor) were measured respectively on a TV monitor
      using a TV camera mounted on the microscope, and the influence of L-NMMA on
      effect of SI was also observed. RESULTS: L-NMMA injection alone can inhibit the
      NA induced vasomotion in vasoconstriction state, while SI injection alone can
      inhibit it in vaso-dilation state. SI could abolish the effect of L-NMMA on
      vasomotion but L-NMMA did not influence the effect of SI on vasomotion.
      CONCLUSION SI can inhibit vasomotion in vaso-dilation status, but its mechanism
      is not mediated by endogenous NO.

PMID- 17526176
TI  - [Effect of Fuzheng Yiliu Granule contained-serum from tumor bearing mice on
      apoptotic rate, free radicals content and mitochondrial membrane potential of
      hepatoma cell lines H22 in vitro].
AB  - OBJECTIVE: To observe the effect of traditional Chinese herbs Fuzheng Yiliu
      Granule (FYG)-contained serum from tumor bearing mice on apoptotic rate, free
      radicals content and mitochondrial membrane potential of hepatoma cell lines H22
      in vitro. METHODS: The effect of FYG drug-serum on apoptosis of hepatoma cell
      line H22 was determined using flow cytometry. The changes of DNA RNA, free
      radicals and mitochondrial membrane potential (delta psi m) in H22 cell were
      detected through laser scanning confocal microscope. RESULTS: FYG-contained serum
      can induce the apoptosis of H22 cell, enhance the free radicals content, and
      reduce the content of DNA RNA and delta psi m of H22 cell in vitro. CONCLUSION:
      The apoptosis of hepatoma cell line H22 induced by FYG is probably correlated to
      the change of free radicals content and delta psi m.

PMID- 17526177
TI  - [Experimental study on effect of Huaxian Decoction treating bleomycin-induced
      pulmonary fibrosis in mice].
AB  - OBJECTIVE: To study the preventive and therapeutic effect of Huaxian Decoction
      (HXD) on bleomycin-induced pulmonary fibrosis in mice by taking treatment of
      ligustrazin and prednisone as controls, for investigate the clinical value and
      possible mechanism in treatment of pulmonary fibrosis by traditional Chinese
      herbs. METHODS: A total of 96 male ICR mice, aged 6 to 8 weeks, were randomly
      divided into 8 groups. Pulmonary fibrosis was induced in the model group by
      intranasal instillation of bleomycin 5 mg/kg. HXD were given via gastrogavage to
      the HXD prevention group and treatment group respectively at 48 h before and 14
      days after they were modeled with the same method, and the groups of ligustrazin
      and prednisone, treatment and prevention, were managed the same as for HXD
      groups, but with ligustazin and prednisone instead of HXD respectively.
      Bronchoalveolar lavage fluid (BALF) and lung tissue of animals were gathered on
      day 28. Cellular ultrastructural changes of lung was examined under electron
      microscope by HE, Masson stain; Content of hydroxyproline (HYP) in lung tissue
      was assessed by acidolysis method; and concentration of transforming growth
      factor-beta1 (TGF-beta1) in BALF was assessed by ELISA. RESULTS: Pulmonary
      coefficient was significantly lower in all the drug intervening groups than that
      in the model group (P < 0.05), improvement on alveolitis and pulmonary fibrosis
      were alsonaged the safter intervention, especially in the HXD prevention group
      (Pinstead < 0.05). HYP content in lung tissue and TGF-beta1 content in BALF
      lowered at the same time. CONCLUSION: Early stage application of HXD can
      alleviate bleomycin-induced alveolitis and pulmonary fibrosis in mice to certain
      degree, suggesting that Chinese herbs with supplementing qi and activating blood
      circulation effect could play a definite preventive action on pulmonary fibrosis,
      and the inhibition on expressions of TGF-beta1 in lung tissues may be one of the
      mechanisms.

PMID- 17526178
TI  - [Clinical observation on effect of compound E-bei ointment in treating plaque
      psoriasis].
AB  - OBJECTIVE: To observe the efficacy oand safety of Compound E-Bei ointment (CEBO)
      in treating plaque psoriasis. METHODS: Adopting block-randomized, open, positive
      Western medicine and placebo parallel group controlled method, a total of 120
      enrolled patients were administered orally with Saoxuan Pill, and randomized into
      three groups respectively treated with external application of CEBO, Daivonex, or
      vehicle control twice a day for 4 weeks. The changes of erythema, infiltration,
      scaly eruption, pruritus and the area of lesion were evaluated, the safety and
      the initiating time of symptom improvement (ITSI) were observed as well. RESULTS:
      Observation on local lesion showed that the scores of erythema, infiltration,
      scaly eruption, pruritus were significantly improved in difference between the
      CEBO group and the Daivonex group (P < 0.01). But in the placebo control group,
      significant improvement was only shown in scaly eruption scores (P < 0.01), so,
      the improvement in skin lesion in the placebo group was significantly inferior to
      that in the other two groups (P < 0.01). The ITSI of pruritus was shorter in CEBO
      group than that in the Daivonex group and the placebo group (P < 0.01), but that
      of other symptoms showed insignificant difference between the CEBO group and the
      Daivonex group, as for comparing in ITSI of erythema, infiltration, scaly
      eruption and pruritus, it was significantly shorter in the CEBO group and
      Daivonex group than that in the placebo group respectively (P < 0.01). The
      occurrence of adverse events in the CEBO group had insignificant difference to
      that in the Daivonex group, but the recurrence rate in the former was
      significantly lower than that in the latter (P < 0.05). CONCLUSION: CEBO can
      effectively improve the symptoms of skin lesion in patients with plaque
      psoriasis, the clinical efficacy is not inferior to that of positive Western
      medicine.

PMID- 17526179
TI  - [Therapeutic effects of acupoint drug-finger pressing on gastroesophageal
      reflux].
AB  - OBJECTIVE: To observe the clinical effects and possible mechanism of acupoint
      drug-finger pressing (ADFP) on gastroesophageal reflux (GER). METHODS: Eighty
      patients were randomly assigned to the treatment group and the control group, 40
      in each group. The treatment group was treated by ADFP on Ganshu (BL18), Danshu
      (BL19), Weishu (BL21) and Pishu (BL20) acupoint of bilateral Foot-taiyang Bladder
      Meridians with pressing and kneading maneuver for 15 min each time, twice per
      day, while the control group was treated with acid-inhibitory and gastrokinetic
      drugs as omeprazole enteric-coated tablets (20 mg, once administration at a 12-h
      interval) and cisapride tablets (10 mg, thrice daily, taken 15 min before meals).
      The treatment course for both was 3 weeks. RESULTS: The symptom score and
      esophageal pressure obviously decreased (P < 0.05), esophageal pressure was
      relieved remarkably (P < 0.05) in both groups after treatment with insignificant
      difference between the groups (P > 0.05). The ratio of 24-h esophageal reflux
      times and total reflux time, the times of reflux lasting for more than 5 min and
      the maximum reflux time were all lowered obviously in all patients after
      treatment, and the improvements was significantly different between the two
      groups (P < 0.05). Upper gastrointestinal endoscopy suggested obvious
      amelioration in esophagitis. The total effective rate was 97.5% in the treatment
      group, significantly higher than that in the control group (80.0%) (P < 0.05).
      And no obvious adverse reaction was found. CONCLUSION: Therapy of ADFP provides a
      new approach for GER treatment with TCM characteristics, prominent effects and
      less adverse reaction, and is easily be accepted by patients, so, it is worthy to
      be generalized.

PMID- 17526180
TI  - [Clinical observation on effect of Jieyu Anshen Decoction combined with
      aripiprazole in treating chronic schizophrenia].
AB  - OBJECTIVE: To explore the efficacy and safety of Jieyu Anshen Decoction (JAD)
      combined with aripiprazole in treating chronic schizophrenia. METHODS: All 100
      patients with chronic schizophrenia diagnosed according to CCMD-3 criteria were
      equally randomly assigned to the study group (treated with JAD combined with
      aripiprazole) and the control group (treated with aripiprazole alone) for 12
      weeks. The efficacy and safety were evaluated by Positive and Negative Syndrome
      Scale (PANSS) and Treatment Emergent Side Effect Scale (TESS). RESULTS: After 12
      weeks of treatment, the clinical efficacy in the study group was significantly
      higher than that in the control group, the PANSS score in the study group was
      significantly decreased with a higher speed and range of decreasing, becoming
      lower than that in the control group at the same period. But the difference
      between the two groups in scores of TESS at corresponding times showed no
      significance. CONCLUSION: JAD combined with aripiprazole has definite effect in
      treating chronic schizophrenia, shows advantages of quickly initiating effect,
      high safety and with no harm for increasing adverse reactions, so it is better
      than using aripiprazole alone.

PMID- 17526181
TI  - [Effect of scalp acupuncture drawing method on motor function in hemiplegic
      patients following cerebral thrombosis at convalescent period].
AB  - OBJECTIVE: To observe the effect of scalp-acupuncture drawing method (SADM) on
      recovering motor function in hemiplegic patients following cerebral thrombosis at
      convalescent period. METHODS: Adopting randomized, single-blinded, controlled
      method, 93 patients suffering from hemiplegia following cerebral thrombosis were
      randomly assigned to 3 groups, 31 in each group. All patients were treated based
      on neurological routine therapy, those in the treated group and the control group
      I were treated respectively with SADM and scalp-acupuncture twirling method
      (SATM) additionally, but for those in the control group II, no additional
      treatment was given. The treatment course for all was 4 weeks. RESULTS: Before
      treatment, there were insignificant difference among 3 groups in the score of
      neural motor function deficits (NFDS) of limbs and activity of daily life (ADL)
      score (P > 0.05). After being treated for 4 weeks, the NFDS was significantly
      lower and in the control group II (P < 0.01, P < 0.05) and the change of the
      scores in the treated group was more than that in the control group I (P < 0.05).
      CONCLUSION: SADM was superior to scalp-acupuncture twisting prove the ADL score
      and motor function of hemiplegia patients following cerebral thrombosis in the
      convalescent stage.

PMID- 17526182
TI  - [Important action of improving adrenocortical function for certain diseases
      recovery].
AB  - It has been found that the hypofunction status of hypothalamus-pituitary-adrenal
      (HPA) axis exists in patients with Shen-yang deficiency syndrome of TCM, also
      presents in most asthma patients. Seasonal attack of asthma can be prevented with
      Shen-tonifying drugs by improving adrenocortical function. Since patients subject
      to long-term glucocorticoids display hypofunction condition of HPA axis, Shen
      tonifying drugs should be helpful to gluocorticoid withdrawal for getting higher
      success rate. Basic researches also indicated that the activating of
      adrenocortical stem cells and promoting regeneration of adrenal cortex is one of
      the mechanisms underlying improvement of adrenocortical function. Series of
      research showed that hypofunction of adrenocortex is the general pathological
      change in some diseases, so, Shen-tonifying drugs act a part in unitarily
      modulating the adrenocortical function, to get the therapeutic effect of both
      regulating the whole and improving the local.

PMID- 17526183
TI  - [Linguistic-cultural differences between Chinese and Western medicine and English
      translation of Chinese medicine].
AB  - This paper explores the influences of linguistic-cultural differences between
      Chinese and Western medicine on the English translation of Chinese medicinal
      terms/literature from such aspects as ideographic, phonetic writings and thinking
      modes, Chinese and Western medical terms, as well as Classic literature of
      Chinese medicine and medical English.

PMID- 17526184
TI  - [How to simplify and shorten the English translation of traditional Chinese
      medicine].
AB  - Aiming at the present tedious English translation of traditional Chinese
      medicine, the author advocates some approaches to simplify it in order to improve
      the readability, communicability and quality of translation.

PMID- 17526185
TI  - [Progress in therapeutic principles and the characteristics of strategies for
      treatment of hypertension and its changes in China].
AB  - To briefly introduce the updated principles for treatment of hypertension by
      reviewing foreign literatures in point of this aspect and its progress. The
      strategies of hypertension treatment in our country experienced the development
      from "non-principles (NP)", "partial principles (PP)" to "full principles (FP)",
      and already realized five conversions, i.e. the conversion from simply depress
      the blood pressure to multi-drugs, multi-targets and multi-pathways comprehensive
      therapy, and put stress on both prevention and treatment. The authors emphasized
      that NP should be rejected completely, and population proportion of PP,
      especially FP used should be elevated in hypertension treatment in the future.

PMID- 17526186
TI  - [Acute lung injury syndrome].

PMID- 17526187
TI  - [The BODE index as a predictor of unfavourable prognosis in chronic obstructive
      pulmonary disease (by the results of a prospective study)].
AB  - AIM: To determine the death risk factors in patients with chronic obstructive
      pulmonary disease (COPD) in the course of a follow-up and to study feasibility of
      BODE index use for prognosis in COPD patients. MATERIAL AND METHODS: A total of
      86 COPD patients were followed up for 3-5 years. The examination included total
      blood count, ECG, estimation of body mass index, external respiration function,
      pulsoxymetry, measurement of dyspnea characteristics by MMRC scale, physical
      activity by a 6-min walk test. Within the follow-up time 19 patients died, 15 of
      them of the basic disease and its complications. RESULTS: The death risk was
      higher in elderly patients over 60 years of age with dyspnea duration over 10
      years and smoking history over 40 years (> 50 packs/year). In COPD death risk
      prediction factors are the following: forced expiration volume for 1 second under
      40%, SaO2 < 90%, the result of 6-min walk test < 300 m, systolic pressure in the
      pulmonary artery above 40 mmHg, right ventricular (RV) wall thickness > 0.7 cm, R
      V cavity size > 3.0 cm, relative delatation of the right atrium (index < 0.9), R
      V diastolic dysfunction, symptoms of circulatory decompensation, predisposition
      to a hyperkinetic type of circulation. When BODE index was compared to the above
      data, its reliability as a factor of death prognosis in COPD was higher.
      CONCLUSION: BODE index can be used as a simple integrative index of death risk in
      COPD.

PMID- 17526188
TI  - [Metabolic disorders in patients with chronic obstructive pulmonary disease].
AB  - AIM: To characterize cell dysregulation in chronic obstructive pulmonary disease
      (COPD) at local and systemic levels. MATERIAL AND METHODS: A total of 48 patients
      with COPD were examined (mean disease duration 11.2 +/- 7.2 years, mean age 58 +/
      4.2 years). Content of glutathione, and activity of glutathione peroxidase,
      glutathione reductase in whole blood (Novgorodtseva T.P., 2003), catalase in
      erythrocytes (Karpichenko A.I., 1999) were determined. Products of lipid
      peroxidation in exhaled breath condensate were defined to reveal diene conjugates
      of hydroperoxides, ketodienes, coupled trienes (Khyshiktuyev B.S., 1996).
      RESULTS: An evident oxidation stress at the local level was revealed in patients
      with COPD in deficiency of enzymatic antiperoxide link of anti-oxidant defense
      that is characterized by increased quantity of lipid peroxidation intermediants
      both in heptane and isopropanol phases.

PMID- 17526189
TI  - [Combined bronchodilating therapy of respiratory diseases complicated with
      bronchial obstruction].

PMID- 17526190
TI  - [Effects of systemic glucocorticoid hormones on functional indices of the
      respiratory system in patients with chronic obstructive pulmonary disease during
      acute phase].
AB  - AIM: To evaluate influence of the treatment with systemic glucocorticoid hormones
      (SGH) during acute exacerbation of moderate and severe chronic obstructive
      pulmonary disease (COPD) on parameters of respiratory function. MATERIAL AND
      METHODS: A total of 66 patients with severe COPD were included in the study.
      Airway resistance and lung volumes were measured with plethysmography, lung
      diffusion capacity - with a single breath method (TLCO SB) and saturation of
      blood with oxygen was measured with a method of pulseoximetry at admission of
      patients to a hospital and on day 14 of SGH treatment. RESULTS: Improvement of
      FEV1 by 26.3%, and a decrease in airway resistance by 44.2% (group 1) were
      observed only in 20 of 66 patients. In 46 patients improvement of airflow
      obstruction has not taken place (group 2). Dynamics of lung diffusion capacity
      and oxygen blood saturation were positive in both investigated groups of
      patients. TLCO SB has increased by 47.6% in group 1 and by 15.5% in group 2. O2
      saturation has increased by 3.2 and 3.1%, respectively. CONCLUSION: COPD symptoms
      attenuation in patients treated with SCH was associated with an increase in lung
      diffusion capacity and blood oxygen. Parameters of standard spirometry (FEV1 and
      FEV1/FVC do not reflect positive results of therapy.

PMID- 17526191
TI  - [Efficacy of a cardioselective beta1-adrenoblocker bisoprolol in patients with
      chronic obstructive pulmonary disease in combination with ischemic heart
      disease].
AB  - AIM: To study effects of a selective beta1-adrenoblocker (B1AB) bisoprolol
      fumarate (conkor, Nikomed, Germany) on severity of pulmonary hypertension (PH),
      bronchial obstruction and bioelectric activity of the myocardium in patients with
      chronic obstructive pulmonary disease (COPD) associated with ischemic heart
      disease (IHD). MATERIAL AND METHODS: Effects of an 8-week course of bisoprolol
      therapy on pulmonary hypertension, its efficacy and safety were studied in 30 IHD
      patients with COPD of stage III-IV on broncholytic therapy. The comparison group
      consisted of 45 IHD patients with COPD untreated with basic bisoprolol therapy.
      The following parameters were assessed: chest x-ray data, mean pulmonary artery
      pressure (MPAP) by echocardiography findings, frequency of anginal attacks by ECG
      monitoring, bronchial permeability by investigation of external respiration
      function, partial pressure and carbonic gas in blood, oxygen blood saturation
      (pO2, pCO2 and SaO2). RESULTS: Bisoprolol has decreased MPAP from 23.8 +/- 0.8
      mmHg to 21.9 +/- 1.0 mmHg, by 8%, p < 0.05; frequency of anginal attacks, heart
      rate from 82.2 +/- 1.4 to 73.2 +/- 1.5 b/min; number of episodes of ST segment
      depression from 2.35 +/- 0.43 to 0.95 +/- 0.22, p < 0.01; total duration of ST
      segment depression from 10.1 +/- 2.54 to 2.89 +/- 0.76 min, p < 0.01; number of
      supraventricular and ventricular extrasystoles for 24 hours from 194.5 +/- 74.4
      to 96.2 +/- 27.4 and from 239.1 +/- 124.9 to 111.3 +/- 44.1, respectively.
      Parameters of a 6 min walk test improved from 326.7 to 442 m, p < 0.01.
      Bisoprolol had no negative effect on bronchial obstruction. CONCLUSION:
      Bisoprolol is well tolerated, effective and safe in COPD patients with IHD.

PMID- 17526192
TI  - [Mechanical properties of the lungs in bronchial asthma].
AB  - AIM: To evaluate basic parameters of elastic and nonelastic resistance of the
      lungs in patients with bronchial asthma (BA) with reference to severity of
      pulmonary ventilation disorder (PVD). MATERIAL AND METHODS: PVD was diagnosed in
      92 BA patients aged 18 to 55 years (mean age 42 years, 50 males and 40 females).
      By PVD severity the patients were divided into 4 groups. The control group
      consisted of 65 healthy volunteers aged 18-54 years (mean age 45.6 years, 30
      males and 35 females). PVD degree was assessed by reduction of respiratory
      capacity (RC) and forced expiratory volume per second (FEV1), volumes of the
      lungs, ventilation speed, bronchial resistance (Raw), total respiratory
      performance, total nonelastic resistance (TNR), total nonelastic pressure,
      dynamic lung compliance, static lung compliance (Cstat), elastic lung traction
      (ELT). RESULTS: A RC fall in groups 2-4 was less significant than FEV1 reduction.
      Raw was elevated in all the groups: in group 2 the rise was more than in group 1,
      but in groups 3 and 4 the rise was similar. TNR at inhalation and exhalation
      increased from group 1 to group 3, was high in group 4. Cstat and ELT were
      similarly subnormal in all the groups. CONCLUSION: Elevation of bronchial
      resistance does not influence PVD severity. Lowering of FEV1 only partially is
      related with Raw elevation. Subnormal lung compliance may represent a
      compensatory reaction directed to overcoming valvular bronchial obstruction and
      maintenance of normal lung ventilation. Low lung traction may result from high
      mechanical activity of the lungs in condition of its estimation.

PMID- 17526193
TI  - [Heterozygosity of 198LEU mutant allele in glutathione peroxidase-1 gene as a
      risk factor of bronchial asthma associated with smoking].
AB  - AIM: To investigate whether smoking has a differential effect by Pro198Leu
      genotypes of the glutathione peroxidase-1 (GPx1) gene on the risk of bronchial
      asthma (BA) in Russian population. MATERIAL AND METHODS: DNA samples from 195
      asthmatics and 167 healthy volunteers were genotyped for Pro198Leu polymorphism
      of the GPx1 gene by polymerase chain reaction and restriction fragment length
      analysis. RESULTS: Smoking was significantly associated with an increased risk of
      non-allergic BA in males but not in females (p < 0.00001). When smoking was
      examined according to Prol98Leu polymorphism of the GPx1 gene, association of
      198Pro/Leu genotype with susceptibility to allergic BA was found only in male
      smokers (odds ratio = 2.51, 95% confidence interval = 1.04 to 6.06, p = 0.04).
      CONCLUSION: The risk of allergic BA associated with smoking is increased in males
      who are heterozygous carriers for the low-activity 198Leu allele of the
      glutathione peroxidase-1 gene. The importance of molecular mechanisms is shown by
      which functional variants of antioxidant defense genes may mediate potentially
      oxidative effects of tobacco smoke on asthmatic phenotype.

PMID- 17526194
TI  - [Clinical characteristics and condition of the bronchial tree in patients with
      bronchial asthma and chronic obstructive pulmonary disease in combination with
      hyperoxaluria].
AB  - AIM: To evaluate peculiarities of a clinical course and changes in bronchial
      mucosa in bronchial asthma (BA) patients with chronic obstructive pulmonary
      disease (COPD) in combination with hyperoxaluria (HOU); informative value of some
      laboratory and device findings including oxalates assay in bronchial lavage fluid
      for specification of the diagnosis, role of oxalates in development of
      obstructive syndrome and choice of optimal therapy. MATERIAL AND METHODS:
      Oxalates were examined in daily urine, bronchoalveolar lavage fluid and exhaled
      air condensate of 104 patients with BA and COPD, 77 of which had HOU and an
      atypical course of bronchial obstruction syndrome. RESULTS: Conception of airways
      inflammation in patients with oxalate metabolism disturbances is proposed. It is
      shown that insoluble oxalates participate in pathogenesis of bronchial
      obstruction. CONCLUSION: Oxalate metabolism disturbances are an important factor
      in pathogenesis of airways inflammation and development of bronchial obstruction
      in predisposed patients. Therefore, administration of insoluble oxalates lowering
      therapy may effectively prevent formation and progression of obstructive
      pulmonary diseases in this group of patients.

PMID- 17526195
TI  - [Effects of combined therapy with domestic inhalational anti-asthmatic drugs on
      oxidant status of patients with bronchial asthma].
AB  - AIM: To compare effectiveness of two combinations of domestic drugs in the form
      of dry powder for inhalation-biasten containing budesonide plus salbutamol
      hemisuccinate and benacort (budesonide) plus salben (salbutamol) in correction of
      disorders of the blood oxidant-antioxidant system (OAS) in patients with moderate
      bronchial asthma (BA). MATERIAL AND METHODS: A total of 46 patients with
      uncontrollable BA of moderate severity (16 males and 30 females) entered an open
      trial where they were randomized into two groups. Group 1 (n=25) inhaled biasten
      (2 inhalations 2 times a day), group 2 (n=21) received equivalent doses of
      benacort and salben for 12 weeks. The following parameters were assessed: a
      clinical response, peakflowmetry, flow-volume curve, daily need in beta2
      agonists, OAS by intensity of methemoglobin (MET) spectra, free radicals (FR),
      catalase, ceruloplasmin, transferrin, superoxidedismutase (SOD). RESULTS: Biasten
      treatment for 12 weeks brought about a good control over BA symptoms in 72%
      patients, satisfactory--in 24%, no control--in one patient. In combined therapy
      with benacort and salben the respective percentage was 71.4 and 19.1, failure--in
      2 patients. A clinical response in both groups differed insignificantly. The
      responders showed significant correction of OAS unbalance (but not of OAS
      erythrocytes), reduction of MET and FR concentrations, elevation of SOD and
      catalase. Anti-oxidant properties of blood plasm did not change significantly in
      response to the studied drugs administration. CONCLUSION: Both biasten and
      benacort in combination with salben provide BA control, reduce severity of free
      radical oxidation disorders.

PMID- 17526196
TI  - [Intravascular laser irradiation of blood in the treatment of patients with
      bronchial asthma].
AB  - AIM: To investigate action of intravascular laser blood irradiation (ILBI) on
      production of active oxygen forms (AOF) in patients with bronchial asthma (BA).
      MATERIAL AND METHODS: The trial included 59 BA patients aged 20 to 60 years (mean
      age 40.2 +/- 3.1 years). AOF generation in whole blood was registered with
      luminol-dependent chemiluminescence (CL). Basic therapy was given to 42 patients.
      ILBI was added to basic therapy in 17 patients. RESULT: . CL of whole blood in BA
      patients depended on severity of inflammation. BA patients with intensive CL
      exposed to ILBI retained free radical oxidation defects and the disease symptoms.
      In low intensity of blood CL, ILBI activated A OF generation and raised treatment
      effectiveness. CONCLUSION: ILBI raises AOF production in the whole blood of BA
      patients. CL registration can be used for validation of ILBI administration in BA
      patients and control of effectiveness of laser therapy.

PMID- 17526197
TI  - [Bronchial capacity in community-acquired pneumonia].
AB  - AIM: To examine bronchial capacity (BC) in patients with community pneumonia (CP)
      by speed characteristics of pulmonary ventilation function (PVF) and bronchial
      resistance (Raw). MATERIAL AND METHODS: Monitoring of a peak expiration speed
      (PES) was made in 99 CP patients. In addition, 46 of them have undergone
      spirometry and bodyplethysmography (Masterlab pro device) with measurement of
      airflow speed, Raw and structure of total lung capacity. RESULTS: In 88.9%
      patients with CP the initial PES was subnormal but its normalization occurred (in
      79.7%) within 3 days of stable normalization of body temperature. This was
      confirmed by a strong negative correlation between the initial PES and body
      temperature in admission of CP patients to hospital (r = -0.73, p = 0.001). Raw
      in 86.9% patients with CP is normal (74.53 +/- 4.50%) both in moderate and acute
      fall of PVF speed characteristics. If these characteristics in CP patients are
      low, Raw should be examined. High Raw in this case justifies the diagnosis of
      latent chronic obstructive pulmonary disease. CONCLUSION: Raw in 86.9% CP
      patients is normal, thus indicating no impairment of bronchial capacity.
      Obstructive disorder of lung ventilation in acute CP detected at spirometry is
      explained by non-pulmonary causes. For diagnosis of BC affection in patients with
      CP and low speed characteristics of PVF, bronchial resistance must be examined.
      High bronchial resistance in such cases indicates latent chronic obstructive
      pulmonary disease.

PMID- 17526198
TI  - [Osteogenon in therapy of distal radial bone fractures in patients with secondary
      osteoporosis].
AB  - AIM: To assess efficacy of osteogenon in consolidation of solitary fractures of
      distal part of the radial bone (RB) in patients with secondary osteoporosis (SO)
      due to rheumatoid arthritis (RA) and chronic renal failure (CRF). MATERIAL AND
      METHODS: The study group consisted of 7 patients with documented RA and 8
      patients with CRF caused by chronic glomerulonephritis or chronic pyelonephritis
      in the predialysis period. The control group comprised 13 patients (6 and 7
      patients, respectively). The patients were matched by clinico-demographic and
      therapy characteristics. Patients of the study group received osteogen from the
      fracture diagnosis to its consolidation. RESULTS: Osteogenon has an analgetic
      effect, improves well being, raises physical activity, reduces duration of
      fracture consolidation in patients with SO.

PMID- 17526199
TI  - [Individual application of a personal computer in practice of the pulmonologist:
      the experience with 12-year monitoring].

PMID- 17526200
TI  - [Non-esophageal manifestations of gastroesophageal reflux disease].

PMID- 17526201
TI  - [Severe acute respiratory syndrome].

PMID- 17526202
TI  - [Pulmonary histiocytosis X].

PMID- 17526203
TI  - [Endothelial dysfunction and respiratory diseases].

PMID- 17526204
TI  - [Systemic vasculitis and atherosclerosis].

PMID- 17526205
TI  - [Beta-adrenoblockers in chronic stable ischemic heart disease].

PMID- 17526206
TI  - [To the mechanism of enhancing the activity of serum and hepatic sorbitol
      dehydrogenase in rats fed excess sweetener sorbitol].
AB  - One-month rats were randomized to a diet containing sorbitol (SOR) (54%),
      saccharose (SACCH) (54%) or that containing SOR (27%) and SACCH (27%). They were
      kept on the diets for 1 or 3 months. At the age of 2 and 4 months, the rats were
      returned to the routine diet of a vivarium. The experiments were terminated when
      the rats were aged 2, 4, and 7 months. In all seasons, the monthly diets
      containing 27% and 54% of SOR increased the serum activity of sortibol
      dehydrogenase (SDH) by several and tens of times. The 3-month diet produced the
      same effect. It suddenly turned out that the 54% SACCH diet also increased SDH
      activity, but to a lesser extent than a combination of 27 SOR and 27% SACCH, and
      by tens of times less than the 54% SOR diet. Comparison of three diets showed the
      same relationship between the increases in SDH activity in the liver. With excess
      dietary SOR, a very high increase was first found in serum and hepatic SOD
      activity by an induction mechanism.

PMID- 17526207
TI  - [Effect of sapropel mud on the parameters of oxidative stress and antioxidative
      defense in acute carbofos poisoning].
AB  - Sapropel was tested for its effect on the permeability of erythrocytic membranes
      and on the erythrocytic and serum levels of ceruloplasmin, malonic dialdehyde,
      and dienic conjugates in rats after acute poisoning by carbofos, a malathion
      insecticide. The increased processes of free radical oxidation during carbofos
      poisoning were suggested by the higher rates of chemiluminescence of erythrocytes
      and peripheral blood serum. No significant changes in the parameters of blood
      oxidative stress in the carbofos-poisoned animals during therapeutic-and
      prophylactic use of sapropel indicate that the latter has antioxidative
      properties. Application of sapropel to normal animals exerted no effect of the
      studied parameters of oxidative stress. In acute carbofos poisoining, oral
      sapropel produced a pronounced antioxidative effect, which opens up new vistas
      for its practical application.

PMID- 17526208
TI  - [Use of mesenchymal stromal cells applied to composite materials to optimize bone
      tissue regeneration].

PMID- 17526209
TI  - [Age-related changes in the exchange of hexosamine-containing biopolymers in rats
      under immobilization stress].
AB  - Daily double spinal immobilizations (for 60 minutes, at intervals of 7-8 hours)
      for 3 days were studied for their impact on the metabolism of hexosamine
      containing biopolymers in the mucosa of the stomach and lung in male rats of
      different ages (kids, adults, and olds). At the same time, the highest increases
      in the level of hexosamine glycane, glycoprotein, and hexosamine-containing
      glycopeptides and a rise in the activity of the lysosomal enzymes N-acetyl-beta-D
      hexosaminidase (EC 3.2.1.52) and alpha-L-fucosidase (EC 3.2.1.51) were revealed
      in the gastric mucosal homogenates in the growing rats.

PMID- 17526210
TI  - [Intestinal endotoxin in the pathogenesis of ocular inflammatory diseases and the
      antiendoxin constituent of its treatment].
AB  - Blood was studied in 119 patients with ocular inflammatory lesions:
      endophthalmitis (n = 10), iridocyclitis of viral (n = 47) and unknown (n = 62)
      genesis, by using the procedures developed by the authors to determine the
      integral values of the concentration of endotoxin in systemic blood flow and the
      activity of antiendotoxin immunity. Intestinal endotoxin aggression was found to
      be involved in the pathogenesis of ocular inflammatory diseases. The use of drugs
      and procedures, which could diminish the entry of intestinal endotoxin into the
      blood stream and intensify the processes of its binding and release from systemic
      blood circulation, substantially enhanced the efficiency of a therapeutic
      process.

PMID- 17526211
TI  - [The complex adaptogenic drug tonizid attenuates myocardial contractile
      dysfunction and prevents irreversible cardiomyocytic damages in ischemia and
      reperfusion of the isolated heart].
AB  - A course administration of the complex plant adaptogenic drug tonizid was
      ascertained to increase murine exercise tolerance. In addition, the drug
      increased murine survival during hypobaric hypoxia (at an altitude of 10,500 m
      upon 20-min exposure). A model of total 35-min ischemia and that of 30-min
      reperfusion of the rat isolated heart were used by the Langendorff technique. The
      course administration of tonizid attenuated a reperfusion decrease in the left
      ventricular pressure and in the rate of contraction. However, tonizid did not
      prevent a reperfusion reduction in heart rate, a decrease in the rate of
      relaxation and an elevation of end diastolic pressure. Tonizid lowered the level
      of creatine kinase in the venous effluent from the isolated rat heart during
      reperfusion. At the same time, the plant adaptogen exerted no effect on the
      incidence of ventricular arrhythmias and coronary flow. It has been suggested
      that tonizid is an adaptogenic drug that attenuates contractile dysfunction and
      prevents irreversible cardiomyocytic damage during ischemia and reperfusion of
      the isolated heart.

PMID- 17526212
TI  - [Role of lysosomal enzymes in the genesis of major clinical and
      pathophysiological syndromes: facts and hypotheses].

PMID- 17526213
TI  - [The immunophysiological and immunopathological aspects of scleroderma
      systematica: fundamental and clinical aspects].

PMID- 17526214
TI  - [Use of the immunomodulator polyoxidonium in combination with non-collagen bone
      proteins to accelerate jaw regeneration in experimental immunodeficiency].

PMID- 17526215
TI  - [The situation and preventive measures against the spread of avian influenza on
      the territory of the country].
AB  - The Russian Federation, as the whole world community, is anxious about the
      established situation associated with the prevalence of avian influenza and a
      threat of its pandemic. Today avian influenza is a complex, i.e. medical,
      veterinary, social, and economic, problem. Since December 2003, the world has
      notified an avian influenza panepizootic that has covered 54 countries to date.
      Despite emergency measures to prevent the prevalence of this infection, resulting
      in the elimination of more than 100 million poultries, the virus has fixed in the
      natural population of wild birds and gained the capacity to infect human beings,
      which serves as a guide for considering it a possible predictor of pandemic
      virus. According to the WHO classification, the Russian Federation is at Step II
      of an interpandemic period when cases of the disease are not notified among the
      population; however, the subtype circulating among the animals can cause the
      disease to sufficient probability. To prevent mass mortality of influenza virus
      infected birds and human contagion in the inhabited localities wherein epizootic
      is seen, the Russian Federation has organized and implemented a package of
      antiepizootic, veterinary-sanitary, and sanitary-antiepidemic measures, including
      on-line exchange of information on the epizootic and epidemiological situation
      with veterinary surveillance bodies; farmstead rounds are made for the early
      detection of ill persons among human beings, for which an additional medical
      personnel has been picked out; daily medical monitoring of the population and the
      workers of poultry factories, wherein poultry death has been recorded, has been
      organized; the places of annihilation of utilized fallen and forcedly killed
      poultry are notified; supervision of the sanitary and veterinary state of the
      market where alive poultry and ornamental birds are sold has been tightened;
      measures to lay in a stock of chemotherapeutical and chemoprophylactic agents
      producing an antiinfluenza effect, as well as that of disinfectants have been
      taken; poultry and other birds are daily examined. Three inactivated emulsified
      veterinary vaccines against avian influenza have been currently designed. The
      calculated size of poultry to be vaccinated is 74.6 million. Double vaccination
      requires that 150 million doses of the agent be manufactured.

PMID- 17526216
TI  - [Influence of environmental and climatic factors on the incidence and course of
      stenosing laryngotracheitis in children with acute respiratory diseases].
AB  - A clear correlation was found between the development of stenosing
      laryngotracheitis (SLT) in the presence of viral infection, its severity, and the
      environment well-being of an area where a child resides. The level of
      environmental pollution and the interaction of environmental factors and weather
      climatic ill-being, which vary with time and have regional features, adversely
      affect the course of SLT and require mandatory correction during complex therapy
      and seasonal antirecurrent treatment. The increase in the incidence of childhood
      SLT may be a biological indicator of the environmental ill-being of a region.

PMID- 17526217
TI  - [Impact of ambient air pollution on allergic morbidity in children in a large
      industrial town].

PMID- 17526218
TI  - [Evaluation of Bishkek air pollution with polyaromatic hydrocarbons].
AB  - The purpose of this study was to make a quantitative assessment and prediction of
      the degree of ambient air benzo(a)pyrene pollution in Bishkek and to develop
      environmental PAH reduction measures. Analysis of the data shows that the
      greatest ambient air benzo(a)pyrene pollution was observed in the central and
      northern parts of the town (up to 46 maximum allowable concentrations - MAC), the
      bedroom communities situated in the southern part of the town can be described as
      conditionally clean (up to 10.3 MAC). The main sources of pollution are motor
      transport and energy-fuel enterprises. Prediction analysis indicates a linear
      increase in annual rates. BaP accumulation and decomposition was also found to be
      periodic and, if appropriate measures are not undertaken, BaP concentrations
      might increase up to 80 MAC in a short time.

PMID- 17526219
TI  - [Medical waste: the problem of handling].
AB  - The paper provides the environmental and hygienic characteristics of medical
      waste, the necessity of introducing a new system of collection, storage,
      transportation, and removal of waste from health care facilities. In accordance
      with SanPiN 2.1.7.728-99 (subparagraph 8.7.9.3a), an enterprise for thermal
      decontamination of hazardous waste should be necessarily set up with the purpose
      of possible removal of classes B and C garbage to the polygons, which will secure
      medical waste to man and the environment.

PMID- 17526220
TI  - [Use of air ultraviolet irradiation in the Moscow Metro].

PMID- 17526221
TI  - [Agricultural aspects of aquatic environmental toxicology (a review of
      literature)].
AB  - The impact of agriculture on water ecosystems is considered. The negative effects
      of entry of pesticides and biogens into the aquatic environment, which lead to
      its pollution and eutrophication and biota change and degradation, are shown. The
      author discusses whether it is necessary to meticulously monitor the aquatic
      environment in the intensively agricultural areas.

PMID- 17526222
TI  - [Problems in the handling with environmentally hazardous benz(a)pyrene-polluted
      soils during construction on the territory of Moscow].

PMID- 17526223
TI  - [Negative impact of video display terminals on the organs of vision].
AB  - The negative impact of video display terminals (VDT) on the visual system was
      examined in personal computer users. The most significant unfavorable aspects of
      VDT users' work, such as visual work intensity, the improper illumination of
      working places, the low quality of used computer machinery, as well as general
      nonobservance of the established standards are indicated. The paper shows it
      necessary to pay particular attention to the problem associated with the work of
      users with myopic refraction, with the strict hygienic regulations of VDT work,
      and with the use of preventive measures to prevent abnormalities of the organs of
      vision.

PMID- 17526224
TI  - [The functional status of the thyroid in patients with psychoneurological
      consequences of acute poisoning with high-toxic organic phosphorus compounds].
AB  - The paper presents the data of a clinical study of the functional status of the
      thyroid in patients who experienced acute sarin and soman intoxication that was a
      cause of various psychoneurological disorders. The reduced blood level of thyroid
      hormones in the examinees and the absence of its normalization suggest severe
      thyroid dysfunction, which allows necessary therapeutic measures to be warranted.

PMID- 17526225
TI  - [Hygienic assessment of working conditions and functional resistance in electric
      power station workers].
AB  - The exceeding maximum permissible levels, the parameters of electromagnetic
      fields and radiations, an electrostatic field, noise, and vibration are the
      leading adverse factors of the industrial environment for basic professional
      groups of Stavropol district electric power station workers. According to the
      degree of harmfulness and hazard, the working conditions are referred to as Class
      3 ("hazardous") in 93.7% of the personnel. The significant tension of adaptive
      mechanisms is typical of most patients (76.3%). Based on the multivariate
      analysis of the results of a psychophysiological follow-up, the authors have
      developed a procedure for the integral evaluation of the functional state of the
      workers' organism, which may be used in the sociohygienic monitoring system in
      the electric power system of Russia.

PMID- 17526226
TI  - [Hygienic assessment of the intake of fish products and their quality].
AB  - The impact of provision of the population with fish products and the level of
      their intake on public health was studied. Analysis of statistical data and the
      results of the authors' own data has provided strong evidence that the reduction
      in the volume of catch of water biological resources, the production, and intake
      of their foodstuffs, as well as the low actual quality of fish products on the
      consumer market significantly deteriorate the indices of the population's health
      state.

PMID- 17526227
TI  - [The major sources of daily dietary intake of micronutrients in the adult rural
      population of the Republic of Chuvashia].
AB  - The paper presents the results of determination of the basic sources of
      micronutrients in the nutrition of the rural population of the Chuvash Republic.
      The importance of foodstuffs, the sources of nutrients, was determined by factor
      mathematical analysis, by estimating the weight factors. All the products used in
      the daily ration were studied, which permitted elucidation of the importance of
      individual Russia-specific products. By reason of the uniform pattern of
      nutrition in Chuvashia, virtually all study micronutrients were found to come
      with baked goods, milk, and potatoes. The quantity of fresh vegetables and fruits
      in the actual diets of the examinees is so low that it exerts no significant
      effect on the intake of vitamins and minerals. In addition, all vegetables and
      fruits used in the daily ration are generally used in the personal subsidiary
      plots. Berries that commonly grow in Chuvashia, such as cranberry, bilberry, sea
      buckthorn, and red whortleberry, were also observed to be virtually unused in
      nutrition, although it is just the berries that are gold mines of vitamins and
      minerals.

PMID- 17526228
TI  - [The physical development and health status of senior preschool children from
      compensating orthopedic groups].

PMID- 17526229
TI  - [Comparative characteristics of the physical development of adolescents of the
      Republic of Tuva and other ethnic groups].

PMID- 17526230
TI  - [Age-related changes in the physical development of Kabardin-Balkarian school
      children living at various heights above sea level].
AB  - Four and eighty-one schoolchildren aged 7-17 years, living at a height of 2100 m
      above sea level, and 1677 schoolchildren of the same age, living at a height of
      100-400 m above sea level, from the Kabardin-Balkarian Republic were examined by
      the list of morphological indices of physical development (PD), such as height
      (cm), body weight (kg), and chest circumference (cm). The results were rated by
      using the 5-score scale, by calculating the integral indicator of PD (low,
      moderate, and high). The schoolchildren living at high heights were ascertained
      to have high values. In the schoolchildren living at low heights, PD is of more
      harmony; the altitude children have the developed chest along with the smaller
      height and lower body weight. The geographical differences in three parameters of
      PH between Kabardin-Balkarian schoolchildren were heterodirectional: the altitude
      children outrun the plain one in height during a short period of time (the boys
      outrun at the age of 10 to 13 years; the girls do at the age of 11 to 14 years).
      In terms of body weight, the children from the study groups either outrun, or lag
      each other, in the boys and girls, these variations being opposite in time. From
      the age of 10 years, the altitude children of both sexes surpass the plain ones
      in chest circumference.

PMID- 17526231
TI  - [Development and scientific rationale for a universal index for rapid assessment
      of readability].
AB  - The hygienic regulations of academic books, including teachware, for children and
      adolescents necessitate the performance of special studies to assess their
      readability by the unified procedure that would suggest a visual response while
      reading. This study has developed and warranted a universal readability index by
      the velocity of reading. There are significant regression correlations between
      the velocity of reading as the readability index and the degree of tiredness,
      detected by various visual functions. The parameters of accommodation and
      adaptive properties of the eye are most sensitive to visual load on reading.
      Reading velocity as an indicator of readability of illogical texts may be used as
      a rapid method under laboratory and natural conditions to determine the action of
      various textual loads on the visual system.

PMID- 17526232
TI  - [Assessment of the adaptation of junior students to academic activity].
AB  - The adaptation of junior students to academic activity was studied on the basis
      of changes in hemodynamics, automatic cardiac rhythm regulation, and a simple
      visual monitoring response (SVMR) during an academic year in the relation of
      their progress in studies. A number of the parameters of SVMR, hemodynamics, and
      cardiac rhythm variability were revealed, which significantly differ in the
      examinees who had low results and who had high results.

PMID- 17526233
TI  - [Students' life quality: current problems].
AB  - To study the quality of students' life has been a challenge today. The paper
      contains the data of a study of life quality in male students who will be
      physical education teachers. Health is an indicator of the quality of the
      population's life. The study established deterioration of the students' health
      during their studies caused by the improper organization of a teaching-and
      educational process. Therefore, this deteriorates the quality of the students'
      life. The findings show it necessary to further work-up this problem and to
      reveal the most significant factors of students' life quality.

PMID- 17526234
TI  - [Study of allergic morbidity in children of female workers from various fields of
      national economy].
AB  - To study the factors contributing to the development of allergic disease in
      children has recently become of current importance. To determine the indirect
      influence of maternal working environmental factors on allergic morbidity in
      children, the authors have examined the working conditions and morbidity of
      female workers engaged in that or that field of national economy and the health
      status and allergic diseases in children. The variance analysis was made. The
      proposed guidelines allow one to study the indirect influence of working
      environmental factors on allergic morbidity in children.

PMID- 17526235
TI  - [Cardiac rhythm in pupils during tests].
AB  - Variation pulsometry was used to study changes in the activity of cardiac rhythm
      regulating mechanisms in third-form pupils from a comprehensive school (a control
      group) and a gymnasium (a study group) under mental stress caused by the
      performance of mathematical tests. Two types of responses of the studied
      parameters: sympathetic (in the study group) and parasympathetic (in the control
      group), which were determined by the richness and intensity of an academic load
      and by the readiness of both categories of school-children, were identified.

PMID- 17526236
TI  - [Impact of prolonged nitrite intoxication on the erythrocytic system of pregnant
      rats and their progeny].
AB  - Pregnant rats with nitrite intoxication have less erythropenia than those without
      this intoxication. Under the influence of sodium nitrite, fetuses have stimulated
      erythropoiesis. These changes preserve in one-day rats. By the 21st day of life,
      there is erythropenia due to the exhaustion of erythropoietic reserves.

PMID- 17526237
TI  - [Some psychological characteristics of persons exposed to small-dose methylated
      mercury].
AB  - In the area polluted by the man-caused mercury in the Angara River reservoir,
      there is fish accumulation of the toxic substance in the quantities exceeding the
      standard values by 2-4 times. The psychological characteristics of the persons
      exposed to mercury load due to fish ingestion were studied. A screening survey
      revealed the high situational and personality anxiety in 33.9 +/- 6.2 and 53.9 +/
      6.2% of the examinees, respectively. Lower logical and abstract thinking
      abilities were observed in 92.7 +/- 2.8% of the respondents. Poorer attention,
      significant fatiguability, and distraction were seen. According to the level of
      mercury in the biosubstrates, a risk group (n = 26) was formed, which was
      examined in the inpatient setting. The high prevalence of emotional instability
      and neurotism was revealed. When examined by a psychiatrist, 9 persons were
      recognized as apparently healthy. It is necessary to continue studies to
      objectivize the conclusion that small-dose methylmercury affects mental health.

PMID- 17526238
TI  - [Evaluation of the hazard of soil-polluting chemicals upon exposure of
      experimental animals].
AB  - The experimental study of the biological activity of the modified calcium
      chloride produced by a Volgograd plant and that of ash-and-slag of the
      pharmaceuticals resulting after combustion of a pyrolytic mixture of filtration
      burning could establish various hazards of these substances.

PMID- 17526239
TI  - [Hygienic evaluation of hydrolytic lignin waste, by using alternative test
      models].
AB  - Chemical analysis showed that lignin samples contained phenols, phenanthrene, and
      methanol. The highest total content of organic compounds was noted in the lignin
      samples taken directly at a manufacturing plant. Phenols prevailed in the upper
      layers of stored lignin samples and methanol predominated in the lower ones.
      Studies on Tetrahymena pyriformis infusoria indicated that the fresh lignin
      samples are most toxic. A number of the samples exerted pronounced cytotoxic and
      genotoxic effects when the mollusks Limneae stagnalis and murine embryonic
      fibroblasts were examined.

PMID- 17526240
TI  - [Field trials of the impact of chemical air pollution on rabbit formed blood
      elements].
AB  - Ufa is the capital of the Republic of Bashkortostan is a large center of chemical
      and petrochemical industry. Pollution of the environment spreads to the vicinity
      of the city. Under these conditions, of great importance is a combination of
      influences of low-intensity chemical factors on living organisms in the
      settlements rather than an influence of individual chemical reagents. It is most
      adequate to explore the latter through field trials, i.e. to monitor the status
      of experimental animals during their stay in the area under study. The blood
      system is the most informative indicator, therefore peripheral blood formed
      elements were used as test objects. The authors have established the following:
      1. No significant changes were found in the peripheral blood formed elements of
      adult rabbits in the control group during their 3-month stay in the settlement of
      Gornyi, Chishminsky District (Republic of Bashkortostan). 2. The 3-month
      monitoring of experimental rabbits revealed some changes in their peripheral
      blood formed elements, which pointed to a certain level of hemic hypoxia. 3. The
      magnitude of the found blood changes in the experimental animals of Group 1 from
      the settlement of Tsekh Kerami (Ceramics Shop), Blagoveshchensky District, was
      higher than that in Group 2 from the village of Kabakovo, Karmaskalinsky District
      (Republic of Bashkortostan).

PMID- 17526241
TI  - [The hygiene and toxicology of fertilizers at the present stage].
AB  - The paper touches upon the topical aspects of the hygiene and toxicology of
      fertilizers and their state sanitary-and-epidemiological examination at the
      present stage. It also considers guidelines for the toxicological-and-hygienic
      evaluation when state trials are carried out.

PMID- 17526242
TI  - [Impact of modification of the fiber surface of chrysotile on its biological
      activity].
AB  - Samples of commercial chrysotile-asbestos and asbestos cement, which were equal
      in number, were prepared. The content of fibers, up to 80 microm in length, was
      87.4 and 85.0% in the first and second samples, respectively. Chemical analysis
      confirmed that there were cement components onto the surface of fibrils in the
      second sample. Onto the surface of native asbestos fibers, there were
      considerable distribution bands of active centers in the range of pH values of 5,
      6.4, and 7.3; their largest number was at pH 6.4. Asbestos cement fibers had a
      band at pH 7.3, i.e. there was displacement towards the neutral region. Thus,
      their capacity for oxidative processes is likely to be lower than that in the
      fibers from the first sample. The mutagenic activity of the commercial
      chrysotile, examined in the micronucleus test, was substantially higher (p <
      0.01) than that in the asbestos cement sample wherein it did not differ from that
      seen in the control experiment (saline solution). Mutagenicity was not found in
      cement and asbestos cement dust (2-3% of fibers) either. It is probable that the
      absence of mutagenicity in the cement-coated asbestos fibers may be attributable
      to a considerable reduction in their potencies for the formation of active
      radicals (oxygen, lipid peroxidation, and others).

PMID- 17526243
TI  - [Method for comprehensive assessment of the parameters of psychophysiological
      adaptation in junior Lyceum pupils].

PMID- 17526244
TI  - [Optimization of preparation of samples for the sanitary-and-epidemiological
      examination of toys].

PMID- 17526245
TI  - [The social and health status in the handicapped living in Varna (Bulgaria)].

PMID- 17526246
TI  - [First experience with a Gamma-knife unit used for radiosurgical treatment for
      intracranial space-occupying lesions].
AB  - A Gamma-Knife unit that is currently the gold standard in radiosurgery was first
      used in clinical practice in 1968. The essence of the radiosurgical treatment is
      to apply the stereotactic technique to high-precision irradiation of small
      intracranial targets by narrow beams of ionizing radiation from external sources.
      Three hundred and six patients with various intracranial diseases (137 with
      malignant tumors, 136 with benign tumors, and 33 patients with vascular diseases)
      underwent radiosurgery on a Gamma-Knife unit for over 1.5 years, from May 2005 to
      October 2006. A total of 329 irradiation sessions were performed. By summing up
      the first results, it can be noted that stereotactic radiosurgery using a Gamma
      Knife unit is an effective and rather safe technique in the treatment of patients
      with various types of intracranial pathology, which maintains the high quality of
      life, reduces the likelihood of development of different neurological disorders
      after treatment and avoids the risk of operative complications. The possibility
      of performing outpatient treatment for a diversity of diseases without mandatory
      anesthesiological, ICU, and rehabilitative maintenance, determines the potential
      economic efficiency of this treatment.

PMID- 17526247
TI  - [Choice of trephining in surgery for severe brain injury].

PMID- 17526248
TI  - [Stepwise surgical treatment in patients with multiple stenotic and occlusive
      lesions of the great arteries of the brain].
AB  - The study was conducted at the Academician N. N. Burdenko Institute of
      Neurosurgery, Moscow, in 1999 to 2006. The paper presents the results of stepwise
      surgical treatment in 84 patients with chronic cerebral ischemia, caused by
      multiple stenotic and occlusive lesions of the brachiocephalic arteries, who
      underwent 183 reparative operations. Six major groups of patients with various
      combinations of lesions of major cerebral arteries were identified. An attempt
      was made to create an algorithm of the optimum stepwise surgical treatment policy
      in the identified groups of patients on the basis of the site, degree, and nature
      of stenotic lesions, by taking into account the cerebral hemodynamics and
      collateral circulation at all stages of surgical treatment. At the same time,
      changes in the degree of neurological deficit as one of the major determinants of
      the results of surgical treatment could be evaluated. The study has demonstrated
      that the chosen tactics of employing series arterial reconstructions in multiple
      stenotic and occlusive lesions of major cerebral arteries is an effective
      treatment option in patients with chronic cerebral ischemia.

PMID- 17526249
TI  - [Arterial wide-section anastomoses: experimental study on animals].
AB  - A mechanical device for making arterial wide-section anastomoses was tested on a
      series of 15 laboratory rabbits. End-to-side anastomoses were made using a vein
      graft and they functioned in 93.1% of cases, as evidenced by intraoperative
      Doppler studies. When an anastomosis is made, the mean duration of temporary
      blood flow arrest in the rabbit aorta averaged 2 min. According to outcomes, the
      survived animals were divided into 3 groups: Group 1 comprised 2 (13.3%) rabbits
      that died within 10-12 hours after surgery and had significant symptoms of
      anastomotic dysfunction. Group 2 included 8 (53.3%) animals that died 2-3 days
      after surgery. They moved 5-6 hours following surgery without assistance, which
      was indicating of anastomotic functioning. Group 3 consisted of 3 (20%) rabbits
      that survived 2 weeks. Autoptic studies revealed no anastomic thrombosis in Group
      2 animals. Group 3 animals were noted to have signs of allograft thrombosis and
      rejection. Thus, it is expedient to continue studies to make arterial wide
      section anastomoses, by using the above device, in order to introduce this
      procedure into clinical practice.

PMID- 17526250
TI  - [25 years' experience in surgically treatment of the epilepsy].
AB  - Progress in surgical treatment for unifocal epilepsy is evident. The efficiency
      of surgical treatment for multifocal epilepsy in cases when pathology of the
      brain is not seen on MRI remains to be inadequate and by large and large the
      problem is to be solved. MATERIALS AND METHODS: In 1978 to 2004, the epilepsy
      center of the Republic of Moldova performed 258 operations in 215 patients with
      drug-resistant epilepsy. These included 28 temporal lobectomies, 46 cortical
      resections, 151 stereotactic operations, 6 resection-and-stereotactic operations,
      and 27 implantations of diagnostic intracerebral electrodes (SICE). The
      operations were performed in a specialized operating suite. The authors developed
      stereotactic apparatuses, intracranial electrodes, and chemoelectrodes.
      Intraoperative diagnosis included video monitoring, echography, stereotactic
      electroencephalography (SEEG), electric studies, drug induction of a seizure,
      cortical anatomic and functional mapping, and determination of resection
      boundaries. Stereotactic destructions were made by diathermo- and cryotechniques.
      RESULTS: In temporal epilepsy, stereotactic hippocampotomy yielded good,
      satisfactory, and poor results in 23, 44, and 33% of cases, respectively.
      Amygdalohippocampotomy did these results in 33, 39, and 28%, respectively.
      Excellent and good results of open operations amounted to 42%. These of anterior
      temporal lobectomy were observed in 69%. CONCLUSIONS: 1. Stereotactic
      hippocampotomy is most effective in unifocal temporal epilepsy. Bilateral
      amygdalohippocampotomy has a marked psychosedative effect. 2. In 65%, the site of
      an epileptic focus failed to enable its resection to be radically made. 3.
      Temporal lobectomy is most beneficial in temporal epilepsy. 4. Intraoperative
      Talairach's SEEG, followed by resection is most effective in nontemporal
      epilepsy. 5. SICEs enhance the efficiency of resections by 2 times, stereotactic
      operations by 15%, without affecting the results of temporal lobectomy.

PMID- 17526251
TI  - [Venous thromboembolic events in neurosurgical patients. Part I. Analysis of
      their incidence on the basis of autopsy material].

PMID- 17526252
TI  - [The topographic anatomy of the interpeduncular cistern and endoscopic
      ventriculocisternostomy in the region of the bottom of the third ventricle].
AB  - The interpeduncular cistern was microanatomically studied on 14 anatomic
      specimens of the brain. It was divided into 2 parts: superficial (free) and deep
      (vascular). The upper interpeduncular cistern wall was divided into hypothalamic
      and mesencephalic parts. The interpeduncular cistern is connected with the
      ambient, pretontine, carotid, cerebellopontine, oculomotor, and peduncular
      cisterns. It is a composite space-occupying, structural formation. Liliequist's
      membrane is the basic membranous component of a cistern. The proposed division
      makes it possible to study different parts of the interpeduncular cistern
      qualitatively and quantitatively and to define clear topographic and anatomic
      criteria as a guideline in this field.

PMID- 17526253
TI  - [The leptomeningeal form of primary neuroectodermal tumor].
AB  - Brain neoplasms as primary leptomeningeal forms are rare, particularly if the
      case in point is primary neuroectodermal tumors (PNET). In the literature, there
      are only few reports on this topic. The authors describe one of such rare cases.
      A 21-years-old man was admitted to a hospital for complaints about headache.
      Brain computed tomography and magnetic resonance imaging (MRI) revealed internal
      hydrocephalus and slightly uniform meningeal thickening without the signs of
      space-occupying lesions. Ten months after ventriculoperitoneostomy, the patient
      suddenly developed tetraparesis and respiratory disorders. MRI showed a
      pronounced diffuse non-uniform leptomeningeal dissemination of a tumor. Open
      biopsy of the lesion in the projection of the right fissure detected PNET. The
      patient underwent a course of chemotherapy (CCNU, vincristine) and radiotherapy
      (total focal dose 45 Gy). Control MRI could not identify a pathological
      leptomeningeal signal.

PMID- 17526254
TI  - [History of surgery for parasagittal meningiomas].

PMID- 17526255
TI  - [Neurostimulation in patients with chronic neuropathic pain in the so-called
      failed back surgery syndrome (world and the author's experience)].
AB  - The failed back surgery syndrome (FBSS) is defined as protracted or recurrent
      pain, mainly in the lower back and/or legs, even after previous anatomically
      successful spinal surgery. Treatment of such patients commonly involves
      difficulties since neither medical therapy nor repeated back surgery does not
      result in adequate pain relief. Spinal cord stimulation (SCS) is a minimally
      invasive procedure that allows physicians and patients to define the effect of
      therapy just before permanent implantation. Both trial stimulation and permanent
      implantation are fully reversible. Early treatment with SCS has been shown to be
      very effective in correctly selected FBSS patients and therefore this procedure
      should be preferred over back resurgery. Clinical studies have demonstrated that
      CSC provides a sustained, long-term, 50% or more pain relief in over 60% of the
      patients and makes it possible to reduce the use of analgesics and to improve
      quality of life and functional status, thus permit many patients to resume work.
      Many patients told about fair therapeutic effects and the occurrence of mild side
      effects. Thus, SCS is an accessible alternative to traditional therapy. It is the
      treatment of choice in drug-resistant FBSS patients where recurrent neuropathic
      pin persists after surgery and analgesics are no longer effective.

PMID- 17526256
TI  - [Towards the computational three-dimensional histology. Application of computer
      models to the reconstruction of the three-dimensional structure of the biological
      tissue with the sensory cochlear acoustic epithelium in birds as an example].
AB  - This article presents new efficient method of 3-D structure reconstruction of
      epithelia. In contrast to existing empirical approaches, this method is based on
      the use of the families of topological and geometrical models of tissue
      structure, obtained from the axiomatic theory of biological tissue structure,
      with the database of model sections obtained by computer simulation. This
      methodology involves comparison of tissue sections obtained with those taken from
      the database of theoretically predicted models and the selection of the model,
      the sections of which best fit the real ones. This approach significantly reduces
      the amount of necessary tissue sections and eliminates the need for their precise
      superposition. As a result, new method improves resolution and and the efficiency
      of the studies of the spatial organization of epithelia, at the same time
      simplifying them. This approach is oriented primarily on examination of tissue
      topology as the most important aspect of its histoarchitectonics. Application of
      the models also facilitates the evaluation of geometrical properties of the
      tissue and even allows to predict their transformations, thus creating the real
      prerequisite for transition to the 3-D histology.

PMID- 17526257
TI  - [Lymphatic system and its significance in immune processes].
AB  - Up to 80-90th of XX century, lymphatic system was considered as a part of
      vascular system, performing the functions of drainage of tissue fluid from the
      organs, in addition to the venous system. In the second half of XX century,
      detailed research of the organs of lymphatic system, and of lymph nodes in
      particular, lead to the understanding of a defensive role of this system, which
      participated in the elimination of foreign (potentially dangerous) particles-
      fragments of dead cells and other tissue elements. Tissue fluid containing these
      substances, is absorbed into lymphatic capillaries (where it gains the name of
      lymph), flows through the lymphatic vessels to the lymph nodes, which serve as
      lymph biological filters. In the lymph nodes, the foreign particles are detained
      on the fibers of the reticular meshwork, where they are recognized by lymphocytes
      and are eliminated with the help of macrophages. After passage through the lymph
      nodes, cleared lymph flows into the blood through lymphatic ducts and trunks,
      which are continuous with the large veins in the lower regions of the neck. Thus,
      the lymph nodes, that are the organs of immune system, which are formed by
      lymphoid tissue and possess special structures for the clearance of lymph (tissue
      fluid), are, at the same time, the organs of lymphatic system. Lymphatic
      capillaries and vessels provide the transport of the lymph (tissue fluid) to the
      lymph nodes and conduct the lymph to the blood.

PMID- 17526258
TI  - [Ischemic damage-induced nestin synthesis in the rat brain cells].
AB  - Nestin, an intermediate filament protein, is known to be expressed in the
      proliferating and provisional cells of the developing mammalian brain and is lost
      during differentiation. The aim of the present study was to determine the
      morphological type and localization areas of the rat brain cells exhibiting the
      ability to synthesize nestin after a short-term global ischemia of the brain.
      Induction of nestin synthesis after a short-term ischemia was found within the
      injured brain areas in astrocytes, which exhibited structural features atypical
      for these cells in mature brain and maintained them for a long time, and in the
      morphologically undifferentiated cells of subventricular zone, which were able to
      proliferate. However, acquisition by astrocytes of some phenotypic properties of
      immature glial cell does not by itself support the view that they may transform
      into neural stem cells.

PMID- 17526259
TI  - [Remote consequences of prenatal exposure to lead on the brain development in
      rats].
AB  - Administration of a single dose of lead nitrate (200 mg/kg) to pregnant rats (Day
      18 of gestation) resulted in the appearance of destructive brain changes in their
      offspring on postnatal Day 40, including the cysts, foci of glial cell
      proliferation, pyknosis of neurons, decrease of NADH- and NADPH-diaphorase
      activity in neocortical and hippocampal neurons. The reduction of both neuronal
      density in the cortex and cortical thickness was also demonstrated. The intensity
      of free radical oxidation in the cortex was increased 3-fold, while the
      concentration of lipid hydroperoxides was increased 3.9 times, and the resistance
      to peroxidation was decreased by a factor of 3, which is indicative of oxidative
      stress. Possible mechanisms of the pathological changes development are
      discussed.

PMID- 17526260
TI  - [Changes of the goldfish Mauthner neuron ultrastructure and function under the
      influence of 3,4-dihydro-2(1H)-pyrimidinethione].
AB  - The effects of pyrimidine derivative 3,4-dihydro-2(1H)-pyrimidinethione, (DPT)
      used as a test-system for detection of tumor growth, on the goldfish Mauthner
      neurons (MN) ultrastructure and function, as manifested in behavioral changes,
      were studied. The results of investigations demonstrated that an application of
      DPT on MN had the effects similar to those of dopamine application, as
      established earlier, causing the enhancement of MN resistance to fatigue
      stimulation, accompanied by an increase of the dimensions of the actin containing
      desmosome-like afferent admembranous synaptic contacts, and formation of the
      cytoplasmic bundles of actin stress-fibers. Similarity of morpho-functional
      changes of MN, induced by DPT, an artificial chemical substance, which has no
      receptors on the neuronal membrane, and by natural neurotransmitter dopamine,
      allows us to suggest possible trophic stabilizing and polymerizing effects of
      both substances on cytoskeletal actin due to their direct penetration into
      postsynaptic neuron.

PMID- 17526261
TI  - [Thin branches of the human trigeminal ganglion].
AB  - Thin branches of human trigeminal ganglion were studied in material obtained
      during the autopsy of 78 corpses of people aged 23-69 years, using the technique
      of macromicroprepation and total clearing in glycerol following impregnation of
      nerve fibres with silver nitrate after K. Christensen or staining with Schiff
      reagent according to M.G. Shubich and A.G. Khodos, and on serial histotopograms,
      made in sagittal plane, from a material taken from 15 corpses of the people of
      the same age which was also impregnated after K. Christensen. Four histotopograms
      were used for the reconstruction of thin nerves. It was established, that
      trigeminal ganglion directly gave off many branches (more numerous on its outer
      surface as compared to the deep one), with diameters varying from 50 up to 150
      microm. These branches participate in the innervation of the walls of trigeminal
      cavity. No connecting branches of trigeminal ganglion with plexus caroticus
      internus, n. petrosus major or what or any other nerve were detected.

PMID- 17526262
TI  - [Participation of N-cholinergic synapses in the regulation of RNA metabolism of
      sympathetic neurons and satellite glial cells].
AB  - Cytoplasmic rRNA content in neuronal and in satellite glial cells of cervical
      sympathetic ganglion was defined using photographic cytophotometry during the
      pharmacological blockade of N-cholinergic (N-CE) synapses, induced by the
      injection of N-cholinolytic drug dimecoline (10, 30 and 50 mg/kg subcutaneously),
      as well as during the period of blockade gradual resolution and termination (1-11
      hours after treatment with cholinolytic drug). The partial blockade and average
      intensity blockade induced coordinated oscillations of rRNA content in both types
      of cells. The coordination of these changes was violated during the complete
      blockade. Analysis of the results obtained suggested that N-CE synaptic processes
      directly modulated quantitative changes of rRNA in neuronal cytoplasm could be a
      factor synchronizing the metabolism of neuronal and glial rRNA in a sympathetic
      ganglion.

PMID- 17526263
TI  - [Polypoid cushions of arterial vessels and their role in control of regional
      blood circulation].
AB  - This work presents the results of studies of polypoid cushions (PC). For
      elucidation of their structure, morphogenesis and functions, a complex of
      histological, histochemical, morphometric and experimental methods was used. It
      was demonstrated that PC could be detected in the arteries of heart, lungs,
      kidneys, brain and the organs of digestive tract in humans and some animals
      species except the vessells of the minor circle. PC were found at different
      levels of vascular bed with the exception of microcirculatory vessels. They were
      situated in places of arterial branching and sometimes were combined with intimal
      musculature and musculo-elastic sphincters. Three types of PC were distinguished,
      which differed in their histological structure. It was shown that the number of
      PC increased significantly in the cases of circulation disturbances, indicating
      the importance of hemodynamic factor in their development. The functional role of
      these structures might be associated with the regulation of regional blood
      circulation by blocking blood flow and its redistribution within the vascular bed
      in accordance with the requirements of the organ at a particular moment.

PMID- 17526264
TI  - [Comparative morphofunctional characteristic of the thyroid gland under
      conditions of dynamic and static physical loads].
AB  - The changes of thyroid follicular endocrinocytes and elements of microcirculatory
      bed were studied in 102 albino outbred malerats subjected to dynamic and static
      physical loads using the complex of methods of light microscopic morphometry and
      statistical data processing with the application of correlation analysis. The
      results of the study demonstrated that the general peculiarity of the load effect
      was its phase character with a minimum of thyroid activity at day 10 of
      experiment. Changes during dynamic load were found to appear later; with the
      peaks of indexes of thyrocyte hormone production activity at days 5 and 40, these
      were accompanied by the congestion of veins and arteries. During the static load,
      changes appeared earlier; peaks of activity were detected at days 3 and 20, and
      were accompanied by plethora of veins and emptiness of arterial lumen. The
      activity of thyroid follicular endocrinocytes was reduced at days 5 and 30; this
      was accompanied by their desquamation, plasmorrhagia and expansion of
      interlobular spaces.

PMID- 17526265
TI  - [Topografic anatomy of human liver in the early fetal period].
AB  - This investigation was aimed at the evaluation of holotopy, skeletotopy and
      sintopy of human liver in early fetal period. In 60 human fetuses aged 16-24
      weeks, a quantitative characteristic of liver topography was obtained using a
      modification of N.I. Pirogov method and multiplane histitopograms with the
      application of multidimensional coordinate system. Fetal liver sintopy was
      described in sections performed in different planes and its peculiarities in the
      period studied was emphasized. As the standard sections to be used for the
      ultrasonographic and magnetic resonance diagnostics of fetal liver, authors
      recommend the horizontal sections, made at the level of IX-XII thoracic
      vertebrae.

PMID- 17526266
TI  - [Morphometric characteristics of human colon wall as anatomic basis for
      microsurgical anastomoses].
AB  - This article describes the morphometric characteristics and some peculiarities of
      microsurgical anatomy of human colon wall. The thickness of colon wall varied
      from 495 to 3501 microm in the areas between teniae and from 1103 to 4007 microm
      in the areas of teniae, the average values were equal to 1693+93.3 and 2602+85
      microm, respectively. The width of teniae was 3.5-10.3 mm (6.2+0.3 mm on the
      average). The thickness of tunica muscularis along the colon prevailed over the
      thickness of other tunics and increased caudally, while the thickness of
      submucosa diminished. Marked variability and small thickness of both the colon
      wall and its layers, differences of these characteristics in the areas of teniae
      musculares and between them support the expediency of the application of
      microsurgical operative technique in the operations performed on the colon.

PMID- 17526267
TI  - [Age-related changes in glycoprotein composition in human bulbourethral glands].
AB  - Bulbourethral gland glycoprotein (GP) composition was studied histochemically in
      men of different age groups (varying from neonatal period up to 90 years). No
      less than 5 cases were examined for each age group. In children and juveniles,
      neutral GP prevailed in the glandular cells, the proportion of neutral GP
      gradually decreasing with puberty. In youths and in men of mature age, acid GP
      became the predominant component of glandular secretion. In elderly and senescent
      men the ratio of acid and neutral GP again was found to change in favor of the
      latter. In all the age groups, acid GP were represented mainly by sialomucins,
      both sialidase-labile and sialidase-resistant. In the glands of men aged 17 years
      and older, sulphomucins were also detected; the intensity of their synthesis
      increased from the youth to the elderly period and decreased in senescent
      persons. Functional significance of different types of GP in the secretion of
      bulbourethral glands is discussed as well as the possible hormonal machanisms of
      their synthesis.

PMID- 17526268
TI  - [Morphological characteristic of labyrinthine zone of rat allantoic placenta
      after exposure to vibration of industrial frequency].
AB  - The labyrinthine zone of allantoic placenta was studied after dosated exposure to
      vibration. The study was carried out in pregnant female Wistar rats (n=68). Rats
      were subjected to short-term vibration from Day 9 to Day 13 and long-term
      vibration from the Day 9 to Day 18 of pregnancy (taking into account
      embryogenesis periodization and the development period of extraembryonic organs).
      Vibration table with fixed parameters (frequency of 32 Hz and acceleration of 50
      m/s2) was used. Placental and fetal mass were measured, labyrinthine zone
      components were evaluated using the morphometric methods, while labyrinthine cord
      and fetal vessels along Duval's sinus were studied ultrastructurally. Labyrinth
      was analyzed from the point of view of rapprochement of maternal and fetal
      bloodstreams. It was found that the exposure to vibration together with the
      development of compensatory adaptive mechanisms led to chronic placental
      insufficiency. Experimental group with short-term vibration exposure (Days 9-13)
      is of particular interest since chronic placental insufficiency in this group
      should be considered as decompensated.

PMID- 17526269
TI  - [Stereological probing and its use in modern research].
AB  - Stereological methods are widely used in modern research. An essence of the
      stereological analysis is to obtain the information on geometrical properties of
      three-dimensional (3D) objects by their representations of restricted
      dimensionality, i.e., by stereological probing profiles. A typology of
      stereological probing variants is briefly presented. An essence and peculiarities
      of practical application of such useful probes as arbitrary (AUR), isotropic
      (IUR), vertical (VUR) uniform random probes of various dimensionality (0D, 1D,
      2D...), PSI (point sampled intercept), disector, orthogonal triplet, and
      spherical probe, are also examined. The stereological probing variants are
      illustrated with examples taken from recent research. The materials presented can
      be employed in further investigations in biomedicine.

PMID- 17526270
TI  - [New fixative for the biological material].
AB  - New non-toxic fixative for biological material is patented, that is based on
      aqueous solutions solutions of bivalent copper cations. Optimal molarity of
      fixative solution (0.2 M) was established experimentally. The method proposed is
      selective in demonstration of tissue structures using Bielschowsky-Gros
      impregnation of material by silver nitrate.

PMID- 17526271
TI  - [Innervation of the brain: what is innervated by what].
AB  - In the pia mater, brain substance and ependyma, peripheral nerves with sensory
      and effector axons and two types of neurons are located: (1) afferent
      pseudounipolar and bipolar cells and (2) efferent vegetative Dogiel type I
      neurons. Together, these nerves and neurons form the intramedullary part of the
      autonomous nervous system, innervating blood vessels, ependyma and perivascular
      connective tissue.

PMID- 17526272
TI  - [Nestin in the cells of the central nervous system].
AB  - This review describes the most recent data on an intermediate filament protein
      nestin, which is regarded by most of the authors as a possible neural
      stem/progenitor cells marker. Several structure-functional characteristics of
      nestin, its occurrence in different cell types at various stages of ontogenesis
      in physiological and pathological conditions are reviewed.

PMID- 17526273
TI  - [Olympiade in histology, cytology and embryology as a form of self-dependent work
      of the students (methodology, problems, and perspectives)].

PMID- 17526274
TI  - [Documents for the history of biomedicine: the archives of the Section of History
      of Medicine of the University of Rome "La Sapienza"].
AB  - Scientific archives for biomedicine have only recently been brought to the
      attention of the scholarly world. The archives conserved in the Section have
      different origins, only loosely related to the University of Rome; together they
      fully illustrate the achievements and shortcomings of biological and medical
      research in Italy from the late 19th century to the present.

PMID- 17526275
TI  - [Archives for the history of malaria].
AB  - Archives for the history of malaria and malariology in Italy have been
      'rediscovered' in the recent past. The Sezione di Storia della Medicina at Rome
      University conserves many different personal and institutional archives closely
      or loosely related to this topic. Many of them had been originally gathered and
      kept at the Istituto di Igiene at Rome University. Among them the Fondo Casini,
      of the 20th century, documenting the activity of public institutions such as the
      Societa per gli Studi della Malaria and the Scuola Superiore di Malariologia;
      archives of the end of the 19th and beginning of the 20th century, such as the
      Fondo Bignami, Celli; and many others.

PMID- 17526276
TI  - [Malariology offprints in the Bignami archive].
AB  - The offprint collection in the Bignami archive dates from 1865 to 1972. It
      consists of 301 offprints, published in various Western countries, focusing on
      malaria and its eradication. The offprints can be classified by subject: on the
      zoology of parasites, on malarial infection, on the course and treatment of
      malarial fever, on pharmacology. Besides providing a sample of the state of the
      art on malariology in the period, they offer evidence concerning the network and
      activities of malariologists in Italy and abroad.

PMID- 17526277
TI  - [Antimalarial strategies in Italy: scientific conflicts, institutional policies].
AB  - The historiography of malaria in Italy--from the discoveries of the parasite and
      its specific mosquito vector to the eradication of the plasmodia--has
      characterized the evolution of Italian malariology and antimalarial strategies as
      a rationally planned enterprise. The received view is that the essential
      scientific contributions and the effective approaches which ultimately allowed
      the defeat of the disease were produced thanks to the unitary effort of an
      efficient and influential community of investigators. Even though the outstanding
      and international standard of Italian malariologists individually taken cannot be
      downplayed, a more thorough exploitation of archival sources shows that the
      history of the Italian malariological community was also characterized by
      theoretical, academic and personal rivalries, influencing the evolution of
      malariology and the institutional debate on antimalarial strategies. The aim of
      this paper is to examine the reasons and the implications--in different periods
      and institutional dimensions of the antimalarial activitie--of personal and
      institutional disputes within two generations of Italian malariologists. The
      reconstruction of the origins and of the content of persistent scientific and
      institutional controversies within the Italian malariological community does not
      diminish the value of the Italian experience in the field of malariology and the
      antimalarial activities. On the contrary, it contributes to a less
      triumphalistic, but more realistic and dynamic view the conquest of Italian
      malaria.

PMID- 17526278
TI  - [Vittorio Erspamer (1909-1999)].
AB  - Vittorio Erspamer's scientific achievements are highlighted by illustrating his
      long-life commitment to research and to truth, as well as his untiring rhythm of
      work, both in Italy and abroad--in the scientific expeditions organized to gather
      amphibians all around the world. His life and career are set against the
      background of Italian political and cultural life in the Novecento.

PMID- 17526279
TI  - [The Erspamer archive].
AB  - After graduating from Pavia University in 1935, Vittorio Erspamer (1909-1999)
      worked in Germany and held chairs in Pharmacology at Bari, Pavia and Rome
      universities. One of the first researchers to take an interest in
      neurotransmitters, he isolated enteramine (subsequently named serotonine). He
      also isolated, in amphibians and mollusks, peptides acting on muscle cells and
      receptors involved in pain-regulatory mechanisms. The archive contains his
      laboratory notes, as well as his malacology and amphibian skins collection.

PMID- 17526280
TI  - [The Montalenti archive].
AB  - The archival fund by Giuseppe Montalenti, the distinguished Italian genetist and
      biologist, comprehends correspondence--both personal and scientific--, papers on
      his activity as a collaborator to the Enciclopedia Treccani, documentation on
      Montalenti's engagement in the politics of science in Italy and abroad in the
      1950s-60s, a collection of offprints and books. A large part of the archive
      refers to the activities of the IUSB (International Union of Biological
      Sciences).

PMID- 17526281
TI  - [Genetics and international cooperation. Giuseppe Montalenti and modern biology].
AB  - Giuseppe Montalenti (1904-1991) belongs to the generation of scientists that-
      through scientific and political efforts--have contributed to the rebuilding of
      Italian and European science after WWII. In this essay I will briefly encompass
      his contribution to the science of Genetics as a researcher, as an academic and
      as a science administrator, especially focusing on his valuable contributions to
      the field of Human Population Genetics in the 1950s and 1960s and on his role in
      the promotion of projects of international cooperation (viz. the International
      Biological Program of the ICSU, 1965-1974).

PMID- 17526282
TI  - [Montalenti and evolutionism].
AB  - The paper highlights the role played by Giuseppe Montalenti in the dissemination
      of evolutionism in Italy in the 20th century, from the Thirties to the Seventies.
      Through a shrewd use of bibliographic policies--translations, introductions to
      Darwin's and Darwininian works--Montalenti succeeded in popularizing
      evolutionism, as well as a broader notion of biology, in the comparatively
      backward cultural and scientific Novecento Italian scene.

PMID- 17526283
TI  - [The Buzzati Traverso archive].
AB  - The life and activity of Adriano Buzzati-Traverso are significantly linked to the
      birth and development of genetics in Italy, as well as to the achievements and
      the shortcomings of the creation of a 'modern' notion and policy of science in
      our country. His archive sheds light on public and private aspects of his
      activity, especially the creation of important research centers.

PMID- 17526284
TI  - [Biology and utopia. Adriano Buzzati Traverso and Italian science].
AB  - The paper aims at reconstructing the scientific career of Adriano Buzzati
      Traverso, a prominent character in Italian biology after the Second World War. In
      the Fifties and the Sixties, he was able to introduce the new molecular
      approaches in life sciences. A great scientific manager, much ahead of his times
      (at least in Italy), he successfully organized the first postgraduate courses of
      genetics and molecular biology in Pavia, and later created the International
      Laboratory of Genetics and Biophysics in Naples. Between 1962 and 1969, this
      institution gained the greatest respect in the scientific community, but the
      political turmoil in 1969 abruptly ended this fascinating attempt to modernize
      Italian science. Buzzati-Traverso's personal archive allows us to reconstruct the
      detailed history of his scientific enterprises, focusing particularly on the hard
      struggle to modernize management and policies of Italian science.

PMID- 17526285
TI  - [The Bianco and Silvestroni archive].
AB  - The Bianco and Silvestroni archive contains documents referring to the scientific
      and medico-social activity of the two researchers. Documents illustrate the aims
      and methods of campaigns directed to the control of thalassemia in Italy,
      obtained through the creation of a specific institution and the involvement of
      schools and families. A second group of documents refers to the scientific
      activity of the two scientists in the field of hematology and genetics.

PMID- 17526286
TI  - [The problem of characterization of thalassemia intermedia in Italian medical
      research].
AB  - The paper reconstructs the investigations and the debates on thalassemia
      intermedia in Italy from 1925 to the end of the 1940s. It examines particularly
      the contribution of the studies of Ezio Silvestroni and Ida Bianco to the
      identification of clinical features and etiological bases of thalassemia
      intermedia and consequently the nature of its relationships with Cooley's
      disease.

PMID- 17526287
TI  - [Prevention of mediterranean anemia in Latium: Ida Bianco archives].
AB  - Mediterranean anemia or beta-thalassemia is a hereditary syndrome characterized
      by a severe defect in haemoglobin production and an altered morphology of red
      blood cells. Homozygous condition for beta-thalassemia is characterized by short
      survival. Heterozygous condition is clinically found in adolescence and is
      characterized by a less aggressive phenotype. Ida Bianco, with her husband Ezio
      Silvestroni, has conducted a long struggle for beta-thalassemia prevention in
      Italy. They were the first to draw up an accurate map of the distribution of
      thalassemia in Italy and to conceive and implement a campaign against this
      genetic disease by the development of annual screening on at-school teenagers and
      pre-marriage prevention. Here we focused on the analysis of Ida Bianco's archives
      concerning screenings conducted on middle-schools in the Latium by the "Centro
      Studi della Microcitemia" of Rome from 1975 up to today. The results of the
      thirty-years prevention work in the Latium will be described.

PMID- 17526288
TI  - [The Istituto di Storia della Medicina archive and video collection].
AB  - The Istituto di Storia della Medicina at Rome University was to a certain extent
      a one-man achievement. Founded by Adalberto Pazzini in 1937, its collections
      comprehended books, objects, as well as photographs, movies, and other didactic
      video. The Istituto was also a center for publications, conferences and meetings.
      The archival sources that document its activity have been re-evaluated and
      restored in recent years, together with the collections housed in the Library and
      in the Museum.

PMID- 17526289
TI  - [Some remarks on Pazzini's book collection].
AB  - The paper describes the private book collection owned by Adalberto Pazzini and
      kept in the Library of the Sezione di Storia della Medicina. Gathered from the
      1930s to the 1970s, the collection allows a reconstruction of the 'state of the
      art' of medical history in this period in Italy. Books were sent and dedicated to
      Pazzini by colleagues, mostly active in Italy and in the Spanish-speaking
      countries; many of them deal with the history of medicine, but some also with
      medicine itself.

PMID- 17526290
TI  - [Adalberto Pazzini and the origins of the Istituto di Storia della Medicina].
AB  - The first part of the paper deals with the Italian tradition of medical history
      in the 1930s, when Adalberto Pazzini became the most successful medical historian
      in Italy. Its second part deals with the founding and renovation (1938 and 1954
      respectively) of the Istituto di Storia della Medicina at Rome University, with a
      description of the innovative--and largely utopian--planning of the Library and
      of the Museum and didactic collections by Pazzini.

PMID- 17526291
TI  - [Pharmaceutical pottery in the Museum of History of Medicine of Rome "La
      Sapienza"].
AB  - Chemist's and pharmaceutical vases are a historical, aesthetic, cultural, often
      careless, patrimony that evokes numerous suggestions. It is not possible to
      distinguish their history from the history of general ceramics in order to
      reconstruct the context in which these manufactured object were made. Even though
      manufacture presents a peculiarity of its own it interlaces with the objects of
      everyday use and with the production designed to any specific and different uses.
      Ceramics is one of the most flourishing art in Italy; a revival of its techniques
      arose just in relation with the 'rebirth' of spices commercial trading in Italy.

PMID- 17526292
TI  - State of the medical historical art versus science.

PMID- 17526293
TI  - Employee participation in physical activity.

PMID- 17526294
TI  - Chronic obstructive pulmonary disease.

PMID- 17526295
TI  - Health At Every Size: a compassionate, effective approach for helping individuals
      with weight-related concerns--Part II.
AB  - The underlying goal of traditional approaches to weight and health is for
      individuals to be smaller (i.e., lose weight). Little evidence exists supporting
      the efficacy of such approaches and concern is mounting that they may be causing
      harm. An effective, compassionate approach to issues of weight and health--Health
      At Every Size (HAES)--acknowledges the naturally existing diversity in body
      shapes and sizes, the ineffectiveness and dangers of dieting for weight loss, the
      importance of relaxed eating in response to internal body clues, and the critical
      contribution of social, emotional, spiritual, and physical factors to health and
      happiness. Occupational health nurses can use the HAES approach at the worksite
      to assist employees with effectively addressing their weight-related concerns.

PMID- 17526296
TI  - Community-acquired methicillin-resistant Staphylococcus aureus: an ever-emerging
      epidemic.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is
      approaching epidemic status, with life-threatening consequences. Prevention of
      MRSA infections can best be achieved by hand hygiene. Antibiotics should be
      chosen on the basis of culture results and sensitivity.

PMID- 17526297
TI  - Disaster preparedness: occupational and environmental health professionals'
      response to Hurricanes Katrina and Rita.
AB  - In disaster-related events such as these, this survey demonstrates clear need for
      improved preparedness efforts and communication strategies to help reduce health
      risks for at-risk populations. The role of occupational health nurses and
      occupational and environmental medicine physicians requires knowledge and skills
      in many areas. This includes not only clinical skills related to illness and
      injury that will occur, but also skills in such areas as surveillance,
      management, community coordination, risk management and risk communication, and
      health protection. The psychological impact of disasters will have far-reaching
      effects resulting in emotional and behavioral changes requiring both immediate
      and long-term interventions. Comprehensive disaster management guidance should be
      in place to assist health care providers and workers in pre-event, event, and
      post-event phases of the disaster.

PMID- 17526298
TI  - Occupational and environmental health nursing in the era of consumer-directed
      health care.
AB  - Consumer-directed health care plans (CDHPs) present an opportunity to control
      health care costs. Health savings accounts (HSAs) and health reimbursement
      arrangements (HRAs) are two different approaches to providing pre-tax funding for
      CDHP enrollees. Each has a significant impact on the nature and business aspects
      of worksite health care. Worksite clinics can provide support via on-site
      education, expanded acute care services, and referral to other health-related
      benefits and resources for all CDHP enrollees. With attention to the type of
      employee health benefits funding support (HSA or HRA), occupational health nurses
      can maximize the effectiveness and value of worksite clinic services for CDHP
      enrollees.

PMID- 17526299
TI  - Carpal tunnel syndrome: an update.

PMID- 17526300
TI  - Compliance is the issue.

PMID- 17526301
TI  - Primary cicatricial alopecia: clinical features and management.
AB  - The primary cicatricial alopecias are an uncommon, complex group of disorders
      that result in permanent destruction of the hair follicle, usually involving
      scalp hair alone. Prompt diagnosis and treatment are needed to help thwart
      continued hair loss and the distress that often accompanies this hair loss.
      Nurses can facilitate the diagnostic and treatment process and, through
      educational and emotionally supportive measures, have a meaningful, positive
      impact on the patient's well being.

PMID- 17526302
TI  - Management of melanoma during pregnancy.
AB  - There is no conclusive evidence that pregnancy adversely affects overall survival
      in patients with melanoma. Clinicians caring for pregnant patients should be as
      suspicious of changes in melanocytic nevi in these patients as they are for
      nonpregnant patients. Treatment of early-stage melanoma is the same irrespective
      of whether or not the patient is pregnant. Chemotherapeutic regimens for
      metastatic disease administered during pregnancy have not demonstrated
      significant efficacy.

PMID- 17526303
TI  - What's your assessment? Kaposi's sarcoma.

PMID- 17526304
TI  - Sporadic and syndromic keratoacanthomas: diagnosis and management.
AB  - Keratoacanthomas are neoplasms of the skin and mucous membranes. Their nature
      continues to fuel controversies about the benign versus malignant nature of these
      tumors. The characteristics of keratoacanthomas (both the sporadic and syndromic
      types), the controversies about the benign versus malignant nature of
      keratoacanthomas, and current treatment options for keratoacanthomas are
      discussed.

PMID- 17526305
TI  - Presenteeism: sick and tired at work.